PMID- 28488478
TI - Student life - How to fix the leaky bucket: investing in nurse education.
AB - Education is key to fixing 'the leaky bucket', where more nurses are leaving the
profession than joining it, says a specialist RCN group.
PMID- 28488477
TI - The fine art of diversion.
AB - What about the NHS?' says Jeremy. 'Things are getting to breaking point, and I
mean breaking point.'
PMID- 28488479
TI - Readers' panel - Will the Nurse First programme improve recruitment?
AB - Our experts consider a hot topic of the day.
PMID- 28488480
TI - Prime minister fails to comment on nurses having to turn to food banks.
AB - Nursing leaders have criticised the prime minister for failing to explicitly say
whether it is wrong that nurses in the UK have to use food banks.
PMID- 28488482
TI - Staff handovers at bedside allow more time for patient care.
AB - Staff in an emergency assessment unit at an NHS hospital have introduced bedside
nurse handovers to promote interaction with patients.
PMID- 28488484
TI - 'Wonderful and courageous nurse' is Patient's Choice.
AB - Joanna O'Toole has won the 2017 Patient's Choice category of the RCNi Nurse
Awards 2017 - the only category to be decided by a vote open to the general
public.
PMID- 28488485
TI - Staff praised for help after stabbing.
AB - Two hospice nurses have been commended for coming to the aid of a woman who was
stabbed in a knife attack.
PMID- 28488486
TI - Letter.
AB - I don't like bedside handovers. You can't say everything in front of the patient
or in front of the other patients, or their relatives, and it would take longer.
At the end of your shift all you want to do is go home on time.
PMID- 28488487
TI - Too much direction.
AB - So NHS England is to employ two more directors of nursing (news, 26 April).
Presumably this will require the employment of at least two more admin staff and
minions. Total cost? About L200,000 a year? Or about six or seven nurses, just
the amount most wards seem to be short of.
PMID- 28488488
TI - The widening gap.
AB - Differences between the employment situation of NHS nurses working in Scotland
and England are becoming ever more pronounced. This was reinforced recently in
the report from the NHS Pay Review Body (RB) on staff pay in Scotland.
PMID- 28488489
TI - Increase in number of senior BME nurses and midwives is great news.
AB - In March, NHS England published the second Workforce Race Equality Standard
(WRES) data analysis report. This analyses the differences in experience of black
and minority ethnic (BME) and white staff in the NHS, across nine WRES
indicators.
PMID- 28488491
TI - The bored room.
AB - Liverpool Heart and Chest Hospital does not charge for TV or wifi (news online, 3
May). It's all free. And patients can use the phone at the nurses' station.
PMID- 28488490
TI - How to attract a male.
AB - In Malcolm Harrison's response (letters, 26 April) to Andrew Haydon's article
'Where are all the male nursing students?' (students, 12 April), he asks why men
aren't being provided with the same support as other minority groups.
PMID- 28488492
TI - It's time for action.
AB - We all need to strike together: Unison and all nursing union members (readers'
panel, 3 May). But, being nurses, the strike would last less than an hour.
PMID- 28488494
TI - Why RCN Nurse of the Year is such an inspiring winner.
AB - Remember the name: Melanie Davies, RCN Nurse of the Year 2017 and a truly
extraordinary woman. She has transformed care for people with learning
disabilities on her ward, driven through changes across her hospital and health
board in south Wales, and inspired others to follow suit across the country.
PMID- 28488495
TI - Profession's finest honoured at awards.
AB - The innovation, talent and skill of the UK's nursing profession was celebrated at
the RCNi Nurse Awards 2017 last week. The winners were announced at a glittering
evening ceremony at the Westminster Park Plaza Hotel in London on 5 May.
PMID- 28488496
TI - Action Research for Nurses McDonnell Peter and McNiff Jean Action Research for
Nurses 192pp L24.99 Sage 9781473919402 1473919401 [Formula: see text].
AB - The two authors of this long-overdue book offer a cogent critique of the current
body of nursing and research knowledge guided by three basic questions: what
constitutes nursing knowledge, how is knowledge acquired and how is this
knowledge put to use?
PMID- 28488497
TI - The Essentials of Nursing Leadership Taylor Ruth and Webster-Henderson Brian The
Essentials of Nursing Leadership 216pp L22.99 Sage Publishing 9781412962025
1412962021 [Formula: see text].
AB - All aspects of leadership are covered in this excellent book. The first part
focuses on theory of leadership, and the second on necessary skills, approaches
and styles.
PMID- 28488498
TI - 'Always be true to your values'.
AB - Helene Donnelly qualified as a nurse in 2002 and became a nurse practitioner in
the emergency department at Stafford Hospital in 2005. After becoming concerned
about poor patient care, she raised more than 100 complaints and was a key
witness at the inquiry into care failings at Mid Staffordshire NHS Foundation
Trust. She took up her current role as ambassador for cultural change at
Staffordshire and Stoke on Trent Partnership NHS Trust in 2013, and was awarded
an OBE for services to the health service the same year.
PMID- 28488499
TI - Nursing shortages: how bad will it get?
AB - The NHS in England has 24,000 vacancies for nurses, leaving many trusts with more
than 200 posts vacant. But the cumulative impact of a number of factors - from an
ageing workforce and pay restraint to Brexit - could make staff shortages a great
deal worse in the near future.
PMID- 28488500
TI - IV cannula site management.
AB - What was the nature of the CPD activity, practice-related feedback and/or event
and/or experience in your practice? The article discussed management of
intravenous (IV) cannula sites, including cannula insertion, care of the device
and potential complications related to cannula use.
PMID- 28488501
TI - Scotland's new mental health strategy.
AB - Essential facts The Scottish Government has unveiled a ten-year mental health
strategy.
PMID- 28488502
TI - Parents may not want children vaccinated against influenza.
AB - Parents who generally support vaccination may doubt the necessity of an influenza
vaccination for their child, research suggests.
PMID- 28488504
TI - Meet the RCN Nurse of the Year 2017.
AB - 'Never again on my ward, in my hospital, on my health board; that's what I
resolved and I felt it in my heart,' says RCN Nurse of the Year 2017 Melanie
Davies. 'I have driven it and made it real. I made a promise to Paul's family
that no other patient or family would experience the care that he sadly
received.'
PMID- 28488503
TI - Pre-surgery fitness programme reduces patients' stay in hospital.
AB - Patients who 'train' their body before undergoing surgery spend less time in
hospital and have reduced medical costs, a US study has found.
PMID- 28488507
TI - How to assist patients with sit-stand transfers.
AB - Rationale and key points This article discusses optimal methods for assisting
patients with sit-stand transfers where moving-and-handling equipment is not
required. The article explains the importance of effective mobility care in
optimising patients' rehabilitation and enhancing their independence. " The term
'assistance' is used in this article to refer to the support nurses can provide
to patients during sit-stand transfers, but excludes manual assistance. Nurses
should attempt various 'hands-off' mobility-enhancing strategies to assist the
patient, such as the use of verbal, visual or light manual cues. " There are
three main considerations when assisting patients with sit-stand transfers:
maintaining the safety of the patient and healthcare staff; optimising the
patient's mobility; and the use of a person-centred approach to care. " It is
important to ensure the correct biomechanics of sit-stand transfers are followed
during these procedures. Reflective activity 'How to' articles can help you
update your practice and ensure it remains evidence-based. Apply this article to
your practice. Reflect on and write a short account of: 1. How you think this
article will change your practice when assisting patients with sit-stand
transfers. 2. How you could use this resource to educate your colleagues about
sit-stand transfers.
PMID- 28488509
TI - Children's nursing film.
AB - A new short film celebrates the unique role of children's nurses, in response to
concern about moves to sideline the specialty.
PMID- 28488508
TI - Use and relevance of bibliometrics for nursing.
AB - A vast and increasing scientific literature is published each year, including
books, journals, research articles and reviews. One approach to determining the
value of an academic publication involves measuring how often other academic
writers or researchers refer to or cite it. This is the essence of bibliometrics.
This article examines how bibliometrics has developed. It describes how analysing
citations provides a measure of the influence of specific articles (individual
article citations), to compare different journals (journal impact factor) and to
examine the output and impact of individual academics (the h-index). Particular
reference is made to nursing. Using citations should not be the only way that the
value of scholarly work is judged, because there are limitations in using this
method. However, bibliometrics provides an important, feasible and systematic
means of reaching judgments about the importance of published works. As a result,
it can be useful for examining the productivity and influence of individuals and
institutions and for comparing different disciplines and journals.
PMID- 28488510
TI - Keep staff safe and well.
AB - When Denise McLaughlin read about a nurse who crashed her car following a 12-hour
night shift with no break, she was inspired to act.
PMID- 28488512
TI - Taking magnesium could prevent bone fractures in middle age.
AB - Magnesium could prevent bone fractures as a leading cause of disability and ill
health among middle-aged to older people, research suggests.
PMID- 28488511
TI - Emergency care and NHS pay on RCN's congress agenda.
AB - The NHS pay cap, the nursing associate role and the crisis in emergency medicine
are among topics for debate at RCN congress.
PMID- 28488513
TI - High or low birth weight may increase risk of liver disease.
AB - Children with a high or low birth weight may be at an increased risk of
developing non-alcoholic fatty liver disease (NAFLD), according to researchers.
PMID- 28488514
TI - What is said by the bed?
AB - We have been doing bedside nurse handovers for years (news online, 2 May) and
it's absolutely what everyone should be doing. How anyone can hand a patient over
to the next shift without actually being in front of them is beyond me.
PMID- 28488515
TI - Sharing their stories helps young people to feel more understood.
AB - My passion for improving mental health services started after a young woman I
knew took her own life. She was part of a theatre group I volunteered for, and
the distress experienced by fellow members prompted me to take action.
PMID- 28488516
TI - Nursing shortages put future of NHS at risk.
AB - When it comes to the future of the health service, pressure on the workforce is
as great a threat, if not greater, than pressure on finances. This was my
argument in evidence to the House of Lords' recent inquiry into the long-term
sustainability of the NHS.
PMID- 28488517
TI - Last chance for nursing course with bursary.
AB - Would-be nurses have a last chance to train on a fully funded course before
bursaries are scrapped in England - if they are ready to start at the end of
June.
PMID- 28488518
TI - Developing, implementing and evaluating a model for an outpatient self-harm
service.
AB - Aim To reduce the incidence of self-harming behaviour and improve well-being and
experience of care for individuals who present regularly to the emergency
department in one hospital following self-harm, by providing outpatient care.
Method This was a 12-month nurse-led practice development project to develop,
implement and evaluate a brief-intervention outpatient service for individuals
who presented to the emergency department following self-harm and who were
identified as being at risk of further self-harm. The service improvement was
informed by an action research process and the principles of appreciative
inquiry. Findings The project provided a short-term outpatient follow-up service,
known as Brief Interventions in Repeat Self Harm (BIRSH), to patients who
presented to the emergency department following self-harm, and who were
considered at risk of further self-harm. The intervention enabled the clinician
to validate the patient's distress and offer them short-term outpatient follow-up
care. The BIRSH sessions were offered to 38 patients. A total of 26 patients
attended one or more BIRSH session, and all of these individuals showed a
reduction in the number of presentations to the emergency department following
self-harm in the six months following the intervention, compared to the six
months before the intervention. Conclusion The BIRSH outpatient service appears
to have been a contributory factor in reducing self-harm for patients who engaged
with the service. The service improvement was informed by an action research
process and the principles of appreciative inquiry, which provided a positive,
focused approach to the practice development project.
PMID- 28488519
TI - Lessons from Denmark.
AB - As part of a recent trip to Denmark, I visited Kolding Sygehus Hospital, where my
friend is the head of midwifery.
PMID- 28488521
TI - Cycling to work lowers risk of premature death by 41.
AB - New study results suggest cycling to work is associated with a 45% lower risk of
developing cancer and a 46% lower risk of heart disease, compared with a non
active commute.
PMID- 28488520
TI - Report predicts 12% drop in nurse numbers by 2020.
AB - England could see a shortfall of 42,000 nurses by 2020, equivalent to 12% of the
workforce, according to a new report.
PMID- 28488522
TI - Helpline for people at end of life should be available across the UK, says nurse.
AB - A nurse whose husband died at home is calling for the end of life helpline she
staffs to be rolled out nationally.
PMID- 28488525
TI - 'Nurse of the year is a champion for patients with learning disabilities'.
AB - In 2009, neglect at a hospital in Wales contributed to the death of our brother
Paul Ridd, who had severe learning disabilities. The ombudsman said the care he
received had been 'dire'.
PMID- 28488524
TI - Should I stay... or should I go?
AB - If you want to move into a new role, you need to be able to sell yourself to
prospective employers, and the first step is knowing what you are capable of.
PMID- 28488526
TI - Preliminary evaluation for Bit1 as a potential biomarker for squamous cell
carcinoma and adenocarcinoma of esophagus.
AB - Mounting evidence has demonstrated that Bit1 has been investigated as an
etiological factor for certain cancers, including esophageal squamous cell
carcinoma reported in our previous study, but data regarding possible roles of
Bit1 in esophageal squamous cell carcinoma and esophageal adenocarcinoma remain
to be elucidated. The purpose of this study was to examine whether Bit1 can be a
novel diagnostic marker for the patients with esophageal squamous cell carcinoma
and esophageal adenocarcinoma. The results revealed that Bit1 level in esophageal
squamous cell carcinoma was significantly higher than that in esophageal
adenocarcinoma tissues ( p < 0.05); notably, Bit1 level in esophageal
adenocarcinoma tissues was lower than that in paired normal tissues but no
difference was found ( p > 0.05). Bit1 expression patterns were completely in
accordance with matrix metalloproteinase 2 and Bcl-2 in esophageal squamous cell
carcinoma and esophageal adenocarcinoma. In addition, Bit1, Bcl-2, and matrix
metalloproteinase 2 expression patterns in different differentiated esophageal
squamous cell carcinoma were higher than those in corresponding normal esophageal
tissues. Bit1 expression in poorly differentiated esophageal squamous cell
carcinoma was significantly higher than that in normal esophageal tissues ( p <
0.05) but not in moderately and well-differentiated esophageal squamous cell
carcinoma. Matrix metalloproteinase 2 expression patterns in poorly and
moderately differentiated esophageal squamous cell carcinoma were significantly
higher than those in corresponding normal esophageal tissues ( p < 0.01) but not
in well-differentiated esophageal squamous cell carcinoma tissue ( p > 0.05). Bcl
2 expression patterns in various differentiated esophageal squamous cell
carcinoma were higher than those in corresponding normal esophageal tissues with
no statistical differences ( p > 0.05). Importantly, Bit1 expression was
positively correlated with both matrix metalloproteinase 2 and Bcl-2 expression
in esophageal squamous cell carcinoma and esophageal adenocarcinoma tissues ( p <
0.05). Collectively, these preliminary data support further investigation of Bit1
as an important diagnostic factor for esophageal squamous cell carcinoma and
esophageal adenocarcinoma.
PMID- 28488527
TI - Clinical value of miR-452-5p expression in lung adenocarcinoma: A retrospective
quantitative real-time polymerase chain reaction study and verification based on
The Cancer Genome Atlas and Gene Expression Omnibus databases.
AB - The role and mechanism of miR-452-5p in lung adenocarcinoma remain unclear. In
this study, we performed a systematic study to investigate the clinical value of
miR-452-5p expression in lung adenocarcinoma. The expression of miR-452-5p in 101
lung adenocarcinoma patients was detected by quantitative real-time polymerase
chain reaction. The Cancer Genome Atlas and Gene Expression Omnibus databases
were joined to verify the expression level of miR-452-5p in lung adenocarcinoma.
Via several online prediction databases and bioinformatics software, pathway and
network analyses of miR-452-5p target genes were performed to explore its
prospective molecular mechanism. The expression of miR-452-5p in lung
adenocarcinoma in house was significantly lower than that in adjacent tissues (p
< 0.001). Additionally, the expression level of miR-452-5p was negatively
correlated with several clinicopathological parameters including the tumor size
(p = 0.014), lymph node metastasis (p = 0.032), and tumor-node-metastasis stage
(p = 0.036). Data from The Cancer Genome Atlas also confirmed the low expression
of miR-452 in lung adenocarcinoma (p < 0.001). Furthermore, reduced expression of
miR-452-5p in lung adenocarcinoma (standard mean deviations = -0.393, 95%
confidence interval: -0.774 to -0.011, p = 0.044) was validated by a meta
analysis. Five hub genes targeted by miR-452-5p, including SMAD family member 4,
SMAD family member 2, cyclin-dependent kinase inhibitor 1B, tyrosine 3
monooxygenase/tryptophan 5-monooxygenase activation protein epsilon, and tyrosine
3-monooxygenase/tryptophan 5-monooxygenase activation protein beta, were
significantly enriched in the cell-cycle pathway. In conclusion, low expression
of miR-452-5p tends to play an essential role in lung adenocarcinoma.
Bioinformatics analysis might be beneficial to reveal the potential mechanism of
miR-452-5p in lung adenocarcinoma.
PMID- 28488528
TI - Future perspectives of circulating tumor DNA in colorectal cancer.
AB - Tumor biopsy is currently the gold standard for diagnosis and in determining cell
signaling pathways involved in the development of treatment resistance. However,
there are major challenges with this technique, including the need for serial
sampling to monitor treatment resistance, which is invasive and also has the
potential for selection bias due to intra-tumoral and inter-tumoral
heterogeneity. These challenges highlight the need for more effective methods for
obtaining Tumor samples. Liquid biopsy analyzes genetic material or tumor cells
shed into the blood from the primary tumor and metastatic sites and consequently
provides a comprehensive, real-time picture of the tumor burden in an individual
patient. Indeed, liquid biopsy has the potential to revolutionize cancer
management. Here, we review recent studies on the potential clinical applications
of liquid biopsy using circulating tumor DNA in colorectal cancer, including
screening, diagnosis, detection of minimal residual disease after surgery,
detection of recurrence, prognosis, predicting treatment response, monitoring
tumor burden or response during treatment, and tracking resistance. We also
discuss recent data demonstrating the utility of detecting KRAS-mutated
circulating tumor DNA, both at diagnosis to determine an appropriate treatment
strategy and during anti-epidermal growth factor receptor therapy to predict
treatment resistance. The future integration of liquid biopsy into clinical
practice is discussed, together with alternative approaches and key questions
that need to be answered in future clinical studies before this technology can be
implemented and used routinely.
PMID- 28488529
TI - ?
PMID- 28488530
TI - ?
PMID- 28488531
TI - ?
PMID- 28488532
TI - ?
PMID- 28488533
TI - ?
PMID- 28488534
TI - ?
PMID- 28488535
TI - ?
PMID- 28488536
TI - ?
PMID- 28488537
TI - ?
PMID- 28488538
TI - ?
PMID- 28488539
TI - ?
PMID- 28488540
TI - ?
PMID- 28488541
TI - MicroRNA-124 suppresses proliferation and glycolysis in non-small cell lung
cancer cells by targeting AKT-GLUT1/HKII.
AB - Non-small cell lung cancer accounts for 85% of all types of lung cancer and is
the leading cause of worldwide cancer-associated mortalities. MiR-124 is
epigenetically silenced in various types of cancer and plays important roles in
tumor development and progression. MiR-124 was also significantly downregulated
in non-small cell lung cancer patients. Glycolysis has been considered as a
feature of cancer cells; hypoxia-inducible factor 1-alpha/beta and Akt are key
enzymes in the regulation of glycolysis and energy metabolism in cancer cells.
However, the role of miR-124 in non-small cell lung cancer cell proliferation,
glycolysis, and energy metabolism remains unknown. In this research, cell
proliferation was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide; furthermore, glucose consumption and lactic acid
production were assessed; adenosine triphosphate content and NAD+/NADH were also
detected. These tests were conducted using the normal non-small cell lung cancer
cell line A549, which was transfected variedly with miR-mimics, miR-124 mimics,
miR-124 inhibitor, pc-DNA3.1(+)-AKT1, and pc-DNA3.1(+)-AKT2 plasmid. Here, we
show that miR-124 overexpression directly decreased cell growth, glucose
consumption, lactate production, and energy metabolism. MiR-124 also negatively
regulates glycolysis rate-limiting enzymes, glucose transporter 1 and hexokinase
II. Our results also showed that miR-124 negatively regulates AKT1 and AKT2 but
no regulatory effect on hypoxia-inducible factor 1-alpha/beta. Overexpression of
AKT reverses the inhibitory effect of miR-124 on cell proliferation and
glycolytic metabolism in non-small cell lung cancer. AKT inhibition blocks miR
124 silencing-induced AKT1/2, glucose transporter 1, hexokinase II activation,
cell proliferation, and glycolytic or energy metabolism changes. In summary, this
study demonstrated that miR-124 is able to inhibit proliferation, glycolysis, and
energy metabolism, potentially by targeting AKT1/2-glucose transporter
1/hexokinase II in non-small cell lung cancer cells.
PMID- 28488542
TI - CXCL11 mediates TWIST1-induced angiogenesis in epithelial ovarian cancer.
AB - To investigate the role of TWIST1 in tumor angiogenesis in epithelial ovarian
cancer and to identify key molecules involved in angiogenesis. TWIST1 small
interfering RNA was transfected into A2780 cells, while a complementary DNA
vector was transfected into non-malignant human ovarian surface epithelial cells
to generate a TWIST1-overexpressing cell line. To evaluate how this affects
angiogenesis, human umbilical vein endothelial cell tube formation assays were
performed using the control and transfected cell lines. An antibody-based
cytokine array was used to identify the molecules involved in TWIST1-mediated
angiogenesis. After knockdown of TWIST1 via transfection of TWIST1 small
interfering RNA into A2780 cells, the number of tubes formed by human umbilical
vein endothelial cells significantly decreased in a tube formation assay. In a
cytokine array, TWIST1 downregulation did not significantly decrease the
secretion of the common pro-angiogenic factor, vascular endothelial growth
factor, but instead inhibited the expression of the CXC chemokine ligand 11,
which was confirmed by both an enzyme-linked immunosorbent assay and western
blotting. In contrast, TWIST1 overexpression resulted in increased secretion of
CXC chemokine ligand 11. Conversely, CXC chemokine ligand 11 downregulation did
not inhibit the expression of TWIST1. Furthermore, the ability of TWIST1
expressing A2780 cells to induce angiogenesis was found to be inhibited after CXC
chemokine ligand 11 knockdown in a tube formation assay. TWIST1 plays an
important role in angiogenesis in epithelial ovarian cancer and is mediated by a
novel pro-angiogenic factor, CXC chemokine ligand 11. Downregulation of CXC
chemokine ligand 11 can inhibit tumor angiogenesis, suggesting that anti-CXC
chemokine ligand 11 therapy may offer an alternative treatment strategy for
TWIST1-positive ovarian cancer.
PMID- 28488543
TI - The transcription factor FOXA1 induces epithelial ovarian cancer tumorigenesis
and progression.
AB - FOXA1 (forkhead box A1), a member of the FOXA transcription factor superfamily,
plays an important role in tumor occurrence and development. However, the
relationship between FOXA1 and ovarian cancer has not been reported. We examined
normal ovarian tissue and ovarian cancer tissue and found increased FOXA1
expression in the cancer tissue. 3-(4,5-Dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide and flow cytometry assays demonstrated that
transfection with small interfering RNA to silence FOXA1 (si-FOXA1) in ovarian
cancer cell lines decreased cell proliferation and induced apoptosis and S-phase
arrest. In addition, si-FOXA1 transfection inhibited cell migration and invasion.
Western blotting showed that si-FOXA1 transfection decreased the levels of YY1
associated protein 1, cyclin-dependent kinase 1, cyclin D1, phosphatidylinositol
3 kinase, E2F transcription factor 1, B-cell lymphoma 2, and vascular endothelial
growth factor A protein. Based on these results, we suggest that FOXA1 plays a
catalytic role in ovarian cancer pathogenesis and development by affecting the
expression of the above-mentioned proteins.
PMID- 28488544
TI - A long non-coding RNA lncRNA-PE promotes invasion and epithelial-mesenchymal
transition in hepatocellular carcinoma through the miR-200a/b-ZEB1 pathway.
AB - Long non-coding RNAs have been revealed to play important roles in the
progression of hepatocellular carcinoma. However, the detailed mechanisms
underlying their activities are not fully understood. Using microarray
technology, a number of long non-coding RNAs were previously identified to be
aberrantly expressed in hepatocellular carcinoma. In this study, one of these
long non-coding RNAs, designated lncRNA-PE (lncRNA promotes epithelial
mesenchymal transition), was further explored to study its expression profile and
function. A cohort of human hepatocellular carcinoma tissue samples combined with
benign controls and established human hepatocellular carcinoma cell lines were
examined for the expression of lncRNA-PE. The biological functions of lncRNA-PE
were examined by wound-healing and Transwell assays, which revealed that lncRNA
PE promotes cell invasion and migration. By detecting the level of epithelial
mesenchymal transition markers, lncRNA-PE was revealed to promote epithelial
mesenchymal transition in hepatocellular carcinoma cells. Further study suggested
that lncRNA-PE downregulated miR-200a/b by repressing the primary transcript
expression, enhanced ZEB1 expression, and promoted epithelial-mesenchymal
transition of hepatocellular carcinoma cells. All these data imply that lncRNA-PE
might play an important role in hepatocellular carcinoma development via the miR
200a/b-ZEB1 pathway.
PMID- 28488545
TI - Determination of BRAF V600E (VE1) protein expression and BRAF gene mutation
status in codon 600 in borderline and low-grade ovarian cancers.
AB - Epithelial ovarian tumors are a group of morphologically and genetically
heterogeneous neoplasms. Based on differences in clinical phenotype and genetic
background, ovarian neoplasms are classified as low-grade and high-grade tumor.
Borderline ovarian tumors represent approximately 10%-20% of all epithelial
ovarian masses. Various histological subtypes of ovarian malignancies differ in
terms of their risk factor profiles, precursor lesions, clinical course, patterns
of spread, molecular genetics, response to conventional chemotherapy, and
prognosis. The most frequent genetic aberrations found in low-grade serous
ovarian carcinomas and serous borderline tumors, as well as in mucinous cancers,
are mutations in BRAF and KRAS genes. The most commonly observed BRAF mutation is
substitution of glutamic acid for valine in codon 600 (V600E) in exon 15. The
primary aim of this study was to determine whether fully integrated, real-time
polymerase chain reaction-based IdyllaTM system may be useful in determination of
BRAF gene mutation status in codon 600 in patients with borderline ovarian tumors
and low-grade ovarian carcinomas. The study included tissue specimens from 42
patients with histopathologically verified ovarian masses, who were operated on
at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University
Collegium Medicum in Bydgoszcz (Poland). Based on histopathological examination
of surgical specimens, 35 lesions were classified as low-grade ovarian
carcinomas, and 7 as borderline ovarian tumors. Specimens with expression of BRAF
V600E (VE1) protein were tested for mutations in codon 600 of the BRAF gene,
using an automated molecular diagnostics platform IdyllaTM. Cytoplasmic
immunoexpression of BRAF V600E (VE1) protein was found in three specimens: serous
superficial papilloma, serous papillary cystadenoma of borderline malignancy, and
partially proliferative serous cystadenoma. All specimens with the expression of
BRAF V600E (VE1) protein were tested positively for BRAF V600E/E2/D mutation. No
statistically significant relationship (p > 0.05) was found between the presence
of BRAF V600E mutation and the probability of 5-year survival. BRAF mutation
testing with a rapid, fully integrated molecular diagnostics system IdyllaTM may
be also a powerful prognostic tool in subjects with newly diagnosed serous
borderline tumors, identifying a subset of patients who are unlikely to progress.
PMID- 28488546
TI - Long non-coding RNA UCA1 can predict tumor lymph node metastasis.
AB - Numerous studies suggested that long non-coding RNA UCA1 was highly expressed and
played critical roles in the development and progression of various cancerous
tissues and cells. However, little is known about the association between UCA1
and tumor lymph node metastasis. In our study, a systematic review was conducted
to evaluate the association between UCA1 expression and tumor lymph node
metastasis and explore whether UCA1 can be a potential molecular marker for
predicting the multiple tumor lymph node metastasis. The meta-analysis result
showed that the number of lymph node metastasis in different tumorous types of
UCA1 high-expression group was significantly higher compared with UCA1 low
expression group (pooled odds ratio = 2.13, 95% confidence interval: 1.60-2.84, p
< 0.05). To verify whether the above result was still valid in specific tumor
type, we conducted a meta-analysis including four articles on colorectal cancer
(pooled odds ratio = 2.07, 95% confidence interval: 1.28-3.34, p < 0.05). Based
on the existing results, it can be explained that the long non-coding RNA UCA1
was significantly associated with lymph node metastasis and both the results
revealed that compared with UCA1 low-expression group, the lymph node metastasis
rate of UCA1 high-expression group was statistically significantly elevated.
Therefore, long non-coding RNA UCA1 has the potential of being a biological
marker for predicting lymph node metastasis.
PMID- 28488547
TI - Stimulatory role of interleukin 10 in CD8+ T cells through STATs in gastric
cancer.
AB - CD8+ T cells are considered to be critical in tumor surveillance and elimination.
Increased CD8+ T cell frequency and function is associated with better prognosis
in cancer patients. Interleukin 10 is a cytokine with controversial roles in CD8+
T cell-mediated anti-tumor immunity. We therefore examined the interleukin 10
expression and consumption in CD8+ T cells harvested from the peripheral blood
and resected tumors of gastric cancer patients of stages II-IV. We found that the
gastric cancer patients presented significantly elevated frequencies of
interleukin 10-expressing cells in both CD4+ and CD8+ T cells compared to healthy
controls. But distinctive from the interleukin 10-expressing CD4+ T cells, which
increased in frequency in advanced cancer, the interleukin 10-expressing CD8+ T
cells did not increase with cancer stage in the peripheral blood and actually
decreased with cancer stage in resected tumor. Interleukin 10 and interleukin 10
receptor expression was also enriched in interferon gamma-expressing activated
CD8+ T cells. Compared to interleukin 10-nonexpressing CD8+ T cells, interleukin
10 receptor-expressing CD8+ T cells secreted significantly elevated interferon
gamma levels. Treatment of anti-CD3/CD28-stimulated, purified CD8+ T cells with
interleukin 10 alone could significantly enhance CD8+ T cell survival, an effect
dependent on interleukin 10 receptor expression. Interleukin 10 also increased
CD8+ T cell proliferation synergistically with interferon gamma but not alone.
Analysis of downstream signal transducer and activator of transcription molecules
showed that interleukin 10 treatment significantly increased the phosphorylation
of signal transducer and activator of transcription 3 and signal transducer and
activator of transcription 1 to lesser extent. Together, these results
demonstrate that interleukin 10 possessed stimulatory roles in activated CD8+ T
cells from gastric cancer patients.
PMID- 28488548
TI - Angiotensinogen (AGT) gene missense polymorphisms (rs699 and rs4762) and diabetic
nephropathy in Caucasians with type 2 diabetes mellitus.
AB - Gene polymorphisms associated with the renin-angiotensin-aldosterone system
(RAAS) have been extensively studied in diabetic nephropathy (DN) patients, due
to therapeutic potential of targeting the RAAS and slowing down the disease
progression. The aim of our study was to examine the association between
angiotensinogen (AGT) gene polymorphisms (rs699 and rs4762) and DN in Caucasians
with type 2 diabetes mellitus (T2DM). A total of 651 unrelated Slovenian
(Caucasian) T2DM patients were tested for AGT rs699 and rs4762 polymorphisms
using a novel fluorescence-based kompetitive allele-specific polymerase chain
reaction (KASPar) assay. A study group consisted of 276 T2DM patients with DN,
while control group included 375 patients without DN but who have had T2DM for
>10 years. For rs699 polymorphism, the frequencies of GG, GA and AA genotypes
were 20.6%, 52.2% and 27.2%, respectively in T2DM patients and 23.4%, 48.1% and
28.5%, respectively in controls. The distributions of GG, GA and AA genotypes for
rs4762 polymorphism were 73.9%, 23.2% and 2.9%, respectively in T2DM patients and
70.4%, 27.5% and 2.1%, respectively in controls. No significant differences in
the allele frequencies were found between T2DM patients and controls for both
polymorphisms. AGT rs699 and rs4762 missense polymorphisms are not associated
with DN in our subset of Slovenian T2DM patients.
PMID- 28488549
TI - Prevalence of F5 1691G>A, F2 20210G>A, and MTHFR 677C>T polymorphisms in Bosnian
women with pregnancy loss.
AB - The relationship between genetic risk factors of thrombophilia and pregnancy loss
(PL) is being discussed. The focus has been on F5 1691G>A, F2 20210G>A, and MTHFR
677C>T polymorphisms that may predispose women to microthrombosis during the
stages of embryo implantation and placentation. Although, the frequencies of
these polymorphisms were reported in different populations, such studies have not
yet been performed in Bosnian population. In this study, we determined the
prevalence of F5 G>A (rs6025), F2 G>A (rs1799963) and MTHFR C>T (rs1801133)
polymorphisms in Bosnian women. A total of 154 women with PL, mean age 33 (+/
5.4) years, were enrolled in the study. As a control group, 154 mothers [mean age
31.4 (+/-6.7) years] with at least one live-born child were included. We used
real-time polymerase chain reaction (PCR) to determine the frequencies of F5 G>A
and F2 G>A genotypes, and PCR-restriction fragment length polymorphism (RFLP) for
analyzing MTHFR C>T genotypes. The frequency of heterozygotes for F5 and F2 was
significantly higher in women with venous thrombosis (VT) compared to women
without VT (p = 0.047 and p = 0.001, respectively). There was no significant
difference in the distribution of MTHFR genotypes and alleles between these two
groups. In addition, we observed no significant differences in the genotype and
allele frequencies between the group with PL and control group, for all
investigated polymorphisms. The allele frequencies for 1691A (F5), 20210A (F2),
and 677T (MTHFR) reported in this study are consistent with the data obtained for
other European countries, however, we were not able to confirm the association
between the three polymorphisms and PL in Bosnian women.
PMID- 28488550
TI - Tumor suppressive function of microRNA-192 in acute lymphoblastic leukemia.
AB - Non-coding RNAs play a critical role in gene regulation in cancer cells. Reduced
expression of microRNA-192 (miR-192) has been detected in many cancers. In this
study, we investigated the role of miR-192 in cell proliferation and cell cycle
control in NALM-6 cell line, a model of acute lymphoblastic leukemia (ALL). Cell
cycle analysis by DNA content using propidium iodide staining and cell apoptosis
analysis using Annexin V assay were carried out. Cell proliferation changes were
monitored using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
assay. In addition, the relative changes in P53, BAX, CASP3, and BCL-2 gene
expression were determined by quantitative reverse transcription PCR.
Overexpression of miR-192 resulted in cell proliferation arrest in ALL cells.
After 72 and 96 hours of transduction, apoptosis was significantly increased in
the cells transduced with miR-192-overexpressing virus compared with control
cells. The expression of P53, BAX, and CASP3 increased after 48 hours of
transduction in miR-192-overexpressing cells, but no change was observed in BCL-2
expression. The G0/S and G1/S ratio changed to 7.5 and 4.5, respectively, in the
cells overexpressing miR-192 compared with controls. The results of our study
suggest, for the first time, tumor suppressive effects of miR-192 in ALL cells.
PMID- 28488551
TI - [Emergency laparotomy in a trauma patient].
AB - - Emergency laparotomy in trauma patients can be part of the resuscitation
process, is based on damage control principles and is therefore fundamentally
different from elective laparotomy, for example in case of malignancies. -
Indications for emergency laparotomy after trauma are based on haemodynamic
instability of the patient and the procedure is focused on restoring the
patient's physiological condition.- Haemodynamic and biochemical parameters are
used to determine the rest of the strategy. In order to optimize the procedure,
the entire treatment team should be practiced in this.- Fewer and fewer surgeons
are carrying out general laparotomies and even fewer are carrying out emergency
laparotomies after trauma.- Knowledge and skills about emergency laparotomy after
trauma are at risk of disappearing because of this, not only for surgeons but
also for other team members.- Increased centralisation, team training, more
cooperation and consultation for specific indications may all contribute to
expertise preservation.
PMID- 28488552
TI - [Should every doctor be allowed to use ultrasound? Dilemmas surrounding broad
application of ultrasound in clinical practice].
AB - Ultrasound is rapidly gaining ground in clinical medicine. This offers distinct
advantages for diagnosis and treatment. This is notably the case when moving
images are created by the treating physician, who can integrate them immediately
with all other clinical information. The downside of a broad application of
ultrasound is an increase in the number of incidental findings and missed
diagnoses. This is amplified by the frequent lack of formal requirements for
training and skills. Storage of ultrasound images may furthermore lead to
verifiable misinterpretations. We are of the opinion that responsible integration
of ultrasound in clinical practice requires clear peer agreements without
sectarian thinking. To illustrate this, we discuss the dilemmas surrounding
increased use of ultrasound from a medicolegal perspective.
PMID- 28488553
TI - [Is dementia preventable through intensive vascular care? The preDIVA trial].
AB - OBJECTIVE: To assess whether intensive vascular care in GP practices can prevent
dementia in a population of community-dwelling older people. METHOD: This
pragmatic cluster-randomised open-label study (ISRCTN29711771) was conducted in
persons aged 70-78 years who were registered with Dutch GP practices. The only
exclusion criteria were a diagnosis of dementia and limited life expectancy.
Practices were randomly assigned to an intervention arm or a control arm.
Participants in the interventional arm underwent a cardiovascular check-up every
4 months for six years by a practice nurse. Primary outcomes were cumulative
incidence of dementia and functional limitations. Main secondary outcomes were
the incidence of cardiovascular disease and mortality. RESULTS: Between June 2006
and March 2009, 116 GP practices (3526 participants) were recruited and randomly
assigned: 63 (1890 participants) to the intervention group and 53 (1636
participants) to the control group. Primary outcome data were obtained for 3454
(98%) participants; median follow-up was 6.7 years. In this period, dementia was
diagnosed in 121/1853 (6.5%) participants in the intervention group and in
112/1601 (7.0%) participants in the control group. This difference was not
significant (hazard ratio 0.92, 95% CI 0.71-1.19). No differences were found with
regard to functional decline, incident cardiovascular disease and mortality.
CONCLUSION: Long-term intensive vascular care for community-dwelling elderly
patients, provided in a primary care setting, does not result in a reduced
incidence of dementia, functional limitations or mortality. There is, however,
possibly an effect in elderly patients with untreated or sub-optimally treated
hypertension; this warrants further research.
PMID- 28488554
TI - [How can life-threatening external blood loss be stopped? Treatment options in
the prehospital phase].
AB - - 3,500 people die of injuries in the Netherlands every year; 40% of the deaths
are attributable to bleeding.- Treatment of patients with life-threatening blood
loss is part of the trauma care continuum: all the way from incident to hospital
treatment.- This article presents an overview of all treatment options for
stopping life-threatening external blood loss, divided in medical assistance
phases. It also makes a distinction between different types of care providers,
based on the presence or absence of their medical skills.
PMID- 28488555
TI - [Syncope; suspect pulmonary embolism, especially in the elderly].
AB - Syncope can be caused by a pulmonary embolism. This applies in particular to
elderly patients admitted with syncope; in the general population, however,
syncope is far more frequently caused by a vasovagal response or orthostatic
hypotension. Syncope can be the symptom of a pulmonary embolism, even in the
absence of any clinical manifestations of this diagnosis; it is, therefore,
important to exclude pulmonary embolism in any syncope patient in the accident
and emergency department by applying the Wells clinical decision rule. GPs should
also be alert to syncope as a possible symptom of pulmonary embolism, and be
alert to breathing rate and signs of venous thrombosis.
PMID- 28488556
TI - [Treating physicians can perform simple ultrasounds; triage ultrasonography
should be reserved for radiologists].
AB - We feel that, in trained hands, point-of-care ultrasonography by non-radiologists
is of value to patient care. However, more extensive ultrasonography, i.e.,
triage ultrasonography, requires a skill set and a clinical environment that can
currently only be provided by radiologists.
PMID- 28488557
TI - [Added value of observational studies in surgery: the hierarchical structure of
study designs requires a more refined approach].
AB - The randomised placebo-controlled trial (RCT) is the gold standard for the
evaluation of medical interventions. Observational studies, on the other hand,
usually do not get much credit. For studies investigating surgical interventions
this does not always seem entirely justified. A more refined approach might be
needed for the often-used hierarchical structure of research designs. Instead of
a strict separation of results from RCTs and other designs, results of the
different designs should rather be regarded as complementary to each other when
evaluating surgical interventions in traumatology.
PMID- 28488558
TI - [Identifying mild traumatic brain injury: clinical signs and consequences].
AB - Identification of patients with mild traumatic brain injury (TBI) is important
since 85,000 patients visit the emergency department with a head trauma annually.
Although most patients recover well, 15-20% of the patients with head trauma
develop persistent symptoms that interfere with resumption of daily activities.
It is particularly important to identify the clinical signs that define mild TBI.
Presence of anterograde amnesia after the injury, for example, is an important
clinical diagnostic sign to establish the diagnosis of TBI. Posttraumatic
emotional distress may increase posttraumatic symptoms. General practitioners
should be aware of the problems in this patient group and identify patients with
mild TBI who are at risk of developing persistent symptoms that limit
participation in society.
PMID- 28488559
TI - [Hip fracture in elderly patients; additional value of a multidisciplinary
approach and concentration of care].
AB - Management of elderly patients with a proximal femoral fracture is an increasing
challenge for the Dutch healthcare system. Proximal femoral fractures in the
elderly have high morbidity and mortality rates. Furthermore, healthcare costs
for this group of patients are rising. Referral, operation and postoperative care
demand efficient collaboration between healthcare professionals. Every step in
this chain of events is crucial for optimal treatment results. Multidisciplinary
orthogeriatric trauma care shows promising results. In addition, high volume care
results in better outcome of geriatric trauma patients.
PMID- 28488560
TI - [The effects of severe and very severe injuries].
AB - - The effects of severe injuries can be charted using the International
Classification of Functioning, Disability and Health (ICF) model and the burden
of disease model, in which the burden of disease is expressed in 'disability
adjusted life years' (DALYs). - Severe accidents cause 10 DALYs per 1000 people,
which is comparable with the burden of disease of mood disorders and lung cancer.
In the Netherlands, severe injury victims are often males aged < 40 years, who
are often injured in road traffic accidents. - The average hospital stay after a
severe injury is one month, after which almost 75% of the patients are discharged
home, while one quarter subsequently stay in rehabilitation facilities for 3-6
months. More than half return to their original employment. - Patients with
thoracic and abdominal injuries recover relatively well, whereas injuries of the
lower extremities, brain and spinal cord give a relatively poor prognosis.
Comorbidity increases the chance of a less good recovery. Older people who
survive an accident recover relatively well.
PMID- 28488561
TI - An Integrative Cognitive Model of Internalized Stigma in Psychosis.
AB - BACKGROUND: Internalized stigma is a significant difficulty for those who
experience psychosis, but it has never been conceptualized using cognitive
theory. AIMS: The aim of this paper is to outline a cognitive model
conceptualizing internalized stigma experienced by people who also experience
psychosis. METHOD: Previous literature is reviewed, critiqued and synthesized to
develop the model. It draws upon previous social cognitive models of internalized
stigma and integrates cognitive behavioural theory and social mentality theory.
RESULTS: This paper identifies key cognitive, behavioural and emotional processes
that contribute to the development and maintenance of internalized stigma, whilst
also recognizing the central importance of cultural context in creating negative
stereotypes of psychosis. Moreover, therapeutic strategies to alleviate
internalized stigma are identified. A case example is explored and a formulation
and brief intervention plan was developed in order to illustrate the model in
practice. CONCLUSION: An integrative cognitive model is presented, which can be
used to develop individualized case formulations, which can guide cognitive
behavioural interventions targeting internalized stigma in those who experience
psychosis. More research is required to examine the efficacy of such
interventions. In addition, it is imperative to continue to research
interventions that create change in stigma at a societal level.
PMID- 28488562
TI - Exploring the health status of older persons in Sub-Saharan Africa.
AB - Sub-Saharan Africa (SSA) has traditionally had a low life expectancy due to the
onslaught of the HIV epidemic, high levels of chronic diseases, injuries,
conflict and undernutrition. Therefore, research into public health concerns of
older persons has largely been overlooked. With a growing population, the roll
out of antiretroviral treatment, and the effects of globalisation, SSA is
experiencing an increase in the number of people over 50 years of age as well as
an increase in the prevalence of non-communicable diseases (NCD). The aim of this
review is to highlight available research on the health status of older persons
in SSA, and to identify the current gaps that warrant further investigation. A
literature search was conducted across multiple databases to identify studies in
SSA on older persons (aged 50 years and older) related to health indicators
including nutritional status, NCD and HIV burden. While it was concluded that
older persons are at an increased risk of poor health, it was also determined
that significant gaps exist in this particular area of research; namely nutrient
deficiency prevalence. Resources should be directed towards identifying the
health concerns of older persons and developing appropriate interventions.
PMID- 28488563
TI - 3-D printing open-source click-MUAC bands for identification of malnutrition.
PMID- 28488566
TI - Expanding the substrates for a bacterial hydrogenlyase reaction.
AB - Escherichia coli produces enzymes dedicated to hydrogen metabolism under
anaerobic conditions. In particular, a formate hydrogenlyase (FHL) enzyme is
responsible for the majority of hydrogen gas produced under fermentative
conditions. FHL comprises a formate dehydrogenase (encoded by fdhF) linked
directly to [NiFe]-hydrogenase-3 (Hyd-3), and formate is the only natural
substrate known for proton reduction by this hydrogenase. In this work, the
possibility of engineering an alternative electron donor for hydrogen production
has been explored. Rational design and genetic engineering led to the
construction of a fusion between Thermotoga maritima ferredoxin (Fd) and Hyd-3.
The Fd-Hyd-3 fusion was found to evolve hydrogen when co-produced with T.
maritima pyruvate :: ferredoxin oxidoreductase (PFOR), which links pyruvate
oxidation to the reduction of ferredoxin. Analysis of the key organic acids
produced during fermentation suggested that the PFOR/Fd-Hyd-3 fusion system
successfully diverted pyruvate onto a new pathway towards hydrogen production.
PMID- 28488568
TI - Life Cycle Energy Analysis of Reclaimed Water Reuse Projects in Beijing.
AB - To illustrate the benefits of water reuse project, the process-based life cycle
analysis (LCA) could be combined with input-output LCA to evaluate the water
reuse project. Energy is the only evaluation parameter used in this study. Life
cycle assessment of all energy inputs (LCEA) is completed mainly by the life
cycle inventory (LCI), taking into account the full life cycle including the
construction, the operation, and the demolition phase of the project. Assessment
of benefit from water reuse during the life cycle should focus on wastewater
discharge reduction and water-saving benefits. The results of LCEA of Beijing
water reuse project built in 2014 in a comprehensive way shows that the benefits
obtained from the reclaimed water reuse far exceed the life cycle energy
consumption. In this paper, the authors apply the LCEA model to estimate the
benefits of reclaimed water reuse projects quantitatively.
PMID- 28488569
TI - Gene Expression in the Liver Remnant Is Significantly Affected by the Size of
Partial Hepatectomy: An Experimental Rat Study.
AB - Extended hepatectomies may result in posthepatectomy liver failure, a condition
with a high mortality. The main purpose of the present study was to investigate
and compare the gene expression profiles in rats subjected to increasing size of
partial hepatectomy (PH). Thirty Wistar rats were subjected to 30%, 70%, or 90%
PH, sham operation, or no operation. Twenty-four hours following resection, liver
tissue was harvested and genome-wide expression analysis was performed. Cluster
analysis revealed two main groupings, one containing the PH(90%) and one
containing the remaining groups [baseline, sham, PH(30%), and PH(70%)].
Categorization of specific affected molecular pathways in the PH(90%) group
revealed a downregulation of cellular homeostatic function degradation and
biosynthesis, whereas proliferation, cell growth, and cellular stress and injury
were upregulated in the PH(90%) group. After PH(90%), the main upregulated
pathways were mTOR and ILK. The main activated upstream regulators were
hepatocyte growth factor and transforming growth factor. With decreasing size of
the future liver remnant, the liver tended to prioritize expression of genes
involved in cell proliferation and differentiation at the expense of genes
involved in metabolism and body homeostasis. This prioritizing may be an
essential molecular explanation for posthepatectomy liver failure.
PMID- 28488570
TI - Synergy Effects of Hydrodynamic Conditions and Surfactant on Sorption Behavior of
Bisphenol A.
AB - The synergy effects of hydrodynamic conditions and cetyl trimethylammonium
bromide (CTAB) on the distribution behavior of bisphenol A (BPA) in sediment have
been investigated using particle entrainment simulator (PES) and water bath
shaker. The results showed that when the concentration of CTAB is below its
critical micelle concentration (CMC), the shear stress has almost no effect on
the equilibrium sorption amount of BPA on sediment, which is mainly related to
the surfactant concentration. The sorption rates in the rapid sorption phase
increased with increasing CTAB content and shear stress. When the concentration
of CTAB exceeded CMC, equilibrium sorption amount and corresponding time of BPA
on sediment both decreased with increasing shear stress, mainly because the
hydrodynamic conditions enhanced the solubilization ability of the surfactant on
BPA. It was also found that the sorption rate constant showed a linear increase
trend with increasing shear stress.
PMID- 28488571
TI - Performance study of a low-cost adsorbent - raw date pits - for removal of azo
dye in aqueous solution.
AB - The feasibility of using natural waste (raw date pits) as a low-cost adsorbent
for the adsorption of an anionic dye (Congo red) from aqueous solution has been
investigated. Adsorption optimized conditions were obtained at low dose 1 g/L,
initial dye concentration 100 mg/L, pH 2, equilibrium contact time 120 min, and
temperature 20 degrees C. The corresponding adsorption capacity was around 70
mg/g and could reach 150 mg/g by increasing the ionic strength of the dye
solution (0.05 M CaCl2). These results are well modeled by Freundlich isotherm
and kinetics study followed by pseudo second-order model. Thermodynamic
parameters indicate that the adsorption process is endothermic and not
spontaneous. The tests of desorption-regeneration showed that the studied
adsorbent has the disadvantage of the loss of efficiency at its reuse but this is
offset by its abundance. Based on these results, it can be used as competitive
material for the removal of dyes.
PMID- 28488572
TI - Acute hypocalcemia following kidney transplantation may depend on the type of
remote parathyroidectomy: a retrospective cohort study?.
AB - BACKGROUND: Secondary hyperparathyroidism is a common complication of chronic
kidney disease. When medical management fails, parathyroidectomy (PTX) is a
treatment option. The two most common types are subtotal PTX and total PTX with
autotransplantation (AT). To date, there is no consensus as to which procedure is
preferable, especially in patients who are candidates for future kidney
transplantation. The aim of this study was to identify if the type of PTX is a
risk factor for acute postrenal transplant (postRTX) hypocalcemia and a concern
for problems with long-term calcium homeostasis. METHODS: Renal transplant
recipients at Rhode Island Hospital from 2005 to 2014 were screened for prior
PTX. Out of 297 participants, 11 patients met the criteria. They were further
divided into subtotal PTX (n = 5) vs. total PTX+AT (n = 6). Immediate
postoperative (14 days) and long-term (1 year) calcium levels were followed and
analyzed. Linear growth models were used to determine the effects of type of
parathyroidectomy (subtotal PTX, total PTX+AT) alone on hypocalcemia over time.
In these models, pretransplant levels of calcium and PTH were included as
covariates. RESULTS: Baseline characteristics showed that prerenal transplant
(preRTX) parathyroid hormone (PTH) levels were lower in total PTX+AT vs. subtotal
PTX (3.5 vs. 247.2 mg/dL, p < 0.005). PreRTX calcium levels were slightly lower
in subtotal PTX (9.5 vs. 8.25 mg/dL, p < 0.01), but were within normal limits for
both groups. No significant differences were noted between total vitamin D levels
and time between PTX and RTX. Within 14 days postRTX, the total PTX+AT group had
lower average calcium levels (5.8 vs 8.8 mg/dL, p < 0.001); however, both groups
had normal and stable calcium levels from 1 month to 1 year after transplant.
This was further supported after adjusting for preRTX levels of calcium and PTH,
showing a significant interaction between treatment and time such that patients
had lower calcium levels if they underwent total PTX+AT vs. subtotal PTX within
14 days postRTX (beta = -0.204, SE = 0.039, p < 0.001) (Figure
1) but not at 1 year postRTX (beta = 0.035, SE = 0.075, p =
0.640). CONCLUSION: This study suggests that total PTX+AT increases the risk for
acute postRTX hypocalcemia but has no effect on long-term calcium homeostasis. We
speculate that the acuity of the hypocalcemia may be compounded by high-dose
glucocorticoids required for induction, in addition to the preoperative
undetectable PTH. Thus, prior to RTX, physicians should take into account the
type of remote PTX. If a patient had a total PTX+AT, then postRTX hypocalcemia is
likely to occur.?.
PMID- 28488584
TI - Clinicopathologic significance and prognostic value of Ki-67 expression in
patients with gastric cancer: a meta-analysis.
AB - BACKGROUND: The prognostic value and clinicopathologic significance of Ki-67
expression in gastric cancer patients was controversial. This meta-analysis was
performed to clarify the prognostic value and clinicopathologic significance of
Ki-67 expression in gastric cancer patients. MATERIALS AND METHODS: Several
electronic databases were searched for eligible studies. The pooled odds ratio
(OR), hazard ratios (HR) and 95% confidence interval(CI) were calculated to
explore the prognostic value and clinicopathologic significance of Ki-67
expression for disease free survival and overall survival. RESULTS: Totally 5600
gastric cancer patients from 29 studies were included in this study. High Ki-67
expression was significantly related with Lauren's classification (OR = 1.70; P =
0.001; 95%CI: 1.40-2.06) and tumor size(OR = 1.54; P = 0.006; 95%CI: 1.14-2.09).
However, high Ki-67 expression was not significantly associated with lymph node
metastasis (OR = 1.37; P = 0.138; 95% CI: 0.90-2.08) , tumor stage (OR = 1.31; P
= 0.296; 95% CI: 0.79-2.16) and tumor differentiation (OR = 1.03; P = 0.839; 95%
CI: 0.78-1.35). The pooled HRs were 1.87(P = 0.001; 95% CI 1.30-2.69) for disease
free survival and 1.23(P = 0.005; 95% CI 1.06-1.42) for overall survival.
CONCLUSIONS: High Ki-67 expression may serve as a predictive biomarker for poor
prognosis in gastric cancer patients. Stratification by Ki-67 expression may be a
consideration for selection of therapeutic regimen and integrated managements.
PMID- 28488588
TI - Leaf-inspired microcontact printing vascular patterns.
AB - The vascularization of tissue grafts is critical for maintaining viability of the
cells within a transplanted graft. A number of strategies are currently being
investigated including very promising microfluidics systems. Here, we explored
the potential for generating a vasculature-patterned endothelial cells that could
be integrated into distinct layers between sheets of primary cells. Bioinspired
from the leaf veins, we generated a reverse mold with a fractal vascular
branching pattern that models the unique spatial arrangement over multiple length
scales that precisely mimic branching vasculature. By coating the reverse mold
with 50 MUg ml-1 of fibronectin and stamping enabled selective adhesion of the
human umbilical vein endothelial cells (HUVECs) to the patterned adhesive matrix,
we show that a vascular-branching pattern can be transferred by microcontact
printing. Moreover, this pattern can be maintained and transferred to a 3D
hydrogel matrix and remains stable for up to 4 d. After 4 d, HUVECs can be
observed migrating and sprouting into Matrigel. These printed vascular branching
patterns, especially after transfer to 3D hydrogels, provide a viable alternative
strategy to the prevascularization of complex tissues.
PMID- 28488589
TI - Quasicrystalline and crystalline types of local protein order in capsids of small
viruses.
AB - Like metal alloys and micellar systems in soft matter, the viral capsid
structures can be of crystalline and quasicrystalline types. We reveal the local
quasicrystalline order of proteins in small spherical viral capsids using their
nets of dodecahedral type. We show that the structure of some of the viral shells
is well described in terms of a chiral pentagonal tiling, whose nodes coincide
with centers of mass of protein molecules. The chiral protein packing found in
these capsids originates from the pentagonal Penrose tiling (PPT), due to a
specific phason reconstruction needed to fit the protein order at the adjacent
dodecahedron faces. Via examples of small spherical viral shells and geminate
capsid of a Maize Streak virus, we discuss the benefits and shortcomings of the
usage of a dodecahedral net in comparison to icosahedral one, which is commonly
applied for the modeling of viral shells with a crystalline local order.
PMID- 28488590
TI - Synaptic transistor with a reversible and analog conductance modulation using a
Pt/HfOx/n-IGZO memcapacitor.
AB - A synaptic transistor emulating the biological synaptic motion is demonstrated
using the memcapacitance characteristics in a Pt/HfOx/n-indium-gallium-zinc-oxide
(IGZO) memcapacitor. First, the metal-oxide-semiconductor (MOS) capacitor with
Pt/HfOx/n-IGZO structure exhibits analog, polarity-dependent, and reversible
memcapacitance in capacitance-voltage (C-V), capacitance-time (C-t), and voltage
pulse measurements. When a positive voltage is applied repeatedly to the Pt
electrode, the accumulation capacitance increases gradually and sequentially. The
depletion capacitance also increases consequently. The capacitances are restored
by repeatedly applying a negative voltage, confirming the reversible
memcapacitance. The analog and reversible memcapacitance emulates the
potentiation and depression synaptic motions. The synaptic thin-film transistor
(TFT) with this memcapacitor also shows the synaptic motion with gradually
increasing drain current by repeatedly applying the positive gate and drain
voltages and reversibly decreasing one by applying the negative voltages,
representing synaptic weight modulation. The reversible and analog conductance
change in the transistor at both the voltage sweep and pulse operations is
obtained through the memcapacitance and threshold voltage shift at the same time.
These results demonstrate the synaptic transistor operations with a MOS
memcapacitor gate stack consisting of Pt/HfOx/n-IGZO.
PMID- 28488591
TI - Red-emission phosphor's brightness deterioration by x-ray and brightness recovery
phenomenon by heating.
AB - There are no feasible real-time and direct skin dosimeters for interventional
radiology. One would be available if there were x-ray phosphors that had no
brightness change caused by x-ray irradiation, but the emission of the Y2O3:Eu,
(Y, Gd, Eu)BO3, and YVO4:Eu phosphors investigated in our previous study was
reduced by x-ray irradiation. We found that the brightness of those phosphors
recovered, and the purpose of this study is to investigate their recovery
phenomena. It is expected that more kinds of phosphors could be used in x-ray
dosimeters if the brightness changes caused by x-rays are elucidated and
prevented. Three kinds of phosphors-Y2O3:Eu, (Y, Gd, Eu)BO3, and YVO4:Eu-were
irradiated by x-rays (2 Gy) to reduce their brightness. After the irradiation,
brightness changes occurring at room temperature and at 80 degrees C were
investigated. The irradiation reduced the brightness of all the phosphors by 5%
10%, but the brightness of each recovered immediately both at room temperature
and at 80 degrees C. The recovery at 80 degrees C was faster than that at room
temperature, and at both temperatures the recovered brightness remained at 95%
98% of the brightness before the x-ray irradiation. The brightness recovery
phenomena of Y2O3:Eu, (Y, Gd, Eu)BO3, and YVO4:Eu phosphors occurring after
brightness deterioration due to x-ray irradiation were found to be more
significant at 80 degrees C than at room temperature. More kinds of phosphors
could be used in x-ray scintillation dosimeters if the reasons for the brightness
changes caused by x-rays were elucidated.
PMID- 28488592
TI - Reduction of interface traps between poly-Si and SiO2 layers through the
dielectric recovery effect during delayed pulse bias stress.
AB - We investigate the interface trap behavior between tunneling oxide and poly-Si
channel layer post erase/write cycling with a delayed pulse by using deep level
transient spectroscopy. For comparison of the defect states depending on the
stress pulses, a Schottky and a metal-oxide semiconductor device were fabricated.
A defect state at about E c -0.51 eV in the Schottky device was measured before
the annealing process. Three-hole trap states with activation energies of E v
+0.28 eV, E v +0.53 eV, and E v +0.76 eV appeared after the post-annealing
process. The electron trap was about E c -0.15 eV after erase/write 3000 cycling
was applied at +/-10 V for 100 ms at 25 degrees C and 85 degrees C. These
defect states may have an effect on the charge loss behavior of the electrons
localized in the charge trap layer at the retention mode of three-dimensional non
volatile memory devices. Dramatically, after the endurance stress was applied
with a delayed pulse of 300 cycling at 85 degrees C for 50.4 h, no interface
traps of the deep level transient spectroscopy spectra appeared. Dielectric
recovery can decrease the density of the interface trap and improve the retention
properties. This may have been caused by the passivation effect on the dangling
bond of the interface traps.
PMID- 28488593
TI - Towards a new dose and dose-rate effectiveness factor (DDREF)? Some comments.
AB - The aim of this article is to offer a broader, mechanism-based, analytical tool
than that used by (Ruhm et al 2016 Ann. ICRP 45 262-79) for the interpretation of
cancer induction relationships. The article explains the limitations of this
broader analytical tool and the implications of its use in view of the
publications by Leuraud et al 2015 (Lancet Haematol. 2 e276-81) and Richardson et
al 2015 (Br. Med. J. 351 h5359). The publication by Ruhm et al 2016 (Ann. ICRP 45
262-79), which is clearly work in progress, reviews the current status of the
dose and dose-rate effectiveness factor (DDREF) as recommended by the ICRP. It
also considers the issues which might influence a reassessment of both the value
of the DDREF as well as its application in radiological protection. In this
article, the problem is approached from a different perspective and starts by
commenting on the limited scientific data used by Ruhm et al 2016 (Ann. ICRP 45
262-79) to develop their analysis which ultimately leads them to use a linear
quadratic dose effect relationship to fit solid cancer mortality data from the
Japanese life span study of atomic bomb survivors. The approach taken here
includes more data on the induction of DNA double strand breaks and, using
experimental data taken from the literature, directly relates the breaks to cell
killing, chromosomal aberrations and somatic mutations. The relationships are
expanded to describe the induction of cancer as arising from radiation induced
cytological damage coupled to cell killing since the cancer mutated cell has to
survive to express its malignant nature. Equations are derived for the induction
of cancer after both acute and chronic exposure to sparsely ionising radiation.
The equations are fitted to the induction of cancer in mice to illustrate a dose
effect relationship over the total dose range. The 'DDREF' derived from the two
equations varies with dose and the DDREF concept is called into question.
Although the equation for acute exposure can be used to analyse atomic bomb
survivor data, the fitting is dominated by the quadratic dose component. Thus,
little useful information can be derived about the linear dose component which is
important for the derivation of low dose rate risk. The ICRP are advised to
derive the risk at low dose rates from epidemiological studies of, for example,
worker populations, together with information from cellular radiation biological
research.
PMID- 28488594
TI - Large scale production and controlled deposition of single HUVEC spheroids for
bioprinting applications.
AB - We present (1) a fast and automated method for large scale production of HUVEC
spheroids based on the hanging drop method and (2) a novel method for well
controlled lateral deposition of single spheroids by drop-on-demand printing.
Large scale spheroid production is achieved via printing 1536 droplets of HUVEC
cell suspension having a volume of 1 MUl each within 3 min at a pitch of 2.3 mm
within an array of 48 * 32 droplets onto a flat substrate. Printing efficiencies
between 97.9% and 100% and plating efficiencies between 87.3% and 100% were
achieved. Harvested spheroids (consisting of approx. 250 HUVECs each) appear
uniform in size and shape. After incubation and harvesting, the spheroids are
deposited individually in user-defined patterns onto hydrogels using an automated
drop-on-demand dispenser setup. Controlled by an image detection algorithm
focusing the dispenser nozzle, droplets containing exactly one spheroid are
printed onto a substrate, while all other droplets are discarded. Using this
approach an array of 6 * 3 HUVEC spheroids with intermediate distances of 500 MUm
embedded in fibrin was generated. Successful progress of spheroid sprouting and
merging of neighboring sprouts was observed during the first 72 h of incubation
indicating a good viability of the deposited spheroids.
PMID- 28488595
TI - Ab initio prediction of the electronic, magnetic and topological properties of
Ln2O3 clusters.
AB - The structural, electronic and magnetic properties of the lanthanide oxide Ln2O3
clusters, where Ln signifies lanthanides from La to Lu, have been calculated
using spin-polarized density functional theory with the B3LYP hybrid functional.
The intensities of ferromagnetic RKKY interaction are found comparable with that
of antiferromagnetic superexchange interaction in Ce2O3 / Pr2O3 / Nd2O3 / Gd2O3 /
Tb2O3 / Tm2O3 clusters, while the other Ln2O3 clusters prefer ferromagnetic
states to antiferromagnetic states in energy, except nonmagnetic La2O3 and Lu2O3
clusters. The theoretical spin magnetic moments, calculated three-dimensional
spin density maps and dipole moments of Ln2O3 clusters suggest that the induced
polarizations of oxygen atoms in Sm2O3, Eu2O3 and Yb2O3 clusters remarkably lead
to the elongated Ln-O bond lengths in these clusters. The partial density of
states of Ln2O3 clusters reveals that Sm3+ /Eu3+ /Yb3+ ions are distinctive from
other Ln3+ ions in that their Ln-4f electrons are strongly hybrid with O-2 p
electrons. The topological analysis of the electron density was also performed
with quantum theory of atoms in molecules, which indicates the ionic Ln-O bonds
have partial covalent characteristics.
PMID- 28488596
TI - The impact of microfluidic mixing of triblock micelleplexes on in vitro / in vivo
gene silencing and intracellular trafficking.
AB - The triblock copolymer polyethylenimine-polycaprolactone-polyethylene glycol (PEI
PCL-PEG) has been shown to spontaneously assemble into nano-sized particulate
carriers capable of complexing with nucleic acids for gene delivery. The
objective of this study was to investigate micelleplex characteristics, their in
vitro and in vivo fate following microfluidic preparation of siRNA nanoparticles
compared to the routinely used batch reactor mixing technique. Herein, PEI-PCL
PEG nanoparticles were prepared with batch reactor or microfluidic mixing
techniques and characterized by various biochemical assays and in cell culture.
Microfluidic nanoparticles showed a reduction of overall particle size as well as
a more uniform size distribution when compared to batch reactor pipette mixing.
Confocal microscopy, flow cytometry and qRT-PCR displayed the subcellular
delivery of the microfluidic formulation and confirmed the ability to achieve
mRNA knockdown. Intratracheal instillation of microfluidic formulation resulted
in a significantly more efficient (p < 0.05) knockdown of GAPDH compared to
treatment with the batch reactor formulation. The use of microfluidic mixing
techniques yields an overall smaller and more uniform PEG-PCL-PEI nanoparticle
that is able to more efficiently deliver siRNA in vivo. This preparation method
may prove to be useful when a scaled up production of well-defined polyplexes is
required.
PMID- 28488597
TI - Electrohydrodynamics of a compound vesicle under an AC electric field.
AB - Compound vesicles are relevant as simplified models for biological cells as well
as in technological applications such as drug delivery. Characterization of these
compound vesicles, especially the inner vesicle, remains a challenge. Similarly
their response to electric field assumes importance in light of biomedical
applications such as electroporation. Fields lower than that required for
electroporation cause electrodeformation in vesicles and can be used to
characterize their mechanical and electrical properties. A theoretical analysis
of the electrohydrodynamics of a compound vesicle with outer vesicle of radius R
o and an inner vesicle of radius [Formula: see text], is presented. A phase
diagram for the compound vesicle is presented and elucidated using detailed plots
of electric fields, free charges and electric stresses. The electrohydrodynamics
of the outer vesicle in a compound vesicle shows a prolate-sphere and prolate
oblate-sphere shape transitions when the conductivity of the annular fluid is
greater than the outer fluid, and vice-versa respectively, akin to single vesicle
electrohydrodynamics reported in the literature. The inner vesicle in contrast
shows sphere-prolate-sphere and sphere-prolate-oblate-sphere transitions when the
inner fluid conductivity is greater and smaller than the annular fluid,
respectively. Equations and methodology are provided to determine the bending
modulus and capacitance of the outer as well as the inner membrane, thereby
providing an easy way to characterize compound vesicles and possibly biological
cells.
PMID- 28488598
TI - The cover page.
PMID- 28488599
TI - Random reflections.
PMID- 28488600
TI - Two founders of Bombay neurosciences: Dr. Ramchandra G. Ginde and Dr. Menino De
Souza.
PMID- 28488601
TI - 1892 and the tribulations of Joseph Babinski.
AB - In the early 1880s, Joseph Babinski was appointed as Chef de Clinique under Jean
Martin Charcot at Salpetriere, Paris, in France. He appeared for the post of
Professeur Agrege, the pinnacle of academic distinction in France in 1892.
Charles Bouchard, the earliest pupil of Charcot, who described the Charcot
Bouchard aneurysm along with his master, was the Chief of the Board of Jury.
Charcot and Bouchard did not see eye to eye in the later period, and when German
See, an external examiner did not join the board of examiners following illness,
Bouchard, instead of seeking the assistance of an alternate examiner, employed
the special right of Vote of Absence. Babinski and all other pupils of Charcot
were unsuccessful, while those of Bouchard, came out with flying colors. An
embittered Babinski, along with some of the other unsuccessful candidates,
appeared before the Ministry of Public Assistance after a protracted legal battle
for nearly 2 years but lost the case. They were even ordered by the court to pay
on behalf of the the successful candidates for the legal battle. Babinski never
sat for the examination again and this is the story of one of the most
ignominious episodes in an examination anywhere.
PMID- 28488602
TI - Endoscopic management of intracranial cysts: Need of the hour.
PMID- 28488603
TI - Role of neuro-endoscopy and fenestration in the management of brain cysts.
PMID- 28488604
TI - Clinical and health policy-related challenges of pediatric spinal cord injuries.
PMID- 28488605
TI - Surgical considerations in the management of pediatric thoracolumbar fractures.
PMID- 28488606
TI - Pediatric thoracolumbar fractures: Salient points in management.
PMID- 28488607
TI - Pediatric thoracolumbar spinal injuries: A rare and unique clinical scenario.
PMID- 28488608
TI - Epilepsy surgery in children.
AB - Approximately 60% of all patients with epilepsy suffer from focal epilepsy
syndromes. In approximately 15% of these patients, the seizures are not
adequately controlled with anticonvulsive drugs, and such patients are potential
candidates for surgical treatment and majority are children. Epilepsy surgery in
children, who have been carefully chosen, can result in either seizure freedom or
a marked (>90%) reduction in seizures in approximately two-third of children with
intractable seizures. In the multimodality presurgical evaluation approach,
sufficient concordance should be established among various independent
investigations, thus identifying the location and extent of the epileptogenic
zone with a high degree of confidence. Early surgery improves the quality of life
and cognitive and developmental outcome of the child. Surgically remediable
epilepsies in children should be identified early and include temporal lobe
epilepsy with focal lesions, lesional extratemporal epilepsies, hemispherical
epilepsies, and gelastic epilepsy with hypothalamic hamartoma, and can be treated
by resective or disconnection surgery. Palliative procedures include corpus
callosotomy and vagal nerve stimulation for children with diffuse and multifocal
epilepsies, who are not candidates for resective surgery. Deep brain stimulation
in patients with epilepsy is still under evaluation. For children with
"surgically remedial epilepsy," surgery should be offered as a procedure of
choice rather than as a treatment of last resort.
PMID- 28488609
TI - Microvascular decompression for hemifacial spasm: A systematic review of vascular
pathology, long term treatment efficacy and safety.
AB - INTRODUCTION: Hemifacial spasm (HS) is a rare disorder caused by the compression
of facial nerve root exit zone (REZ) at the brainstem by a vascular loop.
Microvascular decompression (MVD) is a popular treatment modality for HS.
OBJECTIVE: The purpose of this study was to determine the long-term efficacy and
safety of MVD for HS by assessing the effect of the procedure from the literature
published over the last 25 years. MATERIALS AND METHODS: A systematic data review
from 1992 to 2015 using specific eligibility criteria yielded 27 studies on MVD
for HS, the data of which were pooled and subjected to a meta-analysis. RESULTS:
The pooled odds ratio (OR) revealed by the meta-analysis showed that anterior
inferior cerebellar artery was the most common offending vessel in 37.8% (95%
confidence interval [CI]: 27.8-47.7%) of the patients. Complete resolution of HS
was seen in 88.5% (95% CI: 86.7-90.4%) of the patients after a long-term follow
up. The complication rate was low following MVD, the most common being temporary
facial paresis in 5.9% (95% CI: 4.3-7.5%) of patients. CONCLUSIONS: MVD is a safe
and effective treatment for HS with long-term benefits and a low complication
rate.
PMID- 28488610
TI - Pregabalin and lamotrigine in central poststroke pain: A pilot study.
AB - BACKGROUND: Comparative study of Class I drugs in central poststroke pain (CPSP)
is lacking. OBJECTIVE: To evaluate the safety and efficacy of pregabalin and
lamotrigine in patients with CPSP. SETTING: Tertiary care teaching referral
hospital. METHODS: We included consecutive patients with CPSP having >=50 mm
score on Visual Analog Scale (VAS) and randomized them to receive either oral
pregabalin or oral lamotrigine. Their clinical findings, serum chemistry, and
cranial magnetic resonance imaging findings were noted. The severity of CPSP was
assessed by VAS while the allodynia was assessed on a 0-10 scale. The hospital
anxiety and depression (HAD) score was also recorded. The primary outcome was>
50% reduction in the VAS score while the secondary outcome was> 50% reduction in
the severity of allodynia and improvement in HAD score at 3 months. Adverse
reactions were noted in both the groups. RESULTS: There were 30 patients with
CPSP with a median age of 54.5 years (Male:Female = 36:4). While both pregabalin
(P < 0.0001) and lamotrigine (P < 0.0001) resulted in significant improvement in
the VAS score (63.3% vs. 53.3%), allodynia (66.7% vs. 75%), and HAD score (80%
vs. 81.8%) compared to the baseline, the was no significant intergroup
difference. Lamotrigine had to be withdrawn in three patients due to skin rash.
CONCLUSIONS: Both pregabalin and lamotrigine are equally effective in CPSP, but
significant side effects leading to drug withdrawal occured with lamotrigine
administration.
PMID- 28488611
TI - Deregulation of microRNAs in blood and skeletal muscles of myotonic dystrophy
type 1 patients.
AB - INTRODUCTION: MicroRNAs (miRNAs) are short RNA molecules of approximately 22
nucleotides that function as post-transcriptional regulators of gene expression.
They are expressed in a tissue-specific manner and show different expression
patterns in development and disease; hence, they can potentially act as disease
specific biomarkers. Several miRNAs have been shown to be deregulated in plasma
and skeletal muscles of myotonic dystrophy type 1 (DM1) patients. METHODS: We
evaluated the expression patterns of 11 candidate miRNAs using quantitative real
time PCR in whole blood (n = 10) and muscle biopsy samples (n = 9) of DM1
patients, and compared them to those of normal control samples (whole blood, n =
10; muscle, n = 9). RESULTS: In DM1 whole blood, miRNA-133a, -29b, and -33a were
significantly upregulated, whereas miRNA-1, -133a, and -29c were significantly
downregulated in the skeletal muscles compared to controls. CONCLUSIONS: Our
findings align to those reported in other studies and point towards pathways that
potentially contribute toward pathogenesis in DM1. However, the currently
available data is not sufficient for these miRNAs to be made DM1-specific
biomarkers because they seem to be common to many muscle pathologies. Hence, they
lack specificity, but reinforce the need for further exploration of DM1
biomarkers.
PMID- 28488612
TI - Analysis of mortality and related factors in 2195 adult myasthenia gravis
patients in a 10-year follow-up study.
AB - OBJECTIVE: To analyze the mortality and potential risk factors for death in
myasthenia gravis (MG) patients. MATERIALS AND METHODS: A total of 2195 adult
patients with MG (aged older than 18 years) diagnosed during the period between
2003 and 2013 were followed-up and retrospectively reviewed. RESULTS: During the
10-year follow-up, 129 patients died and the total mortality rate was 5.88%. The
risk factors associated with MG-related deaths were duration of the disease,
occurrence of myasthenic crisis, severity of disease that included the Myasthenia
Gravis Foundation of America (MGFA) grade III and IV at onset, elevation of
acetylcholine receptor antibody (AchR-abs) titers, presence of thymic pathology,
and failure of administrating immunosuppressants (P < 0.05). In addition, the non
MG related factors, including the history of preceding strokes, and the presence
of chronic obstructive pulmonary disease (COPD), diabetes mellitus, atrial
fibrillation, hyperlipidemia, myocardial infarction, and malignant tumors, were
closely linked with death in the MG population (the hazard ratios [HRs] were
3.251, 4.173, 3.738, 3.886, 1.945, 2.177, and 14.7, respectively; P< 0.05).
CONCLUSIONS: The severity of disease at entry, presence of AchRabs, thymic
pathology, and duration of the disease predict a higher risk for death. Systemic
illnesses including stroke, COPD, diabetes mellitus, atrial fibrillation,
hyperlipidemia, myocardial infarction, and malignant tumor, which may also
increase the risk of death, should be carefully monitored and managed.
PMID- 28488613
TI - What kills a myasthenic? Myasthenia or otherwise.
PMID- 28488614
TI - Safety and efficacy of therapeutic membrane plasmapheresis in the treatment of
Guillain-Barre syndrome: A study from a tertiary care hospital from India.
AB - BACKGROUND: Reports on therapeutic plasma exchange (TPE) with the standard
hemodialysis equipment are scarce, particularly from developing countries.
MATERIALS AND METHODS: A retrospective analysis of safety and efficacy of
membrane-based TPE with a standard hemodialysis equipment for the treatment of
severe Guillain-Barre syndrome (GBS) was conducted. RESULTS: A total of 120 TPE
sessions were performed in 31 GBS patients over a period of 51/2 years. Each
patient underwent a mean of 3.8 +/- 1.5 TPE sessions. One (3.2%) patient died.
Thirty (96.8%) patients survived and recovered. At 2 weeks, there was a
significant improvement in the grade of power in both the upper and lower
extremities (P = 0.001) and a significant decrease in the GBS disability grade (P
= 0.001). Twenty four (77.4%) patients were able to walk unaided. Complications
observed were: hypotension in 12 (10%), accelerated hypertension in 3 (2.5%),
chills and rigors in 5 (4.2%), bleeding in 5 (4.2%), and filter clotting in 6
(5%) sessions. One patient experienced an anaphylactoid reaction and 1 patient
survived a cardiorespiratory arrest. Two patients developed aspiration pneumonia
and 1 patient developed catheter site infection. CONCLUSIONS: Membrane-based TPE
can be conveniently delivered with the standard hemodialysis equipment. It is a
safe, effective, and comparatively less expensive treatment option for GBS.
PMID- 28488615
TI - Sensory tricks in primary blepharospasm and idiopathic cervical dystonia.
AB - OBJECTIVE: To study the frequency, types, phenomenology, and effectiveness of
sensory tricks in patients with primary blepharospasm and idiopathic cervical
dystonia. BACKGROUND: Sensory tricks are maneuvers seen in patients with
dystonia, which are used to temporarily reduce the severity of dystonic postures.
In different types of dystonia, the frequency of sensory tricks have been
described to range from 17-89%. MATERIALS AND METHODS: In this cross-sectional
observational study, we analyzed the frequency, types, phenomenology, and
effectiveness of sensory tricks in 20 patients with primary blepharospasm and 20
patients with idiopathic cervical dystonia, respectively. Patients underwent a
clinical examination, and the severity of dystonia was measured using the Burke
Fahn Marsden dystonia rating scale (eyes and neck components).A questionnaire
regarding the sensory tricks was administered to all the patients. RESULTS:
Eighteen patients with blepharospasm and 7 patients with cervical dystonia used
sensory tricks to alleviate their dystonic movements (P < 0.05). The age group of
the patients with cervical dystonia presenting with sensory tricks was
significantly lower than that of those having blepharospasm (P < 0.05). Sensory
tricks, when used, were effective every time in 72.2% of patients with
blepharospasm and in 85.8% of patients with cervical dystonia. However, majority
of the patients with blepharospasm (61.1%) and cervical dystonia (42.9%) had only
partial benefit (<50%) with these maneuvers. CONCLUSIONS: In this study, sensory
tricks were more common in patients with primary blepharospasm than in patients
with idiopathic cervical dystonia.Age of the patients with cervical dystonia was
significantly lesser than those suffering from blepharospasm.We did not find any
correlation between the presence of sensory tricks, the severity of dystonia and
the duration of the disease.Majority of the patients derived benefit with sensory
tricks every time; however, the benefit was only partial.
PMID- 28488616
TI - Sensory tricks in dystonia: Phenomenology and mechanisms.
PMID- 28488617
TI - Do the clinicoradiological outcomes of endoscopic fenestration for intracranial
cysts count on age? An institutional experience.
AB - BACKGROUND: The clinicoradiological outcome of endoscopic fenestration of
intracranial cysts and predictors of an unfavorable outcome, including age, are
under reported in the neurosurgical literature. In this cohort, our experience in
the endoscopic fenestration of intracranial cysts is reviewed. MATERIALS AND
METHODS: Thirty consecutive patients treated with endoscopic fenestration for
intracranial cysts were identified and analyzed. The study population in our
series was followed clinically and radiographically. RESULTS: In this series, the
overall resolution of clinical symptoms such as headache, seizures, and
neurological deficits was 83%, P= 0.0001. The percentage of clinical resolution
after endoscopic intervention was significantly higher (85% vs. 76%, P= 0.001) in
arachnoid cysts compared to other cyst types. The reduction of arachnoid cyst
size was significantly higher in adults with obstructive hydrocephalus compared
to the children group (P = 0.037). In addition, requirement of a cystoperitoneal
shunt placement (P = 0.0001) and its subsequent revision (P = 0.0001) was
significantly lower in adults compared to children. Adults (P = 0.041), presence
of an arachnoid cyst (P = 0.026), female gender (P = 0.016), and presence of
communicative hydrocephalus (P = 0.015) were significant predictors for
improvement in the symptoms of intracranial pressure. Lastly, adults (P = 0.028),
presence of arachnoid cyst (P = 0.046), and presence of communicative
hydrocephalus (P = 0.012) were significant positive predictors for shunt
revision. CONCLUSIONS: This study revealed that endoscopic fenestration is an
effective neurosurgical procedure for the management of intracranial cysts both
in adults and children. Moreover, endoscopic fenestration is more beneficial in
adults and patients with an arachnoid cyst compared to that in children and other
cyst types, respectively.
PMID- 28488618
TI - Pediatric thoracolumbar spinal injuries: The etiology and clinical spectrum of an
uncommon entity in childhood.
AB - BACKGROUND: Pediatric thoracolumbar (TL) spinal injuries are uncommon entities
with an incidence of 5-34% of all pediatric spinal injuries. There is a scarcity
of studies done on the pediatric population in the developing countries like
India. This study aims to review our experience with TL spine injuries in
children over a 12-year period. MATERIALS AND METHODS: We retrospectively
reviewed the epidemiology, risk factors, mechanisms, patterns of injury and
management of pediatric TL injuries in our population. RESULTS: There were 90
children with TL spine injuries comprising 2% of all the spine injuries treated
in our institute. The mean age was 15.9 +/- 3.2 years (range: 2-18 years) with a
male predominance (3:1). The most common mode of injury was fall from height.
64/90 (71.1%) children sustained injury due to fall from height, 18/90 (20%)
children sustained injury following motor vehicle accident and rest of the
children sustained injury due to the fall of a heavy object over the neck. Most
of the patients (27.8%) sustained Grade A injury. Lumbar spine was the most
common spinal level injured (53.3%), and fractures were the most common type of
injury (93.3%). Surgical fixation was performed in 18/90 (20%) children. Follow
up was available for 21 children of which 13 (62%) were ambulant at follow-up.
CONCLUSION: TL injuries are rare and are most common in children older than 10
years and mainly involve the lumbar region. When indicated, surgical fusion of
the involved vertebrae is safe and effective.
PMID- 28488620
TI - Peripheral nerve injuries - A call for better evaluation and preventive measures.
PMID- 28488619
TI - Peripheral nerve injuries: A retrospective survey of 1124 cases.
AB - BACKGROUND: Peripheral nerve injuries (PNIs) remain an important health problem
often leading to severe motor disabilities predominantly in the younger
population. OBJECTIVE: To analyze our experience of clinical and
electrodiagnostic evaluation (EDX) of PNIs over a 26-year period. MATERIALS AND
METHODS: Between 1989 and 2014, 1124 consecutive patients with 1418 PNIs were
referred for clinical as well as EDX evaluation. These PNIs involved upper and
lower limbs as well as the facial nerves. Patients with iatrogenic lesions and
spinal cord/spinal root lesions were excluded from this analysis. Brachial plexus
(BP) injuries with associated or not with root avulsions were considered as one
particular nerve and was include in the study as BP. The etiological categories
of the sustained trauma included vehicular accidents, penetrating injuries,
falls, gunshot wounds, car accidents involving pedestrians, sports injuries, and
miscellaneous injuries. RESULTS: The mean age of our patients was 34.2 years and
most were males (76.7%). Majority (80.9%) of the PNIs were isolated injuries.
Combined lesions most commonly involved the ulnar and median nerves. Upper-limb
PNIs accounted for 72.6% of our patients. The ulnar nerve was injured most often,
either singly or in combination. Vehicular accidents were the most common causes
of injury (46.4%), affecting the brachial BP or the radial, fibular, or sciatic
nerves. Penetrating trauma (23.9%) commonly affected the ulnar and the median
nerves. Falls and gunshot wounds frequently affected the ulnar, radial, and
median nerves. Sports injuries, mostly soccer related, affected predominantly the
fibular nerves. BP injuries were considerably more common in accidents involving
motorcycles than those involving cars (46.1% vs. 17.1%), and root avulsions was
more frequently associated in these cases. CONCLUSIONS: Most PNIs were caused by
vehicular accidents and penetrating trauma, and affected young men. Overall,
ulnar nerve, primary BP, and median nerve PNIs were the most prevalent lesions.
PMID- 28488621
TI - Tumefactive acute disseminated encephalomyelitis.
AB - Tumefactive demyelinating lesions are tumour-like presentations of acute
demyelinating lesions. They have been described with multiple sclerosis only and
not with other varieties of acquired demyelination like acute disseminated
encephalomyelitis (ADEM). The uncertainty about the diagnosis at the onset of the
disease in tumefactive ADEM makes it important that the physicians should be
aware of this entity. Various radiological similarities with more sinister
lesions like central nervous system gliomas or lymphomas may lead to this
confusion. Appropriate supportive treatment with steroids and follow up is
required in these cases to avoid unnecessary interventions.
PMID- 28488622
TI - Family with Ehlers-Danlos syndrome (combined classic and vascular type) with rare
presentation of progressive myopathy and unusual association of severe facial and
trigeminal motor weakness.
AB - We report the clinical, radiological, biochemical, muscle histology, and electron
microscopic features of two members of a family with combined Ehlers-Danlos
syndrome (EDS) [classic and vascular type] and progressive myopathy as the
primary manifestation. A 35-year old lady presented with severe gluteal and thigh
muscle pain and easy fatigability for 5 years. She developed weakness and wasting
of pelvic and pectoral girdles and thighs for 3 years and severe neck flexor and
truncal weakness for 6 months. She had a history of recurrent jaw dislocation,
easy bruising with hyperpigmentation, hyperextensibility of joints, translucent
skin, and papyraceous scars. She had high myopia with astigmatism. She had
wasting of temporalis, masseters, sternocleidomastoids and trapezius. There was
moderate weakness of temporalis, masseters, and facial muscles. Muscle power was
Medical Research Council (MRC) grade 4 at shoulders and arms, and grade 3+ at
pelvis and thighs. Serum homocysteine level was normal, and creatine kinase (CK)
was 275 IU. Two dimensional echocardiogram (2D Echo) showed myxomatous
degeneration of mitral valves. Electromyography (EMG) was suggestive of a
myopathic pattern. Muscle magnetic resonance imaging (MR) revealed severe fatty
infiltration of paraspinal muscles, gluteus maximus and medius, quadriceps,
hamstrings, and gastrocnemius. Electron microscopy showed an occasional distorted
fibril with mild increase in oxytalan fibers and variation in thickness of blood
vessel basement membrane. Her 15-year old daughter had exertion-induced myalgias,
right hemifacial hypoplasia, myopia, hyperextensible joints, hyperelastic skin,
and neck muscle weakness. However, her CK and 2D Echo were normal. This report
presents the rare combination of classic and vascular type of EDS primarily
presenting as muscle weakness and associated with facial and trigeminal motor
weakness.
PMID- 28488623
TI - Endovascular pulmonary artery inflatable balloon-induced hypotension: A novel
technique for clipping giant intracranial aneurysms.
AB - Management of giant intracranial aneurysms presents unique challenges to the
neurosurgical team. Various techniques such as adenosine-induced hypotension,
rapid ventricular pacing, and inducing deep hypothermia are described in the
literature to effect circulatory arrest for the successful obliteration of giant
aneurysms. We describe a novel technique of induced hypotension for clipping a
giant aneurysm by using an inflatable balloon across the main pulmonary artery
with a successful outcome. This technique has not been described earlier in the
literature.
PMID- 28488624
TI - Papillary craniopharyngioma: A clinicopathologic study of a rare entity from a
major tertiary care center in Pakistan.
AB - BACKGROUND: Papillary craniopharyngioma (PCP) are uncommon variants of
craniopharyngiomas (CP), which are benign epithelial neoplasms of the sellar and
suprasellar region. Histologically, PCPs are typically composed of well
differentiated stratified squamous epithelium; however, focal variations are not
uncommon. A distinction from other lesions of the region, despite being difficult
to achieve due to the overlapping radiological and clinical features, is
important for adequate treatment to be administered. OBJECTIVE: Our aim was to
study the clinical and histological features of PCP with emphasis on features
that are helpful in its distinction from other lesions that are similar in
appearance. MATERIALS AND METHODS: We reviewed 13 cases of PCP diagnosed in our
institution between January 2010 and December 2015. RESULTS: The mean age at
presentation was 30.76 years. Two of the patients belonged to the pediatric age
group. Male-to-female ratio was 2.25:1. Suprasellar location (either alone or in
combination with sellar region) was the most common tumor site. Microscopically,
all of the cases showed stratified squamous epithelium with frequent
pseudopapillae formation. Focal adamantinomatous epithelium and columnar
epithelium with variable cilia and goblet cells were seen in 4 (30.7%) cases.
Brain invasion was observed in 3 (23%) cases. Four patients died of their
disease; 2 of the 7 patients with an available follow up, developed recurrences;
and, 5 experienced severe postoperative morbidity. CONCLUSION: Majority of the
PCPs exhibited typical features with minor variations. Knowledge of the
variations in histologic features helps in reaching the correct diagnosis. These
tumors can behave aggressively with a high recurrence rate and decreased overall
survival.
PMID- 28488625
TI - Genetics of pituitary adenomas.
AB - Clinically relevant pituitary tumors presenting with altered hormonal secretion
or mass effect represent a significant proportion of patients in endocrinology
clinics. However, in recent years, these patients are also referred to clinical
genetic services due to possible germline mutations causing syndromic or isolated
pituitary adenomas. While somatic mutations have been identified in GNAS, USB8,
PIK3CA, GPR101 and rarely in RAS, germline mutations have been identified in
MEN1, cyclin dependent kinase inhibitor genes, AIP, DICER1, PRKAR1A, PRKACA, SDH
genes and GPR101. In this review, we present a short overview of pituitary
adenoma classifications, pituitary development and somatic and germline genetic
changes identified in these adenomas.
PMID- 28488626
TI - Surgery for superior hypophyseal artery aneurysms: A new classification and
surgical considerations.
AB - BACKGROUND: Superior hypophyseal artery (SHA) aneurysms form a unique subgroup of
paraclinoid aneurysms having a propensity to grow to a large size in the
suprasellar region resulting in compression of the optic nerve, chiasma, and/or
tract. AIM: A new classification of SHA aneurysms is proposed that helps in
identifying the surgical issues encountered during surgical clipping of these
medially directed aneurysms located at different segments of the medial surface
of the internal carotid artery (ICA). SETTINGS AND DESIGN: This descriptive study
was conducted at a tertiary care university hospital. MATERIAL AND METHODS: In 14
patients operated for a SHA (mean age: 49.43 +/- 11.28 years; presenting either
with subarachnoid hemorrhage (n = 11; 78.57%) or mass effect (n = 3; 21.42%), 4
parameters having a bearing on surgery [a. size: (small <1 cm n = 5, large 1-2.5
cm n = 7, giant >2.5 cm n = 2); b. origin of SHA aneurysmal neck and direction of
its fundus; c. relationship of the aneurysm to important neurovascular
structures; and, d. whether the aneurysms were saccular or fusiform] were used to
divide SHA aneurysms into 7 categories a. Antero-supero-medial (n = 2); b. Antero
infero-medial (n = 1); c. Supero-medial (n = 3); d. Infero-medial (n = 3); e.
Postero-medial (n = 2); f. Fusiform (n = 1); and, g. Giant (n = 2). Modified
Rankin Scale (MRS) score was utilized to assess outcome [favorable: mRS 0-2;
unfavorable: mRS 3-6] at discharge and follow up. RESULTS: Modified Hunt and Hess
grade at admission was 0 = 3; I = 3; II = 3; III = 2; IV = 3 (favorable mRS: 10;
71.42%; unfavorable mRS: 4; 28.57%); and, Fisher grade was I = 3; II = 6; III =
2; IV = 3. Twelve patients required anterior clinoid process drilling/carotid
collar opening to facilitate optic nerve mobilization, for proximal ICA control,
and to assess the proximal part of the neck of aneurysm for aneurysmal clipping
(n = 13) or wrapping (n = 1). Fenestrated clip was applied in 5 patients. In the
supero-medial group (antero-supero-medial, supero-medial, and postero-supero
medial), the aneurysmal fundus was found directly below the ipsilateral optic
apparatus, elevating it; in the postero-supero-medial group, the fundus often lay
in close proximity to A1 artery, Heubner's recurrent artery, ICA bifurcation, or
dorsum sellae. Optic pathway, hypothalamic, and medial lenticulostriate
perforators also required careful separation. Antero-infero-medial SHA aneurysm
was hidden from view, embedded in the anterior wall of sella below tuberculum
sellae. At a median follow-up of 17.5 +/- 26.78 months (range: 8-84 months), 9
(64.28%) patients had a favorable mRS and 5 (35.71%) an unfavorable one.
CONCLUSION: Systematically classifying SHA aneurysms and anticipating the
surgical risk based upon their anatomical variations helps in achieving a good
surgical outcome.
PMID- 28488627
TI - Neurosurgery at the Bombay Hospital.
AB - Neurosurgery at Bombay Hospital started in 1953 when Dr. Ram Ginde joined as the
Honorary Neurosurgeon. Over the years, the Department of Neurosurgery has earned
the reputation of providing contemporary medical services as well as of imparting
excellent training to the neurosurgical residents. Professor S. N. Bhagwati
started the prestigious annual 'Ginde oration' in 1991, that has been given by
several illustrious orators from across the world and has become a precursor of
various medical activities held thereafter. This article retraces the history and
achievements of the Department of Neurosurgery, Bombay Hospital Institute of
Medical Sciences, Mumbai, and also highlights the immense contributions made by
its members in the field of Neurosurgery in India.
PMID- 28488628
TI - A summary of some of the recently published, seminal papers in neuroscience.
PMID- 28488629
TI - Severe hypoglycemia mimicking raised intracranial pressure - A word of caution.
PMID- 28488630
TI - Brainstem infarct as a rare complication of coagulase-negative staphylococcus
meningitis.
PMID- 28488631
TI - Ruptured dissecting aneurysm of the recurrent artery of Heubner: Consideration of
pathological findings.
PMID- 28488632
TI - Ruptured intracranial tuberculous aneurysm, a rare complication of central
nervous system tuberculosis- A report and review of literature.
PMID- 28488633
TI - A report of whole-genome sequencing in neurologic Wilson's disease.
PMID- 28488634
TI - Paroxysmal tonic spasms as an initial manifestation of neuromyelitis optica.
PMID- 28488635
TI - Movement disorders in anti-NMDA receptor encephalitis.
PMID- 28488636
TI - Catathrenia: A rare disorder presenting as daytime sleepiness and headache.
PMID- 28488637
TI - Dengue fever triggering hemiconvulsion hemiplegia epilepsy in a child.
PMID- 28488638
TI - A rare presentation of trigeminal neuralgia in lateral medullary syndrome.
PMID- 28488639
TI - Alpha coma: A report.
PMID- 28488640
TI - A rare case of Marchiafava-Bignami disease: Extracallosal lesions involving
bilateral medipeduncle.
PMID- 28488641
TI - Cerebral venous thrombosis due to pheochromocytoma in a patient with Von Hippel
Lindau mutation.
PMID- 28488642
TI - Post digital subtraction angiography parenchymal contrast staining mimicking the
presence of a hemorrhage.
PMID- 28488643
TI - Primary progressive freezing gait: Report of five cases.
PMID- 28488645
TI - Post-discectomy annular pseudocyst: A rare cause of failed back syndrome.
PMID- 28488644
TI - Medullomyoblastoma: A report of two cases.
PMID- 28488646
TI - Primary intradural cervical spine melanocytoma: A rare tumor and review of
literature.
PMID- 28488647
TI - "Smart click" to the rescue of the patient's eye: Preventing compression on the
globe during surgery in prone position using the selfie mode.
PMID- 28488648
TI - A rare case of an internal acoustic meatal tuberculoma involving the VII-VIII
nerve complex.
PMID- 28488649
TI - Cost effective, technically simpler, and aesthetically promising cranioplasty in
developing countries.
PMID- 28488650
TI - Dorsolumbar spine Epstein Barr virus associated leiomyosarcoma in a human
immunodeficiency virus patient.
PMID- 28488651
TI - Successful management of a penetrating iron-rod injury through the oral cavity
involving the posterior cranial fossa.
PMID- 28488652
TI - Microcephaly with generalized dystonia: Exception to the rule.
PMID- 28488653
TI - Dengue encephalitis: "Double doughnut" sign.
PMID- 28488654
TI - Transcranial Doppler flow patterns in brain death: "Storm before the calm".
PMID- 28488655
TI - Carbon monoxide toxicity: A reversible damage to brain.
PMID- 28488656
TI - Humming bird sign, a significant sign.
PMID- 28488657
TI - Central pontine myelinolysis associated with hypokalemia in a diabetic patient
with sepsis.
PMID- 28488658
TI - Walker-Warburg syndrome with gonadal dysgenesis: A rare association.
PMID- 28488659
TI - Bilateral mirror image sphenoid wing meningiomas.
PMID- 28488660
TI - Duplicated origin of vertebral artery.
PMID- 28488661
TI - Dolichoectatic internal carotid artery presenting as a sellar-suprasellar mass
with symptomatic hydrocephalus.
PMID- 28488662
TI - Cerebral revascularization: The standard method of anastomosis or the newly
recommended technique?
PMID- 28488663
TI - Over-diagnosis of paroxysmal sympathetic hyperactivity.
PMID- 28488664
TI - Author's Reply: Cerebral revascularization: Fundamental difference between the
new and conventional technique.
PMID- 28488665
TI - Clinicopathological conferences: The fading art of playing Sherlock Holmes.
PMID- 28488666
TI - Stroke in children due to oral injury by a thread tied to a kite.
PMID- 28488667
TI - Authors' Reply: Clinicopathological conferences: The fading art of playing
Sherlock Holmes.
PMID- 28488668
TI - Authors' Reply: Stroke in children due to an oral injury.
PMID- 28488669
TI - Full-field perimetry in pituitary tumors.
PMID- 28488670
TI - Authors' Reply: Comprehensive neuro-ophthalmological assessment in pituitary
tumors.
PMID- 28488671
TI - Actively addressed single pixel full-colour plasmonic display.
AB - Dynamic, colour-changing surfaces have many applications including displays,
wearables and active camouflage. Plasmonic nanostructures can fill this role by
having the advantages of ultra-small pixels, high reflectivity and post
fabrication tuning through control of the surrounding media. However, previous
reports of post-fabrication tuning have yet to cover a full red-green-blue (RGB)
colour basis set with a single nanostructure of singular dimensions. Here, we
report a method which greatly advances this tuning and demonstrates a liquid
crystal-plasmonic system that covers the full RGB colour basis set, only as a
function of voltage. This is accomplished through a surface morphology-induced,
polarization-dependent plasmonic resonance and a combination of bulk and surface
liquid crystal effects that manifest at different voltages. We further
demonstrate the system's compatibility with existing LCD technology by
integrating it with a commercially available thin-film-transistor array. The
imprinted surface interfaces readily with computers to display images as well as
video.
PMID- 28488672
TI - Large polarization gradients and temperature-stable responses in compositionally
graded ferroelectrics.
AB - A range of modern applications require large and tunable dielectric,
piezoelectric or pyroelectric response of ferroelectrics. Such effects are
intimately connected to the nature of polarization and how it responds to
externally applied stimuli. Ferroelectric susceptibilities are, in general,
strongly temperature dependent, diminishing rapidly as one transitions away from
the ferroelectric phase transition (TC). In turn, researchers seek new routes to
manipulate polarization to simultaneously enhance susceptibilities and broaden
operational temperature ranges. Here, we demonstrate such a capability by
creating composition and strain gradients in Ba1-xSrxTiO3 films which result in
spatial polarization gradients as large as 35 MUC cm-2 across a 150 nm thick
film. These polarization gradients allow for large dielectric permittivity with
low loss (Er~775, tan delta<0.05), negligible temperature-dependence (13%
deviation over 500 degrees C) and high-dielectric tunability (greater than 70%
across a 300 degrees C range). The role of space charges in stabilizing
polarization gradients is also discussed.
PMID- 28488673
TI - Climate warming reduces the temporal stability of plant community biomass
production.
AB - Anthropogenic climate change has emerged as a critical environmental problem,
prompting frequent investigations into its consequences for various ecological
systems. Few studies, however, have explored the effect of climate change on
ecological stability and the underlying mechanisms. We conduct a field experiment
to assess the influence of warming and altered precipitation on the temporal
stability of plant community biomass in an alpine grassland located on the
Tibetan Plateau. We find that whereas precipitation alteration does not influence
biomass temporal stability, warming lowers stability through reducing the degree
of species asynchrony. Importantly, biomass temporal stability is not influenced
by plant species diversity, but is largely determined by the temporal stability
of dominant species and asynchronous population dynamics among the coexisting
species. Our findings suggest that ongoing and future climate change may alter
stability properties of ecological communities, potentially hindering their
ability to provide ecosystem services for humanity.
PMID- 28488674
TI - Corrigendum: Identification of RAN1 orthologue associated with sex determination
through whole genome sequencing analysis in fig (Ficus carica L.).
PMID- 28488676
TI - Introduction to the first ESHG/EJHG Anniversary issue.
PMID- 28488675
TI - Comparison of the efficiency of colorectal cancer screening programs based on age
and genetic risk for reduction of colorectal cancer mortality.
AB - Given that colorectal cancer risk depends partly on inherited factors, screening
program efficiency may be increased by incorporating genetic factors. We compared
the efficiency of screening based on age and genetic risk in a simulated
population. We simulated a population matching the size, age distribution and
colorectal cancer incidence and mortality of Australia. We also simulated the
distribution of genetic risk for colorectal cancer based on the expected number
of inherited risk alleles of 45 single-nucleotide polymorphisms (SNPs) previously
reported as associated with colorectal cancer. We compared the expected
colorectal cancer deaths under three screening programs; age-based, genetic-based
and combined age-based and genetic-based. The age-based program would prevent
25.4 deaths per 100 000 invited to screen, none of which would be under age 50;
the genetic program would prevent 26.2 deaths per 100 000 invited to screen, 16
of which would be under age 50; and the combined program would prevent 24.4
deaths per 100 000 invited to screen, 16 of which would be under age 50. Genetic
testing of 1.5 million 45-49 year olds would identify 91% of the people aged
under 50 at sufficient risk to warrant screening, potentially saving 16
colorectal cancer deaths each year. Screening eligibility based on genetic risk
profile for age is as efficient as eligibility based on age alone for preventing
colorectal cancer mortality, but identifies an additional 7% of the population at
sufficient risk to benefit from screening who would not normally be screened
given they are aged under 50 years.
PMID- 28488677
TI - Uninformed consent in nutrigenomic research.
AB - Genetic testing for personalizing diet and wellness programs is performed without
extensive counseling that informs about the potential implications of knowing
one's genotype status. Genetic counseling seems redundant for genes that impact
the effect of diet on biomarkers such as cholesterol and blood pressure, but the
same genes may have pleiotropic effects that cannot be ignored. A well-known
example is the APOE gene, which is implicated in cholesterol regulation and is a
major risk factor for Alzheimer's disease. Not fully informing participants about
the major pleiotropic effects of genes has ethical implications and invalidates
informed consent.
PMID- 28488678
TI - A missense variant in ITPR1 provides evidence for autosomal recessive SCA29 with
asymptomatic cerebellar hypoplasia in carriers.
AB - Spinocerebellar ataxias (SCA) comprise a heterogeneous group of inherited
neurological disorders characterized by a range of symptoms from both cerebellar
and extra cerebellar structures. We investigated the cause of autosomal
recessive, congenital SCA in six affected family members from a large
consanguineous family. Using whole-exome sequencing, we identified a homozygous
ITPR1 missense variant [c.5360T>C; p.(L1787P)] segregating in all affected
individuals. Heterozygous carriers were asymptomatic despite cerebellar
hypoplasia. Variants in the ITPTR1 gene have previously been associated
exclusively with autosomal dominant SCA15 and SCA29 with slow or no progression.
The L1787 residue is highly conserved and the leucine to proline substitution has
a predicted destabilizing effect on the protein structure. Additionally, the
L1787P variant is located in a domain separated from previously described and
dominant-acting missense variants consistent with a distinct effect on IP3R1
tetramer structure and function. Taken together, we show for the first time that
a biallelic ITPR1 missense variant may cause an autosomal recessive and infantile
onset SCA29, albeit with subclinical cerebellar hypoplasia in carriers. Our
findings add to the genetic complexity of SCA29 and broaden the correlations
between ITPR1 variants and their clinical expression.
PMID- 28488679
TI - The European Society of Human Genetics: beginnings, early history and development
over its first 25 years.
AB - The European Society of Human Genetics (ESHG) was founded on 15 March 1967, after
preliminary discussions at the International Human Genetics Congress in Chicago
the previous year and in Copenhagen in early 1967. Its initial meeting was held
on 18-19 November 1967, also in Copenhagen, and annual meetings have been held
from that time until the present, apart from years in which the International
Congress of Human Genetics was also being held. The character of the Society
during its early years was strongly influenced by its founding and permanent
Secretary, Jan Mohr, head of the Copenhagen Institute of Medical Genetics, whose
records are archived in the Tage Kemp/Jan Mohr Archive, now part of the Danish
National Archives. These records show Jan Mohr's determination to keep the
activities of the Society limited to the holding of an annual meeting to enhance
contacts between European human geneticists, and to resist expansion to other
activities. Pressures for a wider role of ESHG became irresistible in the late
1980s and a revised constitution, adopted in 1991, reshaped the Society into a
more conventional and less restrictive structure. This has allowed it to play a
wider and increasingly influential role in the development of human and medical
genetics across Europe, with its own Journal, a range of committees covering
different aspects of the field and a series of valuable reports on specific
important topics, to be described in a forthcoming article on the Society's more
recent history.European Journal of Human Genetics advance online publication, 10
May 2017; doi:10.1038/ejhg.2017.34.
PMID- 28488680
TI - Some pioneers of European human genetics.
AB - Some of the pioneers of human genetics across Europe are described, based on a
series of 100 recorded interviews made by the author. These interviews, and the
memories of earlier workers in the field recalled by interviewees, provide a
vivid picture, albeit incomplete, of the early years of human and medical
genetics. From small beginnings in the immediate post-World War 2 years, human
genetics grew rapidly across many European countries, a powerful factor being the
development of human cytogenetics, stimulated by concerns over the risks of
radiation exposure. Medical applications soon followed, with the recognition of
human chromosome abnormalities, the need for genetic counselling, the possibility
of prenatal diagnosis and later, the applications of human molecular genetics.
The evolution of the field has been strongly influenced by the characters and
interests of the relatively small number of founding workers in different
European countries, as well as by wider social, medical and scientific factors in
the individual countries.European Journal of Human Genetics advance online
publication, 10 May 2017; doi:10.1038/ejhg.2017.47.
PMID- 28488681
TI - Practices and views of neurologists regarding the use of whole-genome sequencing
in clinical settings: a web-based survey.
AB - The use of Whole-Genome Sequencing (WGS) in clinical settings has brought up a
number of controversial scientific and ethical issues. The application of WGS is
of particular relevance in neurology, as many conditions are difficult to
diagnose. We conducted a worldwide, web-based survey to explore neurologists'
views on the benefits of, and concerns regarding, the clinical use of WGS, as
well as the resources necessary to implement it. Almost half of the 204
neurologists in the study treated mostly adult patients (48%), while the rest
mainly children (37.3%), or both (14.7%). Epilepsy (73%) and headaches (57.8%)
were the predominant conditions treated. Factor analysis brought out two
profiles: neurologists who would offer WGS to their patients, and those who would
not, or were not sure in which circumstances it should be offered. Neurologists
considering the use of WGS as bringing more benefits than drawbacks currently
used targeted genetic testing (P<0.05) or treated mainly children (P<0.05). WGS'
benefits were directed towards the patients, while its risks were of a financial
and legal nature. Furthermore, there was a correlation between respondents'
current use of genetic tests and an anticipation of increased use in the future
(P<0.001). However, over half of respondents did not feel sufficiently informed
to use WGS in their practice (53.5%). Our results highlight gaps in education,
organization, and funding to support the use of WGS in neurology, and draw
attention to the need for resources that could strongly contribute to more
straightforward diagnoses and possibly better treatment of neurological
conditions.
PMID- 28488682
TI - Exome sequencing revealed a splice site variant in the IQCE gene underlying post
axial polydactyly type A restricted to lower limb.
AB - Polydactyly is characterized by an extra supernumerary digit/toe with or without
bony element. To date variants in four genes GLI3, ZNF141, MIPOL1 and PITX1 have
been implicated in developing non-syndromic form of polydactyly. The present
study involved characterization of large consanguineous family of Pakistani
origin segregating post-axial polydactyly type A, restricted to lower limb, in
autosomal recessive pattern. DNA of two affected members in the family was
subjected to exome sequencing. Sanger sequencing was then followed to validate
segregation of the variants in the family members. A homozygous splice acceptor
site variant (c.395-1G>A) was identified in the IQCE gene, which completely co
segregated with post-axial polydactyly phenotype within the family. The
homozygous variant was absent in different public variant databases, 7000 in
house exomes, 130 exomes from unrelated Pakistani individuals and 215 ethnically
matched controls. Mini-gene splicing assay was used to test effect of the variant
on function of the gene. The assay revealed loss of first nucleotide of exon 6,
producing a -1 frameshift and a premature stop codon 22 bases downstream of the
variant (p.Gly132Valfs*22). The study provided the first evidence of involvement
of the IQCE gene in limbs development in humans.
PMID- 28488683
TI - Progressive hereditary spastic paraplegia caused by a homozygous KY mutation.
AB - Twelve individuals of consanguineous Bedouin kindred presented with autosomal
recessive progressive spastic paraplegia evident as of age 0-24 months, with
spasticity of lower limbs, hyperreflexia, toe walking and equinus deformity.
Kyphoscolisois was evident in older patients. Most had atrophy of the lateral
aspects of the tongue and few had intellectual disability. Nerve conduction
velocity, electromyography and head and spinal cord magnetic resonance imaging
were normal in tested subjects. Muscle biopsy showed occasional central nuclei
and fiber size variability with small angular fibers. Genome-wide linkage
analysis identified a 6.7Mbp disease-associated locus on chromosome 3q21.3-3q22.2
(LOD score 9.02; D3S1290). Whole-exome sequencing identified a single homozygous
variant within this locus, c.51_52ins(28); p.(V18fs56*) in KY, segregating in the
family as expected and not found in 190 Bedouin controls. High KY transcript
levels were demonstrated in muscular organs with lower expression in the CNS. The
phenotype is reminiscent of kyphoscoliosis seen in Ky null mice. Two recent
studies done independently and parallel to ours describe somewhat similar
phenotypes in one and two patients with KY mutations. KY encodes a
tranglutaminase-like peptidase, which interacts with muscle cytoskeletal proteins
and is part of a Z-band protein complex, suggesting the disease mechanism may
resemble myofibrillar myopathy. However, the mixed myopathic-neurologic features
caused by human and mouse Ky mutations are difficult to explain by loss of KY
sarcomere stabilizing function alone. KY transcription in CNS tissues may imply
that it also has a role in neuromotor function, in line with the irregularity of
neuromuscular junction in Ky null mutant mice.
PMID- 28488684
TI - The impact of cholecalciferol supplementation on the systemic inflammatory
profile: a systematic review and meta-analysis of high-quality randomized
controlled trials.
AB - Causal links between vitamin D status [25(OH)D] and systemic inflammation were
examined through a systematic review of randomized controlled trials (RCTs).
Selected RCTs were ?12 weeks, conducted in adults free of acute inflammatory
disease, and of high-quality (Jadad score ?3). Of 14 studies that met our
criteria, 9 studies (15 study arms) permitted extraction of data. There was no
effect on the weighted mean difference (WMD) of IL-6 (WMD (95% confidence
interval)=0.1, (-0.166, 0.366) pg/ml, P=0.462) or C-reactive protein (CRP) (WMD=
0.324, (-1.007, 0.359) mg/l, P=0.352). Subgroup analyses of trials achieving ?80
nmol/l indicated a trend for lower CRP (WMD=-0.834, (-1.726, 0.058) mg/l,
P=0.067), however heterogeneity was significant (I2=66.7%, P=0.017). Studies
employing a low dose (<1000 IU/d) showed increased CRP (WMD=0.615, (0.132,
1.098), P=0.013). In contrast, ?1000 IU/d had a favourable effect on CRP (WMD=
0.939, (-1.805, -0.073), P=0.034) but heterogeneity was significant (I2=61.3%,
P=0.017). Meta-regression indicated that older age predicted a significant
decrease in IL-6 (beta=-0.02, (-0.034, -0.006) pg/ml, P=0.013) and CRP (beta=
0.06, (-0.103, -0.017), P=0.01), whereas a greater percentage of females
(beta=0.027, (0.011, 0.044), P=0.004) and longer study duration independently
predicted a higher WMD for CRP (beta=0.049, (0.018, 0.079), P=0.005). Available
high-quality RCTs did not support a beneficial effect of cholecalciferol on
systemic IL-6 and CRP. Future studies should consider the confounding effects of
age, gender and study duration, while possibly targeting an achieved 25(OH)D ?80
nmol/l.
PMID- 28488685
TI - Effect of diets rich in either saturated fat or n-6 polyunsaturated fatty acids
and supplemented with long-chain n-3 polyunsaturated fatty acids on plasma
lipoprotein profiles.
AB - BACKGROUND/OBJECTIVES: Abnormalities in lipoprotein profiles (size, distribution
and concentration) play an important role in the pathobiology of atherosclerosis
and coronary artery disease. Dietary fat, among other factors, has been
demonstrated to modulate lipoprotein profiles. We aimed to investigate if
background dietary fat (saturated, SFA versus omega-6 polyunsaturated fatty
acids, n-6PUFA) was a determinant of the effects of LCn-3PUFA supplementation on
lipoprotein profiles. SUBJECTS/METHODS: A randomized controlled clinical
intervention trial in a parallel design was conducted. Healthy subjects (n=26)
were supplemented with 400 mg eicosapentaenoic acid plus 2000 mg docosahexaenoic
acid daily and randomized to consume diets rich in either SFA or n-6PUFA for a
period of 6 weeks. Blood samples, collected at baseline and after 6 weeks of
intervention, were assessed for plasma lipoprotein profiles (lipoprotein size,
concentration and distribution in subclasses) determined using nuclear magnetic
resonance spectroscopy. RESULTS: Study participants receiving the SFA or the n
6PUFA enriched diets consumed similar percentage energy from fat (41 and 42%
respectively, P=0.681). However, subjects on the SFA diet consumed 50% more
energy as saturated fat and 77% less as linoleic acid than those consuming the n
6PUFA diet (P<0.001). The diets rich in SFA and n-6PUFA reduced the concentration
of total very-low-density lipoprotein (VLDL) particles (P<0.001, both), and their
subclasses and increased VLDL (P=0.042 and P=0.007, respectively) and LDL
(P=0.030 and 0.027, respectively) particle size. In addition, plasma triglyceride
concentration was significantly reduced by LCn-3PUFA supplementation irrespective
of the dietary fat. CONCLUSIONS: LCn-3PUFA modulated lipoprotein profiles in a
similar fashion when supplemented in diets rich in either SFA or n-6PUFA.
PMID- 28488686
TI - An overview of folate status in a population-based study from Sao Paulo, Brazil
and the potential impact of 10 years of national folic acid fortification policy.
AB - BACKGROUND/OBJECTIVES: Food fortification is an important strategy in public
health policy for controlling micronutrient malnutrition and a major contributing
factor in the eradication of micronutrients' deficiencies. Approximately 50
countries worldwide have adopted food fortification with folic acid (FA). FA
fortification of wheat and maize flours has been mandatory in Brazil since 2004.
To assess the effect of 10 years of FA food fortification policy on folate status
of residents of Sao Palo, Brazil using a population-based survey.
SUBJECTS/METHODS: Data were from 750 individuals aged ?12 years who participated
in a cross-sectional population-based survey in Sao Paulo city, Brazil. Fasting
blood samples were collected, and folate was assayed by affinity-high performance
liquid chromatografy method with electrochemical detection. The participants
provided information about food intake based on two 24 h dietary recall. RESULTS:
Only 1.76% of population had folate deficiency (<6.8 nmol/l). The mean folate
concentration was 29.5 (95% confidence interval: 27.3-31.7) nmol/l for all sex
age groups. The mean folate intake for the population was 375.8 (s.e.m.=6.4)
MUg/day of dietary folate equivalents (DFEs). When comparing folate intake in DFE
from food folate and FA from fortified foods, FA contributed 50% or more of the
DFE in almost all sex-age groups. The major contributors of folate intake are
processed foods made from wheat flour fortified with FA, especially among
subjects younger than 20 years old. CONCLUSIONS: The deficiency of folate is very
low, and food fortification contributed to folate intake and had a notable
influence on rankings of food contributors of folate.
PMID- 28488687
TI - Does diet intervention in line with nutrition recommendations affect dietary
carbon footprint? Results from a weight loss trial among lactating women.
AB - BACKGROUND/OBJECTIVES: Results from studies evaluating the sustainability of
diets combining environmental and nutritional aspects have been diverse; thus,
greenhouse gas emissions (that is, carbon footprint (CF)) of diets in line with
dietary recommendations in free-living individuals warrants further examination.
Here, changes in dietary CF related to changes in food choice during a weight
loss trial among lactating women who received a 12-week diet intervention based
on the Nordic Nutrition Recommendations (NNR) 2004 were analyzed. The objective
of this study was to examine if a diet intervention based on NNR 2004 results in
reduced dietary CF. SUBJECTS/METHODS: Changes in dietary CF were analyzed among
61 lactating women participating in a weight loss trial. Food intake data from 4
day weighed diet records and results from life cycle analyses were used to
examine changes in dietary CF across eight food groups during the intervention,
specified in the unit carbon dioxide equivalent (CO2eq/day). Differences in
changes in dietary CF between women receiving diet treatment (D-group) and women
not receiving it (ND-group) were compared. RESULTS: There was no difference in
change in dietary CF of the overall diet between D- and ND-group (P>0.05). As for
the eight food groups, D-group increased their dietary CF from fruit and
vegetables (+0.06+/-0.13 kg CO2eq/day) compared with a decrease in ND-group (
0.01+/-0.01 kg CO2eq/day) during the intervention, P=0.01. CONCLUSIONS: A diet
intervention in line with NNR 2004 produced clinically relevant weight loss, but
did not reduce dietary CF among lactating women with overweight and obesity.
Dietary interventions especially designed to decrease dietary CF and their
coherence with dietary recommendations need further exploration.
PMID- 28488688
TI - Association between coffee or tea drinking and Barrett's esophagus or
esophagitis: an Italian study.
AB - BACKGROUND/OBJECTIVES: Only a few papers have treated of the relationship between
Barrett's esophagus (BE) or erosive esophagitis (E) and coffee or tea intake. We
evaluated the role of these beverages in BE and E occurrence. SUBJECTS/METHODS:
Patients with BE (339), E (462) and controls (619) were recruited. Data on coffee
and tea and other individual characteristics were collected using a structured
questionnaire. RESULTS: BE risk was higher in former coffee drinkers,
irrespective of levels of exposure (cup per day; ?1: OR=3.76, 95% CI 1.33-10.6;
>1: OR=3.79, 95% CI 1.31-11.0; test for linear trend (TLT) P=0.006) and was
higher with duration (>30 years: OR=4.18, 95% CI 1.43-12.3; TLT P=0.004) and for
late quitters, respectively (?3 years from cessation: OR=5.95, 95% CI 2.19-16.2;
TLT P<0.001). The risk of BE was also higher in subjects who started drinking
coffee later (age >18 years: OR=6.10, 95% CI 2.15-17.3). No association was found
in current drinkers, but for an increased risk of E in light drinkers (<1 cup per
day OR =1.85, 95% CI 1.00-3.43).A discernible risk reduction of E (about 20%, not
significant) and BE (about 30%, P<0.05) was observed in tea drinkers.
CONCLUSIONS: Our data were suggestive of a reduced risk of BE and E with tea
intake. An adverse effect of coffee was found among BE patients who had stopped
drinking coffee. Coffee or tea intakes could be indicative of other lifestyle
habits with protective or adverse impact on esophageal mucosa.
PMID- 28488689
TI - Effects of vitamin D or its analogues on the mortality of patients with chronic
kidney disease: an updated systematic review and meta-analysis.
AB - The objective of this study was to assess whether vitamin D (VD) treatment alters
the overall all-cause and cardiovascular mortalities in a chronic kidney disease
(CKD) population. We systematically searched PubMed, EMBASE, Web of Science, and
Cochrane Central Register of Controlled Trials without language restriction,
until the publication date of 22 February 2016. All related literatures that
compared VD treatment with non-VD treatment and reported the mortality of
patients with CKD (including those undergoing dialysis) were identified. Pooled
risk ratios (RR) and 95% confidence intervals (CI) were calculated by using the
random- and fixed-effects models. Randomised controlled trials (RCTs) that used
the intention-to-treat principle and observational studies (OSs) were analysed
separately. For this study, 38 studies involving 223 429 patients (17 RCTs,
n=1819 and 21 OSs, n=221610) were included. In the OSs, VD treatment was
significantly associated with reductions in both all-cause and cardiovascular
mortalities; however, such significant association was not found in the RCTs. The
existing RCTs do not provide sufficient or precise evidence that VD
supplementation affects the mortality of patients with CKD, although subsets of
patients that could potentially benefit from VD treatment can be identified by
using the existing data from the RCTs. Nevertheless, large-size RCTs are needed
in the future to assess any potential differences in survival prospectively.
PMID- 28488690
TI - Soyfood and isoflavone intake and risk of type 2 diabetes in Vietnamese adults.
AB - BACKGROUND/OBJECTIVES: Animal studies have demonstrated that soy isoflavones
exert antidiabetic effects. However, evidence regarding the association between
soyfood intake, a unique source of isoflavones, and type 2 diabetes remains
inconclusive. This study assessed the relationship between habitual intakes of
soyfoods and major isoflavones and risk of type 2 diabetes in Vietnamese adults.
SUBJECTS/METHODS: A hospital-based case-control study was conducted in Vietnam
during 2013-2015. A total of 599 newly diagnosed diabetic cases (age 40-65 years)
and 599 hospital-based controls, frequency matched by age and sex, were recruited
in Hanoi, capital city of Vietnam. Information on frequency and quantity of
soyfood and isoflavone intake, together with demographics, habitual diet and
lifestyle characteristics, was obtained from direct interviews using a validated
and reliable questionnaire. Unconditional logistic regression analyses were
performed to examine the association between soy variables and type 2 diabetes
risk. RESULTS: Higher intake of total soyfoods was significantly associated with
a lower risk of type 2 diabetes; the adjusted odds ratio (OR) for the highest
versus the lowest intake was 0.31 (95% confidence interval (CI): 0.21-0.46;
P<0.001). An inverse dose-response relationship of similar magnitude was also
observed for total isoflavone intake (OR: 0.35; 95% CI: 0.24 to 0.49; P<0.001).
In addition, inverse associations of specific soyfoods (soy milk, tofu and mung
bean sprout) and major isoflavones (daidzein, genistein and glycitein) with the
type 2 diabetes risk were evident. CONCLUSIONS: Soyfood and isoflavone intake was
associated with a lower type 2 diabetes risk in Vietnamese adults.
PMID- 28488691
TI - Interaction effect of PGC-1alpha rs10517030 variants and energy intake in the
risk of type 2 diabetes in middle-aged adults.
AB - BACKGROUND/OBJECTIVES: PGC-1alpha is an important regulatory factor for energy
and glucose metabolism. Therefore, we investigated whether the PGC-1alpha
genotype (rs10517030 and rs10212638) affects the incidence of type 2 diabetes
mellitus (T2DM) and sought to explain the interactions between their variants and
nutrient intake on the development of T2DM. SUBJECTS/METHODS: Subjects aged 40-65
years of both genders were from the Ansung/Ansan cohorts (8842 adults) in Korea.
Associations of PGC-1alpha variants rs10517030 and rs10212638 with T2DM were
analyzed in a dominant genetic model, and were tested for interactions of
genotypes and nutrients with T2DM risk. It was adjusted for covariates related to
glucose metabolism. RESULTS: Three variants, rs10517030, rs10517032 and
rs10212638, were positively associated with T2DM prevalence. Single-nucleotide
polymorphisms, rs10517030 and rs10517032, had strong association (r2=0.963). In
the glucose tolerance tests, odds ratios (ORs) for serum glucose levels at 120
min were higher for subjects who were in the minor-allele group (minor allele
homozygotes and heterozygotes) than for the major-allele group (major allele
homozygotes) for rs10517030 variants. Serum insulin levels at 60 min had a lower
ORs in the minor-allele group of rs10517030 variants. The interaction between
energy intake and PGC-1alpha rs10517030 variants also affected T2DM risk. PGC
1alpha minor alleles were linked to T2DM prevalence and homeostasis model
assessment estimate of insulin resistance (HOMA-IR) only in the low-energy
groups, and HOMA-B was significantly negatively associated with the minor-allele
group of PGC-1alpha rs10517030 variants, only in the low-energy-intake groups.
CONCLUSIONS: These data suggest that Koreans with the minor alleles of PGC-1alpha
rs10517030, rs10517032 and rs10212638 are at greater risk of T2DM, and that a low
energy diet is more protective against the development of T2DM in subjects with
the major alleles of rs10517030 and rs10517032.
PMID- 28488692
TI - Mediterranean diet and multiple health outcomes: an umbrella review of meta
analyses of observational studies and randomised trials.
AB - Research has shown that a greater adherence to the Mediterranean diet is
associated with a reduced risk of major chronic disease. However, the existing
literature leads to debate for different issues, such as the measurement of the
adherence to the Mediterranean diet, the use of a wide variety of dietary indices
with various food components and the large heterogeneity across the studies. In
order to summarise the evidence and evaluate the validity of the association
between the adherence to the Mediterranean diet and multiple health outcomes, an
umbrella review of the evidence across meta-analyses of observational studies and
randomised clinical trials (RCTs) was performed. Thirteen meta-analyses of
observational studies and 16 meta-analyses of RCTs investigating the association
between the adherence to the Mediterranean diet and 37 different health outcomes,
for a total population of over than 12 800 000 subjects, were identified. A
robust evidence, supported by a P-value<0.001, a large simple size, and not a
considerable heterogeneity between studies, for a greater adherence to the
Mediterranean diet and a reduced the risk of overall mortality, cardiovascular
diseases, coronary heart disease, myocardial infarction, overall cancer
incidence, neurodegenerative diseases and diabetes was found. For most of the
site-specific cancers, as well as for inflammatory and metabolic parameters, the
evidence was only suggestive or weak and further studies are needed to draw
firmer conclusions. No evidence, on the other hand, was reported for bladder,
endometrial and ovarian cancers, as well as for LDL (low density lipoprotein)
cholesterol levels.
PMID- 28488693
TI - ICOS protects against mortality from acute lung injury through activation of IL
5+ ILC2s.
AB - Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease causing
irreversible lung scarring and loss of pulmonary function. IPF Patients suffer
from a high rate of pulmonary infections and acute exacerbations of disease that
further contribute to pulmonary decline. Low expression of the inducible T-cell
costimulatory molecule (ICOS) in peripheral blood mononuclear cells predicts
decreased survival of IPF patients, but the mechanisms by which ICOS protects are
unclear. Using a model of bleomycin-induced lung injury and fibrosis, we now
demonstrate that ICOS expression enhances survival from lung injury rather than
regulating fibrogenesis. Of ICOS-expressing cells, type 2 innate lymphocytes
(ILC2s) are the first to respond to bleomycin-induced injury, and this expansion
is ICOS dependent. Interestingly, a similar decrease in ICOS+ ILCs was found in
lung tissue from IPF patients. Interleukin (IL)-5, produced primarily by ILC2s,
was significantly reduced after lung injury in ICOS-/- mice, and strikingly,
treatment with IL-5 protected both ICOS-/- and wild-type mice from mortality.
These results imply that low ICOS expression and decreased lung ILC2s in IPF
patients may contribute to poor recovery from infections and acute exacerbation
and that IL-5 treatment may be a novel therapeutic strategy to overcome these
defects and protect against lung injury.
PMID- 28488694
TI - Light-induced unfolding and refolding of supramolecular polymer nanofibres.
AB - Unlike classical covalent polymers, one-dimensionally (1D) elongated
supramolecular polymers (SPs) can be encoded with high degrees of internal order
by the cooperative aggregation of molecular subunits, which endows these SPs with
extraordinary properties and functions. However, this internal order has not yet
been exploited to generate and dynamically control well-defined higher-order
(secondary) conformations of the SP backbone, which may induce functionality that
is comparable to protein folding/unfolding. Herein, we report light-induced
conformational changes of SPs based on the 1D exotic stacking of hydrogen-bonded
azobenzene hexamers. The stacking causes a unique internal order that leads to
spontaneous curvature, which allows accessing conformations that range from
randomly folded to helically folded coils. The reversible photoisomerization of
the azobenzene moiety destroys or recovers the curvature of the main chain, which
demonstrates external control over the SP conformation that may ultimately lead
to biological functions.
PMID- 28488695
TI - Blockade of IDO-kynurenine-AhR metabolic circuitry abrogates IFN-gamma-induced
immunologic dormancy of tumor-repopulating cells.
AB - Interactions with the immune system may lead tumorigenic cells into dormancy.
However, the underlying molecular mechanism is poorly understood. Using a 3D
fibrin gel model, we show that IFN-gamma induces tumour-repopulating cells (TRCs)
to enter dormancy through an indolamine 2,3-dioxygenase 1 (IDO1)-kynurenine (Kyn)
aryl hydrocarbon receptor (AhR)-p27 dependent pathway. Mechanistically, IFN-gamma
signalling triggers differentiated tumour cell apoptosis via STAT1; however, when
IDO1 and AhR are highly expressed as in TRCs, IFN-gamma results in IDO1/AhR
dependent p27 induction that prevents STAT1 signalling, thus suppressing the
process of cell death and activating the dormancy program. Blocking the IDO/AhR
metabolic circuitry not only abrogates IFN-gamma-induced dormancy but also
results in enhanced repression of tumour growth by IFN-gamma-induced apoptosis of
TRCs both in vitro and in vivo. These data present a previously unrecognized
mechanism of inducing TRC dormancy by IFN-gamma, suggesting a potential effective
cancer immunotherapeutic modality through the combination of IFN-gamma and
IDO/AhR inhibitors.
PMID- 28488696
TI - Functional roles of cadherin, aminopeptidase-N and alkaline phosphatase from
Helicoverpa armigera (Hubner) in the action mechanism of Bacillus thuringiensis
Cry2Aa.
AB - A pyramid strategy combining the Cry1A and Cry2A toxins in Bt crops has been
widely used throughout the world to delay pest adaption to transgenic crops and
broaden the insecticidal spectrum. Midgut membrane-bound cadherin (CAD),
aminopeptidase-N (APN) and alkaline phosphatase (ALP) are important for Cry1A
toxicity in some lepidopteran larvae, but the proteins that bind Cry2A in the
midgut of target insects and their role in the Cry2A mechanism of action are
still unclear. In this study, we found that heterologously expressed CAD, APN4
and ALP2 peptides from the midgut of Helicoverpa armigera could bind to the
Cry2Aa toxin with a high affinity. Additionally, the efficiency of Cry2Aa
insecticidal activity against H. armigera larvae was obviously reduced after the
genes encoding these proteins were silenced with specific siRNAs: CAD- and ALP2
silenced larvae showed significantly similar reductions in mortality due to the
Cry2Aa toxin (41.67% and 43.06%, respectively), whereas a larger reduction in
mortality was observed in APN4-silenced larvae (61.11%) than in controls. These
results suggest that CAD, APN4 and ALP2 are involved in the mechanism of action
of Cry2Aa in H. armigera and may play important functional roles in the toxicity
of the Cry2Aa toxin.
PMID- 28488697
TI - Selective C70 encapsulation by a robust octameric nanospheroid held together by
48 cooperative hydrogen bonds.
AB - Self-assembly of multiple building blocks via hydrogen bonds into well-defined
nanoconstructs with selective binding function remains one of the foremost
challenges in supramolecular chemistry. Here, we report the discovery of a
enantiopure nanocapsule that is formed through the self-assembly of eight amino
acid functionalised molecules in nonpolar solvents through 48 hydrogen bonds. The
nanocapsule is remarkably robust, being stable at low and high temperatures, and
in the presence of base, presumably due to the co-operative geometry of the
hydrogen bonding motif. Thanks to small pore sizes, large internal cavity and
sufficient dynamicity, the nanocapsule is able to recognize and encapsulate large
aromatic guests such as fullerenes C60 and C70. The structural and electronic
complementary between the host and C70 leads to its preferential and selective
binding from a mixture of C60 and C70.
PMID- 28488698
TI - The Rhizobium tropici CIAT 899 NodD2 protein regulates the production of Nod
factors under salt stress in a flavonoid-independent manner.
AB - In the symbiotic associations between rhizobia and legumes, NodD promotes the
expression of the nodulation genes in the presence of appropriate flavonoids.
This set of genes is implied in the synthesis of Nodulation factors, which are
responsible for launching the nodulation process. Rhizobium tropici CIAT 899 is
the most successful symbiont of Phaseolus vulgaris and can nodulate a variety of
legumes. This strain produces Nodulation factors under abiotic stress such as
acidity or high concentration of salt. Genome sequencing of CIAT 899 allowed the
identification of five nodD genes. Whereas NodD1 is essential to nodulate
Leucaena leucocephala, Lotus japonicus and Macroptilium atropurpureum, symbiosis
with P. vulgaris and Lotus burtii decreased the nodule number but did not abolish
the symbiotic process when NodD1 is absent. Nodulation factor synthesis under
salt stress is not regulated by NodD1. Here we confirmed that NodD2 is
responsible for the activation of the CIAT 899 symbiotic genes under salt stress.
We have demonstrated that NodD1 and NodD2 control the synthesis of the Nod factor
necessary for a successful symbiosis with P. vulgaris and L. burtii. This is the
first time that NodD is directly implied in the activation of the symbiotic genes
under an abiotic stress.
PMID- 28488699
TI - Charting the unknown epitranscriptome.
AB - RNA modifications can alter RNA structure-function relationships and various
cellular processes. However, the genomic distribution and biological roles of
most RNA modifications remain uncharacterized. Here, we propose using phage
display antibody technology and direct sequencing through nanopores to facilitate
systematic interrogation of the distribution, location and dynamics of RNA
modifications.
PMID- 28488701
TI - RNA decay: The anti-apoptotic function of ADAR1.
PMID- 28488700
TI - Alternative splicing as a regulator of development and tissue identity.
AB - Alternative splicing of eukaryotic transcripts is a mechanism that enables cells
to generate vast protein diversity from a limited number of genes. The mechanisms
and outcomes of alternative splicing of individual transcripts are relatively
well understood, and recent efforts have been directed towards studying splicing
networks. It has become apparent that coordinated splicing networks regulate
tissue and organ development, and that alternative splicing has important
physiological functions in different developmental processes in humans.
PMID- 28488702
TI - Mechanisms of diseases: Excessive polyQ tracts curb autophagy.
PMID- 28488704
TI - Targeting curcumin to specific tumour cell environments: the influence of
ancillary ligands.
AB - Tumour-activation of prodrugs has the potential to improve the efficacy of
anticancer agents while minimising systemic toxicity. Cobalt complexes are of
interest in this respect as chaperones to deliver and release anticancer agents
in the low oxygen, reducing environment of solid tumours. In addition to being
able to release a cytotoxic ligand under the conditions of the tumour
microenvironment, it is fundamental that the chaperone complex must also be able
to penetrate through multiple cell layers to deliver the cytotoxin to all regions
of the tumour. Herein, we report an investigation of the distribution and
metabolism of two chaperone complexes of the anticancer agent curcumin within
monolayer tumour cells and multicellular tumour spheroids. Using a combination of
X-ray fluorescence microscopy, confocal fluorescence microscopy, and X-ray
absorption spectroscopy, we demonstrate how the nature of the chaperone complex
can profoundly influence the cellular uptake, distribution, and release mechanism
of curcumin, providing key insights into the design of this class of prodrug.
PMID- 28488705
TI - Ni/Co/Ti layered double hydroxide for highly efficient photocatalytic degradation
of Rhodamine B and Acid Red G: a comparative study.
AB - Optically responsive, luminescent Ni/Co/Ti layered double hydroxide (LDH),
synthesized by a single step hydrothermal route, exhibits highly efficient
photodegradation of cationic and anionic dyes, Rhodamine B (~99.8%) and Acid Red
G (~99.6%) respectively, better than that of commercial catalysts like NiO, CoO
and TiO2. The LDH has been characterized by using XRD, XPS, PL, TRES, EIS, TEM,
SEM-EDX, AFM, UV-visible DRS, N2-sorption desorption, xi-potential, FT-IR and TG
techniques. The characterized results indicate that the LDH possesses hexagonal
morphology, a high surface area, a narrow band gap, defect states and oxygen
vacancies within its layered framework. The degradations follow the e--h+ hopping
pattern and dye-photosensitized mechanistic pathways. The active species
generated during photocatalysis have been evaluated using ESR, terephthalic acid
fluorescence probe and indirect radical-hole trapping experiments. The colourless
end products were investigated by GC-MS and reaction mechanisms have been
established for the degradation of the dyes to less toxic and more eco-friendly
molecules than their parent analogues. Dye mineralization studies (performed
using a TOC analyser) and closure of carbon mass balance experiments quantified
the amount of carbon entering and leaving the reaction systems. Reaction
mechanisms have been proposed on the basis of the asymmetric cleavage of the
dyes. The LDH demonstrated its remarkable efficiency in the field of waste water
treatment.
PMID- 28488703
TI - Protein O-GlcNAcylation: emerging mechanisms and functions.
AB - O-GlcNAcylation - the attachment of O-linked N-acetylglucosamine (O-GlcNAc)
moieties to cytoplasmic, nuclear and mitochondrial proteins - is a post
translational modification that regulates fundamental cellular processes in
metazoans. A single pair of enzymes - O-GlcNAc transferase (OGT) and O-GlcNAcase
(OGA) - controls the dynamic cycling of this protein modification in a nutrient-
and stress-responsive manner. Recent years have seen remarkable advances in our
understanding of O-GlcNAcylation at levels that range from structural and
molecular biology to cell signalling and gene regulation to physiology and
disease. New mechanisms and functions of O-GlcNAcylation that are emerging from
these recent developments enable us to begin constructing a unified conceptual
framework through which the significance of this modification in cellular and
organismal physiology can be understood.
PMID- 28488706
TI - Impact of aryloxy initiators on the living and immortal polymerization of
lactide.
AB - This report describes two different methodologies for the synthesis of aryl end
functionalized poly(lactide)s (PLAs) catalyzed by indium complexes. In the first
method, a series of para-functionalized phenoxy-bridged dinuclear indium
complexes [(NNO)InCl]2(MU-Cl)(MU-OPhR) (R = OMe (1), Me (2), H (3), Br (4), NO2
(5)) were synthesized and fully characterized. The solution and solid state
structures of these complexes reflect the electronic differences between these
initiators. The polymerization rates correlate with the electron donating ability
of the phenoxy initiators: the para-nitro substituted complex 5 is essentially
inactive. However, the para-methoxy variant, while less active than the ethoxy
bridged complex [(NNO)InCl]2(MU-Cl)(MU-OEt) (A), shows sufficient activity.
Alternatively, aryl-capped PLAs were synthesized via immortal polymerization of
PLA with A in the presence of a range of arylated chain transfer agents. Certain
aromatic diols shut down polymerization by chelating one indium centre to form a
stable metal complex. Immortal ROP was successful when using phenol, and 1,5
naphthalenediol. These polymers were analysed and chain end fidelity was
confirmed using 1H NMR spectroscopy, MALDI-TOF mass spectrometry, and UV-Vis
spectroscopy. This study shed light on possible speciation when attempting to
generate PLA-lignin copolymers.
PMID- 28488707
TI - Emergent properties of extracellular vesicles: a holistic approach to decode the
complexity of intercellular communication networks.
AB - Shedding of nano-sized bilayered extracellular vesicles and extracellular vesicle
mediated intercellular communication are evolutionarily conserved biological
processes. Communication between cells and the environment is an essential
process in living organisms and dysregulation of intercellular communication
leads to various diseases. Thus, systematic studies on extracellular vesicles,
also known as exosomes, microvesicles, and outer membrane vesicles, are critical
for a deeper understanding of intercellular communication networks that are
crucial for decoding the exact causes of various difficult-to-cure diseases.
Recent progress in this emerging field reveals that extracellular vesicles are
endogenous carriers of specific subsets of proteins, mRNAs, miRNAs, and other
bioactive materials, as well as play diverse pathophysiological roles. However,
certain issues regarding diverse subtypes and the complex pathophysiological
roles of extracellular vesicles are not yet clearly elucidated. In this review,
we first briefly introduce the complexity of extracellular vesicles in terms of
their vesicular cargos and protein-protein interaction networks, their diverse
subtypes, and multifaceted pathophysiological functions. Then, we introduce the
limitation of reductionist approaches in understanding the complexity of
extracellular vesicles. We finally suggest that molecular systems biology
approaches based on the concept of emergent properties are essential for a
comprehensive understanding of the complex pathophysiological functions of
heterogeneous extracellular vesicles, either at the single vesicle level or at a
systems level as a whole.
PMID- 28488709
TI - Shear viscosity in hard-sphere and adhesive colloidal suspensions with reverse
non-equilibrium molecular dynamics.
AB - We employ the reverse non-equilibrium molecular dynamics method (RNEMD) of Muller
Plathe [Phys. Rev. E, 1999, 59, 4894] to calculate the shear viscosity of
colloidal suspensions within the stochastic rotation dynamics-molecular dynamics
(SRD-MD) simulation method. We examine the influence of different coupling
schemes in SRD-MD on the colloidal volume fraction phic dependent viscosity from
the dilute limit up to phic = 0.3. Our results demonstrate that the RNEMD method
is a robust and reliable method for calculating rheological properties of
colloidal suspensions. To obtain quantitatively accurate results beyond the
dilute regime, the hydrodynamic interactions between the effective fluid
particles in the SRD and the MD colloidal particles must be carefully considered
in the coupling scheme. We benchmark the method by comparing with the hard sphere
suspension case, and then calculate relative viscosities for colloids with
mutually attractive interactions. We show that the viscosity displays a sharp
increase at the onset of aggregation of the colloidal particles with increasing
volume fraction and attraction.
PMID- 28488710
TI - Electric field directed formation of aligned conjugated polymer fibers.
AB - Alternating current (AC) electric fields effectively align poly(3-alkylthiophene)
(P3AT) fibers during a one-dimensional crystallization process. Structural,
mechanical and electrical properties have been probed using microscopy, small
angle neutron scattering (SANS), atomic force microscopy (AFM), X-ray diffraction
(XRD), rheology, UV-Vis spectroscopy, and dielectric spectroscopy. Optimum
frequency and amplitudes were identified for specific P3AT concentrations and for
variable solvent quality. Optical microscopy along with SANS and XRD demonstrate
alignment persists over both micrometer and nanometer length scales. Small
amplitude oscillatory shear rheology also showed that the shear modulus increased
for aligned fibers. The structural changes were correlated to improvements in
electric conductivity as probed by dielectric spectroscopy. XRD experiments
performed with variable sample orientations also showed that the P3HT pi-pi
stacking direction was aligned parallel to the direction of the fiber axis.
Electric field alignment was also possible for other alkyl-thiophene polymers and
for polymers with simple backbone repeat units.
PMID- 28488712
TI - Probing the interactions of organic molecules, nanomaterials, and microbes with
solid surfaces using quartz crystal microbalances: methodology, advantages, and
limitations.
AB - Quartz crystal microbalances (QCMs) provide a new analytical opportunity and
prospect to characterize many environmental processes at solid/liquid interfaces,
thanks to their almost real-time measurement of physicochemical changes on their
quartz sensor. This work reviews the applications of QCMs in probing the
interactions of organic molecules, nanomaterials (NMs) and microbes with solid
surfaces. These interfacial interactions are relevant to critical environmental
processes such as biofilm formation, fate and transport of NMs, fouling in
engineering systems and antifouling practices. The high sensitivity, real-time
monitoring, and simultaneous frequency and dissipation measurements make QCM-D a
unique technique that helps reveal the interaction mechanisms for the
abovementioned processes (e.g., driving forces, affinity, kinetics, and the
interplay between surface chemistry and solution chemistry). On the other hand,
QCM measurement is nonselective and spatially-dependent. Thus, caution should be
taken during data analysis and interpretation, and it is necessary to cross
validate the results using complementary information from other techniques for
more quantitative and accurate interpretation. This review summarizes the general
methodologies for collecting and analyzing raw QCM data, as well as for
evaluating the associated uncertainties. It serves to help researchers gain
deeper insights into the fundamentals and applications of QCMs, and provides new
perspectives on future research directions.
PMID- 28488714
TI - A hierarchical NiO/NiMn-layered double hydroxide nanosheet array on Ni foam for
high performance supercapacitors.
AB - A hierarchical NiO/NiMn-LDH nanosheet array on Ni foam was prepared via a facile
two-step approach and exhibited a high specific capacitance (937 F g-1 at 0.5 A g
1) and good cycling stability (91% retention after 1000 cycles at 5 A g-1). The
improved electrochemical performance is benefited from the synergistic properties
of hierarchical NiO/LDH nanosheet composites on a conductive substrate.
PMID- 28488715
TI - van der Waals interaction between a moving nano-cylinder and a liquid thin film.
AB - We study the static and dynamic interaction between a horizontal cylindrical nano
probe and a thin liquid film. The effects of the physical and geometrical
parameters, with a special focus on the film thickness, the probe speed, and the
distance between the probe and the free surface are analyzed. Deformation
profiles have been computed numerically from a Reynolds lubrication equation,
coupled to a modified Young-Laplace equation, which takes into account the
probe/liquid and the liquid/substrate non-retarded van der Waals interactions. We
have found that the film thickness and the probe speed have a significant effect
on the threshold separation distance below which the jump-to-contact instability
is triggered. These results encourage the use of horizontal cylindrical nano
probes to scan thin liquid films, in order to determine either the physical or
geometrical properties of the latter, through the measurement of interaction
forces.
PMID- 28488717
TI - Endothelial monolayer permeability under controlled oxygen tension.
AB - Endothelial permeability has been extensively investigated in the context of
pathologies such as cancer and also in studies of drug delivery from the
circulation. Hypoxia is a critical regulator of endothelial cell (EC) behavior
and affects the barrier function of endothelial linings, yet its role has been
little studied. This paper reveals the effect of hypoxia on the permeability of
an EC monolayer by cellular experiments using a microfluidic device and a
conventional cell culture dish. Human umbilical vein endothelial cells (HUVECs)
were seeded into one microfluidic channel, creating an EC monolayer on each
vertical surface of a collagen gel confined to a central chamber. Oxygen tension
was regulated to produce normoxic (21% O2) or hypoxic (3% O2) conditions by the
supply of gas mixtures of oxygen, carbon dioxide, and nitrogen at predefined
ratios into channels fabricated into the device. Permeability of the EC monolayer
quantified by analyzing diffusion of fluorescence-labelled dextrans into the
collagen gel increases with barrier function loss by 6 hour hypoxic exposure,
showing 11-fold and 4-fold increases for 70 kDa and 10 kDa dextrans,
respectively, on average. Consistent with this, subsequent immunofluorescent
staining and separate western blot analysis of HUVECs on a culture dish
demonstrate loose cell-cell adhesion resulting from internalization of VE
cadherin under hypoxia. Thus, hypoxic stress increases endothelial permeability
by altering cell-cell junction integrity.
PMID- 28488718
TI - Nonspherical armoured bubble vibration.
AB - In this paper, we study the dynamics of cylindrical armoured bubbles excited by
mechanical vibrations. A step by step transition from cylindrical to spherical
shape is reported as the intensity of the vibration is increased, leading to a
reduction of the bubble surface and a dissemination of the excess particles. We
demonstrate through energy balance that nonspherical armoured bubbles constitute
a metastable state. The vibration instills the activation energy necessary for
the bubble to return to its least energetic stable state: a spherical armoured
bubble. At this point, particle desorption can only be achieved through higher
amplitude of excitation required to overcome capillary retention forces.
Nonspherical armoured bubbles open perspectives for tailored localized particle
dissemination with limited excitation power.
PMID- 28488719
TI - Non-edible parts of Solanum stramoniifolium Jacq. - a new potent source of
bioactive extracts rich in phenolic compounds for functional foods.
AB - Extracts prepared from leaves, roots, and stems of Solanum stramoniifolium Jacq.
(Solanaceae) in 80% ethanol have been tested for their in vitro antioxidant, anti
inflammatory, antimicrobial, and cytotoxic activities with an aim to find new
sources of substances for functional foods and food additives. The root extract
revealed the highest antioxidant activity in all assays exceeding the trolox
capacity, and was the only extract that inhibited nitric oxide production in
mouse macrophage cells, showing also the capacity to suppress the growth of all
tested human tumor cell lines (MCF-7, NCI-H460, HeLa and HepG2). The leaf extract
showed the strongest antimicrobial activity inhibiting all tested clinical
isolates. To the author's best knowledge it was the first time that all
individual parts of this plant were tested for biological activity together with
the phenolic compound characterization.
PMID- 28488720
TI - A dynamic strategy for wavelength sensing using the diffracted orders of a
grating.
AB - We propose a strategy for real time multicolour detection of light emitting
particles under flow conditions, using the diffracted orders of a grating. The
method relies on the fact that the spatial (angular/linear) separation between
the orders of a diffraction grating is a wavelength dependent quantity. Thus, the
difference in arrival times at a fixed detector for neighbouring orders produced
by a moving, light-emitting particle can be used as a wavelength sensing
mechanism. We demonstrate this functionality using a prototype PDMS microfluidic
device that incorporates a focusing transmission grating. A key attribute of this
approach is that it requires only a single sensitive detector, such as a
photomultiplier tube, in contrast to many conventional approaches which require
multiple sensitive detectors or a detector array.
PMID- 28488721
TI - Fluorinated cyclometalated iridium(iii) complexes as mitochondria-targeted
theranostic anticancer agents.
AB - Six cyclometalated iridium(iii) complexes bearing different numbers of fluorine
atoms were synthesized. These complexes demonstrated much better anti
proliferation activities towards five tumour cell lines than the widely used
clinical chemotherapeutic agent cisplatin. Moreover, the anti-proliferation
activities were correlated to the number of substituted fluorine atoms.
Colocalization and inductively coupled plasma-mass spectrometry (ICP-MS)
indicated that this series of complexes could penetrate cell membranes rapidly
and preferentially target mitochondria. Manifesting high selectivity between
tumour cells and normal cells and remarkable sensitivity to a cisplatin-resistant
cell line (A549R), complex Ir6 was successfully developed as a novel anticancer
agent (with IC50 values of 0.5 +/- 0.1 MUM for HeLa, 1.1 +/- 0.2 MUM for HepG2,
1.5 +/- 0.3 MUM for BEL-7402, 0.8 +/- 0.1 MUM for A549, and 0.7 +/- 0.2 MUM for
A549R cell lines). Further mechanism studies including mitochondrial membrane
potential depolarization and caspase 3/7 activation revealed that Ir6 induced
apoptosis via mitochondrial pathways. These results demonstrated that complex Ir6
might be a promising candidate as a mitochondria-targeted theranostic anticancer
agent.
PMID- 28488723
TI - Experimental observation of Shapiro-steps in colloidal monolayers driven across
time-dependent substrate potentials.
AB - We experimentally study the motion of a colloidal monolayer which is driven
across a commensurate substrate potential whose amplitude is periodically
modulated in time. In addition to a significant reduction of the static friction
force compared to an unmodulated substrate, we observe a Shapiro step structure
in the force dependence of the mean particle velocity which is explained by the
dynamical mode locking between the particle motion and the substrate modulation.
In this regime, the entire crystal moves in a stick-slip fashion similar to what
is observed when a single point contact is driven across a periodic surface.
Contrary to numerical simulations, where typically a large number of Shapiro
steps is found, only a single step is observed in our experiments. This is
explained by the formation of kinks which weaken the synchronization between
adjacent particles.
PMID- 28488724
TI - Complex effect of zinc oxide nanoparticles on cadmium chloride-induced
hepatotoxicity in mice: protective role of metallothionein.
AB - The wide range of applications of ZnO nanoparticles (nano ZnO) in commercial
products and the ubiquitous cadmium (Cd) contamination in the natural environment
increase the chance of co-existence of nano ZnO with Cd in the surroundings. To
investigate the effects of nano ZnO on CdCl2-induced hepatotoxicity in mice, the
histopathologic changes, metallothionein expression, oxidative stress responses
and serum biochemical parameters were determined after oral administration of
bulk or nano ZnO and/or CdCl2 for seven consecutive days. Bulk or nano ZnO had
low toxicity in mice. In contrast, CdCl2 led to significant hepatic oxidative
damage, as indicated by hepatic histopathological abnormalities and dysfunction.
Bulk and nano ZnO had nearly identical influences on the hepatotoxicity of CdCl2
in mice. Although co-administration of bulk or nano ZnO with CdCl2 had a positive
cooperative effect on the hepatic uptake of Cd and Zn, both bulk and nano ZnO
significantly attenuated CdCl2-caused hepatic damage via the reduction of
oxidative stress. The increase in metallothionein synthesis and the reduction of
Cd-induced perturbation of Zn2+ homeostasis after co-administration of bulk or
nano ZnO with CdCl2 play two important roles in the protective effect of bulk or
nano ZnO on CdCl2-caused hepatic oxidative damage.
PMID- 28488725
TI - A rare case of Marine-Lenhart syndrome with unilateral endocrine orbitopathy and
Hurthle cell carcinoma.
PMID- 28488726
TI - Prediction of renal cortical defect and scar using neutrophil-to-lymphocyte ratio
in children with febrile urinary tract infection.
AB - AIM: This study is aimed to evaluate the predictive value of the neutrophil-to
lymphocyte ratio (NLR) for cortical defect on initial and follow-up Tc-99m
dimercaptosuccinic acid (DMSA) scan in children with the first febrile urinary
tract infection (UTI). METHODS: We retrospectively enrolled 179 children with the
first febrile UTI who underwent DMSA scan and laboratory tests. In patients with
abnormal DMSA scan findings, follow-up DMSA scan was performed at least 6 months
after the initial scan. All DMSA scans were classified as negative and positive
cortical defects. Multiple logistic regression analyses were performed to
identify the risk factors for cortical defect on initial and follow-up DMSA scan.
RESULTS: Cortical defects on initial DMSA scan were noted in 133 patients.
Vesicoureteral reflux (VUR), white blood cell count, absolute neutrophil count,
NLR, and serum C-reactive protein level were independent predictive factors for
positive cortical defect on initial DMSA scan (p < 0.050). On follow-up DMSA
scan, 24 of the 133 patients showed persistent cortical defects, and only VUR was
significantly associated with persistent cortical defect (p = 0.002). In 84
patients who showed cortical defect on initial scan and absence of VUR, only NLR
was significantly associated with persistent cortical defect on follow-up scan (p
= 0.025). CONCLUSION: NLR was significantly associated with persistent cortical
defect on follow-up DMSA scan in patients without VUR, as well as positive
cortical defect on initial scan.
PMID- 28488727
TI - Differences in sodium fluoride-18 uptake in the normal skeleton depending on the
location and characteristics of the bone.
AB - AIM: The aim of this study was to evaluate the normal distribution of sodium
fluoride-18 (NaF-18) and to clarify the differences in uptake according to
location and the type of the bone using positron emission tomography (PET) /
computed tomography (CT). METHODS: We retrospectively reviewed NaF-18 PET/CT
images from 30 patients with hip joint disorders. PET/CT scans were performed 40
min after injection of approximately 185 MBq of NaF-18. To evaluate the
relationship between the distribution of NaF-18 uptake and bone density, we
compared the maximum standardised uptake values (SUVmax) on PET and the
Hounsfield Units (HUs) on CT of the lumbar vertebra, ilium, and proximal and
distal femurs. Regions of interests were defined both outside and inside the
cortical bone to measure whole bone and cancellous bone only, respectively.
RESULTS: The distribution of NaF-18 differed according to the skeletal site. The
lumbar vertebra showed the highest SUVmax for both whole bone and cancellous
bone, followed by the ilium, proximal femur, and distal femur. The bones differed
significantly in SUVmax. The distal femur showed the highest HU, followed by the
proximal femur, ilium, and vertebra. Profile curve analyses demonstrated that the
cancellous bones showed higher SUVmax and lower HU than the cortical bones.
CONCLUSIONS: Our results demonstrate the difference in NaF-18 uptake between
cancellous and cortical bones, which may explain differences in uptake by
location. NaF-18 uptake does not appear to be strongly correlated with bone
density, but rather with bone turnover and blood flow.
PMID- 28488728
TI - Fatty acid amide hydrolase (FAAH) regulates hypercapnia/ischemia-induced
increases in n-acylethanolamines in mouse brain.
AB - N-acylethanolamines (NAEs) are endogenous lipid ligands for several receptors
including cannabinoid receptors and peroxisome proliferator-activated receptor
alpha (PPAR-alpha), which regulate numerous physiological functions. Fatty acid
amide hydrolase (FAAH) is largely responsible for the degradation of NAEs.
However, at high concentrations of ethanolamines and unesterified fatty acids,
FAAH can also catalyze the reverse reaction, producing NAEs. Several brain
insults such as ischemia and hypoxia increase brain unesterified fatty acids.
Because FAAH can catalyze the synthesis of NAE, we aimed to test whether FAAH was
necessary for CO2 -induced hypercapnia/ischemia increases in NAE. To test this,
we examined levels of NAEs, 1- and 2-arachidonoylglycerols as well as their
corresponding fatty acid precursors in wild-type and mice lacking FAAH (FAAH-KO)
with three Kill methods: (i) head-focused, high-energy microwave irradiation
(microwave), (ii) 5 min CO2 followed by microwave irradiation (CO2 + microwave),
and (iii) 5 min CO2 only (CO2 ). Both CO2 -induced groups increased, to a similar
extent, brain levels of unesterified oleic, arachidonic, and docosahexaenoic acid
and 1- and 2-arachidonoylglycerols compared to the microwave group in both wild
type and FAAH-KO mice. Oleoylethanolamide (OEA), arachidonoylethanolamide (AEA),
and docosahexaenoylethanolamide (DHEA) levels were about 8-, 7-, and 2.5-fold
higher, respectively, in the FAAH-KO mice compared with the wild-type mice.
Interestingly, the concentrations of OEA, AEA, and DHEA increased 2.5- to 4-fold
in response to both CO2 -induced groups in wild-type mice, but DHEA increased
only in the CO2 group in FAAH-KO mice. Our study demonstrates that FAAH is
necessary for CO2 - induced increases in OEA and AEA but not DHEA. Targeting
brain FAAH could impair the production of NAEs in response to brain injuries.
PMID- 28488729
TI - Randomized clinical trial of biodegradeable intraluminal sheath to prevent
anastomotic leak after stapled colorectal anastomosis.
AB - BACKGROUND: Anastomotic leakage is a potential major complication after
colorectal surgery. The C-seal was developed to help reduce the clinical leakage
rate. It is an intraluminal sheath that is stapled proximal to a colorectal
anastomosis, covering it intraluminally and thus preventing intestinal leakage in
case of anastomotic dehiscence. The C-seal trial was initiated to evaluate the
efficacy of the C-seal in reducing anastomotic leakage in stapled colorectal
anastomoses. METHODS: This RCT was performed in 41 hospitals in the Netherlands,
Germany, France, Hungary and Spain. Patients undergoing elective surgery with a
stapled colorectal anastomosis less than 15 cm from the anal verge were eligible.
Included patients were randomized to the C-seal and control groups, stratified
for centre, anastomotic height and intention to create a defunctioning stoma.
Primary outcome was anastomotic leakage requiring invasive treatment. RESULTS:
Between December 2011 and December 2013, 402 patients were included in the trial,
202 in the C-seal group and 200 in the control group. Anastomotic leakage was
diagnosed in 31 patients (7.7 per cent), with a 10.4 per cent leak rate in the C
seal group and 5.0 per cent in the control group (P = 0.060). Male sex showed a
trend towards a higher leak rate (P = 0.055). Construction of a defunctioning
stoma led to a lower leakage rate, although this was not significant (P = 0.095).
CONCLUSION: C-seal application in stapled colorectal anastomoses does not reduce
anastomotic leakage. Registration number: NTR3080
(http://www.trialregister.nl/trialreg/index.asp).
PMID- 28488730
TI - Octreotide-Associated Neutropenia.
AB - Drug-induced neutropenia and agranulocytosis are rare adverse events but can be
fatal. Neutropenia can be induced by a myriad of drugs from almost every
pharmacologic class. Octreotide is a somatostatin analog that has been used to
treat variceal bleeding, acromegaly, and severe diarrhea associated with
metastatic tumors, and to reduce symptoms in the setting of malignant bowel
obstruction and pseudoobstruction. The most common adverse effects associated
with octreotide include pain at the injection site and gastrointestinal effects
such as loose stools, cramping, and nausea; neutropenia is not currently listed
as an adverse effect of the drug. We describe the case of an 87-year-old man who
developed neutropenia immediately after administration of three doses of
subcutaneous octreotide. He presented to the hospital with a history of
constipation and straining for 3 days. He was admitted, and laxatives,
suppositories, and enemas were administered over the next 3 days to induce a
bowel movement; however, they were ineffective. Bowel obstruction secondary to a
mass was confirmed by computed tomography; the mass was eventually diagnosed as
colon cancer. Octreotide 100 ug subcutaneously every 8 hours was started for the
obstruction on the evening of hospital day 4. After the patient had received 3
doses of octreotide, his white blood cell count (WBC) had decreased from 4.1 *
103 /mm3 (neutrophils 75.4%, absolute neutrophil count [ANC] 3.1 * 103 /mm3 ) on
admission to 1.6 * 103 /mm3 (neutrophils 62%, ANC 0.99 * 103 /mm3 ) on day 5.
Given the temporal relationship of octreotide and neutropenia as well as the lack
of a reasonable alternative cause, it was suspected that octreotide was the most
likely culprit of the patient's neutropenia. Octreotide was subsequently
discontinued, and his WBC increased to 4.9 * 103 /mm3 (neutrophils 66.3%, ANC 3.2
* 103 /mm3 ) the next day. The remainder of the patient's hospitalization was not
significant for any further hematologic abnormalities. His WBC and ANC (WBC 6.7 *
103 /mm3 , neutrophils 83.2%, ANC 5.6 * 103 /mm3 ) remained stable 30 days after
the incident. Use of the Naranjo Adverse Drug Reaction Probability Scale
indicated a probable relationship (score of 5) between the patient's development
of neutropenia and octreotide therapy. To our knowledge, this report highlights
the first case of octreotide-associated neutropenia. Although the frequency of
drug-induced neutropenia remains rare outside of cytotoxic chemotherapy, the
importance of recognizing this adverse effect cannot be understated given the
mortality risks for neutropenic patients.
PMID- 28488731
TI - Development of a rectal sexually transmitted infection (STI) Model in Rhesus
macaques using Chlamydia trachomatis serovars E and L2.
AB - BACKGROUND: Rectal STI coinfection models enhance the understanding of rectal HIV
transmission risk factors. MATERIALS AND METHODS: Rhesus macaques (n=9) were
exposed to one of three rectal Chlamydia trachomatis (CT) challenges: C.
trachomatis L2 (CT-L2 ); C. trachomatis serovar E (CT-E), followed by CT-L2 ; or
CT-E, treatment/clearance, then CT-L2 . Infections were monitored by PCR. Weekly
blood and rectal secretion/lavage samples were collected for cytokine analyzes
and/or epithelial sloughing, occult, and overt blood determinations. RESULTS:
Chlamydial infections were successfully established in each animal, with varying
degrees of persistence. Mucosal IL-1beta was upregulated in animals consecutively
infected with CT-E then CT-L2 (P=.05). Epithelial sloughing was also
significantly increased post-infection in this group (P=.0003). CONCLUSIONS: This
study demonstrates successful rectal infection of rhesus macaques with CT-E and
CT-L2 and describes measures of assessing rectal inflammation and pathology.
Different infection strategies yield varying inflammatory and pathologic
outcomes, providing well-described models for future SIV/SHIV susceptibility
studies.
PMID- 28488732
TI - Involvement of the Warburg effect in non-tumor diseases processes.
AB - Warburg effect, as an energy shift from mitochondrial oxidative phosphorylation
to aerobic glycolysis, is extensively found in various cancers. Interestingly,
increasing researchers show that Warburg effect plays a crucial role in non-tumor
diseases. For instance, inhibition of Warburg effect can alleviate pulmonary
vascular remodeling in the process of pulmonary hypertension (PH). Interference
of Warburg effect improves mitochondrial function and cardiac function in the
process of cardiac hypertrophy and heart failure. Additionally, the Warburg
effect induces vascular smooth muscle cell proliferation and contributes to
atherosclerosis. Warburg effect may also involve in axonal damage and neuronal
death, which are related with multiple sclerosis. Furthermore, Warburg effect
significantly promotes cell proliferation and cyst expansion in polycystic kidney
disease (PKD). Besides, Warburg effect relieves amyloid beta-mediated cell death
in Alzheimer's disease. And Warburg effect also improves the mycobacterium
tuberculosis infection. Finally, we also introduce some glycolytic agonists. This
review focuses on the newest researches about the role of Warburg effect in non
tumor diseases, including PH, tuberculosis, idiopathic pulmonary fibrosis (IPF),
failing heart, cardiac hypertrophy, atherosclerosis, Alzheimer's diseases,
multiple sclerosis, and PKD. Obviously, Warburg effect may be a potential
therapeutic target for those non-tumor diseases.
PMID- 28488733
TI - Surgical resection for Bismuth type IV perihilar cholangiocarcinoma.
AB - BACKGROUND: Bismuth type IV perihilar cholangiocarcinoma has traditionally been
categorized as unresectable disease. The aim of this study was to review
experience with a resection-based strategy in patients who have type IV perihilar
cholangiocarcinoma. METHODS: Medical records of consecutive patients with a
diagnosis of type IV perihilar cholangiocarcinoma between 2006 and 2015 were
reviewed retrospectively. Primary outcomes assessed were surgical results and
long-term survival. RESULTS: Of the 332 patients with type IV tumour, 216 (65.1
per cent) underwent resection. Left hepatic trisectionectomy was the most common
procedure (112 patients). Combined vascular resection was performed in 131
patients. Median duration of operation was 607 (range 356-1045) min, and blood
loss was 1357 (209-10 349) ml. Complications of Clavien-Dindo grade III or more
developed in 90 patients (41.7 per cent) and four (1.9 per cent) died from
complications within 90 days. Survival rates were better for the 216 patients
whose tumours were resected than for the 116 patients with unresected tumours
(32.8 versus 1.5 per cent at 5 years; P < 0.001). Patients with pN0 M0 disease
after resection had a favourable 5-year survival rate of 53 per cent.
Percutaneous transhepatic biliary drainage, blood transfusion, lymph node
metastasis and distant metastasis were identified as independent negative
prognostic factors for survival. CONCLUSION: Although resection for type IV
tumour is technically demanding with high morbidity, it can be performed with low
mortality and offers better survival probability in selected patients.
PMID- 28488734
TI - Body Size and the Risk of Primary Hyperparathyroidism in Women: A Cohort Study.
AB - Greater body weight and fat mass have been associated with higher serum
parathyroid hormone levels and a higher prevalence of primary hyperparathyroidism
(P-HPTH) in women. However, prospective studies to evaluate whether greater body
size associates with a higher incidence of developing P-HPTH have not been
reported. We investigated whether greater body size was independently associated
with a higher risk for developing P-HPTH in women. We conducted a prospective
cohort study of 85,013 female participants in the Nurses' Health Study I followed
for up to 26 years. Body size was measured via multiple metrics: weight, body
mass index (BMI), and waist circumference (WC). Weight and BMI were assessed
every 2 years from 1986 to 2012, and WC was assessed in 1986, 1996, and 2000.
Detailed dietary and demographic exposures were quantified via validated biennial
questionnaires. Incident cases of P-HPTH were confirmed by individual medical
record review. Cox proportional hazards models were used to evaluate whether WC,
weight, and BMI were independent risk factors for developing P-HPTH. Models were
adjusted for demographic variables, comorbidities, medications, intakes of
calcium and vitamin D, and exposure to ultraviolet light. We confirmed 491
incident cases of P-HPTH during 2,128,068 person-years of follow-up. The
multivariable-adjusted relative risks for incident P-HPTH increased across
quartiles of WC: Q1, ref; Q2, 1.34 (0.97, 1.86); Q3, 1.70 (1.24, 2.31); Q4, 2.27
(1.63, 3.18); p trend < 0.001. Similarly, the multivariable-adjusted risks for
incident P-HPTH increased across quartiles of weight: Q1, ref; Q2, 1.23 (0.92,
1.65); Q3, 1.63 (1.24, 2.14); Q4, 1.65 (1.24, 2.19); p trend < 0.001. A similar
but statistically non-significant trend was observed across quartiles of BMI (p
trend = 0.07). In summary, body size may be an independent and modifiable risk
factor for developing P-HPTH in women. (c) 2017 American Society for Bone and
Mineral Research.
PMID- 28488735
TI - TERMITE: An R script for fast reduction of laser ablation inductively coupled
plasma mass spectrometry data and its application to trace element measurements.
AB - RATIONALE: High spatial resolution Laser Ablation Inductively Coupled Plasma Mass
Spectrometry (LA-ICPMS) determination of trace element concentrations is of great
interest for geological and environmental studies. Data reduction is a very
important aspect of LA-ICP-MS, and several commercial programs for handling LA
ICPMS trace element data are available. Each of these software packages has its
specific advantages and disadvantages. METHODS: Here we present TERMITE, an R
script for the reduction of LA-ICPMS data, which can reduce both spot and line
scan measurements. Several parameters can be adjusted by the user, who does not
necessarily need prior knowledge in R. Currently, ten reference materials with
different matrices for calibration of LA-ICPMS data are implemented, and
additional reference materials can be added by the user. TERMITE also provides an
optional outlier test, and the results are provided graphically (as a pdf file)
as well as numerically (as a csv file). RESULTS: As an example, we apply TERMITE
to a speleothem sample and compare the results with those obtained using the
commercial software GLITTER. The two programs give similar results. TERMITE is
particularly useful for samples that are homogeneous with respect to their major
element composition (in particular for the element used as an internal standard)
and when many measurements are performed using the same analytical parameters. In
this case, data evaluation using TERMITE is much faster than with all other
available software, and the concentrations of more than 100 single spot
measurements can be calculated in less than a minute. CONCLUSIONS: TERMITE is an
open-source software for the reduction of LA-ICPMS data, which is particularly
useful for the fast, reproducible evaluation of large datasets of samples that
are homogeneous with respect to their major element composition. Copyright (c)
2017 John Wiley & Sons, Ltd.
PMID- 28488736
TI - Inhibition of mTOR pathway decreases the expression of pre-meiotic and meiotic
markers throughout postnatal development and in adult testes in mice.
AB - Rapamycin (mTOR inhibitor) has been reported to have negative effect on human
male gonadal function. Previously, we showed that mTOR signalling molecules are
expressed during early spermatogenesis in mice. The objective of this study was
to investigate the role of mTOR signalling in meiosis both during the first wave
of spermatogenesis and also during adult spermatogenesis. Day 5 post-partum mice
were administered rapamycin and retinoic acid (RA; a Stra8 activator), and
expression of p-p70S6K and Stra8 proteins was evaluated. p-p70S6K and Stra8
protein expressions decreased in post-natal testes after rapamycin treatment.
Stra8 protein expression increased after RA and rapamycin+RA administrations in
post-natal testes. In adult mice, rapamycin was administrated for 1 or 4 weeks.
Morphological analysis for testicular damage and TUNEL assay was performed. After
rapamycin administration, germ cell loss increased in adult testes.
Ultrastructural analysis revealed disorganised testicular morphology and
vacuolisation. The number of apoptotic germ cells increased after 4 weeks
rapamycin administration. Stra8 and Dmc1 expressions decreased in 4 weeks
rapamycin group, whereas Sycp3 and VASA expression did not change. Our findings
suggest that mTOR pathway has an important role in meiotic progress of male germ
cells both during first wave of spermatogenesis and in adult mice.
PMID- 28488737
TI - Angiotensin II signalling kicks out p27Kip1 : casein kinase 2 augmentation of Cav
1.2 L-type Ca2+ channel activity in immature ventricular cardiomyocytes.
PMID- 28488738
TI - Comparison of three different extenders on Murrah buffaloes (Bubalus bubalis)
semen freezability.
AB - The use of frozen semen for artificial insemination is the main approach utilised
for the genetic improvement of most domesticated species. The advantages include
lower transportation costs, continuous availability of semen, fewer occurrences
of sexually transmitted diseases and the incorporation of desirable genes in a
relatively short amount of time. Nevertheless, the use of frozen semen in buffalo
herds remains limited due to the loss of sperm quality when buffalo semen is
frozen. So, the goal of this study was to evaluate the pre- and post
cryopreservation quality of buffalo semen diluted in three distinct freezing
media: Tris-egg yolk, Botu-bov(r) (BB) and ACP-111(r). Thirty-two ejaculates from
four bulls were analysed in terms of kinetics, morphology and sperm viability by
epifluorescence microscope. Thawed samples were also evaluated for capacitation
like damage, DNA fragmentation and plasma and acrosomal membrane integrity using
flow cytometry. The Tris-egg yolk and BB(r) extenders yielded better results than
the ACP-111(r) extender for kinetics parameter (total motility, progressive
motility and percentage of rapid cells). However, semen samples were similar for
parameters evaluated by flow cytometry. Taken together, the data indicate that in
comparison with Tris-egg yolk and BB extender, ACP-111(r) can also be used as an
extender for buffalo semen cryopreservation.
PMID- 28488739
TI - Reducing contamination parameters for clumped isotope analysis: The effect of
lowering PorapakTM Q trap temperature to below -50 degrees C.
AB - RATIONALE: Carbonate clumped isotope thermometry examines the thermodynamic
preference of 13 C-18 O bonds to form within the carbonate crystal lattice. The
13 C18 O16 O isotopologue in analyte CO2 has a natural abundance of 44.4 ppm
necessitating stringent purification procedures to remove contaminant molecules
that may produce significant isobaric effects within range of the mass 47
isotopologue. Strict purifications of analyte CO2 are thus required as well as
reliable contamination indicators. METHODS: CO2 purification was carried out by
vacuum cryogenic purification through a static trap packed with PorapakTM Q
(PPQ). The correlation between mass excesses on m/z 47, 48 and 49 in CO2 produced
by acid digestion of 12 natural samples was measured by isotope ratio mass
spectrometry (IRMS). CO2 from two contaminated carbonate samples was then
purified at PPQ trap temperatures between -25 and -65 degrees C and measured by
IRMS to determine changes in mass excesses on m/z 47, 48 and 49. Finally
carbonate standards, Carrara marble (CM) and ETH3, were purified at PPQ trap
temperatures of -35 and -60 degrees C to identify isotopic fractionation
associated with lowering trap temperature. RESULTS: The correlation between mass
excesses on m/z 47, 48 and 49 is determined to be sample dependent. Lowering the
PPQ trap temperature to -60 degrees C has a 78% success rate in decreasing
Delta48offset , a measure of sample contamination, to within an acceptable range
(<1.5 0/00). Lowering the PPQ temperature in purification of CM and ETH3 is
associated with decreases in the delta13 C and delta18 O values as a result of
isotopic fractionation. We demonstrate that we can correct for fractionation at a
trap temperature of -60 degrees C. CONCLUSIONS: Lowering the temperature of the
Porapak Q trap to -60 degrees C results in improved sample cleaning. It is
possible to correct for fractionation in delta13 C and delta18 O values at lower
PPQ trap temperatures using identically prepared standards. This result has
important connotations for laboratories using similar sample preparation methods.
PMID- 28488740
TI - Ethanol-induced mitophagy in rat Sertoli cells: Implications for male fertility.
AB - Autophagy is a pro-survival mechanism involving lysosomal degradation of damaged
cellular components following multiple forms of cellular stress. There is
currently a lack of literature on the mechanism, and specifically on mitophagy
(selective autophagy of damaged pro-apoptotic mitochondria) in Sertoli cells
(SCs). Against such a background, the authors induced mitophagy in SCs of adult
male rats using a single injection of ethanol (5 g/kg) and observed mitophagy in
the SCs via transmission electron microscopy 24 hr later. In addition, we briefly
discussed the possible clinical implications of enhanced autophagy and mitophagy
in stressed SCs in our model and in other models of acute stress (e.g., heat and
transplantation stress). Further studies on SC autophagy are required, as a full
understanding of the molecular mechanisms controlling autophagy in stressed SCs
may have therapeutic implications for infertility treatment.
PMID- 28488741
TI - Cancer screening is not only about numbers.
AB - In the cancer screening debate, arguments for and against screening are often
based on statistics, whereas for individuals personal, non-statistical factors
are at least as important when deciding whether to participate in screening.
Health care professionals have a responsibility in helping individuals navigate
in this complex field by identifying and clarifying the individuals' beliefs,
fears and preferences while being aware of their own. Moreover, researchers
should explore beliefs and motives that matter for individuals and not only
report numbers that can be interpreted in different ways.
PMID- 28488742
TI - Feminization of the fat distribution pattern of children and adolescents in a
recent German population.
AB - OBJECTIVES: During the early 1990s, the economic and political situation in
eastern Germany changed overnight. Here, we use the rare chance of an experiment
like setting in humans and aim to test whether the rapid change of environmental
conditions in eastern Germany in the 1990s led to a change in the sex-specific
fat distribution pattern, an endocrine-influenced phenotypic marker. METHODS:
Based on a cross-sectional data set of 6- to 18-year-old girls and boys measured
between 1982-1991 and 1997-2012, we calculated a skinfold ratio of triceps to
subscapular and percentage of body fat. Using linear regressions, we tested for
differences in percentage of body fat and skinfold ratio between these two time
periods. RESULTS: We found that the percentage of body fat increased in boys and
girls, and they accumulated relatively more fat on extremities than on the trunk
in all BMI groups measured after 1997 as compared to those measured between 1982
and 1991. CONCLUSIONS: Concurrent with drastic and rapid changes of environmental
conditions, the body fat distribution of children and adolescents changed to a
more feminized pattern during the early 1990s in an East German population. The
changes in this endocrinologically mediated pattern might be associated with the
increased exposure of individuals to endocrine-disrupting chemicals which are
known to influence the endocrine, reproductive, and immune systems in animals and
humans.
PMID- 28488743
TI - Photoisomerization of Bis(tridentate) 2,6-Bis(1H-pyrazol-1-yl)pyridine Ligands
Exhibiting a Multi-anthracene Skeleton.
AB - A novel molecular design is described where two peripheral moieties made of 2,6
bis(1H-pyrazol-1-yl)pyridine are linked through multi-1,8-diethynylanthracene
moieties. The optimized synthesis of the three isostructural analogues 1 a, 1 b,
and 1 c, containing the anthraquinone, anthracene, and 10-methoxyanthracene
units, respectively, is reported. The resulting spatial face-to-face arrangement
of the peripheral anthracene rings enables to trigger the intramolecular [4+4]
photocycloaddition affording the isomers P1 b and P1 c, which can be thermally
cleaved back to the original anthracene derivatives 1 b and 1 c, respectively.
Single-crystal X-ray diffraction studies confirm the expected molecular
structures of compounds 1 a-1 c as well as of their corresponding isomers P1 b
and P1 c. The spectral, optical, and electrochemical properties of all
synthesized compounds are investigated and discussed.
PMID- 28488744
TI - Membrane vesicle secretion and prophage induction in multidrug-resistant
Stenotrophomonas maltophilia in response to ciprofloxacin stress.
AB - Several bacterial species produce membrane vesicles (MVs) in response to
antibiotic stress. However, the biogenesis and role of MVs in bacterial
antibiotic resistance mechanisms have remained unclear. Here, we studied the
effect of the fluoroquinolone ciprofloxacin on MV secretion by Stenotrophomonas
maltophilia using a combination of electron microscopy and proteomic approaches.
We found that in addition to the classical outer membrane vesicles (OMV),
ciprofloxacin-stimulated cultures produced larger vesicles containing both outer
and inner membranes termed outer-inner membrane vesicles (OIMV), and that such
MVs are enriched with cytosolic proteins. Remarkably, OIMV were found to be
decorated with filamentous structures identified as fimbriae. In addition,
ciprofloxacin stress leads to the release of bacteriophages and phage tail-like
particles. Prophage induction by ciprofloxacin has been linked to pathogenesis
and horizontal gene transfer in several bacterial species. Together, our findings
show that ciprofloxacin treatment of S. maltophilia leads to the secretion of a
heterogeneous pool of MVs and the induction of prophages that are potentially
involved in adverse side-effects during antibiotic treatment.
PMID- 28488745
TI - The 2-week wait and other initiatives to improve cancer diagnosis: Has it altered
survival? The answer is unclear-the evidence is too weak.
AB - The UK is one of the lowest ranked high-income countries for cancer survival.
Later stage at diagnosis is a significant contributor to reduced survival.
Several strategies have been introduced to reduce delays in an effort to diagnose
cancer earlier. This commentary summarises the evidence and impact of these
initiatives.
PMID- 28488747
TI - Ultra-performance liquid chromatography/multiple reaction monitoring mass
spectrometry quantification of trastuzumab in human serum by selective monitoring
of a specific peptide marker from the antibody complementarity-determining
regions.
AB - RATIONALE: Because of the large molecular weight, the structural complexity and
the similarity with endogenous immunoglobulins present in high concentrations, in
vivo quantitative studies with therapeutic monoclonal antibodies are particularly
challenging. In this work, an UPLC/MRM MS-based methodology is described for the
quantification of trastuzumab in human serum by monitoring a novel specific
peptide marker located within its heavy chain Complementarity-Determining Region
(CDR). METHODS: For maximum sensitivity and selectivity, specific transitions of
this diagnostic proteotypic peptide were optimized and monitored at m/z 364.1 ->
437.3 (quantitation ion) and m/z 364.1 -> 358.0 (confirmation ion). As a proof-of
concept, the methodology was applied to the determination of trastuzumab in human
serum over a clinically relevant range from 0.02 to 200 MUg/mL. The methodology
has been evaluated in terms of specificity, linearity, accuracy, precision,
detection and quantitation limits. RESULTS: An excellent linear response has been
obtained in the range from 0.036 to 3.6 fmol/MUL for the standard peptide and
from 0.03 to 285 fmol/MUL for the trastuzumab in human serum with typical R2
values of 0.99. The limit of detection (LOD) and limit of quantification (LOQ)
are 0.005 fmol/MUL and 0.05 fmol/MUL, respectively, with mean bias and RSD values
of 18% and 1%, respectively, for quality control samples. CONCLUSIONS: The
strategy used to set up the UPLC/MRM MS methodology based on monitoring specific
peptide markers within CDRs can be potentially applied to the detection and
quantification of other humanized or human mAbs in biological fluids. Copyright
(c) 2017 John Wiley & Sons, Ltd.
PMID- 28488748
TI - Formation of Double-Shelled Zinc-Cobalt Sulfide Dodecahedral Cages from
Bimetallic Zeolitic Imidazolate Frameworks for Hybrid Supercapacitors.
AB - Complex metal-organic frameworks used as precursors allow design and construction
of various nanostructured functional materials which might not be accessible by
other methods. Here, we develop a sequential chemical etching and sulfurization
strategy to prepare well-defined double-shelled zinc-cobalt sulfide (Zn-Co-S)
rhombic dodecahedral cages (RDCs). Yolk-shelled zinc/cobalt-based zeolitic
imidazolate framework (Zn/Co-ZIF) RDCs are first synthesized by a controlled
chemical etching process, followed by a hydrothermal sulfurization reaction to
prepare double-shelled Zn-Co-S RDCs. Moreover, the strategy reported in this work
enables easy control of the Zn/Co molar ratio in the obtained double-shelled Zn
Co-S RDCs. Owing to the structural and compositional benefits, the obtained
double-shelled Zn-Co-S RDCs exhibit enhanced performance with high specific
capacitance (1266 F g-1 at 1 A g-1 ), good rate capability and long-term cycling
stability (91 % retention over 10,000 cycles) as a battery-type electrode
material for hybrid supercapacitors.
PMID- 28488749
TI - How are we assessing the safety and quality use of medicines used by young people
in Australia?
PMID- 28488750
TI - Computing the Extended Synthesis: Mapping the Dynamics and Conceptual Structure
of the Evolvability Research Front.
AB - Since the late 1970s, the field of evolutionary biology has undergone empirical
and theoretical developments that have threaten the pillars of evolutionary
theory. Some evolutionary biologists have recently argued that evolutionary
biology is not experiencing a paradigm shift, but an expansion of the modern
synthesis. Philosophers of biology focusing on scientific practices seem to agree
with this pluralistic interpretation and have argued that evolutionary theory
should rather be seen as an organized network of multiple problem agendas with
diverse disciplinary contributors. In this paper, I apply a computational
analysis to study the dynamics and conceptual structure of one of the main
emerging problem agendas in evolutionary biology: evolvability. I have used
CiteSpace, an application for visualizing and analyzing trends and patterns in
scientific literature that applies cocitation analysis to identify scientific
specialities. I analyze the main clusters of the evolvability cocitation network
with the aim to identify the main research lines and the interdisciplinary
relationships that structure this research front. I then compare these results
with the existing classifications of evolvability concepts, and identify four
main conceptual tensions within the definitions of evolvability. Finally, I argue
that there is a lot of usefulness in the inconsistency in which the term
evolvability is used in biological research. I claim that evolvability research
has set up "trading zones" in biology that make possible interdisciplinary
exchanges.
PMID- 28488751
TI - Consistent Infection Prevention: Vital During Routine and Emerging Infectious
Diseases Care
PMID- 28488752
TI - Functional structure of the bromeliad tank microbiome is strongly shaped by local
geochemical conditions.
AB - Phytotelmata in tank-forming Bromeliaceae plants are regarded as potential
miniature models for aquatic ecology, but detailed investigations of their
microbial communities are rare. Hence, the biogeochemistry in bromeliad tanks
remains poorly understood. Here we investigate the structure of bacterial and
archaeal communities inhabiting the detritus within the tanks of two bromeliad
species, Aechmea nudicaulis and Neoregelia cruenta, from a Brazilian sand dune
forest. We used metagenomic sequencing for functional community profiling and 16S
sequencing for taxonomic profiling. We estimated the correlation between
functional groups and various environmental variables, and compared communities
between bromeliad species. In all bromeliads, microbial communities spanned a
metabolic network adapted to oxygen-limited conditions, including all
denitrification steps, ammonification, sulfate respiration, methanogenesis,
reductive acetogenesis and anoxygenic phototrophy. Overall, CO2 reducers
dominated in abundance over sulfate reducers, and anoxygenic phototrophs largely
outnumbered oxygenic photoautotrophs. Functional community structure correlated
strongly with environmental variables, between and within a single bromeliad
species. Methanogens and reductive acetogens correlated with detrital volume and
canopy coverage, and exhibited higher relative abundances in N. cruenta. A
comparison of bromeliads to freshwater lake sediments and soil from around the
world, revealed stark differences in terms of taxonomic as well as functional
microbial community structure.
PMID- 28488753
TI - Cascades of Interrupted Pummerer Reaction-Sigmatropic Rearrangement.
AB - A new class of Pummerer chemistry has emerged as a powerful tool in organic
synthesis. The new technology consists of a beautiful cascade of an interrupted
Pummerer reaction and the subsequent [3,3] sigmatropic rearrangement. The
interrupted Pummerer reactions of alkenyl or aryl sulfoxides with unsaturated
nucleophiles such as allylic silanes, ketones, and phenols provide sulfonium
intermediates, which are ready to undergo smooth charge-accelerated [3,3]
sigmatropic rearrangement with excellent to exclusive regioselectivity. Some of
the transformations proceed with transient loss of aromaticity. The reactions
afforded five-membered heterocycles, benzofurans, and biaryls of importance,
depending on the sulfoxides and nucleophiles used. The reactions are unique and
game-changing because they are efficient, robust, redox-neutral, regioselective,
and metal-free, which perfectly fits the need of modern organic synthesis. This
chemistry also underscores the synthetic potential of organosulfur chemistry.
PMID- 28488754
TI - Virtual endovascular treatment of intracranial aneurysms: models and uncertainty.
AB - Virtual endovascular treatment models (VETMs) have been developed with the view
to aid interventional neuroradiologists and neurosurgeons to pre-operatively
analyze the comparative efficacy and safety of endovascular treatments for
intracranial aneurysms. Based on the current state of VETMs in aneurysm rupture
risk stratification and in patient-specific prediction of treatment outcomes, we
argue there is a need to go beyond personalized biomechanical flow modeling
assuming deterministic parameters and error-free measurements. The
mechanobiological effects associated with blood clot formation are important
factors in therapeutic decision making and models of post-treatment intra
aneurysmal biology and biochemistry should be linked to the purely hemodynamic
models to improve the predictive power of current VETMs. The influence of model
and parameter uncertainties associated to each component of a VETM is, where
feasible, quantified via a random-effects meta-analysis of the literature. This
allows estimating the pooled effect size of these uncertainties on aneurysmal
wall shear stress. From such meta-analyses, two main sources of uncertainty
emerge where research efforts have so far been limited: (1) vascular wall
distensibility, and (2) intra/intersubject systemic flow variations. In the
future, we suggest that current deterministic computational simulations need to
be extended with strategies for uncertainty mitigation, uncertainty exploration,
and sensitivity reduction techniques. WIREs Syst Biol Med 2017, 9:e1385. doi:
10.1002/wsbm.1385 For further resources related to this article, please visit the
WIREs website.
PMID- 28488755
TI - Frequency-Dependent Habituation Deficit of the Nociceptive Blink Reflex in Aura
With Migraine Headache. Can Migraine Aura Modulate Trigeminal Excitability?
AB - OBJECTIVE: To study the influence of the migraine aura on the trigeminal
nociception, we investigated the habituation of the nociceptive blink reflex
(nBR) R2 responses in aura with migraine headache (AwMH) and comparatively in
migraine without aura (MWoA) and healthy subjects (HS). BACKGROUND: A clear
deficit of habituation in trigeminal nociceptive responses has been documented in
MWoA; however, similar data in MWA are lacking. METHODS: Seventeen AwMH, 29 MWoA,
and 30 HS were enrolled and a nonrandomized clinical neurophysiological study
examining nBR habituation by clinical diagnosis was devised. We delivered a
series of 26 electrical stimuli, at different stimulation frequencies (SF) (0.05,
0.1, 0.2, 0.3, 0.5, and 1 Hz), subsequently subdivided in five blocks of five
responses for each SF. The mean area values of the second to the fifth block
expressed as the percentage of the mean area value of the first block were taken
as an index of habituation for each SF. RESULTS: A significant lower mean
percentage decrease of the R2 area across all blocks was found at 1, 0.5, 0.3,
and 0.2 Hz SF in MWoA and at 0.3 and 0.2 Hz SF in AwMH, when compared to HS. In
the most representative fifth block of responses, we found in MWoA vs HS at 1 Hz,
57.0 +/- 27.8 vs 30.6 +/- 12.0; at 0.5 Hz, 54.8 +/- 26.1 vs 32.51 +/- 17.7; at
0.3 Hz, 44.7 +/- 21.6 vs 27.6 +/- 13.2; at 0.2 Hz, 61.3 +/- 29.5 vs 32.6 +/-
18.0, and in AwMH vs HS at 0.3 Hz, 52.7 +/- 24.7 vs 27.6 +/- 13.2; at 0.2 Hz,
69.3 +/- 38.6 vs 32.6 +/- 18.0 as mean +/- SD of the R2 area percentage of the
first block, respectively. Interestingly, AwMH subjects did not show differences
in mean percentage decrease of the R2 area at 1 and 0.5 Hz SF when compared to
HS. No differences between groups were found at 0.1 and 0.05 Hz SF. CONCLUSIONS:
We demonstrated in AwMH a deficit of habituation of the nBR R2 responses after
repeated stimulations, although less pronounced than that observed in MWoA of
comparable clinical severity. We hypothesize that AwMH and MWoA share some
pathogenetic aspects, and also that migraine aura physiopathology may play a
modulating role on the excitability of the nociceptive trigeminal pathways.
PMID- 28488756
TI - Cyclic Vomiting Syndrome in Adults and Children: A Hypothesis.
AB - OBJECTIVE: To see how patients' clinical descriptions compare to the third
classification of International Classification of Headache Disorders (ICHD-III
beta). BACKGROUND: CVS is an episodic syndrome associated with migraine. It is a
rare disorder of childhood and adulthood. New criteria are proposed in the third
classification of International Classification of Headache Disorders. METHODS:
This study describes children and adults' CVS characteristics at a French
tertiary-care center, according to the ICHD-II and ICHD-III beta criteria.
Clinical features, and results of paraclinical tests were characterized. RESULTS:
Fifteen patients were included: 8 adults, 2 children, and 5 adolescents. Familial
history of migraine or CVS was respectively noticed in 12 and 4 patients. The
duration of premonitory, emetic, and postdromal phases was evaluated from hours
to days. Some symptoms described in theses phases are also described in
migrainous population, with a comparable frequency. Cranial or systemic autonomic
symptoms were respectively reported in 47% and 93%. Nine patients described a
circadian periodicity, and six patients described a circannual periodicity. The
predictable periodicity was from 1 week to 12 months. A brain perfusion SPECT
showed an increased hypothalamic perfusion during emetic phase in one patient.
CONCLUSIONS: CVS is a rare episodic syndrome associated with migraine. Some
clinical features and paraclincal tests suggest a chronobiological disease.
PMID- 28488757
TI - Stimulation of Pol III-dependent 5S rRNA and U6 snRNA gene expression by AP-1
transcription factors.
AB - RNA polymerase III transcribes structurally diverse group of essential noncoding
RNAs including 5S ribosomal RNA (5SrRNA) and U6 snRNA. These noncoding RNAs are
involved in RNA processing and ribosome biogenesis, thus, coupling Pol III
activity to the rate of protein synthesis, cell growth, and proliferation. Even
though a few Pol II-associated transcription factors have been reported to
participate in Pol III-dependent transcription, its activation by activator
protein 1 (AP-1) factors, c-Fos and c-Jun, has remained unexplored. Here, we show
that c-Fos and c-Jun bind to specific sites in the regulatory regions of 5S rRNA
(type I) and U6 snRNA (type III) gene promoters and stimulate their
transcription. Our chromatin immunoprecipitation studies suggested that
endogenous AP-1 factors bind to their cognate promoter elements during the G1/S
transition of cell cycle apparently synchronous with Pol III transcriptional
activity. Furthermore, the interaction of c-Jun with histone acetyltransferase
p300 promoted the recruitment of p300/CBP complex on the promoters and
facilitated the occupancy of Pol III transcriptional machinery via histone
acetylation and chromatin remodeling. The findings of our study, together,
suggest that AP-1 factors are novel regulators of Pol III-driven 5S rRNA and U6
snRNA expression with a potential role in cell proliferation.
PMID- 28488758
TI - Engineered Humicola insolens cutinase for efficient cellulose acetate
deacetylation.
AB - Cutinases comprise a family of esterases with broad hydrolytic activity for chain
and pendant ester groups. This work aimed to identify and improve an efficient
cutinase for cellulose acetate (CA) deacetylation. The development of a mild
method for CA fiber surface deacetylation will result in improved surface
hydrophilicity and reactivity while, when combined with cellulases, a route to
the full recycling of CA to acetate and glucose. In this study, the comparative
CA deacetylation activity of four homologous wild-type (wt) fungal cutinases from
Aspergillus oryzae (AoC), Thiellavia terrestris (TtC), Fusarium solani (FsC), and
Humicola insolens (HiC) was determined by analysis of CA deacetylation kinetics.
wt-HiC had the highest catalytic efficiency (~32 [cm2 L-1 ]-1 h-1 ). Comparison
of wt-cutinase catalytic constants revealed that differences in catalytic
efficiency are primarily due to corresponding variations in corresponding
substrate binding constants. Docking studies with model tetrameric substrates
also revealed structural origins for differential substrate binding amongst these
cutinases. Comparative docking studies of HiC point mutations led to the
identification of two important rationales for engineering cutinases for CA
deacetylation: (i) create a tight but not too closed binding groove, (ii) allow
for hydrogen bonding in the extended region around the active site. Rationally
designed HiC with amino acid substitutions I36S, predicted to hydrogen bond to
CA, combined with F70A, predicted to remove steric constraints, showed a two-fold
improvement in catalytic efficiency. Continued cutinase optimization guided by a
detailed understanding of structure-activity relationships, as demonstrated here,
will be an important tool to developing practical cutinases for commercial green
chemistry technologies.
PMID- 28488759
TI - Association between T102C 5-HT2A receptor gene polymorphism and 5-year mortality
risk among Brazilian Amazon riparian elderly population.
AB - OBJECTIVE: Serotonin (5-HT) is a pleiotropic molecule that exerts several
functions on brain and peripheral tissues via different receptors. The gene for
the 5-HT2A receptor shows some variations, including a T102C polymorphism, that
have been associated with increased risk of neuropsychiatric and vascular
disorders. However, the potential impact of 5-HT2A imbalance caused by genetic
variations on the human lifespan has not yet been established. METHODS: We
performed a prospective study involving an Amazon riparian elderly free-living
population in Maues City, Brazil, with a 5-year follow-up. Out of a cohort of 637
subjects selected in July, 2009, we genotyped 471 individuals, including 209
males (44.4%) and 262 females (55.6%), all averaging 72.3 +/- 7.8 years of age
(ranging from 60 to 100 years). RESULTS: The T102C-SNP genotypic frequencies were
14.0% TT, 28.0% CC, and 58.0% CT. From 80 elderly individuals who died during the
period investigated, we observed significantly (P = .005) higher numbers of TT
carriers (27.3%) and CC carriers (21.2%), compared to heterozygous CT carriers
(12.5%). Cox-regression analysis showed that association between the T102C-SNP
and elderly survival was independent of age, sex, and other health variables.
CONCLUSIONS: Our findings strongly suggest that imbalance in 5-HT2A may cause
significant disturbances that lead to an increased susceptibility to death for
individuals who are over 60 years of age.
PMID- 28488760
TI - Dysregulated Metabolism of the Amyloid-beta Protein and Therapeutic Approaches in
Alzheimer Disease.
AB - Amyloid-beta protein (Abeta) is the main component of senile plaques in the
brains of Alzheimer disease (AD) patients. Abeta is proteolytically derived from
amyloid-beta precursor protein by beta- and gamma-secretases. Secreted Abeta is
then eliminated from the central nervous system by multiple clearance mechanisms,
including phagocytosis, immune responses, and proteolytic degradation. These
dynamic metabolic processes, which are referred to as Abeta economy, regulate
steady-state brain Abeta levels. Familial AD-linked genetic mutations augment the
production and aggregation of Abeta. In contrast, rare genetic variants that
reduce Abeta production were protective against AD. Moreover, decreased Abeta
clearance has been demonstrated in sporadic AD patients, suggesting that
dysregulation of Abeta economy contributes to the development of AD. Thus,
several approaches to inhibit the production as well as to enhance the clearance
of Abeta have been investigated as potential therapeutics against AD. In this
manuscript, we introduce the molecules and cellular mechanisms involved in the
regulation of Abeta economy and discuss the current understanding of these
processes in the development of therapeutics against AD. J. Cell. Biochem. 118:
4183-4190, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28488761
TI - Apoptotic sperm biomarkers and the correlation between conventional sperm
parameters and clinical characteristics.
AB - The principal aim of this retrospective study was to examine the relationship
between sperm apoptotic biomarkers and the patient's biclinical characteristics,
the conventional sperm parameters and the results of assisted reproductive
technology. Sperm analysis, activated caspases, annexin V staining for
phosphatidylserine (PS) externalisation and labelling assay for DNA fragmentation
were assessed in 122 males of infertile couples. Fifty-seven couples were
allocated to the natural conception group, and 65 couples underwent IVF or ICSI.
Semen of IVF/ICSI patients showed a higher proportion of apoptotic spermatozoa in
their spermatozoa when compared with a natural conception group (p < .05). Sperm
apoptotic biomarkers correlated with age, FSH, and conventional sperm parameters.
DNA fragmentation correlated positively with the percentage of semen having
externalised PS (r = .78, p = 0) and activated caspases (r = .71, p = 0).
Patients without clinical pregnancy had higher frequency of DNA fragmentation,
externalised PS and activated caspases compared to patients with clinical
pregnancy (p < .001). The best specificity and greater sensitivity were obtained
with the test of the DNA fragmentation compared to the other biomarkers. Among
the apoptotic biomarkers, only DNA fragmentation was found to predict natural or
assisted pregnancy better than conventional sperm parameters.
PMID- 28488762
TI - Visual Auras in Epilepsy and Migraine - An Analysis of Clinical Characteristics.
AB - OBJECTIVE: To evaluate the characteristics of visual auras (VA) in epilepsy and
migraine. BACKGROUND: Both disorders are usually diagnosed on clinical grounds,
but differentiation might be challenging in isolated auras or because of the
similar presentation in migraine and epilepsy. METHODS: A retrospective study of
two cohorts was performed to compare the VA characteristics of 27 epilepsy
patients and 27 age-matched migraine patients. RESULTS: The duration of VA was
significantly shorter in epilepsy (median: 56s; 1st quartile Q1: 26s; 3rd
quartile Q3: 130s) than in migraine (20 min; Q1: 10 min; Q3: 30 min) (P < .0001).
A cutoff duration of >=5 minutes identified all migraine patients (100%
sensitivity, 92% specificity). VAs of epileptic etiology were characterized by
restriction to a visual hemifield (74.1% vs 29.6% in migraine, P = .0024) with
stereotypic affection of one hemifield (55.5% vs 7.4% in migraine, P = 0.0003).
Centrifugal or centripetal spread of visual phenomena only occurred in migraine
(37.0%), but not in epilepsy (P = 0.0007). If present, accompanying symptoms such
as nausea/vomiting (19/27) or photo-/phonophobia (17/27) identify migrainous
auras (vs 0/27 in the epilepsy patients; P < .0001). Headache presented in all
migraine patients, but was also observed in six of the epilepsy patients during
cephalic auras or the postictal phase (P < .0001). None of the visual migrainous
auras evolved into an epileptic seizure, a concept called migralepsy.
CONCLUSIONS: Several clinical characteristics differentiate VA of epileptic and
migrainous origin - if presenting in classical manner. Additional EEG evaluations
should be performed in patients with VA of unclear etiology and epileptic VA
features added to current classifications to increase their discriminatory power.
PMID- 28488763
TI - Recent Progress in the Design of Advanced Cathode Materials and Battery Models
for High-Performance Lithium-X (X = O2 , S, Se, Te, I2 , Br2 ) Batteries.
AB - Recent advances and achievements in emerging Li-X (X = O2 , S, Se, Te, I2 , Br2 )
batteries with promising cathode materials open up new opportunities for the
development of high-performance lithium-ion battery alternatives. In this review,
we focus on an overview of recent important progress in the design of advanced
cathode materials and battery models for developing high-performance Li-X (X = O2
, S, Se, Te, I2 , Br2 ) batteries. We start with a brief introduction to explain
why Li-X batteries are important for future renewable energy devices. Then, we
summarize the existing drawbacks, major progress and emerging challenges in the
development of cathode materials for Li-O2 (S) batteries. In terms of the
emerging Li-X (Se, Te, I2 , Br2 ) batteries, we systematically summarize their
advantages/disadvantages and recent progress. Specifically, we review the
electrochemical performance of Li-Se (Te) batteries using carbonate-/ether-based
electrolytes, made with different electrode fabrication techniques, and of Li-I2
(Br2 ) batteries with various cell designs (e.g., dual electrolyte, all-organic
electrolyte, with/without cathode-flow mode, and fuel cell/solar cell
integration). Finally, the perspective on and challenges for the development of
cathode materials for the promising Li-X (X = O2 , S, Se, Te, I2 , Br2 )
batteries is presented.
PMID- 28488764
TI - Astrocytes contribute to Abeta-induced blood-brain barrier damage through
activation of endothelial MMP9.
AB - The blood-brain barrier (BBB) plays an important role in the maintenance of the
brain homeostasis, and its proper functions are warranted by the interplay
between different cellular components (endothelial cells, astrocytes and
pericytes). BBB dysfunctions in pathological conditions, and particularly in
Alzheimer's disease, have been documented. Here, using an in vitroBBB model, the
interaction between endothelial cells and astrocytes exposed to Abeta1-42 was
investigated. Human endothelial cells, cultured in monolayer or co-cultured with
astrocytes, were exposed to Abeta1-42 (2 MUM for 18 h). Abeta induced dysfunction
of endothelial barrier, as assessed by enhanced permeability to FITC-conjugated
dextran and reduced expression of claudin-5; these modifications were observed in
the co-culture model, but not in endothelial cells cultured in monolayer.
Similarly, Abeta-induced damage at the barrier was observed when endothelial
cells were challenged in the presence of conditioned medium generated by
astrocytes previously exposed to Abeta (ACM Abeta). Endothelial barrier damages
were associated with enhanced matrix metalloprotease 9 (MMP9) activity, known to
mediate claudin-5 disruption. These events were not related to the direct effects
played by Abeta on endothelial cells, but they were rather the consequence of
Abeta-induced vascular endothelial growth factor (VEGF) expression in astrocytes.
Indeed, when vascular endothelial growth factor expression was down-regulated in
astrocytes, neither barrier properties or MMP9 expression in endothelial cells
were affected after Abeta exposure both in the co-culture model or in the
presence of ACM Abeta. These data point out the importance of astrocytes'
mediation in inducing endothelial sensitivity to Abeta1-42.
PMID- 28488765
TI - Antitumoral potential, antioxidant activity and carotenoid content of two
Southern Italy tomato cultivars extracts: San Marzano and Corbarino.
AB - Gastric cancer represents a diffuse and aggressive neoplasm, whose mortality
index is among the highest in the world. Predisposing factors are E-cadherin
mutations, Helicobacter pylori infection, and a diet rich in salted and smoked
food, with a low intake of fresh fruits and vegetables. Here, we analyzed the
effect of total lipophilic extracts of two Southern Italy tomato varieties, San
Marzano and Corbarino, on an in vitro model of gastric cancer, YCC-1, YCC-2 and
YCC-3 cell lines, characterized by different aggressiveness. Our results showed a
possible role of these two varieties of tomatoes against typical neoplastic
features. The treatment with tomato extracts affected cancer cell ability to grow
both in adherence and in semisolid medium, reducing also cell migration ability.
No toxic effects were observed on non-tumoral cells. We found, on gastric cancer
cell lines, effects on both cell cycle progression and apoptosis modulation. The
extent of antineoplastic effects, however, did not seem to correlate with the
carotenoid content and antioxidant activity of the two tomato varieties. Our data
indicate that San Marzano and Corbarino intake might be further considered as
nutritional support not only in cancer prevention, but also for cancer patient
diet.
PMID- 28488766
TI - Brief isoflurane anesthesia regulates striatal AKT-GSK3beta signaling and
ameliorates motor deficits in a rat model of early-stage Parkinson's disease.
AB - Parkinson's disease (PD) is a progressive neurodegenerative movement disorder
primarily affecting the nigrostriatal dopaminergic system. The link between
heightened activity of glycogen synthase kinase 3beta (GSK3beta) and neurodegene
rative processes has encouraged investigation into the potential disease
modifying effects of novel GSK3beta inhibitors in experimental models of PD.
Therefore, the intriguing ability of several anesthetics to readily inhibit
GSK3beta within the cortex and hippocampus led us to investigate the effects of
brief isoflurane anesthesia on striatal GSK3beta signaling in naive rats and in a
rat model of early-stage PD. Deep but brief (20-min) isoflurane anesthesia
exposure increased the phosphorylation of GSK3beta at the inhibitory Ser9
residue, and induced phosphorylation of AKTThr308 (protein kinase B; negative
regulator of GSK3beta) in the striatum of naive rats and rats with unilateral
striatal 6-hydroxydopamine (6-OHDA) lesion. The 6-OHDA protocol produced gradual
functional deficiency within the nigrostriatal pathway, reflected as a preference
for using the limb ipsilateral to the lesioned striatum at 2 weeks post 6-OHDA.
Interestingly, such motor impairment was not observed in animals exposed to four
consecutive isoflurane treatments (20-min anesthesia every 48 h; treatments
started 7 days after 6-OHDA delivery). However, isoflurane had no effect on
striatal or nigral tyrosine hydroxylase (a marker of dopaminergic neurons)
protein levels. This brief report provides promising results regarding the
therapeutic potential and neurobiological mechanisms of anesthetics in
experimental models of PD and guides development of novel disease-modifying
therapies.
PMID- 28488767
TI - An assessment of postcranial indices, ratios, and body mass versus eco
geographical variables of prehistoric Jomon, Yayoi agriculturalists, and Kumejima
Islanders of Japan.
AB - OBJECTIVES: We explore variations in body and limb proportions of the Jomon
hunter-gatherers (14,000-2500 BP), the Yayoi agriculturalists (2500-1700 BP) of
Japan, and the Kumejima Islanders of the Ryukyus (1600-1800 AD) with 11
geographically diverse skeletal postcranial samples from Africa, Europe, Asia,
Australia, and North America using brachial-crural indices, femur head-breadth-to
femur length ratio, femur head-breadth-to-lower-limb-length ratio, and body mass
as indicators of phenotypic climatic adaptation. Specifically, we test the
hypothesis that variation in limb proportions seen in Jomon, Yayoi, and Kumejima
is a complex interaction of genetic adaptation; development and allometric
constraints; selection, gene flow and genetic drift with changing cultural
factors (i.e., nutrition) and climate. METHODS: The skeletal data (1127
individuals) were subjected to principle components analysis, Manly's permutation
multiple regression tests, and Relethford-Blangero analysis. RESULTS: The results
of Manly's tests indicate that body proportions and body mass are significantly
correlated with latitude, and minimum and maximum temperatures while limb
proportions were not significantly correlated with these climatic variables.
Principal components plots separated "climatic zones:" tropical, temperate, and
arctic populations. The indigenous Jomon showed cold-adapted body proportions and
warm-adapted limb proportions. Kumejima showed cold-adapted body proportions and
limbs. The Yayoi adhered to the Allen-Bergmann expectation of cold-adapted body
and limb proportions. Relethford-Blangero analysis showed that Kumejima
experienced gene flow indicated by high observed variances while Jomon
experienced genetic drift indicated by low observed variances. CONCLUSIONS: The
complex interaction of evolutionary forces and development/nutritional
constraints are implicated in the mismatch of limb and body proportions.
PMID- 28488768
TI - Mild mitochondrial uncoupling induces HSL/ATGL-independent lipolysis relying on a
form of autophagy in 3T3-L1 adipocytes.
AB - Obesity is characterized by an excessive triacylglycerol accumulation in white
adipocytes. Various mechanisms allowing the tight regulation of triacylglycerol
storage and mobilization by lipid droplet-associated proteins as well as
lipolytic enzymes have been identified. Increasing energy expenditure by inducing
a mild uncoupling of mitochondria in adipocytes might represent a putative
interesting anti-obesity strategy as it reduces the adipose tissue
triacylglycerol content (limiting alterations caused by cell hypertrophy) by
stimulating lipolysis through yet unknown mechanisms, limiting the adverse
effects of adipocyte hypertrophy. Herein, the molecular mechanisms involved in
lipolysis induced by a mild uncoupling of mitochondria in white 3T3-L1 adipocytes
were characterized. Mitochondrial uncoupling-induced lipolysis was found to be
independent from canonical pathways that involve lipolytic enzymes such as HSL
and ATGL. Finally, enhanced lipolysis in response to mitochondrial uncoupling
relies on a form of autophagy as lipid droplets are captured by endolysosomal
vesicles. This new mechanism of triacylglycerol breakdown in adipocytes exposed
to mild uncoupling provides new insights on the biology of adipocytes dealing
with mitochondria forced to dissipate energy.
PMID- 28488769
TI - Selective expression of long non-coding RNAs in a breast cancer cell progression
model.
AB - Long non-coding RNAs (lncRNAs) are acknowledged as regulators of cancer biology
and pathology. Our goal was to perform a stringent profiling of breast cancer
cell lines that represent disease progression. We used the MCF-10 series, which
includes the normal-like MCF-10A, HRAS-transformed MCF-10AT1 (pre-malignant), and
MCF-10CA1a (malignant) cells, to perform transcriptome wide sequencing. From
these data, we have identified 346 lncRNAs with dysregulated expression across
the progression series. By comparing lncRNAs from these datasets to those from an
additional set of cell lines that represent different disease stages and
subtypes, MCF-7 (early stage, luminal), and MDA-MB-231 (late stage, basal), 61
lncRNAs that are associated with breast cancer progression were identified.
Querying breast cancer patient data from The Cancer Genome Atlas, we selected a
lncRNA, IGF-like family member 2 antisense RNA 1 (IGFL2-AS1), of potential
clinical relevance for functional characterization. Among the 61 lncRNAs, IGFL2
AS1 was the most significantly decreased. Our results indicate that this lncRNA
plays a role in downregulating its nearest neighbor, IGFL1, and affects migration
of breast cancer cells. Furthermore, the lncRNAs we identified provide a valuable
resource to mechanistically and clinically understand the contribution of lncRNAs
in breast cancer progression.
PMID- 28488770
TI - Allopurinol for the Treatment of Refractory Aggression: A Case Series.
AB - OBJECTIVE: Allopurinol is a drug indicated for the treatment and prevention of
gout. Through various theorized mechanisms, there has been an observed benefit in
reducing aggression in patients with dementia who are refractory to traditional
interventions. This case series of eight patients reports the use of allopurinol
to treat aggression at the Battle Creek Veterans Affairs Medical Center. METHODS:
Charts of research participants were accessed retrospectively to obtain data.
Adverse event notes were evaluated to identify the number of aggressive events
before the initiation of allopurinol compared with the total number and rates of
aggressive events after the initiation of allopurinol. RESULTS: A total of eight
patients were included in the case series. Of those started on allopurinol for
treating aggression, two showed no effect while all other participants responded
with a decrease in the number and rate of reported aggressive episodes.
CONCLUSIONS: Allopurinol was observed to decrease the number and rate of
aggressive events in patients refractory to other treatments.
PMID- 28488771
TI - Fluorinated surfaces: smart substrates for matrix-free laser desorption
ionization.
PMID- 28488772
TI - Active application of primer acid on acid-treated enamel: Influence on the bond
effectiveness of self-etch adhesives systems.
AB - AIM: Evaluate the composite-to-enamel bond after passive or active application of
self-etching primer systems on polished or pre-etched enamel with phosphoric
acid. MATERIALS AND METHODS: Two self-etch adhesives systems (SEAS) were used:
Clearfil SE Bond and Easy Bond. Third human molars were divided into 8 groups (N
= 10). The crown of each tooth was sectioned into halves and the mesial/distal
surfaces were used. The adhesives were actively or passively applied on enamel
with or without prior phosphoric-acid etching. Resin composite cylinders were
built after adhesive application. After stored in relative humidity for 24 hr/37
degrees C the specimens were subjected to microshear test in universal testing a
machine at a crosshead speed of 0.5 mm/minute. The results were analyzed with
three-way ANOVA and the Tukey test. The enamel-etching pattern was evaluated
under SEM. RESULTS: The 2-step SEAS system presented significantly higher
adhesive bond strength means (47.37 MPa) than the 1-step (36.87 MPa). A poor
enamel- etching pattern was observed in active mode showing irregular and short
resin tags, however there was not compromised the bond strength. CONCLUSION:
Active or passive application produced similar values of bond strength to enamel
regardless of enamel pretreatment and type of SEAS.
PMID- 28488773
TI - Large Modulation of Charge Carrier Mobility in Doped Nanoporous Organic
Transistors.
AB - Molecular doping of organic electronics has shown promise to sensitively modulate
important device metrics. One critical challenge is the disruption of structure
order upon doping of highly crystalline organic semiconductors, which
significantly reduces the charge carrier mobility. This paper demonstrates a new
method to achieve large modulation of charge carrier mobility via channel doping
without disrupting the molecular ordering. Central to the method is the
introduction of nanopores into the organic semiconductor thin films via a simple
and robust templated meniscus-guided coating method. Using this method, the
charge carrier mobility of C8 -benzothieno[3,2-b]benzothiophene transistors is
boosted by almost sevenfold. This paper further demonstrates enhanced electron
transport by close to an order of magnitude in a diketopyrrolopyrrole-based donor
acceptor polymer. Combining spectroscopic measurements, density functional theory
calculations, and electrical characterizations, the doping mechanism is
identified as partial-charge-transfer induced trap filling. The nanopores serve
to enhance the dopant/organic semiconductor charge transfer reaction by exposing
the pi-electrons to the pore wall.
PMID- 28488774
TI - FSCN1 is upregulated by SNAI2 and promotes epithelial to mesenchymal transition
in head and neck squamous cell carcinoma.
AB - In this study, we investigated whether there is any association between the
expression of FSCN1 and SNAI2 and the possible underlying mechanisms in head and
neck squamous cell carcinoma (HNSC). In addition, we also investigated whether
FSCN1 modulates epithelial-to-mesenchymal transition (EMT) in HNSC cells.
Microarray data of dysregulated genes in HNSC were searched in GEO datasets. The
association between FSCN1 expression and the 5-year/10-year overall survival
(OS), as well as the correlation between the expression of FSCN1 and SOX2, MYBL2,
SNAI2, STAT1, and SOX4, was analyzed based on data in TCGA HNSC cohort (TCGA
HNSC). The binding site of SNAI2 in FSCN1 promoter was verified using luciferase
reporter assay. SCC9 and SCC15 cells were transfected with pCMV-SNAI2 or pCMV
FSCN1 expression vector or the empty control. Alteration of E-cadherin, Claudin
1, Vimentin, and N-cadherin was then quantified. Our results showed that FSCN1 is
significantly upregulated in HNSC tissues compared with the normal control
tissues. High FSCN1 expression is associated with worse 5-year and 10-year OS
among the HNSC patients. Bioinformatic prediction showed a highly possible SNAI2
binding site in FSCN1 promoter and following luciferase reporter assay verified
this site. SNAI2 overexpression significantly increased FSCN1 expression at both
mRNA and protein level. FSCN1 overexpression reduced the expression of E-cadherin
and Claudin 1, but increased the expression of Vimentin and N-cadherin in SCC9
and SCC-15 cells. Therefore, we infer that FSCN1 is a downstream effector of
SNAI2 in promoting EMT in HNSC cells.
PMID- 28488775
TI - Effects of Sorbic Acid-Chitosan Microcapsules as Antimicrobial Agent on the
Properties of Ethylene Vinyl Alcohol Copolymer Film for Food Packaging.
AB - This paper discusses the possibility of using sorbic acid-chitosan microcapsules
(S-MPs) as an antibacterial component of active ethylene vinyl alcohol copolymer
(EVOH) film. S-MPs with a diameter of approximately 1 to 4 MUm showed a sorbic
acid loading capacity of 46.5%. Addition of S-MPs (3%, w/w) increased the tensile
strength, haze, oxygen, and water vapor barrier properties, as well as reduced
the elongations at break and transmittance of S-MPs-EVOH (S-MP-EVOH) film.
Antibacterial tests showed that the inhibitory capacity of S-MP-EVOH film against
Salmonella Enteritidis and Escherichia coli was higher than that against Listeria
monocytogenes. Moreover, the antibacterial effect of sorbic acid-EVOH (S-EVOH)
film was stronger than that of S-MP-EVOH film. However, S-MP-EVOH film
demonstrated a longer effective time than S-EVOH film. Using the total viable
counts and total volatile base nitrogen as the judgment standard, S-MP
EVOH/polyethylene terephthalate (PET) composite film could extend the shelf life
of fish fillets by 4 d at 4 degrees C, compared with EVOH/PET film. For this
reason, S-MP could be a potential antibacterial component of active films.
PMID- 28488776
TI - Optochemically Responsive 2D Nanosheets of a 3D Metal-Organic Framework Material.
AB - Outstanding functional tunability underpinning metal-organic framework (MOF)
confers a versatile platform to contrive next-generation chemical sensors,
optoelectronics, energy harvesters, and converters. A rare exemplar of a porous
2D nanosheet material constructed from an extended 3D MOF structure is reported.
A rapid supramolecular self-assembly methodology at ambient conditions to
synthesize readily exfoliatable MOF nanosheets, functionalized in situ by
adopting the guest@MOF (host) strategy, is developed. Nanoscale confinement of
light-emitting molecules (as functional guest) inside the MOF pores generates
unusual combination of optical, electronic, and chemical properties, arising from
the strong host-guest coupling effects. Highly promising photonics-based chemical
sensing opened up by the new guest@MOF composite systems is shown. By harnessing
host-guest optochemical interactions of functionalized MOF nanosheets, detection
of an extensive range of volatile organic compounds and small molecules important
for many practical applications has been accomplished.
PMID- 28488777
TI - MicroRNA-224-5p regulates adipocyte apoptosis induced by TNFalpha via controlling
NF-kappaB activation.
AB - Tumor necrosis factor (TNF) alpha can induce cell apoptosis and activate nuclear
transcription (NF)-kappaB in different cell types. Activated NF-kappaB further
promotes or suppresses cellular apoptosis in different cases. The present study
explored the effect of activated NF-kappaB on adipocyte apoptosis induced by
TNFalpha and which microRNAs (miRNAs) were involved in the process. Our findings
demonstrated that treatment of differentiated 3T3-L1 adipocytes with TNFalpha (20
ng/mL) rapidly activated NF-kappaB and induced moderate apoptosis.
Pyrrolidinedithiocarbamic acid (PDTC, 60 uM), a specific NF-kappaB inhibitor,
abated NF-kappaB activation that rendered the adipocytes vulnerable to TNFalpha
induced apoptosis. Dozens of miRNAs exhibited significant expression changes
following TNFalpha treatment and the addition of PDTC. In which, miRNA-224-5p
(miR-224) was up-regulated by TNFalpha exposure but down-regulated by PDTC
addition. Furthermore, over-expression of miR-224 promoted NF-kappaB activation
and prevented the adipocyte apoptosis induced by TNFalpha, while miR-224
deficiency showed the opposite effects. The TRAF-associated NF-kappaB activator
(TANK) gene was identified as a direct target of miR-224 by computational and
luciferase reporter assays. Additionally, silencing the TANK gene by the small
interfering RNA similarly promoted NF-kappaB activation and attenuated the
cellular apoptosis. In conclusion, these findings demonstrate that miR-224 plays
an essential role in adipocyte apoptosis caused by TNFalpha through control of NF
kappaB activation via targeting the TANK gene.
PMID- 28488778
TI - Total Syntheses of Lepadiformine Marine Alkaloids with Enantiodivergency,
Utilizing Hg(OTf)2 -Catalyzed Cycloisomerization Reaction and their Cytotoxic
Activities.
AB - The enantioselective total syntheses of lepadiformine marine alkaloids,
azatricyclic natural products isolated from marine tunicates, were completed.
These alkaloids have a unique chemical structure characterized by the trans-1
azadecalin (AB ring system) fused with the spirocyclic ring (AC ring system).
Here we found that a cycloisomerization reaction from functionalized linear
substrates to a 1-azaspiro[4.5]decane framework corresponding to the AC ring in
lepadiformines is promoted by a catalytic amount of mercury(II) triflate
(Hg(OTf)2 ). The total syntheses of (-)-lepadiformines A and B were achieved in
28 % and 21 % overall yields, respectively, through the novel cycloisomerization
reaction. The syntheses of (+)- and (-)-lepadiformine C hydrochloride salts also
enabled us to determine the absolute configuration of natural lepadiformine C. It
has been found that a phenomenon of enantiodivergence occurs in lepadiformine
alkaloids from a single species of marine tunicate, Clavelina moluccensis. The
cytotoxic activities of synthesized lepadiformine hydrochloride salts and their
synthetic intermediates were evaluated.
PMID- 28488779
TI - Nociceptor plasticity: A closer look.
AB - Nociceptors are receptors specifically involved in detecting a tissue damage and
transducing it in an electrical signal. Nociceptor activation provoked by any
kind of acute lesion is related to the release of several mediators of
inflammation, within the framework of a process defined as "peripheral
sensitization." This results in an exaggerated response to the painful stimulus,
clinically defined as "primary hyperalgesia." The concept of "neuroplasticity"
may explain the adaptive mechanisms carried out by the Nervous System in relation
to a "harmful" damage; also, neuroplasticity mechanisms are also fundamental for
rehabilitative intervention protocols. Here we review several studies that
addressed the role of different receptors and ionic channels discovered on
nociceptor surface and their role in pain perception. The changes in expression,
distribution, and functioning of receptors and ionic channels are thought to be a
part of the neuroplasticity property, through which the Nervous System constantly
adapts to external stimuli. Moreover, some of the reviewed mediators are also
been associated to "central sensitization," a process that results in pain
chronicization when the painful stimulation is particularly prolonged or intense,
and lastly leads to the memorization of the uncomfortable painful perception.
PMID- 28488780
TI - Electrostatic Design of 3D Covalent Organic Networks.
AB - An innovative strategy for electrostatically designing the electronic structure
of 3D bulk materials is proposed to control charge carriers at the nanoscale.
This is achieved by shifting the electronic levels of chemically identical
semiconducting elements through the periodic arrangement of polar functional
groups. For the example of covalent organic networks, by first-principles
calculations, the resulting collective electrostatic effects are shown to allow a
targeted manipulation of the electronic landscape such that spatially confined
pathways for electrons and holes can be realized. Mimicking donor-acceptor bulk
heterojunctions, the new materials hold high promise for photovoltaic
applications. The distinct advantage over the conventional approach of splitting
excitons through chemically distinct donor and acceptor units is that here the
magnitude of the band offset can be continuously tuned by varying the dipole
density. A particularly promising feature of the suggested strategy is its
structural versatility, which also enables the realization of more complex
quantum structures such as quantum-cascades and quantum-checkerboards.
PMID- 28488781
TI - Deciphering the effects of disperser assemblages and seed mass on patterns of
seed dispersal in a rodent community.
AB - The sizes of both seed dispersers and seeds are traits that are likely to
interact to influence seed fate in many synzoochoric plant species. Here, we
examined whether members of a granivorous rodent community consisting of species
of different body size vary in their effectiveness as seed dispersers, and how
this relationship may be altered by seed size. We marked northern red oak
(Quercus rubra) acorns with plastic tags and placed them in size-selective rodent
exclosures. The exclosures allowed differential access of rodent groups based on
different body size: (i) small (e.g. Peromyscus spp.); (ii) small and medium
(e.g. Tamias striatus); and (iii) small, medium and large (e.g. Sciurus
carolinensis) species of rodents. Acorn removal did not differ among exclosure
types, but more seeds were missing when removed by small rodents, probably
because of larderhoarding. The treatments did not influence the relative
frequency of acorn consumption. However, small rodents cached considerably fewer
and partially ate more acorns than the other 2 groups. The mean dispersal
distance was the longest for cages with medium openings, intermediate for cages
with large openings and the shortest for cages with small openings. Acorn mass
positively affected the probability of caching and this relationship was
unaffected by exclosure type. In conclusion, granivorous rodents of different
body sizes strongly differed in their interactions with acorns, with small
rodents acting primarily as acorn predators and medium and large species
contributing significantly more to dispersal of red oaks.
PMID- 28488782
TI - Survivorship care plans in Spain: A need that cannot be postponed.
AB - In Spain, as around the world, the number of cancer survivors is increasing.
There were an estimated 500,000 cancer survivors in 2010. In spite of recognition
that Survivorship Care Plans (SCPs) are needed, their implementation in Spain has
been slower than in other countries and only in very recent years some small
initiatives have been carried out. This editorial addresses the difficulties to
implement SCPs in the Spanish Health Services and which are the opportunities
that favour a scenario in which PCPs and oncologists can offer a real patient
centred care to cancer survivors.
PMID- 28488783
TI - Light adaptation and the evolution of vertebrate photoreceptors.
AB - KEY POINTS: Lamprey are cyclostomes, a group of vertebrates that diverged from
lines leading to jawed vertebrates (including mammals) in the late Cambrian, 500
million years ago. It may therefore be possible to infer properties of
photoreceptors in early vertebrate progenitors by comparing lamprey to other
vertebrates. We show that lamprey rods and cones respond to light much like rods
and cones in amphibians and mammals. They operate over a similar range of light
intensities and adapt to backgrounds and bleaches nearly identically. These
correspondences are pervasive and detailed; they argue for the presence of rods
and cones very early in the evolution of vertebrates with properties much like
those of rods and cones in existing vertebrate species. ABSTRACT: The earliest
vertebrates were agnathans - fish-like organisms without jaws, which first
appeared near the end of the Cambrian radiation. One group of agnathans became
cyclostomes, which include lamprey and hagfish. Other agnathans gave rise to
jawed vertebrates or gnathostomes, the group including all other existing
vertebrate species. Because cyclostomes diverged from other vertebrates 500
million years ago, it may be possible to infer some of the properties of the
retina of early vertebrate progenitors by comparing lamprey to other vertebrates.
We have previously shown that rods and cones in lamprey respond to light much
like photoreceptors in other vertebrates and have a similar sensitivity. We now
show that these affinities are even closer. Both rods and cones adapt to
background light and to bleaches in a manner almost identical to other vertebrate
photoreceptors. The operating range in darkness is nearly the same in lamprey and
in amphibian or mammalian rods and cones; moreover background light shifts
response-intensity curves downward and to the right over a similar range of
ambient intensities. Rods show increment saturation at about the same intensity
as mammalian rods, and cones never saturate. Bleaches decrease sensitivity in
part by loss of quantum catch and in part by opsin activation of transduction.
These correspondences are so numerous and pervasive that they are unlikely to
result from convergent evolution but argue instead that early vertebrate
progenitors of both cyclostomes and mammals had photoreceptors much like our own.
PMID- 28488784
TI - CT-determined pulmonary artery to aorta ratio as a predictor of elevated
pulmonary artery pressure and survival in idiopathic pulmonary fibrosis.
AB - BACKGROUND AND OBJECTIVE: Elevated mean pulmonary artery pressure (mPAP) is a
significant prognostic indicator in idiopathic pulmonary fibrosis (IPF). It has
been reported that the computed tomography-determined ratio of the diameter of
the pulmonary artery to the aorta (PA:A) is correlated with mPAP in various
respiratory diseases. However, in patients with IPF, whether the PA:A can be used
to predict elevated mPAP and the prognostic value of the PA:A has not been fully
evaluated. METHODS: We conducted a single-centre, observational study of 177
consecutive IPF patients who underwent right heart catheterization. We examined
the association between the PA:A and mPAP in these patients, and performed a
receiver operating characteristic (ROC) analysis to test the diagnostic accuracy
of the PA:A in predicting mPAP > 20 mm Hg (pulmonary hypertension (PH) or
borderline PH) in relation to survival. RESULTS: In a multivariate linear
regression analysis, the PA:A, 6-min walk distance and diffusion capacity for
carbon monoxide (DLCO ) % predicted were independent explanatory variables of
elevated mPAP (P < 0.0001, P = 0.009 and P = 0.002, respectively). ROC analysis
revealed a PA:A > 0.9 to be optimal for predicting mPAP > 20 mmHg (area under the
curve (AUC) = 0.75; 95% CI: 0.65-0.84). Patients with a PA:A > 0.9 also had a
worse prognosis (P = 0.009). CONCLUSION: Measurement of the PA:A is a useful and
convenient method to predict elevated mPAP in IPF at initial evaluation.
Moreover, a PA:A >0.9 was found to be an indicator of worse prognosis.
PMID- 28488785
TI - Is it acceptable to use coagulation plasma samples stored at room temperature and
4 degrees C for 24 hours for additional prothrombin time, activated partial
thromboplastin time, fibrinogen, antithrombin, and D-dimer testing?
AB - INTRODUCTION: Coagulation laboratories are faced on daily basis with requests for
additional testing in already analyzed fresh plasma samples. This prompted us to
examine whether plasma samples stored at room temperature (RT), and 4 degrees C
for 24 hours can be accepted for additional prothrombin time (PT), activated
partial thromboplastin time (aPTT), fibrinogen (Fbg), antithrombin (AT), and D
dimer testing. METHODS: We measured PT, aPTT, Fbg in 50 and AT in 30 plasma
samples with normal and pathological values, within 4 hours of blood collection
(baseline results) and after 24-hours storage at RT (primary tubes), and 4
degrees C (aliquots). D-dimer stability was investigated in 20 samples stored in
primary tubes at 4 degrees C. RESULTS: No statistically significant difference
between baseline results and results in samples stored at RT and 4 degrees C was
observed for PT (P=.938), aPTT (P=.186), Fbg (P=.962), AT (P=.713), and D-dimers
(P=.169). The highest median percentage changes were found for aPTT, being more
pronounced for samples stored at 4 degrees C (13.0%) than at RT (8.7%).
CONCLUSION: Plasma samples stored both at RT and 4 degrees C for 24 hours are
acceptable for additional PT, Fbg, and AT testing. Plasma samples stored 24 hours
in primary tubes at 4 degrees C are suitable for D-dimer testing.
PMID- 28488786
TI - Gadoxetic acid-enhanced magnetic resonance imaging reflects co-activation of beta
catenin and hepatocyte nuclear factor 4alpha in hepatocellular carcinoma.
AB - AIM: The aim of this study is to clarify the correlation of the co-activation of
beta-catenin and hepatocyte nuclear factor (HNF)4alpha with the findings of
gadoxetic acid-enhanced magnetic resonance imaging (MRI), organic anion
transporting polypeptide (OATP)1B3 expression, and histological findings in
hepatocellular carcinoma (HCC). METHODS: One hundred and ninety-six HCCs
surgically resected from 174 patients were enrolled in this study. The HCCs were
classified into four groups by immunohistochemical expression of beta-catenin,
glutamine synthetase (GS), and HNF4alpha: (i) beta-catenin/GS (positive [+])
HNF4alpha (+); (ii) beta-catenin/GS (+) HNF4alpha (negative [-]); (iii) beta
catenin/GS (-) HNF4alpha (+); and (iv) beta-catenin/GS (-) HNF4alpha (-). We
compared the four groups in terms of the enhancement ratio on the hepatobiliary
phase of gadoxetic acid-enhanced MRI, immunohistochemical organic anion
transporter polypeptide (OATP)1B3 (a main uptake transporter of gadoxetic acid)
expression and histological features, overall survival, and no recurrence
survival. The Kruskal-Wallis test, Steel-Dwass multiple comparisons test,
Fisher's exact test, and log-rank (Mantel-Cox) test were used for statistical
analyses. RESULTS: Enhancement ratio on gadoxetic acid-enhanced MRI in HCC with
beta-catenin/GS (+) HNF4alpha (+) was significantly higher than those of the
other three groups (P < 0.001). The OATP1B3 grade was also significantly higher
in HCC with beta-catenin/GS (+) HNF4alpha (+) (P < 0.001). Hepatocellular
carcinoma with beta-catenin/GS (+) HNF4alpha (+) showed the highest
differentiation grade as compared to the other groups (P < 0.004). There were no
significant differences in portal vein invasion, macroscopic growth pattern, or
prognosis analyses between the four groups. CONCLUSION: Co-activation of beta
catenin and HNF4alpha would promote OATP1B3 expression, and consequently higher
enhancement ratio on gadoxetic acid-enhanced MRI and higher differentiation grade
in HCC.
PMID- 28488787
TI - Nitrotoga is selected over Nitrospira in newly assembled biofilm communities from
a tap water source community at increased nitrite loading.
AB - Community assembly is a central topic in microbial ecology: how do assembly
processes interact and what is the relative contribution of stochasticity and
determinism? Here, we exposed replicate flow-through biofilm systems, fed with
nitrite-supplemented tap water, to continuous immigration from a source
community, present in the tap water, to determine the extent of selection and
neutral processes in newly assembled biofilm communities at both the community
and the functional guild (of nitrite-oxidizing bacteria, NOB) levels. The
community composition of biofilms assembled under low and high nitrite loading
was described after 40 days of complete nitrite removal. The total community
assembly, as well as the NOB guild assembly were largely governed by a
combination of deterministic and stochastic processes. Furthermore, we observed
deterministic enrichment of certain types of NOB in the biofilms. Specifically,
elevated nitrite loading selected for a single Nitrotoga representative, while
lower nitrite conditions selected for a number of Nitrospira. Therefore, even
when focusing on ecologically coherent ensembles, assembly is the result of
complex stochastic and deterministic processes that can only be interrogated by
observing multiple assemblies under controlled conditions.
PMID- 28488788
TI - Solvent-Free Self-Assembly to the Synthesis of Nitrogen-Doped Ordered Mesoporous
Polymers for Highly Selective Capture and Conversion of CO2.
AB - A solvent-free induced self-assembly technology for the synthesis of nitrogen
doped ordered mesoporous polymers (N-OMPs) is developed, which is realized by
mixing polymer precursors with block copolymer templates, curing at 140-180
degrees C, and calcination to remove the templates. This synthetic strategy
represents a significant advancement in the preparation of functional porous
polymers through a fast and scalable yet environmentally friendly route, since no
solvents or catalysts are used. The synthesized N-OMPs and their derived
catalysts are found to exhibit competitive CO2 capacities (0.67-0.91 mmol g-1 at
25 degrees C and 0.15 bar), extraordinary CO2 /N2 selectivities (98-205 at 25
degrees C), and excellent activities for catalyzing conversion of CO2 into cyclic
carbonate (conversion >95% at 100 degrees C and 1.2 MPa for 1.5 h). The solvent
free technology developed in this work can also be extended to the synthesis of N
OMP/SiO2 nanocomposites, mesoporous SiO2 , crystalline mesoporous TiO2 , and
TiPO, demonstrating its wide applicability in porous material synthesis.
PMID- 28488789
TI - Iron-Catalyzed Intermolecular 1,2-Difunctionalization of Styrenes and Conjugated
Alkenes with Silanes and Nucleophiles.
AB - The first iron-catalyzed 1,2-difunctionalization of styrenes and conjugated
alkenes with silanes and either N or C, using an oxidative radical strategy, is
described. Employing FeCl2 and di-tert-butyl peroxide allows divergent alkene 1,2
difunctionalizations, including 1,2-aminosilylation, 1,2-arylsilylation, and 1,2
alkylsilylation, which rely on a wide range of nucleophiles, namely, amines,
amides, indoles, pyrroles, and 1,3-dicarbonyls, thus providing a powerful
platform for producing diverse silicon-containing alkanes.
PMID- 28488790
TI - Pseudohalide-Exchanged Quantum Dot Solids Achieve Record Quantum Efficiency in
Infrared Photovoltaics.
AB - Application of pseudohalogens in colloidal quantum dot (CQD) solar-cell active
layers increases the solar-cell performance by reducing the trap densities and
implementing thick CQD films. Pseudohalogens are polyatomic analogs of halogens,
whose chemistry allows them to substitute halogen atoms by strong chemical
interactions with the CQD surfaces. The pseudohalide thiocyanate anion is used to
achieve a hybrid surface passivation. A fourfold reduced trap state density than
in a control is observed by using a suite of field-effect transistor studies.
This translates directly into the thickest CQD active layer ever reported,
enabled by enhanced transport lengths in this new class of materials, and leads
to the highest external quantum efficiency, 80% at the excitonic peak, compared
with previous reports of CQD solar cells.
PMID- 28488791
TI - Assessment of semi-quantitative grading of red blood cell abnormalities utilizing
images from the CellaVision DM96 compared to manual light microscopy.
PMID- 28488792
TI - Comprehensive database of Manufactured Gas Plant tars. Part A. Database.
AB - RATIONALE: Coal tars are a mixture of organic and inorganic compounds that were
by-products from the manufactured gas and coke making industries. Different
manufacturing processes have resulted in the production of distinctly different
tar compositions. This study presents a comprehensive database of compounds
produced using two-dimensional gas chromatography combined with time-of-flight
mass spectrometry (GCxGC/TOFMS), analysing 16 tar samples produced by five
distinct production processes. METHODS: Samples of coal tar were extracted using
accelerated solvent extraction (ASE) and derivatised post-extraction using N,O
bis(trimethylsilyl)trifluoroacetamide (BSTFA) with 1% trimethylchlorosilane
(TMCS). The derivatised samples were analysed using two-dimensional gas
chromatography combined with time-of-flight mass spectrometry (GCxGC/TOFMS).
RESULTS: A total of 16 tar samples originating from five different production
processes: Low Temperature Horizontal Retorts, Horizontal Retorts, Vertical
Retorts, Carbureted Water Gas and Coke Ovens, were analysed. A total of 2369
unique compounds were detected with 948 aromatic compounds, 196 aliphatic
compounds, 380 sulfur-containing compounds, 209 oxygen-containing compounds, 262
nitrogen-containing compounds and 15 mixed heterocycles. Derivatisation allowed
the detection of 359 unique compounds, the majority in the form of hydroxylated
polycyclic aromatic hydrocarbons, many of which would not have been detected
without derivatisation. Of the 2369 unique compounds detected, 173 were found to
be present within all samples. CONCLUSIONS: A unique comprehensive database of
compounds detected within 16 tar samples from five different production processes
was produced. The 173 compounds identified within every sample may be of
particular importance from a regulatory standpoint. This initial study indicates
that different production processes produce tars with different chemical
signatures and it can be further expanded upon by in-depth analysis of the
different compound types. The number of compounds presented within this database
clearly demonstrates the analytical power of GCxGC/TOFMS.
PMID- 28488793
TI - Atomic force microscopy studies of bioprocess engineering surfaces - imaging,
interactions and mechanical properties mediating bacterial adhesion.
AB - The detrimental effect of bacterial biofilms on process engineering surfaces is
well documented. Thus, interest in the early stages of bacterial biofilm
formation; in particular bacterial adhesion and the production of anti-fouling
coatings has grown exponentially as a field. During this time, Atomic force
microscopy (AFM) has emerged as a critical tool for the evaluation of bacterial
adhesion. Due to its versatility AFM offers not only insight into the
topographical landscape and mechanical properties of the engineering surfaces,
but elucidates, through direct quantification the topographical and biomechnical
properties of the foulants The aim of this review is to collate the current
research on bacterial adhesion, both theoretical and practical, and outline how
AFM as a technique is uniquely equipped to provide further insight into the
nanoscale world at the bioprocess engineering surface.
PMID- 28488794
TI - Apoptotic Activity of Lactobacillus plantarum DGK-17-Fermented Soybean Seed
Extract in Human Colon Cancer Cells via ROS-JNK Signaling Pathway.
AB - Fermented food has been always possesses upper hand compared to normal food due
to its antibacterial, antioxidant, and anticancer properties. Soybeans, which
have high nutritional value, are widely consumed in Korea. In this study, soybean
seed powder fermented with Lactobacillus plantarum DGK-17, which was previously
isolated from kimchi, showed anticancer potential. Fermented soybean extract
(FSE) resulted in morphological changes, reduction of cancer cell colony
formation and apoptotic cell death of HCT-116 colon cancer cells in a dose
dependent manner, and IC50 value of 111 MUg. FSE treatment caused reduction of
cell growth in a dose-dependent manner via release of lactate dehydrogenase. FSE
treatment induced HCT-116 apoptotic cell death as confirmed by the presence of
fragmented nuclei, oxidative burst, and reduced mitochondrial membrane potential
(DeltaPsim ). Further, FSE treatment sensitized cells to ER stress via IRE1-alpha
induction. FSE treatment also resulted in JNK activation, subsequently causing
activation of Bax and downregulation of BCl2. Weakened mitochondrial membrane
potential (DeltaPsim ) also caused release of Cyto C, further activating caspase
mediated cell death. Therefore, this study reveals the apoptotic role of DGK-17
fermented soybean seed extract in human colon cancer HCT-116 cells.
PMID- 28488795
TI - The novel bacterial phylum Calditrichaeota is diverse, widespread and abundant in
marine sediments and has the capacity to degrade detrital proteins.
AB - Calditrichaeota is a recently recognized bacterial phylum with three cultured
representatives, isolated from hydrothermal vents. Here we expand the phylogeny
and ecology of this novel phylum with metagenome-derived and single-cell genomes
from six uncultivated bacteria previously not recognized as members of
Calditrichaeota. Using 16S rRNA gene sequences from these genomes, we then
identified 322 16S rRNA gene sequences from cultivation-independent studies that
can now be classified as Calditrichaeota for the first time. This dataset was
used to re-analyse a collection of 16S rRNA gene amplicon datasets from marine
sediments showing that the Calditrichaeota are globally distributed in the seabed
at high abundance, making up to 6.7% of the total bacterial community. This wide
distribution and high abundance of Calditrichaeota in cold marine sediment has
gone unrecognized until now. All Calditrichaeota genomes show indications of a
chemoorganoheterotrophic metabolism with the potential to degrade detrital
proteins through the use of extracellular peptidases. Most of the genomes contain
genes encoding proteins that confer O2 tolerance, consistent with the relatively
high abundance of Calditrichaeota in surficial bioturbated part of the seabed
and, together with the genes encoding extracellular peptidases, suggestive of a
general ecophysiological niche for this newly recognized phylum in marine
sediment.
PMID- 28488796
TI - Will the safe-breakers of sleep apnoea find the right combination?
PMID- 28488797
TI - Conformational flexibility in the RNA stem-loop structures formed by CAG repeats.
AB - The expansion of CAG repeats has been found to be associated with at least nine
human genetic disorders. In these disorders, the full-length expanded CAG RNA
transcripts are cleaved into small CAG-repeated RNAs which are cytotoxic and
known to be capable of forming hairpins. To better understand the RNA pathogenic
mechanism, in this study we have performed high-resolution nuclear magnetic
resonance structural investigations on the RNA hairpins formed by CAG repeats.
Our results show the formation of a type III AGCA tetraloop and reveal the effect
of stem rigidity on the loop conformational flexibility.
PMID- 28488798
TI - A comparison of sedimentary DNA and pollen from lake sediments in recording
vegetation composition at the Siberian treeline.
AB - Reliable information on past and present vegetation is important to project
future changes, especially for rapidly transitioning areas such as the boreal
treeline. To study past vegetation, pollen analysis is common, while current
vegetation is usually assessed by field surveys. Application of detailed
sedimentary DNA (sedDNA) records has the potential to enhance our understanding
of vegetation changes, but studies systematically investigating the power of this
proxy are rare to date. This study compares sedDNA metabarcoding and pollen
records from surface sediments of 31 lakes along a north-south gradient of
increasing forest cover in northern Siberia (Taymyr peninsula) with data from
field surveys in the surroundings of the lakes. sedDNA metabarcoding recorded 114
plant taxa, about half of them to species level, while pollen analyses identified
43 taxa, both exceeding the 31 taxa found by vegetation field surveys. Increasing
Larix percentages from north to south were consistently recorded by all three
methods and principal component analyses based on percentage data of vegetation
surveys and DNA sequences separated tundra from forested sites. Comparisons of
the ordinations using procrustes and protest analyses show a significant fit
among all compared pairs of records. Despite similarities of sedDNA and pollen
records, certain idiosyncrasies, such as high percentages of Alnus and Betula in
all pollen and high percentages of Salix in all sedDNA spectra, are observable.
Our results from the tundra to single-tree tundra transition zone show that
sedDNA analyses perform better than pollen in recording site-specific richness
(i.e., presence/absence of taxa in the vicinity of the lake) and perform as well
as pollen in tracing vegetation composition.
PMID- 28488799
TI - Systematic review of exercise training in colorectal cancer patients during
treatment.
AB - Colorectal cancer surgery results in considerable postoperative morbidity,
mortality and reduced quality of life. As many patients will undergo additional
(neo)adjuvant therapy, it is imperative that each individual optimize their
physical function. To elucidate the potential of exercise in patient
optimization, we investigated the evidence for an exercise program before and
after surgical treatment in colorectal cancer patients. A systematic review was
conducted according to the Cochrane Handbook for Systematic Reviews of
Interventions, the guidelines of the Physical Therapy Journal and the PRISMA
guidelines. No literature pertaining to exercise training during preoperative
neoadjuvant treatment was found. Seven studies, investigating the effects of
regular exercise during adjuvant chemotherapy for patients with colorectal cancer
or a mixed population, were identified. A small effect (effect size (ES) 0.4) of
endurance/interval training and strength training (ES 0.4) was found in two
studies conducted in patients with colorectal and gastrointestinal cancer. In
five studies that included a mixed population of cancer patients, interval
training resulted in a large improvement (ES 1.5; P<=.05). Endurance training
alone was found to increase both lower extremity strength and endurance capacity.
The effects of strength training in the lower extremity are moderate, whereas, in
the upper extremity, the increase is small. There is limited evidence available
on exercise training during treatment in colorectal cancer patients. One study
concluded exercise therapy may be beneficial for colorectal cancer patients
during adjuvant treatment. The possible advantages of training during neoadjuvant
treatment may be explored by prehabilitation trials.
PMID- 28488800
TI - Relevance of ethnic differences in factor XIII activity on laboratory reference
ranges.
PMID- 28488801
TI - Measuring and achieving the best possible outcomes in surgery.
PMID- 28488802
TI - Profound spherocytosis in adulthood: Acquired, hereditary or both?
PMID- 28488803
TI - Promises and Challenges in Continuous Tracking Utilizing Amino Acids in Skin
Secretions for Active Multi-Factor Biometric Authentication for Cybersecurity.
AB - We consider a new concept of biometric-based cybersecurity systems for active
authentication by continuous tracking, which utilizes biochemical processing of
metabolites present in skin secretions. Skin secretions contain a large number of
metabolites and small molecules that can be targeted for analysis. Here we argue
that amino acids found in sweat can be exploited for the establishment of an
amino acid profile capable of identifying an individual user of a mobile or
wearable device. Individual and combinations of amino acids processed by
biocatalytic cascades yield physical (optical or electronic) signals, providing a
time-series of several outputs that, in their entirety, should suffice to
authenticate a specific user based on standard statistical criteria. Initial
results, motivated by biometrics, indicate that single amino acid levels can
provide analog signals that vary according to the individual donor, albeit with
limited resolution versus noise. However, some such assays offer digital
separation (into well-defined ranges of values) according to groups such as age,
biological sex, race, and physiological state of the individual. Multi-input
biocatalytic cascades that handle several amino acid signals to yield a single
digital-type output, as well as continuous-tracking time-series data rather than
a single-instance sample, should enable active authentication at the level of an
individual.
PMID- 28488805
TI - Breastfeeding Considerations for Mothers of Infants with Neonatal Abstinence
Syndrome.
AB - Breastfeeding offers many benefits to both mother and baby. Breastfeeding is
generally recommended for mothers of infants with neonatal abstinence syndrome
(NAS) unless some associated risk outweighs the benefits. Evidence indicates that
infants with NAS who receive human milk require less pharmacologic treatment and
have shorter hospital lengths of stay. Perhaps the greatest barrier to
breastfeeding for women with opioid dependence is the inaccurate and inconsistent
information they receive from different sources, including health care
professionals. The American Congress of Obstetricians and Gynecologists, American
Academy of Pediatrics, and Academy of Breastfeeding Medicine (ABM) have published
statements that support breastfeeding infants with NAS. The ABM has a dedicated
protocol to guide clinicians in deciding which mothers should and which mothers
should not breastfeed their infants. In this review, studies evaluating the
effects of breastfeeding, professional organizations' protocols and
recommendations regarding breastfeeding, and barriers to breastfeeding infants
with NAS are discussed, as well as the dangers of illicit drug exposure and
avoiding rebound NAS in a breastfed infant. Clinicians can play an important role
in in identifying, supporting, counseling, and advocating for mothers who wish to
breastfeed their infant with NAS.
PMID- 28488804
TI - Three-Dimensional Shape and Surface Features Distinguish Multiple Sclerosis
Lesions from Nonspecific White Matter Disease.
AB - BACKGROUND AND PURPOSE: There remains a need to further refine the ability of
clinicians to differentiate multiple sclerosis (MS) from other disease
etiologies. Here, we illustrate the value of 3-dimensional (3D) geometric shape
and surface lesion characteristics between disease states. METHODS: Standardized
3-Tesla 3D brain magnetic resonance imaging studies were performed on enrolled MS
and nonspecific white matter (NSWM) patients. Focal supratentorial lesions were
identified, reconstructed using maximum intensity projection, manually segmented,
and 3D printed. Printed 3D models were randomly evaluated by three blinded raters
for selected shape and surface characteristics. Regression models adjusting for
age, disease duration, and individual patient effects were applied to assess
lesion characteristics between patient groups. Patient-level and latent class
analyses between groups were performed. RESULTS: A total of 1,001 supratentorial
lesions were analyzed (710 MS; 291 NSWM) from 30 patients (19 with confirmed MS
[11 female; median age = 33.6 years, range: 26.9-54.5], median disease duration =
2.2 years [.4-19.4]), 11 with verified nonspecific white matter (NSWM) disease
without MS (11 female; median age = 55.0 years, range: 27.9-66.2). Lesions
originating from MS in comparison to NSWM patients demonstrated a higher
percentage of asymmetry (75.9% vs. 43%; OR: 4.39 [2.37-8.12]; P < .001), complex
surface morphologies (65.9% vs. 27.8%; OR: 2.3 [1.74-3.05]; P < .001), and were
multilobular (11.0% vs. .3%, P < .001), and elongated (12.8% vs. 2.4%, P < .001)
in shape. Spatially, these traits were of higher frequency within the
juxtacortical, deep white matter, and periventricular regions. CONCLUSION: Three
dimensional lesion data may provide new biologic insights related to injury along
with offering another approach for determining the origin of lesion types.
PMID- 28488806
TI - Knowledge Management in healthcare libraries: the current picture.
AB - Knowledge management has seen something of a resurgence in attention amongst
health librarians recently. Of course it has never ceased to exist, but now many
library staff are becoming more involved in organisational knowledge management,
and positioning themselves as key players in the sphere. No single model of
knowledge management is proliferating, but approaches that best fit the
organisation's size, structure and culture, and a blending of evidence based
practice and knowledge sharing. Whatever it is called and whatever models are
used, it's clear that for librarians and information professionals, the
importance of putting knowledge and evidence into practice, sharing knowledge
well and capturing it effectively, are still what we will continue to do.
PMID- 28488807
TI - The information needs of occupational therapy students: a case study.
AB - This article summarises a case study on the information needs of Masters level
Occupational Therapy 5 (OT) students at one English university. A mixed methods
questionnaire was used to explore motivators for information-seeking, preferred
information resources and barriers inhibiting the satisfaction of information
needs. Thirteen recommendations for practice were formulated, focusing on how
information professionals can best facilitate OT students' learning and evidence
based research skills in preparation for clinical practice. The study was
completed by Jane Morgan-Daniel, who received a Distinction for her work from
Aberystwyth University, where she graduated with an MSC in Information and
Library Studies in December 2016. She has written this article together with her
dissertation supervisor, Hugh Preston. A. M.
PMID- 28488808
TI - Cracking induction in health libraries: is there a right way?
AB - In most instances, inductions are the first time that users will be introduced to
health library services. The time available in which to deliver library
orientation sessions within a broader, Trust induction programme is often
limited, and this can present challenges for health librarians. Inductions are a
great marketing tool, and it is important that induction sessions make the right
impact. Within a brief window of opportunity, the health librarian must impart
key information to the inductees whilst ensuring the session is relevant and
memorable. In this article, guest writer Nicola Healey, Library Manager of North
Somerset Healthcare Library, discusses the range of approaches she and her
colleagues have explored in delivering library inductions, explaining what
worked, what did not and what areas still remain for development. H. S.
PMID- 28488809
TI - Optimized isolation and expansion of human airway epithelial basal cells from
endobronchial biopsy samples.
AB - Autologous airway epithelial cells have been used in clinical tissue-engineered
airway transplantation procedures with a view to assisting mucosal regeneration
and restoring mucociliary escalator function. However, limited time is available
for epithelial cell expansion due to the urgent nature of these interventions and
slow epithelial regeneration has been observed in patients. Human airway
epithelial cells can be expanded from small biopsies or brushings taken during
bronchoscopy procedures, but the optimal mode of tissue acquisition from patients
has not been investigated. Here, we compared endobronchial brushing and
endobronchial biopsy samples in terms of their cell number and their ability to
initiate basal epithelial stem cell cultures. We found that direct co-culture of
samples with 3T3-J2 feeder cells in culture medium containing a Rho-associated
protein kinase inhibitor, Y-27632, led to the selective expansion of greater
numbers of basal epithelial stem cells during the critical early stages of
culture than traditional techniques. Additionally, we established the benefit of
initiating cell cultures from cell suspensions, either using brushing samples or
through enzymatic digestion of biopsies, over explant culture. Primary epithelial
cell cultures were initiated from endobronchial biopsy samples that had been
cryopreserved before the initiation of cell cultures, suggesting that
cryopreservation could eliminate the requirement for close proximity between the
clinical facility in which biopsy samples are taken and the specialist laboratory
in which epithelial cells are cultured. Overall, our results suggest ways to
expedite epithelial cell preparation in future airway cell therapy or
bioengineered airway transplantation procedures.
PMID- 28488810
TI - One gene, multiple alleles: insights into the microevolution of pigmentation
polymorphisms.
AB - Understanding how phenotypic variation is generated and maintained, and the
evolutionary forces that shape these processes is the main goal of evolutionary
biology. Great progress has been made in uncovering the genetic basis of
morphological diversity, yet little is known about both the genetics and
developmental basis of discrete polymorphisms segregating in wild populations.
Exploring variation in developmental mechanisms at the population level can
address the long-standing question of whether the mechanisms of change are the
same at the micro- and macroevolutionary scale. This integration has been
difficult mainly because the study of the evolution of developmental mechanisms
and population genetics remain separate (Genetics, 195, 625 and 2013). In this
issue of Molecular Ecology, Roberts et al. (Molecular Ecology and 2017) make a
significant contribution towards bridging this gap by studying the genetic and
developmental basis of an extremely variable pigmentation pattern. A polymorphic
blotched coloration is common among females of four genera of Lake Malawi
cichlids. The presence of this phenotype associates with a noncoding SNP upstream
of the transcription factor pax7a (Science, 326, 998 and 2009). The authors
describe in detail the morphs' pigmentation development, showing that phenotypic
differences result from alterations in pigment cell development and survival.
Next, using controlled crosses and population genetics studies, they identified
three putative pax7a dominant blotch alleles that are associated with specific
morphs. These different alleles lead to higher levels of pax7a transcript that
correlate with different pigment cell composition. Finally, sequence comparison
of the locus within populations and between species revealed a common origin of
the allele controlling the blotched morph followed by a pattern of sequential
appearance of derived alleles that gave rise to morph diversity. The coupling of
the evolutionary history of this allelic series with the developmental analysis
of the phenotype paves the way for a mechanistic understanding of morphological
innovation and diversification.
PMID- 28488811
TI - Resolution of Occlusive Carotid Artery Thrombus Treated with Anticoagulation as
Demonstrated on Duplex Ultrasonography.
AB - BACKGROUND AND PURPOSE: While the majority of cerebral ischemic events due to
carotid occlusive disease result from atherosclerotic plaque rupture,
intraluminal carotid artery thrombus occasionally occurs in patients without
preexisting carotid atherosclerosis. Identification of nonatherosclerotic
thrombus as the cause of the carotid occlusive disease can obviate the need for
an interventional procedure, and resolution of thrombus can be monitored with B
mode duplex ultrasonography. METHODS: We reviewed 3 patients treated on The Mount
Sinai Hospital Stroke Unit with anticoagulation for nonatherosclerotic carotid
thrombi and followed with serial Doppler ultrasonogrpahy for resolution of
thrombus. RESULTS: Occlusive carotid thrombus was successfully treated in all 3
patients with systemic anticoagulation. B-mode duplex ultrasonography allowed for
demonstration of resolving thrombus. CONCLUSION: Differentiation between a
stenotic plaque and occlusive thrombus can be achieved by ultrasonographic
analysis of thrombus morphology, attachment site potential, and characteristics
of a resolving thrombus. Systemic anticoagulation can safely and effectively
eliminate the risk for future embolization and complete occlusion of the carotid
artery in patients who present with transient ischemic events or completed
infarcts of small size.
PMID- 28488812
TI - Decreased body mass index is associated with impaired survival in lung cancer
patients with brain metastases: A retrospective analysis of 624 patients.
AB - Body mass index (BMI) is a prognostic factor in several cancer types. We
investigated the prognostic role of BMI in a large patient cohort with newly
diagnosed lung cancer brain metastases (BM) between 1990 and 2013. BMI at
diagnosis of BM and graded prognostic assessment (GPA) were calculated.
Definitions were underweight (BMI <18.50), weight within normal range (BMI 18.50
24.99) and overweight (BMI >= 25.00). A total of 624 patients (men 401/624
[64.3%]; women 223/624 [35.7%]; median age of 61 [range 33-88]) were analysed.
Histology was non-small cell lung cancer in 417/622 (66.8%), small cell lung
cancer (SCLC) in 205/624 (32.9%) and not otherwise specified in 2/624 (0.3%)
patients. About 313/624 (50.2%) had normal BMI, 272/624 (43.5%) were overweight
and 39/624 (6.3%) were underweight. Underweight patients had shorter median
overall survival (3 months) compared to patients with normal BMI (7 months) and
overweight (8 months; p < .001; log rank test). At multivariate analysis, higher
GPA class (HR 1.430; 95% cumulative incidence, CI 1.279-1.598; p < .001; Cox
regression model), SCLC histology (HR 1.310; 95% CI 1.101-1.558) and presence of
underweight (HR 1.845; 95% CI 1.317-2.585; p = .014; Cox regression model) were
independent prognostic factors. Underweight at diagnosis of BM in lung cancer is
associated with an unfavourable prognosis.
PMID- 28488813
TI - Imaging mass spectrometry for metabolites: technical progress, multimodal
imaging, and biological interactions.
AB - Imaging mass spectrometry (IMS) allows the study of the spatial distribution of
small molecules in biological samples. IMS is able to identify and quantify
chemicals in situ from whole tissue sections to single cells. Both vacuum mass
spectrometry (MS) and ambient MS systems have advanced considerably over the last
decade; however, some limitations are still hard to surmount. Sample
pretreatment, matrix or solvent choices, and instrument improvement are the key
factors that determine the successful application of IMS to different samples and
analytes. IMS with innovative MS analyzers, powerful MS spectrum databases, and
analysis tools can efficiently dereplicate, identify, and quantify natural
products. Moreover, multimodal imaging systems and multiple MS-based systems
provide additional structural, chemical, and morphological information and are
applied as complementary tools to explore new fields. IMS has been applied to
reveal interactions between living organisms at molecular level. Recently, IMS
has helped solve many previously unidentifiable relations between bacteria,
fungi, plants, animals, and insects. Other significant interactions on the
chemical level can also be resolved using expanding IMS techniques. WIREs Syst
Biol Med 2017, 9:e1387. doi: 10.1002/wsbm.1387 For further resources related to
this article, please visit the WIREs website.
PMID- 28488814
TI - iPhos-PseEvo: Identifying Human Phosphorylated Proteins by Incorporating
Evolutionary Information into General PseAAC via Grey System Theory.
AB - Protein phosphorylation plays a critical role in human body by altering the
structural conformation of a protein, causing it to become activated/deactivated,
or functional modification. Given an uncharacterized protein sequence, can we
predict whether it may be phosphorylated or may not? This is no doubt a very
meaningful problem for both basic research and drug development. Unfortunately,
to our best knowledge, so far no high throughput bioinformatics tool whatsoever
has been developed to address such a very basic but important problem due to its
extremely complexity and lacking sufficient training data. Here we proposed a
predictor called iPhos-PseEvo by (1) incorporating the protein sequence
evolutionary information into the general pseudo amino acid composition (PseAAC)
via the grey system theory, (2) balancing out the skewed training datasets by the
asymmetric bootstrap approach, and (3) constructing an ensemble predictor by
fusing an array of individual random forest classifiers thru a voting system.
Rigorous jackknife tests have indicated that very promising success rates have
been achieved by iPhos-PseEvo even for such a difficult problem. A user-friendly
web-server for iPhos-PseEvo has been established at http://www.jci
bioinfo.cn/iPhos-PseEvo, by which users can easily obtain their desired results
without the need to go through the complicated mathematical equations involved.
It has not escaped our notice that the formulation and approach presented here
can be used to analyze many other problems in protein science as well.
PMID- 28488816
TI - Characterization of Methyltransferase AlmCII in Chalcomycin Biosynthesis: The
First TylF Family O-Methyltransferase Works on a 4'-Deoxysugar.
AB - Sugar O-methylation is a ubiquitous modification in natural products and plays
diverse roles. This realization has inspired many attempts to search for novel
methyltransferases. Chalcomycins are a group of 16-membered macrolides containing
two methylated sugars that require three methyltransferases for their
biosynthesis. Here, we identified that AlmCII, a sugar O-methyltransferase
belonging to the TylF family that was previously only known to methylate sugars
with a 4'-hydroxy group, can methylate a 4',6'-dideoxysugar during the
biosynthesis of chalcomycins. An in vitro enzymatic assay revealed that AlmCII is
divalent metal-dependent with an optimal pH of 8.0 and optimal temperature of 42
degrees C. Moreover, the 3'-O-demethylated chalcomycins exhibit less than 6 % of
the antibacterial activity of their parent compounds. This is the first report
demonstrating that a TylF family O-methyltransferase can use a 4'-deoxy sugar as
a substrate and highlighting the importance of this methylation for the
antibacterial activity of chalcomycins.
PMID- 28488815
TI - Hypomorphic conditional deletion of E11/Podoplanin reveals a role in osteocyte
dendrite elongation.
AB - The transmembrane glycoprotein E11/Podoplanin (Pdpn) has been implicated in the
initial stages of osteocyte differentiation. However, its precise function and
regulatory mechanisms are still unknown. Due to the known embryonic lethality
induced by global Pdpn deletion, we have herein explored the effect of bone
specific Pdpn knockdown on osteocyte form and function in the post-natal mouse.
Extensive skeletal phenotyping of male and female 6-week-old Oc-cre;Pdpnflox/flox
(cKO) mice and their Pdpnflox/flox controls (fl/fl) has revealed that Pdpn
deletion significantly compromises tibial cortical bone microarchitecture in both
sexes, albeit to different extents (p < 0.05). Consistent with this, we observed
an increase in stiffness in female cKO mice in comparison to fl/fl mice (p <
0.01). Moreover, analysis of the osteocyte phenotype by phalloidin staining
revealed a significant decrease in the dendrite volume (p < 0.001) and length (p
< 0.001) in cKO mice in which deletion of Pdpn also modifies the bone anabolic
loading response (p < 0.05) in comparison to age-matched fl/fl mice. Together,
these data confirm a regulatory role for Pdpn in osteocyte dendrite formation and
as such, in the control of osteocyte function. As the osteocyte dendritic network
is known to play vital roles in regulating bone modeling/remodeling, this
highlights an essential role for Pdpn in bone homeostasis.
PMID- 28488817
TI - Neladenoson Bialanate Hydrochloride: A Prodrug of a Partial Adenosine A1 Receptor
Agonist for the Chronic Treatment of Heart Diseases.
AB - Adenosine is known to be released under a variety of physiological and
pathophysiological conditions to facilitate the protection and regeneration of
injured ischemic tissues. The activation of myocardial adenosine A1 receptors (A1
Rs) has been shown to inhibit myocardial pathologies associated with ischemia and
reperfusion injury, suggesting several options for new cardiovascular therapies.
When full A1 R agonists are used, the desired protective and regenerative
cardiovascular effects are usually overshadowed by unintended pharmacological
effects such as induction of bradycardia, atrioventricular (AV) blocks, and
sedation. These unwanted effects can be overcome by using partial A1 R agonists.
Starting from previously reported capadenoson we evaluated options to tailor A1 R
agonists to a specific partiality range, thereby optimizing the therapeutic
window. This led to the identification of the potent and selective agonist
neladenoson, which shows the desired partial response on the A1 R, resulting in
cardioprotection without sedative effects or cardiac AV blocks. To circumvent
solubility and formulation issues for neladenoson, a prodrug approach was
pursued. The dipeptide ester neladenoson bialanate hydrochloride showed
significantly improved solubility and exposure after oral administration.
Neladenoson bialanate hydrochloride is currently being evaluated in clinical
trials for the treatment of heart failure.
PMID- 28488818
TI - Emerging Global Health Issues: A Nurse's Role
PMID- 28488819
TI - Simulating Complex Community Disaster Preparedness: Collaboration for Point of
Distribution
PMID- 28488820
TI - The Zika Virus Epidemic: Public Health Roles for Nurses
PMID- 28488821
TI - Prevention and Control of Worldwide Mosquito-Borne Illnesses: Nurses as Teachers
PMID- 28488822
TI - United States Public Health Service Nurses: Deployment in Global Crisis
PMID- 28488823
TI - Intra-system reliability of SICS: video-tracking system (Digital.Stadium(r)) for
performance analysis in soccer.
AB - BACKGROUND: The correct evaluation of external load parameters is a key factor in
professional soccer. The instrumentations usually utilised to quantify the
external load parameters during official matches are video-tracking systems
(VTS). VTS is a technology that records two-dimensional position data (x and y)
at high sampling rates (over 25 Hz). The aim of this study was to evaluate the
intra-system reliability of Digital.Stadium(r) VTS. METHODS: Twenty-eight
professional male soccer players taking part in the Italian Serie A (age 24+/-6
years, body mass 79.5+/-7.8 kg, stature 1.83+/-0.05 m) during the 2015/16 season
were enrolled in this study (team A and team B). Video-analysis was done during
an official match and data analysis was performed immediately after the game
ended and then replicated a week later. RESULTS: This study reported a near
perfect relationship between the initial analysis (analysis 1) and the replicated
analysis undertaken a week later (analysis 2). R2 coefficients were highly
significant for each of the performance parameters, P<0.001. This study reported
a mean TD=8095+/-3271 and 8073+/-3263 m in analysis 1 and analysis 2,
respectively. Players reported a mean distance covered over 25 w kg-1 equivalent
to 1304+/-673 m and 1294+/-672 m, and they reported a mean metabolic power of
9.65+/-1.64 w kg-1 and 9.58+/-1.61 w kg-1, in analysis 1 and analysis 2,
respectively. CONCLUSIONS: The findings reported in this study underlined that
all data reported by Digital.Stadium(r) VTS showed high levels of absolute and
relative reliability.
PMID- 28488824
TI - Effects of verbal encouragement on force and electromyographic activations during
exercise.
AB - BACKGROUND: The aim of the present study was to examine the effects of verbal
encouragement on isometric force and associated electromyographic (EMG)
parameters during a handgrip task. METHODS: Twenty-three participants (12 women
and 11 men) performed maximal voluntary isometric handgrip contractions following
three conditions: 1) verbal encouragement (VE) condition: participants executed
isometric contractions while being verbally encouraged; 2) non-verbal
encouragement (nVE) condition: the same starting and stopping signal but without
encouragement; 3) non-concentration and non-motivation (nCM) condition: self
initiated contractions without concentration and motivation. Start and stop of
the contraction were self-initiated. The maximal voluntary force (MVF) and the
maximal rate of force development (MRFD) were measured. Integrated EMG
corresponding to MVF (iEMGMVF) and to MRFD (iEMGMRFD) were collected from flexor
digitorum superficialis (FDS) and extensor digitorum communis (EDC) muscles.
RESULTS: MVF was higher during VE compared with nVE (+11.7%; P<0.05) and nCM
(+23.2%; P<0.05) conditions. Likewise, MRFD was significantly higher during VE,
compared with nVE (+21.7%; P<0.05) and nCM (+55.4%; P<0.05) conditions. iEMGMVF
increased for FDS and EDC during VE, compared to nVE (+26.19%, +20.5%) and nCM
conditions (+68.85%, +48.91%), respectively. iEMGMRFD increased for FDS and EDC
during VE, compared to nVE (+21.2%, +46.07%) and nCM conditions (+23.79%,
+42.32%). Furthermore, the reproducibility of all these indices was higher with
VE condition. CONCLUSIONS: Taken together, force production (MVF and MRFD) and
EMG data supported the view that muscles activity is considerably influenced by
the verbal encouragements during isometric force exercise.
PMID- 28488825
TI - A randomized trial of the effects of an aquatic exercise program on depression,
anxiety levels, and functional capacity of people who suffered an ischemic
stroke.
AB - BACKGROUND: Aquatic exercise programs are used in rehabilitation and might help
to reduce disability after stroke. This was a randomized intervention trial to
assess the influence of an aquatic exercise program on people suffering from
depression and anxiety after ischemic stroke. METHODS: Participants were
randomized to an experimental group (EG) composed of 19 individuals (51.8+/-8.5
years; ten males and nine females), and a control group (CG) composed of 17
people (52.7+/-6.7 years; nine males and eight females). The aquatic exercise
program consisted of two sessions per week, each lasting between 45 and 60
minutes and divided into 5 to 10 minutes exercise sections during 12 weeks. The
State-Trait Anxiety Inventory was used to determine anxiety levels while the Beck
Depression Inventory was used as a self-assessment of depression. RESULTS: EG
improved measures of depression, anxiety trait and anxiety state between pre- and
post-treatment, with no changes in CG. EG improved in all tests related to
functional capacity compared to CG. CONCLUSIONS: The practice of aquatic
exercises promotes improvements in the levels of depression and anxiety in people
who suffered an ischemic stroke.
PMID- 28488826
TI - Soccer training: high-intensity interval training is mood disturbing while small
sided games ensure mood balance.
AB - BACKGROUND: The aim of the study was to compare the effects of high-intensity
intermittent training (HIIT) versus small-sided games (SSG) in soccer on both the
physiological responses and the mood state of players. METHODS: Sixteen
professional soccer players took part in the study (age: 24.1+/-0.9 years).
Testing of players was conducted on separate days in a randomized and counter
balanced order (each training session: 28 minutes: 4x4 minutes work with 3
minutes of passive recovery in-between). Effort: HIIT: intermittent 15-s runs at
110% maximal aerobic speed with 15 seconds of passive recovery in-between. SSG: 4
versus 4 players on a 25x35 meter pitch size with full-involvement play.
Psychological responses before and after each training-session were assessed
using the profile of mood-state (POMS: Tension, Depression, Anger, Vigor,
Fatigue, and Confusion). The players' heart rate (HR) was continuously measured,
whereas ratings of perceived exertion (RPE) and blood lactate concentration
([La]) were collected ~3-min after each training-session. RESULTS: HIIT and SSG
showed no significant difference in HR, RPE and [La] responses. The HIIT compared
with SSG resulted in: an increased total mood disturbance (P<0.001), tension
(P<0.05), fatigue (P<0.01) and a decreased vigor (P<0.001). CONCLUSIONS: Both
HIIT and SSG sessions induced similar physiological responses, in contrast, HIIT
produced a mood disturbance while SSG ensured mood balance. Practitioners could
choose between these two exercises according to the objective of their training,
keeping in mind the mood-related advantages of the SSG shown in the present
study.
PMID- 28488827
TI - Water versus land-based exercises as physical training programs in elderly.
AB - BACKGROUND: The study aims to analyze and quantify the improvements of some
physical skills in a group of subjects over 65 years old who practice regular
activities in the gym and in a microgravity environment. METHODS: The study
included 132 subjects (68.9+/-5.5 years, 72.7+/-14.4 kg, 155.3+/-9.2, 30.6+/-5
kg/m2) who perform regular physical activity adapted and controlled for the
elderly twice a week (50' per session) for a period of 8 months. The tests
evaluate flexibility, abdominal and leg strength and balance. The groups, in
baseline, are homogeneous between them to anthropometric parameters and the
initial performance of motor skills analyzed. A mixed between-within subject
ANOVA was conducted to assess the impact of the training regimens. Data from this
study showed an increase in muscular strength (leg and abdominal muscles), body
balance and muscular flexibility after 8 months of both training methods.
RESULTS: Both experimental groups had significant improvements in motor skills
considered and interesting results were observed in water activity, overall, in
balance (+66%, P<0.001) and abdominal muscular strength (+16%, P<0.001) where the
water group showed a significant within and between improvement. CONCLUSIONS:
Current results indicate that the water and land programs improved motor skills
in the elderly. Furthermore, when the effectiveness of the training programs was
compared, it was verified that the water group has recorded major changes,
overall on abdominal strength and balance test statistically significant versus
the land group.
PMID- 28488828
TI - Effects of active recovery during interval training on plasma catecholamines and
insulin.
AB - BACKGROUND? Active recovery has been used as a method to accelerate the recovery
during intense exercise. It also has been shown to improve performance in
subsequent exercises, but little is known about its acute effects on the hormonal
and metabolic profile. The aim of this research was to study the effects of
active recovery on plasma catecholamines and plasma insulin during a high
intensity interval exercise. METHODS? Seven subjects performed two high-intensity
interval training protocols which consisted of three 30-second high-intensity
bouts (constant intensity), separated by a recovery of 4 minutes. The recovery
was either active recovery or passive recovery. During the main test blood
samples were collected and plasma insulin, plasma catecholamines and blood
lactate were determined. Furthermore, respiratory gasses were also measured.
RESULTS? Plasma insulin and blood lactate were significantly higher in the
passive recovery trial, while plasma adrenaline was higher in the active
recovery. Additionally, VO2 and VCO2 were significantly more increased during the
active recovery trials. CONCLUSIONS? These results suggest that active recovery
affects the hormonal and metabolic responses to high-intensity interval exercise.
Active recovery produces a hormonal environment which may favor lipolysis and
oxidative metabolism, while passive recovery may be favoring glycolysis.
PMID- 28488829
TI - Analyzing the relationship between anthropometric and motor indices with
basketball specific pre-planned and non-planned agility performances.
AB - BACKGROUND: Although agility is an important quality in basketball, factors
associated with basketball specific pre-planned-agility (change-of-direction
speed, CODS) and non-planned-agility (reactive agility, RA) are rarely
investigated. The aim of this study was to evaluate relationship between
anthropometric and motor indices with basketball-specific CODS and RA in male
basketball players of high performance level. METHODS: We tested 88 high-level
male basketball players (height: 194.62+/-8.09 cm; body mass: 89.13+/-10.81 kg;
age: 21.12+/-3.47 years). The sample was randomly divided into validation (N.=44)
and cross-validation (N.=44) subsamples. The study variables included: broad
jump, countermovement-jump, reactive-strength-index, visual-reaction-time, body
height, body mass, and body fat percentage (predictors); as well as basketball
specific CODS and RA (criteria). Univariate associations were assessed by
Pearson's correlation coefficients. Multivariate relationships between the
predictors and the criteria were assessed with multiple regression analysis for
the validation subsample, which was then cross-validated. RESULTS: The
established multiple regression models were successfully cross-validated for CODS
(R2=0.40 and 0.36; P=0.01) and RA (R2=0.38 and 0.41; P=0.01, for validation and
cross-validation subsample, respectively). The broad-jump (i.e., horizontal
displacement) is important predictor of CODS (Beta=-0.41; P=0.01);
anthropometrics and body build are specifically associated with RA (Beta=0.51,
0.61 and 0.41 for body height, body mass and body fat percentage, respectively;
all P<0.05), while reactive-strength-index is directly related both to CODS
(Beta=-0.41, P=0.02), and RA (Beta=-0.40, P=0.03). CONCLUSIONS: While basketball
players are differentially oriented toward specific game duties, specific
capacities should be developed in order to meet specific sport requirements.
PMID- 28488830
TI - Match outcome and sprinting activities in match play by elite German soccer
players.
AB - BACKGROUND: The aim of the study was to examine the ways playing positions and
match outcome (i.e. win, draw, loss) affect the sprint distance covered and the
number of sprints performed by German Bundesliga soccer players. METHODS: Match
performance data were collected from 350 soccer players competing in the German
Bundesliga during the 2014/2015 domestic season. A total of 4393 individual match
observations were undertaken on outfield players. The analysis was carried using
the Impire AG motion analysis system with records of all movements of players in
all the 306 matches. The recorded variables included total sprint distance
covered and the total number of sprints in offensive and defensive play. The
conformity assessment was carried out with the Shapiro-Wilk test (P<=0.01). To
compare mean values of the examined variables a two-way ANOVA was used. The
differences between pairs of means were verified with Fisher's LSD. RESULTS: The
analysis of the covered sprint distance and the number of performed sprints
showed that central defenders and full-backs covered shorter distances in won
matches than in lost matches (P<=0.05). Furthermore, forwards and wide
midfielders covered significantly longer sprint distances in won matches than in
lost matches (P<=0.05). CONCLUSIONS: The match outcome may be viewed as a measure
of performance accomplishment and, hence, it may influence the sprinting efforts
made by players.
PMID- 28488831
TI - Reduced leptin level is independent of fat mass changes and hunger scores from
high-intensity intermittent plus strength training.
AB - BACKGROUND: This study aimed to analyze the effects of high-intensity
intermittent training (HIIT) plus strength training on body composition, hormone
related to energy balance (leptin), and hunger scores in physically active non
obese men. METHODS: Sixteen men were allocated in two different groups, training
group (N.=10) performed a combined HIIT (5 km, 1 minute of effort interspersed by
1 minute of rest in passive recovery) followed by strength exercise session
(three sets, with load of 8-12 repetition maximum) twice a week, during 8 weeks,
while control group (N.=6) did not suffer any intervention. Hunger scores, leptin
concentrations and body composition were assessed. Body composition, fasting
leptin and hunger score were compared through two-way analysis (group and period)
with repeated measures in the second factor while leptin and hunger scores in
exercise session pre- and post-8 weeks through two-way analysis (period and time
of measurement) with repeated measures in the second factor. RESULTS: The fasting
leptin decreased pre- to post-8week in training group (7.7+/-4.9 to 2.9+/-2.1
ng/mL; P=0.012). For leptin response to exercise session there was main effect of
training period, with higher values pre- (6.5+/-3.9 ng/mL) than post-training
(2.6+/-2.1 ng/mL; P<0.001). For hunger scores there was effect of time of
measurement (P<0.001), decreasing after breakfast and increasing over the
experiment. CONCLUSIONS: Combined HIIT plus strength training were able to
promote alterations in a hormone related to energy balance independent of body
composition and hunger index alterations in physically active non-obese men.
PMID- 28488832
TI - Road to the Olympics: physical fitness of medalists of the Canoe Sprint Junior
European and World Championship events over the past 20 years.
AB - BACKGROUND: In this article we aimed to find out whether there is a difference in
physiological, anthropometric and power variables between medalists in junior
international Championship events (MJCH) and the remaining members of the
national team (NT) in flat water canoe sprint. METHODS: Sixty male junior
kayakers from Slovak NT were tested annually between years 1995 and 2016. Sixteen
of them won at least one medal (gold, silver or bronze) at junior international
Championship. Exercise capacity assessment on treadmill running (TR) and kayak
ergometer (KE), anthropometric and muscle power measurements were performed
between years 1995 and 2016. RESULTS: MJCH were on average by 10% better in TR
speed and KE power output at VO2max than the rest of NT (19.72+/-0.8 vs. 18+/-1.0
km.h-1, P<0.01, ES=1.84; 206.6+/-21.5 vs. 182.3+/-25.5 W, P<0.01, ES=0.99,
respectively). Similarly mean maximal power in bench press and bench pull was
higher in MJCH (522.9+/-72.0 vs. 464.3+/-69.0 W, P<0.01; ES=0.84; 629.15+/-63.3
vs. 571.6+/-58.7 W, P<0.01; ES=0.96, respectively). CONCLUSIONS: These data show
that an athlete has to be on average by 10% better in physical fitness than the
rest of NT to take podium position at canoe sprint junior international
Championship. Prosperous juniors are further successful at senior Championship
events and Olympics. We assume that high level of physical fitness in junior age
is not a guarantee but a prerequisite for a successful future career.
PMID- 28488833
TI - The feasibility of an exercise program 12 months post-stroke in a small urban
community.
AB - BACKGROUND: There are few community-based exercise programs catering to
individuals post-stroke, despite an increasing need. The primary objective of
this study was to assess the feasibility of running a community-based exercise
program for individuals post-stroke, and to provide a framework for local
communities to run similar programs. METHODS: Individuals who had a stroke within
12 months of the start of the program were eligible to participate in a 9-week
community-based exercise program. Sit to stand, grip strength, arm curl, timed up
and-go, 6-minute walk, Berg Balance Scale, Stroke-Specific Quality of Life
Questionnaire, and Exercise Self-Efficacy Scale were assessed pre- and post
program to determine the effectiveness of the program. Caregivers of participants
were invited to participate in a focus group after the program (N.=5) to better
understand program feasibility and areas for improvement. RESULTS: Individuals (9
males, 1 female) with stroke were recruited from a local rehabilitation program
within 1 week (aged 72.7+/-9.3 years). The ratio of volunteers to participants
was 1:2. All participants completed the exercise program and pre-post-testing.
Significant improvements were observed for sit to stand (7.6+/-3.4 to 9.8+/-4.3
repetitions, P<0.01), grip strength of the non-affected side (29.7+/-8.9 to
32.6+/-8.3 lbs, P=0.04), arm curl (15.2+/-6.1 to 19.9+/-4.7 repetitions, P=0.04),
and Exercise Self-Efficacy score (Z=2.50, P=0.01, r=0.79) from pre to post
program. Caregivers suggested increasing the frequency of the program.
CONCLUSIONS: An effective community-based exercise program for individuals post
stroke can be run at community centers utilizing qualified volunteers.
PMID- 28488834
TI - The efficacy of wearable activity tracking technology as part of a weight loss
program: a systematic review.
AB - INTRODUCTION: The world obesity rate has increased over the past two decades.
This problem has been linked to inactivity and lack of exercise among individuals
which prompted the development of wearable activity tracking technology. This
technology is commonly offered as a bracelet, watch, or pendent that provides
feedback of daily activity such as total step count, heart rate, and energy
expenditure. Despite the popularity of these devices, their efficacy to assist in
behavior change and weight loss is still being studied. The purpose of this
systematic review was to appraise the current evidence on the efficacy of
wearable activity devices when used in a comprehensive weigh loss program.
EVIDENCE ACQUISITION: A systematic review was conducted according the PRISMA
guidelines. A search of electronic databases was conducted through December 2016
using the following keywords: activity monitor, consumer, wearable, technology,
Fitbit(r), Garmin(r), Jawbone(r), physical, activity, tracker, weight loss,
walking, pedometer, accelerometer, step count, calories, obesity, digital, self
monitoring, and mobile health (mHealth). The grading of studies was conducted
using the PEDro scale. EVIDENCE SYNTHESIS: We identified 7184 citations, 25 met
the inclusion criteria. Twenty-one studies scored a 6 or higher and four studies
scored a 5 on the PEDro scale. All subjects had a Body Mass Index (BMI) of >=25
kg/m2 and were mostly women. CONCLUSIONS: The results suggests that short-term
(<6 months) weight loss interventions using activity trackers may be a better
option than a standard weight loss program in middle age or older adults. Younger
adults may not benefit from such technology.
PMID- 28488835
TI - Incidence of injury and illness in South African professional male soccer
players: a prospective cohort study.
AB - BACKGROUND: Medical illnesses and sports-related injuries both have an effect on
athlete health and performance. Epidemiology of injury and illness has been
extensively researched during international soccer tournaments and the European
soccer season. Reports on injury location and severity differ across geographical
regions, and there is limited information on injury epidemiology in African
soccer leagues. No studies have investigated the illness burden in soccer in
Africa. METHODS: This was a prospective cohort study involving two soccer teams
over the 10-month duration of the 2015/16 Premier Soccer League in South Africa.
Team medical staff recorded daily soccer exposure, illness and injuries. Team
based match and training exposure was calculated and used to determine injury and
illness incidence and burden over the soccer season. RESULTS: Overall injury
incidence was 2.2/1000 hours, with match injury incidence of 24.8/1000 hours and
training injury incidence of 0.9/1000 hours. Time loss injuries accounted for 33
of the 44 injuries recorded. The most common time loss injury location was the
knee (14 injuries, 42%). There were 7 minimal, 4 mild, 12 moderate and 10 severe
injuries. Sprain/ligament injury (8 injuries) was the most common type, followed
by meniscus/cartilage injury (7 injuries). Eleven illnesses were reported during
the season, with an incidence of 0.7/1000 player days, and most were minimal in
severity (8/11). The illness burden was 1.7/1000 player days. The respiratory
(46%) and gastrointestinal (36%) systems were most commonly affected.
CONCLUSIONS: The incidence of injury was comparable with data reported
internationally and mirrors the increased risk of injury during matches versus
training. The nature of injury differed in that the knee was more frequently
affected than the ankle or thigh, joint injuries were more common than muscle
injuries, and there was a larger proportion of severe injuries. The illness
burden was very low.
PMID- 28488836
TI - Effects of low-load resistance exercise with blood flow restriction on
intramuscular hemodynamics, oxygenation level and water content.
AB - BACKGROUND: Muscle metabolism during and after low-load blood flow restriction
(BFR) exercise should be further investigated to clarify the mechanism by which
the exercise leads to muscle hypertrophy, and increases strength and endurance.
We aimed to investigate the effects of low-load resistance exercise with BFR on
intramuscular hemodynamics, oxygenation level, and water content. METHODS: Seven
men performed ankle plantar flexion exercise (120 repetitions, 30% one repetition
maximum) using a custom-made device with and without BFR inside a magnetic
resonance scanner. Changes in the total hemoglobin/myoglobin concentration and
Tissue Oxygenation Index (TOI) within the medial gastrocnemius were evaluated
before, during, and after exercise using near-infrared spectroscopy.
Intramuscular water content was evaluated before and after exercise by
calculating an apparent diffusion coefficient (ADC) using magnetic resonance
diffusion-weighted imaging. RESULTS: The TOI significantly decreased during BFR
and non-restricted exercises, and significantly increased after BFR exercise;
compared to the non-restricted condition, the BFR condition showed significantly
greater changes in the TOI during and after exercise. The total
hemoglobin/myoglobin concentration significantly increased during and after
exercise in both exercise conditions; the BFR condition temporarily showed
significantly greater values during and after exercise. Although the ADC values
significantly elevated after BFR and non-restricted exercises, the elevation was
significantly greater in the BFR condition. CONCLUSIONS: Compared to non
restricted exercise, low-load BFR exercise exposes an exercising muscle to
greater hypoxic and hyperemic environments. Moreover, BFR exercise not only
elevates muscle oxygenation level, but also results in greater muscle swelling
and reactive hyperemia than those observed after non-restricted exercise.
PMID- 28488837
TI - Allometric associations between body size, shape, and 100-m butterfly speed
performance.
AB - BACKGROUND: This study aimed to estimate the optimal body size, limb-segment
length, and girth or breadth ratios associated with 100-m butterfly speed
performance in swimmers. METHODS: One-hundred-sixty-seven swimmers as subjects
(male: N.=103; female: N.=64). Anthropometric measurements comprised height, body
mass, skinfolds, arm-span, upper-limb-length, upper-arm, forearm, hand-lengths,
lower-limb-length, thigh-length, leg-length, foot-length, arm-relaxed-girth,
forearm-girth, wrist-girth, thigh-girth, calf-girth, ankle-girth, biacromial and
biiliocristal-breadths. To estimate the optimal body size and body composition
components associated with 100-m butterfly speed performance, we adopted a
multiplicative allometric log-linear regression model, which was refined using
backward elimination. RESULTS: Fat-mass was the singularly most important whole
body characteristic. Height and body-mass did not contribute to the model. The
allometric model identified that having greater limb segment length-ratio (arm
ratio = [arm-span]/[forearm]) and limb girth-ratio (girth-ratio = [calf
girth]/[ankle-girth]) were key to butterfly speed performance. A greater arm-span
to forearm-length ratio and a greater calf to ankle-girth-ratio suggest that a
combination of larger arm-span and shorter forearm-length and the combination of
larger calves and smaller ankles-girth may benefit butterfly swim speed
performance. In addition having greater biacromial and biliocristal breadths is
also a major advantage in butterfly swimming speed performance. Finally, the
estimation of these ratios was made possible by adopting a multiplicative
allometric model that was able to confirm, theoretically, that swim speeds are
nearly independent of total body size. CONCLUSIONS: The 100-m butterfly speed
performance was strongly negatively associated with fat mass and positively
associated with the segment length ratio (arm-span/forearm-length) and girth
ratio (calf-girth)/(ankle-girth), having controlled for the developmental changes
in age.
PMID- 28488838
TI - Caring for Patients with Service Dogs: Information for Healthcare Providers
AB - People with disabilities use various assistance devices to improve their capacity
to lead independent and fulfilling lives. Service dogs can be crucial lifesaving
companions for their owners. As the use of service dogs increases, nurses are
more likely to encounter them in healthcare settings. Service dogs are often
confused with therapy or emotional support dogs. While some of their roles
overlap, service dogs have distinct protection under the American Disabilities
Act (ADA). Knowing the laws and proper procedures regarding service dogs
strengthens the abilities of healthcare providers to deliver holistic, patient
centered care. This article provides background information about use of dogs,
and discusses benefits to patients and access challenges for providers. The
author reviews ADA laws applicable to service dog use and potential challenges
and risks in acute care settings. The role of the healthcare professional is
illustrated with an exemplar, along with recommendations for future research and
nursing implications related to care of patients with service dogs.
PMID- 28488839
TI - Nurses Need Not Be Guilty Bystanders: Caring for Vulnerable Immigrant Populations
AB - Nurses face many dilemmas when providing healthcare to immigrants, a vulnerable
population. Racist, rancorous dialogue can create a hostile care environment that
may place patients at risk for substandard care. This article presents a two part
case study about a Hispanic patient to illustrate both examples of inappropriate
dialogue (Part I) and potential nursing actions (Part 2). The authors review
myths versus facts about Hispanic immigrants and introduce activist Thomas
Merton's concept of the guilty bystander, the nursing professional code of
ethics, and Professor Joseph Badaracco's concepts of quiet leadership as
practical tools and approaches that nurses can use to advocate for safe, quality,
ethical care of immigrant populations.
PMID- 28488840
TI - Bladder cancer and Th1 chemokines
AB - Bladder cancer arises from the epithelial lining of the urinary bladder, and it
is known as transitional cell carcinoma (TCC). Tobacco smoking is the main known
contributor to urinary bladder cancer. However thirty percent of bladder tumors
probably result from occupational exposure in the workplace to carcinogens.
Immunotherapy by intravesicular delivery of Bacillus Calmette-Guerin (BCG) is
used to treat and prevent the recurrence of superficial bladder cancer.
Successful BCG immunotherapy for bladder cancer is associated with proper
induction of T helper (Th)1 immunity. In bladder cancer patients after
intravesicular BCG, urine was found to contain high levels of IP-10, and
Interferon (IFN)-gamma. TCC and endothelial cell lines were able to secrete IP-10
in response to BCG or IFN stimulation in vitro. Furthermore intravesicular BCG
induces a cytokine-rich urinary microenvironment that is inhibitory to human
endothelial cells and it is anti-angiogenetic by the induction of Th1 chemokines.
Other studies suggest that therapeutic strategies involving Th1 induction and Th2
dampening may improve responses to immunotherapy. Further studies are needed to
evaluate the IP-10 in circulation, and urine, as prognostic marker of bladder
cancer patients, also in relation to BCG immunotherapy
PMID- 28488841
TI - Catastrophic antiphospholipid syndrome: an update.
AB - Catastrophic antiphospholipid syndrome (CAPS) is a rare variant that accounts for
1% of patients with APS. Despite its low frequency, the mortality-related is very
high ranging from 50% of patients in the first series to 37% in the most recent
data. The current knowledge of this potential devastating entity comes from the
International Registry of patients with CAPS, named CAPS Registry. Small vessel
thrombosis, laboratory features of microangiopathic haemolytic anemia, and
development of multisystem involvement in a very short period of time are the
main characteristics of this syndrome. Clinical manifestations are due to
thrombosis but also, although the evidences are indirect, to excess of
proinflammatory cytokines. Therefore, treatment strategy is based on the
combination of anticoagulation, glucocorticoids, plasma exchange and/or
intravenous immunoglobulins, the so-called triple therapy. In refractory cases or
in those with initial life-threatening situation, rituximab may be an effective
option. Recently, some cases of CAPS have been effectively treated with the
addition of eculizumab to the triple therapy.
PMID- 28488842
TI - Sleep-disordered breathing in heart failure patients after ventricular assist
device implantation and heart transplantation.
AB - Chronic heart failure (CHF) represents a major health and economic burden and is
associated with high rates of hospital admission, morbidity, mortality and
decreased quality-adjusted life years. New advances in the treatment of CHF such
as ventricular assist devices (VADs) and heart transplantation have helped
improve outcomes. Sleep-disordered breathing (SDB) is highly prevalent in CHF
patients and the associated morbidity makes it essential for physicians to be
more cognizant about its existence, interaction and need for treatment. This is a
review of what is known to date about SDB in CHF patients who have undergone
advanced treatments with VADs and/or heart transplantation.
PMID- 28488843
TI - HOTAIR and gastric cancer: a lesson from two meta-analyses.
PMID- 28488844
TI - Magnetic resonance imaging in prostate cancer detection and management: a
systematic review.
AB - INTRODUCTION: The aim of our work was to evaluate the role of multi-parametric
magnetic resonance imaging (mpMRI) in detection and management of prostate cancer
(PC); specifically investigating the efficacy of mpMRI-based biopsy techniques in
terms of diagnostic yield of significant prostate neoplasm and the improved
management of patients who choose conservative treatments or active surveillance.
EVIDENCE ACQUISITION: A systematic and critical analysis through Medline, Embase,
Scopus and Web of Science databases was carried out in March 2016, following the
PRISMA ("Preferred Reporting Items for Systematic Reviews and Meta-Analyses")
statement. The search was conducted using the following key words: "MRI/TRUS
fusion biopsy," "PIRADS," "prostate cancer," "magnetic resonance imaging (MRI),"
"multiparametric MRI (mpMRI)," "systematic prostate biopsy (SB)," "targeted
prostate biopsy (TPB)." English language articles were reviewed for inclusion
ability. EVIDENCE SYNTHESIS: Sixty-six studies were selected in order to evaluate
the characteristics and limitations of traditional sample biopsy, the role of
mpMRI in detection of PC, specifically the increased degree of diagnostic
accuracy of targeted prostate biopsy compared to systematic biopsy (12 cores),
and to transperineal saturation biopsies with trans-rectal ultrasound (TRUS)
only. MpMRI can detect index lesions in approximately 90% of cases when compared
to prostatectomy specimen. The diagnostic performance of biparametric MRI (T2w +
DWI) is not inferior to mpMRI, offering valid options to diminish cost- and time
consumption. Since approximately 10% of significant lesions are still MRI
invisible, systematic cores biopsy seem to still be necessary. The analysis of
the different techniques shows that in-bore MRI-guided biopsy and MRI/TRUS-fusion
guided biopsy are superior in detection of significant PC compared to visual
estimation alone. MpMRI proved to be very effective in active surveillance, as it
prevents underdetection of significant PC and it assesses low-risk disease
accurately. In higher-risk disease, presurgical MRI may change the clinically
based surgical plan in up to a third of cases. CONCLUSIONS: Targeted prostate
biopsy, guided by mpMRI, is able to improve diagnostic accuracy and to reduce the
detection of insignificant PC. Since the negative predictive value (NPV) of mpMRI
is still imperfect, systematic cores biopsy should not be omitted for optimal
staging of disease. A process of a progressive and periodic evolution in the
detection and radiological classification of prostate lesions (such as PIRADS),
is still needed in patients in active surveillance and in radical prostatectomy
planning.
PMID- 28488845
TI - The Babylonian confusion in describing chronic changes in renal allografts.
PMID- 28488846
TI - Impact of Film Thickness of Ultrathin Dip-Coated Compact TiO2 Layers on the
Performance of Mesoscopic Perovskite Solar Cells.
AB - Uniform and pinhole-free electron-selective TiO2 layers are of utmost importance
for efficient perovskite solar cells. Here we used a scalable and low-cost dip
coating method to prepare uniform and ultrathin (5-50 nm) compact TiO2 films on
fluorine-doped tin oxide (FTO) glass substrates. The thickness of the film was
tuned by changing the TiCl4 precursor concentration. The formed TiO2 follows the
texture of the underlying FTO substrates, but at higher TiCl4 concentrations, the
surface roughness is substantially decreased. This change occurs at a film
thickness close to 20-30 nm. A similar TiCl4 concentration is needed to produce
crystalline TiO2 films. Furthermore, below this film thickness, the underlying
FTO might be exposed resulting in pinholes in the compact TiO2 layer. When
integrated into mesoscopic perovskite solar cells there appears to be a similar
critical compact TiO2 layer thickness above which the devices perform more
optimally. The power conversion efficiency was improved by more than 50% (from
5.5% to ~8.6%) when inserting a compact TiO2 layer. Devices without or with very
thin compact TiO2 layers display J-V curves with an "s-shaped" feature in the
negative voltage range, which could be attributed to immobilized negative ions at
the electron-extracting interface. A strong correlation between the magnitude of
the s-shaped feature and the exposed FTO seen in the X-ray photoelectron
spectroscopy measurements indicates that the s-shape is related to pinholes in
the compact TiO2 layer when it is too thin.
PMID- 28488847
TI - A Superior Polymer Electrolyte with Rigid Cyclic Carbonate Backbone for
Rechargeable Lithium Ion Batteries.
AB - The fabricating process of well-known Bellcore poly(vinylidene fluoride
hexafluoropropylene) (PVdF-HFP)-based polymer electrolytes is very complicated,
tedious, and expensive owing to containing a large amount of fluorine
substituents. Herein, a novel kind of poly(vinylene carbonate) (PVCA)-based
polymer electrolyte is developed via a facile in situ polymerization method,
which possesses the merits of good interfacial compatibility with electrodes. In
addition, this polymer electrolyte presents a high ionic conductivity of 5.59 *
10-4 S cm-1 and a wide electrochemical stability window exceeding 4.8 V vs Li+/Li
at ambient temperature. In addition, the rigid cyclic carbonate backbone of
poly(vinylene carbonate) endows polymer electrolyte a superior mechanical
property. The LiFe0.2Mn0.8PO4/graphite lithium ion batteries using this polymer
electrolyte deliver good rate capability and excellent cyclability at room
temperature. The superior performance demonstrates that the PVCA-based
electrolyte via in situ polymerization is a potential alternative polymer
electrolyte for high-performance rechargeable lithium ion batteries.
PMID- 28488848
TI - Directionally Interacting Spheres and Rods Form Ordered Phases.
AB - The structures formed by mixtures of dissimilarly shaped nanoscale objects can
significantly enhance our ability to produce nanoscale architectures. However,
understanding their formation is a complex problem due to the interplay of
geometric effects (entropy) and energetic interactions at the nanoscale. Spheres
and rods are perhaps the most basic geometrical shapes and serve as convenient
models of such dissimilar objects. The ordered phases formed by each of these
individual shapes have already been explored, however, when mixed, spheres and
rods have demonstrated only limited structural organization to date. Here, we
show using experiments and theory that the introduction of directional
attractions between rod ends and isotropically interacting spherical
nanoparticles (NPs) through DNA base pairing leads to the formation of ordered
three-dimensional lattices. The spheres and rods arrange themselves in a complex
alternating manner, where the spheres can form either a face-centered cubic (FCC)
or hexagonal close-packed (HCP) lattice, or a disordered phase, as observed by in
situ X-ray scattering. Increasing NP diameter at fixed rod length yields an
initial transition from a disordered phase to the HCP crystal, energetically
stabilized by rod-rod attraction across alternating crystal layers, as revealed
by theory. In the limit of large NPs, the FCC structure is instead stabilized
over the HCP by rod entropy. We, therefore, propose that directionally specific
attractions in mixtures of anisotropic and isotropic objects offer insight into
unexplored self-assembly behavior of noncomplementary shaped particles.
PMID- 28488850
TI - Fabrication of Polyimide Membrane Incorporated with Functional Graphene Oxide for
CO2 Separation: The Effects of GO Surface Modification on Membrane Performance.
AB - Two kinds of isocyanate were used to modify graphene oxide (GO) samples. Then,
polyimide (PI) hybrid membranes containing GO and modified GO were prepared by in
situ polymerization. The permeation of CO2 and N2 was studied using these novel
membranes. The morphology experiments showed that the isocyanate groups were
successfully grafted on the surface of GO by replacement of the oxygen-containing
functional groups. After modification, the surface polarity of the GO increased,
and more defect structures were introduced into the GO surface. This resulted in
a good distribution of more modified GO samples in the PI polymer matrix. Thus,
the PI hybrid membranes incorporated by modified GO samples showed a high gas
permeability and ideal selectivity of membranes. In addition, enhancement of the
selectivity due to the solubility of CO2 played a major role in the increase in
the separation performance of the hybrid membranes for CO2, although the
diffusion coefficients for CO2 also increased. Both the higher condensability and
the strong affinity between CO2 molecules and GO in the polymer matrix caused an
enhancement of the solubility selectivity higher than the diffusion selectivity
after GO surface modification.
PMID- 28488851
TI - Simultaneous Surface-Enhanced Raman Spectroscopy Detection of Multiplexed
MicroRNA Biomarkers.
AB - Simultaneous detection of cancer biomarkers holds great promise for the early
diagnosis of cancer. In the present work, an ultrasensitive and reliable surface
enhanced Raman scattering (SERS) sensor has been developed for simultaneous
detection of multiple liver cancer related microRNA (miRNA) biomarkers. We first
proposed a novel strategy for the synthesis of nanogap-based SERS nanotags by
modifying gold nanoparticles (AuNPs) with thiolated DNA and nonfluorescent small
encoding molecules. We also explored a simple approach to a green synthesis of
hollow silver microspheres (Ag-HMSs) with bacteria as templates. On the basis of
the sandwich hybridization assay, probe DNA-conjugated SERS nanotags used as SERS
nanoprobes and capture DNA-conjugated Ag-HMSs used as capture substrates were
developed for the detection of target miRNA with a detection limit of 10 fM.
Multiplexing capability for simultaneous detection of the three liver cancer
related miRNAs with the high sensitivity and specificity was demonstrated using
the proposed SERS sensor. Furthermore, the practicability of the SERS sensor was
supported by the successful determination of target miRNA in cancer cells. The
experimental results indicated that the proposed strategy holds significant
potential for multiplex detection of cancer biomarkers and offers the opportunity
for future applications in clinical diagnosis.
PMID- 28488849
TI - Solution Conformations and Dynamics of Substrate-Bound Cytochrome P450 MycG.
AB - MycG is a P450 monooxygenase that catalyzes the sequential hydroxylation and
epoxidation of mycinamicin IV (M-IV), the last two steps in the biosynthesis of
mycinamicin II, a macrolide antibiotic isolated from Micromonospora griseorubida.
The crystal structure of MycG with M-IV bound was previously determined but
showed the bound substrate in an orientation that did not rationalize the
observed regiochemistry of M-IV hydroxylation. Nuclear magnetic resonance
paramagnetic relaxation enhancements provided evidence of an orientation of M-IV
in the MycG active site more compatible with the observed chemistry, but
substrate-induced changes in the enzyme structure were not characterized. We now
describe the use of amide 1H-15N residual dipolar couplings as experimental
restraints in solvated "soft annealing" molecular dynamics simulations to
generate solution structural ensembles of M-IV-bound MycG. Chemical shift
perturbations, hydrogen-deuterium exchange, and 15N relaxation behavior provide
insight into the dynamic and electronic perturbations in the MycG structure in
response to M-IV binding. The solution and crystallographic structures are
compared, and the possibility that the crystallographic orientation of bound M-IV
represents an inhibitory mode is discussed.
PMID- 28488852
TI - Structure and Dynamics of the Tetra-A Loop and (A-A)-U Sequence Motif within the
Coliphage GA Replicase RNA Operator.
AB - The three-dimensional structure of a RNA hairpin containing the RNA operator
binding site for bacteriophage GA coat protein is presented. The phage GA
operator contains the asymmetric (A-A)-U sequence motif and is capped by a four
adenine (tetra-A) loop. The uridine of the (A-A)-U motif preferentially pairs
with the 5'-proximal cross-strand adenine, and the 3'-proximal adenine stacks
into the helix. The tetra-A loop is well-ordered with adenine residues 2-4
forming a 3' stack. This loop conformation stands in contrast to the structure of
the 5'-AUUA loop of the related phage MS2 operator in which residues 1 and 2 form
a 5' stack. The context dependence of the (A-A)-U sequence motif conformation was
examined using structures of 76 unique occurrences from the Protein Data Bank.
The motif almost always has one adenine bulged and the other adenine adopting an
A-U base pair. In the case in which the (A-A)-U motif is flanked by only one
Watson-Crick base pair, the adenine adjacent to the flanking base pair tends to
bulge; 80% of motifs with a 3' flanking pair have a 3' bulged adenine, and 84% of
motifs with a 5' flanking pair have a 5' bulged adenine. The frequencies of 3'-
and 5'-proximal adenines bulging are 33 and 67%, respectively, when the (A-A)-U
motif is flanked by base pairs on both sides. Although a 3' flanking cytidine
correlates (88%) with bulging of the 5'-proximal adenine, no strict dependence on
flanking nucleotide identity was identified for the 5' side.
PMID- 28488853
TI - Metal-Organic Framework Template Synthesis of NiCo2S4@C Encapsulated in Hollow
Nitrogen-Doped Carbon Cubes with Enhanced Electrochemical Performance for Lithium
Storage.
AB - Owing to its richer redox reaction and remarkable electrical conductivity,
bimetallic nickel cobalt sulfide (NiCo2S4) is considered as an advanced electrode
material for energy-storage applications. Herein, nanosized NiCo2S4@C
encapsulated in a hollow nitrogen-doped carbon cube (NiCo2S4@D-NC) has been
fabricated using a core@shell Ni3[Co(CN)6]2@polydopamine (PDA) nanocube as the
precursor. In this composite, the NiCo2S4 nanoparticles coated with conformal
carbon layers are homogeneously embedded in a 3D high-conduction carbon shell
from PDA. Both the inner and the outer carbon coatings are helpful in increasing
the electrical conductivity of the electrode materials and prohibit the
polysulfide intermediates from dissolving in the electrolyte. When researched as
electrode materials for lithium storage, owing to the unique structure with
double layers of nitrogen-doped carbon coating, the as-obtained NiCo2S4@D-NC
electrode maintains an excellent specific capacity of 480 mAh g-1 at 100 mA g-1
after 100 cycles. Even after 500 cycles at 500 mA g-1, a reversible capacity of
427 mAh g-1 can be achieved, suggesting an excellent rate capability and an
ultralong cycling life. This remarkable lithium storage property indicates its
potential application for future lithium-ion batteries.
PMID- 28488854
TI - Long-Life Lithium-Sulfur Battery Derived from Nori-Based Nitrogen and Oxygen Dual
Doped 3D Hierarchical Biochar.
AB - Due to restrictions on the low conductivity of sulfur and soluble polysulfides
during discharge, lithium sulfur batteries are unsuitable for further large scale
applications. The current carbon based cathodes suffer from poor cycle stability
and high cost. Recently, heteroatom doped carbons have been considered as a
settlement to enhance the performance of lithium sulfur batteries. With this
strategy, we report the low cost activated nori based N,O-doped 3D hierarchical
carbon material (ANC) as a sulfur host. The N,O dual-doped ANC reveals an
elevated electrochemical performance, which exhibits not only a good rate
performance over 5 C, but also a high sulfur content of 81.2%. Further
importantly, the ANC represents an excellent cycling stability, the cathode
reserves a capacity of 618 mAh/g at 2 C after 1000 cycles, which shows a 0.022%
capacity decay per cycle.
PMID- 28488855
TI - Filtration and Electrochemical Disinfection Performance of PAN/PANI/AgNWs-CC
Composite Nanofiber Membrane.
AB - The removal and inactivation of waterborne pathogens from drinking water are
important for human health. Here, a polyacrylonitrile/polyaniline/silver
nanowires-carbon fiber cloth (PAN/PANI/AgNWs-CC) composite nanofiber membrane was
fabricated using a simple and rapid coelectrospinning process, and an electrical
device was applied with the PAN/PANI/AgNWs-CC filter for water electrochemical
disinfection. The effects of voltage, flow rate, and microbial concentration on
the filtration and electrochemical disinfection performance of the nanocomposite
membrane were investigated. The characterization results show that PAN/PANI/AgNWs
with uniform diameters and without beads were successfully fabricated on CC.
AgNWs were uniformly distributed in the PAN/PANI/AgNWs. The PAN/PANI/AgNWs-CC
filter was an effective sieve for completely removing both Escherichia coli and
Staphylococcus aureus in the absence of applied voltage, and the sieved bacteria
were completely inactivated by the released silver within 8 h. Over 99.999%
inactivation of the sieved bacteria was achieved within a few seconds by
concurrent filtration and electrochemical disinfection under a voltage of 3 V.
This high performance is enabled by means of an electrical mechanism, and an
extremely high electric field induces sharp AgNWs tips to generate electroporated
pores in the bacteria. The electrochemical PAN/PANI/AgNWs-CC membrane is an
excellent material with potential application value in point-of-use drinking
water treatment.
PMID- 28488856
TI - Light-Driven Hydrogen Generation from Microemulsions Using Metallosurfactant
Catalysts and Oxalic Acid.
AB - A unique microemulsion-based photocatalytic water reduction system is
demonstrated. Iridium- and rhodium-based metallosurfactants, namely,
[Ir(ppy)2(dhpdbpy)]Cl and [Rh(dhpdbpy)2Cl2]Cl (where ppy = 2-phenylpyridine and
dhpdbpy = 4,4'-diheptadecyl-2,2'-bipyridine), were employed as photosensitizer
and proton reducing catalyst, respectively, along with oxalic acid as a
sacrificial reductant in a toluene/water biphasic mixture. The addition of 1
octylamine is proposed to initiate the reaction, by coupling with oxalic acid to
form an ion pair, which acts as an additional surfactant. Concentration
optimizations yielded high activity for both the photosensitizer (240 turnovers,
turnover frequency (TOF) = 200 h-1) and catalyst (400 turnovers, TOF = 230 h-1),
with the system generating hydrogen even after 95 h. Mechanistic insights were
provided by gas-phase Raman, electrochemical, and luminescence quenching
analysis, suggesting oxidative quenching to be the principle reaction pathway.
PMID- 28488857
TI - A Regioselective Synthesis of 6-Alkyl- and 6-Aryluracils by Cs2CO3- or K3PO4
Promoted Dimerization of 3-Alkyl- and 3-Aryl-2-Propynamides.
AB - A regioselective synthesis of 6-alkyl- and 6-aryluracils was developed by the
dimerization of 3-alkyl- and 3-aryl-2-propynamides promoted by either Cs2CO3 or
K3PO4. A range of 3-aryl-2-propynamides, with both electron-deficient and
electron-rich 3-aryl substituents, were successfully reacted in high yields. Cs+
acts as a soft Lewis acid to polarize the carbon-carbon triple bond, and solid
K3PO4 interacts with carbonyl oxygen, promoting intermolecular nucleophilic
attack by the only weakly nucleophilic amide nitrogen. Experiments were conducted
to support the proposed mechanism.
PMID- 28488858
TI - Development of a High-Throughput Ion-Exchange Resin Characterization Workflow.
AB - A novel high-throughout (HTR) ion-exchange (IEX) resin workflow has been
developed for characterizing ion exchange equilibrium of commercial and
experimental IEX resins against a range of different applications where water
environment differs from site to site. Because of its much higher throughput,
design of experiment (DOE) methodology can be easily applied for studying the
effects of multiple factors on resin performance. Two case studies will be
presented to illustrate the efficacy of the combined HTR workflow and DOE method.
In case study one, a series of anion exchange resins have been screened for
selective removal of NO3- and NO2- in water environments consisting of multiple
other anions, varied pH, and ionic strength. The response surface model (RSM) is
developed to statistically correlate the resin performance with the water
composition and predict the best resin candidate. In case study two, the same HTR
workflow and DOE method have been applied for screening different cation exchange
resins in terms of the selective removal of Mg2+, Ca2+, and Ba2+ from high total
dissolved salt (TDS) water. A master DOE model including all of the cation
exchange resins is created to predict divalent cation removal by different IEX
resins under specific conditions, from which the best resin candidates can be
identified. The successful adoption of HTR workflow and DOE method for studying
the ion exchange of IEX resins can significantly reduce the resources and time to
address industry and application needs.
PMID- 28488859
TI - Enhanced Cytotoxicity and Reactivity of a Novel Platinum(IV) Family with DNA
Targeting Naphthalimide Ligands.
AB - Pt(IV) complexes are known as prodrugs that can potentially overcome cisplatin
limitations by slowing down its reactivity and, once reduced, act as the
corresponding Pt(II) drugs. We report a new approach toward trans Pt(IV)
complexes, conceived to afford nonconventional active trans Pt(II) complexes with
dual-targeting properties. The reduction of the complexes has been studied in the
presence of ascorbic acid and glutathione, showing that different species are
formed in the process. The interaction with DNA after reduction has been also
studied and correlated to the formation of Pt(II) species. The cytotoxicity
profile of the Pt(IV) complexes corroborated the rationale behind this approach.
PMID- 28488860
TI - Flexible and Highly Photosensitive Electrolyte-Gated Organic Transistors with
Ionogel/Silver Nanowire Membranes.
AB - Flexible and low-voltage photosensors with high near-infrared (NIR) sensitivity
are critical for realization of interacting humans with robots and environments
by thermal imaging or night vision techniques. In this work, we for the first
time develop an easy and cost-effective process to fabricate flexible and
ultrathin electrolyte-gated organic phototransistors (EGOPTs) with high
transparent nanocomposite membranes of high-conductivity silver nanowire (AgNW)
networks and large-capacitance iontronic films. A high responsivity of 1.5 * 103
A.W1-, high sensitivity of 7.5 * 105, and 3 dB bandwidth of ~100 Hz can be
achieved at very low operational voltages. Experimental studies in temporal
photoresponse characteristics reveal the device has a shorter photoresponse time
at lower light intensity since strong interactions between photoexcited hole
carriers and anions induce extra long-lived trap states. The devices, benefiting
from fast and air-stable operations, provide the possibility of the organic
photosensors for constructing cost-effective and smart optoelectronic systems in
the future.
PMID- 28488861
TI - Engineering Pt/Pd Interfacial Electronic Structures for Highly Efficient Hydrogen
Evolution and Alcohol Oxidation.
AB - Tailoring the interfacial structure of Pt-based catalysts has emerged as an
effective strategy to improve catalytic activity. However, little attention has
been focused on investigating the relationship between the interfacial facets and
their catalytic activity. Here, we design and implement Pd-Pt interfaces with
controlled heterostructure features by epitaxially growing Pt nanoparticles on Pd
nanosheets. On the basis of both density functional theory calculation and
experimental results, we demonstrate that charge transfer from Pd to Pt is highly
dependent on the interfacial facets of Pd substrates. Therefore, the Pd-Pt
heterostructure with Pd(100)-Pt interface exhibits excellent activity and long
term stability for hydrogen evolution and methanol/ethanol oxidation reactions in
alkaline medium, much better than that with Pd (111)-Pt interface or commercial
Pt/C. Interfacial crystal facet-dependent electronic structural modulation sheds
a light on the design and investigation of new heterostructures for high-activity
catalysts.
PMID- 28488862
TI - Gardenifolins A-H, Scalemic Neolignans from Gardenia ternifolia: Chiral
Resolution, Configurational Assignment, and Cytotoxic Activities against the HeLa
Cancer Cell Line.
AB - From the tropical plant Gardenia ternifolia Schumach. and Thonn. (Rubiaceae),
eight stereoisomeric 2,3-dihydrobenzo[b]furan neolignans, named gardenifolins A-H
(1a-d and 2a-d), were isolated and fully structurally characterized. Reversed
phase chromatography of a stem bark extract afforded two peaks, viz. mixtures I
and II, each one consisting of two diastereomers and their respective
enantiomers. They were resolved and stereochemically analyzed by HPLC on a chiral
phase coupled to electronic circular dichroism (ECD) spectroscopy, giving single
ECD spectra of all eight stereoisomers. The double-bond geometries (E or Z) of
the gardenifolins A-H and their relative configurations (cis or trans) at the
stereogenic centers C-7 and C-8 in the dihydrofuran ring system were assigned by
1D and 2D NMR methods, in particular, using NOE difference experiments, whereas
the absolute configurations of the isolated enantiomers were established by ECD
spectroscopy by applying the reversed helicity rule. The individual pure
gardenifolin isomers A-H showed the most different cytotoxic effects against the
human cancer HeLa cell line, with 1d and 2a displaying the highest activities,
with IC50 values of 21.0 and 32.5 MUM, respectively. Morphological experiments
indicated that gardenifolin D (1d) induces apoptosis of HeLa cells at 25 MUM.
PMID- 28488863
TI - V67L Mutation Fills an Internal Cavity To Stabilize RecA Mtu Intein.
AB - Inteins mediate protein splicing, which has found extensive applications in
protein science and biotechnology. In the Mycobacterium tuberculosis RecA mini
mini intein (DeltaDeltaIhh), a single valine to leucine substitution at position
67 (V67L) dramatically increases intein stability and activity. However, crystal
structures show that the V67L mutation causes minimal structural rearrangements,
with a root-mean-square deviation of 0.2 A between DeltaDeltaIhh-V67 and
DeltaDeltaIhh-L67. Thus, the structural mechanisms for V67L stabilization and
activation remain poorly understood. In this study, we used intrinsic tryptophan
fluorescence, high-pressure nuclear magnetic resonance (NMR), and molecular
dynamics (MD) simulations to probe the structural basis of V67L stabilization of
the intein fold. Guanidine hydrochloride denaturation monitored by fluorescence
yielded free energy changes (DeltaGf degrees ) of -4.4 and -6.9 kcal mol-1 for
DeltaDeltaIhh-V67 and DeltaDeltaIhh-L67, respectively. High-pressure NMR showed
that DeltaDeltaIhh-L67 is more resistant to pressure-induced unfolding than
DeltaDeltaIhh-V67 is. The change in the volume of folding (DeltaVf) was
significantly larger for V67 (71 +/- 2 mL mol-1) than for L67 (58 +/- 3 mL mol-1)
inteins. The measured difference in DeltaVf (13 +/- 3 mL mol-1) roughly
corresponds to the volume of the additional methylene group for Leu, supporting
the notion that the V67L mutation fills a nearby cavity to enhance intein
stability. In addition, we performed MD simulations to show that V67L decreases
side chain dynamics and conformational entropy at the active site. It is
plausible that changes in cavities in V67L can also mediate allosteric effects to
change active site dynamics and enhance intein activity.
PMID- 28488864
TI - Temperature and Pressure Dependences of the Reactions of Fe+ with Methyl Halides
CH3X (X = Cl, Br, I): Experiments and Kinetic Modeling Results.
AB - The pressure and temperature dependences of the reactions of Fe+ with methyl
halides CH3X (X = Cl, Br, I) in He were measured in a selected ion flow tube over
the ranges 0.4 to 1.2 Torr and 300-600 K. FeX+ was observed for all three halides
and FeCH3+ was observed for the CH3I reaction. FeCH3X+ adducts (for all X) were
detected in all reactions. The results were interpreted assuming two-state
reactivity with spin-inversions between sextet and quartet potentials. Kinetic
modeling allowed for a quantitative representation of the experiments and for
extrapolation to conditions outside the experimentally accessible range. The
modeling required quantum-chemical calculations of molecular parameters and
detailed accounting of angular momentum effects. The results show that the FeX+
products come via an insertion mechanism, while the FeCH3+ can be produced from
either insertion or SN2 mechanisms, but the latter we conclude is unlikely at
thermal energies. A statistical modeling cannot reproduce the competition between
the bimolecular pathways in the CH3I reaction, indicating that some more direct
process must be important.
PMID- 28488865
TI - Correlations in the Solute-Solvent Dynamics Reach Beyond the First Hydration
Shell of Ions.
AB - While the real-space structure of solvation shells has been explored for decades,
a dynamical perspective that directly relies on changes in the H-bond network
became accessible more recently mainly via far-infrared (THz) spectroscopies. A
remaining key question is how many hydration shells are affected by ion-induced
network perturbations. We disclose that theoretical THz difference spectra of
aqueous salt solutions can be deciphered in terms of only a handful of dipolar
auto- and cross-correlations, including the second solvation shell. This
emphasizes the importance of cross-correlations being often neglected in
multicomponent models. Analogously, experimental THz responses of simple ions can
be deciphered in a similar way. Dramatic intensity cancellations due to large
positive and negative contributions are found to effectively shift intensity
maxima. Thus, THz spectroscopy provides an unprecedented view on the details of
hydration dynamics, which can be understood by a combination of experiment and
theory.
PMID- 28488866
TI - Mechanism, Regio-, and Diastereoselectivity of Rh(III)-Catalyzed Cyclization
Reactions of N-Arylnitrones with Alkynes: A Density Functional Theory Study.
AB - Nitrones have been used for rhodium-catalyzed cyclization C-H bond activation and
O atom transfer of arylnitrones with alkynes by Chang et al. ( J. Am. Chem. Soc.
2015 , 137 , 4908 - 4911 ). Density functional theory method has been used to
study the mechanism, regio-, and diastereoselectivity of type reactions. The
results elucidated that the reaction pathway for Rh(III)-catalyzed cyclization of
N-arylnitrones with alkyne contains a C-H bond activation, an alkyne insertion
into Rh-C bond, a reductive elimination to form a Rh(I) complex, an oxidative
addition leading to N-O cleavage, an imine insertion into the Rh-C bond, and the
final protonolysis to regenerate the products and the active catalyst. The
regioselectivity of this reaction with asymmetric alkyne is controlled by the
electronic effect in alkyne insertion type instead of steric effects. The
distortion-interaction analysis is also used to explain the regioselectivity. The
diastereoselectivity is controlled by the imine insertion step. In this step, the
sterically less hindered transition state is favored, leading to stereoselective
product formation.
PMID- 28488867
TI - Experimental and Theoretical Investigation of the Structural Role of Titanium
Oxide in CaO-P2O5-TiO2 Invert Glass.
AB - Understanding the structural role of TiO2 in calcium phosphate invert glasses is
key for developing a new glass design for biomedical applications. Experimental
and computational analysis methods were used to investigate the impact of TiO2
substitution in these glasses. Spectroscopic analyses indicated that titanium
oxide exists as both TiO4 and TiO6 units, leading to the formation of Ti-O-P
bonds, in spite of depolymerization of the phosphate chains. Classical molecular
dynamics showed that the presence of TiO2 influences the phosphate units and CaO
polyhedral structures. The formation of the Ti-O-P bonds caused an increase in
the network connectivity of the invert glasses, leading to the improvement of the
glass forming ability and wettability. The addition of TiO2 to calcium phosphate
invert glasses led to the introduction of bioactivity.
PMID- 28488868
TI - Long-Range Lattice Engineering of MoTe2 by a 2D Electride.
AB - Doping two-dimensional (2D) semiconductors beyond their degenerate levels
provides the opportunity to investigate extreme carrier density-driven
superconductivity and phase transition in 2D systems. Chemical functionalization
and the ionic gating have achieved the high doping density, but their effective
ranges have been limited to ~1 nm, which restricts the use of highly doped 2D
semiconductors. Here, we report on electron diffusion from the 2D electride
[Ca2N]+.e- to MoTe2 over a distance of 100 nm from the contact interface,
generating an electron doping density higher than 1.6 * 1014 cm-2 and a lattice
symmetry change of MoTe2 as a consequence of the extreme doping. The long-range
lattice symmetry change, suggesting a length scale surpassing the depletion width
of conventional metal-semiconductor junctions, was a consequence of the low work
function (2.6 eV) with highly mobile anionic electron layers of [Ca2N]+.e-. The
combination of 2D electrides and layered materials yields a novel material design
in terms of doping and lattice engineering.
PMID- 28488869
TI - Insights into the Correlation of Aluminum Distribution and Bronsted Acidity in H
Beta Zeolites from Solid-State NMR Spectroscopy and DFT Calculations.
AB - Here we utilized 27Al MAS/MQMAS and 31P MAS NMR of quantitative adsorption of
trimethylphosphine oxide (TMPO) and DFT calculations to elucidate the
relationship between Al distribution and Bronsted acidity of series H-Beta
zeolites derived from dealumination of Al-rich H-Beta zeolite. Three types of
Bronsted acid strengths corresponding to different specific Al T-sites were
demonstrated. The removal of one framework Al in 5MR2--2Al and 6MR-2Al sites led
to increasing the Bronsted acid strength of dealuminated H-Beta. Our findings on
such exact correlation between specific Al distributions and corresponding
Bronsted acid sites may guide the controlling Al distribution to get desired acid
properties through zeolite synthesis or finely tuned dealumination, which has a
great impact on the catalytic activity and selectivity of zeolite catalysts.
PMID- 28488870
TI - Strong van der Waals Adhesion of a Polymer Film on Rough Substrates.
AB - We propose that chemically inert polymeric films can enhance van der Waals (vdW)
forces in the same way as nanofabrication of biomimetic adhesive materials. For
the vdW adhesion of an ethylene-chlorotrifluoroethylene (ECTFE) film on rough
metal and dielectric substrates, we present a model that combines microscopic
quantum-chemistry simulations of the polymer response functions and the
equilibrium monomer-substrate distance with a macroscopic quantum-electrodynamics
calculation of the Casimir force between the polymer film and the substrate. We
predict adhesive forces up to 2.22 kN/mm2, where the effect is reduced by
substrate roughness and for dielectric surfaces.
PMID- 28488871
TI - Spatial Targeting of Tumor-Associated Macrophages and Tumor Cells with a pH
Sensitive Cluster Nanocarrier for Cancer Chemoimmunotherapy.
AB - Chemoimmunotherapy, which combines chemotherapeutics with immune-modulating
agents, represents an appealing approach for improving cancer therapy. To
optimize its therapeutic efficacy, differentially delivering multiple therapeutic
drugs to target cells is desirable. Here we developed an immunostimulatory
nanocarrier (denoted as BLZ-945SCNs/Pt) that could spatially target tumor
associated macrophages (TAMs) and tumor cells for cancer chemoimmunotherapy. BLZ
945SCNs/Pt undergo supersensitive structure collapse in the prevascular regions
of tumor tissues and enable the simultaneous release of platinum (Pt)-prodrug
conjugated small particles and BLZ-945, a small molecule inhibitor of colony
stimulating factor 1 receptor (CSF-1R) of TAMs. The released BLZ-945 can be
preferentially taken up by TAMs to cause TAMs depletion from tumor tissues, while
the small particles carrying Pt-prodrug enable deep tumor penetration as well as
intracellularly specific drug release to kill more cancer cells. Our studies
demonstrate that BLZ-945SCNs/Pt outperform their monotherapy counterparts in
multiple tumor models. The underlying mechanism studies suggest that the designer
pH-sensitive codelivery nanocarrier not only induces apoptosis of tumor cells but
also modulates the tumor immune environment to eventually augment the antitumor
effect of CD8+ cytotoxic T cells through TAMs depletion.
PMID- 28488872
TI - Luminescent Organic Semiconducting Langmuir Monolayers.
AB - In recent years, monolayer organic field-effect devices such as transistors and
sensors have demonstrated their high potential. In contrast, monolayer
electroluminescent organic field-effect devices are still in their infancy. One
of the key challenges here is to create an organic material that self-organizes
in a monolayer and combines efficient charge transport with luminescence. Herein,
we report a novel organosilicon derivative of oligothiophene-phenylene dimer D2
Und-PTTP-TMS (D2, tetramethyldisiloxane; Und, undecylenic spacer; P, 1,4
phenylene; T, 2,5-thiophene; TMS, trimethylsilyl) that meets these requirements.
The self-assembled Langmuir monolayers of the dimer were investigated by steady
state and time-resolved photoluminescence spectroscopy, atomic force microscopy,
X-ray reflectometry, and grazing-incidence X-ray diffraction, and their
semiconducting properties were evaluated in organic field-effect transistors. We
found that the best uniform, fully covered, highly ordered monolayers were
semiconducting. Thus, the ordered two-dimensional (2D) packing of conjugated
organic molecules in the semiconducting Langmuir monolayer is compatible with its
high-yield luminescence, so that 2D molecular aggregation per se does not
preclude highly luminescent properties. Our findings pave the way to the rational
design of functional materials for monolayer organic light-emitting transistors
and other optoelectronic devices.
PMID- 28488875
TI - Absolute and relative morbidity burdens attributable to various illnesses and
injuries, active component, U.S. Armed Forces, 2016.
PMID- 28488873
TI - Removal of Differential Capacitive Interferences in Fast-Scan Cyclic Voltammetry.
AB - Due to its high spatiotemporal resolution, fast-scan cyclic voltammetry (FSCV) at
carbon-fiber microelectrodes enables the localized in vivo monitoring of
subsecond fluctuations in electroactive neurotransmitter concentrations. In
practice, resolution of the analytical signal relies on digital background
subtraction for removal of the large current due to charging of the electrical
double layer as well as surface faradaic reactions. However, fluctuations in this
background current often occur with changes in the electrode state or ionic
environment, leading to nonspecific contributions to the FSCV data that confound
data analysis. Here, we both explore the origin of such shifts seen with local
changes in cations and develop a model to account for their shape. Further, we
describe a convolution-based method for removal of the differential capacitive
contributions to the FSCV current. The method relies on the use of a small
amplitude pulse made prior to the FSCV sweep that probes the impedance of the
system. To predict the nonfaradaic current response to the voltammetric sweep,
the step current response is differentiated to provide an estimate of the
system's impulse response function and is used to convolute the applied waveform.
The generated prediction is then subtracted from the observed current to the
voltammetric sweep, removing artifacts associated with electrode impedance
changes. The technique is demonstrated to remove select contributions from
capacitive characteristics changes of the electrode both in vitro (i.e., in flow
injection analysis) and in vivo (i.e., during a spreading depression event in an
anesthetized rat).
PMID- 28488874
TI - An Optically Modulated Self-Assembled Resonance Energy Transfer Pass Gate.
AB - We demonstrate an optically controlled molecular-scale pass gate that uses the
photoinduced dark states of fluorescent molecules to modulate the flow of
excitons. The device consists of four fluorophores spatially arranged on a self
assembled DNA nanostructure. Together, they form a resonance energy transfer
(RET) network resembling a standard transistor with a source, channel, drain, and
gate. When the gate fluorophore is directly excited, the device is toggled on.
Excitons flow freely from the source to the drain, producing strong output
fluorescence. Without this excitation, exciton flow through the device is
hindered by absorbing paths along the way, resulting in weak output fluorescence.
In this Letter, we describe the design and fabrication of the pass gate. We
perform a steady-state analysis revealing that the on/off fluorescence ratio for
this particular implementation is ~8.7. To demonstrate dynamic modulation of the
pass gate, we toggle the gate excitation on and off and measure the corresponding
change in output fluorescence. We characterize the rise and fall times of these
transitions, showing that they are faster and/or more easily achieved than other
methods of RET network modulation. The pass gate is the first dynamic RET-based
logic gate exclusively modulated by dark states and serves as a proof-of-concept
device for building more complex RET systems in the future.
PMID- 28488877
TI - Ambulatory visits, active component, U.S. Armed Forces, 2016.
PMID- 28488876
TI - Hospitalizations, active component, U.S. Armed Forces, 2016.
PMID- 28488878
TI - Surveillance snapshot: Illness and injury burdens, reserve component, U.S. Armed
Forces, 2016.
PMID- 28488879
TI - Surveillance snapshot: Illness and injury burdens, recruit trainees, active
component, U.S. Armed Forces, 2016.
PMID- 28488880
TI - Absolute and relative morbidity burdens attributable to various illnesses and
injuries, non-service member beneficiaries of the Military Health System, 2016.
PMID- 28488881
TI - Mindfulness-Based Relapse Prevention for Methadone Maintenance: A Feasibility
Trial.
AB - OBJECTIVES: As rates of opiate misuse rise in the United States, so do
significant associated health and financial consequences to afflicted
individuals, their families, and society at large. Methadone maintenance therapy
(MMT) is one evidence-based approach to treating opiate addiction, yet
supplemental psychosocial treatment to support this approach is lacking.
Mindfulness-based relapse prevention (MBRP) has shown to be efficacious in
various substance use populations, but has yet to be assessed with MMT clients.
DESIGN: The current mixed methods study was designed to inform protocol
adaptation for MMT clients and to evaluate the feasibility, acceptability, and
preliminary efficacy of MBRP for this population. SUBJECTS: The sample consisted
of adults (N = 15) recruited from a methadone clinic to participate in a 6-week
MBRP course. OUTCOME MEASURES: Data from focus groups and course satisfaction
surveys supported feasibility and acceptability of the intervention. Self-report
outcome measures included depression, anxiety, craving, symptoms of post
traumatic stress, and experiential avoidance, and were assessed at baseline and
postcourse. RESULTS: Mean scores on all primary outcomes changed in the expected
direction at postcourse, and baseline to postcourse changes in depression,
craving, and trauma symptoms reached statistical significance. CONCLUSIONS:
Results from this initial pilot trial support feasibility and acceptability, and
provide preliminary data on outcomes for future trials of mindfulness-based
approaches within the MMT community.
PMID- 28488882
TI - Development of bioanalytical assays for variegin, a peptide-based bivalent direct
thrombin inhibitor.
AB - AIM: Variegin is an anticoagulant peptide that will be tested in porcine models
of percutaneous coronary intervention. We developed three bioanalytical assays
for variegin quantitation and utilized these methods to evaluate pharmacokinetics
of variegin in pigs. Results & methodology: The LC-MS/MS, thrombin amidolytic and
modified thrombin time assays had a quantitation range of 21.6-5541.7, 10.8
5541.7 and 5.4-5541.7 nM in human plasma, respectively. The elimination half
lives obtained using the LC-MS/MS, modified thrombin time and thrombin amidolytic
assays were 52.3 +/- 4.4, 50.4 +/- 5.9 and 67.7 +/- 6.3 min, respectively.
CONCLUSION: We developed three bioanalytical assays for a novel direct thrombin
inhibitor, variegin. The thrombin time assay is optimized for variegin
quantitation during future porcine studies and clinical trials.
PMID- 28488883
TI - Ultrasensitive bioanalysis: current status and future trends.
AB - Ligand-binding techniques such as immunoassays, the reference for clinical
diagnosis, offer a wide range of innovative approaches based on signal DNA
amplification, nanotechnologies or digital assays, which result in technologies
with sensitivities more than 1000-times that of formats used 20 years ago.
Providing that these technologies gain acceptance and translate into robust
commercial platforms, we expect that several fields will be impacted in the near
future, including the clinical diagnosis of cancer markers, the early detection
of infectious diseases and the safety of biotherapeutics. Furthermore, the
combination of these techniques with microfluidic systems will allow probing of
biological diversity at the single cell level and will lead to the discovery of
novel and rare biomarkers.
PMID- 28488884
TI - Evaluation of a novel risk assessment method for self-harm associated with
Borderline Personality Disorder.
AB - OBJECTIVES: Borderline personality disorder (BPD) is associated with frequent
self-harm and suicidal behaviours. This study compared physician-assessed self
harm risk and intervention choice according to a (i) standard risk assessment and
(ii) BPD-specific risk assessment methods. METHODS: Forty-five junior and senior
mental health physicians were assigned to standard or BPD-specific risk training
groups. The assessment utilized a BPD case vignette containing four scenarios
describing high/low lethality self-harm and chronic/new patterns of self-harm
behaviour. Participants chose from among four interventions, each corresponding
to a risk category. RESULTS: Standard and BPD-specific groups were alike in their
assessment of self-harm risk. Divergence occurred on intervention choice for
assessments of low lethality, chronic risk ( p<.01) and high lethality, chronic
risk ( p<.005). Overall, psychiatrists were more likely than their junior
colleagues to correctly assess risk and management options. CONCLUSIONS: Although
standard and BPD-specific methods are well aligned for assessing self harm
associated risk, BPD-specific training raised awareness of BPD-appropriate
interventions, particularly in the context of chronic patterns of self-harm
behaviour. Wider dissemination of BPD-specific risk training may enhance the
confidence of mental health clinicians in identifying the nature of self-harm
risk as well as the most clinically appropriate interventions for clients with
BPD.
PMID- 28488885
TI - Respiratory muscle strength and pulmonary function in children with rhinitis and
asthma after a six-minute walk test.
AB - OBJECTIVE: Rhinitis and asthma decrease quality of life. Few studies have
assessed the performance of children with asthma or rhinitis under submaximal
exercise. We evaluated maximal respiratory pressures, spirometric parameters, and
ability to sustain submaximal exercise in these children before and after the 6
minute walk test (6MWT), compared to healthy children. METHODS: This cross
sectional, analytical study included 89 children aged 6-12 years in outpatient
follow-up: 27 healthy (H), 31 with rhinitis (R), and 31 with mild asthma under
control (A). Pulmonary function parameters and maximal respiratory pressures were
measured before and 5, 10, and 30 minutes after the 6MWT. Wilcoxon test was used
to compare numerical numerical variables between two groups and analysis of
variance or Kruskal-Wallis test for comparison among three groups. RESULTS: Total
distance traveled in the 6MWT was similar among the three groups. Compared to pre
test values, VEF1 (Forced Expiratory Volume in 1 second), VEF0.75 (Forced
Expiratory Volume in 0.75 second), and FEF25-75 (Forced Expiratory Flow 25-75% of
the Forced Vital Capacity - CVF - curve) decreased significantly after the 6MWT
in group A, and VEF0.75, FEF25-75, and VEF1/CVF decreased significantly in group
R. Groups A and R had lower Maximum Inspiratory Pressure values than group H
before and after the 6MWT at all time points assessed. CONCLUSIONS: The findings
suggest that children with rhinitis and mild asthma present with alterations in
respiratory muscle strength and pulmonary function not associated with clinical
complaints, reinforcing the concept of the united airways.
PMID- 28488886
TI - Network support, technology use, depression, and ART adherence among HIV-positive
MSM of color.
AB - Depression is associated with poor antiretroviral therapy (ART) adherence among
people living with HIV/AIDS. This relationship may be moderated by an
individual's social network characteristics. Our study sought to examine social
network correlates of treatment adherence among HIV-positive men recruited from
social service agencies throughout Los Angeles County (N = 150) to inform
technology-driven social support interventions for this population. We
administered egocentric social network and computer-assisted survey interviews
focused on demographic characteristics, health history, depressive symptoms, and
ART adherence, where adherence was assessed by the number of reasons participants
missed taking their medication, if ever. Significant univariate correlates of
adherence were included in a multivariable regression analysis, where the
moderating effect of having a network member who reminds participants to take
their HIV medication on the relationship between depression and adherence was
tested. Over 60% of participants reported clinically significant depressive
symptoms; this was significantly associated with lower adherence among those
without someone in their social network to remind them about taking their HIV
medication, even after adjusting for covariates in an ordinary least squares
regression (adjusted mean difference b = -1.61, SE = 0.42, p = 0.0003). Having a
network member who reminds participants to take their ART medication
significantly ameliorated the negative association between depression and
treatment adherence, especially for those reporting greater depressive symptoms
(p = 0.0394). Additionally, participants demonstrated high rates of technology
use to communicate with social network members. In order to achieve the aims of
the National HIV/AIDS Strategy, innovative interventions addressing mental health
to improve ART adherence are needed. Network strategies that leverage technology
may be helpful for improving ART adherence among HIV-positive men with comorbid
depressive symptoms.
PMID- 28488887
TI - Rapid and affordable genome-wide bisulfite DNA sequencing by XmaI-reduced
representation bisulfite sequencing.
AB - AIM: To develop a reduced representation bisulfite sequencing (RRBS) approach for
rapid and affordable genome-wide DNA methylation analysis. METHODS: We have
selected restriction endonuclease XmaI to produce RRBS library fragments. After
digestion and partial fill-in DNA fragments were ligated to barcoded adapters,
bisulfite converted, size-selected, and sequenced on the Ion Torrent Personal
Genome Machine. XmaI-RRBS results were compared with the previously published
RRBS data. RESULTS: We have developed an XmaI-RRBS method for rapid and
affordable genome-wide DNA methylation analysis, with library preparation taking
only 4 days and sequencing possible within 4 h. We have also addressed several
challenges in order to further improve the RRBS technology. XmaI-RRBS may be
performed on degraded DNA samples and is compatible with the bench-top next
generation sequencing machines.
PMID- 28488888
TI - Reply to: Uric Acid and Contrast-Induced Nephropathy: Diagnostic Marker,
Therapeutic Target, or Innocent Bystander?
PMID- 28488889
TI - Experiencing place: Younger people with dementia facing aged care.
AB - OBJECTIVES: There are currently few facilities for people with younger onset
dementia and they are placed by default into dementia care facilities designed
for the elderly. There is limited understanding of how people with younger onset
dementia and their care givers anticipate or experience aged residential care.
This qualitative study has used semi-structured interviews to give voice to the
opinions and perspectives of nine people with younger onset dementia and 11 care
givers. METHOD: Interpretative Phenomenological Analysis was used for idiographic
analysis, allowing examination of the lived experience of younger people with
dementia and an iterative exploration of what their experiences mean. RESULTS:
Themes of memory, autonomy and therapy emerged from the data. There is a need for
a familiar memory of place in an intergenerational community and home-like
setting. The loss of autonomy and ensuing stagnation or even institutional
internment was much feared. Appropriate exercise and purposeful occupational
activities as well as emotional support were valued therapies but often lacking
for this group Conclusions: Emotional distress with the loss of a meaningful life
can result from the placement of younger people with dementia into old age
services. Development of age-appropriate services are required.
PMID- 28488890
TI - Exploring experiences of and attitudes towards mental illness and disclosure
amongst health care professionals: a qualitative study.
AB - BACKGROUND: The literature suggests that many health professionals hold
stigmatising attitudes towards those with mental illness and that this impacts on
patient care. Little attention has been given to how these attitudes affect
colleagues with a mental illness. Current research demonstrates that stigma and
discrimination are common in the UK workplace and impact on one's decision to
disclose mental illness. AIMS: This study aims to explore health professionals'
experiences of and attitudes towards mental illness and disclosure in the
workplace. METHODS: This qualitative study involved semi-structured interviews
with 24 health professionals employed by an NHS (National Health Service) trust.
13 of these worked in mental health, and 11 in other health fields. Interviews
were transcribed and thematic analysis was used to identify themes. RESULTS: Five
key themes were identified from the data: personal experiences and their effect
in changing attitudes; perceived stigmatising views of mental illness in other
staff members; hypothetical disclosure: factors affecting one's decision;
attitudes towards disclosure; support in the workplace after disclosure; and,
applying only to those working outside of the mental health field, mental illness
is not talked about. The results indicated that participants had a great deal of
experience with colleagues with a mental illness and that support in the
workplace for such illnesses is variable. Attitudes of participating health
professionals towards colleagues with a mental illness appeared to be positive,
however, they did report that other colleagues held negative attitudes. Deciding
to disclose a mental illness was a carefully thought out decision with a number
of advantages and disadvantages noted. In particular, it was found that health
professionals' fear stigma and discrimination from colleagues and that this would
dissuade participants from disclosing a mental illness. CONCLUSION: In many
respects, this research supports the findings in other workplaces. Such findings
need to be investigated further to identify the degree to which these experiences
and attitudes can be applied to other health professionals in other healthcare
settings to determine what intervention is necessary. Importantly, this study has
also indicated that the level of support available to NHS health professionals
with a mental illness is variable, suggesting the need to identify and replicate
positive practice.
PMID- 28488891
TI - Missed Initial Medical Visits: Predictors, Timing, and Implications for Retention
in HIV Care.
AB - HIV disproportionately affects racial/ethnic minorities and individuals living in
the southern United States, and missed clinic visits account for much of this
disparity. We sought to evaluate: (1) predictors of missed initial HIV medical
visits, (2) time to initial visit, and (3) the association between initial visit
attendance and retention in HIV care. Chart reviews were conducted for 200
consecutive HIV-infected patients (100 in Dallas, 100 in San Antonio) completing
case management (CM) intake. Of these, 52 (26%) missed their initial visit, with
22 (11%) never presenting for care. Mean age was 40 years, 85% were men, >70%
were of minority race/ethnicity, and 28% had a new HIV diagnosis. Unemployment
(OR [95% CI] = 2.33 [1.04-5.24], p = 0.04) and lower attendance of CM visits (OR
= 3.08 [1.43-6.66], p = 0.004) were associated with missing the initial medical
visit. A shorter time to visit completion was associated with CD4 <= 200 (HR 1.90
[1.25-2.88], p = 0.003), Dallas study site (HR = 1.48 [1.03-2.14], p = 0.04), and
recent hospitalization (HR = 2.18 [1.38-3.43], p < 0.001). Patients who did not
complete their initial medical visit within 90 days of intake were unlikely to
engage in care. Initial medical visit attendance was associated with higher
proportion of visits attended (p = 0.04) and fewer gaps in care (p = 0.01).
Missed medical visits were common among HIV patients initiating or reinitiating
care in Texas. Employment and CM involvement predicted initial medical visit
attendance, which was associated with retention in care. New, early engagement
strategies are needed to decrease missed visits and reduce HIV health
disparities.
PMID- 28488892
TI - Dcp1a and GW182 Induce Distinct Cellular Aggregates and Have Different Effects on
microRNA Pathway.
AB - P-bodies are cytoplasmic foci composed of mRNAs and enzymes involved in mRNA
degradation. P-bodies have been found to link to RNA interference and RNA decay
mediated by microRNAs (miRNAs) and translational repression. Here, we aim to
investigate different effects of overexpressed Dcp1a or GW182 on cytoplasmic
aggregates formation and influence on miRNA pathway. Small RNAs were recruited
into endogenous foci of P-bodies and aggregates formed by Dcpa1 and GW182
overexpression. However, only overexpressed Dcp1a but not GW182 was colocalized
with DDX6, another component of P-bodies and suppressed protein translation. In
addition, we investigated the relationship between stress granules and miRNA
pathway and found that granules induced by G3BP1 overexpression could recruit
small RNAs into the granules and repressed protein translation. As Ago2 is a key
component of RNA-induced silencing complex, we also investigated the localization
of endogenous Ago2 (edo-Ago2) after Dcp1a and GW182 overexpression, and found
that endo-Ago2 did not colocalize with the aggregates induced by overexpression
of Dcpla, GW182, and G3BP1. Notably, the ability of miRNA to regulate its target
was enhanced by the granules induced by Dcp1a and G3BP1 expression. Our results
suggest that overexpressed Dcp1a and GW182 can form different cytoplasmic
aggregates and play distinct biological roles in the miRNA pathway.
PMID- 28488893
TI - VDR, RANKL and OPG polymorphisms as possible predisposing cofactors of
postmenopausal osteoporosis: explorative study in Italian population.
AB - Postmenopausal osteoporosis (PO) has a strong genetic component. Presently, the
published evidence on the association between the main single-nucleotide
polymorphisms (SNPs) of the receptor activator of nuclear factor-kb ligand
(RANKL), osteoprotegerin (OPG) and vitamin D receptor (VDR) and bone mass density
(BMD) are scarce, mostly considering Italian population. This study sought to
determine whether OPG (rs2073618), RANKL (rs9525641) and the VDR (rs2228570) SNPs
were associated with BMD in a sample of 139 North-Italian postmenopausal women.
The allelic distribution of rs9525641 in women with PO or osteopenia (OP + OPE
group) differed from controls (p < 0.05), suggesting that this allele might
confer a greater susceptibility to bone resorption. Concerning rs2228570, CC
genotype was associated with OP + OPE women, with a worst total hip BMD. Notably,
the combined genotype RANK (CT)-VDR (TT) was significantly associated to spine
BMD (p < 0.05). In conclusion, this pilot study showed that rs9525641 and
rs2228570 polymorphisms might contribute, separately or in combination, in
determining BMD phenotype in selected postmenopausal populations.
PMID- 28488894
TI - Development of a UHPLC-MS/MS (SRM) method for the quantitation of endogenous
glucagon and dosed GLP-1 from human plasma.
AB - AIM: The performance of glucagon and GLP-1 immunoassays is often poor, but few
sensitive LC-MS/MS methods exist as alternatives. EXPERIMENTAL: A multiplexed LC
MS/MS method using a 2D extraction technique was developed. RESULTS: The method
was established for the quantitation of endogenous glucagon (LLOQ: 15 pg/ml) and
dosed GLP-1 (LLOQ: 25 pg/ml) in human plasma, and is the first such method
avoiding immunoenrichment. Specificity of endogenous glucagon quantitation was
assured using a novel approach with a supercharging mobile phase additive to
access a sensitive qualifier SRM. Endogenous glucagon concentrations were within
the expected range, and showed good reproducibility after extended sample
storage. A cross-validation against established immunoassays using physiological
study samples demonstrated some similarities between methods. CONCLUSION: The LC
MS/MS method offers a viable alternative to immunoassays for quantitation of
endogenous glucagon, dosed glucagon and/or dosed GLP-1.
PMID- 28488895
TI - Sleep quality, chronotype, temperament and bipolar features as predictors of
depressive symptoms among medical students.
AB - The assessment of risk factors is a crucial step in the prevention and treatment
of affective disorders and should encompass personal dispositions. The aim of
this study was to assess the value of chronotype and temperament as independent
predictors of depressive symptoms among medical students. The study surveyed 140
students of the Faculty of Medicine with a battery of questionnaires: the Beck
Depression Index (BDI), Hypomania Checklist 32 (HCL-32), Pittsburgh Sleep Quality
Index (PSQI), Chronotype Questionnaire and Eysenck Personality Questionnaire
Revised. The results were tested using Pearson's correlation quotient and general
linear model. Ten percent of the participants demonstrated a BDI score suggestive
of clinically significant depressive symptoms. BDI score correlated positively
with HCL-32 score. A rise in BDI was independently predicted by elevated
Neuroticism and PSQI scores and morningness. Those effects were independent from
each other and from other parameters of the model. The presence of depressive
symptoms might be associated with bipolar features among medical students. Poor
sleep quality predicted depressive symptoms, similarly to Neuroticism and
independently of temperament and chronotype. Future studies on the associations
between personal dispositions and mood disorders among medical students are
required to help identify those at greater risk of developing affective illness.
Effective prophylaxis and early intervention are warranted to ensure better
treatment results.
PMID- 28488896
TI - A sensitive assay for ZYAN1 in human whole blood and urine utilizing positive LC
MS/MS electrospray ionization.
AB - AIM: A sensitive LC-MS/MS method was developed and validated for estimation of
ZYAN1 in human blood/urine. METHODS: An analog internal standard IOX2 along with
ZYAN1 was quantified using selective reaction monitoring in positive mode. The
chromatographic separation was performed by gradient elution with C18 analytical
column (3 um, 50 mm * 2.0 mm) with 4-min run time using an acidified mobile phase
consisting of ammonium formate and acetonitrile. Protein precipitation enabled
extraction of analytes from diluted blood/urine. RESULTS: Calibration curve of
ZYAN1 was linear (2-5000 ng/ml). The recovery of ZYAN1 and IOX2 was between 87
and 104%. Interday and intraday accuracy and precision was found well within the
acceptance criteria. CONCLUSION: The validated assay was applied for clinical
pharmacokinetics of ZYAN1 in healthy volunteers.
PMID- 28488897
TI - Mediation, moderation, and context: Understanding complex relations among
cognition, affect, and health behaviour.
AB - OBJECTIVE: Researchers have historically treated cognition and affect as separate
constructs in motivating health behaviour. We present a framework and empirical
evidence for complex relations between cognition and affect in predicting health
behaviour. Main Outcome, Design and Results: First, affect and cognition can
mediate each other's relation to health behaviour. Second, affect and cognition
can moderate the other's impact. Third, context can change the interplay of
affect and cognition. Fourth, affect and cognition may be indelibly fused in some
psychological constructs (e.g. worry, anticipated regret and reactance). These
four propositions in our framework are not mutually exclusive. CONCLUSION:
Examination of the types of complex relations described here can benefit theory
development, empirical testing of theories and intervention design. Doing so will
advance the understanding of mechanisms involved in regulation of health
behaviours and the effectiveness of interventions to change health behaviours.
PMID- 28488898
TI - Bridging immunogenicity assays for IgG4 therapeutics: mitigating interference
from Fc-Fc interactions.
AB - AIM: A bridging immunogenicity assay for a human IgG4 mAb therapeutic was
transferred to an automation system to increase throughput. However, background
signal increased five- to six-fold during the 6- to 8-h run. RESULTS: Noncovalent
Fc contacts formed between labeled IgG4 drugs in reagent solutions stored during
the automation run. This generated substantial background signal, reducing assay
sensitivity by approximately sixfold. Fc interactions also significantly impacted
the confirmation assay. Fc contacts formed between labeled and unlabeled drug,
significantly increasing signal inhibition (~7-70%) in the 6-h run. CONCLUSION:
Storing labeled antibody solutions separately and combining them immediately
before adding to samples reduced interference from Fc interactions. Preincubation
time for reagent solutions should be strictly controlled for anti-drug antibody
assays with IgG4 drugs to avoid false-positive results.
PMID- 28488899
TI - Lifetime prevalence of psychiatric morbidities, suicidality, and quality of life
in a community population with the bimodal chronotype: A nationwide epidemiologic
study.
AB - Chronotypes are classified as morning, evening, or intermediate, but there are
reports of a bimodal type. This study was undertaken to describe the
characteristics of the bimodal chronotype and to explore relationships between
the bimodal type and psychiatric disorders, fatigue, and quality of life. A total
of 2389 subjects from a Korean national epidemiological survey of psychiatric
disorders responded during face-to-face interviews. The Korean Composite
International Diagnostic Interview was used to diagnose psychiatric disorders,
and the Composite Scale of Morningness was used to assess chronotypes. Among
intermediate-type subjects, those with a positive bimodal index were classified
as bimodal type. In the present study, the proportions of bimodal, morning,
intermediate, and evening types were 4.8%, 10.8%, 73.3%, and 11.1%, respectively.
Distributions of sociodemographic variables were similar for the bimodal and
intermediate types. After controlling for sociodemographic variables, any mood
disorder and major depressive disorder were found to be significantly more
associated with the bimodal type than the morning type, and dysthymic disorder
was significantly more associated with the bimodal type than the intermediate
type. For quality-of-life domains, moderate or extreme pain/discomfort was
complained about more by subjects with the bimodal type than other types. In
summary, the study shows chronotypes differ with respect to their relationships
with mood disorder and quality of life. Before the bimodal type is classified as
a clinically valid type, further investigations are needed to examine its
psychological, physiological, and genetic characteristics.
PMID- 28488900
TI - Isolated polyhydramnios in the third trimester: is a gestational diabetes
evaluation of value?
AB - We evaluated implications of testing for gestational diabetes mellitus (GDM) in
pregnancies complicated by third trimester isolated polyhydramnios with previous
negative diabetes screening test. In this retrospective cohort study of 104
pregnant women with polyhydramnios between 2005 and 2013, all had normal first
trimester fasting glucose and normal glucose challenge test (GCT < 140 mg/dL).
Late onset GDM was diagnosed in five women (4.8%) with isolated polyhydramnios,
one abnormal value in the oral glucose tolerance test (OGTT) was identified in
four additional women (3.8%). No significant differences were found in risk
factors for GDM, mean second trimester GCT (117.5 vs. 107.2 mg/dL, p = 0.38) or
fasting glucose values (82 vs. 86 mg/dL, p = 0.29) between women in the
polyhydramnios group with and without late GDM diagnosis. Moreover, no
significant difference was found in relation to the mode of delivery or birth
weight between the studied groups (3437 +/- 611 vs. 3331 +/- 515 g, p = 0.63).
Diagnosis of third trimester polyhydramnios was not associated with increased
risk for GDM or neonatal complications.
PMID- 28488901
TI - Association of shiftwork and immune cells among police officers from the Buffalo
Cardio-Metabolic Occupational Police Stress study.
AB - Shift workers suffer from a constellation of symptoms associated with disruption
of circadian rhythms including sleep abnormalities, and abnormal hormone
secretion (e.g. melatonin, cortisol). Recent, but limited, evidence suggests that
shift workers have elevated levels of circulating white blood cells (WBCs)
compared to their day working counterparts. Interestingly, recent reviews
highlight the strong linkage between the immune system and circadian rhythms
which includes, but is not limited to, circulating cell populations and
functions. The elevated levels of these WBCs may be associated with the increased
chronic disease risk observed among this group. The purpose of this analysis was
to examine the cross-sectional association between long- and short-term (3, 5, 7,
and 14 days) shiftwork (SW) and counts of WBCs among officers in the Buffalo
Cardio-Metabolic Occupational Police Stress (BCOPS) cohort. Data collection for
this analysis took place among 464 police officers working in Buffalo, New York,
USA between 2004 and 2009. Precise SW histories were obtained using electronic
payroll records. Officers were assigned a shift type based on the shift (i.e.
day, evening, night) that they spent a majority (i.e. >=50%) of their time from
1994 to the data collection date for long-term SW. The same process was applied
to SW over 3, 5, 7, and 14 days prior to data collection. A fasted blood sample
collected in the morning of a non-work day was used for characterization of WBCs
(total), neutrophils, monocytes, lymphocytes, eosinophils, and basophils.
Potential confounding factors included demographic characteristics (e.g. age,
sex, race), occupational characteristics (e.g. rank), health behaviors (e.g.
smoking, alcohol consumption, diet), anthropometrics, and other biomarkers (e.g.
lipids, hemoglobin A1C, leptin). Generalized linear models were used to estimate
least square means of the immune cells according to SW categorization for long-
and short-term SW histories. Compared to the day shift group, those working long
term night shifts had greater absolute numbers of total WBCs, neutrophils,
lymphocytes, and monocytes (all p < 0.05). Those working mainly on the night
shift over 7-days had elevated counts of WBCs, lymphocytes, and monocytes (p <
0.05) compared to those mainly working day shifts. Results based on 3-, 5-, and
14-day SW were similar to the 7-day results. This study corroborates other
studies with similar findings. However, this analysis provided insights into the
effect of both long- and short-term SW on the number of circulating WBCs. SW may
lead to disruption of circadian-influenced components of the immune system, which
in term, may result in various chronic diseases. These findings, plus previous
findings, may provide evidence that SW may lead to immune system dysregulation.
Future research is needed to understand whether increases in immune cells among
shift workers may be associated with the increased disease risk among this group.
PMID- 28488902
TI - Designing augmentative and alternative communication applications: the results of
focus groups with speech-language pathologists and parents of children with
autism spectrum disorder.
AB - PURPOSE: The purpose of this study was to gain insight from speech-language
pathologists (SLPs) and parents of children with autism spectrum disorder (ASD)
regarding appealing features of augmentative and alternative communication (AAC)
applications. METHOD: Two separate 1-hour focus groups were conducted with 8 SLPs
and 5 parents of children with ASD to identify appealing design features of AAC
Apps, their benefits and potential concerns. Participants were shown novel
interface designs for communication mode, play mode and incentive systems.
Participants responded to poll questions and provided benefits and drawbacks of
the features as part of structured discussion. RESULTS: SLPs and parents
identified a range of appealing features in communication mode (customization,
animation and colour-coding) as well as in play mode (games and videos). SLPs
preferred interfaces that supported motor planning and instruction while parents
preferred those features such as character assistants that would appeal to their
child. Overall SLPs and parents agreed on features for future AAC Apps.
CONCLUSION: SLPs and parents have valuable input in regards to future AAC app
design informed by their experiences with children with ASD. Both groups are key
stakeholders in the design process and should be included in future design and
research endeavors. Implications for Rehabilitation AAC applications for the iPad
are often designed based on previous devices without consideration of new
features. Ensuring the design of new interfaces are appealing and beneficial for
children with ASD can potentially further support their communication. This study
demonstrates how key stakeholders in AAC including speech language pathologists
and parents can provide information to support the development of future AAC
interface designs. Key stakeholders may be an untapped resource in the
development of future AAC interfaces for children with ASD.
PMID- 28488903
TI - Versican A-subdomain is required for its adequate function in dermal development.
AB - Versican, a large chondroitin sulfate (CS) proteoglycan, serves as a structural
macromolecule of the extracellular matrix (ECM) and regulates cell behavior. We
determined the function of versican in dermal development using VcanDelta3/Delta3
mutant mice expressing versican with deleted A-subdomain of the N-terminal G1
domain. The mutant versican showed a decreased hyaluronan (HA)-binding ability
and failed to accumulate in the ECM. In the early developmental stage,
VcanDelta3/Delta3 dermis showed a decrease in versican expression as compared
with WT. As development proceeded, versican expression further decreased to a
barely detectable level, and VcanDelta3/Delta3 mice died at the neonatal period
(P0). At P0, VcanDelta3/Delta3 dermis exhibited an impaired ECM structure and
decreased cell density. While the level of collagen deposition was similar in
both genotypes, collagen biosynthesis significantly decreased in
VcanDelta3/Delta3 fibroblasts as compared with that in wild type (WT).
Transforming growth factor beta (TGFbeta) signaling mediated through the Smad2/3
dependent pathway was down-regulated in VcanDelta3/Delta3 fibroblasts and a
reduced TGFbeta storage in the ECM was observed. Microarray analysis revealed a
decrease in the expression levels of transcription factors, early growth response
(Egr) 2 and 4, which act downstream of TGFbeta signaling. Thus, our results
suggest that A-subdomain is necessary for adequate versican expression in dermis
and that versican is involved in the formation of the ECM and regulation of
TGFbeta signaling.
PMID- 28488904
TI - Use of an Outreach Coordinator to Reengage and Retain Patients with HIV in Care.
AB - It is well established that retention in high-quality care and regular visits
with an HIV/AIDS provider improve outcomes for people living with HIV/AIDS
(PLWHA). However, nationally and regionally in South Carolina, retention rates
remain low. We piloted an outreach program focused on characterizing out of care
(OOC) patients to identify PLWHA who were lost to care and attempt reengagement
through phone call, letter, and home visit interventions. Primary outcomes were
reengagement, defined as attendance to a clinic appointment, and retention in
care, defined by the Health Resources and Services Administration (HRSA)
definition (two visits at least 90 days apart in 2015). There were 1242 adult
clinic patients in 2014. A total of 233 patients were included in the OOC cohort,
according to the inclusion criteria. Of these 233, the outreach coordinator found
that a majority of patients, 119 (51%), were lost to care. Reengagement was seen
in 52 (44%) patients lost to care, and among those who reengaged, 26 (50%) were
retained in care in 2015. This report represents one of few interventions that
target reengagement for patients who are lost to care. The use of an outreach
coordinator was successful in reengaging and retaining patients in care. It
represents an uncomplicated intervention, functional within the current clinic
design and available funding structure of the Ryan White grant. Poor engagement
and retention in care continue to be significant problems among PLWHA with
resultant poor clinical outcomes. Continued focus on new interventions to improve
retention in care is necessary to improve clinical outcomes.
PMID- 28488905
TI - Tactical Behaviors in Men's 800-m Olympic and World-Championship Medalists: A
Changing of the Guard.
AB - PURPOSE: To assess the longitudinal evolution of tactical behaviors used to medal
in men's 800-m Olympic Games (OG) or world-championship (WC) events in the recent
competition era (2000-2016). METHODS: Thirteen OG and WC events were
characterized for 1st- and 2nd-lap splits using available footage from YouTube.
Positive pacing strategies were defined as a faster 1st lap. Season's best 800-m
time and world ranking, reflective of an athlete's "peak condition," were
obtained to determine relationships between adopted tactics and physical
condition prior to the championships. Seven championship events provided coverage
of all medalists to enable determination of average 100-m speed and sector pacing
of medalists. RESULTS: From 2011 onward, 800-m OG and WC medalists showed a
faster 1st lap by 2.2 +/- 1.1 s (mean, +/-90% confidence limits; large
difference, very likely), contrasting a possibly faster 2nd lap from 2000 to 2009
(0.5, +/-0.4 s; moderate difference). A positive pacing strategy was related to a
higher world ranking prior to the championships (r = .94, .84-.98; extremely
large, most likely). After 2011, the fastest 100-m sector from 800-m OG and WC
medalists was faster than before 2009 by 0.5, +/-0.2 m/s (large difference, most
likely). CONCLUSIONS: A secular change in tactical racing behavior appears
evident in 800-m championships; since 2011, medalists have largely run faster 1st
laps and have faster 100-m sector-speed requirements. This finding may be
pertinent for training, tactical preparation, and talent identification of
athletes preparing for 800-m running at OGs and WCs.
PMID- 28488906
TI - Factors Affecting Match Outcome in Elite Australian Football: A 14-Year Analysis.
AB - Effects of fixture and team characteristics on match outcome in elite Australian
football were quantified using data accessed at AFLtables.com for 5109 matches
for seasons 2000 to 2013. Aspects of each match included number of days' break
between matches (<=7 d vs >=8 d), location (home vs away), travel status (travel
vs no travel), and differences between opposing teams' mean age, body mass, and
height (expressed as quintiles). A logistic-regression version of the generalized
mixed linear model estimated each effect, which was assessed with magnitude-based
inference using 1 extra win or loss in every 10 matches as the smallest important
change. For every 10 matches played, the effects were days' break, 0.1 +/- 0.3
(90% CL) wins; playing away, 1.5 +/- 0.6 losses; traveling, 0.7 +/- 0.6 losses;
and being in the oldest, heaviest, or shortest, quintile, 1.9 +/- 0.4, 1.3 +/-
0.4, and 0.4 +/- 0.4 wins, respectively. The effects of age and body-mass
difference were not reduced substantially when adjusted for each other. All
effects were clear, mostly at the 99% level. The effects of playing away, travel,
and age difference were not unexpected, but the trivial effect of days' break and
the advantage of a heavier team will challenge current notions about balancing
training with recovery and about team selection.
PMID- 28488907
TI - Prediction: The Modern-Day Sport-Science and Sports-Medicine "Quest for the Holy
Grail".
AB - In high-performance sport, science and medicine practitioners employ a variety of
physical and psychological tests, training and match monitoring, and injury
screening tools for a variety of reasons, mainly to predict performance, identify
talented individuals, and flag when an injury will occur. The ability to
"predict" outcomes such as performance, talent, or injury is arguably sport
science and medicine's modern-day equivalent of the "Quest for the Holy Grail."
The purpose of this invited commentary is to highlight the common
misinterpretation of studies investigating association to those actually
analyzing prediction and to provide practitioners with simple recommendations to
quickly distinguish between methods pertaining to association and those of
prediction.
PMID- 28488908
TI - Choosing, Doing, and Controlling: Implicit Sense of Agency Over Somatosensory
Events.
AB - Sense of agency-a feeling of control over one's actions and their outcomes-might
include at least two components: free choice over which outcome to pursue and
motoric control over the action causing the outcome. We orthogonally manipulated
locus of outcome choice (free or instructed choice) and motoric control (active
or passive movement), while measuring the perceived temporal attraction between
actions and outcomes ( temporal binding) as an implicit marker of agency.
Participants also rated stimulus intensity so that we could measure sensory
attenuation, another possible implicit marker of agency. Actions caused higher or
lower levels of either painful heat or mild electrotactile stimulation. We found
that both motoric control and outcome choice contributed to outcome binding.
Moreover, free choice, relative to instructed choice, attenuated the perceived
magnitude of high-intensity outcomes, but only when participants made an active
movement. Thus, choosing, not just doing, influences temporal binding and sensory
attenuation, though in different ways. Our results show that these implicit
measures of agency are sensitive to both voluntary motor commands and
instrumental control over action outcomes.
PMID- 28488909
TI - First episode indices associated with lifetime chronicity of depression among
formerly depressed participants: an exploratory study.
AB - BACKGROUND: Researchers have found that an earlier age of disorder onset and the
severity of the first depressive episode are associated with recurrence in
depression. Additionally, neuroticism has been shown to be an important factor in
the recurrence of the disorder. AIMS: This exploratory study aimed to replicate
and extend previous research by examining the relationships between features of
the first experienced depressive episode (age of onset, severity), the five
factors of personality, and lifetime chronicity of depression. METHOD: Forty
three previously depressed participants completed measures of personality,
current depression, hopelessness, and perfectionism. Previous depressive episodes
were assessed using a semi-structured interview, and features of these episodes
experienced by participants were recorded. RESULTS: Pearson correlations showed
that depression chronicity, measured in the number of weeks depressed in a
lifetime, was significantly correlated with age of onset and number of symptoms
experienced in the first episode. Personality measures were not significantly
associated with depression chronicity. CONCLUSION: Earlier and more severe first
episodes of depression may play an important role in the recurrence of the
disorder. Future research should focus on replication and determining the causal
role of these features.
PMID- 28488910
TI - Methadone-Induced Neurotoxicity in Advanced Cancer: A Case Report.
AB - Methadone use as a second-line agent for severe cancer-related pain is increasing
in the field of hospice and palliative care. It has a number of qualities that
make its use favorable, including lack of known active metabolites and presumed
relative safety from adverse effects such as opioid-induced neurotoxicity (OIN).
This article describes a case of a patient undergoing treatment of severe cancer
related pain who developed OIN in the setting of oral methadone use. As the use
of methadone increases, more research into its pharmacologic and pharmacokinetic
properties will be necessary.
PMID- 28488911
TI - Comparison Between Video-Assisted and Open Lateral Neck Dissection for Papillary
Thyroid Carcinoma with Lateral Neck Lymph Node Metastasis: A Prospective
Randomized Study.
AB - BACKGROUND: The safety and oncologic completeness of video-assisted lateral neck
dissection (VALND) for papillary thyroid carcinoma (PTC) with lateral neck lymph
node metastasis (LNM) have been reported. However, their generalization has
remained limited because the advantages and drawbacks are not well demonstrated.
MATERIALS AND METHODS: A total of 64 patients with PTC and unilateral lateral
neck LNM who underwent total thyroidectomy with central compartment neck
dissection and lateral neck dissection (LND) were prospectively enrolled. They
were randomly assigned to the video-assisted (VA) group (n = 32) or open group (n
= 32) and were treated either by VALND or conventional open LND, respectively. We
compared operating time, complications, oncologic completeness, postoperative
pain, and cosmetic results between the two groups. RESULTS: The complication rate
and oncologic completeness, including the results of radioactive iodine scans,
mean number of lymph nodes retrieved, and mean postoperative serum thyroglobulin
levels, were similar between the groups. Postoperative pain was observed less
frequently after surgery in the VA group (P < .0001). Cosmetic results evaluated
by a verbal response scale and a numeric rating scale were in favor of the VA
group (P < .0001 and P = .0004, respectively). Total operating time was 176 +/-
16 minutes in the VA group and 161 +/- 16 minutes in the open group (P = .0003).
CONCLUSIONS: VALND yielded complication and oncologic completeness rates that
were similar to those of open LND. However, VALND resulted in less postoperative
pain and better cosmetic results.
PMID- 28488913
TI - Relationship Between Pretraining Subjective Wellness Measures, Player Load, and
Rating-of-Perceived-Exertion Training Load in American College Football.
AB - CONTEXT: The relationship between pretraining subjective wellness and external
and internal training load in American college football is unclear. PURPOSE: To
examine the relationship of pretraining subjective wellness (sleep quality,
muscle soreness, energy, wellness Z score) with player load and session rating of
perceived exertion (s-RPE-TL) in American college football players. METHODS:
Subjective wellness (measured using 5-point, Likert-scale questionnaires),
external load (derived from GPS and accelerometry), and s-RPE-TL were collected
during 3 typical training sessions per week for the second half of an American
college football season (8 wk). The relationship of pretraining subjective
wellness with player load and s-RPE training load was analyzed using linear mixed
models with a random intercept for athlete and a random slope for training
session. Standardized mean differences (SMDs) denote the effect magnitude.
RESULTS: A 1-unit increase in wellness Z score and energy was associated with
trivial 2.3% (90% confidence interval [CI] 0.5, 4.2; SMD 0.12) and 2.6% (90% CI
0.1, 5.2; SMD 0.13) increases in player load, respectively. A 1-unit increase in
muscle soreness (players felt less sore) corresponded to a trivial 4.4% (90% CI
8.4, -0.3; SMD -0.05) decrease in s-RPE training load. CONCLUSION: Measuring
pretraining subjective wellness may provide information about players' capacity
to perform in a training session and could be a key determinant of their response
to the imposed training demands American college football. Hence, monitoring
subjective wellness may aid in the individualization of training prescription in
American college football players.
PMID- 28488912
TI - A high level of estrogen-stimulated proteins selects breast cancer patients
treated with adjuvant endocrine therapy with good prognosis.
AB - BACKGROUND: Adjuvant endocrine therapy has significantly improved survival of
estrogen receptor alpha (ER)-positive breast cancer patients, but around 20%
relapse within 10 years. High expression of ER-stimulated proteins like
progesterone receptor (PR), Bcl-2 and insulin-like growth factor receptor I (IGF
IR) is a marker for estrogen-driven cell growth. Therefore, patients with high
tumor levels of these proteins may have particularly good prognosis following
adjuvant endocrine therapy. PATIENTS AND METHODS: Archival tumor tissue was
available from 1323 of 1396 Danish breast cancer patients enrolled in BIG 1-98, a
randomized phase-III clinical trial comparing adjuvant letrozole, tamoxifen or a
sequence of the two drugs. Immunohistochemical staining for ER, HER-2, PR, Bcl-2
and IGF-IR was performed and determined by Allred scoring (ER, PR and Bcl-2) or
HercepTest (HER-2 and IGF-IR). RESULTS: Data on all five markers were available
from 969 patients with ER-positive, HER-2-negative tumors. These patients were
classified in ER activity groups based on the level of PR, Bcl-2 and IGF-IR. High
ER activity profile was found in 102 patients (10.5%) and compared with the
remaining patients, univariate and multivariate analysis revealed HR (95% CI) and
p values for disease-free survival (DFS) of 2.00 (1.20-3.22), 0.008 and 1.70
(1.01-2.84), 0.04 and for the overall survival (OS) of 2.33 (1.19-4.57), 0.01 and
1.90 (0.97-3.79), 0.06, respectively. The high ER activity profile did not
disclose difference in DFS or OS according to treatment with tamoxifen or
letrozole (p = .06 and .09, respectively). CONCLUSIONS: Stratifying endocrine
treated patients in ER activity profile groups disclosed that patient with high
ER activity profile (10.5%) had significantly longer DFS and OS, and the profile
was an independent marker for DFS. High ER activity is a marker for estrogen
driven tumor growth. We suggest further analyses to disclose whether the ER
activity profile or other markers associated with estrogen-driven growth may be
used to identify ER-positive high-risk breast cancer patients who can be spared
adjuvant chemotherapy.
PMID- 28488914
TI - Decitabine treatment of multiple extramedullary acute myeloid leukemia
involvements after essential thrombocytemia transformation.
PMID- 28488915
TI - Unilateral Recession-Resection Surgery for Infantile Esotropia: Survival of Motor
Outcomes and Postoperative Drifts.
AB - PURPOSE: To outline the short- and long-term motor outcomes of unilateral medial
rectus muscle recession and lateral rectus muscle resection for the correction of
moderate angle infantile esotropia. METHODS: A retrospective study of 109
consecutive patients with moderate angle infantile esotropia treated with graded
unilateral recession-resection surgery. Criteria for successful motor outcome
included alignment +/-10Delta from orthophoria. Outcome evaluation was a
comparison of successful alignment versus an overcorrection or undercorrection at
eight weeks postoperatively as well as on the final follow-up examination.
RESULTS: The mean preoperative deviation was 35.5 prism diopters (Delta) and mean
follow-up time was 4.9 years. At the eight-week postoperative examination, 99
patients (89.9%) were successfully aligned, as opposed to 75 of 95 patients
(78.9%) at the final postoperative visit (P=0.041). There was no statistically
significant difference between the rate of early versus late undercorrections
(7.3% versus 12.5%, P=0.267) or overcorrections (2.7% versus 8.3%, P=0.125). Ten
patients had an esotropic drift over time and 10 patients had an exotropic drift.
Recurrent esotropia was associated with high hyperopia and presumed infantile
esotropia diagnostic entity. The Kaplan-Meier estimate of survivorship of a
successful motor outcome was 75.5% at five years and 71% at 15 years
postoperatively. The mean response to surgery was 2.9Delta per mm of muscle
recessed and resected and was positively related to the preoperative angle of
deviation (R=0.615). CONCLUSIONS: The unilateral recession-resection procedure
for the correction of infantile esotropia is shown to be associated with a
favorable survival of motor outcomes and a relatively balanced rate of
undercorrections versus overcorrections tending to be maintained through the
follow-up period.
PMID- 28488916
TI - Observing the fate of tRNA and its modifications by nucleic acid isotope labeling
mass spectrometry: NAIL-MS.
AB - RNA in yeast, especially rRNA and tRNA are heavily modified to fulfill their
function in protein translation. Using biosynthetic stable isotope labeled
internal standards we quantified 12 modified nucleosides in tRNA from S.
cerevisiae over 24 hours. We observed different quantities of modified
nucleosides in dependence of the growth phase. To elucidate the underlying
mechanism of the observed tRNA modification profile adaptation, it is necessary
to distinguish the pre-existing tRNA pool and its modifications from newly
synthesized tRNAs. By combination of 2 differentially isotope labeled media we
developed NAIL-MS, nucleic acid isotope labeling coupled mass spectrometry.
During the yeast growth cycle we observe dilution of pre-existing tRNAs by newly
synthesized tRNAs by the growing number of cells. tRNA was found to be highly
stable with only little degradation over the observed period. The method was
further used to quantify the levels of modified nucleosides in the original and
new tRNA pools. By addition of deuterium-labeled methionine, we could observe the
incorporation of new methyl marks on pre-existing tRNAs. For 2'-O-methylcytidine
(Cm) we observed a global increase in log phase. We identified extensive 2'-OH
cytidine methylation of the pre-existing tRNAs and the new tRNAs which masks an
actual decrease of pre-existing Cm. In contrast, global 5-methylcytidine (m5C)
levels decreased during growth due to a drop in m5C quantities in the original
tRNA pool. The NAIL-MS data suggests different mechanisms for tRNA modification
adaptation depending on the individual modification observed. With this new tool
it is possible to follow the fate of methylated RNAs during growth and
potentially compare the impact of different stress conditions on the
epitranscriptome.
PMID- 28488917
TI - Contrasting Gender and Combat Versus Military Sexual Traumas: Psychiatric Symptom
Severity and Morbidities in Treatment-Seeking Veterans.
AB - BACKGROUND: Military sexual trauma (MST) and military combat trauma (MCT) are
significant risk factors for posttraumatic stress disorder (PTSD). However, no
studies have directly contrasted the clinical profiles of Veterans between
military-related traumas. Moreover, a notable gender difference in the likelihood
of trauma exposure limits our ability to disentangle gender and trauma type.
MATERIALS AND METHODS: To address these gaps, we aimed at (1) contrasting
psychiatric complaints in Veterans with MST versus MCT exposure and (2)
investigating gender differences in Veterans with MST histories. Treatment
seeking Veterans (N = 563) completed semi-structured diagnostic interviews and
self-report assessments of PTSD, depressive, and dissociative symptoms. RESULTS:
Psychiatric complaints and morbidity were notable after all military-associated
traumas, although those seeking care for MST-related events demonstrated more
severe PTSD, depressive, and dissociative symptoms and were more likely to meet
criteria for non-PTSD anxiety and psychotic disorders. In contrast, few gender
related differences were noted between male and female Veterans with histories of
MST. CONCLUSIONS: The experience of MST may reduce typically observed gender
related buffering effects for certain conditions.
PMID- 28488918
TI - The Relationship Between Variables in Wearable Microtechnology Devices and
Cricket Fast-Bowling Intensity.
AB - To date, the monitoring of fast-bowling workloads across training and competition
environments has been limited to counting total balls bowled. However, bowling at
faster velocities is likely to require greater effort while also placing greater
load on the bowler. This study investigated the relationship between prescribed
effort and microtechnology outputs in fast bowlers to ascertain whether the
technology could provide a more refined measure of workload. Twelve high
performing fast bowlers (mean +/- SD age 20.3 +/- 2.2 y) participated in the
study. Each bowler bowled 6 balls at prescribed bowling intensities of 60%, 70%,
85%, and 100%. The relationships between microtechnology outputs, prescribed
intensity, and ball velocity were determined using polynomial regression. Very
large relationships were observed between prescribed effort and ball velocity for
peak PlayerLoadTM (R = .83 +/- .19 and .82 +/- .20). The PlayerLoad across lower
ranges of prescribed effort exhibited a higher coefficient of variation (CV) (60%
= 19.0% [17.0-23.0%]), while the CV at higher ranges of prescribed effort was
lower (100% = 7.3% [6.4-8.5%]). Routinely used wearable microtechnology devices
offer opportunities to examine workload and intensity in cricket fast bowlers
outside the normal metrics reported. They offer a useful tool for prescribing and
monitoring bowling intensity and workload in elite fast bowlers.
PMID- 28488919
TI - Nuanced aesthetic emotions: emotion differentiation is related to knowledge of
the arts and curiosity.
AB - The ability to distinguish between emotions is considered indicative of well
being, but does emotion differentiation (ED) in an aesthetic context also reflect
deeper and more knowledgeable aesthetic experiences? Here we examine whether
positive and negative ED in response to artistic stimuli reflects higher fluency
in an aesthetic domain. Particularly, we test whether knowledge of the arts and
curiosity are associated with more fine-grained positive and negative aesthetic
experiences. A sample of 214 people rated their positive and negative feelings in
response to various artworks including positive and negative themes. Positive ED
was associated with the embracing sub-trait of curiosity that reflects engagement
and enjoyment of novelty and complexity, but was unrelated to artistic knowledge
and perceived comprehension. Negative ED was associated with higher curiosity and
particularly more knowledge of the arts. This relationship was mediated by
appraised comprehension suggesting that deeper engagement with art, by those with
more art knowledge, is associated with more fine-grained emotional experiences.
This finding extends ED beyond well-being research and suggests that more nuanced
emotional experiences are more likely for those with expertise in the arts and
motivation for exploration.
PMID- 28488920
TI - Two-Stage Explantation of a Magnetic Lower Esophageal Sphincter Augmentation
Device Due to Esophageal Erosion.
AB - INTRODUCTION: Implanting a magnetic lower esophageal sphincter augmentation
device (LINX, Torax Medical) has become an increasingly common option in the
surgical management of gastroesophageal reflux disease. As the enthusiasm for
placing this device increases, experience in the management of device-related
complications-including erosion-is necessary. METHODS: We report a staged
approach to LINX removal in a 64-year-old female with symptoms of odynophagia
secondary to partial erosion of a LINX device into the esophagus. RESULTS: The
patient had a 12-bead LINX device placed in 2011 at an outside, international
facility. In late 2013, she began experiencing symptoms of odynophagia. An
esophagogastroduodenoscopy at our institution in October 2015 demonstrated two
metallic beads eroding through the distal esophageal lumen. An elective
endoscopic removal of the two visible beads was performed. A postoperative
esophagram confirmed that there was no resulting esophageal perforation. The
patient noted mild improvement in her symptoms. After a 12-week period to allow
for complete healing, the remaining 10 beads of the LINX device were explanted
laparoscopically without complication. No further procedures were undertaken. At
2 months' follow-up, the patient noted complete resolution of her symptoms.
CONCLUSION: Transmural erosion of the LINX device into the esophageal lumen is a
rare occurrence, with only five such complications reported in the published
literature. We present the first account of LINX explantation for esophageal
erosion in the United States. We demonstrated that a staged laparoendoscopic
approach to LINX removal in these cases is feasible with minimal morbidity.
PMID- 28488921
TI - Sex Differences in World-Record Performance: The Influence of Sport Discipline
and Competition Duration.
AB - The current review summarizes scientific knowledge concerning sex differences in
world-record performance and the influence of sport discipline and competition
duration. In addition, the way that physiological factors relate to sex
dimorphism is discussed. While cultural factors played a major role in the rapid
improvement of performance of women relative to men up until the 1990s, sex
differences between the world's best athletes in most events have remained
relatively stable at approximately 8-12%. The exceptions are events in which
upper-body power is a major contributor, where this difference is more than 12%,
and ultraendurance swimming, where the gap is now less than 5%. The physiological
advantages in men include a larger body size with more skeletal-muscle mass, a
lower percentage of body fat, and greater maximal delivery of anaerobic and
aerobic energy. The greater strength and anaerobic capacity in men normally
disappear when normalized for fat-free body mass, whereas the higher hemoglobin
concentrations lead to 5-10% greater maximal oxygen uptake in men with such
normalization. The higher percentage of muscle mass in the upper body of men
results in a particularly large sex difference in power production during upper
body exercise. While the exercise efficiency of men and women is usually similar,
women have a better capacity to metabolize fat and demonstrate better
hydrodynamics and more even pacing, which may be advantageous, in particular
during long-lasting swimming competitions.
PMID- 28488922
TI - Predicting prognosis in patients with advanced cancer: A prospective study.
AB - BACKGROUND: Prognosis is one of the most challenging questions with which
physicians are confronted. Accuracy in the prediction of survival is necessary
for clinical, ethical, and organizational reasons. AIM: Evaluate young doctors'
clinical prediction of survival and the aids they could get: expert opinion,
Palliative Prognostic score, and Palliative Prognostic Index. DESIGN:
Prospective, observational study. SETTING/PARTICIPANTS: Advanced cancer patients
under observation of an inhospital palliative care team, from April to July 2014.
A total of 38 patients were included, mostly male (65.8%), average age 68.5
years. Average survival time was 24 days. Follow-up concluded with death or after
90 days. RESULTS: Young doctors' clinical prediction of survival was adequate at
10.5%, with 55.3% severe errors in an optimistic direction. Palliative care
experts were more adequate (23.7%) and made less severe errors (42.1%).
Palliative Prognostic score and Palliative Prognostic Index were even more
adequate (47% and 55%, respectively) and made even less severe errors (0% and
11%, respectively). The best correlation with observed survival was achieved when
palliative care experts used palliative prognostic score ( rs = -0.629; p <
0.01). CONCLUSION: Young doctors' clinical prediction of survival is often
inadequate. Palliative Prognostic score, which includes clinical prediction of
survival, calculated by palliative care experts had the best performance. Our
results support the recommendation of using clinical prediction of survival
together with prognostic scores.
PMID- 28488923
TI - The effects of life review interventions on spiritual well-being, psychological
distress, and quality of life in patients with terminal or advanced cancer: A
systematic review and meta-analysis of randomized controlled trials.
AB - BACKGROUND: Life review interventions have been used to alleviate psycho
spiritual distress in people near the end of life. However, their effectiveness
remains inconclusive. AIM: To evaluate the effects of therapeutic life review on
spiritual well-being, psychological distress, and quality of life in patients
with terminal or advanced cancer. DESIGN: A systematic review according to the
Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology.
DATA SOURCES: Five databases were searched from their respective inception
through February 2017 for relevant randomized controlled trials. The effects of
therapeutic life review were pooled across the trials. Standardized mean
differences were calculated for the pooled effects. Heterogeneity was assessed
using the I2 test. Study quality was assessed using the Cochrane criteria.
RESULTS: Eight randomized controlled trials met the inclusion criteria. The
pooled results suggested a desirable effect of therapeutic life review on the
meaning of life domain of spiritual well-being (standardized mean difference =
0.33; 95% confidence interval, 0.12 to 0.53), general distress (standardized mean
difference = -0.32; 95% confidence interval, -0.55 to -0.09), and overall quality
of life (standardized mean difference = 0.35; 95% confidence interval, 0.15 to
0.56) when compared to usual care only. Of the three outcomes examined, only the
pooled effect on overall quality of life remained statistically significant at
follow-ups up to 3 months after the intervention (standardized mean difference =
0.82; 95% confidence interval, 0.47 to 1.18). CONCLUSIONS: Therapeutic life
review is potentially beneficial for people near the end of life. However, the
results should be interpreted with caution due to the limited number of
randomized controlled trials and associated methodological weaknesses. Further
rigorously designed randomized controlled trials are warranted.
PMID- 28488924
TI - Effects of Caffeine on Countermovement-Jump Performance Variables in Elite Male
Volleyball Players.
AB - PURPOSE: To examine the effects of a moderate dose of caffeine in elite male
volleyball players on countermovement-jump (CMJ) performance, as well as temporal
concentric- and eccentric-phase effects. METHODS: Ten elite male volleyball
players took part in 2 experimental days via a randomized crossover trial 1 wk
apart in which they ingested either 5 mg/kg of caffeine or a placebo in double
blind fashion. Heart rate and blood pressure were measured at rest and 60 min
postingestion. Afterward, subjects also performed 3 CMJ trials 60 min
postingestion, of which the average was used for further analysis. They filled
out a questionnaire on possible side effects 24 h posttrial. RESULTS: Caffeine
intake, compared with placebo, increased CMJ peak concentric force (6.5% +/-
6.4%; P = .01), peak power (16.2% +/- 8.3%; P < .01), flight time (5.3% +/- 3.4%;
P < .01), velocity at peak power (10.6% +/- 8.0%; P < .01), peak displacement
(10.8% +/- 6.5%; P < .01), peak velocity (12.6% +/- 7.4%; P < .01), peak
acceleration (13.5% +/- 8.5%; P < .01), and the force developed at peak power
(6.0% +/- 4.0%; P < .01) and reduced the time between peak power and peak force
(16.7% +/- 21.6%, P = .04). Caffeine increased diastolic blood pressure by 13.0%
+/- 8.9% (P < .05), whereas no adverse side effects were found. CONCLUSIONS: The
ingestion of 5 mg/kg of anhydrous caffeine improves overall CMJ performance
without inducing side effects.
PMID- 28488925
TI - Strategies to address the shortcomings of commonly used advanced chronic heart
failure descriptors to improve recruitment in palliative care research: A
parallel mixed-methods feasibility study.
AB - BACKGROUND: Recruitment challenges contribute to the paucity of palliative care
research with advanced chronic heart failure patients. AIM: To describe the
challenges and outline strategies of recruiting advanced chronic heart failure
patients. DESIGN: A feasibility study using a pre-post uncontrolled design.
SETTING: Advanced chronic heart failure patients were recruited at two nurse-led
chronic heart failure disease management clinics in Ireland Results: Of 372
patients screened, 81 were approached, 38 were recruited (46.9% conversion to
consent) and 25 completed the intervention. To identify the desired population, a
modified version of the European Society of Cardiology definition was used
together with modified New York Heart Association inclusion criteria to address
inter-study site New York Heart Association classification subjectivity. These
modifications substantially increased median monthly numbers of eligible patients
approached (from 8 to 20) and median monthly numbers recruited (from 4 to 9).
Analysis using a mortality risk calculator demonstrated that recruited patients
had a median 1-year mortality risk of 22.7 and confirmed that the modified
eligibility criteria successfully identified the population of interest. A
statistically significant difference in New York Heart Association classification
was found in recruited patients between study sites, but no statistically
significant difference was found in selected clinical parameters between these
patients. CONCLUSION: Clinically relevant modifications to the European Society
of Cardiology definition and strategies to address New York Heart Association
subjectivity may help to improve advanced chronic heart failure patient
recruitment in clinical settings, thereby helping to address the paucity of
palliative care research this population.
PMID- 28488926
TI - Removal of glyphosate and aminomethylphosphonic acid from synthetic water by
nanofiltration.
AB - The removal of glyphosate and aminomethylphosphonic acid (AMPA) with synthetic
water was carried out on a lab-scale nanofiltration unit using two membranes, NFX
and NFW. The presence of humic acid and some inorganic matters (CaCl2 and NaCl)
was tested in the experiment. The results demonstrate that NFX exhibits better
separation performance than NFW. The herbicide filtration is found to have little
effect on the permeate flux as compared to transmembrane pressure. Intermediate
concentrations of NaCl act positively on foulant separation, and an increment of
3.3-5.4 percentage points in foulant rejection is obtained with the addition of
100 mg/L of NaCl. In Contrast, CaCl2 has negative effect on foulant separation
during nanofiltration. Humic acid alone shows little influence on the rejection
performance, whereas it is slightly improved in the coexistence of humic acid and
CaCl2. The nanofiltration technology proves to be a good approach to treat the
problem of pesticide micropollution in a one-step process. This work clearly
shows that the composition of the water matrices may influence the efficiency of
the nanofiltration process in terms of the separation of the micropollutants.
PMID- 28488927
TI - Distinct Motivational Effects of Contingent and Noncontingent Rewards.
AB - When rewards are available, people expend more energy, increasing their
motivational vigor. In theory, incentives might drive behavior for two distinct
reasons: First, they increase expected reward; second, they increase the
difference in subjective value between successful and unsuccessful performance,
which increases contingency-the degree to which action determines outcome.
Previous studies of motivational vigor have never compared these directly. Here,
we indexed motivational vigor by measuring the speed of eye movements toward a
target after participants heard a cue indicating how outcomes would be
determined. Eye movements were faster when the cue indicated that monetary
rewards would be contingent on performance than when the cue indicated that
rewards would be random. But even when the cue indicated that a reward was
guaranteed regardless of speed, movement was still faster than when no reward was
available. Motivation by contingent and certain rewards was uncorrelated across
individuals, which suggests that there are two separable, independent components
of motivation. Contingent motivation generated autonomic arousal, and unlike
noncontingent motivation, was effective with penalties as well as rewards.
PMID- 28488928
TI - Do subjective assessments of running patterns reflect objective parameters?
AB - Running patterns are often categorized into subgroups according to common
features before data analysis and interpretation. The Volodalen(r) method is a
simple field-based tool used to classify runners into aerial or terrestrial using
a 5-item subjective rating scale. We aimed to validate the Volodalen(r) method by
quantifying the relationship between its subjective scores and 3D biomechanical
measures. Fifty-four runners ran 30 s on a treadmill at 10, 12, 14, 16, and 18 km
h-1 while their kinematics were assessed subjectively using the Volodalen(r)
method and objectively using 3D motion capture. For each runner and speed, two
researchers scored the five Volodalen(r) items on a 1-to-5 scale, which addressed
vertical oscillation, upper-body motion, pelvis and foot position at ground
contact, and footstrike pattern. Seven 3D biomechanical parameters reflecting the
subjective items were also collected and correlated to the subjective scores.
Twenty-eight runners were classified as aerial and 26 as terrestrial. Runner
classification did not change with speed, but the relative contribution of the
biomechanical parameters to the subjective classification was speed dependent.
The magnitude of correlations between subjective and objective measures ranged
from trivial to very large. Five of the seven objective parameters significantly
differed between aerial and terrestrial runners, and these parameters
demonstrated the strongest correlations to the subjective scores. Our results
support the validity of the Volodalen(r) method, whereby the visual appreciation
of running gait reflected quantifiable objective parameters. Two minor
modifications to the method are proposed to simplify its use and improve
agreement between subjective and objective measures.
PMID- 28488929
TI - Mobile Diagnostic Units for Rural Patients in Colombia.
AB - BACKGROUND: The literature on the use of mobile diagnostic units for the adult
population is limited. This is a report for the first time in Colombia (Latin
America) on the use of mobile diagnostic units for patients in rural areas and
resolution of complex cases through telemedicine. INTRODUCTION: Telemedicine is
an alternative because it takes advantage of advances in telecommunications and
technology for the provision of health services to patients in rural areas of a
country. MATERIALS AND METHODS: A pilot program for mobile patient diagnosis was
developed in three rural areas of central Colombia. The mobile unit was named
Mobile dIagnostiC Unit (MICU). The unit includes a medical stretcher, dresser,
washbasin, computer, videoconference equipment, satellite connectivity, and
digital medical equipment: electrocardiogram, stethoscope, oximeter, and
thermometer. RESULTS: The number of patients attended during the 3 days of
activity was 108, ~36 each day. None of the patients (100%) was familiar with
digital diagnostic tools and telemedicine. The entire population who attended
(100%) was satisfied with the care, health education, and diagnosis received.
DISCUSSION: Our case report shows that the use of MICUs with the support of
telemedicine offers benefit to the rural population in the geographic zone chosen
in Colombia. CONCLUSIONS: With greater coverage and access for patients to health
services via mobile telemedicine units, it is possible to increase the quality of
care.
PMID- 28488930
TI - Preparation of liposome bearing disulfide proteinoid and its reduction-responsive
release property.
AB - Egg phosphatidylcholine (Egg PC) liposome bearing a disulfide proteinoid
exhibited a reduction-responsive release property. Proteinoid composed of Asp,
Leu, and cystamine (Prot(ALC)) and Asp and Leu (Prot(AL)) were synthesized by
thermal condensation, confirmed by Raman, FT-IR, 1H NMR and 13C NMR spectroscopy.
Egg PC liposome bearing the proteinoid was prepared by a film hydration and
sonication method. The fluorescence quenching of dye (i.e. calcein) loaded in
liposome bearing the proteinoid was 68.1-78.1%. The mean hydrodynamic diameter of
liposome bearing the proteinoid was less than 200 nm and it decreased with
increasing amount of the proteinoid. On the TEM photo, multi-lamellar vesicles
were observed and the vesicle diameter was 100-300 nm. At all the phospholipid to
proteinod ratios tested (i.e. 1:0.01, 1:0.02, and 1:0.05 (w/w)), the release
degree in 12 h of dye loaded in liposome bearing Prot(AL) was less than 2%, and
it was almost the same regardless of dithiothreitol (DTT, a reducing agent)
concentration (i.e. 0, 10, and 20 mM). Whereas the release degree of dye loaded
in liposome bearing Prot(ALC) was 1.5-8.4% and it was significantly dependent on
DTT concentration.
PMID- 28488931
TI - Lightweight bricks manufactured from ground soil, textile sludge, and coal ash.
AB - Reuse of textile sludge as construction materials has been proved to an economic
and environmental friendly strategy to mitigate its disposal problems. Previous
studies have illustrated the successful fabrication of common fired bricks using
textile sludge as a partial replacement of clay, but no such a specific work was
focused on the feasibility of manufacturing lightweight bricks from textile
sludge. In this study, a strategy involving the mixing of ground soil, textile
sludge, and coal ash as the raw materials for the successful production of
lightweight bricks is presented. Coal ash and ground soil have different
combustible contents but similar main chemical composition, which facilitates the
separable adjustment of these two factors of the raw material mixture to achieve
their suitable values at the same time, and thus results in the successful
manufacture of lightweight bricks. To meet the requirement for compressive
strength and consume textile sludge as more as possible, an optimal ratio of the
raw materials was obtained as textile sludge:coal ash:ground soil = 20:20:60. The
brick products manufactured from this ratio show a compressive strength of 13.7
MPa, bulk density of 1.47 g cm-3, water absorption of 14.6%, and volumetric
shrinkage of 13.61% after sintering. The results of toxicity characteristic
leaching procedure test show that the heavy metal concentrations in the leachates
of the brick products are very low, which also satisfy the regulations. This
study provides a feasible and economical technology for the treatment of textile
sludge.
PMID- 28488932
TI - Powassan/Deer Tick Virus and Borrelia Burgdorferi Infection in Wisconsin Tick
Populations.
AB - Powassan/Deer Tick Virus (POWV/DTV) is an emerging cause of arboviral
neuroinvasive disease in the upper Midwest. These studies describe the prevalence
and geographic distribution of Wisconsin ticks carrying POWV/DTV as well as the
high frequency of Ixodes scapularis ticks coinfected with both POWV/DTV and
Borrelia burgdorferi, the causative agent of Lyme disease. These findings suggest
that concurrent transmission of POWV/DTV and B. Burgdorferi from coinfected ticks
is likely to occur in humans.
PMID- 28488933
TI - Zebrafish as a Screening Model for Testing the Permeability of Blood-Brain
Barrier to Small Molecules.
AB - The objective of this study was to evaluate the permeability of small molecules
into the brain via the blood-brain barrier in zebrafish and to investigate the
possibility of using this animal model as a screening tool during the early
stages of drug discovery. Fifteen compounds were used to understand the
permeation into the brain in zebrafish and mice. The ratio of brain-to-plasma
concentration was compared between the two animal models. The partition
coefficient (Kp,brain), estimated using the concentration ratio at designated
times (0.167, 0.25, 0.5, or 2 h) after oral administrations (per os, p.o), ranged
from 0.099 to 5.68 in zebrafish and from 0.080 to 11.8 in mice. A correlation was
observed between the Kp,brain values obtained from the zebrafish and mice,
suggesting that zebrafish can be used to estimate Kp,brain to predict drug
penetration in humans. Furthermore, in vivo transport experiments to understand
the permeability glycoprotein (P-gp) transporter-mediated behavior of loperamide
(LPM) in zebrafish were performed. The zebrafish, Kp,brain,30min of LPM was
determined to be 0.099 +/- 0.069 after dosing with LPM alone, which increased to
0.180 +/- 0.115 after dosing with LPM and tariquidar (TRQ, an inhibitor of P-gp).
In mouse, the Kp,brain,30min of LPM was determined to be 0.080 +/- 0.004 after
dosing with LPM alone and 0.237 +/- 0.013 after dosing with LPM and TRQ. These
findings indicate that the zebrafish could be used as an effective screening tool
during the discovery stages of new drugs to estimate their distribution in the
brain.
PMID- 28488935
TI - Seroprevalence and Factors Associated with Toxoplasma gondii Infections in Sheep
in Latvia: Latvian Dark Headed Sheep Breed Associated with Higher Seroprevalence.
AB - Toxoplasma gondii is a protozoan parasite with both public health and veterinary
importance. The aims of our study were to estimate the T. gondii seroprevalence
in sheep in Latvia and to evaluate potential risk factors for seropositivity. The
blood samples investigated were collected from 1039 sheep from 84 farms between
January 2012 and April 2013. The sera were tested for immunoglobulin G antibodies
against T. gondii using an in-house enzyme-linked immunosorbent assay. Antibodies
against T. gondii were detected in 179 (17.2%) of the sheep, and at least one
seropositive sheep was found on 37 (44.0%) of the farms. The seroprevalence was
significantly higher in adult (over 1 year old) sheep than in juveniles-the adult
sheep had 1.8 times higher odds to test seropositive than did the juveniles. The
seroprevalence was significantly higher in Latvian Dark Headed sheep than in
crossbreed and German Merino sheep. Sheep from large herds (with more than 100
sheep), as well as those from farms with cattle, had higher odds to test
seropositive, whereas the presence of poultry on the farm appeared as a
protecting factor. The results show that sheep in Latvia are commonly exposed to
T. gondii.
PMID- 28488934
TI - The Zebrafish curly fry Is Required for Proper Centrosome and Mitotic Spindle
Assembly.
AB - The zebrafish curly fry (cfy) mutation leads to a dramatic increase in mitotic
index and cell death starting during neural tube formation. The mutant phenotype
is cell autonomous and does not result from defects in apical/basal polarity
within the neuroepithelium. The increase in mitotic index could be due to
increased proliferation or cell cycle arrest in mitosis. cfy embryos were
analyzed to examine these two possibilities. By labeling embryos with a pulse of
BrdU and anti-phospho-histone 3 and examining the DNA content by fluorescence
activated cell sorting, we show that cfy mutants exhibit no increase in
proliferation, but a significant increase in the number of cells arrested in
mitosis. Furthermore, time-lapse microscopy in vivo confirmed that a great
majority of dividing cells arrest during mitosis and that these mitotically
arrested cells die in cfy embryos. Finally, immunostaining and confocal
microscopy in cfy mutant embryos revealed that mitotic cells in mutants contain
aberrant centrosomes and often exhibit monopolar spindles, thereby leading to
mitotic cell cycle arrest. Our results suggest that the cfy gene is required for
proper centrosome assembly and mitotic spindle formation, therefore critical for
normal cell division.
PMID- 28488936
TI - Long-Term Social Recognition Memory in Zebrafish.
AB - In species in which individuals live in stable social groups, individual
recognition is expected to evolve to allow individuals to remember past
interactions with different individuals and adjust future behavior toward them
accordingly. Thus, social memory is expected to be a ubiquitous component of
social cognition of social species. However, few studies have investigated the
occurrence of social memory in non-mammals. Here we evaluated the ability of
zebrafish (Danio rerio) to recognize different conspecifics and to retain this
information in long lasting (i.e. 24 h) memories. We used a social discrimination
paradigm, adapted from mouse studies, in which the focal individual meets two
pairs of conspecifics in two consecutive days: one conspecific is the same in
both days and the other is different between days 1 and 2. If animals have the
ability to discriminate between different conspecifics, it is predicted that they
will spend more time exploring the novel than the familiar (i.e. already seen in
day 1) conspecific. In this study, zebrafish with access to both olfactory and
visual conspecific cues exhibited consistent recognition of a previously
encountered (familiar) conspecific after a 24 h delay. This result supports the
hypothesis that long-term social memory, previously described in mammals, is also
present in zebrafish, hence extending the evidence for the presence of this type
of memory to teleost fish.
PMID- 28488937
TI - Traditional balance and slackline training are associated with task-specific
adaptations as assessed with sensorimotor tests.
AB - The purpose of this study was to measure alterations in sensorimotor skills and
balance resulting from slackline training and conventional balance training.
Forty-three physically fit subjects were randomized into three groups. Two groups
practiced three times a week for 15 minutes, including at least once supervised
session, on the slackline or perform conventional balance training for 6 weeks.
The control group was not allowed to perform any balance training. Before and
after the intervention, the subjects underwent sensorimotor and strength tests.
The results of our intra-class correlation analysis showed that the stability
parameters from the multifunctional training device (MFT, 0.7), the height during
the countermovement jump (CMJ, 0.95) and the maximum force (0.88) during leg
press showed excellent reliability. A post hoc comparison indicated a larger
effect of conventional training (almost 11% reduction in MFT stability) compared
with slackline training in group-wide comparisons of the pre- to the post
training measurements. The factor analysis showed that stability and sensorimotor
assessment using MFT were correlated, as were height during CMJ and maximal force
during leg press, which represented dynamic strength. Because CMJ had the highest
intra-class correlation value, it was chosen over maximum force from leg press.
For these reasons, only two out of nine measured parameters, namely MFT stability
and CMJ, were analysed across groups. The only observed difference between the
two groups was MFT stability (slackline - 1.5%, conventional - 13%), whereas the
improvement of CMJ was the same (slackline + 3%, conventional + 3%). It can be
concluded that slacklining is partly complementary to conventional sensorimotor
training.
PMID- 28488938
TI - Aerobic sludge granulation for simultaneous anaerobic decolorization and aerobic
aromatic amines mineralization for azo dye wastewater treatment.
AB - In this study, the capability of using aerobic granules to undergo simultaneous
anaerobic decolorization and aerobic aromatic amines degradation was demonstrated
for azo dye wastewater treatment. An integrated acclimation-granulation process
was devised, with Mordant Orange 1 as the model pollutant. Performance tests were
carried out in a batch column reactor to evaluate the effect of various operating
parameters. The optimal condition was to use 1.0-1.7 mm (1.51 +/- 0.33 mm)
granules, 5 g/L biomass, and 4000 mg/L organics as nutrient; and supplement the
wastewater with 1 mg/L dissolved oxygen. This led to a dye mineralization of 61
+/- 2%, an anaerobic dye removal of 88 +/- 1%, and an aerobic aromatic amines
removal of 70 +/- 3% within 48 h. This study showed that simultaneous
anaerobic/aerobic process by aerobic granules could be a possible alternative to
the conventional activated sludge process.
PMID- 28488940
TI - Marathon Specialization in Elites: A Head Start for Africans.
AB - PURPOSE: To assess differences in event-specific specialization between elite
African and non-African male marathon runners based on age, performance, and
career length. METHODS: The top 90 African marathoners from 2001 to 2015 were
compared with the top 90 non-African marathoners from the same time period across
various markers related to specialization age, performance, and career length.
Independent t tests were used to identify significant differences (P < .05)
between the African and non-African groups. Linear regression was used to explore
the relationship between first half-marathon and best full-marathon performance.
A 1-way ANOVA and Bonferroni correction was used to assess differences in
specialization age and rates of performance improvement and decline. RESULTS:
African marathoners were found to specialize, reach peak levels of performance,
and retire at younger ages than non-African marathoners (P < .001). In addition,
African marathoners were found to be faster at these same career time points and
in half-marathon performance (P < .001). There was no significant difference in
the number of career marathons run between groups, but African marathoners were
found to race more frequently than non-African marathoners (P < .001). Half
marathon performance was positively correlated with marathon performance (r2 =
.67). Marathon athletes who specialized at early ages experienced significantly
higher rates of improvement than those who specialized at older ages. (P < .05).
CONCLUSIONS: The findings suggest that elite African marathoners achieve a
greater level of performance at younger ages than their non-African counterparts.
Furthermore, current marathon talent-identification practice may benefit from
using half-marathon performance.
PMID- 28488939
TI - Differences in morning-evening type and sleep duration between Black and White
adults: Results from a propensity-matched UK Biobank sample.
AB - Biological evidence suggests that ethno-racial differences in morning-evening
type are possible, whereby Blacks may be more likely to be morning type compared
to Whites. However, population-level evidence of ethno-racial difference in
morning-evening type is limited. In an earlier study, we reported that morning
type was more prevalent in Blacks compared to Whites in the United Kingdom (UK)
Biobank cohort (N = 439 933). This study aimed to determine if these ethno-racial
differences persisted after accounting for an even broader range of social,
environmental and individual characteristics and employing an analytic approach
that simulates randomization in observational data, propensity score modeling.
Data from UK Biobank participants whose self-identified race/ethnicity was
Black/Black British or White; who did not report daytime napping, shift work or
night shift work; who provided full mental health information; and who were
identified using propensity score matching were used (N = 2044). Each sample was
strongly matched across all social, environmental and individual characteristics
as indicated by absolute standardized mean differences <0.09 for all variables.
The prevalence of reporting nocturnal short, adequate and long sleep as well as
morning, intermediate and evening type among Blacks (n = 1022) was compared with
a matched sample of Whites (n = 1022) using multinomial logistic regression
models. Blacks had a 62% greater odds of being morning type [odds ratio (OR) =
1.620, 95% confidence interval (CI): 1.336-1.964, p < .0001] and a more than
threefold greater odds of reporting nocturnal short sleep (OR = 3.453, 95% CI:
2.846-4.190, p < .0001) than Whites. These data indicate that the greater
prevalence of morning type and short nocturnal sleep in Blacks compared to Whites
is not fully explained by a wide range of social and environmental factors. If
sleep is an upstream determinant of health, these data suggest that ethno
racially targeted public health sleep intervention strategies are needed.
PMID- 28488941
TI - A-V block as presentation of cardiac amyloid: prominent infiltration of
conduction tissue revealed by endomyocardial biopsy.
PMID- 28488942
TI - Goat Model for Direct Visualizing the Effectiveness of Detaching Sinus Mucosa in
Real Time During Crestal Maxillary Sinus Floor Elevation.
AB - The procedure of crestal maxillary sinus floor elevation presents a great
challenge to the field of implant dentistry. Due to the limited visualization in
this procedure, the effectiveness of detaching sinus mucosa could not be assessed
in real time. We recently developed an ex vivo goat sinus model by cutting the
goat residual skulls along four lines determined from computerized tomography
(CT) scans, extracting the maxillary premolar or molar teeth, and preparing
implant socket in the maxilla. The generated ex vivo goat sinus models exposed
the maxilla and the whole maxillary sinus mucosa, thus enabling real-time
observation of detaching maxillary sinus mucosa via directly visualizing the
working situation of sinus lift tool in the models and directly measuring the
length of detached mucosa and space volume generated under the elevated sinus
mucosa. One commercially available umbrella-shaped sinus lift curette was used to
detach the maxillary sinus mucosa to evaluate the effectiveness of the ex vivo
goat sinus models. The results showed that this curette could detach the sinus
mucosa 3.75 mm in length in the mesiodistal direction and 2.81 mm in the buccal
palatal direction. Moreover, a space volume of 52.7 MUl could be created under
the elevated sinus mucosa in the goat ex vivo models. All the experimental
results suggested that this ex vivo goat sinus model might be useful in the
evaluation of improved or newly designed sinus lift tools for elevating the
maxillary sinus mucosa via the crestal approach.
PMID- 28488943
TI - Effect of blue-blocking glasses in major depressive disorder with sleep onset
insomnia: A randomized, double-blind, placebo-controlled study.
AB - Blue wavelengths form the portion of the visible electromagnetic spectrum that
most potently regulates circadian rhythm. We hypothesized that wearing blue
blocking (BB) glasses in the evening may influence circadian rhythm disturbances
in patients with major depressive disorder (MDD), resulting in improved sleep and
mood. We used a randomized placebo-controlled double-blinded design. Patients
with MDD with sleep onset insomnia were randomly assigned to wearing either BB
glasses or clear glasses (placebo). Patients were instructed to wear the glasses
from 20:00 hours until bedtime for 2 weeks. We assessed sleep state (sleep
quality on a visual analog scale, the Morningness-Eveningness Questionnaire
[MEQ], and a sleep diary) and depressive symptoms at baseline and after 2 weeks.
Data were analyzed with a full analysis set. In total, 20 patients were randomly
assigned to the BB and placebo groups (BB group, n = 10; placebo group, n = 10).
There were three dropouts (BB group, n = 1; placebo group, n = 2). At baseline,
sleep quality, sleep latency (assessed via a sleep diary), and antipsychotics use
differed between the groups. To take account of these differences, the baseline
sleep state or depressive symptoms and antipsychotics use were used as covariates
in the later analysis. The change scores for sleep quality did not show a
significant improvement in the BB group compared with the placebo group (mean
[standard deviation, SD] scores for BB versus placebo: 36.1 [31.7] versus 16.2
[15.1], p = 0.43), although half of the BB group showed a clear improvement in
sleep quality. The change in MEQ scores did not significantly differ between the
groups (p = 0.14), although there was a trend of a shift to morning type in the
BB group (3.10 [4.95] points) and to evening type in the placebo group (0.50
[3.89] points). There were no statistically significant changes in depressive
symptoms in either group. Across both groups, 40% of the participants reported
pain or discomfort from wearing the glasses, which were available in only one
size. Thus, the failure to find significant differences may have resulted from
the glasses used in this study. Glasses fitted to individual patients may improve
efficacy and safety. Replication of the study with a larger sample size and size
adjustable glasses is needed.
PMID- 28488944
TI - A Scalable and Accurate Method for Quantifying Vector Genomes of Recombinant
Adeno-Associated Viruses in Crude Lysate.
AB - Increasing interest and application of recombinant adeno-associated viruses
(rAAVs) in basic and clinical research have urged efforts to improve rAAV
production quality and yield. Standard vector production workflows call for
genome titration of purified vectors at the endpoint of production to assess
yield. Unfortunately, quality control measures for preparations during mid
production steps and economical means to assess the fidelity of multiple batches
of rAAV preparations are lacking. Here we describe a scalable and accurate method
for the direct quantitative polymerase chain reaction (qPCR) titration of rAAV
genomes in crude lysate. Lysate samples are pretreated with DNase I to remove
vector and packaging plasmid DNAs, followed by proteinase K to release
endonuclease-resistant packaged viral genomes and to proteolyze factors inherent
to crude lysates that can impinge upon quantitative PCR efficiencies. We show
that this method is precise, scalable, and applicable for vector genome
titrations of both single-stranded and self-complementary AAV genomes
irrespective of serotype differences-a major limitation for standard lysate
transduction methods that indirectly screen for vector packaging efficiency. Our
described method therefore represents a significant improvement to rAAV vector
production in terms of alleviating time and cost burdens, in-process quality
control assessment, batch/lot monitoring in large-scale preparations, and good
manufacturing practices.
PMID- 28488945
TI - Tropical pulmonary eosinophilia masquerading as asthma in a 5-year-old girl.
AB - Tropical pulmonary eosinophilia (TPE) is an exaggerated immunological response to
filarial antigens mainly seen in adults in endemic areas and is uncommonly
reported in children. The diagnosis is frequently delayed as it mimics asthma
clinically, while the chest radiograph might show miliary mottling which is often
confused with that in pulmonary tuberculosis. A 5-year-old girl presented with
episodes of nocturnal cough, wheeze, low grade fever and breathlessness for the
previous 4 months and was being treated for asthma. The absolute eosinophil count
was markedly raised (53 * 109/L) with prominent bilateral infiltrates on the
chest radiograph. Serology for microfilaria and a test for microfilaria antigens
were positive and the patient showed a dramatic response to diethylcarbamazine,
which confirmed the diagnosis of TPE. TPE is an important differential diagnosis
of asthma especially in endemic areas.
PMID- 28488946
TI - Laparoscopic Reconstruction in Post-Tubercular Urinary Tract Strictures:
Technical Challenges.
AB - BACKGROUND: Genitourinary tuberculosis still continues to plague developing
countries and is a significant cause of morbidity as well as mortality in the
developing world. At present, nearly 55% of the patients of genitourinary
tuberculosis (GUTB) need surgical management. Owing to the presence of dense
adhesions and loss of normal anatomical planes, GUTB was considered to be a
contraindication to laparoscopic surgery. However, recent literature shows
laparoscopy to be feasible in GUTB. Our study aimed at identifying the challenges
in laparoscopic urinary tract reconstructive surgery in genitourinary
tuberculosis-related urinary tract obstruction. MATERIALS AND METHODS: The
details of 6 patients who underwent different types of laparoscopic
reconstructive surgery for genitourinary tuberculosis-related urinary tract
obstruction from January 2014 to December 2015 were reviewed. Baseline
characteristics, indications of surgery, type of surgery, operative duration,
blood loss, and follow-up details were noted. All patients received
antitubercular treatment before surgery as per the direct observed treatment
short-course regimen followed in our country. RESULTS: We performed one bilateral
laparoscopic pyeloplasty, one unilateral laparoscopic pyeloplasty, two
laparoscopic ureteroneocystostomies, and two ureteroureterostomies. Difficulty
was encountered during dissection owing to the presence of adhesions, but
conversion to open surgery was not done in five cases. Dense adhesions adjacent
to the common iliac vessels necessitated conversion to open surgery in one of the
ureteroureterostomies. Stenting was done in all the patients. All patients had
uneventful postoperative recovery. Functional imaging following stent removal
showed unobstructed tracer flow, showing successful operative outcome.
CONCLUSIONS: Our study showed that laparoscopic reconstructive surgery is
feasible in genitourinary tuberculosis despite the presence of adhesions that may
pose a challenge to dissection. This is in contrast to the previous studies which
conclude that genitourinary tuberculosis is a relative contraindication to
laparoscopic surgery.
PMID- 28488947
TI - Translation control: Learning from viruses, again.
AB - Viruses are powerful tools to uncover cellular processes. Through viral studies
we have recently identified a novel translational control mechanism that involves
the DEAD-box helicase Dhh1/DDX6 and RNA folding within coding sequences (CDSs).
All Dhh1-dependent mRNAs, viral and cellular ones, (i) contain long and highly
structured CDSs, (ii) are directly bound by Dhh1 with a specific pattern, (iii)
are activated at the translation initiation step and (iv) express proteins
associated with the endoplasmic reticulum. The obtained results uncover a novel
layer of translation regulation associated with translation at the endoplasmic
reticulum conserved from yeast to humans and hijacked by viruses.
PMID- 28488948
TI - The effectiveness of augmented versus standard individual placement and support
programs in terms of employment: a systematic literature review.
AB - BACKGROUND: The Individual Placement and Support (IPS) program is a well-studied
vocational rehabilitation program. Although it is more effective than usual care,
it is not effective for everyone. This offers an opportunity for program
improvement. AIMS: This systematic literature review examines the state of
knowledge regarding the effectiveness of augmented versus standard IPS for people
with severe mental illness (SMI). We address the questions, "What IPS
augmentations have been tested?" and "What is the evidence for the effectiveness
of augmented IPS versus standard IPS in terms of employment?" METHODS: This
systematic literature review used publically available peer-reviewed studies
published between January 2002 and January 2016 in either: (1) Medline Current,
(2) Medline In-process, (3) PsycINFO, (4) Econlit or (5) Web of Science. RESULTS:
5718 unique citations were identified; seven articles from five studies were
included. Of these studies, four were rated as having moderate risk of bias and
one as having high risk. CONCLUSIONS: The results suggest that augmentations of
IPS focusing on cognitive and psychosocial skills training, may have additional
effects to standard IPS. Areas in need of further research related to the process
and targeting of those interventions are discussed.
PMID- 28488949
TI - Decrease Hospital Spending: There's an App for That! A Retrospective Analysis of
Implementation of a Mobile Resident Handbook on Hospital Costs and Disposition.
AB - BACKGROUND: Patient care involves time sensitive decisions. Matching a patient's
presenting condition with possible diagnoses requires proper assessment and
diagnostic tests. Timely access to necessary information leads to improved
patient care, better outcomes, and decreased costs. INTRODUCTION: This study
evaluated objective outcomes of the implementation of a novel Resident Handbook
Application (RHAP) for smart phones. METHODS: The RHAP included tools necessary
to make proper assessments and to order appropriate tests. The RHAPs
effectiveness was accessed using the Military Health System Military Mart
database. This database includes patient specific aggregate data, including
diagnosis, patient demographics, itemized cost, hospital days, and disposition
status. Multivariable analysis was used to compare before and after RHAP
implementation, controlling for patient demographics and diagnosis. Internal
medicine admission data were used as a control group. RESULTS: There was a
statistically significant decrease in laboratory costs and a strong trend toward
statistically significant decreases in the cost of radiology performed after
implementation of RHAP (p value of <0.02 and <0.07, respectively). There was also
a decrease in hospital days (3.66-3.30 days), in total cost per admission
($18,866-$16,305), and in cost per hospital day per patient ($5,140-$4,936).
During the same time period a Control group had no change or increases in these
areas. CONCLUSIONS: The use of the RHAP resulted in decreases in costs in a
variety of areas and a decrease in hospital bed days without any apparent
negative effect upon patient outcomes or disposition status.
PMID- 28488950
TI - Is Ross Syndrome an Autoimmune Entity? A Case Series of 11 Patients.
AB - BACKGROUND: Ross syndrome is diagnosed by the presence of segmental anhidrosis,
areflexia, and tonic pupils. Fewer than 60 cases have been described in
literature so far. There have been reports of presence of antibodies in such
patients, suggesting an autoimmune pathogenesis. METHODS: We describe the
clinical profile in this case series of 11 patients with Ross syndrome and
discuss the current status of autoimmunity in its pathogenesis and the
management. RESULTS: Of the 11 patients with Ross syndrome there was an almost
equal sex distribution (male:female ratio was 1.17:1) and the mean age of onset
of symptoms was 26 years. Patients took an average of 6 years to present to a
tertiary center. Sixty-three percent of the patients presented with complaints of
excessive sweating, whereas only 27% had complaints of decreased sweating over a
particular area of the body. Only 45% of the patients had the complete triad of
Ross syndrome, which included segmental anhidrosis, tonic pupil, and absent
reflexes. Eighty-nine percent of the patients had documented absent sympathetic
skin response on electromyography. The various markers of autoimmunity were
negative in all patients who were investigated for the same in this series.
Ninety percent of the patients were managed conservatively. CONCLUSIONS: These
findings suggest that, in Ross syndrome, generalized injury to ganglion cells or
their projections are not purely autoimmune-mediated.
PMID- 28488951
TI - Treatment Outcomes in 1p19q Co-deleted/Partially Deleted Gliomas.
AB - BACKGROUND: Radiotherapy with procarbazine, lomustine, and vincristine improves
overall survival (OS) in patients with 1p19q co-deleted anaplastic
oligodendroglioma/anaplastic oligoastrocytoma. METHODS: This retrospective
analysis investigated outcomes in patients with 1p19q co-deleted/partially
deleted oligodendroglioma, oligoastrocytoma, anaplastic oligodendroglioma, or
anaplastic oligoastrocytoma. OS and progression-free survival (PFS) were analyzed
using the Kaplan-Meier method and prognostic factors using the Cox proportional
hazard model. RESULTS: A total of 106 patients (between December 1997 and
December 2013) were included. Median age was 40 years (19-66), 58 were male
(55%), Eastern Cooperative Oncology Group performance status was 0 in 80 patients
(75%). 1p19q status was co-deleted in 66 (62%), incompletely co-deleted in 27
(25%), and 1p or 19q loss alone in four (4%) and nine (8%) patients,
respectively. Isocitrate dehydrogenase-1 R132H mutation was found in 67 of 85
patients with sufficient material. Upfront treatment was given in 72 (68%)
patients and temozolomide alone in 52 (49%). Median time to radiotherapy in 47
patients (44%) was 34.7 months and 41.2 months in 9 patients with co
deleted/incompletely co-deleted anaplastic oligodendroglioma/anaplastic
oligoastrocytoma who received upfront temozolomide alone. Median OS was not
reached and 5-year OS was 91% for all groups (median follow-up, 5.1 years). On
multivariable analysis for all patients, receipt of therapy upfront versus none
(p=0.04), PS 1 versus 0 (p<0.001) and 1p19q co-deletion/incomplete deletion
versus 1p or 19q loss alone (p=0.005) were prognostic for PFS. Isocitrate
dehydrogenase-1 status was not prognostic for PFS. CONCLUSIONS: With similar
survival patterns in low-grade/anaplastic gliomas, molecular characteristics may
be more important than histological grade. Longer follow-up and results of
prospective trials are needed for definitive guidance on treatment of these
patients.
PMID- 28488952
TI - Aneurysm Tears Caused by an Aneurysm Clip Springing from the Clip Applier.
AB - We experienced two cases in which aneurysm clips sprang from the applier. In case
1, a subdural haematoma from a ruptured anterior cerebral artery aneurysm was
detected. When the clip was opened for final positioning, it suddenly sprang from
the applier and ruptured the aneurysm. In case 2, the clip suddenly sprang from
the applier as the surgeon opened the applier to clip an unruptured anterior
cerebral aneurysm. These accidental phenomena are rare but dangerous. We present
these cases to help prevent similar occurrences in the future. Video recordings
of actual procedures can point to potential mechanisms and help reduce the
incidence of this complication.
PMID- 28488953
TI - Atypical Meningioma: Referral Patterns, Treatment and Adherence to Guidelines.
AB - OBJECTIVE: To determine the referral rate to radiation oncologist (RO), use of
postoperative radiotherapy (PORT) and the impact of a clinical practice guideline
(CPG) on patients with atypical meningioma (AM). METHODS: A retrospective review
of meningioma patients (n=526) treated between 2003 and 2013 was undertaken.
Patients' characteristics, extent of surgical resection (EOR), RO referral, PORT,
date and treatment of first recurrence were collected for all patients >18 years
with a new diagnosis of AM after surgical resection (n=83). Progression free
survival (PFS) and overall survival (OS) according to EOR were assessed by the
Log-Rank test of Kaplan-Meier survival. RESULTS: Median age was 57 years. EOR was
gross total (GTR) in 44 patients, subtotal (STR) in 36 patients and 3 patients
had unknown EOR. RO referral rate was 26.5% (n=22); 5 patients initially had GTR
and 17 had STR. Only 7 patients received PORT. At a median follow up time of 29
months, recurrences occurred in 28 patients, 4 had GTR, 21 had STR and 3 had an
unknown EOR. With PORT, 2 patients developed recurrence. 5-year PFS was 62% after
GTR and 33% after STR (P=0.002). 5-year OS was 92% after GTR and 83% after STR
(P=0.45). CONCLUSION: In this cohort with AM, RO referral rate was low and was
not influenced by the CPG. Use of PORT was also low. Given the lack of conclusive
evidence supporting PORT in such patients, a multidisciplinary approach,
including RO consultation, is needed to provide patients with optimal and
individualised care.
PMID- 28488954
TI - Isolation of a novel orthobunyavirus from bat flies (Eucampsipoda africana).
AB - The Bunyaviridae family comprises viruses causing diseases of public and
veterinary health importance, including viral haemorrhagic and arboviral fevers.
We report the isolation, identification and genome characterization of a novel
orthobunyavirus, named Wolkberg virus (WBV), from wingless bat fly ectoparasites
(Eucampsipoda africana) of Egyptian fruit bats (Rousettus aegyptiacus) in South
Africa. Complete genome sequence data of WBV suggests it is most closely related
to two bat viruses (Mojui dos Campos and Kaeng Khoi viruses) and an arbovirus
(Nyando virus) previously shown to infect humans. WBV replicates to high titres
in VeroE6 and C6-36 cells, characteristic of mosquito-borne arboviruses. These
findings expand our knowledge of the diversity of orthobunyaviruses and their
insect vector host range.
PMID- 28488955
TI - Reporting transfusion-related acute lung injury by clinical and preclinical
disciplines.
AB - BACKGROUND: Disciplines involved in diagnosing transfusion-related acute lung
injury (TRALI) report according to a "one-hit" theory. However, studies showed
that patients with an underlying condition are at increased risk of the
development of TRALI. We investigated whether accumulating evidence on the "two
hit" theory has changed the practice of reporting TRALI. MATERIALS AND METHODS:
Departments of haematology, haemovigilance, transfusion medicine, intensive care
and anaesthesiology from all Dutch hospitals with at least five beds equipped for
mechanical ventilation were invited to participate in an online survey. Using
clinical vignettes with conjoint analysis we investigated the effect of patients'
age, admission diagnosis, type and number of transfusions and presence of risk
factors for acute lung injury on TRALI reporting. A positive beta-coefficient
indicated a higher likelihood of reporting TRALI. RESULTS: We received 129
questionnaires (response rate 74%). Respondents were more likely to report TRALI
in younger patients, if symptoms developed within 2 hours of transfusion and if
patients had received multiple transfusions. Sepsis and the presence of a risk
factor for acute lung injury reduced the inclination to report. Transfusion
medicine physicians and haemovigilance staff no longer took the age of
transfusion products into account in their diagnostic considerations on TRALI.
DISCUSSION: We conclude that the multidisciplinary team involved in TRALI
reporting, still considers TRALI a "one-hit" event, despite accumulating evidence
that supports the "two-hit" theory. These results suggest that the patients most
at risk of developing TRALI are not reported to the blood bank.
PMID- 28488956
TI - Introduction of thromboelastometry-guided administration of fresh-frozen plasma
is associated with decreased allogeneic blood transfusions and post-operative
blood loss in cardiopulmonary-bypass surgery.
AB - BACKGROUND: Cardiac surgery is frequently associated with excessive blood loss
requiring multiple blood transfusions which are, in turn, associated with
increased morbidity and mortality. We evaluated the effectiveness of rotational
thromboelastometry (ROTEM(r))-guided administration of fresh-frozen plasma (FFP)
with regards to blood loss, transfusion requirements, and major post-operative
complications. MATERIALS AND METHODS: Coagulation management in 68 prospective
patients undergoing cardiac surgery with cardiopulmonary bypass was based on a
treatment algorithm guided by ROTEM(r) measurements. The primary end-point was
blood loss at 24 hours after surgery. Secondary end-points were: (i) need for
allogeneic blood products after cardiopulmonary bypass and 24 hours post
operatively, and (ii) post-operative complications until discharge. The results
were compared with those of a retrospective, control group of 69 patients who
received empirical coagulation management before implementation of the ROTEM(r)
guided algorithm. RESULTS: Although patients with significantly lower haemoglobin
levels received less packed red blood cells (PRBC) (840 vs 1,120 mL; p=0.031) and
FFP (480 vs 720 mL; p=0.007) after introduction of the ROTEM(r) algorithm, the
intra-operative blood loss and post-operative haemoglobin levels were similar in
the ROTEM(r) and the retrospective control groups. In addition to significantly
reduced blood loss and decreased requirements for PRBC (30.8 vs 62.3%; p<0.001)
and FFP (25.0 vs 56.5%; p<0.001), the amounts of PRBC (315 vs 840 mL; p<0.001)
and FFP (480 vs 840 mL; p=0.001) received during the first 24 hours after surgery
were significantly reduced in the ROTEM(r) group, as was the duration of post
operative hospitalisation. DISCUSSION: Compared with empirical treatment, timely
ROTEM(r)-guided FFP administration during cardiac surgery can reduce not only
overall blood product use and blood loss but also the duration of
hospitalisation.
PMID- 28488957
TI - Cumulative erythrocyte damage in blood storage and relevance to massive
transfusions: selective insights into serial morphological and biochemical
findings.
AB - Elucidating the precise mechanisms of cumulative red cell damages during storage
and the potential harmful consequences after transfusion are achievable by
exacting laboratory science and well-defined clinical studies in progress.
Accordingly, for larger magnitude blood transfusions (i.e. 8-12 U in 24 hours),
the quality of the stored blood and its characterisation are of special academic
and clinical importance. Our main objectives in this review are to illuminate
facets of the red cell storage lesion for prolonged storage (0-42 days) by
concentrating on various hallmarks of the disorder: 1) identifying and
characterising serial markers of the progressive lesion with respect to red cell
dysmorphology, deformability, haemolytic fragility and dysfunction both in
storage and the microcirculation; and 2) relevant biochemical findings of redox
status correlated to oxidative stress of erythrocyte proteins. This is
accomplished in part by reliance on advanced metabolomic and proteomic
technologies using various sophisticated tools such as high pressure liquid
chromatography in combination with mass spectrometry of proteins and small
molecule metabolites. It is anticipated that these sophisticated methodologies
and the experimental results therein shall lead to further advances in the
quality improvement of red cell storage.
PMID- 28488958
TI - Strategies to identify candidates for D variant genotyping.
AB - BACKGROUND: RhD variants have altered D epitopes and/or decreased antigen copies
per red cell. Individuals carrying these variants may test antigen negative,
weakly positive, or positive by serology, and may or may not be at risk of
alloimmunisation after exposure. There have been recommendations to perform RHD
genotyping of patients, pregnant women and females of childbearing potential with
serological weak D phenotype, to guide prophylactic use of Rh immune globulin
(RhIG), and better conserve D-negative blood products. The purpose of this study
was to evaluate the performance of a set of empirical criteria to identify such
patients. MATERIALS AND METHODS: A two-method strategy of gel testing (GT) and
tube testing (TT) was used for Rh typing of patients with no historical blood
type in the present institution. A monoclonal-polyclonal blend anti-D was used
for Rh typing by TT at immediate spin. Three empirical criteria were used to
identify candidates for genotyping: C1: discrepancy between the two test methods
and a GT reaction strength >2+ stronger than TT; C2: weak serological reaction,
defined as reaction strength <=2+ regardless of testing method if both GT and TT
were performed or reaction strength <=2+ if only GT was performed, or reaction
strength <=1+ if only TT was performed; C3: presence of anti-D in D-positive
patients with no history of RhIG use in the preceding 3 months and in whom
alloanti-D is suspected. RESULTS: Overall, 50 patients, ranging from newly born
to 93 years old, were identified. Genomic testing confirmed D variants in 49/50
cases with a positive predictive value of 98%. DISCUSSION: This two-method
strategy is a powerful screening tool for identifying candidates for RHD
genotyping. This strategy meets the current requirements of two blood type
determinations/two specimens in pre-transfusion testing while simultaneously
identifying candidates for RHD genotyping with a minimal increase in work load
and cost.
PMID- 28488959
TI - Temperature-dependent haemolytic propensity of CPDA-1 stored red blood cells vs
whole blood - Red cell fragility as donor signature on blood units.
AB - BACKGROUND: To preserve cellular integrity and avoid bacterial growth, storage
and transfer of blood and blood products follow strict guidelines in terms of
temperature control. We evaluated the impact of ineligible warming of whole blood
donations on the quality of blood components. MATERIALS AND METHODS: One-hundred
and twenty units of whole blood (WB) from eligible blood donors were collected in
CPDA-1 and stored at 4+/-2 degrees C. During shipment to the blood processing
centre, a gradual warming up to 17 degrees C was recorded within a period of
less than eight hours. The warmed units were processed to packed red blood cells
(PRBCs) or stored as WB units at 4+/-2 degrees C. In-bag haemolysis, osmotic
fragility (mean corpuscular fragility, MCF) and bacterial growth were assessed in
blood and blood components throughout the storage period. RESULTS: Normal basal
and early storage levels of haemolysis were recorded in both PRBC and WB units.
Thereafter, PRBCs exhibited higher average in-bag haemolysis and MCF index
compared to the WB units throughout the storage. Moreover, 14.3 and 52.4% of the
PRBC units exceeded the upper permissible limit of 0.8% haemolysis at the middle
(1.220+/-0.269%) or late (1.754+/-0.866%) storage period, respectively. MCF index
was similar in all PRBCs at the middle of storage but significantly lower in the
non-haemolysed compared to the haemolysed units of PRBCs on the last days. The
fragility of stored RBCs was proportional to the donor-related values of day 2
samples (r=0.861, p<10-32). In the qualified PRBCs, MCF was correlated with
haemolysis at every time point of the storage period (r=0.332, p<0.050).
Bacterial growth was detected by blood culture in two units of PRBCs. DISCUSSION:
Transient, gradient warming of whole blood from 4 to 17 degrees C led to
increased incidence of in-bag haemolysis in PRBC but not in WB units. Haemolysis
is a multi-parametric phenotype of stored blood, and MCF is a donor-related and
highly dynamic measure that can, in part, predict the storage lesion.
PMID- 28488960
TI - Towards pathogen inactivation of red blood cells and whole blood targeting viral
DNA/RNA: design, technologies, and future prospects for developing countries.
AB - Over 110 million units of blood are collected yearly. The need for blood products
is greater in developing countries, but so is the risk of contracting a
transfusion-transmitted infection. Without efficient donor screening/viral
testing and validated pathogen inactivation technology, the risk of transfusion
transmitted infections correlates with the infection rate of the donor
population. The World Health Organization has published guidelines on good
manufacturing practices in an effort to ensure a strong global standard of
transfusion and blood product safety. Sub-Saharan Africa is a high-risk region
for malaria, human immunodeficiency virus (HIV), hepatitis B virus and syphilis.
Southeast Asia experiences high rates of hepatitis C virus. Areas with a tropical
climate have an increased risk of Zika virus, Dengue virus, West Nile virus and
Chikungunya, and impoverished countries face economical limitations which hinder
efforts to acquire the most modern pathogen inactivation technology. These
systems include Mirasol(r) Pathogen Reduction Technology, INTERCEPT(r), and
THERAFLEX(r). Their procedures use a chemical and ultraviolet or visible light
for pathogen inactivation and significantly decrease the threat of pathogen
transmission in plasma and platelets. They are licensed for use in Europe and are
used in several other countries. The current interest in the blood industry is
the development of pathogen inactivation technologies that can treat whole blood
(WB) and red blood cell (RBC). The Mirasol system has recently undergone phase
III clinical trials for treating WB in Ghana and has demonstrated some efficacy
toward malaria inactivation and low risk of adverse effects. A 2nd-generation of
the INTERCEPT(r) S-303 system for WB is currently undergoing a phase III clinical
trial. Both methodologies are applicable for WB and components derived from
virally reduced WB or RBC.
PMID- 28488961
TI - Effect of storage period of red blood cell suspensions on helper T-cell
subpopulations.
AB - BACKGROUND: The aim of this study was to investigate the immunological
alterations that occur during the storage of erythrocyte suspensions which may
lead to transfusion-related immunomodulation following allogeneic blood
transfusion. MATERIALS AND METHODS: One part of the erythrocyte suspensions
obtained from donors was leucoreduced while the other part was not. The
leucoreduced (LR) and non-leucoreduced (NL) erythrocyte suspensions were then
further divided into three equal amounts which were stored for 0, 21 or 42 days
prior to measurements, by enzyme-linked immunosorbent assays, of cytokine levels
in their supernatants. T-helper (Th) lymphocyte subgroups and gene expression
were analysed in the NL erythrocyte suspensions by flow cytometry and real-time
polymerase chain reaction, respectively. Results were compared to those of
storage day 0. RESULTS: By day 21, the number of Th2 cells had increased
significantly and the numbers of Th1, Th22 and Treg cells had decreased
significantly in the NL erythrocyte suspensions. On day 42 the numbers of Th2 and
Treg cells in the NL suspensions were significantly increased while the number of
Th1 cells was significantly decreased. The levels of transcription factors
(TBX21, GATA3, and SPI.1) were significantly decreased on days 21 and 42, and
AHR, FOXP3 and RORC2 levels were significantly increased on day 42 in NL
erythrocyte suspensions. The decrease in interleukin-22 and increase in
transforming growth factor-beta levels found in NL erythrocyte suspensions on day
21 were statistically significant. Elevated levels of interleukin-17A were found
in both LR and NL erythrocyte suspensions on day 42. DISCUSSION: Our results
suggest that allogeneic leucocytes and cytokines may play significant roles in
the development of transfusion-related immunomodulation.
PMID- 28488962
TI - Strategies for reducing the risk of transfusion-transmitted leishmaniasis in an
area endemic for Leishmania infantum: a patient- and donor-targeted approach.
AB - BACKGROUND: In the Balearic Islands, as in other areas of the Mediterranean
basin, there is a significant proportion of asymptomatic Leishmania (L.) infantum
infected blood donors, who may represent an important threat to transfusion
safety. The Balearic Islands blood bank, located in an area endemic for L.
infantum, carried out a study of donors and patients to investigate the impact of
this infectious disease on blood safety in the region. MATERIALS AND METHODS:
Twenty asymptomatic Leishmania-infected blood donors were followed-up between
2008 and 2011 to investigate the evolution of Leishmania infection in
asymptomatic carriers. Their blood was periodically tested for anti-Leishmania
antibodies by western blot and for Leishmania DNA by quantitative polymerase
chain reaction (qPCR). Additionally, the prevalence of L. infantum infection was
investigated in a group of 68 multiply transfused patients to ascertain the risk
of transfusion-transmitted leishmaniasis (TTL) in the region, taking into account
regular blood component production practices such as pre-storage leucodepletion
and pathogen reduction technology. RESULTS: All 20 donors remained asymptomatic
over the study period (2008-2011). Most donors had repeatedly positive qPCR
results, either persistently or intermittently, but showed no symptoms of
Leishmaniasis. Levels of parasitaemia were remarkably low in asymptomatic donors,
with values <=1 parasite/mL. Despite multiple transfusions received over 15
years, no transfused patient studied was infected with L. infantum. DISCUSSION:
L. infantum-infected donors can remain asymptomatic for at least 3 years. In our
region, no cases of TTL were detected, despite an active search in multiply
transfused patients. This seems to be related to two independent variables: (i) a
low concentration of the parasite in the peripheral blood of asymptomatic
carriers and (ii) the application of methods with proven efficacy against TTL,
such as leucodepletion and pathogen reduction technology.
PMID- 28488963
TI - Towards the implementation of patient blood management across Europe.
PMID- 28488964
TI - Passive haemovigilance of blood components treated with a riboflavin-based
pathogen reduction technology.
PMID- 28488965
TI - Mild-to-moderate foeto-maternal haemorrhage in the third trimester and at term of
pregnancy: quantitative determination and clinical-diagnostic evaluation.
AB - BACKGROUND: Foeto-maternal haemorrhage (FMH), a gestational event that occurs
before or during delivery, consists of a loss of foetal blood into the maternal
circulation. FMH occurs more frequently during the third trimester or labour both
in normal and complicated pregnancies. In the case of alloimmunisation, the
maternal immunological response and the severity of the resulting foetal or
neonatal disease depend on the amount of foetal blood that passes into the
maternal circulation. The aim of this study was to determine FMH in the third
trimester and at term of pregnancy and to evaluate the role of clinical and
ultrasound markers in the prediction of FMH. MATERIALS AND METHODS: FMH was
quantified by cytofluorimetric testing at 28 to 35 weeks of gestation in 223
women and at term in 465 women, all with risk factors. Foetal evaluation included
foetal movement profile, middle cerebral artery peak velocity of systolic blood
flow (MCA-PSV) and cardiotocographic monitoring. RESULTS: All women tested
negative for FMH in the third trimester. Four patients (0.9%) tested positive at
term, with estimated volumes of bleeding of 2.2, 8.1, 12.3 and 39.8 mL. Three FMH
cases (75%) had a non-reassuring cardiotocography compared to 8.9% (42/461) of
women without FMH (p=0.003) and two FMH cases reported a reduction in foetal
movements reduction compared to four of those without FMH (p=0.001). Mean MCA-PSV
was normal in both the groups with and without FMH (p=0.22). DISCUSSION: FMH is
rare in pregnancy and at term. Cytofluorimetric testing is a specific method to
detect mild-to-moderate FMH even when the MCA-PSV is not informative. Mild-to
moderate FMH is significantly associated with reduced foetal movements and non
reassuring cardiotocographic monitoring.
PMID- 28488966
TI - Haemolysis, pure red cell aplasia and red cell antibody formation associated with
major and bidirectional ABO incompatible haematopoietic stem cell
transplantation.
AB - BACKGROUND: Acute and delayed haemolysis, alloimmunisation and pure red cell
aplasia (PRCA) are potential complications after ABO incompatible haematopoietic
stem cell transplantation (HSCT). The aims of this study were to investigate
acute and delayed red blood cell (RBC) antibody-associated complications,
including haemolysis, PRCA and alloimmunisation in major and bidirectional ABO
incompatible HSCT. MATERIALS AND METHODS: We retrospectively examined the
transplant courses of 36 recipients of bone marrow or peripheral blood stem cells
from ABO incompatible donors and evaluated the current practice of performing
plasmapheresis in patients with higher isoagglutinin titres. We investigated the
role of ABO incompatibility in haematopoietic recovery, transfusion requirements,
alloimmunisation and PRCA. RESULTS: Laboratory signs of acute haemolysis were
noted in five (14%) patients, one (3%) of whom had clinically overt haemolysis.
Patients with haemolysis had IgM titres >=1:8 and received >16 mL of RBC in the
HSCT. In patients with higher titres, plasmapheresis performed prior to the
transplant prevented acute haemolysis. Delayed haemolysis was not recorded in the
follow up. Haematopoietic recovery and transfusion requirements did not differ
notably between patients with and without haemolysis. De novo RBC antibodies were
detected in two (5.5%) patients after HSCT, and PRCA was noted in one (3%)
patient. DISCUSSION: Carried out with adequate graft processing, plasmapheresis
and blood component support, haemolysis is not a common complication after HSCT.
Our results confirm that the occurrence of haemolysis depends on larger RBC
volumes and higher isoagglutinin titres. Despite the reduction of patients'
isoagglutinin titres by plasmapheresis, we still noted a critical combination for
the development of laboratory signs of haemolysis (IgM titre >=1:8 and RBC volume
>16 mL). De novo immunisation to RBC antigens and PRCA are rare events following
ABO incompatible HSCT.
PMID- 28488967
TI - Purinergic control of red blood cell metabolism: novel strategies to improve red
cell storage quality.
AB - Transfusion of stored blood is regarded as one of the great advances in modern
medicine. However, during storage in the blood bank, red blood cells (RBCs)
undergo a series of biochemical and biomechanical changes that affect cell
morphology and physiology and potentially impair transfusion safety and efficacy.
Despite reassuring evidence from clinical trials, it is universally accepted that
the storage lesion(s) results in the altered physiology of long-stored RBCs and
helps explain the rapid clearance of up to one-fourth of long-stored RBCs from
the recipient's bloodstream at 24 hours after administration. These
considerations explain the importance of understanding and mitigating the storage
lesion. With the emergence of new technologies that have enabled large-scale and
in-depth screening of the RBC metabolome and proteome, recent studies have
provided novel insights into the molecule-level metabolic changes underpinning
the accumulation of storage lesions to RBCs in the blood bank and alternative
storage strategies to mitigate such lesion(s). These approaches borrow from
recent insights on the biochemistry of RBC adaptation to high altitude hypoxia.
We recently conducted investigations in genetically modified mice and revealed
novel insights into the role of adenosine signalling in response to hypoxia as a
previously unrecognised cascade regulating RBC glucose metabolism and increasing
O2 release, while decreasing inflammation and tissue injuries in animal models.
Here, we will discuss the molecular mechanisms underlying the role of purinergic
molecules, including adenosine and adenosine triphosphate in manipulating RBCs
and blood vessels in response to hypoxia. We will also speculate about new
therapeutic possibilities to improve the quality of stored RBCs and the prognosis
after transfusion.
PMID- 28488968
TI - Prevention of red cell storage lesion: a comparison of five different additive
solutions.
AB - BACKGROUND: In Europe, red cell concentrates (RCC) are usually stored in SAGM
(saline-adenine-glucose-mannitol). During storage, in vitro red cell quality
declines, including lowered energy status and increased cell lysis. Recently,
several additive solutions (ASs), designed to diminish the decline in in vitro
quality during storage, have been developed. These new solutions have mainly been
developed to better maintain red blood cell (RBC) 2,3-biphosphoglycerate (2,3
BPG) levels and energy status during storage. High levels of 2,3 BPG allow for
better oxygen release while high energy status is necessary for function and
survival of RBC in vivo. In a paired study design, RBC ASs were compared for
their ability to provide improved in vitro quality during hypothermic storage.
MATERIALS AND METHODS: For each experiment, 5 whole blood units held overnight
were pooled and split. The whole blood units were processed according to the
buffy coat method. RBCs were resuspended in either SAGM, PAGGSM, PAG3M, E-Sol 5
or AS-7 and leucoreduced by filtration. RCCs were stored for eight weeks at 2-6
degrees C and sampled weekly for analysis of in vitro quality parameters.
RESULTS: Red cell concentrates stored in PAG3M, E-Sol 5 and AS-7 showed
significantly higher lactate production and higher levels of intracellular
adenosine triphosphate (ATP) and total adenylate. 2,3 BPG levels rapidly declined
during storage in SAGM and PAGGSM. The decline in 2,3 BPG was inhibited during
storage in E-Sol 5 and AS-7, while in PAG3M, 2,3 BPG level increased above the
initial level till day 35 and remained detectable till day 56. Haemolysis was
comparable for all ASs until day 35, upon prolonged storage, haemolysis in SAGM
was higher than with the other ASs. As compared to SAGM, storage in PAGGSM,
PAG3M, E-Sol 5 and AS-7 better maintained morphological properties. DISCUSSION:
Storage of RBCs in the new generation ASs yield RBCs with more stable metabolite
levels and improved overall quality during storage as compared with RBCs stored
in SAGM.
PMID- 28488969
TI - A cost analysis of public cord blood banks belonging to the Italian Cord Blood
Network.
AB - BACKGROUND: Public cord blood banking is currently managed in Italy by a network
of 19 regional cord blood banks coordinated by the National Blood Centre and the
National Transplant Centre. A cost analysis was carried out within the Italian
network to determine the relationship between cost of cord blood collection and
banking and size of the bank inventory, which ranged from 106 to 9,341 units on
December 31st, 2012. MATERIALS AND METHODS: The 19 banks were invited to report
costs incurred in 2012 related to cord blood unit collection, transportation,
biological validation, characterisation, manipulation, cryopreservation, storage,
data management, and general costs. Missing information on selected items was
replaced with standardised costs represented by average data obtained from the
reporting banks. Eight banks (52%) participated in the study. Average costs were
determined in the three banks with inventories of >3,000 units vs the three banks
with inventories of <1,000 units. RESULTS: Both cord blood collection and cord
blood banking costs per unit were lower in the larger banks than in the smaller
banks (average collection costs: ? 119.25 and ? 151.31, respectively; average
banking costs: ? 3,614.15 and ? 8,158.37, respectively). DISCUSSION: The study
outlined an inverse relationship between the costs of cord blood collection and
banking and the size of the bank inventory, suggesting that scale economies could
be obtained through centralisation of banking activities.
PMID- 28488970
TI - Is it time to re-think a sustainable banking model for the Italian Cord Blood
Network?
PMID- 28488971
TI - Quality assessment and transfusion efficacy of buffy coat-derived platelet
concentrates washed with platelet additive solution.
AB - BACKGROUND: Transfusion of washed platelet concentrates (W-PC) is recommended for
some patients, such as those who have had previous severe allergic transfusion
reactions. However, we still lack a standardised method for preparing these
products. Here, we assessed the effect of a manual washing procedure on in vitro
platelet quality and on the transfusion efficacy of W-PCs. MATERIALS AND METHODS:
Buffy coat-derived W-PC in Composol solution were prepared by one-step
centrifugation. Platelet activation and function were evaluated before and after
washing by means of: (i) CD62 expression by flow cytometry; (ii) platelet
aggregation (LTA); and (iii) the VerifyNow(r) P2Y12 test. A pilot prospective
transfusion study was carried out in 11 onco-hematology patients receiving, in a
short time, two consecutive transfusions: one with standard PC (S-PC) and one
with W-PC. The post-transfusion platelet increment, the 1 h and 24 h corrected
count increment (CCI) and occurrence of bleeding events were used as indices of
transfusion efficacy. RESULTS: Platelet recovery in W-PC was 84.8+/-5.4%. Washing
slightly increased platelet activation in W-PC vs pre-washed samples (% CD62+
platelets 23.6+/-7 vs 14.8+/-1; p=0.03). As compared to prewash samples, platelet
reactivity of W-PC as measured by VerifyNow(r) P2Y12 was significantly lower with
ADP (PRU 32.2+/-37.7 vs 4.2+/-2.4, p=0.027), but similar using TRAP. Platelet
aggregation responses to TRAP, collagen, ristocetin and arachidonic acid were
maintained in W-PC. The pilot transfusion trial showed similar 1 h (13.5+/-5.6 vs
11.5+/-7.3, p=0.49) and 24 h (11+/-7.2 vs 9+/-6.5, p=0.48) CCI for S-PC and W-PC.
Transfusion of W-PC was not associated with an increased number of bleeding
events. DISCUSSION: We have set up a simple method to obtain buffy-coat-derived W
PC, which has minor effects on in vitro platelet quality and transfusion
effectiveness. This procedure can be easily implemented in transfusion centres
for on-demand preparation of washed platelets.
PMID- 28488972
TI - Clinically relevant non-major bleeding with oral anticoagulants: non-major may
not be trivial.
PMID- 28488973
TI - A pathogen reduction clinical trial in retrospect.
PMID- 28488974
TI - Blood donor deferral policies across Europe and characteristics of men whohave
sex with men screened for human immunodeficiency virus in bloodestablishments:
data from the European Men-who-have-sex-with-men Internet Survey (EMIS).
AB - BACKGROUND: The predominant mode of transmission of human immunodeficiency virus
(HIV) in Europe is male-to-male transmission. Men who have sex with men (MSM) are
deferred from donating blood in many countries, but nevertheless do donate blood.
Based on data from 34 countries, we estimated the proportion of MSM screened for
HIV in the context of a blood donation and identified individual factors
associated with this HIV screening in order to propose possible public health
interventions. MATERIALS AND METHODS: In 2010, the first European MSM Internet
Survey (EMIS) collected self-reported data on HIV testing from >180,000 MSM in 38
European countries. Using logistic regression, demographic and behavioural
factors associated with screening for HIV in blood establishments were
identified. Stratified by European sub-region, we analysed the proportion of MSM
screening in blood establishments by time elapsed since last negative HIV test.
RESULTS: Donor eligibility criteria for MSM vary across Europe with most
countries using permanent deferral. The Western region had the lowest (2%)
proportion of MSM screened in blood establishments and the Northeastern region
had the highest (14%). Being <25 years old, not disclosing sexual attraction to
men, never having had anal intercourse with a man, having a female partner,
living in a rural area, and certain European sub-regions or countries of
residence increased the likelihood of being screened in blood establishments.
DISCUSSION: In spite of deferral policies, MSM are screened for HIV in the
context of blood donations. Gay-friendly testing services are rare in rural
areas, and young men might be reluctant to disclose their sexual orientation.
Recent developments, such as home sampling, might offer new testing possibilities
for those not reached by established services yet wishing to know their HIV
status. Donor selection procedures should be improved. Both interventions might
help to further reduce the risk of transfusion-transmitted infections.
PMID- 28488975
TI - The Italian Regulatory Guidelines for the implementation of Patient Blood
Management.
PMID- 28488976
TI - Haemophilia A: the consequences of de novo mutations. Two case reports.
PMID- 28488977
TI - Non-invasive foetal RhD genotyping to guide anti-D prophylaxis: an external
quality assurance workshop.
PMID- 28488978
TI - Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis and Treatment With a
Biologic: A Case Report.
AB - INTRODUCTION: One of the most dangerous dermatologic emergencies is Stevens
Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN). Although a rare disease,
it can often lead to significant mortality. CASE PRESENTATION: In this case
report, we present a 77-year-old man who developed a sloughing rash that was
secondary to a nonsteroidal anti-inflammatory drug. In addition to the
recommended supportive care, the patient was treated with etanercept, a new, less
commonly used intervention. DISCUSSION: We provide a brief review of SJS/TEN.
Nonsteroidal anti-inflammatory drugs are a rare cause of SJS/TEN, and
additionally, the use of biologics is a novel treatment modality for SJS/TEN.
PMID- 28488979
TI - An Unlikely Rapid Transformation of Myelodysplastic Syndrome to Acute Leukemia: A
Case Report.
AB - INTRODUCTION: Myelodysplastic syndrome is characterized by stem-cell-derived
clonal myelopoiesis with an alteration in proliferation and differentiation. This
condition carries a potential for transformation to acute leukemia, primarily in
cases that are accompanied by high-risk features at diagnosis. CASE PRESENTATION:
A 68-year-old man with recently diagnosed myelodysplastic syndrome and Sweet
syndrome (acute febrile neutrophilic dermatosis) presented to our Emergency
Department with shortness of breath. During his hospital course, he developed
signs and symptoms, predominantly consisting of respiratory difficulties, that
were not typically characteristic of transformation to acute leukemia. Several
days into his hospitalization, it was determined that the patient's underlying
hematologic process seemed to have rapidly evolved into an acute myeloid
leukemia, which accounted for the progression of symptoms. This patient
ultimately opted for comfort measures only and died shortly thereafter.
DISCUSSION: Two important factors stood out as representing an atypical
presentation. First, this patient lacked any of the high-risk features of
myelodysplastic syndrome that typically portend transformation. In addition, his
progression to acute leukemia in 28 days from the time of diagnosis was far more
rapid than the 274-day median previously described in the literature. We theorize
that the presence of Sweet syndrome may have served as a predisposing factor to
transformation. This finding may offer benefit to physicians to potentially
better predict this outcome and pursue more aggressive treatment measures earlier
in the course of the disease in such a setting.
PMID- 28488980
TI - Response to Functional Medicine Case Study and Editorial.
PMID- 28488981
TI - A Survey of Parents with Children on the Autism Spectrum: Experience with
Services and Treatments.
AB - INTRODUCTION: Autism spectrum disorders (ASD) are lifelong neurodevelopmental
disorders, and little is known about how parents address the health and
psychosocial consequences of ASD. Few studies have examined use of various
treatments and services in a large, diverse sample of children with ASD and their
families. OBJECTIVE: This paper presents methods to create an autism research
resource across multiple large health delivery systems and describes services and
treatments used by children with ASD and their families. METHODS: Four study
sites conducted a Web survey of parents of children and adolescents with ASD who
were members of Kaiser Permanente. We tabulated data distributions of survey
responses and calculated chi2 statistics for differences between responders and
nonresponders. RESULTS: The children of the 1155 respondents were racially and
ethnically diverse (55% white, 6% black, 5% Asian, 9% multiracial, 24% Hispanic)
and representative of the total population invited to participate with respect to
child sex (83% male), child age (57% < 10 years), and ASD diagnosis (64% autistic
disorder). The most frequently used services and treatments were Individualized
Education Programs (85%), family physician visits (78%), and occupational and
speech therapy (55% and 60%, respectively). Home-based programs frequently
included implementation of social skills training (44%) and behavior management
(42%). Prescription medication use was high (48%). Caregivers reported disruption
of personal and family routines because of problem behaviors. CONCLUSION: These
survey data help to elucidate parents' experiences with health services for their
children with ASD and serve as a potential resource for future research.
PMID- 28488982
TI - Philanthropy and Beyond: Creating Shared Value to Promote Well-Being for
Individuals in Their Communities.
AB - Health care organizations can magnify the impact of their community service and
other philanthropic activities by implementing programs that create shared value.
By definition, shared value is created when an initiative generates benefit for
the sponsoring organization while also generating societal and community benefit.
Because the programs generate benefit for the sponsoring organizations, the
magnitude of any particular initiative is limited only by the market for the
benefit and not the resources that are available for philanthropy.In this article
we use three initiatives in sectors other than health care to illustrate the
concept of shared value. We also present examples of five types of shared value
programs that are sponsored by health care organizations: telehealth, worksite
health promotion, school-based health centers, green and healthy housing, and
clean and green health services. On the basis of the innovativeness of health
care organizations that have already implemented programs that create shared
value, we conclude that the opportunities for all health care organizations to
create positive impact for individuals and communities through similar programs
is large, and the limits have yet to be defined.
PMID- 28488983
TI - Effectiveness of Electrostimulation on Whole Salivary Flow Among Patients with
Type 2 Diabetes Mellitus.
AB - CONTEXT: Xerostomia and hyposalivation are associated with diabetes. Research is
sparse regarding electrostimulation as a mainstream therapy for salivary gland
hypofunction. OBJECTIVE: To clinically evaluate the effectiveness of
transcutaneous electric nerve stimulation (TENS) therapy in stimulating whole
salivary flow among patients with xerostomia and hyposalivation caused by
diabetes mellitus. DESIGN: Forty patients between age 30 to 75 years with
diabetes mellitus categorized as controlled or uncontrolled who had subjective
symptoms of xerostomia and an objective sign of hyposalivation were included in a
prospective study. MAIN OUTCOME MEASURES: Unstimulated saliva through the "low
forced spitting" method and stimulated saliva collection using TENS were assessed
and compared. Longer-term effects of TENS application were evaluated by recalling
the patient 24 hours later. RESULTS: A statistically significant increase in
stimulated whole saliva after TENS application in continuous mode (p < 0.001) was
demonstrated compared with unstimulated saliva, especially in xerostomic patients
with diabetes. Burst mode inferred a statistically significant decrease in
salivary flow (p < 0.001). CONCLUSION: In patients with diabetes with xerostomia
and hyposalivation, TENS was highly effective in stimulating whole salivary flow.
PMID- 28488984
TI - Research Letter: Anticholinergic Drugs and the Gallbladder -A Neglected Effect?
PMID- 28488985
TI - An Alternative Paradigm for Evidence-Based Medicine: Revisiting Lawrence Weed,
MD's Systems Approach.
AB - Lawrence Weed, MD, is renowned for being the father of the Problem-Oriented
Medical Record (POMR), the medical care standard for collecting, managing, and
contextualizing patient data in medical records. What have been consistently
overlooked are his teachings on knowledge coupling, which refers to matching
patient data with associated medical knowledge. Together, the POMR standard and
knowledge coupling are meant to form the basis of a systems approach that enables
individualized evidence-based decision making within the context of
multimorbidity and patient complexity.The POMR and knowledge coupling tools
operationalize a problem-oriented model that reflects a sophisticated general
systems theoretical approach to knowledge. This paradigm transcends reductionist
approaches to knowledge by depicting how the meaning of specific entities (eg,
disease constructs) and their associated probabilities can only be understood
within their respective spatiotemporal and biopsychosocial relational contexts.
Rigorous POMRs therefore require knowledge inputs from a network of
interconnections among specific entities, which Dr Weed enabled through
development of the Knowledge Net standard. The Knowledge Net's relational
structure determines the applicability of knowledge within specific patient
contexts. To enable the linkage of unique combinations of data in individual
patient POMRs with existing medical knowledge structured in Knowledge Nets, Dr
Weed developed the Knowledge Coupling standard.Dr Weed's standards for record
keeping and knowledge coupling form the basis of a combinatorial approach to
evidence-based medicine that fulfills Stange's call for a science of
connectedness. Ensuing individualized processes of care become the dynamo
powering a learning health care system that enables a co-construction of health
premised on empowerment and intelligent human decision making, rather than
promoting the artificial intelligence of tools. If the value of Engel's
biopsychosocial model indeed relates to "guiding the parsimonious application of
medical knowledge to the needs of each patient," Dr Weed's approach warrants
serious consideration.
PMID- 28488986
TI - Effect of a Smoking Cessation Program on Sexual Function Recovery Following
Robotic Prostatectomy at Kaiser Permanente Southern California.
AB - INTRODUCTION: The association between cigarette smoking and erectile dysfunction
has been well established. Studies demonstrate improvements in erectile rigidity
and tumescence as a result of smoking cessation. Radical prostatectomy is also
associated with worsening of erectile function secondary to damage to the
neurovascular bundles. To our knowledge, no previous studies have examined the
relationship between smoking cessation after prostate cancer diagnosis and its
effect on sexual function following robotic prostatectomy. We sought to
demonstrate the utility of a smoking cessation program among patients with
prostate cancer who planned to undergo robotic prostatectomy at Kaiser Permanente
Southern California. METHODS: All patients who underwent robotic prostatectomy
between March 2011 and April 2013 with known smoking status were included, and
were followed-up through November 2014. All smokers were offered the smoking
cessation program, which included wellness coaching, tobacco cessation classes,
and pharmacotherapy. Patients completed the Expanded Prostate Cancer Index
Composite-26 (EPIC-26) health-related quality-of-life (HR-QOL) survey at baseline
and postoperatively at 1, 3, 6, 12, 18, and 24 months. There were 2 groups based
on smoking status: Continued smoking vs quitting group. Patient's age, Charlson
Comorbidity Score, body mass index, educational level, median household income,
family history of prostate cancer, race/ethnicity, language, nerve-sparing
status, and preoperative/postoperative clinicopathology and EPIC-26 HR-QOL scores
were examined. A linear regression model was used to predict sexual function
recovery. RESULTS: A total of 139 patients identified as smokers underwent the
smoking cessation program and completed the EPIC-26 surveys. Fifty-six patients
quit smoking, whereas 83 remained smokers at last follow-up. All demographics and
clinicopathology were matched between the 2 cohorts. Smoking cessation, along
with bilateral nerve-sparing status, were the only 2 modifiable factors
associated with improved sexual function after prostatectomy (6.57 points, p =
0.0226 and 8.97 points, p = 0.0485, respectively). CONCLUSION: In the setting of
robotic prostatectomy, perioperative smoking cessation is associated with a
significant improvement in long-term sexual functional outcome when other factors
are adjusted.
PMID- 28488987
TI - From the Bedside: A Family Physician Experiences Health Care from the Patient
Side.
PMID- 28488988
TI - Are They Too Old for Surgery? Safety of Cholecystectomy in Superelderly Patients
(>= Age 90).
AB - CONTEXT: Cholecystectomy is the most common general surgery procedure in patients
older than age 65 years. By 2050, it is estimated that 2.0% of the population
will be older than age 90 years. OBJECTIVE: To assess the mortality of
cholecystectomy in superelderly patients (>= age 90 years). DESIGN: Using the
American College of Surgeons National Surgical Quality Improvement Program
database, a retrospective analysis was performed of superelderly patients who
underwent laparoscopic and open cholecystectomy between 2005 and 2012. MAIN
OUTCOME MEASURES: Thirty-day mortality. RESULTS: A total of 1007
cholecystectomies were performed in superelderly patients between 2005 and 2012.
Of these surgical procedures, 807 (80%) were nonemergent and 200 (20%) were
performed emergently. Two hundred sixteen procedures (21.4%) were open and 791
(78.6%) were laparoscopic. Mortality did not decrease significantly during the
study period. The overall mortality was 5.5%, significantly less for the
laparoscopic group (3.7% vs 12%, p < 0.001) and for the nonemergent group (4.5%
vs 9.5%, p < 0.005). The median length of stay for open cholecystectomy was 9
days compared with 5 days for laparoscopic (p < 0.001); for nonemergent
cholecystectomy it was 5 days compared with 7 days for emergent cholecystectomy
(p < 0.001). CONCLUSION: The mortality after cholecystectomy in superelderly
patients did not change significantly during the study period. The mortality and
morbidity for laparoscopic and elective procedures were significantly lower than
for open procedures and for emergent procedures, respectively.
PMID- 28488989
TI - Spice-y Kidney Failure: A Case Report and Systematic Review of Acute Kidney
Injury Attributable to the Use of Synthetic Cannabis.
AB - INTRODUCTION: Spice is a synthetic cannabinoid that is readily available for
purchase in smoke shops at relatively low cost. Spice is not detectable upon
routine drug screening, making it an increasingly popular new street drug. CASE
REPORT: A 21-year-old man presented with new-onset seizures. During the next 2
days, he developed uncontrollable hypertension, agitation, respiratory failure
requiring intubation, pulmonary hypertension, and acute kidney injury (AKI) with
a maximum blood urea nitrogen/creatinine level of 54/7.90 mg/dL. A complete renal
workup was negative, but his urine sediment revealed granular casts. A discussion
with family and friends revealed that this patient had smoked Spice during the
last month. His renal function started to improve with supportive therapy, and
his AKI resolved by the time of discharge without renal replacement therapy.
DISCUSSION: Spice differs from marijuana because it is a cannabinoid receptor
type 1 and 2 agonist. The pathologic mechanism of AKI remains unclear, but the
condition likely is attributable to acute tubular necrosis or acute interstitial
nephritis, as proven by biopsies performed in previous case series. It is
important to raise awareness that a new Spice strain that may be circulating in
the Southern California Inland Empire can endanger young users who may develop
seizures, respiratory failure, and AKI.
PMID- 28488990
TI - Patient and Practitioner Perspectives on Culturally Centered Integrated Care to
Address Health Disparities in Primary Care.
AB - INTRODUCTION: Addressing the multifaceted health and mental health needs of
ethnically and culturally diverse individuals is a challenge within the current
health care system. Integrated care provides a promising approach to improve
mental health treatment-seeking disparities; however, adaptation of care models
to impact African Americans is lacking. Although resources to support engagement
of diverse populations in depression care exist, little has been developed to
tailor patient preferences in accessing and engaging mental health services that
are integrated into primary care. OBJECTIVE: Our research seeks to add a cultural
focus to the existing literature concerning integrated health care models to help
address depression and selected co-occurring chronic health conditions in primary
care settings. METHODS: Thirty-two adult patients of an integrated primary care
clinic participated in focus groups discussing their individual health
experiences. Nine health care practitioners/administrators from five different
integrated practice settings in the Atlanta, GA, area participated in key
informant interviews. MAIN OUTCOME MEASURES: Transcripts were analyzed for key
themes related to depression care, perceived unmet cultural needs, and desired
adaptations. RESULTS: Common themes emerged such as the importance of peer
support and community engagement as areas of patient interest. Participants had
good knowledge in recognizing depressive symptoms but were less knowledgeable
about treatment options and expectations of treatment. The administrative and
practitioner perspective suggests that patient preferences are valued and
perceived as valid. CONCLUSION: It is critical that strategies and models are
developed to improve health care among underserved minorities because current
models offer variable efficacy among this population.
PMID- 28488991
TI - Geriatric Hip Fracture Care: Fixing a Fragmented System.
AB - CONTEXT: Fragmentation in geriatric hip fracture care is a growing concern
because of the aging population. Patients with hip fractures at our institution
historically were admitted to multiple different services and units, leading to
unnecessary variation in inpatient care. Such inconsistency contributed to delays
in surgery, discharge, and functional recovery; hospital-acquired complications;
failure to adhere to best practices in osteoporosis management; and poor
coordination with outpatient practitioners. OBJECTIVE: To describe a stepwise
approach to systems redesign for this patient population. DESIGN: We designed and
implemented a comprehensive geriatric hip fracture program for patients aged 65
years and older at our academic Medical Center in October 2014. Key interventions
included admission of all ward-status patients to the Orthopedics Service with
hospitalist comanagement; geographic placement on the Orthopedics Unit; and
standardized, evidence-based electronic order sets bundling geriatric best
practices and a streamlined workflow for discharge planning. MAIN OUTCOME
MEASURES: Hospital length of stay. RESULTS: We identified 271 admissions among
267 patients between January 1, 2012, and March 31, 2016; of those, 154 were
before and 117 were after program implementation. Mean hospital length of stay
significantly improved from 6.4 to 5.5 days (p = 0.004). The 30-day all-cause
readmission rate and discharge disposition remained stable. The percentage of
patients receiving osteoporosis evaluation and treatment increased significantly.
The rate of completed 30-day outpatient follow-up also improved. CONCLUSION: Our
comprehensive geriatric hip fracture program achieved and sustained gains in the
quality and efficiency of care by improving fragmentation in the health care
system.
PMID- 28488992
TI - Image Diagnosis: Splenic Infarction Associated with Oral Contraceptive Pills in a
Healthy Young Woman.
PMID- 28488993
TI - Physician Guide to Appropriate Opioid Prescribing for Noncancer Pain.
AB - Prescription opioid use for relief of noncancer pain has risen dramatically in
the last 15 years, contributing to a quadrupling of opioid overdoses and
prescription opioid-related deaths. This crisis is resulting in heightened
attention by health care professionals and organizations, law enforcement, and
the government. In this article, I highlight key topics in the management of
patients using opioids (or potentially needing opioids) in outpatient clinical
practice; federal and state law enforcement actions regarding physicians' illegal
prescribing of opioids; multimodal approaches to pain control; nonmedication
management of pain; response strategies when suspecting a patient of diverting or
misusing opioids; and warning signs for abuse or diversion. For those patients
for whom opioids are appropriate, I describe key elements for prescribing,
including documentation of a detailed history and examination, appropriate
evaluation to arrive at a specific diagnosis, individualizing management, and
ongoing monitoring (including the use of urine drug screening and a prescription
drug monitoring program). In addition to individual action, when possible, the
initiation of systemwide and clinicwide safe prescribing practices supports the
physician and patient such that the patient's well-being is at the heart of all
pain management decisions. Physicians are encouraged to further educate
themselves to treat pain safely and effectively; to screen patients for opioid
use disorder and, when diagnosed, to connect them with evidence-based treatment;
and to follow Centers for Disease Control and Prevention guidelines whenever
possible.
PMID- 28488994
TI - Establishing and maintaining the National Vaccination Register in Finland.
AB - Computerised, population-based vaccination registers are valuable tools for
assessing the vaccine uptake and impact in populations. However, reliable impact
assessment is only possible if the data quality can be reviewed and monitored
continuously. This report describes the establishment and maintenance of the
National Vaccination Register (NVR) in Finland. Currently, the NVR covers
nationwide records of vaccinations given within the frame of the National
Vaccination Programme since 2009. All vaccinations registered in the NVR contain
a record of the personal identity code, the administered vaccine, and the date of
vaccination. The vaccine lot number is the key component for recording and
identifying vaccinations, because of its broad availability across patient
information systems and its importance in vaccine safety monitoring. Vaccination
records are accumulated and updated daily into the NVR, and their completeness is
monitored monthly to assess deficiencies in data entry and data collection.
Additionally, an alert system reports unexpected changes in data accumulation
prompting the validation of observed changes in vaccination coverage. The
presented process documentation may serve as basis to improve the design and
quality of other vaccination or healthcare registers and aims to inspire the set
up of vaccination registers in those countries which still do not have one.
PMID- 28488995
TI - Written reminders increase vaccine coverage in Danish children - evaluation of a
nationwide intervention using The Danish Vaccination Register, 2014 to 2015.
AB - We evaluated a national intervention of sending written reminders to parents of
children lacking childhood vaccinations, using the Danish Vaccination Register
(DDV). The intervention cohort included the full birth cohort of 124,189 children
born in Denmark who reached the age of 2 and 6.5 years from 15 May 2014 to 14 May
2015. The reference cohort comprised 124,427 children who reached the age of 2
and 6.5 years from 15 May 2013 to 14 May 2014. Vaccination coverage was higher in
the intervention cohort at 2.5 and 7 years of age. The differences were most
pronounced for the second dose of the measles-mumps-rubella vaccine (MMR2) and
the diphtheria-tetanus-pertussis-polio vaccine DTaP-IPV4 among the 7-year-olds,
with 5.0 percentage points (95% confidence interval (CI): 4.5-5.4) and 6.4
percentage points (95% CI: 6.0-6.9), respectively. Among the 2.5 and 7-year-olds,
the proportion of vaccinations in the preceding 6 months was 46% and three times
higher, respectively, in the intervention cohort than the reference cohort. This
study indicates a marked effect of personalised written reminders, highest for
the vaccines given later in the schedule in the older cohort. In addition, the
reminders increased awareness about correct registration of vaccinations in DDV.
PMID- 28488996
TI - Assessing varicella vaccine effectiveness and its influencing factors using
health insurance claims data, Germany, 2006 to 2015.
AB - In Germany, routine childhood varicella vaccination was implemented in 2004 with
two doses recommended since 2009. We used an immunisation information system
based on countrywide health insurance claims data to analyse vaccine
effectiveness (VE) and factors influencing VE. We applied proportional hazard
models to estimate VE under various conditions and compared the risk of acquiring
varicella among unvaccinated children in regions with high vs low vaccination
coverage (VC). Among 1.4 million children we identified 29,404 varicella cases
over a maximum follow-up of 8 years post-vaccination. One-dose VE was 81.9% (95%
confidence interval (CI): 81.4-82.5), two-dose VE 94.4% (95% CI: 94.2-94.6). With
dose one given 1-27 days after measles-containing vaccine (MCV), one-dose VE was
32.2% (95% CI: 10.4-48.6), two-dose VE 92.8% (95% CI: 84.8-96.6). VE was not
associated with age at vaccination (11-14 vs >= 15 months), time since
vaccination, or vaccine type. Unvaccinated children had a twofold higher risk of
acquiring varicella in low VC regions. Our system generated valuable data,
showing that two-dose varicella vaccination provides good protection for at least
8 years. Unvaccinated children benefit from herd effects. When the first
varicella vaccine dose is given shortly after MCV, a second dose is essential.
PMID- 28488997
TI - Registries: An essential tool for maximising the health benefits of immunisation
in the 21st century.
PMID- 28488998
TI - Ongoing measles outbreak in Wallonia, Belgium, December 2016 to March 2017:
characteristics and challenges.
AB - We describe characteristics of an ongoing measles outbreak in Wallonia, Belgium,
and difficulties in control measures implementation. As at 12 March 2017, 177
measles cases were notified, of which 50% were 15 years and older, 49% female.
Atypical clinical presentation and severe complications, mainly among adults, in
combination with late notification, low or unknown vaccination coverage of
contacts, infected healthcare workers and increased workload due to contact
tracing, are the main concerns for outbreak management.
PMID- 28488999
TI - Immunisation Information Systems - useful tools for monitoring vaccination
programmes in EU/EEA countries, 2016.
AB - Immunisation Information Systems (IIS) are computerised confidential population
based-systems containing individual-level information on vaccines received in a
given area. They benefit individuals directly by ensuring vaccination according
to the schedule and they provide information to vaccine providers and public
health authorities responsible for the delivery and monitoring of an immunisation
programme. In 2016, the European Centre for Disease Prevention and Control (ECDC)
conducted a survey on the level of implementation and functionalities of IIS in
30 European Union/European Economic Area (EU/EEA) countries. It explored the
governance and financial support for the systems, IIS software, system
characteristics in terms of population, identification of immunisation
recipients, vaccinations received, and integration with other health record
systems, the use of the systems for surveillance and programme management as well
as the challenges involved with implementation. The survey was answered by 27 of
the 30 EU/EEA countries having either a system in production at national or
subnational levels (n = 16), or being piloted (n = 5) or with plans for setting
up a system in the future (n = 6). The results demonstrate the added-value of IIS
in a number of areas of vaccination programme monitoring such as monitoring
vaccine coverage at local geographical levels, linking individual immunisation
history with health outcome data for safety investigations, monitoring vaccine
effectiveness and failures and as an educational tool for both vaccine providers
and vaccine recipients. IIS represent a significant way forward for life-long
vaccination programme monitoring.
PMID- 28489000
TI - Suboptimal MMR2 vaccine coverage in six counties in Norway detected through the
national immunisation registry, April 2014 to April 2017.
AB - In 2014, Norway became aware of potential low vaccination coverage for the second
dose of measles-mumps-rubella vaccine (MMR2) in six of 19 counties. This was
detected by comparing the national coverage (NC) for 16-year-olds extracted from
the national immunisation registry SYSVAK with the annual status update for
elimination of measles and rubella (ASU) reported to the World Health
Organization (WHO). The existing method for calculating NC in 2014 did not show
MMR2 coverage. ASU reporting on MMR2 was significantly lower then the NC and
below the WHO-recommended 95% coverage. SYSVAK is based on the Norwegian personal
identification numbers, which allows monitoring of vaccinations at aggregateded
as well as individual level. It is an important tool for active surveillance of
the performance of the Norwegian Childhood Immunisation Programme (NCIP). The
method for calculating NC was improved in 2015 to reflect MMR2 coverage for 16
year-olds. As a result, Norway has improved its real-time surveillance and
monitoring of the actual MMR2 coverage also through SYSVAK (the annual
publication of NC). Vaccinators receive feedback for follow-up if 15-year-olds
are missing MMR2. In 2017, only three counties had an MMR2 coverage below 90%.
PMID- 28489001
TI - Noradrenaline blockade specifically enhances metacognitive performance.
AB - Impairments in metacognition, the ability to accurately report one's performance,
are common in patients with psychiatric disorders, where a putative
neuromodulatory dysregulation provides the rationale for pharmacological
interventions. Previously, we have shown how unexpected arousal modulates
metacognition (Allen et al., 2016). Here, we report a double-blind, placebo
controlled, study that examined specific effects of noradrenaline and dopamine on
both metacognition and perceptual decision making. Signal theoretic analysis of a
global motion discrimination task with adaptive performance staircasing revealed
that noradrenergic blockade (40 mg propranolol) significantly increased
metacognitive performance (type-II area under the curve, AUROC2), but had no
impact on perceptual decision making performance. Blockade of dopamine D2/3
receptors (400 mg amisulpride) had no effect on either metacognition or
perceptual decision making. Our study is the first to show a pharmacological
enhancement of metacognitive performance, in the absence of any effect on
perceptual decision making. This enhancement points to a regulatory role for
noradrenergic neurotransmission in perceptual metacognition.
PMID- 28489002
TI - USP5/Leon deubiquitinase confines postsynaptic growth by maintaining ubiquitin
homeostasis through Ubiquilin.
AB - Synapse formation and growth are tightly controlled processes. How synaptic
growth is terminated after reaching proper size remains unclear. Here, we show
that Leon, the Drosophila USP5 deubiquitinase, controls postsynaptic growth. In
leon mutants, postsynaptic specializations of neuromuscular junctions are
dramatically expanded, including the subsynaptic reticulum, the postsynaptic
density, and the glutamate receptor cluster. Expansion of these postsynaptic
features is caused by a disruption of ubiquitin homeostasis with accumulation of
free ubiquitin chains and ubiquitinated substrates in the leon mutant.
Accumulation of Ubiquilin (Ubqn), the ubiquitin receptor whose human homolog
ubiquilin 2 is associated with familial amyotrophic lateral sclerosis, also
contributes to defects in postsynaptic growth and ubiquitin homeostasis.
Importantly, accumulations of postsynaptic proteins cause different aspects of
postsynaptic overgrowth in leon mutants. Thus, the deubiquitinase Leon maintains
ubiquitin homeostasis and proper Ubqn levels, preventing postsynaptic proteins
from accumulation to confine postsynaptic growth.
PMID- 28489003
TI - Odor identity coding by distributed ensembles of neurons in the mouse olfactory
cortex.
AB - Olfactory perception and behaviors critically depend on the ability to identify
an odor across a wide range of concentrations. Here, we use calcium imaging to
determine how odor identity is encoded in olfactory cortex. We find that, despite
considerable trial-to-trial variability, odor identity can accurately be decoded
from ensembles of co-active neurons that are distributed across piriform cortex
without any apparent spatial organization. However, piriform response patterns
change substantially over a 100-fold change in odor concentration, apparently
degrading the population representation of odor identity. We show that this
problem can be resolved by decoding odor identity from a subpopulation of
concentration-invariant piriform neurons. These concentration-invariant neurons
are overrepresented in piriform cortex but not in olfactory bulb mitral and
tufted cells. We therefore propose that distinct perceptual features of odors are
encoded in independent subnetworks of neurons in the olfactory cortex.
PMID- 28489005
TI - [Long-term efficacy in clinical gene therapy[Editorial]].
PMID- 28489006
TI - [TAVI: Advancements in treatment in Iceland and worldwide[Editorial]].
PMID- 28489007
TI - [Frequency of symptoms and drug treatment among dying patients in the last 24
hours of life at Landspitali - The National University Hospital of Iceland and in
nursing homes].
AB - INTRODUCTION: The purpose of this study was to evaluate the frequency of 5 common
symptoms and drug treatments prescribed and given in the last 24 hours of life in
11 medical units at Landspitali National University Hospital of Iceland (LUH) and
in 7 nursing homes (NH). MATERIAL AND METHODS: Data was collected retrospectively
from 232 charts of patients who died in 2012, using documentation in the
Liverpool Care Pathway (LCP) and the medication management system. RESULTS: About
half of the patients died at LUH with similar gender ratio but 70% of patients in
NH were women. The LCP was used for 50% of all deaths at LUH and 58% in NH. In
45% of all deaths LCP was used for 24 hours or less. The most common symptoms
were pain (51%), agitation (36%) and respiratory tract secretions (36%).
Frequency of symptoms was similar between institutions and age groups. Cancer
patients had significantly higher incidence of agitation and were prescribed and
given higher doses of morphine compared to other groups. Regular medication for
agitation was haloperidol (45%), diazepam (40%) and midazolam (5%). Close to 70%
of the patients were treated with a scopolamin patch for death rattle.
CONCLUSION: A large number of patients have symptoms in the last 24 hours of life
both in hospital and in nursing homes. Symptom control can be improved by
adjusting morphine doses to patients need, using regular doses of benzodiazepine
for agitation and better use of anticholinergic medication for death rattle. Key
words: symptoms, medication, dying patients, last 24 hours of life, hospital,
nursing homes. Correspondence: Svandis Iris Halfdanardottir,
svaniris@landspitali.is.
PMID- 28489004
TI - Analogous mechanism regulating formation of neocortical basal radial glia and
cerebellar Bergmann glia.
AB - Neocortical basal radial glia (bRG) and cerebellar Bergmann glia (BG) are basal
progenitors derived from ventricular apical radial glia (aRG) that selectively
lose their apical processes. bRG and BG have been implicated in the expansion and
folding of the cerebrum and cerebellum, respectively. Here, we analyzed the
molecular characteristics and development of bRG and BG. Transcriptomic
comparison revealed striking similarity of the molecular features of bRG and BG.
We found that heightened ERK signaling activity in aRG is tightly linked to the
temporal formation and the relative abundance of bRG in human and mouse cortices.
Forced activation of an FGF-ERK-ETV axis that is crucial to BG induction
specifically induced bRG with canonical human bRG features in mice. Therefore,
our data point to a common mechanism of bRG and BG generation, bearing
implications to the role for these basal progenitors in the evolution of cortical
folding of the cerebrum and cerebellum.
PMID- 28489008
TI - [Do opioids, sedatives and proton-pump inhibitors increase the risk of
fractures?]
AB - INTRODUCTION: A pharmacoepidemiological study was conducted to analyse the
relationship between bone fracture and the use of certain drugs.
MATERIAL/METHODS: The study includes patients 40 years and older, diagnosed with
bone fractures in the Emergency Department of Landspitali University Hospital in
Reykjavik, Iceland, during a 10-year period (2002-2011). Also were included those
who picked up from a pharmacy 90 DDD or more per year of the drugs included in
the study in the capital region of Iceland during same period. Opiates,
benzodiazepines/hypnotics (sedatives) were compared with HMG-CoA reductase
inhibitors (statins), non-steroid anti-inflammatory drugs (NSAID) and beta
blockers. Proton-pump inhibitors (PPI) and histamine H2-antagonists were also
examined. To examine the association between above drugs and fractures the data
from electronic hospital database were matched to the prescription database run
by the Directorate of Health. RESULTS: A total of 29,056 fractures in 22,891
individuals were identified. The females with fractures were significantly older
and twice as many, compared to males. The odds ratio (OR) for fractures was not
significantly different between the NSAID, statins and beta blockers. OR for
opiates showed almost double increased risk of fractures, 40% increased risk for
sedatives and 30% increased risk for PPIs compared to beta blockers. No increased
fracture-risk was noted in patients taking H2 antagonists. CONCLUSION: This study
shows a relationship between the use of opiates, sedatives and bone fractures.
The incidence of fractures was also increased in patients taking PPIs which is
interesting in the light of the wide-spread use of PPIs in the community. Key
words: Opiates, sedatives, proton- pump inhibitors, fractures. Correspondence:
Magnus Johannsson, magjoh@hi.is.
PMID- 28489009
TI - [Vanishing lungs - a case report].
AB - A 55 year old female with rheumatoid arthritis who was repeatedly admitted to
internal medicine for fever, shortness of breath and pleuritic chest pain.
Laboratory work up showed normal WBC but elevated CRP and sedimentatation rate.
Cultures were negative. Imaging studies revealed elevated diaphragms, bilateral
atelectasis and pleural fluid but normal lung parenchyma. Lung function testing
showed restriction. Anti-dsDNA and anti-Ro/SSA were elevated. A clinical
diagnosis of anti-TNF-induced lupus secondary to infliximab and shrinking lung
syndrome was made. The patient showed improvement on steroids but subsequent
worsening when tapered. Rituximab was then initiated with good results. Key
words: rheumatoid arthritis, infliximab, restrictive lung disease, shrinking lung
syndrome, anti-TNF induced lupus. Correspondence: Thorunn Halldora Thordardottir,
thorhtho@landspitali.is.
PMID- 28489010
TI - [New government, new health policy?[Editorial]].
PMID- 28489011
TI - [The Icelandic organ donation law: has the time arrived for presumed
consent?[Editorial]].
PMID- 28489012
TI - [Icelanders' beliefs about medicines. Use of BMQ].
AB - OBJECTIVE: To study beliefs held by the general public in Iceland about
medicines. METHODS: The Beliefs about Medicines Questionnaire was used to explore
Icelanders' beliefs about medicines. A sample of 1500 Icelandic citizens, aged 18
75, obtained from the Social Science Research Insti-tute was given The Beliefs
about Medicines Questionnaire. RESULTS: The response rate was 61.6%. Most
Icelanders have positive beliefs about their medication as well as general trust.
Those who suffer from chronic diseases are more positive towards medicines than
others and less inclined to view them as excessively used and harmful. Higher
level of education predicts more positive beliefs towards medication - and vice
versa. Gender and age do not seem to affect such beliefs. CONCLUSION: Gaining a
better understanding of people's beliefs about medicines and what determines
these beliefs can be of considerable value in the search for ways to improve
therapy and adherence, espe-cially for those suffering from chronic diseases.
Promoting education for the general public about medicines might result in less
mis-understanding among patients and subsequently better grounded -beliefs and
more adequate therapeutic adherence. Key words: beliefs, medicines, Icelanders,
BMQ, survey. Correspondence: Hlif Vilhelmsdottir, hlif84@gmail.com.
PMID- 28489014
TI - [Surgical treatment for endocarditis in Iceland 1997-2003].
AB - INTRODUCTION: The aim of this study was to evaluate the outcomes of operations
for endocarditis in Iceland, but such results have not been reported before.
MATERIALS AND METHODS: Retrospective nation-wide study of pa--tients that
underwent open-heart surgery for infective endocarditis at Landspitali University
Hospital in 1997-2013. Variables were collected from hospital charts. Long-term
survival was analysed using Kaplan- Meier methods. Mean follow-up time was 7.2
years. RESULTS: Out of 179 patients diagnosed with endocarditis, 38 (21%)
underwent open heart surgery. Two patients were excluded due to missing
information leaving 36 patients for analysis. The number of operations steadily
increased, or from 8 to 21 during the first and last 5-years of the study period
(OR: 1.12, 95% CI: 1.05-1.21, p=0.002). The most common pathogen was S. aureus
and 81% (29/36) of the patients had positive blood cultures. Three patients had
history of previous cardiac surgery and five had history of intravenous drug
abuse. The aortic valve was most often infected (72%), followed by the mitral
valve (28%). The infected valve was replaced in 35 cases 14 with a mechanical
prosthesis and 20 with a bioprosthesis. In addition two mitral valves were
repaired. Postoperative complications included perioperative myocardial
infarction (35%), respiratory failure (44%) and reoperation for bleeding (25%).
Thirty-day mortality was 11% (4 patients) with 5- and 10-year survival of 59% and
49%, respectively. CONCLUSION: One out of five patients with endocarditis
underwent surgery, most commonly aortic or mitral valve replacement. Outcomes
were comparable to other studies. In comparison to elective valve replace-ment
surgery the rate of post-operative complications and 30-day mortality were higher
and long-term survival was less favorable. Key words: Endocarditis, surgical
treatment, valve replacement, complications, outcome. Correspondence: Arnar
Geirsson, arnargeirsson@yahoo.com.
PMID- 28489013
TI - [Incidence, cause and treatment of colonic perforations in Iceland 1998-2007: A
nationwide study].
AB - INTRODUCTION: Colon perforation is a serious illness with mortality reported from
0-39%. Surgery used to be the gold standard but treatment has changed as studies
have indicated comparable results with less invasive treatment. The aim of this
study was to evaluate the incidence of acute colon perforations in Iceland,
causes and treatment. MATERIAL AND METHODS: A retrospective, nationwide,
multicenter analysis was performed based on ICD-10 codes from databases of the
main hospitals in Iceland. Age, gender, year of perforation, cause, means of
diagnosis, treatment and outcome were registered. Patients under 18 years and
post mortem diagnosis were excluded. RESULTS: 225 patients met criteria, 131
women (58%) and 94 men (42%), median age 70 years (range 30-95). The most common
causes were diverticulitis (67%), colonoscopy (12%) and complications during
operations (5%). During the first five study years, 27% received conservative
treatment while 71% underwent surgery. By the end of the study era this ratio was
45% and 54% respectively. The rate of permanent stoma was 10%. CONCLUSIONS:
Diverticulitis was the most common cause of colon perforation in Iceland during
the study period. Many patients still undergo surgery but there has been a
dramatic change toward more conservative treatment. The rate of stoma closure is
comparable to studies elsewhere. 1University Hospital of Iceland, Dept. General
Surgery, 2University of Iceland, Faculty of Medicine, 3Akureyri Teaching
Hospital, 4Akranes Hospital and Health Care Center, Iceland. Key words: Colon
perforation, diverticulitis, Hartmann's reversal. Correspondence: Elsa B.
Valsdottir, elsava@landspitali.is.
PMID- 28489015
TI - Tracking the evolution of causal cognition in humans.
AB - We suggest a seven-grade model for the evolution of causal cognition as a
framework that can be used to gauge variation in the complexity of causal
reasoning from the panin-hominin split until the appearance of cognitively modern
hunter-gatherer communities. The intention is to put forward a cohesive model for
the evolution of causal cognition in humans, which can be assessed against
increasingly fine-grained empirical data from the palaeoanthropological and
archaeological records. We propose that the tracking behaviour (i.e., the ability
to interpret and follow external, inanimate, visual clues of hominins) provides a
rich case study for tracing the evolution of causal cognition in our lineage. The
grades of causal cognition are tentatively linked to aspects of the Stone
Age/Palaeolithic archaeological record. Our model can also be applied to current
work in evolutionary psychology and research on causal cognition, so that an
inter-disciplinary understanding and correlation of processes becomes
increasingly possible.
PMID- 28489016
TI - Carbon nanotube entangled Mn3O4 octahedron as anode materials for lithium-ion
batteries.
AB - A nanocomposite of Mn3O4 octahedrons entangled by carbon nanotubes (CNTs) was
synthesized by a hydrothermal method assisted with a non-ionic surfactant. The
integration of octahedral structure and CNTs could offer many critical features,
which are needed for high activity anodes, such as fast ion diffusion, good
electronic conductivity, and skeleton supporting function, thus enabling the
nanocomposite-based anodes with excellent electrochemical performance. In
addition, CNTs can not only serve as the conductive network and structure
skeleton to improve the anode performance, but also play an indispensable role in
the formation of more uniform Mn3O4 octahedrons. The lithium-ion batteries based
on the CNTs-entangled Mn3O4 octahedrons delivered a high capacity of over 800 mAh
g-1 at a current density of 0.2 C for 200 cycles, and even as high as 678.4 mAh g
1 when cycled at 0.5 C after 400 cycles, exhibiting a high capability and
ultralong cycle life.
PMID- 28489017
TI - Corrigendum:(2013 Nanotechnology {?bf 24} 395702)]{Corrigendum: Frequency tuning,
nonlinearities and mode coupling in circular mechanical graphene resonators (2013
Nanotechnology {?bf 24} 395702).
AB - N/A.
PMID- 28489018
TI - Estimating sleep parameters using nasal pressure signals applicable to continuous
positive airway pressure devices.
AB - OBJECTIVE: This paper proposes a method for classifying sleep-wakefulness and
estimating sleep parameters using nasal pressure signals applicable to a
continuous positive airway pressure (CPAP) device. APPROACH: In order to classify
the sleep-wakefulness states of patients with sleep-disordered breathing (SDB),
apnea-hypopnea and snoring events are first detected. Epochs detected as SDB are
classified as sleep, and time-domain- and frequency-domain-based features are
extracted from the epochs that are detected as normal breathing. Subsequently,
sleep-wakefulness is classified using a support vector machine (SVM) classifier
in the normal breathing epoch. Finally, four sleep parameters-sleep onset, wake
after sleep onset, total sleep time and sleep efficiency-are estimated based on
the classified sleep-wakefulness. In order to develop and test the algorithm, 110
patients diagnosed with SDB participated in this study. Ninety of the subjects
underwent full-night polysomnography (PSG) and twenty underwent split-night PSG.
The subjects were divided into 50 patients of a training set (full/split: 42/8),
30 of a validation set (full/split: 24/6) and 30 of a test set (full/split:
24/6). MAIN RESULTS: In the experiments conducted, sleep-wakefulness
classification accuracy was found to be 83.2% in the test set, compared with the
PSG scoring results of clinical experts. Furthermore, all four sleep parameters
showed higher correlations than the results obtained via PSG (r ? 0.84, p <
0.05). In order to determine whether the proposed method is applicable to CPAP,
sleep-wakefulness classification performances were evaluated for each CPAP in the
split-night PSG data. The results indicate that the accuracy and sensitivity of
sleep-wakefulness classification by CPAP variation shows no statistically
significant difference (p < 0.05). SIGNIFICANCE: The contributions made in this
study are applicable to the automatic classification of sleep-wakefulness states
in CPAP devices and evaluation of the quality of sleep.
PMID- 28489019
TI - Heart sound classification from unsegmented phonocardiograms.
AB - OBJECTIVE: Most algorithms for automated analysis of phonocardiograms (PCG)
require segmentation of the signal into the characteristic heart sounds. The aim
was to assess the feasibility for accurate classification of heart sounds on
short, unsegmented recordings. APPROACH: PCG segments of 5 s duration from the
PhysioNet/Computing in Cardiology Challenge database were analysed. Initially the
5 s segment at the start of each recording (seg 1) was analysed. Segments were
zero-mean but otherwise had no pre-processing or segmentation. Normalised
spectral amplitude was determined by fast Fourier transform and wavelet entropy
by wavelet analysis. For each of these a simple single feature threshold-based
classifier was implemented and the frequency/scale and thresholds for optimum
classification accuracy determined. The analysis was then repeated using
relatively noise free 5 s segments (seg 2) of each recording. Spectral amplitude
and wavelet entropy features were then combined in a classification tree. MAIN
RESULTS: There were significant differences between normal and abnormal
recordings for both wavelet entropy and spectral amplitude across scales and
frequency. In the wavelet domain the differences between groups were greatest at
highest frequencies (wavelet scale 1, pseudo frequency 1 kHz) whereas in the
frequency domain the differences were greatest at low frequencies (12 Hz).
Abnormal recordings had significantly reduced high frequency wavelet entropy:
(Median (interquartile range)) 6.63 (2.42) versus 8.36 (1.91), p < 0.0001,
suggesting the presence of discrete high frequency components in these
recordings. Abnormal recordings exhibited significantly greater low frequency (12
Hz) spectral amplitude: 0.24 (0.22) versus 0.09 (0.15), p < 0.0001.
Classification accuracy (mean of specificity and sensitivity) was greatest for
wavelet entropy: 76% (specificity 54%, sensitivity 98%) versus 70% (specificity
65%, sensitivity 75%) and was further improved by selecting the lowest noise
segment (seg 2): 80% (specificity 65%, sensitivity 94%) versus 71% (specificity
63%, sensitivity 79%). Classification tree with combined features gave accuracy
79% (specificity 80%, sensitivity 77%). SIGNIFICANCE: The feasibility of accurate
classification without segmentation of the characteristic heart sounds has been
demonstrated. Classification accuracy is comparable to other algorithms but
achieved without the complexity of segmentation.
PMID- 28489020
TI - Correspondence between visual and electrical input filters of ON and OFF mouse
retinal ganglion cells.
AB - OBJECTIVE: Over the past two decades retinal prostheses have made major strides
in restoring functional vision to patients blinded by diseases such as retinitis
pigmentosa. Presently, implants use single pulses to activate the retina. Though
this stimulation paradigm has proved beneficial to patients, an unresolved
problem is the inability to selectively stimulate the on and off visual pathways.
To this end our goal was to test, using white noise, voltage-controlled,
cathodic, monophasic pulse stimulation, whether different retinal ganglion cell
(RGC) types in the wild type retina have different electrical input filters. This
is an important precursor to addressing pathway-selective stimulation. APPROACH:
Using full-field visual flash and electrical and visual Gaussian noise
stimulation, combined with the technique of spike-triggered averaging (STA), we
calculate the electrical and visual input filters for different types of RGCs
(classified as on, off or on-off based on their response to the flash stimuli).
MAIN RESULTS: Examining the STAs, we found that the spiking activity of on cells
during electrical stimulation correlates with a decrease in the voltage magnitude
preceding a spike, while the spiking activity of off cells correlates with an
increase in the voltage preceding a spike. No electrical preference was found for
on-off cells. Comparing STAs of wild type and rd10 mice revealed narrower
electrical STA deflections with shorter latencies in rd10. SIGNIFICANCE: This
study is the first comparison of visual cell types and their corresponding
temporal electrical input filters in the retina. The altered input filters in
degenerated rd10 retinas are consistent with photoreceptor stimulation underlying
visual type-specific electrical STA shapes in wild type retina. It is therefore
conceivable that existing implants could target partially degenerated
photoreceptors that have only lost their outer segments, but not somas, to
selectively activate the on and off visual pathways.
PMID- 28489022
TI - Lactic Fermentation as an Efficient Tool to Enhance the Antioxidant Activity of
Tropical Fruit Juices and Teas.
AB - Tropical fruits like pineapple, papaya, mango, and beverages such as green or
black teas, represent an underestimated source of antioxidants that could exert
health-promoting properties. Most food processing technologies applied to fruit
beverages or teas result in an impairment of inherent nutritional properties.
Conversely, we hypothesise that lactic acid fermentation may constitute a
promising route to maintain and even improve the nutritional qualities of
processed fruits. Using specific growth media, lactic acid bacteria were selected
from the fruit phyllosphere diversity and fruit juice, with the latter undergoing
acidification kinetics analyses and characterised for exopolysaccharide
production. Strains able to ferment tropical fruit juices or teas into pleasant
beverages, within a short time, were of particular interest. Strains Weissella
cibaria 64 and Leuconostoc mesenteroides 12b, able to increase antioxidant
activity, were specifically studied as potential starters for lactic fermented
pineapple juice.
PMID- 28489021
TI - Calcium Dynamics Mediated by the Endoplasmic/Sarcoplasmic Reticulum and Related
Diseases.
AB - The flow of intracellular calcium (Ca2+) is critical for the activation and
regulation of important biological events that are required in living organisms.
As the major Ca2+ repositories inside the cell, the endoplasmic reticulum (ER)
and the sarcoplasmic reticulum (SR) of muscle cells are central in maintaining
and amplifying the intracellular Ca2+ signal. The morphology of these organelles,
along with the distribution of key calcium-binding proteins (CaBPs), regulatory
proteins, pumps, and receptors fundamentally impact the local and global
differences in Ca2+ release kinetics. In this review, we will discuss the
structural and morphological differences between the ER and SR and how they
influence localized Ca2+ release, related diseases, and the need for targeted
genetically encoded calcium indicators (GECIs) to study these events.
PMID- 28489023
TI - High Sensitivity Determination of TNF-alpha for Early Diagnosis of Neonatal
Infections with a Novel and Reusable Electrochemical Sensor.
AB - Early diagnosis is vital for the reduction of mortality caused by neonatal
infections. Since TNF-alpha can be used as a marker for the early diagnosis, the
detection of TNF-alpha with high sensitivity and specificity has great clinical
significance. Herein, a highly sensitive and reusable electrochemical sensor was
fabricated. Due to the high specificity of aptamers, TNF-alpha could be
accurately detected from five similar cytokines, even from serum samples. In
addition, Au nanoparticles (AuNPs) with a high surface area were able to combine
a large number of doxorubicin hydrochloride (DOXh), which made the sensor have a
high sensitivity. The sensor had a good linear relationship with TNF-alpha
concentration in the range from 1 to 1 * 104 pg/mL and the lowest detection limit
is 0.7 pg/mL. More important was that the sensor could be reused 6 times by a
crafty use of chain replacement reaction. Meanwhile, the detection time and cost
were greatly reduced. Thus, we believe that these advantages of higher
specificity and sensitivity, lower cost, and shorter detection time will provide
a stronger potential for early diagnosis of neonatal infections in clinical
applications.
PMID- 28489025
TI - Plasticizing Effects of Polyamines in Protein-Based Films.
AB - Zeta potential and nanoparticle size were determined on film forming solutions of
native and heat-denatured proteins of bitter vetch as a function of pH and of
different concentrations of the polyamines spermidine and spermine, both in the
absence and presence of the plasticizer glycerol. Our results showed that both
polyamines decreased the negative zeta potential of all samples under pH 8.0 as a
consequence of their ionic interaction with proteins. At the same time, they
enhanced the dimension of nanoparticles under pH 8.0 as a result of
macromolecular aggregations. By using native protein solutions, handleable films
were obtained only from samples containing either a minimum of 33 mM glycerol or
4 mM spermidine, or both compounds together at lower glycerol concentrations.
However, 2 mM spermidine was sufficient to obtain handleable film by using heat
treated samples without glycerol. Conversely, brittle materials were obtained by
spermine alone, thus indicating that only spermidine was able to act as an ionic
plasticizer. Lastly, both polyamines, mainly spermine, were found able to act as
"glycerol-like" plasticizers at concentrations higher than 5 mM under
experimental conditions at which their amino groups are undissociated. Our
findings open new perspectives in obtaining protein-based films by using
aliphatic polycations as components.
PMID- 28489024
TI - The Role of the N-Terminal Domains of Bacterial Initiator DnaA in the Assembly
and Regulation of the Bacterial Replication Initiation Complex.
AB - The primary role of the bacterial protein DnaA is to initiate chromosomal
replication. The DnaA protein binds to DNA at the origin of chromosomal
replication (oriC) and assembles into a filament that unwinds double-stranded
DNA. Through interaction with various other proteins, DnaA also controls the
frequency and/or timing of chromosomal replication at the initiation step.
Escherichia coli DnaA also recruits DnaB helicase, which is present in unwound
single-stranded DNA and in turn recruits other protein machinery for replication.
Additionally, DnaA regulates the expression of certain genes in E. coli and a few
other species. Acting as a multifunctional factor, DnaA is composed of four
domains that have distinct, mutually dependent roles. For example, C-terminal
domain IV interacts with double-stranded DnaA boxes. Domain III drives ATP
dependent oligomerization, allowing the protein to form a filament that unwinds
DNA and subsequently binds to and stabilizes single-stranded DNA in the initial
replication bubble; this domain also interacts with multiple proteins that
control oligomerization. Domain II constitutes a flexible linker between C
terminal domains III-IV and N-terminal domain I, which mediates intermolecular
interactions between DnaA and binds to other proteins that affect DnaA activity
and/or formation of the initiation complex. Of these four domains, the role of
the N-terminus (domains I-II) in the assembly of the initiation complex is the
least understood and appears to be the most species-dependent region of the
protein. Thus, in this review, we focus on the function of the N-terminus of DnaA
in orisome formation and the regulation of its activity in the initiation complex
in different bacteria.
PMID- 28489026
TI - Redox Regulation of the Tumor Suppressor PTEN by Hydrogen Peroxide and Tert-Butyl
Hydroperoxide.
AB - Organic peroxides and hydroperoxides are skin tumor promoters. Free radical
derivatives from these compounds are presumed to be the prominent mediators of
tumor promotion. However, the molecular targets of these species are unknown.
Phosphatase and tensin homologs deleted on chromosome 10 (PTEN) are tumor
suppressors that play important roles in cell growth, proliferation, and cell
survival by negative regulation of phosphoinositol-3-kinase/protein kinase B
signaling. PTEN is reversibly oxidized in various cells by exogenous and
endogenous hydrogen peroxide. Oxidized PTEN is converted back to the reduced form
by cellular reducing agents, predominantly by the thioredoxin (Trx) system. Here,
the role of tert-butyl hydroperoxide (t-BHP) in redox regulation of PTEN was
analyzed by using cell-based and in vitro assays. Exposure to t-BHP led to
oxidation of recombinant PTEN. In contrast to H2O2, PTEN oxidation by t-BHP was
irreversible in HeLa cells. However, oxidized PTEN was reduced by exogenous Trx
system. Taken together, these results indicate that t-BHP induces PTEN oxidation
and inhibits Trx system, which results in irreversible PTEN oxidation in HeLa
cells. Collectively, these results suggest a novel mechanism of t-BHP in the
promotion of tumorigenesis.
PMID- 28489027
TI - Direct Analyses of Secondary Metabolites by Mass Spectrometry Imaging (MSI) from
Sunflower (Helianthus annuus L.) Trichomes.
AB - Helianthus annuus (sunflower) displays non-glandular trichomes (NGT), capitate
glandular trichomes (CGT), and linear glandular trichomes (LGT), which reveal
different chemical compositions and locations in different plant tissues. With
matrix-assisted laser desorption/ionization (MALDI) and laser
desorption/ionization (LDI) mass spectrometry imaging (MSI) techniques, efficient
methods were developed to analyze the tissue distribution of secondary
metabolites (flavonoids and sesquiterpenes) and proteins inside of trichomes.
Herein, we analyzed sesquiterpene lactones, present in CGT, from leaf transversal
sections using the matrix 2,5-dihydroxybenzoic acid (DHB) and alpha-cyano-4
hydroxycinnamic acid (CHCA) (mixture 1:1) with sodium ions added to increase the
ionization in positive ion mode. The results observed for sesquiterpenes and
polymethoxylated flavones from LGT were similar. However, upon desiccation, LGT
changed their shape in the ionization source, complicating analyses by MSI mainly
after matrix application. An alternative method could be applied to LGT regions
by employing LDI (without matrix) in negative ion mode. The polymethoxylated
flavones were easily ionized by LDI, producing images with higher resolution, but
the sesquiterpenes were not observed in spectra. Thus, the application and
viability of MALDI imaging for the analyses of protein and secondary metabolites
inside trichomes were confirmed, highlighting the importance of optimization
parameters.
PMID- 28489028
TI - Synthesis and Characterization of Nano-Conducting Copolymer Composites: Efficient
Sorbents for Organic Pollutants.
AB - Nano-conducting copolymers of aniline (ANI) and pyrrole (Py) with silica of
different starting monomer ratios are prepared by oxidative chemical
polymerization. X-ray diffraction (XRD) data showed that polyaniline (PANI) is
the predominant phase in copolymer composites with a higher starting ANI monomer
ratio while polypyrrole (PPy) is the major phase for other prepared samples.
Transmission and scanning electron microscope images ascertained XRD results
where hexagonal-shaped particles are assigned to PANI/SiO2 and poly(9ANI-co
1Py)/SiO2 samples; the cauliflower morphology can be observed for PPy/SiO2,
poly(1ANI-co-9Py)/SiO2, poly(1ANI-co-2Py)/SiO2, and poly(1ANI-co-1Py)/SiO2
samples. One-dimensional nano-fibers can be obtained by using a starting monomer
ratio of 2ANI:1Py during synthesis. Thermal analysis showed that copolymerization
increases the thermal stability as compared with PANI/SiO2 and PPy/SiO2
composites. All prepared samples were applied as sorbents for Congo red dye from
aqueous solutions. It was found that the sorption capacity value was affected by
the starting monomer ratio; poly(2ANI-co-1Py)/SiO2 has the highest sorption
capacity; the qm value is 142.9 mg g-1 due to its highly-stabilized nano
structure.
PMID- 28489029
TI - Comparative Analysis of the Major Chemical Constituents in Salvia miltiorrhiza
Roots, Stems, Leaves and Flowers during Different Growth Periods by UPLC-TQ-MS/MS
and HPLC-ELSD Methods.
AB - Salvia miltiorrhiza is a traditional Chinese herbal medicine containing multiple
components that contribute to its notable bioactivities. This article
investigated the distribution and dynamic changes of chemical constituents in
various parts of S. miltiorrhiza from different growth periods. An ultra-high
performance liquid chromatography-triple quadrupole mass spectrometer (UPLC-TQ
MS/MS) and high-performance liquid chromatography coupled with evaporative light
scattering detector (HPLC-ELSD) methods were developed for accurate determination
of 24 compounds (including phenolic acids, flavonoids, triterpenes, and
saccharides) in S. miltiorrhiza. The established methods were validated with good
linearity, precision, repeatability, stability, and recovery. Results indicated
that there were category and quantity discrepancies in different parts of the
plant, for the roots mainly contained salvianolic acids and tanshinones, and most
of the saccharides are stachyose. In the aerial parts, salvianolic acids,
flavonoids, and triterpenes, except the tanshinones, were detected, and the
saccharides were mainly monosaccharides. Dynamic accumulation analysis suggested
the proper harvest time for S. miltiorrhiza Bunge was the seedling stage in
spring, and for the aerial parts was July to August. This study provided valuable
information for the development and utilization value of the aerial parts of S.
miltiorrhiza and was useful for determining the optimal harvest time of the
plant.
PMID- 28489031
TI - Effect of Cold Storage and Reheating of Parboiled Rice on Postprandial Glycaemic
Response, Satiety, Palatability and Chewed Particle Size Distribution.
AB - Background: Globally, hot cooked refined rice is consumed in large quantities and
is a major contributor to dietary glycaemic load. This study aimed to compare the
glycaemic potency of hot- and cold-stored parboiled rice to widely available
medium-grain white rice. Method: Twenty-eight healthy volunteers participated in
a three-treatment experiment where postprandial blood glucose was measured over
120 min after consumption of 140 g of rice. The three rice samples were freshly
cooked medium-grain white rice, freshly cooked parboiled rice, and parboiled rice
stored overnight at 4 degrees C. All rice was served warm at 65 degrees C.
Chewing time was recorded. Results: incremental area under the curve (iAUC) of
the control rice, freshly cooked medium-grain white rice, was the highest: 1.7
fold higher (1.2, 2.6) than reheated parboiled rice (p < 0.001) and 1.5-fold
higher (1.0, 2.2) than freshly cooked parboiled rice (p = 0.001). No significant
difference in postprandial glycaemic response was observed between freshly cooked
and reheated parboiled rice samples (p = 0.445). Chewing time for 10 g cold
stored parboiled rice was 6 s (25%) longer and was considered more palatable,
visually appealing and better tasting than freshly cooked medium-grain (all p <
0.05). Conclusions: For regular consumers of rice, reheating cooked rice after
cold storage would lower the dietary glycaemic load and, in the long term, may
reduce the risk for type 2 and gestational diabetes. More trials are needed to
identify the significance.
PMID- 28489030
TI - A Review of Recruitment, Adherence and Drop-Out Rates in Omega-3 Polyunsaturated
Fatty Acid Supplementation Trials in Children and Adolescents.
AB - INTRODUCTION: The influence of n-3 long-chain polyunsaturated fatty acids (n-3
LCPUFA) supplementation on health outcomes has been studied extensively with
randomized controlled trials (RCT). In many research fields, difficulties with
recruitment, adherence and high drop-out rates have been reported. However, what
is unknown is how common these problems are in n-3 LCPUFA supplementation studies
in children and adolescents. Therefore, this paper will review n-3 LCPUFA
supplementation studies in children and adolescents with regard to recruitment,
adherence and drop-out rates. METHODS: The Web of Science, PubMed and Ovid
databases were searched for papers reporting on RCT supplementing children and
adolescents (2-18 years) with a form of n-3 LCPUFA (or placebo) for at least four
weeks. As a proxy for abiding to CONSORT guidelines, we noted whether manuscripts
provided a flow-chart and provided dates defining the period of recruitment and
follow-up. RESULTS: Ninety manuscripts (reporting on 75 studies) met the
inclusion criteria. The majority of the studies did not abide by the CONSORT
guidelines: 55% did not provide a flow-chart, while 70% did not provide dates.
The majority of studies provided minimal details about the recruitment process.
Only 25 of the 75 studies reported an adherence rate which was on average 85%.
Sixty-five of the 75 studies included drop-out rates which were on average 17%.
CONCLUSION: Less than half of the included studies abided by the CONSORT
guidelines (45% included a flow chart, while 30% reported dates). Problems with
recruitment and drop-out seem to be common in n-3 LCPUFA supplementation trials
in children and adolescents. However, reporting about recruitment, adherence and
dropout rates was very heterogeneous and minimal in the included studies. Some
techniques to improve recruitment, adherence and dropout rates were identified
from the literature, however these techniques may need to be tailored to n-3
LCPUFA supplementation studies in children and adolescents.
PMID- 28489032
TI - Clinical Significance and Prognostic Effect of Serum 25-hydroxyvitamin D
Concentrations in Critical and Severe Hand, Foot and Mouth Disease.
AB - OBJECTIVE: To examine the association of serum 25-hydroxyvitamin D [25(OH)D]
concentrations with critical and severe hand, foot and mouth disease (HFMD) and
assess the clinical significance and prognostic effect of 25(OH)D concentrations
in children with HFMD. METHODS: This is a prospective observational study. The
138 children with HFMD were divided into common (49 cases), severe (52 cases),
and critical (37 cases) HFMD groups. Another 59 healthy children undergoing
outpatient medical examinations during the same period were chosen as the control
group. Serum 25(OH)D concentrations were measured in all the subjects, and each
group was subdivided by serum 25(OH)D concentration into 25(OH)D normal (>=30
ng/mL); insufficiency (20-29.9 ng/mL), and deficiency (<20 ng/mL) groups. The
pediatric critical illness score (PCIS) was recorded for the critical and severe
HFMD group upon admission to the pediatric intensive care unit (PICU). Children
with critical and severe HFMD were also monitored for blood lactate (LAC), serum
calcium ions (Ca++), D-dimer (DD), lactate dehydrogenase (LDH), and creatine
kinase-MB (CK-MB) levels; the incidences of brainstem encephalitis, neurogenic
pulmonary edema, and circulatory failure; and the 14-day mortality rate. RESULTS:
Serum 25(OH)D concentrations were generally low in all groups. The critical HFMD
group showed a significantly lower serum 25(OH)D mean concentration (20.0 +/- 8.4
ng/mL) and a higher proportion of deficiency (18%) compared with the control
group (28.1 +/- 6.6 ng/mL, 8%), common (29.5 +/- 8.1 ng/mL, 10%) and severe (31.9
+/- 9.7 ng/mL, 8%) HFMD groups (p < 0.05). In the critical and severe HFMD
groups, the 25(OH)D deficiency group had lower PCISs than the 25(OH)D normal and
insufficiency groups (p < 0.05); and had higher values than the latter two groups
for LAC, LDH, CK-MB and DD; and the incidences of brainstem encephalitis,
neurogenic pulmonary edema, circulatory failure, and mortality (p < 0.05). The
death group showed significantly lower serum 25(OH)D concentrations and PCISs
than the survival group (p < 0.05) and had higher LAC, LDH, CK-MB and DD levels
and higher incidences of brainstem encephalitis, neurogenic pulmonary edema, and
circulatory failure (p < 0.05). Logistic regression analysis revealed that the
serum 25(OH)D concentration was an independent factor that influenced mortality
in children with critical and severe HFMD. CONCLUSIONS: In this study, we find
the serum 25(OH)D concentrations are substantially reduced in children with
critical and severe HFMD and are associated with the severity of HFMD. The serum
25(OH)D concentrations may have clinical value for determining the progression of
critical HFMD and predicting the risk of death. Further evidence is needed before
it can be stated that 25(OH)D concentrations have clinical value in HMFD
diagnosis.
PMID- 28489033
TI - Efficient Fluorescence Resonance Energy Transfer between Quantum Dots and Gold
Nanoparticles Based on Porous Silicon Photonic Crystal for DNA Detection.
AB - A novel assembled biosensor was prepared for detecting 16S rRNA, a small-size
persistent specific for Actinobacteria. The mechanism of the porous silicon (PS)
photonic crystal biosensor is based on the fluorescence resonance energy transfer
(FRET) between quantum dots (QDs) and gold nanoparticles (AuNPs) through DNA
hybridization, where QDs act as an emission donor and AuNPs serve as a
fluorescence quencher. Results showed that the photoluminescence (PL) intensity
of PS photonic crystal was drastically increased when the QDs-conjugated probe
DNA was adhered to the PS layer by surface modification using a standard cross
link chemistry method. The PL intensity of QDs was decreased when the addition of
AuNPs-conjugated complementary 16S rRNA was dropped onto QDs-conjugated PS. Based
on the analysis of different target DNA concentration, it was found that the
decrease of the PL intensity showed a good linear relationship with complementary
DNA concentration in a range from 0.25 to 10 MUM, and the detection limit was
328.7 nM. Such an optical FRET biosensor functions on PS-based photonic crystal
for DNA detection that differs from the traditional FRET, which is used only in
liquid. This method will benefit the development of a new optical FRET label-free
biosensor on Si substrate and has great potential in biochips based on integrated
optical devices.
PMID- 28489034
TI - The Prevalence of Vitamin D Insufficiency and Deficiency and Their Relationship
with Bone Mineral Density and Fracture Risk in Adults Receiving Long-Term Home
Parenteral Nutrition.
AB - It has been demonstrated that low bone mass and vitamin D deficiency occur in
adult patients receiving home parenteral nutrition (HPN). The aim of this study
is to determine the prevalence of vitamin D insufficiency and deficiency and its
relationship with bone mineral density (BMD) and fracture risk in long-term HPN
patients. Methods: A retrospective chart review of all 186 patients in the HPN
registry followed by the Northern Alberta Home Parenteral Nutrition Program
receiving HPN therapy >6 months with a 25 (OH) D level and BMD reported were
studied. Results: The mean age at the initiation of HPN was 53.8 (20-79) years
and 23 (37%) were male. The mean HPN duration was 56 (6-323) months and the most
common diagnosis was short bowel syndrome. Based on a total of 186 patients, 62
patients were categorized based on serum vitamin D status as follows: 1 (24.2%)
sufficient, 31 (50%) insufficient and 16 (25.8%) deficient. Despite an average of
1891 IU/day orally and 181 IU/day intravenously vitamin D, the mean vitamin D
level was 25.6 ng/mL (insufficiency) and 26.2 +/- 11.9 ng/mL in patients with the
highest 10-year fracture risk. Conclusion: Suboptimal vitamin D levels are common
among patients on long-term HPN despite nutrient intake that should meet
requirements.
PMID- 28489035
TI - Development of Conductivity Sensors for Multi-Phase Flow Local Measurements at
the Polytechnic University of Valencia (UPV) and University Jaume I of Castellon
(UJI).
AB - This paper describes all the procedures and methods currently used at UPV
(Universitat Politecnica de Valencia) and UJI (University Jaume I) for the
development and use of sensors for multi-phase flow analysis in vertical pipes.
This paper also describes the methods that we use to obtain the values of the two
phase flow magnitudes from the sensor signals and the validation and cross
verification methods developed to check the consistency of the results obtained
for these magnitudes with the sensors. First, we provide information about the
procedures used to build the multi-sensor conductivity probes and some of the
tests performed with different materials to avoid sensor degradation issues. In
addition, we provide information about the characteristics of the electric
circuits that feed the sensors. Then the data acquisition of the conductivity
probe, the signal conditioning and the data processing including the device that
have been designed to automatize all the measurement process of moving the
sensors inside the channels by means of stepper electric motors controlled by
computer are shown in operation. Then, we explain the methods used for bubble
identification and categorization. Finally, we describe the methodology used to
obtain the two-phase flow information from the sensor signals. This includes the
following items: void fraction, gas velocity, Sauter mean diameter and
interfacial area concentration. The last part of this paper is devoted to the
conductance probes developed for the annular flow analysis, which includes the
analysis of the interfacial waves produced in annular flow and that requires a
different type of sensor.
PMID- 28489036
TI - GryphSens: A Smartphone-Based Portable Diagnostic Reader for the Rapid Detection
of Progesterone in Milk.
AB - Enzyme-linked immunosorbent assay (ELISA) is a popular assay technique for the
detection and quantification of various biological substances due its high
sensitivity and specificity. More often, it requires large and expensive
laboratory instruments, which makes it difficult to conduct when the tests must
be performed quickly at the point-of-care (POC). To increase portability and ease
of use, we propose a portable diagnostic system based on a Raspberry Pi imaging
sensor for the rapid detection of progesterone in milk samples. We designed,
assembled, and tested a standalone portable diagnostic reader and validated it
for progesterone detection against a standard ELISA assay using a commercial
plate reader. The portable POC device yielded consistent results, regardless of
differences in the cameras and flashlights between various smartphone devices. An
Android application was built to provide front-end access to users, control the
diagnostic reader, and display and store the progesterone measurement on the
smartphone. The diagnostic reader takes images of the samples, reads the pixel
values, processes the results, and presents the results on the handheld device.
The proposed POC reader can perform to superior levels of performance as a plate
reader, while adding the desirable qualities of portability and ease of use.
PMID- 28489037
TI - Color-Coded Front-of-Pack Nutrition Labels-An Option for US Packaged Foods?
AB - The implementation of a standardized front-of-pack-labelling (FoPL) scheme would
likely be a useful tool for many consumers trying to improve the healthfulness of
their diets. Our objective was to examine what the traffic light labelling scheme
would look like if implemented in the US. Data were extracted from Label
Insight's Open Access branded food database in 2017. Nutrient levels and the
proportion of products classified as "Red" (High), "Amber" (Medium) or "Green"
(Low) in total fat, saturated fat, total sugar and sodium for food and beverage
items were examined. The proportion of products in each category that had each
possible combination of traffic light colors, and met the aggregate score for
"healthy" was examined. Out of 175,198 products, >50% of all US packaged foods
received a "Red" rating for total sugar and sodium. "Confectionery" had the
highest mean total sugar (51.9 g/100 g) and "Meat and meat alternatives" the
highest mean sodium (781 mg/100 g). The most common traffic light label
combination was "Red" for total fat, saturated fat and sodium and "Green" for
sugar. Only 30.1% of products were considered "healthy". A wide variety (n = 80)
of traffic light color combinations were observed. A color coded traffic light
scheme appears to be an option for implementation across the US packaged food
supply to support consumers in making healthier food choices.
PMID- 28489038
TI - Transparent Nanotubular TiO2 Photoanodes Grown Directly on FTO Substrates.
AB - This work describes the preparation of transparent TiO2 nanotube (TNT) arrays on
fluorine-doped tin oxide (FTO) substrates. An optimized electrolyte composition
(0.2 mol dm-3 NH4F and 4 mol dm-3 H2O in ethylene glycol) was used for the
anodization of Ti films with different thicknesses (from 100 to 1300 nm)
sputtered on the FTO glass substrates. For Ti thicknesses 600 nm and higher,
anodization resulted in the formation of TNT arrays with an outer nanotube
diameter around 180 nm and a wall thickness around 45 nm, while for anodized Ti
thicknesses of 100 nm, the produced nanotubes were not well defined. The
transmittance in the visible region (lambda = 500 nm) varied from 90% for the
thinnest TNT array to 65% for the thickest TNT array. For the fabrication of
transparent TNT arrays by anodization, the optimal Ti thickness on FTO was around
1000 nm. Such fabricated TNT arrays with a length of 2500 nm exhibit stable
photocurrent densities in aqueous electrolytes (~300 uA cm-2 at potential 0.5 V
vs. Ag/AgCl). The stability of the photocurrent response and a sufficient
transparency (>=65%) enables the use of transparent TNT arrays in
photoelectrochemical applications when the illumination from the
support/semiconductor interface is a necessary condition and the transmitted
light can be used for another purpose (photocathode or photochemical reaction in
the electrolyte).
PMID- 28489039
TI - Third Generation Antivenomics: Pushing the Limits of the In Vitro Preclinical
Assessment of Antivenoms.
AB - Second generation antivenomics is a translational venomics approach designed to
complement in vivo preclinical neutralization assays. It provides qualitative and
quantitative information on the set of homologous and heterologous venom proteins
presenting antivenom-recognized epitopes and those exhibiting impaired
immunoreactivity. In a situation of worrying antivenom shortage in many tropical
and sub-tropical regions with high snakebite mortality and morbidity rates, such
knowledge has the potential to facilitate the optimal deployment of currently
existing antivenoms and to aid in the rational design of novel broad specificity
antidotes. The aim of the present work was to expand the analytical capability of
the immunoaffinity second-generation antivenomics platform, endowing it with the
ability to determine the maximal binding capacity of an antivenom toward the
different toxins present in a venom, and to quantify the fraction of venom
specific antibodies present in a given antivenom. The application of this new
platform, termed third generation (3G) antivenomics, in the preclinical
evaluation of antivenoms is illustrated in this paper for the case of antivenom
EchiTAb-Plus-ICP(r) reactivity towards the toxins of homologous (B. arietans) and
heterologous (N. melanoleuca) venoms.
PMID- 28489040
TI - Nitride-Based Materials for Flexible MEMS Tactile and Flow Sensors in Robotics.
AB - The response to different force load ranges and actuation at low energies is of
considerable interest for applications of compliant and flexible devices
undergoing large deformations. We present a review of technological platforms
based on nitride materials (aluminum nitride and silicon nitride) for the
microfabrication of a class of flexible micro-electro-mechanical systems. The
approach exploits the material stress differences among the constituent layers of
nitride-based (AlN/Mo, Si x N y /Si and AlN/polyimide) mechanical elements in
order to create microstructures, such as upwardly-bent cantilever beams and bowed
circular membranes. Piezoresistive properties of nichrome strain gauges and
direct piezoelectric properties of aluminum nitride can be exploited for
mechanical strain/stress detection. Applications in flow and tactile sensing for
robotics are described.
PMID- 28489041
TI - Effect of Gamma Irradiation on 2-Acetyl-1-pyrroline Content, GABA Content and
Volatile Compounds of Germinated Rice (Thai Upland Rice).
AB - Aroma intensity in rice is related to the level of 2-acetyl-1-pyrroline (2AP).
The accumulation of 2AP in rice has been synthesized via l-proline metabolism by
inactive betaine aldehyde dehydrogenase enzyme (BADH2), which activates 2AP
accumulation. Meanwhile, active BADH2 inhibits 2AP accumulation but activates
gamma-aminobutyric acid (GABA) accumulation. The improvement of 2AP content in
rice has been reported under certain conditions, such as high salinity, water
treatment, and reduction of high intensity solar exposure. In this study, we
conducted the effects of gamma irradiation on 2AP content, GABA content and
volatile compounds of germinated rice (Thai upland rice). Our results showed that
the GABA content was highest when rice seeds germinated within a 24-h. The 2AP
content of irradiated rice (germinated within a 24-h duration) was higher than
non-irradiated rice for all gamma doses, particularly at 20 Gy, which showed a 23
fold higher level of 2AP than non-irradiated rice. On the other hand, the
reduction of the GABA content of irradiated rice was caused by an increase in the
gamma dose. At 300 Gy, irradiated rice had a GABA content approximately 2.6-fold
lower than non-irradiated rice. Moreover, we observed that a reduction of
volatile compounds occurred when increasing gamma dose. However, some volatile
compounds appeared in the irradiated rice at gamma doses of 60 Gy, 80 Gy, 100 Gy
and 300 Gy. Furthermore, we observed that the level of Octanal, which is the
compound most related to aroma intensity, of irradiated rice was stronger than
that of non-irradiated rice. Our results demonstrate for the first time that 2AP
and GABA contents are sensitive to gamma irradiation conditions. Moreover, the
results indicate that the gamma irradiation technique can be used to improve the
aroma intensity of rice.
PMID- 28489042
TI - Spatial Analysis of Ambient PM2.5 Exposure and Bladder Cancer Mortality in
Taiwan.
AB - Fine particulate matter (PM2.5) is an air pollutant that is receiving intense
regulatory attention in Taiwan. In previous studies, the effect of air pollution
on bladder cancer has been explored. This study was conducted to elucidate the
effect of atmospheric PM2.5 and other local risk factors on bladder cancer
mortality based on available 13-year mortality data. Geographically weighted
regression (GWR) was applied to estimate and interpret the spatial variability of
the relationships between bladder cancer mortality and ambient PM2.5
concentrations, and other variables were covariates used to adjust for the effect
of PM2.5. After applying a GWR model, the concentration of ambient PM2.5 showed a
positive correlation with bladder cancer mortality in males in northern Taiwan
and females in most of the townships in Taiwan. This is the first time PM2.5 has
been identified as a risk factor for bladder cancer based on the statistical
evidence provided by GWR analysis.
PMID- 28489043
TI - Underweight, Stunting and Wasting among Children in Kilimanjaro Region, Tanzania;
a Population-Based Cross-Sectional Study.
AB - This study assessed the prevalence and risk factors associated with underweight,
stunting and wasting among children aged 0-24 months in six districts of
Kilimanjaro region, northern Tanzania. A cross-sectional population-based study
using a multistage, proportionate to size sampling was conducted from June 2010
to March 2011. A structured questionnaire was used to collect sociodemographic,
economic, feeding and child information. Anthropometric data were collected by
trained field workers, and the data were used to assess child nutritional status.
A total of 1870 children were enrolled in this study. The prevalence of children
classified as underweight was 46.0%, stunting was 41.9%, and wasting was 24.7%.
About 33% were both underweight and stunted, and 12% had all three conditions. In
a multivariate logistic regression, child age, child being ill and birth weight
were associated with all anthropometric indices. Child being breastfed was
associated with being underweight and wasting. Mother's education was associated
with being underweight and stunting. Fathers aged 35+ years, and living in the
Hai district was associated with stunting, and being female was associated with
wasting. The prevalence of child undernutrition is high in this region.
Strategies that target each risk factor for child undernutrition may help to
reduce the problem in the region.
PMID- 28489045
TI - Discontinuity Detection in the Shield Metal Arc Welding Process.
AB - This work proposes a new methodology for the detection of discontinuities in the
weld bead applied in Shielded Metal Arc Welding (SMAW) processes. The detection
system is based on two sensors-a microphone and piezoelectric-that acquire
acoustic emissions generated during the welding. The feature vectors extracted
from the sensor dataset are used to construct classifier models. The approaches
based on Artificial Neural Network (ANN) and Support Vector Machine (SVM)
classifiers are able to identify with a high accuracy the three proposed weld
bead classes: desirable weld bead, shrinkage cavity and burn through
discontinuities. Experimental results illustrate the system's high accuracy,
greater than 90% for each class. A novel Hierarchical Support Vector Machine
(HSVM) structure is proposed to make feasible the use of this system in
industrial environments. This approach presented 96.6% overall accuracy. Given
the simplicity of the equipment involved, this system can be applied in the metal
transformation industries.
PMID- 28489044
TI - What Type of Transitional Care Effectively Reduced Mortality and Improved ADL of
Stroke Patients? A Meta-Analysis.
AB - Stroke is a major cause of disability and mortality worldwide; yet; prior to this
study; there had been no sufficient evidence to support the effectiveness of
various transitional care interventions (TCI) on the disability and mortality of
stroke survivors. This meta-analysis aimed to assess the effectiveness of TCI in
reducing mortality and improving the activities of daily life (ADL) of stroke
patients. PubMed; Web of Science; OVID; EMBASE; CINAHL; and Sino-Med were
searched for articles published before November 2016. Thirty-one randomized
controlled trials (RCTs) were identified in the study. This analysis showed that
the total effect of TCI on reducing mortality was limited (Risk Ratio (RR) =
0.86; 95% Confidence Interval (CI): 0.75-0.98); that only home-visiting programs
could reduce mortality rates (RR = 0.34; 95% CI: 0.17-0.67) compared with usual
care; and that the best intervention was led by a multidisciplinary team (MT) <=3
months (RR = 0.19; 95% CI: 0.05-0.71). In addition; home-visiting programs also
produced ADL benefit (RR = 0.56; 95% CI: 0.31-0.81). Overall; there was a
statistically significant difference in improving patients' independence between
TCI and usual care (RR = 1.12; 95% CI: 1.02-1.23). However; none of the
interventions was effective when they were differentiated in the analysis. It is
the conclusion of this study that home-visiting programs; especially those led by
MTs; should receive the greatest consideration by healthcare systems or providers
for implementing TCI to stroke survivors.
PMID- 28489046
TI - Validity of Research-Grade Actigraphy Unit for Measuring Exercise Intensity.
AB - This study was conducted in a free-living setting to investigate the measurement
validity of a research-based actigraph for strolling and jogging, and to provide
a reference for actual practice and research. Because inadequate physical
activity (PA) or sedentary lifestyle has become the fourth leading risk factor
for mortality worldwide, many countries have been vigorously promoting the
concept of "active living", and the public has been investing greater effort into
intensifying their PA. Although research-grade actigraphs have been widely
applied to evaluate PA in routine environments, the measurement results may not
accurately reflect the wearers' PA. Unlike most relevant research, which is
conducted in well-controlled laboratory environments, the present study was
implemented in the field to examine the sensitivity and convergent validity of
the MicroMini Motionlogger(r) Actigraph during strolling and jogging. The
following results were revealed: (1) Although the exercise movement speed while
jogging was significantly faster than that while strolling, the actigraph
readings showed no significant difference between strolling and jogging; (2) The
actigraph readings were (significantly or nonsignificantly) negatively correlated
with metabolic heat and nonsignificantly correlated with movement speeds. Hence,
the actigraph validity for measuring PA intensity while strolling and jogging
remains debatable.
PMID- 28489047
TI - The Broad Host Range and Genetic Diversity of Mammalian and Avian Astroviruses.
AB - Astroviruses are a diverse family of viruses that infect a wide range of
mammalian and avian hosts. Here we describe the phylogenetic diversity and
current classification methodology of astroviruses based on the ORF1b and ORF2
genes, highlighting the propensity of astroviruses to undergo interspecies
transmission and genetic recombination which greatly increase diversity and
complicate attempts at a unified and comprehensive classification strategy.
PMID- 28489048
TI - Multibehavioural Interventions with a Focus on Specific Energy Balance-Related
Behaviours Can Affect Diet Quality in Preschoolers from Six European Countries:
The ToyBox-Study.
AB - The present study aimed to examine whether a multibehavioural intervention with a
focus on specific energy balance-related behaviours can affect total diet quality
and its four subcomponents in European preschoolers and to investigate if these
intervention effects differed by socioeconomic status (SES). Parents/caregivers
of 3.5 to 5.5 year-olds (n = 4968) recruited through kindergartens in six
European countries within the ToyBox-study completed questionnaires on socio
demographics and a food frequency questionnaire on their preschoolers' diet. To
assess intervention effects and differences by SES, multilevel repeated measures
analyses were conducted. In contrast to no significant difference in total diet
quality, in both the intervention and control group, the dietary quality and
dietary equilibrium increased, with a larger increase in the intervention group
(mean difference quality: +3.4%; mean difference equilibrium: +0.9%) compared to
the control group (quality: +1.5%; equilibrium: +0.2%). SES was not a significant
moderator for intervention effects on total diet quality, nor for the four
subcomponents. This study indicates that multibehavioural interventions with a
focus on specific energy balance-related behaviours in preschoolers not only
affect those targeted behaviours, but can also have more generalized effects. The
ToyBox-intervention effects were similar for both lower and high SES
preschoolers.
PMID- 28489049
TI - Superparamagnetic Iron Oxide Nanoparticles-Complexed Cationic Amylose for In Vivo
Magnetic Resonance Imaging Tracking of Transplanted Stem Cells in Stroke.
AB - Cell-based therapy with mesenchymal stem cells (MSCs) is a promising strategy for
acute ischemic stroke. In vivo tracking of therapeutic stem cells with magnetic
resonance imaging (MRI) is imperative for better understanding cellular survival
and migrational dynamics over time. In this study, we develop a novel
biocompatible nanocomplex (ASP-SPIONs) based on cationic amylose, by introducing
spermine and the image label, ultrasmall superparamagnetic iron oxide
nanoparticles (SPIONs), to label MSCs. The capacity, efficiency, and cytotoxicity
of the nanocomplex in transferring SPIONs into green fluorescence protein
modified MSCs were tested; and the performance of in vivo MRI tracking of the
transplanted cells in acute ischemic stroke was determined. The results
demonstrated that the new class of SPIONs-complexed nanoparticles based on
biodegradable amylose can serve as a highly effective and safe carrier to
transfer magnetic label into stem cells. A reliable tracking of transplanted stem
cells in stroke was achieved by MRI up to 6 weeks, with the desirable therapeutic
benefit of stem cells on stroke retained. With the advantages of a relatively low
SPIONs concentration and a short labeling period, the biocompatible complex of
cationic amylose with SPIONs is highly translatable for clinical application. It
holds great promise in efficient, rapid, and safe labeling of stem cells for
subsequent cellular MRI tracking in regenerative medicine.
PMID- 28489051
TI - Vehicle Counting and Moving Direction Identification Based on Small-Aperture
Microphone Array.
AB - The varying trend of a moving vehicle's angles provides much important
intelligence for an unattended ground sensor (UGS) monitoring system. The present
study investigates the capabilities of a small-aperture microphone array (SAMA)
based system to identify the number and moving direction of vehicles travelling
on a previously established route. In this paper, a SAMA-based acoustic
monitoring system, including the system hardware architecture and algorithm
mechanism, is designed as a single node sensor for the application of UGS. The
algorithm is built on the varying trend of a vehicle's bearing angles around the
closest point of approach (CPA). We demonstrate the effectiveness of our proposed
method with our designed SAMA-based monitoring system in various experimental
sites. The experimental results in harsh conditions validate the usefulness of
our proposed UGS monitoring system.
PMID- 28489050
TI - An In Vivo Magnetic Resonance Spectroscopy Study of the Effects of Caloric and
Non-Caloric Sweeteners on Liver Lipid Metabolism in Rats.
AB - We aimed to elucidate the effects of caloric and non-caloric sweeteners on liver
lipid metabolism in rats using in vivo magnetic resonance spectroscopy (MRS) and
to determine their roles in the development of liver steatosis. Wistar rats
received normal chow and either normal drinking water, or solutions containing
13% (w/v) glucose, 13% fructose, or 0.4% aspartame. After 7 weeks, in vivo
hepatic dietary lipid uptake and de novo lipogenesis were assessed with proton
observed, carbon-13-edited MRS combined with 13C-labeled lipids and 13C-labeled
glucose, respectively. The molecular basis of alterations in hepatic liver
metabolism was analyzed in detail ex vivo using immunoblotting and targeted
quantitative proteomics. Both glucose and fructose feeding increased adiposity,
but only fructose induced hepatic lipid accumulation. In vivo MRS showed that
this was not caused by increased hepatic uptake of dietary lipids, but could be
attributed to an increase in de novo lipogenesis. Stimulation of lipogenesis by
fructose was confirmed by a strong upregulation of lipogenic enzymes, which was
more potent than with glucose. The non-caloric sweetener aspartame did not
significantly affect liver lipid content or metabolism. In conclusion, liquid
fructose more severely affected liver lipid metabolism in rats than glucose,
while aspartame had no effect.
PMID- 28489052
TI - Crude Ecklonia cava Flake Extracts Attenuate Inflammation through the Regulation
of TLR4 Signaling Pathway in LPS-Induced RAW264.7 Cells.
AB - We investigated the beneficial effects of the crude Ecklonia cava flake (CEF),
which is a residual product after polyphenol extraction from Ecklonia cava, on
inflammation in LPS-stimulated RAW264.7 cells. A group of five different CEF
extracts was obtained by a preparation process using water, hydrochloric acid or
temperature. We observed that large-size (>19 kDa) CEF extract, which was
extracted with water at 95 degrees C (CEF-W, 95 degrees C), suppressed the
production of inflammatory cytokines by inhibiting its mRNA expression in LPS
induced RAW264.7 cells. TLR4 signaling involvements were negatively regulated by
CEF-W, 95 degrees C. CEF-W, 95 degrees C repressed the translocation of NF
kappaB from cytoplasm into nucleus in LPS-induced RAW264.7 cells. CEF-W, 95
degrees C attenuated the phosphorylation of TBK1 and IRF3 by inhibiting the
phosphorylation of ERK. Taken together, we demonstrated that large-size CEF-W, 95
degrees C may act as a negative regulator of inflammation through the
suppression of TLR4 signaling constituents in LPS-induced RAW264.7 cells.
PMID- 28489054
TI - A Survey on an Energy-Efficient and Energy-Balanced Routing Protocol for Wireless
Sensor Networks.
AB - Wireless sensor networks (WSNs) form an important part of industrial application.
There has been growing interest in the potential use of WSNs in applications such
as environment monitoring, disaster management, health care monitoring,
intelligence surveillance and defence reconnaissance. In these applications, the
sensor nodes (SNs) are envisaged to be deployed in sizeable numbers in an
outlying area, and it is quite difficult to replace these SNs after complete
deployment in many scenarios. Therefore, as SNs are predominantly battery powered
devices, the energy consumption of the nodes must be properly managed in order to
prolong the network lifetime and functionality to a rational time. Different
energy-efficient and energy-balanced routing protocols have been proposed in
literature over the years. The energy-efficient routing protocols strive to
increase the network lifetime by minimizing the energy consumption in each SN. On
the other hand, the energy-balanced routing protocols protract the network
lifetime by uniformly balancing the energy consumption among the nodes in the
network. There have been various survey papers put forward by researchers to
review the performance and classify the different energy-efficient routing
protocols for WSNs. However, there seems to be no clear survey emphasizing the
importance, concepts, and principles of load-balanced energy routing protocols
for WSNs. In this paper, we provide a clear picture of both the energy-efficient
and energy-balanced routing protocols for WSNs. More importantly, this paper
presents an extensive survey of the different state-of-the-art energy-efficient
and energy-balanced routing protocols. A taxonomy is introduced in this paper to
classify the surveyed energy-efficient and energy-balanced routing protocols
based on their proposed mode of communication towards the base station (BS). In
addition, we classified these routing protocols based on the solution types or
algorithms, and the input decision variables defined in the routing algorithm.
The strengths and weaknesses of the choice of the decision variables used in the
design of these energy-efficient and energy-balanced routing protocols are
emphasised. Finally, we suggest possible research directions in order to optimize
the energy consumption in sensor networks.
PMID- 28489053
TI - Nasal Infection of Enterovirus D68 Leading to Lower Respiratory Tract
Pathogenesis in Ferrets (Mustela putorius furo).
AB - Data from EV-D68-infected patients demonstrate that pathological changes in the
lower respiratory tract are principally characterized by severe respiratory
illness in children and acute flaccid myelitis. However, lack of a suitable
animal model for EV-D68 infection has limited the study on the pathogenesis of
this critical pathogen, and the development of a vaccine. Ferrets have been
widely used to evaluate respiratory virus infections. In the current study, we
used EV-D68-infected ferrets as a potential animal to identify impersonal
indices, involving clinical features and histopathological changes in the upper
and lower respiratory tract (URT and LRT). The research results demonstrate that
the EV-D68 virus leads to minimal clinical symptoms in ferrets. According to the
viral load detection in the feces, nasal, and respiratory tracts, the infection
and shedding of EV-D68 in the ferret model was confirmed, and these results were
supported by the EV-D68 VP1 immunofluorescence confocal imaging with alpha2,6
linked sialic acid (SA) in lung tissues. Furthermore, we detected the
inflammatory cytokine/chemokine expression level, which implied high expression
levels of interleukin (IL)-1a, IL-8, IL-5, IL-12, IL-13, and IL-17a in the lungs.
These data indicate that systemic observation of responses following infection
with EV-D68 in ferrets could be used as a model for EV-D68 infection and
pathogenesis.
PMID- 28489055
TI - Substrate Dependent Ad-Atom Migration on Graphene and the Impact on Electron-Beam
Sculpting Functional Nanopores.
AB - The use of atomically thin graphene for molecular sensing has attracted
tremendous attention over the years and, in some instances, could displace the
use of classical thin films. For nanopore sensing, graphene must be suspended
over an aperture so that a single pore can be formed in the free-standing region.
Nanopores are typically drilled using an electron beam (e-beam) which is tightly
focused until a desired pore size is obtained. E-beam sculpting of graphene
however is not just dependent on the ability to displace atoms but also the
ability to hinder the migration of ad-atoms on the surface of graphene. Using
relatively lower e-beam fluxes from a thermionic electron source, the C-atom
knockout rate seems to be comparable to the rate of carbon ad-atom attraction and
accumulation at the e-beam/graphene interface (i.e., Rknockout ~ Raccumulation).
Working at this unique regime has allowed the study of carbon ad-atom migration
as well as the influence of various substrate materials on e-beam sculpting of
graphene. We also show that this information was pivotal to fabricating
functional graphene nanopores for studying DNA with increased spatial resolution
which is attributed to atomically thin membranes.
PMID- 28489056
TI - MERITXELL: The Multifrequency Experimental Radiometer with Interference Tracking
for Experiments over Land and Littoral-Instrument Description, Calibration and
Performance.
AB - MERITXELL is a ground-based multisensor instrument that includes a multiband dual
polarization radiometer, a GNSS reflectometer, and several optical sensors. Its
main goals are twofold: to test data fusion techniques, and to develop Radio
Frequency Interference (RFI) detection, localization and mitigation techniques.
The former is necessary to retrieve complementary data useful to develop
geophysical models with improved accuracy, whereas the latter aims at solving one
of the most important problems of microwave radiometry. This paper describes the
hardware design, the instrument control architecture, the calibration of the
radiometer, and several captures of RFI signals taken with MERITXELL in urban
environment. The multiband radiometer has a dual linear polarization total-power
radiometer topology, and it covers the L-, S-, C-, X-, K-, Ka-, and W-band. Its
back-end stage is based on a spectrum analyzer structure which allows to perform
real-time signal processing, while the rest of the sensors are controlled by a
host computer where the off-line processing takes place. The calibration of the
radiometer is performed using the hot-cold load procedure, together with the
tipping curves technique in the case of the five upper frequency bands. Finally,
some captures of RFI signals are shown for most of the radiometric bands under
analysis, which evidence the problem of RFI in microwave radiometry, and the
limitations they impose in external calibration.
PMID- 28489057
TI - An Optimized Facile Procedure to Synthesize and Purify Allicin.
AB - Allicin is a reactive sulfur species (RSS) and defence substance from garlic
(Allium sativum L.). The compound is a broad-spectrum antibiotic that is also
effective against multiple drug resistant (MDR) strains. A detailed protocol for
allicin synthesis based on diallyl-disulfide (DADS) oxidation by H2O2 using
acetic acid as a catalyst was published in 2001 by Lawson and Wang. Here we
report on improvements to this basic method, clarify the mechanism of the
reaction and show that it is zero-order with respect to DADS and first-order with
respect to the concentration of H2O2. The progress of allicin synthesis and the
reaction mechanism were analyzsd by high-performance liquid chromatography (HPLC)
and the identity and purity of the products was verified with LC-MS and 1H-NMR.
We were able to obtain allicin of high purity (>98%) and >91% yield, with
standard equipment available in any reasonable biological laboratory. This
protocol will enable researchers to prepare and work with easily and cheaply
prepared allicin of high quality.
PMID- 28489058
TI - The Neuroprotective Effects of Phenolic Acids: Molecular Mechanism of Action.
AB - The neuroprotective role of phenolic acids from food has previously been reported
by many authors. In this review, the role of phenolic acids in ameliorating
depression, ischemia/reperfusion injury, neuroinflammation, apoptosis, glutamate
induced toxicity, epilepsy, imbalance after traumatic brain injury,
hyperinsulinemia-induced memory impairment, hearing and vision disturbances,
Parkinson's disease, Huntington's disease, anti-amyotrophic lateral sclerosis,
Chagas disease and other less distributed diseases is discussed. This review
covers the in vitro, ex vivo and in vivo studies concerning the prevention and
treatment of neurological disorders (on the biochemical and gene expression
levels) by phenolic acids.
PMID- 28489059
TI - The Impact of Diet Wheat Source on the Onset of Type 1 Diabetes Mellitus-Lessons
Learned from the Non-Obese Diabetic (NOD) Mouse Model.
AB - Nutrition, especially wheat consumption, is a major factor involved in the onset
of type 1 diabetes (T1D) and other autoimmune diseases such as celiac. While
modern wheat cultivars possess similar gliadin proteins associated with the onset
of celiac disease and T1D, alternative dietary wheat sources from Israeli
landraces and native ancestral species may be lacking the epitopes linked with
T1D, potentially reducing the incidence of T1D. The Non-Obese Diabetic (NOD)
mouse model was used to monitor the effects of dietary wheat sources on the onset
and development of T1D. The effects of modern wheat flour were compared with
those from either T. aestivum, T. turgidum spp. dicoccoides, or T. turgidum spp.
dicoccum landraces or a non-wheat diet. Animals which received wheat from local
landraces or ancestral species such as emmer displayed a lower incidence of T1D
and related complications compared to animals fed a modern wheat variety. This
study is the first report of the diabetogenic properties of various dietary wheat
sources and suggests that alternative dietary wheat sources may lack T1D linked
epitopes, thus reducing the incidence of T1D.
PMID- 28489060
TI - The Effect of VPA on Increasing Radiosensitivity in Osteosarcoma Cells and
Primary-Culture Cells from Chemical Carcinogen-Induced Breast Cancer in Rats.
AB - This study explored whether valproic acid (VPA, a histone deacetylase inhibitor)
could radiosensitize osteosarcoma and primary-culture tumor cells, and determined
the mechanism of VPA-induced radiosensitization. The working system included
osteosarcoma cells (U2OS) and primary-culture cells from chemical carcinogen
(DMBA)-induced breast cancer in rats; and clonogenic survival,
immunofluorescence, fluorescent in situ hybridization (FISH) for chromosome
aberrations, and comet assays were used in this study. It was found that VPA at
the safe or critical safe concentration of 0.5 or 1.0 mM VPA could result in the
accumulation of more ionizing radiation (IR)-induced DNA double strand breaks,
and increase the cell radiosensitivity. VPA-induced radiosensitivity was
associated with the inhibition of DNA repair activity in the working systems. In
addition, the chromosome aberrations including chromosome breaks, chromatid
breaks, and radial structures significantly increased after the combination
treatment of VPA and IR. Importantly, the results obtained by primary-culture
cells from the tissue of chemical carcinogen-induced breast cancer in rats
further confirmed our findings. The data in this study demonstrated that VPA at a
safe dose was a radiosensitizer for osteosarcoma and primary-culture tumor cells
through suppressing DNA-double strand breaks repair function.
PMID- 28489062
TI - Ultrasound Transmission Tomography for Detecting and Measuring Cylindrical
Objects Embedded in Concrete.
AB - This study explores the feasibility of using transmission tomographic images
based on attenuation measures in transmission to detect and estimate the most
common materials that are embedded in concrete, reinforcements and natural and
artificial voids. A limited set of concrete specimens have been made in which
cylindrical objects such as bars/tubes of steel, PVC and aluminium have been
embedded to analyse the effect of size and material. The methodology and scope of
this study is presented and numerical simulations are carried out to optimize the
emitter-receiver configuration and to understand the complex physical propagation
phenomena of ultrasonic signals that travel through concrete with embedded
inclusions. Experimental tomographic images are obtained by using an ultrasonic
tomographic system, which has the advantage of needing only two ultrasonic
transducers. Both the software simulation tool and the tomographic inspection
system are developed by the authors. The obtained results show that PVC tubes and
steel bars of diameters higher than 19 mm and embedded in cylindrical specimens,
can be detected and their sizes estimated using segmented tomographic images.
PMID- 28489061
TI - Microbial Natural Product Alternariol 5-O-Methyl Ether Inhibits HIV-1 Integration
by Blocking Nuclear Import of the Pre-Integration Complex.
AB - While Highly Active Antiretroviral Therapy (HAART) has significantly decreased
the mortality of human immunodeficiency virus (HIV)-infected patients, emerging
drug resistance to approved HIV-1 integrase inhibitors highlights the need to
develop new antivirals with novel mechanisms of action. In this study, we
screened a library of microbial natural compounds from endophytic fungus
Colletotrichum sp. and identified alternariol 5-O-methyl ether (AME) as a
compound that inhibits HIV-1 pre-integration steps. Time-of addition analysis,
quantitative real-time PCR, confocal microscopy, and WT viral replication assay
were used to elucidate the mechanism. As opposed to the approved integrase
inhibitor Raltegravir, AME reduced both the integrated viral DNA and the 2-long
terminal repeat (2-LTR) circular DNA, which suggests that AME impairs the nuclear
import of viral DNA. Further confocal microscopy studies showed that AME
specifically blocks the nuclear import of HIV-1 integrase and pre-integration
complex without any adverse effects on the importin alpha/beta and importin beta
mediated nuclear import pathway in general. Importantly, AME inhibited
Raltegravir-resistant HIV-1 strains and exhibited a broad anti-HIV-1 activity in
diverse cell lines. These data collectively demonstrate the potential of AME for
further development into a new HIV inhibitor, and suggest the utility of viral
DNA nuclear import as a target for anti-HIV drug discovery.
PMID- 28489064
TI - An Interference Mitigation Scheme of Device-to-Device Communications for Sensor
Networks Underlying LTE-A.
AB - Device-to-Device (D2D) communication technology has become a key factor in
wireless sensor networks to form autonomous communication links among sensor
nodes. Many research results for D2D have been presented to resolve different
technical issues of D2D. Nevertheless, the previous works have not resolved the
shortage of data rate and limited coverage of wireless sensor networks. Due to
bandwidth shortages and limited communication coverage, 3rd Generation
Partnership Project (3GPP) has introduced a new Device-to-Device (D2D)
communication technique underlying cellular networks, which can improve spectral
efficiencies by enabling the direct communication of devices in proximity without
passing through enhanced-NodeB (eNB). However, to enable D2D communication in a
cellular network presents a challenge with regard to radio resource management
since D2D links reuse the uplink radio resources of cellular users and it can
cause interference to the receiving channels of D2D user equipment (DUE). In this
paper, a hybrid mechanism is proposed that uses Fractional Frequency Reuse (FFR)
and Almost Blank Sub-frame (ABS) schemes to handle inter-cell interference caused
by cellular user equipments (CUEs) to D2D receivers (DUE-Rxs), reusing the same
resources at the cell edge area. In our case, DUE-Rxs are considered as victim
nodes and CUEs as aggressor nodes, since our primary target is to minimize inter
cell interference in order to increase the signal to interference and noise ratio
(SINR) of the target DUE-Rx at the cell edge area. The numerical results show
that the interference level of the target D2D receiver (DUE-Rx) decreases
significantly compared to the conventional FFR at the cell edge. In addition, the
system throughput of the proposed scheme can be increased up to 60% compared to
the conventional FFR.
PMID- 28489063
TI - African Swine Fever Virus: A Review.
AB - African swine fever (ASF) is a highly contagious viral disease of swine which
causes high mortality, approaching 100%, in domestic pigs. ASF is caused by a
large, double stranded DNA virus, ASF virus (ASFV), which replicates
predominantly in the cytoplasm of macrophages and is the only member of the
Asfarviridae family, genus Asfivirus. The natural hosts of this virus include
wild suids and arthropod vectors of the Ornithodoros genus. The infection of ASFV
in its reservoir hosts is usually asymptomatic and develops a persistent
infection. In contrast, infection of domestic pigs leads to a lethal hemorrhagic
fever for which there is no effective vaccine. Identification of ASFV genes
involved in virulence and the characterization of mechanisms used by the virus to
evade the immune response of the host are recognized as critical steps in the
development of a vaccine. Moreover, the interplay of the viral products with host
pathways, which are relevant for virus replication, provides the basic
information needed for the identification of potential targets for the
development of intervention strategies against this disease.
PMID- 28489065
TI - Sound Source Localization Using Non-Conformal Surface Sound Field Transformation
Based on Spherical Harmonic Wave Decomposition.
AB - Spherical microphone arrays have been paid increasing attention for their ability
to locate a sound source with arbitrary incident angle in three-dimensional
space. Low-frequency sound sources are usually located by using spherical near
field acoustic holography. The reconstruction surface and holography surface are
conformal surfaces in the conventional sound field transformation based on
generalized Fourier transform. When the sound source is on the cylindrical
surface, it is difficult to locate by using spherical surface conformal
transform. The non-conformal sound field transformation by making a transfer
matrix based on spherical harmonic wave decomposition is proposed in this paper,
which can achieve the transformation of a spherical surface into a cylindrical
surface by using spherical array data. The theoretical expressions of the
proposed method are deduced, and the performance of the method is simulated.
Moreover, the experiment of sound source localization by using a spherical array
with randomly and uniformly distributed elements is carried out. Results show
that the non-conformal surface sound field transformation from a spherical
surface to a cylindrical surface is realized by using the proposed method. The
localization deviation is around 0.01 m, and the resolution is around 0.3 m. The
application of the spherical array is extended, and the localization ability of
the spherical array is improved.
PMID- 28489066
TI - Two Single Nucleotide Polymorphisms (rs2431697 and rs2910164) of miR-146a Are
Associated with Risk of Coronary Artery Disease.
AB - The coronary artery disease (CAD) is one of the most severe cardiovascular
diseases. MicroRNA-146a (miR-146a) influences the pathology of cardiovascular
diseases. Two single nucleotide polymorphisms (SNPs) of miR-146a (rs2431697 and
rs2910164) have been reported to alter the function or expression of microRNA.
The purpose of this study is to evaluate the association between miR-146a gene
polymorphism and the risk of CAD in the Chinese population. A total of 353 CAD
patients and 368 controls were recruited, and SNPs were analyzed by the matrix
assisted laser desorption/ionization time-of-flight mass spectrometry and
Sequenom MassARRAY system. The gene frequencies of rs2431697 and rs2910164 were
significantly different between the two groups. The mutant type (T allele) of
rs2431697 and wild type (C allele) of rs2910164 were more frequent in CAD
patients. T allele carriers in rs2431697 had an increased CAD risk, while G
allele of rs2910164 decreased the risk of CAD significantly. In conclusion, we
found that the T allele of rs2431697 was a risk factor of CAD in the Chinese
population. Meanwhile, we demonstrated that the G allele of rs2910164 decreased
the susceptibility of CAD.
PMID- 28489067
TI - A Study Protocol for Applying User Participation and Co-Learning-Lessons Learned
from the eBalance Project.
AB - The eBalance project is based on the idea that serious exergames-i.e., computer
gaming systems with an interface that requires physical exertion to play-that are
well adapted to users, can become a substantial part of a solution to recognized
problems of insufficient engagement in fall-prevention exercise and the high
levels of fall-related injuries among older people. This project is carried out
as a collaboration between eight older people who have an interest in balance
training and met the inclusion criteria of independence in personal activities of
daily living, access to and basic knowledge of a computer, four staff working
with the rehabilitation of older adults, and an interdisciplinary group of six
research coordinators covering the areas of geriatric care and rehabilitation, as
well as information technology and computer science. This paper describes the
study protocol of the project's initial phase which aims to develop a working
partnership with potential users of fall-prevention exergames, including its
conceptual underpinnings. The qualitative methodology was inspired by an
ethnographical approach implying combining methods that allowed the design to
evolve through the study based on the participants' reflections. A participatory
and appreciative action and reflection (PAAR) approach, accompanied by inquiries
inspired by the Normalization Process Theory (NPT) was used in interactive
workshops, including exergame testing, and between workshop activities. Data were
collected through audio recordings, photos, and different types of written
documentation. The findings provide a description of the methodology thus
developed and applied. They display a methodology that can be useful for the
design and development of care service and innovations for older persons where
user participation is in focus.
PMID- 28489068
TI - TNFalpha drives mitochondrial stress in POMC neurons in obesity.
AB - Consuming a calorically dense diet stimulates microglial reactivity in the
mediobasal hypothalamus (MBH) in association with decreased number of appetite
curbing pro-opiomelanocortin (POMC) neurons; whether the reduction in POMC
neuronal function is secondary to the microglial activation is unclear. Here we
show that in hypercaloric diet-induced obese mice, persistently activated
microglia in the MBH hypersecrete TNFalpha that in turn stimulate mitochondrial
ATP production in POMC neurons, promoting mitochondrial fusion in their neurites,
and increasing POMC neuronal firing rates and excitability. Specific disruption
of the gene expressions of TNFalpha downstream signals TNFSF11A or NDUFAB1 in the
MBH of diet-induced obese mice reverses mitochondrial elongation and reduces
obesity. These data imply that in a hypercaloric environment, persistent
elevation of microglial reactivity and consequent TNFalpha secretion induces
mitochondrial stress in POMC neurons that contributes to the development of
obesity.
PMID- 28489069
TI - Histone variant H2A.J accumulates in senescent cells and promotes inflammatory
gene expression.
AB - The senescence of mammalian cells is characterized by a proliferative arrest in
response to stress and the expression of an inflammatory phenotype. Here we show
that histone H2A.J, a poorly studied H2A variant found only in mammals,
accumulates in human fibroblasts in senescence with persistent DNA damage. H2A.J
also accumulates in mice with aging in a tissue-specific manner and in human
skin. Knock-down of H2A.J inhibits the expression of inflammatory genes that
contribute to the senescent-associated secretory phenotype (SASP), and over
expression of H2A.J increases the expression of some of these genes in
proliferating cells. H2A.J accumulation may thus promote the signalling of
senescent cells to the immune system, and it may contribute to chronic
inflammation and the development of aging-associated diseases.
PMID- 28489070
TI - Senescent tumor cells lead the collective invasion in thyroid cancer.
AB - Cellular senescence has been perceived as a barrier against carcinogenesis.
However, the senescence-associated secretory phenotype (SASP) of senescent cells
can promote tumorigenesis. Here, we show senescent tumour cells are frequently
present in the front region of collective invasion of papillary thyroid carcinoma
(PTC), as well as lymphatic channels and metastatic foci of lymph nodes. In in
vitro invasion analysis, senescent tumour cells exhibit high invasion ability as
compared with non-senescent tumour cells through SASP expression. Collective
invasion in PTC is led by senescent tumour cells characterized by generation of a
C-X-C-motif ligand (CXCL)12 chemokine gradient in the front region. Furthermore,
senescent cells increase the survival of cancer cells via CXCL12/CXCR4
signalling. An orthotopic xenograft in vivo model also shows higher lymphatic
vessels involvement in the group co-transplanted with senescent cells and cancer
cells. These findings suggest that senescent cells are actively involved in the
collective invasion and metastasis of PTC.
PMID- 28489071
TI - Exchange pathways of plastoquinone and plastoquinol in the photosystem II
complex.
AB - Plastoquinone (PLQ) acts as an electron carrier between photosystem II (PSII) and
the cytochrome b6f complex. To understand how PLQ enters and leaves PSII, here we
show results of coarse grained molecular dynamics simulations of PSII embedded in
the thylakoid membrane, covering a total simulation time of more than 0.5 ms. The
long time scale allows the observation of many spontaneous entries of PLQ into
PSII, and the unbinding of plastoquinol (PLQol) from the complex. In addition to
the two known channels, we observe a third channel for PLQ/PLQol diffusion
between the thylakoid membrane and the PLQ binding sites. Our simulations point
to a promiscuous diffusion mechanism in which all three channels function as
entry and exit channels. The exchange cavity serves as a PLQ reservoir. Our
simulations provide a direct view on the exchange of electron carriers, a key
step of the photosynthesis machinery.
PMID- 28489072
TI - Antibody targeting intracellular oncogenic Ras mutants exerts anti-tumour effects
after systemic administration.
AB - Oncogenic Ras mutants, frequently detected in human cancers, are high-priority
anticancer drug targets. However, direct inhibition of oncogenic Ras mutants with
small molecules has been extremely challenging. Here we report the development of
a human IgG1 format antibody, RT11, which internalizes into the cytosol of living
cells and selectively binds to the activated GTP-bound form of various oncogenic
Ras mutants to block the interactions with effector proteins, thereby suppressing
downstream signalling and exerting anti-proliferative effects in a variety of
tumour cells harbouring oncogenic Ras mutants. When systemically administered, an
RT11 variant with an additional tumour-associated integrin binding moiety for
tumour tissue targeting significantly inhibits the in vivo growth of oncogenic
Ras-mutated tumour xenografts in mice, but not wild-type Ras-harbouring tumours.
Our results demonstrate the feasibility of developing therapeutic antibodies for
direct targeting of cytosolic proteins that are inaccessible using current
antibody technology.
PMID- 28489073
TI - Genetic diversity and gene flow decline with elevation in montane mayflies.
AB - Montane environments around the globe are biodiversity 'hotspots' and important
reservoirs of genetic diversity. Montane species are also typically more
vulnerable to environmental change than their low-elevation counterparts due to
restricted ranges and dispersal limitations. Here we focus on two abundant
congeneric mayflies (Baetis bicaudatus and B. tricaudatus) from montane streams
over an elevation gradient spanning 1400 m. Using single-nucleotide polymorphism
genotypes, we measured population diversity and vulnerability in these two
species by: (i) describing genetic diversity and population structure across
elevation gradients to identify mechanisms underlying diversification; (ii)
performing spatially explicit landscape analyses to identify environmental
drivers of differentiation; and (iii) identifying outlier loci hypothesized to
underlie adaptive divergence. Differences in the extent of population structure
in these species were evident depending upon their position along the elevation
gradient. Heterozygosity, effective population sizes and gene flow all declined
with increasing elevation, resulting in substantial population structure in the
higher elevation species (B. bicaudatus). At lower elevations, populations of
both species are more genetically similar, indicating ongoing gene flow.
Isolation by distance was detected at lower elevations only, whereas landscape
barriers better predicted genetic distance at higher elevations. At higher
elevations, dispersal was restricted due to landscape effects, resulting in
greater population isolation. Our results demonstrate differentiation over small
spatial scales along an elevation gradient, and highlight the importance of
preserving genetic diversity in more isolated high-elevation populations.
PMID- 28489074
TI - Analysis of renal cancer cell lines from two major resources enables genomics
guided cell line selection.
AB - The utility of cancer cell lines is affected by the similarity to endogenous
tumour cells. Here we compare genomic data from 65 kidney-derived cell lines from
the Cancer Cell Line Encyclopedia and the COSMIC Cell Lines Project to three
renal cancer subtypes from The Cancer Genome Atlas: clear cell renal cell
carcinoma (ccRCC, also known as kidney renal clear cell carcinoma), papillary
(pRCC, also known as kidney papillary) and chromophobe (chRCC, also known as
kidney chromophobe) renal cell carcinoma. Clustering copy number alterations
shows that most cell lines resemble ccRCC, a few (including some often used as
models of ccRCC) resemble pRCC, and none resemble chRCC. Human ccRCC tumours
clustering with cell lines display clinical and genomic features of more
aggressive disease, suggesting that cell lines best represent aggressive tumours.
We stratify mutations and copy number alterations for important kidney cancer
genes by the consistency between databases, and classify cell lines into
established gene expression-based indolent and aggressive subtypes. Our results
could aid investigators in analysing appropriate renal cancer cell lines.
PMID- 28489075
TI - Lipoprotein-biomimetic nanostructure enables efficient targeting delivery of
siRNA to Ras-activated glioblastoma cells via macropinocytosis.
AB - Hyperactivated Ras regulates many oncogenic pathways in several malignant human
cancers including glioblastoma and it is an attractive target for cancer
therapies. Ras activation in cancer cells drives protein internalization via
macropinocytosis as a key nutrient-gaining process. By utilizing this unique
endocytosis pathway, here we create a biologically inspired nanostructure that
can induce cancer cells to 'drink drugs' for targeting activating transcription
factor-5 (ATF5), an overexpressed anti-apoptotic transcription factor in
glioblastoma. Apolipoprotein E3-reconstituted high-density lipoprotein is used to
encapsulate the siRNA-loaded calcium phosphate core and facilitate it to
penetrate the blood-brain barrier, thus targeting the glioblastoma cells in a
macropinocytosis-dependent manner. The nanostructure carrying ATF5 siRNA exerts
remarkable RNA-interfering efficiency, increases glioblastoma cell apoptosis and
inhibits tumour cell growth both in vitro and in xenograft tumour models. This
strategy of targeting the macropinocytosis caused by Ras activation provides a
nanoparticle-based approach for precision therapy in glioblastoma and other Ras
activated cancers.
PMID- 28489076
TI - HLA-DP84Gly constitutively presents endogenous peptides generated by the class I
antigen processing pathway.
AB - Classical antigen processing leads to the presentation of antigenic peptides
derived from endogenous and exogenous sources for MHC class I and class II
molecules, respectively. Here we show that, unlike other class II molecules,
prevalent HLA-DP molecules with beta-chains encoding Gly84 (DP84Gly)
constitutively present endogenous peptides. DP84Gly does not bind invariant chain
(Ii) via the class II-associated invariant chain peptide (CLIP) region, nor does
it present CLIP. However, Ii does facilitate the transport of DP84Gly from the
endoplasmic reticulum (ER) to the endosomal/lysosomal pathway by transiently
binding DP84Gly via a non-CLIP region(s) in a pH-sensitive manner. Accordingly,
like class I, DP84Gly constitutively presents endogenous peptides processed by
the proteasome and transported to the ER by the transporter associated with
antigen processing (TAP). Therefore, DP84Gly, found only in common chimpanzees
and humans, uniquely uses both class I and II antigen-processing pathways to
present peptides derived from intracellular and extracellular sources.
PMID- 28489077
TI - Heterodimerization of Munc13 C2A domain with RIM regulates synaptic vesicle
docking and priming.
AB - The presynaptic active zone protein Munc13 is essential for neurotransmitter
release, playing key roles in vesicle docking and priming. Mechanistically, it is
thought that the C2A domain of Munc13 inhibits the priming function by
homodimerization, and that RIM disrupts the autoinhibitory homodimerization
forming monomeric priming-competent Munc13. However, it is unclear whether the
C2A domain mediates other Munc13 functions in addition to this inactivation
activation switch. Here, we utilize mutations that modulate the homodimerization
and heterodimerization states to define additional roles of the Munc13 C2A
domain. Using electron microscopy and electrophysiology in hippocampal cultures,
we show that the C2A domain is critical for additional steps of vesicular
release, including vesicle docking. Optimal vesicle docking and priming is only
possible when Munc13 heterodimerizes with RIM via its C2A domain. Beyond being a
switching module, our data suggest that the Munc13-RIM heterodimer is an active
component of the vesicle docking, priming and release complex.
PMID- 28489078
TI - Hybrid supercapacitors for reversible control of magnetism.
AB - Electric field tuning of magnetism is one of the most intensely pursued research
topics of recent times aiming at the development of new-generation low-power
spintronics and microelectronics. However, a reversible magnetoelectric effect
with an on/off ratio suitable for easy and precise device operation is yet to be
achieved. Here we propose a novel route to robustly tune magnetism via the
charging/discharging processes of hybrid supercapacitors, which involve
electrostatic (electric-double-layer capacitance) and electrochemical
(pseudocapacitance) doping. We use both charging mechanisms-occurring at the
La0.74Sr0.26MnO3/ionic liquid interface to control the balance between
ferromagnetic and non-ferromagnetic phases of La1-xSrxMnO3 to an unprecedented
extent. A magnetic modulation of up to ~33% is reached above room temperature
when applying an external potential of only about 2.0 V. Our case study intends
to draw attention to new, reversible physico-chemical phenomena in the rather
unexplored area of magnetoelectric supercapacitors.
PMID- 28489080
TI - ERRATUM: Medical morbidities and DNA methylation of NR3C1 in preterm infants.
PMID- 28489079
TI - TRPV1 channels are critical brain inflammation detectors and neuropathic pain
biomarkers in mice.
AB - The capsaicin receptor TRPV1 has been widely characterized in the sensory system
as a key component of pain and inflammation. A large amount of evidence shows
that TRPV1 is also functional in the brain although its role is still debated.
Here we report that TRPV1 is highly expressed in microglial cells rather than
neurons of the anterior cingulate cortex and other brain areas. We found that
stimulation of microglial TRPV1 controls cortical microglia activation per se and
indirectly enhances glutamatergic transmission in neurons by promoting
extracellular microglial microvesicles shedding. Conversely, in the cortex of
mice suffering from neuropathic pain, TRPV1 is also present in neurons affecting
their intrinsic electrical properties and synaptic strength. Altogether, these
findings identify brain TRPV1 as potential detector of harmful stimuli and a key
player of microglia to neuron communication.
PMID- 28489082
TI - Experimental test of photonic entanglement in accelerated reference frames.
AB - The unification of the theory of relativity and quantum mechanics is a long
standing challenge in contemporary physics. Experimental techniques in quantum
optics have only recently reached the maturity required for the investigation of
quantum systems under the influence of non-inertial motion, such as being held at
rest in gravitational fields, or subjected to uniform accelerations. Here, we
report on experiments in which a genuine quantum state of an entangled photon
pair is exposed to a series of different accelerations. We measure an
entanglement witness for g-values ranging from 30 mg to up to 30 g-under free
fall as well on a spinning centrifuge-and have thus derived an upper bound on the
effects of uniform acceleration on photonic entanglement.
PMID- 28489083
TI - Exploring biomolecular energy landscapes.
AB - The potential energy landscape perspective provides both a conceptual and a
computational framework for predicting, understanding and designing molecular
properties. In this Feature Article, we highlight some recent advances that
greatly facilitate structure prediction and analysis of global thermodynamics and
kinetics in proteins and nucleic acids. The geometry optimisation procedures, on
which these calculations are based, can be accelerated significantly using local
rigidification of selected degrees of freedom, and through implementations on
graphics processing units. Results of progressive local rigidification are first
summarised for trpzip1, including a systematic analysis of the heat capacity and
rearrangement rates. Benchmarks for all the essential optimisation procedures are
then provided for a variety of proteins. Applications are then illustrated from a
study of how mutation affects the energy landscape for a coiled-coil protein, and
for transitions in helix morphology for a DNA duplex. Both systems exhibit an
intrinsically multifunnel landscape, with the potential to act as biomolecular
switches.
PMID- 28489084
TI - Observation of crystalline changes of titanium dioxide during lithium insertion
by visible spectrum analysis.
AB - Real-time analysis of changes in the atomic environment of materials is a cutting
edge technology that is being used to explain reaction dynamics in many fields of
science. Previously, this kind of analysis was only possible using heavy
nucleonic equipment such as XANES and EXAFS, or Raman spectroscopy on a moderate
scale. Here, a new methodology is described that can be used to track changes in
crystalline developments during complex Li insertion reactions via the
observation of structural color. To be specific, the changes in atomic
crystalline and nanostructure are shown during Li insertion in a complex TiO2
polymorph. Structural color corresponds to the refractive indices of materials
originating from their atomic bonding nature and precise wave interferences in
accordance with their nanostructure. Therefore, this new analysis simultaneously
reveals changes in the nanostructure as well as changes in the atomic bonding
nature of materials.
PMID- 28489085
TI - Intrinsic and light-induced nonadiabatic phenomena in the NaI molecule.
AB - Nonadiabatic effects play a very important role in controlling chemical dynamical
processes. They are strongly related to avoided crossings (AC) or conical
intersections (CIs) which can either be present naturally or induced by classical
laser light in a molecular system. The latter are named as "light-induced avoided
crossings" (LIACs) and "light-induced conical intersections" (LICIs). By
performing one or two dimensional quantum dynamical calculations LIAC and LICI
situations can easily be created even in diatomic molecules. Applying such
calculations for the NaI molecule, which is a strongly coupled diatomic in field
free case, significant differences between the impact of the LIAC and LICI on the
ground state population dynamics were observed. Moreover, obtained results
undoubtedly demonstrate that the effect of the LIAC and LICI on the dynamics
strongly depends on the intensity and the frequency of the applied laser field as
well as the permanent dipole moments of the molecule.
PMID- 28489086
TI - Molecular dynamics approach to understand the denaturing effect of a millimolar
concentration of dodine on a lambda-repressor and counteraction by trehalose.
AB - Commonly used denaturants for protein denaturation are conventionally required in
high concentrations in order to produce their effects. In this study, a molecular
dynamics simulation of a mutated version of the N-terminal domain of a lambda
repressor is carried out in the presence of a 10 millimolar (mM) concentration of
dodine. Such a small concentration is found to be effective for denaturation of
the protein. Both electrostatic and van der Waals interactions (between protein
and dodine) play a role in the denaturation process and we observe more
denaturation at the terminal helices. Three different molar concentrations of
trehalose are used in order to check the counteraction against the action of
dodine. This study shows that 0.5 and 1.0 M trehalose are sufficient to
counteract the action of dodine. The study also sheds light on the fact that some
protein sites are more responsive to unfolding, which is evident from the helical
fractions of the terminal helices for different systems. The counteraction of
trehalose on dodine-induced protein denaturation is found to be due to the
replacement of some of the dodine molecules by trehalose molecules in the
solvation shell of the protein. Preferential solvation of dodine molecules by
trehalose molecules through hydrogen bonding interactions also plays a vital role
in stabilizing the native conformation of the protein in a high trehalose
concentration. Replacement of protein-dodine and protein-water hydrogen bonds by
protein-trehalose hydrogen bonds is also observed.
PMID- 28489087
TI - Hydrolysis of cephalexin and meropenem by New Delhi metallo-beta-lactamase: the
substrate protonation mechanism is drug dependent.
AB - Emergence of antibiotic resistance due to New Delhi metallo-beta-lactamase (NDM
1) bacterial enzymes is of great concern due to their ability to hydrolyze a wide
range of antibiotics. There are ongoing efforts to obtain the atomistic details
of the hydrolysis mechanism in order to develop inhibitors for NDM-1. In
particular, it remains elusive how drug molecules of different families of
antibiotics are hydrolyzed by NDM-1 in an efficient manner. Here we report the
detailed molecular mechanism of NDM-1 catalyzed hydrolysis of cephalexin, a
cephalosporin family drug, and meropenem, a carbapenem family drug. This study
employs molecular dynamics (MD) simulations using hybrid quantum
mechanical/molecular mechanical (QM/MM) methods at the density functional theory
(DFT) level, based on which reaction pathways and the associated free energies
are obtained. We find that the mechanism and the free energy barrier for the ring
opening step are the same for both the drug molecules, while the subsequent
protonation step differs. In particular, we observe that the mechanism of the
protonation step depends on the R2 group of the drug molecule. Our simulations
show that allylic carbon protonation occurs in the case of the cephalexin drug
molecule where Lys211 is the proton donor, and the proton transfer occurs via a
water chain formed (only) at the ring-opened intermediate structure. Based on the
free energy profiles, the overall kinetics of drug hydrolysis is discussed.
Finally, we show that the proposed mechanisms and free energy profiles could
explain various experimental observations.
PMID- 28489088
TI - CFA-4 - a fluorinated metal-organic framework with exchangeable interchannel
cations.
AB - The syntheses and crystal structures of the fluorinated linker 1,4-bis(3,5
bis(trifluoromethyl)-1H-pyrazole-4-yl)benzene (H2-tfpb; 1) and the novel metal
organic framework family M[CFA-4] (Coordination Framework Augsburg University-4),
M[Cu5(tfpb)3] (M = Cu(i), K, Cs, Ca(0.5)), are described. The ligand 1 is fully
characterized by single crystal X-ray diffraction, photoluminescence-, NMR-, IR
spectroscopy, and mass spectrometry. The copper(i)-containing MOF crystallizes in
the hexagonal crystal system within the chiral space group P6322 (no. 182) and
the unit cell parameters are as follows: a = 23.630(5) A, c = 41.390(5) A, V = 20
015(6) A3. M[CFA-4] features a porous 3-D structure constructed from pentanuclear
copper(i) secondary building units {Cu(pz)6}- (pz = pyrazolate). Cu(I)[CFA-4] is
fully characterized by synchrotron single crystal X-ray diffraction,
thermogravimetric analysis, variable temperature powder X-ray diffraction, IR
spectroscopy, photoluminescence and gas sorption measurements. Moreover, thermal
stability and gas sorption properties of K[CFA-4] and Cu(I)[CFA-4] are compared.
PMID- 28489089
TI - Microscale solid-state thermal diodes enabling ambient temperature thermal
circuits for energy applications.
AB - Thermal diodes, or devices that transport thermal energy asymmetrically,
analogous to electrical diodes, hold promise for thermal energy harvesting and
conservation, as well as for phononics or information processing. The junction of
a phase change material and phase invariant material can form a thermal diode;
however, there are limited constituent materials available for a given target
temperature, particularly near ambient. In this work, we demonstrate that a micro
and nanoporous polystyrene foam can house a paraffin-based phase change material,
fused to PMMA, to produce mechanically robust, solid-state thermal diodes capable
of ambient operation with Young's moduli larger than 11.5 MPa and 55.2 MPa above
and below the melting transition point, respectively. Moreover, the composites
show significant changes in thermal conductivity above and below the melting
point of the constituent paraffin and rectification that is well-described by our
previous theory and the Maxwell-Eucken model. Maximum thermal rectifications
range from 1.18 to 1.34. We show that such devices perform reliably enough to
operate in thermal diode bridges, dynamic thermal circuits capable of
transforming oscillating temperature inputs into single polarity temperature
differences - analogous to an electrical diode bridge with widespread
implications for transient thermal energy harvesting and conservation. Overall,
our approach yields mechanically robust, solid-state thermal diodes capable of
engineering design from a mathematical model of phase change and thermal
transport, with implications for energy harvesting.
PMID- 28489090
TI - Understanding doping strategies in the design of organic electrode materials for
Li and Na ion batteries: an electronic structure perspective.
AB - In this paper, we present a systematic study of the effects of p- and n-doping in
small molecules on the voltage and capacity of organic electrode materials for
electrochemical batteries. In particular, coronene, phenalene derivatives as well
as disodium terephthalate and related fused ring derivatives, representing often
used building blocks in organic electrode materials, are chosen as model systems.
We show that p-doping can drastically increase the binding strength to Li or Na
and is therefore an effective strategy to design organic electrode materials for
both lithium and sodium ion batteries. It could also be used to increase the
theoretical capacity. On the other hand, n-doping generally has a much smaller
effect on the voltage. The effects of n- and p-doping are rationalized based on
the analysis of changes they induce in the band structure as well as in the
molecular structure.
PMID- 28489091
TI - Role of missing carotenoid in reducing the fluorescence of single monomeric
photosystem II core complexes.
AB - The fluorescence of monomeric photosystem II core complexes (mPSIIcc) of the
cyanobacterium Thermosynechococcus elongatus, originating from redissolved
crystals, is investigated by using single-molecule spectroscopy (SMS) at 1.6 K.
The emission spectra of individual mPSIIcc are dominated by sharp zero-phonon
lines, showing the existence of different emitters compatible with the F685,
F689, and F695 bands reported formerly. The intensity of F695 is reduced in
single mPSIIcc as compared to single PSIIcc-dimers (dPSIIcc). Crystal structures
show that one of the beta-carotene (beta-Car) cofactors located at the monomer
monomer interface in dPSIIcc is missing in mPSIIcc. This beta-Car in dPSIIcc is
in van der Waals distance to chlorophyll (Chl) 17 in the CP47 subunit. We suggest
that this Chl contributes to the F695 emitter. A loss of beta-Car cofactors in
mPSIIcc preparations will lead to an increased lifetime of the triplet state of
Chl 17, which can explain the reduced singlet emission of F695 as observed in
SMS.
PMID- 28489092
TI - Reactivity studies of silylene [PhC(NtBu)2](C5Me5)Si - reactions with [M(COD)Cl]2
(M = Rh(i), Ir(i)), S, Se, Te, and BH3.
AB - The reactivity of recently introduced N-heterocyclic silylene
[PhC(NtBu)2](C5Me5)Si was evaluated. Three different reaction pathways were
studied: (1) coordination to a Lewis acid, (2) oxidation by chalcogenides, and
(3) coordination to transition metal complexes. The reaction of the silylene with
BH3 led to the adduct [PhC(NtBu)2](C5Me5)Si(BH)3. Oxidation with the elemental
chalcogens sulphur, selenium, and tellurium resulted in the corresponding
silicon(iv)-chalcogenide compounds [PhC(NtBu)2](C5Me5)SiS,
[PhC(NtBu)2](C5Me5)SiSe and [PhC(NtBu)2](C5Me5)SiTe. Treatment of the silylene
with dimeric group 9 transition metal complexes [Ir(COD)Cl]2 and [Rh(COD)Cl]2
gave square planar coordinated transition metal silylene complexes
[{PhC(NtBu)2}(C5Me5)Si-Rh(COD)(Cl)] and [{PhC(NtBu)2}(C5Me5)Si-Ir(COD)(Cl)].
PMID- 28489093
TI - MgAl layered double hydroxide/chitosan porous scaffolds loaded with PFTalpha to
promote bone regeneration.
AB - Poor bone formation remains a key risk factor associated with acellular scaffolds
that occurs in some bone defects, particularly in patients with metabolic bone
disorders and local osteoporosis. We herein fabricated for the first time layered
double hydroxide-chitosan porous scaffolds loaded with PFTalpha (LDH-CS-PFTalpha
scaffolds) as therapeutic bone scaffolds for the controlled release of PFTalpha
to enhance stem cell osteogenic differentiation and bone regeneration. The LDH-CS
scaffolds had three-dimensional interconnected macropores, and plate-like LDH
nanoparticles were uniformly dispersed within or on the CS films. The LDH-CS
scaffolds exhibited appropriate PFTalpha drug delivery due to hydrogen bonding
among LDH, CS and PFTalpha. In vitro functional studies demonstrated that the
PFTalpha molecules exhibited potent ability to induce osteogenesis of hBMSCs via
the GSK3beta/beta-catenin pathway, and the LDH-CS-PFTalpha scaffolds
significantly enhanced the osteogenic differentiation of hBMSCs. In vivo studies
revealed significantly increased repair and regeneration of bone tissue in
cranial defect model rats compared to control rats at 12 weeks post-implantation.
In conclusion, the LDH-CS-PFTalpha scaffolds exhibited excellent osteogenic
differentiation and bone regeneration capability and hold great potential for
applications in defined local bone regeneration.
PMID- 28489094
TI - Theoretical insights into the mechanism of ferroptosis suppression via
inactivation of a lipid peroxide radical by liproxstatin-1.
AB - Ferroptosis is a recently discovered iron-dependent form of non-apoptotic cell
death caused by the accumulation of membrane lipid peroxidation products, which
is involved in various pathological conditions of the brain, kidney, liver and
heart. A potent spiroquinoxalinamine derivative named liproxstatin-1 is
discovered by high-throughput screening, which is able to suppress ferroptosis
via lipid peroxide scavenging in vivo. Thus, molecular simulations, density
functional theory (DFT) and variational transition-state theory with a small
curvature tunneling (SCT) coefficient are utilized to elucidate the detailed
mechanisms of inactivation of a lipid peroxide radical by liproxstatin-1. H-atom
abstracted from liproxstatin-1 by a CH3OO radical occurs preferentially at the
aromatic amine site (1'-NH) under thermodynamic and frontier molecular orbital
analysis. The value of a calculated rate constant at 300 K is up to 6.38 * 103 M
1 S-1, indicating that the quantum tunneling effect is responsible for making a
free radical trapping reaction more efficient by liproxstatin-1. The production
of a liproxstatin-1 radical is easily regenerated to the active reduced form by
ubiquinol in the body to avoid secondary damage by free radicals. A benzene ring
and the higher HOMO energy are beneficial to enhance the lipid radical scavenging
activity based on the structure-activity relationship study. Overall, the present
results provide theoretical insights into the exploration of novel ferroptosis
inhibitors.
PMID- 28489095
TI - Metrology of DNA arrays by super-resolution microscopy.
AB - Recent results in the assembly of DNA into structures and arrays with nanoscale
features and patterns have opened the possibility of using DNA for sub-10 nm
lithographic patterning of semiconductor devices. Super-resolution microscopy is
being actively developed for DNA-based imaging and is compatible with inline
optical metrology techniques for high volume manufacturing. Here, we combine DNA
tile assembly with state-dependent super-resolution microscopy to introduce
crystal-PAINT as a novel approach for metrology of DNA arrays. Using this
approach, we demonstrate optical imaging and characterization of DNA arrays
revealing grain boundaries and the temperature dependence of array quality. For
finite arrays, analysis of crystal-PAINT images provides further quantitative
information of array properties. This metrology approach enables defect detection
and classification and facilitates statistical analysis of self-assembled DNA
nanostructures.
PMID- 28489096
TI - Physical principles for DNA tile self-assembly.
AB - DNA tiles provide a promising technique for assembling structures with nanoscale
resolution through self-assembly by basic interactions rather than top-down
assembly of individual structures. Tile systems can be programmed to grow based
on logical rules, allowing for a small number of tile types to assemble large,
complex assemblies that can retain nanoscale resolution. Such algorithmic systems
can even assemble different structures using the same tiles, based on inputs that
seed the growth. While programming and theoretical analysis of tile self-assembly
often makes use of abstract logical models of growth, experimentally implemented
systems are governed by nanoscale physical processes that can lead to very
different behavior, more accurately modeled by taking into account the
thermodynamics and kinetics of tile attachment and detachment in solution. This
review discusses the relationships between more abstract and more physically
realistic tile assembly models. A central concern is how consideration of model
differences enables the design of tile systems that robustly exhibit the desired
abstract behavior in realistic physical models and in experimental
implementations. Conversely, we identify situations where self-assembly in
abstract models can not be well-approximated by physically realistic models,
putting constraints on physical relevance of the abstract models. To facilitate
the discussion, we introduce a unified model of tile self-assembly that clarifies
the relationships between several well-studied models in the literature.
Throughout, we highlight open questions regarding the physical principles for DNA
tile self-assembly.
PMID- 28489097
TI - Self-assembly of inverse patchy colloids with tunable patch coverage.
AB - We report a simple and scalable technique for the preparation of patchy particles
with tunable patch coverage. These particles are categorized as inverse patchy
colloidal particles (IPCs) as the patches repel each other while patch and non
patch surfaces attract. We demonstrate the effect of patch coverage,
concentration of electrolyte and concentration of particles on the self-assembly
of IPC particles. The study identifies various clustering zones such as (1)
finite-sized clusters, (2) chain-like assemblies and (3) irregular amorphous
aggregates. The linear assemblies are observed over a wide range of particle
concentrations and salt concentrations. The anisotropic electrostatic interaction
controls the formation of chain-like assemblies. In an extended study, we use
negatively charged isotropic colloidal (NCIC) particles to tune the self-assembly
of IPC particles. Interestingly, we observe significant improvement in the
clustering efficiency of IPC particles leading to the formation of co-polymeric,
flexible branched chains. Depending on the number ratio of NCIC particles with
respect to IPC particles, the clustering process is classified into three
different phases such as (1) finite-sized, (2) linear and (3) dispersed state.
Using a quantitative analysis we show that such evolution of structures is
attributed to seeding and crowding effects caused by the addition of NCIC
particles. The use of NCIC particles thus control the self-assembly of inverse
patchy colloids and tune the number and shape of the self-assembled structures.
PMID- 28489098
TI - Correction: Distinctive hippocampal zinc distribution patterns following stress
exposure in an animal model of PTSD.
AB - Correction for 'Distinctive hippocampal zinc distribution patterns following
stress exposure in an animal model of PTSD' by Hagit Sela et al., Metallomics,
2017, 9, 323-333.
PMID- 28489099
TI - Dual-core star-shaped single white polymers: the effect of host structure on
luminescence properties.
AB - The non-emissive benzene ring and green-emissive arylmaleimide are employed as
two independent cores to construct dual-core white star-shaped polymers (DC
PFMs). Due to the totally star-shaped structure, DC-PFMs display a higher quantum
yield and electroluminescence efficiency for a more efficient energy transfer
from the host to the guest than traditional single-core polymers (SC-PFMs).
PMID- 28489100
TI - A copper-phosphonate network as a high-performance heterogeneous catalyst for the
CO2 cycloaddition reactions and alcoholysis of epoxides.
AB - A novel 3D copper-phosphonate network, with the general formula
Cu7(H1L)2(TPT)3(H2O)6, namely compound 1, has been synthesized using a rigid
tetrahedral linker tetraphenylsilane tetrakis-4-phosphonic acid (H8L) and a
nitrogen-containing ancillary ligand (TPT: [5-(4-(1H-1,2,4-triazol-1-yl)phenyl)
1H-tetrazole]) under hydrothermal conditions. The compound was fully
characterized using PXRD, ICP, IR, TGA and elemental analysis. Compound 1 can be
used as an efficient catalyst for the CO2 coupling reaction that is greatly
superior to many conventional MOF-based catalysts, where porosity is always
mentioned and used. In addition, it shows excellent catalytic performance for
ring-opening reactions with epoxides under ambient conditions. Additionally,
compound 1 can be recycled at least three times without a significant compromise
in the activity in the two catalytic reactions.
PMID- 28489101
TI - Direct experimental observation of mesoscopic fluorous domains in fluorinated
room temperature ionic liquids.
AB - Fluorinated room temperature ionic liquids (FRTILs) represent a class of solvent
media that are attracting great attention due to their IL-specific properties as
well as features stemming from their fluorous nature. Medium-to-long fluorous
tails constitute a well-defined apolar moiety in the otherwise polar environment.
Similarly to the case of alkyl tails, such chains are expected to result in the
formation of self-assembled fluorous domains. So far, however, no direct
experimental observation has been made of the existence of such structural
heterogeneities on the nm scale. We report here the first experimental evidence
of the existence of mesoscopic spatial segregation of fluorinated domains, on the
basis of highly complementary X-ray and neutron scattering data sets
(highlighting the importance of the latter probe) and NMR spectroscopy. Data are
interpreted using atomistic molecular dynamics simulations, emphasizing the
existence of a self-assembly mechanism that delivers segregated fluorous domains,
where preferential solubilisation of fluorinated compounds can occur, thus paving
the way for several smart applications.
PMID- 28489102
TI - Temperature-modulated crystal growth and performance for highly reproducible and
efficient perovskite solar cells.
AB - The annealing temperature (Ta) effect on CH3NH3PbI3 perovskite solar cells (PSCs)
was studied. By utilizing a two-step technique, the Ta dependences of the optical
absorption, grain size, and crystallinity of a CH3NH3PbI3 thin film have been
revealed. It is found that the grain size of the CH3NH3PbI3 film increases
monotonically with Ta. Meanwhile, the decomposed PbI2 emerges when Ta exceeds 120
degrees C and its content increases rapidly as Ta increases further.
Consequently, the optical absorption of the CH3NH3PbI3 film and the efficiency of
PSCs reach their maximum at Ta = 120 degrees C simultaneously. The highest and
average device performances of PSCs achieved via this method are 17.61% and
16.40%, respectively. These results confirm the key role played by temperature
and provide a route to the performance-optimization of PSCs.
PMID- 28489103
TI - Triethanolamine doped multilayer MoS2 field effect transistors.
AB - Chemical doping has been investigated as an alternative method of conventional
ion implantation for two-dimensional materials. We herein report chemically doped
multilayer molybdenum disulfide (MoS2) field effect transistors (FETs) through n
type channel doping, wherein triethanolamine (TEOA) is used as an n-type dopant.
As a result of the TEOA doping process, the electrical performances of multilayer
MoS2 FETs were enhanced at room temperature. Extracted field effect mobility was
estimated to be ~30 cm2 V-1 s-1 after the surface doping process, which is 10
times higher than that of the pristine device. Subthreshold swing and contact
resistance were also improved after the TEOA doping process. The enhancement of
the subthreshold swing was demonstrated by using an independent FET model.
Furthermore, we found that the doping level can be effectively controlled by the
heat treatment method. These results demonstrate a promising material system that
is easily controlled with high performance, while elucidating the underlying
mechanism of improved electrical properties by the doping effect in a
multilayered scheme.
PMID- 28489104
TI - Spatially-resolved profiling of carbon nanotube uptake across cell lines.
AB - The internalisation and intra-cellular distribution of carbon nanotubes (CNT) has
been quantitatively assessed using imaging flow cytometry. Spatial analysis of
the bright field images indicates the presence of a small sub-population (5% of
cells) in which the internalised CNTs are packed into pronounced clusters,
visible as dark spots due to strong optical scattering by the nanotubes. The area
of these spots can be used as a label-free metric of CNT dose and we assess the
relative uptake of charge-neutral CNTs, over a 24 hours exposure period across
four cell types: J774 mouse macrophage cells, A549 and Calu-6 human lung cancer
cells, and MCF-7 human breast cells. The relative dose as indicated by the spot
area metric closely correlates to results using the same CNT preparation,
conjugated to a FITC-label and shows pronounced uptake by the J774 cells leading
to a mean dose that is >60% higher than for the other cell types. Spatial
evaluation of dosing clusters is also used to quantify differences in uptake by
J774 cells of CNTs with different surface functionalisation. While the percentage
of CNT-cluster positive cells increases from 5% to 19% when switching from charge
neutral CNTs to poly-cationic, dendron functionalised CNTs, the single cell level
analysis of internalised clusters indicates a lower dose per cell of poly
cationic CNTs relative to the charge-neutral CNTs. We concluded that there is
dose homeostasis i.e., the population-averaged cellular dose of CNTs remained
unchanged.
PMID- 28489105
TI - Chirality as a tool for function in porous organic cages.
AB - The control of solid state assembly for porous organic cages is more challenging
than for extended frameworks, such as metal-organic frameworks. Chiral
recognition is one approach to achieving this control. Here we investigate chiral
analogues of cages that were previously studied as racemates. We show that chiral
cages can be produced directly from chiral precursors or by separating racemic
cages by co-crystallisation with a second chiral cage, opening up a route to
producing chiral cages from achiral precursors. These chiral cages can be
cocrystallized in a modular, 'isoreticular' fashion, thus modifying porosity,
although some chiral pairings require a specific solvent to direct the crystal
into the desired packing mode. Certain cages are shown to interconvert chirality
in solution, and the steric factors governing this behavior are explored both by
experiment and by computational modelling.
PMID- 28489106
TI - Quantitative relationship between fluid inhomogeneities and flow enhancement in
nanotubes.
AB - Flow enhancement in nanotubes is of great potential to achieve ultra-fast fluidic
transport. However, the mechanism of such a fast transport and the reduction as
the tube enlarges to bulk scale is still unclear. In this study, we establish a
model to quantitatively correlate the flow enhancement and the fluid
inhomogeneity to describe the enhanced transport and its evolution with the tube
dimension. We found the fluid inhomogeneity at the solid-liquid interface in
nanotubes and its independence with tube size by dissipative particle dynamics
(DPD) simulation. Based on that, we establish novel theoretical models for the
penetration rate in nanotubes for the first time with parameters related to the
fluid inhomogeneity which can achieve quantitative prediction of nanoflow
enhancement and are valid through all scales.
PMID- 28489107
TI - A novel metal-free method for the selenocyanation of aromatic ketones to afford
alpha-carbonyl selenocyanates.
AB - A new method has been developed for the selenocyanation of aromatic ketones. This
reaction avoids the need to use pre-prepared alpha-halo ketones, providing rapid
access to alpha-carbonyl selenocyanates. We also investigated the mechanism for
this reaction and found that it proceeds via sequential radical iodination and
nucleophilic substitution reactions.
PMID- 28489109
TI - Statistical theory of polarizable target compound impregnation into a polymer
coil under the influence of an electric field.
AB - The paper presents a theoretical approach for describing the influence of an
electric field on the conformation of an electrically neutral dielectric polymer
chain dissolved in a dielectric solvent with an admixture of a target compound.
Each monomer and each molecule of the target compound carries positive excess
polarizability and the solvent is described as a continuous dielectric medium.
The model is based on the Flory-type mean-field theory. We demonstrate non
monotonic dependences of the expansion factor and the concentration of the target
compound on the strength of the electric field and molecular polarizability.
Namely, the target compound concentration in the internal polymer volume as a
function of electric field strength has pronounced maxima if the molecules are
polarizable. In addition, the expansion factor of the non-polarizable polymer
chain can be controlled by the electric field. The dependences of the expansion
factor and target compound concentration on the monomer polarizability exhibit
minima and intersection points. The intersection points correspond to the
equality of dielectric permittivities in the bulk solution and in the internal
polymer volume.
PMID- 28489111
TI - Layer-dependent electronic properties of phosphorene-like materials and
phosphorene-based van der Waals heterostructures.
AB - Black phosphorus is a layered semiconducting allotrope of phosphorus with high
carrier mobility. Its monolayer form, phosphorene, is an extremely fashionable
two-dimensional material which has promising potential in transistors,
optoelectronics and electronics. However, phosphorene-like analogues, especially
phosphorene-based heterostructures and their layer-controlled electronic
properties, are rarely systematically investigated. In this paper, the layer
dependent structural and electronic properties of phosphorene-like materials,
i.e., mono- and few-layer MXs (M = Sn, Ge; X = S, Se), are first studied via
first-principles calculations, and then the band edge position of these MXs as
well as mono- and few-layer phosphorene are aligned. It is revealed that van der
Waals heterostructures with a Moire superstructure formed by mutual coupling
among MXs and among MXs and few-layer phosphorene are able to show type-I or type
II characteristics and a I-II or II-I transition can be induced by adjusting the
number of layers. Our work is expected to yield a new family of phosphorene-based
semiconductor heterostructures with tunable electronic properties through
altering the number of layers of the composite.
PMID- 28489112
TI - An efficient charge separation and photocurrent generation in the carbon dot-zinc
oxide nanoparticle composite.
AB - The development of light harvesting systems based on heterostructures for
efficient conversion of solar energy to renewable energy is an emerging area of
research. Here, we have designed heterostructures by using carbon dots (C-dots)
and zinc oxide nanoparticles (ZnO NP) to develop an efficient light harvesting
system. Interestingly, the conduction band and the valence band positions of ZnO
NP are lower than the LUMO and HOMO positions of C-dots in this type II
heterostructure of C dot-ZnO NP, which causes efficient charge separation and
photocurrent generation. Steady state and time resolved spectroscopic studies
reveal that an efficient photoinduced electron transfer occurs from C dots to ZnO
NP and a simultaneous hole transfer occurs from the valence band of ZnO NP to the
HOMO of C dots. The calculated rate of electron transfer is found to be 3.7 * 109
s-1 and the rate of hole transfer is found to be 3.6 * 107 s-1. The enhancement
of photocurrent (11 fold) under solar light irradiation of the C dot-ZnO NP
heterostructure opens up new possibilities to design efficient light harvesting
systems.
PMID- 28489114
TI - Physical chemistry in a single live cell: confocal microscopy.
AB - A live cell is a complex, yet extremely important container. Understanding the
dynamics in a selected intracellular component is a challenging task. We have
recently made significant progress in this direction using a confocal microscope
as a tool. The smallest size of the focused spot in a confocal microscope is ~0.2
MUm (200 nm). This is nearly one hundred times smaller than the size of a live
cell. Thus, one can selectively study different intracellular
components/organelles in a live cell. In this paper, we discuss how one can image
different intracellular components/organelles, record fluorescence spectra and
decay at different locations, ascertain local polarity and viscosity, and monitor
the dynamics of solvation, proton transfer, red-ox and other phenomena at
specified locations/organelles inside a cell. We will highlight how this
knowledge enriched us in differentiating between cancer and non-cancer cells, 3D
tumor spheroids and towards drug delivery.
PMID- 28489116
TI - Investigation of the push-pull effects on beta-functionalized benzoporphyrins
bearing an ethynylphenyl bridge.
AB - A series of beta-pyrrole functionalized push-pull porphyrins with amine push
groups linked via an ethynylphenyl spacer, and cyclic imide or carboxylic esters
as pull groups have been newly synthesized and characterized. The beta-pyrrole
functionalized ethynylphenyl spacer extends the conjugation of the porphyrin pi
system, as reflected by their red-shifted absorbance and fluorescence spectra.
The computed structures revealed no steric hindrance between the porphyrin pi
system and the beta-substituents. The calculated HOMO and LUMO of compounds WJ2
and WJ3 display significant segregation, where the electron density in the HOMO
and LUMO is mainly located at the donor component and the acceptor component,
respectively. The orbital segregation is likely attributed to the introduction of
the electron-donating amine group at the porphyrin periphery. Electrochemical
studies revealed the expected lower HOMO-LUMO gap as a result of the facile
oxidation and reduction of the push-pull porphyrins. As a consequence of the push
pull effects, a reduction in fluorescence intensity and lifetime was observed,
especially for compound WJ3 having two electron-donating amino groups and a
strongly electron-withdrawing cyclic imide group. Femtosecond transient
absorption spectral studies revealed the successful formation of the singlet
excited state in all of these push-pull porphyrins. Due to the occurrence of
intramolecular charge transfer-type interactions, relaxation of the singlet
excited state was found to be faster in compound WJ3 compared to other two
derivatives in polar solvent but not in nonpolar solvent. Such charge transfer
type interactions from the triplet excited state were also observed in the case
of compound WJ3 in benzonitrile. The present findings bring out the importance of
push-pull effects in governing the ground and excited (singlet and triplet) state
properties of free-base porphyrins.
PMID- 28489117
TI - Survival of sealants in molars affected by molar-incisor hypomineralization: 18
month follow-up.
AB - The objective of this study was to evaluate the clinical survival of sealants
applied in first permanent molars (FPMs) affected by molar-incisor
hypomineralization (MIH), at 18 months of follow-up. Forty-one first permanent
molars were selected from 21 children, 6-8 years of age. MIH was classified by
one calibrated examiner (kappa = 0.80) according to EAPD criteria. The inclusion
criteria were fully erupted FPMs with MIH or sound FPMs (without MIH) for which
sealant treatment was indicated. The FPMs were assigned to two groups: CG
(control group) and HG (MIH group). Both groups were treated with sealant
(FluroShield). Clinical follow-up was performed from baseline to 18 months to
assess anatomical form, marginal adaptation, retention and presence of caries,
according to criteria set by the United States Public Health Service-Modified,
and was conducted by a blinded examiner (kappa = 0.80). The actuarial method was
used to evaluate the survival of the sealants. The survival rates for the groups
were compared using Fisher's exact test (alpha = 5%). The cumulative survival
rates were 81% at 1 month, 68.8% at 6 months, 68.8% at 12 months, and 62.6% at 18
months for CG, and 88% at 1 month, 84% at 6 months, 76% at 12 months, and 72% at
18 months for HG. No significant difference was found between the groups. The
sealants in molars affected by MIH presented a survival rate similar to the
sealants in the control, suggesting that sealants may be an adequate approach for
preventing carious lesions in MIH-affected molars.
PMID- 28489118
TI - Analysis of GLUT-1, GLUT-3, and angiogenic index in syndromic and non-syndromic
keratocystic odontogenic tumors.
AB - The aim of this study was to evaluate the immunoexpression of glucose
transporters 1 (GLUT-1) and 3 (GLUT-3) in keratocystic odontogenic tumors
associated with Gorlin syndrome (SKOTs) and non-syndromic keratocystic
odontogenic tumors (NSKOTs), and to establish correlations with the angiogenic
index. Seventeen primary NSKOTs, seven recurrent NSKOTs, and 17 SKOTs were
selected for the study. The percentage of immunopositive cells for GLUT-1 and
GLUT-3 in the epithelial component of the tumors was assessed. The angiogenic
index was determined by microvessel count. The results were analyzed
statistically using the nonparametric Kruskal-Wallis test and Spearman's
correlation test. High epithelial immunoexpression of GLUT-1 was observed in most
tumors (p = 0.360). There was a higher frequency of negative cases for GLUT-3 in
all groups. The few GLUT-3-positive tumors exhibited low expression of this
protein in epithelial cells. No significant difference in the angiogenic index
was observed between groups (p = 0.778). GLUT-1 expression did not correlate
significantly with the angiogenic index (p > 0.05). The results suggest that the
more aggressive biological behavior of SKOTs when compared to NSKOTs may not be
related to GLUT-1 or GLUT-3 expression. GLUT-1 may play an important role in
glucose uptake by epithelial cells of KOTs and this process is unlikely related
to the angiogenic index. GLUT-1 could be a potential target for future
development of therapeutic strategies for KOTs.
PMID- 28489119
TI - Cardiovascular disease in women: are we aware?
PMID- 28489120
TI - Overactive bladder: pharmacological treatment.
PMID- 28489121
TI - Diethylpropion and mazindol: An end to the discussion?
AB - Antiobesity pharmacotherapy remains the main point of disagreement among both
scientists and regulators. This is probably due to small sample sizes, high
levels of heterogeneity, and low methodological quality. For many years, Brazil
was one of the largest consumers of appetite suppressants worldwide, with
evidence of irrational use of this drug class. Therefore, the country was the
scene of a debate that divided the Brazilian Health Surveillance Agency (Anvisa -
Agencia Nacional de Vigilancia Sanitaria) and medical societies over the
maintenance record of diethylpropion, mazindol and fenproporex. In this context,
this commentary presents new arguments to contribute to the discussion, as well
as recommendations for future studies.
PMID- 28489122
TI - Minimally invasive endoscopic treatment of necrotizing pancreatitis: A case
report with images and review of the literature.
AB - Necrotizing pancreatitis with fluid collections can occur as a complication of
acute pancreatitis. The management of these patients depends on the severity and
involves multiple medical treatment modalities, as clinical intensive care and
surgical intervention. In this article, we show a severe case of walled-off
pancreatic necrosis that was conducted by endoscopic drainage with great clinical
outcome.
PMID- 28489123
TI - Acute amiodarone toxicity causing respiratory failure.
AB - A 66-year-old male patient was referred to our clinic with severe pneumonia.
Bronchoscopy was performed due to clinical worsening despite antibiotics and
diuretic therapy, respiratory failure and radiographic progression. Because
bacterial cultures of the bronchoalveolar lavage fluid were negative and after
using amiodarone for almost one month, we eliminated amiodarone from his
medication regimen due to suspicion of amiodarone toxicity. Accordingly, we also
initiated systemic steroid therapy. Chest X-ray done after 72 hours showed a
significant resolution of lung consolidations and the patient exhibited
significant clinical improvement, with decline of his oxygen requirements.
PMID- 28489124
TI - Retroauricular pain caused by Eagle syndrome: A rare presentation due to
compression by styloid process elongation.
AB - Eagle syndrome is a rare condition presenting with retroauricular pain (usually
as main symptom) associated with dysphagia, headache, neck pain on rotation and,
much rarelier, stroke. This occurs due to styloid process elongation. Sometimes,
there is also styloid ligament calcification, which can cause compression of
nerves and arteries and the symptoms above. Treatment can be conservative with
pain modulators (e.g. pregabalin) or infiltrations (steroids or anesthetics
drugs). In refractory cases, surgical approach aiming to reduce the size of the
styloid process can be performed. We present a rare case of Eagle syndrome
(documented by computed tomography) with good response to clinical treatment.
PMID- 28489125
TI - Severe hypoproteinemia as a harbinger of Menetrier's disease in autoimmune
pancreatitis.
AB - Menetrier's disease is an extremely rare disease of unknown etiology causing
gastric mucosal hypertrophy and protein-losing gastropathy. Rare cases of this
condition have been reported in patients with autoimmune diseases. However, to
the best of our knowledge, Menetrier's disease associated with autoimmune
pancreatitis (AIP) has never been reported. We described a case of severe
hypoproteinemia as a harbinger of Menetrier's disease associated with AIP. The
patient was successfully treated with octreotide and high-protein diet, which led
to symptomatic remission and significant improvement in serum levels of albumin
and recovery of the nutritional status. Thus, in AIP patients presenting with
severe and persistent hypoproteinemia without apparent cause, clinicians need to
consider Menetrier's disease in the differential diagnosis. In this setting,
endoscopic evaluation with histological examination of gastric biopsy material,
including a full-thickness mucosal biopsy of involved mucosa, may be helpful in
promptly establishing the diagnosis and allowing appropriate and timely therapy.
PMID- 28489126
TI - Solid pseudopapillary tumor of the pancreas: Clinical features, diagnosis and
treatment.
AB - Introduction:: Solid pseudopapillary tumor of the pancreas (SPTP) is a rare
neoplasm of low malignant potential with uncertain behavior, diagnosed mainly in
young women. Method:: Our report comprises a series of cases of SPTP reviewed
retrospectively, highlighting clinical, tomographic and immunohistochemical
features, treatment performed and outcomes. Results:: Thirteen patients were
found to have pancreatic [solid] masses on computed tomography scan measuring a
mean diameter of 8.8 cm. All patients underwent complete surgical excision.
Immunohistochemistry confirmed diagnosis in all cases. Conclusion:: SPTP occurs
more frequently in young women. Diagnostic suspicion lies on the finding of a
bulky, solid and cystic pancreatic mass. Imaging findings might provide
diagnostic information before resection. Conservative approaches can be used in
selected cases and survival rates are usually excellent following complete
resection.
PMID- 28489127
TI - Genotype 1 of human parvovirus B19 in clinical cases.
AB - Introduction:: Virus surveillance strategies and genetic characterization of
human parvovirus B19 (B19V) are important tools for regional and global control
of viral outbreak. In Sao Paulo, Brazil, we performed a study of B19V by
monitoring the spread of this virus, which is an infectious agent and could be
mistakenly reported as a rash and other types of infection. Method:: Serum
samples were subjected to enzyme immunoassay, real time polymerase chain
reaction, and sequencing. Results:: From the 462 patients with suspected cases of
exanthematic infections, the results of the 164 serum samples were positive for
B19V immunoglobulin M. Among these cases, there were 38 patients with erythema
infections and B19-associated with other infections such as encephalitis, hydrops
fetalis, chronic anemia, hematological malignancies. These samples were sequenced
and identified as genotype 1. Conclusion:: This study showed patients with
infections caused by B19V and sequencing genotype 1. Continuous monitoring is
necessary to detect all known genotypes, and the emergence of new genotypes of
these viruses for case management in public health control activities.
PMID- 28489128
TI - Obesity, bariatric surgery and oxidative stress.
AB - Introduction:: Obesity refers to the accumulation of fatty tissues and it favors
the occurrence of oxidative stress. Alternatives that can contribute to body
weight reduction have been investigated in order to reduce the production of
reactive oxygen species responsible for tissue damage. The aim of the current
study was to assess whether the oxidant and antioxidant markers of obese women
before and after bariatric surgery were able to reduce oxidative damage. Method::
We have assessed 16 morbidly obese women five days before and 180 days after the
surgery. The control group comprised 16 non-obese women. Levels of thiobarbituric
acid-reactive substances, carbonylated proteins, reduced glutathione and ascorbic
acid were assessed in the patients' plasma. Results:: Levels of lipid
peroxidation and protein carbonylation in the pre-surgical obese women were
higher than those of the controls and post-surgical obese women. Levels of
reduced glutathione in the pre-surgical obese women were high compared to the
controls, and declined after surgery. Levels of ascorbic acid fell in the pre-
surgical obese women compared to the control and post-surgical obese women.
Conclusion:: Body weight influences the production of reactive oxygen species.
Bariatric surgery, combined with weight loss and vitamin supplementation, reduces
cellular oxidation, thus reducing tissue damage.
PMID- 28489129
TI - Growth velocity and weight gain in prepubertal asthmatic children.
AB - Objective: : To evaluate the stature growth rate (GR) and the weight gain of
prepubertal asthmatic children. Method:: A retrospective cohort study evaluating
medical records of 85 children diagnosed with asthma, aged less than 9 years, of
both sexes, with at least one year of follow-up in the allergy outpatient clinic.
The data on the disease, weights and heights were collected through a
standardized questionnaire on two occasions, with an interval of one year. The
curves proposed by Tanner were applied for the analysis of the GR, and the Z
score of the GR (ZGR) was calculated. Results:: Excess weight (risk for
overweight, overweight and obesity) was observed in 31.8% (27/85) of the
patients, but there was no association with the severity of asthma. Low GR (ZGR <
-2) was found in 13.9% (11/79) of patients, most frequently among children with
moderate/severe persistent asthma compared to persistent mild and intermittent
forms (7/11 - 63.6% vs. 21/68 - 30.2%, respectively, p=0.047). Use of steroids
(dose, type and time of use) was not associated with GR. Conclusion:: GR was most
affected in children with moderate/severe asthma.
PMID- 28489130
TI - Impact of coronary intensive care unit in treatment of myocardial infarction.
AB - Introduction: : The mortality rate attributed to ST-segment elevation myocardial
infarction (STEMI) has decreased in the world. However, this disease is still
responsible for high costs for health systems. Several factors could decrease
mortality in these patients, including implementation of cardiac intensive care
units (CICU). The aim of this study was to evaluate the effect of CICU
implementation on prescribed recommended treatments and mortality 30 days after
STEMI. Method:: We performed a retrospective study with patients admitted to CICU
between 2005 and 2006 (after group) and between 2000 and 2002, before CICU
implementation (before group). Results:: The after group had 101 patients, while
the before group had 143 patients. There were no differences in general
characteristics between groups. We observed an increase in angiotensin-converting
enzyme inhibitors, clopidogrel and statin prescriptions after CICU
implementation. We did not find differences regarding number of patients
submitted to reperfusion therapy; however, there was an increase in primary
percutaneous angioplasty compared with thrombolytic therapy in the after group.
There was no difference in 30-day mortality (before: 10.5%; after: 8.9%;
p=0.850), but prescription of recommended treatments was high in both groups.
Prescription of angiotensin-converting enzyme inhibitors and beta-blocker
decreased mortality risk by 4.4 and 4.9 times, respectively. Conclusion:: CICU
implementation did not reduce mortality after 30 days in patients with STEMI;
however, it increased the prescription of standard treatment for these patients.
PMID- 28489131
TI - Incidence of delirium in postoperative patients treated with total knee and hip
arthroplasty.
AB - Introduction:: Delirium is a common disorder that can potentiate mortality and
comorbidity rates of patients hospitalized in intensive care units. Patients
undergoing major orthopedic surgeries, such as knee and hip arthroplasty, are
particularly vulnerable as they often have multiple risk factors for this
disorder. Method: : Descriptive study of the incidence of delirium in patients
treated with total knee and hip arthroplasty, given the advanced age and
comorbidities in this population. We evaluated the medical records of patients
who had previously undergone the designated surgeries for identification of
postoperative delirium. Results:: We observed in this study an incidence of 8.92%
of delirium, mostly affecting females with a mean age of 73 years and
hypertension. Conclusion:: The incidence of delirium in our study is similar to
that observed in the general population, according to the literature. We found no
correlation with sleep disorders, smoking or diabetes mellitus in this study,
even though the importance of these factors for the onset of delirium is well
established in the literature.
PMID- 28489132
TI - Patient adherence to ischemic heart disease treatment.
AB - Introduction:: The effectiveness of the treatment of chronic diseases depends on
the participation of the patient, influenced by different sociocultural factors,
which are not fully recognized by the treatment routine. Objective:: To search
for some of these factors that hinder or facilitate adherence to treatment and
use of healthcare resources, approaching patients with ischemic heart disease.
Method:: A cross-sectional study was conducted using face-to-face interviews. We
applied semi-structured questionnaires to 347 individuals and recorded 141
interviews for qualitative analysis. Descriptors were selected to identify eight
categories of analyses. The quantitative data were submitted to descriptive
analysis of frequency. Results:: Only 2% had good medication adherence according
to score on Morisky questionnaire. About 23% bought statins; the others obtained
statin in the public health institution. Thirty-six speeches were selected and
classified according to the following categories: knowledge about disease and
medication, difficulty of acquisition, self management of treatment, difficulties
of access to health services, side effect of statins, caregiver support,
transportation to health services and concerns about the disease progression.
However, it was noticed that about 1/3 of the care outside the research
institution can be characterized as an attempt to bring rationalization to the
health system. Conclusion:: The improved adherence to chronic treatment of
ischemic heart disease depends on the establishment of effective flows for
referral and counter-referral from one care unit to another, relevant information
and clarification of the questions for the patients and the attention of health
professionals to the many social and cultural factors involved in treatment
adherence. New research should be focused on educational groups by integrated
multidisciplinary teams in order to share treatment decisions, thereby increasing
the patient's commitment to his own health.
PMID- 28489133
TI - Association between antipsychotics and cardiovascular adverse events: A
systematic review.
AB - Objective: : Determine whether there is an association between the risk of
cardiovascular adverse events and the use of antipsychotic agents. Method::
Analysis of original articles retrieved from the following databases: LILACS,
PubMed, Cochrane Controlled Trials Clinical Data Bank (CENTRAL) and PsycINFO,
without language restriction, dated until November 2015. After screening of 2,812
studies, three cohort original articles were selected for quality analysis.
Results:: 403,083 patients with schizophrenia and 119,015 participants in the
control group data were analyzed. The occurrence of cardiovascular events
observed in the articles was: 63.5% (article 1), 13.1% (article 2) and 24.95%
(article 3) in the group of treated schizophrenic patients, and 46.2%, 86.9% and
24.9%, respectively, in the control groups. Conclusion:: Clinical heterogeneity
among the studies led to a provisional response and made it impossible to perform
the meta-analysis, although the articles demonstrate an association between
cardiovascular adverse events and the use of antipsychotics. More quality
clinical trials are needed to support this evidence.
PMID- 28489134
TI - Dialectics of a medical provision policy in priority areas in Brazil.
AB - Introduction:: The people living in vulnerable areas that are difficult to access
in Brazil represent a portion of the population that has proven very sensitive to
lack of medical and health services. The government, seeking to solve the
situation urgently, implemented the More Doctors Program [Programa Mais Medicos,
in the Portuguese original] in 2013. Objective: : To discuss the More Doctors
Program, with the purpose of contributing to the debate on the provision of
medical policies in Brazil. Method:: Study based on the review of official
documents: Programa Mais Medicos - dois anos: mais saude para os brasileiros,
2015 [More Doctors Program - two years: more health for Brazilians, 2015];
Operational Audit Report, TC No 005391/2014-8, the Court of Auditors of Brazil;
and Medical Demography in Brazil 2015. Results:: The import of exchange
physicians without diploma revalidation has cast a shadow on the technical
quality of services offered to the population. In terms of infrastructure, the
reduction of resources paralyzed works and made the care network maintenance
projects impossible. The creation of new medical schools has created uncertainty
about the possibility of quality education being offered, with minimum and
sufficient structure including laboratories, clinics and teaching hospitals
indispensable to medical training. Conclusion:: The regional inequalities of
concentration and dispersion of physicians, showed by studies on medical
demography in Brazil, stem from several factors, including the lack of a career
path and working conditions. There is no point in having physicians if they do
not have safe and ethical conditions to establish the diagnosis and a treatment
plan, as well as to monitor the rehabilitation of the patient.
PMID- 28489135
TI - Accuracy of ultrasound to detect thrombosis in pregnancy: A systematic review.
AB - Objective: : To determine the diagnostic accuracy of ultrasound to detect deep-
vein thrombosis in pregnant patients. Method:: We searched Pubmed, LILACS,
Scopus, Google Scholar and System for Information on Grey Literature from
inception to April 2016. The reference lists of the included studies were
analyzed. Original articles from accuracy studies that analyzed ultrasonography
to diagnose deep-vein thrombosis in pregnant women were included. Reference
standard was the follow-up time. The QUADAS-2 score was used for quality
assessment. Results:: Titles and summaries from 2,129 articles were identified.
Four studies that evaluated deep-vein thrombosis in pregnant women were included.
In all, 486 participants were enrolled. High risk of bias was seen in three out
of four studies included regarding flow and timing domain of QUADAS-2. Negative
predictive value was 99.39%. Conclusion:: Accuracy of ultrasonography to diagnose
deep-vein thrombosis in pregnant women was not determined due to the absence of
data yielding positive results. Further studies of low risk of bias are needed to
determine the diagnostic accuracy of ultrasonography in this clinical scenario.
PMID- 28489136
TI - Hyperferritinemia in patients with nonalcoholic fatty liver disease.
AB - Objective: : In liver diseases, hyperferritinemia (HYF) is related to injured
cells in acquired and genetic conditions with or without iron overload. It is
frequent in patients with nonalcoholic fatty liver disease (NAFLD), in which it
is necessary to define the mean of HYF to establish the better approach for them.
The present study evaluated the significance of elevated ferritin in patients
with NAFLD and steatohepatitis (NASH). Method:: The review was performed using
search instruments of indexed scientific material, including MEDLINE (by PubMed),
Web of Science, IBECS and LILACS, to identify articles published in Portuguese,
English and Spanish, from 2005 to May, 2016. Studies eligible included place and
year of publication, diagnose criteria to NAFLD, specifications of serum ferritin
measurements and/or liver histopathologic study. Exclusion criteria included
studies with patients with alcohol consumption >= 20 g/day and other liver
diseases. Results:: A total of 11 from 30 articles were selected. It included
3,564 patients and they were cross-sectional, retrospective, case series and case
control. The result's analyses showed in 10 of these studies a relationship
between ferritin elevated serum levels and NAFLD/NASH with and without fibrosis
and insulin resistance. Conclusion:: Hyperferritinemia in patients with
NAFLD/NASH is associated more frequently with hepatocellular injury than
hemochromatosis. These data suggest the relevance to evaluate carefully HYF in
patients with NAFLD/NASH to establish appropriate clinical approach.
PMID- 28489137
TI - New light on executive function and attention deficit hyperactivity disorder.
PMID- 28489138
TI - Attention-deficit/hyperactivity disorder: the impact of methylphenidate on
working memory, inhibition capacity and mental flexibility.
AB - Objective: To compare children with attention-deficit/hyperactivity disorder
(ADHD), before and after the use of methylphenidate, and a control group, using
tests of working memory, inhibition capacity and mental flexibility. Methods:
Neuropsychological tests were administrated to 53 boys, 9-12 years old: the WISC
III digit span backward, and arithmetic; Stroop Color; and Trail Making Tests.
The case group included 23 boys with ADHD, who were combined type, treatment
naive, and with normal intelligence without comorbidities. The control group (n =
30) were age and gender matched. After three months on methylphenidate, the ADHD
children were retested. The control group was also retested after three months.
Results: Before treatment, ADHD children had lower scores than the control group
on the tests (p <= 0.001) and after methylphenidate had fewer test errors than
before (p <= 0.001). Conclusion: Methylphenidate treatment improves the working
memory, inhibitory control and mental flexibility of ADHD boys.
PMID- 28489139
TI - High expression of anti-apoptotic genes in grade I and II meningiomas.
AB - Objective: To evaluate the expression of c-FLIP, XIAP, Bcl-2, caspase 3, 8 and 9,
cytochrome c, APAF 1 and Smac/DIABLO genes related to apoptosis pathways.
Methods: The gene expression was evaluated in 30 meningiomas (WHO grades I and
II) and in 10 normal samples (from arachnoid tissue) through PCR-RT. Results: The
results showed higher expression of anti-apoptotic genes in meningiomas when
compared to the control group, which had a low expression of pro-apoptotic genes.
Conclusion: There is a possible block in the activation of caspases through the
intrinsic apoptosis pathway in meningiomas. c-FLIP modulates caspase 8 and, by
inhibiting its activation due to the lack of connection with the receiver, there
is a block to the FAS activation of apoptosis by its extrinsic pathway.
PMID- 28489140
TI - Different outcomes of phonemic verbal fluency in Parkinson's disease patients
with subthalamic nucleus deep brain stimulation.
AB - Subthalamic nucleus deep brain stimulation (STN-DBS) is a surgical technique to
treat motor symptoms in patients with Parkinson's disease (PD). Studies have
shown that STN-DBS may cause a decline in verbal fluency performance. We aimed to
verify the effects of STN-DBS on the performance of phonemic verbal fluency in
Brazilian PD patients. Sixteen participants were evaluated on the Unified
Parkinson's Disease Rating Scale - Part III and for phonemic fluency ("FAS"
version) in the conditions of on- and off-stimulation. We identified two
different patterns of phonemic verbal fluency outcomes. The results indicate that
there may be no expected pattern of effect of bilateral STN-DBS in the phonemic
fluency, and patients may present with different outcomes for some reason not
well understood.
PMID- 28489141
TI - Home-based exercise program in TSP/HAM individuals: a feasibility and
effectiveness study.
AB - Objective: To investigate the feasibility and effectiveness of a home-based
exercise program in TSP/HAM individuals. Methods: Twenty-three TSP/HAM
individuals divided in two groups according to Timed Up and Go (TUG) score (<20s
vs >=20s) performed a 20-week home-based exercise program. The primary outcomes
were exercise adherence, maximum voluntary isometric contraction of lower limbs
(MVIC), Barthel Index and SF-36. Secondary outcomes were adverse effects and
barriers to exercise practice. Results: MVIC and the social functioning domain in
SF-36 improved significantly in TUG <20s group. The individuals in the TUG >=20s
group improved significantly their physical functioning domain in SF-36. The
total adherence to the 20-week home-based exercise program was 90%. There were
mild to moderate adverse events related to exercise program. There were no
adverse events related to MVIC test. Conclusions: The home-based exercise program
was feasible and effective in improving disability and quality of life in
individuals with TSP/HAM.
PMID- 28489142
TI - Cognitive cooperation groups mediated by computers and internet present
significant improvement of cognitive status in older adults with memory
complaints: a controlled prospective study.
AB - Objective: To estimate the effect of participating in cognitive cooperation
groups, mediated by computers and the internet, on the Mini-Mental State
Examination (MMSE) percent variation of outpatients with memory complaints
attending two memory clinics. Methods: A prospective controlled intervention
study carried out from 2006 to 2013 with 293 elders. The intervention group (n =
160) attended a cognitive cooperation group (20 sessions of 1.5 hours each). The
control group (n = 133) received routine medical care. Outcome was the percent
variation in the MMSE. Control variables included gender, age, marital status,
schooling, hypertension, diabetes, dyslipidaemia, hypothyroidism, depression,
vascular diseases, polymedication, use of benzodiazepines, exposure to tobacco,
sedentary lifestyle, obesity and functional capacity. The final model was
obtained by multivariate linear regression. Results: The intervention group
obtained an independent positive variation of 24.39% (CI 95% = 14.86/33.91) in
the MMSE compared to the control group. Conclusion: The results suggested that
cognitive cooperation groups, mediated by computers and the internet, are
associated with cognitive status improvement of older adults in memory clinics.
PMID- 28489143
TI - The use of a formula-based ketogenic diet in children with refractory epilepsy.
AB - The ketogenic diet (KD) is a nonpharmacologic treatment that has been used for
refractory epilepsy since 1921. The KD is a high-fat, low-carbohydrate, and
restricted protein diet, which is calculated and weighed for each individual
patient. Introducing and maintaining the diet for a long time remains a
challenge. In this study, we evaluated the acceptability, tolerance, and efficacy
of a formula-based KD in 10 children with refractory epilepsy. The ketogenic
formula tested herein caused only mild KD-related adverse events and adequate
adherence. Moreover, 60% of patients had more than 50% seizure frequency
reduction and 10% were seizure-free.
PMID- 28489144
TI - Modified simple decompression in the treatment of cubital tunnel syndrome:
avoiding ulnar nerve subluxation.
AB - Objective: In this study, we propose a modification to the simple decompression
technique that contains the ulnar nerve in the cubital fossa, thus preventing
subluxation during forearm flexion movements. Methods: Five consecutive patients
with leprosy-associated cubital tunnel syndrome underwent surgery with the
modified technique between July 2011 and October 2012. Results: The most common
symptoms were neuropathic pain and sensory changes (both 60%). On the McGowan
scale, three patients maintained their preoperative score and two patients
improved by two points, while on the Louisiana State University Health Sciences
Center scale, two patients maintained the same scores, two improved by two
points, and one improved by one point. Four patients were able to discontinue
corticosteroid use. The mean follow-up time was 25.6 months (range 2-48 months).
There were no recurrences or subluxations in the long-term. Conclusion: This
alternative technique resulted in excellent functional results, as well as
successful withdrawal from corticosteroids. Furthermore, it resulted in no ulnar
nerve subluxations.
PMID- 28489145
TI - Mismatch between diagnostic reports and special educational needs classification
in a public educational system.
AB - Objective: To assess the diagnostic status, the sociodemographic and health
profiles for students with special educational needs (SEN) in a public
educational system, and to map their use of educational/social services. Methods:
The sample comprised 1,202 SEN students from a total of 59,344 students. Results:
Only 792 students of the 1,202 had an established diagnosis. The most prevalent
SEN condition was intellectual disability. There was a low percentage (29.4%) of
use of specialized educational services or support. It was found that, for some
neurodevelopmental disorders, prevalence data suggest an under-reporting in the
school system. Conclusion: Results suggest that there is a mismatch between the
diagnostic reports and the SEN condition legally recognized according to
Brazilian law, in addition to the under-reporting and under specialized service
use of students with disabilities.
PMID- 28489146
TI - Acute muscular weakness in children.
AB - Acute muscle weakness in children is a pediatric emergency. During the diagnostic
approach, it is crucial to obtain a detailed case history, including: onset of
weakness, history of associated febrile states, ingestion of toxic
substances/toxins, immunizations, and family history. Neurological examination
must be meticulous as well. In this review, we describe the most common diseases
related to acute muscle weakness, grouped into the site of origin (from the upper
motor neuron to the motor unit). Early detection of hyperCKemia may lead to a
myositis diagnosis, and hypokalemia points to the diagnosis of periodic
paralysis. Ophthalmoparesis, ptosis and bulbar signs are suggestive of myasthenia
gravis or botulism. Distal weakness and hyporeflexia are clinical features of
Guillain-Barre syndrome, the most frequent cause of acute muscle weakness. If all
studies are normal, a psychogenic cause should be considered. Finding the
etiology of acute muscle weakness is essential to execute treatment in a timely
manner, improving the prognosis of affected children.
PMID- 28489147
TI - Professor Wadia's contributions to neurology and spinocerebellar ataxia type 2.
AB - The authors present a historical review of the seminal contributions of Professor
N. H. Wadia (1925-2016) to neurology, in particular, the first description of
spinocerebellar ataxia type 2.
PMID- 28489148
TI - Incidental detection of probable meningioma in brain scintigraphy using 99mTc
TRODAT-1.
PMID- 28489149
TI - Frontal lobes white matter abnormalities mimicking cystic leukodystrophy in
Wilson's disease.
PMID- 28489150
TI - Bing-Neel syndrome.
PMID- 28489151
TI - Erratum.
AB - [This corrects the article doi: 10.1590/0004-282X20160157] [This corrects the
article doi: 10.1590/0004-282x20160147] [This corrects the article doi:
10.1590/0004-282X20160052].
PMID- 28489152
TI - Evaluation of computer-generated guidelines for companions of paediatric patients
undergoing chemotherapy.
AB - Objective: To compare computer-generated guidelines with and without the use of a
Clinical Decision Support System - Oncology Care and Healthcare for Chemotherapy
Patients, for the caregivers of children undergoing chemotherapy. Methods: This
is a descriptive, evaluative, and quantitative study conducted at a paediatrics
hospital in Curitiba, Parana, Brazil, from December 2015 to January 2016. The
sample consisted of 58 participants divided into two groups: Group 1, without the
aid of software, and Group 2, with the aid of the software. The data were
analysed using the Mann-Whitney U test. Results: The guidelines revealed a
statistical significance (p<0.05), with a prevalence of a higher concordance
average in Group 2 in comparison with Group 1. Conclusion: Computer-generated
guidelines are a valuable qualitative support tool for nurses.
PMID- 28489153
TI - Changes in nursing practice to improve patient safety.
AB - Objective: To identify changes in nursing practice to improve the quality of care
and patient safety. Method: A case study conducted at an inpatient unit with
professionals from the patient safety centre and a nursing team, totalling 31
participants. Data were collected from May to December 2015 through interviews,
observations recorded in a field journal, and documentary analysis, followed by
content analysis. Results: The changes observed in the nursing practice included
the identification of care and physical risks, especially the risk of falls and
pressure injury, with the use of personal forms and the Braden scale;
notification of adverse events; adoption of protocols; effective communication
with permanent education and multiprofessional meetings. Conclusions: Changes
were observed in the nursing practice, chiefly focused on risk management.
PMID- 28489154
TI - Serum positive thyroglobulin antibodies: an old problem with new questions.
PMID- 28489155
TI - Subclinical carotid vascular disease and risk factors for atherosclerosis in type
1 and type 2 diabetes.
PMID- 28489157
TI - RESPECT TO HISTORY: VON PRESSER SYNDROME.
PMID- 28489156
TI - Impact of free thyroxine levels and other clinical factors on bare metal stent
restenosis.
AB - Objective: Thyroid hormones have both direct and indirect effects on
thermogenesis such as modulating vascular smooth muscle cell proliferation.
However, the influence of more subtle changes in thyroid hormones on coronary
atherosclerosis remains a matter of speculation. Smooth muscle cells play a
crucial role in the pathogenesis of in-stent restenosis (ISR). However, the
relationship between free thyroxine (fT4) and ISR has not been studied. In the
present study, we aimed to assess the role of preprocedural serum fT4 level on
the development of ISR in patients undergoing coronary bare metal stent (BMS)
implantation. Materials and methods: We enrolled and analyzed clinical,
biochemical, and angiographic data from 705 consecutive patients without a
history of primary thyroid disease [mean age 60.3 +/- 9.3 years, 505 (72%) male];
all patients had undergone BMS implantation and further control coronary
angiography owing to stable or unstable angina pectoris. Patients were divided
into 3 tertiles based on preprocedural serum fT4 levels. Results: ISR was
observed in 53 (23%) patients in the lowest tertile, 82 (35%) patients in the
second tertile, and 107 (46%) patients in the highest fT4 tertile (p < 0.001).
Using multiple logistic regression analysis, five characteristics emerged as
independent predictors of ISR: diabetes mellitus, smoking, HDL-cholesterol, stent
length, and preprocedural serum fT4 level. In receiver operating characteristics
curve analysis, fT4 level > 1.23 mg/dL had 70% sensitivity and 73% specificity
(AUC: 0.75, p < 0.001) in predicting ISR. Conclusion: Higher preprocedural serum
fT4 is a powerful and independent predictor of BMS restenosis in patients with
stable and unstable angina pectoris.
PMID- 28489158
TI - PREVALENCE AND PREDICTORS OF CHANGES IN BOWEL HABITS AFTER LAPAROSCOPIC
CHOLECYSTECTOMY.
AB - Background:: The incidence of cholecystolithiasis is approximately 15% of the
population. It is believed that between 30-40% of cholecystectomy patients have
symptoms after surgery, being changes in bowel habits the most common among them.
Aim:: 1) Defining the prevalence, and 2) identifying predictors of changes in
bowel habits after laparoscopic cholecystectomy. Methods:: This is a
retrospective cross-sectional study with an initial sample of 150 patients
diagnosed with cholecystolithiasis operated between July and September 2014.
Patients were submitted to a questionnaire about the presence of gastrointestinal
symptoms and changes in stools consistency before and after the surgical
procedure. They were divided into two groups (with or without changes in bowel
habits) being combined with the following variables: high blood pressure, body
mass index, hypothyroidism, adherence to postoperative dietary orientations,
previous abdominal and bariatric surgery. Results:: The prevalence of changes in
bowel habits in the study population was 35.1%. The association between it and
gastrointestinal symptoms was demonstrated to be statistically significant
(0/002=7.981; p=0.005), and people who did not have gastrointestinal symptoms had
2.34 times the odds of not presenting changes in bowel habits. None of the other
investigated factors had shown to be a predictor of risk for post-cholecystectomy
changes in bowel habits. Conclusion:: 1) There was a high prevalence of changes
in bowel habits, and 2) there was association between changes in bowel habits and
the presence of gastrointestinal symptoms. Racional:: A incidencia da
colecistopatia calculosa e de aproximadamente 15% da populacao brasileira.
Acredita-se que entre 30-40% dos pacientes colecistectomizados apresentem
sintomas pos-operatorio, sendo a alteracao do habito intestinal o mais comum.
Objetivo:: 1) Determinar a prevalencia, e 2) identificar preditores de mudancas
do habito intestinal pos-colecistectomia videolaparoscopica. Metodos:: Estudo
transversal retrospectivo com amostra inicial de 150 pacientes diagnosticados com
colecistopatia calculosa, operados entre julho e setembro de 2014. Os pacientes
foram submetidos a um questionario sobre a presenca de sintomas gastrointestinais
apos a operacao, e a alteracoes do aspecto das fezes antes e depois do
procedimento. A amostra foi dividida em dois grupos (com ou sem mudancas do
habito intestinal) sendo realizadas associacoes com as seguintes variaveis:
hipertensao arterial, IMC, hipotireoidismo, seguimento de dieta no pos
operatorio, operacao abdominal previa e operacao bariatrica. Resultados:: A
prevalencia de mudancas do habito intestinal na populacao estudada foi de 35,1%.
A associacao entre elas e sintomas gastrointestinais demonstrou-se
estatisticamente significativa (0/002=7,981; p=0,005), sendo que as pessoas que
nao apresentavam os sintomas tinham 2,34 vezes mais chances de nao apresentarem
mudancas do habito intestinal. Nenhum dos demais fatores investigados demonstrou
ser preditor de risco para mudancas do habito intestinal pos-colecistectomia.
Conclusoes:: 1) Observou-se alta prevalencia de mudancas do habito intestinal, e
2) houve associacao entre mudanca do habito intestinal e a presenca de sintomas
gastrointestinais.
PMID- 28489160
TI - NUTRITIONAL ASPECTS AND THE USE OF NUTRITIONAL SUPPLEMENTS BY WOMEN WHO UNDERWENT
GASTRIC BYPASS.
AB - Background: Bariatric surgery is deemed one of the most effective procedures for
the treatment of obesity and it aims at the reduction and maintenance of weight
loss in long term, as the control of the related comorbidities. Aim: Quantify the
occurrence of alterations of the gastrointestinal tract, suggestive signs of
nutritional deficiencies and the use of supplements in a group of women
undergoing bariatric surgery. Methods: The sample consisted of women aged 20-65
years submitted to Roux-en-Y gastric bypass with monitoring equal to or higher
than 24 months. For the qualitative analysis, the Feeding Frequency Questionnaire
was used. Results: In the postoperative period, alopecia was the most reported
(79.3%), followed by changes in the texture of the nails, both considered
predictive of nutritional deficiencies. Changes in the gastrointestinal tract
were described in 86.2%, and episodes of dumping were reported in 65.5%.
Qualitative analysis has shown reduced daily consumption of sources of animal and
plant proteins. Conclusion: After bariatric surgery can occur flatulence,
vomiting and dumping syndrome as the most frequent representative symptoms of
digestive functional disorders. Alopecia and nail changes are the most important
signs of nutritional deficiency. The use of dietary supplements in the
postoperative period is scarce and sporadic.
PMID- 28489159
TI - CHANGING PARADIGMS IN PREOPERATIVE FASTING: RESULTS OF A JOINT EFFORT IN
PEDIATRIC SURGERY.
AB - Background:: Current researches associate long fasting periods to several adverse
consequences. The fasting abbreviation to 2 h to clear liquids associated with
the use of drinks containing carbohydrates attenuates endocrinometabolic response
to surgical trauma, but often is observed children advised to not intake food
from 00:00 h till the scheduled surgical time, regardless of what it is. Aim:: To
evaluate the safety of a protocol of preoperative fasting abbreviation with a
beverage containing carbohydrates, and early postoperative feeding in children
underwent elective small/mid-size surgical procedures during a national task
force on pediatric surgery. Methods:: Thirty-six patients were prospectively
included, and for several reasons five were excluded. All 31 who remained in the
study received a nutritional supplement containing 150 ml of water plus 12.5%
maltodextrin 2 h before the procedure. Data of the pre-operative fasting time,
anesthetic complications and time of postoperative refeeding, were collected.
Results:: Twenty-three (74.2%) were males, the median age was 5 y, and the median
weight was 20 kg. The median time of pre-operative fasting was 145 min and the
time of post-operative refeeding was 135 min. There were no adverse effects on
the anesthetic procedures or during surgery. Post-operatively, two children
(6.5%) vomited. Conclusion:: The abbreviation of pre-operative fasting to 2 h
with beverage containing carbohydrate in pediatric surgery is safe. Early
refeeding in elective small/mid-size procedures can be prescribed. Racional::
Trabalhos atuais associam longos periodos de jejum com diversas consequencias
adversas. A abreviacao do jejum de 2 h para liquidos claros associado ao uso de
bebidas contendo carboidratos atenua resposta endocrinometabolica ao trauma,
porem frequentemente as criancas sao orientadas a nao ingerir alimentos a partir
das 00:00 h do dia anterior a operacao, independente do horario do procedimento
cirurgico. Objetivo:: Avaliar a seguranca de um protocolo de abreviacao do jejum
pre-operatorio, com o uso de bebida contendo carboidratos, e realimentacao
precoce. Metodos:: Foram avaliados prospectivamente 36 criancas submetidas a
procedimentos cirurgicos eletivos de pequeno e medio porte. Cinco foram
posteriormente excluidos do estudo. Todos os 31 remanescentes receberam
suplemento nutricional com maltodextrina 12,5% em 150 ml de agua aproximadamente
2 h antes do procedimento. Foram coletados dados do tempo de jejum pre
operatorio, complicacoes anestesicas e tempo de realimentacao. Resultados:: Vinte
e tres (74,2%) eram do genero masculino, com idade mediana de cinco anos e peso
mediano de 20 kg. O tempo mediano de jejum pre-operatorio foi de 145 min e o
tempo mediano para realimentacao foi de 135 min. Nao houve eventos adversos
durante a anestesia ou operacao. No periodo pos-operatorio, duas (6,5%) criancas
vomitaram. Conclusao:: A abreviacao de jejum pre-operatorio para 2 h com uso de
bebida contendo carboidratos, em operacoes eletivas de criancas, e seguro e nao
esta associado ao maior risco de broncoaspiracao pulmonar. Realimentacao precoce
pode ser prescrita nos procedimentos cirurgicos analisados.
PMID- 28489161
TI - QUALITY OF LIFE AFTER VERTICAL GASTRECTOMY EVALUATED BY THE BAROS QUESTIONNAIRE.
AB - Background: The satisfactory outcome in the surgical treatment of obesity must
include, in addition to weight loss, a significant change in the pre-existing
comorbidities and in the quality of life. Aim: To evaluate the quality of life in
the late postoperative period in patients that underwent videolaparoscopic sleeve
gastrectomy. Methods: It was applied the questionnaire "Bariatric Analysis and
Reporting Outcome System" (BAROS) in patients that underwent videolaparoscopic
sleeve gastrectomy. Results: A total of 47 patients between 21-60 years old were
evaluated. The total mean of BMI before surgery was 43.06+/-5.87 kg/m2. The
average percentage of the reduction of excess weight after surgery was 85.46+/
23.6%. The score obtained by patients in the questionnaire about the improvement
in the quality of life showed excellent (36.17%), very good (40.43%), good
(21.28%) and reasonable (2.13%) results. There was clinical improvement after
surgery in all comorbidities investigated. Conclusion: The weight loss was
critical to improve the quality of life and offered the resolution or clinical
improvement in all of the investigated comorbidities in patients submitted to
sleeve gastrectomy.
PMID- 28489162
TI - ENDOSCOPIC SLEEVE GASTROPLASTY FOR OBESITY TREATMENT: TWO YEARS OF EXPERIENCE.
AB - Background: Bariatric endoscopic techniques are minimally invasive and induce
gastric volume reduction to treat obesity. Aim : To evaluate endoscopic sleeve
gastroplasty (Apollo method) using a suturing method directed at the greater
curvature, as well as the perioperative care, two year safety and weight loss.
Method: Prospective single-center study over 154 patients (108 females) using the
endoscopic sleeve gastroplasty procedure under general anesthesia with overnight
inpatient observation. Of the154 initial patients, 143 were available for 1-month
of follow-up, 133 for 6-month, 64 for 12-month and 28 completed the 24 month
assessment. Follow-up was carried out by a multidisciplinary team (nutritionist
and psychologist). Outcomes evaluated were: change in BMI; change in body weight
(TBWL); % of loss of initial body weight (%TBWL); % of excess body weight loss
(%EWL) (segregated in > or <25% and adverse effects. Voluntary oral contrasted
radiological examinations were scheduled to assess the gastroplasty at different
times post-procedure. Results: Mean age was 44.9 (23-69) years. At 24 months
after the procedure baseline mean BMI change from 38.3 to 30.8 kg/m2. TBWL, %TBWL
and %EWL were of 21.3 kg, 19.5% and 60.4% respectively. 85.7% of patients achieve
the goal of >25% %EWL. There were no mayor adverse events intraprocedure or
during the 24 months of follow-up . Conclusion: Endoscopic sleeve gastroplasty
with regular monitoring by a multidisciplinary team can be considered an
effective, safe and well tolerated procedure for obesity treatment, at least for
two years of follow-up.
PMID- 28489163
TI - HYPERVASCULAR LIVER LESIONS IN RADIOLOGICALLY NORMAL LIVER.
AB - Background: The hypervascular liver lesions represent a diagnostic challenge.
Aim: To identify risk factors for cancer in patients with non-hemangiomatous
hypervascular hepatic lesions in radiologically normal liver. Method: This
prospective study included patients with hypervascular liver lesions in
radiologically normal liver. The diagnosis was made by biopsy or was presumed on
the basis of radiologic stability in follow-up period of one year. Cirrhosis or
patients with typical imaging characteristics of haemangioma were excluded.
Results: Eighty-eight patients were included. The average age was 42.4. The
lesions were unique and were between 2-5 cm in size in most cases. Liver biopsy
was performed in approximately 1/3 of cases. The lesions were benign or most
likely benign in 81.8%, while cancer was diagnosed in 12.5% of cases. Univariate
analysis showed that age >45 years (p< 0.001), personal history of cancer
(p=0.020), presence of >3 nodules (p=0.003) and elevated alkaline phosphatase
(p=0.013) were significant risk factors for cancer. Conclusion: It is safe to
observe hypervascular liver lesions in normal liver in patients up to 45 years,
normal alanine aminotransaminase, up to three nodules and no personal history of
cancer. Lesion biopsies are safe in patients with atypical lesions and define the
treatment to be established for most of these patients.
PMID- 28489164
TI - DIFFERENT PROTOCOLS OF POSTCONDITIONING DOES NOT ATTENUATE MESENTERIC ISCHEMIA
REPERFUSION INJURY AFTER SHORT-TERM REPERFUSION.
AB - Background: Mesenteric ischemia is a challenging diagnosis. Delay in diagnosis
can lead to extent bowel necrosis and poor outcomes. Ischemia and reperfusion
syndrome plays an important role in this scenario. Aim: To access effects of
different post-conditioning cycles on mesenteric ischemia-reperfusion syndrome.
Method: Twenty-five rats were assigned into five groups: Sham, used to establish
normal parameters; control group, submitted to mesenteric ischemia for 30 min; in
groups GP3, GP1 and GP30, ischemia was followed by post-conditioning protocol,
which consisted of 1 cycle of 3 min (GP3), 3 cycles of 1 min (GP1) or 6 cycles of
30 s (GP30), respectively. Ileum samples were harvested after one hour of
reperfusion. Intestinal mucosal injury was evaluated through histopathological
analysis. Results: The average of mesenteric injury degree was 0 in the sham
group, 3.6 in the control group, 3.4 in GP3, 3.2 in GP1, and 3.0 in GP30; villous
length average was 161.59 in sham group, 136.27 in control group, 135.89 in GP3,
129.46 in GP1, and 135.18 in GP30. Was found significant difference between sham
and other groups (p<0.05); however, there was no difference among post
conditioning groups. Conclusion: Post-conditioning adopted protocols were not
able to protect intestinal mucosa integrity after mesenteric ischemia and short
term reperfusion.
PMID- 28489165
TI - DETECTION OF OCCULT LYMPH NODE TUMOR CELLS IN NODE-NEGATIVE GASTRIC CANCER
PATIENTS.
AB - Background: The presence of lymph nodes metastasis is one of the most important
prognostic indicators in gastric cancer. The micrometastases have been studied as
prognostic factor in gastric cancer, which are related to decrease overall
survival and increased risk of recurrence. However, their identification is
limited by conventional methodology, since they can be overlooked after routine
staining. Aim: To investigate the presence of occult tumor cells using
cytokeratin (CK) AE1/AE3 immunostaining in gastric cancer patients histologically
lymph node negative (pN0) by H&E. Methods: Forty patients (T1-T4N0) submitted to
a potentially curative gastrectomy with D2 lymphadenectomy were evaluated. The
results for metastases, micrometastases and isolated tumor cells were also
associated to clinicopathological characteristics and their impact on stage
grouping. Tumor deposits within lymph nodes were defined according to the tumor
node-metastases guidelines (7th TNM). Results: A total of 1439 lymph nodes were
obtained (~36 per patient). Tumor cells were detected by immunohistochemistry in
24 lymph nodes from 12 patients (30%). Neoplasic cells were detected as a single
or cluster tumor cells. Tumor (p=0.002), venous (p=0.016), lymphatic (p=0.006)
and perineural invasions (p=0.04), as well as peritumoral lymphocytic response
(p=0.012) were correlated to CK-positive immunostaining tumor cells in originally
negative lymph nodes by H&E. The histologic stage of two patients was upstaged
from stage IB to stage IIA. Four of the 28 CK-negative patients (14.3%) and three
among 12 CK-positive patients (25%) had disease recurrence (p=0.65). Conclusion:
The CK-immunostaining is an effective method for detecting occult tumor cells in
lymph nodes and may be recommended to precisely determine tumor stage. It may be
useful as supplement to H&E routine to provide better pathological staging.
PMID- 28489166
TI - ANATOMIC VARIATIONS OF HEPATIC ARTERY: A STUDY IN 479 LIVER TRANSPLANTATIONS.
AB - Background:: The incidence of anatomic variations of hepatic artery ranges from
20-50% in different series. Variations are especially important in the context of
liver orthotopic transplantation, since, besides being an ideal opportunity for
surgical anatomical study, their precise identification is crucial to the success
of the procedure. Aim:: To identify the anatomical variations in the hepatic
arterial system in hepatic transplantation. Methods:: 479 medical records of
transplanted adult patients in the 13-year period were retrospectively analyzed,
and collected data on hepatic arterial anatomy of the deceased donor. Results::
It was identified normal hepatic arterial anatomy in 416 donors (86.84%). The
other 63 patients (13.15%) showed some variation. According to the Michels
classification, the most frequently observed abnormalities were: right hepatic
artery branch of superior mesenteric artery (Type III, n=27, 5.63%); left hepatic
artery branch of the left gastric artery (Type II, n=13, 2.71%); right hepatic
artery arising from the superior mesenteric artery associated with the left
hepatic artery arising from the left gastric artery (Type IV, n=4, 0.83%).
Similarly, in relation to Hiatt classification, the most prevalent changes were:
right hepatic accessory artery or substitute of the superior mesenteric artery
(Type III, n=28, 6.05%)), followed by liver ancillary left artery or replacement
of gastric artery left (Type II, n=16, 3.34. Fourteen donors (2.92%) showed no
anatomical abnormalities defined in classifications, the highest frequency being
hepatomesenteric trunk identified in five (01.04%). Conclusion:: Detailed
knowledge of the variations of hepatic arterial anatomy is of utmost importance
to surgeons who perform approaches in this area, particularly in liver
transplantation, since their identification and proper management are critical to
the success of the procedure. Racional:: A incidencia das variacoes anatomicas da
arteria hepatica varia de 20-50% em diferentes casuisticas. Elas sao
especialmente importantes no contexto do transplante ortotopico hepatico, visto
que, alem de representar oportunidade ideal para seu estudo anatomico cirurgico,
a sua precisa identificacao e determinante para o sucesso do procedimento.
Objetivo:: Identificar as variacoes anatomicas no sistema arterial hepatico em
transplantes hepaticos. Metodo:: Foram analisados retrospectivamente, no periodo
de 13 anos, 479 prontuarios de pacientes adultos transplantados, sendo coletados
dados referentes a anatomia arterial hepatica do doador falecido. Resultados::
Identificou-se anatomia arterial hepatica normal em 416 doadores (86,84%). Os
outros 63 individuos (13,15%) apresentaram alguma variacao. De acordo com a
classificacao de Michels, as anomalias mais frequentes foram: arteria hepatica
direita ramo da arteria mesenterica superior (Tipo III, n=27, 5,63%); arteria
hepatica esquerda ramo da arteria gastrica esquerda (Tipo II, n=13, 2,71%);
arteria hepatica direita ramo da arteria mesenterica superior associada a arteria
hepatica esquerda ramo da arteria gastrica esquerda (Tipo IV, n=4, 0,83%). Do
mesmo modo, em relacao a Classificacao de Hiatt, as variacoes mais prevalentes
foram: arteria hepatica direita acessoria ou substituta da arteria mesenterica
superior (Tipo III, n=28, 6,05%), seguida da arteria hepatica esquerda acessoria
ou substituta da arteria gastrica esquerda (Tipo II, n=16, 3,34%). Quatorze
pessoas (2,92%) apresentaram alteracoes anatomicas sem classificacao definida,
sendo a de maior frequencia o tronco hepatomesenterico, identificado em cinco
(1,04%). Conclusao:: O conhecimento detalhado das variacoes da anatomia arterial
hepatica e de grande importancia aos cirurgioes que realizam abordagens nessa
regiao, em especial no transplante hepatico, visto que sua identificacao e
correto manejo sao fundamentais para o exito do procedimento.
PMID- 28489167
TI - PREOPERATIVE COMPUTED TOMOGRAPHY VOLUMETRY AND GRAFT WEIGHT ESTIMATION IN ADULT
LIVING DONOR LIVER TRANSPLANTATION.
AB - Background: Computed tomography volumetry (CTV) is a useful tool for predicting
graft weights (GW) for living donor liver transplantation (LDLT). Few studies
have examined the correlation between CTV and GW in normal liver parenchyma. Aim:
To analyze the correlation between CTV and GW in an adult LDLT population and
provide a systematic review of the existing mathematical models to calculate
partial liver graft weight. Methods: Between January 2009 and January 2013, 28
consecutive donors undergoing right hepatectomy for LDLT were retrospectively
reviewed. All grafts were perfused with HTK solution. Estimated graft volume was
estimated by CTV and these values were compared to the actual graft weight, which
was measured after liver harvesting and perfusion. Results: Median actual GW was
782.5 g, averaged 791.43+/-136 g and ranged from 520-1185 g. Median estimated
graft volume was 927.5 ml, averaged 944.86+/-200.74 ml and ranged from 600-1477
ml. Linear regression of estimated graft volume and actual GW was significantly
linear (GW=0.82 estimated graft volume, r2=0.98, slope=0.47, standard deviation
of 0.024 and p<0.0001). Spearman Linear correlation was 0.65 with 95% CI of 0.45
0.99 (p<0.0001). Conclusion: The one-to-one rule did not applied in patients
with normal liver parenchyma. A better estimation of graft weight could be
reached by multiplying estimated graft volume by 0.82.
PMID- 28489169
TI - MORTALITY OF URGENCY VERSUS ELECTIVE VIDEOLAPAROSCOPIC CHOLECYSTECTOMY FOR ACUTE
CHOLECYSTITIS.
AB - Background: Surgical approach is still controversial in patients with acute
cholecystitis: to treat clinically the inflammatory process and operate
electively later or to operate immediately on an emergency basis? Aim: To test
the hypothesis that urgent laparoscopic cholecystectomy in acute cholecystitis
has a higher mortality than elective laparoscopic cholecystectomy. Methods: From
the data available in Datasus, mortality was compared between patients undergoing
elective laparoscopic cholecystectomy for cholelithiasis and in urgency.
Calculations were made of the relative reduction in risk of death, absolute
reduction of risk of death and number needed to treat. Results: From 2009 to 2014
in Brazil, there were 250.439 laparoscopic cholecystectomy and 74.6% were
electives. Mortality in the emergency group was 4.8 times higher compared to the
elective group (0.0023% vs. 0.00048%). Despite the relative reduction in risk of
death (RRR) was 83%, in the calculation of absolute risk was found 0.0018 and
number needed to treat of 55,555. Conclusions: Despite the relative risk
reduction for mortality was high comparing elective vs. urgent basis, the
absolute risk reduction was minimal, since this outcome is very low in both
groups, suggesting that mortality should not have much influence on surgical
decision.
PMID- 28489168
TI - Angiolymphatic invasion as a prognostic fator in resected N0 pancreatic
adenocarcinoma.
AB - Background: Pancreatic adenocarcinoma remains one of the worst digestive cancers.
Surgical resection is the main target when treating a patient with curative
intent. Aim: To assess angiolymphatic invasion as a prognostic factor in resected
pN0 pancreatic cancer. Methods: Thirty-eight patients were submitted to
pancreatoduodenectomy due to head pancreatic cancer. Tumor size, margins, lymph
nodes, pTNM staging, angiolymphatic and perineural invasion were described in the
pathologists' reports. Results: Most patients were female. Overall median
survival was 13 months. Gemcitabine was the regimen of choice for chemotherapy in
selected patients; however, it did not improve overall survival. pR0 resection
had better survival compared with pR1. Within the pN0 group, survival was
significantly better in patients without angiolymphatic invasion. Conclusion:
Angiolymphatic invasion in N0 pancreatoduodenectomy can be demonstrated by the
Hematoxylin-Eosin stain and may predict a poor prognosis factor for those
patients.
PMID- 28489170
TI - MODIFIED ALVARADO SCORE IN CHILDREN WITH DIAGNOSIS OF APPENDICITIS.
AB - Background: Appendicitis is one of the most common abdominal emergency. Some
predictive scoring systems are recommended to decrease the rate of negative
appendectomy. Aim: To evaluate sensitivity, specificity, positive predictive
value, and negative predictive value of modified Alvarado score in children who
underwent appendectomy. Methods: Four hundred children with initial diagnosis of
appendicitis were randomly selected from patients who underwent appendectomy.
Modified Alvarado score was used for evaluation of the appendicitis, that was
confirmed using histology. Results: Of modified Alvarado score components,
anorexia; nausea and vomiting and rebound tenderness were significantly more
common in children with positive appendectomy in contrast to patients with
negative appendectomy. Sensitivity, specificity, positive predictive value, and
negative predictive value for modified Alvarado score were: 91.3%; 38.4%; 87.7%;
and 51.2% respectively. Conclusion: Alvarado score has high sensitivity but low
specificity for diagnosis of acute appendicitis in children.
PMID- 28489171
TI - ALTERNATIVE TECHNIQUE FOR CHOLECYSTECTOMY COMPARABLE TO SINGLE PORT.
AB - Background: With the advancement of laparoscopic surgery, new techniques have
been proposed and disseminated in order to reduce the surgical aggression and get
better cosmetic results. Aim: To present alternative technique for
videocholecystectomy comparable to single port technique using conventional
material for laparoscopic surgery. Method: Introduction of laparoscopic devices
using two incisions; gallbladder traction with thread, exposition of Calot
triangle, and ligature of cystic pedicle with polymer clips. Results: Nine
operations were carried out with this method, without complications and no
increase in operative time, being compared to conventional videocholecistectomy,
however vastly superior in aesthetic results. Conclusion: The technique is
feasible, reproducible, showing benefits to patient's safety.
PMID- 28489172
TI - LAPAROSCOPIC REPAIR OF LUMBAR HERNIA (GRYNFELT): TECHNICAL DESCRIPTION.
AB - Background:: Lumbar hernias are rare. Usually manifest with reducible volume
increase in the post-lateral region of the abdomen and may occur in two specific
anatomic defects: the triangles of Grynfelt (upper) and Petit (lower). Despite
controversies with better repair, laparoscopic approach, following the same
principle of the treatment of inguinal hernias, seems to present significant
advantages compared to conventional/open surgeries. However, some technical and
anatomical details of the region, non usual to general surgeons, are fundamental
for proper repair. Aim:: To present systematization of laparoscopic
transabdominal technique for repair of lumbar hernias with emphasis on anatomical
details. Method: : Patient is placed in the lateral decubitus. Laparoscopic
access to abdominal cavity is performed by open technique on the left flank, 1.5
cm incision, followed by introduction of 11 mm trocar for a 30o scope. Two other
5 mm trocars, in the left anterior axillary line, are inserted into the abdominal
cavity. The peritoneum of the left paracolic gutter is incised from the 10th rib
to the iliac crest. Peritoneum and retroperitoneal is dissected. Reduction of all
hernia contents is performed to demonstrate the hernia and its size. A 10x10 cm
polypropylene mesh is introduced into the retroperitoneal space and fixed with
absorbable staples covering the defect with at least 3-4 cm overlap.
Subsequently, is carried out the closure of the peritoneum of paracolic gutter.
Results:: This technique was used in one patient with painful increased volume in
the left lower back and bulging on the left lumbar region. CT scan was performed
and revealed left superior lumbar hernia. Operative time was 45 min and there
were no complications and hospitalization time of 24 h. Conclusion:: As in
inguinal hernia repair, laparoscopic approach is safe and effective for the
repair of lumbar hernias, especially if the anatomical details are adequately
respected. Racional:: As hernias lombares sao raras. Geralmente se manifestam com
aumento de volume redutivel na regiao postero-lateral do abdome e podem ocorrer
em dois defeitos anatomicos especificos: os triangulos de Grynfelt (superior) e
Petit (inferior). Apesar de controversias com relacao a melhor forma de reparo, a
abordagem laparoscopica, seguindo o mesmo principio do tratamento das hernias
inguinais, parece apresentar vantagens significativas em relacao as operacoes
convencionais/abertas. Entretanto, alguns detalhes tecnicos e anatomicos desta
regiao, nao usual aos cirurgioes gerais, sao fundamentais para o adequado reparo.
Objetivo:: Apresentar sistematizacao da tecnica laparoscopica transabdominal para
a correcao das hernias lombares com enfase nos detalhes anatomicos. Metodo::
Paciente e colocado em decubito lateral. O acesso laparoscopico a cavidade
abdominal e realizado pela tecnica aberta no flanco esquerdo, incisao de 1,5 cm,
seguida pela introducao de trocarteres de 11 mm para otica de 30o. Dois outros
trocarteres de 5 mm, na linha axilar anterior esquerda, sao inseridos na cavidade
abdominal. O peritonio da goteira paracolica esquerda e incisado desde a 10a
costela ate a crista iliaca. O peritonio e o retroperitoneal sao dissecados. A
reducao de todo o conteudo de hernia e realizada para demonstrar a hernia e seu
tamanho. Tela de polipropileno de 10x10 cm e introduzida no espaco
retroperitoneal e fixada com grampos absorviveis cobrindo o defeito com pelo
menos 3-4 cm de sobreposicao. Posteriormente, realiza-se o fechamento do
peritonio da goteira paracolica. Resultados:: Esta tecnica foi utilizada em um
paciente com aumento doloroso de volume na regiao lombar esquerda e abaulamento
na regiao lombar esquerda. Tomografia computadorizada foi realizada e revelou
hernia lombar superior esquerda. O tempo operatorio foi de 45 min e nao houve
complicacoes; o tempo de hospitalizacao de 24 h. Conclusoes:: Assim como no
reparo das hernias inguinais, a abordagem laparoscopica e segura e efetiva para
as hernias lombares, especialmente se os detalhes anatomicos forem adequadamente
respeitados.
PMID- 28489173
TI - NEW TECHNIQUE FOR OBESITY SURGERY: INTERNAL GASTRIC PLICATION TECHNIQUE USING
INTRAGASTRIC SINGLE-PORT (IGS-IGP) IN EXPERIMENTAL MODEL.
AB - Background: : Bariatric surgery is currently the most effective method to
ameliorate co-morbidities as consequence of morbidly obese patients with BMI over
35 kg/m2. Endoscopic techniques have been developed to treat patients with mild
obesity and ameliorate comorbidities, but endoscopic skills are needed, beside
the costs of the devices. Aim:: To report a new technique for internal gastric
plication using an intragastric single port device in an experimental swine
model. Methods:: Twenty experiments using fresh pig cadaver stomachs in a
laparoscopic trainer were performed. The procedure was performed as follow in ten
pigs: 1) volume measure; 2) insufflation of the stomach with CO2; 3) extroversion
of the stomach through the simulator and installation of the single port device
(Gelpoint Applied Mini) through a gastrotomy close to the pylorus; 4) performance
of four intragastric handsewn 4-point sutures with Prolene 2-0, from the gastric
fundus to the antrum; 5) after the performance, the residual volume was measured.
Sleeve gastrectomy was also performed in further ten pigs and pre- and post
procedure gastric volume were measured. Results:: The internal gastric plication
technique was performed successfully in the ten swine experiments. The mean
procedure time was 27+/-4 min. It produced a reduction of gastric volume of a
mean of 51%, and sleeve gastrectomy, a mean of 90% in this swine model.
Conclusion:: The internal gastric plication technique using an intragastric
single port device required few skills to perform, had low operative time and
achieved good reduction (51%) of gastric volume in an in vitro experimental
model. Racional:: A cirurgia bariatrica e atualmente o metodo mais efetivo para
melhorar as co-morbidades decorrentes da obesidade morbida com IMC acima de 35
kg/m2. Tecnicas endoscopicas foram desenvolvidas para tratar pacientes com
obesidade leve e melhorar as comorbidades, mas habilidades endoscopicas sao
necessarias, alem dos custos. Objetivo:: Relatar uma nova tecnica para a
plicatura gastrica interna utilizando um dispositivo intragastrico de portal
unico em modelo experimental de suinos. Metodos:: Foram realizados 20
experimentos utilizando estomagos de cadaver de porco fresco em um instrutor
laparoscopico. O procedimento foi realizado da seguinte forma em dez porcos: 1)
medida de volume; 2) insuflacao do estomago com CO2; 3) extroversao do estomago
atraves do simulador e instalacao do dispositivo de uma unica via (Gelpoint
Applied Mini) atraves de uma gastrotomia proxima ao piloro; 4) realizacao de
quatro suturas de quatro pontos intra-gastricas com Prolene 2-0, desde o fundo
gastrico ate o antro; 5) medicao do volume residual. A gastrectomia vertical foi
tambem realizada em mais dez suinos e o volume gastrico pre e pos-procedimento
foi medido. Resultados:: A tecnica de plicatura gastrica interna foi realizada
com sucesso nos dez experimentos com suinos. O tempo medio do procedimento foi de
27+/-4 min. Produziu reducao do volume gastrico em media de 51%, e a gastrectomia
vertical em media de 90% neste modelo suino. Conclusao:: A tecnica de plicatura
gastrica interna, utilizando um dispositivo intragastrico de uma unica via,
exigiu poucas habilidades para ser realizada, teve baixo tempo operatorio e
obteve boa reducao (51%) do volume gastrico em um modelo experimental in vitro.
PMID- 28489174
TI - THE IMPACT OF THE MELD SCORE ON LIVER TRANSPLANT ALLOCATION AND RESULTS: AN
INTEGRATIVE REVIEW.
AB - Introduction: Liver transplantation is intended to increase the survival of
patients with chronic liver disease in terminal phase, as well as improved
quality of life. Since the first transplant until today many changes have
occurred in the organ allocation system. Objective: To review the literature on
the Model for End-stage Liver Disease (MELD) and analyze its correlation with
survival after liver transplantation. Method: An integrative literature review in
Lilacs, SciELO, and Pubmed in October 2015, was realized. Were included eight
studies related to the MELD score and its impact on liver transplant. Results:
There was predominance of transplants in male between 45-55 y. The main
indications were hepatitis C, hepatocellular carcinoma and alcoholic cirrhosis.
The most important factors post-surgery were related to the MELD score, the
recipient age, expanded donor criteria and hemotransfusion. Conclusion: The MELD
system reduced the death rate in patients waiting for a liver transplant.
However, this score by itself is not a good predictor of survival after liver
transplantation.
PMID- 28489175
TI - A PICTORIAL PRESENTATION OF ESOPHAGEAL HIGH RESOLUTION MANOMETRY CURRENT
PARAMETERS.
AB - Introduction:: High resolution manometry is the current technology used to the
study of esophageal motility and is replacing conventional manometry in important
centers for esophageal motility with parameters used on esophageal motility,
following the Chicago Classification. This classification unifies high resolution
manometry interpretation and classifies esophageal disorders. Objective:: This
review shows, in a pictorial presentation, the new parameters established by the
Chicago Classification, version 3.0, aimed to allow an easy comprehension and
interpretation of high resolution manometry. Methods:: Esophageal manometries
performed by the authors were reviewed to select illustrative tracings
representing Chicago Classification parameters. Results:: The parameters are:
Esophagogastric Morphology, that classifies this junction according to its
physiology and anatomy; Integrated Relaxation Pressure, that measures the lower
esophageal sphincter relaxation; Distal Contractile Integral, that evaluates the
contraction vigor of each wave; and, Distal Latency, that measures the
peristalsis velocity from the beginning of the swallow to the epiphrenic ampulla.
Conclusion:: Clinical applications of these new concepts is still under
evaluation. Objetivo:: Mostrar, de forma pictorica, os novos parametros
compilados na versao 3.0 da Classificacao de Chicago, buscando facilitar a
compreensao e interpretacao da manometria de alta resolucao. Metodos:: Foram
revistas as manometrias da casuistica dos autores e selecionados os tracados
representativos dos parametros da Classificacao de Chicago. Resultados:: Entre os
parametros apresentados foram considerados a Morfologia da Transicao
Gastroesofagica, que classifica o segmento de acordo com sua fisiologia e
anatomia; a Integral da Pressao de Relaxamento, que mede o relaxamento do
esfincter esofagiano inferior; a Integral Contratil Distal, que avalia o vigor
contratil da onda peristaltica; e, a Latencia Distal, que mede o tempo da
peristalse, desde o inicio da degluticao ate a ampola epifrenica. Conclusao:: A
aplicabilidade clinica desses novos conceitos ainda esta sendo estudada.
PMID- 28489176
TI - BRUNNER GLAND ADENOMA MASQUERADING AS DUODENAL GASTROINTESTINAL STROMAL TUMOR
WITH INTUSSUSCEPTION: CASE REPORT.
PMID- 28489177
TI - MANAGEMENT OF FLAP DEHISCENCE AFTER LiMBERG PROCEDURE FOR RECURRENT PiLONiDAL
DiSEASE BY NEGATiVE PRESSURE WOUND THERAPY (NPWT).
PMID- 28489178
TI - Blood pressure variability in the elderly. Association between postprandial and
sleeping periods.
AB - INTRODUCTION: The variability of arterial blood pressure (BP) is considered an
important cardiovascular risk factor. OBJECTIVE: To verify the possible
associations between the postprandial and the sleeping blood pressure
variability. METHODS: This study evaluated systolic, diastolic, mean, pulse
pressures and heart variability in 69 elderly patients in preprandial,
postprandial and sleeping periods. One 24 hours ambulatory blood pressure
monitoring was used for measurements and the results were showed in the time-rate
index. RESULTS: We observed a decrease in the systolic blood pressure values from
preprandial to postprandial and to the sleeping periods (124.7 +/- 14.6, 113.2 +/
15.3 and 108.5 +/- 13.9mmHg, respectively; p = 0.003). Associations between BP
variability of the postprandial and sleeping periods were obtained for systolic,
diastolic and mean arterial pressure. CONCLUSION: The correlation between
postprandial and sleeping BP variability has rarely been demonstrated in the
literature. These correlations between BP changes after eating and during sleep
might suggest that both events could coexist in other clinical situations.
PMID- 28489179
TI - Analysis of economic impact between the modality of renal replacement therapy.
AB - INTRODUCTION: Chronic kidney disease (CKD) is a major health problem, determining
the reduction in life expectancy and an increased risk of cardiovascular disease.
METHOD: An observational, cohort, retrospective, based on patient's medical
records data with CKD under hemodialysis, peritoneal dialysis and kidney
transplantation in the city of Curitiba, in the period from January to June 2014,
evacuativo the financial impact on the Unified Health System (SUS) and the
supplementary health. RESULTS: The lowest cost of a kidney transplant in the
first year was R$ 40,743.03 when cyclosporine was used and the highest was R$
48,388.17 with the use of tacrolimus. In the second year post-transplant,
hemodialysis and peritoneal dialysis have a higher cost compared to kidney
transplant. Transplantation with deceased donor, treated with tacrolimus: R$
67,023.39; Hemodialysis R$ 71,717.51 and automated peritoneal dialysis automatic
R$ 69,527.03. CONCLUSIONS: After the first two years of renal replacement
therapy, transplantation demonstrates lower costs to the system when compared to
other modalities evaluated. Based on that, this therapy justifies improvements in
government policies in this sector.
PMID- 28489180
TI - Does infection by the hepatitis C virus decrease the response of immunization
against the hepatitis B virus in individuals undergoing dialysis?
AB - INTRODUCTION: Vaccination is the most effective tool in preventing transmission
of Hepatitis B Virus (HBV). The patient with chronic kidney disease (CKD) on
dialysis appear to be at greater risk of becoming infected with this virus and
does not show the same vaccine response when compared to patients without uremia.
OBJECTIVES: To evaluate the results related to the HBV vaccine and identify
factors associated with the response in patients with CKD on hemodialysis.
METHODS: Individuals with HBsAG and negative anti-HBC, under hemodialysis were
assessed in two units of Sao Luis, Maranhao and were undergone full vaccination
schedule for HBV. They were divided in groups: anti-HBs10 mUI/mL and compared as
to age, gender, presence of diabetes mellitus (DM), time on dialysis and anti-HCV
status. Logistic regression analysis was performed to identify factors
independently associated with the vaccine response. p10mUI/Ml (or = 5.239 IC:
1.279-21.459, p = 0.021). CONCLUSION: The rate of vaccine response to HBV in
patients with CKD on dialysis was 70% and the lack of anti-HCV infection was
associated with seroconversion of anti-HBs suggesting that infection by the
hepatitis C virus may be a factor that decreases the response of the HBV vaccine
in dialysis CKD patients.
PMID- 28489181
TI - Early postoperative parathormone sampling and prognosis after total
parathyroidectomy in secondary hyperparathyroidism.
AB - INTRODUCTION: There is possibility of a supernumerary hyperplastic parathyroid
gland in dialysis patients after total parathyroidectomy and autograft in
dialysis patients. OBJECTIVE: To test if the early postoperative measure of
parathyroid hormone (PTH) can identify persistent hyperparathyroidism. METHODS: A
prospective cohort of dialysis patients submitted to parathyroidectomy had PTH
measured up to one week after operation. The absolute value and the relative
decrease were analyzed according to clinical outcome of satisfactory control of
secondary hyperparathyroidism or persistence. RESULTS: Of 51 cases, preoperative
PTH varied from 425 to 6,964 pg/mL (median 2,103 pg/mL). Postoperatively, PTH was
undetectable in 28 cases (54.9%). In eight individuals (15.7%) the PTH was lower
than 16 pg/mL, in 10 (19.6%) the PTH values were between 16 and 87pg/mL, and in
five (9.8%), PTH was higher than 87 pg/mL. Undetectable PTH was more common in
patients with preoperative PTH below the median (p = 0.0002). There was a
significant correlation between preoperative PTH and early postoperative PTH
(Spearman R = 0.42, p = 0.002). A relative decrease superior to 95% was
associated to satisfactory clinical outcome. A relative decrease less than 80%
was associated to persistent disease, despite initial postoperative hypocalcemia.
CONCLUSION: Measurement of PTH in the first days after parathyroidectomy in
dialysis patients may suggest good clinical outcome if a decrease of at least 95%
of the preoperative value is observed. Less than 80% PTH decrease is highly
suggestive of residual hyperfunctioning parathyroid tissue with persistent
hyperparathyroidism, and an early reintervention may be considered.
PMID- 28489182
TI - Acute effects of intradialytic aerobic exercise on solute removal, blood gases
and oxidative stress in patients with chronic kidney disease.
AB - INTRODUCTION: Hemodialysis contributes to increased oxidative stress and induces
transitory hypoxemia. Compartmentalization decreases the supply of solutes to the
dialyzer during treatment. The aim of this study was to investigate the acute
effects of intradialytic aerobic exercise on solute removal, blood gases and
oxidative stress in patients with chronic kidney disease during a single
hemodialysis session. METHODS: Thirty patients were randomized to perform aerobic
exercise with cycle ergometer for lower limbs during 30 minutes with intensity
between 60-70% of maximal heart rate, or control group (CG). Blood samples were
collected prior to and immediately after exercise or the equivalent time in CG.
Analysis of blood and dialysate biochemistry as well as blood gases were
performed. Mass removal and solute clearance were calculated. Oxidative stress
was determined by lipid peroxidation and by the total antioxidant capacity.
RESULTS: Serum concentrations of solutes increased with exercise, but only
phosphorus showed a significant elevation (p = 0.035). There were no significant
changes in solute removal and in the acid-base balance. Both oxygen partial
pressure and saturation increased with exercise (p = 0.035 and p = 0.024,
respectivelly), which did not occur in the CG. The total antioxidant capacity
decreased significantly (p = 0.027). CONCLUSION: The acute intradialytic aerobic
exercise increased phosphorus serum concentration and decreased total antioxidant
capacity, reversing hypoxemia resulting from hemodialysis. The intradialytic
exercise did not change the blood acid-base balance and the removal of solutes.
PMID- 28489183
TI - Frequency and factors associated with falls in adults aged 55 years or more.
AB - OBJECTIVE: The objective of this study is to analyze the frequency and factors
associated with falls in adults aged 55 years or more. METHODS: This is a study
inserted into another population-based study with representative sample of
persons aged 40 years or more of the urban area in a medium-sized municipality of
the State of Parana, Brazil, in 2011. That study obtained demographic and
socioeconomic data and characteristics related to life habits, health conditions,
and functional capacity (n = 1,180). In 2012, we selected all persons aged 55
years or more (n = 501). We have estimated grip strength and the occurrence of a
fall since the last interview in 80.6% of the adults. The crude and adjusted odds
ratios (OR) have been calculated by logistic regression according to a
hierarchical model. RESULTS: The rate of fall was 24.3%. After adjustments, we
could observe higher chances of falls among women (OR = 3.10; 95%CI 1.79-5.38),
among persons aged 65 years or more (OR = 2.39; 95%CI 1.45-3.95), with poor sleep
quality (OR = 1.78; 95%CI 1.08-2.93), and with low grip strength (OR = 2.31;
95%CI 1.34-3.97). CONCLUSIONS: Poor sleep quality and low muscle strength can be
indicators of increased risk of falls and need assessments and interventions
aimed at preventing them. OBJETIVO: Analisar a frequencia e fatores associados a
ocorrencia de quedas em adultos de 55 anos ou mais. METODOS: Estudo inserido em
outro de base populacional com amostra representativa de pessoas com 40 anos ou
mais da area urbana de municipio de medio porte do Parana em 2011. Foram obtidos
dados demograficos e socioeconomicos, caracteristicas referentes aos habitos de
vida, as condicoes de saude e a capacidade funcional (n = 1.180). Em 2012,
selecionaram-se todas as pessoas com idade igual ou superior a 55 anos (n = 501).
Foram estimadas a forca de preensao palmar e a ocorrencia de queda desde a ultima
entrevista em 80,6% delas. Foram calculadas odds ratios (OR) brutas e ajustadas
por regressao logistica segundo modelo hierarquizado. RESULTADOS: A frequencia de
queda foi de 24,3%. Apos ajustes, observaram-se chances maiores de queda entre
mulheres (OR = 3,10; IC95% 1,79-5,38), entre pessoas com idade igual ou superior
a 65 anos (OR = 2,39; IC95% 1,45-3,95), com qualidade do sono ruim (OR = 1,78;
IC95% 1,08-2,93) e com baixa forca de preensao palmar (OR = 2,31; IC95% 1,34
3,97). CONCLUSOES: Qualidade ruim do sono e a baixa forca muscular podem ser
indicadores de maior risco de quedas e merecem avaliacoes e intervencoes visando
a prevencao desse agravo.
PMID- 28489184
TI - Hepatitis C among blood donors: cascade of care and predictors of loss to follow
up.
AB - OBJECTIVE: To investigate the HCV cascade of care and to identify the factors
associated with loss or absence to follow-up of patients identified as infected
with hepatitis C through blood donation. METHODS: Blood donors from 1994 to 2012,
identified with positive anti- HCV by enzyme immunoassay and immunoblot tests
were invited to participate in the study, through letters or phone calls.
Patients who agreed to participate were interviewed and their blood samples were
collected for further testing. The following variables were investigated:
demographic data, data on comorbidities and history concerning monitoring of
hepatitis C. Multiple regression analysis by Poisson regression model was used to
investigate the factors associated with non-referral for consultation or loss of
follow-up. RESULTS: Of the 2,952 HCV-infected blood donors, 22.8% agreed to
participate: 394 (58.2%) male, median age 48 years old and 364 (53.8%) Caucasian.
Of the 676 participants, 39.7% did not receive proper follow-up or treatment
after diagnosis: 45 patients referred not to be aware they were infected, 61 did
not seek medical attention and 163 started a follow-up program, but were non
adherent. The main reasons for inadequate follow-up were not understanding the
need for medical care (71%) and health care access difficulties (14%). The
variables showing a significant association with inadequate follow-up after
multiple regression analysis were male gender (PR = 1.40; 95%CI 1.15-1.71), age
under or equal to 50 years (PR = 1.36; 95%CI 1.12-1.65) and non-Caucasians (PR =
1.53; 95%CI 1.27-1.84). CONCLUSIONS: About 40.0% of patients did not receive
appropriate follow-up. These data reinforce the need to establish strong links
between primary care and reference centers and the need to improve access to
specialists and treatments.
PMID- 28489185
TI - Risk factors associated with multidrug-resistant tuberculosis in Espirito Santo,
Brazil.
AB - OBJECTIVE: To analyze the prevalence and factors associated with multidrug
resistant tuberculosis in Espirito Santo, Brazil. METHODS: This is a cross
sectional study of cases of tuberculosis tested for first-line drugs (isoniazid,
rifampicin, pyrazinamide, ethambutol, and streptomycin) in Espirito Santo between
2002 and 2012. We have used laboratory data and registration of cases of
tuberculosis - from the Sistema Nacional de Agravos de Notificacao and Sistema
para Tratamentos Especiais de Tuberculose. Individuals have been classified as
resistant and non-resistant and compared in relation to the sociodemographic,
clinical, and epidemiological variables. Some variables have been included in a
logistic regression model to establish the factors associated with resistance.
RESULTS: In the study period, 1,669 individuals underwent anti-tuberculosis drug
susceptibility testing. Of these individuals, 10.6% showed resistance to any anti
tuberculosis drug. The rate of multidrug resistance observed, that is, to
rifampicin and isoniazid, has been 5%. After multiple analysis, we have
identified as independent factors associated with resistant tuberculosis: history
of previous treatment of tuberculosis [recurrence (OR = 7.72; 95%CI 4.24-14.05)
and re-entry after abandonment (OR = 3.91; 95%CI 1.81-8.43)], smoking (OR = 3.93;
95%CI 1.98-7.79), and positive culture for Mycobacterium tuberculosis at the time
of notification of the case (OR = 3.22; 95%CI 1.15-8.99). CONCLUSIONS: The
partnership between tuberculosis control programs and health teams working in the
network of Primary Health Care needs to be strengthened. This would allow the
identification and monitoring of individuals with a history of previous treatment
of tuberculosis and smoking. Moreover, the expansion of the offer of the culture
of tuberculosis and anti-tuberculosis drug susceptibility testing would provide
greater diagnostic capacity for the resistant types in Espirito Santo. OBJETIVO:
Analisar a prevalencia e fatores associados a tuberculose resistente no Espirito
Santo. METODOS: Estudo transversal dos casos de tuberculose testados para
farmacos de primeira linha (isoniazida, rifampicina, pirazinamida, etambutol e
estreptomicina) no Espirito Santo entre 2002 e 2012. Foram utilizados dados
laboratoriais e de registro de casos de tuberculose - Sistema Nacional de Agravos
de Notificacao e Sistema para Tratamentos Especiais de Tuberculose. Os individuos
foram classificados em resistentes e nao resistentes, e comparados para variaveis
sociodemograficas, clinicas e epidemiologicas. Algumas variaveis foram inclusas
em um modelo de regressao logistica para estabelecimento de fatores associados a
resistencia. RESULTADOS: No periodo do estudo, 1.669 individuos tiveram o teste
de sensibilidade aos farmacos antituberculose realizado. Destes, 10,6%
apresentaram resistencia a qualquer droga antituberculose. A taxa de
multirresistencia observada, isto e, a rifampicina e isoniazida, foi de 5%. Apos
a analise multipla, foram identificados como fatores associados independentes
para tuberculose resistente: historia de tratamento previo para tuberculose
[Recidiva (OR = 7,72; IC95% 4,24-14,05) e reingresso apos abandono (OR = 3,91;
IC95% 1,81-8,43)], tabagismo (OR = 3,93; IC95% 1,98-7,79) e cultura positiva para
Mycobacterium tuberculosis no momento da notificacao do caso (OR = 3,22; IC95%
1,15-8,99). CONCLUSOES: E necessario o fortalecimento da parceria entre os
programas de controle de tuberculose e as equipes de saude que atuam na rede de
Atencao Primaria a Saude. Isso possibilitaria identificar e acompanhar individuos
com historia de tratamento previo para tuberculose e tabagismo. Alem disso, a
ampliacao da oferta de cultura e Teste de Sensibilidade a farmacos
antituberculose proporcionaria maior capacidade diagnostica para as formas
resistentes no Espirito Santo.
PMID- 28489186
TI - Overweight, obesity, steps, and moderate to vigorous physical activity in
children.
AB - OBJECTIVE: The objective of this study is to establish cutoff points for the
number of steps/day and minutes/day of moderate to vigorous physical activity in
relation to the risk of childhood overweight and obesity and their respective
associations. In addition, we aim to identify the amount of steps/day needed to
achieve the recommendation of moderate to vigorous physical activity in children
from Sao Caetano do Sul. METHODS: In total, 494 children have used an
accelerometer to monitor steps/day and the intensity of physical activity
(min/day). The moderate to vigorous physical activity has been categorized
according to the public health recommendation (<= 60 versus > 60 min/day).
Overweight or obesity is defined as body mass index > +1 SD, based on reference
data from the World Health Organization. The data on family income, education of
parents, screen time, diet pattern, and sedentary time have been collected by
questionnaires. Logistic regression and Receiver Operating Characteristic curves
have been constructed. RESULTS: On average, boys walked more steps/day (1,850)
and performed more min/day of moderate to vigorous physical activity (23.1) than
girls. Overall, 51.4% of the children have been classified as eutrophic and 48.6%
as overweight or obese. Eutrophic boys walked 1,525 steps/day and performed 18.6
minutes/day more of moderate to vigorous physical activity than those with
overweight/obesity (p < 0.05). The same has not been found in girls (p > 0.05).
The cutoff points to prevent overweight and obesity in boys and girls were 10,500
and 8,500 steps/day and 66 and 46 min/day of moderate to vigorous physical
activity, respectively. The walking of 9,700 steps/day for boys and 9,400
steps/day for girls ensures the scope of the recommendation of moderate to
vigorous physical activity. CONCLUSIONS: In boys, steps/day and moderate to
vigorous physical activity have been negatively associated with body mass index,
regardless of race, family income, education of parents, screen time, diet
pattern, and sedentary time. We suggest, for steps/day and moderate to vigorous
physical activity, studies with different ages and populations, with different
designs, so as to inform the cause and effect relationship with various health
parameters. OBJETIVO: Estabelecer pontos de corte para o numero de passos/dia e
min/dia de atividade fisica com intensidade moderada a vigorosa em relacao ao
risco do excesso de peso e obesidade infantil e suas respectivas associacoes.
Alem de identificar a quantidade de passos/dia necessarios para atingir a
recomendacao de atividade fisica de moderada a vigorosa em criancas de Sao
Caetano do Sul. METODOS: No total, 494 criancas usaram acelerometro para
monitorar os passos/dia e a intensidade da atividade fisica (min/dia). A
atividade fisica de moderada a vigorosa foi categorizada de acordo com a
recomendacao de saude publica (<= 60 versus > 60 min/dia). Excesso de peso ou
obesidade foi definido como indice de massa corporal > +1 DP, com base nos dados
de referencia da Organizacao Mundial de Saude. Renda familiar, escolaridade dos
pais, tempo de tela, padrao de dieta, e tempo sedentario foram coletados por
questionarios. Foram construidas curvas Receiver Operating Characteristic e
regressao logistica. RESULTADOS: Em media, os meninos realizaram mais passos/dia
(1.850) e min/dia de atividade fisica de moderada a vigorosa (23,1) do que as
meninas. No geral, 51,4% das criancas foram classificadas como eutroficas e 48,6%
com excesso de peso ou obesidade. Meninos eutroficos realizavam 1.525 passos/dia
e 18,6 min/dia de atividade fisica de moderada a vigorosa a mais do que aqueles
com excesso de peso/obesidade (p < 0,05). O mesmo nao foi encontrado nas meninas
(p > 0,05). Os pontos de corte para evitar excesso de peso e obesidade nos
meninos e meninas foram 10.500 e 8.500 passos/dia e 66 e 46 min/dia de atividade
fisica de moderada a vigorosa, respectivamente. A realizacao de 9.700 passos/dia
(meninos) e 9.400 passos/dia (meninas) garante o alcance da recomendacao de
atividade fisica de moderada a vigorosa. CONCLUSOES: Nos meninos, passos/dia e
atividade fisica de moderada a vigorosa foram negativamente associados com o
indice de massa corporal, independentemente da raca, renda familiar, escolaridade
dos pais, tempo de tela, padrao de dieta e tempo sedentario. Sugere-se para
passos/dia e atividade fisica de moderada a vigorosa, estudos em diversas idades
e populacoes, com diferentes delineamentos, para assim informar a relacao causa e
efeito com diversos parametros de saude.
PMID- 28489187
TI - Teamwork: relevance and interdependence of interprofessional education.
AB - OBJECTIVE: Determine the perception of university students regarding
interprofessional and interdependent work between team members in their inclusion
in primary care. METHODS: Analytical cross-sectional study. The sampling had a
probabilistic, stratified random type with 95% confidence and 5% margin of error.
Seven-hundred and four students of Public Universities in Santiago (Chile)
answered self-administered questionnaire. RESULTS: Ninety-seven point eight of
students say that interprofessional work is important; 27.1% of them declare that
their university did not seem to show that their study plans were important. The
professionals listed as most important in teams are physicians and nurses.
CONCLUSIONS: Spaces for development and institutional support are key elements to
promote interprofessional work. If this competence can involve each academic unit
in their different formative spaces there will be a significant contribution to
said promotion. Teamwork is a pending task. OBJETIVO: Determinar la percepcion de
estudiantes universitarios respecto al trabajo interprofesional e
interdependencia entre los miembros del equipo en su insercion en la atencion
primaria. METODOS: Estudio de tipo analitico y transversal. El muestreo fue de
tipo aleatorio, probabilistico estratificado con un 95% de confianza y un 5% de
margen de error. Se utilizo un cuestionario auto-administrado en 704 estudiantes
de Universidades del Estado en Santiago de Chile. RESULTADOS: Un 97,8% de los
estudiantes opinan que el trabajo interprofesional es importante; un 27,1% de
ellos declara que su universidad no le ha entregado importancia en sus planes de
estudios. Los profesionales mencionados como mas importantes en el equipo son los
medicos y enfermeras. CONCLUSIONES: Espacios de desarrollo y respaldo
institucional son elementos claves para promover el trabajo interprofesional. Que
esta competencia logre involucrar a cada unidad academica en sus diferentes
espacios formativos sera un aporte significativo en aquello. Trabajo en equipo es
una tarea pendiente.
PMID- 28489188
TI - Cytogenotoxicity of rice crop water after application of the tricyclazole
fungicide.
AB - Tricyclazole is currently one of the fungicides recommended for the treatment of
diseases in irrigated rice. However, there is relatively little information on
its cytotoxic and genotoxic potential. The objective of this study was to
evaluate the cytotoxicity and genotoxicity of rice crop water after apllication
of the tricyclazole fungicide through the Allium cepa L. test. The rice crop
water samplings were collected before and 1, 15 and 30 days after application of
the fungicide in rice plant shoots. The Allium cepa roots were placed in contact
with the rice crop water to check for possible chromosomal abnormalities and
mitotic index of the bioindicators meristematic cells. The data obtained by the
Allium cepa test indicates that the application of the tricyclazole fungicide
leads to an increase in the genotoxic activity in the rice crop water, through
the appearance of chromosomal abnormalities, without, however, causing
significant effects on the mitotic index. The major chromosomal alterations
observed were anaphasic and telophasic bridges and laggard chromosomes.
PMID- 28489189
TI - Vitamin E and organic selenium for broilers from 22 to 42 days old: performance
and carcass traits.
AB - This study was conducted to evaluate the effect of vitamin E and selenium on
performance, viability, productive efficiency, and yields of carcass, major cuts,
and organs of broilers from 22 to 42 days submitted to cyclic-heat stress. The
experimental design was randomized blocks, in a 2 * 3 factorial arrangement with
two levels of selenium (0.1 and 0.3 mg/kg) and three levels of vitamin E (300,
400, and 500 mg/kg), plus a control treatment. Animals were submitted to a
natural condition of high cyclic temperature. Organic selenium levels of 0.1 and
0.3 mg/kg associated with 300, 400, and 500 mg/kg of vitamin E were tested. The
level of vitamin E did not affect the performance or production efficiency of
broilers in the period from 22 to 33 days and 22 to 42 days. However, the
selenium inclusion level of 0.3 mg/kg improved the viability in both phases. The
yields of carcass, major cuts, intestine, and heart were not influenced by the
levels of selenium and vitamin E, whereas abdominal fat for the selenium level
0.1 mg/kg decreased linearly with the inclusion in vitamin E.
PMID- 28489190
TI - Growth, photosynthetic pigments and production of essential oil of long-pepper
under different light conditions.
AB - Piper hispidinervum C. DC. is popularly known as long-pepper and it owns a
commercial value due to the essential oil it produces. Long-pepper oil is rich in
safrole and eugenoln components that have insecticidal, fungicidal and
bactericidal activity. It has been establish that to medicinal plants light
influences not only growth but also essential oil production. The growth, the
content of photosynthetic pigments and the essential oil production of Piper
hispidinervum at greenhouses with different light conditions was evaluated. The
treatments were characterized by cultivation of plants for 180 days under
different light conditions, produced by shading greenhouses with 50% and 30% of
natural incident irradiance, two colored shading nets red (RN) and blue (BN) both
blocking 50% of the incident radiation and one treatment at full-sun (0% of
shade). The results showed that the treatments of 50% shade and RN and BN were
the ones which stimulated the greater growth. Blue and red light also had the
best production of photosynthetic pigments. Essential oil yielded more under full
sun therefore this is the most indicated condition to produce seedlings for the
chemical and pharmaceutical industry.
PMID- 28489191
TI - Pathogenic Vibrio species isolated from estuarine environments (Ceara, Brazil) -
antimicrobial resistance and virulence potential profiles.
AB - Detection of virulent strains associated with aquatic environment is a current
concern for the management and control of human and animal health. Thus, Vibrio
diversity was investigated in four estuaries from state of Ceara (Pacoti, Choro,
Pirangi and Jaguaribe) followed by antimicrobial susceptibility to different
antimicrobials used in aquaculture and detection of main virulence factors to
human health. Isolation and identification were performed on TCBS agar (selective
medium) and dichotomous key based on biochemical characteristics, respectively.
Nineteen strains of genus Vibrio were catalogued. Vibrio parahaemolyticus (Choro
River) and V. alginolyticus (Pacoti River) were the most abundant species in the
four estuaries. All strains were submitted to disk diffusion technique (15
antimicrobials were tested). Resistance was found to: penicillin (82%),
ampicillin (54%), cephalotin (7%), aztreonan (1%), gentamicin, cefotaxime and
ceftriaxone (0.5%). Five pathogenic strains were chosen to verification of
virulence factors. Four estuaries showed a high abundance of species. High number
of tested positive strains for virulence is concerning, since some of those
strains are associated to human diseases, while others are known pathogens of
aquatic organisms.
PMID- 28489192
TI - A new approach to feed frequency studies and protein intake regulation in
juvenile pirarucu.
AB - This study aimed to investigate pirarucu's (Arapaima gigas) ability to trigger a
self-feeding system to regulate protein intake between two standard diets that
contained 39% and 49% of crude protein. The same system allowed the evaluation of
daily feeding and locomotor activity rhythms. Eighteen fish (654.44+/-26.85g)
were distributed into six 250 L tanks (3 fish/tank). Fish had free access to both
diets (39% vs. 49% protein) by feeders (2 per tank), adapted to be activated by
fish themselves. This system was connected to a computer system. After an
adaptation period, fish learned to activate feeders and the mean food intake
recorded was 2.14% of their body weight on a daily basis. Fish showed feeding
(72.48%) and locomotor (72.49%) activity predominantly during the daytime, and
daily variations of choice between diets, but fixed a protein intake feeding
target at 44.53%. These results should be considered when discussing feeding
behavior, feeding schedules and diet intake regulations.
PMID- 28489193
TI - Soluble amino acid profile, mineral nutrient and carbohydrate content of maize
kernels harvested from plants submitted to ascorbic acid seed priming.
AB - Both the scientific community and society have shown interest in improving the
content of amino acids, carbohydrates and mineral nutrients in maize because it
represents an important staple food in many developing countries. Earlier studies
demonstrated that the treatment of seeds using ascorbic acid (AsA-seed priming)
enhanced soluble carbohydrates, proteins and soluble amino acids for other
species. AsA seed priming in maize showed the potential for reducing abiotic
stresses. The effects on grain quality have not been previously demonstrated.
This study investigated the impacts of AsA seed priming on maize kernel quality
of seeds produced by the plants generated from the primed seeds, based on the
amino acid profile and carbohydrate and mineral nutrient contents. AsA seed
priming improved the maize kernel quality with respect to the ascorbate content,
boron allocation, total carbohydrate content and increased soluble amino acid
levels, including serine, tyrosine, alanine, valine, glutamate, arginine,
proline, aspartate, lysine and isoleucine, whereas soluble methionine was
decreased. Therefore, AsA seed priming can represent a potential technique for
improving maize grain quality.
PMID- 28489194
TI - Antiproliferative activity in tumor cell lines, antioxidant capacity and total
phenolic, flavonoid and tannin contents of Myrciaria floribunda.
AB - Myrciaria floribunda (H. West ex Willd.) O. Berg, Myrtaceae, is a native plant
species of the Atlantic Rain Forest, from north to south of Brazil. The
lyophilized ethyl acetate extract from the leaves of M. floribunda was
investigated for its antiproliferative activity in tumor cell lines, antioxidant
capacity and its total phenolic, flavonoid and tannin contents. Antiproliferative
activity was tested in vitro against seven human cancer cells and against
immortalized human skin keratinocytes line (HaCat, no cancer cell). Antioxidant
activity was determined using 1-diphenyl-2-picrylhydrazyl (DPPH) radical
scavenging and oxygen radical absorbing capacity (ORAC) assays and total
phenolic, flavonoid and tannin contents were determined by spectrophotometric
techniques. Ethyl acetate extract of M. floribunda exhibited antiproliferative
activity against cancer cell lines with total growth inhibition (TGI) between
69.70 and 172.10 ug/mL. For HaCat cell, TGI value was 213.60 ug/mL. M. floribunda
showed a strong antioxidant potential: EC50 of 45.89+/-0.42 ug/mL and 0.55+/-0.05
mmol TE/g for DPPH and ORAC, respectively. Total phenolic content was 0.23+/
0.013g gallic acid equivalents (GAE)/g extract and exhibited 13.10+/-1.60% of
tannins content. The content of flavonoid was 24.08+/-0.44% expressed as rutin
equivalents. These results provide a direction for further researches about the
antitumoral potential of M. floribunda.
PMID- 28489195
TI - BEEF TALLOW AND EMULSIFIER IN GROWING-FINISHING PIG DIETS.
AB - Two trials were aimed to evaluate beef tallow in diets with and without
emulsifier on performance of pigs at growing-finishing phases. In the first
trial, 15 barrows (22.03+/-0.62 kg) were distributed among three treatments:
reference diet; test diet 1 (5% beef tallow) and test diet 2 (10% beef tallow).
Beef tallow presented average value of 7130.97 kcal ME/kg. For the performance
trail, 30 barrows (24.85+/-1.18 kg) were distributed among five treatments: T1 -
diet with soybean oil and 3230 kcal ME /kg; T2 - diet with beef tallow and 3230
kcal ME/kg; T3 - diet with beef tallow and 3080 kcal ME/kg; T4 - diet with beef
tallow, 3080 kcal/kg and 0.1% emulsifier; T5 - diet with beef tallow, 2930 kcal
ME/kg and 0.1% emulsifier. Feed conversion was worse in animals fed diet with
3080 kcal ME/kg containing beef tallow and with 2930 kcal ME/kg with beef tallow
and emulsifier. For economic availability, animals fed diet with beef tallow and
3230 kcal ME/kg and those fed diet with 3080 kcal ME/kg containing beef tallow
and emulsifier, did not differ from animals fed diet with soybean oil, which
enables the reduction up to 150 kcal ME/kg be compensated by emulsifier addition.
PMID- 28489196
TI - Parasite infracommunities of Leporinus friderici : A comparison of three
tributaries of the Jurumirim Reservoir in southeastern Brazil.
AB - The degradation and homogenization of natural habitats is considered a major
cause of biotic homogenization. Many studies have been undertaken on the effects
of dams on aquatic wildlife, in particular fish assemblages. But how do dams
affect the parasitic fauna of such fish? The aim of the present study was to
examine parasitic similarity, comparing the diversity and structure of parasite
communities of Leporinus friderici (Characiformes, Anostomidae) in three upstream
tributaries under the influence of the Jurumirim Dam on the Upper Paranapanema
River in southeastern Brazil. The present study did not find any significant
differences in parasite communities among populations of L. friderici in the
three upstream tributaries. This result highlights that dams promote and
facilitate the dispersal of organisms between localities, and therefore the
spatial homogenization of parasite communities. Overall, the results suggest that
fish parasite assemblages can provide suitable data for evaluating biotic
homogenization caused by dams.
PMID- 28489197
TI - Population dynamics of Rimapenaeus constrictus (Stimpson, 1874) (Penaeoidea) on
the southeastern Brazilian coast: implications for shrimp fishing management from
a 5-year study on a bycatch species.
AB - This is the first study to evaluate in broad spatiotemporal scales the growth
parameters and population structure of Rimapenaeus constrictus, a barely damaged
species composing the bycatch from shrimp fishing in the Western Atlantic. The
abundance and size-class frequency distribution, growth, longevity and sex ratio
were evaluated from monthly samples obtained in the northern littoral of Sao
Paulo state from Jan/1998 to Jun/2003. We measured 5,812 individuals in which the
sex ratio was skewed toward females; this was more evident in size classes
greater than 10 mm in CL (carapace length) (binomial test, p<0.05). We selected
16 growth cohorts of females, and 8 of males, the majority consisting of younger
individual cohorts excluded from the fisheries closure period. Growth estimates
resulted in a CLinfinity of 17.42 mm, a growth coefficient of 0.008 and a
longevity of 579 days (1.60 year) for females, as well as a CLinfinity of 16.3
mm, a growth coefficient of 0.01 and a longevity of 425 days (1.17 year) for
males. Our results provide information of incontestable relevance to our
knowledge of fishing management. We therefore strongly recommend that the
fisheries closure period be changed to protect this species' recruitment period
and consequently its adult individuals.
PMID- 28489198
TI - Are the dinosauromorph femora from the Upper Triassic of Hayden Quarry (New
Mexico) three stages in a growth series of a single taxon?
AB - The lagerpetid Dromomeron romeri and the theropod Tawa hallae are two
dinosauromorphs from the Norian (Upper Triassic) of the Chinle Formation,
situated in New Mexico, USA. However, a recent study suggests the inclusion of
the holotype of D. romeri (GR 218) and paratype (GR 155) and referred (GR 235)
specimens of T. hallae in an ontogenetic series of a single species. The
specimens GR 218 and GR 155 include just an isolated femur, while GR235 includes
femora, pelvis and tail. The inclusion of the specimens in an unique ontogenetic
series relies on the putative immature condition and plastic deformation of the
specimen GR 218. However, as observed here, the disparity between the femora of
D. romeri and T. hallae is considerably higher than those expected from the
ontogenetic variance in dinosauromorphs. In addition, D. romeri shares an unique
suite of traits with Dromomeron gigas, a species known from a mature specimen.
Therefore, the high disparity between D. romeri and T. hallae, lack of traits
shared solely between the three femora, and a suite of traits shared between D.
romeri and D. gigas, precludes the inclusion of the three femora from Hayden
Quarry in a growth series of a single taxon.
PMID- 28489199
TI - Compatibility of Azospirillum brasilense and Pseudomonas fluorescens in growth
promotion of groundnut ( Arachis hypogea L.).
AB - We attempted to study the compatibility among plant beneficial bacteria in the
culture level by growing them near in the nutrient agar plates. Among all the
bacteria tested, Rhizobium was found to inhibit the growth of other bacteria.
From the compatible group of PGPR, we have selected one biofertilizer
(Azospirillum brasilense strain TNAU) and one biocontrol agent (Pseudomonas
fluorescens strain PF1) for further studies in the pot culture. We have also
developed a bioformulation which is talc powder based, for individual bacteria
and mixed culture. This formulation was used as seed treatment, soil application,
seedling root dip and foliar spray in groundnut crop in vitro germination
conditions. A. brasilense was found to enhance the tap root growth and P.
fluorescens, the lateral root growth. The other growth parameters like shoot
growth, number of leaves were enhanced by the combination of both of the bacteria
than their individual formulations. Among the method of application tested in our
study, soil application was found to be the best in yielding better results of
plant growth promotion.
PMID- 28489200
TI - A new species of Tereancistrum (Monogenea, Dactylogyridae) from the gills of
three Leporinus species (Characiformes, Anostomidae) and a revised description of
Tereancistrum parvus.
AB - The present study describes Tereancistrum flabellum n. sp. (Dactylogyridae,
Ancyrocephalinae) from the gills of the anostomid fishes Leporinus friderici,
Leporinus amblyrhynchus and Leporinus elongatus from two freshwater ecosystems in
the south east of Brazil. This new species is mainly characterized by the
morphology of the copulatory complex (such as the MCO base formed by two fan
shaped structures, and accessory piece flattened, curved, rigid and channeled), a
dorsal anchor with a well-developed superficial and inconspicuous deep root, and
the shape of the accessory anchor sclerite with small spathulate termination.
Tereancistrum flabellum n. sp. is the first record of a dactylogyrid from L.
amblyrhynchus. The description of Tereancistrum parvus is also emended to correct
and complement previous descriptions and the species is reported for the first
time in Schizodon nasutus.
PMID- 28489201
TI - Water temperature, body mass and fasting heat production of pacu (Piaractus
mesopotamicus).
AB - Knowledge on fasting heat production (HEf) of fish is key to develop
bioenergetics models thus improving feeding management of farmed species. The
core of knowledge on HEf of farmed, neotropical fish is scarce. This study
assessed the effect of body mass and water temperature on standard metabolism and
fasting heat production of pacu, Piaractus mesopotamicus, an omnivore,
Neotropical fresh water characin important for farming and fisheries industries
all through South American continent. An automated, intermittent flow
respirometry system was used to measure standard metabolic rate (SMR) of pacu (17
- 1,050 g) at five water temperatures: 19, 23, 26, 29 and 33 degrees C. Mass
specific SMR increased with increasing water temperature but decreased as
function of body mass. The allometric exponent for scaling HEf was 0.788, and
lied in the range recorded for all studied warm-water fish. The recorded van't
Hoff factor (Q10) for pacu (2.06) shows the species low response to temperature
increases. The model HEf = 0.04643*W0.7882*T1.837 allows to predict HEf (kJ d-1)
from body mass (W, kg) and water temperature (T, degrees C), and can be used in
bioenergetical models for the species.
PMID- 28489202
TI - Diversity and distribution of epiphytic bromeliads in a Brazilian subtropical
mangrove.
AB - It is not unusual to find epiphytic bromeliads in mangroves, but most studies on
mangrove vegetation do not record their presence. This study aimed to evaluate
the diversity and distribution of epiphytic bromeliads in a subtropical mangrove.
The richness, abundance and life form (atmospheric and tank) of bromeliads were
recorded and compared among host tree species and waterline proximity. The
effects of diameter and height of host trees on the abundance of bromeliads were
also assessed. The mangrove was composed of Avicennia schaueriana, Laguncularia
racemosa and Rhizophora mangle. We recorded seven bromeliad species of the genera
Tillandsia and Vriesea. The waterline proximity did not affect the abundance or
diversity of bromeliads, but atmospheric forms were predominant near the
waterline, whereas tank bromeliads were more frequent in the interior of the
mangrove. The three mangrove species hosted bromeliads, but L. racemosa was the
preferred host. The species composition showed that the distribution of
bromeliads is more related to the host species than to the distance from the
waterline. Bromeliad abundance increased with tree size. Bromeliads can be
biological indicators of ecosystem health; therefore, inventories and host tree
preferences are necessary knowledge for an adequate management of sensitive
ecosystems as mangroves.
PMID- 28489203
TI - Evaluation of methods for the quantification of ether extract contents in forage
and cattle feces.
AB - The objective of this study was to compare the estimates of ether extract (EE)
contents obtained by the Randall method and by the high-temperature method of the
American Oil Chemist's Society (AOCS; Am 5-04) in forages (n = 20) and cattle
feces (n = 15). The EE contents were quantified by using the Randall extraction
or AOCS method and XT4 filter bags or cartridges made of qualitative filter paper
(80 g/m2) as containers for the samples. It was also evaluated the loss of
particles, and concentration of residual chlorophyll after extraction and the
recovery of protein and minerals in the material subjected to extraction.
Significant interaction was observed between extraction method and material for
EE contents. The EE estimates using the AOCS method were higher, mainly in
forages. No loss of particles was observed with different containers. The
chlorophyll contents in the residues of cattle feces were not affected by the
extraction method; however, residual chlorophyll was lower using the AOCS method
in forages. There was complete recovery of the protein and ash after extraction.
The results suggest that AOCS method produces higher estimates of EE contents in
forages and cattle feces, possibly by providing greater extraction of non-fatty
EE.
PMID- 28489204
TI - Have the current and promising therapeutic options changed the surgeon's role in
the treatment of pancreatic cancer?
PMID- 28489205
TI - Profile of the appendectomies performed in the Brazilian Public Health System.
AB - Objective: to analyze the profile of appendectomies performed in the Brazilian
Public Health System (SUS) and to compare the laparoscopic and laparotomic
techniques of appendectomy. Methods: This work used information from DataSus from
2008 to 2014 (http://datasus.saude.gov.br). We compared the data of patients
submitted to laparotomic appendectomy with those submitted to laparoscopic one.
Results: when comparing the total growth of appendectomies, the laparoscopic
route increased 279.7%, while the increase in laparotomic surgery was 25% (p
<0.001) in the study period. With regard to medical and hospital costs,
laparoscopic appendectomy accounted for only 2.6% of the total expenditure on
appendectomies performed by the Unified Health System (SUS) hospitals, with an
average cost 7.6% lower than that of laparotomy procedures, but without
statistical significance. The mortality rate was 57.1% lower in the laparoscopic
approach when compared with laparotomy. Conclusion: there has been a significant
increase in the laparoscopic route in the treatment of appendicitis, but the
method is still rarely used in SUS patients. The costs of laparoscopic
appendectomy were similar to those observed in laparotomic access.
PMID- 28489206
TI - Lower extremity reconstruction: epidemiology, management and outcomes of patients
of the Federal District North Wing Regional Hospital.
AB - Objective: to evaluate the management of lower limbs complex traumatic injuries
by analyzing their characteristics, types, conduct and evolution, with emphasis
on surgical treatment. Methods: we conducted a prospective study of patients
treated by Plastic Surgery at a regional hospital of the Federal District during
a one-year period. We collected data through serial evaluations and telephone
contact records. Results: we studied 40 patients, with a mean age of 25.6 years,
predominantly male (62.5%). The most frequent wounds were of the distal third of
the lower limb (37.5%). Bone or tendon exposures occurred in 55% had and there
was a 35% rate of exposed lower limb fractures. The treatments employed were skin
grafting (57.5%), local fasciocutaneous flap (15%), muscle flap (12.5%), cross
leg fasciocutaneous flap, reverse sural flap (12.5%) and microsurgical flap
(2.5%). Short-term evaluation showed that 35 patients had excellent or good
results (87.5%), four had a regular result (10%), and one had an unsatisfactory
result (2.5%). In the long term, of the 18 patients who answered the
questionnaire, ten resumed walking, even with support, in the first three months
after surgery (55.6%). Conclusion: young men involved in motorcycle accidents
during leisure time represented the profile of patients with lower limb trauma
requiring surgical reconstruction; the distal third of the leg was the most
affected region. Grafting was the most used technique for reconstruction and
postoperative functional evaluation showed that, despite complex lesions, most
patients evolved with a favorable healing process and successful functional
evolution.
PMID- 28489207
TI - Conversion of Plastic Surgery meeting abstract presentations to full manuscripts:
a brazilian perspective.
AB - Objective: to assess the conversion rate of Plastic Surgery meeting abstract
presentations to full manuscript publications and examine factors associated with
this conversion. Methods: we assessed the abstracts presented at the 47th and
48th Brazilian Congresses of Plastic Surgery by cross-referencing with multiple
databases. We analyzed the Abstracts' characteristics associated with full
manuscript publications. Results: of the 200 abstracts presented, 50 abstracts
were subsequently published in full, giving the conference a conversion rate of
25%. The mean time to publish was 15.00+/-13.75 months. In total, there were
4.93+/-1.63 authors per abstract and 67.8+/-163 subjects per abstract; 43.5% of
the abstracts were of retrospective studies; 69% comprised the plastic surgery
topics head and neck, and chest and trunk, and 88.5% had no statistical analysis.
Overall, 80% of the manuscripts were published in plastic surgery journals, 76%
had no impact factor and 52% had no citations. Bivariate and multivariate
analyses revealed the presence of statistical analysis to be the most significant
(p<0.05) predictive factor of conversion of abstracts into full manuscripts.
Conclusion: the conversion rate found from this bibliometric research appeared a
bit lower than the conversion trend of international plastic surgery meetings,
and statistical analysis was a determinant of conversion success.
PMID- 28489208
TI - Profile of thoracic trauma victims submitted to chest drainage.
AB - Objective: to describe and compare the variables involved in trauma victims
undergoing thoracic drainage. Methods: we conducted a retrospective, analytical,
descriptive, cross-sectional study, with medical records of patients attended at
the Trauma Service of the Curitiba Evangelical University Hospital between
February 2011 and January 2014. Results: there were 488 patients undergoing chest
drainage, 84.7% men and 15.3% women, with an average age of 38.2 years.
Attendances usually occurred at night, without predominance between open or
closed mechanism, gender or age group. The majority of patients with thoracic
trauma requiring drainage were diagnosed by anamnesis and physical examination
(41.1%) and drained in the emergency room (80.8%). Most of the patients (66.2%)
had another associated lesion, mostly some abdominal viscera. Complications were
present in 16.6% (81 patients), most of them due to drainage positioning error
(9.2%). The mean hospital stay was 15 days and drainage lasted for an average of
8.1 days, with no statistical difference between open and closed trauma. The
clinical outcome was discharge in most cases. Conclusion: the profile of patients
with thoracic trauma is that of young men, attended at night, with some other
associated lesion. Although diagnosis and treatment were rapid and most often
without the need for complex examinations, the time of drainage, hospitalization
and complications were higher than in the literature, which can be explained by
the drainage being made at the Emergency Room and the presence of associated
injuries.
PMID- 28489209
TI - Bone grafting for alveolar ridge reconstruction. Review of 166 cases.
AB - Objective: : to investigate the predictive factors of failure in bone grafts for
alveolar ridge augmentation and implant surgery. Methods: : we reviewed the
charts of 166 patients operated between 1995 and 2014. A total of 248 grafting
procedures were performed. We submitted the data to the binomial test at 5%
significance. Results: : grafts to gain width of the alveolar ridge (65.32%) were
more frequent than sinus lifting (p<0.0001) and the number of grafts to the
posterior maxilla (48.8%) was greater than in other regions (p<0.01); 6.04% of
the grafts were lost. The losses in anterior (p<0.0309) and posterior (p<0.0132)
maxilla were higher than in the mandible. There were 269 implants installed in
the grafted areas, of which only 4.83% were lost. The number of implants lost
(4.51%) in areas of onlay grafts was not statistically higher than those placed
after sinus lifting (2.63%, p<0.2424). Losses were greater in the anterior
(53.85%) and posterior (38.46%) maxilla than in the mandible (p<0.031). Regarding
patients' age, 76.92% of the lost grafts (p<0.006) and 80% of the lost implants
(p<0.001) were installed in patients over 40 years. Conclusion: : failure rate
was higher both for grafts and dental implants in the maxilla and in patients
over 40 years of age. Objetivo: : investigar os fatores preditivos de falhas em
enxertos osseos para aumento do rebordo alveolar e cirurgia de implantes.
Metodos: : os prontuarios de 166 pacientes, operados entre 1995 e 2014, foram
revistos. Um total de 248 enxertos foi realizado. Os dados foram submetidos ao
teste binomial a 5% de significancia. Resultados: : os enxertos para ganho em
espessura do rebordo alveolar (65,32%) foram mais frequentes do que levantamentos
de seio maxilar (p<0,0001) e o numero de enxertos para a regiao posterior da
maxila (48,8%) foi maior do que em outras regioes (p<0,01). Foram perdidos 6,04%
dos enxertos. As perdas em maxila anterior (p<0,0132) e posterior (p<0,0309)
foram maiores do que na mandibula. Foram instalados 269 implantes nas areas
enxertadas e apenas 4,83% perdidos. O numero de implantes perdidos (4,51%) em
areas de enxertos em bloco nao foi estatisticamente maior do que na area de seios
maxilares enxertados (2,63%) (p<0,2424). As perdas foram maiores na regiao
anterior (53,85%) e posterior (38,46%) da maxila em relacao a mandibula (p<0,031)
e, 76,92% dos enxertos (p<0,006) e 80% dos implantes perdidos (p<0,001), foram
instalados em pacientes com mais de 40 anos de idade. Conclusao: : maior taxa de
falhas foi observada para enxertos e implantes dentarios realizados em maxila e
em pacientes com mais de 40 anos de idade.
PMID- 28489210
TI - Sugammadex ED90 dose to reverse the rocuronium neuromuscular blockade in obese
patients.
AB - Objective: to determine the ED90 (minimum effective dose in 90% of patients) of
sugammadex for the reversal of rocuronium-induced moderate neuromuscular blockade
(NMB) in patients with grade III obesity undergoing bariatric surgery. Methods:
we conducted a prospective study with the biased coin up-and-down sequential
design. We chosen the following doses: 2.0mg/Kg, 2.2mg/Kg, 2.4mg/Kg, 2.6mg/Kg,
2.8mg/Kg. The complete reversal of rocuronium-induced NMB considered a T4/T1
ratio >=0.9 as measured by TOF. After induction of general anesthesia and
calibration of the peripheral nerve stimulator and accelerometer, we injected
rocuronium 0.6mg/kg. We administered propofol and remifentanil by continuous
infusion, and intermittent boluses of rocuronium throughout the procedure.
Results: we evaluated 31 patients, of whom 26 had displayed successful reversal
of the NMB with sugammadex, and failure in five. The mean time to complete
moderate NMB reversal was 213 seconds (172-300, median 25-75%). The ED90 of
sugammadex calculated by regression was 2.39mg/kg, with a 95% confidence interval
of 2.27-2.46 mg/kg. Conclusion: the ED90 of sugammadex in patients with grade III
obesity or higher was 2.39mg/kg.
PMID- 28489211
TI - Endovascular treatment of carotid-cavernous vascular lesions.
AB - Objective: : to evaluate the endovascular treatment of vascular lesions of the
cavernous segment of the internal carotidartery (ICA) performed at our
institution. Methods: : we conducted a descriptive, retrospective and prospective
study of patients with aneurysms of the cavernous portion of the ICA or with
direct carotid-cavernous fistulas (dCCF) undergoing endovascular treatment.
Results: : we included 26 patients with intracavernous aneurysms and ten with
dCCF. All aneurysms were treated with ICA occlusion. Those with dCCF were treated
with occlusion in seven cases and with selective fistula occlusion in the
remaining three. There was improvement of pain and ocular proptosis in all
patients with dCCF. In patients with intracavernous aneurysms, the incidence of
retro-orbital pain fell from 84.6% to 30.8% after treatment. The endovascular
treatment decreased the dysfunction of affected cranial nerves in both groups,
especially the oculomotor one. Conclusion: : the endovascular treatment
significantly improved the symptoms in the patients studied, especially those
related to pain and oculomotor nerve dysfunction. Objetivo: : avaliar o
tratamento endovascular de lesoes vasculares da arteria carotida interna (ACI),
segmento cavernoso, realizado na Santa Casa de Sao Paulo. Metodos: : estudo
descritivo, retrospectivo e prospectivo, de pacientes com aneurisma da porcao
cavernosa da ACI ou com fistulas carotido-cavernosas diretas (FCCd) submetidos a
tratamento endovascular. Resultados: : foram incluidos 26 pacientes com
aneurismas intracavernosos e dez com FCCd. Todos os aneurismas foram tratados com
oclusao da ACI. Os com FCCd foram tratados com oclusao, em sete casos, e com
oclusao seletiva da fistula nos outros tres. Houve melhora da dor e proptose
ocular em todos os pacientes com FCCd. Nos pacientes com aneurisma
intracavernoso, a incidencia de dor retro-orbitaria caiu de 84,6% para 30,8% apos
o tratamento. Apos o tratamento endovascular houve uma melhora importante da
disfuncao de nervos cranianos afetados em ambos os grupos, sobretudo no nervo
oculomotor. Conclusao: : o tratamento endovascular trouxe melhora para os
pacientes deste estudo, especialmente nos criterios dor e acometimento do nervo
oculomotor.
PMID- 28489212
TI - Impact of using a local protocol in preoperative testing: blind randomized
clinical trial.
AB - Objective: to evaluate the impact of the use of a local protocol of preoperative
test requests in reducing the number of exams requested and in the occurrence of
changes in surgical anesthetic management and perioperative complications.
Methods: we conducted a randomized, blinded clinical trial at the Gaffree and
Guinle University Hospital with 405 patients candidates for elective surgery
randomly divided into two groups, according to the practice of requesting
preoperative exams: a group with non-selectively requested exams and a protocol
group with exams requested according to the study protocol. Studied exams:
complete blood count, coagulogram, glycemia, electrolytes, urea and creatinine,
ECG and chest X-ray. Primary outcomes: changes in surgical anesthetic management
caused by abnormal exams, reduction of the number of exams requested after the
use of the protocol and perioperative complications. Results: there was a
significant difference (p<0.001) in the number of exams with altered results
between the two groups (14.9% vs. 29.1%) and a reduction of 57.3% in the number
of exams requested between the two groups (p<0.001), which was more pronounced in
patients of lower age groups, ASA I, without associated diseases and submitted to
smaller procedures. There was no significant difference in the frequency of
conduct changes motivated by the results of exams or complications between the
two groups. In the multivariate analysis, complete blood count and coagulogram
were the only exams capable of modifying the anesthetic-surgical management.
Conclusion: the proposed protocol was effective in eliminating a significant
number of complementary exams without clinical indication, without an increase in
perioperative morbidity and mortality.
PMID- 28489213
TI - Effects of heparin and hyperbaric oxygenation on necrosis reduction in an animal
model for degloving injuries.
AB - Objective: : to evaluate the efficacy of the treatment with hyperbaric oxygen
therapy or with topical and intralesional heparin in an animal model of degloving
lesions. Methods: : we conducted an experimental study with adult, male Wistar
rats submitted to degloving of the left hind limb and divided into four groups
according to the treatment: Group 1 (control) - without treatment; Group 2
(Heparin) - intralesional application at the time of surgery and topically, in
the postoperative period, with heparin spray 10,000IU/mL; Group 3 (hyperbaric
oxygenation) - daily sessions of 30 minutes in a hyperbaric chamber with 100%
oxygen and 2 ATA pressure; Group 4 (positive control) - administration of a
single dose of 45 mg/kg of intraperitoneal allopurinol. On the seventh day, we
killed the animals, removed the cutaneous flaps and measured the total and
necrotic areas, as well as computed the percentage of necrotic area. Results: :
the mean percentage of necrosis in the control group was 56.03%; in the positive
control group it was 51.36% (p<0.45); in the heparin group, 42.10% (p<0.07); and
in the hyperbaric oxygen therapy group, 31.58% (p<0.01) . Conclusion: : both
hyperbaric oxygen and heparin therapies were effective in reducing the percentage
of necrosis in the model studied, although only the hyperbaric oxygenation showed
statistical significance. Objetivos: : avaliar a eficacia do tratamento com
oxigenoterapia hiperbarica ou com heparina topica e intralesional em modelo
animal de desluvamentos. Metodos: : estudo experimental, com ratos adultos machos
Wistar, submetidos a desluvamento do membro posterior esquerdo e divididos em
quatro grupos, de acordo com o tratamento: Grupo 1 (controle) - sem tratamento;
Grupo 2 (Heparina) - aplicacao intralesional no momento da cirurgia e topica, no
pos operatorio, com spray de heparina 10.000UI/mL; Grupo 3 (oxigenacao
hiperbarica) - sessoes diarias de 30 minutos em camara hiperbarica com 100% de
oxigenio e 2 ATA de pressao; Grupo 4 (controle positivo) - administracao de dose
unica de 45mg/kg de alopurionol intraperitoneal. No setimo dia os animais foram
mortos e os retalhos cutaneos foram retirados e realizadas medidas das areas
total e necrotica, bem como calculo da porcentagem da area de necrose.
Resultados: : a media da porcentagem de necrose do grupo controle foi 56,03%; no
grupo controle positivo, 51,36% (p<=0,45); no grupo da heparina, 42,10% (p<=0,07)
e no grupo da oxigenoterapia hiperbarica, 31,58% (p<=0,01). Conclusao: : tanto a
oxigenoterapia hiperbarica quanto a terapia com heparina mostraram-se eficazes na
reducao do percentual de necrose no modelo estudado, embora neste trabalho apenas
a oxigenacao hiperbarica tenha demonstrado significancia estatistica.
PMID- 28489215
TI - Negative pressure therapy for the treatment of complex wounds.
AB - The objective of this study is to evaluate the effectiveness of negative pressure
therapy (NPT) in the treatment of complex wounds, with emphasis on its mechanisms
of action and main therapeutic indications. We searched the Pubmed / Medline
database for articles published from 1997 to 2016, and selected the most relevant
ones. The mechanisms of action of NPT involveboth physical effects, such as
increased perfusion, control of edema and exudate, reduction of wound dimensions
and bacterial clearance, and biological ones, such as the stimulation of
granulation tissue formation, microdeformations and reduction of Inflammatory
response. The main indications of NPT are complex wounds, such as pressure
ulcers, traumatic wounds, operative wound dehiscences, burns, necrotizing wounds,
venous ulcers, diabetic wounds, skin grafts, open abdomen, prevention of
complications in closed incisions and in the association with instillation of
solutions in infected wounds.
PMID- 28489214
TI - Efficacy of bacterial cellulose membrane for the treatment of lower limbs chronic
varicose ulcers: a randomized and controlled trial.
AB - Objective: to evaluate the efficacy of Bacterial Cellulose (BC) membrane
dressings in the treatment of lower limb venous ulcers. Methods: we carried out a
prospective, randomized, controlled study of 25 patients with chronic venous
ulcer disease in the lower limbs from the Angiology and Vascular Surgery Service
of the Federal University of Pernambuco Hospital and from the Salgado Polyclinic
of the County Health Department, Caruaru, Pernambuco. We randomly assigned
patients to two groups: control group, receiving dressings with triglyceride oil
(11 patients) and experimental group, treated with BC membrane (14 patients). We
followed the patients for a period of 120 days. Results: There was a reduction in
the wound area in both groups. There were no infections or reactions to the
product in any of the groups. Patients in the BC group showed decreased pain and
earlier discontinuation of analgesic use. Conclusion: BC membrane can be used as
a dressing for the treatment of varicose ulcers of the lower limbs.
PMID- 28489216
TI - The role of surgery in the management of women with gestational trophoblastic
disease.
AB - The Gestational Trophoblastic Disease includes an interrelated group of diseases
originating from placental tissue, with distinct behaviors concerning local
invasion and metastasis. The high sensitivity of the serial dosages of human
chorionic gonadotrophin, combined with advances in chemotherapy treatment, have
made gestational trophoblastic neoplasia curable, most often through
chemotherapy. However, surgery remains of major importance in the management of
patients with gestational trophoblastic disease, improving their prognosis.
Surgery is necessary in the control of the disease's complications, such as
hemorrhage, and in cases of resistant/relapsed neoplasia. This review discusses
the indications and the role of surgical interventions in the management of women
with molar pregnancy and gestational trophoblastic neoplasia. RESUMO Doenca
trofoblastica gestacional inclui um grupo interrelacionado de doencas originadas
do tecido placentario, com tendencias distintas de invasao local e metastase. A
alta sensibilidade das dosagens seriadas de gonadotrofina corionica humana aliada
aos avancos do tratamento quimioterapico tornou a neoplasia trofoblastica
gestacional, curavel, na maioria das vezes, atraves da quimioterapia. No entanto,
a cirurgia permanece ainda, da maior importancia na conducao de pacientes com
doenca trofoblastica gestacional, melhorando seu prognostico. A cirurgia e
necessaria no controle de complicacoes da doenca, tais como hemorragia, e em
casos de neoplasia resistente/recidivada. Esta revisao discute as indicacoes e o
papel das intervencoes cirurgicas durante o manejo de mulheres com gravidez molar
e neoplasia trofoblastica gestacional.
PMID- 28489217
TI - Intra-aortic balloon pump in cardiogenic shock: state of the art.
AB - The clinical definition of cardiogenic shock is that of a low cardiac output and
evidence of tissue hypoxia in the presence of adequate blood volume. Cardiogenic
shock is the main cause of death related to acute myocardial infarction (AMI),
with a mortality rate of 45-70% in the absence of aggressive and highly
specialized technical care. The intra-aortic balloon pump (IABP) is one of the
most widely used mechanical assisting devices. During the last two decades, about
42% of patients with AMI who evolved with cardiogenic shock received mechanical
circulatory assistance with IABP. Its clinical indication has been based on non
randomized studies and registry data. Recent studies have shown that the use of
IABP did not reduce 30-day mortality in patients with AMI and cardiogenic shock
treated with the strategy of early myocardial revascularization as the planned
primary objective. The guidelines of the American Heart Association and of the
European Society of Cardiology have reassessed their recommendations based on the
results of meta-analyzes, including the IABP-SCHOCK II Trial study, which did not
evidence an increase in survival of patients who received mechanical support with
IABP. This review article addresses the clinical impact of IABP use in the
cardiogenic shock caused by AMI. RESUMO A definicao clinica de choque
cardiogenico e a de um quadro de baixo debito cardiaco e evidencia de hipoxia
tecidual, na presenca de volemia adequada. O choque cardiogenico representa a
principal causa de obito relacionada ao infarto agudo do miocardio (IAM), com
indice de mortalidade em torno de 45% a 70%, na ausencia de cuidados tecnicos
agressivos e altamente especializados. O balao intra-aortico (BIA) e um dos
dispositivos de assistencia mecanica mais utilizados no mundo. Nas duas ultimas
decadas, cerca de 42% dos pacientes com IAM, que evoluiram com choque
cardiogenico, receberam assistencia circulatoria mecanica com BIA. Sua indicacao
clinica tem sido baseada em estudos nao randomizados e dados de registro. Estudos
recentes tem demonstrado que o uso do BIA nao reduziu a mortalidade hospitalar
(30 dias) em pacientes com IAM e choque cardiogenico, tratados com a estrategia
de revascularizacao precoce do miocardio como objetivo primario planejado. As
diretrizes da Associacao Americana de Cardiologia e da Sociedade Europeia de
Cardiologia reavaliaram suas recomendacoes, baseadas nos resultados de
metanalises, incluindo o estudo IABP-SCHOCK II Trial, que nao evidenciou aumento
na sobrevida de pacientes que receberam suporte mecanico com BIA. Este artigo de
revisao aborda o impacto clinico do uso do BIA no choque cardiogenico ocasionado
pelo IAM.
PMID- 28489218
TI - Percutaneous transbiliary biopsy.
AB - Percutaneous drainage of the bile ducts is an established procedure for malignant
obstructions, in which a histological diagnosis is often not obtained. We
describe the biopsy technique of obstructive lesions through biliary drainage
access, using a 7F endoscopic biopsy forceps, widely available; some are even
reusable. This technique applies to lesions of the hepatic ducts, of the common
hepatic duct and of all extension of the common bile duct. RESUMO A drenagem
percutanea das vias biliares e um procedimento estabelecido para obstrucoes
malignas, nos quais, muitas vezes, nao se consegue um diagnostico histologico.
Descrevemos a tecnica de biopsia da lesao obstrutiva atraves do acesso de
drenagem biliar, utilizando um forcipe de biopsia endoscopica 7F, amplamente
disponivel e alguns reutilizaveis. Esta tecnica aplica-se a lesoes dos ductos
hepaticos, do hepatico comum e de toda extensao do coledoco.
PMID- 28489219
TI - Appraisal of levels and patterns of occupational exposure to 1,3-butadiene.
AB - Objectives 1,3-butadiene is classified as carcinogenic to human by inhalation and
the association with leukemia has been observed in several epidemiological
studies. The aim of this study was to evaluate data about occupational exposure
levels to 1,3-butadiene in the Italian working force. Methods Airborne
concentrations of 1,3-butadiene were extracted from the Italian database on
occupational exposure to carcinogens in the period 1996-2015. Descriptive
statistics were calculated for exposure-related variables. An analysis through
linear mixed model was performed to determine factors influencing the exposure
level. The probability of exceeding the exposure limit was predicted using a
mixed-effects logistic model. Concurrent exposures with other occupational
carcinogens were investigated using the two-step cluster analysis. Results The
total number of exposure measurements selected was 23 885, with an overall
arithmetic mean of 0.12 mg/m3. The economic sector with the highest number of
measurements was manufacturing of chemicals (18 744). The most predictive
variables of the exposure level resulted to be the occupational group and its
interaction with the measurement year. The highest likelihood of exceeding the
exposure limit was found in the manufacture of coke and refined petroleum
products. Concurrent exposures were frequently detected, mainly with benzene,
acrylonitrile and ethylene dichloride, and three main clusters were identified.
Conclusions Exposure to 1,3-butadiene occurs in a wide variety of activity
sectors and occupational groups. The use of several statistical analysis methods
applied to occupational exposure databases can help to identify exposure
situations at high risk for workers' health and better target preventive
interventions and research projects.
PMID- 28489220
TI - Transition from Pediatric to Adult Care Is So Important and Challenging.
PMID- 28489221
TI - Addressing Eating Disorders and Weight Control in Children and Adolescents.
AB - How often do we look at a patient's body mass index (BMI) and only make a comment
if the BMI is above normal in the overweight or obese category? As pediatricians,
we often do not give it a second thought when the BMI is normal, and we generally
do not counsel on healthy eating practices in these cases. However, when people
are overweight, obese, and sometimes even normal weight they are told by family,
friends, as well as physicians that they need to either not gain any more weight,
or that they need to lose weight. As clinicians, we should be aware that comments
like that may trigger a disordered pattern of eating for some people, which can
lead to an eating disorder. [Pediatr Ann. 2017;46(5):176-e179.].
PMID- 28489222
TI - Transition Medicine-From Pediatric to Adult Care: Part 1.
PMID- 28489223
TI - A Review of Interventions Aimed at Facilitating Successful Transition Planning
and Transfer to Adult Care Among Youth with Chronic Illness.
AB - This article reviews studies that developed interventions aimed at facilitating
the transition process and/or the transfer of youth with chronic illness to adult
programs during the past decade. Three key intervention approaches have been
studied. Data assessing the impact of transition coordinators suggest that the
most successful outcomes occur when coordinators meet with patients prior to the
transfer of care, support them as they negotiate the adult programs, and
facilitate appointment keeping. Data assessing the impact of transition clinics
suggest that the key to positive outcomes is helping patients develop a trusting
relationship with the adult providers before fully transferring their care to the
adult clinic. Similar conclusions can be drawn for transition programs, where it
appears that the opportunity to discuss and plan transition with a pediatric
provider over time and to meet with both the pediatric and adult providers
simultaneously are beneficial for facilitating successful transfer to adult care.
Although aspects of these care processes appear promising for improving
transition success, this review identifies areas that need further study. We
argue that studies are needed that examine individual patient and family-focused
interventions as well as looking at other potential interventions in the health
care system. [Pediatr Ann. 2017;46(5):e182-e187.].
PMID- 28489225
TI - Models of Care for Adolescents and Young Adults with Type 1 Diabetes in
Transition: Shared Medical Appointments and Telemedicine.
AB - Transitioning through adolescence and young adulthood is challenging, and even
more so for patients living with a chronic disease such as type 1 diabetes.
Patients in this age group encounter multiple obstacles to effectively managing
their diabetes, experience suboptimal glycemic control, face higher rates of
acute complications, and are often lost to medical follow-up. Comprehensive
strategies and innovative clinical models are needed to engage this population in
diabetes medical care, address barriers to ideal management, and improve
outcomes. Telemedicine, shared medical appointments (SMA), or a combination of
telemedicine and SMA are potential models to more successfully, efficiently, and
satisfactorily address the urgent need for improved care in this high-risk
population. This article reviews various clinical care models within these
categories of telemedicine and SMA. [Pediatr Ann. 2017;46(5):e193-e197.].
PMID- 28489224
TI - Current Concepts of Transition of Care in Cystic Fibrosis.
AB - Over the past 6 decades, advances in cystic fibrosis (CF) diagnosis and
management have extended the life expectancy of patients far beyond childhood;
therefore, all pediatric CF patients must prepare for transition to adult care.
Readiness assessment, knowledge and skill education, and support structures are
all elements of ideal transition. Transition should begin early in life with
teaching skills and knowledge for disease care, and in adolescence the readiness
to transition should be addressed. Transition is a gradual process of increasing
responsibilities in self-care and disease management, an improvement in the
understanding of CF, and an iterative process of self-assessment with knowledge
acquisition. Communication and collaboration between pediatric and adult
providers is necessary to ensure a smooth and successful transition with minimum
effect on outcomes. Although there is increased knowledge of successful
transition practices, this area presents many opportunities for advancement of
care for the patient with CF. [Pediatr Ann. 2017;46(5):e188-e192.].
PMID- 28489226
TI - Transition of Care for Youth with HIV.
AB - Remarkable advances have been made in the treatment of HIV. Despite progress in
reducing perinatal HIV transmission, there is a growing number of adolescents and
emerging adults with HIV who will require transfer of care from pediatric to
adult providers. Adolescents with HIV have poorer retention in care and viral
suppression compared to other age groups with HIV. Barriers to successful care of
youth with HIV include mental health disorders, poor medication adherence,
socioeconomic instability, and HIV-related stigma. Transfer of care to adult
providers is often met with reluctance on the part of the adolescent.
Recommendations for effective transfer of care include clear communication
between adult and pediatric providers, early initiation of a transition planning
discussion, a multidisciplinary team approach, and meeting the adult provider
prior to the transfer of care. Adult HIV care may be more fragmented than
adolescents are familiar with, but thoughtful transition approaches can foster
development of health and life skills among youth with HIV. [Pediatr Ann.
2017;46(5):e198-e202.].
PMID- 28489227
TI - Using Quality Improvement in Resident Education to Improve Transition Care.
AB - The importance of a specific transition process is recognized by many health
organizations. Got Transition, a cooperative endeavor aimed at improving the
transition from pediatric to adult health care, developed Six Core Elements
defining the basic components of health care transition support. In this article,
we review the Six Core Elements by presenting a model that combines resident
quality improvement and transition care training. In this Internal Medicine
Pediatrics residency program, ambulatory training for residents takes place in a
combined adult and pediatric clinic. Aligned with the Six Core Elements, the
program has crafted and disseminated a transition policy for the practice,
designed a portable health summary template for the electronic medical record
(EMR), created EMR tools for assessing transition readiness and setting
transition goals, formed a registry of patients, and audited charts. [Pediatr
Ann. 2017;46(5):e203-e206.].
PMID- 28489228
TI - An Update on Pediatric Pancreatitis.
AB - There has been a rise in the incidence and number of admissions of children with
pancreatitis over the past 20 years. Current management practices for
pancreatitis in children are adapted from standards of care for adults, and there
are a lack of multicenter, prospective research studies on pancreatitis in
children. There are inherent differences in the clinical presentation and natural
course of pancreatitis between adults and children. This review focuses on the
current understanding of the epidemiology, etiologies, evaluation, and management
of children with pancreatitis. [Pediatr Ann. 2017;46(5):e207-e211.].
PMID- 28489229
TI - Regent: An invaluable new offering from the American Academy of Otolaryngology
Head and Neck Surgery.
PMID- 28489230
TI - Facial nerve mimicking the fibrocartilaginous annulus of the tympanic membrane.
PMID- 28489231
TI - A huge parapharyngeal space tumor in a child.
PMID- 28489232
TI - Elastofibroma.
PMID- 28489233
TI - Linear IgA dermatosis limited to the mucosal membranes as a rare cause of
dysphagia.
PMID- 28489234
TI - The treatment of otorrhea in children with cleft palate: An institutional review.
AB - We conducted a retrospective observational chart review to characterize otorrhea
in patients with cleft palate (CP) after tympanostomy tube placement in terms of
the bacteria profile, treatment effectiveness, and overall disease burden. A
total of 157 patients over 6 years were reviewed. Fifty of the 157 patients
(31.8%) experienced postoperative otorrhea. Of the 50 patients with otorrhea, all
received topical antibiotics, 30 received oral antibiotics, and 12 received
povidone-iodine irrigations. The average duration of otorrhea was 5.2 months for
patients with povidone-iodine irrigations and 8.5 months for those without
povidone-iodine irrigations. Methicillin-resistant Staphylococcus aureus was the
most commonly cultured microorganism. The average number of total healthcare
visits over a 12-month period was 13.6 per patient. We conclude that
postoperative otorrhea is a common problem after tympanostomy tube placement in
children with CP and places a significant burden on these patients and the
healthcare system. The bacteriologic profile may be different in this population
compared with the non-CP population with otorrhea after tympanostomy, and a
search for more effective treatment options is warranted, including further
investigation into povidone-iodine irrigations.
PMID- 28489235
TI - Long-term follow-up of KTP laser turbinate reduction for the treatment of
obstructive rhinopathy.
AB - We investigated the subjective, long-term, patient-reported symptom control after
endoscopic potassium titanyl phosphate (KTP) laser reduction of the inferior
turbinates. Symptoms were listed preoperatively and patients were asked, via
telephone interview, the status of their symptoms. Chi-square analysis was used
to assess statistical significance of the surgical intervention. Thirty-six
patients (male:female ratio: 5:4) aged 13 to 80 years (mean: 37.2) were available
for follow-up. The mean follow-up time was 68.47 months (range: 44 to 92). The
principal symptom patients experienced was nasal obstruction (94.4%);
postoperative improvement in this symptom at 44 months and beyond was reported by
85.3% of patients (chi-square 16.94, p < 0.001). Other symptoms, such as
rhinorrhea and sneezing, showed no significant improvement at long-term follow
up. This study adds evidence to the long-term improvements in obstructive nasal
symptoms using KTP laser reduction of the turbinates.
PMID- 28489236
TI - Histologic correlation of VEGF and COX-2 expression with tumor size in squamous
cell carcinoma of the larynx and hypopharynx.
AB - The prognosis and survival of patients with laryngeal and hypopharyngeal squamous
cell carcinoma (SCC) are related to the clinical staging. Tumor growth and
metastasis are closely related to angiogenesis. Vascular endothelial growth
factor (VEGF) and cyclooxygenase 2 (COX-2) are intimately related to the
angiogenic process in which the blood supply required for neoplastic evolution is
ensured. Considering the contributions of VEGF and COX-2 to the formation,
growth, and progression of primary tumors, as well as their metastasis, it has
been thought that the expression of these two factors might be related to the
size and/or aggressiveness of laryngeal and hypopharyngeal cancer. To test that
theory, we conducted a retrospective study to evaluate the expression of VEGF and
COX-2 markers in archived specimens of SCC of the larynx and hypopharynx to
correlate their expression with tumor size. These specimens had been obtained
from 35 patients-31 men and 4 women, aged 37 to 75 years (mean: 57)-who had been
treated for laryngeal or hypopharyngeal SCC at our tertiary care university
hospital over a period of 15 years. Immunohistochemical analyses were performed
with avidin-biotin-peroxidase staining for VEGF and COX-2 antibodies. The degree
of VEGF and COX-2 expression was based on the German scale of immunoreactivity.
Specimens were separated into groups based on the intensity of expression
(none/low and moderate/strong) and tumor size (TNM categories T1/T2 and T3/T4). A
total of 7 patients exhibited moderate or strong VEGF expression (3 from the
T1/T2 group and 4 from the T3/T4 group), and 17 patients demonstrated moderate or
strong COX-2 expression (8 from the T1/T2 group and 9 from the T3/T4 group). We
found no statistically significant relationship between tumor size and either
VEGF or COX-2 expression. Our study demonstrated that despite the intrinsic
connection between and VEGF and COX-2, neither appears to be related to the size
of the SCCs of the larynx or hypopharynx. Other factors must be involved in the
pathogenesis and progression of this disease, and further studies are needed to
identify them.
PMID- 28489237
TI - Medially displaced common and internal carotid arteries presenting as a pulsatile
mass: Clinicoradiologic analysis of 62 cases.
AB - We conducted a prospective study to analyze the medially displaced courses of the
common carotid artery (CCA) and the cervical segment of the internal carotid
artery (ICA) in patients who were diagnosed with a pulsatile mass on
nasopharyngolaryngoscopy and by clinicoradiologic findings. Our study group was
made up of 62 patients-40 women and 22 men, aged 30 to 88 years (mean: 63.7)-who
presented with a submucosal pseudomass or a bulging mass on the pharyngeal wall
with obvious pulsation. For comparison purposes, we recruited a control group of
62 consecutively presenting patients who had been admitted to our Neurology
Department with acute severe headache and who had undergone CT angiography based
on a suspicion of an aneurysm or a vertebral or carotid artery dissection. A
medially displaced carotid artery was identified in all patients in the study
group. Two main course abnormalities were observed: (1) a pharyngeal superficial
placement (PSP), consisting of a bulging or placement immediately adjacent to the
naso-orohypopharyngeal lumen, and (2) a retropharyngeal midline placement (RMP),
which entailed medialization of the carotid arteries to the midline. A PSP was
observed in 11 patients, an RMP was found in 17 patients, and both were seen in
34 patients. The distance from the aberrant carotid artery to the pharyngeal wall
and to the retropharyngeal midline of the retropharynx was measured at four
levels: nasopharyngeal, retropalatal, retroglossal, and retroepiglottic in both
groups. The mean distance was significantly shorter in the study group than in
the control group at all four levels (p < 0.002). We conclude that the most
likely diagnosis of a pulsatile mass detected on nasopharyngolaryngoscopy is an
aberrant CCA or cervical ICA.
PMID- 28489238
TI - Quality-of-life outcomes in Graves disease patients after total thyroidectomy.
AB - Historically, research into surgical treatment of Graves disease has assessed
subtotal rather than total thyroidectomy. Most clinicians now recommend total
thyroidectomy, but little information is available regarding quality-of-life
(QOL) outcomes for this procedure. Our aim was to assess QOL after total
thyroidectomy. This is a retrospective, pilot study of patients with Graves
disease who underwent total thyroidectomy from 1991 to 2007 at a high-volume
tertiary referral center in Toronto, Canada. Questionnaires addressing disease
specific symptoms and global QOL concerns were sent to 54 patients. Analyses
included parametric and nonparametric tests to assess the differences between
perception of symptoms and global QOL before and after surgery. Forty patients
responded (response rate: 74%) at a median of 4.8 years postoperatively. On a 10
point scale, overall wellness improved from 4.1 preoperatively to 8.7
postoperatively (p < 0.001). Patients recalled missing less work or school after
surgery (7.8 vs. 1.1 days/year; p = 0.001). Overall satisfaction with the
procedure was high. On average, symptoms improved within 32 days of surgery, and
all symptoms showed substantial improvement. This is the first North American
study to assess QOL outcomes of patients with Graves disease after total
thyroidectomy. Patients experienced marked and rapid improvement in QOL
postoperatively. These findings suggest that total thyroidectomy is a safe and
effective treatment.
PMID- 28489239
TI - Therapeutic effect of hyaluronic acid in reducing nasal mucosa recovery time
after septoplasty.
AB - Mucociliary clearance represents a host defense mechanism of airways that can be
compromised by various pathologic conditions, such as nasal septal deviation.
Although septoplasty can resolve obstruction, it impairs mucociliary clearance in
the immediate postoperative period. Clinical studies have demonstrated how
hyaluronic acid can interfere with this function. Our study aims to provide
evidence of a therapeutic effect of hyaluronic acid on nasal mucosa recovery
after septoplasy. Sixty-five patients underwent septoplasty. On postoperative day
1, patients were randomized to a control arm that was treated with mupirocin
ointment or an experimental arm that received additional treatment with sodium
hyaluronate solution. Pre- and postoperatively, anterior rhinoscopy was performed
to analyze mucosal status, and mucociliary clearance was measured by using the
saccharin transit time (STT) method. The t test was used for independent groups.
During the preoperative evaluation, we observed a significant difference in STT
between the convex and concave side in both groups. Fifteen days after surgery,
we observed a significant difference preoperatively to postoperatively for both
the convex and the concave side (p < 0.02 and p < 0.008, respectively). One month
after surgery, we observed a reduction of STT when comparing preoperative control
group values and, after 1 month, postoperative values in both sides (p < 0.015
and p < 0.005, convex and concave side, respectively). Our results show a
significant reduction of the STT for both nasal sides as soon as 15 days after
septoplasty in patients randomized to additional treatment. Our experience
provides further evidence for the therapeutic effect of hyaluronic acid in
accelerating nasal mucosa recovery after septoplasty.
PMID- 28489240
TI - The role of hypertonic saline in monopolar tonsillectomy in adult patients.
AB - This study's objective was to look for a simple and inexpensive method to reduce
patients' pain during tonsillectomy. Bilateral tonsillectomy patients were
enrolled and placed into different groups based on their admission numbers.
Patients with odd numbers had electrical tonsillectomy on the right side with
hypertonic saline injection into the tonsillar capsule (group A) or electrical
tonsillectomy on the left side with normal saline injection (group B). Those with
even numbers had electrical tonsillectomy on the left side with hypertonic saline
injection into the tonsillar capsule (group A) or electrical tonsillectomy on the
right side with normal saline injection (group B). Pain, operative bleeding,
postoperative bleeding, and operation time were evaluated. Injecting hypertonic
saline into the tonsillar capsule reduced pain caused by electrical tonsillectomy
but did not impact the operative or postoperative bleeding and operation time.
While simple and economic, monopolar electrical tonsillectomy with the help of
hypertonic saline injected into the tonsillar capsule can effectively relieve
patients' pain when compared to surgeries with normal saline injection.
PMID- 28489241
TI - In-office vs. operating room procedures for recurrent respiratory papillomatosis.
AB - We conducted a study to analyze hospital and patient costs, outcomes, and patient
satisfaction among adults undergoing in-office and operating room procedures for
the treatment of recurrent respiratory papillomatosis. Our final study population
was made up of 17 patients-1 man and 16 women, aged 30 to 86 years (mean: 62).
The mean number of in-office laser procedures per patient was 4.2, and the mean
interval between procedures was 5.4 months (although 10 patients underwent only 1
office procedure); the mean number of operating room procedures was 13.5, and the
mean interval between procedures was 14.3 months. An equal number of patients
reported complications or adverse events with the two types of procedures-5 each.
The difference in cost between the office procedure (mean: $3,413.00) and the
operating room procedure (mean: $12,382.59) was almost $9,000, but these savings
were offset by the fact that the office procedures needed to be performed three
times as often. Patients reported slightly more anxiety and discomfort during the
office procedures and, overall, they appeared to prefer the operating room
procedure. We conclude that office procedures are significantly more cost
effective than operating room procedures, but their use may be limited by patient
tolerance and the increased frequency of the procedure.
PMID- 28489242
TI - Large pediatric maxillary dentigerous cysts presenting with sinonasal and orbital
symptoms: A case series.
AB - Dentigerous cysts are benign odontogenic cysts associated with the crowns of
unerupted, embedded, or impacted teeth. Most of them are associated with
mandibular third molars, followed by maxillary third molars and canines. They are
usually asymptomatic, and rarely do they grow extensively and compress the
adjacent anatomic structures. We report 5 cases of extensive maxillary
dentigerous cysts presenting with sinonasal and orbital symptoms. A literature
review for similar presentations of dentigerous cysts has demonstrated 21 cases.
Recognition of the extensive growth potential of the dentigerous cyst, diagnosing
it with its unusual presentation, and appropriate management are discussed in
this article.
PMID- 28489243
TI - Nasal, pharyngeal, and laryngeal pemphigus vulgaris successfully treated with
rituximab.
AB - Pemphigus vulgaris is a potentially fatal autoimmune blistering disease that can
involve the nasopharyngeal and laryngeal tissues. The disease can be recalcitrant
to conventional oral treatments, and treatment alternatives are limited. This
retrospective study evaluated the efficacy of rituximab as a rescue agent in 5
patients with recalcitrant pemphigus vulgaris involving nasopharyngeal and
laryngeal mucosa. All 5 patients were unresponsive to systemic steroids and at
least one conventional oral immunosuppressive agent. The patients received
rituximab infusions as a rescue agent because of recalcitrant disease. All 5
patients had a complete clinical response to rituximab and could discontinue
systemic steroids and reduce the dosage of their initial immunosuppressive agent.
No major adverse reactions were observed or reported with rituximab. Rituximab
can be used as an effective rescue agent in the treatment of severe pemphigus
vulgaris with nasopharyngeal and laryngeal involvement.
PMID- 28489244
TI - Role of intraoperative ropivacaine in adult post-tonsillectomy pain control: A
randomized controlled trial.
AB - We sought to evaluate the efficacy of ropivacaine in post-tonsillectomy pain
management in adults and evaluate the timing of intraoperative ropivacaine
administration for this purpose. A prospective, double-blinded, randomized,
controlled trial with a paired design was performed in 25 consecutive adults
undergoing tonsillectomy. To date, no studies examining the efficacy of local
anesthetics in post-tonsillectomy pain control have used a paired design to
account for the variability in pain difference between individuals. Patients were
prerandomized into those receiving tonsillar fossa injections before or after the
tonsillectomy. All surgeries were performed by the senior author. The tonsil on 1
side was injected with saline and the tonsil on the other side with ropivacaine.
Patient responses were obtained via written questionnaire. Three of 25 patients
were excluded from the study. Sixteen of 22 patients had lateralization of pain
to 1 side during recovery. No statistically significant difference in pain
control was observed between ropivacaine and normal saline. Local anesthetic
decreased pain in 7 of 22 patients, and increased pain was experienced on the
side with local anesthetic in 9 of 22 patients. Six of 22 patients had no
difference in pain from one side to the other. The time to equalization of pain
based on laterality was 8.8 and 6.8 days, respectively, in the patients injected
before or immediately after the tonsillectomy. Administration of the local
anesthetic ropivacaine does not affect post-tonsillectomy pain. Moreover, timing
of injection does not affect postoperative pain. We recommend against the use of
intraoperative ropivacaine for pain control in patients undergoing tonsillectomy.
PMID- 28489245
TI - Stapes-pyramidal fixation by a bony bar [Letter].
PMID- 28489246
TI - Atypical presentation of vocal fold granulomas.
PMID- 28489247
TI - Endoscopic view of long-term patency of the sphenoid ostium following balloon
dilation.
PMID- 28489248
TI - Intact FGF23 and alpha-klotho during acute inflammation/sepsis in CKD patients.
PMID- 28489249
TI - Validation of two prognostic models for recurrence and survival after radical
gastrectomy for gastric cancer.
AB - BACKGROUND: Prognostic models from Korea and Italy have been developed that
predict overall survival and cancer recurrence respectively after radical
gastrectomy for gastric cancer. The aim of this study was to validate the two
models in independent patient cohorts, and to evaluate which factors may explain
differences in prognosis between Korean and Italian patients with gastric cancer.
METHODS: Patients who underwent radical gastrectomy for gastric cancer between
January 2000 and December 2004 at Seoul National University Hospital and at eight
centres in Italy were included. Discrimination of the models was tested with
receiver operating characteristic (ROC) curves and calculation of area under the
curve (AUC). Calibration was evaluated by plotting actual survival probability
against predicted survival probability for the Korean nomogram, and actual
against predicted risk of recurrence for the Italian score. RESULTS: Some 2867
and 940 patients from Korea and Italy respectively were included. The Korean
nomogram achieved good discrimination in the Italian cohort (AUC 0.80, 95 per
cent c.i. 0.77 to 0.83), and the Italian model performed well in the Korean
cohort (AUC 0.87, 0.85 to 0.89). The Korean nomogram also achieved good
calibration, but this was not seen for the Italian model. Multivariable analyses
confirmed that Italian ethnicity was an independent risk factor for cancer
recurrence (odds ratio (OR) 1.72, 1.31 to 2.25; P < 0.001), but not for overall
survival (OR 1.20, 0.95 to 1.53; P = 0.130). CONCLUSION: Both prognostic models
performed fairly well in independent patient cohorts. Differences in recurrence
rates of gastric cancer may be partially explained by ethnicity.
PMID- 28489251
TI - Geographically structured genetic variation in the Medicago lupulina-Ensifer
mutualism.
AB - Gene flow between genetically differentiated populations can maintain variation
in species interactions, especially when population structure is congruent
between interacting species. However, large-scale empirical comparisons of the
population structure of interacting species are rare, particularly in positive
interspecific interactions (mutualisms). One agriculturally and ecologically
important mutualism is the partnership between legume plants and rhizobia.
Through characterizing and comparing the population genomic structure of the
legume Medicago lupulina and two rhizobial species (Ensifer medicae and E.
meliloti), we explored the spatial scale of population differentiation between
interacting partners in their introduced range in North America. We found high
proportions of E. meliloti in southeastern populations and high proportions of E.
medicae in northwestern populations. Medicago lupulina and the Ensifer genus
showed similar patterns of spatial genetic structure (isolation by distance).
However, we detected no evidence of isolation by distance or population structure
within either species of bacteria. Genome-wide nucleotide diversity within each
of the two Ensifer species was low, suggesting limited introduction of strains,
founder events, or severe bottlenecks. Our results suggest that there is
potential for geographically structured coevolution between M. lupulina and the
Ensifer genus, but not between M. lupulina and either Ensifer species.
PMID- 28489250
TI - Causal mechanisms of soil organic matter decomposition: deconstructing salinity
and flooding impacts in coastal wetlands.
AB - Coastal wetlands significantly contribute to global carbon storage potential. Sea
level rise and other climate-change-induced disturbances threaten coastal wetland
sustainability and carbon storage capacity. It is critical that we understand the
mechanisms controlling wetland carbon loss so that we can predict and manage
these resources in anticipation of climate change. However, our current
understanding of the mechanisms that control soil organic matter decomposition,
in particular the impacts of elevated salinity, are limited, and literature
reports are contradictory. In an attempt to improve our understanding of these
complex processes, we measured root and rhizome decomposition and developed a
causal model to identify and quantify the mechanisms that influence soil organic
matter decomposition in coastal wetlands that are impacted by sea-level rise. We
identified three causal pathways: (1) a direct pathway representing the effects
of flooding on soil moisture, (2) a direct pathway representing the effects of
salinity on decomposer microbial communities and soil biogeochemistry, and (3) an
indirect pathway representing the effects of salinity on litter quality through
changes in plant community composition over time. We used this model to test the
effects of alternate scenarios on the response of tidal freshwater forested
wetlands and oligohaline marshes to short- and long-term climate-induced
disturbances of flooding and salinity. In tidal freshwater forested wetlands, the
model predicted less decomposition in response to drought, hurricane salinity
pulsing, and long-term sea-level rise. In contrast, in the oligohaline marsh, the
model predicted no change in response to drought and sea-level rise, and
increased decomposition following a hurricane salinity pulse. Our results show
that it is critical to consider the temporal scale of disturbance and the
magnitude of exposure when assessing the effects of salinity intrusion on carbon
mineralization in coastal wetlands. Here, we identify three causal mechanisms
that can reconcile disparities between long-term and short-term salinity impacts
on organic matter decomposition.
PMID- 28489252
TI - Social effects for locomotion vary between environments in Drosophila
melanogaster females.
AB - Despite strong purifying or directional selection, variation is ubiquitous in
populations. One mechanism for the maintenance of variation is indirect genetic
effects (IGEs), as the fitness of a given genotype will depend somewhat on the
genes of its social partners. IGEs describe the effect of genes in social
partners on the expression of the phenotype of a focal individual. Here, we ask
what effect IGEs, and variation in IGEs between abiotic environments, has on
locomotion in Drosophila. This trait is known to be subject to intralocus
sexually antagonistic selection. We estimate the coefficient of interaction, Psi,
using six inbred lines of Drosophila. We found that Psi varied between abiotic
environments, and that it may vary across among male genotypes in an abiotic
environment specific manner. We also found evidence that social effects of males
alter the value of a sexually dimorphic trait in females, highlighting an
interesting avenue for future research into sexual antagonism. We conclude that
IGEs are an important component of social and sexual interactions and that they
vary between individuals and abiotic environments in complex ways, with the
potential to promote the maintenance of phenotypic variation.
PMID- 28489253
TI - Randomized clinical trial comparing collagen plug and advancement flap for trans
sphincteric anal fistula.
AB - BACKGROUND: The role of a collagen plug for treating anal fistula is not well
established. A randomized prospective multicentre non-inferiority study of
surgical treatment of trans-sphincteric cryptogenic fistulas was undertaken,
comparing the anal fistula plug with the mucosal advancement flap with regard to
fistula recurrence rate and functional outcome. METHODS: Patients with an anal
fistula were evaluated for eligibility in three centres, and randomized to either
mucosal advancement flap surgery or collagen plug, with clinical follow-up at 3
and 12 months. The primary outcome was the fistula recurrence rate. Anal pain
(visual analogue scale), anal incontinence (St Mark's score) and quality of life
(Short Form 36 questionnaire) were also reported. RESULTS: Ninety-four patients
were included; 48 were allocated to the plug procedure and 46 to advancement flap
surgery. The median follow-up was 12 (range 9-24) months. The recurrence rate at
12 months was 66 per cent (27 of 41 patients) in the plug group and 38 per cent
(15 of 40) in the flap group (P = 0.006). Anal pain was reduced after operation
in both groups. Anal incontinence did not change in the follow-up period.
Patients reported an increased quality of life after 3 months. There were no
differences between the groups with regard to pain, incontinence or quality of
life. CONCLUSION: There was a considerably higher recurrence rate after the anal
fistula plug procedure than following advancement flap repair. Registration
number: NCT01021774 (http://www.clinicaltrials.gov).
PMID- 28489254
TI - Use of intra-aortic counterpulsation in cardiogenic shock post-liver
transplantation.
AB - Left ventricular dysfunction resulting in cardiogenic shock occurs infrequently
following organ reperfusion in liver transplantation. The etiology of the
cardiogenic shock is often multifactorial and difficult to manage due to the
complex nature of the procedure and the patient's baseline physiology.
Traditionally, this hemodynamic instability is managed medically using inotropic
agents and vasopressor support. If medical treatment is insufficient, the use of
an intra-aortic balloon pump for counterpulsation may be employed to improve the
hemodynamics and stabilize the patient. Here, we analyze three cases and review
the literature.
PMID- 28489255
TI - Increased risk of portal vein thrombosis in patients with autoimmune hepatitis on
the liver transplantation waiting list.
AB - Liver transplantation (LT) is indicated in autoimmune hepatitis (AIH) for both
acute presentation with liver failure and end-stage chronic liver disease. Few
studies have suggested an association between AIH and coagulation disorders and a
higher incidence of portal vein thrombosis (PVT) in patients with AIH listed for
LT. The aim of this study was to determine the incidence of thrombotic
complications, particularly PVT, in a cohort of 37 patients undergoing LT because
of AIH. PVT was present before transplantation in 30% (n=11) of these patients
compared to 11% in the whole population transplanted in our center (P=.002). On
comparing only patients with cirrhosis, PVT was present in 55% of the AIH group,
being 12% in the whole cohort (P<.001). Among patients with PVT before LT, no
patient receiving anticoagulation therapy early after LT developed recurrence of
PVT, whereas two patients (33%) without anticoagulation therapy did. The
increased incidence of PVT in the pretransplant period and the possibility of
thrombosis recurrence after LT suggest that patients with AIH and PVT could
benefit from anticoagulation therapy after transplantation. However, further
studies are needed to recommend anticoagulation in these patients in clinical
practice.
PMID- 28489256
TI - Clinical and virologic outcomes in high-risk adult Epstein-Barr virus mismatched
organ transplant recipients.
AB - Epstein-Barr virus (EBV) D+/R- organ transplant recipients are a high-risk group
for developing post-transplant lymphoproliferative disease (PTLD). Little data
are available for prevention in the adult EBV mismatched population. We conducted
a retrospective study of EBV D+/R- organ transplants performed during 2002-2014.
Of the 153 patients identified, 82.4% patients received antiviral prophylaxis
with valganciclovir for a median of 4.5 months (range: 0.8-22 months) and 36.6%
underwent viral load monitoring in the first post-transplant year. EBV viremia
developed in 67.2% monitored patients. In viremic patients, immunosuppression was
reduced in 20/37(54.1%) in response to viremia and 17/37 (45.9%) received
therapeutic dose valganciclovir. In patients with EBV viremia who received
valganciclovir and/or had a reduction in immunosuppression and had sufficient
viral load time points (n=31), 28 (90.3%) had a significant decline in viral load
at day 14 (median log decline 0.49 (0.24-0.64), P<.001) and at day 30 (0.87 (0.52
1.21), P<.001). PTLD developed in 27 (15%) patients (biopsy proven=25,
possible=2) at median 8 months (range: 2.4-130) post-transplant with the majority
(81.5%) within the first year. In multivariate analysis, viral load monitoring
and use of mycophenolate were associated with a lower incidence of PTLD.
Antiviral prophylaxis was not associated with a lower risk of PTLD, but viral
load monitoring and use of mycophenolate mofetil were protective.
PMID- 28489258
TI - Triggered and Tunable Hydrogen Sulfide Release from Photogenerated
Thiobenzaldehydes.
AB - Hydrogen sulfide (H2 S) has been identified as an important cell-signaling
mediator and has a number of biological functions, such as vascular smooth muscle
relaxation, neurotransmission, and regulation of inflammation. A facile and
versatile approach for H2 S production initiated by light irradiation and
controlled by reaction with an amine or an amino acid was developed. The donor
was synthesized in a one-pot reaction, and simple crystallization led to a yield
of approximately 90 %. The synthetic strategy is scalable and versatile, and the
H2 S donors can be expressed ina number of different molecular and macromolecular
forms, including crystalline small-molecule compounds, water-soluble polymers,
polystyrene films, and hydrogels. The H2 S donors based on polystyrene film and
hydrogel were used as cell-culture scaffolds. The H2 S donor based on water
soluble polymer was applied in photocontrolled inhibition of P-selectin
expression on human platelets and subsequent regulation of platelet aggregation.
This study provides the simplest controllable H2 S source to study its biological
functions. The developed materials are also new therapeutic platforms to deliver
H2 S, as there is no accumulation of toxic byproducts, and the donor materials
from polystyrene films and hydrogels can be readily removed after releasing H2 S.
PMID- 28489257
TI - Unsaturated Long-Chain Fatty Acids Are Preferred Ferritin Ligands That Enhance
Iron Biomineralization.
AB - Ferritin is a ubiquitous nanocage protein, which can accommodate up to thousands
of iron atoms inside its cavity. Aside from its iron storage function, a new role
as a fatty acid binder has been proposed for this protein. The interaction of apo
horse spleen ferritin (HoSF) with a variety of lipids has been here investigated
through NMR spectroscopic ligand-based experiments, to provide new insights into
the mechanism of ferritin-lipid interactions, and the link with iron
mineralization. 1D 1 H, diffusion (DOSY) and saturation-transfer difference (STD)
NMR experiments provided evidence for a stronger interaction of ferritin with
unsaturated fatty acids compared to saturated fatty acids, detergents, and bile
acids. Mineralization assays showed that oleate c aused the most efficient
increase in the initial rate of iron oxidation, and the highest formation of
ferric species in HoSF. The comprehension of the factors inducing a faster
biomineralization is an issue of the utmost importance, given the association of
ferritin levels with metabolic syndromes, such as insulin resistance and
diabetes, characterized by fatty acid concentration dysregulation. The human
ferritin H-chain homopolymer (HuHF), featuring ferroxidase activity, was also
tested for its fatty acid binding capabilities. Assays show that oleate can bind
with high affinity to HuHF, without altering the reaction rates at the
ferroxidase site.
PMID- 28489259
TI - Molecular alterations in odontogenic keratocysts as potential therapeutic
targets.
AB - The odontogenic keratocyst (OKC) is a cystic lesion, lined by uniformly thickened
parakeratinized epithelium. Some lesions are large and tend to recur after
surgical treatment. The neoplastic nature of OKCs remains a matter of dispute. It
is known that some sporadic OKCs harbor PTCH1 mutations, and via the dissection
of cyst epithelium, these mutations were demonstrated to occur much more
frequently than previously thought. In addition to the classical PTCH1 mutations,
Hedgehog pathway disturbance and Bcl-2 protein overexpression, as detected via
genome-wide expression analysis of OKCs, have been published. Changes in DNA
methylation patterns and alterations in microRNA expression levels have recently
been reported in these lesions. We reviewed the molecular mechanisms that
underlie the pathogenesis of OKCs as described over the past few years and
explored the molecular alterations that can be therapeutically targeted.
PMID- 28489261
TI - C-N Bond Activation and Ring Opening of a Saturated N-Heterocyclic Carbene by
Lateral Alkali-Metal-Mediated Metalation.
AB - Combining alkali-metal-mediated metalation (AMMM) and N-heterocyclic carbene
(NHC) chemistry, a novel C-N bond activation and ring-opening process is
described for these increasingly important NHC molecules, which are generally
considered robust ancillary ligands. Here, mechanistic investigations on
reactions of saturated NHC SIMes (SIMes=[:C{N(2,4,6-Me3 C6 H2 )CH2 }2 ]) with
Group 1 alkyl bases suggest this destructive process is triggered by lateral
metalation of the carbene. Exploiting co-complexation and trans-metal-trapping
strategies with lower polarity organometallic reagents (Mg(CH2 SiMe3 )2 and
Al(TMP)iBu2 ), key intermediates in this process have been isolated and
structurally defined.
PMID- 28489260
TI - Histologic changes associated with talaporfin sodium-mediated photodynamic
therapy in rat skin.
AB - BACKGROUND AND OBJECTIVE: Alternative treatments are needed to achieve consistent
and more complete port wine stain (PWS) removal, especially in darker skin types;
photodynamic therapy (PDT) is a promising alternative treatment. To this end, we
previously reported on Talaporfin Sodium (TS)-mediated PDT. It is essential to
understand treatment tissue effects to design a protocol that will achieve
selective vascular injury without ulceration and scarring. The objective of this
work is to assess skin changes associated with TS-mediated PDT with clinically
relevant treatment parameters. STUDY DESIGN/MATERIALS AND METHODS: We performed
TS (0.75 mg/kg)-mediated PDT (664 nm) on Sprague Dawley rats. Radiant exposures
were varied between 15 and 100 J/cm2 . We took skin biopsies from subjects at 9
hours following PDT. We assessed the degree and depth of vascular and surrounding
tissue injury using histology and immunohistochemical staining. RESULTS: TS
mediated PDT at 0.75 mg/kg combined with 15 and 25 J/cm2 light doses resulted in
vascular injury with minimal epidermal damage. At light dose of 50 J/cm2 ,
epidermal damage was noted with vascular injury. At light doses >50 J/cm2 , both
vascular and surrounding tissue injury were observed in the forms of vasculitis,
extravasated red blood cells, and coagulative necrosis. Extensive coagulative
necrosis involving deeper adnexal structures was observed for 75 and 100 J/cm2
light doses. Observed depth of injury increased with increasing radiant exposure,
although this relationship was not linear. CONCLUSION: TS-mediated PDT can cause
selective vascular injury; however, at higher light doses, significant extra
vascular injury was observed. This information can be used to contribute to
design of safe protocols to be used for treatment of cutaneous vascular lesions.
Lasers Surg. Med. 49:767-772, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28489262
TI - Mechanochemical Friedel-Crafts Alkylation-A Sustainable Pathway Towards Porous
Organic Polymers.
AB - This study elucidates an innovative mechanochemical approach applying Friedel
Crafts alkylation to synthesize porous covalent triazine frameworks (CTFs).
Herein, we pursue a counterintuitive approach by utilizing a rather destructive
method to synthesize well-defined materials with intrinsic porosity.
Investigating a model system including carbazole as monomer and cyanuric chloride
as triazine node, ball milling is shown to successfully yield porous polymers
almost quantitatively. We verified the successful structure formation by an in
depth investigation applying XPS, solid-state NMR and FT-IR spectroscopy. An in
situ study of pressure and temperature developments inside the milling chamber in
combination with two-dimensional liquid-state NMR spectroscopy reveals insights
into the polymerization mechanism. The versatility of this mechanochemical
approach is showcased by application of other monomers with different size and
geometry.
PMID- 28489263
TI - Diagnostic anoctamin-5 protein defect in patients with ANO5-mutated muscular
dystrophy.
AB - AIMS: Previously, detection of ANO5 protein has been complicated by unspecific
antibodies, most of which have not identified the correct protein. The aims of
the study were to specify ANO5 protein expression in human skeletal muscle, and
to investigate if the ANO5 protein levels are affected by different ANO5
mutations in anoctaminopathy patients. METHODS: Four different antibodies were
tested for ANO5 specificity. A sample preparation method compatible with membrane
proteins, combined with tissue fractionation was used to determine ANO5
expression in cell cultures expressing ANO5, in normal muscles and eight patient
biopsies with six different ANO5 mutations in homozygous or compound heterozygous
states, and in other dystrophies. RESULTS: Only one specific monoclonal N
terminal ANO5 antibody was efficient in detecting the protein, showing that ANO5
is expressed as a single 107 kD polypeptide in human skeletal muscle. The
truncating mutations c.191dupA and c.1261C>T were found to abolish ANO5
expression, whereas the studied point mutations had variable effects; however,
all the ANO5 mutations resulted in clearly reduced ANO5 expression in the patient
muscle membrane fraction. Attempts to detect ANO5 using immunohistochemistry were
not yet successful. CONCLUSIONS: The data presented here indicate that the ANO5
protein expression is decreased in ANO5-mutated muscular dystrophy and that most
of the non-truncating pathogenic ANO5 mutations likely destabilize the protein
and cause its degradation. The method described here allows direct analysis of
human ANO5 protein, which can be used in diagnostics, for evaluating the
pathogenicity of the potentially harmful ANO5 variants of uncertain significance.
PMID- 28489264
TI - Critical factors for the recovery of marine mammals.
AB - {en} Over the past decades, much research has focused on understanding the
critical factors for marine extinctions with the aim of preventing further
species losses in the oceans. Although conservation and management strategies are
enabling several species and populations to recover, others remain at low
abundance levels or continue to decline. To understand these discrepancies, we
used a published database on abundance trends of 137 populations of marine
mammals worldwide and compiled data on 28 potentially critical factors for
recovery. We then applied random forests and additive mixed models to determine
which intrinsic and extrinsic factors are critical for the recovery of marine
mammals. A mix of life-history characteristics, ecological traits, phylogenetic
relatedness, population size, geographic range, human impacts, and management
efforts explained why populations recovered or not. Consistently, species with
lower age at maturity and intermediate habitat area were more likely to recover,
which is consistent with life-history and ecological theory. Body size, trophic
level, social interactions, dominant habitat, ocean basin, and habitat
disturbance also explained some differences in recovery patterns. Overall, a
variety of intrinsic and extrinsic factors were important for species' recovery,
pointing to cumulative effects. Our results provide insight for improving
conservation and management strategies to enhance recoveries in the future.
PMID- 28489265
TI - Isolation of Azadiphosphiridines and Diphosphenimines by Cycloaddition of Azides
and a Cationic Diphosphene.
AB - The polarized, cationic diphosphene [(Cl ImDipp )P=P(Dipp)]+ as the triflate salt
7[OTf](Cl ImDipp =4,5-dichloro-1,3-bis(Dipp)-imidazol-2-yl; Dipp=2,6
diisopropylphenyl) reacts with azides of type RN3 (R=Dipp or Dmp; Dmp=2,5
dimethylphenyl) in a [2+3] cycloaddition reaction followed by the release of N2
and a subsequent electrocyclic ring-closing reaction to azadiphosphiridine salts
[(Cl ImDipp )P-P(Dipp)-N(R)]10a,b[OTf] (R=Dipp or Dmp). The reaction of 7[X]
(X=OTf, GaCl4 ) with the electron-rich azides Me3 SiN3 and NaN3 give the unusual
diphosphenimine derivatives [(Cl ImDipp )P-P(Dipp)=N(SiMe3 )]+ (11[OTf]) and [(Cl
ImDipp )P-P(Dipp)=N(GaCl3 )] (12), respectively, featuring an acyclic P2 N
moiety. Theoretical calculations provide insights into the reaction mechanisms to
the cyclic and acyclic forms, in which the thermodynamic stability of the latter
prevents the electrocyclic ring closure.
PMID- 28489266
TI - Redox-Sensitive Stomatocyte Nanomotors: Destruction and Drug Release in the
Presence of Glutathione.
AB - The development of artificial nanomotor systems that are stimuli-responsive is
still posing many challenges. Herein, we demonstrate the self-assembly of a redox
responsive stomatocyte nanomotor system, which can be used for triggered drug
release under biological reducing conditions. The redox sensitivity was
introduced by incorporating a disulfide bridge between the hydrophilic
poly(ethylene glycol) block and the hydrophobic polystyrene block. When incubated
with the endogenous reducing agent glutathione at a concentration comparable to
that within cells, the external PEG shells of these stimuli-responsive nanomotors
are cleaved. The specific bowl-shaped stomatocytes aggregate after the treatment
with glutathione, leading to the loss of motion and triggered drug release. These
novel redox-responsive nanomotors can not only be used for remote transport but
also for drug delivery, which is promising for future biomedical applications.
PMID- 28489267
TI - Visible-Light Photocatalytic Intramolecular Cyclopropane Ring Expansion.
AB - Described herein is a new visible-light photocatalytic strategy for the synthesis
of enantioenriched dihydrofurans and cyclopentenes by an intramolecular nitro
cyclopropane ring expansion reaction. Mechanistic studies and DFT calculations
are used to elucidate the key factors in this new ring expansion reaction, and
the need for the nitro group on the cyclopropane.
PMID- 28489268
TI - Interprotein Electron Transfer between FeS-Protein Nanowires and Oxygen-Tolerant
NiFe Hydrogenase.
AB - Self-assembled redox protein nanowires have been exploited as efficient electron
shuttles for an oxygen-tolerant hydrogenase. An intra/inter-protein electron
transfer chain has been achieved between the iron-sulfur centers of rubredoxin
and the FeS cluster of [NiFe] hydrogenases. [NiFe] Hydrogenases entrapped in the
intricated matrix of metalloprotein nanowires achieve a stable, mediated
bioelectrocatalytic oxidation of H2 at low-overpotential.
PMID- 28489269
TI - Digest: For ecologically similar Andean birds, gene flow and plumage uniformity
go hand in hand.
PMID- 28489270
TI - Controlled Synthesis of Poly(p-phenylene) Using a Zincate Complex, t Bu4 ZnLi2.
AB - Well-defined poly(2,5-dihexyloxyphenylene-1,4-diyl) (PPP) is successfully
synthesized by the Negishi catalyst-transfer polycondensation (NCTP) using
dilithium tetra(tert-butyl)zincate (t Bu4 ZnLi2 ). The obtained PPP possesses the
number-averaged molecular weight (Mn ) values in the range of 2100-22 000 and the
molar-mass dispersity (DM ) values in the range of 1.09-1.23. In addition, block
copolymers containing PPP and poly(3-hexylthiophene) (P3HT) segments (PPP-b-P3HT)
are synthesized to confirm the feasibility of chain extension between the
different monomers based on NCTP.
PMID- 28489271
TI - Successful Treatment of Kaposi Sarcoma-Associated Herpesvirus Inflammatory
Cytokine Syndrome After Kidney-Liver Transplant: Correlations With the Human
Herpesvirus 8 miRNome and Specific T Cell Response.
AB - After transplant, patient infection with human herpesvirus 8 (HHV-8) and Kaposi
sarcoma-associated herpesvirus (KSHV) is known to cause aggressive tumors and
severe nonneoplastic complications. These latter syndromes are driven by HHV
8/KSHV lytic reactivations and related hyperinflammatory host responses typically
characterized by high viral loads, elevated levels of cytokines and other
inflammation biomarkers, cytopenia, organ failure, high fever, and worsening
conditions (with no evidence of B cell neoplasias). These disorders are
associated with a high mortality rate, often due to lack of prompt diagnosis,
effective therapeutic approaches, and adequate follow-up. These features resemble
most of those defining the so-called KSHV-associated inflammatory cytokine
syndrome (KICS), which was recently recognized in patients positive for human
immunodeficiency virus (HIV). In this report, we describe-for the first time-a
case of a KICS-like nonneoplastic recurrent complication occurring after
transplant in an HIV-negative patient that was successfully treated by a
combination of anti-CD20 monoclonal therapy, antivirals, and modification of the
immunosuppressive regimen. In addition to clinical and laboratory findings
collected during 3-year follow-up, we report novel experimental data on HHV-8
specific T cell dynamics and circulating microRNA profile, showing correlations
with clinical course and other laboratory markers (including viral load, C
reactive protein, and cytokine levels), providing useful information about
abnormal cellular and cytokine dynamics underlying HHV-8-associated inflammatory
disorders in posttransplant patients.
PMID- 28489272
TI - Fear learning alterations after traumatic brain injury and their role in
development of posttraumatic stress symptoms.
AB - BACKGROUND: It is unknown how traumatic brain injury (TBI) increases risk for
posttraumatic stress disorder (PTSD). One potential mechanism is via alteration
of fear-learning processes that could affect responses to trauma memories and
cues. We utilized a prospective, longitudinal design to determine if TBI is
associated with altered fear learning and extinction, and if fear processing
mediates effects of TBI on PTSD symptom change. METHODS: Eight hundred fifty two
active-duty Marines and Navy Corpsmen were assessed before and after deployment.
Assessments included TBI history, PTSD symptoms, combat trauma and deployment
stress, and a fear-potentiated startle task of fear acquisition and extinction.
Startle response and self-reported expectancy and anxiety served as measures of
fear conditioning, and PTSD symptoms were measured with the Clinician
Administered PTSD Scale. RESULTS: Individuals endorsing "multiple hit" exposure
(both deployment TBI and a prior TBI) showed the strongest fear acquisition and
highest fear expression compared to groups without multiple hits. Extinction did
not differ across groups. Endorsing a deployment TBI was associated with higher
anxiety to the fear cue compared to those without deployment TBI. The association
of deployment TBI with increased postdeployment PTSD symptoms was mediated by
postdeployment fear expression when recent prior-TBI exposure was included as a
moderator. TBI associations with increased response to threat cues and PTSD
symptoms remained when controlling for deployment trauma and postdeployment PTSD
diagnosis. CONCLUSIONS: Deployment TBI, and multiple-hit TBI in particular, are
associated with increases in conditioned fear learning and expression that may
contribute to risk for developing PTSD symptoms.
PMID- 28489273
TI - Low level light-minoxidil 5% combination versus either therapeutic modality alone
in management of female patterned hair loss: A randomized controlled study.
AB - BACKGROUND: Female pattern hair loss (FPHL) is the most common form of hair loss
in women. Nevertheless, its management represents a real challenge. Among the FDA
approved therapeutic modalities for FPHL are topical minoxidil and more recently
low-level light therapy (LLLT). AIM OF WORK: Assess the efficacy and safety of
LLLT in comparison to topical minoxidil 5% and to a combination of both therapies
in the treatment of FPHL. PATIENTS AND METHODS: This study included 45 female
patients with proven FPHL. They were randomly divided into three equal groups,
where group (i) patients were instructed to apply topical minoxidil 5% twice
daily, group (ii) patients received LLLT using the helmet iGrow(r) device for 25
minutes 3 days weekly, and group (iii) patients received a combination of both
topical minoxidil 5% twice daily and LLLT for 25 minutes 3 days weekly for 4
months (study duration). Evaluation was done according to clinical, dermoscopic
(folliscopic), and ultrasound bio-microscopic (UBM) parameters. Patient
satisfaction and side effects were reported. RESULTS: The efficacy and safety of
both topical minoxidil and LLLT were highlighted with comparable results in all
parameters. The combination group (iii) occupied the top position regarding
Ludwig classification and patient satisfaction. UBM and dermoscopic findings
showed significant increase in the number of regrowing hair follicles at 4 months
in all groups, whereas only UBM showed such significant increase at 2 months in
the combination group (iii). A non-significant increase in the hair diameter was
also documented in the three groups. CONCLUSION: LLLT is an effective and safe
tool with comparable results to minoxidil 5% in the treatment of FPHL. Owing to
the significantly better results of combination therapy, its usage is recommended
to hasten hair regrowth. Lasers Surg. Med. 49:835-843, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28489274
TI - Ultrasound Imaging Based on Molecular Targeting for Quantitative Evaluation of
Hepatic Ischemia-Reperfusion Injury.
AB - The aim of the present study was to quantitatively diagnose and monitor the
therapy response of hepatic ischemia-reperfusion injury (IRI) with the use of
targeted ultrasound (US) imaging. Targeted microbubbles (MBs) were fabricated,
and the binding of intracellular adhesion molecule 1 (ICAM-1) antibodies to MBs
was observed. To establish a quantitative method based on targeted US imaging,
contrast-enhanced US was applied for IRI rats. After andrographolide treatment,
the IRI rats were subjected to the quantitative targeted US imaging for a
therapeutic effect. Effective binding of ICAM-1 antibodies to MBs was observed.
According to the quantitative targeted US imaging, the ICAM-1 normalized
intensity difference (NID) in the IRI rats (38.74 +/- 15.08%) was significantly
higher than that in the control rats (10.08 +/- 2.52%, p = 0.048). Further,
different degrees of IRI (mild IRI, moderate to severe IRI) were distinguished by
the use of the NID (37.14 +/- 2.14%, 22.34 +/- 1.08%, p = 0.002). Analysis of
mRNA expression demonstrated the accuracy of analyzing the NID by using
quantitative targeted US imaging (R2 = 0.7434, p < 0.001). Andrographolide
treatment resulted in an obviously weakened NID of ICAM-1 (17.7 +/- 4.8% vs 34.2
+/- 6.6%, p < 0.001). The study showed the potential of the quantitative targeted
US imaging method for the diagnosis and therapeutic monitoring of IRI.
PMID- 28489275
TI - Recent drug therapies for corneal neovascularization.
AB - Corneal neovascularization (CNV) is a common pathological change in ocular
surface diseases. It is not only the factor that affects vision but also the main
cause for corneal graft failure. Based on the mechanism of CNV, many achievements
have been developed to suppress the formation of CNV. There are certain novel
drugs such as aflibercept, gold nanoparticles, and netrins which provide us with
new clues to treat CNV. However, we still need to develop more effective
therapeutic drugs. It is of great significance to develop new effective drugs to
suppress the occurrence of CNV. In this paper, recent drug therapies for CNV are
reviewed. The electronic database (PubMed) is searched for relative basic
research and randomized clinical trials that are published recently.
PMID- 28489276
TI - Design, synthesis, and preliminary bioactivity evaluation of N-benzylpyrimidin-2
amine derivatives as novel histone deacetylase inhibitor.
AB - Histone deacetylase (HDAC) inhibitors have been identified for the treatment of
cancer. Lately, we designed and synthesized a series of substituted N
benzylpyrimidin-2-amine derivatives as potent HDAC inhibitors. In vitro HDAC
inhibitory activities and antiproliferative activities of target compounds were
investigated. Some target compounds showed potent HDAC inhibitory activities and
possessed obvious antiproliferative activity against tumor cells. Target
compounds 6a, 6d, 8a, 8c, and 8f not only exhibited almost equally enzymatic
inhibitory activity with SAHA, but showed better antiproliferative activities.
PMID- 28489277
TI - Pancreas-After-Islet Transplantation in Nonuremic Type 1 Diabetes: A Strategy for
Restoring Durable Insulin Independence.
AB - Islet transplantation offers a minimally invasive approach for beta cell
replacement in diabetic patients with hypoglycemic unawareness. Attempts at
insulin independence may require multiple islet reinfusions from distinct donors,
increasing the risk of allogeneic sensitization. Currently, solid organ pancreas
transplant is the only remaining surgical option following failed islet
transplantation in the United States; however, the immunologic impact of repeated
exposure to donor antigens on subsequent pancreas transplantation is unclear. We
describe a case series of seven patients undergoing solid organ pancreas
transplant following islet graft failure with long-term follow-up of pancreatic
graft survival and renal function. Despite highly variable panel reactive
antibody levels prior to pancreas transplant (mean 27 +/- 35%), all seven
patients achieved stable and durable insulin independence with a mean follow-up
of 6.7 years. Mean hemoglobin A1c values improved significantly from postislet,
prepancreas levels (mean 8.1 +/- 1.5%) to postpancreas levels (mean 5.3 +/- 0.1%;
p = 0.0022). Three patients experienced acute rejection episodes that were
successfully managed with thymoglobulin and methylprednisolone, and none of these
preuremic type 1 diabetic recipients developed stage 4 or 5 chronic kidney
disease postoperatively. These results support pancreas-after-islet
transplantation with aggressive immunosuppression and protocol biopsies as a
viable strategy to restore insulin independence after islet graft failure.
PMID- 28489278
TI - Growth of indoor fungi on gypsum.
AB - AIMS: To have a better understanding of fungal growth on gypsum building
materials to prevent indoor fungal growth. METHODS AND RESULTS: Gypsum is
acquired by mining or as a by-product of flue-gas desulphurization or treatment
of phosphate ore for the production of fertilizer. Natural gypsum, flue-gas
gypsum and phosphogypsum therefore have different mineral compositions. Here,
growth of fungi on these types of gypsum was assessed. Conidia of the indoor
fungi Aspergillus niger, Cladosporium halotolerans and Penicillium rubens were
inoculated and observed using microscopic techniques including low-temperature
scanning electron microscopy. Elemental analysis of gypsum was done using
inductively coupled plasma atomic emission spectroscopy and segmented flow
analysis. Moisture content of the gypsum was determined using a dynamic vapour
sorption apparatus. Aspergillus niger, C. halotolerans and P. rubens hardly
germinated on natural gypsum and flue-gas gypsum. The latter two fungi did show
germination, outgrowth, and conidiation on phosphogypsum, while A. niger hardly
germinated on this substrate. Other experiments show that C. halotolerans and P.
rubens can develop in pure water, but A. niger does not. CONCLUSIONS: The
observations show that the lack of germination of three indoor fungi is explained
by the low amount of phosphor in natural, flue-gas and laboratory-grade gypsum.
Additionally, C. halotolerans and P. rubens can develop in pure water, while
conidia of A. niger do not show any germination, which is explained by the need
for organic molecules of this species to induce germination. SIGNIFICANCE AND
IMPACT OF THE STUDY: Indoor fungal growth is a potential threat to human health
and causes damage to building materials. This study possibly helps in the
application of the right type of gypsum in buildings.
PMID- 28489280
TI - Synthesis and evaluation of cytotoxic activities of artemisinin derivatives.
AB - Artemisinin is a naturally occurring antimalarial agent which has shown potent
anticancer activity. In this work, new artemisinin derivatives with the
piperazine group were synthesized. The cytotoxic activities of derivatives 5a-5d
were evaluated by MTT assay against ten cell lines. The results showed that 5a-5d
were more effective in inhibiting cancer cell growth than artemisinin. 5d was the
most active against HepG2 and PLC-PRF-5 cells and presented no cytotoxicity on L
02 cells. Hoechst 33342 staining and flow cytometry experiment revealed that 5d
could induce HepG2 and PLC-PRF-5 cell apoptosis. Flow cytometry analysis showed
that 5d induced the loss of mitochondrial membrane potential (MMP) and increased
the levels of intracellular free calcium and reactive oxygen species. 5d also
induced cell cycle arrest in G2/M phase in HepG2 cells. According to the results
of Western blotting and caspase-3 kit, 5d could significantly increase the
content of p53, bax, Apaf-1, and caspase-3 and decrease the protein level of bcl
2, pro-caspase-9, and pro-caspase-3 in HepG2 cells. These findings indicate that
5d activates the mitochondria-mediated apoptotic pathway in HepG2 cells and may
merit further investigation as a potential therapeutic agent for hepatocellular
carcinoma.
PMID- 28489279
TI - Dipeptidyl-peptidase (DPP)-4 inhibitors and glucagon-like peptide (GLP)-1
analogues for prevention or delay of type 2 diabetes mellitus and its associated
complications in people at increased risk for the development of type 2 diabetes
mellitus.
AB - BACKGROUND: The projected rise in the incidence of type 2 diabetes mellitus
(T2DM) could develop into a substantial health problem worldwide. Whether
dipeptidyl-peptidase (DPP)-4 inhibitors or glucagon-like peptide (GLP)-1
analogues are able to prevent or delay T2DM and its associated complications in
people at risk for the development of T2DM is unknown. OBJECTIVES: To assess the
effects of DPP-4 inhibitors and GLP-1 analogues on the prevention or delay of
T2DM and its associated complications in people with impaired glucose tolerance,
impaired fasting blood glucose, moderately elevated glycosylated haemoglobin A1c
(HbA1c) or any combination of these. SEARCH METHODS: We searched the Cochrane
Central Register of Controlled Trials; MEDLINE; PubMed; Embase;
ClinicalTrials.gov; the World Health Organization (WHO) International Clinical
Trials Registry Platform; and the reference lists of systematic reviews, articles
and health technology assessment reports. We asked investigators of the included
trials for information about additional trials. The date of the last search of
all databases was January 2017. SELECTION CRITERIA: We included randomised
controlled trials (RCTs) with a duration of 12 weeks or more comparing DPP-4
inhibitors and GLP-1 analogues with any pharmacological glucose-lowering
intervention, behaviour-changing intervention, placebo or no intervention in
people with impaired fasting glucose, impaired glucose tolerance, moderately
elevated HbA1c or combinations of these. DATA COLLECTION AND ANALYSIS: Two review
authors read all abstracts and full-text articles and records, assessed quality
and extracted outcome data independently. One review author extracted data which
were checked by a second review author. We resolved discrepancies by consensus or
the involvement of a third review author. For meta-analyses, we planned to use a
random-effects model with investigation of risk ratios (RRs) for dichotomous
outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence
intervals (CIs) for effect estimates. We assessed the overall quality of the
evidence using the GRADE instrument. MAIN RESULTS: We included seven completed
RCTs; about 98 participants were randomised to a DPP-4 inhibitor as monotherapy
and 1620 participants were randomised to a GLP-1 analogue as monotherapy. Two
trials investigated a DPP-4 inhibitor and five trials investigated a GLP-1
analogue. A total of 924 participants with data on allocation to control groups
were randomised to a comparator group; 889 participants were randomised to
placebo and 33 participants to metformin monotherapy. One RCT of liraglutide
contributed 85% of all participants. The duration of the intervention varied from
12 weeks to 160 weeks. We judged none of the included trials at low risk of bias
for all 'Risk of bias' domains and did not perform meta-analyses because there
were not enough trials.One trial comparing the DPP-4 inhibitor vildagliptin with
placebo reported no deaths (very low-quality evidence). The incidence of T2DM by
means of WHO diagnostic criteria in this trial was 3/90 participants randomised
to vildagliptin versus 1/89 participants randomised to placebo (very low-quality
evidence). Also, 1/90 participants on vildagliptin versus 2/89 participants on
placebo experienced a serious adverse event (very low-quality evidence). One out
of 90 participants experienced congestive heart failure in the vildagliptin group
versus none in the placebo group (very low-quality evidence). There were no data
on non-fatal myocardial infarction, stroke, health-related quality of life or
socioeconomic effects reported.All-cause and cardiovascular mortality following
treatment with GLP-1 analogues were rarely reported; one trial of exenatide
reported that no participant died. Another trial of liraglutide 3.0 mg showed
that 2/1501 in the liraglutide group versus 2/747 in the placebo group died after
160 weeks of treatment (very low-quality evidence).The incidence of T2DM
following treatment with liraglutide 3.0 mg compared to placebo after 160 weeks
was 26/1472 (1.8%) participants randomised to liraglutide versus 46/738 (6.2%)
participants randomised to placebo (very low-quality evidence). The trial
established the risk for (diagnosis of) T2DM as HbA1c 5.7% to 6.4% (6.5% or
greater), fasting plasma glucose 5.6 mmol/L or greater to 6.9 mmol/L or less (7.0
mmol/L or greater) or two-hour post-load plasma glucose 7.8 mmol/L or greater to
11.0 mmol/L (11.1 mmol/L). Altogether, 70/1472 (66%) participants regressed from
intermediate hyperglycaemia to normoglycaemia compared with 268/738 (36%)
participants in the placebo group. The incidence of T2DM after the 12-week off
treatment extension period (i.e. after 172 weeks) showed that five additional
participants were diagnosed T2DM in the liraglutide group, compared with one
participant in the placebo group. After 12-week treatment cessation, 740/1472
(50%) participants in the liraglutide group compared with 263/738 (36%)
participants in the placebo group had normoglycaemia.One trial used exenatide and
2/17 participants randomised to exenatide versus 1/16 participants randomised to
placebo developed T2DM (very low-quality evidence). This trial did not provide a
definition of T2DM. One trial reported serious adverse events in 230/1524 (15.1%)
participants in the liraglutide 3.0 mg arm versus 96/755 (12.7%) participants in
the placebo arm (very low quality evidence). There were no serious adverse events
in the trial using exenatide. Non-fatal myocardial infarction was reported in
1/1524 participants in the liraglutide arm and in 0/55 participants in the
placebo arm at 172 weeks (very low-quality evidence). One trial reported
congestive heart failure in 1/1524 participants in the liraglutide arm and in
1/755 participants in the placebo arm (very low-quality evidence). Participants
receiving liraglutide compared with placebo had a small mean improvement in the
physical component of the 36-item Short Form scale showing a difference of 0.87
points (95% CI 0.17 to 1.58; P = 0.02; 1 trial; 1791 participants; very low
quality evidence). No trial evaluating GLP-1-analogues reported data on stroke,
microvascular complications or socioeconomic effects. AUTHORS' CONCLUSIONS: There
is no firm evidence that DPP-4 inhibitors or GLP-1 analogues compared mainly with
placebo substantially influence the risk of T2DM and especially its associated
complications in people at increased risk for the development of T2DM. Most
trials did not investigate patient-important outcomes.
PMID- 28489282
TI - Collaborative writing applications in healthcare: effects on professional
practice and healthcare outcomes.
AB - BACKGROUND: Collaborative writing applications (CWAs), such as wikis and Google
Documents, hold the potential to improve the use of evidence in both public
health and healthcare. Although a growing body of literature indicates that CWAs
could have positive effects on healthcare, such as improved collaboration,
behavioural change, learning, knowledge management, and adaptation of knowledge
to local context, this has never been assessed systematically. Moreover, several
questions regarding safety, reliability, and legal aspects exist. OBJECTIVES: The
objectives of this review were to (1) assess the effects of the use of CWAs on
process (including the behaviour of healthcare professionals) and patient
outcomes, (2) critically appraise and summarise current evidence on the use of
resources, costs, and cost-effectiveness associated with CWAs to improve
professional practices and patient outcomes, and (3) explore the effects of
different CWA features (e.g. open versus closed) and different implementation
factors (e.g. the presence of a moderator) on process and patient outcomes.
SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and 11 other electronic
databases. We searched the grey literature, two trial registries, CWA websites,
individual journals, and conference proceedings. We also contacted authors and
experts in the field. We did not apply date or language limits. We searched for
published literature to August 2016, and grey literature to September 2015.
SELECTION CRITERIA: We included randomised controlled trials (RCTs), non
randomised controlled trials (NRCTs), controlled before-and-after (CBA) studies,
interrupted time series (ITS) studies, and repeated measures studies (RMS), in
which CWAs were used as an intervention to improve the process of care, patient
outcomes, or healthcare costs. DATA COLLECTION AND ANALYSIS: Teams of two review
authors independently assessed the eligibility of studies. Disagreements were
resolved by discussion, and when consensus was not reached, a third review author
was consulted. MAIN RESULTS: We screened 11,993 studies identified from the
electronic database searches and 346 studies from grey literature sources. We
analysed the full text of 99 studies. None of the studies met the eligibility
criteria; two potentially relevant studies are ongoing. AUTHORS' CONCLUSIONS:
While there is a high number of published studies about CWAs, indicating that
this is an active field of research, additional studies using rigorous
experimental designs are needed to assess their impact and cost-effectiveness on
process and patient outcomes.
PMID- 28489281
TI - Unveiling microbial interactions in stratified mat communities from a warm saline
shallow pond.
AB - Modern phototrophic microbial mats are complex communities often used as analogs
of major Precambrian ecosystems. Characterizing biotic, notably metabolic,
interactions among different microbial mat members is essential to gain insights
into the ecology and biogeochemistry of these systems. We applied 16S/18S rRNA
metabarcoding approaches to characterize the structure of archaea, bacteria and
protist communities from microbial mats collected along strong physicochemical
(oxygen, salinity, temperature, depth) gradients in a shallow pond at the salar
de Llamara (Chile). All mats were highly diverse, including members of virtually
all known high-rank eukaryotic and prokaryotic taxa but also many novel lineages.
Bacterial candidate divisions accounted for almost 50% of sequences in deeper
mats, while Archaea represented up to 40% of sequences in some mat layers.
Molecular phylogenetic analyses revealed six novel deeply divergent archaeal
groups, along abundant and diverse Pacearchaeota and Woesearchaeota. Multivariate
statistical analyses showed that local environmental conditions strongly
influenced community composition. Co-occurrence network structure was markedly
different between surface mats located in the oxygenated zone and mats located in
transition and anoxic water layers. We identified potential biotic interactions
between various high- and low-rank taxa. Notably, a strong positive correlation
was observed between Lokiarchaeota and the poorly known candidate bacterial
division TA06.
PMID- 28489283
TI - Inflammatory responses, matrix remodeling, and re-epithelialization after
fractional CO2 laser treatment of scars.
AB - BACKGROUND AND OBJECTIVE: Fractional CO2 laser therapy has been used to improve
scar pliability and appearance; however, a variety of treatment protocols have
been utilized with varied outcomes. Understanding the relationship between laser
power and extent of initial tissue ablation and time frame for remodeling could
help determine an optimum power and frequency for laser treatment. The
characteristics of initial injury caused by fractional CO2 laser treatment, the
rates of dermal remodeling and re-epithelialization, and the extent of
inflammation as a function of laser stacking were assessed in this study in a
porcine scar model. MATERIALS AND METHODS: Full-thickness burn wounds were
created on female Red Duroc pigs followed by immediate excision of the eschar and
split-thickness autografting. Three months after injury, the resultant scars were
treated with a fractional CO2 laser with 70 mJ of energy delivered as either a
single pulse or stacked for three consecutive pulses. Immediately prior to laser
treatment and at 1, 24, 96, and 168 hours post-laser treatment, transepidermal
water loss (TEWL), erythema, and microscopic characteristics of laser injury were
measured. In addition, markers for inflammatory cytokines, extracellular matrix
proteins, and re-epithelialization were quantified at all time points using qRT
PCR. RESULTS: Both treatments produced erythema in the scar that peaked 24 hours
after treatment then decreased to basal levels by 168 hours. TEWL increased after
laser treatment and returned to normal levels between 24 and 96 hours later.
Stacking of the pulses did not significantly increase the depth of ablated wells
or extend the presence of erythema. Interleukin 6 and monocyte chemoattractant
protein-1 were found to increase significantly 1 hour after treatment but
returned to baseline by 24 hours post laser. In contrast, expression of
transforming growth factor beta1 and transforming growth factor beta3 increased
slowly after treatment with a more modest increase than interleukin 6 and
monocyte chemoattractant protein-1. CONCLUSIONS: In the current study, the
properties of the ablative zones were not directly proportional to the total
amount of energy applied to the porcine scars with the use of triple stacking,
resulting in only minor increases to microthermal zone (MTZ) depth and width
versus a single pulse. Re-epithelialization and re-establishment of epidermal
barrier function were observed in laser treated scars by 48 hours post therapy.
Finally, many of the inflammatory genes up-regulated by the laser ablation
returned to baseline within 1 week. As a whole, these results suggest that
microthermal zones created by FXCO2 treatment re-epithelialize rapidly with the
inflammatory response to the laser induced injury largely resolved within 1 week
post treatment. Further study is needed to understand the relationship between
laser stacking and MTZ properties in human scars in order to evaluate the
clinical applicability of the stacking technique. Lasers Surg. Med. 49:675-685,
2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28489284
TI - Mapping genotype-phenotype associations of nsSNPs in coiled-coil oligomerization
domains of the human proteome.
AB - We assessed the impact of disease mutations (DMs) versus polymorphisms (PYs) in
coiled-coil (CC) domains in UniProt by modeling the structural and functional
impact of variants in silico with the CC prediction program Multicoil. The
structural impact of variants was evaluated with respect to three main metrics:
the oligomerization score-to determine whether the variant is stabilizing or
destabilizing-the oligomerization state, and the register-specific score. The
functional impact was queried indirectly in several ways. First, we examined
marginally stable CCs that were either stabilized or destabilized by the variant.
Second, we looked for variants that altered the register of the wild-type CC near
wild-type irregularities of likely functional importance, such as skips and
stammers. Third, we searched for variants that altered the oligomerization state
of the CC. DMs tended to be more destabilizing than PYs; but interestingly, PYs
were more frequently associated with predicted changes in the oligomerization
state. The functional impact was also queried by testing the association of CC
variants with multiple phenotypes, that is, pleiotropy. Mutations in CC regions
of proteins cause 155 different phenotypes and are more frequently associated
with pleiotropy than proteins in general. Importantly, the CC region itself often
encodes the pleiotropy.
PMID- 28489285
TI - SCAI appropriate use criteria for peripheral arterial interventions: An update.
PMID- 28489287
TI - Broken Chains and Reneging: A Review of 1748 Kidney Paired Donation Transplants.
AB - Concerns regarding the potential for broken chains and "reneges" within kidney
paired donation (KPD) and its effect on chain length have been raised previously.
Although these concerns have been tested in simulation studies, real-world data
have yet to be evaluated. The purpose of this study was to evaluate the actual
rate and causes of broken chains within a large KPD program. All patients
undergoing renal transplantation through the National Kidney Registry from 2008
through May 2016 were included for analysis. Broken chains and loops were
identified. A total of 344 chains and 78 loops were completed during the study
period, yielding a total of 1748 transplants. Twenty broken chains and one broken
loop were identified. The mean chain length (number of transplants) within broken
chains was 4.8 compared with 4.6 of completed chains (p = 0.78). The most common
causes of a broken chain were donor medical issues incurred while acting as a
bridge donor (n = 8), donors electing not to proceed (n = 6), and kidneys being
declined by the recipient surgeon (n = 4). All recipients involved in a broken
chain subsequently received a transplant. Based on the results, broken chains are
infrequent, are rarely due to lack of donor motivation, and have no significant
impact on chain length.
PMID- 28489286
TI - Sustained activation of ERK1/2 MAPK in Schwann cells causes corneal neurofibroma.
AB - Recent studies have shown that constitutive activation of extracellular signal
regulated kinases 1 and 2 (ERK1/2) in Schwann cells (SCs) increases myelin
thickness in transgenic mice. In this secondary analysis, we report that these
transgenic mice develop a postnatal corneal neurofibroma with the loss of corneal
transparency by age six months. We show that expansion of non-myelinating SCs,
under the control of activated ERK1/2, also drive myofibroblast differentiation
that derives from both SC precursors and resident corneal keratocytes. Further,
these mice also harbor activated mast cells in the central cornea, which
contributes to pathological corneal neovascularization and fibrosis. This breach
of corneal avascularity and immune status is associated with the growth of the
tumor pannus, resulting in a corneal stroma that is nearly four times its normal
size. In corneas with advanced disease, some axons became ectopically myelinated,
and the disruption of Remak bundles is evident. To determine whether
myofibroblast differentiation was linked to vimentin, we examined the levels and
phosphorylation status of this fibrotic biomarker. Concomitant with the early
upregulation of vimentin, a serine 38-phosphorylated isoform of vimentin
(pSer38vim) increased in SCs, which was attributed primarily to the soluble
fraction of protein-not the cytoskeletal portion. However, the overexpressed
pSer38vim became predominantly cytoskeletal with the growth of the corneal tumor.
Our findings demonstrate an unrecognized function of ERK1/2 in the maintenance of
corneal homeostasis, wherein its over-activation in SCs promotes corneal
neurofibromas. This study is also the first report of a genetically engineered
mouse that spontaneously develops a corneal tumor.
PMID- 28489288
TI - Enhanced cognitive behavioral therapy for eating disorders adapted for a group
setting.
AB - OBJECTIVE: This randomized control trial is an evaluation of the effectiveness of
enhanced cognitive behavioral treatment (CBT-E) for eating disorders adapted for
a group setting. The study aimed to examine the effects of group CBT-E on eating
disorder psychopathology and additional maintaining pathology. METHOD: A
transdiagnostic sample of individuals with eating disorders with a BMI >= 18
kg/m2 (N = 40) were randomized to an immediate-start or delayed-start condition
so as to compare therapeutic effects of group CBT-E with a waitlist control.
Global Eating Disorder Examination Questionnaire (EDE-Q) scores, BMI, and
measures of Clinical Perfectionism, Self-Esteem, Interpersonal Difficulties, and
Mood Intolerance were measured across the 8-week control period, throughout the
group treatment and at 3-months post-treatment. RESULTS: Over 70% of those who
entered the trial completed treatment. The first eight weeks of group CBT-E were
more effective at reducing Global EDE-Q scores than no treatment (waitlist
control). By post-treatment, good outcome (a Global EDE-Q within 1 SD of
Australian community norms plus BMI >= 18.5) was achieved by 67.9% of treatment
completers and 66.7% of the total sample. Symptom abstinence within the previous
month was reported by 14.3% of treatment completers and 10.3% of the total
sample. Significant reductions in Clinical Perfectionism, Self-Esteem,
Interpersonal Difficulties, and Mood Intolerance were also observed. DISCUSSION:
This study demonstrated that a group version of CBT-E can be effective at
reducing eating disorder psychopathology in a transdiagnostic sample of
individuals with eating disorders. Group CBT-E could provide a means of
increasing availability of evidence-based treatment for eating disorders.
PMID- 28489289
TI - Introducing high-flow nasal cannula to the neonatal transport environment.
PMID- 28489290
TI - Obesity: a chronic relapsing progressive disease process. A position statement of
the World Obesity Federation.
AB - This paper considers the argument for obesity as a chronic relapsing disease
process. Obesity is viewed from an epidemiological model, with an agent affecting
the host and producing disease. Food is the primary agent, particularly foods
that are high in energy density such as fat, or in sugar-sweetened beverages. An
abundance of food, low physical activity and several other environmental factors
interact with the genetic susceptibility of the host to produce positive energy
balance. The majority of this excess energy is stored as fat in enlarged, and
often more numerous fat cells, but some lipid may infiltrate other organs such as
the liver (ectopic fat). The enlarged fat cells and ectopic fat produce and
secrete a variety of metabolic, hormonal and inflammatory products that produce
damage in organs such as the arteries, heart, liver, muscle and pancreas. The
magnitude of the obesity and its adverse effects in individuals may relate to the
virulence or toxicity of the environment and its interaction with the host. Thus,
obesity fits the epidemiological model of a disease process except that the toxic
or pathological agent is food rather than a microbe. Reversing obesity will
prevent most of its detrimental effects.
PMID- 28489291
TI - Long-term outcomes of early compared to late onset choledochocholedochal
anastomotic strictures after orthotopic liver transplantation.
AB - BACKGROUND: Endoscopic treatment of anastomotic biliary stricture (ABS) after
liver transplantation (LT) has been proven to be effective and safe, but long
term outcomes of early compared to late onset ABS have not been studied. The aim
of this study is to compare the long-term outcome of early ABS to late ABS.
METHODS: Of the 806 adult LT recipients (04/2006-12/2012), 93 patients met the
criteria for inclusion, and were grouped into non-ABS (no stenosis on ERCP,
n=41), early ABS (stenosis <90 days after LT, 18 [19.3%]), and late ABS (stenosis
>=90 days after LT, 34 [36.5%]). A propensity matched control group for the ABS
group (n=42) was obtained matched for outcome variables for age, gender, and
calculated MELD score at listing. RESULTS: Mean number of ERCPs (2.33+/-1.3 vs
2.56+/-1.5, P=.69) were comparable between the groups; however, significantly
better long-term resolution of the stricture was noted in the early ABS group
(94.44% vs 67.65%, P=.04). Kaplan-Meier analysis revealed worst survival in the
early ABS group compared to the non-ABS, late ABS, and control groups (P=.0001).
CONCLUSION: LT recipients with early ABS have inferior graft survival despite
better response to endoscopic intervention.
PMID- 28489292
TI - Dual Stimuli-Responsive Nanoparticles for Controlled Release of Anticancer and
Anti-inflammatory Drugs Combination.
AB - Dual stimuli-responsive nanoparticles capable of fine-tuning drug release to
augment therapeutic efficacy have become a promising tool for anticancer drug
delivery. However, the rational design of these "smart" nanoparticles for a
selective delivery and controlled release of multidrug combinations in cancer
cells to achieve synergistic effects remain challenging. Here we report the
pH/redox dual responsive nanoparticle FA-DOX-Ind-NP (FA=folic acid,
DOX=doxorubicin, Ind=indomethacin, NP=nanoparticle) based on the novel tumor
targeting and biodegradable poly(beta-amino ester) polymer, and demonstrate its
high ability to enter into cancer cells and release a combination of the
anticancer drug doxorubicin and the non-steroidal anti-inflammatory drug
indomethacin to achieve synergistic chemo-anti-inflammatory effects and overcome
multidrug resistance. This study highlights the great potential of tumor
targeting and dual stimuli-responsive nanoparticles for an efficient delivery of
multidrug combination to improve the cancer therapeutic efficacy.
PMID- 28489294
TI - A Transparent, Highly Stretchable, Autonomous Self-Healing Poly(dimethyl
siloxane) Elastomer.
AB - An innovative self-healing polydimethylsiloxane (PDMS) elastomer, namely, PDMS
TFB, is reported by incorporating the reversibly dynamic imine bond as the self
healing points into the PDMS networks. The PDMS-TFB elastomer features good
optical transmittance (80%) in full visible light region, high stretchability
(~700%), and excellent autonomous self-healing ability at room temperature.
Surprisingly, the self-healing behavior can take place in water and even at a
temperature as low as -20 degrees C in air, showing a promising outlook for
broader applications. As a proof-of-concept, this study demonstrates the use of
the PDMS-TFB elastomer for preparing anticorrosion coating and adhesive layer,
and also the use of such an elastomer to be the platform for fabricating the
flexible interconnector and chemical sensor. Remarkably, no significant
difference is observed between the pristine and healed samples. Taking full
advantage of these unique properties, it is anticipated that such a PDMS-TFB
elastomer shows wide applications in the fields of materials science,
electronics, biology, optics, etc.
PMID- 28489295
TI - A pH-Responsive DNAsome from the Self-Assembly of DNA-Phenyleneethynylene Hybrid
Amphiphile.
AB - A pH-responsive DNAsome derived from the amphiphilicity-driven self-assembly of
DNA amphiphile containing C-rich DNA sequence is reported. The acidification of
DNAsome induces a structural change of C-rich DNA from random coil to an i-motif
structure that triggers the disassembly of DNAsome and its subsequent
morphological transformation into an open entangled network. The encapsulation of
a hydrophobic guest into the membrane of DNAsome and its pH-triggered release
upon acidification of DNAsome is also demonstrated.
PMID- 28489293
TI - The role of family history of depression and the menopausal transition in the
development of major depression in midlife women: Study of women's health across
the nation mental health study (SWAN MHS).
AB - BACKGROUND: This study evaluated whether family history of depression predicts
major depression in midlife women above and beyond static risk factors (such as
personal history of depression prior to midlife) and risks that may change
dynamically across midlife (such as menopausal, psychosocial, and health
profiles). METHODS: Participants were 303 African American and Caucasian women
(42-52 years at baseline) recruited into the Study of Women's Health across the
Nation (SWAN) Mental Health Study (MHS) in Pittsburgh. Major depression was
assessed annually with Structured Clinical Interviews for DSM-IV. Family mental
health history was collected at the ninth or tenth annual follow-up. Random
effects logistic regression was used to assess the relationship between family
history of depression and midlife depression, controlling for baseline
sociodemographic characteristics and time-varying risk factors. RESULTS: Family
history of depression was associated with midlife depression after adjusting for
participant's history of major depression prior to midlife, trait anxiety and
baseline age, and time-varying menopausal status, body mass index, very upsetting
life events, and chronic difficulties (OR = 2.24, 95% CI = 1.17-4.29, P = .02).
Higher odds of major depression were found when women were late perimenopausal or
postmenopausal relative to when they were premenopausal or early perimenopausal
(OR = 3.01, 95% CI = 1.76-5.15, P < .0001). However, menopausal status was only
associated with major depression among women without a family history.
CONCLUSIONS: Family history of depression predicts major depression in midlife
women independent of the menopausal transition and other time-varying covariates.
Notably, the menopausal transition was associated with increased risk only among
women without a family history of depression.
PMID- 28489296
TI - Rapid actions of oestrogens and their receptors on memory acquisition and
consolidation in females.
AB - Increased attention has been paid in recent years to the ways in which oestrogens
and oestrogen receptors rapidly affect learning and memory. These rapid effects
occur within a timeframe that is too narrow for the classical genomic mode of
action of oestrogen, thus suggesting nonclassical effects as underlying
mechanisms. The present review examines recent developments in the study of the
rapid effects of 17beta-oestradiol and oestrogen receptor (ER) agonists on
learning and memory tasks in female rodents, including social recognition, object
recognition, object placement (spatial memory) and social learning. By comparing
studies utilising systemic or intracranial treatments, as well as pre- and post
acquisition administration of oestradiol or ER agonists, the respective
contributions of individual ERs within specific brain regions to various forms of
learning and memory can be determined. The first part of this review explores the
effects of systemic administration of 17beta-oestradiol and ER agonists on memory
when administered either pre- or post-acquisition. The second part not only
focuses on the effects of pre- and post-acquisition infusions of 17beta
oestradiol or ER agonists into the dorsal hippocampus on memory, but also
discusses the contributions of other brain regions, including the medial
amygdala, medial prefrontal cortex and paraventricular nucleus of the
hypothalamus. The cellular mechanisms mediating the rapid effects of 17beta
oestradiol on memory, including activation of intracellular signalling cascades
and epigenetic processes, are discussed. Finally, the review concludes by
comparing pre- and post-acquisition findings and effects of 17beta-oestradiol and
ER agonists in different brain regions.
PMID- 28489297
TI - The effect of low-temperature laundering and detergents on the survival of
Escherichia coli and Staphylococcus aureus on textiles used in healthcare
uniforms.
AB - AIMS: To determine the survival of Escherichia coli and Staphylococcus aureus on
cotton and polyester and the effectiveness of low-temperature laundering and
detergents on the removal of micro-organism from healthcare laundry. METHODS AND
RESULTS: Survival of E. coli and S. aureus on polyester or cotton was assessed
over 3 weeks and the efficacy of a domestic wash (40 and 60 degrees C) and a
range of detergents was also determined. Both bacteria were able to survive on
cotton (5 log(10) ) and polyester (0.28 log(10) ) for up to 3 weeks. Laundering
at 40 degrees C resulted in a 3.5 log(10) removal of the initial 7.7 log(10)
inoculum and some cross-contamination to sterile fabrics (3 log(10) ). Increasing
the temperature to 60 degrees C resulted in the complete removal of the initial
inoculum. CONCLUSIONS: This study shows that most of the micro-organisms are
removed at 40 degrees C, however, those cells still remaining may have the
potential for further contamination to the clinical environment and patients.
SIGNIFICANCE AND IMPACT OF THE STUDY: National Health Service (NHS) nurses are
required to domestically launder their uniforms at 60 degrees C to ensure safe
removal of micro-organisms, 33% of NHS staff questioned said they launder their
uniforms at 40 degrees C, which could potentially result in transmission of
hospital-acquired infections.
PMID- 28489299
TI - GP-patient communication about possible cancer in primary care: Re-evaluating GP
as gatekeeper.
AB - As possibilities for the early detection of indolent cancers, and precursors to
cancer, multiply, GPs will increasingly be involved in discussions with patients
about risks and benefits of early diagnosis and treatment. Over time,
improvements in evidence may decrease uncertainty about outcomes for patients and
clinicians. However, where survival benefits are small, or uncertain, or risks
are unacceptable to patients, grounds for preference-sensitive decision-making
will remain. How risks and benefits of early detection, and the significance of
indolent or low risk cancers, are communicated, will be key, if overtreatment and
overdiagnosis are to be avoided.
PMID- 28489298
TI - A randomized, double-blind, placebo-controlled clinical trial evaluating the role
of systemic antihistamine therapy for the reduction of adverse effects associated
with topical 5-aminolevulinic acid photodynamic therapy.
AB - BACKGROUND AND OBJECTIVE: Following photodynamic therapy with 5-aminolevulinic
acid (ALA-PDT), patients experience inflammation that may be partially
attributable to H1 histamine receptor activation. The objective of this study was
to evaluate the impact of antihistamines upon adverse effects following ALA-PDT.
STUDY DESIGN/MATERIALS AND METHODS: This was a randomized, placebo-controlled
clinical trial conducted at a single study site. Twenty subjects with facial
actinic keratoses were randomized to ALA-PDT plus cetirizine 10 mg (n = 10)
versus placebo daily (n = 10) from 3 days pre-treatment to 3 days post-treatment
for a total of 7 days. Signs of inflammation including erythema, edema, crusting,
exudation, vesiculation, and erosion were evaluated on post-treatment days 1, 2,
3, 7, 30, 90, and 180. Actinic keratosis counts, investigator-rated Global
Assessment Improvement Score (GAIS), healing, tolerability, and subject
satisfaction were also assessed. RESULTS: Erythema, edema, crusting, exudation,
vesiculation, and erosion were not different between treatment groups. Actinic
keratoses were significantly reduced by day 30 in both the antihistamine and
placebo groups (P = 0.01 and 0.0009, respectively), with results sustained to day
60 in the antihistamine group and day 180 for the placebo group. However, counts
were not different between groups at any time point. Investigator-rated GAIS,
subject satisfaction, healing, and tolerability were similar between treatment
groups. CONCLUSION: This study suggests that while H1 antihistamines do not
impair the efficacy of ALA-PDT, they also do not relieve post-treatment
inflammation and discomfort. Lasers Surg. Med. 49:738-742, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28489300
TI - Predictors of PTSD 40 years after combat: Findings from the National Vietnam
Veterans longitudinal study.
AB - BACKGROUND: Few studies have longitudinally examined predictors of posttraumatic
stress disorder (PTSD) in a nationally representative sample of US veterans. We
examined predictors of warzone-related PTSD over a 25-year span using data from
the National Vietnam Veterans Longitudinal Study (NVVLS). METHODS: The NVVLS is a
follow-up study of Vietnam theater veterans (N = 699) previously assessed in the
National Vietnam Veterans Readjustment Study (NVVRS), a large national
probability study conducted in the late 1980s. We examined the ability of 22
premilitary, warzone, and postmilitary variables to predict current warzone
related PTSD symptom severity and PTSD symptom change in male theater veterans
participating in the NVVLS. Data included a self-report Health Questionnaire
survey and a computer-assisted telephone Health Interview Survey. Primary
outcomes were self-reported PTSD symptoms assessed by the PTSD Checklist for DSM
5 (PCL 5) and Mississippi PTSD Scale (M-PTSD). RESULTS: Predictors of current
PTSD symptoms most robust in hierarchical multivariable models were African
American race, lower education level, negative homecoming reception, lower
current social support, and greater past-year stress. PTSD symptoms remained
largely stable over time, and symptom exacerbation was predicted by African
American race, lower education level, younger age at entry into Vietnam, greater
combat exposure, lower current social support, and greater past-year stressors.
CONCLUSIONS: Findings confirm the robustness of a select set of risk factors for
warzone-related PTSD, establishing that these factors can predict PTSD symptom
severity and symptom change up to 40 years postdeployment.
PMID- 28489301
TI - Hyperelastic Tough Gels through Macrocross-Linking.
AB - The wet and soft nature of hydrogels makes them useful as a mimic for biological
tissues, and in uses such as actuators and drug delivery vehicles. For many
applications the mechanical performance of the gel is critical, but gels are
notoriously weak and prone to fracture. Free radical polymerization is a very
powerful technique allowing for fine spatial and temporal control of
polymerization, but also allows for the use of a wide range of monomers and
mixtures. In this work, it is demonstrated that extremely tough and extensible
hydrogels can be readily produced through simple radical polymerization of
acrylamide or acrylic acid with a poly(ethylene oxide) macrocross-linker. These
gels, with a water content of 85%, are extremely elastic with an extension much
more than 15 000% at 9 MPa true stress. They can be compressed over 98% at a
stress of 17 MPa. They are notch-insensitive, and the usual trouser tear test
does not work because the tear simply does not propagate. This highly extensible
nature seems to be related to very long chain lengths between cross-links and
efficient incorporation of chains into the network.
PMID- 28489302
TI - Characterization of a furan aldehyde-tolerant beta-xylosidase/alpha-arabinosidase
obtained through a synthetic metagenomics approach.
AB - AIMS: The aim of the study was to characterize 10 hemicellulolytic enzymes
obtained from a wheat straw-degrading microbial consortium. METHODS AND RESULTS:
Based on previous metagenomics analyses, 10 glycosyl hydrolases were selected,
codon-optimized, synthetized, cloned and expressed in Escherichia coli. Nine of
the overexpressed recombinant proteins accumulated in cellular inclusion bodies,
whereas one, a 37.5-kDa protein encoded by gene xylM1989, was found in the
soluble fractions. The resulting protein, denoted XylM1989, showed beta
xylosidase and alpha-arabinosidase activities. It fell in the GH43 family and
resembled a Sphingobacterium sp. protein. The XylM1989 showed optimum activity at
20 degrees C and pH 8.0. Interestingly, it kept approximately 80% of its beta
xylosidase activity in the presence of 0.5% (w/v) furfural and 0.1% (w/v) 5
hydroxymethylfurfural. Additionally, the presence of Ca2+ , Mg2+ and Mn2+ ions
increased the enzymatic activity and conferred complete tolerance to 500 mmol l-1
of xylose. Protein XylM1989 is also able to release sugars from complex
polysaccharides. CONCLUSION: We report the characterization of a novel
bifunctional hemicellulolytic enzyme obtained through a targeted synthetic
metagenomics approach. SIGNIFICANCE AND IMPACT OF THE STUDY: The properties of
XylM1989 turn this protein into a promising enzyme that could be useful for the
efficient saccharification of plant biomass.
PMID- 28489304
TI - Infection of the fittest: devil facial tumour disease has greatest effect on
individuals with highest reproductive output.
AB - Emerging infectious diseases rarely affect all members of a population equally
and determining how individuals' susceptibility to infection is related to other
components of their fitness is critical to understanding disease impacts at a
population level and for predicting evolutionary trajectories. We introduce a
novel state-space model framework to investigate survival and fecundity of
Tasmanian devils (Sarcophilus harrisii) affected by a transmissible cancer, devil
facial tumour disease. We show that those devils that become host to tumours have
otherwise greater fitness, with higher survival and fecundity rates prior to
disease-induced death than non-host individuals that do not become infected,
although high tumour loads lead to high mortality. Our finding that individuals
with the greatest reproductive value are those most affected by the cancer
demonstrates the need to quantify both survival and fecundity in context of
disease progression for understanding the impact of disease on wildlife
populations.
PMID- 28489303
TI - N2 -to-NH3 Conversion by a triphos-Iron Catalyst and Enhanced Turnover under
Photolysis.
AB - Bridging iron hydrides are proposed to form at the active site of MoFe
nitrogenase during catalytic dinitrogen reduction to ammonia and may be key in
the binding and activation of N2 via reductive elimination of H2 . This
possibility inspires the investigation of well-defined molecular iron hydrides as
precursors for catalytic N2 -to-NH3 conversion. Herein, we describe the synthesis
and characterization of new P2P'Ph Fe(N2 )(H)x systems that are active for
catalytic N2 -to-NH3 conversion. Most interestingly, we show that the yields of
ammonia can be significantly increased if the catalysis is performed in the
presence of mercury lamp irradiation. Evidence is provided to suggest that photo
elimination of H2 is one means by which the enhanced activity may arise.
PMID- 28489306
TI - Pipecolic Acid Hydroxylases: A Monophyletic Clade among cis-Selective Bacterial
Proline Hydroxylases that Discriminates l-Proline.
AB - Proline hydroxylases are iron(II)/2-oxoglutarate-dependent enzymes that
hydroxylate l-proline and derivatives, such as lpipecolic acid, which is the six
membered-ring homologue of l-proline. It has been established that there is a
distinct group of conserved bacterial enzymes that hydroxylate l-pipecolic acid
and trans-3- and trans-4-methyl-l-proline, but virtually no l-proline. This
allows the organism to produce hydroxyproline congeners without hydroxylation of
the physiologically omnipresent l-proline. In vitro conversions showed that the
substrate spectrum of the pipecolic acid hydroxylases GetF (from a Streptomyces
sp.; producer of the tetrapeptide antibiotic GE81112) and PiFa (from Frankia
alni) overlaps that of proline hydroxylases, except for the nonacceptance of l
proline and smaller homologues. Distinct and conserved residues were determined
for both types of enzymes. However, site-directed mutagenesis in GetF did not
yield variants that accepted l-proline; this suggested a complex interaction of
several residues around the active site, which resulted in delicate changes in
substrate specificity. This is supported by substrate docking in a homology model
of GetF, which revealed an altered orientation for l-proline relative to that of
preferred substrates.
PMID- 28489305
TI - Prolonged Survival Following Pig-to-Primate Liver Xenotransplantation Utilizing
Exogenous Coagulation Factors and Costimulation Blockade.
AB - Since the first attempt of pig-to-primate liver xenotransplantation (LXT) in
1968, survival has been limited. We evaluated a model utilizing alpha-1,3
galactosyltransferase knockout donors, continuous posttransplant infusion of
human prothrombin concentrate complex, and immunosuppression including anti
thymocyte globulin, FK-506, methylprednisone, and costimulation blockade
(belatacept, n = 3 or anti-CD40 mAb, n = 1) to extend survival. Baboon 1 remained
well until postoperative day (POD) 25, when euthanasia was required because of
cholestasis and plantar ulcers. Baboon 2 was euthanized following a seizure on
POD 5, despite normal liver function tests (LFTs) and no apparent pathology.
Baboon 3 demonstrated initial stable liver function but was euthanized on POD 8
because of worsening LFTs. Pathology revealed C4d positivity, extensive
hemorrhagic necrosis, and a focal cytomegalovirus inclusion. Baboon 4 was
clinically well with stable LFTs until POD29, when euthanasia was again
necessitated by plantar ulcerations and rising LFTs. Final pathology was C4d
negative and without evidence of rejection, inflammation, or thrombotic
microangiopathy. Thus, nearly 1-mo rejection-free survival has been achieved
following LXT in two of four consecutive recipients, demonstrating that the
porcine liver can support life in primates for several weeks and has encouraging
potential for clinical application as a bridge to allotransplantation for
patients with acute-on-chronic or fulminant hepatic failure.
PMID- 28489307
TI - Non-alcoholic fatty liver and advanced fibrosis in the elderly: Results from a
community-based Polish survey.
AB - BACKGROUND & AIMS: Development of non-alcoholic fatty liver (NAFL) is dependent
on metabolic factors occurring at an increased frequency with advancing age.
Until now, few studies have explored the prevalence of NAFL in aged populations.
Our study aimed to determine the prevalence of NAFL and advanced fibrosis in the
elderly population participating in a national survey of a community-based
elderly cohort. METHODS: A total of 3003 participants (mean age 79.6 years, 46.8%
male) were enrolled in the study, after applying the following exclusion
criteria: individuals younger than 65 years old (n=829) and those with positive
serological biomarkers of HBV or HCV infection (n=391), chronic alcohol ingestion
(n=727) or incomplete data records (n=745). Based on the fatty liver index (FLI),
the participants were classified into three categories: FLI<30 (no NAFL),
30<=FLI<60 (borderline) and FLI>=60 (NAFL). According to the non-alcoholic fatty
liver disease (NAFLD) fibrosis score (NFS), the participants were divided into
three advanced fibrosis risk categories: NFS<-1.455 (low risk),
1.455<=NFS<=0.676 (intermediate risk) and NFS>0.676 (high risk). RESULTS: The
prevalence of NAFL in the general population was 37.2%; the prevalence reached
51.4% in participants 65-70 years of age and decreased with advancing age
(P<.0001). The prevalence of advanced fibrosis was 7.79% (14.8% in the NAFL
population) and increased with advancing age (P<.005). CONCLUSIONS: The
prevalence of NAFL and metabolically driven advanced fibrosis are relatively
common in the elderly population, and these hepatic conditions run in adverse
directions with advancing age.
PMID- 28489309
TI - Isotropic three-dimensional T2 mapping of knee cartilage: Development and
validation.
AB - PURPOSE: 1) To implement a higher-resolution isotropic 3D T2 mapping technique
that uses sequential T2 -prepared segmented gradient-recalled echo (Iso3DGRE)
images for knee cartilage evaluation, and 2) to validate it both in vitro and in
vivo in healthy volunteers and patients with knee osteoarthritis. MATERIALS AND
METHODS: The Iso3DGRE sequence with an isotropic 0.6 mm spatial resolution was
developed on a clinical 3T MR scanner. Numerical simulations were performed to
optimize the pulse sequence parameters. A phantom study was performed to validate
the T2 estimation accuracy. The repeatability of the sequence was assessed in
healthy volunteers (n = 7). T2 values were compared with those from a clinical
standard 2D multislice multiecho (MSME) T2 mapping sequence in knees of healthy
volunteers (n = 13) and in patients with knee osteoarthritis (OA, n = 5).
RESULTS: The numerical simulations resulted in 100 excitations per segment and an
optimal radiofrequency (RF) excitation angle of 15 degrees . The phantom study
demonstrated a good correlation of the technique with the reference standard
(slope 0.9 +/- 0.05, intercept 0.2 +/- 1.7 msec, R2 >= 0.99). Repeated
measurements of cartilage T2 values in healthy volunteers showed a coefficient of
variation of 5.6%. Both Iso3DGRE and MSME techniques found significantly higher
cartilage T2 values (P < 0.03) in OA patients. Iso3DGRE precision was equal to
that of the MSME T2 mapping in healthy volunteers, and significantly higher in OA
(P = 0.01). CONCLUSION: This study successfully demonstrated that high-resolution
isotropic 3D T2 mapping for knee cartilage characterization is feasible,
accurate, repeatable, and precise. The technique allows for multiplanar
reformatting and thus T2 quantification in any plane of interest. LEVEL OF
EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:362-371.
PMID- 28489308
TI - Terminal Parent Phosphanide and Phosphinidene Complexes of Zirconium(IV).
AB - The reaction of [Zr(TrenDMBS )(Cl)] [Zr1; TrenDMBS =N(CH2 CH2 NSiMe2 But )3 ]
with NaPH2 gave the terminal parent phosphanide complex [Zr(TrenDMBS )(PH2 )]
[Zr2; Zr-P=2.690(2) A]. Treatment of Zr2 with one equivalent of KCH2 C6 H5 and
two equivalents of benzo-15-crown-5 ether (B15C5) afforded an unprecedented
example (outside of matrix isolation) of a structurally authenticated transition
metal terminal parent phosphinidene complex [Zr(TrenDMBS )(PH)][K(B15C5)2 ] [Zr3;
Zr=P=2.472(2) A]. DFT calculations reveal a polarized-covalent Zr=P double bond,
with a Mayer bond order of 1.48, and together with IR spectroscopic data also
suggest an agostic-type Zr???HP interaction [?ZrPH =66.7 degrees ] which is
unexpectedly similar to that found in cryogenic, spectroscopically observed
phosphinidene species. Surprisingly, computational data suggest that the Zr=P
linkage is similarly polarized, and thus as covalent, as essentially
isostructural U=P and Th=P analogues.
PMID- 28489311
TI - How do we measure childhood?
PMID- 28489312
TI - Blowing the whistle: moral distress and advocacy for preterm infants and their
families.
PMID- 28489313
TI - In utero seizures revealing dentato-olivary dysplasia caused by SCN2A mutation.
PMID- 28489314
TI - Unclassifiable pattern of hypopigmentation in a patient with mosaic partial 12p
tetrasomy without Pallister-Killian syndrome.
AB - Pallister-Killian syndrome (PKS-#OMIM601803) is a multisystem developmental
disorder typically due to the presence of an aneuploidy cell line, consisting of
a supernumerary tetrasomic chromosomal marker (SCM) arisen from the short arm of
chromosome 12 (12p isochromosome). The clinical phenotype, which is strictly
related to the percentage and tissue distribution of aneuploid cells, is
characterized by craniofacial dysmorphisms, pigmentary skin anomalies, limb
shortening, congenital heart defects, diaphragmatic hernia, hypotonia,
intellectual disability, and epilepsy. We report on a 4 year-old girl harboring a
12p partial isochromosome, involving the PKS critical region, affecting about 70%
of circulating lymphocytes, urine, and saliva cells and fibroblast from a
hyperpigmented skin spot, and 100% of fibroblasts from a hypopigmented skin spot.
Interestingly, despite the high proportion of affected cells this patient did not
present with PKS, and a pattern of linear and patchy pigmentary mosaicism was the
sole clinical manifestation. The present observation suggests that partial 12p
SCM can also result in mild phenotypes, and its prevalence in the human
population could have been underestimated. Accurate dermatologic evaluation could
be a major handle for genetic testing.
PMID- 28489315
TI - Mechanically-Guided Deterministic Assembly of 3D Mesostructures Assisted by
Residual Stresses.
AB - Formation of 3D mesostructures in advanced functional materials is of growing
interest due to the widespread envisioned applications of devices that exploit 3D
architectures. Mechanically guided assembly based on compressive buckling of 2D
precursors represents a promising method, with applicability to a diverse set of
geometries and materials, including inorganic semiconductors, metals, polymers,
and their heterogeneous combinations. This paper introduces ideas that extend the
levels of control and the range of 3D layouts that are achievable in this manner.
Here, thin, patterned layers with well-defined residual stresses influence the
process of 2D to 3D geometric transformation. Systematic studies through combined
analytical modeling, numerical simulations, and experimental observations
demonstrate the effectiveness of the proposed strategy through ~20 example cases
with a broad range of complex 3D topologies. The results elucidate the ability of
these stressed layers to alter the energy landscape associated with the
transformation process and, specifically, the energy barriers that separate
different stable modes in the final 3D configurations. A demonstration in a
mechanically tunable microbalance illustrates the utility of these ideas in a
simple structure designed for mass measurement.
PMID- 28489316
TI - Streptomyces: An annotated selection of World Wide Web sites relevant to the
topics in environmental microbiology.
PMID- 28489317
TI - Pharmacogenomics of angiotensin receptor/neprilysin inhibitor and its long-term
side effects.
AB - The development of the promising agent sacubitril/valsartan, known as an
angiotensin receptor blocker-neprilysin inhibitor (ARNI), to improve heart
failure (HF) management, may benefit morbidity, mortality, and readmission rates
in patients with HF. The PARADIGM-HF trial demonstrated that the ARNI can reduce
morbidity and mortality in patients with heart failure with reduced ejection
fraction (HFrEF), while ongoing PARAMOUNT and PARAGON-HF trials determined
whether the ARNI has morbidity and mortality benefits in patients with heart
failure with preserved ejection fraction (HFpEF). However, the risk of long-term
side effects of the ARNI such as cognitive dysfunction or Alzheimer's disease
(AD) remains unknown. In fact, neprilysin (NEP), encoded by NEP or MME gene, is a
principal peptidase involved in the degradation of beta-amyloid (Abeta) protein.
Several studies have demonstrated that polymorphisms of the NEP gene may be
associated with AD and cerebral amyloid angiopathy (CAA). Pharmacogenomics, the
study of variability in drug response due to genetic polymorphisms, can
potentially explain the variability in the effect of the ARNI and their side
effects. Therefore, we have attempted to highlight pharmacogenomic factors and
potential long-term side effects of the ARNI. Physicians should carefully monitor
elderly patients with genetic risk factors for AD and CAA. In the future, genetic
testing and genomic testing for NEP polymorphisms may play an important role in
monitoring long-term side effects in ARNI-treated HF patients.
PMID- 28489318
TI - Janus Copper Mesh Film with Unidirectional Water Transportation Ability toward
High Efficiency Oil/Water Separation.
AB - Inspired by the special asymmetric wettability and controllable permeation
function of cell membranes, we report a Janus nanostructured copper mesh film
with unidirectional water transportation ability. Water can permeate from the
hydrophobic side to the hydrophilic side, but is retained in the opposite
direction. Notably, based on this special unidirectional water permeation
property, both heavy oil/water mixtures (rhooil >rhowater ) and light oil/water
mixtures (rhooil 5
(15.1 vs. 2.7% expected; relative risk = 6.99, P < .001); the prevalence of
depressive symptoms was significantly lower in the other clusters (all P < .01).
The potential high-risk cluster had significant overrepresentations of obese
individuals (39.7 vs. 17.4% expected) and those with type 2 diabetes (24.7 vs.
8.5% expected), and underrepresentation of individuals who fulfilled the World
Health Organization's PA recommendations (15.6 vs. 59.1% expected; all P < .01),
as well as low levels of functional performance. CONCLUSIONS: The present study
provided a potential high-risk profile for depressive symptoms among elderly
community-dwelling individuals, which included low levels functional performance
combined with low levels of PA. Including PA in medical screening of the elderly
may aid in identification of potential high-risk individuals for depressive
symptoms.
PMID- 28489320
TI - Role of cyclooxygenase in the vascular responses to extremity cooling in
Caucasian and African males.
AB - NEW FINDINGS: What is the central question of this study? Compared with
Caucasians, African individuals are more susceptible to non-freezing cold injury
and experience greater cutaneous vasoconstriction and cooler finger skin
temperatures upon hand cooling. We investigated whether the enzyme cyclooxygenase
is, in part, responsible for the exaggerated response to local cooling. What is
the main finding and its importance? During local hand cooling, individuals of
African descent experienced significantly lower finger skin blood flow and skin
temperature compared with Caucasians irrespective of cyclooxygenase inhibition.
These data suggest that in young African males the cyclooxygenase pathway appears
not to be the primary reason for the increased susceptibility to non-freezing
cold injury. Individuals of African descent (AFD) are more susceptible to non
freezing cold injury (NFCI) and experience an exaggerated cutaneous
vasoconstrictor response to hand cooling compared with Caucasians (CAU). Using a
placebo-controlled, cross-over design, this study tested the hypothesis that
cyclooxygenase (COX) may, in part, be responsible for the exaggerated
vasoconstrictor response to local cooling in AFD. Twelve AFD and 12 CAU young
healthy men completed foot cooling and hand cooling (separately, in 8 degrees C
water for 30 min) with spontaneous rewarming in 30 degrees C air after placebo or
aspirin (COX inhibition) treatment. Skin blood flow, expressed as cutaneous
vascular conductance (as flux per millimetre of mercury), and skin temperature
were measured throughout. Irrespective of COX inhibition, the responses to foot
cooling, but not hand cooling, were similar between ethnicities. Specifically,
during hand cooling after placebo, AFD experienced a lower minimal skin blood
flow [mean (SD): 0.5 (0.1) versus 0.8 (0.2) flux mmHg-1 , P < 0.001] and a lower
minimal finger skin temperature [9.5 (1.4) versus 10.7 (1.3) degrees C, P =
0.039] compared with CAU. During spontaneous rewarming, average skin blood flow
was also lower in AFD than in CAU [2.8 (1.6) versus 4.3 (1.0) flux mmHg-1 , P <
0.001]. These data provide further support that AFD experience an exaggerated
response to hand cooling on reflection this appears to overstate findings;
however, the results demonstrate that the COX pathway is not the primary reason
for the exaggerated responses in AFD and increased susceptibility to NFCI.
PMID- 28489321
TI - Nicotine deprivation attenuates panic reactivity in smokers: Findings from a
placebo-controlled nicotine patch study.
AB - BACKGROUND: Prospective studies consistently find that smoking is a risk factor
for the development of panic disorder (PD). A possible explanation is that
nicotine deprivation promotes heightened sensitivity to bodily sensations and/or
arterial carbon dioxide (CO2 ). Abrams et al. (2011) previously found that, in
response to a CO2 rebreathing challenge, smokers experiencing more (vs. less)
intense nicotine withdrawal had more severe panic symptoms and a stronger urge to
escape. However, participants were aware of the last time they smoked, leaving
unclear the extent to which fear reactivity was influenced by the pharmacologic
effects of nicotine deprivation versus beliefs regarding when nicotine was most
recently used. The present study aimed to ascertain whether nicotine deprivation,
independent of beliefs regarding recent nicotine use, promotes fear reactivity
among smokers. METHODS: Moderate to heavy smokers without PD (N = 25)
participated in a placebo-controlled, double-blind study consisting of two
sessions spaced 1 week apart. Participants abstained from nicotine for 2 hr prior
to sessions. During one session participants were given a 21 mg nicotine
replacement patch and, during the other, a placebo patch, with the order
counterbalanced. For both sessions, after a 3-hr absorption period, participants
underwent a 10-min CO2 rebreathing challenge. RESULTS: Wearing a nicotine (vs.
placebo) patch increased self-reported panic reactivity among participants, but
did not significantly affect physiological and behavioral measures of reactivity.
CONCLUSIONS: In smokers without a history of PD, nicotine deprivation attenuates
subjective panic reactivity. Possible explanations for the contrast between
theory and laboratory findings as well as clinical implications are discussed.
PMID- 28489322
TI - Developmental effects of androgens in the human brain.
AB - Neuroendocrine theories of brain development posit that androgens play a crucial
role in sex-specific cortical growth, although little is known about the
differential effects of testosterone and dehydroepiandrosterone (DHEA) on cortico
limbic development and cognition during adolescence. In this context, the
National Institutes of Health Study of Normal Brain Development, a longitudinal
study of typically developing children and adolescents aged 4-24 years (n=433),
offers a unique opportunity to examine the developmental effects of androgens on
cortico-limbic maturation and cognition. Using data from this sample, our group
found that higher testosterone levels were associated with left-sided decreases
in cortical thickness (CTh) in post-pubertal boys, particularly in the prefrontal
cortex, compared to right-sided increases in CTh in somatosensory areas in pre
pubertal girls. Prefrontal-amygdala and prefrontal-hippocampal structural
covariance (considered to reflect structural connectivity) also varied according
to testosterone levels, with the testosterone-related brain phenotype predicting
higher aggression levels and lower executive function, particularly in boys. By
contrast, DHEA was associated with a pre-pubertal increase in CTh of several
regions involved in cognitive control in both boys and girls. Covariance within
several cortico-amygdalar structural networks also varied as a function of DHEA
levels, with the DHEA-related brain phenotype predicting improvements in visual
attention in both boys and girls. DHEA-related cortico-hippocampal structural
covariance, on the other hand, predicted higher scores on a test of working
memory. Interestingly, there were significant interactions between testosterone
and DHEA, such that DHEA tended to mitigate the anti-proliferative effects of
testosterone on brain structure. In sum, testosterone-related effects on the
developing brain may lead to detrimental effects on cortical functions (ie,
higher aggression and lower executive function), whereas DHEA-related effects may
optimise cortical functions (ie, better attention and working memory), perhaps by
decreasing the influence of amygdalar and hippocampal afferents on cortical
functions.
PMID- 28489324
TI - Executive summary of the SCAI/HFSA clinical expert consensus document on the use
of invasive hemodynamics for the diagnosis and management of cardiovascular
disease.
PMID- 28489323
TI - Mild, moderate, meaningful? Examining the psychological and functioning
correlates of DSM-5 eating disorder severity specifiers.
AB - OBJECTIVE: This study evaluated the DSM-5 severity specifiers for treatment
seeking groups of participants with anorexia nervosa (AN), the purging form of
bulimia nervosa (BN), and binge-eating disorder (BED). METHOD: Hundred and sixty
two participants with AN, 93 participants with BN, and 343 participants with BED
were diagnosed using semi-structured interviews, sub-categorized using DSM-5
severity specifiers and compared on demographic and cross-sectional clinical
measures. RESULTS: In AN, the number of previous hospitalizations and the
duration of illness increased with severity, but there was no difference across
severity groups on measures of eating pathology, depression, or measures of self
reported physical or emotional functioning. In BN, the level of eating concerns
increased across the severity groups, but the groups did not differ on measures
of depression, self-esteem, and most eating pathology variables. In BN, support
was also found for an alternative severity classification scheme based upon
number of methods of purging. In BED, levels of several measures of eating
pathology and self-reported physical and emotional functioning increased across
the severity groups. For BED, however, support was also found for an alternative
severity classification scheme based upon overvaluation of shape and weight.
Preliminary evidence was also found for a transdiagnostic severity index based
upon overvaluation of shape and weight. DISCUSSION: Overall, these data show
limited support for the DSM-5 severity specifiers for BN and modest support for
the DSM-5 severity specifiers for AN and BED.
PMID- 28489325
TI - Reducing Macro- and Microheterogeneity of N-Glycans Enables the Crystal Structure
of the Lectin and EGF-Like Domains of Human L-Selectin To Be Solved at 1.9 A
Resolution.
AB - L-Selectin, a cell-adhesion receptor on the surface of most leukocytes, contains
seven N-glycosylation sites. In order to obtain the crystal structure of human L
selectin, we expressed a shortened version of L-selectin comprising the C-type
lectin and EGF-like domains (termed LE) and systematically analysed mutations of
the three glycosylation sites (Asn22, Asn66 and Asn139) in order to reduce
macroheterogeneity. After we further removed microheterogeneity, we obtained
crystals that diffracted X-rays up to 1.9 A from a variant (LE010) with exchanges
N22Q and N139Q and one GlcNAc2 Man5 N-glycan chain attached to Asn66. Crystal
structure analysis showed that the terminal mannose of GlcNAc2 Man5 of one LE010
molecule was coordinated to Ca2+ in the binding site of a symmetry-related LE010.
The orientation of the lectin and EGF-like domain was similar to the described
"bent" conformation of E- and P-selectins. The Ca2+ -binding site reflects the
binding mode seen in E- and P-selectin structures co-crystallised with ligands.
PMID- 28489326
TI - Highly Selective Stable Isotope Labeling of Histidine Residues by Using a Novel
Precursor in E. coli-Based Overexpression Systems.
AB - The importance of NMR spectroscopy in unraveling the structural and dynamic
properties of proteins is ever-expanding owing to progress in experimental
techniques, hardware development, and novel labeling approaches. Multiple
sophisticated methods of aliphatic residue labeling can be found in the
literature, whereas the selective incorporation of NMR active isotopes into other
amino acids still holds the potential for improvement. In order to close this
methodological gap, we present a novel metabolic precursor for cell-based protein
overexpression to assemble 13 C/2 H isotope patterns in the peptide backbone, as
well as in side chain positions of a mechanistically distinguished histidine
residue.
PMID- 28489328
TI - Induction of Chondrogenic Differentiation of Human Mesenchymal Stem Cells by
Biomimetic Gold Nanoparticles with Tunable RGD Density.
AB - Nanostructured materials have drawn a broad attention for their applications in
biomedical fields. Ligand-modified nanomaterials can well mimic the dynamic
extracellular matrix (ECM) microenvironments to regulate cell functions and
fates. Herein, ECM mimetic gold nanoparticles (Au NPs) with tunable surface
arginine-glycine-aspartate (RGD) density are designed and synthesized to induce
the chondrogenic differentiation of human mesenchymal stem cells (hMSCs). The
biomimetic Au NPs with an average size of 40 nm shows good biocompatibility
without affecting the cell proliferation in the studied concentration range. The
RGD motifs on Au NPs surface facilitate cellular uptake of NPs into monolayer
hMSCs through integrin-mediated endocytosis. The biomimetic NPs have a promotive
effect on cartilaginous matrix production and marker gene expression in cell
pellet culture, especially for the biomimetic Au NPs with high surface RGD
density. This study provides a novel strategy for fabricating biomimetic NPs to
regulate cell differentiation, which holds great potentials in tissue engineering
and biomedical applications.
PMID- 28489327
TI - New directions for the treatment of depression: Targeting the photic regulation
of arousal and mood (PRAM) pathway.
AB - Both preclinical and clinical studies demonstrate that depression is strongly
associated with reduced light availability, which in turn contributes to
decreased function of brain regions that control mood. Here, we review findings
that support a critical pathway for the control of mood that depends upon ambient
light. We put forward a novel hypothesis, functionally linking retina to locus
coeruleus (LC) in depression, and discuss the role of norepinephrine in affective
disease. Finally, we discuss how utilizing the chemogenetic tool Designer
Receptors Exclusively Activated by Designer Drugs (DREADDs) to precisely control
this retina-LC circuit may be used as a novel therapeutic to treat depression.
PMID- 28489329
TI - Differential responses of soil bacteria, fungi, archaea and protists to plant
species richness and plant functional group identity.
AB - Plants are known to influence belowground microbial community structure along
their roots, but the impacts of plant species richness and plant functional group
(FG) identity on microbial communities in the bulk soil are still not well
understood. Here, we used 454-pyrosequencing to analyse the soil microbial
community composition in a long-term biodiversity experiment at Jena, Germany. We
examined responses of bacteria, fungi, archaea, and protists to plant species
richness (communities varying from 1 to 60 sown species) and plant FG identity
(grasses, legumes, small herbs, tall herbs) in bulk soil. We hypothesized that
plant species richness and FG identity would alter microbial community
composition and have a positive impact on microbial species richness. Plant
species richness had a marginal positive effect on the richness of fungi, but we
observed no such effect on bacteria, archaea and protists. Plant species richness
also did not have a large impact on microbial community composition. Rather,
abiotic soil properties partially explained the community composition of
bacteria, fungi, arbuscular mycorrhizal fungi (AMF), archaea and protists. Plant
FG richness did not impact microbial community composition; however, plant FG
identity was more effective. Bacterial richness was highest in legume plots and
lowest in small herb plots, and AMF and archaeal community composition in legume
plant communities was distinct from that in communities composed of other plant
FGs. We conclude that soil microbial community composition in bulk soil is
influenced more by changes in plant FG composition and abiotic soil properties,
than by changes in plant species richness per se.
PMID- 28489330
TI - Comment on "Flexible Asymmetric Supercapacitors Based on Nitrogen-Doped Graphene
Hydrogels with Embedded Nickel Hydroxide Nanoplates".
AB - It is argued that the main claims of "Flexible Asymmetric Supercapacitors Based
on Nitrogen-Doped Graphene Hydrogels with Embedded Nickel Hydroxide Nanoplates"
are strongly exaggerated. By selecting first a subregion (DeltaV) of the total
voltage drop, the capacitance (CDeltaV ) is inflated by 30 %. Then, by selecting
different regions for different properties and using different DeltaV values in
different terms of a single expression for the energy density (EDeltaV ), the
value is doubled. A bending angle of only 45 degrees is instead claimed to be
180 degrees .
PMID- 28489331
TI - SCAI/HFSA clinical expert consensus document on the use of invasive hemodynamics
for the diagnosis and management of cardiovascular disease.
PMID- 28489332
TI - Damage, Healing, and Remodeling in Optogenetic Skeletal Muscle Bioactuators.
AB - A deeper understanding of biological materials and the design principles that
govern them, combined with the enabling technology of 3D printing, has given rise
to the idea of "building with biology." Using these materials and tools, bio
hybrid robots or bio-bots, which adaptively sense and respond to their
environment, can be manufactured. Skeletal muscle bioactuators are developed to
power these bio-bots, and an approach is presented to make them dynamically
responsive to changing environmental loads and robustly resilient to induced
damage. Specifically, since the predominant cause of skeletal muscle loss of
function is mechanical damage, the underlying mechanisms of damage are
investigated in vitro, and an in vivo inspired healing strategy is developed to
counteract this damage. The protocol that is developed yields complete recovery
of healthy tissue functionality within two days of damage, setting the stage for
a more robust, resilient, and adaptive bioactuator technology than previously
demonstrated. Understanding and exploiting the adaptive response behaviors
inherent within biological systems in this manner is a crucial step forward in
designing bio-hybrid machines that are broadly applicable to grand engineering
challenges.
PMID- 28489333
TI - Highly Efficient and Uniform 1 cm2 Perovskite Solar Cells with an
Electrochemically Deposited NiOx Hole-Extraction Layer.
AB - Given that the highest certified conversion efficiency of the organic-inorganic
perovskite solar cell (PSC) already exceeds 22 %, which is even higher than that
of the polycrystalline silicon solar cell, the significance of new scalable
processes that can be utilized for preparing large-area devices and their
commercialization is rapidly increasing. From this perspective, the
electrodeposition method is one of the most suitable processes for preparing
large-area devices because it is an already commercialized process with proven
controllability and scalability. Here, a highly uniform NiOx layer prepared by
electrochemical deposition is reported as an efficient hole-extraction layer of a
p-i-n-type planar PSC with a large active area of >1 cm2 . It is demonstrated
that the increased surface roughness of the NiOx layer, achieved by controlling
the deposition current density, facilitates the hole extraction at the interface
between perovskite and NiOx , and thus increases the fill factor and the
conversion efficiency. The electrochemically deposited NiOx layer also exhibits
extremely uniform thickness and morphology, leading to highly efficient and
uniform large-area PSCs. As a result, the p-i-n-type planar PSC with an area of
1.084 cm2 exhibits a stable conversion efficiency of 17.0 % (19.2 % for 0.1 cm2 )
without showing hysteresis effects.
PMID- 28489334
TI - Diagnosis of CoPAN by whole exome sequencing: Waking up a sleeping tiger's eye.
AB - Neurodegeneration with brain iron accumulation (NBIA) is a group of
neurodegenerative disorders characterized by iron accumulation in the basal
ganglia. Recently, mutations in CoA synthase (COASY) have been identified as a
cause of a novel NBIA subtype (COASY Protein-Associated Neurodegeneration, CoPAN)
in two patients with dystonic paraparesis, parkinsonian features, cognitive
impairment, behavior abnormalities, and axonal neuropathy. COASY encodes an
enzyme required for Coenzyme A (CoA) biosynthesis. Using whole exome sequencing
(WES) we identified compound heterozygous COASY mutations in two siblings with
intellectual disability, ataxic gait, progressive spasticity, and obsessive
compulsive behavior. The "eye-of-the tiger-sign," a characteristic hypointense
spot within the hyperintense globi pallidi on MRI found in the most common
subtype of NBIA (Pantothenate Kinase-Associated Neurodegeneration, PKAN), was not
present. Instead, bilateral hyperintensity and swelling of caudate nucleus,
putamen, and thalamus were found. In addition, our patients showed a small corpus
callosum and frontotemporal and parietal white matter changes, expanding the
brain phenotype of patients with CoPAN. Metabolic investigations showed increased
free carnitine and decreased acylcarnitines in the patients dried blood samples.
Carnitine palmitoyl transferase 1 (CPT1) deficiency was excluded by further
enzymatic and metabolic investigations. As CoA and its derivate Acetyl-CoA play
an essential role in fatty acid metabolism, we assume that abnormal acylcarnitine
profiles are a result of the COASY mutations. This report not only illustrates
that WES is a powerful tool to elucidate the etiology of rare genetic diseases,
but also identifies unique neuroimaging and metabolic findings that may be key
features for an early diagnosis of CoPAN.
PMID- 28489335
TI - Phacomatosis pigmentokeratotica and precocious puberty associated with HRAS
mutation.
PMID- 28489336
TI - Antimicrobial activity of natural products against Clostridium difficile in
vitro.
AB - AIMS: To investigate the antimicrobial activity of various natural products
against Clostridium difficile in vitro. METHODS AND RESULTS: The antibacterial
activity of 20 natural products was determined by the agar well diffusion and
broth microdilution assays against four C. difficile strains, three comparator
organisms and four gastrointestinal commensal organisms. Of the raw natural
products, garlic juice had the highest activity. The most active processed
products were peppermint oil and the four pure compounds trans-cinnamaldehyde,
allicin, menthol and zingerone. Furthermore, Bacteroides species had similar
susceptibility to C. difficile to most natural products; however, Lactobacillus
casei was less susceptible. The combined effect of natural products with
vancomycin or metronidazole was determined using the conventional checkerboard
titration method and the fractional inhibitory concentration index was
calculated. The results showed a possible synergism between trans-cinnamaldehyde
and vancomycin and partial synergy between trans-cinnamaldehyde and
metronidazole. CONCLUSIONS: The study indicates a range of antimicrobial activity
of natural products against C. difficile and suggests that they may be useful as
alternative or complementary treatments for C. difficile infection (CDI),
particularly as most are able to be given orally. SIGNIFICANCE AND IMPACT OF THE
STUDY: This study encourages further investigation of natural products for
treatment of CDI.
PMID- 28489337
TI - Quality of randomized controlled trials in eating disorder prevention.
AB - OBJECTIVE: To investigate the quality of randomized controlled trials (RCTs) of
eating disorder prevention. METHOD: A systematic literature search was conducted
in Medline, PsycINFO, Embase, Scopus, and the Cochrane Collaboration Library to
January 2016. Studies were included if they were RCTs that tested an eating
disorder prevention program. We identified 96 studies with a total 15,350
participants (91% female, M age = 17 years) and rated quality with the Quality
Rating Scale (QRS; Moncrieff et al., 2001). RESULTS: The mean QRS score was 62%
(SD = 13%). Several standards of quality were not frequently fulfilled (i.e.,
failed to achieve an optimal rating), for example, power calculation (85%),
intent-to-treat analysis (54%), blinding of assessor (75%), representative sample
(78%), adequate sample size (75%), and appropriate duration of trial including
follow-up (67%). QRS was positively and significantly associated with publication
year, number of authors, and PubMed-indexation. DISCUSSION: Given the majority of
eating disorder prevention studies had problems with trial quality, it is
recommended that future RCTs follow quality checklists and CONSORT guidelines,
that RCTs are registered, and protocols published in advance. In addition,
funding bodies are called on to deliver the support needed to ensure that
preventions for eating disorders are efficiently and cost-effectively achieved.
PMID- 28489338
TI - Regulatory T Cells Promote Natural Killer Cell Education in Mixed Chimeras.
AB - Therapeutic administration of regulatory T cells (Tregs) leads to engraftment of
conventional doses of allogeneic bone marrow (BM) in nonirradiated recipient mice
conditioned with costimulation blockade and mammalian target of rapamycin
inhibition. The mode of action responsible for this Treg effect is poorly
understood but may encompass the control of costimulation blockade-resistant
natural killer (NK) cells. We show that transient NK cell depletion at the time
of BM transplantation led to BM engraftment and persistent chimerism without Treg
transfer but failed to induce skin graft tolerance. In contrast, the permanent
absence of anti-donor NK reactivity in mice grafted with F1 BM was associated
with both chimerism and tolerance comparable to Treg therapy, implying that NK
cell tolerization is a critical mechanism of Treg therapy. Indeed, NK cells of
Treg-treated BM recipients reshaped their receptor repertoire in the presence of
donor MHC in a manner suggesting attenuated donor reactivity. These results
indicate that adoptively transferred Tregs prevent BM rejection, at least in
part, by suppressing NK cells and promote tolerance by regulating the appearance
of NK cells expressing activating receptors to donor class I MHC.
PMID- 28489339
TI - De novo IGF2 mutation on the paternal allele in a patient with Silver-Russell
syndrome and ectrodactyly.
AB - Although paternally expressed IGF2 is known to play a critical role in placental
and body growth, only a single mutation has been found in IGF2. We identified,
through whole-exome sequencing, a de novo IGF2 indel mutation leading to
frameshift (NM_000612.5:c.110_117delinsAGGTAA, p.(Leu37Glnfs*31)) in a patient
with Silver-Russell syndrome, ectrodactyly, undermasculinized genitalia,
developmental delay, and placental hypoplasia. Furthermore, we demonstrated that
the mutation resided on the paternal allele by sequencing the long PCR product
harboring the mutation- and methylation-sensitive SmaI and SalI sites before and
after SmaI/SalI digestion. The results, together with the previous findings in
four cases from a single family with a paternally inherited IGF2 nonsense
mutation and those in patients with variable H19 differentially methylated region
epimutations leading to compromised IGF2 expression, suggest that the whole
phenotype of this patient is explainable by the IGF2 mutation, and that
phenotypic severity is primarily determined by the IGF2 expression level in
target tissues.
PMID- 28489340
TI - Comment: obesity as a disease - some implications for the World Obesity
Federation's advocacy and public health activities.
PMID- 28489342
TI - pH-Sensitive Reversible Programmed Targeting Strategy by the Self
Assembly/Disassembly of Gold Nanoparticles.
AB - A reversible programmed targeting strategy could achieve high tumor accumulation
due to its long blood circulation time and high cellular internalization. Here,
targeting ligand-modified poly(ethylene glycol) (PEG-ligand), dibutylamines (Bu),
and pyrrolidinamines (Py) were introduced on the surface of gold nanoparticles
(Au NPs) for reversible shielding/deshielding of the targeting ligands by pH
responsive self-assembly. Hydrophobic interaction and steric repulsion are the
main driving forces for the self-assembly/disassembly of Au NPs. The precise self
assembly (pH >= 7.2) and disassembly (pH <= 6.8) of Au NPs with different ligands
could be achieved by fine-tuning the modifying molar ratio of Bu and Py (Rm),
which followed the formula Rm = 1/(-0.0013X2 + 0.0323X + 1), in which X is the
logarithm of the partition coefficient of the targeting ligand. The
assembled/disassembled behavior of Au NPs at pH 7.2 and 6.8 was confirmed by
transmission electron microscopy and dynamic light scattering. Enzyme-linked
immunosorbent assays and cellular uptake studies showed that the ligands could be
buried inside the assembly and exposed when disassembled. More importantly, this
process was reversible, which provides the possibility of prolonging blood
circulation by shielding ligands associated with the NPs that were effused from
tumor tissue.
PMID- 28489341
TI - Smart Asymmetric Vesicles with Triggered Availability of Inner Cell-Penetrating
Shells for Specific Intracellular Drug Delivery.
AB - Smart nanocarriers attract considerable interest in the filed of precision
nanomedicine. Dynamic control of the interaction between nanocarriers and cells
offers the feasibility that in situ activates cellular internalization at the
targeting sites. Herein, we demonstrate a novel class of enzyme-responsive
asymmetric polymeric vesicles self-assembled from matrix metalloproteinase (MMP)
cleavable peptide-linked triblock copolymer, poly(ethylene glycol)-GPLGVRG-b
poly(epsilon-caprolactone)-b-poly(3-guanidinopropyl methacrylamide) (PEG-GPLGVRG
PCL-PGPMA), in which the cell-penetrating PGPMA segments asymmetrically
distribute in the outer and inner shells with fractions of 9% and 91%,
respectively. Upon treatment with MMP-2 to cleave the stealthy PEG shell, the
vesicles undergo morphological transformation into fused multicavity vesicles and
small nanoparticles, accompanied by redistribution of PGPMA segments with 76%
exposed to the outside. The vesicles after dePEGylation show significantly
increased cellular internalization efficiency (~10 times) as compared to the
original ones due to the triggered availability of cell-penetrating shells. The
vesicles loading hydrophobic anticancer drug paclitaxel (PTX) in the membrane
exhibit significantly enhanced cytotoxicity against MMP-overexpressing HT1080
cells and multicellular spheroids. The proposed vesicular system can serve as a
smart nanoplatform for in situ activating intracellular drug delivery in MMP
enriched tumors.
PMID- 28489343
TI - Rearranged Biosynthetic Gene Cluster and Synthesis of Hassallidin E in
Planktothrix serta PCC 8927.
AB - Cyanobacteria produce a wide range of natural products with antifungal
bioactivity. The cyclic glycosylated lipopeptides of the hassallidin family have
potent antifungal activity and display a great degree of chemical diversity.
Here, we report the discovery of a hassallidin biosynthetic gene cluster from the
filamentous cyanobacterium Planktothrix serta PCC 8927. The hassallidin gene
cluster showed heavy rearrangement and marks of genomic plasticity. Nucleotide
bias, differences in GC content, and phylogenetic incongruence suggested the
acquisition of the hassallidin biosynthetic gene cluster in Planktothrix serta
PCC 8927 by horizontal gene transfer. Chemical analyses by liquid chromatography
and mass spectrometry demonstrated that this strain produced hassallidin E, a new
glycosylated hassallidin variant. Hassallidin E was the only structural variant
produced by Planktothrix serta PCC 8927 in all tested conditions. Further
evaluated on human pathogenic fungi, hassallidin E showed an antifungal
bioactivity. Hassallidin production levels correlated with nitrogen availability,
in the only nitrogen-fixing Planktothrix described so far. Our results provide
insights into the distribution and chemical diversity of cyanobacterial
antifungal compounds as well as raise questions on their ecological relevance.
PMID- 28489344
TI - In Situ Engineering Toward Core Regions: A Smart Way to Make Applicable
FeF3@Carbon Nanoreactor Cathodes for Li-Ion Batteries.
AB - Iron fluorides (FeFx) have attracted great interest in Li-ion batteries due to
their high theoretical capacity, low cost, and preferable cell safety. However,
their practical utilization is severely impeded by inferior electrode kinetics,
leading to poor electrode cyclability and rate capabilities. The major bottleneck
should be lack of any effective engineering techniques to make reliable
encapsulation and conducting matrix on soluble FeFx species. Herein, we propose
an applicable synthetic strategy where the massive production of FeF3@carbon
nanoreactors (total size: ~60 nm) can be easily achieved by in situ engineering
toward the core regions in hybrids, with the iron rust wastes and common solvents
as raw materials. Such functionalized configurations can well make up for the
shortcomings of FeF3 species, enabling them with outstanding cathode behaviors
involving excellent reversible capacity retention (~270% higher than that of a
bare FeF3 electrode after 600 cycles) and drastically enhanced rate performance.
This paradigm work provides a facile and scalable method to make superior and
sustainable cathodes and, moreover, offers a feasible engineering protocol to
make water-soluble species encapsulated into carbon matrix, not merely for
batteries but also for other wide range of fields like catalysis, nanomedicine,
etc.
PMID- 28489345
TI - Orthogonal Liquid Crystal Alignment Layer: Templating Speed-Dependent Orientation
of Chromonic Liquid Crystals.
AB - Lyotropic chromonic liquid crystals (LCLCs) have been extensively studied because
of the interesting structural characteristics of the linear aggregation of their
plank-shaped molecules in aqueous solvents. We report a simple method to control
the orientation of LCLCs such as Sunset Yellow (SSY), disodium cromoglycate
(DSCG), and DNA by varying pulling speed of the top substrate and temperatures
during shear flow induced experiment. Crystallized columns of LCLCs are aligned
parallel and perpendicular to the shear direction, at fast and slow pulling
speeds of the top substrate, respectively. On the basis of this result, we
fabricated an orthogonally patterned film that can be used as an alignment layer
for guiding rodlike liquid crystals (LCs) to generate both twisted and planar
alignments simultaneously. Our resulting platform can provide a facile method to
form multidirectional orientation of soft materials and biomaterials in a process
of simple shearing and evaporation, which gives rise to potential patterning
applications using LCLCs due to their unique structural characteristics.
PMID- 28489346
TI - Metal-Organic Frameworks at the Biointerface: Synthetic Strategies and
Applications.
AB - Many living organisms are capable of producing inorganic materials of precisely
controlled structure and morphology. This ubiquitous process is termed
biomineralization and is observed in nature from the macroscale (e.g., formation
of exoskeletons) down to the nanoscale (e.g., mineral storage and transportation
in proteins). Extensive research efforts have pursued replicating this chemistry
with the overarching aims of synthesizing new materials of unprecedented physical
properties and understanding the complex mechanisms that occur at the biological
inorganic interface. Recently, we demonstrated that a class of porous materials
termed metal-organic frameworks (MOFs) can spontaneously form on protein-based
hydrogels via a process analogous to natural matrix-mediated biomineralization.
Subsequently, this strategy was extended to functional biomacromolecules,
including proteins and DNA, which have been shown to seed and accelerate
crystallization of MOFs. Alternative strategies exploit co-precipitating agents
such as polymers to induce MOF particle formation thus facilitating protein
encapsulation within the porous crystals. In these examples the rigid molecular
architecture of the MOF was found to form a protective coating around the
biomacromolecule offering improved stability to external environments that would
normally lead to its degradation. In this way, the MOF shell mimics the
protective function of a biomineralized exoskeleton. Other methodologies have
also been explored to encapsulate enzymes within MOF structures, including the
fabrication of polycrystalline hollow MOF microcapsules that preserve the
original enzyme functionality over several batch reaction cycles. The potential
to design MOFs of varied pore size and chemical functionality has underpinned
studies describing the postsynthesis infiltration of enzymes into MOF pore
networks and bioconjugation strategies for the decoration of the MOF outer
surface, respectively. These methods and configurations allow for customized
biocomposites. MOF biocomposites have been extended from simple proteins to
complex biological systems including viruses, living yeast cells, and bacteria.
Indeed, a noteworthy result was that cells encapsulated within a crystalline MOF
shell remain viable after exposure to a medium containing lytic enzymes.
Furthermore, the cells can adsorb nutrients (glucose) through the MOF shell but
cease reproducing until the MOF casing is removed, at which point normal cellular
activity is fully restored. The field of MOF biocomposites is expansive and
rapidly developing toward different applied research fields including protection
and delivery of biopharmaceuticals, biosensing, biocatalysis, biobanking, and
cell and virus manipulation. This Account describes the current progress of MOFs
toward biotechnological applications highlighting the different strategies for
the preparation of biocomposites, the developmental milestones, the challenges,
and the potential impact of MOFs to the field.
PMID- 28489347
TI - Measurement of the Density of Engineered Silver Nanoparticles Using Centrifugal
FFF-TEM and Single Particle ICP-MS.
AB - A methodology has been developed to measure nanoparticle mass and density, by
combining centrifugal field-flow fractionation (CeFFF; more commonly called
sedimentation FFF or SdFFF) and transmission electron microscopy (TEM). Particle
effective mass obtained from CeFFF retention data and particle size obtained from
the TEM images were used to calculate the nanoparticle density. The method was
initially applied to measure the density of monodispersed polystyrene latex
nanoparticles. Measured densities for latex nanoparticles of 160-300 nm in
diameter were in the range of 1041-1063 kg m-3 with standard deviations of 0.6
1.1%. Densities of engineered silver nanoparticles with nominal diameters of 30,
60, 75, and 100 nm were measured using this methodology. For all four silver
nanoparticle samples, the measured densities were 18-24% lower than the nominal
density of metallic silver, with an overall mean value of 7900 +/- 675 kg m-3.
Density values calculated using nanoparticle mass values obtained from single
particle inductively coupled plasma-mass spectrometry (spICP-MS) measurements,
corroborated the CeFFF-TEM results. The difference in the density of the silver
nanoparticles compared to that of bulk silver suggests that the synthesis process
could impart 20-37% porosity in silver nanoparticles. The data has important
implications in the fields of nanomaterial, nanomedicine and nanotoxicology,
where assumption of the bulk density for nanoparticles can result in erroneous
estimation of parameters such as mass, size, porosity, and dosage. The presented
methodology provides a straightforward and reproducible means for measurement of
the density and porosity of engineered nanoparticles with a wide range of density
and size.
PMID- 28489348
TI - Novel Curcumin Liposome Modified with Hyaluronan Targeting CD44 Plays an Anti
Leukemic Role in Acute Myeloid Leukemia in Vitro and in Vivo.
AB - Curcumin has been widely used as a food additive for centuries and has been
recently explored for its anti-inflammatory and antitumor properties. Although
curcumin is pharmacologically safe and efficacious to certain cancers, its role
against acute myeloid leukemia (AML) still remains unclear, and it lacks clinical
application due to low water solubility and low in vivo bioavailability. To
address these issues, we developed a novel curcumin liposome modified with
hyaluronan (HA-Cur-LPs) to specifically deliver curcumin to AML by targeting CD44
on AML cell surface. When compared with free curcumin and nontargeted liposome
(Cur-LPs), the HA-Cur-LPs exhibited good stability, high affinity to CD44,
increased cellular uptake, and more potent activity on inhibiting AML cell
proliferation. The KG-1 cell implanted AML mice had significantly delayed, or
even prevented, AML progression following treatment with 50 mg/kg of curcumin
dose in the HA-Cur-LPs every 2 days for 2 weeks. Mechanistically, the anti-AML
effects of HA-Cur-LPs were achieved by inhibiting Akt/ERK pathways and activating
caspase-dependent apoptosis. Moreover, HA-Cur-LPs played a critical role in
downregulation of DNMT1 expression in AML, leading to DNA hypomethylation and
reactivation of tumor suppressor genes such as miR-223. The development and
assessment of the HA-Cur-LPs in this study provide another potential choice for
AML therapy, using HA-Cur-LPs as either a single treatment agent or in
combination with other treatments.
PMID- 28489349
TI - Wastewater for Urban Agriculture: A Significant Factor in Dissemination of
Antibiotic Resistance.
PMID- 28489350
TI - The Consequences of Nonrandomness in Species-Sensitivity in Relation to
Functional Traits for Ecosystem-Level Effects of Chemicals.
AB - Estimating ecosystem-level effects from single-species bioassays is a major
challenge in environmental risk assessment. Most extrapolation procedures are
based on the implicit assumption that species sensitivities are random with
regard to their functional traits. Here, we explore how nonrandomness in species
sensitivities affects how species-level and ecosystem level effects of chemical
exposure correspond. The effect of a correlation between the trait value under
control conditions and the sensitivity of the trait to chemical stress is studied
for two traits (per capita growth rate and monoculture yield) under constant and
temporary exposure. Theoretical model predictions are thereby validated against a
3-week microcosm experiment, in which eight marine diatoms systems with different
correlations between trait values and sensitivities were temporary (1 week) or
constantly (3 weeks) exposed to two concentrations of the herbicide atrazine (100
and 250 MUg L-1). Negative correlations increased the reduction in ecosystem
functioning (productivity) by atrazine for both traits. However, correlations in
the per capita growth rate affected productivity only shortly following changes
in environmental conditions, whereas correlations in the monoculture yield
affected productivity throughout exposure. Correlations between species
sensitivities and functional trait values can thus help to identify when
ecosystem-level effects are likely to exceed species-level effects.
PMID- 28489351
TI - Nickel-Catalyzed Reductive Dicarbofunctionalization of Alkenes.
AB - An intermolecular, three-component reductive dicarbofunctionalization of alkenes
is presented here. The combination of Ni catalysis with TDAE as final reductant
enables the direct formation of Csp3-Csp3 and Csp3-Csp2 bonds across a variety of
pi-systems using two different electrophiles that are sequentially activated with
exquisite selectivity under mild reaction conditions.
PMID- 28489352
TI - Molecular Characterization of Nitrogen-Containing Organic Compounds in Humic-like
Substances Emitted from Straw Residue Burning.
AB - The molecular composition of humic-like substances (HULIS) in different aerosol
samples was analyzed using an ultrahigh-resolution mass spectrometer to
investigate the influence of biomass burning on ambient aerosol composition.
HULIS in background aerosols were characterized with numerous molecular formulas
similar to biogenic secondary organic aerosols. The abundance of nitrogen
containing organic compounds (NOC), including nitrogen-containing bases (N-bases)
and nitroaromatics, increased dramatically in ambient aerosols affected by crop
residue burning in the farm field. The molecular distribution of N-bases in these
samples exhibited similar patterns to those observed in smoke particles freshly
emitted from lab-controlled burning of straw residues but were significantly
different with those observed from wood burning. Signal intensity of the major N
bases correlated well with the atmospheric concentrations of potassium and
levoglucosan. These N-bases can serve as molecular markers distinguishing HULIS
from crop residue burning with from wood burning. More nitroaromatics were
detected in ambient aerosols affected by straw burning than in fresh smoke
aerosols, indicating that many of them are formed in secondary oxidation
processes as smoke plumes evolve in the atmosphere. This study highlights the
significant contribution of crop residue burning to atmospheric NOC. Further
study is warranted to evaluate the roles of NOC on climate and human health.
PMID- 28489353
TI - Tailoring Thermoelectric Properties through Structure and Morphology in
Chemically Synthesized n-Type Bismuth Telluride Nanostructures.
AB - Here, we report a simple, cost-effective, surfactant-assisted, and aqueous-based
low-temperature reflux method for the synthesis of Bi2Te3 nanocrystals.
Thermoelectric properties of n-type bismuth telluride (BT) nanostructures are
reported by varying the morphology and crystal structure. Tuning the reaction
time from 1 to 36 h enables the phase transformation from BiTe with a hexagonal
crystal structure to Bi2Te3 with a rhombohedral crystal structure, which is
evident from the refined X-ray diffraction results and high-resolution
transmission electron microscopy analysis. A perfect stoichiometric balance is
achieved for all the compositions, and temperature variation of the electrical
resistivity of all BT nanostructures shows the typical metal to semiconducting
transition near room temperature. Seebeck coefficient and Hall measurements
confirm electrons as the majority carriers and show the typical characteristics
of n-type BT nanostructures. The nanocrystals inherited from the optimized
reaction conditions and high densification of nanoparticle interfaces contribute
to the considerable reduction of thermal conductivity in BT nanostructures.
Highly crystalline, uniformly distributed nanocrystals of Bi2Te3 formed for 24 h
reaction time demonstrate a promising figure of merit of 0.81 at 350 K, which can
be attributed to their low thermal conductivity while the high electrical
conductivity is maintained. Our research could provide new possibilities in low
temperature synthesis where structural, compositional, and morphological tuning
of BT nanostructures could promote practical thermoelectric applications near
room temperature.
PMID- 28489354
TI - A Biphilic Phosphetane Catalyzes N-N Bond-Forming Cadogan Heterocyclization via
PIII/PV?O Redox Cycling.
AB - A small-ring phosphacycle, 1,2,2,3,4,4-hexamethylphosphetane, is found to
catalyze deoxygenative N-N bond-forming Cadogan heterocyclization of o
nitrobenzaldimines, o-nitroazobenzenes, and related substrates in the presence of
hydrosilane terminal reductant. The reaction provides a chemoselective catalytic
synthesis of 2H-indazoles, 2H-benzotriazoles, and related fused heterocyclic
systems with good functional group compatibility. On the basis of both
stoichiometric and catalytic mechanistic experiments, the reaction is proposed to
proceed via catalytic PIII/PV?O cycling, where DFT modeling suggests a turnover
limiting (3+1) cheletropic addition between the phosphetane catalyst and
nitroarene substrate. Strain/distortion analysis of the (3+1) transition
structure highlights the controlling role of frontier orbital effects
underpinning the catalytic performance of the phosphetane.
PMID- 28489355
TI - Conjugate of an IgG Binding Domain with Botulinum Neurotoxin A Lacking the
Acceptor Moiety Targets Its SNARE Protease into TrkA-Expressing Cells When
Coupled to Anti-TrkA IgG or Fc-betaNGF.
AB - Numerous naturally occurring toxins can perturb biological systems when they
invade susceptible cells. Coupling of pertinent targeting ligands to the active
domains of such proteins provides a strategy for directing these to particular
cellular populations implicated in disease. A novel approach described herein
involved fusion of one mutated immunoglobulin G (IgG) binding moiety of
staphylococcal protein A to the SNARE protease and translocation domain of
botulinum neurotoxin A (BoNT/A). This chimera could be monovalently coupled to
IgG or via its Fc region to recombinant targeting ligands. The utility of the
resulting conjugates is demonstrated by the delivery of a SNARE protease into a
cell line expressing tropomyosin receptor kinase A (TrkA) through coupling to
anti-TrkA IgG or a fusion of Fc and nerve-growth factor. Thus, this is a
versitile and innovative technology for conjugating toxins to diverse ligands for
retargeted cell delivery of potential therapeutics.
PMID- 28489356
TI - Think Negative: Finding the Best Electrospray Ionization/MS Mode for Your
Analyte.
AB - For the first time, the electrospray ionization efficiency (IE) scales in
positive and negative mode are united into a single system enabling direct
comparison of IE values across ionization modes. This is made possible by the use
of a reference compound that ionizes to a similar extent in both positive and
negative modes. Thus, choosing the optimal (i.e., most sensitive) ionization
conditions for a given set of analytes is enabled. Ionization efficiencies of 33
compounds ionizing in both modes demonstrate that, contrary to general practice,
negative mode allows better sensitivity for 46% of such compounds whereas the
positive mode is preferred for only 18%, and for 36%, the results for both modes
are comparable.
PMID- 28489357
TI - Evaluation of Porous Silicon Oxide on Silicon Microcantilevers for Sensitive
Detection of Gaseous HF.
AB - Sensitive detection of harmful chemicals in industrial applications is pertinent
to safety. In this work, we demonstrate the use of a sensitive silicon
microcantilever (MC) system with a porous silicon oxide layer deposited on the
active side of the MCs that have been mechanically manipulated to increase
sensitivity. Included is the evaluation of porous silicon oxide present on
different geometries of MCs and exposed to varying concentrations of hydrogen
fluoride in humid air. Profilometry and the signal generated by the stress
induced porous silicon oxide (PSO) coating and bending of the MC were used as
methods of evaluation.
PMID- 28489358
TI - Reactions of Platinum Carbonyl Chini Clusters with Ag(NHC)Cl Complexes: Formation
of Acid-Base Lewis Adducts and Heteroleptic Clusters.
AB - The reactions of anionic platinum carbonyl Chini clusters [Pt3n(CO)6n]2- [n = 2
(1), 3 (2), 4 (3)] with Ag(IPr)Cl [IPr = C3N2H2(C6H3iPr2)2] afford the neutral
acid-base Lewis adducts [Pt9(CO)18(AgIPr)2] (4) and [Pt6(CO)12(AgIPr)2] (5).
These are thermally transformed into the homometallic heteroleptic neutral
cluster [Pt3(CO)4(IPr)2] (6). Alternatively, 6 can be obtained from the reactions
of 1-3 with an excess of the free IPr carbene ligand. The formation of 6 is
sometimes accompanied by trace amounts of [Pt4(CO)4(IPr)3] (7). The reaction of 6
with free IPr affords the closely related [Pt3(CO)3(IPr)3] (8) heteroleptic
cluster by substitution of the unique terminal CO ligand with a third IPr ligand.
The reactions of 1-3 with Ag(IMes)Cl [IMes = C3N2H2(C6H2Me3)2] proceed
differently from those involving Ag(IPr)Cl. Indeed, the only product isolated
after workup is the bimetallic tetranuclear cluster [Pt3(CO)3(IMes)3(AgCl)] (9).
9 slowly reacts under a CO atmosphere, resulting in the pentanuclear
[Pt5(CO)7(IMes)3] (10) complex. All of the new clusters 4-10 have been
spectroscopically characterized and their molecular structures determined by X
ray crystallography. 4 and 5 retain the original trigonal-prismatic structures of
the parent anionic Chini clusters, which are capped by two [Ag(IPr)]+ moieties.
Conversely, 6-9 are based on a Pt3 triangular core decorated by CO and N
heterocyclic carbene ligands as well as Pt(CO) (in the case of 7) and AgCl (9)
moieties. 10 displays an edge-bridged tetrahedral geometry.
PMID- 28489359
TI - Liquid Beam Desorption Mass Spectrometry for the Investigation of Continuous Flow
Reactions in Microfluidic Chips.
AB - In this work, we present the combination of microfluidic chips and mass
spectrometry employing laser-induced liquid beam ionization/desorption. The
developed system was evaluated with respect to stable beam generation and laser
parameters as well as solvent compatibility. The device was exemplarily applied
to study a vinylogous Mannich reaction performed in continuous flow on chip. Fast
processes can be observed with this technique which in the future could be
beneficial for studying intermediates or contribute to the elucidation of
reaction mechanisms.
PMID- 28489360
TI - How Does Reference Site Selection Influence Interpretation of Omics Data?:
Evaluating Liver Transcriptome Responses in Male Rainbow Darter (Etheostoma
caeruleum) across an Urban Environment.
AB - Studies quantifying the influence of reference site selection on transcriptomic
profiles in aquatic organisms exposed to complex mixtures are lacking in the
literature, despite the significant implications of such research for the
interpretation of omics data sets. We measured hepatic transcriptomic responses
in fish across an urban environment in the central Grand River watershed
(Ontario, Canada). Adult male rainbow darter (RBD) (Etheostoma caeruleum) were
collected from nine sites at varying distances from two major municipal
wastewater treatment plants (MWWTPs) (Waterloo, Kitchener), including three
upstream reference sites. The transcriptomic response in RBD was independently
compared with that of fish from each of the three reference sites. Data collected
in fish downstream of the Waterloo MWWTP (poorest effluent quality) suggested
that ~15.5% of the transcriptome response was influenced by reference site
selection. In contrast, at sites where the impact of MWWTPs was less-pronounced
and fish showed less of a transcriptome response, reference site selection had a
greater influence (i.e., ~56.9% of transcripts were different depending on the
site used). This study highlights the importance of conducting transcriptomics
studies that leverage more than one reference site, and it broadens our
understanding of the molecular responses in fish in dynamic natural environments.
PMID- 28489361
TI - Soluble Sugar Accumulation Can Influence Seed Size via AN3-YDA Gene Cascade.
AB - In higher plants, seed size is central to many aspects in evolutionary fitness
and is a crucial agricultural trait. In this study, Arabidopsis an3
(angustifolia3) mutants present with increased seed size. Target-gene analysis
revealed that YDA, which encodes a mitogen-activated protein kinase kinase
kinase, is a target gene of AN3. Indeed, the loss of YDA function decreases seed
size. Furthermore, AN3 and YDA mutations both disrupt normal sucrose and glucose
contents and cause altered seed size in an3 or yda mutants. With these results,
we provide a molecular model in which soluble sugar accumulation might affect
seed size regulation via the AN3-YDA gene cascade. Our findings guide the
synthesis of a model that predicts the integration of soluble sugar accumulation
at AN3 to control the establishment of seed size.
PMID- 28489362
TI - Atropisomerism and Conformational Equilibria: Impact on PI3Kdelta Inhibition of 2
((6-Amino-9H-purin-9-yl)methyl)-5-methyl-3-(o-tolyl)quinazolin-4(3H)-one
(IC87114) and Its Conformationally Restricted Analogs.
AB - IC87114 [compound 1, (2-((6-amino-9H-purin-9-yl)methyl)-5-methyl-3-(o
tolyl)quinazolin-4(3H)-one)] is a potent PI3K inhibitor selective for the delta
isoform. As predicted by molecular modeling calculations, rotation around the
bond connecting the quinazolin-4(3H)-one nucleus to the o-tolyl is sterically
hampered, which leads to separable conformers with axial chirality (i.e.,
atropisomers). After verifying that the aS and aR isomers of compound 1 do not
interconvert in solution, we investigated how biological activity is influenced
by axial chirality and conformational equilibrium. The aS and aR atropisomers of
1 were equally active in the PI3Kdelta assay. Conversely, the introduction of a
methyl group at the methylene hinge connecting the 6-amino-9H-purin-9-yl pendant
to the quinazolin-4(3H)-one nucleus of both aS and aR isomers of 1 had a critical
effect on the inhibitory activity, indicating that modulation of the
conformational space accessible for the two bonds departing from the central
methylene considerably affects the binding of compound 1 analogues to PI3Kdelta
enzyme.
PMID- 28489363
TI - Correction to "Air- and Light-Stable P4 and As4 within an Anion-Coordination
Based Tetrahedral Cage".
PMID- 28489364
TI - Fate of d-Fagomine after Oral Administration to Rats.
AB - d-Fagomine is an iminosugar found in buckwheat that is capable of inhibiting the
adhesion of potentially pathogenic bacteria to epithelial mucosa and reducing the
postprandial blood glucose concentration. This paper evaluates the excretion and
metabolism of orally administered d-fagomine in rats and compares outcomes with
the fate of 1-deoxynojirimycin. d-Fagomine and 1-deoxynojirimycin show similar
absorption and excretion kinetics. d-Fagomine is partly absorbed (41-84%, dose of
2 mg/kg of body weight) and excreted in urine within 8 h, while the non-absorbed
fraction is cleared in feces within 24 h. d-Fagomine is partially methylated
(about 10% in urine and 3% in feces). The concentration of d-fagomine in urine
from 1 to 6 h after administration is higher than 10 mg/L, the concentration that
inhibits adhesion of Escherichia coli. Orally administered d-fagomine is
partially absorbed and then rapidly excreted in urine, where it reaches a
concentration that may be protective against urinary tract infections.
PMID- 28489365
TI - Between Descriptors and Properties: Understanding the Ligand Efficiency Trends
for G Protein-Coupled Receptor and Kinase Structure-Activity Data Sets.
AB - The chemical meaning of the ligand efficiency (LE) metrics is explained in this
paper using a large G protein-coupled receptor (GPCR) and kinase structure
activity (IC50, Ki) data set. Although there is a controversy in the literature
regarding both the mathematical validity and the performance of LE, it is in
common use as an early estimator for drug optimization. Apparently, the numerous
con arguments are not convincing enough. We show here for the first time that the
main misunderstanding of the chemical meaning of LE is its interpretation as a
molecular descriptor connected with a single molecule. Instead, LE should be
interpreted as a statistical property. We show that the LE, which is designed as
a regression of a binding property on the heavy atom count (HAC), is correlated
to the reciprocal of the molecular weight because of Avogadro statistics. This
indicates that the hyperbolic model of LE is basically a consequence of a
nonbinding effect, an increase in the number of ligands that are available to a
receptor for smaller molecules, and not a real increase in the binding potency
for a single HAC as interpreted in the literature. Accordingly, we need to
revisit and carefully reevaluate LE-based molecular comparisons.
PMID- 28489366
TI - Correction to Reparameterization of Solute-Solute Interactions for Amino Acid
Sugar Systems Using Isopiestic Osmotic Pressure Molecular Dynamics Simulations.
PMID- 28489367
TI - Franck-Condon Models for Simulating the Band Shape of Electronic Absorption
Spectra.
AB - Band shape is an essential ingredient in the simulation of electronic absorption
spectra. The excitation of multiple series of vibrational levels during an
electronic excitation is a main contributor to band shapes. Here we present two
simple models based on the Franck-Condon displaced-harmonic-oscillator model. The
models are both derived from the time-dependent formulation of electronic
spectroscopy. They assume that the transition dipoles do not depend on geometry
and that the potential energy surfaces are locally quadratic; one model is second
order in time and is called LQ2, and the other is third order in time and is
called LQ3. These models are suitable for simulating the unresolved vibronic band
shapes of electronic spectra that involve many vibrational modes. The models are
straightforward and can be easily applied to simulate absorption spectra that are
composed of many electronic transitions. As compared to carrying out molecular
dynamics simulations, they require relatively few electronic structure
calculations, and the additional cost for constructing the spectra is negligible.
Therefore, the models are suitable for simulating the spectra of complex systems
such as transition-metal complexes.
PMID- 28489369
TI - QM/MM Investigation of Substrate and Product Specificities of Suv4-20h2: How Does
This Enzyme Generate Dimethylated H4K20 from Monomethylated Substrate?
AB - Protein lysine methyltransferases (PKMTs) catalyze the methylation of lysine
residues on histone proteins in the regulation of chromatin structure and gene
expression. In contrast to many other PKMTs for which unmodified lysine is the
methylation target, the enzymes in the Suv4-20 family are able to generate
dimethylated product (H4K20me2) based exclusively on the monomethylated H4K20
substrate (H4K20me1). The origin of such substrate/product specificity is still
not clear. Here, molecular dynamics (MD) and free energy (potential of mean
force) simulations are undertaken using quantum mechanical/molecular mechanical
(QM/MM) potentials to understand the substrate/product specificities of Suv4
20h2, a member of the Suv4-20 family. The free energy barriers for mono-, di-,
and trimethylation in Suv4-20h2 obtained from the simulations are found to be
well correlated with the specificities observed experimentally with the allowed
dimethylation based on the H4K20me1 substrate and prohibited monomethylation and
trimethylation based on H4K20 and H4K20me2, respectively. It is demonstrated that
the reason for the relatively efficient dimethylation is an effective transition
state (TS) stabilization through strengthening the CH...O interactions as well as
the presence of a cation-pi interaction at the transition state. The simulations
also show that the failures of Suv4-20h2 to catalyze monomethylation and
trimethylation are due, respectively, to a less effective TS stabilization and
inability of the reactant complex containing H4K20me2 to adopt a reactive (near
attack) configuration for methyl transfer. The results suggest that care must be
exercised in the prediction of the substrate specificity based only on the
existence of near attack configurations in substrate complexes.
PMID- 28489368
TI - On-the-Fly ab Initio Semiclassical Calculation of Glycine Vibrational Spectrum.
AB - We present an on-the-fly ab initio semiclassical study of vibrational energy
levels of glycine, calculated by Fourier transform of the wavepacket correlation
function. It is based on a multiple coherent states approach integrated with
monodromy matrix regularization for chaotic dynamics. All four lowest-energy
glycine conformers are investigated by means of single-trajectory semiclassical
spectra obtained upon classical evolution of on-the-fly trajectories with
harmonic zero-point energy. For the most stable conformer I, direct dynamics
trajectories are also run for each vibrational mode with energy equal to the
first harmonic excitation. An analysis of trajectories evolved up to 50 000
atomic time units demonstrates that, in this time span, conformers II and III can
be considered as isolated species, while conformers I and IV show a pretty facile
interconversion. Therefore, previous perturbative studies based on the assumption
of isolated conformers are often reliable but might be not completely appropriate
in the case of conformer IV and conformer I for which interconversion occurs
promptly.
PMID- 28489370
TI - Improved Polarizable Dipole-Dipole Interaction Model for Hydrogen Bonding,
Stacking, T-Shaped, and X-H...pi Interactions.
AB - The polarizable dipole-dipole interaction model was formulated in our laboratory
to rapidly simulate hydrogen bonding in biosystems. In this paper, this model is
improved and further parametrized for stacking, T-shaped, and X-H...pi
interactions by adding the orbital overlap term and fitting to 19 CCSD(T)/CBS
interaction energy curves of training dimers. The performance of our model is
assessed through its application to more than 100 complexes, including hydrogen
bonded, stacked, T-shaped, and X-H...pi complexes. For 124 relatively small
testing complexes, our model reproduces benchmark equilibrium intermolecular
distances with a root-mean-square deviation (RMSD) of 0.08 A, and it reproduces
benchmark interaction energies with a 0.64 kcal/mol RMSD. For 14 large
noncovalent complexes, our model reproduces benchmark equilibrium intermolecular
distances with a RMSD of 0.05 A, and it reproduces benchmark interaction energies
with a 0.80 kcal/mol RMSD. Extensive comparisons are made to interaction energies
calculated via the M06-2X and M06-2X-D3 methods, via the well-known
nonpolarizable AMBER99 force field method, via the popular polarizable AMOEBA
force field method, and via semiempirical quantum mechanical (SQM) methods. Our
statistical evaluations show that our model outperforms the AMBER99, AMOEBA, and
SQM methods and is as accurate as the M06-2X and M06-2X-D3 methods. In summary,
the model developed in this work is reasonable, and the newly introduced orbital
overlap term is effective in the accurate modeling of the noncovalent
interactions. Our testing results also indicate that the polarization interaction
term is important in the evaluation of hydrogen bonding, whereas the orbital
overlap is important in examining short hydrogen bonding, T-shaped, and X-H...pi
interactions. Our model may serve as a new tool for modeling biological systems
where hydrogen bonding, stacking, T-shaped, and X-H...pi interactions are of
general importance.
PMID- 28489371
TI - Nickel-Catalyzed Cross-Coupling of Vinyl Dioxanones to Form Enantiomerically
Enriched Cyclopropanes.
AB - Under the conditions of nickel(0) catalysis, enantiomerically enriched vinyl
dioxanones engage boroxines or B2(pin)2 in stereospecific cross-coupling to form
diverse tetrasubstituted cyclopropanes bearing all-carbon quaternary
stereocenters. The collective data corroborate a mechanism involving nickel(0)
mediated benzylic oxidative addition with inversion of stereochemistry followed
by reversible olefin insertion to form a (cyclopropylcarbinyl)nickel complex,
which upon reductive elimination releases the cyclopropane.
PMID- 28489372
TI - Psi4 1.1: An Open-Source Electronic Structure Program Emphasizing Automation,
Advanced Libraries, and Interoperability.
AB - Psi4 is an ab initio electronic structure program providing methods such as
Hartree-Fock, density functional theory, configuration interaction, and coupled
cluster theory. The 1.1 release represents a major update meant to automate
complex tasks, such as geometry optimization using complete-basis-set
extrapolation or focal-point methods. Conversion of the top-level code to a
Python module means that Psi4 can now be used in complex workflows alongside
other Python tools. Several new features have been added with the aid of
libraries providing easy access to techniques such as density fitting, Cholesky
decomposition, and Laplace denominators. The build system has been completely
rewritten to simplify interoperability with independent, reusable software
components for quantum chemistry. Finally, a wide range of new theoretical
methods and analyses have been added to the code base, including functional-group
and open-shell symmetry adapted perturbation theory, density-fitted coupled
cluster with frozen natural orbitals, orbital-optimized perturbation and coupled
cluster methods (e.g., OO-MP2 and OO-LCCD), density-fitted multiconfigurational
self-consistent field, density cumulant functional theory, algebraic-diagrammatic
construction excited states, improvements to the geometry optimizer, and the
"X2C" approach to relativistic corrections, among many other improvements.
PMID- 28489373
TI - Scalemic Caged Xanthones Isolated from the Stem Bark Extract of Garcinia
propinqua.
AB - Seven new caged xanthones, doitunggarcinones E-K (1-7), all as scalemic mixtures
and 10 known compounds (8-17), were isolated from the stem bark extract of
Garcinia propinqua. The structures were elucidated on the basis of spectroscopic
methods. The separation of the enantiomers of 1-6 was achieved by semipreparative
chiral HPLC. The absolute configuration of compound (+)-1 was determined by
single-crystal X-ray crystallographic analysis using Cu Kalpha radiation. The
absolute configurations of the other related compounds were determined from
comparisons of their ECD spectra with that of compound (+)-1. Compounds (-)-6 and
7 showed cytotoxicity against a colon cancer cell line with IC50 values of 14.23
and 23.95 MUM, respectively.
PMID- 28489374
TI - Theoretical Study of the Pair-Correlated F + CHD3(v = 0,nu1 = 1) Reaction: Effect
of CH Stretching Vibrational Excitation.
AB - The F + CHD3(v) reaction is a benchmark system in polyatomic reactions.
Theoretical/experimental comparisons have been reported in recent years that
present some controversies, specifically the role of the reactant CH stretching
vibrational excitation, CHD3(nu1 = 1), on the reactivity of both isotope
channels, DF(v) + CHD2(v') and HF(v) + CD3(v'). However, in many cases, these
comparisons are not made on an equal footing. Previous theoretical studies were
concerned with overall reactivity of each isotope channel, while fine velocity
map imaging experiments provided results in a product pair-correlated manner. In
order to shed some light on these controversies, we perform here a pair
correlated theory/experiment comparison for the title reaction, using quasi
classical trajectory calculations on a full dimensional potential energy surface.
When these calculations are analyzed in a quantum spirit, i.e., by discarding
those trajectories whose results do not meet quantum-mechanical requirements and
aiming to reproduce stringent experimental constraints, some of the discrepancies
on overall reactivity and the effect of the CH vibrational excitation are now
resolved. Agreement with the available experimental studies, though still
qualitative in some aspects, has noticeably improved.
PMID- 28489375
TI - Involvement of the Glucocorticoid Receptor in Pro-inflammatory Transcription
Factor Inhibition by Daucane Esters from Laserpitium zernyi.
AB - Species of the genus Laserpitium have been used traditionally to treat
inflammation and infection. From the herb of Laserpitium zernyi, six new
compounds were isolated and their structures elucidated (using IR, NMR, HRMS
data) as derivatives of 8-daucene-2,4,10-triol (1, 2, and 4), 7-daucene-2,4,10
triol (3), a lapiferin derivative featuring a C-2 ester moiety (5), and a daucane
featuring an exomethylene group at C-8 (6). Also isolated were the rare daucanes
vaginatin (7) and laserpitin (8). In a search for selective glucocorticoid
receptor (GR) modulators, the compounds were tested for their capacity to inhibit
NF-kappaB and AP-1 pro-inflammatory factors and for a potential competitive
effect on a dexamethasone (Dex)-induced GR-driven glucocorticoid response element
(GRE) reporter gene. The new 2beta-angeloyloxy-10alpha-acetoxy-8-daucene-2,4,10
triol (2) significantly inhibited transactivation of both NF-kappaB and AP-1,
while vaginatin (7) was the most active of the compounds tested in blocking AP-1.
Both compounds competitively repressed Dex-induced GRE-driven promoter
activities, indicative of a potential role for GR. In addition, a decreased
potential to inhibit NF-kappaB was apparent in GR knockout A549 cells. In line
with the transcriptional assays, compounds 2 and 7 also significantly lowered CCL
2 chemokine production, albeit to a lesser extent than Dex. The results suggest
that daucanes may be interesting candidates in the search for compounds with GR
modulating activities.
PMID- 28489376
TI - Interplay Between pi-Stacking and Hydrogen Bonding in the Self-Association of
Different Isomers of Naphthalenedicarboxylic Acid.
AB - Using proton and carbon chemical shifts, we investigated the self-association of
three isomers of naphthalenedicarboxylic acid, a model for the aggregation of
asphaltenes. Experimental proton chemical shifts of each isomer were measured as
a function of concentration in an aprotic solvent. Several potential structures
of the monomer and dimer of each naphthalenedicarboxylic acid were considered,
and calculated proton chemical shifts for the potential monomer and dimer
structures were compared to the experimental chemical shifts to find the weighted
average structure that best fit the experimental shifts. Calculated carbon
chemical shifts were also compared to experimental values. The chemical shift
comparison and calculated energies indicate that pi-stacked dimers are not likely
to contribute significantly to the dimer structure of any of the three
naphthalenedicarboxylic acid isomers studied.
PMID- 28489377
TI - Svetamycins A-G, Unusual Piperazic Acid-Containing Peptides from Streptomyces sp.
AB - Seven new halogenated peptides termed svetamycins A-G (1-7) have been isolated
from laboratory cultures of a Streptomyces sp. Svetamycins A-D, F, and G are
cyclic depsipeptides, whereas svetamycin E is a linear analogue of svetamycin C.
Their structures were determined using extensive spectroscopic analysis, and
their stereochemical configuration was established by a combination of NMR data,
quantum mechanical calculations, and chemical derivatizations. Svetamycins are
characterized by the presence of a hydroxyl acetic acid and five amino acids
including a rare 4,5-dihydroxy-2,3,4,5-tetrahydropyridazine-3-carboxylic acid, a
gamma-halogenated piperazic acid, and a novel delta-methylated piperazic acid in
svetamycins B-C, E, and G. Moreover, isotope-labeled substrate feeding
experiments demonstrated ornithine as the precursor of piperazic acid and that
methylation at the delta position of the piperazyl scaffold is S-adenosyl-l
methionine (SAM)-dependent. Svetamycin G, the most potent antimicrobial of this
suite of compounds, inhibited the growth of Mycobacterium smegmatis with an MIC80
value of 2 MUg/mL.
PMID- 28489378
TI - Radical Chain Reduction of CCl4 Initiated by Illumination of SPEEK Solutions.
AB - Efficient reduction of CCl4 took place upon exposure to 350-nm photons of aqueous
solutions containing sulfonated poly(ether etherketone) (SPEEK) as a sensitizer
and either poly(vinyl alcohol) (PVA) or HCO2H/HCO2- buffer. The photoreaction
formed chloride ions whose concentration increased linearly with time in
solutions free of O2, whereas slower reductions occurred in the presence of air.
Utilization of formate buffer as the H-atom donor yielded photoreactions at least
10 times faster than those in the presence of PVA and generated CHCl3 as another
reaction product. The quantum yield of chloride ion formation, o(Cl-), was found
to be a function of both the SPEEK concentration and concentration of formate
buffer. Whereas the quantum efficiency increased steadily with decreasing
solution acidity, a drastic surge in the reaction rate occurred in neutral
solutions. o(Cl-) first increased rapidly to a maximum value exceeding 1 at pH
7.3 and then decreased thereafter. The dependence of r(Cl-) on (I0)1/2, where I0
is the light intensity, and the occurrence of postirradiation formation of Cl-
through the reduction of CCl4 in the dark are further evidence that the
photoreaction proceeded by a chain process. Several of the kinetic features were
rationalized by means of a mechanism involving the alpha-hydroxy radicals of
SPEEK and *CCl3 as chain carriers.
PMID- 28489379
TI - Hydroxy-Substituted Heteroarylpiperazines: Novel Scaffolds for beta-Arrestin
Biased D2R Agonists.
AB - By means of a formal structural hybridization of the antipsychotic drug
aripiprazole and the heterocyclic catecholamine surrogates present in the beta2
adrenoceptor agonists procaterol and BI-167107 (4), we designed and synthesized a
collection of novel hydroxy-substituted heteroarylpiperazines and
heteroarylhomopiperazines with high dopamine D2 receptor (D2R) affinity. In
contrast to the weak agonistic behavior of aripiprazole, these ligands are
capable of effectively mimicking those interactions of dopamine and the D2R that
are crucial for an active state, leading to the recruitment of beta-arrestin-2.
Interestingly, some ligands show considerably lower intrinsic activity in guanine
nucleotide exchange experiments at D2R and consequently represent biased agonists
favoring beta-arrestin-2 recruitment over canonical G protein activation. The
ligands' agonistic properties are substantially driven by the presence of an
endocyclic H-bond donor.
PMID- 28489380
TI - Facile Approach to Perylenemonoimide with Short Side Chains for Nonfullerene
Solar Cells.
AB - Electron acceptors based on perylene monoimide (PMI) are rare due to the
synthetic challenge. Herein, starting from commercially available perylene
dianhydride, brominated perylene monoimide (PMI-Br) with short side chains and
good solubility was efficiently synthesized in a high overall yield of 71%. With
PMI-Br as the intermediate, acceptor-donor-acceptor type electron acceptors with
low-lying LUMO energy levels and strong visible absorption were successfully
obtained. The nonfullerene bulk heterojunction solar cells based on these
acceptors were fabricated with the highest PCE of 1.3%.
PMID- 28489381
TI - Molecular Mechanism of the Reaction Specificity in Threonine Synthase: Importance
of the Substrate Conformations.
AB - Threonine synthase (ThrS) catalyzes the final chemical reaction of l-threonine
biosynthesis from its precursor, O-phospho-l-homoserine. As the phosphate ion
generated in its former half reaction assists its latter reaction, ThrS is
recognized as one of the best examples of product-assisted catalysis. In our
previous QM/MM study, the chemical reactions for the latter half reactions, which
are critical for the product-assisted catalysis, were revealed. However, accurate
free energy changes caused by the conformational ensembles and entrance of water
molecules into the active site are unknown. In the present study, by performing
long-time scale MD simulations, the free energy changes by the divalent anions
(phosphate or sulfate ions) and conformational states of the intermediate states
were theoretically investigated. We found that the calculated free energy double
differences are in good agreement with the experimental results. We also revealed
that the phosphate ion contributes to forming hydrogen bonds that are suitable
for the main reaction progress. This means that the conformation of the active
site amino acid residues and the substrate, and hence, the tunable catalysis, are
controlled by the product phosphate ion, and this clearly demonstrates a
molecular mechanism of the product-assisted catalysis in ThrS.
PMID- 28489382
TI - Antimicrobial Spirotetronate Metabolites from Marine-Derived Micromonospora
harpali SCSIO GJ089.
AB - Two new spirotetronate aglycones, 22-dehydroxymethyl-kijanolide (1) and 8-hydroxy
22-dehydroxymethyl-kijanolide (2), along with seven new spirotetronate
glycosides, microsporanates A-F (3-8) and tetrocarcin P (9), together with three
known tetrocarcins [tetrocarcins A (10), B (11), and AC6H (12)], were isolated
from fermentation broths of the marine-derived Micromonospora harpali SCSIO
GJ089. The structures of 1-9 were elucidated on the basis of 1D and 2D NMR and MS
spectroscopic data. Compounds 3-8 feature an alpha,beta-unsaturated carbonyl
moiety within their spirotetronate skeletons. Moreover, compounds 3-12 displayed
strong to moderate antibacterial activities against Gram positive bacteria
Bacillus thuringiensis BT01 and B. subtilis BS01 with MIC values ranging from
0.016 to 8.0 MUg/mL.
PMID- 28489383
TI - Confined Electroconvective and Flexoelectric Instabilities Deep in the
Freedericksz State of Nematic CB7CB.
AB - We report wormlike flexoelectric structures evolving deep in the Freedericksz
state of a nematic layer of the liquid crystal cyanobiphenyl-(CH2)7
cyanobiphenyl. They form in the predominantly splay-bend thin boundary layers and
are built up of solitary flexoelectric domains of the Bobylev-Pikin type. Their
formation is possibly triggered by the gradient flexoelectric surface instability
that remains optically discernible up to unusually high frequencies. The
threshold voltage at which the worms form scales as square root of the frequency;
in their extended state, worms often appear as labyrinthine structures on a
section of loops that separate regions of opposite director deviation. Such
asymmetric loops are also derived through pincement-like dissociation of ring
shaped walls. Formation of isolated domains of bulk electroconvection precedes
the onset of surface instabilities. In essence, far above the Freedericksz
threshold, the twisted nematic layer behaves as a combination of two orthogonally
oriented planar half-layers destabilized by localized flexoelectric distortion.
PMID- 28489384
TI - Rethinking Dithiothreitol-Based Particulate Matter Oxidative Potential: Measuring
Dithiothreitol Consumption versus Reactive Oxygen Species Generation.
AB - We measured the rate of generation of reactive oxygen species (ROS) [hydroxyl
radicals (*OH) and hydrogen peroxide (H2O2)] catalyzed by ambient particulate
matter (PM) in the dithiothreitol (DTT) assay. To understand the mechanism of ROS
generation, we tested several redox-active substances, such as 9,10
phenanthrenequinone (PQ), 5-hydroxy-1,4-naphthoquinone (5H-1,4NQ), 1,2
naphthoquinone (1,2-NQ), 1,4-naphthoquinone (1,4-NQ), copper(II), manganese(II),
and iron (II and III). Both pure compounds and their mixtures show different
patterns in DTT oxidation versus ROS generation. The quinones, known to oxidize
DTT in the efficiency order of PQ > 5H-1,4NQ > 1,2-NQ > 1,4-NQ, show a different
efficiency order (5H-1,4NQ > 1,2-NQ ~ PQ > 1,4-NQ) in the ROS generation. Cu(II),
a dominant metal in DTT oxidation, contributes almost negligibly to the ROS
generation. Fe is mostly inactive in DTT oxidation, but shows synergistic effect
in *OH formation in the presence of other quinones (mixture/sum > 1.5). Ten
ambient PM samples collected from an urban site were analyzed, and although DTT
oxidation was significantly correlated with H2O2 generation (Pearson's r = 0.91),
no correlation was observed between DTT oxidation and *OH formation. Our results
show that measuring both DTT consumption and ROS generation in the DTT assay is
important to incorporate the synergistic contribution from different aerosol
components and to provide a more inclusive picture of the ROS activity of ambient
PM.
PMID- 28489385
TI - Nanoscaled Amorphous TiO2 Hollow Spheres: TiCl4 Liquid Droplet-Based Hydrolysis
Fabrication and Strong Hollow Structure-Enhanced Surface-Enhanced Raman
Scattering Effects.
AB - A very simple route is developed for fast fabrication of nanosized amorphous
titanium dioxide (TiO2) hollow spheres (THPs) just via dropping the pure four
titanium chloride (TiCl4) liquid droplets into deionized water at around room
temperature. The THPs, at around 80 nm in mean diameter, can be formed within a
few seconds after dropping TiCl4 droplets into water. The shell layers of the
obtained THPs are amorphous and porous in structure with a porosity of 58-80% and
show a linear increase in thickness with the size of THPs. Further experiments
have revealed that the reaction temperature, initial pH value, and size of the
TiCl4 droplet are crucial to the formation, size, productivity, and
microstructure of the THPs. A model is proposed on the basis of the fragmentation
of liquid droplets, hydrolysis-induced formation, and inward growth of TiO2 shell
layers, which can well describe the formation of the THPs. Importantly, such
amorphous nanoscaled THPs have exhibited some strong hollow structure-enhanced
performances. Typically, the THP-built film shows the highest reflectivity in the
visible region compared to the other structured TiO2 films. Especially, if it
supports the film of the Au nanoparticle, the surface-enhanced Raman scattering
effect is significantly enhanced by more than 1 order of magnitude. This work
provides not only a simple and quick fabrication method for the THPs but also a
new member for their family.
PMID- 28489386
TI - One-Step Synthesis of Hydrophobic Multicompartment Organosilica Microspheres with
Highly Interconnected Macro-mesopores for the Stabilization of Liquid Marbles
with Excellent Catalysis.
AB - The combination of an emulsion template with polymerization is a very convenient
approach to the one-step realization of both simple control porous structures via
a change in emulsion formulation and easy functionalization via the concomitant
choice of an on-demand monomer. A major challenge of this approach is the
inherent instability of the oil/water interface in emulsions, especially the
occurrence of chemical reactions in oil or aqueous phases. This study reports the
pioneering preparation of highly interconnected macro-mesopores and
multicompartment (HIMC) vinyl organosilica microspheres with hydrophobicity by
the one-step formation of W/O/W emulsions acting as a template. The emulsion
system consists of acidified deionized water, a stabilizer, and
vinyltriethoxysilane (VTEO) in which VTEO can be used to produce an organosilica
skeleton of the resultant microsphere by a sol-gel process. The study
demonstrated that the marvelous stability of W/O/W emulsions aids the formation
of multicompartment organosilica microspheres with highly interconnected macro
mesopores by emulsion droplets rather than single-compartment (SC) microspheres.
Meanwhile, the internal porous structure and surface morphology of as-prepared
organosilica microspheres could be largely tuned by a simple variation of the pH
value, the volume fraction of the water phase, and the stabilizer concentration
in the initiating multiemulsions. Benefiting from such a well-orchestrated
structure and the existence of numerous vinyl groups on the surface, HIMC
organosilica microspheres exhibit very high hydrophobicity (with a water contact
angle larger than 160 degrees ), which allows them to stabilize liquid marbles
with excellent stability and high mechanical robustness. Because of its strong
catalyst, Ag nanoparticles within HIMC organosilica microspheres enable Ag/HIMC
vinyl organosilica microsphere-based liquid marbles to be an efficient catalytic
microreactor, realizing the complete degradation of MB to leuco methylene blue by
NaBH4 in 10 min. The result of this work could provide some guidance for the
easy, low-cost, benign preparation of HIMC microspheres having the potential to
be excellent supporter of metal nanoparticles or other functionalized compounds
for applications in sensing, optoelectronics, and catalysis.
PMID- 28489387
TI - Reactive Hypersaline Route: One-Pot Synthesis of Porous Photoactive
Nanocomposites.
AB - Herein, porous photoactive nanocomposites are prepared by a simple one-pot
synthesis approach using a salt and aqueous media. Within this reactive
hypersaline route, the salt not only serves in the structuring of the composite
but also becomes an integral active part of it. Here, the addition of sodium
thiocyanate to a titania precursor guides, on the one hand, the formation of
needle-shaped nanoparticles and, on the other hand, forms yellow compound
isoperthiocyanic acid, which is homogeneously incorporated into the porous
nanocomposite. Compared to a pure titania reference, this material reveals a 7
fold-increased photodegradation rate of Rhodamine B as a model compound. This
reveals the reactive hypersaline route to be a promising and facile synthesis
route toward photoactive porous materials.
PMID- 28489388
TI - Ultrathin and Highly Passivating Silica Shells for Luminescent and Water-Soluble
CdSe/CdS Nanorods.
AB - Microemulsion (water-in-oil) methods enable the encapsulation of individual
nanoparticles into SiO2 spheres. The major drawbacks of this method, when applied
for silica encapsulation of anisotropic nanorods (NRs), are spatially unequal
silica growth and long reaction times (24 h at least). In this work, various
tetraalkoxysilanes [tetramethyl orthosilicate (TMOS), tetraethyl orthosilicate
(TEOS), and tetrapropyl orthosilicate (TPOS)] with different alkyl-chain lengths
were used as silica precursors in attempt to tune the silanization behavior of
CdSe/CdS NRs in a microemulsion system. We find enhanced spatial homogeneity of
silica growth with decreasing alkyl-chain length of the tetraalkoxysilanes. In
particular, by use of TMOS as the precursor, NRs can be fully encapsulated in a
continuous thin (<=5 nm) silica shell within only 1 h reaction time.
Surprisingly, the thin silica shell showed a superior shielding ability to acidic
environment, even compared to the 30 nm thick shell prepared by use of TEOS. Our
investigations suggest that the lower steric hindrance of TMOS compared to TEOS
or TPOS strongly promotes homogeneous growth of the silica shells, while its
increased hydrolysis rate decreases the porosity of these shells.
PMID- 28489389
TI - Stabilization of Foam Lamella Using Novel Surface-Grafted Nanocellulose-Based
Nanofluids.
AB - To solve the potential risk of present oilfield chemistries to subterranean
environment, our group contributes to the development of "green" petroleum
production processes. This proof-of-concept research studied the well-defined
nanocellulose-based nanofluids, i.e., original (NC), AMPS grafted (NC-KY), and
AMPS and hydrophobic chains grafted (NC-KYSS), in stabilizing foam lamella for
potential use in enhanced oil recovery (EOR). The data showed that the
collaboration of the surface-functional nanocellulose considerately improved the
foam stability particularly in the presence of hydrocarbons due to the thickened
foam film coupled with the molecular interactions at interior lamella. Since the
grafted AMPS and alkyl chains, NC-KYSS noticeably enhanced foam quality compared
against NC and NC-KY. With the increase in gas pressure, the lamella stabilizing
effect of NC-KYSS became increasingly significant. The coflowing behaviors of
foam with oleic phase in porous media were examined in a five-spot visualization
micromodel (15 cm * 15 cm * 1 cm) and identified using a digital analysis method.
The defoaming/destabilizing effect of hydrocarbons was fairly notable in porous
media, causing the foam to finger through the formed "oil bank". However, a tough
displacement front was constructed when the surfactant synergized with NC-KYSS
due to the stabilized foam lamella and 12% of incremental oil recovery was
produced.
PMID- 28489390
TI - Synthesis of Ni9S8/MoS2 heterocatalyst for Enhanced Hydrogen Evolution Reaction.
AB - We demonstrate a heterostructure Ni9S8/MoS2 hybrid with tight interface
synthesized via an improved hydrothermal method. As compared to pure MoS2, the
increased surface area and the shorten charge transport pathway in the layered
hybrid significantly promote the photocatalytic efficiency for hydrogen evolution
reaction (HER). In particularly, the optimized Ni9S8/MoS2 hybrid with 20 wt %
Ni9S8 exhibits the highest photocatalytic activity with HER value of 406 MUmolg
1h-1, which is enhanced by 70% compared to that of pure MoS2 nanosheets (285.0
MUmolg-1h-1). Moreover, the value is 4 times more than the commercial MoS2 (92.0
MUmolg-1h-1), indicating the high potential of the hybrid in the catalytic
fields.
PMID- 28489391
TI - Helium Nanobubbles Enhance Superelasticity and Retard Shear Localization in Small
Volume Shape Memory Alloy.
AB - The intriguing phenomenon of metal superelasticity relies on stress-induced
martensitic transformation (SIMT), which is well-known to be governed by
developing cooperative strain accommodation at multiple length scales. It is
therefore scientifically interesting to see what happens when this natural length
scale hierarchy is disrupted. One method is producing pillars that confine the
sample volume to micrometer length scale. Here we apply yet another intervention,
helium nanobubbles injection, which produces porosity on the order of several
nanometers. While the pillar confinement suppresses superelasticity, we found the
dispersion of 5-10 nm helium nanobubbles do the opposite of promoting
superelasticity in a Ni53.5Fe19.5Ga27 shape memory alloy. The role of helium
nanobubbles in modulating the competition between ordinary dislocation slip
plasticity and SIMT is discussed.
PMID- 28489392
TI - Theoretical Study on the Negative Thermal Expansion Perovskite LaCu3Fe4O12:
Pressure-Triggered Transition of Magnetism, Charge, and Spin State.
AB - The A-site ordered negative thermal expansion material LaCu3Fe4O12 (LaCFO) was
comprehensively investigated by using first-principles calculations. A pressure
triggered crystal structural phase transition from space group Im3 (No. 204) to
Pn3 (No. 201) and magnetic transformation from a G-type antiferromagnetic (G_AFM)
ground state to ferrimagnetic (FerriM) coupling were observed in LaCFO via
gradual compression of the equilibrium volume. Correspondingly, the Fe-Cu
intersite charge transfer from Fe to Cu 3dxy orbital, expressed as 4Fe3+ + 3Cu3+
> 4Fe3.75+ + 3Cu2+, was simulated along with the magnetic phase transformation
from the G_AFM configuration to the FerriM state. Intriguingly, the Fe charge
disproportionation, formulated as 8Fe3.75+ -> 5Fe3+ + 3Fe5+, appeared and was
attributed to the strong hybridization between Fe 3d and O 2p orbitals in the
FerriM state when the volumes were substantially compressed up to less than or
equal to 80%V. Meanwhile, the external hydrostatic pressure also leads to a spin
flip from a high-spin Fe3+ antiferromagnetically arranged LaCu3+3Fe3+4O12 Mott
insulator at low pressure and goes through a FerriM LaCu2+3Fe3.75+4O12 half-metal
to a low-spin FerriM coupled LaCu2+3Fe3+5/2Fe5+3/2O12 metal at high pressure.
Therefore, the crossover from high spin to low spin is responsible for the charge
disproportionation in LaCFO. Essentially, the charge transfer and spin flip
originate from the discontinuous changes of metal-oxygen bond lengths and angles
in the compressed atomic structure. Finally, the negative thermal expansion
behavior and mechanism of LaCFO were theoretically examined and clearly revealed.
PMID- 28489393
TI - Ag2O/TiO2 Nanocomposite Heterostructure as a Dual Functional Semiconducting
Substrate for SERS/SEIRAS Application.
AB - Surface-enhanced Raman spectroscopy (SERS) and surface-enhanced infrared
absorption spectroscopy (SEIRAS) are complementary and powerful techniques for
molecular characterization and detection. However, studies on substrates that can
enhance both Raman and IR singles are extremely scanty. Here, we reported a
hybrid semiconductor material (Ag2O/TiO2) coupled with a portable solid support
served as a dual functional platform for both SERS and SEIRAS applications. A
facile two-step deposition method was used to synthesize Ag2O/TiO2 nanocomposite
on a flexible polymeric membrane without bringing any external chemical capping
agent and background signal. The presence of Ag2O was proposed to enrich the
photogenerated electrons onto TiO2 surface and facilitate the photon-induced
charge transfer (PICT) between TiO2 and adsorbate. The heterostructure of
Ag2O/TiO2 could bring additional enhancement. The enhancement factor from such
hybrid semiconducting substrate was at least one or two orders of magnitude over
traditional semiconducting materials and comparable to noble metals.
Additionally, this substrate enabled the ultratrace detection regardless of the
more Raman- or IR-active molecules and displayed distinct quantitative capacities
for SERS and SEIRAS. High reproducibility of the SERS/SEIRAS spectra further
confirmed the reliability and reproducibility of our substrates.
PMID- 28489394
TI - Surface-Engineering of Ultrathin Gold Nanowires: Tailored Self-Assembly and
Enhanced Stability.
AB - Gold nanowires with a mean diameter of 1.7 nm were synthesized by reduction of
HAuCl4 in a solution of oleylamine (OY) in hexane. A bilayer of oleylammonium
chloride/oleylamine at the surface of the raw nanowires was evidenced by NMR and
diffusion ordered spectroscopy (DOSY) experiments. After washing a monolayer of
oleylammonium chloride remained at the surface of the nanowires. The
oleylammonium chloride layer could be progressively replaced by a phosphine shell
as evidenced with NMR and DOSY experiments, which are in good agreement with the
adsorption energies given by density functional theory calculations. The
nanowires crystallize into hexagonal superlattices with a lattice parameter that
can be tailored depending on the ligand shell. Small-angle X-ray scattering
showed the following lattice parameters: Au@OY+Cl-(OY) (a = 7.2 nm) > Au@TOPO/OY
(a = 6.6 nm) > Au@ OY+Cl- (a = 4.1 nm) > Au@TOP (a = 3.75 nm). This is one of a
few examples of surface modification of ultrathin nanowires that does not alter
their morphology. Moreover, the nanowires coated with phosphines exhibited long
time stability (at the opposite of other ligands like thiols) opening the way to
more complex functionalization.
PMID- 28489395
TI - Identification of Potent and Selective CYP1A1 Inhibitors via Combined Ligand and
Structure-Based Virtual Screening and Their in Vitro Validation in Sacchrosomes
and Live Human Cells.
AB - Target structure-guided virtual screening (VS) is a versatile, powerful, and
inexpensive alternative to experimental high-throughput screening (HTS). To
discover potent CYP1A1 enzyme inhibitors for cancer chemoprevention, a commercial
library of 50 000 small molecules was utilized for VS guided by both ligand and
structure-based strategies. For experimental validation, 300 ligands were
proposed based on combined analysis of fitness scores from ligand based e
pharmacophore screening and docking score, prime MMGB/SA binding affinity and
interaction pattern analysis from structure-based VS. These 300 compounds were
screened, at 10 MUM concentration, for in vitro inhibition of CYP1A1-Sacchrosomes
(yeast-derived microsomal enzyme) in the ethoxyresorufin-O-de-ethylase assay.
Thirty-two compounds displayed >50% inhibition of CYP1A1 enzyme activity at 10
MUM. 2-Phenylimidazo-[1,2-a]quinoline (5121780, 119) was found to be the most
potent with 97% inhibition. It also inhibited ~95% activity of CYP1B1 and CYP1A2,
the other two CYP1 enzymes. The compound 5121780 (119) showed high selectivity
toward inhibition of CYP1 enzymes with respect to CYP2 and CYP3 enzymes (i.e.,
there was no detectable inhibition of CYP2D6/CYP2C9/CYP2C19 and CYP3A4 at 10
MUM). It was further investigated in live CYP-expressing human cell system, which
confirmed that compound 5121780 (119) potently inhibited CYP1A1, CYP1A2, CYP1B1
enzymes with IC50 values of 269, 30, and 56 nM, respectively. Like in
Sacchrosomes, inhibition of CYP2D6/CYP2C9/CYP2C19 and CYP3A4 enzymes, expressed
within live human cells, could hardly be detected at 10 MUM. The compound 119
rescued CYP1A1 overexpressing HEK293 cells from CYP1A1 mediated benzo[a]pyrene
(B[a]P) toxicity and also overcame cisplatin resistance in CYP1B1 overexpressing
HEK293 cells. Molecular dynamics simulations of 5121780 (119) with CYP1 enzymes
was performed to understand the interaction pattern to CYP isoforms. Results
indicate that VS can successfully be used to identify promising CYP1A1
inhibitors, which may have potential in the development of novel cancer chemo
preventive agents.
PMID- 28489396
TI - Fe/Cu-Mediated One-Pot Ketone Synthesis.
AB - An Fe/Cu-mediated one-pot ketone synthesis was reported. Unlike Ni- and Pd
mediated one-pot ketone syntheses, the reported Fe/Cu-mediated method allowed
selective activation and coupling of alkyl iodides over vinyl iodides. The newly
developed one-pot ketone synthesis was applied to a synthesis of vinyl
iodide/ketone 13, the left half of halichondrin B, as well as vinyl iodide/ketone
8a, the C20-C26 building block of halichondrins.
PMID- 28489397
TI - Amine-Controlled Divergent Reaction: Iminolactonization and Olefination in the
Presence of a Cu(I) Catalyst.
AB - alpha-Bromoamides and styrenes underwent iminolactonization reactions
(carbooxygenation), in which simultaneous C-C and C-O formation occurred in the
presence of a copper catalyst with triethylamine as the base. Conversely,
olefination reactions occurred in the presence of a Cu catalyst with piperidine
as the base. The selectivities in those reactions were very high.
PMID- 28489398
TI - Simultaneously Enhancing Light Emission and Suppressing Efficiency Droop in GaN
Microwire-Based Ultraviolet Light-Emitting Diode by the Piezo-Phototronic Effect.
AB - Achievement of p-n homojuncted GaN enables the birth of III-nitride light
emitters. Owing to the wurtzite-structure of GaN, piezoelectric polarization
charges present at the interface can effectively control/tune the optoelectric
behaviors of local charge-carriers (i.e., the piezo-phototronic effect). Here, we
demonstrate the significantly enhanced light-output efficiency and suppressed
efficiency droop in GaN microwire (MW)-based p-n junction ultraviolet light
emitting diode (UV LED) by the piezo-phototronic effect. By applying a -0.12%
static compressive strain perpendicular to the p-n junction interface, the
relative external quantum efficiency of the LED is enhanced by over 600%.
Furthermore, efficiency droop is markedly reduced from 46.6% to 7.5% and
corresponding droop onset current density shifts from 10 to 26.7 A cm-2. Enhanced
electrons confinement and improved holes injection efficiency by the piezo
phototronic effect are revealed and theoretically confirmed as the physical
mechanisms. This study offers an unconventional path to develop high efficiency,
strong brightness and high power III-nitride light sources.
PMID- 28489399
TI - Synthesis of Tetraaza[8]circulenes from Tetrathia[8]circulenes through an SNAr
Based Process.
AB - The synthesis of highly planar tetraaza[8]circulenes from tetrathia[8]circulenes
through oxidation followed by a nucleophilic aromatic substitution reaction with
arylamines is presented. Photophysical and electrochemical properties of
tetraaza[8]circulenes were investigated and compared to those of
tetrathia[8]circulenes. The tetraaza[8]circulene exhibited bright fluorescence
both in solution and solid states.
PMID- 28489400
TI - Antirotaviral Activity of Bovine and Ovine Dairy Byproducts.
AB - Rotaviral gastroenteritis is associated with significant morbidity in developed
countries and a high rate of infant mortality in developing countries. Diverse
studies have demonstrated that a wide range of milk-derived fractions exhibit
antirotaviral activity. The present study shows the antirotaviral activity of
some bovine and ovine dairy byproducts, buttermilk, butter serum, and milk fat
globule membrane (MFGM), and evaluates the effect of cream washing and heat
treatment on that activity. Furthermore, the rotavirus-neutralizing activity was
evaluated for some MFGM proteins, such as xanthine oxidase and lactophorin. Ovine
and bovine buttermilk reached rotavirus-neutralizing values of 51.3 and 32.2%, at
1 mg/mL, respectively. The cream washing process led to a significant decrease in
the antirotaviral activity of fractions. This activity was also influenced by
heat treatment. Treatment at 75 degrees C for 20 s caused 24.6 and 36.1%
decreases of activity in bovine and ovine buttermilk, respectively, and 85
degrees C for 10 min caused decreases of 80.9 and 79.0% in both fractions,
respectively.
PMID- 28489401
TI - Molecular Dynamics-Markov State Model of Protein Ligand Binding and Allostery in
CRIB-PDZ: Conformational Selection and Induced Fit.
AB - Conformational selection and induced fit are well-known contributors to ligand
binding and allosteric effects in proteins. Molecular dynamics (MD) simulations
now enable the theoretical study of protein-ligand binding in terms of ensembles
of interconverting microstates and the population shifts characteristic of
"dynamical allostery." Here we investigate protein-ligand binding and allostery
based on a Markov state model (MSM) with states and rates obtained from all-atom
MD simulations. As an exemplary case, we consider the single domain protein par-6
PDZ with and without ligand and allosteric effector. This is one of the smallest
proteins in which allostery has been experimentally observed. In spite of the
increased complexity intrinsic to a statistical ensemble perspective, we find
that conformational selection and induced fit mechanisms can be readily
identified in the analysis. In the nonallosteric pathway, MD-MSM shows that PDZ
binds ligand via conformational selection. However, the allosteric pathway
requires an activation step that involves a conformational change induced by the
allosteric effector Cdc42. Once in the allosterically activated state, we find
that ligand binding can proceed by conformational selection. Our MD-MSM model
predicts that allostery in this and possibly other systems involves both induced
fit and conformational selection, not just one or the other.
PMID- 28489402
TI - Iodine-Catalyzed Facile Approach to Sulfones Employing TosMIC as a Sulfonylating
Agent.
AB - A novel iodine-catalyzed functionalization of a variety of olefins and alkynes
and direct decarboxylative functionalization of cinnamic and propiolic acids with
TosMIC to provide access to various vinyl, allyl, and beta-iodo vinylsulfones is
described. This simple, efficient, and environmentally benign approach employing
inexpensive molecular iodine as a catalyst demonstrates a versatile protocol for
the synthesis of highly valuable sulfones, rendering it attractive to both
synthetic and medicinal chemistry.
PMID- 28489403
TI - Development of a Chlorantraniliprole Microcapsule Formulation with a High Loading
Content and Controlled-Release Property.
AB - Microcapsule formulations have been widely developed and used in agriculture to
improve pesticide utilization and reduce environmental pollution. However,
commercial formulations of chlorantraniliprole (CAP) are only traditional
formulations due to poor solubility of CAP in organic solvents. Here, adopting a
solid in oil in water (S/O/W) double-emulsion method combined with premix
membrane emulsion, we successfully constructed CAP microcapsule formulations with
a high loading content. The microcapsule formulations with good light and thermal
stability showed a significantly sustained release for a long period, which could
be optimally regulated by tuning the surface porosity and size of the porous
microcapsules. Bioassay studies showed that control efficacy of the porous
microcapsule formulations against Plutella xylostella was superior to that of the
commercial formulation. These results demonstrated that such a porous
microcapsule delivery system should have great potential for further exploration
as a commercial CAP formulation.
PMID- 28489404
TI - Synthetic Routes toward Acidic Pentasaccharide Related to the O-Antigen of E.
coli 120 Using One-Pot Sequential Glycosylation Reactions.
AB - Concise syntheses of the acidic pentasaccharide, related to the O-antigenic
polysaccharide of Escherichia coli 120, as its p-methoxyphenyl glycoside, have
been achieved using a one-pot sequential glycosylation technique. The
glycosylations have been accomplished either by the activation of the
thioglycosides using NIS in the presence of FeCl3 or by a preactivation by Ph2SO,
TTBP, Tf2O, and the activation of the trichloroacetimidates using FeCl3 alone or
TMSOTf. Most of the intermediate steps are high yielding, and the stereo outcomes
of the glycosylation steps were excellent. The syntheses of the targeted
pentasaccharide have been performed with both three- and four-component, one-pot
sequential glycosylation reactions, and in both cases, the orthogonal
glycosylations are carried out utilizing catalytic activity of FeCl3. A late
stage TEMPO-mediated regioselective oxidation has been performed to achieve the
required uronic acid motif.
PMID- 28489405
TI - Charge Carrier Relaxation in Different Plasticized PEO/PVDF-HFP Blend Solid
Polymer Electrolytes.
AB - In this article, we report first the effect of concentration of ethylene
carbonate plasticizer on conduction and relaxation of charge carriers in PEO/PVDF
HFP-LiClO4 blend electrolytes. Second, the results for different plasticizers,
such as ethylene carbonate, propylene carbonate, and dimethyle carbonate, on the
conductivity and relaxation in these blend electrolytes are compared. We have
followed a new approach for the analysis of the conductivity data. The frequency
dependent conductivity is analyzed using random free-energy barrier model, taking
into consideration the low frequency polarization effect. The temperature
dependences of the ionic conductivity and the relaxation time obtained from the
model exhibit Vogel-Tammann-Fulcher behavior. Using the scaling of the ac
conductivity spectra it is observed that the relaxation dynamics of charge
carriers in blend electrolytes are independent of temperature but depend on the
nature of plasticizers. The electric modulus is studied using Havriliak-Negami
function for the understanding of ionic relaxation. The modulus data are also
analyzed using nonexponential Kohlrausch-Williams-Watts function. The temperature
dependence of the relaxation time obtained from modulus analysis follows Vogel
Tammann-Fulcher relation for all plasticized electrolytes. It is observed that
the stretched exponent is much lower than unity, which suggests that charge
carrier relaxation is highly nonexponential in these plasticized electrolytes.
PMID- 28489406
TI - Initiation Reactions in Acetylene Pyrolysis.
AB - In gas-phase combustion systems the interest in acetylene stems largely from its
role in molecular weight growth processes. The consensus is that above 1500 K
acetylene pyrolysis starts mainly with the homolytic fission of the C-H bond
creating an ethynyl radical and an H atom. However, below ~1500 K this reaction
is too slow to initiate the chain reaction. It has been hypothesized that instead
of dissociation, self-reaction initiates this process. Nevertheless, rigorous
theoretical or direct experimental evidence is lacking, to an extent that even
the molecular mechanism is debated in the literature. In this work we use
rigorous ab initio transition-state theory master equation methods to calculate
pressure- and temperature-dependent rate coefficients for the association of two
acetylene molecules and related reactions. We establish the role of vinylidene,
the high-energy isomer of acetylene in this process, compare our results with
available experimental data, and assess the competition between the first-order
and second-order initiation steps. We also show the effect of the rapid
isomerization among the participating wells and highlight the need for time-scale
analysis when phenomenological rate coefficients are compared to observed time
scales in certain experiments.
PMID- 28489407
TI - High-Yield Synthesis of Janus Dendritic Mesoporous Silica@Resorcinol-Formaldehyde
Nanoparticles: A Competing Growth Mechanism.
AB - Recently, Janus nanostructures that possess two or more different surface
functions have attracted enormous attention because of their unique structures
and promising applications in diverse fields. In this work, we present that Janus
structured dendritic mesoporous silica@resorcinol-formaldehyde (DMS@RF)
nanoparticles can be prepared through a simple one-pot colloidal method. The
Janus DMS@RF nanoparticle shows a bonsai-like morphology which consists of a
dendritic mesoporous silica part and a spherical RF part. After a systematic
study on the growth process, we proposed a competing growth mechanism that
accounts for the formation of Janus nanostructures. It is believed that suitable
polymerization rate of silica and RF resin is critical. Based on the competing
growth mechanism, eccentric and concentric core-shell nanostructures have been
successfully prepared by tuning the polymerization rates of silica and RF,
respectively. Metal-contained ternary Janus nanoparticles that might be used for
catalysis have also been prepared. This research may pave the way for the
practical applications of delicate nanomaterials with desired structures and
properties.
PMID- 28489408
TI - Thermodynamics and Mechanisms of the Interactions between Ultrasmall Fluorescent
Gold Nanoclusters and Human Serum Albumin, gamma-Globulins, and Transferrin: A
Spectroscopic Approach.
AB - Noble metal nanoclusters (NCs) show great promise as nanoprobes for bioanalysis
and cellular imaging in biological applications due to ultrasmall size, good
photophysical properties, and excellent biocompatibility. In order to achieve a
comprehensive understanding of possible biological implications, a series of
spectroscopic measurements were conducted under different temperatures to
investigate the interactions of Au NCs (~1.7 nm) with three model plasmatic
proteins (human serum albumin (HSA), gamma-globulins, and transferrin). It was
found that the fluorescence quenching of HSA and gamma-globulins triggered by Au
NCs was due to dynamic quenching mechanism, while the fluorescence quenching of
transferrin by Au NCs was a result of the formation of a Au NC-transferrin
complex. The apparent association constants of the Au NCs bound to HSA, gamma
globulins, and transferrin demonstrated no obvious difference. Thermodynamic
studies demonstrated that the interaction between Au NCs and HSA (or gamma
globulins) was driven by hydrophobic forces, while the electrostatic interactions
played predominant roles in the adsorption process for transferrin. Furthermore,
it was proven that Au NCs had no obvious interference in the secondary structures
of these three kinds of proteins. In turn, these three proteins had a minor
effect on the fluorescence intensity of Au NCs, which made fluorescent Au NCs
promising in biological applications owing to their chemical and photophysical
stability. In addition, by comparing the interactions of small molecules, Au NCs,
and large nanomaterials with serum albumin, it was found that the binding
constants were gradually increased with the increase of particle size. This work
has elucidated the interaction mechanisms between nanoclusters and proteins, and
shed light on a new interaction mode different from the protein corona on the
surface of nanoparticles, which will highly contribute to the better design and
applications of fluorescent nanoclusters.
PMID- 28489409
TI - Ultralow Stress, Thermally Stable Cross-Linked Polymer Films of
Polydivinylbenzene (PDVB).
AB - Although closely related to polystyrene, poly(divinylbenzene) (PDVB) has found
limited utility due to the difficulties associated with its synthesis. As a
highly cross-linked polymer, PDVB is infusible and insoluble and thus nearly
impossible to shape into films by either melt or solvent-based processes. Here,
we report the initiated chemical vapor deposition (iCVD) of nearly stress-free,
highly transparent, free-standing films of PDVB up to 25 MUm thick. Films
initially grow under tensile intrinsic stress but become more compressive with
thickness and eventually converge to zero-stress values once they reach >=10 MUm
in thickness. Upon initial heating, the evaporative loss of unreacted monomer
left in the polymer matrix induces between 35 and 45 MPa of tensile stress in the
films. Afterward, subsequent heating cycles induce reversible stress and film
expansion behaviors. We estimate the degree of cross-linking to be 44%, resulting
in high thermal stability (up to 300 degrees C) and mechanical stiffness
(Young's modulus of 5.2 GPa). The low stress combined with high cross-linking
makes iCVD PDVB an excellent candidate for protective coatings in harsh
environments.
PMID- 28489410
TI - Strategically Designing a Pumpless Microfluidic Device on an "Inert"
Polypropylene Substrate with Potential Application in Biosensing and Diagnostics.
AB - This study is an attempt to make a step forward to implement the very immature
concept of pumpless transportation of liquid into a real miniaturized device or
lab-on-chip (LOC) on a plastic substrate. "Inert" plastic materials such as
polypropylene (PP) are used in a variety of biomedical applications but their
surface engineering is very challenging. Here, it was demonstrated that with a
facile innovative wettability patterning route using fluorosilanized UV
independent TiO2 nanoparticle coating it is possible to create wedge-shaped open
microfluidic tracks on inert solid surfaces for low-cost biomedical devices (lab
on-plastic). For the future miniaturization and integration of the tracks into a
device, a variety of characterization techniques were used to not only
systematically study the surface patterning chemistry and topography but also to
have a clear knowledge of its biological interactions and performance. The effect
of such surface architecture on the biological performance was studied in terms
of static/dynamic protein (bovine serum albumin) adsorption, bacterial
(Staphylococcus aureus and Staphylococcus epidermidis) adhesion, cell viability
(using HeLa and MCF-7 cancer cell lines as well as noncancerous human fibroblast
cells), and cell patterning (Murine embryonic fibroblasts). Strategies are
discussed for incorporating such a confined track into a diagnostic device in
which its sensing portion is based on protein, microorganism, or cells. Finally,
for the proof-of-principle of biosensing application, the well-known high
affinity molecular couple of BSA-antiBSA as a biological model was employed.
PMID- 28489411
TI - gCoda: Conditional Dependence Network Inference for Compositional Data.
AB - The increasing quality and the reducing cost of high-throughput sequencing
technologies for 16S rRNA gene profiling enable researchers to directly analyze
microbe communities in natural environments. The direct interactions among
microbial species of a given ecological system can help us understand the
principles of community assembly and maintenance under various conditions.
Compositionality and dimensionality of microbiome data are two main challenges
for inferring the direct interaction network of microbes. In this article, we use
the logistic normal distribution to model the background mechanism of microbiome
data, which can appropriately deal with the compositional nature of the data. The
direct interaction relationships are then modeled via the conditional dependence
network under this logistic normal assumption. We then propose a novel penalized
maximum likelihood method called gCoda to estimate the sparse structure of
inverse covariance for latent normal variables to address the high dimensionality
of the microbiome data. An effective Majorization-Minimization algorithm is
proposed to solve the optimization problem in gCoda. Simulation studies show that
gCoda outperforms existing methods (e.g., SPIEC-EASI) in edge recovery of inverse
covariance for compositional data under a variety of scenarios. gCoda also
performs better than SPIEC-EASI for inferring direct microbial interactions of
mouse skin microbiome data.
PMID- 28489412
TI - Brief review of fluid reasoning: Conceptualization, neurobasis, and applications.
AB - In the early part of the twentieth century the value of nonverbal tests was
initially recognized by Yoakum and Yerkes when they wrote how examinees could
fail a verbal test of general ability because of limited skills in English. When
these examinees were then tested with a nonverbal test of ability, they often
performed well, and therefore this approach avoided "injustice by reason of
relative unfamiliarity with English." Measuring cognitive ability with nonverbal
measures that do not require verbal skills has been supported now for nearly a
century. Research has demonstrated that a person's general ability can be
measured validly and reliably without requiring the student to read, write, or
speak. The neuroanatomical and neuro-anatomical basis for FR is well established
and focuses on the frontal-parietal system, and the use of FR measures is a
common practice. In this brief article the current conceptualization of Fluid
Reasoning (FR) is examined, I suggest how popular used constructs on other common
cognitive tests can be conceptualized as a variant of FR. Then, the general
neuroanatomical substrates and networks are revisited, followed by summarizing
some of the practical scenarios for measuring FR may be useful.
PMID- 28489413
TI - Two year outcomes of poststroke writing and reading disorders.
AB - Poststroke language disorders are frequent and include aphasia, alexia, agraphia,
and acalculia. These disorders refer to an acquired inability to read, write and
calculate. In this study, we evaluated the two year outcomes of writing and
reading disorders in poststroke patients, the natural course, recovery and
mortality. We evaluated all the patients with stroke who were admitted to the
Department of Neurology, University Clinical Centre Tuzla in period of six
months, who developed poststroke alexia, agraphia, acalculia, or different
combinations of these language disorders. Outcome of these patients was evaluated
again after 24 months. For clinical assessment of alexia, agraphia, and acalculia
we used Minnesota Test for Differential Diagnosis of Aphasia. We investigated 59
(30.5%) of 193 stroke patients with alexia, agraphia, acalculia, and
combinations. Outcome of these patients after 24 months was: 37 (62.7%) died, 13
(22%) fully recovered, and 9 (15.3%) of them retained the same disorder or
developed dementia or blindness. Binary logistic regression analysis showed that
patients with combined language disorders had significantly higher mortality. The
main factors influencing language disorders recovery in this study are initial
severity of reading, writing and calculation impairment, age, neglect, and level
of education.
PMID- 28489414
TI - On Proportions of Fit Individuals in Population of Mutation-Based Evolutionary
Algorithm with Tournament Selection.
AB - In this article, we consider a fitness-level model of a non-elitist mutation-only
evolutionary algorithm (EA) with tournament selection. The model provides upper
and lower bounds for the expected proportion of the individuals with fitness
above given thresholds. In the case of so-called monotone mutation, the obtained
bounds imply that increasing the tournament size improves the EA performance. As
corollaries, we obtain an exponentially vanishing tail bound for the Randomized
Local Search on unimodal functions and polynomial upper bounds on the runtime of
EAs on the 2-SAT problem and on a family of Set Cover problems proposed by E.
Balas.
PMID- 28489415
TI - Hepatic Steatosis Accompanies Pulmonary Alveolar Proteinosis.
AB - Maintenance of tissue-specific organ lipid compositions characterizes mammalian
lipid homeostasis. The lungs and liver synthesize mixed phosphatidylcholine (PC)
molecular species that are subsequently tailored for function. The lungs
progressively enrich disaturated PC directed to lamellar body surfactant stores
before secretion. The liver accumulates polyunsaturated PC directed to very-low
density lipoprotein assembly and secretion, or to triglyceride stores. In each
tissue, selective PC species enrichment mechanisms lie at the heart of effective
homeostasis. We tested for potential coordination between these spatially
separated but possibly complementary phenomena under a major derangement of lung
PC metabolism, pulmonary alveolar proteinosis (PAP), which overwhelms homeostasis
and leads to excessive surfactant accumulation. Using static and dynamic
lipidomics techniques, we compared (1) tissue PC compositions and contents, and
(2) in lungs, the absolute rates of synthesis in both control mice and the
granulocyte-macrophage colony-stimulating factor knockout model of PAP.
Significant disaturated PC accumulation in bronchoalveolar lavage fluid, alveolar
macrophage, and lavaged lung tissue occurred alongside increased PC synthesis,
consistent with reported defects in alveolar macrophage surfactant turnover.
However, microscopy using oil red O staining, coherent anti-Stokes Raman
scattering, second harmonic generation, and transmission electron microscopy also
revealed neutral-lipid droplet accumulations in alveolar lipofibroblasts of
granular macrophage colony-stimulating factor knockout animals, suggesting that
lipid homeostasis deficits extend beyond alveolar macrophages. PAP plasma PC
composition was significantly polyunsaturated fatty acid enriched, but the
content was unchanged and hepatic polyunsaturated fatty acid-enriched PC content
increased by 50% with an accompanying micro/macrovesicular steatosis and a
fibrotic damage pattern consistent with nonalcoholic fatty liver disease. These
data suggest a hepatopulmonary axis of PC metabolism coordination, with wider
implications for understanding and managing lipid pathologies in which compromise
of one organ has unexpected consequences for another.
PMID- 28489416
TI - Concordance validity of PVTs in a sample of veterans referred for mild TBI.
AB - Concordance validity of commonly used performance validity tests (PVTs) was
assessed in a sample of Operation Enduring Freedom/Operation Iraqi
Freedom/Operation New Dawn (OEF/OIF/OND) veterans referred to an mTBI screening
clinic in a south-eastern Veterans Affairs hospital. Veteran service members
(total n = 184) completed the Rey-15, Repeatable Battery of the Assessment for
Neuropsychological Status Effort Index (RBANS EI), and Reliable Digit Span (RDS)
from the Wechsler Intelligence Scales. Kappa coefficients and percentage of
agreement were established to determine the level of concordance between the
three measures. PVT failure rate ranged from 7.4% of the sample (Rey-15) to 26.1%
(RBANS EI Liberal). The highest concordance was found between the Rey 15 and
RBANS EI "highly suspicious" cut-off, with the lowest agreement noted between all
PVTs and the RBANS EI "liberal" cut-score. All concordance coefficients fell
within the fair to moderate levels. Overall, the observed agreement between the
explored measures was generally consistent with or greater than other studies of
PVT concordance. Given the rates of concordance, the current results continue to
suggest that PVTs are likely to measure a construct separate from the typical
cognitive domains.
PMID- 28489418
TI - Studies on the Clustering Algorithm for Analyzing Gene Expression Data with a
Bidirectional Penalty.
AB - This article reports a new clustering method based on the k-means algorithm to
high-dimensional gene expression data. The proposed approach makes use of
bidirectional penalties to constrain the number of clusters and centroids of
clusters to simultaneously determine the unknown number of clusters and handle
large amounts of noise in gene expression data. Numeric studies indicate that
this algorithm not only performs better in clustering but is also comparable to
other approaches in its ability to obtain the correct number of clusters and
correct signal features. Finally, we apply the proposed approach to analyze two
benchmark gene expression datasets. These analyses again indicate that the
proposed algorithm performs well in clustering high-dimensional gene expression
data with an unknown number of clusters.
PMID- 28489417
TI - A Semiquantitative Computed Tomographic Grading System for Evaluating Therapeutic
Response in Pulmonary Alveolar Proteinosis.
AB - RATIONALE: A useful semiquantitative method of using computed tomographic (CT)
images to evaluate therapeutic response in pulmonary alveolar proteinosis (PAP)
has not been established, although the extent score or grading score of ground
glass opacities has been used. OBJECTIVES: The purpose of this study was to
establish a semiquantitative method for evaluating therapeutic response in PAP.
METHODS: CT scans were obtained within 1 month before and after therapy from 32
patients with PAP who participated in a multicenter phase II trial of granulocyte
macrophage colony-stimulating factor inhalation therapy. The scans were evaluated
by two chest radiologists independently. Increased parenchymal opacity was
evaluated on the basis of its intensity and extent (CT grade), and the severity
scores were compared with CT scores based on the extent alone (CT extent), as
well as on the basis of physiological and serological results. RESULTS: CT grade
score and CT extent score had significant correlation with diffusing capacity of
the lung for carbon monoxide percent predicted (%DlCO), PaO2, VC percent
predicted (%VC), Krebs von den Lungen (KL)-6, and surfactant protein D. The
change in CT grade score between pre- and post-treatment examinations (DeltaCT
grade) correlated better with difference of PaO2 between pre- and post-treatment
examinations (DeltaPaO2) than DeltaCT extent (difference of CT extent score
between pre- and post-treatment examinations). In univariate analysis, DeltaCT
grade, DeltaCT extent, DeltaKL-6, Delta%DlCO, Delta%VC, and change in surfactant
protein D correlated significantly with DeltaPaO2. In multivariate analysis,
DeltaCT grade and DeltaKL-6 correlated more closely with DeltaPaO2. CONCLUSIONS:
Although a number of CT variables were collected, the currently proposed grading
system that correlates well with PaO2 should be viewed as a retrospective scoring
system that needs future validation with another PAP cohort.
PMID- 28489419
TI - When is a novel psychometric measure needed? A preliminary analysis regarding the
Cognitive Assessment for Stroke Patients (CASP) battery compared with MMSE and
MoCA.
AB - The need for quick tools to sketch an early but accurate cognitive profile of
patients who suffered brain damage or head trauma is of primary importance.
Nonetheless, in the Italian context, the most-diffused screening tools are still
those originally devised to diagnose dementia. The present pilot study then aimed
at investigating the potential and feasibility of a novel screening battery, the
Cognitive Assessment for Stroke Patients (CASP), in a sample of Italian patients
by comparing it to Mini-Mental State Examination (MMSE) and Montreal Cognitive
Assessment (MoCA) tests. A total of 29 neurology patients took part in the study.
Participants underwent a screening procedure including the administration of
MMSE, MoCA, and CASP. Data analysis suggested that the scores of the Italian
version of the CASP are relatively less affected by the presence of language
difficulties-common sequelae of stroke and head traumas-with respect to MMSE and
MoCA ones. Furthermore, CASP scores proved to be highly correlated with both MMSE
and MoCA scores, showing good clinical potential. Finally, the outcomes of
administered tests proved not to be influenced by etiology or gender, and CASP
scores showed a diminishing trend related to patients' age and a positive
association with patients' education.
PMID- 28489420
TI - Anthropologists in MalariaWorld.
AB - The history of anthropological contributions to the study of malaria is reviewed
in terms of three additive phases: (1) cultural-historical analyses; (2) applied
work aimed at the improvement of malaria control programs; and (3) introduction
of critical medical anthropological themes about malaria control. The critical
approaches include themes of the cultural construction of reality-the definition
of "malaria"; political-economic structures in health inequalities; and an
emphasis on social factors as exemplified in the present special issue. The
contemporary culture of malaria researchers and programs-called MalariaWorld-is
described in terms of economy, social organization, and belief system. Five
common features of articles in this special issue are described as unique
anthropological features that are key for understanding MalariaWorld.
PMID- 28489421
TI - Mechanisms and Functions of Spatial Protein Quality Control.
AB - A healthy proteome is essential for cell survival. Protein misfolding is linked
to a rapidly expanding list of human diseases, ranging from neurodegenerative
diseases to aging and cancer. Many of these diseases are characterized by the
accumulation of misfolded proteins in intra- and extracellular inclusions, such
as amyloid plaques. The clear link between protein misfolding and disease
highlights the need to better understand the elaborate machinery that manages
proteome homeostasis, or proteostasis, in the cell. Proteostasis depends on a
network of molecular chaperones and clearance pathways involved in the
recognition, refolding, and/or clearance of aberrant proteins. Recent studies
reveal that an integral part of the cellular management of misfolded proteins is
their spatial sequestration into several defined compartments. Here, we review
the properties, function, and formation of these compartments. Spatial
sequestration plays a central role in protein quality control and cellular
fitness and represents a critical link to the pathogenesis of protein aggregation
linked diseases.
PMID- 28489422
TI - Mechanisms of automaticity and anticipatory control in fluid intelligence.
AB - The constructs of fluid (Gf) and crystalized (Gc) intelligence represent an early
attempt to describe the mechanisms of problem solving in the vertebrate brain.
Modern neuroscience demonstrates that problem solving involves interplay between
the mechanisms of automaticity and anticipatory control, enabling nature's
elegant solution to the challenges animals face in their environment. Studies of
neural functioning are making clear the primary role of cortical-subcortical
interactions in the manifestation of intelligent behavior in humans and other
vertebrates. A tridimensional model of intelligent problem solving is explored,
wherein the basal ganglia system (BGS) and cerebrocerebellar system (CCS)
interact within large scale brain networks. The BGS and CCS work together to
enable automaticity to occur. The BGS enables the organism to learn what to do
through a powerful instrumental learning system. The BGS also regulates when
behavior is released through an inhibitory system which is incredibly sensitive
to context. The CCS enables the organism to learn how to perform adaptive
behaviors. Internal cerebellar models enable gradual improvements in the quality
of behavioral output. The BGS and CCS interact within large scale brain networks,
including the dorsal attention network (DAN), ventral attention network (VAN),
default mode network (DMN) and frontoparietal network (FPN). The interactions of
these systems enable vertebrate organisms to develop a vast array of complex
adaptive behaviors. The benefits and importance of developing clinical tests to
measure the integrity of these systems is considered.
PMID- 28489423
TI - Is rheumatoid arthritis associated with reduced immunogenicity of the influenza
vaccination? A systematic review and meta-analysis.
AB - OBJECTIVE: To determine whether immunogenicity and safety of the influenza
vaccination in rheumatoid arthritis (RA) patients are significantly different
from those in a healthy population. METHODS: PubMed, MEDLINE, Embase, Cochrane
Library and Web of Science were searched on 31 August 2016. Studies were included
when they met the inclusion criteria. Two reviewers independently extracted data
on study characteristics, methodological quality and outcomes. The primary
outcome was seroprotection (SP) rate after immunization. RESULTS: Thirteen
studies were included. The SP rates did not significantly differ between the RA
patients and healthy controls for the H3N2 (RR = 0.96, 95% CI, 0.82 to 1.13, p =
.64) and B strain (RR = 0.95, 95% CI 0.84 to 1. 08, p = .44). Nevertheless, RA
was associated with a significant decrease in SP rate for the H1N1 strain (RR =
0.72, 95% CI 0.60 to 0.86, p < .001). RA patients receiving immunosuppressive
chemotherapy, TNF blockers, rituximab and other biologics responded to the H1N1
strain significantly less than healthy controls in SP rate, whereas those
receiving steroids did not. Non-adjuvanted vaccination had a significantly lower
SP rate than in healthy controls, whereas adjuvanted vaccination did not. RA was
associated with an increase in adverse events (RR = 1.77, 95% CI 1.02 to 3.08, p
= .04). CONCLUSIONS: Immunogenicity was significantly different between RA
patients and healthy controls for the H1N1 strain, but not for the H3N2 or B
strains. Adverse event rates were higher in RA patients. Adjuvant and special
kinds of immunosuppressive biologics may play an important role in immunogenicity
of inactivated influenza vaccines for RA patients.
PMID- 28489424
TI - A novel pH-responsive hydrogel-based on calcium alginate engineered by the
previous formation of polyelectrolyte complexes (PECs) intended to vaginal
administration.
AB - This work aimed to develop a calcium alginate hydrogel as a pH responsive
delivery system for polymyxin B (PMX) sustained-release through the vaginal
route. Two samples of sodium alginate from different suppliers were
characterized. The molecular weight and M/G ratio determined were, approximately,
107 KDa and 1.93 for alginate_S and 32 KDa and 1.36 for alginate_V. Polymer
rheological investigations were further performed through the preparation of
hydrogels. Alginate_V was selected for subsequent incorporation of PMX due to the
acquisition of pseudoplastic viscous system able to acquiring a differential
structure in simulated vaginal microenvironment (pH 4.5). The PMX-loaded hydrogel
(hydrogel_PMX) was engineered based on polyelectrolyte complexes (PECs) formation
between alginate and PMX followed by crosslinking with calcium chloride. This
system exhibited a morphology with variable pore sizes, ranging from 100 to 200
MUm and adequate syringeability. The hydrogel liquid uptake ability in an acid
environment was minimized by the previous PECs formation. In vitro tests
evidenced the hydrogels mucoadhesiveness. PMX release was pH-dependent and the
system was able to sustain the release up to 6 days. A burst release was observed
at pH 7.4 and drug release was driven by an anomalous transport, as determined by
the Korsmeyer-Peppas model. At pH 4.5, drug release correlated with Weibull model
and drug transport was driven by Fickian diffusion. The calcium alginate
hydrogels engineered by the previous formation of PECs showed to be a promising
platform for sustained release of cationic drugs through vaginal administration.
PMID- 28489425
TI - Tissue-specific effects of estrogen on glycerol channel aquaporin 7 expression in
an ovariectomized mouse model of menopause.
AB - OBJECTIVE: Elevated fat mass and redistribution of body fat are commonly observed
in postmenopausal women. Aquaporin 7 (AQP7), a unique glycerol permeable integral
membrane protein, has been associated with the onset of obesity. We hypothesized
that estrogen supplementation could counteract this fat accumulation and
redistribution through tissue-specific modulation of AQP7. METHODS: We measured
fat depot weight, adipocyte size, and the expression of AQP7 and glycerol kinase
(GK) in visceral and subcutaneous fat tissues of ovariectomized mice supplemented
with or without 17beta-estradiol. RESULTS: Removal of the ovaries resulted in a
significant decrease in AQP7 expression and an increase in GK expression in
visceral adipocyte tissue; expression of AQP7 and GK in subcutaneous adipose
tissue remained unaltered. Supplementation with estrogen significantly restored
the visceral, but not subcutaneous, fat depot mass and adipocyte size to those of
sham-operated mice. A marked increase in the expression of AQP7 and a reduction
of GK were observed selectively in the visceral fat depots in estrogen-treated
mice. CONCLUSIONS: Our results suggest that estrogen has tissue-specific effects
on AQP7 expression, and modulation of AQP7 by estrogen alters the balance of
adipocyte metabolism between adipose tissue depots.
PMID- 28489426
TI - Preparation, characterization and in vitro evaluation of microemulsion of
raloxifene hydrochloride.
AB - Raloxifene hydrochloride (RLX) is a selective estrogen receptor modulator which
is orally used for treatment of osteoporosis and prevention of breast cancer. The
drug has low aqueous solubility and bioavailability. The aim of the present study
is to formulate and characterize oil-in-water microemulsion systems for oral
delivery of RLX. To enhance the drug aqueous solubility, microemulsion based on
sesame oil was prepared. Sesame oil and Tween 80 were selected as the drug
solvent oil and surfactant, respectively. In the first and second formulations,
Edible glycerin and Span 80 were applied as co-surfactant, respectively. Pseudo
ternary phase diagrams showed that the best surfactant/co-surfactant ratios in
the first and second formulations were 4:1 and 9:1, respectively. The particle
size of all free drug-loaded and drug loaded samples were in the range of 31.25
+/- 0.3 nm and 60.9 +/- 0.1 nm, respectively. Electrical conductivity coefficient
and refractive index of all microemulsion samples confirmed the formation of oil
in-water type of microemulsion. In vitro drug release profile showed that after
24 hours, 46% and 63% of the drug released through the first formulation in 0.1%
(w/v) Tween 80 in distilled water as a release medium and phosphate buffer
solution (PBS) at pH = 5.5, respectively. These values were changed to 57% and
98% for the second formulation. Results confirmed that the proposed microemulsion
system containing RLX could improve and control the drug release profile in
comparison to conventional dosage form.
PMID- 28489427
TI - Air Pollution from Livestock Farms Is Associated with Airway Obstruction in
Neighboring Residents.
AB - RATIONALE: Livestock farm emissions may not only affect respiratory health of
farmers but also of neighboring residents. OBJECTIVES: To explore associations
between spatial and temporal variation in pollutant emissions from livestock
farms and lung function in a general, nonfarming, rural population in the
Netherlands. METHODS: We conducted a cross-sectional study in 2,308 adults (age,
20-72 yr). A pulmonary function test was performed measuring prebronchodilator
and post-bronchodilator FEV1, FVC, FEV1/FVC, and maximum mid-expiratory flow
(MMEF). Spatial exposure was assessed as (1) number of farms within 500 m and
1,000 m of the home, (2) distance to the nearest farm, and (3) modeled annual
average fine dust emissions from farms within 500 m and 1,000 m of the home
address. Temporal exposure was assessed as week-average ambient particulate
matter <10 MUm in diameter and ammonia (NH3) concentrations before lung function
measurements. Data were analyzed with generalized additive models (smoothing).
MEASUREMENTS AND MAIN RESULTS: A negative association was found between the
number of livestock farms within a 1,000-m buffer from the home address and MMEF,
which was more pronounced in participants without atopy. No associations were
found with other spatial exposure variables. Week-average particulate matter <10
MUm in diameter and NH3 levels were negatively associated with FEV1, FEV1/FVC,
and MMEF. In a two-pollutant model, only NH3 remained associated. A 25-MUg/m3
increase in NH3 was associated with a 2.22% lower FEV1 (95% confidence interval,
3.69 to -0.74), FEV1/FVC of -1.12% (-1.96 to -0.28), and MMEF of -5.67% (-8.80 to
-2.55). CONCLUSIONS: Spatial and temporal variation in livestock air pollution
emissions are associated with lung function deficits in nonfarming residents.
PMID- 28489429
TI - Treatment of Hallucinations in the Context of Anxiety: When Less Is More.
PMID- 28489428
TI - A Single-Molecule View of Genome Editing Proteins: Biophysical Mechanisms for
TALEs and CRISPR/Cas9.
AB - Exciting new advances in genome engineering have unlocked the potential to
radically alter the treatment of human disease. In this review, we discuss the
application of single-molecule techniques to uncover the mechanisms behind two
premier classes of genome editing proteins: transcription activator-like effector
nucleases (TALENs) and the clustered regularly interspaced short palindromic
repeats (CRISPR)/CRISPR-associated system (Cas). These technologies have
facilitated a striking number of gene editing applications in a variety of
organisms; however, we are only beginning to understand the molecular mechanisms
governing the DNA editing properties of these systems. Here, we discuss the DNA
search and recognition process for TALEs and Cas9 that have been revealed by
recent single-molecule experiments.
PMID- 28489430
TI - From the Editor-in-Chief's Desk.
PMID- 28489433
TI - Clinical News.
PMID- 28489432
TI - Touching the elephant: The search for fluid intelligence.
AB - Many constructs that we take for granted in modern neuropsychology, fluid
intelligence among them, can best be explained by conceptionalizing them as a
collection of task specific processes engaged in by an integrated recruited
network involved in problem solving. Fractionalizing the network in an attempt to
describe elements of its function leads to arbitrarily defined segments that may
be interesting to discuss abstractly, but never occur independently in the real
world operation of the system. We will seek to demonstrate that the construct of
fluid intelligence is like that. It is a description of a type of operation of a
network dedicated to solving problems and the composition of the network that is
responsible for the activity changes in a task specific manner. As a result,
fluid intelligence is not an independent skill, or a thing that lives on its own,
or can be measured independently of the other things that contribute to the
overall operation of the network as it seeks to solve problems.
PMID- 28489434
TI - Is training the answer to everything?
PMID- 28489435
TI - Improved emergency department patient care via rapid assessment and triage.
PMID- 28489436
TI - Liver transplantation: post-transplant management.
AB - Medical care for patients following liver transplantation is complex and requires
a holistic approach to management. Patients and clinicians are faced with
multiple challenges: immunosuppressive regimens must be optimized to avoid and
treat graft rejection, the risk and atypical features of sepsis in the
immunocompromised patient must be recognized, steps are required to reduce the
recurrence of liver disease and the long-term increased risks of malignancy,
renal failure and metabolic complications need managing. Despite the benefits of
liver transplantation there are additional concerns regarding the impact upon
quality of life. This review will focus upon the care of patients following liver
transplantation. As these patients will present to a broad range of clinicians,
an understanding of the common drugs used post-transplantation and general
approach to management of these patients will be of benefit to the general
clinical audience.
PMID- 28489437
TI - Putting the mouth back into the body.
PMID- 28489438
TI - Surgical issues in retrieval and implantation.
AB - With increasing demand for organ transplantation and patients deteriorating or
dying on the waiting list, organs are now being increasingly used from donors
previously considered too marginal. This requires improvements to donor
management during the retrieval process, and of the organ during transport and
subsequent implantation, in order to maintain outcomes.
PMID- 28489439
TI - Assessment of haemodynamic disturbance.
PMID- 28489440
TI - Optimizing a career in surgery.
PMID- 28489441
TI - Treatment of haemodynamic disturbance.
PMID- 28489442
TI - How not to miss major spinal pathology in patients with back pain.
PMID- 28489444
TI - Noise-induced hearing loss: a modern epidemic?
AB - Hearing loss is an increasingly common problem in the UK, and noise-induced
hearing loss is the second most common acquired cause. There is a greater burden
on the younger population, as recreational noise exposure is an important
contributor. New damaging hearing behaviours have emerged including loud music
exposure at concerts, nightclubs and via personal music players. The mechanism of
damage is thought to involve many diverse pathways, which include oxidative
damage, mechanical shearing forces and glutamate excitotoxicity. Although no
current treatment exists to reverse the damage caused, these pathways can be
targeted by agents that are being trialled for use in post-exposure treatment and
prevention, with conflicting results. Other preventative strategies are important
in addressing damaging hearing behaviours, including 'safe listening' promotion
with advocacy materials for young adults, and promoting safe listening devices.
PMID- 28489445
TI - Mucosal malignant melanoma presenting with huge, fleshy, dark-red polyp in the
nasal cavity.
PMID- 28489446
TI - Liver transplantation: need, indications, patient selection and pre-transplant
care.
AB - Chronic or acute liver failure and primary liver cancers can be effectively
managed with liver transplantation. The range of indications for liver
transplantation is increasing but there is a mismatch between the numbers of
available donations and current needs. Specific criteria for listing patients
exist but, at minimum, the predicted mortality without transplantation must
exceed that with transplantation, coupled with a 50% predicted 5-year survival
following liver transplantation. The risk posed by liver disease must be weighed
against the risk of liver transplantation, considering the patient's
comorbidities, age, nutritional status and behavioural factors in a complex
assessment process. This article reviews current UK practice in the selection and
care of patients being assessed for liver transplantation.
PMID- 28489447
TI - Patient-initiated splintage of a mallet finger injury avoids unnecessary
complications.
PMID- 28489448
TI - Immediate postoperative management and complications on the intensive care unit.
AB - The postoperative management of patients immediately after liver transplantation
requires knowledge of this complex surgery and the physiology that accompanies
liver failure. A multidisciplinary approach to the care of these patients is
essential in order to reduce postoperative complications and preserve function in
the transplanted organ. By their nature, patients undergoing liver
transplantation have complicated medical problems before surgery which must be
borne in mind when managing them after surgery. Haemorrhage, haemodynamic
instability, acute renal failure, hepatic artery thrombosis and primary graft non
function are some of the complications that clinicians must be prepared for in
the first days after transplantation. Pre-empting complications and acting
rapidly to overt them is likely to have a considerable positive impact in these
patients.
PMID- 28489449
TI - Progressive respiratory failure: a rare complication after graded talc
pleurodesis.
PMID- 28489450
TI - Anaesthesia for liver transplantation.
AB - Liver transplantation is a complex procedure that requires a truly
multidisciplinary team approach with anaesthetic involvement from the outset in
order to ensure excellent outcomes. Before a patient is placed on the waiting
list for a liver transplant, a thorough evaluation is undertaken and his/her
suitability for transplantation discussed in a patient selection committee
meeting. The perioperative management of patients requiring transplantation can
be challenging because of the systemic implications of liver disease, approaches
to surgical technique and the quality of the grafts used; an increase in the use
of marginal donor organs to meet the organ demand poses its own unique
difficulties.
PMID- 28489451
TI - Late presentation of ischaemic monomelic neuropathy after vascular access
surgery.
PMID- 28489452
TI - Medicine at war a century ago.
PMID- 28489454
TI - Acquisition and Transmission of Streptococcus pneumoniae Are Facilitated during
Rhinovirus Infection in Families with Children.
AB - RATIONALE: Laboratory and clinical evidence suggests synergy between rhinoviruses
and Streptococcus pneumoniae in the pathogenesis of respiratory tract infections.
However, it is unclear whether rhinoviruses promote pneumococcal acquisition and
transmission. OBJECTIVES: To describe the impact of rhinovirus infection on the
acquisition and transmission of pneumococci within families with children.
METHODS: We investigated 29 families with at least two children. The follow-up
started at the onset of respiratory infectious symptoms in any family member and
consisted of daily symptom diary and nasal swab samples from each participant
twice per week for 3 weeks. Swabs were taken by the parents and sent to a study
clinic by mail. Rhinoviruses were detected by reverse transcription-polymerase
chain reaction and typed by sequencing. Pneumococci were identified by an antigen
test and by standard culture methods, serotyping, and whole-genome sequencing.
The effect of rhinovirus infection on the rates of pneumococcal acquisition and
within-family transmission was estimated from the observed acquisition events and
person-times spent uncolonized, using Poisson regression. MEASUREMENTS AND MAIN
RESULTS: Rhinovirus was detected in 38 subjects (30%) at the onset and in 86
subjects (67%) during the follow-up. S. pneumoniae was detected on the first day
in 9 (7%) and during follow-up in 38 (30%) subjects. Children with rhinovirus
infection had a 4.3-fold rate of pneumococcal acquisition from the community (95%
confidence interval, 1.1-15.4) and a 14.8-fold rate of within-family transmission
(95% confidence interval, 3.1-69.6) compared with children without rhinovirus
infection. CONCLUSIONS: Rhinovirus infection within families facilitates
acquisition and within-family transmission of S. pneumoniae.
PMID- 28489455
TI - MicroRNA Profiling in Asthma: Potential Biomarkers and Therapeutic Targets.
AB - Asthma is a heterogeneous chronic inflammatory disorder in which different
endotypes contribute to define clinical inflammatory phenotypes. MicroRNAs
(miRNAs) are a group of minute, endogenous 22-25 nt RNA elements that join to
particular mRNAs to reduce translation and increase messenger RNA degradation.
miRNAs operate in post-transcriptional control and regulate physiological and
pathological processes in several illnesses. The purpose of this work is to
review and discuss the current knowledge about the function of miRNAs in asthma,
focusing particularly on their biological properties, pathophysiologic actions,
and possible use as markers and treatments for asthma.
PMID- 28489453
TI - Association of Decision-making with Patients' Perceptions of Care and Knowledge
during Longitudinal Pulmonary Nodule Surveillance.
AB - RATIONALE: Patient participation in medical decision-making is widely advocated,
but outcomes are inconsistent. OBJECTIVES: We examined the associations between
medical decision-making roles, and patients' perceptions of their care and
knowledge while undergoing pulmonary nodule surveillance. METHODS: The study
setting was an academically affiliated Veterans Affairs hospital network in which
121 participants had 319 decision-making encounters. The Control Preferences
Scale was used to assess patients' decision-making roles. Associations between
decision-making, including role concordance (i.e., agreement between patients'
preferred and actual roles), shared decision-making (SDM), and perceptions of
care and knowledge, were assessed using logistic regression and generalized
estimating equations. RESULTS: Participants had a preferred role in 98% of
encounters, and most desired an active role (shared or patient controlled). For
some encounters (36%), patients did not report their actual decision-making role,
because they did not know what their role was. Role concordance and SDM occurred
in 56% and 26% of encounters, respectively. Role concordance was associated with
greater satisfaction with medical care (adjusted odds ratio [Adj-OR], 5.39; 95%
confidence interval [CI], 1.68-17.26), higher quality of patient-reported care
(Adj-OR, 2.86; 95% CI, 1.31-6.27), and more disagreement that care could be
better (Adj-OR, 2.16; 95% CI, 1.12-4.16). Role concordance was not associated
with improved pulmonary nodule knowledge with respect to lung cancer risk (Adj
OR, 1.12; 95% CI, 0.63-2.00) or nodule information received (Adj-OR, 1.13; 95%
CI, 0.31-4.13). SDM was not associated with perceptions of care or knowledge.
CONCLUSIONS: Among patients undergoing longitudinal nodule surveillance, a
majority had a preference for having active roles in decision-making.
Interestingly, during some encounters, patients did not know what their role was
or that a decision was being made. Role concordance was associated with greater
patient-reported satisfaction and quality of medical care, but not with improved
knowledge. Patient participation in decision-making may influence perceptions of
care; however, clinicians may need to focus on other communication strategies or
domains to improve patient knowledge and health outcomes.
PMID- 28489456
TI - Expired antivenom: good efficacy in a severely envenomed cat bitten by Sistrurus
miliarius miliarius (Carolina Pigmy Rattlesnake).
PMID- 28489457
TI - Adverse events associated with a large dose of intravenous lipid emulsion for
suspected local anesthetic toxicity.
AB - BACKGROUND: Intravenous lipid emulsion (ILE) has gained favor as a rescue
treatment for cardiovascular collapse due to intravenous local anesthetic
overdose, however, goals of ILE therapy are still being defined. We describe a
case of a girl given 66 mL/kg of 20% lipid emulsion (ILE) in the treatment of
presumed mepivacaine toxicity. CASE REPORT: An 11-year-old girl weighing 55.6 kg
developed pallor, rolling back of the eyes, and rhythmic muscle twitching after
receiving a mandibular nerve block injection with a 1.8 mL ampule of 3%
mepivacaine. With concern for persistent seizures she was given three 1 mL/kg
boluses of ILE, followed by an infusion of 0.25 mL/kg/min. The total dose
ultimately administered was 3670 mL (66 mL/kg) over 7 h. A serum triglyceride
concentration, drawn 2 h after cessation of ILE infusion, was estimated to be
16,583 mg/dL (429 mmol/L) after several dilutions; her blood was grossly lipemic.
Notable signs included hypersomnolence, tachypnea, and tachycardia. Other
complications included apparent metabolic acidosis (serum bicarbonate of 5
mmol/L) with hyperlactatemia (lactate 7.0 mmol/L), difficulty with serum
laboratory interpretation, and a non-contrast brain magnetic resonance imaging
showing high signal in the dural venous sinuses. The lipemia cleared over three
days and the patient recovered uneventfully. Case discussion: This case
demonstrates a unique neurologic and metabolic toxicity associated with ILE given
as an antidote in a high total dose, and highlights the need for cautious
antidotal application of lipid emulsion infusions. Until more data is available,
clinicians are advised to take great care if considering a dose in excess of 12.5
mL/kg/day, the maximum daily dosage recommended by the U.S. Food and Drug
Administration for nutritional supplementation. Careful monitoring of total doses
administered across institutions and hospital wards during transfers is paramount
to avoid inadvertent overdose of antidotes.
PMID- 28489458
TI - Toxicokinetics of ibogaine and noribogaine in a patient with prolonged multiple
cardiac arrhythmias after ingestion of internet purchased ibogaine.
AB - BACKGROUND: Ibogaine is an agent that has been evaluated as an unapproved anti
addictive agent for the management of drug dependence. Sudden cardiac death has
been described to occur secondary to its use. We describe the clinical effects
and toxicokinetics of ibogaine and noribogaine in a single patient. For this
purpose, we developed a LC-MS/MS-method to measure ibogaine and noribogaine
plasma-concentrations. We used two compartments with first order absorption. CASE
DETAILS: The maximum concentration of ibogaine was 1.45 mg/L. Our patient
developed markedly prolonged QTc interval of 647ms maximum, several multiple
cardiac arrhythmias (i.e., atrial tachycardia and ventricular tachycardia and
Torsades des Pointes). QTc-prolongation remained present until 12 days after
ingestion, several days after ibogaine plasma-levels were low, implicating
clinically relevant noribogaine concentrations long after ibogaine had been
cleared from the plasma. The ratio k12/k21 for noribogaine was 21.5 and 4.28 for
ibogaine, implicating a lower distribution of noribogaine from the peripheral
compartment into the central compartment compared to ibogaine. CONCLUSIONS: We
demonstrated a linear relationship between the concentration of the metabolite
and long duration of action, rather than with parent ibogaine. Therefore, after
(prolonged) ibogaine ingestion, clinicians should beware of long-term effects due
to its metabolite.
PMID- 28489459
TI - Corrigendum.
PMID- 28489460
TI - A preliminary study in the alterations of mitochondrial respiration in patients
with carbon monoxide poisoning measured in blood cells.
AB - OBJECTIVES: Carbon monoxide (CO) is a colorless and odorless gas responsible for
poisoning mortality and morbidity in the United States. At this time, there is no
reliable method to predict the severity of poisoning or clinical prognosis
following CO exposure. Whole blood cells, such as peripheral blood mononuclear
cells (PBMCs) and platelets, have been explored for their potential use to act as
sensitive biomarkers for mitochondrial dysfunction which may have a role in CO
poisoning. DESIGN: The objective of this study was to measure mitochondrial
respiration using intact cells obtained from patients exposed to CO as a
potential biomarker for mitochondrial inhibition with results that can be
obtained in a time frame useful for guiding clinical care. This was a
prospective, observational pilot study performed from July 2015 to July 2016 at a
single academic tertiary care center that is the location of the region's only
multi chamber hyperbaric. MEASUREMENTS: Clinical characteristics, patient
demographics, mitochondrial respiration and outcomes were recorded. MAIN RESULTS:
There were 7 patients enrolled with a mean COHb level 26.8 +/- 10 and with a mean
lactate of 1.1 +/- 0.4 mmol/L. All 7 CO exposures were related to heat generators
used during winter months with two deaths. There was a positive correlation
between maximal respiration and COHb levels with both high maximal respiration
and high spare respiratory capacity correlating with a high COHb level. There was
a subset of PBMCs (n = 4) that were analyzed for Complex IV (cytochrome c
oxidase) activity. CONCLUSIONS: In this pilot study, measurements can be
performed in an appropriate timeline for clinical care with potential to serve as
a prognostic marker. Further work is necessary to develop high-resolution
respirometry as a clinical tool for assessing the severity of illness and guiding
therapy.
PMID- 28489461
TI - Estimating the impact of adopting the revised United Kingdom acetaminophen
treatment nomogram in the U.S. population.
AB - BACKGROUND: Acetaminophen toxicity is common in clinical practice. In recent
years, several European countries have lowered the treatment threshold, which has
resulted in increased number of patients being treated at a questionable clinical
benefit. OBJECTIVE: The primary objective of this study is to estimate the cost
and associated burden to the United States (U.S.) healthcare system, if such a
change were adopted in the U.S. METHODS: This study is a retrospective review of
all patients age 14 years or older who were admitted to one of eight different
hospitals located throughout the U.S. with acetaminophen exposures during a five
and a half year span, encompassing from 1 January 2008 to 30 June 2013. Those
patients who would be treated with the revised nomogram, but not the current
nomogram were included. The cost of such treatment was extrapolated to a national
level. RESULTS: 139 subjects were identified who would be treated with the
revised nomogram, but not the current nomogram. Extrapolating these numbers
nationally, an additional 4507 (95%CI 3641-8751) Americans would be treated
annually for acetaminophen toxicity. The cost of lowering the treatment threshold
is estimated to be $45 million (95%CI 36,400,000-87,500,000) annually.
CONCLUSIONS: Adopting the revised treatment threshold in the U.S. would result in
a significant cost, yet provide an unclear clinical benefit.
PMID- 28489462
TI - Response to Juurlink letter: comment on Shively et al. "Acute salicylate
poisoning: risk factors for severe outcome".
PMID- 28489463
TI - Comment on Shively et al. "Acute salicylate poisoning: risk factors for severe
outcome".
PMID- 28489464
TI - Results of a randomized controlled pilot trial of intravascular renal denervation
for management of treatment-resistant hypertension.
AB - OBJECTIVE: Previous trials of catheter-based renal-artery denervation (RDN) as
treatment modality in resistant hypertension (rHT) generated unconvincing
results. In the Investigator-Steered Project on Intravascular Denervation for
Management of Treatment-Resistant Hypertension (INSPiRED; NCT01505010), we
optimized selection and management of rHT patients. METHODS: With ethical
clearance to randomize 18 patients, three Belgian hypertension centers screened
29 rHT patients on treatment with >=3 drugs, of whom 17 after optimization of
treatment (age <70 years; systolic/diastolic office blood pressure (BP) >= 140/90
mm Hg; 24-h BP >=130/80 mm Hg; glomerular filtration rate [eGFR] >= 45
mL/min/1.73 m2; body mass index <40kg/m2) were randomized and 15 were analyzed 6
months later, while medical treatment was continued (n = 9) or combined with RDN
by the EnligHTNTM multi-electrode system (n = 6). RESULTS: The baseline-adjusted
between-group differences amounted to 19.5/10.4 mm Hg (change in control vs.
intervention group, +7.6/+2.2 vs. -11.9/-8.2 mm Hg; P = .088) for office BP,
22.4/13.1 mm Hg (+0.7/+0.3 vs. -21.7/-12.8; mm Hg; P <= .049) for 24-h BP, the
primary efficacy endpoint, and 2.5 mL/min/1.73 m2 (+1.5 vs. -1.1 mL/min/1.73 m2;
P = .86) for eGFR, the primary safety endpoint. At 6 month, ECG voltages and the
number of prescribed drugs (P <= .036) were lower in RDN patients, but quality of
life and adherence, captured by questionnaire and urine analysis were similar in
both groups. Changes in BP and adherence were unrelated. No major complications
occurred. CONCLUSIONS: The INSPiRED pilot suggests that RDN with the EnligHTNTM
system is effective and safe and generated insights useful for the design of
future RDN trials.
PMID- 28489465
TI - Effects of phototherapy plus physical training on metabolic profile and quality
of life in postmenopausal women.
AB - A cluster of metabolic abnormalities are markedly higher among postmenopausal
women. The present study evaluated the effects of infrared light emitting diode
(LED) during treadmill training on multiple metabolic markers, body fat, dietary
habits and quality of life in postmenopausal women. Forty-five postmenopausal
women aged 50-60 years were randomly assigned to one of three groups, and of
these, 30 women successfully completed the full study. The three groups were as
follows: (i) the LED group, which performed treadmill training associated with
phototherapy (n = 10); (ii) the exercise group, which carried out treadmill
training only (n = 10); and (iii) the sedentary group, which neither performed
physical training nor underwent phototherapy (n = 10). Training was performed
over a period of six months, twice a week for 45 min per session at 85-90% of
maximal heart rate (HRmax), which was obtained during a progressive exercise
testing. The average HR and velocity during treadmill training were 144 +/- 9 bpm
and 5.8 +/- 1.3 km/h for both trained groups. The irradiation parameters were 100
mW, 39 mW/cm2 and 108 J/cm2 for 45 min. Anthropometric data, skinfolds thickness,
biochemical exams (lipid profile, glucose and insulin levels), dietary habits and
quality of life were evaluated. The sum of skinfolds significantly improved in
the exercise and sedentary groups (p < 0.05). Additionally, there was an
improvement in lipid profile, particularly, total cholesterol and low-density
lipoprotein, which reduced significantly for all groups (p ? 0.05). However,
intake of saturated fats was significantly reduced in the sedentary group only (p
< 0.05). The quality of life improved in the LED group only, with a significant
reduction in the total WHQ score (p < 0.05). Physical training with or without
phototherapy may improve the metabolic profile. In addition, phototherapy
together with treadmill training prevented an increase in subcutaneous fat and
facilitated an improved quality of life in postmenopausal women.
PMID- 28489466
TI - Intrathecal Injection of Gadobutrol: A Tale of Caution.
AB - In the field of interventional pain medicine a radiocontrast agent is commonly
used in conjunction with fluoroscopy. Limited work has been published regarding
the use of gadolium based contrast agents (GBCA) in the intrathecal space. We
report a case of an intrathecal gadobutrol injection resulting in neurotoxic
manifestations.A 60-year-old female with a history significant for lumbar post
laminectomy syndrome and intrathecal drug delivery implantation was admitted for
lumbar fusion and kyphoplasty. Postoperatively, the patient had escalating pain
medication requirements. A pump and intrathecal catheter contrast study was
completed to assess the integrity and proper placement of the intrathecal
catheter. Due to patient.s allergy to iodinated contrast, the physician requested
gadolinium contrast dye. Unknown to the staff was that Magnevist had recently
been replaced with an alternative GBCA, Gadavist (gadobutrol). 2 cc of Gadavist
was injected. The catheter was determined to be intact and in proper position.
Less than five minutes after the injection of gadobutrol, the patient reported
spastic pain of the lower extremities. There is a lack of evidence as it relates
to the use of GBCA specifically gadobutrol in the intrathecal space. The use of
gadobutrol in the intrathecal space should be used with caution.
PMID- 28489467
TI - Use of opioid substitution therapies in the treatment of opioid use disorder:
results of a UK cost-effectiveness modelling study.
AB - AIMS: This study investigated the cost-effectiveness of buprenorphine maintenance
treatment (BMT) and methadone maintenance treatment (MMT) vs no opioid
substitution therapy (OST) for the treatment of opioid use disorder, from the UK
National Health Service (NHS)/personal social services (PSS) and societal
perspectives over 1 year. METHODS: Cost-effectiveness of OST vs no OST was
evaluated by first replicating and then expanding an existing UK health
technology assessment model. The expanded model included the impact of OST on
infection rates of human immunodeficiency virus (HIV) and hepatitis C virus (HCV)
infection. RESULTS: Versus no OST, incremental cost-effectiveness ratios (ICERs)
for BMT and MMT were L13,923 and L14,206 per quality-adjusted life year (QALY),
respectively, from a NHS/PSS perspective. When total costs (NHS/PSS and societal)
are considered, there are substantial savings associated with adopting OST; these
savings are in excess of L14,032 for BMT vs no OST and L17,174 for MMT vs no OST
over 1 year. This is primarily driven by a reduction in victim costs. OST
treatment also impacted other aspects of criminality and healthcare resource use.
LIMITATIONS: The model's 1-year timeframe means long-term costs and benefits, and
the influence of changes over time are not captured. CONCLUSIONS: OST can be
considered cost-effective vs no OST from the UK NHS/PSS perspective, with a cost
per QALY well below the UK's willingness-to-pay threshold. There were only small
differences between BMT and MMT. The availability of two or more cost-effective
options is beneficial to retaining patients in OST programs. From a societal
perspective, OST is estimated to save over L14,032 and L17,174 per year for BMT
and MMT vs no OST, respectively, due to savings in victim costs. Further work is
required to fully quantify the clinical and health economic impacts of different
OST formulations and their societal impact over the long-term.
PMID- 28489468
TI - Best dilution of the best corticosteroid for intralesional injection in the
treatment of localized alopecia areata in adults.
AB - PURPOSE: To evaluate and compare the clinical efficacy, dermoscopic results and
safety of triamcinolone acetonide (TA) and betamethasone dipropionate (BD)
injections at different concentrations in localized scalp and beard alopecia.
METHODS: Intralesional injection of BD or TA in three different dilutions; 1/4,
1/8, 1/12 (BD1, BD2, BD3, TA1, TA2, TA3) and Saline (control) was randomly
applied to a total of 231 alopecia patches in 83 patients every four weeks in a
maximum of six sessions until a hair regrowth score of 4 was achieved. The number
of required sessions, sixth-month hair regrowth scores, treatment success rates
and dermoscopic data were investigated. RESULTS: The mean number of required
sessions were similar and significantly lower in BD1 and TA1 being 4.21 +/- 1.12
and 3.74 +/- 0.99, respectively. Dermoscopic examinations revealed similar
terminal hair growth rations in Saline (30.3%), BD1 (44.4%) and TA1 (42.9%).
However, sixth-month hair regrowth scores, overall treatment success rates and
percentage of terminal hair regrowth were similar in BD1 and TA1. However,
adverse effects were more common in TA groups (24.3%) than in BD groups (10.6%)
at the sixth month. CONCLUSIONS: BD 1/4 dilution (1.25 mg/dL) seems best
corticosteroid for intralesional injection in the treatment of localized alopecia
areata in adults.
PMID- 28489469
TI - Significant sE-Selectin levels reduction after 6 months of anti-TNF-alpha therapy
in non-diabetic patients with moderate-to-severe psoriasis.
AB - PURPOSE: Psoriasis patients have high risk of atherosclerosis, characterized by
endothelial dysfunction. We aimed to study the association of the endothelial
activation biomarkers monocyte chemoattractant protein 1 (MCP-1), soluble (s) E
selectin and P-selectin with disease activity and severity in psoriasis patients
treated with anti-TNF-alpha therapy. Also, to evaluate the relationship of
metabolic syndrome features with these biomarkers and the effect of anti-TNF
alpha therapy on these molecules. METHODS: Twenty-nine consecutive non-diabetic
patients with moderate-to-severe psoriasis who underwent 6 months of anti-TNF
alpha-adalimumab therapy were studied. Metabolic and clinical evaluation was
performed prior to anti-TNF-alpha treatment (time 0) and 6 months later. MCP-1,
sE-selectin and sP-selectin serum levels were determined by ELISA. RESULTS:
Dyslipidemic and obese patients showed higher MCP-1 levels at month 6 from the
onset of anti-TNF-alpha therapy (p = .05 and .01, respectively). sE-selectin
positively correlated with pro-inflammatory molecules such as asymmetric
dimethylarginine, sP-selectin and resistin at baseline and month 6 (p < .05). sE
selectin levels significantly reduced after 6 months of therapy (p = .0006).
CONCLUSIONS: Metabolic syndrome features are associated with endothelial
activation in patients with moderate-to-severe psoriasis. Adalimumab therapy led
to a reduction in sE-selectin levels, supporting the beneficial effect of anti
TNF-alpha therapy on mechanisms associated with the development of
atherosclerosis in psoriasis.
PMID- 28489471
TI - Effect of the 2011 Revisions to the Field Triage Guidelines on Under- and Over
Triage Rates for Pediatric Trauma Patients.
AB - BACKGROUND: In 2011, revised Field Triage Guidelines were released jointly by the
Centers for Disease Control and Prevention (CDC) and the American College of
Surgeons - Committee on Trauma (ACS-COT). It is unknown how the modifications
will affect the number of injured children identified by EMS providers as needing
transport to a trauma center. OBJECTIVE: To determine the change in under- and
over-triage rates when the 2011 Field Triage Guidelines are compared to the 2006
and 1999 versions. METHODS: EMS providers in charge of care for injured children
(<15 years) transported to pediatric trauma centers in 3 mid-sized cities were
interviewed immediately after completing transport. Patients were included
regardless of injury severity. The interview included patient demographics and
each criterion from the Field Triage Guidelines' physiologic status, anatomic
injury, and mechanism of injury steps. Included patients were followed through
hospital discharge. The 1999, 2006, and 2011 Guidelines were each retrospectively
applied to the collected data. Children were considered to have needed a trauma
center if they had non-orthopedic surgery within 24 hours, ICU admission, or
died. Data were analyzed using descriptive statistics. RESULTS: EMS interviews
were conducted for 5,610 children and outcome data was available for 5,594
(99.7%). Average age was 7.6 years; 5% of children were identified as needing a
trauma center using the study outcome. Applying the 1999, 2006, or 2011
Guidelines to the EMS interview data the over-triage rate was 32.6%, 27.9%, and
28.0%, respectively. The under-triage rate was 26.5%, 35.1%, and 34.8%,
respectively. The 2011 Guidelines resulted in an 8.2% (95% CI 0.6-15.9%) absolute
increase in under-triage and a 4.6% (95% CI 2.8-6.3%) decrease in over-triage
compared to 1999 Guidelines. CONCLUSION: Use of the Field Triage Guidelines for
children resulted in an unacceptably high rate of under-triage regardless of the
version used. Use of the 2011 Guidelines increased under-triage compared to the
1999 version. Research is needed to determine how to better assist EMS providers
in identifying children who need the resources of a trauma center.
PMID- 28489472
TI - Enalapril maleate orally disintegrating tablets: tableting and in vivo evaluation
in hypertensive rats.
AB - The aim of this study was to develop orally disintegrating tablets (ODTs) for
enalapril maleate (EnM) to facilitate its administration to the elderly or other
patients having dysphagia. Compatibility between EnM and various excipients was
studied using differential scanning calorimetry. ODTs of EnM were prepared by
direct compression of EnM mixtures with various superdisintegrants. The tablets
were evaluated for physical properties including drug content, hardness,
friability, disintegration time, wetting time, and drug release. The
antihypertensive effect of the optimum EnM ODTs was evaluated in vivo in
hypertensive rats and compared with commercial EnM formulation. EnM ODTs had
satisfactory results in terms of drug content and friability. Tablet wetting and
disintegration were fast and dependent on the used superdisintegrant where
croscarmellose showed the fastest wetting and disintegration time of ~7 s. EnM
release from the tablets was rapid where complete release was obtained in 10-15
min. Selected EnM ODTs rapidly and efficiently reduced the rat's blood pressure
to its normal value within 1 h, compared with 4 h for EnM commercial formulation.
These results confirm that EnM ODTs could find application in the management of
hypertension in the elderly or other patients having dysphagia.
PMID- 28489470
TI - Reaction products of hexamethylene diisocyanate vapors with "self" molecules in
the airways of rabbits exposed via tracheostomy.
AB - 1. Hexamethylenediisocyanate (HDI) is a widely used aliphatic diisocyanate and a
well-recognized cause of occupational asthma. 2. "Self" molecules
(peptides/proteins) in the lower airways, susceptible to chemical reactivity with
HDI, have been hypothesized to play a role in asthma pathogenesis and/or chemical
metabolism, but remain poorly characterized. 3. This study employed unique
approaches to identify and characterize "self" targets of HDI reactivity in the
lower airways. Anesthetized rabbits free breathed through a tracheostomy tube
connected to chambers containing either, O2, or O2 plus ~200 ppb HDI vapors.
Following 60 minutes of exposure, the airways were lavaged and the fluid was
analyzed by LC-MS and LC-MS/MS. 4. The low-molecular weight (<3 kDa) fraction of
HDI exposed, but not control rabbit bronchoalveolar lavage (BAL) fluid identified
783.26 and 476.18 m/z [M+H]+ ions with high energy collision-induced dissociation
(HCD) fragmentation patterns consistent with bis glutathione (GSH)-HDI and
mono(GSH)-HDI. Proteomic analyses of the high molecular weight (>3 kDa) fraction
of exposed rabbit BAL fluid identified HDI modification of specific lysines in
uteroglobin (aka clara cell protein) and albumin. 5. In summary, this study
utilized a unique approach to chemical vapor exposure in rabbits, to identify HDI
reaction products with "self" molecules in the lower airways.
PMID- 28489473
TI - Treatment of recalcitrant plantar warts with long-pulsed Nd:YAG laser versus
cantharidin-podophylline resin-salicylic acid.
AB - BACKGROUND: Treatment for recalcitrant plantar warts remains a continuing
challenge as the options for treatment have differing levels of success. long
pulsed Nd:YAG laser is considered a good treatment modality in resistant plantar
warts. On the other hand, high cure rates have been reported with a topical
proprietary formulation consisting of 1% cantharidin, 5% podophyllotoxin, 30%
salicylic acid. AIM: To compare the efficacy of 1% cantharidin, 20% podophylline
resin and 30% salicylic acid (CPS) versus long-pulsed Nd:YAG laser in the
treatment of recalcitrant plantar warts. METHODS: This study included 30 patients
with single or multiple recalcitrant plantar warts; patients were assigned to two
groups: the first group included 15 patients with 71 recalcitrant plantar warts
who were treated by long-pulsed Nd:YAG laser (group I) and the second group
included 15 patients with 78 recalcitrant plantar warts who received CPS (group
II). The diagnosis of plantar warts was made by clinical examination. RESULTS:
Fourteen patients (93%) were completely cleared of their warts with topical CPS,
while 11 patients (73%) showed complete clearance with long-pulsed Nd:YAG laser
with statistically significant difference between the two groups. CONCLUSION:
Topical CPS is safe and efficacious and represents a promising therapeutic
modality than long-pulsed Nd:YAG laser in the treatment of recalcitrant plantar
warts.
PMID- 28489474
TI - Global Burden of Sugar-Related Dental Diseases in 168 Countries and Corresponding
Health Care Costs.
AB - Oral diseases such as dental caries, edentulism (tooth loss), periodontal disease
(PD), and oral cancer currently constitute an increased major public health
burden across the globe, with significant differences between countries. One of
the main drivers of caries, edentulism, and PD is the excessive intake of sugars.
Here, we aimed to quantify the global sugar-related dental health and cost burden
in the year 2010. This study used a health-econometrical model to calculate the
disease burden as well as the direct and indirect costs attributable to the
intake of free sugars (mono- and disaccharides [MDS]). To this end, several
databases from the Institute for Health Metrics and Evaluation (IHME),
Organisation for Economic Co-operation and Development (OECD), Food and
Agriculture Organization (FAO), and World Bank were used. In total, the
corresponding disease burden in 168 countries and economic burden in 31 OECD
countries were quantified. In 2010, the consumption of MDS was associated with a
global dental disease burden of 4.1 million disability-adjusted life years
(DALYs; 95% uncertainty interval [UI]: 2.1 to 7.4 million DALYs), with 2.7
million DALYs from MDS-related caries and 1.4 million DALYs from PD. In terms of
economic costs, MDS-related dental diseases were associated with a global
financial burden of 172 billion US dollars (USD; 95% UI: 91 to 295 billion USD),
the largest share of which (151 billion USD) was incurred in OECD countries.
Overall, 26.3% (95% UI: 13.3% to 47.5%) of the total global oral disease burden
was attributed to the consumption of MDS. The present study emphasizes the need
to further address the role of free sugars in oral health and nutrition policy.
Although the largest share of the economic burden was accounted for by OECD
countries, emerging economies should address this challenge early on in national
public health policies if they are to avoid disease and the prospect of increased
cost burdens.
PMID- 28489475
TI - Antithrombotic strategies for preventing long-term major adverse cardiovascular
events in patients with non-valvular atrial fibrillation who undergo percutaneous
coronary intervention.
AB - INTRODUCTION: Balancing the risk of recurrent ischemia and bleeding among
patients with non-valvular atrial fibrillation who undergo percutaneous coronary
intervention (PCI) is challenging. Postprocedural antithrombotic therapy aims to
reduce the risk related to coronary artery disease, stent placement, and atrial
fibrillation, with acceptable risks of bleeding. Areas covered: This review
summarizes evidence and recommendations related to long-term antithrombotic
strategies in such patients. An overview of the findings from recent meta
analyses and select observational studies is provided, and important completed
and ongoing randomized trials are described in detail. Recommendations pertaining
to treatment intensity and duration, including the choice of specific
anticoagulant and antiplatelet agents, are given. Expert opinion: Triple therapy
(oral anticoagulation with dual antiplatelet therapy) is associated with an
increased bleeding risk compared with double therapy (oral anticoagulation with a
single antiplatelet agent), but double therapy does not appear to be associated
with an increased risk of recurrent ischemia or death. Completed trials make a
compelling case for double therapy with clopidogrel, not aspirin, when compared
with full-intensity triple antithrombotic therapy. We believe that double therapy
with an anticoagulant and clopidogrel should generally be favored instead of
triple antithrombotic therapy.
PMID- 28489476
TI - Benefits of Thoracic Epidural Analgesia in Patients Undergoing an Open Posterior
Component Separation for Abdominal Herniorrhaphy.
AB - An open posterior component separation (PCS) is a commonly utilized surgical
approach for repair of complex abdominal wall defects and hernias. Although this
approach may improve surgical outcomes, significant postoperative pain can be
expected given the required laparotomy and extensive abdominal wall manipulation.
Both systemic opioids and thoracic epidural analgesia (TEA) are viable
postoperative analgesic options, and both are commonly utilized. Although the
benefits of TEA have been investigated following a variety of surgeries, there is
a paucity of literature related to its efficacy for this particular surgery. The
aim of this study was to evaluate the benefits of TEA following open PCS under
the hypothesis that the incorporation of TEA into the postoperative analgesic
regimen would hasten bowel recovery. Patients who previously underwent an open
PCS were identified through an electronic medical record query. A retrospective
chart review was then performed, and patients who had TEA, either alone or
combined with systemic opioids, were compared with patients who had only systemic
opioids. The primary end point was a comparison of the postoperative day (POD) on
which a full diet was started. Secondarily, time to liquid diet, postsurgical
length of stay (LOS), intensive care unit (ICU) admission rate, ICU LOS, and the
rates of several postoperative adverse events were compared. A post hoc analysis
was also performed, using the same end points, to compare the subgroup of TEA
patients who avoided systemic opioids with all patients who received systemic
opioids, whether alone or combined with TEA. One hundred and one patients were
ultimately included for analysis. Time to full diet was not significantly
different between patients who had TEA, either with or without systemic opioids,
and those who received only systemic opioids (TEA 2.6 +/- 1.7 vs. systemic
opioids 3.1 +/- 2.1 [mean POD +/- SD], P = .21). Additionally, no statistically
significant differences were found for any secondary outcome. In the post hoc
analysis, the subgroup of TEA patients who avoided systemic opioids had a
significantly faster time to bowel recovery when compared with all patients who
received systemic opioids (2.2 +/- 1.0 vs. 3.2 +/- 2.2, P = .0033). This subgroup
also had a significantly shorter time to liquid diet and a decreased
postoperative LOS. In conclusion, for patients undergoing an open PCS, the
inclusion of TEA in the postoperative analgesic regimen did not by itself hasten
the return of bowel function. However, when TEA was utilized and systemic opioids
were avoided, bowel recovery occurred significantly sooner and resulted in a
shortened hospital LOS.
PMID- 28489477
TI - Combined Sciatic and Lumbar Plexus Nerve Blocks for the Analgesic Management of
Hip Arthroscopy Procedures: A Retrospective Review.
AB - Hip arthroscopy is a minimally invasive alternative to open hip surgery. Despite
its minimally invasive nature, there can still be significant reported pain
following these procedures. The impact of combined sciatic and lumbar plexus
nerve blocks on postoperative pain scores and opioid consumption in patients
undergoing hip arthroscopy was investigated. A retrospective analysis of 176
patients revealed that compared with patients with no preoperative peripheral
nerve block, significant reductions in pain scores to 24 hours were reported and
decreased opioid consumption during the post anesthesia care unit (PACU) stay was
recorded; no significant differences in opioid consumption out to 24 hours were
discovered. A subgroup analysis comparing two approaches to the sciatic nerve
block in patients receiving the additional lumbar plexus nerve block failed to
reveal a significant difference for this patient population. We conclude that
peripheral nerve blockade can be a useful analgesic modality for patients
undergoing hip arthroscopy.
PMID- 28489478
TI - Continuous Intravenous Lidocaine Infusion for the Management of Pain Uncontrolled
by Opioid Medications.
AB - Limited data exist describing the outcomes of patients receiving continuous
lidocaine infusions. The objective of this study was to evaluate the effect of
use of continuous lidocaine infusions for pain management at a community teaching
hospital. A retrospective chart review was performed that included adult patients
receiving continuous systemic lidocaine infusions for the treatment of pain.
Twenty-one patients were included in the analysis. Dosing ranged from 0.25 to 2.8
mg/kg/h, with a median infusion time of 64 hours. Eight patients (38%)
experienced a response (>=20% reduction in pain score during the infusion
compared with prior to the infusion). Among responding patients, there was a
decrease in pain scores at rest after starting lidocaine (compared with prior to
lidocaine) (6.5 vs. 3.7, P = .001) that was maintained 24 hours after lidocaine
discontinuation. There were no differences in pain scores before, during, or
after lidocaine in the entire study sample. A difference in oral morphine
equivalent intake was present comparing usage during the infusion vs. day +1 (P =
.006) and day +2 (P < .001). Similarly, a difference was present comparing
morphine equivalent usage on day -2 with day +2 (P = .008) and day -1 with day +1
(P = .006). Continuous infusions of systemic lidocaine appear to be beneficial in
some patients experiencing uncontrolled pain and may improve pain scores while
decreasing opioid requirements. Overall beneficial effects of systemic lidocaine
may last longer than the infusion itself.
PMID- 28489479
TI - Biologics and dermatology life quality index (DLQI) in the Australasian psoriasis
population.
AB - BACKGROUND/OBJECTIVES: Psoriasis is a chronic condition that may require long
term treatment for disease control. This analysis utilizes data from the
Australasian Psoriasis Registry with particular attention to the impact of
biologic therapy on DLQI, and the differences between the biologics in terms of
DLQI score change. METHODS: A retrospective review of patients enrolled in the
Australasian Psoriasis Registry from April 2008 to August 2016 was conducted. All
subjects from the registry that had DLQI and Psoriasis Assessment Severity Index
(PASI) scores recorded at a baseline time point of treatment commencement, in
addition to week 12 and 24 post commencement were included in the study. A window
of +/-3 weeks was permitted at these time points. Multivariate linear regression
analysis was undertaken to identify significant predictors associated with change
in DLQI. RESULTS: Significant predictors of reduction in DLQI and PASI score from
baseline to week 24 include use of adalimumab, infliximab, secukinumab and
ustekinumab. Other therapies, including etanercept and oral systemic agents did
not show significant change. Each class of biologic showed significant reductions
in DLQI score, with IL-12/23 blockade showing the greatest reduction. Significant
predictors of lack of reduction in DLQI score include a baseline PASI score <16,
and history of diabetes, alcoholism or uveitis. CONCLUSIONS: Patients with
moderate to severe chronic plaque psoriasis who are treated with biologics show
the greatest reduction in DLQI score, compared with other treatments. Australian
dermatologists are prescribing biologics when patients qualify for them in
keeping with current guidelines.
PMID- 28489480
TI - Ponesimod, a selective sphingosine 1-phosphate (S1P1) receptor modulator for
autoimmune diseases: review of clinical pharmacokinetics and drug disposition.
AB - 1. Ponesimod, a selective sphingosine 1-phosphate (S1P1) receptor modulator, is
undergoing clinical development for the treatment of autoimmune diseases
(multiple sclerosis/psoriasis). 2. Published literature data describing
pharmacokinetic disposition of ponesimod were collected, reviewed and tabulated.
3. Across various clinical phase-I studies, ponesimod displayed consistent
pharmacokinetics - relatively faster absorption peak time (approximately 2.5 h),
elimination half-life of approximately 30 h and modest accumulation (2- to 2.6
fold). Ponesimod was extensively metabolized and two major metabolites were ACT
204426 and ACT-338375. 4. Extensive population pharmacokinetic-pharmacodynamic
modeling has confirmed the therapeutic dose(s) for ponesimod to achieve the
balance between safety (primarily heart rate) and efficacy using the maximum
inhibition of the total lymphocytes as the pharmacodynamic marker. 5. None of the
covariates (ethnicity, body weight, sex, diseased state including multiple
sclerosis and psoriasis, food intake, formulation, etc.) examined in population
pharmacokinetic model influenced the pharmacokinetics of ponesimod from a
clinical relevance perspective. However, hepatic impairment (moderate/severe but
not mild), profoundly influenced its disposition; and therefore, would
necessitate dosage adjustment of ponesimod in clinical therapy. 6. Ponesimod has
a favorable safety profile and pharmacokinetics, which will allow maximizing its
ability to inhibit circulating lymphocytes in a given dosing regimen for treating
autoimmune diseases.
PMID- 28489481
TI - Efficient Trial Design - FDA Approval of Valbenazine for Tardive Dyskinesia.
PMID- 28489482
TI - Real world prescription trends of methotrexate for psoriasis in Argentina:
results of a national survey.
AB - OBJECTIVE: To describe dermatologists' methotrexate (MTX) prescription trends for
the treatment of psoriasis, and to identify variables associated with suboptimal
MTX use. METHODS: Cross-sectional study of dermatologists from Argentina who
completed a pre-designed survey focussed on MTX prescription characteristics. A
multiple logistic regression model was used to identify variables independently
associated with suboptimal MTX use (when less than 12 weeks and less than 15
mg/week were administrated in patients with monotherapy before discontinuing or
adding a second drug). RESULTS: Two hundred and twenty-one dermatologists
participated in the study. Median time of practice in dermatology: 10 (IQR 3-15)
years. MTX initial dose: 2.5-7.5, 10-15 and 20-30 mg/week in 52%, 41% and 7% of
the participants, respectively. Suboptimal MTX use was observed in 76% of the
participants. Thirty per cent of the participants responded that they considered
MTX to be an ineffective drug. The only variable that was independently
associated with suboptimal MTX use was the prescriber's personal consideration of
MTX to be an ineffective drug (OR 2.29; 95%CI 1.05-5.00). CONCLUSION: A wide
heterogeneity in the prescribing profile of MTX for the treatment of psoriasis
was observed among Argentinean dermatologists. Suboptimal MTX use was identified
in the majority of the prescribers.
PMID- 28489483
TI - A low initial botulinum toxin A treatment response does not predict poor long
term outcomes in patients with axillary bromhidrosis.
AB - PURPOSE: For patients with axillary bromhidrosis, it is not clear that whether a
low response to initial botulinum toxin A (BTX-A) treatment is related to poor
long-term outcomes. PATIENTS AND METHODS: From August 2011 to March 2016, 31
patients with primary axillary bromhidrosis were recruited. They had the duration
of efficacy for less than 4 weeks (median, 3 weeks; range, 1-3 weeks) after the
first BTX-A injection (50 U per underarm) and were considered to have a low
response to BTX-A treatment. The second injection with the same dose was
immediately administered once the symptoms recurred. Subsequent sessions were
performed with a double dose. RESULTS: The duration of efficacy rose
significantly to 10 weeks (range, 1-24 weeks) after the second injection (p <
.01). Twenty-five patients received the third injection. The resultant duration
further increased to 16 weeks (range, 12-26 weeks). No patients reported adverse
effects during our follow-up period. CONCLUSIONS: For patients with primary
axillary bromhidrosis, a low initial BTX-A treatment response does not predict
poor long-term outcomes. Immediate reinjection with the same dose and subsequent
sessions with a double dose is a safe strategy and can increase the duration of
BTX-A therapy.
PMID- 28489484
TI - Factors affecting the course and severity of adult acne. Observational cohort
study.
AB - OBJECTIVE: To identify factors improving symptoms and shortening duration of AA.
MATERIAL AND METHODS: The observational cohort study was performed in 111
patients with AA (>25 y.o.) in 2015-2016. Clinical manifestation, previous
treatments, environmental risk factors and features of juvenile acne affecting AA
were assessed. RESULTS: The maximum severity of persistent acne was significantly
lower after 25 years of age, as compared to adolescence (7.2 vs. 6.4; p = .0027).
The number of acne therapies used in AA was twice as high as in juvenile acne (22
vs. 11). The severity of AA sufficient to leave scars was significantly lower
than of juvenile acne (6.0 vs. 7.3; p = .0001) with 22% of patients developing
scars only in adult life. Patients linked exacerbations to stress exposure (p =
.09 and <.0001 for those reporting at least one stressor and all patients,
respectively), finding lifestyle changes the most stressful (p = .046). Those
using full-coverage foundations received significantly more acne treatments over
lifetime (5.4 vs. 3.6; p = .0359) and for AA (4.4 vs. 2.8; p = .0043).
Discontinuation of oral contraceptives or sensitive, erythema-prone skin also
worsened the symptoms. CONCLUSION: Lifestyle change-related stress, sensitive
skin, discontinuation of oral contraceptives and using full-coverage foundations
increase severity of AA.
PMID- 28489486
TI - Benzathine penicillin G once-every-3-week prophylaxis for recurrent erysipelas a
retrospective study of 132 patients.
AB - OBJECTIVE: To evaluate effectivity, safety and patients' adherence to benzathine
penicillin G (BPG) 1,200,000 units (1.2 MU) once-every-3-week intramuscularly
prophylaxis for recurrent erysipelas. METHODS: Patients with documented two or
more erysipelas episodes in last two years who received at least one of 10
planned doses of BPG 1.2 MU intramuscularly between January 2009 and December
2015 were analyzed in this retrospective study. Number of recurrences during the
30-week prophylaxis and in the 30-week follow-up period, frequency of adverse
events, patients' adherence to the treatment and factors associated with the
recurrence were analyzed. RESULTS: From 132 patients, 109 (82.6%) finished the 30
week prophylactic regimen successfully. The incidence of erysipelas was 8 per 100
patient-years during the prophylactic period and 28 per 100 patient-years in the
follow-up period (incidence rate ratio = 0.20; 95% CI: 0.05-0.34; p < .01). In
univariate analysis recurrence was significantly associated only with presence of
any local risk factor concurrently with obesity (OR 3.40; 95% CI: 1.10-10.50; p <
.05). CONCLUSION: Benzathine penicillin G 1.2 MU once every 3 weeks is an
effective and well-tolerated prophylaxis of recurrent erysipelas with good
patient adherence to the treatment. Further studies to determine the appropriate
duration of prophylaxis are necessary.
PMID- 28489485
TI - IGF-1 Mediates EphrinB1 Activation in Regulating Tertiary Dentin Formation.
AB - Eph receptors belong to a subfamily of receptor tyrosine kinases that are
activated by membrane-spanning ligands called ephrins. Previously, we
demonstrated that the ephrinB1-EphB2 interaction regulates odontogenic/osteogenic
differentiation from dental pulp cells (DPCs) in vitro. The goal of this study
was to identify the molecular mechanisms regulated by the EphB2/ephrinB1 system
that govern tertiary dentin formation in vitro and in vivo. During tooth
development, ephrinB1, and EphB2 were expressed in preodontoblast and
odontoblasts at postnatal day 4. EphrinB1 was continuously expressed in
odontoblasts and odontoblastic processes until the completion of tooth eruption.
In addition, ephrinB1 was expressed in odontoblastic processes 2 wk following
tooth injury without pulp exposure, whereas EphB2 was expressed in the center of
pulp niches but not odontoblasts. In a model of tooth injury with pulp exposure,
ephrinB1 was strongly expressed in odontoblasts 4 wk postinjury. In vitro studies
with human and mouse DPCs treated with calcium hydroxide (CH) or mineral trioxide
aggregate (MTA) showed an increased expression of insulin-like growth factor 1
(IGF-1). Experiments using several inhibitors of IGF-1 receptor signaling
revealed that inhibiting the Ras/Raf-1/MAPK pathway inhibited EphB2 expression,
and inhibiting the PI3K/Akt/mTOR pathway specifically inhibited ephrinB1 gene
expression. Tooth injury in mice with odontoblast-specific IGF-1 receptor
ablation exhibited a reduced tertiary dentin volume, mineral density, and
ephrinB1 expression 4 wk following injury. We conclude that the IGF-1/ephrinB1
axis plays significant roles in the early stages of tooth injury. Further
research is needed to fully understand the potential of targeting ephrinB1 as a
regenerative pulp therapy.
PMID- 28489487
TI - What did the March for Science stand for?
PMID- 28489489
TI - Trajectories of Community-Based Service Use: The Importance of Poverty and Living
Arrangements.
AB - This study examined how older adults' living arrangements and poverty status
affected their use of in-home health, functional, and out-of-home services over
time. Using eight waves of data from the Korea Welfare Panel Study, we employed a
logistic mixed-effect model to analyze how poverty and living arrangements affect
community-based service use. Living-alone older adults and elder-only couples
were more likely than co-residing households to use services. Elder-only couples,
when poor, were more likely to use in-home and out-of-home services over time.
Understanding predictors of community-based service use over time enables
researchers and policymakers to better understand the process of aging-in-place.
PMID- 28489491
TI - Risk Factors for Symptoms of Prescription Opioid Misuse: Do Older Adults Differ
from Younger Adult Patients?
AB - Limited research is available regarding the health risks associated with opioid
medication misuse among middle age (50-64 years) and older adults (65 and older).
Understanding the misuse symptom risk profiles of these populations has potential
to advance the national opioid epidemic response. A survey was conducted in four
community pharmacies in southwestern Pennsylvania among adult, non-cancer
patients filling opioid medications (N = 318) regarding opioid medication misuse
symptoms and misuse risk factors. Descriptive and multivariate statistical
analyses compared respondent characteristics, misuse symptoms, and misuse risks
among those 65 and older, 50 to 64, and those less than 50 years old. Those 65
and older (Incidence Rate Ratio [IRR] = 2.4, 95% CI = 1.46-3.95) and those 50 to
64 years (IRR = 1.26, 95% CI = 1.03-1.54) who reported illicit drug use had
increased rates of misuse symptoms. Those 50-64 with posttraumatic stress
disorder also had an increased rate of misuse symptoms (IRR = 1.29, 95% CI = 1.08
1.54). Misuse behaviors of those 65 and older and 50-64 involved shortening time
between dosages (>=65 = 11.4%, 50-64 = 27.6%), taking higher dosages than
prescribed (>=65 = 11.4%, 50-64 = 13.6%), and early refills (>=11.8%, 50-64 =
12.7%). Gerontological social workers must continue to work to understand and
identify individuals engaged in misuse in order to develop and provide age
appropriate care.
PMID- 28489488
TI - Radiation-Induced Fibrosis: Mechanisms and Opportunities to Mitigate. Report of
an NCI Workshop, September 19, 2016.
AB - A workshop entitled "Radiation-Induced Fibrosis: Mechanisms and Opportunities to
Mitigate" (held in Rockville, MD, September 19, 2016) was organized by the
Radiation Research Program and Radiation Oncology Branch of the Center for Cancer
Research (CCR) of the National Cancer Institute (NCI), to identify critical
research areas and directions that will advance the understanding of radiation
induced fibrosis (RIF) and accelerate the development of strategies to mitigate
or treat it. Experts in radiation biology, radiation oncology and related fields
met to identify and prioritize the key areas for future research and clinical
translation. The consensus was that several known and newly identified targets
can prevent or mitigate RIF in pre-clinical models. Further, basic and
translational research and focused clinical trials are needed to identify optimal
agents and strategies for therapeutic use. It was felt that optimally designed
preclinical models are needed to better study biomarkers that predict for
development of RIF, as well as to understand when effective therapies need to be
initiated in relationship to manifestation of injury. Integrating appropriate
endpoints and defining efficacy in clinical trials testing treatment of RIF were
felt to be critical to demonstrating efficacy. The objective of this meeting
report is to (a) highlight the significance of RIF in a global context, (b)
summarize recent advances in our understanding of mechanisms of RIF,
PMID- 28489492
TI - "The Action Level"(r).
PMID- 28489490
TI - The Role of Variability in Motor Learning.
AB - Trial-to-trial variability in the execution of movements and motor skills is
ubiquitous and widely considered to be the unwanted consequence of a noisy
nervous system. However, recent studies have suggested that motor variability may
also be a feature of how sensorimotor systems operate and learn. This view,
rooted in reinforcement learning theory, equates motor variability with
purposeful exploration of motor space that, when coupled with reinforcement, can
drive motor learning. Here we review studies that explore the relationship
between motor variability and motor learning in both humans and animal models. We
discuss neural circuit mechanisms that underlie the generation and regulation of
motor variability and consider the implications that this work has for our
understanding of motor learning.
PMID- 28489493
TI - Characterization of cellulolytic enzyme system of Schizophyllum commune mutant
and evaluation of its efficiency on biomass hydrolysis.
AB - Schizophyllum commune is a basidiomycete equipped with an efficient cellulolytic
enzyme system capable of growth on decaying woods. In this study, production of
lignocellulose-degrading enzymes from S. commune mutant G-135 (SC-Cel) on various
cellulosic substrates was examined. The highest cellulase activities including
CMCase, FPase, and beta-glucosidase were obtained on Avicel-PH101 while a wider
range of enzymes attacking non-cellulosic polysaccharides and lignin were found
when grown on alkaline-pretreated biomass. Proteomic analysis of SC-Cel also
revealed a complex enzyme system comprising seven glycosyl hydrolase families
with an accessory carbohydrate esterase, polysaccharide lyase, and auxiliary
redox enzymes. SC-Cel obtained on Avicel-PH101 effectively hydrolyzed all
agricultural residues with the maximum glucan conversion of 98.0% using corn cobs
with an enzyme dosage of 5 FPU/g-biomass. The work showed potential of SC-Cel on
hydrolysis of various herbaceous biomass with enhanced efficiency by addition
external beta-xylosidase.
PMID- 28489494
TI - Differences in meanings made according to prolonged grief symptomatology.
AB - This study investigated differences in specific meanings made following
bereavement, according to participants' prolonged grief symptomatology. A survey
of 580 bereaved adults (Mage = 61.6 years, 70.7% female) showed 13 meanings
predicted symptomatology, with the largest differences between the two lower
symptomatology groups and the high symptomatology group; the latter was more
likely to report no meaning. The results provide further support for empirically
distinct groups within the bereaved population, not only in terms of symptoms,
etiology, outcomes, courses, and treatment responses, but also in their meanings
made, and may assist in advancing meaning reconstruction interventions.
PMID- 28489495
TI - Research with Older Adult Methadone Clients: The Importance of Monitoring Suicide
Ideation.
AB - This study reports on the importance of monitoring suicide ideation among older
adult research participants. A recently completed randomized controlled trial of
older adults who are current clients in methadone maintenance treatment (MMT)
served as a case study to elucidate a suicide protocol that was designed to
account for the potential instances of suicide ideation within the research
project structure. As the numbers of older adult heroin users increases, this
study's findings seek to influence research protocols that involve older adults
with addictions who may be particularly vulnerable to suicide risk due to
comorbid psychiatric conditions and psychosocial adversities.
PMID- 28489496
TI - Intergroup Contact: Using Storytelling to Increase Awareness of Lesbian and Gay
Older Adults in Long-Term Care Settings.
AB - Due to societally imposed stigmatization, lesbian and gay (LG) older adults fear
and prolong accessing long-term care (LTC) even though they need LTC at higher
rates. Interventions that decrease negative attitudes toward LG older adults
among LTC staff are a first step in addressing this problem. In this study, the
influence of intergroup contact (IGC) on LTC staff members' attitudes toward LG
was explored through the use of storytelling as a training mechanism. An embedded
mixed-method approach was employed to collect and analyze responses of 60 LTC
staff who participated in a storytelling event. Participants completed pretests,
posttests, and participated in audio-recorded group discussions. The findings
showed that storytelling had a significant (p =0.001) and positive effect (d
=0.57) on participants attitudes toward LG. Qualitative analysis revealed 90
codes, 13 process codes, and 4 themes: making meaning of stories, seeking
understanding, application to LTC setting, and debating. When guided by IGC
theory, storytelling has potential for positively influencing attitudes of LTC
staff members toward LG older adults. There is a need for longitudinal work to
further test this model.
PMID- 28489497
TI - Ecology and Genomic Insights into Plant-Pathogenic and Plant-Nonpathogenic
Endophytes.
AB - Plants are colonized on their surfaces and in the rhizosphere and phyllosphere by
a multitude of different microorganisms and are inhabited internally by
endophytes. Most endophytes act as commensals without any known effect on their
plant host, but multiple bacteria and fungi establish a mutualistic relationship
with plants, and some act as pathogens. The outcome of these plant-microbe
interactions depends on biotic and abiotic environmental factors and on the
genotype of the host and the interacting microorganism. In addition, endophytic
microbiota and the manifold interactions between members, including pathogens,
have a profound influence on the function of the system plant and the development
of pathobiomes. In this review, we elaborate on the differences and similarities
between nonpathogenic and pathogenic endophytes in terms of host plant response,
colonization strategy, and genome content. We furthermore discuss environmental
effects and biotic interactions within plant microbiota that influence
pathogenesis and the pathobiome.
PMID- 28489498
TI - Fusarium oxysporum and the Fusarium Wilt Syndrome.
AB - The Fusarium oxysporum species complex (FOSC) comprises a multitude of strains
that cause vascular wilt diseases of economically important crops throughout the
world. Although sexual reproduction is unknown in the FOSC, horizontal gene
transfer may contribute to the observed diversity in pathogenic strains.
Development of disease in a susceptible crop requires F. oxysporum to advance
through a series of transitions, beginning with spore germination and culminating
with establishment of a systemic infection. In principle, each transition
presents an opportunity to influence the risk of disease. This includes
modifications of the microbial community in soil, which can affect the ability of
pathogen propagules to survive, germinate, and infect plant roots. In addition,
many host attributes, including the composition of root exudates, the structure
of the root cortex, and the capacity to recognize and respond quickly to invasive
growth of a pathogen, can impede development of F. oxysporum.
PMID- 28489499
TI - The Evidential Basis of Decision Making in Plant Disease Management.
AB - The evidential basis for disease management decision making is provided by data
relating to risk factors. The decision process involves an assessment of the
evidence leading to taking (or refraining from) action on the basis of a
prediction. The primary objective of the decision process is to identify-at the
time the decision is made-the control action that provides the best predicted end
of-season outcome, calculated in terms of revenue or another appropriate metric.
Data relating to disease risk factors may take a variety of forms (e.g.,
continuous, discrete, categorical) on measurement scales in a variety of units.
Log10-likelihood ratios provide a principled basis for the accumulation of
evidence based on such data and allow predictions to be made via Bayesian
updating of prior probabilities.
PMID- 28489500
TI - Does One Year of Schooling Improve Children's Cognitive Control and Alter
Associated Brain Activation?
AB - The "5-to-7-year shift" refers to the remarkable improvements observed in
children's cognitive abilities during this age range, particularly in their
ability to exert control over their attention and behavior-that is, their
executive functioning. As this shift coincides with school entry, the extent to
which it is driven by brain maturation or by exposure to formal schooling is
unclear. In this longitudinal study, we followed 5-year-olds born close to the
official cutoff date for entry into first grade and compared those who
subsequently entered first grade that year with those who remained in
kindergarten, which is more play oriented. The first graders made larger
improvements in accuracy on an executive-function test over the year than did the
kindergartners. In an independent functional MRI task, we found that the first
graders, compared with the kindergartners, exhibited a greater increase in
activation of right posterior parietal cortex, a region previously implicated in
sustained attention; increased activation in this region was correlated with the
improvement in accuracy. These results reveal how the environmental context of
formal schooling shapes brain mechanisms underlying improved focus on cognitively
demanding tasks.
PMID- 28489501
TI - Smoking Cessation Treatment for Patients With Mental Disorders Using CBT and
Combined Pharmacotherapy.
AB - OBJECTIVES: The aim of this study was to investigate smoking treatment
effectiveness and retention in a population with and without mental disorders
(MD). Participants received cognitive behavioral therapy (CBT) plus nicotine
patch alone or in combination with other medications (i.e., gum, bupropion, or
nortriptyline) for smoking cessation treatment in a Brazilian Psychosocial Care
Center unit (CAPS), taking into account sociodemographics and smoking profile
covariates. METHODS: The study involved comparison of treatment success (seven
day point prevalence abstinence at the end of the treatment) and retention
(presence of the individual in all of the four medical consultations and six
group sessions) in two subsamples of patients with MD (n = 267) and without MD (n
= 397) who were included in a six-week treatment provided by a CAPS from 2007 to
2013. The treatment protocol comprised group CBT and pharmacotherapy (nicotine
patches, nicotine gums, and bupropion and nortriptyline available, prescribed by
psychiatrists). RESULTS: Within patients with MD, CBT plus nicotine patch plus
bupropion (aOR = 2.00, 95% CI [1.14, 3.50], p = .015) and CBT plus nicotine patch
plus gum (aOR = 2.10, 95% CI [1.04, 4.23], p = .036) were associated with
treatment success. Within patients without MD, female gender (aOR = 0.60, 95% CI
[0.37, 0.95], p = .031) and lower Heaviness of Smoking Index score (aOR = 0.80,
95% CI [0.65, 0.99], p = .048) were associated with treatment success. No
variable was associated with dropout or retention within patients with or without
MD. CONCLUSION: Our findings support the use of CBT plus nicotine patch plus
bupropion as well as CBT plus nicotine patch plus gum in samples with high rates
of medical, psychiatric, and addiction disorders. These findings support those of
previous studies in the general population. Pharmacological treatment associated
with group CBT based on cognitive-behavioral concepts and combined with ongoing
MD treatment seems to be the best option for smoking cessation treatment among
patients with MD. Units that deal with patients with MD, such as CAPS in Brazil,
should be encouraged to treat smoking addiction in this population. Future
studies should investigate retention rates in other samples of patients with MD.
PMID- 28489502
TI - Advances in cardiac pacing and defibrillation.
AB - INTRODUCTION: There have been many evolutionary milestones in cardiac implantable
electronic device (CIED) therapy over the past few decades. These advancements
have created new challenges. Right ventricular pacing was the original (late
1950s) breakthrough, however the risk of pacing induced dyssynchrony has become
evident. Biventricular pacing provided a viable way to mitigate dyssynchrony, but
only benefits certain patients (primarily left bundle branch block and QRS
duration >=150 ms with depressed left ventricular (LV) function). Areas covered:
Recent advances have made His Bundle pacing an option that may provide
physiological pacing for a wider patient population. Traditional CIED systems
utilize transvenous endocardial leads. Unfortunately, leads have been CIEDs'
weakest link. Lead-related vascular occlusion, infection and malfunction have
spurred the need for percutaneous lead extraction, and development of
subcutaneous ICDs and leadless pacing. These options are important for
individuals with limited vascular access and those at risk for blood borne
infection. Subcutaneous ICDs have been proposed as optimal for younger patients.
This recommendation is controversial. Expert commentary: We review recent
advances including His bundle pacing, percutaneous lead extraction, leadless
pacing and subcutaneous ICDs as well as their potential use in combination.
Additional technological evolution promises to make the future of CIEDs exciting.
PMID- 28489503
TI - Does Prehospital Time Influence Clinical Outcomes in Severe Trauma Patients?: A
Cross Sectional Study.
AB - OBJECTIVE: Prehospital time potentially impacts clinical outcomes in severely
injured trauma patients. The importance of individual components, including scene
and response time, however, is controversial. Our objective was to determine the
impact of prehospital times on survival in severely injured patients. METHODS: We
reviewed injured trauma patients enrolled in a Korean EMS trauma registry during
2012. Severe trauma patients were defined as having either a "V" or lower in the
AVPU system, a systolic blood pressure <=90mmHg, or respiratory rate <10 or >29.
Patients with Injury Severity Scores(ISS) < 9 were excluded. Patients were
categorized by scene time into 4 groups as follows: <3 minutes, 3-6 minutes, 6-9
minutes, and >=9 minutes and by prehospital time as follows: <16 minutes, 16-24
minutes, 24-32 minutes, and >=32 minutes. The primary outcome was in-hospital
mortality. Multiple linear regression analysis was used to adjust for possible
confounders. RESULTS: A total of 2,257 eligible patients were analyzed. Scene
time was <3 minutes in 220 (9.7%), 3-6 in 865 (38.3%), 6-9 in 587 (26.0%), and
>=9 in 585 (25.9%). In-hospital mortality was 396 (17.5%). Compared to a scene
time 6 to 9 minutes, mortality was higher as the scene time decreased: odds ratio
(OR) = 1.3(3 to <6), OR = 1.9(0 to <3). Mortality was slightly decreased as
prehospital time increased, OR = 1.0(16 to <24), OR = 0.9(24 to <32), OR =
0.7(>=32). CONCLUSION: Longer prehospital times did not increase mortality in
severely injured trauma patients in Korea. Furthermore, longer scene times were
associated with lower mortality.
PMID- 28489504
TI - Validation of the cell line LS180 as a model for study of the gastrointestinal
toxicity of mycophenolic acid.
AB - 1. Gastrointestinal (GI) intolerability is a concern for drugs such as
mycophenolic acid (MPA) and drug metabolism may play a role. Few in vitro models
exist that allow for the preclinical evaluation of a potential role of drug
metabolism in intestinal drug toxicity. Thus, we sought to develop an in vitro
model based on the human colon adenocarcinoma cell line LS180 to investigate
MPA's negative effects on intestinal cells. 2. Stability of expression of key
enzymes of MPA metabolism (UGT1A7, UGT1A9, UGT1A10, UGT2B7, CYP3A4 and CYP3A5),
transporters (OATP1B1, OATP1B3, OATP2B1, MRP1, MRP2 and MDR1) and the nuclear
receptor PXR over 12 passages in combination with guanosine supplementation to
counter MPA's antiproliferative effects (determined by western blot analysis and
proliferation assays, respectively) was established. 3. Expression of LS180 key
enzymes remained stable over passages 47-59 and MPA-induced growth inhibition was
circumvented by exogenous guanosine over a period of three days. MPA was not
cytotoxic at concentrations up to 250 MUM, a concentration that intestinal cells
adjacent to the dissolving capsule or tablet are exposed to. 4. We concluded that
LS180 cells are suitable to study the potential association between MPA
metabolism and its negative effects on intestinal cells.
PMID- 28489505
TI - Editorial.
PMID- 28489506
TI - Prehospital Intubation is Associated with Favorable Outcomes and Lower Mortality
in ProTECT III.
AB - OBJECTIVE: Traumatic brain injury (TBI) causes more than 2.5 million emergency
department visits, hospitalizations, or deaths annually. Prehospital endotracheal
intubation has been associated with poor outcomes in patients with TBI in several
retrospective observational studies. We evaluated the relationship between
prehospital intubation, functional outcomes, and mortality using high quality
data on clinical practice collected prospectively during a randomized multicenter
clinical trial. METHODS: ProTECT III was a multicenter randomized, double-blind,
placebo-controlled trial of early administration of progesterone in 882 patients
with acute moderate to severe nonpenetrating TBI. Patients were excluded if they
had an index GCS of 3 and nonreactive pupils, those with withdrawal of life
support on arrival, and if they had documented prolonged hypotension and/or
hypoxia. Prehospital intubation was performed as per local clinical protocol in
each participating EMS system. Models for favorable outcome and mortality
included prehospital intubation, method of transport, index GCS, age, race, and
ethnicity as independent variables. Significance was set at alpha = 0.05.
Favorable outcome was defined by a stratified dichotomy of the GOS-E scores in
which the definition of favorable outcome depended on the severity of the initial
injury. RESULTS: Favorable outcome was more frequent in the 349 subjects with
prehospital intubation (57.3%) than in the other 533 patients (46.0%, p = 0.003).
Mortality was also lower in the prehospital intubation group (13.8% v. 19.5%, p =
0.03). Logistic regression analysis of prehospital intubation and mortality,
adjusted for index GCS, showed that odds of dying for those with prehospital
intubation were 47% lower than for those that were not intubated (OR = 0.53, 95%
CI = 0.36-0.78). 279 patients with prehospital intubation were transported by
air. Modeling transport method and mortality, adjusted for index GCS, showed
increased odds of dying in those transported by ground compared to those
transported by air (OR = 2.10, 95% CI = 1.40-3.15). Decreased odds of dying
trended among those with prehospital intubation adjusted for transport method,
index GCS score at randomization, age, and race/ethnicity (OR = 0.70, 95% CI =
0.37-1.31). CONCLUSIONS: In this study that excluded moribund patients,
prehospital intubation was performed primarily in patients transported by air.
Prehospital intubation and air medical transport together were associated with
favorable outcomes and lower mortality. Prehospital intubation was not associated
with increased morbidity or mortality regardless of transport method or severity
of injury.
PMID- 28489507
TI - Development and Validation of the PREMM5 Model for Comprehensive Risk Assessment
of Lynch Syndrome.
AB - Purpose Current Lynch syndrome (LS) prediction models quantify the risk to an
individual of carrying a pathogenic germline mutation in three mismatch repair
(MMR) genes: MLH1, MSH2, and MSH6. We developed a new prediction model, PREMM5,
that incorporates the genes PMS2 and EPCAM to provide comprehensive LS risk
assessment. Patients and Methods PREMM5 was developed to predict the likelihood
of a mutation in any of the LS genes by using polytomous logistic regression
analysis of clinical and germline data from 18,734 individuals who were tested
for all five genes. Predictors of mutation status included sex, age at genetic
testing, and proband and family cancer histories. Discrimination was evaluated by
the area under the receiver operating characteristic curve (AUC), and clinical
impact was determined by decision curve analysis; comparisons were made to the
existing PREMM1,2,6 model. External validation of PREMM5 was performed in a
clinic-based cohort of 1,058 patients with colorectal cancer. Results Pathogenic
mutations were detected in 1,000 (5%) of 18,734 patients in the development
cohort; mutations included MLH1 (n = 306), MSH2 (n = 354), MSH6 (n = 177), PMS2
(n = 141), and EPCAM (n = 22). PREMM5 distinguished carriers from noncarriers
with an AUC of 0.81 (95% CI, 0.79 to 0.82), and performance was similar in the
validation cohort (AUC, 0.83; 95% CI, 0.75 to 0.92). Prediction was more
difficult for PMS2 mutations (AUC, 0.64; 95% CI, 0.60 to 0.68) than for other
genes. Performance characteristics of PREMM5 exceeded those of PREMM1,2,6.
Decision curve analysis supported germline LS testing for PREMM5 scores >= 2.5%.
Conclusion PREMM5 provides comprehensive risk estimation of all five LS genes and
supports LS genetic testing for individuals with scores >= 2.5%. At this
threshold, PREMM5 provides performance that is superior to the existing
PREMM1,2,6 model in the identification of carriers of LS, including those with
weaker phenotypes and individuals unaffected by cancer.
PMID- 28489508
TI - Tai Chi Chih Compared With Cognitive Behavioral Therapy for the Treatment of
Insomnia in Survivors of Breast Cancer: A Randomized, Partially Blinded,
Noninferiority Trial.
AB - Purpose Cognitive behavioral therapy for insomnia (CBT-I) and Tai Chi Chih (TCC),
a movement meditation, improve insomnia symptoms. Here, we evaluated whether TCC
is noninferior to CBT-I for the treatment of insomnia in survivors of breast
cancer. Patients and Methods This was a randomized, partially blinded,
noninferiority trial that involved survivors of breast cancer with insomnia who
were recruited from the Los Angeles community from April 2008 to July 2012. After
a 2-month phase-in period with repeated baseline assessment, participants were
randomly assigned to 3 months of CBT-I or TCC and evaluated at months 2, 3 (post
treatment), 6, and 15 (follow-up). Primary outcome was insomnia treatment
response-that is, marked clinical improvement of symptoms by the Pittsburgh Sleep
Quality Index-at 15 months. Secondary outcomes were clinician-assessed remission
of insomnia; sleep quality; total sleep time, sleep onset latency, sleep
efficiency, and awake after sleep onset, derived from sleep diaries;
polysomnography; and symptoms of fatigue, sleepiness, and depression. Results Of
145 participants who were screened, 90 were randomly assigned (CBT-I: n = 45;
TCC: n = 45). The proportion of participants who showed insomnia treatment
response at 15 months was 43.7% and 46.7% in CBT-I and TCC, respectively. Tests
of noninferiority showed that TCC was noninferior to CBT-I at 15 months ( P =
.02) and at months 3 ( P = .02) and 6 ( P < .01). For secondary outcomes,
insomnia remission was 46.2% and 37.9% in CBT-I and TCC, respectively. CBT-I and
TCC groups showed robust improvements in sleep quality, sleep diary measures, and
related symptoms (all P < .01), but not polysomnography, with similar
improvements in both groups. Conclusion CBT-I and TCC produce clinically
meaningful improvements in insomnia. TCC, a mindful movement meditation, was
found to be statistically noninferior to CBT-I, the gold standard for behavioral
treatment of insomnia.
PMID- 28489509
TI - AKT Inhibition in Solid Tumors With AKT1 Mutations.
AB - Purpose AKT1 E17K mutations are oncogenic and occur in many cancers at a low
prevalence. We performed a multihistology basket study of AZD5363, an ATP
competitive pan-AKT kinase inhibitor, to determine the preliminary activity of
AKT inhibition in AKT-mutant cancers. Patients and Methods Fifty-eight patients
with advanced solid tumors were treated. The primary end point was safety;
secondary end points were progression-free survival (PFS) and response according
to Response Evaluation Criteria in Solid Tumors (RECIST). Tumor biopsies and
plasma cell-free DNA (cfDNA) were collected in the majority of patients to
identify predictive biomarkers of response. Results In patients with AKT1 E17K
mutant tumors (n = 52) and a median of five lines of prior therapy, the median
PFS was 5.5 months (95% CI, 2.9 to 6.9 months), 6.6 months (95% CI, 1.5 to 8.3
months), and 4.2 months (95% CI, 2.1 to 12.8 months) in patients with estrogen
receptor-positive breast, gynecologic, and other solid tumors, respectively. In
an exploratory biomarker analysis, imbalance of the AKT1 E17K-mutant allele, most
frequently caused by copy-neutral loss-of-heterozygosity targeting the wild-type
allele, was associated with longer PFS (hazard ratio [HR], 0.41; P = .04), as was
the presence of coincident PI3K pathway hotspot mutations (HR, 0.21; P = .045).
Persistent declines in AKT1 E17K in cfDNA were associated with improved PFS (HR,
0.18; P = .004) and response ( P = .025). Responses were not restricted to
patients with detectable AKT1 E17K in pretreatment cfDNA. The most common grade
>= 3 adverse events were hyperglycemia (24%), diarrhea (17%), and rash (15.5%).
Conclusion This study provides the first clinical data that AKT1 E17K is a
therapeutic target in human cancer. The genomic context of the AKT1 E17K mutation
further conditioned response to AZD5363.
PMID- 28489510
TI - Safety and Antitumor Activity of Pembrolizumab in Advanced Programmed Death
Ligand 1-Positive Endometrial Cancer: Results From the KEYNOTE-028 Study.
AB - Purpose The multicohort phase Ib KEYNOTE-028 (NCT02054806) study was designed to
evaluate the safety and efficacy of pembrolizumab, an anti-programmed death 1
monoclonal antibody, in patients with programmed death ligand 1 (PD-L1) -positive
advanced solid tumors. The results from the advanced endometrial cancer cohort
are reported. Patients and Methods Female patients with locally advanced or
metastatic PD-L1-positive endometrial cancer who had experienced progression
after standard therapy were eligible. Patients received pembrolizumab 10 mg/kg
every 2 weeks for up to 24 months or until progression or unacceptable toxicity.
Primary efficacy end point was objective response rate by RECIST (version 1.1).
Secondary end points included safety, duration of response (DOR), progression
free survival, and overall survival. The data cutoff was February 17, 2016.
Results Of 75 patients screened, 36 (48.0%) had PD-L1-positive tumors, and 24
(32.0%) were enrolled. Fifteen (62.5%) of these 24 patients had received at least
two previous lines of therapy for advanced disease. Three patients (13.0%)
achieved confirmed partial response (95% CI, 2.8% to 33.6%); the median DOR was
not reached. Two patients were still receiving treatment and exhibiting continued
response at time of data cutoff. Three additional patients (13.0%) achieved
stable disease, with a median duration of 24.6 weeks. One patient who achieved
partial response had a polymerase E mutation. Thirteen patients (54.2%)
experienced treatment-related adverse events (AEs), with fatigue (20.8%),
pruritus (16.7%), pyrexia (12.5%), and decreased appetite (12.5%) occurring in >=
10% of patients. Grade 3 treatment-related AEs were reported in four patients. No
patient experienced a grade 4 AE, and no patient discontinued treatment because
of an AE. Conclusion Pembrolizumab demonstrated a favorable safety profile and
durable antitumor activity in a subgroup of patients with heavily pretreated
advanced PD-L1-positive endometrial cancer.
PMID- 28489512
TI - Ethnoracial differences in cannabis use among native-born and foreign-born high
school students in Ontario.
AB - The objective of this study was to examine the association of ethnoracial
background and immigrant status to cannabis use among students in Ontario,
Canada. Data were derived from the Ontario Student Drug Use and Health Survey, a
school-based, province-wide survey of students in Grades 7-12. The survey
utilized a stratified two-stage cluster design. Analyses were based on a pooled
subsample of 12,527 students in Grades 9-12 during the 2011 and 2013 survey
cycles and included adjustments for the complex sample design. Results indicate
that youth who were of South Asian or East/Southeast Asian background were at
lower odds of cannabis use than those who were White, Black, or mixed-race
backgrounds. Youth who were of mixed-race background (i.e., White and another
group) were at higher odds of cannabis use than youth who were of White
background. The association between ethnoracial background and cannabis use also
varied for some foreign-born and native-born youth. These findings suggest that
ethnoracial background should be an important consideration in investigations of
cannabis use among foreign- relative to native-born youth.
PMID- 28489511
TI - Phase III Randomized, Placebo-Controlled, Double-Blind Trial of Celecoxib in
Addition to Standard Chemotherapy for Advanced Non-Small-Cell Lung Cancer With
Cyclooxygenase-2 Overexpression: CALGB 30801 (Alliance).
AB - Purpose Tumor overexpression of cyclooxygenase-2 (COX-2) has been associated with
worse outcome in non-small-cell lung cancer (NSCLC). In Cancer and Leukemia Group
B (CALGB) 30203, we found that the selective COX-2 inhibitor celecoxib in
addition to chemotherapy in advanced NSCLC improved progression-free and overall
survival in patients with moderate to high COX-2 expression by
immunohistochemistry (IHC). CALGB 30801 (Alliance) was designed to prospectively
confirm that finding. Patients and Methods Patients with NSCLC (stage IIIB with
pleural effusion or stage IV according to American Joint Committee on Cancer
[sixth edition] criteria) were preregistered, and biopsy specimens were analyzed
for COX-2 by IHC. Patients with COX-2 expression >= 2, performance status of 0 to
2, and normal organ function were eligible. Chemotherapy was determined by
histology: carboplatin plus pemetrexed for nonsquamous NSCLC and carboplatin plus
gemcitabine for squamous histology. Patients were randomly assigned to celecoxib
(400 mg twice per day; arm A) or placebo (arm B). The primary objective was to
demonstrate improvement in progression-free survival in patients with COX-2 index
>= 4 with hazard ratio of 0.645 with approximately 85% power at two-sided
significance level of .05. Results The study was halted for futility after 312 of
the planned 322 patients with COX-2 index >= 2 were randomly assigned. There were
no significant differences between the groups (hazard ratio, 1.046 for COX-2 >=
4). Subset analyses evaluating histology, chemotherapy regimen, and incremental
COX-2 expression did not demonstrate any advantage for COX-2 inhibition.
Elevation of baseline urinary metabolite of prostaglandin E2, indicating
activation of the COX-2 pathway, was a negative prognostic factor. Values above
the third quartile may have been a predictive factor. Conclusion COX-2 expression
by IHC failed to select patients who could benefit from selective COX-2
inhibition. Urinary metabolite of prostaglandin E2 may be able to identify
patients who could benefit from COX-2 inhibition.
PMID- 28489514
TI - Expectations, gender, and norms in migration decision-making.
AB - This paper argues that expectations - the process of evaluating the chances for
future attainment of valued goals in the home community (stay decision) vs.
alternative locations (move decision) - along with family norms about migration
are major predictors of intention to move, which in turn is a proximate
determinant of migration behaviour. Utilizing longitudinal data from the 1992 and
1994 waves of the Thailand National Migration Survey, logistic regression models
show that a strikingly different set of expectations, household demographic
indicators, and migrant capital factors were significant determinants of
migration intentions for men and women; reflecting Thai gender roles. Migration
intentions, in turn, predicted more permanent, but not temporary, survival
strategy migration behaviour, while low household income predicted temporary but
not more permanent migration behaviour. The measure of perceived family migration
norms was a powerful determinant of migration behaviour, but the size of migrant
networks was not a statistically significant determinant of either migration
intentions or behaviour.
PMID- 28489513
TI - Thyroid Function during Early Life and Dental Development.
AB - Children with low levels of thyroid hormones (hypothyroidism) have delayed tooth
eruption, enamel hypoplasia, micrognathia, and anterior open bite, whereas
children with hyperthyroidism may suffer from accelerated tooth eruption,
maxillary, and mandibular osteoporosis. However, it is still unknown whether
thyroid function variations within the normal or subclinical range also have an
impact on hard dental tissues in healthy children. The objective of this study
was, therefore, to investigate the association between thyroid function from the
fetal period until early childhood and dental development at school age. This
study is embedded in the Generation R Study, a population-based cohort study
established in Rotterdam, the Netherlands. Maternal thyroid function (thyroid
stimulating hormone [TSH], free thyroxine [FT4], and thyroid peroxidase antibody
[TPOAb] concentrations) was measured during early pregnancy, and thyroid function
of the offspring (TSH and FT4) was measured in cord blood at birth and in early
childhood (6 y). Dental development was assessed from panoramic radiographs of
children of school-going age (9 y). In total, 2,387 to 2,706 subjects were
available for the multivariable linear regression analysis, depending on the
point in time of thyroid function measurement. There was an inverse association
between cord blood and early childhood TSH concentrations with dental
development, with a -0.06 lower standard deviation (SD) per 1 mU/L of TSH (95%
confidence interval [CI], -0.11 to -0.01) and a -0.06 lower SD per 1 mU/L of TSH
(95% CI, -0.11 to 0.00), respectively. There was no association between the
maternal thyroid function during pregnancy and the dental development score of
the child. However, TPOAb-positive mothers had children with a -0.20 SD (adjusted
95% CI, -0.35 to -0.04) lower dental development score compared with TPOAb
negative mothers. The findings of this study suggest that the thyroid hormone is
involved in the maturation of teeth from the early stages of life onward.
PMID- 28489516
TI - A reply to J. Antonio Ortega Osona and H-P Kohler.
PMID- 28489517
TI - Forgone income and motherhood: What do recent British data tell u?
AB - Children affect women s opportunities in the labour markets of most advanced
countries in three ways: an immediate effect on employment, and effects on longer
term earning power and pension coverage. This paper quantifies these impacts on
women s lifetime income for hypothetical illustrative British cases. New results,
based on data collected during the 1990s, are compared with estimates from 1980.
Although childrearing and employment have increasingly been combined over the
period, the estimated loss of gross earnings associated with motherhood remains
substantial. It still amounts to around half potential earnings post childbirth
for less qualified sections of the British female labour force, but has become
smaller for highly qualified women. The paper examines the effect of the
tax/benefit system on the costs, and makes some assumptions about the
distribution of net costs between mothers and fathers. It also shows how far
motherhood jeopardizes financial security in old age, particularly for the least
qualified.
PMID- 28489518
TI - A comment on "Recent European fertility patterns: Fitting curves to distorted
distributions" by T. Chandola, D. A. Coleman and R. W. Hiorns.
PMID- 28489519
TI - Validity and reliability of the Disabilities of Arm, Shoulder, and Hand scale in
dental students: A transnational study.
AB - This study aimed to evaluate the validity and reliability of the Disabilities of
Arm, Shoulder, and Hand (DASH) scale in Brazilian and American dental students
and assess the influence of demographic variables on disability in them. A cross
sectional observational study was conducted with a nonprobabilistic sample. The
sample was composed of students of both genders from the School of Dentistry of
Araraquara, State University of Sao Paulo (UNESP) (n = 288), and students from
Stony Brook University, New York, NY, USA (n = 149). The disabilities of the
upper limbs were estimated using the DASH scale. The samples were characterized
by collecting information on gender, academic year, and sports and work
activities. The refined bifactorial model presented goodness-of-fit indices for
both countries. There was a significant effect of the variables gender and
academic year for the Brazilian sample and the variable sports practices for the
American sample. The refined bifactorial model was valid and reliable for the
Brazilian and American populations. In this model, the removal of item 17 for the
Brazilian sample and items 3, 13, and 23 for the American sample was necessary.
Demographic variables such as gender, academic year, and sports practice
contributed significantly to the level of disability in the study populations.
PMID- 28489520
TI - Intergenerational exchanges in Vietnam: Family size, sex composition, and the
location of children.
PMID- 28489521
TI - Social inequalities in cancer survival.
AB - Social differentials in survival from twelve common types of cancer were assessed
by estimating a mixed additive-multiplicative hazard model on the basis of
individual register and census data for the whole Norwegian population. The
excess all-cause mortality among cancer patients compared with similar persons
without a cancer diagnosis was significantly related to education, occupation,
and income. Excess mortality was, on the whole, about 15 per cent lower for men
or women who had completed a post-secondary education than for those with only
compulsory schooling, taking into account age, period and registered differences
in tumour characteristics and stage at the time of diagnosis. The data do not
provide clear indications of whether differences in host factors, such as co
morbidities and immune functions, or differences in treatment and care are
primarily responsible for these inequalities in cancer survival.
PMID- 28489523
TI - Dynamics of marriage change in Chinese rural society in transition: A study of a
northern Chinese village.
AB - This analysis uses data from an intensive village study to investigate the
impacts of institutional reforms on marriage in rural China. The study finds that
age at marriage has been declining significantly both for men and women. The
'exchange marriage' and the 'mercenary marriage' have re-emerged. An increasing
proportion of marriages occur between men and women in nearby villages, though
there is no significant increase in village endogamy. Both bride price and dowry
have increased significantly, and the ratio of value of dowry to bride price has
undergone a dramatic equalization. The young, including young women, have much
more decision making power regarding their marriages. Changes in marriage are the
consequences of both change in the socio-economic environment brought about by
deliberate rural reforms, and strategic or tactical responses of rural Chinese to
the rapidly changing context in which they live and work.
PMID- 28489524
TI - Gender in population research: Confusing implications for health policy.
AB - In this paper I discuss some of the health policy implications of an increasing
trend in population research and in its interpretation and presentation - a trend
to 'political correctness' - defined not in the popular, often derogatory, sense,
but as an ideological commitment to certain principles. For one of these
commitments, that to the notion of gender equality, greater strength and
legitimacy is today commonly sought by tying it to other less controversial goals
such as that of better health. But straining for connections between gender
equality and positive health outcomes often unduly constrains the research
question, the research methods, and the interpretation of the research. When
health policy seeks guidance from this research, it can receive signals which are
too often incomplete, silent on the many trade-offs of specific policy measures,
and, ultimately, perhaps even detrimental to the very goals of gender equity and
social justice from which they are derived. Examples of all these possibilities
are discussed.
PMID- 28489525
TI - The evolution of cohabitation in Britain, 1960-95.
AB - The recent rise in cohabitation in Britain is analysed using data from large
scale surveys. There are major inconsistencies between different sources, and
retrospective estimates are higher than values reported at the time.
Retrospective data show markedly smaller numbers of cohabitation events just
before survey date. I discuss reasons for discrepancies and conclude that no
objective measure of cohabitation exists and that comparison of different types
of data requires care. I combine the data to produce a much larger data set than
hitherto available. Although cohabitation prevalence increased substantially
during the 1970s and 1980s, there was little change in such characteristics as
duration of cohabitation, ages of those cohabiting, and whether it occurred
before first marriage or ended in marriage or breakdown. However, since the late
1980s, the average length of cohabitation has increased markedly, which may
indicate a qualitative change in the nature of cohabitation in Britain.
PMID- 28489526
TI - Trends in cohabitation and implications for children s family contexts in the
United States.
AB - This paper documents increasing cohabitation in the United States, and the
implications of this trend for the family lives of children. The stability of
marriage-like relationships (including marriage and cohabitation) has decreased
despite a constant divorce rate. Children increasingly live in cohabiting
families either as a result of being born to cohabiting parents or of their
mother s entry into a cohabiting union. The proportion of births to unmarried
women born into cohabiting families increased from 29 to 39 per cent in the
period 1980-84 to 1990-94, accounting for almost all of the increase in unmarried
childbearing. As a consequence, about two-fifths of all children spend some time
in a cohabiting family, and the greater instability of families begun by
cohabitation means that children are also more likely to experience family
disruption. Estimates from multi-state life tables indicate the extent to which
the family lives of children are spent increasingly in cohabiting families and
decreasingly in married families.
PMID- 28489527
TI - Role of Glucomannans in Immunology.
AB - Glucomannans play a much broader role in human health then providing dietary
fibre. They are biologically active molecules and can when added to the body
imitate innate molecules found in different organs including surface
carbohydrates on cells. This review considers the immunological role of exogenous
glucomannans within animals and man. This article is open to POST-PUBLICATION
REVIEW. Registered readers (see "For Readers") may comment by clicking on
ABSTRACT on the issue's contents page.
PMID- 28489529
TI - Modeling Touch and Palpation Using Autoregressive Models.
AB - OBJECTIVE: The human haptic system uses a set of reproducible and subconscious
hand maneuvers to identify objects. Similar subconscious maneuvers are used
during medical palpation for screening and diagnosis. The goal of this work was
to develop a mathematical model that can be used to describe medical palpation
techniques. METHODS: Palpation data were measured using a two-dimensional array
of force sensors. A novel algorithm for estimating the hand position from force
data was developed. The hand position data were then modeled using multivariate
autoregressive models. Analysis of these models provided palpation direction and
frequency as well as palpation type. The models were tested and validated using
three different data sets: simulated data, a simplified experiment in which
participant followed a known pattern, and breast simulator palpation data.
RESULTS: Simulated data showed that the minimal error in estimating palpation
direction and frequency is achieved when the sampling frequency is five to ten
times the palpation frequency. The classification accuracy was for the simplified
experiment and for the breast simulator data. CONCLUSION: Proper palpation is one
of the vital components of many hands-on clinical examinations. In this study, an
algorithm for characterizing medical palpation was developed. The algorithm
measured palpation frequency and direction for the first time and provided
classification of palpation type. SIGNIFICANCE: These newly developed models can
be used for quantifying and assessing clinical technique, and consequently, lead
to improved performance in palpation-based exams. Furthermore, they provide a
general tool for the study of human haptics.
PMID- 28489528
TI - Reciprocal synapses between mushroom body and dopamine neurons form a positive
feedback loop required for learning.
AB - Current thought envisions dopamine neurons conveying the reinforcing effect of
the unconditioned stimulus during associative learning to the axons of Drosophila
mushroom body Kenyon cells for normal olfactory learning. Here, we show using
functional GFP reconstitution experiments that Kenyon cells and dopamine neurons
from axoaxonic reciprocal synapses. The dopamine neurons receive cholinergic
input via nicotinic acetylcholine receptors from the Kenyon cells; knocking down
these receptors impairs olfactory learning revealing the importance of these
receptors at the synapse. Blocking the synaptic output of Kenyon cells during
olfactory conditioning reduces presynaptic calcium transients in dopamine
neurons, a finding consistent with reciprocal communication. Moreover, silencing
Kenyon cells decreases the normal chronic activity of the dopamine neurons. Our
results reveal a new and critical role for positive feedback onto dopamine
neurons through reciprocal connections with Kenyon cells for normal olfactory
learning.
PMID- 28489530
TI - Real-Time Three-Dimensional Microwave Monitoring of Interstitial Thermal Therapy.
AB - We report a method for real-time three-dimensional monitoring of thermal therapy
through the use of noncontact microwave imaging. This method is predicated on
using microwaves to image changes in the dielectric properties of tissue with
changing temperature. Instead of the precomputed linear Born approximation that
was used in prior work to speed up the frame-to-frame inversions, here we use the
nonlinear distorted Born iterative method (DBIM) to solve the electric volume
integral equation (VIE) to image the temperature change. This is made possible by
using a recently developed graphic processing unit accelerated conformal finite
difference time domain method to solve the forward problem and update the
electric field in the monitored region in each DBIM iteration. Compared to our
previous work, this approach provides a far superior approximation of the
electric field within the VIE, and thus yields a more accurate reconstruction of
tissue temperature change. The proposed method is validated using a realistic
numerical model of interstitial thermal therapy for a deep-seated brain lesion.
With the new DBIM, we reduced the average estimation error of the mean
temperature within the region of interest from 2.5 to 1.0 for the noise-free
case, and from 2.9 to 1.7 for the 2% background noise case.
PMID- 28489531
TI - 3D Object Localisation from Multi-View Image Detections.
AB - In this work we present a novel approach to recover objects 3D position and
occupancy in a generic scene using only 2D object detections from multiple view
images. The method reformulates the problem as the estimation of a quadric
(ellipsoid) in 3D given a set of 2D ellipses fitted to the object detection
bounding boxes in multiple views. We show that a closed-form solution exists in
the dual-space using a minimum of three views while a solution with two views is
possible through the use of non-linear optimisation and object constraints on the
size of the object shape. In order to make the solution robust toward inaccurate
bounding boxes, a likely occurrence in object detection methods, we introduce a
data preconditioning technique and a non-linear refinement of the closed form
solution based on implicit subspace constraints. Results on synthetic tests and
on different real datasets, involving challenging scenarios, demonstrate the
applicability and potential of our method in several realistic scenarios.
PMID- 28489532
TI - Video Super-Resolution via Bidirectional Recurrent Convolutional Networks.
AB - Super resolving a low-resolution video, namely video super-resolution (SR), is
usually handled by either single-image SR or multi-frame SR. Single-Image SR
deals with each video frame independently, and ignores intrinsic temporal
dependency of video frames which actually plays a very important role in video
SR. Multi-Frame SR generally extracts motion information, e.g., optical flow, to
model the temporal dependency, but often shows high computational cost.
Considering that recurrent neural networks (RNNs) can model long-term temporal
dependency of video sequences well, we propose a fully convolutional RNN named
bidirectional recurrent convolutional network for efficient multi-frame SR.
Different from vanilla RNNs, 1) the commonly-used full feedforward and recurrent
connections are replaced with weight-sharing convolutional connections. So they
can greatly reduce the large number of network parameters and well model the
temporal dependency in a finer level, i.e., patch-based rather than frame-based,
and 2) connections from input layers at previous timesteps to the current hidden
layer are added by 3D feedforward convolutions, which aim to capture discriminate
spatio-temporal patterns for short-term fast-varying motions in local adjacent
frames. Due to the cheap convolutional operations, our model has a low
computational complexity and runs orders of magnitude faster than other multi
frame SR methods. With the powerful temporal dependency modeling, our model can
super resolve videos with complex motions and achieve well performance.
PMID- 28489533
TI - Shakeout: A New Approach to Regularized Deep Neural Network Training.
AB - Recent years have witnessed the success of deep neural networks in dealing with a
plenty of practical problems. Dropout has played an essential role in many
successful deep neural networks, by inducing regularization in the model
training. In this paper, we present a new regularized training approach:
Shakeout. Instead of randomly discarding units as Dropout does at the training
stage, Shakeout randomly chooses to enhance or reverse each unit's contribution
to the next layer. This minor modification of Dropout has the statistical trait:
the regularizer induced by Shakeout adaptively combines , and regularization
terms. Our classification experiments with representative deep architectures on
image datasets MNIST, CIFAR-10 and ImageNet show that Shakeout deals with over
fitting effectively and outperforms Dropout. We empirically demonstrate that
Shakeout leads to sparser weights under both unsupervised and supervised
settings. Shakeout also leads to the grouping effect of the input units in a
layer. Considering the weights in reflecting the importance of connections,
Shakeout is superior to Dropout, which is valuable for the deep model
compression. Moreover, we demonstrate that Shakeout can effectively reduce the
instability of the training process of the deep architecture.
PMID- 28489534
TI - Dynamic 2-D/3-D Rigid Registration Framework Using Point-To-Plane Correspondence
Model.
AB - In image-guided interventional procedures, live 2-D X-ray images can be augmented
with preoperative 3-D computed tomography or MRI images to provide planning
landmarks and enhanced spatial perception. An accurate alignment between the 3-D
and 2-D images is a prerequisite for fusion applications. This paper presents a
dynamic rigid 2-D/3-D registration framework, which measures the local 3-D-to-2-D
misalignment and efficiently constrains the update of both planar and non-planar
3-D rigid transformations using a novel point-to-plane correspondence model. In
the simulation evaluation, the proposed method achieved a mean 3-D accuracy of
0.07 mm for the head phantom and 0.05 mm for the thorax phantom using single-view
X-ray images. In the evaluation on dynamic motion compensation, our method
significantly increases the accuracy comparing with the baseline method. The
proposed method is also evaluated on a publicly-available clinical angiogram data
set with "gold-standard" registrations. The proposed method achieved a mean 3-D
accuracy below 0.8 mm and a mean 2-D accuracy below 0.3 mm using single-view X
ray images. It outperformed the state-of-the-art methods in both accuracy and
robustness in single-view registration. The proposed method is intuitive,
generic, and suitable for both initial and dynamic registration scenarios.
PMID- 28489535
TI - Lead-Free Multilayer Piezoceramic Composites: Effect of Cosintering on
Electromechanical Properties.
AB - The macroscopic electromechanical behavior of lead-free multilayer composites was
characterized from room temperature to 150 degrees C. The polar seed component
consisted of a nonergodic relaxor (Bi1/2Na1/2)TiO3-7BaTiO3, with an electric
field-induced long-range ferroelectric order, whereas the nonpolar matrix was an
ergodic relaxor Bi0.5(Na0.75K0.25)0.5 TiO3-6BiAlO3 that undergoes a reversible
electric-field-induced macroscopic nonpolar-to-polar transition. Microstructural
evidence of the effects of cosintering are demonstrated through examination of
grain size, interdiffusion, and pore structure. By manipulating the sintering
interactions between the two constituents, namely, diffusion paths and residual
stresses, both internal mechanical and electrical fields, as well as
compositional gradients can be used to enhance the unipolar strain over that
expected by a rule of mixtures approximation, thereby improving the properties
needed for application of such materials to actuator systems.
PMID- 28489537
TI - Real-Time Video Stylization Using Object Flows.
AB - We present a real-time video stylization system and demonstrate a variety of
painterly styles rendered on real video inputs. The key technical contribution
lies on the object flow, which is robust to inaccurate optical flow, unknown
object transformation and partial occlusion as well. Since object flows relate
regions of the same object across frames, shower-door effect can be effectively
reduced where painterly strokes and textures are rendered on video objects. The
construction of object flows is performed in real time and automatically after
applying metric learning. To reduce temporal flickering, we extend the bilateral
filtering into motion bilateral filtering. We propose quantitative metrics to
measure the temporal coherence on structures and textures of our stylized videos,
and perform extensive experiments to compare our stylized results with baseline
systems and prior works specializing in watercolor and abstraction.
PMID- 28489538
TI - A Perception-Driven Approach to Supervised Dimensionality Reduction for
Visualization.
AB - Dimensionality reduction (DR) is a common strategy for visual analysis of labeled
high-dimensional data. Low-dimensional representations of the data help, for
instance, to explore the class separability and the spatial distribution of the
data. Widely-used unsupervised DR methods like PCA do not aim to maximize the
class separation, while supervised DR methods like LDA often assume certain
spatial distributions and do not take perceptual capabilities of humans into
account. These issues make them ineffective for complicated class structures.
Towards filling this gap, we present a perception-driven linear dimensionality
reduction approach that maximizes the perceived class separation in projections.
Our approach builds on recent developments in perception-based separation
measures that have achieved good results in imitating human perception. We extend
these measures to be density-aware and incorporate them into a customized
simulated annealing algorithm, which can rapidly generate a near optimal DR
projection. We demonstrate the effectiveness of our approach by comparing it to
state-of-the-art DR methods on 93 datasets, using both quantitative measure and
human judgments. We also provide case studies with class-imbalanced and unlabeled
data.
PMID- 28489536
TI - Dual-Frequency Piezoelectric Endoscopic Transducer for Imaging Vascular Invasion
in Pancreatic Cancer.
AB - Cancers of the pancreas have the poorest prognosis among all cancers, as many
tumors are not detected until surgery is no longer a viable option. Surgical
viability is typically determined via endoscopic ultrasound imaging. However,
many patients who may be eligible for resection are not offered surgery due to
diagnostic challenges in determining vascular or lymphatic invasion. In this
paper, we describe the development of a dual-frequency piezoelectric transducer
for rotational endoscopic imaging designed to transmit at 4 MHz and receive at 20
MHz in order to image microbubble-specific superharmonic signals. Imaging
performance is assessed in a tissue-mimicking phantom at depths from 1 cm
[contrast-to-tissue ratio (CTR) = 21.6 dB] to 2.5 cm (CTR = 11.4 dB), in ex vivo
porcine vessels, and in vivo in a rodent. The prototyped 1.1-mm aperture
transducer demonstrates contrast-specific imaging of microbubbles in a 200-
[Formula: see text]-diameter tube through the wall of a 1-cm-diameter porcine
artery, suggesting such a device may enable direct visualization of small vessels
from within the lumen of larger vessels such as the portal vein or superior
mesenteric vein.
PMID- 28489539
TI - Task-Independent Mental Workload Classification Based Upon Common Multiband EEG
Cortical Connectivity.
AB - Efficient classification of mental workload, an important issue in neuroscience,
is limited, so far to single task, while cross-task classification remains a
challenge. Furthermore, network approaches have emerged as a promising direction
for studying the complex organization of the brain, enabling easier
interpretation of various mental states. In this paper, using two mental tasks (N
back and mental arithmetic), we present a framework for cross- as well as within
task workload discrimination by utilizing multiband electroencephalography (EEG)
cortical brain connectivity. In detail, we constructed functional networks in EEG
source space in different frequency bands and considering the individual
functional connections as classification features, we identified salient feature
subsets based on a sequential feature selection algorithm. These connectivity
subsets were able to provide accuracy of 87% for cross-task, 88% for N-back task,
and 86% for mental arithmetic task. In conclusion, our method achieved to detect
a small number of discriminative interactions among brain areas, leading to high
accuracy in both within-task and cross-task classifications. In addition, the
identified functional connectivity features, the majority of which were detected
in frontal areas in theta and beta frequency bands, helped delineate the shared
as well as the distinct neural mechanisms of the two mental tasks.
PMID- 28489540
TI - Nonlinear Frequency-Domain Analysis of the Transformation of Cortical Inputs by a
Motoneuron Pool-Muscle Complex.
AB - Corticomotor coherence in the beta and/or gamma bands has been described in
different motor tasks, but the role of descending brain oscillations on force
control has been elusive. Large-scale computational models of a motoneuron pool
and the muscle it innervates have been used as tools to advance the knowledge of
how neural elements may influence force control. Here, we present a frequency
domain analysis of a NARX model fitted to a large-scale neuromuscular model by
the means of generalized frequency response functions (GFRF). The results of such
procedures indicated that the computational neuromuscular model was capable of
transforming an oscillatory synaptic input (e.g., at 20 Hz) into a constant mean
muscle force output. The nonlinearity uncovered by the GFRFs of the NARX model
was responsible for the demodulation of an oscillatory input (e.g., a beta band
oscillation coming from the brain and forming the input to the motoneuron pool).
This suggests a manner by which brain rhythms descending as command signals to
the spinal cord and acting on a motoneuron pool can regulate a maintained muscle
force. In addition to the scientific aspects of these results, they provide new
interpretations that may further neural engineering applications associated with
quantitative neurological diagnoses and robotic systems for artificial limbs.
PMID- 28489542
TI - A Grouping Particle Swarm Optimizer with Personal-Best-Position Guidance for
Large Scale Optimization.
AB - Particle Swarm Optimization (PSO) is a popular algorithm which is widely
investigated and well implemented in many areas. However, the canonical PSO does
not perform well in population diversity maintenance so that usually leads to a
premature convergence or local optima. To address this issue, we propose a
variant of PSO named Grouping PSO with Personal- Best-Position (Pbest) Guidance
(GPSO-PG) which maintains the population diversity by preserving the diversity of
exemplars. On one hand, we adopt uniform random allocation strategy to assign
particles into different groups and in each group the losers will learn from the
winner. On the other hand, we employ personal historical best position of each
particle in social learning rather than the current global best particle. In this
way, the exemplars diversity increases and the effect from the global best
particle is eliminated. We test the proposed algorithm to the benchmarks in CEC
2008 and CEC 2010, which concern the large scale optimization problems (LSOPs).
By comparing several current peer algorithms, GPSO-PG exhibits a competitive
performance to maintain population diversity and obtains a satisfactory
performance to the problems.
PMID- 28489543
TI - Integrating Multiple Heterogeneous Networks for Novel LncRNA-disease Association
Inference.
AB - Accumulating experimental evidence has indicated that long non-coding RNAs
(lncRNAs) are critical for the regulation of cellular biological processes
implicated in many human diseases. However, only relatively few experimentally
supported lncRNA-disease associations have been reported. Developing effective
computational methods to infer lncRNA-disease associations is becoming
increasingly important. Current network-based algorithms typically use a network
representation to identify novel associations between lncRNAs and diseases. But
these methods are concentrated on specific entities of interest (lncRNAs and
diseases) and they do not allow to consider networks with more than two types of
entities. Considering the limitations in previous computational methods, we
develop a new global network-based framework, LncRDNetFlow, to prioritize disease
related lncRNAs. LncRDNetFlow utilizes a flow propagation algorithm to integrate
multiple networks based on a variety of biological information including lncRNA
similarity, protein-protein interactions, disease similarity and the associations
between them to infer lncRNA-disease associations. We show that LncRDNetFlow
performs significantly better than the existing stat-ofthe- art approaches in
cross-validation. To further validate the reproducibility of the performance, we
use the proposed method to identify the related lncRNAs for ovarian cancer,
glioma and cervical cancer. The results are encouraging. Many predicted lncRNAs
in the top list have been verified by the biological studies.
PMID- 28489541
TI - The Effect of Prosthesis Use on Hand Mental Rotation After Unilateral Upper-Limb
Amputation.
AB - Amputation of a limb induces changes in the so-called body schema, which might be
influenced by the use of prosthetic devices. Changes in the body representation
associated with prosthesis use could be investigated using a hand mental rotation
task. However, direct neurophysiologic evidence for the effect of prosthesis use
on hand mental rotation is still lacking. In this paper, we recruited two groups
of unilateral upper-limb amputees, i.e., amputees using a prosthesis or with a
history of prosthesis use (Pro group) and amputees without a prosthesis (non-Pro
group), as well as a sample of matched healthy controls. Using concurrent
behavioral and electrophysiological assessments, we found that Pro amputees were
comparable to healthy controls in either behavior or event-related potentials
(ERPs), while non-Pro amputees showed prolonged response time as well as
divergent ERP patterns. The P200 amplitude of non-Pro amputees was significantly
larger for the non-dominant hand pictures than that for the dominant hand
pictures, while such a hand difference in P200 was not found in either healthy
controls or Pro amputees. Furthermore, the typical angular modulation of the N200
amplitude in healthy controls and Pro amputees was not presented in non-Pro
amputees. Our results suggest that prosthesis use could preserve mental rotation
ability by maintaining the performance of motor imagery and visual perception of
hands, which represents a preservation of the body schema.
PMID- 28489544
TI - An Improved Approach for N-linked Glycan Structure Identification from HCD MS/MS
Spectra.
AB - Glycosylation is a frequently observed posttranslational modification on
proteins. Currently, tandem mass spectrometry (MS/MS) serves as an efficient
analytical technique for characterizing structures of oligosaccharides. However,
developing effective computational approaches for identifying glycan structures
from mass spectra is still a great challenge in glycoproteomics research. In this
study, we proposed an approach for matching the input spectra with glycan
structures acquired from a glycan structure database by incorporating a de novo
sequencing assisted ranking scheme. The proposed approach is implemented as a
software tool, GlycoNovoDB, for automated glycan structure identification from
HCD MS/MS of glycopeptides. Experimental results showed that GlycoNovoDB can
identify glycans effectively and has better performance than our previously
proposed de novo sequencing algorithm as well as another software GlycoMaster DB.
PMID- 28489545
TI - Learning a structural and functional representation for gene expressions: To
systematically dissect complex cancer phenotypes.
AB - Cancer is a heterogeneous disease, thus one of the central problems is how to
dissect the resulting complex phenotypes in terms of their biological building
blocks. Computationally, this is to represent and interpret high dimensional
observations through a structural and conceptual abstraction into the most
influential determinants underlying the problem. The working hypothesis of this
report is to consider gene interaction to be largely responsible for the
manifestation of complex cancer phenotypes, thus where the representation is to
be conceptualized. Here we report a representation learning strategy combined
with regularizations, in which gene expressions are described in terms of a
regularized product of meta-genes and their expression levels. The meta-genes are
constrained by gene interactions thus representing their original topological
contexts. The expression levels are supervised by their conditional dependencies
among the observations thus providing a cluster-specific constraint. We obtain
both of these structural constraints using a node-based graphical model. Our
representation allows the selection of more influential modules, thus implicating
their possible roles in neoplastic transformations. We validate our
representation strategy by its robust recognitions of various cancer phenotypes
comparing with various classical methods. The modules discovered are either
shared or specify for different types or stages of human cancers, all of which
are consistent with literature and biology.
PMID- 28489546
TI - A Novel AMARS Technique for Baseline Wander Removal Applied to
Photoplethysmogram.
AB - A new digital filter, AMARS (aligning minima of alternating random signal) has
been derived using trigonometry to regulate signal pulsations inline. The pulses
are randomly presented in continuous signals comprising frequency band lower than
the signal's mean rate. Frequency selective filters are conventionally employed
to reject frequencies undesired by specific applications. However, these
conventional filters only reduce the effects of the rejected range producing a
signal superimposed by some baseline wander (BW). In this work, filters of
different ranges and techniques were independently configured to preprocess a
photoplethysmogram, an optical biosignal of blood volume dynamics, producing wave
shapes with several BWs. The AMARS application effectively removed the
encountered BWs to assemble similarly aligned trends. The removal implementation
was found repeatable in both ear and finger photoplethysmograms, emphasizing the
importance of BW removal in biosignal processing in retaining its structural,
functional and physiological properties. We also believe that AMARS may be
relevant to other biological and continuous signals modulated by similar types of
baseline volatility.
PMID- 28489547
TI - A 172 $?mu$W Compressively Sampled Photoplethysmographic (PPG) Readout ASIC With
Heart Rate Estimation Directly From Compressively Sampled Data.
AB - A compressive sampling (CS) photoplethysmographic (PPG) readout with embedded
feature extraction to estimate heart rate (HR) directly from compressively
sampled data is presented. It integrates a low-power analog front end together
with a digital back end to perform feature extraction to estimate the average HR
over a 4 s interval directly from compressively sampled PPG data. The application
specified integrated circuit (ASIC) supports uniform sampling mode (1x
compression) as well as CS modes with compression ratios of 8x, 10x, and 30x. CS
is performed through nonuniformly subsampling the PPG signal, while feature
extraction is performed using least square spectral fitting through Lomb-Scargle
periodogram. The ASIC consumes 172 MU W of power from a 1.2 V supply while
reducing the relative LED driver power consumption by up to 30 times without
significant loss of relevant information for accurate HR estimation.
PMID- 28489548
TI - Retinal Circuit Emulator With Spatiotemporal Spike Outputs at Millisecond
Resolution in Response to Visual Events.
AB - To gain insights on how visual information of the real world is filtered,
compressed, and encoded by the vertebrate retinas, emulating in silico the
spatiotemporal patterns of the graded and action potentials of neuronal responses
to natural visual scenes on biological time scale is a feasible approach. As a
basic platform for such an emulation, we here developed a compact hardware system
comprising an analog silicon retina and a field-programmable gate array module.
With utilizing the Izhikevich formalism, a retinal circuit model that emulates
spiking of ganglion cells was implemented in this system. The emulated spike
timing had the resolution of about 2 ms relative to the stimulus onset and was
little affected by timings of the synchronous frame sampling in the silicon
retina. Thus, the emulator can mimic the event-driven spike outputs of biological
retinas. The system was useful for simultaneously visualizing neural images of
both the graded potentials and the spikes in response to real live visual scenes.
Since our emulator system is reconfigurable, it provides a flexible platform for
investigating visual functions of retinal circuits under natural visual
environment.
PMID- 28489549
TI - Secure and Energy-Efficient Data Transmission System Based on Chaotic Compressive
Sensing in Body-to-Body Networks.
AB - Applications of wireless body area networks (WBANs) are extended from remote
health care to military, sports, disaster relief, etc. With the network scale
expanding, nodes increasing, and links complicated, a WBAN evolves to a body-to
body network. Along with the development, energy saving and data security
problems are highlighted. In this paper, chaotic compressive sensing (CCS) is
proposed to solve these two crucial problems, simultaneously. Compared with the
traditional compressive sensing, CCS can save vast storage space by only storing
the matrix generation parameters. Additionally, the sensitivity of chaos can
improve the security of data transmission. Aimed at image transmission, modified
CCS is proposed, which uses two encryption mechanisms, confusion and mask, and
performs a much better encryption quality. Simulation is conducted to verify the
feasibility and effectiveness of the proposed methods. The results show that the
energy efficiency and security are strongly improved, while the storage space is
saved. And the secret key is extremely sensitive, [Formula: see text]
perturbation of the secret key could lead to a total different decoding, the
relative error is larger than 100%. Particularly for image encryption, the
performance of the modified method is excellent. The adjacent pixel correlation
is smaller than 0.04 in different directions including horizontal, vertical, and
diagonal; the entropy of the cipher image with a 256-level gray value is larger
than 7.98.
PMID- 28489551
TI - On the Dynamics of Hopfield Neural Networks on Unit Quaternions.
AB - In this paper, we first address the dynamics of the elegant multivalued
quaternionic Hopfield neural network (MV-QHNN) proposed by Minemoto et al.
Contrary to what was expected, we show that the MV-QHNN, as well as one of its
variation, does not always come to rest at an equilibrium state under the usual
conditions. In fact, we provide simple examples in which the network yields a
periodic sequence of quaternionic state vectors. Afterward, we turn our attention
to the continuous-valued quaternionic Hopfield neural network (CV-QHNN), which
can be derived from the MV-QHNN by means of a limit process. The CV-QHNN can be
implemented more easily than the MV-QHNN model. Furthermore, the asynchronous CV
QHNN always settles down into an equilibrium state under the usual conditions.
Theoretical issues are all illustrated by examples in this paper.
PMID- 28489550
TI - A Fully Integrated Wireless SoC for Motor Function Recovery After Spinal Cord
Injury.
AB - This paper presents a wirelessly powered, fully integrated system-on-a-chip (SoC)
supporting 160-channel stimulation, 16-channel recording, and 48-channel bio
impedance characterization to enable partial motor function recovery through
epidural spinal cord electrical stimulation. A wireless transceiver is designed
to support quasi full-duplex data telemetry at a data rate of 2 Mb/s.
Furthermore, a unique in situ bio-impedance characterization scheme based on time
domain analysis is implemented to derive the Randles cell electrode model of the
electrode-electrolyte interface. The SoC supports concurrent stimulation and
recording while the high-density stimulator array meets an output compliance
voltage of up to +/-10 V with versatile stimulus programmability. The SoC
consumes 18 mW and occupies a chip area of 5.7 mm * 4.4 mm using 0.18 MUm high
voltage CMOS process. In our in vivo rodent experiment, the SoC is used to
perform wireless recording of EMG responses while stimulation is applied to
enable the standing and stepping of a paralyzed rat. To facilitate the system
integration, a novel thin film polymer packaging technique is developed to
provide a heterogeneous integration of the SoC, coils, discrete components, and
high-density flexible electrode array, resulting in a miniaturized prototype
implant with a weight and form factor of 0.7 g and 0.5 cm3, respectively.
PMID- 28489552
TI - Structure Learning for Deep Neural Networks Based on Multiobjective Optimization.
AB - This paper focuses on the connecting structure of deep neural networks and
proposes a layerwise structure learning method based on multiobjective
optimization. A model with better generalization can be obtained by reducing the
connecting parameters in deep networks. The aim is to find the optimal structure
with high representation ability and better generalization for each layer. Then,
the visible data are modeled with respect to structure based on the products of
experts. In order to mitigate the difficulty of estimating the denominator in
PoE, the denominator is simplified and taken as another objective, i.e., the
connecting sparsity. Moreover, for the consideration of the contradictory nature
between the representation ability and the network connecting sparsity, the
multiobjective model is established. An improved multiobjective evolutionary
algorithm is used to solve this model. Two tricks are designed to decrease the
computational cost according to the properties of input data. The experiments on
single-layer level, hierarchical level, and application level demonstrate the
effectiveness of the proposed algorithm, and the learned structures can improve
the performance of deep neural networks.
PMID- 28489553
TI - Data-Driven Learning Control for Stochastic Nonlinear Systems: Multiple
Communication Constraints and Limited Storage.
AB - This paper proposes a data-driven learning control method for stochastic
nonlinear systems under random communication conditions, including data dropouts,
communication delays, and packet transmission disordering. A renewal mechanism is
added to the buffer to regulate the arrived packets, and a recognition mechanism
is introduced to the controller for the selection of suitable update packets.
Both intermittent and successive update schemes are proposed based on the
conventional P-type iterative learning control algorithm, and are shown to
converge to the desired input with probability one. The convergence and
effectiveness of the proposed algorithms are verified by means of illustrative
simulations.
PMID- 28489554
TI - Reversed Spectral Hashing.
AB - Hashing is emerging as a powerful tool for building highly efficient indices in
large-scale search systems. In this paper, we study spectral hashing (SH), which
is a classical method of unsupervised hashing. In general, SH solves for the hash
codes by minimizing an objective function that tries to preserve the similarity
structure of the data given. Although computationally simple, very often SH
performs unsatisfactorily and lags distinctly behind the state-of-the-art
methods. We observe that the inferior performance of SH is mainly due to its
imperfect formulation; that is, the optimization of the minimization problem in
SH actually cannot ensure that the similarity structure of the high-dimensional
data is really preserved in the low-dimensional hash code space. In this paper,
we, therefore, introduce reversed SH (ReSH), which is SH with its input and
output interchanged. Unlike SH, which estimates the similarity structure from the
given high-dimensional data, our ReSH defines the similarities between data
points according to the unknown low-dimensional hash codes. Equipped with such a
reversal mechanism, ReSH can seamlessly overcome the drawback of SH. More
precisely, the minimization problem in our ReSH can be optimized if and only if
similar data points are mapped to adjacent hash codes, and mostly important,
dissimilar data points are considerably separated from each other in the code
space. Finally, we solve the minimization problem in ReSH by multilayer neural
networks and obtain state-of-the-art retrieval results on three benchmark data
sets.
PMID- 28489555
TI - Distributed Adaptive Containment Control for a Class of Nonlinear Multiagent
Systems With Input Quantization.
AB - This paper is devoted to distributed adaptive containment control for a class of
nonlinear multiagent systems with input quantization. By employing a matrix
factorization and a novel matrix normalization technique, some assumptions
involving control gain matrices in existing results are relaxed. By fusing the
techniques of sliding mode control and backstepping control, a two-step design
method is proposed to construct controllers and, with the aid of neural networks,
all system nonlinearities are allowed to be unknown. Moreover, a linear time
varying model and a similarity transformation are introduced to circumvent the
obstacle brought by quantization, and the controllers need no information about
the quantizer parameters. The proposed scheme is able to ensure the boundedness
of all closed-loop signals and steer the containment errors into an arbitrarily
small residual set. The simulation results illustrate the effectiveness of the
scheme.
PMID- 28489556
TI - Modeling the Length of Stay of Respiratory Patients in Emergency Department Using
Coxian Phase-Type Distributions With Covariates.
AB - Variability and unpredictability are typical features of emergency departments
(EDs) where patients randomly arrive with diverse conditions. Patient length of
stay (LOS) represents the consumption level of hospital resources, and it is
positively skewed and heterogeneous. Both accurate modeling of patient ED LOS and
analysis of potential blocking causes are especially useful for patient
scheduling and resource management. To tackle the uncertainty of ED LOS, this
paper introduces two methods: statistical modeling and distribution fitting. The
models are applied to 894 respiratory diseases patients data in the year 2014
from ED of a Chinese public tertiary hospital. Covariates recorded include
patient region, gender, age, arrival time, arrival mode, triage category, and
treatment area. A Coxian phase-type (PH) distribution model with covariates is
proposed as an alternative method for modeling ED LOS. The expectation
maximization (EM) algorithm is used to implement parameter estimation. The
results show that ED LOS data can be modeled well by the proposed models.
Distributions of ED LOS differ significantly with respect to patients' gender,
arrival mode, and treatment area. Using the fitted Coxian PH model will assist ED
managers in identifying patients who are most likely to have an extreme ED LOS
and in predicting the forthcoming workload for resources.
PMID- 28489557
TI - Reduced bone mineral density in Chinese children with phenylketonuria.
AB - BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive metabolic disorder.
Dietary control of classic PKU needs restriction of natural proteins. The diet
results in unbalanced nutrition, which might affect the physical development of
the patients. Our aim was to evaluate bone mineral density (BMD) in children with
PKU. METHODS: To investigate the BMD of children with PKU, 41 children with PKU
and 64 healthy controls were recruited (all 3-4 years of age). Body weight and
height, BMD, Phe blood levels, thyroid function, calcium, phosphorus, iron
metabolism markers, and vitamin D3 were measured. RESULTS: Body height and BMD of
patients were lower than in controls. The BMD of controls was positively
associated with age, body weight and height. In patients, BMD was positively
associated with body weight. There was no correlation between Phe blood levels
and BMD in patients. Blood levels of alkaline phosphatase were higher in patients
compared to controls. Blood calcium levels were higher in 4-year-old patients,
while the body weight was lower compared to controls. Thyroid function, iron
metabolism markers, vitamin D3 levels and IGF-1 levels were normal. CONCLUSIONS:
Reduced BMD was observed in children with phenylketonuria, but the exact reasons
for this remain to be elucidated.
PMID- 28489558
TI - Evaluation of factors associated with elevated newborn 17-hydroxyprogesterone
levels.
AB - BACKGROUND: Measurement of 17-hydroxyprogesterone (17-OHP) in dried blood spots
has been widely used as a newborn screening tool for congenital adrenal
hyperplasia (CAH). Various maternal and neonatal factors can result in falsely
high values of 17-OHP. There is a paucity of Indian studies in this regard
because routine evaluation of newborn 17-OHP levels as a screening program is not
widely practiced in India. Hence, this study was undertaken to evaluate the
influence of various maternal and neonatal factors on newborn 17-OHP levels. The
aim of the study was to determine the effect of various maternal and neonatal
factors on the newborn 17-OHP values. METHODS: Retrospective data related to a
total of 3080 newborn 17-OHP values and clinical characteristics were collected
for 3 years (2013-2015). The data were analyzed to determine the influence of
various factors on 17-OHP values. RESULTS: The mean value of 17-OHP in our study
was 5.486+/-3.96 ng/mL. Gender and mode of delivery did not significantly affect
the 17-OHP levels. The levels were significantly higher in preterm and low birth
weight babies as compared to term babies and babies with normal birth weight.
Stress factors like pregnancy induced hypertension (PIH), early onset sepsis
(EOS), neonatal seizures and birth asphyxia significantly increase the neonatal
17-OHP levels. CONCLUSIONS: The levels of 17-OHP in newborns was measured around
day 3 of life are very sensitive to the influence of gestational age, birth
weight and presence of stress factors like maternal PIH, birth asphyxia, neonatal
sepsis and neonatal seizures and should be interpreted cautiously.
PMID- 28489560
TI - Peripartum cardiomyopathy - from pathogenesis to treatment.
PMID- 28489559
TI - Neck circumference is similarly predicting for impairment of glucose tolerance as
classic anthropometric parameters among healthy and obese children and
adolescents.
AB - BACKGROUND: The objective of the study was to investigate the association of neck
circumference (NC) to parameters of glucose homeostasis compared to classical
anthropometric parameters of lean and obese children. METHODS: Three dimensional
(3D)-body scanning quantified anthropometric (height, weight, NC, hip/waist
circumference, BMI) and metabolic parameters (fasting plasma glucose [FPG],
insulin, HbA1c, oGTT, HOMA-IR) were determined cross-sectionally in 1542
participants (5-18 years). RESULTS: NC was positively correlated with all
metabolic parameters, except for FPG. For HbA1c there was only a modestly
positive correlation. The associations between NC and glucose parameters were
rather weak, while the correlation to insulin parameters were stronger. Overall
the strongest association to glucose metabolism parameters was found for waist
circumference (WC), except for FPG and 2h-postload glucose. In multiple linear
regression analyses, NC provided additional benefit beyond classical
anthropometric indices to describe impairment of glucose homeostasis.
CONCLUSIONS: We suggest that NC is comparable or additive to established
anthropometric parameters but might not be superior to them. However NC is simple
to measure, reproducible and may be considered in clinical practice as an
additional measurement tool.
PMID- 28489561
TI - 3D power Doppler in the evaluation of abnormally invasive placenta.
AB - The anomalies in placental insertion and invasion, such as placenta previa and
the various forms of abnormally invasive placenta, are today a rising obstetric
pathology. Two-dimensional (2D) ultrasonography is the gold standard in the
diagnosis of abnormally invasive placenta (AIP), but the important feto-maternal
impact of this pathology suggests the opportunity to employ all the available
diagnostic techniques, such as three-dimensional (3D) power Doppler. This
technique allows acquiring multiplanar images on coronal, axial and sagittal
planes and with a rotational technique, it permits visualizing the placenta
bladder interface more accurately. Consequently, it allows a better study of the
degree of bladder invasion, which is information that has a great impact on the
subsequent counseling and management. Thus, 3D power Doppler represents an
important technique complementary to 2D ultrasound in the diagnosis of AIP. The
aim of this paper is to illustrate the possible applications of this procedure,
referring to the main literature data.
PMID- 28489562
TI - Incidence of menopausal symptoms in postmenopausal breast cancer patients treated
with aromatase inhibitors.
AB - Aromatase inhibitors (AIs) are the standard of care for postmenopausal women with
estrogen receptor-positive breast cancer. Here, we performed a meta-analysis to
evaluate the occurrence of menopausal symptoms in breast cancer patients
receiving the AI therapy. Patients treated with AIs had an increased risk of all
grade arthralgia (1.63 [95% CI: 1.34-1.98]) and insomnia (1.24 [95% CI: 1.14
1.34]). The overall incidence of hot flashes, fatigue, arthralgia, sweating, and
insomnia in patients receiving AIs was 30.47% (95% CI: 25.51%-35.93%), 17.16%
(95% CI: 14%-20.85%), 17.91% (95% CI: 11.29%-27.22%), 14.64% (95% CI: 11.46%
18.52%), and 16.52% (95% CI: 12.45%-21.6 %), respectively. Both arthralgia (RR =
0.34, 95% CI: 0.16-0.75) and sweating (RR = 11.02, 95% CI: 4.11-29.57) differed
between patients with early- and advanced-stage breast cancer. Our findings
indicates that AIs are associated with a significant risk of developing
arthralgia and insomnia in breast cancer patients. Effective early detection and
management of menopausal symptoms would likely lead to safer use of AIs in breast
cancer patients.
PMID- 28489563
TI - Efficacy of fibrin glue versus sutures for attaching conjunctival autografts in
pterygium surgery: a systematic review with meta-analysis and trial sequential
analysis of evidence.
AB - Previous meta-analyses have been conducted to compare the efficacy of fibrin glue
(FG) versus sutures in pterygium surgery; however, additional clinical trials
have since been published. Therefore, we conducted an updated meta-analysis to
further explore the association between FG application in pterygium surgery, and
the recurrence rate, complication rate, and surgical duration. An electronic
literature search for eligible studies published before July 29, 2016 was
conducted across multiple databases. Odds ratios (ORs), standardized mean
difference (SMD), and 95% confidence intervals (CI) were calculated. Publication
bias of the included articles was evaluated by funnel plots. Differences in
recurrence rate and complication rate between the FG and suture groups were
evaluated in terms of OR with 95% CI, and SMD with 95% CI were used to estimate
the difference in surgical duration. Trial sequential analysis (TSA) was used to
determine whether the currently available evidence was sufficient and conclusive.
Twenty-four studies were included in this study. The pooled ORs for recurrence
rate and complication rate were 0.35 and 1.121, respectively. The pooled SMD for
surgical duration was -4.142. The TSA results indicated that evidence of the
effect was sufficient in the recurrence group and surgical duration group.
Although there was no difference in complication rate between FG and sutures, the
apparent advantages of FG over sutures are shorter surgical duration and greater
reduction in the recurrence rate of pterygium.
PMID- 28489564
TI - YY1 promotes HDAC1 expression and decreases sensitivity of hepatocellular
carcinoma cells to HDAC inhibitor.
AB - YY1 is a DNA-binding transcription factor and reported to be involved in cancer
progression. Histone deacetylase inhibitor (HDACi) could inhibit proliferation
and promote apoptosis of Hepatocellular carcinoma (HCC) cells. However, it is
unclear about the roles of YY1 in the sensitivity of HCC cells to HDACi. In this
study, firstly, we identified two drug-response profiles to HDACi in HCC cell
lines, while our results showed that HDAC1 expression was positively correlated
with YY1 in HCC cell lines and primary tumor tissues. Secondly, YY1 decreased the
sensitivity of HCC cells to HDACi in vitro and in vivo. Furthermore, we found
that YY1 promoted HDAC1 expression by binding to its promoter, while HDAC1 in
turn up-regulated the expression of YY1. In conclusion, our results showed that
YY1 could reduce the sensitivity of HCC cells to HDACi and might be a potential
therapeutic target in HCC.
PMID- 28489565
TI - Motifs in the amino-terminus of CENP-A are required for its accumulation within
the nucleus and at the centromere.
AB - Centromere protein A (CENP-A) is a variant of core histone H3 that marks the
centromere's location on the chromosome. The mechanisms that target the protein
to the nucleus and the centromere have not been defined. In this study, we found
that deletion of the first 53 but not the first 29 residues of CENP-A from the
amino-terminus, resulted in its cytoplasmic localization. Two motifs, R42R43R44
and K49R52K53K56, which are reported to be required for DNA contact in the
centromere nucleosome, were found to be critical for CENP-A nuclear accumulation.
These two motifs potentially mediated its interaction with Importin-beta but were
not involved in CENP-A centromeric localization. A third novel motif,
L60L61I62R63K64, was found to be essential for the centromeric accumulation of
CENP-A. The nonpolar hydrophobic residues L60L61I62, but not the basic residues
R63K64, were found to be the most important residues. A protein interaction assay
suggested that this motif is not involved in the interaction of CENP-A with its
deposition factors but potentially mediates its interaction with core histone H4
and CENP-B. Our study uncovered the role of the amino-terminus of CENP-A in
localization.
PMID- 28489567
TI - Eg5 inhibitor YL001 induces mitotic arrest and inhibits tumor proliferation.
AB - Eg5 is a kinesin spindle protein that controls chromosomal segregation in mitosis
and is thus a critical drug target for cancer therapy. We report the discovery of
a potent, selective inhibitor of Eg5 designated YL001. YL001 was obtained through
shape similarity based virtual screening, and it bears a 1,5-disubstituted
tetrazole scaffold. YL001 exhibits favorable bioactivity in a variety of cancer
cell lines, including taxol-resistant ovarian cancer and 6TG-resistant breast
cancer cell lines. This compound inhibits tumor growth by 60% and significantly
prolongs median survival time by more than 50% in a xenograft mouse model. YL001
blocks the ATPase activity of Eg5 and causes mitotic failure, ultimately
resulting in apoptosis of cancer cells through activation of the caspase-3
pathway. Our findings demonstrate that YL001 is a potent antitumor agent that may
be developed for cancer therapeutics.
PMID- 28489568
TI - Efficacy and safety of decitabine in treatment of elderly patients with acute
myeloid leukemia: A systematic review and meta-analysis.
AB - Elderly patients with acute myeloid leukemia (AML) have limited treatment options
concerned about their overall fitness and potential treatment related mortality.
Although a number of clinical trials demonstrated benefits of decitabine
treatment in elderly AML patients, the results remains controversial. A meta
analysis was performed to evaluate efficacy and safety of decitabine in treatment
of elderly AML patients. Eligible studies were identified from PubMed, Web of
Science, Embase and Cochrane Library. Nine published studies were included in the
meta-analysis, enrolling 718 elderly AML patients. The efficacy outcomes were
complete remission (CR), overall response rate (ORR) and overall survival (OS).
Safety was evaluated based on treatment related grades 3-4 adverse events (AEs)
and early death (ED) rate. Pooled estimates with 95% confidence interval (CI) for
CR, ORR and OS were 27% (95% CI 19%-36%), 37% (95% CI 28%-47%) and 8.09 months
(95% CI 5.77-10.41), respectively. The estimated treatment related early death
(ED) incidences were within 30-days 7% (95% CI 2%-11%) and 60-days 17% (95% CI
11%-22%), respectively. Thrombocytopenia was the most common grades 3-4 AEs.
Subgroup analyses of age, cytogenetics risk, AML type and bone marrow blast
percentage showed no significant differences of treatment response to decitabine.
In conclusion, decitabine is an effective and well-tolerated therapeutic
alternative with acceptable side effects in elderly AML patients.
PMID- 28489569
TI - Statin use and survival outcomes in endocrine-related gynecologic cancers: A
systematic review and meta-analysis.
AB - Previous studies investigating the association between statin use and survival
outcomes in gynecologic cancers have yielded controversial results. We conducted
a systematic review and meta-analysis to evaluate the association based on
available evidence. We searched the databases of the Cochrane Central Register of
Controlled Trials (CENTRAL), Embase, and PubMed from inception to January 2017.
Studies that evaluated the association between statin use and survival outcomes
in gynecologic cancers were included. Pooled hazard ratios (HRs) for overall
survival, disease-specific survival and progression-free survival were calculated
using a fixed-effects model. A total of 11 studies involving more than 6,920
patients with endocrine-related gynecologic cancers were identified. In a meta
analysis of 7 studies involving 5,449 patients with endocrine-related gynecologic
cancers, statin use was linked to improved overall survival (HR, 0.71; 95%
confidence interval [CI], 0.63 to 0.80) without significant heterogeneity (I2 =
33.3%). Statin users also had improved disease-specific survival (3 studies, HR,
0.72; 95% CI, 0.58 to 0.90, I2 = 35.1%) and progression-free survival (3 studies,
HR, 0.68; 95% CI, 0.49 to 0.93, I2 = 33.6%) in endocrine-related gynecologic
cancers. Our findings support that statin use has potential survival benefits for
patients with endocrine-related gynecologic cancers. Further large-scale
prospective studies are required to validate our findings.
PMID- 28489570
TI - Transcriptome profiling identifies a recurrent CRYL1-IFT88 chimeric transcript in
hepatocellular carcinoma.
AB - We performed transcriptome sequencing for hepatocellular carcinoma (HCC) and
adjacent non-tumorous tissues to investigate the molecular basis of HCC. Nine HCC
patients were recruited and differentially expressed genes (DEGs) were
identified. Candidate fusion transcripts were also identified. A total of 1943
DEGs were detected, including 690 up-regulated and 1253 down-regulated genes, and
enriched in ten pathways including cell cycle, DNA replication, p53, complement
and coagulation cascades, etc. Seven candidate fusion genes were detected and
CRYL1-IFT88 was successfully validated in the discovery sequencing sample and
another 5 tumor samples with the recurrent rate of about 9.52% (6/63). The full
length of CRYL1-IFT88 was obtained by 3' and 5' RACE. The function of the fusion
transcript is closed to CRYL1 because it contained most of domain of CRYL1.
According to the bioinformatics analysis, IFT88, reported as a tumor suppressor,
might be seriously depressed in the tumor cell with this fusion because the
transcript structure of IFT88 was totally changed. The function depression of
IFT88 caused by gene fusion CRYL1-IFT88 might be associated with tumorigenesis or
development of HCC.
PMID- 28489571
TI - Analysis of STAT3 post-translational modifications (PTMs) in human prostate
cancer with different Gleason Score.
AB - Prostate Cancer (PCa) is a complex and heterogeneous disease. The androgen
receptor (AR) and the signal transducer and activator of transcription 3 (STAT3)
could be effective targets for PCa therapy. STAT3, a cytoplasmatic latent
transcription factor, is a hub protein for several oncogenic signalling pathways
and up-regulates the expression of numerous genes involved in tumor cell
proliferation, angiogenesis, metastasis and cell survival. STAT3 activity can be
modulated by several Post-Translational Modifications (PTMs) which reflect
particular cell conditions and may be implicated in PCa development and
progression. The aim of this work was to analyze STAT3 PTMs at different tumor
stages and their relationship with STAT3 cellular functions. For this purpose,
sixty-five prostatectomy, Formalin-fixed paraffin-embedded (FFPE) specimens,
classified with different Gleason Scores, were subjected to immunoblotting,
immunofluorescence staining and RT-PCR analysis. All experiments were carried out
in matched non-neoplastic and neoplastic tissues. Data obtained showed different
STAT3 PTMs profiles among the analyzed tumor grades which correlate with
differences in the amount and distribution of specific STAT3 interactors as well
as the expression of STAT3 target genes. These results highlight the importance
of PTMs as an additional biomarker for the exactly evaluation of the PCa stage
and the optimal treatment of this disease.
PMID- 28489573
TI - Recombinant SjP40 protein enhances p27 promoter expression in hepatic stellate
cells via an E2F1-dependent mechanism.
AB - The p27 protein plays a critical role in cell cycle arrest. Our previous studies
have demonstrated that recombinant P40 protein from Schistosoma japonicum
(rSjP40) could induce G1 phase arrest of cell cycle. We, therefore, attempted to
observe the effect of rSjP40 on p27 promoter activity in LX-2 cells and to
explore its potential mechanisms in this study. Using both Western blot and dual
luciferase reporter assay, we demonstrated that rSjP40 could enhance the
expression of p27 in LX-2 cells. Results obtained using truncated fragments of
p27 promoter showed that rSjP40 increased p27 promoter activity in LX-2 cells,
mainly via some transcription factors that bind to the -1740/-873 region of p27
promoter. Further studies confirmed that the enhancement of p27 promoter activity
induced by rSjP40 was related to E2F1 in LX-2 cells. Transfection of siRNA of
E2F1 could also restore the effect of rSjP40 on expression of p27 and partially
on alpha-SMA. Therefore, our study provided further insights into the mechanism
by which rSjP40 induces LX-2 cell cycle arrest at G1 phase and inhibits HSC
activation. Our results provide basis for future study of the blocking effect of
rSjP40 in liver fibrosis.
PMID- 28489572
TI - CK2 and PI3K are direct molecular targets of quercetin in chronic lymphocytic
leukaemia.
AB - Despite the encouraging results of the innovative therapeutic treatments,
complete remission is uncommon in patients affected by chronic lymphocytic
leukaemia, which remains an essentially incurable disease. Recently, clinical
trials based on BH3-mimetic drugs showed positive outcomes in subjects with poor
prognostic features. However, resistance to treatments occurs in a significant
number of patients. We previously reported that the multi-kinase inhibitor
quercetin, a natural flavonol, restores sensitivity to ABT-737, a BH3-mimetic
compound, in both leukemic cell lines and B-cells isolated from patients. To
identify the molecular target of quercetin, we employed a new cell line, HG3,
obtained by immortalization of B-cells from a chronic lymphocytic leukaemia
patient at the later stage of disease. We confirmed that quercetin in association
with ABT-737 synergistically enhances apoptosis in HG3 (combination index < 1 for
all fractions affected). We also reported that the cellular uptake of quercetin
is extremely rapid, with an intracellular concentration of about 38.5 ng/106
cells, after treatment with 25 MUM for 5 min. We demonstrated that the activity
of protein kinase CK2, which positively triggers PI3K/Akt pathway by inactivating
PTEN phosphatase, is inhibited by quercetin immediately after its addition to HG3
cells (0-2 min). PI3K activity was also inhibited by quercetin within 60 min from
the treatment. The combined inhibition of CK2 and PI3K kinase activities by
quercetin restored ABT-737 sensitivity and increased lethality in human leukemia
cells.
PMID- 28489574
TI - Targeting neurokinin-3 receptor: a novel anti-angiogenesis strategy for cancer
treatment.
AB - Angiogenesis is essential for tumor growth and metastasis, controlling
angiogenesis is a promising strategy in cancer treatment. However, thus farther
severe side effects of anti-angiogenic drugs have been rather demonstrated,
stimulating interest in seeking novel targets of anti-angiogenesis. Neurokinin
receptors, also known as tachykinin receptors, are usually considered as drug
targets due to diverse physiological functions and their tractability. Although
Neurokinin B, the selective natural agonist of neurokinin-3 receptor, have been
shown to exhibit anti-angiogenesis activity, the effect and mechanism of
neurokinin-3 receptor-mediated angiogenesis still remains unclear. In the present
study, we demonstrated that [Mephe7]NKB, an analogue of NKB, possess significant
anti-angiogenic effect on CAM. Furthermore, by introducing the tumor angiogenesis
homing sequence (NGR), we designed and synthesized two novel agonist analogues of
NK3R, NK3R-A1 and NK3R-A2. Both of the two analogues exhibit more efficient anti
migration effect on HUVECs by activating NK3R in vitro, and showed potent
antitumor activities with no significant side effects in vivo. Taken together,
our results illuminated that NK3R might be a potential novel target for the anti
angiogenesis therapy. Notably, NK3R-A1 might be used as a template for the
development of the anti-tumor drugs on the basis of the anti-angiogenesis
strategy.
PMID- 28489575
TI - Evaluation of 99mTc-HYNIC-MPG as a novel SPECT radiotracer to detect EGFR
activating mutations in NSCLC.
AB - Tyrosine kinase inhibitors (EGFR-TKIs) targeting the epidermal growth factor
receptor (EGFR) have been used in non-small cell lung carcinoma (NSCLC) for years
with promising results, in particular in patients with activating mutations in
the EGFR kinase domain (exon 19 E746-A750 deletion or exon 21 L858R point
mutation). However, despite their great success in the clinic, a significant
number of patients do not respond to EGFR-TKIs, such as those carrying the
L858R/T790M mutation or EGFR wild type. Thus, detecting the EGFR mutation status
before EGFR-TKIs therapy is essential to ensure its efficacy. In this study, we
report a novel SPECT tracer 99mTc-HYNIC-MPG that binds specifically to activating
mutant EGFR and which could therefore be used to noninvasively select patients
sensitive to EGFR-TKIs. We evaluated the capacity of 99mTc-HYNIC-MPG in detecting
EGFR-activating mutations both in vitro and in vivo using four human NSCLC cell
lines (PC9, H1975, H358 and H520). 99mTc-HYNIC-MPG had significantly higher
accumulation in PC9 tumor cells when compared to H1975, H358 and H520 tumors
cells, which may be due to the activating mutations (exon 19 deletion) in EGFR
tyrosine kinase domain in PC9 cells. Thus, 99mTc-HYNIC-MPG SPECT imaging may be
used to identify NSCLC tumors with a potential high response rate to EGFR-TKIs.
PMID- 28489576
TI - Intraoperative contrast-enhanced ultrasonography for microcirculatory evaluation
in rhesus monkey with spinal cord injury.
AB - This study tried to quantify spinal cord perfusion by using contrast-enhanced
ultrasound (CEUS) in rhesus monkey models with acute spinal cord injury. Acute
spinal cord perfusion after injury was detected by CEUS, coupling with
conventional ultrasound (US) and Color Doppler US (CDFI). Time-intensity curves
and perfusion parameters were obtained by autotracking contrast quantification
(ACQ) software in the epicenter and adjacent regions of injury, respectively.
Neurological and histological examinations were performed to confirm the severity
of injury. US revealed spinal cords were hypoechoic and homogeneous, whereas dura
maters, pia maters, and cerebral aqueducts were hyperechoic. After spinal cord
contusion, the injured spinal cord was hyperechoic on US, and intramedullary
vessels of adjacent region of injury were increased and dilated on CDFI. On CEUS
hypoperfusion were found in the epicenter of injury, while hyperperfusion in its
adjacent region. Quantitative analysis showed that peak intensity (PI) decreased
in epicenters of injury but significantly increased in adjacent regions at all
time points (p < 0.05). Functional evaluation demonstrated significant
deterioration compared to pre-contusion (p < 0.05). Quantitative analysis with
CEUS is a promising method for monitoring perfusion changes of spinal cord injury
in overall views and real-time.
PMID- 28489577
TI - Pancreatic cancer ascites xenograft-an expeditious model mirroring advanced
therapeutic resistant disease.
AB - Pancreatic ductal adenocarcinoma has limited treatment options. There is an
urgent need for developing appropriate pre-clinical models recapitulating
metastatic disease, the most common clinical scenario at presentation. Ascites
accumulation occurs in up to 20-30% of patients with pancreatic cancer; this
milieu represents a highly cellular research resource of metastatic peritoneal
spread. In this study, we utilized pancreatic ascites/pleural effusion cancer
cells to establish patient derived xenografts.Ascites/pleural effusion-patient
derived xenografts were established from twelve independent cases. Xenografts
were serially passed in nude mice and tissue bio-specimen banking has been
established. Histopathology of emergent tumors demonstrates poorly to moderately
differentiated, glandular and mucin producing tumors, mirroring morphology of
primary pancreatic cancer tumors. Whole genome sequencing of six patient derived
xenografts samples demonstrates common mutations and structural variations
similar to those reported in primary pancreatic cancer. Xenograft tumors were
dissociated to single-cells and in-vitro drug sensitivity screen assays
demonstrated chemo-resistance, correlating with patient clinical scenarios, thus
serving as a platform for clinically relevant translational research.Therefore,
establishment of this novel ascites/pleural effusion patient derived xenograft
model, with extensive histopathology and genomic characterization, opens an
opportunity for the study of advanced aggressive pancreatic cancer.
Characterization of metastatic disease and mechanisms of resistance to
therapeutics may lead to the development of novel drug combinations.
PMID- 28489578
TI - Inhibiting translesion DNA synthesis as an approach to combat drug resistance to
DNA damaging agents.
AB - Anti-cancer agents exert therapeutic effects by damaging DNA. Unfortunately, DNA
polymerases can effectively replicate the formed DNA lesions to cause drug
resistance and create more aggressive cancers. To understand this process at the
cellular level, we developed an artificial nucleoside that visualizes the
replication of damaged DNA to identify cells that acquire drug resistance through
this mechanism. Visualization is achieved using "click" chemistry to covalently
attach azide-containing fluorophores to the ethynyl group present on the
nucleoside analog after its incorporation opposite damaged DNA. Flow cytometry
and microscopy techniques demonstrate that the extent of nucleotide incorporation
into genomic DNA is enhanced by treatment with DNA damaging agents. In addition,
this nucleoside analog inhibits translesion DNA synthesis and synergizes the
therapeutic activity of certain anti-cancer agents such as temozolomide. The
combined diagnostic and therapeutic activities of this synthetic nucleoside
analog represent a new paradigm in personalized medicine.
PMID- 28489580
TI - Rapamycin regulates macrophage activation by inhibiting NLRP3 inflammasome-p38
MAPK-NFkappaB pathways in autophagy- and p62-dependent manners.
AB - Excessive and prolonged activation of macrophages underlies many inflammatory and
autoimmune diseases. To regulate activation and maintain homeostasis, macrophages
have multiple intrinsic mechanisms, one of which is modulation through autophagy.
Here we demonstrate that autophagy induction by rapamycin suppressed the
production of IL-1beta and IL-18 in lipopolysaccharide- and adenosine
triphosphate-activated macrophages at the post-transcriptional level by
eliminating mitochondrial ROS (mtROS) and pro-IL1beta in a p62/SQSTM1-dependent
manner. In addition, rapamycin activated Nrf2 through up-regulation of
p62/SQSTM1, which further contributed to the reduction of mtROS. Reduced IL-1beta
subsequently diminished the activation of p38 MAPK-NFkappaB pathways, leading to
transcriptional down-regulation of IL-6, IL-8, MCP-1, and IkappaBalpha in
rapamycin-treated macrophages. Therefore, our results suggest that rapamycin
negatively regulates macrophage activation by restricting a feedback loop of
NLRP3 inflammasome-p38 MAPK-NFkappaB pathways in autophagy- and p62/SQSTM1
dependent manners.
PMID- 28489581
TI - High glucose induces formation of tau hyperphosphorylation via Cav-1-mTOR
pathway: A potential molecular mechanism for diabetes-induced cognitive
dysfunction.
AB - The abnormally hyperphosphorylated tau is thought to be implicated in diabetes
associated cognitive deficits. The role of mammalian target of rapamycin (mTOR) /
S6 kinase (S6K) signalling in the formation of tau hyperphosphorylation has been
previously studied. Caveolin-1 (Cav-1), the essential structure protein of
caveolae, promotes neuronal survival and growth, and inhibits glucose metabolism.
In this study, we aimed to investigate the role of Cav-1 in the formation of tau
hyperphosphorylation under chronic hyperglycemic condition (HGC). Diabetic rats
were induced by streptozotocin (STZ). Primary hippocampal neurons with or without
molecular intervention such as the transient over-expression or knock-down were
subjected to HGC. The obtained experimental samples were analyzed by real time
quantitative RT-PCR, Western blot, immunofluorescence or immunohistochemisty. We
found: 1) that a chronic HGC directly decreases Cav-1 expression, increases tau
phosphorylation and activates mTOR/S6K signalling in the brain neurons of
diabetic rats, 2) that overexpression of Cav-1 attenuates tau
hyperphosphorylation induced by chronic HGC in primary hippocampal neurons,
whereas down-regulation of Cav-1 using Cav-1 siRNA dramatically worsens tau
hyperphosphorylation via mTOR/S6K signalling pathway, and 3) that the down
regulation of Cav-1 induced by HGC is independent of mTOR signalling. Our results
suggest that tau hyperphosphorylation and the sustained over-activated mTOR
signalling under hyperglycemia may be due to the suppression of Cav-1. Therefore,
Cav-1 is a potential therapeutic target for diabetes-induced cognitive
dysfunction.
PMID- 28489583
TI - Association between vascular endothelial growth factor gene polymorphisms and the
risk and prognosis of renal cell carcinoma: A systematic review and meta
analysis.
AB - The aim of the meta-analysis was to clarify the associations between vascular
endothelial growth factor (VEGF) polymorphisms and the risk and prognosis of
renal cell carcinoma (RCC). A meta-analysis was performed by searching the
databases PubMed, EMBASE and Web of Science for the relevant available studies
until August 1st, 2016, and fourteen studies met the inclusion criteria. The
pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to
evaluate the strength of such associations. Besides, the pooled hazard ratios
(HRs) with 95% CIs were used to evaluate the overall survival (OS). Fixed- or
random-effects models were conducted according to existence of heterogeneity.
Publication bias was evaluated using Begg's funnel plots and Egger's regression
test. Overall, this meta-analysis included a total of 8,275 patients, who had
been accrued between November 2002 and September 2015. Meta-analysis indicated
that -2578C/A, +936C/T and +405G/C polymorphisms in the VEGF gene correlated with
elevated RCC risk, especially in Asian populations. Moreover, VEGF -1154G/A and
634C/G polymorphisms were found significantly associated with poor OS of RCC.
Therefore, this meta-analysis revealed that VEGF -2578C/A, +936C/T, +405G/C
polymorphisms were associated with an elevated susceptibility to RCC, indicating
that these three polymorphisms might be risk factors for RCC, especially in Asian
populations.
PMID- 28489582
TI - Association between the ERCC2 Asp312Asn polymorphism and risk of cancer.
AB - Cancer is the leading cause of death in economically developed countries and the
second leading cause of death in developing countries. The relationship between
genetic polymorphisms and the risk of cancers has been widely researched.
Excision repair cross-complementing group 2 (ERCC2) gene plays important roles in
the nucleotide excision repair pathway. There is contrasting evidence on the
association between the ERCC2 Asp312Asn polymorphism and the risk of cancer. We
conducted a comprehensive meta-analysis in order to assess the correlation
between these factors. We searched the PubMed, EMBASE, Science Direct, Web of
Science, and CNKI databases for studies published from January 1, 2005 to January
1, 2016. Finally, 86 articles with 38,848 cases and 48,928 controls were included
in the analysis. The overall analysis suggested a significant association between
the ERCC2 Asp312Asn polymorphism and cancer risk. Furthermore, control source,
ethnicity, genotyping method, and cancer type were used for subgroup analysis.
The result of a trial sequential analysis indicated that the cumulative evidence
is adequate; hence, further trials were unnecessary in the overall analysis for
homozygote comparison. In summary, our results suggested that ERCC2 Asp312Asn
polymorphism is associated with increased cancer risk. A significantly increased
cancer risk was observed in Asian populations, but not in Caucasian populations.
Furthermore, the ERCC2 Asp312Asn polymorphism is associated with bladder,
esophageal, and gastric cancers, but not with breast, head and neck, lung,
prostate, and skin cancers, and non-Hodgkin lymphoma. Further multi-center, well
designed studies are required to validate our results.
PMID- 28489584
TI - Transcriptional response profiles of paired tumor-normal samples offer novel
perspectives in pan-cancer analysis.
AB - Both tumor and adjacent normal tissues are valuable in cancer research.
Transcriptional response profiles represent the changes of gene expression levels
between paired tumor and adjacent normal tissues. In this study, we performed a
pan-cancer analysis based on the transcriptional response profiles from 633
samples across 13 cancer types. We obtained two interesting results. Using
consensus clustering method, we characterized ten clusters with distinct
transcriptional response patterns and enriched pathways. Notably, head and neck
squamous cell carcinoma was divided in two subtypes, enriched in cell cycle
related pathways and cell adhesion-related pathways respectively. The other
interesting result is that we identified 92 potential pan-cancer genes that were
consistently upregulated across multiple cancer types. Knockdown of FAM64A or
TROAP inhibited the growth of cancer cells, suggesting that these genes may
promote tumor development and are worthy of further validations. Our results
suggest that transcriptional response profiles of paired tumor-normal tissues can
provide novel perspectives in pan-cancer analysis.
PMID- 28489585
TI - POU2F1 over-expression correlates with poor prognoses and promotes cell growth
and epithelial-to-mesenchymal transition in hepatocellular carcinoma.
AB - Despite recent efforts to understand activities of POU domain class 2
transcription factor 1 (POU2F1), little is known about the roles of POU2F1 in
hepatocellular carcinoma (HCC) tumorigenesis and its correlation with any
clinicopathological feature of HCC. In this study, we found that POU2F1 was
significantly up-regulated in HCC specimens compared with adjacent non-cancerous
liver specimens. The high POU2F1 protein expression level positively correlated
with large tumor size, high histological grade, tumor metastasis and advanced
clinical stage, and HCC patients with high POU2F1 levels exhibited poor
prognoses. We further demonstrated that POU2F1 over-expression promoted HCC cell
proliferation, colony formation, epithelial-to-mesenchymal transition (EMT),
migration and invasion, while silencing of POU2F1 inhibited these malignant
phenotypes. POU2F1 induced the expression of Twist1, Snai1, Snai2 and ZEB1 genes
which are involved in the regulation of EMT. Furthermore, POU2F1 was up-regulated
by AKT pathway in HCC, and POU2F1 over-expression reversed the inhibition of
malignant phenotypes induced by AKT knock-down, indicating POU2F1 is a key down
stream effector of AKT pathway. Collectively, our results indicate that POU2F1
over-expression is positively associated with aggressive phenotypes and poor
survival in patients with HCC, and POU2F1 regulated by AKT pathway promotes HCC
aggressive phenotypes by regulating the transcription of EMT genes. POU2F1 may be
employed as a new prognostic factor and therapeutic target for HCC.
PMID- 28489586
TI - Ephrin-B2/Fc promotes proliferation and migration, and suppresses apoptosis in
human umbilical vein endothelial cells.
AB - Tumor growth and metastasis are angiogenesis dependent. Angiogenic growth
involves endothelial cell proliferation, migration, and invasion. Ephrin-B2 is a
ligand for Eph receptor tyrosine kinases and is an important mediator in vascular
endothelial growth factor-mediated angiogenesis. However, research offer
controversial information regarding effects of ephrin-B2 on vascular endothelial
cells. In this paper, proteome analyses showed that ephrin-B2/Fc significantly
activates multiple signaling pathways related to cell proliferation, survival,
and migration and suppresses apoptosis and cell death. Cytological experiments
further confirm that ephrin-B2/Fc stimulates endothelial cell proliferation,
triggers dose-dependent migration, and suppresses cell apoptosis. Results
demonstrate that soluble dose-dependent ephrinB2 can promote proliferation and
migration and inhibit apoptosis of human umbilical vein endothelial cells. These
results also suggest that ephrinB2 prevents ischemic disease and can potentially
be a new therapeutic target for treating angiogenesis-related diseases and
tumors.
PMID- 28489587
TI - NGS based identification of mutational hotspots for targeted therapy in
anaplastic thyroid carcinoma.
AB - CONTEXT: Anaplastic thyroid carcinoma (ATC) represents one of the most aggressive
carcinomas with no consistent survival benefit when treated with conventional
radiochemotherapy. Approaches targeting "oncogene addiction" of ATC are
increasingly explored and first promising results have been reported in single
case studies. OBJECTIVE: To determine the prevalence of mutations in known
thyroid oncogenes and signalling pathways amendable to targeted therapy in a
large cohort of ATC. RESULTS: In 118 ATC (57 male/ 61 female) a total of 165
mutations were found. Genes involved in the MAPK/ERK and PI3K pathway (BRAF
11.0%, HRAS 4.2%, KRAS 7.6%, NRAS 7.6%, PI3KCA 11.8%) were altered in 33%.
Targetable receptor tyrosine kinases were mutated in 11%. The most frequently
altered genes were TERT in 86/118 (73%) and p53 in 65/118 (55%) cases. No
mutations were found analysing ALK, KIT, MET and mTOR. MATERIALS AND METHODS:
Next generation sequencing (NGS) was performed in FFPE samples from 118 ATC using
MiSeq (Illumina) and CLC Cancer Research Workbench (CLCbio; Qiagen) for mutation
analysis in: ALK, BRAF, CDKN2A, EGFR, ERBB2, HRAS, KIT, KRAS, MET, mTOR, NRAS,
PDGFRA, PI3KCA, p53, RB1, RET and TSC2. Sanger sequencing was used to detect TERT
promotor mutations. CONCLUSIONS: To our knowledge this is the largest study
analysing mutations for targeted therapy of ATC. We found that 33% of ATC harbour
mutations in pathways amendable to targeted therapy. Molecular screening in ATC
is suggested for targeted therapies since current conventional treatment for ATC
proved mainly futile.
PMID- 28489589
TI - Inhibitory effect of ethanol extract of Nannochloropsis oceanica on
lipopolysaccharide-induced neuroinflammation, oxidative stress, amyloidogenesis
and memory impairment.
AB - Oxidative stress and neuroinflammation is implicated in the pathogenesis and
development of Alzheimer's disease (AD). Here, we investigated the suppressive
possibility of ethanol extract of Nannochloropsis oceanica (N. oceanica) on
memory deficiency along with the fundamental mechanisms in lipopolysaccharide
(LPS)-treated mice model. Among several extracts of 32 marine microalgae, ethanol
extract of N. oceanica showed the most significant inhibitory effect on nitric
oxide (NO) generation, NF-kappaB activity and beta-secretase activity in cultured
BV-2 cells, neuronal cells and Raw 264.7 cells. Ethanol extract of N. oceanica
(50, 100 mg/kg) also ameliorated LPS (250 MUg/kg)-induced memory impairment. We
also found that ethanol extract of N. oceanica inhibited the LPS-induced
expression of iNOS and COX-2. Furthermore, the production of reactive oxygen
species (ROS), malondialdehyde (MDA) level as well as glutathione (GSH) level was
also decreased by treatment of ethanol extract of N.oceanica. The ethanol extract
of N. oceanica also suppresses IkappaB degradation as well as p50 and p65
translocation into the nucleus in LPS-treated mice brain. Associated with the
inhibitory effect on neuroinflammation and oxidative stress, ethanol extract of
N. oceanica suppressed Abeta1-42 generation through down-regulation of APP and
BACE1 expression in in vivo. These results suggest that ethanol extract of N.
oceanica ameliorated memory impairment via anti-inflammatory, anti-oxidant and
anti-amyloidogenic mechanisms.
PMID- 28489590
TI - Polymorphisms of VDR gene and risk of gastric cardiac adenocarcinoma in Chinese
population.
AB - Vitamin D receptor (VDR) gene polymorphisms have been reported to increase
susceptibility to some malignant tumors, yet the effect on gastric cardiac
adenocarcinoma susceptibility remains unknown. Here, we conducted a hospital
based case-control study to examine the correlation of single nucleotide
polymorphisms of VDR rs2107301T>C, rs2228570C>T, rs1989969C>T and rs11568820 G>A
and gastric cardiac adenocarcinoma susceptibility. A total 330 cases and 608
controls were enrolled in the study. Using ligation detection reaction, we found
that the variant alleles of the four polymorphisms were not associated with risk
of gastric cardiac adenocarcinoma. Further stratified analyses showed that there
was an increased risk associated with VDR rs1989969 polymorphism among patients
who were drinking or aged <60. The haplotypes VDR
Trs2107301Trs2228570Crs1989969Grs11568820 reduced the susceptibility. This study
demonstrated that VDR rs1989969 polymorphism was involved in the carcinogenesis
of gastric cardiac adenocarcinoma, especially increased the risk in the younger
and alcohol drinking Chinese population.
PMID- 28489591
TI - Molecular characterization of circulating tumor cells from patients with
metastatic breast cancer reflects evolutionary changes in gene expression under
the pressure of systemic therapy.
AB - Resistance to systemic therapy is a major problem in metastatic breast cancer
(MBC) that can be explained by initial tumor heterogeneity as well as by
evolutionary changes during therapy and tumor progression. Circulating tumor
cells (CTCs) detected in a liquid biopsy can be sampled and characterized
repeatedly during therapy in order to monitor treatment response and disease
progression.Our aim was to investigate how CTC derived gene expression of
treatment predictive markers (ESR1/HER2) and other cancer associated markers
changed in patient blood samples during six months of first-line systemic
treatment for MBC. CTCs from 36 patients were enriched using CellSearch (Janssen
Diagnostics) and AdnaTest (QIAGEN) before gene expression analysis was performed
with a customized gene panel (TATAA Biocenter).Our results show that antibodies
against HER2 and EGFR were valuable to isolate CTCs unidentified by CellSearch
and possibly lacking EpCAM expression. Evaluation of patients with clinically
different breast cancer subgroups demonstrated that gene expression of treatment
predictive markers changed over time. This change was especially prominent for
HER2 expression.In conclusion, we found that changed gene expression during first
line systemic therapy for MBC could be a possible explanation for treatment
resistance. Characterization of CTCs at several time-points during therapy could
be informative for treatment selection.
PMID- 28489596
TI - Lymph nodes ratio based nomogram predicts survival of resectable gastric cancer
regardless of the number of examined lymph nodes.
AB - To develop a nomogram to predict the prognosis of gastric cancer patients on the
basis of metastatic lymph nodes ratio (mLNR), especially in the patients with
total number of examined lymph nodes (TLN) less than 15. The nomogram was
constructed based on a retrospective database that included 2,205 patients
underwent curative resection in Cancer Center, Sun Yat-sen University (SYSUCC).
Resectable gastric cancer (RGC) patients underwent curative resection before
December 31, 2008 were assigned as the training set (n=1,470) and those between
January 1, 2009 and December 31, 2012 were selected as the internal validation
set (n=735). Additional external validations were also performed separately by an
independent data set (n=602) from Jiangxi Provincial Cancer Hospital (JXCH) in
Jiangxi, China and a data set (n=3,317) from the Surveillance, Epidemiology, and
End Results (SEER) database. The Independent risk factors were identified by
Multivariate Cox Regression. In the SYSUCC set, TNM (Tumor-node-metastasis) and
TRM-based (Tumor-Positive Nodes Ratio-Metastasis) nomograms were constructed
respectively. The TNM-based nomogram showed better discrimination than the AJCC
TNM staging system (C-index: 0.73 versus 0.69, p<0.01). When the mLNR was
included in the nomogram, the C-index increased to 0.76. Furthermore, the C-index
in the TRM-based nomogram was similar between TLN >=16 (C-index: 0.77) and TLN
<=15 (C-index: 0.75). The discrimination was further ascertained by internal and
external validations. We developed and validated a novel TRM-based nomogram that
provided more accurate prediction of survival for gastric cancer patients who
underwent curative resection, regardless of the number of examined lymph nodes.
PMID- 28489599
TI - Association between the p.V37I variant of GJB2 and hearing loss: a pedigree and
meta-analysis.
AB - Pathogenic variants in the gap junction protein beta-2 (GJB2) gene are the most
common cause of hearing loss. Of these, the p.V37I variant of GJB2 has a high
allele frequency (up to 10%) in East Asians. Characterization of the phenotypic
spectrum associated with p.V37I, as well as the role of this variant in the onset
of hearing loss could have a remarkable effect on future diagnostic strategies.
Here, we performed a pedigree analysis of unrelated families exhibiting various
hearing phenotypes, and then conducted a meta-analysis to comprehensively assess
the association between the p.V37I and the risk of hearing loss. Pedigree
analyses showed that both homozygous p.V37I variants, as well as compound
heterozygous p.V37I with other GJB2 pathogenic variants, contributed to various
phenotypes of hearing loss. Meanwhile, meta-analysis demonstrated that, compared
with those in the wild type group, both p.V37I homozygotes and compound
heterozygous p.V37I variants were at significantly higher risk of developing
hearing loss (odds ratios = 7.14 and 3.63; 95% confidence intervals = 3.01-16.95
and 1.38-9.54, respectively). Conversely, heterozygous p.V37I variants alone did
not increase the risk of hearing loss. Given the high allele carriage rate of
p.V37I (up to 10%) within the general population, our work not only provides
information that might influence future genetic screening policies, but also
offers insight into clinical risk evaluation and genetic counseling regarding
hearing loss.
PMID- 28489600
TI - Oleate-induced PTX3 promotes head and neck squamous cell carcinoma metastasis
through the up-regulation of vimentin.
AB - The association between metabolic diseases and the risk of developing cancer is
emerging. However, the impact of long pentraxin-3 (PTX3) on dyslipidemia
associated tumor metastasis remains unknown. In this study, we found that oleate
induced PTX3 expression and secretion through the activation of Akt/NF-kappaB
pathway in head and neck squamous cell carcinomas (HNSCCs). The activation of NF
kappaB was essential for the oleate-induced stabilization of PTX3 mRNA. In
addition, both the depletion of PTX3 and the inhibition of NF-kappaB
significantly inhibited oleate-induced tumor cell migration and invasion. The
enhancement of binding between tumor and endothelial cells was observed in oleate
treated cells but not in the depletion and neutralization of PTX3 with siPTX3 and
anti-PTX3 antibodies, respectively. The levels of oleate-induced epithelial
mesenchymal transition (EMT) markers, such as vimentin and MMP-3, were
significantly reduced in PTX3-depleted cells. Knocking down vimentin also
repressed oleate-induced HNSCC invasion. Furthermore, the depletion of PTX3
blocked the oleate-primed metastatic seeding of tumor cells in the lungs. These
results demonstrate that oleate enhances HNSCC metastasis through the
PTX3/vimentin signaling axes. The inhibition of PTX3 could be a potential
strategy for the treatment of dyslipidemia-mediated HNSCC metastasis.
PMID- 28489602
TI - Elevated serum growth differentiation factor 15 levels are associated with
thyroid nodules in type 2 diabetes aged over 60 years.
AB - In order to investigate whether serum growth differentiation factor 15 is
associated with thyroid nodules in type 2 diabetes. We recruited 723 type 2
diabetic patients aged over 30 years who attended the clinic of Endocrinology of
Xinhua Hospital from January 2013 to January 2015. Thyroid nodule was diagnosed
by thyroid ultrasonographic examination. Serum growth differentiation factor 15,
thyroid function, thyroid autoantibodies, thyroglobulin and other biochemical
indicators were measured and compared between thyroid nodule positive and
negative groups. We found that overall, serum growth differentiation factor 15
levels were significantly higher in subjects with thyroid nodules compared with
nodule negative subjects (181.76+/-98.49 pg/ml vs. 162.32+/-83.63 pg/ml, p<0.05),
and this was influenced by age. In the patients over 60 years, this difference
became more significant (211.23+/-103.66 pg/ml vs. 177.38+/-85.51 pg/ml, p<0.01),
but in patients under 60 years, there was no difference between the two groups.
Multivariate logistic regression analysis showed that serum growth
differentiation factor 15 levels were independently associated with thyroid
nodule in diabetic patients over 60 years (P <0.001). After multiple adjustments,
the odds ratios were substantially higher for thyroid nodule (odds ratio 2.63,
95% confidence interval 1.30-5.13, p<0.01) in the highest growth differentiation
factor 15 quartile compared to those in the lowest quartile in patients over 60
years. In conclusion, serum growth differentiation factor 15 is increased
significantly in subjects with thyroid nodules in type 2 diabetic patients aged
over 60 years.
PMID- 28489603
TI - 18F-fluorodeoxyglucose uptake predicts PKM2 expression in lung adenocarcinoma.
AB - Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) is
widely used in the management of lung adenocarcinoma. Pyruvate kinase M2 (PKM2)
plays a key role in glycolysis. We therefore investigated whether PKM2 expression
affects 18F-FDG uptake in a retrospective analysis of 76 patients who underwent
18F-FDG PET/computed tomography (CT) scans for staging before surgical resection.
We found that PKM2 expression was higher in tumors than peritumoral tissue (p <
0.05). Patients with high PKM2 expression had reduced overall (p < 0.05) and
disease-free (p < 0.05) survival as compared to those with low PKM2 expression.
Comparison of the primary tumor maximum standardized uptake value (SUVmax)
between patients with high and low PKM2 expression revealed that the SUVmax was
higher in primary tumors with high PKM2 expression than low PKM2 expression (p <
0.05). Multivariate analysis confirmed the association between SUVmax and PKM2
expression (p < 0.05). PKM2 status was predicted with 81.6% accuracy when the
SUVmax cutoff value of 6.4. Thus,18F-FDG PET/CT is predictive of the PKM2 status
in lung adenocarcinoma patients and could aid in determining therapeutic
strategies.
PMID- 28489604
TI - Prevalence of primary cardiac tumor malignancies in retrospective studies over
six decades: a systematic review and meta-analysis.
AB - The incidence of patients diagnosed with primary malignant cardiac tumors (PMCTs)
has increased greatly in the past few decades. Whether this rising prevalence is
due to overdiagnosis or an increased malignancy rate of primary cardiac tumors
(PCTs) remains unclear. Therefore, we performed a systematic review and meta
analysis of published retrospective studies to determine whether the malignancy
rate has been increasing over time. Published studies containing relevant data
between 1956 and 2014 were evaluated. Two authors searched for all retrospective
studies that included patients diagnosed with PCT and PMCT. Two other
investigators independently extracted the data, and discrepancies were resolved
by consensus. A random-effects meta-analysis model and cumulative meta-analysis
model were used to evaluate the pooled prevalence and trend of dynamic change in
PCT malignancies. The effects of time, study period and sample size were studied
using a logit-linear regression model with robust error variance and a time
variable. Thirty-eight studies involving 5,586 patients were analyzed. The pooled
prevalence of PMCT among the patients diagnosed with PCT was 9.9% (95% CI, 8.4%
to 11.4%) (I2=70%; P< 0.001), and this prevalence has been stable since around
2003. In the regression model, the malignancy odds ratio remained stable from
1975 onward, and no time effect was observed. Our study confirms that PMCT is
uncommon, and the prevalence of PCT malignancies remained stable in the past few
decades. The clinically observed increase in incidence is unlikely to reflect a
true population-level increase in tumorigenesis. This result strongly suggests
that the observed increase in incidence of PMCT most likely reflects increased
diagnostic detection over time.
PMID- 28489605
TI - Genetic rearrangements result in altered gene expression and novel fusion
transcripts in Sezary syndrome.
AB - Sezary syndrome (SS) is an aggressive, leukemic cutaneous T-cell lymphoma
variant. Molecular pathogenesis of SS is still unclear despite many studies on
genetic alterations, gene expression and epigenetic regulations. Through whole
genome and transcriptome next generation sequencing nine Sezary syndrome patients
were analyzed in terms of copy number variations and rearrangements affecting
gene expression. Recurrent copy number variations were detected within 8q (MYC,
TOX), 17p (TP53, NCOR1), 10q (PTEN, FAS), 2p (DNMT3A), 11q (USP28), 9p (CAAP1),
but no recurrent rearrangements were identified. However, expression of five
genes involved in rearrangements (TMEM244, EHD1, MTMR2, RNF123 and TOX) was
altered in all patients. Fifteen rearrangements detected in Sezary syndrome
patients and SeAx resulted in an expression of new fusion transcripts, nine of
them were in frame (EHD1-CAPN12, TMEM66-BAIAP2, MBD4-PTPRC, PTPRC-CPN2, MYB
MBNL1, TFG-GPR128, MAP4K3-FIGLA, DCP1A-CCL27, MBNL1-KIAA2018) and five resulted
in ectopic expression of fragments of genes not expressed in normal T-cells
(BAIAP2, CPN2, GPR128, CAPN12, FIGLA). Our results not only underscored the
genomic complexity of the Sezary cancer cell genome but also showed an unpreceded
large variety of novel gene rearrangements resulting in fusions transcripts and
ectopically expressed genes.
PMID- 28489606
TI - Pantoprazole blocks the JAK2/STAT3 pathway to alleviate skeletal muscle wasting
in cancer cachexia by inhibiting inflammatory response.
AB - OBJECTIVE: Cancer cachexia is often present in patients with advanced malignant
tumors, and the subsequent body weight reduction results in poor quality of life.
However, there has been no progress in developing effective clinical therapeutic
strategies for skeletal muscle wasting in cancer cachexia. Herein, we explored
the functions of pantoprazole on cancer cachexia skeletal muscle wasting.
METHODS: The mouse colon adenocarcinoma cell line C26 was inoculated in the right
forelimb of male BALB/C mice to establish a cancer cachexia model. The animals
were treated with or without different concentrations of pantoprazole orally, and
the body weight, tumor growth, spontaneous activity, and muscle functions were
determined at various time points. Two weeks later, the levels of serum IL-6 and
TNF-alpha, the mRNA levels of gastrocnemius JAK2 and STAT3, and the expression
levels of p-JAK2, p-STAT3, Fbx32, and MuRF1 were examined with ELISA assay, qRT
PCR assay, and Western blotting, respectively. Further studies were performed to
assess the levels of Fbx32 and MuRF1 expression and morphological changes.
RESULTS: Pantoprazole can alleviate cancer cachexia-induced body weight reduction
and inhibit skeletal muscle wasting in a dose-dependent manner. Our results
indicated that pantoprazole treatment can decrease the levels of serum IL-6 and
TNF-alpha (56.3% and 67.6%, respectively), and inhibit the activation of the
JAK2/STAT3 signaling pathway. Moreover, the expression levels of MuRF1 and Fbx32
were also suppressed after pantoprazole treatment. CONCLUSION: Our findings
suggested that pantoprazole can alleviate cancer cachexia skeletal muscle wasting
by inhibiting the inflammatory response and blocking the JAK2/STAT3 or ubiquitin
proteasome pathway.
PMID- 28489607
TI - Trans-scirpusin A showed antitumor effects via autophagy activation and apoptosis
induction of colorectal cancer cells.
AB - Trans-Scirpusin A (TSA) is a resveratrol oligomer found in Borassus flabellifer
L. We found that TSA inhibited the growth of colorectal cancer Her2/CT26 cells in
vivo in mice. Although some cytotoxic T lymphocytes (CTLs) were induced against
the tumor-associated antigen Her2, TSA treatment did not significantly increase
the level of Her2-specific CTL response compared to that with vehicle treatment.
However, there was a significant increase in the level of TNF-alpha mRNA in tumor
tissue and Her2-specific Ab (antibody) production. More importantly, we found
that TSA overcomes the tumor-associated immunosuppressive microenvironment by
reducing the number of CD25+FoxP3+ regulatory T cells and myeloid-derived
suppressor cells (MDSCs). We detected the induction of autophagy in TSA-treated
Her2/CT26 cells, based on the increased level of the mammalian autophagy protein
LC3 puncta, and increased conversion of LC3-I to LC3-II. Further, TSA induced 5'
AMP-activated protein kinase (p-AMPK) (T172) and inhibited mammalian target of
rapamycin complex 1 (mTORC1) activity as estimated by phosphorylated ribosomal
protein S6 kinase beta-1 (p-p70S6K) levels, thereby suggesting that TSA-mediated
AMPK activation and inhibition of mTORC1 pathway might be associated with
autophagy induction. TSA also induced apoptosis of Her2/CT26 cells, as inferred
by the increased sub-G1 mitotic phases in these cells, Annexin V/PI-double
positive results, and TUNEL-positive cells. Finally, we found that the combined
treatment of mice with docetaxel and TSA successfully inhibited tumor growth to a
greater extent than docetaxel alone. Therefore, we propose the use of TSA for
supplementary anticancer therapy to support anti-neoplastic drugs, such as
docetaxel, by inducing apoptosis in cancer cells and resulting in the induction
of neighborhood anti-cancer immunity.
PMID- 28489608
TI - Simulation study comparing the helmet-chin PET with a cylindrical PET of the same
number of detectors.
AB - There is a growing interest in developing brain PET scanners with high
sensitivity and high spatial resolution for early diagnosis of neurodegenerative
diseases and studies of brain functions. Sensitivity of the PET scanner can be
improved by increasing the solid angle. However, conventional PET scanners are
designed based on a cylindrical geometry, which may not be the most efficient
design for brain imaging in terms of the balance between sensitivity and cost. We
proposed a dedicated brain PET scanner based on a hemispheric shape detector and
a chin detector (referred to as the helmet-chin PET), which is designed to
maximize the solid angle by increasing the number of lines-of-response in the
hemisphere. The parallax error, which PET scanners with a large solid angle tend
to have, can be suppressed by the use of depth-of-interaction detectors. In this
study, we carry out a realistic evaluation of the helmet-chin PET using Monte
Carlo simulation based on the 4-layer GSO detector which consists of a 16 * 16
* 4 array of crystals with dimensions of 2.8 * 2.8 * 7.5 mm3. The purpose of
this simulation is to show the gain in imaging performance of the helmet-chin PET
compared with the cylindrical PET using the same number of detectors in each
configuration. The sensitivity of the helmet-chin PET evaluated with a
cylindrical phantom has a significant increase, especially at the top of the
(field-of-view) FOV. The peak-NECR of the helmet-chin PET is 1.4 times higher
compared to the cylindrical PET. The helmet-chin PET provides relatively low
noise images throughout the FOV compared to the cylindrical PET which exhibits
enhanced noise at the peripheral regions. The results show the helmet-chin PET
can significantly improve the sensitivity and reduce the noise in the
reconstructed images.
PMID- 28489609
TI - Heart rate-based window segmentation improves accuracy of classifying
posttraumatic stress disorder using heart rate variability measures.
AB - OBJECTIVE: Heart rate variability (HRV) characterizes changes in autonomic
nervous system function and varies with posttraumatic stress disorder (PTSD). In
this study we developed a classifier based on heart rate (HR) and HRV measures,
and improved classifier performance using a novel HR-based window segmentation.
APPROACH: Single-channel ECG data were collected from 23 subjects with current
PTSD, and 25 control subjects with no history of PTSD over 24 h. RR intervals
were derived from these data, cleaned, and used to calculate HR and HRV metrics.
These metrics were used as features in a logistic regression classifier.
Performance was assessed via repeated random sub-sampling validation. To reduce
noise and activity-related effects, we calculated features from five non
overlapping ten-minute quiescent segments of RR intervals defined by lowest HR,
as well as random ten-minute segments as a control. MAIN RESULTS: Using a
combination of the four most predictive features derived from quiescent segments
we achieved a median area under the receiver operating curve (AUC) of 0.86 on out
of-sample test set data. This was significantly higher than the AUC using 24 h of
data (0.72) or random segments (0.67). SIGNIFICANCE: These results demonstrate
our segmentation approach improves the classification of PTSD from HR and HRV
measures, and suggest the potential for tracking PTSD illness severity via
objective physiological monitoring. Future studies should prospectively evaluate
if classifier output changes significantly with worsening or effective treatment
of PTSD.
PMID- 28489610
TI - Invasive and noninvasive means of measuring intracranial pressure: a review.
AB - : Measurement of intracranial pressure (ICP) can be invaluable in the management
of critically ill patients. Cerebrospinal fluid is produced by the choroid plexus
in the brain ventricles (a set of communicating chambers), after which it
circulates through the different ventricles and exits into the subarachnoid space
around the brain, where it is reabsorbed into the venous system. If the fluid
does not drain out of the brain or get reabsorbed, the ICP increases, which may
lead to brain damage or death. ICP elevation accompanied by dilatation of the
cerebral ventricles is termed hydrocephalus, whereas ICP elevation accompanied by
normal or small ventricles is termed idiopathic intracranial hypertension.
OBJECTIVE: We performed a comprehensive literature review on how to measure ICP
invasively and noninvasively. APPROACH: This review discusses the advantages and
disadvantages of current invasive and noninvasive approaches. MAIN RESULTS:
Invasive methods remain the most accurate at measuring ICP, but they are prone to
a variety of complications including infection, hemorrhage and neurological
deficits. Ventricular catheters remain the gold standard but also carry the
highest risk of complications, including difficult or incorrect placement. Direct
telemetric intraparenchymal ICP monitoring devices are a good alternative.
Noninvasive methods for measuring and evaluating ICP have been developed and
classified in five broad categories, but have not been reliable enough to use on
a routine basis. These methods include the fluid dynamic, ophthalmic, otic, and
electrophysiologic methods, as well as magnetic resonance imaging, transcranial
Doppler ultrasonography (TCD), cerebral blood flow velocity, near-infrared
spectroscopy, transcranial time-of-flight, spontaneous venous pulsations, venous
ophthalmodynamometry, optical coherence tomography of retina, optic nerve sheath
diameter (ONSD) assessment, pupillometry constriction, sensing tympanic membrane
displacement, analyzing otoacoustic emissions/acoustic measure, transcranial
acoustic signals, visual-evoked potentials, electroencephalography, skull
vibrations, brain tissue resonance and the jugular vein. SIGNIFICANCE: This
review provides a current perspective of invasive and noninvasive ICP
measurements, along with a sense of their relative strengths, drawbacks and areas
for further improvement. At present, none of the noninvasive methods demonstrates
sufficient accuracy and ease of use while allowing continuous monitoring in
routine clinical use. However, they provide a realizable ICP measurement in
specific patients especially when invasive monitoring is contraindicated or
unavailable. Among all noninvasive ICP measurement methods, ONSD and TCD are
attractive and may be useful in selected settings though they cannot be used as
invasive ICP measurement substitutes. For a sufficiently accurate and universal
continuous ICP monitoring method/device, future research and developments are
needed to integrate further refinements of the existing methods, combine
telemetric sensors and/or technologies, and validate large numbers of clinical
studies on relevant patient populations.
PMID- 28489611
TI - FDG PET/CT in Aortic Valve Bioprosthesis Infection.
AB - A 62-year-old man presented with persistent fever, weakness, and retrosternal
pain 3 years after aortic valve bioprosthesis (AVR). His white blood cell count
was 11,000/MUL and C-reactive protein was 13.6 mg/dL. Consecutive blood cultures
isolated Staphylococcus epidermidis and capitis. Transesophageal echocardiography
demonstrated small aortic valve prosthesis vegetation. F-FDG PET/CT revealed
prominent AVR activity, SUVmax = 12.2. He was treated with daptomycin, meropenem,
and gentamicin for 1 month and followed by daptomycin and carbapenem for 3
months. Follow-up F-FDG PET/CT at 6 months demonstrated complete clearing of AVR
activity associated with full asymptomatic recovery.
PMID- 28489612
TI - Correlation between ambulatory blood pressure variability and vasodilator
function in middle-aged normotensive individuals.
AB - OBJECTIVE: The aim of this study was to investigate the association between
ambulatory blood pressure variability and vasodilator function in a cohort of
normotensive middle-aged individuals. PARTICIPANTS AND METHODS: This was a cross
sectional study of 285 randomly selected 40-59-year-old normotensive participants
who underwent 24-h ambulatory blood pressure monitoring and brachial artery
ultrasound assessment. Systolic and diastolic blood pressure variability (BPV) of
24-h, daytime, and night-time were calculated using the coefficients of variation
(CV) and the average real variability (ARV) index. Brachial arterial endothelium
dependent vasodilation (EDD) was assessed in response to increased flow and
endothelium-independent vasodilation (EID) was assessed in response to
nitroglycerin. Relationships were explored using univariate and multivariate
linear regression. RESULTS: The EDD were negatively associated with the CV of 24
h systolic blood pressure (SBP), the ARV of 24-h SBP, and diastolic blood
pressure (DBP) in univariate analysis. However, the CV and ARV of 24-h SBP
remained associated independently with % EDD in multivariate analysis. In
addition, the mean levels of 24-h SBP and DBP, the CV of 24-h SBP and DBP, the
ARV of 24-h SBP and DBP, the CV of daytime SBP, and the ARV of daytime DBP were
all associated with % EID. However, in a multiple linear regression model,
adjusting for covariates, only the CV and ARV of 24-h SBP, and the ARV of 24-h
DBP were correlated negatively but weakly with % EID. CONCLUSION: Our results
indicated that a higher 24-h BPV was associated independently with decreased
endothelial-dependent and endothelial-independent vasodilator functions in a
middle-aged normotensive population. Although 24-h BPV was associated with
vasodilator function, relationships were attenuated after adjusting for
covariates.
PMID- 28489613
TI - The effect of back and feet support on oscillometric blood pressure measurements.
AB - BACKGROUND/OBJECTIVE: Recommendations to support the back and feet during blood
pressure (BP) measurement are not always followed in clinical practice. Our
objective was to determine to what extent back and feet support affects mean
oscillometric BP measurements. PARTICIPANTS AND METHODS: Eighty-five consecutive,
consenting participants 18 years or older with systolic BP readings 80-220 mmHg
and diastolic BP readings 50-120 mmHg and arm circumferences of 25-43 cm were
recruited. BP was measured using an Omron HEM 907 oscillometric device. Back and
feet support were examined independently. First, while the feet were supported,
two sets of three BP readings were taken in random order: one with the back
supported and one with the back unsupported. Next, with the back supported, two
sets of three BP readings were taken in random order: one with the feet dangling
and one with feet supported. RESULTS: The mean age of the participants was 52.0+/
20.7 years and the mean arm circumference was 31.0+/-3.2 cm; 62% were women and
49% had hypertension. The mean BP levels with the back unsupported were slightly
higher than those with the back supported (119.8+/-15.5/69.9+/-8.9 vs. 119.2+/
16.4/68.2+/-8.8 mmHg; difference of 0.7+/-4.9/1.8+/-3.0; P=0.21 for systolic and
<0.0001 for diastolic comparisons). The mean BP levels with feet dangling were
slightly lower than with feet supported (120.3+/-16.3/72.6+/-8.9 vs. 121.2+/
16.1/72.9+/-8.6 mmHg; difference of -0.9+/-4.1/-0.3+/-2.8; P=0.04 for systolic
and <0.36 for diastolic comparisons). Systolic BP differences were greater than
or equal to 5 mmHg in 34% (back phase) and 23% (feet phase) of the participants.
CONCLUSION: Provision of back and feet support has a small effect on the mean
oscillometric BP. The magnitude of effect is greatest on diastolic BP when the
back is unsupported.
PMID- 28489614
TI - Validation of Innovative Techniques for Monitoring Nociception during General
Anesthesia: A Clinical Study Using Tetanic and Intracutaneous Electrical
Stimulation.
AB - BACKGROUND: This study compares the analgesic indices Analgesia Nociception Index
(heart rate variability), Surgical Pleth Index (photoplethysmography), and
pupillary dilatation, to heart rate, mean arterial pressure, and bispectral
index, with regard to diagnostic accuracy and prediction probability for
nociceptive response. The primary endpoint was the correlation between Delta
values and the remifentanil dose administered. METHODS: We anesthetized 38
patients with propofol and increasing doses of remifentanil and applied
standardized tetanic and intracutaneous electrical painful stimulations on each
analgesic level. Baseline and Delta values of the Analgesia Nociception Index,
the Surgical Pleth Index, pupillary dilatation, heart rate, mean arterial
pressure, and bispectral index and their relation to remifentanil doses were
analyzed by receiver operating characteristic curves, prediction probability
(PK), and mixed-model analysis. RESULTS: Under propofol sedation, sensitivity and
specificity of the Analgesia Nociception Index (PK = 0.98), the Surgical Pleth
Index (PK = 0.87), and pupillary dilatation (PK = 0.98) for detecting both
painful stimulations were high compared to heart rate (PK = 0.74), mean arterial
pressure (PK = 0.75), and bispectral index (PK = 0.55). Baseline values had
limited prediction probability toward the nociceptive response (Analgesia
Nociception Index: PK = 0.7; Surgical Pleth Index: PK = 0.63; pupillary
dilatation: PK = 0.67; and bispectral index: PK = 0.67). The remifentanil dose
had an effect (P < 0.001) on all parameters except for bispectral index (P =
0.216). CONCLUSIONS: The Analgesia Nociception Index, the Surgical Pleth Index,
and pupillary dilatation are superior in detecting painful stimulations compared
to heart rate and mean arterial pressure but had limited predictive value. These
effects are attenuated by increasing dosages of remifentanil. Our data confirm
that bispectral index is not a marker of analgesia.
PMID- 28489615
TI - Report of two cases of acute cardiac adverse events in patients with colorectal
carcinoma receiving oral capecitabine.
AB - Capecitabine is an oral fluoropyrimidine chemotherapeutic agent, which, after
oral administration, is metabolized to its active cytotoxic compound: 5
fluorouracil (5-FU). Cardiotoxicity is a recognized side effect of 5-FU, a
closely related fluorinated pyrimidine antagonist. In the present report, we
report on two patients who were admitted to our department after being treated
with oral capecitabine for colorectal carcinoma and developed symptoms and signs
of acute myocardial infarction that resolved after appropriate treatment and
monitoring. The above two cases are discussed in the context of fluoropyrimidine,
5-FU, and capecitabine-induced cardiotoxicity; in addition, a detailed literature
review of relevant cases and patient series reports is presented.
PMID- 28489617
TI - Best Practices for Increasing Reading Compliance in Undergraduate Medical
Education.
PMID- 28489616
TI - Complete response to anti-PD-1 nivolumab in massive skin metastasis from
melanoma: efficacy and tolerability in an elderly patient.
AB - The advent of immune checkpoint inhibitors anti-PD-1/PD-L1 has delivered new and
effective treatment options with proven clinical benefits for patients affected
by metastatic melanoma. The 30-40% of treated patients experience an objective
tumour regression, with a significantly prolonged survival and an improved
quality of life. Here, we report a case of a 75-year-old Caucasian woman affected
by a massive cutaneous metastasis from a BRAF wild-type melanoma who experienced
multiple relapses after surgery and repeated electrochemotherapy treatments. A
poor response was observed after systemic therapy with ipilimumab, whereas a
marked reduction in the lesion size was obtained during the treatment with
nivolumab, with an objectively complete response after 6 months. Therapy was well
tolerated, without immune-related side effects. During treatment, LDH levels
decreased up to the standard values. Our experience confirms the good efficacy
and the safety of anti-PD-1 nivolumab for the treatment of relapsed or refractory
massive skin lesions, also in elderly patients.
PMID- 28489618
TI - Core Competencies or a Competent Core? A Scoping Review and Realist Synthesis of
Invasive Bedside Procedural Skills Training in Internal Medicine.
AB - PURPOSE: Invasive bedside procedures are core competencies for internal medicine,
yet no formal training guidelines exist. The authors conducted a scoping review
and realist synthesis to characterize current training for lumbar puncture,
arthrocentesis, paracentesis, thoracentesis, and central venous catheterization.
They aimed to collate how educators justify using specific interventions,
establish which interventions have the best evidence, and offer directions for
future research and training. METHOD: The authors systematically searched
Medline, Embase, the Cochrane Library, and ERIC through April 2015. Studies were
screened in three phases; all reviews were performed independently and in
duplicate. The authors extracted information on learner and patient demographics,
study design and methodological quality, and details of training interventions
and measured outcomes. A three-step realist synthesis was performed to synthesize
findings on each study's context, mechanism, and outcome, and to identify a
foundational training model. RESULTS: From an initial 6,671 studies, 149 studies
were further reduced to 67 (45%) reporting sufficient information for realist
synthesis. Analysis yielded four types of procedural skills training
interventions. There was relative consistency across contexts and significant
differences in mechanisms and outcomes across the four intervention types. The
medical procedural service was identified as an adaptable foundational training
model. CONCLUSIONS: The observed heterogeneity in procedural skills training
implies that programs are not consistently developing residents who are competent
in core procedures. The findings suggest that researchers in education and
quality improvement will need to collaborate to design training that develops a
"competent core" of proceduralists using simulation and clinical rotations.
PMID- 28489619
TI - Pediatric Resident Academic Projects While on Global Health Electives: Ten Years
of Experience at the University of Minnesota.
AB - PURPOSE: Many residency programs require residents to complete an academic
project as part of a global health (GH) elective. However, there has been little
description of the range of projects residents have pursued during GH electives
or the extent to which these projects are consistent with proposed best
practices. METHOD: The authors conducted a document review of 67 written
summaries or copies of presentations of academic projects (hereafter, summaries)
completed by pediatric and medicine-pediatric residents at the University of
Minnesota while on GH electives from 2005 to 2015. Two authors independently
coded each summary for the type of project completed; when the project idea was
generated; explicit mention of a mentor from the home institution, host
institution, or both; whether a needs assessment was conducted; and whether there
were plans for sustainability. RESULTS: Most of the 67 projects were categorized
into one of three project types: quality/process improvement (28 [42%]),
education (18 [27%]), or clinical research (14 [21%]). Most summaries explicitly
mentioned a mentor (45 [67%]), reported conducting a needs assessment (38 [57%]),
and indicated sustainability plans (45 [67%]). Of the 42 summaries that indicated
the timing of idea generation, 30 (71%) indicated the idea was developed after
arriving at the host site. CONCLUSIONS: Residents undertook a wide range of
academic projects during GH electives, most commonly quality/process improvement
and education projects. The projects were largely aligned with best practices,
with most summaries indicating the resident worked with a mentor, conducted a
needs assessment, and made plans for sustainability.
PMID- 28489620
TI - Adult desmoid tumors: biology, management and ongoing trials.
AB - PURPOSE OF REVIEW: To summarize the current knowledge about the biology and
clinical management of adult desmoid tumors. RECENT FINDINGS: In the past decade,
we have learned that desmoid tumors are driven by alterations of the Wnt/APC/beta
catenin pathway, sporadic desmoid tumors are associated with somatic mutations of
CTNNB1, and germline mutations of APC and somatic mutations of CTNNB1 are
probably mutually exclusive. One-third of desmoid tumors are misdiagnosed; a
second pathological opinion is therefore of major importance for desmoid tumor.
Surgery is no longer regarded as the cornerstone of desmoid tumors; several
retrospective studies have demonstrated the safety of a 'wait and see' policy in
sporadic abdominal wall desmoid tumor. Desmoid tumors is no longer regarded as an
absolute contraindication for pregnancy. At least two new investigational drugs
targeting the Wnt/APC/beta-catenin pathway are currently being developed.
SUMMARY: The management of desmoid tumors requires multidisciplinary expertise by
an experienced team. We must fully understand the physiopathology of the disease
(factors influencing the natural history of the disease) and learn how to avoid
desmoid tumors occurrence in patients with APC germline mutations, identify
reliable prognostic/predictive factors and better assess the efficacy of systemic
treatment.
PMID- 28489622
TI - Periorbital Papular Amyloidosis.
PMID- 28489621
TI - Own and partner pain intensity in older couples: longitudinal effects on
depressive symptoms.
AB - Chronic pain has been linked to depression among individuals and their partners.
Yet, little is known about long-term mutual influences between pain intensity and
depressive symptoms within couples as they age. Using a nationally representative
U.S. sample of wives and husbands aged 50 and older (mean = 64.53, SD = 7.86),
this study explored the links between own and partner pain intensity and
depressive symptoms across an 8-year period. A total of 963 heterosexual married
couples drawn from the Health and Retirement Study completed interviews
biennially from 2006 to 2014. Dyadic growth curve models examined mutual
associations within couples and controlled for sociodemographic characteristics,
length of marriage, and marital quality, along with self-rated health, number of
chronic health conditions, and functional disability. For wives and husbands,
their own greater baseline pain intensity was significantly linked to their own
higher levels of depressive symptoms. Unexpectedly, wives with greater baseline
pain intensity reported decreases in their depressive symptoms over time. There
were also partner effects such that husbands' greater pain intensity at baseline
was associated with increases in wives' depressive symptoms over time. Findings
highlight the importance of considering both individual and spousal associations
between pain intensity and depressive symptoms in later life. Understanding how
individual and couple processes unfold may yield critical insights for the
development of intervention and prevention efforts to maintain mental health
among older chronic pain patients and their spouses.
PMID- 28489623
TI - Retinal and Choroidal Detachment in Antineutrophil Cytoplasmic Antibody
Associated Scleritis and Retinal Vasculitis Mimicking Choroidal Tumor.
PMID- 28489624
TI - Defining Quality of Rheumatologic Care: Mexico.
AB - We present an overview of rheumatology practices in Mexico, describing the
national health care system as segmented and fragmentary, with a population
separated into 3 main categories, according to employment-based coverage and
income level: (1) private sector, (2) Social Security System, and (3) public
insurance subsector.The rheumatology practice in the public and private sectors
are described. We estimate that between 85%-90% of Mexican rheumatologists have a
mixed (public and private)-type practice. Payments to rheumatologists are not
currently affected by quality and value metrics, with low penetrance of
electronic health records. Recent changes and challenges to health insurance
coverage are illustrated.
PMID- 28489625
TI - The Disease of the Italian Poet Giacomo Leopardi (1798-1837): A Case of Juvenile
Ankylosing Spondylitis in the 19th Century?
AB - Some authors sustained that the pessimistic thought of the Italian writer and
philosopher Giacomo Leopardi (1798-1837) may be attributed to his unhappy life,
characterized by several health problems. His philosophical theories appear as
the result of depressive and melancholic state, related to his precarious health
conditions, so limiting their intrinsic values. Several authors formulated
various hypotheses on the diseases that Leopardi suffered from and postulated
different theories on the cause of his early death. This article assumed that
Leopardi may have been affected by juvenile ankylosing spondylitis, conditioning
spinal deformities, relapsing-remitting uveitis, urinary tract and bowel tract
problems, and acute arthritis. Chest deformity, as a complication of juvenile
ankylosing spondylitis, may have caused progressive cardiorespiratory failure,
worsened by recurrent bronchial and pulmonary complications, until his death
caused by acute right ventricular heart failure. The acknowledgment of a physical
cause of Leopardi's disease contributes to reevaluate his "cosmic pessimism" as
an original expression of his thought, so leading a general revaluation of the
figure of one of the most important European thinkers of the 19th century.
PMID- 28489627
TI - Radial Head Ingrowth Anatomic Implant Versus Smooth Stem Monoblock Implant in
Acute Terrible Triad Injury: A Prospective Comparative Study.
AB - OBJECTIVE: This study aimed to compare clinical outcomes and radiographic
findings between patients who received 2 different implants (smooth-stemmed
modular implant or an anatomic press-fit implant) on patients with acute terrible
triad injuries. DESIGN: Prospective cohort. SETTING: Level II Trauma center,
University hospital. PATIENTS/PARTICIPANTS: Thirty-four patients with an isolated
terrible triad injury were divided into 2 study groups (n = 17 each) with
different sets of radial head implants and followed for 2 years. A total of 14
patients in each group (n = 28) completed the study. INTERVENTION: Group 1
received a smooth-stemmed round modular monopolar implant. Group 2 received an in
growth modular monopolar press-fit anatomic implant. MAIN OUTCOME MEASUREMENTS:
Clinical outcomes were evaluated using the Visual Analog Scale, Mayo Index, and
Disabilities of the Arm, Shoulder, and Hand (DASH) survey. Radiographs were
evaluated for ectopic bone formation and loosening. RESULTS: No difference in
clinical outcome when comparing range of motion and functionally scores between
groups. Ectopic bone formation occurred equally with implants. Bone formation at
the proximal radius under the implant occurred more in group 1 (85.7%), (P =
0.046). Five press-fit stems had radiolucent lines at 2-year follow-up. Two were
removed because of symptomatic loosening. CONCLUSIONS: Short-term outcomes for
both implants showed to be equally effective treatment options. The in vitro
biomechanical advantages of anatomic implants do not translate into short-term
improved outcomes. Symptomatic aseptic loosening in anatomic implants is common.
Bone formation at the proximal radial neck was observed more with smooth-stemmed
implants; further studies should assess this findings and clinical implication.
LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a
complete description of levels of evidence.
PMID- 28489628
TI - Lengthening of newly formed humerus after autologous fibula graft transplantation
following intercalary tumor resection.
AB - Secondary limb lengthening after intercalary bone resection in pediatric patients
is still challenging. After the resection, a free fibula autograft can be used to
reconstruct the osseous gap. However, in particular in young pediatric patients,
insufficient growth of the epiphyseal plate after transplantation may lead to a
significant limb-length discrepancy (LLD). In this case, the autograft was used
for limb lengthening. We report on the lengthening of a humerus regenerate after
fibula autograft transplantation into a humeral defect in a pediatric/young
adolescent patient. Because of LLD, she underwent callus distraction of the
humerus regenerate after transplantation of a fibula autograft using a unilateral
external fixator device. An 18-year-old female patient with status
postintercalary proliferating chondroma resection (at the age of 7 years)
required treatment for correction of a 13 cm humerus shortening. She reported no
pain, had no functional limitations, and had a full range of motion of the
shoulder and elbow joint. She complained about her short humerus and overall body
scheme. A unilateral external fixator device for callus distraction was applied
to the transplanted humerus regenerate after free fibula autograft
transplantation. Bone lengthening was performed by distraction (2*0.5 mm/day).
After 62 days and a lengthening of 6 cm in total, bone distraction was stopped
mainly to avoid any complication. At this time, there was no limitation in the
range of motion. No nerve palsy or other problems occurred at any time of the
distraction. In pediatric patients, the transplantation of a fibula autograft is
a well-established option to bridge an osseous gap after intercalary bone
resection. This case report shows that even the humerus regenerate after fibula
autograft transplantation has excellent potential for callotasis and bone
remodeling and therefore bone lengthening in patients with LLD is an option even
after transplantation of an autograft. This method provides a new therapeutic
option for patients with LLD after fibula transplantation.
PMID- 28489629
TI - Modulation of Isometric Quadriceps Strength in Soccer Players With Transcranial
Direct Current Stimulation: A Crossover Study.
AB - Vargas, VZ, Baptista, AF, Pereira, GOC, Pochini, AC, Ejnisman, B, Santos, MB,
Joao, SMA, and Hazime, FA. Modulation of isometric quadriceps strength in soccer
players with transcranial direct current stimulation: a crossover study. J
Strength Cond Res 32(5): 1336-1341, 2018-The aim of this study was to evaluate
the effect of transcranial direct current stimulation (tDCS) on the maximum
isometric muscle contraction (MVIC) of the knee extensors in soccer players at
the preprofessional level. Twenty female soccer players aged 15-17 years (mean =
16.1; SD = 0.9) with 5.2 +/- 2.6 years of training were randomly divided into 2
groups to receive either active or sham tDCS in a single session (2 mA; 0.057
mA.cm). The MVIC of the knee extensors was evaluated in both lower limbs by
manual dynamometry in 5 sets of contractions divided into 4 blocks: (a)
prestimulation, (b) during tDCS, (c) 30 minutes after tDCS, and (d) 60 minutes
after tDCS. After an interval of 7 days, the groups were evaluated again, and the
type of initial stimulation was inverted between participants. The MVIC of the
knee extensors increased significantly during active tDCS (dominant limb (DL) =
0.4; IC = 0.1-0.8 N.Kg), 30 minutes after active tDCS (DL = 0.9; IC 0.4-1.4
N.Kg), and 60 minutes after active tDCS (DL = 1.0; IC 0.3-1.6 N.Kg) but not for
sham tDCS. Our conclusion was that tDCS temporarily increases isometric
quadriceps strength in adolescent female soccer players, which may be useful for
both strength training and rehabilitation.
PMID- 28489630
TI - Effects of Incisional Negative-Pressure Wound Therapy on Primary Closed Defects
after Superficial Circumflex Iliac Artery Perforator Flap Harvest: Randomized
Controlled Study.
PMID- 28489631
TI - Looking Beyond the Knife: Establishing a Framework for Micropigmentation
following Breast Reconstruction.
PMID- 28489632
TI - Comparison of Preoperative and Postoperative Lymphatic Function is Essential to
Understand the Changes in Lymphatic Function.
PMID- 28489633
TI - Reply: Comparison of Preoperative and Postoperative Lymphatic Function is
Essential to Understand the Changes in Lymphatic Function.
PMID- 28489634
TI - Reply: Effects of Negative-Pressure Wound Therapy on Primary Closed Defects after
Superficial Circumflex Iliac Artery Perforator Flap Harvest: Randomized
Controlled Study.
PMID- 28489635
TI - Trends in sex differences in clinical characteristics, treatment strategies, and
mortality in patients with ST-elevation myocardial infarction in Poland from 2005
to 2011.
AB - INTRODUCTION: During the last decade, there has been an increased awareness of
sex differences in the clinical characteristics, management, and mortality in
myocardial infarction. Many previous studies have found that women with ST
elevation myocardial infarction (STEMI) have a poorer baseline risk profile, are
less intensively treated, and have worse outcomes. OBJECTIVE: To evaluate whether
sex disparities in STEMI have changed in recent years. METHODS: This is a
retrospective analysis of data on 111 148 STEMI patients enrolled in the Polish
Registry of Acute Coronary Syndromes between 2005 and 2011. Temporal trends in
the clinical presentation, treatment strategies, and mortality rates between men
and women are compared. RESULTS: Throughout the study, women were, on average,
older than men, and more frequently presented with hypertension, diabetes, or
obesity. These differences showed a tendency for narrowing. The percentage of
smokers increased in both sexes. Despite a reduction in prehospital delays, they
remained longer in women. Sex differences in prehospital cardiac arrest and
cardiogenic shock at admission disappeared. In 2011, women were still less likely
to undergo coronary angiography with subsequent revascularization, but it was
mainly driven by patients older than 70 years of age who also had a higher in
hospital mortality. Despite the greater relative risk reductions, the crude
mortality rates remained significantly higher in women. Female sex was not an
independent predictor of mortality. CONCLUSION: Sex differences in STEMI patients
were narrowing from 2005 to 2011 in Poland. However, more attention needs to be
focused on increasing smoking prevalence, the longer times from symptoms onset to
hospital admission in women and the lower frequencies of the use of an invasive
treatment strategy in older women, and their worse in-hospital outcomes.
PMID- 28489636
TI - A selective approach to coronary revascularization among patients undergoing
transcatheter aortic valve replacement.
PMID- 28489637
TI - Pilot Study Comparing Closed Versus Open Tracheal Suctioning in Postoperative
Neonates and Infants With Complex Congenital Heart Disease.
AB - OBJECTIVES: To determine the hemodynamic effect of tracheal suction method in the
first 36 hours after high-risk infant heart surgery on the PICU and to compare
open and closed suctioning techniques. DESIGN: Pilot randomized crossover study.
SETTING: Single PICU in United Kingdom. PARTICIPANTS: Infants undergoing surgical
palliation with Norwood Sano, modified Blalock-Taussig shunt, or pulmonary artery
banding in the first 36 hours postoperatively. INTERVENTIONS: Infants were
randomized to receive open or closed (in-line) tracheal suctioning either for
their first or second study tracheal suction in the first 36 hours
postoperatively. MEASUREMENTS AND MAIN RESULTS: Twenty-four infants were enrolled
over 18 months, 11 after modified Blalock-Taussig shunt, seven after Norwood
Sano, and six after pulmonary artery banding. Thirteen patients received the open
suction method first followed by the closed suction method second, and 11
patients received the closed suction method first followed by the open suction
method second in the first 36 hours after their surgery. There were statistically
significant larger changes in heart rate (p = 0.002), systolic blood pressure (p
= 0.022), diastolic blood pressure (p = 0.009), mean blood pressure (p = 0.007),
and arterial saturation (p = 0.040) using the open suction method, compared with
closed suctioning, although none were clinically significant (defined as
requiring any intervention). CONCLUSIONS: There were no clinically significant
differences between closed and open tracheal suction methods; however, there were
statistically significant greater changes in some hemodynamic variables with open
tracheal suctioning, suggesting that closed technique may be safer in children
with more precarious physiology.
PMID- 28489638
TI - Current Status of Cardiovascular Anesthesia in China.
AB - High quality and safe cardiac anesthesia is a prerequisite for success in cardiac
care. Cardiac surgery has developed rapidly over recent years in China. Because
of language barriers, the current status of cardiac anesthesia in China is not
well known to Western countries. To assess practice patterns, volume, workforce,
and training requirements of Chinese cardiovascular anesthesiologists, we
surveyed 92 major cardiovascular centers in China regarding their anesthesia
practice, monitoring techniques, resources, staffing, and work hours. We aim to
provide a review of the history, new developments, and a current cross section of
cardiac anesthesia practice patterns in China. The goal is to allow Western
readers to understand the unique achievements and challenges in Chinese
cardiovascular anesthesiology, thus promoting further communications with Chinese
cardiovascular anesthesiologists.
PMID- 28489639
TI - Evaluation of Analgesia, Tolerance, and the Mechanism of Action of Morphine-6-O
Sulfate Across Multiple Pain Modalities in Sprague-Dawley Rats.
AB - BACKGROUND: Morphine-6-O-sulfate (M6S) is a mixed MU/delta-opioid receptor (OR)
agonist and potential alternative to morphine for treatment of chronic multimodal
pain. METHODS: To provide more support for this hypothesis, the antinociceptive
effects of M6S and morphine were compared in tests that access a range of pain
modalities, including hot plate threshold (HPT), pinprick sensitivity threshold
(PST) and paw pressure threshold tests. RESULTS: Acutely, M6S was 2- to 3-fold
more potent than morphine in HPT and PST tests, specifically, derived from best
fit analysis of dose-response relationships of morphine/M6S half-effective dose
(ED50) ratios (lower, upper 95% confidence interval [CI]) were 2.8 (2.0-5.8) in
HPT and 2.2 (2.1, 2.4) in PST tests. No differences in analgesic drug potencies
were detected in the PPT test (morphine/M6S ED50 ratio 1.2 (95% CI, 0.8-1.4).
After 7 to 9 days of chronic treatment, tolerance developed to the
antinociceptive effects of morphine, but not to M6S, in all 3 pain tests.
Morphine-tolerant rats were not crosstolerant to M6S. The antinociceptive effects
of M6S were not sensitive to kappa-OR antagonists. However, the delta-OR
antagonist, naltrindole, blocked M6S-induced antinociception by 55% +/- 4% (95%
CI, 39-75) in the HPT test, 94% +/- 4% (95% CI, 84-105) in the PST test, and 5%
+/- 17% (95% CI, -47 to 59) or 51% +/- 14% (95% CI, 14-84; 6 rats per each group)
in the paw pressure threshold test when examined acutely or after 7 days of
chronic treatment, respectively. CONCLUSIONS: Activity via delta-ORs thus appears
to be an important determinant of M6S action. M6S also exhibited favorable
antinociceptive and tolerance profiles compared with morphine in 3 different
antinociceptive assays, indicating that M6S may serve as a useful alternative for
rotation in morphine-tolerant subjects.
PMID- 28489640
TI - Little Black Boxes: Noncardiac Implantable Electronic Medical Devices and Their
Anesthetic and Surgical Implications.
AB - Implanted electronic medical devices. or stimulators such as pacemakers and nerve
stimulators have grown enormously in diversity and complexity over recent
decades. The function and potential interaction of these devices with the
perioperative environment is of increasing concern for anesthesiologists and
surgeons. Because of the innate electromagnetic environment of the hospital
(operating room, gastrointestinal procedure suite, and imaging suite), implanted
device malfunction, reprogramming, or destruction may occur and cause physical
harm (including nerve injury, blindness, deafness, burn, stroke, paralysis, or
coma) to the patient. It is critical for the anesthesiologist and surgeon to be
aware of the function and interaction of implanted devices, both with other
implanted devices and procedures (such as magnetic resonance imaging and
cardioversion) in the hospital environment. Because of these interactions, it is
imperative that proper device function is assessed when the surgical procedure is
complete. This review article will discuss these important issues for 12
different types of "little black boxes," or noncardiac implantable electronic
medical devices.
PMID- 28489642
TI - Pupillary Reflex for Evaluation of Thoracic Paravertebral Block: A Prospective
Observational Feasibility Study.
AB - BACKGROUND: Although thoracic paravertebral block (TPVB) is recommended in major
breast surgery, there is no gold standard to assess the success of TPVB.
Pupillary dilation reflex (PDR) is the variation of the pupillary diameter after
a noxious stimulus. The objective was to evaluate the feasibility of recording
the PDR to assess analgesia in an anesthetized thoracic dermatome after TPVB.
METHODS: This prospective, observational, single-center study included 32
patients requiring breast surgery under general anesthesia and TPVB. TPVB was
performed before surgery under ultrasound guidance with 20 mL of 0.75%
ropivacaine. At the end of the surgery, remifentanil was stopped and the PDR was
recorded after a 5-second tetanic stimulation (60 mA, 100 Hz) applied to the
anterior chest wall. The PDR was defined as the maximal increase in pupil
diameter after a standardized noxious stimulus, expressed as a percentage of the
initial pupil diameter. The PDR was recorded twice in the same eye for each
patient after a stimulus on both the TPVB and the control sides. Postoperative
pain scores were recorded in a postanesthesia care unit. The primary outcome was
the difference between the PDR on the TPVB and the control sides. RESULTS: The
median (interquartile range) PDR was 9% (4%-13%) on the TPVB side and 41% (27%
66%) on the control side. There was a significant difference in the PDR between
the TPVB and the control sides with a Hodges-Lehmann estimate of absolute
difference of 37% points (95% confidence interval, 25-52, P < .001). Median
postoperative pain scores (interquartile range) in the postanesthesia care unit
were 1 (0-3) at rest and 1 (0-3) during mobilization, respectively. There was a
linear correlation between maximal postoperative pain scores and the PDR on the
TPVB side with a Pearson's correlation coefficient r = 0.40 (95% confidence
interval, 0.06-0.66, P = .02). No correlation was found between the number of
blocked dermatomes and maximal postoperative pain scores (P = .06) or between the
number of blocked dermatomes and the PDR on the TPVB side (P = .15). CONCLUSIONS:
This proof-of-concept trial suggests that the effect of TPVB could be monitored
by measuring the PDR after anterior chest wall stimulation in the dermatome of
interest.
PMID- 28489641
TI - Differences in Blood Pressure in Infants After General Anesthesia Compared to
Awake Regional Anesthesia (GAS Study-A Prospective Randomized Trial).
AB - BACKGROUND: The General Anesthesia compared to Spinal anesthesia (GAS) study is a
prospective randomized, controlled, multisite, trial designed to assess the
influence of general anesthesia (GA) on neurodevelopment at 5 years of age. A
secondary aim obtained from the blood pressure data of the GAS trial is to
compare rates of intraoperative hypotension after anesthesia and to identify risk
factors for intraoperative hypotension. METHODS: A total of 722 infants <=60
weeks postmenstrual age undergoing inguinal herniorrhaphy were randomized to
either bupivacaine regional anesthesia (RA) or sevoflurane GA. Exclusion criteria
included risk factors for adverse neurodevelopmental outcome and infants born at
<26 weeks of gestation. Moderate hypotension was defined as mean arterial
pressure measurement of <35 mm Hg. Any hypotension was defined as mean arterial
pressure of <45 mm Hg. Epochs were defined as 5-minute measurement periods. The
primary outcome was any measured hypotension <35 mm Hg from start of anesthesia
to leaving the operating room. This analysis is reported primarily as intention
to treat (ITT) and secondarily as per protocol. RESULTS: The relative risk of GA
compared with RA predicting any measured hypotension of <35 mm Hg from the start
of anesthesia to leaving the operating room was 2.8 (confidence interval [CI],
2.0-4.1; P < .001) by ITT analysis and 4.5 (CI, 2.7-7.4, P < .001) as per
protocol analysis. In the GA group, 87% and 49%, and in the RA group, 41% and
16%, exhibited any or moderate hypotension by ITT, respectively. In multivariable
modeling, group assignment (GA versus RA), weight at the time of surgery, and
minimal intraoperative temperature were risk factors for hypotension.
Interventions for hypotension occurred more commonly in the GA group compared
with the RA group (relative risk, 2.8, 95% CI, 1.7-4.4 by ITT). CONCLUSIONS: RA
reduces the incidence of hypotension and the chance of intervention to treat it
compared with sevoflurane anesthesia in young infants undergoing inguinal hernia
repair.
PMID- 28489643
TI - Factors Influencing Quality of Pain Management in a Physician Staffed Helicopter
Emergency Medical Service.
AB - BACKGROUND: Pain is frequently encountered in the prehospital setting and needs
to be treated quickly and sufficiently. However, incidences of insufficient
analgesia after prehospital treatment by emergency medical services are reported
to be as high as 43%. The purpose of this analysis was to identify modifiable
factors in a specific emergency patient cohort that influence the pain suffered
by patients when admitted to the hospital. METHODS: For that purpose, this
retrospective observational study included all patients with significant pain
treated by a Swiss physician-staffed helicopter emergency service between April
and October 2011 with the following characteristics to limit selection bias: Age
> 15 years, numerical rating scale (NRS) for pain documented at the scene and at
hospital admission, NRS > 3 at the scene, initial Glasgow coma scale > 12, and
National Advisory Committee for Aeronautics score < VI. Univariate and
multivariable logistic regression analyses were performed to evaluate patient and
mission characteristics of helicopter emergency service associated with
insufficient pain management. RESULTS: A total of 778 patients were included in
the analysis. Insufficient pain management (NRS > 3 at hospital admission) was
identified in 298 patients (38%). Factors associated with insufficient pain
management were higher National Advisory Committee for Aeronautics scores, high
NRS at the scene, nontrauma patients, no analgesic administration, and treatment
by a female physician. In 16% (128 patients), despite ongoing pain, no analgesics
were administered. Factors associated with this untreated persisting pain were
short time at the scene (below 10 minutes), secondary missions of helicopter
emergency service, moderate pain at the scene, and nontrauma patients. Sufficient
management of severe pain is significantly better if ketamine is combined with an
opioid (65%), compared to a ketamine or opioid monotherapy (46%, P = .007).
CONCLUSIONS: In the studied specific Swiss cohort, nontrauma patients, patients
on secondary missions, patients treated only for a short time at the scene before
transport, patients who receive no analgesic, and treatment by a female physician
may be risk factors for insufficient pain management. Patients suffering pain at
the scene (NRS > 3) should receive an analgesic whenever possible. Patients with
severe pain at the scene (NRS >= 8) may benefit from the combination of ketamine
with an opioid. The finding about sex differences concerning analgesic
administration is intriguing and possibly worthy of further study.
PMID- 28489644
TI - An Open-Source Ultrasound Software for Diagnosis of Fistula Maturation.
AB - Vascular access is essential for hemodialysis patients. The mature native
arteriovenous fistula has been the preferred vascular access for hemodialysis,
because it has greater longevity than synthetic grafts. However, once surgically
created, fistulas often fail to develop (mature) into viable points of vascular
access, requiring surgical or radiologic interventions before their use. Because
maturation depends on vascular mechanics (e.g., distensibility and wall shear),
we developed open-source ultrasound software to investigate these metrics
clinically. We demonstrated in a single patient the ability of the software for
consistent measurements from various locations within a cardiac cycle and between
different cardiac cycles. We further assessed the ability of the software to
identify changes in distensibility of a patient's fistula from 1 to 6 weeks
postoperation. The routine frame rates of clinical machines demonstrated high
fidelity tracking within cardiac cycles (coefficient of variation [CV] = 2.4% +/-
0.011) and between cardiac cycles (CV = 2.4% +/- 0.004). The distensibility of
the patient's fistula from 1 to 6 weeks postoperation increased from 4% to 7% in
the arterial inflow and from 3% to 4% in the postarterial anastomotic segment
(PAAS). In contrast, the distensibility of the outflow vein decreased from 4% to
2%. These results corroborate that in addition to diameter changes, the
mechanical properties of the vascular segments changed during fistula maturation.
This demonstrates that our software-based approach may allow ultrasound-based
mechanical measurements to become more accessible for wider clinical research.
PMID- 28489646
TI - Aggressive Hydration With Lactated Ringer Solution in Prevention of
Postendoscopic Retrograde Cholangiopancreatography Pancreatitis.
PMID- 28489645
TI - Portal Vein Thrombosis in Cirrhosis.
AB - Portal vein thrombosis (PVT) in the cirrhotic population is a challenging
clinical phenomenon requiring a nuanced management approach. Uncertainty exists
regarding the clinical significance of PVT in the cirrhotic population because
the data for PVT are based mainly on retrospective, small cohort studies.
Therefore, strong recommendations regarding the optimal timing, modality, and
duration of therapy for PVT in the cirrhotic population cannot be made. However,
this review aims to summarize the current literature and provide stepwise
guidance in diagnosing and managing PVT in patients with cirrhosis.
PMID- 28489647
TI - Obesity/Bariatric Surgery and Crohn's Disease.
AB - BACKGROUND: Crohn's disease (CD) following bariatric surgery has been previously
described. It is not clear whether the clinical entity is due to rapid metabolism
of fat, change in the bacterial milieu of the bowel, the loss of defense
mechanisms of the stomach, or even a coincidence. OBJECTIVES: To present
observations which might serve to sort out these various etiologies. DESIGN: We
present 5 cases of colitis, ileocolitis or enteritis, some with fistula
formation, with clinical onset following bariatric surgery and add these to the 7
cases previously identified as CD reported elsewhere. We provide the clinical
features of these 12 cases to reconcile with causative mechanisms. LIMITATIONS:
It remains possible that the onset of CD (or other inflammatory bowel disease)
precedes the bariatric surgery which then accelerates the clinical manifestations
described. Furthermore, without controls the association could remain a
coincidence. CONCLUSIONS: We review the evidence for release of proinflammatory
cells and cytokines contained in fat following the bariatric surgery, and also
consider the roles that the surgical resection of stomach and shortening of the
bowel may also bring about this syndrome. The earlier onset is more likely due to
surgical loss of defenses of the stomach and the later onset to a metabolic
alteration of the presurgical obesity, involving fat metabolism, and/or the
microbiome. The role of characteristic creeping fat of CD is also addressed.
PMID- 28489648
TI - Clinical Experience With IV Angiotensin II Administration: A Systematic Review of
Safety.
AB - OBJECTIVE: Angiotensin II is an endogenous hormone with vasopressor and endocrine
activities. This is a systematic review of the safety of IV angiotensin II. DATA
SOURCES: PubMed, Medline, Scopus, and Cochrane. STUDY SELECTION: Studies in which
human subjects received IV angiotensin II were selected whether or not safety was
discussed. DATA EXTRACTION: In total, 18,468 studies were screened by two
reviewers and one arbiter. One thousand one hundred twenty-four studies, in which
31,281 participants received angiotensin II (0.5-3,780 ng/kg/min), were selected.
Data recorded included number of subjects, comorbidities, angiotensin II dose and
duration, pressor effects, other physiologic and side effects, and adverse
events. DATA SYNTHESIS: The most common nonpressor effects included changes in
plasma aldosterone, renal function, cardiac variables, and electrolytes. Adverse
events were infrequent and included headache, chest pressure, and orthostatic
symptoms. The most serious side effects were exacerbation of left ventricular
failure in patients with congestive heart failure and bronchoconstriction. One
patient with congestive heart failure died from refractory left ventricular
failure. Refractory hypotensive shock was fatal in 55 of 115 patients treated
with angiotensin II in case studies, cohort studies, and one placebo-controlled
study. One healthy subject died after a pressor dose of angiotensin II was
infused continuously for 6 days. No other serious adverse events attributable to
angiotensin II were reported. Heterogeneity in study design prevented meta
analysis. CONCLUSION: Adverse events associated with angiotensin II were
infrequent; however, exacerbation of asthma and congestive heart failure and one
fatal cerebral hemorrhage were reported. This systematic review supports the
notion that angiotensin II has an acceptable safety profile for use in humans.
PMID- 28489650
TI - Burn Care and Reconstructive Surgery.
PMID- 28489649
TI - A Novel Computerized Test for Detecting and Monitoring Visual Attentional
Deficits and Delirium in the ICU.
AB - OBJECTIVES: Delirium in the ICU is associated with poor outcomes but is under
detected. Here we evaluated performance of a novel, graded test for objectively
detecting inattention in delirium, implemented on a custom-built computerized
device (Edinburgh Delirium Test Box-ICU). DESIGN: A pilot study was conducted,
followed by a prospective case-control study. SETTING: Royal Infirmary of
Edinburgh General ICU. PATIENTS: A pilot study was conducted in an opportunistic
sample of 20 patients. This was followed by a validation study in 30 selected
patients with and without delirium (median age, 63 yr; range, 23-84) who were
assessed with the Edinburgh Delirium Test Box-ICU on up to 5 separate days.
Presence of delirium was assessed using the Confusion Assessment Method for the
ICU. MEASUREMENTS AND MAIN RESULTS: The Edinburgh Delirium Test Box-ICU involves
a behavioral assessment and a computerized test of attention, requiring patients
to count slowly presented lights. Thirty patients were assessed a total of 79
times (n = 31, 23, 15, 8, and 2 for subsequent assessments; 38% delirious).
Edinburgh Delirium Test Box-ICU scores (range, 0-11) were lower for patients with
delirium than those without at the first (median, 0 vs 9.5), second (median, 3.5
vs 9), and third (median, 0 vs 10.5) assessments (all p < 0.001). An Edinburgh
Delirium Test Box-ICU score less than or equal to 5 was 100% sensitive and 92%
specific to delirium across assessments. Longitudinally, participants' Edinburgh
Delirium Test Box-ICU performance was associated with delirium status.
CONCLUSIONS: These findings suggest that the Edinburgh Delirium Test Box-ICU has
diagnostic utility in detecting ICU delirium in patients with Richmond Agitation
and Sedation Scale Score greater than -3. The Edinburgh Delirium Test Box-ICU has
potential additional value in longitudinally tracking attentional deficits
because it provides a range of scores and is sensitive to change.
PMID- 28489651
TI - The Impact of Cervical Musculoskeletal Disorders on UK Consultant Plastic
Surgeons: Can We Reduce Morbidity With Applied Ergonomics?
AB - BACKGROUND: Based on anecdotal and observational evidence, we hypothesized that
the prevalence of cervical musculoskeletal disorder (C-MSD) would be high among
plastic surgeons. A questionnaire review was undertaken to test this hypothesis.
Ergonomic assessment was undertaken to assess causal factors of C-MSD. METHOD: An
anonymous questionnaire recording demographics, physical symptoms and behavioral
responses to C-MSD was distributed to UK Plastic Surgery consultants. The
postural impact of wearing loupes was assessed using motion capture techniques
and recording cervical muscular activity. RESULTS: The questionnaire response
rate was 81%. The prevalence of cervical spine morbidity was recorded as 32%.
Employment implications included 28% of the cohort requiring sick leave. The
professional impact was 7% permanently modifying their practice. There were 2
factors significant for C-MSD, the surgeons' age and the duration in hours of
wearing loupes per week. Ergonomic assessment of surgeons operating in loupes
demonstrated: 1. increased forward and lateral cervical flexion; 2. increased
cervical muscular activity to maintain the protracted "head forward" posture; and
3. prolonged static posturing to maintain head position for visual focus. Table
height adjustment and variation of loupe working distance can reduce neck
flexion. CONCLUSIONS: Cervical morbidity is a prevalent problem among plastic
surgeons. Long procedures, static postures and neck flexion result in the "head
forward" posture. This posture exaggerates when operating with loupe
magnification. Early-middle-aged consultants are more prone to cervical morbidity
hence afflicted when at the top of their game. The work force is diminished for a
potentially avoidable morbidity. Rather than accept this morbidity, co-operation
between plastic surgeons and ergonomist may help to reduce injury.
PMID- 28489652
TI - Histone Deacetylase Inhibitors Enhance Cytotoxicity Towards Breast Tumors While
Preserving the Wound-Healing Function of Adipose-Derived Stem Cells.
AB - INTRODUCTION: Paclitaxel improves the oncologic response of breast cancer
resections; however, it may negatively affect the wound-healing potential of
human adipose-derived stem cells (hASCs) for fat grafting and reconstructive
surgery. Histone deacetylase inhibitors (HDACis) modify the epigenetic regulation
of gene expression and stabilize microtubules similarly to paclitaxel, thus,
creating a synergistic mechanism of cell cycle arrest. We aim to combine these
drugs to enhance cytotoxicity towards breast cancer cells, while preserving the
wound-healing function of hASCs for downstream reconstructive applications.
METHODS: Triple negative breast cancer cells (MBA-MB-231) and hASCs
(institutional review board-approved clinical isolates) were treated with a
standard therapeutic dose of paclitaxel (1.0 MUM) or with low-dose paclitaxel
(0.1 MUM) combined with the HDACi suberoylanilide hydroxamic acid or trichostatin
A. Cell viability, gene expression, apoptosis, and wound-healing/migration were
measured via methylthiazol tetrazolium assay, quantitative real-time polymerase
chain reaction, annexin V assay, and fibroblast scratch assay, respectively.
RESULTS: Combined HDACi and low-dose paclitaxel therapy maintained cytotoxicity
towards breast cancer cells and preserved adipose-derived stem cell viability.
Histone deacetylase inhibitor demonstrated selective anti-inflammatory effects on
adipose-derived stem cell gene expression and decreased expression of the
proapoptotic gene FAS. Furthermore, HDACi therapy did not increase relative
apoptosis within hASCs. A scratch assay demonstrated enhanced wound healing among
injured fibroblasts indirectly co-cultured with HDACi-treated hASCs. CONCLUSIONS:
Combining HDACi with low-dose paclitaxel improved cytotoxicity towards breast
cancer cells and preserved hASC viability. Furthermore, enhanced wound healing
was observed by improved migration in a fibroblast scratch assay. These results
suggest that the addition of HDACi to taxane chemotherapy regimens may improve
oncologic results and wound-healing outcomes after reconstructive surgery.
PMID- 28489656
TI - Consequences of Traumatic Brain Injury in Professional American Football Players:
A Systematic Review of the Literature.
AB - OBJECTIVE: The purpose of this study was to systematically review the literature
for the consequences Traumatic brain injury (TBI) has on cognitive,
psychological, physical, and sports-related functioning in professional American
Football players. DATA SOURCES: We performed a systematic search in 2 databases,
PubMed and SPORTDiscus, to obtain literature from January 1990 to January 2015.
To be eligible for inclusion, a study had to examine the relationship between TBI
and the consequences for several aspects of functioning in professional American
football players older than 18 years. Methodological quality was assessed using a
5-item checklist which assessed selection bias, information bias, and correct
reporting of the population and exposure characteristics. MAIN RESULTS: The
search yielded 21 studies that met our inclusion criteria. An evidence synthesis
was performed on the extracted data and resulted in 5 levels of evidence. The
evidence synthesis revealed that there is strong evidence that concussions are
associated with late-life depression and short-term physical dysfunctions.
Evidence for the relationship between concussion and impaired sports-related
function, prolonged reaction time, memory impairment, and visual-motor speed was
inconclusive. Moderate evidence was found for the association between TBI and
mild cognitive impairment (MCI), and limited evidence was found for the
association between TBI and executive dysfunction. CONCLUSIONS: There is strong
evidence that a history of concussion in American football players is associated
with depression later in life and short-term physical dysfunctions. Also
cognitive dysfunctions such as MCI are seen in older players with a history of
TBI. These results provide input for actions to prevent TBI and their
consequences in (retired) American football players.
PMID- 28489657
TI - The Pattern of Orbital Fractures Managed at Two Referral Centers in Nairobi,
Kenya.
AB - Orbital fractures are one of the commonest injuries in mid-face trauma and can
lead to significant functional and cosmetic defects. This study was aimed at
analyzing the pattern of orbital fractures at 2 referral centers in Nairobi. It
was a descriptive prospective hospital-based study of the demographics, etiology,
clinico-radiological features, and management modalities among patients
presenting with orbital fractures at the University of Nairobi Dental Hospital
and Kenyatta National Referral Hospital in Nairobi, Kenya. A total of 60 patients
(52 males, 8 females; P <0.05) with confirmed orbital fractures were recruited
during the 6-months study period. Orbital fractures occurred most frequently in
the 21 to 40-year-old age group (80%, P<0.05). The principal etiological factors
were motor cycle crashes; 30%, interpersonal violence 23.3%, public vehicle
crushes 20%, private vehicle crushes; 10%, injury from flying objects 10% and
falls 8.3%. The most commonly affected anatomical sites were the floor (75%), the
lateral wall (71.7%), infra-orbital rim (66.7%), zygomatico-frontal suture
(63.3%). There were 5 (8.3%) cases of total blindnessThe impure orbital fractures
that involve the satellite bones especially the zygomatic complex predominate.
PMID- 28489658
TI - Safe and Effective Method to Transfer Pedicle Vessels in Free Flap
Reconstruction.
AB - Free tissue transfer is a useful method to cover soft tissue defects following
trauma or tumor excision. At the time of transfer of the pedicle, its status is
not investigated. Therefore, kinking of the pedicle can occur, and pedicle
injuries can result from surgical instruments. The authors would like to
introduce a simple, safe, and effective method to overcome these problems using a
Penrose drain. The present method can help reconstructive microsurgeons with the
transfer of pedicle vessels through a tunnel without torsion or injury.
PMID- 28489659
TI - Relationship Between the Quantity of Nerve Exposure During Bilateral Sagittal
Split Osteotomy Surgery and Sensitive Recovery.
AB - AIM AND OBJECTIVES: The purpose of this study was to evaluate how different
exposures of the V3 nerves during orthognathic surgery impact neurosensory
disturbances. METHODS: The study included 127 patients who underwent either
bilateral sagittal split osteotomy (BSSO) or BSSO with maxillary le Fort 1. They
were divided into 6 groups, identified by the quantity of V3 nerve exposure. All
patients were examined in a pre-op period and again after 1, 3, 6 months post-op.
The standardized tests used were to clarify the objective and subjective
neurosensory status of the exposed nerve. Neurosensory evaluation included; a pin
prick test, the 2 points discriminator, light touch, warm and cold tests, and
blunt discrimination. They were all done bilaterally on the lower lip area.
RESULTS: In only 2 patients the nerve was damaged during surgery and thus they
were not included in this study. In 10.2% of patients there was no nerve
exposure, 25.2% had longitudinal vestibular segment nerve exposed, 22.8% had the
longitudinal upper-vestibular segment exposed, 20.5% had the longitudinal lower
vestibular segment exposed, 14.2% had the longitudinal upper-lower-vestibular
segment exposed, and in 7.1% of patients the nerve was totally exposed. Given the
estimated time of 1 month there was 100% recovery in patients whose nerve was
unexposed. Considering the other patients, the authors had a variable number of
patients who did not recover completely. CONCLUSION: The authors estimate a
correlation between the recovery time and the quantity of the exposed nerve.
There is a high incidence of neurosensory disturbance in the lower lip and chin
after BSSO and intraoperative quantity of nerve exposure.
PMID- 28489660
TI - Effects of Growth Factors From Platelet-Rich Fibrin on the Bone Regeneration.
AB - Platelet-rich fibrin (PRF) has simple manufacturing process without risk of
immunologic rejection or infection by additional materials. This study was
designed to investigate the effects of platelet-derived growth factors and
transforming growth factors-beta in PRF on the proliferation and differentiation
of osteoblasts. The authors analyzed platelet-derived growth factors and
transforming growth factors-beta in normal human serum (NHS) and PRF by enzyme
linked immunosorbent assay quantitatively and those in PRF group were
significantly increased when compared with NHS. After harvesting osteoblasts from
iliac bone, the authors added 10% fetal bovine serum, 10% NHS, and 3% PRF to
osteoblasts, respectively and incubated for 24, 48, 72 hours. For analysis of
osteoblast proliferation and differentiation, the authors measured DNA synthesis
by [3H]-thymidine isotope activity, protein synthesis by sulforhoamine B assay
and those were increased according to elapsed time in all groups, but they were
significantly increased in 3% PRF. The authors measured alkaline phosphatase
activity of osteoblasts, it was increased according to elapsed to time in all
groups, but significantly increased in 72 hours. In conclusion, application of
PRF to bone defect sites may have an enhanced effect of bone regeneration with
low risk of complications, and relatively simple manufacturing process.
PMID- 28489661
TI - Use of Buccinator Myomucosal Flap in Tongue Reconstruction.
AB - The myomucosal buccinator flap, first described by Bozola in 1989, has become an
important tool for intraoral defects reconstruction. In the literature, there is
a variety of proposed myomucosal cheek flaps, both pedicled and island, based on
the buccal or the facial arteries. From January 2007 to December 2011, the
authors used a pedicled buccinator flap based posteriorly on the buccal artery to
reconstruct partial lingual defects following tumor resection in 27 patients. The
buccal fat pad was translated to cover the donor site defect. After 3 to 4 weeks
from the original surgery, a second procedure under local anesthesia was
performed to detach the pedicle and remodel the flap. The morphological and
functional outcomes of the procedures were evaluated by the surgeons and a speech
and language therapist. All patients presented satisfactory results. The authors
consider the use of the described technique as the gold standard in the
reconstruction of partial tongue defects after tumor resection.
PMID- 28489662
TI - Metastasis of a Renal Collecting Duct Adenocarcinoma to the Oral Cavity After
Tooth Extraction.
AB - Metastatic tumors rarely occur in the oral cavity. The most common of the oral
metastases are lung cancers in males, and breast and genital cancers in females.
The most common primary tumor metastasis to the oral cavity is from the lung,
kidney, liver, prostate, and colorectal cancers. The metastatic lesions are
similar to oral lesions such as pyogenic granuloma, giant cell lesions, gingival
polyps, hemangioma, peripheral fibroma, and adenoid squamous cell carcinoma.
Therefore, the diagnosis of primary tumors is challenging. To our knowledge, this
is the first reported case to feature metastasis of a renal collecting duct
adenocarcinoma to the oral cavity after tooth extraction.
PMID- 28489663
TI - Use-dependent inhibition of glycine-activated chloride current in rat neurons by
beta-amyloid peptide pretreated with hexafluoroisopropanol.
AB - Hexafluoroisopropanol (HFIP) is a nonpolar organic solvent that is often used to
prepare beta-amyloid peptide (Abeta) samples. In this work, we compare the
effects of two different species derived from synthetic Abeta1-42 and prepared
without HFIP (Abeta) or using HFIP (Abeta/HFIP) on the glycine-activated chloride
current (IGly). The experiments were conducted on the pyramidal neurons isolated
from CA3 region of rat hippocampus. Transmembrane currents were recorded using a
conventional patch-clamp technique in the whole-cell configuration. The IGly was
induced by a step application of the agonist for 600 ms through glass capillary.
Abeta or Abeta/HFIP was coapplied with glycine. The effects of the two species of
the peptide have similar and distinctive features. Both substances caused a
reduction in the peak amplitude and an acceleration of desensitization of the
IGly. At the same time, the effect of Abeta/HFIP was found to develop and recover
more slowly and required several repeated applications for its saturation (use
dependence). The effect of Abeta/HFIP was voltage independent and equally
pronounced at negative and positive membrane potentials. First, our results
confirm that HFIP pretreatment may influence the properties of Abeta. Second, new
information on the glycine receptor ability to interact with drugs in use
dependent mode was obtained.
PMID- 28489664
TI - Changes in mitochondrial ultrastructure in SH-SY5Y cells during apoptosis induced
by hemin.
AB - Hemorrhagic stroke is associated with high morbidity and mortality. Hemin is a
decomposition product of hemoglobin that is related to neuronal apoptosis after
hemorrhage, although the molecular basis for this association remains unclear. To
address this issue, the present study investigated hemin-induced changes in the
apoptotic index and mitochondrial ultrastructure in SH-SY5Y cells. Cell viability
was evaluated using Cell Counting Kit-8 and by terminal transferase dUTP nick-end
labeling, western blotting, and flow cytometry. Changes in mitochondrial
ultrastructure were examined by super-resolution three-dimensional structured
illumination microscopy. We found that cleaved-caspase-3 expression and the
number of apoptotic cells increased in a time-dependent manner upon hemin
treatment, which was associated with mitochondrial fragmentation. Our data
suggest that hemin induces apoptosis and mitochondrial fission in neuronal cells.
Thus, therapeutic strategies that target hemin could mitigate the damage caused
by hemorrhagic stroke.
PMID- 28489665
TI - The Nogo receptor inhibits proliferation, migration and axonal extension by
transcriptionally regulating WNK1 in PC12 cells.
AB - Neuronal regeneration and axonal regrowth mechanisms in the injured mammalian
central nervous system are largely unknown. As part of a major pathway for
inhibiting axonal regeneration, activated neuronal glycosylphosphatidylinositol
anchored Nogo receptor (NgR) interacts with LINGO-1 and p75NTR to form a complex
at the cell surface. However, it was found in our previous report that
upregulation of NgR stimulated by injury plays a key role in neuronal
regeneration in the neonatal cortex freeze-lesion model, but its downstream
signalling remains elusive. In the present study, the novel regulatory role of
NgR in a serine-threonine kinase WNK1 was identified. NgR's transcriptional
regulation of WNK1 was identified by RT-qPCR and semiquantitative western blot
after the overexpression or knockdown of NgR, and the regulation is specific to
WNK1, which is not the same for its family members, WNK2, WNK3 and WNK4.
Furthermore, NgR inhibition by NEP fails to affect WNK1, which indicates that
WNK1 functions outside of the Nogo-A/NgR pathway. By performing a proliferation,
migration and axonal extension assay, we also identified that overexpressed NgR
critically regulated these processes and impairment by overexpressing NgR was
rescued with coexpression of WNK1, indicating the partial role of WNK1 in NgR
mediated morphological regulation. Our study identifies a separation of functions
for the NgR-regulated WNK1 in mediating proliferation, migration and axonal
extension in PC12 cells as well as a specific regulatory role between NgR and
WNK1 that is important for recovery from central nervous system injury.
PMID- 28489667
TI - Increasing Levels of Positive End-expiratory Pressure Improve the Left
Ventricular Strain.
AB - PURPOSE: The goal of this study was to evaluate possible changes in the left
myocardial performance of patients with cardiogenic shock (CS) during ascending
levels of positive end-expiratory pressure (PEEP) using speckle-tracking
echocardiography. MATERIALS AND METHODS: This was an interventional clinical
study performed on CS patients under mechanical ventilation. These patients
underwent echocardiography after 15 to 30 minutes of progressive increases in
PEEP zero end-expiratory pressure (ZEEP) (PEEP 5, PEEP 10, PEEP 15 cm H2O). We
evaluated the changes caused by these increasing levels of PEEP on the E/E' ratio
and the parameters of left ventricular systolic and diastolic functions,
including longitudinal strain (S) and strain rate (SR). Analyses of mean values
were carried out using analysis of variance. RESULTS: A total of 65 CS patients
were included. Their mean age was 68.58+/-14.61 years. Progressive increases in
PEEP induced a significant decrease in the E/E' ratio (ZEEP=12.87+/-1.81; PEEP=5,
8.39+/-3.61; PEEP=10, 6.34+/-1.73; and PEEP=15, 7.10+/-0.37; P<0.0001). Although
we did not find significant changes in left ventricular ejection fraction, a
clear increase in left ventricular S and SR occurred (ZEEP=-13, 15+/-1.27;
PEEP=5, -16.97+/-4.01; PEEP=10, -16.89+/-0.46; PEEP=15, -15.39+/-4.21; and ZEEP=
1.02+/-0.02; PEEP=5, -1.49+/-0.13; PEEP=10, -1.57+/-0.21; PEEP=15, -1.24+/-0.29,
respectively; all values were significant). CONCLUSIONS: Increasing levels of
PEEP improve the left ventricular S and SR. PEEP levels could modify the
performance of left ventricular fibers.
PMID- 28489668
TI - Treatment algorithm and management of retrohepatic vena cava injuries.
PMID- 28489669
TI - Rasch validation and comparison of Slovenian, Croatian, and Italian versions of
the Mini-BESTest in patients with subacute stroke.
AB - We aimed to verify by Rasch analysis whether the Mini-BESTest, a balance measure,
confirms its main psychometric properties in patients with subacute stroke
undergoing rehabilitation in three different countries (Slovenia, Croatia, and
Italy), and to examine the stability of item hierarchy and difficulty across the
three national versions through a differential item functioning analysis. We
investigated 159 patients with subacute stroke consecutively admitted to three
rehabilitation facilities after screening for an intensive, tailored
rehabilitation program. Balance function was tested within 36 h from admission
and after ~25 days. As no differential item functioning was found between
admission and discharge data or among countries, all data were pooled. Rasch
criteria for the functioning of rating scale categories were fulfilled. In terms
of internal construct validity, all items except item #14 (Cognitive Get Up & Go;
infit value=1.42) showed an acceptable fit to the Rasch model. The patient
ability-item difficulty matching was very good. Reliability indices were high.
The Principal Component Analysis of standardized residuals confirmed the
unidimensionality of the test. On the basis of the item calibration, raw scores
of the Mini-BESTest were transformed into linear estimates of dynamic balance and
six statistically detectable levels of balance ability were defined. Good
psychometric features of the Mini-BESTest were confirmed. The three different
national versions showed stability in item hierarchy, indicating equivalence of
their cross-cultural adaptations. Problems with item #14 in these patients
warrant further study.
PMID- 28489670
TI - Retrospective Comparison of Fluticasone Propionate and Oral Viscous Budesonide in
Children With Eosinophilic Esophagitis.
AB - BACKGROUND: Eosinophilic esophagitis (EoE) is treated with dietary modification
and/or pharmacologic management with swallowed topical steroids. Swallowed
fluticasone propionate (FP) and oral viscous budesonide (OVB) have proven to be
effective in resolving symptoms and reversing histologic changes in children and
adults with EoE. There are minimal comparative studies between the 2 agents.
OBJECTIVE: The aim of the study was to retrospectively compare endoscopic and
histologic outcomes after FP versus OVB therapy in children with EoE in our
center. METHODS: We performed a retrospective chart review of subjects diagnosed
with EoE at a tertiary care center between 2010 and 2015. Inclusion criteria were
FP or OVB therapy for >=8 weeks along with pre- and post-treatment endoscopic
evaluation. Demographic and clinical features and endoscopic and histologic
assessment were recorded for comparative analysis. Histologic response was
defined as <15 eos/hpf and remission as <5 eos/hpf. RESULTS: The study included
68 EoE patients (20 FP and 48 OVB) with a mean age of 10.6 +/- 5.2 years (range 1
20 years); 81% were boys and 68% were Caucasian. No significant demographic or
clinical differences were noted between the 2 study groups. Overall histologic
response to topical steroids was seen in 44 of 68 (65%) patients. A significantly
greater number of patients achieved histologic response with OVB (36/48, 75%)
than with FP (8/20, 40%) (P = 0.0059). Mean pretreatment peak eos/hpf was 46 +/-
19 in the FP group versus 45 +/- 23 in the OVB group. Mean post-treatment peak
eos/hpf was 20 +/- 29 in the FP group versus 12 +/- 16 in the OVB group (P =
0.002). There was also a significantly greater difference in the change of
absolute eos/hpf from pre- to post-treatment in the OVB group (-33) versus FP
(18) (P = 0.047). A greater number of OVB-treated patients without asthma had a
histologic response compared to those with asthma (P = 0.031). The response to
OVB was not affected by the delivery vehicle, namely sucralose (Splenda) versus
Neocate Duocal. CONCLUSIONS: Our data suggest that treatment with OVB leads to
better endoscopic and histologic outcomes than FP. Adherence to treatment and
history of asthma are major determining factors in the response to treatments.
Using Neocate Duocal as the OVB delivery vehicle is just as effective as
sucralose.
PMID- 28489671
TI - Closer Look at the Nutritional Outcomes of Patients After Primary Repair of
Congenital Diaphragmatic Hernia.
AB - OBJECTIVES: We hypothesize that the patients after primary repair of congenital
diaphragmatic hernia (CDH) can have poor nutritional outcomes and plan to
identify risk factors to further stratify these patients. METHODS: Retrospective
cohort of patients who had primary repair of CDH between 2000 and 2014 and had
follow-up at our institution. Z scores (weight for age and weight for length)
were calculated using the World Health Organization and Centers for Disease
Control and Prevention growth standards. RESULTS: For the 67 patients in the
cohort, the median age at the time of repair was 3 days (interquartile range 2-5)
and at the time of discharge was 20.5 days (interquartile range 16-30). Fifteen
percent of the patients required supplemental tube feeding for inadequate oral
intake and 69% required fortified feedings for inadequate growth at discharge (4
patients subsequently needed gastrostomy tube placement). The median z scores at
discharge were -1.0 (-2.1 to -0.3) and -1.2 (-2.3 to -0.5) in weight for age and
weight for length, respectively. The risk factors for low z scores included open
repair and longer periods of postoperative intubation or hospitalization. The z
scores were similar at 6 months of age compared to discharge, but then
statistically improved at 12 months of age. CONCLUSIONS: Patients with primary
repair of CDH are at risk for poor nutritional outcomes at the time of hospital
discharge and require follow-up to ensure adequate growth. Patients at highest
risk are those who had an open repair and had prolonged intubation or
hospitalization.
PMID- 28489672
TI - Starved Guts: Morphologic and Functional Intestinal Changes in Malnutrition.
AB - Malnutrition contributes significantly to death and illness worldwide and
especially to the deaths of children younger than 5 years. The relation between
intestinal changes in malnutrition and morbidity and mortality has not been well
characterized; however, recent research indicates that the functional and
morphologic changes of the intestine secondary to malnutrition itself contribute
significantly to these negative clinical outcomes and may be potent targets of
intervention. The aim of this review was to summarize current knowledge of
experimental and clinically observed changes in the intestine from malnutrition
preclinical models and human studies. Limited clinical studies have shown villous
blunting, intestinal inflammation, and changes in the intestinal microbiome of
malnourished children. In addition to these findings, experimental data using
various animal models of malnutrition have found evidence of increased intestinal
permeability, upregulated intestinal inflammation, and loss of goblet cells. More
mechanistic studies are urgently needed to improve our understanding of
malnutrition-related intestinal dysfunction and to identify potential novel
targets for intervention.
PMID- 28489674
TI - Differentiation Between Crohn Disease and Intestinal Tuberculosis in Children.
AB - OBJECTIVES: The aim of the study was to evaluate clinical, endoscopic,
radiologic, and histopathological features helpful in differentiating Crohn
disease (CD) from intestinal tuberculosis (ITB) in children. METHODS: Patients
diagnosed to have CD or ITB based on standard recommended criteria were enrolled.
Children with inflammatory bowel disease unclassified or suspected ITB or CD with
incomplete work-up or lost to follow-up were excluded. The clinical and
laboratory (radiology, endoscopy, and histology) details of children were
analyzed. RESULTS: Twenty cases of ITB (14 [3-17] years) and 23 of CD (11 [1-17]
years) were enrolled. Presentation with chronic diarrhea (82% vs 40%; P = 0.006)
and blood in stool (74% vs 10%; P = 0.001) favored CD, whereas subacute
intestinal obstruction (20% vs 0%; P = 0.04) and ascites (30% vs 0%; P = 0.005)
favored ITB. Presence of deep ulcers (61% vs 30%; P = 0.04), longitudinal ulcers
(48% vs 15%; P = 0.02), involvement of multiple colonic segments (70% vs 35%; P =
0.02), left-sided colon (87% vs 40%; P = 0.003), extraintestinal manifestations
(21.7% vs 0%; P = 0.02), and higher platelet count (3.9 vs 2.6 * 10/mm; P = 0.02)
favored CD. Isolated ileocecal involvement (40% vs 8.7%; P = 0.03) was a feature
of ITB. TB bacilli were demonstrated in 40% ITB cases (colon-6, ascites-1,
abdominal lymph node-1). On multivariate analysis, presence of blood in stool
(odds ratio: 37.5 [confidence interval: 3.85-365.72], P = 0.002) and left-sided
colonic involvement (odds ratio: 16.2 [confidence interval: 1.63-161.98], P =
0.02) were independent predictors of CD. CONCLUSIONS: Microbiologic confirmation
of tuberculosis is possible in 40% ITB cases. Presence of blood in stool and left
sided colonic involvement are the most important features favoring CD.
PMID- 28489675
TI - No Need for Routine Endoscopy in Children With Celiac Disease on a Gluten-free
Diet.
PMID- 28489676
TI - Suprapubic Catheter Change Methods: A Crossover Comparison Cohort Trial.
AB - PURPOSE: The purpose of this study was to compare 2 methods of suprapubic
catheter (SPC) change, instillation and observation. The instillation method
requires instillation of saline to the bladder prior to SPC removal; the
observation method is completed taking note of the angle and length at which the
indwelling SPC is withdrawn and observation of urine from the newer catheter when
inserted. DESIGN: Nonrandomized crossover trial. SUBJECTS AND SETTING: Fifty-nine
community-dwelling adults who were long-term SPC users participated in the study.
There were 38 males and 21 females, with a mean age of 68.5 years. Most had
chronic, progressive, or complex comorbidity. The mean duration of SPC use was
3.5 years. METHODS: Participants underwent 4 SPC changes using the instillation
method, followed by 4 changes using the observation method. Data were collected
using a 3-part survey document; it queried demographic and catheter-related
clinical information, the number of symptomatic catheter-associated urinary tract
infections (CAUTIs) requiring antibiotic treatment, the number of catheter
blockages that occurred during data collection, and nurses' experiences during
catheter changes (including narrative feedback-related problems, concerns, or
comments in relation to each catheter change). The comparative CAUTI and blockage
outcomes were analyzed using McNemar's test for 2 paired samples. Narrative data
were analyzed using thematic analysis. RESULTS: There were 231 SPC changes using
the observation method. No episodes of catheter displacement occurred. Analysis
of nurses' narrative revealed concerns regarding "slowness" of urine drainage
from the newly inserted catheter. This concern was addressed by promotion of
adequate hydration prior to catheter change. There were 120 paired useable
surveys included in the CAUTI and blockage incidence comparison; no statistically
significant differences in CAUTI occurrences were found based on catheter change
method (11 vs 11, P = .7728). No differences in the catheter blockage episodes
were found based on catheter change method (8 vs 6, P = .7237). CONCLUSION: The
observation method of SPC change was as effective as the instillation method.
PMID- 28489677
TI - Futility of imaging to stage melanoma patients with a positive sentinel lymph
node.
AB - The use of staging imaging in melanoma patients with a positive sentinel lymph
node (SLN) has been reported to be of limited value. Improved accuracy resulting
from the development of time-of-flight positron emission tomography (PET) and
ongoing image quality improvement of computed tomography (CT) may challenge this
statement. Our retrospective study assessed the clinical value of routine staging
CT and PET/CT imaging in a recent cohort of asymptomatic SLN-positive patients.
Between January 2011 and April 2014, 143 patients with a positive SLN were
routinely staged using CT of various parts of the body or whole-body PET/CT.
Scores were assigned for level of certainty for regional or distant metastases
and incidental second primary malignancies. Diagnostic test performance was
assessed, as well as the number and nature of ensuing additional diagnostic
actions. CT was performed in 102 of 143 (71%) patients and PET/CT in 41 (29%)
patients. The use of PET/CT increased over the study period. Metastases were
found in two of the 143 patients (true-positive yield 1.4%). Sensitivity,
specificity and positive predictive value were 11, 73 and 4% for CT and 17, 57
and 6%, respectively, for PET/CT. None of the 143 patients had a change in AJCC
stage. Two other primary malignancies were found. Twenty-one (15%) patients were
subjected to 37 additional investigations, referrals or procedures. Routine
staging imaging with CT or PET/CT in SLN-positive patients is not useful. The
yield is low and the results are often false positive, leading to unnecessary
additional tests, most of which are costly and some potentially morbid.
PMID- 28489678
TI - Safety and efficacy of the antiganglioside GD3 antibody ecromeximab (KW2871)
combined with high-dose interferon-alpha2b in patients with metastatic melanoma.
AB - This study evaluated the safety and clinical benefit of ecromeximab (KW2871)
combined with high-dose interferon-alpha2b (HDI) in patients with metastatic
melanoma. We also carried out pharmacokinetic and immune monitoring studies of
this combination. This was an open-label, phase 1/2 study of ecromeximab plus HDI
in patients with measurable metastatic melanoma. Eligible patients received
ecromeximab-HDI combination therapy: ecromeximab administered intravenously once
every 2 weeks and HDI at a dose of 20 million units (MU)/m administered
intravenously for 5 consecutive days per week for the first 4 weeks (induction
phase) and then at 10 MU/m subcutaneously thrice weekly through week 14
(maintenance phase). Patients were treated with combination therapy until disease
progression or limiting toxicity. Three dose-escalation cohorts (5, 10, and 20
mg/m) of ecromeximab were planned. Thirty-six evaluable patients were enrolled
including six in each of cohorts 1 and 2, and 24 in cohort 3. Median progression
free survival was 2.53 months [95% confidence interval (CI):1.93-3.83] and it was
1.93 months (95% CI: 1.00-3.80) in cohort 3. The median overall survival was
10.28 months (95% CI: 6.93-16.77) and 7.78 months (95% CI: 6.03-13.97) in cohort
3. There was no significant difference in progression-free survival or overall
survival by BRAF mutation status. The response rate was 5.6% (95% CI: 0.68-18.7),
with two patients showing an objective response (one complete response and one
partial response), and the clinical benefit rate was 78% (95% CI: 61-90). Stable
disease as best response was observed in 26 (72%) patients including five in each
of cohorts 1 and 2, and 16 in cohort 3. Treatment-emergent adverse events
considered related to ecromeximab treatment occurred in four (66.7%) patients in
cohort 1, five (83.3%) patients in cohort 2, and seven (29.2%) patients in cohort
3. Among TEAEs with a maximum severity of grade 3 or 4, those that occurred only
in cohort 3 were related to pain, electrolyte imbalance, blood cell decreases,
and allergic reaction. Safety and efficacies considered related to ecromeximab
occurred in cohort 3 and included grade 3 hypersensitivity [one (4.2%)] and grade
2 hypotension [one (4.2%)]. Regimen-limiting toxicities occurred in two (8.3%)
patients in cohort 3: hypersensitivity (with hypertension, supraventricular
tachycardia, bronchospasm, chills, and dyspnea) and hypotension. One patient out
of 31 examined showed a low-level transient positivity for human antichimeric
antibodies against ecromeximab. Pharmacokinetic measurements by enzyme-linked
immunosorbent assay determined that administration of HDI does not influence
serum levels of ecromeximab at 5, 10, and 20 mg/m dose levels. Ecromeximab in
combination with HDI was generally well tolerated in patients with metastatic
melanoma and has shown low immunogenicity. However, the clinical activity was
limited, suggesting that future development of this combination should be
deprioritized and that other combinations, such as with immune checkpoint
inhibitors, should be considered.
PMID- 28489679
TI - Ipilimumab-associated cholestatic hepatitis: a case report and literature review.
AB - Ipilimumab is a monoclonal antibody that exerts its effects by inhibiting the
cytotoxic T-lymphocyte-associated protein 4 receptor on cytotoxic T lymphocytes.
It is frequently used for the treatment of unresectable or metastatic melanoma.
Ipilimumab may lead to several immune-related disease including colitis,
thyroiditis, pneumonia, hepatitis, or pancreatitis as a side effect. Limited
number of cases with hepatic damage as an ipilimumab-related adverse event has
been reported in the literature. This agent has been implicated in causing acute
hepatitis-like liver injury. Here, we presented a case in which cholestatic
hepatitis developed during ipilimumab use for the treatment of metastatic
melanoma.
PMID- 28489680
TI - Cyclic AMP-Epac signaling pathway contributes to repression of PUMA transcription
in melanoma cells.
AB - The universal second messenger cAMP regulates numerous cellular processes.
Although the cAMP-signaling pathway leads to induction of gene transcription, it
remains unknown whether this pathway contributes toward suppression of
transcription. Here, we show that blockade of cAMP signaling using MDL12330A led
to an increase in PUMA transcript levels, but not p21 in melanoma cells. cAMP
downstream component Epac activation was essential for suppression of PUMA
transcription as an Epac agonist reversed the effects of MDL12330A. These results
suggest that transcriptional repression is one of the functions of the cAMP-Epac
signaling pathway.
PMID- 28489681
TI - Temporal Stress in the Operating Room: Brain Engagement Promotes "Coping" and
Disengagement Prompts "Choking".
AB - OBJECTIVE: To investigate the impact of time pressure (TP) on prefrontal
activation and technical performance in surgical residents during a laparoscopic
suturing task. BACKGROUND: Neural mechanisms enabling surgeons to maintain
performance and cope with operative stressors are unclear. The prefrontal cortex
(PFC) is implicated due to its role in attention, concentration, and performance
monitoring. METHODS: A total of 33 residents [Postgraduate Year (PGY)1-2 = 15,
PGY3-4 = 8, and PGY5 = 10] performed a laparoscopic suturing task under "self
paced" (SP) and "TP" conditions (TP = maximum 2 minutes per knot). Subjective
workload was quantified using the Surgical Task Load Index. PFC activation was
inferred using optical neuroimaging. Technical skill was assessed using
progression scores (au), error scores (mm), leak volumes (mL), and knot tensile
strengths (N). RESULTS: TP led to greater perceived workload amongst all
residents (mean Surgical Task Load Index score +/- SD: PGY1-2: SP = 160.3 +/-
24.8 vs TP = 202.1 +/- 45.4, P < 0.001; PGY3-4: SP = 123.0 +/- 52.0 vs TP = 172.5
+/- 43.1, P < 0.01; PGY5: SP = 105.8 +/- 55.3 vs TP = 159.1 +/- 63.1, P < 0.05).
Amongst PGY1-2 and PGY3-4, deterioration in task progression, error scores and
knot tensile strength (P < 0.05), and diminished PFC activation was observed
under TP. In PGY5, TP resulted in inferior task progression and error scores (P <
0.05), but preservation of knot tensile strength. Furthermore, PGY5 exhibited
less attenuation of PFC activation under TP, and greater activation than either
PGY1-2 or PGY3-4 under both experimental conditions (P < 0.05). CONCLUSIONS:
Senior residents cope better with temporal demands and exhibit greater technical
performance stability under pressure, possibly due to sustained PFC activation
and greater task engagement. Future work should seek to develop training
strategies that recruit prefrontal resources, enhance task engagement, and
improve performance under pressure.
PMID- 28489682
TI - Personalised Prehabilitation in High-risk Patients Undergoing Elective Major
Abdominal Surgery: A Randomized Blinded Controlled Trial.
AB - OBJECTIVE: The aim of this study was to assess the impact of personalized
prehabilitation on postoperative complications in high-risk patients undergoing
elective major abdominal surgery. SUMMARY BACKGROUND DATA: Prehabilitation,
including endurance exercise training and promotion of physical activity, in
patients undergoing major abdominal surgery has been postulated as an effective
preventive intervention to reduce postoperative complications. However, the
existing studies provide controversial results and show a clear bias toward low
risk patients. METHODS: This was a randomized blinded controlled trial. Eligible
candidates accepting to participate were blindly randomized (1:1 ratio) to
control (standard care) or intervention (standard care + prehabilitation) groups.
Inclusion criteria were: i) age >70 years; and/or, ii) American Society of
Anesthesiologists score III/IV. Prehabilitation covered 3 actions: i)
motivational interview; ii) high-intensity endurance training; and promotion of
physical activity. The main study outcome was the proportion of patients
suffering postoperative complications. Secondary outcomes included the endurance
time (ET) during cycle-ergometer exercise. RESULTS: We randomized 71 patients to
the control arm and 73 to intervention. After excluding 19 patients because of
changes in the surgical plan, 63 controls and 62 intervention patients were
included in the intention-to-treat analysis. The intervention group enhanced
aerobic capacity [DeltaET 135 (218) %; P < 0.001), reduced the number of patients
with postoperative complications by 51% (relative risk 0.5; 95% confidence
interval, 0.3-0.8; P = 0.001) and the rate of complications [1.4 (1.6) and 0.5
(1.0) (P = 0.001)] as compared with controls. CONCLUSION: Prehabilitation
enhanced postoperative clinical outcomes in high-risk candidates for elective
major abdominal surgery, which can be explained by the increased aerobic
capacity.
PMID- 28489683
TI - Intraoperative Use of Vasopressors Does Not Increase the Risk of Free Flap
Compromise and Failure in Cancer Patients.
AB - OBJECTIVE: To examine the effects of vasopressors on free flap outcomes.
BACKGROUND: Most micro-surgeons avoid the use of vasopressors during free flap
surgery due to concerns of vasoconstriction, which could potentially lead to
vascular thrombosis and flap failure. Previous studies lack the statistical power
to draw meaningful conclusions. METHODS: All free flaps between 2004 and 2014
from a single institution were reviewed retrospectively. Vasopressors were given
intraoperatively as an intravenous bolus when blood pressure dropped >20% from
baseline. The timing of intraoperative vasopressor administration was divided
into 3 phases: from anesthesia induction to 30 minutes before the start of flap
ischemia (P1); end of P1 to 30 minutes after revascularization (P2); end of P2 to
end of surgery (P3). Agents included phenylephrine, ephedrine and calcium
chloride. RESULTS: A total of 5671 free flap cases in 4888 patients undergoing
head and neck, breast, trunk, or extremity reconstruction were identified.
Vasopressors were used intraoperatively in 85% of cases. The overall incidence of
pedicle compromise was 3.6%, with a flap loss rate of 1.7%. A propensity score
matching analysis showed that intraoperative use of any agents at any time of
surgery was not associated with increased overall pedicle compromise [51/1584
(3.2%) vs 37/792 (4.7%); P = 0.074] or flap failure rates [26/1584 (1.6%) vs
19/792 (2.4%); P = 0.209]. Rather, there was less risk of venous congestion
[33/1584 (2.1%) vs 31/792 (3.9%); P = 0.010]. CONCLUSIONS: Intraoperative use of
phenylephrine, ephedrine, or calcium chloride as an intravenous bolus does not
increase flap compromise and failure rates in cancer patients.
PMID- 28489685
TI - Solid Organ Laceration in an Adolescent Soccer Player: A Case Report.
AB - : Pediatric solid organ lacerations are a relatively uncommon but potentially
dangerous injury that must be addressed urgently once recognized. Seen most often
during recreational or team sports, they usually occur after a blunt or
deceleration mechanism to the abdomen or flank. Depending on the severity of
injury, solid organ laceration may not be immediately apparent clinically. This
emphasizes the importance of sideline witnessing and evaluation, acting quickly
once symptoms develop, and placing importance on safe sporting technique. In
addition, management has changed over time to favor medical management for minor
injuries, with laparotomy reserved for high-grade or hemodynamically unstable
lacerations. Awareness of solid organ laceration in pediatric populations is more
important than ever as they are beginning to appear in younger adolescents. Here
we present a case of a 14-yr-old girl sustaining a grade IV liver laceration
while playing contact team sports.
PMID- 28489684
TI - Calculated versus Measured MVV-Surrogate Marker of Ventilatory Capacity in
Pediatric CPET.
AB - INTRODUCTION: Maximum voluntary ventilation (MVV), a surrogate marker of maximum
ventilatory capacity, allows for measuring ventilatory reserve during
cardiopulmonary exercise testing (CPET), which is necessary to assess ventilatory
limitation. MVV can be measured directly during a patient maneuver or indirectly
by calculating from forced expiratory volume in 1 s (FEV1 * 40). We investigated
for a potential difference between calculated MVV and measured MVV in pediatric
subjects, and which better represents maximum ventilatory capacity during CPET.
METHODS: Data were collected retrospectively from CPET conducted in pediatric
subjects for exercise-induced dyspnea from January 2014 to June 2015 at Akron
Children's Hospital. Subjects with neuromuscular weakness, morbid obesity, and
suboptimal effort during the testing were excluded from the study. RESULTS:
Thirty-five subjects (mean +/- SD, age = 13.8 +/- 2.7 yr, range = 7-18 yr)
fulfilled the criteria. Measured MVV was significantly lower than calculated MVV
(89.9 +/- 26.4 vs 122.4 +/- 34.5 L.min; P < 0.01). The ventilatory reserve based
on measured MVV was also significantly lower than ventilatory reserve based on
calculated MVV (12.4% +/- 19.6% vs 36.1% +/- 13.2%; P < 0.01). Calculated MVV (as
well as ventilatory reserve based on calculated MVV) was significantly correlated
with ventilatory parameters. By contrast, no significant correlations were found
between measured MVV (or ventilatory reserve based on measured MVV) and
ventilatory parameters except for peak ventilation (peak VE). CONCLUSIONS: The
measured MVV was significantly lower than the calculated MVV in our pediatric
subjects. The calculated MVV was a better surrogate of maximum ventilatory
capacity as shown by significant correlation to other ventilatory parameters
during CPET.
PMID- 28489686
TI - Scaling the Oxygen Uptake Efficiency Slope for Body Size in Cystic Fibrosis.
AB - PURPOSE: The aim of this study was to describe the relationship between body size
and oxygen uptake efficiency slope (OUES) in pediatric patients with cystic
fibrosis (CF) and healthy controls (CON), to identify appropriate scaling
procedures to adjust the influence of body size upon OUES. METHODS: The OUES was
derived using maximal and submaximal points from cardiopulmonary exercise testing
in 72 children (36 CF and 36 CON). OUES was subsequently scaled for stature, body
mass (BM), and body surface area (BSA) using ratio-standard (Y/X) and allometric
(Y/X) methods. Pearson's correlation coefficients were used to determine the
relationship between body size and OUES. RESULTS: When scaled using the ratio
standard method, OUES had a significant positive relationship with stature (r =
0.54, P < 0.001) and BSA (r = 0.25, P = 0.031) and significant negative
relationship with BM (r = -0.38, P = 0.016) in the CF group. Combined allometric
exponents (b) for CF and CON were stature 3.00, BM 0.86, and BSA 1.40. A
significant negative correlation was found between OUES and stature in the CF
group when scaled allometrically (r = -0.37, P = 0.027). Nonsignificant (P >
0.05) correlations for the whole group were found between OUES and allometrically
scaled BM (CF r = -0.25, CON, r = 0.15) and BSA (CF r = -0.27, CON r = 0.13).
CONCLUSIONS: Only allometric scaling of either BM or BSA, and not ratio-standard
scaling, successfully eliminates the influence of body size upon OUES. Therefore,
this enables a more direct comparison of the OUES between patients with CF and
healthy controls.
PMID- 28489687
TI - Consistently High Level of Cardiorespiratory Fitness and Incidence of Type 2
Diabetes.
AB - PURPOSE: Although the benefit of high cardiorespiratory fitness (CRF) for the
prevention of type 2 diabetes mellitus (T2DM) is widely accepted, whether
consistently high CRF is necessary or transiently high CRF is sufficient is
unclear. The present study was conducted to examine the hypothesis that
consistently high level of CRF is more beneficial than transiently high CRF for
the prevention of T2DM. METHODS: This cohort study was conducted in nondiabetic
7158 men age 20 to 60 yr, enrolled from 1986 to 1987. The area under the curve
with respect to ground (AUCG) for CRF measurements during an 8-yr measurement
period (1979-1987) was calculated as an index of integrated CRF level during the
period. The differences (DeltaAUCP) between AUCG and peak AUC (peak CRF
measurement period) was also calculated as an index of the presence and the size
of a "spike" in CRF. T2DM was defined by fasting blood glucose and a self
reported diagnosis of diabetes for participants with blood tests. For
participants without blood tests, T2DM was defined by the result of oral glucose
test after a nonfasting urinary test and a self-reported diagnosis of diabetes.
T2DM was determined on health checkups until 2009. RESULTS: During the follow-up
period, 1495 men developed T2DM. After adjustment for confounders, as compared
with the first quartile of AUCG for CRF, the hazard ratio (95% confidence
interval) for the second, third, and fourth quartiles were 0.87 (0.76 to 1.00),
0.80 (0.68 to 0.95), and 0.72 (0.58 to 0.89), respectively. For CRF spike, there
was no association between DeltaAUCP in CRF and the incidence of T2DM.
CONCLUSIONS: Consistently higher level of CRF over time was associated with lower
risk of T2DM.
PMID- 28489688
TI - Hybrid PET/MRI-based delineation of gross tumor volume in head and neck cancer
and tumor parameter analysis.
AB - OBJECTIVES: Accurate target delineation allows an increase in radiation dose to
the target tumor while reducing damage to the surrounding normal tissue. However,
there is currently no standard for evaluating volumes measured by different
imaging modalities. The aim of this study is to evaluate the feasibility of
contouring gross tumor volume (GTV) by PET/MRI in head and neck cancer, and to
define an adaptive threshold level (aTL) for delineating the biological target
volume (BTV). PATIENTS AND METHODS: Eighteen head and neck cancer patients
underwent time of flight PET/MRI before chemoradiotherapy. Different GTVs of
primary tumors and metastatic lymph nodes were manually contoured on MRI
(GTVMRI), PET (GTVVIS), and fused PET/MRI (GTVFUS). An MRI-based GTV contour was
substituted for the pathologic GTV. The percentile threshold boundary of the
maximum standardized uptake value (SUVmax) for the BTV was determined when the
volume of BTV approached that of GTVMRI. RESULTS: All GTVs were highly correlated
(all Pearson's r>0.85, all P<0.001). Tumor diameter strongly correlated with GTVs
(r=0.7-0.8 for all lesions and primary tumor; r=0.8-0.9 for lymph node
metastases). aTL and SUVmax were moderately correlated for all lesions (r=-0.692,
P<0.001) and were strongly correlated for primary tumors (r=-0.866, P<0.001).
CONCLUSION: Delineating GTV on hybrid PET/MRIs is feasible, and aTL, the
threshold boundary of BTV, was correlated inversely with the SUVmax.
PMID- 28489689
TI - Half-body single photon emission computed tomography with resolution recovery for
the evaluation of metastatic bone disease: implementation into routine clinical
service.
AB - OBJECTIVES: Typically, scintigraphic evaluation of metastatic bone disease uses
planar imaging. Although single photon emission computed tomography (SPECT)
offers increased clinical utility, the acquisition time necessary to cover the
required scan range (at our centre, skull vertex to mid-femur) has made its use
in place of planar imaging impracticable. Recently, reconstruction with
resolution recovery (RR) has allowed SPECT acquisition times to be shortened
while maintaining acceptable image quality. This study was carried out to
establish whether half-body SPECT with RR could replace planar scintigraphy in
routine practice. METHODS: A series of reduced acquisition time SPECT scans were
reconstructed retrospectively and reviewed to establish optimal reconstruction
parameters. Twenty patients referred for evaluation of bone metastases underwent
planar imaging, followed by half-body SPECT, reconstructed using the optimized
parameters. SPECT and planar images were reported by an experienced radiologist,
who reviewed image quality and recorded the number of lesions observed, their
location, clinical significance and reporter confidence. RESULTS: SPECT images of
acceptable quality and covering the range from skull vertex to mid-femur were
acquired in 33 min. Audit indicated that SPECT identified clinically significant
lesions not reported from planar views and improved lesion localization and
reporter confidence. CONCLUSION: Reduced acquisition times together with RR
allowed half-body SPECT for the evaluation of bone metastases to be accommodated
within our department's schedule. Audit indicated that SPECT delivered the
expected clinical advantages. Half-body SPECT has replaced planar imaging for the
routine evaluation of metastatic bone disease at our centre, with ~2500 studies
carried out to date.
PMID- 28489690
TI - Measurement uncertainty of lesion and reference mediastinum standardized uptake
value in lung cancer.
AB - OBJECTIVE: To assess standardized uptake value (SUV) measurement uncertainty (MU)
of lung cancer lesions with uptake greater than mediastinum but less than or
equal to the liver and that of the mediastinum blood pool, and to compare lesion
SUV with mediastinum SUV by assessing MU of their ratio. PATIENTS AND METHODS:
Dynamic PET data involving 10 frames were retrospectively analyzed in 10
patients, yielding maximal SUV of 25 lesions (Lesion-SUVmax), 10 mediastinum SUV,
either maximal or mean (Med-SUVmax, Med-SUVmean), 25 Rmax ratios (=Lesion
SUVmax/Med-SUVmax), and 25 Rmean ratios (=Lesion-SUVmax/Med-SUVmean). A mean
coefficient of variation was calculated for each parameter, leading to relative
measurement uncertainty (MUr), respectively. RESULTS: MU of Rmax was found to
involve both Lesion-SUVmax and Med-SUVmax MU: MUr=33.3-23.3-21.9%, respectively
(95% confidence level). No significant difference in MUr was found between Med
SUVmax and Med-SUVmean and between Rmax and Rmean. CONCLUSION: Comparison between
target lesion SUV and reference mediastinum SUV must take into account SUV MU of
both. Therefore, no MU reduction can be expected from using the
lesion/mediastinum SUVmax ratio instead of Lesion-SUVmax. Moreover, no MU
reduction can be expected from using the mean mediastinum SUV instead of the
maximal one.
PMID- 28489691
TI - Optimal injected dose ratio of a very rapid 1-day protocol of myocardial
perfusion imaging with cadmium-zinc-telluride single-photon emission tomography:
simulation and phantom study.
AB - OBJECTIVE: Cadmium-zinc-telluride detectors enable shorter acquisition durations
in myocardial perfusion imaging (MPI), but the time interval of sequential
scanning is still unchanged in clinical practice. We designed a very rapid 1-day
protocol of MPI using cadmium-zinc-telluride single-photon emission tomography
and evaluated the optimal dose ratio between two scanning acquisitions by means
of simulations and phantom experiments. METHODS: We intended to perform a 1-day
MPI within 140 min and simulate radioactivities in the second scan under various
injected dose ratios. To apply this, a cardiac phantom was scanned with various
radioactivities and scans were compared with a reference scan with the ideal
tracer concentrations. RESULTS: In the stress-first protocol, the dose ratio 1 :
5 was enough to show the same regional percentage uptake compared with the
reference. However, in the rest-first protocol, the regional percentage uptakes
were higher than those of the reference image even with a 1 : 6 dose ratio.
CONCLUSION: The injected dose ratio 1 : 5 is optimal in a stress-first rapid 1
day protocol. The rest-first protocol is not appropriate because a dose ratio
greater than 1 : 6 is required to withdraw shine-through artifacts.
PMID- 28489692
TI - TREATMENT OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION PATIENTS WITH VASCULAR
ENDOTHELIAL GROWTH FACTOR INHIBITORS IN EVERYDAY PRACTICE: Identification of
Health Care Constraints in Germany-The PONS Study.
AB - PURPOSE: The PONS study was conceived to analyze the extent of nonpersistence
(NP) and nonadherence (NA) in the treatment of patients with neovascular age
related macular degeneration in everyday clinical practice in Germany. Further
objectives were to identify factors that can affect NP and NA and to analyze
clinical outcomes under everyday conditions. METHODS: Nonpersistence (no contact
with doctor for at least 3 months) and NA (no treatment or follow-up for at least
6 weeks) as well as clinical data were analyzed up to 24 months retrospectively
and 12 months prospectively in 480 patients with neovascular age-related macular
degeneration in 23 treatment centers. Patients were interviewed for factors
possibly affecting NP and NA. RESULTS: One third of patients fulfilled criteria
of NA in the first 3 months and two thirds after 6 months. The NP was 18.8% after
12 months. Treatment exclusively at one center, a higher number of patients with
neovascular age-related macular degeneration at the treating center, and fixed
appointments were associated with a lower risk for NP. An initial gain in visual
acuity after upload was not preserved after 12 months (mean change -0.5 Early
Treatment Diabetic Retinopathy Study letters). Whereas visual acuity declined by
7.5 Early Treatment Diabetic Retinopathy Study letters in patients with good
baseline visual acuity >20/40, visual acuity improved by 8.5 letters in patients
with baseline visual acuity of <=20/200. Only 7.5% of patients underwent an
optical coherence tomography scan after 3 upload injections, and only 2.0 optical
coherence tomographies were performed in the first 12 months. CONCLUSION: The NP
and NA were high in our study population and are likely to have contributed to a
suboptimal clinical outcome compared with randomized clinical trials.
Shortcomings in the management of patients with neovascular age-related macular
degeneration, including restrictions in the timely and adequate follow-up
(including optical coherence tomography) and retreatment, appear to be
constraining factors in Germany.
PMID- 28489693
TI - DYSFUNCTIONAL AUTONOMIC REGULATION OF THE CHOROID IN CENTRAL SEROUS
CHORIORETINOPATHY.
AB - PURPOSE: To study the effect of changing perfusion pressures on retinal and
choroidal structure in central serous chorioretinopathy (CSC). METHODS: This
prospective observational case series included seven healthy volunteers (14 eyes)
and seven patients (14 eyes) with CSC. Each patient underwent spectral domain
optical coherence tomography with enhanced depth imaging in the upright (sitting)
and supine positions. Image segmentation focused on central macular thickness,
subretinal fluid, total macular volume, choroidal thickness, and choriocapillaris
thickness. Blood pressure and heart rate were measured in the upright and supine
positions. RESULTS: Choriocapillaris thickness was thicker in CSC participants
(34.23 MUm; range, 30.9-36.5 MUm) compared with healthy controls (13.96 MUm;
range, 7.15-23.87 MUm) (P <= 0.001). The choroid was similarly thicker in CSC
participants (371.4 MUm; range, 200.2-459.4 MUm) compared with healthy controls
(231.4 MUm; range 161.8-287.5 MUm) (P <= 0.001). Choroidal thickness increased in
patients with CSC when transitioning from upright (371.4 MUm) to supine (377.8
MUm) (P <= 0.01). By contrast, there was an 11.97% decrease in choroid thickness
in normal controls when transitioning from upright (231.4 MUm) to supine (203.9
MUm). There were no significant hemodynamic changes. CONCLUSION: We demonstrated
that choroidal thickness increased in response to increased perfusion pressures
in patients with CSC and not in normal controls. These findings likely represent
an autonomic dysregulation of choroidal blood flow in patients with CSC.
PMID- 28489694
TI - EFFICACY OF INTRAVITREAL RANIBIZUMAB INJECTIONS IN THE TREATMENT OF VITREOUS
HEMORRHAGE RELATED TO PROLIFERATIVE DIABETIC RETINOPATHY.
AB - PURPOSE: To investigate the efficacy of intravitreal ranibizumab injections in
proliferative diabetic retinopathy associated with vitreous hemorrhage (VH).
METHODS: A prospective study including patients with proliferative diabetic
retinopathy who presented with persistent VH. Vitreous hemorrhage was graded into
mild, moderate, and severe. Patients were randomized into two groups: the
ranibizumab group was treated with intravitreal injections of ranibizumab and the
control group was assigned to observation alone. Vitrectomy was performed if
there was any aggravation of the VH in patients with mild, moderate, and severe
VH or in the absence of improvement by 16 weeks in patients with moderate and
severe VH. RESULTS: The ranibizumab group included 71 patients and the control
group included 62 patients. There was a statistically significant difference in
the vitrectomy rate in patients with mild-to-moderate VH (5 patients [7.04%] and
12 patients [19.35%], respectively; P = 0.04). However, there was no
statistically significant difference in the overall vitrectomy rate, and in the
vitrectomy rate in severe VH (17 [23.94%] and 12 [16.90%] patients in the
ranibizumab group vs. 22 [35.48%] and 10 [16.13%] patients in the control group,
P = 0.14 and P = 0.83, respectively). Recurrence of the VH occurred in 22
patients in the ranibizumab group and 29 patients in the control group (P =
0.06). Better visual acuity measurements were recorded on all follow-up visits in
the ranibizumab group (P <= 0.04). CONCLUSION: Intravitreal ranibizumab
injections could be considered in proliferative diabetic retinopathy patients
with mild and moderate VH.
PMID- 28489695
TI - CLASSIFICATION OF HALLER VESSEL ARRANGEMENTS IN ACUTE AND CHRONIC CENTRAL SEROUS
CHORIORETINOPATHY IMAGED WITH EN FACE OPTICAL COHERENCE TOMOGRAPHY.
AB - PURPOSE: To compare the prevailing patterns of Haller vessel arrangements at the
posterior pole between healthy eyes and those with central serous
chorioretinopathy (CSC) using en face optical coherence tomography. METHODS: Eyes
of normal subjects and patients with acute or chronic CSC underwent optical
coherence tomography imaging (RTVue 100; Optovue Inc, Fremont, CA). En face
sections at the level of the Haller layer were classified by two masked graders
into five mutually exclusive morphologic categories (temporal herringbone,
branched from below, laterally diagonal, double arcuate, and reticular). The
relative prevalence of each Haller vessel arrangement pattern was determined for
each phenotype. RESULTS: Numbers of eyes examined were as follows: 154 eyes of 77
normal subjects; 41 eyes of 31 patients with acute CSC; and 39 eyes of 33
patients with chronic CSC. The mean age of participants was 44.4 +/- 14.6 years
for healthy subjects (M:F = 37:40), 48.5 +/- 8.2 years (M:F = 24:7) for acute
CSC, and 65.3 +/- 13.1 years (M:F = 28:5) for chronic CSC. The relative
prevalence of each Haller vessel arrangement pattern differed by phenotype. The
temporal herringbone pattern was most prevalent in healthy eyes (49.2%), whereas
a reticular pattern was most prevalent in eyes with acute and/or chronic CSC
(combined, 48.8%). CONCLUSION: A significant difference was observed in the
prevalence of respective Haller vessel arrangement patterns between eyes of
normal subjects and those of patients with either acute or chronic CSC. Although
further study is needed to determine the mechanistic factors underlying these
differences, and the hemodynamic implications, our data suggest that en face
optical coherence tomography may find a formal role in choroidal disease
classification.
PMID- 28489696
TI - PREDICTORS OF REFRACTORY MACULAR EDEMA AFTER BRANCH RETINAL VEIN OCCLUSION
FOLLOWING INTRAVITREAL BEVACIZUMAB.
AB - PURPOSE: To evaluate the predictors of refractory macular edema (ME) that
develops despite multiple bevacizumab injections in patients with branch retinal
vein occlusion (BRVO). METHODS: A total of 107 patients who followed at least 2
years were assigned to 2 groups: a refractory group (n = 56) and a responsive
group (n = 51). Baseline characteristics, treatment response at 3 months, and
fluorescein angiographic findings at 6 months were compared. Then we tried to
identify factors associated with refractory ME development. RESULTS: Compared to
the responsive group, the refractory group had older age, longer pre-treatment
duration, and shorter occlusion distance from disk. At 3 months, the refractory
group exhibited lower visual acuity, thicker central retinal thickness (CRT), and
larger proportion of external limiting membrane (ELM) and outer plexiform layer
disruption. After 6 months, proportion of unresolved vein occlusion, macular
ischemia, number of microaneurysms, and non-perfusion areas were higher in the
refractory group. Refractory ME was associated with pre-treatment duration >=3
months, short occlusion distance from disk, thick CRT and ELM disruption at 3
months, and unresolved vein occlusion at 6 months. CONCLUSION: If BRVO-ME
patients exhibit the above-mentioned characteristics, they may have refractory
ME, which should inform treatment decisions.
PMID- 28489697
TI - Validating the Quality of Life After Brain Injury Through Rasch Analysis.
AB - OBJECTIVE: The Quality of Life after Brain Injury (QOLIBRI), a cross-cultural
instrument, has been validated in several languages; however, traditional
psychometric approaches have critical limitations. Therefore, we applied the
Rasch model for validating the 37-item QOLIBRI scale among a Chinese population
with traumatic brain injury. PARTICIPANTS AND SETTING: In total, 587 participants
(mean age: 44.2 +/- 15.4 years; women, 46.3%) were surveyed in neurosurgery
departments at 6 hospitals in Taipei, Taiwan. MAIN OUTCOME MEASURE: The QOLIBRI.
RESULTS: Of the 6 subscales of the QOLIBRI, 4 (cognition, self, daily life and
autonomy, and social relationships) were unidimensional, valid, and reliable,
whereas the remaining 2 (emotions and physical problems) exhibited poor
unidimensionality, item and person reliability, and person-item targeting. Five
items (energy, concentrating, getting out and about, sex life, and achievements)
showed considerable differential item functioning among age groups, disability
levels, and time since traumatic brain injury. CONCLUSION: According to item
response theory, we identified psychometric issues in the emotions and physical
problems subscales of the QOLIBRI as well as several differential item
functioning items. Future research is required to determine whether similar
results are observed in other language versions of the QOLIBRI or in other
countries.
PMID- 28489698
TI - Epidemiology of Isolated Versus Nonisolated Mild Traumatic Brain Injury Treated
in Emergency Departments in the United States, 2006-2012: Sociodemographic
Characteristics.
AB - OBJECTIVES: To describe the frequencies and rates of mild traumatic brain injury
(mTBI) emergency department (ED) visits, analyze the trend across the years, and
compare sociodemographic characteristics of visits by mTBI type (ie, mTBI as the
only injury, or present along with other injuries). DESIGN: Population-based
descriptive study using data from the Nationwide Emergency Department Sample
(2006-2012). METHODS: Joinpoint regression was used to calculate the average
annual percent changes of mTBI incidence rates. Characteristics between isolated
and nonisolated visits were compared, and the odds ratios were reported. RESULTS:
The rate per 100 000 population of mTBI ED visits in the United States increased
significantly from 569.4 (in 2006) to 807.9 (in 2012). The highest rates were
observed in 0- to 4-year-olds, followed by male 15- to 24-year-olds and females
65 years and older; the lowest rates were among 45- to 64-year-olds. The majority
(70%) of all visits were nonisolated and occurred more frequently in residents of
metropolitan areas. Falls were the leading external cause. Most visits were
privately insured or covered by Medicare/Medicaid, and the injury occurred on
weekdays in predominantly metropolitan hospitals in the South region.
CONCLUSIONS: The burden of mTBI in US EDs is high. Most mTBI ED visits present
with other injuries. Awareness of sociodemographic factors associated with
nonisolated mTBI may help improve diagnosis in US EDs. This information has
implications for resource planning and mTBI screening in EDs.
PMID- 28489699
TI - Incidence and Associated Risk Factors of Traumatic Brain Injury in a Cohort of
Homeless and Vulnerably Housed Adults in 3 Canadian Cities.
AB - OBJECTIVE: To examine the factors associated with incident traumatic brain injury
(TBI) among homeless and vulnerably housed persons over a 3-year follow-up
period. SETTING AND PARTICIPANTS: Data were obtained from the Health and Housing
in Transition study, which tracked the health and housing status of 1190 homeless
or vulnerably housed individuals in 3 Canadian cities for 3 years. DESIGN AND
MAIN MEASURES: Main measure was self-reported incident TBI during the follow-up
period. Factors associated with TBI were ascertained using mixed-effects logistic
regression. RESULTS: During first, second, and third years of follow-up, 187
(19.4%), 166 (17.1%), and 172 (17.9%) participants reported a minimum of 1
incident TBI, respectively. Among 825 participants with available data for all 3
years of follow-up, 307 (37.2%) reported at least 1 incident TBI during the 3
year follow-up period. Lifetime prevalence of TBI, endorsing a history of mental
health diagnoses at baseline, problematic alcohol and drug use, younger age,
poorer mental health, and residential instability were associated with increased
risk of incident TBI during follow-up period. CONCLUSION: Mental health support
and addressing residential instability and problematic substance use may reduce
further risk of TBI and its associated poor health and social outcomes in this
population.
PMID- 28489700
TI - P300 Event-Related Potentials Differentiate Better Performing Individuals With
Traumatic Brain Injury: A Preliminary Study of Semantic Processing.
AB - OBJECTIVE: To measure the effect of traumatic brain injury on the cognitive
processing of words, as measured by the P300, in a semantic categorization task.
PARTICIPANTS: Eight adults with a history of moderate to severe traumatic brain
injury and 8 age- and gender-matched controls. DESIGN: A pilot study measuring
cognitive event-related potentials in response to word pairs that were either in
same or different semantic categories. MAIN MEASURES: The P300 (P3b) component of
the auditory event-related potential and neuropsychological assessment. RESULTS:
Two patterns of P300 amplitude related to brain injury were observed.
Participants with poorer performance on neuropsychological tests exhibited
reduced P300 amplitude as compared to controls but showed the typical P300
parietal scalp distribution. In contrast, better performing participants
demonstrated robust P300 amplitude but a substantially altered scalp
distribution, characterized by the recruitment of anterior brain regions in
addition to parietal activation. CONCLUSIONS: The recruitment of frontal areas
after traumatic brain injury may represent compensatory neural mechanisms
utilized to successfully maximize task performance. The P300 in a semantic
processing paradigm may be a sensitive marker of neural plasticity that could be
used to improve functional outcomes in cognitive remediation paradigms.
PMID- 28489701
TI - Pediatricians' Knowledge, Attitudes, and Behaviors to Screening Children After
Complicated Mild TBI: A Survey.
AB - OBJECTIVE: To understand pediatricians' attitudes, knowledge, and behaviors about
the care of children with complicated mild traumatic brain injury (TBI).
PARTICIPANTS: A total of 3500 pediatricians randomly selected from the American
Medical Association Master File. DESIGN: It was a cross-sectional survey. MAIN
MEASURES: A survey developed to assess pediatricians' attitudes toward following
children with complicated mild TBI for cognitive and behavioral sequelae; their
knowledge of TBI sequelae; and their usual evaluation and management of children
after TBI. RESULTS: There were 576 (16.5%) completed responses. Most
pediatricians (51%) see 1 or 2 patients with complicated mild TBI annually. Most
do not think that pediatricians are the correct clinician group to be primarily
responsible for following children with complicated mild TBI for cognitive (74%)
or behavioral sequelae (54%). Pediatricians report difficulty referring children
for cognitive (56%) and behavioral (48%) specialty services. Pediatricians have
good knowledge of short-term complications of complicated mild TBI. CONCLUSION:
Pediatricians do not think they are the clinicians that should primarily care for
children after hospitalization for complicated mild TBI; however, other
clinicians are frequently not accessible. Pediatricians need educational and
referral support to provide surveillance for injury sequelae in this group of
children.
PMID- 28489703
TI - A Survey of Clinicians Working in Brain Injury Rehabilitation: Are Social
Cognition Impairments on the Radar?
AB - OBJECTIVES: To examine the social cognition assessment practices of clinicians
working with children and adults with traumatic brain injury. MAIN MEASURES:
Online survey addressing frequency of social cognition impairments, how these are
assessed and obstacles to same, and treatment practices. PARTICIPANTS: A total of
443 clinicians worldwide working in inpatient and outpatient settings. RESULTS:
While 84% of clinicians reported that more than half of their clients with severe
traumatic brain injury had social cognition impairments, 78% of these reported
that they infrequently or never assessed these domains using a formal assessment
tool. Lack of reliable tests was most frequently (33% of respondents) cited as
the greatest barrier to undertaking social cognition assessment. CONCLUSIONS AND
IMPLICATIONS: Improvements are needed in the development and norming of
instruments capable of detecting social cognition impairments in the traumatic
brain injury population. Additional training and education is needed in the use
of social cognition assessment tools.
PMID- 28489702
TI - The Minimal Clinically Important Difference for the Mayo-Portland Adaptability
Inventory.
AB - OBJECTIVES: To determine the Minimal Clinically Important Difference (MCID) and
Robust Clinically Important Difference (RCID) of the Mayo-Portland Adaptability
Inventory-4 (MPAI-4) as measures of response to intervention. METHODS:
Retrospective analysis of existing data. Both distribution- and anchor-based
methods were used to triangulate on the MCID and to identify a moderate, that is,
more robust, level of change (RCID) for the MPAI-4. These were further evaluated
with respect to clinical provider ratings. PARTICIPANTS: Data for individuals
with acquired brain injury in rehabilitation programs throughout the United
States in the OutcomeInfo Database (n = 3087) with 2 MPAI-4 ratings. MAIN
MEASURES: MPAI-4, Supervision Rating Scale, Clinician Rating of Global Clinical
Improvement. RESULTS: Initial analyses suggested 5 T-score points (5T) as the
MCID and 9T as the RCID. Eighty-one percent to 87% of clinical raters considered
a 5T change and 99% considered a 9T change to indicate meaningful improvement.
CONCLUSIONS: 5T represents the MCID for the MPAI-4 and 9T, the RCID. Both values
are notably less than the Reliable Change Index (RCI). While the RCI indicates
change with a high level of statistical confidence, it may be insensitive to
change that is considered meaningful by providers and participants as indicated
by the MCID.
PMID- 28489704
TI - Factors Associated With Rehabilitation Outcomes After Traumatic Brain Injury:
Comparing Functional Outcomes Between TBIMS Centers Using Hierarchical Linear
Modeling.
AB - OBJECTIVE: To examine differences in patient outcomes across Traumatic Brain
Injury Model Systems (TBIMS) rehabilitation centers and factors that influence
these differences using hierarchical linear modeling (HLM). SETTING: Sixteen
TBIMS centers. PARTICIPANTS: A total of 2056 individuals 16 years or older with
moderate to severe traumatic brain injury (TBI) who received inpatient
rehabilitation. DESIGN: Multicenter observational cohort study using HLM to
analyze prospectively collected data. MAIN OUTCOME MEASURES: Functional
Independence Measure and Disability Rating Scale total scores at discharge and 1
year post-TBI. RESULTS: Duration of posttraumatic amnesia (PTA) demonstrated a
significant inverse relationship with functional outcomes. However, the magnitude
of this relationship (change in functional status for each additional day in PTA)
varied among centers. Functional status at discharge from rehabilitation and at 1
year post-TBI could be predicted using the slope and intercept of each TBIMS
center for the duration of PTA, by comparing it against the average slope and
intercept. CONCLUSIONS: HLM demonstrated center effect due to variability in the
relationship between PTA and functional outcomes of patients. This variability is
not accounted for in traditional linear regression modeling. Future studies
examining variations in patient outcomes between centers should utilize HLM to
measure the impact of additional factors that influence patient rehabilitation
functional outcomes.
PMID- 28489705
TI - RETINAL AND CHOROIDAL VASCULAR OCCLUSION FOLLOWING AQUEOUS MISDIRECTION SYNDROME
IN A PATIENT WITH SICKLE CELL TRAIT.
AB - PURPOSE: To report a patient with retinal and choroidal vascular occlusion as a
presenting sign of sickle cell trait following the development of aqueous
misdirection syndrome. METHODS: Retrospective chart review. RESULTS: A patient
treated for bilateral chronic angle-closure glaucoma with sequential EX-PRESS
glaucoma filtration device surgery developed sequential bilateral aqueous
misdirection syndrome. The left eye developed retinal arterial and localized
choroidal vascular occlusions subsequent to an acute elevation in intraocular
pressure and possibly the use of oral acetazolamide. The patient was subsequently
found to have sickle cell trait. The right eye developed aqueous misdirection
with acute elevation of intraocular pressure as well, but the patient was not
treated with oral acetazolamide and did not develop vascular occlusion.
CONCLUSION: Retinal and choroidal vascular occlusions can be the presenting sign
of a patient with sickle cell trait. Sickle cell screening may be beneficial in
African American or Middle Eastern patients after an acute rise in intraocular
pressure, particularly before initiation of treatment with oral carbonic
anhydrase inhibitors.
PMID- 28489706
TI - OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF CONGENITAL SIMPLE HAMARTOMA OF THE
RETINAL PIGMENT EPITHELIUM.
AB - PURPOSE: To describe the optical coherence tomography angiography features of
congenital simple hamartoma of the retinal pigment epithelium. METHODS: Case
report. RESULTS: A 14-year-old boy was referred for an asymptomatic fundus tumor
in the left eye. Visual acuity was 20/20 in the right eye and 20/40 in the left
eye. The right fundus was normal. The left fundus disclosed a gray-white nodular
retinal mass of 2-mm diameter in the juxtafoveal region, protruding into the
vitreous cavity and causing radial retinal folds. The mass demonstrated
echodensity without calcification on ultrasonography, hypoautofluorescence on
short-wavelength autofluorescence, and mixed hyporeflective and hyperreflective
areas on near-infrared reflectance imaging. By fluorescein angiography, the mass
showed absolute hypofluorescence through the arteriovenous phase and diffuse late
hyperfluorescence and staining. Optical coherence tomography revealed an
optically dense lesion with abrupt posterior shadowing, whereas optical coherence
tomography angiography showed an extensive haphazard intratumoral vascular
network with fairly large-caliber (100-200 microns) vessels occupying full
thickness tumor, demonstrating more vascular details than visualized on
fluorescein angiography. Serial segmental evaluation of the optical coherence
tomography angiography en face images confirmed an intratumoral vascular network
for full tumor depth down to retinal pigment epithelium, not related to
projection artifact. Final diagnosis was congenital simple hamartoma of the
retinal pigment epithelium. Considering the benign tumor, observation was
recommended. CONCLUSION: Optical coherence tomography angiography of congenital
simple hamartoma of the retinal pigment epithelium revealed an extensive
intratumoral, haphazard, large-caliber vascular network, more evident than seen
on fluorescein angiography. Optical coherence tomography angiography has added
new insight into this rare tumor.
PMID- 28489707
TI - INTRAVITREAL DEXAMETHASONE (OZURDEX) IMPLANT FOR RADIATION MACULOPATHY SECONDARY
TO STEREOTACTIC RADIOTHERAPY FOR POSTERIOR UVEAL MELANOMA.
AB - PURPOSE: To evaluate the efficacy of 0.7 mg intravitreal dexamethasone implant in
the treatment of radiation maculopathy after stereotactic radiotherapy for
posterior uveal melanoma. METHODS: Retrospective chart review of seven eyes of
seven consecutive patients was performed. Extracted data included age, sex,
initial and follow-up visual acuities and central macular thickness values,
intraocular pressure, follow-up time, number of implants, and time elapsed from
radiotherapy to implantation. Main outcome measures were visual acuity and
central macular thickness. Glaucoma, cataract formation, or systemic side
effects, if any, were recorded. RESULTS: Female to male ratio was 4:3. Mean age
was 49.9 +/- 17.0 (range: 27-73). Initial mean visual acuity was 20.4 +/- 12.5
Early Treatment Diabetic Retinopathy Study letters and initial central macular
thickness measured 514.1 +/- 135.1 MUm on spectral domain optical coherence
tomography. All patients except one showed improvement in visual acuity and a
mean improvement of 7.4 +/- 6.2 letters was observed in the whole group (range: 0
16). The mean reduction in central macular thickness was 226.7 +/- 157.0 MUm
after a mean 9.1 +/- 3.4 months of follow-up. On average, implantation of
intravitreal dexamethasone was performed 35.2 +/- 16.5 months after radiotherapy.
Four patients were treatment naive and three had previous intravitreal
bevacizumab injections with limited response. Ozurdex reimplantations were
performed in four patients and the mean number of injections was 1.7 +/- 0.8.
Mean time to reimplantation was 5.0 +/- 2.12 months. Only one patient developed
posterior subcapsular cataract and all patients had intraocular pressures within
normal limits. No systemic side effects were observed. CONCLUSION: In our
experience, intravitreal implantation of 0.7 mg dexamethasone is an anatomically,
and to a lesser extent functionally effective procedure for radiation maculopathy
after stereotactic radiotherapy for posterior uveal melanoma.
PMID- 28489708
TI - MUC1, MUC5AC, and MUC6 polymorphisms, Helicobacter pylori infection, and gastric
cancer: a systematic review and meta-analysis.
AB - The risk of Helicobacter pylori (HP) infection, as well as gastric cancer (GC),
in association with genetic polymorphisms of gene encoding for mucins, has been
investigated with contradictory results. We carried out this systematic review
and meta-analysis to summarize the relationship between MUC1, MUC5AC, and MUC6
polymorphisms and HP infection, as well as GC risk. We searched MEDLINE, ISI Web
of Science, Scopus bibliographic databases and the HuGE Navigator database. Odds
ratios (ORs) and 95% confidence interval (CI) were calculated to assess the
association between the genetic polymorphisms, and HP/GC risk. A random-effect
model was used to calculate the pooled ORs, overall and by ethnicity. Twenty-one
studies were included, of which five on HP and 18 on GC, of which two were in
common. The meta-analysis of 10 studies on the MUC1 rs4072037 polymorphism and GC
risk reported an OR of 0.66 (95% CI: 0.57-0.78) for the dominant model (AG/GG vs.
AA). When stratifying for ethnicity, an OR of 0.73 (95% CI: 0.62-0.86) was
reported for the Asian population and an OR of 0.48 (95% CI: 0.38-0.61) was
reported for the White population. Our study confirms the protective effect of
MUC1 rs4072037 polymorphism on the risk of GC under the dominant model. Further
studies reporting information on HP status in cases and controls would be
required to evaluate whether the protective effect of MUC1 protein might be
attributable to a protective effect towards the HP infection, or through
different mechanisms.
PMID- 28489709
TI - Your Academy: Opportunities and Challenges.
PMID- 28489710
TI - Survival Guide for the Orthopaedic Surgery Match.
AB - The process of matching into an orthopaedic surgery residency program can be
daunting for medical students. Rumors, innuendo, urban myths, and electronic
misinformation can accentuate the angst experienced by students both domestically
and internationally. This article dispels myths and presents an up-to-date,
evidence-based (where possible), and experience-laden road map to assist medical
students interested in pursuing a career in orthopaedic surgery. Our framework
takes into account the program selection, test scores, letters of recommendation,
visiting rotations, interviews, and communication. We hope that this survival
guide will serve as a reference point assisting medical students in achieving
successful matches into orthopaedic surgery residency programs.
PMID- 28489711
TI - Resident Selection Beyond the United States Medical Licensing Examination.
AB - The resident application process has matured over the decades to become an
efficient system. An unforeseen consequence of this efficiency is the massive
number of applications that each orthopaedic surgery residency program must sort
through to arrive at a manageable rank list. The most widely used filter in
today's application cycle is an applicant's performance on the United States
Medical Licensing Examination Step 1. Although no evidence exists to prove that
this examination is predictive of any of the potentially defining characteristics
of a successful resident, orthopaedic surgery programs historically have had few
alternative options. A growing body of literature suggests that a more focused
investigation of an applicant's inherent personality traits, as evidenced by his
or her past accomplishments, as well as a structured use of questionnaires as
part of the application process may improve the ability of orthopaedic surgery
residency programs to predict who will be a successful resident.
PMID- 28489712
TI - Maximizing Surgical Skills During Fellowship Training.
AB - Orthopaedic surgery fellowship provides an opportunity to further develop skills
in a particular subspecialty. However, the condensed time frame, complex skill
acquisition, and clinical demands require efficient and effective learning
techniques to achieve mastery. As with any advanced task, success during
fellowship training can be achieved with active participation and a goal-directed
approach. Skill acquisition can be successfully achieved by following a framework
that includes preparation, execution, and reflection for every surgical case.
PMID- 28489713
TI - Denervation of the Wrist Joint for the Management of Chronic Pain.
AB - Wrist denervation for the management of chronic wrist pain is a safe and
effective procedure that can delay or eliminate the need for more invasive and
kinematically compromising salvage procedures. Wrist denervation has become
increasingly popular since it was first described in 1959, and the technique has
evolved from more extensive denervations to limited single-incision approaches.
Many physicians have performed this procedure as a palliative approach to
managing chronic wrist pain and as an adjunct to other procedures.
PMID- 28489714
TI - Feasibility of and Rationale for the Collection of Orthopaedic Trauma Surgery
Quality of Care Metrics.
AB - INTRODUCTION: Reproducible metrics are needed to evaluate the delivery of
orthopaedic trauma care, national care, norms, and outliers. The American College
of Surgeons (ACS) is uniquely positioned to collect and evaluate the data needed
to evaluate orthopaedic trauma care via the Committee on Trauma and the Trauma
Quality Improvement Project. METHODS: We evaluated the first quality metrics the
ACS has collected for orthopaedic trauma surgery to determine whether these
metrics can be appropriately collected with accuracy and completeness. The
metrics include the time to administration of the first dose of antibiotics for
open fractures, the time to surgical irrigation and debridement of open tibial
fractures, and the percentage of patients who undergo stabilization of femoral
fractures at trauma centers nationwide. These metrics were analyzed to evaluate
for variances in the delivery of orthopaedic care across the country. RESULTS:
The data showed wide variances for all metrics, and many centers had incomplete
ability to collect the orthopaedic trauma care metrics. There was a large
variability in the results of the metrics collected among different trauma center
levels, as well as among centers of a particular level. DISCUSSION: The ACS has
successfully begun tracking orthopaedic trauma care performance measures, which
will help inform reevaluation of the goals and continued work on data collection
and improvement of patient care. Future areas of research may link these
performance measures with patient outcomes, such as long-term tracking, to assess
nonunion and function. This information can provide insight into center
performance and its effect on patient outcomes. CONCLUSIONS: The ACS was able to
successfully collect and evaluate the data for three metrics used to assess the
quality of orthopaedic trauma care. However, additional research is needed to
determine whether these metrics are suitable for evaluating orthopaedic trauma
care and cutoff values for each metric.
PMID- 28489715
TI - Assessment of Malpractice Claims Associated With Acute Compartment Syndrome.
AB - BACKGROUND: Because acute compartment syndrome is one of the few limb-threatening
and life-threatening orthopaedic conditions and is difficult to diagnose, it is a
frequent source of litigation. Understanding the factors that lead to plaintiff
verdicts and higher indemnity payments may improve patient care by identifying
common pitfalls. METHODS: The VerdictSearch legal claims database was queried for
the term "compartment syndrome." After 46 cases were excluded for missing
information or irrelevancy, 139 cases were reviewed. The effects of plaintiff
demographics, mechanism of injury, and complications were assessed. RESULTS: Of
139 cases, 37 (27%) were settled, 69 (50%) resulted in a defendant ruling, and 33
(24%) resulted in a plaintiff ruling. Juries were more likely to rule in favor of
juvenile plaintiffs than adult patients (P = 0.002) and female plaintiffs than
male plaintiffs (P = 0.008), but indemnity payments were not affected by the age
or sex of the plaintiff. Plaintiffs who experienced acute compartment syndrome as
a complication of surgery were more likely to win their suit and receive higher
awards (P < 0.05), compared with those in whom the condition developed as a
result of trauma. Amputation or delay in diagnosis or treatment did not affect
plaintiff verdicts or awards. CONCLUSION: Defendants were more likely to lose a
lawsuit concerning the management of acute compartment syndrome if the patient
was a woman or child or if acute compartment syndrome developed as a complication
of a surgical procedure.
PMID- 28489716
TI - The Medicare Access and CHIP Reauthorization Act (MACRA) of 2015: What's New?
AB - The Centers for Medicare and Medicaid Services (CMS) released its Final Rule on
the Medicare Access and CHIP [Children's Health Insurance Program]
Reauthorization Act (MACRA) in November 2016. The Rule finalizes the details of
the merit-based incentive payment system (MIPS) and the alternative payment model
(APM), which will now collectively be referred to as the Quality Payment Program
(QPP). This article offers the orthopaedic community a summary of the alterations
in healthcare policy that will affect practices nationwide.
PMID- 28489718
TI - Early Life Origins of Hearing Impairment in Older People.
PMID- 28489717
TI - Coliphages and Gastrointestinal Illness in Recreational Waters: Pooled Analysis
of Six Coastal Beach Cohorts.
AB - BACKGROUND: Coliphages have been proposed as indicators of fecal contamination in
recreational waters because they better mimic the persistence of pathogenic
viruses in the environment and wastewater treatment than fecal indicator
bacteria. We estimated the association between coliphages and gastrointestinal
illness and compared it with the association with culturable enterococci.
METHODS: We pooled data from six prospective cohort studies that enrolled coastal
beachgoers in California, Alabama, and Rhode Island. Water samples were collected
and gastrointestinal illness within 10 days of the beach visit was recorded.
Samples were tested for enterococci and male-specific and somatic coliphages. We
estimated cumulative incidence ratios (CIR) for the association between swimming
in water with detectable coliphage and gastrointestinal illness when human fecal
pollution was likely present, not likely present, and under all conditions
combined. The reference group was unexposed swimmers. We defined continuous and
threshold-based exposures (coliphage present/absent, enterococci >35 vs. <=35
CFU/100 ml). RESULTS: Under all conditions combined, there was no association
between gastrointestinal illness and swimming in water with detectable coliphage
or enterococci. When human fecal pollution was likely present, coliphage and
enterococci were associated with increased gastrointestinal illness, and there
was an association between male-specific coliphage level and illness that was
somewhat stronger than the association between enterococci and illness. There
were no substantial differences between male-specific and somatic coliphage.
CONCLUSIONS: Somatic coliphage and enterococci had similar associations with
gastrointestinal illness; there was some evidence that male-specific coliphage
had a stronger association with illness than enterococci in marine waters with
human fecal contamination.
PMID- 28489719
TI - Microkeratome-Assisted Anterior Lamellar Keratoplasty for the Correction of High
Degree Postkeratoplasty Astigmatism.
AB - PURPOSE: To describe the surgical technique and report the outcomes of patients
treated with microkeratome-assisted anterior lamellar keratoplasty (MALK) for the
correction of high-degree postkeratoplasty astigmatism. METHODS: Four eyes of 2
patients with extremely high (>10 D) and irregular [surface asymmetry index >1.0
D] post-penetrating keratoplasty astigmatism occurring after complete suture
removal underwent MALK and were followed for at least 3 years after the
procedure. In all cases, 250-um lamellar keratectomy was performed, followed by 2
full-thickness incisions through the penetrating keratoplasty scar and the
placement of an appropriately sized donor graft, which was secured with a double
running 10-0 nylon suture. All sutures were removed in all eyes within 1 year
from surgery. Corrected distance visual acuity, refraction, corneal topography,
and endothelial cell density were noted at each examination. RESULTS: At the last
follow-up examination (3 years or longer after MALK), corrected distance visual
acuity had improved to 20/20, refractive astigmatism had decreased to an average
of 2.1 D (in all cases within 4.5 D), and the average surface asymmetry index had
reduced from 2.27 to 0.56. CONCLUSIONS: MALK is an effective and safe technique
for the correction of high-degree postkeratoplasty astigmatism.
PMID- 28489720
TI - Expression of Peroxiredoxin 2 and Vascular Endothelial Growth Factor Receptor 2
in Pterygium.
AB - PURPOSE: The expression of peroxiredoxin 2 and vascular endothelial growth factor
receptor 2 (VEGFR2) was detected in pterygium to investigate whether they are
involved in the pathogenesis or recurrence of pterygium and to evaluate the
association between peroxiredoxin 2 and VEGFR2 in pterygium. METHODS: Ten normal
bulbar conjunctivae, 35 primary pterygia, and 35 recurrent pterygia were
obtained. Formalin-fixed, paraffin-wax-embedded tissues were analyzed by
immunohistochemistry with peroxiredoxin 2 and VEGFR2 antibodies. RESULTS: There
was no statistical difference between primary pterygia and recurrent pterygia in
terms of age and sex (P = 0.685; P = 0.811). The expression rate of peroxiredoxin
2 (94.3%, 66/70) and VEGFR2 (61.4%, 43/70) was increased in pterygia compared
with normal conjunctivae (negative). The expression of peroxiredoxin 2 in
recurrent pterygia (negative 0, weak 0, moderate 27, strong 8) was higher than
that in primary pterygia (negative 6, weak 16, moderate 13, strong 0) (P <
0.001). The expression of VEGFR2 in recurrent pterygia (negative 4, weak 5,
moderate 12, strong 4) was higher than that in primary pterygia (negative 23,
weak 10, moderate 1, strong 1) (P < 0.001). The expression of peroxiredoxin 2 was
consistent with that of VEGFR2 in pterygium (r = 0.348, P = 0.006). CONCLUSIONS:
Overexpression of peroxiredoxin 2 and VEGFR2 in pterygium might be involved in
the pathogenesis or recurrence of pterygium. The increase of VEGFR2 might be
related to the increase of peroxiredoxin 2 in response to excessive reactive
oxygen species from ultraviolet exposure.
PMID- 28489721
TI - Tear Cytokine Levels in Contact Lens Wearers With Acanthamoeba Keratitis.
AB - PURPOSE: To determine differences in key tear film cytokines between mild and
severe cases of acanthamoeba keratitis (AK) and control contact lens (CL)
wearers. METHODS: This was a prospective study of CL wearers with AK attending
Moorfields Eye Hospital and control CL wearers from the Institute of Optometry,
London. Basal tear specimens were collected by 10-MUL capillary tubes (BLAUBRAND
intraMark, Wertheim, Germany), and tear protein levels were measured with a
multiplex magnetic bead array (Luminex 100; Luminex Corporation, Austin, TX) for
cytokines interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-17A, IL-17E, IL-17F, IL
22, and interferon gamma and with enzyme-linked immunosorbent assay (Abcam,
Cambridge, United Kingdom) for CXCL2. Severe cases of AK were defined as having
active infection for over 12 months and at least 1 severe inflammatory event.
RESULTS: One hundred and thirty-two tear samples were collected from a total of
61 cases (15 severe and 46 mild-moderate) and 22 controls. IL-8, part of the Toll
like receptor 4 cytokine cascade, was found to be expressed at a detectable level
more often in cases of AK than in control CL wearers (P = 0.003) and in higher
concentrations in severe cases than in milder forms of the disease (z = -2.35).
IL-22, part of the IL-10 family, and a proinflammatory Th17 cytokine, was
detected more often in severe cases than in milder forms of AK (P < 0.02).
CONCLUSIONS: Profiling patients with AK during disease shows differences in
cytokine levels between severe and milder disease that may inform clinical
management. The Toll-like receptor 4 and IL-10/Th17 inflammatory pathways should
be included in further investigations of this disease.
PMID- 28489722
TI - Bilateral Herpetic Keratitis After Bilateral Intravitreal Bevacizumab for
Exudative Macular Degeneration.
AB - PURPOSE: To report a case of bilateral herpetic epithelial keratitis after
bilateral intravitreal bevacizumab injections for the treatment of exudative age
related macular degeneration. METHODS: A 66-year-old man with diabetes and an
extensive history of bilateral anti-vascular endothelial growth factor treatments
for exudative age-related macular degeneration received an intravitreal
bevacizumab injection in the right eye and triple therapy (bevacizumab,
photodynamic therapy, and triamcinolone acetonide) in the left eye. After 4 days,
he presented with pain, photophobia, tearing, and decreased vision in both eyes.
Slit-lamp examination revealed bilateral dendritic epithelial lesions with
terminal bulbs, and he was diagnosed with bilateral herpes simplex epithelial
keratitis. RESULTS: The patient was treated with ganciclovir ophthalmic ointment
and oral acyclovir with resolution of signs and symptoms. CONCLUSIONS: To our
knowledge, this is the first documented account of bilateral herpetic epithelial
keratitis after bilateral intravitreal bevacizumab injections.
PMID- 28489723
TI - Femtosecond Laser Assisted Pterygium Surgery.
AB - PURPOSE: Pterygium is a prevalent ocular surface disorder. Conjunctival
autografting (CAG) after pterygium resection is the gold standard treatment.
Thinner CAGs without Tenon tissue provide better results but are technically
difficult to achieve. We report on the first femtosecond laser (FSL)-assisted
pterygium surgery (FLAPS) in humans. METHODS: In a clinical trial, we treated 6
eyes of 5 patients with FLAPS. After manual removal of the pterygium, CAGs were
dissected with the Ziemer Z8 at 60-MUm depth and glued into the resection defect.
CAG thickness and diameter were measured. RESULTS: The CAG area measured 17.9%
smaller than the laser settings (P = 0.03). Central (75.6 +/- 13.7 MUm) and
peripheral (77.7 +/- 13.2 MUm) CAG thickness did not differ significantly (P =
0.3). No buttonholes or CAG tags occurred. The mean dissection time was 19.5 +/-
1.2 seconds, and the time to remove the FSL-prepared CAG and to unfold it onto
the cornea was 10.3 +/- 3.8 seconds. During 35.8 +/- 38.0 days of follow-up, no
postoperative complication or recurrences occurred. The conjunctival epithelium
had healed at the CAG resection site within 1 week with no evidence of scarring.
CONCLUSIONS: FLAPS is a new technique, in which the preparation of an ultrathin
CAG is done by the FSL. After optimization in porcine eyes, the clinical trial in
the first 6 eyes was performed without any complications and the FSL might assist
in further standardizing the surgical procedure. Longer follow-up and larger
cohorts are needed to assess recurrence rates.
PMID- 28489724
TI - Social Support, Unstable Angina, and Stroke as Predictors of Depression in
Patients With Coronary Heart Disease.
AB - BACKGROUND: Depression is known to adversely affect coronary heart disease
patients in western countries; however, no study of social support and depression
has been conducted in the Chinese population. OBJECTIVE: The aim of this study
was to investigate the predictors of depression in patients with coronary heart
disease. METHODS: Between January and December 2015, a cross-sectional sample of
105 Taiwanese patients from cardiology units completed a demographic and clinical
characteristics questionnaire, Enhancing Recovery in Coronary Heart Disease
Social Support Inventory, and Patient Health Questionnaire-9. RESULTS: Thirty
nine percent of the participants reported low social support, and 61.0% had
depression symptoms. Eight factors predicted depression. Social support was
significantly and adversely correlated with depression (r = -.481, P < .01). The
other 7 factors were positively correlated with depression: age (r = .212, P <
.05), reported monthly income of less than US $600 (F = 4.98, P = .001), lack of
exercise (F = 3.75, P = .027), history of stroke (t = -2.45, P = .016) and kidney
disease (t = -2.41, P = .018), unstable angina (F = 3.56, P = .031), and groin
puncture (F = 3.27, P = .042). A hierarchical regression model explained 43.7% of
the variance in depression. CONCLUSION: Social support, unstable angina, and
stroke may be important predictors of depression in patients with coronary heart
disease. These findings help clinical staff to understand physical and mental
health problems in cardiovascular patients. Thus, we suggest that early
depression prediction and sufficient social support can help patients to face
their disease and thus improve depression and health care quality.
PMID- 28489725
TI - Dog Ownership and Dog Walking: The Relationship With Exercise, Depression, and
Hopelessness in Patients With Ischemic Heart Disease.
AB - BACKGROUND: Dog ownership has been associated with increased physical activity in
the general adult population. OBJECTIVE: The objective of this study was to
examine dog ownership and dog walking and their relationship with home-based and
phase II cardiac rehabilitation exercise, depression, and hopelessness in
patients with ischemic heart disease. METHODS: A total of 122 patients with
ischemic heart disease were included in this prospective observational study.
Patients completed dog ownership/walking questions during their hospitalization.
The Cardiac Rehabilitation Exercise Participation Tool, Patient Health
Questionnaire-9, and State-Trait Hopelessness Scale were completed by mail at 3,
8, or 12 months later. Regression modeling was used to evaluate the significance
of dog ownership/walking on exercise, depression and hopelessness. RESULTS: The
sample was 34.4% female and had a mean age of 64.7 +/- 9.1 years. Forty-two
patients (34.4%) reported owning a dog. Patients who owned but did not walk their
dog reported significantly lower levels of home exercise compared with patients
who walked their dogs at least 1 day per week (36.8% for non-dog walkers vs 73.9%
for dog walkers, P = .019). The odds of participating in home exercise were
significantly higher for dog walkers compared with non-dog walkers (odds ratio,
8.1 [1.7, 38.5] vs 1.0). There were no differences in phase II cardiac
rehabilitation exercise, depression, or hopelessness between dog owners and non
dog owners or between dog walkers and non-dog walkers. CONCLUSIONS: These
findings show a beneficial effect on home-based exercise for those who dog-walk
at least 1 day per week. Healthcare professionals should encourage dog walking to
increase dog owners' physical activity levels.
PMID- 28489726
TI - A Systematic Review of Interventions to Improve Health Factors or Behaviors of
the Cardiovascular Health of Prisoners During Incarceration.
AB - BACKGROUND: Prisoners are disproportionately affected by cardiovascular disease
and its risk factors. However, primary prevention of cardiovascular disease in
correctional settings has been widely neglected, and there is little information
on interventions to improve the cardiovascular health of prisoners while
incarcerated. OBJECTIVE: The aim of this study was to systematically review
published literature to identify interventions to improve the health factors or
behaviors of the cardiovascular health of prisoners during incarceration.
METHODS: Selected databases were searched using terms related to prisoners and
cardiovascular disease. Studies were included if they had prisoners as
participants and measured outcomes of cardiovascular health. Narrative synthesis
was used to organize the evidence from the studies. RESULTS: Twelve articles
detailing 11 studies were identified. Most of the studies involved only men.
Interventions were classified into 4 types: structured physical activity,
nutrition, mixed with physical activity and educational sessions, and smoking
cessation. Most studies measured short-term outcomes relating to cardiovascular
health such as changes in blood pressure and weight. Only 4 studies were of high
quality. Structured physical activity interventions, nutrition interventions, and
smoking cessation interventions delivered in a group setting had significant
effects on at least 1 measured outcome. The effect of mixed interventions could
not be determined. CONCLUSIONS: Structured physical activity interventions,
nutrition interventions, and smoking cessation interventions delivered in a group
setting can improve health factors or behaviors of the cardiovascular health of
prisoners during incarceration. More high-quality research is needed to increase
the evidence base on the effectiveness of these interventions in the correctional
setting.
PMID- 28489727
TI - Pharmacology of Thiopurine Therapy in Inflammatory Bowel Disease and Complete
Blood Cell Count Outcomes: A 5-Year Database Study.
AB - BACKGROUND: Thiopurines are the prerequisite for immunomodulation in inflammatory
bowel disease (IBD) therapy. When administered in high (oncological) dose,
thiopurine metabolites act as purine antagonists, causing DNA-strand breakage and
myelotoxicity. In lower IBD dosages, the mode of action is primarily restricted
to anti-inflammatory effects. Then, myelosuppression and hepatotoxicity are the
most common adverse events of thiopurines. The aim of this study was to assess
the effect of thiopurine metabolites on hematologic and hepatic parameters and to
determine which patient characteristics are related to generation of thiopurine
metabolites. METHODS: The authors scrutinized the therapeutic drug monitoring
database of the VU University medical center and subsequently merged this
database with the Clinical Laboratory database of our hospital covering the same
time period (2010-2015). RESULTS: The authors included 940 laboratory findings of
424 unique patients in this study. Concentrations of 6-thioguanine nucleotides (6
TGN) correlated negatively with red blood cell count, white blood cell count, and
neutrophil count in both azathioprine (AZA) and mercaptopurine users. There was a
positive correlation with mean corpuscular volume. In patients using 6
thioguanine, 6-TGN concentrations correlated positively with white blood cell
count. Furthermore, there was an inverse correlation between patient's age and 6
TGN concentrations in patients using AZA or 6-thioguanine, and we observed an
inverse correlation between body mass index and 6-TGN concentrations in patients
using AZA or mercaptopurine. No relations were observed with liver test
abnormalities. CONCLUSIONS: Thiopurine derivative therapy influenced bone marrow
production and the size of red blood cells. Age and body mass index were
important pharmacokinetic factors in the generation of 6-TGN.
PMID- 28489728
TI - Novel Adjunct Drugs Reverse Endothelial Glycocalyx Damage After Hemorrhagic Shock
in Rats.
AB - INTRODUCTION: There is interest in the small-volume therapeutic use of adjunct
drugs for treating hemorrhagic shock (HS). However, critical information is only
partially available on mechanisms of action of promising compounds such as
adenosine-lidocaine-magnesium (ALM), beta-hydroxybutyrate plus melatonin (BHB/M),
and poloxamer 188 (P-188). Therefore, we tested the hypothesis that these
adjuncts would reverse HS-induced damage to microvascular endothelial glycocalyx
and hemodynamics. METHODS: After baseline, 40% of total blood volume was removed
from 44 anesthetized Sprague-Dawley male rats. One hour after hemorrhage, animals
were resuscitated using ALM, BHB/M, or P-188 followed by lactated Ringer's (LR,
15 mL/kg). Control animals were not treated (SHAM) or received LR alone. Sampled
blood was used to quantify shed syndecan-1 in plasma; multiple systemic
physiological parameters were recorded. In vivo glycocalyx thickness,
microvascular permeability, and microhemodynamics were evaluated in >200
cremaster venules using intravital videomicroscopy. RESULTS: Compared with
baseline, resuscitation using adjuncts was associated with glycocalyx restoration
of 97 +/- 9% (ALM), 75 +/- 8% (BHB/M), and 85 +/- 5% (P-188): significantly
higher than LR-only (56 +/- 4%). Significantly better permeability, similar to
SHAM values, was measured after ALM and P-188, and low plasma syndecan-1 levels
were measured after resuscitation with all adjuncts. Microhemodynamic changes
were relatively small while systemic parameters such as mean arterial pressure
and lactate improved but remained below or above the baseline, respectively, as
expected from this hypotensive resuscitation model. CONCLUSION: The drugs ALM,
BHB/M, and P-188 provide beneficial effects as adjuncts to hypotensive
resuscitation in this HS model by mechanisms involving changes at the
microvascular level including the glycocalyx.
PMID- 28489729
TI - Trends in ART Prescription and Viral Suppression Among HIV-Positive Young Adults
in Care in the United States, 2009-2013.
AB - BACKGROUND: Only 13% of HIV-positive young adults are estimated to be virally
suppressed and, even among those receiving medical care, HIV-positive young
adults are less likely than older adults to take antiretroviral therapy (ART), be
adherent, and be virally suppressed. We sought to examine trends in treatment and
health outcomes from 2009 to 2013 among HIV-positive young adults (aged 18-24
years) in care. SETTING: The Medical Monitoring Project is a complex sample
survey of HIV-infected adults receiving medical care in the United States.
METHODS: We used weighted interview and medical record data collected from June
2009 to May 2014 to estimate trends in the prevalence of ART prescription,
adherence, side effects, single-tablet ART regimens, regular care utilization,
and viral suppression among young adults. RESULTS: From 2009 to 2013, there were
significant increases in ART prescription (76%-87%) and the proportion of young
adults taking ART who reported taking single-tablet regimens (49%-62%). There was
no significant change in adherence, side effects, or regular care utilization.
Although viral suppression at last test did not change (65% at both time
periods), the proportion of young adults who were sustainably virally suppressed
significantly increased (29%-46%). Accounting for ART prescription and single
tablet regimen use attenuated the sustained viral suppression trend. CONCLUSIONS:
Although the level of viral suppression among young adults in care remains
suboptimal, the observed increases in ART prescription and sustained viral
suppression may be a cause for optimism regarding efforts to improve outcomes for
this vulnerable population.
PMID- 28489730
TI - Improved HIV-1 Viral Load Monitoring Capacity Using Pooled Testing With Marker
Assisted Deconvolution.
AB - OBJECTIVE: Improve pooled viral load (VL) testing to increase HIV treatment
monitoring capacity, particularly relevant for resource-limited settings. DESIGN:
We developed marker-assisted mini-pooling with algorithm (mMPA), a new VL pooling
deconvolution strategy that uses information from low-cost, routinely collected
clinical markers to determine an efficient order of sequential individual VL
testing and dictates when the sequential testing can be stopped. METHODS: We
simulated the use of pooled testing to ascertain virological failure status on
918 participants from 3 studies conducted at the Academic Model Providing Access
to Healthcare in Eldoret, Kenya, and estimated the number of assays needed when
using mMPA and other pooling methods. We also evaluated the impact of practical
factors, such as specific markers used, prevalence of virological failure, pool
size, VL measurement error, and assay detection cutoffs on mMPA, other pooling
methods, and single testing. RESULTS: Using CD4 count as a marker to assist
deconvolution, mMPA significantly reduces the number of VL assays by 52%
[confidence interval (CI): 48% to 57%], 40% (CI: 38% to 42%), and 19% (CI: 15% to
22%) compared with individual testing, simple mini-pooling, and mini-pooling with
algorithm, respectively. mMPA has higher sensitivity and negative/positive
predictive values than mini-pooling with algorithm, and comparable high
specificity. Further improvement is achieved with additional clinical markers,
such as age and time on therapy, with or without CD4 values. mMPA performance
depends on prevalence of virological failure and pool size but is insensitive to
VL measurement error and VL assay detection cutoffs. CONCLUSIONS: mMPA can
substantially increase the capacity of VL monitoring.
PMID- 28489734
TI - Treatment of distal splenic artery aneurysm by laparoscopic aneurysmectomy with
end-to-end anastomosis: A case report.
AB - RATIONALE: Splenic artery aneurysm (SAA) is the most common visceral artery
aneurysm, while most SAAs are treated by endovascular or open procedures. PATIENT
CONCERNS: Here we present a case of SAA treated by laparoscopic aneurysmectomy
with end-to-end anastomosis. DIAGNOSES: A 40-year-old woman was incidentally
found to have an asymptomatic distal SAA. CT scan revealed the SAA to be located
at the hilum of the spleen, with a maximal diameter of 2.7 cm. INTERVENTIONS: To
prevent sudden rupture, the patient received laparoscopic aneurysmectomy. During
the operation, end-to-end anastomosis was also performed since a tortuous
proximal splenic artery prevented delivery of the stent graft. OUTCOMES: The
patient was ambulated 12 hours after surgery and discharged 5 days later.
Postoperative recovery was smooth without hemorrhage, infarction, infection, or
splenic artery thrombosis. At 10-month follow-up,no hemorrhage, aneurysm
recurrence, spleen infarction, splenic artery stenosis, or thrombosis had
occurred. LESSONS: Patients with distal SAA can be treated by laparoscopic
aneurysmectomy with end-to-end anastomosis to preserve the spleen. The
laparoscopic procedure is safe and feasible in the selected patients.
PMID- 28489735
TI - Impact of a preoperative conversational hypnotic session on propofol consumption
using closed-loop anesthetic induction guided by the bispectral index: A
randomized controlled trial.
AB - OBJECTIVE: The automated administration of propofol in a closed loop could be
used to objectively evaluate the nonpharmacological anesthetic action of
hypnotherapy. The objective of this study was to evaluate the impact of a
conversational hypnosis session on the consumption of propofol for anesthetic
induction. DESIGN: A randomized, usual care-controlled, single-center, patient
blind trial. SETTING: Tertiary care center in France from November 2012 to
December 2013. PARTICIPANTS: Adult patients scheduled for a surgical procedure
under general anesthesia. INTERVENTIONS: Before surgery, patients were randomized
with a computer-generated random list for a preoperative conversational hypnosis
session or for usual care. The conversational hypnosis session was conducted and
individualized by the therapist with an academic degree in hypnosis in a quiet
environment. Anesthetic induction was automatically performed by propofol without
opioids and was assisted by the bispectral index in a closed loop. OUTCOME:
Primary endpoint was the propofol dose required for anesthesia induction, defined
as a Bispectral index less than 60 for at least 30 seconds. RESULTS: The study
included 48 patients in the hypnosis group and 49 patients in the control group.
No difference in propofol consumption to obtain anesthesia induction was observed
between the groups (total dose: 138.6 [67.5] and 130 [47.9] mg, P = .47; adjusted
dose: 2.15 [1.09] and 1.95 [0.66] mg/kg, P = .28, for the hypnosis and control
groups, respectively). Hetero-evaluation of arm movement during propofol
injection (no reaction: 98% and 74%; P = .004, in the hypnosis and control
groups, respectively) and face reaction at venous access placement (no reaction
59% and 30%; P = .017, in the hypnosis and control groups, respectively) were
lower in the hypnosis group. No adverse event was reported. CONCLUSIONS: No
difference in propofol consumption was observed in this study designed to
evaluate the effect of a hypnotic conversational session on anesthesia induction
using an automated tool for propofol administration.
PMID- 28489732
TI - Assessment of Nevirapine Prophylactic and Therapeutic Dosing Regimens for
Neonates.
AB - BACKGROUND: Nevirapine (NVP) is a key component of antiretroviral prophylaxis and
treatment for neonates. We evaluated current World Health Organization (WHO)
weight-band NVP prophylactic dosing recommendations and investigated optimal
therapeutic NVP dosing for neonates. METHODS: The PHPT-5 study in Thailand
assessed the efficacy of "Perinatal Antiretroviral Intensification" to prevent
mother-to-child transmission of HIV in women with <8 weeks of antiretroviral
treatment before delivery (NCT01511237). Infants received a 2-week course of
zidovudine/lamivudine/NVP (NVP syrup/once daily: 2 mg/kg for 7 days; then 4 mg/kg
for 7 days). Infant samples were assessed during the first 2 weeks of life. NVP
population pharmacokinetics (PK) parameters were estimated using nonlinear mixed
effects models. Simulations were performed to estimate the probability of
achieving target NVP trough concentrations for prophylaxis (>0.10 mg/L) and for
therapeutic efficacy (>3.0 mg/L) using different infant dosing strategies.
RESULTS: Sixty infants (55% male) were included. At birth, median (range) weight
was 2.9 (2.3-3.6) kg. NVP concentrations were best described by a 1-compartment
PK model. Infant weight and postnatal age influenced NVP PK parameters. Based on
simulations for a 3-kg infant, >=92% would have an NVP trough >0.1 mg/L after 48
hours through 2 weeks using the PHPT-5 and WHO-dosing regimens. For NVP-based
therapy, a 6-mg/kg twice daily dose produced a trough >3.0 mg/L in 87% of infants
at 48 hours and 80% at 2 weeks. CONCLUSION: WHO weight-band prophylactic
guidelines achieved target concentrations. Starting NVP 6 mg/kg twice daily from
birth is expected to achieve therapeutic concentrations during the first 2 weeks
of life.
PMID- 28489736
TI - Primary pulmonary meningioma: A case report.
AB - RATIONALE: Primary extracranial meningiomas are rare outside the head and neck
region. PATIENT CONCERNS: A 44-year-old female patient had chest pain for more
than 1 year. DIAGNOSES: Preoperative chest computed tomography (CT) scan revealed
a nodule in the right lower lobe, 1.8 cm in diameter. Tumor tissues were examined
by immunohistochemistry for vimentin and S-100. INTERVENTIONS:
Histopathologically, the tumor was characterized by whorled nests of spindle
shaped cells accompanied by psammoma bodies. Immunohistochemistry demonstrated
tumor cell positivity for vimentin and S-100. This case was diagnosed as a
primary pulmonary meningioma. The tumor was removed by a thoracoscopic pulmonary
wedge resection. OUTCOMES: Postoperative cranial and spinal CT scan did not show
any intracranial or spinal mass. No recurrence of the tumor was reported at the
time of writing up this case report. LESSONS: A primary pulmonary meningioma
should be considered in the differential diagnosis workup of pulmonary nodules.
PMID- 28489737
TI - Clinical effect of montelukast sodium combined with inhaled corticosteroids in
the treatment of OSAS children.
AB - This study was designed to investigate the clinical effect of montelukast sodium
combined with inhaled corticosteroids in the treatment of children with
obstructive sleep apnea syndrome (OSAS).One hundred ninety-five children were
enrolled and divided into 3 groups: groups A, B, and C; the group A (oral use of
montelukast sodium), group B (nasal spray of mometasone furoate), and group C
(oral use of montelukast sodium + nasal spray of mometasone furoate). Telephone
questionnaire surveys were carried out. Polysomnography monitoring was performed
and lateral x-ray radiographs of the cervical spine were taken before treatment
and at 12 weeks after treatment. The improvement of clinical symptoms after
treatment and its effective rate were analyzed. The difference in clinical
characteristics between groups C1 and C2 was analyzed.In the 3 groups, clinical
symptoms improved at 12 weeks after treatment compared with before (P < .05 or P
< .01). Apnea-hypopnea index value decreased (P < .05) and minimal SaO2 increased
(P < .05), while adenoidal/nasopharyngeal ratio was reduced (P < .05). Compared
with groups A and B, group C had a shortened response duration of snoring, apnea,
and restless sleep (P < .05). Differences in the response duration of buccal
respiration and hyperhidrosis were not statistically significant (P > .05). The
total effective rate was higher in group C than in A and B (P < .05), while the
differences in all indices between groups A and B were not statistically
significant (P > .05). The difference in the grade of the size of the tonsil
between groups C1 and C2 was statistically significant (P < .05).The total
effective rate of the combined treatment was higher than that of the single use
of any of the 2 drugs, which allowed the rapid relief of symptoms. Drug treatment
may have a poor curative effect in the treatment of OSAS patients with >= grade 3
tonsil hypertrophy.
PMID- 28489738
TI - Inhibitory member of the apoptosis-stimulating protein of p53 is overexpressed in
bladder cancer and correlated to its progression.
AB - Several lines of direct evidence show that inhibitory member of the apoptosis
stimulating protein of p53 (iASPP) has an important function in cancer
progression. However, its expression pattern and relationship with clinical
pathologic characteristics in bladder cancer (BC) have not been completely
elucidated. In this study, firstly, samples from 3 patients with invasive BC were
detected by liquid chromatography tandem mass spectrometry to confirm
overexpression of iASPP in BC, then samples from patients with noninvasive and
invasive BC were detected by real-time polymerase chain reaction, Western blot,
and tissue microarry immunohistochemistry. The relationship between iASPP
expression and various clinicopathological features was investigated. The results
showed m-RNA and protein of iASPP were overexpressed in BC and the rate of iASPP
positive cells was positively correlated with Union for International Cancer
Control-Tumor, Node, Metastases stage, histologic grade, lymph node metastasis
and poor overall survive. The data demonstrate that iASPP is overexpressed in BC
and promotes the malignancy of BC. iASPP maybe serve as a potential therapeutic
target for BC.
PMID- 28489739
TI - Diagnostic accuracy of DWI in patients with ovarian cancer: A meta-analysis.
AB - BACKGROUND: Diffusion weighted imaging (DWI) is recently developed for
identifying different malignant tumors. In this article the diagnostic accuracy
of DWI for ovarian cancer was evaluated by synthesis of published data. METHODS:
A comprehensive literature search was conducted in PubMed/MEDLINE and Embase
databases on the diagnostic performance of DWI for ovarian cancer published in
English. Methodological quality was evaluated following Quality Assessment for
Studies of Diagnostic Accuracy 2 (QUADAS 2) tool. We adopted the summary receiver
operating characteristic (SROC) curve to assess the DWI accuracy. RESULTS: Twelve
studies including 1142 lesions were analyzed in this meta-analysis to estimate
the pooled Sen (sensitivity), Spe (specificity), PLR (positive likelihood ratio),
NLR (negative likelihood ratio), and construct SROC (summary receiver operating
characteristics) curve. The pooled Sen and Spe were 0.86 (95% confidence interval
[CI], 0.83-0.89) and 0.81 (95%CI, 0.77-0.84), respectively. The pooled PLR and
pooled NLR were 5.07 (95%CI, 3.15-8.16) and 0.17 (95%CI, 0.10-0.30),
respectively. The pooled diagnostic odds ratio (DOR) was 35.23 (95%CI, 17.21
72.14). The area under the curve (AUC) was 0.9160. CONCLUSION: DWI had moderately
excellent diagnostic ability for ovarian cancer and promised to be a helpful
diagnostic tool for patients of ovarian cancer.
PMID- 28489740
TI - Percutaneous pinning after prolonged skeletal traction with the hip in a flexed
position for unstable slipped capital femoral epiphysis: A case series of 11
patients.
AB - BACKGROUND: Unstable slipped capital femoral epiphysis (SCFE) has a relatively
high risk of avascular necrosis of the femoral head. Standard treatment for
unstable SCFE is still controversial. We reviewed unstable SCFE case series
treated with the standardized protocol, which consisted of percutaneous pinning
after prolonged skeletal traction. METHODS: Our treatment regimen for unstable
SCFE patients included 1 week or more of skeletal traction with the hip in a
flexed position of 45 degrees, and subsequent percutaneous pinning after
unintentional reduction. Eleven patients were treated in our institution and an
affiliated hospital between 2003 and 2013. Sex, age at surgery, body mass index,
the presence of hormonal abnormality, duration between onset and surgery, head
shaft angle, posterior tilting angle, and modified Harris hip score were
investigated from the medical records and radiographs. RESULTS: There were 8 male
and 3 female with an average age of 11.7 years and an average body mass index of
24.5 kg/mm. No patients had hormonal abnormalities. The duration between onset
and surgery ranged from 8 to 16 days. The average preoperative and postoperative
head shaft angles were 126 and 141 degrees, respectively. Postoperative posterior
tilting angle was averaged of 30.7 degrees, which decreased to 21.5 degrees
during follow-up period. One patient showed mild avascular necrosis only
confirmed by magnetic resonance imaging, but he was uneventfully treated without
additional procedures. As a result, all patients had a perfect modified Harris
hip score of 91 points. CONCLUSIONS: Prolonged traction with the hip in a flexed
position may not only provide gradual reduction of posteriorly displaced
epiphysis but also decrease intra-articular pressure before surgery. Although
percutaneous pinning after unintentional reduction leaves mild displacement of
the femoral epiphysis, remodeling could be expected during remaining growth
period.
PMID- 28489741
TI - Salmonella enterica serovar Panama meningitis in exclusive breastfeeding infants:
Report of 4 cases, clinical features and therapeutic challenges.
AB - RATIONALE: The pathway of Nontyphoid Salmonella meningitis, especially in
exclusive breastfeeding infants, has not been well characterized. PATIENT
CONCERNS: We analyzed data related to nontyphoid Salmonella meningitis in 4
infants. DIAGNOSES: No diarrhea was observed and the coproculture was negative
for all patients. INTERVENTIONS: Early diagnosis and treatment with combination
of third-generation cephalosporins plus quinolones for a minimum of 3 weeks is
necessary to avoid severe sequelae and death. OUTCOMES: The first 3 patients had
a good evolution, whereas the last patient had multiple brain abscesses and
hydrocephalus requiring treatment with a ventriculoperitoneal shunt. LESSONS: The
highlights of our study are that all infants were exclusively breastfed, no
diarrhea observed and the negative coproculture for all the 4 patients, which is
relatively rare for Salmonella infection.
PMID- 28489743
TI - Narrow-band imaging endoscopy is advantageous over conventional white light
endoscopy for the diagnosis and treatment of children with Peutz-Jeghers
syndrome.
AB - Using narrow-band imaging (NBI), the micro morphology of polyp surfaces was
visualized at high resolution when the contrast between the lesions and the
surrounding tissue areas was intensified. The objective of the study was to
compare NBI and conventional white light endoscopy (C-WLI) for diagnostic
efficacy and treatment of children with Peutz-Jeghers syndrome (PJS), a rare
autosomal dominant-genetic disease.We retrospectively analyzed the clinical data
of 18 patients diagnosed with PJS and 72 diagnosed with juvenile polyps during
the same time period. Endoscopy was used to observe the morphology of polyps,
which were classified according to the Kudo pit pattern. Eighty-two and 76 polyps
were resected using endoscopy from PJS and juvenile polyp patients, respectively,
and pathologically examined for comparison with NBI or C-WLI endoscopic
observations.With NBI, 57 (69.5%) type I, 10 (12.2%) type II, and 13 (15.9%) type
III polyps were identified in 82 (100%) polyps excised from 18 PJS patients,
whereas 69 (88.5%) type I, 5 (6.4%) type II and 4 (5.1%) type III were identified
in 78 (100%) of polyps removed from 72 juvenile polyp patients. The combined
ratios of types II and III were higher in PJS (28.1%) than in juvenile polyp
patients (11.5%). Pathological diagnosis identified 69 of 82 PJS polyps as
hamartoma and 13 as adenoma, whereas NBI detected 10 adenomas and C-WLI only 4.
The sensitivity, specificity, and accuracy of NBI in the diagnosis of adenoma
were 76.9%, 97.1%, and 93.9%, respectively, whereas those of C-WLI were 30.8%,
94.2%, and 84.1%.NBI endoscopy had higher sensitivity and specificity than C-WLI
for the diagnosis of adenomatous polyps and is recommended for the diagnosis,
characterization, and resection of polyps in children with PJS.
PMID- 28489742
TI - Circulating TNF receptors predict cardiovascular disease in patients with chronic
kidney disease.
AB - Cardiovascular disease (CVD) is the main public health problem in patients with
chronic kidney disease (CKD); however, there is no established biomarker for
predicting CVD morbidity and mortality in CKD. The aim of this study was to
evaluate the role of circulating tumor necrosis factor receptors (cTNFRs) in
predicting CVD risk in CKD patients.We prospectively recruited 984 patients with
CKD from 11 centers between 2006 and 2012. The levels of cTNFR1 and cTNFR2 were
determined by performing an enzyme-linked immunosorbent assay. During the mean
follow-up period of 4 years, 36 patients experienced a CVD event. The median
serum concentrations of cTNFR1 and cTNFR2 were 2703.4 (225.6-13,057.7) and 5661.0
(634.9-30,599.6) pg/mL, respectively, and the cTNFR1 level was closely correlated
with the cTNFR2 level (r = 0.86, P < .0001). The urinary protein-to-creatinine
ratio (UPCR) and estimated glomerular filtration rate (eGFR) were significantly
correlated with the cTNFR2 level (r = 0.21 for UPCR, r = -0.67 for eGFR; P < .001
for all). Similar correlations were observed for serum cTNFR1 (r = 0.21 for UPCR,
r = -0.75 for eGFR; P < .001 for all). In the Cox proportional hazard analyses,
cTNFR1 (hazard ratio [HR] 2.506, 95% confidence interval [CI] 1.186-5.295, P =
.016) and cTNFR2 (HR 4.156, 95% CI 1.913-9.030, P < .001) predicted CVD risk even
after adjustment for clinical covariates, such as UPCR, eGFR, and high
sensitivity C-reactive protein. cTNFR1 and 2 are associated with CVD and other
risk factors in CKD, independently of eGFR and UPCR. Furthermore, cTNFRs could be
relevant predictors of CVD in CKD patients.
PMID- 28489745
TI - Adverse local tissue reaction after 2 revision hip replacements for ceramic liner
fracture: A case report.
AB - INTRODUCTION: In younger patients, ceramic-on-ceramic (CoC) bearing surfaces are
usually recommended for total hip replacement (THR) because of their low wear
rate and longer expected functional life. Although technical advancements have
reduced the risk of ceramic bearings fracture, this complication remains a major
concern. CASE DESCRIPTION: We present the case of a 56-year-old patient
undergoing 3 revision hip arthroplasties of the right hip due to ceramic liner
fractures. Initial THR (2008) was performed with a CoC bearing, followed by liner
fracture due to trauma a year later. The acetabular component and liner were
replaced, with a minor incongruence between the old head and new insert. The 2nd
ceramic insert fractured 3.5 years later, following minor trauma. Upon revision,
the bearing surface was changed to metal-on-polyethylene (MoP). The performed
retrieval analysis demonstrated stripe and rim wear, and evidence of adhesive
wear. The patient was referred to us a month later, with a fistula on the lateral
side of the hip, discharging black, petroleum-like liquid. Radiology showed well
fixed implants, no dislocation and no apparent polyethylene wear. Microbiological
assessment of the discharge showed no infection. Intraoperatively massive
metallosis was noticed, with stable acetabular and femoral components. The metal
femoral head was heavily abraded, with almost 1% volumetric wear. Hematoxylin and
eosin stained frozen tissue samples showed muscular and adipose tissue necrosis,
while polarized light microscopy highlighted metal, polyethylene, and ceramic
particles. CONCLUSION: The present case is yet another report showing the adverse
outcomes of using MoP bearings for revision after ceramic liner fracture in THR.
PMID- 28489744
TI - Diagnostic accuracy of SPECT, PET, and MRS for primary central nervous system
lymphoma in HIV patients: A systematic review and meta-analysis.
AB - BACKGROUND: We performed a systematic review and meta-analysis to assess the
roles of SPECT, PET, and MRS in distinguishing primary central nervous system
lymphoma (PCNSL) from other focal brain lesions (FBLs) in human immunodeficiency
virus (HIV)-infected patients. METHODS: PubMed, Scopus, and Medline were
systematically searched for eligible studies from 1980 to 2016. Two authors
extracted characteristics of patients and their lesions using predefined
criteria. RESULTS: Eighteen studies on SPECT containing 667 patients, 6 studies
on PET containing 108 patients, and 3 studies on MRS containing 96 patients were
included. SPECT had a pooled sensitivity of 0.92 (95% CI: 0.85-0.96) and
specificity of 0.84 (95% CI: 0.74-0.90) in differentiating PCNSL from other FBLs.
For the 6 studies that used only pathology and/or serology as the gold standard,
the pooled sensitivity was 0.85 (95% CI: 0.72-0.97) and the pooled specificity
was 0.73 (95% CI: 0.54-0.92). CONCLUSION: SPECT has good diagnostic accuracy for
discriminating PCNSL from other FBL-causing disorders in HIV patients. However,
the actual sensitivity and specificity of SPECT may be lower than expected if
only pathology and/or serology was used as the gold standard. PET may be superior
but has less supporting clinical data and is more expensive.
PMID- 28489746
TI - Pediatric esophagopleural fistula: Two case reports and a literature review.
AB - Esophagopleural fistula (EPF) is rarely reported in children with a high
misdiagnosis rate. This study aimed to reveal the clinical manifestations and
managements of EPF in children.Two pediatric cases of EPF in our hospital were
reported. A bibliographic search was performed on the PubMed, WANFANG, and CNKI
databases for EPF-related reports published between January 1980 and May 2016.
The pathogeny, clinical manifestations, diagnosis, treatments, and prognosis of
EPF patients were collected and discussed.Based on conservative treatments, 1
pediatric EPF case induced by cervical trauma was cured by longitudinal septum
incision-mediated drainage. The other pediatric EPF induced by endoscopic balloon
dilation was cured by dual stent implantation. A total of 38 studies of 197 EPF
patients (191 adults and 6 children) were reviewed. Latrogenic factor, esophageal
foreign body, and infection are considered the main causes of EPF in children.
Unilateral pleural effusion accompanied by food residue was the main
manifestations of EPF. Chest computed tomography (CT) and contrast esophagography
were usually used in the diagnosis of EPF with high accuracy. Surgical treatment
in adults with EPF exhibited a significantly higher cure rate and lower mortality
rate than conservative treatment (P < .01).Pleural effusion with food residue is
a specific finding in EPF. Chest CT exhibited high sensitivity for the diagnosis
of EPF. Conservative treatment may be preferable for pediatric patients with EPF.
PMID- 28489747
TI - Postoperative changes in the retinal thickness and volume after vitrectomy for
epiretinal membrane and internal limiting membrane peeling.
AB - The aim of the study was to investigate the thickness and volume profiles of each
retinal layer in postoperative patients with epiretinal membranes.Twenty-four
patients who underwent pars plana vitrectomy with internal limiting membrane
(ILM) peeling for epiretinal membrane were included. The best corrected visual
acuity, thickness, and volume were recorded from the medical records through a
retrospective review. Spectral domain optical coherence tomography was used to
measure the average thickness and volume of each retinal layer before surgery and
6 months postoperatively.All 24 patients were monitored for 60 months after
surgery. In all Early Treatment Diabetic Retinopathy Study (ETDRS) subfields, the
thickness and volume of the retinal nerve fiber layer and the inner retinal layer
decreased significantly. In contrast, the thickness and volume of the ganglion
cell layer, inner nuclear layer, inner plexiform layer, and outer plexiform layer
only decreased in some ETDRS subfields. Finally, there was no significant change
in the thickness or volume of the outer nuclear layer (ONL), retinal pigment
epithelium (RPE), and photoreceptor layers in all ETDRS subfields.The thickness
and volume of the inner retina layer decreased significantly after pars plana
vitrectomy using ILM peeling. However, there was no significant change in the
thickness and volume of the outer retinal layers (ONL, RPE, and photoreceptor)
after surgery.
PMID- 28489748
TI - P16 protein expression as a useful predictive biomarker for neoadjuvant
chemotherapy response in patients with high-grade osteosarcoma: A systematic meta
analysis under guideline of PRISMA.
AB - BACKGROUND: Neoadjuvant chemotherapy for patients with high-grade osteosarcoma
has highly improved the clinical survival. However, the prognostic and predictive
role of P16 expression after neoadjuvant chemotherapy remains unclear. We first
determined whether P16 expression can become a potential prognostic and
predictive biomarker in high-grade osteosarcoma. METHODS: This meta-analysis was
conducted based on the Preferred Reporting Items for Systematic reviews and Meta
Analyses (PRISMA) guideline. Eligible studies were pooled and the overall odds
ratios (ORs) and hazard ratios (HRs) with the corresponding 95% confidence
intervals (95% CIs) were calculated in this analysis. RESULTS: Four studies
involving a total of 527 patients with high-grade osteosarcoma receiving
neoadjuvant chemotherapy were identified. We did not find that P16 expression was
correlated with sex status, histologic subtype, and tumor site (P > .1). P16
expression was found to be significantly associated with a "good" response to
neoadjuvant chemotherapy (OR = 4.69, P < .001). A significant relationship was
observed between p16 expression and pathologic complete response after
neoadjuvant chemotherapy using multivariate analysis (OR = 9.63, P = .001). The
expression of the P16 was not associated with clinical outcomes in overall
survival (OS) and disease-free survival (DFS) by multivariate analysis (OS: P =
.448; DFS: P = .263). CONCLUSIONS: The use of P16 expression could become a
promising predictive biomarker of the response to neoadjuvant chemotherapy in the
white population with high-grade osteosarcoma. However, it was not correlated
with the prognosis of patients in OS and DFS. More clinical researches are very
essential in Asians in the future.
PMID- 28489749
TI - Association between PAX7 and NTN1 gene polymorphisms and nonsyndromic orofacial
clefts in a northern Chinese population.
AB - BACKGROUND: Nonsyndromic orofacial clefts (NSOC) are the most common orofacial
congenital defect with a complex etiology. Genome-wide association studies have
identified paired box protein 7 (PAX7) and netrin-1 (NTN1) as candidate
susceptibility genes for NSOC in both European and Asian populations. Here,
possible associations between single-nucleotide polymorphisms (SNPs) in or near
PAX7 and NTN1 were investigated in relation to risk of NSOC in a northern Chinese
population. METHODS: A total of 602 individuals with NSOC and 510 controls were
recruited from northern China. Polymerase chain reaction-ligation detection
reactions were used to analyze 4 SNPs (rs742071, rs6659735, rs766325, and
rs4920520) of PAX7 and 2 SNPs (rs9904526 and rs9788972) of NTN1. Investigations
of polymorphisms and risk of NSOC were conducted by using the PLINK software.
RESULTS: NTN1 rs9788972 AG was found to be associated with an increased risk of
NSOC compared to the GG homozygous genotype (OR = 1.43, 95% CI = 1.11-1.86, P =
.006). When the multifactor dimensionality reduction method was applied, NTN1
rs9788972 still exhibited an increased risk for NSOC (P = .008). In contrast,
SNPs in PAX7 were not associated with any increased risk of NSOC. CONCLUSION:
NTN1 rs9788972 is identified as a risk locus for NSOC susceptibility in a
northern Chinese population.
PMID- 28489750
TI - Performance of the LACE index to identify elderly patients at high risk for
hospital readmission in Singapore.
AB - Unplanned readmissions may be avoided by accurate risk prediction and appropriate
resources could be allocated to high risk patients. The Length of stay, Acuity of
admission, Charlson comorbidity index, Emergency department visits in past six
months (LACE) index was developed to predict hospital readmissions in Canada. In
this study, we assessed the performance of the LACE index in a Singaporean cohort
by identifying elderly patients at high risk of 30-day readmissions. We further
investigated the use of additional risk factors in improving readmission
prediction performance.Data were extracted from the hospital's electronic health
records (EHR) for all elderly patients >= 65 years, with alive-discharge episodes
from Singapore General Hospital in 2014. In addition to LACE, we also collected
patients' data during the index admission, including demographics, medical
history, laboratory results, and previous medical utilization.Among the 17,006
patients analyzed, 2051 or 12.1% of them were observed 30-day readmissions. The
final predictive model was better than the LACE index in terms of discriminative
ability; c-statistic of LACE index and final logistic regression model was 0.595
and 0.628, respectively.The LACE index had poor discriminative ability in
identifying elderly patients at high risk of 30-day readmission, even if it was
augmented with additional risk factors. Further studies should be conducted to
discover additional factors that may enable more accurate and timely
identification of patients at elevated risk of readmissions, so that necessary
preventive actions can be taken.
PMID- 28489751
TI - Polyp missing rate and its associated risk factors of referring hospitals for
endoscopic resection of advanced colorectal neoplasia.
AB - Missed polyps are frequently observed in surveillance colonoscopy or referral
resection. We evaluated the polyp missing rate and its associated risk factors in
patients who were referred to a tertiary hospital for endoscopic resection of
advanced colorectal neoplasia.A total of 388 patients with advanced neoplasia who
underwent colonoscopy in their referring hospitals and only endoscopic resection
without total colonoscopy in Pusan National University Yangsan Hospital from 2009
to 2014 and who underwent surveillance colonoscopy within 6 to 12 months were
retrospectively analyzed.The per-patient missing rate for polyps, adenomas, and
advanced neoplasia in referring hospital were 58.2% (226 cases), 47.2% (183
cases), and 5.7% (22 cases), respectively. The advanced neoplasia in surveillance
colonoscopy comprised the following: >=1 cm lesions (11 cases, 50%), high-grade
dysplasia (4 cases, 18.2%), villous adenoma (4 cases, 18.2%), and invasive cancer
(3 cases, 13.6%). Risk factors for missed adenomas in multivariate analysis were
>=60 years (P = .004), male (P <.001), and no usage of the cap-assisted
colonoscopy (P = .015). Missed polyps/adenomas were most frequent in the
ascending colon (P <.001).The missing rate for polyps/adenomas of referring
hospitals was higher than expected. Especially, patients with old age or male, or
no usage of cap-assisted colonoscopy on initial colonoscopy were at increased
risk of missed adenoma. Careful complete colonoscopy during referral resection or
early surveillance colonoscopy is mandatory in the patients with advanced
colorectal neoplasia and unknown-quality index colonoscopy.
PMID- 28489752
TI - Enteric hyperoxaluria in chronic pancreatitis.
AB - Chronic pancreatitis may lead to steatorrhea, enteric hyperoxaluria, and kidney
damage. However, the prevalence and determinants of hyperoxaluria in chronic
pancreatitis patients as well as its association with renal function decline have
not been investigated.We performed an observational study. Urine oxalate to
creatinine ratio was assessed on 2 independent random urine samples in
consecutive adult patients with chronic pancreatitis followed at the outpatient
clinic from March 1 to October 31, 2012. Baseline characteristics and annual
estimated glomerular filtration rate (eGFR) change during follow-up were compared
between patients with hyper- and normo-oxaluria.A total of 48 patients with
chronic pancreatitis were included. The etiology of the disease was toxic (52%),
idiopathic (27%), obstructive (11%), autoimmune (6%), or genetic (4%).
Hyperoxaluria (defined as urine oxalate to creatinine ratio >32 mg/g) was found
in 23% of patients. Multivariate regression analysis identified clinical
steatorrhea, high fecal acid steatocrit, and pancreatic atrophy as independent
predictors of hyperoxaluria. Taken together, a combination of clinical
steatorrhea, steatocrit level >31%, and pancreatic atrophy was associated with a
positive predictive value of 100% for hyperoxaluria. On the contrary, none of the
patients with a fecal elastase-1 level >100 MUg/g had hyperoxaluria. Longitudinal
evolution of eGFR was available in 71% of the patients, with a mean follow-up of
904 days. After adjustment for established determinants of renal function decline
(gender, diabetes, bicarbonate level, baseline eGFR, and proteinuria), a urine
oxalate to creatinine ratio >32 mg/g was associated with a higher risk of eGFR
decline.Hyperoxaluria is highly prevalent in patients with chronic pancreatitis
and associated with faster decline in renal function. A high urine oxalate to
creatinine ratio in patients with chronic pancreatitis is best predicted by
clinical steatorrhea, a high acid steatocrit, and pancreatic atrophy. Further
studies will need to investigate the mechanisms of renal damage in chronic
pancreatitis and the potential benefits of therapies reducing oxaluria.
PMID- 28489753
TI - Effect of FOLFIRINOX as second-line chemotherapy for metastatic pancreatic cancer
after gemcitabine-based chemotherapy failure.
AB - BACKGROUND: This study aimed to determine the maximum tolerated dose (MTD), dose
limiting toxicity, and efficacy of second-line chemotherapy with FOLFIRINOX after
gemcitabine (GEM)-based chemotherapy failure in metastatic pancreatic cancer
(MPC). METHODS: We studied 18 histopathologically proven MPC patients. The
schedule was 85 mg/m oxaliplatin, irinotecan, and 400 mg/m leucovorin, followed
by 400 mg/m 5-fluorouracil (5-FU) as a bolus on day 1 and 2400 mg/m 5-FU as a 46
hour continuous infusion biweekly. The dose of irinotecan was defined as follows:
level 0: 100 mg/m, level 1: 125 mg/m, level 2: 150 mg/m, and level 3: 180 mg/m.
The doses of other drugs were fixed. The primary endpoint of phase II study was
the response rate (RR). RESULTS: We initially evaluated 6 patients in a phase I
study. One patient developed neutropenia and 1 patient developed hyperglycemia
and severe infection. Accordingly, level 1 was chosen as the MTD. According to a
phase II study, the RR was 22.2% and the disease control rate was 61.1%. The
progression-free survival and overall survival were 2.8 (range, 0.7-19.1) and 9.8
(2.4-19.8) months, respectively. The most common severe adverse event was
neutropenia (66.7%). Febrile neutropenia occurred in 1 (5.6%) case. CONCLUSION:
The recommended dose was 85 mg/m oxaliplatin, 100 mg/m irinotecan, and 400 mg/m
leucovorin, followed by 400 mg/m 5-FU as a bolus on day 1 and 2400 mg/m 5-FU as a
46-hour continuous infusion. These results indicate that second-line FOLFIRINOX
is a marginally effective treatment for GEM-based chemotherapy failure cases.
PMID- 28489754
TI - Relationship between SRD5A2 rs9282858 polymorphism and the susceptibility of
prostate cancer: A meta-analysis based on 20 publications.
AB - The pathogenetic mechanism of prostate cancer (PCa) has not been understood
completely, and gene polymorphisms have been demonstrated to play a critical role
in the course. It has been reported that rs9282858 polymorphism of steroid 5
alpha-reductase type 2 (SRD5A2) may affect the susceptibility of PCa, but some
researches showed different results. We therefore carried out a meta-analysis to
clarify this relationship.Relevant studies were identified through PubMed and
Chinese National Knowledge Infrastructure databases concerning the association
between SRD5A2 rs9282858 polymorphism and PCa. Odds ratios (ORs) with their 95%
confidence intervals (95% CIs) were calculated to assess the strength of the
association. Additionally, stratified analyses were performed based on ethnicity
and source of control. Besides, heterogeneity test, sensitivity analysis, and
publication bias evaluation were conducted in current meta-analysis as
well.Ultimately, 20 publications incorporating 30 case-control studies were
included in this meta-analysis, involving a total of 7300 cases and 7952
controls. The overall results demonstrated that SRD5A2 rs9282858 polymorphism was
remarkably associated with increased susceptibility of PCa (TT vs. AA: OR = 4.08,
95% CI = 1.94-8.58; TT + AT vs. AA: OR = 1.28, 95% CI = 1.11-1.47; TT vs. AA +
AT: OR = 4.44, 95% CI = 2.12-9.27; allele T vs. allele A: OR = 1.34, 95% CI =
1.17-1.54). After subgroup analyses by ethnicity and source of control, we also
observed a similar trend in Latinos, other-ethnicity, population-based, and
hospital-based groups under corresponding genetic models.Our findings indicate
that SRD5A2 rs9282858 polymorphism may be a susceptible factor to PCa.
PMID- 28489755
TI - Kennedy disease with difficulty in differential diagnosis: A case report.
AB - RATIONALE: Kennedy disease (KD) is also known as spinal bulbar muscular
dystrophy. As KD has similar symptoms with most neuromuscular diseases, so it is
difficult to make a rapid diagnosis clinically. PATIENT CONCERNS: We report a
case of a 43-year-old male with progressive limb proximal weakness without family
history. Physical examination showed gynecomastia, erectile dysfunction,
bilateral tendon reflex and quadriceps weakness, and tongue muscle atrophy.
DIAGNOSES: Laboratory examination found increased creatine kinase, impaired
glucose tolerance, and abnormal lactic acid values. There was no mutation or copy
number variant in SMN1 gene and related mitochondrion genes tested, even with the
use of multiplex ligation probe- dependent amplification technique. Diagnosis was
confirmed with genetic analysis which displayed trinucleotide CAG (glutamine)-
repeat expansion in the androgen-receptor gene. INTERVENTIONS AND OUTCOMES: The
patient achieved good prognosis with symptomatic treatment after diagnosis.
LESSONS: To diagnose KD, clinicians should pay more attention to differentiate KD
and myasthenia gravis, mitochondrial myopathy, and amyotrophic lateral sclerosis.
Gene analysis was the key in detecting this rare confusing disease in the
patient.
PMID- 28489757
TI - Ultrasound-guided catheterization of the left subclavian vein without recognition
of persistent left superior vena cava: A case report.
AB - RATIONALE: A persistent left superior vena cava (PLSVC) is rare, but the most
common thoracic venous anomaly. We report a case of PLSVC unrecognized during
left subclavian vein catheterization using real-time ultrasound-guided
supraclavicular approach. PATIENT CONCERNS: A 79-year-old man with history of
hypertension presented with traumatic subdural hemorrhage, subarachnoid
hemorrhage, and epidural hemorrhage. Before the operation, a central venous
catheter (CVC) was placed into the left subclavian vein. DIAGNOSES: A dilated
coronary sinus on echocardiogram and subsequent agitated saline test confirmed
the diagnosis of PLSVC. INTERVENTIONS: A CVC was placed into the left subclavian
vein under real-time ultrasound guide, with supraclavicular approach. A
postoperative chest X-ray revealed a left-sided paramediastinal course of the
CVC; the CVC was removed under the impression of malposition. OUTCOMES: The CVC
functioned properly. LESSONS: Ultrasound is used for safe and correct placement
of CVC; however, the presence of PLSVC could not be detected by ultrasonography
in this case. When the chest radiograph shows the central venous catheter passing
along the border of the left heart and a dilated coronary sinus detected on
echocardiogram, we should have suspicion of a PLSVC.
PMID- 28489756
TI - The genetic association between polymorphisms in lymphotoxin-alpha gene and
ankylosing spondylitis susceptibility in Chinese group: A case-control study.
AB - The study was designed to reveal the genetic relationship of lymphotoxin-alpha
(LTA) polymorphisms with risk of ankylosing spondylitis (AS) in Chinese Han
population.LTA polymorphisms were genotyped by polymerase chain reaction-direct
sequencing (PCR-DS) in 138 AS patients and 141 healthy controls. The genotype
distribution in control group was checked the status of Hardy-Weinberg
equilibrium (HWE). Odds ratio (OR) with 95% confidence interval (95%CI)
calculated by chi test was used to show effects of LTA polymorphisms on AS risk.
Logistic regressive analysis was used to calculate the adjusted OR values.
Additionally, the linkage disequilibrium of LTA polymorphisms was examined by
Haploview.G allele of rs909253 was significantly higher frequency in AS patients
(P = .02), which was associated with the increased risk of AS (OR = 1.53, 95%CI =
1.07-2.18). The carriages of GG genotype in rs909253 showed a high risk of AS
occurrence, compared with AA genotype carriers (OR = 2.46, 95%CI = 1.13-5.35).
Multivariate analysis demonstrated that the G allele (OR = 1.52, 95%CI = 1.05
2.15) and GG genotype (OR = 2.36, 95%CI = 1.06-5.24) of rs909253 were still
positively associated with AS susceptibility. However, there was no significant
association between AS risk and rs2239704 or rs2229094.LTA rs909253 polymorphism
contributes to the occurrence of AS.
PMID- 28489759
TI - Shen-Cao granules formulated based on traditional Chinese medicine alleviates
bone marrow suppression caused by platinum-based anticancer reagents.
AB - BACKGROUND: The aim of this study was to evaluate effects of Shen-Cao granules
for the prevention of thrombocytopenia caused by anticancer chemotherapy.
METHODS: In this prospective study, a total of 200 patients with various
malignant tumors were enrolled and evenly divided into a Shen-Cao granule
treatment (n = 100) and a control group (n = 100). After 2 cycles chemotherapy
with any combination of platinum-based drugs (cisplatin, carboplatin, and
nedaplatin), the blood platelet (PLT) counts, levels of the PLT production
regulator thrombopoietin (TPO), PLT aggregation rates, and the PLT activation
marker CD62P expressions were monitored for 2 weeks. RESULTS: During 2 weeks of
post-chemotherapy, the mean values of the minimum PLT count were 49.65 +/- 7.35 *
10/L in the treatment group and 31.56 +/- 9.32 * 10/L in the control group. The
PLT count in the treatment group reached the lowest value 1.8 days later and
recovered to a concentration >=100 * 10/L 3 days earlier than in the control
group. The concentrations of the TPO were 71.43 +/- 1.74 and 87.24 +/- 0.92 ng/mL
in the treatment group and 65.75 +/- 1.39 and 67.75 +/- 0.67 ng/mL in the control
group at 7 and 14 days post-chemotherapy, respectively. The maximum PLT
aggregation rate declined after chemotherapy in the treatment group from 58.14 +/
11.46% to 52.89 +/- 10.52%, while it increased in the control group from 56.94
+/- 10.55% to 61.75 +/- 12.26%. Coordinately, the expression of CD62P in the
treatment group decreased from 6.17 +/- 0.59% to 4.89 +/- 0.72%, while it
increased from 6.09 +/- 0.75% to 7.75 +/- 0.67% in the control group. CONCLUSION:
Our study demonstrated that Shen-Cao granule treatment alleviated
thrombocytopenia after chemotherapy, and reduced tumor-induced PLT activation and
aggregation.
PMID- 28489758
TI - Analysis of radioiodine therapy and prognostic factors of differentiated thyroid
cancer patients with pulmonary metastasis: An 8-year retrospective study.
AB - To assess the efficacy of radioiodine therapy (RIT) and investigate the
prognostic factors for patients with pulmonary metastasis secondary to
differentiated thyroid carcinoma (DTC) through a retrospective study. A total of
80 patients with radioactive iodine-131 (I)-avid pulmonary metastasis from DTC
treated with I from 2007 to 2014 at our institution entered the study. Treatment
response was mainly measured by two parameters: serum thyroglobulin (Tg) levels
and post-therapeutic I whole-body scan (WBS). Treatment variables were assessed
for statistical significance using the univariate and multivariate analyses. A
receiver-operating characteristic (ROC) curve was also plotted to verify the
accuracy of predictors. Of these 80 patients, the overall effective rate was
72.5% (58/80), the rates for complete response (CR), partial response (PR), and
no response (NR) were 20.0%, 52.5%, and 27.5%, respectively. Univariate analysis
showed that gender, pulmonary nodule size, absence or presence of extrapulmonary
distant metastases, age, and Tg level at diagnosis were significantly associated
with I therapy efficacy. Binary logistic regression analysis revealed that older
patients (odds ratio [OR]:1.481, 95% confidence interval [CI]: 1.457-2.091, P =
.020), subjects with higher Tg levels at diagnosis (OR: 1.046, 95% CI: 1.016
1.119, P = .014), and those with extrapulmonary distant metastases (OR: 1.185,
95%CI: 1.025-1.463, P = .020) had a higher probability of poor prognosis. The
optimal cutoffs for age and Tg level to predict I therapy efficacy for DTC with
lung metastases were 46 years old and 55.50 ng/mL, respectively, based on ROC
analysis. This study indicated that most DTC patients with pulmonary metastases
can obtain partial or complete remission after RIT, while older patients with
higher Tg levels at diagnosis and extrapulmonary distant metastases more likely
show poor prognosis.
PMID- 28489760
TI - Chronic obstructive pulmonary disease is independently associated with
hypertension in men: A survey design analysis using nationwide survey data.
AB - Although studies have shown that chronic obstructive pulmonary disease (COPD) and
hypertension are linked as comorbidities, it remains unclear whether COPD is
independently associated with the risk of hypertension or is caused by common
risk factors such as age and smoking. The objective of this study was to
investigate the relationship between COPD and hypertension by using nationally
representative data.This cross-sectional study analyzed data from the Korea
National Health and Nutrition Examination Survey V conducted during 2010 to 2012.
Hypertension was defined as a mean systolic blood pressure >= 140 mm Hg and/or a
diastolic blood pressure >= 90 mm Hg, or current consumption of antihypertensive
medications. A diagnosis of COPD was defined as a smoking history of at least 10
pack-years with airflow limitation on spirometry. Multivariate logistic
regression was performed to investigate the independent association between COPD
and hypertension after adjusting for covariates. Survey design analyses were
conducted for all analyses.Among 4043 men (aged >= 40 years) who underwent
spirometry, 2190 (54.2%) had hypertension. Even after adjusting for age, body
mass index, smoking status, diabetes, metabolic syndrome, and stroke, COPD was
independently associated with hypertension (adjusted odds ratio, 1.71; 95%
confidence interval, 1.37-2.13; P < .001). Adjusted pulse pressure significantly
increased as the ratio of forced expiratory volume in 1 s (FEV1) to forced vital
capacity and FEV1 decreased.COPD is independently associated with hypertension,
and this could explain the link between the risk of cardiovascular diseases and
COPD.
PMID- 28489761
TI - Quality of life in adolescent patients with idiopathic scoliosis after brace
treatment: A meta-analysis.
AB - BACKGROUND: Whether brace-treated adolescents with idiopathic scoliosis (AIS)
have improved quality of life (QoL) is still unknown. Thus, we conducted a meta
analysis to compare the QoL of brace-treated AIS patients with untreated AIS
patients. The pain, self-image/appearance, mental health, function/activity,
satisfaction with management, total score without satisfaction, and total score
of patients were used to measure the QoL after the intervention. METHODS:
Multiple electronic databases including PubMed, Web of Science, and Embase were
searched for all years up to June 30, 2016. Articles in English that used the
Scoliosis Research Society-22 (SRS-22) or a modified version of the SRS-22
questionnaire to evaluate the QoL differences between brace-treated AIS patients
and untreated AIS patients were included in the meta-analysis. The Newcastle
Ottawa Scale was used in the quality of literature evaluation. The pooled
standardized mean difference (SMD) with its corresponding 95% confidence interval
(CI) for each parameter was computed. Egger test and Begg test were used to test
for publication bias. RESULTS: The SRS-22 or a modified SRS-22 questionnaire was
used to evaluate the QoL after surgery. There was no significant difference in
pain (SMD = 0.123, 95% CI: -0.101 to 0.347, P = .282), self-image/appearance (SMD
= 0.108, 95% CI: -0.116 to 0.332, P = .334), mental health (SMD = 0.031, 95% CI:
0.130 to 0.201, P = .365), function/activity (SMD = 0.202, 95% CI: -0.022 to
0.425, P = .077), and total score without satisfaction (SMD = 0.123, 95% CI:
0.232 to 0.478, P = .497) between the untreated (observation) and brace-treated
AIS patients, whereas a significant difference was observed in satisfaction with
management (SMD = 0.393, 95% CI: 0.127-0.659, P = .004) and total score (SMD =
0.312, 95% CI: 0.054-0.571, P = .018) between the 2 groups. CONCLUSION: Our meta
analysis indicated that brace-treated AIS patients had a higher QoL. However,
further analysis could not be performed because of insufficient data, such that
we were unable to make subgroup analysis of QoL for different types of AIS and
the therapeutic methods chosen by brace-treated AIS patients.
PMID- 28489762
TI - Comparison of local infiltration analgesia and sciatic nerve block as an adjunct
to femoral nerve block for pain control after total knee arthroplasty: A
systematic review and meta-analysis.
AB - BACKGROUND: To perform a meta-analysis to assess the efficiency and safety
between local infiltration analgesia (LIA) and sciatic nerve block (SNB) when
combined with femoral nerve block (FNB) for pain control following total knee
arthroplasty (TKA). METHODS: We systemically searched the following electronic
databases for potentially relevant articles: Embase (1980-2017.01), Medline (1966
2017.01), PubMed (1966-2017.01), ScienceDirect (1985-2017.01), web of science
(1950-2017.01) and the Cochrane Library. Only studies published in English that
were accessible online were considered. Furthermore, we only considered studies
that were published from 1966 to 2017. Only studies that met the following
inclusion criteria were considered: (a) patients were adult human subjects who
were set to undergo TKA; (b) the intervention was either SNB combined with FNB or
LIA combined with FNB; (c) the outcomes of the studies, such as visual analog
scale (VAS) scores, morphine consumption, length of stay and postoperative
adverse effects, including the risk of nausea, vomiting and falls, were reported;
(d) studies were either RCTs or non-RCT. Meta-analysis was performed using Stata
11.0 software. Modified Jadad score (7-points scale) which was based on Cochrane
Handbook for Systematic Reviews of Interventions is used for assessment of RCTs.
The Methodological Index for Nonrandomized Studies (MINORS) scale was used to
assess non-RCTs with scores ranging 0 to 24. The synthesis of the outcomes for
all studies was calculated as the weighted average rate by using a fixed or
random effect model which depends on statistical heterogeneity. Systematic review
registration number is CRD42017110661. RESULTS: Three randomized controlled
trials (RCTs) and 2 nonrandomized controlled trials (Non-RCTs), including 240
patients met the inclusion criteria. The present meta-analysis indicated that
there were significant differences between groups in terms of visual analog scale
(VAS) score at 12 hours (SMD = -0.337, 95% CI: -0.593 to -0.081, P =.010), VAS
score at 24 hours (SMD = -0.337, 95% CI: -0.612 to -0.061, P =.017), morphine
equivalent consumption at 24 hours (SMD = -0.371, 95% CI: -0.627 to -0.114, P =
.005) and incidence of nausea (RD = 0.215, 95% CI: 0.078 to 0.353, P = .002) and
vomiting (RD = 0.143, 95% CI: 0.026 to 0.260, P = .017). CONCLUSION: FNB combined
with SNB provided decreased VAS scores and less morphine consumption at 12 and 24
hours compared with FNB combined with LIA in total knee arthroplasty. In
addition, it was associated with lower risks of nausea and vomiting. We assessed
the quality of the evidence as low to very low; therefore, our confidence in the
effect estimate is limited, and the true effect may be substantially different
from our estimates. Further studies should focus on surgeries that are known to
be associated with significant postoperative pain, particularly surgeries where
improved pain control may deliver significant clinical benefits through reduced
morbidity, or cost-effectiveness benefits through faster rehabilitation and
discharge. The present meta-analysis has the following limitations: (1) only 5
studies were included in the meta-analysis. Although all of them are recently
published studies, the sample sizes are relatively small; (2) Functional outcome
is an important parameter; however, owing to the insufficiency of relevant data,
we failed to perform a meta-analysis on functional outcome; (3) The doses of
anesthetics and the concomitant pain management regimes varied between the
studies, which may have influenced the results; (4) The duration of follow-up was
relatively short, which might have led to an underestimating of complications;
and (5) publication bias present in the meta-analysis may have influenced the
results.
PMID- 28489763
TI - Naturally occurring drug resistance associated variants to hepatitis C virus
direct-acting antiviral agents in treatment-naive HCV genotype 1b-infected
patients in China.
AB - The direct-acting antiviral agents (DAAs) have drastically improved the prognosis
of hepatitis C virus (HCV) patients. However, the resistance-associated variants
(RAVs) to DAAs may hamper treatment. There was a lack of data on the prevalence
of pre-exist RAVs in Chinese HCV-infected patients. We performed nested PCR
assays on 74 HCV genotype 1b-infected patients to amplify HCV viral regions of
NS3, NS5A, and NS5B to investigate the prevalence of RAVs to DAAs in treatment
naive HCV genotype1b-infected patients in China. The mutations A156S, T54S, and
D168Y of the NS3/4A region were found in 18.33% (11/60), 6.67% (4/60), and 1.67%
(1/60) of the successfully amplified cases. Mutations Q30R, L31M, and H58P of the
NS5A region were confirmed in 57.63% (34/59), 1.69%(1/59), and 86.44% (51/59) of
the cases. Mutations C316N, S365A, M414L, M423I, Y448H, I482T, I482 V, V494L,
P495S, and V499A of the NS5B region were detected in 100% (60/60), 3.33% (2/60),
5.88% (3/51), 1.96% (1/51), 1.96% (1/51), 5.88% (3/51), 1.96% (1/51), 3.92%
(2/51), 5.88% (3/51), and 15.69% (8/51) of cases, respectively. Naturally
occurring RAVs to DAAs pre-exist in treatment-naive Chinese HCV genotype 1b
infected patients and the characteristic is different from that in Europe and the
United States. Clinicians should consider RAVs upon the introduction of DAA-based
antiviral therapy.
PMID- 28489764
TI - Mutual associations between intellectual disability and epilepsy-related
psychiatry disability: Population-based study.
AB - Epilepsy is the third-leading cause of psychiatry disability in China, and
intellectual disability (ID) is also 1 major type of disabilities in China. This
study estimates the prevalence of comorbidities with ID and epilepsy-related
psychiatry disability (EPD) and examines mutual associations within ID and
EPD.Data were taken from the Second China National Sample Survey on Disability,
which was a nationally representative, population-based survey. To derive a
nationally representative sample, the survey used multistage, stratified, cluster
random sampling with probability proportional to size. The disabled people who
had ID and EPD based on the World Health Organization International
Classification of Functioning, Disability, and Health and the International
Statistical Classification of Diseases. The cox-proportional hazards model was
used to examine the associations between ID and EPD considering the happened
sequence of ID and EPD.The prevalence of ID with EPD was 0.14 (95% confidence
interval: 0.09-0.19) per 1000 people. Age was strongly associated with the risk
of EPD, which was diagnosed after ID, especially among young ID population.
Except for age, other variables were also associated between ID and EPD
considering sequence of ID and EPD.This study is the first national study to
explore mutual associations with ID and EPD and highlights the young ID children
with high risk of development of epilepsy. To address the challenge of ID with
EPD disability in China, the government should adjust its strategies for
healthcare systems to prevent disability.
PMID- 28489765
TI - Anesthetic management of cesarean delivery in parturients with ruptured sinus of
Valsalva aneurysm: CARE-compliant 2 case reports and literature review.
AB - RATIONALE: Ruptured sinus of Valsalva aneurysm is rare and dangerous in
parturients. Few cases of ruptured SVA in pregnancy are reported, and the
anesthetic management for cesarean delivery has scarcely been described. PATIENT
CONCERNS: A parturient at 37-week gestation complained of a sore throat and cough
that started 3 days before admission, followed 1 day later by fever, dizziness,
breathlessness, and palpitation on exertion. Case two at 36-week gestation
complained of a 1-day history of bloating in the lower abdomen. DIAGNOSES: Full
term and preterm parturients with ruptured sinus of Valsalva aneurysm.
INTERVENTIONS: Cesarean deliveries were performed with incremental epidural
anesthesia technique under invasive monitoring. Surgical correction of the
ruptured sinus of Valsalva aneurysms and ventricular septal defect were performed
uneventfully 13 days and 7 days postpartum, respectively, for the 2 cases.
OUTCOMES: No complications were observed in the intra- or postoperative period
for both mothers and babies. LESSONS: We reviewed the pertinent literature and
reached the following conclusions: use of a multidisciplinary team to guide
anesthetic management is helpful and necessary; and both general anesthesia and
incremental epidural anesthesia can be safely used in parturients with ruptured
sinus of Valsalva aneurysm.
PMID- 28489766
TI - Sex difference determined the role of sex hormone-binding globulin in obese
children during short-term weight reduction program.
AB - The relationship between hyperinsulinemia and decreased sex hormone-binding
globulin (SHBG) levels has been observed in obese adults and children. Weight
reduction not only increased insulin sensitivity but also elevated serum SHBG
levels in obese adults and children. However, the correlation between the changes
in insulin resistance indices and serum SHBG concentration during weight
reduction program (WRP) is not fully understood, particularly in obese children.
This study is to evaluate whether SHBG level is a potential biomarker that can be
used to assess insulin resistance in obese children during a short-term WRP.
Forty-eight obese Taiwanese children (11.7 +/- 2.2 years; 25 boys and 23 girls)
participating in 8-week WRP were studied. Anthropometric measurements, lipid
profiles, insulin resistance indices, and serum SHBG concentration were recorded
at baseline and at the end of the WRP. The results showed body weight (BW), body
mass index (BMI), body fat percentage (BF%), body fat weight (BFW), and insulin
resistance indices such as fasting insulin, fasting insulin to glucose ratio,
homeostasis model assessment (HOMA) of insulin resistance, log (HOMA) all
significantly decreased after the 8-week WRP. With respect to lipid profiles,
only high-density lipoprotein cholesterol (HDL-C) levels increased in both sexes.
At baseline, insulin resistance indices were inversely correlated with SHBG
concentrations in girls, but not in boys. The difference in SHBG after WRP was
2.58 nmol/L (95% confidence interval [CI]: -3.51, 8.66) in boys and 0.58 nmol/L
(95% CI: -5.23, 6.39) in girls. There was a trend toward increased serum SHBG
levels in boys (P = .39) and girls (P = .84) after weight loss, but a
significantly negative correlation between the change in SHBG and in each of the
insulin resistance indices only in the girls after adjusting age and DeltaBFW
during WRP.In conclusion, short-term WRP has the potential effects of decreased
BW, BMI, BF%, and BFW, as well as increased serum HDL-C levels and insulin
sensitivity in obese Taiwanese children. Although serum SHBG levels moderately
increased in both sexes during short-term WRP, measuring the change in SHBG
concentrations might be a potential biomarker to evaluate improvement in insulin
resistance in girls only, and not in boys.
PMID- 28489768
TI - Prevalence of comorbidities in chronic obstructive pulmonary disease patients: A
meta-analysis.
AB - BACKGROUND: This study compares the prevalence rates of comorbidities between
chronic obstructive pulmonary disease (COPD) and non-COPD control patients
reported in literature. METHOD: Literature was searched in several electronic
databases. After the selection of studies by following precised eligibility
criteria, meta-analyses of odds ratios (ORs) were carried out with subgroup and
sensitivity analyses under random effects model. RESULTS: Eleven studies
(47,695,183 COPD and 47,924,876 non-COPD control patients' data) were used for
meta-analysis. Average age of COPD patients was 66.66 +/- 8.72 years of whom 55.4
+/- 11.9% were males. The prevalence of cardiovascular comorbidities [OR 1.90,
95% confidence interval (95% CI) 1.59-2.28; P < .00001], cerebrovascular
comorbidities (OR 1.84, 95% CI 1.47-2.31; P < .00001), hypertension (OR 1.45, 95%
CI 1.31-1.61; P < .00001), diabetes mellitus (OR 1.22, 95% CI 1.07-1.38; P =
.003), neurological and psychiatric disorders (OR 1.78, 95% CI 1.48-2.14; P <
.00001), gut and renal disorders (OR 1.96, 95% CI 1.43-2.68; P < .00001),
musculoskeletal disorders (OR 1.51, 95% CI 1.27-1.78; P < .00001), non-COPD
respiratory comorbidities (OR 2.81, 95% CI 2.52-3.14; P < .00001), and cancer (OR
1.67, 95% CI 1.25-2.23; P = .0005) were significantly higher in COPD patients
than in non-COPD controls. CONCLUSION: COPD is associated with significantly
higher comorbidities than in other diseases that should be taken into
consideration in COPD control strategies.
PMID- 28489767
TI - The association between hepatitis B mutants and hepatocellular carcinoma: A meta
analysis.
AB - BACKGROUND: More and more studies focus on the relationship between hepatitis B
virus (HBV) basal core promoter/precore (BCP/PC) mutations, but it remains
controvercial, we conducted a meta-analysis to investigate the features of
hepatitis B virus basal core promoter/precore mutations on the progression of
hepatocellular carcinoma (HCC). METHODS: A comprehensive search was conducted for
articles published between January 1, 2005 and December 31, 2015 using the
following databases: PubMed, Embase, Cochrane Library, Wanfang, and China
National Knowledge Infrastructure. Medical subject heading terms were prioritized
in setting the search strategy. Search terms included ("hepatitis B virus"),
("mutation or mutations or mutant"), and ("hepatocellular carcinoma" or "liver
cancer" or hepatoma). A meta-analysis of pooled results from case-control studies
examined the association between mutations G1896A, A1762T, G1764A, and
A1762T/G1764A and the risk of HCC. RESULTS: We included 29 articles for analysis
and found that G1896A (summary odds ratios [OR] = 2.04, 95% confidence interval
[CI] = 1.41-2.95), A1762T (summary OR = 3.96, 95% CI = 1.98-7.92), G1764A
(summary OR = 3.48, 95% CI = 1.99-6.09), and A1762T/G1764A (summary OR = 3.96,
95% CI = 2.77-5.65) are each associated with a statistically significant increase
in the risk of HCC. CONCLUSION: In summary, we found that G1896A, A1762T, G1764A,
and A1762T/G1764A are associated with an increased risk of HCC.
PMID- 28489769
TI - Retroperitoneal metastatic poorly differentiated carcinoma with beta-human
chorionic gonadotropin secretion presenting as a psoas abscess: A case report and
review of the literature.
AB - RATIONALE: Psoas abscesses generally arise from a contiguous intra-abdominal or
pelvic infectious process or hematogenous spreading of bacteria. The serum beta
human chorionic gonadotropin has been used to detect normal or ectopic pregnancy.
It also can be utilized in following up carcinomas. PATIENT CONCERNS: Here, we
reported a case of a 47-year-old woman who presented with a left psoas mass
presumptively diagnosed as an abscess secondary to lumbar tuberculosis In
addition, the patient had abnormal increase of beta-human chorionic gonadotropin.
The computed tomography (CT) scan and magnetic resonance imaging (MRI) showed
that the 5th lumbar vertebral infection or tuberculosis with left psoas abscess.
CT-guided percutaneous biopsy, surgical exploration and biopsy, and F-FDG
(fluorodeoxyglucose) positron emission tomography-CT (PET-CT) were used to make a
definite diagnosis. The sigmoidoscopy and biopsy were used to further diagnose.
DIAGNOSES: The biopsy of left psoas demonstrated metastatic or infiltrating
poorly differentiated carcinoma with secretion of beta-human chorionic
gonadotropin. The subsequent pathological examination of neoplasm showed the same
pathologic morphology. INTERVENTIONS: Appropriate treatment of infected
retroperitoneal mass, systematic chemotherapy and cancer biotherapy for
metastatic poorly differentiated carcinoma were taken. OUTCOMES: Interventions
provided little help until the patient died of secondary infection and multiple
organ failure. LESSONS: This case represents an extremely unusual clinical
presentation of metastatic poorly differentiated carcinoma with secretion of beta
human chorionic gonadotropin presenting as a psoas abscess. Physicians also need
to sharpen their awareness of the potential malignant carcinomas mimicking psoas
abscess.
PMID- 28489770
TI - Degeneration of corticofugal fibers in a patient with primary progressive
freezing gait: A case report.
AB - RATIONALE: To report a patient with primary progressive freezing gait (PPFG)
whose degeneration of corticofugal tract (CFT) from the supplementary motor area
(SMA) was demonstrated using diffusion tensor tractography (DTT). PATIENT
CONCERNS: A 66-year-old woman presented with a solitary symptom of a sudden
transient break on walking (i.e., freezing gait), which slowly progressed for 4
years. DIAGNOSES: Imaging evidence using magnetic resonance imaging and F
florinated-N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-lodophenyl)
nortropane positron emission tomography scanning was unremarkable, and our
patient's symptom was not affected by dopamine agonist medication. Based on the
clinical symptoms and imaging findings, we diagnosed our patient as having PPFG.
INTERVENTIONS: From the patient and 20 age- and sex- matched normal controls,
diffusion tensor imaging data were acquired using a 1.5 T magnetic resonance
scanner. OUTCOMES: In DTT findings, the CFT from the left SMA was partially torn
and thinned. Moreover, the fractional anisotropy value and tract volume of CFT
from the left SMA were more than two standard deviations lower than those of
normal controls. LESSONS: In our opinion, the lesion in the CFT from the left SMA
in our patient was attributed to the occurrence of PPFG. We believe that the
results of this study suggest one of the pathological mechanisms for the
occurrence of gait difficulty in PPFG.
PMID- 28489771
TI - Chronic active Epstein-Barr virus infection associated with hemophagocytic
syndrome and extra-nodal natural killer/T-cell lymphoma in an 18-year-old girl: A
case report.
AB - RATIONALE: Chronic active Epstein-Barr virus infection (CAEBV) associated with
hemophagocytic syndrome (HPS) and extra-nodal natural killer (NK)/T-cell lymphoma
(ENKL) is a rare life-threatening disorder. This disease is easily misdiagnosed
because of its varied presentations. PATIENT CONCERNS: An 18-year-old girl was
admitted to our hospital with a history of edema in the lower limbs and
intermittent fever lasting for more than 1 month. At admission, she had severe
liver injury of unknown etiology. Laboratory test results revealed pancytopenia,
hyperferritinemia, hypertriglyceridemia, and hypofibrinogenemia. Results of
serologic tests for EBV were positive. Results of a skin biopsy indicated EBV
positive NK/T-cell lymphoma, and bone marrow aspiration revealed focal
hemophagocytosis and atypical lymphoid cells. DIAGNOSIS: On the basis of these
findings, we diagnosed the case as extra-nodal NK/T-cell lymphoma-associated HPS
(natural killer/T-cell lymphoma-associated hemophagocytic syndrome), which is
commonly induced by CAEBV. INTERVENTIONS: Treatment consisted of general
management of hepatitis, supplemented with albumin and empirical antibiotic
therapy. OUTCOMES: The patient died from massive gastrointestinal hemorrhage a
week after she was discharged from the hospital. LESSONS: ENKL and HPS present
with varied features and are generally fatal; therefore, clinicians should
proceed with caution in suspected cases. HPS should be considered when the
patient presents with fever, hepatosplenomegaly, pancytopenia, and liver failure.
When HPS is suspected, clinicians should determine the underlying cause, such as
severe infection, including infection with viruses such as EBV; genetic
predisposition; or underlying malignancies, especially lymphoma because of its
strong association with HPS.
PMID- 28489772
TI - Primary diffuse large B cell lymphoma of the uterine cervix successfully treated
by combined chemotherapy alone: A case report.
AB - RATIONALE: Primary lymphomas of the uterine cervix are a rare disease. They are
often misdiagnosed because of their rarity and because they can be easily
confused with a squamous cell carcinoma of the cervix, as they are usually
presented as exophytic mass with vaginal bleeding as their most common symptoms.
Nevertheless, considering that both the prognosis and the treatment are
completely different between them, differential diagnosis should be taken into
account. PATIENT CONCERNS: A case of a 51-year-old woman with a primary diffuse
large B-cell lymphoma of the cervix is presented. DIAGNOSES: Diagnosis of this
tumor was a challenge for pathologists and clinicians, as four biopsies were
needed to achieve a final diagnosis. INTERVENTIONS: Patient was successfully
treated with combined Rituximab and chemotherapy (R-CHOP) alone. OUTCOMES:
Complete remission, confirmed through biopsy, was reached after six courses of
chemotherapy. At 2-years follow up, patient is alive and free of disease.
LESSONS: Considering that the prognosis and treatment of primary malignant
lymphoma of the cervix are completely different than that of the squamous cell
carcinoma, awareness of this disease should be considered in the differential
diagnosis.
PMID- 28489773
TI - CT analysis of anatomical variation and injury affecting posterior pedicle screw
fixation for unstable Hangman fractures.
AB - The aim of this study was to evaluate the anatomical variations and injuries in
patients with unstable Hangman fractures that affected the posterior pedicle
screw placement of C2 to C3 and retrospectively review our experience with
management of these fractures. Clinical data were reviewed in 72 patients with
unstable Hangman fractures, especially using 3-dimensional computed tomography
(3D-CT) scan to identify the presence of anatomical variations or injuries and
analyzing the treatment strategies we used. Twenty-two patients (22/72, 30.6%)
with 39 (C2 or C3) risk factors were not fit for safe C2 to C3 pedicle screw
placement, due to factors such as small pedicle size of C2 or C3, high-riding
vertebral arteries, fractured fragments encased into vertebral canal, or
transverse process foramen of C2, sclerotic pedicles and pedicle fractures of C3.
One or more than one of these risk factors could pose more risks of arterial or
neural structures damages to pedicle screw fixation for unstable Hangman
fractures. Individualized treatment plans were made to minimize the risks of
surgery for the 22 patients. There is a high incidence of anatomical variations
and injuries in the C2 to C3 region in patients with unstable Hangman fractures
that affect the pedicle screw placement. Preoperative evaluation of these
conditions using 3D-CT scans is of paramount importance to avoid and decrease
operative complications and to choose appropriate surgical techniques.
PMID- 28489774
TI - Prognostic impact of C-reactive protein/albumin ratio on the overall survival of
patients with advanced nonsmall cell lung cancers receiving palliative
chemotherapy.
AB - Recent studies have indicated that the C-reactive protein (CRP)/albumin (CRP/Alb)
ratio is associated with clinical outcomes in patients with various carcinomas.
However, no studies have explored the association between the ratio of CRP/Alb
and clinical outcome of inoperable patients with nonsmall cell lung cancers
(NSCLCs). We examined the prognostic impact of CRP/Alb ratio on 165 stage IV
NSCLC receiving palliative chemotherapy. The optimal cutoff level of CRP/Alb
ratio was set at 0.195. The median follow-up time was 9 months (range, 1-74
months). On univariate analysis, high CRP/Alb ratio (>=0.195) was correlated (P <
.001) with poorer overall survival (OS). Subgroup analysis of adenocarcinoma
showed that CRP/Alb ratio was significantly (P < .001) associated with OS.
Multivariate analysis showed that CRP/Alb ratio was an independent prognostic
factor for OS (hazard ratio: 2.227, P = .001). Subgroup analysis revealed that
the CRP/Alb ratio had a significant (P = .001) prognostic impact on
adenocarcinoma patients receiving platinum chemotherapy. Elevated CRP/Alb ratio
was significantly associated with male gender (P = .002) and smoking history (P =
.009). The results of this study suggest that the CRP/Alb ratio might be used as
a simple, inexpensive, and independent prognostic factor for OS of patients with
advanced lung adenocarcinomas receiving platinum chemotherapy.
PMID- 28489775
TI - Effects of nimodipine on postoperative delirium in elderly under general
anesthesia: A prospective, randomized, controlled clinical trial.
AB - Nimodipine is a clinical commonly used calcium antagonistscan lowering the
apoptosis rate of hippocampal neuron to reduce the incidence of postoperative
cognitive dysfunction (POCD). This study was designed to evaluate the effects of
nimodipine on postoperative delirium in elderly under general anesthesia.Sixty
patients shceduced spine surgery under general anesthesia were randomly assigned
into 2 groups using a random number table: control group (Group C) and nimodipine
group (Group N). In Group N, nimodipine 7.5 MUg/(kg * h) was injected continually
30 minutes before anesthesia induction, while the equal volume of normal saline
was given in Group C. At 0 minute before injection, 0 minute after tracheal
intubation, 1 hour after skin incision and surgery completed (T1-4), blood
samples were taken from the radial artery and jugular bulb for blood gas
analysis. Cerebral oxygen metabolism-related indicators were calculated at the
same time. Concentration of S100beta and glial fibrillary acidic protein (GFAP)
were tested by ELISA. The incidence of postoperative delirium within 7 days after
surgery was recorded.Cerebral oxygen metabolism-related indicators fluctuationed
in the normal range in 2 groups at different time points and the difference were
not statistically significant. Compared with Group C, S100beta and GFAP decreased
and incidence of postoperative delirium reduced at T3-4 in Group N, the
difference was statistically significant (P<.05).The present study suggests that
nimodipine can reduce the development of postoperative delirium in elderly
patients under general anesthesia, the reduction of brain injury and improvement
of cerebral oxygen metabolism may be involved in the mechanism.
PMID- 28489776
TI - Is C-reactive protein a marker of obstructive sleep apnea?: A meta-analysis.
AB - BACKGROUND: Obstructive sleep apnea (OSA) is a common disease, distinguished by
recurrent episodes of upper airway obstruction during sleep, with an inflammatory
component. C-reactive protein (CRP) and high-sensitivity C-reactive protein (hs
CRP) are markers of systemic inflammation and may serve as biomarkers of OSA.
METHODS: Scientific studies published from January 1, 2006, to January 1, 2016
were obtained via searches of PubMed, Embase, SCI, and China National Knowledge
Internet (CNKI) using relevant terms. Studies concerning serum CRP level/ hs-CRP
in OSA patients were reviewed by 2 independent reviewers. Studies were included
if they conform with our specific criteria of inclusion. Eligible studies were
subjected to quality review, data extraction, and meta-analysis by using RevMan
(version 5.2) and STATA (version 12.0). RESULTS: There were 15 studies that met
inclusion criteria that included a total of 1297 subjects. Meta-analysis revealed
that serum CRP levels in the OSA group were 1.98 mmol/L higher than those in
control group (95% confidence interval: 1.39-2.58, P < .01). Similarly, serum hs
CRP levels in the OSA group were 1.57 mmol/L higher than that in the control
group (95% confidence interval: 0.96-2.18, P < .01). Subgroup analysis showed
greater differences between OSA patients and controls in the setting of obesity
(body mass index)> = 30. The total weighted mean difference (WMD) between OSA and
controls within the subgroup of subjects who had a CRP was 2.10; for hs-CRP, the
WMD was 2.49. Comparing OSA patients of mean apnea hypopnea index> = 15 and
controls, the total WMD for the CRP subgroup was 2.19; for the hs-CRP subgroup,
the WMD was 1.70. CONCLUSION: In our meta-analysis, serum CRP/hs-CRP levels were
discovered to be higher in OSA patients compared with control subjects. Those
with higher body mass index and apnea hyponea index demonstrated larger
differences in CRP/hs-CRP levels. These data are consistent with an inflammatory
component of OSA pathophysiology and support the role of CRP/hs-CRP as a
biomarker in this disease.
PMID- 28489777
TI - Affective temperament does not influence satisfaction after total knee
arthroplasty.
AB - BACKGROUND: Inherent temperament of the patient may predict the outcome of the
surgical procedure. The purpose of this study was to ascertain whether negative
affective temperament affects patient satisfaction and outcome measures. METHODS:
This prospective study included 143 patients who underwent total knee
arthroplasty for primary arthrosis. Preoperatively, the Memphis, Pisa, Paris and
San Diego-Auto questionnaire was used to define the temperament of the patient.
Knee Society Score (KSS) and short form-36 (SF-36) outcome measures were used to
evaluate the functional outcome. RESULTS: No relationship was determined between
temperament and satisfaction (P = .734). Overall, the satisfaction rate of the
procedure in our patients was 93%. The KSS improved from a mean of 47.9 to 70.1
(F = 124.275; P < .05) and the SF-36 physical component summary, and SF-36 mental
component summary scores improved to a mean of 39.5 and 43.04 points,
respectively. CONCLUSION: Temperament was not found to have any effect on patient
satisfaction. However, patient satisfaction was directly related to better
functional outcomes.
PMID- 28489779
TI - Epidural hematoma after total hip arthroplasty in ankylosing spondylitis patient:
A case report and review of the literature.
AB - RATIONALE: Ankylosing spondylitis (AS) can affect the hip joint, causing
deformity and disability. Total hip arthroplasty can obviously relieve the pain
of the hip joint, and reconstruct the function of hip joint. Epidural anesthesia
in this patient population has high risk of epidural hematoma, but the reason is
unclear. PATIENT CONCERNS: A 44-year-old man diagnosed with AS underwent total
hip arthroplasty. DIAGNOSES: Six days after operation, he was diagnosed epidural
hematoma. INTERVENTIONS: Laminectomy and decompression surgery was performed.
OUTCOMES: At the last follow-up, he recovered the feeling and function of lower
limbs. A literature review was undertaken to understand the incidence and risk
factors. The incidence of spinal hematoma in this population is high and only
probable risk factors are reported without further research. LESSONS: Based on
our review and the illustration of this case, AS patients have both lumbar and
hip bony fusion. The exact bone canal caused by the lumbar puncture needle may
play an important role in epidural hematoma. General anesthesia may be a better
choice for this special patient cohort.
PMID- 28489778
TI - Pancreatoduodenectomy (PD) and postoperative pancreatic fistula (POPF): A
systematic review and analysis of the POPF-related mortality rate in 60,739
patients retrieved from the English literature published between 1990 and 2015.
AB - BACKGROUND: Pancreatoduodenectomy (PD) is one of the most technically demanding
operations challenging surgeons, and a postoperative pancreatic fistula (POPF)
can complicate an otherwise uneventful postoperative (PO) course. This review
examined the methods and procedures used to prevent postoperative pancreatic
fistula (POPF) after pancreatoduodenectomy (PD). METHODS: A comprehensive
systematic search of the literature was performed using PubMed (Medline), Embase,
Web of science, and the Cochrane databases for studies published between January
1, 1990 and December 31, 2015. English language articles involving at least 100
patients undergoing PDs carried out in centers performing at least 10 PDs/y were
screened for data regarding the Grade of any POPFs according to the definition of
the International Study Group on Pancreatic Fistula (ISGPF) and the overall rate
of PO mortality related to POPF. RESULTS: We reviewed 7119 references through the
major databases, and an additional 841 studies were identified by cross-checking
the bibliographies of the full-text articles retrieved. After excluding 7379 out
of 7960 studies, because they did not meet the eligibility criteria, the full
texts of 581 articles were examined; 96 studies were excluded at this point,
because they concerned partially or totally duplicate data that had already been
reported. The remaining 485 articles were screened carefully for POPF-related
mortality and POPF Grades as defined by the ISGPF. Of the 485 articles, 208
reported the POPF-related PO mortality rate and 162 the Grades (A, B, and C) of
POPFs in 60,739 and 54,232 patients, respectively. The POPF-related mortality
rates after pancreatojejunostomy and pancreatogastrostomy were similar but were
less (0.5% vs. 1%; P = .014) when an externally draining, trans-anastomotic stent
was placed intraoperatively. The incidence of the different Grades of POPF Grade
was quite variable, but Grade C POPFs were associated with a PO mortality rate of
25.7% (range 0-100%). CONCLUSIONS: The POPF-related mortality rate has remained
at approximately 1% over the past 25 years. Only externally draining, trans
anastomotic stents decreased the POPF-related mortality rate. However, adequately
designed venting drains were never tested in randomized controlled trials (RCTs).
PMID- 28489780
TI - Prognostic and clinicopathological significance of cyclin B expression in
patients with breast cancer: A meta-analysis.
AB - BACKGROUND: Cyclin B plays a crucial role in cancer cell cycle progression and is
overexpressed in many human cancers, including breast cancer. However, the
prognostic value of cyclin B expression in breast cancer is controversial. We
performed a meta-analysis to assess the clinicopathological and prognostic
significance of cyclin B expression in breast cancer. METHODS: We searched
PubMed, web of science, and Embase databases to retrieve the publications
investigating the association between cyclin B expression and
clinicopathological/prognostic significance in breast cancer patients. The pooled
hazard ratio (HR) or odds ratio (OR) with its 95% confidence intervals (CIs) were
used to estimate the effects. RESULTS: Ten studies with 2366 breast cancer
patients were included to evaluate the association between cyclin B expression
and overall survival (OS), disease-free survival (DFS), disease-specific survival
(DSS), and clinicopathological parameters. The results showed that cyclin B
overexpression in breast cancer patients was significantly associated with both
poor OS (univariate analysis: HR = 2.38, 95% CI = 1.72-3.30, P < .001), DFS
(univariate analysis: HR = 1.86, 95% CI = 1.50-2.32, P < .001; multivariate
analysis: HR = 1.75, 95% CI = 1.22-2.52, P = .003), and DSS (multivariate
analysis: HR = 5.42, 95% CI = 2.15-13.66, P < .001). Additionally, cyclin B
overexpression was significantly associated with lymphatic invasion (OR = 2.58,
95% CI = 1.03-6.46, P = .017). CONCLUSION: Cyclin B overexpression appears to be
an independent potential prognostic marker to DSS and DFS for breast cancer.
Further studies with large sample size are needed to dissect the relationship
between cyclin B and clinicopathological features or prognosis of breast cancer.
PMID- 28489781
TI - Clinical characteristics and outcomes of patients with myocarditis mimicking ST
segment elevation myocardial infarction: Analysis of a case series.
AB - Acute myocarditis mimicking ST-segment elevation myocardial infarction (STEMI) is
highly deceptive for an accurate diagnosis, and a systematic study is lacking
with regard to the clinical features and prognosis of this distinct clinical
entity.Patients with suspected STEMI and eventually diagnosed with myocarditis by
cardiac magnetic resonance (CMR) from January 2012 to April 2016 at Fuwai
Hospital were identified by reviewing medical records and electronic databases.
Follow-up was conducted by clinical visits and phone contacts in a median
duration of 17 months.A total of 18 patients were included in the study, with 17
males and 1 female. They were relatively young, and their mean age was 30.8
years. 94.4% of the patients had a high prevalence of infectious prodrome, and
inflammatory biomarkers were notably elevated in all patients. Late gadolinium
enhancement on CMR was detected in 13 patients. Three patients underwent
fulminant course, and left ventricular ejection fraction (LVEF) <45% on admission
occurred in 3 patients. The median LVEF improved from 59% on admission to 65% at
discharge (P <.001), and none developed cardiac insufficiency, heart
transplantation, or death during a median follow-up of 17 months.Myocarditis
mimicking STEMI is featured by young age and an existence of flu-like prodrome.
CMR benefits the differential diagnosis of this unique clinical entity. Notably,
patients with myocarditis mimicking STEMI had a favorable prognosis, and
establishing an accurate diagnosis is crucial to avoid unreasonable treatments
for them.
PMID- 28489782
TI - Incidence and risk factors of depression after diagnosis of lung cancer: A
nationwide population-based study.
AB - This study aimed to explore the incidence and risk factors of depression after
lung cancer diagnosis. Using the Taiwan National Health Insurance Research
Database (NHIRD), incidences and risk factors of depression in lung cancer and
nonlung cancer cohorts were analyzed.From 1998 to 2006, a total of 22,125
patients were included in each matched cohort of lung cancer and nonlung cancer
patients from NHIRD. The incidence of depression was higher in the lung cancer
cohort than in the nonlung cancer cohort (1545.8 vs 1366.6 per 100,000 person
years). An increased risk of depression was observed in the lung cancer cohort
[adjusted hazard ratio (aHR): 1.16, 95% confidence interval (95% CI): 1.01-1.34,
P = .0377]. In lung cancer patients, age <=50 years (aHR: 2.72, 95% CI: 2.02
3.66, P < .0001), age 50 to 69 years (aHR: 2.34, 95% CI: 1.87-2.94, P < .0001),
female gender (aHR: 1.50, 95% CI: 1.26-1.80, P < .0001), coronary artery disease
(CAD) (aHR: 1.40, 95% CI: 1.08-1.82, P = .0113), and operation (aHR: 1.78, 95%
CI: 1.46-2.16, P < .0001) were associated with an increased risk of depression.
In addition, higher incidences of emergency room (ER) visit (4.76 vs 2.82, per
person-year) and admission (5.73 vs 4.33, per person-year) were observed in lung
cancer patients with depression than those without depression.Our results showed
that early surveillance and intervention of depression should be advocated after
a diagnosis of lung cancer.
PMID- 28489783
TI - Clinical significance and prognostic value of Triosephosphate isomerase
expression in gastric cancer.
AB - Triosephosphate isomerase (TPI) is highly expressed in many human cancers and is
involved in migration and invasion of cancer cells. However, TPI
clinicopathological significance and prognostic value in gastric cancer (GC) are
not yet well defined. The aim of the present work was to evaluate TPI expression
in GC tissue and its prognostic value in GC patients.TPI expression was analyzed
in 92 primary GC tissues and 80 adjacent normal mucosa tissues from GC patients
undergoing gastrectomy by immunohistochemical analysis of tissue microarrays
(TMAs). Univariate and multivariate analyses were performed to investigate TPI
prognostic significance in GC patients.Immunohistochemical staining score showed
that TPI expression in cancer tissues was significantly higher than in adjacent
normal mucosa (P < .001). Univariate analysis revealed that TPI expression, depth
of invasion, lympho node metastasis, tumor node metastasis (TNM) stage, and tumor
diameter were associated with negative prognostic predictors for overall survival
in GC patients (P < .05). High TPI expression represented a significant predictor
of shorter survival in GC patients with positive lymphatic metastasis (P = .022)
and tumor diameter >5 cm (P = .018). Cox multivariate analysis identified TPI
expression, TNM stage, and tumor diameter as independent prognostic factors in GC
patients.TPI expression might be considered as a novel prognostic factor to
evaluate GC patients' survival.
PMID- 28489784
TI - Rectal cancer: Short-term reproducibility of intravoxel incoherent motion
parameters in 3.0T magnetic resonance imaging.
AB - The aim of this study was to evaluate the short-term test-retest reproducibility
of diffusion-weighted magnetic resonance imaging (DW-MRI) parameters of rectal
cancer with 3.0T MRI.Twenty-six patients with rectal cancer underwent MRI,
including diffusion-weighted imaging with 8 b values. Apparent diffusion
coefficient (ADC) and intravoxel incoherent motion (IVIM) parameters (D, pure
diffusion; f, perfusion fraction; D*, pseudodiffusion coefficient) were,
respectively, calculated. The short-term test-retest reproducibility, the intra
and interobserver variation of the IVIM parameters were assessed based on the
repeatability coefficient and Bland-Altman limits of agreement.There was no
significant intra or interobserver difference observed in the parameters on the
same DW-MRI scan. The corresponding repeatability coefficient of intra- and
interobserver analysis for ADC, D, f, and D* was 5.4%, 11.1%, 55.4%, and 40.3%;
10.9%, 41.6%, 134.0%, and 177.6%, respectively. The test-retest repeatability
coefficient for ADC, D, f, and D* was 19.1%, 24.5%, 126.3%, and 197.4%,
respectively, greater than the intraobserver values.ADC and D have better short
term test-retest reproducibility than f and D*. Considering the poor test-retest
reproducibility for f and D,* variance in these 2 parameters should be
interpreted with caution in longitudinal studies on rectal cancer in which
treatment response and recurrence are monitored.
PMID- 28489785
TI - Effect of psoas muscle mass after endoscopic therapy for patients with esophageal
varices.
AB - We aimed to investigate the impact of decrease of muscle mass on survival after
eradication of esophageal varices (EVs) treated by endoscopic therapies as a
primary prophylaxis in patients with liver cirrhosis (LC). In all, 177 LC
individuals with EVs undergoing endoscopic therapies were analyzed. We
retrospectively examined the impact of muscle mass decrease as determined by
psoas muscle mass (PMM) at the third lumber on computed tomography (depletion of
PMM [DPMM]) on survival as compared with serum sodium combined Model for End
stage Liver Disease (MELD-Na). In comparison of the effects of these parameters,
we used time-dependent receiver-operating characteristics (ROC) analysis. We also
investigated parameters related to overall survival in the univariate and
multivariate analyses. This study included 116 males and 61 females with a median
age of 66 years. The median follow-up periods were 2.7 years (range 0.1-9.6
years). In all, 110 patients (62.1%) had DPMM. The median MELD-Na score was 7.200
(range -3.451 to 30.558). The MELD-Na score in patients with DPMM (median 7.685)
was significantly higher than that in patients without DPMM (median 6.235) (P =
.0212). In the multivariate analysis, presence of hepatocellular carcinoma (P <
.0001), presence of DPMM (P < .0001), and MELD-Na >=7.2 (P = .0438) were revealed
to be significant predictors related to overall survival. In time-dependent ROC
analyses, all area under the ROCs for DPMM in each time point were higher than
those for MELD-Na in the entire cohort and in patients without hepatocellular
carcinoma at baseline (n = 133). In conclusion, for LC patients treated by
endoscopic therapies for EVs, DPMM had stronger prognostic impact than MELD-Na.
PMID- 28489786
TI - Bilateral carotid-cavernous fistula with spontaneous resolution: A case report
and literature review.
AB - RATIONALE: Bilateral carotid-cavernous fistula (CCF) is rare and serious extra
ocular disease occurring in clinical which may result in severe complication.
Unique manifestations and imaging examinations are important to the diagnosis.
PATIENT CONCERNS: A case of bilateral carotid-cavernous fistula in an 60-year-old
healthy man caused by a head injury is reported. Further clinical symptoms and
signs and imaging examinations lead to the correct diagnosis. DIAGNOSES: Computed
tomography angiography of the brain aroused suspicion of bilateral CCF. On
physical examination, intraocular pressure in the right eye was 35 mm Hg, while
the other eye was 56 mm Hg. INTERVENTIONS: After diagnosis, the patient chose
conservative treatment for some reasons. OUTCOMES: The symptom of him had
relieved in both eyes but no light perception in the right eye after two months
telephone follow-up. LESSONS: Our case study demonstrated that a highly suspicion
must be maintained when managing such patients to prevent serious consequences.
At the same time, the early diagnosis and treatment of the disease have a
critical relationship to the prognosis of patients, which should be paid
attention to.
PMID- 28489787
TI - A systematic review and meta-analysis of intravenous glucocorticoids for acute
pain following total hip arthroplasty.
AB - BACKGROUND: Glucocorticoids are increasingly used perioperatively, principally to
prevent postoperative nausea and vomiting (PONV), and acute postoperative pain
following total hip arthroplasty (THA). The authors hypothesized that
preoperative intravenous glucocorticoids is associated with less pain scores and
PONV without increasing the complications after THA. METHODS: Four databases
(PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of
Science) were searched with the limitations of randomized controlled trials
(RCTs). The search cutoff date was set at November 6, 2016. Participants were
patients who were prepared for primary THA. Intervention was preoperative
intravenous glucocorticoids for postoperative pain control. Outcomes including
the visual analog scale (VAS) scores at the postanesthesia care unit (PACU) and
at 24 and 48 hours post operation, the occurrence of PONV and total morphine
consumption were recorded. We calculated risk ratio (RR) with a 95% confidence
interval (CI) for dichotomous outcomes, and the weighted mean difference (WMD)
with a 95% CI for continuous outcomes. RESULTS: A total of 6 studies were
evaluated, which included 297 patients who underwent hip surgery with intravenous
glucocorticoid treatment and control patients who underwent hip surgery without
glucocorticoid treatment. Pooled results indicated that intravenous
glucocorticoid treatment was associated with a reduction of VAS scores at the
PACU (WMD = -9.06, 95% CI -12.67 to -5.45, P = .000) and total morphine
consumption by 15.68 mg (WMD = -15.68, 95% CI -24.60 to -6.75, P = .001). No
significant difference was observed in the VAS scores at 24 and 48 hours between
the intravenous glucocorticoid and placebo treatments. Intravenous steroids can
decrease the occurrence of PONV (RR = 0.46, 95% CI 0.26-0.82, P = .029).
CONCLUSION: Intravenous glucocorticoid treatment can decrease early pain
intensity and PONV after THA. However, the evidence for the use of
glucocorticoids is limited by the low number of studies and variation in dosing
regimens. Thus, additional high-quality RCTs are needed to identify the optimal
drug protocol and determine the safety of intravenous glucocorticoids.
PMID- 28489788
TI - Cytomegalovirus retinitis in a patient with secondary acute lymphosarcoma
leukemia undergoing allogeneic hematopoietic stem-cell transplantation: A rare
case report: a care-compliant article.
AB - RATIONALE: Cytomegalovirus (CMV) retinitis is a common opportunistic infection in
immunocompromised patients, which may lead to blindness. CMV retinitis is not an
uncommon infectious disease in patients with immune regulatory abnormalities, for
example, human immunodeficiency virus (HIV) patients. However, CMV retinitis in a
patient with acute lymphosarcoma leukemia (ALL) undergoing allogeneic
hematopoietic stem-cell transplantation (HSCT) phase is very rare. PATIENT
CONCERNS: A case of CMV retinitis in a patient receiving immunosuppressive
therapy as a part of ALL allogeneic HSCT is described including the pathogenesis,
clinical signs, and therapy. DIAGNOSES: CMV retinitis. INTERVENTIONS: Ganciclovir
intravitreal injection at weekly intervals for 4 weeks. OUTCOMES: Patient's
vision had improved and the load of CMV deoxyribonucleic acid (DNA) in the
aqueous humor declined. The CMV retinitis and perivascular of retina infiltration
regressed. LESSONS: We propose that the concentration of CMV DNA load in the
aqueous humor could be useful in making the diagnosis and in selecting the
optimal treatment in this kind of CMV retinitis.
PMID- 28489789
TI - Effective and extensible feature extraction method using genetic algorithm-based
frequency-domain feature search for epileptic EEG multiclassification.
AB - In this paper, genetic algorithm-based frequency-domain feature search (GAFDS)
method is proposed for the electroencephalogram (EEG) analysis of epilepsy. In
this method, frequency-domain features are first searched and then combined with
nonlinear features. Subsequently, these features are selected and optimized to
classify EEG signals. The extracted features are analyzed experimentally. The
features extracted by GAFDS show remarkable independence, and they are superior
to the nonlinear features in terms of the ratio of interclass distance and
intraclass distance. Moreover, the proposed feature search method can search for
features of instantaneous frequency in a signal after Hilbert transformation. The
classification results achieved using these features are reasonable; thus, GAFDS
exhibits good extensibility. Multiple classical classifiers (i.e., k-nearest
neighbor, linear discriminant analysis, decision tree, AdaBoost, multilayer
perceptron, and Naive Bayes) achieve satisfactory classification accuracies by
using the features generated by the GAFDS method and the optimized feature
selection. The accuracies for 2-classification and 3-classification problems may
reach up to 99% and 97%, respectively. Results of several cross-validation
experiments illustrate that GAFDS is effective in the extraction of effective
features for EEG classification. Therefore, the proposed feature selection and
optimization model can improve classification accuracy.
PMID- 28489790
TI - CA125 modified by PLT and NLR improves the predictive accuracy of adenomyosis
derived pelvic dense adhesion.
AB - To explore the value of serum levels of CA125, platelet count (PLT), neutrophil
lymphocyte ratio (NLR), and modified CA125 markers CA125a and CA125b in
predicting pelvic dense adhesion (PDA) associated with adenomyosis, CA125a =
lg(CA125 * PLT * 10), CA125b = lg(CA125 * NLR).This retrospective study included
304 patients who underwent surgery for adenomyosis. Correlations of serum levels
of CA125, PLT, NLR, and modified CA125 markers with adenomyosis-derived PDA were
analyzed by Logistic regression. Receiver operating characteristic curve was
applied to assess the utility of these parameters for predicting PDA.All the
parameters including CA125, PLT, NLR, and modified CA125 markers were positively
correlated with PDA (P < .05 or P < .01). More importantly, CA125a was more
specific (85.03% vs. 83.00%) and more sensitive (47.56% vs. 47.47%) than CA125
alone for the prediction of PDA, and CA125b could also improve the predictive
specificity of PDA (53.13% vs. 47.47%).Serum CA125, PLT, and NLR were all closely
correlated with PDA in adenomyosis patients. CA125 modified by PLT and NLR could
further improve the predictive accuracy of adenomyosis-derived PDA, thus
providing more meaningful references for better-informed decisions about the mode
of surgical access for the clinical treatment of adenomyosis.
PMID- 28489791
TI - Effect of perioperative statin therapy on renal outcome in patients undergoing
cardiac surgery: A meta-analysis of randomized controlled trials.
AB - BACKGROUND: Acute renal injury (AKI) is a common renal complication after cardiac
surgery. The aim of this study was to determine the effect of perioperative
statin therapy (PST) on postoperative renal outcome in patients undergoing
cardiac procedures. METHODS: We searched for the reports that evaluating the
effect of PST on renal outcomes after cardiac surgery between March 1983 and June
2016 in the electronic database Cochrane Central Register of Controlled Trials
(CENTRAL), MEDLINE/PubMed, and EMBASE/OVID. RESULTS: Nine randomized controlled
trials (RCTs) enrolling 2832 patients, with 1419 in the PST group and 1413 in the
control group, were included in this meta-analysis. Our results suggested that
PST increased the incidence of postoperative renal complication (relative risk
[RR] 1.18, 95% confidence interval [CI] 1.01-1.36, P = .03) with low
heterogeneity (I = 30%, P = .18). Six studies with 3116 patients detected no
significant difference in severe renal complication between PST and control
groups (RR 1.23, 95%CI 0.84-1.79, P = .28). Postoperative serum creatinine (sCr)
at 48 hours was shown to be higher in the PST group (mean difference [MD] 0.03,
95% CI 0.03-0.03; P < .01). The length of hospital stay was decreased slightly by
0.59 day in the PST group (95% CI -0.85 to -0.33; P < .01). CONCLUSIONS:
Perioperative statin therapy seems to jeopardize short-term renal outcome in
patients undergoing cardiac surgery, but the occurrence of severe renal
complication was not affected.
PMID- 28489792
TI - Eye bank prepared versus surgeon cut endothelial graft tissue for Descemet
membrane endothelial keratoplasty: An observational study.
AB - The purpose of this article is to examine outcomes of Descemet membrane
endothelial keratoplasty (DMEK) performed with cornea bank (CB) prestripped
tissue and surgeon stripped tissue (SST).This retrospective study examined
subjects who underwent DMEK with CB or surgeon prepared tissue for Fuchs
endothelial corneal dystrophy. Best-corrected visual acuity (BCVA), corneal
thickness, endothelial cell count (ECC), and complications were examined before
and throughout a 6-month postoperative period.Eleven CB and 22 SST subjects were
included. Six months after surgery, BCVA was 20/20 or better in 36.4% of CB and
22.7% of SST subjects (P = .43). Median logMAR BCVA was 0.10 (0.00-0.20, 20/25)
in group CB and 0.10 (0.10-0.30, 20/25) in group SST. Median preoperative corneal
thickness was 614.0 MUm (577.5-662.0 MUm) and 658.0 MUm (606.0-689.0 MUm) in CB
and SST subjects, respectively (P = .37). Six months after surgery, median
corneal thickness was lower in the CB group (571.0 MUm [478.0-592.0 MUm]), than
in the SST group (576.0 MUm [531.0-607.0 MUm], P = .02). At 6 months, median ECC
was 1500.0 cell/mm (1321.5-2049.0 cell/mm, 41% decrease) in group CB and 1403.0
cell/mm (972.5-2010.7 cell/mm, 46% decrease) in group SST (P = .70). Rebubbling
was required in 5 CB (45.5%) and 15 SST (68.2%) subjects (P = .39).Fuchs'
dystrophy patients have good anatomic and functional DMEK results. Similar
outcomes and complication rates occurred with eye bank and surgeon prepared donor
tissue.
PMID- 28489793
TI - A selective screening program for the early detection of mucopolysaccharidosis:
Results of the FIND project - a 2-year follow-up study.
AB - The mucopolysaccharidoses (MPSs) are underdiagnosed but they are evaluated in few
newborn screening programs, probably due to the many challenges remaining, such
as the identification of late-onset phenotypes. Systematic screening at the onset
of clinical symptoms could help to early identify patients who may benefit from
specific treatments. The aim of this prospective study was to assess a novel
selective screening program, the FIND project, targeting patients aged 0 to 16
years with clinical manifestations of MPS. The project was designed to increase
awareness of these diseases among pediatricians and allow early diagnosis.From
July 2014 to June 2016, glycosaminoglycan (GAG) levels normalized to creatinine
levels were determined in urine-impregnated analytical paper submitted by
pediatricians who had patients with clinical signs and/or symptoms compatible
with MPS. When high GAG concentrations were detected, a new liquid urine sample
was requested to confirm and identify the GAG present. When a specific form of
MPS was suspected, enzyme activity was analyzed using blood-impregnated paper to
determine MPS type (I, IIIB, IIIC, IVA, IVB, VI, or VII). Age-specific reference
values for GAG were previously established using 145 urine samples from healthy
children.GAG levels were normal in 147 (81.7%) of the 180 initial samples
received. A liquid sample was requested for the other 33 cases (18.3%); GAG
levels were normal in 13 of these and slightly elevated in 12, although the
electrophoresis study showed no evidence of MPS. Elevated levels with
corresponding low enzymatic activity were confirmed in 8 cases. The mean time
from onset of clinical symptoms to detection of MPS was 22 months, and just 2
cases were detected at the beginning of the project were detected with 35 and 71
months of evolution of clinical symptoms. Our screening strategy for MPS had a
sensitivity of 100%, a specificity of 85%, and a positive predictive value of
24%.The FIND project is a useful and cost-effective screening method for
increasing awareness of MPS among pediatricians and enabling the detection of MPS
at onset of clinical symptoms.
PMID- 28489795
TI - Effects of rational emotive behavior coaching on occupational stress and work
ability among electronics workshop instructors in Nigeria.
AB - BACKGROUND/OBJECTIVE: This study examined the effectiveness of rational emotive
behavior coaching (REBC) on occupational stress and work ability in a sample of
electronics workshop instructors in Nigeria. METHODS: A pretest-posttest control
group design was used. The participants were 108 electronics workshop instructors
in technical colleges in the south-east of Nigeria who met the study inclusion
criteria. Data were collected using 3 questionnaires and analyzed using a
repeated measure analysis of variance and Mann-Whitney U test. RESULTS: REBC led
to a significant reduction in occupational stress experienced by the electronics
workshop instructors in the REBC group compared to their counterparts in the
waitlist control group. Furthermore, the scores for occupation-related irrational
beliefs of the instructors in the REBC group were significantly lower than those
in the waitlist control group at the end of the coaching intervention. The work
ability of the REBC group was significantly better than that of the waitlist
control group. Finally, the effects in the REBC group were significantly
sustained at 3-month follow-up. CONCLUSION: REBC is a time-efficient and solution
focused therapeutic modality for assisting occupationally stressed employees in a
Nigerian setting. REBC can be used for improving and maintaining work ability of
workers. The researchers hope that occupational health professionals and health
counselors would extend this approach to tackle psychological issues limiting
employees' effectiveness and performance in the Nigerian work environment and in
other countries.
PMID- 28489794
TI - Meta-analysis of studies using metformin as a reducer for liver cancer risk in
diabetic patients.
AB - Metformin has garnered more interest as a chemo-preventive agent given the
increased liver cancer risk in diabetic patients. This work was undertaken to
better understand the effect of metformin use on liver cancer risk in diabetic
patients.A comprehensive literature search was performed in PubMed, Embase,
BIOSIS Previews, Web of Science, and Cochrane Library through July 30, 2016. Meta
analyses were performed using Stata version 12.0, with odds ratio (ORs) and 95%
confidence intervals (CIs) as effect measures.Twenty-three studies were included.
Meta-analysis of 19 studies involving 550,882 diabetic subjects suggested that
metformin use reduced the ratio of liver cancer by 48% (OR = 0.52; 95% CI, 0.40
0.68) compared with nonusers. The protective effect was validated in all the
exploratory subgroup analyses, except that pooled result of post hoc analyses of
2 randomized controlled trials found no significant difference between subjects
with metformin and those without, with OR being 0.84 (95% CI, 0.10-6.83). After
adjusting for hepatitis B/C virus infection, cirrhosis, obesity, behavioral
factors, and time-related bias, the association was stable, pooled OR ranged from
0.42 to 0.75.A protective effect for liver cancer was found in diabetic metformin
users. However, more randomized clinical evidence is still needed to verify the
results.
PMID- 28489796
TI - Leptomeningeal metastasis of poorly differentiated uterine cervical adenosquamous
carcinoma following reirradiation to metastatic vertebrae: A case report.
AB - RATIONALE: Leptomeningeal metastasis from cervical adenosquamous carcinoma is
extremely rare especially after radiotherapy for vertebral metastasis. PATIENT
CONCERNS: A 52-year-old woman with International Federation of Gynecology and
Obstetrics (FIGO) stage IIB adenosquamous carcinoma of cervix presented with
bilateral lower limbs weakening after 2 courses radiotherapy to thoracic
vertebral metastases. DIAGNOSES: Initial spine magnetic resonance imaging (MRI)
showed no obvious nerve compression, and radiation myelopathy was suspected by
the clinician. Progressive multifocal neurological signs developed one month
after completion of spine re-irradiation. She was diagnosed with leptomeningeal
metastasis by MRI and cerebrospinal fluid (CSF) study. INTERVENTIONS: She
received whole brain irradiation with a dose of 30 Gy in 10 fractions. Systemic
chemotherapy with cisplatin (50 mg/m) and topotecan (0.75 mg/m) was administered
sequentially. OUTCOMES: She died with progressive disease two months after the
diagnosis of leptomeningeal metastases. LESSONS: Poorly differentiated advanced
stage cervical adenosquamous carcinoma is an aggressive neoplasm with a worse
outcome. Leptomeningeal metastasis should be included in the differential
diagnosis for patients with multifocal craniospinal neurological signs. A
combination of detailed neurological examinations, MRI and CSF study allowed us
to establish a correct diagnosis of leptomeningeal metastasis and initiate
treatment in a timely manner.
PMID- 28489797
TI - A previously published propofol-remifentanil response surface model does not
predict patient response well in video-assisted thoracic surgery.
AB - Modern anesthesia usually employs a hypnotic and an analgesic to produce
synergistic sedation and analgesia. Two remifentanil-propofol interaction
response surface models were used to predict sedation using Observer's Assessment
of Alertness/Sedation (OAA/S) scores; one predicts an OAA/S <2 and the other <4.
We hypothesized that both models would predict regained responsiveness (RR) after
video-assisted thoracic surgery (VATS) to reduce total anesthesia time and make
early extubation clinically relevant. We included 30 patients undergoing VATS
received total intravenous anesthesia (TIVA) combined with thoracic epidural
anesthesia (TEA). Pharmacokinetic profiles were calculated using Tivatrainer.
Model predictions were compared with observations to evaluate the accuracy and
precision of emergence model predictions. The mean (standard deviation)
differences between when a patient responded to their name and the time when the
model predicted a 50% probability of patient response were 30.80 +/- 17.77 and
13.71 +/- 11.35 minutes for the OAA/S <2 model and <4 model, respectively. Both
models had a limited ability to predict patient response in our patients. Both
models identified target concentration pairs predicting time of RR in volunteers
and some elective surgeries, but another model of epidural and intravenous
anesthetic combinations may be needed to predict time of RR after VATS under TIVA
with TEA.
PMID- 28489798
TI - Efficacy of functional microarray of microneedles combined with topical
tranexamic acid for melasma: A randomized, self-controlled, split-face study.
AB - To evaluate the efficacy of a functional microarray of microneedles (MNs) plus
topical tranexamic acid (TA) for melasma in middle-aged women in China.Thirty
female subjects with melasma were enrolled in this study. The left or right side
of the face was chosen randomly to be pretreated with a functional microarray of
MNs, followed by topical 0.5% TA solution once per week for 12 weeks. The other
half-face was the control, treated with a sham device plus topical 0.5% TA
solution. At baseline and at weeks 4, 8, and 12 of treatment, clinical
(photographic) evaluations and parameters determined by Visia were recorded. At
baseline and week 12, patient satisfaction scores and the biophysical parameters
measured by Mexameter were also recorded. Side effects were evaluated at baseline
and at the end of the 12 weeks.In total, 28 women (93.3%) completed the study.
The brown spots' scores measured by Visia were significantly lower on the
combined therapy side than on the control side at 12 weeks after starting
treatment; there was no significant difference between sides at 4 or 8 weeks.
After 12 weeks, melanin index (MI) decreased significantly in both 2 groups, and
the MI was significantly less on the combined side at week 12. Transepidermal
water loss, roughness, skin hydration, skin elasticity, and erythema index showed
no significant differences between 2 sides at baseline, 4, 8, and 12 weeks after
treatment. Physicians' evaluations of photographs showed better results at week
12 with combined therapy: >25% improvement was observed in the MNs plus TA side
in 25 patients, and in the TA side in only 10 patients. Subjective satisfaction
scores on both sides increased significantly. The participants were more
satisfied with the results of the combined therapy side than the control side. No
obvious adverse reactions were observed throughout the study.Combined therapy
with a functional microarray of MNs and topical TA solution is a promising
treatment for melasma.
PMID- 28489799
TI - Comparison of clinical outcomes in peripartum cardiomyopathy and age-matched
dilated cardiomyopathy: A 15-year nationwide population-based study in Asia.
AB - Peripartum cardiomyopathy (PPCM), often classified as a form of dilated
cardiomyopathy (DCM), is the myocardial dysfunction that occurs in late pregnancy
and through the first few postpartum months.The aim of this study is to
investigate the differences in the clinical outcomes of PPCM and DCM.Electronic
medical records from 1997 to 2011 were retrieved from the Taiwan National Health
Insurance Research Database. Patients with PPCM were compared with age- and
clinical characteristics-matched patients with DCM. Primary outcomes were 1- and
3-year heart failure (HF) readmission, cardiac death, all-cause mortality, and
major adverse cardiovascular events. Secondary outcomes were myocardial
infarction, new onset of dialysis, heart transplant, and cerebrovascular
accident. Follow-up period was divided into "within the first year" and "after
the first year."A total of 527,979 patients (253,166 females) were hospitalized
with a principal diagnosis of HF during 1997 to 2011 period. After excluding
patients aged <18 and >50 years, patients with other forms of HF, and those with
a history of cerebrovascular accidents or coronary artery disease, 797 patients
with PPCM and 1267 patients with DCM were evaluated. Propensity score matching
yielded 391 patients in each group. Patients with DCM had a significantly worse
prognosis compared to those with PPCM for all primary and secondary outcomes at
the 1- and 3-year follow-ups. After 1 year, the HF readmission rate did not
significantly differ between the 2 diseases, suggesting that HF medications
should be aggressively instituted in patients with PPCM.This is the first study
to directly compare the clinical outcomes between age-matched patients with PPCM
and DCM. Patients with PPCM had a significantly better prognosis across all
cardiovascular endpoints compared to patients with DCM.
PMID- 28489800
TI - Characteristics and outcome of spontaneous bacterial meningitis in patients with
cancer compared to patients without cancer.
AB - In cancer patients, who are frequently immunocompromised, bacterial meningitis
(BM) can be a severe complication, with a different presentation, etiology, and
course, compared to patients without cancer. Our objective is to compare the
characteristics and outcomes of BM in patients with and without cancer. A single
center, prospective observational cohort study, conducted between 1982 and 2012,
in a tertiary university hospital in Barcelona (Spain). The main outcome measure
is in-hospital mortality. We evaluated 659 episodes of BM; 97 (15%) had active
cancer. Patients with malignancies were older (median 63 (interquartile range
[IQR] 24) vs 52 [IQR 42] years, P < .001) and more often had a Charlson
comorbidity score of >=3 (51% vs 11%, P < .001). The classic meningitis triad
(35% vs 50%, P = .05), fever (91% vs 96%, P = .03), neck stiffness (58% vs 78%, P
< .001), headache (63% vs 77%) P = .003), and rash (7% vs 30%, P < .001) were
less frequent. There was a longer interval between admission and antibiotic
therapy (median 5 [IQR 14] vs 3 [IQR 6] hours, P < .001). Listeria meningitis was
the commonest cause of BM (29%) and was more frequent in cancer than noncancer
(8%, P < .001) patients, whereas meningococcal meningitis was much less frequent
(4% vs 36%, P < .001). Overall mortality was higher in patients with cancer (31%
vs 16%, P < .001), although cancer was not associated with an unfavorable outcome
in the multivariate analysis (odds ratio 1.825, P = .07). Patients with
meningitis and cancer are older and have more subtle clinical manifestations than
patients without cancer. Listeria monocytogenes is the predominant pathogen and
mortality is higher in cancer patients.
PMID- 28489801
TI - A CARE-compliant case report: Lung transplantation for a Chinese young man with
idiopathic pleuroparenchymal fibroelastosis.
AB - RATIONAL: Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial lung
disease that is characterized radiologically by apical pleural thickening and
histologically by elastic fibrosis of the visceral pleura. Although PPFE cases
have been reported occasionally since this disease was initially described, most
such cases have involved secondary PPFE. Idiopathic PPFE (iPPFE) cases have been
less thoroughly studied. There are no effective medications for patients with
iPPFE. PATIENT CONCERNS: A 34-year-old man with no asbestos or cigarette exposure
was admitted to our ward due to worsening cough and exertional dyspnea for 10
years. He had a "flattened thoracic cage" and bibasilar inspiratory crackles
without finger clubbing. A series of chest computed tomography scans during the
preceding 10 years revealed the presence of gradual, exaggerated, upper lung
predominant, diffuse pleural thickening and dense subpleural opacification with
traction bronchiectasis. DIAGNOSIS: He was performed with video-assisted thoracic
surgical (VATS) lung biopsy. The pulmonary histopathologic examination showed
thickened visceral pleura and prominent subpleural fibroelastosis, confirming the
diagnosis of iPPFE. INTERVENTION: After the failure of treatment with prednisone
plus cyclophosphamide and sequential pirfenidone administration, he was arranged
with bilateral lung transplantation two years later. OUTCOMES: The patient did
not require supplemental oxygenation anymore after he recovered from lung
transplantation. LESSONS: Bilateral lung transplantation might be tried for the
end-stage iPPFE cases.
PMID- 28489802
TI - Combined effect of serum gamma-glutamyltransferase and uric acid on incidence of
diabetes mellitus: A longitudinal study.
AB - Gamma-glutamyltransferase (GGT) and uric acid (UA) are novel diabetes risk
factors. However, little is known about the combined effects of GGT and UA on the
development of diabetes. Here, we assessed the combined effects of GGT and UA on
the development of diabetes in a Korean population.We evaluated 1983 women and
2687 men without diabetes. From the baseline health screening to the follow-up
examination, the development of diabetes, based on changes in GGT and UA quartile
levels, was analyzed. Furthermore, the quartile of GGT and quartile of UA were
analyzed together to determine any synergistic effect from the 4th quartile of
GGT and UA on the development of diabetes.In women, the development of diabetes
gradually increased with an increase in the circulating levels of GGT and UA. For
the highest quartile of GGT and UA, hazard ratios of diabetes compared with the
lowest quartile were 3.88 (95% confidence interval [CI]: 1.12-13.43, P = .032)
and 7.58 (95% CI: 2.17-26.42, P = .002) after adjusting for confounders,
respectively. Hazard ratios of diabetes after combining both 4th quartiles of GGT
and UA were 5.29 (95% CI: 1.87-15.18, P = .002), as compared with the first and
second quartiles. In men, however, the development of diabetes was not
significantly different among the quartiles of UA.GGT and UA levels can synergize
in predicting the development of diabetes in Korean women.
PMID- 28489803
TI - Reproducibility analysis on shear wave elastography (SWE)-based quantitative
assessment for skin elasticity.
AB - Shear Wave Elastography (SWE) is an objective and non-invasive method widely used
to quantify the tissue solidity. However, there are concerns about the accuracy
of the skin SWE results due to the low signal-to-noise ratio (SNR) caused by
subcutaneous fat, muscle and bone. This article analyzed the reproducibility of
the result for skin SWE and therefore evaluated the availability of SME for skin
elasticity involved diseases. Thirty volunteers (mean age: 37 +/- 12 years) were
selected. SWE were taken on the skin of abdomen and the middle tibia in order to
assess the impact of fat, muscle and bone on SWE results. Skin in the area of
anterior and lateral tibia marked with seven parallel lines, and each line
indicated an identical thickness of the subcutaneous fat from 1-7 mm. Intra-class
correlation coefficients (ICC) were used to evaluate the intra-observer and inter
observer reproducibility. The solidity of abdominal skin showed soft and small
individual differences (12.4 +/- 2.7 kPa), whereas high shear moduli (25-48 kPa)
were observed in the skin above tibia and tibialis anterior muscle. When the
subcutaneous fat was thicker than 3 mm (>=3), we obtained excellent intra
observer reproducibility (ICC range 0.78-0.98) and inter-observer reproducibility
(ICC range 0.75-0.98). The thickness of subcutaneous fat could affect the
reproducibility of skin SWE. The further study on skin SWE standardization should
be taken.
PMID- 28489804
TI - Comparison of learning performance of 2 intubating laryngeal mask airways in
novice: A randomized crossover manikin study.
AB - BACKGROUND: Intubating laryngeal mask airways (LMAs) such as i-gel and Aura-i
could serve as rescue devices in resuscitation and further ensure the airway by
facilitating trachea intubation without ventilation interruption. But data
regarding intubating LMAs in novice are limited and skill degeneration without
regular training has not been evaluated. So we designed this prospective
randomized crossover manikin study to compare the learning performance of 2
intubating LMAs (i-gel and Aura-i). METHODS: In total, 46 novice doctors
participated in this study. After standardized training and finishing 3
consecutive successful intubations with both LMAs on manikin, each participant
applied intubation with both LMAs in random order for initial evaluation. To
evaluate skill retention, participants were reassessed 90 days later on the same
manikin without retraining between times. Primary outcome was time to successful
ventilation (TTV). RESULTS: The TTV for i-gel was significantly shorter than Aura
i (initial evaluation 11.8 +/- 2.9 seconds vs 22.4 +/- 5.2 seconds, 90-days
reevaluation 14.9 +/- 3.6 seconds vs 28.9 +/- 10.0 seconds, initial evaluation, P
= .001; second evaluation, P < .001); during re-evaluation, TTV taken for i-gel
and Aura-i were both significantly longer (initial evaluation, P = .001; second
evaluation, P < .001) and ease score of insertion both increased profoundly (i
gel P = .025; Aura-i P < .001). In both assessments, participants preferred i-gel
as easier alternative (initial evaluation, P = .001; second evaluation, P <
.001). There was no difference in successful intubation rate, first attempt
success rate, bronchoscopy assessment, and insertion score for 2 LMAs.
CONCLUSION: Compared with Aura-i, i-gel showed a faster and easier intubation by
novice doctors in this manikin study; the skill retention of intubation
performance after 3 months was acceptable for both intubating LMAs, but TTV
prolonged significantly.
PMID- 28489805
TI - First experience of nDSAEK with heads-up surgery: A case report.
AB - PURPOSE: To report a case of non-Descemet Stripping Automated Endothelial
Keratoplasty (nDSAEK) using heads-up surgery. CASE/INTERVENTION: The case was a
72-years-old man who had history of left eye blunt trauma since childhood. One
year ago, the patient was diagnosed to have left posttraumatic bullous
keratopathy. The patient underwent lt nDSAEK by using the heads-up three
dimensional (3D) system last July. The surgery was performed with a Rescan 700
surgical microscope (Carl Zeiss), which is integrated with intraoperative optical
coherence tomography (iOCT) system. During surgery, the surgeon and audience wore
3D passive polarized glasses. A 42 inch high-definition (HD) display and 2 HD
cameras (Sony) were used. With this 3D system, the nDSAEK procedure before the
graft insertion into the anterior chamber was easy especially with available high
magnification. Also, using iOCT of the system enables the surgeon to detect any
residual fluid at the donor graft-recipient interface and locate its place to be
drained. The only disadvantage of the system was the difficulty in the detection
of nDSAEK graft depth in the anterior chamber, which required frequent focus
change during the surgery. Although the surgeon frequently adjusted the focus for
clear stereoscopic view of the graft, he did not feel any eye strain or
discomfort. All other steps of the procedure were performed without any problem
and postoperative course of the patient was good. CONCLUSION: Using heads-up
surgery for performing anterior segment surgeries is encouraging and promising.
PMID- 28489806
TI - The relationship between corneal biomechanics and anterior segment parameters in
the early stage of orthokeratology: A pilot study.
AB - To investigate the relationship between corneal biomechanics and anterior segment
parameters in the early stage of overnight orthokeratology.Twenty-three eyes from
23 subjects were involved in the study. Corneal biomechanics, including corneal
hysteresis (CH) and corneal resistance factor (CRF), and parameters of the
anterior segment, including corneal curvature, central corneal thickness (CCT),
and corneal sublayers' thickness, were measured at baseline and day 1 and 7 after
wearing orthokeratology lens. One-way analysis of variance with repeated measures
was used to compare the longitudinal changes and partial least squares linear
regression was used to explore the relationship between corneal biomechanics and
anterior segment parameters.At baseline, CH and CRF were positively correlated
with CCT (r = 0.244, P = .008 for CH; r = 0.249, P < .001 for CRF), central
stroma thickness (CST) (r = 0.241, P = .008 for CH; r = 0.244, P = .002 for CRF)
and central Bowman layer thickness (CBT) (r = 0.138, P = .039 for CH; r = 0.171,
P = .006 for CRF). Both CH and CRF significantly decreased from day 1 after
orthokeratology. The corneal curvature and the epithelium thickness also
significantly decreased, while the stromal layer thickened significantly from day
1 after orthokeratology. There was no correlation between the changes of corneal
biomechanics and anterior segment parameters at day 1 and 7 after
orthokeratology.While corneal biomechanics were positively correlated with CCT,
CST, and CBT, the changes of CH and CRF were not correlated with the changes of
corneal curvature, CCT, and corneal sublayers' thickness in the early stage of
orthokeratology in our study.
PMID- 28489807
TI - Comparative study of short- and long-term outcomes of laparoscopic-assisted
versus open rectal cancer resection during and after the learning curve period.
AB - Laparoscopic-assisted rectal resection (LAR) has been widely used to treat rectal
cancer. However, it has a steep learning curve. In this study, we aimed to
investigate the effects of the learning curve on the outcomes of LAR. All
consecutive patients with rectal cancer undergoing LAR or open resection (OR)
between 2010 and 2015 were included in this retrospective analysis. The learning
curve was determined, and patients were divided into 2 phases: the learning curve
and the expert period. The short-term perioperative data in the 2 phases and the
long-term survival in the learning phase were compared between the LAR and OR
groups. A total of 491 patients were included in this study. Inflection of the
learning curve based on the operation time of LAR was at the 40th case. A total
of 233 patients underwent surgery (112 LAR and 121 OR) during the learning
period. In this period, LAR had a longer operation time, less blood loss, and a
higher total cost (all P < .05). The 3-year overall survival rates between the
LAR and OR groups were similar (69.74% vs 75%; P = .32). A total of 258 patients
underwent surgery (169 LAR and 89 OR) during the expert period. Significant
differences in total cost, estimated blood loss, postoperative hospital stay, and
recovery of bladder and bowel functions were identified in this period (all P <
.05). LAR during the learning period has fewer benefits in terms of postoperative
recovery than OR. However, the long-term outcomes are equivalent.
PMID- 28489808
TI - Mental health status after living donor hepatectomy.
AB - Donor safety and preservation of donor health after living liver donation are of
paramount importance. In addition, the preoperative mental state of a donor is an
important factor in determining the psychological impact of donor hepatectomy.
Thus, we aimed to explore the mental health status of living liver donors after
hepatectomy. We enrolled 60 donors who were scheduled to undergo living donor
hepatectomy during the period January 2014 to March 2015 at a single medical
center. Mental health status was measured before and 3 months after surgery using
3 self-report questionnaires, namely the Center for Epidemiologic Studies
Depression Scale (CES-D) to assess depressive symptoms, the World Health
Organization Quality of Life (WHOQOL-BREF) questionnaire to measure quality of
life, and the Chinese Health Questionnaire (CHQ) to screen for minor psychiatric
disorders. A comparison of the pre- and postdonation CES-D scores revealed a
significant reduction in depressive symptoms after surgery (P = .031). There were
significant improvements in the physical health domain (P = .031), the
psychological health domain (P = .005), the social relationships domain (P =
.005), and the environmental health domain (P = .010) of the WHOQOL-BREF. There
were no significant changes in CHQ scores after donor hepatectomy (P = .136). All
donors reported that they would donate again if required. Approximately one-third
(33.3%) of donors experienced more pain than they had anticipated in the
immediate postoperative period, and 20.0% of donors had complications after donor
hepatectomy. Donor mental health status tended to improve as donors regained
physical function during the 1st 3 months of recovery. Long-term monitoring of
living donors' mental health is needed to minimize the adverse psychological
outcomes of living liver donation.
PMID- 28489809
TI - Cannabis-induced bullous lung disease leading to pneumothorax: Case report and
literature review.
AB - RATIONALE: Marijuana use has been increasing in the United States among college
students and young adults. Marijuana use has been associated with bullous lung
disease which can lead to pneumothorax. There are other recreational drugs like
methylphenidate, cocaine and heroin which have been associated with pneumothorax.
PATIENT CONCERNS: We present a case of a 30-year-old man with spontaneous
pneumothorax associated with marijuana use. The patient had no medical conditions
and presented to the emergency room with chest pain. The physical examination
revealed decreased breath sound on the right side of the chest. DIAGNOSES: Bed
side ultrasound of chest showed stratosphere sign, absent lung sliding;
consistent with right-sided pneumothorax. INTERVENTIONS AND OUTCOMES: The patient
underwent placement of a chest tube. Computed tomography chest scans performed on
day two also showed bullous lung disease in the right lung. Serial x-rays of the
chest showed re-expansion of the lung. LESSONS: Despite the beneficial effects of
Marijuana there are deleterious effects which are emphasized here. This case
highlights the need for further studies to establish the relationship between
marijuana use and lung diseases in the absence of nicotine use.
PMID- 28489810
TI - A case report of hereditary neuropathy with liability to pressure palsies
accompanied by type 2 diabetes mellitus and psoriasis.
AB - RATIONALE: Hereditary neuropathy with liability to pressure palsy (HNPP) is an
episodic, multifocal neuropathy, with a typical clinical presentation of
recurrent transient pressure palsies, which is induced by a PMP22 deletion.
Another neuropathy caused by a PMP22 duplication is Charcot-Marie-Tooth disease
type 1A (CMT1A). PMP22 is a gene coding a protein called peripheral myelin
protein 22 (PMP22), which plays an essential role in the formation and
maintenance of compact myelin. Coexistence of type 2 diabetes mellitus (T2DM) and
CMT1A has been reported in many work, however HNPP patients with T2DM are rare,
and comorbidity of HNPP and psoriasis has not been reported previously.
Electrophysiological features of HNPP has been found progressing with aging.
Patient concerns: Here we present a 20-year-old man who exhibited lower extremity
weakness and foot drop as the initial manifestation. DIAGNOSES: HNPP was
diagnosed on the basis of clinical features, positive sural nerve biopsy
findings, and genetic testing results. Moreover, physical examination,
blood/urine glucose test, and diabetes-related autoantibodies investigations
demonstrated that he had psoriasis and T2DM. The electrophysiological
manifestations revealed profound demyelinating injuries and axonal injuries in
distal peripheral nerves and facial nerves, which were more severe than general
HNPP cases. INTERVENTIONS: The young patient was treated with continuous
subcutaneous insulin infusion and blood glucose monitoring, and then transferred
to oral acarbose therapy. The psoriatic lesions were treated with calcipotriol
ointment. OUTCOMES: In the follow-up, the right leg weakness was alleviated, and
his gait was improved. LESSONS: The findings indicate that diabetes mellitus may
have an impact on the severity of HNPP. Physicians should consider that worsening
of symptoms might result from newly diagnosed diabetes mellitus while treating
patients with HNPP.
PMID- 28489811
TI - Intravascular large b-cell lymphoma diagnosed via transjugular liver biopsy in a
patient with liver dysfunction and thrombocytopenia: A Case Report.
AB - RATIONALE: Intravascular large B-cell lymphoma (IVLBCL) is an extremely rare
subtype of large B-cell lymphoma characterized by the presence of lymphoma cells
within the lumen of small blood vessels. IVLBCL presents with nonspecific
symptoms such as fever, weight loss, and bleeding. Because of its rarity and
unremarkable clinical presentation, a timely diagnosis is very challenging.
PATIENT CONCERNS: A 71-year-old Korean man complained of fever, but apart from
pretibial pitting edema and mild thrombocytopenia, the physical examination and
laboratory test findings were unremarkable. DIAGNOSES: A bone marrow biopsy was
also nonspecific. The fever persisted and his thrombocytopenia became more
pronounced, prompting further laboratory tests that indicated infiltrative liver
disease. INTERVENTIONS: Because of coagulopathy, a liver biopsy was performed
using a transjugular instead of apercutaneous approach. OUTCOMES: The procedure
was performed without complications, and the pathologic examination findings were
consistent with IVLBCL. Unfortunately, the patient died because of disease
progression before treatment could be administered. LESSONS: Given that an early
diagnosis can affect the prognosis of IVLBCL, quickly and safely obtaining a
biopsy specimen is very important. The case presented here shows that a liver
biopsy obtained via a transjugular approach is safe and could be preferentially
considered when there is a high risk for bleeding complications.
PMID- 28489812
TI - Are public health physicians still needed in medically underserved rural areas in
Korea?
AB - Public health physicians (PHPs) are certified physicians who are serving in a
public health center or subcenter in a rural village, instead of serving in the
military. However, the PHP program has recently become the subject of a profound
debate, over 30 years after its adoption. In this study, we attempted to
ascertain physicians' perspectives on the PHP program, including: whether the PHP
policy should continue; if they agree on changing the role of PHPs in healthcare;
what would be the desired role of PHPs; and what resources would be required and
what possible barriers would be anticipated under the changes. We selected 88
PHPs as our study sample using quota sampling. Over 60% of respondents were in
support of continuing the PHP program. They believed some remote islands and
mountainous areas are still in need of public healthcare doctors. However, some
of them believed that the role of PHPs should be changed to take on community
health promotion, because the problem of medically underserved rural areas has
almost been resolved. However, people living in rural areas are ageing and
suffering from a lack of education and health information. In particular, in
order to successfully transition into new roles, PHPs must be provided with
continuing education and professional development programs covering their new
responsibilities. It is imperative to refurbish the PHP program to meet current
needs and continue its central role in public healthcare.
PMID- 28489813
TI - Implementing a novel model for hospice and palliative care in the emergency
department: An experience from a tertiary medical center in Taiwan.
AB - Hospice and palliative care has been recognized as an essential part of emergency
medicine; however, there is no consensus on the optimal model for the delivery of
hospice and palliative care in the emergency department (ED). Therefore, we
conducted a novel implementation in a tertiary medical center in Taiwan. In the
preintervention period, we recruited a specialist for hospice and palliative
medicine in the ED to lead our intervention. In the early stage of the
intervention, starting on July 1, 2014, we encouraged and funded ED physicians
and nurses to receive training for hospice and palliative medicine and residents
of emergency medicine to rotate to the hospice ward. In the late stage of the
intervention, we initiated educational programs in the ED, an interdisciplinary
meeting with the hospice team every month, sharing information and experience via
a cell phone communication app, and setting aside an emergency hospice room for
end-of-life patients. We compared the outcomes among pre-, during, and
postintervention periods. Compared with 4 in the preintervention period, the
cases of do not resuscitate (DNR) per month increased significantly to 30.1 in
the early stage of intervention, 23.9 in late stage of intervention, and 34.6 in
the postintervention period (all P < .001 compared with the preintervention
period). Compared with 10.8% in the preintervention period, the ratio of DNR
orders signed in the ED/total DNR orders signed in the study hospital was
increased to 17.1% in early stage of intervention, 12.5% in late stage of
intervention, and 22.8% in postintervention. Compared with zero in
preintervention and early intervention, the cases of consultation with the
hospice team increased significantly to 19 cases per month in the late stage of
intervention and postintervention. The ability of nurses in hospice and
palliative care, including knowledge and the timing and method of consultation
with the hospice team, was also significantly improved. We successfully
implemented a novel model of hospice and palliative care in the ED via a
champion, education, and close collaboration with the hospice team, which could
be an important reference for other EDs and intensive care unit in the future.
PMID- 28489814
TI - Diagnostic Values of Serum Levels of Homocysteine and Uric Acid for Predicting
Vascular Mild Cognitive Impairment in Patients with Cerebral Small Vessel
Disease.
AB - BACKGROUND This study aimed to investigate the diagnostic values of serum levels
of Hcy and UA for predicting vascular mild cognitive impairment (VMCI) in
patients with cerebral small vessel disease (SVD). MATERIAL AND METHODS We
selected 172 cerebral SVD patients and divided them into a VMCI group and a non
VMCI group. Eighty-six healthy individuals without nervous system diseases were
selected as the control group. Enzymatic cycling method was performed to detect
serum Hcy and UA levels. Serum levels of folic acid (FOA) and vitamin B12
(VitB12) were detected by chemiluminescence immunoassay. Montreal cognitive
assessment (MoCA) was applied to evaluate the cognitive function. The ROC curve
was used to evaluate the diagnostic values of serum Hcy and UA levels for
predicting VMCI. Logistic regression analysis was used to determine the possible
risk factors. RESULTS Compared with the non-VMCI and control groups, serum FOA
and VitB12 levels were lower and serum Hcy and UA levels were higher in the VMCI
group. AUC values of serum Hcy and UA levels were 0.703 and 0.829, respectively.
Serum Hcy and UA levels were negatively correlated with serum FOA and VitB12
levels, total MoCA score, and subscores on visuospatial ability and executive
function, on language ability and on delayed recall, and they were positively
correlated with serum cholesterol (CH) level. Serum Hcy and UA levels were
indicated as risk factors for VMCI in cerebral SVD patients. CONCLUSIONS These
results suggest that serum Hcy and UA levels may serve as predictive factors for
VMCI in cerebral SVD patients.
PMID- 28489815
TI - Common genetic variation drives molecular heterogeneity in human iPSCs.
AB - Technology utilizing human induced pluripotent stem cells (iPS cells) has
enormous potential to provide improved cellular models of human disease. However,
variable genetic and phenotypic characterization of many existing iPS cell lines
limits their potential use for research and therapy. Here we describe the
systematic generation, genotyping and phenotyping of 711 iPS cell lines derived
from 301 healthy individuals by the Human Induced Pluripotent Stem Cells
Initiative. Our study outlines the major sources of genetic and phenotypic
variation in iPS cells and establishes their suitability as models of complex
human traits and cancer. Through genome-wide profiling we find that 5-46% of the
variation in different iPS cell phenotypes, including differentiation capacity
and cellular morphology, arises from differences between individuals.
Additionally, we assess the phenotypic consequences of genomic copy-number
alterations that are repeatedly observed in iPS cells. In addition, we present a
comprehensive map of common regulatory variants affecting the transcriptome of
human pluripotent cells.
PMID- 28489816
TI - Endothelial TLR4 and the microbiome drive cerebral cavernous malformations.
AB - Cerebral cavernous malformations (CCMs) are a cause of stroke and seizure for
which no effective medical therapies yet exist. CCMs arise from the loss of an
adaptor complex that negatively regulates MEKK3-KLF2/4 signalling in brain
endothelial cells, but upstream activators of this disease pathway have yet to be
identified. Here we identify endothelial Toll-like receptor 4 (TLR4) and the gut
microbiome as critical stimulants of CCM formation. Activation of TLR4 by Gram
negative bacteria or lipopolysaccharide accelerates CCM formation, and genetic or
pharmacologic blockade of TLR4 signalling prevents CCM formation in mice.
Polymorphisms that increase expression of the TLR4 gene or the gene encoding its
co-receptor CD14 are associated with higher CCM lesion burden in humans. Germ
free mice are protected from CCM formation, and a single course of antibiotics
permanently alters CCM susceptibility in mice. These studies identify unexpected
roles for the microbiome and innate immune signalling in the pathogenesis of a
cerebrovascular disease, as well as strategies for its treatment.
PMID- 28489817
TI - Selectivity determinants of GPCR-G-protein binding.
AB - The selective coupling of G-protein-coupled receptors (GPCRs) to specific G
proteins is critical to trigger the appropriate physiological response. However,
the determinants of selective binding have remained elusive. Here we reveal the
existence of a selectivity barcode (that is, patterns of amino acids) on each of
the 16 human G proteins that is recognized by distinct regions on the
approximately 800 human receptors. Although universally conserved positions in
the barcode allow the receptors to bind and activate G proteins in a similar
manner, different receptors recognize the unique positions of the G-protein
barcode through distinct residues, like multiple keys (receptors) opening the
same lock (G protein) using non-identical cuts. Considering the evolutionary
history of GPCRs allows the identification of these selectivity-determining
residues. These findings lay the foundation for understanding the molecular basis
of coupling selectivity within individual receptors and G proteins.
PMID- 28489818
TI - A Wnt-producing niche drives proliferative potential and progression in lung
adenocarcinoma.
AB - The heterogeneity of cellular states in cancer has been linked to drug
resistance, cancer progression and the presence of cancer cells with properties
of normal tissue stem cells. Secreted Wnt signals maintain stem cells in various
epithelial tissues, including in lung development and regeneration. Here we show
that mouse and human lung adenocarcinomas display hierarchical features with two
distinct subpopulations, one with high Wnt signalling activity and another
forming a niche that provides the Wnt ligand. The Wnt responder cells showed
increased tumour propagation ability, suggesting that these cells have features
of normal tissue stem cells. Genetic perturbation of Wnt production or signalling
suppressed tumour progression. Small-molecule inhibitors targeting essential
posttranslational modification of Wnt reduced tumour growth and markedly
decreased the proliferative potential of lung cancer cells, leading to improved
survival of tumour-bearing mice. These results indicate that strategies for
disrupting pathways that maintain stem-like and niche cell phenotypes can
translate into effective anti-cancer therapies.
PMID- 28489819
TI - Predictive compound accumulation rules yield a broad-spectrum antibiotic.
AB - Most small molecules are unable to rapidly traverse the outer membrane of Gram
negative bacteria and accumulate inside these cells, making the discovery of much
needed drugs against these pathogens challenging. Current understanding of the
physicochemical properties that dictate small-molecule accumulation in Gram
negative bacteria is largely based on retrospective analyses of antibacterial
agents, which suggest that polarity and molecular weight are key factors. Here we
assess the ability of over 180 diverse compounds to accumulate in Escherichia
coli. Computational analysis of the results reveals major differences from the
retrospective studies, namely that the small molecules that are most likely to
accumulate contain an amine, are amphiphilic and rigid, and have low globularity.
These guidelines were then applied to convert deoxynybomycin, a natural product
that is active only against Gram-positive organisms, into an antibiotic with
activity against a diverse panel of multi-drug-resistant Gram-negative pathogens.
We anticipate that these findings will aid in the discovery and development of
antibiotics against Gram-negative bacteria.
PMID- 28489820
TI - Discovery of nitrate-CPK-NLP signalling in central nutrient-growth networks.
AB - Nutrient signalling integrates and coordinates gene expression, metabolism and
growth. However, its primary molecular mechanisms remain incompletely understood
in plants and animals. Here we report unique Ca2+ signalling triggered by nitrate
with live imaging of an ultrasensitive biosensor in Arabidopsis leaves and roots.
A nitrate-sensitized and targeted functional genomic screen identifies subgroup
III Ca2+-sensor protein kinases (CPKs) as master regulators that orchestrate
primary nitrate responses. A chemical switch with the engineered mutant
CPK10(M141G) circumvents embryo lethality and enables conditional analyses of
cpk10 cpk30 cpk32 triple mutants to define comprehensive nitrate-associated
regulatory and developmental programs. Nitrate-coupled CPK signalling
phosphorylates conserved NIN-LIKE PROTEIN (NLP) transcription factors to specify
the reprogramming of gene sets for downstream transcription factors,
transporters, nitrogen assimilation, carbon/nitrogen metabolism, redox,
signalling, hormones and proliferation. Conditional cpk10 cpk30 cpk32 and nlp7
mutants similarly impair nitrate-stimulated system-wide shoot growth and root
establishment. The nutrient-coupled Ca2+ signalling network integrates
transcriptome and cellular metabolism with shoot-root coordination and
developmental plasticity in shaping organ biomass and architecture.
PMID- 28489821
TI - Whole-brain serial-section electron microscopy in larval zebrafish.
AB - High-resolution serial-section electron microscopy (ssEM) makes it possible to
investigate the dense meshwork of axons, dendrites, and synapses that form
neuronal circuits. However, the imaging scale required to comprehensively
reconstruct these structures is more than ten orders of magnitude smaller than
the spatial extents occupied by networks of interconnected neurons, some of which
span nearly the entire brain. Difficulties in generating and handling data for
large volumes at nanoscale resolution have thus restricted vertebrate studies to
fragments of circuits. These efforts were recently transformed by advances in
computing, sample handling, and imaging techniques, but high-resolution
examination of entire brains remains a challenge. Here, we present ssEM data for
the complete brain of a larval zebrafish (Danio rerio) at 5.5 days post
fertilization. Our approach utilizes multiple rounds of targeted imaging at
different scales to reduce acquisition time and data management requirements. The
resulting dataset can be analysed to reconstruct neuronal processes, permitting
us to survey all myelinated axons (the projectome). These reconstructions enable
precise investigations of neuronal morphology, which reveal remarkable bilateral
symmetry in myelinated reticulospinal and lateral line afferent axons. We further
set the stage for whole-brain structure-function comparisons by co-registering
functional reference atlases and in vivo two-photon fluorescence microscopy data
from the same specimen. All obtained images and reconstructions are provided as
an open-access resource.
PMID- 28489823
TI - Corrigendum: The genome of Chenopodium quinoa.
AB - This corrects the article DOI: 10.1038/nature21370.
PMID- 28489824
TI - Corrigendum: Earth's first stable continents did not form by subduction.
AB - This corrects the article DOI: 10.1038/nature21383.
PMID- 28489822
TI - TRAF2 and OTUD7B govern a ubiquitin-dependent switch that regulates mTORC2
signalling.
AB - The mechanistic target of rapamycin (mTOR) has a key role in the integration of
various physiological stimuli to regulate several cell growth and metabolic
pathways. mTOR primarily functions as a catalytic subunit in two structurally
related but functionally distinct multi-component kinase complexes, mTOR complex
1 (mTORC1) and mTORC2 (refs 1, 2). Dysregulation of mTOR signalling is associated
with a variety of human diseases, including metabolic disorders and cancer. Thus,
both mTORC1 and mTORC2 kinase activity is tightly controlled in cells. mTORC1 is
activated by both nutrients and growth factors, whereas mTORC2 responds primarily
to extracellular cues such as growth-factor-triggered activation of PI3K
signalling. Although both mTOR and GbetaL (also known as MLST8) assemble into
mTORC1 and mTORC2 (refs 11, 12, 13, 14, 15), it remains largely unclear what
drives the dynamic assembly of these two functionally distinct complexes. Here we
show, in humans and mice, that the K63-linked polyubiquitination status of GbetaL
dictates the homeostasis of mTORC2 formation and activation. Mechanistically, the
TRAF2 E3 ubiquitin ligase promotes K63-linked polyubiquitination of GbetaL, which
disrupts its interaction with the unique mTORC2 component SIN1 (refs 12, 13, 14)
to favour mTORC1 formation. By contrast, the OTUD7B deubiquitinase removes
polyubiquitin chains from GbetaL to promote GbetaL interaction with SIN1,
facilitating mTORC2 formation in response to various growth signals. Moreover,
loss of critical ubiquitination residues in GbetaL, by either K305R/K313R
mutations or a melanoma-associated GbetaL(DeltaW297) truncation, leads to
elevated mTORC2 formation, which facilitates tumorigenesis, in part by activating
AKT oncogenic signalling. In support of a physiologically pivotal role for OTUD7B
in the activation of mTORC2/AKT signalling, genetic deletion of Otud7b in mice
suppresses Akt activation and Kras-driven lung tumorigenesis in vivo.
Collectively, our study reveals a GbetaL-ubiquitination-dependent switch that
fine-tunes the dynamic organization and activation of the mTORC2 kinase under
both physiological and pathological conditions.
PMID- 28489827
TI - Cancer: Tumours build their niche.
PMID- 28489826
TI - A rhodopsin in the brain functions in circadian photoentrainment in Drosophila.
AB - Animals partition their daily activity rhythms through their internal circadian
clocks, which are synchronized by oscillating day-night cycles of light. The
fruitfly Drosophila melanogaster senses day-night cycles in part through
rhodopsin-dependent light reception in the compound eye and photoreceptor cells
in the Hofbauer-Buchner eyelet. A more noteworthy light entrainment pathway is
mediated by central pacemaker neurons in the brain. The Drosophila circadian
clock is extremely sensitive to light. However, the only known light sensor in
pacemaker neurons, the flavoprotein cryptochrome (Cry), responds only to high
levels of light in vitro. These observations indicate that there is an additional
light-sensing pathway in fly pacemaker neurons. Here we describe a previously
uncharacterized rhodopsin, Rh7, which contributes to circadian light entrainment
by circadian pacemaker neurons in the brain. The pacemaker neurons respond to
violet light, and this response depends on Rh7. Loss of either cry or rh7 caused
minor defects in photoentrainment, whereas loss of both caused profound
impairment. The circadian photoresponse to constant light was impaired in rh7
mutant flies, especially under dim light. The demonstration that Rh7 functions in
circadian pacemaker neurons represents, to our knowledge, the first role for an
opsin in the central brain.
PMID- 28489825
TI - Intratumoural heterogeneity generated by Notch signalling promotes small-cell
lung cancer.
AB - The Notch signalling pathway mediates cell fate decisions and is tumour
suppressive or oncogenic depending on the context. During lung development, Notch
pathway activation inhibits the differentiation of precursor cells to a
neuroendocrine fate. In small-cell lung cancer, an aggressive neuroendocrine lung
cancer, loss-of-function mutations in NOTCH genes and the inhibitory effects of
ectopic Notch activation indicate that Notch signalling is tumour suppressive.
Here we show that Notch signalling can be both tumour suppressive and pro
tumorigenic in small-cell lung cancer. Endogenous activation of the Notch pathway
results in a neuroendocrine to non-neuroendocrine fate switch in 10-50% of tumour
cells in a mouse model of small-cell lung cancer and in human tumours. This
switch is mediated in part by Rest (also known as Nrsf), a transcriptional
repressor that inhibits neuroendocrine gene expression. Non-neuroendocrine Notch
active small-cell lung cancer cells are slow growing, consistent with a tumour
suppressive role for Notch, but these cells are also relatively chemoresistant
and provide trophic support to neuroendocrine tumour cells, consistent with a pro
tumorigenic role. Importantly, Notch blockade in combination with chemotherapy
suppresses tumour growth and delays relapse in pre-clinical models. Thus, small
cell lung cancer tumours generate their own microenvironment via activation of
Notch signalling in a subset of tumour cells, and the presence of these cells may
serve as a biomarker for the use of Notch pathway inhibitors in combination with
chemotherapy in select patients with small-cell lung cancer.
PMID- 28489828
TI - Ageing: Tools to eliminate senescent cells.
PMID- 28489830
TI - [Clinical and laboratory characteristics of patients with pulmonary hypertension
and pulmonary vascular complications hospitalized at the Instituto Nacional de
Salud del Nino].
AB - : The hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPHN) are
distinct pulmonary vascular complications of portal hypertension (PHT) and are
associated with increased morbidity and mortality. OBJECTIVES: To describe the
clinical and laboratory characteristics of patients with pulmonary hypertension
and pulmonary vascular complications hospitalized at the Instituto Nacional de
Salud del Nino. MATERIALS AND METHODS: We included patients with HTP hospitalized
from January 2012 to June 2013 and that during its evolution progressed with SHP
or HTPP. For analysis, they were divided into a first group of patients with
liver cirrhosis and a second group with extrahepatic portal vein obstruction.
RESULTS: Of 22 patients with HPT 45.5% were male and the age range was between 1
month and 17 years. The etiology in the group of cirrhosis (n=14) was: autoimmune
hepatitis (35.7%), cryptogenic cirrhosis (35.7%), inborn error of metabolism
(14.3%), chronic viral hepatitis C (7.15%) virus and atresia extra-hepatic bile
ducts (7.15%). Pulmonary vascular complications more frequently occurred in
patients with liver cirrhosis (1 case of HPS and a case of PPHTN). They most
often dyspnea, asthenia, edema, malnutrition, ascites, hypersplenism and
gastrointestinal bleeding from esophageal varices was found. Also, they had
elevated ALT values, alkaline phosphatase and serum albumin values decreased.
CONCLUSIONS: In children with pulmonary hypertension, pulmonary vascular
complications are rare. In the evaluation of these patients pulse oximetry should
be included to detect hypoxemia and ubsequently a Doppler echocardiography and
contrast echocardiography necessary. Dueto the finding of systolic pulmonary
hypertension it is necessary to perform right heart catheterization.
PMID- 28489831
TI - [Relationship between the frequency of work-related stress and prevalence of
functional dyspepsia in Lima Geriatric Army Hospital].
AB - OBJECTIVE: To determine the relationship between the frequency of work-related
stress and prevalence of functional dyspepsia in a sample of 218 military older
50 years in 2010 in Lima Military Hospital Geriatric. MATERIALS AND METHODS:
Descriptive and explanatory study and for the data collection on stress, were
used the Vital Events Scale Holmes-Rahe and clinical records for clinical and
upper endoscopy registration that comply the criteria of Rome III for functional
dyspepsia. For processing and data analysis the statistical software package SPSS
(Statistical Package for Social Sciences) was used. RESULTS: 100% of military
showed some level of work stress during the study year; thus, 36.7% had a high
level, 31.2% medium or moderate level, and 32.1% had low stress level; these
percentages medium and high stress levels accounted for 67.9%. These results
establish that job stress is a common discomfort in the study population
(tabulated Chi2 = 3.841, chi2 observed = 27,908). Regarding functional dyspepsia
prevalence of 37.2%, which indicates that it is a common condition in those
military (tabular Z = 1.96, Z c = 9.163) it was determined. CONCLUSIONS: There is
a significant relationship between the frequency of work-related stress and
prevalence of functional dyspepsia in military activity in older than 50 years
(tabulated Chi2 = 5.991, chi2 observed = 28,878, contingency coefficient =
0.342).
PMID- 28489832
TI - Caustic ingestion in children in south of Iran. Retrospective study from Shiraz -
Iran.
AB - : Caustic ingestion is a major health concern in both developed and developing
countries, that may lead to serious esophageal injury. The clinical presentation
of caustic ingestion in children vary from asymptomatic to serious and fatal
sequelae, such as perforation and stricture formation. OBJECTIVE: Due to the lack
of a comprehensive study in our area, this study has evaluated clinical and
endoscopic manifestations and complications of caustic ingestion in children in
south of Iran. MATERIALS AND METHODS: In this retrospective study, we reviewed 75
children with caustic ingestion who admitted in Nemazee Hospital of Shiraz
University of Medical Science during 6 years (2006-2011). Sign and symptoms were
recorded for each case. RESULTS: The most common symptoms were dysphagia, oral
lesions, vomiting, and drooling. Esophageal injuries were detected in both acid
and alkali ingestion, but gastric injuries was significantly more in acid
ingestion. During follow up period, 20% of all cases developed esophageal
stricture. CONCLUSION: Dysphagia, oral lesions, vomiting, and drooling were the
most common findings.Esophageal stricture was found in 20% of cases during 3
months of follow up.
PMID- 28489833
TI - [Impact of infectious postoperative complications in the long term survival of
patients gastrectomized for gastric carcinoma with curative intent].
AB - OBJECTIVE: To determine the impact of postoperative infectious complications in
the long term survival of patients gastrectomized for gastric carcinoma with
curative intent. MATERIALS AND METHODS: The present cohort study evaluated a
series of 79 patients diagnosed with resectable advanced gastric carcinoma with
curative intent. They were grouped in: Group A (N=28): patients with
postoperative infectious complications and Group B (N=51): patients who did not
develop postoperative infectious complications. The study covered the years 2008
2013. RESULTS: In group A, the survival rates at 1, 3 and 5 years was 74%, 74%
and 47.6% respectively. In group B, the survival rates at 1, 3 and 5 years was
80.3%, 56% and 49.8% respectively (p=0.365). The main postoperative infectious
complications not related to the surgical technique were pneumonia (20.3%),
followed by urinary tract infection (3.8%). The main postoperative infectious
complications related to surgical technique was sepsis (n=5), two of which were
related to dehiscence esophagojejunal anastomosis, two bye gastroyeyunal fistula,
another bye enterocutaneous fistula and one patient who presented abscess and
necrosis peripancreatic's tissue. CONCLUSIONS: There was no impact on survival at
5 years in patients with postoperative infectious complications after gastrectomy
with curative intent. However, further studies should be carried over.
PMID- 28489834
TI - Endoscopic gastrostomy: critical analysis in a regional referral hospital.
AB - INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) is a safe and effective
endoscopic surgical procedure for enteral access and gastrointestinal
decompression, and it is an excellent alternative to surgical gastrostomy. There
are various clinical indications and these mainly include the need for prolonged
enteral nutritional support due to complications from neurological, geriatric and
oncological diseases and decompression of the gastrointestinal tract. Although
safe and effective, a number of possible complications relating to the time
(early or late complications) and severity (minor or major complications) may
occur. OBJECTIVE: To evaluate the indications and complications relating to PEG
among selected patients at the digestive endoscopy service of a regional referral
hospital. MATERIALS AND METHODS: A retrospective study on patients who underwent
PEG between May 2013 and April 2015 was conducted. The patients were identified
through searching the medical records and using a standardized data form.
RESULTS: 53 cases were analyzed. The average age was 70.47 years and 60.37% of
the patients werewomen. The main indication identified was the need for enteral
nutritional support, and 73.58% of these indications were derived from
neurological complications, 15.09% from geriatric complications and 9.43% from
oncological complications and 1.88% were due to gastrointestinal decompression.
Complications occurred in 24.52% of the cases: 23.07% were major and 76.93% were
minor. Regarding the time, there were eight cases of late complications and five
of early complications. CONCLUSION: PEG was shown to be an effective and safe
method for enteral access. The indication and complication rates were similar to
those reported in the literature.
PMID- 28489835
TI - [Knowing an infrequent complication of endoscopic retrograde
cholangiopancreatography].
AB - OBJECTIVE: Describe the clinical and tomographic characteristics in relation to
the extra peritoneal distribution of collections and air in patients with
periampullary perforation after performing endoscopic retrograde
cholangiopancreatography (ERCP) with or without sphincterotomy. MATERIALS AND
METHODS: Observational, descriptive study in patients with periampullary
perforation after ERCP with or without sphincterotomy, treated in the Pancreas
Surgery Service at Edgardo Rebagliati Martins Hospital, Lima, Peru between
January 2013 and January 2015. RESULTS: Ten patients with periampullary
perforation after ERCP were included. 40% were male. The mean age was 47.2 years.
100% showed abdominal pain, fever 70%, 60% had jaundice, oral intolerance and
vomiting. In 100% of cases the description of the procedure was for
choledocolithiasis. Difficult cannulation is described in 80% of cases. Air or
fluid was found in 90% in the right anterior pararenal space and the right
perirenal, and the place where air or liquid is distributed less frequently was
right extraperitoneal pelvis with 20%, in no caserevealed air in the mediastinum.
CONCLUSIONS: The finding of a liquid collection and / or air in the
retroperitoneal space right after ERCP without further involvement of the
pancreatic gland should make us think of periampullary perforation, especially if
you are in the right anterior pararenal space and perirenal space. This entity we
call bilioretroperitoneo.
PMID- 28489836
TI - Epidemiological aspects of endoscopic resections of colorectal polyps in patients
at an endoscopy training center in the Santos region, Brasil.
AB - INTRODUCTION: Colorectal polyps are structures that project from the surface of
the mucosal layer of the large intestine. They are classified as neoplastic or
non-neoplastic. Early detection of pre-neoplastic lesions is important for
preventing colorectal cancer. These can be resected so as to decrease the
morbidity and mortality rates. Colonoscopy is the gold-standard procedure for
diagnosing and resecting precursor lesions. OBJECTIVE: To evaluate the
epidemiological, endoscopic and histological aspects of endoscopic resection of
lesions of the colon and rectum at a training center. MATERIALS AND METHOD: A
search was conducted in the database of our institution covering the period from
January 2011 to July 2014. Cases that underwent endoscopic resection of polyps
and/or colorectal lesions were selection. The following variables were defined:
general data on the patients (age, gender and indication from the examination)
and data on the polypoid lesion (number, histological type and topographic
distribution). RESULTS: 678 lesions were identified in 456 examinations.
Regarding sex, 242 (53.1%) were female and 214 (46.9%) were male. The mean age
was 64.54 years, with extremes of 5 and 94 years. The most frequent locations
were the rectum (21%) and sigmoid (20%). Histologically, 34.7% were hyperplastic
polyps and 58.9% were adenomatous polyps, of which 74.1% were tubular, 10.6%
tubulovillous, 2% villous and 13% indeterminate; and 1.7% were adenocarcinomas.
In 65.4% of the cases, the examination showed that only one polyps was present,
while 34.6% had two or more lesions. CONCLUSION: In our clinic, with a mean of
250 examinations/month, the parameters evaluated were compatible with the results
reported in the literature.
PMID- 28489837
TI - [Validation of the rapid urease test for the detection of Helicobacter pylori in
a Peruvian hospital].
AB - OBJECTIVE: To validate a rapid urease test (RUT) in Cayetano Heredia Hospital
(HCH) in Lima, Peru. MATERIALS AND METHODS: This is a prospective observational
study that included 181 patients over 18 years old with dyspeptic symptoms. All
of them underwent upper gastrointestinal endoscopy at the Department of
Gastroenterology at HCH. They had not received, during the last four weeks,
proton pump inhibitors (PPIs), bismuth or antibiotics. Two biopsies of antrum
were taken, one to perform the TRU (Sensibacter pylori test(r)) and the other one
for pathology, in order to determine by both methods the presence of H. pylori
infection. TRU's results were compared with pathology s (gold standard). RESULTS:
181 patients, average age 52.8+/-13.5 years, were evaluated. The sensitivity,
specificity, negative predictive value (NPV), positive predictive value (PPV) at
20 minutes were 86.8%, 98.5%, 81.5% and 99% and at 24 hours 97.3%, 99.5%, 95.7% y
99.1% respectively. CONCLUSION: The rapid urease test is a reliable, accessible
and easy to apply test for the diagnosis of H. pylori infection.
PMID- 28489839
TI - [Deregulation of microRNAs in gastric cancer: up regulation by miR-21 and miR
106].
AB - Gastric cancer (GC) exhibits significant rates of mortality worldwide, a
situation that is even more disturbing in Colombia, because it has had
historically high rate for that disease; At regional context we have found that
Boyaca has the second place of gastric cancer mortality rate in the country, with
displeasing numbers. Early detection is critical to the survival of people, so in
this article, major based on world literature search, we show that the microRNA
could be a useful tool for the diagnosis, prognosis and can be designed as
important therapeutic target. Aims to this are demonstrate howmiRNAs are
deregulated during the emergence and development of gastric cancer and how their
biological functions can place them as oncogenes or tumor suppressors; finally,
we showed that two microRNAs (miR-21 and miR-106b) are significantly upregulated
in the disease and may have a pro-oncogenic action, blocking normal cell cycle,
apoptosis and migration.
PMID- 28489838
TI - [Diagnostic and therapeutic approach to small bowel disorders through capsule
endoscopy and double-balloon endoscopy].
AB - Many small bowel disorders represent a great challenge for gastroenterologists
and endoscopists due to the very low rates of success showed by the different
agnosis techniques. The advent of the capsule endoscopy and double-balloon
endoscopy has allowed a total, secure and efficient examination of the small
bowel, which represents a real impact in diagnosis, treatment, and prognosis of
our patients. The capsule endoscopy is a safe, minimally invasive procedure,
which does not need sedation, does not cause pain, and allows the observation of
the totality of the small bowel. Furthermore, the double-balloon endoscopy is the
complementary technique necessary to provide a therapeutic procedure (cauterizing
angiodysplasia, polypectomy, biopsies), and hence achieving resolution of various
disorders.
PMID- 28489840
TI - [Pancreaticoduodenectomy for a solid pseudopapillary tumor of the pancreas in
children].
AB - The solid pseudopapillary tumor of the pancreas (SPT) is a rare neoplasm with low
malignant potential in children. We report the case of a 9 years old child with a
SPT localized in the pancreatic head. She underwent a pancreaticoduodenectomy
(PD) with favorable evolution. The PD in high-volume centers is safe in both
adults and children.
PMID- 28489841
TI - [Colon Paracoccidioidomycosis in a hospital from Lima - Peru: report of 4 cases].
AB - Paracoccidioidomycosis is the most prevalent mycosis in South America.
Mucocutaneous and lymph node involvement is the most frequent affectation of this
disease in our country, with the intestinal commitment rarely reported. We report
4 cases of colonic manifestation with abdominal pain, chronic diarrhea, and
weight loss. The diagnosis was made with biopsy and Gomori stain. The average age
was 29 years old. The colonoscopy showed many ulcers in the ileum distal and
colon. We found VIH as comorbidity in one patient.
PMID- 28489842
TI - [Gastrointestinal bleeding in newborn with hookworm, National Hospital San
Bartolome. Case report].
AB - We present the case of gastrointestinal bleeding uncinariasis in a newborn baby
of 27 days old from anindigenous town of Tangoshiri, located in the province of
La Convencion, department of Cuzco, who enters to the service of neonatology
National Teaching Hospital San Bartolome in Lima, Peru, with decompensated severe
anemia. The baby has melena since the fourth day of his birth, which increased in
the third week of life, with hematocrit of 12%. She was hospitalized, receiving
blood transfusion and she continue with gastrointestinal bleeding, so she
underwent an upper endoscopy that showed multiple larvae Ancylostoma duodenale.
She and her mother were treated with mebendazole. Afterwords they had stool
examinations without the presence of the parasite.
PMID- 28489843
TI - [Non-cirrhotic portal hypertension due to didanosina. A rare case].
AB - Liver involvement is usually seen in patients infected with the human
immunodeficiency virus (HIV), especially in patients coinfected with hepatitis B
or C, in alcohol abuse, etc. However, there is a group of patients who develop
liver involvement and portal hypertension of unspecified cause. Non-cirrhotic
portal hypertension (NCPH) is a liver disorder recently described, but
potentially serious. It has been reported in HIV-infected patients with highly
active antiretroviral therapy (HAART), specifically didanosine (DDI). The
pathophysiology involves the infectious agent (HIV) and its treatment (HAART),
since both generate a pre-hepatic portal venulopathy. Similarly, HIV infection
produces a prothrombotic state by protein S deficiency leading to the
obliteration of small hepatic venules. It has been postulated that DDI as a
cofactor in the pathogenesis of NCPH. All this leads that many of the liver
biopsies show nodular regenerative hyperplasia. We present the case of a HIV
infected patient who was treated with a longstanding DDI. She developed upper
gastrointestinal bleeding (UGB) and ascites due to NCPH, whose diagnosis was
confirmed by biopsy. However, there is no similar study in our country.
PMID- 28489844
TI - Penetrating gastric ulcer as a manifestation of multisystemic tuberculosis.
AB - We present the case of a 30-year old female with a history of abdominal pain,
fever, poor oral tolerance and weight loss for 6 months. An abdominal CT scan
showed marked gastric dilatation due to extrinsic compression from
lymphadenopathies around the second portion of the duodenum. The upper endoscopy
revealed the presence of a penetrating gastric ulcer in the greater curvature.
Biopsies of the lesions showed hystiocytes with granulomatous features and Acid
Fast Bacilli (AFB) positive, and the cultures grew Mycobacterium tuberculosis
sensitive to Isonazid and Rifampin. Subsequently anti-TB regimen was initiated
achieving great clinical and endoscopic improvement.
PMID- 28489845
TI - Caput Medusae due to portal hypertension in schistosomiasis mansoni.
AB - A 62-year-old Brazilian man who lived in endemic areas of tropical diseases had
an episode of hematemesis associated with portal hypertension. He used to swim in
natural ponds during childhood and developed the hepatosplenic form of
schistossomiasis with moderate ascites, in addition to the characteristic
features of abdominal Caput Medusae. The aim of the report is highlight the role
of chronic liver disease and schistossomiasis.
PMID- 28489846
TI - [Gastrointestinal bleeding and acute hepatic failure by leptospirosis: an entity
that should not be forgotten].
AB - Leptospirosis disease is caused by the spirochete Leptospira. It is a worldwide
distribution zoonosis, with predominance in the tropics. In Spain, it is not
frequent but some cases have been noticed especially in humid areas surrounded by
rivers, lakes or ponds, such as Catalonia, Andalucia or the Valencian Community.
It is transmitted by a variety of animals such as cows or rats, that are infected
either by direct contact with these animals or their urine, or indirectly by
consuming or being in contact with water contaminated by their urine. The
clinical manifestations are very variable, being asymptomatic or not very
symptomatic in most of the patients. Unusually, leptospirosis presents with a
first phase with fever, myalgias, liver injury or different organs hemorrhage,
followed by a second phase with the presence of jaundice due to hepatic failure.
Weil's disease is a kind of severe leptospirosis characterized by hepatic failure
with jaundice and acute renal failure, associated with high mortality rates.The
diagnosis is based on serological techniques and DNA detection by PCR. The
treatment consists of life support measures and antibiotic therapy. A patient
with Weil's disease and leptospirosis digestive bleeding is presented, with a
fulminant clinical course. In order to achieve an early diagnosis, the need to
keep this entity in mind must be emphasized, especially in favorable
epidemiological environments as the one of this patient.
PMID- 28489847
TI - [Zinc in the management of diarrhea: adequate for all the pediatric population?]
PMID- 28489848
TI - A coordinated DNA damage response promotes adult quiescent neural stem cell
activation.
AB - Stem and differentiated cells frequently differ in their response to DNA damage,
which can determine tissue sensitivity. By exploiting insight into the spatial
arrangement of subdomains within the adult neural subventricular zone (SVZ) in
vivo, we show distinct responses to ionising radiation (IR) between neural stem
and progenitor cells. Further, we reveal different DNA damage responses between
neonatal and adult neural stem cells (NSCs). Neural progenitors (transit
amplifying cells and neuroblasts) but not NSCs (quiescent and activated) undergo
apoptosis after 2 Gy IR. This response is cell type- rather than proliferation
dependent and does not appear to be driven by distinctions in DNA damage
induction or repair capacity. Moreover, exposure to 2 Gy IR promotes
proliferation arrest and differentiation in the adult SVZ. These 3 responses are
ataxia telangiectasia mutated (ATM)-dependent and promote quiescent NSC (qNSC)
activation, which does not occur in the subdomains that lack progenitors.
Neuroblasts arising post-IR derive from activated qNSCs rather than irradiated
progenitors, minimising damage compounded by replication or mitosis. We propose
that rather than conferring sensitive cell death, apoptosis is a form of rapid
cell death that serves to remove damaged progenitors and promote qNSC activation.
Significantly, analysis of the neonatal (P5) SVZ reveals that although
progenitors remain sensitive to apoptosis, they fail to efficiently arrest
proliferation. Consequently, their repopulation occurs rapidly from irradiated
progenitors rather than via qNSC activation.
PMID- 28489849
TI - Utilizing BMP-2 muteins for treatment of multiple myeloma.
AB - Multiple myeloma (MM) represents a haematological cancer characterized by the
pathological hyper proliferation of antibody-producing B-lymphocytes. Patients
typically suffer from kidney malfunction and skeletal disorders. In the context
of MM, the transforming growth factor beta (TGFbeta) member Activin A was
recently identified as a promoter of both accompanying symptoms. Because studies
have shown that bone morphogenetic protein (BMP)-2-mediated activities are
counteracted by Activin A, we analysed whether BMP2, which also binds to the
Activin A receptors ActRII and ActRIIB but activates the alternative SMAD-1/5/8
pathway, can be used to antagonize Activin A activities, such as in the context
of MM. Therefore three BMP2 derivatives were generated with modified binding
activities for the type II (ActRIIB) and/or type I receptor (BMPRIA) showing
either increased or decreased BMP2 activity. In the context of MM these BMP2
muteins show two functionalities since they act as a) an anti
proliferative/apoptotic agent against neoplastic B-cells, b) as a bone-formation
promoting growth factor. The molecular basis of both activities was shown in two
different cellular models to clearly rely on the properties of the investigated
BMP2 muteins to compete for the binding of Activin A to the Activin type II
receptors. The experimental outcome suggests new therapeutic strategies using
BMP2 variants in the treatment of MM-related pathologies.
PMID- 28489850
TI - Testing the effect of the Himalayan mountains as a physical barrier to gene flow
in Hippophae tibetana Schlect. (Elaeagnaceae).
AB - Hippophae tibetana is a small, dioecious wind-pollinated shrub endemic to the
Tibetan-Qinghai Plateau. It is one of the shrubs that occur at very high
elevations (5250 m a.s.l.). The Himalayan mountains provides a significant
geographical barrier to the Qinghai-Tibetan Plateau, dividing the Himalayan area
into two regions with Nepal to the south and Tibet to the north. There is no
information on how the Himalayan mountains influence gene flow and population
differentiation of alpine plants. In this study, we analyzed eight nuclear
microsatellite markers and cpDNA trnT-trnF regions to test the role of the
Himalayan mountains as a barrier to gene flow between populations of H. tibetana.
We also examined the fine-scale genetic structure within a population of H.
tibetana on the north slope of Mount (Mt.) Everest. For microsatellite analyses,
a total of 241 individuals were sampled from seven populations in our study area
(4 from Nepal, 3 from Tibet), including 121 individuals that were spatially
mapped within a 100 m * 100 m plot. To test for seed flow, the cpDNA trnT-trnF
regions of 100 individuals from 6 populations (4 from Nepal, 2 from Tibet) were
also sequenced. Significant genetic differentiation was detected between the two
regions by both microsatellite and cpDNA data analyses. These two datasets agree
about southern and northern population differentiation, indicating that the
Himalayan mountains represent a barrier to H. tibetana limiting gene flow between
these two areas. At a fine scale, spatial autocorrelation analysis suggests
significant genetic structure within a distance of less than 45 m, which may be
attributed mainly to vegetative reproduction and habitat fragmentation, as well
as limited gene flow.
PMID- 28489852
TI - Recurrent promoter mutations in melanoma are defined by an extended context
specific mutational signature.
AB - Sequencing of whole tumor genomes holds the promise of revealing functional
somatic regulatory mutations, such as those described in the TERT promoter.
Recurrent promoter mutations have been identified in many additional genes and
appear to be particularly common in melanoma, but convincing functional data such
as influence on gene expression has been more elusive. Here, we show that
frequently recurring promoter mutations in melanoma occur almost exclusively at
cytosines flanked by a distinct sequence signature, TTCCG, with TERT as a notable
exception. In active, but not inactive, promoters, mutation frequencies for
cytosines at the 5' end of this ETS-like motif were considerably higher than
expected based on a UV trinucleotide mutational signature. Additional analyses
solidify this pattern as an extended context-specific mutational signature that
mediates an exceptional position-specific vulnerability to UV mutagenesis,
arguing against positive selection. We further use ultra-sensitive amplicon
sequencing to demonstrate that cell cultures exposed to UV light quickly develop
subclonal mutations specifically in affected positions. Our findings have
implications for the interpretation of somatic mutations in regulatory regions,
and underscore the importance of genomic context and extended sequence patterns
to accurately describe mutational signatures in cancer.
PMID- 28489851
TI - Global analysis of double-strand break processing reveals in vivo properties of
the helicase-nuclease complex AddAB.
AB - In bacteria, double-strand break (DSB) repair via homologous recombination is
thought to be initiated through the bi-directional degradation and resection of
DNA ends by a helicase-nuclease complex such as AddAB. The activity of AddAB has
been well-studied in vitro, with translocation speeds between 400-2000 bp/s on
linear DNA suggesting that a large section of DNA around a break site is
processed for repair. However, the translocation rate and activity of AddAB in
vivo is not known, and how AddAB is regulated to prevent excessive DNA
degradation around a break site is unclear. To examine the functions and
mechanistic regulation of AddAB inside bacterial cells, we developed a next
generation sequencing-based approach to assay DNA processing after a site
specific DSB was introduced on the chromosome of Caulobacter crescentus. Using
this assay we determined the in vivo rates of DSB processing by AddAB and found
that putative chi sites attenuate processing in a RecA-dependent manner. This
RecA-mediated regulation of AddAB prevents the excessive loss of DNA around a
break site, limiting the effects of DSB processing on transcription. In sum, our
results, taken together with prior studies, support a mechanism for regulating
AddAB that couples two key events of DSB repair-the attenuation of DNA-end
processing and the initiation of homology search by RecA-thereby helping to
ensure that genomic integrity is maintained during DSB repair.
PMID- 28489853
TI - Novel genes involved in severe early-onset obesity revealed by rare copy number
and sequence variants.
AB - Obesity is a multifactorial disorder with high heritability (50-75%), which is
probably higher in early-onset and severe cases. Although rare monogenic forms
and several genes and regions of susceptibility, including copy number variants
(CNVs), have been described, the genetic causes underlying the disease still
remain largely unknown. We searched for rare CNVs (>100kb in size, altering genes
and present in <1/2000 population controls) in 157 Spanish children with non
syndromic early-onset obesity (EOO: body mass index >3 standard deviations above
the mean at <3 years of age) using SNP array molecular karyotypes. We then
performed case control studies (480 EOO cases/480 non-obese controls) with the
validated CNVs and rare sequence variants (RSVs) detected by targeted
resequencing of selected CNV genes (n = 14), and also studied the inheritance
patterns in available first-degree relatives. A higher burden of gain-type CNVs
was detected in EOO cases versus controls (OR = 1.71, p-value = 0.0358). In
addition to a gain of the NPY gene in a familial case with EOO and attention
deficit hyperactivity disorder, likely pathogenic CNVs included gains of
glutamate receptors (GRIK1, GRM7) and the X-linked gastrin-peptide receptor
(GRPR), all inherited from obese parents. Putatively functional RSVs absent in
controls were also identified in EOO cases at NPY, GRIK1 and GRPR. A patient with
a heterozygous deletion disrupting two contiguous and related genes, SLCO4C1 and
SLCO6A1, also had a missense RSV at SLCO4C1 on the other allele, suggestive of a
recessive model. The genes identified showed a clear enrichment of shared co
expression partners with known genes strongly related to obesity, reinforcing
their role in the pathophysiology of the disease. Our data reveal a higher burden
of rare CNVs and RSVs in several related genes in patients with EOO compared to
controls, and implicate NPY, GRPR, two glutamate receptors and SLCO4C1 in highly
penetrant forms of familial obesity.
PMID- 28489854
TI - Functional and phenotypic evaluation of eosinophils from patients with the acute
form of paracoccidioidomycosis.
AB - BACKGROUND: Eosinophilia is a typical finding of the acute/juvenile form of
paracoccidioidomycosis (PCM), a systemic mycosis endemic in Latin America. This
clinical form is characterized by depressed cellular immune response and
production of Th2 cytokines. Moreover, it has been shown that the increased
number of eosinophils in peripheral blood of patients returns to normal values
after antifungal treatment. However, the role of eosinophils in PCM has never
been evaluated. This study aimed to assess the phenotypic and functional
characteristics of eosinophils in PCM. METHODS/PRINCIPAL FINDINGS: In 15 patients
with the acute form of the disease, we detected expression of MBP, CCL5 (RANTES)
and CCL11 (eotaxin) in biopsies of lymph nodes and liver. In addition, there were
higher levels of chemokines and granule proteins in the peripheral blood of
patients compared to controls. Isolation of eosinophils from blood revealed a
higher frequency of CD69+ and TLR2+ eosinophils in patients compared to controls,
and a lower population of CD80+ cells. We also evaluated the fungicidal capacity
of eosinophils in vitro. Our results revealed that eosinophils from PCM patients
and controls exhibit similar ability to kill P. brasiliensis yeast cells,
although eosinophils of patients were less responsive to IL-5 stimulation than
controls. CONCLUSION/PRINCIPAL FINDINGS: In conclusion, we suggest that
eosinophils might play a role in the host response to fungi and in the
pathophysiology of PCM by inducing an intense and systemic inflammatory response
in the initial phase of the infection.
PMID- 28489855
TI - Haemophilus ducreyi DNA is detectable on the skin of asymptomatic children, flies
and fomites in villages of Papua New Guinea.
AB - BACKGROUND: Haemophilus ducreyi and Treponema pallidum subsp. pertenue are major
causes of leg ulcers in children in Africa and the Pacific Region. We
investigated the presence of DNA (PCR positivity) from these bacteria on
asymptomatic people, flies, and household linens in an endemic setting.
METHODOLOGY/PRINCIPAL FINDINGS: We performed a cross-sectional study in rural
villages of Lihir Island, Papua New Guinea during a yaws elimination campaign.
Participants were asymptomatic subjects recruited from households with cases of
leg ulcers, and from households without cases of leg ulcers. We rubbed swabs on
the intact skin of the leg of asymptomatic individuals, and collected flies and
swabs of environmental surfaces. All specimens were tested by PCR for H. ducreyi
and T. p. pertenue DNA. Of 78 asymptomatic participants that had an adequate
specimen for DNA detection, H. ducreyi-PCR positivity was identified in 16 (21%)
and T. p. pertenue-PCR positivity in 1 (1%). In subgroup analyses, H. ducreyi-PCR
positivity did not differ in participants exposed or not exposed to a case of H.
ducreyi ulcer in the household (24% vs 18%; p = 0.76). Of 17 cultures obtained
from asymptomatic participants, 2 (12%) yielded a definitive diagnosis of H.
ducreyi, proving skin colonization. Of 10 flies tested, 9 (90%) had H. ducreyi
DNA and 5 (50%) had T. p. pertenue DNA. Of 6 bed sheets sampled, 2 (33%) had H.
ducreyi DNA and 1 (17%) had T. p. pertenue DNA. CONCLUSIONS/SIGNIFICANCE: This is
the first time that H. ducreyi DNA and colonization has been demonstrated on the
skin of asymptomatic children and that H. ducreyi DNA and T. p. pertenue DNA has
been identified in flies and on fomites. The ubiquity of H. ducreyi in the
environment is a contributing factor to the spread of the organism.
PMID- 28489856
TI - Randomized trial of stopping or continuing ART among postpartum women with pre
ART CD4 >= 400 cells/mm3.
AB - BACKGROUND: Health benefits of postpartum antiretroviral therapy (ART) for human
immunodeficiency virus (HIV) positive women with high CD4+ T-counts have not been
assessed in randomized trials. METHODS: Asymptomatic, HIV-positive, non
breastfeeding women with pre-ART CD4+ T-cell counts >= 400 cells/mm3 started on
ART during pregnancy were randomized up to 42 days after delivery to continue or
discontinue ART. Lopinavir/ritonavir plus tenofovir/emtricitabine was the
preferred ART regimen. The sample size was selected to provide 88% power to
detect a 50% reduction from an annualized primary event rate of 2.07%. A post-hoc
analysis evaluated HIV/AIDS-related and World Health Organization (WHO) Stage 2
and 3 events. All analyses were intent to treat. RESULTS: 1652 women from 52
sites in Argentina, Botswana, Brazil, China, Haiti, Peru, Thailand and the US
were enrolled (1/2010-11/2014). Median age was 28 years and major racial
categories were Black African (28%), Asian (25%) White (15%). Median entry CD4
count was 696 cells/mm3 (IQR 575-869), median ART exposure prior to delivery was
19 weeks (IQR 13-24) and 94% had entry HIV-1 RNA < 1000 copies/ml. After a median
follow-up of 2.3 years, the primary composite endpoint rate was significantly
lower than expected, and not significantly different between arms (continue arm
0.21 /100 person years(py); discontinue 0.31/100 py, Hazard ratio (HR) 0.68, 95%
CI: 0.19, 2.40). WHO Stage 2 and 3 events were significantly reduced with
continued ART (2.08/100 py vs. 4.36/100 py in the discontinue arm; HR 0.48,
95%CI: 0.33, 0.70). Toxicity rates did not differ significantly between arms.
Among women randomized to continue ART, 189/827 (23%) had virologic failure; of
the 155 with resistance testing, 103 (66%) failed without resistance to their
current regimen, suggesting non-adherence. CONCLUSIONS: Overall, serious clinical
events were rare among young HIV-positive post-partum women with high CD4 cell
counts. Continued ART was safe and was associated with a halving of the rate of
WHO 2/3 conditions. Virologic failure rates were high, underscoring the urgent
need to improve adherence in this population. TRIAL REGISTRATION:
ClinicalTrials.gov NCT00955968.
PMID- 28489858
TI - Knotting and unknotting proteins in the chaperonin cage: Effects of the excluded
volume.
AB - Molecular dynamics simulations are used to explore the effects of chaperonin-like
cages on knotted proteins with very low sequence similarity, different depths of
a knot but with a similar fold, and the same type of topology. The investigated
proteins are VirC2, DndE and MJ0366 with two depths of a knot. A comprehensive
picture how encapsulation influences folding rates is provided based on the
analysis of different cage sizes and temperature conditions. Neither of these two
effects with regard to knotted proteins has been studied by means of molecular
dynamics simulations with coarse-grained structure-based models before. We show
that encapsulation in a chaperonin is sufficient to self-tie and untie small
knotted proteins (VirC2, DndE), for which the equilibrium process is not
accessible in the bulk solvent. Furthermore, we find that encapsulation reduces
backtracking that arises from the destabilisation of nucleation sites, smoothing
the free energy landscape. However, this effect can also be coupled with
temperature rise. Encapsulation facilitates knotting at the early stage of
folding and can enhance an alternative folding route. Comparison to unknotted
proteins with the same fold shows directly how encapsulation influences the free
energy landscape. In addition, we find that as the size of the cage decreases,
folding times increase almost exponentially in a certain range of cage sizes, in
accordance with confinement theory and experimental data for unknotted proteins.
PMID- 28489857
TI - Vitamin D supplementation lowers thrombospondin-1 levels and blood pressure in
healthy adults.
AB - INTRODUCTION: Vitamin D insufficiency, defined as 25-hydroxyvitamin D (25(OH)D)
levels < 75nmol/L is associated with cardio-metabolic dysfunction. Vitamin D
insufficiency is associated with inflammation and fibrosis, but it remains
uncertain whether these anomalies are readily reversible. Therefore, we aimed to
determine the effects of vitamin D supplementation on markers of: 1) nitric oxide
(NO) signaling, 2) inflammation, and 3) fibrosis, in healthy volunteers with mild
hypovitaminosis. METHODS: Healthy volunteers (n = 35) (mean age: 45 +/- 11 years)
with 25(OH)D levels <75nmol/L, received vitamin D supplementation (Ostelin (r)
capsules 2000IU) for 12 weeks. Resting systolic and diastolic blood pressures
(BP) were assessed. Routine biochemistry was examined. Plasma concentrations of
asymmetric dimethylarginine (ADMA), thrombospondin-1 (TSP-1), plasminogen
activator inhibitor-1 (PAI-1), hs-CRP, activin-A, and follistatin-like 3 (FSTL3)
were quantitated. RESULTS: Vitamin D administration for 12 weeks significantly
increased 25-(OH)D levels (48.8 +/- 16 nmol/L to 100.8 +/- 23.7 nmol/L, p<0.001).
There was significant lowering of systolic and diastolic BP, while there was no
significant change in lipid profiles, or fasting insulin. Plasma concentrations
of ADMA, hs-CRP, PAI-1, activin A, and FSTL-3 did not change with vitamin D
supplementation. However, there was a marked reduction of TSP-1 (522.7 +/- 379.8
ng/mL vs 206.7 +/- 204.5 ng/mL, p<0.001). CONCLUSIONS: Vitamin D supplementation
in vitamin D insufficient, but otherwise healthy individuals markedly decreased
TSP-1 levels and blood pressure. Since TSP-1 suppresses signaling of NO, it is
possible that the fall in BP is engendered by restoration of NO effect.
PMID- 28489859
TI - An R2R3-type MYB transcription factor, GmMYB29, regulates isoflavone biosynthesis
in soybean.
AB - Isoflavones comprise a group of secondary metabolites produced almost exclusively
by plants in the legume family, including soybean [Glycine max (L.) Merr.]. They
play vital roles in plant defense and have many beneficial effects on human
health. Isoflavone content is a complex quantitative trait controlled by multiple
genes, and the genetic mechanisms underlying isoflavone biosynthesis remain
largely unknown. Via a genome-wide association study (GWAS), we identified 28
single nucleotide polymorphisms (SNPs) that are significantly associated with
isoflavone concentrations in soybean. One of these 28 SNPs was located in the 5'
untranslated region (5'-UTR) of an R2R3-type MYB transcription factor, GmMYB29,
and this gene was thus selected as a candidate gene for further analyses. A
subcellular localization study confirmed that GmMYB29 was located in the nucleus.
Transient reporter gene assays demonstrated that GmMYB29 activated the IFS2
(isoflavone synthase 2) and CHS8 (chalcone synthase 8) gene promoters.
Overexpression and RNAi-mediated silencing of GmMYB29 in soybean hairy roots
resulted in increased and decreased isoflavone content, respectively. Moreover, a
candidate-gene association analysis revealed that 11 natural GmMYB29
polymorphisms were significantly associated with isoflavone contents, and
regulation of GmMYB29 expression could partially contribute to the observed
phenotypic variation. Taken together, these results provide important genetic
insights into the molecular mechanisms underlying isoflavone biosynthesis in
soybean.
PMID- 28489860
TI - Rediscovery of the enigmatic fungus-farming ant "Mycetosoritis" asper Mayr
(Hymenoptera: Formicidae): Implications for taxonomy, phylogeny, and the
evolution of agriculture in ants.
AB - We report the rediscovery of the exceedingly rarely collected and enigmatic
fungus-farming ant species Mycetosoritis asper. Since the description of the type
specimen in 1887, only four additional specimens are known to have been added to
the world's insect collections. Its biology is entirely unknown and its
phylogenetic position within the fungus-farming ants has remained puzzling due to
its aberrant morphology. In 2014 we excavated and collected twenty-one colonies
of M. asper in the Floresta Nacional de Chapeco in Santa Catarina, Brazil. We
describe here for the first time the male and larva of the species and complement
the previous descriptions of both the queen and the worker. We describe, also for
the first time, M. asper biology, nest architecture, and colony demographics, and
identify its fungal cultivar. Molecular phylogenetic analyses indicate that both
M. asper and M. clorindae are members of the genus Cyphomyrmex, which we show to
be paraphyletic as currently defined. More precisely, M. asper is a member of the
Cyphomyrmex strigatus group, which we also show to be paraphyletic with respect
to the genus Mycetophylax. Based on these results, and in the interest of
taxonomic stability, we transfer the species M. asper, M. clorindae, and all
members of the C. strigatus group to the genus Mycetophylax, the oldest available
name for this clade. Based on ITS sequence data, Mycetophylax asper practices
lower agriculture, cultivating a fungal species that belongs to lower-attine
fungal Clade 2, subclade F.
PMID- 28489861
TI - Prognostic value of lncRNA SOX2OT for Chinese cancer patients: A meta-analysis.
AB - SOX2OT has been demonstrated to be aberrantly expressed in several types of
cancer and maybe serve as a prognostic marker for cancer patients. However, most
individual studies have been limited by small sample sizes and controversial
results. Therefore, the present meta-analysis was conducted to analyze available
data to reveal the potential clinical application of SOX2OT on cancer prognosis,
tumor progression, distance metastasis and lymph node metastasis. Up to February
20, 2017, literature collections were conducted by comprehensive searching
electronic databases, including Cochrane Library, PubMed, Embase, BioMed Central,
Springer, ScienceDirect, ISI Web of Knowledge, together with three Chinese
databases: China National Knowledge Internet (CNKI), Weipu and Wanfang. The
hazard ratios (HR) with 95% confidence interval (95% CI) were calculated to
assess the strength of the association. Five studies with a total of 481 cancer
patients were included in the present meta-analysis. The results indicated that
elevated SOX2OT significantly predicted unfavorable overall survival (OS) (HR =
2.44, 95% CI: 1.75-3.39, P<0.0001) and tumor progression (III/IV vs. I/II: HR
1.62, 95%CI: 1.30-2.02, P<0.0001), but failed to predict distant metastasis (HR:
3.30, 95%CI: 0.74-14.61, P = 0.12) and lymph node metastasis (HR: 1.29, 95% CI:
0.87-1.91, P = 0.21). The results revealed that SOX2OT expression level was an
independent prognostic biomarker for OS and tumor progression in Chinese cancer
patients.
PMID- 28489864
TI - Personality in the cockroach Diploptera punctata: Evidence for stability across
developmental stages despite age effects on boldness.
AB - Despite a recent surge in the popularity of animal personality studies and their
wide-ranging associations with various aspects of behavioural ecology, our
understanding of the development of personality over ontogeny remains poorly
understood. Stability over time is a central tenet of personality; ecological
pressures experienced by an individual at different life stages may, however,
vary considerably, which may have a significant effect on behavioural traits.
Invertebrates often go through numerous discrete developmental stages and
therefore provide a useful model for such research. Here we test for both
differential consistency and age effects upon behavioural traits in the
gregarious cockroach Diploptera punctata by testing the same behavioural traits
in both juveniles and adults. In our sample, we find consistency in boldness,
exploration and sociality within adults whilst only boldness was consistent in
juveniles. Both boldness and exploration measures, representative of risk-taking
behaviour, show significant consistency across discrete juvenile and adult
stages. Age effects are, however, apparent in our data; juveniles are
significantly bolder than adults, most likely due to differences in the
ecological requirements of these life stages. Size also affects risk-taking
behaviour since smaller adults are both bolder and more highly explorative.
Whilst a behavioural syndrome linking boldness and exploration is evident in
nymphs, this disappears by the adult stage, where links between other behavioural
traits become apparent. Our results therefore indicate that differential
consistency in personality can be maintained across life stages despite age
effects on its magnitude, with links between some personality traits changing
over ontogeny, demonstrating plasticity in behavioural syndromes.
PMID- 28489862
TI - Novel genes associated with enhanced motility of Escherichia coli ST131.
AB - Uropathogenic Escherichia coli (UPEC) is the cause of ~75% of all urinary tract
infections (UTIs) and is increasingly associated with multidrug resistance. This
includes UPEC strains from the recently emerged and globally disseminated
sequence type 131 (ST131), which is now the dominant fluoroquinolone-resistant
UPEC clone worldwide. Most ST131 strains are motile and produce H4-type flagella.
Here, we applied a combination of saturated Tn5 mutagenesis and transposon
directed insertion site sequencing (TraDIS) as a high throughput genetic screen
and identified 30 genes associated with enhanced motility of the reference ST131
strain EC958. This included 12 genes that repress motility of E. coli K-12, four
of which (lrhA, ihfA, ydiV, lrp) were confirmed in EC958. Other genes represented
novel factors that impact motility, and we focused our investigation on
characterisation of the mprA, hemK and yjeA genes. Mutation of each of these
genes in EC958 led to increased transcription of flagellar genes (flhD and fliC),
increased expression of the FliC flagellin, enhanced flagella synthesis and a
hyper-motile phenotype. Complementation restored all of these properties to wild
type level. We also identified Tn5 insertions in several intergenic regions
(IGRs) on the EC958 chromosome that were associated with enhanced motility; this
included flhDC and EC958_1546. In both of these cases, the Tn5 insertions were
associated with increased transcription of the downstream gene(s), which resulted
in enhanced motility. The EC958_1546 gene encodes a phage protein with similarity
to esterase/deacetylase enzymes involved in the hydrolysis of sialic acid
derivatives found in human mucus. We showed that over-expression of EC958_1546
led to enhanced motility of EC958 as well as the UPEC strains CFT073 and UTI89,
demonstrating its activity affects the motility of different UPEC strains.
Overall, this study has identified and characterised a number of novel factors
associated with enhanced UPEC motility.
PMID- 28489863
TI - Combining phylogenetic and demographic inferences to assess the origin of the
genetic diversity in an isolated wolf population.
AB - The survival of isolated small populations is threatened by both demographic and
genetic factors. Large carnivores declined for centuries in most of Europe due to
habitat changes, overhunting of their natural prey and direct persecution.
However, the current rewilding trends are driving many carnivore populations to
expand again, possibly reverting the erosion of their genetic diversity. In this
study we reassessed the extent and origin of the genetic variation of the Italian
wolf population, which is expanding after centuries of decline and isolation. We
genotyped wolves from Italy and other nine populations at four mtDNA regions
(control-region, ATP6, COIII and ND4) and 39 autosomal microsatellites. Results
of phylogenetic analyses and assignment procedures confirmed in the Italian
wolves a second private mtDNA haplotype, which belongs to a haplogroup
distributed mostly in southern Europe. Coalescent analyses showed that the unique
mtDNA haplotypes in the Italian wolves likely originated during the late
Pleistocene. ABC simulations concordantly showed that the extant wolf populations
in Italy and in south-western Europe started to be isolated and declined right
after the last glacial maximum. Thus, the standing genetic variation in the
Italian wolves principally results from the historical isolation south of the
Alps.
PMID- 28489865
TI - Awareness, treatment, and control of hypertension is low among adults in Aksum
town, northern Ethiopia: A sequential quantitative-qualitative study.
AB - INTRODUCTION: Hypertension is a major risk factor of cardiovascular diseases
which are the leading causes of deaths from chronic non-communicable diseases in
Ethiopia. However, little is documented in the issue. Therefore, this study aimed
to assess the prevalence, associated factors, awareness, treatment and control of
hypertension among adults 18 years old or above in Aksum town, Tigray region,
North Ethiopia. METHODS: A sequential quantitative-qualitative study was
conducted among adults aged 18 years and above in Aksum town. A multi stage
sampling procedure was used to select the study participants for the quantitative
study whilst convenience sampling technique was used for the qualitative part. A
pre-tested and structured questionnaire was used to collect quantitative data,
and an interview guide was used to collect the qualitative data. The logistic
regression model was fitted to identify factors independently associated with
hypertension using SPSS Version 20. P-values of < 0.05 were considered
statistically significant. For the qualitative data, iterative hearing of the
discussions verbatim interpretation was followed by categorizing similar ideas
into themes and finally triangulated with the quantitative results. RESULTS: The
overall prevalence of hypertension was 16.5% (95% CI: 13.4, 20.0). Awareness,
treatment and control of hypertension were 43%, 2.1% and 18.2%, respectively.
Being unable to read and write [AOR = 4.73, 95% CI:1.11, 20.23], not consuming
fruit [AOR = 4.31, 95% CI:1.74, 10.66], being physically inactive [AOR = 20.11,
95% CI:8.75, 6.20], not knowing physical inactivity is a risk factor of
hypertension [AOR = 3.57, 95% CI: 1.69, 7.69] and being overweight/obese [AOR =
9.2, 95% CI:4.54, 18.67] were significantly associated with hypertension.
Remarkably, all identified hypertensive cases were linked to the nearby hospital
for confirmation of diagnosis, care and follow-up and all of them were found to
be hypertensive. This suggests that implementing primary health care approach
integrated with the urban health extension package may be effective in the
prevention and control of hypertension in poor settings. CONCLUSION AND
RECOMMENDATION: Prevalence of hypertension among adults was very high, but
awareness, treatment and control of hypertension was very low. Being unable to
read and write, not consuming fruit, being physically inactive,
overweight/obesity and not knowing physical inactivity is a risk factor for
hypertension were independently associated with hypertension. Policy makers need
to consider integrating prevention and control of hypertension with health
extension package. Appropriate information, education and communication
strategies should also be designed and implemented to avoid unhealthy lifestyles
and promote healthy practices.
PMID- 28489866
TI - Magmatic evolution of Panama Canal volcanic rocks: A record of arc processes and
tectonic change.
AB - Volcanic rocks along the Panama Canal present a world-class opportunity to
examine the relationship between arc magmatism, tectonic forcing, wet and dry
magmas, and volcanic structures. Major and trace element geochemistry of Canal
volcanic rocks indicate a significant petrologic transition at 21-25 Ma.
Oligocene Bas Obispo Fm. rocks have large negative Nb-Ta anomalies, low HREE,
fluid mobile element enrichments, a THI of 0.88, and a H2Ocalc of >3 wt. %. In
contrast, the Miocene Pedro Miguel and Late Basalt Fm. exhibit reduced Nb-Ta
anomalies, flattened REE curves, depleted fluid mobile elements, a THI of 1.45, a
H2Ocalc of <1 wt. %, and plot in mid-ocean ridge/back-arc basin fields.
Geochemical modeling of Miocene rocks indicates 0.5-0.1 kbar crystallization
depths of hot (1100-1190 degrees C) magmas in which most compositional diversity
can be explained by fractional crystallization (F = 0.5). However, the most
silicic lavas (Las Cascadas Fm.) require an additional mechanism, and
assimilation-fractional-crystallization can reproduce observed compositions at
reasonable melt fractions. The Canal volcanic rocks, therefore, change from
hydrous basaltic pyroclastic deposits typical of mantle-wedge-derived magmas, to
hot, dry bi-modal magmatism at the Oligocene-Miocene boundary. We suggest the
primary reason for the change is onset of arc perpendicular extension localized
to central Panama. High-resolution mapping along the Panama Canal has revealed a
sequence of inward dipping maar-diatreme pyroclastic pipes, large basaltic sills,
and bedded silicic ignimbrites and tuff deposits. These volcanic bodies intrude
into the sedimentary Canal Basin and are cut by normal and subsequently strike
slip faults. Such pyroclastic pipes and basaltic sills are most common in
extensional arc and large igneous province environments. Overall, the change in
volcanic edifice form and geochemistry are related to onset of arc perpendicular
extension, and are consistent with the idea that Panama arc crust fractured
during collision with South America forming the observed Canal extensional zone.
PMID- 28489867
TI - A shape-based inter-layer contours correspondence method for ICT-based reverse
engineering.
AB - The correspondence of a stack of planar contours in ICT (industrial computed
tomography)-based reverse engineering, a key step in surface reconstruction, is
difficult when the contours or topology of the object are complex. Given the
regularity of industrial parts and similarity of the inter-layer contours, a
specialized shape-based inter-layer contours correspondence method for ICT-based
reverse engineering was presented to solve the above problem based on the
vectorized contours. In this paper, the vectorized contours extracted from the
slices consist of three graphical primitives: circles, arcs and segments. First,
the correspondence of the inter-layer primitives is conducted based on the
characteristics of the primitives. Second, based on the corresponded primitives,
the inter-layer contours correspond with each other using the proximity rules and
exhaustive search. The proposed method can make full use of the shape information
to handle industrial parts with complex structures. The feasibility and
superiority of this method have been demonstrated via the related experiments.
This method can play an instructive role in practice and provide a reference for
the related research.
PMID- 28489868
TI - Predicting and understanding law-making with word vectors and an ensemble model.
AB - Out of nearly 70,000 bills introduced in the U.S. Congress from 2001 to 2015,
only 2,513 were enacted. We developed a machine learning approach to forecasting
the probability that any bill will become law. Starting in 2001 with the 107th
Congress, we trained models on data from previous Congresses, predicted all bills
in the current Congress, and repeated until the 113th Congress served as the
test. For prediction we scored each sentence of a bill with a language model that
embeds legislative vocabulary into a high-dimensional, semantic-laden vector
space. This language representation enables our investigation into which words
increase the probability of enactment for any topic. To test the relative
importance of text and context, we compared the text model to a context-only
model that uses variables such as whether the bill's sponsor is in the majority
party. To test the effect of changes to bills after their introduction on our
ability to predict their final outcome, we compared using the bill text and meta
data available at the time of introduction with using the most recent data. At
the time of introduction context-only predictions outperform text-only, and with
the newest data text-only outperforms context-only. Combining text and context
always performs best. We conducted a global sensitivity analysis on the combined
model to determine important variables predicting enactment.
PMID- 28489869
TI - Interaction between birds and macrofauna within food webs of six intertidal
habitats of the Wadden Sea.
AB - The determination of food web structures using Ecological Network Analysis (ENA)
is a helpful tool to get insight into complex ecosystem processes. The intertidal
area of the Wadden Sea is structured into diverse habitat types which differ in
their ecological functioning. In the present study, six different intertidal
habitats (i.e. cockle field, razor clam field, mud flat, mussel bank, sand flat
and seagrass meadow) were analyzed using ENA to determine similarities and
characteristic differences in the food web structure of the systems. All six
systems were well balanced between their degree of organization and their
robustness. However, they differed in their detailed features. The cockle field
and the mussel bank exhibited a strong dependency on external imports. The razor
clam field appeared to be a rather small system with low energy transfer. In the
mud flat microphytobenthos was used as a main food source and the system appeared
to be sensitive to perturbations. Bird predation was the most pronounced in the
sand flat and the seagrass meadow and led to an increase in energy transfer and
parallel trophic cycles in these habitats. Habitat diversity appears to be an
important trait for the Wadden Sea as each subsystem seems to have a specific
role in the overall functioning of the entire ecosystem.
PMID- 28489870
TI - New gSSR and EST-SSR markers reveal high genetic diversity in the invasive plant
Ambrosia artemisiifolia L. and can be transferred to other invasive Ambrosia
species.
AB - Ambrosia artemisiifolia L., (common ragweed), is an annual invasive and highly
troublesome plant species originating from North America that has become
widespread across Europe. New sets of genomic and expressed sequence tag (EST)
based simple sequence repeats (SSRs) markers were developed in this species using
three approaches. After validation, 13 genomic SSRs and 13 EST-SSRs were retained
and used to characterize the genetic diversity and population genetic structure
of Ambrosia artemisiifolia populations from the native (North America) and
invasive (Europe) ranges of the species. Analysing the mating system based on
maternal families did not reveal any departure from complete allogamy and excess
homozygosity was mostly due the presence of null alleles. High genetic diversity
and patterns of genetic structure in Europe suggest two main introduction events
followed by secondary colonization events. Cross-species transferability of the
newly developed markers to other invasive species of the Ambrosia genus was
assessed. Sixty-five percent and 75% of markers, respectively, were transferable
from A. artemisiifolia to Ambrosia psilostachya and Ambrosia tenuifolia. 40% were
transferable to Ambrosia trifida, this latter species being seemingly more
phylogenetically distantly related to A. artemisiifolia than the former two.
PMID- 28489871
TI - Anatomy, taphonomy, and phylogenetic implications of a new specimen of Eolambia
caroljonesa (Dinosauria: Ornithopoda) from the Cedar Mountain Formation, Utah,
USA.
AB - BACKGROUND: Eolambia caroljonesa is the most abundant dinosaur in the lower
Cenomanian Mussentuchit Member of the Cedar Mountain Formation of Utah, and one
of the most completely known non-hadrosaurid iguanodontians from North America.
In addition to the large holotype and paratype partial skulls, copious remains of
skeletally immature individuals, including three bonebeds, have been referred to
E. caroljonesa. Nevertheless, aspects of the postcranial anatomy of this taxon,
particularly the pelvic girdle, have remained ambiguous due to the lack of
associated postcranial material of larger, more mature individuals.
METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a recently discovered associated
partial postcranial skeleton of a large Eolambia caroljonesa. This specimen, FMNH
PR 3847, provides new anatomical data regarding the vertebral column and pelvic
girdle, supplementing previous diagnoses and descriptions of E. caroljonesa. A
new phylogenetic analysis incorporating information from FMNH PR 3847 places E.
caroljonesa as a basal hadrosauromorph closely related to Protohadros byrdi from
the Cenomanian Woodbine Formation of Texas. Histological analysis of FMNH PR 3847
reveals that it represents a subadult individual eight to nine years of age.
Taphonomic analysis indicates that FMNH PR 3847 was preserved in a crevasse splay
deposit, along with an unusual abundance of small crocodylomorph material.
CONCLUSIONS/SIGNIFICANCE: FMNH PR 3847 provides a wealth of new morphological
data, adding to the anatomical and systematic characterization of Eolambia
caroljonesa, and histological data, revealing new information on growth history
in a basal hadrosauromorph. Taphonomic characterization of FMNH PR 3847 and
associated vertebrate material will allow comparison with other vertebrate
localities in the Mussentuchit Member of the Cedar Mountain Formation.
PMID- 28489872
TI - Gender differences in scientific collaborations: Women are more egalitarian than
men.
AB - By analyzing a unique dataset of more than 270,000 scientists, we discovered
substantial gender differences in scientific collaborations. While men are more
likely to collaborate with other men, women are more egalitarian. This is
consistently observed over all fields and regardless of the number of
collaborators a scientist has. The only exception is observed in the field of
engineering, where this gender bias disappears with increasing number of
collaborators. We also found that the distribution of the number of collaborators
follows a truncated power law with a cut-off that is gender dependent and related
to the gender differences in the number of published papers. Considering
interdisciplinary research, our analysis shows that men and women behave
similarly across fields, except in the case of natural sciences, where women with
many collaborators are more likely to have collaborators from other fields.
PMID- 28489873
TI - Identification of persistent benthic assemblages in areas with different
temperature variability patterns through broad-scale mapping.
AB - Ecosystem-based management is a place-based approach that considers the
relationships between system parts. Due to the complexity of ecosystems in the
marine environment it is often difficult to define these relationships in space
and time. Maps illustrate spatial concepts. Here we promote ecosystem-based
spatial thinking by layering datasets from a larger project that mapped benthic
fauna, substrate characteristics, and oceanic conditions on monthly, annual and
decadal time scales along the U.S. continental shelf. By combining maps of
persistent benthic megafauna and bottom temperature variability over
approximately 90,000 km2, we identified wide spread benthic animal assemblages
and regional disparity in temperature variability. From a broad-scale perspective
the locations of the assemblage appear to be related to sea scallop population
dynamics and indicate potential regional differences in climate change
resiliency. These findings offer information on a scale that correlates with
marine spatial planning, and could be used as a starting point for further
investigation. To spur additional analysis and facilitate their linkage to other
datasets, these datasets are available through public, online data portals.
Overall, this study demonstrates how the growth of maps from single to multiple
elements can help promote and facilitate the multifactor, ecosystem-based
thinking needed to support regional ocean planning.
PMID- 28489874
TI - Tafazzin (TAZ) promotes the tumorigenicity of cervical cancer cells and inhibits
apoptosis.
AB - Tafazzin (TAZ) is often aberrantly expressed in some cancers, including rectal
cancer and thyroid neoplasms. However, the function of TAZ in cervical cancer
cells remains unknown. This study aims to explore the expression and function of
TAZ in cervical cancer cells. Here, we determined the expression of TAZ protein
in normal cervical tissue (NC, n = 27), high-grade squamous intraepithelial
lesions (HSIL, n = 26) and squamous cervical carcinoma (SCC, n = 41) by
immunohistochemistry, the expression of TAZ protein gradually increased from NC
to HSIL to SCC. TAZ was overexpressed or down-regulated in cervical cancer cells
by stably transfecting a TAZ-expressing plasmid or a shRNA plasmid targeting TAZ.
In vitro, the cell growth curves and MTT assays showed that TAZ may promote the
growth and viability of cervical cancer cells. In vivo, xenografts experiment
showed that TAZ may increase tumor-forming ability. The percentage of apoptosis
cells analyzed by FACS and TUNEL assays consistently showed that TAZ inhibits
apoptosis in cervical cancer cells. Furthermore, the Cleaved Caspase 9 and
Cleaved Caspase 3 were down-regulated by TAZ in cervical cancer cells. Taken
together, this study demonstrated that TAZ is overexpressed in cervical cancer
and may promote tumorigenicity of cervical cancer cells and inhibit apoptosis.
PMID- 28489875
TI - Functional data analysis of sleeping energy expenditure.
AB - Adequate sleep is crucial during childhood for metabolic health, and physical and
cognitive development. Inadequate sleep can disrupt metabolic homeostasis and
alter sleeping energy expenditure (SEE). Functional data analysis methods were
applied to SEE data to elucidate the population structure of SEE and to
discriminate SEE between obese and non-obese children. Minute-by-minute SEE in
109 children, ages 5-18, was measured in room respiration calorimeters. A
smoothing spline method was applied to the calorimetric data to extract the true
smoothing function for each subject. Functional principal component analysis was
used to capture the important modes of variation of the functional data and to
identify differences in SEE patterns. Combinations of functional principal
component analysis and classifier algorithm were used to classify SEE. Smoothing
effectively removed instrumentation noise inherent in the room calorimeter data,
providing more accurate data for analysis of the dynamics of SEE. SEE exhibited
declining but subtly undulating patterns throughout the night. Mean SEE was
markedly higher in obese than non-obese children, as expected due to their
greater body mass. SEE was higher among the obese than non-obese children
(p<0.01); however, the weight-adjusted mean SEE was not statistically different
(p>0.1, after post hoc testing). Functional principal component scores for the
first two components explained 77.8% of the variance in SEE and also differed
between groups (p = 0.037). Logistic regression, support vector machine or random
forest classification methods were able to distinguish weight-adjusted SEE
between obese and non-obese participants with good classification rates (62-64%).
Our results implicate other factors, yet to be uncovered, that affect the weight
adjusted SEE of obese and non-obese children. Functional data analysis revealed
differences in the structure of SEE between obese and non-obese children that may
contribute to disruption of metabolic homeostasis.
PMID- 28489876
TI - Socioeconomic inequalities in mortality, morbidity and diabetes management for
adults with type 1 diabetes: A systematic review.
AB - AIMS: To systematically review the evidence of socioeconomic inequalities for
adults with type 1 diabetes in relation to mortality, morbidity and diabetes
management. METHODS: We carried out a systematic search across six relevant
databases and included all studies reporting associations between socioeconomic
indicators and mortality, morbidity, or diabetes management for adults with type
1 diabetes. Data extraction and quality assessment was undertaken for all
included studies. A narrative synthesis was conducted. RESULTS: A total of 33
studies were identified. Twelve cohort, 19 cross sectional and 2 case control
studies met the inclusion criteria. Regardless of healthcare system, low
socioeconomic status was associated with poorer outcomes. Following adjustments
for other risk factors, socioeconomic status was a statistically significant
independent predictor of mortality in 9/10 studies and morbidity in 8/10 studies
for adults with type 1 diabetes. There appeared to be an association between low
socioeconomic status and some aspects of diabetes management. Although only 3 of
16 studies made adjustments for confounders and other risk factors, poor diabetes
management was associated with lower socioeconomic status in 3/3 of these
studies. CONCLUSIONS: Low socioeconomic status is associated with higher levels
of mortality and morbidity for adults with type 1 diabetes even amongst those
with access to a universal healthcare system. The association between low
socioeconomic status and diabetes management requires further research given the
paucity of evidence and the potential for diabetes management to mitigate the
adverse effects of low socioeconomic status.
PMID- 28489877
TI - Low back pain in healthy postmenopausal women and the effect of physical
activity: A secondary analysis in a randomized trial.
AB - Epidemiological studies on the prevalence of musculoskeletal pain have
consistently shown that this is a relevant health problem, with non-specific low
back pain (LBP) being the most commonly reported in adult females. Conflicting
data on the association between LBP symptoms and physical activity (PA) have been
reported. Here, we investigated the prevalence of LBP and the effect of a 24
month non-specific PA intervention on changes in LBP prevalence in a series of
Italian healthy postmenopausal women. We performed a secondary analysis in the
frame of the DAMA trial, a factorial randomized intervention trial aimed to
evaluate the ability of a 24-month intervention, based on moderate-intensity PA,
and/or dietary modification, in reducing mammographic breast density in healthy
postmenopausal women. The PA intervention included at least 1 hour/day of
moderate PA and a more strenuous weekly activity, collective walks and
theoretical group sessions. A self-administered pain questionnaire was
administered at baseline and at the end of the intervention. The questionnaire
was specifically structured to investigate the occurrence of musculoskeletal
pain, the body localization, intensity and duration of the pain. Two hundred and
ten women (102 randomized to PA intervention, 108 not receiving the PA
intervention) filled out the questionnaires. At baseline LBP was present in 32.9%
of the participants. Among women randomized to the PA intervention, LBP
prevalence at follow up (21.6%) was lower than at baseline (33.3%) (p = 0.02),
while in women who did not receive the PA intervention the LBP prevalence at
baseline and follow up were 32.4% and 25.9%, respectively (p = 0.30). Overall,
there was no significant between-group effect of PA intervention on LBP. Further
studies are needed to understand the role of non-specific PA intervention, aimed
to improve overall fitness, on LBP prevalence.
PMID- 28489878
TI - Impact of life history traits on gene flow: A multispecies systematic review
across oceanographic barriers in the Mediterranean Sea.
AB - BACKGROUND: Marine species can demonstrate strong genetic differentiation and
population structure despite the hypothesis of open seas and high connectivity.
Some suggested drivers causing the genetic breaks are oceanographic barriers and
the species' biology. We assessed the relevance of seven major oceanographic
fronts on species connectivity while considering their dispersal capacity and
life strategy. METHODS: We systematically reviewed the scientific articles
reporting population genetic differentiation along the Mediterranean Sea and
across the Atlantic-Mediterranean transition. We retained those considering at
least one sampling locality at each side of an oceanographic front, and at least
two localities with no-front between them to correctly assess the effect of the
front. To estimate the impact of life history characteristics affecting
connectivity we considered the planktonic larval duration (PLD) and adult life
strategy. RESULTS: Oceanographic barriers in the Mediterranean Sea seem to reduce
gene flow globally; however, this effect is not homogeneous considering the life
history traits of the species. The effect of the oceanographic fronts reduces
gene flow in highly mobile species with PLD larger than 2-4 weeks. Benthic
sessile species and/or with short PLD (< 2 weeks) have more significant genetic
breaks between localities than species with higher motility; however, genetic
differentiation occurs independently of the presence of a front. CONCLUSION:
Genetic connectivity is important for populations to recover from anthropogenic
or natural impacts. We show that species with low mobility, mostly habitat
formers, have high genetic differentiation but low gene flow reduction mediated
by the front, therefore, considering the importance of these species, we
emphasize the vulnerability of the Mediterranean ecosystems and the necessity of
protection strategies based on the whole ecosystem.
PMID- 28489880
TI - Carbon storage in the seagrass meadows of Gazi Bay, Kenya.
AB - Vegetated marine habitats are globally important carbon sinks, making a
significant contribution towards mitigating climate change, and they provide a
wide range of other ecosystem services. However, large gaps in knowledge remain,
particularly for seagrass meadows in Africa. The present study estimated biomass
and sediment organic carbon (Corg) stocks of four dominant seagrass species in
Gazi Bay, Kenya. It compared sediment Corg between seagrass areas in vegetated
and un-vegetated 'controls', using the naturally patchy occurence of seagrass at
this site to test the impacts of seagrass growth on sediment Corg. It also
explored relationships between the sediment and above-ground Corg, as well as
between the total biomass and above-ground parameters. Sediment Corg was
significantly different between species, range: 160.7-233.8 Mg C ha-1 (compared
to the global range of 115.3 to 829.2 Mg C ha-1). Vegetated areas in all species
had significantly higher sediment Corg compared with un-vegetated controls; the
presence of seagrass increased Corg by 4-6 times. Biomass carbon differed
significantly between species with means ranging between 4.8-7.1 Mg C ha-1
compared to the global range of 2.5-7.3 Mg C ha-1. To our knowledge, these are
among the first results on seagrass sediment Corg to be reported from African
seagrass beds; and contribute towards our understanding of the role of seagrass
in global carbon dynamics.
PMID- 28489879
TI - Lack of significant associations with early career performance suggest no link
between the DMRT3 "Gait Keeper" mutation and precocity in Coldblooded trotters.
AB - The Swedish-Norwegian Coldblooded trotter (CBT) is a local breed in Sweden and
Norway mainly used for harness racing. Previous studies have shown that a
mutation from cytosine (C) to adenine (A) in the doublesex and mab-3 related
transcription factor 3 (DMRT3) gene has a major impact on harness racing
performance of different breeds. An association of the DMRT3 mutation with early
career performance has also been suggested. The aim of the current study was to
investigate this proposed association in a randomly selected group of CBTs. 769
CBTs (485 raced, 284 unraced) were genotyped for the DMRT3 mutation. The
association with racing performance was investigated for 13 performance traits
and three different age intervals: 3 years, 3 to 6 years, and 7 to 10 years of
age, using the statistical software R. Each performance trait was analyzed for
association with DMRT3 using linear models. The results suggest no association of
the DMRT3 mutation with precocity (i.e. performance at 3 years of age). Only two
traits (race time and number of disqualifications) were significantly different
between the genotypes, with AA horses having the fastest times and CC horses
having the highest number of disqualifications at 3 years of age. The frequency
of the AA genotype was significantly lower in the raced CBT sample compared with
the unraced sample and less than 50% of the AA horses participated in a race. For
the age intervals 3 to 6 and 7 to 10 years the AA horses also failed to
demonstrate significantly better performance than the other genotypes. Although
suggested as the most favorable genotype for racing performance in Standardbreds
and Finnhorses across all ages, the AA genotype does not appear to be associated
with superior performance, early or late, in the racing career of CBTs.
PMID- 28489881
TI - Hypoxia-activated prodrug TH-302 decreased survival rate of canine lymphoma cells
under hypoxic condition.
AB - We tested the hypotheses that hypoxic stimulation enhances growth potentials of
canine lymphoma cells by activating hypoxia-inducible factor 1alpha (HIF-1alpha),
and that the hypoxia-activated prodrug (TH-302) inhibits growth potentials in the
cells. We investigated how hypoxic culture affects the growth rate,
chemoresistance, and invasiveness of canine lymphoma cells and doxorubicin (DOX)
resistant lymphoma cells, and influences of TH-302 on survival rate of the cells
under hypoxic conditions. Our results demonstrated that hypoxic culture
upregulated the expression of HIF-1alpha and its target genes, including ATP
binding cassette transporter B1 (ABCB1), ATP-binding cassette transporter G2
(ABCG2), platelet-derived growth factor (PDGF), vascular endothelial growth
factor (VEGF), and survivin, and enhanced the growth rate, DOX resistance, and
invasiveness of the cells. Additionally, TH-302 decreased the survival rate of
the cells under hypoxic condition. Our studies suggest that hypoxic stimulation
may advance the tumorigenicity of canine lymphoma cells, favoring malignant
transformation. Therefore, the data presented may contribute to the development
of TH-302-based hypoxia-targeting therapies for canine lymphoma.
PMID- 28489882
TI - Preparation of a novel antiserum to aromatase with high affinity and specificity:
Its clinicopathological significance on breast cancer tissue.
AB - Aromatase inhibitors have been widely used for the endocrine treatment of
estrogen-dependent breast cancer in postmenopausal patients. However,
clinicopathological studies of aromatase have been limited due to unsatisfactory
specificity and/or restricted availability of anti-aromatase antibodies. Here, we
have generated a polyclonal antiserum with high affinity and specificity for
human aromatase using a monoclonal antibody tagged immunoaffinity chromatography
on an industrial production scale. Our preliminary immunohistochemical analysis
of 221 invasive breast cancer cases indicated that 87.3% (193/221) had at least
5% aromatase positive cells. The histoscore for aromatase was inversely
correlated with pT (p = 0.019), pN (p = 0.001), stage (p < 0.001), histologic
grade (p = 0.003), lymphatic infiltration (p < 0.001), venous infiltration (p <
0.001), and Ki-67 index (p < 0.001). However, cancer aromatase expression was
independent of estrogen receptor (ER), progesterone receptor (PgR), and human
epidermal growth factor receptor 2 statuses. This antiserum will be applicable to
clinicopathological examination of aromatase in addition to ER and PgR for an
appropriate use of aromatase inhibitor on the treatment of breast cancer. Further
studies on the relationship between Aromatase inhibitors have been widely used
for the endocrine treatment of estrogen-dependent breast cancer in postmenopausal
patients. However, clinicopathological studies of aromatase have been limited due
to unsatisfactory specificity and/or restricted availability of anti-aromatase
antibodies. Here, we have generated a polyclonal antiserum with high affinity and
specificity for human aromatase using a monoclonal antibody tagged immunoaffinity
chromatography on an industrial production scale. Our preliminary
immunohistochemical analysis of 221 invasive breast cancer cases indicated that
87.3% (193/221) had at least 5% aromatase positive cells. The histoscore for
aromatase was inversely correlated with pT (p = 0.019), pN (p = 0.001), stage (p
< 0.001), histologic grade (p = 0.003), lymphatic infiltration (p < 0.001),
venous infiltration (p < 0.001), and Ki-67 index (p < 0.001). However, cancer
aromatase expression was independent of estrogen receptor (ER), progesterone
receptor (PgR), and human epidermal growth factor receptor 2 statuses. This
antiserum will be applicable to clinicopathological examination of aromatase in
addition to ER and PgR for an appropriate use of aromatase inhibitor on the
treatment of breast cancer. Further studies on the relationship between aromatase
expression and aromatase inhibitors are warranted.
PMID- 28489884
TI - Comparison of the prognostic values of preoperative inflammation-based parameters
in patients with breast cancer.
AB - Peripheral blood-derived inflammation-based markers, including C-reactive protein
(CRP), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR),
and platelet-to-lymphocyte ratio (PLR) are indicators of prognosis in various
malignant tumors. The present study aimed to identify the inflammation-based
parameters that are most suitable for predicting outcomes in patients with breast
cancer. Two hundred ninety-six patients who underwent surgery for localized
breast cancer were reviewed retrospectively. The association between
clinicopathological factors and inflammation-based parameters were investigated.
Univariate and multivariate Cox regression analyses were performed to identify
independent prognostic indicators associated with disease-free survival (DFS).
The NLR level correlated significantly with tumor size (P<0.05). The PLR level
correlated with the expression of estrogen receptor and lymph node involvement
(P<0.05). Univariate analysis revealed that lower CRP and PLR values as well as
tumor size, lymph node involvement, and nuclear grade were significantly
associated with superior DFS (CRP: P<0.01; PLR, tumor size, lymph node
involvement, and nuclear grade: P<0.05). On multivariate analysis, CRP (hazard
ratio [HR]: 2.85, 95% confidence interval [CI]: 1.03-7.88, P<0.05), PLR (HR:
2.61, 95% CI: 1.07-6.36, P<0.05) and nuclear grade (HR: 3.066, 95% CI: 1.26-7.49,
P<0.05) were significant prognostic indicators of DFS in patients with breast
cancer. Neither LMR nor NLR significantly predicted DFS. Both preoperative CRP
and PLR values were independently associated with poor prognosis in patients with
breast carcinoma; these were superior to other inflammation-based scores in terms
of prognostic ability.
PMID- 28489883
TI - BMP-7 induces apoptosis in human germinal center B cells and is influenced by TGF
beta receptor type I ALK5.
AB - Selection and maturation of B cells into plasma cells producing high-affinity
antibodies occur in germinal centers (GC). GCs form transiently in secondary
lymphoid organs upon antigen challenge, and the GC reaction is a highly regulated
process. TGF-beta is a potent negative regulator, but the influence of other
family members including bone morphogenetic proteins (BMPs) is less known.
Studies of human peripheral blood B lymphocytes showed that BMP-6 suppressed
plasmablast differentiation, whereas BMP-7 induced apoptosis. Here, we show that
human naive and GC B cells had a strikingly different receptor expression
pattern. GC B cells expressed high levels of BMP type I receptor but low levels
of type II receptors, whereas naive B cells had the opposite pattern.
Furthermore, GC B cells had elevated levels of downstream signaling components
SMAD1 and SMAD5, but reduced levels of the inhibitory SMAD7. Functional assays of
GC B cells revealed that BMP-7 suppressed the viability-promoting effect of CD40L
and IL-21, but had no effect on CD40L- and IL-21-induced differentiation into
plasmablasts. BMP-7-induced apoptosis was counteracted by a selective TGF-beta
type I receptor (ALK4/5/7) inhibitor, but not by a selective BMP receptor type I
inhibitor. Furthermore, overexpression of truncated ALK5 in a B-cell line
counteracted BMP-7-induced apoptosis, whereas overexpression of truncated ALK4
had no effect. BMP-7 mRNA and protein was readily detected in tonsillar B cells,
indicating a physiological relevance of the study. Altogether, we identified BMP
7 as a negative regulator of GC B-cell survival. The effect was counteracted by
truncated ALK5, suggesting greater complexity in regulating BMP-7 signaling than
previously believed.
PMID- 28489885
TI - Visit-to-visit glycemic variability is a strong predictor of chronic obstructive
pulmonary disease in patients with type 2 diabetes mellitus: Competing risk
analysis using a national cohort from the Taiwan diabetes study.
AB - BACKGROUND: This study aims to examine the association between visit-to-visit
glucose variability, which was measured by coefficient of variation (CV) of
fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c), and risk of chronic
obstructive pulmonary disease (COPD) in a large number of patients with type 2
diabetes with an average follow-up of 7.58 years. METHODS: We conducted a
retrospective cohort study on 27,257 patients with type 2 diabetes who
participated in the National Diabetes Case Management Program in Taiwan. Visit-to
visit variability in HbA1c and FPG at baseline and the incidence of COPD were
analyzed using a modified Cox proportional hazards model considering competing
risks. RESULTS: A total of 2,346 incident cases of COPD. Patients were grouped
into tertiles of FPG-CV and HbA1c-CV. The incidence rates in the first, second,
and third tertiles were 9.87, 11.06, and 13.19, respectively, for FPG-CV and
10.2, 11.81, and 12.07, for HbA1c-CV per 1000 person-years. After adjusting for
age, gender, diabetes duration, treatment type, smoking, hypertension,
hyperlipidemia, baseline FPG and HbA1c levels, and complications, both FPG-CV and
HbA1c-CV were independently associated with COPD. The hazard ratios of COPD for
the third terile compared with the first tertile of FPG-CV were 1.26 (95%
confidence interval [CI]: 1.13-1.40). Moreover, the hazard ratios of COPD for the
third and second tertiles compared with the first tertile of HbA1c-CV were 1.13
(1.02-1.25) and 1.13 (1.02-1.26), respectively. CONCLUSIONS: Patients with FPG-CV
higher than 34.6% or HbA1c-CV higher than 8.4% exhibited an increased risk of
COPD. This finding confirmed the linear relationship of FPG-CV and HbA1c-CV to
COPD. Visit-to-visit variability in FPG and HbA1c levels are strong predictors of
COPD in patients with type 2 diabetes. Future studies should focus on lung
dysfunction in diabetes, and adequate glucose control strategy in regular
clinical practices must be established for COPD prevention.
PMID- 28489886
TI - Bystander activation of irrelevant CD4+ T cells following antigen-specific
vaccination occurs in the presence and absence of adjuvant.
AB - Autoimmune and other chronic inflammatory diseases (AID) are prevalent diseases
which can severely impact the quality of life of those that suffer from the
disease. In most cases, the etiology of these conditions have remained unclear.
Immune responses that take place e.g. during natural infection or after
vaccination are often linked with the development or exacerbation of AID. It is
highly debated if vaccines induce or aggravate AID and in particular adjuvants
are mentioned as potential cause. Since vaccines are given on a large scale to
healthy individuals but also to elderly and immunocompromised individuals, more
research is warranted. Non-specific induction of naive or memory autoreactive T
cells via bystander activation is one of the proposed mechanisms of how
vaccination might be involved in AID. During bystander activation, T cells
unrelated to the antigen presented can be activated without (strong) T cell
receptor (TCR) ligation, but via signals derived from the ongoing response
directed against the vaccine-antigen or adjuvant at hand. In this study we have
set up a TCR transgenic T cell transfer mouse model by which we were able to
measure local bystander activation of transferred and labeled CD4+ T cells.
Intramuscular injection with the highly immunogenic Complete Freund's Adjuvant
(CFA) led to local in vivo proliferation and activation of intravenously
transferred CD4+ T cells in the iliac lymph node. This local bystander activation
was also observed after CFA prime and Incomplete Freund's Adjuvant (IFA) boost
injection. Furthermore, we showed that an antigen specific response is sufficient
for the induction of a bystander activation response and the general, immune
stimulating effect of CFA or IFA does not appear to increase this effect. In
other words, no evidence was obtained that adjuvation of antigen specific
responses is essential for bystander activation.
PMID- 28489887
TI - Regorafenib inhibited gastric cancer cells growth and invasion via CXCR4
activated Wnt pathway.
AB - AIM: Regorafenib is an oral small-molecule multi kinase inhibitor. Recently,
several clinical trials have revealed that regorafenib has an anti-tumor activity
in gastric cancer. However, only part of patients benefit from regorafenib, and
the mechanisms of regorafenib's anti-tumor effect need further demonstrating. In
this study, we would assess the potential anti-tumor effects and the underlying
mechanisms of regorafenib in gastric cancer cells, and explore novel biomarkers
for patients selecting of regorafenib. METHODS: The anti-tumor effects of
regorafenib on gastric cancer cells were analyzed via cell proliferation and
invasion. The underlying mechanisms were demonstrated using molecular biology
techniques. RESULTS: We found that regorafenib inhibited cell proliferation and
invasion at the concentration of 20MUmol/L and in a dose dependent manner. The
anti-tumor effects of regorafenib related to the decreased expression of CXCR4,
and elevated expression and activation of CXCR4 could reverse the inhibition
effect of regorafenib on gastric cancer cells. Further studies revealed that
regorafenib reduced the transcriptional activity of Wnt/beta-Catenin pathway and
led to decreased expression of Wnt pathway target genes, while overexpression and
activation of CXCR4 could attenuate the inhibition effect of regorafenib on
Wnt/beta-Catenin pathway. CONCLUSIONS: Our findings demonstrated that regorafenib
effectively inhibited cell proliferation and invasion of gastric cancer cells via
decreasing the expression of CXCR4 and further reducing the transcriptional
activity of Wnt/beta-Catenin pathway.
PMID- 28489888
TI - A two-question tool to assess the risk of repeated falls in the elderly.
AB - INTRODUCTION: Older adults' perception of their own risk of fall has never been
included into screening tools. The goal of this study was to evaluate the
predictive validity of questions on subjects' self-perception of their own risk
of fall. METHODS: This prospective study was conducted on a probabilistic sample
of 772 Spanish community-dwelling older adults, who were followed-up for a one
year period. At a baseline visit, subjects were asked about their recent history
of falls (question 1: "Have you fallen in the last 6 months?"), as well as on
their perception of their own risk of fall by using two questions (question 2:
"Do you think you may fall in the next few months?" possible answers: yes/no;
question 3: "What is the probability that you fall in the next few months?"
possible answers: low/intermediate/high). The follow-up consisted of quarterly
telephone calls, where the number of falls occurred in that period was recorded.
RESULTS: A short questionnaire built with questions 1 and 3 showed 70%
sensitivity (95% CI: 56%-84%), 72% specificity (95% CI: 68%-76%) and 0.74 area
under the ROC curve (95% CI: 0.66-0.82) for prediction of repeated falls in the
subsequent year. CONCLUSIONS: The estimation of one's own risk of fall has
predictive validity for the occurrence of repeated falls in older adults. A short
questionnaire including a question on perception of one's own risk of fall and a
question on the recent history of falls had good predictive validity.
PMID- 28489889
TI - An environmental assessment and risk map of Ascaris lumbricoides and Necator
americanus distributions in Manufahi District, Timor-Leste.
AB - BACKGROUND: In Timor-Leste there have been intermittent and ineffective soil
transmitted helminth (STH) deworming programs since 2004. In a resource
constrained setting, having information on the geographic distribution of STH can
aid in prioritising high risk communities for intervention. This study aimed to
quantify the environmental risk factors for STH infection and to produce a risk
map of STH in Manufahi district, Timor-Leste. METHODOLOGY/PRINCIPAL FINDINGS:
Georeferenced cross-sectional data and stool samples were obtained from 2,194
participants in 606 households in 24 villages in the Manufahi District as part of
cross sectional surveys done in the context of the "WASH for Worms" randomised
controlled trial. Infection status was determined for Ascaris lumbricoides and
Necator americanus using real-time quantitative polymerase chain reaction.
Baseline infection data were linked to environmental data obtained for each
household. Univariable and multivariable multilevel mixed-effects logistic
regression analysis with random effects at the village and household level were
conducted, with all models adjusted for age and sex. For A. lumbricoides, being a
school-aged child increased the odds of infection, whilst higher temperatures in
the coolest quarter of the year, alkaline soils, clay loam/loam soils and woody
savannas around households were associated with decreased infection odds. For N.
americanus, greater precipitation in the driest month, higher average enhanced
vegetation index, age and sandy loam soils increased infection odds, whereas
being female and living at higher elevations decreased the odds of infection.
Predictive risk maps generated for Manufahi based upon these final models
highlight the high predicted risk of N. americanus infection across the district
and the more focal nature of A. lumbricoides infection. The predicted risk of any
STH infection is high across the entire district. CONCLUSIONS/SIGNIFICANCE: The
widespread predicted risk of any STH infection in 6 to 18 year olds provides
strong evidence to support strategies for control across the entire geographical
area. As few studies include soil texture and pH in their analysis, this study
adds to a growing body of evidence suggesting these factors influence STH
infection distribution. This study also further supports that A. lumbricoides
prefers acidic soils, highlighting a potential relatively unexplored avenue for
control. TRIAL REGISTRATION: ClinicalTrials.gov ACTRN12614000680662.
PMID- 28489890
TI - Unmasking inequalities: Sub-national maternal and child mortality data from two
urban slums in Lagos, Nigeria tells the story.
AB - INTRODUCTION: Nigeria has one of the highest maternal mortality ratios in the
world as well as high perinatal mortality. Unfortunately, the country does not
have the resources to assess this critical indicator with the conventional health
information system and measuring its progress toward the goal of ending
preventable maternal deaths is almost impossible. Medecins Sans Frontieres (MSF)
conducted a cross-sectional study to assess maternal and perinatal mortality in
Makoko Riverine and Badia East, two of the most vulnerable slums of Lagos.
MATERIALS AND METHODS: The study was a cross-sectional, community-based household
survey. Nearly 4,000 households were surveyed. The sisterhood method was utilized
to estimate maternal mortality and the preceding births technique was used to
estimate newborn and child mortality. Questions regarding health seeking behavior
were posed to female interviewees and self-reported data were collected. RESULTS:
Data was collected from 3963 respondents for a total of 7018 sisters ever
married. The maternal mortality ratio was calculated at 1,050/100,000 live births
(95% CI: 894-1215), and the lifetime risk of maternal death at 1:18. The neonatal
mortality rate was extracted from 1967 pregnancies reported and was estimated at
28.4/1,000; infant mortality at 43.8/1,000 and under-five mortality at 103/1,000.
Living in Badia, giving birth at home and belonging to the Egun ethnic group were
associated with higher perinatal mortality. Half of the last pregnancies were
reportedly delivered in private health facilities. Proximity to home was the main
influencing factor (32.4%) associated with delivery at the health facility.
DISCUSSION: The maternal mortality ratio found in these urban slum populations
within Lagos is extremely high, compared to the figure estimated for Lagos State
of 545 per 100,000 live births. Urgent attention is required to address these
neglected and vulnerable neighborhoods. Efforts should be invested in obtaining
data from poor, marginalized, and hard-to-reach populations in order to identify
pockets of marginalization needing additional resources and tailored approaches
to guarantee equitable treatment and timely access to quality health services for
vulnerable groups. This study demonstrates the importance of sub-regional,
disaggregated data to identify and redress inequities that exist among poor,
remote, vulnerable populations-as in the urban slums of Lagos.
PMID- 28489891
TI - RNA-seq approach to analysis of gene expression profiles in dark green islands
and light green tissues of Cucumber mosaic virus-infected Nicotiana tabacum.
AB - Dark green islands (DGIs) surrounded by light green tissues (LGTs) are common
leaf symptoms of plants that are systemically infected by various viruses that
induce leaf mosaic in infected plants. The inoculation of Cucumber mosaic virus
(CMV) in Nicotiana tabacum produced a commonly occurring sequence of classic
patterns of DGIs and LGTs. Previous studies confirmed that there are significant
differences between DGIs and LGTs in terms of physiology, biochemistry and
molecular biology, but the mechanisms by which DGIs form remain unclear. To
investigate the global gene expression changes that occur in these special
tissues, individual differential gene expression tag libraries were constructed
from three total RNA samples isolated from DGIs, LGTs and control plants (CK) and
were sequenced using an Illumina HiSeqTM 2000. An analysis of differentially
expressed genes (DEGs) and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and
Genomes (KEGG) pathway enrichment analysis were performed. These analyses
revealed the differences between DGIs, LGTs and CK. GO enrichment and KEGG
pathway analyses suggested that several pathways related to photosynthesis and
chlorophyll metabolism were enriched in DGIs compared to LGTs and CK. Several
pathways related to apoptosis were significantly up-regulated in LGTs compared to
DGIs. Additionally, we identified sets of DEGs that may be related to the
formation or development of DGIs and LGTs. Our systematic analyses provide
comprehensive transcriptomic information regarding DGIs and LGTs in CMV-infected
N. tabacum. These data will help characterize the detailed mechanisms of DGI and
LGT formation.
PMID- 28489893
TI - Correction: Novel decay dynamics revealed for virus-mediated drug activation in
cytomegalovirus infection.
AB - [This corrects the article DOI: 10.1371/journal.ppat.1006299.].
PMID- 28489892
TI - Exposure to maternal obesogenic diet worsens some but not all pre-cancer
phenotypes in a murine genetic model of prostate cancer.
AB - Prostate cancer research has been predominantly focused on adult exposures and
risk factors. However, because the prostate develops during gestation and early
life, exposure to external factors, such as obesity, during development could
affect the prostate cancer progression in adults. Our previous work demonstrated
that exposure to a high fat/high sugar (HF/HS) diet during gestation and until
weaning stimulated prostate hyperplasia and altered the Pten/Akt pathway in adult
mice fed a normal diet after weaning. Here, we asked whether maternal exposure to
HF/HS would worsen prostate phenotypes in mice lacking Pten, a widely accepted
driver of prostate cancer. We found that, at six weeks of age, both Chow
(control)-and HF/HS-exposed Pten knockout mice showed evidence of murine PIN that
included ducts with central comedo necrosis but that the HF/HS exposure did not
influence murine PIN progression. The Pten knockout mice exposed to HF/HS in
utero had significantly more mitotic cells than Pten knockouts exposed to Chow
diet. In the Pten null background, the maternal HF/HS diet enhanced proliferation
but did not have an additive effect on Akt activation. We observed neuroendocrine
differentiation in Pten knockout mice, a phenotype that had not been previously
described in this model.
PMID- 28489895
TI - Flowering after disaster: Early Danian buckthorn (Rhamnaceae) flowers and leaves
from Patagonia.
AB - Southern-Hemisphere terrestrial communities from the early Paleocene are poorly
known, but recent work on Danian plant fossils from the Salamanca Formation in
Chubut Province, Argentina are providing critical data on earliest Paleocene
floras. The fossils described here come from a site in the Salamanca Formation
dating to ca. 1 million years or less after the end-Cretaceous extinction event;
they are the first fossil flowers reported from the Danian of South America, and
possible the entire Southern Hemisphere. They are compressions and impressions in
flat-laminated light gray shale, and they belong to the family Rhamnaceae
(buckthorns). Flowers of Notiantha grandensis gen. et sp. nov. are pentamerous,
with distinctly keeled calyx lobes projecting from the hypanthium, clawed and
cucullate emarginate petals, antepetalous stamens, and a pentagonal floral disk
that fills the hypanthium. Their phylogenetic position was evaluated using a
molecular scaffold approach combined with morphological data. Results indicate
that the flowers are most like those of extant ziziphoid Rhamnaceae. The
associated leaves, assigned to Suessenia grandensis gen. et sp. nov. are simple
and ovate, with serrate margins and three acrodromous basal veins. They conform
to the distinctive leaves of some extant Rhamnaceae in the ziziphoid and
ampelozizyphoid clades. These fossils provide the first unequivocal megafossil
evidence of Rhamnaceae in the Southern Hemisphere, demonstrating that Rhamnaceae
expanded beyond the tropics by the earliest Paleocene. Given previous reports of
rhamnaceous pollen in the late Paleogene and Neogene of Antarctica and southern
Australia, this new occurrence increases the possibility of high-latitude
dispersal of this family between South America and Australia via Antarctica
during the Cenozoic.
PMID- 28489894
TI - Analysis of global DNA methylation changes in primary human fibroblasts in the
early phase following X-ray irradiation.
AB - Epigenetic alterations may contribute to the generation of cancer cells in a
multi-step process of tumorigenesis following irradiation of normal body cells.
Primary human fibroblasts with intact cell cycle checkpoints were used as a model
to test whether X-ray irradiation with 2 and 4 Gray induces direct epigenetic
effects (within the first cell cycle) in the exposed cells. ELISA-based
fluorometric assays were consistent with slightly reduced global DNA methylation
and hydroxymethylation, however the observed between-group differences were
usually not significant. Similarly, bisulfite pyrosequencing of interspersed LINE
1 repeats and centromeric alpha-satellite DNA did not detect significant
methylation differences between irradiated and non-irradiated cultures.
Methylation of interspersed ALU repeats appeared to be slightly increased (one
percentage point; p = 0.01) at 6 h after irradiation with 4 Gy. Single-cell
analysis showed comparable variations in repeat methylation among individual
cells in both irradiated and control cultures. Radiation-induced changes in
global repeat methylation, if any, were much smaller than methylation variation
between different fibroblast strains. Interestingly, alpha-satellite DNA
methylation positively correlated with gestational age. Finally, 450K methylation
arrays mainly targeting genes and CpG islands were used for global DNA
methylation analysis. There were no detectable methylation differences in genic
(promoter, 5' UTR, first exon, gene body, 3' UTR) and intergenic regions between
irradiated and control fibroblast cultures. Although we cannot exclude minor
effects, i.e. on individual CpG sites, collectively our data suggest that global
DNA methylation remains rather stable in irradiated normal body cells in the
early phase of DNA damage response.
PMID- 28489896
TI - Short-term activity cycles impede information transmission in ant colonies.
AB - Rhythmical activity patterns are ubiquitous in nature. We study an oscillatory
biological system: collective activity cycles in ant colonies. Ant colonies have
become model systems for research on biological networks because the interactions
between the component parts are visible to the naked eye, and because the time
ordered contact network formed by these interactions serves as the substrate for
the distribution of information and other resources throughout the colony. To
understand how the collective activity cycles influence the contact network
transport properties, we used an automated tracking system to record the movement
of all the individuals within nine different ant colonies. From these
trajectories we extracted over two million ant-to-ant interactions. Time-series
analysis of the temporal fluctuations of the overall colony interaction and
movement rates revealed that both the period and amplitude of the activity cycles
exhibit a diurnal cycle, in which daytime cycles are faster and of greater
amplitude than night cycles. Using epidemiology-derived models of transmission
over networks, we compared the transmission properties of the observed periodic
contact networks with those of synthetic aperiodic networks. These simulations
revealed that contrary to some predictions, regularly-oscillating contact
networks should impede information transmission. Further, we provide a
mechanistic explanation for this effect, and present evidence in support of it.
PMID- 28489897
TI - Analysis of statistical and standard algorithms for detecting muscle onset with
surface electromyography.
AB - The timing of muscle activity is a commonly applied analytic method to understand
how the nervous system controls movement. This study systematically evaluates six
classes of standard and statistical algorithms to determine muscle onset in both
experimental surface electromyography (EMG) and simulated EMG with a known onset
time. Eighteen participants had EMG collected from the biceps brachii and vastus
lateralis while performing a biceps curl or knee extension, respectively. Three
established methods and three statistical methods for EMG onset were evaluated.
Linear envelope, Teager-Kaiser energy operator + linear envelope and sample
entropy were the established methods evaluated while general time series
mean/variance, sequential and batch processing of parametric and nonparametric
tools, and Bayesian changepoint analysis were the statistical techniques used.
Visual EMG onset (experimental data) and objective EMG onset (simulated data)
were compared with algorithmic EMG onset via root mean square error and linear
regression models for stepwise elimination of inferior algorithms. The top
algorithms for both data types were analyzed for their mean agreement with the
gold standard onset and evaluation of 95% confidence intervals. The top
algorithms were all Bayesian changepoint analysis iterations where the parameter
of the prior (p0) was zero. The best performing Bayesian algorithms were p0 = 0
and a posterior probability for onset determination at 60-90%. While existing
algorithms performed reasonably, the Bayesian changepoint analysis methodology
provides greater reliability and accuracy when determining the singular onset of
EMG activity in a time series. Further research is needed to determine if this
class of algorithms perform equally well when the time series has multiple bursts
of muscle activity.
PMID- 28489899
TI - Development of an immunochromatographic strip test for the rapid detection of
zearalenone in wheat from Jiangsu province, China.
AB - A colloidal gold (ICS) test was developed for rapid detection of zearalenone
(ZEN) in wheat samples. The mAb against ZEN was prepared in our laboratory and
labelled with colloidal gold as a probe for the ICS test. The conditions were
optimized and 30 nm colloidal gold nanoparticles were chosen for optimal
performance. Millipore 135 was chosen as the NC membrane for its level of
sensitivity. The optimum amount of coated antigen ZEN-OVA and anti-ZEN mAb was
0.5 mg/mL and 8 MUg/mL, respectively. The ICS test, which has a detection limit
of 15 ng/mL for ZEN, could be completed in 5 min. Analysis of ZEN in 202 wheat
samples over three consecutive years revealed that data obtained from the ICS
test were in a good agreement with LC-MS/MS data. This result demonstrated that
the ICS test could be used as a qualitative tool to screen on-site for ZEN.
PMID- 28489898
TI - Comparative genomic study of ALDH gene superfamily in Gossypium: A focus on
Gossypium hirsutum under salt stress.
AB - Aldehyde dehydrogenases (ALDHs) are a superfamily of enzymes which play important
role in the scavenging of active aldehydes molecules. In present work, a
comprehensive whole-genomic study of ALDH gene superfamily was carried out for an
allotetraploid cultivated cotton species, G. hirsutum, as well as in parallel
relative to their diploid progenitors, G. arboreum and G. raimondii. Totally, 30
and 58 ALDH gene sequences belong to 10 families were identified from diploid and
allotetraploid cotton species, respectively. The gene structures among the
members from same families were highly conserved. Whole-genome duplication and
segmental duplication might be the major driver for the expansion of ALDH gene
superfamily in G. hirsutum. In addition, the expression patterns of GhALDH genes
were diverse across tissues. Most GhALDH genes were induced or repressed by salt
stress in upland cotton. Our observation shed lights on the molecular
evolutionary properties of ALDH genes in diploid cottons and their
alloallotetraploid derivatives. It may be useful to mine key genes for
improvement of cotton response to salt stress.
PMID- 28489900
TI - Scanning double-sided documents without incurring show-through by learning to
fuse two complementary images using multilayer perceptron.
AB - This paper presents a novel method for scanning duplex-printed documents without
incurring the unwanted show-through artifact. The proposed method achieves the
goal of eliminating the leaked-out reverse-side content by fusing a white backed
scan image with a black backed scan image of the document. The fusion is
accomplished using a multilayer perceptron having learned a fusion mapping from
manually corrected document images. The main novel contributions of this work
include (1) being the first to propose to accomplish the goal of show through
free scanning by fusing a white backed scan image with a black backed scan image
of the document; (2) proposing a learning approach using a multilayer perceptron
to learn the fusion mapping from manually corrected scan images; and (3)
proposing to use the pixel value histogram of reverse-side-printed area as well
as the pixel value histogram of duplex-printed area to quantitatively indicate
show through severity to facilitate objective comparison of the methods in
consideration. The experiment results show that the proposed method is remarkably
more powerful in eliminating show through than the two state-of-the-art methods
in comparison.
PMID- 28489901
TI - Characterization and proteomic profile of extracellular vesicles from peritoneal
dialysis efflux.
AB - Peritoneal Dialysis (PD) is considered the best option for a cost-effective mid
term dialysis in patients with Chronic Renal Failure. However, functional failure
of the peritoneal membrane (PM) force many patients to stop PD treatment and
start haemodialysis. Currently, PM functionality is monitored by the peritoneal
equilibration test, a tedious technique that often show changes when the membrane
damage is advanced. As in other pathologies, the identification and
characterization of extracellular vesicles (EVs) in the peritoneal dialysis
efflux (PDE) may represent a non-invasive alternative to identify biomarkers of
membrane failure. Using size-exclusion chromatography, we isolated EVs from PDE
in a group of patients. Vesicles were characterized by the presence of
tetraspanin markers, nanoparticle tracking analysis profile, cryo-electron
microscopy and mass spectrometry. Here, we report the isolation and
characterization of PDE-EVs. Based on mass spectrometry, we have found a set of
well-conserved proteins among patients. Interestingly, the peptide profile also
revealed remarkable changes between newly enrolled and longer-treated PD
patients. These results are the first step to the identification of PDE-EVs based
new markers of PM damage, which could support clinicians in their decision-making
in a non-invasive manner.
PMID- 28489902
TI - Disturbance of a rare seabird by ship-based tourism in a marine protected area.
AB - Managers of marine protected areas (MPAs) must often seek ways to allow for
visitation while minimizing impacts to the resources they are intended to
protect. Using shipboard observers, we quantified the "zone of disturbance" for
Kittlitz's and marbled murrelets (Brachyramphus brevirostris and B. marmoratus)
exposed to large cruise ships traveling through Glacier Bay National Park, one of
the largest MPAs in North America. In the upper reaches of Glacier Bay, where
Kittlitz's murrelets predominated, binary logistic regression models predicted
that 61% of all murrelets within 850 m perpendicular distance of a cruise ship
were disturbed (defined as flushing or diving), whereas in the lower reaches,
where marbled murrelets predominated, this percentage increased to 72%. Using
survival analysis, murrelets in both reaches were found to react at greater
distances when ships approached indirectly, presumably because of the ship's
larger profile, suggesting murrelets responded to visual rather than audio cues.
No management-relevant covariates (e.g., ship velocity, route distance from
shore) were found to be important predictors of disturbance, as distance from
ship to murrelet accounted for > 90% of the explained variation in murrelet
response. Utilizing previously published murrelet density estimates from Glacier
Bay, and applying an average empirical disturbance probability (68%) out to 850 m
from a cruise ship's typical route, we estimated that a minimum of 9.8-19.6% of
all murrelets in Glacier Bay are disturbed per ship entry. Whether these
disturbance levels are inconsistent with Park management objectives, which
include conserving wildlife as well as providing opportunities for visitation,
depends in large part on whether disturbance events caused by cruise ships have
impacts on murrelet fitness, which remains uncertain.
PMID- 28489903
TI - Atoll-scale patterns in coral reef community structure: Human signatures on
Ulithi Atoll, Micronesia.
AB - The dynamic relationship between reefs and the people who utilize them at a
subsistence level is poorly understood. This paper characterizes atoll-scale
patterns in shallow coral reef habitat and fish community structure, and
correlates these with environmental characteristics and anthropogenic factors,
critical to conservation efforts for the reefs and the people who depend on them.
Hierarchical clustering analyses by site for benthic composition and fish
community resulted in the same 3 major clusters: cluster 1-oceanic (close
proximity to deep water) and uninhabited (low human impact); cluster 2-oceanic
and inhabited (high human impact); and cluster 3-lagoonal (facing the inside of
the lagoon) and inhabited (highest human impact). Distance from village, reef
exposure to deep water and human population size had the greatest effect in
predicting the fish and benthic community structure. Our study demonstrates a
strong association between benthic and fish community structure and human use
across the Ulithi Atoll (Yap State, Federated States of Micronesia) and confirms
a pattern observed by local people that an 'opportunistic' scleractinian coral
(Montipora sp.) is associated with more highly impacted reefs. Our findings
suggest that small human populations (subsistence fishing) can nevertheless have
considerable ecological impacts on reefs due, in part, to changes in fishing
practices rather than overfishing per se, as well as larger global trends.
Findings from this work can assist in building local capacity to manage reef
resources across an atoll-wide scale, and illustrates the importance of
anthropogenic impact even in small communities.
PMID- 28489904
TI - Underreporting of high-risk water and sanitation practices undermines progress on
global targets.
AB - Water and sanitation indicators under the Millennium Development Goals failed to
capture high-risk practices undertaken on a regular basis. In conjunction with
local partners, fourteen rounds of household surveys using mobile phones with a
customized open-source application were conducted across nine study geographies
in Asia and Africa. In addition to the main water and sanitation facilities,
interviewees (n = 245,054) identified all water and sanitation options regularly
used for at least one season of the year. Unimproved water consumption and open
defecation were targeted as high-risk practices. We defined underreporting as the
difference between the regular and main use of high-risk practices. Our estimates
of high-risk practices as the main option matched the widely accepted Demographic
and Health Surveys (DHS) estimates within the 95% confidence interval. However,
estimates of these practices as a regular option was far higher than the DHS
estimates. Across the nine geographies, median underreporting of unimproved water
use was 5.5%, with a range of 0.5% to 13.9%. Median underreporting of open
defecation was much higher at 9.9%, with a range of 2.7% to 11.5%. This resulted
in an underreported population of 25 million regularly consuming unimproved water
and 50 million regularly practicing open defecation. Further examination of data
from Ethiopia suggested that location and socio-economic factors were significant
drivers of underreporting. Current global monitoring relies on a framework that
considers the availability and use of a single option to meet drinking water and
sanitation needs. Our analysis demonstrates the use of multiple options and
widespread underreporting of high-risk practices. Policies based on current
monitoring data, therefore, fail to consider the range of challenges and
solutions to meeting water and sanitation needs, and result in an inflated sense
of progress. Mobile surveys offer a cost-effective and innovative platform to
rapidly and repeatedly monitor critical development metrics.
PMID- 28489905
TI - An investigation of modelling and design for software service applications.
AB - Software services offer the opportunity to use a component-based approach for the
design of applications. However, this needs a deeper understanding of how to
develop service-based applications in a systematic manner, and of the set of
properties that need to be included in the 'design model'. We have used a
realistic application to explore systematically how service-based designs can be
created and described. We first identified the key properties of an SOA (service
oriented architecture) and then undertook a single-case case study to explore its
use in the development of a design for a large-scale application in energy
engineering, modelling this with existing notations wherever possible. We
evaluated the resulting design model using two walkthroughs with both domain and
application experts. We were able to successfully develop a design model around
the ten properties identified, and to describe it by adapting existing design
notations. A component-based approach to designing such systems does appear to be
feasible. However, it needs the assistance of a more integrated set of notations
for describing the resulting design model.
PMID- 28489906
TI - Neocortical activity is stimulus- and scale-invariant.
AB - Mounting evidence supports the hypothesis that the cortex operates near a
critical state, defined as the transition point between order (large-scale
activity) and disorder (small-scale activity). This criticality is manifested by
power law distribution of the size and duration of spontaneous cascades of
activity, which are referred as neuronal avalanches. The existence of such
neuronal avalanches has been confirmed by several studies both in vitro and in
vivo, among different species and across multiple spatial scales. However,
despite the prevalence of scale free activity, still very little is known
concerning whether and how the scale-free nature of cortical activity is altered
during external stimulation. To address this question, we performed in vivo two
photon population calcium imaging of layer 2/3 neurons in primary visual cortex
of behaving mice during visual stimulation and conducted statistical analyses on
the inferred spike trains. Our investigation for each mouse and condition
revealed power law distributed neuronal avalanches, and irregular spiking
individual neurons. Importantly, both the avalanche and the spike train
properties remained largely unchanged for different stimuli, while the cross
correlation structure varied with stimuli. Our results establish that
microcircuits in the visual cortex operate near the critical regime, while
rearranging functional connectivity in response to varying sensory inputs.
PMID- 28489908
TI - Sexual dimorphism in African elephant social rumbles.
AB - This study used the source and filter theory approach to analyse sex differences
in the acoustic features of African elephant (Loxodonta africana) low-frequency
rumbles produced in social contexts ('social rumbles'). Permuted discriminant
function analysis revealed that rumbles contain sufficient acoustic information
to predict the sex of a vocalizing individual. Features primarily related to the
vocalizer's size, i.e. fundamental frequency variables and vocal tract resonant
frequencies, differed significantly between the sexes. Yet, controlling for age
and size effects, our results indicate that the pronounced sexual size dimorphism
in African elephants is partly, but not exclusively, responsible for sexual
differences in social rumbles. This provides a scientific foundation for future
work investigating the perceptual and functional relevance of specific acoustic
characteristics in African elephant vocal sexual communication.
PMID- 28489909
TI - Correction: Buzz Factor or Innovation Potential: What Explains Cryptocurrencies'
Returns?
AB - [This corrects the article DOI: 10.1371/journal.pone.0169556.].
PMID- 28489907
TI - Anti-oxidative effects of 4-hydroxybenzyl alcohol in astrocytes confer protective
effects in autocrine and paracrine manners.
AB - 4-Hydroxybenzyl alcohol (4-HBA) is an important phenolic constituent of Gastrodia
elata Blume (GEB), a traditional herbal medicine used in East Asia. Many
activities have been reported to underlie the beneficial effects of 4-HBA in the
brain, and in particular, its anti-inflammatory, anti-oxidative, and anti-zinc
toxic effects have been implicated in the postischemic brain. Here, the authors
investigated the anti-oxidative effect of 4-HBA on astrocytes and sought to
identify the underlying molecular mechanisms involved. 4-HBA dose-dependently
suppressed H2O2-induced astrocyte cell death. More specifically, pre-incubation
of C6 cells (an astrocyte cell line) with 100 MUM 4-HBA for 6 hrs increased
survival when cells were treated with H2O2 (100 MUM, 1 hr) from 54.2+/-0.7% to
85.9+/-1.5%. In addition, 4-HBA was found to up-regulate and activate Nrf2, and
subsequently, to induce the expressions of several anti-oxidative genes, such as,
HO-1, NQO1, and GCLM. Notably, HO-1 was induced by 3.4-fold in 4-HBA-treated C6
cells, and siRNA-mediated HO-1 knockdown demonstrated that Nrf2 activation and HO
1 induction were responsible for the observed cytoprotective effect of 4-HBA. ERK
and Akt signaling pathways were activated by 4-HBA in C6 cells, suggesting their
involvements in protective effect of 4-HBA. In addition, 4-HBA-conditioned
astrocyte culture medium was found to have neuroprotective effects on primary
neuronal cultures or fresh C6 cells exposed to oxidative stress, and these
effects seemed to be mediated by glial cell line-derived neurotrophic factor
(GDNF) and vascular endothelial growth factor (VEGF), which both accumulated in 4
HBA-treated astrocyte culture media. Thus, the 4-HBA-mediated activation of Nrf2
and induction of HO-1 in astrocytes were found to act via autocrine and paracrine
mechanisms to confer protective effects. Furthermore, given the pleiotropic
effects of 4-HBA with respect to its targeting of various brain cell types and
functions, it would appear that 4-HBA has therapeutic potential for the
prevention and amelioration of various brain diseases.
PMID- 28489910
TI - Random domain name and address mutation (RDAM) for thwarting reconnaissance
attacks.
AB - Network address shuffling is a novel moving target defense (MTD) that invalidates
the address information collected by the attacker by dynamically changing or
remapping the host's network addresses. However, most network address shuffling
methods are limited by the limited address space and rely on the host's static
domain name to map to its dynamic address; therefore these methods cannot
effectively defend against random scanning attacks, and cannot defend against an
attacker who knows the target's domain name. In this paper, we propose a network
defense method based on random domain name and address mutation (RDAM), which
increases the scanning space of the attacker through a dynamic domain name method
and reduces the probability that a host will be hit by an attacker scanning IP
addresses using the domain name system (DNS) query list and the time window
methods. Theoretical analysis and experimental results show that RDAM can defend
against scanning attacks and worm propagation more effectively than general
network address shuffling methods, while introducing an acceptable operational
overhead.
PMID- 28489911
TI - Human beta-defensin-2 production upon viral and bacterial co-infection is
attenuated in COPD.
AB - Viral-bacterial co-infections are associated with severe exacerbations of COPD.
Epithelial antimicrobial peptides, including human beta-defensin-2 (HBD-2), are
integral to innate host defenses. In this study, we examined how co-infection of
airway epithelial cells with rhinovirus and Pseudomonas aeruginosa modulates HBD
2 expression, and whether these responses are attenuated by cigarette smoke and
in epithelial cells obtained by bronchial brushings from smokers with normal lung
function or from COPD patients. When human airway epithelial cells from normal
lungs were infected with rhinovirus, Pseudomonas aeruginosa, or the combination,
co-infection with rhinovirus and bacteria resulted in synergistic induction of
HBD-2 (p<0.05). The combination of virus and flagellin replicated this
synergistic increase (p<0.05), and synergy was not seen using a flagella
deficient mutant Pseudomonas (p<0.05). The effects of Pseudomonas aeruginosa were
mediated via interactions of flagellin with TLR5. The effects of HRV-16 depended
upon viral replication but did not appear to be mediated via the intracellular
RNA helicases, retinoic acid-inducible gene-I or melanoma differentiation
associated gene-5. Cigarette smoke extract significantly decreased HBD-2
production in response to co-infection. Attenuated production was also observed
following co-infection of cells obtained from healthy smokers or COPD patients
compared to healthy controls (p<0.05). We conclude that co-exposure to HRV-16 and
Pseudomonas aeruginosa induces synergistic production of HBD-2 from epithelial
cells and that this synergistic induction of HBD-2 is reduced in COPD patients.
This may contribute to the more severe exacerbations these patients experience in
response to viral-bacterial co-infections.
PMID- 28489912
TI - Eight habitats, 38 threats and 55 experts: Assessing ecological risk in a multi
use marine region.
AB - Identifying the relative risk human activities pose to a habitat, and the
ecosystem services they provide, can guide management prioritisation and resource
allocation. Using a combination of expert elicitation to assess the probable
effect of a threat and existing data to assess the level of threat exposure, we
conducted a risk assessment for 38 human-mediated threats to eight marine
habitats (totalling 304 threat-habitat combinations) in Spencer Gulf, Australia.
We developed a score-based survey to collate expert opinion and assess the
relative effect of each threat to each habitat, as well as a novel and
independent measure of knowledge-based uncertainty. Fifty-five experts
representing multiple sectors and institutions participated in the study, with 6
to 15 survey responses per habitat (n = 81 surveys). We identified key threats
specific to each habitat; overall, climate change threats received the highest
risk rankings, with nutrient discharge identified as a key local-scale stressor.
Invasive species and most fishing-related threats, which are commonly identified
as major threats to the marine environment, were ranked as low-tier threats to
Spencer Gulf, emphasising the importance of regionally-relevant assessments.
Further, we identified critical knowledge gaps and quantified uncertainty scores
for each risk. Our approach will facilitate prioritisation of resource allocation
in a region of increasing social, economic and environmental importance, and can
be applied to marine regions where empirical data are lacking.
PMID- 28489913
TI - Human perception of electrical stimulation on the surface of somatosensory
cortex.
AB - Recent advancement in electrocorticography (ECoG)-based brain-computer interface
technology has sparked a new interest in providing somatosensory feedback using
ECoG electrodes, i.e., cortical surface electrodes. We conducted a 28-day study
of cortical surface stimulation in an individual with arm paralysis due to
brachial plexus injury to examine the sensation produced by electrical
stimulation of the somatosensory cortex. A high-density ECoG grid was implanted
over the somatosensory and motor cortices. Stimulation through cortical surface
electrodes over the somatosensory cortex successfully elicited arm and hand
sensations in our participant with chronic paralysis. There were three key
findings. First, the intensity of perceived sensation increased monotonically
with both pulse amplitude and pulse frequency. Second, changing pulse width
changed the type of sensation based on qualitative description provided by the
human participant. Third, the participant could distinguish between stimulation
applied to two neighboring cortical surface electrodes, 4.5 mm center-to-center
distance, for three out of seven electrode pairs tested. Taken together, we found
that it was possible to modulate sensation intensity, sensation type, and evoke
sensations across a range of locations from the fingers to the upper arm using
different stimulation electrodes even in an individual with chronic impairment of
somatosensory function. These three features are essential to provide effective
somatosensory feedback for neuroprosthetic applications.
PMID- 28489915
TI - An 8.5 m long ammonite drag mark from the Upper Jurassic Solnhofen Lithographic
Limestones, Germany.
AB - Trackways and tracemakers preserved together in the fossil record are rare.
However, the co-occurrence of a drag mark, together with the dead animal that
produced it, is exceptional. Here, we describe an 8.5 m long ammonite drag mark
complete with the preserved ammonite shell (Subplanites rueppellianus) at its
end. Previously recorded examples preserve ammonites with drag marks of < 1 m.
The specimen was recovered from a quarry near Solnhofen, southern Germany. The
drag mark consists of continuous parallel ridges and furrows produced by the ribs
of the ammonite shell as it drifted just above the sediment surface, and does not
reflect behaviour of the living animal.
PMID- 28489914
TI - miR-27a and miR-449b polymorphisms associated with a risk of idiopathic recurrent
pregnancy loss.
AB - OBJECTIVE: MicroRNAs (miRNAs) regulate gene expression during the peri
implantation period. The purpose of this study was to investigate whether genetic
polymorphisms in the four miRNAs associated with fetal or placental development
play roles in the development of idiopathic recurrent pregnancy loss (RPL) in
Korean females. STUDY DESIGN: A case-control study involving 225 controls and 387
women with at least two consecutively recurrent pregnancy losses between 1999 and
2012 was performed. The genotypes of the four miRNA polymorphisms, including miR
27a rs895819, miR-423 rs6505162, miR-449b rs10061133, and miR-605 rs2043556, were
analyzed by the polymerase chain reaction-restriction fragment length
polymorphism assay. Odds ratios and 95% confidence intervals were estimated using
multivariate analyses after maternal age adjustments. The relationships between
each of the four microRNA genotypes and each of the six clinical parameters of
the RPL patients (plasma homocysteine and folate levels, natural killer cell
number, platelet count, prothrombin time, and, activated partial thromboplastin
time) were analyzed using multiple linear regression analyses. RESULTS: Our
results suggest that weak associations between decreased RPL risk and the
genotypes of miR-27a (AG and AG+GG), combination genotype of miR-27a/miR-423
(AG/GC), and haplotypes of miR-27a/miR-423/miR-449b/miR-605 (G-C-A-G) and miR
27a/miR-449b/miR-605 (G-A-G), whereas weak associations between increased RPL
risk and genotypes of miR-449b (GG and AG+GG), combination genotypes of miR
423/miR-449b (CC/GG and CA/AG), miR-449b/miR-605 (AG/AG), haplotypes of miR
27a/miR-423/miR-449b/miR-605 (A-C-G-A, A-A-A-G, and G-C-G-G), miR-27a/miR-423/miR
449b (A-C-G), miR-27a/miR-449b/miR-605 (A-A-G, A-G-A, and G-G-G), miR-423/miR
449b/miR-605 (C-G-G and A-A-G), and miR-423/miR-449b (C-G and A-A). The genotypes
of miR-27a (AG and AG+GG) also showed significant contributions to the prediction
of folate levels in RPL patients. CONCLUSIONS: The study showed associations
between miRNA polymorphisms (miR-27a rs895819 and miR-449b rs10061133) and RPL
development, and between the miRNA polymorphism (miR-27a rs895819) and plasma
folate levels.
PMID- 28489917
TI - Mucosal fluid glycoprotein DMBT1 suppresses twitching motility and virulence of
the opportunistic pathogen Pseudomonas aeruginosa.
AB - It is generally thought that mucosal fluids protect underlying epithelial
surfaces against opportunistic infection via their antimicrobial activity.
However, our published data show that human tear fluid can protect against the
major opportunistic pathogen Pseudomonas aeruginosa independently of
bacteriostatic activity. Here, we explored the mechanisms for tear protection,
focusing on impacts of tear fluid on bacterial virulence factor expression.
Results showed that tear fluid suppressed twitching motility, a type of surface
associated movement conferred by pili. Previously, we showed that twitching is
critical for P. aeruginosa traversal of corneal epithelia, exit from epithelial
cells after internalization, and corneal virulence. Inhibition of twitching by
tear fluid was dose-dependent with dilutions to 6.25% retaining activity.
Purified lactoferrin, lysozyme, and contrived tears containing these, and many
other, tear components lacked the activity. Systematic protein fractionation,
mass spectrometry, and immunoprecipitation identified the glycoprotein DMBT1
(Deleted in Malignant Brain Tumors 1) in tear fluid as required. DMBT1 purified
from human saliva also inhibited twitching, as well as P. aeruginosa traversal of
human corneal epithelial cells in vitro, and reduced disease pathology in a
murine model of corneal infection. DMBT1 did not affect PilA expression, nor
bacterial intracellular cyclicAMP levels, and suppressed twitching motility of P.
aeruginosa chemotaxis mutants (chpB, pilK), and an adenylate cyclase mutant
(cyaB). However, dot-immunoblot assays showed purified DMBT1 binding of pili
extracted from PAO1 suggesting that twitching inhibition may involve a direct
interaction with pili. The latter could affect extension or retraction of pili,
their interactions with biotic or abiotic surfaces, or cause their aggregation.
Together, the data suggest that DMBT1 inhibition of twitching motility
contributes to the mechanisms by which mucosal fluids protect against P.
aeruginosa infection. This study also advances our understanding of how mucosal
fluids protect against infection, and suggests directions for novel biocompatible
strategies to protect our surface epithelia against a major opportunistic
pathogen.
PMID- 28489918
TI - OCT-angiography: A qualitative and quantitative comparison of 4 OCT-A devices.
AB - PURPOSE: To compare the quality of four OCT-angiography(OCT-A) modules. METHOD:
The retina of nineteen healthy volunteers were scanned with four OCT-devices
(Topcon DRI-OCT Triton Swept-source OCT, Optovue RTVue-XR, a prototype Spectralis
OCT2, Heidelberg-Engineering and Zeiss Cirrus 5000-HD-OCT). The device-software
generated en-face OCT-A images of the superficial (SCP) and deep capillary
plexuses (DCP) were evaluated and scored by 3 independent retinal imaging
experts. The SCP vessel density was assessed using Angiotool-software. After the
inter-grader reliability assessment, a consensus grading was performed and the
modules were ranked based on their scoring. RESULTS: There was no significant
difference in the vessel density among the modules (Zeiss 48.7+/-4%, Optovue
47.9+/-3%, Topcon 48.3+/-2%, Heidelberg 46.5+/-4%, p = 0.2). The numbers of
discernible vessel-bifurcations differed significantly on each module (Zeiss 2+/
0.9 bifurcations, Optovue 2.5+/-1.2, Topcon 1.3+/-0.7 and Heidelberg 0.5+/-0.6,
p<=0.001). The ranking of each module differed depending on the evaluated
parameter. In the overall ranking, the Zeiss module was superior and in 90%
better than the median (Bonferroni corrected p-value = 0.04). Optovue was better
than the median in 60%, Topcon in 40% and Heidelberg module in 10%, however these
differences were not statistically significant. CONCLUSION: Each of the four
evaluated OCT-A modules had particular strengths, which differentiated it from
their competitors.
PMID- 28489916
TI - Generational distribution of a Candida glabrata population: Resilient old cells
prevail, while younger cells dominate in the vulnerable host.
AB - Similar to other yeasts, the human pathogen Candida glabrata ages when it
undergoes asymmetric, finite cell divisions, which determines its replicative
lifespan. We sought to investigate if and how aging changes resilience of C.
glabrata populations in the host environment. Our data demonstrate that old C.
glabrata are more resistant to hydrogen peroxide and neutrophil killing, whereas
young cells adhere better to epithelial cell layers. Consequently, virulence of
old compared to younger C. glabrata cells is enhanced in the Galleria mellonella
infection model. Electron microscopy images of old C. glabrata cells indicate a
marked increase in cell wall thickness. Comparison of transcriptomes of old and
young C. glabrata cells reveals differential regulation of ergosterol and Hog
pathway associated genes as well as adhesion proteins, and suggests that aging is
accompanied by remodeling of the fungal cell wall. Biochemical analysis supports
this conclusion as older cells exhibit a qualitatively different lipid
composition, leading to the observed increased emergence of fluconazole
resistance when grown in the presence of fluconazole selection pressure. Older C.
glabrata cells accumulate during murine and human infection, which is
statistically unlikely without very strong selection. Therefore, we tested the
hypothesis that neutrophils constitute the predominant selection pressure in
vivo. When we altered experimentally the selection pressure by antibody-mediated
removal of neutrophils, we observed a significantly younger pathogen population
in mice. Mathematical modeling confirmed that differential selection of older
cells is sufficient to cause the observed demographic shift in the fungal
population. Hence our data support the concept that pathogenesis is affected by
the generational age distribution of the infecting C. glabrata population in a
host. We conclude that replicative aging constitutes an emerging trait, which is
selected by the host and may even play an unanticipated role in the transition
from a commensal to a pathogen state.
PMID- 28489919
TI - Efficacy and safety of gemcitabine plus docetaxel in Japanese patients with
unresectable or recurrent bone and soft tissue sarcoma: Results from a single
institutional analysis.
AB - BACKGROUND: Combination therapy with gemcitabine and docetaxel has been reported
to be a good therapeutic strategy for patients with soft tissue sarcoma. The aim
of the present study was to analyze the efficacy and toxicity of gemcitabine with
docetaxel in Japanese patients with advanced bone and soft tissue sarcoma.
PATIENTS AND METHODS: We retrospectively analyzed the effect of gemcitabine and
docetaxel therapy on overall response, progression-free survival, overall
survival, and toxicity in 42 patients with bone or soft tissue sarcoma who had
received the therapy between October 2006 and September 2015, at Tohoku
University Hospital. RESULTS: The median age was 55 years; 23 patients were men,
and 19 were women. Eight had bone sarcoma and 34 had soft tissue sarcoma. Forty
patients (95%) had previously been treated with one or more chemotherapeutic
regimens. The overall response rate was 6.9% and the disease control rate was
55%. The median progression-free survival was 2.3 months and the median overall
survival was 14.3 months. Grade 3 or more neutropenia and febrile neutropenia
were observed in 74% and 4.8% of all patients, respectively. CONCLUSION: The
response rate was lower and myelosuppression was more frequently observed than in
other previous reports. On the other hand, most of toxicities were enough
manageable. In addition, some patients had long survival with a good response.
Our study supports the notion that gemcitabine and docetaxel therapy is a good
therapeutic option for treating patients with advanced soft tissue sarcoma as
well as bone sarcoma, also in Asian populations.
PMID- 28489920
TI - A national study of the molecular epidemiology of HIV-1 in Australia 2005-2012.
AB - INTRODUCTION: Rates of new HIV-1 diagnoses are increasing in Australia, with
evidence of an increasing proportion of non-B HIV-1 subtypes reflecting a growing
impact of migration and travel. The present study aims to define HIV-1 subtype
diversity patterns and investigate possible HIV-1 transmission networks within
Australia. METHODS: The Australian Molecular Epidemiology Network (AMEN) HIV
collaborating sites in Western Australia, South Australia, Victoria, Queensland
and western Sydney (New South Wales), provided baseline HIV-1 partial pol
sequence, age and gender information for 4,873 patients who had genotypes
performed during 2005-2012. HIV-1 phylogenetic analyses utilised MEGA V6, with a
stringent classification of transmission pairs or clusters (bootstrap >=98%,
genetic distance <=1.5% from at least one other sequence in the cluster).
RESULTS: HIV-1 subtype B represented 74.5% of the 4,873 sequences (WA 59%, SA
68.4%, w-Syd 73.8%, Vic 75.6%, Qld 82.1%), with similar proportion of
transmission pairs and clusters found in the B and non-B cohorts (23% vs 24.5% of
sequences, p = 0.3). Significantly more subtype B clusters were comprised of >=3
sequences compared with non-B clusters (45.0% vs 24.0%, p = 0.021) and
significantly more subtype B pairs and clusters were male-only (88% compared to
53% CRF01_AE and 17% subtype C clusters). Factors associated with being in a
cluster of any size included; being sequenced in a more recent time period
(p<0.001), being younger (p<0.001), being male (p = 0.023) and having a B subtype
(p = 0.02). Being in a larger cluster (>3) was associated with being sequenced in
a more recent time period (p = 0.05) and being male (p = 0.008). CONCLUSION: This
nationwide HIV-1 study of 4,873 patient sequences highlights the increased
diversity of HIV-1 subtypes within the Australian epidemic, as well as
differences in transmission networks associated with these HIV-1 subtypes. These
findings provide epidemiological insights not readily available using standard
surveillance methods and can inform the development of effective public health
strategies in the current paradigm of HIV prevention in Australia.
PMID- 28489921
TI - Time trend of neurocysticercosis in children with seizures in a tertiary hospital
of western Nepal.
AB - INTRODUCTION: Neurocysticercosis is a common cause of seizure disorders in
children of Western Nepal. The clinical presentation is variable. The incidence
varies depending on the food habits and ethnicity of the population. The present
study was undertaken with the objective of studying the mode of presentation,
radiological findings and to determine the recent trend of the disease in
children of Western Nepal. METHODS: Records from the Department of Pediatrics,
Manipal Teaching Hospital, Pokhara, Nepal of children aged 0-17 years admitted
from 2003 to 2015 and with the discharge diagnosis of seizure and
neurocysticercosis (NCC) were reviewed. The diagnosis was primarily based on
clinical features, neurological involvement and CT and MRI studies. Seizures due
to other CNS pathologies were excluded. Patients with NCC were treated with
Albendazole15mg/kg/day for 28 days with supportive treatments for seizures and
raised intracranial pressure. Patients were followed up for one year after the
completion of the treatment. RESULTS: There were 1355 cases of seizure disorders,
out of which 229 (16.90%) were NCC. There were 99 (43.23%) in the age group 6-10
years followed by 91 (41.09%) in the age group of 11-15 years. Seizures were the
most common presenting symptom in 88.65%, followed by raised ICP in 9.61%.
Neuropsychiatric changes were noted in 38 cases (16.59%). CT scan findings
revealed single lesion in 78.16% and multiple lesions in 21.83%. Poisson
regression analysis showed statistically significant decline of year-wise
incidence of NCC cases (p<0.05) from 2003 to 2015. CONCLUSION: The decline in the
incidence of NCC in recent years is most probably attributed to improved hygiene
with the construction of household toilets to avoid open defecation and biannual
deworming with Albendazole as a part of School Health and Nutrition Project.
PMID- 28489922
TI - Contribution of thrombin-reactive brain pericytes to blood-brain barrier
dysfunction in an in vivo mouse model of obesity-associated diabetes and an in
vitro rat model.
AB - Diabetic complications are characterized by the dysfunction of pericytes located
around microvascular endothelial cells. The blood-brain barrier (BBB) exhibits
hyperpermeability with progression of diabetes. Therefore, brain pericytes at the
BBB may be involved in diabetic complications of the central nervous system
(CNS). We hypothesized that brain pericytes respond to increased brain thrombin
levels in diabetes, leading to BBB dysfunction and diabetic CNS complications.
Mice were fed a high-fat diet (HFD) for 2 or 8 weeks to induce obesity. Transport
of i.v.-administered sodium fluorescein and 125I-thrombin across the BBB were
measured. We evaluated brain endothelial permeability and expression of tight
junction proteins in the presence of thrombin-treated brain pericytes using a BBB
model of co-cultured rat brain endothelial cells and pericytes. Mice fed a HFD
for 8 weeks showed both increased weight gain and impaired glucose tolerance. In
parallel, the brain influx rate of sodium fluorescein was significantly greater
than that in mice fed a normal diet. HFD feeding inhibited the decline in brain
thrombin levels occurring during 6 weeks of feeding. In the HFD fed mice, plasma
thrombin levels were significantly increased, by up to 22%. 125I-thrombin was
transported across the BBB in normal mice after i.v. injection, with uptake
further enhanced by co-injection of unlabeled thrombin. Thrombin-treated brain
pericytes increased brain endothelial permeability and caused decreased
expression of zona occludens-1 (ZO-1) and occludin and morphological
disorganization of ZO-1. Thrombin also increased mRNA expression of interleukin
1beta and 6 and tumor necrosis factor-alpha in brain pericytes. Thrombin can be
transported from circulating blood through the BBB, maintaining constant levels
in the brain, where it can stimulate pericytes to induce BBB dysfunction. Thus,
the brain pericyte-thrombin interaction may play a key role in causing BBB
dysfunction in obesity-associated diabetes and represent a therapeutic target for
its CNS complications.
PMID- 28489924
TI - Neonatal and maternal outcomes of successful manual rotation to correct
malposition of the fetal head; A retrospective and prospective observational
study.
AB - OBJECTIVE: To evaluate the neonatal and maternal outcomes associated with
successful operative vaginal births assisted by manual rotation. DESIGN:
Prospective and retrospective observational study. SETTING: Delivery suite in a
tertiary referral teaching hospital in England. POPULATION: A cohort of 2,426
consecutive operative births, in the second stage of labour, complicated with
malposition of the fetal head during 2006-2013. METHODS: Outcomes of all births
successfully assisted by manual rotation followed by direct traction instruments
were compared with other methods of operative birth for fetal malposition in the
second stage of labour (rotational ventouse, Kielland forceps and caesarean
section). MAIN OUTCOME MEASURES: Associated neonatal outcomes (admission to the
special care baby unit, low cord pH, low Apgar and shoulder dystocia) and
maternal outcomes (massive obstetric haemorrhage (blood loss of >1500ml) and
obstetric anal sphincter injury). RESULTS: Births successfully assisted with
manual rotation followed by direct traction instruments, resulted in 10% (36/346)
of the babies being admitted to the Special Care Baby Unit, 4.9% (17/349)
shoulder dystocia, 2% (7/349) massive obstetric haemorrhage and 1.7% (6/349)
obstetric anal sphincter injury, similar to other methods of rotational births.
CONCLUSIONS: Adverse neonatal and maternal outcomes associated with successful
manual rotations followed by direct traction instruments were comparable to
traditional methods of operative births. There is an urgent need to standardise
the practice (guidance, training) and documentation of manual rotation followed
by direct traction instrumental deliveries that will enable assessment of its
efficacy and the absolute safety in achieving a vaginal birth.
PMID- 28489925
TI - Do the Brazilian sardine commercial landings respond to local ocean circulation?
AB - It has been reported that sea surface temperature (SST) anomalies, flow intensity
and mesoscale ocean processes, all affect sardine production, both in eastern and
western boundary current systems. Here we tested the hypothesis whether extreme
high and low commercial landings of the Brazilian sardine fisheries in the South
Brazil Bight (SBB) are sensitive to different oceanic conditions. An ocean model
(ROMS) and an individual based model (Ichthyop) were used to assess the
relationship between oceanic conditions during the spawning season and commercial
landings of the Brazilian sardine one year later. Model output was compared with
remote sensing and analysis data showing good consistency. Simulations indicate
that mortality of eggs and larvae by low temperature prior to maximum and minimum
landings are significantly higher than mortality caused by offshore advection.
However, when periods of maximum and minimum sardine landings are compared with
respect to these causes of mortality no significant differences were detected.
Results indicate that mortality caused by prevailing oceanic conditions at early
life stages alone can not be invoked to explain the observed extreme commercial
landings of the Brazilian sardine. Likely influencing factors include starvation
and predation interacting with the strategy of spawning "at the right place and
at the right time".
PMID- 28489923
TI - Differences of microparticle patterns between sickle cell anemia and hemoglobin
SC patients.
AB - Sickle cell anemia (SCA) and hemoglobin SC (HbSC) disease are the two most common
forms of sickle cell disease (SCD), a frequent hemoglobinopathy which exhibits a
highly variable clinical course. Although high levels of microparticles (MPs)
have been consistently reported in SCA and evidence of their harmful impact on
the SCA complication occurrences have been provided, no data on MP pattern in
HbSC patients has been reported so far. In this study, we determined and compared
the MP patterns of 84 HbSC and 96 SCA children, all at steady-state, using flow
cytometry. Most of circulating MPs were derived from platelets (PLTs) and red
blood cells (RBCs) in the two SCD syndromes. Moreover, we showed that HbSC
patients exhibited lower blood concentration of total MPs compared to SCA
patients, resulting mainly from a decrease of MP levels originated from RBCs and
to a lesser extent from PLTs. We did not detect any association between blood MP
concentrations and the occurrence of painful vaso-occlusive crises, acute chest
syndrome and pulmonary hypertension in both patient groups. We also demonstrated
for the first time, that whatever the considered genotype, RBC-derived MPs
exhibited higher externalized phosphatidylserine level and were larger than PLT
derived MPs.
PMID- 28489926
TI - Moving beyond pain scores: Multidimensional pain assessment is essential for
adequate pain management after surgery.
AB - BACKGROUND: Clinical experience teaches us that patients are willing to accept
postoperative pain, despite high pain intensity scores. Nevertheless,
relationships between pain scores and other methods of pain assessment, e.g.
acceptability of pain or its interference with physical functioning, are not
fully established. Our aims were to examine these relationships. METHODS: A cross
sectional study was conducted on patients who underwent major surgery between
January 2008 and August 2013. Using logistic regression, we quantified the
relationships between movement-evoked pain scores on the numerical rating scale
(NRS-MEP) and three dichotomous dependent variables: patient's opinion on
acceptability of pain (PO: acceptable or unacceptable pain); nurses' observation
of patient's performance of necessary activities to expedite recovery (NO: good
or bad performance); a compound measure judging the presence of the clinically
desirable situation of acceptable pain associated with good patients' performance
(PONO: present or not). Using Receiver Operating Characteristics (ROC) analysis,
NRS cut-off points were determined such that they best discriminate between
patients having one versus the other outcome for PO, NO and PONO. RESULTS: 15,394
assessments were obtained in 9,082 patients in the first three postoperative
days. Nine percent of the patients had unacceptable pain while having an NRS-MEP
of 0-4. An estimated 47% (95%CI = 45%-49%) of patients with an NRS-MEP of 7
described their pain as acceptable on day one. Moreover, 33% (31%-35%) performed
all required physical activities, and 22% (21%-24%) combined acceptable pain with
appropriate movement. NRS cut-off points for PO, NO and PONO were five, four and
four, respectively, but had insufficient discriminatory power. CONCLUSIONS: Our
results suggest pain management should be guided by the many dimensions of the
patient's pain experience, not solely by NRS cut-off points. Future research
should evaluate the impact of such multidimensional pain assessment on patients'
functional outcome.
PMID- 28489927
TI - Protein degradation rate is the dominant mechanism accounting for the differences
in protein abundance of basal p53 in a human breast and colorectal cancer cell
line.
AB - We determine p53 protein abundances and cell to cell variation in two human
cancer cell lines with single cell resolution, and show that the fractional width
of the distributions is the same in both cases despite a large difference in
average protein copy number. We developed a computational framework to identify
dominant mechanisms controlling the variation of protein abundance in a simple
model of gene expression from the summary statistics of single cell steady state
protein expression distributions. Our results, based on single cell data analysed
in a Bayesian framework, lends strong support to a model in which variation in
the basal p53 protein abundance may be best explained by variations in the rate
of p53 protein degradation. This is supported by measurements of the relative
average levels of mRNA which are very similar despite large variation in the
level of protein.
PMID- 28489929
TI - A content analysis of nature photographs taken by Lebanese rural youth.
AB - 'Living in Harmony with Nature' is a 2050 vision put forth by the Convention on
Biological Diversity (CBD) which takes into consideration culture and locality of
perceptions of nature and aspirations for its use. Considering that 54% of the
world population lives in cities, where nature has been decimated, the role of
rural communities, living within or in proximity of natural and semi natural
areas, will effectively influence the fate of the 'remaining' nature while they
engage in local development. Reconciling between growth and development on the
one hand, and nature conservation on the other, necessitates an understanding of
how rural communities, especially the youth, imprint their own ideas on
landscapes and develop ownership over natural spaces. In order to extend the
understanding of how harmony with nature is perceived in different parts of the
world, this paper presents the findings of primary research involving a group of
young people who live in rural areas in Lebanon, a country in the Arab Middle
East. Participatory research based on photovoice methodology was conducted with
77 young people aged 7-16 and residing in five rural villages located in
different parts of Lebanon. Photographs taken by participants indicated that for
many, nature was not perceived literally i.e. woodlands, forests, plants,
animals, etc.... Instead, the participants saw nature as part of agriculture and
local culture. Nature was also seen as symbolic expression of the participants'
inner state of mind. Narratives written to explain the photographs shed light on
the perception of harmony with nature which focused on positive family
experiences and relayed personal emotions, abstract, and holistic yet functional
view of nature. Another recurring theme that emerged from photographs and
narratives was the role of family members, in particular grandparents, as having
a strong influence on the positive perceptions of nature.
PMID- 28489928
TI - Identification and analysis of the beta-catenin1 gene in half-smooth tongue sole
(Cynoglossus semilaevis).
AB - beta-catenin is a key signalling molecule in the canonical Wnt pathway, which
plays a role in cell adhesion, embryogenesis and sex determination. However,
little is known about its function in teleosts. We cloned and characterized the
full-length beta-catenin1 gene from half-smooth tongue sole (Cynoglossus
semilaevis), which was designated CS-beta-catenin1. The CS-beta-catenin1 cDNA
consists of 2,346 nucleotides and encodes a protein with 782 amino acids.
Although CS-beta-catenin1 was transcribed in the gonads of both sexes, the level
was significantly higher in ovaries compared to testes. Furthermore, the mRNA
level of CS-beta-catenin1 was significantly upregulated at 160 days and
constantly increased until 2 years of age. In situ hybridization revealed that CS
beta-catenin1 mRNA was mainly localized in oocyte cells, especially in stage I,
II and III oocytes. When CS-beta-catenin1 expression was inhibited by injection
of quercetin in the ovaries, levels of CS-Figla and CS-foxl2 mRNA were
significantly down-regulated, and CS-dmrt1 was up-regulated, which suggested that
CS-beta-catenin1 is a potential upstream gene of CS-Figla and is involved in the
development of the ovaries, i.e., folliculogenesis.
PMID- 28489930
TI - Prognostic value of cervical nodal tumor volume in nasopharyngeal carcinoma:
Analysis of 1230 patients with positive cervical nodal metastasis.
AB - PURPOSE: To investigate the variability and prognostic value of nodal tumor
volume (NTV) in nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Data on
1230 patients with newly diagnosed stage T1-4N1-3M0 NPC treated with definitive
radiation therapy with or without chemotherapy at a single cancer center were
reviewed. NTV was determined from dose volume histogram (DVH) data. X-tile
analysis was applied to identify the optimal cut-off points for the NTV with
respect to regional recurrence-free survival (RRFS). Correlations between the TNM
classification system, NTV and RRFS were assessed using a Cox regression model.
Cross-validation based on receiver operating characteristic (ROC) curve analysis
was applied to compare the prognostic predictive validity of NTV and N
categories. RESULTS: Within a median follow-up of 49.9 (range, 1.27-76.40)
months, 61/1230 (5%) patients developed regional recurrence and 154 (12.5%)
developed distant metastasis. NTV values of 7.2 cc and 35.7 cc were identified as
the optimal cut-off points. Patients with larger NTV had poorer prognosis.
Compared with the N category, NTV was better at determining RRFS for patients
with NPC. Hazard ratios increased with NTV, ranging from 1.86 (95% confidence
interval [95% CI], 0.92-3.78) for NTV between 7.2 cc to 35.7 cc, and 3.67 (95%
CI, 1.58-8.50) for NTV > 35.7 cc. With both NTV and N category in the same Cox
regression model, only NTV remained statistically significant in the RRFS of NPC.
The validation results with ROC curves also revealed that, NTV was superior to N
category for predicting RRFS with significantly larger area under the ROC curve.
CONCLUSIONS: NTV offers important prognostic value for treatment outcomes in NPC,
especially regional control. Volumetric analysis of nodal involvement may assist
selection of patients with poor prognosis.
PMID- 28489931
TI - Cortical involvement in celiac disease before and after long-term gluten-free
diet: A Transcranial Magnetic Stimulation study.
AB - OBJECTIVE: Transcranial Magnetic Stimulation in de novo patients with Celiac
Disease previously revealed an imbalance in the excitability of cortical
facilitatory and inhibitory circuits. After a median period of 16 months of
gluten-free diet, a global increase of cortical excitability was reported,
suggesting a glutamate-mediated compensation for disease progression. We have now
evaluated cross-sectionally the changes of cortical excitability to TMS after a
much longer gluten-free diet. METHODS: Twenty patients on adequate gluten-free
diet for a mean period of 8.35 years were enrolled and compared with 20 de novo
patients and 20 healthy controls. Transcranial Magnetic Stimulation measures,
recorded from the first dorsal interosseous muscle of the dominant hand,
consisted of: resting motor threshold, cortical silent period, motor evoked
potentials, central motor conduction time, mean short-latency intracortical
inhibition and intracortical facilitation. RESULTS: The cortical silent period
was shorter in de novo patients, whereas in gluten-free diet participants it was
similar to controls. The amplitude of motor responses was significantly smaller
in all patients than in controls, regardless of the dietary regimen.
Notwithstanding the diet, all patients exhibited a statistically significant
decrease of mean short-latency intracortical inhibition and enhancement of
intracortical facilitation with respect to controls; more intracortical
facilitation in gluten-restricted compared to non-restricted patients was also
observed. Neurological examination and celiac disease-related antibodies were
negative. CONCLUSIONS: In this new investigation, the length of dietary regimen
was able to modulate the electrocortical changes in celiac disease. Nevertheless,
an intracortical synaptic dysfunction, mostly involving excitatory and inhibitory
interneurons within the motor cortex, may persist. The clinical significance of
subtle neurophysiological changes in celiac disease needs to be further
investigated.
PMID- 28489933
TI - A practical model for the train-set utilization: The case of Beijing-Tianjin
passenger dedicated line in China.
AB - As a sustainable transportation mode, high-speed railway (HSR) has become an
efficient way to meet the huge travel demand. However, due to the high
acquisition and maintenance cost, it is impossible to build enough infrastructure
and purchase enough train-sets. Great efforts are required to improve the
transport capability of HSR. The utilization efficiency of train-sets (carrying
tools of HSR) is one of the most important factors of the transport capacity of
HSR. In order to enhance the utilization efficiency of the train-sets, this paper
proposed a train-set circulation optimization model to minimize the total
connection time. An innovative two-stage approach which contains segments
generation and segments combination was designed to solve this model. In order to
verify the feasibility of the proposed approach, an experiment was carried out in
the Beijing-Tianjin passenger dedicated line, to fulfill a 174 trips train
diagram. The model results showed that compared with the traditional Ant Colony
Algorithm (ACA), the utilization efficiency of train-sets can be increased from
43.4% (ACA) to 46.9% (Two-Stage), and 1 train-set can be saved up to fulfill the
same transportation tasks. The approach proposed in the study is faster and more
stable than the traditional ones, by using which, the HSR staff can draw up the
train-sets circulation plan more quickly and the utilization efficiency of the
HSR system is also improved.
PMID- 28489932
TI - CaMKIIalpha may modulate fentanyl-induced hyperalgesia via a CeLC-PAG-RVM-spinal
cord descending facilitative pain pathway in rats.
AB - Each of the lateral capsular division of central nucleus of amygdala(CeLC),
periaqueductal gray (PAG), rostral ventromedial medulla(RVM) and spinal cord has
been proved to contribute to the development of opioid-induced hyperalgesia(OIH).
Especially, Ca2+/calmodulin-dependent protein kinase IIalpha (CaMKIIalpha) in
CeLC and spinal cord seems to play a key role in OIH modulation. However, the
pain pathway through which CaMKIIalpha modulates OIH is not clear. The pathway
from CeLC to spinal cord for this modulation was explored in the present study.
Mechanical and thermal hyperalgesia were tested by von Frey test or Hargreaves
test, respectively. CaMKIIalpha activity (phospho-CaMKIIalpha, p-CaMKIIalpha) was
evaluated by western blot analysis. CaMKIIalpha antagonist (KN93) was micro
infused into CeLC, spinal cord or PAG, respectively, to evaluate its effect on
behavioral hyperalgesia and p-CaMKIIalpha expression in CeLC, PAG, RVM and spinal
cord. Then the underlying synaptic mechanism was explored by recording miniature
excitatory postsynaptic currents (mEPSCs) on PAG slices using whole-cell voltage
clamp methods. Results showed that inhibition of CeLC, PAG or spinal CaMKIIalpha
activity respectively by KN93, reversed both mechanical and thermal hyperalgesia.
Microinjection of KN93 into CeLC decreased p-CaMKIIalpha expression in CeLC, PAG,
RVM and spinal cord; while intrathecal KN93 can only block spinal but not CeLC
CaMKIIalpha activity. KN93 injected into PAG just decreased p-CaMKIIalpha
expression in PAG, RVM and spinal cord, but not in the CeLC. Similarly, whole
cell voltage-clamp recording found the frequency and amplitude of mEPSCs in PAG
cells were decreased by KN93 added in PAG slice or micro-infused into CeLC in
vivo. These results together with previous findings suggest that CaMKIIalpha may
modulate OIH via a CeLC-PAG-RVM-spinal cord descending facilitative pain pathway.
PMID- 28489934
TI - Genetic pattern and gene localization of polydactyly in Beijing fatty chicken.
AB - Polydactyly, a common heritable limb malformation in vertebrates, is
characterized by supernumerary digits. In chickens, basic characteristics and
rough dominant genes have been explored in past decades; however, the elaborate
pattern of inheritance and the determinant gene remain obscure. In this study,
different types of polydactylism were classified by the numbers and the shapes of
toes, including the newly defined subtypes of B' and G, for the Beijing fatty
chicken, a native breed of chicken from China. Through experiments on
hybridization, we demonstrated a complete dominant inheritance of polydactyly
instead of an incomplete penetrance or genetic modification of the previous
conjecture. In particular, by using the F2 population of the five-digit purebred
line of Beijing fatty chicken backcrossed to Shiqiza chicken and by using
restriction-site associated DNA based markers, we performed a genome-wide
association study on the trait of polydactyly. Furthermore, whole genome
resequencing strategy was applied to sweep SNPs across the whole genome. An
outlier-based Fst approach was employed to search for signatures of selection,
and results indicated that the determinant mutation was found in the region
ranging from 8.3 Mb to 8.7 Mb, where the polydactyly candidate gene LMBR1 was
located. The G/T mutation of rs80659072 was identified to be highly associated
with polydactyly in our resequencing and was validated in random samples from an
expanded population. Thus, we confirmed that LMBR1 was the causative gene of
polydactyly in the Beijing fatty chicken by using GWAS with restriction-site
associated DNA based markers and resequencing.
PMID- 28489935
TI - Indoor residual spraying with micro-encapsulated pirimiphos-methyl (Actellic(r)
300CS) against malaria vectors in the Lake Victoria basin, Tanzania.
AB - BACKGROUND: The indoor residual spraying programme for malaria vectors control
was implemented in four districts of the Lake Victoria basin of Tanzania namely
Ukerewe, Sengerema, Rorya andSerengeti. Entomological monitoring activities were
implemented in one sentinel village in each district to evaluate the efficacy of
pirimiphos-methyl 300 CS sprayed on different wall surfaces and its impact
against malaria vectors post-IRS intervention. METHODS: The residual decay rate
of p-methyl 300 CS applied at a target dosage of 1g a.i./m2 on thesprayed wall
surfaces was monitored for a period of 43 weeks post-IRSusing the WHO cone wall
bioassay method. The bioassays were performed by exposing 2-5 days old unfed
susceptible female Anopheles gambiae s.s. (Kisumu strain) to sprayed wall
surfaces for a period of 30 minutes. In each sentinel village, mosquito
collection was carried out by trained community mosquito collectors. Monthly
mosquito collections were carried out from 6.00pm to 6.00am using CDC light traps
and clay pot methods for indoors host seekingand outdoors resting mosquitoes
respectively. Six traps (2 CDC light traps and 4 clay pots) were set per sentinel
village per night for28 consecutive days in a moon. PCR and ELISA were used for
mosquito species identification and sporozoite detection, respectively. RESULTS:
Based on the WHOPES recommendation, insecticides should have a minimum efficacy
of >= 80% mosquito mortality at 24 hours post exposure on the sprayed wall
surfaces to be considered effective. In this study, p-methyl 300 CS was
demonstrated to have a long residual efficacy of 21-43 weeks post-IRS on mud,
cement, painted and wood wall surfaces. Numberof anopheline mosquitoes decreased
post-IRS interventions in all sentinel villages. The highest numbers ofanopheline
mosquitoes were collected in November-December, 38-43 weeks post-IRS. A total of
270 female anopheline mosquitoes were analyzed by PCR; out of which 236 (87.4%)
were An. gambiae s.l. and 34 (12.6%) were An. funestus group. Of the 236 An.
gambiae s.l.identified 12.6% (n = 34) were An. gambiae s.s. and 68.6% (n = 162)
were An. arabiensis. Ofthe 34 An. funestus group indentified 91.2% (n = 31) were
An. parensis and 8.8% (n = 3) were An. rivulorum. The overall Plasmodium
falciparum sporozoite rate was 0.7% (n = 2,098). CONCLUSIONS: Pirimiphos-methyl
300 CS was found to be effective for IRS in the Lake Victoria basin,Tanzania. P
methyl 300 CShas a long residual efficacy on sprayed wall surfaces and therefore
it is effective in controlling principal malaria vectors of An. gambiae s.l and
An. funestus which rest on wall surfaces after and before feeding.
PMID- 28489936
TI - The association of dietary vitamin C intake with periodontitis among Korean
adults: Results from KNHANES IV.
AB - BACKGROUNDS: The association of dietary vitamin C (vit C) on periodontitis
requires more valid evidence from large representative samples to enable
sufficient adjustments. This study aimed to evaluate the association between
dietary vit C intake and periodontitis after controlling for various confounders
in the representative Korean adult population. METHOD: A total of 10,930 Korean
adults (>=19 years) from the fourth Korean National Health and Nutrition
Examination Survey data set were included in this cross-sectional study.
Periodontitis was defined as community periodontal index score of 3 or 4. Dietary
vit C intake was estimated from a 24-hour dietary record, and categorized into
adequate and inadequate according to the Korean Estimated Average Requirement
value. Potential confounders included age, sex, income, frequency of tooth
brushing, use of floss, dental visit, drinking, smoking, diabetes,
hypercholesterolemia, hypertension, and obesity. A multivariable logistic
regression analysis and stratified analysis were applied. RESULTS: Those with
inadequate dietary vit C intake were more likely by 1.16 times to have
periodontitis than those with adequate dietary vit C intake (adjusted odds ratio
[aOR] = 1.16, 95% confidence interval = 1.04-1.29). Lowest and middle-low
quartile of dietary vit C intake, compared to highest quartile of dietary vit C
intake, showed significant association (aOR = 1.28 and 1.22 respectively), which
was in a biological-gradient relationship (trend-p <0.05). CONCLUSIONS: Our data
showed that inadequate dietary vit C intake was independently associated with
periodontitis among Korean adults. Hence, adequate intake of dietary vitamin C
could be substantially important on the promotion of periodontal health among
Korean adults.
PMID- 28489937
TI - Impact of sublethal exposure to a pyrethroid-neonicotinoid insecticide on mating,
fecundity and development in the bed bug Cimex lectularius L. (Hemiptera:
Cimicidae).
AB - Sublethal exposure to an insecticide may alter insect feeding, mating,
oviposition, fecundity, development, and many other life history parameters. Such
effects may have population-level consequences that are not apparent in
traditional dose-mortality evaluations. Earlier, we found that a routinely used
combination insecticide that includes a pyrethroid and a neonicotinoid
(Temprid(r) SC) had deleterious effects on multiple bed bug (Cimex lectularius,
L.) behaviors. Here, we demonstrate that sublethal exposure impacts physiology
and reproduction as well. We report that sublethal exposure to Temprid SC has
variable aberrant effects on bed bugs depending on the strain, including: a
reduction in male mating success and delayed oviposition by females. However,
after sublethal exposure, egg hatch rate consistently declined in every strain
tested, anywhere from 34%-73%. Conversely, impact on fifth instar eclosion time
was not significant. While the strains that we tested varied in their respective
magnitude of sublethal effects, taken together, these effects could reduce bed
bug population growth. These changes in bed bug behavior and fecundity could lead
to improved efficacy of Temprid SC in the field, but recovery of impacted bugs
must be considered in future studies. Sublethal effects should not be overlooked
when evaluating insecticide efficacy, as it is likely that other products may
also have indirect effects on population dynamics that could either aid or
inhibit successful management of pest populations.
PMID- 28489938
TI - Metabolites contributing to Rhizoctonia solani AG-1-IA maturation and sclerotial
differentiation revealed by UPLC-QTOF-MS metabolomics.
AB - Rhizoctonia solani is a causative agent of sheath blight, which results in huge
economic losses every year. During its life cycle, the formation of sclerotia
helps Rhizoctonia solani withstand a variety of unfavorable factors. Oxidative
stress is a key factor that induces sclerotium formation. The differentiated and
undifferentiated phenotypes of R. solani AG-1-IA were obtained by controlling
aerial conditions. Metabolomics based on the mass spectrometry technique combined
with multivariate and univariate analyses was used to investigate the metabolic
variation in vegetative, differentiated and undifferentiated mycelia. Our results
revealed that during maturation, the metabolic levels of N2-acetyl-L-ornithine,
3,1'-(OH)2-Gamma-carotene, (5Z,7E)-(1S,3R)-24,24-difluoro-24a-homo-9,10-seco
5,7,10(19)-cholestatrien-1,3,25-triol, stoloniferone O, PA(O-18:0/12:0), PA(P
16:0/14:0), PA(P-16:0/16:(19Z)) and PA(P-16:0/17:2(9Z,12Z)) were suppressed in
both differentiated and undifferentiated mycelia. The concentrations of
PE(20:1(11Z)/14:1(9Z)), PE(P-16:0/20:4(5Z,8Z,11Z,13E)(15OH[S])) and
PS(12:0/18:1(9Z)) were increased in the differentiated group, while increased
levels of N(gamma)-nitro-L-arginine, tenuazonic acid and 9S,10S,11R-trihydroxy
12Z,15Z-octadecadienoic acid were found in the undifferentiated group. Our
results suggest that different levels of these metabolites may act as biomarkers
for the developmental stages of R. solani AG-1-IA. Moreover, the mechanisms of
sclerotium formation and mycelium differentiation were elucidated at the
metabolic level.
PMID- 28489939
TI - Prevalence of chronic stress in general practitioners and practice assistants:
Personal, practice and regional characteristics.
AB - BACKGROUND: The majority of studies investigating stress in primary care have
focused either on general practitioners (GPs) or practice assistants (PAs), but
did not measure stress on a practice level. We analyzed the prevalence of chronic
stress for both professional groups and on a practice level and investigated
personal, practice, and regional characteristics. METHODS: Chronic stress was
measured in GPs and PAs from 136 German practices using the standardized, self
administered TICS-SSCS questionnaire (12 items). Based on a sum-score,
participants per professional group were categorized as having low or high strain
due to chronic stress (<= 25th and >= 75th percentile of the study population's
distribution, respectively). For a cluster-level analysis, the mean of all
practice means was used to categorize low- and high-stress practices. The intra
class correlation coefficient (ICC) was calculated using ANOVA. Prevalence Ratios
(PR) were used to compare low versus high strain due to stress, stratified for
personal, practice and regional characteristics. RESULTS: The response rate was
74.1% (n = 137/185). Data from 214 GPs (34.1% female), 500 PAs (99.4% female),
and 50 PAs in training (98.0% female) were analyzed. Chronic stress was highest
in female GPs (median 19, IQR (interquartile range) 11.5), followed by PAs (16,
IQR 12.25) and male GPs (15, IQR 10). On a practice level, 26.3% of the practice
personnel reported a high stress level. We observed an overall ICC of 0.25, with
higher ICCs when stratifying by professional group (PAs: ICC 0.36, GPs in group
practices: ICC 0.51). High chronic stress was observed as the number of working
hours per week increased (GPs: PR 2.03, 95% CI 1.16-3.56; PAs: PR 2.02, 95% CI
1.22-3.35). There were no differences for practice type (solo/group) and the
various regional characteristics. CONCLUSION: Personal and practice
characteristics were associated with chronic stress in GPs, PAs, and on a
practice level. The high ICCs indicate a need for stress-reduction strategies
geared at both professions on a practice level.
PMID- 28489941
TI - Triboelectric Nanogenerator Enhanced Nanofiber Air Filters for Efficient
Particulate Matter Removal.
AB - We developed a high-efficiency rotating triboelectric nanogenerator (R-TENG)
enhanced polyimide (PI) nanofiber air filter for particulate matter (PM) removal
in ambient atmosphere. The PI electrospinning nanofiber film exhibited high
removal efficiency for the PM particles that have diameters larger than 0.5 MUm.
When the R-TENG is connected, the removal efficiency of the filter is enhanced,
especially when the particle diameters of the PM are smaller than 100 nm. The
highest removal efficiency is 90.6% for particles with a diameter of 33.4 nm and
the highest efficiency enhancement reaches 207.8% at the diameter of 76.4 nm
where the removal efficiency enhanced from 27.1% to 83.6%. This technology with
zero ozone release and low pressure drop offers an approach for air cleaning and
haze treatment.
PMID- 28489942
TI - Biotunable Nanoplasmonic Filter on Few-Layer MoS2 for Rapid and Highly Sensitive
Cytokine Optoelectronic Immunosensing.
AB - Monitoring of the time-varying immune status of a diseased host often requires
rapid and sensitive detection of cytokines. Metallic nanoparticle-based localized
surface plasmon resonance (LSPR) biosensors hold promise to meet this clinical
need by permitting label-free detection of target biomolecules. These biosensors,
however, continue to suffer from relatively low sensitivity as compared to
conventional immunoassay methods that involve labeling processes. Their response
speeds also need to be further improved to enable rapid cytokine quantification
for critical care in a timely manner. In this paper, we report an
immunobiosensing device integrating a biotunable nanoplasmonic optical filter and
a highly sensitive few-layer molybdenum disulfide (MoS2) photoconductive
component, which can serve as a generic device platform to meet the need of rapid
cytokine detection with high sensitivity. The nanoplasmonic filter consists of
anticytokine antibody-conjugated gold nanoparticles on a SiO2 thin layer that is
placed 170 MUm above a few-layer MoS2 photoconductive flake device. The principle
of the biosensor operation is based on tuning the delivery of incident light to
the few-layer MoS2 photoconductive flake thorough the nanoplasmonic filter by
means of biomolecular surface binding-induced LSPR shifts. The tuning is
dependent on cytokine concentration on the nanoplasmonic filter and
optoelectronically detected by the few-layer MoS2 device. Using the developed
optoelectronic biosensor, we have demonstrated label-free detection of IL-1beta,
a pro-inflammatory cytokine, with a detection limit as low as 250 fg/mL (14 fM),
a large dynamic range of 106, and a short assay time of 10 min. The presented
biosensing approach could be further developed and generalized for point-of-care
diagnosis, wearable bio/chemical sensing, and environmental monitoring.
PMID- 28489940
TI - Isolation and characterization of canine perivascular stem/stromal cells for bone
tissue engineering.
AB - For over 15 years, human subcutaneous adipose tissue has been recognized as a
rich source of tissue resident mesenchymal stem/stromal cells (MSC). The
isolation of perivascular progenitor cells from human adipose tissue by a cell
sorting strategy was first published in 2008. Since this time, the interest in
using pericytes and related perivascular stem/stromal cell (PSC) populations for
tissue engineering has significantly increased. Here, we describe a set of
experiments identifying, isolating and characterizing PSC from canine tissue (N =
12 canine adipose tissue samples). Results showed that the same antibodies used
for human PSC identification and isolation are cross-reactive with canine tissue
(CD45, CD146, CD34). Like their human correlate, canine PSC demonstrate
characteristics of MSC including cell surface marker expression, colony forming
unit-fibroblast (CFU-F) inclusion, and osteogenic differentiation potential. As
well, canine PSC respond to osteoinductive signals in a similar fashion as do
human PSC, such as the secreted differentiation factor NEL-Like Molecule-1 (NELL
1). Nevertheless, important differences exist between human and canine PSC,
including differences in baseline osteogenic potential. In summary, canine PSC
represent a multipotent mesenchymogenic cell source for future translational
efforts in tissue engineering.
PMID- 28489943
TI - Reduced Single Nucleotide Polymorphism Panels for Assigning Atlantic Albacore and
Bay of Biscay Anchovy Individuals to Their Geographic Origin: Toward Sustainable
Fishery Management.
AB - There is an increasing trend upon adding a detailed description of the origin of
seafood products driven by a general interest in the implementation of
sustainable fishery management plans for the conservation of marine ecosystems.
North Atlantic albacore ("Bonito del Norte con Eusko Label") and Bay of Biscay
anchovy ("Anchoa del Cantabrico") are two commercially important fish populations
with high economical value and vulnerable to commercial fraud. This fact,
together with the overexploited situation of these two populations, makes it
necessary to develop a tool to identify individual origin and to detect
commercial fraud. In the present study, we have developed and validated a
traceability tool consisting of reduced panels of gene-associated single
nucleotide polymorphisms (SNPs) suitable for assigning individuals of two species
to their origin with unprecedented accuracy levels. Only 48 SNPs are necessary to
assign 81.1% albacore and 93.4% anchovy individuals with 100% accuracy to their
geographic origin. The total accuracy of the results demonstrates how gene
associated SNPs can revolutionize food traceability. Gene-associated SNP panels
are not of mere commercial interest, but they also can result in a positive
impact on sustainability of marine ecosystems through conservation of fish
populations through establishing a more effective and sustainable fishery
management framework and contributing to the prevention of falsified labeling.
PMID- 28489944
TI - Studying the Crystallization of Various Polymorphic Forms of Nifedipine from
Binary Mixtures with the Use of Different Experimental Techniques.
AB - In this paper the crystal growth of nifedipine from pure system and from binary
mixtures composed of active substance (API) and two acetylated disaccharides,
maltose and sucrose (NIF-acMAL, NIF-acSUC, 5:1 weight ratio), was investigated.
Optical snapshots supported by X-ray diffraction (XRD) and Fourier transform
infrared spectroscopy (FTIR) measurements showed that mainly beta and alpha forms
of nifedipine grow up in all investigated samples. They also revealed that the
morphology of growing crystals strongly depends on the presence of modified
carbohydrates and temperature conditions. Interestingly, it was found that the
activation barrier for the crystal growth of the beta polymorph is not affected
by acetylated saccharides while the one estimated for the alpha form changes
significantly from 48.5 kJ/mol (pure API) up to 122 kJ/mol (NIF-acMAL system).
Moreover, the relationship between the crystal growth rate and structural
relaxation times for pure NIF and solid dispersions were analyzed. It turned out
that there is a clear decoupling between the crystal growth rate and structural
dynamics in both NIF-acMAL and NIF-acSUC binary mixtures. This is in line with
recent reports indicating the decoupling phenomenon to be a universal feature of
soft matter in the close vicinity of the glass transition temperature.
PMID- 28489945
TI - Quantifying Liquid Transport and Patterning Using Atomic Force Microscopy.
AB - Atomic force microscopy (AFM) provides unique insight into the nanoscale
properties of materials. It has been challenging, however, to use AFM to study
soft materials such as liquids or gels because of their tendency to flow in
response to stress. We propose an AFM-based technique for quantitatively
analyzing the transport of soft materials from an AFM probe to a surface.
Specifically, we present a method for loading an AFM probe with a single 0.3 to
30 pL droplet of liquid and subsequently measuring the mass of this liquid by
observing the change in the vibrational resonance frequency of the cantilever.
Using this approach, the mass of this liquid was detected with picogram-scale
precision by a commercial AFM system. Additionally, sub-femtoliter droplets of
liquid were transferred from the probe to a surface with agreement found between
the real-time change in mass of the liquid-loaded probe and the volume of the
feature written on the surface. To demonstrate the utility of this approach in
studying nanoscale capillary and transport phenomena, we experimentally determine
that the quantity of liquid transported from the tip to a surface in a given
patterning operation scales as the mass of liquid on the probe to the 1.35 power.
In addition to providing new avenues for studying the dynamics of soft materials
on the nanoscale, this method can improve nanopatterning of soft materials by
providing in situ feedback.
PMID- 28489946
TI - Transformation of Nitrogen and Evolution of N-Containing Species during Algae
Pyrolysis.
AB - Transformation and evolution mechanisms of nitrogen during algae pyrolysis were
investigated in depth with exploration of N-containing products under variant
temperature. Results indicated nitrogen in algae is mainly in the form of protein
N (~90%) with some inorganic-N. At 400-600 degrees C, protein-N in algae cracked
first with algae pyrolysis and formed pyridinic-N, pyrrolic-N, and quaternary-N
in char. The content of protein-N decreased significantly, while that of pyrrolic
N and quaternary-N increased gradually with temperature increasing. Pyridinic-N
and pyrrolic-N formation was due to deamination or dehydrogenation of amino
acids; subsequently, some pyridinic-N converted to quaternary-N. Increasing
temperature decreased amides content greatly while increased that of nitriles and
N-heterocyclic compounds (pyridines, pyrroles, and indoles) in bio-oil. Amides
were formed through NH3 reacting with fatty acids, that underwent dehydration to
form nitriles. Besides, NH3 and HCN yields increased gradually. NH3 resulted from
ammonia-N, labile amino acids and amides decomposition, while HCN came from
nitrile decomposition. At 700-800 degrees C, evolution trend of N-containing
products was similar to that at 400-600 degrees C. While N-heterocyclic
compounds in bio-oil mainly came from pyrifinic-N, pyrrolic-N, and quaternary-N
decomposition. Moreover, cracking of pyridinic-N and pyrrolic-N produced HCN and
NH3. A mechanism of nitrogen transformation during algae pyrolysis is proposed
based on amino acids decomposition.
PMID- 28489948
TI - Cellulose Nanocrystals/Polyacrylamide Composites of High Sensitivity and Cycling
Performance To Gauge Humidity.
AB - Cellulose nanocrystals (CNCs) have attracted much interest due to their unique
optical property, rich resource, environment friendliness, and templating
potentials. CNCs have been reported as novel photonic humidity sensors, which are
unfortunately limited by the dissolution and unideal moisture absorption of CNCs.
We, in this study, developed a high-performance photonic humidity composite
sensor that consisted of CNCs and polyacrylamide; chemical bonding was induced
between the two components by using glutaraldehyde as a bridging agent. The
composites inherited the chiral nematic structure of CNCs and maintained it well
through a cycling test. A distinct color change was observed for these composites
used as a humidity indicator; the change was caused by polyacrylamide swelling
with water and thus enlarging the helical pitch of the chiral nematic structure.
The composites showed no degradation of the sensing performance through cycling.
The excellent cycling stability was attributed to the bonding between
polyacrylamide and CNCs. This composite strategy can extend to the development of
other photonic indicators.
PMID- 28489947
TI - Determination of Ion Atmosphere Effects on the Nucleic Acid Electrostatic
Potential and Ligand Association Using AH+.C Wobble Formation in Double-Stranded
DNA.
AB - The high charge density of nucleic acids and resulting ion atmosphere profoundly
influence the conformational landscape of RNA and DNA and their association with
small molecules and proteins. Electrostatic theories have been applied to
quantitatively model the electrostatic potential surrounding nucleic acids and
the effects of the surrounding ion atmosphere, but experimental measures of the
potential and tests of these models have often been complicated by conformational
changes and multisite binding equilibria, among other factors. We sought a simple
system to further test the basic predictions from electrostatics theory and to
measure the energetic consequences of the nucleic acid electrostatic field. We
turned to a DNA system developed by Bevilacqua and co-workers that involves a
proton as a ligand whose binding is accompanied by formation of an internal AH+.C
wobble pair [Siegfried, N. A., et al. Biochemistry, 2010, 49, 3225]. Consistent
with predictions from polyelectrolyte models, we observed logarithmic dependences
of proton affinity versus salt concentration of -0.96 +/- 0.03 and -0.52 +/- 0.01
with monovalent and divalent cations, respectively, and these results help
clarify prior results that appeared to conflict with these fundamental models.
Strikingly, quantitation of the ion atmosphere content indicates that divalent
cations are preferentially lost over monovalent cations upon A.C protonation,
providing experimental indication of the preferential localization of more highly
charged cations to the inner shell of the ion atmosphere. The internal AH+.C
wobble system further allowed us to parse energetic contributions and extract
estimates for the electrostatic potential at the position of protonation. The
results give a potential near the DNA surface at 20 mM Mg2+ that is much less
substantial than at 20 mM K+ (-120 mV vs -210 mV). These values and difference
are similar to predictions from theory, and the potential is substantially
reduced at higher salt, also as predicted; however, even at 1 M K+ the potential
remains substantial, counter to common assumptions. The A.C protonation module
allows extraction of new properties of the ion atmosphere and provides an
electrostatic meter that will allow local electrostatic potential and energetics
to be measured within nucleic acids and their complexes with proteins.
PMID- 28489949
TI - Electronic Coupling between Graphene and Topological Insulator Induced Anomalous
Magnetotransport Properties.
AB - It has been theoretically proposed that the spin textures of surface states in a
topological insulator can be directly transferred to graphene by means of the
proximity effect, which is very important for realizing a two-dimensional
topological insulator based on graphene. Here we report the anomalous
magnetotransport properties of graphene-topological insulator Bi2Se3
heterojunctions, which are sensitive to the electronic coupling between graphene
and the topological surface state. The coupling between the pz orbitals of
graphene and the p orbitals of the surface states on the Bi2Se3 bottom surface
can be enhanced by applying a perpendicular negative magnetic field, resulting in
a giant negative magnetoresistance at the Dirac point up to about -91%. An
obvious resistance dip in the transfer curve at the Dirac point is also observed
in the hybrid devices, which is consistent with theoretical predictions of the
distorted Dirac bands with nontrivial spin textures inherited from the Bi2Se3
surface states.
PMID- 28489950
TI - Return of D4 Dopamine Receptor Antagonists in Drug Discovery.
AB - The dopamine D4 receptor garnered a great deal of interest in the early 1990s
when studies showed the atypical antipsychotic clozapine possessed higher
affinity for D4, relative to other dopamine receptor subtypes, and that this
activity might underlie the unique clinical efficacy of clozapine. Unfortunately,
D4 antagonists that were developed for schizophrenia failed in the clinic. Thus,
D4 fell out of favor as a therapeutic target, and work in this area was silent
for decades. Recently, D4 ligands with improved selectivity for D4 against not
only D1-3,5 but also other biogenic amine targets have emerged, and D4 is once
again in the spotlight as a novel target for both addiction and Parkinson's
disease (PD), as well as other emerging diseases. This report will review the
historical data for D4, review the known D4 ligands, and then highlight new data
supporting a role for D4 inhibition in addiction, PD, and cancer.
PMID- 28489951
TI - Direct Observation of Changes in Focal Conic Domains of Cholesteric Films Induced
by Ultraviolet Irradiation.
AB - The helical supramolecular structure of cholesteric liquid crystalline (LC) films
predetermines their outstanding optical properties and the unique nanostructure
of their surface. The introduction of photochromic dopants in these films opens
up an interesting possibility for creation of smart cholesteric materials with
photocontrollable optical and photovariable surface properties. Using atomic
force microscopy (AFM), we performed in situ measurements of the surface
topography of cyclosiloxane LC cholesteric oligomer films during the cholesteric
helix twisting caused by their preliminary ultraviolet (UV) irradiation. A chiral
photochromic isosorbide-based dopant was introduced in the films to control the
cholesteric helix pitch by UV-irradiation. The initial films are characterized by
planar texture with the presence of focal conic domains having the double-spiral
relief on their surface. UV-irradiation of these films leads to the cholesteric
helix twisting resulting in a decrease in the surface relief period, and the
enlargement of defect areas between the domains. The detailed mechanisms of the
rearrangement of the film surface structure due to the cholesteric helix twisting
are suggested. They include the rotation and displacement of cholesteric layers
in the bulk, and the nucleation of new ones at the surface in defect regions.
PMID- 28489952
TI - Revisiting Hydrogen Bond Thermodynamics in Molecular Simulations.
AB - In processes involving aqueous solutions and in almost every biomolecular
interaction, hydrogen bonds play important roles. Though weak compared to the
covalent bond, hydrogen bonds modify the stability and conformation of numerous
small and large molecules and modulate their intermolecular interactions. We
propose a simple methodology for extracting hydrogen bond strength from atomistic
level simulations. The free energy associated with hydrogen bond formation is
conveniently calculated as the reversible work required to reshape a completely
random pair probability distribution reference state into the one found in
simulations where hydrogen bonds are formed. Requiring only the probability
density distribution of donor-acceptor pairs in the first solvation shell of an
electronegative atom, the method uniquely defines the free energy, entropy, and
enthalpy of the hydrogen bond. The method can be easily extended to molecules
other than water and to multiple component mixtures. We demonstrate and apply
this methodology to hydrogen bonds that form in molecular dynamics simulations
between water molecules in pure water, as well as to bonds formed between
different molecules in a binary mixture of a sugar (trehalose) and water.
Finally, we comment on how the method should be useful in assessing the role of
hydrogen bonds in different molecular mechanisms.
PMID- 28489953
TI - Vascular function and arginine and dimethylarginines in gentamicin-induced renal
failure: a possible effect of heme oxygenase 1 inducer hemin.
AB - Increased oxidative stress and disturbance in nitric oxide bioavailability lead
to endothelial dysfunction and cardiovascular complication in renal disease.
Gentamicin (GM), a commonly used antibiotic, exhibits a toxic effect on renal
proximal tubules. Prevention of its nephrotoxicity is important. Therefore, we
investigated whether heme oxygenase 1 HO-1) induction influenced kidney and
vascular function in GM-administered rats. GM (100 mg.kg-1.day-1; i.p.) was given
to rats alone or together with hemin (20 mg.kg-1 on alternate days; i.p.) for 14
days. Plasma and kidney l-arginine, asymmetric dimethylarginine (ADMA), and
symmetric dimethylarginine (SDMA) as well as kidney 4-hydroxynonenal (HNE) levels
and myeloperoxidase (MPO) activity were measured. Histopathological examinations
of kidney and relaxation and contraction responses of aorta were also examined.
GM increased serum SDMA, urea nitrogen (BUN), and creatinine levels and caused
histopathological alterations in the kidney. GM elevated HO-1 protein and mRNA
expressions, 4-HNE level, and MPO activity and decreased antioxidant enzyme
activities and l-arginine levels in the kidney. Decreased relaxation and
contraction were detected in the aorta. Hemin restored renal oxidative stress and
inflammatory changes together with vascular dysfunction, but did not affect SDMA,
BUN, or creatinine levels. We conclude that HO-1 induction may be effective in
improving renal oxidative stress, inflammation, and vascular dysfunction mediated
by GM.
PMID- 28489954
TI - Astaxanthin Prevented Oxidative Stress in Heart and Kidneys of Isoproterenol
Administered Aged Rats.
AB - The objective of this study was to investigate the effect of astaxanthin on
isoproterenol (ISO)-induced myocardial infarction and cardiac hypertrophy in
rats. To evaluate the effect of astaxanthin on ISO-induced cardiac dysfunction,
18 aged Long Evans male rats were evenly divided into three groups. Group I
(Control group) was given only the laboratory-ground food and normal water. Group
II (ISO group) was administered ISO at a dose of 50 mg/kg subcutaneously (SC)
twice a week for two weeks. Group III (Astaxanthin + ISO group) was treated with
astaxanthin (25 mg/kg) orally every day and ISO 50 mg/kg SC twice a week for two
weeks. ISO administration in rats increased the heart and left ventricular wet
weights and increased inflammatory cell infiltration and fibrosis. Moreover, ISO
administration increased the lipid peroxidation and decreased antioxidant enzyme
activities in heart tissues. Astaxanthin treatment prevented the increased wet
weight of heart and decreased inflammatory cell infiltration and fibrosis. The
protective effect of astaxanthin was associated with reduction of free radicals
by improving antioxidant enzyme function, as well as normalization and/or
suppression of elevated oxidative stress markers, such as malondialdehyde (MDA),
nitric oxide (NO), and advanced protein oxidation product (APOP) in ISO
administered rats. Furthermore, astaxanthin decreased the elevated activities of
aspartate transaminase (AST), alanine transaminase (ALT), and creatinin kinase
muscle/brain (CK-MB) in ISO-administered rats. In conclusion, astaxanthin may
protect cardiac tissues in ISO-administered rats through suppression of oxidative
stress and enhancement of antioxidant enzyme functions.
PMID- 28489955
TI - Isometric and dynamic strength and neuromuscular attributes as predictors of
vertical jump performance in 11- to 13-year-old male athletes.
AB - In explosive contractions, neural activation is a major factor in determining the
rate of torque development, while the latter is an important determinant of jump
performance. However, the contribution of neuromuscular activation and rate of
torque development to jump performance in children and youth is unclear. The
purpose of this study was to examine the relationships between the rate of
neuromuscular activation, peak torque, rate of torque development, and jump
performance in young male athletes. Forty-one 12.5 +/- 0.5-year-old male soccer
players completed explosive, unilateral isometric and dynamic (240 degrees /s)
knee extensions (Biodex System III), as well as countermovement-, squat-, and
drop-jumps. Peak torque (pT), peak rate of torque development (pRTD), and rate of
vastus lateralis activation (Q30) during the isometric and dynamic contractions
were examined in relation to attained jump heights. Isometric pT and pRTD were
strongly correlated (r = 0.71) but not related to jump performance. Dynamic pT
and pRTD, normalized to body mass, were significantly related to jump height in
all 3 jumps (r = 0.38-0.66, p < 0.05). Dynamic normalized, but not absolute pRTD,
was significantly related to Q30 (r = 0.35, p < 0.05). In young soccer players,
neuromuscular activation and rate of torque development in dynamic contractions
are related to jump performance, while isometric contractions are not. These
findings have implications in the choice of training and assessment methods for
young athletes.
PMID- 28489956
TI - The Role of Chlorogenic Acid Supplementation in Anemia and Mineral Disturbances
Induced by 4-Tert-Octylphenol Toxicity.
AB - 4-tert-octylphenol (OP) is an endocrine-disrupting chemical that causes harmful
effects to human health. Chlorogenic acid is the major dietary polyphenol present
in various foods and beverages. The aim of the present study was to evaluate the
protective role of chlorogenic acid in anemia and mineral disturbance occurring
in OP toxicity in rats. Thirty-two male albino rats were divided into four equal
groups (8 rats/group) as follows. The first (control) group was treated daily
with an oral dose of 1 ml saline for two weeks. The second group was treated
daily with an oral dose of 60 mg chlorogenic acid/kg body weight for two weeks.
The third and fourth groups received daily intraperitoneal (ip) injections with
100 mg OP/kg body weight for two weeks; the fourth group was treated daily with
an oral dose of 60 mg chlorogenic acid/kg body weight for three weeks starting
one week before OP injections. The results revealed that OP induced significant
decreases in hemoglobin, hematocrit, red blood cells, mean cell volume, mean cell
hemoglobin, mean cell hemoglobin concentration, platelet count, white blood
cells, lymphocyte and neutrophil percent, transferrin receptor, serum calcium,
phosphorous, sodium, potassium, chloride, glutathione-S-transferase, glutathione
peroxidase, catalase, glutathione reductase, and superoxide dismutase. Moreover,
significant increases in serum hepcidin, ferritin, transferrin, erythropoietin,
aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, urea,
creatinine, selenium, zinc, manganese, copper, iron, malondialdehyde, and protein
carbonyl levels were found in OP groups. OP exposure also induced cell apoptosis.
Chlorogenic acid pretreatment in OP-treated groups restored all the mentioned
parameters to approach the normal values. In conclusion, chlorogenic acid
protects from anemia and mineral disturbances in 4-tert-octylphenol toxicity by
ameliorating oxidative stress and apoptosis.
PMID- 28489957
TI - Unravelling pathogenetic mechanisms of epidemic lineages.
PMID- 28489958
TI - Zinc metalloproteinase ZmpC suppresses experimental pneumococcal meningitis by
inhibiting bacterial invasion of central nervous systems.
AB - Streptococcus pneumoniae is a leading cause of bacterial meningitis. Here, we
investigated whether pneumococcal paralogous zinc metalloproteases contribute to
meningitis onset. Findings of codon-based phylogenetic analyses indicated 3 major
clusters in the Zmp family; ZmpA, ZmpC, and ZmpB, with ZmpD as a subgroup. In
vitro invasion assays of human brain microvascular endothelial cells (hBMECs)
showed that deletion of the zmpC gene in S. pneumoniae strain TIGR4 significantly
increased bacterial invasion into hBMECs, whereas deletion of either zmpA or zmpB
had no effect. In a mouse meningitis model, the zmpC deletion mutant exhibited
increased invasion of the brain and was associated with increased matrix
metalloproteinase-9 in plasma and mortality as compared with the wild type. We
concluded that ZmpC suppresses pneumococcal virulence by inhibiting bacterial
invasion of the central nervous system. Furthermore, ZmpC illustrates the
evolutional theory stating that gene duplication leads to acquisition of novel
function to suppress excessive mortality.
PMID- 28489959
TI - Mood disorders in adult asthma phenotypes.
AB - OBJECTIVE: Studies show high comorbidity of mood disorders in asthma. As asthma
is a highly heterogeneous disease with different phenotypes it can be expected
that there is a difference in this association with different asthma phenotypes.
The aim of our cross-sectional study was to assess the association of specific
asthma phenotypes with anxiety and/or depression and their impact on asthma
control. METHODS: A cross-sectional study in 201 consecutive adult outpatients
with asthma (>=18 years of age) was conducted. Each patient underwent physical
examination, detailed medical history, Hospital Anxiety and Depression Scale,
Asthma Control Questionnaire, Asthma Control Test, together with measurements of
lung function and fraction of exhaled nitric oxide. Phenotypes were assessed
using cluster analysis, and a multivariate analysis was used to identify
associations of mood disorders with different phenotypes. RESULTS: Five asthma
phenotypes were identified: allergic (AA, 43.8%), aspirin-exacerbated respiratory
disease (AERD, 21.9%), late-onset (LOA, 18.9%), obesity-associated (OAA, 10.0%),
and respiratory infections associated asthma (RIAA, 5.5%). A multivariate
analysis showed a significant association of anxiety with LOA and comorbid
hypertension (LOA, odds ratio (OR) = 2.12; hypertension, OR = 2.37, p = 0.012),
and depression with AA, RIAA, hypertension, and ACQ score (AA, OR = 6.07; RIAA,
OR = 4.73; hypertension, OR = 5.67; ACQ, OR = 1.87; p < 0.001). Comorbid
anxiety/depression was associated with AA, LOA, RIAA, hypertension, and ACQ score
(AA, OR = 10.15; LOA, OR = 2.98; RIAA, OR = 6.29; hypertension, OR = 5.15; ACQ,
OR = 1.90; p < 0.001. CONCLUSION: Mood disorders were significantly associated
with AA, LOA, and infection-associated asthma, together with comorbid
hypertension and the level of asthma control.
PMID- 28489960
TI - SWAP70 is a universal GEF-like adaptor for tethering actin to phagosomes.
AB - We recently identified a key role for SWAP70 as the tethering factor stabilizing
F-actin filaments on the surface of phagosomes in human dendritic cells by
interacting both with Rho-family GTPases and the lipid phosphatidylinositol (3,4)
bisphosphate. In this study, we aimed to investigate whether this role of SWAP70
was general among immune phagocytes. Our data reveal that SWAP70 is recruited to
early phagosomes of macrophages and dendritic cells from both human and mouse.
The putative inhibitor of SWAP70 sanguinarine blocked phagocytosis and F-actin
polymerization, supporting a key role for SWAP70 in phagocytosis as demonstrated
previously with knock-down. Moreover, SWAP70 was recently shown to sequester the
F-actin severing protein cofilin and we investigated this relationship in
phagocytosis. Our data show an increased activation of cellular cofilin upon
siRNA knockdown of SWAP70. Finally, we explored whether SWAP70 would be recruited
to the immune synapse between dendritic cells and T cells required for antigen
presentation, as the formation of such synapses depends on F-actin. However, we
observed that SWAP70 was depleted at immune synapses and specifically was
recruited to phagosomes. Our data support an essential and specific role for
SWAP70 in tethering and stabilizing F-actin to the phagosomal surface in a wide
range of phagocytes.
PMID- 28489961
TI - The role of Exo70 in exocytosis and beyond.
AB - The exocyst complex mediates the tethering of secretory vesicles to the plasma
membrane before SNARE-mediated membrane fusion. Recent studies have implicated
the exocyst in a wide range of cellular processes. Particularly, research on the
Exo70 subunit of the complex has linked the function of the exocyst in exocytosis
to cell adhesion, migration and invasion. In this review, we will discuss the
recent work on how Exo70 regulates these cellular processes, and how small
GTPases and kinases interact with Exo70 to orchestrate its function in exocytosis
and cytoskeleton organization. The study of Exo70 contributes to the
understanding of many pathophysiological processes from organogenesis to cancer
metastasis.
PMID- 28489962
TI - Development and validation of a screening procedure to identify speech-language
delay in toddlers with cleft palate.
AB - The purpose of this study was to develop and validate a clinically useful speech
language screening procedure for young children with cleft palate +/- cleft lip
(CP) to identify those in need of speech-language intervention. Twenty-two
children with CP were assigned to a +/- need for intervention conditions based on
assessment of consonant inventory using a real-time listening procedure in
combination with parent-reported expressive vocabulary. These measures allowed
evaluation of early speech-language skills found to correlate significantly with
later speech-language performance in longitudinal studies of children with CP.
The external validity of this screening procedure was evaluated by comparing the
+/- need for intervention assignment determined by the screening procedure to
experienced speech-language pathologist (SLP)s' clinical judgement of whether or
not a child needed early intervention. The results of real-time listening
assessment showed good-excellent inter-rater agreement on different consonant
inventory measures. Furthermore, there was almost perfect agreement between the
children selected for intervention with the screening procedure and the clinical
judgement of experienced SLPs indicate that the screening procedure is a valid
way of identifying children with CP who need early intervention.
PMID- 28489964
TI - Specific activation of PLEKHG2-induced serum response element-dependent gene
transcription by four-and-a-half LIM domains (FHL) 1, but not FHL2 or FHL3.
AB - PLEKHG2 is a Gbetagamma- and Galphas-dependent guanine nucleotide exchange factor
for Rac1 and Cdc42 small GTPases and has been shown to mediate signaling pathways
such as those for actin cytoskeletal reorganization and serum response element
(SRE)-dependent gene transcription. We have shown that the four-and-a-half LIM
domains (FHL) 1 acts as a positive regulator of PLEKHG2. Here, we evaluated the
other FHL family members and found that the FHL1A specifically regulate the
PLEKHG2 activity. Moreover, FHL1A further enhanced Gbetagamma- and PLEKHG2
induced SRE-dependent gene transcription, whereas FHL1A partially restored the
attenuated PLEKHG2-induced SRE-dependent gene transcription by Galphas. Our
results suggest that FHL1A specifically interacts with PLEKHG2 to regulate a
function of PLEKHG2 that is modified by the interaction of Gbetagamma and
Galphas.
PMID- 28489963
TI - The Aspergillus fumigatus farnesyltransferase beta-subunit, RamA, mediates
growth, virulence, and antifungal susceptibility.
AB - Post-translational prenylation mechanisms, including farnesylation and
geranylgeranylation, mediate both subcellular localization and protein-protein
interaction in eukaryotes. The prenyltransferase complex is an alphabeta
heterodimer in which the essential alpha-subunit is common to both the
farnesyltransferase and the geranylgeranyltransferase type-I enzymes. The beta
subunit is unique to each enzyme. Farnesyltransferase activity is an important
mediator of protein localization and subsequent signaling for multiple proteins,
including Ras GTPases. Here, we examined the importance of protein farnesylation
in the opportunistic fungal pathogen Aspergillus fumigatus through generation of
a mutant lacking the farnesyltransferase beta-subunit, ramA. Although
farnesyltransferase activity was found to be non-essential in A. fumigatus,
diminished hyphal outgrowth, delayed polarization kinetics, decreased conidial
viability, and irregular distribution of nuclei during polarized growth were
noted upon ramA deletion (DeltaramA). Although predicted to be a target of the
farnesyltransferase enzyme complex, we found that localization of the major A.
fumigatus Ras GTPase protein, RasA, was only partially regulated by
farnesyltransferase activity. Furthermore, the farnesyltransferase-deficient
mutant exhibited attenuated virulence in a murine model of invasive
aspergillosis, characterized by decreased tissue invasion and development of
large, swollen hyphae in vivo. However, loss of ramA also led to a Cyp51A/B
independent increase in resistance to triazole antifungal drugs. Our findings
indicate that protein farnesylation underpins multiple cellular processes in A.
fumigatus, likely due to the large body of proteins affected by ramA deletion.
PMID- 28489965
TI - Evidence for the subsynaptic zone as a preferential site for CHRN recycling at
neuromuscular junctions.
AB - Vertebrate skeletal muscle contraction is mediated by nicotinic acetylcholine
receptors (CHRN). Endocytosis and recycling of CHRN regulate their proper
abundance at nerve-muscle synapses, i.e. neuromuscular junctions. Recent work
showed that RAB5 is essential for CHRN endocytosis. Here, using in vivo-imaging
of endocytosed CHRN and RAB-GFP fusion proteins, we deliver evidence for
differential effects of RAB5-GFP, RAB4-GFP, and RAB11-GFP on CHRN endocytosis.
Furthermore, while newly endocytosed CHRN colocalized with RAB5-GFP over large
stretches of muscle fibers, RAB4-GFP and RAB11-GFP colocalized with endocytosed
CHRN almost exclusively at neuromuscular junctions. In agreement with previous
findings, this data suggests the existence of a specialized subsynaptic zone that
is particularly relevant for CHRN recycling.
PMID- 28489966
TI - Acrylamide-induced disturbance of the redox balance in the chick embryonic brain.
AB - This study was undertaken to determine the redox balance in the developing brain
after exposure to acrylamide (ACR), a potent neurotoxin. The studies were
performed using an in ovo chick embryo model. The antioxidant enzymes SOD, GPx,
CAT, and reduced glutathione (GSH) were used as indicators of the redox balance.
Eggs were injected with ACR doses of 40 mg kg-1 egg mass (2.4 mg egg-1) on
embryonic day 17 (E17). The activity of the antioxidant enzymes and the
concentration of GSH were measured at E17, E18, and E19 in the medulla oblongata,
cerebrum, cerebellum, and optic lobe. The results indicated a significant
decrease in the GSH concentrations in the optic lobe (E19, E20) and cerebrum
(E20) of embryos exposed to ACR. The activities of SOD and GPx were significantly
increased in the majority of the examined structures after injection of ACR. CAT
activity was completely inhibited in the brains of the embryos exposed to ACR
compared to that in the brains of the control embryos. Thus, we concluded that
ACR exerts a significant influence on the redox balance in the developing brain
by impacting the activity of antioxidant enzymes and the levels of GSH.
PMID- 28489968
TI - Tailoring Multicomponent Writing Interventions: Effects of Coupling Self
Regulation and Transcription Training.
AB - Writing proficiency is heavily based on acquisition and development of self
regulation and transcription skills. The present study examined the effects of
combining transcription training with a self-regulation intervention (self
regulated strategy development [SRSD]) in Grade 2 (ages 7-8). Forty-three
students receiving self-regulation plus transcription (SRSD+TR) intervention were
compared with 37 students receiving a self-regulation only (SRSD only)
intervention and 39 students receiving the standard language arts curriculum.
Compared with control instruction, SRSD instruction-with or without transcription
training-resulted in more complex plans; longer, better, and more complete
stories; and the effects transferred to story written recall. Transcription
training produced an incremental effect on students' composing skills. In
particular, the SRSD+TR intervention increased handwriting fluency, spelling
accuracy for inconsistent words, planning and story completeness, writing
fluency, clause length, and burst length. Compared with the SRSD-only
intervention, the SRSD+TR intervention was particularly effective in raising the
writing quality of poorer writers. This pattern of findings suggests that
students benefit from writing instruction coupling self-regulation and
transcription training from very early on. This seems to be a promising
instructional approach not only to ameliorate all students' writing ability and
prevent future writing problems but also to minimize struggling writers'
difficulties and support them in mastering writing.
PMID- 28489967
TI - Associations of the Polymorphisms in DHRS4, SERPING1, and APOR Genes with
Postmortem pH in Berkshire Pigs.
AB - Postmortem pH is a main factor influencing the meat quality in pigs. This study
investigated the association of postmortem pH with single-nucleotide
polymorphisms (SNPs) in the fourth member of the short-chain
dehydrogenase/reductase family (DHRS4), the first member of serpin peptidase
inhibitor, clade G (complement inhibitor) (SERPING1), and the apolipoprotein R
precursor (APOR) genes in Berkshire pigs. The study included 437 pigs, and
genotyping was conducted using the GoldenGate Assay (Illumina, San Diego, CA,
USA). DHRS4, SERPING1, and APOR polymorphisms were significantly associated with
pH45 or pH24 (p < 0.05). SERPING1 was also statistically significantly associated
with water holding capacity (p < 0.05), which is closely associated with
postmortem pH. These results suggest that SNPs in the DHRS4, SERPING1, and APOR
genes have potential for use as genetic markers for the meat quality in pigs.
PMID- 28489969
TI - Barriers toward help-seeking among young men prior to suicide.
AB - This study explores barriers to help-seeking among young men prior to suicide. We
analyzed 61 in-depth interviews with parents, siblings, friends, and ex-partners
of 10 young men (aged 18-30) with no record of mental illness, as well as 6
suicide notes, using interpretative phenomenological analysis. Three barriers
emerged: (a) a total defeat; (b) no room for weakness; and (c) fear of mental
disorder. The shame from falling short of standards (own/significant male
others') could be a considerable barrier to help-seeking in a suicidal crisis.
PMID- 28489970
TI - Photostability study of cis-configuration neonicotinoid insecticide cycloxaprid
in water.
AB - Cycloxaprid (CYC) is a new cis-configuration neonicotinoid insecticide, which is
currently under development in China for agricultural pest control. Considering
the photodegradation of CYC is important for the application of CYC in the
future, the photochemical behavior of CYC in aqueous solution was herein
investigated in a "merry-go-round" reactor under a 300 W high-pressure mercury
lamp. Twenty-five photodegradation products were identified via UPLC-TOF-ESI
MS/MS. The results suggested that NTN32692, the precursor of CYC was the
predominant photodegradation product. CYC photodegrades via a more complex
mechanism than imidacloprid and four potential photodegradation pathways were
proposed.
PMID- 28489971
TI - Phylogenetic systematics of Syncephalis (Zoopagales, Zoopagomycotina), a genus of
ubiquitous mycoparasites.
AB - We examined phylogenetic relationships among species of the mycoparasite genus
Syncephalis using sequences from three nuclear ribsosomal DNA genes (18S, 5.8S,
and 28S nuc rDNA) and a gene encoding the largest subunit of RNA polymerase II
(RPB1). Our data set included 88 Syncephalis isolates comprising 23 named species
and several unnamed taxa. We also revived a culturing technique using beef liver
and cellophane to grow several Syncephalis isolates without their host fungi to
obtain pure parasite DNA. Most isolates, however, were grown in co-cultures with
their host fungi, so we designed Syncephalis-specific primers to obtain sequence
data. Individual and combined data sets were analyzed by maximum likelihood (ML)
and Bayesian methods. We recovered 20 well-supported lineages and 38 operational
taxonomic units (OTUs). Most major clades contained isolates from distant
localities on multiple continents. There were taxonomic and nomenclature issues
within several clades, probably due to high phenotypic plasticity or species
dimorphism. We also conducted an analysis of Syncephalis nuc rDNA internal
transcribed spacer (ITS) sequences for 31 phylogenetically diverse isolates, and
we determined that most Syncephalis species have long ITS sequences relative to
other fungi. Although commonly employed eukaryotic and fungal primers are
compatible with diverse Syncephalis species, the ITS sequences of Syncepahlis are
nonetheless rarely recovered in environmental molecular diversity surveys.
PMID- 28489972
TI - Continuous bioelectricity generation through treatment of Victoria blue R: A
novel microbial fuel cell operation.
AB - A novel two-chamber microbial fuel cell (MFC) operation with a continuous
anaerobic-aerobic decolorization system was developed to improve the degradation
of the triphenylmethane dye, Victoria blue R (VBR). In addition, bioelectricity
was generated during the VBR degradation process, and the operation parameters
were optimized. The results indicated that the VBR removal efficiency and
electricity generation were affected by the VBR concentration, liquid retention
time (LRT), external resistance, gas retention time (GRT), and shock loading. The
optimal operation parameters were as follows: VBR concentration, 600 mg L-1; LRT,
24 h; external resistance, 3300 Omega; and GRT, 60 s. Under these operating
conditions, the VBR removal efficiency, COD removal efficiency, and power density
were 98.2% +/- 0.3%, 97.6% +/- 0.5%, and 30.6 +/- 0.4 mW m-2, respectively.
According to our review of the relevant literature, this is the first paper to
analyze the electrical characteristics of a continuous two-chamber MFC operation
and demonstrate the feasibility of the simultaneous electricity generation and
decolorization of VBR.
PMID- 28489973
TI - Selected aspects of the current state of freshwater resources in the Murmansk
region, Russia.
AB - Aspects of reducing the resource potential of surface waters of the Murmansk
region in the global climate change and the environment and their irrational use
have been considered. Increase of aquatic environment toxicity, drastic
restructuring of the structural and functional characteristics of aquatic
communities, changes in trophic status of lakes, reducing the stability of
freshwater ecosystems, increasing the risk of catastrophic degradation have been
shown. Taking into account the regional peculiarities, some indicators of surface
water quality in the Murmansk region have been proposed.
PMID- 28489974
TI - Diversity of the TLR4 Immunity Receptor in Czech Native Cattle Breeds Revealed
Using the Pacific Biosciences Sequencing Platform.
AB - The allelic variants of immunity genes in historical breeds likely reflect local
infection pressure and therefore represent a reservoir for breeding. Screening to
determine the diversity of the Toll-like receptor gene TLR4 was conducted in two
conserved cattle breeds: Czech Red and Czech Red Pied. High-throughput sequencing
of pooled PCR amplicons using the PacBio platform revealed polymorphisms, which
were subsequently confirmed via genotyping techniques. Eight SNPs found in coding
and adjacent regions were grouped into 18 haplotypes, representing a significant
portion of the known diversity in the global breed panel and presumably exceeding
diversity in production populations. Notably, the ancient Czech Red breed
appeared to possess greater haplotype diversity than the Czech Red Pied breed, a
Simmental variant, although the haplotype frequencies might have been distorted
by significant crossbreeding and bottlenecks in the history of Czech Red cattle.
The differences in haplotype frequencies validated the phenotypic distinctness of
the local breeds. Due to the availability of Czech Red Pied production herds, the
effect of intensive breeding on TLR diversity can be evaluated in this model. The
advantages of the Pacific Biosciences technology for the resequencing of long PCR
fragments with subsequent direct phasing were independently validated.
PMID- 28489975
TI - Biodegradation of airborne acetone/styrene mixtures in a bubble column reactor.
AB - The ability of a bubble column reactor (BCR) to biodegrade a mixture of styrene
and acetone vapors was evaluated to determine the factors limiting the process
efficiency, with a particular emphasis on the presence of degradation
intermediates and oxygen levels. The results obtained under varied loadings and
ratios were matched with the dissolved oxygen levels and kinetics of oxygen mass
transfer, which was assessed by determination of kLa coefficients. A 1.5-L
laboratory-scale BCR was operated under a constant air flow of 1.0 L.min-1, using
a defined mixed microbial population as a biocatalyst. Maximum values of
elimination capacities/maximum overall specific degradation rates of 75.5 gC.m
3.h-1/0.197 gC.gdw-1.h-1, 66.0 gC.m-3.h-1/0.059 gC.gdw-1.h-1, and 45.8 gC.m-3.h
1/0.027 gC.gdw-1.h-1 were observed for styrene/acetone 2:1, styrene-rich and
acetone-rich mixtures, respectively, indicating significant substrate
interactions and rate limitation by biological factors. The BCR removed both
acetone and styrene near-quantitatively up to a relatively high organic load of
50 g.m-3.h-1. From this point, the removal efficiencies declined under increasing
loading rates, accompanied by a significant drop in the dissolved oxygen
concentration, showing a process transition to oxygen-limited conditions.
However, the relatively efficient pollutant removal from air continued, due to
significant oxygen mass transfer, up to a threshold loading rate when the
accumulation of acetone and degradation intermediates in the aqueous medium
became significant. These observations demonstrate that oxygen availability is
the limiting factor for efficient pollutant degradation and that accumulation of
intermediates may serve as an indicator of oxygen limitation. Microbial
(activated sludge) analyses revealed the presence of amoebae and active nematodes
that were not affected by variations in operational conditions.
PMID- 28489976
TI - Testing the efficiency of extraction of incurred residues from soil with
optimized multi-residue method.
AB - The reproducibility of extraction of residues from spiked soil samples and from
soils containing incurred residues was tested with 14C-labeled test compounds of
different physical-chemical properties. Nearly 100% of the compounds added to the
sample before extraction could be recovered with an average reproducibility
relative standard deviation (CV) of 5.4%. The additional steps of the
determination process (cleanup, evaporation, etc.) contributed to the major part
of the variability of the results (CV = 10-20%). The incurred residues were most
efficiently extracted with acetone for 30 min followed by the mixture of
acetone/ethyl acetate 1:1 for additional 30 min. However, they could only be
recovered at various extent (64-90% of total residues), underlying the importance
of testing the efficiency of extraction. The residues were identified and
quantified by gas chromatography applying thermionic detector. The performance
parameters of the method complied with the international method validation
guidelines, and they proved to be robust and suitable for determination of
pesticide residues in soils of widely different physical-chemical properties.
PMID- 28489977
TI - Distribution of pesticide residues in soil and uncertainty of sampling.
AB - Pesticide residues were determined in about 120 soil cores taken randomly from
the top 15 cm layer of two sunflower fields about 30 days after preemergence
herbicide treatments. Samples were extracted with acetone-ethyl acetate mixture
and the residues were determined with GC-TSD. Residues of dimethenamid,
pendimethalin, and prometryn ranged from 0.005 to 2.97 mg/kg. Their relative
standard deviations (CV) were between 0.66 and 1.13. The relative frequency
distributions of residues in soil cores were very similar to those observed in
root and tuber vegetables grown in pesticide treated soils. Based on all
available information, a typical CV of 1.00 was estimated for pesticide residues
in primary soil samples (soil cores). The corresponding expectable relative
uncertainty of sampling is 20% when composite samples of size 25 are taken. To
obtain a reliable estimate of the average residues in the top 15 cm layer of soil
of a field up to 8 independent replicate random samples should be taken. To
obtain better estimate of the actual residue level of the sampled filed would be
marginal if larger number of samples were taken.
PMID- 28489978
TI - Sodium bisulfate and a sodium bisulfate/tannin mixture decreases pH when added to
an in vitro incubated poultry cecal or fecal contents while reducing Salmonella
Typhimurium marker strain survival and altering the microbiome.
AB - The objective of the present study was to investigate the ability of animal feed
grade sodium bisulfate (SBS) and a mixture of sodium bisulfate/tannin to inhibit
the growth of Salmonella using an anerobic in vitro mixed cecal culture to mimic
the conditions within the chicken cecum. An initial inoculum of Salmonella
Typhimurium was introduced to an anerobic dilution solution containing 1/3000
diluted cecal bacteria and solids consisting of ground chicken feed and different
percentages of solid SBS or SBS/tannin, and surviving organisms were enumerated.
Two different experimental designs were employed. In the "unadapted" treatment,
the S. Typhimurium was added at the beginning of the culture incubation along
with cecal bacteria and chicken feed/SBS or chicken feed/SBS/tannin. In the
"adapted" treatment, S. Typhimurium was added after a 24 hour pre-incubation of
the cecal bacteria with the chicken feed/SBS or chicken feed/SBS/tannin. Adding
SBS resulted in reduction of pH in the cultures which paralleled with the
reduction of S. Typhimurium. The SBS alone was found to be inhibitory to S.
Typhimurium in the adapted treatment at all concentrations tested (0.25, 0.5, and
0.75%), and the degree of inhibition was concentration-dependent. Salmonella
Typhimurium was completely killed in the adapted culture with 0.5% SBS after 24
and 48 h. The SBS/tannin mixture was less inhibitory than SBS alone at the same
concentrations in side-by-side comparisons. Testing at a 0.5% SBS concentration,
chicken age had little or no effect on log reduction of S. Typhimurium relative
to age-matched control cultures without SBS, but age did affect the absolute
number of S. Typhimurium surviving, with the greatest decreases occurring at 2
and 4 weeks of age (approx. 103 S. Typhimurium surviving) compared to 6 weeks of
age (approx. 105 Salmonella surviving). Microbiome analysis with an Illumina
MiSeq platform was conducted to investigate bacterial compositional changes
related to the addition of SBS. The relative abundance of Firmicutes (at the
phylum level) was decreased, and genera Lactobacillus and Faecalibacterium were
increased when SBS was added to the anaerobic mixed culture containing either
fecal or cecal material. The antimicrobial action of feed-grade SBS may represent
a potential pre-harvest control measure for Salmonella in poultry production.
PMID- 28489979
TI - Bending the Curve of Advanced Urothelial Carcinoma.
PMID- 28489980
TI - Practical Approach to Triple-Negative Breast Cancer.
AB - Triple negative is a term applied to breast cancers that do not meaningfully
express the estrogen or progesterone hormone receptors or overexpress the human
epidermal growth factor receptor 2 tyrosine kinase. At present, the only proven
method for systemic management of triple-negative breast cancer for both early
stage and metastatic settings is cytotoxic chemotherapy. Here, we provide a
comprehensive review of management strategies that are best supported by
available data. We also review recent advances most likely to affect treatment of
triple-negative breast cancer in the coming years with particular emphasis on
targeted agents, biologics, and immunotherapy.
PMID- 28489981
TI - Evolving Treatment of Advanced Urothelial Cancer.
AB - Urothelial cancer of the bladder is a smoking-related cancer and the fifth most
common cancer in the United States. At presentation, up to 25% of patients will
have muscle-invasive disease and, despite cystectomy or bladder-sparing
trimodality approaches, will develop metastatic disease. Cisplatin-based
combination chemotherapy regimens remain the standard of care in first-line
metastatic disease. Although response rates to these regimens are high, they are
rarely durable, and median overall survival is only 12 to 15 months. Treatment
options following progression on cisplatin-based regimens or for patients unfit
for cisplatin due to poor performance status, impaired renal function, or
comorbidities have been quite limited. However, there is now a new class of drugs
known as immune checkpoint inhibitors, which target the programmed cell death
1/programmed cell death-ligand 1 axis and promote antitumor immunity, that are
showing both efficacy and tolerability. These drugs have now been approved for
use in both cisplatin-treated and most recently cisplatin-unfit patients.
Clinical trials are currently ongoing to determine how best to use these drugs
and whether they should be used alone or in combination with other treatments.
This review will discuss the current standard of care in the management of
urothelial cancer and highlight recent trials of immunotherapy in this disease.
PMID- 28489982
TI - Triple-Negative Breast Cancer: Current Practice and Future Directions.
PMID- 28489983
TI - Outstanding Questions in the Clinical Management of Triple-Negative Breast
Cancer.
PMID- 28489984
TI - No Bridge Over Troubled Water: Slow Progress in Bladder Cancer.
PMID- 28489986
TI - Live to 70 Years and Older or Suffer in Silence: Understanding Health Insurance
Status Among the Elderly Under the NHIS in Ghana.
AB - Ghana has introduced a National Health Insurance Scheme (NHIS). Embedded in the
NHIS is a policy to exempt poor and vulnerable groups from premiums and user
fees. There has been some debate as to why the start-off age for exemption among
the elderly is 70 years. Ghana has a shorter life expectancy than middle- and
high-income countries and its current age of retirement is 60 years. This study
explores the financial and social implications of continuing to charge premiums
to people aged 60 to 69 years. Based on the analysis of data from a
representative household survey, it is recommended that the exemption policy
should be expanded to include all vulnerable elderly persons, regardless of age.
PMID- 28489985
TI - Preclinical evaluation of the imipridone family, analogs of clinical stage anti
cancer small molecule ONC201, reveals potent anti-cancer effects of ONC212.
AB - Anti-cancer small molecule ONC201 upregulates the integrated stress response
(ISR) and acts as a dual inactivator of Akt/ERK, leading to TRAIL gene
activation. ONC201 is under investigation in multiple clinical trials to treat
patients with cancer. Given the unique imipridone core chemical structure of
ONC201, we synthesized a series of analogs to identify additional compounds with
distinct therapeutic properties. Several imipridones with a broad range of in
vitro potencies were identified in an exploration of chemical derivatives. Based
on in vitro potency in human cancer cell lines and lack of toxicity to normal
human fibroblasts, imipridones ONC206 and ONC212 were prioritized for further
study. Both analogs inhibited colony formation, and induced apoptosis and
downstream signaling that involves the integrated stress response and Akt/ERK,
similar to ONC201. Compared to ONC201, ONC206 demonstrated improved inhibition of
cell migration while ONC212 exhibited rapid kinetics of activity. ONC212 was
further tested in >1000 human cancer cell lines in vitro and evaluated for safety
and anti-tumor efficacy in vivo. ONC212 exhibited broad-spectrum efficacy at
nanomolar concentrations across solid tumors and hematological malignancies. Skin
cancer emerged as a tumor type with improved efficacy relative to ONC201. Orally
administered ONC212 displayed potent anti-tumor effects in vivo, a broad
therapeutic window and a favorable PK profile. ONC212 was efficacious in vivo in
BRAF V600E melanoma models that are less sensitive to ONC201. Based on these
findings, ONC212 warrants further development as a drug candidate. It is clear
that therapeutic utility extends beyond ONC201 to include additional imipridones.
PMID- 28489987
TI - Bioengineering of an Intraabdominal Endocrine Pancreas.
PMID- 28489988
TI - CABG at 50 (or 107?) - The Complex Course of Therapeutic Innovation.
PMID- 28489989
TI - Left Ventricular Assist Devices for Advanced Heart Failure.
PMID- 28489990
TI - Left Ventricular Assist Devices for Advanced Heart Failure.
PMID- 28489991
TI - Case 14-2017 - A 20-Year-Old Man with Pain and Swelling of the Left Calf and a
Purpuric Rash
PMID- 28489992
TI - Arteriovenous Malformations of the Brain.
PMID- 28489993
TI - Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery.
PMID- 28489994
TI - Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery.
PMID- 28489995
TI - Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery.
PMID- 28489997
TI - New Lessons about Endometriosis - Somatic Mutations and Disease Heterogeneity.
PMID- 28489998
TI - Opioid Prescribing by Emergency Physicians and Risk of Long-Term Use.
PMID- 28489996
TI - Cancer-Associated Mutations in Endometriosis without Cancer.
AB - BACKGROUND: Endometriosis, defined as the presence of ectopic endometrial stroma
and epithelium, affects approximately 10% of reproductive-age women and can cause
pelvic pain and infertility. Endometriotic lesions are considered to be benign
inflammatory lesions but have cancerlike features such as local invasion and
resistance to apoptosis. METHODS: We analyzed deeply infiltrating endometriotic
lesions from 27 patients by means of exomewide sequencing (24 patients) or cancer
driver targeted sequencing (3 patients). Mutations were validated with the use of
digital genomic methods in microdissected epithelium and stroma. Epithelial and
stromal components of lesions from an additional 12 patients were analyzed by
means of a droplet digital polymerase-chain-reaction (PCR) assay for recurrent
activating KRAS mutations. RESULTS: Exome sequencing revealed somatic mutations
in 19 of 24 patients (79%). Five patients harbored known cancer driver mutations
in ARID1A, PIK3CA, KRAS, or PPP2R1A, which were validated by Safe-Sequencing
System or immunohistochemical analysis. The likelihood of driver genes being
affected at this rate in the absence of selection was estimated at P=0.001
(binomial test). Targeted sequencing and a droplet digital PCR assay identified
KRAS mutations in 2 of 3 patients and 3 of 12 patients, respectively, with
mutations in the epithelium but not the stroma. One patient harbored two
different KRAS mutations, c.35G->T and c.35G->C, and another carried identical
KRAS c.35G->A mutations in three distinct lesions. CONCLUSIONS: We found that
lesions in deep infiltrating endometriosis, which are associated with virtually
no risk of malignant transformation, harbor somatic cancer driver mutations. Ten
of 39 deep infiltrating lesions (26%) carried driver mutations; all the tested
somatic mutations appeared to be confined to the epithelial compartment of
endometriotic lesions.
PMID- 28489999
TI - Opioid Prescribing by Emergency Physicians and Risk of Long-Term Use.
PMID- 28490000
TI - Case 3-2017: A Man with Cardiac Sarcoidosis and New Diplopia and Weakness.
PMID- 28490001
TI - Zika Virus Vaccines - A Full Field and Looking for the Closers.
PMID- 28490002
TI - Survival and Neurodevelopment of Periviable Infants.
PMID- 28490003
TI - Binaural Tympanic-Membrane Perforations after Blast Injury.
PMID- 28490004
TI - Melanoma of the Foot.
PMID- 28490005
TI - Opposing Effects of Valproic Acid Treatment Mediated by Histone Deacetylase
Inhibitor Activity in Four Transgenic X. laevis Models of Retinitis Pigmentosa.
AB - Retinitis pigmentosa (RP) is an inherited retinal degeneration (RD) that leads to
blindness for which no treatment is available. RP is frequently caused by
mutations in Rhodopsin; in some animal models, RD is exacerbated by light.
Valproic acid (VPA) is a proposed treatment for RP and other neurodegenerative
disorders, with a phase II trial for RP under way. However, the therapeutic
mechanism is unclear, with minimal research supporting its use in RP. We
investigated the effects of VPA on Xenopus laevis models of RP expressing human
P23H, T17M, T4K, and Q344ter rhodopsins, which are associated with RP in humans.
VPA ameliorated RD associated with P23H rhodopsin and promoted clearing of mutant
rhodopsin from photoreceptors. The effect was equal to that of dark rearing, with
no additive effect observed. Rescue of visual function was confirmed by
electroretinography. In contrast, VPA exacerbated RD caused by T17M rhodopsin in
light, but had no effect in darkness. Effects in T4K and Q344ter rhodopsin models
were also negative. These effects of VPA were paralleled by treatment with three
additional histone deacetylase (HDAC) inhibitors, but not other antipsychotics,
chemical chaperones, or VPA structural analogues. In WT retinas, VPA treatment
increased histone H3 acetylation. In addition, electron microscopy showed
increased autophagosomes in rod inner segments with HDAC inhibitor (HDACi)
treatment, potentially linking the therapeutic effects in P23H rhodopsin animals
and negative effects in other models with autophagy. Our results suggest that the
success or failure of VPA treatment is dependent on genotype and that HDACi
treatment is contraindicated for some RP cases.SIGNIFICANCE STATEMENT Retinitis
pigmentosa (RP) is an inherited, degenerative retinal disease that leads to
blindness for which no therapy is available. We determined that valproic acid
(VPA), currently undergoing a phase II trial for RP, has both beneficial and
detrimental effects in animal models of RP depending on the underlying disease
mechanism and that both effects are due to histone deacetylase (HDAC) inhibition
possibly linked to autophagy regulation. Off-label use of VPA and other HDAC
inhibitors for the treatment of RP should be limited to the research setting
until this effect is understood and can be predicted. Our study suggests that,
unless genotype is accounted for, clinical trials for RP treatments may give
negative results due to multiple disease mechanisms with differential responses
to therapeutic interventions.
PMID- 28490006
TI - Adenoid Cystic Carcinoma of the Larynx Presenting as a Thyroid Mass and Brief
Literature Review.
AB - BACKGROUND: Adenoid cystic carcinoma (ACC) of the larynx and trachea is very
rare. CASE: A 45-year-old man with ACC of the larynx presenting as a thyroid mass
is reported in this study. Physical examination revealed a large solid thyroid
nodule in the left lobe without any lymphadenopathy. A technetium thyroid scan
showed multinodular goiter with cold nodules in the left lobe, isthmus, and
functioning nodules in the right lobe. A large thyroid mass originating from the
left side of the larynx, mostly the left vocal cord and the infraglottic part,
was seen using enhanced magnetic resonance imaging after rupture of the thyroid
cartilage on the left side. Ultrasound-guided fine needle aspiration smears and
cell blocks of the thyroid nodule showed highly cellular smears composed of large
tissue fragments, three-dimensional clusters, and sheets of neoplastic cells with
slightly enlarged round and hyperchromatic nuclei. Immunohistochemical study
showed that the cell block expressed C-kit and CK 7 on the cribriform growth
pattern of the tumoral cells. However, protein expression of thyroglobulin and
thyroid transcription factor-1 was not detectable. CONCLUSION: To approach a
thyroid nodule, direct invasion or metastatic tumors of other organs must be
borne in mind.
PMID- 28490007
TI - Duodenal Bulb Adenocarcinoma Benefitted from Neoadjuvant Chemotherapy: A Case
Report.
AB - Duodenal bulb adenocarcinoma is an extremely rare malignancy in the alimentary
tract which has a low incidence rate and nonspecific symptoms. It is difficult to
diagnose early, and the misdiagnosis rate is high. CT, MRI, upper
gastrointestinal endoscopy, and other advanced imaging modalities should be
combined to make a comprehensive evaluation. The diagnostic confirmation of this
tumor type mainly depends on the pathological examination. The combination of
surgery with other treatment modalities is effective. A review of reports on
duodenal bulb adenocarcinoma with chemotherapy revealed 6 cases since 1990.
However, there are few reports on neoadjuvant chemotherapy for the disease. In
this report, preoperative S-1 in combination with oxaliplatin neoadjuvant
chemotherapy achieved a complete pathological response in the treatment of
duodenal bulb adenocarcinoma. Neoadjuvant chemotherapy shows a better clinical
efficacy in the treatment of duodenal bulb adenocarcinoma, but its value needs to
be further verified.
PMID- 28490008
TI - An Uncommon ST1224 NDM-1-Producing Klebsiella pneumoniae Isolated from the
Bloodstream of a Leukemia Patient in China.
AB - AIMS: This study aimed to analyze the clinical data and characteristics of an NDM
1 (New Delhi metallo-beta-lactamase-1)-producing Klebsiella pneumoniae isolated
from the bloodstream of a leukemia patient. MATERIALS AND METHODS: A
retrospective analysis was used for the clinical data of the patient. The
modified Hodge test (MHT) and ethylenediaminetetraacetic acid (EDTA)-disk synergy
test were used for detecting metallo-beta-lactamase. Antibiotic resistance was
determined using the agar dilution method. PCR was used to identify resistance
genes. S1-PFGE (S1 nuclease/pulsed-field gel electrophoresis) and Southern blot
hybridization were performed to determine the location of blaNDM-1. A conjugation
experiment was used to confirm the transferable characteristics of the resistant
genes. Multilocus sequence typing (MLST) was also performed. RESULTS: The patient
developed bloodstream infections caused by this NDM-1-producing strain and died
due to worsening of the condition. The strain was highly resistant to beta-lactam
antibiotics and coharbored blaNDM-1, qnrB, and blaCTX-M-9 genes. Southern blot
confirmed that blaNDM-1 was located on a plasmid of approximately 55 kb and could
be transferred to Escherichia coli J53. MLST analysis showed that this strain
belonged to an uncommon sequence type ST1224. CONCLUSION: The coexistence of
various resistant genes is the mechanism for resistance to most antibiotics.
Additionally, infections caused by multi-drug resistant bacteria increase the
mortality of patients with immunodeficiency, which alerts clinicians to establish
a rational and effective combination drug therapy.
PMID- 28490009
TI - Clinicopathologic Study of Biliary Intraepithelial Neoplasia in
Cholangiocarcinoma.
AB - BACKGROUNDS AND AIMS: Biliary intraepithelial neoplasia (BilIN) is a precursor of
cholangiocarcinoma (CC) and it has been associated with several chronic
inflammatory conditions. This study aimed to elucidate the prevalence of BilIN in
CC and its clinicopathological significance. METHODS: Medical records of 193
patients with histologically confirmed CC were analyzed. We reviewed the
pathology findings of 48 patients who underwent curative surgery for CC. RESULTS:
Of the 48 patients analyzed, 34 and 14 patients had extrahepatic and intrahepatic
CC respectively. BilIN was detected in 28 patients (58%) and showed a
significantly higher prevalence in extrahepatic CC (75%) than in intrahepatic CC
(21%; p < 0.001). In the subgroup of 34 patients with extrahepatic CC, 25 and 9
patients were BilIN positive and negative respectively. Poor differentiation and
T3 stage were significantly more common in the BilIN-negative group than in the
BilIN-positive group (p < 0.05). The expression of MUC5AC, p53, and loss of Smad4
showed no difference between BilIN-positive CC and in BilIN-negative CC, but the
Ki-67 expression was significantly higher (p < 0.05). CONCLUSION: BilIN-positive
CC showed less invasiveness than negative cases. The Ki-67 expression was
significantly higher in BilIN-positive CC.
PMID- 28490010
TI - A Novel Approach of Synthesizing and Evaluating the Anticancer Potential of
Silver Oxide Nanoparticles in vitro.
AB - BACKGROUND: Development of novel strategies to kill cancer by sparing normal
cells is of utmost importance. Apart from their known antimicrobial activity,
only limited information has been recorded regarding the antitumor potential of
biocompatible silver oxide nanoparticles (AgONPs). There is a need to evaluate
the anticancer potential of biocompatible AgONPs in vitro. METHODS: A new
approach of utilizing the leaf extract of Excoecaria agallocha was used to
synthesize AgONPs. This was then characterized by ultraviolet-visible
spectrophotometry, nanoparticle-tracking analysis, and zeta-potential analysis.
Cytotoxicity and apoptotic potential were evaluated with an MTT assay and an
annexin V-binding assay against the murine melanoma (B16F10), murine colon cancer
(CT26), murine lung adenocarcinoma (3LL), and murine Ehrlich ascites carcinoma
(EAC) cell lines. Cellular localization of AgONPs was evaluated on fluorescence
microscopy. RESULTS: UV peaks at 270 and 330 nm indicated the formation of
nanoparticles (NPs) and the NP-tracking analyzer revealed them to have a size of
228 nm. AgONPs exerted initial cytotoxicity, specifically against all the
experimental malignant cells by sparing the normal cell lines. Moreover, AgONPs
exert apoptosis equally on all the malignant cells in vitro and ex vivo. This
cytotoxicity possibly occurs via the nuclear translocation of AgONPs as analyzed
in B16F10 cells. CONCLUSIONS: AgONPs utilizing natural sources would be a new
medicinal approach against a broad spectrum of malignancy.
PMID- 28490011
TI - New Interleukins in Psoriasis and Psoriatic Arthritis Patients: The Possible
Roles of Interleukin-33 to Interleukin-38 in Disease Activities and Bone
Erosions.
AB - OBJECTIVES: New interleukins (ILs), especially members of IL-1 and IL-12
families, have recently been reported to be involved in the development and
regulation of autoimmune and inflammatory diseases. In this study, we aimed to
explore the impact of these new ILs in psoriasis (Ps) and psoriatic arthritis
(PsA). METHODS: Forty PsA patients, 20 Ps patients, and 20 healthy controls (HCs)
were recruited. Blood samples were obtained for detecting the levels of ILs, IL
12/23p40, and tumor necrosis factor alpha (TNF-alpha). The severity of skin
lesions was assessed by the Psoriasis Area and Severity Index (PASI). Arthritis
activities of PsA patients were assessed by the PsA Joint Activity Index. For PsA
patients, circulating osteoclastogenesis-related cytokines (osteoprotegerin and
receptor activator of nuclear factor-kappaB ligand) and numbers of osteoclast
precursors were evaluated. Radiographic features of affected joints in these
patients were scored for erosion, joint-space narrowing, osteolysis, and new bone
formation. Correlations among levels of these ILs, Ps, and PsA disease activities
and bone erosions were studied. RESULTS: Ps and PsA patients had higher serum
levels of TNF-alpha, IL-12/23p40, and IL-33. Serum levels of IL-34 and IL-35 were
higher in PsA patients than in Ps patients and HCs. Patients with pustular Ps had
higher serum levels of IL-36alpha and IL-38 than patients with Ps vulgaris or
HCs. Increased serum levels of IL-36alpha were positively correlated with PASI.
CONCLUSION: Certain ILs were elevated in the circulation of patients with Ps and
PsA, which might contribute to the pathogenesis of skin lesions and arthritis.
PMID- 28490012
TI - Is the Prophylactic Use of Hepatoprotectants Necessary in Anti-Tuberculosis
Treatment?
AB - BACKGROUND: Liver injury is one of the serious side effects of anti-tuberculosis
(TB) drugs. It is controversial whether hepatoprotectant prophylaxis is efficient
and safe in anti-TB treatment, so we aimed to assess the efficacy and safety of
hepatoprotectant prophylaxis in patients who had received anti-TB treatment.
METHODS: PubMed, the Cochrane library, Embase, Ovid, Springer link, Wiley,
Elsevier, Web of Science, and the Karger Online Journal were systematically
searched prior to April 2016 for articles related to hepatoprotectant prophylaxis
in the treatment of TB. A meta-analysis was conducted to estimate the effect of
hepatoprotective agents on liver function and adverse events (AEs) in patients
who had received anti-TB drugs. The primary outcomes were changes in alanine
transaminase (ALT) and aspartate transaminase (AST) levels. The other outcomes
were drug-induced liver injury (DILI) and AEs. RESULTS: In our review, 6 trials
that involved 1,227 patients were included. Our analysis indicated that
hepatoprotective agents exerted protective effects on liver function in patients
who had received anti-TB drugs (weighted mean difference, WMD = -7.81, 95% CI [
12.26, -3.37], p = 0.0006 [ALT]; WMD = -7.07, 95% CI [-11.43, -2.72], p = 0.001
[AST]) in any age group. However, in the subgroup analysis of treatment duration,
the use of hepatoprotective agents was not associated with significant changes in
ALT and AST levels after 2 weeks of treatment and exhibited a positive effect on
liver function after 4 weeks of treatment. Moreover, the use of hepatoprotectants
significantly decreased the number of DILI cases (risk ratio, RR 0.50, 95% CI
[0.34-0.73], p = 0.0004). However, the use of hepatoprotectants led to similar
AEs in the control groups (RR 1.07, 95% CI [0.82-1.39], p = 0.62). CONCLUSIONS:
The use of hepatoprotective drugs may prevent liver injury in patients who are
receiving anti-TB drugs without any significant AEs 4 weeks after the initiation
of hepatoprotective medication.
PMID- 28490013
TI - Sulfatase 2 Modulates Fate Change from Motor Neurons to Oligodendrocyte Precursor
Cells through Coordinated Regulation of Shh Signaling with Sulfatase 1.
AB - Sulfatases (Sulfs) are a group of endosulfatases consisting of Sulf1 and Sulf2,
which specifically remove sulfate from heparan sulfate proteoglycans. Although
several studies have shown that Sulf1 acts as a regulator of sonic hedgehog (Shh)
signaling during embryonic ventral spinal cord development, the detailed
expression pattern and function of Sulf2 in the spinal cord remains to be
determined. In this study, we found that Sulf2 also modulates the cell fate
change from motor neurons (MNs) to oligodendrocyte precursor cells (OPCs) by
regulating Shh signaling in the mouse ventral spinal cord in coordination with
Sulf1. In the mouse, Sulf mRNAs colocalize with Shh mRNA and gradually expand
dorsally from embryonic day (E) 10.5 to E12.5, following strong Patched1 signals
(a target gene of Shh signaling). This coordinated expression pattern led us to
hypothesize that in the mouse, strong Shh signaling is induced when Shh is
released by Sulf1/2, and this strong Shh signaling subsequently induces the
dorsal expansion of Shh and Sulf1/2 expression. Consistent with this hypothesis,
in the ventral spinal cord of Sulf1 knockout (KO) or Sulf2 KO mice, the
expression patterns of Shh and Patched1 differed from that in wild-type mice.
Moreover, the position of the pMN and p3 domains were shifted ventrally, MN
generation was prolonged, and OPC generation was delayed at E12.5 in both Sulf1
KO and Sulf2 KO mice. These results demonstrated that in addition to Sulf1, Sulf2
also plays an important and overlapping role in the MN-to-OPC fate change by
regulating Shh signaling in the ventral spinal cord. However, neither Sulf1 nor
Sulf2 could compensate for the loss of the other in the developing mouse spinal
cord. In vitro studies showed no evidence of an interaction between Sulf1 and
Sulf2 that could increase sulfatase activity. Furthermore, Sulf1/2 double
heterozygote and Sulf1/2 double KO mice exhibited phenotypes similar to the Sulf1
KO and Sulf2 KO mice. These results indicate that there is a threshold for
sulfatase activity (which is likely reflected in the dose of Shh) required to
induce the MN-to-OPC fate change, and Shh signaling requires the coordinated
activity of Sulf1 and Sulf2 in order to reach that threshold in the mouse ventral
spinal cord.
PMID- 28490014
TI - Aryl Hydrocarbon Receptor Activation in Chronic Kidney Disease: Role of Uremic
Toxins.
AB - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
involved in the expression of xenobiotic-metabolizing enzymes, inflammatory
cytokines and adhesion molecules. Uremic toxins such as indoxyl sulfate and
indole acetic acid are derived from tryptophan fermentation by gut microbiota;
they accumulate in patients with chronic kidney disease (CKD) on haemodialysis
and have recently emerged as potent ligands of AhR. Therefore, AhR can serve as a
mediator in inflammation and cardiovascular diseases in these patients. This
review discusses current data that support a link between AhR activation and
uremic toxins from gut microbiota in CKD.
PMID- 28490015
TI - Salidroside Attenuates Ventilation Induced Lung Injury via SIRT1-Dependent
Inhibition of NLRP3 Inflammasome.
AB - BACKGROUND: Salidroside (SDS) is the main effective ingredient of Rhodiola rosea
L with a variety of pharmacologic properties. We aim to investigate the effects
of SDS on ventilation induced lung injury (VILI) and explore the possible
underlying molecular mechanism. METHODS: Lung injury was induced in male ICR mice
via mechanical ventilation (30 ml/kg) for 4h. The mice were divided in four
groups:(1) Control group; (2) Ventilation group; (3) SDS group; (4) Ventilation
with SDS group. SDS (50 mg/kg) was injected intraperitoneally 1h before
operation. Mouse lung vascular endothelial cells (MLVECs) were subjected to
cyclic stretch for 4h. RESULTS: It was found that SDS attenuated VILI as shown in
HE staining, cell count and protein content levels in BAL fluid, W/D and Evans
blue dye leakage into the lung tissue. SDS treatment inhibited the activation of
NLRP3 inflammasome and subsequent caspase-1 cleavage as well as interleukin (IL)
1beta secretion both in vivo and in vitro. Moreover, SDS administration up
regulated SIRT1 expression. Importantly, knockdown of SIRT1 reversed the
inhibitory effect of SDS on NLRP3 inflammasome activation. CONCLUSIONS: Taken
together, these findings indicate that SDS may confer protection against
ventilation induced lung injury via SIRT1-de-pendent inhibition of NLRP3
inflammasome activation.
PMID- 28490016
TI - Backup Mechanisms Maintain PACAP/VIP-Induced Arterial Relaxations in Pituitary
Adenylate Cyclase-Activating Polypeptide-Deficient Mice.
AB - BACKGROUND: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a
multifunctional neuropeptide in the VIP/secretin/glucagon peptide superfamily.
Two active forms, PACAP1-38 and PACAP1-27, act through G protein-coupled
receptors, the PAC1 and VPAC1/2 receptors. Effects of PACAP include potent
vasomotor activity. Vasomotor activity and organ-specific vasomotor effects of
PACAP-deficient mice have not yet been investigated; thus, the assessment of its
physiological importance in vasomotor functions is still missing. We hypothesized
that backup mechanisms exist to maintain PACAP pathway activity in PACAP knockout
(KO) mice. Thus, we investigated the vasomotor effects of exogenous vasoactive
intestinal peptide (VIP) and PACAP polypeptides in PACAP wild-type (WT) and PACAP
deficient (KO) male mice. METHODS: Carotid and femoral arteries were isolated
from 8- to 12-week-old male WT and PACAP-KO mice. Vasomotor responses were
measured with isometric myography. RESULTS: In the arteries of WT mice the
peptides induced relaxations, which were significantly greater to PACAP1-38 than
to PACAP1-27 and VIP. In KO mice, PACAP1-38 did not elicit relaxation, whereas
PACAP1-27 and VIP elicited significantly greater relaxation in KO mice than in WT
mice. The specific PAC1R and VPAC1R antagonist completely blocked the PACAP
induced relaxations. CONCLUSION: Our data suggest that in PACAP deficiency,
backup mechanisms maintain arterial relaxations to polypeptides, indicating an
important physiological role for the PACAP pathway in the regulation of vascular
tone.
PMID- 28490017
TI - Using Borderline Personality Organization to Predict Outcome after Total Knee
Arthroplasty.
PMID- 28490018
TI - Conflicts of Interest and the Presence of Methodologists on Guideline Development
Panels: A Cross-Sectional Study of Clinical Practice Guidelines for Major
Depressive Disorder.
PMID- 28490019
TI - Serious Games: The Future of Psychotherapy? Proposal of an Integrative Model.
PMID- 28490020
TI - Maternal Inflammation Results in Altered Tryptophan Metabolism in Rabbit Placenta
and Fetal Brain.
AB - Maternal inflammation has been linked to neurodevelopmental and neuropsychiatric
disorders such as cerebral palsy, schizophrenia, and autism. We had previously
shown that intrauterine inflammation resulted in a decrease in serotonin, one of
the tryptophan metabolites, and a decrease in serotonin fibers in the sensory
cortex of newborns in a rabbit model of cerebral palsy. In this study, we
hypothesized that maternal inflammation results in alterations in tryptophan
pathway enzymes and metabolites in the placenta and fetal brain. We found that
intrauterine endotoxin administration at gestational day 28 (G28) resulted in a
significant upregulation of indoleamine 2,3-dioxygenase (IDO) in both the
placenta and fetal brain at G29 (24 h after treatment). This endotoxin-mediated
IDO induction was also associated with intense microglial activation, an increase
in interferon gamma expression, and increases in kynurenine and the kynurenine
pathway metabolites kynurenine acid and quinolinic acid, as well as a significant
decrease in 5-hydroxyindole acetic acid (a precursor of serotonin) levels in the
periventricular region of the fetal brain. These results indicate that maternal
inflammation shunts tryptophan metabolism away from the serotonin to the
kynurenine pathway, which may lead to excitotoxic injury along with impaired
development of serotonin-mediated thalamocortical fibers in the newborn brain.
These findings provide new targets for prevention and treatment of maternal
inflammation-induced fetal and neonatal brain injury leading to
neurodevelopmental disorders such as cerebral palsy and autism.
PMID- 28490021
TI - Alexithymia and Psychotherapeutic Treatment Motivation: Main and Interactional
Effects on Treatment Outcome.
PMID- 28490022
TI - Concurrent Treatment with Prolonged Exposure for Co-Occurring Full or
Subthreshold Posttraumatic Stress Disorder and Substance Use Disorders: A
Randomized Clinical Trial.
AB - BACKGROUND: To test whether an integrated prolonged exposure (PE) approach could
address posttraumatic stress disorder (PTSD) symptoms effectively in individuals
with co-occurring substance use disorders (SUD), we compared concurrent treatment
of PTSD and SUD using PE (COPE) to relapse prevention therapy (RPT) for SUD and
an active monitoring control group (AMCG). METHODS: We conducted a randomized 12
week trial with participants (n = 110; 64% males; 59% African Americans) who met
Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text
revision criteria for full or subthreshold PTSD and SUD. Participants were
randomly assigned to COPE (n = 39), RPT (n = 43), or AMCG (n = 28). RESULTS: At
the end-of-treatment, COPE and RPT demonstrated greater reduction in PTSD symptom
severity relative to AMCG (COPE-AMCG = -34.06, p < 0.001; RPT-AMCG = -22.58, p =
0.002). Although the difference between COPE and RPT was not significant in the
complete sample, the subset of participants with full (vs. subthreshold) PTSD
demonstrated significantly greater reduction of PTSD severity in COPE relative to
RPT. Both treatments were superior to AMCG in reducing the days of primary
substance use (COPE-AMCG = -0.97, p = 0.01; RPT-AMCG = -2.07, p < 0.001).
Relative to COPE, RPT showed significantly more improvement in SUD outcome at end
of-treatment (RPT-COPE = -1.10, p = 0.047). At 3-month follow-up, COPE and RPT
maintained their treatment gains and were not significantly different in PTSD
severity or days of primary substance use. CONCLUSION: COPE and RPT reduced PTSD
and SUD severity in participants with PTSD + SUD. Findings suggest that among
those with full PTSD, COPE improves PTSD symptoms more than a SUD-only treatment.
The use of PE for PTSD was associated with significant decreases in PTSD symptoms
without worsening of substance use.
PMID- 28490023
TI - Cord Blood IL-16 Is Associated with 3-Year Neurodevelopmental Outcomes in
Perinatal Asphyxia and Hypoxic-Ischaemic Encephalopathy.
AB - Activation of the inflammatory pathway is increasingly recognized as an important
mechanism of injury following neonatal asphyxia and encephalopathy. This process
may contribute to the poor prognosis seen in some cases, despite therapeutic
hypothermia. Our group has previously identified raised interleukin (IL)-6 and IL
16, measured in umbilical cord blood at birth, to be predictive of grade of
hypoxic-ischaemic encephalopathy (HIE). Our aim in this study was to examine the
ability of these cytokines to predict the 3-year neurodevelopmental outcome in
the same cohort. As part of a prospective, longitudinal cohort study set in a
single tertiary maternity unit, term infants with biochemical and clinical
evidence of perinatal asphyxia were recruited at birth. Umbilical cord blood was
collected and analyzed for IL-6 and IL-16 using a Luminex assay. The
neurodevelopmental outcome of these infants was assessed at 3 years using the
Bayley Scales of Infant and Toddler Development (Edition 3). Early cord blood
measurement of IL-6 and IL-16 and long-term outcome were available in 33/69
infants. Median (IQR) IL-16 differentiated infants with a severely abnormal
outcome (n = 6) compared to all others (n = 27), (646 [466-1,085] vs. 383.5 [284
494] pg/mL; p = 0.012). IL-16 levels were able to predict a severe outcome with
an area under the receiver-operating characteristic (ROC) curve of 0.827 (95% CI
0.628-1.000; p = 0.014). Levels >=514 pg/mL predicted a severe outcome with a
sensitivity of 83% and a specificity of 81%. IL-16 also outperformed other
routine biochemical markers available at birth for the prediction of severe
outcome. APGAR scores at 1 and 10 min were also predictive of a severe outcome (p
= 0.022 and p = 0.036, respectively). A combination of IL-16 with these clinical
markers did not improve predictive value, but IL-16 combined with
electroencephalogram grading increased the area under the ROC curve. IL-6 did not
show any association with 3-year outcome. This is the first report studying the
association of IL-16 measured at birth with long-term outcome in a cohort of
neonates with perinatal asphyxia. IL-16 may be an early biomarker of severe
injury and aid in the long-term prognostication in infants with HIE.
PMID- 28490024
TI - A Novel Ataxic Mutant Mouse Line Having Sensory Neuropathy Shows Heavy Iron
Deposition in Kidney.
AB - BACKGROUND/AIMS: A novel ataxic mouse line was established from the offspring of
a male mouse administered cyclophosphamide in a juvenile period. METHODS: We have
attempted to examine the phenotype and histopathological changes of affected
mice. Furthermore, linkage analysis and sequencing of the mutant was performed to
reveal the causative gene locus. RESULTS AND CONCLUSION: The affected mouse was
characterized by heavy hind limb ataxia with gait disorder, which was first
recognized at about 4 weeks of age and slowly progressed with advancing age. The
phenotype was inherited in an autosomal recessive pattern. The genetic locus
associated with the phenotype was named hak and mapped to 107,305,356-108,637,615
on chromosome 2qE3, non-coding sequences in the vicinity of Bdnf gene. Many
spheroids were noticed in the cerebellar medulla and the brain stem. In the
peripheral nerves, some sensory ganglionic cells showed deposition of NF-200 in
the perikaryon and NF-200-positive spheroids in nerve fibers. No inflammatory
cell infiltration was observed. In addition, the adult affected mouse had
distinct iron deposition in the kidney and the liver, but not in the heart, the
skeletal muscle and the central nervous system. These results suggest that the
hak mouse has a tissue-specific impairment in the expression of a type of Bdnf
transcripts.
PMID- 28490025
TI - Group Cognitive Behavior Therapy Reversed Abnormal Spontaneous Brain Activity in
Adult Asthmatic Patients.
PMID- 28490026
TI - Cervical Esophagotomy for Removal of an Ingested Clam Shell: A Very Uncommon
Foreign Body Ingestion.
AB - OBJECTIVE: To report the removal of an ingested clam shell that was firmly
impacted in the esophagus. CLINICAL PRESENTATION AND INTERVENTION: A 77-year-old
man presented at our hospital with acute dysphagia after eating a seafood
risotto. An urgent dedicated examination (noncontrast helical multislice computed
tomography scan of the neck and flexible esophagoscopy) detected a clam shell
lodged in the upper esophagus. After several unsuccessful endoscopic attempts, a
lifesaving cervical esophagotomy was performed and the foreign body was
retrieved. CONCLUSION: This patient who ingested clam shell recovered well
following the retrieval of the foreign body by performing a lifesaving cervical
esophagotomy.
PMID- 28490027
TI - The Missed Diagnosis and Misdiagnosis of Pediatric Obesity.
PMID- 28490028
TI - Can We Jump from Cross-Sectional to Dynamic Interpretations of Networks?
Implications for the Network Perspective in Psychiatry.
PMID- 28490029
TI - Altered Dopamine Responses to Monetary Rewards in Female Fibromyalgia Patients
with and without Depression: A [11C]Raclopride Bolus-plus-Infusion PET Study.
PMID- 28490030
TI - Cognitive Behavior Therapy May Sustain Antidepressant Effects of Intravenous
Ketamine in Treatment-Resistant Depression.
AB - INTRODUCTION: Ketamine has shown rapid though short-lived antidepressant effects.
The possibility of concerning neurobiological changes following repeated exposure
to the drug motivates the development of strategies that obviate or minimize the
need for longer-term treatment with ketamine. In this open-label trial, we
investigated whether cognitive behavioral therapy (CBT) can sustain or extend
ketamine's antidepressant effects. METHODS: Patients who were pursuing ketamine
infusion therapy for treatment-resistant depression were invited to participate
in the study. If enrolled, the subjects initiated a 12-session, 10-week course of
CBT concurrently with a short 4-treatment, 2-week course of intravenous ketamine
(0.5 mg/kg infused over 40 min) provided under a standardized clinical protocol.
RESULTS: Sixteen participants initiated the protocol, with 8 (50%) attaining a
response to the ketamine and 7 (43.8%) achieving remission during the first 2
weeks of protocol. Among ketamine responders, the relapse rate at the end of the
CBT course (8 weeks following the last ketamine exposure) was 25% (2/8). On
longer-term follow-up, 5 of 8 subjects eventually relapsed, the median time to
relapse being 12 weeks following ketamine exposure. Among ketamine remitters, 3
of 7 retained remission until at least 4 weeks following the last ketamine
exposure, with 2 retaining remission through 8 weeks following ketamine exposure.
Ketamine nonresponders did not appear to benefit from CBT. CONCLUSIONS: CBT may
sustain the antidepressant effects of ketamine in treatment-resistant depression.
Well-powered randomized controlled trials are warranted to further investigate
this treatment combination as a way to sustain ketamine's antidepressant effects.
PMID- 28490031
TI - A Systematic Review of the Clinimetric Properties of the 6-Item Version of the
Hamilton Depression Rating Scale (HAM-D6).
AB - BACKGROUND: In a study aimed at identifying the items carrying information
regarding the global severity of depression, the 6-item Hamilton Depression
Rating Scale (HAM-D6) was derived from the original 17-item version of the scale
(HAM-D17). Since then, the HAM-D6 has been used in a wide range of clinical
studies. We now provide a systematic review of the clinimetric properties of HAM
D6 in comparison with those of HAM-D17 and the Montgomery Asberg Depression
Rating Scale (MADRS). METHODS: We conducted a systematic search of the literature
in PubMed, PsycInfo, and EMBASE databases in accordance with the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses guideline. Studies
reporting data on the clinimetric validity of the HAM-D6 and either the HAM-D17
or MADRS in non-psychotic unipolar or bipolar depression were included in the
synthesis. RESULTS: The search identified 681 unique records, of which 51
articles met the inclusion criteria. According to the published literature, HAM
D6 has proven to be superior to both HAM-D17 and MADRS in terms of scalability
(each item contains unique information regarding syndrome severity),
transferability (scalability is constant over time and irrespective of sex, age,
and depressive subtypes), and responsiveness (sensitivity to change in severity
during treatment). CONCLUSIONS: According to the published literature, the
clinimetric properties of HAM-D6 are superior to those of both the HAM-D17 and
MADRS. Since the validity of HAM-D6 has been demonstrated in both research and
clinical practice, using the scale more consistently would facilitate translation
of results from one setting to the other.
PMID- 28490033
TI - "Salami Slicing" in Pooled Analyses of Second-Generation Antipsychotics for the
Treatment of Depression.
PMID- 28490032
TI - Haplotype Based Analysis of XRCC3 Gene Polymorphisms in Thyroid Cancer.
AB - BACKGROUND/AIMS: In mammalian cells, XRCC3 plays an important role in the DNA
double-strand breaks (DSBs) repair by homologous recombination. Genetic
polymorphisms in XRCC3 gene may potentially affect the repair of DSBs and thus
confer susceptibility to thyroid cancer. In this study, we used a haplotype-based
approach to investigate whether 5 selected SNPs i.e. rs1799796, rs1799794,
rs861539, rs709399 and rs861530 of XRCC3 gene are associated with thyroid cancer
risk in 456 cancer patients and 400 cancer-free controls. METHODS: Genotyping was
performed using Allele-specific PCR followed by sequencing. Statistical analysis
was performed to analyse gene and haplotype association. RESULTS: After analysis,
frequency of mutant genotype/alleles of SNPs (rs1799796, p<0.0001; rs1799794,
p<0.0001; rs861539, p<0.001; rs709399, p <0.0001; rs861530, p<0.002) was found
significantly higher in thyroid cancer patients compared to controls. Significant
associations were found for most of the variant genotypes in SNPs of rs1799794,
rs1799796, rs861539, rs861530 and rs709399 in papillary thyroid and follicular
cancer patients compared to other histologic subtypes of thyroid carcinoma.
Additionally, haplotype analysis revealed that haplotypes, AACGA (p= 0.0005),
AGTAA (p= 0.008), GATAA (p= 0.001), GGCAA (p= 0.001) were linked with significant
increase in thyroid cancer risk. However, haplotype AGCGG (p= 0.0009) was
associated with a significant reduced thyroid cancer risk. CONCLUSION: Our
results suggest that common genetic variants in the XRCC3 gene of DSBR pathway
may modulate thyroid cancer risk.
PMID- 28490034
TI - Long Noncoding RNA CRNDE Promotes Proliferation of Gastric Cancer Cells by
Targeting miR-145.
AB - BACKGROUND/AIMS: The colorectal neoplasia differentially expressed (CRNDE) gene
is a long noncoding RNA (lncRNAs) that is upregulated in colorectal cancer and
glioma. Here, we investigated the regulatory function of CRNDE in gastric cancer
(GC). METHODS: CRNDE and miR-145 expression were assayed by qRT-PCR, and E2F3
protein expression was measured by western blotting. A luciferase reporter assay
was used to detect the direct regulation of miR-145 by CRNDE. Cell viability and
colony formation of human GC cells were detected using MTT and colony formation
assay, respectively. RESULTS: CRNDE was highly expressed in GC cell lines and
tissues; overexpression of CRNDE increased GC cell viability and promoted colony
formation. Knockdown of CRNDE did not result in loss of expression-related
effects on cell proliferation and colony formation. Further investigation
revealed that the miR-145 target gene E2F3 was strongly expressed following CRNDE
competitive molecular sponging of miR-145. CONCLUSION: CRNDE acted as a growth
promoting lncRNA in GC and maybe a potential target of GC treatment.
PMID- 28490035
TI - Clinical Pharmacopsychology: Conceptual Foundations and Emerging Tasks.
AB - The aim of this critical review was to outline emerging trends and perspectives
of clinical pharmacopsychology, an area of clinical psychology that is concerned
with the psychological effects of medications. The historical development of
clinical pharmacopsychology is outlined, with discussion of its most
representative expressions and reference to current challenges of clinical
research, with particular reference to clinimetrics. The domains of clinical
pharmacopsychology encompass the clinical benefits of psychotropic drugs, the
characteristics that predict responsiveness to treatment, the vulnerabilities
induced by treatment (side effects, behavioral toxicity, iatrogenic comorbidity),
and the interactions between drug treatment and psychological variables. Its aim
is to provide a comprehensive assessment of the clinical important changes that
are concerned with (a) wanted and expected treatment effects, (b) treatment
induced unwanted side effects, and (c) the patient's own personal experience of a
change in terms of well-being and/or quality of life. Clinical pharmacopsychology
offers a unifying framework for the understanding of clinical phenomena in
medical and psychiatric settings. Research in this area deserves high priority.
PMID- 28490036
TI - Fractured Penis: Not So Rare!
AB - INTRODUCTION: Penile fracture is a relatively common phenomenon. The main problem
associated with this condition is the lack of patients' awareness on the urgency
of the situation. This study reports the different modes of presentations and
treatment results. MATERIALS AND METHODS: We reviewed 21 cases of penile fracture
over 5 years. Parameters were mode of injury, age group, time interval before
presentation, management, site of injury, urethral involvement, results,
complications and erectile function at follow-up. RESULTS: The mean age of
patients was 34 years, the mean time interval until presentation was 26 h. Cases
involving the right corpus cavernosum comprised 57.14% and 42.85% were cases
involving the left corpus cavernosum. Two patients had full circumferential
urethral tear. Two patients developed wound infections and 2 patients developed
mild penile curvature (<30 degrees ). These 4 patients had all presented late for
treatment (>40 h). CONCLUSION: Urologists need to consider penile fracture a
urological emergency and atypical presentations need to be considered when
deciding on management.
PMID- 28490037
TI - Cyberchondria: Challenges of Problematic Online Searches for Health-Related
Information.
PMID- 28490038
TI - Pediatric sleep-disordered breathing: an update on diagnostic testing.
AB - PURPOSE OF REVIEW: Recent advances in diagnostic testing for obstructive sleep
apnea in children have refined the standard tests while identifying several new
tools that hold promise to radically change how we diagnose sleep apnea. RECENT
FINDINGS: Studies have demonstrated that the polysomnogram may be modified to
permit home assessment of sleep disturbed breathing in children to ensure more
widespread access to the test. Alternately, questionnaires, nocturnal oximetry,
and diagnostic urinary biomarkers have shown great promise as both sensitive and
specific tools to diagnose sleep apnea in children as well as track the severity
of the disease. SUMMARY: The gold standard polysomnogram has been refined to
permit its application in a modified form at home and for brief examinations in
children. This standard has been challenged on several fronts, including
questionnaires, nocturnal oximetry, drug-induced sleep endoscopy, and noninvasive
urinary biomarkers that may ultimately supplant polysomnography as the gold
standard to diagnose obstructive sleep apnea syndrome in children.
PMID- 28490039
TI - The implications of immunization in the daily practice of pediatric anesthesia.
AB - PURPOSE OF REVIEW: Vaccination is an important prevention measure, but requires
an intact immune system. Surgery and anesthesia suppress the immune system and
may interfere with the benefits of immunization. Moreover, common vaccine side
effects may be misinterpreted as postsurgical complications. This review
summarizes the essential basis of immunization and its potential interactions
with anesthesia. RECENT FINDINGS: Vaccines have mild side-effects, such as fever,
but may lead to serious complications in immunocompromised patients. Surgery and
anesthesia may decrease the efficacy of a vaccine, or promote vaccine-related
complications. It, therefore, reasonable to schedule surgery and anesthesia with
a delay either before or after vaccine administration, but there is no consensus
among anesthesiologists and pediatricians regarding this timing. SUMMARY:
Inactive vaccines are generally well tolerated. Live vaccines provide an
effective and long-lasting immunization, but may carry more serious
complications. Elective operations should be postponed 1 week after an inactive
vaccine and 3 weeks after immunization with a live vaccine. To avoid
misinterpretation of vaccine-related side-effects, vaccination should be also
delayed after surgery.
PMID- 28490040
TI - Individualized Plastic Reconstruction Strategy for Patients With Ectodermal
Dysplasia Syndrome.
AB - Ectodermal dysplasia syndrome is a hereditary disease of ectodermal origin.
Appearances of nail dystrophy, alopecia or hypotrichosis, saddle nose deformity,
and palmoplantar hyperkeratosis are usually associated with a lack of sweat
glands as well as partial or complete absence of teeth. These manifestations are
usually corrected only with oral rehabilitation by mounting dentures. In this
study, plastic rehabilitation was developed to correct the special features of
patients with ectodermal dysplasia. Four men and 1 woman with ectodermal
dysplasia syndrome were treated. Four patients showed dysostosis of the midface,
and rhinoplasty with costal bone was performed, whereas cosmetic operation aiming
to repair soft tissue defects was adopted for the last patient. After plastic
corrections, all 5 patients were satisfied with the results and had no social
embarrassment.
PMID- 28490041
TI - Hair Transplantation on a Free Microvascular Latissimus Dorsi Flap. Case Report:
Erratum.
PMID- 28490042
TI - Reply to "Different Ideas of Nodal Grouping in Standard and Extended
Lymphadenectomy During Pancreaticoduodenectomy for Pancreatic Head Cancer".
PMID- 28490043
TI - Chemical and Physical Exposures in the Emerging US Green-Collar Workforce.
AB - OBJECTIVE: "Green collar" workers serve in occupations that directly improve
environmental quality and sustainability. This study estimates and compares the
prevalence of select physical and chemical exposures among green versus non-green
U.S. workers. METHODS: Data from the U.S. 2010 National Health Interview Survey
(NHIS) Occupational Health Supplement were linked to the Occupational Information
Network (ONET) Database. We examined four main exposures: 1) vapors, gas, dust,
fumes (VGDF); 2) secondhand tobacco smoke; 3) skin hazards; 4) outdoor work.
RESULTS: Green-collar workers were significantly more likely to report exposure
to VGDF and outdoor work than nongreen-collar workers [adjusted odds ratio (AOR)
= 1.25; 95% CI = 1.11 to 1.40; AOR = 1.44 (1.26 to 1.63), respectively]. Green
collar workers were less likely to be exposed to chemicals (AOR = 0.80; 0.69 to
0.92). CONCLUSIONS: Green-collar workers appear to be at a greater risk for
select workplace exposures. As the green industry continues to grow, it is
important to identify these occupational hazards in order to maximize worker
health.
PMID- 28490044
TI - Dual Infection Contributes to Rapid Disease Progression in Men Who Have Sex With
Men in China.
AB - BACKGROUND: Considerable numbers of HIV-1-infected men who have sex with men
(MSM) show a relatively rapid disease progression in China; however, the cause
remains elusive. HIV-1 dual infection was reported to occur commonly among the
MSM population, and its contribution to clinical prognosis remains controversial.
We investigated the occurrence and impact on disease progression of dual
infection in a prospective MSM cohort in China. METHODS: Sixty-four HIV-1 early
infected participants were longitudinally followed up for 2 years. Deep
sequencing was used as dual-infection screening. CD4 T-cell counts and HIV-1
viral load were compared between coinfection and single-infection participants
and pre- versus post-superinfection. RESULTS: Eight coinfected participants and
10 superinfected participants were identified, including 9 participants with
intersubtype and 9 with intrasubtype dual infections. The prevalence of
coinfection was 13.1%, with a superinfection incidence of 15.6%. Coinfection
participants showed lower CD4 T-cell counts at 120 days after infection (P =
0.042) and a higher viral set point tendency (P = 0.053) as compared with single
infection participants. Kaplan-Meier analysis showed that the time for the viral
load to increase to above 4 log10 copies per milliliter was shorter in
coinfection participants than in single-infection participants (P < 0.001). After
superinfection, the median CD4 T-cell count decreased from 635 to 481 cells/MUL
(P = 0.027). CONCLUSIONS: The occurrence of dual infection among Chinese MSM is
relatively high, and HIV-1 dual infection might contribute to rapid disease
progression seen in the MSM population.
PMID- 28490045
TI - Uterine Inflammatory Myofibroblastic Tumors Frequently Harbor ALK Fusions With
IGFBP5 and THBS1.
AB - Inflammatory myofibroblastic tumor (IMT) can occur in a number of anatomic sites,
including the uterus. Like its soft tissue counterpart, uterine IMT frequently
expresses ALK and harbors ALK genetic rearrangements. The aim of this study is to
fully characterize the genetic fusions that occur in uterine IMT. We studied 11
uterine IMTs with typical histology and 8 uterine myxoid smooth muscle tumors (5
leiomyomas, 1 smooth muscle tumor of uncertain malignant potential, and 2
leiomyosarcomas) in which the differential of IMT was considered, using a RNA
sequencing-based fusion assay to detect genetic fusions involving ALK, ROS1, RET,
NTRK1/3, and other genes. ALK was expressed in 10 of 11 IMTs and 1 tumor
initially categorized as a myxoid leiomyoma (granular cytoplasmic staining with
paranuclear accentuation). Fusion transcripts involving ALK were identified in 9
of 10 ALK immunopositive IMTs, with 3 harboring IGFBP5-ALK, 3 harboring THBS1
ALK, 2 harboring FN1-ALK, and 1 harboring TIMP3-ALK. Among the smooth muscle
tumors, IGFBP5-ALK fusion transcript was identified in only 1 ALK immunopositive
case. Further review revealed that although a diagnosis of IMT was considered for
the ALK immunopositive myxoid leiomyoma, this diagnosis was not initially
rendered only because fluorescence in situ hybridization analysis was interpreted
as negative for ALK genetic rearrangement; this case is best reclassified as an
IMT. Notably, all the ALK fusions identified in our study included the
transmembrane domain-encoding exon 19 of ALK. Our findings confirm the high
frequency of ALK fusions in uterine IMT, with an enrichment of novel 5' ALK
fusion partners (IGFBP5, THBS1, and TIMP3) and exon 19-containing ALK fusion.
Given that IGFBP5 and FN1 are both situated on the same chromosome as ALK,
fluorescence in situ hybridization analysis for ALK rearrangement may not be
reliable and a negative result should not exclude a diagnosis of uterine IMT if
the histologic features and ALK immunostaining findings are supportive.
PMID- 28490047
TI - Development and Validation of an LC-MS/MS Method for the Simultaneous
Quantification of Abiraterone, Enzalutamide, and Their Major Metabolites in Human
Plasma.
AB - BACKGROUND: Abiraterone acetate and enzalutamide are 2 novel drugs for the
treatment of metastatic castration-resistant prostate cancer. The metabolism of
these drugs is extensive. Major metabolites are N-desmethyl enzalutamide,
enzalutamide carboxylic acid, abiraterone N-oxide sulfate, and abiraterone
sulfate; of which N-desmethyl enzalutamide is reported to possess antiandrogen
capacities. A liquid chromatography-tandem mass spectrometry method for
simultaneous quantification of abiraterone, enzalutamide, and the main
metabolites has been developed and validated to support therapeutic drug
monitoring. METHODS: Human plasma samples of patients treated with abiraterone or
enzalutamide were harvested at the clinic and stored at -20 degrees C. Proteins
were precipitated by acetonitrile, and the final extract was injected on a
Kinetex C18 column and separated with gradient elution. Analytes were detected by
liquid chromatography-mass spectrometry (Triple Quad 6500). RESULTS: The method
was validated over various linear ranges: 1-100 ng/mL for abiraterone, 5-500
ng/mL for enzalutamide and enzalutamide carboxylic acid, 10-1000 ng/mL for N
desmethyl enzalutamide, 30-3000 ng/mL for abiraterone N-oxide sulfate, and 100
10,000 ng/mL for abiraterone sulfate. Intra-assay and interassay variabilities
were within +/-15% of the nominal concentrations for quality control samples at
medium and high concentrations and within +/-20% at the lower limit of
quantification, respectively. CONCLUSIONS: The described method for simultaneous
determination of abiraterone and enzalutamide was validated successfully and
provides a useful tool for therapeutic drug monitoring in patients treated with
these agents.
PMID- 28490046
TI - Rapid Homogeneous Immunoassay to Quantify Gemcitabine in Plasma for Therapeutic
Drug Monitoring.
AB - BACKGROUND: Gemcitabine (2',2'-difluoro-2'-deoxycytidine) is a nucleoside analog
used as a single agent and in combination regimens for the treatment of a variety
of solid tumors. Several studies have shown a relationship between gemcitabine
peak plasma concentration (Cmax) and hematological toxicity. An immunoassay for
gemcitabine in plasma was developed and validated to facilitate therapeutic drug
monitoring (TDM) by providing an economical, robust method for automated
chemistry analyzers. METHODS: A monoclonal antibody was coated on nanoparticles
to develop a homogenous agglutination inhibition assay. To prevent ex vivo
degradation of gemcitabine in blood, tetrahydrouridine was used as a sample
stabilizer. Validation was conducted for precision, recovery, cross-reactivity,
and linearity on a Beckman Coulter AU480. Verification was performed on an AU5800
in a hospital laboratory. A method comparison was performed with (LC-MS/MS)
liquid chromatography tandem mass spectrometry using clinical samples.
Selectivity was demonstrated by testing cross-reactivity of the major metabolite,
2',2'-difluorodeoxyuridine. RESULTS: Coefficients of variation for repeatability
and within-laboratory precision were <8%. The deviation between measured and
assigned values was <3%. Linear range was from 0.40 to 33.02 MU/mL (1.5-125.5
MUM). Correlation with validated LC-MS/MS methods was R = 0.977. The assay was
specific for gemcitabine: there was no cross-reactivity to 2',2'
difluorodeoxyuridine, chemotherapeutics, concomitant, or common medications
tested. Tetrahydrouridine was packaged in single-use syringes. Gemcitabine
stability in whole blood was extended to 8 hours (at room temperature) and in
plasma to 8 days (2-8 degrees C). CONCLUSIONS: The assay demonstrated the
selectivity, test range, precision, and linearity to perform reliable
measurements of gemcitabine in plasma. The addition of stabilizer improved the
sample handling. Using general clinical chemistry analyzers, gemcitabine could be
measured for TDM.
PMID- 28490048
TI - Simultaneous Determination of Imatinib, Dasatinib, and Nilotinib by Liquid
Chromatography-Tandem Mass Spectrometry and Its Application to Therapeutic Drug
Monitoring.
AB - BACKGROUND: Imatinib, dasatinib, and nilotinib are tyrosine kinase inhibitors
(TKIs) used as first-line treatment of chronic myeloid leukemia. Therapeutic drug
monitoring is important to achieve treatment efficacy in the case of imatinib and
nilotinib, and to control toxicity in the case of dasatinib. New high-sensitivity
methods to monitor those drugs are needed, especially for dasatinib. Thus, a
simple method to determine plasma levels of imatinib, dasatinib, and nilotinib
for application in clinical practice was developed. METHODS: TKIs were eluted
with a Poroshell 120 EC-C18 column (2.1 * 75 mm, 2.7 MUm) at 0.5 mL/min and 60
degrees C, under gradient conditions through a mobile phase consisting of 4
mmol/L ammonium formate, pH 3.2 (65%), and acetonitrile (35%). TKIs were detected
and quantified by liquid chromatography in tandem with mass spectrometry (LC/MS
MS) with positive electrospray ionization and analytes were extracted using solid
phase extraction (Versaplate-SCX). Internal standards were isotope-labeled for
each analyte. RESULTS: The method was linear in the range of 2.5-5000 ng/mL for
imatinib, 0.75-400 ng/mL for dasatinib, and 2-4000 ng/mL for nilotinib. The
validation assays for accuracy and precision, matrix effect, extraction recovery,
carryover, and stability of the samples for all the TKIs were appropriate
according to regulatory agencies. Furthermore, imatinib plasma samples, stored
for 4 years at -80 degrees C were quite stable in approximately half of the
samples. CONCLUSIONS: The method enables rapid quantification of TKI
concentrations and is being applied to therapeutic drug monitoring to adjust dose
and to manage adverse reactions in clinical practice.
PMID- 28490050
TI - Is Trough Concentration of Vancomycin Predictive of the Area Under the Curve? A
Commentary.
PMID- 28490049
TI - Comparison of Plasma, Saliva, and Hair Levetiracetam Concentrations.
AB - BACKGROUND: Previous findings revealed high correlations between serum/plasma and
saliva levetiracetam concentrations, indicating saliva as an alternative matrix
for monitoring levetiracetam therapy. Levetiracetam concentration in the hair,
which could reflect long-term drug exposure and patients' compliance, has not
been systematically tested, as yet. The aim of this study was to determine the
correlation between plasma, saliva, and hair levetiracetam concentrations in 47
patients with epilepsy. METHODS: Plasma, saliva, and hair levetiracetam
concentrations were measured by liquid chromatography-tandem mass spectrometry
with positive ionization. RESULTS: Levetiracetam saliva and plasma concentrations
were highly correlated (r = 0.93). Plasma concentrations were not influenced by
sex, age, and other concomitant antiepileptic drugs. Levetiracetam hair
concentrations correlated with plasma concentrations (r = 0.36) but not daily
dose (mg/kg). Drug hair concentrations were not influenced by hair color or
treatment (dyed). CONCLUSIONS: The results tend to indicate that saliva may be a
reliable alternative to plasma for monitoring levetiracetam concentrations.
Levetiracetam can also be detected in human hair.
PMID- 28490051
TI - Comparison of flavour qualities of mushrooms (Flammulina velutipes) packed with
different packaging materials.
AB - To clarify the dynamic changes of flavour components in mushrooms packed with
different packaging materials during storage, comprehensive flavour
characterization, non-volatile and volatile compounds of Flammulina velutipes
were evaluated using electronic nose (E-nose), electronic tongue (E-tongue)
technology and headspace solid phase micro-extraction combined with gas
chromatography-mass spectrometry (HS-SPME-GC-MS), respectively. Results showed
that volatile compounds of fresh F. velutipes mainly consisted of ketones and
alcohols, with 3-octanone being the predominant compound. After storage, volatile
components significantly changed in mushrooms packed with normal packaging
material (Normal-PM) according to the GC-MS analysis and radar fingerprint chart
of electronic nose. The ethanol accumulation was inhibited by nanocomposite
packaging materials (Nano-PM). Besides, both radar graph and PCA of E-tongue
signals could differentiate the samples from different packaging and storage
time. In general, these results may provide a profile of flavour substances and
explain mechanism of flavour changes in F. velutipes over storage period.
PMID- 28490052
TI - Effects of endogenous cysteine proteinases on structures of collagen fibres from
dermis of sea cucumber (Stichopus japonicus).
AB - Autolysis of sea cucumber, caused by endogenous enzymes, leads to postharvest
quality deterioration of sea cucumber. However, the effects of endogenous
proteinases on structures of collagen fibres, the major biologically relevant
substrates in the body wall of sea cucumber, are less clear. Collagen fibres were
prepared from the dermis of sea cucumber (Stichopus japonicus), and the
structural consequences of degradation of the collagen fibres caused by
endogenous cysteine proteinases (ECP) from Stichopus japonicus were examined.
Scanning electron microscopic images showed that ECP caused partial
disaggregation of collagen fibres into collagen fibrils by disrupting
interfibrillar proteoglycan bridges. Differential scanning calorimetry and
Fourier transform infrared analysis revealed increased structural disorder of
fibrillar collagen caused by ECP. SDS-PAGE and chemical analysis indicated that
ECP can liberate glycosaminoglycan, hydroxyproline and collagen fragments from
collagen fibres. Thus ECP can cause disintegration of collagen fibres by
degrading interfibrillar proteoglycan bridges.
PMID- 28490053
TI - Prebiotic effect of xylooligosaccharides produced from birchwood xylan by a novel
fungal GH11 xylanase.
AB - A fungal endoxylanase belonging to the glycoside hydrolase gene family 11 (GH11)
was obtained from the ascomycete Talaromyces amestolkiae. The enzyme was
purified, characterized and used to produce a mixture of xylooligosaccharides
(XOS) from birchwood xylan. A notable yield of neutral XOS was obtained (28.8%)
upon enzyme treatment and the mixture contained a negligible amount of xylose,
having xylobiose, xylotriose and xylotetraose as its main components. The
prebiotic potential of this mixture was demonstrated upon analyzing the
variations in microorganisms' composition and organic acids profile in breast-fed
child faeces fermentations. The strong production of acetic and lactic acid, the
decrease of potentially pathogenic bacteria and the increase of bifidobacteria,
and possible beneficial commensals, confirmed the prebiotic value of these
xylooligosaccharides.
PMID- 28490054
TI - Evaluation of processing effects on anthocyanin content and colour modifications
of blueberry (Vaccinium spp.) extracts: Comparison between HPLC-DAD and CIELAB
analyses.
AB - Colour is the first organoleptic property that consumers appreciate of a
foodstuff. In blueberry (Vaccinium spp.) fruits, the anthocyanins are the
principal pigments determining the colour as well as many of the beneficial
effects attributed to this functional food. Commercial blueberry-derived products
represent important sources of these healthy molecules all year round. In this
study, blueberries were produced into purees comparing two homogenization methods
and further heated following different thermal treatments. All the supernatants
of the homogenates were monitored for pH. Then, the hydroalcoholic extracts of
the same samples were characterized by CIELAB and HPLC-DAD analyses. These
analytical techniques provide complementary information on fruit pigments content
as a whole and on quali-quantitative profile of the single bioactive colorants.
These data could be very interesting to know the best manufacturing procedure to
prepare blueberry-derived products, well accepted by the consumers, while
maintaining their healthy properties unaltered.
PMID- 28490055
TI - Carotenoid bioaccessibility and the relation to lipid digestion: A kinetic study.
AB - The micellar incorporation of carotenoids (lycopene, alpha- and beta-carotene)
and lipid digestion products (free fatty acids, FFAs, and monoacylglycerides,
MAGs) during in vitro digestion of oil-in-water emulsions was investigated by a
kinetic approach. A fractional conversion model could adequately describe the
hydrolysis of triacylglycerides, formation of FFAs and MAGs, and micellar
incorporation of carotenoids, FFAs and MAGs. The release of FFAs and MAGs from
TAGs proceeded faster than their incorporation into micelles. Rate constants of
carotenoid micellar incorporation were inversely proportional to their
hydrophobicity and dependent on the isomeric configuration, being the
incorporation of the cis faster than their all-trans isomers. Furthermore, a
positive linear relation was found between the micellar incorporation of
carotenoids and lipid digestion products. The isomeric form of carotenoids did
not affect such relation. The present kinetic approach can be useful to gain
mechanistic insight into carotenoid bioaccessibility as affected by various
process- and product-related factors.
PMID- 28490057
TI - Surface molecularly imprinted polymer capped Mn-doped ZnS quantum dots as a
phosphorescent nanosensor for detecting patulin in apple juice.
AB - A Mn-doped ZnS quantum dots (QDs) based nanosensor for selective phosphorescent
determination of patulin (PAT) was synthesized with 6-hydroxynicotinic acid (6
HNA) as dummy template via a surface molecular imprinting sol-gel process. FTIR
and XRD indicated the successful graft of molecularly imprinted polymer (MIP)
onto crystal QDs. Binding tests revealed that the MIP-QDs presented higher
selectivity, adsorption capacity and mass transfer rate than non-imprinted
polymers, demonstrating a specific recognition for PAT among competitive
mycotoxins and its analogues with the imprinting factor of 2.02. The MIP-QDs
could recognize PAT in a linear range of 0.43-6.50MUmolL-1 with a detection limit
of 0.32MUmolL-1 and a correlation coefficient (R2) of 0.9945. Recoveries of 102.9
127.2% with relative standard deviations <4.95% were achieved in apple juice
samples which were in good agreement with high-performance liquid chromatography
(HPLC) (P>0.05). The results indicated a simple phosphorescent nanosensor for PAT
detection in complex matrix.
PMID- 28490056
TI - Roles of different initial Maillard intermediates and pathways in meat flavor
formation for cysteine-xylose-glycine model reaction systems.
AB - To explore initial Maillard reaction pathways and mechanisms for maximal
formation of meaty flavors in heated cysteine-xylose-glycine systems, model
reactions with synthesized initial Maillard intermediates, Gly-Amadori, TTCA (2
threityl-thiazolidine-4-carboxylic acids) and Cys-Amadori, were investigated.
Relative relativities were characterized by spectrophotometrically monitoring the
development of colorless degradation intermediates and browning reaction
products. Aroma compounds formed were determined by solid-phase microextraction
combined with GC-MS and GC-olfactometry. Gly-Amadori showed the fastest reaction
followed by Cys-Amadori then TTCA. Free glycine accelerated reaction of TTCA,
whereas cysteine inhibited that of Gly-Amadori due to association forming
relatively stable thiazolidines. Cys-Amadori/Gly had the highest reactivity in
development of both meaty flavors and brown products. TTCA/Gly favored yielding
meaty flavors, whereas Gly-Amadori/Cys favored generation of brown products.
Conclusively, initial formation of TTCA and pathway involving TTCA with glycine
were more applicable to efficiently produce processed-meat flavorings in a
cysteine-xylose-glycine system.
PMID- 28490058
TI - A cold active transglutaminase from Antarctic krill (Euphausia superba):
Purification, characterization and application in the modification of cold-set
gelatin gel.
AB - Transglutaminase (TGase), EC 2.3.2.13, was purified from whole Antarctic krill
(Euphausia superba) using ammonium sulfate fractionation and DEAE-Sephacel
chromatography. The purified enzyme had specific activity, purification fold and
yield of 53.518U/mg, 10.272 and 10.992%, respectively. The molecular weight of
the purified Antarctic krill TGase was estimated to be 78kDa using sodium dodecyl
sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The optimal pH and
temperature for the activity of the purified TGase were pH 8.0-9.0 and 0-10
degrees C, respectively. However, the TGase activity reduced to 50% at a higher
temperature of 45 degrees C. The cations Ca++ and Na+ activated the purified
TGase activity optimally at levels of incorporation of 10mM and 1.8mM,
respectively. Addition of TGase at 0.1U/mg increased the gel strength (p<0.05),
setting temperature, setting time (p<0.05) and melting temperature (p<0.05) of
cold-set gelatin gel.
PMID- 28490059
TI - Lipid classes and fatty acids composition of the roe of wild Silurus glanis from
subalpine freshwater.
AB - The fat content and the fatty acid composition of the roe of European catfish
(Silurus glanis) wild specimens captured in the Lambro river basin (Como,
Northern Italy) were investigated in order to assess their nutritional value.
Total extracted lipid values on roe weight were 5.8-6.3%. Phospholipids (40.2
43.6%) and triacylglycerols (31.8-34.7%) were the most represented lipid classes.
Relevant amount of cholesteryl esters (14.3-15.6%) were also detected. The main
fatty acids were palmitic, oleic and cis-4,7,10,13,16,19-docosahexaenoic acid
(DHA). Total saturated fatty acids were 28.1-30.9%, monounsaturated fatty acids
were 28.2-30.6%, and polyunsaturated fatty acids (PUFAs) were 26.7-29.1%. The
good found content of phospholipids and omega3-polyunsaturated fatty acids
encourage further investigation for the exploitation of Silurus glanis roe in
food products and/or supplements.
PMID- 28490060
TI - Determination of flubendiamide in honey at trace levels by using solid phase
extraction and liquid chromatography coupled to quadrupole time-of-flight mass
spectrometry.
AB - In this study, a new method has been developed to determine flubendiamide in
honey using liquid chromatography coupled to a selective mass spectrometry
detector (quadrupole-time-of-flight). An efficient sample treatment involving a
solid phase extraction with a C18 sorbent was proposed (average analyte
recoveries were between 94 and 104%). Chromatographic analysis (9min) was
performed on a C18 column (Gemini C18, 50*2.0mm, 3um, 110A). The mobile phase
consisted of water and acetonitrile, with a flow rate of 0.5mL/min in gradient
elution mode. The method was fully validated in terms of selectivity, limits of
detection and quantification, matrix effect, linearity, trueness and precision.
Low limits of detection and quantification were obtained, ranging from 0.1 to
0.2ug/kg and 0.4 to 0.6ug/kg, respectively. The method was applied to analyze
flubendiamide in honey from different botanic origins (multifloral, rosemary and
heather).
PMID- 28490061
TI - The inclusion complex of oxyresveratrol in modified cyclodextrins: A
thermodynamic, structural, physicochemical, fluorescent and computational study.
AB - The interaction between oxyresveratrol (a type of stilbene with high biological
activity) and modified cyclodextrins (CDs) was studied. Using HPLC-RP, was seen
to form a 1:1 complex with all the CDs tested. The best CD in this respect was
MbetaCD (KF=606.65+/-30.18M-1), the complexation showing a strong dependence on
pH and temperature: The complexation constant (KF) decreased as the pH and
temperature increased. The thermodynamic parameters studied (DeltaH degrees ,
DeltaS degrees and DeltaG degrees ) showed negative entropy, enthalpy and Gibbs
free energy change at 25 degrees C. In addition, fluorescence signal of
oxyresveratrol increased when MbetaCD was added. The oxyresveratrol emission and
excitation spectra were obtained for first time. A 1H NMR was carried out to
study the structure of the complex and, DSC studied demonstrated the
complexation. A computational study by molecular docking was made to complement
the structural study.
PMID- 28490062
TI - Impact of frozen storage time on the volatile profile of wheat bread crumb.
AB - The freezing of wheat bread before aroma analyses is a common practice in order
to preserve loss of the volatile profile. However, the impact of the frozen
storage time on the aroma profile has not been studied. For this purpose, the
volatile profiles of wheat bread frozen for 1, 2 and 4weeks were analysed
employing solvent extraction and static headspace methoologies with GC/MS. The
results revealed that the freezing was effective to prevent the loss of volatiles
during the first week. However, after two weeks, there was an increase of
volatile compounds, probably generated by chemical reactions. Thus, a maximum of
one week of frozen storage was recommended when using the solvent extraction
methodology. When using the static headspace method, the samples should be
analysed on the same day as preparation, since the extraction was surprisingly
increased due to the starch retrogradation that occurred during freezing.
PMID- 28490063
TI - Characterisation of a thiamine diphosphate-dependent alpha-keto acid
decarboxylase from Proteus mirabilis JN458.
AB - Alpha-keto acid decarboxylases can convert keto acids to their corresponding
aldehydes, which are often volatile aroma compounds. The gene encoding alpha-keto
acid decarboxylase in Proteus mirabilis JN458 was cloned, and the enzyme
overexpressed in Escherichia coli BL21 (DE3), purified in high yield, and
characterised. The molecular weight is 62.291kDa by MALDI-TOF MS, and optimum
activity at pH 6.0 and 40-50 degrees C. The enzyme is a typical decarboxylase,
dependent on thiamine diphosphate and Mg2+ as cofactors. For the decarboxylation
reaction, the enzyme displayed a broad substrate range. Kinetic parameters were
determined using 4-methyl-2-oxopentanoic acid, phenyl pyruvate and 3-methyl-2
oxopentanoic acid as substrates. Km and kcat values for phenyl pyruvate were
0.62mM and 77.38s-1, respectively, and the kcat/Km value was 124.81mM-1s-1. The
enzyme properties suggest it may act effectively under cheese ripening
conditions.
PMID- 28490064
TI - Thymol nanoemulsions formed via spontaneous emulsification: Physical and
antimicrobial properties.
AB - In this work, we prepared various sub-micron thymol emulsions with high
hydrophilic-lipophilic balance (HLB) surfactants via spontaneous emulsification.
Emulsion properties, such as size, polydispersity and charge, were assessed for
each surfactant type and mass fraction. Emulsion stability was characterized by
monitoring droplet size following exposure to physical (centrifugation) and
thermal stressors (freeze, thaw cycling). Emulsions were subsequently screened
against several challenge pathogens to evaluate antimicrobial efficacy. Based on
these time-kill assays, exemplary formulations were further tested as sanitizing
washes on lettuce and blueberries inoculated with food-borne bacterial biofilms.
Antimicrobial data elucidate both surfactant and formulation specific antagonisms
between thymol and the emulsifying agents. However, the best emulsion
compositions were capable of reducing planktonic bacteria by >4 logs and biofilm
bacteria by 1.5-2.5 logs in 60 s. These results are comparable to the efficacy of
chlorine at ~50-200ppm. The experimental results have implications in emulsion
formulations involving thymol and other terpenoids.
PMID- 28490065
TI - Residue analysis of tetracyclines in milk by HPLC coupled with hollow fiber
membranes-based dynamic liquid-liquid micro-extraction.
AB - A novel hollow fiber membranes-based dynamic liquid-liquid micro-extraction (HF
DLLME) coupled with HPLC-UV detection has been developed for the residue analysis
of tetracyclines in milk samples without deproteinization and degreasing. The
influences of experimental parameters were investigated and optimized. The method
showed a good performance. The limits of detection (LOD) are in the range of 0.95
3.6MUg/L. The recoveries in spiked samples range from 92.38 to 107.3%. The
relative standard deviations (RSDs) are lower than 8.66%. The advantages of this
method are simple operation, high efficiency, absence of sample carryover and low
cost.
PMID- 28490066
TI - The physico-chemical alteration of lovastatin and enhanced antioxidant effect of
Bacillus subtilis fermented-red yeast rice product.
AB - Red yeast rice product (RYP) has been used as a food supplement because of its
lipid lowering, and in food additives as a natural colorant. Lovastatin of RYP is
a hypolipidemic commercial drug. To enhance the beneficial effects of RYP, we
performed a bioconversion with Bacillus subtilis. This B. subtilis-fermentation
process of RYP increased the ratio of the active open-hydroxyl acid form and the
prodrug lactone form of lovastatin, which is a potent cholesterol synthesis
inhibitor. 3(2H)-benzofuranone was newly produced in the fermented red yeast rice
product (FRYP) as analyzed by GC-MS. FRYP increased the free radical scavenging
activity compared with RYP. FRYP blocked xanthine oxidase (XO)-induced oxidative
cytotoxicity and inhibited the H2O2-induced intracellular ROS in cells. This is
the first study to illustrate that B. subtilis-fermented FRYP is useful for
facilitating the alteration in the physico-chemical property of lovastatin and
enhancing antioxidant activity, which may have greater pharmacological activity.
PMID- 28490067
TI - Comparison of nutritional quality and sensory acceptability of biscuits obtained
from native, fermented, and malted pearl millet (Pennisetum glaucum) flour.
AB - The effects of fermentation and malting on the proximate composition, mineral
content, amino acids and total phenolic content of pearl millet flour and
biscuits were studied. Consumer tests of the biscuits samples were also done
using two sets of panelists. The results showed that fermentation and malting
improved the crude fiber, crude protein, carbohydrate and energy values of the
pearl millet flour. For the biscuit samples, the fermented and malted biscuits
had higher moisture, crude protein, crude fiber and energy value with lower fat
and ash content as compared to the biscuits obtained from native flour.
Fermentation and malting were further observed to increase majority of the
essential and non-essential amino acids. Consumer tests among the different set
of panelists showed differences in the loading patterns as observed through
principal component analysis. In conclusion, this study shows that fermentation
and malting improves nutritional, health composition of pearl millet flour as
well as the sensorial acceptability of subsequent biscuits.
PMID- 28490068
TI - Micropollutants and chemical residues in organic and conventional meat.
AB - The chemical contamination levels of both conventional and organic meats were
assessed. The objective was to provide occurrence data in a context of chronic
exposure. Environmental contaminants (17 polychlorinated
dibenzodioxins/dibenzofurans, 18 polychlorinated biphenyls (PCBs), 3
hexabromocyclododecane (HBCD) isomers, 6 mycotoxins, 6 inorganic compounds)
together with chemical residues arising from production inputs (75
antimicrobials, 10 coccidiostats and 121 pesticides) have been selected as
relevant compounds. A dedicated sampling strategy, representative of the French
production allowed quantification of a large sample set (n=266) including both
conventional (n=139) and organic (n=127) raw meat from three animal species
(bovine, porcine, poultry). While contamination levels below regulatory limits
were measured in all the samples, significant differences were observed between
both species and types of farming. Several environmental contaminants (Dioxins,
PCBs, HBCD, Zn, Cu, Cd, Pb, As) were measured at significantly higher levels in
organic samples.
PMID- 28490069
TI - Study of the contribution of massoia lactone to the aroma of Merlot and Cabernet
Sauvignon musts and wines.
AB - Organic extracts of musts and red wines marked by dried fruit and cooked fruit
aromas were analyzed by gas chromatography coupled to olfactometry and mass
spectrometry. Thanks to this analytical approach we identified a fragrant lactone
corresponding to an odorant zone reminiscent of coconut and dried figs as 5,6
dihydro-6-pentyl-2H-pyran-2-one (C10 massoia lactone). Using chiral GC-GC-MS, we
show that only the (R)-C10 massoia lactone is found in musts and wines. Its
detection thresholds were 10ug/L and 11ug/L in must and wine model solution,
respectively. In Merlot and Cabernet Sauvignon musts marked by dried fruit
flavors from overripe grapes, its concentration reached 68ug/L. In contrast, in
wines marked by these flavors, it never exceeded 20ug/L. We show that (R)-C10
massoia lactone is reduced to (R)-delta-decalactone during alcoholic
fermentation. In addition, we underline the contribution of temperature during
the growing season on its level in old red wines.
PMID- 28490070
TI - Utilisation of immature wheat flour as an alternative flour with antioxidant
activity and consumer perception on its baked product.
AB - The purpose of this study was to investigate the utilisation of immature wheat
flour (IWF) as an alternative flour with antioxidant activity. Antioxidant
properties and phenolic acid compositions of IWF and IWF madeleine were compared
with those of commercial wheat flour (WF) and WF madeleine. Consumer perception
of madeleine was studied using a blind test followed by an informed test, which
provided information on antioxidant properties of flours. The bound ferulic acid
in IWF (5.54mg/100g) was seven times higher than that in WF (0.74mg/100g). Oxygen
radical absorbance capacity of IWF (34.47umol TE/g) and IWF madeleine (14.63umol
TE/g) were higher than those of WF. The results of blind test showed that
consumer acceptability and willingness to pay (WTP) of IWF madeleine were lower
than those of WF madeleine. However, about 25% of consumers preferred IWF
madeleine, implying small niche market for IWF as alternative flour.
PMID- 28490071
TI - Recovery of a bacteriocin-like inhibitory substance from Pediococcus acidilactici
Kp10 using surfactant precipitation.
AB - Bacteriocin is an important peptide which can be used as an anti-microbial agent
in food. However, simpler and more cost-effective purification methods need to be
developed compared to chromatography to enhance its commercial viability.
Surfactant precipitation was employed for the first time to purify bacteriocin
like inhibitory substance (BLIS) from a fermentation broth of Pediococcus
acidilactici Kp10, and the amount precipitated was investigated as a function of
anionic surfactant (AOT) concentration, and pH. Protein recovery from the
precipitate was accomplished using solvent extraction, and solvent type, NaCl
concentration, and ionic strength of the final solution were optimised. Optimal
conditions were; 1.05mM of AOT at pH 4 for precipitation, and acetone extraction
(with 1mM NaCl), which resulted in an 86.3% yield, and 53.8 purification factor.
This study highlighted the fact that surfactant precipitation can be used as a
primary recovery method for BLIS from a complex fermentation broth.
PMID- 28490072
TI - Evolution of free and bound volatile aroma compounds and phenols during
fermentation of Muscat blanc grape juice with and without skins.
AB - Recently, various technologies which utilise fermentation with skins have been
developed for obtaining distinct white wines. This study first reports the
dynamic changes of volatiles and phenols that occur during skin fermentation in
white winemaking. Volatiles were analysed by solid-phase extraction (SPE), solid
phase microextraction (SPME) and gas chromatography (GC), and phenols by ultra
performance liquid chromatography (UPLC), both with mass spectrometric detection.
Monoterpenols increased during the first 3days of skin fermentation, after which
certain glycosides decreased, but were higher than in control. The presence of
skins reduced ho-trienol, beta-damascenone, acids and esters. After a 1-3days lag
phase, skin fermentation caused a constant increase of most phenols. It was
estimated that skin fermentation up to 1-3days might be beneficial for
monoterpenol varietal aroma, which should be re-evaluated through further
studies. Longer durations promoted phenol extraction more strongly, which is
possibly suitable for obtaining more distinct wines or blending components.
PMID- 28490073
TI - The use of high hydrostatic pressure to generate folate-enriched extracts from
the granule fraction of hen's egg yolk.
AB - The present work characterized the effects of pre-treatments on the protein
profile and microstructure of granule fractions from egg yolk. The granule
microstructure was studied using confocal laser scanning microscopy (CLSM). The
protein profiles of the pre-treated granule and the corresponding plasma fraction
were studied using 2D gel electrophoresis techniques. Further, we explored the
potential for using high hydrostatic pressure (HHP) to promote disintegration of
the granule structure. The CLSM micrographs provided evidence of the substantial
disintegration of granules due to HHP (600MPa/5min). Results from high
performance liquid chromatography (HPLC) analysis indicated high concentrations
of folate in the plasma fractions (230ug/g dry matter) separated from the HHP
treated granule. Sodium Dodecyl Sulphate-Polyacrylamide Gel Electrophoresis (SDS
PAGE) analysis revealed the localization of phosvitin in the plasma fraction,
which correlated with higher folate concentrations. The results demonstrate that
phosvitin and folate were stable under the HHP conditions applied in this study.
These findings provide evidence of a putative interaction between phosvitin and
folate, and offer an improved model for the structure of granule.
PMID- 28490074
TI - Determination of heat-set gelation capacity of a quinoa protein isolate
(Chenopodium quinoa) by dynamic oscillatory rheological analysis.
AB - This work aimed to study the influence of pH (3.5 and 7.0) and CaCl2 and MgCl2
addition on heat-set gelation of a quinoa protein isolate at 10% and 15% (w/w).
The protein isolate obtained was composed mainly of 11S globulin as was observed
by electrophoresis and mass spectrometry analysis. Heat-set gelation occurred at
both pH values studied. Nevertheless, the gels formed at pH 3.5 were more
viscoelastic and denser than those formed at pH 7.0, that was coarser and
presented syneresis. The CaCl2 and MgCl2 addition increased the gel strength
during rheological analysis at pH 3.5, possibly due to the formation of fiber
like connections in the gel network. At pH 7.0, the divalent salts resulted in
weaker gels formed by agglomerates, suggesting a neutralization of the protein
surface charges. The differences in quinoa protein gelation were attributed to
solubility, and the flexibility of proteins secondary structure at the pH
studied.
PMID- 28490075
TI - Development of a near-infrared spectroscopy method (NIRS) for fast analysis of
total, indolic, aliphatic and individual glucosinolates in new bred open
pollinating genotypes of broccoli (Brassica oleracea convar. botrytis var.
italica).
AB - This study describes the development of near-infrared spectroscopy (NIRS)
calibration to determine individual and total glucosinolates (GSLs) content of 12
new-bred open-pollinating genotypes of broccoli (Brassica oleracea convar.
botrytis var. italica). Six individual GSLs were identified using high
performance-liquid chromatography (HPLC). The NIRS calibration was established
based on modified partial least squares regression with reference values of HPLC.
The calibration was analyzed using coefficient of determination in prediction
(R2) and ratio of preference of determination (RPD). Large variation occurred in
the calibrations, R2 and RPD due to the variability of the samples. Derived
calibrations for total-GSLs, aliphatic-GSLs, glucoraphanin and 4
methoxyglucobrassicin were quantitative with a high accuracy (RPD=1.36, 1.65,
1.63, 1.11) while, for indole-GSLs, glucosinigrin, glucoiberin, glucobrassicin
and 1-methoxyglucobrassicin were more qualitative (RPD=0.95, 0.62, 0.67, 0.81,
0.56). Overall, the results indicated NIRS has a good potential to determine
different GSLs in a large sample pool of broccoli quantitatively and
qualitatively.
PMID- 28490076
TI - Lipase mediated synthesis of rutin fatty ester: Study of its process parameters
and solvent polarity.
AB - Lipophilization of antioxidants is recognized as an effective strategy to enhance
solubility and thus effectiveness in lipid based food. In this study, an effort
was made to optimize rutin fatty ester synthesis in two different solvent systems
to understand the influence of reaction system hydrophobicity on the optimum
conditions using immobilised Candida antartica lipase. Under unoptimized
conditions, 52.14% and 13.02% conversion was achieved in acetone and tert-butanol
solvent systems, respectively. Among all the process parameters, water activity
of the system was found to show highest influence on the conversion in each
reaction system. In the presence of molecular sieves, the ester production
increased to 62.9% in tert-butanol system, unlike acetone system. Under optimal
conditions, conversion increased to 60.74% and 65.73% in acetone and tert-butanol
system, respectively. This study shows, maintaining optimal water activity is
crucial in reaction systems having polar solvents compared to more non-polar
solvents.
PMID- 28490077
TI - Characterization of Satsuma mandarin (Citrus unshiu Marc.) nectar-to-honey
transformation pathway using FTIR-ATR spectroscopy.
AB - Samples of Satsuma mandarin (Citrus unshiu Marc.) nectar, honey sac content and
honey were analyzed by FTIR-ATR spectroscopy and reference methods. The spectral
analysis allowed detection of the major chemical constituents in C. unshiu nectar
to-honey transformation pathway thus providing information on the intensity and
location of the compositional changes occurring during this process. The
preliminary results showed that in average more than one-third of sugar-related
nectar-to-honey conversion takes place directly in the honey sac; the average
sugar content (w/w) was 17.93% (nectar), 47.03% (honey sac) and 79.63% (honey).
FTIR-ATR results showed great spectral similarity of analyzed honey samples and
small degree variations in both sugar and water content in nectar samples. The
spectral data revealed distinctive differences in the chemical composition of
individual honey sac contents with the most intensive and complex absorption
envelope in the spectral region between 1175 and 950cm-1 (glucose, fructose and
sucrose absorption bands).
PMID- 28490078
TI - Characterization of phenolic compounds in chia (Salvia hispanica L.) seeds, fiber
flour and oil.
AB - The consumption of chia seeds products has increased recently and it has been
suggested that the inclusion of this functional food in a daily human diet could
contribute to improve consumers' health. However, a better knowledge about the
composition of these products is mandatory. In this work, the phenolic compounds
from commercial samples of chia seed, fiber flour and oil were extracted using an
ultrasound-assisted methodology and were separated and identified by high
performance liquid chromatography coupled to a mass spectrometer. Methanol:water
extracts were prepared and submitted to an acidic hydrolysis. Crude and
hydrolyzed extracts were analyzed and phenolic compounds found were mainly
caffeic acid and danshensu and its derivatives, such as rosmarinic and
salvianolic acids. TPC was higher in the hydrolyzed extracts. These results
supply new information about the main phenolic compounds presents in chia, which
are important dietary sources of natural antioxidants for prevention of diseases
caused by oxidative stress.
PMID- 28490079
TI - Influence of osmotic dehydration pre-treatment and combined drying method on
physico-chemical and sensory properties of pomegranate arils, cultivar Mollar de
Elche.
AB - "Mollar de Elche" is the most popular Spanish pomegranate cultivar (intense
sweetness and easy-to-chew arils); however, arils have pale pink colour and flat
sensory profile. "Mollar the Elche" arils first underwent an osmotic dehydration
pre-treatment (OD) with concentrated juices: (i) chokeberry, (ii) apple, and/or
(iii) pomegranate cultivar "Wonderful", to improve their antioxidant capacity,
colour, and sensory profile complexity, and later the arils were dried by a
combined method (convective pre-drying+vacuum microwave finish drying). The use
of OD provided dried arils with characteristic sweetness, and improved colour and
aromatic complexity. The recommended OD methods were those using (i) pomegranate,
and (ii) pomegranate with chokeberry juices; they improved the total anthocyanin
content (mean of 368mgkg-1), red colour (a* coordinate 15.6), and antioxidant
capacity (e.g. ABTS mean of 5.7mmolTrolox100g-1). However, further research is
still needed because freeze-dried arils had the highest anthocyanin content.
PMID- 28490080
TI - Utilization of watermelon pulp for lycopene extraction by response surface
methodology.
AB - Lycopene extraction was optimized from watermelon pulp using response surface
methodology using independent variables:solvent/meal ratio (4:1-12:1v/w), number
of extractions (1-5), temperature (20-60 degrees C) and extraction time (4
20min). Watermelon pulp had 59.95mglycopene/100g on fresh weight basis. The
experimental values of lycopene with selected combinations of independent
variables were 8.20-59.17mg/100g on fresh weight basis. The second order model
obtained revealed a coefficient of determination (R2) of 0.986, the standard
error of 0.04, the root mean square error of 0.02 and a scattered plot between
experimental and predicted values. The optimum solvent/meal ratio, number of
extractions, temperature and extraction time were 10:1v/w, four, 50 degrees C and
16min respectively. The optimum conditions of lycopene extraction were confirmed
experimentally.
PMID- 28490081
TI - Qualitative and quantitative analysis of milk for the detection of adulteration
by Laser Induced Breakdown Spectroscopy (LIBS).
AB - The present work focuses on the development of a fast and cost effective method
based on Laser Induced Breakdown Spectroscopy (LIBS) to the quality control,
traceability and detection of adulteration in milk. Two adulteration cases have
been studied; a qualitative analysis for the discrimination between different
milk blends and quantification of melamine in adulterated toddler milk powder.
Principal Component Analysis (PCA) and neural networks (NN) have been used to
analyze LIBS spectra obtaining a correct classification rate of 98% with a 100%
of robustness. For the quantification of melamine, two methodologies have been
developed; univariate analysis using CN emission band and multivariate
calibration NN model obtaining correlation coefficient (R2) values of 0.982 and
0.999 respectively. The results of the use of LIBS technique coupled with
chemometric analysis are discussed in terms of its potential use in the food
industry to perform the quality control of this dairy product.
PMID- 28490082
TI - Spasmolytic, antimicrobial and cytotoxic activities of 5-phenylpentyl
isothiocyanate, a new glucosinolate autolysis product from horseradish (Armoracia
rusticana P. Gaertn., B. Mey. & Scherb., Brassicaceae).
AB - Detailed analyses of horseradish autolysates led to the identification of a new
natural product, 5-phenylpentyl isothiocyanate (PhPeITC). The structural
assignment was corroborated by synthesis, and the identity unequivocally
established by spectral means. The occurrence of PhPeITC is the first direct
proof of the existence of a 5-phenylpentyl glucosinolate in the aerial parts of
this species as one of the possible "mustard oil" precursors. To verify its
possible contribution to the horseradish functional food status, horseradish
above- and underground autolysates, together with five omega-phenylalkyl
isothiocyanates were tested for their spasmolytic, cytotoxic and antimicrobial
activities. Specifically, the cytotoxic effect on Caco-2, HeLa (cancer) and MDCK
(non-cancer) cell lines was established. Additionally, the five tested ITCs
exerted significant spasmolytic activity (on rat distal colon), with PhPeITC
being almost 100 times more potent than papaverine. A non-selective antimicrobial
activity of all ITCs was revealed in the case of 6 bacterial and 2 fungal
strains.
PMID- 28490083
TI - Combining hydrothermal pretreatment with enzymes de-pectinates and exposes the
innermost xyloglucan-rich hemicellulose layers of wine grape pomace.
AB - Chardonnay grape pomace was treated with pressurized heat followed by enzymatic
hydrolysis, with commercial or pure enzymes, in buffered conditions. The pomace
was unfermented as commonly found for white winemaking wastes and treatments
aimed to simulate biovalorization processing. Cell wall profiling techniques
showed that the pretreatment led to depectination of the outer layers thereby
exposing xylan polymers and increasing the extractability of arabinans,
galactans, arabinogalactan proteins and mannans. This higher extractability is
believed to be linked with partial degradation and opening-up of cell wall
networks. Pectinase-rich enzyme preparations were presumably able to access the
inner rhamnogalacturonan I dominant coating layers due to the hydrothermal
pretreatment. Patterns of epitope abundance and the sequential release of cell
wall polymers with specific combinations of enzymes led to a working model of the
hitherto, poorly understood innermost xyloglucan-rich hemicellulose layers of
unfermented grape pomace.
PMID- 28490084
TI - An integrated strategy combining DNA walking and NGS to detect GMOs.
AB - Recently, we developed a DNA walking system for the detection and
characterization of a broad spectrum of GMOs in routine analysis of food/feed
matrices. Here, we present a new version with improved throughput and sensitivity
by coupling the DNA walking system to Pacific Bioscience(r) Next-generation
sequencing technology. The performance of the new strategy was thoroughly
assessed through several assays. First, we tested its detection and
identification capability on grains with high or low GMO content. Second, the
potential impacts of food processing were investigated using rice noodle samples.
Finally, GMO mixtures and a real-life sample were analyzed to illustrate the
applicability of the proposed strategy in routine GMO analysis. In all tested
samples, the presence of multiple GMOs was unambiguously proven by the
characterization of transgene flanking regions and the combinations of elements
that are typical for transgene constructs.
PMID- 28490085
TI - Cellulose nanomaterials emulsion coatings for controlling physiological activity,
modifying surface morphology, and enhancing storability of postharvest bananas
(Musa acuminate).
AB - Cellulose nanomaterials (CNs)-incorporated emulsion coatings with improved
moisture barrier, wettability and surface adhesion onto fruit surfaces were
developed for controlling postharvest physiological activity and enhancing
storability of bananas during ambient storage. Cellulose nanofiber (CNF)-based
emulsion coating (CNFC: 0.3% CNF/1% oleic acid/1% sucrose ester fatty acid (w/w
wet base)) had low contact angle, high spread coefficient onto banana surfaces,
and lower surface tension (ST, 25.4mN/m) than the critical ST (35.2mN/m) of
banana peels, and exhibited good wettability onto banana surfaces. CNFC coating
delayed the ethylene biosynthesis pathway and reduced ethylene and CO2
production, thus delaying fruit ripening. As the result, CNFC coating minimized
chlorophyll degradation, weight loss, and firmness of bananas while ensuring the
properly fruit ripening during 10d of ambient storage. This study demonstrated
the effectiveness of CNF based emulsion coatings for improving the storability of
postharvest bananas.
PMID- 28490086
TI - Molecular protocol for authentication of snappers (Lutjanidae-Perciformes) based
on multiplex PCR.
AB - Fraud involving fish products is regularly reported and investigated using
genetic methods. However, no such approach has been applied to snappers, despite
the commercial relevance of these fish. This study proposes an authentication
protocol with multiplex PCR for three species of snappers (Lutjanus purpureus, L.
synagris, and Ocyurus chrysurus). The protocol yielded a distinct triple-banding
pattern for L. purpureus, whereas L. synagris and O. chrysurus showed a double
banding pattern of different sizes, thereby allowing differentiation of the three
species. The protocol was validated using fillets labeled as snapper or "Pargo"
in Brazil, previously identified using DNA sequencing, amongst which substitution
with Rhomboplites aurorubens was detected. When subjected to the new protocol,
banding characteristic of L. purpureus were detected whilst R. aurorubens
generated only the control band. Our study provides a practical tool for
investigating substitutions and might assist in quality control and increase food
safety for consumers.
PMID- 28490087
TI - Use of FT-IR, FT-Raman and thermal analysis to evaluate the gel formation of
curdlan produced by Agrobacterium sp. IFO 13140 and determination of its
rheological properties with food applicability.
AB - Curdlan is a linear polysaccharide composed of glucose units joined by beta-(1,3)
bonds that possesses unique gelation properties. This study aimed to characterize
the structure and evaluate the gelling properties of curdlan produced by
Agrobacterium sp. IFO 13140 and its gels, as well as apply it in food. FT-Raman
analysis highlighted the structural changes that occurred during the formation of
gels, with variations related to the hydrogen bonds and hydrophobic interactions,
which occur with the formation of the low-set and high-set gels, respectively.
Rheological analysis showed that the pre-gelled commercial curdlan and the
curdlan produced by Agrobacterium sp. IFO 13140 differed in terms of gelation
properties, which depends of the degree of polymerization of the polysaccharide,
but when applied to pasta products, both improved the texture parameters. The
curdlan gels were found to have great potential as gelling agents to improve
texture, water retention capacity and stability of food products.
PMID- 28490088
TI - Antioxidant activities of aqueous extract from Stevia rebaudiana stem waste to
inhibit fish oil oxidation and identification of its phenolic compounds.
AB - We investigated the potential for exploiting Stevia rebaudiana stem (SRS) waste
as a source of edible plant-based antioxidants finding for the first time that
the hot water extract of SRS had significantly higher antioxidant activity
against fish oil oxidation than that of the leaf, despite SRS extract having
lower total phenolic content, DPPH radical scavenging activity and ORAC values.
To locate the major antioxidant ingredients, SRS extract was fractionated using
liquid chromatography. Five phenolic compounds (primary antioxidant components in
activity-containing fractions) were identified by NMR and HR-ESI-MS: vanillic
acid 4-O-beta-d-glucopyranoside (1), protocatechuic acid (2), caffeic acid (3),
chlorogenic acid (4) and cryptochlorogenic acid (5). Further analysis showed
that, among compounds 2-5, protocatechuic acid had the highest capacity to
inhibit peroxides formation, but exhibited the lowest antioxidant activities in
DPPH and ORAC assays. These results indicate that SRS waste can be used as strong
natural antioxidant materials in the food industry.
PMID- 28490089
TI - Molecular structure, stability and cytotoxicity of natural green colorants
produced from Centella asiatica L. leaves treated by steaming and metal
complexations.
AB - Stability of extracts from Centella asiatica L. leaves treated by steaming and
metal-chlorophylls complexations against combined acid-heat was compared with
that from untreated leaves and synthetic colorant. Formation of metal
chlorophylls complexes was confirmed by FTIR spectroscopy. Molecular structure
changes during stability test and cytotoxicity of the extracts against Vero cells
were evaluated. Utilization of the extracts as colorant was also assessed in
selected beverage ingredient and food. Copper-chlorophylls extracts exhibited
similar green hue to those from untreated and steamed leaves, while zinc
chlorophylls extracts exhibited yellow-green color. Metal-chlorophylls extracts
possessed higher stability against combined acid-heat than those from untreated
and steamed leaves. Use of metal-chlorophylls extracts in beverage ingredient led
to increased hue value due to their structural rearrangement, which was confirmed
by changes in Q band of VIS spectra. Cytotoxicity of zinc- and copper
chlorophylls extracts was slightly different and higher than those of extracts
from untreated/steamed leaves and synthetic colorant.
PMID- 28490090
TI - Effects of pan cooking on micropollutants in meat.
AB - This work presents the effects of pan cooking on PCBs, PCDD/Fs, pesticides and
trace elements in meat from a risk assessment perspective. Three different
realistic cooking intensities were studied. A GC*GC-TOF/MS method was set up for
the multiresidue analysis of 189 PCBs, 17 PCDD/Fs and 16 pesticides whereas Cd,
As, Pb and Hg were assayed by ICP-MS. In terms of quantity, average PCB losses
after cooking were 18+/-5% for rare, 30+/-3% for medium, and 48+/-2% for well
done meat. In contrast, average PCDD/F losses were not significant. For
pesticides, no loss occurred for aldrin, lindane, DDE or DDD, whereas losses
exceeding 80% were found for dieldrin, sulfotep or phorate. Losses close to the
margin of error were observed for trace elements. These results are discussed in
light of the physicochemical properties of the micropollutants as well as of
water and fat losses into cooking juice.
PMID- 28490091
TI - Physico-chemical characterization of dairy gel obtained by a proteolytic extract
from Calotropis procera - A comparison with chymosin.
AB - Chymosin is the major enzyme used in cheesemaking but latex enzymes are also
used. The aim of this work was to characterize the composition and the structure
of dairy gel obtained by an extract of Calotropis procera leaves in comparison
with those obtained by chymosin. The biochemical and mineral compositions of the
curds and the cheese yields obtained by using Calotropis procera extract or
chymosin were relatively similar. Quantitative and qualitative evaluations of
proteolysis after milk coagulation, determined by the non-protein nitrogen
content and chromatography coupled to mass spectrometry, indicated that
Calotropis procera extract was more proteolytic than chymosin and that kappa
casein was proteolyzed. The main consequence of proteolysis by Calotropis procera
extract or chymosin was the formation of a similar and regular network with the
presence of aggregates of casein micelles. These results support that Calotropis
procera extract can be used as effective coagulant in cheesemaking.
PMID- 28490092
TI - The contribution of wine-derived monoterpene glycosides to retronasal odour
during tasting.
AB - This study investigated the sensory significance of monoterpene glycosides during
tasting, by retronasal perception of odorant aglycones released in-mouth.
Monoterpene glycosides were isolated from Gewurztraminer and Riesling juices and
wines, chemically characterised and studied using sensory time-intensity
methodology, together with a synthesised monoterpene glucoside. When assessed in
model wine at five times wine-like concentration, Gewurztraminer glycosides and
geranyl glucoside gave significant fruity flavour, although at wine-like
concentrations, or in the presence of wine volatiles, the effect was not
significant. Gewurztraminer glycosides, geranyl glucoside and guaiacyl glucoside
were investigated using a sensory panel (n=39), revealing large inter-individual
variability, with 77% of panellists responding to at least one glycoside. The
study showed for the first time that grape-derived glycosides can contribute
perceptible fruity flavour, providing a means of enhancing flavour in wines, and
confirms the results of previous studies that the effect is highly variable
across individuals.
PMID- 28490093
TI - Effect of heat, pH, ultrasonication and ethanol on the denaturation of whey
protein isolate using a newly developed approach in the analysis of difference-UV
spectra.
AB - A newly developed method of analysis of difference-UV spectra was successfully
implemented in the study of the effect of heat, pH, ultrasonication and ethanol
on the denaturation of whey protein isolate. It was found that whey proteins
exhibit their highest stability against heat denaturation at pH 3.75. At very low
pH values, i.e. 2.5, they exhibited considerable cold denaturation, while after
heating at this pH value, the supplementary heat denaturation rate was lower
compared to that at neutral pH. The highest heat denaturation rates were observed
at pH values higher than neutral. High power sonication on whey proteins,
previously heated at 90 degrees C for 30min, resulted in a rather small reduction
of the fraction of the heat denatured protein aggregates. Finally, when ethanol
was used as a cosolvent in the concentration range 20-50%, a sharp increase in
the degree of denaturation, compared to the native protein solution, was
observed.
PMID- 28490094
TI - Development of monoclonal antibody-based ELISA for the quantification of orange
allergen Cit s 2 in fresh and processed oranges.
AB - The aim of this study was to develop a monoclonal antibody (mAb)-based enzyme
linked immunosorbent assay (ELISA) for the quantification of a major allergen
(Cit s 2) in fresh and processed oranges. Purified recombinant Cit s 2 (rCit s 2)
small ubiquitin-like modifier (SUMO) was used for the production of mAbs. In the
optimized ELISA, the recovery of rCit s 2 from Navel oranges or orange juice was
107-132%, and the intra- and inter-assay coefficients of variation were 3.1-8.8%
and 4.4-11%, respectively. The Cit s 2 content in fresh oranges was determined to
be 1,800+/-430ng/g, while this content was much lower in the processed foods. The
developed ELISA demonstrated high reproducibility, sensitivity, and accuracy, and
this assay may help individuals with orange allergy by determining Cit s 2
quantities in food products and controlling their Cit s 2 intake.
PMID- 28490095
TI - A cold-induced phytosulfokine peptide is related to the improvement of loquat
fruit chilling tolerance.
AB - A novel peptidomics approach was used to discover cold-induced peptides in loquat
fruit. Twenty unique peptides derived from 18 proproteins were identified, and
they were involved in sugar signalling, protein metabolism and stress response.
The quantitative analysis revealed 7 peptides with more than 2-fold upregulation,
especially a 4.96-fold increase detected in the phytosulfokine (PSK) peptide. To
further evaluate effects of PSK1 on fruit chilling tolerance, weight loss,
firmness and internal browning were investigated in PSK1-treated loquat fruit at
0 degrees C. By contrast, these chilling injury symptoms were effectively reduced
by PSK1. PSK1 markedly delayed decreases of ATP content and energy charge. The
PSK1-treated fruit exhibited significantly lower activities of cell-wall
degrading enzymes and transcripts of genes related to lignin synthesis. Our
results demonstrated that PSK1 improves chilling tolerance of loquat fruit by
maintaining high energy status and cell integrity. Peptidomics analysis provides
a promising tool to discover some key peptides.
PMID- 28490096
TI - Effects of high-speed homogenization and high-pressure homogenization on
structure of tomato residue fibers.
AB - Tomato residue fibers obtained after derosination and deproteinization were
processed by high-speed homogenization (HSH) and high-pressure homogenization
(HPH), and their effects on fiber structure was investigated, respectively.
Characterizations including particle size distribution, SEM, TEM and XRD were
performed. HSH could break raw fibers to small particles of around 60MUm, while
HPH could reshape fibers to build network structure. Microfibrils were released
and their nanostructure consisting of elementary fibrils was observed by TEM. XRD
patterns indicated both HSH and HPH could hardly alter the nanostructure of the
fibers. Physicochemical properties including expansibility, WHC and OHC were
determined. Both HSH and HPH could increase the soluble fiber content by about
8%, but HSH-HPH combined processing did not show better result. Acid (4mol/L HCl)
was used in replacement of water medium and the acidic degradation of fibers
could be promoted by high speed shearing or high pressure processing.
PMID- 28490098
TI - Unravelling important odorants in horseradish (Armoracia rusticana).
AB - Horseradish (Armoracia rusticana) is a plant well known for its roots' spicy
aroma. The present study investigates the main aroma constituents of horseradish
roots in general by analysing the aroma profiles of six different horseradish
varieties, with one variety grown in two different soils. Odorants were
characterised by means of gas chromatography-olfactometry and identified via
their mass spectra, retention indices on two columns with different polarity, and
their characteristic odour. A series of new aroma compounds from different
substance groups were identified that have hitherto not been described in
horseradish. Moreover, several of these constituents were successfully shown to
exhibit high odour potency, alongside a high potential to influence the overall
aroma of horseradish roots, like (3S,3aS,7aR)-wine lactone and 3-isopropyl-2
methoxypyrazine.
PMID- 28490097
TI - Influence of l-pyroglutamic acid on the color formation process of non-enzymatic
browning reactions.
AB - Heating aqueous d-glucose model reactions with l-glutamine and l-alanine yielded
similar colored solutions. However, size-exclusion chromatography (SEC) revealed
that both non-enzymatic browning reactions proceeded differently. Due to a fast
occurring cyclization of l-glutamine to pyroglutamic acid, the typical amino
carbonyl reaction was slowed down. However, l-glutamine and l-alanine model
reactions showed the same browning index. Closer investigations could prove that
l-pyroglutamic acid was able to influence non-enzymatic browning reactions. SEC
analyses of d-glucose model reactions with and without l-pyroglutamic acid
revealed an increase of low molecular colored compounds in the presence of l
pyroglutamic acid. Polarimetric measurements showed a doubling of d-glucose
mutarotation velocity and HPLC analyses of d-fructose formation during thermal
treatment indicated a tripling of aldose-ketose transformation in the presence of
l-pyroglutamic acid, which are signs of a faster proceeding non-enzymatic
browning process. 2-Pyrrolidone showed no such behavior, thus the additional
carboxylic group should be responsible for the observed effects.
PMID- 28490099
TI - Phenolic profiles and metal ions analyses of pulp and peel of fruits and seeds of
quince (Cydonia oblonga Mill.).
AB - Six hydroxycinnamic acids were identified and determined quantitatively in
methanol and acetone extracts from quince peel and pulp, namely 3-O
caffeoylquinic acid (3-CQA), 4-p-coumaroylquinic acid (HC1), 4-O-caffeoylquinic
acid (4-CQA), 5-O-caffeoylquinic acid (5-CQA), derivative of p-coumaroylquinic
acid (HC2) and 3,5-dicaffeoylquinic acid (3,5-diCQA). The most abundant
hydroxycinnamic acid was 5-CQA (neochlorogenic acid) with 259.12-481.4mg/kgf.w.
in peel and 97.33-217.36mg/kg in quince pulp. Six flavonols were determined in
the extracts from quince, quercetin-3-galactoside (Q-Ga), quercetin-3-rutinoside
(Q-Ru), quercetin-3-glucoside (Q-Glu), kaempferol-3-rutinoside (K-Ru), kaempferol
3-glucoside (K-Glu) and derivative of quercetin produced in the reaction between
quercetin-glucoside and p-coumaric acid (Q-Glu-p-CouA). Elemental analysis of
quince seeds has not been performed previously. Also, using principal component
and cluster analyses, we determined a strong negative relationship between total
phenols and flavonoids, and Ni and Pb, specifically higher concentrations of
these compounds were associated with lower concentrations of these metals.
PMID- 28490100
TI - Plasma modification of starch.
AB - Plasma is a medium of unbound negative and positive particles with the overall
electrical charge being roughly zero. Non-thermal plasma processing is an
emerging green technology with great potential to improve the quality and
microbial safety of various food materials. Starch is a major component of many
food products and is an important ingredient for food and other industries. There
has been increasing interest in utilizing plasma to modify the functionalities of
starch through interactions with reactive species. This mini-review summarises
the impact of plasma on composition, chemical and granular structures,
physicochemical properties, and uses of starch. Structure-function relationships
of starch components as affected by plasma modifications are discussed. Effect of
plasma on the properties of wheat flour, which is a typical example of starch
based complex food systems, is also reviewed. Future research directions on how
to better utilise plasma to improve the functionalities of starch are suggested.
PMID- 28490101
TI - Feasibility of discrimination of dairy creams and cream-like analogues using
Raman spectroscopy and chemometric analysis.
AB - Dairy cream and its analogues with sunflower oil, coconut oil and palm oil in
different milk fat/vegetable fat ratios were prepared and analysed using Raman
spectroscopy. The linear discriminant analysis was conducted in order to classify
the samples. Samples were well separated and displayed distinguishing linear
arrangement along the principal component that expressed the variation in lipid
unsaturation. Good separation of sunflower oil and milk fat samples was obtained
in contrast to the samples with coconut and palm oil, where the substantial
overlapping occurred. The method permitted classifying of the samples in terms of
the type of fat used. Calibrated model was extremely sensitive (100%) for dairy
cream. The results indicated that it is possible to consider the Raman
spectroscopy coupled with chemometric analysis as a rapid way for the detection
of dairy cream adulteration with sunflower, coconut and palm oils.
PMID- 28490102
TI - Effect of grape juice press fractioning on polysaccharide and oligosaccharide
compositions of Pinot meunier and Chardonnay Champagne base wines.
AB - Press fractioning is an important step in the production of sparkling base wines
to segregate the grape juices with different qualities. Grape juice fractions
were collected during the pressing cycle at industrial and laboratory scales. The
Pinot meunier and Chardonnay Champagne base wines obtained from the free-run
juice and the squeezed juices exhibited strong differences from the beginning to
the last step of pressing cycle for numerous enological parameters. Significant
changes in polysaccharide (PS) and oligosaccharide (OS) base wine composition and
concentration were found as the pressing cycle progressed. During the pressing
cycle, the total PS concentration decreased by 31% (from 244 to 167mg/L) and 32%
(from 201 to 136mg/L) in the Pinot meunier and Chardonnay wines respectively. The
wine OS amounts varied between 97 and 139mg/L. The polysaccharide rich in
arabinose and galactose (39-54%) and mannoproteins (38-55%) were the major PS in
the base wines.
PMID- 28490103
TI - Speciation analysis of organoarsenic compounds in livestock feed by microwave
assisted extraction and high performance liquid chromatography coupled to atomic
fluorescence spectrometry.
AB - The development of a new method to determine the presence of the organoarsenic
additives p-arsanilic acid (ASA), roxarsone (ROX) and nitarsone (NIT) in
livestock feeds by high performance liquid chromatography coupled to ultraviolet
oxidation hydride generation atomic fluorescence spectrometry (HPLC-UV/HG-AFS)
after microwave assisted extraction (MAE) was proposed. Chromatographic
separation was achieved on a C18 column with 2% acetic acid/methanol (96:4, v/v)
as the mobile phase. The limits of detection (LODs) were 0.13, 0.09 and 0.08mgL
1, and the limits of quantification (LOQs) were 0.44, 0.30 and 0.28mgL-1. The
relative standard deviations (RSDs) for ASA, ROX and NIT determined from five
measurements of the mixed calibration standard were 3.3, 5.3, and 5.4%,
respectively. MAE extraction of phenylated arsenic compounds using 1.5M H3PO4 at
120 degrees C for 45min allowed for maximum recoveries (%) of total arsenic (As)
and organoarsenic species, with no degradation of these compounds. The extraction
of total As was approximately 97%, and the As species recoveries were between
95.2 and 97.0%. The results of the analysis were validated using mass balance by
comparing the sum of extracted As with the total concentration of As in the
corresponding samples. The method was successfully applied to determine the
presence of these compounds in feed samples. ASA was the only As species detected
in chicken feed samples, with a concentration between 0.72 and 12.91mgkg-1.
PMID- 28490104
TI - First approach to assess the bioaccessibility of bisphenol A in canned seafood.
AB - Human health risks due to bisphenol A (BPA) exposure through canned food
consumption are an emerging safety concern worldwide. In this study, an in vitro
digestion model was used to simulate human digestion and evaluate BPA
bioaccessibility in canned seafood for the first time. BPA contents of canned
tuna and sardine samples and their bioaccessible and non-bioaccessible fractions
were determined by gas chromatography coupled to mass spectrometry (GC-MS). The
21 samples of canned tuna and sardines, all from the same producer but with
different kind of sauces, showed BPA levels ranging from <1ugkg-1 (limit of
quantification, LOQ) to 62ugkg-1, with variable results within and between sample
groups. BPA bioaccessibility was evaluated in six positive samples, with values
ranging from 80 to 99%. The results suggest that BPA bioaccessibility was
slightly lower in samples with higher lipid content.
PMID- 28490105
TI - A novel technology for the rapid, selective, magnetic removal of pathogenesis
related proteins from wines.
AB - Haze formation is a significant problem for the wine industry. A novel technology
for the rapid, selective, magnetic removal of pathogenesis-related proteins from
wine was developed. The pathogenesis-related proteins in nine different white
wines were selectively captured and removed by acrylic acid plasma-coated
magnetic nanoparticles. Treated white wines were analyzed for protein and
phenolic content to assess the performance of the functionalized magnetic
nanoparticles. The analysis showed that the acrylic acid coated magnetic
nanoparticles effectively removed proteins and did not significantly change the
phenolic composition of the wines. This new technology may become an alternative
to conventional bentonite treatment which has economic and sensory impacts in the
wine production process. Furthermore, such rapid separation technology for the
binding and removal of proteins could benefit other areas such as diagnostics,
water treatment, biotechnology and therapeutics.
PMID- 28490106
TI - Inactivation of soybean trypsin inhibitor by dielectric-barrier discharge (DBD)
plasma.
AB - Soybean trypsin inhibitor (STI) is considered as one of the most important anti
nutritional factors in soybeans. The objective of this study was to investigate
the impacts and underling mechanisms of dielectric-barrier discharge (DBD) plasma
on STI activities. The results shown that DBD plasma treatment significantly
induced the inactivation of STI in soymilk and Kunitz-type trypsin inhibitor from
soybean (SKTI) in a model system. After exposure to DBD plasma at 51.4W for
21min, the STI activities of soymilk were reduced by 86.1%. Affter being treated
by DBD plasma, the intrinsic fluorescence and surface hydrophobicity of SKTI were
significantly decreased, while the sulfhydryl contents were increased. It is
assumed that DBD plasma-induced conformational changes and oxidative modification
might contribute to the inactivation of SKTI. In summary, DBD plasma technology
is a potential alternative to heat treatment for the inactivation of anti
nutritional substances in food legumes.
PMID- 28490107
TI - Simultaneous estimation of scavenging capacities of peach extract for multiple
reactive oxygen species by fluorescence fingerprint method.
AB - In this study, the potential of using fluorescence fingerprint, also known as
fluorescence excitation-emission matrix, for estimating the scavenging capacity
of peach extract on reactive oxygen species (ROS) was investigated. Samples from
each of the five cultivars (Asama Hakuto, Hakuho, Kawanakajima Hakuto, Natsukko
and Ougonto) were freeze-dried and crushed. The scavenging capacities of peach
extracts for the target ROS (hydroxyl, superoxide, alkoxyl radicals and singlet
oxygen) were measured by electron paramagnetic resonance spin trapping method.
Fluorescence fingerprints of the same samples were obtained. Partial least
squares regression analysis was carried out to develop prediction models for ROS
scavenging capacity. The models were assessed by external validation.
Fluorescence fingerprint was found to accurately estimate the scavenging capacity
for the alkoxyl and superoxide radicals with the prediction error of
0.06mmoltroloxeq./mL and 0.31mmolalpha-lipoicacideq./mL with a coefficient of
determination of prediction (R2P) of 0.78 and 0.91, respectively.
PMID- 28490108
TI - Evaluation of 2-acetyl-1-pyrroline in foods, with an emphasis on rice flavour.
AB - The popcorn-like aroma compound 2-acetyl-1-pyrroline (2-AP) is a key contributor
to the desirable aroma of fragrant rice and is also important in the aroma of
other foods, such as pandan leaf, popcorn and Mediterranean sausage. It can be
formed enzymatically in the rice grain as it grows and is also formed, as part of
the Maillard reaction, when rice is heated. This review examines the formation of
2-AP in rice and other foods, particularly its formation during cooking, focusing
on the importance of the Maillard reaction between reducing sugar breakdown
products and 1-pyrroline derived from the amino acids proline and ornithine. The
synthesis of 2-AP is discussed alongside the attempts that have been made to
stabilise this relatively unstable compound. The analysis of 2-AP by instrumental
techniques, particularly gas chromatography-mass spectrometry and gas
chromatography-olfactometry, alongside the use of sensory studies, is also
discussed.
PMID- 28490109
TI - Effect of complexes of cyanidin-3-diglucoside-5-glucoside with rutin and metal
ions on their antioxidant activities.
AB - Studies have enabled a molecular understanding of the anthocyanin copigmentation
phenomenon over several decades. However, the effect of combinations of, or even
supramolecular assemblies of, anthocyanins with other phenols and/or metal ions
on their antioxidative activity was unclear. In this study, anthocyanin complexes
of cyanidin-3-diglucoside-5-glucoside (CY3D5G), rutin and Mg(II)/Fe(III) were
constructed, analyzed, and evaluated for their antioxidant effects. The CY3D5G
rutin-Fe(III) exhibited supramolecular properties via visible, CD and FTIR
spectra among complexes. The interaction of CY3D5G-rutin, CY3D5G-rutin-Mg(II), or
CY3D5G-rutin-Fe(III) was synergistic (P<0.05) in the ORAC assay. On cellular ROS
levels, the median effective concentration of the CY3D5G-rutin-Mg(II) was
7.76MUmol QE/L and exhibited a synergistic interaction (CI=0.67, P<0.05), whereas
the CY3D5G-rutin-Fe(III) (CI=0.79, P=0.074) was additive. The results indicate
that the antioxidant properties were affected by the molecular combination.
Additionally, Fe(III) might exhibit a negative effect, since the CY3D5G-Fe(III)
required a greater concentration than CY3D5G to achieve the same effect on cells.
PMID- 28490110
TI - Multivariate statistical analysis of the polyphenolic constituents in kiwifruit
juices to trace fruit varieties and geographical origins.
AB - Fifty-one kiwifruit juice samples of seven kiwifruit varieties from five regions
in China were analyzed to determine their polyphenols contents and to trace fruit
varieties and geographical origins by multivariate statistical analysis. Twenty
one polyphenols belonging to four compound classes were determined by ultra-high
performance liquid chromatography coupled with ultra-high-resolution TOF mass
spectrometry. (-)-Epicatechin, (+)-catechin, procyanidin B1 and caffeic acid
derivatives were the predominant phenolic compounds in the juices. Principal
component analysis (PCA) allowed a clear separation of the juices according to
kiwifruit varieties. Stepwise linear discriminant analysis (SLDA) yielded
satisfactory categorization of samples, provided 100% success rate according to
kiwifruit varieties and 92.2% success rate according to geographical origins. The
result showed that polyphenolic profiles of kiwifruit juices contain enough
information to trace fruit varieties and geographical origins.
PMID- 28490111
TI - Effect of high hydrostatic pressure and retrogradation treatments on structural
and physicochemical properties of waxy wheat starch.
AB - In this study, the effects of high hydrostatic pressure and retrogradation (HHPR)
treatments on in vitro digestibility, structural and physicochemical properties
of waxy wheat starch were investigated. The waxy wheat starch slurries (10%, w/v)
were treated with high hydrostatic pressures of 300, 400, 500, 600MPa at 20
degrees C for 30min, respectively, and then retrograded at 4 degrees C for 4d.
The results indicated that the content of slowly digestible starch (SDS) in HHPR
treated starch samples increased with increasing pressure level, and it reached
the maximum (31.12%) at 600MPa. HHPR treatment decreased the gelatinization
temperatures, the gelatinization enthalpy, the relative crystallinity and the
peak viscosity of the starch samples. Moreover, HHPR treatment destroyed the
surface and interior structures of starch granules. These results suggest that
the in vitro digestibility, physicochemical, and structural properties of waxy
wheat starch are effectively modified by HHPR.
PMID- 28490112
TI - Real-time monitoring of sucrose, sorbitol, d-glucose and d-fructose concentration
by electromagnetic sensing.
AB - Magnetic sensing at microwave frequencies for real-time monitoring of sucrose,
sorbitol, d-glucose and d-fructose concentrations is reported. The sensing
element was designed based on a coplanar waveguide (CPW) loaded with a split ring
resonator (SRR), which was fabricated on a DiClad 880 substrate with a thickness
of 1.6mm and relative permittivity (epsilonr) of 2.2. The magnetic sensor was
connected to a Vector Network Analyzer (VNA) and the electromagnetic interaction
between the samples and sensor was analyzed. The magnitude of the transmission
coefficient (S21) was used as an indicator to detect the solution sample
concentrations ranging from 0.04 to 0.20g/ml. The experimental results confirmed
that the developed system using microwaves for the real-time monitoring of
sucrose, sorbitol, d-glucose and d-fructose concentrations gave unique results
for each solution type and concentration. Moreover, the proposed sensor has a
wide dynamic range, high linearity, fast operation and low-cost.
PMID- 28490113
TI - Mitigating the in vitro enzymatic digestibility of noodles by aqueous extracts of
Malay cherry leaves.
AB - Aqueous extracts of Malay cherry leaves was incorporated into wheat, rice,
tapioca, and potato flours with the purpose to formulate noodles with slow
digestibility. In vitro digestion studies of these noodle prototypes were carried
out to evaluate their digestibility under simulated gastrointestinal conditions.
Upon incorporation of 2-8% of aqueous extracts, all four different types of
noodles exhibited dose dependency with varying degree of digestibility. The
greatest reduction in digestibility was observed in 8% tapioca noodles (69.2%)
after 180min. While there was no significant change on the physicochemical
properties of the noodles incorporated with different levels of aqueous extracts,
the color of noodles was darker. Overall, the results showed that incorporating
aqueous extracts is a promising way to mitigate the digestibility of starch in
different starchy foods. This study showed a viable way to produce starchy foods
with low glycemic index (GI) suitable for people with postprandial hyperglycemia.
PMID- 28490114
TI - Volatile organic compounds as markers of quality changes during the storage of
wild rocket.
AB - The quality of leafy green vegetables changes during storage. Leaves become
yellow or disintegrate, and an off-odor may develop. In addition, small amounts
of volatile organic compounds (VOCs) are released. In this study, the release of
acetone, carbon disulfide, dimethyl sulfide, nitromethane, pentane, 3
methylfuran, 2-ethylfuran, and dimethyl disulfide from wild rocket with different
initial qualities was monitored during 8d storage at 10 degrees C and correlated
to aerobic bacteria counts, yeast and mold counts, and degree of tissue
disintegration. The release of VOCs, except for 3-methylfuran, was influenced by
the initial quality of the leaves. The release of pentane and 2-ethylfuran was
related to the degree of tissue disintegration, and the release of dimethyl
sulfide and dimethyl disulfide was related to the total aerobic bacteria count.
The results demonstrated that VOCs can be used as markers for monitoring the
complex quality changes taking place in packaged fresh produce during storage.
PMID- 28490115
TI - Mechanistic insights into tyrosinase-mediated crosslinking of soy glycinin
derived peptides.
AB - Tyrosinase from Bacillus megaterium (TyrBm) was previously used to modulate soy
glycinin-based emulsions and gels. To study the crosslinking mechanism, TyrBm
oxidation of three tyrosine-containing octapeptides derived from glycinin was
analyzed by oxygen consumption measurements, absorbance and mass spectrometry. A
significant lag period and lower activity were measured when tyrosine was located
in the middle of the peptide chain. Mass spectrometry analysis showed that these
peptides are crosslinked via the oxidative quinone ring of the tyrosine residue
by aryl-alkylamine addition or aryloxy radical coupling to form di-DOPA (3,4
dihydroxyphenylalanine). In contrast, peptides containing tyrosine in the N- or C
terminus, were rapidly oxidized forming multimer units within thirty minutes.
When small amino acids were adjacent to the terminus tyrosine, formation of di
tyrosine was observed. This work confirms that protein crosslinking by TyrBm
occurs by several chemical mechanisms and may assist in designing peptide-based
inhibitors for the food and cosmetic applications.
PMID- 28490116
TI - The effect of Maillard reaction products and yeast strain on the synthesis of key
higher alcohols and esters in beer fermentations.
AB - The effect of Maillard reaction products (MRPs), formed during the production of
dark malts, on the synthesis of higher alcohols and esters in beer fermentations
was investigated by headspace solid-phase microextraction GC-MS. Higher alcohol
levels were significantly (p<0.05) higher in dark malt fermentations, while the
synthesis of esters was inhibited, due to possible suppression of enzyme activity
and/or gene expression linked to ester synthesis. Yeast strain also affected
flavour synthesis with Saccharomyces cerevisiae strain A01 producing considerably
lower levels of higher alcohols and esters than S288c and L04. S288c produced
approximately double the higher alcohol levels and around twenty times more
esters compared to L04. Further investigations into malt type-yeast strain
interactions in relation to flavour development are required to gain better
understanding of flavour synthesis that could assist in the development of new
products and reduce R&D costs for the industry.
PMID- 28490117
TI - Carotenoid retention in biofortified maize using different post-harvest storage
and packaging methods.
AB - Orange maize is being promoted as a source of provitamin A carotenoids (pVAC) in
Zambia. Carotenoid retention in orange maize grains stored in metal silos,
multilayer polyethylene and common woven bags, and maize meal packaged in single
and multilayer polyethylene bags was evaluated. Significant differences in total
pVAC retention were found between grain storage methods (48.1-57.2%) after
6months of storage. Total pVAC retention in hammer meal (73.1-73.5%) was higher
than in breakfast meal (64.3-69.3%) after 4months of storage; however, no
differences in pVAC retention were found between meal types when stored in single
and multilayer polyethylene bags. In general, beta-cryptoxanthin (betaCX) had
higher retention than beta-carotene (betaC). Potential contribution of stored
orange maize to the estimated average requirement of children and women was 26.5%
and 24.3%, respectively. Orange maize meal can provide significant amounts of
provitamin A to diets of Zambians even after 4months of storage.
PMID- 28490118
TI - Study of phenolic extractability in grape seeds by means of ATR-FTIR and Raman
spectroscopy.
AB - Near infrared hyperspectral imaging has been applied to grape seeds in order to
select a representative subset of samples according to their spectral features in
the 900-1700nm range. Afterwards, selected grape seeds have been classified
according to their total phenol and flavanol extractabilities. In this way,
samples were sorted in three different groups identified as low, medium and high
extractability levels. In order to establish the chemical structures which can be
responsible for the different extractabilities, vibrational spectroscopy has been
applied to the non-extracted material after seed extractions. Attenuated total
reflectance Fourier transform infrared (ATR-FTIR) and Raman spectra of non
extracted seed material have been recorded and their main spectral features have
been linked to extractabilities of flavanolic and total phenolic compounds. The
vibrational spectroscopic analysis confirms that grape seed phenolic
extractability is influenced by the cell wall composition (polysaccharides,
lignins, pectins) and by the degree of esterification of pectins.
PMID- 28490119
TI - Complex interactive effects of ripening degree, malaxation duration and
temperature on Oblica cv. virgin olive oil phenols, volatiles and sensory
quality.
AB - The interactive effects of ripening degree, malaxation duration and temperature
on Oblica cv. (Olea europaea L.) virgin olive oil phenols, volatiles, and sensory
quality were investigated. Olives were picked at three ripening degrees with
International Olive Council indices of 0.68, 2.48 and 4.10, and processed by
malaxation at 22 and 30 degrees C, and at both temperatures for 30 and 60min.
Ripening exhibited the strongest effect, and malaxation duration the weakest.
Phenols were generally found to decrease during ripening; however 3,4-DHPEA-EDA
and p-HPEA-EDA increased. Similar behaviour was observed for (E)-2-hexenal.
Higher malaxation temperature induced an increase in particular important phenols
and C6 alcohols, while C6 aldehydes mostly decreased. Interactions between the
factors were established, mostly between ripening degree and malaxation
temperature: the effect of the latter was most pronounced for ripe olives,
especially for 3,4-DHPEA-EDA, p-HPEA-EDA and C6 volatiles. Sensory attributes
were generally in agreement with the chemical composition.
PMID- 28490120
TI - Evaluation of antioxidant potential of Artocarpus heterophyllus L. J33 variety
fruit waste from different extraction methods and identification of phenolic
constituents by LCMS.
AB - Artocarpus heterophyllus J33 (AhJ33) fruit is a popular and valuable jackfruit
variety in Malaysia. For export, the pulp has to be separated from the skin which
is usually discarded. Hence, the conversion of the fruit waste to food products
with economic value needs to be explored utilizing the waste to wealth concept.
This paper reports the evaluation of antioxidant potential of AhJ33 fruit waste
(rind and rachis) extracts from three different extraction methods (maceration,
percolation and Soxhlet). The antioxidant potential was assessed by DPPH radical
scavenging, FRAP and beta-carotene bleaching assays. The total phenolic and total
flavonoid contents were estimated by TPC and the TFC assays. For both rind and
rachis, the maceration technique yielded extracts with the strongest antioxidant
activities which correlated with the highest TPC and TFC values. TOF LCMS
analyses identified two phenolic acids as the major constituents responsible for
the antioxidant activity of the active extracts.
PMID- 28490121
TI - Isotope dilution HPLC-MS/MS for simultaneous quantification of acrylamide and 5
hydroxymethylfurfural (HMF) in thermally processed seafood.
AB - The objective of this study was to develop an accurate, robust and rapid HPLC
MS/MS-based method capable of quantifying acrylamide and 5-hydroxymethylfurfural
(HMF) simultaneously. A Phenomenex Synergi Fusion-RP C18 column (50mm*2.5mm,
2MUm) was used, and the MS/MS instrument was operated in multiple reaction
monitoring mode. The isotope dilution method was used to correct for the matrix
effect from samples. This method demonstrated low limits of quantification
(2.12ng/mL for acrylamide and 4.86ng/mL for HMF) and excellent linearity
(R2>0.999). This method also demonstrated excellent quantification accuracy,
precision, and recovery (87-110%). Using the method developed, target analytes
were quantified in 14 thermally-processed seafood samples. Resulting
concentrations ranged from 5.58 to 50.35MUg/kg for acrylamide, and from 12.54 to
2276.44MUg/kg for HMF. The proposed isotope dilution HPLC-MS/MS method is a valid
and rapid technique for simultaneous analysis of acrylamide and HMF in seafood.
PMID- 28490122
TI - Anthocyanin condensed forms do not affect color or chemical stability of purple
corn pericarp extracts stored under different pHs.
AB - Purple corn is rich in anthocyanins, some of which are condensed with flavanols.
The aim was to determine the impact of anthocyanin condensed forms extracted from
purple corn pericarp on color and chemical stability at different pHs compared
with the complete extract, and an extract without condensed forms. Extracts were
dissolved at pH values ranging from 2.0 to 6.0 and stored for 12weeks at 22
degrees C. Color stability of anthocyanins decreased as the pH increased. Slight
color differences were observed throughout time at pH 2 (DeltaE from 0.2 to 3.6).
After 12weeks, pH 6 caused substantial changes in color (DeltaE=17.7 to 47.5);
and reduced the predicted half-life of total anthocyanins (ranging from 1.8 to
3weeks), compared to pH 2 (44.6 to 60.7weeks). Condensed forms had degradation
kinetics similar to monomeric anthocyanins. Purple corn pericarp pigments can be
used in acid beverages with an acceptable shelf-life.
PMID- 28490123
TI - Kinetics of conversion of dihydroxyacetone to methylglyoxal in New Zealand manuka
honey: Part IV - Formation of HMF.
AB - During a study of the conversion of dihydroxyacetone (DHA) to methylglyoxal (MGO)
in maturing New Zealand manuka honey, the kinetics of formation of 5
(hydroxymethyl)furfural (HMF) was studied at temperatures from 4 to 37 degrees C.
Formation of HMF was first-order during an induction period and zero-order
thereafter indicating that the mechanism includes the formation of certain
critical intermediates and that these require time to build up; the duration of
the induction period depended primarily upon temperature. The zero-order rate
constant at 37 degrees C was the same for manuka honey and clover honey doped
with 2000 or 10,000mg/kg DHA and for artificial honey with 2000mg/kg of DHA and
either alanine or proline and alanine added. Zero-order rate constants for
artificial honey with added amino acids were less than for a control without
amino acids. A simulation was created to predict the formation of HMF over time
at 37 degrees C in manuka honey.
PMID- 28490124
TI - Explaining the antioxidant activity of some common non-phenolic components of
essential oils.
AB - Limonene, linalool and citral are common non-phenolic terpenoid components of
essential oils, with attributed controversial antioxidant properties. The
kinetics of their antioxidant activity was investigated using the inhibited
autoxidation of a standard model substrate. Results indicate that antioxidant
behavior of limonene, linalool and citral occurs by co-oxidation with the
substrate, due to very fast self-termination and cross-termination of the
oxidative chain. Rate constants kp and 2kt, (M-1s-1) at 30 degrees C were 4.5 and
3.5*106 for limonene, 2.2 and 9.0*105 for linalool and 39 and 1.0*108 for citral.
Behavior is bimodal antioxidant/pro-oxidant depending on the concentration.
Calculations at the M05/6-311+g(2df,2p) level indicate that citral reacts
selectively at the aldehyde C-H having activation enthalpy and energy
respectively lower by 1.3 and 1.8kcal/mol compared to the most activated allyl
position. Their termination-enhancing antioxidant chemistry might be relevant in
food preservation and could be exploited under appropriate settings.
PMID- 28490125
TI - Colour and in vitro quality attributes of walnuts from different growing
conditions correlate with key precursors of primary and secondary metabolism.
AB - Walnuts (Juglans regia L.) are well known for their flavour, nutritional and
health properties. The light colour of walnuts is a quality attribute that leads
to consumer preference. The aim of this study was to correlate attributes such as
colour and antioxidant capacity with the precursors of primary and secondary
metabolism. Two growing areas and four different colours of walnuts cv. Chandler
from the central region of Chile were evaluated. Walnuts grown in the zone with
Andes Mountains influence showed higher (p<0.05) sugar and unsaturated fatty acid
contents, which could be attributed to lower minimum temperatures during seed
filling. Extra light walnuts had higher (p<0.05) total phenolic compounds,
antioxidant capacity and arbutin levels than amber walnuts. To the best of our
knowledge, this is the first time that arbutin has been reported in walnuts and
could provide the first insight into how enzymatic browning is prevented in the
Chandler cultivar.
PMID- 28490126
TI - Phytochemical profiles and antioxidant activity of processed brown rice products.
AB - The phytochemical profiles and antioxidant activity of free, soluble-conjugated,
and bound fractions of brown rice and its processed products (textured rice,
cooked rice and rice noodle) were studied. Nineteen phenolic acids were
identified. Trans-ferulic acid was the most abundant monomeric phenolic acid with
trans-trans-8-O-4' diferulic acid being most abundant diferulic acid. Processing
increased the content of free phenolic acids, but decreased the content of
soluble-conjugated phenolic acids. The content of bound phenolic acids was
increased by improved extrusion cooking technology and cooking, but not affected
by rice noodle extrusion. The total phenolic contents and antioxidant activities
of free and soluble-conjugated fractions were decreased after processing, whereas
those of bound fraction were increased by improved extrusion cooking technology
and cooking, but not affected by rice noodle extrusion. Results indicated that
whole foods designed for reducing chronic disease risk need to consider the
effects of processing on phytochemical profiles and antioxidant activity of whole
grains.
PMID- 28490127
TI - Milk bioactive peptide database: A comprehensive database of milk protein-derived
bioactive peptides and novel visualization.
AB - During processing and digestion, milk proteins are disassembled into peptides
with an array of biological functions, including antimicrobial, angiotensin
converting enzyme inhibition, antioxidant, opioid, and immunomodulation. These
functions are summarized in numerous reviews, yet information on which peptides
have which functions remains scattered across hundreds of research articles. We
systematically searched the literature for all instances of bioactive peptides
derived from milk proteins from any mammalian source. The data were compiled into
a comprehensive database, which can be used to search for specific functions,
peptides, or proteins (http://mbpdb.nws.oregonstate.edu). To review this large
dataset, the bioactive peptides reported in the literature were visually mapped
on the parent protein sequences, providing information on sites with highest
abundance of bioactive peptides.
PMID- 28490129
TI - Tyrosinase inhibitory mechanism of betulinic acid from Dillenia indica.
AB - The fruit of Dillenia indica L. is extensively used as a food additive. Betulinic
acid (BA) is the most prominent secondary metabolite present in D. indica. This
study screened the bioassay guided isolation of BA from D. indica and explored
its tyrosinase inhibitory mechanism. Half maximal inhibitory concentration (IC50)
of BA were calculated as 13.93uM and 25.66uM for diphenolase and monophenolase.
Enzyme kinetic analysis revealed that BA inhibited tyrosinase activity non
competitively. Further, conformational analysis of tyrosinase with BA was
measured by fluorescence and circular dichroism spectroscopy. These results
implied that diminish rigidity of enzyme might disturb the catalytic conformation
of tyrosinase. Moreover, In-silico analysis confirmed probable binding polar and
non-polar region on the active site of tyrosinase. Based on these findings, we
suggest that BA from D. indica may be useful in preventing enzymatic browning
reactions in food products.
PMID- 28490128
TI - Nepsilon-(carboxymethyl)lysine and Nepsilon-(carboxyethyl)lysine in tea and the
factors affecting their formation.
AB - The levels of Nepsilon-(carboxymethyl)lysine (CML) and Nepsilon
(carboxyethyl)lysine (CEL) in 99 tea samples from 14 geographic regions,
including 44 green, 7 oolong, 41 black, and 7 dark teas were determined by liquid
chromatography-tandem mass spectrometry (LC-MS/MS). The CML and CEL contents
varied from 11.0 to 1701MUg/g tea and 4.6 to 133MUg/g tea, respectively. Dark tea
presented the highest levels of CML and CEL, whereas green and oolong teas
presented the lowest levels. Five kinds of catechins in the tea were also
analyzed, and spearman's correlation coefficients showed that all the catechins
negatively correlated with CML and CEL. The results suggested that withering,
fermentation and pile fermentation may facilitate the formation of CML and CEL.
Catechins might inhibit the formation of CML and CEL, but their inhibitory
effects may be affected by tea processing. The results of this study are useful
for the production of healthier tea.
PMID- 28490130
TI - Formation of lactoferrin/sodium caseinate complexes and their adsorption
behaviour at the air/water interface.
AB - This research investigated the complexation behaviour between lactoferrin (Lf)
and sodium caseinate (NaCas) before and after heat treatment. The results showed
that heating facilitated their interaction and different complexes were formed at
different Lf/NaCas ratios. The presence of low concentrations of NaCas resulted
in the rapid precipitation of Lf, while no precipitation was observed at the
NaCas concentrations higher than Lf/NaCas ratio of 2:1. The formed complexes at
the ratio of 2:1 have an average diameter of 194+/-9.0nm and they exhibited a
great capacity in lowering the air/water interfacial tension. Further increase of
NaCas concentration to ratios of 1:1 and 1:2 resulted in the formation of smaller
complexes with average diameters of 60+/-2.5nm. The complexes formed at these two
ratios showed similar adsorption behaviour at the air/water interface and they
exhibited lower capacity in decreasing the interfacial tension than the ratio of
2:1.
PMID- 28490131
TI - Influence of the chemical structure on the odor characters of beta-citronellol
and its oxygenated derivatives.
AB - beta-Citronellol, 1, and citronellyl acetate, 2, are renowned fragrant
constituents in perfumes and flavoring agents in foods and beverages. Both
substances smell citrussy, fresh and floral. To elucidate the structural features
required for these sensory effects, six C-8 oxygenated derivatives of 1 and 2
were synthesized and analytically characterized. All compounds were tested for
their odor qualities and odor thresholds in air, revealing that there were no
significant differences in odor impressions from the parent monoterpenes and
their derivatives in most cases; however, substantial differences in their odor
threshold values were observed, with beta-citronellol as the most potent
(10ng/Lair) and 8-hydroxycitronellyl acetate as the least potent odorant
(1261ng/Lair). 8-Oxocitronellyl acetate was the only compound that was described
with divergent odor attributes, namely musty, rotten and coconut-like. 8
Carboxycitronellol and 8-carboxycitronellyl acetate were found to be odorless.
PMID- 28490132
TI - Heat-induced inactivation mechanism of soybean Bowman-Birk inhibitors.
AB - Due to the complications of the soymilk system, the heat-induced Bowman-Birk
inhibitor (BBI) inactivation mechanism is not well known. In this study, two BBI
samples with low and high purities were prepared from soymilk. It was confirmed
that three groups (A, C, and D) of BBI, which are contained in soybean seeds,
were transferred into soymilk during processing. On heating, it was found that 1)
the two subdomains of BBI were not equally heat stable, 2) the conformation of
BBI gradually changed, 3) some amino acid residues (namely, cystine, serine and
lysine) in BBI were degraded, 4) BBI did not tend to form intermolecular cross
links with another BBI, but did slightly with non-BBI proteins. Based on some
previous studies, the conformational change of BBI was attributed to beta
elimination reactions on the amino acid residues of BBI and the subsequent
intramolecular reactions induced by the products yielded by the beta-elimination
reactions.
PMID- 28490133
TI - Nano-ZnO/carboxymethyl cellulose-based active coating impact on ready-to-use
pomegranate during cold storage.
AB - Minimally processed pomegranate rapidly loses its overall quality because of high
water loss and microbial contamination. Nano-ZnO in combination with
carboxymethyl cellulose (CMC) coating was used on pomegranate arils. Arils were
dipped for 4min in distilled water (control), 0.1 or 0.2% (w/v) nano-ZnO
suspension and then ZnO treated arils were coated with 0.5% (w/v) CMC and stored
for 12days at 4 degrees C. Coatings decreased total yeast+mold during 12days of
storage while total mesophilic bacteria was decreased during 6days of storage.
Coatings decreased weight loss and also the greatest juice percent was in coated
arils. Soluble solids content decreased during storage with no significant
difference between treatments. CMC+0.2% nano-ZnO suppressed total phenol changes.
Total anthocyanin, vitamin C, and antioxidant capacity were higher in coated
arils. These findings suggest that nano-ZnO+CMC coating has the potential to
extend minimally processed pomegranate storage life.
PMID- 28490134
TI - Changes in the structure and dissociation of soybean protein isolate induced by
ultrasound-assisted acid pretreatment.
AB - Structure and dissociation properties of soybean protein isolate (SPI) induced by
ultrasound and acid were investigated. Results of solubility showed that
ultrasound-assisted acid had no effect on the content of soluble aggregates in
SPI. Increase of fluorescence intensity and red-shift of maximum emission
wavelength indicated that acid induced molecular unfolding of SPI and exposure of
hydrophobic groups. Circular dichroism spectra showed that ultrasound-assisted
acid pretreatment resulted in increases in the alpha-helix content by 29.2% and
random coils content by 8.3%, while beta-sheet decreased by 13.4% (P<0.05), as
compared with those of control. Analysis of sodium dodecyl sulfate-polyacrylamide
gel electrophoresis and atomic force microscope revealed that the contents of
small subunits and particle increased significantly when SPI treated by
ultrasound-assisted acid comparing with the SPI treated by single acid and
ultrasound treatment. This study illustrated the ultrasound and acid have
synergistic effect on the structure unfolding and dissociation of SPI.
PMID- 28490135
TI - Polyunsaturated lipids and vitamin A oxidation during cod liver oil in vitro
gastrointestinal digestion. Antioxidant effect of added BHT.
AB - The extent of cod liver oil hydrolysis and oxidation during in vitro
gastrointestinal digestion was investigated by Proton Nuclear Magnetic Resonance
(1H NMR) and Solid Phase Microextraction-Gas Chromatography/Mass Spectrometry
(SPME-GC/MS). These techniques evidenced the degradation of polyunsaturated omega
3 and omega-6 lipids and, for the first time, that of vitamin A, naturally
present in cod liver oil. Cis,trans-conjugated dienes associated with
hydroperoxides, as well as monoepoxides, cis,trans-2,4-alkadienals, 4-hydroperoxy
and 4-hydroxy-2-alkenals, and several vitamin A derived metabolites were
generated. Moreover, the effect of the addition of the synthetic antioxidant 2,6
di-tert-butyl-hydroxytoluene (BHT) at 20 and 800ppm was tackled. Both techniques
showed BHT to be efficient in limiting oxidation reactions during digestion,
almost inhibiting them at 800ppm. Therefore, the simultaneous intake of
antioxidants with cod liver oil should be considered, in order to increase
polyunsaturated lipid and vitamin A bioaccessibility and avoid formation of toxic
oxidation compounds like oxygenated alpha,beta-unsaturated aldehydes.
PMID- 28490136
TI - Antioxidative capacity and binding affinity of the complex of green tea catechin
and beta-lactoglobulin glycated by the Maillard reaction.
AB - Major green tea catechin, epigallocatechin-3-gallate (EGCG), binds non-covalently
to numerous dietary proteins, including beta-lactoglobulin of cow's milk. The
effects of glycation of proteins via Maillard reaction on the binding capacity
for polyphenols and the antiradical properties of the formed complexes have not
been studied previously. Binding constant of BLG glycated by milk sugar lactose
to EGCG was measured by the method of fluorophore quenching. Binding of EGCG was
confirmed by CD and FTIR. The antioxidative properties of the complexes were
examined by measuring ABTS radical scavenging capacity, superoxide anion
scavenging capacity and total reducing power assay. Glycation of BLG does not
significantly influence the binding constant of EGCG for the protein.
Conformational changes were observed for both native and glycated BLG upon
complexation with EGCG. Masking effect of polyphenol complexation on the
antioxidative potential of the protein was of the similar degree for both
glycated BLG and native BLG.
PMID- 28490137
TI - Fractionation and identification of novel antioxidant peptides from buffalo and
bovine casein hydrolysates.
AB - Buffalo and bovine caseins were hydrolysed by alcalase and trypsin to produce
novel antioxidant peptides. The casein hydrolysates were purified using
ultrafiltration (UF) and further characterized by RP-HPLC. The fractions produced
higher antioxidant activities were identified for their peptides using LC MS/MS.
All UF-VI (MW<1kDa) fractions showed higher antioxidant activity. Hydrolysate
produced by alcalase for buffalo casein (UF-VI with 54.84-fold purification)
showed higher antioxidant activity than that obtained by trypsin. Trypsin
hydrolysate contained high amount of hydrophobic amino acids while alcalase
hydrolysate consisted mainly of Ser, Arg, Ala and Leu. The antioxidant peptides
identified by LC MS/MS were RELEE, MEDNKQ and TVA, EQL in buffalo casein
hydrolysates produced by trypsin and alcalase, respectively. Mechanism and
reaction pathways of selected antioxidant peptides with ABTS were proposed.
Conclusively, buffalo casein provided antioxidant peptides similar to bovine,
suggesting that buffalo casein is a novel source of antioxidant.
PMID- 28490138
TI - Contamination of Chinese salted fish with volatile N-nitrosamines as determined
by QuEChERS and gas chromatography-tandem mass spectrometry.
AB - The QuEChERS sample preparation method and gas chromatography-tandem mass
spectrometry were employed to determine nine volatile N-nitrosamines (VNAs) in
Chinese salted fish. This method was validated by considering calibration plot
linearity, selectivity, matrix effects, trueness, precision, limits of
quantification and specificity. Fifty-four samples of Chinese salted fish
obtained from five provinces were analyzed. The results indicated that the
concentrations of one VNA, N-nitrosodimethylamine in 57.4% of the samples
exceeded the acceptable limit (the China national standard value of 4MUgkg-1),
and total VNA contents in 68.5% of the samples exceeded the acceptable United
States Department of Agriculture limit of 10MUgkg-1 for cured meats. In addition,
total VNAs in marine salted fish that exceeded the acceptable limit were
statistically higher than those in freshwater salted fish. The present study
suggests that VNA contamination in Chinese salted fish continues to be serious,
and deserves stricter management by the authorities.
PMID- 28490139
TI - Development of a competitive immunochromatographic assay for the sensitive
detection of amantadine in chicken muscle.
AB - Amantadine (AMD) is a prohibitive veterinary medicine in the entire world. In
this study, a sensitive colloidal gold immunochromatographic assay (CGICA) was
established for the rapid semi-quantitative detection of AMD in chicken muscle.
Under optimal conditions, the detection results were obtained in 12min with a
limit of detection for 1.80ng/mL. CGICA presented a good linear range from
2.5ng/mL to 25ng/mL, with only 11.5% cross-reactivity with rimantadine. The
recovery rates for the fortified samples were ranged from 81% to 120%. The
coefficient of variation of the intra-assay and inter-assay was less than 15%.
The accuracy of CGICA was confirmed by systematically comparing the result of the
proposed method with enzyme-linked immunosorbent assay and ultra-high-performance
liquid chromatography-tandem mass spectrometry. Given the advantages of its
simplicity, convenience, and speediness, the proposed CGICA is suitable for the
on-site rapid detection of AMD in chicken muscle.
PMID- 28490140
TI - Evaluation of antioxidant capacity and flavor profile change of pomegranate wine
during fermentation and aging process.
AB - Antioxidant properties and flavor characteristic profile of pomegranate wine
during winemaking were investigated. The total phenol content and radical
scavenging activity exhibited a slightly decrease in the end edge. Punicalagins
and gallic acid were revealed to be the most abundant phenolic compounds,
followed by ellagic acid and vanillic acid. These constituents were mainly
responsible for the effective antioxidant capacity of pomegranate wine. The major
changes of flavor qualities occurred in the initial stage, particularly 0-4day of
fermentation. Fermentation significantly reduced the relative content of
aldehydes, ketones, heterocyclic and aromatic compounds, but promoted the
generation of esters and alcohols. This is the first time of using E-nose and E
tongue to monitor odour and taste changes in the brewing process of pomegranate
wine. The study may provide a promising instruction for improving functional
features and quality control of the pomegranate wine.
PMID- 28490141
TI - Carotenoid profiling of red navel orange "Cara Cara" harvested from five regions
in China.
AB - Understanding the composition and content of carotenoids in red-flesh navel
orange "Cara Cara" cultivated in different regions is valuable for its nutrition
assessment and fruit processing control. Herein, the carotenoids of "Cara Cara"
fruits, harvested from five typical citrus growing regions of China, were
identified and quantified by HPLC-DAD coupled with HPLC-DAD-APCI-MS/MS. In
saponified extracts, 19 free carotenoids including 8 carotenes and 11
xanthophylls were identified. In unsaponified extracts, 83.83-93.83% xanthophylls
were esterified and 19 esters were inferred, with the 9-cis-violaxanthin ester
confirmed as the dominant component. The carotenoid contents showed difference
among the "Cara Cara" fruits from different growing regions, which might be
attributed to the local environmental conditions, and the temperature was found
directly correlated with total carotenoids content of "Cara Cara". The data
obtained in this study will facilitate the nutritional evaluation of "Cara Cara"
and provide beneficial guidance for fruit processing.
PMID- 28490142
TI - Relation between polyphenol profile and antioxidant capacity of different
Argentinean wheat varieties. A Boosted Regression Trees study.
AB - We report the polyphenol profile and antioxidant capacity (AC) of 12 Argentinean
wheat varieties from different regions. The polyphenol profile was studied by
HPLC-MS. The AC was measured by TEAC and FRAP. Twenty-five polyphenols were
identified. ACA 315 and KLEIN GUERRERO varieties showed the highest content of
polyphenols, whereas BIOINTA 3004, KLEIN CAPRICORNIO and LE 2330 showed the
lowest one. ACA 315 presented the highest AC, while BIOINTA 3004 and KLEIN
CAPRICORNIO showed the lowest one. Boosted Regression Trees (BRT) analyses helped
finding significant correlations between AC and polyphenol profile, being
hydroxybenzoic acid diglucoside, tryptophan, chrysoeriol-6,8-di-C-pentoside and
isomers 4, 5, 9 and 12 of diferulic acids key compounds to explain the observed
AC. To our knowledge, this is the first report on the interaction between the
environment and wheat genotypes evaluated by BRT, showing how the whole
polyphenol profile can explain the AC in wheat.
PMID- 28490143
TI - Method for sampling and analysis of volatile biomarkers in process gas from
aerobic digestion of poultry carcasses using time-weighted average SPME and GC
MS.
AB - A passive sampling method, using retracted solid-phase microextraction (SPME) -
gas chromatography-mass spectrometry and time-weighted averaging, was developed
and validated for tracking marker volatile organic compounds (VOCs) emitted
during aerobic digestion of biohazardous animal tissue. The retracted SPME
configuration protects the fragile fiber from buffeting by the process gas
stream, and it requires less equipment and is potentially more biosecure than
conventional active sampling methods. VOC concentrations predicted via a model
based on Fick's first law of diffusion were within 6.6-12.3% of experimentally
controlled values after accounting for VOC adsorption to the SPME fiber housing.
Method detection limits for five marker VOCs ranged from 0.70 to 8.44ppbv and
were statistically equivalent (p>0.05) to those for active sorbent-tube-based
sampling. The sampling time of 30min and fiber retraction of 5mm were found to be
optimal for the tissue digestion process.
PMID- 28490144
TI - Influence of the chemical structure on the odor qualities and odor thresholds of
guaiacol-derived odorants, Part 1: Alkylated, alkenylated and methoxylated
derivatives.
AB - Guaiacol and its derivatives are commonly found in nature and are known for their
characteristic smoky, clove-like and vanilla-like smells. However, there is no
systematic investigation of the smell properties of structurally related guaiacol
derivatives. In order to establish a comprehensive database on this olfactorily
interesting substance class, odor thresholds in air and odor qualities of
guaiacol and its alkylated, alkenylated, and methoxylated derivatives were
determined by means of gas chromatography-olfactometry. All compounds elicited
characteristic smoky/smoked ham-like, vanilla-like/sweet and/or clove-like smell
impressions. The odor thresholds of the compounds were generally very low,
ranging from 0.00018 to 111ng/Lair. The lowest thresholds were determined for 5
methoxyguaiacol and guaiacol, followed by 4-ethyl- and 4-vinylguaiacol. Some
inter-individual differences in the threshold values between panelists were
observed, with highest variation in the individual values of cis-6-propenyl-,
trans-6-propenyl- and 3-vinylguaiacol. The smell impressions, on the other hand,
were quite consistent.
PMID- 28490145
TI - Thermal and high pressure inactivation kinetics of blueberry peroxidase.
AB - This study for the first time investigated the stability and inactivation
kinetics of blueberry peroxidase in model systems (McIlvaine buffer, pH=3.6, the
typical pH of blueberry juice) during thermal (40-80 degrees C) and combined high
pressure-thermal processing (0.1-690MPa, 30-90 degrees C). At 70-80 degrees C,
the thermal inactivation kinetics was best described by a biphasic model with
~61% labile and ~39% stable fractions at temperature between 70 and 75 degrees C.
High pressure inhibited the inactivation of the enzyme with no inactivation at
pressures as high as 690MPa and temperatures less than 50 degrees C. The
inactivation kinetics of the enzyme at 60-70 degrees C, and pressures higher than
500MPa was best described by a first order biphasic model with ~25% labile
fraction and 75% stable fraction. The activation energy values at atmospheric
pressure were 548.6kJ/mol and 324.5kJ/mol respectively for the stable and the
labile fractions.
PMID- 28490146
TI - Development and optimization of an efficient qPCR system for olive authentication
in edible oils.
AB - The applicability of qPCR in olive-oil authentication depends on the DNA obtained
from the oils and the amplification primers. Therefore, four olive-specific
amplification systems based on the trnL gene were designed (A-, B-, C- and D-trnL
systems). The qPCR conditions, primer concentration and annealing temperature,
were optimized. The systems were tested for efficiency and sensitivity to select
the most suitable for olive oil authentication. The selected system (D-trnL)
demonstrated specificity toward olive in contrast to other oleaginous species
(canola, soybean, sunflower, maize, peanut and coconut) and showed high
sensitivity in a broad linear dynamic range (LOD and LOQ: 500ng - 0.0625pg). This
qPCR system enabled detection, with high sensitivity and specificity, of olive
DNA isolated from oils processed in different ways, establishing it as an
efficient method for the authentication of olive oil regardless of its category.
PMID- 28490147
TI - Thermal degradation kinetics of anthocyanins extracted from jucara (Euterpe
edulis Martius) and "Italia" grapes (Vitis vinifera L.), and the effect of
heating on the antioxidant capacity.
AB - The effect of temperature on the degradation of anthocyanins in jucara and
"Italia" grape extracts was determined between 50 and 90 degrees C. For both
species, thermal degradation followed a first-order kinetic model. The decimal
reduction time decreased with increasing temperature, and dependence on the
thermodegradable factor was lower at higher temperatures. The anthocyanins from
jucara degraded more slowly than those extracted from "Italia" grapes. The
activation enthalpy and free energy of inactivation indicated an endothermic
reaction, not spontaneous degradation, whereas the activation entropy suggested
that the transition state has less structural freedom than that of the reactants.
The antioxidant capacity of the extracts was reduced when subjected to 90 degrees
C heat treatment, however, significant quantities of this bioactive compound
still remained.
PMID- 28490148
TI - Characterisation of aroma-active and off-odour compounds in German rainbow trout
(Oncorhynchus mykiss). Part II: Case of fish meat and skin from earthen-ponds
farming.
AB - Odorous molecules in earthen-ponds rainbow trout aquaculture farming in Germany
were investigated with a special focus on musty-earthy off-odorants. To this aim,
fish meat and skin were extracted using solvent-assisted flavour evaporation
(SAFE) and were mildly concentrated; extracts were subsequently analysed by means
of one- and two-dimensional high-resolution gas chromatography coupled with mass
spectrometry and olfactometry (GC-MS/O and 2D-HRGC-MS/O). Aroma extract dilution
analysis (AEDA) of the solvent extracts revealed the presence of 76 odorants of
which 75 were successfully identified. Thereby, rotundone (black pepper) is
described for the first time as an odour-active substance in fish. Moreover, a
series of compounds is described for the first time in German aquaculture rainbow
trout fish, including, amongst others, (E,Z,Z)-2,4,7-tridecatrienal, (E)-4,5
epoxy-(E)-2-decenal, 4-ethyloctanoic acid, 3-methylindole (skatole), d-limonene,
and indole. The analytical findings were further compared to sensory evaluation
of the samples, and previously obtained data on the respective aquacultural
water.
PMID- 28490149
TI - Aroma profile and sensory characteristics of a sulfur dioxide-free mulberry
(Morus nigra) wine subjected to non-thermal accelerating aging techniques.
AB - The present study was undertaken to assess accelerating aging effects of high
pressure, ultrasound and manosonication on the aromatic profile and sensorial
attributes of aged mulberry wines (AMW). A total of 166 volatile compounds were
found amongst the AMW. The outcomes of the investigation were presented by means
of geometric mean (GM), cluster analysis (CA), principal component analysis
(PCA), partial least squares regressions (PLSR) and principal component
regression (PCR). GM highlighted 24 organoleptic attributes responsible for the
sensorial profile of the AMW. Moreover, CA revealed that the volatile composition
of the non-thermal accelerated aged wines differs from that of the conventional
aged wines. Besides, PCA discriminated the AMW on the basis of their main
sensorial characteristics. Furthermore, PLSR identified 75 aroma compounds which
were mainly responsible for the olfactory notes of the AMW. Finally, the overall
quality of the AMW was noted to be better predicted by PLSR than PCR.
PMID- 28490150
TI - A simple and sensitive vortex-assisted ionic liquid-dispersive microextraction
and spectrophotometric determination of selenium in food samples.
AB - In the present study, a novel and eco-friendly vortex-assisted ionic liquid-based
microextraction method was developed for the determination of selenium in food.
The microextraction method is based on the liberation of iodine in the presence
of selenium; the liberated iodine reacts with I- to form I3-. Anionic I3- reacts
with cationic crystal violet dye, and the product is extracted into 1-hexyl-3
methylimidazolium hexafluorophosphate phase in the presence of Triton X-114. The
proposed method is linear in the range of 2.0-70ugL-1 and has a detection limit
of 9.8*10-2ugL-1. Relative standard deviations were 3.67% and 2.89% for the five
replicate measurements of 14 and 35ugL-1 Se(IV), respectively. The proposed
method was successfully applied to different food samples (NIST SRM 2976 mussel
tissue, pepper, ginger, wheat flour, red lentil, traditional soup, cornflour,
cornstarch, and garlic) after microwave digestion.
PMID- 28490151
TI - Preface: Invited Issue Editor, Professor Joong-Uhn Choi, and the Era of
Neuroendoscopy.
PMID- 28490152
TI - Keyhole Approach and Neuroendoscopy for Cerebral Aneurysms.
AB - Treating diseases in the field of neurosurgery has progressed concomitantly with
technical advances. Here, as a surgical armamentarium for the treatment of
cerebral aneurysms, the history and present status of the keyhole approach and
the use of neuroendoscopy are reviewed, including our clinical data. The major
significance of keyhole approach is to expose an essential space toward a target,
and to minimize brain exposure and retraction. Among several kinds of keyhole
approaches, representative keyhole approaches for anterior circulation aneurysms
include superciliary and lateral supraorbital, frontolateral, mini-pterional and
mini-interhemispheric approaches. Because only a fixed and limited approach angle
toward a target is permitted via the keyhole, however, specialized surgical
devices and preoperative planning are very important. Neuroendoscopy has helped
to widen the indications of keyhole approaches because it can supply illumination
and visualization of structures beyond the straight line of microscopic view. In
addition, endoscopic indocyanine green fluorescence angiography is useful to
detect and correct any compromise of the perforators and parent arteries, and
incomplete clipping. The authors think that keyhole approach and neuroendoscopy
are just an intermediate step and robotic neurosurgery would be realized in the
near future.
PMID- 28490153
TI - Prevention of Complications in Endoscopic Third Ventriculostomy.
AB - A variety of complications in endoscopic third ventriculostomy have been
reported, including neurovascular injury, hemodynamic alterations, endocrinologic
abnormalities, electrolyte imbalances, cerebrospinal fluid leakage, fever and
infection. Even though most complications are transient, the overall rate of
permanent morbidity is 2.38% and the overall mortality rate is 0.28%. To avoid
these serious complications, we should keep in mind potential complications and
how to prevent them. Proper decisions with regard to surgical indication, choice
of endoscopic entry and trajectory, careful endoscopic procedures with anatomic
orientation, bleeding control and tight closure are emphasized for the prevention
of complications.
PMID- 28490154
TI - From Exoscope into the Next Generation.
AB - An exoscope, high-definition video telescope operating monitor system to perform
microsurgery has recently been proposed an alternative to the operating
microscope. It enables surgeons to complete the operation assistance by
visualizing magnified images on a display. The strong points of exoscope are the
wide field of view and deep focus. It minimized the need for repositioning and
refocusing during the procedure. On the other hand, limitation of magnifying
object was an emphasizing weak point. The procedures are performed under 2D
motion images with a visual perception through dynamic cue and stereoscopically
viewing corresponding to the motion parallax. Nevertheless, stereopsis is
required to improve hand and eye coordination for high precision works.
Consequently novel 3D high-definition operating scopes with various mechanical
designs have been developed according to recent high-tech innovations in a
digital surgical technology. It will set the stage for the next generation in
digital image based neurosurgery.
PMID- 28490155
TI - Endoscopic Treatment of Hypothalamic Hamartomas.
AB - Hypothalamic hamartoma (HH) is a benign indolent lesion despite the presentation
of refractory epilepsy. Behavioral disturbances and endocrine problems are
additional critical symptoms that arise along with HHs. Due to its nature of
generating epileptiform discharge and spreading to cortical region, various
management strategies have been proposed and combined. Surgical approaches with
open craniotomy or endoscopy, stereotactic approaches with radiosurgery and gamma
knife surgery or radiofrequency thermos-coagulation, and laser ablation have been
introduced. Topographical dimension and the surgeon's preference are key factors
for treatment modalities. Endoscopic disconnection has been one of the most
favorable options performed in treating HHs. Here we discuss presurgical
evaluation, patient selection, surgical procedures, and complications.
PMID- 28490156
TI - Multiloculated Hydrocephalus: Open Craniotomy or Endoscopy?
AB - Multiloculated hydrocephalus (MLH) is a condition in which patients have
multiple, separate abnormal cerebrospinal fluid collections with no communication
between them. Despite technical advancements in pediatric neurosurgery,
neurological outcomes are poor in these patients and the approach to this
pathology remains problematic especially given individual anatomic complexity and
cerebrospinal fluid (CSF) hydrodynamics. A uniform surgical strategy has not yet
been developed. Current treatment options for MLH are microsurgical fenestration
of separate compartments by open craniotomy or endoscopy, shunt surgery in which
multiple catheters are placed in the compartments, and combinations of these
modalities. Craniotomy for fenestration allows better visualization of the
compartments and membranes, and it can offer easy fenestration or excision of
membranes and wide communication of cystic compartments. Hemostasis is more
easily achieved. However, because of profound loss of CSF during surgery, open
craniotomy is associated with an increased chance of subdural hygroma and/or
hematoma collection and shunt malfunction. Endoscopy has advantages such as
minimal invasiveness, avoidance of brain retraction, less blood loss, faster
operation time, and shorter hospital stay. Disadvantages are also similar to
those of open craniotomy. Intraoperative bleeding can usually be easily managed
by irrigation or coagulation. However, handling of significant intraoperative
bleeding is not as easy. Currently, endoscopic fenestration tends to be performed
more often as initial treatment and open craniotomy may be useful in patients
requiring repeated endoscopic procedures.
PMID- 28490157
TI - Endoscopic Third Ventriculostomy: Success and Failure.
AB - Endoscopic third ventriculostomy (ETV) has now become an accepted mode of
hydrocephalus treatment in children. Varying degrees of success for the procedure
have been reported depending on the type and etiology of hydrocephalus, age of
the patient and certain technical parameters. Review of these factors for
predictability of success, complications and validation of success score is
presented.
PMID- 28490158
TI - Endoscopic Endonasal Approach for Suprasellar Lesions in Children: Complications
and Prevention.
AB - The endoscopic endonasal approach (EEA) has been popularized in adults and has
been applied to an expanding range of surgical modules and indications in this
population. However, its clinical application in pediatric neurosurgery has been
impeded by the differences in anatomical features and the relatively low
incidence of diseases to which it is applicable. In this review article, we
mainly discuss the surgical indications, feasibility, and complications of EEA
for suprasellar lesions in children based on a review of the literature, focusing
especially on the age-related anatomical features of the nasal cavity, various
pathologic entities, and the impact of EEA on long-term craniofacial growth.
PMID- 28490159
TI - Neuroendoscopy: Current and Future Perspectives.
AB - Neuroendoscopic surgery is performed because it causes minimal damage to normal
structures, carries a lower rate of complications, and achieves excellent
outcomes. Surgeons using an endoscope and related instruments can perform complex
operations through very small incisions, which is especially useful for minimally
invasive procedures for the brain and spine. Neuroendoscopic surgery is now
performed in cases of obstructive hydrocephalus, various intraventricular
lesions, hypothalamic hamartomas, craniosynostosis, skull base tumors, and spinal
lesions. This review discusses the brief history of neuroendoscopy and the
current state and future perspectives of endoscopic surgery.
PMID- 28490160
TI - Transcortical Endoscopic Surgery for Intraventricular Lesions.
AB - To review recent advances in endoscopic techniques for treating intraventricular
lesions via transcortical passage. Articles in PubMed published since 2000 were
searched using the keywords 'endoscopy,' 'endoscopic,' and 'neuroendoscopic.' Of
these articles, those describing intraventricular lesions were reviewed.
Suprasellar arachnoid cysts (SACs) can be treated with ventriculo-cystostomy (VC)
or ventriculo-cysto-cisternostomy (VCC). VCC showed better results compared to
VC. Procedure type, fenestration size, stent placement, and aqueductal patency
may affect SAC prognosis. Colloid cysts can be managed using a transforaminal
approach (TA) or a transforaminal-transchoroidal approach (TTA). However, TTA may
result in better exposure compared to TA. Intraventricular cysticercosis can be
cured with an endoscopic procedure alone, but if pericystic inflammation and/or
ependymal reaction are seen, third ventriculostomy may be recommended. Tumor
biopsies have yielded successful diagnosis rates of up to 100%, but tumor
location, total specimen size, endoscope type, and vigorous coagulation on the
tumor surface may affect diagnostic accuracy. An ideal indication for tumor
excision is a small tumor with friable consistency and little vascularity. Tumor
size, composition, and vascularity may influence a complete resection. SACs and
intraventricular cysticercosis can be treated successfully using endoscopic
procedures. Endoscopic procedures may represent an alternative to surgical
options for colloid cyst removal. Solid tumors can be safely biopsied using
endoscopic techniques, but endoscopy for tumor resection still results in
considerable challenges.
PMID- 28490161
TI - Endovascular Stroke Therapy Focused on Stent Retriever Thrombectomy and Direct
Clot Aspiration: Historical Review and Modern Application.
AB - Intravenous recombinant tissue plasminogen activator had been the only approved
treatment for acute ischemic stroke since its approval in 1995. However, the
restrictive time window, numerous contraindications, and its low recanalization
rate were all limitations of this modality. Under those circumstances,
endovascular stroke therapy went through a great evolution during the past two
decades of intravenous thrombolysis. The results of the 2013 randomized trials
for endovascular stroke therapy were neutral, although they were limited by
insufficient imaging screening at enrollment, early-generation devices with less
efficacy, and treatment delays. Huge progress was made in 2015, as there were
five randomized clinical trials which all demonstrated the safety and efficacy of
endovascular stroke treatment. Despite differences in detail patient enrollment
criteria, all 5 trials employed key factors for good functional recovery; (1)
screening with non-invasive imaging to identify the proximal occlusion and
exclude a large infarct core, (2) using highly effective modern thrombectomy
devices mainly with stent retriever, and (3) establishment of a fast workflow to
achieve effective reperfusion. The results of those trials indicate that modern
thrombectomy devices can allow for faster and more effective reperfusion, which
can lead to improved clinical outcomes compared to intravenous thrombolysis
alone. These advances in mechanical thrombectomy are promising in the global
fight against ischemic stroke-related disability and mortality. Two current
mainstreams among such mechanical thrombectomy techniques, "stent retriever
thrombectomy" and "direct clot aspiration", are the topic of this review. Stent
retriever thrombectomy using Solitaire and Trevo retriever will be firstly
discussed. And, the commonalities and the differences between two major clot
aspiration thrombectomy techniques; a direct aspiration first pass technique
(ADAPT) and forced arterial suction thrombectomy (FAST), will be additionally
explained. Finally, details regarding the combination of direct clot aspiration
and stent retriever thrombectomy, the switching strategy and the Solumbra
technique, will be described.
PMID- 28490162
TI - Difference in Spinal Fusion Process in Osteopenic and Nonosteopenic Living Rat
Models Using Serial Microcomputed Tomography.
AB - OBJECTIVE: To identify and investigate differences in spinal fusion between the
normal and osteopenic spine in a rat model. METHODS: Female Sprague Dawley rats
underwent either an ovariectomy (OVX) or sham operation and were randomized into
two groups: non-OVX group and OVX group. Eight weeks after OVX, unilateral lumbar
spinal fusion was performed using autologous iliac bone. Bone density (BD) was
measured 2 days and 8 weeks after fusion surgery. Microcomputed tomography was
used to evaluate the process of bone fusion every two weeks for 8 weeks after
fusion surgery. The fusion rate, fusion process, and bone volume parameters of
fusion bed were compared between the two groups. RESULTS: BD was significantly
higher in the non-OVX group than in the OVX group 2 days and 8 weeks after fusion
surgery. The fusion rate in the non-OVX group was higher than that in the OVX
group 8 weeks after surgery (p=0.044). The bony connection of bone fragments with
transverse processes and bone formation between transverse processes in non-OVX
group were significantly superior to those of OVX group from 6 weeks after fusion
surgery. The compactness and bone maturation of fusion bed in non-OVX were
prominent compared with the non-OVX group. CONCLUSION: The fusion rate in OVX
group was inferior to non-OVX group at late stage after fusion surgery. Bone
maturation of fusion bed in the OVX group was inferior compared with the non-OVX
group. Fusion enhancement strategies at early stage may be needed to patients
with osteoporosis who need spine fusion surgery.
PMID- 28490164
TI - Contralateral Superior Cerebellar Artery Syndrome: A Consequence of Brain
Herniation.
AB - Vascular compromise is a well-known consequence of brain herniation syndromes.
Transtentorial brain herniation most often involves posterior cerebral arteries.
However, isolated involvement of contralateral superior cerebellar artery (SCA)
during unilateral impending brain herniation is reported only once and we present
another case of this exceedingly rare entity. A 24-year-old man was referred to
us with impending herniation due to a multiloculated hydrocephalus, and during
the course of illness, he developed an isolated SCA ischemia in the opposite side
of the most dilated entrapped horn. In the current article we discuss the
probable pathophysiologic mechanisms of this phenomenon, as well as recommending
more inclusive brain studies in cases suspected of Kernohan-Woltman notch
phenomenon in unilateral brain herniation. The rationale for this commentary is
that contralateral SCA transient ischemia or infarct might be the underdiagnosed
underlying pathomechanism of ipsilateral hemiparesis occurring in many cases of
this somehow vague phenomenon.
PMID- 28490163
TI - Effects of Quercetin and Mannitol on Erythropoietin Levels in Rats Following
Acute Severe Traumatic Brain Injury.
AB - OBJECTIVE: The aim of this study to investigate the normal values of
erythropoietin (EPO) and neuroprotective effects of quercetin and mannitol on EPO
and hematocrit levels after acute severe traumatic brain injury (TBI) in rat
model. METHODS: A weight-drop impact acceleration model of TBI was used on 40
male Wistar rats. The animals were divided into sham (group I), TBI (group II),
TBI+quercetin (50 mg/kg intravenously) (group III), and TBI+mannitol (1 mg/kg
intravenously) (group IV) groups. The malondialdehyde, glutathione peroxidase,
catalase, EPO, and hematocrit levels were measured 1 and 4 hour after injury. Two
way repeated measures analysis of variance and Tukey's test were used for
statistical analysis. RESULTS: The malondialdehyde levels decreased significantly
after administration of quercetin and mannitol compared with those in group II.
Catalase and glutathione peroxidase levels increased significantly in groups III
and IV. Serum EPO levels decreased significantly after mannitol but not after
quercetin administration. Serum hematocrit levels did not change significantly
after quercetin and mannitol administration 1 hour after trauma. However,
mannitol administration decreased serum hematocrit levels significantly after 4
hour. CONCLUSION: This study suggests that quercetin may be a good alternative
treatment for TBI, as it did not decrease the EPO levels.
PMID- 28490165
TI - Remote Cerebellar Hemorrhage Presenting with Cerebellar Mutism after Spinal
Surgery: An Unusual Case Report.
AB - Dural injury during spinal surgery can subsequently give rise to a remote
cerebellar hemorrhage (RCH). Although the incidence of such injury is low, the
resulting hemorrhage can be life threatening. The mechanism underlying the
formation of the hemorrhage is not known, but it is mostly thought to develop
after venous infarction. Cerebellar mutism (CM) is a frequent complication of
posterior fossa operations in children, but it is rarely seen in adults. The
development of CM after an RCH has not been described. We describe the case of a
65-year old female who lost cerebrospinal fluid after inadvertent opening of the
dura during surgery. Computerized tomography performed when the patient became
unable to speak revealed a bilateral cerebellar hemorrhage.
PMID- 28490166
TI - Giant Ganglioneuroma of Thoracic Spine: A Case Report and Review of Literature.
AB - Ganglioneuroma (GN) is a rare benign tumor of neural crest origin usually found
in the abdomen, but may occasionally present at uncommon sites including the
cervical, lumbar, or sacral spine. However, GNs of thoracic spine are extremely
rare. In this report, we describe a 12-year-old girl with giant GN in the
thoracic spine, who underwent successful resection (T1-4 level) of the tumor.
Histopathological examination confirmed the diagnosis. GN should be considered in
the differential diagnosis of any paraspinal mass. A high index of suspicion and
correlation of clinico-radiological findings is necessary in differentiating a
large benign tumor from a malignant growth. Complete surgical excision is the
treatment of choice; however tumor size and location need to be considered for
the surgical approach (one-step or multiple surgeries). Close follow-up after
surgery is mandatory.
PMID- 28490167
TI - Endoscopic Treatment of an Adult with Tegmental Astrocytoma Accompanied by
Cerebrospinal Fluid Dissemination.
AB - Midbrain gliomas are relatively rare neoplasms with a generally benign prognosis,
with dissemination or metastasis not previously reported. We describe here a
woman, in whom magnetic resonance imaging scans showed hydrocephalus and a
tegmental lesion in the upper aqueduct. Endoscopic third ventriculostomy and
biopsy were performed; during surgery, a second small lesion was observed in the
infundibular recess. Histologically, the two lesions had the characteristics of
low grade astrocytoma, suggesting that the midbrain astrocytoma may have been
disseminated via the cerebral spinal fluid to the infundibular recess.
Postoperatively this patient received radiotherapy for nearly one month. Although
patients with these tumors are not usually administered adjunctive therapy,
radiation and, combined modality therapy, including surgery, radiotherapy, and
chemotherapy, may be beneficial in patients with midbrain gliomas with
dissemination.
PMID- 28490168
TI - Primary Glioblastoma of the Cerebellopontine Angle: Case Report and Review of the
Literature.
AB - Glioblastoma multiforme (GBM) is located most frequently in the cerebral
hemispheres. Glioblastoma presenting as an extraaxial mass of cerebellopontine
angle (CPA) is very rare in adults. We report a rare case of GBM arising in the
CPA. The patient was a 71-year-old female, who complained of progressive gait
disturbance and poor memory. Initial magnetic resonance imaging (MRI) revealed a
1.4*1.3 cm mass in the left CPA, with broad base to the petrous bone, showing
homogenous enhancement. Follow-up MRI showed a rapid increase in size of mass
(2.7*2.2 cm) with a necrotic portion. A stereotactic biopsy was done under the
guidance of navigation system, and the histopathologic diagnosis was GBM, World
Heath Organization grade IV. Further surgical resection was not performed
considering her general condition, and the patient underwent concurrent
chemotherapy with radiation therapy. Although rare, the possibility of
glioblastoma should be included in the differential diagnosis of atypical CPA
tumor.
PMID- 28490169
TI - Ethical considerations in the field of assisted reproductive technology.
AB - Human reproduction has always generated more than its share of emotion that
exceeds the life and death issues of medicine. For patients that are unable to
conceive naturally, medical advances have greatly expanded treatment options.
Assisted reproductive technology (ART) is a highly evolving, complex, and
controversial field of medicine in which ethical principles play a large role in
decision-making. The following highlights ethical considerations regarding ART,
specifically in vitro fertilization (IVF), that practicing obstetricians and
indeed all physicians may encounter. The aim was to encourage practitioners to
consider these issues, and more, when developing guidelines for their own
practice.
PMID- 28490170
TI - Fertility preservation for social and oncofertility indications.
AB - The desire to reproduce is a base human instinct. However, for many individuals,
the chances of being able to have a genetic child are compromised by a number of
factors. For some, therapies aimed at treating serious medical illness, such as
cancer; result in a deleterious impact on the function of eggs and sperm in the
future thus compromising future fertility. In women, a predictable decrease in
egg quality and quantity occurs with advancing maternal age. Therefore, women who
choose to delay childbearing until their late 30s or early 40s may experience
fertility difficulties that would not have been present earlier in life.
Currently, technologies exist that allow individuals to have an "insurance
policy" to preserve eggs or sperm prior to being exposed to agents, including
time or specific toxic agents to the ovaries or sperm, that may decrease
fertility potential. This article attempts to summarize the current state of the
art technologies regarding fertility preservation for both social and
oncofertility indications.
PMID- 28490171
TI - Management of perforation following stricture dilation.
AB - Strictures can occur along any portions of the gastrointestinal tract for a
variety of reasons and are commonly complicated by partial or complete
obstruction. Endoscopic management of strictures is common, and generally safe.
The most dreaded complication of stricture dilation is perforation due to high
morbidity and mortality. The treatment of perforation following stricture
dilation is commonly multidisciplinary and should involve gastrointestinal,
surgical, and interventional radiology teams. A variety of devices and techniques
are available to the endoscopist which now allow for successful endoscopic
management of perforation in many cases.
PMID- 28490172
TI - Antiviral Activities of Trichothecenes Isolated from Trichoderma albolutescens
against Pepper Mottle Virus.
AB - A bioassay-guided isolation using a green fluorescence protein (GFP)-tagged
pepper mottle virus (PepMoV-GFP) based leaf-disk method to obtain new antiviral
agents led to the isolation of trichodermin, 1, and a new compound
trichoderminol, 2, from EtOAc extract of Trichoderma albolutescens culture
medium. The structures of compounds 1 and 2 were determined by MS and NMR
experiments, and the absolute configurations of the compounds were established by
experimental and calculated vibrational circular dichroism spectra. Compounds 1
and 2 were evaluated for their anti-PepMoV potential in systemic host plants,
such as tobacco and pepper, by PepMoV-GFP based systemic host method. All
compounds exhibited inactivation effects against PepMoV. Furthermore, compound 1
showed protective effects against PepMoV.
PMID- 28490173
TI - Applying Cadmium Relative Bioavailability to Assess Dietary Intake from Rice to
Predict Cadmium Urinary Excretion in Nonsmokers.
AB - Dietary Cd intake is often estimated without considering Cd bioavailability.
Measured urinary Cd for a cohort of 119 nonsmokers with rice as a staple was
compared to predicted values from rice-Cd intake with and without considering Cd
relative bioavailability (RBA) in rice based on a steady state mouse kidney
bioassay and toxicokinetic model. The geometric mean (GM) of urinary Cd and beta2
microglobulin was 1.08 and 234 MUg g-1 creatinine. Applying Cd-RBA in foods to
aggregate Cd intake (41.5 +/- 12.4, 48.0 +/- 9.3, 48.8 +/- 21.3% for rice, wheat,
and vegetables), rice was the largest contributor (71%). For 63 participants
providing paired urine and rice samples, the predicted GM of urinary Cd at 4.14
MUg g-1 based on total Cd in rice was 3.5 times that of measured value at 1.20
MUg g-1, while incorporating Cd-RBA to assess rice-Cd intake made the two closer
with GM at 1.07 MUg g-1. The cohort findings were extended to a national scale,
with urinary Cd for nonsmokers from rice Cd intake was mapped at province/city
levels after considering rice Cd-RBA. Therefore, incorporating Cd bioavailability
to assess dietary Cd intake is a valuable tool to accurately estimate human Cd
exposure and associated health risk.
PMID- 28490174
TI - Self-Organization of Electroactive Suspensions in Discharging Slurry Batteries: A
Mesoscale Modeling Investigation.
AB - We report a comprehensive modeling-based study of electroactive suspensions in
slurry redox flow batteries undergoing discharge. A three-dimensional kinetic
Monte Carlo model based on the variable step size method is used to describe the
electrochemical discharge of a silicon/carbon slurry electrode in static mode
(i.e., no fluid flow conditions). The model accounts for Brownian motion of
particles, volume expansion of silicon upon lithium insertion, and formation and
destruction of conducting carbon networks. Coupled to an electrochemical model,
this study explores the impact of carbon fraction in the slurry and applied c
rate on the specific capacity. The trends obtained are analyzed by following the
behavior of parameters such as number of contacts between electroactive particles
and the percentage of electroactive silicon particles. Furthermore, instead of
studying the bulk behavior of the slurry, here the focus is given to the
slurry/current collector interface in order to illustrate its importance. Hereby,
it is demonstrated how this modeling tool can lead to deeper understanding and
optimization of electroactive particle suspensions in redox flow batteries.
PMID- 28490176
TI - Conformation of Ethylene Glycol in the Liquid State: Intra- versus Intermolecular
Interactions.
AB - Ethylene glycol is a typical rotor molecule with the three dihedral angles that
allow for a number of possible conformers. The geometry of the molecule in the
liquid state brings into sharp focus the competition between intra- and inter
molecular interactions in deciding conformation. Here, we report a conformational
analysis of ethylene glycol in the liquid state from ab initio molecular dynamics
simulations. Our results highlight the importance of intermolecular hydrogen
bonding over intramolecular interactions in the liquid, with the central OCCO
linkage adopting both gauche and trans geometries in contrast to the gas phase,
wherein only the gauche has been reported. The influence of intermolecular
interactions on the conformation of the terminal CCOH moieties is even more
striking, with certain regions of conformational space, wherein the ethylene
glycol molecule cannot participate with its full complement of intermolecular
hydrogen bonds, excluded. The results are in agreement with Raman and NMR
spectroscopic studies of liquid ethylene glycol, but at the same time they are
able to provide new insights into how intermolecular interactions favor certain
conformations while excluding others.
PMID- 28490175
TI - Prenatal Nonylphenol and Bisphenol A Exposures and Inflammation Are Determinants
of Oxidative/Nitrative Stress: A Taiwanese Cohort Study.
AB - Prenatal exposure to nonylphenol (NP) and/or bisphenol A (BPA) has been reported
to be associated with adverse birth outcomes; however, the underlying mechanisms
remain unclear. The primary mechanism is endocrine disruption of the binding
affinity for the estrogen receptor, but oxidative stress and inflammation might
also play a contributory role. We aimed to investigate urinary NP and BPA levels
in relation to biomarkers of oxidative/nitrative stress and inflammation and to
explore whether changes in oxidative/nitrative stress are a function of prenatal
exposure to NP/BPA and inflammation in 241 mother-fetus pairs. Third-trimester
urinary biomarkers of oxidative/nitrative stress were simultaneously measured,
including products of oxidatively and nitratively damaged DNA (8-hydroxy-2'
deoxyguanosine (8-OHdG) and 8-nitroguanine (8-NO2Gua)) as well as products of
lipid peroxidation (8-iso-prostaglandin F2alpha (8-isoPF2alpha) and 4-hydroxy-2
nonenal-mercapturic acid (HNE-MA)). The antioxidant glutathione peroxidase (GPx)
and inflammation biomarkers, including C-reactive protein (CRP) and a panel of
cytokines (interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha)),
were analyzed in maternal and umbilical cord plasma samples. In adjusted models,
we observed significant positive associations between NP exposure and 8-OHdG and
8-NO2Gua levels, between BPA and 8-isoPF2alpha levels, and between maternal CRP
levels and HNE-MA levels. Additionally, BPA and TNF-alpha levels in cord blood
were inversely associated with maternal and GPx levels in cord blood as well as
maternal TNF-alpha levels were inversely associated with maternal GPx levels.
These results support a role for exposure to NP and BPA and possibly inflammation
in increasing oxidative/nitrative stress and decreasing antioxidant activity
during pregnancy.
PMID- 28490177
TI - Synthesis of alpha-l-Threofuranosyl Nucleoside 3'-Monophosphates, 3'-Phosphoro(2
Methyl)imidazolides, and 3'-Triphosphates.
AB - alpha-l-Threofuranosyl nucleic acid (TNA) is an artificial genetic polymer
composed of vicinal 2',3'-phosphodiester bonds linking adjacent threofuranosyl
nucleosides. TNA is one of a small number of genetic polymers that are both
highly resistant to nuclease digestion and capable of cross-pairing with DNA and
RNA. Although an efficient method for synthesizing TNA nucleosides has been
reported, very few advances have been made in the synthesis of phosphorylated TNA
compounds. Here, we describe a highly efficient method for synthesizing alpha-l
threofuranosyl nucleoside 3'-monophosphates (tNMPs), 3'-phosphoro(2
methyl)imidazolides (2-MeImptNs), and 3'-triphosphates (tNTPs) bearing the four
genetic bases of adenine (A), cytosine (C), thymine (T), and guanine (G). We
suggest that this strategy, which provides access to grams of tNMPs, hundreds of
milligrams of 2-MeImptNs, and tens of milligrams of tNTPs, will help advance the
use of TNA monomers in exobiology and biotechnology applications.
PMID- 28490178
TI - Atom Tunneling in the Hydroxylation Process of Taurine/alpha-Ketoglutarate
Dioxygenase Identified by Quantum Mechanics/Molecular Mechanics Simulations.
AB - Taurine/alpha-ketoglutarate dioxygenase is one of the most studied alpha
ketoglutarate-dependent dioxygenases (alphaKGDs), involved in several
biotechnological applications. We investigated the key step in the catalytic
cycle of the alphaKGDs, the hydrogen transfer process, by a quantum
mechanics/molecular mechanics approach (B3LYP/CHARMM22). Analysis of the charge
and spin densities during the reaction demonstrates that a concerted mechanism
takes place, where the H atom transfer happens simultaneously with the electron
transfer from taurine to the Fe?O cofactor. We found the quantum tunneling of the
hydrogen atom to increase the rate constant by a factor of 40 at 5 degrees C. As
a consequence, a quite high kinetic isotope effect close to 60 is obtained, which
is consistent with the experimental value.
PMID- 28490179
TI - "Living" dynamics of filamentous bacteria on an adherent surface under
hydrodynamic exposure.
AB - The potential advantages of cell-based biohybrid devices over conventional
nonliving systems drive the interest to control the behavior of the underlying
biological cells in microdevices. Here, the authors studied how shear influenced
the geometry and elongation of fimbriated filaments on affinity substrates. The
cells were engineered to express FimH, which binds to mannose with a high
affinity. A microfluidic channel was functionalized with RNAse B, which is rich
in mannose residues, and the device was used to control the hydrodynamic force on
live Escherichia coli under filamentous growth. It was discovered that
filamentous E. coli cells adopt buckled geometry when the shear rate is low, but
assume an extended geometry at high shear and align with the flow direction. The
extension moves from bidirectional to preferentially downstream as the shear rate
increases. Furthermore, living filaments slide easily on the substrate, and
detach from the substrates at a rate nearly ten times greater than unfilamented
live E. coli at high shear conditions (1000-4000 s-1). The hydrodynamic force and
binding force experienced by the cells are further analyzed by COMSOL simulation
and atomic force microscopy measurements, respectively, to explore the mechanism
behind the living cell dynamics. Knowledge from this work helps guide design of
interfacial properties and shear environments to control the geometry of living
filamentous bacteria.
PMID- 28490180
TI - "Category 4A" microcalcifications: how should this subcategory be applied to
microcalcifications seen on mammography?
AB - Background The BI-RADS provides descriptors for microcalcifications based on
morphology and distribution. However, the descriptor for category 4A
microcalcifications is not specified in the 5th BI-RADS nor in the prior
editions. Purpose To investigate how the category 4A assessment is applied to
suspicious microcalcifications, and the appropriate descriptors for category 4A
assessment for microcalcifications seen on mammography. Material and Methods From
June 2008 to November 2011, 296 women with 305 suspicious microcalcifications
that were assessed as BI-RADS category 4A, who underwent imaging-guided biopsy or
surgery, were included. Mammograms were reviewed and imaging features were
analyzed according to the morphology and distribution descriptors of the 5th
edition of BI-RADS. Pathological results were considered as the reference
standard. Positive predictive values were calculated and compared between
morphology and distribution descriptors. Results The overall positive predictive
value (PPV) of category 4A microcalcifications was 17.7% (54/305). Most common
descriptors for category 4A microcalcifications were amorphous morphology (73.1%)
and grouped distribution (71.1%). PPVs of individual morphology descriptors were
as follows: amorphous = 7.2%; coarse heterogeneous = 12.8%; fine pleomorphic or
fine linear/fine linear branching = 91.4% ( P < 0.001). PPVs of distribution
descriptors were as follows: regional = 13.2%; grouped = 16.1%; linear/segmental
= 54.5% ( P < 0.001). For morphology and distribution descriptors combinations,
PPVs for amorphous/regional and amorphous/grouped microcalcifications were 6.8%
and 6.9%, while PPVs of other combinations were higher than 10%, respectively.
Conclusion Common descriptors used in category 4A assessment for
microcalcifications are amorphous morphology and grouped distribution. PPV of
amorphous/regional and amorphous/grouped microcalcifications were suitable for
category 4A assessment.
PMID- 28490181
TI - Designing and evaluating autoverification rules for thyroid function profiles and
sex hormone tests.
AB - Purpose Following the analytical phase, the current practice of many hospital
laboratories involves the manual verification of all test results followed by the
production of the report. However, manual verification is a time-consuming and
tedious process. In this paper, we provide a detailed description of how to
design autoverification rules for thyroid function test profiles and sex
hormones. Materials and methods We used DM2 (Data manager 2) to construct the
algorithm and build the database for autoverification of thyroid function test
profiles and sex hormones, with reference to Boolean logic, Auto 10-A and
CLSI'88. The rules consist of checking quality control, instrument error flags,
critical values, the analytical measurement range (AMR), the limit range,
consistency check and delta check. Firstly, we established the rules in the DM2,
collected clinical specimens for validation, then tested the rules in a 'live'
environment. Results Agreement was achieved between manual verification by two
senior laboratory personnel and verification using the autoverification rules in
99.78% of the cases. The total autoverification rate for all tests was 77.06%.
Following implementation of the rules, the laboratory turnaround time (TAT) was
reduced by 54.55% and staffing numbers fell from three to two whole time
equivalents (WTE). Statistical analysis resulted in a kappa statistic of 0.99 ( P
< 0.001). Moreover, after implementing the autoverification rules, the error rate
fell to 0.04%, indicating that errors were almost completely eliminated.
Conclusion Implementing autoverification rules can reduce TAT, minimize the
number of samples that require manual verification and allow for a reduction in
staffing numbers. It also allows laboratory staff to devote more time and effort
to the handling of problematic test results and contributing to improved patient
care.
PMID- 28490182
TI - Multiple myeloma and acquired von Willebrand disease: a combined cause of
preanalytical interference causing gel formation?
AB - We report a patient with acquired von Willebrand disease, associated with
multiple myeloma. At one stage in his illness, we were unable to analyse a sample
sent in a serum separator tube, due to the presence of a gel within the separated
serum layer. We suggest this was due to anomalous position of the gel because of
the density of the sample caused by its high total protein concentration,
exacerbated by fibrin strand formation because of inhibition of appropriate
fibrin clot formation secondary to clotting disorder.
PMID- 28490183
TI - Clinical utility of measuring both glutamic acid decarboxylase antibodies and
islet cell antibodies in the diagnosis of latent autoimmune diabetes in adults -
is it cost-effective?
PMID- 28490184
TI - Electrophoretic patterns post daratumumab.
AB - Background Daratumumab (Darzalex) is a human IgG1 kappa monoclonal antibody
targeting CD38 that has been recently approved for the treatment of refractory
multiple myeloma. As it is a monoclonal protein, it can be detected on routine
serum protein electrophoresis and by immunofixation. Methods Serum samples from
four patients were analysed by serum protein electrophoresis immediately pre- and
post-treatment with daratumumab. Results For all four patients, daratumumab was
visible on serum protein electrophoresis as an additional small band
(approximately 1 g/L) in the slow gamma region. Conclusion Diagnostic
laboratories should be aware that daratumumab can be detected on routine serum
protein electrophoresis of myeloma patients and should liaise closely with
clinicians to ensure the presence of daratumumab is not misinterpreted as
development of a new monoclonal protein.
PMID- 28490185
TI - Low dehydroepiandrosterone sulphate: a sensitive and specific test for the
detection of subclinical hypercortisolism in adrenal incidentalomas.
PMID- 28490186
TI - Two-dimensional quantitative structure-activity relationship study of 1,4
naphthoquinone derivatives tested against HL-60 human promyelocytic leukaemia
cells.
AB - A series of 50 derivatives of 1,4-naphthoquinone tested against human HL-60
leukaemic cells showed activity at a wide range of concentrations. A multivariate
quantitative structure-activity relationship (QSAR) study of 45 compounds was
performed through principal component analysis (PCA) and partial least squares
(PLS) regression. A good PLS regression model was obtained with two factors
describing 60.1% of the total variance, and the selected descriptors were partial
atomic charge at carbons 1 and 10 (C1 and C10) and total dipole moment (DIP). The
calibration model exhibited the determination coefficient r2 = 0.78 and the
standard error of calibration = 0.29. For external validation, r2 and the
standard error of prediction were 0.74 and 0.32, respectively. DIP and C1 were
the main descriptors for PCA, as well as for PLS, such that the pIC50 value
increases when C1 increases and DIP diminishes. The selected descriptors are in
accordance with the literature, once C10 and C1 are bound or close to the quinone
oxygens involved in the production of radical anions (O2-?). From the QSAR
analysis, the structures of two new naphthoquinones were proposed and their
estimated IC50 values were 1.42 and 1.13 MUmol L-1.
PMID- 28490187
TI - Episodic status migrainosus: One more case.
PMID- 28490188
TI - The retinal microcirculation in migraine: The Rotterdam Study.
AB - Background To explore the role of microvascular pathology in migraine, we
investigated the association between migraine and retinal microvascular damage.
Methods We included 3270 participants (age >= 45 years, 63% women) from the
population-based Rotterdam Study (2006-2009). Participants with migraine were
identified using a validated questionnaire based on ICHD-II criteria (n = 562).
Retinopathy signs were graded on fundus photographs. Retinal arteriolar and
venular caliber were measured by semi-automatic assessment of fundus photographs.
Associations of migraine with retinopathy and retinal microvascular calibers were
examined using logistic and linear regression models, respectively, adjusting for
age, sex, and cardiovascular risk factors. Results Migraine was not associated
with the presence of retinopathy (odds ratio (OR): 1.09, 95% confidence interval
(CI) 0.62; 1.92). In the fully adjusted model, adjusting for the companion
vessel, persons with migraine did not differ in retinal arteriolar or venular
caliber compared to persons without migraine (mean difference in standardized
arteriolar caliber -0.05 (95%CI -0.13; 0.03); in standardized venular caliber
0.00 (95%CI -0.09; 0.08)). Migraine subtypes, including migraine with aura, were
also not associated with retinal microvascular damage. Conclusions Our findings
suggest that migraine is not associated with retinopathy or difference in retinal
microvascular caliber. Further studies are needed to confirm these results.
PMID- 28490189
TI - Langerhans cell histiocytosis (eosinophilic granuloma) of the skull mimicking
nummular headache. Report of two cases.
AB - Background Nummular headache is a rare, recently described topographic headache
defined by the circumscribed coin-shaped area of pain. It is classified as a
primary headache. There is debate about whether it is due to a peripheral or
central disturbance, and its relationship to migraine. Case reports We report two
patients with presumed nummular headache secondary to Langerhans cell
histiocytosis, both with resolution of their headaches after surgical resection.
Conclusion Imaging in patients with clinical features of nummular headache is
recommended, as this and other cases highlight that it may be symptomatic. There
are no distinguishing clinical features to separate nummular headache from
secondary mimics, and treatment of the underlying cause may be curative.
PMID- 28490190
TI - Deployment-Related Traumatic Events and Suicidal Behaviours in a Nationally
Representative Sample of Canadian Armed Forces Personnel.
AB - OBJECTIVE: Worldwide, there has been substantial controversy with respect to
whether military deployment is a risk factor for suicidal behaviour. The present
study examined the relationship between lifetime exposure to deployment and
deployment-related traumatic events (DRTEs) and past-year suicidal ideation (SI),
suicidal plans (SP), and suicidal attempts (SA). METHOD: Data were analysed from
the 2013 Canadian Forces Mental Health Survey (8161 respondents; response rate,
79.8%; aged 18-60 years). A total of 12 individual items assessed exposure to
DRTEs (e.g., combat, witnessing human atrocities, feeling responsible for the
death of Canadian or ally personnel, knowing someone who was injured or killed).
We examined each individual DRTE type as well as the number of types of DRTEs in
relation to suicidal behaviour. RESULTS: Lifetime deployment was not
significantly associated with suicidal behaviour. In models adjusted for
sociodemographic variables, most of the individual DRTE items and the DRTE count
variable were significantly associated with suicidal behaviours (adjusted odds
ratio ranged between 1.10 and 5.32). When further adjusting for child abuse
exposure, these associations were minimally attenuated, and some became
nonsignificant. In models adjusting for mental disorders and child abuse, most
DRTEs and number of types of DRTEs became nonsignificant in relation to SI, SP,
and SA. CONCLUSIONS: Active military personnel exposed to increasing number of
DRTEs are at increased risk for SI, SP, and SA. However, most of the association
between DRTEs and suicidal behaviour is accounted for by child abuse exposure and
mental disorders.
PMID- 28490191
TI - Proliferative and antioxidant activity of Symphytum officinale root extract.
AB - The root of Symphytum officinale L. is commonly used in folk medicine to promote
the wound healing, reduce the inflammation and in the treatment of broken bones.
The objective of our investigation was to analyse the extract from S. officinale
in term of its antioxidant activity and the effect on cell viability and
proliferation of human skin fibroblast (HSF). Moreover, the quantification of
main phenolics and allantoin was conducted using HPLC-DAD method. Five compounds
were found: rosmarinic, p-hydroxybenzoic, caffeic, chlorogenic and p-coumaric
acid. DPPH, FRAP and TPC assay showed the high antioxidant activity of the
extract. MTT test proved the stimulatory effect on cell metabolism and viability
of HSF cells. Moreover, no changes in cytoskeleton structure and cells shape were
observed. The obtained results indicate that non-toxic extract from S. officinale
root has strong antioxidant potential and a beneficial effect on human skin
fibroblasts.
PMID- 28490192
TI - LTX-315: a first-in-class oncolytic peptide that reprograms the tumor
microenvironment.
AB - The oncolytic peptide LTX-315, which has been de novo designed based on structure
activity relationship studies of host defense peptides, has the ability to kill
human cancer cells and induce specific anticancer immune response when injected
locally into tumors established in immunocompetent mice. The oncolytic effect of
LTX-315 involves perturbation of plasma membrane and the mitochondria with
subsequent release of danger-associated molecular pattern molecules, which
highlights the ability of LTX-315 to induce complete regression and protective
immune responses. Treatment with LTX-315 reprograms the tumor microenvironment by
decreasing the local abundance of immunosuppressive cells and by increasing the
frequency of effector T cells.
PMID- 28490193
TI - Aminoisoquinoline benzamides, FLT3 and Src-family kinase inhibitors, potently
inhibit proliferation of acute myeloid leukemia cell lines.
AB - AIM: Mutated or overexpressed FLT3 drives about 30% of reported acute myeloid
leukemia (AML). Currently, FLT3 inhibitors have shown durable clinical responses
but a complete remission of AML with FLT3 inhibitors remains elusive due to
mutation-driven resistance mechanisms. The development of FLT3 inhibitors that
also target other downstream oncogenic kinases may combat the resistance
mechanism. RESULTS: 4-substituted aminoisoquinoline benzamides potently inhibit
Src-family kinases and FLT3, including secondary mutations, such as FLT3D835.
Modifications of aminoisoquinoline benzamide to aminoquinoline or
aminoquinazoline abrogated FLT3 and Src-family kinase binding. CONCLUSION: The
lead aminoisoquinolines potently inhibited FLT3-driven AML cell lines, MV4-11 and
MOLM-14. These aminoisoquinoline benzamides represent new kinase scaffolds with
high potential to be translated into anticancer agents.
PMID- 28490194
TI - Prepulse Inhibition of the Auditory Off-Response: A Magnetoencephalographic
Study.
AB - A weak preceding sound stimulus attenuates the startle response evoked by an
intense sound stimulus. Like startle reflexes, change-related auditory responses
are suppressed by a weak leading stimulus (ie, a prepulse). We aim to examine
whether a prepulse inhibits cerebral responses to the sound offset and how the
prepulse magnitude affects the degree of the prepulse inhibition (PPI). Using
magnetoencephalography, we recorded the Off-P50m elicited by an offset of a train
sound of 100-Hz clicks in 12 healthy subjects. A single click slightly louder
(+1.5, +3, or +5 dB) than the background sound of 80 dB was inserted 50 ms before
the sound offset as a prepulse. We performed a dipole source analysis of the Off
P50m, and we measured its latency and amplitude using the source strength
waveforms. The origin of the Off-P50m was estimated to be the auditory cortex on
both hemispheres. The Off-P50m was clearly attenuated by the prepulses, and the
degree of PPI was greater with a louder prepulse. The Off-P50m is considered to
be a simple change-related response, which does not overlap with a processing of
incoming sounds. Thus, the Off-P50m and its PPI comprise a valuable tool for
investigating the neural inhibitory system.
PMID- 28490195
TI - The Takei Handheld Dynamometer: An Effective Clinical Outcome Measure Tool for
Hand and Wrist Function in Boxing.
AB - BACKGROUND: The aim of this article was to explore retrospectively the Takei
dynamometer as a valid and reliable outcome measure tool for hand and wrist
pathology in the Great Britain amateur boxing squad between 2010 and 2014.
METHODS: Longitudinal retrospective injury surveillance of the Great Britain
boxing squad was performed from 2010 to 2014. The location, region affected,
description, and duration of each injury were recorded by the team doctor and
team physiotherapists. For each significant injury, we recorded hand grip scores
using the Takei handheld dynamometer and compared the scores with baseline
measures. RESULTS: At the hand, fractures and dislocations were highly detected
with an average difference of 40.2% ( P < .05) when comparing postinjury to
baseline measures. At the wrist, carpometacarpal and carpal joint injuries were
highly detected with an average difference of 32.6% ( P < .05). Other injuries
provided varied results. In the absence of pathology, up to 15% difference
between left and right scores can be considered normal with a predominance
observed below 10%. A difference of 20% can be indicative of a form of pathology,
although pathologies can also be present with lower difference or no apparent
changes. A difference of >20% should be highly considered for significant
pathology. CONCLUSIONS: The Takei dynamometer is a valid and reliable outcome
measure tool for hand and wrist pathologies in boxing. Our study highlights the
importance of appropriate clinical tools to guide injury management in this
sport.
PMID- 28490196
TI - Effectiveness of second-line antiretroviral therapy: the impact of drug switches.
AB - Including antiretroviral drug switches as a measure of ART failure could be more
suitable than conventional measures to evaluate health outcomes in "real-world"
settings. This is part of a historical cohort of HIV-infected adults who
initiated ART from 2001-2005, and were followed up for a maximum of five years in
three HIV/AIDS centers in Belo Horizonte, Brazil. Follow-up information included
data from 2001-2010. All patients switched from first-line ART were included.
Second-line ART effectiveness was measured as the time-to-ART failure. Failure
was defined simulating two scenarios: (1) Clinical, immunological and virological
failure (scenario 1); and scenario 1 plus ART switches (scenario 2). Descriptive
analysis, Kaplan-Meier curves, log-rank test, and Cox proportional hazards model
were performed. We identified 119 eligible patients; most had protease inhibitor
(PI)-based regimens prescribed as second-line. The incidence of failure was
different for the two scenarios (29.4% vs. 54.6% for scenario 1 and 2,
respectively; p < 0.001). The main identifiers of failure were increase in viral
load (31.1%) for scenario 1 and ART switches (42.8%) for scenario 2. Median
duration on second-line ART was 36.8 vs. 19.8 months for scenario 1 and 2,
respectively. In the Cox analysis of scenario 2, increased risk was found for
patients given PI-based second-line regimens (HR = 2.26; 95% CI: 1.09-3.17).
There is a high incidence of ART failure associated with PI-based regimens when
ART switches are considered as an indicator of failure. This demonstrates the
impact of ART switches in representing lack of ART effectiveness.
PMID- 28490197
TI - Psychological and behavioral barriers to ART adherence among PLWH in China: role
of self-efficacy.
AB - Globally, optimal adherence to antiretroviral therapy (ART) is insufficient
despite it is critical for maximum clinical benefits and treatment success among
people living with HIV (PLWH). Many factors have been evidenced to influence
medication adherence, including perceived barriers and self-efficacy. However,
limited data are available regarding to psychological and behavioral barriers to
ART adherence in China. Moreover, few studies have examined the mechanism of
these two factors underlying HIV medication adherence. The aim of the current
study is to examine the mediating role of adherence self-efficacy between
perceived barriers and ART adherence among PLWH. Cross-sectional data were
obtained from 2095 PLWH in Guangxi China who provided data on ART adherence.
Participants reported their medication adherence, self-efficacy, barriers to ART
adherence, as well as background characteristics. Results indicated a significant
indirect effect from perceived barriers to medication adherence through adherence
self-efficacy. Higher perceived psychological and behavioral barriers to ART
adherence were related to lower adherence self-efficacy, which in turn was
related to lower ART adherence. Self-efficacy could buffer the negative effects
of perceived barriers on ART adherence. Future interventions to promote HIV
medication adherence are recommended to focus on eliminating psychological and
behavioral barriers, as well as increasing adherence self-efficacy.
PMID- 28490198
TI - Drug-Induced Takotsubo Cardiomyopathy.
AB - BACKGROUND: The most plausible hypothesis for takotsubo cardiomyopathy (TCM) is a
catecholamine surge. Direct administration of catecholamines or medications
causing catecholamine surge is frequently used in clinical practice. METHODS: A
Medline/PubMed database search was conducted for case reports or series of drug
induced TCM. All reported cases of drug-induced TCM were systemically identified
and analyzed. RESULTS: We identified 157 cases of drug-induced TCM. Fifty-seven
(36.3%) cases were related to the administration of exogenous catecholamines. In
50 (31.9%) other cases, there was potential adrenergic effect. This included
drugs with adrenergic vasoconstriction properties (3.2%), hyperadrenergic state
due to alcohol or opioid withdrawal (7.7%), inhibitors of catecholamine reuptake
(14.7%), anaphylactic reaction that is accompanied by catecholamine release
(3.2%), and psychological or somatic stress coinciding with the administration of
a drug that was thought to be the culprit (3.2%). Overall, 68.2% of these drug
induced TCM cases were catecholamine related. In 14 (8.9%) cases, the likely
etiology of cardiomyopathy was chemotherapy-induced coronary vasospasm.
CONCLUSION: Our systematic review showed that over two-thirds of drug-induced TCM
cases were due to direct or indirect catecholamine stimulation. The lowest
effective dose and shortest duration of catecholamines should be utilized, and
alternative therapies should be considered if feasible.
PMID- 28490199
TI - Towards the Future Development of an Electrochemical Continuous Multimarker
Biosensor for Enhanced Glycemic Management.
PMID- 28490201
TI - A comparison of haemodynamics between subcranial-intracranial bypass and the
traditional extracranial-intracranial bypass.
AB - BACKGROUND: Ischemic cerebrovascular diseases are traditionally treated using an
extracranial-intracranial (EC-IC) bypass. The use of the internal maxillary
artery (IMA) in the subcranial-intracranial (SC-IC) bypass was recently described
as an alternative treatment. However, the haemodynamics of this new approach have
not been defined. METHODS: The haemodynamic parameters (flow volume [FV],
internal diameter [ID], time-averaged mean velocity [TAM], pulsatility index [PI]
and resistance index [RI]) of the IMA-radial artery graft (RAG)-middle cerebral
artery (MCA) (n = 12) bypass and superficial temporal artery (STA)-MCA bypass (n
= 18) were measured using intraoperative duplex ultrasonography and compared.
RESULTS: The FV was 81.36 +/- 30.41 (62.05-100.70) ml/min for the IMA-RAG-MCA
bypass. This was significantly higher than that of the STA-MCA bypass (27.25 +/-
9.32 (22.62-31.88) ml/min; P < .01). The ID and TAM in the IMA-RAG-MCA bypass
were higher than in the STA-MCA bypass (P < .01; P < .01). No significant
differences were observed in PI (P ~ .21) and RI (P ~ .08). The early patency
rate (one month after the operation) was 100% for the IMA-RAG-MCA bypass and 94%
for the STA-MCA bypass. CONCLUSIONS: The IMA-RAG-MCA bypass provides moderate to
high blood flow to the revascularized territory and blood flow was higher by this
method than the STA-MCA bypass.
PMID- 28490200
TI - Human Bocavirus Type-1 Capsid Facilitates the Transduction of Ferret Airways by
Adeno-Associated Virus Genomes.
AB - Human bocavirus type-1 (HBoV1) has a high tropism for the apical membrane of
human airway epithelia. The packaging of a recombinant adeno-associated virus 2
(rAAV2) genome into HBoV1 capsid produces a chimeric vector (rAAV2/HBoV1) that
also efficiently transduces human airway epithelia. As such, this vector is
attractive for use in gene therapies to treat lung diseases such as cystic
fibrosis. However, preclinical development of rAAV2/HBoV1 vectors has been
hindered by the fact that humans are the only known host for HBoV1 infection.
This study reports that rAAV2/HBoV1 vector is capable of efficiently transducing
the lungs of both newborn (3- to 7-day-old) and juvenile (29-day-old) ferrets,
predominantly in the distal airways. Analyses of in vivo, ex vivo, and in vitro
models of the ferret proximal airway demonstrate that infection of this
particular region is less effective than it is in humans. Studies of vector
binding and endocytosis in polarized ferret proximal airway epithelial cultures
revealed that a lack of effective vector endocytosis is the main cause of
inefficient transduction in vitro. While transgene expression declined
proportionally with growth of the ferrets following infection at 7 days of age,
reinfection of ferrets with rAAV2/HBoV1 at 29 days gave rise to approximately 5
fold higher levels of transduction than observed in naive infected 29-day-old
animals. The findings presented here lay the foundation for clinical development
of HBoV1 capsid-based vectors for lung gene therapy in cystic fibrosis using
ferret models.
PMID- 28490202
TI - Tumor necrosis factor inhibitors in psoriatic arthritis.
AB - INTRODUCTION: Psoriatic arthritis (PsA) is a chronic inflammatory disease that
can result in significant disability. With the emergence of tumor necrosis factor
inhibitors (TNFi), therapeutic outcomes in PsA have improved substantially. The
clinical efficacy and the inhibition of radiographic progression demonstrated by
TNFi have transformed the management of PsA. However, there is still an unmet
need for a subset of patients who do not respond adequately to TNFi. Areas
covered: This review provides an overview of the pharmacokinetics of TNFi, the
efficacy of TNFi in PsA, and the role of immunogenicity of TNFi in the treatment
of PsA. In addition, we address the use of TNFi in the setting of other
medications utilized in the treatment of PsA and the potential future role of
biosimilars. Expert commentary: Monoclonal antibodies exhibit complex and widely
variable pharmacokinetics. The study of factors that can affect the
pharmacokinetics, such as immunogenicity, is valuable to further define and
understand the use of TNFi in PsA, especially in the subset of patients who do
not respond adequately to these agents or lose effectiveness over time.
PMID- 28490203
TI - C-SAFE: A Computer-Delivered Sexual Health Promotion Program for Latinas.
AB - This article describes the development and evaluation of C-SAFE (Sexual Awareness
for Everyone), a computer-delivered sexual health promotion program for Latinas.
We first describe the process of adapting an evidence-based, group-level
intervention into an individually administered computer-delivered program. We
then present the methods and results of a randomized control trial with 321
Latinas in California and Florida to test C-SAFE's preliminary efficacy in
reducing sexual health risk. We found no statistically significant differences
between the two conditions at a six-month follow-up in terms of sexual behaviors
or attitudes toward sexually transmitted infections and condoms, although C-SAFE
women reported fewer days in the past month when their mental health was not good
(p = .02). C-SAFE condition women also reported more satisfaction than control
condition women in their assessment of information presentation (on a scale of 1
= poor and 5 = excellent; C-SAFE = 4.45 vs. control = 4.25, p = .053) and having
learned something new (C-SAFE = 95.1% vs. control = 79.3%, chi2 < 0.001), with
utility of content for Latinas approaching significance (C-SAFE = 4.50 vs.
control = 4.31, p = .058). In conclusion we discuss the importance of teachable
moments, matching of delivery modalities to implementation contexts, and possible
directions for evidence-based sexual health promotion programs given the current
sexual health landscape.
PMID- 28490204
TI - Exploring participatory behaviour of disability benefit claimants from an
insurance physician's perspective.
AB - PURPOSE: In the Dutch social security system, insurance physicians (IPs) assess
participatory behaviour as part of the overall disability claim assessment. This
study aims to explore the views and opinions of IPs regarding participatory
behaviour as well as factors related to inadequate participatory behaviour, and
to incorporate these factors in the International Classification of Functioning,
Disability and Health (ICF) biopsychosocial framework. METHOD: This qualitative
study collected data by means of open-ended questions in 10 meetings of local
peer review groups (PRGs) which included a total of 78 IPs of the Dutch Social
Security Institute. In addition, a concluding discussion meeting with 8 IPs was
organized. RESULTS: After qualitative data analyses, four major themes emerged:
(1) participation as an outcome, (2) efforts of disability benefit claimants in
the process of participatory behaviour, (3) beliefs of disability benefit
claimants concerning participation, and (4) recovery behaviour. Identified
factors of inadequate participatory behaviour covered all ICF domains, including
activities, environmental, and personal factors, next to factors related to
health condition and body functions or structures. Outcomes of the discussion
meeting indicated the impossibility of formulating general applicable criteria
for quantifying and qualifying participatory behaviour. CONCLUSIONS: Views of IPs
on disability benefit claimants' (in)adequate participatory behaviour reflect a
broad biopsychosocial perspective. IPs adopt a nuanced tailor-made approach
during assessment of individual disability benefit claimants' participatory
behaviour and related expected activities aimed at recovery of health and RTW.
Implications for Rehabilitation Within a biopsychosocial perspective, it is not
possible to formulate general criteria for the assessment of participatory
behaviour for each unique case. Individual disability benefit claimant
characteristics and circumstances are taken into account. To optimize the return
to-work (RTW) process, insurance physicians (IPs) assess participatory behaviour
according to the International Classification of Functioning, Disability and
Health, including medical, personal, and environmental factors. Some aspects
within the concept of participatory behaviour extend beyond the boundaries of the
domain where IPs operate because opinions in society on personal and societal
responsibility influence participatory behaviour.
PMID- 28490205
TI - Frequency and evaluation of the perceptions towards caesarean section among
pregnant women attending public hospitals in Pakistan and the implications.
AB - OBJECTIVES: There is increasing prevalence of caesarean sections (CS) worldwide;
however, there are concerns about their rates in some countries, including
potential fears among mothers. Consequently, we aimed to determine the frequency
of CS, and explore patient's perception towards CS attending public hospitals in
Pakistan, to provide future guidance. METHODS: A two-phased study design
(retrospective and cross sectional) was adopted. A retrospective study was
conducted to assess the frequency of CS over one year among four public
hospitals. A cross sectional study was subsequently conducted to determine
patients' perception towards CS attending the four tertiary care public hospitals
in Quetta city, Pakistan, which is where most births take place. RESULTS: Overall
prevalence of CS was 13.1% across the four hospitals. 728 patients were
approached and 717 responded to the survey. Although 78.8% perceived CS as
dangerous, influenced by education (p = 0.004), locality (p = 0.001) and
employment status (p = 0.001), 74.5% of patients were in agreement that this is
the best approach to save mother's and baby's lives if needed. 62% of respondents
reported they would like to avoid CS if they could due to post-operative pain,
and 58.9% preferred a normal delivery. There was also a significant association
with education (p = 0.001) and locality (p = 0.001) where respondents considered
normal vaginal delivery as painful. CONCLUSION: The overall frequency of CS
approximates to WHO recommendations, although there is appreciable variation
among the four hospitals. When it comes to perception towards CS, women had
limited information. There is a need to provide mothers with education during the
antenatal period, especially those with limited education, to accept CS where
needed.
PMID- 28490206
TI - Pharmacokinetics, pharmacodynamics and pharmacogenetics associated with
nonsteroidal anti-inflammatory drugs and opioids in pediatric cancer patients.
AB - INTRODUCTION: Advancing appropriate and adequate analgesic pharmacotherapy in
pediatric patients with cancer is an area of clinical need. Few studies have been
performed to evaluate the selection of an analgesic and appropriate dosing
corresponding to analgesic effect among pediatric cancer patients. This review
describes information related to pharmacokinetic, pharmacodynamic, and
pharmacogenomic (when applicable) considerations for analgesics that are commonly
used to manage pain experienced by pediatric patients with cancer. Areas covered:
Analgesics commonly used to treat pediatric patients with malignancy patterned
after the World Health Organization's 'analgesic ladder' for cancer pain
management. Expert opinion: Addressing pain management safely and effectively in
pediatric patients with cancer will require advances in both drug development, to
increase the armament of analgesics available for children, and our pharmacologic
understanding of those analgesics in current use. However, performing the
necessary types of studies to develop new analgesics, or gain knowledge of
existing therapy, within a population that is relatively small, diverse, and who
experience pain originating from a variety of sources, is a tremendous challenge.
PMID- 28490207
TI - microRNA-124: a putative therapeutic target and biomarker for major depression.
PMID- 28490208
TI - Plasma kisspeptin levels in lactational amenorrhea.
AB - The kisspeptin is a neuropeptide to play physiological roles in regulating
gonadotropin-releasing hormone secretion in the hypothalamus. In human plasma,
the kisspeptin concentration is measured, but gonadotropin-releasing hormone is
not. This study aims to understand the physiological roles of the circulating
kisspeptin in lactational amenorrhea in humans because prolactin reduces the
kisspeptin expression and luteinizing hormone secretion resulting in anovulations
in rodent brains. Plasma kisspeptin levels were measured in 11 subjects in
lactational amenorrhea and in four cases with pathological amenorrhea by
different etiologies for comparison using the enzyme immunoassay specific for
human kisspeptin. The plasma kisspeptin levels in the 11 women with lactational
amenorrhea were 15.2 +/- 2.5 fmol/mL (mean +/- SD) which were not significantly
different as compared with 16.5 +/- 4.8 fmol/mL (mean +/- SD) in four age-matched
women with menstrual cycles as we reported previously. In the four cases with
pathological amenorrhea, their plasma kisspeptin levels were from 5.8 to 13.7
fmol/mL. This study demonstrated that the plasma kisspeptin levels were not
totally reduced in lactational or pathological amenorrhea. These results suggest
the physiological roles of the circulating kisspeptin are different from the role
in the brain.
PMID- 28490209
TI - Retrospective analysis in 46 women with vulvovaginal atrophy treated with
ospemifene for 12 weeks: improvement in overactive bladder symptoms.
AB - AIMS: The aim of this study was to assess the effectiveness and safety of
ospemifene in the improvement of overactive bladder (OAB) symptoms in
postmenopausal women affected by vulvovaginal atrophy (VVA). METHODS: Forty-six
postmenopausal patients affected by VVA with OAB syndrome were enrolled for the
study. All patients received Ospemifene 60 mg for 12 weeks. Clinical examination,
3-day voiding diary, urodynamic testing, ultrasound measurement of endometrial
and bladder wall thickness (BWT) and the Vaginal Health Index (VHI) were
performed at baseline and 12 weeks. Patients completed the OAB-Q SF and UDI-6.
RESULTS: After 12-weeks, the number of patients with detrusor overactivity
decreased from 39% to 13% (p = 0.04). The reduction in the mean number in 24 h of
voids (9.57 +/- 2.12 vs. 6.63 +/- 1.22, p < 0.0001), urgent micturition
episodes/24 h (5.63 +/- 1.46 vs. 1.44 +/- 1.31, p < 0.0001), nocturia episodes
(3.17 +/- 0.85 vs. 1.11 +/- 1.18, p < 0.0001), urinary incontinence episodes/24 h
(0.85 +/- 0.96 vs. 0.33 +/- 0.64, p = 0.003) was observed. The UDI-6, OAB-Q
symptoms, OAB-Q (HRQL) scores were 8.95 +/- 0.91 vs. 5.56 +/- 1.40, 62.60 +/-
14.70 vs. 20.08 +/- 10.83 and 18.71 +/- 7.41 vs. 79.45 +/- 14.47 (p < 0.001)
before and after 12 weeks. CONCLUSION: Ospemifene is an effective potential
therapy for postmenopausal women with VVA improving OAB symptoms and quality of
life.
PMID- 28490210
TI - ADHD Symptoms and Quality of Life Across a 12-Month Period in Children With ADHD:
A Longitudinal Study.
AB - OBJECTIVE: To describe the relationship between ADHD symptom severity and quality
of life (QoL) across three time points over a 12-month period and investigate
whether sleep modifies this relationship. METHOD: Children aged 5 to 13 years
with ADHD were recruited from 21 pediatric practices across Victoria, Australia (
N = 392). Child QoL (parent-report) and ADHD symptoms (both parent- and teacher
report) were assessed at three time points (0, 6, and 12 months), and sleep was
assessed at baseline (parent-report). Data were analyzed using Pearson's
correlations and autoregressive cross-lagged panel models. RESULTS: Parent
reported ADHD symptoms predicted poorer QoL at each subsequent time point ( r =
.10 to -.13), and a small bidirectional relationship was observed between teacher
reported ADHD symptoms and QoL from 6 to 12 months. Sleep moderated the
relationship between ADHD symptoms and QoL. CONCLUSION: Clinicians need to look
beyond core ADHD symptoms to other factors that may be influencing QoL in
children with ADHD.
PMID- 28490212
TI - Effects of ADHD on Writing Composition Product and Process in School-Age
Students.
AB - OBJECTIVE: This study examined the relationship between ADHD and writing
performance. METHOD: Students in Grades 3 to 7, 84 with ADHD and 135 age- and
gender-matched controls completed a writing task (including process logs), and
measures of working memory and attention. RESULTS: Students with ADHD wrote texts
of similar length but with poorer structure, coherence, and ideation. In all,
6.7% of the variance in writing quality was explained by whether or not the
student had an ADHD diagnosis, after control for IQ and age-within-year, with
ADHD students producing text that was less coherent, well structured, and
ideationally rich, and spending less time thinking about and reviewing their
text. Half of the effect on text quality could be attributed to working memory
and sustained attention effects. CONCLUSION: ADHD has some effect on writing
performance, which can, in part, be explained by working memory and attentional
deficits.
PMID- 28490213
TI - Are fluorescence-based chlorophyll quantification methods suitable for algae
toxicity assessment of carbon nanomaterials?
AB - Using a multiwalled carbon nanotube (MWCNT) and graphene oxide (GO) as
representative test materials, we evaluated the applicability of in vivo and in
vitro chlorophyll-a (Chl-a) fluorescence quantification methods, which are used
in standard algae ecotoxicity tests such as OECD 201 and ISO 8692. In vivo
quantification of Chl-a from Raphidocelis subcapitata indicated a significant
reduction in Chl-a fluorescence in the presence of MWCNTs due to shading, but a
significant autofluorescence from GO caused an overestimation of Chl-a
concentration. In vitro Chl-a quantification methods employing a modified acetone
and an ethanol extraction protocol reduced the influence of shading and
autofluorescence, but both resulted in a significant loss of fluorescence signal
in the presence of 100 mgL-1 MWCNTs (99-100%) and GO (21-52%). Chl-a reduction
was dose dependent for both tested carbon-based MNMs (CNMs), but effects were
more pronounced for MWCNT, which caused a significant fluorescence reduction (16
+/- 0.3%) already at 1 mgL-1. Further study of the CNM-algae-Chl-a interaction
processes revealed that CNM can not only interact with live algae, but also
efficiently adsorb extracted Chl-a. Our results showed that within 10 min, 95
100% of Chl-a extracted from two algae concentrations were adsorbed to MWCNT,
while 35-60% of Chl-a was adsorbed to the GO. This study shows that Chl-a
quantification by fluorescence determination is not a suitable method for
ecotoxicity testing of CNM. However, a quick screening test for individual MNMs
is recommended to determine whether Chl-a adsorption is a significant process
prior to selection of a quantification method.
PMID- 28490214
TI - Emerging amyloid and tau targeting treatments for Alzheimer's disease.
AB - INTRODUCTION: With an ageing global population, the number of people with
dementia, and its main cause Alzheimer's disease (AD), is growing. current
licensed treatments available for ad are only alleviate the symptoms of the
disease, and are effective only in some people with ad for a limited time. there
are currently no therapies that target the disease process. Areas covered: This
review summarizes the available treatments for AD and the emerging therapies in
the clinical trials pipeline. There are ongoing trials at various stages of
development, targeting different mechanisms and pathways implicated in the
disease. This review focuses on amyloid and tau targeting drug candidates. Expert
commentary: Despite research efforts targeted at understanding AD, the underlying
mechanisms and optimal treatment targets have not been fully elucidated. There is
a significant need for further research targeting the disease at an earlier stage
and progress in biomarker and imaging technology are improving the outlook. It is
critical to continue research into identifying the underlying pathology and
disease process in Alzheimer's disease to enable development of effective
targeted treatments.
PMID- 28490215
TI - The safety of daratumumab for the treatment of multiple myeloma.
AB - INTRODUCTION: The overall survival of patients with multiple myeloma (MM) has
changed dramatically in the last decade. MM remains an incurable plasma cell
disorder but immunotherapy with monoclonal antibodies (MoAbs) has emerged as a
promising treatment. Areas covered: Fully published, clinical trials including
patients with relapsed or refractory MM were reviewed. Safety data of daratumumab
(DARA) single-agent or in combination regimens have been addressed. Additionally,
infusion-related reactions, data on special populations, and DARA-interference
with laboratory testing, including assessment of MM response in patients have
also been addressed. Expert opinion: Daratumumab both as single agent and in
combination regimens has shown a favorable safety profile without significant
increase in toxicities. Extensive clinical development of DARA is currently
ongoing and given the efficacy that has been seen with this drug in clinical
trials, DARA is likely to change the landscape of myeloma treatment.
PMID- 28490216
TI - Prevalence and Psychosocial Correlates of ADHD Symptoms in Young Adulthood: A
French Population-Based Study.
AB - OBJECTIVE: The scientific literature suggests that ADHD in adulthood is
associated with a considerable psychosocial burden. However, most knowledge in
this area relies on studies conducted in the United States or in North European
nations, thereby limiting generalization to other countries. METHOD: We assessed
the psychosocial correlates of ADHD symptoms in a French community-based sample.
Data came from 1,214 community-based young adults (18-35 years) and their parents
(Trajectoires Epidemiologiques en Population and GAZEL studies). ADHD symptoms
and socioeconomic and psychosocial correlates were assessed in a telephone
interview. Logistic regression analyses were conducted to assess associations.
RESULTS: A total of 7.1% of the sample presented high levels of ADHD symptoms.
Parental history of anxiety, dissatisfaction with love life, and consumption of
tobacco were associated with the highest odds ratios. CONCLUSION: This study
confirms the high functional impairment associated with adult ADHD symptoms in a
French community sample. It extends the existing literature to family risk
correlates and individual well-being correlates.
PMID- 28490211
TI - Adeno-Associated Virus Vectors and Stem Cells: Friends or Foes?
AB - The infusion of healthy stem cells into a patient-termed "stem-cell therapy"-has
shown great promise for the treatment of genetic and non-genetic diseases,
including mucopolysaccharidosis type 1, Parkinson's disease, multiple sclerosis,
numerous immunodeficiency disorders, and aplastic anemia. Stem cells for cell
therapy can be collected from the patient (autologous) or collected from another
"healthy" individual (allogeneic). The use of allogenic stem cells is accompanied
with the potentially fatal risk that the transplanted donor T cells will reject
the patient's cells-a process termed "graft-versus-host disease." Therefore, the
use of autologous stem cells is preferred, at least from the immunological
perspective. However, an obvious drawback is that inherently as "self," they
contain the disease mutation. As such, autologous cells for use in cell therapies
often require genetic "correction" (i.e., gene addition or editing) prior to cell
infusion and therefore the requirement for some form of nucleic acid delivery,
which sets the stage for the AAV controversy discussed herein. Despite being the
most clinically applied gene delivery context to date, unlike other more
concerning integrating and non-integrating vectors such as retroviruses and
adenovirus, those based on adeno-associated virus (AAV) have not been employed in
the clinic. Furthermore, published data regarding AAV vector transduction of stem
cells are inconsistent in regards to vector transduction efficiency, while the
pendulum swings far in the other direction with demonstrations of AAV vector
induced toxicity in undifferentiated cells. The variation present in the
literature examining the transduction efficiency of AAV vectors in stem cells may
be due to numerous factors, including inconsistencies in stem-cell collection,
cell culture, vector preparation, and/or transduction conditions. This review
summarizes the controversy surrounding AAV vector transduction of stem cells,
hopefully setting the stage for future elucidation and eventual therapeutic
applications.
PMID- 28490217
TI - Antimicrobial proteins in the response to graphene oxide in Caenorhabditis
elegans.
AB - Upon exposure to environmental engineered nanomaterials (ENMs), animals will
activate certain response signals to protect themselves from the toxic effects.
However, the underlying molecular mechanisms for this response are still largely
unclear. Using in vivo assay system of Caenorhabditis elegans, we here found that
antimicrobial proteins of LYS-1, LYS-8, SPP-1, DOD-6, and F55G11.4 were activated
by graphene oxide (GO) exposure. These antimicrobial proteins functioned as
molecular targets of transcriptional factor DAF-16 in insulin signaling pathway,
and acted in intestine to regulate the response to GO. Among these antimicrobial
proteins, DOD-6, F55G11.4, and SPP-1 participated in the formation of signaling
cascade of DAF-16-DOD-6-SOD-3-F55G11.4/SPP-1 in response to GO exposure by
activating the antioxidation system. Different from this, LYS-1 and LYS-8, two
lysozymes, mediated TUB-2 signaling and DAF-8-DAF-5 signaling cascade,
respectively, to regulate the response to GO exposure. During the regulation of
response to GO exposure, LYS-1 and LYS-8 acted synergistically, which could be
largely explained by the observed synergistic interaction between TUB-2 and DAF
8. Therefore, our results demonstrate the crucial protection role of
antimicrobial proteins for animals in response to environmental ENMs' exposure.
The elucidated different signaling cascades mediated by antimicrobial proteins
provide important molecular targets for future toxicity assessment and chemical
modification of GO.
PMID- 28490218
TI - Evaluation of clinical prognostic factors for interstitial pneumonia in anti-MDA5
antibody-positive dermatomyositis patients.
AB - OBJECTIVES: We retrospectively investigated clinical prognostic factors for
interstitial pneumonia (IP) in anti-melanoma differentiation-associated gene 5
(MDA5) antibody (Ab)-positive dermatomyositis (DM) patients. METHODS: Subjects
comprised 18 patients with anti-MDA5 Ab-positive DM-IP (9 survivors; 9 deaths).
RESULTS: Initial serum albumin levels, ferritin levels, and ground-glass opacity
(GGO) scores in the right middle lobes were significantly higher in the death
group than in the survivor group (p = .033, .013, and .005, respectively).
Initial alveolar-arterial oxygen gradient (P[A-a]O2) was also higher in the death
group than in the survivor group (p = .064). Initial serum ferritin, P[A-a]O2,
and right middle lobe GGO score were found to significantly relate to death.
Survival rates after 24 weeks were significantly lower among patients with an
initial ferritin level of >=450 ng/mL (25%), P[A-a]O2 of >=30 mmHg (31%), and a
right middle lobe GGO score of >=2 (11%) than each of the others (p = .006, .020,
and .002, respectively). CONCLUSIONS: An initial serum ferritin level of >=450
ng/mL, P[A-a]O2 of >=30 mmHg, and right middle lobe GGO score of >=2 (GGO >=5% of
the lobe) were identified as poor prognostic factors for anti-MDA5 Ab-positive DM
IP patients.
PMID- 28490220
TI - Solithromycin (CEM-101): A New Fluoroketolide Antibiotic and Its Role in the
Treatment of Gonorrhea.
AB - Solithromycin is a macrolide antibiotic that has undergone review for the
treatment of community-acquired bacterial pneumonia. Solithromycin is also being
investigated and has shown promise for the treatment of gonorrhea. With
increasing antibiotic resistance, the development of novel antibiotics to combat
infections is essential. The unique ribosome-binding stability of solithromycin
and mild side effect profile make this a promising new antibiotic. This article
will provide an overview on the mechanism of action, clinical efficacy, and
safety of this drug for the treatment of gonorrhea. Relevant data were identified
through a comprehensive literature search using multiple databases using the
keywords solithromycin, CEM-101, and gonorrhea.
PMID- 28490221
TI - Natural Health Products and Community Pharmacy-Remove the Mysticism Not the
Product.
AB - The allure of natural products has captivated humans for centuries. Although they
can be compatible with evidence-based care, attitudes surrounding natural
products can seem almost mystical and may even be accompanied by contempt toward
Western medicine. Considering the high volumes of natural products sold in
community pharmacies, pharmacists can inject balanced information to minimize the
mysticism and help patients make informed decisions. The aim of this article is
to argue for standardized guidelines pertaining to the management of natural
products in community pharmacy practice.
PMID- 28490222
TI - Inattention and Hyperactivity-Impulsivity: Their Detrimental Effect on Romantic
Relationship Maintenance.
AB - OBJECTIVE: The aim of this study is to understand how ADHD symptoms correlate
with romantic relationship maintenance and test theoretical pathways by which
symptoms of ADHD lead to relationship difficulties. METHOD: This study involved
two phases of data collection, which were identical except for the population.
Phase 1 ( n = 172) was a nonclinical sample of romantically involved young
adults. Phase 2 ( n = 39) was a clinical sample of romantically involved young
adults with ADHD. Participants in both phases reported on their levels of
inattention and hyperactivity-impulsivity, their relationship maintenance
activities, and their relationship quality. RESULTS: ADHD symptoms were
associated with greater relationship difficulties. In both samples, inattentive
symptoms were associated with greater interest in relational alternatives and
less constructive responses to partner's bad behaviors, whereas hyperactive
impulsive symptoms were associated with negative responses to bad behavior.
CONCLUSION: The results of this study have implications for developing cognitive
behavioral therapy interventions targeting relationship difficulties in young
adults with ADHD.
PMID- 28490219
TI - Recruitment of macrophages from the spleen contributes to myocardial fibrosis and
hypertension induced by angiotensin II.
AB - INTRODUCTION: The purpose of this study was to determine whether macrophages
migrated from the spleen are associated with angiotensin II-induced cardiac
fibrosis and hypertension. METHODS: Sprague-Dawley rats were subjected to
angiotensin II infusion in vehicle (500 ng/kg/min) for up to four weeks. In
splenectomy, the spleen was removed before angiotensin II infusion. In the
angiotensin II AT1 receptor blockade, telmisartan was administered by gastric
gavage (10 mg/kg/day) during angiotensin II infusion. The heart and aorta were
isolated for Western blot analysis and immunohistochemistry. RESULTS: Angiotensin
II infusion caused a significant reduction in the number of monocytes in the
spleen through the AT1 receptor-activated monocyte chemoattractant protein-1.
Comparison of angiotensin II infusion, splenectomy and telmisartan comparatively
reduced the recruitment of macrophages into the heart. Associated with this
change, transforming growth factor beta1 expression and myofibroblast
proliferation were inhibited, and Smad2/3 and collagen I/III were downregulated.
Furthermore, interstitial/perivascular fibrosis was attenuated. These
modifications occurred in coincidence with reduced blood pressure. At week 4,
invasion of macrophages and myofibroblasts in the thoracic aorta was attenuated
and expression of endothelial nitric oxide synthase was upregulated, along with a
reduction in aortic fibrosis. CONCLUSIONS: These results suggest that macrophages
when recruited into the heart and aorta from the spleen potentially contribute to
angiotensin II-induced cardiac fibrosis and hypertension.
PMID- 28490223
TI - Molecular remodeling of the renin-angiotensin system after kidney
transplantation.
AB - OBJECTIVE: We aimed at assessing the molecular adaptation of the renin
angiotensin system (RAS) after successful kidney transplantation (KTX). MATERIALS
AND METHODS: In this prospective, exploratory study we analyzed 12 hemodialysis
(HD) patients, who received a KTX and had excellent graft function six to 12
months thereafter. The concentrations of plasma Angiotensin (Ang) peptides (Ang
I, Ang II, Ang-(1-7), Ang-(1-5), Ang-(2-8), Ang-(3-8)) were simultaneously
quantified with a novel mass spectrometry-based method. Further, renin and
aldosterone concentrations were determined by standard immunoassays. RESULTS: Ang
values showed a strong inter-individual variability among HD patients. Yet,
despite a continued broad dispersion of Ang values after KTX, a substantial
improvement of the renin/Ang II correlation was observed in patients without RAS
blockade or on angiotensin receptor blocker (HD: renin/Ang II R2 = 0.660, KTX:
renin/Ang II R2 = 0.918). Ang-(1-7) representing the alternative RAS axis was
only marginally detectable both on HD and after KTX. CONCLUSIONS: Following KTX,
renin-dependent Ang II formation adapts in non-ACE inhibitor-treated patients.
Thus, a largely normal RAS regulation is reconstituted after successful KTX.
However, individual Ang concentration variations and a lack of potentially
beneficial alternative peptides after KTX call for individualized treatment. The
long-term post-transplant RAS regulation remains to be determined.
PMID- 28490224
TI - Prevalence of Abnormal Magnetic Resonance Imaging Findings in Children with
Persistent Symptoms after Pediatric Sports-Related Concussion.
AB - A subset of patients experience persistent symptoms after pediatric concussion,
and magnetic resonance imaging (MRI) is commonly used to evaluate for pathology.
The utility of this practice is unclear. We conducted a retrospective cohort
study to describe the MRI findings in children with concussion. A registry of all
patients seen at our institution from January 2010 through March 2016 with
pediatric sports-related concussion was cross-referenced with a database of
radiographical studies. Radiology reports were reviewed for abnormal findings.
Patients with abnormal computed tomographies or MRI scans ordered for reasons
other than concussion were excluded. Among 3338 children identified with
concussion, 427 underwent MRI. Only 2 (0.5%) had findings compatible with
traumatic injury, consisting in both of microhemorrhage. Sixty-one patients
(14.3%) had abnormal findings unrelated to trauma, including 24 nonspecific T2
changes, 15 pineal cysts, eight Chiari I malformations, and five arachnoid cysts.
One child underwent craniotomy for a cerebellar hemangioblastoma after presenting
with ataxia; another had cortical dysplasia resected after seizure. The 2
patients with microhemorrhage each had three previous concussions, significantly
more than patients whose scans were normal (median, 1) or abnormal without injury
(median, 1.5; p = 0.048). MRI rarely revealed intracranial injuries in children
post-concussion, and the clinical relevance of these uncommon findings remains
unclear. Abnormalities unrelated to trauma are usually benign. However, MRI
should be thoughtfully considered in children who present with concerning or
atypical symptoms.
PMID- 28490225
TI - Is a short arm cast appropriate for stable distal radius fractures in patients
older than 55 years? A randomized prospective multicentre study.
AB - : We conducted a prospective randomized, multicentre study to compare short arm
and long arm plaster casts for the treatment of stable distal radius fracture in
patients older than 55 years. We randomly assigned patients over the age of 55
years who had stable distal radius fracture to either a short arm or long arm
plaster cast at the first review 1 week after their injury. Radiographic and
clinical follow-up was conducted at 1, 3, 5, 12 and 24 weeks following their
injury. Also, degree of disability caused by each cast immobilization was
evaluated at the patient's visit to remove the cast. There were no significant
differences in radiological parameters between the groups except for volar tilt.
Despite these differences in volar tilt, neither functional status as measured by
the Disabilities of the Arm, Shoulder and Hand, nor visual analogue scale was
significantly different between the groups. However, the mean score of disability
caused by plaster cast immobilization and the incidence rate of shoulder pain
were significantly higher in patients who had a long plaster cast. Our findings
suggest that a short arm cast is as effective as a long arm cast for stable
distal radius fractures in the elderly. Furthermore, it is more comfortable and
introduces less restriction on daily activities. LEVEL OF EVIDENCE: II.
PMID- 28490227
TI - Utilization of Continuous "Spinners" to Communicate Risk.
AB - BACKGROUND: As patients become more involved in their medical care, they must
consider the specific probabilities of both positive and negative outcomes
associated with different treatments. Patients who are low in numeracy may be at
a disadvantage when making these decisions. This study examined the use of a
"spinner" to present probabilistic information compared to a numerical format and
icon array. DESIGN: Subjects ( n = 151) were asked to imagine they suffered from
chronic back pain. Two equally effective medications, each with a different
incidence of rare and common side effects, were described. Subjects were
randomized to 1 of 3 risk presentation formats: numeric only, numeric with icon
arrays, or numeric with spinners, and answered questions regarding their risk
knowledge, medication preference, and how much they liked the presentation
format. RESULTS: Compared with the numeric only format, both the spinner and icon
array increased risk knowledge and were rated more likeable by subjects. Subjects
viewing the spinner format were also more likely to prefer the pill with the
lowest side-effect burden. LIMITATIONS: The relatively small size, convenience
sample, and hypothetical scenario were limitations of this study. CONCLUSIONS:
The use of continuous spinners presents a new approach for communicating risk to
patients that may aid in their decision making.
PMID- 28490226
TI - Intensity of hydration changes the role of renin-angiotensin-aldosterone system
blockers in contrast-induced nephropathy risk after coronary catheterisation in
patients with chronic kidney disease.
AB - OBJECTIVE: This study evaluated the potential effect of hydration intensity on
the role of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin
receptor blockers (ARBs) on contrast-induced nephropathy in patients with renal
insufficiency. METHODS: All eligible patients were included and stratified
according to hydration intensity defined as saline hydration volume to body
weight tertiles: <10.21 mL/kg, 10.21 to <17.86 mL/kg, and ?17.86 mL/kg. RESULTS:
In total, 84 (6.7%) of 1254 patients developed contrast-induced nephropathy: 6.2%
in the ACEI/ARB group versus 10.8% in the non-ACEI/ARB group ( P=0.029), with an
adjusted odds ratio (OR) of 0.89 (95% confidence interval (CI) 0.46-1.73,
P=0.735). The incidence of contrast-induced nephropathy was lower in the ACEI/ARB
group than in the non-ACEI/ARB group in the second tertile ( P=0.031), while not
significantly different in the first ( P=0.701) and third ( P=0.254) tertiles.
ACEIs/ARBs were independently associated with a lower contrast-induced
nephropathy risk (OR 0.26, 95% CI 0.09-0.74, P=0.012) and long-term all-cause
death (hazard ratio 0.461, 95% CI 0.282-0.755, P=0.002) only in the second
hydration volume to body weight tertile. CONCLUSION: The effects of ACEIs/ARBs on
contrast-induced nephropathy risk vary according to saline hydration intensity in
chronic kidney disease patients, and may further reduce contrast-induced
nephropathy risk in patients administered moderate saline hydration.
PMID- 28490228
TI - Concussion Mechanisms and Activities in Youth, High School, and College Football.
AB - Our purpose was to determine concussion mechanism and activity differences among
three cohorts of football players: youth, high school, and college. Participants
in this prospective cohort study were youth (ages 5-14 years, 118 teams, 310 team
seasons), high school (96 teams, 184 team-seasons), and college (34 teams, 71
team-seasons) football players. Athletic trainers collected athlete-exposure (AE)
and concussion data during the 2012-2014 seasons. Injury mechanism referred to
the object that made contact with the concussed player, resulting in the
concussion. Injury activity referred to the type of football-specific activity
that the player was involved in when the concussion was sustained. Injury
proportion ratios (IPR) compared distributions of concussion mechanisms and
activities among age levels. A total of 1429 concussions were reported over
1,981,284 AE across all levels (Rate: 0.72/1000AE). Overall, most concussions
were caused by player contact (84.7%). During games, a greater proportion of
youth football concussions (14.7%) were caused by surface contact than high
school (7.3%, IPR = 2.02; 95% confidence interval [CI]: 1.10-3.72) and college
(7.1%, IPR = 2.07, 95% CI: 1.02-4.23) football. Compared with college football
concussions (90.2%), a smaller proportion of youth (80.0%, IPR = 0.89, 95% CI:
0.79-0.99) and high school (83.2%, IPR = 0.92, 95% CI: 0.86-0.99) football
concussions were caused by player contact. A greater proportion of game youth
football concussions (42.1%) occurred while an individual was being tackled than
occurred in high school (23.2%, IPR = 1.81, 95% CI: 1.34-2.45) and college
(23.0%, IPR = 1.83, 95% CI: 1.29-2.62) football. Findings were similar during
practices. Compared with college football game concussions (15.8%), a smaller
proportion of youth (6.3%, IPR = 0.40, 95% CI: 0.17-0.93) and high school (9.5%,
IPR = 0.60, 95% CI: 0.38-0.95) football game concussions occurred while an
individual was being blocked. Concussion mechanism and activity differences
should be considered when developing concussion prevention and sport-safety
methods specific to different age levels, in order to maximize effectiveness.
PMID- 28490229
TI - Changes in blood pressure among patients in the Ontario Telehomecare programme:
An observational longitudinal cohort study.
AB - Background The objective of this study was to investigate the changes in blood
pressure among patients enrolled in the Telehomecare programme in Ontario,
Canada. Methods This observational study utilised a prospective longitudinal
cohort design, including patients with heart failure and chronic obstructive
pulmonary disease enrolled in the Ontario Telehomecare programme from July 2012
to July 2015. The outcome of interest was change in mean (biweekly) systolic and
diastolic blood pressure levels over a six-month period. Patient data were
extracted from the Ontario Telemedicine Network database, and analysed using
generalised linear mixed model procedures. Results Overall, we analysed data for
3513 patients. Patients were on average 74.1 +/- 11.4 years of age; almost half
were men, 62% had heart failure, 55% chronic obstructive pulmonary disease and
29% diabetes. At baseline, the mean systolic and diastolic blood pressure levels
were 130.4 +/- 19.1 mmHg and 72.2 +/- 12.5 mmHg for the total sample. At six
months, the adjusted reduction in systolic and diastolic blood pressure values
were 4.0 mmHg (95% confidence interval: -4.5 to -3.5) and 2.7 mmHg (95%
confidence interval: -3.1 to -2.4), respectively. In a subgroup of 1220 patients
with uncontrolled blood pressure at baseline (systolic/diastolic blood pressure
of 150.7 +/- 10.2 mmHg/80.2 +/- 13.5 mmHg) the adjusted reduction in systolic
blood pressure was 12.5 mmHg (95% confidence interval: -13.4 to -11.6) and in
diastolic blood pressure was 7.1 mmHg (95% confidence interval: -7.8 to -6.5)
over the six-month period. Conclusions Blood pressure levels were significantly
reduced in patients enrolled in the Telehomecare programme, with changes being
more pronounced in patients with uncontrolled blood pressure. The sustainability
of decreased blood pressure on other clinical outcomes needs further evaluation.
PMID- 28490230
TI - Acceptability of In Utero Hematopoietic Cell Transplantation for Sickle Cell
Disease.
AB - BACKGROUND: In utero hematopoietic cell transplantation (IUHCT) has curative
potential for sickle cell disease (SCD) but carries a risk of fetal demise.
METHODS: We assessed the conditions under which parents of children with SCD and
young adults with SCD would consider IUHCT in a future pregnancy, given a 5%
fixed risk of fetal demise. Participants were randomized to consider a
hypothetical cure rate (20%, 40%, or 70%). Subsequently, cure rate was either
increased or decreased depending on the previous answer to reveal the lowest
acceptable rate. Participants also completed the Pediatric Research Participation
Questionnaire (PRPQ) and an omission scale. RESULTS: Overall, 74 of 79 (94%)
participants were willing to consider IUHCT, and 52 (66%) participants accepted
IUHCT at a cure rate of 40%, the estimated rate of therapeutic mixed chimerism.
Participants with higher scores on the PRPQ perceived benefits scale were more
likely to participate at lower cure rates (OR 1.08, p=0.007) and participants
with a greater degree of omission bias were less likely to participate at lower
cure rates (OR 0.83, p=0.04). Demographics and SCD severity were not
significantly associated with acceptability of IUHCT. CONCLUSION: This study
suggests that the majority of parents >and young adults would consider IUHCT
under expected therapeutic conditions.
PMID- 28490231
TI - Energy and Protein Delivery in Overweight and Obese Children in the Pediatric
Intensive Care Unit.
AB - BACKGROUND: Early and optimal energy and protein delivery have been associated
with improved clinical outcomes in the pediatric intensive care unit (PICU).
Overweight and obese children in the PICU may be at risk for suboptimal
macronutrient delivery; we aimed to describe macronutrient delivery in this
cohort. METHODS: We performed a retrospective study of PICU patients ages 2-21
years, with body mass index (BMI) >=85th percentile and >48 hours stay. Nutrition
variables were extracted regarding nutrition screening and assessment, energy and
protein prescription, and delivery. RESULTS: Data from 83 patient encounters for
52 eligible patients (52% male; median age 9.6 [5-15] years) were included. The
study cohort had a longer median PICU length of stay (8 vs 5 days, P < .0001) and
increased mortality rate (6/83 vs 182/5572, P = .045) than concurrent PICU
patient encounters. Detailed nutrition assessment was documented for 60% (50/83)
of patient encounters. Energy expenditure was estimated primarily by predictive
equations. Stress factor >1.0 was applied in 44% (22/50). Median energy delivered
as a percentage of estimated requirements by the Schofield equation was 34.6% on
day 3. Median protein delivered as a percentage of recommended intake was 22.1%
on day 3. CONCLUSIONS: The study cohort had suboptimal nutrition assessments and
macronutrient delivery during their PICU course. Mortality and duration of PICU
stay were greater when compared with the general PICU population. Nutrition
assessment, indirect calorimetry-guided energy prescriptions, and optimizing the
delivery of energy and protein must be emphasized in this cohort. The impact of
these practices on clinical outcomes must be investigated.
PMID- 28490232
TI - The Candy-Plug Technique: Technical Aspects and Early Results of a New
Endovascular Method for False Lumen Occlusion in Chronic Aortic Dissection.
AB - PURPOSE: To describe the technical aspects and early results of the Candy-Plug
technique for endovascular false lumen occlusion in chronic aortic dissection.
METHODS: A retrospective single-center study analyzing 18 consecutive patients
(mean age 63 years, range 44-76; 16 men) with thoracic false lumen aneurysm in
chronic aortic dissection. All patients underwent thoracic endovascular aortic
repair with false lumen occlusion using the Candy-Plug technique. Primary
endpoints consisted of technical success (successful deployment) and clinical
success (no false lumen backflow). Secondary endpoints included 30-day mortality
and morbidity as well as aortic remodeling during follow-up. RESULTS: Technical
success was 100%. Additional intraprocedural false lumen embolization at the
Candy-Plug level was needed in 1 patient due to persisting false lumen backflow
on the final angiogram (clinical success 94%). There were no intraprocedural
complications. In the perioperative period, there were 3 minor complications:
transient mild spinal cord ischemia, cervical hematoma after carotid-subclavian
bypass, and a common femoral artery pseudoaneurysm. No deaths or reinterventions
occurred. Complete distal false lumen occlusion was present on postoperative
computed tomography in 15 patients, while 3 had minor contrast enhancement in the
distal false lumen. Over a mean 9-month follow-up (range 0-26), 1 patient died
due to rupture. Follow-up >6 months was available in 10 patients (mean 14.7
months, range 7-26): 7 patients showed aortic remodeling, while aneurysm size was
stable in 3 patients. CONCLUSION: The Candy-Plug technique is a feasible
endovascular method to achieve false lumen occlusion and aortic remodeling in
chronic aortic dissection. It is associated with low morbidity and mortality due
to its minimal invasiveness.
PMID- 28490233
TI - Update on Finger-Application-Type Noninvasive Continuous Hemodynamic Monitors
(CNAP and ccNexfin): Physical Principles, Validation, and Clinical Use.
AB - The CNAP HD Monitor (CNSystems, Graz, Austria) and the ccNexfin (The ClearSight
System: Edwards Lifesciences Corporation, Irvine, CA) are continuous, noninvasive
blood pressure monitors using a finger-application device. These devices show a
promising ability to allow for rapid detection of hemodynamic derangement when
compared with oscillometry. The accuracy and precision of these devices as blood
pressure monitors has been evaluated when compared with intra-arterial catheters.
Additionally, they can be used to measure beat-to-beat cardiac output (CO). As CO
monitors, they are capable of trending changes in CO when compared with a
transpulmonary thermodilution monitor. Difficulty with use in critically ill and
awake patients has been encountered because of altered microvascular physiology
and patient movement. The principles of operation and clinical validation of
these devices are presented. The clinicians who are interested in using these
devices in their clinical setting should be aware of the relatively large bias
and CIs in the hemodynamic measurements.
PMID- 28490234
TI - Are self-rated and behavioural measures of impulsivity in bipolar disorder mainly
related to comorbid substance use problems?
AB - INTRODUCTION: Impulsivity is a multidimensional feature observed in bipolar
disorder (BD) and substance use disorder (SUD). We previously found a
relationship between SUD and risk taking in BD. It is still unclear whether self
rated and behavioral impulsivity measures differ between BD with and without
comorbid SUD, or are specific to BD. METHODS: 93 adults with BD with comorbid
SUD, 91 BD without SUD, and 93 healthy controls (HC) were administered the
Barratt Impulsivity Scale (BIS), the Behavioral Inhibition/Behavioral Activation
System Scale (BIS/BAS), and the Cambridge Neuropsychological Test Automated
Battery. Analyses compared impulsivity measures across groups controlling for
age. Discriminant function analyses (DFA) assessed the combination of variables
effectively predicting group membership. RESULTS: BD displayed increased BIS,
BIS/BAS scores, reduced performance on the Cambridge Gambling and Rapid Visual
Processing, and Affective Go/No-Go tasks compared to HC. Comparisons between BD
with and without SUD showed increased BIS Motor impulsiveness. The overall
predictive power of DFA was weak. CONCLUSIONS: Some facets of impulsivity are a
core trait of BD and are partially independent from the presence of SUD. Motor
impulsiveness may be distinctive of BD+SUD. More research is needed to understand
the role of impulsive behaviors as risk factors for relapse in SUD.
PMID- 28490235
TI - Aloe Metabolites Prevent LPS-Induced Sepsis and Inflammatory Response by
Inhibiting Mitogen-Activated Protein Kinase Activation.
AB - Aloe, a polyphenolic anthranoid-containing Aloe vera leaves, is a Chinese
medicine and a popular dietary supplement worldwide. In in vivo situations,
polyphenolic anthranoids are extensively broken down into glucuronides and
sulfate metabolites by the gut and the liver. The anti-inflammatory potential of
aloe metabolites has not been examined. The aim of this study was to investigate
the anti-inflammatory effects of aloe metabolites from in vitro
(lipopolysaccharides (LPS)-activated RAW264.7 macrophages) and ex vivo (LPS
activated peritoneal macrophages) to in vivo (LPS-induced septic mice). The
production of proinflammatory cytokines (TNF-[Formula: see text] and IL-12) and
NO was determined by ELISA and Griess reagents, respectively. The expression
levels of iNOS and MAPKs were analyzed by Western blot. Our results showed that
aloe metabolites inhibited the expression of iNOS, decreased the production of
TNF-[Formula: see text], IL-12, and NO, and suppressed the phosphorylation of
MAPKs by LPS-activated RAW264.7 macrophages. In addition, aloe metabolites
reduced the production of NO, TNF-[Formula: see text] and IL-12 by murine
peritoneal macrophages. Furthermore, aloe administration significantly reduced
the NO level and exhibited protective effects against sepsis-related death in LPS
induced septic mice. These results suggest that aloe metabolites exerted anti
inflammatory effects in vivo, and that these effects were associated with the
inhibition of inflammatory mediators. Therefore, aloe could be considered an
effective therapeutic agent for the treatment of sepsis.
PMID- 28490236
TI - Cinnamyl Alcohol, the Bioactive Component of Chestnut Flower Absolute, Inhibits
Adipocyte Differentiation in 3T3-L1 Cells by Downregulating Adipogenic
Transcription Factors.
AB - The extract of chestnut (Castanea crenata var. dulcis) flower (CCDF) has
antioxidant and antimelanogenic properties, but its anti-obesity properties have
not been previously examined. In this study, we tested the effect of CCDF
absolute on adipocyte differentiation by using 3T3-L1 cells and determining the
bioactive component of CCDF absolute in 3T3-L1 cell differentiation. CCDF
absolute (0.1-100[Formula: see text][Formula: see text]g/mL) did not change 3T3
L1 cell viability. At 50[Formula: see text][Formula: see text]g/mL and
100[Formula: see text][Formula: see text]g/mL, the absolute significantly reduced
the accumulation of lipid droplets in 3T3-L1 cells that were induced by culture
in medium containing 3-isobutyl-1-methylxanthine/dexamethasone/insulin (MDI).
GC/MS analysis showed that CCDF absolute contains 10 compounds. Among these
compounds, cinnamyl alcohol (3-phenyl-2-propene-1-ol) dose-dependently inhibited
the increased accumulation of lipid droplets in MDI-contained medium-cultured 3T3
L1 cells at a concentration range of 0.1[Formula: see text][Formula: see
text]g/mL to 10[Formula: see text][Formula: see text]g/mL that did not cause
cytotoxicity in 3T3-L1 cells. The inhibitory effect was significant at 5[Formula:
see text][Formula: see text]g/mL ([Formula: see text] of response in MDI alone
treated state, [Formula: see text]) and 10[Formula: see text][Formula: see
text]g/mL ([Formula: see text] of response in MDI alone-treated state, [Formula:
see text]). Moreover, the enhanced expression of obesity-related proteins
(PPAR[Formula: see text], C/EBP[Formula: see text], SREBP-1c, and FAS) in MDI
medium-cultivated 3T3-L1 cells was significantly attenuated by the addition of
cinnamyl alcohol at 5[Formula: see text][Formula: see text]g/mL and 10[Formula:
see text][Formula: see text]g/mL. These findings demonstrate that cinnamyl
alcohol suppresses 3T3-L1 cell differentiation by inhibiting anti-adipogenesis
related proteins, and it may be a main bioactive component of CCDF absolute,
exerting antidifferentiation action in 3T3-L1 cells. Therefore, cinnamyl alcohol,
as well as CCDF absolute, may be potential candidates for the prevention or
treatment of obesity.
PMID- 28490237
TI - Phytochemistry and Pharmacological Activities of the Genus Swertia
(Gentianaceae): A Review.
AB - Swertia plants have been considered to be medicinal plants useful for the
treatment of various ailments for thousands of years, especially in Asian
countries. This is due to the broad variety of chemical compounds that provide
multiple ligands for bonding to different endogenous biomacromolecules for
patients. Chemical constituents and pharmacological activities of Swertia plants
are summarized in this paper. Approximately 419 metabolites and 40 bioactive
compounds have been reported from 30 Swertia species, including xanthones,
flavonoids, seco-iridiods, iridiods, triterpenoids, alkaloids, volatiles, and
other secondary metabolites. The bioactivities of Swertia plants include
anticarcinogenic, hepatoprotective, anti-oxidant, hypoglycemic, anthelmintic,
antibacterial, antifungal, anti-diabetic, gut, and airways modulatory,
metabolizing isozymes inhibitory, neuroprotective, HIV-I reverse transcriptases
inhibitory, anticholinergic, and CNS-depressant activities, etc. In addition,
biosynthetic pathways of xanthones, and seco-iridiods, two most important
secondary metabolites for Swertia, are elucidated. The xanthones biosynthetic
pathway is a mixed biosynthetic pathway involved the shikimate and the malonate
routes, and the seco-iridoid pathway starts with geraniol derived from IPP which
is produced either via the MEP or the MVA pathway. This review will offer a
reference for future researches on the protection of natural resources, the
investigation of therapeutic basis, new drug development, and so forth. Metabolic
pathways of some crucial active compounds were also discussed in this review.
PMID- 28490238
TI - 22 controlled trials in Education for Primary Care 1990-2015.
PMID- 28490239
TI - Components of Successful Staple Food Fortification Programs: Lessons From Latin
America.
AB - BACKGROUND: There are few effectiveness evaluations of food fortification
programs, and little is known about what makes programs successful. OBJECTIVE: We
examined 3 food fortification programs in Latin America to identify common
features that might explain their success and to draw lessons for program design
and implementation everywhere: The vitamin A fortification of sugar in Guatemala
with impact on vitamin A status of the population, the fortification of a basket
of foods with iron and other micronutrients in Costa Rica with impact on iron
status and anemia in women and children, and the fortification of wheat flour
with folic acid in Chile, which reduced the incidence of neural tube defects.
METHODS: We identified pertinent literature about these preselected programs and
asked regional experts for any additional information. We also conducted
structured interviews of key informants to provide historical and contextual
information. RESULTS: Institutional research capacity and champions of
fortification are features of successful programs in Latin America. We also found
that private/public partnerships (industry, government, academia, and civil
society) might be key for sustainability. To achieve impact, program managers
need to use fortification vehicles that are consumed by the nutritionally
vulnerable and to add bioavailable fortificants at adequate content levels in
order to fill dietary gaps and reduce micronutrient deficiencies. Adequate
monitoring and quality control are essential. CONCLUSIONS: For future programs,
we recommend that the evaluation be specified up-front, including a baseline/end
line and data collection along the program impact pathway to inform needed
improvements and to strengthen causal inferences.
PMID- 28490240
TI - [Body image and body image distortion].
AB - The aim of this literature review is to integrate the results of various studies
regarding body image and body image distortion into a unified framework. The
concept of body image is complex and can be interpreted from multiple points of
view. The first part of the study touches upon different age characteristics,
attentional focus on the body, the early and important role of the body in
identity formation, specific features in adolescence, gender differences, and the
often-observed stability of body image (distortion), which may be present as a
(trait) marker throughout the lifespan. The second part focuses on the
organization of body image. The results of different studies on cognitive
information processing are reviewed, the question of perceptual accuracy is
addressed and the concepts of embodiment are examined. The third topic is body
image distortion. First, the concept is contextualized along different continua,
then discussed in a clinical sense along with the complexity of diagnostic
methods, as well as the state and trait aspects of body image distortion. Orv
Hetil. 2017; 158(19): 723-730.
PMID- 28490241
TI - [Dr. Ferenc Baranyi (1936-2016). Former Minister of Health of Romania].
PMID- 28490242
TI - [Telemetry data based on comparative study of physical activity in patients with
resynchronization device].
AB - INTRODUCTION: The effect of regular physical activity on health is widely
recognized, but several studies have shown its key importance for heart patients.
AIM: The present study aimed to define the PA % values, and to convert them into
metabolic equivalent values (MET), which describes oxygen consumption during
physical activity. METHOD: A total of seventeen patients with heart disease; 3
females and 14 males; age: 57.35 yrs +/- 9.54; body mass 98.71 +/- 9.89 kg;
average BMI 36.69 +/- 3.67 were recruited into the study. The measured values
from Cardiac Resynchronisation Therapy devices and outer accelerometers
(ActiGraph GT3X+) were studied over a 7-day time period. Using the two sets of
values describing physical performance, linear regression was calculated
providing a mathematical equation, thus, the Physical Activity values in
percentage were converted into MET values. RESULTS: During the 6-minute walk test
the patients achieved an average of 416.6 +/- 48.2 m. During 6MWT the measured
values averaged at 1.85 +/- 0.18 MET's, and MET values averaged at 1.12 +/- 0.06
per week. It clearly shows that this test is a challenge for the patients
compared to their daily regular physical activity levels. CONCLUSION: With our
method, based on the values received from the physical activity sensor implanted
into the resynchronisation devices, changes in patients' health status could be
monitored telemetrically with the assistance from the implanted electronic
device. Orv Hetil. 2017; 158(17): 748-753.
PMID- 28490244
TI - [Investigating the efficacy of nutrition therapy for outpatients with
inflammatory bowel disease].
AB - INTRODUCTION: Inflammatory bowel diseases can cause malnutrition (due to
inflammatory cytokine production, catabolic states after surgery, restricted
diet), which is difficult to treat by nutritional therapy. AIM: Investigating the
efficacy of nutrition therapy. METHOD: Combined malnutrition risk screening
(questionnaires and body composition analysis), at the beginning of the research
and after a 1 year period. RESULTS: 205 patients were screened, 82 were
malnourished. A total of 44 received nutritional intervention for 1 year, for 45%
dietary management was satisfactory, 50% needed oral nutritional supplements and
5% received home parenteral nutrition. These interventions reduced the number of
patients considered by both measuring methods in high risk from 31 to 21,
increased the body weight and fat-free mass in 8 and 9 cases significantly (i.e.,
with more than 10%), and improved the indices as well (DeltaBMI: +1.3 kg/m2, p =
0.035 s., DeltaFFMI: +0.5 kg/m2, p = 0.296 n.s.). The main limitations of our
research are the relatively low number of cases and the mono-centric involvement.
CONCLUSIONS: We recommend combined malnutrition risk screening for all patients
with inflammatory bowel disease due to the high risk of malnutrition, and follow
up of the malnourished patients to monitor the efficacy of their nutrition
therapy. Orv Hetil. 2017; 158(19): 731-739.
PMID- 28490245
TI - [Childhood traumatization, dissociation and nonsuicidal self-injurious behavior
in borderline personality disorder].
AB - INTRODUCTION: Childhood traumatization plays a significant role in the etiology
of borderline personality disorder. Studies found a significant association
between childhood traumatization, dissociation, and nonsuicidal self-injurious
behavior. AIM: The aim of our study was to assess dissociation and nonsuicidal
self-injury among borderline inpatients and to reveal the association between
childhood traumatization, dissociation, and self-injurious behavior. METHOD: The
sample consisted of 80 borderline inpatients and 73 depressed control patients.
Childhood traumatization, dissociation and self-injurious behavior were assessed
by questionnaires. RESULTS: Borderline patients reported severe and multiplex
childhood traumatization. Cumulative trauma score and sexual abuse were the
strongest predictors of dissociation. Furthermore, we have found that cumulative
trauma score and dissociation were highly predictive of self-injurious behavior.
CONCLUSION: Our results suggest that self-injurious behavior and dissociation in
borderline patients can be regarded as indicators of childhood traumatization.
Orv Hetil. 2017; 158(19): 740-747.
PMID- 28490246
TI - Evaluation of Xpert MTB/RIF assay in children with presumed pulmonary
tuberculosis in Papua New Guinea.
AB - BACKGROUND: The Gene Xpert MTB/ RIF assay (Xpert) is used for rapid, simultaneous
detection of Mycobacterium tuberculosis (MTB) and rifampicin resistance. This
study examined the accuracy of Xpert in children with suspected pulmonary
tuberculosis (PTB). METHODS: Children admitted to Port Moresby General Hospital
with suspected PTB were prospectively enrolled between September 2014 and March
2015. They were classified into probable, possible and TB-unlikely groups. Sputum
or gastric aspirates were tested by Xpert and smear microscopy; mycobacterial
culture was undertaken on a subset. Children were diagnosed with TB on the basis
of standard criteria which were used as the primary reference standard. Xpert,
smear for acid-fast bacilli (AFB) and the Edwards TB score were compared with the
primary reference standard. RESULTS: A total of 93 children <=14 years with
suspected PTB were enrolled; 67 (72%) were classified as probable, 21 (22%)
possible and 5 (5.4%) TB-unlikely. Eighty were treated for TB based on the
primary reference standard. Xpert was positive in 26/93 (28%) MTB cases overall,
including 22/67 (33%) with probable TB and 4/21 (19%) with possible TB. Three
(13%) samples identified rifampicin resistance. Xpert confirmed more cases of TB
than AFB smear (26 vs 13, p = 0.019). The sensitivity of Xpert, AFB smear and an
Edwards TB score of >=7 was 31% (25/80), 16% (13/80) and 90% (72/80),
respectively, and the specificity was 92% (12/13), 100% (13/13) and 31% (4/13),
respectively, when compared with the primary reference standard. CONCLUSION:
Xpert sensitivity is sub-optimal and cannot be relied upon for diagnosing TB,
although a positive result is confirmatory. A detailed history and examination,
standardised clinical criteria, radiographs and available tests remain the most
appropriate way of diagnosing TB in children in resource-limited countries. Xpert
helps confirm PTB better than AFB smear, and identifies rifampicin resistance.
Practical guidelines should be used to identify children who will benefit from an
Xpert assay.
PMID- 28490247
TI - Effects of valent image-based secondary tasks on verbal working memory.
AB - Two experiments examined if exposure to emotionally valent image-based secondary
tasks introduced at different points of a free recall working memory (WM) task
impair memory performance. Images from the International Affective Picture System
(IAPS) varied in the degree of negative or positive valance (mild, moderate,
strong) and were positioned at low, moderate and high WM load points with
participants rating them based upon perceived valence. As predicted, and based on
previous research and theory, the higher the degree of negative (Experiment 1)
and positive (Experiment 2) valence and the higher the WM load when a secondary
task was introduced, the greater the impairment to recall. Secondary task images
with strong negative valance were more disruptive than negative images with lower
valence at moderate and high WM load task points involving encoding and/or
rehearsal of primary task words (Experiment 1). This was not the case for
secondary tasks involving positive images (Experiment 2), although participant
valence ratings for positive IAPS images classified as moderate and strong were
in fact very similar. Implications are discussed in relation to research and
theory on task interruption and attentional narrowing and literature concerning
the effects of emotive stimuli on cognition.
PMID- 28490249
TI - Novel single marker approach to estimation of lower extremity movement.
AB - Sacrum motion is used extensively in studying the biomechanical characteristics
of walking. This study aimed at investigating the potential of sacrum motion to
provide an estimation of important gait events in conjunction with predicting the
motion of lower extremity segments. Three-dimensional trajectories of 37
reflective markers placed on anatomical landmarks of 14 healthy subjects were
recorded while walking at self-selected normal walking speed on treadmill.
Elevation angles of lower extremity segments in sagittal plane were estimated
using the lower extremity markers. Regression analysis was used to estimate the
ability of sacrum kinematic variables to predict lower extremity elevation
angles. Prediction was performed at 10 different gait events extracted from three
dimensional sacrum trajectories. The coefficients of the predicting variables
were analyzed at these events. The results indicated that heel strike and toe off
event instances identified using trajectory of sacrum marker were close to the
results of accurate kinematic methods. Additionally, the motion of this point was
able to predict lower extremity angles with a suitable coefficient of
determination at early single support and mid-swing events. A range of
musculoskeletal disorders could be identified using the elevation angles at these
events. This study could be considered as a step toward development of effective
and simplified instrumentation in clinical diagnosis of gait disorders.
PMID- 28490248
TI - Sodium louroyl sarcosinate (sarkosyl) modulate amyloid fibril formation in hen
egg white lysozyme (HEWL) at alkaline pH: a molecular insight study.
AB - Amyloid fibril formation is responsible for several neurodegenerative diseases
and are formed when native proteins misfold and stick together with different
interactive forces. In the present study, we have determined the mode of
interaction of the anionic surfactant sarkosyl with hen egg white lysozyme (HEWL)
[EC No. 3.2.1.17] at two pHs (9.0 and 13.0) and investigated its impact on
fibrillogenesis. Our data suggested that sarkosyl is promoting amyloid fibril
formation in HEWL at the concentration range between 0.9 and 3.0 mM and no
amyloid fibril formation was observed in the concentration range of 3.0-20.0 mM
at pH 9.0. The results were confirmed by several biophysical and computational
techniques, such as turbidity measurement, dynamic light scattering, Raleigh
scattering, ThT fluorescence, intrinsic fluorescence, far-UV CD and atomic force
microscopy. Sarkosyl was unable to induce aggregation in HEWL at pH 13.0 as
confirmed by turbidity and RLS measurements. HEWL forms larger amyloid fibrils in
the presence of 1.6 mM of sarkosyl. The spectroscopic, microscopic and molecular
docking data suggest that the negatively charged carboxylate group and 12-carbon
hydrophobic tail of sarkosyl stimulate amyloid fibril formation in HEWL via
electrostatic and hydrophobic interaction. This study leads to new insight into
the process of suppression of fibrillogenesis in HEWL which can be prevented by
designing ligands that can retard the electrostatic and hydrophobic interaction
between sarkosyl and HEWL.
PMID- 28490250
TI - Effects of acrylamide graded doses on metallothioneins I and II induction and DNA
fragmentation: Bochemical and histomorphological changes in the liver of adult
rats.
AB - The present study investigates the toxic effects of acrylamide (ACR) administered
to rats at two doses on (i) oxidative stress and disruption of pro
oxidant/antioxidant balance in hepatic cells and (ii) its correlation with
metallothioneins (MTs) genes expression, DNA damage and histomorphological
changes. Treated rats with 20 and 40 mg/kg body weight of ACR led to an increase
in malondialdehyde, hydrogen peroxide, advanced oxidation protein products,
protein carbonyl levels as well as an alteration in the antioxidant status. Total
MT content in the liver and MT I and MT II genes induction were increased. Plasma
transaminases activities, albumin, total protein and glucose levels were also
increased, while alkaline phosphatase activity was decreased. Moreover, total
cholesterol (TC), triglyceride, low-density lipoprotein cholesterol (LDL-C)
levels, TC/high-density lipoprotein cholesterol (HDL-C) and LDL-C/HDL-C ratios
were increased, while HDL-C decreased in a dose-dependent manner. A random DNA
degradation was observed only in the liver of ACR-treated rats with the highest
dose. These changes were confirmed by histopathological observations.
PMID- 28490251
TI - Ampicillin-incorporated alginate-chitosan fibers from microfluidic spinning and
for vitro release.
AB - The fibrous drug-loading capability, degradation profile, drug release behavior
and mechanical performance were found to be controlled by regulating the amount
of IPA and chitosan, which delayed the degradable time-scale and improved the
drug loading capacity. Six types of alginate fibers were spun by combining two
distinct core flows with deionized water-based, ethanol-based and isopropyl
alcohol-based sheath fluid, respectively. The as prepared fibers were analyzed
and compared by the characterization of SEM, mass loss, ICP, FTIR, XRD, UV,
mechanics performance testing and antibacterial activity tests. The results
showed that fibers in the isopropyl alcohol with low polarity sheath flow
exhibited higher-ordered structure. Also, incorporation of chitosan for the core
stream strengthened the degree of crosslinking among the molecular chain, and
thus made the fiber entrapped more drug of ampicillin molecular. The fibers,
possessing superior mechanical properties, preferable drug loading capability,
more prolonged drug release behavior and outstanding antibiotic activity, may
offer a promising candidate for biomaterials, such as fibrous drug carrier and
antibacterial sutures.
PMID- 28490252
TI - Visceral leishmaniosis in immunocompromised host: an update and literature
review.
AB - Visceral leishmaniasis (VL) is a chronic infectious disease endemic in tropical
and sub-tropical areas including the Mediterranean basin, caused by a group of
protozoan parasites of the genus Leishmania and transmitted by phlebotomine
sandflies. Immunocompromised patients, in particular HIV positive, are considered
at risk of VL. They report atypical signs and poor response to treatment due to
impairment of T-helper and regulatory cells activity. Laboratory diagnosis is
based on microscopy on bone marrow or spleen aspirates. Value of serology remains
high in term of sensibility, but a positive test must be confirmed by microscopy
or molecular tests. Treatment is based on Liposomal amphotericin B whose
administration is associated to lower incidence of side effects, in respect to
antimonials and other formulations of AmB. Use of Miltefosine needs further
investigation when L. infantum is the causative agent. Frequent relapses are
observed in co-infected HIV who can benefit of a second cycle.
PMID- 28490253
TI - Science to the rescue or contingent progress? Comparing 10 years of public,
expert and policy discourses on new and emerging science and technology in the
United Kingdom.
AB - Over the past 10 years, numerous public debates on new and emerging science and
technologies have taken place in the United Kingdom. In this article, we
characterise the discourses emerging from these debates and compare them to the
discourses in analogous expert scientific and policy reports. We find that while
the public is broadly supportive of new scientific developments, they see the
risks and social and ethical issues associated with them as unpredictable but
inherent parts of the developments. In contrast, the scientific experts and
policymakers see risks and social and ethical issues as manageable and
quantifiable with more research and knowledge. We argue that these differences
amount to two different sociotechnical imaginaries or views of science and how it
shapes our world - an elite imaginary of 'science to the rescue' shared by
scientists and policymakers and public counter-imaginary of 'contingent
progress'. We argue that these two imaginaries indicate that, but also help
explain why, public dialogue has had limited impact on public policy.
PMID- 28490254
TI - Validating Dose Uncertainty Estimates Produced by AUTODIRECT: An Automated
Program to Evaluate Deformable Image Registration Accuracy.
AB - Deformable image registration is a powerful tool for mapping information, such as
radiation therapy dose calculations, from one computed tomography image to
another. However, deformable image registration is susceptible to mapping errors.
Recently, an automated deformable image registration evaluation of confidence
tool was proposed to predict voxel-specific deformable image registration dose
mapping errors on a patient-by-patient basis. The purpose of this work is to
conduct an extensive analysis of automated deformable image registration
evaluation of confidence tool to show its effectiveness in estimating dose
mapping errors. The proposed format of automated deformable image registration
evaluation of confidence tool utilizes 4 simulated patient deformations (3 B
spline-based deformations and 1 rigid transformation) to predict the uncertainty
in a deformable image registration algorithm's performance. This workflow is
validated for 2 DIR algorithms (B-spline multipass from Velocity and Plastimatch)
with 1 physical and 11 virtual phantoms, which have known ground-truth
deformations, and with 3 pairs of real patient lung images, which have several
hundred identified landmarks. The true dose mapping error distributions closely
followed the Student t distributions predicted by automated deformable image
registration evaluation of confidence tool for the validation tests: on average,
the automated deformable image registration evaluation of confidence tool
produced confidence levels of 50%, 68%, and 95% contained 48.8%, 66.3%, and 93.8%
and 50.1%, 67.6%, and 93.8% of the actual errors from Velocity and Plastimatch,
respectively. Despite the sparsity of landmark points, the observed error
distribution from the 3 lung patient data sets also followed the expected error
distribution. The dose error distributions from automated deformable image
registration evaluation of confidence tool also demonstrate good resemblance to
the true dose error distributions. Automated deformable image registration
evaluation of confidence tool was also found to produce accurate confidence
intervals for the dose-volume histograms of the deformed dose.
PMID- 28490255
TI - Developing a taxonomy of coordination behaviours in nuclear power plant control
rooms during emergencies.
AB - This study aims to develop a taxonomy of coordination behaviours during
emergencies in nuclear power plants (NPPs). We summarised basic coordination
behaviours from literature in aviation, health care and nuclear field and
identified coordination behaviours specific to the nuclear domain by interviewing
and surveying control crew operators. The established taxonomy includes 7
workflow stages and 24 basic coordination behaviours. To evaluate the reliability
and feasibility of the taxonomy, we analysed 12 videos of operators' training
sessions by coding coordination behaviours with the taxonomy and the inter-rater
reliability was acceptable. Further analysis of the frequency, the duration and
the direction of the coordination behaviours revealed four coordination problems.
This taxonomy provides a foundation of systematic observation of coordination
behaviours among NPP crews, advances researchers' understanding of the
coordination mechanism during emergencies in NPPs and facilitate the possibility
to deepen the understanding of the relationships between coordination behaviours
and team performance. Practitioner Summary: A taxonomy of coordination behaviours
during emergencies in nuclear power plants was developed. Reliability and
feasibility of the taxonomy was verified through the analysis of 12 training
sessions. The taxonomy can serve as an observation system for analysis of
coordination behaviours and help to identify coordination problems of control
crews.
PMID- 28490257
TI - Tissue distribution and elimination of deoxynivalenol and ochratoxin A in dietary
exposed Atlantic salmon (Salmo salar).
AB - Post-smolt Atlantic salmon (Salmo salar) were fed standard feed with added 2 or 6
mg kg-1 pure deoxynivalenol (DON), 0.8 or 2.4 mg kg-1 pure ochratoxin A (OTA), or
no added toxins for up to 8 weeks. The experiments were performed in duplicate
tanks with 25 fish each per diet group, and the feed was given for three 2-h
periods per day. After 3, 6 and 8 weeks, 10 fish from each diet group were
sampled. In the following hours after the last feeding at 8 weeks, toxin
elimination was studied by sampling three fish per diet group at five time
points. Analysis of DON and OTA in fish tissues and plasma was conducted by
liquid chromatography-mass spectrometry and high-pressure liquid chromatography
with fluorescence detection, respectively. DON was distributed to the liver,
kidney, plasma, muscle, skin and brain, and the concentrations in liver and
muscle increased significantly from 3 to 8 weeks of exposure to the high-DON
diet. After the last feeding at 8 weeks, DON concentration in liver reached a
maximum at 1 h and decreased thereafter with a half-life (t1/2) of 6.2 h. DON
concentration in muscle reached a maximum at 6 h and was then eliminated with a
t1/2 = 16.5 h. OTA was mainly found in liver and kidney, and the concentration in
liver decreased significantly from 3 to 8 weeks in the high-OTA group. OTA was
eliminated faster than DON from various tissues. By using Norwegian food
consumption data and kinetic findings in this study, we predicted the human
exposure to DON and OTA from fish products through carryover from the feed.
Following a comparison with tolerable daily intakes, we found the risk to human
health from the consumption of salmon-fed diets containing maximum recommended
levels of these toxins to be negligible.
PMID- 28490258
TI - Trophic Effects of Mesenchymal Stem Cells in Tissue Regeneration.
AB - Mesenchymal stem cells (MSCs) are considered to hold great therapeutic value for
cell-based therapy and for tissue regeneration in particular. Recent evidence
indicates that the main underlying mechanism for MSCs' beneficial effects in
tissue regeneration is based on their capability to produce a large variety of
bioactive trophic factors that stimulate neighboring parenchymal cells to start
repairing damaged tissues. These new findings could potentially replace the
classical paradigm of MSC differentiation and cell replacement. These bioactive
factors have diverse actions like modulating the local immune system, enhancing
angiogenesis, preventing cell apoptosis, and stimulating survival, proliferation,
and differentiation of resident tissue specific cells. Therefore, MSCs are
referred to as conductors of tissue repair and regeneration by secreting trophic
mediators. In this review article, we have summarized the studies that focused on
the trophic effects of MSC within the context of tissue regeneration. We will
also highlight the various underlying mechanisms used by MSCs to act as trophic
mediators. Besides the secretion of growth factors, we discuss two additional
mechanisms that are likely to mediate MSC's beneficial effects in tissue
regeneration, namely the production of extracellular vesicles and the formation
of membrane nanotubes, which can both connect different cells and transfer a
variety of trophic factors varying from proteins to mRNAs and miRNAs.
Furthermore, we postulate that apoptosis of the MSCs is an integral part of the
trophic effect during tissue repair.
PMID- 28490256
TI - How Plastic Are Pericytes?
AB - Pericytes are defined by both their anatomical location and molecular markers.
Numerous publications have reported their role as stem cells, contributing to the
formation of tissues other than blood vessels. However, using cell-lineage
tracing in a new transgenic mouse model, a recent study shows that in the context
of aging and some pathologies, Tbx18+ pericytes do not function as stem cells in
vivo. This study challenges the current view that pericytes can differentiate
into other cells and reopen questions about their plasticity. This emerging
knowledge is important not only for our understanding of development but may also
inform treatments for diseases.
PMID- 28490259
TI - Recent amendments to NICE's value-based assessment of health technologies:
implicitly inequitable?
PMID- 28490260
TI - Emerging treatments for Alzheimer's disease for non-amyloid and non-tau targets.
AB - INTRODUCTION: The number of people with dementia, including Alzheimer's disease,
is growing as a result of an ageing global population. Treatments available for
AD only alleviate the symptoms of the disease, and are effective in some people
with AD for a limited time. There is no disease-modifying treatment available,
and despite research efforts, the underlying mechanisms of AD and optimal
treatment targets have not been fully elucidated. Amyloid and tau are key
pathological markers of AD with ongoing trials targeting both. However, there are
also many trials at various stages of development that primarily target other
markers and processes implicated in the disease, which are now being
investigated. Areas covered: This review summarizes current treatment approaches
for AD and explores both repositioned and novel therapies that target non amyloid
and non tau mechanisms that are in the clinical trials pipeline. This includes
treatments for cognitive and neuropsychiatric symptoms and potentially disease
modifying therapies. The studies included in this review have been obtained from
searches of PubMed and clinical trials databases. Expert commentary: There is a
renewed energy in identifying better treatments for behavioural symptoms of AD
using both novel drugs and repositioning existing drugs. Lack of success in
clinical trials of drugs targeting amyloid and tau have led to a surge in
targeting alternative mechanisms. Progress in the development of biomarkers will
provide further tools for clinical trials of potential therapeutics for both
symptomatic treatment and disease modification in AD.
PMID- 28490261
TI - Prognostic factors associated with 30-day in-hospital mortality in coagulase
negative Staphylococcus bacteraemia: no impact of vancomycin minimum inhibitory
concentration.
AB - BACKGROUND: The impact of a minimum inhibitory concentration (MIC) of vancomycin
>=2 mg/L on mortality and the potential benefit of new antistaphylococcal
treatments in coagulase-negative Staphylococcus (CoNS) bacteraemia remain
unknown. We assessed the impact of vancomycin MIC on 30-day in-hospital mortality
and identified factors independently associated with 30-day in-hospital
mortality. METHODS: All patients presenting significant CoNS bacteraemia in the
university hospital of Reims, between 01 January 2008 and 31 December 2012, were
included. Data were retrospectively extracted from the patient records.
Vancomycin MIC was assessed using the E-test method, and antimicrobial
susceptibility testing was performed in accordance with the recommendations of
the Antibiogram Committee of the French Microbiology Society. Cox's Proportional
Hazards model was used for multivariate analysis. RESULTS: Two hundred and sixty
nine patients (mean age 61.2 +/- 15.7 years) were included. Foreign material was
present in 92% of patients and 78.4% of isolated methicillin-resistant strains
had vancomycin MIC >=2 mg/l. Thirty-day in-hospital mortality was 16%. There was
no association between vancomycin MIC >=2 mg/l and 30-day in-hospital mortality
(adjusted Hazard Ratio (aHR) = .80, 95% confidence interval (95%CI) [.30-2.19], p
= .67). Factors independently associated with 30-day in-hospital mortality were
age >=75 vs. <=60 years (aHR =3.72, 95%CI [1.39-9.97], p = .009), absence of
active antibiotic treatment (aHR =5.52, 95%CI [1.13-26.87], p = .03) and acute
renal failure (aHR =4.45, 95%CI [2.08-9.56], p < .0001). Removal of an infected
device had a protective effect against 30-day in-hospital mortality (aHR = .23,
95%CI [.11-.48], p < .0001). CONCLUSIONS: These results suggest that CoNS
bacteraemia should be managed by removal of the infected device and antibiotic
treatment such as vancomycin.
PMID- 28490263
TI - Results of primary end-to-side digital nerve neurorrhaphy in eight patients.
PMID- 28490262
TI - Methods for safety signal detection in healthcare databases: a literature review.
AB - INTRODUCTION: With increasing availability, the use of healthcare databases as
complementary data source for drug safety signal detection has been explored to
circumvent the limitations inherent in spontaneous reporting. Areas covered: To
review the methods proposed for safety signal detection in healthcare databases
and their performance. Expert opinion: Fifteen different data mining methods were
identified. They are based on disproportionality analysis, traditional
pharmacoepidemiological designs (e.g. self-controlled designs), sequence symmetry
analysis (SSA), sequential statistical testing, temporal association rules,
supervised machine learning (SML), and the tree-based scan statistic. When
considering the performance of these methods, the self-controlled designs, the
SSA, and the SML seemed the most interesting approaches. In the perspective of
routine signal detection from healthcare databases, pragmatic aspects such as the
need for stakeholders to understand the method in order to be confident in the
results must be considered. From this point of view, the SSA could appear as the
most suitable method for signal detection in healthcare databases owing to its
simple principle and its ability to provide a risk estimate. However, further
developments, such as automated prioritization, are needed to help stakeholders
handle the multiplicity of signals.
PMID- 28490264
TI - Effects of metabolic syndrome on the functional outcomes of corticosteroid
injection for De Quervain tenosynovitis.
AB - : Metabolic syndrome is a constellation of medical conditions that arise from
insulin resistance and abnormal adipose deposition and function. In patients with
metabolic syndrome and De Quervain tenosynovitis this might affect the outcome of
treatment by local corticosteroid injection. A total of 64 consecutive patients
with De Quervain tenosynovitis and metabolic syndrome treated with corticosteroid
injection were age- and sex-matched with 64 control patients without metabolic
syndrome. The response to treatment, including visual analogue scale score for
pain, objective findings consistent with De Quervain tenosynovitis (tenderness at
first dorsal compartment, Finkelstein test result), and Disability of the Arm,
Shoulder, and Hand score were assessed at 6, 12, and 24 weeks follow-up.
Treatment failure was defined as persistence of symptoms or surgical
intervention. Prior to treatment, patients with metabolic syndrome had mean
initial pain visual analogue scale and Disability of the Arm, Shoulder, and Hand
scores similar to those in the control group. The proportion of treatment failure
in the metabolic syndrome group (43%) was significantly higher than that in the
control group (20%) at 6 months follow-up. The pain visual analogue scale scores
in the metabolic syndrome group were higher than the scores in the control group
at the 12- and 24-week follow-ups. The Disability of the Arm, Shoulder, and Hand
scores of the metabolic syndrome group were higher (more severe symptoms) than
those of the control group at the 12- and 24-week follow-ups. Although
considerable improvements in symptom severity and hand function will likely occur
in patients with metabolic syndrome, corticosteroid injection for De Quervain
tenosynovitis is not as effective in these patients compared with age- and sex
matched controls in terms of functional outcomes and treatment failure. LEVEL OF
EVIDENCE: III.
PMID- 28490265
TI - Crush asphyxia and ride-on lawn mowers.
AB - Search of files at Forensic Science SA, Australia, over the past 20 years (1997
2016) revealed three cases of death due to crush asphyxia associated with the use
of ride-on lawn mowers. (1) A 61-year-old man was trapped under a ride-on mower
that had rolled over. Autopsy examination revealed congestion and petechial
haemorrhages of the face and chest, and markings on the chest associated with
underlying rib fractures. (2) A 78-year-old man was trapped under a ride-on mower
that had also rolled over. Autopsy examination revealed petechial haemorrhages of
the face and chest and markings on the chest. (3) A 72-year-old man was found
wedged between a ride-on mower and a tree, with petechial haemorrhages of the
face and chest, and markings on the front and back of the chest. These cases
demonstrate a rare cause of crush asphyxia, often in older males in the domestic
environment, which may arise from more than one mechanism.
PMID- 28490266
TI - Radiotherapy in Dupuytren's disease: a systematic review of the evidence.
AB - : Radiotherapy has been advocated as an alternative treatment in early
Dupuytren's disease. We have systematically reviewed the evidence on the use of
radiotherapy in Dupuytren's disease. Only six articles met a minimum set
standard, five of which were retrospective cohort studies and one a randomized
controlled study. A total of 770 Dupuytren's hands, nearly all with Tubiana stage
0-1 disease, were irradiated with an average 30 Gy. Disease regression ranged
from 0%-56%, stability from 14%-98% and progression from 2%-86%. Salvage surgery
was successful in all cases of disease progression post-radiotherapy. There were
no reports of adverse wound healing problems associated with such surgery or
radiotherapy-associated malignancy. On balance, radiotherapy should be considered
an unproven treatment for early Dupuytren's disease due to a scarce evidence base
and unknown long-term adverse effects. Well-designed randomized controlled
studies are required to confirm the benefits of radiotherapy treatment. LEVEL OF
EVIDENCE: II.
PMID- 28490267
TI - Darolutamide (ODM-201) for the treatment of prostate cancer.
AB - INTRODUCTION: Androgen deprivation therapy (ADT) is a mainstay initial treatment
for advanced hormone-sensitive prostate cancer (HSPC), but disease progression to
castration-resistant prostate cancer (CRPC) invariably occurs when patients do
not succumb to another disease or comorbidity. Recognition that the androgen
receptor (AR) axis continues to drive disease progression has led to the
development of several AR-directed approved agents, including abiraterone acetate
and enzalutamide. An investigational agent, darolutamide (ODM-201, BAY-1841788),
has completed early-phase clinical trials, and two global phase III trials are
currently accruing patients. Areas covered: The unmet clinical need,
pharmacokinetics, preclinical development, and clinical efficacy and safety of
darolutamide for the treatment of advanced prostate cancer are reviewed. The
design of two ongoing phase III trials (ARAMIS and ARASENS) of darolutamide in
men with non-metastatic CRPC and metastatic HSPC, respectively, are also
discussed. Expert opinion: Darolutamide is an oral, investigational, high
affinity AR antagonist which has activity against known AR mutants that confer
resistance to other second-generation antiandrogens, has minimal blood-brain
barrier penetration, and does not significantly increase serum testosterone.
These features may offer potential advantages over the second-generation
antiandrogens. In the phase I/II ARADES trial, darolutamide demonstrated
promising antitumor activity and a favorable safety profile in men with
metastatic CRPC.
PMID- 28490268
TI - More than meets the MRI: case report of a carcinoid tumour metastasis mimicking a
meningioma.
AB - Cerebral metastases from carcinoid tumours are rarely reported and confer a much
poorer prognosis than carcinoid metastases elsewhere in the body. We describe a
case of carcinoid brain metastasis closely resembling a meningioma on magnetic
resonance imaging (MRI), and review current treatment options.
PMID- 28490269
TI - Investigations of FAK inhibitors: a combination of 3D-QSAR, docking, and
molecular dynamics simulations studies.
AB - Focal adhesion kinase (FAK) is one kind of tyrosine kinases that modulates
integrin and growth factor signaling pathways, which is a promising therapeutic
target because of involving in cancer cell migration, proliferation, and
survival. To investigate the mechanism between FAK and triazinic inhibitors and
design high activity inhibitors, a molecular modeling integrated with 3D-QSAR,
molecular docking, molecular dynamics simulations, and binding free energy
calculations was performed. The optimum CoMFA and CoMSIA models showed good
reliability and satisfactory predictability (with Q2 = 0.663, R2 = 0.987,
[Formula: see text] = 0.921 and Q2 = 0.670, R2 = 0.981, [Formula: see text] =
0.953). Its contour maps could provide structural features to improve inhibitory
activity. Furthermore, a good consistency between contour maps, docking, and
molecular dynamics simulations strongly demonstrates that the molecular modeling
is reliable. Based on it, we designed several new compounds and their inhibitory
activities were validated by the molecular models. We expect our studies could
bring new ideas to promote the development of novel inhibitors with higher
inhibitory activity for FAK.
PMID- 28490270
TI - Change-point detection for infinite horizon dynamic treatment regimes.
AB - A dynamic treatment regime is a set of decision rules for how to treat a patient
at multiple time points. At each time point, a treatment decision is made
depending on the patient's medical history up to that point. We consider the
infinite-horizon setting in which the number of decision points is very large.
Specifically, we consider long trajectories of patients' measurements recorded
over time. At each time point, the decision whether to intervene or not is
conditional on whether or not there was a change in the patient's trajectory. We
present change-point detection tools and show how to use them in defining dynamic
treatment regimes. The performance of these regimes is assessed using an
extensive simulation study. We demonstrate the utility of the proposed change
point detection approach using two case studies: detection of sepsis in preterm
infants in the intensive care unit and detection of a change in glucose levels of
a diabetic patient.
PMID- 28490273
TI - Corrigendum.
PMID- 28490272
TI - Transfer of the musculocutaneous nerve branch to the brachialis muscle to the
triceps for elbow extension: anatomical study and report of five cases.
AB - : We report the study of the anatomical feasibility of transferring the nerve to
the brachialis muscle to the upper medial head motor branch that innervate the
triceps, and outcomes of such transfers in restoring elbow extension in five
patients with posterior cord lesion of the brachial plexus. The length of the
branches to the brachialis muscle measured 7.6 cm and the triceps upper medial
head motor branch was 5 cm in 10 adult cadavers. Five male patients were treated
with this transfer 5 months after the injury (range 4 to 6 months) after
posterior cord injury of the brachial plexus with a mean follow-up of 31 months
(range 28 to 36 months). Elbow extension scored M4 in all cases. No complications
occurred. These preliminary results suggest that transferring the nerve to the
brachialis muscle is an effective technique for the reconstruction of elbow
extension after posterior cord brachial plexus injuries. LEVEL OF EVIDENCE: IV.
PMID- 28490271
TI - Validation of a Cardiovascular Disease Policy Microsimulation Model Using Both
Survival and Receiver Operating Characteristic Curves.
AB - BACKGROUND: Despite some advances, cardiovascular disease (CVD) remains the
leading cause of death and healthcare costs in the United States. We therefore
developed a comprehensive CVD policy simulation model that identifies cost
effective approaches for reducing CVD burden. This paper aims to: 1) describe our
model in detail; and 2) perform model validation analyses. METHODS: The model
simulates 1,000,000 adults (ages 35 to 80 years) using a variety of CVD-related
epidemiological data, including previously calibrated Framingham-based risk
scores for coronary heart disease and stroke. We validated our microsimulation
model using recent National Health and Nutrition Examination Survey (NHANES)
data, with baseline values collected in 1999-2000 and cause-specific mortality
follow-up through 2011. Model-based (simulated) results were compared to observed
all-cause and CVD-specific mortality data (from NHANES) for the same starting
population using survival curves and, in a method not typically used for disease
model validation, receiver operating characteristic (ROC) curves. RESULTS:
Observed 10-year all-cause mortality in NHANES v. the simulation model was 11.2%
(95% CI, 10.3% to 12.2%) v. 10.9%; corresponding results for CVD mortality were
2.2% (1.8% to 2.7%) v. 2.6%. Areas under the ROC curves for model-predicted 10
year all-cause and CVD mortality risks were 0.83 (0.81 to 0.85) and 0.84 (0.81 to
0.88), respectively; corresponding results for 5-year risks were 0.80 (0.77 to
0.83) and 0.81 (0.75 to 0.87), respectively. LIMITATIONS: The model is limited by
the uncertainties in the data used to estimate its input parameters.
Additionally, our validation analyses did not include non-fatal CVD outcomes due
to NHANES data limitations. CONCLUSIONS: The simulation model performed well in
matching to observed nationally representative longitudinal mortality data. ROC
curve analysis, which has been traditionally used for risk prediction models, can
also be used to assess discrimination for disease simulation models.
PMID- 28490274
TI - Masked primes evoke partial responses.
AB - Backward-masked primes presented outside conscious awareness can affect responses
to subsequently presented target stimuli. Differences in response times have been
used to infer a pattern of sub-threshold activation and subsequent inhibition of
motor plans associated with the primes. However, it is unclear whether
competition between alternative responses is fully resolved in the brain or
whether activated responses can begin being executed before the final decision to
act has been made. Here, we investigate the dynamics of responses evoked by
masked primes using a continuous measure - voltage change in force-sensing
resistors simultaneously in both hands. Masked primes produced the predicted
pattern of motor activation and subsequent inhibition of the primed response.
There is no evidence that the effects of masked primes interact with spatial
compatibility (e.g., Simon) effects, suggesting separate mechanisms underpinning
these effects. Moreover, masked primes evoked partial motor decisions -
measurable at the effectors as small amounts of erroneous response - which were
usually rapidly corrected. Together, these errors and fast corrections question
the 'sub-threshold' nature of responses evoked by masked primes and provide
important constraints on models of decision-making.
PMID- 28490275
TI - Genome-wide sequential, evolutionary, organizational and expression analyses of
phenylpropanoid biosynthesis associated MYB domain transcription factors in
Arabidopsis.
AB - The MYB gene family represents one of the largest groups of transcription factors
in plants. Recent evidences have also demonstrated key role of MYB transcription
factors in regulating the expression of major genes involved in the biosynthesis
of phenylpropanoid compounds which confer biotic and abiotic stress tolerance in
plant species. However, no comprehensive genome-wide analysis of the
phenylpropanoid pathway-associated MYB transcription factors has been reported
thus far. In this study, 11 Arabidopsis MYB proteins, such as MYB3, MYB4, MYB7,
MYB11, MYB12, MYB32, MYB75, MYB90, MYB111, MYB113, and MYB114 were initially
identified considering their reported regulatory function in phenylpropanoid
biosynthesis pathway. Subsequent genome-wide analysis have identified the
corresponding homologues from Glycine max, Vigna radiata, Oryza sativa, and Zea
mays, while homologous of Arabidopsis MYB75, MYB90, MYB113, and MYB114 were not
detected in rice and maize genomes. The identified MYB proteins were classified
into three groups (I-III) based on phylogeny. Sequence and domain analysis
revealed presence of two conserved DNA binding MYB domains in the selected MYB
proteins. Promoter analysis indicated presence of cis-regulatory elements related
to light signaling, development, and stress response. Expression analysis of
selected Arabidopsis MYB genes revealed their function in plant development and
abiotic stress response, consistent with gene ontology annotations. Together,
these results provide a useful framework for further experimental studies for the
functional characterization of the target MYB genes in the context of regulation
of phenylpropanoid biosynthesis and plant stress response.
PMID- 28490276
TI - Endometrial Stromal and Epithelial Cells Exhibit Unique Aberrant Molecular
Defects in Patients With Endometriosis.
AB - CONTEXT: Endometriosis is a chronic inflammatory disease that causes pain and
infertility in women of reproductive age. OBJECTIVE: To investigate the
pathologic pathways in endometrial stromal and epithelial cells that contribute
to the manifestation of endometriosis. DESIGN: In vitro cellular and molecular
analyses of isolated eutopic endometrial stromal and epithelial cells. METHODS:
Eutopic stromal and epithelial cells from endometriotic and normal patients were
isolated by fluorescence-activated cell sorting for paired sibling RNA sequencing
and microRNA microarray. Aberrant pathways were identified using ingenuity
pathway analysis networks and confirmed with in vitro modulation of the affected
pathways in stromal and epithelial cell cultures. RESULTS: Both stromal versus
epithelial cell types and paired endometriotic versus normal samples exhibited
distinct hierarchical clustering. Compared to normal samples, there were 151 and
215 differentially expressed genes in the endometriotic stromal and epithelial
populations, respectively, and concomitantly 9 and 16 differentially expressed
microRNAs. Overall, endometriotic stromal and epithelial cells revealed distinct
defects. In endometriotic stromal cells, key decidualization genes Zinc finger E
box Binding protein 1 (ZEB1), Heart And Neural crest Derivatives expressed 2
(HAND2), WNT4, and Interleukin 15 (IL-15) were found to be downregulated and
Periostin (POSTN) and Matrix Metallopeptidase 7 (MMP7) were upregulated.
Specifically, ZEB1 was downregulated in stromal cells by aberrant elevation in
miR-200b. In contrast, ZEB1 was found to be upregulated in endometriotic
epithelial cells through associated upregulation of transforming growth factor
beta1 (TGFbeta1), inducer of the TGFbeta1-Bone Morphogenetic Protein 2 (BMP2)
MMP2-Prostaglandin-endoperoxide Synthase 2 (COX2)-ZEB1 pathway, which activates
epithelial-mesenchymal transition. CONCLUSION: Manifestation of endometriosis
involves dysregulation of unique molecular pathways within the diseased
endometrial stromal and epithelial cells in the endometrium. Targeting the cell
type-specific defects may offer a novel approach to treating endometriosis.
PMID- 28490277
TI - Interleukin-33 Promotes Recruitment of Microglia/Macrophages in Response to
Traumatic Brain Injury.
AB - Traumatic brain injury (TBI) is a devastating condition, often leading to life
long consequences for patients. Even though modern neurointensive care has
improved functional and cognitive outcomes, efficient pharmacological therapies
are still lacking. Targeting peripherally derived, or resident inflammatory,
cells that are rapid responders to brain injury is promising, but complex, given
that the contribution of inflammation to exacerbation versus improved recovery
varies with time post-injury. The injury-induced inflammatory response is
triggered by release of alarmins, and in the present study we asked whether
interleukin-33 (IL-33), an injury-associated nuclear alarmin, is involved in TBI.
Here, we used samples from human TBI microdialysate, tissue sections from human
TBI, and mouse models of central nervous system injury and found that expression
of IL-33 in the brain was elevated from nondetectable levels, reaching a maximum
after 72 h in both human samples and mouse models. Astrocytes and
oligodendrocytes were the main producers of IL-33. Post-TBI, brains of mice
deficient in the IL-33 receptor, ST2, contained fewer microglia/macrophages in
the injured region than wild-type mice and had an altered cytokine/chemokine
profile in response to injury. These observations indicate that IL-33 plays a
role in neuroinflammation with microglia/macrophages being cellular targets for
this interleukin post-TBI.
PMID- 28490278
TI - The Perceived Experience of Children Bereaved by Parental Suicide.
AB - Children whose parent died by suicide are a vulnerable and underserved
population. This phenomenon will be described, as well as implications for
practice and research. "Double Whammy," a conceptualization of the overall
experience of this marginalized group, emerged through two in-depth interviews
from a phenomenological qualitative study with professionals who facilitate
support groups for children bereaved by parental suicide. It was corroborated
with current literature and practice experiences of the authors and their
colleagues. Stigma was the largest contributor to the "Double Whammy," and the
following themes emerged as well: feeling isolated, feeling abandoned, and
feeling responsible. The self-volition of suicide challenges how bereaved
children make meaning and internalize feelings about the deceased parent, one's
self, and others. Developmentally appropriate education about suicide grief,
depression, and normalizing the grief process is pivotal in helping children to
effectively cope and manage their feelings.
PMID- 28490281
TI - Beyond Recovery.
AB - It is a worldwide trend that more households are having pets or companion
animals. Hence, there has been an increasing number of animal lovers experience
companion animal loss bereavement. This form of bereavement has not been explored
in Chinese societies. We conducted a qualitative study using in-depth interviews
with 31 animal lovers and recruited through convenience and snowball sampling in
Hong Kong. Companion animal loss bereavement appears to share similar features to
other forms of bereavement but also has its unique features. The intensity of
grief seemed to be affected by factors like the strength of the human-animal
bond, lack of empathy from closed ones, being married without children, and
euthanasia decision. Although the bereavement was distressful for many of our
participants, many of them gradually achieved personal growth from their loss
experience. We have identified seven common themes from the interview data and
through self-reliance, social-supported, or professional-supported coping
behaviors, people bereaved by animal loss can achieve growth from their
experience. This study shows that postbereavement growth is possible from pet
loss bereavement when appropriate coping strategies are adopted by the bereaved
but some professional help may be needed.
PMID- 28490282
TI - Death Cafe.
AB - This article explains the meaning of the phrase Death Cafe and describes what
typically occurs at a Death Cafe gathering. The article traces the history of the
Death Cafe movement, explores some reasons why people take part in a Death Cafe
gathering, and gives examples of what individuals think they might derive from
their participation. In addition, this article notes similarities between the
Death Cafe movement and three other developments in the field of death, dying,
and bereavement. Finally, this article identifies two provisional lessons that
can be drawn from Death Cafe gatherings and the Death Cafe movement itself.
PMID- 28490283
TI - Companion Animal Death.
AB - Human-animal relationships are increasingly incorporated into families as a
normal part of family life. Despite this, relationships with animals are often
viewed as inferior to human relationships. This becomes problematic during times
of loss and grief when members of a grieving companion animal owner's support
system do not understand the salience of the relationship with the animal.
Veterinary and other helping professionals need basic information about the
experience of companion animal loss in order to help support and normalize the
experiences of grieving companion animal owners. The present study qualitatively
describes human-animal relationships and the subsequent loss and coping
experienced by owners of beloved companion animals. Comparison with human and
other types of loss and factors unique to companion animal loss are discussed,
and practical applications for veterinary and other helping professionals are
provided.
PMID- 28490284
TI - The Bereavement Guilt Scale.
AB - The rationale, development, and validation of the Bereavement Guilt Scale (BGS)
are described in this article. The BGS was based on a theoretically developed,
multidimensional conceptualization of guilt. Part 1 describes the generation of
the item pool, derived from in-depth interviews, and review of the scientific
literature. Part 2 details statistical analyses for further item selection
(Sample 1, N = 273). Part 3 covers the psychometric properties of the emergent
BGS (Sample 2, N = 600, and Sample 3, N = 479). Confirmatory factor analysis
indicated that a five-factor model fit the data best. Correlations of BGS scores
with depression, anxiety, self-esteem, self-forgiveness, and mode of death were
consistent with theoretical predictions, supporting the construct validity of the
measure. The internal consistency and test-retest reliability were also
supported. Thus, initial testing or examination suggests that the BGS is a valid
tool to assess multiple components of bereavement guilt. Further psychometric
testing across cultures is recommended.
PMID- 28490285
TI - A comparative study of short-term outcomes of colorectal cancer surgery in the
elderly population.
AB - BACKGROUND: Colorectal Cancer (CRC) is a disease of the elderly, and with an
ageing population, oncological surgical procedures for CRC in the elderly is
expected to increase. However, the balance between surgical benefits and risks
associated with age and comorbidities in elderly patients is obscure. MATERIALS
AND METHODS: A retrospective database of consecutive patients who received CRC
surgery was used to compare short-term surgical and oncological outcomes between
patients aged >=75 and <75 years old undergoing CRC resection. RESULTS: There
were 54 patients (63.5%) in the <75 group and 31 patients (36.5%) in the >=75
group. Overall, there were no differences between the <75 and >=75 groups in
postoperative HDU/ITU stay, median hospital LOS or 30-day mortality rates.
Patients >=75 had a higher preoperative performance status (25.9% versus 71.0%, p
< .001), but no difference in ASA Grade and referral pattern, proportion of
emergency operations, cancer staging, resection margins, achievement of curative
resection or median lymph node yield. There was a significantly higher use of
adjuvant chemotherapy in the <75 age group (48.1% versus 25.8%, p = .043).
CONCLUSIONS: With adequate patient selection, CRC resection in elderly patients
is not associated with higher postoperative mortality or worse short-term
oncological benefits.
PMID- 28490286
TI - Loss of consciousness, collapse and associated driving restrictions: a
retrospective case note review - an important reminder regarding driving
restrictions.
AB - Background and aims National guidelines outlining medical standards for fitness
to drive are provided by The Driver and Vehicle Licensing Agency. We aimed to
establish whether patients presenting with collapse or loss of consciousness
received documented advice regarding driving restrictions, if appropriate for
their working diagnosis. Methods and results A retrospective case note review was
undertaken over a four-month period for emergency patients clinically coded as
seizure/convulsion (R568) and collapse/syncope (R55X); 163 patients had a primary
or working diagnosis on discharge that suggested driving status and restrictions
could have been reviewed. Six groupings of diagnoses were noted, and variation
was seen amongst documentation for each. Current driving status was documented
for 32 patients, and 34 had restriction advice documented; 73% (119 patients) had
further investigations or clinic review planned. Conclusion Documentation of
driving status and restrictions is poor. This audit serves to remind clinicians
of the importance of considering driving status when discharging patients who
have presented with collapse or loss of consciousness. Recent high-profile media
coverage regarding medical driving restrictions, both locally and nationally,
have emphasised the need for knowledge of The Driver and Vehicle Licensing Agency
guidance.
PMID- 28490287
TI - Cheiro-oral syndrome.
AB - We describe a 64-year-old man who presented to the emergency department with a
two-day history of left perioral and hand numbness. Examination revealed impaired
sensation of the left corner of the mouth and ipsilateral fingers. Neuroimaging
showed an acute right thalamic lacunar infarct consistent with the diagnosis of
cheiro-oral syndrome. In this report, we discuss the importance of recognising
this syndrome and instituting appropriate management to prevent further
cerebrovascular events.
PMID- 28490288
TI - Reference Values of Static Balance in Spanish Preschool Children.
AB - The purpose of this study was to examine age and sex differences in static
balance (SB) and to determine norm-referenced values for Spanish preschool
children. A total of 3,575 children, aged 3-6 years (age = 56.08 +/- 11.11
months; body mass index = 15.94 +/- 1.91 kg/m2; 1,759 girls and 1,816 boys) were
selected from 51 schools in southern Spain. To measure SB, we used the Stork
Balance Stand Test, averaging both right and left foot data for determining SB
normative values, expressed in percentiles. Girls exhibited a better performance
than boys at four years of age ( p = .010, Cohen's d = -0.165), but a poorer
performance at six years ( p = .002, Cohen's d = 0.247). SB performance of the
entire sample was higher with increased age, except for 5-6 years.
PMID- 28490289
TI - Combating mutations in genetic disease and drug resistance: understanding
molecular mechanisms to guide drug design.
AB - INTRODUCTION: Mutations introduce diversity into genomes, leading to selective
changes and driving evolution. These changes have contributed to the emergence of
many of the current major health concerns of the 21st century, from the
development of genetic diseases and cancers to the rise and spread of drug
resistance. The experimental systematic testing of all mutations in a system of
interest is impractical and not cost-effective, which has created interest in the
development of computational tools to understand the molecular consequences of
mutations to aid and guide rational experimentation. Areas covered: Here, the
authors discuss the recent development of computational methods to understand the
effects of coding mutations to protein function and interactions, particularly in
the context of the 3D structure of the protein. Expert opinion: While significant
progress has been made in terms of innovative tools to understand and quantify
the different range of effects in which a mutation or a set of mutations can give
rise to a phenotype, a great gap still exists when integrating these predictions
and drawing causality conclusions linking variants. This often requires a
detailed understanding of the system being perturbed. However, as part of the
drug development process it can be used preemptively in a similar fashion to
pharmacokinetics predictions, to guide development of therapeutics to help guide
the design and analysis of clinical trials, patient treatment and public health
policy strategies.
PMID- 28490290
TI - High confidence in falsely recognizing prototypical faces.
AB - We applied a metacognitive approach to investigate confidence in recognition of
prototypical faces. Participants were presented with sets of faces constructed
digitally as deviations from prototype/base faces. Participants were then tested
with a simple recognition task (Experiment 1) or a multiple-choice task
(Experiment 2) for old and new items plus new prototypes, and they showed a high
rate of confident false alarms to the prototypes. Confidence and accuracy
relationship in this face recognition paradigm was found to be positive for
standard items but negative for the prototypes; thus, it was contingent on the
nature of the items used. The data have implications for lineups that employ
match-to-suspect strategies.
PMID- 28490291
TI - Australia's Health Care Homes: laying the right foundations.
PMID- 28490294
TI - Failing to plan is planning to fail: advance care directives and the Aboriginal
people of the Top End.
PMID- 28490292
TI - Countering cognitive biases in minimising low value care.
AB - Cognitive biases in decision making may make it difficult for clinicians to
reconcile evidence of overuse with highly ingrained prior beliefs and intuition.
Such biases can predispose clinicians towards low value care and may limit the
impact of recently launched campaigns aimed at reducing such care. Commonly
encountered biases comprise commission bias, illusion of control, impact bias,
availability bias, ambiguity bias, extrapolation bias, endowment effects, sunken
cost bias and groupthink. Various strategies may be used to counter such biases,
including cognitive huddles, narratives of patient harm, value considerations in
clinical assessments, defining acceptable levels of risk of adverse outcomes,
substitution, reflective practice and role modelling, normalisation of deviance,
nudge techniques and shared decision making. These debiasing strategies have
considerable face validity and, for some, effectiveness in reducing low value
care has been shown in randomised trials.
PMID- 28490295
TI - Changes in medical education to help physicians meet future health care needs.
PMID- 28490296
TI - No Jab, No Pay and vaccine refusal in Australia: the jury is out.
PMID- 28490297
TI - A blinding eye injury caused by chasing Pokemon.
PMID- 28490298
TI - Raccoon eyes in systemic light chain amyloidosis.
PMID- 28490299
TI - Complicated silicosis resulting from occupational exposure to engineered stone
products.
PMID- 28490300
TI - The scratch test for determining the inferior hepatic margin.
PMID- 28490301
TI - Coronary occlusion, denial and dissociation.
PMID- 28490302
TI - Reducing the incidence of burn injuries to Indigenous Australian children.
PMID- 28490303
TI - The frequency of eye examinations in people with diabetes.
PMID- 28490304
TI - Indigenous and non-Indigenous Australian children hospitalised for burn injuries:
a population data linkage study.
AB - OBJECTIVE: To investigate differences in the characteristics of burn injuries
leading to hospitalisation of Indigenous Australian and non-Indigenous children
in New South Wales.Design, setting: Population-based cohort analysis of linked
hospital and mortality data for 2000-2014. PARTICIPANTS: 35 749 Indigenous and 1
088 938 non-Indigenous children aged 0-13 years. MAIN OUTCOME MEASURES: The
external cause of the injury, its anatomic location, total body surface area
affected (%TBSA), burn depth, length of hospital stay (LOS). RESULTS: 4246 non
Indigenous and 323 Indigenous children were hospitalised for a first burn injury
during 2000-2014. A higher proportion of Indigenous than non-Indigenous children
were admitted with burns affecting more than 10% TBSA (17% v 12%) and a lower
proportion of Indigenous children than of non-Indigenous children were treated at
a hospital with a paediatric tertiary referral burn unit (40% v 50%; P < 0.001).
The mean LOS during the index admission was almost 3 days longer for Indigenous
children than for non-Indigenous children (6.1 days [95% CI, 4.8-7.4 days] v 3.4
days [95% CI, 3.2-3.7 days]; P < 0.001); the difference in LOS was still
statistically significant after adjusting for characteristics of the burn and
residential location. CONCLUSION: The proportion of Indigenous children with
burns who presented with burn injuries affecting more than 10% TBSA was greater
than for non-Indigenous children. Their mean LOS was also longer; the difference
remained statistically significant after adjusting for characteristics of the
burn and of residential location.
PMID- 28490305
TI - Long term risk of severe retinopathy in childhood-onset type 1 diabetes: a data
linkage study.
AB - OBJECTIVES: To determine the relationship between glycaemic control trajectory
and the long term risk of severe complications in people with type 1 diabetes
mellitus, as well as the effects of paediatric and adult HbA1c levels. DESIGN,
SETTING, PARTICIPANTS: Data linkage study of data for adults with childhood-onset
type 1 diabetes (diagnosed during 1975-2010) who had transitioned from paediatric
diabetes care at the Royal Children's Hospital (Melbourne) to adult diabetes care
at the Royal Melbourne Hospital during 1992-2013. MAIN OUTCOME MEASURES: Severe
complications were categorised as severe diabetic retinopathy (SDR), chronic
kidney disease, ulceration or amputation, and death. Mean HbA1c levels were
calculated for the paediatric and adult periods. Four glycaemic control
trajectories were defined according to mean paediatric and adult HbA1c levels:
stable low (paediatric and adult HbA1c <= 66 mmol/mol); improving (paediatric
HbA1c > 66 mmol/mol, adult HbA1c <= 66 mmol/mol); worsening (paediatric HbA1c <=
66 mmol/mol, adult HbA1c > 66 mmol/mol); and stable high (paediatric and adult
HbA1c > 66 mmol/mol). RESULTS: 503 eligible participants (253 men) were
identified, 26 (5.2%) of whom had at least one severe complication, including 16
with SDR (3.2%). No-one in the stable low group, but 4% of the improving, 1% of
the worsening, and 7% of the stable high groups developed SDR. Higher mean
paediatric (per 10.9 mmol/mol increase: odds ratio [OR], 2.9; 95% CI, 1.9-4.3; P
< 0.01) or adult HbA1c levels (OR, 2.1; 95% CI, 1.4-3.1; P < 0.01) were
associated with increased risk of SDR, as was longer duration of type 1 diabetes
(per additional year: OR, 1.3; 95% CI, 1.2-1.5; P < 0.01). CONCLUSION: SDR was
associated with higher paediatric HbA1c levels, independent of glycaemic control
during adulthood; it was not documented in patients with a stable low glycaemic
control trajectory.
PMID- 28490306
TI - Adherence to diabetic eye examination guidelines in Australia: the National Eye
Health Survey.
AB - OBJECTIVE: To determine adherence to NHMRC eye examination guidelines for
Indigenous and non-Indigenous Australian people with diabetes. DESIGN: Cross
sectional survey using multistage, random cluster sampling. SETTING: Thirty
randomly selected geographic sites in the five mainland Australian states and the
Northern Territory, stratified by remoteness. PARTICIPANTS: 1738 Indigenous
Australians aged 40-92 years and 3098 non-Indigenous Australians aged 50-98 years
were recruited and examined between March 2015 and April 2016 according to a
standardised protocol that included a questionnaire (administered by an
interviewer) and a series of standard eye tests. MAIN OUTCOME MEASURES: Adherence
rates to NHMRC eye examination guidelines; factors influencing adherence.
RESULTS: Adherence to screening recommendations was significantly greater among
non-Indigenous Australians (biennial screening; 77.5%) than Indigenous
Australians (annual screening; 52.7%; P < 0.001). Greater adherence by non
Indigenous Australians was associated with longer duration of diabetes (adjusted
odds ratio [aOR], 1.19 per 5 years; P = 0.018), while increasing age was
associated with poorer adherence in non-Indigenous Australians (aOR, 0.70 per
decade; P = 0.011). For Indigenous Australians, residing in inner regional areas
(aOR, 1.66; P = 0.007) and being male (aOR, 1.46; P = 0.018) were significant
factors positively associated with adherence. CONCLUSIONS: More than three
quarters of non-Indigenous Australians with diabetes and more than half of
Indigenous Australians with diabetes adhere to the NHMRC eye examination
guidelines. The discrepancy between the adherence rates may point to gaps in the
provision or uptake of screening services in Indigenous communities, or a lack of
awareness of the guidelines. A carefully integrated diabetic retinopathy
screening service is needed, particularly in remote areas, to improve adherence
rates.
PMID- 28490307
TI - Should there be an MBS item number for advance care planning?
PMID- 28490308
TI - Management of adverse events related to new cancer immunotherapy (immune
checkpoint inhibitors).
PMID- 28490309
TI - The cardiovascular research crisis and what to do about it.
PMID- 28490310
TI - Coronary stent technology: a narrative review.
PMID- 28490311
TI - Coronary stent technology: a narrative review.
PMID- 28490312
TI - A positive step for pharmaceutical payment transparency.
PMID- 28490313
TI - Radial vs Femoral Approach in Acute Coronary Syndromes: A Meta- Analysis of
Randomized Trials.
AB - BACKGROUND: Substantial improvements have been achieved with percutaneous
coronary intervention (PCI) for the treatment of Acute Coronary Syndromes (ACS).
Nevertheless, bleeding still affects outcomes. The radial approach for PCI has
shown important benefits on access site complications, but is still not achieving
universal consensus as first choice in acute settings. Therefore, we performed a
comprehensive meta-analysis of randomized trials comparing radial vs femoral
approach in PCI for ACS. METHODS: The literature and main scientific session
abstracts were scanned for randomized studies comparing radial vs femoral
approach for PCI in ACS. Primary endpoint was mortality within 30-days. Secondary
endpoints were: 1) Major Adverse Cardiovascular Events (MACE), 2) major bleeding,
and, 3) vascular complications. RESULTS: We included 17 randomized trials,
enrolling 19325 patients. A total of 9635 patients were randomized to the radial
approach and 9690 to the femoral approach. The radial approach was associated
with a significant reduction in mortality (1.8 vs 2.5%, odds ratio, OR [95% CI] =
0.72 [0.59,0.88], p = 0.001, pheterogeneity = 0.31) and in major bleeding
complications compared with the femoral approach (1.5 vs 2.6%, OR [95% CI] = 0.57
[0.47, 0.71], p < 0.00001, pheterogeneity = 0.59), with similar advantages
observed for both ST-elevation myocardial infarction and non-ST segment elevation
ACS. MACE occurrence and vascular complications were also reduced with the radial
approach (OR [95% CI] = 0.82 [0.74, 0.92], p = 0.0005, and OR [95% CI] = 0.52
[0.47, 0.58], p < 0.00001, respectively). Our results were not influenced by
patient risk profile or the antithrombotic strategy applied. CONCLUSION: Our meta
analysis shows that among ACS patients undergoing PCI, the radial approach is
associated with a significant reduction in mortality, major bleeding
complications, MACE and vascular complication compared with the femoral approach.
PMID- 28490314
TI - Pain Experience in Dementia Subtypes: A Systematic Review.
AB - Recently, the number of studies focusing on pain in dementia has increased
considerably. Still, little attention has been paid to the influence of the
neuropathology of different dementia subtypes on pain experience. In 2003, a
review identified several studies that indicated a relation between dementia
subtype and pain experience. Now, ten years later, an update is warranted. We
conducted a systematic review to identify studies that assessed pain experience
and dementia subtypes by searching PubMed, Embase, PsycINFO, CINAHL, and Cochrane
Library. Inclusion criteria were: (1) major dementia subtype diagnosis i.e.
Alzheimer's dementia (AD), vascular dementia (VaD), frontotemporal dementia
(FTD), dementia with Lewy Bodies (DLB); (2) age >=60 years; and (3) pain
experience. We identified twelve studies that addressed AD, three studies VaD,
one study FTD, and no studies DLB. In AD, studies on clinical pain indicate a
reduced pain experience compared to controls, whereas experimental studies show
inconsistent findings. In VaD, clinical studies found that primary caregivers
rated pain equal to cognitively intact controls, although more painful locations
were reported. During self-report, elderly with VaD reported higher pain levels
than cognitively intact controls. In FTD, a significantly lower pain sensitivity
to experimental pain was found. Considering the limited number of studies, these
findings should be considered with caution. Existing literature provides some
evidence that dementia subtype affects pain experience. Further research is
needed to clarify the relation between dementia subtype and pain experience as it
could serve as basis for improving the assessment and management of pain in
people with dementia.
PMID- 28490315
TI - Orofacial Pain and Mastication in Dementia.
AB - Orofacial pain is a common condition in the general population. It is likely that
this is also the case in older persons with a dementia. However, the assessment
of (orofacial) pain in non-verbal individuals is hampered by the subjective
nature of pain, and their limited communicative abilities. To overcome this
drawback, several tools have been developed for the assessment of pain based on
observations of pain-specific facial activities, body movements, and
vocalizations. Unfortunately, none of the so far developed observational tools
have been designed specifically for the assessment of orofacial pain. While the
recent psychometric testing of the Orofacial MOBID Pain Scale did not yield
reliable outcomes, the subsequently developed Orofacial Pain Scale for Non-Verbal
Individuals (OPS-NVI) is currently being evaluated and shows good promise to be
reliable and valid. Besides the assessment of orofacial pain, an important
application of this instrument will be the investigation of the probable causal
association between impaired chewing and cognitive decline, in which orofacial
pain plays a mediating role by its negative influence on chewing ability. The
identification of this negative influence will urge opinion leaders and policy
makers to improve the oral health status in older persons with a dementia.
Ultimately, pain-free oral functioning may lead to a higher quality of life and
might help stabilizing or improving cognition in this frail and vulnerable
patient population.
PMID- 28490316
TI - Incidence and comparison of retrospective and prospective data on respiratory and
gastrointestinal infections in German households.
AB - BACKGROUND: Acute respiratory infections (ARI) and acute gastrointestinal
infections (AGI) are the most common childhood infections, and corresponding data
can either be collected prospectively or retrospectively. The aim of this study
was to estimate the incidence of respiratory and gastrointestinal episodes in
German households with children attending day care and to compare results of
prospective and retrospective data collection. METHODS: We conducted a 4 months
prospective cohort study in the winter period 2014/2015 and recruited parents of
children aged 0-6 years in 75 day care centers in Braunschweig, Lower Saxony,
Germany. For all household members, we collected information on episodes of ARI
and AGI. We applied prospective data collection in one study arm and
retrospective data collection with a reporting period of 2 months in the other.
Poisson regression was used to model monthly incidence rates for both study arms.
RESULTS: In total, 100 households (including 404 persons) participated in the
retrospective group and 77 households (282 persons) in the prospective group.
Incidence estimates for ARI (retrospective group: 0.52 per person month,
prospective group: 0.47) were higher than for AGI (retrospective group: 0.14,
prospective group: 0.13). The adjusted incidence estimates were similar in both
study arms for ARI (incidence rate ratio for retrospective versus prospective
data collection: 1.11 [confidence interval (CI) 95% 0.99; 1.24], p = 0.42) as
well as for AGI (1.10 [CI 95% 0.89; 1.37], p = 0.27). CONCLUSION: If there is no
need to collect biomaterials or data on severity of the diseases, incidence of
infections in the household setting over a short time period (2 months) can be
assessed retrospectively.
PMID- 28490317
TI - Measured, opportunistic, unexpected and naive quitting: a qualitative grounded
theory study of the process of quitting from the ex-smokers' perspective.
AB - BACKGROUND: To better understand the process of quitting from the ex-smokers'
perspective, and to explore the role spontaneity and planning play in quitting.
METHODS: Qualitative grounded theory study using in-depth interviews with 37
Australian adult ex-smokers (24-68 years; 15 males, 22 females) who quit smoking
in the past 6-24 months (26 quit unassisted; 11 used assistance). RESULTS: Based
on participants' accounts of quitting, we propose a typology of quitting
experiences: measured, opportunistic, unexpected and naive. Two key features
integral to participants' accounts of their quitting experiences were used as the
basis of the typology: (1) the apparent onset of quitting (gradual through to
sudden); and (2) the degree to which the smoker appeared to have prepared for
quitting (no evidence through to clear evidence of preparation). The resulting 2
* 2 matrix of quitting experiences took into consideration three additional
characteristics: (1) the presence or absence of a clearly identifiable trigger;
(2) the amount of effort (cognitive and practical) involved in quitting; and (3)
the type of cognitive process that characterised the quitting experience
(reflective; impulsive; reflective and impulsive). CONCLUSIONS: Quitting
typically included elements of spontaneity (impulsive behaviour) and preparation
(reflective behaviour), and, importantly, the investment of time and cognitive
effort by participants prior to quitting. Remarkably few participants quit
completely out-of-the-blue with little or no preparation. Findings are discussed
in relation to stages-of-change theory, catastrophe theory, and dual process
theories, focusing on how dual process theories may provide a way of
conceptualising how quitting can include elements of both spontaneity and
preparation.
PMID- 28490318
TI - Integrated mRNA and microRNA transcriptome variations in the multi-tepal mutant
provide insights into the floral patterning of the orchid Cymbidium goeringii.
AB - BACKGROUND: Cymbidium goeringii is a very famous traditional orchid plant in
China, which is well known for its spectacular and diverse flower morphology. In
particular, the multi-tepal mutants have considerable ecological and cultural
value. However, the current understanding of the molecular mechanisms of floral
patterning and multi-tepal development is limited. In this study, we performed
expression profiling of both microRNA (miRNA) and mRNA from wild-type and typical
multi-tepal-mutant flowers of C. goeringii for the first time, to identify the
genes and pathways regulating floral morphogenesis in C. goeringii. RESULTS:
Total clean reads of 98,988,774 and 100,188,534 bp were obtained from the wild
type and mutant library, respectively, and de novo assembled into 98,446
unigenes, with an average length of 989 bp. Among them, 18,489 were identified as
differentially expressed genes between the two libraries according to comparative
transcript profiling. The majority of the gene ontology terms and Kyoto
Encyclopedia of Genes and Genomes pathway enrichment responses were for membrane
building and ploidy-related processes, consistent with the excessive floral
organs and altered cell size observed in the mutant. There were 29 MADS-box
genes, as well as a large number of floral-related regulators and hormone
responsive genes, considered as candidates regulating floral patterning of C.
goeringii. Small RNA sequencing revealed 132 conserved miRNA families expressed
in flowers of C. goeringii, and 11 miRNAs corresponding to 455 putative target
genes were considered to be responsible for multi-tepal development. Importantly,
integrated analysis of mRNA and miRNA sequencing data showed two transcription
factor/microRNA-based genetic pathways contributing to the multi-tepal trait:
well-known floral-related miR156/SPL and miR167/ARF regulatory modes involved in
reproductive organ development; and the miR319/TCP4-miR396/GRF regulatory cascade
probably regulating cell proliferation of the multi-tepal development.
CONCLUSIONS: Integrated mRNA and miRNA profiling data provided comprehensive gene
expression information on the wild-type and multi-tepal mutant at the
transcriptional level that could facilitate our understanding of the molecular
mechanisms of floral patterning of C. goeringii. These data could also be used as
an important resource for investigating the genetics of floral morphogenesis and
various biological mechanisms of orchid plants.
PMID- 28490319
TI - Prediction of gene expression with cis-SNPs using mixed models and regularization
methods.
AB - BACKGROUND: It has been shown that gene expression in human tissues is heritable,
thus predicting gene expression using only SNPs becomes possible. The prediction
of gene expression can offer important implications on the genetic architecture
of individual functional associated SNPs and further interpretations of the
molecular basis underlying human diseases. METHODS: We compared three types of
methods for predicting gene expression using only cis-SNPs, including the
polygenic model, i.e. linear mixed model (LMM), two sparse models, i.e. Lasso and
elastic net (ENET), and the hybrid of LMM and sparse model, i.e. Bayesian sparse
linear mixed model (BSLMM). The three kinds of prediction methods have very
different assumptions of underlying genetic architectures. These methods were
evaluated using simulations under various scenarios, and were applied to the
Geuvadis gene expression data. RESULTS: The simulations showed that these four
prediction methods (i.e. Lasso, ENET, LMM and BSLMM) behaved best when their
respective modeling assumptions were satisfied, but BSLMM had a robust
performance across a range of scenarios. According to R 2 of these models in the
Geuvadis data, the four methods performed quite similarly. We did not observe any
clustering or enrichment of predictive genes (defined as genes with R 2 >= 0.05)
across the chromosomes, and also did not see there was any clear relationship
between the proportion of the predictive genes and the proportion of genes in
each chromosome. However, an interesting finding in the Geuvadis data was that
highly predictive genes (e.g. R 2 >= 0.30) may have sparse genetic architectures
since Lasso, ENET and BSLMM outperformed LMM for these genes; and this
observation was validated in another gene expression data. We further showed that
the predictive genes were enriched in approximately independent LD blocks.
CONCLUSIONS: Gene expression can be predicted with only cis-SNPs using well
developed prediction models and these predictive genes were enriched in some
approximately independent LD blocks. The prediction of gene expression can shed
some light on the functional interpretation for identified SNPs in GWASs.
PMID- 28490320
TI - Astaxanthin protects astrocytes against trauma-induced apoptosis through
inhibition of NKCC1 expression via the NF-kappaB signaling pathway.
AB - BACKGROUND: Astaxanthin (ATX) is a carotenoid pigment with pleiotropic
pharmacological properties that is seen as a possible drug for treating cerebral
ischemic injury and subarachnoid hemorrhage. Na+-K+-2Cl- co-transporter-1
(NKCC1), an intrinsic membrane protein expressed by many cell types, is activated
by various insults, leading to the formation of cell swelling and brain edema. We
previously established that ATX attenuated brain edema and improved neurological
outcomes by modulating NKCC1 expression after traumatic brain injury in mice.
This paper explored the molecular mechanism of ATX-mediated inhibition of NKCC1
utilizing an in vitro astrocyte stretch injury model. RESULTS: Stretch injury in
cultured astrocytes lowered cell viability time-dependently, which was
substantially reducing by pretreating with ATX (50 MUmol/L). Stretch injury
increased Bax level and cleaved caspase-3 activity, and decreased Bcl-2 level and
pro-caspase 3 activity, resulting in the apoptosis of astrocytes. Additionally,
stretch injury substantially raised the gene and protein expressions of
interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha and prompted
the expression and nuclear translocation of NF-kappaB. Pretreatment with ATX
remarkably prevented the trauma-induced initiation of NF-kappaB, expressions of
pro-inflammatory cytokines, and cell apoptosis. Moreover, stretch injury markedly
elevated the gene and protein expression of NKCC1, which was partly blocked by co
treatment with ATX (50 umol/L) or an NF-kappaB inhibitor (PDTC, 10 umol/L).
Cleaved caspase-3 activity was partially reduced by PDTC (10 umol/L) or an NKCC1
inhibitor (bumetanide, 50 umol/L). CONCLUSIONS: ATX attenuates apoptosis after
stretch injury in cultured astrocytes by inhibiting NKCC1 expression, and it acts
by reducing the expression of NF-kappaB-mediated pro-inflammatory factors.
PMID- 28490321
TI - Transabdominal Preperitoneal (TAPP) versus Lichtenstein operation for primary
inguinal hernia repair - A systematic review and meta-analysis of randomized
controlled trials.
AB - BACKGROUND: Transabdominal Preperitoneal (TAPP) and Lichtenstein operation are
established methods for inguinal hernia repair in clinical practice. Meta
analyses of randomized controlled studies, comparing those two methods for repair
of primary inguinal hernia, are still missing. In this study, a systematic review
and meta-analysis of published randomized controlled trials was performed to
compare early and long term outcomes of the two methods. METHODS: A literature
search was carried out to identify randomized controlled trials, which compared
TAPP and Lichtenstein repair for primary inguinal hernia. Outcome measures
included duration of operation, length of hospital stay, acute postoperative and
chronic pain, time to return to work, hematoma, wound infection, neuralgia,
numbness, scrotal swelling, seroma and hernia recurrence. A quantitative meta
analysis was performed, using Odds Ratios (OR) or Standardized Mean Difference
(SMD), and Confidence Interval (CI). RESULTS: Eight controlled randomized studies
were identified suitable for the analysis. The mean duration of the operation was
shorter in Lichtenstein repair (SMD = 6.79 min, 95% CI, -0.68 - 14.25), without
significant difference. Comparing both techniques, patients of the laparoscopic
group showed postoperatively significantly less chronic inguinal pain (OR = 0.42;
95% CI, 0.23-0.78). Analyses of the remaining outcome measures did not show any
significant differences between the two techniques. CONCLUSION: The results of
this analysis indicate that complication rate and outcome of both procedures are
comparable. TAPP operation demonstrated only one advantage over Lichtenstein
operation with significantly less chronic inguinal pain postoperatively.
PMID- 28490322
TI - The effects of video game therapy on balance and attention in chronic ambulatory
traumatic brain injury: an exploratory study.
AB - BACKGROUND: Patients with traumatic brain injury often have balance and attentive
disorders. Video game therapy (VGT) has been proposed as a new intervention to
improve mobility and attention through a reward-learning approach. In this pilot
randomized, controlled trial, we tested the effects of VGT, compared with a
balance platform therapy (BPT), on balance, mobility and selective attention in
chronic traumatic brain injury patients. METHODS: We enrolled chronic traumatic
brain injury patients (n = 21) that randomly received VGT or BPT for 3 sessions
per week for 6 weeks. The clinical outcome measures included: i) the Community
Balance & Mobility Scale (CB&M); ii) the Unified Balance Scale (UBS); iii) the
Timed Up and Go test (TUG); iv) static balance and v) selective visual attention
evaluation (Go/Nogo task). RESULTS: Both groups improved in CB&M scores, but only
the VGT group increased on the UBS and TUG with a between-group significance (p <
0.05). Selective attention improved significantly in the VGT group (p < 0.01).
CONCLUSIONS: Video game therapy is an option for the management of chronic
traumatic brain injury patients to ameliorate balance and attention deficits.
TRIAL REGISTRATION: NCT01883830 , April 5 2013.
PMID- 28490323
TI - Lifetime prevalence of mental disorders among first and second generation
individuals with Turkish migration backgrounds in Germany.
AB - BACKGROUND: This paper focuses on the lifetime prevalence of mental disorders in
individuals with Turkish migration backgrounds in Germany, as there is a lack of
reliable epidemiological data on this subject. METHODS: In total, 662 adults with
Turkish migration backgrounds were interviewed in Hamburg and Berlin by trained,
bilingual interviewers using the computerized Composite International Diagnostic
Interview (CIDI DIA-X Version 2.8) to assess diagnoses according to the DSM-IVTR.
RESULTS: The analyses showed a weighted lifetime prevalence of 78.8% for any
mental disorder, 21.6% for more than one and 7.3% for five or more disorders. Any
mood disorder (41.9%), any anxiety disorder (35.7%) and any somatoform
disorder/syndrome (33.7%) had the highest prevalences. Despite the
sociodemographic differences between the first and second generations, there were
no significant differences in the lifetime prevalence between generations, with
the exception of any bipolar disorder. Female gender, older age and no current
partnership were significantly associated with the occurrence of any mood
disorder. CONCLUSIONS: Overall, the results indicate a high lifetime prevalence
in individuals with Turkish migration backgrounds in Germany. These initial data
are highly relevant to the German clinical and psychosocial healthcare system;
however, the methodological limitations and potential biases should be considered
when interpreting the results.
PMID- 28490324
TI - The experiences of attempt survivor families and how they cope after a suicide
attempt in Ghana: a qualitative study.
AB - BACKGROUND: Ghana's socio-cultural landscape proscribes suicidal behaviour, and
this has serious ramifications for attempt survivors and their families. The
objective of this qualitative study was to understand the experiences of the
families of attempt survivors and how they cope with the aftermath of the
attempt. METHODS: Ten families with attempted suicides agreed to participate in
the study, hence they were interviewed. The information gathered was manually
analyzed according to Interpretative Phenomenological Analysis (IPA) resulting in
three major thematic areas. RESULTS: Three major themes emerged two of which
addressed negative experiences and reactions towards the attempts: Experiencing
shame and stigma, and Reactive affect. The third theme addressed the coping
resources of these informants under the theme: Surviving the stress of attempt.
The specific coping resources included personalized spiritual coping, social
support, and avoidance. CONCLUSIONS: Family systems theory is used to explain
some of the findings of this study, and the implication for clinical practice and
designing postvention programs for families after a suicide attempt are
addressed.
PMID- 28490325
TI - Reaching beyond the review of research evidence: a qualitative study of decision
making during the development of clinical practice guidelines for disease
prevention in healthcare.
AB - BACKGROUND: The judgment and decision making process during guideline development
is central for producing high-quality clinical practice guidelines, but the topic
is relatively underexplored in the guideline research literature. We have studied
the development process of national guidelines with a disease-prevention scope
produced by the National board of Health and Welfare (NBHW) in Sweden. The NBHW
formal guideline development model states that guideline recommendations should
be based on five decision-criteria: research evidence; curative/preventive effect
size, severity of the condition; cost-effectiveness; and ethical considerations.
A group of health profession representatives (i.e. a prioritization group) was
assigned the task of ranking condition-intervention pairs for guideline
recommendations, taking into consideration the multiple decision criteria. The
aim of this study was to investigate the decision making process during the two
year development of national guidelines for methods of preventing disease.
METHODS: A qualitative inductive longitudinal case study approach was used to
investigate the decision making process. Questionnaires, non-participant
observations of nine two-day group meetings, and documents provided data for the
analysis. Conventional and summative qualitative content analysis was used to
analyse data. RESULTS: The guideline development model was modified ad-hoc as the
group encountered three main types of dilemmas: high quality evidence vs. low
adoptability of recommendation; insufficient evidence vs. high urgency to act;
and incoherence in assessment and prioritization within and between four
different lifestyle areas. The formal guideline development model guided the
decision-criteria used, but three new or revised criteria were added by the
group: 'clinical knowledge and experience', 'potential guideline consequences'
and 'needs of vulnerable groups'. The frequency of the use of various criteria in
discussions varied over time. Gender, professional status, and interpersonal
skills were perceived to affect individuals' relative influence on group
discussions. CONCLUSIONS: The study shows that guideline development groups make
compromises between rigour and pragmatism. The formal guideline development model
incorporated multiple aspects, but offered few details on how the different
criteria should be handled. The guideline development model devoted little
attention to the role of the decision-model and group-related factors. Guideline
development models could benefit from clarifying the role of the group-related
factors and non-research evidence, such as clinical experience and ethical
considerations, in decision-processes during guideline development.
PMID- 28490326
TI - The clinical epidemiology of fatigue in newly diagnosed heart failure.
AB - BACKGROUND: Fatigue is a common and distressing but poorly understood symptom
among patients with heart failure (HF). This study sought to evaluate the
prevalence, predictors, and prognostic value of clinically documented fatigue in
newly diagnosed HF patients from the community. METHODS: This retrospective
cohort study consisted of 12,285 newly diagnosed HF patients receiving health
care services through the Geisinger Health System, with passive data collection
through electronic medical records (EMR). Incident HF, fatigue, and other study
variables were derived from coded data within EMRs. A collection of 87 candidate
predictors were evaluated to ascertain the strongest independent predictors of
fatigue using logistic regression. Patients were followed for all-cause mortality
for an average of 4.8 years. The associations between fatigue and 6-month, 12
month, and overall mortality were evaluated via Cox proportional hazards
regression models. RESULTS: Clinically documented fatigue was found in 4827 (39%)
newly diagnosed HF patients. Depression demonstrated the strongest association
with fatigue. Fatigue was often part of a symptom cluster, as other HF symptoms
including dyspnea, chest pain, edema, syncope, and palpitations were significant
predictors of fatigue. Volume depletion, lower body mass index, and abnormal
weight loss were also strong predictors of fatigue. Fatigue was not significantly
associated with either 6-month (HR = 1.12, p = 0.16) or overall mortality (HR =
1.00, p = 0.89) in adjusted models. CONCLUSIONS: Fatigue is a commonly documented
symptom among newly diagnosed HF patients, and its origins may lie in both
psychologic and physiologic factors. Though fatigue did provide a prognostic
signal in the short-term, this was largely explained by physiologic confounders.
Proper therapeutic remediation of fatigue in HF relies on identifying underlying
factors.
PMID- 28490327
TI - The impact of income inequality and national wealth on child and adolescent
mortality in low and middle-income countries.
AB - BACKGROUND: Income inequality and national wealth are strong determinants for
health, but few studies have systematically investigated their influence on
mortality across the early life-course, particularly outside the high-income
world. METHODS: We performed cross-sectional regression analyses of the
relationship between income inequality (national Gini coefficient) and national
wealth (Gross Domestic Product (GDP) averaged over previous decade), and all
cause and grouped cause national mortality rate amongst infants, 1-4, 5-9, 10-14,
15-19 and 20-24 year olds in low and middle-income countries (LMIC) in 2012. Gini
models were adjusted for GDP. RESULTS: Data were available for 103 (79%)
countries. Gini was positively associated with increased all-cause and
communicable disease mortality in both sexes across all age groups, after
adjusting for national wealth. Gini was only positively associated with increased
injury mortality amongst infants and 20-24 year olds, and increased non
communicable disease mortality amongst 20-24 year old females. The strength of
these associations tended to increase during adolescence. Increasing GDP was
negatively associated with all-cause, communicable and non-communicable disease
mortality in males and females across all age groups. GDP was also associated
with decreased injury mortality in all age groups except 15-19 year old females,
and 15-24 year old males. GDP became a weaker predictor of mortality during
adolescence. CONCLUSION: Policies to reduce income inequality, rather than
prioritising economic growth at all costs, may be needed to improve adolescent
mortality in low and middle-income countries, a key development priority.
PMID- 28490328
TI - Process evaluation of an interorganizational cooperation initiative in vocational
rehabilitation: the Dirigo project.
AB - BACKGROUND: This study analyzes the process of establishing and developing a
cooperative vocational rehabilitation project with special focus on
organizational and professional aspects. In the project, officials from the
Swedish Social Insurance Agency and the Swedish Public Employment Service worked
cooperatively with participants on long-term sick leave, youths with disability
benefits, and people receiving social allowances. The officials used Motivational
Interviewing (MI) as a method when meeting participants, and were able to offer
flexible and tailored case management. The goal was to improve work ability and
promote self-sufficiency. METHODS: The process evaluation was carried out through
continuous data collection throughout the project (2012-2014), resulting in a
total of 28 individual interviews and 17 focus groups with officials and
managers. The material was categorized through an inductive content analysis, and
analyzed using social capital as a theoretical frame. RESULTS: The evaluation
points to how issues related to design, organization and management contributed
to the project not reaching its goals, e.g. problems with recruitment of
participants, the funding structure, and staffing problems on the managerial
level. Still, officials reported positive effects of close cooperation, which was
perceived as facilitating the case management by fostering a mutual understanding
and access to resources and rehabilitation measures from more than one authority.
CONCLUSIONS: Cooperative work combined with the use of MI and flexible case
management seem to promote an increased trust between officials from different
authorities and participants, which in the study is conceptualized as bonding and
bridging social capital (between officials) and linking social capital (between
officials and participants). The organizational problems combined with the
relatively large differences in approaches between the project and regular
practice obstructed implementation, where the authorities involved did not appear
to be ready for implementing methodologies that require organizational
restructuring.
PMID- 28490329
TI - Directed evolution and secretory expression of a pyrethroid-hydrolyzing esterase
with enhanced catalytic activity and thermostability.
AB - BACKGROUND: Pyrethroids are potentially harmful to human health and ecosystems.
It is necessary to develop some efficient strategies to degrade pyrethroid
residues. Biodegradation is generally considered as a safe, efficient, and
inexpensive way to eliminate environmental contaminants. To date, although
several pyrethroid-hydrolyzing esterases have been cloned, there has been no
report about a pyrethroid hydrolase with high hydrolytic activity, good
stability, and high productivity, indispensable enzymatic properties in practical
biodegradation. Almost all pyrethroid hydrolases are intracellular enzymes, which
require complex extraction protocols and present issues in terms of easy
inactivation and low production. RESULTS: In this study, random mutagenesis was
performed on one pyrethroid-hydrolyzing esterase, Sys410, to enhance its activity
and thermostability. Two beneficial mutations, A171V and D256N, were obtained by
random mutagenesis and gave rise to the mutant M2. The mutant displayed ~1.5-fold
improvement in the kcat/Km value and 2.46-fold higher catalytic activity. The
optimal temperature was 10 degrees C higher than that of the wild-type enzyme
(55 degrees C). The half-life at 40-65 degrees C was 3.3-310 times longer. It
was surprising that M2 has a half-life of 12 h at 70 degrees C while Sys410 was
completely inactivated at 70 degrees C. In addition, the desired gene was
extracellularly expressed in a Pichia pastoris host system. The soluble
expression level reached up to 689.7 mg/L. Remarkably, the enzyme could
efficiently degrade various pyrethroids at moderate temperature for 15 min,
exceeding a hydrolysis rate of 98%, which is the highest value ever reported.
CONCLUSIONS: This is the first report about random mutagenesis and secretory
expression of pyrethroid-hydrolyzing esterase with high-level productivity and
purity in P. pastoris. Broad substrate specificity, enhanced activity and
thermostability make M2 an ideal candidate for the biodegradation of pyrethroid
residues.
PMID- 28490330
TI - Comparative measurements of bone mineral density and bone contrast values in
canine femora using dual-energy X-ray absorptiometry and conventional digital
radiography.
AB - BACKGROUND: Aseptic loosening due to bone remodelling processes after total hip
replacement is one common cause for revision surgery. In human medicine, dual
energy X-ray absorptiometry (DEXA) is the gold standard for quantitative
evaluation of bone mineral density, whereas in veterinary medicine conventional
radiography is used for follow-up studies. Recently, a method has been described
using digital X-ray images for quantitative assessment of grey scale values of
bone contrast. Therefore, the aim of the present study was to evaluate the
correlation of bone mineral density (BMD) measured by DEXA with grey scale values
(GV) measured in digital X-ray images (RX50, RX66) ex vivo. RESULTS: The measured
GV in the chosen X-ray settings showed on average a good correlation (r = 0.61)
to the measured BMD with DEXA. Correlation between the two X-ray settings was
very good (r = 0.81). For comparisons among regions of interests (ROIs) a
difference of 8.2% was found to be statistically significant, whereas in the case
of RX50 and RX66 differences of 5.3% and 4.1% were found to be statistically
significant. CONCLUSIONS: Results indicate that measuring absolute changes in
bone mineral density might be possible using digital radiography. Not all
significant differences between ROIs detectable with DEXA can be displayed in the
X-ray images because of the lower sensitivity of the radiographs. However, direct
comparison of grey scale values of the periprosthetic femur in one individual
patient during the follow-up period, in order to predict bone remodelling
processes, should be possible, but with a lesser sensitivity than with DEXA. It
is important that the same X-ray settings are chosen for each patient for follow
up studies.
PMID- 28490331
TI - Quantifying capture stress in free ranging European roe deer (Capreolus
capreolus).
AB - BACKGROUND: To understand and reduce the concomitant effects of trapping and
handling procedures in wildlife species, it is essential to measure their
physiological impact. Here, we examined individual variation in stress levels in
non-anesthetized European roe deer (Capreolus capreolus), which were captured in
box traps and physically restrained for tagging, biometrics and bio-sampling. In
winter 2013, we collected venous blood samples from 28 individuals during 28
capture events and evaluated standard measurements for stress (heart rate, body
temperature, neutrophil to lymphocyte ratio, lactate and total cortisol).
Additionally, we assessed stress using the immunological tool, Leukocyte Coping
Capacity (LCC), a real-time proxy for stress measuring oxygen radical production
by leukocytes. Finally, the behavioral response to handling was recorded using a
scoring system. RESULTS: LCC and therefore stress levels were negatively
influenced by the time animals spent in the box trap with human presence at the
capture site prior to handling. In contrast, none of the classical stress
measures, including total cortisol, nor the behavioral assessment, were
correlated with the stressor tested (time of human presence prior to handling)
and thus did not provide a clear depiction regarding the extent of the animals
short-term stress response. CONCLUSIONS: Overall our study verifies the LCC as a
strong method to quantify short-term stress reactions in wildlife. Moreover, our
results clearly show that human presence at the trapping site prior to handling
should be kept to an absolute minimum in order to reduce stress levels.
PMID- 28490332
TI - Feasibility of the Participation and Activity Inventory for Children and Youth
(PAI-CY) and Young Adults (PAI-YA) with a visual impairment: a pilot study.
AB - BACKGROUND: Having a visual impairment affects quality of life, daily functioning
and participation. To assess rehabilitation needs of visually impaired children
and young adults, the Participation and Activity Inventory for Children and Youth
(PAI-CY) and Young Adults (PAI-YA) were developed. The PAI-CY comprises four
questionnaires for different age categories: 0-2 years, 3-6 years, 7-12 years and
13-17 years. This pilot study assesses the feasibility and acceptability of the
PAI-CY and PAI-YA, and the relevance of the content of the questionnaires.
METHODS: In addition to the regular admission procedure, the PAI-CY and PAI-YA
were completed by 30 participants (six per questionnaire). For the PAI-CY,
parents completed the questionnaire online prior to admission. From age 7 years
onwards, children completed the questionnaire face-to-face with a rehabilitation
professional during the admission procedure. Young adults completed the PAI-YA
online. Subsequently, participants and professionals administered an evaluation
form. RESULTS: Overall, 85% of the parents rated all aspects of the PAI-CY
neutral to positive, whereas 100% of all children and young adults were neutral
to positive on all aspects, except for the duration to complete. The main
criticism of professionals was that they were unable to identify actual
rehabilitation needs using the questionnaires. Minor adjustments were recommended
for the content of questions. CONCLUSIONS: Parents, children and young adults
were mostly satisfied with the questionnaires, however, professionals suggested
some changes. The adaptations made should improve satisfaction with content,
clarification of questions, and satisfaction with the questionnaires in compiling
a rehabilitation plan. Although face and content validity has been optimized, a
larger field study is taking place to further develop and evaluate the
questionnaires.
PMID- 28490333
TI - Micronutrient powders to combat anemia in young children: does it work?
AB - In developing countries, anemia and iron deficiency in early childhood are two
highly prevalent public health problems. Providing caregivers with a powder
containing multiple vitamins and minerals (also known as micronutrient powder or
MNP) as a food supplement is a widely used strategy to combat these problems.
However, concerns exist around MNP programs with regards to effectiveness and
potential negative impact on diarrheal disease prevalence and gut flora. Teshome
et al. (BMC Medicine 15:89, 2017) recently tested a MNP with a new iron
formulation, iron-EDTA, which has a potentially higher bioavailability and thus
requires a lower iron content. Nevertheless, neither the new formulation nor the
standard formulation decreased anemia prevalence as compared to a control MNP
without iron. However, in all groups, anemia prevalence was reduced after 30 days
of intervention, and iron deficiency prevalence was significantly lower in
children receiving iron-EDTA, showing that the new formulation holds promise.
More research is needed to verify whether the lower iron content of these MNPs
can also reduce the prevalence of associated side effects.Please see related
article: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0839-z
.
PMID- 28490334
TI - HN1 contributes to migration, invasion, and tumorigenesis of breast cancer by
enhancing MYC activity.
AB - BACKGROUND: Hematological and neurological expressed 1 (HN1) is upregulated in
many tumors, but the role of HN1 in breast cancer progression and its regulatory
mechanism have not been well understood. METHODS: To study the role of HN1 in the
initiation and progression of breast cancer, we examined HN1 levels in breast
cancer cells and tissues and analyzed the relationship between HN1 levels and
patient survival. We used mammosphere formation assay, side population analysis,
wound healing assay, transwell assay, soft agar formation assay, and xenografted
tumor model to determine the effect of HN1 on the expansion of breast cancer stem
cells, and the migration, invasion and tumorigenesis of breast cancer. To
determine whether HN1 regulates MYC, we used quantitative real-time PCR and
Western blot analysis to assess the expression of MYC and their targeted genes to
determine the phenotype caused by knockdown of MYC in breast cancer cell with HN1
overexpression. RESULTS: In this study, we found that HN1 was upregulated in
breast cancer tissues. Patients with high levels of HN1 expression had
significantly shorter survival than those with low HN1 expression. In breast
cancer cell line, ectopic overexpression of HN1 not only promoted the expansion
of breast cancer stem cells, but also promoted cell migration, invasion, and
tumorigenesis, while knockdown of HN1 reduced these effects. Furthermore, there
was a positive correlation between MYC (also known as c-MYC) level and HN1 level,
mechanism analysis suggested HN1 promoted the expression of MYC and its targeted
genes like CDK4, CCND1, p21, CAV1, and SFRP1. Downregulation of MYC abrogated the
effect of HN1 overexpression in breast cancer cell lines. CONCLUSION: Taken
together, these data reveal that HN1 promotes the progression of breast cancer by
upregulating MYC expression, and might be a therapeutic target for breast cancer.
PMID- 28490335
TI - ING5 suppresses breast cancer progression and is regulated by miR-24.
AB - BACKGROUND: The inhibitor of growth (ING) gene family of tumor suppressors is
involved in multiple cellular functions such as cell cycle regulation, apoptosis,
and chromatin remodeling. ING5 is a new member of the ING family whose function
and regulation remain largely unknown. METHODS: Quantitative real-time PCR and
western blot were used to examine the expression levels of ING5 in breast cancer
tissues. The miRNAs that potentially targeted ING5 were determined by
bioinformatics analysis and luciferase reporter assay. Cell viability assay,
transwell invasion and apoptosis assay were used to characterize the changes
induced by overexpressing or knocking down miR-24 or ING5. Hematoxylin and eosin
(H&E) staining and immunohistochemical staining for ING5 and Ki-67 were used for
xenograft assays in BALB/c nude mice. RESULTS: We showed that the ING5 protein
rather than the mRNA, was significantly downregulated in breast cancer tissues.
We also investigated the potential function of ING5 in breast tumorigenesis and
found that ING5 suppressed the proliferation and invasion of breast cancer cells
and promoted their apoptosis. Furthermore, we explored the molecular mechanisms
accounting for the dysregulation of ING5 in breast cancer cells and identified an
oncomiR, miR-24, as a direct upstream regulator of ING5. We revealed that miR-24
had the opposite effects to those of ING5 on breast cancer cells and could
accelerate xenografted tumor growth in vivo. CONCLUSION: Our findings uncover the
tumor-suppressive role of ING5 and the regulatory pathway of ING5 in breast
cancer and may provide insights into the molecular mechanisms of breast
carcinogenesis.
PMID- 28490336
TI - Characteristics of L-citrulline transport through blood-brain barrier in the
brain capillary endothelial cell line (TR-BBB cells).
AB - BACKGROUND: L-Citrulline is a neutral amino acid and a major precursor of L
arginine in the nitric oxide (NO) cycle. Recently it has been reported that L
citrulline prevents neuronal cell death and protects cerebrovascular injury,
therefore, L-citrulline may have a neuroprotective effect to improve
cerebrovascular dysfunction. Therefore, we aimed to clarify the brain transport
mechanism of L-citrulline through blood-brain barrier (BBB) using the
conditionally immortalized rat brain capillary endothelial cell line (TR-BBB
cells), as an in vitro model of the BBB. METHODS: The uptake study of [14C] L
citrulline, quantitative real-time polymerase chain reaction (PCR) analysis, and
rLAT1, system b0,+, and CAT1 small interfering RNA study were performed in TR-BBB
cells. RESULTS: The uptake of [14C] L-citrulline was a time-dependent, but ion
independent manner in TR-BBB cells. The transport process involved two saturable
components with a Michaelis-Menten constant of 30.9 +/- 1.0 MUM (Km1) and 1.69 +/
0.43 mM (Km2). The uptake of [14C] L-citrulline in TR-BBB cells was
significantly inhibited by neutral and cationic amino acids, but not by anionic
amino acids. In addition, [14C]L-citrulline uptake in the cells was markedly
inhibited by 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), which is the
inhibitor of the large neutral amino acid transporter 1 (LAT1), B0, B0,+ and
harmaline, the inhibitor of system b0,+. Gabapentin and L-dopa as the substrates
of LAT1 competitively inhibited the uptake of [14C] L-citrulline. IC50 values for
L-dopa, gabapentin, L-phenylalanine and L-arginine were 501 MUM, 223 MUM, 68.9
MUM and 33.4 mM, respectively. The expression of mRNA for LAT1 was predominantly
increased 187-fold in comparison with that of system b0,+ in TR-BBB cells. In the
studies of LAT1, system b0,+ and CAT1 knockdown via siRNA transfection into TR
BBB cells, the transcript level of LAT1 and [14C] L-citrulline uptake by LAT1
siRNA were significantly reduced compared with those by control siRNA in TR-BBB
cells. CONCLUSIONS: Our results suggest that transport of L-citrulline is mainly
mediated by LAT1 in TR-BBB cells. Delivery strategy for LAT1-mediated transport
and supply of L-citrulline to the brain may serve as therapeutic approaches to
improve its neuroprotective effect in patients with cerebrovascular disease.
PMID- 28490337
TI - Effect of sitagliptin on the echocardiographic parameters of left ventricular
diastolic function in patients with type 2 diabetes: a subgroup analysis of the
PROLOGUE study.
AB - BACKGROUND: Diabetes is associated closely with an increased risk of
cardiovascular events, including diastolic dysfunction and heart failure that
leads to a shortening of life expectancy. It is therefore extremely valuable to
evaluate the impact of antidiabetic agents on cardiac function. However, the
influence of dipeptidyl peptidase 4 inhibitors on cardiac function is
controversial and a major matter of clinical concern. We therefore evaluated the
effect of sitagliptin on echocardiographic parameters of diastolic function in
patients with type 2 diabetes as a sub-analysis of the PROLOGUE study. METHODS:
Patients in the PROLOGUE study were assigned randomly to either add-on
sitagliptin treatment or conventional antidiabetic treatment. Of the 463 patients
in the overall study, 115 patients (55 in the sitagliptin group and 60 in the
conventional group) who had complete echocardiographic data of the ratio of peak
early diastolic transmitral flow velocity (E) to peak early diastolic mitral
annular velocity (e') at baseline and after 12 and 24 months were included in
this study. The primary endpoint of this post hoc sub-analysis was a comparison
of the changes in the ratio of E to e' (E/e') between the two groups from
baseline to 24 months. RESULTS: The baseline-adjusted change in E/e' during 24
months was significantly lower in the sitagliptin group than in the conventional
group (-0.18 +/- 0.55 vs. 1.91 +/- 0.53, p = 0.008), irrespective of a higher
E/e' value at baseline in the sitagliptin group. In analysis of covariance,
sitagliptin treatment was significantly associated with change in E/e' over 24
months (beta = -9.959, p = 0.001), independent of other clinical variables at
baseline such as blood pressure, HbA1c, and medications for diabetes. Changes in
other clinical variables including blood pressure and glycemic parameters, and
echocardiographic parameters, such as cardiac structure and systolic function,
were comparable between the two groups. There was also no significant difference
in the serum levels of N-terminal-pro brain natriuretic peptide and high
sensitive C-reactive protein between the two groups during the study period.
CONCLUSIONS: Adding sitagliptin to conventional antidiabetic regimens in patients
with T2DM for 24 months attenuated the annual exacerbation in the
echocardiographic parameter of diastolic dysfunction (E/e') independent of other
clinical variables such as blood pressure and glycemic control. Trial
registration UMIN000004490 (University Hospital Medical Information Network
Clinical Trials). https://upload.umin.ac.jp/cgi-open
bin/ctr_e/ctr_view.cgi?recptno=R000005356 ; registered November 1, 2010.
PMID- 28490338
TI - International evaluation of the psychometrics of health-related quality of life
questionnaires for use among long-term survivors of testicular and prostate
cancer.
AB - BACKGROUND: Understanding of the physical, functional and psychosocial health
problems and needs of cancer survivors requires cross-national and cross-cultural
standardization of health-related quality of life (HRQoL) questionnaires that
capture the full range of issues relevant to cancer survivors. To our knowledge,
only one study has investigated in a comprehensive way whether a questionnaire
used to evaluate HRQoL in cancer patients under active treatment is also reliable
and valid when used among (long-term) cancer survivors. In this study we
evaluated, in an international context, the psychometrics of HRQoL questionnaires
for use among long-term, disease-free, survivors of testicular and prostate
cancer. METHODS: In this cross-sectional study, we recruited long-term survivors
of testicular and prostate cancer from Northern and Southern Europe and from the
United Kingdom who had participated in two phase III EORTC clinical trials.
Participants completed the SF-36 Health Survey, the EORTC QLQ-C30 questionnaire,
the QLQ-PR25 (for prostate cancer) or the QLQ-TC26 (for testicular cancer)
questionnaires, and the Impact of Cancer questionnaire. Testicular cancer
survivors also completed subscales from the Nordic Questionnaire for Monitoring
the Age Diverse Workforce. RESULTS: Two hundred forty-two men (66% response rate)
were recruited into the study. The average time since treatment was more than 10
years. Overall, there were few missing questionnaire data, although scales
related to sexuality, satisfaction with care and relationship concerns of men
without partners were missing in more than 10% of cases. Debriefing showed that
in general the questionnaires were accepted well. Many of the survivors scored at
the upper extremes of the questionnaires, resulting in floor and ceiling effects
in 64% of the scales. All of the questionnaires investigated met the threshold of
0.70 for group level reliability, with the exception of the QLQ-TC26 (mean
reliability .64) and the QLQ-PR25 (mean reliability .69). The questionnaires were
able to discriminate clearly between patients with and without comorbid
conditions. CONCLUSIONS: The currently available HRQoL questionnaires exhibit
acceptable psychometric properties and were well received by patients, but
additional efforts are needed to ensure that the full range of survivor-specific
issues is assessed.
PMID- 28490339
TI - Distribution and phylogeny of Wolbachia strains in wild mosquito populations in
Sri Lanka.
AB - BACKGROUND: Wolbachia are a group of maternally inherited intracellular bacteria
known to be widespread among arthropods. Infections with Wolbachia cause declines
of host populations, and also induce host resistance to a wide range of
pathogens. Over the past few decades, researchers were curious to use Wolbachia
as a biological tool to control mosquito vectors. During the present study,
assessment of the prevalence of Wolbachia infections among wild mosquito
populations in Sri Lanka where mosquito-borne diseases are a major health
concern, was carried out for the first time. DNA was extracted from the abdomens
of mosquitoes, collected from seven provinces, and screened for the presence of
Wolbachia by PCR using wsp and groE primers. Group-specific and strain-specific
primers were used to classify Wolbachia into the supergroups A and B, and into
the strains Mel, AlbA and Pip. RESULTS: A total of 330 individual mosquitoes
belonging to 22 species and 7 genera were screened. Eighty-seven mosquitoes
(26.36%) belonging to four species (i.e. Aedes albopictus, Culex
quinquefasciatus, Armigeres subalbatus and Mansonia uniformis) were positive for
Wolbachia infections. Primary vector of the dengue fever, Ae. aegypti was
negative for Wolbachia infections while the secondary vector, Ae. albopictus,
showed a very high infection rate. The filarial vector C. quinquefasciatus had a
relatively high rate of infection. Japanese encephalitis vectors C. gelidus and
C. triteaneorynchus, and the Anopheles vectors of malaria were negative for
Wolbachia infections. Nine sequences of Wolbachia-positive PCR products were
deposited in the GenBank and compared with other available data. Aedes albopictus
was infected with both Wolbachia strains A (AlbA) and B (Pip) supergroups.
Phylogenetic analysis of the wsp sequences showed two major branches confirming
identities obtained from the PCR screening with strain-specific primers.
CONCLUSION: Wolbachia infections were found only among four mosquito species in
Sri Lanka: Aedes albopictus, Culex quinquefasciatus, Armigeres subalbatus and
Mansonia uniformis. Sequence data showed high haplotype diversity among the
Wolbachia strains.
PMID- 28490340
TI - Morbidity and oncologic outcome after saphenous vein-sparing inguinal
lymphadenectomy in melanoma patients.
AB - BACKGROUND: Inguinal lymph node dissection (LND) is a surgical procedure with a
high morbidity rate. Variations in surgical procedure, such as sparing of the
saphenous vein, have been proposed to reduce surgical morbidity. While sparing of
the saphenous vein has shown promising results in earlier studies, data for this
procedure in melanoma patients are rare. In this retrospective study, we report
10-year findings on the effects of saphenous vein-sparing LND on surgical
morbidity and oncologic outcomes in melanoma patients. METHODS: A retrospective
analysis of melanoma patients receiving inguinal LND in our facility between 2003
and 2013 was performed. Patients were divided into two groups: the saphenous vein
resection group and the vein sparing group. Surgical morbidity, including wound
infection, lymphatic fistula, severe bleeding, neurological complications, and
chronic lymphedema, as well as regional recurrence-free survival were
investigated. RESULTS: A total of 106 patients were included in this study; of
these, the saphenous vein was spared in 41 patients (38.7%). The rate of
lymphatic fistula was 51.6 vs. 48.8%, wound infection occurred in 31.3 vs. 24.4%,
and patients suffered from chronic lymphedema in 30.0 vs. 26.5% in V. saphena
magna resection vs. sparing group. Differences observed, however, were not
significant. No difference in regional recurrence-free survival between the two
study groups was detected. CONCLUSIONS: The results of our retrospective analysis
could not confirm the promising results reported in earlier studies. Thus,
sparing of the saphenous vein appears to be optional.
PMID- 28490341
TI - Developmental transitions: integrating environmental cues with hormonal signaling
in the chromatin landscape in plants.
AB - Plant development is predominantly postembryonic and tuned in to respond to
environmental cues. All living plant cells can be triggered to de-differentiate,
assume different cell identities, or form a new organism. This developmental
plasticity is thought to be an adaptation to the sessile lifestyle of plants.
Recent discoveries have advanced our understanding of the orchestration of plant
developmental switches by transcriptional master regulators, chromatin state
changes, and hormone response pathways. Here, we review these recent advances
with emphasis on the earliest stages of plant development and on the switch from
pluripotency to differentiation in different plant organ systems.
PMID- 28490343
TI - Roadside opioid testing of drivers using oral fluid: the case of a country with a
zero tolerance law, Spain.
AB - BACKGROUND: Opioids can impair psychomotor performance, and driving under the
influence of opioids is associated with an increased risk of accidents. The goals
of this study were i) to determine the prevalence of opioids (heroin, morphine,
codeine, methadone and tramadol) in Spanish drivers and ii) to explore the
presence of opioids, more specifically whether they are used alone or in
combination with other drugs. METHODS: The 2008/9 DRUID database regarding Spain
was used, which provided information on 3302 drivers. All drivers included in the
study provided a saliva sample and mass-chromatographic analyses were carried out
in all cases. To determine the prevalence, the sample was weighted according to
traffic intensity. In the case of opioid use combinations, the sample was not
weighted. The detection limit for each substance was considered a positive
result. RESULTS: The prevalence of opioids in Spanish drivers was 1.8% (95% CI,
1.4-2.3). Polydrug detection was common (56.2%): of these, in two out of three
cases, two opioids were detected and cocaine was also detected in 86% of the
cases. The concentration (median [Q1-Q3] ng/ml) of the substances was low:
methadone 1.71 [0.10-15.30], codeine 40.55 [2.10-120.77], 6-acetylmorphine 5.71
[1.53-84.05], and morphine 37.40 [2.84-200.00]. Morphine was always detected with
6-acetylmorphine (heroin use). CONCLUSIONS: Driving under the influence of
opioids is relatively infrequent, but polydrug use is common. Our study shows
that 6 out of 10 drivers with methadone in their OF (likely in methadone
maintenance programs) are using other substances. This should be taken into
account by health professionals in order to properly inform patients about the
added risks of mixing substances when driving.
PMID- 28490342
TI - Rethinking alcohol interventions in health care: a thematic meeting of the
International Network on Brief Interventions for Alcohol & Other Drugs (INEBRIA).
AB - In 2016, the International Network on Brief Interventions for Alcohol & Other
Drugs convened a meeting titled "Rethinking alcohol interventions in health
care". The aims of the meeting were to synthesize recent evidence about screening
and brief intervention and to set directions for research, practice, and policy
in light of this evidence. Screening and brief intervention is efficacious in
reducing self-reported alcohol consumption for some with unhealthy alcohol use,
but there are gaps in evidence for its effectiveness. Because screening and brief
intervention is not known to be efficacious for individuals with more severe
unhealthy alcohol use, recent data showing the lack of evidence for referral to
treatment as part of screening and brief intervention are alarming. While
screening and brief intervention was designed to be a population-based approach,
its reach is limited. Implementation in real world care also remains a challenge.
This report summarizes practice, research, and policy recommendations and key
research developments from our meeting. In order to move the field forward, a
research agenda was proposed to (1) address evidence gaps in screening, brief
intervention, and referral to treatment, (2) develop innovations to address
severe unhealthy alcohol use within primary care, (3) describe the stigma of
unhealthy alcohol use, which obstructs progress in prevention and treatment, (4)
reconsider existing conceptualizations of unhealthy alcohol use that may
influence health care, and (5) identify efforts needed to improve the capacity
for addressing unhealthy alcohol consumption in all world regions.
PMID- 28490344
TI - Dosimetric advantage of volumetric modulated arc therapy in the treatment of
intraocular cancer.
AB - OBJECTIVE: The purpose of this study is to investigate the dosimetric advantages
of volumetric modulated arc therapy (VMAT) in the treatment of intraocular cancer
by comparing it directly with three-dimensional conformal radiotherapy (CRT) and
intensity-modulated radiotherapy (IMRT). METHODS: CRT plan, 7f-IMRT plan, and one
arc VMAT plan were generated for 14 intraocular cancer patients. Dosimetric and
biological quality indices for target volume and organs at risks (OARs) were
evaluated and compared. RESULTS: The target coverage presented by V95 for CRT,
IMRT and VMAT were 95.02% +/- 0.67%, 95.51% +/- 2.25%, and 95.92% +/- 3.05%,
respectively. The homogeneity index (HI) for CRT, IMRT and VMAT were 0.15 +/-
0.05, 0.23 +/- 0.05, and 0.23 +/- 0.06, respectively. IMRT and VMAT greatly
decreased the dose to ipsilateral lens compared with CRT with a D1 of 2972.66 +/-
1407.12 cGy, 3317.82 +/- 915.28 cGy and 4809.54 +/- 524.60 cGy for IMRT, VMAT and
CRT, respectively. Similar results were observed for ipsilateral eyeballs. IMRT
and VMAT also spared better on brainstem, optical nerves and optical chiasm
compared CRT. However, CRT achieved lower dose to the eyeballs compared with IMRT
and VMAT. VMAT and IMRT showed mixed results on target coverage and OAR sparing.
The average MUs and delivery time of IMRT and VMAT were 531.25 +/- 81.21 vs.
400.99 +/- 61.49 and 5.05 +/- 0.53 vs.1.71 +/- 0.69 min, respectively.
CONCLUSIONS: Although no clear distinction on PTV coverage among CRT, IMRT and
VMAT plans was observed in the treatment of intraocular cancer, VMAT and IMRT
achieved better homogeneity and conformity for target volume, and delivered fewer
doses to ipsilateral lens and eyeballs compared with CRT. However, VMAT and IMRT
increased the low dose volume to the contralateral OARs. Although VMAT and IMRT
showed mixed results on target coverage and OAR sparing, VMAT decreased MU and
delivery time significantly compared with IMRT. VMAT is a promising and feasible
external beam radiotherapy technique in the treatment of intraocular cancer
patients.
PMID- 28490345
TI - Post-2015, why delay to seek healthcare? Perceptions and field experiences from
TB healthcare providers in northern Malawi: a qualitative study.
AB - BACKGROUND: Malawi is a low-income country with high Tuberculosis (TB) burden. TB
diagnosis delay and untimely initiation of treatment is still a major problem in
Malawi which could increase the risk of tuberculosis transmission in the
communities. This study investigated factors related to the diagnostic delay of
tuberculosis from TB healthcare providers in the northern region of Malawi.
METHODS: Nine focus group discussions were conducted with 57 participants in
total. The participants were healthcare cadres including district TB officers,
clinical officers, TB nurses, laboratory technicians and Health Surveillance
Assistants (HSAs). NVivo (11.0) software was used for data analysis. RESULTS: The
factors related to diagnostic delay were categorized into three themes: client
factors, institutional factors and healthcare provider related factors. Client's
stigma and fear for HIV test, resource shortage within healthcare institutions
and the healthcare workers' poor attitude against potential patients were among
the most influential factors behind the TB diagnostic delay. CONCLUSIONS: The TB
control strategies should aim to reduce HIV stigma, improve resource supply and
improve TB healthcare workers' morale in order to achieve timely TB diagnosis.
PMID- 28490347
TI - GH-secreting pituitary macroadenoma (acromegaly) associated with progressive
dental malocclusion and refractory CPAP treatment.
AB - BACKGROUND: A link between progressive dental malocclusion, the use of a
continuous positive airway pressure mask and GH-secreting pituitary macroadenoma
(acromegaly) has not been previously reported. The present clinicopathological
analysis stresses that tooth malposition should not be seen exclusively as a
local process. CASE PRESENTATION: A 62-year-old caucasian man with no relevant
medical history reported difficulty chewing food and perceived voice alteration
during his annual periodontal check-up. He also referred stiffness of the tongue,
face, and submandibular area. The patient had been diagnosed with obstructive
sleep apnea syndrome two years previously, since when he had worn a continuous
positive airway pressure device during sleep. Exploration of the occlusion
revealed significant changes: an atypical left lateral and anterior open bite
with major buccoversion of teeth 33, 34, 35, 36. Inspection of the soft tissue
revealed only macroglossia, although external palpation indicated a subcutaneous
stiffness of the submandibular area. General analytical tests, including hormone
profiles, and magnetic resonance imaging confirmed the diagnosis of acromegaly
induced by a pituitary adenoma. Intrasellar tumor resection via transsphenoidal
approach was performed. After surgery, the patient already noted a marked
improvement of all symptoms associated with the acromegaly. Desaturation data
also evolved favourably and the pulmonologist advised the patient to abandon the
continuous positive airway pressure treatment. CONCLUSION: Progressive dental
malocclusion may be associated with a systemic disease and the use of a nasal
mask with premaxillary support may distort the diagnosis of acromegaly.
PMID- 28490346
TI - Anti-inflammatory effects of H2S during acute bacterial infection: a review.
AB - Hydrogen sulfide (H2S), previously only considered a toxic environmental air
pollutant, is now increasingly recognized as an important signaling molecule able
to modulate several cellular pathways in many human tissues. As demonstrated in
recent studies, H2S is produced endogenously in response to different cellular
stimuli and plays different roles in controlling a number of physiological
responses. The precise role of H2S in inflammation is still largely unknown. In
particular, the role of H2S in the regulation of the inflammatory response in
acute and chronic infections is being actively investigated because of its
potential therapeutic use. To study the effect of H2S as an anti-inflammatory
mediator during bacterial infections, we developed an ex vivo model of primary
cells and cell lines infected with Mycoplasma. Our data demonstrate a dichotomic
effect of H2S on the NF-kB and Nrf-2 molecular pathways, which were inhibited and
stimulated, respectively.
PMID- 28490348
TI - An international reproducibility study validating quantitative determination of
ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper(r).
AB - BACKGROUND: Accurate determination of the predictive markers human epidermal
growth factor receptor 2 (HER2/ERBB2), estrogen receptor (ER/ESR1), progesterone
receptor (PgR/PGR), and marker of proliferation Ki67 (MKI67) is indispensable for
therapeutic decision making in early breast cancer. In this multicenter
prospective study, we addressed the issue of inter- and intrasite reproducibility
using the recently developed reverse transcription-quantitative real-time
polymerase chain reaction-based MammaTyper(r) test. METHODS: Ten international
pathology institutions participated in this study and determined messenger RNA
expression levels of ERBB2, ESR1, PGR, and MKI67 in both centrally and locally
extracted RNA from formalin-fixed, paraffin-embedded breast cancer specimens with
the MammaTyper(r) test. Samples were measured repeatedly on different days within
the local laboratories, and reproducibility was assessed by means of variance
component analysis, Fleiss' kappa statistics, and interclass correlation
coefficients (ICCs). RESULTS: Total variations in measurements of centrally and
locally prepared RNA extracts were comparable; therefore, statistical analyses
were performed on the complete dataset. Intersite reproducibility showed total
SDs between 0.21 and 0.44 for the quantitative single-marker assessments,
resulting in ICC values of 0.980-0.998, demonstrating excellent agreement of
quantitative measurements. Also, the reproducibility of binary single-marker
results (positive/negative), as well as the molecular subtype agreement, was
almost perfect with kappa values ranging from 0.90 to 1.00. CONCLUSIONS: On the
basis of these data, the MammaTyper(r) has the potential to substantially improve
the current standards of breast cancer diagnostics by providing a highly precise
and reproducible quantitative assessment of the established breast cancer
biomarkers and molecular subtypes in a decentralized workup.
PMID- 28490350
TI - Efficacy of the vegetative cells of Lysinibacillus sphaericus for biological
control of insecticide-resistant Aedes aegypti.
AB - BACKGROUND: The control of Aedes aegypti is usually based on chemical
insecticides, but the overuse of these compounds has led to increased resistance.
The binary toxin produced by Lysinibacillus sphaericus in the final stages of
sporulation is used for mosquito control due to its specificity against the
culicid larvae; however, it has been proved that Ae. aegypti is refractory for
this toxin. Currently, there is no evidence of the use of L. sphaericus
vegetative cells for mosquito biocontrol. Therefore, in this study, the
vegetative cells of three L. sphaericus strains were assessed against a field
collected Ae. aegypti, resistant to temephos, and the reference Rockefeller
strain. RESULTS: Vegetative cells of L. sphaericus 2362, III(3)7 and OT4b.25
produced between 90% and 100% of larvae mortality in the reference Rockefeller
strain. Effective concentrations of each L. sphaericus strain for the four larval
stages ranged from 1.4 to 2 * 107 CFU/ml. Likewise, a consortium of L. sphaericus
assessed against a field-collected Ae. aegypti resistant to temephos and the
Rockefeller strain caused 90% of larvae mortality. Concentrations of L.
sphaericus consortium that resulted in larvae mortality of field-collected and
Rockefeller Ae. aegypti ranged from 1.7 to 2.5 * 107 CFU/ml. The vegetative cells
of L. sphaericus have no effect on the Ae. aegypti eggs and pupae. CONCLUSIONS:
The vegetative cells of L. sphaericus are effective against Ae. aegypti larvae,
meaning that it could be used in the biological control of these mosquito
species. Since the L. sphaericus consortium was effective against temephos
resistant Ae. aegypti, vegetative cells could be an alternative to overcome
insecticide-resistant populations. Further studies, should be conducted to reveal
the mode of action and the toxic principle of L. sphaericus vegetative cells.
PMID- 28490349
TI - Cognitive behavioural therapy for the management of inflammatory bowel disease
fatigue with a nested qualitative element: study protocol for a randomised
controlled trial.
AB - BACKGROUND: Fatigue is one of the most prevalent and burdensome symptoms for
patients with inflammatory bowel disease (IBD). Although fatigue increases during
periods of inflammation, for some patients it persists when disease is in
remission. Compared to other long-term conditions where fatigue has been
extensively researched, optimal management of fatigue in patients with IBD is
unknown and fatigue has rarely been the primary outcome in intervention studies.
To date, interventions for the management of IBD-fatigue are sparse, have short
term effects and have not been implemented within the existing health system.
There is a need to integrate current best evidence across different conditions,
patient experience and clinical expertise in order to develop interventions for
IBD-fatigue management that are feasible and effective. Modifying an existing
intervention for patients with multiple sclerosis, this study aims to assess the
feasibility and initial estimates of efficacy of a cognitive behavioural therapy
(CBT) intervention for the management of fatigue in patients with IBD. METHODS:
The study will be a two-arm pilot randomised controlled trial. Patients will be
recruited from one outpatient IBD clinic and randomised individually to either:
Group 1 (CBT manual for the management of fatigue, one 60-min session and seven
30-min telephone/Skype sessions with a therapist over an eight-week period); or
Group 2 (fatigue information sheet to use without therapist help). Self-reported
IBD-fatigue (Inflammatory Bowel Disease-Fatigue Scale) and IBD-quality of life
(United Kingdom Inflammatory Bowel Disease Questionnaire) and self-reported
disease activity will be collected at baseline, three, six and 12 months post
randomisation. Illness perceptions, daytime sleepiness, anxiety and depression
explanatory variables will be collected only at three months post randomisation.
Clinical and sociodemographic data will be retrieved from the patients' medical
notes. A nested qualitative study will evaluate patient and therapist experience,
and healthcare professionals' perceptions of the intervention. DISCUSSION: The
study will provide evidence of the feasibility and initial estimates of efficacy
of a CBT intervention for the management of fatigue in patients with IBD.
Quantitative and qualitative findings from the study will contribute to the
development and implementation of a large-scale randomised controlled trial
assessing the efficacy of CBT interventions for IBD-fatigue. TRIAL REGISTRATION:
ISRCTN Registry, ISRCTN17917944 . Registered on 2 September 2016.
PMID- 28490351
TI - Transcranial doppler sonography is not a valid diagnostic tool for detection of
basilar artery stenosis or in-stent restenosis: a retrospective diagnostic study.
AB - BACKGROUND: There are contradictory reports concerning the validity of
transcranial sonography (TCD and TCCS) for examinations of the basilar artery.
Here we investigated sensitivity and specificity of transcranial sonography for
the detection of basilar artery stenosis and in-stent-restenosis compared to
cerebral angiography. METHODS: We analyzed data of 104 examinations of the
basilar artery. The association between sonographic peak systolic velocity (PSV)
and degree of stenosis obtained by cerebral angiography was evaluated applying
Spearman's correlation coefficient. Receiver Operating Characteristics (ROC)
curves and areas under the curve (AUC) were calculated for the detection of a
>=50% stenosis defined by angiography. Optimal cut-off was derived using the
Youden-index. RESULTS: A weak but statistically significant correlation between
PSV and the degree of stenosis was found (n=104, rho=0.35, p<0.001). ROC analysis
for a detection of >=50% stenosis showed an AUC of 0.70, a sensitivity of 74.0%
and a specificity of 65.0% at the optimal cut off of 124 cm/s. Results were
consistent when analyzing examinations done in stented and unstented arteries
separately (TCD VS DSA/CTA in unstented artery: AUC=0.66, sensitivity 61.0%,
specificity 65.0%, TCD/TCCS VS DSA in stented artery: AUC=0.63, sensitivity
71.0%, specificity 82.0%). Comparing TCCS measurements exclusively to
angiography, ROC analysis showed an AUC of 1.00 for the detection of an in-stent
restenosis >=50% with a sensitivity and specificity of 100% when a PSV of 132
cm/s was used as a cut off value. CONCLUSION: Validity of TCD in the assessment
of basilar artery stenosis or in-stent restenosis is poor. First results for TCCS
are promising, but due to the small samplesize further studies with larger
samples sizes are warranted.
PMID- 28490352
TI - A diagnostic biomarker profile for fibromyalgia syndrome based on an NMR
metabolomics study of selected patients and controls.
AB - BACKGROUND: Fibromyalgia syndrome (FMS) is a chronic pain syndrome. A plausible
pathogenesis of the disease is uncertain and the pursuit of measurable biomarkers
for objective identification of affected individuals is a continuing endeavour in
FMS research. Our objective was to perform an explorative metabolomics study (1)
to elucidate the global urinary metabolite profile of patients suffering from
FMS, and (2) to explore the potential of this metabolite information to augment
existing medical practice in diagnosing the disease. METHODS: We selected
patients with a medical history of persistent FMS (n = 18), who described their
recent state of the disease through the Fibromyalgia Impact Questionnaire (FIQR)
and an in-house clinical questionnaire (IHCQ). Three control groups were used:
first-generation family members of the patients (n = 11), age-related individuals
without any indications of FMS or related conditions (n = 10), and healthy young
(18-22 years) individuals (n = 20). All subjects were female and the biofluid
under investigation was urine. Correlation analysis of the FIQR showed the FMS
patients represented a well-defined disease group for this metabolomics study.
Spectral analyses of urine were conducted using a 500 MHz 1H nuclear magnetic
resonance (NMR) spectrometer; data processing and analyses were performed using
Matlab, R, SPSS and SAS software. RESULTS AND DISCUSSION: Unsupervised and
supervised multivariate analyses distinguished all three control groups and the
FMS patients, and significant increases in metabolites related to the gut
microbiome (hippuric, succinic and lactic acids) were observed. We have developed
an algorithm for the diagnosis of FMS consisting of three metabolites - succinic
acid, taurine and creatine - that have a good level of diagnostic accuracy
(Receiver Operating Characteristic (ROC) analysis - area under the curve 90%) and
on the pain and fatigue symptoms for the selected FMS patient group. CONCLUSION:
Our data and comparative analyses indicated an altered metabolic profile of
patients with FMS, analytically detectable within their urine. Validation studies
may substantiate urinary metabolites to supplement information from medical
assessment, tender-point measurements and FIQR questionnaires for an improved
objective diagnosis of FMS.
PMID- 28490353
TI - Implementation of depression screening in antenatal clinics through tablet
computers: results of a feasibility study.
AB - BACKGROUND: Mobile devices may facilitate depression screening in the waiting
area of antenatal clinics. This can present implementation challenges, of which
we focused on survey layout and technology deployment. METHODS: We assessed the
feasibility of using tablet computers to administer a socio-demographic survey,
the Whooley questions and the Edinburgh Postnatal Depression Scale (EPDS) to 530
pregnant women attending National Health Service (NHS) antenatal clinics across
England. We randomised participants to one of two layout versions of these
surveys: (i) a scrolling layout where each survey was presented on a single
screen; or (ii) a paging layout where only one question appeared on the screen at
any given time. RESULTS: Overall, 85.10% of eligible pregnant women agreed to
take part. Of these, 90.95% completed the study procedures. Approximately 23% of
participants answered Yes to at least one Whooley question, and approximately 13%
of them scored 10 points of more on the EPDS. We observed no association between
survey layout and the responses given to the Whooley questions, the median EPDS
scores, the number of participants at increased risk of self-harm, and the number
of participants asking for technical assistance. However, we observed a
difference in the number of participants at each EPDS scoring interval (p =
0.008), which provide an indication of a woman's risk of depression. A scrolling
layout resulted in faster completion times (median = 4 min 46 s) than a paging
layout (median = 5 min 33 s) (p = 0.024). However, the clinical significance of
this difference (47.5 s) is yet to be determined. CONCLUSIONS: Tablet computers
can be used for depression screening in the waiting area of antenatal clinics.
This requires the careful consideration of clinical workflows, and technology
related issues such as connectivity and security. An association between survey
layout and EPDS scoring intervals needs to be explored further to determine if it
corresponds to a survey layout effect. Future research needs to evaluate the
effect of this type of antenatal depression screening on clinical outcomes and
clinic workflows. TRIAL REGISTRATION: This study was registered in
ClinicalTrials.gov under the identifier NCT02516982 on 20 July 2015.
PMID- 28490354
TI - Dual-time-point myocardial 18F-FDG imaging in the detection of coronary artery
disease.
AB - BACKGROUND: Myocardial 18F-deoxyglucose (18F-FDG) uptake has been observed to be
enhanced in patients with coronary artery disease (CAD) under fasting conditions.
However, whether the increased 18F-FDG is induced by myocardial ischemia and how
to discriminate ischemic from physiological 18F-FDG uptake have rarely been
investigated. METHODS: Under fasting conditions, 18F-FDG PET imaging was
performed in 52 patients with suspected CAD. Two 18F-FDG imaging sessions were
conducted within two hours after a single administration of 18F-FDG (dual-time
point imaging), and with an intervention of an exercise test after the first
imaging. Abnormal 18F-FDG uptake was determined by the classification of the 18F
FDG distribution pattern, and the changes of the 18F-FDG distribution between the
two PET imaging sessions were analyzed. 99mTc-sestamibi was injected at peak
exercise and myocardial perfusion imaging (MPI) was conducted after 18F-FDG
imaging. Coronary angiography was considered the reference for diagnosing CAD.
RESULTS: Overall, 54.8% (17/31) of CAD patients and 36.2% (21/58) of stenotic
coronaries showed exercise-induced abnormal uptake of 18F-FDG. Based on the
classification of the 18F-FDG distribution pattern, the sensitivity and
specificity of exercise 18F-FDG imaging to diagnose CAD was 80.6% and 95.2% by
patient analysis, 56.9% and 98.0% by vascular analysis, respectively. Compared
with MPI, 18F-FDG imaging had a tendency to have higher sensitivity (80.6% vs
64.5%, P = 0.06) on the patient level. CONCLUSION: Myocardial ischemia can induce
18F-FDG uptake. With the classification of the 18F-FDG distribution pattern, dual
time-point 18F-FDG imaging under fasting conditions is efficient in diagnosing
CAD.
PMID- 28490355
TI - Regional inequity in complete antenatal services and public emergency obstetric
care is associated with greater burden of maternal deaths: analysis from
consecutive district level facility survey of Karnataka, India.
AB - BACKGROUND: This equity focused evaluation analyses change in inter-district
inequity of maternal health services (MHS) in Karnataka state between 2006-07 &
2012-13, alongside association of MHS inequity with distribution of maternal
deaths. METHODS: Repeated cross-sectional analysis of inequity and decomposition
was done on nine district level MHS indicators using Theil's T index. Data was
obtained from population linked district level facility surveys and health
information systems. RESULTS: Inequity in births attended by skill birth
attendants decreased the most (83.16%) among six other MHS indicators. Community
provision of comprehensive emergency obstetric care strategy remained stagnant.
Districts with higher complete antenatal care share and C-sections in public
settings had lesser share of state's maternal deaths (R2 = 0.29, p = 0.004). 5
districts suffered perpetual inequity of MHS with relatively greater burden of
maternal deaths. CONCLUSION: First 6 years of national rural health mission
increased coverage of MHS and decreased regional inequity albeit non-uniformly.
Distribution of system driven interventions of complete ANC and C-sections appear
to determine decrease of maternal mortality in Karnataka.
PMID- 28490357
TI - Erratum to: Impact of medication adherence on renal function in comorbid patients
with type 2 diabetes and depression: protocol for a cohort study.
PMID- 28490356
TI - Transhepatic arterial infusion chemotherapy using a combination of miriplatin and
CDDP powder versus miriplatin alone in the treatment of hepatocellular carcinoma:
a randomized controlled trial.
AB - BACKGROUND: Based on promising results from a Phase I study of hepatic arterial
infusion chemotherapy using a combination of miriplatin and cisplatin powder (DDP
H) for unresectable hepatocellular carcinoma (UMIN-CTR000003541), a multicenter,
open-label, randomized phase II study was conducted to evaluate the efficacy and
safety of the combination therapy versus miriplatin monotherapy. METHODS:
Nineteen patients, five and fourteen Barcelona-Clinic Liver Cancer staging
classification A and B cases, respectively, were randomly assigned to receive
either miriplatin monotherapy (n = 9) or miriplatin/DDP-H combination therapy (n
= 10). DDP-H and/or miriplatin were administered through the hepatic arteries
supplying the lobes of the liver containing tumors, and progression free survival
was analyzed as a primary end point in addition to other secondary endpoints. The
corresponding therapy was repeated unless disease progression or severe adverse
events were recorded. RESULTS: The monotherapy or combination therapy was
performed for 15 or 36 sessions in total, respectively. Although there were no
significant differences between the two groups for treatment intervals (p = 0.96)
or the dose of miriplatin used in each session (p = 0.99), the progression free
survival and overall disease control rate were significantly better in the
combination therapy group (91 vs 423 days, p = 0.025; 40.0 vs 77.8%, p = 0.0025,
respectively). Consistent with these observations, a trend of a significantly
slower increase in des-gamma-carboxyprothrombin was observed, and the number of
treatment sessions was nearly significantly larger in the combination therapy
group (p < 0.0001, p = 0.057, respectively). Conversely, the median survival time
did not show a significant difference (706 days, monotherapy vs 733 days,
combination therapy; p = 0.40). A significant decrease in cholinesterase was
observed during the course of treatment only in patients receiving combination
therapy (r = -0.86, p < 0.0001). A few cases in both arms showed hematological
and/or non-hematological toxicities that were categorized as grade 1 (NCI-CTCAE).
CONCLUSIONS: The higher disease control effects with the combination of
miriplatin and DDP-H indicate that it is a promising alternative treatment for
cases with multiple HCCs, especially for those that can tolerate the treatment
without experiencing a reduction in hepatic reserve. TRIAL REGISTRATION: This
study was registered on 1 January 2012 with the University Hospital Medical
Information Network Clinical Trials Registry (
http://www.umin.ac.jp/ctr/index.htm , UMIN000004691).
PMID- 28490358
TI - Effectively engaging stakeholders and the public in developing violence
prevention messages.
AB - BACKGROUND: Preventing family violence requires that stakeholders and the broader
public be involved in developing evidence-based violence prevention strategies.
However, gaps exist in between what we know (knowledge), what we do (action), and
the structures supporting practice (policy). DISCUSSION: We discuss the broad
challenge of mobilizing knowledge-for-action in family violence, with a primary
focus on the issue of how stakeholders and the public can be effectively engaged
when developing and communicating evidence-based violence prevention messages. We
suggest that a comprehensive approach to stakeholder and public engagement in
developing violence prevention messages includes: 1) clear and consistent
messaging; 2) identifying and using, as appropriate, lessons from campaigns that
show evidence of reducing specific types of violence; and 3) evidence-informed
approaches for communicating to specific groups. Components of a comprehensive
approach must take into account the available research evidence, implementation
feasibility, and the context-specific nature of family violence. While strategies
exist for engaging stakeholders and the public in messaging about family violence
prevention, knowledge mobilization must be informed by evidence, dialogue with
stakeholders, and proactive media strategies. This paper will be of interest to
public health practitioners or others involved in planning and implementing
violence prevention programs because it highlights what is known about the issue,
potential solutions, and implementation considerations.
PMID- 28490359
TI - Cryopreservation of reproductive material before cancer treatment: a qualitative
study of health care professionals' views about ways to enhance clinical care.
AB - BACKGROUND: Cancer treatment can diminish fertility in women and men. The need
for fertility preservation is growing as increasing numbers of people survive
cancer. Cryostorage of reproductive material to preserve potential for conception
for cancer survivors has moved from being experimental to being a part of
clinical management of women and men who are diagnosed with cancer in their
reproductive years. There is little existing evidence about how fertility
preservation services can be enhanced to meet the complex needs of patients who
are diagnosed with cancer in their reproductive years. The aim of this research
was to inform clinical practice development by drawing on the collective
experience and knowledge of staff at well-established clinics that offer
fertility preservation before cancer treatment. METHODS: A qualitative research
model was adopted using semi-structured interviews with professionals involved in
the care of people who freeze reproductive material before cancer treatment. In
the state of Victoria, Australia, two large assisted reproductive technology
(ART) centres have been providing fertility preservation services for more than
two decades. An invitation to participate in a semi-structured interview about
clinical care in the context of fertility preservation was emailed to past and
current staff members. To capture diverse perspectives, informants were sought
from all relevant professions: fertility specialists, andrologists, nurses,
embryologists/scientists, counsellors, and administrative staff. Transcripts were
analysed thematically. RESULTS: Thirteen key informants were interviewed from
August 2013 to February 2014. The identified themes relating to enhancing
clinical care in a fertility preservation service were communication between
oncology and ART specialists; managing urgency; managing patients' expectations;
establishing and implementing protocols, systems, and data bases; and maintaining
contact with patients. CONCLUSION: The collective knowledge of this study's
informants, who represent multidisciplinary teams with more than two decades'
experience in fertility preservation, yields important insights into strategies
that fertility preservation services can employ to promote the integration of
oncology and fertility care, the psychosocial care of patients, data recording
and monitoring, and reporting of outcomes.
PMID- 28490360
TI - Stability and relative validity of the Neuromuscular Disease Impact Profile
(NMDIP).
AB - BACKGROUND: The aim of this study was to examine the stability and relative
validity (RV) of the Neuromuscular Disease Impact Profile (NMDIP) using criterion
related groups. In a previous study the NMDIP-scales showed good internal
consistency, convergent and discriminant validity. Known-groups analysis showed
that the NMDIP discriminates between categories of extent of limitations.
METHODS: A cross-sectional postal survey study was performed on patients
diagnosed with a NMD and registered at the Department of Neurology, University
Medical Center Groningen, the Netherlands. Participants were asked to complete
the preliminary NMDIP, the Medical Outcome study Short Form Questionnaire (SF
36), the World Health Organization Quality Of Life-abbreviation version (WHOQOL
bref), and two generic domain specific measures: the Groningen Activity
Restriction Scale (GARS) and the Impact on Participation and Autonomy
Questionnaire (IPAQ). The variables 'Extent of Limitations' and 'Quality of Life'
were used to create criterion-related groups. Stability over time was tested
using the Wilcoxon Signed Rank Test for paired samples and the intraclass
correlation coefficients for repeated measures. RV was examined by comparing the
ability of NMDIP with generic multidimensional health impact measures, and domain
specific measures in discriminating between criterion-related subgroups using the
Kruskal-Wallis H-test. RESULTS: Response rate was 70% (n = 702). The NMDIP-scales
showed sufficient stability over time, and satisfactory or strong RV. In general,
the NMDIP scales performed as well as or better than the concurrent measurement
instruments. CONCLUSIONS: The NMDIP proved to be a valid and reliable disease
targeted measure with a broad scope on physical, psychological and social
functioning.
PMID- 28490361
TI - Adducin family proteins possess different nuclear export potentials.
AB - BACKGROUND: The adducin (ADD) family proteins, namely ADD1, ADD2, and ADD3, are
actin-binding proteins that play important roles in the stabilization of membrane
cytoskeleton and cell-cell junctions. All the ADD proteins contain a highly
conserved bipartite nuclear localization signal (NLS) at the carboxyl termini,
but only ADD1 can localize to the nucleus. The reason for this discrepancy is not
clear. METHODS: To avoid the potential effect of cell-cell junctions on the
distribution of ADD proteins, HA epitope-tagged ADD proteins and mutants were
transiently expressed in NIH3T3 fibroblasts and their distribution in the
cytoplasm and nucleus was examined by immunofluorescence staining. Several
nuclear proteins were identified to interact with ADD1 by mass spectrometry,
which were further verified by co-immunoprecipitation. RESULTS: In this study, we
found that ADD1 was detectable both in the cytoplasm and nucleus, whereas ADD2
and ADD3 were detected only in the cytoplasm. However, ADD2 and ADD3 were
partially (~40%) sequestered in the nucleus by leptomycin B, a CRM1/exportin1
inhibitor. Upon the removal of leptomycin B, ADD2 and ADD3 re-distributed to the
cytoplasm. These results indicate that ADD2 and ADD3 possess functional NLS and
are quickly transported to the cytoplasm upon entering the nucleus. Indeed, we
found that ADD2 and ADD3 possess much higher potential to counteract the activity
of the NLS derived from Simian virus 40 large T-antigen than ADD1. All the ADD
proteins appear to contain multiple nuclear export signals mainly in their head
and neck domains. However, except for the leucine-rich motif
(377FEALMRMLDWLGYRT391) in the neck domain of ADD1, no other classic nuclear
export signal was identified in the ADD proteins. In addition, the nuclear
retention of ADD1 facilitates its interaction with RNA polymerase II and zinc
finger protein 331. CONCLUSIONS: Our results suggest that ADD2 and ADD3 possess
functional NLS and shuttle between the cytoplasm and nucleus. The discrepancy in
the subcellular localization of the ADD isoforms arises due to their different
nuclear export capabilities. In addition, the interaction of ADD1 with RNA
polymerase II and zinc-finger protein 331 implicates a potential role for ADD1 in
the regulation of transcription.
PMID- 28490362
TI - Different perceptions of narrative medicine between Western and Chinese medicine
students.
AB - BACKGROUND: Western medicine is an evidence-based science, whereas Chinese
medicine is more of a healing art. To date, there has been no research that has
examined whether students of Western and Chinese medicine differentially engage
in, or benefit from, educational activities for narrative medicine. This study
fills a gap in current literature with the aim of evaluating and comparing
Western and Chinese Medicine students' perceptions of narrative medicine as an
approach to learning empathy and professionalism. METHODS: An initial 10-item
questionnaire with a 5-point Likert scale was developed to assess fifth-year
Western medical (MS) and traditional Chinese medical (TCMS) students' perceptions
of a 4-activity narrative medicine program during a 13-week internal medicine
clerkship. Exploratory factor analysis was undertaken. RESULTS: The response rate
was 88.6% (412/465), including 270 (65.5%) MSs and 142 (34.5%) TCMSs, with a
large reliability (Cronbach alpha = 0.934). Three factors were extracted from 9
items: personal attitude, self-development/reflection, and emotional benefit,
more favorable in terms of enhancement of self-development/reflection. The
perceptions of narrative medicine by scores between the two groups were
significantly higher in TCMSs than MSs in all 9-item questionnaire and 3
extracted factors. CONCLUSIONS: Given the different learning cultures of medical
education in which these student groups engage, this suggests that undertaking a
course in Chinese medicine might enhance one's acceptance to, and benefit from, a
medical humanities course. Alternatively, Chinese medicine programmes might
attract more humanities-focused students.
PMID- 28490363
TI - Erratum to: Imported arboviral infections in Italy, July 2014-October 2015: a
National Reference Laboratory report.
PMID- 28490366
TI - Erratum to: Malaria parasite clearance.
PMID- 28490365
TI - Differentiation of mesenchymal stem cells into cardiomyocytes is regulated by
miRNA-1-2 via WNT signaling pathway.
AB - BACKGROUND: Bone marrow derived stem cells (BMSCs) have the potential to
differentiate into cardiomyocytes, but the rate of differentiation is low and the
mechanism of differentiation is unclear completely. Here, we aimed to investigate
the role of miR1-2 in differentiation of mouse BMSCs into cardiomyocyte-like
cells and reveal the involved signaling pathways in the procedure. METHODS: Mouse
BMSCs were treated with miR1-2 and 5-azacytine (5-aza). The expression of cardiac
cell markers: NKx2.5, cTnI and GATA4 in BMSCs were examined by qPCR. The
apoptosis rate was detected by flow cytometry and the activity of the Wnt/beta
catenin signaling pathway was evaluated by measuring the upstream protein of this
signaling pathway. RESULTS: After over-expression of miR1-2 in mouse BMSCs, the
apoptosis rate was significantly lower than the 5-aza group, while the
expressions of cardiac-specific genes: such as Nkx2.5, cTnI and GATA4 were
significantly increased compared to the control group and the 5-aza group.
Meanwhile, over-expression of miR1-2 in mouse BMSCs enhanced the expression of
wnt11, JNK, beta-catenin and TCF in the Wnt/beta-catenin signaling pathway. Use
of LGK-974, an inhibitor of Wnt/beta-catenin signaling pathway, significantly
reduced the expression of cardiac-specific genes and partially blocked the role
of the miR1-2. CONCLUSION: Over-expression of miR1-2 in mouse BMSCs can induce
them toward promoted cardiomyocyte differentiation via the activation of the
Wnt/beta-catenin signaling pathway. Compared to 5-aza, miR1-2 can induce
differentiation of BMSCs into cardiomyocytes more effectively with a less
cytotoxicity.
PMID- 28490364
TI - Sporadic late-onset nemaline myopathy: clinico-pathological characteristics and
review of 76 cases.
AB - BACKGROUND: Sporadic late-onset nemaline myopathy (SLONM) is a rare, late-onset
muscle disorder, characterized by the presence of nemaline rods in muscle fibers.
Phenotypic characterization in a large cohort and a comprehensive overview of
SLONM are lacking. METHODS: We studied the clinico-pathological features,
treatment and outcome in a large cohort of 76 patients with SLONM, comprising 10
new patients and 66 cases derived from a literature meta-analysis (PubMed, 1966
2016), and compared these with 15 reported HIV-associated nemaline myopathy (HIV
NM) cases. In 6 SLONM patients, we performed a targeted next-generation
sequencing (NGS) panel comprising 283 myopathy genes. RESULTS: SLONM patients had
a mean age at onset of 52 years. The predominant phenotype consisted of weakness
and atrophy of proximal upper limbs in 84%, of proximal lower limbs in 80% and
both in 67%. Other common symptoms included axial weakness in 68%, as well as
dyspnea in 55% and dysphagia in 47% of the patients. In 53% a monoclonal
gammopathy of unknown significance (MGUS) was detected in serum. The mean
percentage of muscle fibers containing rods was 28% (range 1-63%). In 2 cases
ultrastructural analysis was necessary to detect the rods. The most successful
treatment in SLONM patients (all with MGUS) was autologous peripheral blood stem
cell therapy. A targeted NGS gene panel in 6 SLONM patients (without MGUS) did
not reveal causative pathogenic variants. In a comparison of SLONM patients with
and without MGUS, the former comprised significantly more males, had more rapid
disease progression, and more vacuolar changes in muscle fibers. Interestingly,
the muscle biopsy of 2 SLONM patients with MGUS revealed intranuclear rods,
whereas this feature was not seen in any of the biopsies from patients without
paraproteinemia. Compared to the overall SLONM cohort, significantly more HIV-NM
patients were male, with a lower age at onset (mean 34 years). In addition,
immunosuppression was more frequently applied with more favorable outcome, and
muscle biopsies revealed a significantly higher degree of inflammation and
necrosis in this cohort. Similar to SLONM, MGUS was present in half of the HIV-NM
patients. CONCLUSIONS: SLONM presents a challenging, but important differential
diagnosis to other neuromuscular diseases of adult onset. Investigations for MGUS
and HIV should be performed, as they require distinct but often effective
therapeutic approaches. Even though SLONM and HIV-NM show some differences, there
exists a large clinico-pathological overlap between the 2 entities.
PMID- 28490368
TI - Erratum to: Genomic characterization of plant cell wall degrading enzymes and in
silico analysis of xylanases and polygalacturonases of Fusarium virguliforme.
PMID- 28490367
TI - Vitamin D deficiency among smear positive pulmonary tuberculosis patients and
their tuberculosis negative household contacts in Northwest Ethiopia: a case
control study.
AB - BACKGROUND: Vitamin D is a fat-soluble vitamin that increases the immunity
against tuberculosis (TB), decreases the re-activation of latent TB and reduces
the severity of active TB disease. Epidemiological studies on the prevalence of
vitamin D deficiency, and its association with TB showed inconsistent results in
different countries. This study was aimed to determine the prevalence of vitamin
D deficiency and its association with TB in Northwest Ethiopia. METHODS: A case
control study was conducted among smear positive pulmonary tuberculosis patients
and their household contacts without symptoms suggestive of TB. Study
participants were recruited at 11 TB diagnostic health facilities in North and
South Gondar zones of Amhara region between May 2013 and April 2015. The spot
morning-spot sputum samples and 5 ml blood sample were collected prior to
commencing TB treatment for the diagnosis of TB and serum vitamin D assay,
respectively. The diagnosis of TB was performed using smear microscopy and
GeneXpert. Serum vitamin D level was analyzed using VIDAS 25 OH Vitamin D Total
testing kits (Biomerieux, Marcy I'Etoile, France) on mini VIDAS automated
immunoassay platform. Vitamin D status was interpreted as deficient (<20 ng/ml),
insufficient (20-29 ng/ml), sufficient (30-100 ng/ml) and potential toxicity
(>100 ng/ml). RESULTS: Of the total study participants, 134 (46.2%) were vitamin
D deficient, and only 56 (19.3%) had sufficient vitamin D level. A total of 59
(61.5%) TB patients and 75 (38.7%) non TB controls were vitamin D deficient.
Results of multivariate logistic regression analyses showed a significantly
higher vitamin D deficiency among tuberculosis cases (p < 0.001), females (p =
0.002), and urban residents (p < 0.001) than their respective comparison groups.
Moreover, age groups of 35-44 (p = 0.001), 45-54 (p = 0.003) and >=55 (p = 0.001)
years had significantly higher vitamin D deficiency compared with age group <15
years. CONCLUSIONS: Vitamin D deficiency is highly prevalent among TB patients
and non TB controls in Ethiopia where there is year round abundant sunshine.
Study participants with tuberculosis, females, older age groups, and urban
residents had significantly higher prevalence of vitamin D deficiency. These
findings warrant further studies to investigate the role of vitamin D
supplementation in the prevention and treatment of tuberculosis in high TB burden
countries like Ethiopia.
PMID- 28490369
TI - Erratum to: Novel trigenic CACNA1C/DES/MYPN mutations in a family of hypertrophic
cardiomyopathy with early repolarization and short QT syndrome.
PMID- 28490370
TI - Behavioral interventions to promote adequate sleep among women: protocol for a
systematic review and meta-analysis.
AB - BACKGROUND: Short and poor sleep have been associated with adverse health
outcomes in adults, such as overweight/obesity and type 2 diabetes, especially
among women. Women therefore represent an important target for interventions
aimed at improving sleep and such interventions have been advocated to enhance
maternal, fetal, and infant health. This systematic review will assess the
efficacy or effectiveness of behavioral interventions aimed at promoting adequate
sleep among women. The primary outcomes will be changes in sleep duration and/or
sleep quality from baseline to post-intervention and to the last available follow
up measured either through self-reports or objectively. Secondary outcomes will
be assessing the behavior change techniques that are responsible for the changes
in sleep duration and quality among women. METHODS: Behavioral interventions that
are non-pharmacological and target either sleep directly or sleep hygiene
behaviors will be included. Randomized controlled trials, quasi-experimental, and
one-group pre-post studies will be included, but treated separately in the
analyses, given that a limited number of studies on the topic of sleep is
expected. MEDLINE/PubMed, PsycINFO, CINAHL, EMBASE, and Proquest Dissertations
and Theses will be investigated. There will be no restriction on the year of
publication of the articles, but we will include only the ones written in English
or French. Two authors will independently assess articles for eligibility and
will extract data using a standardized data extraction form that will have been
previously pilot-tested. The quality of the studies will be assessed using the
Effective Public Health Practice Project tool for quantitative study designs. The
intervention procedures will be classified according to the latest validated
taxonomy of behavior change techniques. If there is a sufficient number of
studies (k > 5), a meta-analysis of the results will be performed with a random
effect model. If the heterogeneity is high (I 2 >= 75%), it will be investigated
through sensitivity analyses and meta-regression. DISCUSSION: This review will
provide valuable information to those interested in promoting adequate sleep
among women and, hopefully, encourage additional research in this important field
to promote maternal, fetal, and infant health. SYSTEMATIC REVIEW REGISTRATION:
The study protocol was registered in PROSPERO in October 2016 (CRD42016049538).
PMID- 28490371
TI - Purification and properties of a novel quizalofop-p-ethyl-hydrolyzing esterase
involved in quizalofop-p-ethyl degradation by Pseudomonas sp. J-2.
AB - Quizalofop-p-ethyl (QPE) is a post-emergence herbicide that effectively controls
grass weeds and is often detected in the environment. However, the biochemical
and molecular mechanisms of QPE degradation in the environment remains unclear.
In this study, a highly effective QPE-degrading bacterial strain J-2 was isolated
from acclimated activated sludge and identified as a Pseudomonas sp., containing
the QPE breakdown metabolite quizalofop acid (QA) identified by Liquid
Chromatography-Ion Trap-Mass Spectrometry (LC-IT-MSn) analysis. A novel QPE
hydrolase esterase-encoding gene qpeH was cloned from strain J-2 and functionally
expressed in Escherichia coli BL21 (DE3). The specific activity of recombinant
QpeH was 198.9 +/- 2.7 U mg-1 for QPE with K m and K cat values of 41.3 +/- 3.6
MUM and 127.3 +/- 4.5 s-1. The optimal pH and temperature for the recombinant
QpeH were 8.0 and 30 degrees C, respectively and the enzyme was activated by
Ca2+, Cd2+, Li+, Fe3+ and Co2+ and inhibited by Ni2+, Fe2+, Ag+, DEPC, SDS, Tween
80, Triton X, beta-mercaptoethanol, PMSF, and pCMB. In addition, the catalytic
efficiency of QpeH toward different AOPP herbicides in descending order was as
follows: fenoxaprop-P-ethyl > quizalofop-P-tefuryl > QPE > haloxyfop-P-methyl >
cyhalofopbutyl > clodinafop-propargyl. On the basis of the phylogenetic analysis
and multiple sequence alignment, the identified enzyme QpeH, was clustered with
esterase family V, suggesting a new member of this family because of its low
similarity of amino acid sequence with esterases reported previously.
PMID- 28490372
TI - Erratum to: Does a quality improvement campaign accelerate take-up of new
evidence? A ten-state cluster-randomized controlled trial of the IHI's Project
JOINTS.
PMID- 28490373
TI - Thioredoxin-interacting protein links endoplasmic reticulum stress to
inflammatory brain injury and apoptosis after subarachnoid haemorrhage.
AB - BACKGROUND: Early brain injury (EBI) is considered a major contributor to the
high morbidity and mortality associated with subarachnoid haemorrhage (SAH). Both
of sterile inflammation and apoptosis are considered the important causes of EBI.
Recently, it was confirmed that thioredoxin-interacting protein (TXNIP) not only
participates in inflammatory amplification but also stimulates the apoptosis
signalling cascade pathway. However, whether the effects of TXNIP influence the
pathogenesis of SAH remains unclear. Here, we hypothesize that TXNIP activity
induced by endoplasmic reticulum stress (ER stress) may contribute to the
pathogenesis of EBI through pro-inflammatory and pro-apoptotic mechanisms.
METHODS: A total of 299 male Sprague-Dawley rats were used to create SAH models.
Resveratrol (RES, 60 mg/kg) and two TXNIP small interfering RNA (siRNA) were used
to inhibit TXNIP expression. The specific inhibitors of ER stress sensors were
used to disrupt the link between TXNIP and ER stress. SAH grade, neurological
deficits, brain water content and blood-brain barrier (BBB) permeability were
evaluated simultaneously as prognostic indicators. Fluorescent double-labelling
was employed to detect the location of TXNIP in cerebral cells. Western blot and
TUNEL were performed to study the mechanisms of TXNIP and EBI. RESULTS: We found
that TXNIP expression significantly increased after SAH, peaking at 48 h (0.48 +/
0.04, up to 3.2-fold) and decreasing at 72 h after surgery. This process was
accompanied by the generation of inflammation-associated factors. TXNIP was
expressed in the cytoplasm of neurons and was widely co-localized with TUNEL
positive cells in both the hippocampus and the cortex of SAH rats. We discovered
for the first time that TXNIP was co-localized in neural immunocytes (microglia
and astrocytes). After administration of RES, TXNIP siRNA and ER stress
inhibitors, TXNIP expression was significantly reduced and the crosstalk between
TXNIP and ER stress was disrupted; this was accompanied by a reduction in
inflammatory and apoptotic factors, as well as attenuation of the prognostic
indices. CONCLUSIONS: These results may represent the critical evidence to
support the pro-inflammatory and pro-apoptotic effects of TXNIP after SAH. Our
data suggest that TXNIP participates in EBI after SAH by mediating inflammation
and apoptosis; these pathways may represent a potential therapeutic strategy for
SAH treatment.
PMID- 28490374
TI - A serosurvey of selected cystogenic coccidia in Spanish equids: first detection
of anti-Besnoitia spp. specific antibodies in Europe.
AB - BACKGROUND: Equine besnoitiosis, caused by Besnoitia bennetti, and equine
protozoal myeloencephalitis (EPM), caused by Sarcocystis neurona and Neospora
hughesi are relevant equine diseases in the Americas that have been scarcely
studied in Europe. Thus, a serosurvey of these cystogenic coccidia was carried
out in Southern Spain. A cross-sectional study was performed and serum samples
from horses (n = 553), donkeys (n = 85) and mules (n = 83) were included. An in
house enzyme-linked immunosorbent assay (ELISA) was employed to identify a
Besnoitia spp. infection and positive results were confirmed by an a posteriori
western blot. For Neospora spp. and Sarcocystis spp., infections were detected
using in-house ELISAs based on the parasite surface antigens N. hughesi rNhSAG1
and S. neurona rSnSAG2/3/4. Risk factors associated with these protozoan
infections were also investigated. RESULTS: Antibodies against Besnoitia spp.,
Neospora spp. and Sarcocystis spp. infections were detected in 51 (7.1%), 46
(6.4%) and 20 (2.8%) of 721 equids, respectively. The principal risk factors
associated with a higher seroprevalence of Besnoitia spp. were the host species
(mule or donkey), the absence of shelter and the absence of a rodent control
programme. The presence of rodents was the only risk factor for Neospora spp.
infection. CONCLUSIONS: This study was the first extensive serosurvey of
Besnoitia spp. infection in European equids accomplished by two complementary
tests and gives evidence of the presence of specific antibodies in these
populations. However, the origin of the infection is still unclear. Further
parasite detection and molecular genotyping are needed to identify the causative
Besnoitia and Neospora species. Finally, cross-reactions with antibodies directed
against other species of Sarcocystis might explain the positive reactions against
the S. neurona antigens.
PMID- 28490376
TI - The effects of clinical supervision on supervisees and patients in cognitive
behavioral therapy: a study protocol for a systematic review.
AB - BACKGROUND: Clinical supervision by a senior therapist is a very common practice
in psychotherapist training and psychiatric care settings. Though clinical
supervision is advocated by most educational and governing institutions, the
effects of clinical supervision on the supervisees' competence, e.g., attitudes,
behaviors, and skills, as well as on treatment outcomes and other patient
variables are debated and largely unknown. Evidence-based practice is advocated
in clinical settings but has not yet been fully implemented in educational or
clinical training settings. The aim of this systematic review is to synthesize
and present the empirical literature regarding effects of clinical supervision in
cognitive-behavioral therapy. METHODS: This study will include a systematic
review of the literature to identify studies that have empirically investigated
the effects of supervision on supervised psychotherapists and/or the supervisees'
patients. A comprehensive search strategy will be conducted to identify published
controlled studies indexed in the MEDLINE, EMBASE, PsycINFO, and Cochrane Library
databases. Data on supervision outcomes in both psychotherapists and their
patients will be extracted, synthesized, and reported. Risk of bias and quality
of the included studies will be assessed systematically. DISCUSSION: This
systematic review will rigorously follow established guidelines for systematic
reviews in order to summarize and present the evidence base for clinical
supervision in cognitive-behavioral therapy and may aid further research and
discussion in this area. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016046834.
PMID- 28490377
TI - Cochlear implant electrode sealing techniques and related intracochlear pressure
changes.
AB - BACKGROUND: The inserted cochlear implanted electrode is covered at the site of
the round window or cochleostomy to prevent infections and leakage. In a
surgically hearing preservational concept, low intracochlear pressure changes are
of high importance. The aim of this study was to observe intracochlear pressure
changes due to different sealing techniques in a cochlear model. METHODS:
Cochlear implant electrode insertions were performed in an artifical cochlear
model and the intracochlear pressure changes were recorded in parallel with a
micro-pressure sensor positioned in the apical region of the cochlea model to
follow the maximum amplitude of intracochlear pressure. Four different sealing
conditions were compared: 1) overlay, 2) overlay with fascia pushed in, 3) donut
like fascia ring, 4) donut-like fascia ring pushed in. RESULTS: We found
statistically significant differences in the occurrence of maximum amplitude of
intracochlear pressure peak changes related to sealing procedure comparing the
different techniques. While the lowest amplitude changes could be observed for
the overlay technique (0.14 mmHg +/- 0.06) the highest values could be observed
for the donut-like pushed in technique (1.79 mmHg +/- 0.69). CONCLUSION: Sealing
the electrode inserted cochlea can lead to significant intracochlear pressure
changes. Pushing in of the sealing tissue cannot be recommended.
PMID- 28490375
TI - Structural and electrophysiological dysfunctions due to increased endoplasmic
reticulum stress in a long-term pacing model using human induced pluripotent stem
cell-derived ventricular cardiomyocytes.
AB - BACKGROUND: Long-term ventricular pacing has deleterious effects and becomes more
significant when cumulative percent ventricular pacing (Cum%VP) exceeds 40% of
time. However, cellular disturbances and pathways by which pacing leads to
myocardial disorders are not well understood. Attempts to resolve these questions
have been hampered by difficulties in obtaining human cardiac tissue and the
inability to build a longer-lasting (lasting longer than weeks) pacing model in
vitro. METHODS: Human induced pluripotent stem cell-derived ventricular
cardiomyocytes (VCMs) were cultured in the presence of electrical stimulation for
2 weeks. Quantitative structural and electrophysiological analyses were used to
define the functional disturbances of pacing. RESULTS: Compared to controls,
paced VCMs exhibited a remarkable reduction in the contractile protein
expression, an increased apoptosis ratio and electrophysiological remodelling in
a Cum%VP-dependent manner. Investigation of the protein expression levels
revealed that long-term pacing universally activated both ER stress and
downstream calpain. Moreover, the inhibition of calpain attenuated the adverse
effects on the structural remodelling and increased the ICa, L in paced VCMs.
CONCLUSIONS: The results demonstrated that pacing VCMs for 2 weeks in vitro led
to a series of structural and electrophysiological dysfunctions. The increased ER
stress and downstream calpain could be a central mechanism underlying the disease
pathogenesis. This finding could represent a new therapeutic target in the
management of long-term pacing patients.
PMID- 28490378
TI - Parotidectomy using the Harmonic scalpel: ten years of experience at a rural
academic health center.
AB - BACKGROUND: Parotidectomy is one of the most commonly performed procedures by
otorhinolaryngologists. Traditionally dissection is performed with a combination
of a steel scalpel and bipolar cautery; however, starting in the early 2000s, the
Harmonic scalpel has provided an alternative method for dissection and
hemostasis. The purpose of this study is to compare operative time, blood loss,
complications, and cost between the Harmonic scalpel and steel scalpel plus
bipolar cautery for superficial and total parotidectomy. METHODS: Retrospective
cohort of patients who underwent superficial or total parotidectomy with the
Harmonic or cold steel between 2000 and 2015. Across 255 patients, comparison
between operative time, blood loss, complications, and cost was performed.
RESULTS: Superficial parotidectomy was performed on 120 patients with the
Harmonic and 54 with steel scalpel. Total parotidectomy was performed on 59
patients using the Harmonic and 22 patients with cold steel. For superficial
parotidectomy, the Harmonic reduced operative time (216 +/- 42 vs. 234 +/- 54
min, p = 0.03) and decreased blood loss (28 +/- 19 vs. 76 +/- 52 mls, p < 0.05).
With total parotidectomy the Harmonic decreased operative time (240 +/- 42 vs.
288 +/- 78 min, p = 0.01) and reduced blood loss (38 +/- 21 mls vs. 85 +/- 55
mls, p < 0.05). There were no differences in complication rates between groups.
Harmonic use was associated with surgical cost reduction secondary to reduced
operative times. CONCLUSIONS: The Harmonic scalpel decreases blood loss and
operating time for superficial and total parotidectomy. Shorter operative times
may decrease the overall cost of parotidectomy.
PMID- 28490380
TI - Living with hypertrophic cardiomyopathy and an implantable defibrillator.
AB - BACKGROUND: ICDs efficiently terminate life-threatening arrhythmias, but
complications occur during long-term follow-up. Patients' own perspective is
largely unknown. The aim of the study was to describe experiences of hypertrophic
cardiomyopathy (HCM) patients with implantable defibrillators (ICDs). METHODS: We
analyzed 26 Swedish patient interviews using hermeneutics and latent content
analysis. RESULTS: Patients (aged 27-76 years) were limited by HCM especially if
it deteriorates into heart failure. The ICD implies safety, gratitude, and is
accepted as a part of the body even when inappropriate ICD shocks are
encountered. Nobody regretted the implant. Both the disease and the ICD affected
professional life and leisure time activities, especially at younger ages. Family
support was usually strong, but sometimes resulted in overprotection, whereas
health care focused on medical issues. Despite limitations, patients adapted,
accepted, and managed challenges. CONCLUSION: HCM patients with ICDs reported
good spirit and hope even though they had to adapt and accept limitations over
time.
PMID- 28490379
TI - A novel scoring system for predicting the neurologic prognosis prior to the
initiation of induced hypothermia in cases of post-cardiac arrest syndrome: the
CAST score.
AB - BACKGROUND: The aim of this study was to develop a scoring system for identifying
the post-cardiac arrest syndrome (PCAS) patients with a good potential for
recovery prior to the initiation of induced therapeutic hypothermia. METHODS: A
multi-center, retrospective, observational study was performed. Data of a total
of 151 consecutive adults who underwent induced hypothermia after cardiac arrest
(77 learning cases from two hospitals and 74 validation cases from two other
hospitals) were analyzed. RESULTS: In the learning set, 8 factors (initial
rhythm, witnessed status and time until return of spontaneous circulation, pH,
serum lactate, motor score according to the Glasgow Coma Scale (GCS), gray matter
attenuation to white matter attenuation ratio (GWR), serum albumin, and
hemoglobin) were found to be strongly correlated with the neurological outcomes.
A tentative scoring system was created from the learning data using these
factors, and the predictive accuracy (sensitivity and specificity) was evaluated
in terms of both internal validation (0.85 and 0.84) and external validation
(cutoff 50%: 0.95 and 0.90, 30%: 0.87 and 0.98, 15%: 0.67 and 1.00). Finally,
using all the data, we established a post-Cardiac Arrest Syndrome for induced
Therapeutic hypothermia (CAST) score to predict the neurologic prognosis prior to
initiation of induced hypothermia. CONCLUSIONS: The CAST score was developed to
predict the neurological outcomes of PCAS patients treated by induced
hypothermia. The likelihood of good recovery at 30 days was extremely low in PCAS
patients with a CAST score of <=15%. Prospective validation of the score is
needed in the future.
PMID- 28490381
TI - Palliative care in the neonatal unit: neonatal nursing staff perceptions of
facilitators and barriers in a regional tertiary nursery.
AB - BACKGROUND: Neonatology has made significant advances in the last 30 years.
Despite the advances in treatments, not all neonates survive and a palliative
care model is required within the neonatal context. Previous research has focused
on the barriers of palliative care provision. A holistic approach to enhancing
palliative care provision should include identifying both facilitators and
barriers. A strengths-based approach would allow barriers to be addressed while
also enhancing facilitators. The current study qualitatively explored perceptions
of neonatal nurses about facilitators and barriers to delivery of palliative care
and also the impact of the regional location of the unit. METHODS: The study was
conducted at the Townsville Hospital, which is the only regional tertiary
neonatal unit in Australia. Semi-structured interviews were conducted with a
purposive sample of eight neonatal nurses. Thematic analysis of the data was
conducted within a phenomenological framework. RESULTS: Six themes emerged
regarding family support and staff factors that were perceived to support the
provision of palliative care of a high quality. Staff factors included
leadership, clinical knowledge, and morals, values, and beliefs. Family support
factors included emotional support, communication, and practices within the unit.
Five themes emerged from the data that were perceived to be barriers to providing
quality palliative care. Staff perceived education, lack of privacy, isolation,
staff characteristics and systemic (policy, and procedure) factors to impact upon
palliative care provision. The regional location of the unit also presented
unique facilitators and barriers to care. CONCLUSIONS: This study identified and
explored facilitators and barriers in the delivery of quality palliative care for
neonates in a regional tertiary setting. Themes identified suggested that a
strengths-approach, which engages and amplifies facilitating factors while
identified barriers are addressed or minimized, would be successful in supporting
quality palliative care provision in the neonatal care setting. Study findings
will be used to inform clinical education and practice.
PMID- 28490383
TI - Erratum to: chTLR4 pathway activation by Astragalus polysaccharide in bursa of
Fabricius.
PMID- 28490382
TI - Premarital HIV testing in Malaysia: a qualitative exploratory study on the views
of major stakeholders involved in HIV prevention.
AB - BACKGROUND: HIV screening has existed in numerous methods as an important part of
HIV prevention efforts over the years. Premarital HIV testing for couples who
wish to marry has been implemented in a number of regions, which often operate in
a mandatory rather than voluntary basis and is considered a contentious issue,
with viewpoints held in favour and against. One such region is Malaysia which has
a policy of mandatory premarital HIV testing of prospective Muslim married
couples. The purpose of this study is to understand stakeholders' views on
premarital HIV testing given the Malaysian Islamic context. METHODS: 35 in-depth
face to face semi-structured interviews were undertaken with key stakeholder
groups involved in HIV prevention policy in Malaysia, namely, officials from the
Ministry of Health, religious leaders and people living with HIV. Participants
were recruited from the Klang Valley area, from July to December 2013, using
purposive sampling techniques. Inclusion criteria necessitated that participants
were over the age of 18 and provided full consent. Interviews were audiotaped,
followed a standardised topic guide, transcribed verbatim and analysed using a
framework analysis. RESULTS: Participants identified pre-marital HIV testing as
an effective HIV prevention policy implemented in Malaysia and was viewed, for
the most part, as a positive initiative across all stakeholders. Religious
leaders were supportive of testing as it provides a protective mechanism, in line
with the teachings of the Shariah, while Ministry of Health officials considered
it a normal part of their HIV prevention screening initiatives. However, there
were concerns surrounding issues such as confidentiality, counselling and
discrimination surrounding the test described by the PLHIV group. CONCLUSION: The
findings of this study show that among the participants interviewed was strong
support for mandatory premarital HIV testing, which could possibly expose the
vulnerability to HIV, reluctance to test and other areas in the HIV response in
Malaysia that need to be addressed. Furthermore, although international health
organisations are vehemently against mandatory premarital HIV testing, the strong
local support for such measures and the mismatch between these views is worth
exploring in more detail, given the cultural, social and religious context.
PMID- 28490384
TI - Neuroendocrine carcinoma of the breast: a review of 126 cases in China.
PMID- 28490385
TI - ALK-positive anaplastic large cell lymphoma undiagnosed in a patient with
tuberculosis: a case report and review of the literature.
AB - BACKGROUND: Due to a similarity between the features of lymphoma and the features
of tuberculosis, lymphoma may go unrecognized and undiagnosed in patients with
tuberculosis. CASE PRESENTATION: A 33-year-old Thai man presented to our center
with typical clinical manifestations of tuberculous lymphadenitis, with negative
tests for both acid-fast bacilli and fungi, and negative polymerase chain
reaction for Mycobacterial tuberculosis complex. The disease was not responding
to anti-tuberculosis treatment and he developed both pericardial effusion and
progressive lymphadenopathy. Large lymphoma cells were evident in the pericardial
effusion, and a review of the previous lymph node biopsies confirmed the
existence of ALK-positive anaplastic large cell lymphoma and tuberculous
lymphadenitis. Moreover, when the tests were repeated, he was found to be
positive for both acid-fast bacilli and Mycobacterial tuberculosis complex. The
presence of typical morphology of tuberculous lymphadenitis and inattentional
blindness may explain why the presence of large lymphoma cells was overlooked in
one of the previous lymph node biopsies. Our patient developed severe pneumonia
with profound septic shock due to carbapenem-resistant Enterobacteriaceae and
died within days. CONCLUSIONS: Given that tuberculosis and lymphoma can share
common features, this case highlights the importance of thoroughly reviewing all
foregoing relevant patient data (most notably pathology samples) in order to rule
out the presence of lymphoma that may exist within the shadow of typical
morphology of tuberculous lymphadenitis.
PMID- 28490386
TI - Pharmacists' Familiarity with and Institutional Utilization of Rapid Diagnostic
Technologies for Antimicrobial Stewardship.
AB - Rapid diagnostic technologies (RDTs) significantly reduce organism identification
time and can augment antimicrobial stewardship program (ASP) activities. An
electronic survey quantified familiarity with and utilization of RDTs by clinical
pharmacists participating in ASPs. Familiarity was highest with polymerase chain
reaction (PCR). Formal infectious diseases training was the only significant
factor influencing RDT familiarity. Infect Control Hosp Epidemiol 2017;38:863
866.
PMID- 28490387
TI - Serum carotenoid and retinol levels in African-Caribbean Tobagonian men with high
prostate cancer risk in comparison with African-American men.
AB - Black men are known to have a higher risk for prostate cancer (PC). Carotenoids
and retinol, linked to PC, have not been compared in different black populations
at risk. We examined serum carotenoid and retinol levels between PC-free African
Caribbean (AC) Tobagonian men with a high PC risk (high-grade prostatic
intraepithelial neoplasia, atypical foci or repeated abnormal PC screenings) and
African-American (AA) men with elevated serum prostate-specific antigen (PSA)
levels (>=4 ng/ml). AC men who participated in the 2003 lycopene clinical trial
and AA men who participated in the 2001-2006 National Health and Nutrition
Examination Survey were compared. Serum specimens were analysed for carotenoid
(beta-carotene, alpha-carotene, beta-cryptoxanthin, lutein/zeaxanthin and
lycopene) and retinol levels by isocratic HPLC. Quantile regression was used to
examine the association between serum carotenoid and retinol levels and black
ethnicity, overall and among men with elevated serum PSA. There were sixty-nine
AC men and sixty-five AA men, aged 41-79 years, included. AC men were associated
with lower serum lycopene and retinol levels, and higher serum alpha- and beta
carotenes and lutein/zeaxanthin levels compared with AA men, after adjusting for
age, BMI, ever smoked cigarettes, education and hypertension (P<=0.03). Among men
with elevated PSA, serum retinol was no longer statistically significant with
ethnicity (P=0.06). Possible differences may be attributed to dietary intake,
genetics and/or factors that influence bioavailability of these micronutrients.
Prospective studies are warranted that investigate whether these differences in
micronutrients between AC Tobagonian and AA men influence PC risk.
PMID- 28490388
TI - The ability of ewes with lambs to learn a virtual fencing system.
AB - The Nofence technology is a GPS-based virtual fencing system designed to keep
sheep within predefined borders, without using physical fences. Sheep wearing a
Nofence collar receive a sound signal when crossing the virtual border and a weak
electric shock if continuing to walk out from the virtual enclosure. Two
experiments testing the functionality of the Nofence system and a new learning
protocol is described. In Experiment 1, nine ewes with their lambs were divided
into groups of three and placed in an experimental enclosure with one Nofence
border. During 2 days, there was a physical fence outside the border, during Day
3 the physical fence was removed and on Day 4, the border was moved to the other
end of the enclosure. The sheep received between 6 and 20 shocks with an average
of 10.9+/-2.0 (mean+/-SE) per ewe during all 4 days. The number of shocks
decreased from 4.38+/-0.63 on Day 3 (when the physical fence was removed) to
1.5+/-0.71 on Day 4 (when the border was moved). The ewes spent on average 3%,
6%, 46% and 9% of their time outside the border on Days 1, 2, 3 and 4,
respectively. In Experiment 2, 32 ewes, with and without lambs, were divided into
groups of eight and placed in an experimental enclosure. On Day 1, the enclosure
was fenced with three physical fences and one virtual border, which was then
increased to two virtual borders on Day 2. To continue to Day 3, when there was
supposed to be three virtual borders on the enclosure, at least 50% of the ewes
in a group should have received a maximum of four shocks on Day 2. None of the
groups reached this learning criterion and the experiment ended after Day 2. The
sheep received 4.1+/-0.32 shocks on Day 1 and 4.7+/-0.28 shocks on Day 2. In
total, 71% of the ewes received the maximum number of five shocks on Day 1 and
77% on Day 2. The individual ewes spent between 0% and 69.5% of Day 1 in the
exclusion zone and between 0% and 64% on Day 2. In conclusion, it is too
challenging to ensure an efficient learning and hence, animal welfare cannot be
secured. There were technical challenges with the collars that may have affected
the results. The Nofence prototype was unable to keep the sheep within the
intended borders, and thus cannot replace physical fencing for sheep.
PMID- 28490389
TI - Monitoring and mass-trapping methodologies using pheromones: the lesser date moth
Batrachedra amydraula.
AB - The lesser date moth (LDM) Batrachedra amydraula is a significant pest of date
palm fruits. Previously, detection and monitoring of the pest was inaccurate due
to high costs of sampling with lifting machines. We report a practical system for
detection and monitoring of LDM based on pheromone traps and relevant models.
Dose-response experiments with LDM pheromone traps indicated a 1 mg lure is
optimal for monitoring. Delta traps with adhesive covering their entire inner
surface gave the highest captures while trap colour was unimportant. Sampling
pheromone traps throughout the night indicated male flight began at 1:00-2:00 and
reached a peak 2 h before sunrise. Monitoring traps exposed all year long in
Israel revealed three generations with different abundance. Trapping transects in
a date plantation indicated interference from a monitoring trap became minimal at
distances >27 m away. Inter-trap distances closer than this may lower efficiency
of monitoring and mass trapping in control programs. Our estimate of the circular
effective attraction radius (EARc) of a 1 mg delta trap for LDM (3.43 m) shows
this bait is among the most attractive compared with baits for other insects. We
developed encounter-rate equations with the pheromone trap EARc to model the
interplay between population levels, trap density and captures that are useful
for detection of invasive LDM and its control by mass trapping. The integrated
methodologies are applicable to many pest species.
PMID- 28490390
TI - Development and Evaluation of Acceptance and Commitment Therapy Delivered by
Psychologists and Non-Psychologists in an NHS Community Adult Mental Health
Service: a Preliminary Analysis.
AB - BACKGROUND: Previous studies have demonstrated that acceptance and commitment
therapy (ACT) is effective for depression and may be useful for complex
transdiagnostic clients. AIMS: To conduct a preliminary evaluation of whether ACT
is feasible and effective when delivered by psychologists and non-psychologists
for complex clients in a National Health Service (NHS) community mental health
service for adults. METHOD: Staff were trained in ACT and conducted one-to-one
therapy with clients. Measures on general mental health, depression, fusion and
values were given pre-therapy, post-therapy and at 3-month follow-up. RESULTS:
Standardized measures showed significant improvements post-therapy for global
mental health, depression, cognitive fusion and values post-treatment. These were
partially maintained at follow-up and remained after an intent-to-treat analysis.
There were no differences in outcomes between psychologists and non
psychologists. CONCLUSIONS: ACT may be delivered effectively with limited
training for complex cases in secondary care, though further research is needed.
PMID- 28490391
TI - MicroRNA-499-5p regulates porcine myofiber specification by controlling Sox6
expression.
AB - MicroRNAs (miRNAs) are a class of small non-coding RNAs that negatively regulate
gene expression of target messenger RNAs (mRNAs) and miRNAs have been proven to
play vital roles in skeletal muscle development. The miRNA-499-5p has been
reported to be negatively related with the expression of Sox6, a critical
transcription factor for the maintenance of fast-twitch skeletal muscle. In this
study, we amplified a length of 2012-bp mRNA that contains a 1512-bp porcine Sox6
(pSox6) 3'UTR from skeletal muscle of a Duroc*Landrace*Yorkshire pig. By
luciferase reporter assay we verified that pSox6 is a target of miR-499-5p. In
extensor digitorum longus and Soleus muscles of pigs, the expression levels of
miR-499-5p and pSox6 mRNA were also inversely correlated. Besides, overexpression
of miR-499-5p in porcine satellite cells promoted the expression of MyHC I and
MyHC IIa mRNA, along with a reduction of pSox6 mRNA. Taken together, these
results indicate that miR-499-5p may facilitate the oxidative myofibers formation
by downregulating pSox6 expression.
PMID- 28490392
TI - A systematic review of the heritability of specific psychopathic traits using
Hare's two-factor model of psychopathy.
AB - BACKGROUND: There have been no systematic reviews that investigated the
heritability of the two-factor model of psychopathy: interpersonal-affective and
behavioral. Our review aimed, first, to examine the heritability of general
psychopathic traits and, second, if genetic influences were suggested, to
determine the heritability of various traits related to the interpersonal
affective and behavioral factors of psychopathy. METHOD: A systematic literature
search was conducted using articles from the PsycINFO, Embase, Global Health,
Medline, PubMed, Web of Science, and Scopus databases (January of 1980 to
December of 2015) in order to identify eligible literature that reported on the
heritability of psychopathy-related traits. Papers were also found via manual
examination and reference tracking. Papers were subjected to exclusion criteria
and quality appraisal. We identified a total of 24 studies. RESULTS: Our results
were grouped into three categories: general, interpersonal-affective, and
behavioral. All these areas demonstrated modest to high heritability. The highest
heritability values were found in studies investigating callous-unemotional
behaviors. CONCLUSIONS: Heritability was found for all the psychopathic traits.
Future research should include endophenotypic approaches that explore gene
environment correlations, which could aid in identification of the behavioral
phenotype that is most amenable to early intervention by way of moderation of
genetic risk.
PMID- 28490393
TI - Assessing multiple goods and services derived from livestock farming on a nation
wide gradient.
AB - Livestock farming is an essential activity in many rural areas, where it
contributes to the maintenance of soil fertility and farmland biodiversity, as
well as to a set of social public goods including food security, rural vitality
and culture. However, livestock sustainability assessments tend to focus
primarily on environmental and economic dimensions; therefore, these valuations
might be limited because they do not consider the complete set of associated
goods and services (GS). Hence, a need exists to recognise the multiple
contributions provided by livestock to human well-being and society. The
objective of this study was to analyse the provision of multiple GS derived from
livestock across regions in France and empirically demonstrate sets of GS that
repeatedly appeared together. We designated these multiple GS provided by
livestock as contributions to productive, environmental, rural vitality and
cultural benefits that human populations derive directly or indirectly from
livestock agroecosystems. First, we combined expert knowledge with results of a
literature review to define a bundle of GS provided by livestock. We then
described indicators that quantified each good or service and screened national
databases to determine the availability of supporting data. Finally, we assessed
the GS and their relationships (synergies or trade-offs) on a nation-wide
gradient in France at the department level (Nomenclature of Territorial Units for
Statistics 3). Four main categories of GS were considered: provisioning (e.g.
food quantity and quality), environmental quality (e.g. biodiversity, landscape
heterogeneity, water quality), rural vitality (e.g. employment, rural dynamism)
and culture (e.g. gastronomy and landscape heritage). Four major types of GS
bundles were identified, which suggested strong contrasts among French rural
areas in terms of the nature of the GS that occurred together and their levels of
provision. GS bundles in France had a non-random spatial distribution. This study
represents an initial step towards developing a methodology to consider GS
bundles provided by livestock. Nonetheless, further research is needed to
understand socio-economic, environmental, political and geographic determinants
of the composition of GS bundles.
PMID- 28490394
TI - Synbiotic supplementation and the effects on clinical and metabolic responses in
patients with rheumatoid arthritis: a randomised, double-blind, placebo
controlled trial.
AB - Synbiotic intake may be associated with reduced inflammation in patients with
rheumatoid arthritis (RA) due to optimised inflammatory markers, oxidative stress
and insulin resistance. This research was conducted to assess the effects of
synbiotic supplementation on the clinical and metabolic parameters of patients
with RA. A total of fifty-four patients with RA were allocated into two groups to
receive either a synbiotic capsule (n 27) or a placebo (n 27) for 8 weeks in this
randomised, double-blind, placebo-controlled trial. Fasting blood samples were
taken at baseline and week 8 of the study to quantify related markers. After the
8-week intervention, compared with the placebo, synbiotic supplementation
resulted in a significant reduction in serum high-sensitivity C-reactive protein
(hs-CRP) levels (-1427.8 (sd 3267.2) v. +2833.4 (sd 5639.7) ng/ml, P=0.001). In
addition, compared with the placebo, synbiotic supplementation improved disease
activity score-28 joints (DAS-28) (-1.6 (sd 0.8) v. -0.3 (sd 0.5), P<0.001) and
visual analogue scales (VAS) pain (-30.4 (sd 18.7) v. -11.5 (sd 15.9), P<0.001).
In addition, a significant elevation in plasma nitric oxide (NO) (+0.8 (sd 4.4)
v. -2.6 (sd 4.5) umol/l, P=0.008), and significant reductions in insulin values (
13.8 (sd 26.4) v. +4.2 (sd 28.2) pmol/l, P=0.01), homoeostasis model of
assessment-estimated insulin resistance (HOMA-IR) (-0.5 (sd 1.0) v.+0.1 (sd 1.1),
P=0.03) and homoeostatic model assessment-beta-cell function (HOMA-B) (-9.4 (sd
17.9) v. +3.3 (sd 18.9), P=0.01) following supplementation with the synbiotic
compared with the placebo. Compared with the placebo, synbiotic supplementation
also resulted in a significant increase in plasma GSH (+36.6 (sd 63.5) v. -58.5
(sd 154.4) umol/l, P=0.005). Overall, our study demonstrated that synbiotic
supplementation for 8 weeks among patients with RA had beneficial effects on hs
CRP, DAS-28, VAS, NO, insulin levels, HOMA-IR, HOMA-B and GSH levels.
PMID- 28490395
TI - Factors associated with pre-slaughter mortality in turkeys and end of lay hens.
AB - Pre-slaughter transportation may affect poultry welfare and mortality rates. A
retrospective analysis was conducted to examine the effect of environmental,
management and individual factors on the percentage of dead birds during pre
slaughter transportation (dead-on-arrival, DOA). The variables accounted for in
the analyses included: environmental temperature, travel duration, genetic line,
gender, crate type and crate stocking density. Among the 41 452 loads of turkeys
(34 696 388 birds) and 3241 of end of lay hens (21 788 124 birds) transported to
three large abattoirs in northern Italy in a 3-year period, the median DOA was
0.14% in turkeys, and 0.38% in hens. In turkeys, travel duration longer than 30
min, temperature higher than 26 degrees C and high in-crate densities were
associated with increased DOA. In winter (?2 degrees C), high stocking densities
did not reduce the mortality risk from cold stress; on the contrary, for stocking
densities either near to or just above the maximum density in EC Reg. 1/2005, the
DOA risk was greater than for loads with densities of 10 kg/m2 less than the EC
maximum. Male birds and specific genetic lines also showed a higher DOA. In hens,
transportation lasting longer than 2 h and the brown-feathered breed were
associated with higher DOA. Dead-on-arrival progressively increased with travel
duration, remaining constant between 4 and 6 h and peaking at 8 h (median:
0.57%). The maximum DOA increase was detected during winter. These results show
that several species-specific factors may lead to increased risk of mortality.
PMID- 28490396
TI - Prognostic factors for therapeutic sialendoscopy.
AB - OBJECTIVE: To review our experience with therapeutic sialendoscopy in both the
submandibular and parotid glands in order to determine prognostic factors and
improve successful outcomes. STUDY DESIGN: Single-centre, retrospective chart
review. METHOD: The medical records of patients who had undergone sialendoscopy
for sialolithiasis were reviewed, and demographic details, stone data (location,
size, multiplicity, mobility), and operative technique and success were recorded.
RESULTS: Eighty-five patients were included: 70 patients with submandibular
stones and 15 with parotid stones. Sialendoscopy was successful in all cases.
Complete endoscopic removal was successful in 51 per cent of patients with
submandibular stones and 47 per cent of those with parotid stones. Size (less
than 5 mm) and distance from the papilla (less than 3 cm) were significant
factors affecting success for patients with submandibular duct stones. However,
this was not the case for patients with parotid duct stones, with neither
variable achieving significance; nevertheless, numbers were small. CONCLUSION:
Stone size and location significantly affect the success of therapeutic
sialendoscopy in submandibular glands.
PMID- 28490398
TI - The microscope and the endoscope.
PMID- 28490397
TI - Aortic dissection and cystinosis: is there any relationship?
AB - Cystinosis is a rare, autosomal-recessive genetic disorder. The kidneys are
commonly involved, as there is cystinosin protein malfunction, and nephropathic
cystinosis ensues. Although cardiac and vascular involvements are rare, we
describe a unique case of aortic dissection in a 25-year-old female with
cystinosis. We discuss the possible aetiologies of aortic dissection in this
condition.
PMID- 28490399
TI - Specific immunoglobulin E and immunoglobulin G4 toward major allergens of house
dust mite during allergen-specific immunotherapy.
AB - BACKGROUND: Specific immunoglobulin E (sIgE) and sIgG4 to house-dust mite (HDM)
major allergens during allergen immunotherapy (AIT) and their clinical relevance
remain unclear. OBJECTIVE: To investigate the variation of sIgE and sIgG4 to HDM
major allergens and the correlation with clinical responses during AIT in
patients with allergic rhinitis. METHODS: Thirty-nine patients with HDM allergy
were divided into the AIT group (taking immunotherapy) and the control group
(medication only use). The AIT group was subdivided into negative clinical
responses to AIT (nAIT) group and positive clinical responses to AIT (pAIT) group
according to symptom relief and subjective evaluation. sIgE and sIgG4 to
Dermatophagoides pteronyssinus (Dp) and Dermatophagoides farinae (Df), and their
group 1 and group 2 major allergens (Dp1, Df1, Dp2, and Df2) were measured before
AIT, at 6 months, and at 1 year after starting AIT. RESULTS: Dp2, Df, and Df2
sIgE values decreased significantly in the pAIT group versus the nAIT group after
1 year of AIT (median values of delta change were Dp2, -10.09 versus 5.89 kU/L, p
= 0.001; median values of Df were -9.69 versus 17.54 kU/L, p = 0.004; median
values of Df2 were -11.06 versus 20.08 kU/L, p = 0.013). There was a robust
increase in the sIgG4 values to Dp, Df, and their major allergens in both the
pAIT and the nAIT groups overall after 1 year of treatment. CONCLUSION: Patients
with a positive response to AIT showed a significant reduction of HDM group 2
sIgEs compared with those with a negative response to AIT, which indicated that a
decrease in group 2 sIgEs could be a marker that reflected AIT clinical efficacy.
PMID- 28490400
TI - Association of pediatric allergic rhinitis with the ratings of attention
deficit/hyperactivity disorder.
AB - BACKGROUND: Allergic rhinitis (AR) is currently the most prevalent allergic
disease in children and adolescents. OBJECTIVE: Surveys conducted by population
based studies of East Asia revealed an increased prevalence of behavioral
disorders in patients with AR. Thus, in this study, we explored the prevalence of
attention-deficit/hyperactivity disorder (ADHD) in pediatric patients with AR.
METHODS: A total of 333 children (6-12 years of age) with AR and a total of 322
age-matched controls were included in this study. An otorhinolaryngologist
diagnosed all AR cases and evaluated the severity of the disease. Skin-prick test
results for 18 major allergens, Paediatric Rhinoconjunctivitis Quality of Life
Questionnaire (PRQLQ), Child Behavior Checklist (CBCL), and Swanson, Nolan, and
Pelham version IV (SNAP-IV) scores were recorded. RESULTS: In total, 320 age
matched controls and 323 children with AR completed the study. With respect to
the Total Nasal Symptom Score and the PRQLQ, the condition of the experimental
group was more serious than that of the controls. The scores on the
hyperactivity/impulsivity and inattention subscales, which evaluate ADHD
symptoms, and those on the CBCL subscales were significantly higher in patients
with AR than in the controls (all p values were <0.01). From the results of the
Pearson correlation, we deduced that there were significant positive correlations
between the AR-related data and each subscale of the CBCL and SNAP-IV in the AR
group. Moreover, two basic characteristics (males and environmental exposure to
tobacco smoke) present significant positive and age showed a significant negative
correlations affect ADHD symptom in both the AR group and the control group.
Also, in the "pure AR" group, hierarchical regression analyses were performed to
determine the subtests of the PRQLQ, which are significant predictors of SNAP-IV
and CBCL. CONCLUSIONS: Apart from AR per se, the possible comorbidities of
impulsivity and inattention are important when managing children with AR. It is
essential to evaluate the symptoms of ADHD in children and adolescents with AR.
PMID- 28490402
TI - International Frontal Sinus Anatomy Classification and anatomic predictors of low
lying anterior ethmoidal arteries.
AB - BACKGROUND: The International Frontal Sinus Anatomy Classification (IFAC) was
introduced to more accurately characterize ethmoid and frontal sinus
pneumatization patterns. The prevalence of IFAC cells and their anatomic
associations have not been described. OBJECTIVE: The goal was to examine the
prevalence of IFAC cells and determine radiologic features associated with a low
lying anterior ethmoidal artery (LAEA). METHODS: Imaging of adult patients who
underwent computed tomographies from January 2015 to March 2016 were
retrospectively reviewed by using the IFAC classification. We also measured the
distance from the skull base to the anterior ethmoidal artery (AEA), the height
of the lateral lamella of the cribriform plate, and anterior-posterior diameter
from the anterior wall of the frontal sinus to the skull base (APF). Patients
with a history of sinus surgery, trauma, malignancy, or congenital anomaly were
excluded. Statistical analysis was performed by using Pearson correlation
coefficients and chi2 tests. RESULTS: A total of 95 patients met the inclusion
criteria. There was a significant association between supraorbital ethmoid cells
and an LAEA (p < 0.001), with a significant effect size (phi = 0.276, p = 0.007).
An inverse relationship was observed between Keros type I classification I and an
LAEA (p < 0.001), with a significant effect size (phi = -0.414, p = 0.000).
Significant associations were found between the AEA distance from the skull base
and the cribriform lateral lamella height (R = 0.576, p < 0.001). In addition,
there was a significant association between the AEA distance from the skull base
and the APF (R = 0.497, p < 0.001). CONCLUSION: The presence of a supraorbital
ethmoid cell and a wide APF were associated with an LAEA. There was a significant
relationship between Keros type I classification and the AEA adjacent to the
skull base. Delineation of these anatomic relationships may be helpful during
endoscopic sinus surgery to avoid complications.
PMID- 28490401
TI - Immunopathologic characteristics of nasal polyps in adult Koreans: A single
center study.
AB - BACKGROUND: Chronic rhinosinusitis with nasal polyps (NP) (CRSwNP) is classified
into eosinophilic and noneosinophilic types based on the level of tissue
eosinophilia. The immunopathologic features of Western and Asian CRSwNP differ.
OBJECTIVES: The aim of this study was to investigate the immunopathologic
characteristics of Korean patients with eosinophilic NP versus noneosinophilic NP
and those with atopic NP versus nonatopic NP. METHODS: Tissue samples were
collected from 81 patients with NP and 24 controls. The clinical characteristics
of all the patients were analyzed. Tissues were investigated for expression of
chemical mediators, including interleukin (IL) 5, IL-10, IL-17, interferon-gamma,
and tumor growth factor-beta1; transcription factors, including GATA binding
protein 3 (GATA-3), forkhead box P3 (Foxp3), retinoic acid-related orphan
receptor C (RORC), and T-box transcription factor (T-bet), and extracellular
matrix, including collagen type I, fibronectin, tissue inhibitor of
metalloproteinase 1, and matrix metalloproteinase (MMP) 9. RESULTS: Although the
clinical characteristics differed between eosinophilic and noneosinophilic NPs,
atopic status did not affect the clinical findings of CRSwNP. Both T-helper 1 and
2 cytokines increased significantly in patients with eosinophilic NP, but atopic
status did not affect the expression of any of the chemical mediators. GATA-3
messenger RNA (mRNA) expression increased significantly in patients with
eosinophilic NP, and RORC mRNA expression increased significantly in patients
with noneosinophilic NP. T-bet, RORC, and Foxp3 mRNA expression increased
significantly in patients with nonatopic NP. Fibronectin and MMP-9 mRNA
expression increased significantly in patients with noneosinophilic NP, whereas
only MMP-9 mRNA increased significantly in patients with eosinophilic and those
with noneosinophilic NP. CONCLUSION: The immunopathologic characteristics
differed between eosinophilic NP and noneosinophilic NP and between atopic NP and
nonatopic NP. The different underlying pathogenic processes may influence the
development of Korean NP.
PMID- 28490403
TI - Effects of changes in nasal volume on voice in patients after endoscopic
endonasal transsphenoidal surgery.
AB - OBJECTIVE: To investigate a potential correlation between changes in voice and
changes in nasal volume. METHODS: The endoscopic endonasal transsphenoidal
approach (EETSA) was performed on 120 patients between February 2009 and August
2016 by using the bilateral modified nasoseptal rescue flaps method. All the
patients were subjected to pre- and postoperative paranasal computed tomography
(CT) and voice evaluations by using acoustic analyses, a nasometer to measure the
nasalance, and determination of the voice handicap index (VHI). Paranasal CT and
the medical image processing software were used to calculate changes in nasal
cavity volume in three nasal sections. RESULTS: Enlargement of the nasal cavity
after surgery was evident in all three areas (anteronasal, p < 0.001; midnasal, p
= 0.005; postnasal, p = 0.025). In addition, EETSA resulted in significantly
higher mean nasalance scores for the oronasal passage (p < 0.001) and nasal
passage (p < 0.001); more frequency perturbation (jitter) (p < 0.001) and
amplitude perturbation (shimmer) (p < 0.001); and higher grade, roughness,
breathiness, asthenia, and strain scores (p < 0.001), and VHI (p = 0.01).
However, only changes in the nasal volume after EETSA correlated with postnasal
hypernasality (r = 0.2; p = 0.029). CONCLUSION: Although changes in nasal volume,
voice, and speech may develop after EETSA, we found that changes in nasal volume
were not correlated with changes in any voice-quality measure. However, the
postnasal cavity was the region most dramatically affected by EETSA, and
postnasal volume changes after surgery may be associated with hypernasal speech.
PMID- 28490404
TI - Causes of dacryocystorhinostomy failure: External versus endoscopic approach.
AB - OBJECTIVES: To compare the causes of failure between external and endoscopic
dacryocystorhinostomy (DCR) techniques for the treatment of lacrimal obstruction.
STUDY DESIGN: A retrospective cohort study. METHODS: The study population
consisted of 53 consecutive patients who underwent revision endoscopic DCR from
2002 to 2013 for lacrimal duct obstruction. Identified causes of previous DCR
failure were compared between patients whose initial surgery was performed
through an external versus an endoscopic approach. RESULTS: Reasons for surgical
failure after external (n = 21) versus endoscopic (n = 32) DCR included
cicatricial closure of the internal lacrimal ostium (52.4 versus 53.1%; p =
0.96), inadequate removal of bone overlying the lacrimal sac (23.8 versus 9.4%; p
= 0.15), sump syndrome (9.5 versus 9.4%; p = 0.99), and intranasal adhesions (65
versus 37.5%; p = 0.05). Adhesions that involved the middle turbinate were a
particularly impactful cause of failure when the DCR was performed through an
external versus the endoscopic approach (57.1 versus 28.1%; p = 0.04).
Septoplasty was more likely to be needed at the time of revision surgery if the
initial procedure was performed externally (71.1 versus 15.6%; p = 0.02).
Surgical success rates for revision DCR were comparable between the groups (75.0%
external versus 73.3% endoscopic; p = 0.90), with a mean follow-up of 12.7
months. CONCLUSION: DCR failure associated with intranasal adhesions was more
likely to occur when the surgery was performed through an external rather than an
endoscopic approach. Endoscopic instrumentation allowed for identification and
correction of intranasal pathology at the time of DCR, including an enlarged
middle turbinate or a deviated septum, which may improve surgical outcome.
PMID- 28490405
TI - Utility of early postoperative imaging after combined endoscopic and open ventral
skull base surgery.
AB - PURPOSE: Immediate postoperative imaging is frequently obtained after combined
skull base surgery (SBS) with endoscopic endonasal and open transcranial
approaches. The importance of early postoperative imaging for detecting
complications in these patients is still debatable. In this study, we
investigated the clinical utility of early postoperative imaging after combined
SBS for determination of postoperative complications. METHODS: A retrospective
chart analysis of 21 cases of combined SBS between 2009 and 2015 was performed.
Data on postoperative computed tomography (CT) and magnetic resonance imaging
(MRI), and the hospital course were collected. We separated interpretations of
postoperative imaging into two groups: (1) when using the radiologist's
interpretation alone, and (2) when using the surgeon's knowledge of the case in
conjunction with imaging. RESULTS: Forty-two postoperative scans were obtained
(21 CT, 21 MRI) within 48 hours of surgery. There was a significant statistical
difference between imaging interpretation by surgeons and radiologists for CT
interpretation only. For CT interpretation the true positive (TP), false positive
(FP), true negative (TN), and false negative (FN) rates for radiologists (TP,
0/21; FP, 6/21; TN, 11/21; FN, 4/21) slightly deviated from surgeons'
interpretation (TP, 1/21 [p = 0.9999]; FP, 0/21 [p = 0.0207]; TN, 17/21 [p =
0.1000]; FN, 3/21 [p = 1.000]). Rates for MRI interpretation by both groups were
nearly identical, with no significant difference found. Overall, four patients
experienced seven postoperative complications, which led to a complication rate
of 19.0% (4/21). The patients exhibited clinical symptoms in all instances of
postoperative complications that required further intervention. CONCLUSION: The
benefit of early postoperative imaging to detect complications after combined SBS
was limited. In this cohort of patients, positive imaging findings' effects on
patient management were dictated by the presence of supporting clinical symptoms.
PMID- 28490406
TI - Closure of nasal septal perforations with a polydioxanone plate and
temporoparietal fascia in a closed approach.
AB - BACKGROUND: Septal perforation closure is still often invasive and complex, with
relatively low closure rates. OBJECTIVES: We aimed to provide the first results
of a case series of 20 patients with nasal septal perforations who underwent
septal perforation repair by both an open and a minimally invasive technique by
using a graft that consisted of temporoparietal fascia and a polydioxanone (PDS)
plate without mucosal flaps. Between 2014 and 2016, we tested, for the first
time, the feasibility of the insertion of this graft via a hemitransfixion
incision at our institution. The rationale for the closed approach was to avoid
any visible nasal scars. We reported our results of both approaches. METHODS: The
septal perforations were closed by insertion of a graft, which consisted of a
0.25-mm PDS flexible plate enveloped by temporoparietal fascia, into the
perforation. The insertion of the graft was performed either via a columellar
incision (open approach) or via a cosmetically advantageous hemitransfixion
incision (closed approach) in an underlay technique. No attempts were made to
close the perforation by mucosal flap rotation and/or advancement. Protective
silastic sheeting to both sides of the perforation provided fixation to the graft
while natural mucosal healing occurred over the perforation in the course of 3 to
8 weeks. RESULTS: Eighteen of 20 perforations were closed by mucosa at the last
follow-up. The mean follow-up was 8.7 months. Thirteen patients had surgery via
the closed approach. CONCLUSION: We showed, for the first time, that the
insertion of a graft that consisted of a PDS flexible plate enveloped in
temporoparietal fascia via a hemitransfixion incision was feasible and resulted
in complete mucosal closure of nasal septal perforations in most patients. By
performing the hemitransfixion incision, we avoided any visible nasal scars.
PMID- 28490407
TI - The application of a free nasal floor mucoperiosteal graft in endoscopic sinus
surgery.
AB - BACKGROUND: Numerous reconstructive techniques and materials have been reported
for repair of skull base defects, cerebrospinal fluid (CSF) leaks, and coverage
of denuded bone, including pedicled vascularized flaps and free mucosal grafts.
OBJECTIVE: This study described our technique of harvesting and transferring a
free nasal floor mucoperiosteal graft and discussed our experience with the
application of this technique. METHODS: A retrospective review of 19 patients
(mean age, 53.7 years; 13 men, 6 women) treated with image-guided endoscopic
sinus surgery for chronic rhinosinusitis or tumors. Intraoperative free mucosal
graft repair was performed for large skull base defects after resection of skull
base tumor (n = 7), CSF leak (n = 12), and iatrogenic CSF leak (n = 7). Repair
was performed in an overlay or an underlay fashion, with a multilayer approach in
cases of a large skull base defect. Patients underwent endoscopic assessment at 6
days, 5 weeks, and 12 weeks after surgery for assessment of healing and of CSF
leak. The patients were followed up for a mean of 8.7 months. RESULTS: Minimal
crusting was identified at the donor site in all the patients at 6 days, with no
evidence of CSF leak. In cases of exposed bone and/or mucosal stripping,
hyperostosis at the recipient graft site was avoided. All the patients had
complete healing at the donor site and the recipient site, with minimal morbidity
at 5 and 12 weeks, and no evidence of recurrent CSF leak. CONCLUSION: The use of
nasal floor mucoperiosteal free grafts in endoscopic surgery offered the
advantage of ease of harvest, coverage of large defects, and multiple
applications of use, with minimal donor-site morbidity.
PMID- 28490408
TI - Endoscopic resection of sinonasal mucosal melanoma has comparable outcomes to
open approaches.
AB - BACKGROUND: Endoscopic endonasal resection (EER) of sinonasal mucosal melanoma
(SMM) is a newer surgical alternative to traditional external and/or open
resection (OR). Studies on long-term outcomes are necessary to validate EER for
this aggressive sinonasal malignancy. OBJECTIVE: To compare outcomes of EER
versus OR in SMM. METHODS: A case series of patients who underwent surgical
resection of SMM at a tertiary-care institution (2000-2015) was studied
retrospectively. Demographics, tumor site and stage, surgical approach, surgical
margin status, local control, and survival were compared between those who
underwent EER and OR. RESULTS: Twenty-two patients met inclusion criteria. Nine
underwent EER and 13 underwent OR. The mean age in the EER and OR groups was
similar, 78.7 and 72.3 years, respectively. Two-thirds of patients were women
(EER, 66.7%; OR, 61.5%). The nasal cavity was the most common primary tumor site
(EER, 77.8%; OR, 84.6%). The local tumor stage in both groups was similar, with
the majority of cases being T4 (EER, 55.6%; OR, 61.5%; p = 0.99). Negative
margins were achieved in all EERs and in 69.2% of ORs. Median follow-up was 25.0
months for the overall group (range, 1.7-172.9 months), 32.6 months (range, 3.4
58.7 months) for EER and 14.1 months (range, 1.7-172.9 months) for OR cohorts.
The 5-year overall survival was statistically similar in both groups (EER, 53.3%;
OR, 22.7%; p = 0.214) as was disease-free survival (EER, 55.6%; OR, 22.8%; p =
0.178). Local control, however, was significantly higher in the EER cohort (EER,
85.7%; OR, 37.6%; p = 0.026). CONCLUSION: In carefully selected patients with
sinonasal melanoma, endoscopic surgery with an experienced team may offer
comparable survival and improved local control over open surgery. Prospective,
multicentered studies with larger cohorts are needed to validate these results.
PMID- 28490409
TI - Endoscopic-guided coblation treatment of nasal telangiectasias in hereditary
hemorrhagic telangiectasia: "How I do it".
AB - INTRODUCTION: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal
dominant disease that leads to frequent epistaxis. It can have a significant
impact on quality of life. Many reports exist regarding various therapies to
address the epistaxis. MATERIALS AND METHODS: We presented our technique for
addressing the epistaxis associated with HHT. RESULTS: Patients are treated in
the operating room while they are under general anesthesia. A local anesthetic is
injected sublabially, and oxymetazoline is dripped into the nose. The coblation
wand is used to treat the telangiectasias. Bevacizumab is then injected into the
nasal cavity bilaterally. CONCLUSION: The coblation wand, with or without
adjunctive bevacizumab injection, is a technically feasible intervention for
patients with HHT that all providers can perform.
PMID- 28490410
TI - Recurrence of Sinonasal Inverted Papilloma Following Surgical Approach: A Meta
Analysis.
PMID- 28490411
TI - Is the Counterweight Program a feasible and acceptable option for structured
weight management delivered by practice nurses in Australia? A mixed-methods
study.
AB - Nurse-led weight management programs, like the Counterweight Program in the
United Kingdom, may offer a way for Australian general practices to provide
weight management support to adults who are overweight or obese. During
Counterweight, nurses provide patients with six fortnightly education sessions
and three follow-up sessions to support weight maintenance. This study examined
the feasibility, acceptability and perceived value of the Counterweight Program
in the Australian primary care setting using a mixed-methods approach. Six
practice nurses, from three general practices, were trained and subsidised to
deliver the program. Of the 65 patients enrolled, 75% (n=49) completed the six
education sessions. General practitioners and practice nurses reported that the
training and resource materials were useful, the program fitted into general
practices with minimal disruption and the additional workload was manageable.
Patients reported that the program created a sense of accountability and provided
a safe space to learn about weight management. Overall, Counterweight was
perceived as feasible, acceptable and valuable by Australian practice staff and
patients. The key challenge for future implementation will be identifying
adequate and sustainable funding. An application to publically fund Counterweight
under the Medicare Benefits Schedule would require stronger evidence of
effectiveness and cost-effectiveness in Australia.
PMID- 28490412
TI - Improving community access to terminal phase medicines in Australia:
identification of the key considerations for the implementation of a 'core
medicines list'.
AB - During the terminal phase, access to medicines is critical for people wishing to
spend their last days of life at home. Yet, access to medicines can be
problematic. The aim of this study was to report the perspectives of specialist
and generalist health professionals (HPs) on the issues of community access to
medicines for this vulnerable group. A qualitative descriptive study design
investigated the views of HPs working in palliative care roles in South
Australia. Nurses, doctors and pharmacists described their experiences of
accessing medicines for management of terminal phase symptoms during semi
structured focus group discussions. Content analysis identified six themes
including: 'Medication Supply', 'Education and Training', 'Caregiver Burden',
'Safety', 'Funding' and 'Clinical Governance'. Future projects should aim to
address these themes when developing strategies for the management of people
wishing to die at home.
PMID- 28490413
TI - Risk factors for appendiceal involvement in women with epithelial ovarian cancer.
AB - OBJECTIVE: To evaluate the risk factors for appendiceal involvement in women with
epithelial ovarian cancer (EOC) who underwent appendectomy at the time of initial
surgery. MATERIAL AND METHODS: Patients with a final diagnosis of EOC who
underwent appendectomy at the time of initial surgery were evaluated
retrospectively. Risk factors related to the presence of appendiceal involvement
were analyzed. RESULTS: A total of 210 patients underwent appendectomy during
staging surgery. Appendiceal involvement was detected in 61 patients. No women
with apparent clinical early-stage tumors had evidence of isolated metastatic
disease to the appendix; therefore, no upstaging was detected due to solitary
appendiceal involvement in this group of patients. For all patients, univariate
analysis of the appendiceal involvement revealed age, stage, grade, extragenital
organ involvement (omentum, bowel, peritoneum), positive cytology, and lymph node
metastasis as significant factors (p<0.05). In the multivariate analysis,
appendiceal involvement was significantly affected by age and omental
involvement. Older age (>50 years) [odds ratio (OR) 2.8; 95% confidence interval
(CI): (1.24-6.37); p=0.014] and presence of omental involvement [OR: 3.2; 95% CI:
(1.22-8.59); p=0.018) seemed to be independent risk factors for appendiceal
involvement in women with EOC. CONCLUSION: Our findings indicate that routine
appendectomy at the time of surgery for apparent early-stage EOC is not
warranted. Nevertheless, the surgeon can take the initiative in regards to
performing appendectomy because the morbidity rates due to this procedure are
negligible. Older age (>50 years) and presence of omental involvement seem to
increase the risk of appendiceal involvement by 2.8 and 3.2 times, respectively.
PMID- 28490414
TI - What is your diagnosis?
PMID- 28490415
TI - Maternal and perinatal characteristics of small-for-gestational-age newborns: Ten
year experience of a single center.
AB - OBJECTIVE: To analyze the maternal and perinatal characteristics of small-for
gestational-age (SGA) newborns compared with appropriate-for-gestational-age
(AGA) newborns in singleton pregnancies managed at our hospital between January
2006 and December 2015. MATERIAL AND METHODS: The study (n=456) and control
(n=4925) groups included pregnancies resulting in SGA and AGA newborns,
respectively. Additionally, two SGA subgroups were defined according to abnormal
(n=34) and normal (n=57) Doppler findings. Maternal demographic features;
intracytoplasmic sperm injection (ICSI) pregnancies; gestational age at delivery;
birth weight; major congenital anomalies, karyotype abnormalities, and genetic
syndromes; maternal and obstetric problems such as hypertensive disorders,
diabetes, oligohydramnios, preterm birth; admission to the neonatal intensive
care unit (NICU), and perinatal mortality were recorded, and the two groups were
compared with respect to these parameters. RESULTS: Mean maternal age, parity,
gestational age at delivery, and birthweight were significantly lower; the
frequencies of ICSI pregnancies, hypertensive disorders, oligohydramnios, preterm
delivery, major congenital anomalies, karyotype abnormalities and genetic
syndromes, admission to the NICU and perinatal mortality were significantly
higher in the study group (p<0.05). None of the study parameters were
significantly different between the two SGA subgroups (p>0.05). CONCLUSION: The
association of SGA with ICSI pregnancies, hypertensive disorders,
oligohydramnios, preterm delivery, congenital/chromosomal anomalies, NICU
admission and perinatal mortality may be important in perinatal care. Clinical
suspicion of SGA necessitates appropriate monitorization and management. Although
obstetric outcomes were not significantly different between the two SGA subgroups
with abnormal and normal Doppler findings in this study, this finding must be
evaluated with caution due to the small sizes.
PMID- 28490416
TI - Development and Assessment of an E-learning Course on Pediatric Cardiology
Basics.
AB - BACKGROUND: Early detection of congenital heart disease is a worldwide problem.
This is more critical in developing countries, where shortage of professional
specialists and structural health care problems are a constant. E-learning has
the potential to improve capacity, by overcoming distance barriers and by its
ability to adapt to the reduced time of health professionals. OBJECTIVE: The
study aimed to develop an e-learning pediatric cardiology basics course and
evaluate its pedagogical impact and user satisfaction. METHODS: The sample
consisted of 62 health professionals, including doctors, nurses, and medical
students, from 20 hospitals linked via a telemedicine network in Northeast
Brazil. The course was developed using Moodle (Modular Object Oriented Dynamic
Learning Environment; Moodle Pty Ltd, Perth, Australia) and contents adapted from
a book on this topic. Pedagogical impact evaluation used a pre and posttest
approach. User satisfaction was evaluated using Wang's questionnaire. RESULTS:
Pedagogical impact results revealed differences in knowledge assessment before
and after the course (Z=-4.788; P<.001). Questionnaire results indicated high
satisfaction values (Mean=87%; SD=12%; minimum=67%; maximum=100%). Course
adherence was high (79%); however, the withdrawal exhibited a value of 39%, with
the highest rate in the early chapters. Knowledge gain revealed significant
differences according to the profession (X22=8.6; P=.01) and specialty (X22=8.4;
P=.04). Time dedication to the course was significantly different between
specialties (X22=8.2; P=.04). CONCLUSIONS: The main contributions of this study
are the creation of an asynchronous e-learning course on Moodle and the
evaluation of its impact, confirming that e-learning is a viable tool to improve
training in neonatal congenital heart diseases.
PMID- 28490417
TI - Accelerating Digital Mental Health Research From Early Design and Creation to
Successful Implementation and Sustainment.
AB - Mental health problems are common and pose a tremendous societal burden in terms
of cost, morbidity, quality of life, and mortality. The great majority of people
experience barriers that prevent access to treatment, aggravated by a lack of
mental health specialists. Digital mental health is potentially useful in meeting
the treatment needs of large numbers of people. A growing number of efficacy
trials have shown strong outcomes for digital mental health treatments. Yet
despite their positive findings, there are very few examples of successful
implementations and many failures. Although the research-to-practice gap is not
unique to digital mental health, the inclusion of technology poses unique
challenges. We outline some of the reasons for this gap and propose a collection
of methods that can result in sustainable digital mental health interventions.
These methods draw from human-computer interaction and implementation science and
are integrated into an Accelerated Creation-to-Sustainment (ACTS) model. The ACTS
model uses an iterative process that includes 2 basic functions (design and
evaluate) across 3 general phases (Create, Trial, and Sustain). The ultimate goal
in using the ACTS model is to produce a functioning technology-enabled service
(TES) that is sustainable in a real-world treatment setting. We emphasize the
importance of the service component because evidence from both research and
practice has suggested that human touch is a critical ingredient in the most
efficacious and used digital mental health treatments. The Create phase results
in at least a minimally viable TES and an implementation blueprint. The Trial
phase requires evaluation of both effectiveness and implementation while allowing
optimization and continuous quality improvement of the TES and implementation
plan. Finally, the Sustainment phase involves the withdrawal of research or donor
support, while leaving a functioning, continuously improving TES in place. The
ACTS model is a step toward bringing implementation and sustainment into the
design and evaluation of TESs, public health into clinical research, research
into clinics, and treatment into the lives of our patients.
PMID- 28490418
TI - Identifying and Understanding the Health Information Experiences and Preferences
of Caregivers of Individuals With Either Traumatic Brain Injury, Spinal Cord
Injury, or Burn Injury: A Qualitative Investigation.
AB - BACKGROUND: In order to meet the challenges of caring for an injured person,
caregivers need access to health information. However, caregivers often feel that
they lack adequate information. Previous studies of caregivers have primarily
focused on either their time and emotional burdens or their health outcomes, but
the information needs of caregivers have not been thoroughly investigated.
OBJECTIVE: The purpose of this investigation was to identify the preferred
sources of health information for caregivers supporting individuals with injuries
and to explore how access to this information could be improved. METHODS: A total
of 32 caregivers participated in semistructured interviews, which were used in
order to develop a more in-depth understanding of these caregivers' information
needs. Digital audio recordings of the interviews were used for analysis
purposes. These audio recordings were analyzed using a thematic analysis or
qualitative content analysis. All of participant's interviews were then coded
using the qualitative analysis program, Nvivo 10 for Mac (QSR International).
RESULTS: The caregivers endorsed similar behaviors and preferences when seeking
and accessing health information. Medical professionals were the preferred source
of information, while ease of access made the Internet the most common avenue to
obtain information. The challenges faced by participants were frequently a result
of limited support. In describing an ideal health system, participants expressed
interest in a comprehensive care website offering support network resources,
instructive services about the injury and caregiving, and injury-specific
materials. CONCLUSIONS: According to the participants, an ideal health
information system would include a comprehensive care website that offered
supportive network resources, instructive services about the injury and
caregiving, and materials specific to the type of patient injury.
PMID- 28490419
TI - Development, Usability, and Efficacy of a Serious Game to Help Patients Learn
About Pain Management After Surgery: An Evaluation Study.
AB - BACKGROUND: Postoperative pain is a persistent problem after surgery and can
delay recovery and develop into chronic pain. Better patient education has been
proposed to improve pain management of patients. Serious games have not been
previously developed to help patients to learn how to manage their postoperative
pain. OBJECTIVE: The aim of this study was to describe the development of a
computer-based game for surgical patients to learn about postoperative pain
management and to evaluate the usability, user experience, and efficacy of the
game. METHODS: A computer game was developed by an interdisciplinary team
following a structured approach. The usability, user experience, and efficacy of
the game were evaluated using self-reported questionnaires (AttrakDiff2,
Postoperative Pain Management Game Survey, Patient Knowledge About Postoperative
Pain Management questionnaire), semi-structured interviews, and direct
observation in one session with 20 participants recruited from the general public
via Facebook (mean age 48 [SD 14]; 11 women). Adjusted Barriers Questionnaire II
and 3 questions on health literacy were used to collect background information.
RESULTS: Theories of self-care and adult learning, evidence for the educational
needs of patients about pain management, and principles of gamification were used
to develop the computer game. Ease of use and usefulness received a median score
between 2.00 (IQR 1.00) and 5.00 (IQR 2.00) (possible scores 0-5; IQR,
interquartile range), and ease of use was further confirmed by observation.
Participants expressed satisfaction with this novel method of learning, despite
some technological challenges. The attributes of the game, measured with
AttrakDiff2, received a median score above 0 in all dimensions; highest for
attraction (median 1.43, IQR 0.93) followed by pragmatic quality (median 1.31,
IQR 1.04), hedonic quality interaction (median 1.00, IQR 1.04), and hedonic
quality stimulation (median 0.57, IQR 0.68). Knowledge of pain medication and
pain management strategies improved after playing the game (P=.001). CONCLUSIONS:
A computer game can be an efficient method of learning about pain management; it
has the potential to improve knowledge and is appreciated by users. To assess the
game's usability and efficacy in the context of preparation for surgery, an
evaluation with a larger sample, including surgical patients and older people, is
required.
PMID- 28490420
TI - Testing the Effectiveness of a Primary Care Intervention to Improve Uptake of
Colorectal Cancer Screening: A Randomized Controlled Trial Protocol.
AB - BACKGROUND: Screening for colorectal cancer (CRC) significantly reduces mortality
associated with this disease. In Australia, the National Bowel Cancer Screening
Program provides regular fecal occult blood tests (FOBT) for those aged 50 to 74
years, however, participation rates in the program have plateaued at 36%. Given
low uptake in the National Bowel Cancer Screening Program, it is necessary to
explore alternate methods to increase CRC screening rates. Primary care is a
promising adjunct setting to test methods to increase CRC screening
participation. Primary care guidelines support the recommendation and provision
of CRC screening to primary care patients. Those in the National Bowel Cancer
Screening Program target age range frequently present to their primary care
provider. OBJECTIVE: This study tests the effect that a multicomponent primary
care-based intervention has on CRC screening uptake when compared to usual care.
METHODS: Primary care patients presenting for an appointment with their primary
care provider complete a touchscreen survey to determine eligibility for the
trial. Those aged 50 to 74 years, at average risk of CRC, with no history of CRC
or inflammatory bowel disease, who have not had an FOBT in the past 2 years or a
colonoscopy in the past 5 years are eligible to participate in the trial. Trial
participants are randomized to the intervention or usual care group by day of
attendance at the practice. The intervention consists of provision of an FOBT,
printed information sheet, and primary care provider endorsement to complete the
FOBT. The usual care group receives no additional care. RESULTS: The primary
outcome is completion of CRC screening 6 weeks after recruitment. The proportion
of patients completing CRC screening will be compared between trial groups using
a logistic regression model. CONCLUSIONS: CRC screening rates in Australia are
suboptimal and interventions to increase screening participation are urgently
required. This protocol describes the process of implementing a multicomponent
intervention designed to increase CRC screening uptake in a primary care setting.
TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry
ACTRN12616001299493;
https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371136&isReview=true
(Archived by WebCite at http://www.webcitation.org/6pL0VYIj6). Universal Trial
Number U1111-1185-6120.
PMID- 28490421
TI - PatientVOICE: Development of a Preparatory, Pre-Chemotherapy Online Communication
Tool for Older Patients With Cancer.
AB - BACKGROUND: Good communication around cancer treatment is essential in helping
patients cope with their disease and related care, especially when this
information is tailored to one's needs. Despite its importance, communication is
often complex, in particular in older patients (aged 65 years or older). In
addition to the age-related deterioration in information and memory processing
older patients experience, communication is also complicated by their required
yet often unmet role of being an active, participatory patient. Older patients
rarely express their informational needs and their contributions to consultations
are often limited. Therefore, older patients with cancer need to be prepared to
participate more actively in their care and treatment. OBJECTIVE: The objective
of this paper was to report the development of PatientVOICE, an online,
preparatory tool with audio facility aimed to enhance the participation of older
patients during educational nursing encounters preceding chemotherapy and to
improve their information recall. METHODS: PatientVOICE was developed by applying
the following 6 steps of the intervention mapping framework that involved both
patients and nurses: (1) needs assessment, (2) specifying determinants and change
objectives, (3) reviewing and selecting theoretical methods and practical
strategies, (4) developing intervention components, (5) designing adoption and
implementation, and (6) making an evaluation plan. RESULTS: A careful execution
of these consecutive steps resulted in the ready-to-use preparatory website.
PatientVOICE provides pre-visit information about chemotherapy (ie, medical
information, side effects, and recommendations of dealing with side effects),
information about the educational nursing visit preceding chemotherapy (ie, aim,
structure, and recommendations for preparation), techniques to improve patients'
communication skills using a question prompt sheet (QPS) and video-modeling
examples showing "best practices", and the opportunity to upload and listen back
to an audio recording of a patient's own nursing visit. CONCLUSIONS: The
development process resulted in PatientVOICE, a multi-component online
intervention targeted to older patients with cancer. PatientVOICE contains
information about the treatment as well as information about the role of the
patient during treatment. Using different methods (QPS and audio facility), we
hope to support these patients during their treatment. In the future, the utility
and usability of this complex intervention will be evaluated in a group of older
patients who receive or have received chemotherapy.
PMID- 28490422
TI - CFTR-mediated anion secretion across intestinal epithelium-like Caco-2 monolayer
under PTH stimulation is dependent on intermediate conductance K+ channels.
AB - Parathyroid hormone (PTH), a pleiotropic hormone that maintains mineral
homeostasis, is also essential for controlling pH balance and ion transport
across renal and intestinal epithelia. Optimization of luminal pH is important
for absorption of trace elements, e.g., calcium and phosphorus. We have
previously demonstrated that PTH rapidly stimulated electrogenic [Formula: see
text] secretion in intestinal epithelial-like Caco-2 monolayers, but the
underlying cellular mechanism, contributions of other ions, particularly Cl- and
K+, and long-lasting responses are not completely understood. Herein, PTH and
forskolin were confirmed to induce anion secretion, which peaked within 1-3 min
(early phase), followed by an abrupt decay and plateau that lasted for 60 min
(late phase). In both early and late phases, apical membrane capacitance was
increased with a decrease in basolateral capacitance after PTH or forskolin
exposure. PTH also induced a transient increase in apical conductance with a long
lasting decrease in basolateral conductance. Anion secretion in both phases was
reduced under [Formula: see text]-free and/or Cl--free conditions or after
exposure to carbonic anhydrase inhibitor (acetazolamide), CFTR inhibitor (CFTRinh
172), Na+/H+ exchanger (NHE)-3 inhibitor (tenapanor), or K+ channel inhibitors
(BaCl2, clotrimazole, and TRAM-34; basolateral side), the latter of which
suggested that PTH action was dependent on basolateral K+ recycling. Furthermore,
early- and late-phase responses to PTH were diminished by inhibitors of PI3K
(wortmannin and LY-294002) and PKA (PKI 14-22). In conclusion, PTH requires NHE3
and basolateral K+ channels to induce [Formula: see text] and Cl- secretion, thus
explaining how PTH regulated luminal pH balance and pH-dependent absorption of
trace minerals.
PMID- 28490423
TI - Declining Trends of Cardiovascular-Renal Complications and Mortality in Type 2
Diabetes: The Hong Kong Diabetes Database.
AB - OBJECTIVE: Nationwide studies on secular trends of diabetes complications are not
available in Asia. We examined changes in risk factor control and incidence of
complications from diabetes and death in a large longitudinal cohort of Chinese
adults with type 2 diabetes in Hong Kong. RESEARCH DESIGN AND METHODS: Between 1
January 2000 and 31 December 2012, 338,908 Chinese adults with type 2 diabetes
underwent metabolic and complication assessment in 16 diabetes centers operated
by Hong Kong Hospital Authority that provided care to a large majority of
diagnosed patients. Patients were followed for incident acute myocardial
infarction (AMI), stroke, end-stage renal disease (ESRD), and death until 31
December 2012. Risk factor levels between enrollment periods were compared.
Incidence of clinical events, stratified by diabetes duration, was examined over
time. RESULTS: Incidence of complications from diabetes and death declined over
the observation period in patients at varying disease duration. Among the high
risk group with diabetes for at least 15 years, crude incidence of AMI decreased
from 8.7 to 5.8, stroke from 13.5 to 10.1, ESRD from 25.8 to 22.5, and death from
29.0 to 26.6 per 1,000 person-year between the periods 2000 to 2002 and 2010 to
2012. Improvements in levels of metabolic risk factors were detected. Proportion
of patients achieving HbA1c <7.0% (53 mmol/mol) was increased from 32.9 to 50.0%,
blood pressure <=130/80 mmHg from 24.7 to 30.7%, and LDL cholesterol <2.6 mmol/L
from 25.8 to 38.1%. CONCLUSIONS: From this territory-wide Hong Kong Diabetes
Database, we observed decreases in incidence of cardiovascular-renal
complications and death and corresponding improvements in risk factor control
over a 13-year period.
PMID- 28490425
TI - Sixty seconds on . . . #publicduty.
PMID- 28490426
TI - Health care needs and use of health care services among newly arrived Syrian
refugees: a cross-sectional study.
AB - BACKGROUND: Canada welcomed 33 723 Syrian refugees between November 2015 and
November 2016. This paper reports the results of a rapid assessment of health
care needs and use of health care services among newly arrived Syrian refugees in
Toronto. METHODS: A cross-sectional study was conducted in Toronto among Syrian
refugees aged 18 years or more who had been in Canada for 12 months or less.
Participants were recruited initially through distribution of flyers in hotels
and through direct referrals and communication with community and settlement
agency partners, and then through snowball sampling. We collected
sociodemographic information and data on self-perceived physical health and
mental health, unmet health care needs and use of health care services. RESULTS:
A total of 400 Syrian refugees (221 women [55.2%] and 179 men [44.8%]) were
enrolled. Of the 400, 209 (52.2%) were privately sponsored refugees, 177 (44.2%)
were government-assisted refugees, and 12 (3.0%) were refugees under the Blended
Visa Office-Referred Program. They reported high levels of self-perceived
physical and mental health. Over 90% of the sample saw a doctor in their first
year in Canada, and 79.8% had a family doctor they saw regularly. However, almost
half (49.0%) of the respondents reported unmet health care needs, with the 3 most
common reasons reported being long wait times, costs associated with services and
lack of time to seek health care services. INTERPRETATION: Many factors may
explain our respondents' high levels of self-perceived physical and mental health
during the first year of resettlement, including initial resettlement support and
eligibility for health care under the Interim Federal Health Program. However,
newly arrived Syrian refugees report unmet health care needs, which necessitates
more comprehensive care and management beyond the initial resettlement support.
PMID- 28490424
TI - Waning Immunity and Microbial Vaccines-Workshop of the National Institute of
Allergy and Infectious Diseases.
AB - Since the middle of the 20th century, vaccines have made a significant public
health impact by controlling infectious diseases globally. Although long-term
protection has been achieved with some vaccines, immunity wanes over time with
others, resulting in outbreaks or epidemics of infectious diseases. Long-term
protection against infectious agents that have a complex life cycle and antigenic
variation remains a key challenge. Novel strategies to characterize the short-
and long-term immune responses to vaccines and to induce immune responses that
mimic natural infection have recently emerged. New technologies and approaches in
vaccinology, such as adjuvants, delivery systems, and antigen formulations, have
the potential to elicit more durable protection and fewer adverse reactions;
together with in vitro systems, these technologies have the capacity to model and
accelerate vaccine development. The National Institute of Allergy and Infectious
Diseases (NIAID) held a workshop on 19 September 2016 that focused on waning
immunity to selected vaccines (for Bordetella pertussis, Salmonella enterica
serovar Typhi, Neisseria meningitidis, influenza, mumps, and malaria), with an
emphasis on identifying knowledge gaps, future research needs, and how this
information can inform development of more effective vaccines for infectious
diseases.
PMID- 28490427
TI - Effect of acute intraocular pressure elevation on the minimum rim width in
normal, ocular hypertensive and glaucoma eyes.
AB - BACKGROUND: To estimate and compare changes in the Bruch's membrane opening
minimum rim width (BMO-MRW) and area in normal, ocular hypertensive and glaucoma
eyes following acute elevations in intraocular pressure (IOP). METHODS: The optic
nerve heads (ONHs) of 104 subjects (31 normals, 20 ocular hypertension (OHT) and
53 with primary glaucoma) were imaged using Spectral-domain optical coherence
tomography (OCT; Spectralis, Heidelberg Engineering, Germany). IOP was raised
twice by applying a force (0.64 n then 0.9 n) to the anterior sclera using an
ophthalmo-dynamometer. After each IOP increment, IOP was held constant, measured
with a Tonopen (AVIA applanation tonometer, Reichert, Depew, New York, USA), and
ONH was rescanned with OCT. In each OCT volume, BMO-MRW and area were calculated
and at each IOP increment. RESULTS: The baseline MRW was significantly smaller in
glaucoma subjects (174.3+/-54.3 um) compared with normal (287.4+/-42.2 um,
p<0.001) and OHT subjects (255.4+/-45.3 um, p<0.001). MRW of glaucoma subjects
was significantly thinner at the first and second IOP elevations than that at
baseline (both p<0.01), but no significant change was noted in normal and OHT
subjects. There was no significant change of BMO area at acute IOP elevations
from baseline in all diagnoses (all p>0.05). CONCLUSION: Acute IOP elevation
leads to compression of the nerve fibre layers of neuroretinal rim in glaucoma
subjects only without changing ONH size. This suggests that the neural and
connective tissues at ONH level in glaucoma subjects are more susceptible to
acute IOP episodes than OHT or normal controls.
PMID- 28490428
TI - Famine, conflict, and political indifference.
PMID- 28490429
TI - Closing the Care Gap: A Primer on Quality Improvement for Heart Failure
Clinicians.
AB - Quality improvement (QI) initiatives have become an integral part of patient
centered care. In this primer, we outline 6 steps for initiating, implementing,
and monitoring improvement in heart failure care. These steps include
acknowledging that improvement is needed and setting a culture for improvement;
forming a QI team; understanding the local problem; generating improvement
strategies that will fit with the local problem; monitoring; testing; and
refining improvements, analysis of data, and interpretation of run charts. This
primer provides tools and resources for clinicians who want to learn how to
perform QI specifically in the field of heart failure. We will illustrate the
application of these steps using a hypothetical example for a congestive heart
failure postdischarge clinic.
PMID- 28490430
TI - Percutaneous Mitral Valve Edge-to-Edge Repair Assisted by Hemodynamic Support
Devices: A Case Series of Bailout Procedures.
PMID- 28490431
TI - Arthroscopic surgery for degenerative knee arthritis and meniscal tears: a
clinical practice guideline.
PMID- 28490435
TI - Home Dialysis in the Prospective Payment System Era.
AB - The ESRD Prospective Payment System introduced two incentives to increase home
dialysis use: bundling injectable medications into a single payment for treatment
and paying for home dialysis training. We evaluated the effects of the ESRD
Prospective Payment System on home dialysis use by patients starting dialysis in
the United States from January 1, 2006 to August 31, 2013. We analyzed data on
dialysis modality, insurance type, and comorbidities from the United States Renal
Data System. We estimated the effect of the policy on home dialysis use with
multivariable logistic regression and compared the effect on Medicare Parts A/B
beneficiaries with the effect on patients with other types of insurance. The ESRD
Prospective Payment System associated with a 5.0% (95% confidence interval [95%
CI], 4.0% to 6.0%) increase in home dialysis use by the end of the study period.
Home dialysis use increased by 5.8% (95% CI, 4.3% to 6.9%) among Medicare
beneficiaries and 4.1% (95% CI, 2.3% to 5.4%) among patients covered by other
forms of health insurance. The difference between these groups was not
statistically significant (1.8%; 95% CI, -0.2% to 3.8%). Conversely, in both
populations, the training add-on did not associate with increases in home
dialysis use beyond the effect of the policy. The ESRD Prospective Payment System
bundling, but not the training add-on, associated with substantial increases in
home dialysis, which were identical for both Medicare and non-Medicare patients.
These spill-over effects suggest that major payment changes in Medicare can
affect all patients with ESRD.
PMID- 28490433
TI - Peripheral Blood Cytokine Levels After Acute Myocardial Infarction: IL-1beta- and
IL-6-Related Impairment of Bone Marrow Function.
AB - RATIONALE: Intracoronary infusion of bone marrow (BM) mononuclear cells after
acute myocardial infarction (AMI) has led to limited improvement in left
ventricular function. Although experimental AMI models have implicated cytokine
related impairment of progenitor cell function, this response has not been
investigated in humans. OBJECTIVE: To test the hypothesis that peripheral blood
(PB) cytokines predict BM endothelial progenitor cell colony outgrowth and
cardiac function after AMI. METHODS AND RESULTS: BM and PB samples were collected
from 87 participants 14 to 21 days after AMI and BM from healthy donors was used
as a reference. Correlations between cytokine concentrations and cell phenotypes,
cell functions, and post-AMI cardiac function were determined. PB interleukin-6
(IL-6) negatively correlated with endothelial colony-forming cell colony maximum
in the BM of patients with AMI (estimate+/-SE, -0.13+/-0.05; P=0.007). BM from
healthy individuals showed a dose-dependent decrease in endothelial colony
forming cell colony outgrowth in the presence of exogenous IL-1beta or IL-6
(P<0.05). Blocking the IL-1R or IL-6R reversed cytokine impairment. In AMI study
participants, the angiogenic cytokine platelet-derived growth factor BB
glycoprotein correlated positively with BM-derived colony-forming unit
endothelial colony maximum (estimate+/-SE, 0.01+/-0.002; P<0.001), multipotent
mesenchymal stromal cell colony maximum (estimate+/-SE, 0.01+/-0.002; P=0.002) in
BM, and mesenchymal stromal cell colony maximum in PB (estimate+/-SE, 0.02+/
0.005; P<0.001). CONCLUSIONS: Two weeks after AMI, increased PB platelet-derived
growth factor BB glycoprotein was associated with increased BM function, whereas
increased IL-6 was associated with BM impairment. Validation studies confirmed
inflammatory cytokine impairment of BM that could be reversed by blocking IL-1R
or IL-6R. Together, these studies suggest that blocking IL-1 or IL-6 receptors
may improve the regenerative capacity of BM cells after AMI. CLINICAL TRIAL
REGISTRATIONS: URL: http://www.clinicaltrials.gov. Unique identifier:
NCT00684060.
PMID- 28490436
TI - Longitudinal Associations among Renal Urea Clearance-Corrected Normalized Protein
Catabolic Rate, Serum Albumin, and Mortality in Patients on Hemodialysis.
AB - BACKGROUND AND OBJECTIVES: There are inconsistent reports on the association of
dietary protein intake with serum albumin and outcomes among patients on
hemodialysis. Using a new normalized protein catabolic rate (nPCR) variable
accounting for residual renal urea clearance, we hypothesized that higher
baseline nPCR and rise in nPCR would be associated with higher serum albumin and
better survival among incident hemodialysis patients. DESIGN, SETTING,
PARTICIPANTS, & MEASUREMENTS: Among 36,757 incident hemodialysis patients in a
large United States dialysis organization, we examined baseline and change in
renal urea clearance-corrected nPCR as a protein intake surrogate and modeled
their associations with serum albumin and mortality over 5 years (1/2007
12/2011). RESULTS: Median nPCRs with and without accounting for renal urea
clearance at baseline were 0.94 and 0.78 g/kg per day, respectively (median
within-patient difference, 0.14 [interquartile range, 0.07-0.23] g/kg per day).
During a median follow-up period of 1.4 years, 8481 deaths were observed.
Baseline renal urea clearance-corrected nPCR was associated with higher serum
albumin and lower mortality in the fully adjusted model (Ptrend<0.001). Among
13,895 patients with available data, greater rise in renal urea clearance
corrected nPCR during the first 6 months was also associated with attaining high
serum albumin (>=3.8 g/dl) and lower mortality (Ptrend<0.001); compared with the
reference group (a change of 0.1-0.2 g/kg per day), odds and hazard ratios were
0.53 (95% confidence interval, 0.44 to 0.63) and 1.32 (95% confidence interval,
1.14 to 1.54), respectively, among patients with a change of <-0.2 g/kg per day
and 1.62 (95% confidence interval, 1.35 to 1.96) and 0.76 (95% confidence
interval, 0.64 to 0.90), respectively, among those with a change of >=0.5 g/kg
per day. Within a given category of nPCR without accounting for renal urea
clearance, higher levels of renal urea clearance-corrected nPCR consistently
showed lower mortality risk. CONCLUSIONS: Among incident hemodialysis patients,
higher dietary protein intake represented by nPCR and its changes over time
appear to be associated with increased serum albumin levels and greater survival.
nPCR may be underestimated when not accounting for renal urea clearance. Compared
with the conventional nPCR, renal urea clearance-corrected nPCR may be a better
marker of mortality.
PMID- 28490437
TI - High-throughput CRISPRi phenotyping identifies new essential genes in
Streptococcus pneumoniae.
AB - Genome-wide screens have discovered a large set of essential genes in the
opportunistic human pathogen Streptococcus pneumoniae However, the functions of
many essential genes are still unknown, hampering vaccine development and drug
discovery. Based on results from transposon sequencing (Tn-seq), we refined the
list of essential genes in S. pneumoniae serotype 2 strain D39. Next, we created
a knockdown library targeting 348 potentially essential genes by CRISPR
interference (CRISPRi) and show a growth phenotype for 254 of them (73%). Using
high-content microscopy screening, we searched for essential genes of unknown
function with clear phenotypes in cell morphology upon CRISPRi-based depletion.
We show that SPD_1416 and SPD_1417 (renamed to MurT and GatD, respectively) are
essential for peptidoglycan synthesis, and that SPD_1198 and SPD_1197 (renamed to
TarP and TarQ, respectively) are responsible for the polymerization of teichoic
acid (TA) precursors. This knowledge enabled us to reconstruct the unique
pneumococcal TA biosynthetic pathway. CRISPRi was also employed to unravel the
role of the essential Clp-proteolytic system in regulation of competence
development, and we show that ClpX is the essential ATPase responsible for ClpP
dependent repression of competence. The CRISPRi library provides a valuable tool
for characterization of pneumococcal genes and pathways and revealed several
promising antibiotic targets.
PMID- 28490439
TI - Skeletal muscle metabolism during prolonged exercise in Pompe disease.
AB - OBJECTIVE: Pompe disease (glycogenosis type II) is caused by lysosomal alpha
glucosidase deficiency, which leads to a block in intra-lysosomal glycogen
breakdown. In spite of enzyme replacement therapy, Pompe disease continues to be
a progressive metabolic myopathy. Considering the health benefits of exercise, it
is important in Pompe disease to acquire more information about muscle substrate
use during exercise. METHODS: Seven adults with Pompe disease were matched to a
healthy control group (1:1). We determined (1) peak oxidative capacity (VO2peak)
and (2) carbohydrate and fatty acid metabolism during submaximal exercise (33 W)
for 1 h, using cycle-ergometer exercise, indirect calorimetry and stable
isotopes. RESULTS: In the patients, VO2peak was less than half of average control
values; mean difference -1659 mL/min (CI: -2450 to -867, P = 0.001). However, the
respiratory exchange ratio increased to >1.0 and lactate levels rose 5-fold in
the patients, indicating significant glycolytic flux. In line with this, during
submaximal exercise, the rates of oxidation (ROX) of carbohydrates and palmitate
were similar between patients and controls (mean difference 0.226 g/min (CI:
0.611 to -0.078, P = 0.318) and mean difference 0.016 umol/kg/min (CI: 1.287 to
1.255, P = 0.710), respectively). CONCLUSION: Reflecting muscle weakness and
wasting, Pompe disease is associated with markedly reduced maximal exercise
capacity. However, glycogenolysis is not impaired in exercise. Unlike in other
metabolic myopathies, skeletal muscle substrate use during exercise is normal in
Pompe disease rendering exercise less complicated for e.g. medical or
recreational purposes.
PMID- 28490438
TI - Inefficient recruitment of kinesin-1 to melanosomes precludes it from
facilitating their transport.
AB - Microtubules and F-actin, and their associated motor proteins, are considered to
play complementary roles in long- and short-range organelle transport. However,
there is growing appreciation that myosin/F-actin networks can drive long-range
transport. In melanocytes, myosin-Va and kinesin-1 have both been proposed as
long-range centrifugal transporters moving melanosomes into the peripheral
dendrites. Here, we investigated the role of kinesin-1 heavy chain (Kif5b) and
its suggested targeting factor Rab1a in transport. We performed confocal
microscopy and subcellular fractionation, but did not detect Kif5b or Rab1a on
melanosomes. Meanwhile functional studies, using siRNA knockdown and dominant
negative mutants, did not support a role for Kif5b or Rab1a in melanosome
transport. To probe the potential of Kif5b to function in transport, we generated
fusion proteins that target active Kif5b to melanosomes and tested their ability
to rescue perinuclear clustering in myosin-Va-deficient cells. Expression of
these chimeras, but not full-length Kif5b, dispersed melanosomes with similar
efficiency to myosin-Va. Our data indicate that kinesin and microtubules can
compensate for defects in myosin-Va and actin-based transport in mammals, but
that endogenous Kif5b does not have an important role in transport of melanocytes
due to its inefficient recruitment to melanosomes.
PMID- 28490442
TI - Dexamethasone and sex regulate placental glucocorticoid receptor isoforms in
mice.
AB - Maternal dexamethasone exposure in the mouse impairs placental development and
programs adult disease in a sexually dimorphic manner. Glucocorticoids bind to
different glucocorticoid receptor (GR) isoforms to regulate gene transcription
and cellular signaling. We hypothesized that sexually dimorphic placental
responses to glucocorticoids are due to differences in GR isoforms present in the
placenta. Pregnant C57Bl6 mice were exposed to saline or dexamethasone from E12.5
until E14.5 (1 ug/kg/h) before the collection of placentae. Cytoplasmic and
nuclear protein fractions were extracted from placentae of male and female
fetuses for Western blot analysis of GR isoforms. Eight known isoforms of the GR
were detected in the mouse placenta including the translational isoforms GRalpha
A, B, C and D1-3 and the splice variants GRA and GRP. The expression of GRA, GRP
and each of the GRalpha isoforms were altered by dexamethasone in relation to
fetal sex and cellular location. Placentae of female fetuses had higher GRalpha-A
and GRP expression in the cytoplasm than males, and GRalpha-C was more highly
expressed in the nucleus of females than that in males. Dexamethasone
significantly increased the cytoplasmic expression of GRalpha-A, but reduced the
expression of GRalpha-C in placentae of males. Dexamethasone increased the
expression of the GRalpha-C-regulated genes Sgk1 and Bcl2l11, particularly in
females. The cleaved caspase-3 staining in placental sections indicated GRalpha-C
may mediate sex differences in dexamethasone-induced apoptosis. These findings
may underlie the sex-specific placental adaptations that regulate different
growth profiles in males and females and different risks for programmed disease
outcomes in offspring.
PMID- 28490440
TI - Human memory CD8 T cell effector potential is epigenetically preserved during in
vivo homeostasis.
AB - Antigen-independent homeostasis of memory CD8 T cells is vital for sustaining
long-lived T cell-mediated immunity. In this study, we report that maintenance of
human memory CD8 T cell effector potential during in vitro and in vivo
homeostatic proliferation is coupled to preservation of acquired DNA methylation
programs. Whole-genome bisulfite sequencing of primary human naive, short-lived
effector memory (TEM), and longer-lived central memory (TCM) and stem cell memory
(TSCM) CD8 T cells identified effector molecules with demethylated promoters and
poised for expression. Effector-loci demethylation was heritably preserved during
IL-7- and IL-15-mediated in vitro cell proliferation. Conversely, cytokine-driven
proliferation of TCM and TSCM memory cells resulted in phenotypic conversion into
TEM cells and was coupled to increased methylation of the CCR7 and Tcf7 loci.
Furthermore, haploidentical donor memory CD8 T cells undergoing in vivo
proliferation in lymphodepleted recipients also maintained their effector
associated demethylated status but acquired TEM-associated programs. These data
demonstrate that effector-associated epigenetic programs are preserved during
cytokine-driven subset interconversion of human memory CD8 T cells.
PMID- 28490441
TI - PD-1 regulates KLRG1+ group 2 innate lymphoid cells.
AB - Group 2 innate lymphoid cells (ILC-2s) regulate immune responses to pathogens and
maintain tissue homeostasis in response to cytokines. Positive regulation of ILC
2s through ICOS has been recently elucidated. We demonstrate here that PD-1 is an
important negative regulator of KLRG1+ ILC-2 function in both mice and humans.
Increase in KLRG1+ ILC-2 cell numbers was attributed to an intrinsic defect in PD
1 signaling, which resulted in enhanced STAT5 activation. During Nippostrongylus
brasiliensis infection, a significant expansion of KLRG1+ ILC-2 subsets occurred
in Pdcd1-/- mice and, upon adoptive transfer, Pdcd1-/- KLRG1+ ILC-2s
significantly reduced worm burden. Furthermore, blocking PD-1 with an antibody
increased KLRG1+ ILC-2 cell number and reduced disease burden. Therefore, PD-1 is
required for maintaining the number, and hence function, of KLRG1+ ILC-2s.
PMID- 28490443
TI - Peripheral insulin resistance in ILK-depleted mice by reduction of GLUT4
expression.
AB - The development of insulin resistance is characterized by the impairment of
glucose uptake mediated by glucose transporter 4 (GLUT4). Extracellular matrix
changes are induced when the metabolic dysregulation is sustained. The present
work was devoted to analyze the possible link between the extracellular-to
intracellular mediator integrin-linked kinase (ILK) and the peripheral tissue
modification that leads to glucose homeostasis impairment. Mice with general
depletion of ILK in adulthood (cKD-ILK) maintained in a chow diet exhibited
increased glycemia and insulinemia concurrently with a reduction of the
expression and membrane presence of GLUT4 in the insulin-sensitive peripheral
tissues compared with their wild-type littermates (WT). Tolerance tests and
insulin sensitivity indexes confirmed the insulin resistance in cKD-ILK,
suggesting a similar stage to prediabetes in humans. Under randomly fed
conditions, no differences between cKD-ILK and WT were observed in the expression
of insulin receptor (IR-B) and its substrate IRS-1 expressions. The IR-B isoform
phosphorylated at tyrosines 1150/1151 was increased, but the AKT phosphorylation
in serine 473 was reduced in cKD-ILK tissues. Similarly, ILK-blocked myotubes
reduced their GLUT4 promoter activity and GLUT4 expression levels. On the other
hand, the glucose uptake capacity in response to exogenous insulin was impaired
when ILK was blocked in vivo and in vitro, although IR/IRS/AKT phosphorylation
states were increased but not different between groups. We conclude that ILK
depletion modifies the transcription of GLUT4, which results in reduced
peripheral insulin sensitivity and glucose uptake, suggesting ILK as a molecular
target and a prognostic biomarker of insulin resistance.
PMID- 28490444
TI - Inhibiting glucosylceramide synthase exacerbates cisplatin-induced acute kidney
injury.
AB - Acute kidney injury (AKI), resulting from chemotherapeutic agents such as
cisplatin, remains an obstacle in the treatment of cancer. Cisplatin-induced AKI
involves apoptotic and necrotic cell death, pathways regulated by sphingolipids
such as ceramide and glucosylceramide. Results from this study indicate that
C57BL/6J mice treated with cisplatin had increased ceramide and hexosylceramide
levels in the renal cortex 72 h following cisplatin treatment. Pretreatment of
mice with inhibitors of acid sphingomyelinase and de novo ceramide synthesis
(amitriptyline and myriocin, respectively) prevented accumulation of ceramides
and hexosylceramide in the renal cortex and protected from cisplatin-induced AKI.
To determine the role of ceramide metabolism to hexosylceramides in kidney
injury, we treated mice with a potent and highly specific inhibitor of
glucosylceramide synthase, the enzyme responsible for catalyzing the
glycosylation of ceramides to form glucosylceramides. Inhibition of
glucosylceramide synthase attenuated the accumulation of the hexosylceramides and
exacerbated ceramide accumulation in the renal cortex following treatment of mice
with cisplatin. Increasing ceramides and decreasing glucosylceramides in the
renal cortex sensitized mice to cisplatin-induced AKI according to markers of
kidney function, kidney injury, inflammation, cell stress, and apoptosis. Under
conditions of high ceramide generation, data suggest that metabolism of ceramides
to glucosylceramides buffers kidney ceramides and helps attenuate kidney injury.
Dupre, T. V., M. A. Doll, P. P. Shah, C. N. Sharp, D. Siow, J. Megyesi, J.
Shayman, A. Bielawska, J. Bielawski, L. J. Beverly, M. Hernandez-Corbacho, C. J.
Clarke, A. J. Snider, R. G. Schnellmann, L. M. Obeid, Y. A. Hannun, and L. J.
Siskind. Inhibiting glucosylceramide synthase exacerbates cisplatin-induced acute
kidney injury. J. Lipid Res 2017. 58: 1439-1452.
PMID- 28490446
TI - Tolerance to herbivory and the resource availability hypothesis.
AB - The resource availability hypothesis (RAH), the most successful theory explaining
plant defence patterns, predicts that defence investment is related to the
relative growth rate (RGR) of plant species, which is associated with habitat
quality. Thus, fast-growing species should show lower resistance than slow
growing species, which would lead fast growers to sustain higher herbivory rates,
but the fitness consequences of herbivory would be greater for slow growers. The
latter is often assumed but rarely tested. In a temperate rainforest, we tested
the expected pattern of tolerance to herbivory derived from the RAH: that fast
growing species should be more tolerant than slow-growing species. We also
evaluated whether other plant features covary with RGR (leaf lifespan, shade
tolerance and leaf toughness) and thus could also contribute to the patterns of
tolerance to herbivory. As expected, seedlings from tree species with higher RGR
showed greater tolerance to herbivory. Among the three plant features included,
only leaf lifespan showed a significant association with RGR, but RGR was the
best predictor of tolerance. We argue that plant tolerance to herbivory must be
evaluated to properly verify the assumptions of the RAH.
PMID- 28490445
TI - Serological Epithelial Component Proteins Identify Intestinal Complications in
Crohn's Disease.
AB - Crohn's Disease (CD) is a relapsing inflammation of the gastrointestinal tract
that affects a young working age population and is increasing in developing
countries. Half of all sufferers will experience stricturing or fistulizing
intestinal complications that require extensive surgical interventions and
neither genes nor clinical risk factors can predict this debilitating natural
history. We applied discovery and verification phase studies as part of an NCI
FDA modeled biomarker pipeline to identify differences in the low-mass (<25kDa)
blood-serum proteome between CD behavioral phenotypes. A significant enrichment
of epithelial component proteins was identified in CD patients with intestinal
complications using quantitative proteomic profiling with label-free Liquid
Chromatography-Tandem Mass Spectrometry (LC-MS/MS). DAVID 6.7 (NIH) was used for
functional annotation analysis of detected proteins and immunoblotting and
multiple reaction monitoring (MRM) to verify a priori findings in a secondary
independent cohort of complicated CD (CCD), uncomplicated inflammatory CD (ICD),
Th1/17 pathway inflammation controls (rheumatoid arthritis), inflammatory bowel
disease controls (ulcerative colitis), and healthy controls. Seventy-six high
confidence serum proteins were modulated in CCD versus ICD by LC-MS/MS (p < 0.05,
FDR q<0.01), annotating to pathways of epithelial barrier homeostasis (p < 0.01).
In verification phase, a putative serology panel developed from discovery
proteomics data consisting of desmoglein-1, desmoplakin, and fatty acid-binding
protein 5 (FABP5) distinguished CCD from all other groups (p = 0.041) and
discriminated complication in CD (70% sensitivity and 72.5% specificity at score
>=1.907, AUC = 0.777, p = 0.007). An MRM assay secondarily confirmed increased
FABP5 levels in CCD (p < 0.001). In a longitudinal subanalysis-cohort, FABP5
levels were stable over a two-month period with no behavioral changes (p =
0.099). These studies along the biomarker development pipeline provide
substantial proof-of-principle that a blood test can be developed specific to
transmural intestinal injury. Data are available via the PRIDE proteomics data
repository under identifier PXD001821 and PeptideAtlas with identifier PASS00661.
PMID- 28490447
TI - Plant spines deter herbivory by restricting caterpillar movement.
AB - The spines of flowering plants are thought to function primarily in defence
against mammalian herbivores; however, we previously reported that feeding by
Manduca sexta caterpillars on the leaves of horsenettle plants (Solanum
carolinense) induces increased development of internode spines on new growth. To
determine whether and how spines impact caterpillar feeding, we conducted assays
with three Solanaceous plant species that vary in spine numbers (S. carolinense,
S. atropurpureum and S. aethiopicum) and also manipulated spine numbers within
each species. We found that M. sexta caterpillars located experimentally isolated
target leaves much more quickly on plants with experimentally removed spines
compared with plants with intact spines. Moreover, it took caterpillars longer to
defoliate species with relatively high spine numbers (S. carolinense and
particularly Satropurpureum) compared with S. aethiopicum, which has fewer
spines. These findings suggest that spines may play a significant role in defence
against insect herbivores by restricting herbivore movement and increasing the
time taken to access feeding sites, with possible consequences including longer
developmental periods and increased vulnerability or apparency to predators.
PMID- 28490448
TI - Intermittent hypoxia training blunts cerebrocortical presenilin 1 overexpression
and amyloid-beta accumulation in ethanol-withdrawn rats.
AB - Abrupt cessation of chronic alcohol consumption triggers signaling cascades that
harm vulnerable brain regions and produce neurobehavioral deficits. We have
demonstrated that a program of intermittent, normobaric hypoxia training (IHT) in
rats prevents brain damage and neurobehavioral impairment resulting from abrupt
ethanol withdrawal (EW). Moreover, EW induced expression of stress-activated
protein kinase p38 and presenilin 1 (PS1), the catalytic subunit of gamma
secretase that produces the neurotoxic amyloid-beta (Abeta) peptides Abeta40 and
Abeta42. We tested the hypotheses that 1) IHT limits EW-induced activation of the
p38-PS1 axis, thereby attenuating gamma-secretase activation and Abeta
accumulation, and 2) EW disables heat shock protein 25 (HSP25), a p38 substrate,
molecular chaperone, and antioxidant, and provokes protein carbonylation in a
manner suppressed by IHT. Adult male rats completed two cycles of a 4-wk ethanol
diet (6.5% wt/vol) and a 3-wk EW or an isocaloric, dextrin-based control diet. A
20-day IHT program (5-8 daily cycles of 5-10 min of 9.5-10% fractional inspired
O2 + 4 min of 21% fractional inspired O2) was administered during the first EW
phase. After the second EW phase, the brain was excised and the prefrontal cortex
extracted. PS1, phosphorylated p38 (p-p38), and HSP25 were analyzed by
immunoblot, PS1 messenger RNA by quantitative polymerase chain reaction, protein
carbonyl content by spectrometry, and Abeta40 and Abeta42 contents by enzyme
linked immunosorbent assay. IHT attenuated the EW-associated increases in PS1, p
p38, Abeta40, Abeta42, and protein carbonyl contents, but not that of PS1
messenger RNA, while preserving functionally competent HSP25 dimers in EW rats.
Collectively, these findings suggest that IHT may attenuate EW-induced gamma
secretase overactivation by suppressing activation of the p38-PS1 axis and by
preventing oxidative protein damage.
PMID- 28490450
TI - Sedentary conditions and enhanced responses to GABA in the RVLM: role of the
contralateral RVLM.
AB - A sedentary lifestyle is a major risk factor for cardiovascular disease, and both
conditions are associated with overactivity of the sympathetic nervous system.
Ongoing discharge of sympathetic nerves is regulated by the rostral ventrolateral
medulla (RVLM), which in turn is modulated by the primary excitatory and
inhibitory neurotransmitters glutamate and gamma-amino-butyric acid (GABA),
respectively. We reported previously that sedentary conditions enhance GABAergic
modulation of sympathoexcitation in the RVLM, despite overall increased
sympathoexcitation. Thus the purpose of this study was to test the hypothesis
that sedentary conditions increase responsiveness to GABA in RVLM. Male Sprague
Dawley rats performed either chronic wheeling running or remained sedentary for
12-15 wk. Animals were instrumented to perform RVLM microinjections under Inactin
anesthesia while mean arterial pressure (MAP) and splanchnic sympathetic nerve
activity (SSNA) were recorded. Unilateral microinjections of GABA (30 nl, 0.3-600
mM) into the RVLM produced dose-dependent decreases in MAP and SSNA; however, no
group differences were observed. Inhibition of the contralateral RVLM (muscimol,
2 mM, 90 nl) caused decreases in MAP and SSNA that were not different between
groups but enhanced decreases in SSNA to GABA in sedentary rats only. In
sinoaortic denervated rats, GABA microinjections before or after inhibition of
the contralateral RVLM caused decreases in MAP and SSNA that were not different
between groups. Our results suggest that the contralateral RVLM plays an
important role in buffering responses to inhibition of the ipsilateral RVLM under
sedentary but not physically active conditions. Based on these studies and
others, sedentary conditions appear to enhance both sympathoinhibitory and
sympathoexcitatory mechanisms in the RVLM. Enhanced sympathoinhibition may act to
reduce already elevated sympathetic nervous system activity following sedentary
conditions.
PMID- 28490449
TI - Enhanced insulin secretion and insulin sensitivity in young lambs with placental
insufficiency-induced intrauterine growth restriction.
AB - Intrauterine growth restriction (IUGR) is associated with persistent metabolic
complications, but information is limited for IUGR infants. We determined glucose
stimulated insulin secretion (GSIS) and insulin sensitivity in young lambs with
placental insufficiency-induced IUGR. Lambs with hyperthermia-induced IUGR (n =
7) were compared with control lambs (n = 8). GSIS was measured at 8 +/- 1 days of
age, and at 15 +/- 1 days, body weight-specific glucose utilization rates were
measured with radiolabeled d-glucose during a hyperinsulinemic-euglycemic clamp
(HEC). IUGR lambs weighed 23% less (P < 0.05) than controls at birth. Fasting
plasma glucose and insulin concentrations were not different between IUGR and
controls for either study. First-phase insulin secretion was enhanced 2.3-fold in
IUGR lambs compared with controls. However, second-phase insulin concentrations,
glucose-potentiated arginine-stimulated insulin secretion, and beta-cell mass
were not different, indicating that IUGR beta-cells have an intrinsic enhancement
in acute GSIS. Compared with controls, IUGR lambs had higher body weight-specific
glucose utilization rates and greater insulin sensitivity at fasting (1.6-fold)
and hyperinsulinemic periods (2.4-fold). Improved insulin sensitivity for glucose
utilization was not due to differences in skeletal muscle insulin receptor and
glucose transporters 1 and 4 concentrations. Plasma lactate concentrations during
HEC were elevated in IUGR lambs compared with controls, but no differences were
found for glycogen content or citrate synthase activity in liver and muscle.
Greater insulin sensitivity for glucose utilization and enhanced acute GSIS in
young lambs are predicted from fetal studies but may promote conditions that
exaggerate glucose disposal and lead to episodes of hypoglycemia in IUGR infants.
PMID- 28490451
TI - Evidence for intraventricular secretion of angiotensinogen and angiotensin by the
subfornical organ using transgenic mice.
AB - Direct intracerebroventricular injection of angiotensin II (ANG II) causes
increases in blood pressure and salt and water intake, presumably mimicking an
effect mediated by an endogenous mechanism. The subfornical organ (SFO) is a
potential source of cerebrospinal fluid (CSF), ANG I, and ANG II, and thus we
hypothesized that the SFO has a secretory function. Endogenous levels of
angiotensinogen (AGT) and renin are very low in the brain. We therefore examined
the immunohistochemical localization of angiotensin peptides and AGT in the SFO,
and AGT in the CSF in two transgenic models that overexpress either human AGT (A+
mice), or both human AGT (hAGT) and human renin (SRA mice) in the brain.
Measurements were made at baseline and following volumetric depletion of CSF.
Ultrastructural analysis with immunoelectron microscopy revealed that
superficially located ANG I/ANG II and AGT immunoreactive cells in the SFO were
vacuolated and opened directly into the ventricle. Withdrawal of CSF produced an
increase in AGT in the CSF that was accompanied by a large decline in AGT
immunoreactivity within SFO cells. Our data provide support for the hypothesis
that the SFO is a secretory organ that releases AGT and possibly ANG I/ANG II
into the ventricle at least under conditions when genes that control the renin
angiotensin system are overexpressed in mice.
PMID- 28490453
TI - Joanna Cannon: Psychiatry and paperbacks.
PMID- 28490452
TI - Role of endothelial nitric oxide in control of peripheral vascular conductance
during muscle metaboreflex activation.
AB - The muscle metaboreflex is a powerful pressor reflex induced by the activation of
chemically sensitive muscle afferents as a result of metabolite accumulation.
During submaximal dynamic exercise, the rise in arterial pressure is primarily
due to increases in cardiac output, since there is little systemic
vasoconstriction. Indeed, in normal animals, we have often shown a small, but
significant, peripheral vasodilation during metaboreflex activation, which is
mediated, at least in part, by release of epinephrine and activation of vascular
beta2-receptors. We tested whether this vasodilation is in part due to increased
release of nitric oxide caused by the rise in cardiac output eliciting
endothelium-dependent flow-mediated vasodilation. The muscle metaboreflex was
activated via graded reductions in hindlimb blood flow during mild exercise with
and without nitric oxide synthesis blockade [NG-nitro-l-arginine methyl ester (l
NAME); 5 mg/kg]. We assessed the role of increased cardiac output in mediating
peripheral vasodilation via the slope of the relationship between the rise in
nonischemic vascular conductance (conductance of all vascular beds excluding
hindlimbs) vs. the rise in cardiac output. l-NAME increased mean arterial
pressure at rest and during exercise. The metaboreflex-induced increases in mean
arterial pressure were unaltered by l-NAME, whereas the increases in cardiac
output and nonischemic vascular conductance were attenuated. However, the slope
of the relationship between nonischemic vascular conductance and cardiac output
was not affected by l-NAME, indicating that the rise in cardiac output did not
elicit vasodilation via increased release of nitric oxide. Thus, although nitric
oxide is intrinsic to the vascular tonus, endothelial-dependent flow-mediated
vasodilation plays little role in the small peripheral vasodilation observed
during muscle metaboreflex activation.
PMID- 28490454
TI - Dying together.
PMID- 28490456
TI - Does treadmill running performance, heart rate and breathing rate response during
maximal graded exercise improve after volitional respiratory muscle training?
AB - AIM: Maximal physical exertion in sports usually causes fatigue in the exercising
muscles, but not in the respiratory muscles due to triggering of the Respiratory
muscle metabo-reflex, a sympathetic vasoconstrictor response leading to
preferential increment in blood flow to respiratory muscles.1 We planned to
investigate whether a six week yogic pranayama based Volitional Respiratory
Muscle Training (VRMT) can improve maximal Graded Exercise Treadmill Test (GXTT)
performance in healthy adult recreational sportspersons. METHODS: Consecutive,
consenting healthy adult recreational sportspersons aged 20.56+/-2.49 years
(n=30), volunteered to 'baseline recording' of resting heart rate (HR), blood
pressure (BP), respiratory rate (RR), and Bruce ramp protocol maximal GXTT until
volitional exhaustion providing total test time (TTT), derived VO2max, Metabolic
Equivalent of Task (METs), HR and BP response during maximal GXTT and drop in
recovery HR data. After six weeks of observation, they underwent 'pre
intervention recording' followed by supervised VRMT intervention for 6 weeks (30
minutes a day; 5 days a week) and then 'post-intervention recording'. Repeated
measures ANOVA with pairwise t statistical comparison was used to analyse the
data. RESULTS: After supervised VRMT, we observed significant decrease in their
resting supine RR (p<0.001), resting supine HR (p=0.001), HR after 5 minutes of
assuming standing posture (p=0.003); significant increase in TTT (p<0.001),
derived VO2max (p<0.001), METs (p<0.001) and drop in recovery HR (p=0.038);
altered HR response and BP response during exercise. CONCLUSIONS: We hypothesize
that these changes are probably due to VRMT induced learnt behaviour to control
the breathing pattern that improves breathing economy, improvement in respiratory
muscle aerobic capacity, attenuation of respiratory muscle metabo-reflex,
increase in cardiac stroke volume and autonomic resetting towards parasympatho
dominance. Yogic Pranayama based VRMT can be used in sports conditioning
programme of athletes to further improve their maximal exercise performance, and
as part of rehabilitation training during return from injury.
PMID- 28490455
TI - Speckle tracking echocardiography in acute lupus myocarditis: comparison to
conventional echocardiography.
AB - AIMS: Lupus myocarditis occurs in 5-10% of patients with systemic lupus
erythematosus (SLE). No single feature is diagnostic of lupus myocarditis.
Speckle tracking echocardiography (STE) can detect subclinical left ventricular
dysfunction in SLE patients, with limited research on its utility in clinical
lupus myocarditis. We report on STE in comparison to conventional
echocardiography in patients with clinical lupus myocarditis. METHODS AND
RESULTS: A retrospective study was done at a tertiary referral hospital in South
Africa. SLE patients with lupus myocarditis were included and compared to healthy
controls. Echocardiographic images were reanalyzed, including global longitudinal
strain through STE. A poor echocardiographic outcome was defined as final left
ventricular ejection fraction (LVEF) <40%. 28 SLE patients fulfilled the
criteria. Global longitudinal strain correlated with global (LVEF: r = -0.808; P
= 0.001) and regional (wall motion score: r = 0.715; P < 0.001) function. In
patients presenting with a LVEF >=50%, global longitudinal strain (P = 0.023),
wall motion score (P = 0.005) and diastolic function (P = 0.004) were
significantly impaired vs controls. Following treatment, LVEF (35-47% (P =
0.023)) and wall motion score (1.88-1.5 (P = 0.017)) improved but not global
longitudinal strain. Initial LVEF (34%; P = 0.046) and global longitudinal strain
(-9.5%; P = 0.095) were lower in patients with a final LVEF <40%. CONCLUSIONS:
This is the first known report on STE in a series of patients with clinical lupus
myocarditis. Global longitudinal strain correlated with regional and global left
ventricular function. Global longitudinal strain, wall motion score and diastolic
parameters may be more sensitive markers of lupus myocarditis in patients
presenting with a preserved LVEF >=50%. A poor initial LVEF and global
longitudinal strain were associated with a persistent LVEF <40%. Echocardiography
is a non-invasive tool with diagnostic and prognostic value in lupus myocarditis.
PMID- 28490457
TI - Prognostic factors for musculoskeletal injury identified through medical
screening and training load monitoring in professional football (soccer): a
systematic review.
AB - OBJECTIVES: To identify prognostic factors and models for spinal and lower
extremity injuries in adult professional/elite football players from medical
screening and training load monitoring processes. METHODS: The MEDLINE, AMED,
EMBASE, CINAHL Plus, SPORTDiscus electronic bibliographic databases and the
Cochrane Database of Systematic Reviews were searched from inception to July
2016. Searches were limited to original research, published in peer reviewed
journals of any language. The Quality in Prognostic Studies (QUIPS) tool was used
for appraisal and the modified GRADE approach was used for synthesis. Prospective
and retrospective cohort study designs of spinal and lower extremity injury
incidence were found from populations of adult professional/elite football
players, between 16 and 40 years. Non-football or mixed sports were excluded.
RESULTS: 858 manuscripts were identified. Removing duplications left 551 studies,
which were screened for eligibility by title and abstract. Of these, 531 studies
were not eligible and were excluded. The full text of the remaining 20 studies
were obtained; a further 10 studies were excluded. 10 studies were included for
appraisal and analysis, for 3344 participants. CONCLUSIONS: Due to the paucity
and heterogeneity of the literature, and shortcomings in methodology and
reporting, the evidence is of very low or low quality and therefore cannot be
deemed robust enough to suggest conclusive prognostic factors for all lower limb
musculoskeletal injury outcomes identified. No studies were identified that
examined spinal injury outcomes or prognostic models.
PMID- 28490458
TI - Subcategories of tendinopathy using ultrasound tissue characterization (utc):
dorsal mid-portion achilles tendinopathy is more severe than ventral achilles
tendinopathy.
AB - AIM: To evaluate the association between tendon structure and clinical severity.
Looking specifically at location of pathology, comparing ventral versus dorsal
tendinopathy. METHODS: Patients were recruited from a tertiary tendinopathy
center between Jan 2015 - June 2016. Inclusion criteria included patients with
midportion Achilles tendinopathy, aged between 1870. Patients with insertional
Achilles tendinopathy or other suspected etiology were excluded. Patients were
assessed using ultrasound tissue characterization (UTC) scanning. UTC software
was used to analyse a 2 cm block 24 cm from the calcaneum for percentage of echo
type I, II, III and IV. With percentage echo type I+II used as the primary
outcome. A doctor also categorised patients into predominately dorsal or ventral
pathology based on UTC imaging. VISAA and VAS scores were used for clinical
outcome measures. Statistics were undertaken using SPSS, data was not normally
distributed RESULTS: Overall 33 tendons with mid portion Achilles tendinopathy
were analysed, the overall percentage echo type I+II showed no correlation to
either VISAA (p=0.745, r=0.0600) or VAS (p=0.157, r=0.248). When divided into
dorsal and ventral Achilles tendinopathy there was a significant difference
between baseline VISAA scores with a lower VISAA score 35 (SD+/-19) in dorsal
group compared with the ventral group 60 (SD+/-17.1) (p=0.009). There was also a
higher VAS score in the dorsal group (mean = 6, SD+/-2.28) at baseline compared
with ventral (mean = 5, SD+/-3.07), although this was not significant (p=0.416).
CONCLUSIONS: This highlights the possibility of using UTC to subcategories
patients into ventral and dorsal which seems to correlate to increased clinical
severity in the dorsal group. This is perhaps due to increased tension and
stretching acting through this part of the tendon on loading and thus more
nociceptive stimulation and greater dysfunction of the tendon. This could be used
to help determine differing rehabilitation interventions in future with differing
intensities for the two groups. It further highlights as previous studies1,2 have
that there is no direct correlation between overall structure and clinical
severity.
PMID- 28490459
TI - The heart of the matter: cardiac assessment in professional footballers.
AB - AIM: Sudden cardiac death is the leading medical cause of death during exercise.1
Our objective was to retrospectively analyse the routine cardiac assessment of
professional footballers to aid physician management and improve player safety.
METHODS: Footballers from five professional clubs between March 2012 and October
2014 were included (n=265). All were performed in line with the recommendations
of the Football Association Cardiology Committee, incorporating clinical
examination, 12-lead ECG, echocardiography and health questionnaire.2 Data was
retrospectively collected, inspected and analysed using Excel spreadsheets.
Findings were classified as 'normal' or 'not normal', and not normal assessments
were further broken down into 'clear-cut pathology' (pathology with widely
accepted guidance on management) or 'grey screen'. RESULTS: Footballers were aged
13 to 37 years, with 69% aged over 18 and 31% under. The majority of the review
population was White European (66%). Of the review population 11% had 'not
normal' assessments, of these assessments 83% were considered grey screens (by
Consultant Cardiologist) requiring further investigation or surveillance. Overall
clear-cut pathology was identified in 2%. CONCLUSIONS: A high proportion of the
players (9%) had grey screens. The majority of these were due to ECG or
structural abnormalities, which are clinically challenging to differentiate from
physiological adaptation of the athletic heart and potentially fatal conditions.
The extent to which these findings put the athlete at risk of a life threatening
cardiac event is un-?quantified. Team physician's need to be aware of managing
the on-going risk with these patients and ensure suitable ?follow up and
assessment on a regular basis to mitigate this.
PMID- 28490460
TI - Anxiety, depression and perceived sporting performance among professional cricket
players.
AB - BACKGROUND: Mental health in sport is a hard-hitting topic that is frequently the
subject of news coverage and increasingly a theme for avid research. Some suggest
that cricketers, participating in a game unique in its statistical analysis of
individual performance, prolonged periods of play away from home and extended
solitary game time to reflect on errors, may be especially prone to developing
depression. This hypothesis is supported by a higher rate of suicide among male
Test cricketers when compared with the UK male general population.1 METHODS: This
study ascertained rates of anxiety and depression by screening professional
cricket players using the Generalised Anxiety Disorder Questionnaire (GAD-7) and
Patient Health Questionnaire (PHQ-9). It also investigate whether professional
cricket players perceive stress and anxiety to be beneficial to their sporting
performance. 21 male professional cricketers were included in this anonymous
questionnaire based study. RESULTS: Six players had a positive depression screen,
five scoring mild and one scoring moderate. Additionally, six players had a
positive anxiety screen, four scoring mild and two ?players within the moderate
range. Fifteen players thought pre-match stress and anxiety was beneficial to
their sporting performance. Of these, nine thought slight, five thought fair and
one thought considerable levels were optimal. CONCLUSIONS: Undiagnosed anxiety
and depression may exist in professional cricket teams and as such better
screening is required. The majority of players feel some level of stress and
tension are beneficial for their performance, with a slight amount being the most
common perceived optimum.
PMID- 28490461
TI - Quality of life among children with spina bifida in Uganda.
AB - BACKGROUND: Children surviving after spina bifida repair often have significant
disability, the consequences of which may be more profound in low-income
countries. The aim of this cross-sectional study was to measure quality of life
(QOL) reported by children with spina bifida in Uganda, and to define factors
associated with QOL. METHODS: QOL was measured using both the Health Utilities
Index (HUI3) Tool and a visual analogue scale (VAS) marked from 0 to 10. In
keeping with the WHO definition of QOL, further analysis was conducted using
subjective QOL scores (using the VAS). Multivariate regression was used to
investigate the association between VAS scores and prespecified variables: age,
sex, hydrocephalus, mobility, urinary continence, school attendance and family
size. RESULTS: Sixty two of 68 surviving children aged 10-14 were able to
complete all aspects of the assessment. There was poor correlation between the
VAS and HUI3 Tool (Pearson correlation 0.488). On multivariate regression, the
following variables were associated with a significant change in the 10-point VAS
(change in score; 95% CI): male sex (-1.45; -2.436 to -0.465), urinary continence
(1.681; 0.190 to 3.172), large family size (-1.775; -2.773 to -0.777) and
hydrocephalus (-1.382; -2.374 to -0.465). CONCLUSIONS: Urinary continence and
family size are potentially modifiable, the former by simple and inexpensive
medical management. Enhanced investment in community-based rehabilitation and
support is urgently needed. Delivery of family planning services is a national
priority in Uganda, and should be discussed with families as part of holistic
care.
PMID- 28490462
TI - Genome-wide DNA Methylation Analysis Reveals GABBR2 as a Novel Epigenetic Target
for EGFR 19 Deletion Lung Adenocarcinoma with Induction Erlotinib Treatment.
AB - Purpose: The past decade has witnessed the rapid development of personalized
targeted therapies in lung cancer. It is still unclear whether epigenetic changes
are involved in the response to tyrosine kinase inhibitor (TKI) treatment in
epidermal growth factor receptor (EGFR)-mutated lung cancer.Experimental Design:
Methyl-sensitive cut counting sequencing (MSCC) was applied to investigate the
methylation changes in paired tissues before and after erlotinib treatment for 42
days with partial response (PR) from stage IIIa (N2) lung adenocarcinoma patients
(N = 2) with EGFR 19 deletion. The Sequenom EpiTYPER assay was used to validate
the changed methylated candidate genes. Up- or downregulation of the candidate
gene was performed to elucidate the potential mechanism in the regulation of
erlotinib treatment response.Results: Sixty aberrant methylated genes were
screened using MSCC sequencing. Two aberrant methylated genes, CBFA2T3 and
GABBR2, were clearly validated. A same differential methylated region (DMR)
between exon 2 and exon 3 of GABBR2 gene was confirmed consistently in both
patients. GABBR2 was significantly downregulated in EGFR 19 deletion cells,
HCC4006 and HCC827, but remained conserved in EGFR wild-type A549 cells after
erlotinib treatment. Upregulation of GABBR2 expression significantly rescued
erlotinib-induced apoptosis in HCC827 cells. GABBR2 was significantly
downregulated, along with the reduction of S6, p-p70 S6, and p-ERK1/2,
demonstrating that GABBR2 may play an important role in EGFR signaling through
the ERK1/2 pathway.Conclusions: We demonstrated that GABBR2 gene might be a novel
potential epigenetic treatment target with induction erlotinib treatment for
stage IIIa (N2) EGFR 19 deletion lung adenocarcinoma. Clin Cancer Res; 23(17);
5003-14. (c)2017 AACR.
PMID- 28490463
TI - A First-in-Human, Phase I, Dose-Escalation Study of TAK-117, a Selective
PI3Kalpha Isoform Inhibitor, in Patients with Advanced Solid Malignancies.
AB - Purpose: To evaluate the safety, MTD, pharmacokinetics, pharmacodynamics, and
preliminary antitumor activity of TAK-117 (MLN1117/INK1117), an investigational
PI3Kalpha-selective inhibitor, in patients with advanced solid
tumors.Experimental Design: Seventy-one patients received oral TAK-117 once daily
[100-300 mg (n = 24)] or 3 days per week [Monday-Wednesday-Friday (MWF), 200
1,200 mg (n = 27); Monday-Tuesday-Wednesday (MTuW), 200-900 mg (n = 20)], in 21
day cycles. Dose escalation proceeded via a 3 + 3 design.Results: TAK-117 once
daily dosing was associated with dose-limiting grade >=3 alanine/aspartate
aminotransferase (ALT/AST) elevations, resulting in a narrow range of tolerable
doses (100-150 mg once daily). With MWF/MTuW dosing, no dose-limiting ALT/AST
elevations occurred until the MTD of 900 mg; total weekly dose was 2.6-fold that
of 150 mg once daily. Drug-related grade >=3 adverse events occurred in
25%/22%/35% (including hyperglycemia in 0%/7%/15%) of once-daily/MWF/MTuW
patients. TAK-117 (100-1,200 mg) exhibited moderately fast oral absorption, a
generally dose proportional increase in exposure, and plasma half-life of
approximately 11 hours. Total weekly exposures with 900 mg MWF/MTuW dosing were
approximately 4 times greater than with 150 mg once daily. Skin pS6 expression
was suppressed at >=200 mg. There were 3/1/0 partial responses (once
daily/MWF/MTuW) and 5/7/5 patients had stable disease lasting >=3 months (all
PIK3CA mutated).Conclusions: Intermittent dosing of TAK-117 had an acceptable
safety profile and enabled higher doses and total weekly exposures versus once
daily dosing. Although the potential for TAK-117 as single-agent therapy appears
limited, further evaluation in combination approaches for advanced solid tumors
is warranted. Clin Cancer Res; 23(17); 5015-23. (c)2017 AACR.
PMID- 28490464
TI - Perioperative COX-2 and beta-Adrenergic Blockade Improves Metastatic Biomarkers
in Breast Cancer Patients in a Phase-II Randomized Trial.
AB - Purpose: Translational studies suggest that excess perioperative release of
catecholamines and prostaglandins may facilitate metastasis and reduce disease
free survival. This trial tested the combined perioperative blockade of these
pathways in breast cancer patients.Experimental Design: In a randomized placebo
controlled biomarker trial, 38 early-stage breast cancer patients received 11
days of perioperative treatment with a beta-adrenergic antagonist (propranolol)
and a COX-2 inhibitor (etodolac), beginning 5 days before surgery. Excised tumors
and sequential blood samples were assessed for prometastatic biomarkers.Results:
Drugs were well tolerated with adverse event rates comparable with placebo.
Transcriptome profiling of the primary tumor tested a priori hypotheses and
indicated that drug treatment significantly (i) decreased epithelial-to
mesenchymal transition, (ii) reduced activity of prometastatic/proinflammatory
transcription factors (GATA-1, GATA-2, early-growth-response-3/EGR3, signal
transducer and activator of transcription-3/STAT-3), and (iii) decreased tumor
infiltrating monocytes while increasing tumor-infiltrating B cells. Drug
treatment also significantly abrogated presurgical increases in serum IL6 and C
reactive protein levels, abrogated perioperative declines in stimulated IL12 and
IFNgamma production, abrogated postoperative mobilization of CD16- "classical"
monocytes, and enhanced expression of CD11a on circulating natural killer
cells.Conclusions: Perioperative inhibition of COX-2 and beta-adrenergic
signaling provides a safe and effective strategy for inhibiting multiple cellular
and molecular pathways related to metastasis and disease recurrence in early
stage breast cancer. Clin Cancer Res; 23(16); 4651-61. (c)2017 AACR.
PMID- 28490465
TI - Dual Inhibition of EZH2 and EZH1 Sensitizes PRC2-Dependent Tumors to Proteasome
Inhibition.
AB - Purpose: EZH2 and EZH1, the catalytic components of polycomb repressive complex 2
(PRC2), trigger trimethylation of H3K27 (H3K27me3) to repress the transcription
of target genes and are implicated in the pathogenesis of various cancers
including multiple myeloma and prostate cancer. Here, we investigated the
preclinical effects of UNC1999, a dual inhibitor of EZH2 and EZH1, in combination
with proteasome inhibitors on multiple myeloma and prostate cancer.Experimental
Design:In vitro and in vivo efficacy of UNC1999 and the combination with
proteasome inhibitors was evaluated in multiple myeloma cell lines, primary
patient cells, and in a xenograft model. RNA-seq and ChIP-seq were performed to
uncover the targets of UNC1999 in multiple myeloma. The efficacy of the
combination therapy was validated in prostate cancer cell lines.Results:
Proteasome inhibitors repressed EZH2 transcription via abrogation of the RB-E2F
pathway, thereby sensitizing EZH2-dependent multiple myeloma cells to EZH1
inhibition by UNC1999. Correspondingly, combination of proteasome inhibitors with
UNC1999, but not with an EZH2-specific inhibitor, induced synergistic antimyeloma
activity in vitro Bortezomib combined with UNC1999 remarkably inhibited the
growth of myeloma cells in vivo Comprehensive analyses revealed several direct
targets of UNC1999 including the tumor suppressor gene NR4A1 Derepression of
NR4A1 by UNC1999 resulted in suppression of MYC, which was enhanced by the
combination with bortezomib, suggesting the cooperative blockade of PRC2
function. Notably, this combination also exhibited strong synergy in prostate
cancer cells.Conclusions: Our results identify dual inhibition of EZH2 and EZH1
together with proteasome inhibition as a promising epigenetics-based therapy for
PRC2-dependent cancers. Clin Cancer Res; 23(16); 4817-30. (c)2017 AACR.
PMID- 28490466
TI - RET Signaling in Prostate Cancer.
AB - Purpose: Large diameter perineural prostate cancer is associated with poor
outcomes. GDNF, with its coreceptor GFRalpha1, binds RET and activates downstream
pro-oncogenic signaling. Because both GDNF and GFRalpha1 are secreted by nerves,
we examined the role of RET signaling in prostate cancer.Experimental Design:
Expression of RET, GDNF, and/or GFRalpha1 was assessed. The impact of RET
signaling on proliferation, invasion and soft agar colony formation, perineural
invasion, and growth in vivo was determined. Cellular signaling downstream of RET
was examined by Western blotting.Results: RET is expressed in all prostate cancer
cell lines. GFRalpha1 is only expressed in 22Rv1 cells, which is the only line
that responds to exogenous GDNF. In contrast, all cell lines respond to GDNF plus
GFRalpha1. Conditioned medium from dorsal root ganglia contains secreted
GFRalpha1 and promotes transformation-related phenotypes, which can be blocked by
anti-GFRalpha1 antibody. Perineural invasion in the dorsal root ganglion assay is
inhibited by anti-GFRalpha antibody and RET knockdown. In vivo, knockdown of RET
inhibits tumor growth. RET signaling activates ERK or AKT signaling depending on
context, but phosphorylation of p70S6 kinase is markedly increased in all cases.
Knockdown of p70S6 kinase markedly decreases RET induced transformed phenotypes.
Finally, RET is expressed in 18% of adenocarcinomas and all three small-cell
carcinomas examined.Conclusions: RET promotes transformation associated
phenotypes, including perineural invasion in prostate cancer via activation of
p70S6 kinase. GFRalpha1, which is secreted by nerves, is a limiting factor for
RET signaling, creating a perineural niche where RET signaling can occur. Clin
Cancer Res; 23(16); 4885-96. (c)2017 AACR.
PMID- 28490467
TI - Dose Optimization to Minimize Radiation Risk for Children Undergoing CT and
Nuclear Medicine Imaging Is Misguided and Detrimental.
AB - A debate exists within the medical community on whether the linear no-threshold
model of ionizing radiation exposure accurately predicts the subsequent incidence
of radiogenic cancer. In this article, we evaluate evidence refuting the linear
no-threshold model and corollary efforts to reduce radiation exposure from CT and
nuclear medicine imaging in accord with the as-low-as-reasonably-achievable
principle, particularly for children. Further, we review studies demonstrating
that children are not, in fact, more radiosensitive than adults in the radiologic
imaging dose range, rendering dose reduction for children unjustifiable and
counterproductive. Efforts to minimize nonexistent risks are futile and a major
source of persistent radiophobia. Radiophobia is detrimental to patients and
parents, induces stress, and leads to suboptimal image quality and avoidance of
imaging, thus increasing misdiagnoses and consequent harm while offering no
compensating benefits.
PMID- 28490468
TI - Is Tau Imaging More Than Just Upside-Down 18F-FDG Imaging?
PMID- 28490469
TI - Management Impact of Imaging Brain Vesicular Monoamine Transporter Type 2 in
Clinically Uncertain Parkinsonian Syndrome with 18F-AV133 and PET.
AB - Idiopathic Parkinson disease is a common neurodegenerative disorder for which
misdiagnosis occurs in up to 30% of patients after initial assessment and in 10%
15% even after long-term follow-up. Vesicular monoamine transporter type 2
(VMAT2) imaging with PET allows assessment of the integrity of the presynaptic
dopaminergic pathway. We investigated the management impact of VMAT2 imaging in
patients with clinically uncertain Parkinsonian syndromes. Methods: Forty-seven
patients with clinically uncertain Parkinsonian syndromes (mean age +/- SD, 56.9
+/- 14.9 y; age range, 21-80 y) were referred from movement disorder specialists.
All participants underwent a 20-min PET acquisition 2 h after injection of 250
MBq of 18F-AV-133, and the resulting images were quantitatively assessed.
Clinical impact was recorded as high, moderate, or low based on diagnosis and
management questionnaires completed by the referring specialists before and after
release of the PET results. Management impact was high if there was a change in
diagnostic category, moderate if there was a change in medication, and low if
there was no change. Results: VMAT2 PET changed the diagnosis in 11 (23%) and
medication in 25 (53%) participants. Management impact was high in 23%, moderate
in 38%, and low in 39% of the participants. High diagnostic confidence increased
from 11% of patients to 80% after the release of the scan results. Conclusion:18F
AV-133 had substantial management impact in patients with clinically uncertain
Parkinsonian syndromes. VMAT2 imaging with 18F-AV133 might improve diagnosis,
prognosis, and appropriate use of medication, translating into better patient
outcomes.
PMID- 28490470
TI - Metal Artifact Reduction of CT Scans to Improve PET/CT.
AB - In recent years, different metal artifact reduction methods have been developed
for CT. These methods have only recently been introduced for PET/CT even though
they could be beneficial for interpretation, segmentation, and quantification of
the PET/CT images. In this study, phantom and patient scans were analyzed
visually and quantitatively to measure the effect on PET images of iterative
metal artifact reduction (iMAR) of CT data. Methods: The phantom consisted of 2
types of hip prostheses in a solution of 18F-FDG and water. 18F-FDG PET/CT scans
of 14 patients with metal implants (either dental implants, hip prostheses,
shoulder prostheses, or pedicle screws) and 68Ga-labeled prostate-specific
membrane antigen (68Ga-PSMA) PET/CT scans of 7 patients with hip prostheses were
scored by 2 experienced nuclear medicine physicians to analyze clinical
relevance. For all patients, a lesion was located in the field of view of the
metal implant. Phantom and patients were scanned in a PET/CT scanner. The
standard low-dose CT scans were processed with the iMAR algorithm. The PET data
were reconstructed using attenuation correction provided by both standard CT and
iMAR-processed CT. Results: For the phantom scans, cold artifacts were visible on
the PET image. There was a 30% deficit in 18F-FDG concentration, which was
restored by iMAR processing, indicating that metal artifacts on CT images induce
quantification errors in PET data. The iMAR algorithm was useful for most
patients. When iMAR was used, the confidence in interpretation increased or
stayed the same, with an average improvement of 28% +/- 20% (scored on a scale of
0%-100% confidence). The SUV increase or decrease depended on the type of metal
artifact. The mean difference in absolute values of SUVmean of the lesions was
3.5% +/- 3.3%. Conclusion: The iMAR algorithm increases the confidence of the
interpretation of the PET/CT scan and influences the SUV. The added value of iMAR
depends on the indication for the PET/CT scan, location and size/type of the
prosthesis, and location and extent of the disease.
PMID- 28490471
TI - Analysis of Prognostic Values of Various PET Metrics in Preoperative 18F-FDG PET
for Early-Stage Bronchial Carcinoma for Progression-Free and Overall Survival:
Significantly Increased Glycolysis Is a Predictive Factor.
AB - The purpose of this study was to assess various volume-based PET quantification
metrics, including metabolic tumor volume and total lesion glycolysis (TLG) with
different thresholds, as well as background activity-based PET metrics
(background-subtracted lesion activity [BSL] and background-subtracted volume) as
prognostic markers for progression-free and overall survival (PFS and OS,
respectively) in early-stage I and II non-small cell lung cancer (NSCLC) after
resection. Methods: Patients (n = 133) underwent an adequate 18F-FDG PET/CT scan
before surgery between January 2003 and December 2010. All PET activity metrics
showed a skewed distribution and were log-transformed before calculation of the
Pearson correlation coefficients. Survival tree analysis was used to discriminate
between high- and low-risk patients and to select the most important prognostic
markers. The Akaike information criterion was used to compare 2 univariate
models. Results: Within the study time, 36 patients died from NSCLC and 26
patients from other causes. At the end of follow-up, 70 patients were alive, with
67 patients being free of disease. All log-transformed PET metrics showed a
strong linear association, with a Pearson correlation coefficient between 0.703
and 0.962. After multiple testing corrections, only 1 prognostic marker
contributed a significant split point in the survival tree analysis. Of 10
potential predictors including 7 PET metrics, a BSL greater than 6,852 (P =
0.017) was chosen as split point, assigning 13 patients into a high-risk group.
If BSL was removed from the set of predictors, a 42% TLG (TLG42%) of greater than
4,204 (P = 0.023) was chosen as split point. When a dichotomized BSL or TLG42%
variable was used for a univariate Cox model, the Akaike information criterion
difference of both models was smaller than 2; therefore, the data do not provide
evidence that 1 of the 2 prognostic factors is superior. Conclusion: Volume-based
PET metrics correlate with PFS and OS and could be used for risk assessment in
stage I-II NSCLC. The different PET metrics assessed in this study showed a high
correlation; therefore, it is not surprising that there was no significant
difference to predict PFS or OS within this study. Overall, patients with large
and metabolically active tumors should be considered high risk and might need
further treatment after resection. Because all analysis steps were done with the
same data, these results should be validated on new patient data.
PMID- 28490472
TI - 18F-FDG PET/CT for Very Early Response Evaluation Predicts CT Response in
Erlotinib-Treated Non-Small Cell Lung Cancer Patients: A Comparison of Assessment
Methods.
AB - The purpose of this study was to determine which method for early response
evaluation with 18F-FDG PET/CT performed most optimally for the prediction of
response on a later CT scan in erlotinib-treated non-small cell lung cancer
patients. Methods:18F-FDG PET/CT scans were obtained before and after 7-10 d of
erlotinib treatment in 50 non-small cell lung cancer patients. The scans were
evaluated using a qualitative approach and various semiquantitative methods
including percentage change in SUVs, lean body mass-corrected (SUL) SULpeak,
SULmax, and total lesion glycolysis (TLG). The PET parameters and their
corresponding response categories were compared with the percentage change in the
sum of the longest diameter in target lesions and the resulting response
categories from a CT scan obtained after 9-11 wk of erlotinib treatment using
receiver-operating-characteristic analysis, linear regression, and quadratic
weighted kappa. Results: TLG delineation according to the PERCIST showed the
strongest correlation to sum of the longest diameter (R = 0.564, P < 0.001),
compared with SULmax (R = 0.298, P = 0.039) and SULpeak (R = 0.402, P = 0.005).
For predicting progression on CT, receiver-operating-characteristic analysis
showed area under the curves between 0.79 and 0.92, with the highest area under
the curve of 0.92 (95% confidence interval [CI], 0.84-1.00) found for TLG
(PERCIST). Furthermore, the use of a cutoff of 25% change in TLG (PERCIST) for
both partial metabolic response and progressive metabolic disease, which is the
best predictor of the CT response categories, showed a kappa-value of 0.53 (95%
CI, 0.31-0.75). This method identifies 41% of the later progressive diseases on
CT, with no false-positives. Visual evaluation correctly categorized 50%, with a
kappa-value of 0.47 (95% CI, 0.24-0.70). Conclusion: TLG (PERCIST) was the
optimal predictor of response on later CT scans, outperforming both SULpeak and
SULmax The use of TLG (PERCIST) with a 25% cutoff after 1-2 wk of treatment
allows us to safely identify 41% of the patients who will not benefit from
erlotinib and stop the treatment at this time.
PMID- 28490473
TI - Specific Imaging of Bacterial Infection Using 6"-18F-Fluoromaltotriose: A Second
Generation PET Tracer Targeting the Maltodextrin Transporter in Bacteria.
AB - 6"-18F-fluoromaltotriose is a PET tracer that can potentially be used to image
and localize most bacterial infections, much like 18F-FDG has been used to image
and localize most cancers. However, unlike 18F-FDG, 6"-18F-fluoromaltotriose is
not taken up by inflammatory lesions and appears to be specific to bacterial
infections by targeting the maltodextrin transporter that is expressed in gram
positive and gram-negative strains of bacteria. Methods: 6"-18F-fluoromaltotriose
was synthesized with high radiochemical purity and evaluated in several
clinically relevant bacterial strains in cultures and in living mice. Results: 6"
18F-fluoromaltotriose was taken up in both gram-positive and gram-negative
bacterial strains. 6"-18F-fluoromaltotriose was also able to detect Pseudomonas
aeruginosa in a clinically relevant mouse model of wound infection. The utility
of 6"-18F-fluoromaltotriose to help monitor antibiotic therapies was also
evaluated in rats. Conclusion: 6"-18F-fluoromaltotriose is a promising new tracer
that has significant diagnostic utility, with the potential to change the
clinical management of patients with infectious diseases of bacterial origin.
PMID- 28490474
TI - The mechanics of microtubule networks in cell division.
AB - The primary goal of a dividing somatic cell is to accurately and equally
segregate its genome into two new daughter cells. In eukaryotes, this process is
performed by a self-organized structure called the mitotic spindle. It has long
been appreciated that mechanical forces must be applied to chromosomes. At the
same time, the network of microtubules in the spindle must be able to apply and
sustain large forces to maintain spindle integrity. Here we consider recent
efforts to measure forces generated within microtubule networks by ensembles of
key proteins. New findings, such as length-dependent force generation, protein
clustering by asymmetric friction, and entropic expansion forces will help
advance models of force generation needed for spindle function and maintaining
integrity.
PMID- 28490475
TI - Conservatives and Labour trade blows on NHS.
PMID- 28490477
TI - Bilateral corneal injury after face-paint application to upper eyelids.
AB - A 40-year-old woman with no known medical conditions or allergies presented with
severely painful, watery eyes and blurred vision. She reported topical
application of face-paint onto both upper eyelids prior to attending a Halloween
party. She subsequently noticed a burning sensation, epiphora and misty vision
within a few hours. On examination, bilateral large corneal epithelial defects
were highlighted with fluorescein dye under cobalt-blue light. Antibiotic
ointment, mydriatic and sodium ascorbate 10% eye-drops were given, and patient
was advised to keep the eyelids shut to promote healing. No corneal defects were
visible by day 4 and the patient was discharged with vision recovering to normal
levels.
PMID- 28490476
TI - Socioeconomic status in childhood and C reactive protein in adulthood: a
systematic review and meta-analysis.
AB - BACKGROUND: Inflammation plays a central role in cardiometabolic disease and may
represent a mechanism linking low socioeconomic status (SES) in early life and
adverse cardiometabolic health outcomes in later life. Accumulating evidence
suggests an association between childhood SES and adult inflammation, but
findings have been inconsistent. METHODS: We conducted a systematic review and
meta-analysis of observational studies to quantify the association between
childhood (age <18 years) SES and the inflammatory marker C reactive protein
(CRP) in adulthood. Studies were identified in Medline and Embase databases, and
by reviewing the bibliographies of articles published from 1946 to December 2015.
Study-specific estimates were combined into meta-analyses using random-effects
models. RESULTS: 15 of 21 eligible studies (n=43 629) were ultimately included in
two separate meta-analyses. Compared with those from the most advantaged
families, participants from the least advantaged families had 25% higher CRP
levels (ratio change in geometric mean CRP: 1.25; 95% CI 1.19 to 1.32) in
minimally adjusted analyses. This finding was attenuated by the inclusion of
adult body mass index (BMI) in adjusted models, suggesting BMI has a strong
mediating role in CRP levels. CONCLUSIONS: We observed an inverse association
between childhood SES and adulthood CRP, potentially mediated through BMI.
Investigating how childhood SES is associated with childhood BMI and CRP would
provide insight into the effective timing of social and clinical interventions to
prevent cardiometabolic disease.
PMID- 28490478
TI - Mixed cryoglobulinemia: a diagnostic and therapeutic challenge.
AB - Mixed cryoglobulinemia is frequently secondary to hepatitis C virus infection.
Diagnosis and therapeutic management are challenging, depending on the spectrum
and severity of manifestations, as well as on the presence of comorbidities. We
describe a case of a 79-year-old woman with a non-cirrhotic hepatitis C virus
infection presenting with weakness, arthralgias, purpuric rash with left leg
ulcerative lesions, bilateral peripheral sensorimotor polyneuropathy, renal
impairment and cardiac failure. The investigation was compatible with a severe
type II mixed cryoglobulinemia with multisystemic involvement, including a low
grade B cell lymphoma and concomitant intestinal tuberculosis. Initial management
with immunosuppressive therapy with glucocorticoids to control symptoms and
simultaneous tuberculosis treatment was required. Unavailability of adequate
antiviral treatment led to the need to control the severity of systemic
manifestations with rituximab, before the effective aetiological treatment with
sofosbuvir and ledipasvir was possible, allowing the definitive resolution of the
disease.
PMID- 28490479
TI - Cystic adventitial disease of the common femoral vein.
AB - We present the case of a 46-year-old commercial pilot with a history of
unilateral leg swelling following a flight to Geneva. Although initial clinical
examination suggested a deep vein thrombosis, the swelling only partially
resolved with anticoagulation and further imaging suggested the presence of
adventitial cystic disease (ACD). The patient underwent initial anticoagulation
to allow any thrombus to be lysed, followed by excision of the ACD from the
venous wall and venous reconstruction. Following the excision of the ACD,
providing the patient remains asymptomatic and further imaging finds normal
venous anatomy, we hope the patient will discontinue anticoagulation and return
to flying.
PMID- 28490480
TI - A rare view: giant liver abscess with underlying liver metastases.
PMID- 28490481
TI - Vitamin A deficiency due to chronic malabsorption: an ophthalmic manifestation of
a systemic condition.
AB - A 47-year-old woman presented with a 4-week history of progressive loss of
vision, first manifesting as night blindness. Additionally, the patient reported
frequent severe episodes of diarrhoea over the past month. Her medical history
included end-stage renal failure for which she was currently on haemodialysis
after a failed renal transplant, chronic pancreatitis and autonomic diabetes
mellitus. Ophthalmological examination revealed severe bilateral corneal xerosis,
bilateral Bitot's spots and inferior ulceration of the right cornea. A diagnosis
of xerophthalmia due to vitamin A deficiency was made, most likely due to the
presence of small intestinal bacterial overgrowth and the patient's chronic
malabsorptive state. Standard management using oral vitamin A tablets was
ineffective, resulting in the patient requiring intravenous supplementation. The
extent of visual deterioration on presentation and the difficulties encountered
managing the patient resulted in the patient's vision failing to improve.
PMID- 28490482
TI - Conditional ablation of Raptor in the male germline causes infertility due to
meiotic arrest and impaired inactivation of sex chromosomes.
AB - Rapamycin is a clinically important drug that is used in transplantation and
cancer therapy but which causes a number of side effects, including male
infertility. Its canonical target, mammalian target of rapamycin complex 1
(mTORC1), plays a key role in metabolism and binds chromatin; however, its
precise role in the male germline has not been elucidated. Here, we inactivate
the core component, Raptor, to show that mTORC1 function is critical for male
meiosis and the inactivation of sex chromosomes. Disruption of the Raptor gene
impairs chromosomal synapsis and prevents the efficient spreading of silencing
factors into the XY chromatin. Accordingly, mRNA for XY-linked genes remains
inappropriately expressed in Raptor-deficient mice. Molecularly, the failure to
suppress gene expression corresponded with deficiencies in 2 repressive chromatin
markers, H3K9 dimethylation and H3K9 trimethylation, in the XY body. Together,
these results demonstrate that mTORC1 has an essential role in the meiotic
progression and silencing of sex chromosomes in the male germline, which may
explain the infertility that has been associated with such inhibitors as
rapamycin.-Xiong, M., Zhu, Z., Tian, S., Zhu, R., Bai, S., Fu, K., Davis, J. G.,
Sun, Z., Baur, J. A., Zheng, K., Ye, L. Conditional ablation of Raptor in the
male germline causes infertility due to meiotic arrest and impaired inactivation
of sex chromosomes.
PMID- 28490484
TI - Developing a decision rule to optimise clinical pharmacist resources for
medication reconciliation in the emergency department.
AB - BACKGROUND: The process of obtaining a complete medication history for patients
admitted to the hospital from the ED at hospital admission, without
discrepancies, is error prone and time consuming. OBJECTIVES: The goal of this
study was the development of a clinical decision rule (CDR) with a high positive
predictive value in detecting ED patients admitted to hospital at risk of at
least one discrepancy during regular medication history acquisition, along with
favourable feasibility considering time and budget constraints. METHODS: Data
were based on a previous prospective study conducted at the ED in Belgium,
describing discrepancies in 3592 medication histories. Data were split into a
training and a validation set. A model predicting the number of discrepancies was
derived from the training set with negative binomial regression and was validated
on the validation set. The performance of the model was assessed. Several CDRs
were constructed and evaluated on positive predictive value and alert rate.
RESULTS: The following variables were retained in the prediction model: (1) age,
(2) gender, (3) medical discipline for which the patient was admitted, (4) degree
of physician training, (5) season of admission, (6) type of care before
admission, number of (7) drugs, (8) high-risk drugs, (9) drugs acting on
alimentary tract and metabolism, (10) antithrombotics, antihaemorrhagics and
antianaemic preparations, (11) cardiovascular drugs, (12) drugs acting on
musculoskeletal system and (13) drugs acting on the nervous system; all recorded
by the ED physician on admission. The final CDR resulted in an alert rate of 29%
with a positive predictive value of 74%. CONCLUSION: The final CDR allows
identification of the majority of patients with a potential discrepancy within a
feasible workload for the pharmacy staff. Our CDR is a first step towards a rule
that could be incorporated into electronic medical records or a scoring system.
PMID- 28490483
TI - The ratio of dihomo-gamma-linolenic acid to deoxycholic acid species is a
potential biomarker for the metabolic abnormalities in obesity.
AB - Bile acid (BA) signaling regulates fatty acid metabolism. BA dysregulation plays
an important role in the development of metabolic disease. However, BAs in
relation to fatty acids have not been fully investigated in obesity-related
metabolic disorders. A targeted metabolomic measurement of serum BA and free
fatty acid profiles was applied to sera of 381 individuals in 2 independent
studies. The results showed that the ratio of dihomo-gamma-linolenic acid (DGLA)
to deoxycholic acid (DCA) species (DCAS) was significantly increased in obese
individuals with type 2 diabetes (T2DM) from a case-control study and decreased
in the remission group of obese subjects with T2DM after metabolic surgery. The
changes were closely associated with their metabolic status. These results were
consistently confirmed in both serum and liver of mice with diet-induced obesity,
implying that such a metabolic alteration in circulation reflects changes
occurring in the liver. In vitro studies of human liver L-02 cell lines under BA
treatment revealed that DCA and its conjugated form, TDCA, significantly
inhibited mRNA expression of fatty acid transport protein 5 in the presence of
DGLA, which was involved in hepatocyte DGLA uptake. Thus, the DGLA:DCAS ratio may
be a promising biomarker for metabolic abnormalities in obesity.-Lei, S., Huang,
F., Zhao, A., Chen, T., Chen, W., Xie, G., Zheng, X., Zhang, Y., Yu, H., Zhang,
P., Rajani, C., Bao, Y., Jia, W., Jia, W. The ratio of dihomo-gamma-linolenic
acid to deoxycholic acid species is a potential biomarker for the metabolic
abnormalities in obesity.
PMID- 28490485
TI - Molecular Characterization of Mycoplasma pneumoniae Infections in Two Rural
Populations of Thailand from 2009 to 2012.
AB - Studies on Mycoplasma pneumoniae in Thailand have focused on urban centers and
have not included molecular characterization. In an attempt to provide a more
comprehensive understanding of this organism, we conducted a systematic random
sampling to identify 3,000 nasopharyngeal swab specimens collected from January
2009 through July 2012 during population-based surveillance for influenza-like
illness in two rural provinces. M. pneumoniae was detected by real-time PCR in
175 (5.8%) specimens. Genotyping was performed using the major adhesion protein
(P1) and multilocus variable-number tandem-repeat analysis (MLVA). Of the 157
specimens typed, 97 were P1 type 1 and 60 were P1 type 2. Six different MLVA
profiles were identified in 149 specimens, with 4/5/7/2 (40%) and 3/5/6/2 (26%)
predominating. There was no discrete seasonality to M. pneumoniae infections.
Examination of the 23S rRNA sequence for known polymorphisms conferring macrolide
resistance revealed that all 141 tested to possess the genotype associated with
macrolide susceptibility.
PMID- 28490486
TI - Meatal Swabs Contain Less Cellular Material and Are Associated with a Decrease in
Gram Stain Smear Quality Compared to Urethral Swabs in Men.
AB - Urethral swabs are the samples of choice for point-of-care Gram stain testing to
diagnose Neisseria gonorrhoeae infection and nongonococcal urethritis (NGU) in
men. As an alternative to urethral swabs, meatal swabs have been recommended for
the collection of urethral discharge to diagnose N. gonorrhoeae and Chlamydia
trachomatis infection in certain populations by nucleic acid amplification
testing (NAAT), as they involve a less invasive collection method. However, as
meatal swabs could be sampling a reduced surface area and result in fewer
collected epithelial cells compared to urethral swabs, the adequacy of meatal
swab specimens to collect sufficient cellular material for Gram stain testing
remains unknown. We enrolled 66 men who underwent either urethral or meatal
swabbing and compared the cellular content and Gram stain failure rate. We
measured the difference in swab cellular content using the Cepheid Xpert CT/NG
sample adequacy control crossing threshold (SACCT) and determined the failure
rate of Gram stain smears (GSS) due to insufficient cellular material. In the
absence of discharge, meatal smears were associated with a significant reduction
in cellular content (P = 0.0118), which corresponded with a GSS failure rate
significantly higher than that for urethral swabs (45% versus 3%, respectively; P
< 0.0001). When discharge was present, there was no difference among results from
urethral and meatal swabs. Therefore, if GSS testing is being considered for
point-of-care diagnosis of N. gonorrhoeae infection or NGU in men, meatal swabs
should be avoided in the absence of a visible discharge.
PMID- 28490487
TI - Bifidobacterium Bacteremia: Clinical Characteristics and a Genomic Approach To
Assess Pathogenicity.
AB - Bifidobacteria are commensals that colonize the orogastrointestinal tract and
rarely cause invasive human infections. However, an increasing number of
bifidobacterial blood culture isolates has lately been observed in Norway. In
order to investigate the pathogenicity of the Bifidobacterium species responsible
for bacteremia, we studied Bifidobacterium isolates from 15 patients for whom
cultures of blood obtained from 2013 to 2015 were positive. We collected clinical
data and analyzed phenotypic and genotypic antibiotic susceptibility. All
isolates (11 Bifidobacterium longum, 2 B. breve, and 2 B. animalis isolates) were
subjected to whole-genome sequencing. The 15 patients were predominantly in the
extreme lower or upper age spectrum, many were severely immunocompromised, and 11
of 15 had gastrointestinal tract-related conditions. In two elderly patients, the
Bifidobacterium bacteremia caused a sepsis-like picture, interpreted as the cause
of death. Most bifidobacterial isolates had low MICs (<=0.5 mg/liter) to beta
lactam antibiotics, vancomycin, and clindamycin and relatively high MICs to
ciprofloxacin and metronidazole. We performed a pangenomic comparison of invasive
and noninvasive B. longum isolates based on 65 sequences available from GenBank
and the sequences of 11 blood culture isolates from this study. Functional
annotation identified unique genes among both invasive and noninvasive isolates
of Bifidobacterium Phylogenetic clusters of invasive isolates were identified for
a subset of the B. longum subsp. longum isolates. However, there was no
difference in the number of putative virulence genes between invasive and
noninvasive isolates. In conclusion, Bifidobacterium has an invasive potential in
the immunocompromised host and may cause a sepsis-like picture. Using comparative
genomics, we could not delineate specific pathogenicity traits characterizing
invasive isolates.
PMID- 28490489
TI - A Single Negative Result for van Quantitative PCR on Enrichment Broth Can Replace
Five Rectal Swab Cultures in Screening for Vancomycin-Resistant Enterococci.
AB - The increased incidence of infections by vancomycin-resistant Enterococcus (VRE)
causes an accumulation of patients who are either colonized with VRE or flagged
as potentially colonized with VRE. Since such patients require precautionary
isolation upon admission to a hospital, rapid methods to establish VRE
colonization status would improve patient care and optimize hospital operation.
We evaluated van quantitative PCR (qPCR) on one enrichment broth as a VRE
screening approach. We obtained 255 sets of five rectal specimens from 243
patients. The specimens were cultured using an amoxicillin-containing enrichment
broth. Subsequently, a chromogenic agar was incubated and suspect colonies were
inoculated on a blood agar plate and characterized by matrix-assisted laser
desorption ionization-time of flight (MALDI-TOF), followed by a vancomycin Etest
in cases in which Enterococcus spp. were detected. The culturing results were
compared with the outcome of van qPCR on all enrichment broths of the first
rectal swab. The van qPCR was positive for 43% of the sample sets (vanA, n = 5;
vanB, n = 101; vanA and vanB, n = 3). Based on culture data, 20 (7.8%) of the
sets were VRE positive in at least one of five samples. The negative predictive
value of van qPCR on the first enrichment broth was 99.3%. With a cutoff
quantification cycle (Cq ) value of >35 to discriminate negative and positive
samples, 87% of the negative patients can be identified within a day after
obtaining the sample, compared to 7 days in the culturing approach. VRE screening
using qPCR on one enrichment broth can quickly identify non-VRE-colonized
patients and therefore decrease costs and limit unnecessary isolation
restrictions.
PMID- 28490488
TI - Genetic and Epidemiologic Trends of Norovirus Outbreaks in the United States from
2013 to 2016 Demonstrated Emergence of Novel GII.4 Recombinant Viruses.
AB - Noroviruses are the most frequent cause of epidemic acute gastroenteritis in the
United States. Between September 2013 and August 2016, 2,715 genotyped norovirus
outbreaks were submitted to CaliciNet. GII.4 Sydney viruses caused 58% of the
outbreaks during these years. A GII.4 Sydney virus with a novel GII.P16
polymerase emerged in November 2015, causing 60% of all GII.4 outbreaks in the
2015-2016 season. Several genotypes detected were associated with more than one
polymerase type, including GI.3, GII.2, GII.3, GII.4 Sydney, GII.13, and GII.17,
four of which harbored GII.P16 polymerases. GII.P16 polymerase sequences
associated with GII.2 and GII.4 Sydney viruses were nearly identical, suggesting
common ancestry. Other common genotypes, each causing 5 to 17% of outbreaks in a
season, included GI.3, GI.5, GII.2, GII.3, GII.6, GII.13, and GII.17 Kawasaki
308. Acquisition of alternative RNA polymerases by recombination is an important
mechanism for norovirus evolution and a phenomenon that was shown to occur more
frequently than previously recognized in the United States. Continued molecular
surveillance of noroviruses, including typing of both polymerase and capsid
genes, is important for monitoring emerging strains in our continued efforts to
reduce the overall burden of norovirus disease.
PMID- 28490490
TI - Analysis of Morphologically Similar Staphylococcus aureus Colonies for Assessment
of Phenotypic and Genotypic Correlation.
PMID- 28490491
TI - Comparison of the Vitek MS and Bruker Matrix-Assisted Laser Desorption Ionization
Time of Flight Mass Spectrometry Systems for Identification of Rhodococcus equi
and Dietzia spp.
AB - Rhodococcus equi causes pyogranulomatous pneumonia in domesticated animals and
immunocompromised humans. Dietzia spp. are environmental bacteria that have
rarely been associated with human infections. R. equi and Dietzia spp. are
closely related actinomycetes. Phenotypic discrimination between R. equi and
Dietzia on the basis of their Gram stain morphology and colony appearance is
problematic. Matrix-assisted laser desorption ionization-time of flight mass
spectrometry (MALDI-TOF MS) is a fast, reliable, and cost-effective method for
identification of a wide variety of microorganisms. We have evaluated the
performance of Bruker Biotyper versus that of Vitek MS for identification of a
collection of 154 isolates identified at the source as R. equi that includes
isolates belonging to the genus Dietzia PCR amplification of the choE gene,
encoding a cholesterol oxidase, and 16S rRNA sequencing were considered the
reference methods for R. equi identification. Biotyper identified 131 (85.1%) of
the 154 isolates at the species level, and this figure increased to 152 (98.7%)
when the species cutoff was reduced from a score of >=2.000 to >=1.750. Vitek MS
correctly identified at the species level 130 (84.4%) isolates as long as
bacteria were extracted with ethanol but only 35 (22.7%) isolates when samples
were prepared by direct extraction from colonies. The two systems allowed
differentiation between R. equi and Dietzia spp., but identification of all
Dietzia sp. isolates at the species level needed sequencing of the 16S rRNA gene.
PMID- 28490492
TI - Molecular Diagnosis of Orthopedic-Device-Related Infection Directly from
Sonication Fluid by Metagenomic Sequencing.
AB - Culture of multiple periprosthetic tissue samples is the current gold standard
for microbiological diagnosis of prosthetic joint infections (PJI). Additional
diagnostic information may be obtained through culture of sonication fluid from
explants. However, current techniques can have relatively low sensitivity, with
prior antimicrobial therapy and infection by fastidious organisms influencing
results. We assessed if metagenomic sequencing of total DNA extracts obtained
direct from sonication fluid can provide an alternative rapid and sensitive tool
for diagnosis of PJI. We compared metagenomic sequencing with standard aerobic
and anaerobic culture in 97 sonication fluid samples from prosthetic joint and
other orthopedic device infections. Reads from Illumina MiSeq sequencing were
taxonomically classified using Kraken. Using 50 derivation samples, we determined
optimal thresholds for the number and proportion of bacterial reads required to
identify an infection and confirmed our findings in 47 independent validation
samples. Compared to results from sonication fluid culture, the species-level
sensitivity of metagenomic sequencing was 61/69 (88%; 95% confidence interval
[CI], 77 to 94%; for derivation samples 35/38 [92%; 95% CI, 79 to 98%]; for
validation samples, 26/31 [84%; 95% CI, 66 to 95%]), and genus-level sensitivity
was 64/69 (93%; 95% CI, 84 to 98%). Species-level specificity, adjusting for
plausible fastidious causes of infection, species found in concurrently obtained
tissue samples, and prior antibiotics, was 85/97 (88%; 95% CI, 79 to 93%; for
derivation samples, 43/50 [86%; 95% CI, 73 to 94%]; for validation samples, 42/47
[89%; 95% CI, 77 to 96%]). High levels of human DNA contamination were seen
despite the use of laboratory methods to remove it. Rigorous laboratory good
practice was required to minimize bacterial DNA contamination. We demonstrate
that metagenomic sequencing can provide accurate diagnostic information in PJI.
Our findings, combined with the increasing availability of portable, random
access sequencing technology, offer the potential to translate metagenomic
sequencing into a rapid diagnostic tool in PJI.
PMID- 28490493
TI - Problems with the Oxford Multilocus Sequence Typing Scheme for Acinetobacter
baumannii: Do Sequence Type 92 (ST92) and ST109 Exist?
PMID- 28490494
TI - Structural basis for spumavirus GAG tethering to chromatin.
AB - The interactions between a retrovirus and host cell chromatin that underlie
integration and provirus expression are poorly understood. The prototype foamy
virus (PFV) structural protein GAG associates with chromosomes via a chromatin
binding sequence (CBS) located within its C-terminal region. Here, we show that
the PFV CBS is essential and sufficient for a direct interaction with nucleosomes
and present a crystal structure of the CBS bound to a mononucleosome. The CBS
interacts with the histone octamer, engaging the H2A-H2B acidic patch in a manner
similar to other acidic patch-binding proteins such as herpesvirus latency
associated nuclear antigen (LANA). Substitutions of the invariant arginine anchor
residue in GAG result in global redistribution of PFV and macaque simian foamy
virus (SFVmac) integration sites toward centromeres, dampening the resulting
proviral expression without affecting the overall efficiency of integration. Our
findings underscore the importance of retroviral structural proteins for
integration site selection and the avoidance of genomic junkyards.
PMID- 28490496
TI - Correction for Zastrow, News Feature: Is video game addiction really an
addiction?
PMID- 28490495
TI - Exclusion of alternative exon 33 of CaV1.2 calcium channels in heart is
proarrhythmogenic.
AB - Alternative splicing changes the CaV1.2 calcium channel electrophysiological
property, but the in vivo significance of such altered channel function is
lacking. Structure-function studies of heterologously expressed CaV1.2 channels
could not recapitulate channel function in the native milieu of the
cardiomyocyte. To address this gap in knowledge, we investigated the role of
alternative exon 33 of the CaV1.2 calcium channel in heart function. Exclusion of
exon 33 in CaV1.2 channels has been reported to shift the activation potential
10.4 mV to the hyperpolarized direction, and increased expression of
CaV1.2Delta33 channels was observed in rat myocardial infarcted hearts. However,
how a change in CaV1.2 channel electrophysiological property, due to alternative
splicing, might affect cardiac function in vivo is unknown. To address these
questions, we generated mCacna1c exon 33-/--null mice. These mice contained
CaV1.2Delta33 channels with a gain-of-function that included conduction of larger
currents that reflects a shift in voltage dependence and a modest increase in
single-channel open probability. This altered channel property underscored the
development of ventricular arrhythmia, which is reflected in significantly more
deaths of exon 33-/- mice from beta-adrenergic stimulation. In vivo telemetric
recordings also confirmed increased frequencies in premature ventricular
contractions, tachycardia, and lengthened QT interval. Taken together, the
significant decrease or absence of exon 33-containing CaV1.2 channels is
potentially proarrhythmic in the heart. Of clinical relevance, human ischemic and
dilated cardiomyopathy hearts showed increased inclusion of exon 33. However, the
possible role that inclusion of exon 33 in CaV1.2 channels may play in the
pathogenesis of human heart failure remains unclear.
PMID- 28490497
TI - Protein composition of the hepatitis A virus quasi-envelope.
AB - The Picornaviridae are a diverse family of RNA viruses including many pathogens
of medical and veterinary importance. Classically considered "nonenveloped,"
recent studies show that some picornaviruses, notably hepatitis A virus (HAV;
genus Hepatovirus) and some members of the Enterovirus genus, are released from
cells nonlytically in membranous vesicles. To better understand the biogenesis of
quasi-enveloped HAV (eHAV) virions, we conducted a quantitative proteomics
analysis of eHAV purified from cell-culture supernatant fluids by isopycnic
ultracentrifugation. Amino acid-coded mass tagging (AACT) with stable isotopes
followed by tandem mass spectrometry sequencing and AACT quantitation of peptides
provided unambiguous identification of proteins associated with eHAV versus
unrelated extracellular vesicles with similar buoyant density. Multiple peptides
were identified from HAV capsid proteins (53.7% coverage), but none from
nonstructural proteins, indicating capsids are packaged as cargo into eHAV
vesicles via a highly specific sorting process. Other eHAV-associated proteins (n
= 105) were significantly enriched for components of the endolysosomal system
(>60%, P < 0.001) and included many common exosome-associated proteins such as
the tetraspanin CD9 and dipeptidyl peptidase 4 (DPP4) along with multiple
endosomal sorting complex required for transport III (ESCRT-III)-associated
proteins. Immunoprecipitation confirmed that DPP4 is displayed on the surface of
eHAV produced in cell culture or present in sera from humans with acute hepatitis
A. No LC3-related peptides were identified by mass spectrometry. RNAi depletion
studies confirmed that ESCRT-III proteins, particularly CHMP2A, function in eHAV
biogenesis. In addition to identifying surface markers of eHAV vesicles, the
results support an exosome-like mechanism of eHAV egress involving endosomal
budding of HAV capsids into multivesicular bodies.
PMID- 28490498
TI - Shelterin components mediate genome reorganization in response to replication
stress.
AB - The dynamic nature of genome organization impacts critical nuclear functions
including the regulation of gene expression, replication, and DNA damage repair.
Despite significant progress, the mechanisms responsible for reorganization of
the genome in response to cellular stress, such as aberrant DNA replication, are
poorly understood. Here, we show that fission yeast cells carrying a mutation in
the DNA-binding protein Sap1 show defects in DNA replication progression and
genome stability and display extensive changes in genome organization.
Chromosomal regions such as subtelomeres that show defects in replication
progression associate with the nuclear envelope in sap1 mutant cells. Moreover,
high-resolution, genome-wide chromosome conformation capture (Hi-C) analysis
revealed prominent contacts between telomeres and chromosomal arm regions
containing replication origins proximal to binding sites for Taz1, a component of
the Shelterin telomere protection complex. Strikingly, we find that Shelterin
components are required for interactions between Taz1-associated chromosomal arm
regions and telomeres. These analyses reveal an unexpected role for Shelterin
components in genome reorganization in cells experiencing replication stress,
with important implications for understanding the mechanisms governing
replication and genome stability.
PMID- 28490499
TI - Development of an optimized synthetic Notch receptor as an in vivo cell-cell
contact sensor.
AB - Detection and manipulation of direct cell-cell contact in complex tissues is a
fundamental and challenging problem in many biological studies. Here, we report
an optimized Notch-based synthetic receptor (synNQ) useful to study direct cell
cell interactions in Drosophila With the synNQ system, cells expressing a
synthetic receptor, which contains Notch activation machinery and a downstream
transcriptional activator, QF, are activated by a synthetic GFP ligand expressed
by contacting neighbor cells. To avoid cis-inhibition, mutually exclusive
expression of the synthetic ligand and receptor is achieved using the "flippase
out" system. Expression of the synthetic GFP ligand is controlled by the Gal4/UAS
system for easy and broad applications. Using synNQ, we successfully visualized
cell-cell interactions within and between most fly tissues, revealing previously
undocumented cell-cell contacts. Importantly, in addition to detection of cells
in contact with one another, synNQ allows for genetic manipulation in all cells
in contact with a targeted cell population, which we demonstrate in the context
of cell competition in developing wing disks. Altogether, the synNQ genetic
system will enable a broad range of studies of cell contact in developmental
biology.
PMID- 28490500
TI - The wisdom of crowds for visual search.
AB - Decision-making accuracy typically increases through collective integration of
people's judgments into group decisions, a phenomenon known as the wisdom of
crowds. For simple perceptual laboratory tasks, classic signal detection theory
specifies the upper limit for collective integration benefits obtained by
weighted averaging of people's confidences, and simple majority voting can often
approximate that limit. Life-critical perceptual decisions often involve
searching large image data (e.g., medical, security, and aerial imagery), but the
expected benefits and merits of using different pooling algorithms are unknown
for such tasks. Here, we show that expected pooling benefits are significantly
greater for visual search than for single-location perceptual tasks and the
prediction given by classic signal detection theory. In addition, we show that
simple majority voting obtains inferior accuracy benefits for visual search
relative to averaging and weighted averaging of observers' confidences. Analysis
of gaze behavior across observers suggests that the greater collective
integration benefits for visual search arise from an interaction between the
foveated properties of the human visual system (high foveal acuity and low
peripheral acuity) and observers' nonexhaustive search patterns, and can be
predicted by an extended signal detection theory framework with trial to trial
sampling from a varying mixture of high and low target detectabilities across
observers (SDT-MIX). These findings advance our theoretical understanding of how
to predict and enhance the wisdom of crowds for real world search tasks and could
apply more generally to any decision-making task for which the minority of group
members with high expertise varies from decision to decision.
PMID- 28490501
TI - Dynamic microtubules regulate cellular contractility during T-cell activation.
AB - T-cell receptor (TCR) triggering and subsequent T-cell activation are essential
for the adaptive immune response. Recently, multiple lines of evidence have shown
that force transduction across the TCR complex is involved during TCR triggering,
and that the T cell might use its force-generation machinery to probe the
mechanical properties of the opposing antigen-presenting cell, giving rise to
different signaling and physiological responses. Mechanistically, actin
polymerization and turnover have been shown to be essential for force generation
by T cells, but how these actin dynamics are regulated spatiotemporally remains
poorly understood. Here, we report that traction forces generated by T cells are
regulated by dynamic microtubules (MTs) at the interface. These MTs suppress Rho
activation, nonmuscle myosin II bipolar filament assembly, and actin retrograde
flow at the T-cell-substrate interface. Our results suggest a novel role of the
MT cytoskeleton in regulating force generation during T-cell activation.
PMID- 28490502
TI - Evidence from Fermi surface analysis for the low-temperature structure of
lithium.
AB - The low-temperature crystal structure of elemental lithium, the prototypical
simple metal, is a several-decades-old problem. At 1 atm pressure and 298 K, Li
forms a body-centered cubic lattice, which is common to all alkali metals.
However, a low-temperature phase transition was experimentally detected to a
structure initially identified as having the 9R stacking. This structure,
proposed by Overhauser in 1984, has been questioned repeatedly but has not been
confirmed. Here we present a theoretical analysis of the Fermi surface of lithium
in several relevant structures. We demonstrate that experimental measurements of
the Fermi surface based on the de Haas-van Alphen effect can be used as a
diagnostic method to investigate the low-temperature phase diagram of lithium.
This approach may overcome the limitations of X-ray and neutron diffraction
techniques and makes possible, in principle, the determination of the lithium low
temperature structure (and that of other metals) at both ambient and high
pressure. The theoretical results are compared with existing low-temperature
ambient pressure experimental data, which are shown to be inconsistent with a 9R
phase for the low-temperature structure of lithium.
PMID- 28490503
TI - Entropic forces drive self-organization and membrane fusion by SNARE proteins.
AB - SNARE proteins are the core of the cell's fusion machinery and mediate virtually
all known intracellular membrane fusion reactions on which exocytosis and
trafficking depend. Fusion is catalyzed when vesicle-associated v-SNAREs form
trans-SNARE complexes ("SNAREpins") with target membrane-associated t-SNAREs, a
zippering-like process releasing ~65 kT per SNAREpin. Fusion requires several
SNAREpins, but how they cooperate is unknown and reports of the number required
vary widely. To capture the collective behavior on the long timescales of fusion,
we developed a highly coarse-grained model that retains key biophysical SNARE
properties such as the zippering energy landscape and the surface charge
distribution. In simulations the ~65-kT zippering energy was almost entirely
dissipated, with fully assembled SNARE motifs but uncomplexed linker domains. The
SNAREpins self-organized into a circular cluster at the fusion site, driven by
entropic forces that originate in steric-electrostatic interactions among
SNAREpins and membranes. Cooperative entropic forces expanded the cluster and
pulled the membranes together at the center point with high force. We find that
there is no critical number of SNAREs required for fusion, but instead the fusion
rate increases rapidly with the number of SNAREpins due to increasing entropic
forces. We hypothesize that this principle finds physiological use to boost
fusion rates to meet the demanding timescales of neurotransmission, exploiting
the large number of v-SNAREs available in synaptic vesicles. Once in an
unfettered cluster, we estimate >=15 SNAREpins are required for fusion within the
~1-ms timescale of neurotransmitter release.
PMID- 28490504
TI - Fasciculation in amyotrophic lateral sclerosis: origin and pathophysiological
relevance.
AB - This review considers the origin and significance of fasciculations in
neurological practice, with an emphasis on fasciculations in amyotrophic lateral
sclerosis (ALS), and in benign fasciculation syndromes. Fasciculation represents
a brief spontaneous contraction that affects a small number of muscle fibres,
causing a flicker of movement under the skin. While an understanding of the role
of fasciculation in ALS remains incomplete, fasciculations derive from ectopic
activity generated in the motor system. A proximal origin seems likely to
contribute to the generation of fasciculation in the early stages of ALS, while
distal sites of origin become more prominent later in the disease, associated
with distal motor axonal sprouting as part of the reinnervation response that
develops secondary to loss of motor neurons. Fasciculations are distinct from the
recurrent trains of axonal firing described in neuromyotonia. Fasciculation
without weakness, muscle atrophy or increased tendon reflexes suggests a benign
fasciculation syndrome, even when of sudden onset. Regardless of origin,
fasciculations often present as the initial abnormality in ALS, an early
harbinger of dysfunction and aberrant firing of motor neurons.
PMID- 28490505
TI - Application of the CSF JCV antibody index to early natalizumab-associated
progressive multifocal leukoencephalopathy.
PMID- 28490506
TI - Polyadenylation is the key aspect of GLD-2 function in C. elegans.
AB - The role of many enzymes extends beyond their dedicated catalytic activity by
fulfilling important cellular functions in a catalysis-independent fashion. In
this aspect, little is known about 3'-end RNA-modifying enzymes that belong to
the class of nucleotidyl transferases. Among these are noncanonical poly(A)
polymerases, a group of evolutionarily conserved enzymes that are critical for
gene expression regulation, by adding adenosines to the 3'-end of RNA targets. In
this study, we investigate whether the functions of the cytoplasmic poly(A)
polymerase (cytoPAP) GLD-2 in C. elegans germ cells exclusively depend on its
catalytic activity. To this end, we analyzed a specific missense mutation
affecting a conserved amino acid in the catalytic region of GLD-2 cytoPAP.
Although this mutated protein is expressed to wild-type levels and incorporated
into cytoPAP complexes, we found that it cannot elongate mRNA poly(A) tails
efficiently or promote GLD-2 target mRNA abundance. Furthermore, germ cell
defects in animals expressing this mutant protein strongly resemble those lacking
the GLD-2 protein altogether, arguing that only the polyadenylation activity of
GLD-2 is essential for gametogenesis. In summary, we propose that all known
molecular and biological functions of GLD-2 depend on its enzymatic activity,
demonstrating that polyadenylation is the key mechanism of GLD-2 functionality.
Our findings highlight the enzymatic importance of noncanonical poly(A)
polymerases and emphasize the pivotal role of poly(A) tail-centered cytoplasmic
mRNA regulation in germ cell biology.
PMID- 28490508
TI - Longer exposure to a new refugee food ration is associated with reduced
prevalence of small for gestational age: results from 2 cross-sectional surveys
on the Thailand-Myanmar border.
AB - Background: Despite the high risk of compromised nutrition, evidence of the
effect of refugee rations on fetal growth is limited. A new ration containing
micronutrient-fortified flour without increased caloric content of the general
food basket was introduced to the Maela refugee camp in Thailand, July
2004.Objective: The effect of the length of gestational exposure of the new
ration on fetal growth was compared with birth outcomes [small for gestational
age (SGA), preterm birth (PTB)].Design: In an observational study in 987 newborns
from 1048 prospectively followed antenatal clinic (ANC) attendees enrolled in 2
cross-sectional surveys, exposure was categorized in 2004 according to gestation
at the time of commencing the new ration and in 2006 as comprehensive
(preconception and pregnancy). In both surveys, the pregnancy-specific ration and
vitamin supplements were routine.Results: In 2004, the proportions of SGA
decreased with longer exposure to the new ration: no exposure during pregnancy
(27.7%; n = 13 of 47) and exposure in the third (27.6%; n = 37 of 134), second
(18.6%; n = 35 of 188), and first (19.4%; n = 6 of 31) trimesters, respectively
(adjusted P-trend = 0.046). In 2006, the new ration was available to all women
and there was no significant additional impact of the pregnancy-specific ration
and vitamin supplements. Between 2004 and 2006, SGA decreased from 28.9% (13 of
45) to 17.3% (69 of 398) (adjusted P = 0.050), a reduction of 40.1% (95% CI:
34.7%, 45.9%); there was also a decrease in the percentage of underweight women
on admission to the ANC (38.2%; 95% CI: 31.4%, 45.5%). PTB rates were low and not
significantly different with exposure to the new ration.Conclusions: In 2004, the
earlier in gestation in which the new ration was available the greater the effect
on fetal growth as shown by a reduced prevalence of SGA. In 2006, additional
benefits to fetal growth from the pregnancy-specific ration and vitamin
supplements beyond those of the preconception ration were not observed. Good
nutrition in pregnancy remains an important challenge for refugee populations.
This trial was registered at http://drks-neu.uniklinik-freiburg.de/drks_web/ as
DRKS00007736.
PMID- 28490509
TI - Vitamin D and calcium intake and risk of early menopause.
AB - Background: Early menopause, defined as the cessation of ovarian function before
the age of 45 y, affects ~10% of women and is associated with higher risk of
cardiovascular disease, osteoporosis, and other conditions. Few modifiable risk
factors for early menopause have been identified, but emerging data suggest that
high vitamin D intake may reduce risk.Objective: We evaluated how intakes of
vitamin D and calcium are associated with the incidence of early menopause in the
prospective Nurses' Health Study II (NHS2).Design: Intakes of vitamin D and
calcium from foods and supplements were measured every 4 y with the use of a food
frequency questionnaire. Cases of incident early menopause were identified from
all participants who were premenopausal at baseline in 1991; over 1.13 million
person-years, 2041 women reported having natural menopause before the age of 45
y. We used Cox proportional hazards regression to evaluate relations between
intakes of vitamin D and calcium and incident early menopause while accounting
for potential confounding factors.Results: After adjustment for age, smoking, and
other factors, women with the highest intake of dietary vitamin D (quintile
median: 528 IU/d) had a significant 17% lower risk of early menopause than women
with the lowest intake [quintile median: 148 IU/d; HR: 0.83 (95% CI: 0.72, 0.95);
P-trend = 0.03]. Dietary calcium intake in the highest quintile (median: 1246
mg/d) compared with the lowest (median: 556 mg/d) was associated with a
borderline significantly lower risk of early menopause (HR: 0.87; 95% CI: 0.76,
1.00; P-trend = 0.03). Associations were stronger for vitamin D and calcium from
dairy sources than from nondairy dietary sources, whereas high supplement use was
not associated with lower risk.Conclusions: Findings suggest that high intakes of
dietary vitamin D and calcium may be modestly associated with a lower risk of
early menopause. Further studies evaluating 25-hydroxyvitamin D concentrations,
other dairy constituents, and early menopause are warranted.
PMID- 28490510
TI - Nonfermented milk and other dairy products: associations with all-cause
mortality.
AB - Background: A positive association between nonfermented milk intake and increased
all-cause mortality was recently reported, but overall, the association between
dairy intake and mortality is inconclusive.Objective: We studied associations
between intake of dairy products and all-cause mortality with an emphasis on
nonfermented milk and fat content.Design: A total of 103,256 adult participants
(women: 51.0%) from Northern Sweden were included (7121 deaths; mean follow-up:
13.7 y). Associations between all-cause mortality and reported intakes of
nonfermented milk (total or by fat content), fermented milk, cheese, and butter
were tested with the use of Cox proportional hazards models that were adjusted
for age, sex, body mass index, smoking status, education, energy intake,
examination year, and physical activity. To circumvent confounding, Mendelian
randomization was applied in a subsample via the lactase LCT-13910 C/T single
nucleotide polymorphism that is associated with lactose tolerance and milk
intake.Results: High consumers of nonfermented milk (>=2.5 times/d) had a 32%
increased hazard (HR: 1.32; 95% CI: 1.18, 1.48) for all-cause mortality compared
with that of subjects who consumed milk <=1 time/wk. The corresponding value for
butter was 11% (HR: 1.11; 95% CI: 1.07, 1.21). All nonfermented milk-fat types
were independently associated with increased HRs, but compared with full-fat
milk, HRs were lower in consumers of medium- and low-fat milk. Fermented milk
intake (HR: 0.90; 95% CI: 0.86, 0.94) and cheese intake (HR: 0.93; 95% CI: 0.91,
0.96) were negatively associated with mortality. Results were slightly attenuated
by lifestyle adjustments but were robust in sensitivity analyses. Mortality was
not significantly associated with the LCT-13910 C/T genotype in the smaller
subsample. The amount and type of milk intake was associated with lifestyle
variables.Conclusions: In the present Swedish cohort study, intakes of
nonfermented milk and butter are associated with higher all-cause mortality, and
fermented milk and cheese intakes are associated with lower all-cause mortality.
Residual confounding by lifestyle cannot be excluded, and Mendelian randomization
needs to be examined in a larger sample.
PMID- 28490511
TI - Impact of breakfast skipping compared with dinner skipping on regulation of
energy balance and metabolic risk.
AB - Background: Meal skipping has become an increasing trend of the modern lifestyle
that may lead to obesity and type 2 diabetes.Objective: We investigated whether
the timing of meal skipping impacts these risks by affecting circadian regulation
of energy balance, glucose metabolism, and postprandial inflammatory
responses.Design: In a randomized controlled crossover trial, 17 participants
[body mass index (in kg/m2): 23.7 +/- 4.6] underwent 3 isocaloric 24-h
interventions (55%, 30%, and 15% carbohydrate, fat, and protein, respectively): a
breakfast skipping day (BSD) and a dinner skipping day (DSD) separated by a
conventional 3-meal-structure day (control). Energy and macronutrient balance was
measured in a respiration chamber. Postprandial glucose, insulin, and
inflammatory responses in leukocytes as well as 24-h glycemia and insulin
secretion were analyzed.Results: When compared with the 3-meal control, 24-h
energy expenditure was higher on both skipping days (BSD: +41 kcal/d; DSD: +91
kcal/d; both P < 0.01), whereas fat oxidation increased on the BSD only (+16 g/d;
P < 0.001). Spontaneous physical activity, 24-h glycemia, and 24-h insulin
secretion did not differ between intervention days. The postprandial homeostasis
model assessment index (+54%) and glucose concentrations after lunch (+46%) were,
however, higher on the BSD than on the DSD (both P < 0.05). Concomitantly, a
longer fasting period with breakfast skipping also increased the inflammatory
potential of peripheral blood cells after lunch.Conclusions: Compared with 3
meals/d, meal skipping increased energy expenditure. In contrast, higher
postprandial insulin concentrations and increased fat oxidation with breakfast
skipping suggest the development of metabolic inflexibility in response to
prolonged fasting that may in the long term lead to low-grade inflammation and
impaired glucose homeostasis. This trial was registered at clinicaltrials.gov as
NCT02635139.
PMID- 28490512
TI - Preconceptional and gestational weight trajectories and risk of delivering a
small-for-gestational-age baby in rural Gambia.
AB - Background: Maternal nutritional status is a key determinant of small for
gestational age (SGA), but some knowledge gaps remain, particularly regarding the
role of the energy balance entering pregnancy.Objective: We investigated how
preconceptional and gestational weight trajectories (summarized by individual
level traits) are associated with SGA risk in rural Gambia.Design: The sample
comprised 670 women in a trial with serial weight data (7310 observations) that
were available before and during pregnancy. Individual trajectories from 6 mo
before conception to 30 wk of gestation were produced with the use of multilevel
modeling. Summary traits were expressed as weight z scores [weight z score at 3
mo preconception (zwt-3 mo), weight z score at conception, weight z score at 3 mo
postconception, weight z score at 7 mo postconception (zwt+7 mo), and conditional
measures that represented the change from the preceding time] and were related to
SGA risk with the use of Poisson regression with confounder adjustment; linear
splines were used to account for nonlinearity.Results: Maternal weight at each
time point had a consistent nonlinear relation with SGA risk. For example, the
zwt-3 mo estimate was stronger in women with values <=0.5 (RR: 0.736; 95% CI:
0.594, 0.910) than in women with values >0.5 (RR: 0.920; 95% CI: 0.682, 1.241).
The former group had the highest observed SGA prevalence. Focusing on weight
change, only conditional zwt+7 mo was associated with SGA and only in women with
values >-0.5 (RR: 0.579; 95% CI: 0.463, 0.724).Conclusions: Protection against
delivering an SGA neonate offered by greater preconceptional or gestational
weight may be most pronounced in more undernourished and vulnerable women.
Independent of this possibility, greater second- and third-trimester weight gain
beyond a threshold may be protective. This trial was registered at
http://www.isrctn.com/ as ISRCTN49285450.
PMID- 28490513
TI - Effect of maternal antenatal and newborn supplementation with vitamin A on
cognitive development of school-aged children in rural Bangladesh: a follow-up of
a placebo-controlled, randomized trial.
AB - Background: The impact of early vitamin A supplementation on neurodevelopmental
function has not been adequately studied. In rural Bangladesh we examined
cognitive and motor function and scholastic achievement in a cohort of children
who were exposed to vitamin A in utero or at birth.Objective: The aim of this
study was to examine independent and combined effects of antenatal and newborn
supplementation with vitamin A on the cognitive function of children at 8 y of
age.Design: A cohort of rural Bangladeshi children from 2 previous double-blind,
placebo-controlled cluster-randomized trials were revisited at age 8 y between
February 2013 and June 2014. Data on sociodemographic, social, and physical
conditions; schooling; child care behavior; anthropometric measures; and
cognitive function were collected with the use of various psychometric assessment
tools.Results: Among 11,950 children from the parent trial who were last known to
be alive, a subset of 1803 children balanced by treatment group in a selected
contiguous study area were re-enrolled and 1613 (89%) provided consent for
assessments. Of these, 1577 (87%) children had a complete cognitive evaluation.
All groups were highly comparable on baseline variables collected in the previous
trials and factors measured at re-enrollment. Overall, there was no impact of
either maternal or newborn supplementation with vitamin A on intelligence,
memory, and motor function. Compared with placebo, children who received both
interventions had significantly better performance in reading, spelling, and math
computation, with increased mean (95% CI) scores of 8.0 (2.2, 13.8), 6.8 (1.9,
11.7), and 4.8 (0.6, 9.0), respectively.Conclusions: General intelligence or
memory and motor functions were not affected by antenatal or newborn
supplementation with vitamin A. Scholastic performance and aspects of executive
function improved when both interventions were provided. These trials were
registered at clinicaltrials.gov as NCT00198822 and NCT00128557.
PMID- 28490514
TI - Vitamin D supplementation has no effect on insulin sensitivity or secretion in
vitamin D-deficient, overweight or obese adults: a randomized placebo-controlled
trial.
AB - Background: Vitamin D supplementation has been proposed as a potential strategy
to prevent type 2 diabetes. Existing clinical trials have been limited by short
duration, low doses of vitamin D, variability in participants' vitamin D
deficiency status, and the use of surrogate measures of body composition, insulin
sensitivity, and insulin secretion.Objective: To address existing knowledge gaps,
we conducted a double-blind, randomized, placebo-controlled trial to investigate
whether vitamin D supplementation that is provided in a sufficient dose and
duration to vitamin D-deficient individuals would improve insulin sensitivity or
secretion as measured with the use of gold-standard methods. We hypothesized that
vitamin D supplementation would improve insulin sensitivity and secretion
compared with placebo.Design: Sixty-five overweight or obese, vitamin D-deficient
(25-hydroxyvitamin D [25(OH)D] concentration <=50 nmol/L) adults were randomly
assigned to receive either a bolus oral dose of 100,000 IU cholecalciferol
followed by 4000 IU cholecalciferol/d or a matching placebo for 16 wk. Before and
after the intervention, participants received gold-standard assessments of body
composition (via dual X-ray absorptiometry), insulin sensitivity (via
hyperinsulinemic-euglycemic clamps), and insulin secretion [via intravenous
glucose-tolerance tests (IVGTTs)].Results: Fifty-four participants completed the
study [35 men and 19 women; mean +/- SD age: 31.9 +/- 8.5 y; body mass index (in
kg/m2): 30.9 +/- 4.4]. 25(OH)D increased with vitamin D supplementation compared
with placebo (57.0 +/- 21.3 compared with 1.9 +/- 15.1 nmol/L, respectively; P =
0.02). Vitamin D and placebo groups did not differ in change in insulin
sensitivity (0.02 +/- 2.0 compared with -0.03 +/- 2.8 mg . kg-1 . min-1,
respectively; P = 0.9) or first-phase insulin secretion (-21 +/- 212 compared
with 24 +/- 184 mU/L, respectively; P = 0.9). Results remained nonsignificant
after adjustment for age, sex, percentage of body fat, sun exposure, physical
activity, and dietary vitamin D intake (P > 0.1).Conclusions: Vitamin D
supplementation does not improve insulin sensitivity or secretion in vitamin D
deficient, overweight or obese adults, despite using high-dose vitamin D
supplementation and robust endpoint measures. Therefore, it is unlikely that
vitamin D supplementation would be an effective strategy for reducing diabetes
risk even in vitamin D-deficient populations. This trial was registered at
clinicaltrials.gov as NCT02112721.
PMID- 28490515
TI - The effect of oral iron with or without multiple micronutrients on hemoglobin
concentration and hemoglobin response among nonpregnant Cambodian women of
reproductive age: a 2 x 2 factorial, double-blind, randomized controlled
supplementation trial.
AB - Background: Despite a high prevalence of anemia among nonpregnant Cambodian
women, current reports suggest that iron deficiency (ID) prevalence is low. If
true, iron supplementation will not be an effective anemia reduction
strategy.Objective: We measured the effect of daily oral iron with or without
multiple micronutrients (MMNs) on hemoglobin concentration in nonpregnant
Cambodian women screened as anemic.Design: In this 2 * 2 factorial, double-blind,
randomized trial, nonpregnant women (aged 18-45 y) with hemoglobin concentrations
<=117 g/L (capillary blood) were recruited from 26 villages in Kampong Chhnang
province and randomly assigned to receive 12 wk of iron (60 mg; Fe group), MMNs
(14 other micronutrients; MMN group), iron plus MMNs (Fe+MMN group), or placebo
capsules. A 2 * 2 factorial intention-to-treat analysis with the use of a
generalized mixed-effects model was used to assess the effects of iron and MMNs
and the interaction between these factors. Results: In July 2015, 809 women were
recruited and 760 (94%) completed the trial. Baseline anemia prevalence was 58%
(venous blood). Mean (95% CI) hemoglobin concentrations at 12 wk in the Fe, MMN,
Fe+MMN, and placebo groups were 121 (120, 121), 116 (116, 117), 123 (122, 123),
and 116 (116, 117) g/L, with no iron * MMN interaction (P = 0.66). Mean (95% CI)
increases in hemoglobin were 5.6 g/L (3.8, 7.4 g/L) (P < 0.001) among women who
received iron (n = 407) and 1.2 g/L (-0.6, 3.0 g/L) (P = 0.18) among women who
received MMNs (n = 407). The predicted proportions (95% CIs) of women with a
hemoglobin response (>=10 g/L at 12 wk) were 19% (14%, 24%), 9% (5%, 12%), 30%
(24%, 35%), and 5% (2%, 9%) in the Fe, MMN, Fe+MMN, and placebo groups,
respectively.Conclusions: Daily iron supplementation for 12 wk increased
hemoglobin in nonpregnant Cambodian women; however, MMNs did not confer
additional significant benefit. Overall, ~24% of women who received iron
responded after 12 wk; even fewer would be likely to respond in the wider
population. This trial was registered at clinicaltrials.gov as NCT02481375.
PMID- 28490516
TI - The positive impact of general vitamin D food fortification policy on vitamin D
status in a representative adult Finnish population: evidence from an 11-y follow
up based on standardized 25-hydroxyvitamin D data.
AB - Background: A systematic vitamin D fortification of fluid milk products and fat
spreads was started in 2003 in Finland to improve vitamin D status. Objective: We
investigated the effects of the vitamin D fortification policy on vitamin D
status in Finland between 2000 and 2011.Design: Serum 25-hydroxyvitamin D [S
25(OH)D] concentrations of a nationally representative sample comprising 6134 and
4051 adults aged >=30 y from the Health 2000 and Health 2011 surveys,
respectively, were standardized according to the Vitamin D Standardization
Program with the use of liquid chromatography-tandem mass spectrometry. Linear
and logistic regression models were used to assess the change in S-25(OH)D
concentrations.Results: Between 2000 and 2011, the mean S-25(OH)D increased from
48 nmol/L (95% CI: 47, 48 nmol/L) to 65 nmol/L (95% CI: 65, 66 nmol/L) (P <
0.001). The prevalence of vitamin D supplement users increased from 11% to 41% (P
< 0.001). When analyzing the effect of fortification of fluid milk products, we
focused on supplement nonusers. The mean increase in S-25(OH)D in daily fluid
milk consumers (n = 1017) among supplement nonusers was 20 nmol/L (95% CI: 19, 21
nmol/L), which was 6 nmol/L higher than nonconsumers (n = 229) (14 nmol/L; 95%
CI: 12, 16 nmol/L) (P < 0.001). In total, 91% of nonusers who consumed fluid milk
products, fat spreads, and fish based on Finnish nutrition recommendations
reached S-25(OH)D concentrations >50 nmol/L in 2011.Conclusions: The vitamin D
status of the Finnish adult population has improved considerably during the time
period studied. The increase is mainly explained by food fortification,
especially of fluid milk products, and augmented vitamin D supplement use. Other
factors, such as the difference in the ultraviolet radiation index between 2000
and 2011, may partly explain the results. When consuming vitamin D sources based
on the nutritional recommendations, vitamin D status is sufficient [S-25(OH)D
>=50 nmol/L], and supplementation is generally not needed.
PMID- 28490517
TI - ATOH1 Promotes Leptomeningeal Dissemination and Metastasis of Sonic Hedgehog
Subgroup Medulloblastomas.
AB - Medulloblastoma arising from the cerebellum is the most common pediatric brain
malignancy, with leptomeningeal metastases often present at diagnosis and
recurrence associated with poor clinical outcome. In this study, we used mouse
medulloblastoma models to explore the relationship of tumor pathophysiology and
dysregulated expression of the NOTCH pathway transcription factor ATOH1, which is
present in aggressive medulloblastoma subtypes driven by aberrant Sonic
Hedgehog/Patched (SHH/PTCH) signaling. In experiments with conditional ATOH1
mouse mutants crossed to Ptch1+/- mice, which develop SHH-driven medulloblastoma,
animals with Atoh1 transgene expression developed highly penetrant
medulloblastoma at a young age with extensive leptomeningeal disease and
metastasis to the spinal cord and brain, resembling xenografts of human SHH
medulloblastoma. Metastatic tumors retained abnormal SHH signaling like tumor
xenografts. Conversely, ATOH1 expression was detected consistently in recurrent
and metastatic SHH medulloblastoma. Chromatin immunoprecipitation sequencing and
gene expression profiling identified candidate ATOH1 targets in tumor cells
involved in development and tumorigenesis. Among these targets specific to
metastatic tumors, there was an enrichment in those implicated in extracellular
matrix remodeling activity, cytoskeletal network and interaction with
microenvironment, indicating a shift in transcriptomic and epigenomic landscapes
during metastasis. Treatment with bone morphogenetic protein or SHH pathway
inhibitors decreased tumor cell proliferation and suppressed metastatic tumor
growth, respectively. Our work reveals a dynamic ATOH1-driven molecular cascade
underlying medulloblastoma metastasis that offers possible therapeutic
opportunities. Cancer Res; 77(14); 3766-77. (c)2017 AACR.
PMID- 28490519
TI - Multiple factors influence population sex ratios in the Mojave Desert moss
Syntrichia caninervis.
AB - PREMISE OF RESEARCH: Natural populations of many mosses appear highly female
biased based on the presence of reproductive structures. This bias could be
caused by increased male mortality, lower male growth rate, or a higher threshold
for achieving sexual maturity in males. Here we test these hypotheses using
samples from two populations of the Mojave Desert moss Syntrichia caninervis.
METHODS: We used double-digest restriction-site associated DNA (RAD) sequencing
to identify candidate sex-associated loci in a panel of sex-expressing plants.
Next, we used putative sex-associated markers to identify the sex of individuals
without sex structures. KEY RESULTS: We found a 17:1 patch-level phenotypic
female to male sex ratio in the higher elevation site (Wrightwood) and no sex
expression at the low elevation site (Phelan). In contrast, on the basis of
genetic data, we found a 2:1 female bias at the Wrightwood site and only females
at the Phelan site. The relative area occupied by male and female genets was
indistinguishable, but males were less genetically diverse. CONCLUSIONS: Our data
suggest that both male-biased mortality and sexual dimorphism in thresholds for
sex expression could explain genetic and phenotypic sex ratio biases and that
phenotypic sex expression alone over-estimates the extent of actual sex ratio
bias present in these two populations of S. caninervis.
PMID- 28490518
TI - CHK1 Inhibition in Small-Cell Lung Cancer Produces Single-Agent Activity in
Biomarker-Defined Disease Subsets and Combination Activity with Cisplatin or
Olaparib.
AB - Effective targeted therapies for small-cell lung cancer (SCLC), the most
aggressive form of lung cancer, remain urgently needed. Here we report evidence
of preclinical efficacy evoked by targeting the overexpressed cell-cycle
checkpoint kinase CHK1 in SCLC. Our studies employed RNAi-mediated attenuation or
pharmacologic blockade with the novel second-generation CHK1 inhibitor
prexasertib (LY2606368), currently in clinical trials. In SCLC models in vitro
and in vivo, LY2606368 exhibited strong single-agent efficacy, augmented the
effects of cisplatin or the PARP inhibitor olaparib, and improved the response of
platinum-resistant models. Proteomic analysis identified CHK1 and MYC as top
predictive biomarkers of LY2606368 sensitivity, suggesting that CHK1 inhibition
may be especially effective in SCLC with MYC amplification or MYC protein
overexpression. Our findings provide a preclinical proof of concept supporting
the initiation of a clinical efficacy trial in patients with platinum-sensitive
or platinum-resistant relapsed SCLC. Cancer Res; 77(14); 3870-84. (c)2017 AACR.
PMID- 28490520
TI - Carbon allocation to growth and storage in two evergreen species of contrasting
successional status.
AB - PREMISE OF THE STUDY: A prevailing hypothesis in forest succession is that shade
tolerant species grow more slowly than shade-intolerant species, across light
conditions, because they prioritize carbon (C) allocation to storage. We examined
this hypothesis in a confamilial pair of species, including one of the fastest
growing tree species in the world (Eucalyptus globulus) and a shade-tolerant,
slow-growing species (Luma apiculata). METHODS: Seedlings were subjected to one
out of four combinations of light (high vs. low) and initial defoliation (90%
defoliated vs. nondefoliated) for four months. Growth, C storage concentration in
different organs, leaf shedding, and lateral shoot formation were measured at the
end of the experiment. KEY RESULTS: Eucalyptus globulus grew faster than L.
apiculata in high light, but not in low light. Both species had lower C storage
concentration in low than in high light, but similar C storage concentrations in
each light condition. Defoliation had no effect on C storage, except in the case
of the old leaves of both species, which showed lower C storage levels in
response to defoliation. Across treatments, leaf shedding was 96% higher in E.
globulus than in L. apiculata while, in contrast, lateral shoot formation was 87%
higher in L. apiculata. CONCLUSIONS: In low light, E. globulus prioritized C
storage instead of growth, whereas L. apiculata prioritized growth and lateral
branching. Our results suggest that shade tolerance depends on efficient light
capture rather than C conservation traits.
PMID- 28490521
TI - Survival in Women Versus Men Following Implantation of Pacemakers,
Defibrillators, and Cardiac Resynchronization Therapy Devices in a Large,
Nationwide Cohort.
AB - BACKGROUND: Whether outcomes differ between sexes following treatment with
pacemakers (PM), implantable cardioverter defibrillators, and cardiac
resynchronization therapy (CRT) devices is unclear. METHODS AND RESULTS:
Consecutive US patients with newly implanted PM, implantable cardioverter
defibrillators, and CRT devices from a large remote monitoring database between
2008 and 2011 were included in this observational cohort study. Sex-specific all
cause survival postimplant was compared within each device type using a
multivariable Cox proportional hazards model, stratified on age and adjusted for
remote monitoring utilization and ZIP-based socioeconomic variables. A total of
269 471 patients were assessed over a median 2.9 [interquartile range, 2.2, 3.6]
years. Unadjusted mortality rates (MR; deaths/100 000 patient-years) were similar
between women versus men receiving PMs (n=115 076, 55% male; MR 4193 versus MR
4256, respectively; adjusted hazard ratio, 0.87; 95% CI, 0.84-0.90; P<0.001) and
implantable cardioverter defibrillators (n=85 014, 74% male; MR 4417 versus MR
4479, respectively; adjusted hazard ratio, 0.98; 95% CI, 0.93-1.02; P=0.244). In
contrast, survival was superior in women receiving CRT defibrillators (n=61 475,
72% male; MR 5270 versus male MR 7175; adjusted hazard ratio, 0.73; 95% CI, 0.70
0.76; P<0.001) and also CRT pacemakers (n=7906, 57% male; MR 5383 versus male MR
7625, adjusted hazard ratio, 0.69; 95% CI, 0.61-0.78; P<0.001). This relative
difference increased with time. These results were unaffected by age or remote
monitoring utilization. CONCLUSIONS: Women accounted for less than 30% of high
voltage implants and fewer than half of low-voltage implants in a large, nation
wide cohort. Survival for women and men receiving implantable cardioverter
defibrillators and PMs was similar, but dramatically greater for women receiving
both defibrillator- and PM-based CRT.
PMID- 28490522
TI - Lifestyle and Risk of Screening-Detected Abdominal Aortic Aneurysm in Men.
AB - BACKGROUND: Modifiable lifestyle-related factors associated with risk of
abdominal aortic aneurysm (AAA) are rarely investigated with a prospective
design. We aimed to study possible associations among such factors and
comorbidities with mean abdominal aortic diameter (AAD) and with risk of AAA
among men screened for the disease. METHODS AND RESULTS: Self-reported lifestyle
related exposures were assessed at baseline (January 1, 1998) among 14 249 men
from the population-based Cohort of Swedish Men, screened for AAA between 65 and
75 years of age (mean 13 years after baseline). Multivariable prediction of mean
AAD was estimated with linear regression, and hazard ratios (HRs) of AAA (AAD
>=30 mm) with Cox proportional hazard regression. The AAA prevalence was 1.2%
(n=168). Smoking, body mass index, and cardiovascular disease were associated
with a larger mean AAD, whereas consumption of alcohol and diabetes mellitus were
associated with a smaller mean AAD. The HR of AAA was increased among
participants who were current smokers with >=25 pack-years smoked compared with
never smokers (HR 15.59, 95% CI 8.96-27.15), those with a body mass index >=25
versus <25 (HR 1.89, 95% CI, 1.22-2.93), and those with cardiovascular disease
(HR 1.77, 95% CI, 1.13-2.77), and hypercholesterolemia (HR 1.59, 95% CI 1.08
2.34). Walking or bicycling for >40 minutes/day (versus almost never) was
associated with lower AAA hazard (HR 0.59, 95% CI 0.36-0.97) compared with almost
never walking or bicycling. CONCLUSIONS: This prospective study confirms that
modifiable lifestyle-related factors are associated with AAD and with AAA
disease.
PMID- 28490523
TI - Race-Sex Differences in Statin Use and Low-Density Lipoprotein Cholesterol
Control Among People With Diabetes Mellitus in the Reasons for Geographic and
Racial Differences in Stroke Study.
AB - BACKGROUND: Statin therapy is a cornerstone of cardiovascular disease risk
reduction for people with diabetes mellitus. Past reports have shown race-sex
differences in statin use in general populations, but statin patterns by race and
sex in those with diabetes mellitus have not been thoroughly studied. METHODS AND
RESULTS: Our sample of 4288 adults >=45 years of age with diagnosed diabetes
mellitus who had low-density lipoprotein cholesterol (LDL-C) >100 mg/dL or were
taking statins recruited for the Reasons for Geographic and Racial Differences in
Stroke study from 2003 to 2007. Exposures included race-sex groups (white men
[WM], black men [BM], white women [WW], black women [BW]) and factors that may
influence healthcare utilization. Proportions and prevalence ratios were
calculated for statin use and LDL-C control. Statin use for WM, BM, WW, and BW
was 66.0%, 57.8%, 55.0%, and 53.6%, respectively (P<0.001). After adjustment for
healthcare utilization factors, statin use was lower for BM, WW, and BW compared
with WM (prevalence ratios [95%CI]: 0.96 [0.89-1.03], 0.86 [0.80-0.92], and 0.87
[0.81-0.93], respectively, P<0.001). LDL-C control among those taking statins for
WM, BM, WW, and BW was 75.3%, 62.7%, 69.0%, and 56.0%, respectively (P<0.001).
After adjustment, LDL-C control was lower for BM, WW, and BW compared with WM
(prevalence ratios [95%CI]: 0.85 [0.79-0.93], 0.89 [0.82-0.96], and 0.73 [0.67
0.80], respectively, P<0.001). CONCLUSIONS: Race-sex disparities in statin use
and LDL-C control were only partly explained by factors influencing health
services utilization. Healthcare provider awareness of these disparities may help
to close the observed race-sex gaps in statin use and LDL-C control among people
with diabetes mellitus.
PMID- 28490524
TI - Patients With Heart Failure Readmitted to the Original Hospital Have Better
Outcomes Than Those Readmitted Elsewhere.
AB - BACKGROUND: Up to one fifth of readmissions after a heart failure hospitalization
occur at a different hospital. This negatively impacts information continuity,
but whether site of readmission impacts subsequent outcomes is unclear. METHODS
AND RESULTS: Retrospective cohort study of all patients discharged with a primary
diagnosis of heart failure in Canada between April 2004 and December 2013. We
compared patients readmitted within 30 days to the original hospital versus a
different hospital. Of the 217 039 heart failure patients (mean age, 76.8 years,
50.1% male), 39 368 (18.1%) were readmitted within 30 days-32 771 (83.2%) to the
original hospital and 6597 (16.8%) to a different hospital (increasing over time
from 15.6% in 2004 to 18.5% by 2013; P for trend=0.001). Patients readmitted to
different hospitals were younger and were more likely to be male, have a rural
residence, a more-recent discharge year, an index hospitalization at a teaching
hospital, and to be brought in by ambulance at the time of the readmission.
Readmissions to the original hospital were substantially shorter (mean, 10.4 days
[95% CI, 10.3-10.6] versus 11.6 days [95% CI, 11.3-12.0]; adjusted means, 11.0
versus 12.0; P<0.0001) and had lower mortality (14.4% versus 15.0%; adjusted odds
ratio, 0.89; 95% CI, 0.82-0.96) than readmissions to different hospitals.
CONCLUSIONS: Readmissions to a different hospital are becoming more frequent over
time and are associated with longer stays and higher mortality rates than
readmissions to the original hospital. Our findings provide further evidence that
care fragmentation may be deleterious for patients with heart failure.
PMID- 28490525
TI - Five health issues that have dominated general elections.
PMID- 28490527
TI - Reversible plasticity of detrusor smooth muscle: evidence for a key role of
"slipping" actomyosin cross-bridges in the control of urinary bladder compliance.
PMID- 28490526
TI - ATP-citrate lyase is essential for high glucose-induced histone hyperacetylation
and fibrogenic gene upregulation in mesangial cells.
AB - The goal of this study was to address the role of ATP-citrate lyase (ACL), an
enzyme that converts citrate to acetyl-CoA, in high glucose (HG)-induced histone
acetylation and profibrotic gene expression. Our recent ChIP-Seq studies have
demonstrated that HG induces genome-wide histone hyperacetylation in mesangial
cells (MCs). Here, we showed that exposure of MCs to HG markedly increased
histone acetylation at the H3K9/14 and H3K18 marks and induced the expression of
potent profibrotic factors TGF-beta1, TGF-beta3, and connective tissue growth
factor (CTGF). The induction of these profibrotic factors was further enhanced by
histone deacetylase inhibitor but suppressed by histone acetyl-transferase
inhibitor, confirming the importance of histone acetylation in this regulation.
Interestingly, HG not only upregulated ACL expression but also promoted ACL
nuclear translocation, evidenced by increased ACL concentration and activity in
the nuclear extracts. Consistent with this observation, transfection of MCs with
a plasmid-carrying green fluorescent protein (GFP)-ACL fusion protein led to GFP
nuclear accumulation when cultured in HG condition. Silencing ACL with siRNAs
alleviated HG-induced histone hyperacetylation, as well as upregulation of TGF
beta1, TGF-beta3, CTGF, and extracellular matrix (ECM) proteins fibronectin and
collagen type IV, whereas ACL overexpression further enhanced HG induction of
histone acetylation, as well as these profibrotic factors and ECM proteins.
Collectively, these observations demonstrate that HG promotes ACL expression and
translocation into the nucleus, where ACL converts citrate to acetyl-CoA to
provide the substrate for histone acetylation, leading to upregulation of
fibrogenic genes. Therefore, ACL plays a critical role in epigenetic regulation
of diabetic renal fibrosis.
PMID- 28490529
TI - Effect of sodium nitrite on renal function and sodium and water excretion and
brachial and central blood pressure in healthy subjects: a dose-response study.
AB - Sodium nitrite (NaNO2) is converted to nitric oxide (NO) in vivo and has
vasodilatory and natriuretic effects. Our aim was to examine the effects of NaNO2
on hemodynamics, sodium excretion, and glomerular filtration rate (GFR). In a
single-blinded, placebo-controlled, crossover study, we infused placebo (0.9%
NaCl) or 0.58, 1.74, or 3.48 MUmol NaNO2.kg-1.h-1 for 2 h in 12 healthy subjects,
after 4 days of a standard diet. Subjects were supine and water loaded. We
measured brachial and central blood pressure (BP), plasma concentrations of
renin, angiotensin II, aldosterone, arginine vasopressin (P-AVP), and plasma
nitrite (P-[Formula: see text]), GFR by Cr-EDTA clearance, fractional excretion
of sodium (FENa) free water clearance (CH2O), and urinary excretion rate of
guanosine 3',5'-cyclic monophosphate (U-cGMP). The highest dose reduced brachial
systolic BP (5.6 mmHg, P = 0.003), central systolic BP (5.6 mmHg, P = 0.035), and
CH2O (maximum change from 3.79 to 1.27 ml/min, P = 0.031) and increased P
[Formula: see text] (from 0.065 to 0.766 MUmol/l, P < 0.001), while reducing U
cGMP (from 444 to 247 pmol/min, P = 0.004). GFR, FENa, P-AVP, and the components
in the renin-angiotensin-aldosterone system did not change significantly. In
conclusion, intravenous NaNO2 induced a dose-dependent reduction of brachial and
central BP. The hemodynamic effect was not mediated by the renin-angiotensin
aldosterone system. NaNO2 infusion resulted in a vasopressin-independent decrease
in CH2O and urine output but no change in urinary sodium excretion or GFR. The
lack of increase in cGMP accompanying the increase in [Formula: see text]
suggests a direct effect of nitrite or nitrate on the renal tubules and vascular
bed with little or no systemic conversion to NO.
PMID- 28490528
TI - Combining new tools to assess renal function and morphology: a holistic approach
to study the effects of aging and a congenital nephron deficit.
AB - Recently, new methods for assessing renal function in conscious mice
(transcutaneous assessment) and for counting and sizing all glomeruli in whole
kidneys (MRI) have been described. In the present study, these methods were used
to assess renal structure and function in aging mice, and in mice born with a
congenital low-nephron endowment. Age-related nephron loss was analyzed in adult
C57BL/6 mice (10-50 wk of age), and congenital nephron deficit was assessed in
glial cell line-derived neurotrophic factor heterozygous (GDNF HET)-null mutant
mice. Renal function was measured through the transcutaneous quantitation of
fluorescein isothiocyanate-sinistrin half-life (t1/2) in conscious mice. MRI was
used to image, count, and size cationic-ferritin labeled glomeruli in whole
kidneys ex vivo. Design-based stereology was used to validate the MRI
measurements of glomerular number and mean volume. In adult C57BL/6 mice, older
age was associated with fewer and larger glomeruli, and a rightward shift in the
glomerular size distribution. These changes coincided with a decrease in renal
function. GNDF HET mice had a congenital nephron deficit that was associated with
glomerular hypertrophy and exacerbated by aging. These findings suggest that
glomerular hypertrophy and hyperfiltration are compensatory processes that can
occur in conjunction with both age-related nephron loss and congenital nephron
deficiency. The combination of measurement of renal function in conscious animals
and quantitation of glomerular number, volume, and volume distribution provides a
powerful new tool for investigating aspects of renal aging and functional
changes.
PMID- 28490530
TI - IL-6 promotes epithelial-to-mesenchymal transition of human peritoneal
mesothelial cells possibly through the JAK2/STAT3 signaling pathway.
AB - Long-term peritoneal dialysis (PD) therapy results in functional and structural
alteration of the peritoneal membrane, including epithelial-to-mesenchymal
transition (EMT). Interleukin 6 (IL-6) is a local pleiotropic cytokine,
hypothesized to play an important role in EMT. This study was designed to
investigate the role of IL-6 in EMT and peritoneal membrane dysfunction in long
term PD patients by assessing the level of IL-6 in dialysate and exploring the
relationship between IL-6, the related signaling pathway JAK2/STAT3, and EMT,
using in vitro cellular and molecular techniques. Plasma and dialysate levels of
IL-6 were significantly higher in PD ultrafiltration failure patients compared
with patients without ultrafiltration failure and were negatively correlated with
measures of PD adequacy. In vitro IL-6 treatment changed human peritoneal
mesothelial cell phenotype from a typical cobblestone-like to a fibroblast-like
appearance and increased cell viability. IL-6 treatment increased alpha-smooth
muscle actin and vascular endothelial growth factor expression but decreased E
cadherin expression. IL-6 treatment activated the JAK/STAT signaling pathway.
However, the JAK2/STAT3 inhibitor WP1066 prevented IL-6-induced activation of the
JAK2/STAT3 pathway and EMT. We conclude that IL-6 promotes the EMT process,
possibly by activating the JAK2/STAT3 signaling pathway. IL-6 may serve as a
novel therapeutic target for preventing EMT, and preservation of the peritoneal
membrane may arise from these studies.
PMID- 28490531
TI - The effects of angiotensin-(1-7) on the exchanger NHE3 and on [Ca2+]i in the
proximal tubules of spontaneously hypertensive rats.
AB - The acute effects of angiotensin-1-7 [ANG-(1-7)] on the reabsorptive bicarbonate
flow (J[Formula: see text]) were evaluated using stationary microperfusion in
vivo in the proximal tubules of spontaneously hypertensive rats (SHR) and their
normotensive controls, Wistar-Kyoto (WKY) rats, using a microelectrode sensitive
to H+ In WKY rats, the control J[Formula: see text] was 2.40 +/- 0.10 nmol.cm-2.s
1 (n = 120); losartan (10-7 M) or A779 (10-6 M, a specific Mas antagonist), alone
or in combination with losartan, decreased the J[Formula: see text] ANG-(1-7) had
biphasic effects on J[Formula: see text]: at 10-9 M, it inhibited, and at 10-6,
it stimulated the flow. S3226 [10-6 M, a specific Na+-H+ exchanger 3 (NHE3)
antagonist] decreased J[Formula: see text] and changed the stimulatory effect of
ANG-(1-7) to an inhibitory one but did not alter the inhibitory action of ANG-(1
7). In SHR, the control J[Formula: see text] was 2.04 +/- 0.13 nmol.cm-2.s-1 (n =
56), and A779 and/or losartan reduced the flow. ANG-(1-7) at 10-9 M increased
J[Formula: see text], and ANG-(1-7) at 10-6 M reduced it. The effects of A779,
losartan, and S3226 on the J[Formula: see text] were similar to those found in
WKY rats, which indicated that in SHR, the ANG-(1-7) action on the NHE3 was via
Mas and ANG II type 1. The cytosolic calcium in the WKY or SHR rats was ~100 nM
and was increased by ANG-(1-7) at 10-9 or 10-6 M. In hypertensive animals, a high
plasma level of ANG-(1-7) inhibited NHE3 in the proximal tubule, which mitigated
the hypertension caused by the high plasma level of ANG II.
PMID- 28490534
TI - Malaria Transmission and Prospects for Malaria Eradication: The Role of the
Environment.
AB - Environmental factors affect the transmission intensity, seasonality, and
geographical distribution of malaria, and together with the vector, the human,
and the parasite compose the malaria system. Strategies that alter the
environment are among the oldest interventions for malaria control, but currently
are not the most prominent despite historical evidence of their effectiveness.
The importance of environmental factors, the role they play considering the
current goals of malaria eradication, the different strategies that can be
adopted, and the current challenges for their implementation are discussed. As
malaria elimination/eradication takes a prominent place in the health agenda, an
integrated action, addressing all elements of the malaria system, which
contributes to improved knowledge and to building local capacity and that brings
about positive effects to the health of the local population has the greatest
chance to produce fast, effective, and sustainable results.
PMID- 28490533
TI - The tryptophan/kynurenine pathway, systemic inflammation, and long-term outcome
after kidney transplantation.
AB - Tryptophan is metabolized along the kynurenine pathway, initially to kynurenine,
and subsequently to cytotoxic 3-hydroxykynurenine. There is increasing interest
in this pathway because of its proinflammatory nature, and drugs interfering in
it have received increasing attention. We aimed to investigate whether serum and
urinary parameters of the tryptophan/kynurenine pathway, and particularly
cytotoxic 3-hydroxykynurenine, are associated with systemic inflammation and long
term outcome in renal transplant recipients (RTR). Data were collected in
outpatient RTR with a functioning graft for >1 yr. Tryptophan, kynurenine, and 3
hydroxykynurenine in serum and urine were measured using LC-MS/MS. A total of 561
RTR (age: 51 +/- 12 yr; 56% male) were included at a median of 6.0 (2.6-11.6) yr
posttransplantation. Baseline median serum tryptophan was 40.0 (34.5-46.0)
umol/l, serum kynurenine was 1.8 (1.4-2.2) umol/l, and serum 3-hydroxykynurenine
was 42.2 (31.0-61.7) nmol/l. Serum kynurenine and 3-hydroxykynurenine were
strongly associated with parameters of systemic inflammation. During follow-up
for 7.0 (6.2-7.5) yr, 51 RTR (9%) developed graft failure and 120 RTR (21%) died.
Both serum kynurenine and 3-hydroxykynurenine were independently associated with
graft failure [HR 1.72 (1.23-2.41), P = 0.002; and HR 2.03 (1.42-2.90), P <
0.001]. Serum 3-hydroxykynurenine was also independently associated with
mortality [HR 1.37 (1.08-1.73), P = 0.01], whereas serum kynurenine was not.
Urinary tryptophan/kynurenine pathway parameters were not associated with
outcome. Of tryptophan metabolites, serum 3-hydroxykynurenine is cross
sectionally most strongly and consistently associated with systemic inflammation
and prospectively with adverse long-term outcome after kidney transplantation.
Serum 3-hydroxykynurenine may be an interesting biomarker and target for the
evaluation of drugs interfering in the tryptophan/kynurenine pathway.
PMID- 28490532
TI - Podocyte-specific knockout of cyclooxygenase 2 exacerbates diabetic kidney
disease.
AB - Enhanced expression of cyclooxygenase 2 (COX2) in podocytes contributes to
glomerular injury in diabetic kidney disease, but some basal level of podocyte
COX2 expression might be required to promote podocyte attachment and/or survival.
To investigate the role of podocyte COX2 expression in diabetic kidney disease,
we deleted COX2 specifically in podocytes in a mouse model of Type 1 diabetes
mellitus (Akita mice). Podocyte-specific knockout (KO) of COX2 did not affect
renal morphology or albuminuria in nondiabetic mice. Albuminuria was
significantly increased in wild-type (WT) and KO Akita mice compared with
nondiabetic controls, and the increase in albuminuria was significantly greater
in KO Akita mice compared with WT Akita mice at both 16 and 20 wk of age. At the
20-wk time point, mesangial expansion was also increased in WT and KO Akita mice
compared with nondiabetic animals, and these histologic abnormalities were not
improved by KO of COX2. Tubular injury was seen only in diabetic mice, but there
were no significant differences between groups. Thus, KO of COX2 enhanced
albuminuria and did not improve the histopathologic features of diabetic kidney
disease. These data suggest that 1) KO of COX2 in podocytes does not ameliorate
diabetic kidney disease in Akita mice, and 2) some basal level of podocyte COX2
expression in podocytes is necessary to attenuate the adverse effects of diabetes
on glomerular filtration barrier function.
PMID- 28490535
TI - Vaccines to Accelerate Malaria Elimination and Eventual Eradication.
AB - Remarkable progress has been made in coordinated malaria control efforts with
substantial reductions in malaria-associated deaths and morbidity achieved
through mass administration of drugs and vector control measures including
distribution of long-lasting insecticide-impregnated bednets and indoor residual
spraying. However, emerging resistance poses a significant threat to the
sustainability of these interventions. In this light, the malaria research
community has been charged with the development of a highly efficacious vaccine
to complement existing malaria elimination measures. As the past 40 years of
investment in this goal attests, this is no small feat. The malaria parasite is a
highly complex organism, exquisitely adapted for survival under hostile
conditions within human and mosquito hosts. Here we review current vaccine
strategies to accelerate elimination and the potential for novel and innovative
approaches to vaccine design through a better understanding of the host-parasite
interaction.
PMID- 28490536
TI - The Bioenergetics of Exercise.
AB - Animals possess a remarkable ability to perform physical activity over a wide
range of workloads and durations, reflecting both the inherent efficiency and
large reserve capacity of energy transfer systems. Deciphering how different
organ/physiological systems respond to the acute and chronic demands of exercise
depends on a foundational understanding of the redox and bioenergetic principles
that underlie the flow of electrons in living systems and its coupling to ATP
synthesis. The purpose of this review is to set the stage to cover (1) the
thermodynamic driving forces responsible for generating and maintaining the
energy charge that establishes and sustains life for cells, and (2) how cellular
energy transfer systems respond to changes in energy demand to ensure energy
charge is preserved.
PMID- 28490537
TI - Adaptations to Endurance and Strength Training.
AB - The capacity for human exercise performance can be enhanced with prolonged
exercise training, whether it is endurance- or strength-based. The ability to
adapt through exercise training allows individuals to perform at the height of
their sporting event and/or maintain peak physical condition throughout the life
span. Our continued drive to understand how to prescribe exercise to maximize
health and/or performance outcomes means that our knowledge of the adaptations
that occur as a result of exercise continues to evolve. This review will focus on
current and new insights into endurance and strength-training adaptations and
will highlight important questions that remain as far as how we adapt to
training.
PMID- 28490539
TI - Physiological Redundancy and the Integrative Responses to Exercise.
AB - The biological responses to acute and chronic exercise are marked by a high level
of physiological redundancy that operates at various levels of integration,
including the molecular, cellular, organ-system, and whole-body scale. During
acute exercise, this redundancy protects whole-body homeostasis in the face of 10
fold or more increases in whole-body metabolic rate. In some cases, there are
"trade-offs" between optimizing the performance of a given organ or system versus
whole-body performance. Physiological redundancy also plays a key role in the
adaptive responses to exercise training and high levels of habitual physical
activity, including the positive effects of regular exercise on health.
Appreciation of the general principles of physiological redundancy is critical to
(1) gain an overall understanding of short- and long-term responses to exercise,
and (2) place physiological responses occurring at various levels of integration
in perspective.
PMID- 28490540
TI - The Biology of Plasmodium vivax.
AB - Plasmodium vivax is the second most prevalent cause of malaria worldwide and the
leading cause of malaria outside of Africa. Although infections are seldom fatal
clinical disease can be debilitating and imposes significant health and economic
impacts on affected populations. Estimates of transmission and prevalence
intensity can be problematic because many episodes of vivax originate from
hypnozoite stages in the liver that have remained dormant from previous
infections by an unknown mechanism. Lack of treatment options to clear
hypnozoites and the ability to infect mosquitoes before disease symptoms present
represent major challenges for control and eradication of vivax malaria.
Compounding these challenges is the unique biology of P. vivax and limited
progress in development of experimental research tools, thereby hindering
development of new drugs and vaccines. Renewed emphasis on vivax malaria research
is beginning to make progress in overcoming some of these challenges.
PMID- 28490538
TI - Cellular Constituents of the Prostate Stroma: Key Contributors to Prostate Cancer
Progression and Therapy Resistance.
AB - Reciprocal signaling between prostate stroma and its epithelium are fundamental
to organ development and homeostasis. Similarly, interactions between tumor cells
and stromal constituents are central to key aspects of carcinogenesis and
malignancy growth involving tumor cell invasion, dissemination, and growth in
distant sites. The prostate stroma is complex with several distinct resident cell
types, infiltrating nonresident cell types and an amalgam of structural matrix
factors, matricellular proteins, metabolites, growth factors, and cytokines. Of
importance, the stroma is dynamic with changes in composition as a cause or
consequence of intrinsic and extrinsic factors. In the context of epithelial
neoplasia, the prostate stroma undergoes phenotypic changes with a loss of well
differentiated smooth muscle cell population and the expansion of cancer
associated fibroblast populations. This reactive stroma further coevolves with
tumor progression. Recent studies show the role of tumor microenvironment
components in therapy resistance and highlight the importance of a thorough
knowledge of cross talk between tumor cells and microenvironment niches to
develop new therapeutic strategies.
PMID- 28490541
TI - Exosomes as Mediators of the Systemic Adaptations to Endurance Exercise.
AB - Habitual endurance exercise training is associated with multisystemic metabolic
adaptations that lower the risk of inactivity-associated disorders such as
obesity and type 2 diabetes mellitus (T2DM). Identification of complex systemic
signaling networks responsible for these benefits are of great interest because
of their therapeutic potential in metabolic diseases; however, specific signals
that modulate the multisystemic benefits of exercise in multiple tissues and
organs are only recently being discovered. Accumulated evidence suggests that
muscle and other tissues have an endocrine function and release peptides and
nucleic acids into the circulation in response to acute endurance exercise to
mediate the multisystemic adaptations. Factors released from skeletal muscle have
been termed myokines and we propose that the total of all factors released in
response to endurance exercise (including peptides, nucleic acids, and
metabolites) be termed, "exerkines." We propose that many of the exerkines are
released within extracellular vesicles called exosomes, which regulate peripheral
organ cross talk. Exosomes (30-140 nm) and larger microvesicles [MVs] (100-1000
nm) are subcategories of extracellular vesicles that are released into the
circulation. Exosomes contain peptides and several nucleic acids (microRNA
[miRNA], messenger RNA [mRNA], mitochondrial DNA [mtDNA]) and are involved in
intercellular/tissue exchange of their contents. An acute bout of endurance
exercise increases circulating exosomes that are hypothesized to mediate organ
cross talk to promote systemic adaptation to endurance exercise. Further support
for the role of exosomes (and possibly MVs) in mediating the systemic benefits of
exercise comes from the fact that the majority of the previously reported
myokines/exerkines are found in extracellular vesicles databases (Vesiclepedia
and ExoCarta). We propose that exosomes isolated from athletes following exercise
or exosomes bioengineered to incorporate one or many of known exerkines will be
therapeutically useful in the treatment of obesity, T2DM, and other aging
associated metabolic disorders.
PMID- 28490542
TI - Evolution of Premalignant Disease.
AB - Where does cancer come from? Although the cell-of-origin is difficult to
pinpoint, cancer clones harbor information about their clonal ancestries. In an
effort to find cells before they evolve into a life-threatening cancer,
physicians currently diagnose premalignant diseases at frequencies that
substantially exceed those of clinical cancers. Cancer risk prediction relies on
our ability to distinguish between which premalignant features will lead to
cancer mortality and which are characteristic of inconsequential disease. Here,
we review the evolution of cancer from premalignant disease, and discuss the
concept that even phenotypically normal cell progenies inherently gain more
malignant potential with age. We describe the hurdles of prognosticating cancer
risk in premalignant disease by making reference to the underlying continuous and
multivariate natures of genotypes and phenotypes and the particular challenge
inherent in defining a cell lineage as "cancerized."
PMID- 28490544
TI - Does India really not have enough money to spend on healthcare?
PMID- 28490543
TI - Molecular Regulation of Exercise-Induced Muscle Fiber Hypertrophy.
AB - Skeletal muscle hypertrophy is a widely sought exercise adaptation to counteract
the muscle atrophy of aging and disease, or to improve athletic performance.
While this desired muscle enlargement is a well-known adaptation to resistance
exercise training (RT), the mechanistic underpinnings are not fully understood.
The purpose of this review is thus to provide the reader with a summary of recent
advances in molecular mechanisms-based on the most current literature-that are
thought to promote RT-induced muscle hypertrophy. We have therefore focused this
discussion on the following areas of fertile investigation: ribosomal function
and biogenesis, muscle stem (satellite) cell activity, transcriptional
regulation, mechanotransduction, and myokine signaling.
PMID- 28490545
TI - Red blood cell distribution width and myocardial scar burden in coronary artery
disease.
AB - INTRODUCTION: Red blood cell distribution width (RDW) is a novel independent
marker of cardiovascular disease including heart failure, coronary artery disease
and myocardial ischaemia. The aim of the study was to investigate a possible
relationship between RDW and myocardial scar burden, as assessed by a MIBI
viability scan. A secondary objective was to assess whether there is an
association between RDW and left ventricular ejection fraction (LVEF). METHODS:
The study comprised 123 subjects with ischaemic heart disease who underwent a
myocardial viability scan between June 2008 and July 2014. Haemoglobin, mean
corpuscular volume, RDW, platelet count, mean platelet volume (MPV), estimated
glomerular filtration rate, fasting blood glucose, liver and lipid profiles were
evaluated for all patients. The extent of myocardial scarring and LVEF were
noted. Data were analysed using IBM SPSS Statistics 22.0. Univariate followed by
multivariate analyses were performed to assess for independent predictors of
myocardial scarring and LVEF, respectively. RESULTS: The mean age of the study
population was 63.5 years; most of the subjects were men. The median LVEF was 31%
and median percentage of myocardial scarring was 8.7%. Multivariate analyses
revealed that RDW, HDL-cholesterol and alanine transaminase were independent
predictors of myocardial scarring while RDW, MPV, LDL-cholesterol and gamma
glutamyl transpeptidase were independent predictors of LVEF. CONCLUSIONS:
Increased RDW is an independent predictor both of myocardial scar burden and of
impaired left ventricular function in subjects with coronary artery disease.
PMID- 28490546
TI - A multicentre evaluation of an opioid patient-provider agreement.
AB - The role of the patient-provider agreement (PPA) is to set forth respective roles
and responsibilities for opioid therapy with the goal of improving outcomes,
reducing risks, and improving patient education. The Food and Drug Administration
(FDA) Safe Use Initiative Opioid PPA Working Group convened to develop a PPA and
test it for acceptability as an educational and shared decision-making tool in
opioid therapy. This multicentre study evaluated the utility of the PPA, how
readily patients understood it, its ability to educate patients in an unbiased
way about opioid treatment and the feasibility of incorporating a PPA in clinical
practice. A total of 117 patients and 14 providers at urban centres were included
(mean patient age: 56 years) with 85% of patients treated for pain for >3 months.
Most patients reported the PPA to be 'somewhat helpful' or 'very helpful' in
deciding a course of treatment (96%) and 'easy to understand' (97%). Both
patients and prescribers (89% and 92%, respectively) found the PPA was neutral in
terms of presenting opioid therapy. Most centres found the PPA could be
administered in <=10 min and 72% of prescribers said this PPA could be readily
incorporated into their practice. This PPA was perceived by both patients and
prescribers as helpful in deciding a course of treatment and unbiased in terms of
presentation of the risks and benefits of opioid therapy.
PMID- 28490547
TI - Board certification in Japan: corruption and near-collapse of reform.
PMID- 28490549
TI - Possible relationship between general and pregnancy-related anxiety during the
first half of pregnancy and the birth process: a prospective cohort study.
AB - OBJECTIVES: The rate of interventions during childbirth has increased
dramatically during the last decades. Maternal anxiety might play a role in the
progress of the labour process and interventions during labour. This study aimed
to identify associations between anxiety in the first half of pregnancy and the
birth process, including any interventions required during labour. In addition,
differences in the associations by parity and ethnicity were explored. DESIGN:
Prospective cohort study. SETTING: Primary care midwifery practices and
secondary/tertiary care obstetric practices in Amsterdam, participating in the
multiethnic ABCD (Amsterdam Born Children and their Development) study
(participation rate 96%; response 8266/12 373 (67%)). PARTICIPANTS: Included were
women with singletons, alive at labour start, with a gestational age >=24 weeks
(n=6443). INDEPENDENT VARIABLE: General anxiety (State-Trait Anxiety Inventory
state) and pregnancy-related anxiety (Pregnancy-Related Anxieties Questionnaire
(PRAQ)) were self-reported in the first half of pregnancy. OUTCOMES: Associations
between both forms of anxiety and several indicators of the birth process were
analysed. Subgroup analyses were performed for parity and ethnicity. RESULTS: The
prevalence of high general anxiety (State-Trait Anxiety Inventory score >=43) and
pregnancy-related anxiety (PRAQ score >=P90) were 30.9% and 11.0%, respectively.
After adjustment, in nulliparae, both general anxiety and pregnancy-related
anxiety were associated with pain relief and/or sedation (OR for general anxiety
1.23; 95% CI 1.02 to 1.48; OR for pregnancy-related anxiety 1.45; 95% CI 1.14 to
1.85). In multiparae, general anxiety was associated with induction of labour (OR
1.53; 95% CI 1.16 to 2.03) and pregnancy-related anxiety was associated with
primary caesarean section (OR 1.66; 95% CI 1.02 to 2.70). Associations were
largely similar for all ethnicities. CONCLUSIONS: High levels of general and
pregnancy-related anxiety in early pregnancy contribute modestly to more
interventions during the birth process with similar associations between ethnic
groups, but with some differences between nulliparae and multiparae.
PMID- 28490550
TI - Multimorbidity as an important issue among women: results of a gender difference
investigation in a large population-based cross-sectional study in West Asia.
AB - OBJECTIVES: To investigate the impact of gender on multimorbidity in northern
Iran. DESIGN: A cross-sectional analysis of the Golestan cohort data. SETTING:
Golestan Province, Iran. STUDY POPULATION: 49 946 residents (age 40-75 years) of
Golestan Province, Iran. MAIN OUTCOME MEASURES: Researchers collected data
related to multimorbidity, defined as co-existence of two or more chronic
diseases in an individual, at the beginning of a representative cohort study
which recruited its participants from 2004 to 2008. The researchers utilised
simple and multiple Poisson regression models with robust variances to examine
the simultaneous effects of multiple factors. RESULTS: Women had a 25.0%
prevalence of multimorbidity, whereas men had a 13.4% prevalence (p<0.001). Women
of all age-groups had a higher prevalence of multimorbidity. Of note,
multimorbidity began at a lower age (40-49 years) in women (17.3%) compared with
men (8.6%) of the same age (p<0.001). This study identified significant
interactions between gender as well as socioeconomic status, ethnicity, physical
activity, marital status, education level and smoking (p<0.01). CONCLUSION:
Prevention and control of multimorbidity requires health promotion programmes to
increase public awareness about the modifiable risk factors, particularly among
women.
PMID- 28490551
TI - Selective impact of disease on short-term and long-term components of self
reported memory: a population-based HUNT study.
AB - BACKGROUND: Subjective memory is commonly considered to be a unidimensional
measure. However, theories of performance-based memory suggest that subjective
memory could be divided into more than one dimension. OBJECTIVE: To divide
subjective memory into theoretically related components of memory and explore the
relationship to disease. METHODS: In this study, various aspects of self-reported
memory were studied with respect to demographics and diseases in the third wave
of the HUNT epidemiological study in middle Norway. The study included all
individuals 55 years of age or older, who responded to a nine-item questionnaire
on subjective memory and questionnaires on health (n=18 633). RESULTS: A
principle component analysis of the memory items resulted in two memory
components; the criterion used was an eigenvalue above 1, which accounted for 54%
of the total variance. The components were interpreted as long-term memory (LTM;
the first component; 43% of the total variance) and short-term memory (STM; the
second component; 11% of the total variance). Memory impairment was significantly
related to all diseases (except Bechterew's disease), most strongly to brain
infarction, heart failure, diabetes, cancer, chronic obstructive pulmonary
disease and whiplash. For most diseases, the STM component was more affected than
the LTM component; however, in cancer, the opposite pattern was seen.
CONCLUSIONS: Subjective memory impairment as measured in HUNT contained two
components, which were differentially associated with diseases.
PMID- 28490552
TI - Coffee, including caffeinated and decaffeinated coffee, and the risk of
hepatocellular carcinoma: a systematic review and dose-response meta-analysis.
AB - OBJECTIVES: To examine the association between coffee, including caffeinated and
decaffeinated coffee, with hepatocellular carcinoma (HCC) and assess the
influence of HCC aetiology and pre-existing liver disease. DESIGN: We performed a
systematic review and meta-analysis. We calculated relative risks (RRs) of HCC
according to caffeinated and decaffeinated coffee consumption using a random
effects dose-response meta-analysis. We tested for modification of the effect
estimate by HCC aetiology and pre-existing liver disease. We judged the quality
of evidence using the Grading of Recommendations Assessment, Development and
Evaluation (GRADE) criteria. RESULTS: We found 18 cohorts, involving 2 272 642
participants and 2905 cases, and 8 case-control studies, involving 1825 cases and
4652 controls. An extra two cups per day of coffee was associated with a 35%
reduction in the risk of HCC (RR 0.65, 95% CI 0.59 to 0.72). The inverse
association was weaker for cohorts (RR 0.71, 95% CI 0.65 to 0.77), which were
generally of higher quality than case-control studies (RR 0.53, 95% CI 0.41 to
0.69). There was evidence that the association was not significantly altered by
stage of liver disease or the presence/absence of high alcohol consumption, high
body mass index, type 2 diabetes mellitus, smoking, or hepatitis B and C viruses.
An extra two cups of caffeinated and decaffeinated coffee (2 and 3 cohort
studies, respectively) were associated with reductions of 27% (RR 0.73, 95% CI
0.63 to 0.85) and 14% (RR 0.86, 95% CI 0.74 to 1.00) in the risk of HCC. However,
due to a lack of randomised controlled trials, potential publication bias and
there being no accepted definition of coffee, the quality of evidence under the
GRADE criteria was 'very low'. CONCLUSIONS: Increased consumption of caffeinated
coffee and, to a lesser extent, decaffeinated coffee are associated with reduced
risk of HCC, including in pre-existing liver disease. These findings are
important given the increasing incidence of HCC globally and its poor prognosis.
PMID- 28490553
TI - Using a patient decision aid for insulin initiation in patients with type 2
diabetes: a qualitative analysis of doctor-patient conversations in primary care
consultations in Malaysia.
AB - OBJECTIVE: To investigate whether the use of apatient decision aid (PDA) for
insulin initiation fulfils its purpose of facilitating patient-centred decision
making through identifying how doctors and patients interact when using the PDA
during primary care consultations. DESIGN: Conversation analysis of seven single
cases of audio-recorded/video-recorded consultations between doctors and patients
with type 2 diabetes, using a PDA on starting insulin. SETTING: Primary care in
three healthcare settings: (1) one private clinic; (2) two public community
clinics and (3) one primary care clinic in a public university hospital, in
Negeri Sembilan and the Klang Valley in Malaysia. PARTICIPANTS: Clinicians and
seven patients with type 2 diabetes to whom insulin had been recommended.
Purposive sampling was used to select a sample high in variance across healthcare
settings, participant demographics and perspectives on insulin. PRIMARY OUTCOME
MEASURES: Interaction between doctors and patients in a clinical consultation
involving the use of a PDA about starting insulin. RESULTS: Doctors brought the
PDA into the conversation mainly by asking information-focused 'yes/no'
questions, and used the PDA for information exchange only if patients said they
had not read it. While their contributions were limited by doctors' questions,
some patients disclosed issues or concerns. Although doctors' PDA-related
questions acted as a presequence to deliberation on starting insulin, their
interactional practices raised questions on whether patients were informed and
their preferences prioritised. CONCLUSIONS: Interactional practices can hinder
effective PDA implementation, with habits from ordinary conversation potentially
influencing doctors' practices and complicating their implementation of patient
centred decision-making. Effective interaction should therefore be emphasised in
the design and delivery of PDAs and in training clinicians to use them.
PMID- 28490554
TI - Feasibility cluster randomised controlled trial of a within-consultation
intervention to reduce antibiotic prescribing for children presenting to primary
care with acute respiratory tract infection and cough.
AB - OBJECTIVE: To investigate recruitment and retention, data collection methods and
the acceptability of a 'within-consultation' complex intervention designed to
reduce antibiotic prescribing. DESIGN: Primary care feasibility cluster
randomised controlled trial. SETTING: 32 general practices in South West England
recruiting children from October 2014 to April 2015. PARTICIPANTS: Children (aged
3 months to <12 years) with acute cough and respiratory tract infection (RTI).
INTERVENTION: A web-based clinician-focussed clinical rule to predict risk of
future hospitalisation and a printed leaflet with individualised child health
information for carers, safety-netting advice and a treatment decision record.
CONTROLS: Usual practice, with clinicians recording data on symptoms, signs and
treatment decisions. RESULTS: Of 542 children invited, 501 (92.4%) consented to
participate, a month ahead of schedule. Antibiotic prescribing data were
collected for all children, follow-up data for 495 (98.8%) and the National
Health Service resource use data for 494 (98.6%). The overall antibiotic
prescribing rates for children's RTIs were 25% and 15.8% (p=0.018) in
intervention and control groups, respectively. We found evidence of
postrandomisation differential recruitment: the number of children recruited to
the intervention arm was higher (292 vs 209); over half were recruited by
prescribing nurses compared with less than a third in the control arm; children
in the intervention arm were younger (median age 2 vs 3 years controls, p=0.03)
and appeared to be more unwell than those in the control arm with higher
respiratory rates (p<0.0001), wheeze prevalence (p=0.007) and global illness
severity scores assessed by carers (p=0.045) and clinicians (p=0.01). Interviews
with clinicians confirmed preferential recruitment of less unwell children to the
trial, more so in the control arm. CONCLUSION: Differential recruitment may
explain the paradoxical antibiotic prescribing rates. Future cluster level
studies should consider designs which remove the need for individual consent
postrandomisation and embed the intervention within electronic primary care
records. TRIAL REGISTRATION NUMBER: ISRCTN 23547970 UKCRN STUDY ID: 16891.
PMID- 28490555
TI - Telehealthcare for patients suffering from chronic obstructive pulmonary disease:
effects on health-related quality of life: results from the Danish 'TeleCare
North' cluster-randomised trial.
AB - OBJECTIVE: To assess the effect of telehealthcare compared with usual practice in
patients with chronic obstructive pulmonary disease (COPD). DESIGN: A cluster
randomised trial with 26 municipal districts that were randomly assigned either
to an intervention group whose members received telehealthcare in addition to
usual practice or to a control group whose members received usual practice only
(13 districts in each arm). SETTING: Twenty-six municipal districts in the North
Denmark Region of Denmark. PARTICIPANTS: Patients who fulfilled the Global
Initiative for COPD guidelines and one of the following criteria: COPD Assessment
Test score >=10; or Medical Research Dyspnoea Council Scale >=3; or Modified
Medical Research Dyspnoea Council Scale >=2; or >=2 exacerbations during the past
12 months. MAIN OUTCOME MEASURES: Health-related quality of life (HRQoL) assessed
by the physical component summary (PCS) and mental component summary (MCS) scores
of the Short Form 36-Item Health Survey, Version 2. Data were collected at
baseline and at 12 month follow-up and analysed according to the intention-to
treat principle with complete cases, n=574 (258 interventions; 316 controls) and
imputed data, n=1225 (578 interventions, 647 controls) using multilevel
modelling. RESULTS: In the intention-to-treat analysis (n=1225), the raw mean
difference in PCS from baseline to 12 month follow-up was -2.6 (SD 12.4) in the
telehealthcare group and -2.8 (SD 11.9) in the usual practice group. The raw mean
difference in MCS scores in the same period was -4.7 (SD 16.5) and -5.3 (SD 15.5)
for telehealthcare and usual practice, respectively. The adjusted mean difference
in PCS and MCS between groups at 12 months was 0.1 (95% CI -1.4 to 1.7) and 0.4
(95% CI -1.7 to 2.4), respectively. CONCLUSIONS: The overall sample and all
subgroups demonstrated no statistically significant differences in HRQoL between
telehealthcare and usual practice. TRIAL REGISTRATION NUMBER: NCT01984840;
Results.
PMID- 28490556
TI - Maternal alcohol disorders and school achievement: a population cohort record
linkage study in Western Australia.
AB - OBJECTIVE: Maternal alcohol use disorder is a risk factor for a range of
developmental outcomes in children. This study examines school achievement in
children of Indigenous and non-Indigenous mothers with an alcohol-related
diagnosis. DESIGN, SETTING AND PARTICIPANTS: This is a Western Australian
population cohort study of mothers with a record of an alcohol-related diagnosis
classified by the International Classification of Diseases Revisions 9/10 codes
as recorded on administrative databases, and of their offspring born between 1989
and 2007 (n=18 486 exposed children), with a frequency matched comparison cohort
of mothers with no record of alcohol diagnosis and their offspring (n=48 262
comparison children). OUTCOMES: Records were linked with school achievement data
for numeracy and literacy from Years 3, 5, 7 and 9 (age range: ~8-14 years) based
on statewide and national testing. Mixed multivariate models with a random
intercept per child were used to assess the relationship between exposure and the
timing of exposure with failure to meet minimum standardised benchmarks. RESULTS:
Academic achievement was lower in all testing domains (reading, writing, spelling
and numeracy) among children of mothers with an alcohol diagnosis and persisted
across all year groups examined. The highest ORs at Year 9 for non-Indigenous
children were in reading (adjusted OR (aOR) 1.6, 95% CI 1.4 to 1.8) and in
writing for Indigenous children (aOR 2.0, 95% CI 1.8 to 2.3). CONCLUSION:
Children of mothers with alcohol use disorders are at risk of not meeting minimum
educational benchmarks in numeracy and literacy, with the risk highest among
Indigenous children.
PMID- 28490557
TI - The effect of empagliflozin on oxidative nucleic acid modifications in patients
with type 2 diabetes: protocol for a randomised, double-blinded, placebo
controlled trial.
AB - INTRODUCTION: Cardiovascular disease is the leading cause of morbidity and
mortality in patients with type 2 diabetes (T2D). Although glycaemic control
reduces microvascular complications, the effect of intensive treatment strategies
or individual drugs on macrovascular diseases is still debated. RNA oxidation is
associated with increased mortality in patients with T2D. Inspired by animal
studies showing effect of a sodium-glucose cotransporter-2 (SGLT-2) inhibitor
(empagliflozin) on oxidative stress and a recent trial evaluating empagliflozin
that demonstrated improved cardiovascular outcomes in patients with T2D at high
risk of cardiovascular events, we hypothesise that empagliflozin lowers oxidative
stress. METHODS AND ANALYSIS: In this randomised, double-blinded and placebo
controlled study, 34 adult males with T2D will be randomised (1:1) to
empagliflozin or placebo once daily for 14 days as add-on to ongoing therapy. The
primary endpoints will be changes in 24-hour urinary excretion of 8-oxo-7,8
dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG)
determined before and after intervention (by ultra-performance liquid
chromatography tandem mass-spectrometry). Additionally, fasting levels of
malondialdehyde (MDA) will be determined in plasma before and after intervention
(by high-performance liquid chromatography). Further, the plasma levels of iron,
transferrin, transferrin-saturation, and ferritin are determined to correlate the
iron metabolism to the markers of oxidative modifications. ETHICS AND
DISSEMINATION: The study protocol has been approved by the Regional Committee on
Biomedical Research Ethics (approval number H-16017433), the Danish Medicines
Agency, and the Danish Data Protection Agency, and will be carried out under the
surveillance and guidance of the GCP unit at Bispebjerg Frederiksberg Hospital,
University of Copenhagen in compliance with the ICH-GCP guidelines and in
accordance with the Declaration of Helsinki. The results of this study will be
presented at national and international conferences, and submitted to a peer
reviewed international journal with authorship in accordance with Internation
Committee of Medical Journal Editors (ICMJE) Recommendations state. TRIAL
REGISTRATION: Study name: EMPOX; Pre-results: clinicaltrials.gov (NCT02890745).
Protocol version 5.1 - August, 2016.
PMID- 28490558
TI - Health status and needs of cancer survivors attending the Sydney Survivorship
Centre clinics and programmes: a protocol for longitudinal evaluation of the
centre's services.
AB - INTRODUCTION: The care of cancer survivors after primary adjuvant treatment is
recognised as a distinct phase of the cancer journey. Recent research highlights
the importance of lifestyle factors in treating symptoms, potentially decreasing
risk of a cancer recurrence and modifying the risk of developing other chronic
illnesses that are increased in the cancer population. Survivorship services aim
to deliver care that addresses these issues. The overall aims are to determine
the health status of cancer survivors and to evaluate the services offered by the
Sydney Survivorship Centre (SSC). METHODS AND ANALYSIS: This is an observational
single-centre study evaluating the longitudinal physical and psychological
health, symptoms, quality of life and lifestyle (physical activity and nutrition)
of early stage cancer survivors attending the multidisciplinary Sydney
Survivorship Clinic and survivors (at any stage of the cancer journey) and
caregivers participating in SSC courses. Evaluation of patient satisfaction is
included. Patient-reported outcomes and patient characteristics will be
summarised using descriptive statistics with Spearman rank sum correlation
coefficients to determine associations between patient-reported outcomes.
Regression modelling may be used to further evaluate associations and to
investigate risk factors and predictors of health outcomes. Qualitative data will
be analysed using thematic analysis to identify themes. Sample size will be
determined by attendance of consenting patients at clinics and courses. ETHICS
AND DISSEMINATION: The study has received ethics approval from the Concord
Repatriation General Hospital Human Research Ethics Committee (HREC/14/CRGH/23).
The results will be published and presented at appropriate conferences.This study
will provide important information regarding the health status and needs of
Australian cancer survivors and the ability of the survivorship centre to address
these needs. These data will shape the future direction of survivorship care in
Australia and facilitate the design of interventions or measures to provide
better quality of care to this patient population.
PMID- 28490559
TI - Screening for coronary artery disease in patients with type 2 diabetes: a meta
analysis and trial sequential analysis.
AB - OBJECTIVE: To evaluate the efficacy of coronary artery disease screening in
asymptomatic patients with type 2 diabetes and assess the statistical reliability
of the findings. METHODS: Electronic databases (MEDLINE, EMBASE, Cochrane Library
and clinicaltrials.org) were reviewed up to July 2016. Randomised controlled
trials evaluating coronary artery disease screening in asymptomatic patients with
type 2 diabetes and reporting cardiovascular events and/or mortality were
included. Data were summarised with Mantel-Haenszel relative risk. Trial
sequential analysis (TSA) was used to evaluate the optimal sample size to detect
a 40% reduction in outcomes. Main outcomes were all-cause mortality and cardiac
events (non-fatal myocardial infarction and cardiovascular death); secondary
outcomes were non-fatal myocardial infarction, myocardial revascularisations and
heart failure. RESULTS: One hundred thirty-five references were identified and 5
studies fulfilled the inclusion criteria and totalised 3315 patients, 117 all
cause deaths and 100 cardiac events. Screening for coronary artery disease was
not associated with decrease in risk for all-cause deaths (RR 0.95(95% CI 0.66 to
1.35)) or cardiac events (RR 0.72(95% CI 0.49 to 1.06)). TSA shows that futility
boundaries were reached for all-cause mortality and a relative risk reduction of
40% between treatments could be discarded. However, there is not enough
information for firm conclusions for cardiac events. For secondary outcomes no
benefit or harm was identified; optimal sample sizes were not reached.
CONCLUSION: Current available data do not support screening for coronary artery
disease in patients with type 2 diabetes for preventing fatal events. Further
studies are needed to assess the effects on cardiac events. PROSPERO:
CRD42015026627.
PMID- 28490560
TI - Nursing home team-care deprescribing study: a stepped-wedge randomised controlled
trial protocol.
AB - INTRODUCTION: An ageing population has become an urgent concern for Asia in
recent times. In nursing homes, polypharmacy has also become a compounding issue.
Deprescribing practice is an evidence-based strategy to provide a better outcome
in this group of patients; however, its implementation in nursing homes is often
challenging, and prospective outcome data on deprescribing practice in the
elderly is lacking. Our study assesses the implementation of team-care
deprescribing to understand the benefits of this practice in geriatric setting
and to explore the factors affecting deprescribing practice. METHODS AND
ANALYSIS: This multicentre prospective study consists of a prestudy interview
questionnaire, and a preintervention and postintervention study to be conducted
in the nursing home setting on residents at least 65 years old and on five or
more medications. We will employ a cluster randomised stepped-wedge
interventional design, based on a five-step (reviewing, checking, discussion,
communication and documentation) team-care deprescribing practice coupled with
the use of a deprescribing guide (consisting of Beers and STOPP criteria, as well
as drug interaction checking), to assess the health and pharmacoeconomic outcome
in nursing homes' practice. Primary outcome measures of the intervention will
consist of fall risks using a fall risk assessment tool. Other outcomes assessed
include fall rates, pill burden including number of pills per day, number of
doses per day and number of medications prescribed. Cost-related measures will
include the use of cost-benefit analysis, which is calculated from the medication
cost savings from deprescribing. For the prestudy interview questionnaire,
findings will be analysed qualitatively using thematic analysis. ETHICS AND
DISSEMINATION: This study is approved by the Domain Specific Review Board of
National Healthcare Group, Singapore (2016/00422) and Monash University Human
Research Ethics Committee (2016-1430-7791). The study findings shall be
disseminated in international conferences and peer-reviewed publications. The
study is registered with ClinicalTrials.gov (NCT02863341), Pre-results.
PMID- 28490561
TI - Four-year nationwide incidence of retinitis pigmentosa in South Korea: a
population-based retrospective study from 2011 to 2014.
AB - OBJECTIVE: To determine the incidence of retinitis pigmentosa (RP) in South
Korea. DESIGN: Nationwide, population-based retrospective study. SETTING: Census
population of South Korea PARTICIPANTS: This study involved the entire population
of South Korea (n=47 990 761). Patients confirmed as having RP by an
ophthalmologist from 1 January 2011 to 31 December 2014 were included. PRIMARY
OUTCOME MEASURE: The average incidence of RP during the 4-year study period was
estimated using population data from the 2010 Korean census. RESULTS: A total of
3144 (1567 men and 1577 women) patients confirmed as having RP were identified.
The average incidence of RP was 1.64 cases/100 000 person-years (95% CI 1.58 to
1.70). The incidence of RP distribution skewed to the left across age groups,
with one smaller peak observed in the 20-24-year-old age group (1.24 cases/100
000 person-years) and a larger peak observed in the 65-69-year-old age group
(3.26 cases/100 000 person-years). The overall incidence was similar in men and
women (1.64 cases/100 000 person-years (95% CI 1.56 to 1.73) for men; 1.63
cases/100 000 person-years (95% CI 1.55 to 1.72) for women). CONCLUSIONS: Our
study's estimates of the nationwide population-based incidence of RP in an Asian
population will help advance the understanding of the disease onset and allow
healthcare systems to plan accordingly.
PMID- 28490562
TI - Autism spectrum disorder: updated prevalence and comparison of two birth cohorts
in a nationally representative Australian sample.
AB - OBJECTIVES: This study aimed to (1) provide an update on the prevalence of parent
reported autism spectrum disorder (ASD) diagnosis and new information about
teacher-reported ASD in two nationally representative Australian cohorts at ages
10-11 years, (2) examine differences in cohort demographic and clinical profiles
and (3) compare the prevalence of teacher-reported ASD and any changes in
categorisation over time across the cohorts. DESIGN: Secondary analyses were
undertaken using data from the Longitudinal Study of Australian Children (LSAC).
PARTICIPANTS: Children were recruited at kindergarten age (K cohort; birth year
1999/2000) and birth (B cohort; birth year 2003/2004), with follow-up of every 2
years for six waves. PRIMARY OUTCOME MEASURES: Parent-reported and teacher
reported ASD diagnosis was ascertained at three time points (waves 4-6). RESULTS:
At age 10-11 years, the adjusted prevalence of parent-reported ASD diagnosis was
3.9% (95% CI 3.2 to 4.5) and 2.4% (95% CI 1.6 to 2.9) in the B and K cohorts,
respectively. Teacher-reported prevalence of ASD was 1.7% (95% CI 1.2 to 2.1) in
the B cohort and 0.9% (95% CI 0.56 to 1.14) in the K cohort. Parents reported
fewer conduct and peer problems and teachers more pro-social behaviour in B
relative to K cohort ASD children. Children reported only by parents in the later
born B cohort had milder behaviour problems than parent-agreed and teacher-agreed
cases. Although individual switching to ASD from other categories from 8-9 to 10
11 years was low (K cohort n=5, B cohort n=6), teachers reported more children
with ASD in the B than K cohort at 10-11 years and fewer children with emotional/
behavioural problems. CONCLUSIONS: The higher prevalence of parent-reported and
teacher-reported ASD diagnosis in the later-born cohort may be partially
explained by identifying children with milder behavioural problems as ASD and a
change in the use of diagnostic categories in schools.
PMID- 28490563
TI - Are medical outliers associated with worse patient outcomes? A retrospective
study within a regional NHS hospital using routine data.
AB - OBJECTIVE: To explore the quality and safety of patients' healthcare provision by
identifying whether being a medical outlier is associated with worse patient
outcomes. A medical outlier is a hospital inpatient who is classified as a
medical patient for an episode within a spell of care and has at least one non
medical ward placement within that spell. DATA SOURCES: Secondary data from the
Patient Administration System of a district general hospital were provided for
the financial years 2013/2014-2015/2016. The data included 71 038 medical patient
spells for the 3-year period. STUDY DESIGN: This research was based on a
retrospective, cross-sectional observational study design. Multivariate logistic
regression and zero-truncated negative binomial regression were used to explore
patient outcomes (in-hospital mortality, 30-day mortality, readmissions and
length of stay (LOS)) while adjusting for several confounding factors. PRINCIPAL
FINDINGS: Univariate analysis indicated that an outlying medical in-hospital
patient has higher odds for readmission, double the odds of staying longer in the
hospital but no significant difference in the odds of in-hospital and 30-day
mortality. Multivariable analysis indicates that being a medical outlier does not
affect mortality outcomes or readmission, but it does prolong LOS in the
hospital. CONCLUSIONS: After adjusting for other factors, medical outliers are
associated with an increased LOS while mortality or readmissions are not worse
than patients treated in appropriate specialty wards. This is in line with
existing but limited literature that such patients experience worse patient
outcomes. Hospitals may need to revisit their policies regarding outlying
patients as increased LOS is associated with an increased likelihood of harm
events, worse quality of care and increased healthcare costs.
PMID- 28490564
TI - Association between serum osmolarity and mortality in patients who are critically
ill: a retrospective cohort study.
AB - OBJECTIVES: This research aims to explore the association between serum
osmolarity and mortality in patients who are critically ill with specific
categories of disease. DESIGN: A retrospective cohort study. SETTING AND
PARTICIPANTS: Data were extracted from an online database named 'Multiparameter
Intelligent Monitoring in Intensive Care II'. 16 598 patients were included.
METHODS: Patients were divided into six disease subgroups based on the diagnosis
at admission: cardiac, cerebral, vascular, gastrointestinal, respiratory and non
respiratory. The association between maximum osmolarity (osmolaritymax) and
hospital mortality in each subgroup was evaluated using osmolaritymax as a design
variable (six levels). RESULTS: Analysis of the 16 598 patients revealed a 'U'
shaped relationship between osmolarity and mortality with a threshold of 300
mmoL/L. For patients with non-respiratory disease, both hypo-osmolarity and
hyperosmolaritymax were associated with increased mortality, with the OR
increasing from osmolaritymax level 3 (OR: 1.98, 95% CI 1.69 to 2.33, p<0.001) to
level 6 (OR: 4.45, 95% CI 3.58 to 5.53, p<0.001), using level 2 (290-309 mmoL/L)
as the reference group. For patients with respiratory disease, however, neither
hypo-osmolarity nor hyperosmolaritymax was significantly associated with
mortality (levels 1 to 5) except for extreme hyperosmolaritymax (>=340 mmoL/L,
OR: 2.03, 95% CI 1.20 to 3.42, p=0.007). ORs of mortality in the other four
subgroups (cardiac, cerebral, vascular, gastrointestinal) were similar, with OR
progressively increasing from level 3 to 6. In all six subgroups, vasopressin use
was consistently associated with increased mortality. CONCLUSIONS:
Hyperosmolarity is associated with increased mortality in patients who are
critically ill with cardiac, cerebral, vascular and gastrointestinal admission
diagnoses, with thresholds at 300 mmoL/L. For patients with respiratory disease,
however, no significant association was detected.
PMID- 28490565
TI - Efficacy and safety of ipragliflozin and metformin for visceral fat reduction in
patients with type 2 diabetes receiving treatment with dipeptidyl peptidase-4
inhibitors in Japan: a study protocol for a prospective, multicentre, blinded
endpoint phase IV randomised controlled trial (PRIME-V study).
AB - INTRODUCTION: In Japan, dipeptidyl peptidase-4 (DPP-4) inhibitors are frequently
used as the treatment of choice for patients with type 2 diabetes. In some cases,
however, poor glycaemic and body weight control issues persist despite treatment
with DPP-4 inhibitors. Previous researchers have revealed that sodium-dependent
glucose transporter-2 (SGLT-2) inhibitors reduce both plasma glucose levels and
body weight in patients with type 2 diabetes. However, further investigation
regarding the effects of SGLT-2 inhibitors on body composition, especially in the
Asian population who tends to have relatively low-to-moderate body mass indices,
is required. Therefore, we aim to determine the effects of treatment with SGLT-2
inhibitors or metformin for reducing visceral fat in 106 Asian patients with type
2 diabetes who were undergoing treatment with the DPP-4 inhibitor sitagliptin (50
mg daily) for poor glycaemic control. METHODS AND ANALYSIS: A prospective,
multicentre, blinded-endpoint phase IV randomised controlled study will be
conducted to evaluate the safety and efficacy of a 24-week treatment with either
an SGLT-2 inhibitor (ipragliflozin) or metformin for reducing visceral fat and
plasma glucose levels in patients with type 2 diabetes. Patients who satisfy the
eligibility criteria will be randomised (1:1) to receive ipragliflozin (50 mg
daily) or metformin (1000 mg daily). The primary outcome is the rate of change in
the total area of visceral fat for patients in both treatment groups, measured
using CT, after 24 weeks of therapy. Two radiologists, blinded to the clinical
information, will perform centralised analysis of the images in a unified
measurement condition. ETHICS AND DISSEMINATION: The protocol was approved by the
institutional review board of each hospital. This study is ongoing and due to
finish in April 2017. The findings of this study will be disseminated via peer
reviewed publications and conference presentations, and will also be disseminated
to participants. TRIAL REGISTRATION NUMBER: UMIN000015170, R000016861
(https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000016861); Pre
results.
PMID- 28490566
TI - A retrospective cohort study of the utility of the modified early warning score
for interfacility transfer of patients with traumatic injury.
AB - OBJECTIVE: The modified early warning score (MEWS) is a 'track and trigger' score
using routine physiological vital signs. The objective is to determine if the
pretransfer MEWS can be used for predicting outcomes in trauma patients requiring
interfacility transfer to higher levels of care. DESIGN, SETTING AND
PARTICIPANTS: Retrospective study of consecutively transferred trauma patients
into a level-II trauma centre from 2013 to 2014. INTERVENTIONS: None. OUTCOME
MEASURES: Mortality, intensive care unit (ICU) admission, operative procedure,
MEWS deterioration in-transit, air transport interfacility, secondary overtriage
(low injury severity score (ISS) <10, LOS<1 day, discharged home) and severe
injury (ISS >=16). The association between the pretransfer MEWS and outcomes were
analysed with Cochran-Armitage trend tests, receiver operator characteristic
(ROC) curves and univariate logistic regression. RESULTS: There were 587
transferred patients; outcomes were reported in 339 patients with complete data
on all five vital signs used to calculate the MEWS. The MEWS ranged from 0 to 9
(median of 1). There was a significant linear relationship between MEWS and study
outcomes, especially mortality, ICU admission, air medical transport and severe
injury (p<0.001 for all). A threshold score >=4 was identified by ROC analysis;
11.2% of patients had MEWS >=4. Outcomes were significantly worse in patients
with MEWS >=4 versus <4: mortality (26.2% vs 3.0%, OR=11.59, p<0.001); ICU
admission (73.7% vs 47.2%, OR=3.14, p=0.003); air transfer (42.1% vs 15.6%,
OR=3.93, p<0.001) and severe injury (59.5% vs 27.2%, OR=3.9, p<0.001). The MEWS
was not associated with surgery, in-transit MEWS deterioration or secondary
overtriage. CONCLUSION: Pretransfer MEWS >=4 may be used by the receiving
facility for predicting injury severity, mortality, air transport and ICU
resource use. In the interfacility transport setting, the MEWS may be useful for
identifying patients with less obvious need for transfer or requiring more
expeditious transfer.
PMID- 28490567
TI - Validity and reliability of the Patient Centred Assessment Method for patient
complexity and relationship with hospital length of stay: a prospective cohort
study.
AB - OBJECTIVES: Several instruments for evaluating patient complexity have been
developed from a biopsychosocial perspective. Although relationships between the
results obtained by these instruments and the length of stay in hospital have
been examined, many instruments are complicated and not easy to use. The Patient
Centred Assessment Method (PCAM) is a candidate for practical use. This study
aimed to test the validity and reliability of the PCAM and examine the
correlations between length of hospital stay and PCAM scores in a regional
secondary care hospital in Japan. DESIGN: Prospective cohort study. PARTICIPANTS
AND SETTING: Two hundred and one patients admitted to Ouji Coop Hospital between
July 2014 and September 2014. MAIN PREDICTOR: PCAM total score in initial phase
of hospital admission. MAIN OUTCOME: Length of stay in hospital. RESULTS: Among
201 patients (Female/Male=98/103) with mean (SD) age of 77.4+/-11.9 years, the
mean PCAM score was 25+/-7.3 and mean (SD) length of stay in hospital (LOS)
34.1+/-40.9 days. Using exploratory factor analysis to examine construct
validity, PCAM evidently has a two-factor structure, comprising medicine-oriented
and patient-oriented complexity. The Spearman rank correlation coefficient for
evaluating criterion-based validity between PCAM and INTERMED was 0.90. For
reliability, Cronbach's alpha was 0.85. According to negative binomial regression
analyses, PCAM scores are a statistically significant predictor (p<0.001) of LOS
after adjusting for age, gender, Mini Nutritional Assessment Short-Form, Charlson
Comorbidity Index, serum sodium concentration, total number of medications and
whether public assistance was required. In another model, each factor in PCAM was
independently correlated with length of stay in hospital after adjustment
(medicine-oriented complexity: p=0.001, patient-oriented complexity: p=0.014).
CONCLUSION: PCAM is a reliable and valid measurement of patient complexity and
PCAM scores have a significant correlation with hospital length of stay.
PMID- 28490568
TI - Noninvasive detection of F8 int22h-related inversions and sequence variants in
maternal plasma of hemophilia carriers.
AB - Direct detection of F8 and F9 sequence variants in maternal plasma of hemophilia
carriers has been demonstrated by microfluidics digital PCR. Noninvasive prenatal
assessment of the most clinically relevant group of sequence variants among
patients with hemophilia, namely, those involving int22h-related inversions
disrupting the F8 gene, poses additional challenges because of its molecular
complexity. We investigated the use of droplet digital PCR (ddPCR) and targeted
massively parallel sequencing (MPS) for maternal plasma DNA analysis to
noninvasively determine fetal mutational status in pregnancies at risk for
hemophilia. We designed family-specific ddPCR assays to detect causative sequence
variants scattered across the F8 and F9 genes. A haplotype-based approach coupled
with targeted MPS was applied to deduce fetal genotype by capturing a 7.6-Mb
region spanning the F8 gene in carriers with int22h-related inversions. The ddPCR
analysis correctly determined fetal hemophilia status in 15 at-risk pregnancies
in samples obtained from 8 to 42 weeks of gestation. There were 3 unclassified
samples, but no misclassification. Detailed fetal haplotype maps of the F8 gene
region involving int22h-related inversions obtained through targeted MPS enabled
correct diagnoses of fetal mutational status in 3 hemophilia families. Our data
suggest it is feasible to apply targeted MPS to interrogate maternally inherited
F8 int22h-related inversions, whereas ddPCR represents an affordable approach for
the identification of F8 and F9 sequence variants in maternal plasma. These
advancements may bring benefits for the pregnancy management for carriers of
hemophilia sequence variants; in particular, the common F8 int22h-related
inversions, associated with the most severe clinical phenotype.
PMID- 28490569
TI - Safety and tolerability of pembrolizumab in patients with relapsed/refractory
primary mediastinal large B-cell lymphoma.
AB - Treatment options for relapsed/refractory primary mediastinal large B-cell
lymphoma (rrPMBCL) are limited, and prognosis is generally poor (overall response
rate [ORR] 0% to 25%; 2-year overall survival 15%). PMBCL frequently involves PD
1 ligand overexpression, potentially making PMBCL particularly susceptible to PD
1 blockade. We evaluated safety and antitumor activity of pembrolizumab, an anti
PD-1 antibody, in rrPMBCL as part of the KEYNOTE-013 multicohort phase 1b trial.
At time of data cutoff, 18 patients (median age 30 years; median 3 prior lines of
therapy) had been enrolled and treated, of whom 17 were included in the efficacy
analyses. Eleven patients (61%) experienced drug-related adverse events (mostly
grade 1-2); none discontinued treatment due to adverse events. ORR was 41%
(7/17); 6 additional patients (35%) had stable disease. Of patients evaluable by
imaging, 13 out of 16 (81%) had decreases in target lesions. With a median follow
up of 11.3 months, median duration of response was not reached. Two patients
reached the maximum 2-year treatment duration and remain in remission. Median
overall survival was not reached for treated patients overall; all responders
were still alive at data cutoff. These results in heavily pretreated rrPMBCL
patients demonstrate that PD-1 blockade with pembrolizumab has a manageable
safety profile and promising antitumor activity. This trial was registered at
www.clinicaltrials.gov as #NCT01953692.
PMID- 28490571
TI - Evaluating a CLL susceptibility variant in ITGB2 in families with multiple
subtypes of hematological malignancies.
PMID- 28490570
TI - Mouse RUNX1C regulates premegakaryocytic/erythroid output and maintains survival
of megakaryocyte progenitors.
AB - RUNX1 is crucial for the regulation of megakaryocyte specification, maturation,
and thrombopoiesis. Runx1 possesses 2 promoters: the distal P1 and proximal P2
promoters. The major protein isoforms generated by P1 and P2 are RUNX1C and
RUNX1B, respectively, which differ solely in their N-terminal amino acid
sequences. RUNX1C is the most abundantly expressed isoform in adult
hematopoiesis, present in all RUNX1-expressing populations, including the cKit+
hematopoietic stem and progenitor cells. RUNX1B expression is more restricted,
being highly expressed in the megakaryocyte lineage but downregulated during
erythropoiesis. We generated a Runx1 P1 knock-in of RUNX1B, termed P1-MRIPV This
mouse line lacks RUNX1C expression but has normal total RUNX1 levels, solely
comprising RUNX1B. Using this mouse line, we establish a specific requirement for
the P1-RUNX1C isoform in megakaryopoiesis, which cannot be entirely compensated
for by RUNX1B overexpression. P1 knock-in megakaryocyte progenitors have reduced
proliferative capacity and undergo increased cell death, resulting in
thrombocytopenia. P1 knock-in premegakaryocyte/erythroid progenitors demonstrate
an erythroid-specification bias, evident from increased erythroid colony-forming
ability and decreased megakaryocyte output. At a transcriptional level, multiple
erythroid-specific genes are upregulated and megakaryocyte-specific transcripts
are downregulated. In addition, proapoptotic pathways are activated in P1 knock
in premegakaryocyte/erythroid progenitors, presumably accounting for the
increased cell death in the megakaryocyte progenitor compartment. Unlike in the
conditional adult Runx1 null models, megakaryocytic maturation is not affected in
the P1 knock-in mice, suggesting that RUNX1B can regulate endomitosis and
thrombopoiesis. Therefore, despite the high degree of structural similarity,
RUNX1B and RUNX1C isoforms have distinct and specific roles in adult
megakaryopoiesis.
PMID- 28490572
TI - Heterogeneous resistance to quizartinib in acute myeloid leukemia revealed by
single-cell analysis.
AB - Genomic studies have revealed significant branching heterogeneity in cancer.
Studies of resistance to tyrosine kinase inhibitor therapy have not fully
reflected this heterogeneity because resistance in individual patients has been
ascribed to largely mutually exclusive on-target or off-target mechanisms in
which tumors either retain dependency on the target oncogene or subvert it
through a parallel pathway. Using targeted sequencing from single cells and
colonies from patient samples, we demonstrate tremendous clonal diversity in the
majority of acute myeloid leukemia (AML) patients with activating FLT3 internal
tandem duplication mutations at the time of acquired resistance to the FLT3
inhibitor quizartinib. These findings establish that clinical resistance to
quizartinib is highly complex and reflects the underlying clonal heterogeneity of
AML.
PMID- 28490573
TI - DOK7 gene therapy enhances motor activity and life span in ALS model mice.
AB - Amyotrophic lateral sclerosis (ALS) is a progressive, multifactorial motor
neurodegenerative disease with severe muscle atrophy. The glutamate release
inhibitor riluzole is the only medication approved by the FDA, and prolongs
patient life span by a few months, testifying to a strong need for new treatment
strategies. In ALS, motor neuron degeneration first becomes evident at the motor
nerve terminals in neuromuscular junctions (NMJs), the cholinergic synapse
between motor neuron and skeletal muscle; degeneration then progresses
proximally, implicating the NMJ as a therapeutic target. We previously
demonstrated that activation of muscle-specific kinase MuSK by the cytoplasmic
protein Dok-7 is essential for NMJ formation, and forced expression of Dok-7 in
muscle activates MuSK and enlarges NMJs. Here, we show that therapeutic
administration of an adeno-associated virus vector encoding the human DOK7 gene
suppressed motor nerve terminal degeneration at NMJs together with muscle atrophy
in the SOD1-G93A ALS mouse model. Ultimately, we show that DOK7 gene therapy
enhanced motor activity and life span in ALS model mice.
PMID- 28490574
TI - Early Emergence of CD19-Negative Human Antibody-Secreting Cells at the
Plasmablast to Plasma Cell Transition.
AB - Long-lived human plasma cells (PCs) play central roles in immunity and
autoimmunity and are enriched among the subpopulation of CD19neg human PCs.
However, whether human CD19neg PCs are necessarily aged cells that have gradually
lost CD19 expression is not known. Assessing peripheral blood samples at steady
state and during the acute response to influenza vaccination in healthy donors,
we identify the presence of phenotypic CD19neg plasmablasts, the proliferative
precursor state to mature PCs, and demonstrate by ELISPOT that these are Ab
secreting cells (ASCs). During the acute response to influenza vaccination,
CD19pos, CD19low, and CD19neg ASCs secrete vaccine-specific Abs and show linked
IGHV repertoires. To address precursor/product relationships, we use in vitro
models that mimic T-dependent and T-independent differentiation, finding that the
CD19neg state can be established at the plasmablast to PC transition, that
CD19neg PCs increase as a percentage of surviving PCs in vitro, and that CD19neg
and CD19pos PCs can be maintained independently. These data provide proof-of
principle for the view that newly generated ASCs can acquire a mature PC
phenotype that is accompanied by loss of CD19 expression at an early stage of
differentiation and that aging is not an obligate requirement for a CD19neg state
to be established.
PMID- 28490575
TI - EZH2 Regulates the Developmental Timing of Effectors of the Pre-Antigen Receptor
Checkpoints.
AB - The histone methyltransferase EZH2 is required for B and T cell development;
however, the molecular mechanisms underlying this requirement remain elusive. In
a murine model of lymphoid-specific EZH2 deficiency we found that EZH2 was
required for proper development of adaptive, but not innate, lymphoid cells. In
adaptive lymphoid cells EZH2 prevented the premature expression of Cdkn2a and the
consequent stabilization of p53, an effector of the pre-Ag receptor checkpoints.
Deletion of Cdkn2a in EZH2-deficient lymphocytes prevented p53 stabilization,
extended lymphocyte survival, and restored differentiation resulting in the
generation of mature B and T lymphocytes. Our results uncover a crucial role for
EZH2 in adaptive lymphocytes to control the developmental timing of effectors of
the pre-Ag receptor checkpoints.
PMID- 28490576
TI - Complement C5a Functions as a Master Switch for the pH Balance in Neutrophils
Exerting Fundamental Immunometabolic Effects.
AB - During sepsis, excessive activation of the complement system with generation of
the anaphylatoxin C5a results in profound disturbances in crucial neutrophil
functions. Moreover, because neutrophil activity is highly dependent on
intracellular pH (pHi), we propose a direct mechanistic link between complement
activation and neutrophil pHi In this article, we demonstrate that in vitro
exposure of human neutrophils to C5a significantly increased pHi by selective
activation of the sodium/hydrogen exchanger. Upstream signaling of C5a-mediated
intracellular alkalinization was dependent on C5aR1, intracellular calcium,
protein kinase C, and calmodulin, and downstream signaling regulated the release
of antibacterial myeloperoxidase and lactoferrin. Notably, the pH shift caused by
C5a increased the glucose uptake and activated glycolytic flux in neutrophils,
resulting in a significant release of lactate. Furthermore, C5a induced
acidification of the extracellular micromilieu. In experimental murine sepsis,
pHi of blood neutrophils was analogously alkalinized, which could be normalized
by C5aR1 inhibition. In the clinical setting of sepsis, neutrophils from patients
with septic shock likewise exhibited a significantly increased pHi These data
suggest a novel role for the anaphylatoxin C5a as a master switch of the delicate
pHi balance in neutrophils resulting in profound inflammatory and metabolic
changes that contribute to hyperlactatemia during sepsis.
PMID- 28490577
TI - Five minutes with . . . Kate Lovett.
PMID- 28490580
TI - What is the overlap between HIV and shigellosis epidemics in England: further
evidence of MSM transmission?
AB - BACKGROUND: Evidence suggests that sexual transmission between men has replaced
foreign travel as the predominant mode of Shigella transmission in England.
However, sexuality and HIV status are not routinely recorded for laboratory
reported Shigella, and the role of HIV in the Shigella epidemic is not well
understood. METHODS: The Modular Open Laboratory Information System containing
all Shigella cases reported to Public Health England (PHE) and the PHE HIV and
AIDS Reporting System holding all adults living with diagnosed HIV in England
were matched using a combination of Soundex code, date of birth and gender.
RESULTS: From 2004 to 2015, 88 664 patients were living with HIV, and 10 269
Shigella cases were reported in England; 9% (873/10 269) of Shigella cases were
diagnosed with HIV, of which 93% (815/873) were in men. Shigella cases without
reported travel history were more likely to be living with HIV than those who had
travelled (14% (751/5427) vs 3% (134/4854); p<0.01). From 2004 to 2015, the
incidence of Shigella in men with HIV rose from 47/100 000 to 226/100 000
(p<0.01) peaking in 2014 at 265/100 000, but remained low in women throughout the
study period (0-24/100 000). Among Shigella cases without travel and with HIV,
91% (657/720) were men who have sex with men (MSM). HIV preceded Shigella
diagnosis in 86% (610/720), and 65% (237/362) had an undetectable viral load (<50
copies/mL). DISCUSSION: We observed a sustained increase in the national rate of
shigellosis in MSM with HIV, who may experience more serious clinical disease.
Sexual history, HIV status and STI risk might require sensitive investigation in
men presenting with gastroenteritis.
PMID- 28490582
TI - Congenital Human Cytomegalovirus Infection and the Enigma of Maternal Immunity.
AB - Human cytomegalovirus (HCMV) is the most common viral infection acquired by the
developing human fetus and can result in damage to the developing central nervous
system. Although vaccine development to modify this congenital infection is
ongoing, the unique epidemiology of maternal HCMV infections appears discordant
with strategies for vaccine development. Several characteristics of congenital
HCMV infections suggest that the efficacy of vaccines designed to induce
responses similar to those that follow natural infection will be limited.
PMID- 28490581
TI - Patterns of prevalent HPV and STI co-infections and associated factors among HIV
negative young Western Cape, South African women: the EVRI trial.
AB - OBJECTIVE: To estimate the prevalence and describe the patterns of concurrent
human papillomavirus (HPV) and STIs and associated factors among HIV-negative
young Western Cape, South African women participating in the Efficacy of HPV
Vaccine to Reduce HIV Infection (EVRI) trial. METHODS: HIV-negative women aged 16
24 years old were enrolled in the EVRI trial (NCT01489527) and randomised to
receive the licensed four-valent HPV vaccine or placebo. At study entry,
participants were clinically evaluated for five STIs: herpes simplex virus type 2
(HSV-2), chlamydia, gonorrhoea, syphilis and disease-causing HPV genotypes
(6/11/16/18/31/33/35/39/45/51/52/56/58/59/68). Demographic and sexual history
characteristics were compared among women with STI co-infections, single
infection and no infection using Pearson chi2 and Mann-Whitney tests. ORs were
calculated to evaluate factors associated with STI co-infection prevalence.
RESULTS: Among 388 young women, STI co-infection prevalence was high: 47% had >=2
concurrent STIs, 36% had a single STI and 17% had none of the five evaluated
STIs. HPV/HSV-2 (26%) was the most prevalent co-infection detected followed by
HPV/HSV-2/Chlamydia trachomatis (CT) (17%) and HPV/CT (15%). Co-infection
prevalence was independently associated with alcohol use (adjusted OR=2.01, 95%
CI 1.00 to 4.06) and having a sexual partner with an STI (adjusted OR=6.96, 95%
CI 1.53 to 30.08). CONCLUSIONS: Among high-risk young women from underserved
communities such as in Southern Africa, a multicomponent prevention strategy that
integrates medical and behavioural interventions targeting both men and women is
essential to prevent acquisition of concurrent STI infections and consequent
disease. TRIAL REGISTRATION NUMBER: NCT01489527; Post-results.
PMID- 28490578
TI - Investigating Clinical Issues by Genotyping of Medically Important Fungi: Why and
How?
AB - Genotyping studies of medically important fungi have addressed elucidation of
outbreaks, nosocomial transmissions, infection routes, and genotype-phenotype
correlations, of which secondary resistance has been most intensively
investigated. Two methods have emerged because of their high discriminatory power
and reproducibility: multilocus sequence typing (MLST) and microsatellite length
polymorphism (MLP) using short tandem repeat (STR) markers. MLST relies on single
nucleotide polymorphisms within the coding regions of housekeeping genes. STR
polymorphisms are based on the number of repeats of short DNA fragments, mostly
outside coding regions, and thus are expected to be more polymorphic and more
rapidly evolving than MLST markers. There is no consensus on a universal typing
system. Either one or both of these approaches are now available for Candida
spp., Aspergillus spp., Fusarium spp., Scedosporium spp., Cryptococcus
neoformans, Pneumocystis jirovecii, and endemic mycoses. The choice of the method
and the number of loci to be tested depend on the clinical question being
addressed. Next-generation sequencing is becoming the most appropriate method for
fungi with no MLP or MLST typing available. Whatever the molecular tool used,
collection of clinical data (e.g., time of hospitalization and sharing of similar
rooms) is mandatory for investigating outbreaks and nosocomial transmission.
PMID- 28490583
TI - Structural Definition of Duck Major Histocompatibility Complex Class I Molecules
That Might Explain Efficient Cytotoxic T Lymphocyte Immunity to Influenza A
Virus.
AB - A single dominantly expressed allele of major histocompatibility complex class I
(MHC I) may be responsible for the duck's high tolerance to highly pathogenic
influenza A virus (HP-IAV) compared to the chicken's lower tolerance. In this
study, the crystal structures of duck MHC I (Anpl-UAA*01) and duck beta2
microglobulin (beta2m) with two peptides from the H5N1 strains were determined.
Two remarkable features were found to distinguish the Anpl-UAA*01 complex from
other known MHC I structures. A disulfide bond formed by Cys95 and Cys112 and
connecting the beta5 and beta6 sheets at the bottom of peptide binding groove
(PBG) in Anpl-UAA*01 complex, which can enhance IAV peptide binding, was
identified. Moreover, the interface area between duck MHC I and beta2m was found
to be larger than in other species. In addition, the two IAV peptides that
display distinctive conformations in the PBG, B, and F pockets act as the primary
anchor sites. Thirty-one IAV peptides were used to verify the peptide binding
motif of Anpl-UAA*01, and the results confirmed that the peptide binding motif is
similar to that of HLA-A*0201. Based on this motif, approximately 600 peptides
from the IAV strains were partially verified as the candidate epitope peptides
for Anpl-UAA*01, which is a far greater number than those for chicken BF2*2101
and BF2*0401 molecules. Extensive IAV peptide binding should allow for ducks with
this Anpl-UAA*01 haplotype to resist IAV infection.IMPORTANCE Ducks are natural
reservoirs of influenza A virus (IAV) and are more resistant to the IAV than
chickens. Both ducks and chickens express only one dominant MHC I locus providing
resistance to the virus. To investigate how MHC I provides IAV resistance,
crystal structures of the dominantly expressed duck MHC class I (pAnpl-UAA*01)
with two IAV peptides were determined. A disulfide bond was identified in the
peptide binding groove that can facilitate Anpl-UAA*01 binding to IAV peptides.
Anpl-UAA*01 has a much wider recognition spectrum of IAV epitope peptides than do
chickens. The IAV peptides bound by Anpl-UAA*01 display distinctive conformations
that can help induce an extensive cytotoxic T lymphocyte (CTL) response. In
addition, the interface area between the duck MHC I and beta2m is larger than in
other species. These results indicate that HP-IAV resistance in ducks is due to
extensive CTL responses induced by MHC I.
PMID- 28490584
TI - A Naturally Occurring Recombinant Enterovirus Expresses a Torovirus
Deubiquitinase.
AB - Enteroviruses (EVs) are implicated in a wide range of diseases in humans and
animals. In this study, a novel enterovirus (enterovirus species G [EVG]) (EVG
08/NC_USA/2015) was isolated from a diagnostic sample from a neonatal pig
diarrhea case and identified by using metagenomics and complete genome
sequencing. The viral genome shares 75.4% nucleotide identity with a prototypic
EVG strain (PEV9 UKG/410/73). Remarkably, a 582-nucleotide insertion, flanked by
3Cpro cleavage sites at the 5' and 3' ends, was found in the 2C/3A junction
region of the viral genome. This insertion encodes a predicted protease with 54
to 68% amino acid identity to torovirus (ToV) papain-like protease (PLP) (ToV
PLP). Structural homology modeling predicts that this protease adopts a fold and
a catalytic site characteristic of minimal PLP catalytic domains. This structure
is similar to those of core catalytic domains of the foot-and-mouth disease virus
leader protease and coronavirus PLPs, which act as deubiquitinating and
deISGylating (interferon [IFN]-stimulated gene 15 [ISG15]-removing) enzymes on
host cell substrates. Importantly, the recombinant ToV-PLP protein derived from
this novel enterovirus also showed strong deubiquitination and deISGylation
activities and demonstrated the ability to suppress IFN-beta expression. Using
reverse genetics, we generated a ToV-PLP knockout recombinant virus. Compared to
the wild-type virus, the ToV-PLP knockout mutant virus showed impaired growth and
induced higher expression levels of innate immune genes in infected cells. These
results suggest that ToV-PLP functions as an innate immune antagonist;
enterovirus G may therefore gain fitness through the acquisition of ToV-PLP from
a recombination event.IMPORTANCE Enteroviruses comprise a highly diversified
group of viruses. Genetic recombination has been considered a driving force for
viral evolution; however, recombination between viruses from two different orders
is a rare event. In this study, we identified a special case of cross-order
recombination between enterovirus G (order Picornavirales) and torovirus (order
Nidovirales). This naturally occurring recombination event may have broad
implications for other picornaviral and/or nidoviral species. Importantly, we
demonstrated that the exogenous ToV-PLP gene that was inserted into the EVG
genome encodes a deubiquitinase/deISGylase and potentially suppresses host
cellular innate immune responses. Our results provide insights into how a gain of
function through genetic recombination, in particular cross-order recombination,
may improve the ability of a virus to evade host immunity.
PMID- 28490585
TI - Cross-Linking of a CD4-Mimetic Miniprotein with HIV-1 Env gp140 Alters Kinetics
and Specificities of Antibody Responses against HIV-1 Env in Macaques.
AB - Evaluation of the epitope specificities, locations (systemic or mucosal), and
effector functions of antibodies elicited by novel HIV-1 immunogens engineered to
improve exposure of specific epitopes is critical for HIV-1 vaccine development.
Utilizing an array of humoral assays, we evaluated the magnitudes, epitope
specificities, avidities, and functions of systemic and mucosal immune responses
elicited by a vaccine regimen containing Env cross-linked to a CD4-mimetic
miniprotein (gp140-M64U1) in rhesus macaques. Cross-linking of gp140 Env to M64U1
resulted in earlier increases of both the magnitude and avidity of the IgG
binding response than those with Env protein alone. Notably, IgG binding
responses at an early time point correlated with antibody-dependent cellular
cytotoxicity (ADCC) function at the peak immunity time point, which was higher
for the cross-linked Env group than for the Env group. In addition, the cross
linked Env group developed higher IgG responses against a linear epitope in the
gp120 C1 region of the HIV-1 envelope glycoprotein. These data demonstrate that
structural modification of the HIV-1 envelope immunogen by cross-linking of gp140
with the CD4-mimetic M64U1 elicited an earlier increase of binding antibody
responses and altered the specificity of the IgG responses, correlating with the
rise of subsequent antibody-mediated antiviral functions.IMPORTANCE The
development of an efficacious HIV-1 vaccine remains a global priority to prevent
new cases of HIV-1 infection. Of the six HIV-1 efficacy trials to date, only one
has demonstrated partial efficacy, and immune correlate analysis of that trial
revealed a role for binding antibodies and antibody Fc-mediated effector
functions. New HIV-1 envelope immunogens are being engineered to selectively
expose the most vulnerable and conserved sites on the HIV-1 envelope, with the
goal of eliciting antiviral antibodies. Evaluation of the humoral responses
elicited by these novel immunogen designs in nonhuman primates is critical for
understanding how to improve upon immunogen design to inform further testing in
human clinical trials. Our results demonstrate that structural modifications of
Env that aim to mimic the CD4-bound conformation can result in earlier antibody
elicitation, altered epitope specificity, and increased antiviral function
postimmunization.
PMID- 28490586
TI - Deletion of the K1L Gene Results in a Vaccinia Virus That Is Less Pathogenic Due
to Muted Innate Immune Responses, yet Still Elicits Protective Immunity.
AB - All viruses strategically alter the antiviral immune response to their benefit.
The vaccinia virus (VACV) K1 protein has multiple immunomodulatory effects in
tissue culture models of infection, including NF-kappaB antagonism. However, the
effect of K1 during animal infection is poorly understood. We determined that a
K1L-less vaccinia virus (vDeltaK1L) was less pathogenic than wild-type VACV in
intranasal and intradermal models of infection. Decreased pathogenicity was
correlated with diminished virus replication in intranasally infected mice.
However, in intradermally inoculated ears, vDeltaK1L replicated to levels nearly
identical to those of VACV, implying that the decreased immune response to
vDeltaK1L infection, not virus replication, dictated lesion size. Several lines
of evidence support this theory. First, vDeltaK1L induced slightly less edema
than vK1L, as revealed by histopathology and noninvasive quantitative ultrasound
technology (QUS). Second, infiltrating immune cell populations were decreased in
vDeltaK1L-infected ears. Third, cytokine and chemokine gene expression was
decreased in vDeltaK1L-infected ears. While these results identified the
biological basis for smaller lesions, they remained puzzling; because K1
antagonizes NF-kappaB in vitro, antiviral gene expression was expected to be
higher during vDeltaK1L infection. Despite these diminished innate immune
responses, vDeltaK1L vaccination induced a protective VACV-specific CD8+ T cell
response and protected against a lethal VACV challenge. Thus, vDeltaK1L is the
first vaccinia virus construct reported that caused a muted innate immune gene
expression profile and decreased immune cell infiltration in an intradermal model
of infection yet still elicited protective immunity.IMPORTANCE The vaccinia virus
(VACV) K1 protein inhibits NF-kappaB activation among its other antagonistic
functions. A virus lacking K1 (vDeltaK1L) was predicted to be less pathogenic
because it would trigger a more robust antiviral immune response than VACV.
Indeed, vDeltaK1L was less pathogenic in intradermally infected mouse ear pinnae.
However, vDeltaK1L infection unexpectedly elicited dramatically reduced
infiltration of innate immune cells into ears. This was likely due to decreased
expression of cytokine and chemokine genes in vDeltaK1L-infected ears. As such,
our finding contradicted observations from cell culture systems. Interestingly,
vDeltaK1L conferred protective immunity against lethal VACV challenge. This
suggests that the muted immune response triggered during vDeltaK1L infection
remained sufficient to mount an effective protective response. Our results
highlight the complexity and unpredictable nature of virus-host interactions, a
relationship that must be understood to better comprehend virus pathogenesis or
to manipulate viruses for use as vaccines.
PMID- 28490579
TI - Bartonella Species, an Emerging Cause of Blood-Culture-Negative Endocarditis.
AB - Since the reclassification of the genus Bartonella in 1993, the number of species
has grown from 1 to 45 currently designated members. Likewise, the association of
different Bartonella species with human disease continues to grow, as does the
range of clinical presentations associated with these bacteria. Among these,
blood-culture-negative endocarditis stands out as a common, often undiagnosed,
clinical presentation of infection with several different Bartonella species. The
limitations of laboratory tests resulting in this underdiagnosis of Bartonella
endocarditis are discussed. The varied clinical picture of Bartonella infection
and a review of clinical aspects of endocarditis caused by Bartonella are
presented. We also summarize the current knowledge of the molecular basis of
Bartonella pathogenesis, focusing on surface adhesins in the two Bartonella
species that most commonly cause endocarditis, B. henselae and B. quintana. We
discuss evidence that surface adhesins are important factors for autoaggregation
and biofilm formation by Bartonella species. Finally, we propose that biofilm
formation is a critical step in the formation of vegetative masses during
Bartonella-mediated endocarditis and represents a potential reservoir for
persistence by these bacteria.
PMID- 28490587
TI - Heparanase Upregulation Contributes to Porcine Reproductive and Respiratory
Syndrome Virus Release.
AB - Porcine reproductive and respiratory syndrome virus (PRRSV) continues to cause
substantial economic losses to the pig industry worldwide. Heparan sulfate (HS)
is used by PRRSV for initial attachment to target cells. However, the role of HS
in the late phase of PRRSV infection and the mechanism of virus release from host
cells remain largely unknown. In this study, we showed that PRRSV infection
caused a decrease in HS expression and upregulated heparanase, the only known
enzyme capable of degrading HS. We subsequently demonstrated that the NF-kappaB
signaling pathway and cathepsin L protease were involved in regulation of PRRSV
infection-induced heparanase. In addition, we found that ablation of heparanase
expression using small interfering RNA duplexes increased cell surface expression
of HS and suppressed PRRSV replication and release, whereas overexpression of
heparanase reduced HS surface expression and enhanced PRRSV replication and
release. These data suggest that PRRSV activates NF-kappaB and cathepsin L to
upregulate and process heparanase, and then the active heparanase cleaves HS,
resulting in viral release. Our findings provide new insight into the molecular
mechanism of PRRSV egress from host cells, which might help us to further
understand PRRSV pathogenesis.IMPORTANCE Porcine reproductive and respiratory
syndrome virus (PRRSV) causes great economic losses each year to the pig industry
worldwide. The molecular mechanism of PRRSV release from host cells largely
remains a mystery. In this study, we demonstrate that PRRSV activates NF-kappaB
and cathepsin L to upregulate and process heparanase, and then the active
heparanase is released to the extracellular space and exerts enzymatic activity
to cleave heparan sulfate, resulting in viral release. Our findings provide new
insight into the molecular mechanism of PRRSV egress from host cells, which might
help us to further understand PRRSV pathogenesis.
PMID- 28490588
TI - Induction of a Tier-1-Like Phenotype in Diverse Tier-2 Isolates by Agents That
Guide HIV-1 Env to Perturbation-Sensitive, Nonnative States.
AB - The envelope glycoproteins (Envs) on the surfaces of HIV-1 particles are targeted
by host antibodies. Primary HIV-1 isolates demonstrate different global
sensitivities to antibody neutralization; tier-1 isolates are sensitive, whereas
tier-2 isolates are more resistant. Single-site mutations in Env can convert tier
2 into tier-1-like viruses. We hypothesized that such global change in
neutralization sensitivity results from weakening of intramolecular interactions
that maintain Env integrity. Three strategies commonly applied to perturb protein
structure were tested for their effects on global neutralization sensitivity:
exposure to low temperature, Env-activating ligands, and a chaotropic agent. A
large panel of diverse tier-2 isolates from clades B and C was analyzed.
Incubation at 0 degrees C, which globally weakens hydrophobic interactions,
causes gradual and reversible exposure of the coreceptor-binding site. In the
cold-induced state, Envs progress at isolate-specific rates to unstable forms
that are sensitive to antibody neutralization and then gradually lose function.
Agents that mimic the effects of CD4 (CD4Ms) also induce reversible structural
changes to states that exhibit isolate-specific stabilities. The chaotropic agent
urea (at low concentrations) does not affect the structure or function of native
Env. However, urea efficiently perturbs metastable states induced by cold and
CD4Ms and increases their sensitivity to antibody neutralization and their
inactivation rates Therefore, chemical and physical agents can guide Env from the
stable native state to perturbation-sensitive forms and modulate their stability
to bestow tier-1-like properties on primary tier-2 strains. These concepts can be
applied to enhance the potency of vaccine-elicited antibodies and microbicides at
mucosal sites of HIV-1 transmission.IMPORTANCE An effective vaccine to prevent
transmission of HIV-1 is a primary goal of the scientific and health care
communities. Vaccine-elicited antibodies target the viral envelope glycoproteins
(Envs) and can potentially inhibit infection. However, the potency of such
antibodies is generally low. Single-site mutations in Env can enhance the global
sensitivity of HIV-1 to neutralization by antibodies. We found that such a
hypersensitivity phenotype can also be induced by agents that destabilize protein
structure. Exposure to 0 degrees C or low concentrations of Env-activating
ligands gradually guides Env to metastable forms that expose cryptic epitopes and
that are highly sensitive to neutralization. Low concentrations of the chaotropic
agent urea do not affect native Env but destabilize perturbed states induced by
cold or CD4Ms and increase their neutralization. The concept of enhancing
antibody sensitivity by chemical agents that affect the structural stability of
proteins can be applied to increase the potency of topical microbicides and
vaccine-elicited antibodies.
PMID- 28490589
TI - Roles of M1 and M2 Macrophages in Herpes Simplex Virus 1 Infectivity.
AB - Macrophages are the predominant infiltrate in the corneas of mice that have been
ocularly infected with herpes simplex virus 1 (HSV-1). However, very little is
known about the relative roles of M1 (classically activated or polarized) and M2
(alternatively activated or polarized) macrophages in ocular HSV-1 infection. To
better understand these relationships, we assessed the impact of directed M1 or
M2 activation of RAW264.7 macrophages and peritoneal macrophages (PM) on
subsequent HSV-1 infection. In both the RAW264.7 macrophage and PM in vitro
models, HSV-1 replication in M1 macrophages was markedly lower than in M2
macrophages and unstimulated controls. The M1 macrophages expressed significantly
higher levels of 28 of the 32 tested cytokines and chemokines than M2
macrophages, with HSV-1 infection significantly increasing the levels of
proinflammatory cytokines and chemokines in the M1 versus the M2 macrophages. To
examine the effects of shifting the immune response toward either M1 or M2
macrophages in vivo, wild-type mice were injected with gamma interferon (IFN
gamma) DNA or colony-stimulating factor 1 (CSF-1) DNA prior to ocular infection
with HSV-1. Virus replication in the eye, latency in trigeminal ganglia (TG), and
markers of T cell exhaustion in the TG were determined. We found that injection
of mice with IFN-gamma DNA, which enhances the development of M1 macrophages,
increased virus replication in the eye; increased latency; and also increased
CD4, CD8, IFN-gamma, and PD-1 transcripts in the TG of latently infected mice.
Conversely, injection of mice with CSF-1 DNA, which enhances the development of
M2 macrophages, was associated with reduced virus replication in the eye and
reduced latency and reduced the levels of CD4, CD8, IFN-gamma,and PD-1
transcripts in the TG. Collectively, these results suggest that M2 macrophages
directly reduce the levels of HSV-1 latency and, thus, T-cell exhaustion in the
TG of ocularly infected mice.IMPORTANCE Our findings demonstrate a novel approach
to further reducing HSV-1 replication in the eye and latency in the TG by
modulating immune components, specifically, by altering the phenotype of
macrophages. We suggest that inclusion of CSF-1 as part of any vaccination
regimen against HSV infection to coax responses of macrophages toward an M2,
rather than an M1, response may further improve vaccine efficacy against ocular
HSV-1 replication and latency.
PMID- 28490590
TI - The C Terminus of the Herpes Simplex Virus UL25 Protein Is Required for Release
of Viral Genomes from Capsids Bound to Nuclear Pores.
AB - The herpes simplex virus (HSV) capsid is released into the cytoplasm after fusion
of viral and host membranes, whereupon dynein-dependent trafficking along
microtubules targets it to the nuclear envelope. Binding of the capsid to the
nuclear pore complex (NPC) is mediated by the capsid protein pUL25 and the capsid
tethered tegument protein pUL36. Temperature-sensitive mutants in both pUL25 and
pUL36 dock at the NPC but fail to release DNA. The uncoating reaction has been
difficult to study due to the rapid release of the genome once the capsid
interacts with the nuclear pore. In this study, we describe the isolation and
characterization of a truncation mutant of pUL25. Live-cell imaging and
immunofluorescence studies demonstrated that the mutant was not impaired in
penetration of the host cell or in trafficking of the capsid to the nuclear
membrane. However, expression of viral proteins was absent or significantly
delayed in cells infected with the pUL25 mutant virus. Transmission electron
microscopy revealed capsids accumulated at nuclear pores that retained the viral
genome for at least 4 h postinfection. In addition, cryoelectron microscopy (cryo
EM) reconstructions of virion capsids did not detect any obvious differences in
the location or structural organization for the pUL25 or pUL36 proteins on the
pUL25 mutant capsids. Further, in contrast to wild-type virus, the antiviral
response mediated by the viral DNA-sensing cyclic guanine adenine synthase (cGAS)
was severely compromised for the pUL25 mutant. These results demonstrate that the
pUL25 capsid protein has a critical role in releasing viral DNA from NPC-bound
capsids.IMPORTANCE Herpes simplex virus 1 (HSV-1) is the causative agent of
several pathologies ranging in severity from the common cold sore to life
threatening encephalitic infection. Early steps in infection include release of
the capsid into the cytoplasm, docking of the capsid at a nuclear pore, and
release of the viral genome into the nucleus. A key knowledge gap is how the
capsid engages the NPC and what triggers release of the viral genome into the
nucleus. Here we show that the C-terminal region of the HSV-1 pUL25 protein is
required for releasing the viral genome from capsids docked at nuclear pores. The
significance of our research is in identifying pUL25 as a key viral factor for
genome uncoating. pUL25 is found at each of the capsid vertices as part of the
capsid vertex-specific component and implicates the importance of this complex
for NPC binding and genome release.
PMID- 28490591
TI - Deletion of a 197-Amino-Acid Region in the N-Terminal Domain of Spike Protein
Attenuates Porcine Epidemic Diarrhea Virus in Piglets.
AB - We previously isolated a porcine epidemic diarrhea virus (PEDV) strain, PC177, by
blind serial passaging of the intestinal contents of a diarrheic piglet in Vero
cell culture. Compared with the highly virulent U.S. PEDV strain PC21A, the
tissue culture-adapted PC177 (TC-PC177) contains a 197-amino-acid (aa) deletion
in the N-terminal domain of the spike (S) protein. We orally inoculated neonatal,
conventional suckling piglets with TC-PC177 or PC21A to compare their
pathogenicities. Within 7 days postinoculation, TC-PC177 caused mild diarrhea and
lower fecal viral RNA shedding, with no mortality, whereas PC21A caused severe
clinical signs and 55% mortality. To investigate whether infection with TC-PC177
can induce cross-protection against challenge with a highly virulent PEDV strain,
all the surviving piglets were challenged with PC21A at 3 weeks postinoculation.
Compared with 100% protection in piglets initially inoculated with PC21A, 88% and
100% TC-PC177- and mock-inoculated piglets had diarrhea following challenge,
respectively, indicating incomplete cross-protection. To investigate whether this
197-aa deletion was the determinant for the attenuation of TC-PC177, we generated
a mutant (icPC22A-S1Delta197) bearing the 197-aa deletion from an infectious cDNA
clone of the highly virulent PEDV PC22A strain (infectious clone PC22A, icPC22A).
In neonatal gnotobiotic pigs, the icPC22A-S1Delta197 virus caused mild to
moderate diarrhea, lower titers of viral shedding, and no mortality, whereas the
icPC22A virus caused severe diarrhea and 100% mortality. Our data indicate that
deletion of this 197-aa fragment in the spike protein can attenuate a highly
virulent PEDV, but the virus may lose important epitopes for inducing robust
protective immunity.IMPORTANCE The emerging, highly virulent PEDV strains have
caused substantial economic losses worldwide. However, the virulence determinants
are not established. In this study, we found that a 197-aa deletion in the N
terminal region of the S protein did not alter virus (TC-PC177) tissue tropism
but reduced the virulence of the highly virulent PEDV strain PC22A in neonatal
piglets. We also demonstrated that the primary infection with TC-PC177 failed to
induce complete cross-protection against challenge by the highly virulent PEDV
PC21A, suggesting that the 197-aa region may contain important epitopes for
inducing protective immunity. Our results provide an insight into the role of
this large deletion in virus propagation and pathogenicity. In addition, the
reverse genetics platform of the PC22A strain was further optimized for the
rescue of recombinant PEDV viruses in vitro This breakthrough allows us to
investigate other virulence determinants of PEDV strains and will provide
knowledge leading to better control PEDV infections.
PMID- 28490592
TI - Epstein-Barr Virus Rta-Mediated Accumulation of DNA Methylation Interferes with
CTCF Binding in both Host and Viral Genomes.
AB - Rta, an Epstein-Barr virus (EBV) immediate-early protein, reactivates viral lytic
replication that is closely associated with tumorigenesis. In previous studies,
we demonstrated that in epithelial cells Rta efficiently induced cellular
senescence, which is an irreversible G1 arrest likely to provide a favorable
environment for productive replications of EBV and Kaposi's sarcoma-associated
herpesvirus (KSHV). To restrict progression of the cell cycle, Rta simultaneously
upregulates CDK inhibitors and downregulates MYC, CCND1, and JUN, among others.
Rta has long been known as a potent transcriptional activator, thus its role in
gene repression is unexpected. In silico analysis revealed that the promoter
regions of MYC, CCND1, and JUN are common in (i) the presence of CpG islands,
(ii) strong chromatin immunoprecipitation (ChIP) signals of CCCTC-binding factor
(CTCF), and (iii) having at least one Rta binding site. By combining ChIP assays
and DNA methylation analysis, here we provide evidence showing that Rta binding
accumulated CpG methylation and decreased CTCF occupancy in the regulatory
regions of MYC, CCND1, and JUN, which were associated with downregulated gene
expression. Stable residence of CTCF in the viral latency and reactivation
control regions is a hallmark of viral latency. Here, we observed that Rta
mediated decreased binding of CTCF in the viral genome is concurrent with virus
reactivation. Via interfering with CTCF binding, in the host genome Rta can
function as a transcriptional repressor for gene silencing, while in the viral
genome Rta acts as an activator for lytic gene loci by removing a topological
constraint established by CTCF.IMPORTANCE CTCF is a multifunctional protein that
variously participates in gene expression and higher-order chromatin structure of
the cellular and viral genomes. In certain loci of the genome, CTCF occupancy and
DNA methylation are mutually exclusive. Here, we demonstrate that the Epstein
Barr virus (EBV) immediate-early protein, Rta, known to be a transcriptional
activator, can also function as a transcriptional repressor. Via enriching CpG
methylation and decreasing CTCF reloading, Rta binding efficiently shut down the
expression of MYC, CCND1, and JUN, thus impeding cell cycle progression. Rta
mediated disruption of CTCF binding was also detected in the latency/reactivation
control regions of the EBV genome, and this in turn led to viral lytic cycle
progression. As emerging evidence indicates that a methylated EBV genome is a
preferable substrate for EBV Zta, the other immediate-early protein, our results
suggest a mechanistic link in understanding the molecular processes of viral
latent-lytic switch.
PMID- 28490593
TI - Evolution and Antiviral Specificities of Interferon-Induced Mx Proteins of Bats
against Ebola, Influenza, and Other RNA Viruses.
AB - Bats serve as a reservoir for various, often zoonotic viruses, including
significant human pathogens such as Ebola and influenza viruses. However, for
unknown reasons, viral infections rarely cause clinical symptoms in bats. A tight
control of viral replication by the host innate immune defense might contribute
to this phenomenon. Transcriptomic studies revealed the presence of the
interferon-induced antiviral myxovirus resistance (Mx) proteins in bats, but
detailed functional aspects have not been assessed. To provide evidence that bat
Mx proteins might act as key factors to control viral replication we cloned Mx1
cDNAs from three bat families, Pteropodidae, Phyllostomidae, and
Vespertilionidae. Phylogenetically these bat Mx1 genes cluster closely with their
human ortholog MxA. Using transfected cell cultures, minireplicon systems, virus
like particles, and virus infections, we determined the antiviral potential of
the bat Mx1 proteins. Bat Mx1 significantly reduced the polymerase activity of
viruses circulating in bats, including Ebola and influenza A-like viruses. The
related Thogoto virus, however, which is not known to infect bats, was not
inhibited by bat Mx1. Further, we provide evidence for positive selection in bat
Mx1 genes that might explain species-specific antiviral activities of these
proteins. Together, our data suggest a role for Mx1 in controlling these viruses
in their bat hosts.IMPORTANCE Bats are a natural reservoir for various viruses
that rarely cause clinical symptoms in bats but are dangerous zoonotic pathogens,
like Ebola or rabies virus. It has been hypothesized that the interferon system
might play a key role in controlling viral replication in bats. We speculate that
the interferon-induced Mx proteins might be key antiviral factors of bats and
have coevolved with bat-borne viruses. This study evaluated for the first time a
large set of bat Mx1 proteins spanning three major bat families for their
antiviral potential, including activity against Ebola virus and bat influenza A
like virus, and we describe here their phylogenetic relationship, revealing
patterns of positive selection that suggest a coevolution with viral pathogens.
By understanding the molecular mechanisms of the innate resistance of bats
against viral diseases, we might gain important insights into how to prevent and
fight human zoonotic infections caused by bat-borne viruses.
PMID- 28490594
TI - Dok-1 and Dok-2 Are Required To Maintain Herpes Simplex Virus 1-Specific CD8+ T
Cells in a Murine Model of Ocular Infection.
AB - Dok-1 and Dok-2 negatively regulate responses downstream of several immune
receptors in lymphoid and myeloid cells. Recent evidence showed that Dok proteins
are essential in the formation of memory CD8+ T cells to an exogenous epitope
expressed by vaccinia virus; however, the importance of Dok-1 and Dok-2 in the
control of viral infection is unknown. Here, we investigated the role of Dok
proteins in modulating the immune response against herpes simplex virus 1 (HSV-1)
in a mouse model of ocular infection. During acute infection, viral titers in the
eye were similar in wild-type (WT) and Dok-1 and Dok-2 double-knockout (DKO)
mice, and the percentages of infiltrating leukocytes were similar in DKO and WT
corneas and trigeminal ganglia (TG). DKO mice exhibited a diminished CD8+ T cell
response to the immunodominant HSV-1 glycoprotein B (gB) epitope in the spleen
and draining lymph nodes compared to WT mice during acute infection. Remarkably,
gB-specific CD8+ T cells almost completely disappeared in the spleens of DKO mice
during latency, and the reduction of CD8+ effector memory T (Tem) cells was more
severe than that of CD8+ central memory T (Tcm) cells. The percentage of gB
specific CD8+ T cells in TG during latency was also dramatically reduced in DKO
mice; however, they were phenotypically similar to those from WT mice. In ex vivo
assays, reactivation was detected earlier in TG cultures from infected DKO versus
WT mice. Thus, Dok-1 and Dok-2 promote survival of gB-specific CD8+ T cells in TG
latently infected with HSV-1.IMPORTANCE HSV-1 establishes lifelong latency in
sensory neurons of trigeminal ganglia (TG). In humans, HSV-1 is able to
sporadically reactivate from latently infected neurons and establish a lytic
infection at a site to which the neurons project. Most herpetic disease in humans
is due to reactivation of HSV-1 from latency rather than to primary acute
infection. CD8+ T cells are thought to play an important role in controlling
recurrent infections. In this study, we examined the involvement of Dok-1 and Dok
2 signaling proteins in the control of HSV-1 infection. We provide evidence that
Dok proteins are required to maintain a CD8+ T cell response against HSV-1 during
latency-especially CD8+ Tem cells-and that they negatively affect HSV-1
reactivation from latency. Elucidating Dok-mediated mechanisms involved in the
control of HSV-1 reactivation from latency might contribute to the development of
therapeutic strategies to prevent recurrent HSV-1-induced pathology.
PMID- 28490595
TI - Sensing of HIV-1 Entry Triggers a Type I Interferon Response in Human Primary
Macrophages.
AB - Along with CD4+ T lymphocytes, macrophages are a major cellular source of HIV-1
replication and a potential viral reservoir. Following entry and reverse
transcription in macrophages, cloaking of the viral cDNA by the HIV-1 capsid
limits its cytosolic detection, enabling efficient replication. However, whether
incoming HIV-1 particles are sensed by macrophages prior to reverse transcription
remains unclear. Here, we show that HIV-1 triggers a broad expression of
interferon (IFN)-stimulated genes (ISG) in monocyte-derived macrophages within a
few hours after infection. This response does not require viral reverse
transcription or the presence of HIV-1 RNA within particles, but viral fusion is
essential. This response is elicited by viruses carrying different envelope
proteins and thus different receptors to proceed for viral entry. Expression of
ISG in response to viral entry requires TBK1 activity and type I IFNs signaling.
Remarkably, the ISG response is transient but affects subsequent viral spread.
Together, our results shed light on an early step of HIV-1 sensing by macrophages
at the level of entry, which confers an early protection through type I IFN
signaling and has potential implications in controlling the infection.IMPORTANCE
HIV infection is restricted to T lymphocytes and macrophages. HIV-1-infected
macrophages are found in many tissues of infected patients, even under
antiretroviral therapy, and are considered a viral reservoir. How HIV-1 is
detected and what type of responses are elicited upon sensing remain in great
part elusive. The kinetics and localization of the production of cytokines such
as interferons in response to HIV is of critical importance to understanding how
the infection and the immune response are established. Our study provides
evidence that macrophages can detect HIV-1 as soon as it enters the cell.
Interestingly, this sensing is independent of the presence of viral nucleic acids
within the particles but requires their fusion with the macrophages. This
triggers a low interferon response, which activates an antiviral program
protecting cells against further viral challenge and thus potentially limiting
the spread of the infection.
PMID- 28490596
TI - Deletion of the Vaccinia Virus I2 Protein Interrupts Virion Morphogenesis,
Leading to Retention of the Scaffold Protein and Mislocalization of Membrane
Associated Entry Proteins.
AB - The I2L open reading frame of vaccinia virus (VACV) encodes a conserved 72-amino
acid protein with a putative C-terminal transmembrane domain. Previous studies
with a tetracycline-inducible mutant demonstrated that I2-deficient virions are
defective in cell entry. The purpose of the present study was to determine the
step of replication or entry that is affected by loss of the I2 protein.
Fluorescence microscopy experiments showed that I2 colocalized with a major
membrane protein of immature and mature virions. We generated a cell line that
constitutively expressed I2 and allowed construction of the VACV I2L deletion
mutant vDeltaI2. As anticipated, vDeltaI2 was unable to replicate in cells that
did not express I2. Unexpectedly, morphogenesis was interrupted at a stage after
immature virion formation, resulting in the accumulation of dense spherical
particles instead of brick-shaped mature virions with well-defined core
structures. The abnormal particles retained the D13 scaffold protein of immature
virions, were severely deficient in the transmembrane proteins that comprise the
entry fusion complex (EFC), and had increased amounts of unprocessed membrane and
core proteins. Total lysates of cells infected with vDeltaI2 also had diminished
EFC proteins due to instability attributed to their hydrophobicity and failure to
be inserted into viral membranes. A similar instability of EFC proteins had
previously been found with unrelated mutants blocked earlier in morphogenesis
that also accumulated viral membranes retaining the D13 scaffold. We concluded
that I2 is required for virion morphogenesis, release of the D13 scaffold, and
the association of EFC proteins with viral membranes.IMPORTANCE Poxviruses
comprise a large family that infect vertebrates and invertebrates, cause disease
in both in humans and in wild and domesticated animals, and are being engineered
as vectors for vaccines and cancer therapy. In addition, investigations of
poxviruses have provided insights into many aspects of cell biology. The I2
protein is conserved in all poxviruses that infect vertebrates, suggesting an
important role. The present study revealed that this protein is essential for
vaccinia virus morphogenesis and that its absence results in an accumulation of
deformed virus particles retaining the scaffold protein and deficient in surface
proteins needed for cell entry.
PMID- 28490597
TI - Molluscum Contagiosum Virus Protein MC005 Inhibits NF-kappaB Activation by
Targeting NEMO-Regulated IkappaB Kinase Activation.
AB - Molluscum contagiosum virus (MCV), the only known extant human-adapted poxvirus,
causes a long-duration infection characterized by skin lesions that typically
display an absence of inflammation despite containing high titers of live virus.
Despite this curious presentation, MCV is very poorly characterized in terms of
host-pathogen interactions. The absence of inflammation around MCV lesions
suggests the presence of potent inhibitors of human antiviral immunity and
inflammation. However, only a small number of MCV immunomodulatory genes have
been characterized in detail. It is likely that many more remain to be
discovered, given the density of such sequences in other poxvirus genomes. NF
kappaB activation occurs in response to both virus-induced pattern recognition
receptor (PRR) signaling and cellular activation by virus-induced proinflammatory
cytokines like tumor necrosis factor and interleukin-1. Activated NF-kappaB
drives cytokine and interferon gene expression, leading to inflammation and virus
clearance. We report that MC005, which has no orthologs in other poxvirus
genomes, is a novel inhibitor of PRR- and cytokine-stimulated NF-kappaB
activation. MC005 inhibited NF-kappaB proximal to the IkappaB kinase (IKK)
complex, and unbiased affinity purification revealed that MC005 interacts with
the IKK subunit NEMO (NF-kappaB essential modulator). MC005 binding to NEMO
prevents the conformational priming of the IKK complex that occurs when NEMO
binds to ubiquitin chains during pathway activation. These data reveal a novel
mechanism of poxvirus inhibition of human innate immunity, validate current
dynamic models of NEMO-dependent IKK complex activation, and further clarify how
the human-adapted poxvirus MCV can so effectively evade antiviral immunity and
suppress inflammation to persist in human skin lesions.IMPORTANCE Poxviruses
adapt to specific hosts over time, evolving and tailoring elegantly precise
inhibitors of the rate-limiting steps within the signaling pathways that control
innate immunity and inflammation. These inhibitors reveal new features of the
antiviral response, clarify existing models of signaling regulation while
offering potent new tools for approaching therapeutic intervention in
autoimmunity and inflammatory disease. Molluscum contagiosum virus (MCV) is the
only known extant poxvirus specifically adapted to human infection and appears
adept at evading normal human antiviral responses, yet it remains poorly
characterized. We report the identification of MCV protein MC005 as an inhibitor
of the pathways leading to the activation of NF-kappaB, an essential regulator of
innate immunity. Further, identification of the mechanism of inhibition of NF
kappaB by MC005 confirms current models of the complex way in which NF-kappaB is
regulated and greatly expands our understanding of how MCV so effectively evades
human immunity.
PMID- 28490598
TI - Development of Clade-Specific and Broadly Reactive Live Attenuated Influenza
Virus Vaccines against Rapidly Evolving H5 Subtype Viruses.
AB - We have developed pandemic live attenuated influenza vaccines (pLAIVs) against
clade 1 H5N1 viruses on an Ann Arbor cold-adapted (ca) backbone that induced long
term immune memory. In 2015, many human infections caused by a new clade (clade
2.2.1.1) of goose/Guangdong (gs/GD) lineage H5N1 viruses were reported in Egypt,
which prompted updating of the H5N1 pLAIV. We explored two strategies to generate
suitable pLAIVs. The first approach was to modify the hemagglutinin gene of a
highly pathogenic wild-type (wt) clade 2.2.1.1 virus, A/Egypt/N03434/2009
(Egy/09) (H5N1), with its unmodified neuraminidase (NA) gene; this virus was
designated Egy/09 ca The second approach was to select a low-pathogenicity avian
influenza H5 virus that elicited antibodies that cross-reacted with a broad range
of H5 viruses, including the Egypt H5N1 viruses, and contained a novel NA subtype
for humans. We selected the low-pathogenicity A/duck/Hokkaido/69/2000 (H5N3)
(dk/Hok/00) virus for this purpose. Both candidate vaccines were attenuated and
immunogenic in ferrets, inducing antibodies that neutralized homologous and
heterologous H5 viruses with different degrees of cross-reactivity; Egy/09 ca
vaccine antisera were more specific for the gs/GD lineage viruses but did not
neutralize recent North American isolates (clade 2.3.4.4), whereas antisera from
dk/Hok/69 ca-vaccinated ferrets cross-reacted with clade 2.3.4.4 and 2.2.1
viruses but not clade 1 or 2.1 viruses. When vaccinated ferrets were challenged
with homologous and heterologous H5 viruses, challenge virus replication was
reduced in the respiratory tract. Thus, the two H5 pLAIV candidates are suitable
for clinical development to protect humans from infection with different clades
of H5 viruses.IMPORTANCE In response to the continuing evolution of H5N1 avian
influenza viruses and human infections, new candidate H5 live attenuated vaccines
were developed by using two different approaches: one targeted a specific
circulating strain in Egypt, and the other was based on a virus that elicits
broadly cross-reactive antibodies against a wide range of H5 viruses. Both
candidate vaccines were immunogenic and exhibited protective efficacy in ferrets.
Our study permits a comparison of the two approaches, and the data support the
further development of both vaccine viruses to optimally prepare for the further
spread of clade 2.2.1 or 2.3.4.4 viruses.
PMID- 28490599
TI - The phenotype of SDHB germline mutation carriers: a nationwide study.
AB - OBJECTIVE: Succinate dehydrogenase B subunit (SDHB) gene germline mutations
predispose to pheochromocytomas, sympathetic paragangliomas, head and neck
paragangliomas and non-paraganglionic tumors (e.g. renal cell carcinoma,
gastrointestinal stromal tumor and pituitary neoplasia). The aim of this study
was to determine phenotypical characteristics of a large Dutch cohort of SDHB
germline mutation carriers and assess differences in clinical phenotypes related
to specific SDHB mutations. DESIGN: Retrospective descriptive study. METHODS:
Retrospective descriptive study in seven academic centers. RESULTS: We included
194 SDHB mutation carriers consisting 65 (33.5%) index patients and 129 (66.5%)
relatives. Mean age was 44.8 +/- 16.0 years. Median duration of follow-up was 2.6
years (range: 0-36). Sixty persons (30.9%) carried the exon 3 deletion and 46
(23.7%) the c.423 + 1G > A mutation. Fifty-four mutation carriers (27.8%) had one
or multiple head and neck paragangliomas, 4 (2.1%) had a pheochromocytoma and 26
(13.4%) had one or more sympathetic paragangliomas. Fifteen patients (7.7%)
developed metastatic paraganglioma and 17 (8.8%) developed non-paraganglionic
tumors. At study close, there were 111 (57.2%) unaffected mutation carriers.
Statistical analyses showed no significant differences in the number and location
of head and neck paragangliomas, sympathetic paragangliomas or pheochromocytomas,
nor in the occurrence of metastatic disease or other tumors between carriers of
the two founder SDHB mutations (exon 3 deletion vs c.423 + 1G > A). CONCLUSIONS:
In this nationwide study of disease-affected and unaffected SDHB mutation
carriers, we observed a lower rate of metastatic disease and a relatively high
number of head and neck paragangliomas compared with previously reported referral
based cohorts.
PMID- 28490600
TI - Something is definitely better than nothing: simple strategies to prevent
vascular dysfunction.
AB - Understanding the negative health consequences of a physical inactivity has been
the topic of much investigation as an alarming number of adults have adopted a
sedentary lifestyle. With the rise in sedentarism the field of inactivity
physiology has emerged. The goal of inactivity physiology is to identify the
impact in inactivity on health and develop strategies that effectively minimize
the risk of a sedentary lifestyle. Arising from this field is the finding that
excessive sitting is linked to increased cardiovascular and metabolic disease and
all-cause mortality. Most importantly, these relationships exist even in
individuals that are physically active. Clearly, excessive sitting is an
occupational hazard with significant health consequences. Through a series of
investigations, including research published this issue of Clinical Science,
Padilla and colleagues have identified that prolonged sitting evokes vascular
dysfunction and that this dysfunction is caused by reduced shear stress. This
commentary highlights this series of investigations and culminates with an
overview of how prior exercise and standing are effective strategies to
circumvent vascular dysfunction that is caused by excessive sitting.
PMID- 28490601
TI - Optimizing mating encounters by sexually dimorphic movements.
AB - All organisms with sexual reproduction undergo a process of mating, which
essentially involves the encounter of two individuals belonging to different
sexes. During mate search, both sexes should mutually optimize their encounters,
thus raising a question of how they achieve this. Here, we show that a population
with sexually dimorphic movement patterns achieves the highest individual mating
success under a limited lifespan. Extensive simulations found and analytical
approximations corroborated the existence of conditions under which sexual
dimorphism in the movement patterns (i.e. how diffusively they move) is
advantageous over sexual monomorphism. Mutual searchers with limited lifespans
need to balance the speed and accuracy of finding their mates, and dimorphic
movements can solve this trade-off. We further demonstrate that the sexual
dimorphism can evolve from an initial sexually monomorphic population. Our
results emphasize the importance of considering mutual optimization in problems
of random search.
PMID- 28490602
TI - Processes on the emergent landscapes of biochemical reaction networks and
heterogeneous cell population dynamics: differentiation in living matters.
AB - The notion of an attractor has been widely employed in thinking about the
nonlinear dynamics of organisms and biological phenomena as systems and as
processes. The notion of a landscape with valleys and mountains encoding multiple
attractors, however, has a rigorous foundation only for closed, thermodynamically
non-driven, chemical systems, such as a protein. Recent advances in the theory of
nonlinear stochastic dynamical systems and its applications to mesoscopic
reaction networks, one reaction at a time, have provided a new basis for a
landscape of open, driven biochemical reaction systems under sustained chemostat.
The theory is equally applicable not only to intracellular dynamics of
biochemical regulatory networks within an individual cell but also to tissue
dynamics of heterogeneous interacting cell populations. The landscape for an
individual cell, applicable to a population of isogenic non-interacting cells
under the same environmental conditions, is defined on the counting space of
intracellular chemical compositions x = (x1,x2, ... ,xN ) in a cell, where xl is
the concentration of the lth biochemical species. Equivalently, for heterogeneous
cell population dynamics xl is the number density of cells of the lth cell type.
One of the insights derived from the landscape perspective is that the life
history of an individual organism, which occurs on the hillsides of a landscape,
is nearly deterministic and 'programmed', while population-wise an asynchronous
non-equilibrium steady state resides mostly in the lowlands of the landscape. We
argue that a dynamic 'blue-sky' bifurcation, as a representation of Waddington's
landscape, is a more robust mechanism for a cell fate decision and subsequent
differentiation than the widely pictured pitch-fork bifurcation. We revisit, in
terms of the chemostatic driving forces upon active, living matter, the notions
of near-equilibrium thermodynamic branches versus far-from-equilibrium states.
The emergent landscape perspective permits a quantitative discussion of a wide
range of biological phenomena as nonlinear, stochastic dynamics.
PMID- 28490604
TI - The evolution of lossy compression.
AB - In complex environments, there are costs to both ignorance and perception. An
organism needs to track fitness-relevant information about its world, but the
more information it tracks, the more resources it must devote to perception. As a
first step towards a general understanding of this trade-off, we use a tool from
information theory, rate-distortion theory, to study large, unstructured
environments with fixed, randomly drawn penalties for stimuli confusion
('distortions'). We identify two distinct regimes for organisms in these
environments: a high-fidelity regime where perceptual costs grow linearly with
environmental complexity, and a low-fidelity regime where perceptual costs are,
remarkably, independent of the number of environmental states. This suggests that
in environments of rapidly increasing complexity, well-adapted organisms will
find themselves able to make, just barely, the most subtle distinctions in their
environment.
PMID- 28490603
TI - Inferring single-cell behaviour from large-scale epithelial sheet migration
patterns.
AB - Cell migration plays an important role in a wide variety of biological processes
and can incorporate both individual cell motion and collective behaviour. The
emergent properties of collective migration are receiving increasing attention as
collective motion's role in diseases such as metastatic cancer becomes clear.
Yet, how individual cell behaviour influences large-scale, multi-cell collective
motion remains unclear. In this study, we provide insight into the mechanisms
behind collective migration by studying cell migration in a spreading monolayer
of epithelial MCF10A cells. We quantify migration using particle image
velocimetry and find that cell groups have features of motion that span multiple
length scales. Comparing our experimental results to a model of collective cell
migration, we find that cell migration within the monolayer can be affected in
qualitatively different ways by cell motion at the boundary, yet it is not
necessary to introduce leader cells at the boundary or specify other large-scale
features to recapitulate this large-scale phenotype in simulations. Instead, in
our model, collective motion can be enhanced by increasing the overall activity
of the cells or by giving the cells a stronger coupling between their motion and
polarity. This suggests that investigating the activity and polarity persistence
of individual cells will add insight into the collective migration phenotypes
observed during development and disease.
PMID- 28490605
TI - Adhesion modulation using glue droplet spreading in spider capture silk.
AB - Orb web spiders use sticky capture spiral silk to retain prey in webs. Capture
spiral silk is composed of an axial fibre of flagelliform silk covered with glue
droplets that are arranged in a beads-on-a-string morphology that allows multiple
droplets to simultaneously extend and resist pull off. Previous studies showed
that the adhesion of capture silk is responsive to environmental humidity,
increasing up to an optimum humidity that varied among different spider species.
The maximum adhesion was hypothesized to occur when the viscoelasticity of the
glue optimized contributions from glue spreading and bulk cohesion. In this
study, we show how glue droplet shape during peeling contributes significantly to
capture silk adhesion. Both overspreading and underspreading of glue droplets
reduces adhesion through changes in crack propagation and failure regime.
Understanding the mechanism of stimuli-responsive adhesion of spider capture silk
will lead to new designs for smarter adhesives.
PMID- 28490607
TI - Reviewers in 2016.
PMID- 28490606
TI - Comparison of 10 murine models reveals a distinct biomechanical phenotype in
thoracic aortic aneurysms.
AB - Thoracic aortic aneurysms are life-threatening lesions that afflict young and old
individuals alike. They frequently associate with genetic mutations and are
characterized by reduced elastic fibre integrity, dysfunctional smooth muscle
cells, improperly remodelled collagen and pooled mucoid material. There is a
pressing need to understand better the compromised structural integrity of the
aorta that results from these genetic mutations and renders the wall vulnerable
to dilatation, dissection or rupture. In this paper, we compare the biaxial
mechanical properties of the ascending aorta from 10 murine models: wild-type
controls, acute elastase-treated, and eight models with genetic mutations
affecting extracellular matrix proteins, transmembrane receptors, cytoskeletal
proteins, or intracellular signalling molecules. Collectively, our data for these
diverse mouse models suggest that reduced mechanical functionality, as indicated
by a decreased elastic energy storage capability or reduced distensibility, does
not predispose to aneurysms. Rather, despite normal or lower than normal
circumferential and axial wall stresses, it appears that intramural cells in the
ascending aorta of mice prone to aneurysms are unable to maintain or restore the
intrinsic circumferential material stiffness, which may render the wall
biomechanically vulnerable to continued dilatation and possible rupture. This
finding is consistent with an underlying dysfunctional mechanosensing or
mechanoregulation of the extracellular matrix, which normally endows the wall
with both appropriate compliance and sufficient strength.
PMID- 28490608
TI - Expanding the use of flow diverters beyond their initial indication: treatment of
small unruptured aneurysms.
AB - BACKGROUND: Experience with the endovascular treatment of unruptured small
intracranial aneurysms by flow diverter devices is still limited. OBJECTIVE: To
assess the safety and efficacy of the SILK flow diverter (SFD) in the treatment
of small unruptured cerebral aneurysms (<10 mm). METHODS: We performed a
retrospective review of a prospectively maintained database of patients treated
with a SFD between July 2008 and December 2013 at 4 institutions in Spain to
identify all patients with small unruptured aneurysms (<10 mm). Data for patient
demographics, aneurysm characteristics, and technical procedures were analyzed.
Angiographic and clinical findings were recorded during the procedure and at 6-
and 12-month follow-ups. RESULTS: A total of 109 small aneurysms were treated
with a SFD in 104 patients (78 women; 26 men; mean, median, and range of age:
55.2, 57.1, and 19-80 years, respectively). A total of 60 patients were
asymptomatic (57.7%). All except 7 aneurysms (6.4%) arose from the anterior
circulation. The mean size of the aneurysms was 4.7+/-1.9 mm. At 6 months, the
neuromorbidity and neuromortality rates were 2.9% and 0.9%, respectively. Imaging
at the 12-month follow-up showed complete occlusion, neck remnants, and residual
aneurysm in 88.5% (69/78), 7.7% (6/78), and 3.3% (3/78) of cases, respectively.
No delayed hemorrhage occurred. CONCLUSIONS: The findings suggest that the
indications for SFD can be safely extended to small intracranial aneurysms.
PMID- 28490611
TI - Extracolonic cancer risk in Dutch patients with APC (adenomatous polyposis coli)
associated polyposis.
AB - BACKGROUND: Screening of patients with familial adenomatous polyposis (FAP) have
led to a substantial reduction in mortality due to colorectal cancer (CRC).
Recent guidelines suggest that surveillance of non-intestinal malignancies should
also be considered in those patients. However, the value of these surveillance
programmes is unknown. The aims of this study were (1) to assess the occurrence
of extracolonic malignancies in a large series of adenomatous polyposis coli
(APC) mutation carriers and (2) to evaluate the causes of death. METHODS: All APC
mutation carriers were selected from the Dutch polyposis registry. Data on causes
of death were collected. Pathology reports were retrieved from the Dutch
Pathology Registry. RESULTS: A total of 85 extracolonic malignancies were
diagnosed in 74 of 582 APC mutation carriers. Duodenal and skin cancers were the
most prevalent cancers. Thyroid cancer was observed in only 1.5% of the cases.
The main cause of death was cancer (59% of all deaths), with 42% due to CRC and
21% due to duodenal cancer. One patient died from thyroid cancer. The second and
third most common causes of death were cardiovascular disease (13% of all deaths)
and desmoid tumours (11% of all deaths), respectively. CONCLUSION: Extending
surveillance programmes to other cancers will not contribute significantly to the
survival of patients with FAP.
PMID- 28490610
TI - Mechanisms of Insulin Resistance in Primary and Secondary Nonalcoholic Fatty
Liver.
AB - Nonalcoholic fatty liver disease is associated with hepatic insulin resistance
and may result primarily from increased hepatic de novo lipogenesis (PRIM) or
secondarily from adipose tissue lipolysis (SEC). We studied mice with hepatocyte-
or adipocyte-specific SREBP-1c overexpression as models of PRIM and SEC. PRIM
mice featured increased lipogenic gene expression in the liver and adipose
tissue. Their selective, liver-specific insulin resistance was associated with
increased C18:1-diacylglycerol content and protein kinase Cepsilon translocation.
SEC mice had decreased lipogenesis mediated by hepatic cholesterol responsive
element-binding protein and featured portal/lobular inflammation along with
total, whole-body insulin resistance. Hepatic mitochondrial respiration
transiently increased and declined with aging along with higher muscle reactive
oxygen species production. In conclusion, hepatic insulin resistance originates
from lipotoxicity but not from lower mitochondrial capacity, which can even
transiently adapt to increased peripheral lipolysis. Peripheral insulin
resistance is prevented during increased hepatic lipogenesis only if adipose
tissue lipid storage capacity is preserved.
PMID- 28490612
TI - Pathology update to the Manchester Scoring System based on testing in over 4000
families.
AB - BACKGROUND: While the requirement for thresholds for testing for mutations in
BRCA1/2 is being questioned, they are likely to remain for individuals unaffected
by a relevant cancer. It is still useful to provide pretesting likelihoods, but
models need to take into account tumour pathology. METHODS: The Manchester
Scoring System (MSS) is a well-used, simple, paper-based model for assessing
carrier probability that already incorporates pathology data. We have used
mutation testing data from 4115 unrelated samples from affected non-Jewish
individuals alongside tumour pathology to further refine the scoring system.
RESULTS: Adding additional points for high-grade serous ovarian cancer <60
(HGSOC=+2) and adding grade score to those with triple-negative breast cancer,
while reducing the score for those with HER2+ breast cancer (-6), resulted in
significantly improved sensitivity and minor improvements in specificity to the
MSS. Sporadic HGSOC <60 years thus reached a score of 15-19 points within the 10%
grouping consistent with the 15/113-13.2% that were identified with a BRCA1/2
pathogenic variant. Validation in a population series of ovarian cancer from
Cambridge showed high sensitivity at the 10% threshold 15/17 (88.2%).
CONCLUSIONS: The new pathology-adjusted Manchester score MSS3 appears to provide
an effective and simple-to-use estimate of the 10% and 20% thresholds for BRCA1/2
likelihood. For unaffected individuals, the 20-point (20%) threshold in their
affected first-degree relative can be used to determine eligibility at the 10%
threshold.
PMID- 28490609
TI - A Genome-Wide Association Study of IVGTT-Based Measures of First-Phase Insulin
Secretion Refines the Underlying Physiology of Type 2 Diabetes Variants.
AB - Understanding the physiological mechanisms by which common variants predispose to
type 2 diabetes requires large studies with detailed measures of insulin
secretion and sensitivity. Here we performed the largest genome-wide association
study of first-phase insulin secretion, as measured by intravenous glucose
tolerance tests, using up to 5,567 individuals without diabetes from 10 studies.
We aimed to refine the mechanisms of 178 known associations between common
variants and glycemic traits and identify new loci. Thirty type 2 diabetes or
fasting glucose-raising alleles were associated with a measure of first-phase
insulin secretion at P < 0.05 and provided new evidence, or the strongest
evidence yet, that insulin secretion, intrinsic to the islet cells, is a key
mechanism underlying the associations at the HNF1A, IGF2BP2, KCNQ1, HNF1B,
VPS13C/C2CD4A, FAF1, PTPRD, AP3S2, KCNK16, MAEA, LPP, WFS1, and TMPRSS6 loci. The
fasting glucose-raising allele near PDX1, a known key insulin transcription
factor, was strongly associated with lower first-phase insulin secretion but has
no evidence for an effect on type 2 diabetes risk. The diabetes risk allele at
TCF7L2 was associated with a stronger effect on peak insulin response than on C
peptide-based insulin secretion rate, suggesting a possible additional role in
hepatic insulin clearance or insulin processing. In summary, our study provides
further insight into the mechanisms by which common genetic variation influences
type 2 diabetes risk and glycemic traits.
PMID- 28490614
TI - Value in cardiovascular care.
AB - Healthcare value, defined as health outcomes achieved relative to the costs of
care, has been proposed as a unifying approach to measure improvements in the
quality and affordability of healthcare. Although value is of increasing interest
to payers, many providers remain unfamiliar with how value differs from other
approaches to the comparison of cost and outcomes (ie, cost-effectiveness
analysis). While cost-effectiveness studies can be used by policy makers and
payers to inform decisions about coverage and reimbursement for new therapies,
the assessment of healthcare can guide improvements in the delivery of healthcare
to achieve better outcomes at lower cost. Comparison on value allows for the
identification of healthcare delivery organisations or care delivery settings
where patient outcomes have been optimised at a lower cost. Gaps remain in the
measurement of healthcare value, particularly as it relates to patient-reported
health status (symptoms, functional status and health-related quality of life).
The use of technology platforms that capture health status measures with minimal
disruption to clinical workflow (ie, web portals, automated telephonic systems
and tablets to facilitate capture outside of in-person clinical interaction) is
facilitating use of health status measures to improve clinical care and optimise
patient outcomes. Furthermore, the use of a value framework has catalysed quality
improvement efforts and research to seek better patient outcomes at lower cost.
PMID- 28490613
TI - The BRCA1 c. 5096G>A p.Arg1699Gln (R1699Q) intermediate risk variant: breast and
ovarian cancer risk estimation and recommendations for clinical management from
the ENIGMA consortium.
AB - BACKGROUND: We previously showed that the BRCA1 variant c.5096G>A p.Arg1699Gln
(R1699Q) was associated with an intermediate risk of breast cancer (BC) and
ovarian cancer (OC). This study aimed to assess these cancer risks for R1699Q
carriers in a larger cohort, including follow-up of previously studied families,
to further define cancer risks and to propose adjusted clinical management of
female BRCA1*R1699Q carriers. METHODS: Data were collected from 129 BRCA1*R1699Q
families ascertained internationally by ENIGMA (Evidence-based Network for the
Interpretation of Germline Mutant Alleles) consortium members. A modified
segregation analysis was used to calculate BC and OC risks. Relative risks were
calculated under both monogenic model and major gene plus polygenic model
assumptions. RESULTS: In this cohort the cumulative risk of BC and OC by age 70
years was 20% and 6%, respectively. The relative risk for developing cancer was
higher when using a model that included the effects of both the R1699Q variant
and a residual polygenic component compared with monogenic model (for BC 3.67 vs
2.83, and for OC 6.41 vs 5.83). CONCLUSION: Our results confirm that BRCA1*R1699Q
confers an intermediate risk for BC and OC. Breast surveillance for female
carriers based on mammogram annually from age 40 is advised. Bilateral salpingo
oophorectomy should be considered based on family history.
PMID- 28490615
TI - Contemporary natural history of bicuspid aortic valve disease: a systematic
review.
AB - We performed a systematic review of the current state of the literature regarding
the natural history and outcomes of bicuspid aortic valve (BAV). PubMed and the
reference lists of the included articles were searched for relevant studies
reporting on longitudinal follow-up of BAV cohorts (mean follow-up >=2 years).
Studies limited to patients undergoing surgical interventions were excluded. 13
studies (11 502 patients with 2-16 years of follow-up) met the inclusion
criteria. There was a bimodal age distribution (30-40 vs >=50 years), with a 3:1
male to female ratio. Complications included moderate to severe aortic
regurgitation (prevalence 13%-30%), moderate to severe aortic stenosis (12%-37%),
infective endocarditis (2%-5%) and aortic dilatation (20%-40%). Aortic dissection
or rupture was rare, occurring in 38 patients (0.4%, 27/6446 in native BAV and
11/2232 in post). With current aggressive surveillance and prophylactic surgical
interventions, survival in three out of four studies was similar to that of a
matched general population. In this systematic review, valvular dysfunction
warranting surgical intervention in patients with BAV were common, aortic
dissection was rare and, with the current management approach, survival was
similar to that of the general population.
PMID- 28490616
TI - Integrated care in atrial fibrillation: a systematic review and meta-analysis.
AB - OBJECTIVE: Atrial fibrillation (AF) is an emerging global epidemic associated
with significant morbidity and mortality. Whilst other chronic cardiovascular
conditions have demonstrated enhanced patient outcomes from coordinated systems
of care, the use of this approach in AF is a comparatively new concept. Recent
evidence has suggested that the integrated care approach may be of benefit in the
AF population, yet has not been widely implemented in routine clinical practice.
We sought to undertake a systematic review and meta-analysis to evaluate the
impact of integrated care approaches to care delivery in the AF population on
outcomes including mortality, hospitalisations, emergency department visits,
cerebrovascular events and patient-reported outcomes. METHODS: PubMed, Embase and
CINAHL databases were searched until February 2016 to identify papers addressing
the impact of integrated care in the AF population. Three studies, with a total
study population of 1383, were identified that compared integrated care
approaches with usual care in AF populations. RESULTS: Use of this approach was
associated with a reduction in all-cause mortality (OR 0.51, 95% CI 0.32 to 0.80,
p=0.003) and cardiovascular hospitalisations (OR 0.58, 95% CI 0.44 to 0.77,
p=0.0002) but did not significantly impact on AF-related hospitalisations (OR
0.82, 95% CI 0.56 to 1.19, p=0.29) or cerebrovascular events (OR 1.00, 95% CI
0.48 to 2.09, p=1.00). CONCLUSIONS: The use of the integrated care approach in AF
is associated with reduced cardiovascular hospitalisations and all-cause
mortality. Further research is needed to identify optimal settings, methods and
components of delivering integrated care to the burgeoning AF population.
PMID- 28490617
TI - Systemic inflammation as a novel QT-prolonging risk factor in patients with
torsades de pointes.
AB - OBJECTIVE: Increasing evidence indicates systemic inflammation as a new potential
cause of acquired long QT syndrome (LQTS), via cytokine-mediated changes in
cardiomyocyte ion channels. Torsade de pointes (TdP) is a life-threatening
polymorphic ventricular tachycardia occurring in patients with LQTS, usually when
multiple QT-prolonging factors are simultaneously present. Since classical risk
factors cannot fully explain TdP events in a number of patients, we hypothesised
that systemic inflammation may represent a currently overlooked risk factor
contributing to TdP development in the general population. METHODS: Forty
consecutive patients who experienced TdP (TdP cohort) were consecutively enrolled
and circulating levels of C-reactive protein (CRP) and proinflammatory cytokines
(interleukin-6 (IL-6), tumour necrosis factor alpha (TNFalpha), interleukin-1 (IL
1)) were compared with patients with active rheumatoid arthritis (RA),
comorbidity or healthy controls. An additional 46 patients with different
inflammatory conditions (acute infections, n=31; immune-mediated diseases, n=12;
others, n=3) and elevated CRP (inflammatory cohort) were prospectively enrolled,
and corrected QT (QTc) and cytokine levels were measured during active disease
and after a CRP decrease of >75% subsequent to therapy. RESULTS: In the TdP
cohort, 80% of patients showed elevated CRP levels (median: ~3 mg/dL), with a
definite inflammatory disease identifiable in 18/40 cases (acute infections,
n=12; immune-mediated diseases, n=5; others, n=1). In these subjects, IL-6, but
not TNFalpha and IL-1, was ~15-20 times higher than in controls, and comparable
to RA patients. In the inflammatory cohort, where QTc prolongation was common
(mean values: 456.6+/-30.9 ms), CRP reduction was associated with IL-6 level
decrease and significant QTc shortening (-22.3 ms). CONCLUSION: The data are
first to show that systemic inflammation via elevated IL-6 levels may represent a
novel QT-prolonging risk factor contributing to TdP occurrence in the presence of
other classical risk factors. If confirmed, this could open new avenues in
antiarrhythmic therapy.
PMID- 28490618
TI - 21-year-old with exertional dyspnoea.
PMID- 28490620
TI - Physical activity evaluation in children with congenital heart disease.
AB - Significant advances in the management of children with congenital heart disease
(CHD) have resulted in marked improvements in survival and life expectancy. Thus,
there is an increased emphasis on promoting physical activity to optimise healthy
development and long-term cardiovascular health. Evaluation of physical activity
levels as part of ongoing clinical care is recommended to facilitate physical
activity counselling and/or exercise prescription. Physical activity is a complex
health behaviour that is challenging to evaluate. We provide an overview of
techniques for measuring physical activity in children with CHD with a focus on
how to do this in the clinical context. Accelerometers are devices that
objectively assess intensity and duration of physical activity under free living
conditions. They enable evaluation against physical activity guidelines, but are
costly and require advanced technical expertise. Pedometers are a simple-to-use
and cost-effective alternative, but an outcome metric of daily step count limits
classification against guidelines. Commercial wearable activity trackers offer an
appealing user experience and can provide valid estimates in children.
Furthermore, activity trackers enable remote monitoring of physical activity
levels, which may facilitate exercise prescription and activity counselling.
Questionnaires are the most cost-effective and time-effective method, but recall
error in younger children is a consideration. Routine exercise testing in
children with CHD provides important insight into functional status but should
not be viewed as a proxy measure of habitual physical activity. Understanding the
spectrum and role of physical activity measurement tools is important for
clinicians focused on optimising cardiovascular health in children with CHD.
PMID- 28490619
TI - Capacity for diagnosis and treatment of heart failure in sub-Saharan Africa.
AB - OBJECTIVE: Heart failure is a major cause of disease burden in sub-Saharan Africa
(SSA). There is an urgent need for better strategies for heart failure management
in this region. However, there is little information on the capacity to diagnose
and treat heart failure in SSA. We aim to provide a better understanding of the
capacity to diagnose and treat heart failure in Kenya and Uganda to inform policy
planning and interventions. METHODS: We analysed data from a nationally
representative survey of health facilities in Kenya and Uganda (197 health
facilities in Uganda and 143 in Kenya). We report on the availability of cardiac
diagnostic technologies and select medications for heart failure (beta-blockers,
ACE inhibitors and furosemide). Facility-level data were analysed by country and
platform type (hospital vs ambulatory facilities). RESULTS: Functional and
staffed radiography, ultrasound and ECG were available in less than half of
hospitals in Kenya and Uganda combined. Of the hospitals surveyed, 49% of Kenyan
and 77% of Ugandan hospitals reported availability of the heart failure
medication package. ACE inhibitors were only available in 51% of Kenyan and 79%
of Ugandan hospitals. Almost one-third of the hospitals in each country had a
stock-out of at least one of the medication classes in the prior quarter.
CONCLUSIONS: Few facilities in Kenya and Uganda were prepared to diagnose and
manage heart failure. Medication shortages and stock-outs were common. Our
findings call for increased investment in cardiac care to reduce the growing
burden of heart failure.
PMID- 28490621
TI - Plasma 7-ketocholesterol levels and the risk of incident cardiovascular events.
AB - OBJECTIVE: 7-Ketocholesterol (7-KC), a major oxidation product of cholesterol, is
found in human atherosclerotic plaque and more atherogenic than cholesterol in
animal models. This study was designed to investigate the association of plasma 7
KC level with the incident cardiovascular disease (CVD) events in general
population. METHODS: We measured plasma 7-KC concentrations at baseline in 1944
participants free from CVD in a community-based cohort study. The primary
endpoint was incident of a major adverse cardiovascular event. A Cox proportional
hazards model was used to calculate the HRs with 95% CI. RESULTS: A total of 101
incident CVD events were recorded during the 5.2 year median follow-up. The
baseline plasma 7-KC levels were associated with a higher risk of incident CVD
events; compared with quartile 1, participants in quartile 4 had an unadjusted HR
of 2.38 (2.03-2.85, p<0.001) and an adjusted HR of 1.70 (1.45-1.91, p=0.004)
after adjusting for traditional risk factors. Plasma 7-KC levels improved all of
the metrics of discrimination and reclassification when added to the intima-media
thickness (C-statistic: p=0.002; net reclassification improvement (NRI): p<0.001;
integrated discrimination improvement (IDI): p<0.001), family history of
myocardial infarction (C-statistic: p=0.011; NRI: p=0.004; IDI: p=0.003) and
elevated high-sensitivity C reactive protein (C-statistic: p=0.008; NRI: p=0.015;
IDI: p=0.009). CONCLUSIONS: Elevated plasma 7-KC levels are associated with the
incident CVD events in a population-based cohort. Further studies are needed to
confirm this observation.
PMID- 28490622
TI - Mutualistic strategies minimize coextinction in plant-disperser networks.
AB - The global decline of mutualists such as pollinators and seed dispersers may
cause negative direct and indirect impacts on biodiversity. Mutualistic network
models used to understand the stability of mutualistic systems indicate that
species with low partner diversity are most vulnerable to coextinction following
mutualism disruption. However, existing models have not considered how species
vary in their dependence on mutualistic interactions for reproduction or
survival, overlooking the potential influence of this variation on species'
coextinction vulnerability and on network stability. Using global databases and
field experiments focused on the seed dispersal mutualism, we found that plants
and animals that depend heavily on mutualistic interactions have higher partner
diversity. Under simulated network disruption, this empirical relationship
strongly reduced coextinction because the species most likely to lose mutualists
depend least on their mutualists. The pattern also reduced the importance of
network structure for stability; nested network structure had little effect on
coextinction after simulations incorporated the empirically derived relationship
between partner diversity and mutualistic dependence. Our results highlight a
previously unknown source of stability in mutualistic networks and suggest that
differences among species in their mutualistic strategy, rather than network
structure, primarily accounts for stability in mutualistic communities.
PMID- 28490623
TI - Genetics-based interactions of foundation species affect community diversity,
stability and network structure.
AB - We examined the hypothesis that genetics-based interactions between strongly
interacting foundation species, the tree Populus angustifolia and the aphid
Pemphigus betae, affect arthropod community diversity, stability and species
interaction networks of which little is known. In a 2-year experimental
manipulation of the tree and its aphid herbivore four major findings emerged: (i)
the interactions of these two species determined the composition of an arthropod
community of 139 species; (ii) both tree genotype and aphid presence
significantly predicted community diversity; (iii) the presence of aphids on
genetically susceptible trees increased the stability of arthropod communities
across years; and (iv) the experimental removal of aphids affected community
network structure (network degree, modularity and tree genotype contribution to
modularity). These findings demonstrate that the interactions of foundation
species are genetically based, which in turn significantly contributes to
community diversity, stability and species interaction networks. These
experiments provide an important step in understanding the evolution of Darwin's
'entangled bank', a metaphor that characterizes the complexity and
interconnectedness of communities in the wild.
PMID- 28490624
TI - Removal of an apex predator initiates a trophic cascade that extends from
herbivores to vegetation and the soil nutrient pool.
AB - It is widely assumed that organisms at low trophic levels, particularly microbes
and plants, are essential to basic services in ecosystems, such as nutrient
cycling. In theory, apex predators' effects on ecosystems could extend to
nutrient cycling and the soil nutrient pool by influencing the intensity and
spatial organization of herbivory. Here, we take advantage of a long-term
manipulation of dingo abundance across Australia's dingo-proof fence in the
Strzelecki Desert to investigate the effects that removal of an apex predator has
on herbivore abundance, vegetation and the soil nutrient pool. Results showed
that kangaroos were more abundant where dingoes were rare, and effects of
kangaroo exclusion on vegetation, and total carbon, total nitrogen and available
phosphorus in the soil were marked where dingoes were rare, but negligible where
dingoes were common. By showing that a trophic cascade resulting from an apex
predator's lethal effects on herbivores extends to the soil nutrient pool, we
demonstrate a hitherto unappreciated pathway via which predators can influence
nutrient dynamics. A key implication of our study is the vast spatial scale
across which apex predators' effects on herbivore populations operate and, in
turn, effects on the soil nutrient pool and ecosystem productivity could become
manifest.
PMID- 28490625
TI - Nonlinear trade-offs allow the cooperation game to evolve from Prisoner's Dilemma
to Snowdrift.
AB - The existence of cooperation, or the production of public goods, is an
evolutionary problem. Cooperation is not favoured because the Prisoner's Dilemma
(PD) game drives cooperators to extinction. We have re-analysed this problem by
using RNA viruses to motivate a model for the evolution of cooperation. Gene
products are the public goods and group size is the number of virions co
infecting the same host cell. Our results show that if the trade-off between
replication and production of gene products is linear, PD is observed. However,
if the trade-off is nonlinear, the viruses evolve into separate lineages of ultra
defectors and ultra-cooperators as group size is increased. The nonlinearity was
justified by the existence of real viral ultra-defectors, known as defective
interfering particles, which gain a nonlinear advantage by being smaller. The
evolution of ultra-defectors and ultra-cooperators creates the Snowdrift game,
which promotes high-level production of public goods.
PMID- 28490626
TI - Minimal variation in eutherian brain growth rates during fetal neurogenesis.
AB - A central question in the evolution of brain development is whether species
differ in rates of brain growth during fetal neurogenesis. Studies of neonatal
data have found allometric evidence for brain growth rate differences according
to physiological variables such as relative metabolism and placental
invasiveness, but these findings have not been tested against fetal data
directly. Here, we measure rates of exponential brain growth acceleration in 10
eutherian mammals, two marsupials, and two birds. Eutherian brain acceleration
exhibits minimal variation relative to body and visceral organ growth, varies
independently of correlated growth patterns in other organs, and is unrelated to
proposed physiological constraints such as metabolic rate or placental
invasiveness. Brain growth rates in two birds overlap with eutherian variation,
while marsupial brain growth is exceptionally slow. Peak brain growth velocity is
linked in time with forebrain myelination and eye opening, reliably separates
altricial species born before it from precocial species born afterwards, and is
an excellent predictor of adult brain size (r2 = 0.98). Species with faster body
growth exhibit larger relative brain size in early ontogeny, while brain growth
is unrelated to allometric measures. These findings indicate a surprising
conservation of brain growth rates during fetal neurogenesis in eutherian
mammals, clarify sources of variation in neonatal brain size, and suggest that
slow body growth rates cause species to be more encephalized at birth.
PMID- 28490627
TI - Concerted and mosaic evolution of functional modules in songbird brains.
AB - Vertebrate brains differ in overall size, composition and functional capacities,
but the evolutionary processes linking these traits are unclear. Two leading
models offer opposing views: the concerted model ascribes major dimensions of
covariation in brain structures to developmental events, whereas the mosaic model
relates divergent structures to functional capabilities. The models are often
cast as incompatible, but they must be unified to explain how adaptive changes in
brain structure arise from pre-existing architectures and developmental
mechanisms. Here we show that variation in the sizes of discrete neural systems
in songbirds, a species-rich group exhibiting diverse behavioural and ecological
specializations, supports major elements of both models. In accordance with the
concerted model, most variation in nucleus volumes is shared across functional
domains and allometry is related to developmental sequence. Per the mosaic model,
residual variation in nucleus volumes is correlated within functional systems and
predicts specific behavioural capabilities. These comparisons indicate that
oscine brains evolved primarily as a coordinated whole but also experienced
significant, independent modifications to dedicated systems from specific
selection pressures. Finally, patterns of covariation between species and brain
areas hint at underlying developmental mechanisms.
PMID- 28490629
TI - Pharmacological targeting of RAD6 enzyme-mediated translesion synthesis overcomes
resistance to platinum-based drugs.
AB - Platinum drug-induced cross-link repair requires the concerted activities of
translesion synthesis (TLS), Fanconi anemia (FA), and homologous recombination
repair pathways. The E2 ubiquitin-conjugating enzyme RAD6 is essential for TLS.
Here, we show that RAD6 plays a universal role in platinum-based drug tolerance.
Using a novel RAD6-selective small-molecule inhibitor (SMI#9) targeting the RAD6
catalytic site, we demonstrate that SMI#9 potentiates the sensitivities of cancer
cells with innate or acquired cisplatin or oxaliplatin resistance. 5
Iododeoxyuridine/5-chlorodeoxyuridine pulse-labeling experiments showed that RAD6
is necessary for overcoming cisplatin-induced replication fork stalling, as
replication-restart was impaired in both SMI#9-pretreated and RAD6B-silenced
cells. Consistent with the role of RAD6/TLS in late-S phase, SMI#9-induced DNA
replication inhibition occurred preferentially in mid/late-S phase. The
compromised DNA repair and chemosensitization induced by SMI#9 or RAD6B depletion
were associated with decreased platinum drug-induced proliferating cell nuclear
antigen (PCNA) and FANCD2 monoubiquitinations (surrogate markers of TLS and FA
pathway activation, respectively) and with attenuated FANCD2, RAD6, gammaH2AX,
and POL eta foci formation and cisplatin-adduct removal. SMI#9 pretreatment
synergistically increased cisplatin inhibition of MDA-MB-231 triple-negative
breast cancer cell proliferation and tumor growth. Using an isogenic HCT116 colon
cancer model of oxaliplatin resistance, we further show that gammaH2AX and
monoubiquitinated PCNA and FANCD2 are constitutively up-regulated in oxaliplatin
resistant HCT116 (HCT116-OxR) cells and that gammaH2AX, PCNA, and FANCD2
monoubiquitinations are induced by oxaliplatin in parental HCT116 cells. SMI#9
pretreatment sensitized HCT116-OxR cells to oxaliplatin. These data deepen
insights into the vital role of RAD6/TLS in platinum drug tolerance and reveal
clinical benefits of targeting RAD6 with SMI#9 for managing chemoresistant
cancers.
PMID- 28490630
TI - Understanding phospholipid function: Why are there so many lipids?
AB - In the 1970s, phospholipids were still considered mere building blocks of the
membrane lipid bilayer, but the subsequent realization that phospholipids could
also serve as second messengers brought new interest to the field. My own passion
for the unique amphipathic properties of lipids led me to seek other, non
signaling functions for phospholipids, particularly in their interactions with
membrane proteins. This seemed to be the last frontier in protein chemistry and
enzymology to be conquered. I was fortunate to find my way to Eugene Kennedy's
laboratory, where both membrane proteins and phospholipids were the foci of
study, thus providing a jumping-off point for advancing our fundamental
understanding of lipid synthesis, membrane protein biosynthesis, phospholipid and
membrane protein trafficking, and the cellular roles of phospholipids. After
purifying and characterizing enzymes of phospholipid biosynthesis in Escherichia
coli and cloning of several of the genes encoding these enzymes in E. coli and
Saccharomyces cerevisiae, I was in a position to alter phospholipid composition
in a systematic manner during the cell cycle in these microorganisms. My group
was able to establish, contrary to common assumption (derived from the fact that
membrane proteins retain activity in detergent extracts) that phospholipid
environment is a strong determining factor in the function of membrane proteins.
We showed that molecular genetic alterations in membrane lipid composition result
in many phenotypes, and uncovered direct lipid-protein interactions that govern
dynamic structural and functional properties of membrane proteins. Here I present
my personal "reflections" on how our understanding of phospholipid functions has
evolved.
PMID- 28490632
TI - Cell death-inducing DNA fragmentation factor A-like effector A and fat-specific
protein 27beta coordinately control lipid droplet size in brown adipocytes.
AB - Adipose tissue stores neutral lipids and is a major metabolic organ involved in
regulating whole-body energy homeostasis. Triacylglycerol is stored as unilocular
large lipid droplets (LDs) in white adipocytes and as multilocular small LDs in
brown adipocytes. Proteins of the cell death-inducing DNA fragmentation factor A
like effector (Cide) family include CideA, CideB, and fat-specific protein of 27
(FSP27). Of these, FSP27 has been shown to play a crucial role in the formation
of unilocular large LDs in white adipocytes. However, the mechanisms by which
brown adipocytes store small and multilocular LDs remain unclear. An FSP27
isoform, FSP27beta, was recently identified. We herein report that CideA and
FSP27beta are mainly expressed in brown adipose tissue and that FSP27beta
overexpression inhibits CideA-induced LD enlargements in a dose-dependent manner
in COS cells. Furthermore, RNAi-mediated FSP27beta depletion resulted in enlarged
LDs in HB2 adipocytes, which possess the characteristics of brown adipocytes.
Brown adipocytes in FSP27-knock-out mice that express CideA, but not FSP27beta,
had larger and fewer LDs. Moreover, we confirmed that FSP27beta and CideA form a
complex in brown adipose tissue. Our results suggest that FSP27beta negatively
regulates CideA-promoted enlargement of LD size in brown adipocytes. FSP27beta
appears to be responsible for the formation of small and multilocular LDs in
brown adipose tissue, a morphology facilitating free fatty acid transport to
mitochondria adjacent to LDs for oxidation in brown adipocytes.
PMID- 28490631
TI - A split-luciferase complementation, real-time reporting assay enables monitoring
of the disease-associated transmembrane protein TREM2 in live cells.
AB - Triggering receptor expressed on myeloid cells 2 (TREM2) is a single
transmembrane molecule uniquely expressed in microglia. TREM2 mutations are
genetically linked to Nasu-Hakola disease and associated with multiple
neurodegenerative disorders, including Alzheimer's disease. TREM2 may regulate
microglial inflammation and phagocytosis through coupling to the adaptor protein
TYRO protein-tyrosine kinase-binding protein (TYROBP). However, there is no
functional system for monitoring this protein-protein interaction. We developed a
luciferase-based modality for real-time monitoring of TREM2-TYROBP coupling in
live cells that utilizes split-luciferase complementation technology based on
TREM2 and TYROBP fusion to the C- or N-terminal portion of the Renilla luciferase
gene. Transient transfection of human embryonic kidney 293 cells with this
reporter vector increased luciferase activity upon stimulation with an anti-TREM2
antibody, which induces their homodimerization. This was confirmed by ELISA-based
analysis of the TREM2-TYROBP interaction. Antibody-mediated TREM2 stimulation
enhanced spleen tyrosine kinase (SYK) activity and uptake of Staphylococcus
aureus in microglial cell line BV-2 in a kinase-dependent manner. Interestingly,
the TREM2 T66M mutation significantly enhanced luciferase activity without
stimulation, indicating constitutive coupling to TYROBP. Finally, flow cytometry
analyses indicated significantly lower surface expression of T66M TREM2 variant
than wild type or other TREM2 variants. These results demonstrate that our TREM2
reporter vector is a novel tool for monitoring the TREM2-TYROBP interaction in
real time.
PMID- 28490633
TI - Single-particle electron microscopy structure of UDP-glucose:glycoprotein
glucosyltransferase suggests a selectivity mechanism for misfolded proteins.
AB - The enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) mediates quality
control of glycoproteins in the endoplasmic reticulum by attaching glucose to N
linked glycan of misfolded proteins. As a sensor, UGGT ensures that misfolded
proteins are recognized by the lectin chaperones and do not leave the secretory
pathway. The structure of UGGT and the mechanism of its selectivity for misfolded
proteins have been unknown for 25 years. Here, we used negative-stain electron
microscopy and small-angle X-ray scattering to determine the structure of UGGT
from Drosophila melanogaster at 18-A resolution. Three-dimensional
reconstructions revealed a cage-like structure with a large central cavity.
Particle classification revealed flexibility that precluded determination of a
high-resolution structure. Introduction of biotinylation sites into a fungal UGGT
expressed in Escherichia coli allowed identification of the catalytic and first
thioredoxin-like domains. We also used hydrogen-deuterium exchange mass
spectrometry to map the binding site of an accessory protein, Sep15, to the first
thioredoxin-like domain. The UGGT structural features identified suggest that the
central cavity contains the catalytic site and is lined with hydrophobic
surfaces. This enhances the binding of misfolded substrates with exposed
hydrophobic residues and excludes folded proteins with hydrophilic surfaces. In
conclusion, we have determined the UGGT structure, which enabled us to develop a
plausible functional model of the mechanism for UGGT's selectivity for misfolded
glycoproteins.
PMID- 28490634
TI - Inflammatory cytokines down-regulate the barrier-protective prostasin-matriptase
proteolytic cascade early in experimental colitis.
AB - Compromised gastrointestinal barrier function is strongly associated with the
progressive and destructive pathologies of the two main forms of irritable bowel
disease (IBD), ulcerative colitis (UC), and Crohn's disease (CD). Matriptase is a
membrane-anchored serine protease encoded by suppression of tumorigenicity-14
(ST14) gene, which is critical for epithelial barrier development and
homeostasis. Matriptase barrier-protective activity is linked with the
glycosylphosphatidylinositol (GPI)-anchored serine protease prostasin, which is a
co-factor for matriptase zymogen activation. Here we show that mRNA and protein
expression of both matriptase and prostasin are rapidly down-regulated in the
initiating inflammatory phases of dextran sulfate sodium (DSS)-induced
experimental colitis in mice, and, significantly, the loss of these proteases
precedes the appearance of clinical symptoms, suggesting their loss may
contribute to disease susceptibility. We used heterozygous St14 hypomorphic mice
expressing a promoter-linked beta-gal reporter to show that inflammatory colitis
suppresses the activity of the St14 gene promoter. Studies in colonic T84 cell
monolayers revealed that barrier disruption by the colitis-associated Th2-type
cytokines, IL-4 and IL-13, down-regulates matriptase as well as prostasin through
phosphorylation of the transcriptional regulator STAT6 and that inhibition of
STAT6 with suberoylanilide hydroxamic acid (SAHA) restores protease expression
and reverses cytokine-induced barrier dysfunction. Both matriptase and prostasin
are significantly down-regulated in colonic tissues from human subjects with
active ulcerative colitis or Crohn's disease, implicating the loss of this
barrier-protective protease pathway in the pathogenesis of irritable bowel
disease.
PMID- 28490635
TI - The FOXO transcription factor controls insect growth and development by
regulating juvenile hormone degradation in the silkworm, Bombyx mori.
AB - Forkhead box O (FOXO) functions as the terminal transcription factor of the
insulin signaling pathway and regulates multiple physiological processes in many
organisms, including lifespan in insects. However, how FOXO interacts with
hormone signaling to modulate insect growth and development is largely unknown.
Here, using the transgene-based CRISPR/Cas9 system, we generated and
characterized mutants of the silkworm Bombyx mori FOXO (BmFOXO) to elucidate its
physiological functions during development of this lepidopteran insect. The
BmFOXO mutant (FOXO-M) exhibited growth delays from the first larval stage and
showed precocious metamorphosis, pupating at the end of the fourth instar
(trimolter) rather than at the end of the fifth instar as in the wild-type (WT)
animals. However, different from previous reports on precocious metamorphosis
caused by juvenile hormone (JH) deficiency in silkworm mutants, the total
developmental time of the larval period in the FOXO-M was comparable with that of
the WT. Exogenous application of 20-hydroxyecdysone (20E) or of the JH analog
rescued the trimolter phenotype. RNA-seq and gene expression analyses indicated
that genes involved in JH degradation but not in JH biosynthesis were up
regulated in the FOXO-M compared with the WT animals. Moreover, we identified
several FOXO-binding sites in the promoter of genes coding for JH-degradation
enzymes. These results suggest that FOXO regulates JH degradation rather than its
biosynthesis, which further modulates hormone homeostasis to control growth and
development in B. mori In conclusion, we have uncovered a pivotal role for FOXO
in regulating JH signaling to control insect development.
PMID- 28490636
TI - The Cox1 C-terminal domain is a central regulator of cytochrome c oxidase
biogenesis in yeast mitochondria.
AB - Cytochrome c oxidase (CcO) is the last electron acceptor in the respiratory
chain. The CcO core is formed by mitochondrial DNA-encoded Cox1, Cox2, and Cox3
subunits. Cox1 synthesis is highly regulated; for example, if CcO assembly is
blocked, Cox1 synthesis decreases. Mss51 activates translation of COX1 mRNA and
interacts with Cox1 protein in high-molecular-weight complexes (COA complexes) to
form the Cox1 intermediary assembly module. Thus, Mss51 coordinates both Cox1
synthesis and assembly. We previously reported that the last 15 residues of the
Cox1 C terminus regulate Cox1 synthesis by modulating an interaction of Mss51
with Cox14, another component of the COA complexes. Here, using site-directed
mutagenesis of the mitochondrial COX1 gene from Saccharomyces cerevisiae, we
demonstrate that mutations P521A/P522A and V524E disrupt the regulatory role of
the Cox1 C terminus. These mutations, as well as C terminus deletion
(Cox1DeltaC15), reduced binding of Mss51 and Cox14 to COA complexes. Mss51 was
enriched in a translationally active form that maintains full Cox1 synthesis even
if CcO assembly is blocked in these mutants. Moreover, Cox1DeltaC15, but not Cox1
P521A/P522A and Cox1-V524E, promoted formation of aberrant supercomplexes in CcO
assembly mutants lacking Cox2 or Cox4 subunits. The aberrant supercomplex
formation depended on the presence of cytochrome b and Cox3, supporting the idea
that supercomplex assembly factors associate with Cox3 and demonstrating that
supercomplexes can be formed even if CcO is inactive and not fully assembled. Our
results indicate that the Cox1 C-terminal end is a key regulator of CcO
biogenesis and that it is important for supercomplex formation/stability.
PMID- 28490637
TI - Does Semantic Congruency Accelerate Episodic Encoding, or Increase Semantic
Elaboration?
PMID- 28490638
TI - Immunomodulation via Toll-like Receptor 9: An Adjunct Therapy Strategy against
Alzheimer's Disease?
PMID- 28490640
TI - Transcribing the connectome: roles for transcription factors and chromatin
regulators in activity-dependent synapse development.
AB - The wiring of synaptic connections in the developing mammalian brain is shaped by
both intrinsic and extrinsic signals. One point where these regulatory pathways
converge is via the sensory experience-dependent regulation of new gene
transcription. Recent studies have elucidated a number of molecular mechanisms
that allow nuclear transcription factors and chromatin regulatory proteins to
encode aspects of specificity in experience-dependent synapse development. Here
we review the evidence for the transcriptional mechanisms that sculpt activity
dependent aspects of synaptic connectivity during postnatal development and
discuss how disruption of these processes is associated with aberrant brain
development in autism and intellectual disability.
PMID- 28490641
TI - Fetal alcohol exposure reduces responsiveness of taste nerves and trigeminal
chemosensory neurons to ethanol and its flavor components.
AB - Fetal alcohol exposure (FAE) leads to increased intake of ethanol in adolescent
rats and humans. We asked whether these behavioral changes may be mediated in
part by changes in responsiveness of the peripheral taste and oral trigeminal
systems. We exposed the experimental rats to ethanol in utero by administering
ethanol to dams through a liquid diet; we exposed the control rats to an
isocaloric and isonutritive liquid diet. To assess taste responsiveness, we
recorded responses of the chorda tympani (CT) and glossopharyngeal (GL) nerves to
lingual stimulation with ethanol, quinine, sucrose, and NaCl. To assess
trigeminal responsiveness, we measured changes in calcium levels of isolated
trigeminal ganglion (TG) neurons during stimulation with ethanol, capsaicin,
mustard oil, and KCl. Compared with adolescent control rats, the adolescent
experimental rats exhibited diminished CT nerve responses to ethanol, quinine,
and sucrose and GL nerve responses to quinine and sucrose. The reductions in
taste responsiveness persisted into adulthood for quinine but not for any of the
other stimuli. Adolescent experimental rats also exhibited reduced TG neuron
responses to ethanol, capsaicin, and mustard oil. The lack of change in
responsiveness of the taste nerves to NaCl and the TG neurons to KCl indicates
that FAE altered only a subset of the response pathways within each chemosensory
system. We propose that FAE reprograms development of the peripheral taste and
trigeminal systems in ways that reduce their responsiveness to ethanol and
surrogates for its pleasant (i.e., sweet) and unpleasant (i.e., bitterness, oral
burning) flavor attributes.NEW & NOTEWORTHY Pregnant mothers are advised to avoid
alcohol. This is because even small amounts of alcohol can alter fetal brain
development and increase the risk of adolescent alcohol abuse. We asked how fetal
alcohol exposure (FAE) produces the latter effect in adolescent rats by measuring
responsiveness of taste nerves and trigeminal chemosensory neurons. We found that
FAE substantially reduced taste and trigeminal responsiveness to ethanol and its
flavor components.
PMID- 28490642
TI - Split-arm swinging: the effect of arm swinging manipulation on interlimb
coordination during walking.
AB - Human locomotion is defined by bilateral coordination of gait (BCG) and shared
features with the fore-hindlimb coordination of quadrupeds. The objective of the
present study is to explore the influence of arm swinging (AS) on BCG. Sixteen
young, healthy individuals (eight women; eight right motor-dominant, eight left
motor dominant) participated. Participants performed 10 walking trials (2 min).
In each of the trials AS was unilaterally manipulated (e.g., arm restriction,
weight on the wrist), bilaterally manipulated, or not manipulated. The order of
trials was random. Walking trials were performed on a treadmill. Gait kinematics
were recorded by a motion capture system. Using feedback-controlled belt speed
allowed the participants to walk at a self-determined gait speed. Effects of the
manipulations were assessed by AS amplitudes and the phase coordination index
(PCI), which quantifies the left-right anti-phased stepping pattern. Most of the
AS manipulations caused an increase in PCI values (i.e., reduced lower limb
coordination). Unilateral AS manipulation had a reciprocal effect on the AS
amplitude of the other arm such that, for example, over-swinging of the right arm
led to a decrease in the AS amplitude of the left arm. Side of motor dominance
was not found to have a significant impact on PCI and AS amplitude. The present
findings suggest that lower limb BCG is markedly influenced by the rhythmic AS
during walking. It may thus be important for gait rehabilitation programs
targeting BCG to take AS into account.NEW & NOTEWORTHY Control mechanisms for
four-limb coordination in human locomotion are not fully known. To study the
influence of arm swinging (AS) on bilateral coordination of the lower limbs
during walking, we introduced a split-AS paradigm in young, healthy adults. AS
manipulations caused deterioration in the anti-phased stepping pattern and
impacted the AS amplitudes for the contralateral arm, suggesting that lower limb
coordination is markedly influenced by the rhythmic AS during walking.
PMID- 28490643
TI - Predicting the response of striatal spiny neurons to sinusoidal input.
AB - Spike-timing effects of small-amplitude sinusoidal currents were measured in
mouse striatal spiny neurons firing repetitively. Spike-timing reliability varied
with the stimulus frequency. For frequencies near the cell's firing rate, the
cells altered firing rate to match the stimulus and became phase locked to it.
The stimulus phase of firing during lock depended on the stimulus frequency
relative to the cell's unperturbed firing rate. Interspike intervals during
sinusoidal stimulation were predicted using an iterative map constructed from the
cells' phase-resetting curve. Variability of interspike intervals was reduced by
stimulation at all frequencies higher than about half the cell's unperturbed
rate, and interspike intervals were accurately predicted by the map. Long
sequences of spike times were predicted by iterating on the map. The accuracy of
that prediction varied with frequency. Spike time predictability was highest near
and during phase lock. The map predicted the phase of firing on the input and its
dependence on stimulus frequency. Prediction errors, when they occurred, were of
two kinds: unpredicted variation in interspike interval from intrinsic cell noise
and accumulation of prediction errors from previous interspike intervals. Each
type of prediction error arose from a different mechanism, and their impact was
also predicted from the phase model. When two oscillatory input currents were
presented simultaneously, striatal neurons responded selectively to only one of
them, the one closest in frequency to the cell's unperturbed firing rate. Their
spike times encoded the frequency and phase of that single oscillatory input.NEW
& NOTEWORTHY During repetitive firing, the timing of action potentials is
determined by the interaction between the input and voltage-sensitive currents
throughout the interspike interval. This interaction is encapsulated in the
neuron's phase-resetting curve. The phase-resetting curve predicted spike timing
to small sinusoidal currents over a wide range of stimulus frequencies. Firing
patterns were most sensitive to oscillatory components near the cell's own firing
rate, even in the presence of noise and other inputs.
PMID- 28490645
TI - Evidence of adaptations of locomotor neural drive in response to enhanced
intermuscular connectivity between the triceps surae muscles of the rat.
AB - The aims of this study were to investigate changes 1) in the coordination of
activation of the triceps surae muscle group, and 2) in muscle belly length of
soleus (SO) and lateral gastrocnemius (LG) during locomotion (trotting) in
response to increased stiffness of intermuscular connective tissues in the rat.
We measured muscle activation and muscle belly lengths, as well as hindlimb
kinematics, before and after an artificial enhancement of the connectivity
between SO and LG muscles obtained by implanting a tissue-integrating surgical
mesh at the muscles' interface. We found that SO muscle activation decreased to
62%, while activation of LG and medial gastrocnemius muscles increased to 134 and
125%, respectively, compared with the levels measured preintervention. Although
secondary additional or amplified activation bursts were observed with enhanced
connectivity, the primary pattern of activation over the stride and the burst
duration were not affected by the intervention. Similar muscle length changes
after manipulation were observed, suggesting that length feedback from spindle
receptors within SO and LG was not affected by the connectivity enhancement. We
conclude that peripheral mechanical constraints given by morphological
(re)organization of connective tissues linking synergists are taken into account
by the central nervous system. The observed shift in activity toward the
gastrocnemius muscles after the intervention suggests that these larger muscles
are preferentially recruited when the soleus has a similar mechanical
disadvantage in that it produces an unwanted flexion moment around the knee.NEW &
NOTEWORTHY Connective tissue linkages between muscle-tendon units may act as an
additional mechanical constraint on the musculoskeletal system, thereby reducing
the spectrum of solutions for performing a motor task. We found that
intermuscular coordination changes following intermuscular connectivity
enhancement. Besides showing that the extent of such connectivity is taken into
account by the central nervous system, our results suggest that recruitment of
triceps surae muscles is governed by the moments produced at the ankle-knee
joints.
PMID- 28490644
TI - Background noise exerts diverse effects on the cortical encoding of foreground
sounds.
AB - In natural listening conditions, many sounds must be detected and identified in
the context of competing sound sources, which function as background noise.
Traditionally, noise is thought to degrade the cortical representation of sounds
by suppressing responses and increasing response variability. However, recent
studies of neural network models and brain slices have shown that background
synaptic noise can improve the detection of signals. Because acoustic noise
affects the synaptic background activity of cortical networks, it may improve the
cortical responses to signals. We used spike train decoding techniques to
determine the functional effects of a continuous white noise background on the
responses of clusters of neurons in auditory cortex to foreground signals,
specifically frequency-modulated sweeps (FMs) of different velocities,
directions, and amplitudes. Whereas the addition of noise progressively
suppressed the FM responses of some cortical sites in the core fields with
decreasing signal-to-noise ratios (SNRs), the stimulus representation remained
robust or was even significantly enhanced at specific SNRs in many others. Even
though the background noise level was typically not explicitly encoded in
cortical responses, significant information about noise context could be decoded
from cortical responses on the basis of how the neural representation of the
foreground sweeps was affected. These findings demonstrate significant diversity
in signal in noise processing even within the core auditory fields that could
support noise-robust hearing across a wide range of listening conditions.NEW &
NOTEWORTHY The ability to detect and discriminate sounds in background noise is
critical for our ability to communicate. The neural basis of robust perceptual
performance in noise is not well understood. We identified neuronal populations
in core auditory cortex of squirrel monkeys that differ in how they process
foreground signals in background noise and that may contribute to robust signal
representation and discrimination in acoustic environments with prominent
background noise.
PMID- 28490647
TI - Placebo and nocebo responses in restless legs syndrome: A systematic review and
meta-analysis.
AB - OBJECTIVE: To estimate the placebo and nocebo responses in restless legs syndrome
(RLS) and explore their determinants. METHODS: Databases were searched up to
October 2015. Randomized, double-blind, placebo-controlled trials of patients
with RLS were included if quantitative data were extractable in the placebo arm.
Placebo response was defined as the within-group change from baseline, using any
scale measuring RLS severity or disability. Nocebo response was defined as the
proportion of patients experiencing adverse events in the placebo arm. Random
effects meta-analysis was used to pool data. Statistical heterogeneity was
assessed with I2 statistic. Several predetermined subgroup and sensitivity
analysis were performed. PROSPERO registration number is CRD42015027992. RESULTS:
We included 85 randomized controlled trials (5,046 participants). Pooled placebo
response effect size was -1.41 (95% confidence interval [CI] -1.56 to -1.25, 64
trials, I2 = 88.1%), corresponding to -6.58 points in the International RLS Study
Group Scale (IRLS). Pooled nocebo response was 45.36% (95% CI 40.47%-50.29%, 72
trials; I2 = 89.8%). The placebo and nocebo responses were greater in trials with
longer duration, evaluating pharmacologic interventions and idiopathic RLS, and
in industry-funded and unpublished studies. The placebo response was considerably
smaller in objective as compared to subjective outcomes. In addition, the nocebo
response increases proportionally with the placebo response, and has the same
predictors. CONCLUSIONS: The magnitude of the placebo response in RLS is above
the threshold of minimal clinical important difference, and the frequency of
adverse events is also considerable. These results are relevant to inform the
design and interpretation of future clinical trials.
PMID- 28490646
TI - A missense mutation in Grm6 reduces but does not eliminate mGluR6 expression or
rod depolarizing bipolar cell function.
AB - GRM6 encodes the metabotropic glutamate receptor 6 (mGluR6) used by retinal
depolarizing bipolar cells (DBCs). Mutations in GRM6 lead to DBC dysfunction and
underlie the human condition autosomal recessive complete congenital stationary
night blindness. Mouse mutants for Grm6 are important models for this condition.
Here we report a new Grm6 mutant, identified in an electroretinogram (ERG) screen
of mice maintained at The Jackson Laboratory. The Grm6nob8 mouse has a reduced
amplitude b-wave component of the ERG, which reflects light-evoked DBC activity.
Sequencing identified a missense mutation that converts a highly conserved
methionine within the ligand binding domain to leucine (p.Met66Leu). Consistent
with prior studies of Grm6 mutant mice, the laminar size and structure in the
Grm6nob8 retina were comparable to control. The Grm6nob8 phenotype is
distinguished from other Grm6 mutants that carry a null allele by a reduced but
not absent ERG b-wave, decreased but present expression of mGluR6 at DBC
dendritic tips, and mislocalization of mGluR6 to DBC somas. Consistent with a
reduced but not absent b-wave, there were a subset of retinal ganglion cells
whose responses to light onset have times to peak within the range of those in
control retinas. These data indicate that the p.Met66Leu mutant mGluR6 is
trafficked less than control. However, the mGluR6 that is localized to the DBC
dendritic tips is able to initiate DBC signal transduction. The Grm6nob8 mouse
extends the Grm6 allelic series and will be useful for elucidating the role of
mGluR6 in DBC signal transduction and in human disease.NEW & NOTEWORTHY This
article describes a mouse model of the human disease complete congenital
stationary night blindness in which the mutation reduces but does not eliminate
GRM6 expression and bipolar cell function, a distinct phenotype from that seen in
other Grm6 mouse models.
PMID- 28490648
TI - Randomized trial of preladenant, given as monotherapy, in patients with early
Parkinson disease.
AB - OBJECTIVE: To evaluate the adenosine 2a receptor antagonist preladenant as a
nondopaminergic drug for the treatment of Parkinson disease (PD) when given as
monotherapy. METHODS: This was a randomized, 26-week, placebo- and active
controlled, parallel-group, multicenter, double-blind trial conducted in adults
diagnosed with PD for <5 years who were not yet receiving l-dopa or dopamine
agonists. Patients with a Unified Parkinson's Disease Rating Scale (UPDRS) part 3
(motor function) score >=10 and Hoehn & Yahr score <=3 were randomized 1:1:1:1:1
to preladenant 2, 5, or 10 mg twice daily, rasagiline 1 mg (active-control) once
daily, or placebo. The primary endpoint was the change from baseline at week 26
in the sum of UPDRS parts 2 (activities of daily living) and 3 scores (UPDRS2+3).
RESULTS: The number of patients treated was 1,007. Neither preladenant nor
rasagiline was superior to placebo after 26 weeks. The differences vs placebo
(95% confidence interval) in UPDRS2+3 scores (with a negative difference
indicating improvement vs placebo) were preladenant 2 mg = 2.60 (0.86, 4.30),
preladenant 5 mg = 1.30 (-0.41, 2.94), preladenant 10 mg = 0.40 (-1.29, 2.11),
and rasagiline 1 mg = 0.30 (-1.35, 2.03). Post hoc analyses did not identify a
single causal factor that could explain the finding of a failed trial.
Preladenant was generally well-tolerated with few patients discontinuing due to
adverse events (preladenant 7%, rasagiline 3%, placebo 4%). CONCLUSIONS: No
evidence supporting the efficacy of preladenant as monotherapy was observed in
this phase 3 trial. The lack of efficacy of the active control rasagiline makes
it difficult to interpret the results. CLINICAL TRIAL REGISTRATION:
Clinicaltrials.gov: NCT01155479. CLASSIFICATION OF EVIDENCE: This study provides
Class I evidence that for patients with early PD, preladenant is not effective as
monotherapy at the doses studied (2, 5, 10 mg).
PMID- 28490649
TI - Pathologic confirmation of retinal ganglion cell loss in multiple system atrophy.
PMID- 28490650
TI - The American Academy of Neurology affirms the revival of cooling for the revived.
PMID- 28490651
TI - Effects of MCI subtype and reversion on progression to dementia in a community
sample.
AB - OBJECTIVE: We sought to understand the trajectory of mild cognitive impairment
(MCI) better by examining longitudinally different MCI subtypes and progression
to dementia and reversion to normal cognition in a community sample. METHODS: We
evaluated the stability of MCI subtypes and risk of dementia over 4 biennial
assessments as part of an ongoing prospective cohort study, the Sydney Memory and
Ageing Study. RESULTS: While prevalence of MCI and different MCI subtypes remains
relatively stable across all assessments, reversion from MCI and transitions
between different MCI subtypes were common. Up to 46.5% of participants
classified with MCI at baseline reverted at some point during follow-up. The
majority (83.8%) of participants with incident dementia were diagnosed with MCI 2
years prior to their dementia diagnosis. Both reverters and participants with
stable MCI were at an increased risk of progression to dementia compared to those
without MCI at baseline (HR 6.4, p = 0.02, and HR 24.7, p < 0.001, respectively);
however, the risk of dementia in participants with MCI who did not revert was
higher than in reverters (HR 2.5, p = 0.01). This effect was specific to amnestic
subtypes (MCI reverters vs nonreverters: amnestic MCI HR 3.3, p = 0.006;
nonamnestic MCI: HR 1.3, p = 0.67). CONCLUSION: Our findings indicate that the
relevance of reversion for progression risk depends on the MCI subtype. Subtype
specificity and longitudinal characterization are required for the reliable
identification of individuals at high risk of developing dementia.
PMID- 28490652
TI - Restless legs syndrome: Losing sleep over the placebo response.
PMID- 28490653
TI - Prospective association between beta2-microglobulin levels and ischemic stroke
risk among women.
AB - OBJECTIVE: To determine whether elevated beta2-microglobulin (B2M) levels were
associated with an increased risk of incident ischemic stroke events among women.
METHODS: We performed a nested case-control study among women enrolled in the
Nurses' Health Study who provided blood samples between 1989 and 1990 and were
free of prior stroke and cancer. We measured B2M levels in 473 ischemic strokes
cases confirmed by medical record review and in 473 controls matched 1:1 to the
cases on age, race, date of blood collection, menopausal status, postmenopausal
hormone use, and smoking status. We analyzed the association between B2M and
ischemic stroke using multivariable conditional logistic regression to adjust for
traditional stroke risk factors. RESULTS: Median levels of B2M were higher among
cases (1.86 mg/L) than controls (1.80 mg/L, p = 0.009, Wilcoxon rank-sum test).
Women in the highest B2M quartile had a multivariable-adjusted increased risk of
ischemic stroke compared to those in the lowest quartile (odds ratio [OR] 1.56,
95% confidence interval [CI] 1.02-2.39). Results were similar when restricted to
those without evidence of chronic kidney disease (estimated glomerular filtration
rate >=60 mL.min-1.1.73 m-2) (OR 1.49, 95% CI 1.08-2.06). In an exploratory
analysis, the association between B2M and thrombotic stroke was similar to the
overall ischemic stroke results, but no association was observed for embolic
stroke risk. CONCLUSION: High levels of B2M were associated with an increased
risk of ischemic stroke among women.
PMID- 28490654
TI - Early skin denervation in hereditary and iatrogenic transthyretin amyloid
neuropathy.
AB - OBJECTIVE: To elucidate early skin denervation in hereditary transthyretin (TTR)
amyloidosis and iatrogenic TTR amyloidosis. METHODS: We investigated
intraepidermal nerve fiber density (IENFD) and clinical findings in 32 patients
with hereditary TTR amyloidosis, 11 asymptomatic mutation carriers, 6 patients
with iatrogenic TTR amyloidosis, and 23 healthy volunteers. RESULTS: IENFD values
were reduced in patients with the V30M mutation (1.9 +/- 2.1 per 1 mm), patients
with non-V30M mutations (5.8 +/- 3.2 per 1 mm), and patients with iatrogenic TTR
amyloidosis (3.5 +/- 1.8 per 1 mm) compared with healthy volunteers (11.8 +/- 3.2
per 1 mm) (p < 0.01). Skin denervation also occurred, even in presymptomatic V30M
mutation carriers (5.0 +/- 2.2 per 1 mm). The IENFD was correlated with disease
duration (rho = -0.533, p = 0.002) and various peripheral neuropathy parameters
such as sensory impairment in the Kumamoto clinical score (rho = -0.575, p =
0.001), heat-pain detection threshold (rho = -0.704, p < 0.001), and sural
sensory nerve action potential (rho = 0.481, p = 0.005). TTR amyloid deposits
frequently occurred in connective tissues and vessels of the dermal reticular
layer in patients with hereditary TTR amyloidosis and those with iatrogenic TTR
amyloidosis. CONCLUSIONS: Patients with hereditary TTR amyloidosis and those with
iatrogenic TTR amyloidosis may show early skin denervation even in the
presymptomatic stage. IENFD may thus be useful for early diagnosis and may serve
as a biomarker in clinical trials for hereditary and iatrogenic TTR amyloidosis.
PMID- 28490655
TI - Practice guideline summary: Reducing brain injury following cardiopulmonary
resuscitation: Report of the Guideline Development, Dissemination, and
Implementation Subcommittee of the American Academy of Neurology.
AB - OBJECTIVE: To assess the evidence and make evidence-based recommendations for
acute interventions to reduce brain injury in adult patients who are comatose
after successful cardiopulmonary resuscitation. METHODS: Published literature
from 1966 to August 29, 2016, was reviewed with evidence-based classification of
relevant articles. RESULTS AND RECOMMENDATIONS: For patients who are comatose in
whom the initial cardiac rhythm is either pulseless ventricular tachycardia (VT)
or ventricular fibrillation (VF) after out-of-hospital cardiac arrest (OHCA),
therapeutic hypothermia (TH; 32-34 degrees C for 24 hours) is highly likely to be
effective in improving functional neurologic outcome and survival compared with
non-TH and should be offered (Level A). For patients who are comatose in whom the
initial cardiac rhythm is either VT/VF or asystole/pulseless electrical activity
(PEA) after OHCA, targeted temperature management (36 degrees C for 24 hours,
followed by 8 hours of rewarming to 37 degrees C, and temperature maintenance
below 37.5 degrees C until 72 hours) is likely as effective as TH and is an
acceptable alternative (Level B). For patients who are comatose with an initial
rhythm of PEA/asystole, TH possibly improves survival and functional neurologic
outcome at discharge vs standard care and may be offered (Level C). Prehospital
cooling as an adjunct to TH is highly likely to be ineffective in further
improving neurologic outcome and survival and should not be offered (Level A).
Other pharmacologic and nonpharmacologic strategies (applied with or without
concomitant TH) are also reviewed.
PMID- 28490656
TI - Role of habenula and amygdala dysfunction in Parkinson disease patients with
punding.
AB - OBJECTIVE: To assess whether a functional dysregulation of the habenula and
amygdala, as modulators of the reward brain circuit, contributes to Parkinson
disease (PD) punding. METHODS: Structural and resting-state functional MRI were
obtained from 22 patients with PD punding, 30 patients with PD without any
impulsive-compulsive behavior (ICB) matched for disease stage and duration, motor
impairment, and cognitive status, and 30 healthy controls. Resting-state
functional connectivity of the habenula and amygdala bilaterally was assessed
using a seed-based approach. Habenula and amygdala volumes and cortical thickness
measures were obtained. RESULTS: Compared to both healthy controls and PD cases
without any ICB (PD-no ICB), PD-punding patients showed higher functional
connectivity of habenula and amygdala with thalamus and striatum bilaterally, and
lower connectivity between bilateral habenula and left frontal and precentral
cortices. In PD-punding relative to PD-no ICB patients, a lower functional
connectivity between right amygdala and hippocampus was also observed. Habenula
and amygdala volumes were not different among groups. PD-punding patients showed
a cortical thinning of the left superior frontal and precentral gyri and right
middle temporal gyrus and isthmus cingulate compared to healthy controls, and of
the right inferior frontal gyrus compared to both controls and PD-no ICB
patients. CONCLUSIONS: A breakdown of the connectivity among the crucial nodes of
the reward circuit (i.e., habenula, amygdala, basal ganglia, frontal cortex)
might be a contributory factor to punding in PD. This study provides potential
instruments to detect and monitor punding in patients with PD.
PMID- 28490657
TI - Targeting endogenous proteins for degradation through the affinity-directed
protein missile system.
AB - Targeted proteolysis of endogenous proteins is desirable as a research toolkit
and in therapeutics. CRISPR/Cas9-mediated gene knockouts are irreversible and
often not feasible for many genes. Similarly, RNA interference approaches
necessitate prolonged treatments, can lead to incomplete knockdowns and are often
associated with off-target effects. Targeted proteolysis can overcome these
limitations. In this report, we describe an affinity-directed protein missile
(AdPROM) system that harbours the von Hippel-Lindau (VHL) protein, the substrate
receptor of the Cullin2 (CUL2) E3 ligase complex, tethered to polypeptide binders
that selectively bind and recruit endogenous target proteins to the CUL2-E3
ligase complex for ubiquitination and proteasomal degradation. By using synthetic
monobodies that selectively bind the protein tyrosine phosphatase SHP2 and a
camelid-derived VHH nanobody that selectively binds the human ASC protein, we
demonstrate highly efficient AdPROM-mediated degradation of endogenous SHP2 and
ASC in human cell lines. We show that AdPROM-mediated loss of SHP2 in cells
impacts SHP2 biology. This study demonstrates for the first time that small
polypeptide binders that selectively recognize endogenous target proteins can be
exploited for AdPROM-mediated destruction of the target proteins.
PMID- 28490659
TI - RUNX transcription factors at the interface of stem cells and cancer.
AB - The RUNX1 transcription factor is a critical regulator of normal haematopoiesis
and its functional disruption by point mutations, deletions or translocations is
a major causative factor leading to leukaemia. In the majority of cases, genetic
changes in RUNX1 are linked to loss of function classifying it broadly as a
tumour suppressor. Despite this, several recent studies have reported the need
for a certain level of active RUNX1 for the maintenance and propagation of acute
myeloid leukaemia and acute lymphoblastic leukaemia cells, suggesting an
oncosupportive role of RUNX1. Furthermore, in solid cancers, RUNX1 is
overexpressed compared with normal tissue, and RUNX factors have recently been
discovered to promote growth of skin, oral, breast and ovarian tumour cells,
amongst others. RUNX factors have key roles in stem cell fate regulation during
homeostasis and regeneration of many tissues. Cancer cells appear to have
corrupted these stem cell-associated functions of RUNX factors to promote
oncogenesis. Here, we discuss current knowledge on the role of RUNX genes in stem
cells and as oncosupportive factors in haematological malignancies and epithelial
cancers.
PMID- 28490660
TI - Hiding in plain sight: immune evasion by the staphylococcal protein SdrE.
AB - The human immune system is responsible for identification and destruction of
invader cells, such as the bacterial pathogen Staphylococcus aureus In response,
S. aureus brings to the fight a large number of virulence factors, including
several that allow it to evade the host immune response. The staphylococcal
surface protein SdrE was recently reported to bind to complement Factor H, an
important regulator of complement activation. Factor H attaches to the surface of
host cells to inhibit complement activation and amplification, preventing the
destruction of the host cell. SdrE binding to Factor H allows S. aureus to mimic
a host cell and reduces bacterial killing by granulocytes. In a new study
published in Biochemical Journal, Zhang et al. describe crystal structures of
SdrE and its complex with the C-terminal portion of Factor H. The structure of
SdrE and its interaction with the Factor H peptide closely resemble a family of
surface proteins that recognize extracellular matrix components such as
fibrinogen. However, unbound SdrE forms a novel 'Closed' conformation with an
occluded peptide-binding groove. These structures reveal a fascinating mechanism
for immune evasion and provide a potential avenue for the development of novel
antimicrobial agents to target SdrE.
PMID- 28490661
TI - Surgery for subacromial impingement syndrome in relation to occupational
exposures, lifestyle factors and diabetes mellitus: a nationwide nested case
control study.
AB - OBJECTIVES: To estimate the risk of surgery for subacromial impingement syndrome
(SIS) in relation to occupational exposures, lifestyle factors and diabetes
mellitus. METHODS: We conducted a case-control study nested in a register-based
cohort study of the Danish working population. For each of 3000 first-time cases
of surgery for SIS, two age-matched and sex-matched controls were drawn. Cases
and controls received a questionnaire on job history and other factors. Job
histories were combined with a psychosocial job exposure matrix (JEM) and the
updated Shoulder JEM, which provided exposure intensities on measurement scales.
Ten-year cumulative exposures to upper arm elevation >90 degrees , repetitive
shoulder movements, forceful shoulder exertions and hand-arm vibrations (HAVs)
were estimated. We used conditional logistic regression. RESULTS: There were 5396
persons (60%) who answered the questionnaire. For occupational mechanical
exposures, the adjusted OR (ORadj) ranged from 1.9 (95% CI 1.5 to 2.5 for HAVs)
to 2.5 (95% CI 1.9 to 3.5 for force) among men and 1.7 (95% CI 1.2 to 2.5 for
HAVs) to 2.0 (95% CI 1.3 to 2.9 for force) among women. No statistically
significant associations were found for occupational psychosocial factors. Body
mass index (BMI) and pack-years of smoking showed ORadj up to 2.0. Diabetes
mellitus showed ORadj of 1.5 (95% CI 1.1 to 2.2) for men and 2.2 (95% CI 1.4 to
3.4) for women. CONCLUSIONS: Our findings add to the evidence of an increased
risk of surgery for SIS in relation to occupational cumulative mechanical
exposures, even when an increased risk in relation to BMI, smoking and diabetes
mellitus is taken into account.
PMID- 28490662
TI - Occupational exposure to endotoxins and lung cancer risk: results of the ICARE
Study.
AB - OBJECTIVES: To investigate the role of occupational exposure to endotoxins in
lung cancer in a French population-based case-control study (ICARE (Investigation
of occupational and environmental causes of respiratory cancers)). METHODS:
Detailed information was collected on the occupational history and smoking habits
from 2926 patients with histologically confirmed lung cancer and 3555 matched
controls. We evaluated each subject's endotoxin exposure after cross referencing
International Standard Classification of Occupations (ISCO) codes (for job tasks)
and Nomenclature d'Activites Francaises (NAF) codes (for activity sectors).
Endotoxin exposure levels were attributed to each work environment based on
literature reports. ORs and 95% CIs were estimated using unconditional logistic
regression models and controlled for main confounding factors. RESULTS: An
inverse association between exposure to endotoxins and lung cancer was found
(OR=0.80, 95% CI 0.66 to 0.95). Negative trends were shown with duration and
cumulative exposure, and the risk was decreased decades after exposure cessation
(all statistically significant). Lung cancer risk was particularly reduced among
workers highly exposed (eg, in dairy, cattle, poultry, pig farms), but also in
those weakly exposed (eg, in waste treatment). Statistically significant
interactions were shown with smoking, and never/light smokers were more sensitive
to an endotoxin effect than heavy smokers (eg, OR=0.14, 95% CI 0.06 to 0.32 and
OR=0.80, 95% CI 0.45 to 1.40, respectively, for the quartiles with the highest
cumulative exposure, compared with those never exposed). Pronounced inverse
associations were shown with adenocarcinoma histological subtype (OR=0.37, 95% CI
0.25 to 0.55 in the highly exposed). CONCLUSIONS: Our findings suggest that
exposure to endotoxins, even at a low level, reduces the risk of lung cancer.
PMID- 28490663
TI - Quantitative estimated exposure to vinyl chloride and risk of angiosarcoma of the
liver and hepatocellular cancer in the US industry-wide vinyl chloride cohort:
mortality update through 2013.
AB - OBJECTIVE: To evaluate mortality risks of angiosarcoma of the liver (ASL),
primary hepatocellular carcinoma (HCC) and other cancers among 9951 men employed
between 1942 and 1972 at 35 US vinyl chloride (VC) or polyvinyl chloride plants
followed for mortality through 31 December 2013. METHODS: SMR and time-dependent
Cox proportional hazards analyses were used to evaluate mortality risks by
cumulative VC exposure. RESULTS: Liver cancer mortality was elevated (SMR=2.87,
95% CI 2.40 to 3.40), and ASL and HCC were strongly associated with cumulative VC
exposure >=865 parts per million-years (ppm-years) (ASL: HR=36.3, 95% CI 13.1 to
100.5; and HCC: HR=5.3, 95% CI 1.6 to 17.7 for >=2271 ppm-years). Excess deaths
due to connective and soft tissue cancers (SMR=2.43, 95% CI 1.48 to 3.75),
mesothelioma (SMR=2.29, 95% CI 1.18 to 4.00) and explosions (SMR=3.43, 95% CI
1.25 to 7.47) were seen. Mortalities due to melanoma, brain cancer, lung cancer
and non-Hodgkin's lymphoma were not increased or associated with VC exposure.
CONCLUSION: The association between VC and ASL first reported in this cohort 44
years ago persisted and was strongest among workers most highly exposed. VC
exposure also was associated with HCC mortality, although it remains possible
that misdiagnosis of early ASLs influenced findings.
PMID- 28490664
TI - Inhibiting the oncogenic translation program is an effective therapeutic strategy
in multiple myeloma.
AB - Multiple myeloma (MM) is a frequently incurable hematological cancer in which
overactivity of MYC plays a central role, notably through up-regulation of
ribosome biogenesis and translation. To better understand the oncogenic program
driven by MYC and investigate its potential as a therapeutic target, we screened
a chemically diverse small-molecule library for anti-MM activity. The most potent
hits identified were rocaglate scaffold inhibitors of translation initiation.
Expression profiling of MM cells revealed reversion of the oncogenic MYC-driven
transcriptional program by CMLD010509, the most promising rocaglate. Proteome
wide reversion correlated with selective depletion of short-lived proteins that
are key to MM growth and survival, most notably MYC, MDM2, CCND1, MAF, and MCL-1.
The efficacy of CMLD010509 in mouse models of MM confirmed the therapeutic
relevance of these findings in vivo and supports the feasibility of targeting the
oncogenic MYC-driven translation program in MM with rocaglates.
PMID- 28490666
TI - The path of least antibiotic resistance.
AB - Antibiotic combination therapy alters Mycobacterium tuberculosis population
dynamics in the human host.
PMID- 28490665
TI - In vivo imaging reveals a tumor-associated macrophage-mediated resistance pathway
in anti-PD-1 therapy.
AB - Monoclonal antibodies (mAbs) targeting the immune checkpoint anti-programmed cell
death protein 1 (aPD-1) have demonstrated impressive benefits for the treatment
of some cancers; however, these drugs are not always effective, and we still have
a limited understanding of the mechanisms that contribute to their efficacy or
lack thereof. We used in vivo imaging to uncover the fate and activity of aPD-1
mAbs in real time and at subcellular resolution in mice. We show that aPD-1 mAbs
effectively bind PD-1+ tumor-infiltrating CD8+ T cells at early time points after
administration. However, this engagement is transient, and aPD-1 mAbs are
captured within minutes from the T cell surface by PD-1- tumor-associated
macrophages. We further show that macrophage accrual of aPD-1 mAbs depends both
on the drug's Fc domain glycan and on Fcgamma receptors (FcgammaRs) expressed by
host myeloid cells and extend these findings to the human setting. Finally, we
demonstrate that in vivo blockade of FcgammaRs before aPD-1 mAb administration
substantially prolongs aPD-1 mAb binding to tumor-infiltrating CD8+ T cells and
enhances immunotherapy-induced tumor regression in mice. These investigations
yield insight into aPD-1 target engagement in vivo and identify specific
Fc/FcgammaR interactions that can be modulated to improve checkpoint blockade
therapy.
PMID- 28490667
TI - Working memory: The real VIP.
AB - Interneurons expressing VIP may play a causal role in working memory.
PMID- 28490668
TI - "TrkA"cking why "no pain, no gain" is the rule for bone formation.
AB - Peripheral sensory nerves expressing TrkA innervate long bones and stimulate bone
formation through the Wnt/beta-catenin pathway when placed under stress.
PMID- 28490669
TI - HIV-associated anaerobes ferment TB risk.
AB - Short-chain fatty acids produced by anaerobic bacteria increase the risk of TB in
HIV-infected, antiretroviral drug-treated people.
PMID- 28490670
TI - Leukotriene B4 antagonism ameliorates experimental lymphedema.
AB - Acquired lymphedema is a cancer sequela and a global health problem currently
lacking pharmacologic therapy. We have previously demonstrated that ketoprofen,
an anti-inflammatory agent with dual 5-lipoxygenase and cyclooxygenase inhibitory
properties, effectively reverses histopathology in experimental lymphedema. We
show that the therapeutic benefit of ketoprofen is specifically attributable to
its inhibition of the 5-lipoxygenase metabolite leukotriene B4 (LTB4). LTB4
antagonism reversed edema, improved lymphatic function, and restored lymphatic
architecture in the murine tail model of lymphedema. In vitro, LTB4 was
functionally bimodal: Lower LTB4 concentrations promoted human lymphatic
endothelial cell sprouting and growth, but higher concentrations inhibited
lymphangiogenesis and induced apoptosis. During lymphedema progression, lymphatic
fluid LTB4 concentrations rose from initial prolymphangiogenic concentrations
into an antilymphangiogenic range. LTB4 biosynthesis was similarly elevated in
lymphedema patients. Low concentrations of LTB4 stimulated, whereas high
concentrations of LTB4 inhibited, vascular endothelial growth factor receptor 3
and Notch pathways in cultured human lymphatic endothelial cells. Lymphatic
specific Notch1-/- mice were refractory to the beneficial effects of LTB4
antagonism, suggesting that LTB4 suppression of Notch signaling is an important
mechanism in disease maintenance. In summary, we found that LTB4 was harmful to
lymphatic repair at the concentrations observed in established disease. Our
findings suggest that LTB4 is a promising drug target for the treatment of
acquired lymphedema.
PMID- 28490671
TI - Matched preclinical designs for improved translatability.
AB - A more stratified preclinical design strategy will increase the statistical power
and reproducibility of animal studies and their translatability.
PMID- 28490673
TI - Development and Evaluation of the National Cancer Institute's Dietary Screener
Questionnaire Scoring Algorithms.
AB - Background: Methods for improving the utility of short dietary assessment
instruments are needed.Objective: We sought to describe the development of the
NHANES Dietary Screener Questionnaire (DSQ) and its scoring algorithms and
performance.Methods: The 19-item DSQ assesses intakes of fruits and vegetables,
whole grains, added sugars, dairy, fiber, and calcium. Two nonconsecutive 24-h
dietary recalls and the DSQ were administered in NHANES 2009-2010 to respondents
aged 2-69 y (n = 7588). The DSQ frequency responses, coupled with sex- and age
specific portion size information, were regressed on intake from 24-h recalls by
using the National Cancer Institute usual intake method to obtain scoring
algorithms to estimate mean and prevalences of reaching 2 a priori threshold
levels. The resulting scoring algorithms were applied to the DSQ and compared
with intakes estimated with the 24-h recall data only. The stability of the
derived scoring algorithms was evaluated in repeated sampling. Finally, scoring
algorithms were applied to screener data, and these estimates were compared with
those from multiple 24-h recalls in 3 external studies.Results: The DSQ and its
scoring algorithms produced estimates of mean intake and prevalence that agreed
closely with those from multiple 24-h recalls. The scoring algorithms were stable
in repeated sampling. Differences in the means were <2%; differences in
prevalence were <16%. In other studies, agreement between screener and 24-h
recall estimates in fruit and vegetable intake varied. For example, among men in
2 studies, estimates from the screener were significantly lower than the 24-h
recall estimates (3.2 compared with 3.8 and 3.2 compared with 4.1). In the third
study, agreement between the screener and 24-h recall estimates were close among
both men (3.2 compared with 3.1) and women (2.6 compared with 2.5).Conclusions:
This approach to developing scoring algorithms is an advance in the use of
screeners. However, because these algorithms may not be generalizable to all
studies, a pilot study in the proposed study population is advisable. Although
more precise instruments such as 24-h dietary recalls are recommended in most
research, the NHANES DSQ provides a less burdensome alternative when time and
resources are constrained and interest is in a limited set of dietary factors.
PMID- 28490674
TI - Physical Form of Dietary Fat Alters Postprandial Substrate Utilization and
Glycemic Response in Healthy Chinese Men.
AB - Background: Dietary fats elicit various physiological responses, with the
physical form of fat reported to alter fat digestion and absorption.Objectives:
The primary aims were to compare the effects of dietary fat in 2 physical forms
(liquid and oleogel) and 2 degrees of saturation (saturated and polyunsaturated)
on postprandial energy expenditure (EE) and substrate oxidation, glycemia, and
appetite.Methods: The study was a randomized, controlled crossover trial. Sixteen
normal-weight, healthy Chinese men completed the study [mean +/- SD age: 28 +/- 6
y; body mass index (in kg/m2): 22.9 +/- 3.1]. After an overnight fast,
participants had their body weight measured and entered an indirect whole-room
calorimeter (WRC). After baseline measurements, participants consumed orange
juice and rice porridge alone (control), with 22.25 g coconut oil or sunflower
oil or with 25 g coconut oleogel or sunflower oleogel in random order with a 5-d
washout period between treatments. EE, substrate oxidation, capillary blood
glucose, and appetite were measured over 195 min in a WRC. Participants completed
a meal challenge to assess appetite. Test meals effects were compared by using
repeated-measures ANOVA.Results: Fat saturation did not affect all study outcomes
significantly. When data were pooled based on the physical form of dietary fat,
EE did not differ. However, significantly higher carbohydrate oxidation (P =
0.03) and a trend of lower fat oxidation (P = 0.07) were found after the liquid
oil than after the oleogel or control treatments. Postprandial capillary glucose
was also significantly lower after the liquid oil than after the oleogel or
control treatments (P < 0.001). Appetite was not affected by the physical form
and the saturation of dietary fats.Conclusions: The saturation of dietary fat did
not affect postprandial glucose, EE, substrate oxidation, or appetite. However,
oleogel prevented the glycemic-lowering and fat-oxidation effects induced by
liquid oil in Chinese men. Future work on oleogel should focus on cardiometabolic
risk factors. This study was registered at clinicaltrials.gov as NCT02702726.
PMID- 28490672
TI - Phenome-wide scanning identifies multiple diseases and disease severity
phenotypes associated with HLA variants.
AB - Although many phenotypes have been associated with variants in human leukocyte
antigen (HLA) genes, the full phenotypic impact of HLA variants across all
diseases is unknown. We imputed HLA genomic variation from two populations of
28,839 and 8431 European ancestry individuals and tested association of HLA
variation with 1368 phenotypes. A total of 104 four-digit and 92 two-digit HLA
allele phenotype associations were significant in both discovery and replication
cohorts, the strongest being HLA-DQB1*03:02 and type 1 diabetes. Four previously
unidentified associations were identified across the spectrum of disease with two
and four-digit HLA alleles and 10 with nonsynonymous variants. Some conditions
associated with multiple HLA variants and stronger associations with more severe
disease manifestations were identified. A comprehensive, publicly available
catalog of clinical phenotypes associated with HLA variation is provided.
Examining HLA variant disease associations in this large data set allows
comprehensive definition of disease associations to drive further mechanistic
insights.
PMID- 28490675
TI - Identification of a Hemolysis Threshold That Increases Plasma and Serum Zinc
Concentration.
AB - Background: Plasma or serum zinc concentration (PZC or SZC) is the primary
measure of zinc status, but accurate sampling requires controlling for hemolysis
to prevent leakage of zinc from erythrocytes. It is not established how much
hemolysis can occur without changing PZC/SZC concentrations.Objective: This study
determines a guideline for the level of hemolysis that can significantly elevate
PZC/SZC.Methods: The effect of hemolysis on PZC/SZC was estimated by using
standard hematologic variables and mineral content. The calculated hemolysis
threshold was then compared with results from an in vitro study and a population
survey. Hemolysis was assessed by hemoglobin and iron concentrations, direct
spectrophotometry, and visual assessment of the plasma or serum. Zinc and iron
concentrations were determined by inductively coupled plasma
spectrometry.Results: A 5% increase in PZC/SZC was calculated to result from the
lysis of 1.15% of the erythrocytes in whole blood, corresponding to ~1 g
hemoglobin/L added into the plasma or serum. Similarly, the addition of simulated
hemolysate to control plasma in vitro caused a 5% increase in PZC when hemoglobin
concentrations reached 1.18 +/- 0.10 g/L. In addition, serum samples from a
population nutritional survey were scored for hemolysis and analyzed for changes
in SZC; samples with hemolysis in the range of 1-2.5 g hemoglobin/L showed an
estimated increase in SZC of 6% compared with nonhemolyzed samples. Each approach
indicated that a 5% increase in PZC/SZC occurs at ~1 g hemoglobin/L in plasma or
serum. This concentration of hemoglobin can be readily identified directly by
chemical hemoglobin assays or indirectly by direct spectrophotometry or matching
to a color scale.Conclusions: A threshold of 1 g hemoglobin/L is recommended for
PZC/SZC measurements to avoid increases in zinc caused by hemolysis. The use of
this threshold may improve zinc assessment for monitoring zinc status and
nutritional interventions.
PMID- 28490676
TI - Excretion of Zinc and Copper Increases in Men during 3 Weeks of Bed Rest, with or
without Artificial Gravity.
AB - Background: Zinc and copper have many physiologic functions and little or no
functional storage capability, so persistent losses of either element present
health concerns, especially during extended-duration space missions.Objectives:
We evaluated the effects of short-term bed rest (BR), a spaceflight analog, on
copper and zinc metabolism to better understand the role of these nutrients in
human adaptation to (simulated) spaceflight. We also investigated the effect of
artificial gravity on copper and zinc homeostasis.Methods: Zinc and copper
balances were studied in 15 men [mean +/- SD age: 29 +/- 3 y; body mass index (in
kg/m2): 26.4 +/- 2.2] before, during, and after 21 d of head-down tilt BR, during
which 8 of the participants were subjected to artificial gravity (AG) by
centrifugation for 1 h/d. Control subjects were transferred onto the centrifuge
but were not exposed to centrifugation. The study was conducted in a metabolic
ward; all urine and feces were collected. Data were analyzed by 2-factor repeated
measures ANOVA.Results: Urinary zinc excretion values for control and AG groups
were 33% and 14%, respectively, higher during BR than before BR, and fecal zinc
excretion values for control and AG groups were 36% and 19%, respectively, higher
during BR, resulting in 67% and 82% lower net zinc balances for controls and AG,
respectively (both P < 0.01), despite lower nutrient intake during BR. Fecal
copper values for control and AG groups were 40% and 33%, respectively, higher
during BR than before BR (P < 0.01 for both). Urinary copper did not change
during BR, but a 19% increase was observed after BR compared with before BR in
the AG group (P < 0.05).Conclusions: The increased fecal excretion of copper and
zinc by men during BR suggests that their absorption of these minerals from the
diet was reduced, secondary to the release of minerals from bone and muscle.
These findings highlight the importance of determining dietary requirements for
astronauts on space missions and ensuring provision and intake of all nutrients.
PMID- 28490678
TI - Implications of US Nutrition Facts Label Changes on Micronutrient Density of
Fortified Foods and Supplements.
AB - The US FDA published new nutrition-labeling regulations in May 2016. For the
first time since the implementation of the Nutrition Labeling and Education Act
of 1990, the Daily Value (DV) for most vitamins will change, as will the units of
measurement used in nutrition labeling for some vitamins. For some food
categories, the Reference Amounts Customarily Consumed (RACCs) will increase to
reflect portions commonly consumed on a single occasion. These regulatory changes
are now effective, and product label changes will be mandatory beginning 26 July
2018. This commentary considers the potential impact of these regulatory changes
on the vitamin and mineral contents of foods and dietary supplements. Case
studies examined potential effects on food fortification and nutrient density.
The updated DVs may lead to a reduction in the nutrient density of foods and
dietary supplements with respect to 8 vitamins (vitamin A, thiamin, riboflavin,
niacin, vitamin B-6, vitamin B-12, biotin, and pantothenic acid) and 6 minerals
(zinc, selenium, copper, chromium, molybdenum, and chloride), and have mixed
effects on 2 vitamins where the amount required per serving is affected by
chemical structure (i.e., form) (natural vitamin E compared with synthetic
vitamin E and folic acid compared with folate). Despite an increased DV for
vitamin D, regulations limit food fortification. The adoption of Dietary Folate
Equivalents for folate labeling may lead to reductions in the quantity of folic
acid voluntarily added per RACC. Finally, because of increased RACCs in some food
categories to reflect portions that people typically eat at one time, the vitamin
and mineral density of these foods may be affected adversely. In totality, the
United States is entering an era in which the need to monitor dietary intake
patterns and nutritional status is unprecedented.
PMID- 28490677
TI - Dietary Human Milk Oligosaccharides but Not Prebiotic Oligosaccharides Increase
Circulating Natural Killer Cell and Mesenteric Lymph Node Memory T Cell
Populations in Noninfected and Rotavirus-Infected Neonatal Piglets.
AB - Background: Human milk oligosaccharides (HMOs) have antimicrobial and
immunomodulatory actions. It has previously been reported that these
oligosaccharides contribute to the reduced duration of rotavirus-induced diarrhea
in pigs.Objective: We measured the effects of HMOs and prebiotic oligosaccharides
on immune cell populations from noninfected and rotavirus-infected pigs. We
hypothesized that dietary HMOs would modulate systemic and gastrointestinal
immunity.Methods: Colostrum-deprived newborn pigs were fed formula, formula with
4 g HMOs/L (2'-fucosyllactose, lacto-N-neotetraose, 6'-sialyllactose, 3'
sialyllactose, and free sialic acid), or formula with 3.6 g short-chain
galactooligosaccharides/L and 0.4 g long-chain fructooligosaccharides/L. On day
10, half of the pigs were infected with the porcine rotavirus strain OSU.
Peripheral blood mononuclear cell (PBMC), mesenteric lymph node (MLN), and ileal
Peyer's patch immune cell populations were assessed with the use of flow
cytometry 5 d postinfection. Interferon-gamma (IFN-gamma)-producing cells were
assessed with the use of Enzyme-Linked ImmunoSpot assay.Results: Infection
changed immune cell populations with more systemic natural killer (NK) cells,
memory effector T cells, and major histocompatibility complex II+ cells in
infected than noninfected pigs (P < 0.06). Regardless of infection status, HMO
fed pigs had nearly twice as many PBMC NK cells, 36% more MLN effector memory T
cells, and 5 times more PBMC basophils than formula-fed pigs (P < 0.04). These
populations were intermediate in pigs fed prebiotics. PBMCs from HMO-fed
noninfected pigs had twice as many IFN-gamma-producing cells as did those from
formula-fed noninfected pigs (P = 0.017). The PBMCs and MLNs of formula-fed
noninfected pigs had 3 times more plasmacytoid dendritic cells (pDCs) than those
of HMO-fed noninfected and formula-fed infected pigs (P < 0.04). In the MLNs, the
formula-fed noninfected pigs had more macrophages, pDCs, and mature DCs (P <
0.04) but fewer immature DCs than HMO-fed noninfected pigs (P =
0.022).Conclusions: Dietary HMOs were more effective than prebiotics in altering
systemic and gastrointestinal immune cells in pigs. These altered immune cell
populations may mediate the effects of dietary HMOs on rotavirus infection
susceptibility.
PMID- 28490679
TI - [Issues on the Intraoperative Motor Evoked Potential Monitoring in Neurosurgery].
PMID- 28490680
TI - [A Ruptured Aneurysm at the Origin of a Duplicated Middle Cerebral Artery,
Treated by Coil Embolization:A Case Report].
AB - Duplication of the middle cerebral artery(MCA)is an anatomical variant of the
MCA, originating from the distal portion of the internal carotid artery(ICA)and
supplying blood flow to the tip of the temporal lobe. Cerebral aneurysms rarely
develop at the bifurcation of the ICA and the duplicated MCA, but when they do
develop, they may result in subarachnoid hemorrhage. We treated a 41-year-old
man, who was urgently brought to our hospital because of severe headache. A
computed tomography(CT)scan showed subarachnoid hemorrhage due to the rupture of
an aneurysm at the origin of the duplicated MCA. The aneurysm was small and
projected laterally, and coil embolization was performed employing a balloon
catheter. The neck of the aneurysm was not embolized to preserve the origin of
the duplicated MCA. The patient had an uneventful postoperative course, and he
returned to his usual daily activities. Coil embolization is rapidly developing
for treatment of cerebral aneurysms and may be the first-line treatment for
duplicated MCA aneurysms. Owing to the relatively small size of such aneurysms,
the risk of intraprocedural rupture should be considered, and a carefully
performed balloon-assisted procedure is recommended.
PMID- 28490681
TI - [Hemorrhagic Onset of Subependymal Giant Cell Astrocytoma Associated with
Tuberous Sclerosis:A Case Report and Review of Literature].
AB - We report on a case of subependymal giant cell astrocytoma(SEGA)in a patient with
tuberous sclerosis(TSC)that presented with intratumoral hemorrhage and acute
hydrocephalus. Initial treatment was external ventricular drainage to control the
intracranial pressure;however, the tumor increased in size due to recurrent
hemorrhage. Subsequently, the tumor was successfully removed via the
transcortical-transventricular approach without neurological deterioration.
Although intratumoral hemorrhage is extremely rare in patients with SEGA,
subsequent acute hydrocephalus resulting from obstruction of the foramen of Monro
will be fatal if prompt surgical treatment is not available. Careful and
periodical radiographic examination of the central nervous system will be
mandatory in patients with TSC, especially in those who have subependymal
nodules(SEN)or SEGA around the foramen of Monro. Radical surgical removal should
be considered before they become symptomatic.
PMID- 28490682
TI - [Association of Lower limb Neuropathy with Lumboperitoneal Shunt Transection:A
Case Report].
AB - A 49-year-old woman suffered hydrocephalus after subarachnoid hemorrhage, and
underwent a lumboperitoneal(LP)shunt operation. X-ray imaging revealed that a
spinal catheter inserted into the cranial side from L2/3 turned caudally at the
Th12 level. Postoperative numbness and pain of the left buttocks and posterior
femoral region persisted. The spinal catheter was pulled about 5 cm to improve
flexure, and was reconnected 10 months after the shunt procedure. Symptoms
improved, but a similar symptom developed one and a half years later. The spinal
catheter was torn at the connection to the shunt valve. The catheter curved to
the left side of the spinal cord and the catheter tip was located around the
right Th12/L1 intervertebral foramen. We continued observations with analgesics,
but symptoms did not subside. The shunt was removed 16 months after symptom
relapse, and symptoms disappeared immediately. Bent insertion of the lumbar
catheter is a potential cause of lower limb neuropathy after LP shunt operation.
Attention must also be paid to the continuity of the catheter in follow-up after
shunt procedures.
PMID- 28490683
TI - [Concomitant Surgery for Symptomatic Severe Carotid Artery Stenosis and Aortic
Valve Stenosis with Contralateral Internal Carotid Artery Occlusion:A Case
Report].
AB - We report a case of concomitant carotid endarterectomy(CEA)and aortic valve
replacement(AVR)for symptomatic severe carotid artery and aortic valve
stenosis(AS). A 77-year-old man, presented to our hospital with AS complicated by
right internal carotid artery(ICA)stenosis and left ICA occlusion, seeking
treatment for AS. He suffered from left hemiparesis, and diffusion-weighted
magnetic resonance imaging(MRI)showed multiple ischemic lesions in the right
cerebral hemisphere. He was admitted to our neurosurgical department and received
treatment for acute cerebral infarction caused by severe right ICA stenosis. The
symptomatic severe right ICA stenosis was an indication for surgical treatment,
but simple carotid revascularization of the stenosed ICA was considered to be
deteriorated the cardiac function due to untreated AS. Thus, we decided to
perform concomitant carotid and valvular surgery. The patient underwent a
combined CEA and AVR procedure with the introduction of an intraoperative intra
aortic balloon pump. His postoperative course was uneventful even 12 months after
the surgery. Management and surgical strategies for patients with concomitant ICA
stenosis and AS continue to be controversial subjects. Combined carotid and
cardiac valve surgery is considered to be effective in such cases, and we discuss
its implications and review of literature.
PMID- 28490684
TI - [Cerebral Venous Sinus Thrombosis Following Cisplatin-Based Chemotherapy for
Testicular Tumor].
AB - A man in his 30s who presented with an enlarged right testicle was diagnosed with
a germ cell tumor via orchiectomy. Adjuvant chemotherapy with cisplatin,
etoposide and bleomycin(BEP)was initiated. He developed a headache 8 days later,
followed by neurological deficits 10 days later. Magnetic resonance
imaging(MRI)and magnetic resonance venography(MRV)showed thrombotic occlusion at
the superior sagittal sinus. Anticoagulant therapy with heparin was initiated.
However, a generalized epileptic seizure occurred 11 days later, and an
antiepileptic drug therapy was initiated. The headache and neurological deficits
gradually improved, and MRI findings showed that the superior sagittal sinus had
re-canalized. The main cause of the sinus thrombosis in this patient was
considered dehydration and cisplatin-induced hypercoagulability. Five courses of
BEP therapy were carried out with care to avoid dehydration. The patient has
remained free of testicular tumor recurrence, metastasis, and cerebral sinus
thrombosis for 2 years. Cisplatin-based chemotherapy is an established risk
factor for venous thromboembolism(VTE), and cerebral sinus thrombosis is a rare
but dangerous complication. Therefore, cerebral sinus thrombosis should be
considered when patients with testicular cancer who undergo cisplatin-based
chemotherapy start to develop neurological symptoms. Clinicians should be aware
of this treatable complication.
PMID- 28490685
TI - [Ruptured C2 Aneurysm of the Internal Carotid Artery with Ipsilateral Unruptured
Giant Internal Carotid Artery Aneurysm:A Case Report].
AB - A giant intracranial internal carotid artery(ICA)aneurysm is difficult to treat.
We encountered a case with an unruptured giant intracranial ICA aneurysm with a
ruptured C2 aneurysm of the ipsilateral ICA. In this case report, we describe how
the treatment and review the literature. A 59-year-old man presented with sudden
onset headache and vomiting. He was diagnosed at a local neurosurgical unit as
having a subarachnoid hemorrhage and admitted to our hospital. Cerebral angiogram
revealed an unruptured giant ICA C3-4 aneurysm with a ruptured aneurysm of the
ipsilateral ICA C2. The ruptured aneurysm had a wide neck and was located in the
medial wall of the ICA C2;it was difficult to perform neck clipping or coil
embolization. We performed a high-flow bypass using a radial artery graft
followed by trapping of the left ICA. Postoperative imaging showed no new
ischemic damage, and the patency of bypass flow was good. The left ophthalmic
artery was perfused from the external carotid artery. Although the patient
experienced incomplete left oculomotor nerve palsy and left lower
quadrantanopsia, his neurological function had recovered within a year, and he
was able to resume his previous work. High-flow bypass with ICA trapping is
effective for ICA giant aneurysm. Attention to postoperative ophthalmic function
and oculomotor symptoms is important.
PMID- 28490686
TI - [A Case of Meralgia Paresthetica Treated with Neurolysis].
AB - A 60-year-old woman presented with a 1-year history of pain and numbness in the
left anterolateral thigh. The symptoms aggravated on walking and standing. Her
visual analogue scale(VAS)score was 7.1/10. Tinel's like sign was positive over
the lateral femoral cutaneous nerve(LFCN), in the inguinal ligament region. LFCN
block at the trigger point, in the inguinal ligament, resulted in relief of the
symptoms and we diagnosed meralgia paresthetica(MP), which is the entrapment
neuropathy of the LFCN. Initially, we performed observation therapy with oral
medication and LFCN blocks. However, these treatments failed to relieve the
symptoms. Therefore, we performed neurolysis with a microscope under local
anesthesia. The symptoms improved immediately after surgery and her VAS score of
thigh symptom improved from 7.1 to 1.9 after 3 months. Conservative and surgical
treatment for MP generally yield good outcome and we should pay attention to the
MP as a differential diagnosis for thigh numbness and pain.
PMID- 28490687
TI - [Association between Glioblastoma with Oligodendroglioma Component and
Subcortical Hemorrhage:A Case Report].
PMID- 28490688
TI - [Pre- and Intra-Operative Supporting Technology for Brain Tumors(7)Surgery for
Cerebellopontine Angle Brain Tumors].
PMID- 28490689
TI - Patient-derived cells modeling pediatric glioma.
PMID- 28490691
TI - The puzzling interplay between p53 and Sp1.
PMID- 28490690
TI - A decline in female baboon hypothalamo-pituitary-adrenal axis activity
anticipates aging.
AB - Stressors that disrupt homeostasis advance aging. Glucocorticoids regulate
multiple processes that determine the aging trajectory. Debate exists regarding
life-course circulating glucocorticoid concentrations. Rodent and nonhuman
primate studies indicate circulating glucocorticoids fall from early life. We
measured fasting morning cortisol in 24 female baboons (6-21 years, human
equivalent ~18-70). We also quantified hypothalamic paraventricular nuclear (PVN)
arginine vasopressin (AVP), corticotropin-releasing hormone, steroid receptors,
and pituitary proopiomelanocortin immunohistochemically in 14 of these females at
6-13 years. We identified significant age-related 1) linear fall in cortisol and
PVN AVP from as early as 6 years; 2) increased PVN glucocorticoid and
mineralocorticoid receptors; 3) increased PVN 11beta-hydroxysteroid dehydrogenase
1 and 2, regulators of local cortisol production, and 4) decreased pituitary
proopiomelanocortin. Our data identify increased age-related negative feedback
and local PVN cortisol production as potential mechanisms decreasing PVN drive to
hypothalamo-pituitary-adrenal axis activity that result in the age-related
circulating cortisol fall. Further studies are needed to determine whether the
cortisol fall 1) causes aging, 2) protects by slowing aging, or 3) is an
epiphenomenon unrelated to aging processes. We conclude that aging processes are
best studied by linear life-course analysis beginning early in life.
PMID- 28490692
TI - [Identification of the interacting proteins with S100A8 or S100A9 by affinity
purification and mass spectrometry].
AB - OBJECTIVE: To identify the interacting proteins with S100A8 or S100A9 in HEK293
cell line by flag-tag affinity purification and liquid chromatography mass
spectrometry/mass spectrometry (LC-MS/MS).? Methods: The p3*Flag-CMV-S100A8 and
p3*Flag-CMV-S100A9 expression vectors were constructed by inserting S100A8 or
S100A9 coding sequence. The recombinant plasmids were then transfected into
HEK293 cells. Affinity purification and LC-MS/MS were applied to identify the
proteins interacting with S100A8 or S100A9. Bioinformatics analysis was used to
seek the gene ontology of the interacting proteins. Co-immunoprecipitation (Co
IP) was applied to confirm the proteins interacted with S100A8 or S100A9.?
Results: Fourteen proteins including pyruvate kinase, muscle (PKM), nucleophosmin
(NPM1) and eukaryotic translation initiation factor 5A (EIF5A), which potentially
interacted with S100A8, were successfully identified by Flag-tag affinity
purification followed by LC-MS/MS analysis. Six proteins, such as tyrosine 3
monooxygenase/tryptophan 5-monooxygenase activation protein epsilon (14-3
3epsilon) and PKM, which potentially interacted with S100A9, were successfully
identified. Gene ontology analysis of the identified proteins suggested that
proteins interacted with S100A8 or S100A9 were involved in several biological
pathways, including canonical glycolysis, positive regulation of NF-kappaB
transcription factor activity, negative regulation of apoptotic process, cell
cell adhesion, etc. Co-IP experiment confirmed that PKM2 can interact with both
S100A8 and S100A9, and 14-3-3epsilon can interact with S100A8.? Conclusion: PKM2
is identified to interact with both S100A8 and S100A9, while 14-3-3epsilon can
interact with S100A9. These results may provide a new clue for the role of S100A8
or S100A9 in the progression of colitis-associated colorectal cancer.
PMID- 28490693
TI - [Comparison of differentiated endothelial cells from the embryonic stem cells
with human umbilical vein endothelial cells].
AB - OBJECTIVE: To compare the differentiated endothelial cells from the embryonic
stem cells in vitro with human umbilical vein endothelial cells (HUVECs).?
Methods: Induction of the stem cells HUES9 to endothelial cells follows 2 steps.
Stem cells were treated with CHIR99021 (10 umol/L) and bone morphogenetic protein
4 (25 ng/mL) for 3 days to keep mesoderm state, then subsequent exposure them to
VEGF165 (200 ng/mL) and Forskolin (2 umol/L) to differentiate into endothelial
cells. The morphology of differentiated endothelial cells were compared with
HUVECs. The surface marker CD144 on differentiated cells and HUVECs were
detected. The capabilities of two types of endothelial cells in migration and
angiogenesis were examined.? Results: The differentiated endothelial cells show
the same morphology with HUVECs. After 6 days of differentiation, the efficiency
reached 73.4%. The positive percentage of CD144 for the differentiated
endothelial cells and HUVECs was 86.6% and 94.4%, respectively. Both of them show
capabilities of migration and angiogenesis, especially when they were treated
with SB431542 to inhibit TGF-beta signal pathway.? Conclusion: The method for
induction of stem cells to endothelial cells is productivity and it can be used
for further study.
PMID- 28490694
TI - [Effect of acupuncture combined with hypothermia on MAPK/ERK pathway and
apoptosis related factors in rats with cerebral ischemia reperfusion injury].
AB - OBJECTIVE: To observe effect of acupuncture combined with hypothermia therapy on
MAPK/ERK pathway and apoptosis related factorsin rats suffered cerebral ischemia
reperfusion and to explore underlying mechanisms.? Methods: Middle cerebral
artery ischemia model were established.Ninety SD rats were randomly assigned into
a blank group, a control group, a model group, an acupuncture group, a mild
hypothermia group, and an acupuncture with hypothermia group. After 72 h
treatment, nerve function defect scores were observed, and infarction area
percent was detected by 2, 3, 5-triphenyl-2H-tetrazolium chloride (TTC) staining;
expressions of Bcl-2 and Bax were examined by immunohistochemistry; apoptotic
cells were detected by TUNEL assay; and expression levels of phospho-mitogen
activated protein kinase(p-MEK2) and phospho-extracellular signal regulated
kinase 1/2 (p-ERK1/2) in the rats' hippocampus ischemic side were determined by
Western blot.? Results: In the rats of the model group, the neural function
defect scores, the infarction area percent, the expression level of Bax, and
apoptotic cells increased, while the level of Bcl-2 decreased significantly. The
level of p-MEK2 and p-ERK1/2 increased obviously compared with the blank and
control groups (P<0.05 or P<0.01). After treatment with acupuncture and
hypothermia, the neural function defect scores, infarction area percent, and the
level of Bax, apoptotic cells and the levels of p-MEK2 and p-ERK1/2 were
significantly decreased, while the level of Bcl-2 in the treatment group was
significantly elevated (P<0.05 or P<0.01) compared with the model group. Compared
with the acupuncture group or the hypothermia group, the neural function defect
scores and the levels of p-MEK2 and p-ERK1/2 in the acupuncture combined with
hypothermia group were significantly reduced (P<0.05 or P<0.01).? Conclusion:
Acupuncture and hypothermia therapy can improve cerebral function, and reduce the
cerebral injury through down-regulation of Bax level, and up-regulation of Bcl-2
level, which is related to reducing the levels of p-MEK2 and p-ERK1/2. The
therapeutic effects on cerebral ischemia reperfusion injury for combination of
acupuncture with hypothermia are better than those with single application of
acupuncture or hypothermia.
PMID- 28490695
TI - [Effect of hydrogen sulfide on inducible nitric oxide synthase in kidneys of Type
1 diabetic rats].
AB - OBJECTIVE: To investigate effects of hydrogen sulfide (H2S) on inducible nitric
oxide synthase (iNOS) in kidneys of Type 1 diabetic rats.? Methods: Thirty-two
male SD rats were randomly divided into four groups: A normal control (NC) group,
a diabetes mellitus (DM) group, a NaHS (NaHS+DM) group, and a NaHS control (NaHS)
group (n=8 per group). Type 1 diabetes was induced by a single intraperitoneal
injection of streptozotocin (55 mg/kg). After successful establishment of models,
the rats in NaHS+DM and NaHS groups were injected with NaHS solution (56
MUmol/kg) intraperitoneally. Eight weeks later, the activities of total nitric
oxide synthase (T-NOS) and iNOS, as well as the level of nitric oxide (NO) were
detected in serum and renal tissues, respectively. The activity of glutathione
peroxidase (GSH-Px) was determined in renal tissues. The ultrastructures of renal
tissues were observed by transmission electron microscope. The protein expression
of iNOS in renal tissues was detected by Western blot.? Results: Compared with
the NC group, there was no significant difference in the various indexes in the
NaHS group (P>0.05). However, in the DM group, the activities of T-NOS and iNOS,
and the level of NO were all increased significantly in serum and renal tissues,
while the activity of GSH-Px was decreased in renal tissues. Under the electronic
microscope, the thickening of the glomerular capillary basement membrane, the
proliferation of mesangial matrix, and the foot fusion were observed. The protein
expression of iNOS was increased obviously in renal tissues in the DM group
(P<0.01). Compared with the DM group, the activities of T-NOS and iNOS and the
level of NO were all decreased in serum and renal tissues, while the activity of
GSH-Px was increased in renal tissues in the NaHS+DM group (P<0.01). The renal
ultrastructural damages were ameliorated obviously. The protein expression of
iNOS was decreased significantly (P<0.01).? Conclusion: H2S exerts a protective
effect on kidney injury in type 1 diabetic rats. The mechanism might be related
to inhibition of iNOS activity and protein expression, in turn leading to
reduction of NO content in renal tissues.
PMID- 28490696
TI - [Diagnostic value of renal phospholipase A2 receptor and serum anti-phospholipase
A2 receptor antibody in membranous nephropathy].
AB - OBJECTIVE: To examine the expression of phospholipase A2 receptor (PLA2R) in
renal tissues and the level of anti-PLA2R antibody in serum in patients with
idiopathic membranous nephropathy (IMN) and secondary membranous nephropathy
(SMN), and to evaluate their diagnostic value in IMN.? Methods: A total of 73
patients, who were diagnosed between May, 2014 and February, 2015 in the
Department of Nephrology of the Second Xiangya Hospital, Central South
University, were divided into three groups: an IMN group (n=48), an SMN group
(n=17) and a minimal change disease group (n=8) according to the renal biopsy.
PLA2R expression in renal tissues and the level of anti-PLA2R antibody in serum
were detected by indirect immunofluorescence technique.? Results: The positive
rate and fluorescence intensity for PLA2R in the renal tissues in the IMN group
were higher than those in the SMN group (91.7% in the IMN group vs 29.4% in the
SMN group, P<0.05), while the positive rate and serum level for anti-PLA2R
antibody in the IMN group were higher than those in the SMN group (85.4% in the
IMN group vs 29.4% in the SMN group, P<0.05); the expression of PLA2R in renal
tissues and the serum level for anti-PLA2R antibody were not detected in the
minimal change disease group. The serum level of anti-PLA2R antibody was
positively correlated with 24 h urine protein (r=0.432, P<0.01) and negatively
correlated with serum albumin (r=-0.307, P<0.05).? Conclusion: The expression of
PLA2R in renal tissues and the serum level of anti-PLA2R antibody might be
potential markers for diagnosis of IMN.
PMID- 28490697
TI - [Effect of left ventricular hypertrophy and deformation on cardiac function in
patients with uremia cardiomyopathy by using quantitative speckle tracking
technology].
AB - OBJECTIVE: To evaluate the effect of left ventricular hypertrophy and deformation
on cardiac function in patients with uremic cardiomyopathy (UCM) by using the
technology of two dimensional speckle tracking imaging (2D-STI).? Methods: A
total of 67 UCM patients were randomly divided into the normal cardiac function
group (subgroup A, 32 cases) and the abnormal cardiac function group (subgroup B,
35 cases) according to the New York Heart Association points (NYHA-P). A total of
30 healthy subjetcs served as the control group. Parameters including left
ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), left
ventricular spherical index (LVSI), left ventricular myocardial mean radial
strain (MRS), mean radial strain rate (MRSR), mean longitudinal strain (MLS),
local systolic twist angle (STA), and mitral annulus maximum displacement (TMAD)
were detected.? Results: MLS, MRS, MRSR, LVSI, STA and TMAD in the Group A and
Group B were lower than that in the control group (P<0.05), and LVMI in the Group
A and Group B was increased than those in the control group (P<0.05); LVEF, MLS,
MRS, MRSR, LVSI and STA in the Group B was decreased than that in the Group A
(P<0.05). MLS in the Group A and B were positively correlated with LVEF and LVSI,
but negatively correlated with LVMI. Using the point of 14.10% for MLS to
evaluate UCM patients with NYHA-P>4 points, the sensitivity, the specificity and
Yuedden index were 90.5%, 71% and 0.585, respectively. STA in UCM patients were
lower than that in the control (P<0.05).? Conclusion: 2D-STI possesses a unique
advantage in detecting left ventricular strain and strain rate on left
ventricular regional function in UCM with left ventricular hypertrophy and
ventricular deformation. There is no direct correlation between the left
ventricular hypertrophy and ventricular deformation, but the ventricular
hypertrophy and deformation are correlated with regional cardiac function and
clinical cardiac function. Left ventricular regional dysfunction may occur before
cardiac hypertrophy and deformation.
PMID- 28490698
TI - [Diagnosis and differential diagnosis for solitary fibrous tumor in the abdomen
and pelvis by CT].
AB - OBJECTIVE: To study the CT features for solitary fibrous tumor (SFT) in the
abdomen and pelvis and to improve the diagnostic accuracy.? Methods: Fourteen
patients with SFT were collected in our hospital from January, 2011 to December,
2015. Characteristic of images were analyzed and compared for 10 SFT, which
located outside the abdominal organs with extragastrointestinal stromal tumors
(EGIST), leiomyosarcoma, and schwannoma.? Results: Necrosis and cystic formation
were frequently present in SFT in the abdomen and pelvis. CE-CT showed serpentine
vessels along the periphery, while pattern of enhancement was map-like
inhomogeneous progressive. Comparing with the EGIST or schwannoma, the difference
of CT value in non-contrast and the arterial phase were statistically significant
(P<0.05). The numbers of peritumoral circuity vessel were significantly different
between SFT and EGIST (chi2=18.27, P<0.008) or between SFT and schwannoma
(chi2=19.25, P<0.008). Comparing with the leiomyosarcoma or schwannoma, SFT
located outside the abdominal organs. We found that tumor necrosis rate was
significantly different between SFT and leiomyoscarcoma (chi2=8.00, P<0.008).?
Conclusion: SFT in the abdomen and pelvis show certain CT characteristics. The CT
value in non-contrast and at the arterial phase, tumor necrosis rate, and
serpentine vessels along the periphery were pivotal in differentiating SFT from
leiomyosarcoma, EGIST and schwannoma.
PMID- 28490699
TI - [Effect of tumor volume on pulmonary dose-volume parameter by intensity-modulated
radiation therapy in non-small cell lung cancer].
AB - OBJECTIVE: To explore the effectof tumor volume on pulmonary dose-volume
parameters by intensity-modulated radiation therapy (IMRT) in non-small cell lung
cancer (NSCLC), and to provide a basis for pulmonary dose parameters in IMRT
treatment.? Methods: A total of 204 patients with NSCLC received IMRT were
retrospectively analyzed from June, 2009 to October, 2013. The prescribed dose of
planning target volume (PTV) for primary tumor was 60-66Gy (2.00-2.25 Gy, 27-33
times in all). The fractional volume percent of the lung received a dose >5 or 20
Gy (V5, V20), and absolute volume of lung received a dose <5 Gy (AVS5).The mean
lung dose (MLD) in normal tissues were analyzed. Regression model curve was used
to analyze them along with the change of primary tumor volume.? Results: With the
increase in lung tumor volume, the V5, V20 and MLD presented quadratic equation
curve, and AVS5 presented logarithmic equation. When the tumor volume, less than
a certain value (294.6, 283.2, 304.9 cm3, respectively), the V5, V20 and MLD
increased with tumor size and presented an increased quadratic curve; when the
tumor volume was higher than a certain value (294.6, 283.2, 304.9 cm3
respectively), the V5, V20 and MLD was declined. The AVS5 was declined in a
logarithmic curve along with the increase of tumor volume.? Conclusion: With the
increase in lung tumor volume, the change in rule of V5, V20, MLD and AVS5 is not
completely equivalent. When the tumor volume exceeds a certain boundary value
(about 300 cubic centimeter), the corresponding tumor diameter is about 7-8 cm.
In addition to the focus on pulmonary V5, V20 and MLD, we should also pay more
attention to AVS5 restrictions in establishment of IMRT in NSCLC.
PMID- 28490700
TI - [Role of TGF-beta1 in multi-drug resistance in small cell lung cancer and its
clinical significance].
AB - OBJECTIVE: To investigate the role of transforming growth factor beta1 (TGF
beta1) in multi-drug resistance in small cell lung cancer and its clinical
significance.? Methods: The mRNA and protein expressions of TGF-beta1 in H69 and
H69AR cells were detected by real-time PCR and Western blot, respectively. After
silence of TGF-beta1, the sensitivity of H69AR to drugs was detected by CCK8
assay. The expressions of TGF-beta1 in lung cancer and paracarcinoma tissues were
examined by QRT-PCR and immunohistochemistry. The relationship of TGF-beta1
expression with clinical pathological features and prognosis of patients was
studied.? Results: Compared to H69, the mRNA and protein expressions of TGF-beta1
in H69AR cells were significantly increased by (5.93+/-0.47) and (8.49+/-1.92)
folds, respectively (P<0.01). Transfection of TGF-beta1 siRNA resulted in a
decrease of TGF-beta1 expression by 70.432% in H69AR cells (F=21.20, P<0.01) and
an increase insensitivity to chemotherapeutic agents of H69AR cells (t=4.576,
P<0.05). Compare with the paracarcinoma tissues, the expression of TGF-beta1 was
significantly increased in small cell lung cancer tissues (t=13.925, P<0.01),
which was closely related with clinical stage, chemosensitivity and overall
survival (all P<0.05), but not related with gender, age (both P>0.05).?
Conclusion: TGF-beta1 is involved in the regulation of small cell lung cancer
multidrug resistance, which may be a potential marker to evaluate the
chemosensitivity and clinical prognostic for small cell lung cancer.
PMID- 28490701
TI - [AdeABC efflux pump and resistance of Acinetobacter baumannii against
carbapenem].
AB - OBJECTIVE: To investigate relationship between AdeABC efflux pump and resistance
of Acinetobacter baumannii against carbapenem.? Methods: Carbapenem-resistant
strains were acquired from multistep selection resistance test by meropenem in
vitro. The quantitation test for sensitivities of strains before and after
induction was determined by the E-test, and carbonylcyanide-m
chlorophenylhydrazone (CCCP) inhibition test was used to screen efflux pump. PCR,
sequencing analysis, or real-time PCR was used to analyze the changes of
regulatory genes adeR and adeS of the AdeABC efflux pump system, or expressions
of adeA, adeB, adeR, and adeS in the strains before and after induction,
respectively.? Results: The minimal inhibitory concentrations (MICs) of meropenem
were at 0.38 MUg/mL and 0.25 MUg/mL in parental sensitive strain S25595 and
S7257, respectively, and the MICs of meropenem for both S25595 and S7257 after
induction were more than 32 MUg/mL. Compared with parental sensitive strains, the
expression level of adeA, adeB, adeR, and adeS mRNA were elevated from 2.45 to
9.44 times, but there were no gene mutations or insertion sequences in the
regulatory gene adeS and adeR.? Conclusion: High expression of the AdeABC efflux
pump system in Acinetobacter baumannii is closely associated with meropenem
resistance. The upregulation of adeA and adeB expression is not due to gene
mutations in the regulatory gene adeS and adeR and other mechanisms might account
for it.
PMID- 28490702
TI - [Status for self-medication based on bibliometric study in China].
AB - OBJECTIVE: To figure out problems through analyzing the status for self
medication in China and to provide references for further research.? Methods:
Papers related to self-medication were collected from Chinese journal net
database, Wanfang database, VIP database and China biomedical literature database
(CBMDisc). A literature metrology analysis was carried out by NoteExpress 2.0 and
Excel.? Results: A total of 161 papers were included in this study, while 33
papers belong to Hubei and Jiangsu Province, accounting for 20.50% of the total
amount of the papers. 22 papers were from journals as follows: China Pharmacy,
Medicine and Society and Chinese Journal of Pharmacoepidemiology, accounting for
13.67% of the total papers. 118 papers belong to research and experience discuss,
accounting for 73.29% of all. The cooperation degree was 2.37, and 28 papers were
funded. Domestic research reflected the current status of self-medication in our
country. Although self-medication brought convenience for residents and reduce
the burden on health system, it also brought a series of safety problems.?
Conclusion: Self-medication gradually catches the attention of the researchers.
Some researchers have paid attention to self medication, but the evidence is at a
low level. Researchers should strengthen cooperation with interagency and carry
out experimental study to promote further development for self-medication.
PMID- 28490703
TI - [Construction of a psychological aging scale for healthy people].
AB - OBJECTIVE: To construct a psychological aging scale, and to provide a tool and
indexes for scientific evaluation on aging.? Methods: The age-related
psychological items were collected through literature screening and expert
interview. The importance, feasibilityand the degree of authority for the
psychological index system were graded by two rounds of Delphi method. Using
analytic hierarchy process, the weight of dimensions and items were determined.
The analysis for internal consistency reliability, correlation and exploratory
factor was performed to evaluate the reliability and validity of the scales.?
Results: By two rounds of Delphi method, 17 experts offered the results as
follows: the coefficient of expert authorities was 0.88+/-0.06, the coordination
coefficients for the importance and feasibility in second round were 0.456
(P<0.01) and 0.666 (P<0.01), respectively. The consistency was good. The
psychological aging scale for healthy people included 4 dimensions as follows:
cognitive function, emotion, personality and motivation. The weight coefficients
for the 4 dimensions were 0.338, 0.250, 0.166 and 0.258, respectively. The
Cronbach's alpha coefficient for the scale was 0.822, the reliability was 0.817,
the content validity index (CVI) was 0.847, and the cumulative contribution rate
for the 5 factors was51.42%.? Conclusion: The psychological aging scale is
satisfied, which can provide reference for the evaluation for aging. The
indicators were representative and well-recognized.
PMID- 28490704
TI - [Establishement for regional pelvic trauma database in Hunan Province].
AB - OBJECTIVE: To establish a database for pelvic trauma in Hunan Province, and to
start the work of multicenter pelvic trauma registry.? Methods: To establish the
database, literatures relevant to pelvic trauma were screened, the experiences
from the established trauma database in China and abroad were learned, and the
actual situations for pelvic trauma rescue in Hunan Province were considered. The
database for pelvic trauma was established based on the PostgreSQL and the
advanced programming language Java 1.6.? Results: The complex procedure for
pelvic trauma rescue was described structurally. The contents for the database
included general patient information, injurious condition, prehospital rescue,
conditions in admission, treatment in hospital, status on discharge, diagnosis,
classification, complication, trauma scoring and therapeutic effect. The database
can be accessed through the internet by browser/servicer. The functions for the
database include patient information management, data export, history query,
progress report, video-image management and personal information management.?
Conclusion: The database with whole life cycle pelvic trauma is successfully
established for the first time in China. It is scientific, functional, practical,
and user-friendly.
PMID- 28490705
TI - [Spatial distribution and clustering in birth defects from 2010 to 2013 in
Shaanxi Province].
AB - OBJECTIVE: To explore the spatial distribution and clustering in birth defects
from 2010 to 2013 in Shaanxi Province.? Methods: Spatial distribution was used to
describe the birth defects, while ordinary Kriging method was used to predict the
status of birth defects in Shaanxi province. The spatial characteristics for the
birth defects at the county/district level were analyzed by spatial
autocorrelation.? Results: The overall incidence of birth defects was 219.196/10
000; Birth defect did not appear to be a random distribution but show a
significant spatial aggregation. Spatial interpolation predicted the geographic
distribution for occurrence of birth defects in Shaanxi Province. Local
autocorrelation analysis showed nine "hot spot areas" for birth defects, such as
Qian County, Liquan County, Yongshou County, Bin County, Fufeng County, Jingyang
County, Chunhua County, Wugong County and Xingping City, and seven "cold spot
areas" including Jia County, Yuyang District, Mizhi County, Suide County, Wubu
County, Qingjian County and Zizhou District.? Conclusion: There are spatial
clustering in birth defects from 2010 to 2013 in Shaanxi Province. Spatial
interpolation and spatial autocorrelation can be used to predict the spatial
features of birth defects in the whole province and provide evidence for the
further intervention.
PMID- 28490706
TI - [Progress of the application of stem cell therapy for end-stage liver disease].
AB - Many risk factors lead to hypohepatia and hepatic failure, causing people
suffering from end-stage liver disease. The conventional treatment for end-stage
liver disease is not good enough. Orthotopic liver transplantation is effective.
However, the high cost, lack of liver source, immune rejection and other factors
limit the large-scale clinical application. Thus, cell therapy is a good option.
Studies on common cell sources for the treatment of liver disease and the
induction of hepatocytes by embryonic stem cells or pluripotent stem cells have
made progress. With the development of stem cell technology, cell transplantation
has become a new option, which brings hope to people with end-stage liver
diseasetransplantation has become a new option. It brings hope to people with end
stage liver disease.
PMID- 28490707
TI - [Effect of NF-kappaB on the pathogenic course of non-alcoholic fatty liver
disease].
AB - With the economic growth and better standards of living, the prevalence of non
alcoholic fatty liver disease (NAFLD) is expected to increase dramatically
worldwide. NAFLD is a common chronic inflammation disease. NF-kappaB is a
transcription factor that plays crucial roles in inflammation, immunity, cell
proliferation and apoptosis. It can facilitate the occurrence and development of
NAFLD, and the underlying mechanisms are related to insulin resistance, oxidative
stress, alteration of intestinal flora, activation of renin angiotensin system,
etc.
PMID- 28490708
TI - [Advance in glutathione S-transferase kappa 1].
AB - Glutathione S-transferase kappa 1 (GSTK1) is a key regulator for adiponectin
secretion and multimerization. In Caenorhabditis elegans, GSTK1 is involved in
energy production and lipid metabolism. Meanwhile, the GSTK1 level is negatively
correlated with obesity. It may alleviate the endoplasmic reticulum stress
mediated downregulation of adiponectin. Moreover, a polymorphism in human GSTK1
promoter is related with insulin secretion and fat deposition. Therefore, GSTK1
might be a novel target for the treatment of insulin resistance and the relevant
metabolic diseases.
PMID- 28490709
TI - [Research progress in mechanisms and clinical application for blonanserin and
lurasidone in improving cognitive function of schizophrenia].
AB - Cognition deficit is one of the most common symptoms of schizophrenia, including
abstract thinking and memory, and attention deficits. Previous studies have
suggested that the improvement of cognition is very important for the recovery of
disease and social function for the patients. Recent studies indicated that two
new atypical antipsychotics, blonanserin and lurasidone, are expected to improve
the cognitive impairment in patients with schizophrenia. This review introduces
pathogenesis of cognitive impairment in schizophrenia, mechanisms of blonanserin
and lurasidone in the improvement of cognitive impairment and progress in their
clinical application for schizophrenia. We hope that this review could guide
clinical use of antipsychotics and provide new directions for future studies.
PMID- 28490710
TI - [Small fugal enteritis manifestation with intestinal obstruction and
hematochezia: a case report].
AB - Fungal enteritis was rarely reported. A case of fungal enteritis manifestation
with jejunum multiple ulcers and obstruction was treated by Department of
Gastroenterology, Third Xiangya Hospital, Central South University. After
antifungal treatment, the clinical symptoms were relieved, and the ulcers in
jejunal and upper gastrointestinal tract were healed completely. Clinical
manifestation for small fungal enteritis is special, and the small intestine
ulcer is easily to be misdiagnosed. It is helpful to prevent the misdiagnose for
small fungal enteritis if we can tell the clinical features for this disease.
PMID- 28490711
TI - Purification, Crystallization and X-ray Diffraction Study of the C-terminal
Domain of Human Herpesvirus 6A Immediate Early Protein 2.
AB - Human herpesvirus 6A (HHV-6A) starts its replication cycle following the action
of immediate early proteins that transactivate viral promoters. Immediate early
protein 2 (IE2) of HHV-6A is a 1500 amino acid polypeptide with a C-terminal
region that is conserved among beta-herpesvirus subfamily members. In this study,
a structural domain in the homologous C-terminal region was subjected to
secondary structure prediction, and residues 1324-1500 were subsequently
designated as the C-terminal domain of IE2 (IE2-CTD). The gene fragment encoding
IE2-CTD was inserted into an E. coli expression vector and expressed as a fusion
protein with maltose binding protein (MBP) at the N-terminus. IE2-CTD has a
theoretical isoelectric point (pI) of 9.29, and strong cation exchange column
chromatography was effective for purification. Needle-shaped crystals of IE2-CTD
were obtained using the sitting-drop vapour diffusion method, and larger
selenomethionine-labelled crystals of space group P21 diffracted X-rays to 2.5 A
resolution using synchrotron radiation. Data were collected at the selenium
absorption peak wavelength for experimental phasing by the single anomalous
dispersion method. The resulting electron density map clearly shows the protein
backbone, and full structural determination and refinement are in progress.
PMID- 28490712
TI - Application of Physiologically-Based Pharmacokinetic Modeling for the Prediction
of Tofacitinib Exposure in Japanese.
AB - Tofacitinib (3-[(3R,4R)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4
yl)amino]piperidin-1-yl]-3 -oxopropanenitrile) is an oral Janus kinase inhibitor
that is approved in countries including Japan and the United States for the
treatment of rheumatoid arthritis, and is being developed across the globe for
the treatment of inflammatory diseases. In the present study, a physiologically
based pharmacokinetic model was applied to compare the pharmacokinetics of
tofacitinib in Japanese and Caucasians to assess the potential impact of
ethnicity on the dosing regimen in the two populations. Simulated plasma
concentration profiles and pharmacokinetic parameters, i.e. maximum concentration
and area under plasma concentration-time curve, in Japanese and Caucasian
populations after single or multiple doses of 1 to 30 mg tofacitinib were in
agreement with clinically observed data. The similarity in simulated exposure
between Japanese and Caucasian populations supports the currently approved dosing
regimen in Japan and the United States, where there is no recommendation for dose
adjustment according to race. Simulated results for single (1 to 100 mg) or
multiple doses (5 mg twice daily) of tofacitinib in extensive and poor
metabolizers of CYP2C19, an enzyme which has been shown to contribute in part to
tofacitinib elimination and is known to exhibit higher frequency in Japanese
compared to Caucasians, were also in support of no recommendation for dose
adjustment in CYP2C19 poor metabolizers. This study demonstrated a successful
application of physiologically-based pharmacokinetic modeling in evaluating
ethnic sensitivity in pharmacokinetics at early stages of development, presenting
its potential value as an efficient and scientific method for optimal dose
setting in the Japanese population.
PMID- 28490713
TI - Phospholipase D is Dispensable for Epidermal Growth Factor-Induced Chemotaxis.
AB - alpha-Synuclein (alpha-Syn) is implicated in several neurodegenerative disorders,
including Parkinson's disease, known collectively as the synucleinopathies. alpha
Syn is known to be secreted from the cells and may contribute to the progression
of the disease. Although extracellular alpha-Syn is shown to impair platelet
derived growth factor-induced chemotaxis, molecular mechanism of alpha-Syn
induced motility failure remains elusive. Here we have aimed at phospholipase D
(PLD) as a potential target for alpha-Syn and examined the involvement of this
enzyme in alpha-Syn action. Indeed, extracellular alpha-Syn caused inhibition of
agonist-induced PLD activation. However, inhibition of hydrolytic activity of PLD
by 1-butanol treatment showed little or no effect on agonist-induced chemotaxis.
These results suggest that some signaling pathways other than PLD may be involved
in alpha-Syn-induced inhibition of chemotaxis.
PMID- 28490714
TI - The seroprevalence of Bartonella henselae in healthy adults in Korea.
AB - BACKGROUND/AIMS: Cat-scratch disease (CSD), caused by Bartonella henselae is one
of the most common zoonosis. However, only several cases of B. henselae infection
have been reported in Korea. This study investigated the seroprevalence of B.
henselae in healthy adults and related risk factors. METHODS: Serum samples from
300 healthy participants were analyzed using an immunoglobulin G immunof
luorescence assay (IFA) for B. henselae isolated in Korea. Surveys on the risk
factors for B. henselae infection were conducted simultaneously. RESULTS: Of the
participants, 47.7% and 15.0% raised dogs and cats, respectively. The overall
seroprevalence of B. henselae was 15.0% (IFA titer >= 1:64). Participants who had
raised cats showed 22.2% seropositivity against B. henselae, and those with no
experience with cats showed 13.7% seroprevalence (p = 0.17). Participants who had
cats as pets or been scratched by cats, showed 9.8% seropositivity against B.
henselae (IFA titer >= 1:256). However, those who had not raised or been
scratched by a cat showed 2.0% seropositivity (p = 0.015). CONCLUSIONS: In Korea,
the seroprevalence of B. henselae is higher than expected, suggesting that
Bartonella infection due to B. henselae is not uncommon. Cats are proposed to
play a more important role than dogs in transmission of CSD.
PMID- 28490715
TI - Approach to cytomegalovirus infections in patients with ulcerative colitis.
AB - Cytomegalovirus (CMV) reactivation is common in patients with severe ulcerative
colitis (UC), and may ref lect exacerbation of mucosal inf lammation and/or
administration of immunosuppressants. The question of whether CMV is an active
pathogen or 'an innocent bystander' in the exacerbation of UC remains
controversial. Patients with UC exacerbated by reactivated CMV experience worse
prognoses than those without CMV reactivation and antiviral therapy significantly
reduces the need for colectomy in patients with severe UC and high-grade CMV
infection, indicating that CMV plays a role in UC prognosis. Therefore, the CMV
status of patients on immunosuppressants, particularly those with steroid
refractory or -dependent UC, should be tested. When CMV is detected, be performed
based on should adequate treatment the extent of the viral load and the presence
of certain clinical features including a large ulcer. Anti-tumor necrosis factor
agents may be useful for treating CMV colitis complicating UC.
PMID- 28490716
TI - Comment on "Hypogonadotrophic hypogonadism due to a mutation in the luteinizing
hormone beta-subunit gene".
PMID- 28490717
TI - Erratum: Two-year clinical outcomes in stable angina and acute coronary syndrome
after percutaneous coronary intervention of left main coronary artery disease.
AB - [This corrects the article on p. 1084 in vol. 31, PMID: 27756119.].
PMID- 28490718
TI - Comment on "New therapeutic agents in diabetic nephropathy".
PMID- 28490719
TI - Realities of KRAS-mutated non-small cell lung cancer.
PMID- 28490720
TI - Oxidative stress: link between hypertension and diabetes.
PMID- 28490721
TI - Response to comment on "New therapeutic agents in diabetic nephropathy".
PMID- 28490722
TI - Response to comment on "Hypogonadotrophic hypogonadism due to a mutation in the
luteinizing hormone beta-subunit gene".
PMID- 28490723
TI - Incidence and clinical characteristics of gastroenteropancreatic neuroendocrine
tumor in Korea: a single-center experience.
AB - BACKGROUND/AIMS: Neuroendocrine tumors (NETs) may originate from heterogeneous
neuroendocrine cells. The incidence is increasing worldwide, and World Health
Organization (WHO) updated its classification in 2010. We investigated clinical
characteristics of gastroenteropancreatic NETs in a single center. METHODS:
Clinicopathologic characteristics of patients with pathologically confirmed
gastroenteropancreatic NET in Seoul St. Mary Hospital from March 2009 to August
2011 were retrospectively analyzed. The grade and stage were determined according
to WHO 2010 classification and TNM Staging System for Neuroendocrine Tumors (7th
ed., 2010) of American Joint Committee on Cancer. RESULTS: One hundred and twenty
five patients (median age, 50; male, 61.3%) were analyzed. Among 100,000 patients
who visited the hospital, incidence was 24.1. Only two patients (1.6%) had a
functional NET. The rectum (n = 99, 79.8%) was most common primary site and found
in early stage. The prevalence by stages was 84.7% stage I, 8.9% stage IV, 4.8%
stage II, and 1.6% stage III. The pathology grading was 74.5% grade 1, 12.7%
grade 2, and 12.7% grade 3. Tumor stage correlated positively with pathologic
grade (Spearman's rank correlation coefficient, 0.644). CONCLUSIONS: Wide range
of clinicopathological features of Korean gastroenteropancreatic NETs were
demonstrated using WHO 2010 classification. Rectal NET was most frequent and
found in early stage.
PMID- 28490724
TI - Infection in systemic lupus erythematosus, similarities, and differences with
lupus flare.
AB - Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with diverse
manifestations, and its pathogenesis is unclear and complicated. Infection and
SLE are similar in that they both cause inf lammatory reactions in the immune
system; however, one functions to protect the body, whereas the other is
activated to damage the body. Infection is known as one of the common trigger
factors for SLE; there are a number of reports on infectious agents that provoke
autoimmune response. Several viruses, bacteria, and protozoa were revealed to
cause immune dysfunction by molecular mimicry, epitope spreading, and bystander
activation. In contrast, certain pathogens were revealed to protect from immune
dysregulation. Infection can be threatening to patients with SLE who have a
compromised immune system, and it is regarded as one of the common causes of
mortality in SLE. A clinical distinction between infection and lupus f lare up is
required when patients with SLE present fevers. With a close-up assessment of
symptoms and physical examination, C-reactive protein and disease activity
markers play a major role in differentiating the different disease conditions.
Vaccination is necessary because protection against infection is important in
patients with SLE.
PMID- 28490725
TI - Effects of valsartan and amlodipine on oxidative stress in type 2 diabetic
patients with hypertension: a randomized, multicenter study.
AB - BACKGROUND/AIMS: Oxidative stress plays an important role in the pathogenesis and
progression of diabetic complications and antagonists of renin-angiotensin system
and amlodipine have been reported previously to reduce oxidative stress. In this
study, we compared the changes in oxidative stress markers after valsartan and
amlodipine treatment in type 2 diabetic patients with hypertension and compared
the changes in metabolic parameters. METHODS: Type 2 diabetic subjects with
hypertension 30 to 80 years of age who were not taking antihypertensive drugs
were randomized into either valsartan (n = 33) or amlodipine (n = 35) groups and
treated for 24 weeks. We measured serum nitrotyrosine levels as an oxidative
stress marker. Metabolic parameters including serum glucose, insulin, lipid
profile, and urine albumin and creatinine were also measured. RESULTS: After 24
weeks of valsartan or amlodipine treatment, systolic and diastolic blood pressure
decreased, with no significant difference between the groups. Both groups showed
a decrease in serum nitrotyrosine (7.74 +/- 7.30 nmol/L vs. 3.95 +/- 4.07 nmol/L
in the valsartan group and 8.37 +/- 8.75 nmol/L vs. 2.68 +/- 2.23 nmol/L in the
amlodipine group) with no significant difference between the groups. Other
parameters including glucose, lipid profile, albumin-to-creatinine ratio, and
homeostasis model assessment of insulin resistance showed no significant
differences before and after treatment in either group. CONCLUSIONS: Valsartan
and amlodipine reduced the oxidative stress marker in type 2 diabetic patients
with hypertension.
PMID- 28490726
TI - Plasma Long Noncoding RNA Urothelial Carcinoma Associated 1 Predicts Poor
Prognosis in Chronic Heart Failure Patients.
AB - BACKGROUND Chronic heart failure (CHF) is a leading cause of death worldwide. A
long noncoding RNA (lncRNA) named urothelial carcinoma associated 1 (UCA1) is
important in multiple diseases. However, the role of UCA1 in CHF is still
unknown. Our study investigated whether UCA1 could be applied as an ideal marker
to diagnose and evaluate prognosis in CHF. MATERIAL AND METHODS Total plasma RNA
was extracted from 67 CHF patients and 67 controls. Quantitative real-time
polymerase chain reaction was used to determine the plasma level of UCA1.
Correlations between UCA1 and clinical parameters were analyzed by Pearson
correlation. Receiver operating characteristic curves (ROC) were obtained to
analyze the predictive power of UCA1 and BNP for CHF. Kaplan-Meier survival
curves were used to evaluate prognosis of CHF within 1 year. RESULTS There was no
significant difference in elementary data between CHF and controls. Plasma UCA1
was much higher in CHF patients compared with controls. Plasma UCA1 was
positively and negatively correlated with brain natriuretic peptide (BNP) and
left ventricle ejection fraction (LVEF), respectively. Plasma UCA1 diagnosed CHF
with a diagnostic power of 0.89 and a sensitivity and specificity of 100% [95% CI
(0.9464-1)] and 76.12% [95%CI (0.6414-0.8569)] (P<0.05), respectively. CHF
patients with higher plasma UCA1 had a lower survival rate than those with a
lower level, and survival rate predicted by UCA1 had a similar tendency with BNP.
However, there was no significant difference between these 2 markers in
predicting the prognosis of CHF (P>0.05). CONCLUSIONS Plasma UCA1 might be an
excellent indicator to diagnose CHF and it might predict poor outcomes of CHF.
PMID- 28490727
TI - Syringocystadenoma Papilliferum of the External Auditory Canal.
AB - BACKGROUND Ceruminous glands are modified apocrine glands, situated in the
external auditory canal, that, together with sebaceous glands, produce cerumen,
better known as ear wax. The neoplastic transformation of these structures is
very rare and there have been few cases reported in the literature. CASE REPORT
Syringocystadenoma papilliferum is one of the rarest tumors among benign tumors
arising from the ceruminous glands. We here report the case of a 72-year-old man
with a lesion histologically documented as a syringocystadenoma papilliferum and
we review the literature, focusing our attention on clinical features and
treatment options of benign glandular tumors arising from the external auditory
canal. CONCLUSIONS Syringocystadenoma papilliferum is a rare benign tumor of the
ceruminous glands of the external ear canal. Excision biopsy is mandatory for the
diagnosis and is the best treatment.
PMID- 28490728
TI - Bright nanoscale source of deterministic entangled photon pairs violating Bell's
inequality.
AB - Global, secure quantum channels will require efficient distribution of entangled
photons. Long distance, low-loss interconnects can only be realized using photons
as quantum information carriers. However, a quantum light source combining both
high qubit fidelity and on-demand bright emission has proven elusive. Here, we
show a bright photonic nanostructure generating polarization-entangled photon
pairs that strongly violates Bell's inequality. A highly symmetric InAsP quantum
dot generating entangled photons is encapsulated in a tapered nanowire waveguide
to ensure directional emission and efficient light extraction. We collect ~200
kHz entangled photon pairs at the first lens under 80 MHz pulsed excitation,
which is a 20 times enhancement as compared to a bare quantum dot without a
photonic nanostructure. The performed Bell test using the Clauser-Horne-Shimony
Holt inequality reveals a clear violation (S CHSH > 2) by up to 9.3 standard
deviations. By using a novel quasi-resonant excitation scheme at the wurtzite InP
nanowire resonance to reduce multi-photon emission, the entanglement fidelity (F
= 0.817 +/- 0.002) is further enhanced without temporal post-selection, allowing
for the violation of Bell's inequality in the rectilinear-circular basis by 25
standard deviations. Our results on nanowire-based quantum light sources
highlight their potential application in secure data communication utilizing
measurement-device-independent quantum key distribution and quantum repeater
protocols.
PMID- 28490729
TI - A comparative multi-parametric in vitro model identifies the power of test
conditions to predict the fibrotic tendency of a biomaterial.
AB - Despite growing effort to advance materials towards a low fibrotic progression,
all implants elicit adverse tissue responses. Pre-clinical biomaterial assessment
relies on animals testing, which can be complemented by in vitro tests to address
the Russell and Burch's 3R aspect of reducing animal burden. However, a poor
correlation between in vitro and in vivo biomaterial assessments confirms a need
for suitable in vitro biomaterial tests. The aim of the study was to identify a
test setting, which is predictive and might be time- and cost-efficient. We
demonstrated how sensitive in vitro biomaterial assessment based on human primary
macrophages depends on test conditions. Moreover, possible clinical scenarios
such as lipopolysaccharide contamination, contact to autologous blood plasma, and
presence of IL-4 in an immune niche influence the outcome of a biomaterial
ranking. Nevertheless, by using glass, titanium, polytetrafluorethylene,
silicone, and polyethylene representing a specific material-induced fibrotic
response and by comparison to literature data, we were able to identify a test
condition that provides a high correlation to state-of-the-art in vivo studies.
Most important, biomaterial ranking obtained under native plasma test conditions
showed a high predictive accuracy compared to in vivo assessments, strengthening
a biomimetic three-dimensional in vitro test platform.
PMID- 28490731
TI - The intestinal tuft cell nanostructure in 3D.
AB - Once referred to as "peculiar," tuft cells are enigmatic epithelial cells. Here,
we reasoned that future functional studies could be derived from a complete
account of the tuft cell ultrastructure. We identified and documented the
volumetric ultrastructure at nanometer resolution (4-5 nm/pixel) of specific
intestinal tuft cells. The techniques used were Serial Block-Face (SBF) and
Automated Tape-collecting Ultra-Microtome (ATUM) Scanning Electron Microscopy
(SEM). Our results exposed a short (~15 um) basal cytoplasmic process devoid of
secretory vesicles. Volume rendering of serial sections unveiled several thin
cytospinules (~1 um). These cytospinules project from the tuft cell into the
nuclei of neighboring epithelial cells. Volume rendering also revealed within the
tuft cell an elegant network of interconnected tubules. The network forms a
passage from the base of the microvilli to the rough endoplasmic reticulum. Based
on their location and microanatomy, the tuft cells' cytospinules, and tubular
network, might facilitate the exchange of molecular cargo with nuclei of
neighboring cells, and the gut lumen.
PMID- 28490730
TI - Multi-pass transmission electron microscopy.
AB - Feynman once asked physicists to build better electron microscopes to be able to
watch biology at work. While electron microscopes can now provide atomic
resolution, electron beam induced specimen damage precludes high resolution
imaging of sensitive materials, such as single proteins or polymers. Here, we use
simulations to show that an electron microscope based on a multi-pass measurement
protocol enables imaging of single proteins, without averaging structures over
multiple images. While we demonstrate the method for particular imaging targets,
the approach is broadly applicable and is expected to improve resolution and
sensitivity for a range of electron microscopy imaging modalities, including, for
example, scanning and spectroscopic techniques. The approach implements a quantum
mechanically optimal strategy which under idealized conditions can be considered
interaction-free.
PMID- 28490732
TI - Confocal imaging of single BaTiO3 nanoparticles by two-photon photothermal
microscopy.
AB - We report on the development of a nonlinear optical microscopic technique based
on two-photon absorption induced photothermal effect capable of detecting
individual nonfluorescent nanoparticles with high sensitivity. The method which
is inherently confocal makes use of near infrared excitation at high repetition
rates and would be of interest in deep tissue imaging. We demonstrate the
applicability of the technique by imaging single BaTiO3 nanoparticles, a
potential biomolecular label having high photostability, in a scattering
environment at fast time scales with a pixel dwell time of 80 MUs.
PMID- 28490733
TI - Pharmacometabolomics for predicting variable busulfan exposure in paediatric
haematopoietic stem cell transplantation patients.
AB - Owing to its narrow therapeutic range and high pharmacokinetic variability,
optimal dosing for busulfan is important to minimise overexposure-related
systemic toxicity and underexposure-related graft failure. Using global
metabolomics, we investigated biomarkers for predicting busulfan exposure. We
analysed urine samples obtained before busulfan administration from 59 paediatric
patients divided into 3 groups classified by area under the busulfan
concentration-time curve (AUC), i.e., low-, medium-, and high-AUC groups. In the
high-AUC group, deferoxamine metabolites were detected. Phenylacetylglutamine and
two acylcarnitines were significantly lower in the high-AUC group than in the low
AUC group. Deferoxamine, an iron-chelating agent that lowers serum ferritin
levels, was detected in the high-AUC group, indicating that those patients had
high ferritin levels. Therefore, in a retrospective study of 130 paediatric
patients, we confirmed our hypothesis that busulfan clearance (dose/AUC) and
serum ferritin level has a negative correlation (r = -0.205, P = 0.019).
Ferritin, acylcarnitine, and phenylacetylglutamine are associated with liver
damage, including free radical formation, deregulation of hepatic mitochondrial
beta-oxidation, and hyperammonaemia. Our findings reveal potential biomarkers
predictive of busulfan exposure and suggest that liver function may affect
busulfan exposure.
PMID- 28490734
TI - Identification and activation of TLR4-mediated signalling pathways by alginate
derived guluronate oligosaccharide in RAW264.7 macrophages.
AB - Alginate, a natural acidic polysaccharide extracted from marine brown seaweeds,
is composed of different blocks of beta-(1, 4)-D-mannuronate (M) and its C-5
epimer alpha-(1, 4)-L-guluronate (G). Alginate-derived guluronate oligosaccharide
(GOS) readily activates macrophages. However, to understand its role in immune
responses, further studies are needed to characterize GOS transport and
signalling. Our results show that GOS is recognized by and upregulates Toll-like
receptor 4 (TLR4) on RAW264.7 macrophages, followed by its endocytosis via TLR4.
Increased expression of TLR4 and myeloid differentiation protein 2 (MD2) results
in Akt phosphorylation and subsequent activation of both nuclear factor-kappaB
(NF-kappaB) and mechanistic target of rapamycin (mTOR). Moreover, GOS stimulates
mitogen-activated protein kinases (MAPKs); notably, c-Jun N-terminal kinase (JNK)
phosphorylation depends on TLR4 initiation. All these events contribute to the
production of inflammatory mediators, either together or separately. Our findings
also reveal that GOS induces cytoskeleton remodelling in RAW264.7 cells and
promotes macrophage proliferation in mice ascites, both of which improve innate
immunity. Conclusively, our investigation demonstrates that GOS, which is
dependent on TLR4, is taken up by macrophages and stimulates TLR4/Akt/NF-kappaB,
TLR4/Akt/mTOR and MAPK signalling pathways and exerts impressive immuno
stimulatory activity.
PMID- 28490735
TI - Design, Synthesis and Biological Evaluation of novel Hedgehog Inhibitors for
treating Pancreatic Cancer.
AB - Hedgehog (Hh) pathway is involved in epithelial-mesenchymal transition (EMT) and
cancer stem cell (CSC) maintenance resulting in tumor progression. GDC-0449, an
inhibitor of Hh pathway component smoothened (Smo) has shown promise in the
treatment of various cancers including pancreatic cancer. However, the emergence
of resistance during GDC-0449 treatment with numerous side effects limits its
use. Therefore, here we report the design, synthesis and evaluation of novel GDC
0449 analogs using N-[3-(2-pyridinyl) phenyl] benzamide scaffold. Cell-based
screening followed by molecular simulation revealed 2-chloro-N 1-[4-chloro-3-(2
pyridinyl)phenyl]-N 4,N 4-bis(2-pyridinylmethyl)-1,4-benzenedicarboxamide (MDB5)
as most potent analog, binding with an extra interactions in seven-transmembrane
(7-TM) domain of Smo due to an additional 2-pyridylmethyl group than GDC-0449.
Moreover, MDB5 was more efficient in inhibiting Hh pathway components as measured
by Gli-1 and Shh at transcriptional and translational levels. Additionally, a
significant reduction of ALDH1, CD44 and Oct-3/4, key markers of pancreatic CSC
was observed when MIA PaCa-2 cells were treated with MDB5 compared to GDC-0449.
In a pancreatic tumor mouse model, MDB5 containing nanoparticles treated group
showed significant inhibition of tumor growth without loss in body weight. These
evidence highlight the enhanced Hh pathway inhibition and anticancer properties
of MDB5 leaving a platform for mono and/or combination therapy.
PMID- 28490736
TI - Extracellular Vesicles Carry HIV Env and Facilitate Hiv Infection of Human
Lymphoid Tissue.
AB - Cells productively infected with HIV-1 release virions along with extracellular
vesicles (EVs) whose biogenesis, size, and physical properties resemble those of
retroviruses. Here, we found that a significant number of EVs (exosomes) released
by HIV-1 infected cells carry gp120 (Env), a viral protein that mediates virus
attachment and fusion to target cells, and also facilitates HIV infection in
various indirect ways. Depletion of viral preparations of EVs, in particular of
those that carry gp120, decreases viral infection of human lymphoid tissue ex
vivo. Thus, EVs that carry Env identified in our work seem to facilitate HIV
infection and therefore may constitute a new therapeutic target for antiviral
strategy.
PMID- 28490737
TI - Intradermal administration of IL-33 induces allergic airway inflammation.
AB - Approximately half of all atopic dermatitis (AD) patients subsequently develop
asthma, particularly those with severe AD. This association, suggesting a role
for AD as an entry point for subsequent allergic disease, is a phenomenon known
as the "atopic march". While the underlying cause of the atopic march remains
unknown, recent evidence suggests that epithelial cell (EC)-derived cytokines
play a major role. We showed that mice exposed to antigen through the skin, in
the presence of IL-33, developed antigen-specific airway inflammation when later
challenged in the lung. IL-33 signaling was dispensable during effector/challenge
phase. These data reveal critical roles for IL-33 in the "atopic march" and will
offer a new therapeutic target in the treatment and prevention of allergic
asthma.
PMID- 28490738
TI - Model-guided control of hippocampal discharges by local direct current
stimulation.
AB - Neurostimulation is an emerging treatment for drug-resistant epilepsies when
surgery is contraindicated. Recent clinical results demonstrate significant
seizure frequency reduction in epileptic patients, however the mechanisms
underlying this therapeutic effect are largely unknown. This study aimed at
gaining insights into local direct current stimulation (LDCS) effects on
hyperexcitable tissue, by i) analyzing the impact of electrical currents locally
applied on epileptogenic brain regions, and ii) characterizing currents achieving
an "anti-epileptic" effect (excitability reduction). First, a neural mass model
of hippocampal circuits was extended to accurately reproduce the features of
hippocampal paroxysmal discharges (HPD) observed in a mouse model of epilepsy.
Second, model predictions regarding current intensity and stimulation polarity
were confronted to in vivo mice recordings during LDCS (n = 8). The neural mass
model was able to generate realistic hippocampal discharges. Simulation of LDCS
in the model pointed at a significant decrease of simulated HPD (in duration and
occurrence rate, not in amplitude) for cathodal stimulation, which was
successfully verified experimentally in epileptic mice. Despite the simplicity of
our stimulation protocol, these results contribute to a better understanding of
clinical benefits observed in epileptic patients with implanted neurostimulators.
Our results also provide further support for model-guided design of
neuromodulation therapy.
PMID- 28490739
TI - Honokiol inhibits ultraviolet radiation-induced immunosuppression through
inhibition of ultraviolet-induced inflammation and DNA hypermethylation in mouse
skin.
AB - Ultraviolet (UV) radiation exposure induces immunosuppression, which contributes
to the development of cutaneous malignancies. We investigated the effects of
honokiol, a phytochemical found in plants of the genus Magnolia, on UVB-induced
immunosuppression using contact hypersensitivity (CHS) as a model in C3H/HeN
mice. Topical application of honokiol (0.5 and 1.0 mg/cm2 skin area) had a
significant preventive effect on UVB-induced suppression of the CHS response. The
inflammatory mediators, COX-2 and PGE2, played a key role in this effect, as
indicated by honokiol inhibition of cyclooxygenase-2 (COX-2) expression and PGE2
production in the UVB-exposed skin. Honokiol application also inhibited UVB
induced DNA hypermethylation and its elevation of the levels of TET enzyme, which
is responsible for DNA demethylation in UVB-exposed skin. This was consistent
with the restoration of the CHS response in mice treated with the DNA
demethylating agent, 5-aza-2'-deoxycytidine, after UVB exposure. There was no
significant difference in the levels of inhibition of UVB-induced
immunosuppression amongst mice that were treated topically with available anti
cancer drugs (imiquimod and 5-fluorouracil). This study is the first to show that
honokiol has the ability to inhibit UVB-induced immunosuppression in preclinical
model and, thus, has potential for use as a chemopreventive strategy for UVB
radiation-induced malignancies.
PMID- 28490740
TI - Presence of heterocyclic amine carcinogens in home-cooked and fast-food camel
meat burgers commonly consumed in Saudi Arabia.
AB - Heterocyclic amines (HCAs) are formed by cooking protein-rich foods, for
instance, meat and fish, and are listed as possible human carcinogens. In the
present study, the presence of five potential HCAs (IQ, MeIQ, MeIQx, 4,8-DiMeIQx,
and PhIP) in cooked camel meat burgers was analyzed for the first time. The
analysis was performed in home-cooked and fast-food burger samples containing
food additives. The applied cooking technique for the home-cooked samples was pan
frying for a controlled cooking time and temperature. In the control cooked meat
samples (samples that contained no food additives), the concentrations of MeIQx,
4,8-DiMeIQx, and PhIP ranged from 2.47 ng/g to 4.89 ng/g, whereas IQ and MeIQ
were found to be below the limit of quantification. The concentrations contents
of MeIQx, 4,8-DiMeIQx, and PhIP in the home-cooked and fast-food samples ranged
from 1.52 ng/g to 2.13 ng/g and 1.85 ng/g to 3.46 ng/g, respectively. IQ and MeIQ
were not detected in either type of sample. In comparison to the control samples,
the home-cooked and fast-food samples produced lower levels of HCAs. Such
observations could result from the existence of antioxidants in incorporated food
additives, which induce pro-oxidative effects with the successive formation
and/or scavenging of free radicals.
PMID- 28490741
TI - Circulating miRNA-21-5p as a diagnostic biomarker for pancreatic cancer: evidence
from comprehensive miRNA expression profiling analysis and clinical validation.
AB - Pancreatic cancer (PC) is a highly fatal disease worldwide and is often
misdiagnosed in its early stages. The exploration of novel non-invasive
biomarkers will definitely benefit PC patients. Recently, circulating miRNAs in
body fluids are emerging as non-invasive biomarkers for PC diagnosis. In this
study, we first conducted comprehensive robust rank aggregation (RRA) analysis
based on 21 published miRome profiling studies. We statistically identified and
clinically validated a miRNA expression pattern in PC patients. These miRNAs
consisted of four up-regulated (hsa-miR-21-5p, hsa-miR-31-5p, hsa-miR-210-3p and
hsa-miR-155-5p) and three down-regulated miRNAs (hsa-miR-217, hsa-miR-148a-3p and
hsa-miR-375). Among them, hsa-miR-21-5p was one of the most highly expressed
miRNAs in the serum of PC patients. Our validation test further suggested a
relatively high accuracy of serum hsa-miR-21-5p levels in the diagnosis of PC,
with a sensitivity of 0.77 and a specificity of 0.80. Finally, a diagnostic meta
analysis based on 9 studies also revealed favorable sensitivity and specificity
of circulating hsa-miR-21-5p for the diagnosis of PC (pooled sensitivity and
specificity were 0.76 and 0.74, respectively), which was consistent with our
findings. Taken together, as one of the most aberrantly expressed miRNAs in PC,
circulating hsa-miR-21-5p might be a promising serum biomarker in patients with
PC.
PMID- 28490742
TI - Fabrication and Wettability Study of WO3 Coated Photocatalytic Membrane for Oil
Water Separation: A Comparative Study with ZnO Coated Membrane.
AB - Superhydrophilic and underwater superoleophobic surfaces were fabricated by
facile spray coating of nanostructured WO3 on stainless steel meshes and compared
its performance in oil-water separation with ZnO coated meshes. The gravity
driven oil-water separation system was designed using these surfaces as the
separation media and it was noticed that WO3 coated stainless steel mesh showed
high separation efficiency (99%), with pore size as high as 150 um, whereas ZnO
coated surfaces failed in the process of oil-water separation when the pore
exceeded 50 um size. Since, nanostructured WO3 is a well known catalyst, the
simultaneous photocatalytic degradation of organic pollutants present in the
separated water from the oil water separation process were tested using WO3
coated surfaces under UV radiation and the efficiency of this degradation was
found to be quite significant. These results assure that with little
improvisation on the oil water separation system, these surfaces can be made
multifunctional to work simultaneously for oil-water separation and
demineralization of organic pollutants from the separated water. Fabrication of
the separating surface, their morphological characteristics, wettability, oil
water separation efficiency and photo-catalytic degradation efficiency are
enunciated.
PMID- 28490743
TI - Allelic imbalance of somatic mutations in cancer genomes and transcriptomes.
AB - Somatic mutations in cancer genomes often show allelic imbalance (AI) of mutation
abundance between the genome and transcriptome, but there is not yet a systematic
understanding of AI. In this study, we performed large-scale DNA and RNA AI
analyses of >100,000 somatic mutations in >2,000 cancer specimens across five
tumor types using the exome and transcriptome sequencing data of the Cancer
Genome Atlas consortium. First, AI analysis of nonsense mutations and frameshift
indels revealed that nonsense-mediated decay is typical in cancer genomes, and we
identified the relationship between the extent of AI and the location of
mutations in addition to the well-recognized 50-nt rules. Second, the AI with
splice site mutations may reflect the extent of intron retention and is
frequently observed in known tumor suppressor genes. For missense mutations, we
observed that mutations frequently subject to AI are enriched to genes related to
cancer, especially those of apoptosis and the extracellular matrix, and C:G > A:T
transversions. Our results suggest that mutations in known cancer-related genes
and their transcripts are subjected to different levels of transcriptional or
posttranscriptional regulation compared to wildtype alleles and may add an
additional regulatory layer to the functions of cancer-relevant genes.
PMID- 28490744
TI - Precision Radiology: Predicting longevity using feature engineering and deep
learning methods in a radiomics framework.
AB - Precision medicine approaches rely on obtaining precise knowledge of the true
state of health of an individual patient, which results from a combination of
their genetic risks and environmental exposures. This approach is currently
limited by the lack of effective and efficient non-invasive medical tests to
define the full range of phenotypic variation associated with individual health.
Such knowledge is critical for improved early intervention, for better treatment
decisions, and for ameliorating the steadily worsening epidemic of chronic
disease. We present proof-of-concept experiments to demonstrate how routinely
acquired cross-sectional CT imaging may be used to predict patient longevity as a
proxy for overall individual health and disease status using computer image
analysis techniques. Despite the limitations of a modest dataset and the use of
off-the-shelf machine learning methods, our results are comparable to previous
'manual' clinical methods for longevity prediction. This work demonstrates that
radiomics techniques can be used to extract biomarkers relevant to one of the
most widely used outcomes in epidemiological and clinical research - mortality,
and that deep learning with convolutional neural networks can be usefully applied
to radiomics research. Computer image analysis applied to routinely collected
medical images offers substantial potential to enhance precision medicine
initiatives.
PMID- 28490745
TI - A nanofabricated, monolithic, path-separated electron interferometer.
AB - Progress in nanofabrication technology has enabled the development of numerous
electron optic elements for enhancing image contrast and manipulating electron
wave functions. Here, we describe a modular, self-aligned, amplitude-division
electron interferometer in a conventional transmission electron microscope. The
interferometer consists of two 45-nm-thick silicon layers separated by 20 MUm.
This interferometer is fabricated from a single-crystal silicon cantilever on a
transmission electron microscope grid by gallium focused-ion-beam milling. Using
this interferometer, we obtain interference fringes in a Mach-Zehnder geometry in
an unmodified 200 kV transmission electron microscope. The fringes have a period
of 0.32 nm, which corresponds to the [111] lattice planes of silicon, and a
maximum contrast of 15%. We use convergent-beam electron diffraction to quantify
grating alignment and coherence. This design can potentially be scaled to
millimeter-scale, and used in electron holography. It could also be applied to
perform fundamental physics experiments, such as interaction-free measurement
with electrons.
PMID- 28490746
TI - Pathogenic p62/SQSTM1 mutations impair energy metabolism through limitation of
mitochondrial substrates.
AB - Abnormal mitochondrial function has been found in patients with frontotemporal
dementia (FTD) and amyotrophic lateral sclerosis (ALS). Mutations in the p62 gene
(also known as SQSTM1) which encodes the p62 protein have been reported in both
disorders supporting the idea of an ALS/FTD continuum. In this work the role of
p62 in energy metabolism was studied in fibroblasts from FTD patients carrying
two independent pathogenic mutations in the p62 gene, and in a p62-knock-down
(p62 KD) human dopaminergic neuroblastoma cell line (SH-SY5Y). We found that p62
deficiency is associated with inhibited complex I mitochondrial respiration due
to lack of NADH for the electron transport chain. This deficiency was also
associated with increased levels of NADPH reflecting a higher activation of
pentose phosphate pathway as this is accompanied with higher cytosolic reduced
glutathione (GSH) levels. Complex I inhibition resulted in lower mitochondrial
membrane potential and higher cytosolic ROS production. Pharmacological
activation of transcription factor Nrf2 increased mitochondrial NADH levels and
restored mitochondrial membrane potential in p62-deficient cells. Our results
suggest that the phenotype is caused by a loss-of-function effect, because
similar alterations were found both in the mutant fibroblasts and the p62 KD
model. These findings highlight the implication of energy metabolism in
pathophysiological events associated with p62 deficiency.
PMID- 28490747
TI - Structural Basis for Importin-alpha Binding of the Human Immunodeficiency Virus
Tat.
AB - HIV-1 has caused 35 million deaths globally, and approximately the same number is
currently living with HIV-1. The trans-activator of transcription (Tat) protein
of HIV-1 plays an important regulatory function in the virus life cycle,
responsible for regulating the reverse transcription of the viral genome RNA. Tat
is found in the nucleus of infected cells, but can also invade uninfected
neighbouring cells. Regions within Tat responsible for these cellular
localisations are overlapping and include a nuclear localisation signal (NLS)
spanning 48GRKKRR, and a cell penetrating peptide (CPP) signal spanning
48GRKKRRQRRRAPQN. However, the mechanism by which this NLS/CPP region mediates
interaction with the nuclear import receptors remains to be resolved
structurally. Here, we establish that the HIV-1 Tat:NLS/CPP is able to form a
stable and direct interaction with the classical nuclear import receptor importin
alpha and using x-ray crystallography, we have determined the molecular interface
and binding determinants to a resolution of 2.0 A. We show for the first time
that the interface is the same as host factors such as Ku70 and Ku80, rather than
other virus proteins such as Ebola VP24 that bind on the outer surface of
importin-alpha.
PMID- 28490748
TI - Nuclear DNA markers for identification of Beluga and Sterlet sturgeons and their
interspecific Bester hybrid.
AB - Sturgeons (Acipenseriformes) are among the most endangered species in the world
due to fragmentation and destruction of their natural habitats and to
overexploitation, mainly for highly priced caviar. This has led to the
development of sturgeon culture, originally for reintroduction, but more recently
for caviar production. In both cases, accurate species identification is
essential. We report a new tool for accurate identification of Huso huso and
Acipenser ruthenus based on nuclear DNA markers. We employed ddRAD sequencing to
identify species-specific nucleotide variants, which served as specific binding
sites for diagnostic primers. The primers allowed identification of Huso huso and
Acipenser ruthenus as well as their discrimination from A. baerii, A. schrenckii,
A. gueldenstaedtii, A. stellatus, A. persicus, A. mikadoi, A. transmontanus, and
H. dauricus and identification of A. ruthenus and H. huso hybrids with these
species, except hybrid between A. ruthenus and A. stellatus. The species-specific
primers also allowed identification of bester (H. huso * A. ruthenus), the most
commercially exploited sturgeon hybrid. The tool, based on simple PCR and gel
electrophoresis, is rapid, inexpensive, and reproducible. It will contribute to
conservation of remaining wild populations of A. ruthenus and H. huso, as well as
to traceability of their products.
PMID- 28490749
TI - Characterization of Product and Potential Mechanism of Cr(VI) Reduction by
Anaerobic Activated Sludge in a Sequencing Batch Reactor.
AB - Bioremediation of Cr(VI) and nitrate is considered as a promising and cost
effective alternative to chemical and physical methods. However, organo-Cr(III)
complexes in effluent generally causes environmental concerns due to second
pollution. Here, Cr(VI) reduction and immobilization efficiencies of anaerobic
activated sludge were investigated. Anaerobic activated sludge showed strong
reduction ability of Cr(VI) and possessed a great potential of Cr(III)
immobilization. Almost 100.0 mg l-1 Cr(VI) could be completely reduced and
immobilized by anaerobic activated sludge in a sequencing batch reactor in 24 h.
And most generated Cr(III) was accumulated outside of sludge cells. Extracellular
polymeric substances (EPS) could bind to Cr(VI) and form EPS-Cr(VI) interaction
to reduce the toxic effect of Cr(VI) and promote the Cr(VI) reduction. Protein
like and humic-like substances were responsible for binding with Cr(VI),
meanwhile the process was a thermodynamically favorable binding reaction. Then
Cr(VI) was reduced to Cr(III) by membrane-associated chromate reductase of
sludge. Eventually, the generated Cr(III) might exist as poly-nuclear Cr(III)
complexes adhered to sludge surfaces.
PMID- 28490750
TI - DV21 decreases excitability of cortical pyramidal neurons and acts in epilepsy.
AB - Epilepsy is one of the most common neurological disorders and the administration
of antiepileptic drugs (AEDs) is the most common treatment. Although there are
more than 15 AEDs available, a third of epilepsy patients remain refractory to
available drugs, so novel effective drugs are needed. Here, we found that DV21,
which is a natural triterpenoid compound extracted from plants of the
Asclepiadaceae family, significantly decreased the incidence and stages of
seizures in three classical drug-induced acute seizure models in C57BL/6 mice.
Furthermore, we also found that the antiepileptic effect of DV21 might be partly
mediated through reducing the excitability of cortical pyramidal neurons by
increasing M current, which are low-threshold non-inactivating voltage-gated
potassium currents. Moreover, the application of XE991, an inhibitor of M
current, could block most the antiepileptic effect of DV21. Taken together, our
results indicated that DV21 might be a novel leading compound for the treatment
of epilepsy.
PMID- 28490751
TI - Unexpected Efficacy of a Novel Sodium Channel Modulator in Dravet Syndrome.
AB - Dravet syndrome, an epileptic encephalopathy affecting children, largely results
from heterozygous loss-of-function mutations in the brain voltage-gated sodium
channel gene SCN1A. Heterozygous Scn1a knockout (Scn1a +/-) mice recapitulate the
severe epilepsy phenotype of Dravet syndrome and are an accepted animal model.
Because clinical observations suggest conventional sodium channel blocking
antiepileptic drugs may worsen the disease, we predicted the phenotype of Scn1a
+/- mice would be exacerbated by GS967, a potent, unconventional sodium channel
blocker. Unexpectedly, GS967 significantly improved survival of Scn1a +/- mice
and suppressed spontaneous seizures. By contrast, lamotrigine exacerbated the
seizure phenotype. Electrophysiological recordings of acutely dissociated neurons
revealed that chronic GS967-treatment had no impact on evoked action potential
firing frequency of interneurons, but did suppress aberrant spontaneous firing of
pyramidal neurons and was associated with significantly lower sodium current
density. Lamotrigine had no effects on neuronal excitability of either neuron
subtype. Additionally, chronically GS967-treated Scn1a +/- mice exhibited
normalized pyramidal neuron sodium current density and reduced hippocampal NaV1.6
protein levels, whereas lamotrigine treatment had no effect on either pyramidal
neuron sodium current or hippocampal NaV1.6 levels. Our findings demonstrate
unexpected efficacy of a novel sodium channel blocker in Dravet syndrome and
suggest a potential mechanism involving a secondary change in NaV1.6.
PMID- 28490752
TI - Design, Fabrication and Characterization of Pressure-Responsive Films Based on
The Orientation Dependence of Plasmonic Properties of Ag@Au Nanoplates.
AB - A novel pressure-responsive polymer composite film was developed based on Ag@Au
composite nanoplates (NPLs) and polyvinylpyrrolidone (PVP) by using Au
nanoparticles as concentration reference. The orientation change of Ag@Au NPLs is
impelled by the deformation of polymer matrix under pressure, resulting in its
localized surface plasmon resonance (LSPR) intensity change of in-plane dipolar
peak. The intensity ratio between plasmon peak of Au nanoparticles and in-plane
dipolar peak of Ag@Au NPLs relies on the intensity and duration of pressure. By
adjusting the viscosity of the polymer, the orientation change of LSPR may
respond to a wide range of stresses. This pressure sensitive film can be utilized
to record the magnitude and distribution of pressure between two contacting
surfaces via optical information.
PMID- 28490753
TI - WBC count predicts the risk of new-onset peripheral arterial disease in a Chinese
community-based population.
AB - This longitudinal cohort study investigated whether peripheral WBC counts could
predict peripheral arterial disease (PAD) incidence after a 2.3-year follow-up in
a Chinese community-based population without PAD at baseline. A total of 3555
Chinese subjects without fever and PAD at baseline from an atherosclerosis cohort
were included in our analysis. The ankle brachial index (ABI) was measured, and
PAD was defined as an ABI <0.9. Multivariate regression models were used to
evaluate the association of WBC count and new-onset PAD. The mean (+/-s.d.)
baseline WBC count was 6.11+/-1.54 * 109 l-1, the mean (+/-s.d.) ABI was 1.11+/
0.08 at baseline and the incidence of PAD was 2.7% over 2.3 years. WBC counts
were significantly associated with PAD incidence (odds ratio (OR)=1.27, 95%
confidence interval (CI): 1.14-1.41, P<0.0001) with every 1 * 109 l-1 increase in
WBC count. This relationship remained significant (OR=1.21, 95% CI: 1.08-1.36,
P=0.0014) even after adjusting for other variables. The highest WBC quartile
group had increased risk when compared with the lowest quartile group (OR=2.14,
95% CI: 1.09-4.22, P=0.027) in a multivariate logistic model. Furthermore, we did
not find significant heterogeneity among the analyzed subgroups based on sex
(male or female), age (<60 or ?60 years old), body mass index (BMI, <25 or ?25 kg
m-2), current smoking, current drinking, hypertension, diabetes mellitus,
dyslipidemia or cardiovascular disease. In conclusion, elevated WBC counts
independently predict the risk of new-onset PAD in a Chinese community-based
population, supporting the hypothesis that systemic inflammation plays an
important role in PAD development.
PMID- 28490754
TI - Effect of alkaline microwaving pretreatment on anaerobic digestion and biogas
production of swine manure.
AB - Microwave assisted with alkaline (MW-A) condition was applied in the pretreatment
of swine manure, and the effect of the pretreatment on anaerobic treatment and
biogas production was evaluated in this study. The two main microwaving (MW)
parameters, microwaving power and reaction time, were optimized for the
pretreatment. Response surface methodology (RSM) was used to investigate the
effect of alkaline microwaving process for manure pretreatment at various values
of pH and energy input. Results showed that the manure disintegration degree was
maximized of 63.91% at energy input of 54 J/g and pH of 12.0, and variance
analysis indicated that pH value played a more important role in the pretreatment
than in energy input. Anaerobic digestion results demonstrated that MW-A
pretreatment not only significantly increased cumulative biogas production, but
also shortened the duration for a stable biogas production rate. Therefore, the
alkaline microwaving pretreatment could become an alternative process for
effective treatment of swine manure.
PMID- 28490755
TI - Thigmotaxis Mediates Trail Odour Disruption.
AB - Disruption of foraging using oversupply of ant trail pheromones is a novel pest
management application under investigation. It presents an opportunity to
investigate the interaction of sensory modalities by removal of one of the modes.
Superficially similar to sex pheromone-based mating disruption in moths, ant
trail pheromone disruption lacks an equivalent mechanistic understanding of how
the ants respond to an oversupply of their trail pheromone. Since significant
compromise of one sensory modality essential for trail following (chemotaxis) has
been demonstrated, we hypothesised that other sensory modalities such as
thigmotaxis could act to reduce the impact on olfactory disruption of foraging
behaviour. To test this, we provided a physical stimulus of thread to aid
trailing by Argentine ants otherwise under disruptive pheromone concentrations.
Trail following success was higher using a physical cue. While trail integrity
reduced under continuous over-supply of trail pheromone delivered directly on the
thread, provision of a physical cue in the form of thread slightly improved trail
following and mediated trail disruption from high concentrations upwind. Our
results indicate that ants are able to use physical structures to reduce but not
eliminate the effects of trail pheromone disruption.
PMID- 28490756
TI - Expressing acetylcholine receptors after innervation suppresses spontaneous
vesicle release and causes muscle fatigue.
AB - The formation and function of synapses are tightly orchestrated by the precise
timing of expression of specific molecules during development. In this study, we
determined how manipulating the timing of expression of postsynaptic
acetylcholine receptors (AChRs) impacts presynaptic release by establishing a
genetically engineered zebrafish line in which we can freely control the timing
of AChR expression in an AChR-less fish background. With the delayed induction of
AChR expression after an extensive period of AChR-less development, paralyzed
fish displayed a remarkable level of recovery, exhibiting a robust escape
response following developmental delay. Despite their apparent behavioral rescue,
synapse formation in these fish was significantly altered as a result of delayed
AChR expression. Motor neuron innervation determined the sites for AChR
clustering, a complete reversal of normal neuromuscular junction (NMJ)
development where AChR clustering precedes innervation. Most importantly, among
the three modes of presynaptic vesicle release, only the spontaneous release
machinery was strongly suppressed in these fish, while evoked vesicle release
remained relatively unaffected. Such a specific presynaptic change, which may
constitute a part of the compensatory mechanism in response to the absence of
postsynaptic AChRs, may underlie symptoms of neuromuscular diseases characterized
by reduced AChRs, such as myasthenia gravis.
PMID- 28490757
TI - Transcriptome and metabolite analysis identifies nitrogen utilization genes in
tea plant (Camellia sinensis).
AB - Applied nitrogen (N) fertilizer significantly increases the leaf yield. However,
most N is not utilized by the plant, negatively impacting the environment. To
date, little is known regarding N utilization genes and mechanisms in the leaf
production. To understand this, we investigated transcriptomes using RNA-seq and
amino acid levels with N treatment in tea (Camellia sinensis), the most popular
beverage crop. We identified 196 and 29 common differentially expressed genes in
roots and leaves, respectively, in response to ammonium in two tea varieties.
Among those genes, AMT, NRT and AQP for N uptake and GOGAT and GS for N
assimilation were the key genes, validated by RT-qPCR, which expressed in a
network manner with tissue specificity. Importantly, only AQP and three novel
DEGs associated with stress, manganese binding, and gibberellin-regulated
transcription factor were common in N responses across all tissues and varieties.
A hypothesized gene regulatory network for N was proposed. A strong statistical
correlation between key genes' expression and amino acid content was revealed.
The key genes and regulatory network improve our understanding of the molecular
mechanism of N usage and offer gene targets for plant improvement.
PMID- 28490758
TI - Identifying conformational changes with site-directed spin labeling reveals that
the GTPase domain of HydF is a molecular switch.
AB - [FeFe]-hydrogenases catalyse the reduction of protons to hydrogen at a complex
2Fe[4Fe4S] center called H-cluster. The assembly of this active site is a
multistep process involving three proteins, HydE, HydF and HydG. According to the
current models, HydF has the key double role of scaffold, upon which the final H
cluster precursor is assembled, and carrier to transfer it to the target
hydrogenase. The X-ray structure of HydF indicates that the protein is a
homodimer with both monomers carrying two functional domains: a C-terminal FeS
cluster-binding domain, where the precursor is assembled, and a N-terminal GTPase
domain, whose exact contribution to cluster biogenesis and hydrogenase activation
is still elusive. We previously obtained several hints suggesting that the
binding of GTP to HydF could be involved in the interactions of this scaffold
protein with the other maturases and with the hydrogenase itself. In this work,
by means of site directed spin labeling coupled to EPR/PELDOR spectroscopy, we
explored the conformational changes induced in a recombinant HydF protein by GTP
binding, and provide the first clue that the HydF GTPase domain could be involved
in the H-cluster assembly working as a molecular switch similarly to other known
small GTPases.
PMID- 28490759
TI - Comorbidity burden of patients with Parkinson's disease and Parkinsonism between
2003 and 2012: A multicentre, nationwide, retrospective study in China.
AB - Parkinson's disease (PD) and Parkinsonism are common neurodegenerative disorders
with continuously increasing prevalence, causing high global burdens. However,
data concerning the comorbidity burden of patients with PD or Parkinsonism in
China are lacking. To investigate the health condition and comorbidity burden, a
total of 3367 PD and 823 Parkinsonism patients were included from seven tertiary
hospitals in seven cities across China from 2003 to 2012. Their comorbidity
burden was collected and quantified by the Elixhauser Comorbidity Index (ECI) and
Charlson Comorbidity Index (CCI). The comorbidity spectra differed between PD and
Parkinsonism patients. Compared with PD patients, Parkinsonism patients were
older (69.8 +/- 11.5 vs. 67.9 +/- 11.4, P < 0.001); had a higher comorbidity
burden, including ECI (1.1 +/- 1.2 vs. 1.0 +/- 1.2, P < 0.001) and CCI (1.3 +/-
1.6 vs. 1.1 +/- 1.5, P < 0.001); and had higher hospitalization expenses. The ECI
(1.1 +/- 1.3 vs. 0.9 +/- 1.1, P < 0.001) and CCI (1.3 +/- 1.6 vs. 0.9 +/- 1.2, P
< 0.001) were higher in males than in females. The average length of stay and
daily hospitalization expenses increased with age, as did ECI and CCI. This is
the first study to report the disease burden of Chinese PD and Parkinsonism
patients. It provides useful information to better understand their health
status, and to raise the awareness of clinicians for providing better health
care.
PMID- 28490760
TI - Hormonal pleiotropy helps maintain queen signal honesty in a highly eusocial
wasp.
AB - In insect societies, both queens and workers produce chemicals that reliably
signal caste membership and reproductive status. The mechanisms that help to
maintain the honesty of such queen and fertility signals, however, remain poorly
studied. Here we test if queen signal honesty could be based on the shared
endocrine control of queen fertility and the production of specific signals. In
support of this "hormonal pleiotropy" hypothesis, we find that in the common
wasp, application of methoprene (a juveline hormone analogue) caused workers to
acquire a queen-like cuticular hydrocarbon profile, resulting in the
overproduction of known queen pheromones as well as some compounds typically
linked to worker fertility. By contrast, administration of precocene-I (a JH
inhibitor) had a tendency to have the opposite effect. Furthermore, a clear
gonadotropic effect of JH in queens was suggested by the fact that circulating
levels of JH were ca. 2 orders of magnitude higher in queens than those in
workers and virgin, non-egg-laying queens, even if methoprene or precocene
treatment did not affect the ovary development of workers. Overall, these results
suggest that queen signal honesty in this system is maintained by queen fertility
and queen signal production being under shared endocrine control.
PMID- 28490761
TI - Nanoscale Brownian heating by interacting magnetic dipolar particles.
AB - Clusters of magnetic nanoparticles have received considerable interest in various
research fields. Their capacity to generate heat under an alternating magnetic
field has recently opened the way to applications such as cancer therapy by
hyperthermia. This work is an attempt to investigate the collective effects of
interacting dipoles embedded in magnetic nano-particles (MNP) to predict their
thermal dissipation with a liquid. We first present a general approach, based on
the tracking of the microscopic dipole fluctuations, to access to the dissipation
spectra of any spatial distribution of MNPs. Without any other assumption that
the linear response regime, it is shown that increasing the particle
concentration (dipolar interactions) dramatically diminishes and blueshifts the
dissipation processes. This effect originates in a predominance of the coupling
energy over the Brownian torques, which create a long-range ordering that
saturates the response of the system to an external field. Consequently, the
particle density is of fundamental importance to the control of the absorption of
electromagnetic energy and its subsequent dissipation in the form of heat.
PMID- 28490762
TI - Nexus fermions in topological symmorphic crystalline metals.
AB - Topological metals and semimetals (TMs) have recently drawn significant interest.
These materials give rise to condensed matter realizations of many important
concepts in high-energy physics, leading to wide-ranging protected properties in
transport and spectroscopic experiments. It has been well-established that the
known TMs can be classified by the dimensionality of the topologically protected
band degeneracies. While Weyl and Dirac semimetals feature zero-dimensional
points, the band crossing of nodal-line semimetals forms a one-dimensional closed
loop. In this paper, we identify a TM that goes beyond the above paradigms. It
shows an exotic configuration of degeneracies without a well-defined
dimensionality. Specifically, it consists of 0D nexus with triple-degeneracy that
interconnects 1D lines with double-degeneracy. We show that, because of the novel
form of band crossing, the new TM cannot be described by the established results
that characterize the topology of the Dirac and Weyl nodes. Moreover, triply
degenerate nodes realize emergent fermionic quasiparticles not present in
relativistic quantum field theory. We present materials candidates. Our results
open the door for realizing new topological phenomena and fermions including
transport anomalies and spectroscopic responses in metallic crystals with
nontrivial topology beyond the Weyl/Dirac paradigm.
PMID- 28490763
TI - Methylglyoxal-induced glycation changes adipose tissue vascular architecture,
flow and expansion, leading to insulin resistance.
AB - Microvascular dysfunction has been suggested to trigger adipose tissue
dysfunction in obesity. This study investigates the hypothesis that glycation
impairs microvascular architecture and expandability with an impact on insulin
signalling. Animal models supplemented with methylglyoxal (MG), maintained with a
high-fat diet (HFD) or both (HFDMG) were studied for periepididymal adipose
(pEAT) tissue hypoxia and local and systemic insulin resistance. Dynamic contrast
enhanced magnetic resonance imaging (DCE-MRI) was used to quantify blood flow in
vivo, showing MG-induced reduction of pEAT blood flow. Increased adipocyte size
and leptin secretion were observed only in rats feeding the high-fat diet,
without the development of hypoxia. In turn, hypoxia was only observed when MG
was combined (HFDMG group), being associated with impaired activation of the
insulin receptor (Tyr1163), glucose intolerance and systemic and muscle insulin
resistance. Accordingly, the adipose tissue angiogenic assay has shown decreased
capillarization after dose-dependent MG exposure and glyoxalase-1 inhibition.
Thus, glycation impairs adipose tissue capillarization and blood flow, hampering
its expandability during a high-fat diet challenge and leading to hypoxia and
insulin resistance. Such events have systemic repercussions in glucose metabolism
and may lead to the onset of unhealthy obesity and progression to type 2
diabetes.
PMID- 28490764
TI - Progranulin deficiency causes the retinal ganglion cell loss during development.
AB - Astrocytes are glial cells that support and protect neurons in the central
nervous systems including the retina. Retinal ganglion cells (RGCs) are in
contact with the astrocytes and our earlier findings showed the reduction of the
number of cells in the ganglion cell layer in adult progranulin deficient mice.
In the present study, we focused on the time of activation of the astrocytes and
the alterations in the number of RGCs in the retina and optic nerve in
progranulin deficient mice. Our findings showed that the number of Brn3a-positive
cells was reduced and the expression of glial fibrillary acidic protein (GFAP)
was increased in progranulin deficient mice. The progranulin deficient mice had a
high expression of GFAP on postnatal day 9 (P9) but not on postnatal day 1. These
mice also had a decrease in the number of the Brn3a-positive cells on P9. Taken
together, these findings indicate that the absence of progranulin can affect the
survival of RGCs subsequent the activation of astrocytes during retinal
development.
PMID- 28490765
TI - Effect of genomics-related literacy on non-communicable diseases.
AB - Recent progress in genomic research has raised expectations for the development
of personalized preventive medicine, although genomics-related literacy of
patients will be essential. Thus, enhancing genomics-related literacy is crucial,
particularly for individuals with low genomics-related literacy because they
might otherwise miss the opportunity to receive personalized preventive care.
This should be especially emphasized when a lack of genomics-related literacy is
associated with elevated disease risk, because patients could therefore be
deprived of the added benefits of preventive interventions; however, whether such
an association exists is unclear. Association between genomics-related literacy,
calculated as the genomics literacy score (GLS), and the prevalence of non
communicable diseases was assessed using propensity score matching on 4646
participants (males: 1891; 40.7%). Notably, the low-GLS group (score below
median) presented a higher risk of hypertension (relative risk (RR) 1.09, 95%
confidence interval (CI) 1.03-1.16) and obesity (RR 1.11, 95% CI 1.01-1.22) than
the high-GLS group. Our results suggest that a low level of genomics-related
literacy could represent a risk factor for hypertension and obesity. Evaluating
genomics-related literacy could be used to identify a more appropriate population
for health and educational interventions.
PMID- 28490766
TI - SCA42 mutation analysis in a case series of Japanese patients with
spinocerebellar ataxia.
AB - Spinocerebellar ataxia (SCA) is a group of dominantly inherited heterogeneous
disorders in which 43 subtypes have been identified to date. Recently, Japanese
and French families with SCA type 42 (SCA42) were found to have a missense
mutation (c.5144G>A; R1715H) in CACNA1G. We performed genetic analysis of 84
unrelated families to find the prevalence of SCA42 in Japan. Two families were
found to have the previously reported missense mutation. Clinical presentations
of the affected members of these families were similar to those of the previously
reported French and Japanese families. Our study demonstrates that SCA42 exists
in small numbers in Japan, and further supports the idea that SCA42 is a slowly
progressive, pure cerebellar ataxia.
PMID- 28490767
TI - Biliverdin Reductase inhibitors did not improve severe unconjugated
hyperbilirubinemia in vivo.
AB - We aimed to identify potent biliverdin reductase (BVRA) inhibitors as a novel
concept for the treatment of severe unconjugated hyperbilirubinemia. 1280 FDA
approved compounds were screened in vitro for their ability to inhibit human and
rat BVRA activity and 2 6 compounds were identified as BVRA inhibitors .
Montelukast and Disulfiram were sel ected as potentially clinically applicable
drug s and tested to reduce serum unconjugated bilirubin (UCB) levels in the
Ugt1a1-deficient rat, a model for chronic unconjugated hyperbilirubinemia. Oral
administration of Disulfiram was toxic in the Ugt1a1-deficient rat (weight loss,
transaminase elevation). Oral Montelukast administration led to low serum
concentrations and did not alter serum UCB levels. Intraperitoneal injections of
Mont elukast resulted in concentrations up to 110 MUmol/L in serum and 400
MUmol/L in the liver. Still, serum UCB levels remained unaltered. This first
study on biliverdin reductase inhibition as a novel concept for treatment of
unconjugated hyperbilirubinemia identified putative in vitro BVRA inhibitors.
Montelukast, the clinically most suitable inhibitor, did not result in reduction
of serum UCB in the Ugt1a1-deficient rat. The proposed treatment strategy will
not result in amelioration of severe unconjugated hyperbilirubinemia in humans
without the identification or development of more potent BVRA inhibitors.
PMID- 28490768
TI - Analytical evidence of enamel hypomineralisation on permanent and primary molars
amongst past populations.
AB - Molar Incisor Hypomineralisation (MIH) and Hypomineralised Second Primary Molars
(HSPM) involve prevalent qualitative structural developmental anomalies of tooth
enamel affecting the first permanent molars (and often incisors) and the second
primary molars, respectively. These demarcated hypomineralised lesions of enamel
manifest as white-cream or yellow-brown opacities, with possible post-eruptive
localised loss of enamel. Aetiological hypotheses have involved contemporary life
factors (i.e. environmental pollutant exposure or early childhood medications) in
contrast to factors not limited to a specific time period (i.e. hypoxia at birth
or genetic predisposition). Evidence of MIH in ancient populations would
reinforce aetiological factors present for many centuries. By means of
microtomographic and X-ray fluorescence analyses the present study provides
evidence that (i) two archaeological specimens: "S407" (Sains-en-Gohelle, France,
12th-16th centuries) and "B335" (Beauvais, France, 15th-18th centuries) were MIH
affected, and (ii) one individual "S323" was affected by HSPM and MIH (Sains-en
Gohelle, France, 7th-11th centuries).
PMID- 28490769
TI - Increased cerebral expressions of MMPs, CLDN5, OCLN, ZO1 and AQPs are associated
with brain edema following fatal heat stroke.
AB - Human brain samples were collected from 46 autopsy cases, including 23 fatal heat
stroke cases and 23 age-matched controls. Nine candidate reference genes (PES1,
POLR2A, IPO8, HMBS, SDHA, GAPDH, UBC, B2M, ACTB) were evaluated in the cerebral
cortex of 10 forensic autopsy cases (5 heat stroke and 5 controls), using the
geNorm module in qBaseplus software. SDHA, POLR2A, IPO8 and HMBS were identified
as the most stable reference genes. Using these validated reference genes, mRNA
expressions of Matrix metalloproteinases (MMPs, MMP2 and MMP9), Claudin5 (CLDN5),
Occludin (OCLN), Zona occludens protein-1 (ZO1) and Aquaporins (AQPs, AQP1 and
AQP4) in the cerebral cortex were examined. Relative mRNA quantification using
Taqman real-time PCR assay demonstrated increased calibrated normalized relative
quantity (CNRQ) values of MMP9, CLDN5, OCLN, ZO1 and AQP4 in heat stroke cases.
Heat stroke cases showed an increase in brain water content, which was found to
be positively correlated with MMP9, OCLN, ZO1 and CLDN5 mRNA. When using one
conventional reference gene (GAPDH or ACTB) for normalization, no difference was
detected between heat stroke and controls. In immunostaining, only AQP4 showed
more intense staining in most heat stroke cases. The present study, for the first
time, reports increased cerebral MMP9, CLDN5, OCLN, ZO1 and AQP4 in heat stroke
and suggest a crucial role of reference gene selection when using postmortem
human tissues.
PMID- 28490770
TI - Misoprostol for medical treatment of missed abortion: a systematic review and
network meta-analysis.
AB - The efficacy and safety of misoprostol alone for missed abortion varied with
different regimens. To evaluate existing evidence for the medical management of
missed abortion using misoprostol, we undertook a comprehensive review and meta
analysis. The electronic literature search was conducted using PubMed, the
Cochrane Library, Embase, EBSCOhost Online Research Databases, Springer Link,
ScienceDirect, Web of Science, Ovid Medline and Google Scholar. 18 studies of
1802 participants were included in our analysis. Compared with vaginal
misoprostol of 800 ug or sublingual misoprostol of 600 ug, lower-dose regimens
(200 ug or 400 ug) by any route of administration tend to be significantly less
effective in producing abortion within about 24 hours. In terms of efficacy, the
most effective treatment was sublingual misoprostol of 600 ug and the least
effective was oral misoprostol of 400 ug. In terms of tolerability, vaginal
misoprostol of 400 ug was reported with fewer side effects and sublingual
misoprostol of 600 ug was reported with more side effects. Misoprostol is a non
invasive, effective medical method for completion of abortion in missed abortion.
Sublingual misoprostol of 600 ug or vaginal misoprostol of 800 ug may be a good
choice for the first dose. The ideal dose and medication interval of misoprostol
however needs to be further researched.
PMID- 28490771
TI - Some dietary factors can modulate the effect of the zinc transporters 8
polymorphism on the risk of metabolic syndrome.
AB - There are conflicting data on the impact of zinc transporter 8 (ZNT8) gene
variations on the metabolic syndrome (MetS). Hence, the effects of the
interaction between rs13266634 and dietary factors on the risk of MetS were
investigated in this study. Subjects of this nested case-control study were
selected from the participants in Tehran Lipid and Glucose Study. Each of the
cases (n = 817) was individually matched with a control. Dietary patterns were
determined using factor analysis. The ZNT8 rs13266634 were genotyped by the Tetra
refractory mutation system-polymerase chain reaction analysis. Two dietary
patterns were extracted. There were no significant interactions between the ZNT8
SNP and the dietary patterns on the risk of MetS or its components. An
interaction was observed between rs13266634 and the omega-3 fatty acid intakes on
the risk of MetS in subjects with the CC genotype (P interaction < 0.01). Zinc
modified the association of the ZNT8 variant with high fasting blood sugar (P
interaction = 0.05) in CC genotype carriers. An interaction was also observed
between rs13266634 and salty snacks at the risk of abdominal obesity (P
interaction < 0.05). Our findings suggest an interaction between omega-3 fatty
acids, zinc, salty snacks and rs13266634, which may affect the risk of MetS or
its components.
PMID- 28490772
TI - Flexible and compact hybrid metasurfaces for enhanced ultra high field in vivo
magnetic resonance imaging.
AB - Developments in metamaterials and related structures such as metasurfaces have
opened up new possibilities in designing materials and devices with unique
properties. Here we report a new hybrid metasurface structure, comprising a two
dimensional metamaterial surface and a very high permittivity dielectric
substrate, that has been designed to enhance the local performance of an ultra
high field MRI scanner. This new flexible and compact resonant structure is the
first metasurface which can be integrated with multi-element close-fitting
receive coil arrays that are used for all clinical MRI scans. We demonstrate the
utility of the metasurface acquiring in-vivo human brain images and proton MR
spectra with enhanced local sensitivity on a commercial 7 Tesla system.
PMID- 28490773
TI - Rapid face adaptation distributes representation in inferior-temporal cortex
across time and neuronal dimensions.
AB - Neuronal networks of the brain adapt their information processing according to
the history of stimuli. Whereas most studies have linked adaptation to repetition
suppression, recurrent connections within a network and disinhibition due to
adaptation predict more complex response patterns. The main questions of this
study are as follows: what is the effect of the selectivity of neurons on
suppression/enhancement of neural responses? What are the consequences of
adaptation on information representation in neural population and the temporal
structure of response patterns? We studied rapid face adaptation using spiking
activities of neurons in the inferior-temporal (IT) cortex. Investigating the
responses of neurons, within a wide range from negative to positive face
selectivity, showed that despite the peak amplitude suppression in highly
positive selective neurons, responses were enhanced in most other neurons. This
enhancement can be attributed to disinhibition due to adaptation. Delayed and
distributed responses were observed for positive selective neurons. Principal
component analysis of the IT population responses over time revealed that
repetition of face stimuli resulted in temporal decorrelation of the network
activity. The contributions of the main and higher neuronal dimensions were
changed under an adaptation condition, where more neuronal dimensions were used
to encode repeated face stimuli.
PMID- 28490774
TI - DMBA acts on cumulus cells to desynchronize nuclear and cytoplasmic maturation of
pig oocytes.
AB - As an environmental pollutant and carcinogen, 7,12-dimethylbenz[a]anthracene
(DMBA) can destroy ovarian follicles at all developmental stages in rodents.
However, the underlying molecular mechanism remains obscure. In the present
study, we aim to address how DMBA affects the in vitro maturation and development
of porcine oocytes. We discovered that for 20 MUM DMBA-treated cumulus-oocyte
complexes (COCs), the rate of oocyte germinal vesicle breakdown (GVBD) was
significantly altered, and the extrusion rate of first polar body was increased.
Moreover, oocytes from 20 MUM DMBA-treated COCs had significant down-regulation
of H3K9me3 and H3K27me3, up-regulation of H3K36me3, higher incidence of DNA
double strand breaks (DSBs) and early apoptosis. In striking contrast, none of
these changes happened to 20 MUM DMBA-treated cumulus-denuded oocytes (CDOs).
Furthermore, 20 MUM DMBA treatment increased the reactive oxygen species (ROS)
level, decreased mitochondrial membrane potential (Delta Psim), and inhibited
developmental competence for oocytes from both COC and CDO groups. Collectively,
our data indicate DMBA could act on cumulus cells via the gap junction to disturb
the synchronization of nuclear and ooplasmic maturation, and reduce the
developmental competence of oocytes.
PMID- 28490775
TI - Metasurface Freeform Nanophotonics.
AB - Freeform optics aims to expand the toolkit of optical elements by allowing for
more complex phase geometries beyond rotational symmetry. Complex, asymmetric
curvatures are employed to enhance the performance of optical components while
minimizing their size. Unfortunately, these high curvatures and complex forms are
often difficult to manufacture with current technologies, especially at the
micron scale. Metasurfaces are planar sub-wavelength structures that can control
the phase, amplitude, and polarization of incident light, and can thereby mimic
complex geometric curvatures on a flat, wavelength-scale thick surface. We
present a methodology for designing analogues of freeform optics using a silicon
nitride based metasurface platform for operation at visible wavelengths. We
demonstrate a cubic phase plate with a point spread function exhibiting enhanced
depth of field over 300 micron along the optical axis with potential for
performing metasurface-based white light imaging, and an Alvarez lens with a
tunable focal length range of over 2.5 mm corresponding to a change in optical
power of ~1600 diopters with 100 micron of total mechanical displacement. The
adaptation of freeform optics to a sub-wavelength metasurface platform allows for
further miniaturization of optical components and offers a scalable route toward
implementing near-arbitrary geometric curvatures in nanophotonics.
PMID- 28490776
TI - Learning and memory: Consolidation circuitry.
PMID- 28490777
TI - Working memory: Keeping short-term memories alive.
PMID- 28490778
TI - Brain ageing: A youthful reminder.
PMID- 28490779
TI - Large scale phosphoprotein profiling to explore Drosophila cold acclimation
regulatory mechanisms.
AB - The regulatory mechanisms involved in the acquisition of thermal tolerance are
unknown in insects. Reversible phosphorylation is a widespread post-translational
modification that can rapidly alter proteins function(s). Here, we conducted a
large-scale comparative screening of phosphorylation networks in adult Drosophila
flies that were cold-acclimated versus control. Using a modified SIMAC method
followed by a multiple MS analysis strategy, we identified a large collection of
phosphopeptides (about 1600) and phosphoproteins (about 500) in both groups, with
good enrichment efficacy (80%). The saturation curves from the four biological
replicates revealed that the phosphoproteome was rather well covered under our
experimental conditions. Acclimation evoked a strong phosphoproteomic signal
characterized by large sets of unique and differential phosphoproteins. These
were involved in several major GO superclusters of which cytoskeleton
organization, positive regulation of transport, cell cycle, and RNA processing
were particularly enriched. Data suggest that phosphoproteomic changes in
response to acclimation were mainly localized within cytoskeletal network, and
particularly within microtubule associated complexes. This study opens up novel
research avenues for exploring the complex regulatory networks that lead to
acquired thermal tolerance.
PMID- 28490780
TI - Intrabasin Variability of East Pacific Tropical Cyclones During ENSO Regulated by
Central American Gap Winds.
AB - Hurricane Patricia in 2015 was the strongest Pacific hurricane to make landfall
in Mexico. Although Patricia fortuitously spared major cities, it reminded us of
the threat tropical cyclones (TCs) pose in the eastern North Pacific (ENP) and
the importance of improving our understanding and prediction of ENP TCs.
Patricia's intensity and the active 2015 ENP hurricane season have been partially
attributed to the strong El Nino in 2015, however there is still a lack of
fundamental understanding of the relationship between El Nino-Southern
Oscillation (ENSO) and ENP TCs. Here, we demonstrate that ENSO drives intrabasin
variability of ENP TCs, with enhanced (reduced) TC frequency in the western
portion of the ENP during El Nino (La Nina), but reduced (enhanced) TC frequency
in the eastern nearshore area, where landfalling TCs preferentially form. This
intrabasin difference is primarily driven by the Central American Gap Winds
(CAGW), which intensify (weaken) during El Nino (La Nina), producing low-level
anticyclonic (cyclonic) relative vorticity anomalies and thus an unfavorable
(favorable) environment for TC genesis. These findings shed new light on the
dynamics linking ENP TC activity to ENSO, and highlight the importance of
improving CAGW representation in models to make skillful seasonal forecasts of
ENP TCs.
PMID- 28490781
TI - Identification of Long Noncoding RNAs Deregulated in Papillary Thyroid Cancer and
Correlated with BRAFV600E Mutation by Bioinformatics Integrative Analysis.
AB - Papillary Thyroid Cancer (PTC) is an endocrine malignancy in which BRAFV600E
oncogenic mutation induces the most aggressive phenotype. In this way,
considering that lncRNAs are arising as key players in oncogenesis, it is of high
interest the identification of BRAFV600E-associated long noncoding RNAs, which
can provide possible candidates for secondary mechanisms of BRAF-induced
malignancy in PTC. In this study, we identified differentially expressed lncRNAs
correlated with BRAFV600E in PTC and, also, extended the cohort of paired normal
and PTC samples to more accurately identify differentially expressed lncRNAs
between these conditions. Indirectly validated targets of the differentially
expressed lncRNAs in PTC compared to matched normal samples demonstrated an
involvement in surface receptors responsible for signal transduction and cell
adhesion, as well as, regulation of cell death, proliferation and apoptosis.
Targets of BRAFV600E-correlated lncRNAs are mainly involved in calcium signaling
pathway, ECM-receptor interaction and MAPK pathway. In summary, our study
provides candidate lncRNAs that can be either used for future studies related to
diagnosis/prognosis or as targets for PTC management.
PMID- 28490782
TI - Mangrove dieback during fluctuating sea levels.
AB - Recent evidence indicates that climate change and intensification of the El Nino
Southern Oscillation (ENSO) has increased variation in sea level. Although
widespread impacts on intertidal ecosystems are anticipated to arise from the sea
level seesaw associated with climate change, none have yet been demonstrated.
Intertidal ecosystems, including mangrove forests are among those ecosystems that
are highly vulnerable to sea level rise, but they may also be vulnerable to sea
level variability and extreme low sea level events. During 16 years of monitoring
of a mangrove forest in Mangrove Bay in north Western Australia, we documented
two forest dieback events, the most recent one being coincident with the large
scale dieback of mangroves in the Gulf of Carpentaria in northern Australia.
Diebacks in Mangrove Bay were coincident with periods of very low sea level,
which were associated with increased soil salinization of 20-30% above pre-event
levels, leading to canopy loss, reduced Normalized Difference Vegetation Index
(NDVI) and reduced recruitment. Our study indicates that an intensification of
ENSO will have negative effects on some mangrove forests in parts of the Indo
Pacific that will exacerbate other pressures.
PMID- 28490784
TI - Osteoarthritis: Removing old chondrocytes to combat disease.
PMID- 28490783
TI - Multiple biomarker responses (serum biochemistry, oxidative stress, genotoxicity
and histopathology) in Channa punctatus exposed to heavy metal loaded waste
water.
AB - Experiments were conducted to investigate the health of fish Channa punctatus
inhabiting heavy metal-loaded waste water. Heavy metals in the order of Fe > Mn >
Zn > Co > Ni > Cu = Cr were present in the waste water. Gills had high metal load
followed by liver and then kidney. Albumin, albumin to globulin (A:G) ratio,
triglyceride, high density lipoprotein (HDL) and very low density lipoprotein
(VLDL) were found to be lower but phospholipid, low density lipoprotein (LDL),
total protein, lipid and cholesterol were higher as compared to the reference.
Oxidative stress markers such as superoxide dismutase (SOD), catalase (CAT),
glutathione S transferase (GST) and lipid peroxidation (LPO) were significantly
higher in all tissues, whereas reduced glutathione (GSH) levels were
comparatively low. Damage to DNA was observed with significantly higher mean tail
length of comets in the exposed fish gill cells (30.9 um) followed by liver (24.3
um) and kidney (20.6 um) as compared to reference fish (5.2, 4.8 and 5.9 um
respectively). Histopathology in gill, liver and kidney also showed marked
damage. Integrated biochemical, oxidative stress, genotoxicity and
histopathological findings are valuable biomarkers for native fish adaptive
patterns, and monitoring of water quality/pollution of freshwater ecosystems.
PMID- 28490786
TI - Rheumatoid arthritis: Don't swallow the NETs.
PMID- 28490785
TI - The rise of IL-2 therapy - a picture beyond Treg cells.
PMID- 28490787
TI - The changing face of polyarteritis nodosa and necrotizing vasculitis.
AB - Polyarteritis nodosa (PAN) is a vasculitic disease characterized primarily by
necrotizing vasculitis - inflammatory lesions in blood vessels that lead to
vessel wall necrosis. Our understanding of PAN and necrotizing vasculitis has
evolved over time. In addition to PAN, necrotizing vasculitis is now a recognized
feature of a broad range of diseases with different aetiopathogenesis. For
example, necrotizing vasculitis associated with hepatitis B virus infection has a
different aetiopathogeneis to PAN and is now classified as a separate disease.
Additionally, although 'classic' PAN is not an inherited disease, mutations in
specific genes, such as ADA2 (also known as CECR1), can result in a necrotizing
vasculopathy similar to PAN. The literature also suggests that the course of PAN
differs in childhood-onset disease and in cases confined to the skin (so-called
cutaneous PAN). Dissecting PAN and other autoinflammatory diseases with PAN-like
features has enabled more-specific therapies and might also help us better
understand the pathogenesis of these devastating conditions.
PMID- 28490788
TI - Low-dose IL-2 therapy - a complex scenario that remains to be further explored.
PMID- 28490789
TI - Epidemiology: Time to revisit the concept of reactive arthritis.
PMID- 28490790
TI - Entropy of radiation: the unseen side of light.
AB - Despite the fact that 2015 was the international year of light, no mention was
made of the fact that radiation contains entropy as well as energy, with
different spectral distributions. Whereas the energy function has been vastly
studied, the radiation entropy distribution has not been analysed at the same
speed. The Mode of the energy distribution is well known -Wien's law- and
Planck's law has been analytically integrated recently, but no similar advances
have been made for the entropy. This paper focuses on the characterization of the
entropy of radiation distribution from an statistical perspective, obtaining a
Wien's like law for the Mode and integrating the entropy for the Median and the
Mean in polylogarithms, and calculating the Variance, Skewness and Kurtosis of
the function. Once these features are known, the increasing importance of
radiation entropy analysis is evidenced in three different interdisciplinary
applications: defining and determining the second law Photosynthetically Active
Radiation (PAR) region efficiency, measuring the entropy production in the
Earth's atmosphere, and showing how human vision evolution was driven by the
entropy content in radiation.
PMID- 28490791
TI - Intact word processing in developmental prosopagnosia.
AB - A wealth of evidence from behavioural, neuropsychological and neuroimaging
research supports the view that face recognition is reliant upon a domain
specific network that does not process words. In contrast, the recent many-to
many model of visual recognition posits that brain areas involved in word and
face recognition are functionally integrated. Developmental prosopagnosia (DP) is
characterised by severe deficits in the recognition of faces, which the many-to
many model predicts should negatively affect word recognition. Alternatively,
domain-specific accounts suggest that impairments in face and word processing
need not go hand in hand. To test these possibilities, we ran a battery of 7
tasks examining word processing in a group of DP cases and controls. One of our
prosopagnosia cases exhibited a severe reading impairment with delayed response
times during reading aloud tasks, but not lexical decision tasks. Overall,
however, we found no evidence of global word processing deficits in DP,
consistent with a dissociation account for face and word processing.
PMID- 28490792
TI - Length effects on the dynamic process of cellular uptake and exocytosis of single
walled carbon nanotubes in murine macrophage cells.
AB - Cellular uptake and exocytosis of SWCNTs are fundamental processes determining
their intracellular concentration and effects. Despite the great potential of
acid-oxidized SWCNTs in biomedical field, understanding of the influencing
factors on these processes needs to be deepened. Here, we quantitatively
investigated uptake and exocytosis of SWCNTs in three lengths-630 (+/-171) nm (L
SWCNTs), 390 (+/-50) nm (M-SWCNTs), and 195 (+/-63) nm (S-MWCNTs) in macrophages.
The results showed that the cellular accumulation of SWCNTs was a length
independent process and non-monotonic in time, with the most SWCNTs (3950
fg/cell) accumulated at 8 h and then intracellular SWCNTs dropped obviously with
time. The uptake rate of SWCNTs decreased with increasing concentration,
suggesting that intracellular SWCNTs accumulation is a saturable process. After
refreshing culture medium, we found increasing SWCNTs in supernatant and
decreasing intracellular SWCNTs over time, confirming the exocytosis occurred.
Selective inhibition of endocytosis pathways showed that the internalization of
SWCNTs involves several pathways, in the order of macropinocytosis> caveolae
mediated endocytosis> clathrin-dependent endocytosis. Intriguingly, clathrin
mediated endocytosis is relatively important for internalizing shorter SWCNTs.
The dynamic processes of SWCNTs uptake and exocytosis and the mechanisms revealed
by this study may render a better understanding on SWCNT toxicity and facilitate
the design of CNT products with mitigated toxicity and desired functions.
PMID- 28490793
TI - Campanile Near-Field Probes Fabricated by Nanoimprint Lithography on the Facet of
an Optical Fiber.
AB - One of the major challenges to the widespread adoption of plasmonic and nano
optical devices in real-life applications is the difficulty to mass-fabricate
nano-optical antennas in parallel and reproducible fashion, and the capability to
precisely place nanoantennas into devices with nanometer-scale precision. In this
study, we present a solution to this challenge using the state-of-the-art
ultraviolet nanoimprint lithography (UV-NIL) to fabricate functional optical
transformers onto the core of an optical fiber in a single step, mimicking the
'campanile' near-field probes. Imprinted probes were fabricated using a custom
built imprinter tool with co-axial alignment capability with sub <100 nm position
accuracy, followed by a metallization step. Scanning electron micrographs confirm
high imprint fidelity and precision with a thin residual layer to facilitate
efficient optical coupling between the fiber and the imprinted optical
transformer. The imprinted optical transformer probe was used in an actual NSOM
measurement performing hyperspectral photoluminescence mapping of standard
fluorescent beads. The calibration scans confirmed that imprinted probes enable
sub-diffraction limited imaging with a spatial resolution consistent with the gap
size. This novel nano-fabrication approach promises a low-cost, high-throughput,
and reproducible manufacturing of advanced nano-optical devices.
PMID- 28490794
TI - Thermally induced micro-motion by inflection in optical potential.
AB - Recent technological progress in a precise control of optically trapped objects
allows much broader ventures to unexplored territory of thermal motion in non
linear potentials. In this work, we exploit an experimental set-up of holographic
optical tweezers to experimentally investigate Brownian motion of a micro
particle near the inflection point of the cubic optical potential. We present two
complementary views on the non-linear Brownian motion. On an ensemble of
stochastic trajectories, we simultaneously determine (i) the detailed short-time
position statistics and (ii) the long-distance first-passage time statistics. We
evaluate specific statistical moment ratios demonstrating strongly non-linear
stochastic dynamics. This is a crucial step towards a possible massive
exploitation of the broad class of complex non-linear stochastic effects with
objects of more complex structure and shape including living ones.
PMID- 28490795
TI - Performances of Kevlar and Polyethylene as radiation shielding on-board the
International Space Station in high latitude radiation environment.
AB - Passive radiation shielding is a mandatory element in the design of an integrated
solution to mitigate the effects of radiation during long deep space voyages for
human exploration. Understanding and exploiting the characteristics of materials
suitable for radiation shielding in space flights is, therefore, of primary
importance. We present here the results of the first space-test on Kevlar and
Polyethylene radiation shielding capabilities including direct measurements of
the background baseline (no shield). Measurements are performed on-board of the
International Space Station (Columbus modulus) during the ALTEA-shield ESA
sponsored program. For the first time the shielding capability of such materials
has been tested in a radiation environment similar to the deep-space one, thanks
to the feature of the ALTEA system, which allows to select only high latitude
orbital tracts of the International Space Station. Polyethylene is widely used
for radiation shielding in space and therefore it is an excellent benchmark
material to be used in comparative investigations. In this work we show that
Kevlar has radiation shielding performances comparable to the Polyethylene ones,
reaching a dose rate reduction of 32 +/- 2% and a dose equivalent rate reduction
of 55 +/- 4% (for a shield of 10 g/cm2).
PMID- 28490796
TI - Degradation mechanisms of silver nanowire electrodes under ultraviolet
irradiation and heat treatment.
AB - We report the degradation mechanisms of the silver nanowire (Ag NW) electrodes
that play a significantly important role in the stability of wearable and
flexible devices. The degradation mechanisms behind the increase in the sheet
resistances of Ag NW electrodes were clarified by investigating the variations in
the structure and the chemical composition of the Ag NW electrodes caused by
ultraviolet irradiation and thermal treatment. While the shapes of the Ag NWs
were affected by melting during the thermal degradation process, the chemical
composition of the polyvinylpyrrolidone protective layer on the surfaces of the
Ag NWs was not changed. Ultraviolet irradiation deformed the shapes of the Ag NWs
because nitrogen or oxygen atoms were introduced to the silver atoms on the
surfaces of the Ag NWs. A graphene-oxide flake was coated on the Ag NW electrodes
by using a simple dipping method to prevent ultraviolet irradiation and ozone
contact with the surfaces of the Ag NWs, and the increase in the sheet resistance
in the graphene-oxide-treated Ag NWs was suppressed. These observations will be
of assistance to researchers trying to find novel ways to improve the stability
of the Ag NW electrodes in next-generation wearable devices.
PMID- 28490797
TI - Action on diabetic macular oedema: achieving optimal patient management in
treating visual impairment due to diabetic eye disease.
AB - This paper identifies best practice recommendations for managing diabetes and
sight-threatening diabetic eye disease. The authors provide an update for
ophthalmologists and allied healthcare professionals on key aspects of diabetes
management, supported by a review of the pertinent literature, and recommend
practice principles for optimal patient management in treating visual impairment
due to diabetic eye disease. In people with diabetes, early optimal glycaemic
control reduces the long-term risk of both microvascular and macrovascular
complications. The authors propose more can and should be done to maximise
metabolic control, promote appropriate behavioural modifications and encourage
timely treatment intensification when indicated to ameliorate diabetes-related
complications. All people with diabetes should be screened for sight-threatening
diabetic retinopathy promptly and regularly. It is shown that attitudes towards
treatment adherence in diabetic macular oedema appear to mirror patients' views
and health behaviours towards the management of their own diabetes. Awareness of
diabetic macular oedema remains low among people with diabetes, who need access
to education early in their disease about how to manage their diabetes to delay
progression and possibly avoid eye-related complications. Ophthalmologists and
allied healthcare professionals play a vital role in multidisciplinary diabetes
management and establishment of dedicated diabetic macular oedema clinics is
proposed. A broader understanding of the role of the diabetes specialist nurse
may strengthen the case for comprehensive integrated care in ophthalmic practice.
The recommendations are based on round table presentations and discussions held
in London, UK, September 2016.
PMID- 28490799
TI - Rare Polyene-polyol Macrolides from Mangrove-derived Streptomyces sp. ZQ4BG.
AB - Bioactive natural products from mangrove-derived actinomycetes are important
sources for discovery of drug lead compounds. In this study, an extract prepared
from culture of an actinomycete Streptomyces sp. ZQ4BG isolated from mangrove
soils was found to have activity in inhibiting proliferation of glioma cells.
Large culture of this mangrove actinomycete in Gause's liquid medium resulted in
isolation of seven novel polyene-polyol macrolides, named as flavofungins III-IX
(3-9), together with known flavofungins I (1) and II (2) and spectinabilin (10).
Structures of these isolated compounds were elucidated by extensive NMR analyses
and HRESIMS data. The stereochemical assignments were achieved by a combination
of NOE information, universal NMR database, and chemical reactions including
preparation of acetonide derivatives and Mosher esters. Flavofungins IV-VIII (4
8) are rare 32-membered polyene-polyol macrolides with a tetrahydrofuran ring,
while flavofungin IX (9) represents the first example of this type of macrolide
with a unique oxepane ring. Flavofungins I (1) and II (2) and spectinabilin (10)
showed anti-glioma and antifungal activities.
PMID- 28490798
TI - Enhancing the Oxidation of Toluene with External Electric Fields: a Reactive
Molecular Dynamics Study.
AB - The effects of external electric field (Efield) on chemical reactions were
studied with the reactive molecular dynamics (ReaxFF MD) simulations by using the
oxidation of toluene as a model system. We observed that Efields may greatly
enhance the oxidation rate of toluene. The initial reaction time of toluene is
also reduced remarkably in Efields. A stronger Efield leads to a faster oxidation
rate of toluene. Further studies reveal that the applying of a Efield may result
in the oxidation of toluene at 2100 K which is otherwise not able to happen when
the Efield is not present. The oxidation rate of toluene at 2100 K in a Efield is
comparable with the oxidation rate of toluene at 2900 K when the Efield is not
applied. In addition, Efields were observed to significantly enhance the
occurrence of the initial radical generation for different pathways of toluene
oxidation but they do not seem to favor any of the pathways. Finally, Efields do
not seem to enhance the polarization of toluene during its transition state,
which suggests that a polarizable charge equilibration method (PQEq) method might
be needed to take the effects of Efields into consideration.
PMID- 28490800
TI - The formation mechanism of tear strips on stretched Ti-22Al-25Nb alloy sheets.
AB - This paper reports the presence of tear strips on the surface of a Ti-22Al-25Nb
alloy sheet stretched at 960 degrees C. The test piece reveals a "bamboo"-shaped
pattern on its surface, which severely affects the quality of the alloy.
Microstructure analysis indicates that the formation mechanism of the tear strip
is related to both the rich alpha2 phase layer and the interfacial B2 phase
dynamic recrystallization layer between the alpha2 phase layer and the substrate
metal.
PMID- 28490801
TI - Dendritic cells provide a therapeutic target for synthetic small molecule
analogues of the parasitic worm product, ES-62.
AB - ES-62, a glycoprotein secreted by the parasitic filarial nematode
Acanthocheilonema viteae, subverts host immune responses towards anti
inflammatory phenotypes by virtue of covalently attached phosphorylcholine (PC).
The PC dictates that ES-62 exhibits protection in murine models of inflammatory
disease and hence a library of drug-like PC-based small molecule analogues (SMAs)
was synthesised. Four sulfone-containing SMAs termed 11a, 11e, 11i and 12b were
found to reduce mouse bone marrow-derived dendritic cell (DC) pathogen-associated
molecular pattern (PAMP)-induced pro-inflammatory cytokine production, inhibit NF
kappaB p65 activation, and suppress LPS-induced up-regulation of CD40 and CD86.
Active SMAs also resulted in a DC phenotype that exhibited reduced capacity to
prime antigen (Ag)-specific IFN-gamma production during co-culture with naive
transgenic TCR DO.11.10 T cells in vitro and reduced their ability, following
adoptive transfer, to prime the expansion of Ag-specific T lymphocytes,
specifically TH17 cells, in vivo. Consistent with this, mice receiving DCs
treated with SMAs exhibited significantly reduced severity of collagen-induced
arthritis and this was accompanied by a significant reduction in IL-17+ cells in
the draining lymph nodes. Collectively, these studies indicate that drug-like
compounds that target DCs can be designed from parasitic worm products and
demonstrate the potential for ES-62 SMA-based DC therapy in inflammatory disease.
PMID- 28490802
TI - Transcriptome analysis of dominant-negative Brd4 mutants identifies Brd4-specific
target genes of small molecule inhibitor JQ1.
AB - The bromodomain protein Brd4 is an epigenetic reader and plays a critical role in
the development and maintenance of leukemia. Brd4 binds to acetylated histone
tails and activates transcription by recruiting the positive elongation factor P
TEFb. Small molecule inhibitor JQ1 competitively binds the bromodomains of Brd4
and displaces the protein from acetylated histones. However, it remains unclear
whether genes targeted by JQ1 are mainly regulated by Brd4 or by other
bromodomain proteins such as Brd2 and Brd3. Here, we describe anti-proliferative
dominant-negative Brd4 mutants that compete with the function of distinct Brd4
domains. We used these Brd4 mutants to compare the Brd4-specific transcriptome
with the transcriptome of JQ1-treated cells. We found that most JQ1-regulated
genes are also regulated by dominant-negative Brd4 mutants, including the mutant
that competes with the P-TEFb recruitment function of Brd4. Importantly, JQ1 and
dominant-negative Brd4 mutants regulated the same set of target genes of c-Myc, a
key regulator of the JQ1 response in leukemia cells. Our results suggest that
Brd4 mediates most of the anti-cancer effects of JQ1 and that the major function
of Brd4 in this process is the recruitment of P-TEFb. In summary, our studies
define the molecular targets of JQ1 in more detail.
PMID- 28490803
TI - Effects of smoking and smoking abstinence on spatial vision in chronic heavy
smokers.
AB - Cigarette smoke is a complex chemical mixture, involving health-damaging
components such as carbon monoxide, ammonia, pyridine, toluene and nicotine.
While cognitive functions have been well documented in heavy smokers, spatial
vision has been less characterized. In the article, we investigated smoking
effects through contrast sensitivity function (CSF), a rigorous procedure that
measures the spatial vision. Data were recorded from 48 participants, a group of
non-smokers (n = 16), a group of chronic and heavy cigarette smokers (n = 16) and
deprived smokers (n = 16); age range 20-45 years. Sinewave gratings with spatial
frequencies ranging from 0.25 to 20 cycles per degree were used. All subjects
were free from any neurological disorder, identifiable ocular disease and had
normal acuity. No abnormalities were detected in the fundoscopic examination and
in the optical coherence tomography exam. Contrary to expectations, performance
on CSF differed between groups. Both smokers and deprived smokers presented a
loss of contrast sensitivity compared to non-smokers. Post-hoc analyses suggest
that deprived smokers were less sensitive at all spatial frequencies. These
results suggest that not only chronic exposure to cigarette compounds but also
withdrawal from nicotine affected spatial vision. This highlights the importance
of understanding diffuse effects of smoking compounds on visual spatial
processing.
PMID- 28490804
TI - Epitaxial growth of Cu(001) thin films onto Si(001) using a single-step HiPIMS
process.
AB - We report on a new route to grow epitaxial copper (Cu) ultra-thin films (up to
150 nm thick) at ambient temperature on Si(001) wafers covered with native oxide
without any prior chemical etching or plasma cleaning of the substrate. It
consists of a single-step deposition process using high power impulse magnetron
sputtering (HiPIMS) and substrate biasing. For a direct current (DC) substrate
bias voltage of -130 V, Cu/Si heteroepitaxial growth is achieved by HiPIMS
following the Cu(001) [100]//Si(001) [110] orientation, while under the same
average deposition conditions, but using conventional DC magnetron sputtering,
polycrystalline Cu films with [111] preferred orientation are deposited. In
addition, the intrinsic stress has been measured in situ during growth by real
time monitoring of the wafer curvature. For this particular HiPIMS case, the
stress is slightly compressive (-0.1 GPa), but almost fully relaxes after growth
is terminated. As a result of epitaxy, the Cu surface morphology exhibits a
regular pattern consisting of square-shaped mounds with a lateral size of
typically 150 nm. For all samples, X-ray diffraction pole figures and
scanning/transmission electron microscopy reveal the formation of extensive
twinning of the Cu {111} planes.
PMID- 28490805
TI - A Skint6 allele potentially contributes to mouse lupus.
AB - Our previous study uncovered that the overlapping region of murine lupus
susceptibility Sle2c1rec1a and Sle2c1rec1d subloci is strongly associated with
lymphadenopathy and systemic autoimmunity. In order to identify the specific
candidate gene, we generated a novel shorter recombinant, named as Sle2c1re1d1
(rec1d1), from Sle2c1rec1d sublocus (rec1d). The rec1d1 interval corresponds
precisely to the overlapping region of Sle2c1rec1a and Sle2c1rec1d subloci.
Functionally, this rec1d1 sublocus showed a strong epistatic interaction with
lpr, similar to that seen with Sle2c1rec1a or.Sle2c1rec1d. The Skint6 gene in the
red1d1 interval was identified to have a point mutation, which inserts a
premature stop codon and converts the membrane Skint6 protein into a truncated
secretory peptide. However, other protein-coding genes in the rec1d1 interval
have no mutation in exon sequence. The heterozygous rec1d1 interval in B6.lpr
demonstrates exacerbated autoimmunity. For example, non-hematopoietic stem cell
derived cells of the B6.Sle2c1rec1d1.lpr mice promote T-cell proliferation in
vivo. These findings led us to conclude that the Skint6 variant in the rec1d1
interval is the most likely causative gene of mouse lupus.
PMID- 28490807
TI - Zeylenone, a naturally occurring cyclohexene oxide, inhibits proliferation and
induces apoptosis in cervical carcinoma cells via PI3K/AKT/mTOR and MAPK/ERK
pathways.
AB - There is a strong rationale to therapeutically target the PI3K/Akt/mTOR and
MAPK/ERK pathways in cervical carcinoma since they are highly deregulated in this
disease. Previous study by our group have demonstrated that Zeylenone (Zey)
exhibited strong suppressive activity on PI3K/AKT/mTOR and MAPK/ERK signaling,
providing a foundation to investigate its antitumor activity in cervical
carcinoma. Herein, the present study aimed to investigate suppressive effect of
Zey on HeLa and CaSki cells, and further explore the underlying mechanisms. Cells
were treated with Zey for indicated time, followed by measuring its effects on
cell viability, colony formation, cell cycle, cell apoptosis, and signal
pathways. In vivo antitumor activity of Zey was then assessed with nude
xenografts. We found that Zey substantially suppressed cell proliferation,
induced cell cycle arrest, and increased cell apoptosis, accompanied by increased
production of ROS, decreased mitochondrial membrane potential, activated caspase
apoptotic cascade, and attenuated PI3K/Akt/mTOR and MAPK/ERK pathways.
Additionally, in vivo experiments showed that Zey exerted good antitumor efficacy
against HeLa bearing mice models via decreasing levels of p-PI3K and p-ERK.
Collectively, these data clearly demonstrated the antitumor activity of Zey in
cervical carcinoma cells, which is most likely via the regulation of
PI3K/Akt/mTOR and MAPK/ERK pathways.
PMID- 28490806
TI - Quantification of blood-brain barrier permeability by dynamic contrast-enhanced
NIRS.
AB - The blood-brain barrier (BBB) is integral to maintaining a suitable
microenvironment for neurons to function properly. Despite its importance, there
are no bedside methods of assessing BBB disruption to help guide management of
critical-care patients. The aim of this study was to demonstrate that dynamic
contrast-enhanced (DCE) near-infrared spectroscopy (NIRS) can quantify the
permeability surface-area product (PS) of the BBB. Experiments were conducted in
rats in which the BBB was opened by image-guided focused ultrasound. DCE-NIRS
data were acquired with two dyes of different molecular weight, indocyanine green
(ICG, 67 kDa) and 800CW carboxylate (IRDye, 1166 Da), and PS maps were generated
by DCE computer tomography (CT) for comparison. Both dyes showed a strong
correlation between measured PS values and sonication power (R2 = 0.95 and 0.92
for ICG and IRDye respectively), and the PS values for IRDye were in good
agreement with CT values obtained with a contrast agent of similar molecular
weight. These proof-of-principle experiments demonstrate that DCE NIRS can
quantify BBB permeability. The next step in translating this method to critical
care practice will be to adapt depth sensitive methods to minimize the effects of
scalp contamination on NIRS PS values.
PMID- 28490808
TI - Dendritic Cell-derived Extracellular Vesicles mediate Mesenchymal Stem/Stromal
Cell recruitment.
AB - Orchestration of bone repair processes requires crosstalk between different cell
populations, including immune cells and mesenchymal stem/stromal cells (MSC).
Extracellular vesicles (EV) as mediators of these interactions remain vastly
unexplored. Here, we aimed to determine the mechanism of MSC recruitment by
Dendritic Cells (DC), hypothesising that it would be mediated by EV. Primary
human DC-secreted EV (DC-EV), isolated by ultracentrifugation, were characterized
for their size, morphology and protein markers, indicating an enrichment in
exosomes. DC-EV were readily internalized by human bone marrow-derived MSC,
without impacting significantly their proliferation or influencing their
osteogenic/chondrogenic differentiation. Importantly, DC-EV significantly and
dose-dependently promoted MSC recruitment across a transwell system and enhanced
MSC migration in a microfluidic chemotaxis assay. DC-EV content was analysed by
chemokine array, indicating the presence of chemotactic mediators. Osteopontin
and matrix metalloproteinase-9 were confirmed inside EV. In summary, DC-EV are
naturally loaded with chemoattractants and can contribute to cell recruitment,
thus inspiring the development of new tissue regeneration strategies.
PMID- 28490809
TI - Hepatic estrogen receptor alpha is critical for regulation of gluconeogenesis and
lipid metabolism in males.
AB - Impaired estrogens action is associated with features of the metabolic syndrome
in animal models and humans. We sought to determine whether disruption of hepatic
estrogens action in adult male mice could recapitulate aspects of the metabolic
syndrome to understand the mechanistic basis for the phenotype. We found 17beta
estradiol (E2) inhibited hepatic gluconeogenic genes such as phosphoenolpyruvate
carboxykinase 1 (Pck-1) and glucose 6-phosphatase (G6Pase) and this effect was
absent in mice lacking liver estrogen receptor alpha (Esr1) (LERKO mice). Male
LERKO mice displayed elevated hepatic gluconeogenic activity and fasting
hyperglycemia. We also observed increased liver lipid deposits and triglyceride
levels in male LERKO mice, resulting from increased hepatic lipogenesis as
reflected by increased mRNA levels of fatty acid synthase (Fas) and acetyl-CoA
carboxylase (Acc1). ChIP assay demonstrated estradiol (E2) induced ESR1 binding
to Pck-1, G6Pase, Fas and Acc1 promoters. Metabolic phenotyping demonstrated both
basal metabolic rate and feeding were lower for the LERKO mice as compared to
Controls. Furthermore, the respiratory exchange rate was significantly lower in
LERKO mice than in Controls, suggesting an increase in lipid oxidation. Our data
indicate that hepatic E2/ESR1 signaling plays a key role in the maintenance of
gluconeogenesis and lipid metabolism in males.
PMID- 28490810
TI - Establishment of induced pluripotent stem cells from normal B cells and inducing
AID expression in their differentiation into hematopoietic progenitor cells.
AB - B cell derived induced pluripotent stem cells (BiPSCs) were recently established
from peripheral blood B cells by the simultaneous transfection of Yamanaka
factors (Oct3/4, Sox2, Klf4, c-Myc) and C/EBPalpha using a Sendai virus vector.
Here, using a different method, we established BiPSCs with immunoglobulin heavy
chain (IgH) gene rearrangement from normal B cells purified from lymph nodes. The
critical points of our method are pre-stimulation of B cells with IL-21 and CD40
ligand (CD40L), followed by consecutive transfection of highly concentrated
Yamanaka factors using a retroviral vector. Following each transfection the cells
were centrifuged onto a retronectin coated plate and the activated by IL-4, IL-2,
and CD40L. Furthermore, we established BiPSCs (BiPSC-A) in which activation
induced cytidine deaminase (AID) could be induced using the doxycycline
controlled. Both the parental BiPSC and BiPSC-A showed the capability of
differentiating into hematopoietic progenitor cells (HPCs) based on confirmation
of CD34 expression and colony-formation from CD34-positive cells. The findings
that BiPSC-A can differentiate into HPCs suggest that there is a possibility that
induction of AID expression would result in chromosomal translocations in the
process of differentiation from BiPSCs, and therefore that these BiPSCs could be
useful in elucidating the tumor origin of abnormal B cells in myelomagenesis.
PMID- 28490811
TI - High efficacy and safety of low-dose CD19-directed CAR-T cell therapy in 51
refractory or relapsed B acute lymphoblastic leukemia patients.
AB - Refractory or relapsed B lymphoblastic leukemia (B-ALL) patients have a dismal
outcome with current therapy. We treated 42 primary refractory/hematological
relapsed (R/R) and 9 refractory minimal residual disease by flow cytometry (FCM
MRD+) B-ALL patients with optimized second generation CD19-directed CAR-T cells.
The CAR-T-cell infusion dosages were initially ranged from 0.05 to 14 * 105/kg
and were eventually settled at 1 * 105/kg for the most recent 20 cases. 36/40
(90%) evaluated R/R patients achieved complete remission (CR) or CR with
incomplete count recovery (CRi), and 9/9 (100%) FCM-MRD+ patients achieved MRD-.
All of the most recent 20 patients achieved CR/CRi. Most cases only experienced
mild to moderate CRS. 8/51 cases had seizures that were relieved by early
intervention. Twenty three of twenty seven CR/CRi patients bridged to allogeneic
hematopoietic stem cell transplantation (allo-HCT) remained in MRD- with a median
follow-up time of 206 (45-427) days, whereas 9 of 18 CR/CRi patients without allo
HCT relapsed. Our results indicate that a low CAR-T-cell dosage of 1 * 105/kg, is
effective and safe for treating refractory or relapsed B-ALL, and subsequent allo
HCT could further reduce the relapse rate.
PMID- 28490812
TI - HDAC3 regulates DNMT1 expression in multiple myeloma: therapeutic implications.
AB - Epigenetic signaling pathways are implicated in tumorigenesis and therefore
histone deacetylases (HDACs) represent novel therapeutic targets for cancers,
including multiple myeloma (MM). Although non-selective HDAC inhibitors show anti
MM activities, unfavorable side effects limit their clinical efficacy. Isoform-
and/or class-selective HDAC inhibition offers the possibility to maintain
clinical activity while avoiding adverse events attendant to broad non-selective
HDAC inhibition. We have previously reported that HDAC3 inhibition, either by
genetic knockdown or selective inhibitor BG45, abrogates MM cell proliferation.
Here we show that knockdown of HDAC3, but not HDAC1 or HDAC2, as well as BG45,
downregulate expression of DNA methyltransferase 1 (DNMT1) mediating MM cell
proliferation. DNMT1 expression is regulated by c-Myc, and HDAC3 inhibition
triggers degradation of c-Myc protein. Moreover, HDAC3 inhibition results in
hyperacetylation of DNMT1, thereby reducing the stability of DNMT1 protein.
Combined inhibition of HDAC3 and DNMT1 with BG45 and DNMT1 inhibitor 5
azacytidine (AZA), respectively, triggers synergistic downregulation of DNMT1,
growth inhibition and apoptosis in both MM cell lines and patient MM cells.
Efficacy of this combination treatment is confirmed in a murine xenograft MM
model. Our results therefore provide the rationale for combination treatment
using HDAC3 inhibitor with DNMT1 inhibitor to improve patient outcome in MM.
PMID- 28490813
TI - Leptin receptor antagonism of iNKT cell function: a novel strategy to combat
multiple myeloma.
AB - A hallmark of bone marrow changes with aging is the increase in adipocyte
composition, but how this impacts development of multiple myeloma (MM) is
unknown. Here, we report the role of the adipokine leptin as master regulator of
anti-myeloma tumor immunity by modulating the invariant natural killer T (iNKT)
cell function. A marked increase in serum leptin levels and leptin receptor (LR)
expression on iNKT cells in MM patients and the 5T33 murine MM model was
observed. MM cells and leptin synergistically counteracted anti-tumor
functionality of both murine and human iNKT cells. In vivo blockade of LR
signaling combined with iNKT stimulation resulted in superior anti-tumor
protection. This was linked to persistent IFN-gamma secretion upon repeated iNKT
cell stimulation and a restoration of the dynamic antigen-induced motility arrest
as observed by intravital microscopy, thereby showing alleviation of iNKT cell
anergy. Overall our data reveal the LR axis as novel therapeutic target for
checkpoint inhibition to treat MM.
PMID- 28490814
TI - Matrix elasticity-modified scaffold loaded with SDF-1alpha improves the in situ
regeneration of segmental bone defect in rabbit radius.
AB - The effectiveness of stem-cell based therapy has been hampered by the limited
availability of stem cell sources, immune rejection, and difficulties in clinical
adoption and regulatory approval. These obstacles can be partially circumvented
by using in situ tissue engineering that recruits the endogenous stem/progenitor
cells and provides cues to direct stem cell phenotype. Here, decellularized bone
scaffold is mechanically modified by coating of collagen (Col)/hydroxyapatite
(HA) mixture with optimal ratio and loaded with chemokine stromal cell-derived
factor-1alpha (SDF-1alpha), in which endogenous stem cell recruitment can be
improved by chemokine and stem cell fate can be regulated by matrix elasticity of
the scaffold. This study shows that mesenchymal stem cells (MSCs) osteogenesis in
vitro was enhanced by matrix elasticity and SDF-1alpha, and endogenous MSCs
recruitment in subcutaneous implantation of rat was increased by the release of
SDF-1alpha from the scaffold, and bone regeneration in rabbit large bone defect
model was significantly improved by matrix elasticity and SDF-1alpha. In short,
this study provides a new insight for developing novel engineered cell-free bone
substitutes by mechanical modification for tissue engineering and regenerative
medicine.
PMID- 28490815
TI - Flexible and Self-Healing Aqueous Supercapacitors for Low Temperature
Applications: Polyampholyte Gel Electrolytes with Biochar Electrodes.
AB - A flexible and self-healing supercapacitor with high energy density in low
temperature operation was fabricated using a combination of biochar-based
composite electrodes and a polyampholyte hydrogel electrolyte. Polyampholytes, a
novel class of tough hydrogel, provide self-healing ability and mechanical
flexibility, as well as low temperature operation for the aqueous electrolyte.
Biochar is a carbon material produced from the low-temperature pyrolysis of
biological wastes; the incorporation of reduced graphene oxide conferred
mechanical integrity and electrical conductivity and hence the electrodes are
called biochar-reduced-graphene-oxide (BC-RGO) electrodes. The fabricated
supercapacitor showed high energy density of 30 Wh/kg with ~90% capacitance
retention after 5000 charge-discharge cycles at room temperature at a power
density of 50 W/kg. At -30 degrees C, the supercapacitor exhibited an energy
density of 10.5 Wh/kg at a power density of 500 W/kg. The mechanism of the low
temperature performance excellence is likely to be associated with the concept of
non-freezable water near the hydrophilic polymer chains, which can motivate
future researches on the phase behaviour of water near polyampholyte chains. We
conclude that the combination of the BC-RGO electrode and the polyampholyte
hydrogel electrolyte is promising for supercapacitors for flexible electronics
and for low temperature environments.
PMID- 28490816
TI - Rethinking Sexual Citizenship.
AB - Over the last two decades sexuality has emerged as a key theme in debates about
citizenship, leading to the development of the concept of sexual citizenship.
This article reviews this literature and identifies four main areas of critical
framing: work that contests the significance of sexuality to citizenship;
critiques that focus on the possibilities and limitations of mobilising the
language of citizenship in sexual politics; analyses of sexual citizenship in
relation to nationalisms and border making; and literature that critically
examines western constructions of sexuality and sexual politics underpinning
understandings of sexual citizenship. In order to progress the field
theoretically, the article seeks to extend critiques of sexual citizenship
focusing on two key aspects of its construction: the sexual citizen-subject and
spaces of sexual citizenship. It argues for a critical rethink that encompasses a
de-centring of a 'western-centric' focus in order to advance understandings of
how sexual citizenship operates both in the Global North and South.
PMID- 28490817
TI - Transphobic 'Honour'-Based Abuse: A Conceptual Tool.
AB - This article proposes that an understanding of transphobic 'honour'-based abuse
can be employed as a conceptual tool to explore trans people's experiences of
familial abuse. This conception has evolved by connecting a sociology of shame,
Goffman's work on stigma and 'honour'-based ideology. The discussion draws upon
findings of a qualitative study which explored trans people's experiences of
domestic violence and abuse. Narrative interviews were undertaken with 15 trans
people who had either experienced abuse or whose perceptions were informed
experientially through their support of others. Transcripts were analysed using
the Listening Guide. Findings indicate that trans people can experience abuse as
a result of a family's perceptions of shame and stigma. This article offers a
novel way of conceptualising trans people's experiences of family-based abuse,
but it also holds potential for understanding other relational contexts, for
example, those of intimate partnerships.
PMID- 28490819
TI - Testing Times: The Place of the Citizenship Test in the UK Immigration Regime and
New Citizens' Responses to it.
AB - Citizenship tests are designed to ensure that new citizens have the knowledge
required for successful 'integration'. This article explores what those who have
taken the test thought about its content. It argues that new citizens had high
levels of awareness of debates about immigration and anti-immigration sentiment.
Considering new citizens' views of the test, the article shows how many of them
are aware of the role of the test in reassuring existing citizens of their
fitness to be citizens. However, some new citizens contest this positioning in
'acts of citizenship' where they assert claims to citizenship which are not
necessarily those constructed by the state and implied in the tests. The article
will argue that the tests and the nature of the knowledge required to pass them
serve to retain new citizens in a position of less-than-equal citizenship which
is at risk of being discursively (if less often legally) revoked.
PMID- 28490818
TI - The Structural Invisibility of Outsiders: The Role of Migrant Labour in the Meat
Processing Industry.
AB - This article examines the role of migrant workers in meat-processing factories in
the UK. Drawing on materials from mixed methods research in a number of case
study towns across Wales, we explore the structural and spatial processes that
position migrant workers as outsiders. While state policy and immigration
controls are often presented as a way of protecting migrant workers from work
based exploitation and ensuring jobs for British workers, our research highlights
that the situation 'on the ground' is more complex. We argue that 'self
exploitation' among the migrant workforce is linked to the strategies of
employers and the organisation of work, and that hyper-flexible work patterns
have reinforced the spatial and social invisibilities of migrant workers in this
sector. While this creates problems for migrant workers, we conclude that it is
beneficial to supermarkets looking to supply consumers with the regular supply of
cheap food to which they have become accustomed.
PMID- 28490820
TI - The End of Hypergamy: Global Trends and Implications.
AB - The gender gap in education that has long favored men has reversed for young
adults in almost all high and middle-income countries. In 2010, the proportion of
women aged 25-29 with a college education was higher than that of men in more
than 139 countries which altogether represent 86% of the world's population.
According to recent population forecasts, women will have more education than men
in nearly every country in the world by 2050, with the exception of only a few
African and West Asian countries (KC et al. 2010). The reversal of the gender gap
in education has major implications for the composition of marriage markets,
assortative mating, gender equality, and marital outcomes such as divorce and
childbearing (Van Bavel 2012). In this work, we focus on its implications for
trends in assortative mating and, in particular, for educational hypergamy: the
pattern in which husbands have more education than their wives. This represents a
substantial update to previous studies (Esteve et al. 2012) in terms of the
number of countries and years included in the analysis. We present findings from
an almost comprehensive world-level analysis using census and survey microdata
from 420 samples and 120 countries spanning from 1960 to 2011, which allow us to
assert that the reversal of the gender gap in education is strongly associated
with the end of hypergamy and increases in hypogamy (wives have more education
that their husbands). We not only provide near universal evidence of this trend
but extend our analysis to consider the implications of the end of hypergamy for
family dynamics, outcomes and gender equality. We draw on European microdata to
examine whether women are more likely to be the breadwinners when they marry men
with lower education than themselves and discuss recent research regarding
divorce risks among hypogamous couples. We close our analysis with an examination
of attitudes about women earning more money than their husbands and about the
implications for children when a woman works for pay.
PMID- 28490821
TI - Who support open access publishing? Gender, discipline, seniority and other
factors associated with academics' OA practice.
AB - This paper presents the findings from a survey study of UK academics and their
publishing behaviour. The aim of this study is to investigate academics'
attitudes towards and practice of open access (OA) publishing. The results are
based on a survey study of academics at 12 Russell Group universities, and
reflect responses from over 1800 researchers. This study found that whilst most
academics support the principle of making knowledge freely available to everyone,
the use of OA publishing among UK academics was still limited despite relevant
established OA policies. The results suggest that there were differences in the
extent of OA practice between different universities, academic disciplines, age
and seniorities. Academics' use in OA publishing was also related to their
awareness of OA policy and OA repositories, their attitudes towards the
importance of OA publishing and their belief in OA citation advantage. The
implications of these findings are relevant to the development of strategies for
the implementation of OA policies.
PMID- 28490822
TI - How to reduce the number of rating scale items without predictability loss?
AB - Rating scales are used to elicit data about qualitative entities (e.g., research
collaboration). This study presents an innovative method for reducing the number
of rating scale items without the predictability loss. The "area under the
receiver operator curve method" (AUC ROC) is used. The presented method has
reduced the number of rating scale items (variables) to 28.57% (from 21 to 6)
making over 70% of collected data unnecessary. Results have been verified by two
methods of analysis: Graded Response Model (GRM) and Confirmatory Factor Analysis
(CFA). GRM revealed that the new method differentiates observations of high and
middle scores. CFA proved that the reliability of the rating scale has not
deteriorated by the scale item reduction. Both statistical analysis evidenced
usefulness of the AUC ROC reduction method.
PMID- 28490823
TI - International patent families: from application strategies to statistical
indicators.
AB - This paper provides an in-depth analysis of the characteristics of international
patent families, including their domestic component. We exploit a relatively
under-studied feature of patent families, namely the number of patents covering
the same invention within a given jurisdiction. Using this information, we
highlight common patterns in the structure of international patent families,
which reflect both the patenting strategies of innovators and the peculiarities
of the different patent systems. While the literature has extensively used family
size, i.e. the number of countries in which a given invention is protected, as a
measure of patent value, our results suggest that the number of patent filings in
the priority country within a patent family as well as the timespan between the
first and last filings within a family are other insightful indicators of the
value of patented innovations.
PMID- 28490824
TI - Patent information retrieval: approaching a method and analysing nanotechnology
patent collaborations.
AB - Many challenges still remain in the processing of explicit technological
knowledge documents such as patents. Given the limitations and drawbacks of the
existing approaches, this research sets out to develop an improved method for
searching patent databases and extracting patent information to increase the
efficiency and reliability of nanotechnology patent information retrieval process
and to empirically analyse patent collaboration. A tech-mining method was applied
and the subsequent analysis was performed using Thomson data analyser software.
The findings show that nations such as Korea and Japan are highly collaborative
in sharing technological knowledge across academic and corporate organisations
within their national boundaries, and China presents, in some cases, a great
illustration of effective patent collaboration and co-inventorship. This study
also analyses key patent strengths by country, organisation and technology.
PMID- 28490825
TI - Citation-based clustering of publications using CitNetExplorer and VOSviewer.
AB - Clustering scientific publications in an important problem in bibliometric
research. We demonstrate how two software tools, CitNetExplorer and VOSviewer,
can be used to cluster publications and to analyze the resulting clustering
solutions. CitNetExplorer is used to cluster a large set of publications in the
field of astronomy and astrophysics. The publications are clustered based on
direct citation relations. CitNetExplorer and VOSviewer are used together to
analyze the resulting clustering solutions. Both tools use visualizations to
support the analysis of the clustering solutions, with CitNetExplorer focusing on
the analysis at the level of individual publications and VOSviewer focusing on
the analysis at an aggregate level. The demonstration provided in this paper
shows how a clustering of publications can be created and analyzed using freely
available software tools. Using the approach presented in this paper,
bibliometricians are able to carry out sophisticated cluster analyses without the
need to have a deep knowledge of clustering techniques and without requiring
advanced computer skills.
PMID- 28490826
TI - Understanding and Assessing Word Comprehension.
AB - The Intermodal Preferential Looking (IPL) task was developed to assess
comprehension in infants and toddlers. We extend this methodology to examine word
comprehension in preschool children using two measures: proportion of looking
time to target (LTT) and longest look (LL) to target. Children (3-6 years) were
tested with the IPL for comprehension of nouns, verbs, and adjectives. Both LTT
and LL scores showed that, across all ages, eye gaze to the target word increased
from baseline to test; there were higher scores for nouns compared to verbs and
adjectives. We also compare IPL performance to scores on a standardized test of
receptive vocabulary (PPVT-4). Correlations with PPVT-4 scores were stronger for
LTT than LL measures. The IPL may provide an alternative method for assessing
word comprehension in preschool children with behavioral limitations.
PMID- 28490828
TI - Family Trajectories and Well-being of Children Born to Lone Mothers in the UK.
AB - We investigate how lone mothers' heterogeneity in partnership trajectories is
associated with children's well-being. We use data from the Millennium Cohort
Study, which follows a large sample of children born in the UK in 2000-2002. We
divide children who were born to lone mothers into four groups based on their
mothers' partnership trajectories between birth and age seven, which cover more
than 80% of these children's family experiences. We then analyse how these
trajectories are associated with markers of health, cognitive and socio-emotional
outcomes measured at around age seven. We find that compared to the children that
live continuously with lone mothers, children whose biological father stably
joined the household have better cognitive and socio-emotional outcomes. In
contrast, children in trajectories characterised by living with a stepfather or
who experienced biological father joining in the family followed by biological
parents' dissolution had outcomes similar to children living continuously with
lone mothers. The results underscore the importance of treating children born to
lone mothers as a heterogeneous category.
PMID- 28490827
TI - Sexual Risk Among African American Women: Psychological Factors and the Mediating
Role of Social Skills.
AB - Prior research demonstrates a positive association between mental health problems
and sexual risk for African American women. Using the social skills deficit
hypothesis, we proposed that social skills mediate this relationship. African
American women (n = 557, M age = 20.58) completed measures of depression, stress,
emotional dysregulation, sexual risk behaviors, and perceptions of their social
skills with their primary sexual partner. Social skills mediated the link between
the mental health assessments and a composite sexual risk index. Theoretical
implications of extending the social skill deficit hypothesis are discussed as
well as implications for interventions.
PMID- 28490829
TI - Does Living in a Fatherless Household Compromise Educational Success? A
Comparative Study of Cognitive and Non-cognitive Skills.
AB - This study addresses the relationship between various family forms and the level
of cognitive and non-cognitive skills among 15- to 16-year-old students. We
measure cognitive skills using standardized scores in mathematics; non-cognitive
abilities are captured by a composite measure of internal locus of control
related to mathematics. A particular focus lies on father absence although we
also examine the role played by co-residence with siblings and grandparents. We
use cross-nationally comparable data on students participating in the Programme
for International Student Assessment's release for 2012. By mapping inequalities
by family forms across 33 developed countries, this study provides robust cross
country comparable evidence on the relationship of household structure with both
cognitive and non-cognitive skills. The study produces three key results: first,
the absence of fathers from the household as well as co-residence with
grandparents is associated with adverse outcomes for children in virtually all
developed countries. Second, this is generally true in terms of both cognitive
and non-cognitive skills, although the disadvantage connected to both family
forms is notably stronger in the former than in the latter domain. Finally, there
is marked cross-national diversity in the effects associated with the presence in
the household of siblings and especially grandparents which furthermore differs
across the two outcomes considered.
PMID- 28490830
TI - Explaining Conflicting Results in Research on the Heterogeneous Effects of
Parental Separation on Children's Educational Attainment According to Social
Background.
AB - In recent years, researchers have become increasingly interested in how the
effects of parental separation on children's educational attainment vary with
social background. On the one hand, parents with more resources might be better
able to prevent possible adverse events like separation to affect their
children's outcomes. On the other hand, children from higher social backgrounds
might have more resources to lose from a parental separation. A wide range of
empirical studies on the issue have come to inconsistent conclusions, with
support found for both perspectives. The aim of this paper is to monitor the
influence of methodological and operational choices on the different results
observed across studies. We focus on aspects such as the operationalization of
key variables, the measurement of inequality in absolute and relative terms and
the different strategies used to address endogeneity. We study the effects of
parental separation on educational attainment for a cohort of British children
born in 1970 and find that conclusions change depending on whether social
background is measured using the mother's or father's characteristics and whether
relative or absolute differences between groups are considered. Results are
relatively insensitive to the operationalization of dependent variables and the
treatment of missing data. When using data from Understanding Society instead of
the British Cohort Study, results also did not change. We reflect on how these
findings can explain the contradictory results from earlier studies on the topic,
and how heterogeneity in the effects of parental separation by socio-economic
background should be interpreted.
PMID- 28490831
TI - Parental Separation and School Performance Among Children of Immigrant Mothers in
Sweden.
AB - Immigration and family change are two demographic processes that have changed the
face of European societies and are associated with inequalities in child
outcomes. Yet there is little research outside the USA on whether the effects of
family dynamics on children's life chances vary by immigrant background. We asked
whether the effect of parental separation on educational achievement varies
between immigrant backgrounds (ancestries) in Sweden. We used Swedish population
register data on two birth cohorts (born in 1995 and 1996) of Swedish-born
children and analyzed parental separation penalties on grade sums and non-passing
grades (measured at ninth grade) across ten ancestry groups, defined by the
mother's country of birth. We found that the parental separation effects vary
across ancestries, being weakest among children with Chilean-born mothers and
strongest among children with mothers born in Bosnia and Herzegovina. In general,
the effects were weaker in groups in which parental separation was a more common
experience.
PMID- 28490832
TI - Gender Differences in Depressive Symptoms Among HIV-Positive Concordant and
Discordant Heterosexual Couples in China.
AB - HIV seropositive individuals and their heterosexual partners/spouses, either
seropositive or seronegative, are facing several mental health challenges. The
objective of this study was to examine gender differences in depressive symptoms
among HIV-positive concordant and HIV-discordant couples. We identified
heterosexual couples from participants of a randomized controlled trial conducted
in Anhui province, China. A total of 265 couples, comprising 129 HIV+ male/HIV-
female couples, 98 HIV- male/HIV+ female couples, and 38 HIV-positive concordant
couples, were included in the analyses. We collected data using the computer
assisted personal interview method. We used a linear mixed-effects regression
model to assess whether gender differences in depressive symptoms varied across
couple types. HIV-positive women reported a significantly higher level of
depressive symptoms than their partners/spouses. HIV-positive women with HIV
positive partners had higher depressive symptoms than those with HIV-negative
partners, whereas HIV-positive men reported similar levels of depressive symptoms
regardless of their partners' serostatus. Among the concordant couples, those
with the highest annual family income showed the greatest gender differences in
depressive symptoms. We suggest that family interventions should be gender- and
couple-type specific and that mental health counseling is warranted not only for
HIV-positive women but also for HIV-negative women in an HIV-affected
relationship.
PMID- 28490833
TI - ASSESSING THE RELATION BETWEEN FLEXIBILITY IN EMOTIONAL EXPRESSION AND SYMPTOMS
OF ANXIETY AND DEPRESSION: THE ROLES OF CONTEXT SENSITIVITY AND FEEDBACK
SENSITIVITY.
AB - Expressive flexibility (EF), the ability to enhance and suppress emotional
expressions, predicts decreases in anxiety and depression symptoms years later
(Bonanno, Papa, Lalande, Westphal, & Coifman, 2004). Bonanno and Burton (2013)
proposed that knowing the most appropriate strategy for a situation (context
sensitivity; CS), and awareness of how well strategies are working (feedback
sensitivity; FS), partially explain this effect. We conducted a conditional
process analysis to test this theory. One hundred thirty-eight undergraduates
completed a behavioral measure of EF and self-reported symptoms of anxiety and
depression, CS, and FS over one month. CS moderated the effect of EF on one-month
changes in symptoms of anxiety and depression (p = .03): EF only predicted
decreased anxiety and depression symptoms among people low in CS. FS mediated the
effect of EF (95% CI: -.10, -.01) on changes in anxiety and depression symptoms:
higher baseline EF was associated with higher two-week FS, which predicted
decreased one-month anxiety and depression symptoms. Results suggest EF and CS
may be compensatory skills and FS may be necessary to experience the adaptive
effects of emotion regulation flexibility.
PMID- 28490834
TI - Human fatigue and the crash of the airship Italia.
AB - The airship Italia, commanded by General Umberto Nobile, crashed during its
return flight from the North Pole in 1928. The cause of the accident was never
satisfactorily explained. We present evidence that the crash may have been
fatigue-related. Nobile's memoirs indicate that at the time of the crash he had
been awake for at least 72 h. Sleep deprivation impairs multiple aspects of
cognitive functioning necessary for exploration missions. Just prior to the
crash, Nobile made three command errors, all of which are of types associated
with inadequate sleep. First, he ordered a release of lift gas when he should
have restarted engines (an example of incorrect data synthesis, with
deterioration of divergent thinking); second, he inappropriately ordered the ship
above the cloud layer (a deficiency in the assessment of relative risks); and
third, he remained above the cloud layer for a prolonged period of time (examples
of attention to secondary problems, and calculation problems). We argue that as a
result of these three errors, which would not be expected from such an
experienced commander, there was no longer enough static lift to maintain level
flight when the ship went below the cloud layer. Applying Circadian Performance
Simulation Software to the sleep-wake patterns described by Nobile in his
memoirs, we found that the predicted performance for someone awake as long as he
had been is extremely low. This supports the historical evidence that human
fatigue contributed to the crash of the Italia.
PMID- 28490835
TI - From non-preemptive to preemptive scheduling using synchronization synthesis.
AB - We present a computer-aided programming approach to concurrency. The approach
allows programmers to program assuming a friendly, non-preemptive scheduler, and
our synthesis procedure inserts synchronization to ensure that the final program
works even with a preemptive scheduler. The correctness specification is
implicit, inferred from the non-preemptive behavior. Let us consider sequences of
calls that the program makes to an external interface. The specification requires
that any such sequence produced under a preemptive scheduler should be included
in the set of sequences produced under a non-preemptive scheduler. We guarantee
that our synthesis does not introduce deadlocks and that the synchronization
inserted is optimal w.r.t. a given objective function. The solution is based on a
finitary abstraction, an algorithm for bounded language inclusion modulo an
independence relation, and generation of a set of global constraints over
synchronization placements. Each model of the global constraints set corresponds
to a correctness-ensuring synchronization placement. The placement that is
optimal w.r.t. the given objective function is chosen as the synchronization
solution. We apply the approach to device-driver programming, where the driver
threads call the software interface of the device and the API provided by the
operating system. Our experiments demonstrate that our synthesis method is
precise and efficient. The implicit specification helped us find one concurrency
bug previously missed when model-checking using an explicit, user-provided
specification. We implemented objective functions for coarse-grained and fine
grained locking and observed that different synchronization placements are
produced for our experiments, favoring a minimal number of synchronization
operations or maximum concurrency, respectively.
PMID- 28490836
TI - Prior Knowledge of Target Direction and Intended Movement Selection Improves
Indirect Reaching Movement Decoding.
AB - Objective. Previous studies have demonstrated that target direction information
presented by the dorsal premotor cortex (PMd) during movement planning could be
incorporated into neural decoder for achieving better decoding performance. It is
still unknown whether the neural decoder combined with only target direction
could work in more complex tasks where obstacles impeded direct reaching paths.
Methods. In this study, spike activities were collected from the PMd of two
monkeys when performing a delayed obstacle-avoidance task. We examined how target
direction and intended movement selection were encoded in neuron population
activities of the PMd during movement planning. The decoding performances of
movement trajectory were compared for three neural decoders with no prior
knowledge, or only target direction, or both target direction and intended
movement selection integrated into a mixture of trajectory model (MTM). Results.
We found that not only target direction but also intended movement selection was
presented in neural activities of the PMd during movement planning. It was
further confirmed by quantitative analysis. Combined with prior knowledge, the
trajectory decoder achieved the best performance among three decoders.
Conclusion. Recruiting prior knowledge about target direction and intended
movement selection extracted from the PMd could enhance the decoding performance
of hand trajectory in indirect reaching movement.
PMID- 28490837
TI - Transcriptional Profiling at High Temporal Resolution Reveals Robust
Immune/Inflammatory Responses during Rat Sciatic Nerve Recovery.
AB - After peripheral nerve injury, immune/inflammatory responses are triggered, which
are critical for nerve regeneration. Despite their importance, the underlying
molecular changes in immune/inflammatory responses remain largely unknown. In
this study, we systematically analyzed differentially expressed genes in
immune/inflammatory-related pathways at high temporal resolution and
experimentally validated gene expression changes with RT-PCR following sciatic
nerve crush in rats. We found that immune/inflammatory reactions not only occur
in the acute injury but also remained activated over two weeks after injury.
Detailed bioinformatic studies suggested that multiple immune/inflammatory
pathways, including agranulocyte adhesion and diapedesis, granulocyte adhesion
and diapedesis, IL-6 signaling, and IL-10 signaling, were sustained activated
during nerve degeneration and regeneration. Our current study expands our
understanding of the molecular basis of altered immune/inflammatory-related
pathways following injury and thus might offer the possibility of targeting
related molecules as therapeutic intervention for peripheral nerve regeneration.
PMID- 28490839
TI - Higher-Order Chromatin Regulation of Inflammatory Gene Expression.
AB - Whether it is caused by viruses and bacteria infection, or low-grade chronic
inflammation of atherosclerosis and cellular senescence, the transcription factor
(TF) NF-kappaB plays a central role in the inducible expression of inflammatory
genes. Accumulated evidence has indicated that the chromatin environment is the
main determinant of TF binding in gene expression regulation, including the
stimulus-responsive NF-kappaB. Dynamic changes in intra- and interchromosomes are
the key regulatory mechanisms promoting the binding of TFs. When an inflammatory
process is triggered, NF-kappaB binds to enhancers or superenhancers, triggering
the transcription of enhancer RNA (eRNA), driving the chromatin of the NF-kappaB
binding gene locus to construct transcriptional factories, and forming intra- or
interchromosomal contacts. These processes reveal a mechanism in which
intrachromosomal contacts appear to be cis-control enhancer-promoter
communications, whereas interchromosomal regulatory elements construct trans-form
relationships with genes on other chromosomes. This article will review emerging
evidence on the genome organization hierarchy underlying the inflammatory
response.
PMID- 28490841
TI - Unraveling Sugar Chain Signatures of the "Seeds" of Tumor Metastasis.
PMID- 28490840
TI - Toll-Like Receptor 9 Promotes Survival in SERCA2a KO Heart Failure Mice.
AB - Aim. Inflammation is important in heart failure (HF). The role of the immune
receptor toll-like receptor 9 (TLR9) in HF is not understood and not investigated
in diastolic HF. We investigated the role of TLR9 in a murine diastolic HF model
caused by cardiomyocyte SERCA2a excision. Methods and Results. We crossed SERCA2a
KO and TLR9 KO mice to generate four mouse lines. Tamoxifen-induced cardiomyocyte
SERCA2a gene excision was carried out in mice, causing diastolic HF. After 7.6
weeks, cardiac functions and dimensions were analyzed by echocardiography and
heart tissues were processed. HF mice depleted of TLR9 demonstrated reduced
survival compared to SERC2a KO mice, with a median life expectancy of 58 days
compared to 63 days. Both HF groups displayed increased left atrium size, lung
weight, fetal gene expressions, monocyte/macrophage infiltration, and fibrosis.
However, there were no significant differences between the groups. Conclusion. In
mice with SERCA2a KO-induced diastolic HF, the absence of TLR9 reduced median
life expectancy. The cause remains elusive, as all investigated HF parameters
were unaltered. Still, these findings support a salutary role of TLR9 in some
subsets of HF conditions and underline the importance for future studies on the
mechanisms of TLR9 in diastolic HF.
PMID- 28490838
TI - Adipokine Contribution to the Pathogenesis of Osteoarthritis.
AB - Recent studies have shown that overweight and obesity play an important role in
the development of osteoarthritis (OA). However, joint overload is not the only
risk factor in this disease. For instance, the presence of OA in non-weight
bearing joints such as the hand suggests that metabolic factors may also
contribute to its pathogenesis. Recently, white adipose tissue (WAT) has been
recognized not only as an energy reservoir but also as an important secretory
organ of adipokines. In this regard, adipokines have been closely associated with
obesity and also play an important role in bone and cartilage homeostasis.
Furthermore, drugs such as rosuvastatin or rosiglitazone have demonstrated
chondroprotective and anti-inflammatory effects in cartilage explants from
patients with OA. Thus, it seems that adipokines are important factors linking
obesity, adiposity, and inflammation in OA. In this review, we are focused on
establishing the physiological mechanisms of adipokines on cartilage homeostasis
and evaluating their role in the pathophysiology of OA based on evidence derived
from experimental research as well as from clinical-epidemiological studies.
PMID- 28490842
TI - The need for virtual reality simulators in dental education: A review.
AB - Virtual reality simulators are becoming an essential part of modern education.
The benefits of Virtual reality in dentistry is constantly being assessed as a
method or an adjunct to improve fine motor skills, hand-eye coordination in pre
clinical settings and overcome the monetary and intellectual challenges involved
with such training. This article, while providing an overview of the virtual
reality dental simulators, also looks at the link between virtual reality
simulation and current pedagogical knowledge.
PMID- 28490844
TI - Attitudes of dental professional staff and auxiliaries in Riyadh, Saudi Arabia,
toward disclosure of medical errors.
AB - AIM: To collect empirical data on the attitudes of dental professionals and
dental auxiliaries in Riyadh, Saudi Arabia, regarding the disclosure of medical
errors. METHODS: A cross-sectional study was conducted, involving the
administration of a questionnaire to a sample of 586 participants recruited from
over 10 government and private dental institutions in Riyadh between August 2015
and January 2016. The questionnaire collected information regarding participant
opinions on (a) personal beliefs, norms, and practices regarding medical errors,
(b) the nature of errors that should be disclosed, and (c) who should disclose
errors. RESULTS: Most (94.4%) participants preferred that medical errors should
be disclosed. However, personal preferences, perceptions of the norm and current
practices with respect to which type (seriousness) of error should be disclosed
were inconsistent. Only 17.9% of participants perceived that it was the current
practice to disclose errors resulting in "Major harm". Over 68% of respondents
reported a personal belief, a perception of the norm and a perception of current
practice that errors should be disclosed by the erring dentist. Participants at
government institutions were more likely to disclose errors than those at private
institutions. There were also significant differences in the responses with
respect to gender, age, and nationality. The implications for the development of
guidelines to help Saudi dentists adopt ethical courses of action for the
disclosure of errors are considered. CONCLUSIONS: (1) The majority of
participants personally believed that errors should be disclosed, (2) there was
little agreement between participant personal beliefs and perceptions of the norm
and practice with respect to which type of errors should be disclosed, (3) there
was strong agreement that the erring dentist is responsible for reporting errors,
and (4) the attitudes of the participants varied with respect to type of
institution, age, gender, and nationality.
PMID- 28490843
TI - Factors affecting polymerization of resin-based composites: A literature review.
AB - AIM: The aim of this review was to help clinicians improve their understanding of
the polymerization process for resin-based composites (RBC), the effects of
different factors on the process and the way in which, when controlled, the
process leads to adequately cured RBC restorations. METHODS: Ten factors and
their possible effects on RBC polymerization are reviewed and discussed, with
some recommendations to improve that process. These factors include RBC shades,
their light curing duration, increment thickness, light unit system used, cavity
diameter, cavity location, light curing tip distance from the curing RBC surface,
substrate through which the light is cured, filler type, and resin/oral cavity
temperature. CONCLUSION: The results of the review will guide clinicians toward
the best means of providing their patients with successfully cured RBC
restorations.
PMID- 28490845
TI - A survey of pediatric dentists' caries-related treatment decisions and
restorative modalities - A web-based survey.
AB - OBJECTIVE: To identify current practices and the preferred caries-related
treatment decisions and restorative modalities of primary teeth among pediatric
dental practitioners in Saudi Arabia. MATERIALS AND METHODS: This was a web-based
cross-sectional survey conducted among licensed pediatric dental practitioners in
Saudi Arabia. Following the retrieval of the email addresses from the Saudi
Dental Council, an email explaining the purpose of the study and a link to
SurveyMonkey electronic survey consisting of 23 questions was sent to all the
members registered under the pediatric dentistry practitioners, starting in
September till December 2013. The data obtained was analyzed using descriptive
statistics and chi square with and without tabulation processes. The level of
significance was set at p < 0.05. RESULTS: A total of 108 [54 (50%) male and 54
(50%) female] pediatric dental practitioners responded to the survey out of 308
targeted individuals for an overall response rate of 35.1%. About 65% of the
respondents reported that they have never considered pre-veneered or Zirconia
crowns as a restorative option for carious vital anterior primary teeth. About
40% reported doing pulpectomy and restored with composite strip crowns at all
times. About 86% of the respondents reported doing pulpotomy and stainless steel
crown for restoring carious vital posterior primary teeth whereas 73.8% reported
restoring with composite resin. However, 83.1% of the respondents reported that
they never used pre-veneered or Zirconia crowns after pulpotomy for restoring
carious vital posterior primary teeth. A significantly higher number of male
participants reported that they used esthetic pediatric crowns in their practice
compared to female participants (p < 0.001). CONCLUSION: The prevalence of use of
composite resin to restore primary teeth was higher compared to glass ionomer
cements and amalgam whereas a limited use of esthetic pediatric crowns was found
among the sample surveyed. Esthetic pediatric crowns were more utilized by male
compared to female participants.
PMID- 28490846
TI - Reliability of intra-oral camera using teledentistry in screening of oral
diseases - Pilot study.
AB - OBJECTIVE: Reliability of intra-oral camera using teledentistry in screening of
oral diseases. METHODOLOGY: A trained and calibrated examiner used intra-oral
camera to capture videos of oral cavity along with clinical examination to
evaluate caries, plaque, calculus, tooth wear and fluorosis, stains in children.
RESULTS: The mean DT and DMFT were significantly higher with use of intra-oral
camera than with clinical examination (p = 0.001 and 0.001) respectively. A
positive strong significant correlation was seen between intra-oral camera and
clinical examination with respect to DT, MT, FT and DMFT (r = 0.721, p < 0.001; r
= 0.908, p < 0.001; r = 0.869, p < 0.001; r = 0.876, p < 0.001) respectively.
Reliability of intra-oral camera when compared with clinical examination varied
from substantial to almost perfect agreement various oral conditions. Disclosed
immature plaque was not clear while mature plaque was clearly demonstrated.
CONCLUSION/RECOMMENDATIONS: Intra-oral camera was shown to be a reliable tool to
identify common oral diseases. Further studies involving applications like
sealant retention, pre-malignant lesions, recurrent apthae, gingival recession
and dental malocclusion and effectiveness in regular screening are needed.
PMID- 28490847
TI - Sexual dimorphism, pattern of third molar and mandibular second premolar agenesis
in Indian paediatric orthodontic patients.
AB - OBJECTIVE: To determine and compare the prevalence and pattern of agenesis of
third molar and mandibular second premolar in paediatric orthodontic patients of
age group 9-15 for sexual dimorphism. METHODS: The digital orthopantograph was
obtained from the archive record of patients of age group 9-15 year. Radiographs
of 301 patients were evaluated after taking exclusion criteria into account and
were assessed for the presence/absence of third molars and mandibular second
premolar. Tooth development evaluation followed the method of Demirjian et al.,
based on eight stages of tooth formation. The agenesis of third molar in maxilla
and mandible between age groups and gender was compared using Chi-squared test.
RESULTS: The rate of agenesis of third molars was observed 36.8% in the present
study. Twenty-four (24.3%) percentage of the study population showed agenesis of
all the four third molars. The agenesis of third molars was found to be higher
among males than females (p > 0.05). Prevalence of agenesis of mandibular second
premolar was 4.7-5%. CONCLUSIONS: Agenesis of third molars was more commonly seen
in the maxilla, having male predilection. Maxillary right third molar was the
most commonly missing tooth irrespective of gender.
PMID- 28490848
TI - Precise large deviations of aggregate claims in a size-dependent renewal risk
model with stopping time claim-number process.
AB - In this paper, we consider a size-dependent renewal risk model with stopping time
claim-number process. In this model, we do not make any assumption on the
dependence structure of claim sizes and inter-arrival times. We study large
deviations of the aggregate amount of claims. For the subexponential heavy-tailed
case, we obtain a precise large-deviation formula; our method substantially
relies on a martingale for the structure of our models.
PMID- 28490849
TI - A Hilbert-type fractal integral inequality and its applications.
AB - By using thefractal theory and the methods of weight function, a Hilbert-type
fractal integral inequality and its equivalent form are given. Their constant
factors are proved being the best possible, and their applications are discussed
briefly.
PMID- 28490850
TI - A new Z-eigenvalue localization set for tensors.
AB - A new Z-eigenvalue localization set for tensors is given and proved to be tighter
than those in the work of Wang et al. (Discrete Contin. Dyn. Syst., Ser. B
22(1):187-198, 2017). Based on this set, a sharper upper bound for the Z-spectral
radius of weakly symmetric nonnegative tensors is obtained. Finally, numerical
examples are given to verify the theoretical results.
PMID- 28490851
TI - New applications of the existence of solutions for equilibrium equations with
Neumann type boundary condition.
AB - Using the existence of solutions for equilibrium equations with a Neumann type
boundary condition as developed by Shi and Liao (J. Inequal. Appl. 2015:363,
2015), we obtain the Riesz integral representation for continuous linear maps
associated with additive set-valued maps with values in the set of all closed
bounded convex non-empty subsets of any Banach space, which are generalizations
of integral representations for harmonic functions proved by Leng, Xu and Zhao
(Comput. Math. Appl. 66:1-18, 2013). We also deduce the Riesz integral
representation for set-valued maps, for the vector-valued maps of Diestel-Uhl and
for the scalar-valued maps of Dunford-Schwartz.
PMID- 28490852
TI - Where Are the Beds? Housing Locations for Transition Age Youth Exiting Public
Systems.
AB - Transition age youth (TAY) from the child welfare and juvenile justice systems
experience high rates of homelessness, but little is known about the
neighborhoods to which they return after they exit these systems. This
exploratory study investigates whether housing options are located in areas where
TAY exit public systems and if the characteristics of areas surrounding these
facilities support their transition to adulthood. Results show that housing is
not related to areas where TAY exit public systems. Further, supportive housing
and shelter density is related to low-income areas. Implications for practice and
policy on housing locations for TAY are discussed.
PMID- 28490853
TI - Team Learning: New Insights Through a Temporal Lens.
AB - Team learning is a complex social phenomenon that develops and changes over time.
Hence, to promote understanding of the fine-grained dynamics of team learning,
research should account for the temporal patterns of team learning behavior.
Taking important steps in this direction, this special issue offers novel
insights into the dynamics of team learning by advocating a temporal perspective.
Based on a symposium presented at the 2016 Interdisciplinary Network for Group
Research (INGRoup) Conference in Helsinki, the four empirical articles in this
special issue showcase four different and innovative approaches to implementing a
temporal perspective in team learning research. Specifically, the contributions
highlight team learning dynamics in student teams, self-managing teams, teacher
teams, and command and control teams. The articles cover a broad range of methods
and designs, including both qualitative and quantitative methodologies, and
longitudinal as well as micro-temporal approaches. The contributors represent
four countries and five different disciplines in group research.
PMID- 28490854
TI - Effects of Sequences of Cognitions on Group Performance Over Time.
AB - Extending past research showing that sequences of low cognitions (low-level
processing of information) and high cognitions (high-level processing of
information through questions and elaborations) influence the likelihoods of
subsequent high and low cognitions, this study examines whether sequences of
cognitions are related to group performance over time; 54 primary school students
(18 triads) discussed and wrote an essay about living in another country (32,375
turns of talk). Content analysis and statistical discourse analysis showed that
within each lesson, groups with more low cognitions or more sequences of low
cognition followed by high cognition added more essay words. Groups with more
high cognitions, sequences of low cognition followed by low cognition, or
sequences of high cognition followed by an action followed by low cognition,
showed different words and sequences, suggestive of new ideas. The links between
cognition sequences and group performance over time can inform facilitation and
assessment of student discussions.
PMID- 28490855
TI - Using Transactivity to Understand Emergence of Team Learning.
AB - Team learning is a recurrent topic in research on effective teamwork. However,
research about the fact that team learning processes emerge from conversations
and the different forms this emergence can take is limited. The aim of this study
is to determine whether the extent to which team members act on each other's
reasoning (transactivity) can be used to understand how team learning processes
emerge. Research on teacher teams was used as the case study: Video recordings of
three different teacher teams were used as primary data, and the data were
analyzed using qualitative interaction analysis. The analysis shows that the
content of team learning processes changes when team members act more closely on
each other's reasoning. In particular, team learning processes related to the
storage and retrieval of information took place only in sequences in which team
members acted closely on each other's reasoning.
PMID- 28490856
TI - Team Leader Structuring for Team Effectiveness and Team Learning in Command-and
Control Teams.
AB - Due to their crucial and highly consequential task, it is of utmost importance to
understand the levers leading to effectiveness of multidisciplinary emergency
management command-and-control (EMCC) teams. We argue that the formal EMCC team
leader needs to initiate structure in the team meetings to support organizing the
work as well as facilitate team learning, especially the team learning process of
constructive conflict. In a sample of 17 EMCC teams performing a realistic EMCC
exercise, including one or two team meetings (28 in sum), we coded the team
leader's verbal structuring behaviors (1,704 events), rated constructive conflict
by external experts, and rated team effectiveness by field experts. Results show
that leaders of effective teams use structuring behaviors more often (except
asking procedural questions) but decreasingly over time. They support
constructive conflict by clarifying and by making summaries that conclude in a
command or decision in a decreasing frequency over time.
PMID- 28490857
TI - Effects of the Caregiver Interaction Profile Training on Caregiver-Child
Interactions in Dutch Child Care Centers: A Randomized Controlled Trial.
AB - BACKGROUND: Previous studies underscore the need to improve caregiver-child
interactions in early child care centers. OBJECTIVE: In this study we used a
randomized controlled trial to examine whether a 5-week video feedback training
can improve six key interactive skills of caregivers in early child care centers:
Sensitive responsiveness, respect for autonomy, structuring and limit setting,
verbal communication, developmental stimulation, and fostering positive peer
interactions. METHOD: A total of 139 caregivers from 68 early child care groups
for 0- to 4-year-old children in Dutch child care centers participated in this
RCT, 69 in the intervention condition and 70 in the control condition. Caregiver
interactive skills during everyday interactions with the children were rated from
videotape using the Caregiver Interaction Profile (CIP) scales at pretest,
posttest, and follow-up 3 months after the posttest. RESULTS: Results at posttest
indicate a significant positive training effect on all six caregiver interactive
skills. Effect sizes of the CIP training range between d = 0.35 and d = 0.79.
Three months after the posttest, caregivers in the intervention group still
scored significantly higher on sensitive responsiveness, respect for autonomy,
verbal communication, and fostering positive peer interactions than caregivers in
the control group with effect sizes ranging between d = 0.47 and d = 0.70.
CONCLUSIONS: This study shows that the quality of caregiver-child interactions
can be improved for all six important caregiver skills, with a relatively short
training program. Possible ways to further improve the training and to implement
it in practice and education are discussed.
PMID- 28490858
TI - Social Network Size and Cognitive Functioning in Middle-Aged Adults: Cross
Sectional and Longitudinal Associations.
AB - The objective of the present study was to examine relations between social
network size and three cognitive abilities (episodic memory, semantic memory,
visuospatial ability) in middle-aged adults. We analyzed cross-sectional data on
social network size and cognitive functioning that were available for 804
participants aged 40-60 years. In addition, we examined 5- and 10-year follow-up
measurements of cognitive functioning that were available for 604 and 255
participants, respectively. Cross-sectional analyses revealed a positive
association between social network size and each of the three cognitive
abilities. Baseline network size was positively related to 5-year changes in
semantic memory, and to 10-year changes in semantic as well as episodic memory,
but was unrelated to changes in visuospatial performance. A minor portion of the
sample (n = 131) had 10-year follow-up data on network size. Cross-lagged panel
correlations revealed that baseline network size was associated with follow-up
measurement in cognitive functioning (episodic memory, semantic memory), whereas
baseline cognitive performance was unrelated to future network size. Together,
the results demonstrate a small but positive relation between network size and
declarative memory abilities, in line with models proposing a cognitive reserve
built up by factors such as the increased cognitive stimulation associated with a
more extensive social network.
PMID- 28490859
TI - Blood is Thicker Than Water: Geography and the Dispersal of Family
Characteristics Across the Globe.
AB - This article introduces a new dataset of historical family characteristics based
on ethnographic literature. The novelty of the dataset lies in the fact that it
is constructed at the level of the ethnic group. To test the possibilities of the
dataset, we construct a measure of family constraints on women's agency from it
and explore its correlation to a number of geographical factors.
PMID- 28490860
TI - Choroidal structure determined by binarizing optical coherence tomography images
in eyes with reticular pseudodrusen.
AB - PURPOSE: To compare the choroidal structure beneath the macular area in eyes with
reticular pseudodrusen (RPD) and age-matched controls. METHODS: This study was
performed at Nara Medical University Hospital, Japan. Twenty eyes of 14 patients
(82.3+/-4.2 years, mean +/- standard deviation) with RPD and 35 eyes of 20 age
matched controls (81.5+/-6.0 years) were studied. The choroidal structure was
determined by binarizing the images obtained by enhanced depth imaging optical
coherence tomography in all patients and controls. The total, luminal, and
stromal choroidal areas were quantified by the binarization method. RESULTS: The
total choroidal area of the eyes with RPD was significantly smaller than that of
control eyes (P=0.001, unpaired t-test). Both the luminal and stromal areas in
eyes with RPD were significantly smaller than that of control eyes (P=0.001,
paired t-test), but there was no significant difference in the luminal/stromal
ratio between eyes with RPD and control eyes. CONCLUSION: The total, luminal, and
stromal choroidal areas in eyes with RPD were smaller than those of the control
eyes. The reduction of the choroidal luminal and stromal areas may be due to a
loss of the oxygen demand of the choroid due to RPE dysfunction.
PMID- 28490861
TI - Efficacy of intravitreal aflibercept injections for Japanese patients with
polypoidal choroidal vasculopathy.
AB - PURPOSE: To evaluate the efficacy of intravitreal aflibercept therapy in
treatment-naive Japanese patients with polypoidal choroidal vasculopathy (PCV)
using Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores. SUBJECTS
AND METHODS: This study was a prospective, nonrandomized, interventional
exploratory clinical trial performed in an institutional setting. Patients with
PCV were treated with intravitreal aflibercept 2 mg/0.05 mL every 2 months after
3 initial monthly doses, for 1 year. Visual acuity test using the ETDRS chart and
indocyanine green angiography was performed at baseline and at 6 and 12 months
after initiating the treatment, in addition to routine examinations performed at
each visit. The main outcome measure was the proportion of patients who achieved
<15 ETDRS letter score loss. RESULTS: Twenty-two patients were enrolled in this
study. Nineteen (86%) patients were eligible for analysis. All the patients
maintained their visual acuity (<15 ETDRS letter score loss) at 12 months. The
ETDRS letter scores were 64.1 at baseline and 69.8 at 12 months (P<0.039). The
polyps regressed completely in 14 (74%) patients at 12 months. Cataract
progressed in 1 eye, but this progression was considered to be a senile change.
CONCLUSIONS: Japanese patients with treatment-naive PCV, who were treated with
intravitreal aflibercept every 2 months after 3 initial monthly doses, exhibited
a significant increase in ETDRS letter scores and a high rate of polyp resolution
at 12 months.
PMID- 28490862
TI - Ultra-wide-field fluorescein angiography in diabetic retinopathy: a narrative
review.
AB - Fluorescein angiography (FA) is a useful examination in patients suffering from
diabetic retinopathy (DR). Traditional angiograms explore 30 degrees -50 degrees
of the retina at once; however, visualization of peripheral retina is fundamental
in order to assess nonperfused areas, vascular leakage, microvascular
abnormalities, and neovascularizations. In order to expand the field of view,
wide-field and ultra-wide-field imaging has been developed allowing to image up
to 200 degrees of retinal surface in one single shot. The aim of this narrative
review was to provide an overview of the role of the most recent technique of
ultra-wide-field fluorescein angiography in DR.
PMID- 28490864
TI - Adherence to tobramycin inhaled powder vs inhaled solution in patients with
cystic fibrosis: analysis of US insurance claims data.
AB - PURPOSE: Tobramycin inhalation powder (TIP), the first dry-powder inhaled
antibiotic for pulmonary Pseudomonas aeruginosa infection, is associated with
reduced treatment burden, increased patient satisfaction, and higher self
reported adherence for cystic fibrosis (CF) patients. We compared adherence in CF
patients newly treated with TIP with those newly treated with the traditional
tobramycin inhalation solution (TIS), using US insurance claims data. PATIENTS
AND METHODS: From the Truven MarketScan(r) database, we identified CF patients
chronically infected with P. aeruginosa who had been prescribed TIP between May
1, 2013 to December 31, 2014, or TIS between September 1, 2010 to April 30, 2012
with at least 12 months of continuous medical and pharmacy benefits prior to and
following prescription. TIP and TIS adherence levels were assessed. RESULTS: A
total of 145 eligible patients were identified for the TIP cohort and 306 for the
TIS cohort. Significant differences in age distribution (25.0 vs 21.9 years for
TIP vs TIS, respectively, P=0.017), type of health plan (P=0.014), employment
status (72.4% vs 63.4% of TIP vs TIS patients in full-time employment, P=0.008),
and some comorbidities were observed between the two cohorts. Although a
univariate analysis found no significant differences between TIP and TIS (odds
ratio [OR] 1.411, 95% confidence interval [CI] 0.949-2.098), TIP was moderately
associated with higher adherence levels compared with TIS in a multivariable
analysis, once various demographic and clinical characteristics were adjusted
for. These included geographic location (OR: 1.566, CI: 1.016-2.413) and certain
comorbidities. CONCLUSION: This study of US patient data supports previous
findings that TIP is associated with better adherence compared with TIS; however,
further studies will be required to fully elucidate differences in adherence
between TIP and TIS.
PMID- 28490863
TI - Development and evaluation of a new modular nanotransporter for drug delivery
into nuclei of pathological cells expressing folate receptors.
AB - PURPOSE: Modular nanotransporters (MNTs) are artificial multifunctional systems
designed to facilitate receptor-specific transport from the cell surface into the
cell nucleus through inclusion of polypeptide domains for accomplishing receptor
binding and internalization, as well as sequential endosomal escape and nuclear
translocation. The objective of this study was to develop a new MNT targeted at
folate receptors (FRs) for precise delivery of therapeutic cargo to the nuclei of
FR-positive cells and to evaluate its potential, particularly for delivery of
therapeutic agents (eg, the Auger electron emitter 111In) into the nuclei of
target cancer cells. METHODS: A FR-targeted MNT was developed by site-specific
derivatization of ligand-free MNT with maleimide-polyethylene glycol-folic acid.
The ability of FR-targeted MNT to accumulate in target FR-expressing cells was
evaluated using flow cytometry, and intracellular localization of this MNT was
assessed using confocal laser scanning microscopy of cells. The cytotoxicity of
the 111In-labeled FR-targeted MNT was evaluated on HeLa and U87MG cancer cell
lines expressing FR. In vivo micro-single-photon emission computed tomography/CT
imaging and antitumor efficacy studies were performed with intratumoral injection
of 111In-labeled FR-targeted MNT in HeLa xenograft-bearing mice. RESULTS: The
resulting FR-targeted MNT accumulated in FR-positive HeLa cancer cell lines
specifically and demonstrated the ability to reach its target destination - the
cell nuclei. 111In-labeled FR-targeted MNT demonstrated efficient and specific FR
positive cancer cell eradication. A HeLa xenograft in vivo model revealed
prolonged retention of 111In delivered by FR-targeted MNT and significant tumor
growth delay (up to 80% growth inhibition). CONCLUSION: The FR-targeted MNT met
expectations of its ability to deliver active cargo into the nuclei of target FR
positive cells efficiently and specifically. As a result of this finding the new
FR-targeted MNT approach warrants broad evaluation.
PMID- 28490865
TI - Poor 1st-year adherence to anti-osteoporotic therapy increases the risk of
mortality in patients with magnetic resonance imaging-proven acute osteoporotic
vertebral fractures.
AB - AIM: Anti-osteoporotic therapy requires years of proper compliance to reduce the
risk of fractures. This study investigated the effects of 1st-year adherence to
anti-osteoporotic treatment on the risk of mortality in patients with magnetic
resonance imaging-proven acute osteoporotic vertebral fractures after
vertebroplasty. PATIENTS AND METHODS: This retrospective study included 294
patients (252 females; mean age, 73.93+/-7.18 years) with osteoporosis and acute
vertebral fractures treated with vertebroplasty between January 2001 and December
2007. Sex, age, body mass index, comorbidities, previous hip fracture, number of
vertebral fractures, 5-year re-fracture rate, and use of anti-osteoporotic
therapy were recorded for each patient. Adherence was determined according to
compliance and persistence for 1 year. Compliance was calculated as the
medication possession ratio (MPR), and persistence as the time from treatment
initiation to discontinuation. Poor adherence was defined as either non
compliance or non-persistence. RESULTS: The MPR of the patients at 1 year was
55.1%, with a persistence rate of 69.4% and a poor adherence rate of 62.6%. Cox
regression analysis revealed that poor adherence to medications was associated
with a significantly higher risk of mortality after adjustment for potential
confounders (hazard ratio [HR]: 1.75; 95% CI: 1.13-2.71). Poor adherence to
medications was significantly associated with an increase in the rate of
infection (HR: 4.56; 95% CI: 1.12-18.52), which was the most common cause of
death. CONCLUSION: Poor adherence to anti-osteoporotic therapy significantly
increases the risk of morality, possibly due to an increased risk of infection.
Efforts should be made to improve adherence.
PMID- 28490866
TI - Nonpharmacological interventions to treat physical frailty and sarcopenia in
older patients: a systematic overview - the SENATOR Project ONTOP Series.
AB - BACKGROUND: Physical frailty (PF) and sarcopenia are predictors of negative
health outcomes such as falls, disability, hospitalization, and death. Some
systematic reviews (SRs) have been published on different nonpharmacological
treatments of frailty and sarcopenia using heterogeneous definitions of them.
OBJECTIVE: To critically appraise the evidence from SRs of the primary studies on
nonpharmacological interventions to treat PF (defined by Fried's frailty
phenotype) and sarcopenia (defined by the EWGSOP) in older patients. DESIGN:
Overview of SRs and meta-analysis of comparative studies. DATA SOURCES: PubMed,
Cochrane Database of Systematic Reviews, EMBASE, and CINAHL were searched in
October 2015. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: SRs that included at
least one comparative study evaluating any nonpharmacological intervention to
treat PF or sarcopenia in older patients in any health care setting. Any primary
study described in these SRs with experimental design was included. DATA
EXTRACTION AND MANAGEMENT: Two reviewers independently screened titles,
abstracts, and full-texts of articles. Quality assessment was carried out by
using criteria from the Cochrane Collaboration and the GRADE working group.
RESULTS: Ten SRs with 5 primary studies satisfied the inclusion criteria. The
most frequent interventions in the included studies were physical exercise (4)
and nutritional supplementation (2). Muscle strength (MS; except for one study in
a frail population) and physical performance (PP; except for another study in a
frail population) improved with exercise and amino acid supplementation in frail
and sarcopenic old adults. Falls and activities of daily living were assessed in
two studies with opposite results. The overall quality of the evidence was low.
CONCLUSION: This overview of SRs highlights the importance of exercise
interventions with or without nutritional supplementation to improve the PP in
community-dwelling patients aged >65 years with PF and sarcopenia. MS improved
with multidisciplinary treatment and exercise interventions in this population.
PMID- 28490867
TI - Promoting the inclusion of vital-capacity data in the bronchodilator response.
PMID- 28490868
TI - Serum IL-1beta and IL-17 levels in patients with COPD: associations with clinical
parameters.
AB - COPD is a chronic airway inflammatory disease characterized mainly by neutrophil
airway infiltrations. Interleukin (IL)-1beta and IL-17 are the key mediators of
neutrophilic airway inflammation in COPD. This study was undertaken to evaluate
the serum IL-1beta and IL-17 levels and associations between these two key
mediators with clinical parameters in COPD patients. Serum samples were collected
from 60 COPD subjects during the acute exacerbation of COPD, 60 subjects with
stable COPD and 40 healthy control subjects. Commercial enzyme-linked
immunosorbent assay kits were used to measure the serum IL-1beta and IL-17
concentrations. The association between serum IL-1beta and IL-17 with FEV1%
predicted, C-reactive protein, neutrophil percentage and smoking status (pack
years) was assessed in the COPD patients. We found that serum IL-1beta and IL-17
levels in acute exacerbation of COPD subjects were significantly higher than that
in stable COPD or control subjects and were positively correlated to serum C
reactive protein levels, neutrophil % and smoking status (pack-years) but
negatively correlated with FEV1% predicted in COPD patients. More importantly,
serum IL-1beta levels were markedly positively associated with serum IL-17 levels
in patients with COPD (P=0.741, P<0.001). In conclusion, elevated serum IL-1beta
and IL-17 levels may be used as a biomarker for indicating persistent
neutrophilic airway inflammation and potential ongoing exacerbation of COPD.
PMID- 28490869
TI - Pulmonary infection control window as a switching point for sequential
ventilation in the treatment of COPD patients: a meta-analysis.
AB - PURPOSE: Choosing the appropriate time to switch to noninvasive positive-pressure
ventilation (NPPV) plays a crucial role in promoting successful weaning. However,
optimal timing for transitioning and weaning patients from mechanical ventilation
(MV) to NPPV has not been clearly established. In China, the pulmonary infection
control (PIC) window as a switching point for weaning from MV has been performed
for many years, without definitive evidence of clinical benefit. This study aimed
to summarize the evidence for NPPV at the PIC window for patients with
respiratory failure from COPD. METHODS: A comprehensive search for randomized
controlled trials (RCTs) was performed. The trials were all parallel studies
comparing the PIC window weaning strategy versus conventional weaning strategy in
treatment of patients with respiratory failure due to COPD. RESULTS: Sixteen
studies of 647 participants were eligible. When compared with conventional
weaning strategy, early extubation followed by NPPV at the point of PIC window
significantly reduced the mortality rate (risk ratios [RRs] 0.36, 95% confidence
interval [CI] 0.23 to 0.57) and ventilator-associated pneumonia (VAP) (RR 0.28,
95% CI 0.19 to 0.41); it also decreased the duration of invasive ventilation
(weighted mean difference [WMD] -7.68 days, 95% CI -9.43 to -5.93) and total
duration of ventilation (WMD -5.93 days, 95% CI -7.29 to -4.58), which also
shortened the lengths of stay in an intensive care unit (WMD -8.51 days, 95% CI
10.23 to -6.79), as well as length of stay in hospital (WMD -8.47 days, 95% CI
8.61 to -7.33). CONCLUSION: The results showed that the PIC window as a switching
point for sequential ventilation in treatment of respiratory failure in COPD
patients may be beneficial. It might yield not only relevant information for
caregivers in China but also new insights for considering the PIC window by
physicians in other countries.
PMID- 28490870
TI - Pre- and post-bronchodilator airway obstruction are associated with similar
clinical characteristics but different prognosis - report from a population-based
study.
AB - INTRODUCTION: According to guidelines, the diagnosis of COPD should be confirmed
by post-bronchodilator (post-BD) airway obstruction on spirometry; however, in
clinical practice, this is not always performed. The aim of this population-based
study was to compare clinical characteristics and prognosis, assessed as
mortality, between subjects with airway obstruction divided into pre- but not
post-BD obstruction, post-BD airway obstruction (COPD), and subjects without
airway obstruction. MATERIALS AND METHODS: In 2002-2004, four adult population
based cohorts were reexamined with spirometry and structured interview. Subjects
with airway obstruction, with a ratio of forced expiratory volume in 1 s to
(forced) vital capacity <0.70 (n=993), were identified together with sex- and age
matched referents (n=993). These subjects were further divided into subjects with
pre- but not post-BD airway obstruction (pre- not post-BD obstruction) and
subjects with post-BD airway obstruction (COPD). Mortality data were collected
until December 31, 2014. RESULTS: Out of 993 subjects with airway obstruction,
736 (74%) had COPD and 257 (26%) pre- not post-BD obstruction. Any respiratory
symptoms, allergic rhinitis, asthma, exacerbations, and comorbidities were
equally common among subjects with COPD and pre- not post-BD obstruction, but
less common among nonobstructive subjects. Mortality was highest among subjects
with COPD and higher in men than in women. In both sexes, COPD, but not pre- not
post-BD obstruction, was associated with an increased risk for death compared to
those without airway obstruction. When COPD was divided into Global Initiative
for Chronic Obstructive Lung Disease (GOLD) stages, GOLD 2 and 3-4 had an
increased risk for death when compared to the nonobstructive group, also when
adjusted for common confounders and comorbidities such as heart disease,
diabetes, and anxiety/depression. CONCLUSION: Even though subjects with COPD and
pre- not post-BD obstruction had fairly similar presentation of clinical
characteristics, only those with COPD, specifically GOLD stage >=2, had increased
risk for death when compared with nonobstructive subjects.
PMID- 28490871
TI - Home noninvasive positive pressure ventilation with built-in software in stable
hypercapnic COPD: a short-term prospective, multicenter, randomized, controlled
trial.
AB - BACKGROUND: The benefits of noninvasive positive pressure ventilation (NPPV) in
patients with hypercapnic COPD are controversial. It is presumed that methodology
and appropriate use of NIV ventilator might be crucial for the outcomes. With the
new built-in software, the performance of NIV can be monitored at home, which can
guarantee the compliance and appropriate use. This study investigated effects of
home use of NIV in hypercapnia in COPD patients using the NIV ventilator with
built-in software for monitoring. METHODS: The current multicenter prospective,
randomized, controlled trial enrolled patients with stable GOLD stages III and IV
hypercapnic COPD. Patients were randomly assigned via a computer-generated
randomization sequence, with a block size of four patients, to continue optimized
treatment (control group) or to receive additional NPPV (intervention group) for
3 months. The primary outcome was arterial carbon dioxide pressure (PaCO2). Data
were derived from built-in software and analyzed every 4 weeks. Analysis was
carried out with the intention to treat. This study is registered with
ClinicalTrials.gov, number NCT02499718. RESULTS: Patients were recruited from 20
respiratory units in China from October 1, 2015, and recruitment was terminated
with a record of the vital statistics on May 31, 2016. A total of 115 patients
were randomly assigned to the NPPV group (n=57) or the control group (n=58).
Patients complied well with NPPV therapy (mean [+/- standard deviation] day use
5.6+/-1.4 h). The mean estimation of leaks was 37.99+/-13.71 L/min. The changes
in PaCO2 (-10.41+/-0.97 vs -4.32+/-0.68 mmHg, P=0.03) and 6-min walk distance
(6MWD) (38.2% vs 18.2%, P=0.02) were statistically significant in the NPPV group
versus the control group. COPD assessment test (CAT) showed a positive trend
(P=0.06) in favor of the NPPV group. Pulmonary function and dyspnea were not
different between groups. CONCLUSION: Ventilators equipped with built-in software
provided methodology for monitoring NIV use at home, which could facilitate the
improvement of compliance and quality control of NIV use. It was shown that three
months use of NIV at home could reduce the PaCO2 and improve exercise tolerance
(6MWD) in chronic hypercapnic COPD patients.
PMID- 28490872
TI - Correlation between fractional exhaled nitric oxide and sputum eosinophilia in
exacerbations of COPD.
AB - INTRODUCTION: Measurements of eosinophils in induced sputum and fractional
exhaled nitric oxide (FeNO) are noninvasive biomarkers for assessing airway
inflammation phenotypes in chronic obstructive pulmonary disease (COPD).
Nevertheless, the clinical application of the correlation between FeNO levels and
sputum eosinophilia is controversial. The study aimed to investigate the
correlation and predictive relationship between FeNO levels and sputum
eosinophils in patients with COPD exacerbation. It also examined the relationship
between FeNO levels and blood eosinophil percentage. METHODS: A total of 163
patients with COPD exacerbation were included in the cross-sectional study. All
patients underwent the following on the same day: FeNO test, spirometry,
bronchodilator reversibility test, induced sputum, and routine blood test. They
were classified as eosinophilic group or noneosinophilic group based on sputum
eosinophilic percentage (>=2.5%)/FeNO levels (>=32 parts per billion [ppb]).
RESULTS: FeNO levels and blood eosinophilic percentage were higher in patients
with sputum eosinophilia (n=62) compared to those without (31.35 ppb versus 21.43
ppb, P=0.015; 2.71% versus 0.98%, P<0.0001, respectively). Sputum eosinophilic
percentage was higher with raised FeNO (n=34) compared to those with FeNO <32 ppb
(5.12% versus 3.12%, P=0.007). Eosinophils in induced sputum correlated with both
FeNO levels (rho=0.221, P=0.005) and blood eosinophilic percentage (rho=0.399,
P<0.001). There was no relationship between FeNO and blood eosinophilic
percentage. Blood eosinophilic percentage was predictive of sputum eosinophilia
(95% confidence interval [CI] =0.65-0.81, P<0.001) at a cutoff point of 0.65%
(sensitivity =73%, specificity =61.3%). FeNO levels were predictive of sputum
eosinophilia (95% CI =0.53-3,071, P=0.012) at a cutoff point of 17.5 ppb
(sensitivity =65.1%, specificity =56.4%). CONCLUSION: The clinical relevance of
this study provides evidence that inflammatory biomarkers, including sputum
eosinophilic percentage, FeNO level, and blood eosinophilic percentage, can be
used to positively diagnose eosinophilic COPD. The FeNO level and blood
eosinophilic counts/percentage, which determine an optimal cutoff for sputum
eosinophilia, need more studies.
PMID- 28490873
TI - Tailoring stimuli-responsive delivery system driven by metal-ligand coordination
bonding.
AB - In this study, a novel coordination bonding system based on metal-tannic acid
(TA) architecture on zein/carboxymethyl chitosan (CMCS) nanoparticles (NPs) was
investigated for the pH-responsive drug delivery. CMCS has been reported to coat
on zein NPs as delivery vehicles for drugs or nutrients in previous studies. The
cleavage of either the "metal-TA" or "NH2-metal" coordination bonds resulted in
significant release of guest molecules with high stimulus sensitivity, especially
in mild acidic conditions. The prepared metal-TA-coated zein/CMCS NPs (zein/CMCS
TA/metal NPs) could maintain particle size in cell culture medium at 37 degrees
C, demonstrating good stability compared with zein/CMCS NPs. In vitro release
behavior of doxorubicin hydrochloride (DOX)-loaded metal-TA film-coated zein/CMCS
NPs (DOX-zein/CMCS-TA/metal NPs) showed fine pH responsiveness tailored by the
ratio of zein to CMCS as well as the metal species and feeding concentrations.
The blank zein/CMCS-TA/metal NPs (NPs-TA/metal) were of low cytotoxicity, while a
high cytotoxic activity of DOX-zein/CMCS-TA/metal NPs (DOX-NPs-TA/metal) against
HepG2 cells was demonstrated by in vitro cell assay. Confocal laser scanning
microscopy (CLSM) and flow cytometry were combined to study the uptake efficiency
of DOX-NPs or DOX-NPs-TA/metal. This system showed significant potential as a
highly versatile and potent platform for drug delivery.
PMID- 28490874
TI - Quantitative and multiplexed detection for blood typing based on quantum dot
magnetic bead assay.
AB - BACKGROUND: Accurate and reliable blood grouping is essential for safe blood
transfusion. However, conventional methods are qualitative and use only single
antigen detection. We overcame these limitations by developing a simple,
quantitative, and multiplexed detection method for blood grouping using quantum
dots (QDs) and magnetic beads. METHODS: In the QD fluorescence assay (QFA), blood
group A and B antigens were quantified using QD labeling and magnetic beads, and
the blood groups were identified according to the R value (the value was
calculated with the fluorescence intensity from dual QD labeling) of A and B
antigens. The optimized performance of QFA was established by blood typing 791
clinical samples. RESULTS: Quantitative and multiplexed detection for blood group
antigens can be completed within 35 min with more than 105 red blood cells. When
conditions are optimized, the assay performance is satisfactory for weak samples.
The coefficients of variation between and within days were less than 10% and the
reproducibility was good. The ABO blood groups of 791 clinical samples were
identified by QFA, and the accuracy obtained was 100% compared with the tube
test. Receiver-operating characteristic curves revealed that the QFA has high
sensitivity and specificity toward clinical samples, and the cutoff points of the
R value of A and B antigens were 1.483 and 1.576, respectively. CONCLUSION: In
this study, we reported a novel quantitative and multiplexed method for the
identification of ABO blood groups and presented an effective alternative for
quantitative blood typing. This method can be used as an effective tool to
improve blood typing and further guarantee clinical transfusion safety.
PMID- 28490875
TI - Mechanism of transdermal permeation promotion of lipophilic drugs by ethosomes.
AB - Ethosomes can promote the penetration of lipophilic drugs into the skin, but the
underlying mechanism is still unknown. The purpose of this study was to
investigate the mechanism of transdermal permeation promotion of lipophilic drugs
by ethosomes. The formulation of ethosomes was optimized using the Box-Behnken
experimental design, in which Rhodamine B and 1-palmitoyl-2-{12-[(7-nitro-2-1,3
benzoxadiazol-4-yl)amino]dodecanoyl}-sn-glycero-3-phosphocholine were used to
simulate a model lipophilic drug and act as a fluorescent tracer of ethosomal
phospholipids, respectively. Liposomes with the same phospholipid concentration
and a hydroethanolic solution with the same ethanol concentration were also
prepared as controls. The percutaneous progression of the above fluorescent
preparations was observed by confocal laser scanning microscopy, and the
fluorescence intensity of the images was analyzed. The optimized ethosome
formulation consisted of 2.45% yolk phospholipids, 30% ethanol, and 67.55%
distilled water. The percutaneous permeation of Rhodamine B in the optimized
ethosomes was superior to that in hydroethanolic solution (P<0.05) and liposomes
(P<0.05). The ethosomes could penetrate the skin via the percutaneous pathway of
the hair follicle and stratum corneum, while during the process of penetration,
the vesicles were broken and the phospholipids were retained in the upper
epidermis, with the test compounds penetrating gradually. The superior
percutaneous penetration of ethosomes was linked to the synergistic effects of
their ingredients. The percutaneous pathways of ethosomes included open hair
follicles and stratum corneum pathways. In addition, the vesicles might break up
during percutaneous penetration in the superficial layer of the skin, allowing
the test compounds to keep permeating into the deeper layer alone, while the
phospholipid was retained in the upper epidermis.
PMID- 28490876
TI - One-pot synthesis of dextran-coated iron oxide nanoclusters for real-time
regional lymph node mapping.
AB - The intraoperative precision cleaning of lymph nodes (LNs) is an essential
component of treating neoplastic disease. To develop efficient probes for the
targeted detection of LNs that could act as carriers for the specific diagnosis
and treatment of metastatic LNs in the future, dextran-coated iron oxide
nanoclusters (DIONs) were synthesized using a one-pot coprecipitation procedure.
These modified DIONs have good water dispersibility, cytocompatibility, an
optimum size, and a stable, dark brown color for LN imaging. In this study,
cytotoxicity was evaluated using lymphatic endothelial cells (LECs) to predict
biosafety and biocompatibility. Most importantly, the effectiveness of DIONs in
mapping perigastric LNs in Sprague Dawley rats following injection into the
gastric submucosal layer was demonstrated. In addition, a long-term tracing in
vivo (from 4 days to 3 months) indicated that the DIONs had good biosafety and
biocompatibility according to an evaluation of the behavior and blood
biochemistry of the rat and a histopathological examination of the important
organs.
PMID- 28490877
TI - Low-density lipoprotein-coupled micelles with reduction and pH dual sensitivity
for intelligent co-delivery of paclitaxel and siRNA to breast tumor.
AB - Multidrug resistance (MDR) is a major obstacle for the clinical therapy of
malignant human cancers. The discovery of RNA interference provides efficient
gene silencing within tumor cells for reversing MDR. In this study, a new "binary
polymer" low-density lipoprotein-N-succinyl chitosan-cystamine-urocanic acid (LDL
NSC-SS-UA) with dual pH/redox sensitivity and targeting effect was synthesized
for the co-delivery of breast cancer resistance protein small interfering RNA
(siRNA) and paclitaxel (PTX). In vivo, the co-delivering micelles can accumulate
in tumor tissue via the enhanced permeability and retention effect and the
specific recognition and combination of LDL and LDL receptor, which is
overexpressed on the surface of tumor cell membranes. The siRNA-PTX-loaded
micelles inhibited gene and drug release under physiological conditions while
promoting fast release in an acid microenvironment or in the presence of
glutathione. The micelles escaped from the lysosome through the proton sponge
effect. Additionally, the micelles exhibited superior antitumor activity and
downregulated the protein and mRNA expression levels of breast cancer resistance
protein in MCF-7/Taxol cells. The biodistribution and antitumor studies proved
that the siRNA-PTX-loaded micelles possessed prolonged circulation time with a
remarkable tumor-targeting effect and effectively inhibited tumor growth.
Therefore, the novel dual pH/redox-sensitive polymers co-delivering siRNA and PTX
with excellent biocompatibility and effective reversal of MDR demonstrate a
considerable potential in cancer therapy.
PMID- 28490879
TI - Methodological assessment of the reduction of the content of impurities in
nimodipine emulsion via the use of 21 amino acid protection.
AB - PURPOSE: The present study examined the factors affecting the content of
impurities of nimodipine (NMP) emulsion and the associated methods of compound
protection. METHODS: Destructive testing of NMP emulsion and its active
pharmaceutical ingredient (API) were conducted, and ultracentrifugation was used
to study the content of impurities in two phases. The impurity of NMP was
measured under different potential of hydrogen (pH) conditions, antioxidants and
pH-adjusting agents. RESULTS: Following destruction, the degradation of NMP
notably occurred in the basic environment. The consumption of the pH-adjusting
agent NaOH was proportional to the production of impurities since the inorganic
base and/or acid promoted the degradation of NMP. The organic antioxidants,
notably amino acids with an appropriate length of intermediate chain and electron
donating side group, exhibited improved antioxidant effects compared with
inorganic antioxidants. The minimal amount of impurities was produced following
addition of 0.04% lysine and 0.06% leucine in the aqueous phase and adjustment of
the pH to a range of 7.5-8.0 in the presence of acetic acid solution. CONCLUSION:
NMP was more prone to degradation in an oxidative environment, in an aqueous
phase and/or in the presence of inorganic pH-adjusting agents and antioxidants.
The appropriate antioxidant and pH-adjusting agent should be selected according
to the chemical structure, while destructive testing of the drug is considered to
play the optimal protective effect.
PMID- 28490878
TI - A novel injectable calcium phosphate-based nanocomposite for the augmentation of
cannulated pedicle-screw fixation.
AB - Polymethyl methacrylate (PMMA)-augmented cannulated pedicle-screw fixation has
been routinely performed for the surgical treatment of lumbar degenerative
diseases. Despite its satisfactory clinical outcomes and prevalence, problems and
complications associated with high-strength, stiff, and nondegradable PMMA have
largely hindered the long-term efficacy and safety of pedicle-screw fixation in
osteoporotic patients. To meet the unmet need for better bone cement for
cannulated pedicle-screw fixation, a new injectable and biodegradable
nanocomposite that was the first of its kind was designed and developed in the
present study. The calcium phosphate-based nanocomposite (CPN) exhibited better
anti-pullout ability and similar fluidity and dispersing ability compared to
clinically used PMMA, and outperformed conventional calcium phosphate cement
(CPC) in all types of mechanical properties, injectability, and biodegradability.
In term of axial pullout strength, the CPN-augmented cannulated screw reached the
highest force of ~120 N, which was higher than that of PMMA (~100 N) and CPC (~95
N). The compressive strength of the CPN (50 MPa) was three times that of CPC, and
the injectability of the CPN reached 95%. In vivo tests on rat femur revealed
explicit biodegradation of the CPN and subsequent bone ingrowth after 8 weeks.
The promising results for the CPN clearly suggest its potential for replacing
PMMA in the application of cannulated pedicle-screw fixation and its worth of
further study and development for clinical uses.
PMID- 28490880
TI - Protective efficacy of a single salvianolic acid A treatment on photothrombosis
induced sustained spatial memory impairments.
AB - With respect to the high burden of ischemic stroke and the absence of
pharmacological treatment for promoting rehabilitation, promising candidates with
specific effects on long-term functional recovery are highly desired. Candidates
need reasonable experimental paradigms to evaluate the long-term functional
outcome focused on ischemia-induced sensorimotor and memory deficits. "Danshen",
a traditional Chinese herb, has long been used to treat coronary and cerebral
vascular diseases as well as dementia. Salvianolic acid A (SAA), one of the major
active ingredients of Danshen, was demonstrated to be effective in protecting
against cerebral ischemic injury. Here, employing an experimental stroke model
induced by photothrombosis in the unilateral frontal cortex of rats, we
investigated whether SAA has long-term protective effects on ischemia-induced
sensorimotor and memory deficits in our behavioral tests. The results indicated
that a single SAA treatment improved the cortical ischemia-induced sensorimotor
deficits during 15 days' cylinder test period, and alleviated ischemia-induced
sustained spatial memory impairments during the 2 months' dependent Morris Water
Maze (MWM) tests. In addition, either ischemic injury or SAA treatment did not
show any changes compared with sham group in other behavioral tests including
rotarod tests, swimming speed in MWM tests, open field tests, elevated plus maze
tests, treadmill tests and forced swimming tests. The results reveal that the
cognitive deficits are not the results of animal's anxiety or confounding motor
impairments. Overall, the present paradigm appears suitable for the preclinical
evaluation of the long-term effects of pharmacological treatments on ischemic
stroke. Meanwhile, SAA might have therapeutic potential for the treatment of
memory deficits associated with ischemic stroke.
PMID- 28490881
TI - Risk of obstructive sleep apnea and excessive daytime sleepiness in hospitalized
psychiatric patients.
AB - OBJECTIVES: This study evaluated the risk of developing obstructive sleep apnea
(OSA) and excessive daytime sleepiness (EDS) in hospitalized psychiatric patients
at the American University of Beirut Medical Center (AUB-MC). Factors associated
with OSA and EDS occurrence in this sample were also examined. METHODS: The
Berlin questionnaire and the Epworth sleepiness scale; which respectively
evaluate OSA and EDS symptoms, were administered to individuals hospitalized at
an acute psychiatric treatment unit at the AUB-MC between the dates of January
2014 and October 2016. Additional data collected included general demographics,
psychiatric diagnoses, and questionnaires evaluating depression and anxiety
symptoms. Statistical analyses utilizing SPSS were performed to determine the
prevalence of OSA and EDS, as well as their respective associations with patient
profiles. RESULTS: Our results showed that 39.5% of participants were found to
have a high risk of sleep apnea and 9.9% of the participants were found to have
abnormal daytime sleepiness. The risk of developing OSA was associated with a
higher body mass index (BMI) (P=0.02), and depression severity (patient health
questionnaire 9 score) (P=0.01). Increasing severity of depressive symptoms was
associated with a higher risk of sleep apnea (P=0.01). BMI (odds ratio [OR]
=5.97, 95% confidence interval [CI] 1.89-18.82) and depression severity (OR
=4.04, 95% CI 1.80-9.07) were also found to be predictors of OSA. The psychiatric
diagnoses of the participants were not found to have a significant association
with the risk of sleep apnea. CONCLUSION: The risk of OSA is increased among
hospitalized psychiatric patients, and this condition can have detrimental
effects on psychiatric patients. OSA appears to be under-recognized in this
population, psychiatrists should screen for OSA in hospitalized psychiatric
patients and refer them for diagnostic testing or treatment when indicated.
PMID- 28490882
TI - Connectivity to computers and the Internet among patients with schizophrenia
spectrum disorders: a cross-sectional study.
AB - PURPOSE: Information and communication technologies have been developed for a
variety of health care applications and user groups in the field of health care.
This study examined the connectivity to computers and the Internet among patients
with schizophrenia spectrum disorders (SSDs). PATIENTS AND METHODS: A cross
sectional survey design was used to study 311 adults with SSDs from the inpatient
units of two psychiatric hospitals in Finland. The data collection lasted for 20
months and was done through patients' medical records and a self-reported,
structured questionnaire. Data analysis included descriptive statistics. RESULTS:
In total, 297 patients were included in this study (response rate =96%). More
than half of them (n=156; 55%) had a computer and less than half of them (n=127;
44%) had the Internet at home. Of those who generally had access to computers and
the Internet, more than one-fourth (n=85; 29%) used computers daily, and >30%
(n=96; 33%) never accessed the Internet. In total, approximately one-fourth of
them (n=134; 25%) learned to use computers, and less than one-third of them
(n=143; 31%) were known to use the Internet by themselves. Older people (aged 45
65 years) and those with less years of education (primary school) tended not to
use the computers and the Internet at all (P<0.001), and younger people and those
with higher education were associated with more active use. CONCLUSION: Patients
had quite good access to use computers and the Internet, and they mainly used the
Internet to seek information. Social, occupational, and psychological functioning
(which were evaluated with Global Assessment of Functioning) were not associated
with access to and frequency of computer and the Internet use. The results
support the use of computers and the Internet as part of clinical work in mental
health care.
PMID- 28490883
TI - Retrospective analysis of non-laboratory-based adverse drug reactions induced by
intravenous radiocontrast agents in a Joint Commission International-accredited
academic medical center hospital in China.
AB - The authors retrospectively analyzed the pattern and characteristics of non
laboratory-based adverse drug reactions (ADRs) induced by intravenous
radiocontrast agents in a large-scale hospital in China during 2014-2015. There
were 314 ADR cases among 118,208 patients receiving enhanced CT or MRI
examinations. The frequency of moderate/severe ADRs defined by Chinese Society of
Radiology (ie, severe vomiting, systematic urticaria, facial swelling, dyspnea,
vasovagal reaction, laryngeal edema, seizure, trembling, convulsions,
unconsciousness, shock, death, and other unexpected adverse reactions) was rare
(0.0431%), whereas the mild ADRs were uncommon (0.2225%) and accounted for 83.76%
of ADRs. Frequency of ADRs induced by iodinated contrast agents was related with
examination site, sex, and type of patient settings (P<0.01) and was higher
compared with gadolinium contrast agents (0.3676% vs 0.0504%, P<0.01). From 2014
to 2015, frequencies of total and moderate/severe ADRs induced by iodinated
contrast agents decreased significantly (0.4410% vs 0.2947%, P<0.01; 0.0960% vs
0.0282%, P<0.01, respectively). Frequency of ADRs differed among different
iodinated contrast and gadolinium contrast (P<0.05) agents. Iopromide's ADR
frequency in 2014 was significantly higher compared with iopamidol, ioversol, or
iohexol (P<0.01). Frequency of moderate/severe ADRs induced by iodixanol was 4.1
5.4 times that of iohexol, iopromide, or iopamidol. Rash was the predominant ADR
subtype (84.39%) and occurred more frequently with iodixanol compared with
iohexol, iopamidol, or ioversol (P<0.01). Overall, 21.97% of ADR cases had
allergy history or atopy traits, and these cases experienced ADRs earlier than
the negative ones (17.19 min vs 85.34 min, P<0.01). The mean time to onset of
ADRs was increased in patients receiving iodixanol compared with other iodinated
contrast agents (323.77 min vs 42.36 min, P<0.01). Overall, 37.26% of ADRs
occurred within 5 min and 84.08% of ADRs occurred within 30 min. Efficient
quality improvement in decreasing ADRs induced by radiocontrast agents has been
achieved by multidisciplinary collaboration.
PMID- 28490884
TI - Narrowband ultraviolet B light treatment changes plasma concentrations of MMP-3,
MMP-9 and TIMP-3 in psoriatic patients.
AB - BACKGROUND: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs)
are thought to be associated with the pathogenesis and spread of psoriatic
disease. This study was designed to investigate the plasma levels of MMP-3, MMP-9
and TIMP-3 in plaque psoriasis patients prior to and following a course of
ultraviolet B narrowband treatment with respect to disease advancement. METHODS:
Plasma samples of 49 patients suffering from plaque psoriasis and 40 healthy
volunteers were evaluated. Concentrations of MMP-3, MMP-9 and TIMP-3 were
determined using enzyme-linked immunosorbent assay, while Psoriasis Area and
Severity Index was used to define disease advancement. RESULTS: Plasma levels of
MMP-3, MMP-9 and TIMP-3 were significantly elevated in psoriasis patients
compared to healthy individuals. A course of ultraviolet B narrowband treatment
resulted in a significant decline in the studied metalloproteinases. Furthermore,
the concentration of selected tissue inhibitors was negatively correlated with
baseline Psoriasis Area and Severity Index score. CONCLUSION: Our research
highlights the meaningful role of MMP-3, MMP-9 and TIMP-3 in psoriasis
pathogenesis and clearance of disease symptoms. Furthermore, plasma levels of the
analyzed metalloproteinases seem to be a valuable psoriasis biomarker.
PMID- 28490885
TI - Treatment-related severe and fatal adverse events with molecular targeted agents
in the treatment of advanced gastric cancer: a meta-analysis.
AB - AIM: To perform a systematic review and meta-analysis of Phase III randomized
controlled trials (RCTs) to determine the incidence and risk of severe adverse
events (AEs) with molecular targeted agents (MTAs) in advanced/metastatic gastric
cancer (GC) patients. METHODS: A comprehensive literature search for related
trials published up to December 2015 was performed. Eligible studies were Phase
III RCTs of advanced/metastatic GC patients assigned to MTAs or control group.
Data were extracted by two authors for severe and fatal AEs (FAEs). RESULTS: A
total of nine Phase III RCTs involved 4,934 GC patients were ultimately
identified. The pooled results demonstrated that the addition of TAs to therapies
in advanced GC significantly increased the risk of developing severe AEs
(relative risk: 1.12, 95% confidence interval: 1.02-1.24, P=0.02), but not for
FAEs (relative risk: 0.97, 95% confidence interval: 0.65-1.45, P=0.88).
Additionally, the most common causes of FAEs with MTAs were infections (16.3%),
gastrointestinal hemorrhage (8.2%), and arterial thromboembolic events (8.2%),
respectively. CONCLUSION: With available evidence, the use of TAs in GC patients
was associated with an increased risk of severe AEs, but not for FAE. Clinicians
should be aware of the risk of severe AEs with the administration of these drugs
in these patients.
PMID- 28490886
TI - Apatinib to combat EGFR-TKI resistance in an advanced non-small cell lung cancer
patient with unknown EGFR status: a case report.
AB - Lung adenocarcinoma is the most common pathological pattern of lung cancer.
During the past decades, a number of targeted agents have been explored to treat
advanced lung adenocarcinoma. In the present clinical practice, antagonists of
the epidermal growth factor receptor (EGFR) and vascular endothelial growth
factor (VEGF)-directed therapies are widely used. In the former category, the
agent erlotinib (tyrosine kinase inhibitor) has shown obvious advantages over
cytotoxic therapy. Anti-VEGF therapy bevacizumab used for lung adenocarcinoma was
recommended in NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) as
first-line therapy. Similarly, apatinib is speculated to response by selectively
inhibiting the vascular endothelial growth factor receptor-2. The patient with
unknown EGFR status benefited 5-month progressive free survival (PFS) from
erlotinib, and then another 5.1-month PFS with combined treatment of apatinib,
which suggested a new option for lung adenocarcinoma. However, when dabigatran
was used to cancer-related venous thromboembolism during apatinib therapy,
extensive subcutaneous bleeding occurred, warning us against the risks of
bleeding. Besides, hypertension and anorexia were observed, causing dosage
adjustment.
PMID- 28490887
TI - Role of CT scan in differentiating the type of colorectal cancer.
AB - OBJECTIVES: Most colorectal cancers are classical adenocarcinomas (AC), and less
frequent subtypes include mucinous adenocarcinomas (MAC) and signet-ring cell
carcinomas (SC). The purpose of this study was to evaluate the computed
tomography (CT) findings that can help to differentiate MAC and SC from AC.
METHODS: CT scans of 168 patients with pathologically proven MAC and 67 patients
with pathologically proven SC were analyzed, and 220 patients with classical AC
were also included as a control group. CT findings of the three groups were
compared and contrasted in terms of the bowel involvement patterns, contrast
enhancement patterns, and presence or absence of bowel obstruction, intratumoral
calcification, pericolic fat infiltration, and local tumor extension to adjacent
organs. Statistical analyses were made by using the one-way analysis of variance,
least significant difference test, and Pearson's chi-square test. RESULTS:
Compared with classical AC, the MAC showed more severe (6.29+/-2.69 cm vs 4.57+/
1.74 cm, P<0.001) and higher percentage of occurrence of eccentric bowel-wall
thickening (37.2% vs 11.5%, P<0.001). Heterogeneous contrast enhancement was most
common in MAC (P<0.01), and MAC showed more areas with hypoattenuation (P<0.001).
The presence of intratumoral calcification was most frequent in MAC (17.9% vs 2%
vs 6.8%) (P<0.001); the SC also were more severe (5.75+/-2.28 cm vs 4.57+/-1.74
cm. P=0.001) than AC, but SC tend to show more cases of concentric even bowel
wall thickening (67.2%); homogeneous contrast enhancement was most common in SC
(P<0.01), and it showed a target appearance. The presence of peritoneal seeding
was most frequent in SC (35.8% vs 8% vs 2.7%, P<0.001), while the presence of
regional lymph node metastasis (P=0.190) and direct invasion of adjacent organs
or metastasis (P=0.323) were not significantly different among them. CONCLUSION:
Some radiological features by CT can be used to classify different colon tumor
types.
PMID- 28490888
TI - Maintenance therapy with all-trans retinoic acid and arsenic trioxide improves
relapse-free survival in adults with low- to intermediate-risk acute
promyelocytic leukemia who have achieved complete remission after consolidation
therapy.
AB - BACKGROUND: Currently, the optimal maintenance therapy for patients with acute
promyelocytic leukemia (APL) who have achieved complete remission (CR) after
completing consolidation chemotherapy remains controversial. The comparative
effectiveness of the all-trans retinoic acid (ATRA) plus arsenic trioxide (As2O3)
maintenance strategy with classic ATRA plus chemotherapy has not been evaluated.
In this study, we compared the efficacy and toxicity of maintenance therapy with
ATRA plus As2O3 and classic ATRA plus chemotherapy in low- to intermediate-risk
APL patients reaching the first CR after induction and consolidation therapy.
METHODS: A retrospective review of 58 adult patients diagnosed with APL was
conducted. After receiving consolidation therapy and achieving CR, 30 patients
were administered maintenance therapy with an ATRA plus As2O3 regimen (ATRA+As2O3
group), whereas 28 patients were administered 3-monthly cycles of an ATRA plus
chemotherapy regimen (ATRA+chemotherapy group). RESULTS: Grade 3-4 neutropenia
was significantly more frequent in the ATRA+chemotherapy group (N=9, 32.1%) than
in the ATRA+As2O3 group (N=0) (P=0.001). At a median follow-up of 49.1 months
(range: 9.7-97.4 months) from the completion of consolidation, no relapses were
observed in the ATRA+As2O3 group, whereas seven relapses occurred in the
ATRA+chemotherapy group. The risk of relapse in the patients administered
ATRA+As2O3 maintenance was significantly lower than that in those administered
ATRA+chemotherapy maintenance (P=0.004). Based on log-rank analysis, only
maintenance therapy with ATRA and As2O3 was associated with a significantly
higher relapse-free survival (P=0.0159). CONCLUSION: Maintenance therapy with
ATRA and As2O3 was beneficial in low- to intermediate-risk APL patients who were
effectively treated to achieve CR. Further clinical trials with reliable designs
are needed to confirm these observations.
PMID- 28490890
TI - Erratum: B-cell-specific Moloney murine leukemia virus integration site 1:
potential stratification factor and therapeutic target for epithelial ovarian
cancer [Corrigendum].
AB - [This corrects the article on p. 5203 in vol. 9, PMID: 27578986.].
PMID- 28490889
TI - Identification of potential biomarkers and analysis of prognostic values in head
and neck squamous cell carcinoma by bioinformatics analysis.
AB - The purpose of this study was to find disease-associated genes and potential
mechanisms in head and neck squamous cell carcinoma (HNSCC) with deoxyribonucleic
acid microarrays. The gene expression profiles of GSE6791 were downloaded from
the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were
obtained with packages in R language and STRING constructed protein-protein
interaction (PPI) network of the DEGs with combined score >0.8. Subsequently,
module analysis of the PPI network was performed by Molecular Complex Detection
plugin and functions and pathways of the hub gene in subnetwork were studied.
Finally, overall survival analysis of hub genes was verified in TCGA HNSCC
cohort. A total of 811 DEGs were obtained, which were mainly enriched in the
terms related to extracellular matrix (ECM)-receptor interaction, ECM structural
constituent, and ECM organization. A PPI network was constructed, consisting of
401 nodes and 1,254 edges and 15 hub genes with high degrees in the network. High
expression of 4 genes of the 15 genes was associated with poor OS of patients in
HNSCC, including PSMA7, ITGA6, ITGB4, and APP. Two significant modules were
detected from the PPI network, and the enriched functions and pathways included
proteasome, ECM organization, and ECM-receptor interaction. In conclusion, we
propose that PSMA7, ITGA6, ITGB4, and APP may be further explored as potential
biomarkers to aid HNSCC diagnosis and treatment.
PMID- 28490891
TI - No genetic relationship between TLR2 rs4696480, rs3804100, and rs3804099 gene
polymorphisms and female breast cancer in Saudi populations.
AB - Breast cancer (BC) is the most common cause of cancer-related deaths among women
in the Kingdom of Saudi Arabia. An association between the dysregulation of
innate immunity, primarily the deregulation of Toll-like receptors (TLRs), and BC
development was described a long time ago. Several studies have reported that BC
risk factors appear to be related to the interaction between certain genes and
exposure to various environmental factors. Here, we investigated the potential
correlation of three TLR2 single-nucleotide polymorphisms (SNPs; rs3804100,
rs4696480, and rs3804099) with the development of BC in female patients from
Saudi Arabia. We collected 126 blood samples from women with BC and 146 blood
samples from healthy women without any clinical signs of BC. The genotypic
frequencies of TLR2 polymorphisms were assayed. Our results showed that the
genotypic and allelic frequencies of TLR2 did not differ significantly between BC
patients and healthy controls. However, the distributions of rs3804100 (1350 T/C)
genotypes in BC groups were 1%, 19%, and 80% for CC, CT, and TT, respectively. In
the control group, the rs3804100 (1350 T/C) genotype distributions were 3%, 18%,
and 79% for CC, CT, and TT, respectively. The SNP rs3804100 homozygous "TT"
genotype was not associated with the risk of developing BC in the BC patients
compared with controls (odds ratio [OR], 4.5; confidence interval [CI], 0.49
41.02; P=0.145). The TLR2 rs4696480 AA genotype was observed in 23% of BC
patients compared to 18% of control individuals, the AT genotype was seen in 40%
of BC patients and 46% of control individuals, and the TT genotype was observed
in 37% of BC patients and 36% of normal controls. Our results did not show any
difference in genotypic frequency between BC patients and normal controls for the
TLR2 rs3804099 SNP; however, the (C) phenotypic frequency was 49% in BC patients
and 53% in controls. The (T) phenotypic frequency was 51% and 47% in BC patients
and normal patients, respectively. These findings indicate that there is no
association between the TLR2 polymorphisms tested and BC susceptibility in the
female population from the Kingdom of Saudi Arabia. We suggest using other TLR2
SNPs to investigate the possible relationship between innate immunity
deregulation by disruption of TLR2 and potential BC development.
PMID- 28490892
TI - The effectiveness of EGFR-TKIs against brain metastases in EGFR mutation-positive
non-small-cell lung cancer.
AB - Brain metastases are usual in non-small-cell lung cancer (NSCLC) with poor
prognosis and few available therapeutic options. This retrospective study aims to
evaluate the efficacy of epidermal growth factor receptor-tyrosine kinase
inhibitors (EGFR-TKIs) against brain metastases from NSCLC harboring activating
EGFR mutation. A total of 148 patients with brain metastases from EGFR mutation
positive NSCLC were analyzed retrospectively. The patients were orally given
gefitinib (250 mg) or erlotinib (150 mg) once a day until intracranial disease
progression, death, or intolerable side effects. A survival analysis was done
using the Kaplan-Meier analysis and log-rank test. Objective response rate and
disease control rate within brain lesions were 36.5% and 87.2%, respectively,
with a median progression-free survival (PFS) and overall survival (OS) of 11.2
months (95% confidence interval [CI], 10.1-12.3) and 13.6 months (95% CI, 12.3
14.9), respectively. The patients' characteristics were not statistically
associated with PFS and OS. EGFR-TKIs showed promising antitumor activity against
brain metastases in NSCLC patients with activating EGFR mutation and might be the
treatment choice in this clinical setting.
PMID- 28490894
TI - Uniform-related infection control practices of dental students.
AB - BACKGROUND: Uniform-related infection control practices are sometimes overlooked
and underemphasized. In Saudi Arabia, personal protective equipment must meet
global standards for infection control, but the country's Islamic legislature
also needs to be taken into account. AIM: To assess uniform-related infection
control practices of a group of dental students in a dental school in Saudi
Arabia and compare the results with existing literature related to cross
contamination through uniforms in the dental field. METHOD: A questionnaire was
formulated and distributed to dental students at King Abdulaziz University
Faculty of Dentistry in Jeddah, Saudi Arabia, which queried the students about
their uniform-related infection control practices and their methods and frequency
of laundering and sanitizing their uniforms, footwear, and name tags. RESULTS:
There is a significant difference between genders with regard to daily uniform
habits. The frequency of uniform washing was below the standard and almost 30% of
students were not aware of how their uniforms are washed. Added to this, there is
no consensus on a unified uniform for male and female students. CONCLUSION:
Information on preventing cross-contamination through wearing uniforms must be
supplied, reinforced, and emphasized while taking into consideration the cultural
needs of the Saudi society.
PMID- 28490893
TI - Sesame allergy: current perspectives.
AB - Sesame is an important global allergen affecting ~0.1% of the North American
population. It is a major cause of anaphylaxis in the Middle East and is the
third most common food allergen in Israel. We conducted a systematic review of
original articles published in the last 10 years regarding the diagnosis and
management of sesame allergy. Skin prick testing appears to be a useful predictor
of sesame allergy in infants, although data are less consistent in older children
and adults. The diagnostic capacity of serum-specific immunoglobulin E is poor,
especially in studies that used oral food challenges to confirm the diagnosis.
Double-blind, placebo-controlled food challenge thus remains the diagnostic gold
standard for sesame allergy. The cornerstone of sesame allergy management is
allergen avoidance, though accidental exposures are common and patients must be
prepared to treat the consequent reactions with epinephrine. Novel diagnostic and
treatment options such as component-resolved diagnostics, basophil activation
testing, and oral immunotherapy are under development but are not ready for
mainstream clinical application.
PMID- 28490895
TI - Healthcare resource consumption and cost of care among patients with polycystic
kidney disease in Italy.
AB - OBJECTIVE: The aim of this study was to assess healthcare resource consumption
and its associated costs among patients with polycystic kidney disease (PKD) in a
real-world setting. METHODS: An observational retrospective cohort analysis was
conducted using data from the administrative databases of four Italian local
health units. Data for patients who were diagnosed with PKD during the inclusion
period (January 1, 2010 to December 31, 2012) were extracted. The date on which a
patient's first PKD hospitalization occurred during the inclusion period was
defined as the index date (ID), and the ID was defined as the date of the first
dialysis treatment recorded during the inclusion period for patients undergoing
dialysis. Data regarding the clinical characteristics of patients included in the
study during the 12 months prior to the ID (pre-ID; characterization period) were
collected. All patients were then followed up for the 12 months following the ID
(post-ID; follow-up period). Healthcare consumption and its associated costs were
analyzed during the follow-up period. All costs are reported in euros (?).
RESULTS: A total of 1,123 patients with PKD were included in this study, 61.9% of
whom were male; the mean age of the patients was 57.7+/-24.5 years. At diagnosis,
11.2% and 1.1% of patients were affected by the dominant and recessive forms of
PKD, respectively. Approximately 8% of the included patients were undergoing
dialysis at ID (baseline). The incidence of dialysis was fourfold greater among
patients with autosomal-dominant PKD (ADPKD) than among the total cohort (33.3%
compared with an overall 8.3%). During the follow-up period, the average annual
rates of healthcare resource consumption were greater among dialyzed than non
dialyzed patients. The average healthcare expenditures were ?45,059.62 and
?3,913.89 (p<0.001) per year for dialyzed and non-dialyzed PDK patients,
respectively. Our findings suggest that in the real-world Italian context,
consumption of healthcare among patients with PKD has increased at dialysis
initiation due to the cost of outpatient specialist healthcare services as well
as other costs. Research on the prevention of PKD-related complications and
disease progression may help to facilitate a decrease in the costs associated
with this condition.
PMID- 28490896
TI - Granuloma annulare: relationship to diabetes mellitus, thyroid disorders and
tuberculin skin test.
AB - BACKGROUND: Granuloma annulare is a benign inflammatory disease of the skin. The
etiology and pathogenesis of the disease are not yet determined, but some authors
have proposed that it might be associated with a variety of underlying conditions
such as thyroid disorders, diabetes mellitus and positive tuberculin skin test.
OBJECTIVE: This study was conducted to find the probable relationship between
granuloma annulare and diabetes mellitus, thyroid disorders and positive
tuberculin skin test. PATIENTS AND METHODS: A total of 28 patients with granuloma
annulare were recruited from our dermatology outpatient clinic, and data on sex,
age and distribution of granuloma annulare lesions were collected. Forty-one age-
and sex-matched apparently healthy volunteers serving as controls were also
included. Thyroid stimulating hormone (TSH), fasting blood sugar (FBS) and
tuberculin skin tests were performed for both groups. RESULTS: Mean serum level
of FBS in the patient group was significantly higher than the mean serum level of
FBS in the control group (110.60+/-46.31 mg/dL versus 88.39+/-10.58 mg/dL,
respectively, p=0.004). Mean serum level of TSH in the patient group was 3.43+/
2.73 mIU/L, which was not significantly different from the mean serum level of
TSH in the control group (3.26+/-2.11 mIU/L, p=0.772). Four individuals in the
patient group and only 1 in the control group had a positive tuberculin skin
test. CONCLUSION: Granuloma annulare patients are better to be assessed for
diabetes mellitus, but the relationship between this skin disease and thyroid
disorders or tuberculin skin test still needs to be investigated.
PMID- 28490897
TI - Glutathione and its antiaging and antimelanogenic effects.
AB - BACKGROUND: Previous studies showed that supplementation of reduced form of
glutathione (GSH, 500 mg/d) has a skin-lightening efficacy in humans. This study
was designed to evaluate the influences of both GSH and oxidized form (GSSG), at
doses lower than 500 mg/d, on improving skin properties. PATIENTS AND METHODS: A
randomized, double-blind, placebo-controlled, parallel, three-arm study was
conducted. Healthy female subjects were equally randomized into three groups and
took GSH (250 mg/d), GSSG (250 mg/d), or placebo orally for 12 weeks. At each
visit at baseline and for 12 weeks, skin features including melanin index,
wrinkles, and other relevant biophysical properties were measured. Blood samples
were collected for safety monitoring. RESULTS: In generalized estimating equation
analyses, melanin index and ultraviolet spots of all sites including face and arm
when given GSH and GSSG tended to be lower than placebo. At some sites evaluated,
subjects who received GSH showed a significant reduction in wrinkles compared
with those taking placebo. A tendency toward increased skin elasticity was
observed in GSH and GSSG compared with placebo. There were no serious adverse
effects throughout the study. CONCLUSION: We showed that oral glutathione, 250
mg/d, in both reduced and oxidized forms effectively influences skin properties.
Overall, glutathione in both forms are well tolerated.
PMID- 28490898
TI - Education and screening for chronic kidney disease in Indian youth: pilot program
results.
AB - BACKGROUND: There is a paucity of information on kidney education and screening
programs in Indian youth. METHODS: Participants (n=2,158) from Chennai colleges
were educated about the kidneys and chronic kidney disease (CKD) and screened in
a pilot program from April to May 2013. This entailed: 1) a presentation and
educational video and 2) an on-site assessment of weight, blood pressure, and
demographic information. Urinalysis (UA) kits were distributed and returned in
<=48 hours. We examined participant characteristics and their association with
dipstick proteinuria using logistic regression. RESULTS: The mean (standard
deviation [SD]) age was 18.9 (1.6) years, and 1,451 (68%) were men. Mean (SD)
body mass index (BMI) was 21.9 (4.3) kg/m2; 745 (36%) had a BMI consistent with
being overweight or obese. Mean (SD) systolic blood pressure (SBP) was 118.7
(13.1) mm Hg, and 94 (5%) of the participants had SBP >=140. Mean (SD) diastolic
blood pressure (DBP) was 70.9 (11.4) mm Hg, with 119 participants (6%) having
>=90 mm Hg. A total of 136 participants had glycosuria (UA>=1+) and 120 (6%) had
proteinuria (UA>=1+). In unadjusted analyses, sex (odds ratio [OR]=1.64
[confidence interval, CI 1.06-2.55]; p=0.026 men vs. women) and age (OR=1.13 per
year [CI 1.01-1.26]; p=0.032) were significantly associated with proteinuria. In
the analysis adjusted for age, sex, SBP, DBP, glycosuria, and BMI, age remained
independently associated with higher odds for proteinuria (OR=1.14 per year [1.02
1.29]; p=0.026). Males showed a trend of higher risk compared with women (OR=1.57
[CI 1.00-2.50]; p=0.051). CONCLUSION: This education and screening pilot program
in a population of college students offers unique opportunities for
identification, education, and early intervention for CKD.
PMID- 28490899
TI - The influence of clinical equipoise and patient preferences on outcomes of
conservative manual interventions for spinal pain: an experimental study.
AB - BACKGROUND: Expected pain relief from treatment is associated with positive
clinical outcomes in patients with musculoskeletal pain. Less studied is the
influence on outcomes related to the preference of patients and providers for a
specific treatment. OBJECTIVES: We sought to determine how provider and patient
preferences for a manual therapy intervention influenced outcomes in individuals
with acutely induced low back pain (LBP). PARTICIPANTS AND METHODS: Pain-free
participants were randomly assigned to one of two manual therapies (joint biased
[JB] or constant touch [CT]) 48 hours after completing an exercise protocol to
induce LBP. Expectations for pain relief and preferences for treatment were
collected at baseline, prior to randomization. Pain relief was assessed using a
100 mm visual analog scale. All study procedures were conducted in a private
testing laboratory at the University of Florida campus. RESULTS: Sixty
participants were included in this study. After controlling for preintervention
pain intensity, the multivariate model included only preintervention pain
(B=0.12, p=0.07) and provider preference (B=3.05, p<0.0001) and explained 35.8%
of the variance in postintervention pain. When determining whether a participant
met his or her expected pain relief, receiving an intervention from a provider
with a strong preference for that intervention increased the odds of meeting a
participant's expected pain relief 68.3 times (p=0.013) compared to receiving any
intervention from a provider with no preference. Receiving JB intervention from
any provider increased the odds of meeting expected relief 29.7 times (p=0.023).
The effect of a participant receiving an intervention they preferred was retained
in the model but did not meet the criteria for a significant contribution.
CONCLUSION: Our primary findings were that participant and provider preferences
for treatment positively influence pain outcomes in individuals with acutely
induced LBP, and joint-biased interventions resulted in a greater chance of
meeting participants' expected outcomes. This is contrary to our hypothesis that
the interaction of receiving an intervention for which a participant had a
preference would result in the best outcome.
PMID- 28490900
TI - Complex management of a patient with refractory primary erythromelalgia lacking a
SCN9A mutation.
AB - A 41-year-old woman presented with burning and erythema in her extremities
triggered by warmth and activity, which was relieved by applying ice. Extensive
workup was consistent with adult-onset primary erythromelalgia (EM). Several
pharmacological treatments were tried including local anesthetics, capsaicin,
ziconotide, and dantrolene, all providing 24-48 hours of relief followed by
symptom flare. Interventional therapies, including peripheral and sympathetic
ganglion blocks, also failed. Thus far, clonidine and ketamine have been the only
effective agents for our patient. Genetic testing was negative for an EM
associated mutation in the SCN9A gene, encoding the NaV1.7 sodium channel,
suggesting a mutation in an alternate gene.
PMID- 28490901
TI - Breast cancer and amyloid bodies: is there a role for amyloidosis in cancer-cell
dormancy?
AB - Breast cancer and Alzheimer's disease (AD) are major causes of death in older
women. Interestingly, breast cancer occurs less frequently in AD patients than in
the general population. Amyloidosis, the aggregation of amyloid proteins to form
amyloid bodies, plays a central role in the pathogenesis of AD and other human
neuropathies by forming intracellular fibrillary proteins. Contrary to popular
belief, amyloidosis is a common occurrence in mammalian cells, and has recently
been reported to be a natural physiological process in response to environmental
stress stimulations (such as pH and temperature extremes, hypoxia, and oxidative
stress). Many proteins contain an intrinsic "amyloid-converting motif", which
acts in conjunction with a specific noncoding RNA to induce formation of
proteinaceous amyloid bodies that are stored in intracellular bundles. In cancer
cells such as breast and prostate, the process of amyloidosis induces cells to
enter a dormant or resting stage devoid of cell division and proliferation.
Therefore, cancer cells undergo growth cessation and enter a dormant stage
following amyloidosis in the cell; this is akin to giving the cell AD to cease
growth.
PMID- 28490902
TI - Patient and physician preferences for anticancer drugs for the treatment of
metastatic colorectal cancer: a discrete-choice experiment.
AB - OBJECTIVE: Many publications describe preferences for colorectal cancer (CRC)
screening; however, few studies elicited preferences for anticancer-drug
treatment for metastatic CRC (mCRC). This study was designed to elicit
preferences and risk tolerance among patients and oncologists in the USA for
anticancer drugs to treat mCRC. MATERIALS AND METHODS: Patients aged 18 years or
older with a self-reported diagnosis of mCRC and board-certified (or equivalent)
oncologists who had treated patients with mCRC were recruited by two survey
research companies from existing online patient panels in the USA. Additional
oncologists were recruited from a list of US physicians. Patients and oncologists
completed a discrete-choice experiment (DCE) survey. DCEs offer a systematic
method of eliciting preferences and quantifying both the relative importance of
treatment attributes and the tradeoffs respondents are willing to make among
benefits and risks. Treatment attributes in the DCE were progression-free
survival (PFS) and risks of severe papulopustular rash, serious hemorrhage,
cardiopulmonary arrest, and gastrointestinal perforation. Patients' and
physicians' maximum levels of acceptable treatment-related risks for two
prespecified increases in efficacy were estimated. RESULTS: A total of 127
patients and 150 oncologists completed the survey. Relative preferences for the
treatment attributes in the study were mostly consistent with the expectation
that better clinical outcomes were preferred over worse clinical outcomes. Risk
tolerance varied between patients and physicians. On average, physicians were
willing to tolerate higher risks than patients, although these differences were
mostly not statistically significant. Post hoc latent-class analyses revealed
that some patients and physicians were unwilling to forgo any efficacy to avoid
toxicities, while others were willing to make such tradeoffs. CONCLUSION:
Differences in preferences between patients and physicians suggest that there is
the potential for improvement in patients' well-being. Initiating or enhancing
discussions about patient tolerance for toxicities, such as skin rash and
gastrointestinal perforations, may help prescribe treatments that entail more
appropriate benefit-risk tradeoffs.
PMID- 28490903
TI - Cardiovascular risks in smokers treated with nicotine replacement therapy: a
historical cohort study.
AB - BACKGROUND: Previous research suggests exposure to nicotine replacement therapy
(NRT) may be associated with an increased risk of cardiovascular disease (CVD).
METHODS: Using data from the United Kingdom's Clinical Practice Research
Datalink, this study aimed to evaluate CVD events and survival among individuals
who attempted smoking cessation with the support of NRT compared with those aided
by smoking cessation advice only. We studied CVD outcomes over 4 and 52 weeks in
50,214 smokers attempting to quit - 33,476 supported by smoking cessation advice
and 16,738 with the support of NRT prescribed by their primary care physician.
Patients were matched (2 smoking cessation advice patients:1 NRT patient) on
demographic and clinical characteristics during a baseline year preceding their
quit attempt. Cox proportional hazard regression, conditional negative binomial
regression model, and conditional logistic regression were used to analyze data.
RESULTS: Mean (standard deviation) population age was 47 (11.2) years; 51% were
females. Time to first diagnosis of ischemic heart disease (IHD) among NRT and
smoking cessation advice patients was similar within the first 4 weeks, but
shorter for NRT patients over 52 weeks (hazard ratio [HR]: 1.35, 95% confidence
interval [CI]: 1.03-1.77). A similar trend was observed for cerebrovascular
disease (HR: 1.54, 95% CI: 1.08-2.19). NRT patients with a prior diagnosis of IHD
or cerebrovascular disease had a higher rate of primary or secondary care
consultations for IHD or cerebrovascular disease by 52 weeks (rate ratio: 1.50,
95% CI: 1.14-1.99). Patients prescribed NRT had a shorter survival time over 52
weeks, compared with those receiving advice only (HR: 1.39, 95% CI: 1.09-1.76).
CONCLUSION: Our findings suggest that treatment with NRT over 4 weeks does not
appear to have an impact on cardiovascular risks. However, a longer follow-up
period of 52 weeks resulted in an increase in cardiovascular events for patients
prescribed NRT, compared with those receiving smoking cessation advice only.
PMID- 28490904
TI - Clinical epidemiology in the era of big data: new opportunities, familiar
challenges.
AB - Routinely recorded health data have evolved from mere by-products of health care
delivery or billing into a powerful research tool for studying and improving
patient care through clinical epidemiologic research. Big data in the context of
epidemiologic research means large interlinkable data sets within a single
country or networks of multinational databases. Several Nordic, European, and
other multinational collaborations are now well established. Advantages of big
data for clinical epidemiology include improved precision of estimates, which is
especially important for reassuring ("null") findings; ability to conduct
meaningful analyses in subgroup of patients; and rapid detection of safety
signals. Big data will also provide new possibilities for research by enabling
access to linked information from biobanks, electronic medical records, patient
reported outcome measures, automatic and semiautomatic electronic monitoring
devices, and social media. The sheer amount of data, however, does not eliminate
and may even amplify systematic error. Therefore, methodologies addressing
systematic error, clinical knowledge, and underlying hypotheses are more
important than ever to ensure that the signal is discernable behind the noise.
PMID- 28490905
TI - Reproductive and hormonal risk factors of breast cancer: a historical
perspective.
AB - The complexity of breast cancer etiology has puzzled scientists for more than 300
years. In this brief review, we emphasize the importance of reproductive and
hormonal factors in relation to the risk of breast cancer. By following the
historical course of how various risk factors have been determined, this study
attempts to illustrate the origin of hypotheses, their subsequent rejection, and
development of new hypotheses. Starting with the contributions of Italian
physicians in the 18th century and covering the activity of British
epidemiologists before World War II, this review ends up with the international
collaboration that became increasingly important in the second half of the 20th
century.
PMID- 28490906
TI - In vivo antiplasmodial activity evaluation of the leaves of Balanites
rotundifolia (Van Tiegh.) Blatter (Balanitaceae) against Plasmodium berghei.
AB - Balanites rotundifolia (BR) (Van Tiegh.) Blatter (Balanitaceae) has been used in
Ethiopian folk medicine to treat malaria, despite the lack of scientific
validation. Therefore, the present study was carried out to evaluate the
antiplasmodial activity of 80% methanol leaf extract of BR in mice. Both the 4
day suppressive test and Rane's test were employed. Three extract doses (BR100
mg/kg, BR200 mg/kg, and BR400 mg/kg/d) were given orally, and chloroquine was the
standard drug administered through the same route. Outcome measures for
evaluating antiplasmodial efficacy were parasitemia level, packed cell volume,
survival time, and body temperature as well as body weight change. Moreover,
preliminary phytochemical and acute toxicity studies were carried out. With the 4
day suppressive test, BR demonstrated dose-dependent significant reduction in
parasitemia level at all test doses compared to the negative control: BR400 (67%,
P<0.001), BR200 (42%, P<0.01), and BR100 (37%, P<0.05). With Rane's test as well,
BR significantly (P<0.001 for all test doses) reduced the parasitemia level by
38% (BR100), 45% (BR200), and 69% (BR400) in comparison to vehicle treatment. The
crude extract was estimated to have oral median lethal dose higher than 2,000
mg/kg, and the presence of alkaloids and cardiac glycosides was confirmed.
Therefore, this study for the first time validated the antiplasmodial activity of
crude leaf extract of BR. Further investigations for isolating specific
phytochemicals and elucidating mechanisms are needed to address the quest for
novel antimalarial drugs.
PMID- 28490907
TI - Perspective on the Rezum(r) System: a minimally invasive treatment strategy for
benign prostatic hyperplasia using convective radiofrequency water vapor thermal
therapy.
AB - Convective radiofrequency (RF) water vapor thermal therapy is a minimally
invasive office or outpatient procedure for the treatment of bothersome moderate
to-severe lower urinary tract symptoms associated with benign prostatic
hyperplasia (BPH). It provides an option for patients seeking rapid and durable
relief of urinary symptoms, improved quality of life, and preservation of sexual
function as an alternative to long-term use of drugs and avoidance of the
potential side effects of pharmaceuticals or invasive BPH surgery. The procedure
is also applicable for the treatment of the median lobe or elevated bladder neck
from central zone hyperplasia. This perspective presents a comprehensive overview
of the Rezum(r) System convective RF thermal therapy device, the principles upon
which it is based, the operative procedure, and the clinical evidence accrued to
this point in time.
PMID- 28490908
TI - Effects of prophylactic ankle and knee braces on leg stiffness during hopping.
AB - During human movement, the leg can be represented as a mechanical spring, with
its stiffness potentially contributing to sports performance and injury
prevention. Although many individuals perform athletic activities with joint
stabilizers, little is known about the effects of prophylactic lower extremity
braces on leg stiffness. The objective of this study was to investigate the
effect of ankle and/or knee braces on leg stiffness measured during one-legged
hopping at a range of frequencies. Thirteen male participants performed one
legged hopping with their dominant leg at frequencies of 2.2, 2.6, and 3.0 Hz.
All participants were randomly tested under the following four brace conditions:
1) no brace (control), 2) prophylactic ankle brace, 3) prophylactic knee brace,
and 4) prophylactic ankle and knee braces. Based on a spring-mass model, leg
stiffness was calculated using data from an accelerometer. It was found that leg
stiffness increased with increasing hopping frequency for each brace condition.
However, there were no significant differences in leg stiffness among the four
brace conditions at the three hopping frequencies. Since some level of leg
stiffness is needed for optimal athletic performance and training, these results
suggest that ankle and knee braces do not significantly interfere with dynamic
hopping activities.
PMID- 28490909
TI - Determining early referral criteria for patients with suspected inflammatory
arthritis presenting to primary care physicians: a cross-sectional study.
AB - OBJECTIVE: Early diagnosis and initiation of treatment for inflammatory arthritis
can greatly improve patient outcome. We aimed to provide standardized and
validated criteria for use by primary care physicians (PCPs) in the
identification of individuals requiring referral to a rheumatologist. PATIENTS
AND METHODS: We analyzed the predictive value of a wide variety of demographic
variables, patient-reported complaints, physical examination results, and
biomarkers in order to identify the most useful factors for indicating a
requirement for referral. Patients for this cross-sectional study were enrolled
from various centers of the city of Jeddah, Saudi Arabia, if they were >=18 years
of age and presented to a PCP with small joint pain that had been present for
more than 6 weeks. A total of 203 patients were enrolled, as indicated by the
sample size calculation. Each patient underwent a standardized physical
examination, which was subsequently compared to ultrasound findings. Biomarker
analysis and a patient interview were also carried out. Results were then
correlated with the final diagnosis made by a rheumatologist. RESULTS: A total of
9 variables were identified as having high specificity and good predictive value:
loss of appetite, swelling of metacarpophalangeal joint 2 or 5, swelling of
proximal inter-phalangeal joint 2 or 3, wrist swelling, wrist tenderness, a
positive test for rheumatoid factor, and a positive test for anti-citrullinated
protein antibodies. CONCLUSION: Nine variables should be the basis of early
referral criteria. It should aid PCPs in making appropriate early referrals of
patients with suspected inflammatory arthritis, accelerating diagnosis and
initiation of treatment.
PMID- 28490911
TI - The effect of physical activity on sleep quality, well-being, and affect in
academic stress periods.
AB - The stress-buffering hypothesis postulates that physical activity and exercise
can buffer the negative effects of (academic) stress on health. It still remains
an open question whether students, who regularly engage in physical activity and
exercise within their academic examination period, can successfully diminish
these negative effects. Sixty-four subjects participated in this study and
completed a total of five surveys, with T1 at the end of the semester break
(baseline) and T2-T5 being presented every Friday in the last 4 weeks of the
semester (examination period). They were asked to answer questions about their
activity level, sleep quality, well-being and affect. Hierarchical linear models
showed significant dependencies on time for all dependent measures. The expansion
of the model for exercise also showed significant main effects of this predictor
on well-being and positive affect (PA) and negative affect. Moreover, significant
interactions with time for sleep quality and PA were found. Results suggest that
physical activity and exercise in the academic examination period may be able to
buffer the negative effects of stress on health-related outcomes. Therefore,
activity levels should be maintained in times of high stress to prevent negative
effects on sleep, well-being and affect in students.
PMID- 28490910
TI - Optimizing psychosocial interventions in first-episode psychosis: current
perspectives and future directions.
AB - Psychotic-spectrum disorders such as schizophrenia, schizoaffective disorder, and
bipolar disorder with psychotic features are devastating illnesses accompanied by
high levels of morbidity and mortality. Growing evidence suggests that outcomes
for individuals with psychotic-spectrum disorders can be meaningfully improved by
increasing the quality of mental health care provided to these individuals and
reducing the delay between the first onset of psychotic symptoms and the receipt
of adequate psychiatric care. More specifically, multicomponent treatment
packages that 1) simultaneously target multiple symptomatic and functional needs
and 2) are provided as soon as possible following the initial onset of psychotic
symptoms appear to have disproportionately positive effects on the course of
psychotic-spectrum disorders. Yet, despite the benefit of multicomponent care for
first-episode psychosis, clinical and functional outcomes among individuals with
first-episode psychosis participating in such services are still suboptimal.
Thus, the goal of this review is to highlight putative strategies to improve care
for individuals with first-episode psychosis with specific attention to
optimizing psychosocial interventions. To address this goal, we highlight four
burgeoning areas of research with regard to optimization of psychosocial
interventions for first-episode psychosis: 1) reducing the delay in receipt of
evidence-based psychosocial treatments; 2) synergistic pairing of psychosocial
interventions; 3) personalized delivery of psychosocial interventions; and 4)
technological enhancement of psychosocial interventions. Future research on these
topics has the potential to optimize the treatment response to evidence-based
psychosocial interventions and to enhance the improved (but still suboptimal)
treatment outcomes commonly experienced by individuals with first-episode
psychosis.
PMID- 28490912
TI - Update on the treatment of narcolepsy: clinical efficacy of pitolisant.
AB - Narcolepsy is a neurological disease that affects 1 in 2,000 individuals and is
characterized by excessive daytime sleepiness (EDS). In 60-70% of individuals
with narcolepsy, it is also characterized by cataplexy or a sudden loss of muscle
tone that is triggered by positive or negative emotions. Narcolepsy decreases the
quality of life of the afflicted individuals. Currently used drugs treat EDS
alone (modafinil/armodafinil, methylphenidate, and amphetamine), cataplexy alone
("off-label" use of antidepressants), or both EDS and cataplexy (sodium oxybate).
These drugs have abuse, tolerability, and adherence issues. A greater diversity
of drug options is needed to treat narcolepsy. The small molecule drug,
pitolisant, acts as an inverse agonist/antagonist at the H3 receptor, thus
increasing histaminergic tone in the wake promoting system of the brain.
Pitolisant has been studied in animal models of narcolepsy and used in clinical
trials as a treatment for narcolepsy. A comprehensive search of online databases
(eg, Medline, PubMed, EMBASE, the Cochrane Library Database, Ovid MEDLINE, Europe
PubMed Central, EBSCOhost CINAHL, ProQuest Research Library, Google Scholar, and
ClinicalTrials.gov) was performed. Nonrandomized and randomized studies were
included. This review focuses on the outcomes of four clinical trials of
pitolisant to treat narcolepsy. These four trials show that pitolisant is an
effective drug to treat EDS and cataplexy in narcolepsy.
PMID- 28490913
TI - Health-related quality of life among cognitively intact nursing home residents
with and without cancer - a 6-year longitudinal study.
AB - BACKGROUND: Limited information exists regarding the natural development of
health-related quality of life (HRQOL) and its determinants among mentally intact
nursing home (NH) residents. We aimed to examine HRQOL over time during a 6-year
period among residents of NHs, who are not cognitively impaired, and to examine
whether sense of coherence and a diagnosis of cancer influence HRQOL. METHODS:
The study was prospective and included baseline assessment and 6-year follow-up.
After baseline assessment of 227 cognitively intact NH residents (Clinical
Dementia Rating score <= 0.5), we interviewed 52 living respondents a second time
at the 5-year follow-up and 18 respondents a third time at the 6-year follow-up.
We recorded data from the interviews using the Short Form-36 (SF-36) Health
Survey and the Sense of Coherence Scale. To study different developments over
time for residents without and with cancer, we tested interactions between cancer
and time. RESULTS: The subscores of physical functioning and role limitation
physical domains declined with time (P < 0.001 and P = 0.02, respectively).
Having a diagnosis of cancer at baseline was negatively correlated with general
health (P = 0.002). Sense of coherence at baseline was positively correlated with
all the SF-36 subscores from baseline to follow-up (P < 0.001). CONCLUSION: The
study indicates that the HRQOL changed over time during the 6 years of follow-up,
and the sense of coherence appeared to be an important component of the HRQOL.
Finally, our results showed that having a diagnosis of cancer was associated with
decline in the general health subdimension.
PMID- 28490914
TI - Assessment of residency program outcomes via alumni surveys.
AB - BACKGROUND: One trend in medical education is outcomes-oriented training.
Outcomes usually refer to individuals' acquisition of competencies, for example,
during training in residency programs. However, little is known about outcomes of
these programs. In order to fill this gap, human resource (HR) data were analyzed
and alumni of a pediatric residency program were surveyed at the Department of
Pediatrics, Bern University Hospital, Switzerland. METHODS: Residency program
outcomes (demographics, career choices, part-time or full-time work status,
competencies, feedback) were assessed through in-house HR databases, publicly
available data on the Internet (physician directory and practice homepages), and
2 alumni surveys (S1, S2). RESULTS: In all, 109 alumni met the inclusion
criteria. Retention rate at the hospital was low (14%). Forty-six alumni (42%) in
private practice were eligible for alumni surveys. Response rates were 87% (S1)
and 61% (S2). Time intervals between 2 career decisions (selecting specialty of
pediatrics vs selecting setting of private practice) varied widely (late-training
decision to enter private practice). Mean employment level in private practice
was 60% (range 20%-100%). Most valued rotation was emergency medicine; most
desired competencies in future colleagues were the ability to work in a team,
proficiency in pediatrics, and working economically. CONCLUSION: A broadened view
on outcomes - beyond individuals' competency acquisition - provides informative
insights into a training program, can allow for informed program updates, and
guide future program development.
PMID- 28490915
TI - Older patients have increased risk of poor outcomes after low-velocity pedestrian
motor vehicle collisions.
AB - BACKGROUND: Motor vehicle collisions (MVCs) are a leading cause of injury in the
US. While the probability of collision with a pedestrian (PMVC) has declined in
recent years, the probability of a pedestrian fatality has risen. Our objective
was to determine whether older age impacts potential outcomes in patients
involved in low-velocity PMVCs. MATERIALS AND METHODS: We performed a
retrospective-cohort study of adult patients aged >14 years involved in low
velocity pedestrian-MVCs (<15 miles per hour [24.14 km/h]), presenting to an
urban level I trauma center from January to November 2013. Subjects were
identified via trauma registry and stratified: ages 15-49 years and >=50 years.
Electronic medical records were reviewed for demographics, vital signs, and
laboratory results on initial presentation, presence or absence of systemic
inflammatory response syndrome (SIRS), shock index (SI), injury-severity score
(ISS), length of stay (LOS), and survival to discharge. For statistical analysis,
chi2 or Student's t-tests were utilized. RESULTS: Our study included 145 patients
(77 female) with a mean age of 41.9+/-3 years; 95 patients were aged 15-49 years
(mean 31.9+/-2.2 years), and 50 patients were aged >=50 years or older (mean
62.44+/-2.9 years). Mean ISS was 10.05+/-1.95, mean SI was 0.68+/-0.03, and mean
LOS was 3.67+/-0.57 days. A total of 41 patients met SIRS criteria on arrival,
and nine patients expired (6.2%). Mean ISS (15.64+/-4.42 vs 7.1+/-1.64, P<0.001)
and mean SI (0.75+/-0.07 vs 0.65+/-0.03, P=0.002) were higher in patients aged
>=50 years. Mean LOS was longer in older patients (5.22+/-1.14 vs 2.85+/-0.58
days, P<0.001). Older age was associated with SIRS on arrival (P=0.023) and
associated with mortality (P=0.004). CONCLUSION: Age >=50 years is associated
with greater severity of injury and poor outcomes for patients involved in low
velocity PMVCs. Increased clinical attention and resource allocation should be
directed toward older patients after low-velocity PMVCs.
PMID- 28490916
TI - The cannabis withdrawal syndrome: current insights.
AB - The cannabis withdrawal syndrome (CWS) is a criterion of cannabis use disorders
(CUDs) (Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition)
and cannabis dependence (International Classification of Diseases [ICD]-10).
Several lines of evidence from animal and human studies indicate that cessation
from long-term and regular cannabis use precipitates a specific withdrawal
syndrome with mainly mood and behavioral symptoms of light to moderate intensity,
which can usually be treated in an outpatient setting. Regular cannabis intake is
related to a desensitization and downregulation of human brain cannabinoid 1
(CB1) receptors. This starts to reverse within the first 2 days of abstinence and
the receptors return to normal functioning within 4 weeks of abstinence, which
could constitute a neurobiological time frame for the duration of CWS, not taking
into account cellular and synaptic long-term neuroplasticity elicited by long
term cannabis use before cessation, for example, being possibly responsible for
cannabis craving. The CWS severity is dependent on the amount of cannabis used
pre-cessation, gender, and heritable and several environmental factors.
Therefore, naturalistic severity of CWS highly varies. Women reported a stronger
CWS than men including physical symptoms, such as nausea and stomach pain.
Comorbidity with mental or somatic disorders, severe CUD, and low social
functioning may require an inpatient treatment (preferably qualified detox) and
post-acute rehabilitation. There are promising results with gabapentin and delta
9-tetrahydrocannabinol analogs in the treatment of CWS. Mirtazapine can be
beneficial to treat CWS insomnia. According to small studies, venlafaxine can
worsen the CWS, whereas other antidepressants, atomoxetine, lithium, buspirone,
and divalproex had no relevant effect. Certainly, further research is required
with respect to the impact of the CWS treatment setting on long-term CUD
prognosis and with respect to psychopharmacological or behavioral approaches,
such as aerobic exercise therapy or psychoeducation, in the treatment of CWS. The
up-to-date ICD-11 Beta Draft is recommended to be expanded by physical CWS
symptoms, the specification of CWS intensity and duration as well as gender
effects.
PMID- 28490918
TI - The two solitudes of primary care and cancer specialist care: is there a bridge?
PMID- 28490919
TI - Clinician participation in CADTH's pan-Canadian Oncology Drug Review:
contribution and impact on cancer drug funding recommendations.
PMID- 28490917
TI - From caveman companion to medical innovator: genomic insights into the origin and
evolution of domestic dogs.
AB - The phenotypic and behavioral diversity of the domestic dog has yet to be matched
by any other mammalian species. In their current form, which comprises more than
350 populations known as breeds, there is a size range of two orders of magnitude
and morphological features reminiscent of not only different species but also
different phylogenetic families. The range of both appearance and behavior found
in the dog is the product of millennia of human interference, and though humans
created the diversity it remains a point of fascination to both lay and
scientific communities. In this review we summarize the current understanding of
the history of dog domestication based on molecular data. We will examine the
ways that canine genetic and genomic studies have evolved and look at examples of
dog genetics in the light of human disease.
PMID- 28490920
TI - The role of family physicians in cancer care: perspectives of primary and
specialty care providers.
AB - BACKGROUND: Currently, the specific role of family physicians (fps) in the care
of people with cancer is not well defined. Our goal was to explore physician
perspectives and contextual factors related to the coordination of cancer care
and the role of fps. METHODS: Using a constructivist grounded theory approach, we
conducted telephone interviews with 58 primary and cancer specialist health care
providers from across Canada. RESULTS: The participants-21 fps, 15 surgeons, 12
medical oncologists, 6 radiation oncologists, and 4 general practitioners in
oncology-were asked to describe both the role that fps currently play and the
role that, in their opinion, fps should play in the future care of cancer
patients across the cancer continuum. Participants identified 3 key roles:
coordinating cancer care, managing comorbidities, and providing psychosocial care
to patients and their families. However, fps and specialists discussed many
challenges that prevent fps from fully performing those roles: ? The fps
described communication problems resulting from not being kept "in the loop"
because they weren't copied on patient reports and also the lack of clearly
defined roles for all the various health care providers involved in providing
care to cancer patients.? The specialists expressed concerns about a lack of
patient access to fp care, leaving specialists to fill the care gaps. The fps and
specialists both recommended additional training and education for fps in
survivorship care, cancer screening, genetic testing, and new cancer treatments.
CONCLUSIONS: Better communication, more collaboration, and further education are
needed to enhance the role of fps in the care of cancer patients.
PMID- 28490921
TI - Use of physician services during the survivorship phase: a multi-province study
of women diagnosed with breast cancer.
AB - INTRODUCTION: Oncologists have traditionally been responsible for providing
routine follow-up care for cancer survivors; in recent years, however, primary
care providers (pcps) are taking a greater role in care during the follow-up
period. In the present study, we used a longitudinal multi-province retrospective
cohort study to examine how primary care and specialist care intersect in the
delivery of breast cancer follow-up care. METHODS: Various databases (registry,
clinical, and administrative) were linked in each of four provinces: British
Columbia, Manitoba, Ontario, and Nova Scotia. Population-based cohorts of breast
cancer survivors were identified in each province. Physician visits were
identified using billings or claims data and were classified as visits to primary
care (total, breast cancer-specific, and other), oncology (medical oncology,
radiation oncology, and surgery), and other specialties. The mean numbers of
visits by physician type and specialty, or by combinations thereof, were
examined. The mean numbers of visits for each follow-up year were also examined
by physician type. RESULTS: The results showed that many women (>64%) in each
province received care from both primary care and oncology providers during the
follow-up period. The mean number of breast cancer-specific visits to primary
care and visits to oncology declined with each follow-up year. Interprovincial
variations were observed, with greater surgeon follow-up in Nova Scotia and
greater primary care follow-up in British Columbia. Provincial differences could
reflect variations in policies and recommendations, relevant initiatives, and
resources or infrastructure to support pcp-led follow-up care. CONCLUSIONS:
Optimizing the role of pcps in breast cancer follow-up care might require
strategies to change attitudes about pcp-led follow-up and to better support pcps
in providing survivorship care.
PMID- 28490922
TI - A population-based assessment of primary care visits during adjuvant chemotherapy
for breast cancer.
AB - BACKGROUND: We used administrative health data to explore the impact of primary
care physician (pcp) visits on acute-care service utilization by women receiving
adjuvant chemotherapy for early-stage breast cancer (ebc). METHODS: Our
population-based retrospective cohort study examined pcp visits and acute-care
use [defined as an emergency room (er) visit or hospitalization] by women
diagnosed with ebc between 2007 and 2009 and treated with adjuvant chemotherapy.
Multivariate regression analysis was used to identify the effect of pcp visits on
the likelihood of experiencing an acute-care visit. RESULTS: Patients receiving
chemotherapy visited a pcp significantly more frequently than they had before
their diagnosis [relative risk (rr): 1.48; 95% confidence interval (ci): 1.44 to
1.53; p < 0.001] and significantly more frequently than control subjects without
cancer (rr: 1.51; 95% ci: 1.46 to 1.57; p < 0.001). More than one third of pcp
visits by chemotherapy patients were related to breast cancer or chemotherapy
related side effects. In adjusted multivariate analyses, the likelihood of
experiencing an er visit or hospitalization increased in the days immediately
after a pcp visit (rr: 1.92; 95% ci: 1.76 to 2.10; p < 0.001). CONCLUSIONS:
During chemotherapy treatment, patients visited their pcp more frequently than
control subjects did, and they visited for reasons related to their breast cancer
or to chemotherapy-related side effects. Visits to a pcp by patients receiving
chemotherapy were associated with an increased frequency of er visits or
hospitalizations in the days immediately after the pcp visit. Those results
suggest an opportunity to institute measures for early detection and intervention
in chemotherapy side effects.
PMID- 28490923
TI - Multigene expression profile testing in breast cancer: is there a role for family
physicians?
AB - BACKGROUND: Family physicians (fps) play a role in aspects of personalized
medicine in cancer, including assessment of increased risk because of family
history. Little is known about the potential role of fps in supporting cancer
patients who undergo tumour gene expression profile (gep) testing. METHODS: We
conducted a mixed-methods study with qualitative and quantitative components.
Qualitative data from focus groups and interviews with fps and cancer specialists
about the role of fps in breast cancer gep testing were obtained during studies
conducted within the pan-Canadian canimpact research program. We determined the
number of visits by breast cancer patients to a fp between the first medical
oncology visit and the start of chemotherapy, a period when patients might be
considering results of gep testing. RESULTS: The fps and cancer specialists felt
that ordering gep tests and explaining the results was the role of the
oncologist. A new fp role was identified relating to the fp-patient relationship:
supporting patients in making adjuvant therapy decisions informed by gep tests by
considering the patient's comorbid conditions, social situation, and preferences.
Lack of fp knowledge and resources, and challenges in fp-oncologist communication
were seen as significant barriers to that role. Between 28% and 38% of patients
visited a fp between the first oncology visit and the start of chemotherapy.
CONCLUSIONS: Our findings suggest an emerging role for fps in supporting patients
who are making adjuvant treatment decisions after receiving the results of gep
testing. For success in this new role, education and point-of-care tools,
together with more effective communication strategies between fps and
oncologists, are needed.
PMID- 28490924
TI - Improving molecular testing and personalized medicine in non-small-cell lung
cancer in Ontario.
AB - BACKGROUND: Although molecular testing has become standard in managing advanced
nonsquamous non-small-cell lung cancer (nsclc), most patients undergo minimally
invasive procedures, and the diagnostic tumour specimens available for testing
are usually limited. A knowledge translation initiative to educate diagnostic
specialists about sampling techniques and laboratory processes was undertaken to
improve the uptake and application of molecular testing in advanced lung cancer.
METHODS: A multidisciplinary panel of physician experts including pathologists,
respirologists, interventional thoracic radiologists, thoracic surgeons, medical
oncologists, and radiation oncologists developed a specialty-specific education
program, adapting international clinical guidelines to the local Ontario context.
Expert recommendations from the program are reported here. RESULTS: Panel experts
agreed that specialists procuring samples for lung cancer diagnosis should choose
biopsy techniques that maximize tumour cellularity, and that conservation
strategies to maximize tissue for molecular testing should be used in tissue
processing. The timeliness of molecular reporting can be improved by pathologist
initiated reflex testing upon confirmation of nonsquamous nsclc and by prompt
transportation of specimens to designated molecular diagnostic centres. To
coordinate timely molecular testing and optimal treatment, collaboration and
communication between all clinicians involved in diagnosing patients with
advanced lung cancer are mandatory. CONCLUSIONS: Knowledge transfer to diagnostic
lung cancer specialists could potentially improve molecular testing and treatment
for advanced lung cancer patients.
PMID- 28490926
TI - Challenges and insights in implementing coordinated care between oncology and
primary care providers: a Canadian perspective.
AB - We report here on the current state of cancer care coordination in Canada and
discuss challenges and insights with respect to the implementation of
collaborative models of care. We also make recommendations for future research.
This work is based on the findings of the Canadian Team to Improve Community
Based Cancer Care Along the Continuum (canimpact) casebook project. The casebook
project identified models of collaborative cancer care by systematically
documenting and analyzing Canadian initiatives that aim to improve or enhance
care coordination between primary care providers and oncology specialists. The
casebook profiles 24 initiatives, most of which focus on breast or colorectal
cancer and target survivorship or follow-up care. Current key challenges in
cancer care coordination are associated with establishing program support,
engaging primary care providers in the provision of care, clearly defining
provider roles and responsibilities, and establishing effective project or
program planning and evaluation. Researchers studying coordinated models of
cancer care should focus on designing knowledge translation strategies with
updated and refined governance and on establishing appropriate protocols for both
implementation and evaluation.
PMID- 28490925
TI - Management of EGFR-mutated non-small-cell lung cancer: practical implications
from a clinical and pathology perspective.
AB - Starting in the early 2000s, non-small-cell lung cancer (nsclc) subtypes have
evolved from being histologically described to molecularly defined. Management of
lung adenocarcinomas now generally requires multiple molecular tests at baseline
to define the optimal treatment strategy. More recently, second biopsies
performed at progression in patients treated with tyrosine kinase inhibitors
(tkis) have further defined the continued use of molecularly targeted therapy. In
the present article, we focus on one molecular subtype: EGFR-mutated nsclc. For
that patient population, multiple lines of tki therapy are now available either
clinically or in clinical trials. Each line of treatment is guided by the
specific mutations (for example, L858R, T790M, C797S) identified in EGFR. We
first describe the various mechanisms of acquired resistance to EGFR tki
treatment. We then focus on strategies that clinicians and pathologists can both
use during tissue acquisition and handling to optimize patient results. We also
discuss future directions for the molecular characterization of lung cancers with
driver mutations, including liquid biopsies. Finally, we provide an algorithm to
guide treating physicians managing patients with EGFR-mutated nsclc. The same
framework can also be applied to other molecularly defined nsclc subgroups as
resistance patterns are elucidated and additional lines of treatment are
developed.
PMID- 28490927
TI - How different is cancer control across Canada? Comparing performance indicators
for prevention, screening, diagnosis, and treatment.
AB - Meaningful performance measures are an important part of the toolkit for health
system improvement. The Canadian Partnership Against Cancer has been reporting on
pan-Canadian cancer system performance indicators since 2009-work that has led to
the availability of standardized measures that can help to shed light on the
extent of variation and opportunities for quality improvement across the country.
Those measures include a core set of system indicators ranging from prevention
and screening, through diagnosis and treatment, to survivorship and end-of-life
care. Key indicators were calculated and graphed, showing the range from worst to
best result for the provinces and territories included in the data. There were
often significant differences in cancer system performance between provinces and
territories. For example, smoking prevalence rates ranged from 14% to 62%. The
90th percentile wait times from an abnormal breast screen to resolution (without
biopsy) ranged from 4 weeks to 8 weeks. The percentage of breast cancer
resections that used breast-conserving surgery rather than mastectomy ranged from
38% to 75%. Clinical trial participation rates for adults ranged from 0.2% to
6.6%. Variations in performance indicators between Canadian jurisdictions suggest
potential differences in the planning and delivery of cancer control services and
in clinical practice patterns and patient outcomes. Understanding sources of
variation can help to identify opportunities for improvements in the quality and
outcomes of cancer control service delivery in each province and territory.
PMID- 28490928
TI - Synthesis maps: visual knowledge translation for the CanIMPACT clinical system
and patient cancer journeys.
AB - Salient findings and interpretations from the canimpact clinical cancer research
study are visually represented in two synthesis maps for the purpose of
communicating an integrated presentation of the study to clinical cancer
researchers and policymakers. Synthesis maps integrate evidence and expertise
into a visual narrative for knowledge translation and communication. A clinical
system synthesis map represents the current Canadian primary care and cancer
practice systems, proposed as a visual knowledge translation from the mixed
methods canimpact study to inform Canadian clinical research, policy, and
practice discourses. Two synthesis maps, drawn together from multiple canimpact
investigations and sources, were required to articulate critical differences
between the clinical system and patient perspectives. The synthesis map of Canada
wide clinical cancer systems illustrates the relationships between primary care
and the full cancer continuum. A patient-centred map was developed to represent
the cancer (and primary care) journeys as experienced by breast and colorectal
cancer patients.
PMID- 28490929
TI - Ovarian cancer in Manitoba: trends in incidence and survival, 1992-2011.
AB - BACKGROUND: Because the International Cancer Benchmarking Partnership, in a study
of diagnosis years between 1995 and 2007, showed lower-than-expected survival for
Manitoba's ovarian cancer patients, we undertook an analysis to describe the
features of ovarian cancer diagnosed in Manitoba during a 20-year period. We also
determined the most recent trends in survival to see if the previous results were
sustained. METHODS: In this retrospective cohort study, ovarian cancer cases
diagnosed during 1992-2011 were extracted from the Manitoba Cancer Registry. The
incidence of ovarian cancer was calculated for the overall group and for age,
morphology, residence, treatment, and stage. Trends over time, with a particular
focus on changes that might correlate with poor survival, were analyzed. The 1-
and 3-year relative survival rates were also calculated. RESULTS: The incidence
of ovarian cancer did not vary over time (p = 0.640), even when stratified by age
or morphology groups. Use of adjuvant chemotherapy decreased (p = 0.005) and use
of neoadjuvant chemotherapy increased over time (p = 0.002). Diagnoses of stage
iv cancers declined over time (p < 0.020). Trends in incidence did not coincide
with previously observed decreases in relative survival. CONCLUSIONS: A decline
in diagnoses of stage iv ovarian cancer could be responsible for a recent
increase in relative survival. However, sample size might have limited power in
some analyses, and the previously reported decrease in relative survival might
have been due to a random fluctuation in the data. Future efforts will focus on
continued monitoring of the patterns of ovarian cancer presentation and outcomes
in Manitoba.
PMID- 28490930
TI - Metformin and breast cancer stage at diagnosis: a population-based study.
AB - PURPOSE: The objective of the present study was to use a large, population-based
cohort to examine the association between metformin and breast cancer stage at
diagnosis while accounting for mammography differences. METHODS: We used data
from Ontario administrative health databases to identify women 68 years of age or
older with diabetes and invasive breast cancer diagnosed from 1 January 2007 to
31 December 2012. Adjusted logistic regression models were used to compare breast
cancer stage at diagnosis (stages i and ii vs. iii and iv) between the women
exposed and not exposed to metformin. We also examined the association between
metformin use and estrogen receptor status, tumour size, and lymph node status in
the subset of women for whom those data were available. RESULTS: We identified
3125 women with diabetes and breast cancer; 1519 (48.6%) had been exposed to
metformin before their cancer diagnosis. Median age at breast cancer diagnosis
was 76 years (interquartile range: 72-82 years), and mean duration of diabetes
was 8.8 +/- 5.9 years. In multivariable analyses, metformin exposure was not
associated with an earlier stage of breast cancer (odds ratio: 0.98; 95%
confidence interval: 0.81 to 1.19). In secondary analyses, metformin exposure was
not associated with estrogen receptor-positive breast cancer, tumours larger than
2 cm, or positive lymph nodes. CONCLUSIONS: This population-based study did not
show an association between metformin use and breast cancer stage or tumour
characteristics at diagnosis. Our study considered older women with long-standing
diabetes, and therefore further studies in younger patients could be warranted.
PMID- 28490931
TI - Treatment and outcomes for glioblastoma in elderly compared with non-elderly
patients: a population-based study.
AB - PURPOSE: Elderly patients make up a large percentage of the individuals newly
diagnosed with glioblastoma (gbm), but they face particular challenges in
tolerating standard therapy, and compared with younger patients, they experience
significantly shorter survival. We set out to compare clinical characteristics,
treatment patterns, and outcomes in a non-elderly group (<65 years) and an
elderly group (>=65 years) of patients diagnosed with gbm. METHODS: This
retrospective population-based study used a province-wide cancer registry to
identify patients with a new diagnosis of gbm within a 6-year period (2006-2012).
Of the 138 patients identified, 56 (40.6%) were 65 years of age or older.
Demographic characteristics, treatment patterns, and overall survival (os) in the
elderly and non-elderly groups were compared. Predictors of os were determined
using multivariate analysis. RESULTS: Elderly patients were more likely to
present with a poor performance status (Eastern Cooperative Oncology Group >= 2),
to undergo biopsy without resection, and to receive whole-brain or
hypofractionated radiotherapy. Compared with non-elderly patients, the elderly
patients were less likely to receive adjuvant temozolomide. Survival time was
significantly shorter in the elderly than in the non-elderly patients (7.2 months
vs. 11.2 months). In multivariate analysis, surgical resection, hypofractionated
radiotherapy (compared with whole-brain or conventional radiotherapy), and
chemotherapy were predictive of os in older patients. Among elderly patients
receiving radiation, survival was improved with the use of combined therapy
compared with the use of radiation only (11.3 months vs. 4.6 months).
CONCLUSIONS: Overall survival was shorter for elderly patients with gbm than for
non-elderly patients; the elderly patients were also less likely to receive
intensive surgical or adjuvant therapy. Our population-based analysis
demonstrated improved os with surgical resection, hypofractionated radiotherapy,
and temozolomide, and supports the results of recent clinical trials
demonstrating a benefit for combination chemoradiotherapy in older patients.
PMID- 28490932
TI - Contextualizing the use of oncologic imaging within treatment phases: imaging
trends and modality preferences, 2000-2014.
AB - BACKGROUND: In the present study, we retrospectively evaluated the use of
tomographic imaging in adult cancer patients to clarify how recent growth
plateaus in the use of tomographic imaging in the United States might have
affected oncologic imaging during the same period. METHODS: At a U.S. academic
cancer centre, 12,059 patients with dates of death from January 2000 through
December 2014 were identified. Imaging was restricted to brain and body computed
tomography (ct), brain and body magnetic resonance (mr), and body positron
emission tomography (pet) with and without superimposed ct. Trends during the
staging (1 year after diagnosis), monitoring (18-6 months before death), and end
of-life (final 6 months before death) phases were analyzed. RESULTS: Comparing
the 2005-2009 with the 2010-2014 period, mean intensity of pet imaging increased
21% during staging (p = 0.0000) and 27% during end of life (p = 0.0019). In the
monitoring phase, mean intensity for ct brain, ct body, and mr body imaging
decreased by 26% (p = 0.0133), 11% (p = 0.0118), and 26% (p = 0.0008),
respectively. Aggregate mean intensity of imaging increased in the 13%-27% range
every 3 months from 18 months before death to death, reaching 1.43 images in the
final 3 months of life. Patients diagnosed in the final 18 months of life had an
average of 1 additional image during both the 3 months after diagnosis (p =
0.0000) and the final 3 months before death (p = 0.0000). CONCLUSIONS: Imaging
increased as temporal proximity to death decreased, and patients diagnosed near
death received more staging imaging, suggesting that imaging guidelines should
consider imaging intensity within the context of treatment phase. Despite the
development, by multiple organizations, of appropriateness criteria to reduce
imaging utilization, aggregate per-patient imaging showed insignificant changes.
Simultaneous fluctuations in the intensity of imaging by modality suggest recent
changes in the modalities preferred by providers.
PMID- 28490933
TI - Prognostic and predictive value of low estrogen receptor expression in breast
cancer.
AB - PURPOSE: Anti-hormonal therapy (tamoxifen) is recommended for estrogen receptor
(er)-positive breast cancer (bca); however, its effect on low-receptor cancers is
unclear. We retrospectively evaluated the effect of adjuvant tamoxifen in
patients with weakly er-positive bca. METHODS: We identified 2221 bca patients
who had been er-tested by ligand-based assay (lba) during 1976-1995 and who had
been treated and followed until 2008. Cox proportional hazards models adjusted
for age, body mass index, tumour size, nodal status, surgery, and chemotherapy
were used to assess the effect of er level on bca survival in patients who
received tamoxifen. RESULTS: Overall, 17% (383) of patients were within 0-3
fmol/mg cytosol protein, and 12% (266) were within 4-9 fmol/mg cytosol protein.
Patients with er levels of 0-3, 4-9, 10-19, 20-49, and 50 fmol/mg or more cytosol
protein had 20-year bca survival rates of 56%, 56%, 63%, 71%, and 60%
respectively. Of the 2221 patients studied, 661 (29.8%) received anti-hormonal
therapy. Within the latter group, er levels of 0-3, 4-9, 10-19, 20-49, and 50
fmol/mg or more cytosol protein were associated with a hazard ratio for lower bca
mortality: respectively, 1.00 (reference), 0.59 (p = 0.09), 0.19 (p < 0.0001),
0.26 (p < 0.0001), and 0.31 (p < 0.0001)-the risk reduction being significant
only for er levels of 10 fmol/mg or more cytosol protein. CONCLUSIONS: Tamoxifen
use in bca patients with a weakly positive er status (4-9 fmol/mg cytosol
protein), compared with those having higher er levels (>=10 fmol/mg cytosol
protein), is not associated with a significantly lower bca-specific mortality.
Our results do not support treatment with anti-hormonal therapy for bca patients
with a weakly positive er status as identified by lba.
PMID- 28490934
TI - Factors influencing treatment selection and survival in advanced lung cancer.
AB - PURPOSE: Despite numerous breakthrough therapies, inoperable lung cancer still
places a heavy burden on patients who might not be candidates for chemotherapy.
To identify potential candidates for the newly emerging immunotherapy-based
treatment paradigms, we explored the clinical and biologic factors affecting
treatment decisions. METHODS: We retrospectively reviewed the records of patients
diagnosed at our university-affiliated cancer centre between 1 January 2011 and
31 December 2013. Patient demographics, systemic treatment, and survival were
examined. RESULTS: During the 3-year study period, 683 patients fitting the
inclusion criteria were identified. First-line therapy was administered in 49.5%
of patients; only 22.4% received further lines of therapy. The main reasons for
withholding therapy were poor performance status [ps (43.2%)], rapidly
deteriorating ps (31.9%), patient refusal of therapy (20.9%), and associated
comorbidities (4%). Older age, the presence of brain metastasis at diagnosis, and
non-small-cell histology were also associated with therapeutic restraint.
Oncology referrals were infrequent in patients who did not receive therapy
(32.2%). Older patients and those with a poor ps experienced superior survival
when treatment was administered (hazard ratio: 0.25; 95% confidence interval:
0.16 to 0.38; and hazard ratio: 0.44; 95% confidence interval: 0.23 to 0.87
respectively; p < 0.001). CONCLUSIONS: Advanced lung cancer still poses a
therapeutic challenge, with a high proportion of patients being deemed unfit for
therapy. This issue cannot be resolved until appropriate measures are taken to
ensure the inclusion of older patients and those with a relatively poor ps in
large clinical trials. Immunotherapy might be interesting in this setting, given
that it appears to be more tolerable. Another consequential undertaking would be
the deployment of strategies to reduce wait times during the diagnostic process
for patients with a high index of suspicion for lung cancer.
PMID- 28490935
TI - Characteristics predicting outcomes of allogeneic stem-cell transplantation in
relapsed acute myelogenous leukemia.
AB - BACKGROUND: Allogeneic hematopoietic stem-cell transplantation (ahsct) is
associated with significant morbidity and mortality, but it can cure carefully
selected patients with acute myeloid leukemia (aml) in second remission (cr2). In
a cohort of patients with aml who underwent ahsct in cr2, we determined the pre
transplant factors that predicted for overall survival (os), relapse, and non
relapse mortality. We also sought to validate the prognostic risk groups derived
by Michelis and colleagues in this independent population. METHODS: In a
retrospective chart review, we obtained data for 55 consecutive patients who
underwent ahsct for aml in cr2. Hazard ratios were used to describe the
independent effects of pre-transplant variables on outcome, and Kaplan-Meier
curves were used to assess outcomes in the three prognostic groups identified by
Michelis and colleagues. RESULTS: At 1, 3, and 5 years post-transplant, os was
60%, 45.5%, and 37.5% respectively. Statistically significant differences in os,
relapse mortality, and non-relapse mortality were not identified between the
prognostic risk groups identified by Michelis and colleagues. Women were less
likely than men to relapse, and a modified European Society for Blood and Marrow
Transplantation (mebmt) score of 3 or less was associated with a lower non
relapse mortality. CONCLUSIONS: The 37.5% 5-year os in this cohort suggests that,
compared with other options, ahsct offers patients with aml in cr2 a better
chance of cure. Our study supports the use of the mebmt score to predict non
relapse mortality in this population.
PMID- 28490936
TI - Rising rates of colorectal cancer among younger Iranians: is diet to blame?
AB - BACKGROUND: Colorectal cancer (crc) is one of the most prevalent cancers in the
world. Although the incidence of crc is currently very low in the older Iranian
population compared with Western populations, young Iranians show a rising trend
of crc-that is, the age-adjusted rate is close in the young Iranian population
compared with the U.S. population, and the rate in older Iranians is much lower.
METHODS: To assess a putative relationship between diet and a rising rate of crc
in younger Iranians, a combined text word and mesh heading search strategy
identified relevant studies through Google Scholar and medline. RESULTS: A
critical look at diet among Iranians shows major issues that might be raising the
risk for crc. There are also scenarios other than diet for the rise, such as the
young age structure of the country. However, the actual scenario is more complex.
CONCLUSIONS: In Iran, crc is one of the most common incident cancers and a common
cause of cancer death. Primary and secondary prevention-with attention to a
healthy lifestyle, physical activity, and screening-should be enhanced in the
general population.
PMID- 28490937
TI - Uptake of a 21-gene expression assay in breast cancer practice: views of academic
and community-based oncologists.
AB - PURPOSE: Advances in personalized medicine have produced novel tests and
treatment options for women with breast cancer. Relatively little is known about
the process by which such tests are adopted into oncology practice. The
objectives of the present study were to understand the experiences of medical
oncologists with multigene expression profile (gep) tests, including their
adoption into practice in early-stage breast cancer, and the perceptions of the
oncologists about the influence of test results on treatment decision-making.
METHODS: We conducted a qualitative descriptive study involving interviews with
medical oncologists from academic and community cancer centres or hospitals in 8
communities in Ontario. A 21-gene breast cancer assay was used as the example of
gep testing. Qualitative analytic techniques were used to identify the main
themes. RESULTS: Of 28 oncologists who were approached, 21 (75%) participated in
the study [median age: 43 years; 12 women (57%)]. Awareness and knowledge of gep
testing were derived from several sources: international scientific meetings,
participation in clinical studies, discussions with respected colleagues, and
manufacturer-sponsored meetings. Oncologists observed that incorporating gep
testing into their clinical practice resulted in several changes, including
longer consultation times, second visits, and taking steps to minimize treatment
delays. Oncologists expressed divergent opinions about the strength of evidence
and added value of gep testing in guiding treatment decisions. CONCLUSIONS:
Incorporation of gep testing into clinical practice in early-stage breast cancer
required oncologists to make changes to their usual routines. The opinions of
oncologists about the quality of evidence underpinning the test affected how much
weight they gave to test results in treatment decision-making.
PMID- 28490938
TI - Comparative survival in patients with brain metastases from non-small-cell lung
cancer treated before and after implementation of radiosurgery.
AB - INTRODUCTION: Survival after a diagnosis of brain metastasis in non-small-cell
lung cancer (nsclc) is generally poor. We previously reported a median survival
of approximately 4 months in a cohort of patients treated with whole-brain
radiotherapy (wbrt). Since that time, we implemented a program of stereotactic
radiosurgery (srs). In the present study, we examined survival and prognostic
factors in a consecutive cohort of patients after the introduction of the srs
program. METHODS: Data from a retrospective review of 167 nsclc patients with
brain metastasis referred to a tertiary cancer centre during 2010-2012 were
compared with data from a prior cohort of 91 patients treated during 2005-2007
("pre-srs cohort"). RESULTS: Median overall survival from the date of diagnosis
of brain metastasis (4.3 months in the srs cohort vs. 3.9 months in the pre-srs
cohort, p = 0.74) was not significantly different in the cohorts. The result was
similar when the no-treatment group was excluded from the srs cohort. Within the
srs cohort only, significant differences is overall survival were observed
between treatment groups (srs, wbrt plus srs, wbrt, and no treatment), with
improved survival being observed on univariate and multivariate analysis for
patients receiving srs compared with patients receiving wbrt alone (p < 0.001).
CONCLUSIONS: No improvement in survival was observed for nsclc patients with
brain metastases after the implementation of srs. Selected patients (younger age,
female sex, good performance status, fewer brain metastases) treated with srs
appeared to demonstrate improved survival. However, those observations might also
reflect better patient selection for srs or a greater tendency to offer those
patients systemic therapy in addition to srs.
PMID- 28490939
TI - Measuring quality care in localized renal cell cancer: use of appropriate
preoperative investigations in a population-based cohort.
AB - INTRODUCTION: Obtaining appropriate preoperative risk-specific staging
investigations for localized renal cell carcinoma (rcc) is a recognized quality
indicator. The goal of the present work was to determine the use and
appropriateness of preoperative investigations in patients undergoing curative
surgery for rcc. METHODS: This population-based retrospective study of patients
having surgery for localized rcc recorded the use of preoperative imaging and
laboratory investigations within 6 months of surgery. "Appropriate" stage
specific investigations were determined using recognized published guidelines.
RESULTS: The study cohort consisted of 544 patients with 72.8% being stage i,
18.4% being stage ii, and 8.8% being stage iii by clinical TNM (2002) criteria.
In 61.6%, chest imaging was obtained by chest radiography or computed tomography
(ct) within 3 months preoperatively; in 75.6%, such imaging was obtained within 6
months. Abdominal ct imaging was obtained in 97.1% of patients before surgery,
with 77.5% of patients receiving such imaging within 3 months of surgery.
Complete blood count, electrolytes, and creatinine were measured in 99.1% of
patients, but those tests plus other recommended blood tests including calcium,
alkaline phosphatase, and liver function were measured in only 17.7%.
CONCLUSIONS: In this study, most patients received appropriate abdominal imaging,
but chest imaging was underutilized in the overall cohort. Despite being
recommended, blood tests such as liver function, alkaline phosphatase, and
calcium were completed in fewer than 2 of 10 patients. This analysis provides the
groundwork for quality improvement initiatives directed to the use of
preoperative investigations in localized rcc.
PMID- 28490940
TI - Systemic therapy in the curative treatment of head-and-neck squamous cell cancer:
Cancer Care Ontario clinical practice guideline.
AB - OBJECTIVE: The aim of the present work was to make recommendations about the use
of systemically administered drugs in combination or in sequence with radiation
(rt) or surgery, or both, for cure or organ preservation, or both, in patients
with locally advanced nonmetastatic (stages iii-ivb) squamous cell carcinoma of
the head and neck (lascchn). METHODS: The Meta-analysis of Chemotherapy in Head
and Neck Cancer (mach-nc) reports have, de facto, guided practice since 2000, and
so we searched the literature for systematic reviews published from January 2000
to February 2015 in reference to five research questions. A search was also
conducted up to February 2015 for randomized trials (rcts) not included in the
meta-analyses. Recommendations were constructed using the Cancer Care Ontario
Program in Evidence-Based Care practice guidelines development cycle. RESULTS: In
addition to updated mach-nc reports, five additional meta-analyses and thirty
rcts were identified. Five recommendations for lascchn treatment were generated
based on those data. Concurrent chemoradiation (ccrt) is recommended to maximize
the chance of cure in patients less than 71 years of age when rt is used as
definitive treatment. The same recommendation also applies to patients with
resected lascchn considered to be at high risk for locoregional recurrence. For
lascchn patients who are candidates for organ preservation strategies and would
otherwise require total laryngectomy, either ccrt or induction chemotherapy,
followed by rt or surgery based on tumour response is recommended. The addition
of cetuximab to intensified rt (concomitant boost or hyperfractionated schedule)
is an alternative to ccrt. Routine use of induction chemotherapy to improve
overall survival is not recommended. CONCLUSIONS: We were able to use high-level
evidence from patients receiving rt as definitive or postoperative treatment to
generate recommendations for the use of systemic therapy in the treatment of
lascchn. A limitation is a lack of stratification for human papillomavirus
related cancers of the oropharynx. One rct provided evidence for the use of
cetuximab as an alternative to chemotherapy in the definitive rt setting.
Concurrent chemoradiation provides one strategy for larynx preservation, but the
best strategy is unclear. Use of induction chemotherapy does not improve overall
survival, and its use should be limited to patients requiring immediate tumour
downsizing before local therapy.
PMID- 28490941
TI - Effectiveness of Hypnosis in Combination with Conventional Techniques of Behavior
Management in Anxiety/Pain Reduction during Dental Anesthetic Infiltration.
AB - Background and Objective. Anxiety/pain are experiences that make dental treatment
difficult for children, especially during the time of anesthesia. Hypnosis is
used in pediatric clinical situations to modify thinking, behavior, and
perception as well as, recently, in dentistry; therefore the aim of this study
was to evaluate the effectiveness of hypnosis combined with conventional behavior
management techniques during infiltration anesthetic. Methods. Anxiety/pain were
assessed with the FLACC scale during the anesthetic moment, as well as heart rate
variability and skin conductance before and during the anesthetic moment, between
the control and experimental group. Results. A marginal statistical difference (p
= 0.05) was found in the heart rate between baseline and anesthetic moment, being
lower in the hypnosis group. No statistically significant differences were found
with the FLACC scale or in the skin conductance (p > 0.05). Conclusion. Hypnosis
combined with conventional behavior management techniques decreases heart rate
during anesthetic infiltration showing that there may be an improvement in
anxiety/pain control through hypnotic therapy.
PMID- 28490943
TI - Comparing the performance of granular coral limestone and Leca in adsorbing Acid
Cyanine 5R from aqueous solution.
AB - The effect of granular coral limestone and Leca as adsorbents for removing Acid
Cyanine 5R (AC5R) from aqueous solution was studied. The optimum pH and adsorbent
particles size in both adsorbents were determined to be 3 and 297 MUm,
respectively. The optimum dosages of coral limestone and granular Leca were 0.150
and 0.145 g/mg of dye, respectively. Also, results have shown that the adsorption
efficiency by both coral limestone and Leca increased with the decreasing
adsorbent particles size. Moreover, under similar conditions, the maximum removal
efficiency by granular coral limestone and Leca was 94% and 88%, respectively.
The results revealed that the performance of granular coral limestone was better
in AC5R removal than that of Leca granulated under such condition. In total,
granular coral limestone and Leca act as suitable adsorbents for removing dye
pollutants from an aqueous solution.
PMID- 28490942
TI - Comparison of Incidences of Intravascular Injection between Medial and Lateral
Side Approaches during Traditional S1 Transforaminal Epidural Steroid Injection.
AB - Purpose. Intravascular injection rates are higher during traditional S1
transforaminal epidural steroid injection (TFESI) compared with lumbar
transforaminal injection. We compared the incidences of intravascular injection
between the medial and lateral approaches to the S1 foramen during S1 TFESI.
Materials and Methods. A total of 139 patients underwent one or more TFESIs (170
total injections). The patients received S1 TFESI by either medial or lateral
side of S1 foramen under fluoroscopic anteroposterior view using digital
subtraction method. The intravascular injection rates, epidural spread patterns,
and contrast volumes required to reach the superior aspect of the L5-S1
intervertebral disc (SIVD) were compared between groups. Results. Intravascular
injection rates during S1 TFESI were significantly lower in the medial approach
compared with the lateral approach patients (4.9% versus 38.6%, resp., P <
0.001). The medial approach group had more epidural spread to the L5-S1 SIVD than
the lateral group (82.1% versus 58.8%, resp.); lower contrast volume amounts were
required to extend the L5-S1 SIVD (1.46 +/- 0.48 versus 1.90 +/- 0.62, resp.).
Conclusion. During S1 TFESI, approaching the needle towards the medial part of
the S1 foramen may reduce intravascular injection risk.
PMID- 28490944
TI - Phytochemical evaluation of roots of Plumbago zeylanica L. and assessment of its
potential as a nephroprotective agent.
AB - Search for medicinal plants to treat kidney disorders is an important topic on
phytotherapeutical research. Plumbago zeylanica L. is an important medicinal
plant with hepatoprotective, anti-inflammatory, anti-diabetic, anti-cancer and
anti-hyperlipidemic activities. In the present study, the protective effect of
hydroalcoholic extract of P. zeylanica (HAPZ) in cisplatin induced nephrotoxicity
was analyzed in Swiss albino mice. Treatment with higher dose (400 mg/kg) of HAPZ
significantly reversed the adverse effect of cisplatin on kidney weight, serum
urea and creatinine, indicating their renoprotective effect. The antioxidant
effect of the drug is evident from its significant effect on Catalase,
Glutathione peroxidase and lipid peroxidation activities.
PMID- 28490945
TI - Sanitary impact evaluation of drinking water in storage reservoirs in Moroccan
rural area.
AB - In Morocco, storage reservoirs are particular systems of water supply in rural
areas. These reservoirs are fed with rainwater and/or directly from the river,
which are very contaminated by several pathogenic bacteria. They are used without
any treatment as a drinking water by the surrounding population. In this context,
the aim of this study is to evaluate the impact of consuming contaminated water
stored in reservoirs on health status for six rural communities located in Assif
El Mal, Southern East of Marrakech. This was investigated using a classical
methodology based on population survey and by molecular approach using PCR-DGGE
technique to determine the intestinal bacterial diversity of consumers. The
survey showed that, the residents of the studied area suffered from numerous
health problems (diarrheal diseases, vomiting or hepatitis A) due to the lack of
waste management infrastructures. The consumer's stool analysis by molecular
approach revealed that numbers of Escherichia coli, Aeromonas hydrophila and
Clostridia, were significantly higher in the diarrheal feces. In addition, PCR
DGGE study of the prevalence and distribution of bacteria causing human diseases,
confirmed that, there is a relationship between water bacterial contaminations of
storage reservoirs and microbial disease related health status. Therefore, water
reservoir consumption is assumed to be the mean way of exposure for this
population. It's clear that this approach gives a very helpful tool to confirm
without any doubt the relationship between water bacterial contamination and
health status.
PMID- 28490946
TI - Plant species and communities assessment in interaction with edaphic and
topographic factors; an ecological study of the mount Eelum District Swat,
Pakistan.
AB - The current analyses of vegetation were aimed to study the different effects of
environmental variables and plant species and communities interaction to these
variables, identified threats to local vegetation and suggestion for remedial
measures in the Mount Eelum, Swat, Pakistan. For assessment of environmental
variability quantitative ecological techniques were used through quadrats having
sizes of 2 * 2, 5 * 5 and 10 * 10 m2 for herbs, shrubs and trees respectively.
Result of the present study revealed 124 plant species in the study area.
Canonical Correspondence Analysis (CCA) was used to analyze the ecological
gradient of vegetation. The environmental data and species abundance were used in
CANOCO software version 4.5. The presence absence data of plant species were
elaborated with Cluster and Two Way Cluster Analysis techniques using PC-ORD
version 5 to show different species composition that resulted in five plant
communities. Findings indicate that elevation, aspect and soil texture are the
strongest variables that have significant effect on species composition and
distribution of various communities shown with P value 0.0500. It is recommended
to protect and use sensibly whole of the Flora normally and rare species
particularly in the region.
PMID- 28490948
TI - Preparation and quality evaluation of coenzyme Q10 long-circulating liposomes.
AB - The aim of this work was to prepare coenzyme Q10 (CoQ10) long-circulating
liposomes, and establish the quality standard to determine the content and
entrapment efficiency. CoQ10 long-circulating liposomes were prepared by the film
dispersion method, HPLC assay for the determination of CoQ10 was developed. Free
drugs and liposomes were separated using the protamine aggregation method and
entrapment efficiency was determined. The liposomes were homogeneous and the mean
diameter was 166.0 nm, Zeta potential was -22.2 mV. The content and entrapment
efficiency of CoQ10 were 98.2% and 93.2% for three batches of liposomes,
respectively. The lyophilized form of liposomes prepared by freeze-drying showed
stable quality characteristics during storage. The formulation and preparative
method can be used to prepare CoQ10 long-circulating liposomes with high
entrapment efficiency and high quality, the determination method of drug content
and entrapment efficiency were effective and rapid and can be used for quality
evaluation of liposomes.
PMID- 28490947
TI - Preliminary fabrication and characterization of electron beam melted Ti-6Al-4V
customized dental implant.
AB - The current study was aimed to fabricate customized root form dental implant
using additive manufacturing technique for the replacement of missing teeth. The
root form dental implant was designed using GeomagicTM and MagicsTM, the designed
implant was directly manufactured by layering technique using ARCAM A2TM electron
beam melting system by employing medical grade Ti-6Al-4V alloy powder.
Furthermore, the fabricated implant was characterized in terms of certain
clinically important parameters such as surface microstructure, surface
topography, chemical purity and internal porosity. Results confirmed that,
fabrication of customized dental implants using additive rapid manufacturing
technology offers an attractive method to produce extremely pure form of
customized titanium dental implants, the rough and porous surface texture
obtained is expected to provide better initial implant stabilization and superior
osseointegration.
PMID- 28490949
TI - Function of PD-L1 in antitumor immunity of glioma cells.
AB - Human glioma is a highly fatal tumor with a significant feature of immune
suppression. The functions of PD-L1 refer to co-simulation and immune regulation.
To investigate expression and functional activity of PD-L1 in human glioma cell
in vivo and in vitro. Expressions of PD-L1mRNA and protein in the human glioma
cell line were analyzed with quantitative RT-PCR and flow cytometer; and then
expression of PD-L1 in tissue specimens of 10 glioma patients was treated with
immunohistochemical analysis; glioma cell and allogeneic CD4+ and CD8+ T cells
were co-cultured, and cytokine IFN-gamma, IL-2 and IL-10 in cultured supernatant
fluid were determined with ELISA; upon blocking the interaction between glioma
cell and the immune cell with PD-L1 monoclonal antibody (5H1), surface markers on
immune cells were analyzed using flow cytometer. All human glioma cell lines
constitutively expressed PD-L1, and IFN-gamma induced glioma cell to highly
express PD-L1. It was shown through immunohistochemical analysis that glioma
specimen expressed PD-L1, while expression of PD-L1 was not observed in normal
tissue and normal human brain near the tumor location. The release of IFN-gamma
and IL-2 was inhibited, while IL-10 was increased slightly. Glioma cell may
escape from immune recognition and injury with the help of PD-L1, which is a
significant pathogenic mechanism of glioma.
PMID- 28490950
TI - Self-medication and antibiotic resistance: Crisis, current challenges, and
prevention.
AB - The present study aims to explore the crisis of antibiotic resistance and
discover more about the current challenges related to self-medication. The
current challenges related to antibiotic resistance are unique and differ from
the challenges of the past since new bacterial pathogens are involved and
continue to evolve. Strains with resistance to multiple antibiotic classes have
emerged which the discovery of new antibiotics has failed to match. The
consequences of antibiotic resistance are grave with mortality and morbidity
continually on the rise. This paper also highlights the possible interventions
that can be effective at the micro or individual level in the prevention of
development of antibiotic resistance.
PMID- 28490951
TI - Gene introgression from common wheat into Aegilops L.
AB - Group of experiments were carried out to verify possibility of gene introgression
from common wheat into Aegilops. The artificial indoor crossbreed was conducted
using 7 genotypes from 4 wheat relative species as female, and common wheat as
male. The experiment result shows that different species has variable cross
ability. Among the 4 Aegilops species, the highest cross rate is from the
combination of Aegilops tauschii * Triticum aestivum (46.49% for genotype Ae42,
22.58% for Y92), the second is from Aegilops ovata * T. aestivum (14.76% for
Y100, 12.11% for Ae23), the third is from Aegilops cylindrica * T. aestivum
(2.23% for Ae7, 8.50% for Y145), and the lowest is from Aegilops speltoides * T.
aestivum (0.19%). Hybrid embryos from different combinations have different
ability of callus initiation and germination. The hybrid embryos from A. ovata/T.
aestivum and Ae. tauschii/T. aestivum have a higher level of callus initiation
and germination. Ae. cylindrica/T. aestivum has a middle level, while the Ae.
speltoides has a lower level. The interspecific hybrids between Aegilops and
common wheat have so low fertility. In back-crosses, the seed-set rate of hybrids
of Ae. ovata/T. aestivum is 3.71% and 4.36% respectively back-crossed with male
and female parents, while for hybrids of Ae. cylindrica/T. aestivum, they were 0
and 0.33% respectively, and for Ae. tauschii/T. aestivum, 0.33% and 0
respectively. On selfing of the hybrids, the seed-set rate is 0 (no seed set from
9750 florets) for the combination of Ae. cylindrica/T. aestivum, 0.044% (3 selfed
seeds out of 6870 florets) for Ae. ovata/T. aestivum and 0 (no seed set from 7253
florets) for Ae. tauschii/T. aestivum. The research suggests that the probability
of gene introgression from T. aestivum into Aegilops species is very low in
nature.
PMID- 28490952
TI - Biological activity of Xanthium strumarium seed extracts on different cancer cell
lines and Aedes caspius, Culex pipiens (Diptera: Culicidae).
AB - Effects of methanol extracts of Xanthium strumarium on different cancer cell
lines and on the mortality rates of Aedes caspius, Culex pipiens (Diptera:
Culicidae) were investigated. Among the cell lines tested, the Jurkat cell line
was the most sensitive to the methanol extract and ethyl acetate fraction, with
reported LC50 values of 50.18 and 48.73 MUg/ml respectively. Conversely, methanol
extracts were not that toxic to the A549 cell line though the toxicity increased
on further purification. The percentage of growth inhibition was dose dependent
for the methanol extract and ethyl acetate fraction. The ethyl acetate fraction
showed higher toxicity to all cell lines tested when compared to the methanol
extract. The results showed that methanol extracts of plant seeds caused 100%
mortality of mosquito larvae at a concentration of 1000 MUg/ml after 24 h of
treatment. The LC50 and LC90 values of X. strumarium were found to be 531.07 and
905.95 MUg/ml against Ae. caspius and 502.32 and 867.63 MUg/ml against Cx.
Pipiens, respectively. From the investigations, it was concluded that the crude
extract of X. strumarium showed a weak potential for controlling the larval
instars of Ae. caspius and Cx. pipiens. However, on further purification the
extract lost the larvicidal activity. The ethyl acetate fraction showed higher
toxicity to all cell lines tested when compared to the methanol extract. The
ethyl acetate fraction investigated in this study appears to have a weak
larvicidal activity but a promising cytotoxic activity. Future studies will
include purification and investigation in further detail of the action of X.
strumarium on Cancer Cell Lines and mosquitoes.
PMID- 28490953
TI - Determination of seed viability of eight wild Saudi Arabian species by
germination and X-ray tests.
AB - Our purpose was to evaluate the usefulness of the germination vs. the X-ray test
in determining the initial viability of seeds of eight wild species (Salvia
spinosa, Salvia aegyptiaca, Ochradenus baccatus, Ochradenus arabicus, Suaeda
aegyptiaca, Suaeda vermiculata, Prosopisfarcta and Panicumturgidum) from Saudi
Arabia. Several days were required to determine viability of all eight species
via germination tests, while immediate results on filled/viable seeds were
obtained with the X-ray test. Seeds of all the species, except Sa.aegyptiaca,
showed high viability in both the germination (98-70% at 25/15 degrees C, 93-66%
at 35/25 degrees C) and X-ray (100-75%) test. Furthermore, there was general
agreement between the germination (10% at 25/15 degrees C and 8% at 35/25
degrees C) and X-ray (5%) tests that seed viability of Sa.aegyptiaca was very
low, and X-ray analysis revealed that this was due to poor embryo development.
Seeds of P.farcta have physical dormancy, which was broken by scarification in
concentrated sulfuric acid (10 min), and they exhibited high viability in both
the germination (98% at 25/15 degrees C and 93% at 35/25 degrees C) and X-ray
(98%) test. Most of the nongerminated seeds of the eight species except those of
Sa.aegyptiaca were alive as judged by the tetrazolium test (TZ). Thus, for the
eight species examined, the X-ray test was a good and rapid predictor of seed
viability.
PMID- 28490954
TI - Pretarsus structure in relation to climbing ability in the ants Brachyponera
sennaarensis and Daceton armigerum.
AB - We studied the external and internal pretarsus structure of the ants Brachyponera
sennaarensis and Daceton armigerum in relation to their very different climbing
ability. B. sennaarensis is a ground-dwelling species that is not able to climb
vertical smooth walls. They have a pair of straight pretarsal claws with an
average claw tip angle of 56 degrees, while the ventral tarsal surface lacks fine
hairs that touch the substrate. They have no adhesive pad on the vestigial
arolium, while the arolium gland is very small. D. armigerum, on the other hand,
is an arboreal and thus well-climbing species with a very strong grip on the
substrate. Their pretarsal claws are very hooked, with a claw tip angle around 75
degrees. They have dense arrays of fine hairs on the ventral tarsal surface, a
well-developed arolium and arolium gland. These clearly different morphological
characteristics are in line with the opposite climbing performance of both
species.
PMID- 28490955
TI - Protection of oxidative stress induced apoptosis in osteosarcoma cells by
dihydromyricetin through down-regulation of caspase activation and up-regulation
of BcL-2.
AB - Current study was aimed to investigate the effect of dihydromyricetin on hydrogen
peroxide induced oxidative stress in the osteosarcoma cells. MTT assay showed
that hydrogen peroxide treatment at a concentration of 100 MUM caused a
significant (p < 0.005) reduction in the viability of MG63 cells. However,
reduction in cell viability caused by 100 MUM concentration of hydrogen peroxide
was completely prevented on incubation with 30 MUM dose of dihydromyricetin.
Treatment with 100 MUM concentration of hydrogen peroxide for 24 h led to
condensation of chromatin material, rounding of cell shape and detachment of
cells. The results from flow cytometry using annexin V-FITC and PI double
staining showed apoptosis induction in 47.84 +/- 5.21% cells on treatment with
100 MUM concentration of hydrogen peroxide compared to 2.32 +/- 0.54% in
controlcells. The apoptotic alterations in MG63 cell morphology were prevented
significantly on pre-treatment with 30 MUM doses of dihydromyricetin for 48 h.
Annexin V-FITC and PI staining showed reduction of hydrogen peroxide induced
apoptotic cell percentage to 3.07 +/- 0.86% on pre-treatment of MG63 cells with
30 MUM dose of dihydromyricetin. Western blot analysis showed a significant
increase in the activation of caspase-3 and -9 on treatment of MG63 cells for 24
h with 100 MUM concentration of hydrogen peroxide. The expression level of Bcl-2
was decreased significantly by 100 MUM concentration of hydrogen peroxide in MG63
cells. However, pre-treatment of MG63 cells with 30 MUM dose of dihydromyricetin
for 48 h significantly prevented hydrogen peroxide induced increase in caspase-3
and -9 levels and reduction in Bcl-2 level. Thus dihydromyricetin prevents
hydrogen peroxide induced reduction in viability and induction of apoptosis in
MG63 cells through down-regulation of caspase activation and up-regulation of Bcl
2 levels.
PMID- 28490956
TI - Changes in the NFkappaB and E-cadherin expression are associated to diabetic
nephropathy inPsammomys obesus.
AB - Diabetes mellitus is a major leading cause of end-stage renal failure,
characterized by kidney inflammation and glomerular dysfunction, in worldwide.
Kidney inflammation is associated to modifications in the expression levels of
pro-inflammatory molecules, such as nuclear factor-kappaB (NFkappaB) and adhesion
molecules, such as E-cadherin, leading to glomerular dysfunction. However, the
relationships between these two processes in human diabetic nephropathy remain an
open question. Since Psammomys obesus is an ideal animal model to study diabetes
mellitus temporal evolution, we have used this model to study the correlation
between kidney structural changes and modification on the expression levels of
NFkappaB and E-cadherin over time. We have demonstrated that, after induction of
diabetes metillus with a high energy diet (HED), P. obesus develops the
characteristic symptoms of human disease. In detail, at the third month nuclear
factor NFkappaB is expressed in the kidney of diabetic P. obesus and structural
renal changes, such as mesangial expansion or interstitial fibrosis, are
detectable; at 6 months, thickening of glomerular basement membrane, glomerular
sclerosis, and tubular atrophy occurs; at 9 months, symptoms of the final stages
of the disease, such as down expression of E-cadherin, happens. As a result of
these observations we proposed that NFkappaB activation and E-cadherin down
expression are interlinked on diabetic kidney disease (DKD).
PMID- 28490957
TI - Isolation of the symbiotic fungus of Acromyrmex pubescens and phylogeny of
Leucoagaricus gongylophorus from leaf-cutting ants.
AB - Leaf-cutting ants live in an obligate symbiosis with a Leucoagaricus species, a
basidiomycete that serves as a food source to the larvae and queen. The aim of
this work was to isolate, identify and complete the phylogenetic study of
Leucoagaricus gongylophorus species of Acromyrmex pubescens. Macroscopic and
microscopic features were used to identify the fungal symbiont of the ants. The
ITS1-5.8S-ITS2 region was used as molecular marker for the molecular
identification and to evaluate the phylogeny within the Leucoagaricus genus. One
fungal symbiont associated with A. pubescens was isolated and identified as L.
gongylophorus. The phylogeny of Leucoagaricus obtained using the ITS molecular
marker revealed three well established monophyletic groups. It was possible to
recognize one clade of Leucoagaricus associated with phylogenetically derived
leaf-cutting ants (Acromyrmex and Atta). A second clade of free living forms of
Leucoagaricus (non-cultivated), and a third clade of Leucoagaricus associated
with phylogenetically basal genera of ants were also recognized. The clades
corresponded to traditional taxonomic groups, and were differentiated by
ecological habitats of different species.
PMID- 28490958
TI - Transplantation of human neonatal foreskin stromal cells in ex vivo organotypic
cultures of embryonic chick femurs.
AB - We have previously reported that human neonatal foreskin stromal cells (hNSSCs)
promote angiogenesis in vitro and in chick embryo chorioallantoic membrane (CAM)
assay in vivo. To examine the in vivo relevance of this observation, we examined
in the present study the differentiation potential of hNSSCs in ex vivo
organotypic cultures of embryonic chick femurs. Isolated embryonic chick femurs
(E10 and E11) were cultured for 10 days together with micro-mass cell pellets of
hNSSCs, human umbilical vein endothelial cells (HUVEC) or a combination of the
two cell types. Changes in femurs gross morphology and integration of the cells
within the femurs were investigated using standard histology and
immunohistochemistry. After 10 days, the femurs that were cultured in the
presence of hNSSCs alone or hNSSC + HUVEC cells grew longer, exhibited thicker
diaphysis and an enlarged epiphyseal region compared to control femurs cultured
in the absence of cells. Analysis of cell-femur interactions, revealed intense
staining for CD31 and enhanced deposition of collagen rich matrix along the
periosteum in femurs cultured with hNSSCs alone or hNSSCs + HUVEC and the most
pronounced effects were observed in hNSSC + HUVEC cultures. Our data suggest that
organotypic cultures can be employed to test the differentiation potential of
stem cells and demonstrate the importance of stem cell interaction with 3D-intact
tissue microenvironment for their differentiation.
PMID- 28490959
TI - Physiological parameters correlated with Tomato Mosaic Virus inducing defensive
response in Datura metel.
AB - Programed cell death resembles a real nature active defense in Datura metel
against TMV after three days of virus infection. This adaptive plant immune
response was quantitatively assessed against Tomato Mosaic Virus infection by the
following physiological markers; Chlorophyll-a (mg/g), Chlorophyll-b (mg/g),
total protein (mg/g), hydrogen peroxide H2O2 (MUmol/100 mg), DNA (MUg/100 mg),
RNA (MUg/100 mg), Salicylic acid (MUg/g), and Comet Assays. Parameters were
assessed for asymptomatic healthy and symptomatic infected detached leaves. The
results indicated H2O2 and Chlorophyll-a as the most potential parameters.
Chlorophyll-a was considered the only significant predictor variant for the H2O2
dependent variant with a P value of 0.001 and R-square of 0.900. The plant immune
response was measured within three days of virus infection using the cutoff value
of H2O2 (?1.095 MUmol/100 mg) and (?3.201 units) for the tail moment in the Comet
Assay. Their percentage changes were 255.12% and 522.40% respectively which
reflects the stress of virus infection in the plant. Moreover, H2O2 showed 100%
specificity and sensitivity in the symptomatic infected group using the receiver
operating characteristic (ROC). All tested parameters in the symptomatic infected
group had significant correlations with twenty-five positive and thirty-one
negative correlations where the P value was <0.05 and 0.01. Chlorophyll-a
parameter had a crucial role of highly significant correlation between total
protein and salicylic acid. Contrarily, this correlation with tail moment unit
was (r = -0.930, P < 0.01) where the P value was <0.01. The strongest significant
negative correlation was between Chlorophyll-a and H2O2 at P < 0.01, while
moderate negative significant correlation was seen for Chlorophyll-b where the P
value < 0.05. The present study discloses the secret of the three days of rapid
transient production of activated oxygen species (AOS) that was enough for having
potential quantitative physiological parameters for defensive plant response
toward the virus.
PMID- 28490960
TI - Chemical composition, antibacterial and antifungal activities of flowerhead and
root essential oils of Santolina chamaecyparissus L., growing wild in Tunisia.
AB - The antimicrobial properties of essential oil from various Santolina species have
not been investigated enough in the previous studies dealing with the biological
activities of medicinal plants. In Tunisia, Santolina chamaecyparissus L.
(Asteraceae) is the only Santolina species recorded and is used as vermifuge and
emmenagogue. The chemical composition, antibacterial and antifungal properties of
essential oils from the flowerheads and roots of spontaneous S. chamaecyparissus
growing in Tunisia and the chemical composition which leads to the Tunisian
chemotype are investigated here for the first time. Essential oils isolated by
hydro distillation from flowerheads and roots of S. chamaecyparissus were
analyzed by GC and GC/MS. Two methods served for antimicrobial assays of the
essential oils: diffusion in a solid medium and micro-well dilution assay.
Antifungal tests were carried out by the agar incorporation method. Sixty-seven
constituents were identified from the essential oil of the flowerhead. The major
constituents were: 1,8-cineole and beta-eudesmol. Two non identified compounds
were present at the highest concentration in root oil. Flowerhead oil was
characterized by high contents in monoterpenes and sesquiterpenes oxygenated
compounds. The flowerhead essential oil demonstrated potent of antibacterial
properties against Pseudomonas aeruginosa ATCC and Enterococcus faecalis ATCC,
with MIC of 0.625 MUg/ml. These findings demonstrate that the flowerhead
essential oils of S. chamaecyparissus have excellent antibacterial properties and
for this reason they could contribute to decrease the problem of microbial
resistance to antibiotics.
PMID- 28490961
TI - Radiofrequency radiations induced genotoxic and carcinogenic effects on chickpea
(Cicer arietinum L.) root tip cells.
AB - Present study was under taken to predict the possible DNA damages (genotoxicity)
and carcinogenicity caused by radiofrequency radiations (RF) to living tissue.
Dry seeds of chickpea were treated with GSM cell phone (900 MHz) and laptop (3.31
GHz) as RF source for 24 and 48 h. Untreated seeds were used as (0 h) negative
control and Gamma rays (250 Gray) as positive control. Plant chromosomal
aberration assay was used as genotoxicity marker. All the treatment of RF
inhibits seed germination percentage. 48 h laptop treatment has the most negative
effect as compared to untreated control. A decrease was observed in mitotic index
(M.I) and increase in abnormality index (A.I) with the increase in exposure
duration and frequency in (Hz). Cell membrane damages were also observed only in
48 h exposure of cell phone and laptop (RF). Maximum nuclear membrane damages and
ghost cells were again recorded in 48 h exposure of cell phone and laptop. The
radiofrequency radiations (900 MHz and 3.31 GHz) are only genotoxic as they
induce micronuclei, bi-nuclei, multi-nuclei and scattered nuclei but could be
carcinogenic as 48 h incubation of RF induced fragmentation and ghost cells.
Therefore cell phones and laptop should not be used unnecessarily to avoid
possible genotoxic and carcinogenic effects.
PMID- 28490962
TI - Effects of perinatal exposure to Zamzam water on the teratological studies of the
mice offspring.
AB - Zamzam water is well documented for plenty of medicinal value for curing illness.
In the present study, the effects of perinatal consumption of Zamzam and normal
drinking water by the pregnant mice on their offspring's physical parameters,
early sensory motor reflexes, locomotor activities, acetylcholinesterase (AChE)
activity in the homogenize brain tissue and blood parameters were compared. To
achieve that; Zamzam water was given to female Swiss-Webster strain mice as the
only source of drinking fluid and the control animals were administered plain tap
water. Treatment started from the first day of pregnancy and continued until the
postnatal day fifteen of delivery. All offspring were subjected to various tests.
The rate of body weight gain remained relatively unaffected until the second week
of weaning period, however; in the last week the offspring exposed to Zamzam
water gained significant body weight as compared to their control offspring.
Furthermore, the opening of eyes and appearance of body hairs in Zamzam exposed
pups remained unaffected as compared to the controls. The sensory motor reflexes
in Zamzam exposed pups after birth and during the first two weeks of weaning
period were significantly increased. Locomotor Activity Test performed in the
male and female offspring after weaning period showed a significant decrease in
the male and increase in the female on most of the elements of this test due to
Zamzam exposure. AChE activity in the homogenized brain tissue and blood
parameters were unaffected as compared to the controls, the present Zamzam
effects in the offspring are possibly via in utero action and/or via mother's
milk.
PMID- 28490963
TI - Analysis of the bacterial strains using Biolog plates in the contaminated soil
from Riyadh community.
AB - Routine manufacture, detonation and disposal of explosives in land and
groundwater have resulted in complete pollution. Explosives are xenobiotic
compounds, being toxic to biological systems, and their recalcitrance leads to
persistence in the environment. The methods currently used for the remediation of
explosive contaminated sites are expensive and can result in the formation of
toxic products. The present study aimed to investigate the bacterial strains
using the Biolog plates in the soil from the Riyadh community. The microbial
strains were isolated using the spread plate technique and were identified using
the Biolog method. In this study we have analyzed from bacterial families of soil
samples, obtained from the different sites in 5 regions at Explosive Institute.
Our results conclude that Biolog MicroPlates were developed for the rapid
identification of bacterial isolates by sole-carbon source utilization and can be
used for the identification of bacteria. Out of five communities, only four
families of bacteria indicate that the microbial community lacks significant
diversity in region one from the Riyadh community in Saudi Arabia. More studies
are needed to be carried out in different regions to validate our results.
PMID- 28490964
TI - Effect of long-term exposure of mice to 900 MHz GSM radiation on experimental
cutaneous candidiasis.
AB - Mobile phones communicate with base stations using 900 MHz microwaves. The
current study was aimed to survey the effects of long-term 900 MHz microwave
exposure of mice on experimentally induced cutaneous candidiasis. Forty inbred,
male, BALB/c mice were randomly divided into four groups. Cutaneous lesions with
Candida albicans were experimentally induced on the lateral-back skin of the 20
mice. One group of the diseased mice were exposed (6 h per day and 7 d per week)
to 900 MHz microwave radiation, while the other groups were not exposed. Two
unexposed control groups were also included. The skin lesions were regularly
monitored and the live candida cell density was enumerated using the colony
forming unit (CFU) assay. The process was repeated after a one week resting
interval. One week later, all mice were challenged through intra tail veins using
LD90 dose of C. albicans. Mortality of the mice was recorded and the candida load
of the kidney homogenates from died animals was counted. 900 MHz microwave
exposed mice had 1.5 day and 3.7 day delays on wound healing in stages two. Live
Candida inoculated Wave exposed (LCW) mice also showed higher yeast loads in skin
lesions at days 5, 7 and 9 post inoculation. Survival analysis of live candida
challenged mice showed the radiation exposed group is prone to death induced by
systemic infection and candida enumeration from the kidney homogenates showed
radiation exposed animals have had significantly higher yeast load in the tissue.
In collection, long-term 900 MHz radiation exposure of mice led to longevity of
skin wounds and susceptibility of the animals to systemic challenge and higher
incidences of microorganisms in internal tissues.
PMID- 28490965
TI - Protective effects of fennel oil extract against sodium valproate-induced
hepatorenal damage in albino rats.
AB - Foeniculum vulgare (Apiaceae) is commonly known as fennel. This herb is well
known worldwide and traditionally used as curative herbal therapy for the
treatment of epileptic disease, seizurescarminative, digestive, lactogogue,
diuretic, treating respiratory and gastrointestinal disorders. The aim of present
study is to investigate the possible effect of fennel oil against the toxicity of
Sodium-Valproic (SVP) in albino rats. In order to assess the protection of fennel
oil on SVP induced hepato- and nephro-toxicity, male albino rats were treated
with 1 ml/kg b.w fennel oil 3 days/week for 6 weeks. The biochemical analyses of
hepatic enzymes were evaluated by estimating blood biomarkers of liver and renal
damage along with histological examination. The results obtained from this work
showed that treating animals with SVP lead to many histopathological alterations
in the liver and kidney tissues. The effect appeared in the liver tissue include
leukocyte infiltrations, cytoplasmic vacuolization of the hepatocytes, fatty
degeneration and congestion of blood vessels. This commonly used chemical (SVP)
caused some unwanted effects on the kidney cortex which histologically observed
as degeneration in renal tubules, atrophy of the glomeruli and edema. Biochemical
results also revealed an abnormal increase in the enzyme level of AST, SAT, ALP,
bilirubin, creatinine and urea-nitrogen, with a noticed decrease in total protein
content. However, the results of treated rats with SVP plus fennel oil showed
some positive histopathological changes in both the liver and kidney tissues.
These results have confirmed that fennel oil has positive effects on the
histological structure of the liver and kidney and the biochemical levels of AST,
ALT, ALP, bilirubin, total proteins, creatinine and urea. It is concluded that
fennel oil has various pharmacological properties including antioxidant, anti
cancer activity, anti-inflammatory. These valuable effects might be due to the
presence of aromatic compounds trans-anethole. This useful properties of fennel
plant could be due to its antioxidant activity that prevents the toxicity of SVP.
PMID- 28490966
TI - Survey of the reptilian fauna of the Kingdom of Saudi Arabia. VI. The snake fauna
of Turaif region.
AB - A collection of snakes in Turaif region, Kingdom of Saudi Arabia, an area that
has been poorly documented for reptiles, consists of 28 specimens representing 11
species belonging to 4 families (Colubridae, Elapidae, Viperidae and
Atractaspididae). This study presents the first comprehensive inventory of the
herpetofauna of the Turaif province of Saudi Arabia. Co-ordinates: Latitude,
longitude and altitude, of the collected specimens were mapped using GPS. Three
of the snake species Lytorhynchus diadema, Pseudocerastes fieldi and
Walterinnesia morgani reported by the authors in the present survey proved to be
new records for Turaif region of Saudi Arabia.
PMID- 28490967
TI - Comparative study of fatty-acid composition of table eggs from the Jeddah food
market and effect of value addition in omega-3 bio-fortified eggs.
AB - Health consciousness has increased the desire of people around the world to
consume functional foods. Omega-3 essential fatty acids are one among these
beneficial and important health supplements without which a general
predisposition to degenerative and stress related disorders can occur. Saudi
Arabia has shown an alarming increase in obesity (Al-Nozha et al., 2005),
diabetes (Alqurashi et al., 2011), and cardiovascular disease (Al-Nozha et al.,
2004) in the last few decades mainly due to nutritional transitions and lifestyle
alterations (Amuna and Zotor, 2008). Lack of nutrient dense foods and the
prevailing food related disorder of obesity (Popkin, 2001; Prentice, 2014)
especially render egg as a choice food to be value-added for attaining
nutritional security in Saudi Arabia and in effect reverse the increasing
incidences of lifestyle diseases. Nutritional intervention through a commonly
consumed food product would be an important step in improving the health of the
people, and reducing health care costs. As eggs are a frequently consumed food
item in Saudi Arabia, enriching them with omega-3 fatty acids would be an
excellent way to alleviate the existing problems. A significant deposition of
omega-3 fatty acids in the eggs was observed when the diet of hens was
supplemented with omega-3 fatty acids from either flaxseed or fish oil source.
Inadequacy of omega-3 fatty acids could thus be rectified by producing omega-3
enriched eggs from hens supplemented with flaxseed or fish oil source, and thus
contribute toward better health choice of the consumer.
PMID- 28490968
TI - Inhibitory activity of different medicinal extracts from Thuja leaves, ginger
roots, Harmal seeds and turmeric rhizomes against Fig leaf mottle-associated
virus 1 (FLMaV-1) infecting figs in Mecca region.
AB - Fig leaf mottle-associated virus-1 (FLMaV-1) is a closterovirus newly identified
in fig trees, in the Mecca region, suffering from mosaic disease symptoms and
apparently is compromising the fig plantation in the country. In the present
study, we demonstrated the efficiency of two in vivo experiments including pre
and post treatments using Thuja leaf, ginger roots, Harmal seeds and turmeric
rhizome extracts on symptoms expression of rooted cuttings infected with FLMaV-1-
and their impact on virus multiplication. Results showed that individual
treatments with ginger roots and turmeric rhizomes in pre-grafting experiments
and Thuja extract following Harmal seeds in post grafting experiments were
efficient against symptom development. In addition, results showed that the total
photosynthesis pigments; total soluble intracellular proteins and total phenol
contents were higher in infected treated cuttings compared with healthy ones,
thus it was taken as evidence on a mutual interaction between these extracts and
virus multiplication.
PMID- 28490969
TI - Differential expression of six genes and correlation with fatness traits in a
unique broiler population.
AB - Previous results from genome wide association studies (GWASs) in chickens
divergently selected for abdominal fat content of Northeast Agricultural
University (NEAUHLF) showed that many single nucleotide polymorphism (SNP)
variants were associated with abdominal fat content. Of them, six top significant
SNPs at the genome level were located within SRD5A3, SGCZ, DLC1, GBE1, GALNT9 and
DNAJB6 genes. Here, expression levels of these six candidate genes were
investigated in abdominal fat and liver tissue between fat and lean broilers from
the 14th generation population of NEAUHLF. The results showed that expression
levels of SRD5A3, SGCZ and DNAJB6 in the abdominal fat and SRD5A3, DLC1, GALNT9,
DNAJB6 and GBE1 in the liver tissue differed significantly between the fat and
lean birds, and were correlated with abdominal fat traits. The findings will
provide important references for further function investigation of the six
candidate genes involved in abdominal fat deposition in chickens.
PMID- 28490970
TI - Antibacterial activities of the methanol extracts of Albizia adianthifolia,
Alchornea laxiflora, Laportea ovalifolia and three other Cameroonian plants
against multi-drug resistant Gram-negative bacteria.
AB - In the last 10 years, resistance in Gram-negative bacteria has been increasing.
The present study was designed to evaluate the in vitro antibacterial activities
of the methanol extracts of six Cameroonian medicinal plants Albizia
adianthifolia, Alchornea laxiflora, Boerhavia diffusa, Combretum hispidum,
Laportea ovalifolia and Scoparia dulcis against a panel of 15 multidrug resistant
Gram-negative bacterial strains. The broth microdilution was used to determine
the minimal inhibitory concentration (MIC) and minimal bactericidal concentration
(MBC) of the extracts. The preliminary phytochemical screening of the extracts
was conducted according to the reference qualitative phytochemical methods.
Results showed that all extracts contained compounds belonging to the classes of
polyphenols and triterpenes, other classes of chemicals being selectively
distributed. The best antibacterial activities were recorded with bark and root
extracts of A. adianthifolia as well as with L. ovalifolia extract, with MIC
values ranging from 64 to 1024 MUg/mL on 93.3% of the fifteen tested bacteria.
The lowest MIC value of 64 MUg/mL was recorded with A. laxiflora bark extract
against Enterobacter aerogenes EA289. Finally, the results of this study provide
evidence of the antibacterial activity of the tested plants and suggest their
possible use in the control of multidrug resistant phenotypes.
PMID- 28490972
TI - Intensifying responsiveness towards neglected intestinal helminth infections in a
resource-constrained setting.
AB - Neglected intestinal helminth infections afflict the marginalized communities in
Asia. Since 2004, growing body of evidence in Myanmar indicated high prevalence
of soil-transmitted helminths (STH) infections (30-40%) among school children. Co
existence of STH (23%) with food-borne trematodes was noted among 383 pregnant
women in a selected township in 2012-2014 followed by molecular verification of
very low prevalence of schistosome infection (<5%) in the same study site in
2016. The success of transmission elimination plans may depend upon sensitive
diagnostic tools to detect persistent infections and polyparasitism. Addressing
the research gaps in vulnerable sites requires an increased investment in
resource-constrained settings.
PMID- 28490971
TI - Chemoprotective effect of omega-3 fatty acids on thioacetamide induced hepatic
fibrosis in male rats.
AB - The current study was designed to investigate the possible protective effect of
omega-3 fatty acids from fish oil on hepatic fibrosis induced by thioacetamide
(TAA) in male rats. The experimental animals were divided into four groups. The
first group was received saline solution and served as control. The second group
was given 250 mg/kg body weight of TAA. The third group was treated with omega-3
fatty acids and TAA. The fourth group was given saline solution and supplemented
with omega-3 fatty acids. Treatment of rats with TAA for three and six weeks
resulted in a significant decrease in body weight gain, while the value of
liver/body weight ratio was statistically increased. Furthermore, the levels of
serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase,
gamma glutamyl transferase and total bilirubin were significantly increased.
After three weeks of exposure to only TAA, liver sections showed an abnormal
morphology characterized by noticeable fibrosis with the extracellular matrix
collagen contents and damage of liver cells' structure. Liver sections from rats
treated with only TAA for six weeks revealed an obvious increase in extracellular
matrix collagen content and bridging fibrosis. Treating TAA-intoxicated rats with
omega-3 fatty acids significantly attenuated the severe physiological and
histopathological changes. Finally, the present investigation suggests that omega
3 fatty acids could act against hepatic fibrosis induced by TAA due to its
antioxidant properties, thus supporting its use in hepatic fibrosis therapy.
PMID- 28490973
TI - Transnational organizing: Issue professionals in environmental sustainability
networks.
AB - An ongoing question for institutional theory is how organizing occurs
transnationally, where institution building occurs in a highly ambiguous
environment. This article suggests that at the core of transnational organizing
is competition and coordination within professional and organizational networks
over who controls issues. Transnational issues are commonly organized through
professional battles over how issues are treated and what tasks are involved.
These professional struggles are often more important than what organization has
a formal mandate over an issue. We highlight how 'issue professionals' operate in
two-level professional and organizational networks to control issues. This two
level network provides the context for action in which professionals do their
institutional work. The two-level network carries information about professional
incentives and also norms about how issues should be treated and governed by
organizations. Using network and career sequences methods, we provide a case of
transnational organizing through professionals who attempt issue control and
network management on transnational environmental sustainability certification.
The article questions how transnational organizing happens, and how we can best
identify attempts at issue control.
PMID- 28490974
TI - The introduction of biosimilars of low molecular weight heparins in Europe: a
critical review and reappraisal endorsed by the Italian Society for Haemostasis
and Thrombosis (SISET) and the Italian Society for Angiology and Vascular
Medicine (SIAPAV).
AB - Recently, the European Medicines Agency (EMA) authorized the introduction and
marketing of Thorinane(r) and Inhixa(r), biosimilars of the Low Molecular Weight
Heparin (LMWH) enoxaparin. The authorization path is considerably different from
the guidelines published by the EMA in 2009, as well as from the recommendations
from the International Society on Thrombosis and Haemostasis published in 2013.
Indeed, both of them recommended that LMWHs biosimilars therapeutic equivalence
should be demonstrated in at least one adequately designed clinical trial.
Shortly after enoxaparin biosimilars approval, EMA published a revised version of
its guideline, no longer requiring the execution of a clinical study in patients
at risk of venous thromboembolism. Also the assessment of safety shows some
relevant flaws, as it relies only on a 20 healthy volunteers study, clearly
underpowered to draw any conclusions about the safety profile of the drug. In our
opinion, the approach taken by EMA for approval of enoxaparin biosimilars raises
serious concerns about their actual, clinical "similarity". On these grounds,
with the endorsement of the Italian Society for Haemostasis and Thrombosis
(SISET) and the Italian Society for Angiology and Vascular Medicine (SIAPAV), we
elaborated the present document aimed at reviewing and reappraising some critical
points regarding the introduction of biosimilars of LMWH in Europe. Moreover, we
would strongly advise the Italian National Health Authorities not to entrust
safety assessment to the post-marketing surveillance only, but to promote well
designed and powered studies aimed at establish the actual efficacy and safety of
LMWH biosimilars.
PMID- 28490975
TI - Comparison of transepithelial resistance measurement techniques: Chopsticks vs.
Endohm.
AB - BACKGROUND: TER measurements across confluent cellular monolayers provide a
useful indication of TJ strength between epithelial and endothelial cells in
culture. Having a reliable and accurate method of measuring cell-to-cell adhesion
is critical to studies in pathophysiology and cancer metastasis. However, the use
of different technical approaches to measure TER has reportedly yielded
inconsistent measurements within the same cell lines. METHODS: In the current
study, we compared the peak TER values for the MDCK (canine kidney) and MCF-7
(human breast cancer) epithelial cell lines using two common approaches
(Chopstick and Endohm) and two types of polymer inserts (PC and PET). RESULTS:
Both cell lines demonstrated a statistically significant difference in the peak
TERs obtained using the two different approaches. Further, the MDCK (but not the
MCF-7) cells demonstrated a statistically significant difference between the peak
TERs when using the same approach but different inserts. CONCLUSION: Our study
indicates the importance of using a single approach when seeking to measure and
compare the TER values of cultured cell lines.
PMID- 28490976
TI - Teaching Stimulus-Stimulus Relations to Minimally Verbal Individuals: Reflections
on Technology and Future Directions.
AB - This paper discusses recent methodological approaches and investigations that are
aimed at developing reliable behavioral technology for teaching stimulus-stimulus
relations to individuals who are minimally verbal and show protracted difficulty
in acquiring such relations. The paper has both empirical and theoretical
content. The empirical component presents recent data concerning the possibility
of generating rapid relational learning in individuals who do not initially show
it. The theoretical component (1) considers decades of methodological
investigations with this population and (2) suggests a testable hypothesis
concerning some individuals exhibit unusual difficulties in learning. Given this
background, we suggest a way forward to better understand and perhaps resolve
these learning challenges.
PMID- 28490977
TI - Editorial.
PMID- 28490978
TI - Radiobiology of stereotactic body radiation therapy (SBRT).
AB - Recent advances in the technology of radiotherapy have enabled the development of
new therapeutic modalities that deliver radiation with very high accuracy,
reduced margins and high dose conformation, allowing the reduction of healthy
tissue irradiated and therefore minimizing the risk of toxicity. The next step
was to increase the total tumor dose using conventional fractionation (which
remains the best way to relatively radioprotect healthy tissues when large
volumes are treated) or to use new fractionation schemes with greater biological
effectiveness. Based on the experience gained in radiosurgery, the latter way was
chosen for small and well-defined tumors in the body. Stereotactic body
radiotherapy delivers high doses of radiation to small and well-defined targets
in an extreme hypofractionated (and accelerated) scheme with a very high
biological effectiveness obtaining very good initial clinical results in terms of
local tumor control and acceptable rate of late complications. In fact, we
realize a posteriori that it was not feasible to administer such biologically
equivalent dose in a conventional fractionation because the treatment could last
several months. So far, these new therapeutic modalities have been developed due
to technologic advances in image guidance and treatment delivery but without a
solid biological basis. It is the role of traditional radiobiology (and molecular
radiobiology) to explain the effects of high doses of ionizing radiation on tumor
and normal tissues. Only through a better understanding of how high doses of
ionizing radiation act, clinicians will know exactly what we do, allowing us in
the future to refine our treatments. This article attempts to describe through
simple and understandable concepts the known aspects of the biological action of
high doses of radiation on tumor and normal tissues, but it is clear that we need
much more basic research to better understand the biology of high doses of
radiation.
PMID- 28490979
TI - Dose to organ at risk and dose prescription in liver SBRT.
AB - Stereotactic body radiation therapy (SBRT) is delivered in a curative intent to
many primary and secondary tumors. Concerning liver metastasis, SBRT can be
safely delivered using one to five fractions. An excellent local control is
obtained with doses from 20 to 60 Gy. For primary hepatic tumors, results are
also good, but the risk of hepatic toxicity related to liver pre-existent
pathology must be taken into account. Radiation induced liver disease (RILD) is
not frequent in its classical presentation, but modifications of liver enzymes
are often observed. Other toxicities of SBRT on the duodenum, small bowel and
biliary tract are also described. With respect to contraindications and dose
limitations on surrounding structures, SBRT is well tolerated and takes place
among curative treatment of liver tumors, as surgery, radiofrequency and
embolization.
PMID- 28490980
TI - SBRT planning for liver metastases: A focus on immobilization, motion management
and planning imaging techniques.
AB - AIM: To evaluate the different techniques used for liver metastases Stereotactic
Body Radiation Therapy (SBRT) planning. We especially focused on immobilization
devices, motion management and imaging used for contouring. BACKGROUND: Although
some guidelines exist, there is no consensus regarding the minimal requirements
for liver SBRT treatments. MATERIALS AND METHODS: We reviewed the main liver
metastases SBRT publications and guidelines; and compared the techniques used for
immobilization, motion management, margins and imaging. RESULTS: There is a wide
variety of techniques used for immobilization, motion management and planning
imaging. CONCLUSIONS: We provide a subjective critical analysis of minimal
requirements and ideal technique for liver SBRT planning.
PMID- 28490981
TI - Robotic radiosurgery for the treatment of liver metastases.
AB - AIM: This study evaluates the toxicity and outcome in patients treated with
robotic radiosurgery for liver metastases. BACKGROUND: Modern technologies allow
the delivery of high doses to the liver metastases while lowering the dose to the
neighboring organs at risk. Whether this dosimetric advantage translates into
clinical benefit is not well known yet. METHODS AND MATERIALS: A total of 9
patients with 17 liver metastases have been treated with robotic stereotactic
body radiotherapy SBRT from March 2011 to December 2014. Local response to SBRT
was graded by the Response Evaluation Criteria in Solid Tumors criteria to
describe change in treated tumor lesion. Adverse events after SBRT were graded on
a 1-5 scale according to the National Cancer Institute common terminology
criteria for adverse events v4.0. RESULTS: Patients received either three (78%)
or five (22%) fractions. Patients were treated with a mean fraction dose of 14 Gy
with a range from 9 to 20 Gy. The median total radiation dose provided to
patients was 45 Gy with a range of 45-60 Gy. Four out of the 17 (23.5%) treated
lesions had a complete response, 9 (53%) partial response and 3 (17.6%) stable
disease. With a median follow-up of 15.2 months after SBRT treatment, local
control and overall survival rated were 89% and 66%, respectively. No patient
experienced grade >=3 toxicity. The most common toxicity reported was asthenia.
Only two patients had nausea and diarrhea, 10 and 14 days after SBRT,
respectively. CONCLUSIONS: Robotic radiosurgery is a safe and effective local
treatment option for secondary liver tumors. Further prospective studies are
ongoing to determine long-term response and survival after robotic-SBRT for liver
metastases.
PMID- 28490982
TI - Radiosurgery for liver metastases. A single institution experience.
AB - AIM: To report our initial results on the use of radiosurgery for treatment of
liver metastases. BACKGROUND: In recent years there has been increasing interest
in the use of stereotactic body radiation therapy to treat metastatic disease to
the liver as an alternative to interventional procedures. MATERIALS AND METHODS:
Between November 2008 and June 2015 a total of 36 LINAC-based radiosurgeries
using VMAT were performed in 27 patients with liver metastases from 10 different
primary sites. Doses ranged from 21 Gy to 60 Gy in 1 to 5 fractions. In all
patients the volume of liver receiving less than 15 Gy was more than 700 cc. The
volume treated with the prescription dose ranged from 1 cc to 407 cc with a
median of 58 cc. All patients but one received systemic treatment. RESULTS:
Overall median survival for the entire group is 9 months (ranging from 1 to 67
months). Local recurrence free survival ranged from 4 to 67 months with a median
of 14 months. Twenty patients (80%) survived more than six months. Three patients
treated for oligometastases were alive after 3 years. Grade 0 toxicity was
encountered in 22/27 patients, Grade 1 toxicity in 5/27 and only 1/27 patient
experienced Grade 2 toxicity. No patient experienced grade 3-4 toxicity.
CONCLUSION: Based on these initial results we conclude that SBRT for treating
liver metastases with radiosurgery is safe and effective for treating one or
multiple lesions as long as normal tissue constraints for liver are respected.
PMID- 28490983
TI - Institutional experience in the treatment of colorectal liver metastases with
stereotactic body radiation therapy.
AB - AIM: To investigate whether the impact of dose escalation in our patient
population represented an improvement in local control without increasing
treatment related toxicity. MATERIALS AND METHODS: A cohort of consecutive
patients with colorectal liver metastases treated with stereotactic body
radiation therapy (SBRT) between December 2002 and December 2013 were eligible
for this study. Inclusion criteria were a Karnofsky performance status >=80% and,
according to the multidisciplinary tumor board, ineligibility for surgery or
radiofrequency ablation. Exclusion criteria were a lesion size >6 cm, more than 3
metastases, and treatment delivered with other fractionation scheme than 3 times
12.5 Gy or 16.75 Gy prescribed at the 65-67% isodose. To analyze local control,
CT or MRI scans were acquired during follow-up. Toxicity was scored using the
Common Toxicity Criteria Adverse Events v4.0. RESULTS: A total of 40 patients
with 55 colorectal liver metastases were included in this study. We delivered
37.5 Gy to 32 lesions, and 50.25 Gy to 23 lesions. Median follow-up was 26 and 25
months for these two groups. Local control at 2 and 3 years was 74 and 66% in the
low dose group while 90 and 81% was reached in the high dose group. No
significant difference in local control between the two dose fractionation
schemes could be found. Grade 3 toxicity was limited and was not increased in the
high dose group. CONCLUSIONS: SBRT for colorectal liver metastases offers a high
chance of local control at long term. High irradiation doses may contribute to
enhance this effect without increasing toxicity.
PMID- 28490984
TI - Evaluation of reproducibility of tumor repositioning during multiple breathing
cycles for liver stereotactic body radiotherapy treatment.
AB - AIM: To evaluate the tumor repositioning during gated volumetric modulated arc
therapy (VMAT) for liver stereotactic body radiotherapy(SBRT) treatment using
implanted fiducial markers and intrafraction kilovoltage (kV) images acquired
during dose delivery. MATERIALS AND METHODS: Since 2012, 47 liver cancer patients
with implanted fiducial markers were treated using the gated VMAT technique with
a Varian Truebeam STx linear accelerator. The fiducial markers were implanted
inside or close to the tumor target before treatment simulation. They were
defined at the maximum inhalation and exhalation phases on a 4-dimensionnal
computed tomography (4DCT) acquisition. During the treatment, kV images were
acquired just before the beam-on at each breathing cycle at maximum exhalation
and inhalation phases to verify the fiducial markers positions. For the five
first fractions of treatment in the first ten consecutive patients, a total of
2705 intrafraction kV images were retrospectively analyzed to assess the
differences between expected and actual positions of the fiducial markers along
the cranio-caudal (CC) direction during the exhalation phase. RESULTS: The mean
absolute intrafractional fiducial marker deviation along the CC direction was 1.0
mm at the maximum exhalation phase. In 99%, 95% and 90% cases, the fiducial
marker deviations were <=4.5 mm, 2.8 mm and 2.2 mm, respectively. CONCLUSION:
Intrafraction kV images allowed us to ensure the consistency of tumor
repositioning during treatment. In 99% cases, the fiducial marker deviations were
<=4.5 mm corresponding to our 5 mm treatment margin. This margin seems to be well
adapted to the gated VMAT SBRT treatment in liver disease.
PMID- 28490985
TI - Imaged-guided liver stereotactic body radiotherapy using VMAT and real-time
adaptive tumor gating. Concerns about technique and preliminary clinical results.
AB - BACKGROUND: Motion management is a major challenge in abdominal SBRT. We present
our study of SBRT for liver tumors using intrafraction motion review (IMR)
allowing simultaneous KV information and MV delivery to synchronize the beam
during gated RapidArc treatment. MATERIALS AND METHODS: Between May 2012 and
March 2015, 41 patients were treated by liver SBRT using gated RapidArc technique
in a Varian Novalis Truebeam STx linear accelerator. PTV was created by expanding
5 mm from the ITV. Dose prescription ranged from 40 to 50 Gy in 5-10 fractions.
The prescribed dose and fractionation were chosen depending on hepatic function
and dosimetric results. Thirty-four patients with a minimal follow-up of six
months were analyzed for local control and toxicity. Accuracy for tumor
repositioning was evaluated for the first ten patients. RESULTS: With a median
follow-up of 13 months, the treatment was well tolerated and no patient presented
RILD, perforation or gastrointestinal bleeding. Acute toxicity was found in 3
patients with G1 abdominal pain, 2 with G1 nausea, 10 with G1 asthenia and 1 with
G2 asthenia. 6 patients presented asymptomatic transitory perturbation of liver
enzymes. In-field local control was 90.3% with 7 complete responses, 14 partial
responses and 7 stabilisations. 3 patients evolved "in field". 12 patients had an
intrahepatic progression "out of field". Mean intrafraction deviation of
fiducials in the craneo-caudal direction was 0.91 mm (0-6 mm). CONCLUSION: The
clinical tolerance and oncological outcomes were favorable when using image
guided liver SBRT with real-time adaptive tumor gating.
PMID- 28490986
TI - Image guided SBRT for multiple liver metastases with ExacTrac(r) Adaptive Gating.
AB - AIM: To report the outcome and toxicity of sequential stereotactic body
radiotherapy (SBRT) for multiple liver metastases in patients treated with
ExacTrac Adaptive Gating. BACKGROUND: In selected patients with a limited number
of liver metastases, SBRT has been evaluated as a safe and effective treatment,
with minimal toxicity and high rates of local control. MATERIALS AND METHODS:
From April 2008 to October 2013, 21 patients with multiple (3-14) liver
metastases (n = 101) were treated sequentially with SBRT at our institution.
Maximum tumor diameter was 7.5 cm. Prior to treatment, internal markers were
placed inside or near the tumor. CT or PET-CT simulation was used for the
definition of gross tumor volume (GTV). Median planning target volume was 32.3 cc
(3.6-139.3 cc). Treatment consisted of 3 fractions (12-20 Gy/fraction) or 5
fractions (10 Gy/fraction), prescribed to the 90-95% of the PTV volume. Daily
intra-fraction image guidance was performed with ExacTrac Adaptive Gating.
Regular follow-up included CT or PET-CT imaging. RESULTS: After a median of 23.2
months, the estimated local control rate was 94.4%, 80.6%, 65% and 65% after 1,
2, 3 and 4 years; the median overall survival was 62 months (95% CI 49.12-74.87)
and the actuarial survival reached at 60 months was 57.6%. The univariate data
analysis revealed that only primary histology other than colorectal
adenocarcinoma was shown as an independent significant prognostic factor for
local control (p = 0.022). Number of treated metastases did not modify
significantly the overall survival (p = 0.51). No toxicity higher than G3 (1
patient with chest wall pain) and no radiation-induced liver disease were
observed. CONCLUSIONS: Sequential SBRT with ExacTrac Adaptive Gating for multiple
liver metastases can be considered an effective, safe therapeutic option, with a
low treatment-related toxicity. Excellent rates of local control and survival
were obtained.
PMID- 28490987
TI - Stereotactic body radiation therapy for liver metastasis - The linac-based
Greater Poland Cancer Centre practice.
AB - AIM: The main purpose of this work is to give a technical description and present
the properties of the liver SBRT protocol implemented in the Greater Poland
Cancer Centre (GPCC) in Poznan, Poland. BACKGROUND: Stereotactic body radiation
therapy (SBRT) for liver metastasis is a non-invasive therapeutic option which
enables irradiation of a small target in the body with a high dose. MATERIALS AND
METHODS: This study presents details of our linac-based liver SBRT protocol.
Special emphasis has been placed on fiducial implantation, patient preparation
(CT scanning, immobilization), treatment planning, and its implementation.
RESULTS: The liver SBRT treatment course implemented in the GPCC consists of
three fractions to deliver a total of 45 Gy. Fraction delivery details with
description of patient positioning (localization of liver metastasis) are
presented below. CONCLUSIONS: The literature validation of the assumptions
concerning the steps of the GPCC linac-based liver SBRT procedure show their
potential for an effective and patient friendly implementation.
PMID- 28490988
TI - The role of SBRT in oligometastatic patients with liver metastases from breast
cancer.
AB - Liver metastases from breast cancer are a common occurrence. Local ablative
therapies are a promising therapeutic option for these patients, with the
potential for a long term disease control in the setting of "oligometastatic
patients". Identification of the perfect candidate for local approaches is still
challenging and unclear. Stereotactic body radiation therapy (SBRT) is one of the
most valuable local therapy, because of great efficiency, low morbidity and
minimal invasiveness. In this paper, we reviewed the state of the art in the care
of breast cancer patients with liver metastases, with a focus on SBRT.
PMID- 28490989
TI - Evaluation of response after SBRT for liver tumors.
AB - Stereotactic body radiotherapy (SBRT) has developed over the last few years for
the treatment of primary and metastatic hepatic tumors. The tumoral and adjacent
peritumoral modifications caused by this radiosurgery limit the evaluation of
response by anatomic imaging and dimensional criteria alone, such as with RECIST.
This suggests that it is of interest to also take into account the residual
enhancement and hyper metabolism of these hepatic targets. We have reviewed the
English language literature regarding the response of hepatic lesions treated by
SBRT, and found that only seven articles were specifically concerned with this
problem. The response of the hepatocellular carcinoma after SBRT has been studied
specifically with multiphase enhanced CT-scan. Criteria set by the European
Association of Study of the Liver better estimate response at each time point of
follow up than RECIST does. Non-enhancement, reflecting tumor necrosis, is
additionally an early indicator of response with extended response in time and a
best non-enhancement percentage is observed at 12 months. The response after
treatment by SBRT of cholangiocarcinoma has not yet generated a specific report.
Use of RECIST criteria is also inadequate in the evaluation of response after
SBRT for hepatic metastases. Response of liver metastases to SBRT is better
assessed with a combination of size and enhancement pattern. The occurrence of a
lobulated enhancement during follow up is efficient to predict local progression
in a specific, reproducible, and sensitive way. Patients with FDG-avid hepatic
metastases are also better evaluated with PET-CT and functional criteria than
routine imaging and metric evaluation alone.
PMID- 28490990
TI - Management of liver cancer. The Surgeon's point of view.
AB - During the last twenty years, a huge progress has been achieved in the treatment
of liver cancer and recent strategies include interventional radiology,
chemotherapy regimens and surgery. Meanwhile, Stereotactic Body Radiation Therapy
(SRBT) has developed in the treatment of all organs with millimetre accuracy,
very few side effects and a high control rate. So, SRBT has become a therapeutic
weapon in his own right in liver tumour treatment. Many publications have
reported encouraging results in colorectal liver metastasis, hepatocellular
carcinoma on cirrhosis and peripheric cholangiocarcinoma. It is important that
radiation therapists involve systematic multidisciplinary "liver tumour" meetings
to discuss therapeutic indications and initiate treatments quickly.
PMID- 28490991
TI - Other non-surgical treatments for liver cancer.
AB - Interventional radiology plays a major role in the modern management of liver
cancers, in primary hepatic malignancies or metastases and in palliative or
curative situations. Radiological treatments are divided in two categories based
on their approach: endovascular treatment and direct transcapsular access.
Endovascular treatments include mainly three applications: transarterial
chemoembolization (TACE), transarterial radioembolization (TARE) and portal vein
embolization (PVE). TACE and TARE share an endovascular arterial approach,
consisting of a selective catheterization of the hepatic artery or its branches.
Subsequently, either a chemotherapy (TACE) or radioembolic (TARE) agent is
injected in the target vessel to act on the tumor. PVE raises the volume of the
future liver remnant in extended hepatectomy by embolizing a portal vein
territory which results in hepatic regeneration. Direct transcapsular access
treatments involve mainly three techniques: radiofrequency thermal ablation
(RFA), microwave thermal ablation (MWA) and percutaneous ethanol injection (PEI).
RFA and MWA procedures are almost identical, their clinical applications are
similar. A probe is deployed directly into the tumor to generate heat and
coagulation necrosis. PEI has known implications based on the chemical toxicity
of intra-tumoral injection with highly concentrated alcohol by a thin needle.
PMID- 28490992
TI - The Contribution of Cognitive Networks to Depression in Epilepsy.
AB - This review poses the question: Does disruption to cognitive brain networks in
epilepsy contribute to the problem of comorbid depression? Initial evidence
suggests that the network disease that gives rise to seizures has a predilection
for the same cognition-related networks that regulate mood, with comorbidity
reflective of more extensive disease. Framing both epilepsy and its psychiatric
comorbidities in terms of dysfunction in overlapping (cognitive) networks raises
the possibility that depression can be a primary feature of the disease in some
cases and facilitates an epilepsy classification system where behavioral features
of the disorder are embedded in a neurobiological mechanism.
PMID- 28490993
TI - An mTOuR of Epilepsy in Tuberous Sclerosis Complex.
PMID- 28490994
TI - Magnetoencephalography and Stereo-EEG Unite!
PMID- 28490995
TI - The Malrotated Hippocampal Formation: How Often Must We Judge Function by Shape?
PMID- 28490996
TI - Cannabidiol in Patients With Intractable Epilepsy Due to TSC: A Possible
Medication But Not a Miracle.
PMID- 28490997
TI - ADHD in Pediatric Epilepsy: Fact or Fiction?
PMID- 28490998
TI - Do Patients With Temporal Lobe Epilepsy and Cognitive Decline Have Alzheimer's
Disease or Chronic Traumatic Encephalopathy (CTE)?
PMID- 28490999
TI - Levetiracetam in Men With Epilepsy: Testosterone Is Left Alone But Sperm Count Is
Paramount.
PMID- 28491000
TI - Delayed Seizures and Poor Functional Outcome After Intracranial Hemorrhage Is the
Fate of Patients with a Poor Underlying Substrate, Say the Intensivists.
PMID- 28491001
TI - AED Switching: A Game of Skill or a Game of Chance?
PMID- 28491002
TI - Push and Pull: Borrowing Concepts From Control Theory for Seizure Spread.
PMID- 28491003
TI - Theta Rhythmopathy as a Cause of Cognitive Disability in TLE.
AB - Memory difficulties are commonly associated with temporal lobe epilepsy (TLE) and
cause significant disability. This article reviews the role of altered
hippocampal theta oscillations and theta-gamma coupling as potential causes of
memory disturbance in temporal lobe epilepsy, dissecting the potential mechanisms
underlying these changes in large-scale neuronal synchronization. We discuss
development of treatments for cognitive dysfunction directed at restoring theta
rhythmicity and future directions for research.
PMID- 28491004
TI - Precision Medicine: NMDA Receptor-Targeted Therapy for GRIN2D Encephalopathy.
PMID- 28491005
TI - Puritan's View of the "Menage a Trois".
PMID- 28491006
TI - Glycolysis Inhibition: The Gift of GAB(A).
PMID- 28491007
TI - Targeting Newly Generated Granule Cells: A Double-Edged Sword.
PMID- 28491008
TI - Decision Support System Requirements Definition for Human Extravehicular Activity
Based on Cognitive Work Analysis.
AB - The design and adoption of decision support systems within complex work domains
is a challenge for cognitive systems engineering (CSE) practitioners,
particularly at the onset of project development. This article presents an
example of applying CSE techniques to derive design requirements compatible with
traditional systems engineering to guide decision support system development.
Specifically, it demonstrates the requirements derivation process based on
cognitive work analysis for a subset of human spaceflight operations known as
extravehicular activity. The results are presented in two phases. First, a work
domain analysis revealed a comprehensive set of work functions and constraints
that exist in the extravehicular activity work domain. Second, a control task
analysis was performed on a subset of the work functions identified by the work
domain analysis to articulate the translation of subject matter states of
knowledge to high-level decision support system requirements. This work
emphasizes an incremental requirements specification process as a critical
component of CSE analyses to better situate CSE perspectives within the early
phases of traditional systems engineering design.
PMID- 28491009
TI - Simplified Approach Charts Improve Data Retrieval Performance.
AB - The effectiveness of different instrument approach charts to deliver minimum
visibility and altitude information during airport equipment outages was
investigated. Eighteen pilots flew simulated instrument approaches in three
conditions: (a) normal operations using a standard approach chart (standard
normal), (b) equipment outage conditions using a standard approach chart
(standard-outage), and (c) equipment outage conditions using a prototype
decluttered approach chart (prototype-outage). Errors and retrieval times in
identifying minimum altitudes and visibilities were measured. The standard-outage
condition produced significantly more errors and longer retrieval times versus
the standard-normal condition. The prototype-outage condition had significantly
fewer errors and shorter retrieval times than did the standard-outage condition.
The prototype-outage condition produced significantly fewer errors but similar
retrieval times when compared with the standard-normal condition. Thus, changing
the presentation of minima may reduce risk and increase safety in instrument
approaches, specifically with airport equipment outages.
PMID- 28491010
TI - Integrating Multidisciplinary Results to Produce New Knowledge About the
Physician-Patient Relationship: A Methodology Applied to the INTERMEDE Project.
AB - The INTERMEDE Project brought together a number of research teams to study the
interaction between a patient and their general practitioner, and how this can
produce social inequalities in health. The ultimate objective of the project was
to formalize a core of common findings by integrating qualitative and
quantitative results. The methodology chosen for the integration was inspired by
the Delphi participatory method. It involves several rounds of questions and
feedback in writing between all members of project teams, in order to compare
contradictory opinions and identify key concepts arising from the project. This
interdisciplinary research has provided a more nuanced understanding of the
mechanisms underlying physician-patient interaction by revealing the convergences
of the various disciplinary approaches.
PMID- 28491011
TI - An integrated proteomic and glycoproteomic approach uncovers differences in
glycosylation occupancy from benign and malignant epithelial ovarian tumors.
AB - BACKGROUND: Epithelial ovarian carcinomas encompass a heterogeneous group of
diseases with a poor 5-year survival rate. Serous carcinoma is the most common
type. Most FDA-approved serum tumor markers are glycoproteins. These
glycoproteins on cell surface or shed into the bloodstream could serve as
therapeutic targets as well as surrogates of tumor. In addition to glycoprotein
expressions, the analysis of protein glycosylation occupancy could be important
for the understanding of cancer biology as well as the identification of
potential glycoprotein changes in cancer. In this study, we used an integrated
proteomics and glycoproteomics approach to analyze global glycoprotein abundance
and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma
(HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC
MS/MS-based technique. METHODS: Fresh-frozen ovarian HGSC tissues and benign
serous cystadenoma cases were quantitatively analyzed using isobaric tags for
relative and absolute quantitation for both global and glycoproteomic analyses by
two dimensional fractionation followed by LC-MS/MS analysis using a Orbitrap
Velos mass spectrometer. RESULTS: Proteins and N-linked glycosite-containing
peptides were identified and quantified using the integrated global proteomic and
glycoproteomic approach. Among the identified N-linked glycosite-containing
peptides, the relative abundances of glycosite-containing peptide and the
glycoprotein levels were compared using glycoproteomic and proteomic data. The
glycosite-containing peptides with unique changes in glycosylation occupancies
rather than the protein expression levels were identified. CONCLUSION: In this
study, we presented an integrated proteomics and glycoproteomics approach to
identify changes of glycoproteins in protein expression and glycosylation
occupancy in HGSC and serous cystadenoma and determined the changes of
glycosylation occupancy that are associated with malignant and benign tumor
tissues. Specific changes in glycoprotein expression or glycosylation occupancy
have the potential to be used in the discrimination between benign and malignant
epithelial ovarian tumors and to improve our understanding of ovarian cancer
biology.
PMID- 28491012
TI - Are Alpha-2D Adrenoceptor Subtypes Involved in Rat Mydriasis Evoked by New
Imidazoline Derivatives: Marsanidine and 7-Methylmarsanidine?
AB - The imidazoline compounds may produce mydriasis after systemic administration to
some species (rats, cats, and mice). In mydriatic activity of imidazolines,
alpha2D-adrenoceptors subtype(s) seems to be involved. In this study, the pupil
dilatory effect evoked by 2 newly synthesized imidazoline derivatives-alpha2
adrenoceptor agonists: marsanidine and 7-methylmarsanidine-was compared. The
compounds were tested alone as well as in the presence of alpha2-adrenoceptor
antagonists (nonselective, yohimbine, and selective toward the following alpha2
adrenoceptor subtypes-alpha2A-2-[(4,5-dihydro-1H-imidazol-2-yl)methyl]-2,3
dihydro-1-methyl-1H-isoindole maleate (BRL44408), alpha2B-2-[2-(4-(2
methoxyphenyl)piperazin-1-yl)ethyl]-4,4-dimethyl-1,3-(2H,4H)-isoquinolindione
dihydrochloride (ARC239), alpha2C-JP1302, alpha2D-2-(2,3-dihydro-2-methoxy-1,4
benzodioxin-2-yl)-4,5-dihydro-1H-imidazole hydrochloride [RX821002]). The
agonists were studied in male Wistar rats and were administered intravenously in
cumulative doses. The antagonistic compounds were given in a single dose before
the experiment with marsanidine or 7-methylmarsanidine. Pupil diameter was
measured with stereoscopic microscope equipped in green light filter. Marsanidine
and 7-methylmarsanidine exerted marked mydriatic effects. BRL44408, JP1302, and
ARC239 did not cause significant parallel shift to the right of the dose-effect
curves obtained for both imidazolines. In case of yohimbine and RX821002, the
marked parallel shifts of dose-response curves were observed, with the
antagonistic effects of RX821002 more pronounced. In vivo pharmacodynamics
experiment suggests that alpha2D-adrenoceptor subtype is mainly engaged in
mydriatic effects evoked in rats by imidazoline derivatives, in particular by
clonidine.
PMID- 28491014
TI - Decision Support System for Lymphoma Classification.
AB - The diffuse lymphoma is a malignant tumor of lymphoid tissues. It is associated
with abnormal, unlimited and uncontrolled proliferation of lymphoid cells. Until
now, expert pathologists have identified diffuse lymphoma cells disease manually.
This paper introduces automatic system with a friendly user interface to
differentiate between the categories of the diffuse lymphoma cells. This research
is based on the morphological features such as size, perimeter and circularity.
The cell size is a critical element in the classification of diffuse lymphoma
according to international formulation standards. Therefore, the applied
procedures identify lymphoid cell population in digital microscopic images. The
cells are classified using their morphological data according to the
characteristics of each cell such as: circularity, perimeter, area, and color
density. The number of cells is taken into consideration in the developed
approach. Image processing techniques are applied to digital microscopic images
to measure morphological parameters and to overcome image problems such as
overlapping and cell distortion that affect the sensitivity of the measured data.
The developed procedures help the pathologists to come to a decision regarding
the classification of diffuse lymphoma. Moreover, it can be used to train medical
students and young pathologists.
PMID- 28491013
TI - Peptides with 6-Aminohexanoic Acid: Synthesis and Evaluation as Plasmin
Inhibitors.
AB - Fifteen new peptide derivatives of E-aminocaproic acid (EACA) containing the
known fragment -Ala-Phe-Lys- with an affinity for plasmin were synthesised in the
present study. The synthesis was carried out a solid phase. The following
compounds were synthesised: H-Phe-Lys-EACA-X, H-d-Ala-Phe-Lys-EACA-X, H-Ala-Phe
Lys-EACA-X, H-d-Ala-Phe-EACA-X and H-Ala-Phe-EACA-X, where X = OH, NH2 and NH
(CH2)5-NH2. All peptides, except for those containing the sequence H-Ala-Phe-EACA
X, displayed higher inhibitory activity against plasmin than EACA. The most
active and selective inhibitor of plasmin was the compound H-d-Ala-Phe-Lys-EACA
NH2 which inhibited the amidolytic activity of plasmin (IC50 = 0.02 mM), with the
antifibrinolytic activity weaker than EACA. The resulting peptides did not affect
the viability of fibroblast cells, colon cancer cell line DLD-1, breast MCF-7 and
MDA-MB-231 cell lines.
PMID- 28491015
TI - Protocols for Visually Guided Navigation Assessment of Efficacy of Retina
Directed Cell or Gene Therapy in Canines.
AB - There has been marked progress in recent years in developing gene delivery
approaches for the treatment of inherited blinding diseases. Many of the proof-of
concept studies have utilized rodent models of retinal degeneration. In those
models, tests of visual function include a modified water maze swim test,
optokinetic nystagmus, and light-dark activity assays. Test paradigms used in
rodents can be difficult to replicate in large animals due to their size and
awareness of non-visual aspects of the test system. Two types of visual behavior
assays have been utilized in canines: an obstacle avoidance course and a forced
choice Y maze. Given the progress in developing cell and gene therapies in large
animals, such tests will become more and more valuable. This study provides
guidelines for carrying out such tests and assesses the challenges and benefits
associated with each test.
PMID- 28491016
TI - A Channel Rejection Method for Attenuating Motion-Related Artifacts in EEG
Recordings during Walking.
AB - Recording scalp electroencephalography (EEG) during human motion can introduce
motion artifacts. Repetitive head movements can generate artifact patterns across
scalp EEG sensors. There are many methods for identifying and rejecting bad
channels and independent components from EEG datasets, but there is a lack of
methods dedicated to evaluate specific intra-channel amplitude patterns for
identifying motion-related artifacts. In this study, we proposed a template
correlation rejection (TCR) as a novel method for identifying and rejecting EEG
channels and independent components carrying motion-related artifacts. We
recorded EEG data from 10 subjects during treadmill walking. The template
correlation rejection method consists of creating templates of amplitude patterns
and determining the fraction of total epochs presenting relevant correlation to
the template. For EEG channels, the template correlation rejection removed
channels presenting the majority of epochs (>75%) correlated to the template, and
presenting pronounced amplitude in comparison to all recorded channels. For
independent components, the template correlation rejection removed components
presenting the majority of epochs correlated to the template. Evaluation of scalp
maps and power spectra confirmed low neural content for the rejected components.
We found that channels identified for rejection contained ~60% higher delta
power, and had spectral properties locked to the gait phases. After rejecting the
identified channels and running independent component analysis on the EEG
datasets, the proposed method identified 4.3 +/- 1.8 independent components (out
of 198 +/- 12) with substantive motion-related artifacts. These results indicate
that template correlation rejection is an effective method for rejecting EEG
channels contaminated with motion-related artifact during human locomotion.
PMID- 28491017
TI - Opinion: Inhibition of Blood-Brain Barrier Repair as a Mechanism in HIV-1
Disease.
PMID- 28491018
TI - Transcranial Stimulation of the Orbitofrontal Cortex Affects Decisions about
Magnocellular Optimized Stimuli.
AB - Visual categorization plays an important role in fast and efficient information
processing; still the neuronal basis of fast categorization has not been
established yet. There are two main hypotheses known; both agree that primary,
global impressions are based on the information acquired through the
magnocellular pathway (MC). It is unclear whether this information is available
through the MC that provides information (also) for the ventral pathway or
through top-down mechanisms by connections between the dorsal pathway and the
ventral pathway via the frontal cortex. To clarify this, a categorization task
was performed by 48 subjects; they had to make decisions about objects' sizes. We
created stimuli specific to the magno- and parvocellular pathway (PC) on the
basis of their spatial frequency content. Transcranial direct-current stimulation
was used to assess the role of frontal areas, a target of the MC. Stimulation did
not bias the accuracy of decisions when stimuli optimized for the PC were used.
In the case of stimuli optimized for the MC, anodal stimulation improved the
subjects' accuracy in the behavioral test, while cathodal stimulation impaired
accuracy. Our results support the hypothesis that fast visual categorization
processes rely on top-down mechanisms that promote fast predictions through
coarse information carried by MC via the orbitofrontal cortex.
PMID- 28491020
TI - Corrigendum: Structural Brain Network Reorganization and Social Cognition Related
to Adverse Perinatal Condition from Infancy to Early Adolescence.
AB - [This corrects the article on p. 560 in vol. 10, PMID: 28008304.].
PMID- 28491021
TI - Corrigendum: Brain Metabolic Changes in Rats following Acoustic Trauma.
AB - [This corrects the article on p. 148 in vol. 11, PMID: 28392756.].
PMID- 28491019
TI - Shared and Differential Retinal Responses against Optic Nerve Injury and Ocular
Hypertension.
AB - Glaucoma, one of the leading causes of blindness worldwide, affects primarily
retinal ganglion cells (RGCs) and their axons. The pathophysiology of glaucoma is
not fully understood, but it is currently believed that damage to RGC axons at
the optic nerve head plays a major role. Rodent models to study glaucoma include
those that mimic either ocular hypertension or optic nerve injury. Here we review
the anatomical loss of the general population of RGCs (that express Brn3a;
Brn3a+RGCs) and of the intrinsically photosensitive RGCs (that express
melanopsin; m+RGCs) after chronic (LP-OHT) or acute (A-OHT) ocular hypertension
and after complete intraorbital optic nerve transection (ONT) or crush (ONC). Our
studies show that all of these insults trigger RGC death. Compared to Brn3a+RGCs,
m+RGCs are more resilient to ONT, ONC, and A-OHT but not to LP-OHT. There are
differences in the course of RGC loss both between these RGC types and among
injuries. An important difference between the damage caused by ocular
hypertension or optic nerve injury appears in the outer retina. Both axotomy and
LP-OHT induce selective loss of RGCs but LP-OHT also induces a protracted loss of
cone photoreceptors. This review outlines our current understanding of the
anatomical changes occurring in rodent models of glaucoma and discusses the
advantages of each one and their translational value.
PMID- 28491022
TI - Corrigendum: Auditory Spatial Recalibration in Congenital Blind Individuals.
AB - [This corrects the article on p. 76 in vol. 11, PMID: 28261053.].
PMID- 28491023
TI - Characterization of the Transcriptomes of Lgr5+ Hair Cell Progenitors and Lgr5-
Supporting Cells in the Mouse Cochlea.
AB - Cochlear supporting cells (SCs) have been shown to be a promising resource for
hair cell (HC) regeneration in the neonatal mouse cochlea. Previous studies have
reported that Lgr5+ SCs can regenerate HCs both in vitro and in vivo and thus are
considered to be inner ear progenitor cells. Lgr5+ progenitors are able to
regenerate more HCs than Lgr5- SCs, and it is important to understand the
mechanism behind the proliferation and HC regeneration of these progenitors.
Here, we isolated Lgr5+ progenitors and Lgr5- SCs from Lgr5-EGFP-CreERT2/Sox2
CreERT2/Rosa26-tdTomato mice via flow cytometry. As expected, we found that Lgr5+
progenitors had significantly higher proliferation and HC regeneration ability
than Lgr5- SCs. Next, we performed RNA-Seq to determine the gene expression
profiles of Lgr5+ progenitors and Lgr5- SCs. We analyzed the genes that were
enriched and differentially expressed in Lgr5+ progenitors and Lgr5- SCs, and we
found 8 cell cycle genes, 9 transcription factors, and 24 cell signaling pathway
genes that were uniquely expressed in one population but not the other. Last, we
made a protein-protein interaction network to further analyze the role of these
differentially expressed genes. In conclusion, we present a set of genes that
might regulate the proliferation and HC regeneration ability of Lgr5+
progenitors, and these might serve as potential new therapeutic targets for HC
regeneration.
PMID- 28491025
TI - Change of Rin1 and Stathmin in the Animal Model of Traumatic Stresses.
AB - The molecular mechanism of fear memory is poorly understood. Therefore, the
pathogenesis of post-traumatic stress disorder (PTSD), whose symptom presentation
can enhance fear memory, remains largely unclear. Recent studies with knockout
animals have reported that Rin1 and stathmin regulate fear memory. Rin1 inhibits
acquisition and promotes memory extinction, whereas stathmin regulates innate and
basal fear. The aim of our study was to examine changes in the expression of Rin1
and stathmin in different animal models of stress, particluarly traumatic stress.
We used three animal traumatic stresses: single prolonged stress (SPS, which is a
rodent model of PTSD), an immobilization-stress (IM) and a Loud sound stress
(LSS), to examine the change and uniqueness in Rin1/stathmin expression.
Behavioral tests of SPS rats demonstrated increased anxiety and contextual fear
conditioning. They showed decreased long-term potentiation (LTP), as well as
decreased stathmin and increased Rin1 expression in the hippocampus and the
amygdala. Expression of the stathmin effector, tubulin, and downstream molecules
Rin1, Rab5, and Abl, appeared to increase. Rin1 and EphA4 were endogenously
coexpressed in primary neurons after SPS stimulation. IM rats exhibited increased
anxiety behavior and enhanced fear-conditioning to contextual and auditory
stimuli. Similar changes in expression of Rin1/stathmin were observed in IM rats
whereas no changes were observed in rats exposed to a loud sound. These data
suggest that changes in expression of the Rin1 and stathmin genes may be involved
in rodents with SPS and IM stresses, which provide valuable insight into fear
memories under abnormal conditions, particularly in PTSD.
PMID- 28491024
TI - The Serotonin Transporter and Early Life Stress: Translational Perspectives.
AB - The interaction between the serotonin transporter (SERT) linked polymorphic
region (5-HTTLPR) and adverse early life stressing (ELS) events is associated
with enhanced stress susceptibility and risk to develop mental disorders like
major depression, anxiety, and aggressiveness. In particular, human short allele
carriers are at increased risk. This 5-HTTLPR polymorphism is absent in the
rodent SERT gene, but heterozygous SERT knockout rodents (SERT+/-) show several
similarities to the human S-allele carrier, therefore creating an animal model of
the human situation. Many rodent studies investigated ELS interactions in SERT
knockout rodents combined with ELS. However, underlying neuromolecular mechanisms
of the (mal)adaptive responses to adversity displayed by SERT rodents remain to
be elucidated. Here, we provide a comprehensive review including studies
describing mechanisms underlying SERT variation * ELS interactions in rodents.
Alterations at the level of translation and transcription but also epigenetic
alterations considerably contribute to underlying mechanisms of SERT variation *
ELS interactions. In particular, SERT+/- rodents exposed to adverse early rearing
environment may be of high translational and predictive value to the more stress
sensitive human short-allele carrier, considering the similarity in neurochemical
alterations. Therefore, SERT+/- rodents are highly relevant in research that aims
to unravel the complex psychopathology of mental disorders. So far, most studies
fail to show solid evidence for increased vulnerability to develop affective-like
behavior after ELS in SERT+/- rodents. Several reasons may underlie these
failures, e.g., (1) stressors used might not be optimal or severe enough to
induce maladaptations, (2) effects in females are not sufficiently studied, and
(3) few studies include both behavioral manifestations and molecular correlates
of ELS-induced effects in SERT+/- rodents. Of course, one should not exclude the
(although unlikely) possibility of SERT+/- rodents not being sensitive to ELS. In
conclusion, future studies addressing ELS-induced effects in the SERT+/- rodents
should extensively study both long-term behavioral and (epi)genetic aspects in
both sexes. Finally, further research is warranted using more severe stressors in
animal models. From there on, we should be able to draw solid conclusions whether
the SERT+/- exposed to ELS is a suitable translational animal model for studying
5-HTTLPR polymorphism and stress interactions.
PMID- 28491026
TI - "Neural Efficiency" of Athletes' Brain during Visuo-Spatial Task: An fMRI Study
on Table Tennis Players.
AB - Long-term training leads experts to develop a focused and efficient organization
of task-related neural networks. "Neural efficiency" hypothesis posits that
neural activity is reduced in experts. Here we tested the following working
hypotheses: compared to non-athletes, athletes showed lower cortical activation
in task-sensitive brain areas during the processing of sports related and sports
unrelated visuo-spatial tasks. To address this issue, cortical activation was
examined with fMRI in 14 table tennis athletes and 14 non-athletes while
performing the visuo-spatial tasks. Behavioral results showed that athletes
reacted faster than non-athletes during both types of the tasks, and no accuracy
difference was found between athletes and non-athletes. fMRI data showed that,
athletes exhibited less brain activation than non-athletes in the bilateral
middle frontal gyrus, right middle orbitofrontal area, right supplementary motor
area, right paracentral lobule, right precuneus, left supramarginal gyrus, right
angular gyrus, left inferior temporal gyrus, left middle temporal gyrus,
bilateral lingual gyrus and left cerebellum crus. No region was significantly
more activated in the athletes than in the non-athletes. These findings possibly
suggest that long-standing training prompt athletes develop a focused and
efficient organization of task-related neural networks, as a possible index of
"neural efficiency" in athletes engaged in visuo-spatial tasks, and this
functional reorganization is possibly task-specific.
PMID- 28491027
TI - Post-Learning Sleep Transiently Boosts Context Specific Operant Extinction
Memory.
AB - Operant extinction is learning to supress a previously rewarded behavior. It is
known to be strongly associated with the specific context in which it was
acquired, which limits the therapeutic use of operant extinction in behavioral
treatments, e.g., of addiction. We examined whether sleep influences contextual
memory of operant extinction over time, using two different recall tests (Recent
and Remote). Rats were trained in an operant conditioning task (lever press) in
context A, then underwent extinction training in context B, followed by a 3-h
retention period that contained either spontaneous morning sleep, morning sleep
deprivation, or spontaneous evening wakefulness. A recall test was performed
either immediately after the 3-h experimental retention period (Recent recall) or
after 48 h (Remote), in the extinction context B and in a novel context C. The
two main findings were: (i) at the Recent recall test, sleep in comparison with
sleep deprivation and spontaneous wakefulness enhanced extinction memory but,
only in the extinction context B; (ii) at the Remote recall, extinction
performance after sleep was enhanced in both contexts B and C to an extent
comparable to levels at Recent recall in context B. Interestingly, extinction
performance at Remote recall was also improved in the sleep deprivation groups in
both contexts, with no difference to performance in the sleep group. Our results
suggest that 3 h of post-learning sleep transiently facilitate the context
specificity of operant extinction at a Recent recall. However, the improvement
and contextual generalization of operant extinction memory observed in the long
term, i.e., after 48 h, does not require immediate post-learning sleep.
PMID- 28491028
TI - Resting-State Functional Connectivity and Network Analysis of Cerebellum with
Respect to Crystallized IQ and Gender.
AB - During the last years, it has been established that the prefrontal and posterior
parietal brain lobes, which are mostly related to intelligence, have many
connections to cerebellum. However, there is a limited research investigating
cerebellum's relationship with cognitive processes. In this study, the network of
cerebellum was analyzed in order to investigate its overall organization in
individuals with low and high crystallized Intelligence Quotient (IQ). Functional
magnetic resonance imaging (fMRI) data were selected from 136 subjects in resting
state from the Human Connectome Project (HCP) database and were further separated
into two IQ groups composed of 69 low-IQ and 67 high-IQ subjects. Cerebellum was
parcellated into 28 lobules/ROIs (per subject) using a standard cerebellum
anatomical atlas. Thereafter, correlation matrices were constructed by computing
Pearson's correlation coefficients between the average BOLD time-series for each
pair of ROIs inside the cerebellum. By computing conventional graph metrics,
small-world network properties were verified using the weighted clustering
coefficient and the characteristic path length for estimating the trade-off
between segregation and integration. In addition, a connectivity metric was
computed for extracting the average cost per network. The concept of the Minimum
Spanning Tree (MST) was adopted and implemented in order to avoid methodological
biases in graph comparisons and retain only the strongest connections per
network. Subsequently, six global and three local metrics were calculated in
order to retrieve useful features concerning the characteristics of each MST.
Moreover, the local metrics of degree and betweenness centrality were used to
detect hubs, i.e., nodes with high importance. The computed set of metrics gave
rise to extensive statistical analysis in order to examine differences between
low and high-IQ groups, as well as between all possible gender-based group
combinations. Our results reveal that both male and female networks have small
world properties with differences in females (especially in higher IQ females)
indicative of higher neural efficiency in cerebellum. There is a trend toward the
same direction in men, but without significant differences. Finally, three
lobules showed maximum correlation with the median response time in low-IQ
individuals, implying that there is an increased effort dedicated locally by this
population in cognitive tasks.
PMID- 28491029
TI - Sample Entropy, Univariate, and Multivariate Multi-Scale Entropy in Comparison
with Classical Postural Sway Parameters in Young Healthy Adults.
AB - The present study aimed to compare various entropy measures to assess the
dynamics and complexity of center of pressure (COP) displacements. Perturbing
balance tests are often used in healthy subjects to imitate either pathological
conditions or to test the sensitivity of postural analysis techniques. Eleven
healthy adult subjects were asked to stand in normal stance in three experimental
conditions while the visuo-kinesthetic input was altered. COP displacement was
recorded using a force plate. Three entropy measures [Sample Entropy (SE), Multi
Scale Entropy (MSE), and Multivariate Multi Scale Entropy (MMSE)] describing COP
regularity at different scales were compared to traditional measures of COP
variability. The analyses of the COP trajectories revealed that suppression of
vision produced minor changes in COP displacement and in the COP characteristics.
The comparison with the reference analysis showed that the entropy measures
analysis techniques are more sensitive in the incremented time series compared to
the classical parameters and entropy measures of original time series. Non-linear
methods appear to be an additional valuable tool for analysis of the dynamics of
posture especially when applied on incremental time series.
PMID- 28491030
TI - The Encephalophone: A Novel Musical Biofeedback Device using Conscious Control of
Electroencephalogram (EEG).
AB - A novel musical instrument and biofeedback device was created using
electroencephalogram (EEG) posterior dominant rhythm (PDR) or mu rhythm to
control a synthesized piano, which we call the Encephalophone. Alpha-frequency (8
12 Hz) signal power from PDR in the visual cortex or from mu rhythm in the motor
cortex was used to create a power scale which was then converted into a musical
scale, which could be manipulated by the individual in real time. Subjects could
then generate different notes of the scale by activation (event-related
synchronization) or de-activation (event-related desynchronization) of the PDR or
mu rhythms in visual or motor cortex, respectively. Fifteen novice normal
subjects were tested in their ability to hit target notes presented within a 5
min trial period. All 15 subjects were able to perform more accurately (average
of 27.4 hits, 67.1% accuracy for visual cortex/PDR signaling; average of 20.6
hits, 57.1% accuracy for mu signaling) than a random note generation (19.03%
accuracy). Moreover, PDR control was significantly more accurate than mu control.
This shows that novice healthy individuals can control music with better accuracy
than random, with no prior training on the device, and that PDR control is more
accurate than mu control for these novices. Individuals with more years of
musical training showed a moderate positive correlation with more PDR accuracy,
but not mu accuracy. The Encephalophone may have potential applications both as a
novel musical instrument without requiring movement, as well as a potential
therapeutic biofeedback device for patients suffering from motor deficits (e.g.,
amyotrophic lateral sclerosis (ALS), brainstem stroke, traumatic amputation).
PMID- 28491031
TI - Control of Absence Seizures by the Thalamic Feed-Forward Inhibition.
AB - As a subtype of idiopathic generalized epilepsies, absence epilepsy is believed
to be caused by pathological interactions within the corticothalamic (CT) system.
Using a biophysical mean-field model of the CT system, we demonstrate here that
the feed-forward inhibition (FFI) in thalamus, i.e., the pathway from the
cerebral cortex (Ctx) to the thalamic reticular nucleus (TRN) and then to the
specific relay nuclei (SRN) of thalamus that are also directly driven by the Ctx,
may participate in controlling absence seizures. In particular, we show that
increasing the excitatory Ctx-TRN coupling strength can significantly suppress
typical electrical activities during absence seizures. Further, investigation
demonstrates that the GABAA- and GABAB-mediated inhibitions in the TRN-SRN
pathway perform combination roles in the regulation of absence seizures. Overall,
these results may provide an insightful mechanistic understanding of how the
thalamic FFI serves as an intrinsic regulator contributing to the control of
absence seizures.
PMID- 28491033
TI - Corrigendum: A Mixed-Methods Trial of Broad Band Noise and Nature Sounds for
Tinnitus Therapy: Group and Individual Responses Modeled under the Adaptation
Level Theory of Tinnitus.
AB - [This corrects the article on p. 44 in vol. 9, PMID: 28337139.].
PMID- 28491032
TI - Topological Filtering of Dynamic Functional Brain Networks Unfolds Informative
Chronnectomics: A Novel Data-Driven Thresholding Scheme Based on Orthogonal
Minimal Spanning Trees (OMSTs).
AB - The human brain is a large-scale system of functionally connected brain regions.
This system can be modeled as a network, or graph, by dividing the brain into a
set of regions, or "nodes," and quantifying the strength of the connections
between nodes, or "edges," as the temporal correlation in their patterns of
activity. Network analysis, a part of graph theory, provides a set of summary
statistics that can be used to describe complex brain networks in a meaningful
way. The large-scale organization of the brain has features of complex networks
that can be quantified using network measures from graph theory. The adaptation
of both bivariate (mutual information) and multivariate (Granger causality)
connectivity estimators to quantify the synchronization between multichannel
recordings yields a fully connected, weighted, (a)symmetric functional
connectivity graph (FCG), representing the associations among all brain areas.
The aforementioned procedure leads to an extremely dense network of tens up to a
few hundreds of weights. Therefore, this FCG must be filtered out so that the
"true" connectivity pattern can emerge. Here, we compared a large number of well
known topological thresholding techniques with the novel proposed data-driven
scheme based on orthogonal minimal spanning trees (OMSTs). OMSTs filter brain
connectivity networks based on the optimization between the global efficiency of
the network and the cost preserving its wiring. We demonstrated the proposed
method in a large EEG database (N = 101 subjects) with eyes-open (EO) and eyes
closed (EC) tasks by adopting a time-varying approach with the main goal to
extract features that can totally distinguish each subject from the rest of the
set. Additionally, the reliability of the proposed scheme was estimated in a
second case study of fMRI resting-state activity with multiple scans. Our results
demonstrated clearly that the proposed thresholding scheme outperformed a large
list of thresholding schemes based on the recognition accuracy of each subject
compared to the rest of the cohort (EEG). Additionally, the reliability of the
network metrics based on the fMRI static networks was improved based on the
proposed topological filtering scheme. Overall, the proposed algorithm could be
used across neuroimaging and multimodal studies as a common computationally
efficient standardized tool for a great number of neuroscientists and physicists
working on numerous of projects.
PMID- 28491034
TI - Corrigendum: Hearing Impairment Is Associated with Smaller Brain Volume in Aging.
AB - [This corrects the article on p. 2 in vol. 9, PMID: 28163683.].
PMID- 28491035
TI - Proteomic Analysis Reveals Autophagy as Pro-Survival Pathway Elicited by Long
Term Exposure with 5-Azacitidine in High-Risk Myelodysplasia.
AB - Azacytidine (5-AZA) is the standard first-choice treatment for high-risk
myelodysplasia (MDS) patients. However, the clinical outcome for those patients
who interrupt treatment or whose disease failed to respond is very poor. In order
to identify the cellular pathways that are modified by long-term exposure to 5
AZA, we evaluated key proteins associated with the autophagy pathway by reverse
phase microarray (RPPA). Comparing bone marrow mononucleated cells (BMMCs)
obtained from 20 newly-diagnosed patients and after four 5-AZA cycles we found an
increased autophagy signaling. We then evaluated ex-vivo the effect of the
combination of 5-AZA with autophagy inhibitors chloroquine (CQ) and leupeptin.
Since 5-AZA and CQ showed synergism due to an increase of basal autophagy after 5
AZA exposure, we adopted a sequential treatment treating BMMCs with 5 MUM 5-AZA
for 72 h followed by 10 MUM CQ for 24 h and found increased apoptosis, associated
to a reduction of G2M phase and increase in G0-G1 phase. Long-term exposure to 5
AZA induced the reduction of the autophagic marker SQSTM1/p62, reversible by CQ
or leupeptin exposure. In conclusion, we identified autophagy as a compensatory
pathway occurring in MDS-BM after long-term exposure to 5-AZA and we provided
evidences that a sequential treatment of 5-AZA followed by CQ could improve 5-AZA
efficacy, providing novel insight for tailored therapy in MDS patients
progressing after 5-AZA therapy.
PMID- 28491036
TI - Pharmacological Activity and Clinical Use of PDRN.
AB - PDRN is a proprietary and registered drug that possesses several activities:
tissue repairing, anti-ischemic, and anti-inflammatory. These therapeutic
properties suggest its use in regenerative medicine and in diabetic foot ulcers.
PDRN holds a mixture of deoxyribonucleotides with molecular weights ranging
between 50 and 1,500 KDa, it is derived from a controlled purification and
sterilization process of Oncorhynchus mykiss (Salmon Trout) or Oncorhynchus keta
(Chum Salmon) sperm DNA. The procedure guarantees the absence of active protein
and peptides that may cause immune reactions. In vitro and in vivo experiments
have suggested that PDRN most relevant mechanism of action is the engagement of
adenosine A2A receptors. Besides engaging the A2A receptor, PDRN offers
nucleosides and nucleotides for the so called "salvage pathway." The binding to
adenosine A2A receptors is a unique property of PDRN and seems to be linked to
DNA origin, molecular weight and manufacturing process. In this context, PDRN
represents a new advancement in the pharmacotherapy. In fact adenosine and
dipyridamole are non-selective activators of adenosine receptors and they may
cause unwanted side effects; while regadenoson, the only other A2A receptor
agonist available, has been approved by the FDA as a pharmacological stress agent
in myocardial perfusion imaging. Finally, defibrotide, another drug composed by a
mixture of oligonucleotides, has different molecular weight, a DNA of different
origin and does not share the same wound healing stimulating effects of PDRN. The
present review analyses the more relevant experimental and clinical evidences
carried out to characterize PDRN therapeutic effects.
PMID- 28491037
TI - Sodium 4-Carboxymethoxyimino-(4-HPR) a Novel Water-Soluble Derivative of 4-Oxo-4
HPR Endowed with In Vivo Anticancer Activity on Solid Tumors.
AB - 4-oxo-N-(4-hydroxyphenyl)retinamide (4-oxo-4-HPR), an active polar metabolite of
the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR), was shown to exert
promising antitumor activity through at least two independent mechanisms of
action. Specifically, differently from 4-HPR and other retinoids, 4-oxo-4-HPR
targets microtubules and inhibits tubulin polymerization causing mitotic arrest
and on the other hand, analogously to the parent drug, it induces apoptosis
through the activation of a signaling cascade involving the generation of
reactive oxygen species (ROS). However, the potential in vivo use of 4-oxo-4-HPR
is impaired by its poor solubility. By chemical modification of 4-oxo-4-HPR, a
new class of compounds with improved solubility and in vivo bioavailability was
obtained. We demonstrated here that, among them, the most promising molecule,
sodium 4-carboxymethoxyimino-(4-HPR), was endowed with in vitro antitumor
efficacy and entirely preserved the double mechanism of action of the parent drug
in cancer cells of different histotypes. In fact, the retinoid induced the
activation of the apoptotic cascade related to the generation of ROS through
endoplasmic reticulum stress response and upregulation of phospho c-Jun N
terminal kinases and PLAcental Bone morphogenetic protein, leading to cell death
through caspase-3 cleavage. Otherwise, sodium 4-carboxymethoxyimino-(4-HPR)
caused a marked mitotic arrest coupled with multipolar spindle formation and
tubulin depolymerization. To assess the compound antitumor activity, in vivo
experiments were performed in three mouse xenograft models (ovarian and breast
cancers and mesothelioma). The in vivo results demonstrated that retinoid
administration as single agent significantly increased the survival in ovarian
cancer xenografts, induced a statistically significant decrease in tumor growth
in breast cancer xenografts, and caused a 30% reduction in tumor growth in a
mesothelioma mouse model. Even though further studies investigating sodium 4
carboxymethoxyimino-(4-HPR) toxicity and in vitro and in vivo activities in
combination with other drugs are required, the double mechanism of action of the
retinoid coupled with its in vivo antitumor efficacy and potential low toxicity
suggest a promising therapeutic potential for the compound in different solid
tumors.
PMID- 28491038
TI - Yokukansan and Yokukansankachimpihange Ameliorate Aggressive Behaviors in Rats
with Cholinergic Degeneration in the Nucleus Basalis of Meynert.
AB - Yokukansan (YKS) and yokukansankachimpihange (YKSCH) are traditional Japanese
Kampo medicines. The latter comprises YKS along with the medicinal herbs Citrus
unshiu peel and Pinellia tuber. Both of these Kampo medicines are indicated for
the treatment of night crying and irritability in children and for neurosis and
insomnia in adults. In recent clinical trials, YKS exhibited ameliorative effects
on the behavioral and psychological symptoms of dementia, such as aggressiveness,
excitement, and irritability. In the present study, we aimed to clarify the
involvement of cholinergic degeneration in the nucleus basalis of Meynert (NBM)
in the development of aggressiveness in rats. Subsequently, using this animal
model, the effects of YKS and YKSCH on aggressiveness were compared and the
mechanisms underlying these effects were investigated. L-Glutamic acid (Glu) was
injected into the right NBM of rats to induce deterioration of cholinergic
neurons. On day 8 after Glu injection, aggressive behaviors were evaluated using
resident-intruder tests. After the evaluation, YKS or YKSCH was administered to
rats with aggressive behaviors daily for 7 days. In some groups, the 5-HT1A
receptor antagonist WAY-100635 was coadministered with YKS or YKSCH over the same
period. In other groups, locomotor activity was measured on days 12-14 after Glu
injection. On day 15, immunohistochemistry was then performed to examine choline
acetyltransferase (ChAT) activities in the NBM. Aggressive behaviors had
developed on day 8 after Glu injection and were maintained until day 15. YKS and
YKSCH significantly ameliorated the aggressive behaviors. These suppressive
effects were entirely abolished following coadministration of WAY-100635.
Finally, the number of ChAT-positive cells in the right NBM was significantly
reduced on day 15 after Glu injection, and treatment with YKS or YKSCH did not
ameliorate these reduced cell numbers. Our results show that unilateral Glu
injections into the NBM of rats leads to the development of aggressive behaviors,
which is thought to reflect cholinergic degeneration. YKS and YKSCH treatments
ameliorated Glu-induced aggressive behaviors, and these effects were suggested to
be mediated by 5-HT1A receptor stimulation, but not by improvement of cholinergic
degeneration.
PMID- 28491039
TI - Daily Moderate Exercise Is Beneficial and Social Stress Is Detrimental to Disease
Pathology in Murine Lupus Nephritis.
AB - Daily moderate exercise (DME) and stress management are underemphasized in the
care of patients with lupus nephritis (LN) due to a poor comprehensive
understanding of their potential roles in controlling the inflammatory response.
To investigate these effects on murine LN, disease progression was monitored with
either DME or social disruption stress (SDR) induction in NZM2410/J mice, which
spontaneously develop severe, early-onset LN. SDR of previously established
social hierarchies was performed daily for 6 days and DME consisted of treadmill
walking (8.5 m/min for 45 min/day). SDR significantly enhanced kidney disease
when compared to age-matched, randomly selected control counterparts, as measured
by histopathological analysis of H&E staining and immunohistochemistry for
complement component 3 (C3) and IgG complex deposition. Conversely, while 88% of
non-exercised mice displayed significant renal damage by 43 weeks of age, this
was reduced to 45% with exercise. DME also reduced histopathology in kidney
tissue and significantly decreased deposits of C3 and IgG complexes. Further
examination of renal infiltrates revealed a macrophage-mediated inflammatory
response that was significantly induced with SDR and suppressed with DME, which
also correlated with expression of inflammatory mediators. Specifically, SDR
induced IL-6, TNF-alpha, IL-1beta, and MCP-1, while DME suppressed IL-6, TNF
alpha, IL-10, CXCL1, and anti-dsDNA autoantibodies. These data demonstrate that
psychological stressors and DME have significant, but opposing effects on the
chronic inflammation associated with LN; thus identifying and characterizing
stress reduction and a daily regimen of physical activity as potential adjunct
therapies to complement pharmacological intervention in the management of
autoimmune disorders, including LN.
PMID- 28491040
TI - Association between Carotid Intima Media Thickness and Heart Rate Variability in
Adults at Increased Cardiovascular Risk.
AB - Background: Atherosclerotic carotid intima-media thickness (IMT) may be
associated with alterations in the sensitivity of carotid baroreceptors. The aim
of this study was to investigate the association between carotid IMT and the
autonomic modulation of heart rate variability (HRV). Methods: A total of 101
subjects were enrolled in this prospective observational study. The carotid IMT
was determined by duplex ultrasonography. The cardiac autonomic function was
determined through HRV measures during the Deep Breathing Test. Linear regression
models, adjusted for demographics, comorbidities, body mass index, waist-hip
ratio, and left ventricular ejection fraction were used to evaluate the
association between HRV parameters and carotid IMT. Results: Participants had a
mean age of 60.4 +/- 13.4 years and an estimated 10-year atherosclerotic
cardiovascular disease (ASCVD) risk score (using the Pooled Cohort Equations) of
16.4 +/- 17. The mean carotid media thickness was highest (0.90 +/- 0.19 mm) in
the first quartile of the standard deviation of all RR intervals (SDNN) (19.7 +/-
5.1 ms) and progressively declined in each subsequent quartile to 0.82 +/- 0.21
mm, 0.81 +/- 0.16 mm, and 0.68 +/- 0.19 in quartiles 2 (36.5 +/- 5.9 ms), 3 (57.7
+/- 6.2 ms) and 4 (100.9 +/- 22.2 ms), respectively. In multivariable adjusted
models, there was a statistical significant association between SDNN and carotid
IMT (OR -0.002; 95%CI -0.003 to -0.001, p = 0.005). The same significant
association was found between carotid IMT and other measures of HRV, including
coefficient of variation of RR intervals (CV) and dispersion of points along the
line of identity (SD2). Conclusions: In a cohort of individuals at increased
cardiovascular risk, carotid IMT as a marker of subclinical atherosclerosis was
associated with alterations of HRV indicating an impaired cardiac autonomic
control, independently of other cardiovascular risk factors.
PMID- 28491041
TI - Describing the Diapause-Preparatory Proteome of the Beetle Colaphellus bowringi
and Identifying Candidates Affecting Lipid Accumulation Using Isobaric Tags for
Mass Spectrometry-Based Proteome Quantification (iTRAQ).
AB - Prior to entering diapause, insects must prepare themselves physiologically to
withstand the stresses of arresting their development for a lengthy period. While
studies describing the biochemical and cellular milieu of the maintenance phase
of diapause are accumulating, few studies have taken an "omics" approach to
describing molecular events during the diapause preparatory phase. We used
isobaric tags and mass spectrometry (iTRAQ) to quantitatively compare the
expression profiles of proteins identified during the onset of diapause
preparation phase in the heads of adult female cabbage beetles, Colaphellus
bowringi. A total of 3,175 proteins were identified, 297 of which were
differentially expressed between diapause-destined and non-diapause-destined
female adults and could therefore be involved in diapause preparation in this
species. Comparison of identified proteins with protein function databases shows
that many of these differentially expressed proteins enhanced in diapause
destined beetles are involved in energy production and conversion, carbohydrate
metabolism and transport, and lipid metabolism. Further hand annotation of
differentially abundant peptides nominates several associated with stress
hardiness, including HSPs and antioxidants, as well as neural development. In
contrast, non-diapause destined beetles show substantial increases in cuticle
proteins, suggesting additional post-emergence growth. Using RNA interference to
silence a fatty acid-binding protein (FABP) that was highly abundant in the head
of diapause-destined females prevented the accumulation of lipids in the fat
body, a common product of diapause preparation in this species and others.
Surprisingly, RNAi against the FABP also affected the transcript abundance of
several heat shock proteins. These results suggest that the identified
differentially expressed proteins that play vital roles in lipid metabolism may
also contribute somehow to enhanced hardiness to environmental stress that is
characteristic of diapause.
PMID- 28491043
TI - A Comparison of Children's Ability to Read Children's and Adults' Mental States
in an Adaptation of the Reading the Mind in the Eyes Task.
AB - The ability to read mental states from subtle facial cues is an important part of
Theory of Mind, which can contribute to children's daily life social functioning.
Mental state reading performance is influenced by the specific interactions in
which it is applied; familiarity with characteristics of these interactions (such
as the person) can enhance performance. The aim of this research is to gain
insight in this context effect for mental state reading in children, assessed
with the Reading the Mind in the Eyes (RME) task that originally consists of
pictures of adults' eyes. Because of differences between children and adults in
roles, development and frequency of interaction, children are more familiar with
mental state reading of other children. It can therefore be expected that
children's mental state reading depends on whether this is assessed with
children's or adults' eyes. A new 14 item version of the RME for children was
constructed with pictures of children instead of adults (study 1). This task was
used and compared to the original child RME in 6-10 year olds (N = 718, study 2)
and 8-14 year olds (N = 182, study 3). Children in both groups performed better
on the new RME than on the original RME. Item level findings of the new RME were
in line with previous findings on the task and test re-test reliability (in a
subgroup of older children, n = 95) was adequate (0.47). This suggests that the
RME with children's eyes can assess children's daily life mental state reading
and supplement existing ToM tasks.
PMID- 28491042
TI - Disentangling Working Memory Functioning in Mood States of Bipolar Disorder: A
Systematic Review.
AB - Working memory (WM) deficits are often reported in patients with Bipolar Disorder
(BD). However, it is not clear about the nature of these WM deficits (update or
serial order processes) and their association with each BD states (euthymic,
mania, and depressive). This review investigated the association between BD
patient's states and the functioning of WM components. For this purpose, we
carried out a systematic review fulfilling a search in the databases Medline,
Scopus, SciELO, and Web of Science using specific terms in the abstracts of the
articles that generated 212 outcomes in the restricted period from 2005 to 2016.
Twenty-three papers were selected, completely read, and analyzed using PICOS
strategy. The mood episodes predicted deficits in different components of WM in
BD patients (the phonological loop or visuospatial sketchpad) and were associated
with different WM processes (updating and serial recall). Lower cognitive scores
persist even in remission of symptoms. This result suggests that WM deficit
apparently is stage-independent in BD patients. Furthermore, findings suggest
that the neutral point on Hedonic Detector component of WM could be maladjusted
by BD.
PMID- 28491044
TI - Music to Make Your Mouth Water? Assessing the Potential Influence of Sour Music
on Salivation.
AB - People robustly associate various sound attributes with specific smells/tastes,
and soundtracks that are associated with specific tastes can influence people's
evaluation of the taste of food and drink. However, it is currently unknown
whether such soundtracks directly impact the eating experience via physiological
changes (an embodiment account), or whether they act at a higher cognitive level,
or both. The present research assessed a version of the embodiment account, where
a soundtrack associated with sourness is hypothesized to induce a physiological
response in the listener by increasing salivary flow. Salivation was measured
while participants were exposed to three different experimental conditions - a
sour soundtrack, a muted lemon video showing a man eating a lemon, and a silent
baseline condition. The results revealed that salivation during the lemon video
condition was significantly greater than in the sour soundtrack and baseline
conditions. However, contrary to our hypothesis, there was no significant
difference between salivation levels in the sour soundtrack compared to the
baseline condition. These results are discussed in terms of potential mechanisms
underlying the auditory modulation of taste perception/evaluation.
PMID- 28491045
TI - Modeling Timbre Similarity of Short Music Clips.
AB - There is evidence from a number of recent studies that most listeners are able to
extract information related to song identity, emotion, or genre from music
excerpts with durations in the range of tenths of seconds. Because of these very
short durations, timbre as a multifaceted auditory attribute appears as a
plausible candidate for the type of features that listeners make use of when
processing short music excerpts. However, the importance of timbre in listening
tasks that involve short excerpts has not yet been demonstrated empirically.
Hence, the goal of this study was to develop a method that allows to explore to
what degree similarity judgments of short music clips can be modeled with low
level acoustic features related to timbre. We utilized the similarity data from
two large samples of participants: Sample I was obtained via an online survey,
used 16 clips of 400 ms length, and contained responses of 137,339 participants.
Sample II was collected in a lab environment, used 16 clips of 800 ms length, and
contained responses from 648 participants. Our model used two sets of audio
features which included commonly used timbre descriptors and the well-known Mel
frequency cepstral coefficients as well as their temporal derivates. In order to
predict pairwise similarities, the resulting distances between clips in terms of
their audio features were used as predictor variables with partial least-squares
regression. We found that a sparse selection of three to seven features from both
descriptor sets-mainly encoding the coarse shape of the spectrum as well as
spectrotemporal variability-best predicted similarities across the two sets of
sounds. Notably, the inclusion of non-acoustic predictors of musical genre and
record release date allowed much better generalization performance and explained
up to 50% of shared variance (R2) between observations and model predictions.
Overall, the results of this study empirically demonstrate that both acoustic
features related to timbre as well as higher level categorical features such as
musical genre play a major role in the perception of short music clips.
PMID- 28491046
TI - 'The More We Stand For - The More We Fight For': Compatibility and Legitimacy in
the Effects of Multiple Social Identities.
AB - This paper explores the expression of multiple social identities through
coordinated collective action. We propose that perceived compatibility between
potentially contrasting identities and perceived legitimacy of protest serve as
catalysts for collective action. The present paper maps the context of the
"Euromaidan" anti-regime protests in Ukraine and reports data (N = 996) collected
through an online survey following legislation to ban protests (March-May, 2014).
We measured participants' identification with three different groups (the
Ukrainian nation, the online protest community, and the street movement),
perception of compatibility between online protest and the street movement,
perception of the legitimacy of protest, and intentions to take persuasive and
confrontational collective action. We found evidence that the more social groups
people "stood for," the more they "fought" for their cause and that
identifications predicted both forms of collective action to the degree that
people saw the protest and the online movement as compatible with each other and
believed protest to be legitimate. Collective action can be interpreted as the
congruent expression of multiple identities that are rendered ideologically
compatible both in online settings and on the street.
PMID- 28491047
TI - Upper Limb Asymmetry in the Sense of Effort Is Dependent on Force Level.
AB - Previous studies have shown that asymmetries in upper limb sensorimotor function
are dependent on the source of sensory and motor information, hand preference and
differences in hand strength. Further, the utilization of sensory and motor
information and the mode of control of force may differ between the right
hand/left hemisphere and left hand/right hemisphere systems. To more clearly
understand the unique contribution of hand strength and intrinsic differences to
the control of grasp force, we investigated hand/hemisphere differences when the
source of force information was encoded at two different force levels
corresponding to a 20 and 70% maximum voluntary contraction or the right and left
hand of each participant. Eleven, adult males who demonstrated a stronger right
than left maximum grasp force were requested to match a right or left hand 20 or
70% maximal voluntary contraction reference force with the opposite hand. During
the matching task, visual feedback corresponding to the production of the
reference force was available and then removed when the contralateral hand
performed the match. The matching relative force error was significantly
different between hands for the 70% MVC reference force but not for the 20% MVC
reference force. Directional asymmetries, quantified as the matching force
constant error, showed right hand overshoots and left undershoots were force
dependent and primarily due to greater undershoots when matching with the left
hand the right hand reference force. Findings further suggest that the
interaction between internal sources of information, such as efferent copy and
proprioception, as well as hand strength differences appear to be hand/hemisphere
system dependent. Investigations of force matching tasks under conditions whereby
force level is varied and visual feedback of the reference force is available
provides critical baseline information for building effective interventions for
asymmetric (stroke-related, Parkinson's Disease) and symmetric (Amyotrophic
Lateral Sclerosis) upper limb recovery of neurological conditions where the
various sources of sensory - motor information have been significantly altered by
the disease process.
PMID- 28491048
TI - Both the "What" and "Why" of Youth Sports Participation Matter; a Conditional
Process Analysis.
AB - This study builds on previous research combining achievement goal orientation
from Achievement Goal Theory and motivational regulation from Self-Determination
Theory. The aim was to assess the combination of the "what" and "why" of youth
sport activity, and how it relates to the need for competence and self-esteem.
Achievement goal orientation, specifically task and ego, was employed to
represent the "what", whilst intrinsic and external regulation reflected the
"why". Based on a sample of 496 youth sports participants, structural equation
modeling with a bootstrapping procedure was used to examine whether the indirect
relationship between achievement goal orientation and self-esteem was conditional
to motivational regulation. The results show partial support for the conditional
process models. Specifically, task orientation was indirectly linked with self
esteem through competence need, and the relationship was stronger with higher
levels of intrinsic regulation for sport. Furthermore, ego orientation was
negatively associated with self-esteem through a positive relationship with
competence frustration. However, this relationship emerged only for those higher
in intrinsic regulation. External regulation did not emerge as a moderator, but
presented a positive relationship with competence frustration. Findings are
discussed in light of both Achievement Goal Theory and Self-Determination Theory,
and underline the importance of considering both the "what" and "why" when
attempting to understand motivation in youth sport.
PMID- 28491049
TI - Sleep Disturbances in Phenylketonuria: An Explorative Study in Men and Mice.
AB - Sleep problems have not been directly reported in phenylketonuria (PKU). In PKU,
the metabolic pathway of phenylalanine is disrupted, which, among others, causes
deficits in the neurotransmitters and sleep modulators dopamine, norepinephrine,
and serotonin. Understanding sleep problems in PKU patients may help explain the
pathophysiology of brain dysfunction in PKU patients. In this explorative study,
we investigated possible sleep problems in adult treated PKU patients and
untreated PKU mice. In the PKU patients, sleep characteristics were compared to
healthy first degree relatives by assessment of sleep disturbances, sleep-wake
patterns, and sleepiness with the help of four questionnaires: Holland sleep
disorder questionnaire, Pittsburgh sleep quality index, Epworth sleepiness scale,
and Munich Chronotype Questionnaire. The results obtained with the questionnaires
show that PKU individuals suffer more from sleep disorders, a reduced sleep
quality, and an increased latency to fall asleep and experience more sleepiness
during the day. In the PKU mice, activity patterns were recorded with passive
infrared recorders. PKU mice switched more often between active and non-active
behavior and shifted a part of their resting behavior into the active period,
confirming that sleep quality is affected as a consequence of PKU. Together,
these results give the first indication that sleep problems are present in PKU.
More detailed future research will give a better understanding of these problems,
which could ultimately result in the improvement of treatment strategies by
including sleep quality as an additional treatment target.
PMID- 28491050
TI - A Persistent Primitive Hypoglossal Artery As the Sole Supply to the Brain
Associated with a Basilar Bifurcation Aneurysm.
AB - The persistent primitive hypoglossal artery (PPHA) is the second most common
persistent carotid-vertebrobasilar anastomosis, with an incidence of 0.027-0.26%.
PPHAs change the hemodynamics of the carotid and vertebrobasilar system and may
be associated with intracranial vascular anomalies, but basilar bifurcation
aneurysms were rarely reported. We describe the first case of a PPHA as the sole
supply to the brain associated with a basilar bifurcation aneurysm and review the
literature. We reported a 34-year-old woman who presented with subarachnoid
hemorrhage due to a ruptured basilar bifurcation aneurysm. Digital subtraction
arteriogram revealed a right PPHA as the sole supply to the brain. The aneurysm
was successfully clipped under intraoperative neurophysiology.
PMID- 28491051
TI - Hashimoto's Thyroiditis and Autoimmune Gastritis.
AB - The term "thyrogastric syndrome" defines the association between autoimmune
thyroid disease and chronic autoimmune gastritis (CAG), and it was first
described in the early 1960s. More recently, this association has been included
in polyglandular autoimmune syndrome type IIIb, in which autoimmune thyroiditis
represents the pivotal disorder. Hashimoto's thyroiditis (HT) is the most
frequent autoimmune disease, and it has been reported to be associated with
gastric disorders in 10-40% of patients while about 40% of patients with
autoimmune gastritis also present HT. Some intriguing similarities have been
described about the pathogenic mechanism of these two disorders, involving a
complex interaction among genetic, embryological, immunologic, and environmental
factors. CAG is characterized by a partial or total disappearance of parietal
cells implying the impairment of both hydrochloric acid and intrinsic factor
production. The clinical outcome of this gastric damage is the occurrence of a
hypochlorhydric-dependent iron-deficient anemia, followed by pernicious anemia
concomitant with the progression to a severe gastric atrophy. Malabsorption of
levothyroxine may occur as well. We have briefly summarized in this minireview
the most recent achievements on this peculiar association of diseases that, in
the last years, have been increasingly diagnosed.
PMID- 28491052
TI - Receptor-Mediated Melanoma Targeting with Radiolabeled alpha-Melanocyte
Stimulating Hormone: Relevance of the Net Charge of the Ligand.
AB - A majority of melanotic and amelanotic melanomas overexpress melanocortin type 1
receptors (MC1Rs) for alpha-melanocyte-stimulating hormone. Radiolabeled linear
or cyclic analogs of alpha-MSH have a great potential as diagnostic or
therapeutic tools for the management of malignant melanoma. Compounds such as
[111In]DOTA-NAP-amide exhibit high affinity for the MC1R in vitro, good tumor
uptake in vivo, but they may suffer from relatively high kidney uptake and
retention in vivo. We have shown previously that the introduction of negative
charges into radiolabeled DOTA-NAP-amide peptide analogs may enhance their
excretion and reduce kidney retention. To address the question of where to place
negative charges within the ligand, we have extended these studies by designing
two novel peptides, Ac-Nle-Asp-His-d-Phe-Arg-Trp-Gly-Lys(DOTA)-d-Asp-d-Asp-OH
(DOTA-NAP-d-Asp-d-Asp) with three negative charges at the C-terminal end (overall
net charge of the molecule -2) and DOTA-Gly-Tyr(P)-Nle-Asp-His-d-Phe-Arg-Trp-NH2
(DOTA-Phospho-MSH2-9) with two negative charges in the N-terminal region (net
charge -1). The former peptide showed markedly reduced receptor affinity and
biological activity by >10-fold compared to DOTA-NAP-amide as reference compound,
and the latter peptide displayed similar bioactivity and receptor affinity as the
reference compound. The uptake by melanoma tumor tissue of [111In]DOTA-Phospho
MSH2-9 was 7.33 +/- 0.47 %ID/g 4 h after injection, i.e., almost equally high as
with [111In]DOTA-NAP-amide. The kidney retention was 2.68 +/- 0.18 %ID/g 4 h
after injection and hence 44% lower than that of [111In]DOTA-NAP-amide. Over an
observation period from 4 to 48 h, the tumor-to-kidney ratio of [111In]DOTA
Phospho-MSH2-9 was 35% more favorable than that of the reference compound. In a
comparison of DOTA-NAP-d-Asp-d-Asp, DOTA-Phospho-MSH2-9 and DOTA-NAP-amide with
five previously published analogs of DOTA-NAP-amide that altogether cover a range
of peptides with an overall net charge between +2 and -2, we now demonstrate that
a net charge of -1, with the extra negative charges preferably placed in the N
terminal region, has led to the lowest kidney uptake and retention. Charges of +2
or -2 markedly increased kidney uptake and retention. In conclusion, the novel
DOTA-Phospho-MSH2-9 may represent a new lead compound for negatively charged
linear MC1R ligands that can be further developed into a clinically relevant
melanoma targeting radiopeptide.
PMID- 28491053
TI - Hydrophobicity of Residue 128 of the Stress-Inducible Sigma Factor RpoS Is
Critical for Its Activity.
AB - RpoS is a key stress-inducible sigma factor that regulates stress resistance
genes in Escherichia coli, such as the katE gene encoding catalase HPII and the
glg genes encoding glycogen synthesis proteins. Monitoring RpoS activity can
provide information on the stress sensitivity of E. coli isolates in clinical
settings because the RpoS in these isolates is often mutated. In the present
study, we found a novel, missense point mutation at RpoS residue 128 in a
clinical Shiga toxin-producing E. coli (STEC) isolate. This mutation caused RpoS
dysfunction and increased stress sensitivity. A mutant rpoS was cloned from a
clinical STEC that is vulnerable to cold temperature and oxidative stresses.
Mutant RpoS protein expression was detected in the clinical isolate, and this
RpoS was non-functional according to HPII activity and glycogen levels, which are
positively regulated by RpoS and thus are used as indicators for RpoS function. A
reporter assay with beta-galactosidase indicated that the dysfunction occurred at
the transcriptional level of genes regulated by RpoS. Furthermore, substitution
analysis indicated that the hydrophobicity of the amino acid at residue 128 was
critical for RpoS activity; the simulation analysis indicated that the amino
acids of RNA polymerase (RNAP) that interact with RpoS residue 128 are
hydrophobic, suggesting that this hydrophobic interaction is critical for RpoS
activity. In addition, substitution of Ile128 to Pro128 abolished RpoS activity,
possibly as a result of disruption of the secondsary structure around residue
128, indicating that the structure is also a crucial factor for RpoS activity.
These results indicate that only one point mutation at a hydrophobic residue of
the complex formed during transcription leads to a critical change in RpoS
regulation. Moreover, we found that Ile128 is widely conserved among various
bacteria: several bacterial strains have Met128 or Leu128, which are hydrophobic
residues, and these strains had similar or higher RpoS activity than that
observed with Ile128 in this study. These data indicate that the hydrophobicity
of the amino acid at residue 128 is critical for RpoS activity and is
consequently important for bacterial survival. Taken together, these findings may
contribute to a deeper understanding of protein functional mechanisms and
bacterial stress responses.
PMID- 28491054
TI - Flexible Carbon-Use Efficiency across Litter Types and during Decomposition
Partly Compensates Nutrient Imbalances-Results from Analytical Stoichiometric
Models.
AB - Mathematical models involving explicit representations of microbial processes
have been developed to infer microbial community properties from laboratory and
field measurements. While this approach has been used to estimate the kinetic
constants related to microbial activity, it has not been fully exploited for
inference of stoichiometric traits, such as carbon-use efficiency (CUE). Here, a
hierarchy of analytically-solvable mass-balance models of litter carbon (C) and
nitrogen (N) dynamics is developed, to infer decomposer CUE from measured C and N
contents during litter decomposition. The models are solved in the phase space
expressing litter remaining N as a function of remaining C-rather than in time,
thus focusing on the stoichiometric relations during decomposition rather than
the kinetics of degradation. This approach leads to explicit formulas that depend
on CUE and other microbial properties, which can then be treated as model
parameters and retrieved via nonlinear regression. CUE is either assumed time
invariant or as a function of the fraction of remaining litter C as a substitute
for time. In all models, CUE tends to increase with increasing litter N
availability across a range of litter types. When temporal trends in CUE are
considered, CUE increases during decomposition of N-poor litter cohorts, in which
decomposers are initially N-limited, but decreases in N-rich litter possibly due
to C-limitation. These patterns of flexible CUE that partly compensate
stoichiometric imbalances are robust to moderate shifts in decomposer C:N ratio
and hold across wide climatic gradients.
PMID- 28491055
TI - Metagenomic Sequencing of Diamondback Moth Gut Microbiome Unveils Key Holobiont
Adaptations for Herbivory.
AB - Herbivore specialists adapt to feed on a specific group of host plants by
evolving various mechanisms to respond to plant defenses. Insects also possess
complex gut microbiotas but their potential role in adaptation is poorly
understood. Our previous study of the genome of diamondback moth, Plutella
xylostella, revealed an intrinsic capacity to detoxify plant defense compounds,
which is an important factor in its success as a pest. Here we expand on that
work with a complete taxonomic and functional profile of the P. xylostella gut
microbiota obtained by metagenomic sequencing. Gene enrichment in the metagenome,
accompanied by functional identification, revealed an important role of specific
gut bacteria in the breakdown of plant cell walls, detoxification of plant
phenolics, and synthesis of amino acids. Microbes participating in these pathways
mainly belonged to three highly abundant bacteria: Enterobacter cloacae,
Enterobacter asburiae, and Carnobacterium maltaromaticum. Results show that while
the gut microbial community may be complex, a small number of functionally active
species can be disproportionally important. The presence of specific enzymes in
the microbiota community, such as supporting amino acid synthesis, digestion and
detoxification functions, demonstrates the beneficial interactions between P.
xylostella and its gut microbiota. These interactions can be potential targets
for manipulation to provide novel pest management approaches.
PMID- 28491056
TI - Prochlorococcus as a Possible Source for Transparent Exopolymer Particles (TEP).
AB - Transparent exopolymer particles (TEP), usually associated with phytoplankton
blooms, promote the formation of marine aggregates. Their exportation to deep
waters is considered a key component of the biological carbon pump. Here, we
explored the role of solar radiation and picocyanobacteria in the formation of
TEP in oligotrophic surface waters of the Atlantic and Pacific Oceans in ten on
deck incubation experiments during the Malaspina 2010 Expedition. TEP
concentrations were low on the ocean's surface although these concentrations were
significantly higher on the surface of the Pacific (24.45 +/- 2.3 MUg XG Eq. L-1)
than on the surface of the Atlantic Ocean (8.18 +/- 4.56 MUg XG Eq. L-1). Solar
radiation induced a significant production of TEP in the on-deck experiments from
the surface water of the Pacific Ocean, reaching values up to 187.3 MUg XG Eq. L
1 compared with the low production observed in the dark controls. By contrast,
TEP production in the Atlantic Ocean experiments was lower, and its formation was
not related to the light treatments. Prochlorococcus sp. from the surface ocean
was very sensitive to solar radiation and experienced a high cell decay in the
Pacific Ocean experiments. TEP production in the on-deck incubation experiments
was closely related to the observed cell decay rates of Prochlorococcus sp.,
suggesting that this picocyanobacteria genus is a potential source of TEP. The
evidence to propose such potential role was derived experimentally, using natural
communities including the presence of several species and a variety of processes.
Laboratory experiments with cultures of a non-axenic strain of Prochlorococcus
marinus were then used to test TEP production by this genus. TEP concentrations
in the culture increased with increasing cell abundance during the exponential
phase, reaching the highest TEP concentration at the beginning of the stationary
phase. The average TEP concentration of 1474 +/- 226 MUg XG Eq. L-1 (mean +/- SE)
observed at the stationary phase of P. marinus cultures is comparable with the
values reported in the literature for diatom cultures, also growing in non-axenic
as well as axenic cultures. Our results identify Prochlorococcus sp. as a
possible relevant source of TEP in the oligotrophic ocean.
PMID- 28491057
TI - Identification of Genes Controlled by the Essential YycFG Two-Component System
Reveals a Role for Biofilm Modulation in Staphylococcus epidermidis.
AB - Biofilms play a crucial role in the pathogenicity of Staphylococcus epidermidis,
while little is known about whether the essential YycFG two-component signal
transduction system (TCS) is involved in biofilm formation. We used antisense RNA
(asRNA) to silence the yycFG TCS in order to study its regulatory functions in S.
epidermidis. Strain 1457 expressing asRNA yycF exhibited a significant delay (~4
5 h) in entry to log phase, which was partially complemented by overexpressing
ssaA. The expression of asRNA yycF and asRNA yycG resulted in a 68 and 50%
decrease in biofilm formation at 6 h, respectively, while they had no significant
inhibitory effect on 12 h biofilm formation. The expression of asRNA yycF led to
a ~5-fold increase in polysaccharide intercellular adhesion (PIA) production, but
it did not affect the expression of accumulation-associated protein (Aap) or the
release of extracellular DNA. Consistently, quantitative real-time PCR showed
that silencing yycF resulted in an increased transcription of biofilm-related
genes, including icaA, arlR, sarA, sarX, and sbp. An in silico search of the YycF
regulon for the conserved YycF recognition pattern and a modified motif in S.
epidermidis, along with additional gel shift and DNase I footprinting assays,
showed that arlR, sarA, sarX, and icaA are directly regulated by YycF. Our data
suggests that YycFG modulates S. epidermidis biofilm formation in an ica
dependent manner.
PMID- 28491058
TI - A Meta-Transcriptomics Survey Reveals Changes in the Microbiota of the Chinese
Mitten Crab Eriocheir sinensis Infected with Hepatopancreatic Necrosis Disease.
AB - Infection of the freshwater Chinese mitten crab Eriocheir sinensis with
hepatopancreatic necrosis disease (HPND) has been a major problem in the crab
cultivated Chinese Province of Jiangsu since 2015. To explore the etiology of
HPND, meta-transcriptomic libraries of the hepatopancreata from crabs with and
without HPND were constructed. Comparison analyses showed that there were no
statistically significant differences in viral and microsporidial communities in
the hepatopancreata of diseased and healthy crabs. Bacteroidetes, Proteobacteria,
and Firmicutes were the most dominant bacterial phyla in the hepatopancreata of
healthy crabs, with a combined prevalence of 93%. However, a decrease in
bacterial diversity and a striking shift in the microbial composition were found
in the hepatopancreata of crabs infected with HPND. Tenericutes was the most
prevalent bacterial phylum in diseased crabs (31.82%), whereas its prevalence was
low in healthy crabs (0.02%). By contrast, the prevalence of Bacteroidetes was
significantly lower in crabs with HPND (3.49%) than in crabs without HPND
(41.04%). We also found that the prevalence of Actinobacteria was higher in crabs
with HPND (16.70%) than in crabs without the disease (4.03%). The major bacterial
family within the Tenericutes phylum in crabs with HPND was detected by
polymerase chain reaction and determined to be Mycoplasmataceae. In conclusion,
there were striking changes in the microbiota of diseased and healthy crabs.
Specifically, the prevalence of bacteria belonging to Tenericutes and
Actinobacteria phyla increased, whereas the prevalence of bacteria belonging to
the Bacteroidetes phylum decreased in crabs with HPND, clearly pointing to an
association with HPND.
PMID- 28491059
TI - Elucidation of the Role of 3-Hydroxy Fatty Acids in Cryptococcus-amoeba
Interactions.
AB - We previously reported that 3-hydroxy fatty acids promoted the survival of
cryptococcal cells when acted upon by amoebae. To expand on this, the current
study sought to explain how these molecules may protect cells. Our data suggest
that 3-hydroxy fatty acids may subvert the internalization of cryptococcal cells
via suppression of the levels of a fetuin A-like amoebal protein, which may be
important for enhancing phagocytosis. Additionally, we show that an acapsular
strain (that is devoid of 3-hydroxy fatty acids) was protected against the
effects of hydrogen peroxide when exogenous 3-hydroxy fatty acids were present,
but not in the absence of 3-hydroxy fatty acids. A similar response profile was
noted when a strain with a capsule was challenged with hydrogen peroxide. We also
show that cryptococcal cells that naturally produce 3-hydroxy fatty acids were
more resistant to the effects of amoebapore (an amoeba-specific hydrolytic
enzyme), compared to cells that do not produce these molecules. Taken together,
our findings suggest that 3-hydroxy fatty acids possess an anti-phagocytic
activity that may be expressed when cells interact with macrophages. This may
allow the yeast cells to evade immuno-processing.
PMID- 28491061
TI - 4,4'-Diaponeurosporene-Producing Bacillus subtilis Increased Mouse Resistance
against Salmonella typhimurium Infection in a CD36-Dependent Manner.
AB - Deficient mucosal innate immunity is a hallmark of infectious diarrhea, such as
Salmonella typhimurium (S. typhimurium)-induced gastroenteritis. Here, we report
that oral administration of a 4,4'-diaponeurosporene-producing Bacillus subtilis
(B.s-Dia) could improve mice mucosal immunity, as showed by an increased
resistance against S. typhimurium infection. Intragastric administration of B.s
Dia for 7 days could increase the secretion of CCL20 by intestinal epithelial
cells (IECs) and then recruit more dendritic cells. Meanwhile, the number of
CD8alphaalpha+ intraepithelial lymphocytes, which play a critical role in
downregulating immune responses, was also reduced, probably as a consequence of
the decrease of IEC-derived TGFbeta. Further study showed that CD36 played a
critical role in B.s-Dia-induced immune enhancement, as blocking CD36 signal with
a specific antagonist, sulfo-N-succinimidyl oleate, led to the inability of B.s
Dia to enhance mucosal innate immunity.
PMID- 28491060
TI - Shaping of Natural Killer Cell Antitumor Activity by Ex Vivo Cultivation.
AB - Natural killer (NK) cells are a promising tool for the use in adoptive
immunotherapy, since they efficiently recognize and kill tumor cells. In this
context, ex vivo cultivation is an attractive option to increase NK cells in
numbers and to improve their antitumor potential prior to clinical applications.
Consequently, various strategies to generate NK cells for adoptive immunotherapy
have been developed. Here, we give an overview of different NK cell cultivation
approaches and their impact on shaping the NK cell antitumor activity. So far,
the cytokines interleukin (IL)-2, IL-12, IL-15, IL-18, and IL-21 are used to
culture and expand NK cells. The selection of the respective cytokine combination
is an important factor that directly affects NK cell maturation, proliferation,
survival, distribution of NK cell subpopulations, activation, and function in
terms of cytokine production and cytotoxic potential. Importantly, cytokines can
upregulate the expression of certain activating receptors on NK cells, thereby
increasing their responsiveness against tumor cells that express the
corresponding ligands. Apart from using cytokines, cocultivation with autologous
accessory non-NK cells or addition of growth-inactivated feeder cells are
approaches for NK cell cultivation with pronounced effects on NK cell activation
and expansion. Furthermore, ex vivo cultivation was reported to prime NK cells
for the killing of tumor cells that were previously resistant to NK cell attack.
In general, NK cells become frequently dysfunctional in cancer patients, for
instance, by downregulation of NK cell activating receptors, disabling them in
their antitumor response. In such scenario, ex vivo cultivation can be helpful to
arm NK cells with enhanced antitumor properties to overcome immunosuppression. In
this review, we summarize the current knowledge on NK cell modulation by
different ex vivo cultivation strategies focused on increasing NK cytotoxicity
for clinical application in malignant diseases. Moreover, we critically discuss
the technical and regulatory aspects and challenges underlying NK cell based
therapeutic approaches in the clinics.
PMID- 28491062
TI - A Kinetic Study of CD83 Reveals an Upregulation and Higher Production of sCD83 in
Lymphocytes from Pregnant Mice.
AB - For the normal development of pregnancy, a balance between immune tolerance and
defense is crucial. However, the mechanisms mediating such a balance are not
fully understood. CD83 is a transmembrane protein whose expression has been
linked to anti-inflammatory functions of T and B cells. The soluble form of CD83,
released by cleavage of the membrane-bound protein, has strong anti-inflammatory
properties and was successfully tested in different mouse models. It is assumed
that this molecule contributes to the establishment of immune tolerance.
Therefore, we postulated that the expression of CD83 is crucial for immune
tolerance during pregnancy in mice. Here, we demonstrated that the membrane-bound
form of CD83 was upregulated in T and B cells during allogeneic murine
pregnancies. An upregulation was also evident in the main splenic B cell
subtypes: marginal zone, follicular zone, and transitional B cells. We also
showed that there was an augmentation in the number of CD83+ cells toward the end
of pregnancy within splenic B and CD4+ T cells, while CD83+ dendritic cells were
reduced in spleen and inguinal lymph nodes of pregnant mice. Additionally, B
lymphocytes in late-pregnancy presented a markedly higher sensitivity to LPS in
terms of CD83 expression and sCD83 release. Progesterone induced a dosis
dependent upregulation of CD83 on T cells. Our data suggest that the regulation
of CD83 expression represents a novel pathway of fetal tolerance and protection
against inflammatory threats during pregnancy.
PMID- 28491063
TI - ISA-2011B, a Phosphatidylinositol 4-Phosphate 5-Kinase alpha Inhibitor, Impairs
CD28-Dependent Costimulatory and Pro-inflammatory Signals in Human T Lymphocytes.
AB - Phosphatidylinositol 4,5-biphosphate (PIP2) is a membrane phospholipid that
controls the activity of several proteins regulating cytoskeleton reorganization,
cytokine gene expression, T cell survival, proliferation, and differentiation.
Phosphatidylinositol 4-phosphate 5-kinases (PIP5Ks) are the main enzymes involved
in PIP2 biosynthesis by phosphorylating phosphatidylinositol 4-monophosphate
(PI4P) at the D5 position of the inositol ring. In human T lymphocytes, we
recently found that CD28 costimulatory molecule is pivotal for PIP2 turnover by
recruiting and activating PIP5Kalpha. We also found that PIP5Kalpha is the main
regulator of both CD28 costimulatory signals integrating those delivered by TCR
as well as CD28 autonomous signals regulating the expression of pro-inflammatory
genes. Given emerging studies linking alterations of PIP2 metabolism to immune
based diseases, PIP5Kalpha may represent a promising target to modulate immunity
and inflammation. Herewith, we characterized a recently discovered inhibitor of
PIP5Kalpha, ISA-2011B, for its inhibitory effects on T lymphocyte functions. We
found that the inhibition of PIP5Kalpha lipid-kinase activity by ISA-2011B
significantly impaired CD28 costimulatory signals necessary for TCR-mediated Ca2+
influx, NF-AT transcriptional activity, and IL-2 gene expression as well as CD28
autonomous signals regulating the activation of NF-kappaB and the transcription
of pro-inflammatory cytokine and chemokine genes. Moreover, our data on the
inhibitory effects of ISA-2011B on CD28-mediated upregulation of inflammatory
cytokines related to Th17 cell phenotype in type 1 diabetes patients suggest ISA
2011B as a promising anti-inflammatory drug.
PMID- 28491065
TI - OsPhyB-Mediating Novel Regulatory Pathway for Drought Tolerance in Rice Root
Identified by a Global RNA-Seq Transcriptome Analysis of Rice Genes in Response
to Water Deficiencies.
AB - Water deficiencies are one of the most serious challenges to crop productivity.
To improve our understanding of soil moisture stress, we performed RNA-Seq
analysis using roots from 4-week-old rice seedlings grown in soil that had been
subjected to drought conditions for 2-3 d. In all, 1,098 genes were up-regulated
in response to soil moisture stress for 3 d, which causes severe damage in root
development after recovery, unlikely that of 2 d. Comparison with previous
transcriptome data produced in drought condition indicated that more than 68% of
our candidate genes were not previously identified, emphasizing the novelty of
our transcriptome analysis for drought response in soil condition. We then
validated the expression patterns of two candidate genes using a promoter-GUS
reporter system in planta and monitored the stress response with novel molecular
markers. An integrating omics tool, MapMan analysis, indicated that RING box E3
ligases in the ubiquitin-proteasome pathways are significantly stimulated by
induced drought. We also analyzed the functions of 66 candidate genes that have
been functionally investigated previously, suggesting the primary roles of our
candidate genes in resistance or tolerance relating traits including drought
tolerance (29 genes) through literature searches besides diverse regulatory roles
of our candidate genes for morphological traits (15 genes) or physiological
traits (22 genes). Of these, we used a T-DNA insertional mutant of rice
phytochrome B (OsPhyB) that negatively regulates a plant's degree of tolerance to
water deficiencies through the control of total leaf area and stomatal density
based on previous finding. Unlike previous result, we found that OsPhyB represses
the activity of ascorbate peroxidase and catalase mediating reactive oxygen
species (ROS) processing machinery required for drought tolerance of roots in
soil condition, suggesting the potential significance of remaining
uncharacterized candidate genes for manipulating drought tolerance in rice.
PMID- 28491066
TI - Robust Phylogeny of Tetrastigma (Vitaceae) Based on Ten Plastid DNA Regions:
Implications for Infrageneric Classification and Seed Character Evolution.
AB - Tetrastigma (Miq.) Planch. is one of the most species-rich genera of the
economically and agronomically important grape family Vitaceae. It includes ca.
95 species widely distributed in the tropics and subtropics of Asia and
Australia. Species of Tetrastigma exhibit great diversity in both vegetative and
reproductive characters. Here we inferred a well-supported phylogeny of
Tetrastigma based on ten chloroplast DNA regions with an expanded taxon sampling
of 72 species and two varieties. Our molecular results support six major clades
within Tetrastigma and the relationships among these clades were well-resolved.
We also documented seed morphology of 44 species covering the six major clades of
the genus. Ancestral states of eight characters (seed shape, seed surface
rumination pattern, chalaza length/width ratio, chalaza position, ventral infold
position, ventral infold divergence, ventral infold depth in cross section, and
endosperm shape) were reconstructed in Mesquite and R with four models. Character
optimizations suggest that all character states have evolved multiple times
except that the irregular-shaped surface rumination has derived only once in
Tetrastigma. We evaluated the taxonomic importance of seed morphology and
identified potential morphological evidence to support each major clade. Our
comprehensive analyses of Tetrastigma shed insights into the infrageneric
classification of this morphologically diverse and ecologically important genus
in tropical and subtropical Asia.
PMID- 28491064
TI - Mitochondria-Derived Damage-Associated Molecular Patterns in Neurodegeneration.
AB - Inflammation is increasingly implicated in neurodegenerative disease pathology.
As no acquired pathogen appears to drive this inflammation, the question of what
does remains. Recent advances indicate damage-associated molecular pattern (DAMP)
molecules, which are released by injured and dying cells, can cause specific
inflammatory cascades. Inflammation, therefore, can be endogenously induced.
Mitochondrial components induce inflammatory responses in several pathological
conditions. Due to evidence such as this, a number of mitochondrial components,
including mitochondrial DNA, have been labeled as DAMP molecules. In this review,
we consider the contributions of mitochondrial-derived DAMPs to inflammation
observed in neurodegenerative diseases.
PMID- 28491067
TI - Genome-Wide Association Study Reveals the Genetic Architecture Underlying Salt
Tolerance-Related Traits in Rapeseed (Brassica napus L.).
AB - Soil salinity is a serious threat to agriculture sustainability worldwide. Salt
tolerance at the seedling stage is crucial for plant establishment and high yield
in saline soils; however, little information is available on rapeseed (Brassica
napus L.) salt tolerance. We evaluated salt tolerance in different rapeseed
accessions and conducted a genome-wide association study (GWAS) to identify salt
tolerance-related quantitative trait loci (QTL). A natural population comprising
368 B. napus cultivars and inbred lines was genotyped with a Brassica 60K
Illumina Infinium SNP array. The results revealed that 75 single-nucleotide
polymorphisms (SNPs) distributed across 14 chromosomes were associated with four
salt tolerance-related traits. These SNPs integrated into 25 QTLs that explained
4.21-9.23% of the phenotypic variation in the cultivars. Additionally, 38
possible candidate genes were identified in genomic regions associated with salt
tolerance indices. These genes fell into several functional groups that are
associated with plant salt tolerance, including transcription factors,
aquaporins, transporters, and enzymes. Thus, salt tolerance in rapeseed involves
complex molecular mechanisms. Our results provide valuable information for
studying the genetic control of salt tolerance in B. napus seedlings and may
facilitate marker-based breeding for rapeseed salt tolerance.
PMID- 28491068
TI - Phytoplasmas-The "Crouching Tiger" Threat of Australian Plant Pathology.
AB - Phytoplasmas are insect-vectored bacteria that cause disease in a wide range of
plant species. The increasing availability of molecular DNA analyses, expertise
and additional methods in recent years has led to a proliferation of discoveries
of phytoplasma-plant host associations and in the numbers of taxonomic groupings
for phytoplasmas. The widespread use of common names based on the diseases with
which they are associated, as well as separate phenetic and taxonomic systems for
classifying phytoplasmas based on variation at the 16S rRNA-encoding gene,
complicates interpretation of the literature. We explore this issue and related
trends through a focus on Australian pathosystems, providing the first
comprehensive compilation of information for this continent, covering the
phytoplasmas, host plants, vectors and diseases. Of the 33 16Sr groups reported
internationally, only groups I, II, III, X, XI and XII have been recorded in
Australia and this highlights the need for ongoing biosecurity measures to
prevent the introduction of additional pathogen groups. Many of the phytoplasmas
reported in Australia have not been sufficiently well studied to assign them to
16Sr groups so it is likely that unrecognized groups and sub-groups are present.
Wide host plant ranges are apparent among well studied phytoplasmas, with
multiple crop and non-crop species infected by some. Disease management is
further complicated by the fact that putative vectors have been identified for
few phytoplasmas, especially in Australia. Despite rapid progress in recent years
using molecular approaches, phytoplasmas remain the least well studied group of
plant pathogens, making them a "crouching tiger" disease threat.
PMID- 28491069
TI - Characterization of the Polycomb-Group Mark H3K27me3 in Unicellular Algae.
AB - Polycomb Group (PcG) proteins mediate chromatin repression in plants and animals
by catalyzing H3K27 methylation and H2AK118/119 mono-ubiquitination through the
activity of the Polycomb repressive complex 2 (PRC2) and PRC1, respectively. PcG
proteins were extensively studied in higher plants, but their function and target
genes in unicellular branches of the green lineage remain largely unknown. To
shed light on PcG function and modus operandi in a broad evolutionary context, we
demonstrate phylogenetic relationship of core PRC1 and PRC2 proteins and H3K27me3
biochemical presence in several unicellular algae of different phylogenetic
subclades. We focus then on one of the species, the model red alga
Cyanidioschizon merolae, and show that H3K27me3 occupies both, genes and
repetitive elements, and mediates the strength of repression depending on the
differential occupancy over gene bodies. Furthermore, we report that H3K27me3 in
C. merolae is enriched in telomeric and subtelomeric regions of the chromosomes
and has unique preferential binding toward intein-containing genes involved in
protein splicing. Thus, our study gives important insight for Polycomb-mediated
repression in lower eukaryotes, uncovering a previously unknown link between
H3K27me3 targets and protein splicing.
PMID- 28491071
TI - Exploring Blueberry Aroma Complexity by Chromatographic and Direct-Injection
Spectrometric Techniques.
AB - Blueberry (Vaccinium spp.) fruit consumption has increased over the last 5 years,
becoming the second most important soft fruit species after strawberry. Despite
the possible economic and sensory impact, the blueberry volatile organic compound
(VOC) composition has been poorly investigated. Thus, the great impact of the
aroma on fruit marketability stimulates the need to step forward in the
understanding of this quality trait. Beside the strong effect of ripening,
blueberry aroma profile also varies due to the broad genetic differences among
Vaccinium species that have been differently introgressed in modern commercial
cultivars through breeding activity. In the present study, divided into two
different activities, the complexity of blueberry aroma was explored by an
exhaustive untargeted VOC analysis, performed by two complementary methods: SPME
GC-MS (solid phase microextraction- gas chromatography-mass spectrometry) and PTR
ToF-MS (proton transfer reaction-time of flight-mass spectrometry). The first
experiment was aimed at determining the VOC modifications during blueberry
ripening for five commercially representative cultivars ("Biloxi," "Brigitta
Blue," "Centurion," "Chandler," and "Ozark Blue") harvested at four ripening
stages (green, pink, ripe, and over-ripe) to outline VOCs dynamic during fruit
development. The objective of the second experiment was to confirm the analytical
capability of PTR-ToF-MS to profile blueberry genotypes and to identify the most
characterizing VOCs. In this case, 11 accessions belonging to different Vaccinium
species were employed: V. corymbosum L. ("Brigitta," "Chandler," "Liberty," and
"Ozark Blue"), V. virgatum Aiton ("Centurion," "Powder Blue," and "Sky Blue"), V.
myrtillus L. (three wild genotypes of different mountain locations), and one
accession of V. cylindraceum Smith. This comprehensive characterization of
blueberry aroma allowed the identification of a wide pull of VOCs, for the most
aldehydes, alcohols, terpenoids, and esters that can be used as putative
biomarkers to rapidly evaluate the blueberry aroma variations related to ripening
and/or senescence as well as to genetic background differences. Moreover, the
obtained results demonstrated the complementarity between chromatographic and
direct-injection mass spectrometric techniques to study the blueberry aroma.
PMID- 28491070
TI - Ascorbic Acid-A Potential Oxidant Scavenger and Its Role in Plant Development and
Abiotic Stress Tolerance.
AB - Over-production of reactive oxygen species (ROS) in plants under stress
conditions is a common phenomenon. Plants tend to counter this problem through
their ability to synthesize ROS neutralizing substances including non-enzymatic
and enzymatic antioxidants. In this context, ascorbic acid (AsA) is one of the
universal non-enzymatic antioxidants having substantial potential of not only
scavenging ROS, but also modulating a number of fundamental functions in plants
both under stress and non-stress conditions. In the present review, the role of
AsA, its biosynthesis, and cross-talk with different hormones have been discussed
comprehensively. Furthermore, the possible involvement of AsA-hormone crosstalk
in the regulation of several key physiological and biochemical processes like
seed germination, photosynthesis, floral induction, fruit expansion, ROS
regulation and senescence has also been described. A simplified and schematic AsA
biosynthetic pathway has been drawn, which reflects key intermediates involved
therein. This could pave the way for future research to elucidate the modulation
of plant AsA biosynthesis and subsequent responses to environmental stresses.
Apart from discussing the role of different ascorbate peroxidase isoforms, the
comparative role of two key enzymes, ascorbate peroxidase (APX) and ascorbate
oxidase (AO) involved in AsA metabolism in plant cell apoplast is also discussed
particularly focusing on oxidative stress perception and amplification. Limited
progress has been made so far in terms of developing transgenics which could over
produce AsA. The prospects of generation of transgenics overexpressing AsA
related genes and exogenous application of AsA have been discussed at length in
the review.
PMID- 28491072
TI - ThNAC13, a NAC Transcription Factor from Tamarix hispida, Confers Salt and
Osmotic Stress Tolerance to Transgenic Tamarix and Arabidopsis.
AB - NAC (NAM, ATAF1/2, and CUC2) proteins play critical roles in many plant
biological processes and environmental stress. However, NAC proteins from Tamarix
hispida have not been functionally characterized. Here, we studied a NAC gene
from T. hispida, ThNAC13, in response to salt and osmotic stresses. ThNAC13 is a
nuclear protein with a C-terminal transactivation domain. ThNAC13 can bind to NAC
recognized sites and calmodulin-binding NAC (CBNAC) binding element.
Overexpression of ThNAC13 in Arabidopsis improved seed germination rate and
increased root growth and fresh weight gain under salt or osmotic stress.
Transgenic T. hispida plants transiently overexpressing ThNAC13 and with RNAi
silenced ThNAC13 were generated for gain- and loss-of-function experiments.
Following exposure to salt or osmotic stress, overexpression of ThNAC13 induced
superoxide dismutase (SOD) and peroxidase (POD) activities, chlorophyll and
proline contents; decreased the reactive oxygen species (ROS) and malondialdehyde
levels; and reduced electrolyte leakage rates in both transgenic Tamarix and
Arabidopsis plants. In contrast, RNAi-silenced ThNAC13 showed the opposite
results in transgenic Tamarix. Furthermore, ThNAC13 induced the expression of
SODs and PODs in transgenic Arabidopsis. These results suggest that ThNAC13
improves salt and osmotic tolerance by enhancing the ROS-scavenging capability
and adjusting osmotic potential.
PMID- 28491074
TI - Editorial: Plant Competition in a Changing World.
PMID- 28491073
TI - Regulation of Translation by TOR, eIF4E and eIF2alpha in Plants: Current
Knowledge, Challenges and Future Perspectives.
AB - An important step in eukaryotic gene expression is the synthesis of proteins from
mRNA, a process classically divided into three stages, initiation, elongation,
and termination. Translation is a precisely regulated and conserved process in
eukaryotes. The presence of plant-specific translation initiation factors and the
lack of well-known translational regulatory pathways in this kingdom nonetheless
indicate how a globally conserved process can diversify among organisms. The
control of protein translation is a central aspect of plant development and
adaptation to environmental stress, but the mechanisms are still poorly
understood. Here we discuss current knowledge of the principal mechanisms that
regulate translation initiation in plants, with special attention to the
singularities of this eukaryotic kingdom. In addition, we highlight the major
recent breakthroughs in the field and the main challenges to address in the
coming years.
PMID- 28491075
TI - Saturation Mapping of a Major Effect QTL for Stripe Rust Resistance on Wheat
Chromosome 2B in Cultivar Napo 63 Using SNP Genotyping Arrays.
AB - Stripe rust or yellow rust (YR), caused by Puccinia striiformis f. sp. tritici
(Pst), is one of the most important diseases of wheat (Triticum aestivum L.).
Widespread deployment of resistant cultivars is the best means of achieving
durable disease control. The red grain, spring wheat cultivar Napo 63 produced by
CIMMYT in the 1960s shows a high level of adult-plant resistance to stripe rust
in the field. To elucidate the genetic basis of resistance in this cultivar we
evaluated 224 F2:3 lines and 175 F2:6 recombinant inbred lines (RILs) derived
from a cross between Napo 63 and the Pst-susceptible line Avocet S. The maximum
disease severity (MDS) data of F2:3 lines and the relative area under the disease
progress curve (rAUDPC) data of RILs were collected during the 2014-2015 and 2015
2016 wheat growing seasons, respectively. Combined bulked segregant analysis and
90K single nucleotide polymorphism (SNP) arrays placed 275 of 511 polymorphic
SNPs on chromosome 2B. Sixty four KASP markers selected from the 275 SNPs and 76
SSR markers on 2B were used to identify a chromosome region associated with rust
response. A major effect QTL, named Qyrnap.nwafu-2BS, was identified by inclusive
composite interval mapping and was preliminarily mapped to a 5.46 cM interval
flanked by KASP markers 90K-AN34 and 90K-AN36 in chromosome 2BS. Fourteen KASP
markers more closely linked to the locus were developed following a 660K SNP
array analysis. The QTL region was finally narrowed to a 0.9 cM interval flanked
by KASP markers 660K-AN21 and 660K-AN57 in bin region 2BS-1-0.53. The resistance
of Napo 63 was stable across all environments, and as a QTL, explained an average
66.1% of the phenotypic variance in MDS of F2:3 lines and 55.7% of the phenotypic
variance in rAUDPC of F5:6 RILs. The short genetic interval and flanking KASP
markers developed in the study will facilitate marker-assisted selection, gene
pyramiding, and eventual positional cloning of Qyrnap.nwafu-2BS.
PMID- 28491077
TI - How Should Plant Resistance to Herbivores Be Measured?
PMID- 28491076
TI - A Proteomic Approach Suggests Unbalanced Proteasome Functioning Induced by the
Growth-Promoting Bacterium Kosakonia radicincitans in Arabidopsis.
AB - Endophytic plant growth-promoting bacteria have significant impact on the plant
physiology and understanding this interaction at the molecular level is of
particular interest to support crop productivity and sustainable production
systems. We used a proteomics approach to investigate the molecular mechanisms
underlying plant growth promotion in the interaction of Kosakonia radicincitans
DSM 16656 with Arabidopsis thaliana. Four weeks after the inoculation, the
proteome of roots from inoculated and control plants was compared using two
dimensional gel electrophoresis and differentially abundant protein spots were
identified by liquid chromatography tandem mass spectrometry. Twelve protein
spots were responsive to the inoculation, with the majority of them being related
to cellular stress reactions. The protein expression of 20S proteasome alpha-3
subunit was increased by the presence of K. radicincitans. Determination of
proteasome activity and immuno blotting analysis for ubiquitinated proteins
revealed that endophytic colonization interferes with ubiquitin-dependent protein
degradation. Inoculation of rpn12a, defective in a 26S proteasome regulatory
particle, enhanced the growth-promoting effect. This indicates that the plant
proteasome, besides being a known target for plant pathogenic bacteria, is
involved in the establishment of beneficial interactions of microorganisms with
plants.
PMID- 28491078
TI - The Importance of Being on Time: Regulatory Networks Controlling Photoperiodic
Flowering in Cereals.
AB - Flowering is the result of the coordination between genetic information and
environmental cues. Gene regulatory networks have evolved in plants in order to
measure diurnal and seasonal variation of day length (or photoperiod), thus
aligning the reproductive phase with the most favorable season of the year. The
capacity of plants to discriminate distinct photoperiods classifies them into
long and short day species, depending on the conditions that induce flowering.
Plants of tropical origin and adapted to short day lengths include rice, maize,
and sorghum, whereas wheat and barley were originally domesticated in the Fertile
Crescent and are considered long day species. In these and other crops, day
length measurement mechanisms have been artificially modified during
domestication and breeding to adapt plants to novel areas, to the extent that a
wide diversity of responses exists within any given species. Notwithstanding the
ample natural and artificial variation of day length responses, some of the basic
molecular elements governing photoperiodic flowering are widely conserved.
However, as our understanding of the underlying mechanisms improves, it becomes
evident that specific regulators exist in many lineages that are not shared by
others, while apparently conserved components can be recruited to novel functions
during evolution.
PMID- 28491079
TI - Similar Morphologies but Different Origins: Hybrid Status of Two More Semi
creeping Taxa of Melastoma.
AB - Inferring the origins of hybrid taxa based on morphology alone is difficult
because morphologically similar hybrids can arise from hybridization between
different populations of the same parental species or be produced by
hybridization of different parental species. In this study, we investigated the
origins of two semi-creeping taxa in Melastoma, which are morphologically similar
to a natural hybrid, M. intermedium, by sequencing a chloroplast intergenic
spacer, nuclear ribosomal internal transcribed spacer and two low-copy nuclear
genes (tpi and cam) in these taxa and their putative parental species. Our
sequence analysis provides compelling evidence for the hybrid status of the two
semi-creeping taxa: one originating from hybridization between M. dodecandrum and
M. malabathricum, and the other between M. dodecandrum and M. normale. The
origins of these hybrids are therefore clearly different from M. intermedium, and
morphological similarity for the three hybrids is most likely due to their
origins from hybridization between the same creeping species M. dodecandrum and a
different erect species in each of the three cases. We also observed low rate of
introgression from M. normale to M. dodecandrum, and genetic exchange between
them may transfer adaptive traits to M. dodecandrum. Rare occurrence of these two
hybrids may be due to small range overlaps between parental species in one case,
and different flowering periods between parental species in the other.
PMID- 28491080
TI - Corrigendum: Making Plants Break a Sweat: the Structure, Function, and Evolution
of Plant Salt Glands.
AB - [This corrects the article on p. 406 in vol. 8, PMID: 28400779.].
PMID- 28491081
TI - Safety and efficacy of transradial coronary angiography and intervention in
patients older than 80 years: from the Korean Transradial Intervention
Prospective Registry.
AB - BACKGROUND: Radial artery access for coronary procedures is a safe and beneficial
technique. However, elderly patients have been considered as a higher risk group
of access site related complications compared to younger patients. This study was
conducted to investigate the feasibility and safety of transradial coronary
angiography or intervention in the elderly. METHODS: A total of 6132 patients
from Korean Transradial Intervention Prospective Registry at 20 centers were
analyzed. Patients were divided into the non-elderly group (n = 5667) and the
elderly (>= 80 years) group (n = 465). Using propensity score matching, the
elderly group (n = 465) was compared with one-to-one matched the non-elderly
group (n = 465). RESULTS: After propensity score matching, mean age was 64.3 +/-
10.3 years in the non-elderly group and 83.5 +/- 3.3 years in the elderly group.
There was no difference of procedural characteristics, procedural and
fluoroscopic times. Access site cross-over rate was not different between the non
elderly group and elderly group (7.5% vs. 6.2%, P = 0.074). Bleeding
complications occurred similarly in two groups (2.6% of the non-elderly group vs.
1.9% of the elderly group, P = 0.660). Access site complications were 1.9% of the
non-elderly group and 0.9% of the elderly group (P = 0.263). Both of in hospital
death and cardiovascular death for one year were also similar between two groups.
CONCLUSIONS: Transradial angiography or intervention was safe and feasible in
elderly patients. Complication rates and clinical outcomes in elderly patients
were comparable with those in non-elderly patients.
PMID- 28491082
TI - Altered serum level of cartilage oligomeric matrix protein and its association
with coronary calcification in patients with coronary heart disease.
AB - BACKGROUND: Cartilage oligomeric matrix protein (COMP) is mainly found in the
skeletal system and vascular smooth muscle cells. Recent researches showed that
it had a protective function on blood vessels and could also inhibit vascular
calcification. We investigated the serum COMPs in coronary heart disease (CHD)
patients, and the relationship between serum COMP and the calcification of
coronary artery. METHODS: A total of 233 consecutive chest pain patients who
first underwent coronary angiography followed by multi-slice computed tomography
(MSCT) within six months were recruited and divided into two groups according to
the coronary angiography luminal diameter narrowing percentages: CHD group
(diameter narrowing >= 50%, n = 194) and control group (diameter narrowing < 50%,
n = 39). The Gensini score, Syntax score and coronary artery calcium score (CACs)
were calculated. The serum COMP level was determined using ELISA. RESULTS: The
levels of COMP were significantly higher in the CHD group than in the control
group 155.7 (124.5-194.5) ng/mL vs. 128.4 (113.0-159.9) ng/mL, P = 0.019. There
were no correlation between COMP, Gensini score, Syntax score, severity of
coronary stenosis and the number of coronary artery with stenosis > 50%. The
serum COMP was correlated with age (r = 0.294, P < 0.001), fasting glucose (r =
0.163, P = 0.015), HbA1c (r = 0.194, P = 0.015) and CACs (r = 0.137, P = 0.037).
Stepwise linear regression analysis showed that COMP level and age were
independent predictors of CACs in the CHD patients (beta = 0.402, t = 2.612, P =
0.015; beta = 0.472, t = 3.077, P = 0.005). Performance of COMP for predicting
CHD was shown as area under curve (AUC): 0.632, 95% CI: 0.549-0.715 and upper
tertile CACs was AUC: 0.602, 95% CI: 0.526-0.678 in receiver operating
characteristic (ROC) curve analysis. CONCLUSION: Calcification of coronary artery
was an independent predictor of serum COMPs.
PMID- 28491083
TI - Comparison of the performance of the CRUSADE, ACUITY-HORIZONS, and ACTION
bleeding scores in ACS patients undergoing PCI: insights from a cohort of 4939
patients in China.
AB - BACKGROUND: The CRUSADE, ACTION and ACUITY-HORIZONS scores are commonly used for
predicting in-hospital major bleeding events in patients with acute coronary
syndrome (ACS), but the homogeneous nature of these models' population limits
simple extrapolation to other local population. We aimed to compare the
performance of the three risk models in Chinese patients. METHODS: We evaluated
the performance of the three predicting scores for predicting in-hospital major
bleeding events defined by thrombolysis in myocardial infarction (TIMI) serious
(major and minor) episodes, in a cohort of Chinese ACS patients with either non
ST-elevation ACS (NSTE-ACS) or ST-elevation myocardial infarction (STEMI).
Calibration and discrimination of the three risk models were evaluated by the
Hosmer-Lemeshow test and C-statistic, respectively. We compared the predictive
accuracy of the risk scores by the Delong non-parametric test. RESULTS: TIMI
serious bleeding rate was 1.1% overall (1.9% and 0.86% for STEMI and NSTE-ACS,
respectively). The CRUSADE, ACTION and ACUTIY-HORIZONS scores showed an adequate
discriminatory capacity for major bleeding: in overall patients, the C-statistic
was 0.80, 0.77, and 0.70, respectively; in NSTE-ACS patients, the C-statistic was
0.73, 0.72, and 0.64, respectively; in STEMI patients, the C-statistic was 0.91,
0.92, and 0.75, respectively. The C-statistic for the ACUITY-HORIZONS model was
significantly lower than those of the CRUSADE and ACTION scores for the
prediction of TIMI serious bleeding in overall patients (compared with CRUSADE, z
= 3.83, P = 0.02; compared with ACTION, z = 3.51, P = 0.03); in NSTE-ACS patients
(compared with CRUSADE, z = 2.37, P = 0.01; compared with ACTION, z = 2.11, P =
0.04), and in STEMI patients (compared with CRUSADE, z = 2.6.77, P = 0.02;
compared with ACTION, z = 7.91, P = 0.002). No differences were observed when the
CRUSADE and ACTION models were compared to each other, regardless of overall
patients (z = 0.68, P = 0.31) and both of ACS types (NSTE-ACS, z = 0.52, P =
0.60), and STEMI patients (z = 0.36, P = 0.74). However, the three risk scores
all overestimated the absolute major bleeding risk in each risk stratification in
our study. For example, the predicted rate of CRUSADE score at high risk
stratification was 11.9% vs. an actual rate of 5.3%. CONCLUSIONS: The CRUSADE and
ACTION scores had a greater calibration and discrimination for in-hospital major
bleeding compared with the ACUITY-HORIZONS score in Chinese patients with ACS
undergoing PCI. However, they all overestimated the bleeding risk rate for
Chinese populations. Calibration of these risk scores would be useful for the
generalization in Chinese populations.
PMID- 28491084
TI - The impact of optimal medical therapy at discharge on mortality in patients with
coronary artery disease.
AB - OBJECTIVE: To analyze the current usage of optimal medical therapy (OMT),
influencing factors, and the predictive value of OMT for all-cause mortality in
coronary artery disease (CAD) patients with different subgroups. METHODS: A total
of 3176 CAD patients confirmed by coronary angiography were included. OMT was
defined as the combination of anti-platelet drugs, statins, beta blockers, and
angiotensin converting enzyme inhibitors or angiotensin receptor blockers.
Factors for OMT and its prognostic value were analyzed in CAD patients across
different subgroups. RESULTS: Out of 3176 patients, only 39.8% (n = 1265) were on
OMT at discharge. Factors associated with OMT at discharge were pre-admission OMT
and discharge department. All-cause mortality occurred in 6.8% (n = 217) of
patients. Multivariate analyses indicated that OMT was significantly associated
with reduced all-cause mortality (HR: 0.65, 95% CI: 0.45-0.95; P = 0.025). Sub
group analyses indicate that male acute coronary syndrome (ACS) patients were
more likely to receive survival benefits with OMT at discharge. The positive
impact of OMT at discharge was more apparent after 24 months, regardless of
revascularization therapy. Four-drug combination of OMT was superior to 3-drug
combination therapy in ACS patients but not in stable patients. CONCLUSIONS: OMT
was associated with significant improvement in survival in patients with CAD. The
positive impact of OMT was distinct in the CAD patients with different
characteristics.
PMID- 28491085
TI - Stenting versus non-stenting treatment of intermediate stenosis culprit lesion in
acute ST-segment elevation myocardial infarction: a multicenter randomized
clinical trial.
AB - BACKGROUND: The benefit/risk ratio of stenting in acute ST-segment elevation
myocardial infarction (STEMI) patients with single vessel intermediate stenosis
culprit lesions merits further study, therefore the subject of the present study.
METHODS AND RESULTS: It was a prospective, multicenter, randomized controlled
trial. Between April 2012 and July 2015, 399 acute STEMI patients with single
vessel disease and intermediate (40%-70%) stenosis of the culprit lesion before
or after aspiration thrombectomy and/or intracoronary tirofiban (15 ug/kg) were
enrolled and were randomly assigned (1: 1) to stenting group (n = 201) and non
stenting group (n = 198). In stenting group, patients received pharmacologic
therapy plus standard percutaneous coronary intervention (PCI) with stent
implantation. In non-stenting group, patients received pharmacologic therapy and
PCI (thrombectomy), but without dilatation or stenting. Primary endpoint was 12
month rate of major adverse cardiac and cerebrovascular events (MACCE), a
composite of cardiac death, non-fatal myocardial infarction (MI), repeat
revascularization and stroke. Secondary endpoints were 12-month rates of all
cause death, ischemia driven admission and bleeding complication. Median follow
up time was 12.4 +/- 3.1 months. At 12 months, MACCE occurred in 8.0% of the
patients in stenting group, as compared with 15.2% in the non-stenting group
(adjusted HR: 0.42, 95% CI: 0.19-0.89, P = 0.02). The stenting group had lower
non-fatal MI rate than non-stenting group, (1.5% vs. 5.5%, P = 0.03). The two
groups shared similar cardiac death, repeat revascularization, stroke, all cause
death, ischemia driven readmission and bleeding rates at 12 months. CONCLUSIONS:
Stent implantation had better efficacy and safety in reducing MACCE risks among
acute STEMI patients with single vessel intermediate stenosis culprit lesions.
PMID- 28491086
TI - Left univentricular pacing for cardiac resynchronization therapy using rate
adaptive atrioventricular delay.
AB - OBJECTIVE: To evaluate left univentricular (LUV) pacing for cardiac
resynchronization therapy (CRT) using a rate-adaptive atrioventricular delay
(RAAVD) algorithm to track physiological atrioventricular delay (AVD). METHODS: A
total of 72 patients with congestive heart failure (CHF) were randomized to RAAVD
LUV pacing versus standard biventricular (BiV) pacing in a 1: 1 ratio.
Echocardiography was used to optimize AVD for both groups. The effects of
sequential BiV pacing and LUV pacing with optimized A-V (right atrio-LV) delay
using an RAAVD algorithm were compared. The standard deviation (SD) of the S/R
ratio in lead V1 at five heart rate (HR) segments (RS/R-SD5), defined as the
"tracking index," was used to evaluate the accuracy of the RAAVD algorithm for
tracking physiological AVD. RESULTS: The QRS complex duration (132 +/- 9.8 vs.
138 +/- 10 ms, P < 0.05), the time required for optimization (21 +/- 5 vs. 50 +/-
8 min, P < 0.001), the mitral regurgitant area (1.9 +/- 1.1 vs. 2.5 +/- 1.3 cm2,
P < 0.05), the interventricular mechanical delay time (60.7 +/- 13.3 ms vs. 68.3
+/- 14.2 ms, P < 0.05), and the average annual cost (13,200 +/- 1000 vs. 21,600
+/- 2000 RMB, P < 0.001) in the RAAVD LUV pacing group were significantly less
than those in the standard BiV pacing group. The aortic valve velocity-time
integral in the RAAVD LUV pacing group was greater than that in the standard BiV
pacing group (22.7 +/- 2.2 vs. 21.4 +/- 2.1 cm, P < 0.05). The RS/R-SD5 was 4.08
+/- 1.91 in the RAAVD LUV pacing group, and was significantly negatively
correlated with improved left ventricular ejection fraction (LVEF) (DeltaLVEF,
Pearson's r = -0.427, P = 0.009), and positively correlated with New York Heart
Association class (Spearman's r = 0.348, P = 0.037). CONCLUSIONS: RAAVD LUV
pacing is as effective as standard BiV pacing, can be more physiological than
standard BiV pacing, and can decrease the average annual cost of CRT.
PMID- 28491087
TI - Neutrophil-to-lymphocyte ratio compared to N-terminal pro-brain natriuretic
peptide as a prognostic marker of adverse events in elderly patients with chronic
heart failure.
AB - BACKGROUND: The neutrophil-to-lymphocyte (N/L) ratio has been associated with
poor prognosis in patients with heart failure, but it has not been compared with
N-terminal pro-brain natriuretic peptide (NT-proBNP) in elderly patients with
chronic heart failure (CHF). We sought to make this comparison. METHODS: A total
of 1355 elderly patients with CHF were analyzed. A multivariate logistic
regression model was used to analyze the variables associated with atrial
fibrillation (AF). Cox regression analysis was used to assess the multivariable
relationship between the N/L ratio, NT-proBNP level, and subsequent major
cardiovascular events (MCE). RESULTS: In the multiple logistic regression
analysis, the N/L ratio was demonstrated as a risk factor for AF in elderly
patients with CHF [odds ratio (OR): 1.079, 95% confidence interval (CI): 1.027
1.134, P = 0.003]. The median follow-up period was 18 months. In a multivariable
model using tertiles of both variables, the highest tertile of the N/L ratio was
significantly associated with MCE [hazard ratio (HR): 1.407, 95% CI: 1.098-1.802,
P = 0.007] compared with the lowest tertile. Similarly, the highest NT-proBNP
tertile was also significantly associated with MCE (HR: 1.461, 95% CI: 1.104
1.934, P = 0.008). CONCLUSIONS: In elderly patients with CHF, the N/L ratio is
one of the important risk factors for AF and it is an inexpensive and readily
available marker with similar independent prognostic power to NT-proBNP. The risk
of MCE increases 1.407-fold when the N/L ratio is elevated to the highest
tertile.
PMID- 28491089
TI - Successful treatment of intracardiac air embolism using intracardiac catheter
aspiration.
PMID- 28491090
TI - Recurrent acute myocardial infarction and atrial fibrillation.
PMID- 28491088
TI - Novel biomarkers for cardiovascular risk prediction.
AB - Cardiovascular disease (CVD) is the leading cause of death and disability
worldwide. The primary prevention of CVD is dependent upon the ability to
identify high-risk individuals long before the development of overt events. This
highlights the need for accurate risk stratification. An increasing number of
novel biomarkers have been identified to predict cardiovascular events.
Biomarkers play a critical role in the definition, prognostication, and decision
making regarding the management of cardiovascular events. This review focuses on
a variety of promising biomarkers that provide diagnostic and prognostic
information. The myocardial tissue-specific biomarker cardiac troponin, high
sensitivity assays for cardiac troponin, and heart-type fatty acid binding
proteinall help diagnose myocardial infarction (MI) in the early hours following
symptoms. Inflammatory markers such as growth differentiation factor-15, high
sensitivity C-reactive protein, fibrinogen, and uric acid predict MI and death.
Pregnancy-associated plasma protein A, myeloperoxidase, and matrix
metalloproteinases predict the risk of acute coronary syndrome. Lipoprotein
associated phospholipase A2 and secretory phospholipase A2 predict incident and
recurrent cardiovascular events. Finally, elevated natriuretic peptides, ST2,
endothelin-1, mid-regional-pro-adrenomedullin, copeptin, and galectin-3 have all
been well validated to predict death and heart failure following a MI and provide
risk stratification information for heart failure. Rapidly developing new areas,
such as assessment of micro-RNA, are also explored. All the biomarkers reflect
different aspects of the development of atherosclerosis.
PMID- 28491091
TI - Identification of Functionally Interconnected Neurons Using Factor Analysis.
AB - The advances in electrophysiological methods have allowed registering the joint
activity of single neurons. Thus, studies on functional dynamics of complex
valued neural networks and its information processing mechanism have been
conducted. Particularly, the methods for identifying neuronal interconnections
are in increasing demand in the area of neurosciences. Here, we proposed a factor
analysis to identify functional interconnections among neurons via spike trains.
This method was evaluated using simulations of neural discharges from different
interconnections schemes. The results have revealed that the proposed method not
only allows detecting neural interconnections but will also allow detecting the
presence of presynaptic neurons without the need of the recording of them.
PMID- 28491092
TI - Can Transabdominal Scan Predict a Short Cervix by Transvaginal Scan?
AB - Background. To determine whether transabdominal screening can be used to screen
women with short cervix on transvaginal scan. Methods. The study was done between
18 and 20 weeks of gestation. Transabdominal scan was done and cervical length
was measured. Transvaginal scan was also done and cervical length was measured.
An attempt was made to find out whether transabdominal scan be used to predict a
cervical length of 25 mm by transvaginal scan. Results. In our study the cut-off
for transabdominal scan for detecting a short cervix of 25 mm by transvaginal
scan was 29 mm. A transabdominal cervical length of 29 mm could predict a short
cervix of 25 mm by transvaginal scan by 100% sensitivity and 92.4% sensitivity.
Conclusion. A cut-off of 29 mm by transabdominal scan is very accurate in
predicting a short cervix of 25 mm by transvaginal scan.
PMID- 28491093
TI - Therapeutic Effect and Location of GFP-Labeled Placental Mesenchymal Stem Cells
on Hepatic Fibrosis in Rats.
AB - Background. Liver fibrosis is a chronic progressive liver disease, but no
established effective treatment exists except for liver transplantation. The
present study was designed to investigate the effect of human placenta
mesenchymal stem cells (hPMSCs) expressing green fluorescent protein (GFP) on
carbon tetrachloride- (CCl4-) induced liver fibrosis in rats. Methods. Liver
fibrosis was induced by subcutaneous injection with CCl4; hPMSCs were directly
transplanted into rats through the caudal vein. The therapeutic efficacy of
hPMSCs on liver fibrosis was measured by liver function tests, liver
elastography, histopathology, Masson's trichrome and Sirius red staining, and
immunohistochemical studies. The expression levels of fibrotic markers,
transforming growth factor beta1 (TGF-beta1) and alpha-smooth muscle actin (alpha
SMA), were assessed using real-time polymerase chain reaction. Results. We
demonstrated that liver fibrosis was significantly dampened in the hPMSC
transplantation group according to the Laennec fibrosis scoring system and
histological data. The Sirius red-stained collagen area and the elastography
score were significantly reduced in the hPMSC-treated group. Meanwhile, hPMSC
administration significantly decreased TGF-beta1 and alpha-SMA expression and
enhanced liver functions in CCl4-induced fibrotic rats. Conclusion. This study
indicates that transplantation of hPMSCs could repair liver fibrosis induced by
CCl4 in rats, which may serve as a valuable therapeutic approach to treat liver
diseases.
PMID- 28491094
TI - Immunoprofiling of Adult-Derived Human Liver Stem/Progenitor Cells: Impact of
Hepatogenic Differentiation and Inflammation.
AB - Adult-derived human liver stem/progenitor cells (ADHLSCs) are, nowadays,
developed as therapeutic medicinal product for the treatment of liver defects. In
this study, the impact of hepatogenic differentiation and inflammation priming on
the ADHLSCs' immune profile was assessed in vitro and compared to that of mature
hepatocytes. The constitutive immunological profile of ADHLSCs was greatly
different from that of hepatocytes. Differences in the expression of the stromal
markers CD90 and CD105, adhesion molecules CD44 and CD49e, immunoregulatory
molecules CD73 and HO-1, and NK ligands CD112 and CD155 were noted. While they
globally preserved their immunological profile in comparison to undifferentiated
counterparts, differentiated ADHLSCs showed a significant downregulation of CD200
expression as in hepatocytes. This was mainly induced by signals issued from EGF
and OSM. On the other hand, the impact of inflammation was quite similar for all
studied cell populations with an increased expression level of CD54 and CD106 and
induction of that of CD40 and CD274. In conclusion, our immune profiling study
suggests CD200 as a key factor in regulating the immunobiology of differentiated
ADHLSCs. A better understanding of the molecular and physiological events related
to such marker could help in designing the optimal conditions for an efficient
therapeutic use of ADHLSCs.
PMID- 28491095
TI - Angelica Sinensis Polysaccharide Prevents Hematopoietic Stem Cells Senescence in
D-Galactose-Induced Aging Mouse Model.
AB - Age-related regression in hematopoietic stem/progenitor cells (HSC/HPCs) limits
replenishment of the blood and immune system and hence contributes to
hematopoietic diseases and declined immunity. In this study, we employed D-gal
induced aging mouse model and observed the antiaging effects of Angelica Sinensis
Polysaccharide (ASP), a major active ingredient in dong quai (Chinese Angelica
Sinensis), on the Sca-1+ HSC/HPCs in vivo. ASP treatment prevents HSC/HPCs
senescence with decreased AGEs levels in the serum, reduced SA-beta-Gal positive
cells, and promoted CFU-Mix formation in the D-gal administrated mouse. We
further found that multiple mechanisms were involved: (1) ASP treatment prevented
oxidative damage as total antioxidant capacity was increased and levels of
reactive oxygen species (ROS), 8-OHdG, and 4-HNE were declined, (2) ASP reduced
the expression of gamma-H2A.X which is a DNA double strand breaks (DSBs) marker
and decreased the subsequent ectopic expressions of effectors in p16Ink4a-RB and
p19Arf-p21Cip1/Waf senescent pathways, and (3) ASP inhibited the excessive
activation of Wnt/beta-catenin signaling in aged HSC/HPCs, as the expressions of
beta-catenin, phospho-GSK-3beta, and TCF-4 were decreased, and the cyto-nuclear
translocation of beta-catenin was inhibited. Moreover, compared with the positive
control of Vitamin E, ASP exhibited a better antiaging effect and a weaker
antioxidation ability, suggesting a novel protective role of ASP in the
hematopoietic system.
PMID- 28491096
TI - Cardiovascular Regeneration: Biology and Therapy.
PMID- 28491097
TI - Wnt5a Signaling in Normal and Cancer Stem Cells.
AB - Wnt5a is involved in activating several noncanonical Wnt signaling pathways,
which can inhibit or activate canonical Wnt/beta-catenin signaling pathway in a
receptor context-dependent manner. Wnt5a signaling is critical for regulating
normal developmental processes, including stem cell self-renewal, proliferation,
differentiation, migration, adhesion, and polarity. Moreover, the aberrant
activation or inhibition of Wnt5a signaling is emerging as an important event in
cancer progression, exerting both oncogenic and tumor suppressive effects. Recent
studies show the involvement of Wnt5a signaling in regulating normal and cancer
stem cell self-renewal, cancer cell proliferation, migration, and invasion. In
this article, we review recent findings regarding the molecular mechanisms and
roles of Wnt5a signaling in stem cells in embryogenesis and in the normal or
neoplastic breast or ovary, highlighting that Wnt5a may have different effects on
target cells depending on the surface receptors expressed by the target cell.
PMID- 28491098
TI - Epigenetic Manipulation Facilitates the Generation of Skeletal Muscle Cells from
Pluripotent Stem Cells.
AB - Human pluripotent stem cells (hPSCs) have the capacity to differentiate into
essentially all cell types in the body. Such differentiation can be directed to
specific cell types by appropriate cell culture conditions or overexpressing
lineage-defining transcription factors (TFs). Especially, for the activation of
myogenic program, early studies have shown the effectiveness of enforced
expression of TFs associated with myogenic differentiation, such as PAX7 and
MYOD1. However, the efficiency of direct differentiation was rather low, most
likely due to chromatin features unique to hPSCs, which hinder the access of TFs
to genes involved in muscle differentiation. Indeed, recent studies have
demonstrated that ectopic expression of epigenetic-modifying factors such as a
histone demethylase and an ATP-dependent remodeling factor significantly enhances
myogenic differentiation from hPSCs. In this article, we review the recent
progress for in vitro generation of skeletal muscles from hPSCs through forced
epigenetic and transcriptional manipulation.
PMID- 28491099
TI - Induction of Pluripotent Stem Cells from a Manifesting Carrier of Duchenne
Muscular Dystrophy and Characterization of Their X-Inactivation Status.
AB - Three to eight percent of female carriers of Duchenne muscular dystrophy (DMD)
develop dystrophic symptoms ranging from mild muscle weakness to a rapidly
progressive DMD-like muscular dystrophy due to skewed inactivation of X
chromosomes during early development. Here, we generated human induced
pluripotent stem cells (hiPSCs) from a manifesting female carrier using
retroviral or Sendai viral (SeV) vectors and determined their X-inactivation
status. Although manifesting carrier-derived iPS cells showed normal expression
of human embryonic stem cell markers and formed well-differentiated teratomas in
vivo, many hiPS clones showed bi-allelic expression of the androgen receptor (AR)
gene and loss of X-inactivation-specific transcript and trimethyl-histone H3
(Lys27) signals on X chromosomes, suggesting that both X chromosomes of the hiPS
cells are in an active state. Importantly, normal dystrophin was expressed in
multinucleated myotubes differentiated from a manifesting carrier of DMD-hiPS
cells with XaXa pattern. AR transcripts were also equally transcribed from both
alleles in induced myotubes. Our results indicated that the inactivated X
chromosome in the patient's fibroblasts was activated during reprogramming, and
XCI occurred randomly during differentiation.
PMID- 28491100
TI - Increased Sensitization to Mold Allergens Measured by Intradermal Skin Testing
following Hurricanes.
AB - Objective. To report on changes in sensitivity to mold allergens determined by
changes in intradermal skin testing reactivity, after exposure to two severe
hurricanes. Methods. A random, retrospective allergy charts review divided into 2
groups of 100 patients each: Group A, patients tested between 2003 and 2010 prior
to hurricanes, and Group B, patients tested in 2014 and 2015 following
hurricanes. Reactivity to eighteen molds was determined by intradermal skin
testing. Test results, age, and respiratory symptoms were recorded. Chi-square
test determined reactivity/sensitivity differences between groups. Results.
Posthurricane patients had 34.6 times more positive results (p < 0.0001) at
weaker dilutions, all tested molds were found to be more reactive, and 95% had at
least one positive test versus only 62% before the hurricanes (p < 0.0001);
average mold reactivity was 55% versus 16% while 17% of patients reacted to the
entire panel versus none before the hurricanes (p < 0.0001). The posthurricane
population was younger (p < 0.001) and included more patients with asthma or
lower respiratory symptoms (p < 0.05). Conclusion. Reactivity and sensitization
to mold allergens increased compared to patients before the hurricanes. This
supports climatologists' hypothesis that environmental changes resulting from
hurricanes can be a health risk as reflected in increased allergic sensitivities
and symptoms and has significant implications for physicians treating patients
from affected areas.
PMID- 28491101
TI - Geospatial Assessment of Cholera in a Rapidly Urbanizing Environment.
AB - This study mapped out and investigated the spatial relationship between cholera
incidences and environmental risk factors in the study area. The study area was
stratified into eight zones. Water samples from each zone were collected and
analyzed to determine the colony forming units. GIS layers including housing
density, digitized roads, rivers, buildings, and cholera incidence data from
hospital archives were also collected and analyzed using ArcGIS 10.1. It was
observed that there was an association between the ERFs (p < 0.001). Similarly,
18 out of the 44 waste dump sites, seven out of 18 markets, and two out of 36
abattoirs were found near the historical cholera cases. Similarly, 4 (21.1%)
locations were traced to be predominantly close to rivers and waste dump site.
All the historical cholera cases were found adjoining to roads and buildings.
Highest CFU count was found in the wells and streams of areas with a cluster of
all the environmental risk factors and high housing density. This study revealed
that waste dump sites and market had the highest predisposing attribute while the
least was abattoir. The uniqueness of the study lies in the combination of
mapping and microbial analyses to identify and assess the pattern of cholera risk
and also to provide clear information for development of strategies for
environmental supervision.
PMID- 28491102
TI - The relationship between circulating concentrations of interleukin 17 and C
reactive protein in chronic spontaneous urticaria.
AB - BACKGROUND: Up-regulation of interleukin 17 (IL-17) family cytokines and acute
phase response have been observed in patients with chronic spontaneous urticaria
(CSU). It has been demonstrated that IL-17 stimulates C-reactive protein (CRP)
expression. AIM: To determine relationship between circulating concentrations of
IL-17 and CRP in CSU. METHODS: Concentrations of IL-17 in plasma and CRP in serum
were measured in patients with CSU of varying severity and in the healthy
subjects. RESULTS: IL-17 and CRP concentrations were significantly higher in CSU
patients as compared to the healthy subjects. In addition, there were significant
differences in IL-17 and CRP concentrations between CSU patients with mild,
moderate-severe symptoms and the healthy subjects. CRP did not correlate
significantly with IL-17. CONCLUSIONS: Increased circulating IL-17 concentration
may represent an independent index of systemic inflammatory response in CSU,
which is not related to increased CRP concentration.
PMID- 28491103
TI - Oleuropein Protects Cardiomyocyte against Apoptosis via Activating the
Reperfusion Injury Salvage Kinase Pathway In Vitro.
AB - Oleuropein, the main glycoside present in olives, has been reported to have
cardioprotective effect, but the exact mechanism has not been clearly elucidated.
This study attempted to clarify the cardioprotective effect of oleuropein against
simulated ischemia/reperfusion- (SI/R-) induced cardiomyocyte injury in vitro and
further explore the underlying mechanism. Here we confirmed that oleuropein
reduced the cell injury in neonatal rat cardiomyocyte induced by SI/R evidenced
by decreasing MTT dye reduction and LDH activity in the culture medium.
Meanwhile, the compound also inhibited reactive oxygen species excessive
generation and stabilized mitochondrial membrane potential after SI/R. The flow
cytometry assessment results indicated the inhibition of cellular apoptosis with
oleuropein treatment. Furthermore, western blot analysis showed that oleuropein
attenuated the expression of Cyt-C, c-caspase-3, and c-caspase-9, increased the
Bcl-2/Bax ratio, and enhanced the phosphorylation of ERK1/2 and Akt after SI/R.
However, the phosphorylation enhancement was partially abolished in the presence
of LY294002 (PI3K inhibitor) and U0126 (ERK inhibitor). All these findings
indicate that oleuropein has the protective potential against SI/R-induced injury
and its protective effect may be partly due to the attenuation of apoptosis via
the activation of the PI3K/Akt and ERK1/2 signaling pathways.
PMID- 28491104
TI - Effect of Tetramethylpyrazine on Atherosclerosis and SCAP/SREBP-1c Signaling
Pathway in ApoE-/- Mice Fed with a High-Fat Diet.
AB - Lipid metabolism dysregulation plays a crucial role in the occurrence of
atherosclerosis (As). SCAP/SREBP signaling is the main pathway for regulating
lipid metabolism. Tetramethylpyrazine (TMP), a Traditional Chinese Medicine (TCM)
for treating angina pectoris, has antiatherosclerotic effects and ameliorates
blood lipids disturbance. However, its precise mechanism remains unclear. This
study investigated the mechanism of TMP in ameliorating As in mice model. After
six weeks of high-fat diet, 30 ApoE-/- mice were randomized (n = 10) and treated
with Lipitor, TMP, or distilled water for six weeks. The serum blood lipids and
insulin levels were measured. The expressions of PAQR3, Insig-1, SCAP, SREBP-1c,
IRS-1, PI3K, Akt, and mTORC-1 in the adipose tissues were determined. The results
showed that TMP could significantly decrease blood lipids levels, insulin, and
corrected plaque area of the ApoE-/- mice as compared to the untreated mice (P <
0.05, P < 0.01). Moreover, TMP could significantly downregulate the expressions
of SCAP, SREBP-1c, PAQR3, IRS-1, PI3K, Akt, and mTORC1 (P < 0.01). Thus, TMP may
ameliorate lipid metabolism disorder and As by downregulating PAQR3 and
inhibiting SCAP/SREBP-1c signaling pathway. In addition, PI3K/Akt/mTORC1
signaling pathway may be involved in this process.
PMID- 28491105
TI - The Impacts of Chrysanthemum indicum Extract on Oxidative Stress and Inflammatory
Responses in Adjuvant-Induced Arthritic Rats.
AB - Chrysanthemum indicum has been used as a therapeutic agent against inflammation,
hypertension, and respiratory conditions for many years. This research's aim has
been to examine the antioxidant impacts that Chrysanthemum indicum extract (CIE)
has on the oxidative stress and inflammatory responses in adjuvant-induced
arthritic (AA) rats. 40 rats were categorised into 4 groups according to a
completely randomized approach: Group I involved normal control rats (CTRL) that
received a basal diet; Group II involved arthritic control rats (CTRL-AA) that
received the same diet; Group III involved rats that received a basal diet and 30
mg/kg CIE; and Group IV involved arthritic rats with the same diet as Group III
rats (CIE-AA). After injection with complete Freund's adjuvant, body weight,
arthritis score, and the serum levels of TNF-alpha, IL-1beta, IL-6,
myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), and
glutathione peroxidase (GSH-PX) were assessed. The results demonstrated that CIE
delayed the onset time of arthritis and decreased the clinical arthritis severity
score (P < 0.05). Observations of CIE-AA and CTRL-AA rats demonstrated that CIE
alleviates oxidative stress and inflammatory responses in CIE-AA group. In
conclusion, CIE alleviated oxidative stress and inflammatory responses, thereby
highlighting its potential use as a candidate for clinical treatments of
rheumatoid arthritis.
PMID- 28491106
TI - In Vitro Antioxidant and Antimicrobial Activities of Ephedra gerardiana (Root and
Stem) Crude Extract and Fractions.
AB - The utilization of medicinal plants to treat infectious disease is a common
practice in developing countries worldwide. The present study was aimed at
evaluating the crude extracts of Ephedra gerardiana (root and stem) with
different chemicals for antioxidant and antimicrobial (fungal and bacterial)
potential. The results revealed that the ethyl acetate fractions of E. gerardiana
(root and stem) have significant free radical scavenging potential with values
2.96 +/- 0.39 and 2.73 +/- 0.84 while n-butanol and aqueous fractions showed
IC502.69 +/- 0.26 and 3.44 +/- 0.69 ug/ml in stem. Furthermore, crude extract and
fractions also revealed promising antibacterial activities against all tested
microbial strains while aqueous fraction showed no activities against Bacillus
subtilis, Kleibsiella pneumoniae, and Pseudomonas aeruginosa. Interestingly, all
crude extracts and fractions were nonactive against fungal strain, Aspergillus
niger and Aspergillus flavus, as compare to control. In summary, the Ephedra
gerardiana (root and stem) extract and fraction possess antioxidant activities,
which might be helpful in preventing or slowing the progress of various oxidative
stresses, suggested to be a strong pharmaceutical agent.
PMID- 28491107
TI - Characteristics of Herbal Medicine Users and Adverse Events Experienced in South
Korea: A Survey Study.
AB - Background. This survey aimed to investigate the characteristics of users and
nonusers of herbal medicine and the adverse events experienced due to herbal
medicines in South Korea. Methods. The questionnaire consisted of safety, using
experience, using type, usage and nonusage reason, purchase location, and adverse
events of herbal medicine. The survey was administered by online. Results. Of the
total 1,134 respondents, 726 (64.0%) considered herbal medicine safe, and 693
(61.1%) answered that they have taken herbal medicines within the past year. Most
common place to purchase them was "TKM hospital or clinic" (63.6%), and most
participants (72.2%) took a decoction from a TKM institution. The biggest reason
for taking them was for "health improvement" (57.3%), and the reasons for not
using them was "medication not necessary" (63.7%). Among those who took herbal
medicines, 46 experienced adverse events, and the most frequently reported
symptoms were digestive disorders (52.2%). Of the 46 participants who experienced
adverse events, 20 (43.5%) were treated by TKM doctors. Conclusions. This study
suggests that regulation of herbal medicines is needed in order to resolve
problems related to the safety of herbal medicines.
PMID- 28491108
TI - Electroacupuncture Improves Cognitive Deficits through Increasing Regional
Cerebral Blood Flow and Alleviating Inflammation in CCI Rats.
AB - Objective. To investigate the effect of EA on regional cerebral blood flow,
cognitive deficits, inflammation, and its probable mechanisms in chronic cerebral
ischemia (CCI) rats. Methods. Rats were assigned randomly into sham operation
group (sham group) and operation group. For operation group, CCI model was
performed using the permanent bilateral common carotid artery occlusion (BCCAO)
method, and then rats were further randomly divided into model group and
electroacupuncture (EA) group. 2/15 Hz low-frequency pulse electric intervention
was applied at "Baihui" and "Dazhui" acupoints in EA group. Four weeks later,
Morris water maze test was adopted to assess the cognitive function, using laser
Doppler flowmetry to test changes of regional cerebral blood flow (rCBF); double
antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) to measure
proinflammatory cytokines (IL-6, TNF-alpha, and IL-1beta); western blot to test
the protein expression quantities of proinflammatory cytokines, JAK2, and STAT3;
and RT-PCR to test JAK2 mRNA and STAT3 mRNA in the hippocampus in each group.
Results. Compared with the model group, learning and memory abilities and rCBF
and IL-6 expression of the EA group enhanced markedly; IL-1beta and JAK2
significantly decreased; TNF-alpha and STAT3 also declined, but the difference
was not apparent. Conclusion. Our research suggests that EA can improve cognitive
deficits which may be induced by increasing rCBF and anti-inflammatory effect.
PMID- 28491109
TI - Retracted: Expression Profiling of Transcriptome and Its Associated Disease Risk
in Yang Deficiency Constitution of Healthy Subjects.
AB - [This retracts the article DOI: 10.1155/2016/1493098.].
PMID- 28491110
TI - Tai-Chi-Chuan Exercise Improves Pulmonary Function and Decreases Exhaled Nitric
Oxide Level in Both Asthmatic and Nonasthmatic Children and Improves Quality of
Life in Children with Asthma.
AB - Tai-Chi-Chuan (TCC) is an exercise of low-to-moderate intensity which is suitable
for asthmatic patients. The aim of our study is to investigate improvements of
the lung function, airway inflammation, and quality of life of asthmatic children
after TCC. Participants included sixty-one elementary school students and they
were divided into asthmatic (n = 29) and nonasthmatic (n = 32) groups by the
International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire.
Among them, 20 asthmatic and 18 nonasthmatic children volunteered to participate
in a 60-minute TCC exercise weekly for 12 weeks. Baseline and postintervention
assessments included forced expiratory volume in one second (FEV1), forced vital
capacity (FVC), peak expiratory flow rate (PEFR), fractional exhaled nitric oxide
(FeNO) level, and Standardised Pediatric Asthma Quality of Life Questionnaire
(PAQLQ(S)). After intervention, the level of FeNO decreased significantly; PEFR
and the FEV1/FVC also improved significantly in both asthmatic group and
nonasthmatic group after TCC. The asthmatic children also had improved quality of
life after TCC. The results indicated that TCC could improve the pulmonary
function and decrease airway inflammation in both children with mild asthma and
those without asthma. It also improves quality of life in mild asthmatic
children. Nevertheless, further studies are required to determine the effect of
TCC on children with moderate-to-severe asthma.
PMID- 28491111
TI - Ficus hispida Bark Extract Prevents Nociception, Inflammation, and CNS
Stimulation in Experimental Animal Model.
AB - Background. Ficus hispida is traditionally used in the ailment of pain,
inflammation, and neurological disorders. The present study set out to evaluate
the in vivo antinociceptive, anti-inflammatory, and sedative activity of the
ethanol extract of Ficus hispida bark (EFHB). Methods. The antinociceptive
activity of EFHB was evaluated by using acetic acid induced writhing, formalin,
hot plate, and tail immersion methods in Swiss albino mice. Its anti-inflammatory
activity was assessed by using carrageenan and histamine induced rat paw oedema
test in Wister rats. The central stimulating activity was studied by using
pentobarbital induced hypnosis, hole cross, and open field tests in Swiss albino
mice. Results. EFHB demonstrated antinociceptive activity both centrally and
peripherally. It showed 62.24% of writhing inhibition. It significantly inhibited
licking responses in early (59.29%) and late phase (71.61%). It increased the
reaction time to the thermal stimulus in both hot plate and tail immersion. It
inhibited the inflammation to the extent of 59.49%. A substantial increase in
duration of sleep up to 60.80 min and decrease of locomotion up to 21.70 at 400
mg/kg were also observed. Conclusion. We found significant dose dependent
antinociceptive, anti-inflammatory, and sedative properties of EFHB in
experimental animal models.
PMID- 28491112
TI - Medicinal Plants and Natural Active Compounds for Cancer
Chemoprevention/Chemotherapy.
PMID- 28491113
TI - Antioxidant, Anti-Inflammatory, and Analgesic Activities of Agrimonia eupatoria
L. Infusion.
AB - Agrimony (Agrimonia eupatoria L.) (Ae) is used in traditional medicine to treat
inflammatory and oxidative related diseases. Therefore, this study focuses on the
anti-inflammatory and analgesic potential of Ae infusion (AeI). Phenolic
compounds characterization was achieved by HPLC-PDA-ESI/MS n . To evaluate
antioxidant potential, 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion,
hydroxyl radical, and SNAP assays were used. In vitro anti-inflammatory activity
of AeI was investigated in LPS-stimulated macrophages by measuring the NO
production. In vivo anti-inflammatory activity was validated using the mouse
carrageenan-induced paw edema model. Peripheral and central analgesic potential
was evaluated using the acetic acid-induced writhing and hot-plate tests,
respectively, as well as the formalin assay to assess both activities. The safety
profile was disclosed in vitro and in vivo, using MTT and hematoxylin assays,
respectively. Vitexin, quercetin O-galloyl-hexoside, and kaempferol O-acetyl
hexosyl-rhamnoside were referred to in this species for the first time. AeI and
mainly AePF (Ae polyphenolic fraction) showed a significant antiradical activity
against all tested radicals. Both AeI and AePF decreased NO levels in vitro, AePF
being more active than AeI. In vivo anti-inflammatory and analgesic activities
were verified for both samples at concentrations devoid of toxicity. Agrimony
infusion and, mainly, AePF are potential sources of antiradical and anti
inflammatory polyphenols.
PMID- 28491114
TI - Optimal Solubility of Diclofenac beta-Cyclodextrin in Combination with Local
Anaesthetics for Mesotherapy Applications.
AB - Because of low injection volume, the recently marketed injectable solution of
diclofenac in complex with beta-cyclodextrin (Akis(r), IBSA Farmaceutici Italia)
is an ideal candidate for mesotherapy applications. In this study, we
investigated the solubility of Akis, 25 and 50 mg/kg, in combination with various
local anaesthetics (lidocaine, mepivacaine, bupivacaine, levobupivacaine, and
ropivacaine) at different concentrations in aqueous vehicles (normal saline,
sterile water, or bicarbonate). Final injection mixtures were classified as
limpid, turbid, or milky at visual analysis under standardized conditions. We
found that (i) the use of sterile water for injections or normal saline as
vehicles to dilute Akis in combination with whatever local anaesthetic normally
results in milky solutions and therefore is not recommended; (ii) using
bicarbonate, optimal solubility was obtained combining Akis with lidocaine, both
1 and 2%, or mepivacaine, both 1 and 2%, whereas solutions were turbid in
combination with bupivacaine, levobupivacaine, or ropivacaine. Thus, we recommend
that Akis is used in combination with lidocaine or mepivacaine in a bicarbonate
vehicle.
PMID- 28491115
TI - Therapeutic Risk and Benefits of Concomitantly Using Herbal Medicines and
Conventional Medicines: From the Perspectives of Evidence Based on Randomized
Controlled Trials and Clinical Risk Management.
AB - Despite increased awareness of the potential of herb-drug interactions (HDIs),
the lack of rigorous clinical evidence regarding the significance provides a
challenge for clinicians and consumers to make rational decisions about the safe
combination of herbal and conventional medicines. This review addressed HDIs
based on evidence from randomized controlled trials (RCTs). Literature was
identified by performing a PubMed search till January 2017. Risk description and
clinical risk management were described. Among 74 finally included RCTs, 17 RCTs
(22.97%) simply addressed pharmacodynamic HDIs. Fifty-seven RCTs (77.03%)
investigated pharmacokinetic HDIs and twenty-eight of them showed potential or
actual clinical relevance. The extent of an HDI may be associated with the
factors such as pharmacogenomics, dose of active ingredients in herbs, time
course of interaction, characteristics of the object drugs (e.g., administration
routes and pharmacokinetic profiles), modification of herbal prescription
compositions, and coexistence of inducers and inhibitors. Clinical professionals
should enhance risk management on HDIs such as increasing awareness of potential
changes in therapeutic risk and benefits, inquiring patients about all currently
used conventional medicines and herbal medicines and supplements, automatically
detecting highly substantial significant HDI by computerized reminder system,
selecting the alternatives, adjusting dose, reviewing the appropriateness of
physician orders, educating patients to monitor for drug-interaction symptoms,
and paying attention to follow-up visit and consultation.
PMID- 28491116
TI - A Randomized Clinical Trial Comparing the Effectiveness of Electroacupuncture
versus Medium-Frequency Electrotherapy for Discogenic Sciatica.
AB - Objective. To investigate the short- and long-term effects of electroacupuncture
(EA) compared with medium-frequency electrotherapy (MFE) on chronic discogenic
sciatica. Methods. One hundred participants were randomized into two groups to
receive EA (n = 50) or MFE (n = 50) for 4 weeks. A 28-week follow-up of the two
groups was performed. The primary outcome measure was the average leg pain
intensity. The secondary outcome measures were the low back pain intensity,
Oswestry Disability Index (ODI), patient global impression (PGI), drug use
frequency, and EA acceptance. Results. The mean changes in the average leg pain
numerical rating scale (NRS) scores were 2.30 (1.86-2.57) and 1.06 (0.62-1.51) in
the EA and MFE groups at week 4, respectively. The difference was significant (P
< 0.001). The long-term follow-up resulted in significant differences. The
average leg pain NRS scores decreased by 2.12 (1.70-2.53) and 0.36 (-0.05-0.78)
from baseline in the EA and MFE groups, respectively, at week 28. However, low
back pain intensity and PGI did not differ significantly at week 4. No serious
adverse events occurred. Conclusions. EA showed greater short-term and long-term
benefits for chronic discogenic sciatica than MFE, and the effect of EA was
superior to that of MFE. The study findings warrant verification. This trial was
registered under identifier ChiCTR-IPR-15006370.
PMID- 28491117
TI - Herpes virus seroepidemiology in the adult Swedish population.
AB - BACKGROUND: Herpes viruses establish a life-long latency and can cause symptoms
during both first-time infection and later reactivation. The aim of the present
study was to describe the seroepidemiology of Herpes simplex type 1 (HSV1),
Herpes simplex type 2 (HSV2), Cytomegalovirus (CMV), Varicella Zoster virus (VZV)
and Human herpes virus type 6 (HHV6) in an adult Swedish population (35-95 years
of age). METHODS: Presence of antibodies against the respective viruses in serum
from individuals in the Betula study was determined with an enzyme-linked
immunosorbent assay (ELISA). Singular samples from 535 persons (53.9% women, mean
age at inclusion 62.7 +/- 14.4 years) collected 2003-2005 were analyzed for the
five HHVs mentioned above. In addition, samples including follow-up samples
collected 1988-2010 from 3,444 persons were analyzed for HSV. RESULTS: Prevalence
of HSV1 was 79.4%, HSV2 12.9%, CMV 83.2%, VZV 97.9%, and HHV6 97.5%. Herpes virus
infections were more common among women (p = 0.010) and a lower age-adjusted HSV
seroprevalence was found in later birth cohorts (p < 0.001). The yearly incidence
of HSV infection was estimated at 14.0/1000. CONCLUSION: Women are more often
seropositive for HHV, especially HSV2. Age-adjusted seroprevalence for HSV was
lower in later birth cohorts indicating a decreasing childhood and adolescent
risk of infection.
PMID- 28491118
TI - The head morphology of Pyrrhosoma nymphula larvae (Odonata: Zygoptera) focusing
on functional aspects of the mouthparts.
AB - BACKGROUND: The understanding of concerted movements and its underlying
biomechanics is often complex and elusive. Functional principles and hypothetical
functions of these complex movements can provide a solid basis for biomechanical
experiments and modelling. Here a description of the cephalic anatomy of
Pyrrhosoma nymphula (Zygoptera, Coenagrionidae) focusing on functional aspects of
the mouthparts using micro computed tomography (MUCT) is presented. RESULTS: We
compared six different instars of the damselfly P. nymphula as well as one instar
of the dragonfly Aeshna cyanea and Epiophlebia superstes each. In total 42 head
muscles were described with only minor differences of the attachment points
between the examined species and the absence of antennal muscle M.
scapopedicellaris medialis (0an7) in Epiophlebia as a probable apomorphy of this
group. Furthermore, the ontogenetic differences between the six larval instars
are minor; the only considerable finding is the change of M. submentopraementalis
(0la8), which is dichotomous in the early instars (I1,I2 and I3) with a second
point of origin at the postero-lateral base of the submentum. This dichotomy is
not present in any of the older instars studied (I6, middle-late and pen
ultimate). CONCLUSION: However, the main focus of the study herein, is to use
these detailed morphological descriptions as basis for hypothetic functional
models of the odonatan mouthparts. We present blueprint like description of the
mouthparts and their musculature, highlighting the caused direction of motion for
every single muscle. This data will help to elucidate the complex concerted
movements of the mouthparts and will contribute to the understanding of its
biomechanics not in Odonata only.
PMID- 28491119
TI - Association of adipokines with blood pressure, arterial elasticity and cardiac
markers in dialysis patients: cross-sectional analysis of baseline data from a
cohort study.
AB - BACKGROUND: Adipokines are a set of cytokines secreted by white adipose tissue
that have been suggested to be involved in the development of cardiovascular
diseases. We aimed to evaluate the cross-sectional associations of a panel of
representative adipokines with cardiovascular measures in a cohort of
hemodialysis patients. METHODS: We measured plasma adiponectin, resistin,
plasminogen activator inhibitor-1 (PAI-1), leptin, monocyte chemotactic protein 1
(MCP-1) and adipsin levels in 366 dialysis patients and 60 healthy controls. The
associations of these adipokines with systolic blood pressure (assessed by
ambulatory blood pressure monitoring), pulse wave velocity (PWV) and cardiac
markers (BNP, NT-proBNP, Troponin I, Troponin T) in these patients were
determined by general linear models with stepwise adjustment for covariates.
RESULTS: In unadjusted comparison with controls, dialysis patients showed
increased adiponectin, resistin, MCP-1 and adipsin levels, decreased PAI-1
concentrations (all p <0.001) and similar leptin levels (p = 0.82). On adjustment
for body mass index and diabetes, however, the PAI-1 level was comparable between
group (p = 0.06), whereas leptin levels became significantly higher in the
patients(p <0.001). Higher adiponectin, lower PAI-1 and leptin levels were
associated with higher systolic blood pressure, even after extensive adjustment
(all p <= 0.01). Adiponectin was also consistently and inversely associated with
PWV in fully adjusted models (p = 0.003). Resistin, PAI-1, leptin and adipsin
showed negative associations with one or more circulating cardiac markers (all p
<= 0.02). CONCLUSIONS: We found significant associations between adipokines and
cardiovascular measures. Our data suggest the possible involvement of adipokines
in cardiovascular modulation in dialysis patients.
PMID- 28491120
TI - Microscopy of Physcomitrella patens sperm cells.
AB - BACKGROUND: Archegoniates (bryophytes, ferns and gymnosperms), such as the moss
Physcomitrella patens, possess freely motile sperm cells (spermatozoids) which
reach the egg cell via surface water. Although these motile flagellated sperm
cells are a traditional botanical subject, they have not been thoroughly analysed
in the flagship non-seed plant model species P. patens. Protocols are required to
determine the behaviour of wild type sperms as a prerequisite for future research
such as the characterization of mutants or factors that influence sperm number,
morphology, viability and motility. RESULTS: Here, we present protocols for the
observation of fixed, as well as live sperms utilizing a standard microscope at
intermediate magnifications. Fixed samples can be used for the fast assessment of
sperm number and morphology. To determine functionality, the observation of live
sperms is required. Protocols for determining both sperm motility and viability
are provided, allowing both parameters to be distinguished. CONCLUSIONS: These
step-by-step protocols are particularly useful for researchers so far not
familiar with the analysis of motile gametes and are meant to aid the
establishment and improvement of these analyses in order to stimulate research on
spermatogenesis in the moss model species P. patens.
PMID- 28491121
TI - Development of a new heat tolerance assay system for rice spikelet sterility.
AB - BACKGROUND: Reduction in rice yield caused by high temperature-induced spikelet
sterility has been a serious concern in rice production. To date, several
screening methods have been used, although their reproducibility is sometimes
poor due to artifacts mainly caused by varietal differences in heading dates and
panicle heights (i.e., the distance from the lamps). METHODS: We have developed a
novel assay system for heat-induced spikelet sterility by using artificial rice
paddies in phytotrons to conduct a highly reproducible assay throughout a year.
Plants restricted to the main culm were treated under a series of heat
conditions, and height uniformity of each plant was ensured by using height
adjustable pots. RESULTS: Results suggested that a 3-day heat treatment of 35
degrees C-day/29 degrees C-night cycles was the most suitable condition. Under
the treatment, two distinct groups were identified among nine heat tolerant
cultivars, with no varietal difference in panicle temperature, indicating that
the system is capable of eliminating the varietal difference in panicle
temperature. CONCLUSIONS: It is concluded that the assay system would be a
powerful tool for selecting heat tolerant varieties, as well as the analysis of
genetic factors from various cultivars, eliminating potential artifacts.
PMID- 28491123
TI - Editorial.
PMID- 28491122
TI - In situ measurement of Scots pine needle PRI.
AB - BACKGROUND: The Photochemical Reflectance Index (PRI) calculated from narrow-band
spectral reflectance data is a vegetation index which is increasingly used as an
indicator of photosynthetic activity. The leaf-level link between the status of
photosynthetic apparatus and PRI has been robustly established under controlled
light conditions. However, when a whole canopy is measured instantaneously, the
PRI signal is heavily modified by vegetation structure and local variations in
incident light conditions. To apply PRI for monitoring the photosynthesis of
whole canopies under natural conditions, these large-scale measurements need to
be validated against simultaneous leaf PRI. Unfortunately, PRI changes
dynamically with incident light and has a large natural variation. No generally
accepted procedure exists today for determining the PRI of canopy elements in
situ. RESULTS: We present a successful procedure for in situ measurements of
needle PRI. We describe, characterize and test an optical measurement protocol
and demonstrate its applicability in field conditions. The measurement apparatus
consisted of a light source, needle clip, spectroradiometer and a controlling
computer. The light level inside the clip was approximately two-thirds of that on
sunlit needle surfaces at midday. During each measurement the needle was inserted
into the clip for approximately 5 s. We found no near-instantaneous changes (sub
second scale jumps) in PRI during the measurements. The time constants for PRI
variation in light to full shade acclimations were approximately 10 s. The
procedure was successfully applied to monitor the greening-up of Scots pine
trees. We detected both facultative (diurnal) PRI changes of 0.02 (unitless) and
constitutive (seasonal) variations of 0.1. In order to reliably detect the
facultative PRI change of 0.02, 20 needles need to be sampled from both sunlit
and shaded locations. CONCLUSIONS: We established a robust procedure for
irradiance-dependent leaf (needle) PRI measurements, facilitating empirical
scaling of PRI from leaf (needle) to full canopy level and the application of PRI
to monitoring the changes in highly structured vegetation. The measured time
constants, and facultative and constitutive PRI variations support the use of an
artificial light for in situ PRI measurements at leaf (needle) level.
PMID- 28491124
TI - Strategies to reduce the global burden of direct maternal deaths.
AB - The leading direct causes of the estimated 196 maternal deaths per 100,000 live
births globally are postpartum haemorrhage, the hypertensive disorders of
pregnancy, obstructed labour, unsafe abortion and obstetric sepsis. Of the
Sustainable Development Goals, one (Sustainable Development Goal 3.1)
specifically addresses maternal mortality; by 2030, the goal is to reduce the
global maternal mortality ratio to less than 70 per 100,000 live births. Eleven
other Sustainable Development Goals provide opportunities to intervene.
Unapologetically, this review focusses the reader's attention on health advocacy
and its central role in altering the risks that many of the world's women face
from direct obstetric causes of mortality. Hard work to alter social determinants
of health and health outcomes remains. That work needs to start today to improve
the health and social equality of today's girls who will be the women delivering
their babies in 2030.
PMID- 28491126
TI - Developing obstetric medicine training in Latin America.
AB - Maternal mortality is an important indicator of health in populations around the
world. The distribution of maternal mortality ratio globally shows that middle-
and low-income countries have ~99% of the mortality burden. Most countries of
Latin America are considered to be middle- or low-income countries, as well as
areas of major inequities among the different social classes. Medical problems in
pregnancy remain an important cause of morbidity and mortality in this region.
Previous data indicate the need for a call to action for adequate diagnosis and
care of medical diseases in obstetric care. The impact of nonobstetric and
medical pathologies on maternal mortality in Latin America is largely unknown. In
Latin America, two educational initiatives have been proposed to improve skills
in maternity care. The Advanced Life Support in Obstetrics (ALSO(r)) was first
started to address obstetric emergencies, and subsequently adapted for low-middle
income country settings as the Global ALSO(r). In parallel, the Latin American
obstetric anesthesia community has progressively focused on improvement of
several intrapartum/intraoperative issues, which has secondarily taken them to
embrace the obstetric medicine area on interest and join the former initiatives.
In the present review, we summarize the available data regarding medical
morbidity and mortality in pregnancy in Latin America, as well as the challenges,
achievements, issues, initiatives, and future directions encouraging maternal
health educators, health care trainers, and physicians in middle- and low-income
countries, such as many Latin American ones, to improve and/or change attitudes,
if needed, on current clinical practice.
PMID- 28491125
TI - Indirect maternal deaths: UK and global perspectives.
AB - Indirect maternal deaths outnumber direct deaths due to obstetric causes in many
high-income countries, and there has been a significant increase in the
proportion of maternal deaths due to indirect medical causes in low- to middle
income countries. This review presents a detailed analysis of indirect maternal
deaths in the UK and a perspective on the causes and trends in indirect maternal
deaths and issues related to care in low- to middle-income countries. There has
been no significant decrease in the rate of indirect maternal deaths in the UK
since 2003. In 2011-2013, 68% of all maternal deaths were due to indirect causes,
and cardiac disease was the single largest cause. The major issues identified in
care of women who died from an indirect cause was a lack of clarity about which
medical professional should take responsibility for care and overall management.
Under-reporting and misclassification result in underestimation of the rate of
indirect maternal deaths in low- to middle-income countries. Causes of indirect
death include a range of communicable diseases, non-communicable diseases and
nutritional disorders. There has been evidence of a shift in incidence from
direct to indirect maternal deaths in many low- to middle-income countries due to
an increase in non-communicable diseases among women in the reproductive age. The
gaps in care identified include poor access to health services, lack of
healthcare providers, delay in diagnosis or misdiagnosis and inadequate follow-up
during the postnatal period. Irrespective of the significant gains made in
reducing maternal mortality in many countries worldwide, there is evidence of a
steady increase in the rate of indirect deaths due to pre-existing medical
conditions. This heightens the need for research to generate evidence about the
risk factors, management and outcomes of specific medical comorbidities during
pregnancy in order to provide appropriate evidence-based multidisciplinary care
across the entire pathway: pre-pregnancy, during pregnancy and delivery, and
postpartum.
PMID- 28491127
TI - Global initiatives in maternal and newborn health.
AB - In 2015, 17 sustainable development goals were established for 2030. These global
goals aim to ensure healthy lives and promote wellbeing for all. In support of
the sustainable development goals, the World Health Organization proposed a new
global strategy for women's, children's, and adolescents' health in 2016 with
three overarching objectives: to survive, to thrive, and to transform. We are now
globally seeking not only to end preventable deaths but also to ensure health and
wellbeing, and expand enabling environments. This strategy builds on several
prior initiatives in maternal and newborn health, such as the Every Woman, Every
Child initiative, and the strategy to end preventable maternal mortality and
implementation of an action plan to end preventable newborn death. This
confluence of initiatives, strategies, and novel financing mechanisms under the
umbrella of the sustainable development goals and the global strategy pave the
way for a global agenda in which securing women's health is critical.
PMID- 28491128
TI - Non-communicable diseases during pregnancy in low and middle income countries.
AB - Apart from the risks of obstetric complications like haemorrhage and eclampsia, a
large number of medical conditions affect pregnancy and result in adverse
outcomes for both the mother and offspring. Non-communicable diseases in
pregnancy are becoming increasingly important in contributing to death and poor
health. Changes in the patterns and distribution of these conditions mean that we
need new perspectives and ways of dealing with these challenges for the future.
This article reviews the burden of ill-health due to non-communicable diseases
during pregnancy in low and middle income countries and presents some paradigms
relevant to public health and health system needs of the future.
PMID- 28491129
TI - The XXI International Society of Hypertension in Pregnancy meeting, Sao Paulo,
Brazil - A global health perspective.
AB - The 21st International Society of Hypertension in Pregnancy (ISSHP) meeting was
held in Sao Paulo, Brazil from 23 to 26 October 2016. The discourse at this
Congress brought global maternal health into the foray among basic science and
clinical research. In concordance with the United Nations sustainable development
goals which warrant an integrated view to health with investments in adolescence
and childhood, the research at Congress focussed on a 'life course' approach to
maternal health - examining intergenerational effects of maternal obesity and
hypertension on the behavioral and physical developments of infants. Bringing in
research from the Global South highlighted inequities in treatment and management
of women with hypertensive disorders of pregnancy, in addition to the challenges
in adoption of recommendations generated in Global North. The evidence shared can
serve as platform for further discourse on global maternal health and in
generating accountability to close the 'evidence to policy' gap.
PMID- 28491130
TI - Advocacy is essential to supporting women with pre-eclampsia.
AB - Advocacy has a critical role in advancing the maternal health agenda. Patient
advocacy groups can hold governments and other stakeholders accountable and
ensure that commitments are translated into concrete action. This article
highlights the advocacy efforts of the Preeclampsia Foundation, a patient
advocacy organisation that aims to improve the diagnosis, management, and
prevention of pre-eclampsia through research and improved healthcare practices. A
number of challenges continue to face maternal health advocacy especially in low-
and middle-income countries. Future directions include developing a strategic
focus for advocacy, effectively engaging citizens to build a culture of
accountability, and monitoring and evaluation of advocacy efforts.
PMID- 28491131
TI - Obstetric medical care in the United States of America.
AB - The current models of obstetric medical care utilized in the United States, how
those models fit in with the overall care system, and ways to increase the role
of obstetric internists will be reviewed.
PMID- 28491132
TI - Obstetric medical care and training in the United Kingdom.
AB - The UK confidential enquiry into maternal deaths identified poor management of
medical problems in pregnancy to be a contributory factor to a large proportion
of indirect maternal deaths. Maternal (obstetric) medicine is an exciting
subspecialty that encompasses caring for both women with pre-existing medical
conditions who become pregnant, as well as those who develop medical conditions
in pregnancy. Obstetrics and gynaecology trainees have some exposure to maternal
medicine through their core curriculum and can then complete an advanced training
skills module, subspecialise in maternal-fetal medicine or take time out to
complete the Royal College of Physicians membership examination. Physician
training has limited exposure to medical problems in pregnancy and has therefore
prompted expansion of the obstetric physician role to ensure physicians with
adequate expertise attend joint physician-obstetrician clinics. This article
describes the role of an obstetric physician in the UK and the different career
pathways available to physicians and obstetricians interested in maternal
medicine.
PMID- 28491133
TI - The way forward.
AB - Improving maternal health and reducing maternal morbidity and mortality into the
future will require a range of health-related and non-health-related strategies.
The latter include education for women, better communication, access to transport
and technology and cultural change. The role of obstetric medicine practice,
research and education in achieving these objectives is discussed in this
article. We need to recognise that it will require improvements in health
provision and access to achieve our goal of safer childbirth for women and babies
throughout the world.
PMID- 28491134
TI - Traditional practices and adverse pregnancy outcomes in migrant women.
AB - Traditional practices during pregnancy may lead to adverse outcomes in migrant
women. Very little is known regarding the efficacy or safety of many cultural
practices during pregnancy, and research is required to address this deficiency
in knowledge. Greater awareness of traditional practices by health professionals
may result in improved pregnancy outcomes in migrant women.
PMID- 28491135
TI - Highlights from the 15th St Gallen International Breast Cancer Conference 15-18
March, 2017, Vienna: tailored treatments for patients with early breast cancer.
AB - The 15th St Gallen International Breast Cancer Conference was held in Vienna for
the second time, from 15th-18th March 2017. 4000 people from 105 countries all
over the world were invited to take part in the event. The real highlight of the
conference was the last day with the International Consensus Session which was
chaired by around 50 experts on breast cancer worldwide. With reference to data
from scientific research, the consensus panel tried to offer guidelines for the
management of breast cancer with the aim of providing patients with optimal
treatment. The topics covered focused on the treatment of breast cancer,
consideration of surgery, radiotherapy, neo-adjuvant, and adjuvant systemic
therapy for breast cancer, as well as genetics and prevention of breast cancer.
In particular, in terms of precision medicine, an important topic of the
conference was 'is it possible to think that it could become routine in clinical
practice to use immunotherapy and targeted therapy based on genetic signatures?'
In view of personalised therapy, it is important to take into consideration
women's treatment preferences. It is also important not only to offer guidelines
which help breast cancer experts all over the world to choose the proper
treatment for women with breast cancer but also to discuss the pros and cons of
the therapy with the patient. This allows for a better understanding of the
disease. 'From the maximum tolerable to the minimum effective treatment: it is
essential to escalate treatment when necessary and to de-escalate when
unnecessary'. These few words could summarise the meaning of the 15th St Gallen
International Breast Cancer Conference. Prof Martine Piccart-Gebhart was awarded
with the St Gallen International Breast Cancer Award 2017 for her fundamental
clinical research contribution and Prof Giuseppe Curigliano with the Umberto
Veronesi Memorial Award which aims to recognise a physician's leading role in
advancing the science and care of breast cancer patients. Curigliano, in his
lecture, spoke about the revolutionary immunotherapy in the clinical management
of breast cancer (BC). For the development of these therapies, it is necessary to
identify the genetic determinants of BC immune phenotypes in which The Cancer
Genome Atlas (TCGA) has contributed towards this. For example, the T helper (Th
1) phenotype (ICR4), which also exhibits upregulation of immune-regulatory
transcripts (eg. PDL1, PD1, FOXP3, IDO1, and CTLA4), was associated with
prolonged patients' survival. Chromosome segment 4q21, which includes genes
encoding the Th-1 chemokines CXCL9-11, was significantly amplified only in the
immune favourable phenotype (ICR4). The mutation and neo-antigen load
progressively decreased from ICR4 to ICR1 but could not explain immune phenotypic
differences. Mutations of TP53 were enriched in the immune favourable phenotype
(ICR4). Instead, the presence of MAP3K1 and MAP2K4 mutations were closely
associated with an immune unfavourable phenotype (ICR1). Using both the TCGA and
the validation dataset, the degree of MAPK deregulation segregates BC according
to their immune disposition. These findings suggest that mutational-driven
deregulation of MAPK pathways is linked to the negative regulation of
intratumoural immune response in BC. The main themes of this congress were: 1)
Surgery of the primary tumour and margins; 2) Surgery of the axilla; 3)
Radiotherapy: hypofractionated, 'boost' to tumour bed, partial breast, regional
node, after mastectomy, advanced technology; 4) Pathology: subtypes, TILs; 5)
Multi-gene signatures and therapy; 6) Endocrine therapy: pre- and post-menopausal
and duration; 7) Chemotherapy: subtypes, stages; 8) Anti-HER-2 therapy; 9) Neo
adjuvant therapy; 10) Adjuvant bisphosponates; 11) Adjuvant diet and exercise.
PMID- 28491136
TI - Applications of microalgal biofilms for wastewater treatment and bioenergy
production.
AB - BACKGROUND: Microalgae have shown clear advantages for the production of biofuels
compared with energy crops. Apart from their high growth rates and substantial
lipid/triacylglycerol yields, microalgae can grow in wastewaters (animal,
municipal and mining wastewaters) efficiently removing their primary nutrients
(C, N, and P), heavy metals and micropollutants, and they do not compete with
crops for arable lands. However, fundamental barriers to the industrial
application of microalgae for biofuel production still include high costs of
removing the algae from the water and the water from the algae which can account
for up to 30-40% of the total cost of biodiesel production. Algal biofilms are
becoming increasingly popular as a strategy for the concentration of microalgae,
making harvesting/dewatering easier and cheaper. RESULTS: We have isolated and
characterized a number of natural microalgal biofilms from freshwater, saline
lakes and marine habitats. Structurally, these biofilms represent complex
consortia of unicellular and multicellular, photosynthetic and heterotrophic
inhabitants, such as cyanobacteria, microalgae, diatoms, bacteria, and fungi.
Biofilm #52 was used as feedstock for bioenergy production. Dark fermentation of
its biomass by Enterobacter cloacae DT-1 led to the production of 2.4 mol of
H2/mol of reduced sugar. The levels and compositions of saturated, monosaturated
and polyunsaturated fatty acids in Biofilm #52 were target-wise modified through
the promotion of the growth of selected individual photosynthetic inhabitants.
Photosynthetic components isolated from different biofilms were used for
tailoring of novel biofilms designed for (i) treatment of specific types of
wastewaters, such as reverse osmosis concentrate, (ii) compositions of total
fatty acids with a new degree of unsaturation and (iii) bio-flocculation and
concentration of commercial microalgal cells. Treatment of different types of
wastewaters with biofilms showed a reduction in the concentrations of key
nutrients, such as phosphates, ammonia, nitrates, selenium and heavy metals.
CONCLUSIONS: This multidisciplinary study showed the new potential of natural
biofilms, their individual photosynthetic inhabitants and assembled new
algal/cyanobacterial biofilms as the next generation of bioenergy feedstocks
which can grow using wastewaters as a cheap source of key nutrients.
PMID- 28491137
TI - Boosting LPMO-driven lignocellulose degradation by polyphenol oxidase-activated
lignin building blocks.
AB - BACKGROUND: Many fungi boost the deconstruction of lignocellulosic plant biomass
via oxidation using lytic polysaccharide monooxygenases (LPMOs). The application
of LPMOs is expected to contribute to ecologically friendly conversion of biomass
into fuels and chemicals. Moreover, applications of LPMO-modified cellulose-based
products may be envisaged within the food or material industry. RESULTS: Here, we
show an up to 75-fold improvement in LPMO-driven cellulose degradation using
polyphenol oxidase-activated lignin building blocks. This concerted enzymatic
process involves the initial conversion of monophenols into diphenols by the
polyphenol oxidase MtPPO7 from Myceliophthora thermophila C1 and the subsequent
oxidation of cellulose by MtLPMO9B. Interestingly, MtPPO7 shows preference
towards lignin-derived methoxylated monophenols. Sequence analysis of genomes of
336 Ascomycota and 208 Basidiomycota reveals a high correlation between MtPPO7
and AA9 LPMO genes. CONCLUSIONS: The activity towards methoxylated phenolic
compounds distinguishes MtPPO7 from well-known PPOs, such as tyrosinases, and
ensures that MtPPO7 is an excellent redox partner of LPMOs. The correlation
between MtPPO7 and AA9 LPMO genes is indicative for the importance of the coupled
action of different monooxygenases in the concerted degradation of
lignocellulosic biomass. These results will contribute to a better understanding
in both lignin deconstruction and enzymatic lignocellulose oxidation and
potentially improve the exploration of eco-friendly routes for biomass
utilization in a circular economy.
PMID- 28491138
TI - Clinicohematological and cytogenetic profile of myelodysplastic syndromes in
Pakistan-compare and contrast.
AB - BACKGROUND: Myelodysplastic syndromes (MDS) are clonal stem cell disorders
exhibiting cytopenias, ineffective hematopoiesis and morphological dysplasia.
Bone marrow cytogenetics, inspite of being incorporated as mandatory tool in
diagnosis are done less frequently due to limited availability of this technique
in Pakistan. The aim of the study was to study baseline clinicohematological and
cytogenetic characteristics of patients presenting with de novo MDS. RESULTS: A
retrospective cross sectional study was done at National Institute of Blood
Diseases and Bone Marrow Transplantation, Karachi, Pakistan from 2010 to 2016.
Total of 177 patients were included in the study having median age 51 years and
male to female ratio of 3:1. Pancytopenia was observed in 80 (45%) patients and
bicytopenia in 74 (42%). Mean Hb% was 7.8 +/- 2.18 g/dl, total leukocyte count
(TLC) 8.8 +/- 13.6 * 109/l, platelet count was 82 +/- 95.7 * 109/l. Of total 170
(96%) were transfusion dependent. Refractory cytopenias with multilineage
dysplasia (RCMD) was the most common world health organization (WHO) category.
Karyotype was done in 98 (55%) patients out of which 44 (45%) had abnormal
karyotype, complex karyotype (CK) was most commonly observed in 12 (12.2%)
followed by monosomy 7 in 7 (7.1%). CONCLUSIONS: We found younger median age at
diagnosis, higher mean TLC and no significant history of recurrent infections. CK
and monosomy 7 carry bad prognostic implications and early disease transformation
to acute myeloid leukemia (AML). Monosomy 7 being associated with bad overall
survival, such patients must be identified early with close clinical follow up
and offered stem cell transplant. This is the largest cohort of patients of MDS
evaluated for baseline clinical and cytogenetic characteristics in our country.
PMID- 28491139
TI - Traction using a clip-with-line is a preferred method for trainees in performing
esophageal endoscopic submucosal dissection: an animal model study.
AB - BACKGROUND: The optimal operative process of esophageal endoscopic submucosal
dissection (ESD), especially for the beginners, is not established. In this
study, the clip-with-line method, the tunneling method and the conventional
method for esophageal ESD were compared in a training course on live pigs.
METHODS: 15 trainee endoscopists were randomized into three groups, the clip-with
line method group, the tunneling method group, and the conventional method group.
Each trainee performed four esophageal ESDs on live pigs with one of the
specified methods, assisted by a senior endoscopist. The procedural time and
speed, the en bloc resection rates, adverse events, and self-completion rates
were recorded, and learning curves were drawn. RESULTS: The procedural time in
the clip-with-line group was significantly shorter than those in the tunneling
and the conventional method group (47.4 +/- 9.0 min versus 67.0 +/- 15.1 min and
67.0 +/- 11.8 min, p = 0.000). The clip-with-line method had the lowest rates of
perforation and muscle layer injury among the three methods. The en bloc
resection rates and self-completion rates were similar among the three groups.
Learning curves analysis showed the clip-with-line method was the easiest one for
the trainees to master. CONCLUSIONS: The clip-with-line method shortened
procedural time for trainees, and was associated with lower rates of adverse
events. This method is preferred for endoscopists in their learning periods for
esophageal ESD.
PMID- 28491140
TI - Tryptase mast cell density, protease-activated receptor-2 microvascular density,
and classical microvascular density evaluation in gastric cancer patients
undergoing surgery: possible translational relevance.
AB - BACKGROUND: Mast cells (MCs) can stimulate angiogenesis, releasing several
proangiogenic cytokines stored in their cytoplasm. In particular, MCs can release
tryptase, a potent in vivo and in vitro proangiogenic factor via protease
activated receptor-2 (PAR-2) activation and mitogen-activated protein kinase
(MAPK) phosphorylation. Nevertheless, no data are available concerning the
relationship among tryptase MC density (TMCD), endothelial cells (ECs) positive
to PAR-2 microvascular density (PAR-2-MVD) and classical MVD (C-MVD) in gastric
cancer (GC) angiogenesis. METHODS: In this study, we analyzed the correlation of
TMCD, PAR-2-MVD, C-MVD with each other and with the main clinicopathological
features in GC patients who underwent surgery. A series of 77 GC patients with
stage T2-3N2-3M0 (classified by the American Joint Committee on Cancer for
Gastric Cancer, 7th edition) were selected and then underwent surgery. RESULTS:
Tumour tissue samples were evaluated by mean of immunohistochemistry and image
analysis methods in terms of numbers of TMCD, PAR-2-MVD and C-MVD. A significant
correlation between the TMCD, PAR-2-MVD and C-MVD groups with each other was
found by Pearson t-test analysis (r ranged from 0.64 to 0.76; p value ranged from
0.02 to 0.03). There was no other significant correlation between the above
parameters and clinicopathological features. CONCLUSIONS: Our in vivo preliminary
data suggest that TMCD and PAR-2-MVD may play a role in GC angiogenesis and they
could be further evaluated as a target of antiangiogenic therapy.
PMID- 28491141
TI - Universal molecular screening does not effectively detect Lynch syndrome in
clinical practice.
AB - BACKGROUND: Lynch syndrome (LS) due to an inherited damaging mutation in mismatch
repair (MMR) genes comprises 3% of all incident colorectal cancer (CRC).
Molecular testing using immunohistochemistry (IHC) for MMR proteins is a
recommended screening tool to identify LS in incident CRC. This study assessed
outcomes of population-based routine molecular screening for diagnosis of LS in a
regional center. METHODS: We conducted a prospective, consecutive case series
study of universal IHC testing on cases of resected CRC from September 2004
December 2013. Referred cases with abnormal IHC results that attended a familial
cancer clinic were assessed according to modified Bethesda criteria (until 2009)
or molecular criteria (from 2009). RESULTS: 1612 individuals underwent resection
for CRC in the study period and had MMR testing by IHC. Of these, 274 cases
(16.9%) exhibited loss of expression of MMR genes. The mean age at CRC diagnosis
was 68.1 years (+/- standard deviation 12.7) and the mean age of those with an
IHC abnormality was 71.6 (+/- 11.8). A total of 82 (29.9%) patients with an
abnormal result were seen in a subspecialty familial cancer clinic. Patients aged
under 50 (p = 0.009) and those with loss of MSH6 staining (p = 0.027) were more
likely to be referred and to attend. After germ-line sequencing, 0.6% (10 of 82)
were identified as having a clinically significant abnormality. A further eight
probands with pathogenic germ-line mutations were identified from other referrals
to the service over the same time period. CONCLUSIONS: While technically
accurate, the yield of 'universal' IHC in detecting new Lynch probands is limited
by real-world factors that reduce referrals and genetic testing. We propose an
alternative approach for universal, incident case detection of Lynch syndrome
with 'one-stop' MMR testing and sequencing.
PMID- 28491142
TI - Current challenges in the treatment of severe Clostridium difficile infection:
early treatment potential of fecal microbiota transplantation.
AB - Fecal microbiota transplantation (FMT) is a very effective treatment for
recurrent Clostridium difficile infection (CDI). Less is known about the
application of FMT as a curative treatment of severe or complicated CDI. In this
review, we present and discuss evidence supporting the curative use of FMT in
severe or complicated CDI. We performed a literature search in PubMed and Embase
for studies on the curative use of FMT in severe or complicated CDI. In addition,
we describe a patient with severe CDI not responding to initial antibiotic
treatment, who was successfully treated with curative FMT. We found 23 reports
(12 case reports; 11 case series) about FMT as treatment for severe or
complicated CDI. The patients described all had severe or complicated CDI, did
not respond to conventional CDI antibiotic treatment and received FMT as last
resort treatment. Patients were treated with (sequential) FMT, whether or not
followed by additional antibiotic treatment for CDI. FMT, with or without
additional antibiotic CDI treatment, appears to be a promising curative treatment
option in patients with severe and complicated CDI, or only complicated CDI, who
do not respond sufficiently to conventional antibiotic treatment. Treatment with
FMT should be considered in these patients before proceeding to emergency bowel
surgery.
PMID- 28491144
TI - Clinical effectiveness and toxicity of second-line irinotecan in advanced gastric
and gastroesophageal junction adenocarcinoma: a single-center observational
study.
AB - BACKGROUND: Randomized clinical trials showed improved overall survival (OS) of
advanced gastroesophageal adenocarcinoma (GEA) patients treated with second-line
taxane or irinotecan. However, most data on irinotecan efficacy in this setting
come from large Asian trials. We retrospectively analyzed clinical effectiveness
and toxicity of irinotecan in a cohort of patients with advanced GEA treated in
our department. METHODS: Advanced GEA patients who received at least one cycle of
second-line irinotecan were eligible for inclusion. Irinotecan was administered
every 3 weeks at an initial dose of 250 mg/m2 of body surface area with
subsequent gradual (every 50 mg/m2) dose escalation up to 350 mg/m2, in the case
of good treatment tolerance. OS was estimated using the Kaplan-Meier method. A
multivariate Cox regression analysis was used to examine the association between
clinical and laboratory parameters and survival. RESULTS: A total of 48 patients
were identified. Median OS was 6.2 months [95% confidence interval (CI): 3.9
7.6]. In multivariate analysis, age < 65 years, baseline total lymphocyte count
(TLC) < 1500/ul and presence of peritoneal metastases were associated with
shorter OS. Most adverse events were grade 1-2 and included: anemia (52.3%),
leukocytopenia (40.9%), neutropenia (59.1%), nausea (25.0%), vomiting (31.8%),
diarrhea (31.8%), anorexia (29.5%) and fatigue (43.2%). Febrile neutropenia
occurred in three patients (6.8%). Nine patients (20.5%) experienced a toxicity
grade 3-4 of any kind. CONCLUSIONS: This retrospective analysis confirms clinical
effectiveness and manageable toxicity of second-line irinotecan in an unselected
cohort of advanced GEA patients. Age < 65 years, baseline TLC < 1500/ul and
presence of peritoneal metastases were independent prognostic factors associated
with shorter OS.
PMID- 28491143
TI - Probiotic engineering: towards development of robust probiotic strains with
enhanced functional properties and for targeted control of enteric pathogens.
AB - There is a growing concern about the increase in human morbidity and mortality
caused by foodborne pathogens. Antibiotics were and still are used as the first
line of defense against these pathogens, but an increase in the development of
bacterial antibiotic resistance has led to a need for alternative effective
interventions. Probiotics are used as dietary supplements to promote gut health
and for prevention or alleviation of enteric infections. They are currently used
as generics, thus making them non-specific for different pathogens. A good
understanding of the infection cycle of the foodborne pathogens as well as the
virulence factors involved in causing an infection can offer an alternative
treatment with specificity. This specificity is attained through the
bioengineering of probiotics, a process by which the specific gene of a pathogen
is incorporated into the probiotic. Such a process will subsequently result in
the inhibition of the pathogen and hence its infection. Recombinant probiotics
offer an alternative novel therapeutic approach in the treatment of foodborne
infections. This review article focuses on various strategies of bioengineered
probiotics, their successes, failures and potential future prospects for their
applications.
PMID- 28491145
TI - Combination of metformin and curcumin targets breast cancer in mice by
angiogenesis inhibition, immune system modulation and induction of p53
independent apoptosis.
AB - BACKGROUND: The effects of metformin (MET) and curcumin (CUR) single treatments
have been tested against breast cancer; however, their combination has not been
explored. Here, we evaluated the antitumor activity of MET and CUR combination
against breast cancer in mice. MATERIALS AND METHODS: The antiproliferative
activity of single and combined treatments against breast cancer cell lines was
determined. Vascular endothelial growth factor (VEGF) and Trp53 expression was
examined in EMT6/P cells. In vivo studies were carried out by inoculating BALB/c
mice with EMT6/P cells and examining tumor growth and apoptosis induction in
tumor sections. Furthermore, serum levels of different cytokines and
transaminases and creatinine were measured to detect the immune response and
toxicity, respectively. RESULTS: The combination treatment exhibited the highest
effects against tumor proliferation and growth. It significantly reduced VEGF
expression, induced Trp53 independent apoptosis, triggered Th2 immune response
and showed no toxicity. CONCLUSION: The combination can be a potential
therapeutic option to treat breast cancer. However, further testing is needed to
measure the exact serum levels of MET and CUR and to further explain the obtained
results.
PMID- 28491146
TI - PARP inhibitors in ovarian cancer: evidence, experience and clinical potential.
AB - Inhibitors of poly(ADP-ribose) polymerase (PARP) are considered one of the most
active and exciting new therapies for the treatment of ovarian cancer. The
anticancer activity of PARP inhibitors is based on the DNA repair vulnerability
of many ovarian cancer cells, and multiple mechanisms of action of PARP
inhibitors have been identified. As single agents, PARP inhibitors have
demonstrated their greatest activity in ovarian cancer cells that harbor
mutations in BRCA genes. Additionally, recent phase III studies have shown that
single-agent PARP inhibitor activity extends beyond BRCA-related cancers and can
benefit patients with ovarian cancers that do not have known BRCA mutations,
especially when clinical characteristics such as platinum sensitivity and high
grade serous histology are present. PARP inhibitors have also been combined with
chemotherapy, however, overlapping myelosuppression observed with PARP inhibitor
and chemotherapy combinations has hampered development of these combinations.
Contrariwise, PARP inhibitor and biologic agent combinations, specifically
antiangiogenic agents, appear well tolerated and show promising activity in both
BRCA mutated (BRCAm) and BRCA wild-type (BRCAwt) cancers. Currently, multiple
clinical trials are underway examining the antitumor activity of PARP inhibitor
combination therapy.
PMID- 28491147
TI - A clinical guide to the management of genitourinary symptoms in breast cancer
survivors on endocrine therapy.
AB - There is increasing attention and concern about managing the adverse effects of
adjuvant endocrine therapy for women with early breast cancer as the side effects
of therapy influence compliance and can impair quality of life (QoL). Most side
effects associated with tamoxifen (TAM) and aromatase inhibitors (AIs) are
directly related to estrogen deprivation, and the symptoms are similar to those
experienced during natural menopause but appear to be more severe than that seen
in the general population. Prolonged estrogen deprivation may lead to atrophy of
the vulva, vagina, lower urinary tract and supporting pelvic structures,
resulting in a range of genitourinary symptoms that can in turn lead to pain,
discomfort, impairment of sexual function and negatively impact on multiple
domains of QoL. The genitourinary side effects may be prevented, reduced and
managed in most cases but this requires early recognition and appropriate
treatment. We provide an overview of practical clinical approaches to
understanding the pathophysiology and the management of genitourinary symptoms in
postmenopausal women receiving adjuvant endocrine therapy for breast cancer.
PMID- 28491148
TI - Moving beyond vascular endothelial growth factor-targeted therapy in renal cell
cancer: latest evidence and therapeutic implications.
AB - Renal cell cancer (RCC) continues to be among the most lethal malignancies in the
USA. Introduction of anti-vascular epidermal growth factor receptor tyrosine
kinase inhibitors over a decade ago resulted in improvement in disease outcomes,
but further development of new therapies largely stagnated for many years. More
recently, a better understanding of disease biology and treatment-resistance
patterns has led to a second renaissance in drug development, with the anti
programmed cell death protein 1 immune checkpoint inhibitor, nivolumab, paving
the way for additional therapies entering clinical trial testing in the treatment
of RCC.
PMID- 28491150
TI - Dynamic silencing of somatic L1 retrotransposon insertions reflects the
developmental and cellular contexts of their genomic integration.
AB - BACKGROUND: The ongoing mobilization of mammalian transposable elements (TEs)
contributes to natural genetic variation. To survey the epigenetic control and
expression of reporter genes inserted by L1 retrotransposition in diverse
cellular and genomic contexts, we engineered highly sensitive, real-time L1
retrotransposon reporter constructs. RESULTS: Here we describe different patterns
of expression and epigenetic controls of newly inserted sequences retrotransposed
by L1 in various somatic cells and tissues including cultured human cancer cells,
mouse embryonic stem cells, and tissues of pseudofounder transgenic mice and
their progeny. In cancer cell lines, the newly inserted sequences typically
underwent rapid transcriptional gene silencing, but they lacked cytosine
methylation even after many cell divisions. L1 reporter expression was reversible
and oscillated frequently. Silenced or variegated reporter expression was
strongly and uniformly reactivated by treatment with inhibitors of histone
deacetylation, revealing the mechanism for their silencing. By contrast, de novo
integrants retrotransposed by L1 in pluripotent mouse embryonic stem (ES) cells
underwent rapid silencing by dense cytosine methylation. Similarly, de novo
cytosine methylation also was identified at new integrants when studied in
several distinct somatic tissues of adult founder mice. Pre-existing L1 elements
in cultured human cancer cells were stably silenced by dense cytosine
methylation, whereas their transcription modestly increased when cytosine
methylation was experimentally reduced in cells lacking DNA methyltransferases
DNMT1 and DNMT3b. As a control, reporter genes mobilized by piggyBac (PB), a DNA
transposon, revealed relatively stable and robust expression without apparent
silencing in both cultured cancer cells and ES cells. CONCLUSIONS: We hypothesize
that the de novo methylation marks at newly inserted sequences retrotransposed by
L1 in early pre-implantation development are maintained or re-established in
adult somatic tissues. By contrast, histone deacetylation reversibly silences L1
reporter insertions that had mobilized at later timepoints in somatic development
and differentiation, e.g., in cancer cell lines. We conclude that the cellular
contexts of L1 retrotransposition can determine expression or silencing of newly
integrated sequences. We propose a model whereby reporter expression from somatic
TE insertions reflects the timing, molecular mechanism, epigenetic controls and
the genomic, cellular and developmental contexts of their integration.
PMID- 28491152
TI - Temporal profile of PM10 and associated health effects in one of the most
polluted cities of the world (Ahvaz, Iran) between 2009 and 2014.
AB - Ahvaz, Iran ranks as the most polluted city of the world in terms of PM10
concentrations that lead to deleterious effects on its inhabitants. This study
examines diurnal, weekly, monthly and annual fluctuations of PM10 between 2009
and 2014 in Ahvaz. Health effects of PM10 levels are also assessed using the
World Health Organization AirQ software. Over the study period, the mean PM10
level in Ahvaz was 249.5 ug m-3, with maximum and minimum values in July (420.5
ug m-3) and January (154.6 ug m-3), respectively. The cumulative diurnal PM10
profile exhibits a dominant peak between 08:00-11:00 (local time) with the lowest
levels in the afternoon hours. While weekend PM10 levels are not significantly
reduced as compared to weekdays, an anthropogenic signature is instead observed
diurnally on weekdays, which exhibit higher PM10 levels between 07:00-17:00 by an
average amount of 14.2 ug m-3 as compared to weekend days. PM10 has shown a
steady mean-annual decline between 2009 (315.2 ug m-3) and 2014 (143.5 ug m-3).
The AirQ model predicts that mortality was a health outcome for a total of 3777
individuals between 2009 and 2014 (i.e., 630 per year). The results of this study
motivate more aggressive strategies in Ahvaz and similarly polluted desert cities
to reduce the health effects of the enormous ambient aerosol concentrations.
PMID- 28491153
TI - Estrogen receptor-positive primary squamous cell carcinoma of the breast.
AB - Pure primary squamous cell carcinoma of the breast (SCCB) represents around 0.1%
of breast carcinomas. Diagnosis requires independence from adjacent skin without
metastatic disease. SCCB is often large at presentation with nonspecific
mammographic and ultrasound findings. It is typically hormone receptor negative
and aggressive. Mastectomy and adjuvant chemotherapy is the most common
treatment, although treatment guidelines are not well established. We present a
case of pure primary SCCB detected by high risk screening mammogram and treated
with breast conserving surgery, chemotherapy, and radiation. We discuss clinical,
radiologic, and pathologic findings.
PMID- 28491151
TI - Methylation of DIRAS1 promotes colorectal cancer progression and may serve as a
marker for poor prognosis.
AB - BACKGROUND: DIRAS1 is a new member of the Ras gene family. It was described as a
potential tumor suppressor in human glioblastomas and esophageal cancer. The role
of DIRAS1 in colorectal cancer remains unclear. METHODS: To explore the
epigenetic changes and function of DIRAS1 in human colorectal cancer, we studied
ten colorectal cancer cell lines and 146 primary colorectal cancer samples and 50
matched adjacent samples using semi-quantitative reverse transcription PCR,
immunohistochemistry, methylation-specific PCR and bisulfite sequencing, western
blot, flow cytometry, and transwell assays. RESULTS: DIRAS1 expression was found
in DKO and HCT116 cells, while reduced expression was detected in LoVo, SW48,
LS180, and SW620 cells, and there was no expression detected in DLD1, HT29, RKO,
and SW480 cells. Complete methylation was found in the promoter region of DLD1,
HT29, RKO, and SW480 cells. Partial methylation was detected in LoVo, LS180,
SW48, and SW620 cells, and unmethylation was found in DKO and HCT116 cells. These
results indicate that promoter region methylation correlated with loss of/reduced
expression of DIRAS1. Re-expression of DIRAS1 was induced by 5-aza-2'
deoxycytidine, suggesting that the expression of DIRAS1 is regulated by promoter
region methylation. DIRAS1 was methylated in 47.3% (69/146) of primary colorectal
cancer samples, no methylation was found in non-cancerous colonic tissue samples.
Methylation of DIRAS1 was significantly associated with TNM stage (P < 0.05) and
short survival time (P = 0.0121). DIRAS1 induced apoptosis and inhibited cell
proliferation, migration, and invasion in colorectal cancer. Finally, DIRAS1
suppressed colorectal cancer cell xenograft growth in nude mice. CONCLUSIONS:
DIRAS1 is frequently methylated in human colorectal cancer and the expression of
DIRAS1 is regulated by promoter region methylation. Methylation of DIRAS1 is a
marker of poor prognosis in human colorectal cancer.
PMID- 28491154
TI - Spuriously aggressive features of a lactating adenoma prompting repeated
biopsies.
AB - We present an atypical presentation of a common pregnancy-related breast mass, a
lactating adenoma with imaging and pathologic correlation. The patient presented
with a rapidly enlarging left breast mass associated with skin changes and severe
pain in the perinatal period. Core biopsies were considered discordant, and the
patient went on to surgical excision for the definitive diagnosis of an infarcted
lactating adenoma. The symptoms of infarction may obscure the diagnosis of common
entities and result in additional evaluation.
PMID- 28491155
TI - Focal angiomatosis of the breast with MRI and histologic features.
AB - Angiomatosis of the breast is an extremely rare, benign vascular lesion. This is
a diagnostic challenge, given the limited number of cases reported in the
literature. Additionally, due to similar features of the more common malignant
vascular tumor, angiosarcoma familiarity with angiomatosis in the differential
diagnosis is important. We present a case of angiomatosis of the breast in a 28
year-old female. The lesion presented as an incidental enhancing mass on computed
tomography scan initially and subsequent mammogram and ultrasound studies did not
show a correlate. Next, magnetic resonance imaging demonstrated an enhancing
correlate for which magnetic resonance imaging biopsy and subsequent excisional
biopsy demonstrated angiomatosis of the breast.
PMID- 28491157
TI - Infracardiac type total anomalous pulmonary venous return with obstruction and
dilatation of portal vein.
AB - Total anomalous pulmonary venous return (TAPVR), also known as total anomalous
pulmonary venous connection, is a congenital cardiovascular malformation that
presents itself in the neonatal period, with cyanosis and tachypnea. There are 4
types of TAPVR with the mixed type being the least common. Any type of TAPVR may
be associated with obstruction as result of flow redirection through the liver
parenchyma before it may return to the heart, but infracardiac is the most common
one. We report a case of a 10-hour-old female, with a mixed (cardiac and
infracardiac) TAVPR with obstruction, that showed drainage to the coronary sinus
and the portal vein, as the other classic findings in TAVPR, made with computed
tomography angiography and echocardiogram. The patient was taken to surgical
repair, but unfortunately died during the procedure because of multiple
complications.
PMID- 28491156
TI - Primary lung carcinoid metastatic to the breast.
AB - Lung carcinoid tumors account for approximately 2% of lung cancers, with 10% of
the tumors represented by the atypical type. While atypical carcinoids are
metastatic to intrathoracic lymph nodes in approximately half of the cases on the
initial presentation, distant metastases are seen in only 20% of the patients and
are found most frequently in bones, liver, adrenal glands, and brain. We present
a case of an unusual metastatic disease to the breast in 51-year-old female who
developed a new breast mass 2 years after left lower lobectomy due to atypical
carcinoid tumor. Atypical pulmonary carcinoid metastases to the breast are
exceptionally uncommon, yet they are important considerations for appropriate
management, especially with an anamnesis of this neoplasm.
PMID- 28491158
TI - An unusual cause of atrial fibrillation in a young active duty soldier.
AB - Coronary artery fistula (CAF) is an abnormality in which the coronary artery has
an anomalous connection with a venous structure such as the coronary sinus or
atrium. CAF is usually congenital, but may be acquired. The prevalence in the
general population is low with many asymptomatic and discovered incidentally.
When symptomatic, CAF may present with dyspnea, decreasing functional capacity,
and/or arrhythmia. We report a case of a young otherwise healthy active duty male
with progressive symptoms of dizziness and exertional fatigue with paroxysmal
atrial fibrillation. An electrically negative, but symptomatically positive
stress test led to further workup with coronary computed tomography angiogram,
which unexpectedly revealed large coronary fistulas between the aneurysmal right
coronary artery and coronary sinus and the dilated left circumflex artery with
probable collateralization to the coronary sinus. Cardiac magnetic resonance
imaging and cardiac catheterization supported these findings and demonstrated no
evidence of significant shunting.
PMID- 28491159
TI - Huge idiopathic pulmonary artery aneurysm.
AB - A pulmonary artery aneurysm is an uncommon anomaly. The clinical manifestations
are mostly nonspecific, and management is controversial. We report a case of a 67
year-old woman with a main pulmonary artery aneurysm who did not take surgical
intervention. Subsequently, there was no increase in size for 3 years.
PMID- 28491160
TI - Asymptomatic left ventricular hemangioma.
AB - Cardiac hemangiomas are very rare benign neoplasms that are usually asymptomatic.
Although there are often found incidentally during echocardiography, other
imaging modalities such as computed tomography, magnetic resonance imaging, and
coronary angiography are needed to establish a diagnosis. Surgical excision is
therefore recommended to confirm the diagnosis and avoid potential complications.
We report a case of asymptomatic cardiac hemangioma that was discovered
incidentally during echocardiography.
PMID- 28491161
TI - Ruptured superficial femoral artery aneurysm: a case report.
AB - A 96-year-old male presented with left lower extremity pain, swelling, and
vascular compromise. Computed tomographic angiography revealed an actively
rupturing distal superficial femoral artery aneurysm. The patient underwent
prompt aneurysm excision with graft interposition and had a successful
postoperative outcome. Our case illustrates the critical role of imaging in
establishing a definitive diagnosis and preventing mortality.
PMID- 28491162
TI - Ectopic mediastinal parathyroid adenoma localized with four-dimensional CT: a
case report.
AB - We present a case of an ectopic mediastinal parathyroid adenoma in a 58-year-old
male patient. We show how different imaging modalities were successfully used to
reach a diagnosis. We particularly focus on the role of four-dimensional CT scan
in preoperative localization of ectopic adenomas and discuss how diverse imaging
modalities can be integrated in the workup of ectopic parathyroid adenomas.
PMID- 28491163
TI - Pulmonary inflammatory myofibroblastic tumor: report of 2 cases with radiologic
pathologic correlation.
AB - Inflammatory myofibroblastic tumor is a rare benign tumor that affects most
commonly children and young adults. In the lung, it comprises less than 1% of all
neoplasms. The authors describe the clinical, radiological, and pathologic
features of 2 cases of incidentally discovered pulmonary inflammatory
myofibroblastic tumors.
PMID- 28491164
TI - Spinal subarachnoid and subdural hematoma presenting as a Brown-Sequard-like
myelopathy following minor trauma in a patient on dabigatran etexilate.
AB - Dabigatran etexilate is a relatively new anticoagulant from the class of direct
thrombin inhibitors which is administered orally and does not require routine
blood work monitoring. Dabigatran may be attractive to both clinicians and
patients because of both its convenience and efficacy; however, clinical
complications are still being elucidated. Here, we present a previously
unreported case of spinal subarachnoid and subdural hematoma presenting as a
Brown-Sequard-like myelopathy in a patient after minor trauma in the setting of
Dabigatran anticoagulation.
PMID- 28491165
TI - Carbon dioxide angiography and arterial embolization could successfully control
postpartum uterine hemorrhage for the patient with hypersensitivity to iodine
compound.
AB - Transcatheter arterial embolization has become a common management option for
intractable postpartum uterine hemorrhage. Iodinated contrast agents are commonly
used for embolotherapy but cannot be used in patients with renal dysfunction or
iodine allergy. A 37-year-old woman spontaneously delivered a healthy girl but
developed severe postpartum uterine hemorrhage, probably due to placenta accrete.
Contrast-enhanced computed tomography revealed extravasation of the iodinated
contrast agent into the uterine cavity. The patient subsequently developed
allergic reaction to this agent. After recovery from the allergic reaction with
appropriate treatment, we performed carbon dioxide angiography and found that the
extravasation originated from the right uterine artery. Embolization of the right
internal iliac artery was performed, and hemostasis was verified. Based on this
experience, we suggest carbon dioxide angiography and arterial embolization can
be used for treating intractable postpartum hemorrhage in patients with iodinated
contrast media allergy or renal dysfunction.
PMID- 28491166
TI - Toothpick meningitis.
AB - A 66-year-old male with a history of hypertension, back pain, diverticulosis and
anal fistula presents with acute onset syncopal episodes, worsening back pain,
and altered mental status. The patient exhibited considerable leukocytosis but
was hemodynamically stable. CT imaging of the head revealed a gas pattern in the
posterior fossa and velum interpositum. CT imaging of the abdomen and pelvis
revealed a needle-like foreign body traversing the left sacrum to the sigmoid
colon. A lumbar puncture revealed meningitis. Flexible sigmoidoscopies were
performed without successful visualization of the foreign body. An explorative
laparoscopy was successfully performed, enabling retrieval of what was determined
to be a wooden toothpick. The patient remained hemodynamically stable with
persistent altered mental status and was eventually discharged after completion
of antibiotics on day 47 of hospitalization. This case illustrates a rare
complication of ingesting a sharp foreign body that was identified by CT of the
brain and abdomen/pelvis with successful surgical repair.
PMID- 28491167
TI - Disappearing portal venous gas in acute pancreatitis and small bowel ischemia.
AB - We report an usual case of hepatic portal venous gas (HPVG) in the setting of
acute pancreatitis and small bowel ischemia. Interestingly, the HPVG disappeared
within 2 hours of the original computed tomography scan, despite the patient
having small bowel ischemia. The patient had a complicated clinical course, dying
62 days postadmission. This case highlights that HPVG in setting of acute
pancreatitis and small bowel ischemia has a very high morbidity and mortality,
requiring early detection and aggressive surgical management.
PMID- 28491169
TI - Submucosal esophageal hematoma precipitated by chronic idiopathic
thrombocytopenic purpura.
AB - Submucosal esophageal hematoma is an uncommon clinical entity. It can occur
spontaneously or secondary to trauma, toxins, medical intervention, and in this
case, coagulopathy. Management of SEH is supportive and aimed at its underlying
cause. This article reports an 81-year-old male patient with chronic idiopathic
thrombocytopenic purpura and hypertension that develops a submucosal esophageal
hematoma.
PMID- 28491168
TI - Serous cystadenocarcinoma of the spleen.
AB - The commonly seen primary malignant neoplasms of the spleen are angiosarcoma and
lymphoma. We present a case of serous cystadenocarcinoma of the spleen. It was
presumed to be originated from dropped nonmalignant ovarian tissue, which was
accidentally implanted to the splenic surface during hysterectomy and bilateral
salpingooophorectomies for torsion of right fallopian tube 9 and half years ago
and transformed into serous cystadenocarcinoma later. Computed tomography
demonstrated a multilocular predominantly cystic tumor with internal soft tissue
components in the spleen.
PMID- 28491170
TI - High-grade transitional cell carcinoma masquerading as a xanthogranulomatous
pyelonephritis and perinephric abscess.
AB - Xanthogranulomatous pyelonephritis (XGPN) is an atypical long-term pyelonephritis
with destruction of renal parenchyma and a long-term inflammatory infiltrate of
macrophages. Reported presentations of transitional cell carcinoma (TCC) are
different. A 73-year-old woman presented with loin pain, prostration, and fever.
Computed tomography scan revealed poor cortical enhancement of the kidney, but
some of the images bore resemblance to the characteristic "bear's paw" sign,
consistent with XGPN with a 7-cm perinephric collection. She was provisionally
diagnosed as severe acute pyelonephritis, possibly XGPN, with abscess. In view of
the poor clinical condition, decision was made to perform nephrectomy. Histology
revealed a G3pT4 high grade TCC with perineural and vascular invasion and
reactive xanthogranulomatous inflammatory response. There are few reports of
concomitant XGPN and TCC affecting the kidney. However, there has not been any
mention of XGPN and TCC presenting as acute pyelonephritis and perinephric
abscess so far.
PMID- 28491171
TI - Transverse mobility of pelvic kidney causing left lower extremity deep venous
thrombosis.
AB - A case of May-Thurner-like syndrome was found to be a result of a pelvic kidney
compressing the left common iliac vein. Cross-sectional imaging demonstrated
transverse mobility of the pelvic kidney which has not been described previously.
The ectopic kidney's mobility resulted in intermittent venous compression. In a
patient with recurrent lower extremity deep venous thrombosis and a pelvic
kidney, the possibility of movement of the kidney resulting in venous compression
needs to be considered.
PMID- 28491172
TI - Acquired uterine arteriovenous fistula following dilatation and curettage: an
uncommon cause of vaginal bleeding.
AB - Dysfunctional uterine bleeding is a common presentation of women in the emergency
department. We describe the case of a 33-year-old female who presented with
intermittent spotting due to an acquired uterine AVF. The patient underwent a
transvaginal pelvic ultrasound as well as a CT angiogram. The patient was treated
conservatively and elected to undergo uterine artery embolization in an effort to
preserve fertility. She successfully delivered a healthy baby boy at 39-week
gestation via an emergent caesarian section due to a prolapsed umbilical cord 17
months after undergoing the uterine artery embolization.
PMID- 28491173
TI - Radiographically occult pulmonary metastases from gestational trophoblastic
neoplasia.
AB - Gestational trophoblastic neoplasia (GTN) is a spectrum of diseases including
partial and complete hydatidiform moles, placental site trophoblastic tumor, and
choriocarcinoma. One of the most important considerations is recognition of the
possibility of GTN after molar pregnancy or even normal pregnancy. It is common
practice to use chest x-ray for the detection of pulmonary metastasis. Computed
tomography imaging of the lungs is ordered if lung lesions are noted on chest x
rays. However, understanding the limitations of chest x-rays is important for
detecting smaller pulmonary lesions. We present a patient with GTN and pulmonary
metastasis after having received 2 negative chest x-rays.
PMID- 28491174
TI - Diagnosis of abnormally invasive posterior placentation: the role of MR imaging.
AB - Abnormally invasive placentation is becoming more common with a recent increase
in cesarean sections and maternal age, among other risk factors. Ultrasonography
is the first line-imaging, but it can be difficult to diagnose when limiting
factors are present. Failure to recognize this serious placental abnormality
precludes us from making the appropriate plan for the delivery and consequently
can lead to fatal results. In this report, we present a case in which magnetic
resonance imaging was used to diagnose posterior placenta increta missed by
multiple sonographic examinations in a patient with previous myomectomies, and we
also include a review of the literature on this topic. It is our conclusion that
magnetic resonance imaging is superior to sonography to diagnose abnormally
invasive placentation in cases of posterior placenta previa and high pretesting
probability.
PMID- 28491175
TI - MRI characteristics of primary fallopian tube choriocarcinoma: a case report.
AB - Tubal choriocarcinoma is uncommon, and its magnetic resonance imaging
characteristics have not yet been reported. In this report, a 39-year-old woman
presented with irregular painless vaginal bleeding and a palpable left lower
abdominal lump for 2 months following 6 weeks' amenorrhea and positive urine
pregnancy test. Her serum beta-human chorionic gonadotropin value was
significantly increased. Ultrasound revealed a left adnexal mass, which showed no
blood flow signal on Color doppler flow imaging. A further MR examination showed
a well-defined cystic-solid mass with cystic component accounting for a large
proportion in the left lower abdomen. The solid part with mixed signals resembled
a honeycomb. Finally, the left tubal choriocarcinoma was confirmed by pathology.
When the solid parts of cystic-solid mass appeared as "honeycomb appearance" and
the ovaries were normal by magnetic resonance imaging, together with typical
symptoms and significantly elevated beta-human chorionic gonadotropin values,
radiologists should feel more confident in suspecting tubal choriocarcinoma and
reporting it on their differential.
PMID- 28491176
TI - Nontraumatic urinary bladder rupture presenting as renal pseudo-failure and
ascites.
AB - A 24-year-old man, with past medical history significant only for nocturnal
enuresis until the age of 12 years, presented to the emergency department with
acute abdominal pain after an episode of difficulty with micturition in the
middle of the night. On presentation, physical examination was suggestive of
ascites and laboratories revealed an elevated serum creatinine of 1.88 mg/dL. He
was subsequently found to have a ruptured bladder, without any inciting trauma,
which required surgical repair. His only surgical history is an unknown,
apparently urologic, surgery when he was 11-12 years old. The patient's unique
presentation prompts discussion of bladder rupture and its manifestations, the
role of clinical information in informing imaging protocol, and the importance of
sagittal images in identifying pathology.
PMID- 28491177
TI - Incidentally discovered well-differentiated retroperitoneal liposarcoma with
inguinal canal herniation: report of 2 cases.
AB - Well-differentiated retroperitoneal liposarcomas are slow growing and low-grade
tumors, reaching usually huge size before being symptomatic and so diagnosed,
therefore with increase of the surgical risk and of the probability of
dedifferentiation. Inguinal location of these tumors is unusual and rarely
diagnosed.
PMID- 28491178
TI - Ossifying fibroma: an uncommon differential diagnosis for T2-hypointense
sinonasal masses.
AB - Ossifying fibroma is a benign fibro-osseous lesion that occurs most commonly in
the mandible of female patients. In rare cases, it affects the nasal cavity. The
magnetic resonance imaging features may vary depending on the amount of fibrous
and bony tissue in its composition. In these tumors, T2-hypointensity is a
feature described in the peripheral ossified areas of the lesion, but it may
present diffusely, especially when the degree of ossification is extensive. In
this scenario, this particular characteristic on T2-weighted imaging is
superimposable to the commonly described appearance of other lesions, such as non
Hodgkin's lymphoma, melanoma, and other sinonasal neoplasms with high cellularity
and high nucleocytoplasmic ratio. In the present study, we report a case of
ossifying fibroma of the nasal cavity that presented as a diffusely and
homogeneously T2-hypointense mass, a finding that may cause difficulty in the
differential diagnosis with other expansive sinonasal lesions.
PMID- 28491179
TI - Transhepatic embolization of a congenital intrahepatic portosystemic shunt for
the treatment of hepatic encephalopathy in a noncirrhotic patient using Amplatzer
vascular plug device.
AB - A 73-year-old male with no history of liver disease was hospitalized for
weakness, confusion, ataxia, and new onset hepatic encephalopathy with
hyperammonemia. After management with lactulose and rifaximin, his symptoms
persisted, and he underwent transjugular liver biopsy. Biopsy showed normal
liver, but a portosystemic shunt was incidentally identified on postbiopsy
venogram. The patient underwent occlusion of the shunt with two Amplatzer
vascular plugs and four Nester coils. Following embolization, the patient's
symptoms resolved completely. Our case reports one of the oldest adults to
present with symptoms from a congenital portosystemic shunt. Congenital
portosystemic shunts can be considered in patients with new onset hepatic
encephalopathy in the absence of underlying liver disease. Prognosis after
embolization of congenital portosystemic shunt is great, and embolization may
result in full reversal of symptoms.
PMID- 28491180
TI - Transbiliary intravascular ultrasound-guided diagnostic biopsy of an inaccessible
pancreatic head mass.
AB - Percutaneous image-guided biopsies of pancreatic malignancies may prove
challenging and nondiagnostic due to a variety of anatomic considerations. For
patients with complex post-surgical anatomy, such as a Roux-en-Y gastric bypass,
diagnosis via endoscopic ultrasound with fine-needle aspiration may not be
possible because of an inability to reach the proximal duodenum. This report
describes the first diagnostic case of transbiliary intravascular ultrasound
guided biopsy of a pancreatic head mass in a patient with prior Roux-en-Y gastric
bypass for which a diagnosis could not be achieved via percutaneous and
endoscopic approaches. Transbiliary intravascular ultrasound-guided biopsy
resulted in a diagnosis of pancreatic adenocarcinoma, allowing the initiation of
chemotherapy.
PMID- 28491181
TI - TIPS performed in a patient with complete portal vein thrombosis.
AB - Portal vein thrombosis is common in cirrhotic patients and results in increased
morbidity and mortality. Transjugular intrahepatic portosystemic shunt (TIPS)
creation is a well-established therapy for refractory variceal bleeding and
refractory ascites in patients who do not tolerate repeated large volume
paracentesis. Experience and technical improvements have led to improved TIPS
outcomes that have encouraged an expanded application. Complete portal vein
thrombosis has come a long way from being a contraindication to an indication for
TIPS procedure. As experience and technology have evolved, the ultrasound
guidance transvenous access of portal vein from the hepatic vein help in overall
higher success rate of performing the TIPS procedure and reducing the procedure
related complications.
PMID- 28491182
TI - Aortoenteric fistulae temporization and treatment: lessons learned from a
multidisciplinary approach to 3 patients.
AB - Aortoenteric fistulae are life-threatening conditions characterized by abnormal
communications between the aorta and gastrointestinal tract. Aortoenteric
fistulae may be characterized by the triad of bleeding, abdominal pain, or a
pulsatile abdominal mass. Although hemorrhage is the most common presentation, it
does not always occur; thus, patients may present with nonspecific symptoms.
Computed tomography angiography findings suggestive of aortoenteric fistulae
include ectopic gas within or adjacent to the aorta, discontinuity of the aortic
wall, bowel wall thickening, and extravasation of contrast into the bowel.
Endovascular treatments include retrograde balloon occlusion of the aorta and
stent-graft deployment as well as coil, fibrin, and glue embolization of the
fistulous tract. This report describes 3 cases of aortoenteric fistulae
temporized and treated by interventional radiology and vascular and cardiac
surgery at a single institution in an effort to increase awareness of this
important clinical condition.
PMID- 28491183
TI - Tine after tine: a varied approach to the removal of a long-standing IVC filter.
AB - Inferior vena cava filters are important tools used to help prevent life
threatening pulmonary embolisms in hospitalized patients with contraindications
to pharmacological prophylactic anticoagulation. This is a case report of a
patient who had an inferior vena cava filter placed after a traumatic subdural
hematoma. He made a complete recovery but was lost to follow-up until he
presented 1825 days after filter deployment with abdominal pain discovered to be
from penetration of the filter tines outside the lumen and into adjacent
structures. We describe a case complicated by fibrotic tine entrapment with
penetration to surrounding structures and discuss the technical approach used to
free and eventually remove the long-standing filter.
PMID- 28491184
TI - Feasibility of transfemoral hepatic vein/wedged portal venous pressure
measurement in total artificial heart.
AB - The development of technology and limitation of numerous ventricular assist
devices has increased usage of the total artificial heart (TAH) for mechanical
circulatory support. A primary important feature of TAH is that it is one of the
few mechanical circulatory support devices that provides biventricular support.
As the number of patients with TAH rises, spreading awareness about the device in
the interventional radiology community is important.
PMID- 28491185
TI - Extra-adrenal pheochromocytoma at the organ of Zuckerkandl: a case report and
literature review.
AB - Pheochromocytomas and paragangliomas are tumors that occur in characteristic
locations and are commonly detected on imaging studies. A correct diagnosis is
important because of differences in associated neoplasms, risk for malignancy,
and need for genetic testing. In addition, associated complications, including
death, can be avoided if appropriately recognized and treated. Here, we report a
rare case of an extra-adrenal paraganglioma of the organ of Zuckerkandl.
PMID- 28491186
TI - Quantifying spasticity in individual muscles using shear wave elastography.
AB - Spasticity is common following stroke; however, high subject variability and
unreliable measurement techniques limit research and treatment advances. Our
objective was to investigate the use of shear wave elastography (SWE) to
characterize the spastic reflex in the biceps brachii during passive elbow
extension in an individual with spasticity. The patient was a 42-year-old right
hand-dominant male with history of right middle cerebral artery-distribution
ischemic infarction causing spastic left hemiparesis. We compared Fugl-Meyer
scores (numerical evaluation of motor function, sensation, motion, and pain),
Modified Ashworth scores (most commonly used clinical assessment of spasticity),
and SWE measures of bilateral biceps brachii during passive elbow extension. We
detected a catch that featured markedly increased stiffness of the brachialis
muscle during several trials of the contralateral limb, especially at higher
extension velocities. SWE was able to detect velocity-related increases in
stiffness with extension of the contralateral limb, likely indicative of the
spastic reflex. This study offers optimism that SWE can provide a rapid, real
time, quantitative technique that is readily accessible to clinicians for
evaluating spasticity.
PMID- 28491187
TI - Giant cell tumor of the tendon seath of the tendinous insertion in pes anserinus.
AB - A 56-year-old woman with a palpable lump in the medial surface of her left knee
was referred for diagnostic workup with magnetic resonance imaging. The lesion
was pathogically confirmed to be a giant cell tumor of the tendon seath. The MR
features of the lesion are presented.
PMID- 28491188
TI - Brace yourself: an unusual case of knee pain, an extradigital glomangioma of the
knee.
AB - The differential diagnosis for knee pain is extensive. Glomus tumors comprise
approximately 1.6% of soft-tissue tumors in the extremities. Classic subungual
tumors occur more frequently in women, whereas ectopic locations are more common
in men. Unusual locations include the stomach; lungs; trachea; bones; intestines;
fallopian tubes; and intraneural, neuromal, and intravenous locations. We present
the case of a 50-year-old man with a 12-year history of enlarging right knee mass
found to be a glomangioma. This case report discusses the incidence,
presentation, imaging characteristics, histology, and management of glomus tumors
of the knee.
PMID- 28491189
TI - Asymmetric bone mineral density in the bilateral femoral necks due to gluteal
implants: a case report.
AB - Interpreting asymmetric bone mineral density in the bilateral hips on dual energy
x-ray absorptiometry requires investigation into the potential causes, both real
and artifactual. Silicone gluteal implants have been reported to cause abnormally
elevated bone mineral density. We report a case of abnormally low bone mineral
density in a patient with bilateral gluteal implants. This is likely due to
patient positioning and inability of the computer to identify the superior margin
of the proximal femur and the femoral neck.
PMID- 28491190
TI - Pyogenic brain abscess with atypical features resembling glioblastoma in advanced
MRI imaging.
AB - Differentiation between infectious and neoplastic brain processes is crucial for
treatment planning. Advanced magnetic resonance imaging techniques, such as
diffusion, perfusion, susceptibility weighted imaging, and magnetic resonance
spectroscopy, enhance the imaging differences between these two pathologies.
However, despite the utilization of these advanced techniques, the pathologic
process may be confound by atypical findings. Here, we report a case of an
autistic patient with multiple brain lesions with diffusion weighted imaging,
susceptibility weighted imaging, and perfusion patterns resembling features of a
multicentric glioblastoma, which were confirmed surgically, neuropathologically,
and bacteriologically as brain abscesses. We discuss the differentiation of these
different entities in the light of advanced magnetic resonance imaging
techniques.
PMID- 28491191
TI - Internal carotid artery dissection and pseudoaneurysm formation with resultant
ipsilateral hypoglossal nerve palsy.
AB - Craniocervical artery dissection is a potentially disabling condition caused by
an intimal tear allowing blood to enter and dissect the media in the cranial
direction which can occur spontaneously or as a result of trauma. When the
dissection extends toward the adventitia, it can form a protrusion from the
weakened vessel wall called a pseudoaneurysm, which may become a nidus for distal
thromboembolism or cause mass effect on adjacent structures. Accurate and prompt
diagnosis is critical as timely treatment can significantly reduce the risk of
complications such as stroke. Here, we present a case of cervical ICA dissection
and pseudoaneurysm formation causing mass effect with resultant compressive
ipsilateral hypoglossal nerve palsy.
PMID- 28491192
TI - A case report of spinal dural arteriovenous fistula: origins, determinants, and
consequences of abnormal vascular malformations.
AB - A spinal dural arteriovenous fistula is an abnormally layered connection between
radicular arteries and venous plexus of the spinal cord. This vascular condition
is relatively rare with an incidence of 5-10 cases per million in the general
population. Diagnosis of spinal dural arteriovenous fistula is differentiated by
contrast-enhanced magnetic resonance angiography or structural magnetic resonance
imaging, but a definitive diagnosis requires spinal angiography methods. Here, we
report a case of a 67-year-old female with a spinal dural arteriovenous fistula,
provide a pertinent clinical history to the case nosology, and discuss the
biology of adhesive proteins, chemotactic molecules, and transcription factors
that modify the behavior of the vasculature to possibly cause sensorimotor
deficits.
PMID- 28491193
TI - Indium-111 labeled leukocyte accumulation in extremity soft tissue sarcoma.
AB - Nuclear medicine labeled leukocyte whole-body scintigraphy is commonly used to
identify a source of infection in a patient with fever of unknown origin. White
blood cells can also localize to other sites of inflammation, including sometimes
tumors. A patient with a large myxofibrosarcoma in his left forearm was scanned
due to chronic low-grade fever and persistent leukocytosis. This case
demonstrates focal white blood cell activity in an extremity soft tissue sarcoma.
PMID- 28491194
TI - Leptomeningeal carcinomatosis and bilateral internal auditory canal metastases
from ovarian carcinoma.
AB - Ovarian cancer, a leading cause of death in women, typically spreads locally and
rarely metastasizes to the brain or seeds the leptomeninges. We present a case of
a 62-year-old woman with a history of treated ovarian cell carcinoma who
developed bilateral sensorineural deafness and right-sided facial weakness and on
imaging was found to have bilateral internal auditory canal (IAC) masses and
leptomeningeal carcinomatosis, pathologically proven by cerebrospinal fluid
cytology. We discuss her magnetic resonance imaging and positron emission
tomography-computed tomography findings and review the imaging characteristics of
IAC metastases. Finally, we review the literature on leptomeningeal
carcinomatosis from ovarian cancer and discuss the high incidence of bilateral
IAC metastases in patients with leptomeningeal carcinomatosis.
PMID- 28491195
TI - Pediatric jugular vein aneurysm (phlebectasia): report of two cases and review of
the literature.
AB - Jugular vein aneurysms are rare vascular abnormalities that are most commonly
encountered in the pediatric population. We report two separate cases in infants,
both of whom presented with enlarging neck masses and were found to have jugular
vein aneurysms. Diagnosis was established with duplex ultrasonography, computed
tomography angiography, digitally subtracted catheter venography, and magnetic
resonance imaging in one case and magnetic resonance imaging with magnetic
resonance angiography/magnetic resonance venography, gray scale ultrasonography,
and digital subtraction catheter venography in the other case. Both aneurysms
were treated by surgical resection.
PMID- 28491196
TI - Cerebral palsy and seizures in a child with tubulinopathy pattern dysgenesis and
focal cortical dysplasia.
AB - A 7-year-old boy with a history of spasticity, global developmental delay, and
seizures was given the general diagnosis of cerebral palsy at an early age.
Chromosomal array analysis performed at an outside center was normal. The
patient's family sought neurodevelopmental pediatric care at a new institution
following a move out of state. Electroencephalography confirmed abnormal
epileptogenic activity. Brain magnetic resonance imaging showed findings
consistent with a tubulin gene defect (tubulinopathy) and of focal cortical
dysplasia, as well as evidence of a remote occipital lobe injury. This case
report describes the various brain magnetic resonance findings suggestive of a
tubulin gene defect and raises the possibility of focal cortical dysplasia
manifesting as a result of tubulin dysfunction.
PMID- 28491197
TI - Traumatic rupture of a giant congenital splenic cyst presenting as peritonitis.
AB - Splenic cysts are uncommon, with large cysts and complications being rare. We
describe a 6-year-old patient who initially presented 1 day after falling onto
her abdomen at the playground with worsening abdominal pain and distention. An
ultrasound of the abdomen demonstrated free abdominal fluid in all four
quadrants. A subsequent contrast-enhanced computed tomography scan of the abdomen
and pelvis was performed which showed a large splenic cyst with open
communication to the peritoneal cavity. A congenital primary cyst was confirmed
on pathology after partial splenectomy was performed. Although the majority of
splenic cysts are asymptomatic, rupture can lead to acute peritoneal signs and
mimic other significant causes of abdominal pain such as viscous injury or acute
appendicitis.
PMID- 28491198
TI - Synovial osteochondromatosis in a 14-year-old boy with a history of Legg-Calve
Perthes disease.
AB - We describe a case of a 14-year-old boy with a history of Legg-Calve-Perthes
disease diagnosed at the age of 6 years and development of synovial
osteochondromatosis of the same hip joint 7 years later. Synovial
osteochondromatosis is very rare in children, and to the best of our knowledge,
only a single case of Legg-Calve-Perthes disease and secondary synovial
osteochondromatosis was described in the literature in a 35-year-old male, making
this the first reported case of Legg-Calve-Perthes disease with development of
synovial osteochondromatosis in a pediatric patient.
PMID- 28491199
TI - Emergent sclerotherapy of a newborn with expanding lymphatic malformation causing
respiratory distress.
AB - The present report describes a case of acute airway obstruction in a newborn
caused by an expanding hemorrhagic macrocystic lymphatic malformation (LM), which
was successfully treated with emergent decompression and interventional radiology
guided sclerotherapy. The use of sclerotherapy for macrocystic LMs has been well
described for various indications. The urgent interventional treatment obviated
the need for a tracheostomy. This case describes the rapid diagnosis and use of
sclerotherapy in a large expanding macrocystic LM.
PMID- 28491200
TI - Aneurysmal angiosarcoma associated with vascular graft revealed by 18F-FDG-PET
imaging.
AB - We report a rare case of vascular graft-associated aneurysmal angiosarcoma by 18F
Fluorodeoxyglucose (FDG) positron emission tomography (PET). An 81-year-old male
patient, with a prior history of graft interposition 1 year previously, was
referred to 18F-FDG-PET because of an inflammatory syndrome of unknown origin.
FDG-PET images revealed a particular pattern of intense circular uptake within
the arterial wall (SUVmax = 10) in a popliteal aneurysm and, additionally, a
large hypermetabolic mass centered by the graft. Remote hypermetabolisms in lung
nodules and pleural thickenings were also detected. The diagnosis of angiosarcoma
was ascertained through histopathological analysis of surgical samples.
Development of an aneurysmal angiosarcoma at the site of a vascular graft is a
rare entity, often misdiagnosed. 18F-FDG-PET appears to be useful in its
detection with a PET pattern of intense circular uptake within the arterial wall.
Such finding should lead to the search for distant metastasis.
PMID- 28491201
TI - The advantage of iron-containing fiducial markers placed with a thin needle for
radiotherapy of liver cancer in terms of visualization on MRI: an initial
experience of Gold Anchor.
AB - Radiotherapy for liver malignancy is increasing due to advances in radiotherapy
technique. Visualization of the tumor as well as fiducial markers is essential.
To see if improved visibility exists on computed tomography (CT) and magnetic
resonance imaging (MRI), we evaluated an iron-containing fiducial marker. A
patient with hepatocellular carcinoma and a patient with cholangiocarcinoma were
enrolled. Pain caused by placement of marker and the best MRI sequence for
visualization of both the fiducial marker as well as the liver tumor on MRI was
evaluated. CT was obtained in 2.5-mm thickness, and MRIs were obtained in eight
sequences (ie, T2-weighted image). 22G preloaded needles were used for marker
placement in both patients; this caused little pain during placement under local
anesthesia with xylocaine. No complication occurred in either patient. Both
markers and tumors were well visualized by the same MRI sequence. The iron
containing fiducial marker is safe and useful for detecting fiducial markers in
the liver and for registration using CT and MRI.
PMID- 28491202
TI - Just a mirage: heterotopic intrauterine and twin ectopic pregnancy mimicked by
mirror imaging on ultrasound.
AB - Heterotopic pregnancies are rare and are usually diagnosed by transvaginal
ultrasound. Despite the routine use of sonography in early pregnancy, artifact
created by mirror imaging can drastically and erroneously alter medical decision
making by interfering with image interpretation. A heterotopic pregnancy with a
single intrauterine gestation and twin left adnexal ectopic gestational sacs was
observed on ultrasound in a woman presenting with abdominal pain. During
laparoscopy, an ectopic pregnancy was not identified, and subsequent
intraoperative ultrasound reproduced the heterotopic pregnancy through
manipulation of bowel, confirming mirror image artifact. This phenomenon is
rarely seen in obstetric imaging; therefore, lack of awareness can lead to false
diagnosis of heterotopic pregnancy. Techniques to verify correct diagnosis should
be used to resolve potential mirror artifact before proceeding with surgical
management.
PMID- 28491203
TI - Traumatic lumbar vertebral ring apophysis fracture with disk herniation in an
adolescent.
AB - We present a case of a 15-year-old male with history of back pain and bilateral
lower limb radiculopathy due to fall. The magnetic resonance imaging scan showed
disc bulge at L2-L3 level causing compression on contained nerve roots. In this
case, computed tomography scan was indispensable for diagnosis and classification
of the vertebral apophyseal fracture and to guide appropriate further management.
Apophyseal ring fracture is an uncommon cause of back pain with radiculopathy in
adolescents and athletes. High degree of suspicion is necessary to differentiate
these injuries from disc herniation so as to further guide appropriate
conservative or surgical management. The common cause of back pain in this
population is related to musculoskeletal injuries. Lumbar disc herniation
contributes to negligible number of cases in this age group, as against that seen
in the adult population. An important and rare etiology to be considered for
these patients includes vertebral ring apophyseal fracture.
PMID- 28491204
TI - Being forced to become your own Doctor - Men who have Sex with Men's Experiences
of Stigma in the Tanzanian Healthcare System.
AB - OBJECTIVE: To acquire a deepened understanding of how stigma in healthcare
affects health-seeking behaviours of same-sex practising men in Tanzania.
METHODS: In-depth interviews with twelve men were conducted in Dar es Salaam,
2012. Data were interpreted through qualitative content analysis. RESULTS:
Narratives revealed that men's healthcare perceptions were shaped by previous
encounters, rumours in gay community, norms and legislation around homosexuality.
Fears of exposure aggravated men's possibilities of giving full anamnesis and
detached them from formal healthcare services. CONCLUSIONS: Stigma in healthcare
might lead to severe public health problems due to perceived exclusion from the
health system by sexual minorities.
PMID- 28491205
TI - Food Insecurity among American Indians and Alaska Natives: A National Profile
using the Current Population Survey-Food Security Supplement.
AB - Food insecurity increases the risk for obesity, diabetes, hypertension, and
cancer-conditions highly prevalent among American Indians and Alaska Natives
(AI/ANs). Using the Current Population Survey Food Security Supplement, we
analyzed the food insecurity trends of AI/ANs compared to other racial and ethnic
groups in the United States from 2000 to 2010. From 2000 to 2010, 25% of AI/ANs
remained consistently food insecure and AI/ANs were twice as likely to be food
insecure compared to whites. Urban AI/ANs were more likely to experience food
insecurity than rural AI/ANs. Our findings highlight the need for national and
tribal policies that expand food assistance programs; promote and support
increased access to healthy foods and community food security, in both rural and
urban areas; and reduce the burden of diet-related disparities on low-income and
racial/ethnic minority populations.
PMID- 28491206
TI - Effects From a Randomized Control Trial Comparing Researcher and School
Implemented Treatments With Fourth Graders With Significant Reading Difficulties.
AB - This study examined the effectiveness of a researcher-provided intervention with
4th-graders with significant reading difficulties. The intervention emphasized
multi-syllable word reading, fluent reading of high frequency words and phrases,
vocabulary, and comprehension. To identify the participants, 1,695 fourth grade
students were screened using the Gates MacGinitie Reading Test, and those whose
standard score was 85 or lower were included in the study (N=485). Participants
were randomly assigned (2:1) to receive either researcher-provided intervention
(n=324) or intervention provided by school personnel (business as usual, BAU)
(n=161). Findings revealed no statistically significant differences between
students in the researcher-provided intervention and BAU groups. Using effect
sizes as an indicator of impact, students in the researcher implemented treatment
generally outperformed students in the school implemented treatment (BAU).
Examining growth in standard scores, both groups made significant gains in
reading outcomes with standard score growth from pretest to posttest of 3
standard score points on decoding, 5 on fluency,, and 2.0 to 7 standard score
points on reading comprehension measures.
PMID- 28491207
TI - Giant laryngeal polyp: an unusual indication of tracheostomy.
PMID- 28491209
TI - [Post-traumatic vertebral dissection: MRI results].
PMID- 28491208
TI - Joint pain epidemiology and analgesic usage in Madagascar.
AB - INTRODUCTION: To describe the epidemiology of joint pains and document analgesics
usage in an African context. METHODS: Patients suffering from joint pain were
recruited from nine sites located in Antananarivo, Madagascar, including 6
hospital services and 3 clinics. Doctors collected information on the etiology
and characteristics of the patients' pain. Analgesics prescribed by these doctors
were also documented. RESULTS: In total, 400 patients were enrolled in the study
(52.5% women, mean age of 42.34 years +/- 17.7 [4-86]). Pain of mechanical type
was found in 260 participants, 65%; 95% CI [60.1% to 69.6%] and inflammatory type
pains in 128 cases 32%; 95% CI [27.5% to 36.9%]. Mixed pains were found in 12
patients (3%). The median duration of pain prior to the consultation was 6.5
days. The average pain intensity was 57.9 +/- 19.9 mm of a total of 100 mm
maximum on a visual analogue scale, VAS. The etiologies of mechanical type pains
were dominated by fracture, common low back pain and tendonitis. Arthrosis was
the dominant cause of inflammatory type pain, followed by rheumatoid arthritis
and gout. NSAIDs (74.5%) were the most frequently prescribed analgesics followed
by paracetamol (49.5%), weak opioids (23%) and corticosteroids (12.25%). Two
thirds of medical prescriptions (65.3%) were of combined analgesics. CONCLUSION:
These findings demonstrated that mechanical type pains were the main reason for
consultations for joint pain in these situations in Antananarivo, Madagascar. The
most frequently prescribed pain-relieving medications were NSAIDs, paracetamol,
weak opioids and corticosteroids. This descriptive study may be a useful starting
point for further epidemiological studies of pain in the African context.
PMID- 28491210
TI - [Surgical treatment of the humeral pallet fractures in adults].
AB - The treatment of humeral pallet fractures is mainly based on reconstruction
surgery with osteosynthesis. We collected the data of 40 patients with humeral
pallet fracture from our archives in the Department of Orthopaedics and
Traumatology at the Ibn Sina University Hospital, Rabat from january 2012 to
december 2014. The aim of our study was to highlight the clinical, therapeutic
and evolutionary features of these fractures as well as the challenges in
managing these complex fractures and in evaluating the results. There was a clear
male predominance (75% of cases) with an average age of 35 years. Etiologies were
dominated by road accidents (56%). All our patients had an emergency hospital
admissions and underwent surgery. Type C fracture, according to MULLER and
ALLGOWER (A.O) classification was the most frequent: 62.5% of cases. Associated
lesions were fairly frequent (52.5%) in polytraumas. All our patients underwent
surgery (100% of cases), via posterior border in 70% of cases. This procedure
included reduction and then osteosynthesis using a Lecestre-type plate in 82.5%
of the cases. Our results were good and average in 85.5% of cases, according to
literature data. The management of this type of fracture is based on perfect
anatomic reduction, a solid assembly which should allow an early reeducation
resulting in good functional result.
PMID- 28491212
TI - An unusual cause of chronic low back pain: ochronosis.
PMID- 28491211
TI - [Rickettsiosis associated with cerebral infarction: a new case study].
AB - Mediterranean spotted fever (MSF) is a rickettsiosis of the spotted fever group
caused by rickettsia conorii. This zoonosis is benign but it can be complicated
by severe neurological impairment (hence its severity). We report the case of a
49-year old patient hospitalized in the Department of Dermatology for
rickettsiosis, who suffered from right massive hemiplegia of brutal onset.
Magnetic resonance angiography (MRA) of the brain showed deep left sylvian
fissure ischemic stroke. The diagnosis of conorii-type rickettsiosis has been
retained based on the aspect of skin lesions and on positive sierologic testing
with the indirect immunofluorescence method. Evolution was favorable under anti
biotherapy (Doxycycline and fluoroquinolone). Cerebral infarction, exceptionally
reported in the framework of neurological manifestations of rickettsioses, is a
complication that shouldn't be underestimated especially when etiologic
assessment (cardiovascular in particular) is negative.
PMID- 28491213
TI - [The diffuse plexiform neurofibroma of the left thigh in a patient aged 78 years
in dermatological environment in Bamako].
PMID- 28491214
TI - Prescribing pattern of psychotropic medications in child psychiatric practice in
a mental referral hospital in Botswana.
AB - INTRODUCTION: There is a growing preference for psycho-pharmacological therapy
over non-pharmacological care. The prescription pattern and the choice of
psychotropic medications vary in different settings. Whilst newer agents and
rational prescribing are favored in the more specialized settings, the pattern
remains unclear in less specialized units, largely due to lack of data. The aims
were to conduct a treatment audit in the only mental referral hospital in
Botswana, which is a non-specialized child and adolescent care setting and see
how it conforms to best practice. METHODS: A retrospective audit which involved
the extraction of socio-demographic and clinical information from the records of
patients who were <= 17 years and seen from January 1, 2012-July 31, 2016.
RESULTS: A total of 238 files were used for this report. Mean age (SD) was 12.41
(4.1) years. Of the 120 (50.4%) patients who had pharmacological intervention,
only 85(70.8%) had monotherapy. The most commonly prescribed psychotropic agents
were antipsychotics (40%). Off-label use of antipsychotics and polypharmacy were
31.2% and 29.2% respectively. CONCLUSION: The level of conformity to standard
practice in terms of psychotropic prescribing in our setting is consistent with
the reports from developed countries where more specialized care ostensibly
exists. Further studies will be necessary to determine the scope of psychotropic
use.
PMID- 28491215
TI - Clinical outcomes of posterior spinal stabilization with rigid vertical strut and
spinal process wires (the Adeolu's technique) in a developing country.
AB - INTRODUCTION: Conventional instrumentation for spinal stabilization is beyond the
reach of many patients in developing countries. A low-cost and easily-available
method of spinal stabilization using vertical struts and spinal process wires
(Adeolu's technique) was recently introduced in Nigeria. We describe the clinical
outcomes of a prospective series of patients managed using the technique.
METHODS: From 2011 to 2012, we performed posterior spinal stabilization in
eighteen patients using the technique. Primary outcomes were radiological
evidence of rigid stabilization and mobilization without restrictions referable
to the procedure in the immediate post-operative period. Implant rotation,
migration, back-out, fracture, wound infection, worsening neurological status and
need for implant removal were secondary measures. Overall patient satisfaction
was assessed using a five-point Likert scale. The average follow-up period was
11.6 months. RESULTS: The average age of the patients was 45.8 years. Trauma with
unstable spinal fractures (11), spondylosis (5), and thoracic extra-dural tumour
(2) were the indications for surgery. The average number of spinal levels
stabilized was 6. All patients had satisfactory primary outcomes. Implant
rotation occurred in 3 patients (16.7%). There was no case of implant migration,
back-out or fracture. Superficial surgical site infection occurred in one
patient. There was no need to remove the implant in any subject and none had post
operative worsening of neurological status. The overall patient satisfaction was
good with 17 patients (94.4%) reporting "highly satisfied" or "satisfied" with
the surgical procedure. CONCLUSION: The technique offers utility in a wide range
of spinal pathologies and short-term clinical outcomes are good.
PMID- 28491216
TI - [Isolated tuberculous trochanteritis].
PMID- 28491217
TI - [Guillain Barre syndrome and diabetic acido-ketotic decompensation during
pregnancy: a case report and review of the literature].
AB - A 27-year-old pregnant woman was admitted to the resuscitation department with
severe spontaneous acute ketoacidosis as early symptom of type 1 diabetes. The
patient underwent resuscitation and insulin treatment with good clinical and
biological evolution. On day 4, the patient had polyradiculoneuritis
characterised by acute onset. Additional emergency examinations were negative.
Lumbar cytopunction showed albuminocytologic dissociation. Electromyogram
confirmed the diagnosis of Guillain Barre syndrome (GBS). The patient was treated
with veinoglobulin and underwent physical rehabilitation. A dramatic improvement
in neurological signs was noted. With regard to pregnancy, the patient aborted a
week after being diagnosed with GBS. The association of GBS with ketotic
decompensation is rare. Indeed, a few cases have been reported in the literature.
This association during pregnancy was never described, hence the originality of
this case study.
PMID- 28491218
TI - Bacterial agents of the discharging middle ear among children seen at the
University of Nigeria Teaching Hospital, Enugu.
AB - INTRODUCTION: Discharging middle ear continues to be one of the commonest
problems seen in the developing world. There is an ever growing need to carry out
studies periodically to determine the common bacterial agents responsible for
discharging otitis media and their antibiotic sensitivity especially in set-ups
characterized with minimal laboratory services. The study sought to determine the
common bacterial agents causing discharging middle ear among children presenting
at the University of Nigeria Teaching Hospital, Enugu and their sensitivity to
the commonly available antibiotics. METHODS: Middle ear swabs were collected from
100 children aged 1 month to 17 years at the Children Out-Patient and
Otorhinolaryngology Clinics of the University of Nigeria Teaching Hospital,
Enugu, Nigeria. The specimens were cultured for aerobic bacterial organisms and
their sensitivity determined. RESULTS: Among those with acute discharge,
Staphylococcal aureus was isolated in 31.3% and Proteus species in 25.0%. In
chronically discharging ears, Proteus Species dominated (39.1%), followed by
Staphylococcal aureus (28.3%). CONCLUSION: Staphylococcal aureus and Proteus
species were the commonest bacterial agents in acute and chronic otitis media
respectively. Most isolates showed high sensitivity to the fluoroquinolone
antibiotics.
PMID- 28491219
TI - [A non-EDTA-dependent pseudothrombocytopenia: about a case].
AB - Pseudothrombocytopenia is a rare phenomenon in laboratory explained by in vitro
agglutination of platelets. Microscopic examination of the peripheral blood smear
is of key importance to confirm the diagnosis and to avoid any inappropriate or
dangerous clinical and therapeutic decision. Its occurrence in a patient, under
treatment with heparin, raises the problem of differential diagnosis of heparin
induced thrombocytopenia. The aim of this study was to eliminate any confusion
between this purely artefactual phenomenon and heparin-induced thrombocytopenia.
PMID- 28491221
TI - Isolated tuberculosis of metacarpal bone in a 3 year-old child.
AB - Primary tuberculosis osteomyelitis of metacarpal bone is rare. The majority of
cases occur in children and young adults and there is difficulty in diagnosis
mainly in young children. We report a new case in children aged of 3 years,
presenting a swelling on the dorsal side of her right hand since 8 months. X-ray
showed an expansile, cystic and lytic lesion involving the little finger
metacarpal. Tuberculosis was confirmed on histological examination. No lesions in
lung parenchyma or lymphadenopathy were associated. Patient was successfully
managed by anti-tubercular drugs.
PMID- 28491220
TI - A primary intestinal lymphangiectasia hiding the diagnosis of pleural and
pericardial tuberculosis: a clinical observation.
AB - Primary intestinal lymphangiectasia (Waldmann's disease) is an exudative
enteropathy characterized by lymph leakage into the small bowel lumen leading to
hypoalbuminemia, hypogammaglobulinemia and lymphopenia (particularly T-cell). The
diagnosis is based on viewing the duodenal lymphangiectasia. A 20 years old
female patient, treated for a primary intestinal lymphangiectasia, has consulted
for anasarca. Etiological work-up reveals pleural and pericardial tuberculosis.
The clinical aggravation of an enteropathy, particularly in adulthood, requires a
search for a secondary etiology. Tuberculosis should be sought systematically.
PMID- 28491222
TI - [Intramedullary glioblastomas in the child: location and rare histologic type].
PMID- 28491223
TI - [Neuroendocrine carcinoma of the bladder: about 5 cases].
AB - Neuroendocrine carcinoma of the bladder is a rare histological entity,
characterized by the ability to metastasize quickly and associated with a poor
prognosis. The purpose of this study was to analyze the clinical, histological,
therapeutic and prognostic characteristics of neuroendocrine carcinoma of the
bladder. We conducted a retrospective study collecting data from the medical
records of 5 patients in the Department of Urology, at the Ibn Sina University
Hospital during the period between January 2008 and June 2015. The average age
was 63 years. Four males and one female were involved in the sudy. The
neuroendocrine carcinoma was pure in four cases and impure or associated with
urothelial component in one case. In two patients metastases were present at
initial diagnosis. In one case, cystectomy was performed followed by neoadjuvant
chemotherapy; chemoradiotherapy was performed in two cases and palliative
chemotherapy in the other two cases. The median survival was 10 months. Only one
patient was alive, with a follow-up period of 20 months. The management of
neuroendocrine carcinoma of the bladder is not standardized, several therapeutic
options have been proposed: surgery, radiation therapy and chemotherapy.
PMID- 28491224
TI - [Macrophage activation syndrome complicating family lymphohistiocytosis].
AB - Macrophage activation syndrome (MAS) is an anatomoclinic entity due to
inappropriate macrophage activation. It is a rare pathology, characterized by
clinical signs that are not very specific and by biological elements. Their
association must evoke the diagnosis. It can be classified as primary or
secondary, its prognosis is still unclear. We report the case of a 3-year and 4
month-old infant admitted to our department with primary MAS in order to remind
clinicians the importance of suspecting primary cause in specific situations.
PMID- 28491225
TI - ?
PMID- 28491226
TI - [A rare etiology of horse tail syndrome: neuro-aggressive vertebral hemangioma].
PMID- 28491227
TI - [A rare cause of spinal cord compression: spontaneous spinal epidural hematoma].
PMID- 28491228
TI - [Survival among chronic hemodialysed patient in Cameroon].
AB - INTRODUCTION: Haemodialysis is the only renal replacement therapy available in
Cameroon; 95% of patients has received subsidies by the State since 2002 and the
number of dialysis centers is growing. However, since the opening of the first
center in 1990, there are no data on survival in chronic dialysis patients.
METHODS: We conducted a multicenter prospective cohort study of 15 months in
order to assess mortality rates and factors that influence the survival of
chronic hemodialysis patients in Cameroon. RESULTS: We followed 197 patients of
whom 109 were incident patients. The average age was 47,97+/- 13.19 years and 55%
were male. The mean duration of dialysis in prevalent patients was 12.5 months.
The mortality rate was 57,58%, 50% of which occurred the first 3 months and
abandonment rate was 8.6%. Uremia and catheter-related sepsis were the main
causes of death. At a median follow up of 15 months, the overall survival was
30.77%, with an average duration of life of 8 months. Prevalent patients,
patient's place of residence where the dialysis center is located, nonfamily
management, predialysis follow up > 3 months, blood cholesterol when patient
first started on dialysis> 1.5g/l, a mental test score > 25 were associated with
a better survival. CONCLUSION: In Cameroon, mortality rate in hemodialysis
patients is high, with a mean survival time of 8 months; most patients die within
the first 3 months.
PMID- 28491229
TI - [Anti-VEGF therapy for juxtafoveolar choroidal neovessels in people with high
myopia: about a case].
AB - Choroidal neovessels are a threatening complication of high myopia, accounting
for 5 to 10% of cases. They require immediate treatment because of their poor
prognosis. Anti-VEGF intravitreal injections are currently a new therapeutic
alternative far exceeding photodynamic therapy (PDT). Nevertheless, anti-VEGF
treatment algorithm for this type of neovessels remains a matter of discussion
among the authors. The purpose of this study was to highlight the difficulties in
managing these neovessels and to discuss the Anti-VEGF therapeutic regimen to
follow.
PMID- 28491230
TI - Lung hemorrhage and brain stroke following fatal viper (cerastes cerastes) bite.
PMID- 28491231
TI - Monoarthritis of the knee revealing tabetic arthropathy.
PMID- 28491232
TI - [Cavernoma in the fourth ventricle].
PMID- 28491233
TI - Branchial cleft cyst: a case report.
PMID- 28491234
TI - Knowledge and utilization of contraceptive devices among unmarried undergraduate
students of a tertiary institution in Kano State, Nigeria 2016.
AB - INTRODUCTION: Students in the universities mostly live independently from their
parents or guardians, some of them for the first time. This gives them freedom
and opportunity for high risk behavior such as unplanned and unprotected sex. The
results of such sexual experimentation may include unplanned and or unwanted
pregnancies that may lead to unsafe abortions and sexually transmitted infections
(STIs) including HIV/AIDS. Contraception has the potential to prevent unwanted
pregnancies, abortion, and STIs. This study aimed at assessing the general
knowledge on contraceptives, sexual practices, and level of utilization of
contraceptives devices among unmarried students of the Bayero University Kano.
METHODS: We did an institutional based cross-sectional descriptive study. We
administered a pretested, self-administered, structured questionnaire to randomly
selected unmarried undergraduate students of the institution. We analyzed data
using Microsoft Excel 2016 and Epi-info7. RESULTS: A total of 300 students were
interviewed. The median age for respondents was 23 years with an age range of 16
25 years. Male respondents made up 61.3% (184) while the females made up the
remaining 38.7% (116). Also, 158(47.33%) of respondents lived outside the school
campus, while 158(52.67%) lived in the school hostels. Knowledge on contraception
was 87.7% among respondents with internet (91%) and media (89.3%) as the
commonest sources of knowledge. Proportion of sexually active students was
10.67%, while prevalence of contraceptive utilization among sexually active
students was 15.63%. About 8(25%) had their sexual debut at < 16years of age,
22(68.75%) at ages between 16-20years, and 4(12.5%) above 20years of age. All
sexually active respondents practice vaginal sex. Most sexual debuts were planned
(44.75 %) and with friends (86.4%), and they occurred between the ages of 16
20years age group in 70.3% of respondents. CONCLUSION: Even though knowledge on
contraceptive used was high among the respondents, utilization of contraceptives
among sexually active students was low, thus creating a window for possible
unintended and unwanted pregnancies among these group of students.
PMID- 28491235
TI - A systematic review of physical activity policy recommendations and interventions
for people with mental health problems in Sub-Saharan African countries.
AB - INTRODUCTION: There is a need for interventions to address the escalating mental
health burden in Sub-Saharan Africa (SSA). Implementation of physical activity
(PA) within the rehabilitation of people with mental health problems (PMHP) could
reduce the burden and facilitate recovery. The objective of the current review
was to explore (1) the role of PA within mental health policies of SSA countries,
and (2) the current research evidence for PA to improve mental health in SSA.
METHODS: We screened the Mental Health Atlas and MiNDbank for mental health
policies in SSA countries and searched PubMed for relevant studies on PA in PMHP
in SSA. RESULTS: Sixty-nine percent (=33/48) of SSA countries have a dedicated
mental health policy. Two of 22 screened mental health policies included broad
physical activity recommendations. There is clear evidence for the role of PA in
the prevention and rehabilitation of depression in SSA. CONCLUSION: Despite the
existing evidence, PA is largely a neglected rehabilitation modality in the
mental health care systems of SSA. Continued education of existing staff,
training of specialized professionals and integration of PA for mental health in
public health awareness programs are needed to initiate and improve PA programs
within the mental health care systems of SSA.
PMID- 28491236
TI - Self-referral patterns among federal civil servants in oyo state, South-Western
Nigeria.
AB - INTRODUCTION: Primary health care is widely accepted as the first point of care;
yet, individuals requiring healthcare engage in self-referrals to higher levels
of care thereby by-passing primary care. Little is known of the extent to which
self-referrals are carried out when care is needed. This study thus sought to
determine the prevalence of self-referral, its patterns and factors influencing
self-referrals amongst federal civil servants in Southwestern Nigeria. METHODS: A
cross-sectional study was carried out among 300 federal civil servants who were
interviewed using validated and pre-tested interviewer-administered semi
structured questionnaires. Data was analyzed using univariate and Chi-square test
at level of significance set at P <0.05. RESULTS: Mean age of the respondents was
39.96 +/- 9.1 years with majority being married (80.7%); 90.7% completed tertiary
education (and 76.7 % were middle grade (7-12) level officers. Most (60.0%) of
the respondents had ever engaged in self-referral. Malaria was the commonest
health problem (39.7%) for self-referral to secondary or tertiary facilities.
Desire for quality service (35.7%) and competent staff (35.2%) were the commonest
reasons for self-referral to a higher level of health care. More female
respondents (76.0%) compared to male respondents (64.0%) significantly engaged in
self-referral (p = 0.02, X2 = 5.14). Respondents having good knowledge of
referral practices engaged less in self-referral compared to those with poor
knowledge. (p = 0.02, X2 = 5.43). CONCLUSION: Having good knowledge of referral
practices and being male are positively associated with referral practices.
Creating awareness and improving knowledge on referral practices with special
emphasis on women population are desirable strategies for encouraging the use of
primary health care as first of point of contact with health systems.
PMID- 28491237
TI - Potential of Lichen Compounds as Antidiabetic Agents with Antioxidative
Properties: A Review.
AB - The advancement in the knowledge of potent antioxidants has uncovered the way for
greater insight in the treatment of diabetic complications. Lichens are a rich
resource of novel bioactive compounds and their antioxidant potential is well
documented. Herein we review the antidiabetic potential of lichens which have
received considerable attention, in the recent past. We have correlated the
antidiabetic and the antioxidant potential of lichen compounds. The study shows a
good accordance between antioxidant and antidiabetic activity of lichens and
points out the need to look into gathering the scarce and scattered data on
biological activities for effective utilization. The review establishes that the
lichen extracts, especially of Parmotrema sp. and Ramalina sp. have shown
promising potential in both antidiabetic and antioxidant assays. Ubiquitous
compounds, namely, zeorin, methylorsellinate, methyl-beta-orcinol carboxylate,
methyl haematommate, lecanoric acid, salazinic acid, sekikaic acid, usnic acid,
gyrophoric acid, and lobaric acid have shown promising potential in both
antidiabetic as well as antioxidant assays highlighting their potential for
effective treatment of diabetic mellitus and its associated complications. The
available compilation of this data provides the future perspectives and highlight
the need for further studies of this potent herbal source to harvest more
beneficial therapeutic antidiabetic drugs.
PMID- 28491238
TI - Inhibition of miR-302 Suppresses Hypoxia-Reoxygenation-Induced H9c2 Cardiomyocyte
Death by Regulating Mcl-1 Expression.
AB - MicroRNAs play important roles in cell proliferation, differentiation, and
apoptosis, and their expression influences cardiomyocyte apoptosis resulting from
ischemia-induced myocardial infarction. Here, we determined the role of miR
expression in cardiomyocyte apoptosis during hypoxia and reoxygenation. The rat
cardiomyocyte cell line H9c2 was incubated for 3 h in normal or hypoxia medium,
followed by reoxygenation for 24 h and transfection with a miR-302 mimic or
antagomir. The effect of miR-302 on myeloid leukemia cell-differentiation protein
1 (Mcl-1) expression was determined by western blot, real-time polymerase chain
reaction, and luciferase reporter assays, with cell viability assays. We observed
that miR-302 expression was elevated by hypoxia/reoxygenation injury and
increased further or decreased by transfection of the miR-302 mimic or miR-302
antagomir, respectively. Additionally, elevated miR-302 levels increased
apoptosis-related protein levels and cardiomyocyte apoptosis, and luciferase
reporter assays revealed miR-302 binding to the Mcl-1 mRNA 3' untranslated
region. Our findings suggested that miR-302 overexpression aggravated
hypoxia/reoxygenation-mediated cardiomyocyte apoptosis by inhibiting
antiapoptotic Mcl-1 expression, thereby activating proapoptotic molecules.
Furthermore, results indicating cardiomyocyte rescue from hypoxia/reoxygenation
injury following treatment with miR-302 antagomir suggested that miR-302
inhibition might constitute a therapeutic strategy for protection against
cardiomyocyte apoptosis during hypoxia/reoxygenation injury.
PMID- 28491239
TI - Opuntia spp.: Characterization and Benefits in Chronic Diseases.
AB - Opuntia species have been used for centuries as food resources and in traditional
folk medicine for their nutritional properties and their benefit in chronic
diseases, particularly diabetes, obesity, cardiovascular diseases, and cancer.
These plants are largely distributed in America, Africa, and the Mediterranean
basin. Opuntia spp. have great economic potential because they grow in arid and
desert areas, and O. ficus-indica, the domesticated O. species, is used as a
nutritional and pharmaceutical agent in various dietary and value-added products.
Though differences in the phytochemical composition exist between wild and
domesticated (O. ficus-indica) Opuntia spp., all Opuntia vegetatives (pear,
roots, cladodes, seeds, and juice) exhibit beneficial properties mainly resulting
from their high content in antioxidants (flavonoids, ascorbate), pigments
(carotenoids, betalains), and phenolic acids. Other phytochemical components
(biopeptides, soluble fibers) have been characterized and contribute to the
medicinal properties of Opuntia spp. The biological properties of Opuntia spp.
have been investigated on cellular and animal models and in clinical trials in
humans, allowing characterization and clarification of the protective effect of
Opuntia-enriched diets in chronic diseases. This review is an update on the
phytochemical composition and biological properties of Opuntia spp. and their
potential interest in medicine.
PMID- 28491240
TI - High quality permanent draft genome sequence of Chryseobacterium bovis DSM
19482T, isolated from raw cow milk.
AB - Chryseobacterium bovis DSM 19482T (Hantsis-Zacharov et al., Int J Syst Evol
Microbiol 58:1024-1028, 2008) is a Gram-negative, rod shaped, non-motile,
facultative anaerobe, chemoorganotroph bacterium. C. bovis is a member of the
Flavobacteriaceae, a family within the phylum Bacteroidetes. It was isolated when
psychrotolerant bacterial communities in raw milk and their proteolytic and
lipolytic traits were studied. Here we describe the features of this organism,
together with the draft genome sequence and annotation. The DNA G + C content is
38.19%. The chromosome length is 3,346,045 bp. It encodes 3236 proteins and 105
RNA genes. The C. bovis genome is part of the Genomic Encyclopedia of Type
Strains, Phase I: the one thousand microbial genomes study.
PMID- 28491242
TI - Moving Forward.
PMID- 28491241
TI - Fifteen years of bone marrow mononuclear cell therapy in acute myocardial
infarction.
AB - In spite of modern treatment, acute myocardial infarction (AMI) still carries
significant morbidity and mortality worldwide. Even though standard of care
therapy improves symptoms and also long-term prognosis of patients with AMI, it
does not solve the critical issue, specifically the permanent damage of
cardiomyocytes. As a result, a complex process occurs, namely cardiac remodeling,
which leads to alterations in cardiac size, shape and function. This is what has
driven the quest for unconventional therapeutic strategies aiming to regenerate
the injured cardiac and vascular tissue. One of the latest breakthroughs in this
regard is stem cell (SC) therapy. Based on favorable data obtained in
experimental studies, therapeutic effectiveness of this innovative therapy has
been investigated in clinical settings. Of various cell types used in the clinic,
autologous bone marrow derived SCs were the first used to treat an AMI patient,
15 years ago. Since then, we have witnessed an increasing body of data as regards
this cutting-edge therapy. Although feasibility and safety of SC transplant have
been clearly proved, it's efficacy is still under dispute. Conducted studies and
meta-analysis reported conflicting results, but there is hope for conclusive
answer to be provided by the largest ongoing trial designed to demonstrate
whether this treatment saves lives. In the meantime, strategies to enhance the
SCs regenerative potential have been applied and/or suggested, position papers
and recommendations have been published. But what have we learned so far and how
can we properly use the knowledge gained? This review will analytically discuss
each of the above topics, summarizing the current state of knowledge in the
field.
PMID- 28491243
TI - Choledochal cyst in pregnancy.
AB - INTRODUCTION: Biliary diseases during pregnancy are not uncommon and are
frequently due to cholelithiasis. Choledochal cyst during pregnancy is rare. The
management of biliary pathologies during pregnancy poses a challenge as the
window of opportunity to carry out any interventions with minimal risk is small.
CASE REPORT: We report the case of a lady who was diagnosed with a large type I
choledochal cyst during the second trimester of pregnancy. Due to increasing
symptoms and recurrent cholangitis, she was managed with antibiotics and surgical
resection. She remained well and delivered a healthy baby boy. CONCLUSION:
Clinicians need to consider choledochal cyst as a differential in pregnant
patients presenting with upper abdominal fullness.
PMID- 28491244
TI - Diarrheagenic Escherichia coli pathotypes frequency in Khuzestan province of
Iran.
AB - BACKGROUND AND OBJECTIVES: Diarrheagenic Escherichia coli (DEC) is an emerging
agent among pathogens that causes diarrhea. Studies showed that diarrheagenic E.
coli such as enterohaemorrhagic E. coli (EHEC), enteroaggregative E. coli (EAEC),
enteropathogenic E. coli (EPEC), enteroinvasive E. coli (EIEC), enterotoxigenic
E. coli (ETEC), diffusely adhering E. coli (DAEC) and shiga toxin producing E.
coli (STEC) strains are among the most frequent causative agents in acute
diarrhea. The aim of this study was to determine the frequency of DEC pathotypes
in Khuzestan province. MATERIALS AND METHODS: Stool samples were collected from
patients with diarrhea in Khuzestan province of Iran. E. coli strains were
isolated using conventional culture and standard biochemical tests. The
polymerase chain reaction (PCR) technique was used to detect presence of
virulence genes, i.e; eae, stx1 and stx2 for EHEC, bfp and eae for EPEC, LT and
ST for ETEC, AA for EAEC, invE for EIEC, stx1 and stx2 for STEC. RESULTS:
Altogether, 200 stool samples were obtained from patients, of which 158 (79%)
were positive for E. coli. DEC was identified in 127 (63%) of stool samples,
which frequency of each pathotypes were as follows: atypical EPEC 49 (39%),
typical EPEC 1 (0.7%), STEC 50 (39.3%), ETEC 21 (16.3%), EAEC 5 (4.0%) and EIEC 1
(0.7%). Most frequent etiological agents of diarrhea in Khuzestan province of
Iran were STEC and EPEC. CONCLUSION: Our findings showed DEC had been agent of
diarrhea in Khuzestan. This finding provides evidence that effort should be made
to estimate the burden of infection by the etiological agent for better medical
approach and should raise notification about antibiotic resistance among
bacterial infection.
PMID- 28491246
TI - Significance of coagulase negative Staphylococcus from blood cultures: persisting
problems and partial progress in resource constrained settings.
AB - BACKGROUND AND OBJECTIVES: Coagulase negative Staphylococcus (CoNS) is frequently
isolated from blood cultures but their significance is difficult to interpret.
CoNS bacteria which are often previously dismissed as culture contaminants are
attracting greater importance as true pathogens in the past decades. Clinical
evaluation of these isolates suggests that although there is a relative increase
of CoNS associated bloodstream infections in recent years, the microorganisms
still remain the most common contaminants in blood cultures. The objective of
this study was to determine the significance of CoNS isolated from blood
cultures. MATERIALS AND METHODS: A retrospective study was conducted to evaluate
the rate of contamination in blood cultures in a tertiary care hospital. The
paired specimens of blood were cultured using conventional culture methods and
the isolates of coagulase negative staphylococci were identified by standard
methodology. Clinical data, laboratory indices, microbiological parameters and
patient characteristics were analyzed. RESULTS: Of 3503 blood samples, CoNS were
isolated from blood culture of 307 patients (8.76%). The isolates were reported
as true pathogens of bloodstream infections in only 74 out of 307 cases (24.1%).
In the vast majority, 212 of 307 (69.0%), they were mere blood culture
contaminants and reported as insignificant/contaminant. CONCLUSION: Determining
whether a growth in the blood culture is a pathogen or a contaminant is a
critical issue and multiple parameters have to be considered before arriving at a
conclusion. Ideally, the molecular approach is for the most part a consistent
method in determining the significant isolates of CoNS. However, in countries
with inadequate resources, species identification and antibiogram tests are
recommended when determining significance of these isolates.
PMID- 28491245
TI - Frequency evaluation of genes encoding siderophores and the effects of different
concentrations of Fe ions on growth rate of uropathogenic Escherichia coli.
AB - BACKGROUND AND OBJECTIVES: Bacteria need iron for growth and most of them can
actively acquire Fe ions using especial iron-chelating proteins which named
siderophores. We aimed to determine the frequencies of iucA, iroN and irp2 genes
in the uropathogenic Escherichia coli (UPEC) isolates. We also analyzed the
effects of siderophore genes beside iron supplements on growth rate of the
isolates. MATERIALS AND METHODS: Totally, 170 E. coli strains were isolated from
urinary tract infections and the presence of 3 siderophore genes were analyzed
using PCR among them. Three final concentrations of 0.1, 0.5 and 1 mMFe(II) and
Fe(III) ions were made in M9 broth medium. Inoculated cultures were incubated at
37 degrees C for 33 hours and bacterial density in the suspension was measured
with 1 hour intervals using spectrophotometer. RESULTS: The frequency of iucA,
iroN and irp2 genes among 170 UPEC isolates were 29 (17.1%), 52 (30.6%) and 116
(68.2%), respectively. In addition, Our findings showed that Fe(II) supplements
had significantly higher promoting effects on UPEC growth rate almost in all of
the three applied concentrations (0.1, 0.5 and 1 mM) compared to the control
group (P<0.0001). Differences between Fe(III) supplemented groups and the
controls were statistically significant when 1 mM concentration was added into
the medium (p<0.05). CONCLUSION: irp2 gene probably plays a major role in the
pathogenesis of UPEC strains. Promoting or inhibitory effects of iron on
bacterial growth mainly depend on the iron concentration in the culture medium
however different siderophores have different potentials for capturing and
assimilation of Fe ions by the bacteria, especially inside the host cell.
PMID- 28491247
TI - The antibacterial activity of methanolic Anacyclus pyrethrum and Pistacia
lentiscus L. extract on Escherichia coli.
AB - BACKGROUND AND OBJECTIVES: Antibiotic therapy is the main choice in treatment of
Escherichia coli induced infections. Using herbal medication is an alternative
choice in treatment of diseases. The aim of this study was to determine the
antibacterial activity of two traditionally used herbs in Iranian medicine,
Anacyclus pyrethrum and Pistacia lentiscus L., on Escherichia coli. MATERIALS AND
METHODS: The antibacterial effect of methanolic extract of Anacyclus pyrethrum
and Pistacia lentiscus L. were examined in disk diffusion and skipped wells
methods by measuring the diameter of inhibition zones around wells containing
different concentrations of extracts from (10-1000 mg/ml) using standard broth
macrodilution, method the MIC and MBC were defined. RESULTS: The methanolic
extract of Anacyclus pyrethrum from 300 to 1000 mg/ml and the methanolic extract
of Pistacia lentiscus L. from 30 to 1000 mg/ml showed antibacterial activity on
Escherichia coli. The MIC of Anacyclus pyrethrum and Pistacia lentiscus L.
methanolic based extract were 800 and 1000 mg/ml, respectively. The MBC was
achieved at 800 mg/ml for methanolic extract of Anacyclus pyrethrum and Pistacia
lentiscus L. CONCLUSION: The methanolic extract of Anacyclus pyrethrum and
Pistacia lentiscus L. have antibacterial effect on Escherichia coli bacteria.
This activity is dose-dependent.
PMID- 28491248
TI - The comparison of five low cost liquid formulations to preserve two phosphate
solubilizing bacteria from the genera Pseudomonas and Pantoea.
AB - BACKGROUND AND OBJECTIVES: Phosphorus is one of the low bioavailable
macroelements. Use of microorganisms in biofertilizers could release phosphorus
from insoluble compounds. Pseudomonas putida P13 and Pantoea agglomerans P5 are
well recognized for application as phosphate solubilizing bioinoculants and are
used as solid carrier based. Liquid bioinoculants are preferred for economizing
production process and longer shelf-life. MATERIALS AND METHODS: Five low cost
liquid formulations were examined. Formulations 1, 2 and 3, were phosphate
buffer, 0.2% and 0.5% KNO3 dissolved in phosphate buffer, respectively.
Formulation 4 was nutrient broth containing 4% glycerol and formulation 5 was
diluted nutrient broth containing 4% glycerol. Survival (cfu) and phosphate
solubilization index (SI) were evaluated after 3 months. RESULTS: Considering
strain P5, increase in KNO3 concentration decreased preserving ability. While
using KNO3 at 0.2% was accompanied with reaching maximum SI level. Overall, less
nutritious formulations (1 and 5) provided maximum preserving ability without
bioactivity loss. In the case of strain P13, maximum survival obtained in
formulations 2 and 3, whereas SI level decreased. Preserving ability in
formulations 1, 4 and 5 was similar but less nutritious formulations (1 and 5),
improved bioactivity. CONCLUSION: The results introduced two formulations of 1
and 5 as economically efficient liquid bioinoculants for Pseudomonas putida and
Pantoea agglomerans.
PMID- 28491249
TI - The seroprevalence of Mycoplasma pneumoniae IgM and IgG antibodies in patients
with ischemic stroke.
AB - BACKGROUND AND OBJECTIVES: Association between Mycoplasma pneumoniae infection
and increased risk for brain stroke has been well understood. Hence, the value of
serologic tests for assessing causative relationship between this infection and
brain stroke seems to be high. The present study aimed to determine serum level
of anti-Mycoplasma pneumoniae antibodies in patients with brain stroke and to
compare it with non-stroke patients. MATERIALS AND METHODS: This cross-sectional
study was performed on 97 consecutive ischemic stroke patients and 97 sex and age
matched non-stroke patients. Quantitative enzyme-linked immunosorbent assay
(ELISA) was established to measure the levels of anti-Mycoplasma pneumoniae IgG
and IgM antibodies. RESULTS: Regarding the level of anti-Mycoplasma pneumoniae
IgM, the titer of this marker was positive in 4.1% of patients with ischemic
stroke, while none of the subjects in control group had positive titer for this
antibody (OR = 1.043, 95%CI: 1.001 - 1.087, p = 0.043). The rate of positivity
for anti-Mycoplasma pneumoniae IgG in ischemic stroke patients was significantly
higher than in the control group (28.5% versus 13.4%, p = 0.031). Odds ratio for
exposure to M. pneumoniae was 2.24 times of the control subjects. The level of
anti-Mycoplasma pneumoniae IgM was independent to both sex and age variables in
patients group (p = 0.77). The level of anti-Mycoplasma pneumoniae IgG did not
depend on subjects' gender in control group, but was significantly higher in men
compared with women in patients group. CONCLUSION: A high level of anti
Mycoplasma pneumoniae IgM and IgG antibodies indicate a significant association
of M. pneumoniae infection and history of this infection with increased risk for
ischemic stroke.
PMID- 28491250
TI - Prevalence of Hepatitis C virus Genotype 3a in patients with Hodgkin and Non
Hodgkin Lymphoma.
AB - BACKGROUND AND OBJECTIVES: Hepatitis C virus (HCV) is a major public health
problem worldwide. Replication and persistence of HCV genome have been described
in the liver tissue as well as B cells lymphocyte. Several investigations have
reported that long-term persistence of HCV in B cells may result in Hodgkin and
Non-Hodgkin lymphoma. This study was aimed to determine frequency of HCV RNA in
histological tissues obtained from patients suffered from Hodgkin and Non-Hodgkin
lymphoma. MATERIALS AND METHODS: 52 formalin-fixed paraffin-embedded tissue
blocks including 23 (44.3%) Hodgkin and 29 (55.7%) Non-Hodgkin samples were
collected and five micrometer sections were prepared. RNA was extracted and cDNA
was synthesized. Two consecutive Nested RT-PCR assays were carried out for
detection of HCV 5' UTR and core gene. RT-PCR products were sequenced and aligned
to construct HCV phylogenic tree to evaluate the homology of sequences in
comparison to the reference sequences retrieved from Genbank. RESULTS: Overall, 6
Non-Hodgkin (20.6%) and 3 Hodgkin lymphoma (13.04%) samples showed positive PCR
results for both 5' UTR and HCV core RNA via nested PCR (P<0.469). Sequencing
results revealed that all detected HCV RNA samples belonged to the genotype 3a.
CONCLUSION: Despite low prevalence of HCV infection in Iran, high frequency of
HCV RNA genotypes 3a (17.3%) has been found in patients with Hodgkin and Non
Hodgkin lymphoma. To improve treatment regimens, screening of HCV RNA in patients
suffered from Hodgkin or Non-Hodgkin lymphoma is recommended which can be done
through highly sensitive molecular means before and after immunosuppression
status.
PMID- 28491251
TI - Significance of IgG optical density ratios (index value) in single reactive anti
Dengue virus IgG capture ELISA.
AB - BACKGROUND AND OBJECTIVES: A single reactive IgG anti-Dengue virus ELISA test in
the absence of IgM antibodies or NS1 antigen may denote current infection or past
exposure to the virus. To determine whether IgG index value can be used to
identify true current dengue infection we conducted a prospective observational
study. MATERIALS AND METHODS: Suspected dengue patients (n =1745) were tested in
their first specimen by MAC-ELISA, GAC-ELISA and NS1 antigen ELISA. Patients with
MAC-ELISA and NS1Antigen non-reactive but GAC-ELISA reactive results (n =57) in
their first test were followed up and repeated sampling was asked for IgG index
values were calculated according to the manufacturer's instruction and classified
as: low (2.2-2.5), medium (2.5-4.0) and high (>4.0). RESULTS: 16 out of 57
patients (28.1%) had low IgG Index value whereas 26 cases (45.6%) were
categorized as medium and 15(26.3%) were classified as patients with high IgG
index. Nine patients with paired reactive serology or antigen positive status
were categorised as serologically confirmed dengue fever, 11 patients as not
dengue with categorical evidence of other infections while the rest 37 casas with
clinical, radiological and laboratory parameters suggestive of dengue but no
serological confirmation as possible dengue. Among confirmed, possible and non
Dengue cases, 33.3, 32.4 and 0.0% had high Index value in comparison with 22.2,
29.7 and 27.3% showing low Index values, respectively. CONCLUSION: Our results
suggested a high IgG response in favour of true dengue infection than past
exposure while no conclusions should drawn from a low or medium reactive GAC
ELISA results in the absence of IgM antibodies and NS1 Ag.
PMID- 28491252
TI - Inhibitory effects of carvacrol on the expression of secreted aspartyl
proteinases 1-3 in fluconazole-resistant Candida albicans isolates.
AB - BACKGROUND AND OBJECTIVES: Secreted Aspartyl Proteinase (SAP) is one of the main
virulence factors in the pathogenesis of Candida. This enzyme is encoded by a
family of at least ten genes. Among these genes, the role of SAP1-3 in mucosal
infections is evident. This study aimed to investigate the expression of SAP1-3
genes of Candida albicans isolates after treatment with Echinophora platyloba
extract, carvacrol and caspofungin drug. MATERIALS AND METHODS: Vaginal samples
of 68 women with suspected vaginitis were obtained and cultured. Canida albicans
species were identified using phenotypic and genotyping methods.
Spectrophotometry was used to investigate the presence of SAP protein in the
vaginal samples, and SDS-PAGE was used to confirm its protein composition. Real
time PCR was performed to ascertain the effects of subinhibitory concentrations
of Echinophora platyloba extract, carvacrol and caspofungin on the expression of
SAP1-3 genes before and after treatment. RESULTS: C. albicans was found as the
abundant species (59.6%), and different amounts of SAP were present in all
vaginal samples, which were higher than Candida krusei strain. The protein
composition of SAP in C. albicans samples was estimated with the approximate
molecular weight of 45 kDa. mRNA levels of total SAP in FLU-resistant isolates
(P=0.01) were more than those of FLU-susceptible isolates (P=0.07). The findings
indicated that carvacrol is effective in reduction of SAP1-3 expression with a
particular effect against FLU-resistant isolates. CONCLUSION: Carvacrol contains
an essential oil (carvacrol); therefore, it can be considered as an alternative
effective antifungal compound.
PMID- 28491254
TI - Laser Science and its Applications in Prosthetic Rehabilitation.
AB - The minimal invasive nature of lasers, with quick tissue response and healing has
made them a very attractive technology in various fields of dentistry which
serves as a tool to create a better result than ever before. The rapid
development of lasers and their wavelengths with variety of applications on soft
and hard tissues may continue to have major impact on the scope and practice in
prosthetic dentistry. The purpose of this article is to make every clinician
familiar with the fundamentals of lasers and different laser systems to
incorporate into their clinical practices.
PMID- 28491253
TI - Isolation, molecular identification, and antifungal susceptibility profiles of
vaginal isolates of Candida species.
AB - BACKGROUND AND OBJECTIVES: Vulvovaginal candidiasis is a common fungal infection
among women during reproductive ages. Although, Candida albicans is accounted as
the main etiologic agent of vaginitis, non-albicans species have arisen during
last years. Resistant to antifungal drugs especially, fluconazole has been more
reported by researchers from around the World. The aims of this study were to
determine the prevalence of vulvovaginal candidiasis among suspected patients
with vaginitis, the frequency of Candida species, and the susceptibility profiles
of isolates to caspofungin, fluconazole and clotrimazole. MATERIALS AND METHODS:
One hundred and twenty suspected women with vaginitis were examined by specialist
physician and sampled using moisture swabs. Swabs were inoculated on CHROMagar
Candida plates, incubated at 35 degrees C and detected all isolated Candida
species using morphological, microcopy and molecular methods. The antifungal
susceptibility tests with caspofungin, fluconazole and clotrimazole were applied
using microdilution and Resazurin dye methods against all isolated yeasts.
RESULTS: The cultures were positive for 34(28.3%) samples and three Candida
species including; C. albicans (88.2%), C. glabrata (8.8%) and C. kefyr (2.9%).
Our study shows that only one isolate of C. albicans was resistant to caspofungin
at the concentration of 2 MUg/ml after 24h incubation that increased to 2
isolates after 48h incubation. All isolates were sensitive to fluconazole at the
MIC ranges of 1-0.25 MUg/ml, while 88.2% of them were inhibited at 0.25 MUg/mL of
clotrimazole. Candida albicans remains the most common agent of fungal vaginitis.
CONCLUSION: Although all of Candida isolates were susceptible to fluconazole in
vitro, it should be used with caution for empirical therapy due to more resistant
rates in clinic. In addition, due to valuable sensitivity of all tested strains
to caspofungin, it potentially can be presented as the first line therapy for
Candida vaginitis.
PMID- 28491255
TI - The Effect of Femtosecond Laser Treatment on the Effectiveness of Resin-Zirconia
Adhesive: An In Vitro Study.
AB - Introduction: When aesthetics is compromised, dental ceramics are excellent
materials for dental restorations; owing to their optical properties and
biocompatibility, zirconia ceramics are particularly interesting. Self-adhesive
resin cements are the most suitable for bonding to zirconia ceramics, but
traditional adhesive chemistry is ineffective and surface treatments are required
to improve the adhesive bonding between resin and zirconia. The aim of this study
was to evaluate the effect of femtosecond laser treatment on the shear bond
strength (SBS) of self-adhesive resin cement on zirconia surfaces and to contrast
it with other different surface conditioning methods. Methods: Sixty square
shaped zirconia samples were divided randomly into four groups (n = 15) according
to their surface conditioning method: the NT group - no surface treatment; the
APA25 group - airborne abrasion with 25 MUm alumina particles; the TSC group -
tribochemical silica coating, and the FS group - femtosecond laser irradiation
(800 nm, 4 mJ, 40 fs/pulse, 1 kHz). Self-adhesive resin cements were bonded at
the centre of samples, and after 72 hours, they were tested for SBS with a
universal testing machine at a crosshead speed of 0.5 mm/min, until fracture.
Five zirconia surfaces for each group were subjected to a surface morphology
analysis by scanning electron microscopy (SEM). The failure modes were noted and
a third of the specimens were prepared to morphological analysis. Results: The NT
group showed lower SBS values than the other groups. Femtosecond laser treatment
demonstrated higher values than the control and APA25 groups and similar values
to those of the TSC group. In the APA25 group, the surface conditioning method
had values close to those of the TSC group, but lower than those obtained with
femtosecond laser treatment. Conclusion: The treatment of zirconia with
femtosecond laser irradiation created a consistent and profound surface
roughness, improving the adhesive effectiveness of the zirconia-resin interface.
PMID- 28491256
TI - Effect of Antimicrobial Photodynamic Therapy as an Adjunct to Nonsurgical
Treatment of Deep Periodontal Pockets: A Clinical Study.
AB - Introduction: Deep periodontal pockets pose a great challenge for nonsurgical
periodontal treatment. Scaling and root planing (SRP) alone may not suffice in
cases where surgical therapy cannot be undertaken. Various recent studies have
suggested the use of antimicrobial Photodynamic Therapy (aPDT) for the management
of periodontal infections. The aim of this study was to evaluate the effects of
using aPDT along with SRP, compared to SRP alone for the management of deep
periodontal pockets. Methods: Thirty patients with chronic periodontitis, who met
the criteria of having periodontal pockets with depth >= 6 mm and bleeding on
probing (BOP) in at least 2 different quadrants were included. After SRP, one
quadrant was randomly selected for aPDT (test), while another served as control.
Clinical parameters i.e. plaque index (PI), modified sulcular bleeding index
(mSBI), probing depth (PD) and clinical attachment level (CAL) were measured at
baseline, 1 month and 3 months post-treatment intervals. Results: All clinical
parameters significantly improved in both groups after 1 and 3 months. At 1-month
interval, inter-group difference in mean change was statistically significant (P
< 0.05) in terms of mSBI (0.85 +/- 0.41in test vs 0.54 +/- 0.47 in control group)
and PD (1.77+/-0.86 in test vs 1.3 +/- 0.95 in control group). At 3 months
interval, no statistically significant difference was observed between test and
control groups except in terms of mSBI (0.97 +/- 0.45 in test vs 0.73 +/- 0.42 in
control group). Conclusion: aPDT appears to play an additional role in reduction
of gingival inflammation when used along with nonsurgical mechanical debridement
of deep periodontal pockets.
PMID- 28491257
TI - A Split Mouth Randomized Clinical Comparative Study to Evaluate the Efficacy of
Gingival Depigmentation Procedure Using Conventional Scalpel Technique or Diode
Laser.
AB - Introduction: Dark or black coloured gingiva is an esthetic concern especially in
subjects with high lip line or gummy smile. Gingival depigmentation procedure is
a type of perioplastic surgery where the gingival epithelium is excised with
various techniques to lighten the colour of the gingiva. The aim of this study
was to compare the clinical efficacy of gingival depigmentation procedure with
conventional scalpel technique and diode laser application. Methods: This split
mouth randomized study was conducted on 12 subjects (18-40 years of age),
exhibiting melanin hyperpigmentation of gingiva. The anterior labial sextant of
maxilla and mandible were divided into two halves involving three anterior teeth
i.e. central incisor, lateral incisor and canine on each side. The divided areas
were randomly allotted for depigmentation procedure either with scalpel technique
or diode laser operating at 980 nm wavelength. Various parameters such as
bleeding, pain, difficulty of procedure and wound healing were assessed and
compared between the two techniques. The level of melanin pigment was assessed
with Dummette Gupta index and photographic analysis with the help of adobe
software. The subjects were followed up to one year to see for recurrence of
melanin pigmentation. Results: Bleeding during surgery, pain score and difficulty
of procedure assessed by the operator were statistically higher for scalpel
technique as compared to laser technique. Wound healing did not show any
statistical significant difference between both techniques. Gingival
depigmentation procedures with scalpel as well as laser technique were effective
when compared preoperatively and at consecutive postoperative visits, and this
was statistically significant. Comparison of melanin depigmentation procedure
between scalpel and laser technique did not show any significant differences at
all postoperative intervals. Conclusion: The findings of the present study
suggest that gingival depigmentation was effective with both scalpel and laser
techniques. However, the laser treated sites showed reduced pain experienced by
the patient and better operator comfort. Slight melanin repigmentation was
observed in three subjects treated with scalpel depigmentation procedure at the
end of one year.
PMID- 28491258
TI - The Effect of Probe Pressure on In Vivo Single Fiber Reflectance Spectroscopy.
AB - Introduction: Single fiber reflectance spectroscopy (SFRS) is a noninvasive
procedure to quantitate tissue absorption and scattering properties. It can be
used to diagnose different diseases such as malignancy and pre-cancerous
conditions. The measurement is done with a fiber optic probe in contact with the
tissue surface. Herein, the effect of probe pressure on the extracted parameters
from human lip spectra was studied. Methods: Thirty-three normal subjects were
examined with three exerted pressure levels on the right, middle and left parts
of their lips. Results: The results showed variation of spectroscopic parameters
with different pressure levels. However, the effect was seen between a very mild
contact (pressure 1) and the other reasonably practical pressure levels normally
used in the medical centers. Conclusion: SFRS can be used as a reliable
diagnostic tool in clinics.
PMID- 28491259
TI - The Antibacterial Effect of Additional Photodynamic Therapy in Failed
Endodontically Treated Teeth: A Pilot Study.
AB - Introduction: Root canal therapy as a routine dental procedure has resulted in
retention of millions of teeth that would otherwise be lost. Unfortunately,
successful outcomes are not always achievable within initial endodontic
treatments, and that necessitates further treatment. Nonsurgical retreatment is
the first choice in most clinical situations. The aim of this clinical pilot
study was to assess the effect of additional photodynamic therapy (PDT) on
intraradicular bacterial load following retreatment of failed previously root
treated teeth. Methods: Thirty single-rooted/canalled endodontically treated
matured teeth (in 27 healthy patients) accompanied by apical periodontitis (AP)
were selected for this study. Standard protocol was followed for nonsurgical
retreatment of each tooth. Microbiological samples were taken after establishment
of apical patency, finished cleaning/shaping procedure, and PDT (665 nm, 1 W, 240
seconds). All samples were cultured for 72 hours and colony-forming unit (CFU)
was counted. McNemar test was used for statistical analysis of the data. The
level of significance was set at 0.001. Results: Routine cleaning and shaping
resulted in twenty four negative (80%) out of 30 cultures. Four additional
negative results were obtained after additional PDT (93.3%). The addition of PDT
to routine procedures significantly enhanced the number of bacteria-free samples
(P < 0.001). Conclusion: Regarding elimination of intraradicular microbiota,
additional PDT may increase the effectiveness of conventional chemomechanical
preparation in previously root filled teeth accompanied by AP. Well controlled
randomized clinical trials should be planned for future.
PMID- 28491260
TI - Evaluation of the Effects of Er,Cr:YSGG Laser, Ultrasonic Scaler and Curette on
Root Surface Profile Using Surface Analyser and Scanning Electron Microscope: An
In Vitro Study.
AB - Introduction: The periodontal therapy is primarily targeted at removal of dental
plaque and plaque retentive factors. Although the thorough removal of adherent
plaque, calculus and infected root cementum is desirable, it is not always
achieved by conventional modalities. To accomplish more efficient results several
alternative devices have been used. Lasers are one of the most promising
modalities for nonsurgical periodontal treatment as they can achieve excellent
tissue ablation with strong bactericidal and detoxification effects. Methods:
Thirty freshly extracted premolars were selected and decoronated. The mesial
surface of each root was divided vertically into four approximately equal parts.
These were distributed into four group based on the root surface treatment. Part
A (n = 30) was taken as control and no instrumentation was performed. Part B (n =
30) was irradiated by Erbium, Chromium doped Yttrium Scandium Gallium Garnet
(Er,Cr:YSGG) laser. Part C (n = 30) was treated by piezoelectric ultrasonic
scaler. Part D (n = 30) was treated by Gracey curette. The surface roughness was
quantitatively analyzed by profilometer using roughness average (Ra) value, while
presence of smear layer, cracks, craters and melting of surface were analyzed
using scanning electron microscope (SEM). The means across the groups were
statistically compared with control using Dunnett test. Results: Among the test
groups, Er,Cr:YSGG laser group showed maximum surface roughness (mean Ra value of
4.14 MUm) as compared to ultrasonic scaler (1.727 MUm) and curette group (1.22
MUm). However, surface with smear layer were found to be maximum (50%) in curette
treated samples and minimum (20%) in laser treated ones. Maximum cracks (83.34%)
were produced by ultrasonic scaler, and minimum (43.33%) by curettes. Crater
formation was maximum (50%) in laser treated samples and minimum (3.33%) in
curette treated ones. 63.33% samples treated by laser demonstrated melting of
root surface, followed by ultrasonic scaler and curettes. Conclusion: Er,Cr:YSGG
laser produced maximum microstructural changes on root surface that can influence
the attachment of soft periodontal tissues as well as plaque and calculus
deposition. In vivo studies are needed to validate these results and to evaluate
their clinical effects.
PMID- 28491261
TI - Effect of Combined Therapy Using Diode Laser and Photodynamic Therapy on Levels
of IL-17 in Gingival Crevicular Fluid in Patients With Chronic Periodontitis.
AB - Introduction: The aim of this study was to evaluate the efficacy of combination
therapy of diode laser and photodynamic therapy (PDT) as an adjunct to scaling
and root planing (SRP) on interleukin-17 (IL-17) levels in gingival crevicular
fluid (GCF) in patients with chronic periodontitis. Methods: Thirty subjects with
chronic periodontitis were included. All teeth received periodontal treatment
comprising of SRP. Using a split mouth study design, the test group was
additionally treated with a combination therapy of diode laser and PDT. GCF was
collected to evaluate IL-17 levels at baseline and 3 months. Results: There was
no difference in baseline values for levels of IL-17 in GCF in the test group and
the control group. A significant decrease in GCF levels of IL-17 was observed in
both treatment groups 3 months after treatment (P < 0.001). However, the
treatment groups showed no significant difference (P > 0.05). Conclusion: Based
on the results of the present study it was concluded that, GCF levels of IL-17
changed significantly after treatment regardless of treatment modality.
PMID- 28491262
TI - White Fibrous Papulosis of the Neck Treated With Fractionated 1550-nm Erbium
Glass Laser: A Case Report.
AB - Introduction: Despite its clinical features of multiple, confluent, small,
whitish, smooth, and clear-demarcate papules on the neck and back, the
pathogenesis of white fibrous papulosis of the neck (WFPN) is still unknown. The
lesions increase progressively and do not regress over time. However, no
effective treatment has yet been identified. Case Report: We reported the
successful results of a female patient receiving efficacious treatment for her
extensive lesions of WFPN with nonablative fractional photothermolysis laser
(Fractionated 1550-Erbium Glass laser). Conclusion: This photothermolysis laser
could then be suggestive as the therapeutic option for WFPN.
PMID- 28491263
TI - Periosteal Releasing Incision With Diode Laser in Guided Bone Regeneration
Procedure: A Case Series.
AB - Introduction: Periosteal releasing incision (PRI) is nearly always essential to
advance the flap sufficiently for a tension-free flap closure in bone
augmentation procedures. However, hematoma, swelling, and pain are recognized as
the main consequences of PRI with scalpel. The aim of this case series was to
investigate the effectiveness of laser-assisted PRI in guided bone regeneration
(GBR) procedure. In addition, postoperative hematoma, swelling, and pain and
implant success were assessed. Methods: Seventeen patients needed GBR were
included in this study. Diode laser (940 nm, 2 W, pulse interval: 1 ms, pulse
length: 1 ms, contact mode, 400-MUm fiber tip) was used in a contact mode to cut
the periosteum to create a tension-free flap. Facial hematoma, swelling, pain,
and the number of consumed nonsteroidal anti-inflammatory drugs (NSAIDs) were
measured for the six postoperative days. Six months after implant loading,
implant success was evaluated. Results: Minimal bleeding was encountered during
the procedure. A tension-free primary closure of the flap was achieved in all
cases. The clinical healing of the surgical area was uneventful. None of the
patients experienced hematoma, ecchymosis, or intense swelling after surgery. The
mean value of maximum pain (visual analogue scale - VAS) was 20.59 +/- 12.10 mm
(mild pain). Patients did not need to use NSAID after four postoperative days.
All implants were successful and functional and none of them failed after 6
months of implant loading. Conclusion: This study revealed the effectiveness of
laser-assisted PRI in GBR procedure. This technique was accompanied with minimal
sequelae at the first postoperative week. All implants were successful and no
complication was noted during the course of this study.
PMID- 28491264
TI - Priming radioimmunotherapy with external beam radiation in patients with relapsed
low grade non-Hodgkin lymphoma.
AB - BACKGROUND: The aim of this study was to evaluate the outcomes of priming salvage
radioimmunotherapy (RIT) with a low dose of external beam radiotherapy (EBRT) in
patients with relapsed low grade non-Hodgkin lymphoma (LG-NHL). METHODS: Patients
who received salvage RIT with or without 2 * 2 Gy EBRT between March 2009 and
February 2013 were retrospectively reviewed at a single institution. Planning
target volume (PTV) for EBRT was created by adding a 1-2 cm expansion to the
gross tumor volume depending on the anatomical location. Kaplan-Meier method via
log-rank was employed to analyze the endpoints freedom from progression (FFP) and
overall survival (OS). RESULTS: We identified 22 patients who received salvage
RIT without chemotherapy with a median follow up of 34 months. Of these, 9 (41%)
patients were treated with EBRT immediately prior to RIT, and 13 (59%) received
salvage RIT alone. Median FFP was not reached in patients who underwent
combination treatment, while it was 9 months for patients treated with RIT alone
(p = 0.02). OS for all patients at 36 months was 80.3% with no significant
difference between the two groups (p = 0.88). On univariate analysis, the
addition of EBRT was associated with improved FFP [hazard ratio (HR) = 4.17; 95%
confidence interval (CI), 1.24-19.1; p = 0.02)]. No long term toxicities were
reported in both groups. CONCLUSIONS: RIT outcomes and effects were improved with
addition of low-dose EBRT immediately prior to it, in the treatment of relapsed
LG-NHL with no additional toxicity. This study is hypothesis-generating and the
findings should be validated in prospective studies.
PMID- 28491265
TI - Experience with ruxolitinib in the treatment of polycythaemia vera.
AB - Polycythaemia vera (PV) is a myeloproliferative neoplasm classically
characterized by an erythrocytosis and is associated with a high risk of
thromboembolic events, constitutional symptoms burden and risk of transformation
to myelofibrosis and acute myeloid leukaemia. Therapy is directed at the
haematocrit (HCT) to reduce the risk of thrombotic events and usually comprises
low-dose aspirin and phlebotomy to maintain HCT at >45%. Frequently in addition,
cytoreductive therapy is indicated in high-risk patients for normalizing
haematological parameters to mitigate the occurrence of thromboembolic events.
Unfortunately, there is no clear evidence that current therapies reduce the risk
of transformation to myelofibrosis and for some a risk of a therapy related
complication is unknown for example leukaemia due to hydroxycarbamide (HC). First
line therapy for treating PV remains HC or interferon, the latter most often in
younger patients, especially those of childbearing age. However, therapy related
intolerance or resistance is a common feature and results in limited treatment
options for such patients. The discovery of the JAK2 V617F mutation and
consequently targeted therapy with Janus kinase inhibitors, in particular
ruxolitinib, has extended the spectrum of agents that can be used as second or
third line in PV. The findings of the phase II trial RESPONSE and the preliminary
data from RESPONSE 2 trial have identified a role for ruxolitinib in PV patients
who are resistant or intolerant to HC. In this article, using clinical cases we
demonstrate our experience with ruxolitinib highlighting the clinical benefits
and limitations we encountered in clinical practice.
PMID- 28491266
TI - Point-of-care ultrasonography (POCUS) in hemophilia A: a commentary on current
status and its potential role for improving prophylaxis management in severe
hemophilia A.
AB - In patients with severe hemophilia A, recurrent bleeding into joints results in
increased morbidity and reduced quality of life. Prophylaxis using replacement
factor products, especially when initiated early, has established benefits in
terms of reducing joint bleeds and preserving joint function. Poor adherence to
prophylactic regimens is a common cause for breakthrough bleeds and resultant
arthropathy. Improving prophylaxis management, especially in the transitional age
group, is a challenge. Here, we discuss the current status of ultrasonography
(US) in hemophilia A, challenges in its wider implementation, and the potential
for use of point-of-care US (POCUS) as an adjunct in the routine management of
patients with hemophilia following prophylaxis regimens. Using POCUS, in which US
is performed by trained hematologists and nonphysician operators (rather than
comprehensive US performed by imaging specialists), specific clinical questions
can be addressed in a time-efficient, user-friendly manner to promote adherence
to prophylaxis and guide or modify treatment approaches. This review also
discusses barriers to acceptance of POCUS as a part of routine management of
patients with hemophilia, including questions related to its diagnostic accuracy,
dependence on trained operators, agreement on appropriate scoring systems, and
potential usefulness in patient management.
PMID- 28491267
TI - Update on the management of giant cell arteritis.
AB - Giant cell arteritis (GCA) is a large vessel vasculitis that may be associated
with significant complications such as blindness, stroke, or aortic aneurysm and
dissection in a subset of patients. Given the serious side effects associated
with prolonged courses of glucocorticoids and frequent relapses experienced when
doses are tapered, increased efforts are being dedicated to the discovery of
safer and more effective therapies to control this disease. The purpose of this
review is to critically evaluate the role of glucocorticoid-sparing agents in the
medical management of GCA with a special focus on the most recent evidence
regarding the role of biologic agents, including tocilizumab (TCZ), abatacept and
ustekinumab, and other novel therapies.
PMID- 28491268
TI - Umeclidinium in chronic obstructive pulmonary disease: latest evidence and place
in therapy.
AB - Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity,
mortality and health care expenditure throughout the world. COPD guidelines
recommend the use of long-acting muscarinic antagonist (LAMA) either alone or in
combination with a long-acting beta2 agonist (LABA). For over 10 years,
tiotropium was the only LAMA that was used in the management of COPD. Over the
past few years, various new drugs have been identified that act on the muscarinic
receptors and beta2 receptors. Umeclidinium (Umec) is a new LAMA currently
approved for use in patients with COPD either as monotherapy or in combination
with vilanterol (Vil). Both Umec alone and in combination with Vil delivered
through a multi-dose dry powder ElliptaTM device have shown improvement in lung
function, health-related quality of life and exacerbation frequency in patients
with COPD. This review provides an overview of the pharmacology, pharmacodynamics
and pharmacokinetics of Umec, and evaluates the clinical efficacy and safety
studies in patients with COPD.
PMID- 28491269
TI - Curve Appeal: Exploring Individual Differences in Preference for Curved Versus
Angular Objects.
AB - A preference for smooth curvature, as opposed to angularity, is a well
established finding for lines, two-dimensional shapes, and complex objects, but
little is known about individual differences. We used two-dimensional black-and
white shapes-randomly generated irregular polygons, and arrays of circles and
hexagons-and measured many individual differences, including artistic expertise,
personality, and cognitive style. As expected, people preferred curved over
angular stimuli, and people's degree of curvature preference correlated across
the two sets of shapes. Multilevel models showed varying patterns of interaction
between shape and individual differences. For the irregular polygons, people
higher in artistic expertise or openness to experience showed a greater
preference for curvature. This pattern was not evident for the arrays of circles
and hexagons. We discuss the results in relation to the nature of the stimuli,
and we conclude that individual differences do play a role in moderating the
preference for smooth curvature.
PMID- 28491270
TI - Ways of Viewing Pictorial Plasticity.
AB - The plastic effect is historically used to denote various forms of stereopsis.
The vivid impression of depth often associated with binocular stereopsis can also
be achieved in other ways, for example, using a synopter. Accounts of this go
back over a hundred years. These ways of viewing all aim to diminish sensorial
evidence that the picture is physically flat. Although various viewing modes have
been proposed in the literature, their effects have never been compared. In the
current study, we compared three viewing modes: monocular blur, synoptic viewing,
and free viewing (using a placebo synopter). By designing a physical embodiment
that was indistinguishable for the three experimental conditions, we kept
observers naive with respect to the differences between them; 197 observers
participated in an experiment where the three viewing modes were compared by
performing a rating task. Results indicate that synoptic viewing causes the
largest plastic effect. Monocular blur scores lower than synoptic viewing but is
still rated significantly higher than the baseline conditions. The results
strengthen the idea that synoptic viewing is not due to a placebo effect.
Furthermore, monocular blur has been verified for the first time as a way of
experiencing the plastic effect, although the effect is smaller than synoptic
viewing. We discuss the results with respect to the theoretical basis for the
plastic effect. We show that current theories are not described with sufficient
details to explain the differences we found.
PMID- 28491271
TI - Stereoscopic Segmentation Cues Improve Visual Timing Performance in
Spatiotemporally Cluttered Environments.
AB - Recently, Cass and Van der Burg demonstrated that temporal order judgment (TOJ)
precision could be profoundly impaired by the mere presence of dynamic visual
clutter elsewhere in the visual field. This study examines whether presenting
target and distractor objects in different depth planes might ameliorate this
remote temporal camouflage (RTC) effect. TOJ thresholds were measured under
static and dynamic (flickering) distractor conditions. In Experiment 1, targets
were presented at zero, crossed, or uncrossed disparity, with distractors fixed
at zero disparity. Thresholds were significantly elevated under dynamic compared
with static contextual conditions, replicating the RTC effect. Crossed but not
uncrossed disparity targets improved performance in dynamic distractor contexts,
which otherwise produce substantial RTC. In Experiment 2, the assignment of
disparity was reversed: targets fixed at zero disparity; distractors crossed,
uncrossed, or zero. Under these conditions, thresholds improved significantly in
the nonzero distractor disparity conditions. These results indicate that
presenting target and distractor objects in different planes can significantly
improve TOJ performance in dynamic conditions. In Experiment 3, targets were each
presented with a different sign of disparity (e.g., one crossed and the other
uncrossed), with no resulting performance benefits. Results suggest that
disparity can be used to alleviate the performance-diminishing effects of RTC,
but only if both targets constitute a single and unique disparity-defined
surface.
PMID- 28491272
TI - Sensitivity to Nonaccidental Configurations of Two-Line Stimuli.
AB - According to Recognition-By-Components theory, object recognition relies on a
specific subset of three-dimensional shapes called geons. In particular, these
configurations constitute a powerful cue to three-dimensional object
reconstruction because their two-dimensional projection remains viewpoint
invariant. While a large body of literature has demonstrated sensitivity to
changes in these so-called nonaccidental configurations, it remains unclear what
information is used in establishing such sensitivity. In this study, we explored
the possibility that nonaccidental configurations can already be inferred from
the basic constituents of objects, namely, their edges. We constructed a set of
stimuli composed of two lines corresponding to various nonaccidental properties
and configurations underlying the distinction between geons, including
collinearity, alignment, curvature of contours, curvature of configuration axis,
expansion, cotermination, and junction type. Using a simple visual search
paradigm, we demonstrated that participants were faster at detecting targets that
differed from distractors in a nonaccidental property than in a metric property.
We also found that only some but not all of the observed sensitivity could have
resulted from simple low-level properties of our stimuli. Given that such
sensitivity emerged from a configuration of only two lines, our results support
the view that nonaccidental configurations could be encoded throughout the visual
processing hierarchy even in the absence of object context.
PMID- 28491273
TI - Estimating the Illumination Direction From Three-Dimensional Texture of Brownian
Surfaces.
AB - We studied whether human observers can estimate the illumination direction from
3D textures of random Brownian surfaces, containing undulations over a range of
scales. The locally Lambertian surfaces were illuminated with a collimated beam
from random directions. The surfaces had a uniform albedo and thus texture
appeared only through shading and shadowing. The data confirm earlier results
with Gaussian surfaces, containing undulations of a single scale. Observers were
able to accurately estimate the source azimuth. If shading dominated the images,
the observers committed 180 degrees errors. If cast shadows were present, they
resolved this convex-concave-ambiguity almost completely. Thus, observers relied
on second-order statistics in the shading regime and used an unidentified first
order cue in the shadow regime. The source elevations could also be estimated,
which can be explained by the observers' exploitation of the statistical
homogeneity of the stimulus set. The fraction of the surface that is in shadow
and the median intensity are likely cues for these elevation estimates.
PMID- 28491275
TI - Outflow tract septation and the aortic arch system in reptiles: lessons for
understanding the mammalian heart.
AB - BACKGROUND: Cardiac outflow tract patterning and cell contribution are studied
using an evo-devo approach to reveal insight into the development of aorto
pulmonary septation. RESULTS: We studied embryonic stages of reptile hearts
(lizard, turtle and crocodile) and compared these to avian and mammalian
development. Immunohistochemistry allowed us to indicate where the essential cell
components in the outflow tract and aortic sac were deployed, more specifically
endocardial, neural crest and second heart field cells. The neural crest-derived
aorto-pulmonary septum separates the pulmonary trunk from both aortae in
reptiles, presenting with a left visceral and a right systemic aorta arising from
the unseptated ventricle. Second heart field-derived cells function as flow
dividers between both aortae and between the two pulmonary arteries. In birds,
the left visceral aorta disappears early in development, while the right systemic
aorta persists. This leads to a fusion of the aorto-pulmonary septum and the
aortic flow divider (second heart field population) forming an avian aorto
pulmonary septal complex. In mammals, there is also a second heart field-derived
aortic flow divider, albeit at a more distal site, while the aorto-pulmonary
septum separates the aortic trunk from the pulmonary trunk. As in birds there is
fusion with second heart field-derived cells albeit from the pulmonary flow
divider as the right 6th pharyngeal arch artery disappears, resulting in a
mammalian aorto-pulmonary septal complex. In crocodiles, birds and mammals, the
main septal and parietal endocardial cushions receive neural crest cells that are
functional in fusion and myocardialization of the outflow tract septum. Longer
lasting septation in crocodiles demonstrates a heterochrony in development. In
other reptiles with no indication of incursion of neural crest cells, there is
either no myocardialized outflow tract septum (lizard) or it is vestigial
(turtle). Crocodiles are unique in bearing a central shunt, the foramen of
Panizza, between the roots of both aortae. Finally, the soft-shell turtle
investigated here exhibits a spongy histology of the developing carotid arteries
supposedly related to regulation of blood flow during pharyngeal excretion in
this species. CONCLUSIONS: This is the first time that is shown that an interplay
of second heart field-derived flow dividers with a neural crest-derived cell
population is a variable but common, denominator across all species studied for
vascular patterning and outflow tract septation. The observed differences in
normal development of reptiles may have impact on the understanding of
development of human congenital outflow tract malformations.
PMID- 28491274
TI - Biomimetic strategies for fracture repair: Engineering the cell microenvironment
for directed tissue formation.
AB - Complications resulting from impaired fracture healing have major clinical
implications on fracture management strategies. Novel concepts taken from
developmental biology have driven research strategies towards the elaboration of
regenerative approaches that can truly harness the complex cellular events
involved in tissue formation and repair. Advances in polymer technology and a
better understanding of naturally derived scaffolds have given rise to novel
biomaterials with an increasing ability to recapitulate native tissue
environments. This coupled with advances in the understanding of stem cell
biology and technology has opened new avenues for regenerative strategies with
true clinical translatability. These advances have provided the impetus to
develop alternative approaches to enhance the fracture repair process. We provide
an update on these advances, with a focus on the development of novel biomimetic
approaches for bone regeneration and their translational potential.
PMID- 28491276
TI - Antiangiogenic effects in patients with progressive desmoplastic small round cell
tumor: data from the French national registry dedicated to the use of off-labeled
targeted therapy in sarcoma (OUTC's).
AB - BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a very rare
mesenchymal tumor that mainly affects teenagers and young adults with a mean age
at diagnosis around 20-25 years. Although initial management still needs
standardization, many centers will use multimodal treatment including intensive
chemotherapy, extensive surgical resection followed by radiotherapy. Despite
this, prognosis remains very poor and the median overall survival is 25 months.
Recurrent disease is mainly treated by chemotherapy. Recently, due to the unmet
medical need for recurrent disease, targeted therapies were explored for DSRCT.
METHODS: In this study, we assessed the response rate and progression free
survival in nine cases of progressive DSRCT included in the OUTC's registry and
treated with antiangiogenics targeted agents (sunitinib, sorafenib and
bevacizumab). OUTC's, a French national registry, collects data about the use of
off-label targeted therapy in sarcoma. RESULTS: Eight males and one woman were
included, with median age at diagnosis of 27.3 years (range from 9 to 48 years).
They received a mean 3 lines (2-5) of treatment before antiangiogenic agent
initiation. Six patients received sunitinib, two received sorafenib and one
bevacizumab. Median progression free survival was 3.1 months (range 2-5.5 months)
and best response observed was 5.5 months stable disease. Most patients had
manageable low-grade toxicities, mainly fatigue, abdominal pain and skin
toxicity. CONCLUSIONS: Despite very limited activity of antiangiogenics in our
study, prospective collection of cases of these rare tumors together with
molecular data should guide therapeutic decision and enhance outcome.
PMID- 28491277
TI - Meta-analysis of crowdsourced data compendia suggests pan-disease transcriptional
signatures of autoimmunity.
AB - Background: The proliferation of publicly accessible large-scale biological data
together with increasing availability of bioinformatics tools have the potential
to transform biomedical research. Here we report a crowdsourcing Jamboree that
explored whether a team of volunteer biologists without formal bioinformatics
training could use OMiCC, a crowdsourcing web platform that facilitates the reuse
and (meta-) analysis of public gene expression data, to compile and annotate gene
expression data, and design comparisons between disease and control sample
groups. Methods: The Jamboree focused on several common human autoimmune
diseases, including systemic lupus erythematosus (SLE), multiple sclerosis (MS),
type I diabetes (DM1), and rheumatoid arthritis (RA), and the corresponding mouse
models. Meta-analyses were performed in OMiCC using comparisons constructed by
the participants to identify 1) gene expression signatures for each disease
(disease versus healthy controls at the gene expression and biological pathway
levels), 2) conserved signatures across all diseases within each species (pan
disease signatures), and 3) conserved signatures between species for each disease
and across all diseases (cross-species signatures). Results: A large number of
differentially expressed genes were identified for each disease based on meta
analysis, with observed overlap among diseases both within and across species.
Gene set/pathway enrichment of upregulated genes suggested conserved signatures
(e.g., interferon) across all human and mouse conditions. Conclusions: Our
Jamboree exercise provides evidence that when enabled by appropriate tools, a
"crowd" of biologists can work together to accelerate the pace by which the
increasingly large amounts of public data can be reused and meta-analyzed for
generating and testing hypotheses. Our encouraging experience suggests that a
similar crowdsourcing approach can be used to explore other biological questions.
PMID- 28491278
TI - Recent advances in the management of acute ischemic stroke.
AB - In recent years, several landmark trials have transformed acute ischemic stroke
care. The most dramatic results from the field of acute endovascular intervention
demonstrate unequivocal benefit for a select group of patients with moderate to
severe deficits presenting within 7 hours from onset and with occlusions of
proximal arteries in the anterior circulation. In addition, technological
advances and workflow efficiencies have facilitated more rapid delivery of acute
stroke interventions. This review provides an overview of recent advances in the
management of acute ischemic stroke.
PMID- 28491279
TI - "Mesenchymal stem cells": fact or fiction, and implications in their therapeutic
use.
AB - The concept of a post-natal "mesenchymal stem cell" ("MSC") originated from
studies focused on bone marrow stromal cells (BMSCs), which are non-hematopoietic
adherent cells, a subset of which are skeletal stem cells (SSCs), able to form
cartilage, bone, hematopoiesis-supportive stroma, and marrow adipocytes based on
rigorous clonal and differentiation assays. Subsequently, it was speculated that
BMSCs could form other mesodermal derivatives and even cell types from other germ
layers. Based on BMSC surface markers, representative of fibroblastic cells, and
imprecise differentiation assays, it was further imagined that "MSCs" are
ubiquitous and equipotent. However, "MSCs" do not have a common embryonic origin
and are not a lineage, but recent studies indicate that they are tissue-specific
stem/progenitor cells. These cells share cell surface features owing to their
fibroblastic nature, but they are not identical. They display different
differentiation capacities based on their tissue origin but do not "trans
differentiate" outside of their lineage, based on rigorous assays. For these
reasons, the "MSC" term should be abandoned. Tissue-specific stem/progenitor
cells provide the opportunity to devise methods for tissue regeneration by the
cells themselves (tissue engineering). Their use in other forms of regenerative
medicine based on paracrine, immunosuppressive, and immunomodulatory effects is
far less clear.
PMID- 28491280
TI - AR2, a novel automatic artifact reduction software method for ictal EEG
interpretation: Validation and comparison of performance with commercially
available software.
AB - Objective: To develop a novel software method (AR2) for reducing muscle
contamination of ictal scalp electroencephalogram (EEG), and validate this method
on the basis of its performance in comparison to a commercially available
software method (AR1) to accurately depict seizure-onset location. Methods: A
blinded investigation used 23 EEG recordings of seizures from 8 patients. Each
recording was uninterpretable with digital filtering because of muscle artifact
and processed using AR1 and AR2 and reviewed by 26 EEG specialists. EEG readers
assessed seizure-onset time, lateralization, and region, and specified confidence
for each determination. The two methods were validated on the basis of the number
of readers able to render assignments, confidence, the intra-class correlation
(ICC), and agreement with other clinical findings. Results: Among the 23
seizures, two-thirds of the readers were able to delineate seizure-onset time in
10 of 23 using AR1, and 15 of 23 using AR2 (p<0.01). Fewer readers could
lateralize seizure-onset (p<0.05). The confidence measures of the assignments
were low (probable-unlikely), but increased using AR2 (p<0.05). The ICC for
identifying the time of seizure-onset was 0.15 (95% confidence interval (CI),
0.11-0.18) using AR1 and 0.26 (95% CI 0.21-0.30) using AR2. The EEG
interpretations were often consistent with behavioral, neurophysiological, and
neuro-radiological findings, with left sided assignments correct in 95.9% (CI
85.7-98.9%, n=4) of cases using AR2. Conclusions: EEG artifact reduction methods
for localizing seizure-onset does not result in high rates of interpretability,
reader confidence, and inter-reader agreement. However, the assignments by groups
of readers are often congruent with other clinical data. Utilization of the AR2
software method may improve the validity of ictal EEG artifact reduction.
PMID- 28491281
TI - Annotated mitochondrial genome with Nanopore R9 signal for Nippostrongylus
brasiliensis.
AB - Nippostrongylus brasiliensis, a nematode parasite of rodents, has a parasitic
life cycle that is an extremely useful model for the study of human hookworm
infection, particularly in regards to the induced immune response. The current
reference genome for this parasite is highly fragmented with minimal annotation,
but new advances in long-read sequencing suggest that a more complete and
annotated assembly should be an achievable goal. We de-novo assembled a single
contig mitochondrial genome from N. brasiliensis using MinION R9 nanopore data.
The assembly was error-corrected using existing Illumina HiSeq reads, and
annotated in full (i.e. gene boundary definitions without substantial gaps) by
comparing with annotated genomes from similar parasite relatives. The
mitochondrial genome has also been annotated with a preliminary electrical
consensus sequence, using raw signal data generated from a Nanopore R9 flow cell.
PMID- 28491282
TI - Cell growth inhibition and apoptotic effects of a specific anti-RTFscFv antibody
on prostate cancer, but not glioblastoma, cells.
AB - Background: Single chain antibody (scFv) has shown interesting results in cancer
immunotargeting approaches, due to its advantages over monoclonal antibodies.
Regeneration and tolerance factor (RTF) is one of the most important regulators
of extracellular and intracellular pH in eukaryotic cells. In this study, the
inhibitory effects of a specific anti-RTF scFv were investigated and compared
between three types of prostate cancer and two types of glioblastoma cells.
Methods: A phage antibody display library of scFv was used to select specific
scFvs against RTF using panning process. The reactivity of a selected scFv was
assessed by phage ELISA. The anti-proliferative and apoptotic effects of the
antibody on prostate cancer (PC-3, Du-145 and LNCaP) and glioblastoma (U-87 MG
and A-172) cell lines were investigated by MTT and Annexin V/PI assays. Results:
A specific scFv with frequency 35% was selected against RTF epitope. This
significantly inhibited the proliferation of the prostate cells after 24 h. The
percentages of cell viability (using 1000 scFv/cell) were 52, 61 and 73% for PC
3, Du-145 and LNCaP cells, respectively, compared to untreated cells. The
antibody (1000 scFv/cell) induced apoptosis at 50, 40 and 25% in PC-3, Du-145 and
LNCaP cells, respectively. No growth inhibition and apoptotic induction was
detected for U-87 and A172 glioblastoma cells. Conclusions: Anti-RTFscFv
significantly reduced the proliferation of the prostate cancer cells. The
inhibition of cell growth and apoptotic induction effects in PC-3 cells were
greater than Du-145 and LNCaP cells. This might be due to higher expression of
RTF antigen in PC-3 cells and/or better accessibility of RTF to scFv antibody.
The resistance of glioblastoma cells to anti-RTF scFv offers the existence of
mechanism(s) that abrogate the inhibitory effect(s) of the antibody to RTF. The
results suggest that the selected anti-RTF scFv antibody could be an effective
new alternative for prostate cancer immunotherapy.
PMID- 28491283
TI - Open Online Courses in Public Health: experience from Peoples-uni.
AB - Open Online Courses (OOCs) are offered by Peoples-uni at http://ooc.peoples
uni.org to complement the courses run on a separate site for academic credit at
http://courses.peoples-uni.org. They provide a wide range of online learning
resources beyond those usually found in credit bearing Public Health courses.
They are self-paced, and students can enrol themselves at any time and utilise
Open Educational Resources free of copyright restrictions. In the two years that
courses have been running, 1174 students from 100 countries have registered and
among the 1597 enrollments in 15 courses, 15% gained a certificate of completion.
Easily accessible and appealing to a wide geographical and professional audience,
OOCs have the potential to play a part in establishing global Public Health
capacity building programmes.
PMID- 28491284
TI - Hermaphroditism in the white spot grouper Epinephelus coeruleopunctatus (Pisces:
Serranidae) harvested from Padang City waters, Indonesia.
AB - The objective of the present study was to determine the length (mm) for sex
transformation of hermaphroditism in white spot grouper Epinephelus
coeruleopunctatus as a basis for developing breeding technology. Fish sampling
was carried out between April and October 2013 in Padang City waters, Indonesia.
A total of 56 white spot groupers were recorded during the study; of these 22
were male, 28 female and 6 samples were not recognized regarding sex preference.
Sex differentiation was detected at a length of 183 mm, and at this size the fish
are female. Sex transformation to male begun to occur at 302 mm total length.
PMID- 28491285
TI - Midlife interventions are critical in prevention, delay, or improvement of
Alzheimer's disease and vascular cognitive impairment and dementia.
AB - The basic strategy for focusing exclusively on genetically identified targets for
intervening in late life dementias was formulated 30 years ago. Three decades
and billions of dollars later, all efforts at disease-modifying interventions
have failed. Over that same period, evidence has accrued pointing to dementias
as late-life clinical phenotypes that begin as midlife pathologies. Effective
prevention therefore may need to begin in midlife, in order to succeed. No
current interventions are sufficiently safe to justify their use in midlife
dementia prevention trials. Observational studies could be informative in
testing the proposal that amyloid imaging and APOEepsilon 4 genotype can predict
those who are highly likely to develop Alzheimer's disease and in whom higher
risk interventions might be justifiable. A naturally occurring, diet-responsive
cognitive decline syndrome occurs in canines that closely resembles human
Alzheimer's. Canine cognitive dysfunction could be useful in estimating how
early intervention must begin in order to succeed. This model may also help
identify and assess novel targets and strategies. New approaches to dementia
prevention are urgently required, since none of the world's economies can sustain
the costs of caring for this epidemic of brain failure that is devastating half
of the over 85-year-olds globally.
PMID- 28491286
TI - Unwinding focal segmental glomerulosclerosis.
AB - Focal segmental glomerulosclerosis (FSGS) represents the most common primary
glomerular disease responsible for the development of end-stage renal disease
(ESRD) in the United States (US). The disease progresses from podocyte injury to
chronic kidney disease (CKD), ultimately leading to total nephron degeneration.
Extensive basic science research has been conducted to unwind the mechanisms of
FSGS and, with those insights, understand major contributors of CKD in general.
As a result, several putative molecules and pathways have been studied, all
implicated in the disease; some serve, in addition, as early biomarkers. The
ongoing research is currently focusing on understanding how these molecules and
pathways can interplay and be utilized as potential diagnostic and therapeutic
targets. Among these molecules, the soluble urokinase plasminogen activating
receptor (suPAR) has been studied in detail, both clinically and from a basic
science perspective. By now, it has emerged as the earliest and most robust
marker of future CKD. Other circulating factors harming podocytes include anti
CD40 auto-antibody and possibly cardiotrophin-like cytokine factor-1.
Understanding these factors will aid our efforts to ultimately cure FSGS and
possibly treat a larger portion of CKD patients much more effectively.
PMID- 28491287
TI - Linking cortical microtubule attachment and exocytosis.
AB - Exocytosis is a fundamental cellular process whereby secreted molecules are
packaged into vesicles that move along cytoskeletal filaments and fuse with the
plasma membrane. To function optimally, cells are strongly dependent on precisely
controlled delivery of exocytotic cargo. In mammalian cells, microtubules serve
as major tracks for vesicle transport by motor proteins, and thus microtubule
organization is important for targeted delivery of secretory carriers. Over the
years, multiple microtubule-associated and cortical proteins have been discovered
that facilitate the interaction between the microtubule plus ends and the cell
cortex. In this review, we focus on mammalian protein complexes that have been
shown to participate in both cortical microtubule capture and exocytosis, thereby
regulating the spatial organization of secretion. These complexes include
microtubule plus-end tracking proteins, scaffolding factors, actin-binding
proteins, and components of vesicle docking machinery, which together allow
efficient coordination of cargo transport and release.
PMID- 28491290
TI - DNA nanochannels.
AB - Transmembrane proteins are mostly nanochannels playing a highly important role in
metabolism. Understanding their structures and functions is vital for revealing
life processes. It is of fundamental interest to develop chemical devices to
mimic biological channels. Structural DNA nanotechnology has been proven to be a
promising method for the preparation of fine DNA nanochannels as a result of the
excellent properties of DNA molecules. This review presents the development
history and current situation of three different types of DNA nanochannel: tile
based nanotube, DNA origami nanochannel, and DNA bundle nanochannel.
PMID- 28491288
TI - Selective vulnerabilities and biomarkers in neurocognitive aging.
AB - As the world's population continues to age, an understanding of the aging brain
becomes increasingly crucial. This review focuses on several recent ideas and
findings in the study of neurocognitive aging, specifically focusing on episodic
memory, and discusses how they can be considered and used to guide us moving
forward. Topics include dysfunction in neural circuits, the roles of neurogenesis
and inhibitory signaling, vulnerability in the entorhinal cortex, individual
differences, and comorbidities. These avenues of study provide a brief overview
of promising themes in the field and together provide a snapshot of what we
believe will be important emerging topics in selective vulnerabilities in the
aging brain.
PMID- 28491289
TI - Recent advances in preoperative management of esophageal adenocarcinoma.
AB - Esophageal cancer is an aggressive malignancy with increasing incidence, and the
prognosis of patients treated by surgery alone remains dismal. Preoperative
treatment can modestly prolong overall survival. Preoperative chemotherapy or
chemoradiation is the standard of care for resectable esophageal cancer (greater
than clinical stage I and less than clinical stage IV). One of the challenges is
to predict complete response in the surgical specimen from preoperative therapy
and to avoid surgery in some patients but also predict ineffectiveness of
preoperative therapy if the tumor is resistant and avoid such therapies
altogether. In-depth understanding of the molecular biology could lead to
personalized therapy, and in the future, clinical trials designed according to
molecular features are expected. Here, we summarize preoperative treatment for
esophageal adenocarcinoma and their potential.
PMID- 28491291
TI - Recent advances in the management and understanding of macular degeneration.
AB - Current management of age-related macular degeneration (AMD) is directed at
intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors
for the treatment of wet AMD and supplementation with oral antioxidants for the
treatment of dry AMD. In this article, we will review recent clinical trials for
the treatment of dry and wet AMD.
PMID- 28491293
TI - What's new in the management of adult bronchiectasis?
AB - Bronchiectasis is a heterogeneous, chronic condition with many aetiologies. It
poses a significant burden on patients and healthcare practitioners and services.
Clinical exacerbations often result in reduced quality of life, increased rate of
lung function decline, increased hospitalisation, and mortality. Recent focus in
respiratory research, guidelines, and future management options has improved this
clinical field in evidence-based practice, but further work and phase III
clinical trials are required. This article aims to summarise and explore advances
in management strategies in recent years and highlight areas of research and
future focus.
PMID- 28491294
TI - Prevalence and pattern of antibiotic resistance of Staphylococcus aureus isolated
from door handles and other points of contact in public hospitals in Ghana.
AB - BACKGROUND: Studies have implicated Staphylococcus aureus as the leading cause of
septicemia in the Tamale metropolis of Ghana. The aim of this study was to
determine the prevalence and antibiotic susceptibility of S. aureus and
Methicillin Resistant S. aureus (MRSA) in the environments of three hospitals in
Ghana. METHODS: A total of 120 swab samples were taken from door handles, stair
railings and other points of contact at Tamale Teaching Hospital, Tamale Central
Hospital and Tamale West Hospital. The swab samples were directly plated on
Mannitol Salt and Baird Parker agar plates and incubated at 37 degrees C (+/- 2)
for 18-24 h. An antibiotic susceptibility test was performed using the Clinical
Laboratory Standard Institute's guidelines. Isolates resistant to both cefoxitin
and oxacillin were considered to be MRSA. RESULTS: A total of 47 (39%) positive
S. aureus samples were isolated from all three hospitals, of which, eight (17%)
were putative MRSA isolates. One MRSA isolate was resistant to all the
antibiotics used (cefoxitin, oxacillin, ciprofloxacin, erythromycin,
tetracycline, ampicillin, streptomycin and sulfamethoxazole-trimethoprim). Five
of the MRSA isolates were multi-drug resistant, whilst the other three were
resistant to only two antibiotics. All the multi-drug resistant MRSA isolates
were resistant to at least four antibiotics. The percentage of isolates resistant
to oxacillin, ampicillin, ciprofloxacin, tetracycline, streptomycin,
erythromycin, and sulfamethoxazole/trimethoprim were 17, 13, 9, 28, 89, 13 and
11% respectively. CONCLUSION: The high multi-drug resistance of MRSA in hospital
environments in Ghana reinforces the need for the effective and routine cleaning
of door handles in hospitals. Further investigation is required to understand
whether S. aureus from door handles could be the possible causes of nosocomial
diseases in the hospitals.
PMID- 28491292
TI - Looking at the recent advances in understanding alpha-synuclein and its
aggregation through the proteoform prism.
AB - Despite attracting the close attention of multiple researchers for the past 25
years, alpha-synuclein continues to be an enigma, hiding sacred truth related to
its structure, function, and dysfunction, concealing mechanisms of its
pathological spread within the affected brain during disease progression, and,
above all, covering up the molecular mechanisms of its multipathogenicity, i.e.
the ability to be associated with the pathogenesis of various diseases. The goal
of this article is to present the most recent advances in understanding of this
protein and its aggregation and to show that the remarkable structural,
functional, and dysfunctional multifaceted nature of alpha-synuclein can be
understood using the proteoform concept.
PMID- 28491295
TI - Magnetic resonance imaging planning in children with complex congenital heart
disease - A new approach.
AB - OBJECTIVES: To compare a standard sequential 2D Planning Method (2D-PM) with a 3D
offline Planning Method (3D-PM) based on 3D contrast-enhanced magnetic resonance
angiography (CE-MRA) in children with congenital heart disease (CHD). DESIGN: In
14 children with complex CHD (mean: 2.6 years, range: 3 months to 7.6 years),
axial and coronal cuts were obtained with single slice spin echo sequences to get
the final double oblique longitudinal cut of the targeted anatomical structure
(2D-PM, n = 31). On a separate workstation, similar maximal intensity projection
(MIP) images were generated offline from a 3D CE-MRA. MIP images were localizers
for repeated targeted imaging using the previous spin echo sequence (3D-PM).
Finally, image coverage, spatial orientation and acquisition time were compared
for 2D-PM and 3D-PM. MAIN OUTCOME MEASURES: 2D-PM and 3D-PM images were similar:
both perfectly covered the selected anatomic regions and no spatial differences
were found (p>0.05). The mean time for creation of the final imaging plane was
241 +/- 31 s (2D-PM) compared to 71 +/- 18 s (3D-PM) (p<0.05). CONCLUSIONS: 3D-PM
shows similar results compared to 2D-PM, but allows faster and offline planning
thereby reducing the scan time significantly. As newly developed high-resolution
3D datasets can also be used further improvement of this technology is expected.
PMID- 28491296
TI - Assessment of the 10-year risk of cardiovascular disease among a group of
patients on maintenance hemodialysis: A cross-sectional study from Cameroon.
AB - OBJECTIVE: To assess the 10-year risk of cardiovascular disease and potential
impacting factors among patients undergoing hemodialysis in Yaounde, Cameroon.
DESIGN: A cross-sectional study in January 2016. SETTING: Patients were recruited
at the dialysis unit of the Yaounde University Teaching Hospital, Cameroon.
PARTICIPANTS: These were hemodialysis patients aged 20 years and above, dialyzing
in the above unit since at least 3 months and volunteering to be enrolled in the
study. MAIN OUTCOME MEASURES: The risk of cardiovascular disease was assessed
using the Framingham risk score. RESULTS: We included 44 patients. The risk of
cardiovascular disease ranged from less than 1% to more than 30% with a median of
12.3% (interquartile range 4.9-24.4). Twenty hemodialysis patients (45.5%) had a
low risk of cardiovascular disease (<10%), 10 (22.7%), a moderate risk (10-20%),
and 14 (31.8%) presented a high risk of cardiovascular disease (>20%). In
multivariable linear regression analysis, duration on dialysis (adjusted beta =
0.11; p = 0.003), number of weekly sessions of physical activity (adjusted beta =
-1.35; p = 0.018), fasting serum glucose levels (adjusted beta = 4.22; p =
0.022), serum triglycerides levels (adjusted beta = 5.94; p = 0.033), and serum
urea levels (adjusted beta = -2.08; p = 0.039) were independently impacting our
patients' risk of cardiovascular disease. CONCLUSION: Around 55% of our study
population presented a moderate or high risk of cardiovascular disease. Duration
on dialysis, number of physical activity sessions per week, fasting serum
glucose, serum triglycerides, and serum urea levels may impact our hemodialysis
patients' risk of cardiovascular disease.
PMID- 28491298
TI - Low back pain clinical guidelines: similarities and divergent views across the
pond.
PMID- 28491297
TI - Net energy of corn, soybean meal and rapeseed meal in growing pigs.
AB - BACKGROUND: Two experiments were conducted to estimate the net energy (NE) of
corn, soybean meal, expeller-pressed rapeseed meal (EP-RSM) and solvent-extracted
rapeseed meal (SE-RSM) using indirect calorimetry and to validate the NE of these
four ingredients using pig growth performance. METHODS: In Exp.1, 24 barrows
(initial BW = 36.4 +/- 1.6 kg) were allotted to 1 of 4 diets which included a
corn basal diet, a corn-soybean meal basal diet and two rapeseed meal diets
containing 20% EP-RSM (9.5% ether extract) or SE-RSM (1.1% ether extract)
substituted for corn and soybean meal. The design allowed the calculation of NE
values of corn, soybean meal and rapeseed meals according to the difference
method. In Exp.2, 175 growing pigs (initial BW = 36.0 +/- 5.2 kg) were fed 1 of 5
diets for 28 d, with five pigs per pen and seven replications (pens) per
treatment in order to validate the measured energy values. Diets were a corn
soybean meal diet and four diets including 10% or 20% EP-RSM and 10% or 20% SE
RSM. RESULTS: The NE of corn, soybean meal, EP-RSM and SE-RSM were 12.46, 11.34,
11.71 and 8.83 MJ/kg DM, respectively. The NE to ME ratio of corn (78%) was
similar to tabular values, however, the NE to ME ratios of soybean meal (70%) and
rapeseed meal (76%) were greater than tabular values. The greater NE value in EP
RSM than in SE-RSM is consistent with its higher EE content. Increasing EP-RSM or
SE-RSM did not affect the growth performance of pigs and the caloric efficiency
of NE was comparable for all diets. CONCLUSIONS: The NE of EP-RSM was similar to
soybean meal, and both were greater than SE-RSM. The DE, ME and NE values
measured in Exp.1 are confirmed by results of Exp. 2 with comparable caloric
efficiencies of DE, ME or NE for all diets.
PMID- 28491299
TI - Contextual modulation of pain sensitivity utilising virtual environments.
AB - BACKGROUND: Investigating psychological mechanisms that modulate pain, such as
those that might be accessed by manipulation of context, is of great interest to
researchers seeking to better understand and treat pain. The aim of this study
was to better understand the interaction between pain sensitivity, and contexts
with inherent emotional and social salience - by exploiting modern immersive
virtual reality (VR) technology. METHODS: A within-subjects, randomised, double
blinded, repeated measures (RM) design was used. In total, 25 healthy
participants were exposed to neutral, pleasant, threatening, socially positive
and socially negative contexts, using an Oculus Rift DK2. Pressure pain
thresholds (PPTs) were recorded in each context, as well as prior to and
following the procedure. We also investigated whether trait anxiety and pain
catastrophisation interacted with the relationship between the different contexts
and pain. RESULTS: Pressure pain sensitivity was not modulated by context (p =
0.48). Anxiety and pain catastrophisation were not significantly associated with
PPTs, nor did they interact with the relationship between context and PPTs.
CONCLUSION: Contrary to our hypothesis, socially and emotionally salient contexts
did not influence pain thresholds. In light of other research, we suggest that
pain outcomes might only be tenable to manipulation by contextual cues if they
specifically manipulate the meaning of the pain-eliciting stimulus, rather than
manipulate psychological state generally - as per the current study. Future
research might exploit immersive VR technology to better explore the link between
noxious stimuli and contexts that directly alter its threat value.
PMID- 28491300
TI - Schoolbags and back pain in children between 8 and 13 years: a national study.
AB - Schoolbag weight in schoolchildren is a recurrent and contentious issue within
the educational and health sphere. Excessive schoolbag weight can lead to back
pain in children, which increases the risk of chronic back pain in adulthood.
There is limited research regarding this among the Maltese paediatric population.
A cross-sectional study was undertaken across all schools in Malta among students
aged 8-13 years (inclusive). Data were collected using a questionnaire detailing
schoolbag characteristics, self-reported pain and demographic variables, such as
age and gender. Structured interviews with participants were also carried out by
physiotherapists. A total of 4005 participants were included in the study, with
20% of the total Malta schoolchildren population. Over 70% of the subjects had a
schoolbag that exceeded the recommended 10% bag weight to body ratio. A total of
32% of the sample complained of back pain, with 74% of these defining it as low
in intensity on the face pain scale-revised. The presence of back pain was
statistically related to gender, body mass index (BMI), school and bag weight to
body weight ratio. After adjusting for other factors, self-reported back pain in
schoolchildren is independently linked to carrying heavy schoolbags. This link
should be addressed to decrease the occurrence of back pain in this age group.
PMID- 28491301
TI - Short- and long-term results of an inpatient programme to manage Complex Regional
Pain Syndrome in children and adolescents.
AB - The aim of this retrospective study was to determine whether an inpatient
approach and the use of regional anaesthesia techniques can accelerate the
recovery to normal functions in children with Complex Regional Pain Syndrome
(CRPS). This study looked at the data of patients admitted to the rehabilitation
unit with a diagnosis of CRPS from January 2010 to April 2015. Variables such as
hospital stay, medications administered, regional anaesthesia procedures, changes
in functional status prior to treatment and at the time of discharge,
psychological evaluation and diagnosis were evaluated. A total of 31 patients (21
females and 10 males) were admitted with a diagnosis of CRPS 1 and 2. In all, 97%
of the patients received a peripheral or central nerve catheter for an average of
4 days with pain scores of Verbal Numeric Scale (VNS) score = 1.0 +/- 0.7 and an
average length of hospital stay of 8.2 +/- 2.6 days. The modified Functional
Independence Measure for Children (WeeFIM) scores and Canadian Association of
Occupational Therapists tests significantly improved at the time of hospital
discharge, as well as their pain scores, which decreased from 8.2 +/- 2 to 1.6 +/
3. In conclusion, these data suggest that the use of regional anaesthesia
techniques and an intensive inpatient rehabilitation programme could accelerate
the recovery of children with CRPS.
PMID- 28491302
TI - Fibromyalgia in Behcet's disease: a narrative review.
AB - INTRODUCTION: Fibromyalgia is characterised by chronic widespread pain and
tenderness. It has often been reported to occur concomitantly with chronic
rheumatological conditions. Behcet's disease is a chronic relapsing, multisystem,
autoinflammatory disease. There is only limited understanding of a potential
relationship between fibromyalgia and Behcet's disease. AIM: Given the potential
detrimental influence of pain on the outcome of chronic disease, the aim of this
narrative review is to gain an understanding of the incidence and presentation of
fibromyalgia in Behcet's disease. METHODS: Electronic databases Scopus, Medline,
PubMed and UpToDate were searched. RESULTS: A total of 269 studies were
identified, and limitations and exclusion/inclusion criteria were applied to
ensure accurate and comparable selection of studies; four studies were selected.
All cases were assessed for the presence of fibromyalgia according to the 1990 or
2010 diagnostic criteria of the American College of Rheumatology, with Behcet's
disease diagnosed according to the International Study Group (ISG) for Behcet's
disease criteria. A higher prevalence of fibromyalgia (5.7-37.1%) was reported in
Behcet's disease compared to that of the general population (2.9-4.7%).
DISCUSSION: While an increased prevalence of fibromyalgia was found in patients
with Behcet's disease, this needs to be considered within the context of limited
available evidence. The potential impact of these conditions on the disease
activity of each other is not clear and may require a prospective study.
CONCLUSION: Fibromyalgia appears to be more prevalent in those with Behcet's
disease than would be expected in the overall population. Significance: This
review provides some evidence that fibromyalgia is more prevalent in those with
Behcet's disease. To ensure appropriate patient treatment choices, it is
important that both conditions are diagnosed where they co-exist.
PMID- 28491303
TI - Self-evaluation of tobacco exposure by allied health students in a community
college setting.
AB - OBJECTIVE: Tobacco education is among the initiatives encouraged for health
professionals to help them appreciate the significance of addressing tobacco use
among their patients. In this pilot study, a nicotine biomarker (cotinine) study
was introduced to an applied microbiology course required of all allied health
students. Participants assessed their own smoking status in the previous 24 h
using a two-dimensional experimental design of a questionnaire and rapid urinary
cotinine immunoassay. The study goals were >90% participation of the home
administered assay and high correlation of the results to cotinine standards.
Allied health students (medical assistants, respiratory therapists, surgical
technicians) were selected as the initial test group. METHODS: The study was
initiated 10 months after the college became 100% tobacco free. Participants were
initially trained on the use and interpretation of the rapid cotinine test using
three cotinine standards (0, 400, and 2000 ng/mL urine). Participants
subsequently tested their own first-morning urine sample at home and then
answered a questionnaire about their tobacco smoke (and/or nicotine) exposure in
the previous 24-h period. RESULTS: The cotinine laboratory was offered to a total
of 161 students (88% female) over 24 months. Participants who reported no
exposure to a nicotine product in any venue made up 55% of the group. Daily
smokers made up 17% of the study participants as confirmed by their elevated
cotinine levels (greater than 100 ng/mL urine). The remaining participants (28%)
either resided with smokers and/or rode in an automobile with an individual
smoking in the previous 24 h. Their cotinine levels were moderately elevated in
some cases, particularly if they had ridden in a car with a smoker. CONCLUSION:
The pilot study met our objectives of >90% participation and high correlation of
urinary cotinine levels with questionnaire self-reports.
PMID- 28491304
TI - Health care to empower self-care in adolescents with type 1 diabetes mellitus and
an immigrant minority background.
AB - BACKGROUND: The pediatric diabetes team aims to support health, quality of life,
and normal growth and development among adolescents with type 1 diabetes
mellitus. Adolescents with an immigrant background have been found less
successful in self-care. Previous research indicated that adolescents who had
integrated the disease as a part of their self-image reasoned differently about
their self-care to those who had not. OBJECTIVE: The aim of this study was to
identify elements in the patient-pediatrician consultations that might influence
such integration of the disease among adolescents with type 1 diabetes mellitus.
METHODS: A total of 12 pediatrician-adolescent consultations were video-recorded
and analyzed. The adolescents all had an immigrant background. RESULTS:
Integration of the disease appeared enabled when responsibility was shared; when
hope, autonomy, and emotions were confirmed; and when the pediatrician asked
probing questions. Letting objective data dominate the adolescent's experiences,
using risk as a motivator, neutralizing emotions in relation to having diabetes,
and confirming forgetfulness, may instead inhibit disease integration.
CONCLUSION: An extended person-centered approach with focus on the adolescent's
experiences of everyday life with a chronic disease and less attention on
physical parameters in the pediatrician-adolescent consultations may increase
integration of the disease.
PMID- 28491306
TI - Association of provider opioid prescribing practices and the Centers for Medicare
and Medicaid Services hierarchical condition category score: A retrospective
examination of correlation between the volume of provider-prescribed opioid
medications and provider panel complexity.
AB - OBJECTIVE: Opioids are being prescribed at increasing rates in primary care
practices, and among individual providers there is significant variability in
opioid prescribing. Primary care practices also vary significantly in complexity
of their patients, ranging from healthy patients to those with multiple
comorbidities. Our objective was to examine individual primary care providers for
an association between their opioid prescribing and the complexity/risk of their
panel of patients (a panel of patients is a group of patients whose medical care
is the responsibility of a specific healthcare provider or care team). METHODS:
We retrospectively examined 12 months of opioid prescription data from a primary
care practice. We obtained counts of opioids prescribed by providers in the Mayo
Clinic, Rochester, Minnesota primary care practice. For patients paneled
(assigned) to family medicine and internal medicine, we used the Centers for
Medicare and Medicaid Services hierarchical condition category patient risk score
as a measure of patient complexity. After adjusting the opioid counts for panel
patient count (to get opioid counts per patient), we used linear regression
analysis to determine the correlation between the hierarchical condition category
risk and the amount of opioid prescribed by individual providers. RESULTS: Among
our combined 103 primary care providers, opioid unit counts prescribed per
patient were highly correlated with the providers' hierarchical condition
category panel risk score (r2 = 0.54). After excluding three outliers, r2 was
0.74. With and without the outliers, the correlation was very significant (p <
0.0001). Subgroup analysis of panels with hierarchical condition category ? 0.45
showed no correlation of opioid prescribing volume with hierarchical condition
category (r2 < 0.02; p = 0.32). Provider panels with hierarchical condition
category > 0.45 showed significant correlation with hierarchical condition
category (r2 = 0.26; p = 0.001). CONCLUSION: When examining differences in
primary care providers' opioid prescribing practices, the Centers for Medicare
and Medicaid Services endorsed risk score (the hierarchical condition category
score) can help adjust for population differences of a provider's patients.
PMID- 28491305
TI - Effects of carvedilol on structural and functional outcomes and plasma biomarkers
in the mouse transverse aortic constriction heart failure model.
AB - INTRODUCTION: Despite the widespread use of the mouse transverse aortic
constriction heart failure model, there are no reports on the characterization of
the standard-of-care agent carvedilol in this model. METHODS: Left ventricular
pressure overload was produced in mice by transverse aortic constriction between
the innominate and left common carotid arteries. Carvedilol was administered at
multiple dose levels (3, 10 and 30 mg/kg/day per os; yielding end-study mean
plasma concentrations of 0.002, 0.015 and 0.044 uM, respectively) in a
therapeutic design protocol with treatment initiated after the manifestation of
left ventricular remodeling at 3 weeks post transverse aortic constriction and
continued for 10 weeks. RESULTS: Carvedilol treatment in transverse aortic
constriction mice significantly decreased heart rate and left ventricular dP/dt
(max) at all dose levels consistent with beta-adrenoceptor blockade. The middle
dose of carvedilol significantly decreased left ventricular weight, whereas the
higher dose decreased total heart, left and right ventricular weight and wet lung
weight compared to untreated transverse aortic constriction mice. The higher dose
of carvedilol significantly increased cardiac performance as measured by ejection
fraction and fractional shortening and decreased left ventricular end systolic
volume consistent with the beneficial effect on cardiac function. End-study
plasma sST-2 and Gal-3 levels did not differ among sham, transverse aortic
constriction control and transverse aortic constriction carvedilol groups. Plasma
brain natriuretic peptide concentrations were elevated significantly in
transverse aortic constriction control animals (~150%) compared to shams in
association with changes in ejection fraction and heart weight and tended to
decrease (~30%, p = 0.10-0.12) with the mid- and high-dose carvedilol treatment.
CONCLUSION: A comparison of carvedilol hemodynamic and structural effects in the
mouse transverse aortic constriction model versus clinical use indicates a strong
agreement in effect profiles preclinical versus clinical, providing important
translational validation for this widely used animal model. The present plasma
brain natriuretic peptide biomarker findings support the measurement of plasma
natriuretic peptides in the mouse transverse aortic constriction model to extend
the translational utility of the model.
PMID- 28491307
TI - Better, Sooner, More Convenient? The reality of pursuing greater integration
between primary and secondary healthcare providers in New Zealand.
AB - OBJECTIVES: This article focuses on the results of evaluations of two business
plans developed in response to a policy initiative which aimed to achieve greater
integration between primary and secondary health providers in New Zealand. We
employ the Consolidated Framework for Implementation Research to inform our
analysis. The Better, Sooner, More Convenient policy programme involved the
development of business plans and, within each business plan, a range of areas of
focus and associated work-streams. METHODS: The evaluations employed a mixed
method multi-level case study design, involving qualitative face-to-face
interviews with front-line staff, clinicians and management in two districts, one
in the North Island and the other in the South Island, and an analysis of routine
data tracked ambulatory sensitive hospitalisations and emergency department
presentations. Two postal surveys were conducted, one focussing on the patient
care experiences of integration and care co-ordination and the second focussing
on the perspectives of health professionals in primary and secondary settings in
both districts. RESULTS: Both evaluations revealed non-significant changes in
ambulatory sensitive hospitalisations and emergency department presentation rates
and slow uneven progress with areas of focus and their associated work-streams.
Our evaluations revealed a range of implementation issues, the barriers and
facilitators to greater integration of healthcare services and the implications
for those who were responsible for putting policy into practice. CONCLUSION: The
business plans were shown to be overly ambitious and compromised by the size and
scope of the business plans; dysfunctional governance arrangements and associated
accountability issues; organisational inability to implement change quickly with
appropriate and timely funding support; an absence of organisational structural
change allowing parity with the policy objectives; barriers that were encountered
because of inadequate attention to organisational culture; competing additional
areas of focus within the same timeframe; and consequent overloading of front
line staff which led to workload stress, fatigue and disillusionment. Where
success was achieved, this largely hinged on the enthusiasm of a small pool of
front-line workers and their initial buy-into the idea of integrated care.
PMID- 28491308
TI - Novel combined patient instruction and discharge summary tool improves timeliness
of documentation and outpatient provider satisfaction.
AB - BACKGROUND: Incomplete or delayed access to discharge information by outpatient
providers and patients contributes to discontinuity of care and poor outcomes.
OBJECTIVE: To evaluate the effect of a new electronic discharge summary tool on
the timeliness of documentation and communication with outpatient providers.
METHODS: In June 2012, we implemented an electronic discharge summary tool at our
145-bed university-affiliated Veterans Affairs hospital. The tool facilitates
completion of a comprehensive discharge summary note that is available for
patients and outpatient medical providers at the time of hospital discharge.
Discharge summary note availability, outpatient provider satisfaction, and time
between the decision to discharge a patient and discharge note completion were
all evaluated before and after implementation of the tool. RESULTS: The
percentage of discharge summary notes completed by the time of first post
discharge clinical contact improved from 43% in February 2012 to 100% in
September 2012 and was maintained at 100% in 2014. A survey of 22 outpatient
providers showed that 90% preferred the new summary and 86% found it
comprehensive. Despite increasing required documentation, the time required to
discharge a patient, from physician decision to discharge note completion,
improved from 5.6 h in 2010 to 4.1 h in 2012 (p = 0.04), and to 2.8 h in 2015 (p
< 0.001). CONCLUSION: The implementation of a novel discharge summary tool
improved the timeliness and comprehensiveness of discharge information as needed
for the delivery of appropriate, high-quality follow-up care, without adversely
affecting the efficiency of the discharge process.
PMID- 28491310
TI - Achieving optimal technology use: A proposed model for health technology
reassessment.
AB - BACKGROUND: Healthcare providers, managers and policy-makers in many
jurisdictions are focused on a common goal: optimizing value and quality of care
provided to their citizens within a resource envelope. Health technology
reassessment is a structured, evidence-based assessment of the clinical, social,
ethical and economic effects of a technology currently used in the healthcare
system to inform optimal use of that technology in comparison with its
alternatives. There are, however, few practical experiences with health
technology reassessment and, as such, a nascent theoretical and methodological
base. Health technology reassessment is a key strategy to achieve optimal
healthcare resource utilization, and establishing a model for health technology
reassessment is a required methodological step. METHODS AND RESULTS: The purpose
of this article is to answer three formative questions: (1) What is health
technology reassessment? (2) When should a health technology reassessment be
implemented? (3) What is the role of health technology reassessment in evidence
informed health policy? Finally, we propose a conceptual framework for health
technology reassessment, which others can modify, adapt, or adopt in their own
context. The model consists of three broad phases and six iterative stages: (1)
identification, (2) prioritization, (3) evidence synthesis, (4) determine
policy/practice recommendation, (5) policy/practice implementation and (6)
monitoring and evaluation. Two foundational components (meaningful stakeholder
engagement and ongoing knowledge exchange and utilization) are represented across
all stages. CONCLUSION: This description of health technology reassessment and
the proposed model can be used by healthcare policy-makers and researchers to
advance the field of technology management, with the goal of achieving optimal
use throughout a technology's lifecycle.
PMID- 28491311
TI - Does increased standardisation in health care mean less responsiveness towards
individual patients' expectations? A register-based study in Swedish primary
care.
AB - OBJECTIVE: We explore whether standardisation in health care based on evidence on
group level and a public health perspective is in conflict with responsiveness
towards individual patient's expectations in Swedish primary care. METHODS: Using
regression analysis, we study the association between patient views about
providers' responsiveness and indicators reflecting provider's adherence to
evidence-based guidelines, controlled for characteristics related to providers,
including patient mix and degree of competition facing providers. Data were taken
from two Swedish regions in years 2012 and 2013. RESULTS: Patients' views about
responsiveness are positively correlated with variables reflecting provider's
adherence to evidence-based guidelines regarding treatment of elderly and risk
groups, drug reviews and prescription of antibiotics. A high overall illness,
private ownership and a high proportion of all visits being with a doctor are
positively associated with patient views about responsiveness. The opposite
relation was found for a high social deprivation among enrolled individuals and
size of practice. There was no systematic variation with respect to the degree of
competition facing providers. CONCLUSION: Results suggest that responsiveness
towards individual patient expectations is compatible with increased
standardisation in health care. This is encouraging for health care providers as
they are challenged to balance increased demands from both patients and payers.
PMID- 28491312
TI - Neuroleptic malignant syndrome following catatonia: Vigilance is the price of
antipsychotic prescription.
AB - OBJECTIVES: To describe a case of neuroleptic malignant syndrome following
antipsychotic treatment of catatonia, highlighting the potentially serious
complications of this rare adverse drug reaction. METHODS: We present a case
report of a patient who developed this syndrome with various sequelae. RESULTS:
The patient developed neuroleptic after being treated with lorazepam and
olanzapine for catatonia. He subsequently developed the complications of
rhabdomyolysis, acute kidney injury, pulmonary embolism, urinary retention and
ileus. He received high-dose lorazepam, anticoagulation and intravenous fluids.
Antipsychotic medication in the form of haloperidol was reinstated with no
adverse effect, and he went on to make a full recovery. CONCLUSIONS: This case
illustrates the potential life-threatening complications of neuroleptic malignant
syndrome and the need for a low index of clinical suspicion. It also highlights
the lack of evidence for treatment of catatonia, including the use of
antipsychotics.
PMID- 28491313
TI - Positron emission tomography imaging in a case of E200K mutation-related
spongiform encephalopathy with non-diagnostic magnetic resonance imaging and
cerebrospinal fluid testing.
AB - OBJECTIVE: Creutzfeldt-Jakob disease is a rapidly progressive spongiform
encephalopathy. The E200K mutation is found in a majority of genetically
transmitted Creutzfeldt-Jakob disease cases. METHODS: We describe the case and
associated neuroimaging of an E200K-129M gene-mutation-related fatal spongiform
encephalopathy with resultant clinical insomnia and thalamic changes. RESULTS: A
46-year-old Caucasian male presented with, who was well until 2 months prior to
admission, a rapidly progressive dementia followed by a change in personality
with auditory and visual hallucinations. His wife noted progressively worsening
jerking and other limb movements and that he kept his eyes open overnight and was
"awake" at all hours. Magnetic resonance imaging, electroencephalogram and
initial cerebrospinal fluid analysis were essentially non-diagnostic. Positron
emission topography revealed severe bilateral thalamic hypometabolism. Posthumous
cerebrospinal fluid analysis revealed abnormal PrP 27-30 protein. Autopsy
confirmed prion disease and presence of the E200K-129M mutation. CONCLUSION: This
report highlights that positron emission topography imaging may help diagnose
E200K-129M mutation-related spongiform encephalopathy. In cases of non-diagnostic
magnetic resonance imaging, electroencephalogram and cerebrospinal fluid studies,
early positron emission topography may help in the workup of rapidly progressive
dementia.
PMID- 28491314
TI - Major depressive disorder with religious struggle and completed suicide after
hair transplantation.
AB - OBJECTIVES: Psychological outcomes of aesthetic surgical procedures like hair
transplantation are mostly positive including decreased anxiety, depression and
social phobia and increased general well-being, self-efficacy and self-esteem.
However, some patients may suffer from post-surgical depression and post-surgical
increased suicide rates have been reported for breast augmentation patients.
Difficulty adapting to the new image, unfulfilled psychological needs expected to
be met by the surgery, side effects of the surgery like tissue swelling or
bruising, uncontrolled pain, presence of body dysmorphic disorder and previous
history of mood disorder may be some of the risk factors for post-surgical
depression. METHODS: Here, we present a case without prior psychiatric history
who developed major depressive disorder after hair transplantation and died of
suicide. RESULTS: He started experiencing religious struggle related to his
decision about the hair transplant which he interpreted as acting against God's
will. While religious involvement has been reported to be a protective factor
against depression, spiritual struggle, which includes religious guilt, has been
described as an important risk factor for depression, hopelessness and
suicidality which might explain the severity of depression in our patient.
CONCLUSIONS: This case highlights the importance of a detailed psychiatric
evaluation and exploration of religious concerns of any patient before any type
of aesthetic surgery. Major depressive disorder is a treatable condition;
however, mild depression can go unnoticed. Religious belief and related religious
practices affect an individual's personal health attitudes; therefore, we think
that every physician is needed to explore the religious concerns of any patient
during any medical examination or surgical procedure. Relevant religious
authorities should be consulted when necessary.
PMID- 28491315
TI - Subcutaneous dirofilariasis caused by Dirofilaria (Nochtiella) repens in Sri
Lanka: A potential risk of transmitting human dirofilariasis.
AB - OBJECTIVE: Dirofilariasis is a parasitic infection caused by filarial nematodes
belonging to the genus Dirofilaria. Human dirofilariasis due to Dirofilaria
repens has been widely reported from European countries. Sri Lanka is the most
affected country in Asia with an infection rate of almost 60% in dog population.
However, human infection of D. repens remains undiagnosed and many of the cases
are not scientifically documented. Therefore, the objective of the present
investigation is to document the presence of dirofilariasis infections in humans.
METHOD: A 1 year and 10 months old boy from Ragama, Gampaha District, Western
Province of Sri Lanka, was presented to a private hospital with a painless, non
pruritic and ill-defined subcutaneous nodule on his right hypochondrial region of
the anterior abdominal wall for 1 week. On examination, there was a non-tender
swelling measuring 2 cm * 2 cm in the anterior abdominal wall, with surrounding
mild redness. The patient was referred for ultrasound confirmation. RESULTS: The
ultrasound scan revealed a hypoechoic nodular lesion measuring 11 mm * 6 mm in
the anterior abdominal wall. Parasitological examination on the excised nodule
confirmed the presence of D. repens measuring 10.5 cm in length having
characteristic cuticle with longitudinal ridges. CONCLUSION: It is essential to
record the human infections and increase the awareness about this infection,
diagnostic tests and vector controlling measures, in order to reduce the disease
prevalence through suppressing vector densities, proper diagnosis and patient
care.
PMID- 28491316
TI - Pituitary abscess in an HIV-1-infected patient.
AB - OBJECTIVES: Pituitary abscess is a rare occurrence among pituitary conditions,
but one which carries life-threatening potential. An immunocompromised status is
a risk factor for the development of a pituitary abscess; however, literature
describes only one case among HIV-infected patients. METHODS AND RESULTS: We
present here a case of pituitary abscess in an HIV-1-positive patient, who
demonstrated a shock status, disturbance of consciousness and generalized skin
rash with laboratory findings of hypovolemia, acute inflammatory reaction and
blood electrolyte abnormality. We first diagnosed the dermal manifestation as
atypical generalized zoster, however, the other clinical findings could not be
explained by VZV infection only. Combination with anamnesis, head magnetic
resonance imaging scan and endocrine function test helped us to diagnose
pituitary abscess. Although the etiology of the pituitary abscess could not be
detected, the patient was successfully treated with antibiotics but followed by
panhypopituitarism as sequela. CONCLUSION: A pituitary abscess should be
considered in HIV-infected patients with endocrinological abnormalities, visual
field defects, and central nervous system infection signs or symptoms, regardless
of CD4 T-cell counts.
PMID- 28491317
TI - Marathoning with myotonic dystrophy type 2 (proximal myotonic myopathy) and
leukopenia.
AB - OBJECTIVES: A mild, slowly progressive course of proximal myotonic myopathy, also
known as myotonic dystrophy type 2, over years allowing the patient to continue
with extreme sport activity, has been only rarely reported. METHODS: Case report.
RESULTS: The patient is a 54-year-old female sport teacher who developed myotonia
of the distal upper limbs at the age of 32 years. Over the following 22 years,
myotonia spreaded to the entire musculature. Myotonia did not prevent her from
doing her job and from marathoning and improved with continuous exercise.
Additionally, she had developed hypothyroidism, ovarial cysts, incipient
cataract, motor neuropathy, hepatopathy, leukopenia, and mild hyper-CK-emia. A
heterozygous CCTG-repeat expansion of 500-9500 was found in the CNBP/ZNF9 gene.
At the age of 54 years, she was still performing sport, without presenting with
myotonia on clinical examination or having developed other typical manifestations
of proximal myotonic myopathy. CONCLUSIONS: This case shows that proximal
myotonic myopathy may take a mild course over at least 22 years, that proximal
myotonic myopathy with mild myotonia may allow a patient to continue strenuous
sport activity, and that continuous physical activity may contribute to the mild
course of the disease.
PMID- 28491318
TI - Recovery of methotrexate-induced anuric acute kidney injury after glucarpidase
therapy.
AB - OBJECTIVES: This case report describes two cases of high-dose methotrexate
induced nephrotoxicity: death in the case of conventional supportive care and
successful renal function recovery in a patient treated with glucarpidase and
continuous dialysis. METHODS: High dose methotrexate is widely used for
management of adult and pediatric malignancies. However, high-dose methotrexate
induced renal nephrotoxicity may cause severe, even lethal complications. Here we
present examples of such outcomes. RESULTS: We present one case of lethal high
dose methotrexate nephrotoxicity in a patient treated with conventional rescue
therapy. We contrast this outcome with another patient with high-dose
methotrexate-induced anuric acute kidney injury, who has recovered renal function
following therapy with glucarpidase and continuous dialysis. CONCLUSIONS: This is
only the second reported case of high-dose methotrexate-induced anuric acute
kidney injury, and the only one with a reported clinical outcome. This first
report of recovery from high-dose methotrexate-induced anuric acute kidney injury
after glucarpidase administration supports available evidence pointing to the
effectiveness of this therapy.
PMID- 28491319
TI - Macroscopic lymphovascular invasion visualized on mammogram and magnetic
resonance imaging: Initially misidentified as ductal carcinoma in situ but
properly diagnosed by immunohistochemistry.
AB - OBJECTIVES: Lymphovascular invasion (LVI) is a pathologic, microscopic finding
associated with invasive cancer, and is a poor prognostic indicator, but has no
reported imaging findings. This report presents the first documented case of LVI
with seen by imaging. Linear branching microcalcifications were identified on
mammography and clumped enhancement was noted on MRI, both imaging findings that
are highly predictive of ductal carcinoma in situ (DCIS). METHODS: Ultrasound
guided core biopsy of the dominant mass was performed, confirming invasive ductal
malignancy. Stereotactic biopsy performed on the microcalcifications was
initially interpreted by pathology as DCIS. RESULTS: Patient underwent
mastectomy. Pathologic evaluation of the surgical specimen confirmed the invasive
ductal malignancy. Microcalcifications were re-evaluated with
immunohistochemistry (IHC) and re-classified as LVI. Radiology images and IHC
stains are shown. CONCLUSION: This is the first report of LVI identified by
imaging with findings that mimicked DCIS and initially mis-identified as DCIS by
pathology as well. The implications of this overlap in radiologic appearance are
discussed.
PMID- 28491320
TI - Push-pull dioxaborine as fluorescent molecular rotor: far-red fluorogenic probe
for ligand-receptor interactions.
AB - Fluorescent solvatochromic dyes and molecular rotors increase their popularity as
fluorogenic probes for background-free detection of biomolecules in cellulo in no
wash conditions. Here, we introduce a push-pull boron-containing (dioxaborine)
dye that presents unique spectroscopic behavior combining solvatochromism and
molecular rotor properties. Indeed, in organic solvents, it shows strong red
shifts in the absorption and fluorescence spectra upon increase in solvent
polarity, typical for push-pull dyes. On the other hand, in polar solvents, where
it probably undergoes Twisted Intramolecular Charge Transfer (TICT), the dye
displays strong dependence of its quantum yield on solvent viscosity, in
accordance to Forster-Hoffmann equation. In comparison to solvatochromic and
molecular rotor dyes, dioxaborine derivative shows exceptional extinction
coefficient (120,000 M-1 cm-1), high fluorescence quantum yields and red/far-red
operating spectral range. It also displays much higher photostability in apolar
media as compared to Nile Red, a fluorogenic dye of similar color. Its reactive
carboxy derivative has been successfully grafted to carbetocin, a ligand of the
oxytocin G protein-coupled receptor. This conjugate exhibits >1000-fold turn on
between apolar 1,4-dioxane and water. It targets specifically the oxytocin
receptor at the cell surface, which enables receptor imaging with excellent
signal-to-background ratio (>130). We believe that presented push-pull
dioxaborine dye opens a new page in the development of fluorogenic probes for
bioimaging applications.
PMID- 28491321
TI - Thermotolerance capacities of native and exotic coastal plants will lead to
changes in species composition under increased heat waves.
AB - With an increase in the frequency and intensity of extreme heat events, plants
are likely to reach their thermal limits and show slower growth or increased
mortality. We investigated differences amongst coastal native and invasive shrubs
and grasses to investigate if particular species might be more at risk in the
future. Using an ecologically relevant experimental set of heat waves over a
month, we assessed changes in biomass and photosynthetic efficiency in a
laboratory setting using 25 coastal Australian species divided into native and
exotic shrubs, and native and exotic grasses. We also compared three C3 and three
C4 grasses within the native and exotic groups. Overall, native shrubs suffered
higher mortality, lower growth and increased photosynthetic stress. There was
some evidence that C3 grasses, had lower growth with heat waves, compared to C4
species although, in general, grasses showed evidence of photosynthetic
acclimation over the month. Increases in leaf abscission suggest that part of the
acclimation process was to develop new, thermally tolerant leaves. Our results
indicate that in the future we would expect an increase in exotic shrubs and
grasses occupying spaces in coastal plant communities that arise from native
mortality following extreme heat events. Management of these coastal communities
will need to focus strongly on maintaining a diverse native shrub composition
that can resist climate-based disturbances (such as wildfire), as well as
controlling the extent and biomass of exotic species, if coastal communities are
to remain healthy and diverse in a changing climate.
PMID- 28491322
TI - ERRATUM.
AB - [This corrects the article DOI: 10.1002/rcr2.230.].
PMID- 28491324
TI - Giant parathyroid adenoma: differential aspects compared to parathyroid
carcinoma.
AB - : The 85% of cases of primary hyperparathyroidism (PHPT) are due to parathyroid
adenomas (PA) and less than 1% to parathyroid carcinomas (PC). The PA usually
measure <2 cm, weigh <1 g and generate a mild PHPT, whereas the PC usually
exceeds these dimensions and are associated with a severe PHPT. However, giant PA
(GPA), which is defined as those larger than 3 g, has been documented. Those may
be associated with very high levels of PTH and calcium. In these cases, their
differentiation before and after surgery with PC is very difficult. We present a
case of severe PHPT associated with a large parathyroid lesion, and we discuss
the differential aspects between the GPA and PC. LEARNING POINTS: In parathyroid
lesions larger than 2 cm, the differential diagnosis between GPA and PC should be
considered.Pre and postsurgical differentiation between GPA and PC is difficult;
however, there are clinical, analytical and radiographic characteristics that may
be useful.The depth/width ratio larger or smaller than 1 seems to be the most
discriminatory ultrasound parameter for the differential diagnosis.Loss of
staining for parafibromin has a specificity of 99% for the diagnosis of PC.The
simultaneous presence of several histological characteristics, according to the
classification of Schantz and Castleman, is frequent in PC and rare in GPA.
PMID- 28491326
TI - NMNI editorial report, 2016.
PMID- 28491325
TI - Propionimicrobium lymphophilum and Actinotignum schaalii bacteraemia: a case
report.
AB - Propionimicrobium lymphophilum is an anaerobic Gram-positive bacillus that exists
in human skin and urinary tract. The pathogenicity is, however, not well known.
Only two cases of urinary tract infection have been described recently. In the
case presented here, the bacterium was isolated, concomitant with Actinotignum
schaalii, from blood culture of a patient with fever and difficulty of urination.
The bacteria were identified by matrix-assisted laser desorption/ionization time
of-flight mass spectrometry and 16S rRNA sequencing. The case was successfully
treated with ampicillin/sulbactam.
PMID- 28491323
TI - Interactions between oestrogen and 1alpha,25(OH)2-vitamin D3 signalling and their
roles in spermatogenesis and spermatozoa functions.
AB - Oestrogens and 1alpha,25(OH)2-vitamin D3 (1,25-D3) are steroids that can provide
effects by binding to their receptors localised in the cytoplasm and in the
nucleus or the plasma membrane respectively inducing genomic and non-genomic
effects. As confirmed notably by invalidation of the genes, coding for their
receptors as tested with mice with in vivo and in vitro treatments, oestrogens
and 1,25-D3 are regulators of spermatogenesis. Moreover, some functions of
ejaculated spermatozoa as viability, DNA integrity, motility, capacitation,
acrosome reaction and fertilizing ability are targets for these hormones. The
studies conducted on their mechanisms of action, even though not completely
elicited, have allowed the demonstration of putative interactions between their
signalling pathways that are worth examining more closely. The present review
focuses on the elements regulated by oestrogens and 1,25-D3 in the testis and
spermatozoa as well as the interactions between the signalling pathways of both
hormones.
PMID- 28491327
TI - Understanding perceived determinants of nurses' eating and physical activity
behaviour: a theory-informed qualitative interview study.
AB - BACKGROUND: Unhealthy eating and physical activity behaviours are common among
nurses but little is known about determinants of eating and physical activity
behaviour in this population. The present study used a theoretical framework
which summarises the many possible determinants of different health behaviours
(the Theoretical Domains Framework; TDF) to systematically explore the most
salient determinants of unhealthy eating and physical activity behaviour in
hospital-based nurses. METHODS: Semi-structured qualitative interviews based on
the TDF were conducted with nurses (n = 16) to explore factors that behavioural
theories suggest may influence nurses' eating and physical activity behaviour.
Important determinants of the target behaviours were identified using both
inductive coding (of categories emerging from the data) and deductive coding (of
categories derived from the TDF) of the qualitative data. RESULTS: Thirteen of
the fourteen domains in the TDF were found to influence nurses' eating and
physical activity behaviour. Within these domains, important barriers to engaging
in healthy eating and physical activity behaviour were shift work, fatigue,
stress, beliefs about negative consequences, the behaviours of family and friends
and lack of planning. Important factors reported to enable engagement with
healthy eating and physical activity behaviours were beliefs about benefits, the
use of self-monitoring strategies, support from work colleagues, confidence,
shift work, awareness of useful guidelines and strategies, good mood, future
holidays and receiving compliments. CONCLUSIONS: This study used a theory
informed approach by applying the TDF to identify the key perceived determinants
of nurses' eating and physical activity behaviour. The findings suggest that
future efforts to change nurses' eating and physical activity behaviours should
consider targeting a broad range of environmental, interpersonal and
intrapersonal level factors, consistent with a socio-ecological perspective.
PMID- 28491328
TI - Increases in waist circumference independent of weight in Mongolia over the last
decade: the Mongolian STEPS surveys.
AB - BACKGROUND: In Mongolia, mean waist circumference (WC) has increased dramatically
over the last decade, however, it is unknown whether these increases have been
greater than corresponding increases in weight. In this study we aimed to assess
whether recent increases in WC were greater than expected from changes in weight
in Mongolian adults. METHODS: We used data on 13260 Mongolian adults, aged
between 18 and 64 years, who participated in one of three (2005, 2009, 2013)
nationally representative cross-sectional surveys. Linear regression was used to
estimate changes in mean WC over time, adjusted for age, sex, height and weight.
We also estimated the age-standardised prevalence for four obesity classification
categories (not obese; obese by WC only; obese by body mass index (BMI) only;
obese by both BMI and WC) at each survey year. RESULTS: The estimated mean WC in
2009 and 2013, respectively, was 1.26 cm (95% CI: 0.35 to 2.17) and 1.88 cm (95%
CI: 1.09 to 2.67) greater compared to 2005, after adjusting for age, sex, height
and weight. Between 2005 and 2013, the age-standardised prevalence of those obese
according to both BMI and WC increased from 8.0 to 13.6% for men and from 16.5 to
25.5% for women. During the same period, the percentage who were obese by WC only
increased from 1.8 to 4.8% for men and from 16.5 to 26.8% for women. In contrast,
the percentage who were obese by BMI only remained relatively stable (women: 2.4%
in 2005 to 1.0% in 2013; men: 2.7% in 2005 to 4.0% in 2013). CONCLUSION: Over the
last decade, among Mongolian adults, there has been substantially greater
increase in WC and the prevalence of abdominal obesity than would be expected
from increases in weight. Women are at greater risk than men of being
misclassified as not obese if obesity is defined using BMI only. Obesity should
be monitored using WC in addition to BMI to ensure the prevalence of obesity is
not underestimated.
PMID- 28491329
TI - Varicella vasculopathy presenting with thunderclap headache.
AB - Our report serves to highlight Varicella vasculopathy as a rarity not to be
overlooked in the differential diagnosis of subarachnoid haemorrhage.
PMID- 28491330
TI - Duodenal perforation as a complication of gastrostomy tube migration.
AB - Gastrostomy tube placement is a routinely safe procedure; however, this report
and its accompanying images highlight a rare but serious complication of tube
migration - duodenal perforation.
PMID- 28491331
TI - MPO-C-ANCA-associated necrotising and crescentic glomerulonephritis.
AB - The patterns of ANCA staining usually relate closely to antibodies against
myeloperoxidase and proteinase-3. C-ANCA is mainly antibodies to proteinase-3 and
P-ANCA is antibodies to myeloperoxidase. C-ANCA with antibodies to MPO with
clinical sequelae is unusual.
PMID- 28491332
TI - Lipoma in the femoral triangle.
AB - The differential diagnosis of a lipoma in the femoral region will include a
femoral hernia and vice-versa or both may coexist.
PMID- 28491333
TI - Burkholderia cepacia complex and limited cutaneous vasculitis in patients with
cystic fibrosis: a case series.
AB - There is a high association of reactive skin presentations, mainly limited
cutaneous vasculitis in patients with cystic fibrosis and Burkholderia cepcia
complex chronic infection. This may be due to raised levels of circulating
inflammatory mediators.
PMID- 28491334
TI - Increasing the Rate of Living Donor Kidney Transplantation in Ontario: Donor- and
Recipient-Identified Barriers and Solutions.
AB - PURPOSE OF REVIEW: To hear from living kidney donors and recipients about what
they perceive are the barriers to living donor kidney transplantation, and how
patients can develop and lead innovative solutions to increase the rate and
enhance the experiences of living donor kidney transplantation in Ontario.
SOURCES OF INFORMATION: A one-day patient-led workshop on March 10th, 2016 in
Toronto, Ontario. METHODS: Participants who were previously engaged in priority
setting exercises were invited to the meeting by patient lead, Sue McKenzie. This
included primarily past kidney donors, kidney transplant recipients, as well as
researchers, and representatives from renal and transplant health care
organizations across Ontario. KEY FINDINGS: Four main barriers were identified:
lack of education for patients and families, lack of public awareness about
living donor kidney transplantation, financial costs incurred by donors, and
health care system-level inefficiencies. Several novel solutions were proposed,
including the development of a peer network to support and educate patients and
families with kidney failure to pursue living donor kidney transplantation;
consistent reimbursement policies to cover donors' out-of-pocket expenses; and
partnering with the paramedical and insurance industry to improve the efficiency
of the donor and recipient evaluation process. LIMITATIONS: While there was a
diversity of experience in the room from both donors and recipients, it does not
provide a complete picture of the living kidney donation process for all Ontario
donors and recipients. The discussion was provincially focused, and as such, some
of the solutions suggested may already be in practice or unfeasible in other
provinces. IMPLICATIONS: The creation of a patient-led provincial council was
suggested as an important next step to advance the development and implementation
of solutions to overcome patient-identified barriers to living donor kidney
transplantation.
PMID- 28491335
TI - The Risk of Acute Rejection Following Kidney Transplant by 25-Hydroxyvitamin D
and 1,25-Dihydroxyvitamin D Status: A Prospective Cohort Study.
AB - BACKGROUND: Prediction of acute kidney transplant rejection remains imperfect
despite several known risk factors. There is an increasing appreciation of the
potential importance of the vitamin D pathway in immunological disease and
transplantation. OBJECTIVE: The purpose of this study was to determine the
association of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D with acute
rejection. DESIGN: This was a prospective cohort study. SETTING: Three academic
adult kidney transplant programs in Ontario, Canada, were chosen. PATIENTS: All
consecutive adult patients at the 3 institutions who received a solitary kidney
transplant, were able to provide written informed consent, and planned to be
followed at the same center post-operatively were included. MEASUREMENTS: Serum
concentration of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured at
baseline, 3, and 6 months post-transplantation. Acute rejection was classified
using Banff criteria. METHODS: The co-primary outcome was the association between
25-hydroxyvitamin D or 1,25-dihydroxyvitamin D and time to first occurrence of
biopsy-proven acute rejection (BPAR) within the first year after kidney
transplantation. Cox proportional hazards models were fitted taking into account
the time-varying nature of serum concentrations of 25-hydroxyvitamin D and 1,25
dihydroxyvitamin D. RESULTS: From 556 screened patients, data on 327 kidney
transplant recipients are included. First BPAR occurred in 54 (16.5%) patients.
In adjusted Cox proportional hazards models, the serum concentration of 25
hydroxyvitamin D and 1,25-dihydroxyvitamin D was not associated with acute renal
transplant rejection (hazard ratio 1.00; 95% [confidence interval] CI, 0.87-1.14,
per 10 nmol/L increase, and hazard ratio 0.97; 95% CI, 0.84-1.12, per 10 pmol/L
increase, respectively). LIMITATIONS: Given the observational design, we cannot
rule out the possibility of residual confounding that limited our ability to
detect a clinically significant effect of vitamin D metabolites on acute
rejection. CONCLUSIONS: A low serum concentration of 25-hydroxyvitamin D and 1,25
dihydroxyvitamin D is not associated with an increased risk of acute kidney
transplant rejection following kidney transplantation.
PMID- 28491336
TI - Opportunities for Engaging Patients in Kidney Research.
AB - PURPOSE: The purpose of this review is to provide a summary of the rationale for
engaging patients in research as well as to review the established and envisioned
advantages and strategies for patient-researcher partnerships. The authors of
this article, which include a patient and 4 researchers in kidney disease,
discuss the expected benefits and opportunities for patient engagement in their
respective research programs. The 4 research programs span the spectrum of kidney
disease and focus on enhancing bone health, increasing living donor kidney
transplants, improving medication adherence, and preventing kidney transplant
rejection. SOURCES OF INFORMATION: The sources of information for this review
include published studies on the topics of patient engagement and the 4 research
programs of the new investigators. KEY FINDINGS: (1) Patient, health care
provider, and researcher partnerships can contribute useful insights capable of
enhancing research in kidney disease. (2) Regardless of the research program,
there are various strategies and opportunities for engagement of patients with
lived experience across the various stages of research in kidney disease. (3)
Envisioned advantages of patient-researcher partnerships include: targeting
patient-identified research priorities, integrating patients' experiential
knowledge, improving study design and feasibility through patient-researcher
input, facilitating dissemination of research findings to other patients,
effectively responding to patient concerns about studies, and inspiring
researchers to conduct their research. LIMITATIONS: The limitations of the
current review include the relative scarcity of literature on patient engagement
within the field of kidney disease. IMPLICATIONS: The findings of the current
review suggest that it will be important for future studies to identify optimal
strategies for patient engagement in setting research priorities, study design,
participant recruitment, execution of research projects, and knowledge
dissemination and translation.
PMID- 28491337
TI - Kidney Disease Among Registered Metis Citizens of Ontario: A Population-Based
Cohort Study.
AB - BACKGROUND: Indigenous peoples in Canada have higher rates of kidney disease than
non-Indigenous Canadians. However, little is known about the risk of kidney
disease specifically in the Metis population in Canada. OBJECTIVE: To compare the
prevalence of chronic kidney disease and incidence of acute kidney injury and end
stage kidney disease among registered Metis citizens in Ontario and a matched
sample from the general Ontario population. DESIGN: Population-based,
retrospective cohort study using data from the Metis Nation of Ontario's
Citizenship Registry and administrative databases. SETTING: Ontario, Canada; 2003
2013. PATIENTS: Ontario residents >=18 years. MEASUREMENTS: Prevalence of chronic
kidney disease and incidence of acute kidney injury and end-stage kidney disease.
Secondary outcomes among patients hospitalized with acute kidney injury included
non-recovery of kidney function and mortality within 1 year of discharge.
METHODS: Database codes and laboratory values were used to determine study
outcomes. Metis citizens were matched (1:4) to Ontario residents on age, sex, and
area of residence. The analysis included 12 229 registered Metis citizens and 48
916 adults from the general population. RESULTS: We found the prevalence of
chronic kidney disease was slightly higher among Metis citizens compared with the
general population (3.1% vs 2.6%, P = 0.002). The incidence of acute kidney
injury was 1.2 per 1000 person-years in both Metis citizens and the general
population (P = 0.54). Of those hospitalized with acute kidney injury, outcomes
were similar among Metis citizens and the general population except 1-year
mortality, which was higher for Metis citizens (24.5% vs 15.3%, P = 0.03). The
incidence of end-stage kidney disease did not differ between groups (<3.0 per 10
000 person-years, P = 0.73). LIMITATIONS: The Metis Nation of Ontario Citizenship
Registry only captures about 20% of Metis people in Ontario. Administrative
health care codes used to identify kidney disease are highly specific but have
low sensitivity. CONCLUSIONS: Rates of kidney disease were similar or slightly
higher for Metis citizens in Ontario compared with the matched general
population.
PMID- 28491338
TI - Setting New Directions for Research in Childhood Nephrotic Syndrome: Results From
a National Workshop.
AB - BACKGROUND: We report on the proceedings of a national workshop held in Canada
with the aims to identify priorities for research in childhood nephrotic syndrome
and to develop a national strategy to address these priorities. METHODS: A
diverse group of participants attended the meeting, including patients, family
members, researchers, and health care providers. We used small group discussions
to explore priorities as perceived by patients and families and by health care
providers and researchers. RESULTS: Research evaluating glucocorticoid
minimization or glucocorticoid-sparing regimens was a consistent theme in the
patient and family discussion group. Families also indicated the need for precise
prognostic information at diagnosis, more information to help them choose the
best available therapy, and more resources for disease management. Health care
providers emphasized the importance of better disease characterization including
genotyping and phenotyping patients, better understanding the pathogenesis, and
the need of providing targeted therapy and precise prognostic information.
CONCLUSIONS: These priorities will inform the development and future directions
of the Canadian Childhood Nephrotic Syndrome (CHILDNEPH) project, a national
research initiative to improve care and outcomes of patients with childhood onset
nephrotic syndrome.
PMID- 28491339
TI - The Clinical Epidemiology and 30-Day Outcomes of Emergency Department Patients
With Acute Kidney Injury.
AB - BACKGROUND: Acute kidney injury (AKI) is associated with increased mortality and
dialysis in hospitalized patients but has been little explored in the emergency
department (ED) setting. OBJECTIVE: The objective of this study was to describe
the risk factors, prevalence, management, and outcomes in the ED population, and
to identify the proportion of AKI patients who were discharged home with no renal
specific follow-up. DESIGN: This is a retrospective cohort study using
administrative and laboratory databases. SETTING: Two urban EDs in Vancouver,
British Columbia, Canada. PATIENTS: We included all unique ED patients over a 1
week period. METHODS: All patients had their described demographics,
comorbidities, medications, laboratory values, and ED treatments collected. AKI
was defined pragmatically, based upon accepted guidelines. The cohort was then
probabilistically linked to the provincial renal database to ascertain renal
replacement (transplant or dialysis) and the provincial vital statistics database
to obtain mortality. The primary outcome was the prevalence of AKI; secondary
outcomes included (1) the proportion of AKI patients who were discharged home
with no renal-specific follow-up and (2) the combined 30-day rate of death or
renal replacement among AKI patients. RESULTS: There were 1651 ED unique
patients, and 840 had at least one serum creatinine (SCr) obtained. Overall, 90
patients had AKI (10.7% of ED patients with at least one SCr, 95% confidence
interval [CI], 8.7%-13.1%; 5.5% of all ED patients, 95% CI, 4.4%-6.7%) with a
median age of 74 and 70% male. Of the 31 (34.4%) AKI patients discharged home, 4
(12.9%) had renal-specific follow-up arranged in the ED. Among the 90 AKI
patients, 11 died and none required renal replacement at 30 days, for a combined
outcome of 12.2% (95% CI, 6.5%-21.2%). LIMITATIONS: Sample sizes may be small.
Nearly half of ED patients did not obtain an SCr. Many patients did not have
sequential SCr testing, and a modified definition of AKI was used.
PMID- 28491340
TI - The Financial Impact of Advanced Kidney Disease on Canada Pension Plan and
Private Disability Insurance Costs.
AB - BACKGROUND: Many working-age individuals with advanced chronic kidney disease
(CKD) are unable to work, or are only able to work at a reduced capacity and/or
with a reduction in time at work, and receive disability payments, either from
the Canadian government or from private insurers, but the magnitude of those
payments is unknown. OBJECTIVE: The objective of this study was to estimate
Canada Pension Plan Disability Benefit and private disability insurance benefits
paid to Canadians with advanced kidney failure, and how feasible improvements in
prevention, identification, and early treatment of CKD and increased use of
kidney transplantation might mitigate those costs. DESIGN: This study used an
analytical model combining Canadian data from various sources. SETTING AND
PATIENTS: This study included all patients with advanced CKD in Canada, including
those with estimated glomerular filtration rate (eGFR) <30 mL/min/m2 and those on
dialysis. MEASUREMENTS: We combined disability estimates from a provincial kidney
care program with the prevalence of advanced CKD and estimated disability
payments from the Canada Pension Plan and private insurance plans to estimate
overall disability benefit payments for Canadians with advanced CKD. RESULTS: We
estimate that Canadians with advanced kidney failure are receiving disability
benefit payments of at least Can$217 million annually. These estimates are
sensitive to the proportion of individuals with advanced kidney disease who are
unable to work, and plausible variation in this estimate could mean patients with
advanced kidney disease are receiving up to Can$260 million per year. Feasible
strategies to reduce the proportion of individuals with advanced kidney disease,
either through prevention, delay or reduction in severity, or increasing the rate
of transplantation, could result in reductions in the cost of Canada Pension Plan
and private disability insurance payments by Can$13.8 million per year within 5
years. LIMITATIONS: This study does not estimate how CKD prevention or increasing
the rate of kidney transplantation might influence health care cost savings more
broadly, and does not include the cost to provincial governments for programs
that provide income for individuals without private insurance and who do not
qualify for Canada Pension Plan disability payments. CONCLUSIONS: Private
disability insurance providers and federal government programs incur high costs
related to individuals with advanced kidney failure, highlighting the
significance of kidney disease not only to patients, and their families, but also
to these other important stakeholders. Improvements in care of individuals with
kidney disease could reduce these costs.
PMID- 28491342
TI - Hair cortisol and lifetime discrimination: Moderation by subjective social
status.
AB - Discrimination has been associated with elevated cortisol as measured in saliva,
blood, and urine. This study investigated the association between lifetime
discrimination and hair cortisol concentrations, considered a measure of chronic
stress. We recruited 180 young adults from diverse backgrounds. Participant
responses to lifetime discrimination, home stress, and subjective status measures
were recorded. Lifetime discrimination significantly predicted hair cortisol
concentrations, supporting past research that discrimination experiences impact
neuroendocrine systems. To our knowledge, these are the first findings
associating hair cortisol concentrations with discrimination and supports prior
evidence positing discrimination as a chronic stressor that serves as a risk
factor for chronic disease.
PMID- 28491343
TI - Corrigendum.
AB - [This corrects the article DOI: 10.1177/2055102916650093.].
PMID- 28491341
TI - Validation of the Kidney Failure Risk Equation in Manitoba.
AB - BACKGROUND: Patients with chronic kidney disease (CKD) are at risk to progress to
kidney failure. We previously developed the Kidney Failure Risk Equation (KFRE)
to predict progression to kidney failure in patients referred to nephrologists.
OBJECTIVE: The objective of this study was to determine the ability of the KFRE
to discriminate which patients will progress to kidney failure in an unreferred
population. DESIGN: A retrospective cohort study was conducted using
administrative databases. SETTING: This study took place in Manitoba, Canada.
MEASUREMENTS: Age, sex, estimated glomerular filtration rate (eGFR), and urine
albumin-to-creatinine ratio (ACR) were measured. METHODS: We included patients
from the Diagnostic Services of Manitoba database with an eGFR <60 mL/min/1.73 m2
and ACR measured between October 2006 and March 2007. Five-year kidney failure
risk was predicted using the 4-variable KFRE and compared with treated kidney
failure events from the Manitoba Renal Program database. Sensitivity and
specificity for KFRE risk thresholds (3% and 10% over 5 years) were compared with
eGFR thresholds (30 and 45 mL/min/1.73 m2). RESULTS: Of 1512 included patients,
151 developed kidney failure over the 5-year follow-up period. The 4-variable
KFRE showed a superior prognostic discrimination compared with eGFR alone (area
under the receiver operating characteristic curve [AUROC] values, 0.90 [95%
confidence interval {CI}: 0.88-0.92] for KFRE vs 0.78 [95% CI: 0.74-0.83] for
eGFR). At a 3% threshold over 5 years, the KFRE had a sensitivity of 97% and a
specificity of 62%. At 10% risk, sensitivity was 86%, and specificity was 80%.
LIMITATIONS: Only 11.7% of stage 3-5 CKD patients had simultaneous ACR
measurement. The KFRE does not account for other indications for referral such as
suspected glomerulonephritis, polycystic kidney disease, and recurrent stone
disease. CONCLUSIONS: The KFRE has been validated in a population with a
demographic and referral profile heretofore untested and performs well at
predicting 5-year risk of kidney failure in a population-based sample of
Manitobans with CKD stages 3 to 5. Thresholds of 3% and 10% over 5 years are
sensitive, specific, and can be used in clinical decision making. Further testing
of the 4-variable KFRE and these thresholds in clinical practice should be
considered.
PMID- 28491344
TI - Use of sildenafil citrate in a cat with Eisenmenger's syndrome and an atrial
septal defect.
AB - A 2-year-old male neutered Siamese cat presenting with weakness and dyspnoea was
diagnosed with an atrial septal defect and pulmonary hypertension, which resulted
in right-to-left shunting (Eisenmenger's syndrome). The cat was treated with
sildenafil (0.25-0.6 mg/kg) for 10 months. There were no apparent treatment
related adverse effects. Improvement in clinical signs was noted, although
increasing doses of sildenafil were required. After 10 months the cat
significantly deteriorated and was euthanased.
PMID- 28491345
TI - Management of a complete uterine prolapse in a cat.
AB - A young female cat was presented with a protrusion of the uterus through the
vulvar lips. The cat had a history of recent parturition, with delivery without
incident of three kittens 48 h earlier. No fetus was found in the uterus. The
protruding uterus was amputated and a staged ovariohysterectomy was performed.
The day after surgery, the queen was healthy with no evidence of vulvar
discharge. Two months later, the owner reported that the queen was clinically
normal with no recurrence of clinical signs.
PMID- 28491346
TI - Metabolic bone disease and central retinal degeneration in a kitten due to
nutritional inadequacy of an all-meat raw diet.
AB - A 5-month-old castrated male Sphynx kitten presented with left hindlimb lameness
shortly after adoption. Prior to adoption, the breeder had fed the kitten an
exclusively raw chicken diet. Radiographs revealed generalized osteopenia and a
left tibia-fibula fracture. Ophthalmic examination revealed corneal
vascularization and opacity in the right eye, and lesions suggestive of feline
central retinal degeneration in the left eye. The patient's diagnoses included
metabolic bone disease and feline central retinal degeneration, which can result
from taurine deficiency. The kitten's nutritional diseases were managed with a
complete and balanced canned diet designed for kitten growth and with taurine
supplementation.
PMID- 28491347
TI - Feline familial pedal eosinophilic dermatosis in two littermates.
AB - In cats, the most common eosinophilic dermatoses are feline miliary dermatitis
and eosinophilic granuloma complex. The most commonly identified underlying cause
is a hypersensitivity reaction. Few cases of familial forms of eosinophilic
dermatoses are reported in the literature. Two young adult cats from the same
litter presented 2 years apart with a severe and chronic fluid or tissue
infiltration of the distal part of several limbs. Lesions started on the forelegs
and developed on the other limbs. Cytological and histopathological examinations
showed lesions consistent with an atypical form of feline eosinophilic dermatosis
associated with secondary bacterial infection. In both cats, antibiotics combined
with immunosuppressive treatment partially improved the lesions, which continued
to progress on a waxing and waning course, even in the absence of treatment.
Allergy work-up did not permit the identification of an underlying allergic
triggering factor. The severity of the lesions, the unusual presentation and the
unsatisfactory response to immunosuppressive therapy in two feline littermates
suggested a genetic form of eosinophilic dermatosis.
PMID- 28491348
TI - A case of feline systemic reactive angioendotheliomatosis.
AB - A 3-year-old domestic shorthair cat presented with lethargy and anorexia. A blood
test showed regenerative anaemia and thrombocytopenia. Thoracic radiographs
showed a small amount of pleural effusion. The cat did not respond to treatment
and died on the fifth day. Necropsy revealed moderate pericardial effusion, and
multifocal coalescing haemorrhages were observed on both atria. Histological
analysis revealed that the most severe lesions were located on the heart.
Numerous arterioles supplying the heart were partially to completely filled with
plump spindle cells that often formed glomerulus-like arrangements within the
lumen. Similar vascular proliferative lesions were also found in the liver,
pancreas and kidney. Immunohistochemical analysis showed that these intraluminal
proliferative spindle cells were positive for anti-von Willebrand factor (vWF).
Strongly positive antismooth muscle actin staining was observed at the periphery
of these intraluminal proliferations (comprising arteriolar smooth muscle) and
certain intraluminal cells (pericytes). The intraluminal thrombi were also
positive for vWF. Those thrombi were confirmed as platelet thrombi by
phosphotungstic acid haematoxylin and Masson's trichrome staining. These results
were consistent with feline systemic reactive angioendotheliomatosis.
PMID- 28491350
TI - JFMS Open Reports - a new platform for high-quality case reports and
national/regional data relevant to feline practice.
PMID- 28491349
TI - Malignant transformation of a duodenal duplication cyst in a cat.
AB - CASE SUMMARY: A 15-year-old domestic shorthair cat presented for lethargy,
vomiting and anorexia. Abdominal ultrasound showed a bi-lobed cystic duodenal
mass. Based on ultrasonographic features, malignant transformation of a duodenal
duplication cyst was suspected. A resection and anastomosis was performed.
Histology of the mass was consistent with carcinoma and an intestinal mucosa was
present along the inner surface of the mass, suggestive of a duplication cyst.
The patient returned 3 months postsurgery with recurrence of clinical signs.
Abdominal ultrasound showed a recurrent duodenal mass at the surgery site and
body wall nodules. Fine-needle aspirates of these lesions showed epithelial
neoplasia. Owing to the poor prognosis, the owners elected euthanasia. RELEVANCE
AND NOVEL INFORMATION: Malignant transformation of duplication cysts in cats is
rare but can be detected on ultrasound. The described ultrasonographic features
can aid in prioritization of malignant transformation of duplication cysts as a
differential diagnosis.
PMID- 28491351
TI - Endophthalmitis due to an intra-ocular linear foreign body in a cat.
AB - CASE SUMMARY: An unusual case of an intraocular linear foreign body that migrated
from the oral cavity, causing a severe endophthalmitis, in a cat is described. A
2-year-old female domestic shorthair cat presented with signs of infection from
the left eye that had begun 2 weeks previously. Despite having been prescribed
oral and topical antibiotics, there was a progressive worsening of the clinical
signs. On ophthalmic examination the cat presented with severe endophthalmitis,
secondary glaucoma and exposure keratitis of the left eye. Radiography
demonstrated the presence of an intraocular linear metallic foreign body
compatible with a sewing needle. During enucleation, when the globe was
extracted, the sewing needle stayed in the orbit. When the needle was pulled
away, a piece of thread was also retrieved, which demonstrated that the linear
foreign body had migrated retrogradely from the oral cavity to the orbit through
the pterygopalatine fossa. Surgical recovery was uneventful. RELEVANCE AND NOVEL
INFORMATION: Intraocular foreign bodies may present in a variety of ways, which
may hinder their clinical detection. The management and prognosis depend on the
composition and location of the foreign body, as well as the possible presence of
secondary infection. To the author's knowledge, this is the first time that a
case of severe endophthalmitis following retrograde intraocular migration of a
linear foreign body from the oral cavity to the orbit through the pterygopalatine
fossa in a cat has been reported.
PMID- 28491352
TI - Fibrosarcoma of the urinary bladder in a cat.
AB - CASE SUMMARY: A 5-year-old female spayed domestic shorthair cat was presented
with haematuria, pollakiuria and stranguria of 2 months' duration, and a firm non
painful mass in the urinary bladder was palpated. Abdominal radiographs showed
thickening and irregular cranial margins of the urinary bladder wall. Abdominal
ultrasound showed a vascularised mass of mixed echogenicity almost entirely
occupying the urinary bladder lumen. During explorative laparotomy, the mass
appeared pedunculated and was totally excised. Histopathology was characterised
by infiltration of the mucosal, submucosal and muscular layers by proliferated
atypical mesenchymal cells; immunochemistry confirmed the diagnosis of
fibrosarcoma. The cat was discharged with normal urination 5 days after surgery.
The owner declined any imaging follow-up but reported the cat to be free of any
clinical signs at 16 months after surgery. RELEVANCE AND NOVEL INFORMATION: To
the best of our knowledge, this is the first case of primary fibrosarcoma of the
urinary bladder in the cat. Fibrosarcoma should be included in the differential
diagnosis of urinary bladder neoplasia.
PMID- 28491353
TI - Multiple acquired portosystemic shunts in a cat secondary to chronic
diaphragmatic rupture.
AB - CASE SUMMARY: A cat with a chronic diaphragmatic rupture presented with
neurological signs, including twitching and focal seizures. Blood ammonia level
was markedly elevated and therefore neurological signs were thought to be related
to hepatic encephalopathy. Exploratory laparotomy revealed that the left lateral
and medial liver lobes were herniated into the thorax and multiple acquired
portosystemic shunts (MAPSS) were present. The hernia was reduced and the
diaphragm repaired. Neurological signs gradually resolved following surgery and 1
year postoperatively the cat was clinically normal, was not on any medication and
had no evidence of hepatic dysfunction. RELEVANCE AND NOVEL INFORMATION: This is
the first report of a chronic diaphragmatic rupture leading to MAPSS in a cat.
PMID- 28491354
TI - Probable vasovagal reaction following cystocentesis in two cats.
AB - CASE SUMMARY: This case report describes an acute reaction, thought to be vagally
mediated, in two cats immediately following cystocentesis. Both cats were being
evaluated for feline idiopathic cystitis and developed bradycardia,
hypersalivation, urination and weakness after a blind cystocentesis. Both cats
recovered uneventfully with supportive care. RELEVANCE AND NOVEL INFORMATION: A
vagally mediated response may occur in cats after cystocentesis, which is a
common procedure performed by veterinary professionals in cats. This response may
be very profound and dramatic. Affected cats will likely make an uneventful
recovery. This vagally mediated response to cystocentesis, though reported by
word of mouth among veterinarians, has not been described in the literature. This
is the first documentation of its occurrence in cats.
PMID- 28491356
TI - Rapid vascular uptake of contrast during a retrograde urethro-cystogram in a cat
with chronic lower urinary tract disease.
AB - CASE SUMMARY: A 9-year male neutered domestic longhair cat was referred to our
hospital for investigation of recurrent urinary tract obstruction. The clinical
signs had started 12 months earlier and the cat had been catheterised on multiple
occasions. Clinical examination and abdominal ultrasound of the abdomen was
unremarkable but examination of the penis revealed it to be prolapsed and
extremely erythematous and friable. A retrograde contrast urethrocystogram was
performed, showing extravasation of the contrast medium and establishing the
presence of partial leakage or a tear of the urethra. In subsequent radiographs,
the contrast was seen being rapidly absorbed into the pelvic and systemic
vasculature via the penile veins, internal and external pudendal veins, internal
and external iliac veins, and, ultimately, the caudal vena cava. Later, the
contrast medium was seen within the renal pelves. Retrograde urethrocystography
revealed stenosis and irregularities of the caudal urethral mucosa consistent
with strictures. A routine perineal urethrostomy was performed and the cat
recovered well. CONCLUSIONS AND RELEVANCE: Rapid vascular absorption of
extravasated contrast medium has not been reported before. In this case, the
increased blood supply to the distal urethra and penis is likely secondary to
(chronic) inflammation, as demonstrated by the urethral strictures and the
friable, oedematous nature of the penis. Whether the inflammation was caused by
chronic obstruction or repeated iatrogenic trauma, or a combination of these
factors, will remain debatable. Nonetheless, this case demonstrates that when a
retrograde contrast urethrocystogram is considered, it is imperative that a
contrast medium (or other intraurethral medication such as local anaesthesia) is
chosen that is safe for intravascular use. Equally, an absolute aseptic technique
is essential considering the potential for contaminants to be absorbed quite
rapidly into the systemic circulation. Multiple catheterisations should be
avoided when there is chronic inflammation, and alternative options should be
considered when chronic disease is suspected.
PMID- 28491355
TI - Otogenic meningoencephalomyelitis due to Cryptococcus gattii (VGII) infection in
a cat from Western Australia.
AB - CASE SUMMARY: A 7-year-old spayed domestic longhair cat from Perth, Western
Australia, presented with left-sided head tilt, dysphonia, head shaking,
inappetence and weight loss. A polypoid lesion had previously been removed from
the external ear canal. Otitis media with extension into the external ear canal
was suspected and investigated using video-otoscopy and computed tomography
examination. Invasive disease with extension from the middle ear to the base of
the skull, and intracranial extension into the caudal fossa and cranial cervical
vertebral canal was detected. Cytology of external ear canal exudate showed
capsulated budding yeasts and Cryptococcus gattii VGII was cultured. Treatment
with amphotericin B infusions and oral fluconazole was prescribed, with
nutritional support via oesophagostomy tube. The cat clinically recovered 12
months after treatment commenced. RELEVANCE AND NOVEL INFORMATION: This case
report describes the successful medical treatment of otogenic
meningoencephalomyelitis due to C gattii (VGII) infection in a cat.
PMID- 28491357
TI - Marked cytoreduction of a lymphocyte-rich mediastinal thymoma with neoadjuvant
chemotherapy in a cat.
AB - CASE SUMMARY: A 15-year-old neutered female domestic shorthair cat presented with
lethargy and acute-onset dyspnoea. Thoracic computed tomography (CT) revealed a
large, cranial mediastinal mass with an estimated volume of 180.7 cm3.
Chemotherapy consisting of dexamethasone followed by L-asparaginase,
prednisolone, vincristine and doxorubicin was commenced owing to the severity of
disease and initial possibility of lymphoma. A diagnosis of lymphocyte-rich
thymoma was made based upon histological examination, positive pancytokeratin
staining, variable lymphocyte CD3 expression and T cell receptor gamma
polyclonality. Thoracic CT performed 35 days after the commencement of
chemotherapy showed a marked reduction in the size of the mass, with an estimated
volume of 9.4 cm3. A median sternotomy and thymectomy were performed. No clinical
signs have recurred 34 months after surgery. CONCLUSIONS AND RELEVANCE: The
response to chemotherapy in this case was unusual, and is likely associated with
the high non-neoplastic lymphoid component of the mass. The case demonstrates
that preoperative chemotherapy can be used to reduce thymoma volume prior to
surgery, potentially decreasing anaesthetic risk.
PMID- 28491358
TI - Evaluation of thromboelastography in two factor XII-deficient cats.
AB - CASE SUMMARY: The current report describes thromboelastography (TEG) findings in
two cats with factor XII (FXII) deficiency. The first cat was diagnosed with
bilateral perinephric pseudocysts; hemostatic testing was performed prior to
performing renal aspirates. The second cat was healthy; hemostatic testing was
performed prior to inclusion into a research project. Both cats had markedly
prolonged partial thromboplastin times and hypocoagulable TEG tracings when
samples were activated with kaolin. However, when tissue factor (TF) was used to
activate the sample, both cats had normal-to-hypercoagulable TEG tracings. The
cats each had a subnormal FXII level. RELEVANCE AND NOVEL INFORMATION: TEG is
becoming widely used to investigate hemostasis in veterinary patients, and TEG
results in cats with FXII deficiency have not been previously reported. FXII
deficiency is the most common hereditary hemostatic defect in cats. While FXII
deficiency does not lead to in vivo hemorrhagic tendencies, it can lead to marked
prolongation in activated partial thromboplastin and activated clotting times,
and cannot be differentiated from true hemorrhagic diatheses without measuring
individual factor activity. With the increased use of TEG to evaluate hemostasis
in veterinary patients, it is important to recognize the effects of FXII
deficiency on this testing modality. The finding of a hypocoagulable kaolin
activated TEG tracing and a concurrent normal TF-activated TEG tracing in samples
should prompt clinicians to consider ruling out FXII deficiency.
PMID- 28491359
TI - Praziquantel treatment for Platynosomum species infection of a domestic cat on St
Kitts, West Indies.
AB - CASE SUMMARY: A 1-year-old, female spayed, domestic shorthair, indoor cat on the
island of St Kitts was diagnosed with platynosomiasis, infection with a feline
specific liver fluke, and treated with praziquantel at the marketed dose for
tapeworms (5 mg/kg; actual calculated dose 5.75 mg/kg). Serial fecal analyses
showed that egg counts decreased to zero within 10 days of treatment but re
emerged at day 17 and persisted at low levels until a second treatment was
administered on day 78. After the second treatment, all fecal samples (n = 15)
from day 85 to day 350 post-initial treatment were negative for Platynosomum ova.
RELEVANCE AND NOVEL INFORMATION: Treatment of platynosomiasis is poorly
documented; no drugs are labeled for use against Platynosomum and the efficacy of
suggested treatments is unknown. Using 5.75 mg/kg once, a dose that is
significantly lower than published recommended doses for platynosomiasis, egg
counts initially disappeared but re-emerged and persisted at low levels until a
second treatment was administered. We hypothesize that immature forms may not
have been killed and subsequently matured to produce eggs, or that the one-time
dose may not have been completely effective at eliminating all adult flukes.
However, administering praziquantel at 5.75 mg/kg twice, several weeks apart,
appeared to be effective in treating this cat with platynosomiasis, as evidenced
by monitoring of fecal egg counts over the course of 350 days.
PMID- 28491360
TI - Esophageal stricture caused by rib osteoma in a cat: case report.
AB - CASE SUMMARY: A 6-year-old male domestic shorthair cat presented with frequent
food regurgitation and dysphagia. Plain thoracic radiographs revealed a calcified
mass overlying the topography of the mediastinum, as well as dilation of the
cervical portion of the esophagus due to an accumulation of food. Endoscopic
examination showed a severe extraluminal esophageal stricture at the mediastinum
entrance. Surgery and a gastric tube were declined by the cat's owner, with
palliative support preferred. However, 1 year later, the cat presented with
severe cachexia, dysphagia, salivation, dehydration and inspiratory dyspnea.
Thoracic computed tomography was performed to evaluate the possibility of
surgical resection. A mass of bone density originating in the second left rib was
observed. The mass did not appear to have invaded adjacent structures but marked
compression of the mediastinal structures was observed. Surgical resection was
performed and a prosthetic mesh was used to reconstruct the thoracic wall.
Transient Horner's syndrome developed in the left eye postoperatively, and was
resolved within 4 weeks. Histopathology revealed a benign osteoma. Thirty-two
months after surgery, the cat was well and free of disease. RELEVANCE AND NOVEL
INFORMATION: Rib tumors should be included in a differential diagnosis in cats
with extraluminal esophageal stricture. CT should be performed for treatment
planning. Surgical treatment was curative in this case.
PMID- 28491361
TI - Orbital actinomycotic mycetoma caused by Streptomyces cinnamoneus.
AB - CASE SUMMARY: An 18-month-old male neutered Ragdoll cat presented with an 8 week
history of progressive unilateral right-sided mucopurulent nasal discharge and
exophthalmos. Magnetic resonance imaging revealed a heterogeneous right
retrobulbar mass and bilateral nasal cavity disease. Filamentous structures seen
on cytology of retrobulbar and nasal biopsies were mistakenly identified as
filamentous fungal hyphae. Subsequent investigations revealed that the cat had a
retrobulbar actinomycotic mycetoma with invasion of the globe. The aetiological
agent was identified on 16S recombinant DNA sequencing as Streptomyces
cinnamoneus. After exenteration and chronic antimicrobial therapy the cat was
alive and well 3 years after presentation. RELEVANCE AND NOVEL INFORMATION: This
is the first report of a pathogenic role of S cinnamoneus in a cat. Orbital
actinomycotic mycetomas in cats can resemble mycotic granulomas.
PMID- 28491362
TI - Successful conservative management of suspected Fournier's gangrene in cats:
three cases.
AB - CASE SERIES SUMMARY: Three cats with suspected Fournier's gangrene had an acute
onset of clinical signs and bloodwork changes consistent with sepsis. All cases
had similar progression of wounds that were managed without aggressive surgical
debridement, which is the currently accepted treatment of choice. All cats
survived and have maintained an excellent long-term quality of life. RELEVANCE
AND NOVEL INFORMATION: Fournier's gangrene is a potentially fatal disease, with
few cases reported in the veterinary literature. This retrospective case series
describes the only known reports of survival from suspected Fournier's gangrene
cats, none of which required aggressive surgical debridement.
PMID- 28491363
TI - Neuroendocrine pituitary macroadenoma of a cat presenting with primary adipsia
and hypernatraemia.
AB - CASE SUMMARY: A male neutered Ragdoll cat aged 11 years and 9 months presented
with a 6 month history of weight loss and a 1 month history of lethargy and
adipsia. A thorough clinical investigation confirmed a diagnosis of primary
adipsia and hypernatraemia secondary to a non-secretory neuroendocrine pituitary
macroadenoma. RELEVANCE AND NOVEL INFORMATION: Primary adipsia is a very rare
clinical entity. This report is the first to describe primary adipsia secondary
to a non-secretory pituitary macroadenoma in the cat. The veterinary literature
available in this field is very limited and this report adds a new differential
diagnosis for cats presenting with primary hypodipsia.
PMID- 28491364
TI - Traumatic spinal cord injury caused by suspected hyperflexion of the atlantoaxial
joint in a 10-year-old cat.
AB - CASE SUMMARY: A 10-year-old cat presented 5 days after a traumatic event with
acute recumbency followed by some clinical improvement. The neuroanatomical
localisation was the C1-C5 spinal cord segments. Initial survey radiographs,
including lateral flexed views, showed no convincing abnormalities. Magnetic
resonance imaging (MRI) revealed a marked focal intramedullary lesion at the
level of the dens and suspected oedema extending over C2-C3 vertebrae, suggesting
early syrinx formation. The cat made an initial excellent recovery on restricted
exercise without medical treatment. The MRI changes largely resolved on follow-up
MRI 4 weeks later yet recurred following a relapse 4 months later. At this stage,
a post-traumatic syrinx had developed. Moreover, the suspected atlantoaxial
instability was finally diagnosed on radiography with fully flexed lateral views.
A hyperflexion injury causing tearing of the atlantoaxial ligaments was
considered most likely given the lack of malformations or fractures. The cat made
a full recovery on conservative management. RELEVANCE AND NOVEL INFORMATION: This
is the first report of sequential MRI findings in a cat with atlantoaxial
instability. Moreover, post-traumatic syringomyelia formation following
atlantoaxial injury has not been reported. Sequential MRI aids in the diagnosis
of hyperflexion injury if survey radiographs fail to identify atlantoaxial
instability.
PMID- 28491365
TI - Ascending haemorrhagic myelomalacia associated with systemic hypertension in a
hyperthyroid cat.
AB - CASE SUMMARY: An 8-year-old domestic shorthair neutered male cat was presented
with acute onset of paraplegia, absent nociception on the pelvic limbs, tail and
perianal area, and a previous history of uncontrolled hyperthyroidism (even after
thyroidectomy) and chronic hypertension. The magnetic resonance findings
(heterogeneous intramedullary ill-defined area, isointense on T1-weighted and
hyperintense on short tau inversion recovery and T2-weighted scans between T12
and L5 spinal cord segments) were consistent with ascending haemorrhagic
myelomalacia, which was confirmed by histopathology. It also revealed
myelomalacia associated with diffuse arteriolar hyalinosis, similar to the
reports found with hypertensive encephalopathy. RELEVANCE AND NOVEL INFORMATION:
Myelomalacia should be considered as a possible outcome in cats with
hypertension. Considering that hypertension is a common consequence of
hyperthyroidism, emphasis should be given to blood pressure monitoring,
especially after treatment of this condition. We describe the histopathological
changes occurring in the spinal cord associated with a state of hypertension.
PMID- 28491366
TI - Migration of a sewing needle foreign body into the brainstem of a cat.
AB - CASE SUMMARY: A 1-year-old, female spayed domestic shorthair cat with a 6 week
history of upper respiratory signs and a progressive reluctance to move, which
culminated in a right-sided hemiparesis, was found to have a sewing needle
foreign body lodged in the brainstem. Surgical extraction of the needle was
successful and the cat's neurological deficits resolved over the days to weeks
following its removal. RELEVANCE AND NOVEL INFORMATION: This case report
describes, to our knowledge, the first reported incidence and management of an
ingested sewing needle migrating into the central nervous system of a cat.
PMID- 28491367
TI - Blepharitis due to Cryptococcus neoformans in a cat from northern Portugal.
AB - Case summary We report a clinical case of blepharitis due to Cryptococcus
neoformans yeasts in a 2-year-old stray cat from northern Portugal (Vila Real)
without concurrent naso-ocular signs. Ophthalmological examination revealed
mucopurulent discharge from an open wound in the right upper and lower lids. Slit
lamp biomicroscopy showed a normal anterior segment, and intraocular pressure was
within the normal reference interval. No fundoscopic alterations were detected in
either eye by direct and indirect ophthalmoscopic examination. Cytological
examination of an appositional smear showed numerous polymorphic neutrophils and
macrophages, together with spherical yeast cells compatible with Cryptococcus
species. Molecular analysis by means of PCR and restriction fragment length
polymorphism identified C neoformans genotype VNI. The cat was treated with
itraconazole, and amoxicillin and clavulanic acid, combined with a commercial ear
ointment and an imidacloprid/moxidectin spot-on application for bilateral
parasitic otitis caused by Otodectes cynotis. One month after treatment, the
clinical signs were completely resolved. Localised cutaneous lesions, as in the
present case, probably result from contamination of cat-scratch injuries with
viable encapsulated yeasts. Relevance and novel information This is, to the best
of our knowledge, the first clinical report of feline blepharitis due to C
neoformans without concurrent naso-ocular signs. The current findings, together
with those from recent reports of the infection in domestic animals, should alert
the veterinary community both in Portugal and in Europe to this underdiagnosed
disease.
PMID- 28491368
TI - First report of Cylicospirura felineus in a feral domestic shorthair cat in North
America.
AB - CASE SUMMARY: A feral domestic shorthair cat was euthanized owing to acute onset
and progression of neurological signs attributed to ethylene glycol toxicity. At
post-mortem examination two nodules were identified within the fundus of the
stomach. Examination of the gastric nodules revealed an intact mucosal surface,
each with multiple red slender nematodes extending through an individual central
pore. Histopathological evaluation of the nodules highlighted unique reactive
fibroplasia, mimicking feline gastrointestinal eosinophilic sclerosing
fibroplasia (FGESF), encasing numerous nematodes with females possessing gravid
uteri containing abundant larvated eggs. The latter findings were highly
suggestive of the Cylicospirura genus, further supported by an en face evaluation
of the buccal cavity, highlighting a distinctive trifid tooth appearance.
Together, these findings are consistent with Cylicospirura felineus. PCR for the
COX-1 gene was unsuccessful on formalin-fixed specimens, attributed to nucleic
acid and protein crosslinking. RELEVANCE AND NOVEL INFORMATION: This represents
the first documented case of Cylicospirura species in a feral domestic shorthair
cat in North America. This particular cat lived in the highly urban environment
of New Orleans, Louisiana. Identification of this case demonstrates the potential
for feral cats to serve as reservoir hosts and ultimately support transmission of
Cylicospirura species into domesticated cat populations. Gastric
cylicospiruriasis may present clinically as a firm abdominal mass, potentially
with a history of chronic vomiting. The latter emphasizes the importance of
differentiating this condition from a neoplastic process such as alimentary
lymphoma and adenocarcinoma. Histologically, the unique thick anastomosing
collagenous cords encasing nematodes represent a stereotypical response observed
in a broad array of gastrointestinal inflammation in felines, including
intralesional bacteria, fungal hyphae, foreign bodies and, in this case, gastric
nematodes that closely resemble FGESF. Additionally, these unique histological
lesions have previously been misinterpreted as neoplastic conditions, including
sclerosing mast cell tumor and extraosseous osteosarcoma.
PMID- 28491369
TI - Superficial temporal myofascial flap application in temporomandibular joint
arthroplasty in a cat.
AB - CASE SUMMARY: A 2-year-old, intact female domestic longhair cat was referred for
surgical treatment after diagnosis of closed jaw locking secondarily to right
temporomandibular joint ankylosis and left pseudoankylosis. The animal underwent
successful surgical management with bilateral excision arthroplasty followed by
interposition of a temporal superficial myofascial flap. Immediately after
surgery, the full range of lower jaw movement was achieved and normal occlusion
was maintained. Ankylosis did not recur in the 1 year postoperative follow-up
period. RELEVANCE AND NOVEL INFORMATION: A temporal myofascial flap could be
considered as interposition material after temporomandibular joint arthroplasty
to avoid postoperative re-ankylosis and mandibular drift. The main advantages of
this flap are its autogenous origin, and the ability to maintain separation
between the two bones, preserve mobility and disrupt new bone formation.
PMID- 28491370
TI - Primary angiocentric/angioinvasive T-cell lymphoma of the tympanic bulla in a
feline leukaemia virus-positive cat.
AB - Case summary A 5-year-old neutered female feline leukaemia virus (FeLV)-positive
domestic shorthair cat with a 5 month history of otitis media was referred for
head tilt, stertor and dyspnoea. Computed tomography scan revealed soft tissue
opacities inside the right tympanic bulla, with bone remodelling, and concurrent
nasopharyngeal and intracranial invasion. Endoscopically guided bioptic samples
were collected from the nasopharynx and middle ear. Histology revealed dense
sheets of round, large, neoplastic cells, often surrounding or invading vascular
walls. Neoplastic cells expressed CD3, FeLV p27 and gp70 antigens. A middle ear
angiocentric/angioinvasive T-cell lymphoma was diagnosed. After improvement of
clinical conditions following radiation therapy, the cat died unexpectedly. At
necropsy, hepatic and splenic spread was detected. Relevance and novel
information Primary middle ear tumours are rare and their diagnosis is often
delayed as clinical signs mimic more common otological conditions. Multiple
bioptic specimens are pivotal for a definitive diagnosis. The young age of the
cat, serology and immunohistochemistry revealed a possible transforming role of
FeLV.
PMID- 28491371
TI - Selective fatty replacement of the exocrine pancreas in a domestic shorthair cat:
histopathological findings with long-term outcome.
AB - The clinical, histopathological findings and eventual outcome of a cat with
marked and selective fatty replacement of the exocrine pancreas are described in
this case report. A 9-year-old female neutered domestic shorthair cat presenting
with polyphagia, weight loss and intermittent vomiting was diagnosed on
histopathology with severe exocrine pancreatic atrophy, with relative sparing of
the endocrine pancreas and replacement of the acinar cells by mature adipose
tissue. This case report discusses the histological findings in this case and the
eventual outcome, as well as the potential underlying causes of this histological
change.
PMID- 28491372
TI - Hypertrophic osteopathy in a cat with a concurrent injection-site sarcoma.
AB - Case summary An 11-year old neutered female domestic shorthair cat presented for
investigation of a large, partially ulcerated skin mass in the area of the left
scapula. The cat had been vaccinated 6 weeks previously in the same area.
Haematology showed a marked neutrophilia and monocytosis. Tru-cut biopsies were
taken and histopathology was consistent with a high-grade soft tissue sarcoma.
Thoracic radiographs and abdominal ultrasound revealed no abnormalities. Moderate
mixed (palisading, brush border and smooth) periosteal reaction was seen on the
diaphysis of long bones at the time of the radiographic examination. Magnetic
resonance imaging of the mass showed infiltration within deeper tissues and the
owners elected euthanasia. Post-mortem examination confirmed the presence of
hypertrophic osteopathy with a concurrent injection-site sarcoma. No evidence of
intra-thoracic or intra-abdominal disease was found. Relevance and novel
information To our knowledge, this is the first report where hypertrophic
osteopathy has been described in a cat with a soft tissue sarcoma, most likely an
injection-site sarcoma.
PMID- 28491373
TI - First case of feline leishmaniosis caused by Leishmania infantum genotype E in a
cat with a concurrent nasal squamous cell carcinoma.
AB - CASE SUMMARY: This is the first clinical report of feline viscerocutaneous
leishmaniosis caused by Leishmania infantum genotype E associated with an
invasive squamous cell carcinoma (SCC) in a domestic cat from Portugal.
Initially, the cat presented a single cutaneous lesion in the right nostril. A
fine-needle aspiration was performed and Leishmania amastigotes were observed
without the presence of cells compatible with neoplasia. Systemic treatment with
allopurinol was started. One year later, the cat presented a crateriform non
encapsulated and badly delineated mass in the nasal planum, with naso-oral
fistulation and nasal destruction. Histologically, the skin mass consisted on an
ulcerative plaque-like lesion with a nasal SCC. Leishmania infantum MON-1
parasites were detected by histopathology, culture and PCR of the skin mass,
submandibular and popliteal lymph nodes, liver and spleen. Restriction enzyme
analysis revealed genotype E, previously identified in humans and dogs living in
the same region. RELEVANCE AND NOVEL INFORMATION: This is, to the best of our
knowledge, the first clinical report of feline viscerocutaneous leishmaniosis
caused by L infantum genotype E. The detection and isolation of parasites from a
cat that are genetically identical to the ones obtained from humans and dogs with
visceral leishmaniosis highlights the need to clarify whether cats play a role in
the epidemiology of this parasitic zoonosis. From a clinical point of view, this
case reinforces the importance of including leishmaniosis in the differential
diagnoses of feline pathology, especially in cats with cutaneous lesions.
PMID- 28491374
TI - Supratentorial arachnoid cyst management by cystoperitoneal shunt in a 1-year-old
European cat.
AB - Arachnoid cysts are defined as an accumulation of fluid within the arachnoid
membrane. Feline intracranial arachnoid cysts are seldom reported, with only
three cases in the veterinary literature. A 1-year-old male neutered European cat
with a 24 h history of seizures was presented to the small animal neurology
department at Vetagro Sup, Lyon. Magnetic resonance imaging (MRI) revealed a
large intracranial arachnoid cyst ventral to the brain in the left temporal area.
Cystoperitoneal shunt placement resulted in complete resolution of the cyst
without recurrence (follow-up MRIs 3 weeks and 21 months after surgery).
Anticonvulsant treatment (phenobarbital 2.5 mg/kg q12h) was initiated at
presentation and gradually stopped after 17 months. Seizures recurred 4 months
after ending treatment, and seizure therapy was therefore restarted at the
initial dose. We report a case of an intracranial arachnoid cyst in an unusual
location not previously described. A cystoperitoneal shunt resolved the cyst
without complications. Maintenance anticonvulsant treatment was required to
control symptomatic epilepsy.
PMID- 28491375
TI - Incidental echocardiographic findings of a quadricuspid aortic valve associated
with aortic regurgitation in a cat.
AB - CASE SUMMARY: A 10-month-old male domestic shorthair cat was brought to
Kitanomori Animal Hospital for routine castration. Preoperative thoracic
radiography revealed a mildly enlarged heart silhouette, and transthoracic
echocardiography (ECHO) suggested a quadricuspid aortic valve associated with
central aortic regurgitation (regurgitant fraction 31%). After sedation with
intramuscular medetomidine and midazolam for castration, heart rate decreased
from 193 to 76 beats per minute. ECHO under sedation revealed two equally small
and two equally large aortic valve cusps, suggesting a type C quadricuspid aortic
valve. The findings were confirmed by real-time three-dimensional ECHO. RELEVANCE
AND NOVEL INFORMATION: This case reveals the echocardiographic features of a
feline quadricuspid aortic valve and shows that transthoracic ECHO is useful to
examine aortic valve morphology in cats. It also suggests that echocardiographic
screening may be beneficial for detecting congenital cardiac anomalies in
apparently healthy cats.
PMID- 28491376
TI - Digital flexor tendon contracture treated by tenectomy: different clinical
presentations in three cats.
AB - CASE SERIES SUMMARY: Three cats, Siamese or Siamese cross, were presented with a
chronic thoracic limb weightbearing lameness. Previous anti-inflammatory
administrations were unable to improve lameness consistently in the three cats.
Two of the three cats had undergone onychectomy several years before
presentation. A permanent flexion of the proximal interphalangeal joint of one or
more digits, associated with a difficult and painful extension of the proximal
interphalangeal joint, was noticed during orthopedic examination. A digital
flexor tendon contracture was suspected and confirmed with radiographic
examination. Surgical exploration was then performed. For all cats, treatment
consisted of a tenectomy or tenotomy of the superficial and deep digital flexor
tendons in order to release the contracture. The three cats responded well to the
surgical treatment and became sound around 2-4 weeks after surgery. RELEVANCE AND
NOVEL INFORMATION: Digital flexor tendon contracture is rarely reported as a
cause of lameness in cats. It should be considered in a differential diagnosis of
feline lameness whenever onychectomy has been performed in the past. The precise
etiology that explains this tendon contracture is unknown, but trauma or breed
predisposition could represent potential causes.
PMID- 28491377
TI - Cryptococcal nasopharyngeal polypoid mass in a cat.
AB - CASE SUMMARY: An indoor 9-year-old castrated male domestic cat was referred with
a 4 month history of increased upper airway noise. Computed tomography revealed a
nasopharyngeal polypoid mass, which was removed endoscopically with basket
forceps. Histopathology was compatible with a polypoid granulomatous pharyngitis
with Cryptococcus-like organisms. This was supported by a positive serum latex
cryptococcal antigen agglutination test (LCAT). Minimal inflammation of the nasal
tissue was noted on histopathology, with no evidence of fungus. Following
endoscopic removal of the mass, the patient was treated with systemic antifungal
medication (itraconazole). One year after diagnosis, the LCAT titer was negative
and the cat remained free of clinical signs. RELEVANCE AND NOVEL INFORMATION:
This case report emphasizes the importance of considering Cryptococcus species as
a potential etiology in cats presented with signs of nasopharyngeal obstruction
with an isolated nasopharyngeal polypoid mass, even if kept indoors.
PMID- 28491378
TI - Spontaneous thoracolumbar hematomyelia secondary to hemophilia B in a cat.
AB - CASE SUMMARY: A 10-year-old neutered male domestic shorthair cat presented for
evaluation of acute onset of paraplegia with loss of nociception and
thoracolumbar spine hyperesthesia and no history of trauma. Activated partial
thromboplastin time (aPTT) was markedly prolonged, and specific coagulation
factor testing revealed a factor IX level of 4% of normal activity, confirming
the presence of mild hemophilia B. Prior abnormal bleeding had occurred at the
time of castration as a kitten, as well as with laceration to a toe. Advanced
imaging, including computed tomography (CT) and magnetic resonance imaging (MRI)
of the thoracolumbar spine, confirmed the presence of multifocal intradural and
intramedullary spinal cord hemorrhage through demonstration of focal ring
enhancement on CT and multifocal areas of signal void on gradient echo T2* images
on MRI. Despite factor IX supplementation through the use of fresh frozen plasma
transfusions and normalization of the aPTT time, the cat's neurological status
did not improve. Owing to repeated urinary tract infections, with increasing
resistance to antibiotic therapy, the cat was ultimately euthanized. Post-mortem
examination showed no evidence of another underlying primary pathology for the
hematomyelia. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this case
demonstrates the first reported occurrence of spontaneous hematomyelia secondary
to hemophilia B in a cat.
PMID- 28491379
TI - Nasofacial infection in a cat due to a novel bacterium in Neisseriaceae.
AB - CASE SUMMARY: A 2-year-old female spayed domestic shorthair cat was presented for
a progressive subcutaneous nasofacial swelling. Histology of biopsy tissue
revealed pyogranulomatous inflammation and large numbers of gram-negative
capsulated bacterial coccobacilli within macrophages. The isolate was fastidious
and grew after 6 days under microaerophilic conditions in a candle jar. The
molecular identity of the isolate, from comparative sequence analysis of the 16s
rRNA gene, is an as yet to be classified bacterial species within a novel genus
of Neisseria. Infection resolved after 7 months of antimicrobial therapy with
doxycycline and trimethoprim sulfamethoxazole. There has been no further
recurrence of clinical signs in a 3 year follow-up period. RELEVANCE AND NOVEL
INFORMATION: Cats are susceptible to nasofacial infections as a result of
traumatic inoculation of environmental bacteria, fungi and protozoa. We report a
novel pathogen in the Neisseriaceae family, identified by 16 sRNA comparative
sequence analysis, as a cause of nasofacial infection in a cat, and its
subsequent successful treatment with combination antimicrobial therapy.
PMID- 28491380
TI - A survey of feline leukaemia virus antigenaemia among cats in eastern Austria: a
retrospective analysis of serum samples routinely tested between 1996 and 2011.
AB - OBJECTIVES: The aim of this retrospective analysis was to determine the
seroprevalence of feline leukaemia virus (FeLV) antigenaemia among owned cats in
Vienna and the surrounding area. METHODS: Samples were tested between 1996 and
2011 by the Department of Clinical Virology at the University of Veterinary
Medicine, Vienna, Austria. All samples were sent to the university as part of
routine diagnostic procedures, either to determine infection in clinically
symptomatic individuals or to rule out infection prior to vaccination. To allow
for statistical comparison, samples analysed between 2008 and 2011 were pooled
into one population (n = 444) and evaluated against samples tested in 1996 (n =
840). Furthermore, analyses of subgroups were undertaken to determine the effect
of sex and age on the prevalence of FeLV antigenaemia. RESULTS: With respect to
the samples tested at the University of Veterinary Medicine in Vienna, it was
determined that the level of FeLV antigenaemia in eastern Austria between 1996
and 2011 was 5.6%. The proportion of FeLV antigenaemic cats was highly variable
and has not fallen significantly over this period, despite advances in
vaccination, and the education of pet owners and animal welfare charities.
CONCLUSIONS AND RELEVANCE: This study confirms the importance of continued and
regular vaccination against FeLV among Austrian cats, particularly those allowed
access to the outdoors. Within the remit of this retrospective study, it was not
possible to follow-up results of repeat testing or of other assays (PCR) of
individual cats. As a result of this, no conclusions can be drawn as to the
possibility of transient antigenaemic cats or false-positive enzyme-linked
immunosorbent assay results.
PMID- 28491381
TI - A case of spongiform polioencephalomyelopathy in a cat with a history of
behavioural problems.
AB - A 7-month-old, entire female, domestic shorthair cat was referred to our
behavioural service owing to soiling in the house and a play-related problem. The
owners' complaints were that the cat had never used the litter tray, and it did
not know how to play. After reviewing the behavioural history, a problem of
substrate preferences acquisition was suspected with regard to the elimination
problem. During the consultation, the physical examination was unremarkable, but
the neurological examination revealed a moderate and hypermetric ataxic gait, and
a bilateral lack of menace response. Some degree of visual impairment was
suspected. The problem was located in the central nervous system (CNS);
specifically, an intracranial and multifocal problem was diagnosed. After a
complete work-up (complete ophthalmological examination, complete blood count and
a complete biochemistry panel, feline immunodeficiency virus/feline leukaemia
virus test, thorax radiographs, abdominal ultrasound, brain magnetic resonance
imaging [0.2 T], cerebrospinal fluid analysis and a urinary metabolic screen
test), a degenerative CNS problem was suspected. No treatment was prescribed for
the neurological problem. Regarding the problem of soiling in the house, reward
based training with a clicker was used, and the cat partially improved in a few
weeks. Three months later, the cat was referred to the neurology service in
status epilepticus. A symptomatic treatment was prescribed, with a mild response.
After 2 years of treatment and a progressive worsening, the cat was euthanased.
Necropsy revealed spongiform polioencephalomyelopathy. In order to rule out prion
aetiology a PrPsc inmunohistochemistry assay was performed, and the results were
negative. Congenital spongiform polioencephalomyelopathy (CSP) was diagnosed. We
strongly suggest that the cat's behavioural clinical signs were caused by the
CSP, causing learning impairment. To the best of our knowledge, this would be the
first case in which a congenital degenerative disease affected a cat's capability
to learn, leading to behavioural signs as the main complaint of the owners, even
before neurological signs are detected by the owners.
PMID- 28491382
TI - Bartonella henselae as a cause of acute-onset febrile illness in cats.
AB - CASE SERIES SUMMARY: At different time points spanning 6 months, three adopted
feral flea-infested cats, residing in the household of a veterinary technician,
became acutely anorexic, lethargic and febrile. Enrichment blood culture/PCR
using Bartonella alpha Proteobacteria growth medium (BAPGM) confirmed initial
infection with the same Bartonella henselae genotype in all three cases. With the
exception of anemia and neutropenia, complete blood counts, serum biochemical
profiles and urinalysis results were within reference intervals. Also, tests for
feline leukemia virus, feline immunodeficiency virus, Toxoplasma gondii and
feline coronavirus antibodies were negative. Serial daily temperature monitoring
in one case confirmed a cyclic, relapsing febrile temperature pattern during 1
month, with resolution during and after treatment with azithromycin. Bartonella
henselae Western immunoblot (WB) results did not consistently correlate with
BAPGM enrichment blood culture/PCR results or B henselae indirect fluorescent
antibody (IFA) titers, and WB titration results were not informative for
establishing antibiotic treatment failure. During the respective follow-up
periods, no illnesses or additional febrile episodes were reported, despite
repeat documentation of B henselae bacteremia in two cats available for follow-up
(one with the same genotype and the other with a different B henselae genotype);
one cat was, unfortunately, killed by dogs before follow-up testing. RELEVANCE
AND NOVEL INFORMATION: We conclude that microbiological diagnosis and treatment
of B henselae infection in cats can be challenging, that antibody titration
results and resolution of clinical abnormalities may not correlate with a
therapeutic cure, and that fever and potentially neutropenia should be
differential diagnostic considerations for young cats with suspected
bartonellosis.
PMID- 28491383
TI - Repair of a sliding (type I) hiatal hernia in a cat via herniorrhaphy,
esophagoplasty and floppy Nissen fundoplication.
AB - CASE SUMMARY: A 10-month-old domestic shorthair cat was evaluated for severe
esophagitis and protracted vomiting and regurgitation secondary to a sliding
(type I) hiatal hernia. The hernia and concurrent upper airway obstruction
(nasopharyngeal polyp) were diagnosed with a multi-modality approach, including
thoracic and abdominal radiographs, abdominal ultrasound, computed tomography and
endoscopy. Following unsuccessful attempts at medical management, lower
esophageal incompetence was successfully treated by employing a combination of
surgical techniques, including herniorrhaphy, esophagopexy and modified (floppy)
Nissen fundoplication. RELEVANCE AND NOVEL INFORMATION: A multi-modality imaging
approach was valuable in completely assessing the extent of this cat's disease.
Although an untraditional approach, the authors report herein the first clinical
description of the use of combined surgical techniques with the floppy Nissen
fundoplication technique (an antireflux procedure) in a cat. This procedure was
used as a first-line surgical technique in this cat with severe lower esophageal
incompetence, and may be a viable option for cases non-responsive to other
therapeutic interventions. Further investigation of this surgical technique is
warranted.
PMID- 28491384
TI - Bacterial pericarditis in a cat.
AB - CASE SUMMARY: A 4-year-old male neutered domestic shorthair cat was presented to
the Oregon State University cardiology service for suspected pericardial
effusion. Cardiac tamponade was documented and pericardiocentesis yielded
purulent fluid with cytologic results supportive of bacterial pericarditis. The
microbial population consisted of Pasteurella multocida, Actinomyces canis,
Fusobacterium and Bacteroides species. Conservative management was elected
consisting of intravenous antibiotic therapy with ampicillin sodium/sulbactam
sodium and metronidazole for 48 h followed by 4 weeks of oral antibiotics. Re
examination 3 months after the initial incident indicated no recurrence of
effusion and the cat remained free of clinical signs 2 years after presentation.
RELEVANCE AND NOVEL INFORMATION: Bacterial pericarditis is a rare cause of
pericardial effusion in cats. Growth of P multocida, A canis, Fusobacterium and
Bacteroides species has not previously been documented in feline septic
pericarditis. Conservative management with broad-spectrum antibiotics may be
considered when further diagnostic imaging or exploratory surgery to search for a
primary nidus of infection is not feasible or elected.
PMID- 28491385
TI - Chronic urinary bladder torsion causing urinary incontinence in a cat.
AB - CASE SUMMARY: A 10-month-old female spayed domestic shorthair cat was presented
for urinary incontinence. The cat was azotaemic, and ultrasound examination
identified hydroureter and hydronephrosis. Subsequent computed tomography (CT)
contrast pyelography allowed a diagnosis of urinary bladder torsion. Surgical
findings and treatment are described. Postoperatively, incontinence and azotaemia
resolved, and marked improvements were documented with ultrasound and CT in
urinary tract structural abnormalities. RELEVANCE AND NOVEL INFORMATION: To our
knowledge, urinary bladder torsion has not been previously reported in the cat.
This case most probably occurred as a complication of ovariohysterectomy, as has
been reported in the dog; however, the presenting sign of chronic urinary
incontinence is unique. Response to surgical correction was favourable.
PMID- 28491386
TI - Proliferative, necrotizing and crescentic immune complex-mediated
glomerulonephritis in a cat.
AB - CASE SUMMARY: A 5-year-old cat was examined for vomiting and anorexia of 2 days'
duration. Azotemia, hyperphosphatemia and hypoalbuminemia were the main
biochemical findings. Serial analyses of the urine revealed isosthenuria,
proteinuria and eventual glucosuria. Hyperechoic perirenal fat was detected
surrounding the right kidney by ultrasonography. Histopathologic evaluation of
ante-mortem ultrasound-guided needle biopsies of the right kidney was consistent
with proliferative, necrotizing and crescentic glomerulonephritis with fibrin
thrombi, proteinaceous and red blood cell casts, and moderate multifocal chronic
active interstitial nephritis. Owing to a lack of clinical improvement, the cat
was eventually euthanized. Post-mortem renal biopsies were processed for light
microscopy, transmission electron microscopy and immunofluorescence. This
revealed severe focal proliferative and necrotizing glomerulonephritis with
cellular crescent formation, podocyte injury and secondary segmental sclerosis.
Ultrastructural analysis revealed scattered electron-dense deposits in the
mesangium, and immunofluorescence demonstrated positive granular staining for
lambda light chains, consistent with immune complex-mediated glomerulonephritis.
Severe diffuse acute tubular epithelial injury and numerous red blood cell casts
were also seen. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the
first report of naturally occurring proliferative, necrotizing and crescentic
immune complex glomerulonephritis in a cat.
PMID- 28491387
TI - Lumbosacral intraspinal extradural ganglion cyst in a cat.
AB - CASE SUMMARY: A 16-year-old neutered female domestic shorthair cat was referred
for chronic history of reluctance to jump, stiffness of the tail and lower back
pain. Mild pelvic limb ataxia, reduced perianal reflex and lumbosacral discomfort
were present on neurological examination. On magnetic resonance imaging, a well
defined rounded structure of 3 mm in diameter was identified on the right dorsal
aspect of the epidural space at L7-S1, causing displacement of the cauda equina.
The lesion was hyperintense to spinal cord parenchyma on T2-weighted images and
hypointense on T1-weighted images, consistent with a fluid-filled structure. A
Lumbosacral dorsal laminectomy was performed. A clear fluid-containing structure
was identified between the right L7 nerve root and the cauda equina. Following
surgical excision, histopathology confirmed the cystic nature of the lesion and
revealed thick disorganised sheaths of fibrocollagenous tissue and flattened
mesenchymal cells lining the luminal part of the cyst wall. A diagnosis of
intraspinal ganglion cyst was made. The cat recovered uneventfully. Seven months
after surgery euthanasia was performed for unrelated reasons; no neurological
deficits were present. RELEVANCE AND NOVEL INFORMATION: This is the first
reported case of intraspinal ganglion cyst in a cat. Intraspinal extradural cysts
should be considered among other differential diagnoses for cats with lumbosacral
myelopathy/radiculopathy.
PMID- 28491388
TI - Osteitis fibrosa cystica in a domestic young cat.
AB - CASE SUMMARY: A 4-month-old cat had bilateral swellings of the mandible, maxilla,
humerus and femur, and angular deviations in the axial and appendicular skeleton.
The biochemical profile indicated hypercalcemia, hyperphosphatemia and increased
parathyroid hormone levels. Because of the poor prognosis, the cat was
euthanized. At necropsy, malleable and fragile bones, associated with numerous
cystic areas containing yellowish and translucent liquid, were observed.
Histologically, the bones showed marked diffuse proliferation of fibrous
connective tissue, and large numbers of osteoclasts surrounding numerous cystic
structures were also observed within fibrotic areas at the periphery of the
trabecular bone. In addition, enlargement of the parathyroid glands, which was
associated with increased serum concentrations of calcium, phosphorus and
parathyroid hormone, was detected. RELEVANCE AND NOVEL INFORMATION: The changes
observed in this cat are consistent with hyperparathyroidism-associated osteitis
fibrosa cystica, which is an unusual presentation in the cat.
Hyperparathyroidism, either primary (neoplastic) or secondary (nutritional or
renal), is the primary cause of this condition.
PMID- 28491389
TI - Paraneoplastic neutrophilic leukocytosis syndrome in a cat with recurrent mammary
carcinoma.
AB - CASE SUMMARY: A spayed 12-year-old female domestic shorthair cat presented with
nodular lesions on the ventral-right thoracic wall after complete mastectomy 4
months previously. The prior diagnosis was tubulopapillary mammary carcinoma with
axillary lymph node metastasis, and a recurrence was confirmed. A gradual and
sequential increase in the total number of leukocytes with severe neutrophilia
(95.632/ul) developed over the course of the illness, along with an increase in
the size of the recurrent mass. The severe leukocytosis did not show any response
to antibiotic therapy, and no evidence of infection was observed. Bone marrow
cytology confirmed hypercellularity in the myeloid cell lineage. Based on these
findings, paraneoplastic neutrophilic leukocytosis syndrome was suspected. An
incisional biopsy of the recurrent mass was consistent with recurrent
tubulopapillary mammary carcinoma. Malignant epithelial cells stained positive
upon immunohistochemistry for granulocyte-macrophage colony-stimulating factor,
cytokeratin and vimentin. After the final diagnosis of paraneoplastic
neutrophilic leukocytosis syndrome, the cat was euthanized at the owner's
request. RELEVANCE AND NOVEL INFORMATION: This is a novel case of paraneoplastic
leukocytosis syndrome associated with mammary carcinoma in a cat. Although there
are some reports describing paraneoplastic leukocytosis in cats, the relationship
between this syndrome and feline mammary tumors has not been described.
PMID- 28491390
TI - Extrahepatic biliary duct obstruction as a result of involuntary transcavitary
implantation of hair in a cat.
AB - CASE SUMMARY: A 4-year-old male neutered domestic shorthair cat was referred for
investigation of jaundice. The cat had a recent history of a skin laceration
repair following trauma. Sequential serum biochemistry demonstrated increasing
plasma bilirubin concentrations; abdominal ultrasonography revealed ongoing
pancreatitis and apparent extrahepatic obstruction of the common bile duct.
Exploratory laparotomy identified constriction of the common bile duct with
foreign material (cat hair). The constricting band of hair was removed
surgically; cholecystoduodenostomy was performed. Postsurgical quality of life is
excellent with chronic treatment of tylosin, omeprazole and ursodeoxycholic acid.
RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the first reported
case of extrahepatic biliary duct obstruction resulting from the intra-abdominal
migration of a foreign body, in this case, hair shafts. The mechanism by which
this occurred was likely a combination of physical constriction by the hair
shafts and subsequent foreign body reaction surrounding this. This should be
included in the differential diagnosis of a cat with jaundice.
PMID- 28491391
TI - Effect of age and surgical approach on perioperative wound complication following
ovariohysterectomy in shelter-housed cats in Australia.
AB - OBJECTIVES: The aim of the study was to investigate the effects of age and/or
surgical approach on perioperative wound complication following
ovariohysterectomy (OHE). METHODS: A retrospective search of perioperative
monitoring records from a shelter desexing program was conducted to identify cats
that underwent OHE between 1 June 2010 and 31 December 2012 inclusive. A wound
complication was defined as gross observation of inflammation or wound dehiscence
at the surgical site in the 5 day postoperative period. Cases were grouped
according to age (<=12 weeks or >12 weeks) and surgical approach (flank or
midline). Stratified analyses were conducted to evaluate the association between
surgical approach and wound complications, after adjusting for age. Mantel
Haenszel adjusted risk ratio, Cochran-Mantel-Haenszel test statistic and their
95% confidence intervals were presented. RESULTS: A total of 312 cases met the
study criteria. The overall wound complication risk was low (6.09%) and was not
related to age. A midline approach was associated with a 4.59-times increased
risk of wound complication, compared with a flank approach in cats up to 12 weeks
of age (P = 0.015) but not in older cats. CONCLUSIONS AND RELEVANCE: These
findings support the practice of prepubertal desexing for cats.
PMID- 28491392
TI - Glenoidectomy for treatment of a comminuted scapular fracture in a cat.
AB - CASE SUMMARY: This case report describes the surgical technique used and clinical
outcome of a 15-year-old neutered female cat that had a comminuted fracture of
the right glenoid and scapular neck secondary to a gunshot injury that was
treated with glenoidectomy. RELEVANCE AND NOVEL INFORMATION: Good clinical
outcomes are possible with removal of the glenoid for treatment of comminuted
fractures of the scapulohumeral joint. Glenoidectomy is a viable alternative to
amputation in cats with normal neurovascular supply to the affected limb.
Persistent functional, pain-free lameness, muscle hypertrophy and changes in
shoulder range of motion are to be expected.
PMID- 28491393
TI - Persistent right aortic arch with an aberrant left subclavian artery, Kommerell's
diverticulum and bicarotid trunk in a 3-year-old cat.
AB - CASE SUMMARY: A 3-year-old male, neutered, domestic shorthair cat with a history
of chronic regurgitation since being obtained as a kitten was presented for
weight loss and regurgitation of all ingested food. The cat was in poor body
condition and had a firm swelling in the ventral neck at the time of
presentation. Thoracic radiographs showed severe dilation of the entire cervical
and cranial intrathoracic esophagus to the level of the heart base. Computed
tomographic angiography (CTA) showed a persistent right aortic arch with an
aberrant left subclavian artery and severe dilation of the cervical and
intrathoracic esophagus cranial to the heart base. CTA also showed a bicarotid
trunk and Kommerell's diverticulum to be present, which are rare vascular
structures in the cat. Esophagoscopy showed esophageal dilation and multiple
compact trichobezoars obstructing the esophagus. Removal of the obstructing
trichobezoars resulted in resolution of clinical signs, and the cat was able to
drink water and eat a canned food slurry without regurgitation. Surgical
correction was not pursued. RELEVANCE AND NOVEL INFORMATION: Vascular ring
anomaly (VRA) should be considered in all cats with a history of regurgitation,
regardless of their age at the time of presentation. CTA is a valuable diagnostic
imaging procedure that allows differentiation of a VRA from other causes of
esophageal obstruction and provides information about the VRA that can be used to
determine amenability to surgical correction.
PMID- 28491394
TI - Primary goitrous hypothyroidism in a young adult domestic longhair cat: diagnosis
and treatment monitoring.
AB - CASE SUMMARY: Primary goitrous hypothyroidism was diagnosed in a 12-month-old cat
examined because of small stature, mental dullness, severe lethargy, generalized
weakness and gait abnormalities. Radiographs of the long bones and spine revealed
delayed epiphyseal ossification and epiphyseal dysgenesis. Diagnosis of primary
hypothyroidism was confirmed by low serum concentrations of total and free
thyroxine (T4) with high thyroid-stimulating hormone (TSH) concentrations.
Thyroid scintigraphy revealed severe enlargement of both thyroid lobes, as
evidenced by a seven-fold increase in calculated thyroid volume above the
reference interval. In addition, this bilateral goiter had an extremely high
radionuclide uptake, about 10-fold higher than the normal feline thyroid gland.
Treatment with twice-daily levothyroxine (L-T4), administered on an empty
stomach, resulted in increased alertness, playfulness, strength and improvement
in gait, as well as an increase in body length and weight. L-T4 replacement also
led to normalization of serum thyroid hormone and TSH concentrations, and
complete resolution of goiter. RELEVANCE AND NOVEL INFORMATION: Spontaneous
hypothyroidism is rarely reported in cats, with congenital hypothyroidism in
kittens diagnosed most frequently. Despite the fact that this cat was a young
adult, it likely had a form of congenital hypothyroidism caused by
dyshormonogenesis (defect in thyroid hormone synthesis) that led to compensatory
development of goiter. In hypothyroid cats, treatment with L-T4 is best given
twice daily on an empty stomach to ensure adequate absorption. Normalization of
serum TSH and shrinkage of goiter, as well as improvement in clinical signs, is
the goal of treatment for cats with goitrous hypothyroidism.
PMID- 28491395
TI - Probable primary polydipsia in a domestic shorthair cat.
AB - CASE SUMMARY: A 10-month-old neutered male domestic shorthair cat presented with
a 4 month history of polyuria and polydipsia. After a thorough diagnostic work-up
the only abnormal findings were hyposthenuria and an elevated random plasma
osmolality level. Trial therapy with the oral and ophthalmic forms of
desmopressin failed to concentrate urine. A modified water deprivation test
confirmed the ability to concentrate urine above a urine specific gravity (USG)
of 1.035. After transitioning the cat to a higher sodium diet and instituting
several enrichment changes to the cat's environment, average water consumption
and urine output levels decreased to almost normal levels and USG increased from
1.006 to 1.022. These findings provide strong evidence that primary polydipsia
was the underlying etiology of the cat's condition. RELEVANCE AND NOVEL
INFORMATION: This case report exemplifies the challenges faced when a cat
presents for polyuria and polydipsia without an obvious cause identified on
routine diagnostics. To our knowledge, this is the first report of primary
polydipsia in a cat.
PMID- 28491396
TI - Tetrathyridiosis in a domestic shorthair cat.
AB - CASE SUMMARY: This report describes the clinical and parasitological findings in
a domestic shorthair cat with isolated thoracic tetrathyridiosis. The cat was a
stray from Malta that had lived in Germany for several years since as an indoor
only cat. Therefore, the process of infection remains very unusual. In this case
it must be considered that the cat had been infected years previously while in
Malta, and had lived at least 4 years without any clinical signs. It was possible
to diagnose this uncommon disease and initiate an effective treatment with
fenbendazole, praziquantel and supportive care. Clinical signs, as well as
radiographic findings, were regressive with this treatment. RELEVANCE AND NOVEL
INFORMATION: Tetrathyridiosis is a rare finding in cats, especially in Germany,
but it seems to be a potential differential diagnosis of pleural effusion.
Mesocestoides corti, which was the causative parasite in this case, has not
previously been isolated in Germany. Because tetrathyridiosis is only diagnosed
post mortem in most cases, little is known about effective therapeutic options.
Furthermore, clinical signs of this disease can be absent for several years and
can potentially be triggered by neoplastic conditions or immunosuppression.
Tetrathyridiosis seems to be a treatable disease that can be controlled by
adequate antiparasitic therapy.
PMID- 28491397
TI - Successful subtotal orbitectomy in a cat with osteoma.
AB - CASE SUMMARY: A 14-year-old Siamese neutered male cat was evaluated for anorexia
and a left periorbital mass. Skull radiographic findings showed a well-defined
lesion resembling new compact bone formation without destruction. A subtotal
orbitectomy was indicated. The tumor was removed intact with a normal tissue
margin of at least 1 cm. There were no postsurgical complications.
Histopathologic examination revealed an osteoma. The cat returned to normal
appetite and activity 15 days after surgery. Six months after surgery, there were
no gross signs of recurrence. RELEVANCE AND NOVEL INFORMATION: Periorbital tumors
are infrequently diagnosed in companion animals and most are malignant. In this
case, the diagnosis was orbital osteoma. The most commonly affected bone for
osteoma in cats is the mandibular bone; few cases have been identified in orbital
bones. Orbital surgery has the potential to be challenging owing to complex
anatomy, difficult exposure and the tendency to bleed. Surgical complications are
common. In this case, although the disease was advanced, subtotal orbitectomy was
successfully performed.
PMID- 28491398
TI - Adrenocortical tumor in a cat secreting more than one type of corticosteroid.
AB - CASE SUMMARY: A 14-year-old, spayed female domestic shorthair cat was evaluated
because of a right adrenal mass. The referring veterinarian had started treatment
for hypokalemia and systemic arterial hypertension. During the initial evaluation
the cat was alert and responsive, and serum potassium concentration was within
the reference range. Serum concentrations of aldosterone and progesterone were
increased. Atrophy of the contralateral adrenal and an exaggerated response of
cortisol to stimulation with adrenocorticotropic hormone suggested hypersecretion
of cortisol. Unilateral adrenalectomy was performed and recovery was uneventful.
Histologic examination of the mass revealed an adrenocortical tumor. After
surgery, clinical signs of hypercortisolism, hyperaldosteronism and
hyperprogesteronism were no longer observed, and neither potassium
supplementation nor antihypertensive treatment were needed. RELEVANCE AND NOVEL
INFORMATION: In cases with an adrenocortical tumor, clinicians should investigate
whether the tumor hypersecretes glucocorticoids, mineralocorticoids, sex steroids
or combinations of these. Hypersecretion of more than one adrenal hormone may
occur in a cat with an adrenocortical tumor.
PMID- 28491399
TI - Antigenemia without antigenuria in a cat with histoplasmosis.
AB - CASE SUMMARY: Based on demonstration of the yeast phase of Histoplasma capsulatum
on fine-needle aspirate cytology of the kidney, a 5-year-old cat was diagnosed
with histoplasmosis. Urine and serum were tested for antigen via a Histoplasma
antigen enzyme immunoassay. At the time of diagnosis, and on multiple occasions
during antifungal treatment, antigenemia was detected without antigenuria. The
cat was treated with standard therapy and achieved clinical remission. RELEVANCE
AND NOVEL INFORMATION: Diagnosis is most commonly made by finding the yeast phase
of H capsulatum via cytology of fluid samples or cytology or histopathology of
infected tissues. In certain cases this may require invasive tests. Recently, a
non-invasive test, a Histoplasma antigen enzyme immunoassay, has been shown to be
a sensitive test for supporting the diagnosis of histoplasmosis in cats. Urine
has been considered the biologic specimen of choice for antigen testing and there
is a paucity of information concerning the use of other specimens such as serum.
The case herein reports a cat with antigenemia without antigenuria. These
findings suggest that further research is necessary to better understand the
ideal biologic sample or combination of samples as it pertains to antigen testing
in cats. It also suggests that to maximize sensitivity both urine and serum may
need to be tested in cats with suspected histoplasmosis.
PMID- 28491400
TI - Congenital hepatic fibrosis and polycystic kidney disease not linked to C >A
mutation in exon 29 of PKD1 in a Persian cat.
AB - CASE SUMMARY: We describe the case of a 1-year-old male Persian cat diagnosed
with congenital hepatic fibrosis (CHF) associated with renal polycystic disease
and, for the first time, we have shown that there was no C >A mutation in exon 29
of PKD1 (polycystic kidney disease 1). The cat presented with a history of
chronic weight loss, anorexia, vomiting, depression and lethargy, with profuse
salivation and ascites on clinical examination. A mild elevation in liver
associated plasma enzymes suggested a hepatic disease. Owing to the cat's
deteriorating condition, it was euthanized. During necropsy, the liver was found
to be enlarged, firm and reddish, and the kidney had multiple small cortical
cysts. Immunohistochemistry revealed that bile duct cells and epithelial cells of
renal cysts showed positive immunoreactivity to keratin 19. Collagen fibers
surrounding bile ducts within portal areas demonstrated reactivity to type IV
collagen antibody, confirming the congenital nature of the process. A diagnosis
of ductal plate malformation consistent with CHF associated with polycystic
kidney in a young Persian cat was made. Interestingly, genetic testing revealed a
wild-type sequence at position 3284 in exon 29 of PKD1. RELEVANCE AND NOVEL
INFORMATION: The absence of the classic genetic mutation associated with the
particular clinical presentation supports the hypothesis of a distinct
etiopathogenesis among fibropolycystic diseases in domestic cats. Moreover,
congenital hepatic fibrosis is a rare but important differential diagnosis for
young Persian cats and their crosses with clinical signs of chronic end-stage
liver disease.
PMID- 28491401
TI - Nosocomial feline calicivirus-associated virulent systemic disease in a
veterinary emergency and critical care unit in France.
AB - CASE SERIES SUMMARY: In October 2011, an abnormally large morbidity and mortality
event was noted in the intensive care unit (ICU) of a veterinary school hospital
in Nantes, France. Cats, and cats only, transferred from the emergency room
presented with fever, ulcers on the tongue and cutaneous lesions around
venepuncture or surgical incision sites, leading to suspicion of a feline
calicivirus-associated virulent systemic disease confirmed with reverse
transcriptase-polymerase chain reaction. A total of 14 cats were suspected. The
clinical features and the origin of the contamination were described for each
cat. The median length of incubation was 4.5 days. Fifty-seven percent of the
cats were euthanased (8/14) and 21% died (3/14), with a combined mortality of 79%
(11/14) - the highest ever reported. Median survival was 12 days. The recovery
rate was 21% (3/14). RELEVANCE AND NOVEL INFORMATION: Eight outbreaks have been
reported, in veterinary clinics or in group-housed cats. The main unusual aspects
of the present outbreak were: (1) the extreme flare-up of lesions at sites of
skin breach, precluding any puncture/incision; (2) the suggested better survival
rate at home than in hospital; and (3) the immediate control of the outbreak
after recognition of the disease. Other striking but less unusual features of
this outbreak were: (4) the increasing of the virulence of the calicivirus with
the passage of time; and (5) the primary role that the caregivers' hands played
in the spread of the outbreak.
PMID- 28491402
TI - Feline paraneoplastic alopecia associated with metastasising intestinal
carcinoma.
AB - CASE SUMMARY: A 10-year-old male neutered British Shorthair cat was presented
with a 6 month history of lethargy, weight loss and alopecia. Clinical
examination revealed widespread alopecia of the ventral abdomen and hindlimbs.
The skin in these areas was smooth and shiny and hairs could be easily epilated.
Spontaneous pruritus was observed. Cytological examination of superficial
impression smears showed a severe Malassezia species dermatitis and pyoderma.
Ectoparasites could not be detected and no sign of dermatophytosis was visible in
trichograms and Wood's lamp analysis. Abdominal ultrasound found a focally
thickened wall of the large intestine and multiple nodules in the liver. Fine
needle aspirates from lymph nodes, liver and altered colonic wall were consistent
with an undifferentiated malignant neoplasia. The cat was euthanased at the
owners' request, owing to potential neoplasia with metastatic spread. At necropsy
a metastasising carcinoma of the colonic wall was found, as well as a
paraneoplastic alopecia. RELEVANCE AND NOVEL INFORMATION: Feline paraneoplastic
alopecia has been reported in association with pancreatic carcinoma, bile duct
carcinoma and hepatocellular carcinoma, as well as with neuroendocrine pancreatic
carcinoma and hepatosplenic plasma cell tumour. This is the first reported case
of feline paraneoplastic alopecia associated with a colon carcinoma.
PMID- 28491403
TI - Trichomonosis in cats with diarrhoea in Hong Kong, China, between 2009 and 2014.
AB - CASE SERIES SUMMARY: Infection of the domestic cat by Tritrichomonas blagburni,
previously referred to as T foetus, may lead to a disease called feline
trichomonosis, which manifests clinically as large bowel diarrhoea. The disease
has a wide geographical distribution, including numerous countries in Europe,
North America and Australia/Oceania. Nevertheless, it has occasionally been
reported in Asia, South Korea and Japan. A retrospective study was carried out to
include all domestic cats with diarrhoea, presented to two veterinary clinics in
Hong Kong, China, between 1 July 2009 and 30 June 2014. A total of 29 cats with
diarrhoea were diagnosed with Tritrichomonas species infection by means of
quantitative PCR and direct microscopy. Tritrichomonas species was more
frequently found in young (median age 10 months), male (66%) and purebred cats
(86%). Giardia species was found in 31% of Tritrichomonas species-positive cats.
The recommended dose of ronidazole (30 mg/kg q24h for 14 days) resolved clinical
signs in 83% of diagnosed cats. RELEVANCE AND NOVEL INFORMATION: This case series
describes Tritrichomonas species as a cause for feline chronic diarrhoea in cats
in China. The high rate of failure (17%) in those cats receiving a standard
regimen of ronidazole might be due to owner or patient compliance rather than
protozoal resistance to the drug.
PMID- 28491404
TI - Surgical resolution of an oesophageal duplication cyst causing regurgitation in a
domestic shorthair cat.
AB - CASE SUMMARY: An 18-month-old female domestic shorthair cat was referred for
investigation of a 6 month period of regurgitation. Contrast radiography
indicated an intramural oesophageal structure. Ultrasound-guided fine-needle
aspiration of the area retrieved viscous fluid containing high numbers of
squamous epithelial cells. Computed tomography disclosed a thin-walled contrast
enhancing structure containing non-enhancing homogenous contents. Exploratory
thoracotomy confirmed an intramural cystic oesophageal structure, which was
resected. Histopathological analysis of the resected tissue demonstrated an
intramural oesophageal duplication cyst. A 12 month follow-up period has seen
complete resolution of the cat's clinical signs. RELEVANCE AND NOVEL INFORMATION:
This is the first report of successful oesophageal duplication cyst removal in a
cat. Oesophageal duplication cysts should be included on the differential list
for dysphagia and regurgitation in cats. Complete surgical removal in this cat
carried a good long-term outcome.
PMID- 28491405
TI - Aldosterone and progesterone-secreting adrenocortical adenocarcinoma in a cat
with a concurrent meningioma.
AB - CASE SUMMARY: A 12-year-old, male neutered domestic shorthair cat was referred
for investigation of suspected hyperaldosteronism due to persistent hypokalaemia,
hindlimb ataxia, weakness of 1 month's duration and a left adrenal mass that was
detected on abdominal ultrasound. Neurological examination findings at referral
were suggestive of a concurrent left forebrain lesion. Hyperaldosteronism and
concurrent hyperprogesteronism were confirmed on endocrine testing. On computed
tomography (CT) of the abdomen and thorax there was no evidence of local vascular
invasion by the adrenal mass or of metastatic disease. CT and magnetic resonance
imaging featured a large, focal rim-enhancing extra-axial left forebrain lesion
consistent with a meningioma. Surgical excision of the forebrain mass was
followed by adrenalectomy 2 weeks later. The tumours were classified on
histopathology as a psammomatous meningioma and an adrenocortical adenocarcinoma,
respectively. Immunohistochemical staining of the meningioma confirmed the
presence of progesterone receptors. The cat remains well 2 years later. RELEVANCE
AND NOVEL INFORMATION: In humans, elevated serum progesterone levels have been
associated with rapid growth of meningiomas due to the presence of progesterone
receptors on the tumour. This is the first report of a cat with a progesterone
and aldosterone-secreting adrenocortical adenocarcinoma and a concurrent
meningioma. Clinicians should be aware of the potential effect of elevated
progesterone on meningiomas in cats.
PMID- 28491406
TI - Cutaneous squamous cell carcinoma manifesting as follicular isthmus cysts in a
cat.
AB - CASE SUMMARY: A 9-year-old spayed female domestic shorthair cat was examined for
swelling of the right upper lip. The cat had been receiving oral ciclosporin A
for eosinophilic plaques. The swelling appeared clinically and cytologically
consistent with an abscess; exudate was cultured and treatment consisted of
antibiotic therapy and surgical curettage. Five months of antibiotic therapy with
three separate surgical treatments resulted in minimal improvement; three
separate biopsy samples demonstrated epithelial cysts with severe dermal
inflammation. Swelling and drainage of purulent material from the affected lip
persisted and progressed to involve the left upper lip. Euthanasia was elected 13
months after initial examination due to disease progression. On necropsy,
histopathology demonstrated multiple isthmus cysts intermixed with squamous cell
carcinoma (SCC). RELEVANCE AND NOVEL INFORMATION: The clinical and
histopathologic features were unusual for feline cutaneous SCC. The cystic nature
and lack of epidermal involvement suggest the tumor arose from non-epidermal
squamous cells such as follicular isthmus or ductal epithelium. There is a
pattern of SCC recognized in human renal transplant patients with features of
epidermal inclusion cysts. These features have not been previously reported in
SCC from a cat.
PMID- 28491407
TI - Uterine prolapse with endometrial eversion in association with an unusual
diffuse, polypoid, fibrosing perimetritis and parametritis in a cat.
AB - CASE SUMMARY: This case describes a young non-pregnant cat that presented with
uterine prolapse in association with an unusual diffuse, polypoid, fibrosing
perimetritis and parametritis. Following ovariohysterectomy the cat recovered
fully. No intra-abdominal complications were seen on ultrasound examination 3
months postsurgery. At the time of writing, the cat remains healthy. RELEVANCE
AND NOVEL INFORMATION: Uterine prolapse in the cat is relatively rare and usually
associated with the periparturient period. Inflammatory polypoid perimetritis and
parametritis have not previously been documented in cats, and in dogs have only
been reported in association with the administration of oestrogenic compounds.
The polypoid inflammation affecting the uterus and parametrium may have
contributed to increased laxity of the uterine ligaments and predisposed to the
development of uterine prolapse.
PMID- 28491408
TI - Benign cementoblastoma (true cementoma) in a cat.
AB - CASE SUMMARY: A 10-year-old castrated male domestic shorthair cat was presented
for assessment of a gingival mass surrounding the left maxillary third and fourth
premolar teeth. The mass was surgically removed by means of a marginal rim
excision, and the tissue was submitted for histological assessment. It was
identified as a benign cementoblastoma (true cementoma). There was proliferation
of mineralized eosinophilic material with multiple irregularly placed lacunae and
reversal lines, reminiscent of cementum. The cat recovered uneventfully from the
anesthesia, and there was no evidence of tumor recurrence 6 months after surgery.
RELEVANCE AND NOVEL INFORMATION: Cementoblastomas (true cementomas) in domestic
animals are rare, with just a few reports in ruminants, monogastric herbivores
and rodents. Cementoblastoma is considered a benign tumor that arises from the
tooth root. The slow, expansive and constant growth that characterizes these
masses may be accompanied by signs of oral discomfort and dysphagia. This case
report is intended to increase knowledge regarding this tumor in cats and also
highlights the importance of complete excision of the neoplasm. To our knowledge,
there are no previous reports in the literature of cementoblastoma in the cat.
PMID- 28491409
TI - The first volume of JFMS Open Reports.
PMID- 28491410
TI - Lumbosacral agenesis in a cat.
AB - CASE SUMMARY: Lumbosacral agenesis is a rare congenital condition reported in
children. We report a 17-week-old female domestic shorthair cat with lumbosacral
agenesis on whole-body radiographs. The cat was euthanized shortly thereafter
presentation. A necropsy was not permitted. RELEVANCE AND NOVEL INFORMATION: This
is the first reported feline case of lumbosacral agenesis.
PMID- 28491411
TI - Successful treatment of feline leishmaniosis using a combination of allopurinol
and N-methyl-glucamine antimoniate.
AB - CASE SUMMARY: This work describes the diagnosis and successful treatment of a 2
year-old domestic cat infected with Leishmania species and presenting fever, and
ulcerative and nodular skin lesions after being treated for pyodermatitis for 1
year without clinical improvement. After anamnesis the cat was submitted to a
complete clinical examination. Blood was collected for determination of
haematological and biochemical parameters, detection of feline leukaemia virus
(FeLV), feline immunodeficiency virus (FIV), feline coronavirus (FCoV) and
Leishmania amastigotes. Fine-needle aspiration puncture from the skin nodules was
also performed. After definitive diagnosis the animal was treated and followed up
over a 2 year period. The animal tested negative for FIV-specific antibodies,
FeLV antigen and feline coronavirus RNA. Leishmania amastigotes in the skin
nodules were confirmed by cytology and molecular diagnosis. Treatment was
initiated with allopurinol, resulting in a slight clinical improvement. Thus, N
methyl-glucamine antimoniate was added and administered for 30 days, with
complete closure of the ulcerative lesions in the hindlimbs requiring a surgical
approach. Close monitoring of the patient in the following 24 months indicated
that combined therapy was safe and clinical cure was achieved without further
relapses or side effects. RELEVANCE AND NOVEL INFORMATION: Considering the
increasing number of feline leishmaniosis cases and the inconsistent results of
most therapeutic protocols described in the literature, the use of new
approaches, especially in refractory cases, is essential. Although the use of
allopurinol and N-methyl-glucamine antimoniate is off-label in cats, in this case
the combination treatment was followed by an extensive analytical monitoring,
supporting their safety and effectiveness.
PMID- 28491413
TI - Intra-parenchymal brainstem haemorrhage secondary to iatrogenic needle injury
after a parenteral injection in a cat.
AB - CASE SUMMARY: A 6-month-old female domestic shorthair cat was presented with
acute onset non-ambulatory right hemiparesis and horizontal nystagmus following
an injection attempt in the neck, during which the cat did not cooperate.
Magnetic resonance imaging (MRI) revealed a well-defined intra-axial lesion on
the right side of the myelencephalon. The lesion was T2-weighted hypointense and
T1-weighted hypointense to isointense to grey matter, non-contrast enhancing,
with perilesional oedema and signal void on T2*-weighted images. A linear
hyperintense lesion in the muscles of the right dorsolateral aspect of the neck
on short tau inversion recovery images was also observed. These MRI findings were
consistent with iatrogenic brainstem haemorrhage and a muscle needle tract. The
cat made a good recovery with just mild residual neurological deficits 6 weeks
after the injury. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the
first report of an iatrogenic brainstem needle injury in a cat and the first
report of a central nervous system iatrogenic trauma after a parenteral
injection. Care should be taken with neck parenteral injections, especially in
the cranial cervical area.
PMID- 28491412
TI - Distal polyneuropathy in an adult Birman cat with toxoplasmosis.
AB - CASE SUMMARY: A 6-year-old female spayed Birman cat presented with a history of
weight loss, stiff and short-strided gait in the pelvic limbs and reluctance to
jump, progressing to non-ambulatory tetraparesis over 6 weeks. Poor body
condition, dehydration and generalised muscle wastage were evident on general
examination. Neurological examination revealed mildly depressed mental status,
non-ambulatory flaccid tetraparesis and severely decreased proprioception and
spinal reflexes in all four limbs. The neuroanatomical localisation was to the
peripheral nervous system. Haematology, feline immunodeficiency virus/feline
leukaemia virus serology, serum biochemistry, including creatine kinase and
thyroxine, thoracic radiographs and abdominal ultrasound did not reveal
significant abnormalities. Electromyography revealed fibrillation potentials and
positive sharp waves in axial and appendicular muscles. Decreased motor
conduction velocities and compound muscle action potential amplitudes were
detected in ulnar and sciatic-tibial nerves. Residual latency was increased in
the sciatic-tibial nerve. Histologically, several intramuscular nerve branches
were depleted of myelinated fibres and a few showed mononuclear infiltrations.
Toxoplasma gondii serology titres were compatible with active toxoplasmosis. Four
days after treatment initiation with oral clindamycin the cat recovered the
ability to walk. T gondii serology titres and neurological examination were
normal after 11 and 16 weeks, respectively. Clindamycin was discontinued after 16
weeks. One year after presentation the cat showed mild relapse of clinical signs
and seroconversion, which again resolved following treatment with clindamycin.
RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the first report of
distal polyneuropathy associated with toxoplasmosis in a cat. This case suggests
the inclusion of toxoplasmosis as a possible differential diagnosis for acquired
polyneuropathies in cats.
PMID- 28491414
TI - Morphine-induced pruritus after epidural administration followed by treatment
with naloxone in a cat.
AB - CASE SUMMARY: A young male domestic shorthair cat weighing 1.6 kg was admitted to
a veterinary teaching hospital for elective orchiectomy. A lumbosacral epidural
injection of preservative-free morphine (0.1 mg/kg) and lidocaine (0.25 ml/kg)
was performed under general anesthesia. One hour after extubation, the cat became
agitated. Severe licking and biting of the hindlimbs, tail and lumbar area were
observed. Pruritus was suspected and likely to be caused by epidural morphine.
Acepromazine (0.02 mg/kg IM) was administered but clinical signs did not cease.
Naloxone (2 ug/kg IV) was administered and clinical signs resolved within 20
mins. RELEVANCE AND NOVEL INFORMATION: Different therapeutic approaches are
available for the treatment of morphine-induced pruritus. This case describes an
additional treatment option using opioid antagonism with naloxone.
PMID- 28491415
TI - Prevalence of selected infectious disease agents in stray cats in Catalonia,
Spain.
AB - OBJECTIVES: The objective of the current study was to investigate the prevalence
rates of the following infectious agents in 116 stray cats in the Barcelona area
of Spain: Anaplasma phagocytophilum, Bartonella species, Borrelia burgdorferi,
Chlamydia felis, Dirofilaria immitis, Ehrlichia species, feline calicivirus
(FCV), feline herpesvirus-1 (FHV-1), feline leukaemia virus (FeLV), feline
immunodeficiency virus (FIV), haemoplasmas, Mycoplasma species and Rickettsia
species. METHODS: Serum antibodies were used to estimate the prevalence of
exposure to A phagocytophilum, Bartonella species, B burgdorferi, Ehrlichia
species and FIV; serum antigens were used to assess for infection by D immitis
and FeLV; and molecular assays were used to amplify nucleic acids of Anaplasma
species, Bartonella species, C felis, D immitis, Ehrlichia species, FCV, FHV-1,
haemoplasmas, Mycoplasma species and Rickettsia species from blood and nasal or
oral swabs. RESULTS: Of the 116 cats, 63 (54.3%) had evidence of infection by
Bartonella species, FeLV, FIV or a haemoplasma. Anaplasma species, Ehrlichia
species or Rickettsia species DNA was not amplified from these cats. A total of
18/116 cats (15.5%) were positive for FCV RNA (six cats), Mycoplasma species DNA
(six cats), FHV-1 DNA (three cats) or C felis DNA (three cats). CONCLUSIONS AND
RELEVANCE: This study documents that shelter cats in Catalonia are exposed to
many infectious agents with clinical and zoonotic significance, and that flea
control is indicated for cats in the region.
PMID- 28491417
TI - Dorsally located corneal dermoid in a cat.
AB - CASE SUMMARY: A 2-month-old, male kitten was presented for evaluation of
unilateral blepharospasm and epiphora involving the right eye. Ocular examination
revealed conjunctivitis, a superficial corneal ulcer, reflex anterior uveitis and
a haired mass within the dorsal cornea of the right eye. The mass was
subsequently removed surgically via a lamellar keratectomy. Histologic evaluation
of the mass via light microscopy revealed it to be comprised of normal-haired
skin with mild inflammation. One week after surgical removal and medical
management of the corneal ulcer, all ocular clinical signs had resolved with
minimal corneal scarring. On re-examination 6 months following surgical excision
of the mass, the kitten was noted to be comfortable with no significant corneal
scarring. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the first
case report of a dorsally located corneal dermoid in a cat.
PMID- 28491416
TI - Hepatic fibrosarcoma incarcerated in a peritoneopericardial diaphragmatic hernia
in a cat.
AB - CASE SUMMARY: A 14-year-old, female neutered domestic shorthair presented for
dyspnoea. Thoracic ultrasonography and radiography showed that a heterogeneous
mass was present within the pericardial sac, and the mass continued caudally with
the mesenteric fat. On CT, the outline of the diaphragm was not continuous and
there was an obvious defect with diaphragmatic thickening present at the mid
level of the liver. A pleural effusion and a small-volume pericardial effusion
were also present. A ventral midline coeliotomy and median sternotomy revealed a
5 * 6 * 7 cm firm, irregular, tan-coloured soft tissue mass within the
pericardial sac attached to both the diaphragmatic defect and liver. The mass was
carefully dissected away from the heart and the diaphragmatic defect was repaired
with primary closure. Postoperatively, the cat had a persistent pneumothorax that
required continuous pleural suction for 41 h. The cat died 44 h postoperatively.
Histopathology and immunohistochemistry confirmed the mass to be a hepatic
fibrosarcoma incarcerated in a peritoneopericardial diaphragmatic hernia (PPDH).
RELEVANCE AND NOVEL INFORMATION: This is the first reported case of metaplastic
transformation of liver into a sarcoma in a cat with PPDH. In addition, hepatic
fibrosarcoma is a rarely reported location for fibrosarcoma in this species.
PMID- 28491418
TI - Hybrid technique coil embolisation for intrahepatic arterioportal fistula in a
cat: case report.
AB - CASE SUMMARY: A 13-month-old, female, mixed breed, 4.0 kg cat was referred with a
6 month history of decreased appetite, loss of vigour and intermittent vomiting.
Physical examination revealed no cyanosis or wasting, and no audible heart murmur
was auscultated. Blood profile revealed mild anaemia and mildly elevated
postprandial serum ammonia (109 ug/dl). Abdominal ultrasonography revealed
dilation of an intrahepatic portal vein branch and an intrahepatic aneurysm, with
splenomegaly and ascites. Hepatic arteriovenous fistula/hepatic artery-portal
vein fistula with multiple acquired portosystemic shunts was strongly suspected.
Medical control was achieved using antibiotics, liver-protecting agents, a low
protein diet and blood transfusions. However, because medical treatment proved
ineffective, coil embolisation was performed on day 11, using a hybrid approach
via the mesenteric vein. Subsequent follow-up showed good appetite, with no signs
of diarrhoea or ascites. Abdominal ultrasonography revealed that the mosaic
pattern around the site of coil placement in the portal vein branch had improved
and pulsatility had disappeared. RELEVANCE AND NOVEL INFORMATION: Intrahepatic
arterioportal fistula involves a circulatory shunt between the hepatic artery and
the hepatic or portal vein within the liver, and may be congenital or acquired.
Both forms have been reported in humans, but most cases in cats have been
congenital. Few reports have described treatment methods or prognosis in cats. We
report here that coil embolisation using a hybrid approach is a procedure
offering easy, effective treatment by blocking hepatofugal blood flow.
PMID- 28491419
TI - Retrograde migration and subcutaneous coiling of the peritoneal catheter of a
ventriculoperitoneal shunt in a cat.
AB - Case summary Ventriculoperitoneal shunt placement is the most commonly utilised
surgical treatment for hydrocephalus in human and veterinary patients. Migration
of the peritoneal catheter is an uncommon but well-documented complication in
people, usually occurring within the first 3 months postoperatively, although
only a single feline case report exists. A ventriculoperitoneal shunt was placed
in a domestic shorthair cat, aged 4 years and 10 months, following a diagnosis,
with MRI, of unilateral, non-communicating hydrocephalus. Diarrhoea, increased
vocalisation and pruritus were reported within the first 3 months
postoperatively. A shunt-associated seroma developed, which was aspirated under
ultrasound guidance. Within 3 days, the entire peritoneal catheter was
subcutaneously coiled at the level of the seroma. The peritoneal catheter was
replaced within the abdomen via a new subcutaneous tunnel. No further
complications had occurred 24 months following revision surgery. Relevance and
novel information This is the second report describing peritoneal catheter
migration in a cat. Repetitive head and neck movements during self-grooming,
raised intra-abdominal pressure secondary to vocalisation and tenesmus, and
negative pressure exerted during seroma aspiration may have contributed to
ventriculoperitoneal shunt migration. Excessive loose skin and increased activity
may further increase the risk of migration in cats. Diagnostic imaging should be
offered prior to and following aspiration of shunt-associated swellings, and
minimal negative pressure should be exerted. Attempts to reduce the frequency of
postoperative self-grooming, prevention and prompt treatment of conditions
predisposing to raised intra-abdominal pressure and moderate exercise
restriction, particularly within the first 3 months, may help reduce the risk of
peritoneal catheter migration.
PMID- 28491420
TI - Seroprevalence of feline immunodeficiency virus and feline leukaemia virus in
Australia: risk factors for infection and geographical influences (2011-2013).
AB - OBJECTIVES: Our aim was to: (i) determine the current seroprevalence of feline
immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) in three large
cohorts of cats from Australia; and (ii) investigate potential risk factors for
retroviral infection. METHODS: Cohort 1 (n = 2151 for FIV, n = 2241 for FeLV)
consisted of cats surrendered to a shelter on the west coast of Australia (Perth,
Western Australia [WA]). Cohort 2 (n = 2083 for FIV, n = 2032 for FeLV) consisted
of client-owned cats with outdoor access recruited from around Australia through
participating veterinary clinics. Cohort 3 (n = 169 for FIV, n = 166 for FeLV)
consisted of cats presenting to Murdoch University Veterinary Hospital for a
variety of reasons. Fresh whole blood was collected and tested using a
commercially available point-of-care lateral flow ELISA kit that detects p27 FeLV
antigen and antibodies to FIV antigens (p15 and p24) (cohorts 1 and 2), or one of
two lateral flow immunochromatography kits that detect p27 antigen and antibodies
to FIV antigen (p24 and/or gp40) (cohort 3). Data recorded for cats in cohort 2
included signalment, presenting complaint and postcode, allowing investigation of
risk factors for FIV or FeLV infection, as well as potential geographical 'hot
spots' for infection. RESULTS: The seroprevalence of FIV was 6% (cohort 1), 15%
(cohort 2) and 14% (cohort 3), while the seroprevalence of FeLV was 1%, 2% and 4%
in the same respective cohorts. Risk factors for FIV infection among cats in
cohort 2 included age (>3 years), sex (male), neutering status (entire males) and
location (WA had a significantly higher FIV seroprevalence compared with the
Australian Capital Territory, New South Wales and Victoria). Risk factors for
FeLV infection among cats in cohort 2 included health status ('sick') and
location (WA cats were approximately three times more likely to be FeLV-infected
compared with the rest of Australia). No geographical hot spots of FIV infection
were identified. CONCLUSIONS AND RELEVANCE: Both FIV and FeLV remain important
infections among Australian cats. WA has a higher seroprevalence of both feline
retroviruses compared with the rest of Australia, which has been noted in
previous studies. A lower neutering rate for client-owned male cats is likely
responsible for the higher seroprevalence of FIV infection in WA cats, while the
reason for the higher seroprevalence of FeLV in WA cats is currently unknown.
PMID- 28491421
TI - Medical management of gastrinoma in a cat.
AB - CASE SUMMARY: A 7-year-old male castrated domestic short-haired cat was evaluated
for a 4 week history of intermittent vomiting, ptyalism, lethargy and weight
loss. Serum biochemistry revealed mild mixed hepatopathy. Abdominal
ultrasonography identified multiple heterogeneous hepatic masses and a linear,
hyperechoic focus with associated reverberation artifact in the wall of the
stomach consistent with a gastric ulcer. Serum gastrin concentrations were
markedly increased. Cytologic interpretation of a fine-needle aspirate of the
hepatic masses was consistent with neuroendocrine neoplasia, and a diagnosis of
gastrinoma was established. Deterioration of the cat's condition, despite at-home
acid-suppressant therapy, led to hospitalization. The cat was initially
stabilized with intravenous crystalloid fluid therapy, maropitant, pantoprazole
and octreotide. A continuous radiotelemetric intragastric pH monitoring system
was used to monitor the response of intragastric pH to therapy. Long-term therapy
was continued with omeprazole (orally q12h), octreotide (subcutaneously q8h) and
thrice-weekly toceranib administered orally. Toceranib therapy led to
gastrointestinal upset and was discontinued. Gastric ulceration resolved within 8
weeks, and palliation of clinical signs was achieved for approximately 5 months.
RELEVANCE AND NOVEL INFORMATION: Including this report, only six cases of feline
gastrinoma have been reported in the veterinary literature. Little is known
regarding non-surgical therapy, and octreotide has not been previously reported
for medical management of feline gastrinoma. Results of intragastric pH
monitoring and clinical improvement suggest that medical therapy using octreotide
and proton pump inhibitors represents a novel therapeutic option for cats with
gastrinoma where surgical excision is not feasible.
PMID- 28491422
TI - Diagnosis of Aelurostrongylus abstrusus verminous pneumonia via sonography-guided
fine-needle pulmonary parenchymal aspiration in a cat.
AB - Case summary A 9-year-old, male neutered, indoor-outdoor domestic shorthair cat
from the northern Alabama countryside presented for a 3 week history of coughing,
lethargy and an episode of self-resolving dyspnea that occurred 1 week prior to
presentation. Three-view thoracic radiographs revealed a moderate-to-severe,
diffuse, mixed bronchial to structured interstitial (miliary-to-nodular)
pulmonary pattern in all lung lobes with peribronchial cuffing and multifocal
areas of mild patchy alveolar opacity. Ultrasound-guided evaluation and fine
needle aspiration of the caudodorsal lung parenchyma was performed with sedation.
Cytology revealed many widely scattered Aelurostrongylus abstrusus larvae and
ova. Upon the confirmed diagnosis of A abstrusus verminous pneumonia, treatment
with fenbendazole and selamectin resulted in complete resolution of clinical
signs within 6 weeks of the initial diagnosis. Relevance and novel information We
report herein the first documented case in the Americas of A abstrusus verminous
pneumonia diagnosed via cytologic evaluation of an in vivo, percutaneous
ultrasound-guided fine-needle aspirate of affected lung. Additionally, to our
knowledge, we offer the first account of the sonographic (pulmonary) features of
the disease.
PMID- 28491423
TI - Acromegaly in a non-diabetic cat.
AB - CASE SUMMARY: A 14-year-old, neutered male European shorthair cat was evaluated
for a routine health check. The owner did not report any clinical signs except
for respiratory stridor. On physical examination the main findings were broad
facial features and increased interdental spaces. On haematology, a mild, non
regenerative anaemia was detected, whereas the serum biochemistry profile and
urinalysis were unremarkable. The serum glucose concentration was within the
reference interval. Serum insulin-like growth factor-1 concentration was markedly
elevated (>1600 ng/ml). The basal serum growth hormone concentration was elevated
and decreased only mildly after somatostatin administration. Basal serum insulin
concentration was high, and the insulin concentration increased considerably
after glucose loading, consistent with insulin resistance. CT scanning of the
skull showed an enlarged pituitary gland and increased skull bone thickness. The
final diagnosis was acromegaly. RELEVANCE AND NOVEL INFORMATION: These findings
demonstrate that acromegaly should be pursued and suspected in cats other than
those with diabetes mellitus.
PMID- 28491424
TI - Accidental alfaxalone overdose in a mature cat undergoing anaesthesia for
magnetic resonance imaging.
AB - Case summary This case report describes the clinical signs and treatment of an
alfaxalone 10 times overdose in a 12-year-old cat undergoing anaesthesia for MRI.
The cat was discharged from hospital following a prolonged recovery including
obtunded mentation and cardiorespiratory depression for several hours following
cessation of anaesthesia. The cat received supportive therapy that included
supplemental oxygen via a face mask, intravenous crystalloid fluids and active
rewarming. The benefits of using alfaxalone for maintenance of anaesthesia, its
pharmacokinetics and previously reported lethal doses are discussed. Strategies
for reducing the incidence of medication errors are presented. Relevance and
novel information An unintentional overdose of alfaxalone by continuous rate
infusion has not been reported previously in a cat. Treatment is supportive and
directed towards maintenance of the cardiorespiratory systems. Whenever possible,
smart pumps that have been designed to reduce human error should be used to help
prevent medication errors associated with continuous rate infusions.
PMID- 28491425
TI - Lungworm Eucoleus aerophilus (Capillaria aerophila) infection in a feline
immunodeficiency virus-positive cat in France.
AB - CASE SUMMARY: A 2-year-old domestic shorthair female outdoor cat living in France
was diagnosed with a lungworm infection due to Eucoleus aerophilus. The history
and clinical signs, in association with bronchoscopic examination, suggested
chronic upper respiratory disease. Cytological examination of bronchoalveolar
lavage fluid (BALF) was consistent with suppurative bronchitis. Direct
microscopic examination of BALF enabled the identification of E aerophilus ova.
RELEVANCE AND NOVEL INFORMATION: The cat was positive for feline immunodeficiency
virus and had been treated with steroids for a suspected allergic bronchitis,
suggesting that immunodeficiency was probably a facilitating factor for E
aerophilus infection, as described in previous cases. This case report emphasises
the importance of considering eucoleosis (capillariosis) in the differential
diagnosis of respiratory disease in cats. To our knowledge, this is the first
clinical case of E aerophilus infection described in a domestic cat in France.
PMID- 28491426
TI - Stevens-Johnson syndrome/toxic epidermal necrolysis caused by cefadroxil in a
cat.
AB - CASE SUMMARY: A 5-year-old, spayed female, indoor-only domestic shorthair cat was
referred with an acute history of multifocal cutaneous and mucocutaneous erosive
ulcerative lesions and skin detachment. The lesions occurred on the seventh day
of therapy with cefadroxil. Erosive-ulcerative and occasionally crusted lesions
were apparent on the medial and lateral canthus of both eyes, ventral neck,
abdomen, perivulvar region, periungual skin and medial aspect of the front and
hindlimbs. Diffuse and severe exfoliation was present on the dorsum and tail base
and in both external ear canals. The cat was also dehydrated, tachycardic and
febrile. Histopathological examination revealed extensive epidermal ulceration,
interface dermatitis with vacuolar degeneration, apoptosis at multiple epidermal
levels and basal, suprabasal and spinous dermoepidermal detachment. The
histopathological diagnosis was consistent with Stevens-Johnson syndrome/toxic
epidermal necrolysis (SJS/TEN). The recently reported Algorithm of Drug Causality
in Epidermal Necrolysis (ALDEN), currently used in human medicine, was applied
and a score of +6 was calculated; this supported the view that SJS/TEN in this
cat was very likely to be associated with cefadroxil administration. RELEVANCE
AND NOVEL INFORMATION: This clinical communication reports cefadroxil as a very
probable cause of SJS/TEN in a cat; the ALDEN was applied in this case and
supported diagnosis.
PMID- 28491427
TI - Sinonasal aspergillosis in a British Shorthair cat in the UK.
AB - Case summary A 13-year-old, castrated male, British Shorthair cat presented for
investigation of chronic, intermittent, bilateral epistaxis and stertor. CT
revealed severe asymmetric bilateral intranasal involvement with extensive
turbinate lysis, increased soft tissue attenuation and lysis of the
sphenopalatine bone and cribriform plate. On retroflexed pharyngoscopy, a plaque
like mass occluded the choanae. Rostral rhinoscopic examination revealed
extensive loss of nasal turbinates, necrotic tissue and mucosal fungal plaques in
the left nasal cavity. The right nasal cavity was less severely affected. The
nasal cavities were debrided extensively of plaques and necrotic tissue.
Aspergillus fumigatus was isolated on fungal culture, and species identity was
confirmed using comparative sequence analysis of the partial beta-tubulin gene.
On histopathology of nasal biopsies, there was ulcerative lymphoplasmacytic and
neutrophilic rhinitis, and fungal hyphae were identified on nasal mucosa,
consistent with a non-invasive mycosis. The cat was treated with oral
itraconazole after endoscopic debridement, but signs relapsed 4.5 months from
diagnosis. Residual left nasal fungal plaques were again debrided endoscopically
and oral posaconazole was administered for 6 months. Fourteen months from
diagnosis, the cat remains clinically well with mild intermittent left nasal
discharge secondary to atrophic rhinitis. Relevance and novel information This is
the first case of rhinoscopically confirmed sinonasal aspergillosis to be
diagnosed in a cat in the UK. Endoscopic confirmation of resolution of infection
is useful in cases where mild nasal discharge persists after treatment.
PMID- 28491428
TI - Chronic intestinal pseudo-obstruction associated with enteric ganglionitis in a
Persian cat.
AB - Case summary A 7-year-old neutered male Persian cat was presented for acute
vomiting and inappetence. Physical examination revealed severe abdominal
distension. Radiographs demonstrated pneumoperitoneum, megaoesophagus and
generalised gaseous distension of the digestive tract. Exploratory coeliotomy was
performed, revealing markedly distended and thickened small and large intestines
with no observable peristalsis. No intestinal perforation was present.
Bacteriological and cytological analysis of abdominal fluid revealed a septic
peritonitis involving Pasteurella multocida. Full-thickness intestinal biopsies
demonstrated lymphocytic ganglioneuritis localised to the enteric nervous system,
in association with glandular atrophy and muscular layer hypertrophy. Amoxicillin
clavulanate and analgesics were given. The cat's general condition gradually
improved after the addition of pyridostigmine bromide (0.5 mg/kg q12h PO),
initiated 3 days postsurgery. Vomiting resolved and did not recur. Follow-up
radiographs at 15 days, and 1 and 6 months showed persistent intestinal ileus,
milder than on the pretreatment radiographs. Thirty months after presentation the
cat is still alive, without clinical signs, and receives 1 mg/kg q12h
pyridostigmine. Relevance and novel information To our knowledge, this is the
first case of ganglioneuritis of the myenteric plexus described in cats, as well
as the first one successfully treated with pyridostigmine. Chronic intestinal
pseudo-obstruction is a very rare condition in cats but should be included in the
differential diagnosis of generalised gastrointestinal ileus.
PMID- 28491429
TI - Prevalence of Cytauxzoon felis infection in healthy free-roaming cats in north
central Oklahoma and central Iowa.
AB - Case summary Cytauxzoonosis is a tick-borne disease of cats, and Oklahoma (OK),
USA, is considered an enzootic state. To determine the prevalence of Cytauxzoon
felis, blood was collected from free-roaming cats, as they are frequently exposed
to tick vectors. Our objective was to determine the prevalence of C felis
infection in free-roaming cats in north-central Oklahoma and central Iowa (IA).
Infection with C felis was determined using DNA extracted from blood and PCR
amplification. Blood was collected from 380 free-roaming cats between January and
April in 2014 in OK. DNA from C felis was detected in 3/380 (0.8%; 95%
confidential interval [CI] 0.22-2.3%). In IA, 292 blood samples were collected
between 2012 and 2014. No C felis-infected cats were detected (0; 95% CI 0-0%).
Relevance and novel information The prevalence of C felis (0.8%) in north-central
OK reported herein was lower than the previously reported 3.4% in domestic cats
in OK. Our study supports that the prevalence in a given enzootic area can vary
by location and from the pool of cats sampled. None of 291 (0%) cats were
infected with C felis in central IA. To date, only one case of cytauxzoonosis in
a domestic cat has been reported in IA. It is important to monitor cats for C
felis infections in northern US states, as geographic distribution of Amblyomma
americanum expands northward. As free-roaming cats have more contact with the
tick vectors of C felis, this population allows us to monitor the expansion of C
felis distribution.
PMID- 28491431
TI - Hyperinsulinaemic, hypoglycaemic syndrome due to acquired nesidioblastosis in a
cat.
AB - Case summary A 6-year-old, neutered female British Shorthair cat presented with
acute-onset weakness and mental dullness. Initially the cat was mildly
hyperglycaemic (9.9 mmol/l; reference interval [RI] 3.3-6.7 mmol/l). Over the
following 12 h the cat developed central blindness, tremors, intermittent
seizures and opisthotonus. Repeat blood sampling revealed a marked hypoglycaemia
(0.8 mmol/l). Insulin level (performed on a serum sample collected while the cat
was hypoglycaemic) was inappropriately elevated (1575 mIU/l; RI 10-80 mIU/l). An
abdominal ultrasound was unremarkable. An exploratory laparotomy revealed a firm
and erythematous left limb of the pancreas. Following surgical resection of the
left limb of the pancreas, the cat returned to a euglycaemic state after a brief
rebound hyperglycaemia. Histopathology revealed pancreatic fibrosis with marked
multifocal micronodular hyperplasia of exocrine and endocrine cells.
Synaptophysin immunohistochemistry confirmed nodular beta-cell hyperplasia.
Relevance and novel information Nesidioblastosis describes a syndrome of acquired
hyperinsulinaemia and associated hypoglycaemia secondary to focal or diffuse (non
neoplastic) beta-cell hyperplasia within the pancreas. Acquired nesidioblastosis
has been reported in humans, where beta-cell dysregulation is thought to occur in
response to pancreatic injury. This is the first reported case of clinically
significant hypoglycaemia due to acquired nesidioblastosis in an adult domestic
cat. While this condition is rare, nesidioblastosis is being increasingly
recognised in humans and it is an important differential diagnosis to consider
when investigating hypoglycaemia as it cannot be distinguished from insulinoma
without histopathological evaluation. While recurrence has been occasionally
reported in humans, the prognosis is considered good.
PMID- 28491432
TI - Renal transitional cell carcinoma with bilateral ocular metastasis in a cat.
AB - Case summary A 4-year-old, spayed female, domestic shorthair cat was presented
for evaluation due to a 4 day history of inappetence and lethargy. Physical
examination revealed mild dehydration and blindness of the left eye. Abnormal
imaging findings included a well-margined soft tissue mass with irregular central
cavity located in the dorsal aspect of the caudal lung lobe. Cytological
examination of the mass revealed chronic inflammation with hemorrhage. Tests for
parasitic and fungal diseases were negative. Ophthalmic examination 17 days after
the cat was initially presented revealed severe diffuse pathology of both
retinas. Left renomegaly was noted 22 days after the initial presentation, and
cytological examination of samples obtained from the right vitreous, left kidney
and the pulmonary mass yielded atypical epithelial cells exhibiting malignant
changes. Post-mortem examination following euthanasia revealed renal transitional
cell carcinoma with metastasis to both eyes, lungs and skeletal muscle.
Immunohistochemical evaluation of the neoplastic cells in the eye revealed
moderate cytoplasmic reactivity for CK7. CK20 immunohistochemistry was negative.
Relevance and novel information To the best of our knowledge, this is the first
report of renal transitional cell carcinoma with ocular metastasis in a cat. In
addition, this report describes immunohistochemistry results of transitional cell
carcinoma in a cat using CK7 and CK20.
PMID- 28491433
TI - Evaluation of rapid diagnostic test kits for feline leukemia virus infection
using samples from naturally infected cats.
AB - OBJECTIVES: Feline leukemia virus (FeLV) is a potentially life-threatening
oncogenic retrovirus. The p27 viral core protein is produced by the virus in
infected feline cells, is found in the cytoplasm in several blood cells and can
be free in the serum and plasma. ELISA or particle-based immunoassay are commonly
used to detect the presence of the p27 core protein in samples obtained from
blood. The objective of this study was to compare the performance of several in
clinic tests: the SNAP Feline Triple Test (IDEXX Laboratories), the WITNESS FeLV
FIV Test (Zoetis) and the VetScan Feline FeLV/FIV Rapid Test (Abaxis). METHODS:
The sample population (100 positive, 105 negative samples) consisted of serum and
plasma samples submitted to IDEXX's worldwide reference laboratory for feline
retrovirus testing. Virus isolation and reverse transcriptase PCR results were
not available and so samples were judged to be positive or negative based on the
results of the ViraCHEK FeLV (Zoetis) microtiter plate assay. RESULTS: The
percentage of samples positive and negative for FeLV p27 antigen using the three
in-clinic tests compared with the ViraCHEK method were as follows: IDEXX Feline
Triple (positive 98.0%, negative 100%); Zoetis WITNESS (positive 79.0%, negative
97.1%); Abaxis VetScan (positive 73.0%, negative 97.1%). CONCLUSIONS AND
RELEVANCE: The SNAP Feline Triple Test demonstrated a high level of agreement for
FeLV-positive and FeLV-negative samples when assessed in this model. Results of
FeLV assays can vary among tests.
PMID- 28491434
TI - Life-threatening haematological complication occurring in a cat after chronic
carbimazole administration.
AB - CASE SUMMARY: An 11-year-old spayed female domestic shorthair cat with a history
of hyperthyroidism treated with carbimazole for 7 months was presented for a
check-up after a few episodes of vomiting. The cat had been receiving
prednisolone at 0.5 mg/kg PO q12h for recent pancreatitis and concurrent
inflammation of liver and small intestines confirmed by biopsies. Clinical
examination revealed pale mucous membranes with a capillary refill time of <2 s.
Haematology showed severely decreased packed cell volume (16%), and increased
prothrombin time (42 s), partial thromboplastin time (>120 s) and fibrinogen
serum concentration (3.5 g/l). Morphological changes of thrombocytes in the
absence of thrombocytopenia were also noted. In-saline agglutination test was
positive. Abdominal radiographic and ultrasonographic examinations excluded the
presence of organ abnormalities and peritoneal effusion. Blood biochemistry was
unremarkable. Feline leukaemia virus and feline immunodeficiency virus tests were
negative. On the basis of these findings, immune-mediated anaemia secondary to
chronic carbimazole administration was suspected. Prednisolone was increased to 2
mg/kg PO q24h and carbimazole tablets were stopped. Despite close monitoring and
intensive care, the cat died the same evening of admission to the hospital.
RELEVANCE AND NOVEL INFORMATION: This report suggests that severe haemotoxicity
may occur as a sequel of chronic carbimazole administration in cats. Routine
bloodwork and accurate follow-up of cats under treatment with thyrotoxic therapy
may be advisable, in order to detect haematological changes before lethal
complications occur.
PMID- 28491435
TI - Scapular osteomyelitis in an immature domestic shorthair cat.
AB - CASE SUMMARY: A 12-week-old, male, domestic shorthair cat was presented with
severe left thoracic limb lameness. Investigation included physical examination,
diagnostic imaging with radiography and CT, histopathology and microbiological
culture. Physical examination revealed a large, firm mass on the left scapula.
Radiography and CT showed a monostotic spherical expansile bone lesion in the
infraspinatus fossa of the left scapula. The histopathological description was a
central acute suppurative osteomyelitis with reactive fibrosis and new bone
formation at the periphery. Aerobic and anaerobic cultures were negative and the
underlying cause of the osteomyelitis could not be identified. The use of broad
spectrum antibiotics for 8 weeks proved effective with full clinical recovery and
no signs of relapse during the follow-up time of 8 months. RELEVANCE AND NOVEL
INFORMATION: This report describes the management and outcome of a rare case of
osteomyelitis with severe deformation of scapular bone morphology in an immature
cat that was treated successfully with full recovery of limb function and
restored integrity of the scapula.
PMID- 28491436
TI - Primary bronchial carcinoma associated with bone marrow metastasis and
paraneoplastic monoclonal gammopathy in a cat.
AB - CASE SUMMARY: Herein we describe an unusual metastatic pattern and paraneoplastic
manifestation of a bronchial carcinoma in a cat. An 8 year-old cat presented with
a diminished appetite, dysphagia, weight loss, lethargy and coughing. Thoracic
radiographs revealed a lung mass. Bronchial carcinoma was diagnosed on the basis
of histology and was associated with a lymphoplasmocytic infiltration of the
fibrovascular stroma. Biochemistry showed hyperproteinaemia. Serum protein
electrophoresis showed a narrow spike in the gamma region. Bone marrow cytology
revealed an infiltrate with numerous clustered epithelial cells. The cat was
euthanased 2 months later because of anorexia and poor general condition.
RELEVANCE AND NOVEL INFORMATION: To the best of our knowledge, this is the first
clinical description of primary bronchial carcinoma associated with bone marrow
metastases and paraneoplastic monoclonal gammopathy in a cat.
PMID- 28491437
TI - Hypersensitivity reaction associated with subcutaneous glargine insulin therapy
in a cat.
AB - CASE SUMMARY: A 14-year-old, domestic shorthair cat was treated for transient
diabetes mellitus for 3 months with glargine insulin, which was discontinued when
the diabetes mellitus resolved. Approximately 36 months later the diabetes
mellitus recurred and glargine insulin was restarted. Within 2-3 mins of the
first injection the cat collapsed, developed profuse vomiting and diarrhea, as
well as facial swelling and diffuse erythema. A hypersensitivity reaction was
suspected and the cat was treated with antihistamines, aggressive fluid therapy
and gastrointestinal support. The cat made a full recovery and was discharged 3
days later. Six months later the cat re-presented for relapse of its diabetes
mellitus and an intradermal skin challenge with 1:20 diluted insulin was
performed confirming a hypersensitivity to glargine. The cat continues to be well
regulated on porcine zinc insulin without any hypersensitivity reactions noted.
RELEVANCE AND NOVEL INFORMATION: Hypersensitivity reactions to insulin
administration are rarely described in human medicine. This is the first reported
case of a hypersensitivity reaction secondary to glargine insulin in a cat.
Clinicians should be aware of this potential complication, particularly in
animals with a previous history of insulin administration and the potential to
utilize intradermal testing with insulin.
PMID- 28491438
TI - Isolated unilateral absence of the right pulmonary artery in two cats visualized
by computed tomography angiography.
AB - CASE SERIES SUMMARY: Two cats were evaluated for progressive exercise
intolerance, dyspnea and unilateral infiltrate of the left lung. Computed
tomography angiography (CTA) revealed absence of the right pulmonary artery in
both cats with systemic arterial collateral vessels perfusing the right segmental
pulmonary arteries. In one case, the collateral vessels arose from the esophageal
artery, while in the other case they derived off the right costocervical trunk.
One cat was diagnosed with pulmonary hypertension and was euthanized owing to
progressive respiratory distress despite medical management with sildenafil,
pimobendan, clopidogrel and furosemide. The other cat, without echocardiographic
evidence of pulmonary hypertension, was successfully managed with furosemide and
enalapril for more than 4 years. RELEVANCE AND NOVEL INFORMATION: CTA allowed
visualization of a rare congenital heart malformation, unilateral absence of the
right pulmonary artery, in two cats and accurately characterized the source of
collateral blood supply to the affected lung. Severe pulmonary hypertension may
be a negative prognostic factor in cats with this condition as medical therapy in
the cat without evidence of pulmonary hypertension resolved clinical signs, while
the cat with severe pulmonary hypertension died from the disease.
PMID- 28491439
TI - Mycobacterial panniculitis caused by Mycobacterium thermoresistibile in a cat.
AB - CASE SUMMARY: A domestic shorthair cat was evaluated for chronic, bilateral,
ulcerative dermatitis affecting the inguinal region and lateral aspects of both
pelvic limbs. Histopathologic examination of skin biopsies collected throughout
the course of disease revealed chronic pyogranulomatous ulcerative dermatitis.
Aerobic bacterial skin cultures yielded growth of a methicillin-resistant
Staphylococcus aureus and Corynebacterium amycolatum. Upon referral the clinical
findings were suggestive of a non-tuberculous Mycobacterium species infection.
Previously obtained skin cultures failed to yield growth of mycobacterial
organisms. A deep skin biopsy was collected and submitted for mycobacterial
culture. At 5 weeks of incubation Mycobacterium thermoresistibile was isolated.
In previous reports, M thermoresistibile has been isolated after 2-4 days of
incubation, suggesting that this strain may have been a slower growing variant,
or other factors (such as prior antimicrobial therapy) inhibited rapid growth of
this isolate. The cat was hospitalized for intravenous antibiotic therapy,
surgical debridement of wounds, vacuum-assisted wound closure therapy and
reconstruction procedures. The wounds were ultimately primarily closed and the
cat was discharged to the owner after 50 days of hospitalization. Seven months
after hospitalization, the ulcerative skin lesions had healed. RELEVANCE AND
NOVEL INFORMATION: To our knowledge, only two cases of M thermoresistibile
panniculitis have been reported in cats. In the only detailed report of feline M
thermoresistibile panniculitis, treatment was not attempted. The second case only
reported detection of M thermoresistibile by PCR without a clinical description
of the case. In our case report, severe chronic skin infection with M
thermoresistibile was addressed using prolonged specific antibiotic therapy,
surgical debridement and reconstructions, and treatment of secondary bacterial
infections.
PMID- 28491440
TI - Marginal resection and adjuvant strontium plesiotherapy in the management of
feline eyelid malignant peripheral nerve sheath tumours: two cases.
AB - CASE SERIES SUMMARY: Two cats with a marginally resected eyelid malignant
peripheral nerve sheath tumour were treated with adjuvant strontium plesiotherapy
a few weeks after surgery. The dose applied in both cases was 200 Gy to the
surface, in five fractions, on a Monday-Wednesday-Friday basis. The treatment
aimed to achieve a clinical margin of approximately 1 cm around the surgical scar
and multiple application fields were required to cover such an area. Local
recurrence was not seen in either case after 1330 and 645 days, respectively.
RELEVANCE AND NOVEL INFORMATION: The majority of periocular malignant peripheral
nerve sheath tumours reported in the literature recur after surgery. In the two
cases described in this report the combination of surgery and adjuvant
plesiotherapy has been able to provide good local control with minimal toxicity.
This multimodal approach could be considered as an alternative to aggressive
surgery such as enucleation or exenteration.
PMID- 28491441
TI - Successful treatment of vaginal malakoplakia in a young cat.
AB - CASE SUMMARY: A 3-year-old, female, spayed, domestic shorthair cat presented for
dysuria and haematuria, unresponsive to antibiotic treatment. A small, fleshy,
erythematous mass protruded from the vaginal vault. Ultrasound identified a
vaginal mass effect with mixed echogenicity measuring in excess of 3 cm.
Vaginoscopy confirmed an extensive, fleshy, irregular mass that was characterised
histologically as pyogranulomatous vaginitis, with periodic acid-Schiff-positive
macrophages containing gram-negative bacteria. Fluorescence in situ hybridisation
analysis demonstrated invasive intracellular Escherichia coli. Vaginal
malakoplakia was diagnosed. Tissue culture and antimicrobial susceptibility of E
coli was used to guide treatment. A 6 week course of enrofloxacin 5 mg/kg q24h
resulted in complete resolution of the mass and clinical signs. RELEVANCE AND
NOVEL INFORMATION: Malakoplakia is a rare chronic inflammatory condition that has
been previously reported in the bladder of two cats. The pathogenesis of
malakoplakia is thought to involve ineffective killing of bacteria (eg. E coli),
similar to granulomatous colitis in Boxers and French Bulldogs. The literature on
malakoplakia in cats is sparse. This is the first reported feline case with
vaginal involvement, intracellular E coli and successful treatment with a
fluoroquinolone. Malakoplakia is an important, non-neoplastic differential
diagnosis when a mass is identified in the urogenital system of a young cat.
PMID- 28491442
TI - Respiratory distress associated with lungworm infection in a kitten.
AB - CASE SUMMARY: A 5-month-old feral kitten developed worsening respiratory signs,
including tachypnea, coughing and wheezing after standard anthelmintic treatment
with fenbendazole at a local shelter. The kitten was referred to the University
of California, Davis, William R Pritchard Veterinary Medicine Teaching Hospital
for further evaluation. Thoracic radiographs revealed a severe diffuse
bronchointerstitial pattern with bronchial cuffing, ill-defined nodules and
lymphadenomegaly. Differentials included infectious etiologies such as
toxoplasmosis, feline infectious peritonitis and cryptococcosis. Parasitic
infection was considered less likely, owing to previous anthelmintic treatment.
Bronchoalveolar lavage revealed marked neutrophilic and eosinophilic
inflammation, and parasitic larvae were observed in a swab of trachea mucus. PCR
confirmed the larvae as Aelurostrongylus abstrusus. The kitten recovered with two
more rounds of anthelmintic treatment. RELEVANCE AND NOVEL INFORMATION: Parasitic
pneumonia should be considered as a cause of respiratory distress in kittens and
cats. Lungworm infections have been more commonly reported in free-roaming young
and adult cats, but cannot be excluded as a differential diagnosis in cats from
varied environments and in kittens. Kittens appear to be especially sensitive to
lungworm infections, manifested by the development of more severe clinical signs;
thus lungworm infection should always be considered when presented with a kitten
in respiratory distress. In the absence of cytologic confirmation of infection
via bronchoalveolar lavage or oropharyngeal swab, PCR provides a valuable means
for identification of lungworms, such as A abstrusus and Troglostrongylus
brevior.
PMID- 28491443
TI - CT findings in two cats with broncholithiasis.
AB - CASE SERIES SUMMARY: Chronic inflammatory airway disease with secondary
broncholithiasis was diagnosed in two cats from CT and bronchoalveolar lavage
cytological findings. In one cat with progressively worsening lower respiratory
tract signs, more than 80 discrete, highly attenuating endobronchial opacities
were detected on thoracic CT. The broncholiths were distributed throughout the
right middle, and left and right caudal lung lobes, and the caudal part of the
left cranial and accessory lobes. In the other cat broncholithiasis was an
incidental finding on thoracic radiographs taken during diagnostic investigation
of inappetence. On thoracic CT, 25 calcified endobronchial opacities were
detected in the left caudal lung lobe in secondary and tertiary bronchi. CT
features of chronic inflammatory airway disease were present in both cases,
including bronchiectasis, atelectasis, flattening of the diaphragm and bronchial
wall thickening. RELEVANCE AND NOVEL INFORMATION: This is the first report to
document CT features of broncholithiasis in cats. Feline broncholithiasis should
be considered as a differential diagnosis in any case where calcified
endobronchial material is evident on thoracic radiographs or CT.
PMID- 28491444
TI - Cerebral pyogranulomatous encephalitis caused by Cladophialophora bantiana in a
15-week-old domestic shorthair kitten.
AB - CASE SUMMARY: A case of cerebral phaeohyphomycosis caused by Cladophialophora
bantiana is described in a 15-week-old domestic shorthair kitten. RELEVANCE AND
NOVEL INFORMATION: Cerebral phaeohyphomycosis is a rare condition in cats caused
by dematiaceous fungi. This report describes the clinical and histopathological
findings in the youngest case documented in a feline, provides a brief review of
aetiology, diagnosis, treatment and prognosis of cerebral phaeohyphomycosis and
demonstrates the importance of molecular diagnostics in accurate mycotic species
identification.
PMID- 28491445
TI - Primary adrenal lymphoma causing hypoaldosteronism in a cat.
AB - CASE SUMMARY: A 10-year-old, 5.1 kg (11.2 lb), male castrated cat was presented
with signs of lethargy and decreased appetite at home after being previously
healthy. Serum biochemical analysis identified normokalemia (5.1 mmol/l;
reference interval [RI] 3.4-5.6 mmol/l) and severe hyponatremia (123 mmol/l; RI
145-158 mmol/l), with an Na/K ratio of 24 (RI 32-41). Baseline serum cortisol was
low to normal, but serum aldosterone was markedly decreased with a pre
adrenocorticotropic hormone stimulation concentration of 13 pmol/l (RI 194-388
pmol/l) and post-adrenocorticotropic hormone stimulation concentration of 21
pmol/l (RI 277-721 pmol/l). Hematologic and biochemical analyses were otherwise
unremarkable. Abdominal ultrasound revealed bilaterally enlarged adrenal glands
with no other abnormalities noted; thoracic radiographs also did not identify any
signs of metastasis. Fine-needle aspiration was strongly suggestive of lymphoma
of the adrenal glands, and PCR for antigen receptor rearrangement was positive
for B-cell clonal expansion; based on these findings, a diagnosis of primary
adrenal B-cell lymphoma was made. Stable disease was achieved for a short period
of time following vincristine, cyclophosphamide, prednisolone and fludrocortisone
therapy, followed by progressive adrenal enlargement and electrolyte derangements
that responded to neither doxorubicin nor adjustments in fludrocortisone dosage.
Ultrasonographic metastasis was not identified at any time, and other organ
derangements were not noted on hematologic or biochemical analyses. The cat was
euthanized 55 days after initial presentation. RELEVANCE AND NOVEL INFORMATION:
This is the first report of primary adrenal lymphoma in a cat, with presenting
signs compatible with hypoaldosteronism. Lymphoma should be a differential for
cats presenting with adrenal enlargement or clinical signs and biochemical
changes consistent with hypoaldosteronism or hypoadrenocorticism.
PMID- 28491446
TI - Severe muscle fasciculations and tremor in a cat with hypochloraemic metabolic
alkalosis secondary to duodenal obstruction.
AB - CASE SUMMARY: An 18-month-old, female spayed, Australian Mist cat presented with
a 24 h history of muscle tremors and inappetence progressing to collapse with
generalised muscle fasciculations. The cat was diagnosed with a hypochloraemic
metabolic alkalosis due to a duodenal foreign body found to be a trichobezoar at
coeliotomy. The cat made a complete recovery after enterotomy to remove the
trichobezoar, with cessation of neuromuscular clinical signs and normalisation of
its electrolyte and acid-base imbalances. RELEVANCE AND NOVEL INFORMATION: Muscle
fasciculations and tremors in cats can be caused by intoxications, metabolic
derangements, encephalomyelitis, feline hyperaesthesia syndrome and cerebellar
diseases. The presenting clinical signs of severe muscle fasciculations and
tremors have not previously been reported in association with an intestinal
obstruction in the cat.
PMID- 28491447
TI - Successful treatment of multifocal pedal Prototheca wickerhamii infection in a
feline immunodeficiency virus-positive cat with multiple Bowenoid in situ
carcinomas containing papillomaviral DNA sequences.
AB - CASE SUMMARY: A 16-year-old, castrated male, feline immunodeficiency virus (FIV)
positive, domestic shorthair cat developed multiple skin lesions. Most of these
were Bowenoid carcinoma in situ and contained DNA sequences consistent with Felis
catus papillomavirus type 2. Two additional lesions that developed in the skin
and subcutaneous tissues between the digital and carpal pads on the left forelimb
and right hindlimb were shown by cytology, histology and culture to be caused by
Prototheca wickerhamii. These lesions failed to improve in response to systemic
therapy treatment with itraconazole, but excision by sharp en bloc resection with
follow-up oral itraconazole therapy proved curative for one lesion, although the
other lesion recurred, necessitating a second surgery. RELEVANCE AND NOVEL
INFORMATION: This is only the second reported case of feline protothecosis from
Australia and the first case that has been cultured and identified to the species
level. Also of great interest was the presence of multiple papillomavirus
associated neoplastic lesions, which may have afforded a portal of entry for the
algal pathogen and the cat's positive FIV status; the latter might have impacted
on both viral and algal pathogenesis by effects on immunocompetence.
PMID- 28491448
TI - Multimodal non-surgical treatment of a feline tracheal adenocarcinoma.
AB - CASE SUMMARY: A 10-year-old, castrated male domestic shorthair cat presented with
a 2-3 month history of weight loss, lethargy and coughing. Thoracic radiographs
revealed a soft tissue opacity overlying the dorsal trachea from the first rib to
second rib and the ventral aspect of the trachea extending from the second rib to
approximately the fourth rib. CT confirmed a mass involving the dorsal, right
lateral and ventral aspects of the trachea narrowing the lumen and extending from
vertebra C7 through T4. Bronchoscopy revealed a partially circumferential
irregular and multilobulated tracheal mass, which was biopsied. The
histopathological diagnosis was tracheal adenocarcinoma. The cat was treated with
a definitive course of external beam radiation therapy (RT; 3 Gy * 18), cytotoxic
chemotherapy, a tyrosine kinase inhibitor and palliative RT. The cat remained
asymptomatic for 2 months and the mass remained stable radiographically for 11
months after RT. RELEVANCE AND NOVEL INFORMATION: With multimodal treatment the
cat had a survival time of 755 days. Initial treatment included definitive RT,
carboplatin and piroxicam, followed by toceranib phosphate and palliative RT when
the mass recurred. This case report describes the first documented use of non
surgical treatment and long-term outcome of tracheal adenocarcinoma in a cat.
This case report is an indication that prolonged survival can be achieved with
multimodal therapy.
PMID- 28491449
TI - Metastatic pulmonary carcinomas in cats ('feline lung-digit syndrome'): further
variations on a theme.
AB - CASE SERIES SUMMARY: The aim of this retrospective case series was to describe
seven cases where cats with primary lung tumours were presented because of
metastases to extra-pulmonary sites ('feline lung-digit syndrome'). Specifically,
we wanted to emphasise less typical case descriptions where tumour emboli
resulted in lesions developing in the musculature (including the muscles of the
head), skin or distal aorta. RELEVANCE AND NOVEL INFORMATION: The cases are
presented to increase clinical awareness of this entity in feline practice,
especially when characteristic combinations of clinical signs are present. When
clinicians have a high index of suspicion for these presentations, radiology
(thorax and digits) or ultrasound (distal aorta), combined with collection of
fine needle aspirate specimens for cytology, are usually sufficient to secure a
definitive diagnosis. Novel information in this series includes CT and MRI
findings from some cases. Typically, needle aspiration or biopsy targeting the
skin, digits and lesions in musculature is far easier compared with sampling the
primary tumour site in the lungs. The differential diagnosis and investigation of
multiple digital lesions is also considered.
PMID- 28491452
TI - Renal oncocytoma in a cat with chronic renal failure.
AB - CASE SUMMARY: A 9-year-old male neutered domestic shorthair cat presented with
anorexia. Ultrasonography showed an irregularly shaped hypoechoic mass in the
cranial pole of the right kidney. Ultrasound-guided fine-needle aspiration of the
renal mass was performed. Cytology revealed moderate cellularity smears composed
of epithelial cell clusters, which consisted of an exclusive population of
oncocytic cells seen in sheets and papillary clusters along with abundant single
cells. A moderate-to-abundant amount of densely stained granular cytoplasm with
round nuclei and indistinct nucleoli was seen. The cytological diagnosis was
renal oncocytic neoplasm. CT and surgical resection revealed a firm tan mass in
the right kidney. A final diagnosis of renal oncocytoma was made on the basis of
histology, immunohistochemical staining profile (positive for cytokeratin, and
negative for chromogranin A, neuron-specific enolase and vimentin) of neoplastic
cells, together with the electronic microscopy results. RELEVANCE AND NOVEL
INFORMATION: We believe that this is the first report of the cytological features
of feline renal oncocytoma.
PMID- 28491450
TI - Contribution of oral triamcinolone to treating proliferative and necrotising
otitis externa in a 14-year-old Persian cat.
AB - CASE SUMMARY: A 14-year-old female spayed cat was referred for recurrent otitis
externa and unusual proliferative lesions in both ear canals. The affected pinnae
and external ear canals were covered with large reddish-to-dark-brown verrucous
and necrotic tissue. Friable material and exudates occluded both ear canals.
Proliferative lesions developed in both ears 2-3 weeks before referral. The
histopathological diagnosis from two biopsies obtained from the friable materials
with endoscopic biopsy forceps was proliferative and necrotising otitis externa
(PNOE). Treatment was initiated with once-daily application of a potent topical
glucocorticoid (mometasone furoate) to both ears. Although the auricle and
vertical ear canals responded well, no improvement was seen in the horizontal
part of the ear canal after 9 weeks. Therefore, oral triamcinolone (0.9 mg/kg
q24h) was added for 1 week, and was then tapered (q48h) for 3 weeks. Most lesions
resolved, and after a further 2 weeks of prednisolone (2 mg/kg q48h) there was
complete resolution. No recurrence was observed during a 2 year follow-up period.
RELEVANCE AND NOVEL INFORMATION: PNOE commonly occurs in kittens, but it can
develop in older cats. To our knowledge, the PNOE in this case is the oldest age
of onset reported. This condition is rare and was only described recently, and
therapeutic options appear limited. According to previously published reports,
steroid therapy is ineffective, and tacrolimus is the only treatment known to
achieve resolution. However, oral and topical glucocorticoids were beneficial in
this case.
PMID- 28491453
TI - Surgical management of medial humeral epicondylitis, cubital synovial
osteochondromatosis and humeroradial subluxation in a cat.
AB - CASE SUMMARY: A 13-year-old domestic shorthair cat presented for evaluation of
pain and difficulty ambulating. Orthopedic examination and CT facilitated a
diagnosis of bilateral elbow synovial osteochondromatosis with medial humeral
epicondylitis and concurrent osteoarthritis. Right humeroradial subluxation was
evident on CT images, but no instability was evident preoperatively. Surgical
treatment was elected, including external neurolysis of the ulnar nerve, removal
of the areas of mineralization within the flexor carpi ulnaris muscle and medial
arthrotomy to remove intra-articular mineralized bodies. Following closure,
instability of the right elbow was noted with humeroradial subluxation
necessitating placement of circumferential suture prostheses to provide
satisfactory stability. Reassessment was performed 2, 6, 12, 24 and 40 weeks
postoperatively and revealed maintenance of elbow stability and substantial
improvement in mobility and comfort. RELEVANCE AND NOVEL INFORMATION: While
humeroradial subluxation has been reported in association with medial humeral
epicondylitis on post-mortem examination, associated clinically significant
instability has not been documented previously. Surgeons should be aware of the
potential for this complication and check elbow stability following surgery.
Despite this complication, a favorable medium-term outcome was achieved for this
cat.
PMID- 28491454
TI - Crossed fused renal ectopia in a Persian cat.
AB - CASE SUMMARY: This report describes a rare case of crossed fused renal ectopia
(CFRE) in a cat. A mature intact male Persian cat presented with bloody nasal
discharge and ascites. Diagnostic studies revealed an ectopic left kidney fused
with an orthotopic right kidney and a concurrent feline infectious peritonitis
(FIP) infection. The FIP was responsible for clinical signs in this cat, while
clinical signs associated with CFRE were not obvious. Despite receiving intensive
treatment, the cat died. A post-mortem examination was not performed because the
owners declined approval. RELEVANCE AND NOVEL INFORMATION: To the best of our
knowledge, this is the first report of L-shaped CFRE in a cat. In addition, this
report describes the CT features of L-shaped CFRE in a cat.
PMID- 28491456
TI - JFMS Open Reports: new look, new 'Collections'.
PMID- 28491455
TI - Use of adjunctive prednisolone in the management of a cat with bilateral
quadriceps contracture following trauma.
AB - CASE SUMMARY: A 6-month-old cat was successfully treated for bilateral quadriceps
contracture. Conventional treatments including surgery, dynamic flexion apparatus
and physical therapy along with analgesics and non-steroidal anti-inflammatory
drugs resulted in temporary clinical improvement that was relapsing. The
initiation of supplementary corticosteroid treatment with prednisolone coincided
with an immediate and sustained clinical improvement and long-term resolution.
RELEVANCE AND NOVEL INFORMATION: Successful treatment of bilateral quadriceps
contracture has not previously been reported in a cat. Quadriceps contracture
remains a challenging condition to treat with some cases unresponsive to therapy.
Systemic prednisolone treatment appeared to be of benefit in the management of
this case and may have a role in some cats where muscle contracture appears
relapsing in nature. Further prospective investigations in cats with muscle
contracture, including muscle biopsies of affected cats, are warranted.
PMID- 28491457
TI - A case of acute acquired obstructive hydrocephalus in a cat with suspected
ischaemic cerebellar infarct.
AB - CASE SUMMARY: A case of acquired acute obstructive hydrocephalus that developed
as a complication of an ischaemic infarct in the vascular territory of the
rostral cerebellar artery is described in an adult domestic shorthair cat. The
clinical findings, diagnostic investigations, treatment and prognosis are
reported. MRI findings are described in detail. RELEVANCE AND NOVEL INFORMATION:
This is the first report of obstructive hydrocephalus as a complication of an
ischaemic infarct in the region of the rostral cerebellar artery in a cat. MRI
findings are described in detail with regard to the recognition of the early
signs of obstructive hydrocephalus. A brief review of the literature is included,
as this complication has been frequently reported in humans.
PMID- 28491458
TI - Caecocolic intussusception associated with a caecal polyp and concurrent
hepatocellular carcinoma in a cat.
AB - CASE SUMMARY: A 17-year-old female neutered domestic shorthair cat presented for
several days of reduced faecal volume and a rectal prolapse. Physical examination
revealed a 2 cm rectal prolapse, hepatomegaly and a low body condition score of
3/9. Haematology and biochemistry revealed a mild non-regenerative anaemia
(haematocrit 24.5%; reference interval [RI] 30.3-52.3%), a mild mature
neutrophilia (16.21 * 109/l; RI 1.48-10.29 * 109/l) and a mild increase in
alanine aminotransferase activity (222 IU/l; RI 12-130 IU/l). Abdominal
radiographs identified hepatomegaly. The rectal prolapse was reduced under
general anaesthesia. Abdominal ultrasound identified a caecocolic intussusception
and a large hepatic mass. Thoracic radiographs were unremarkable. Hepatic fine
needle aspirate cytology revealed well-differentiated hepatocytes. A typhlectomy
was performed and the quadrate liver lobe, with mass, was resected. Gross
examination of the caecum identified a focal polyp; histopathology showed
moderate plasmacytic-lymphocytic typhlitis and reactive mucosal-associated
lymphoid tissue. The hepatic mass was diagnosed as a well-differentiated
hepatocellular carcinoma. Six weeks postoperatively the cat had gained 0.5 kg,
had an improved body condition score of 5/9 and resolution of clinical signs. The
cat died acutely 1 year later from an unknown cause. RELEVANCE AND NOVEL
INFORMATION: Caecocolic intussusception is rare in cats and uncommon in dogs.
This is the third report in a cat and the first associated with a caecal polyp.
As reported in dogs, the outcome following surgery was good. Hepatocellular
carcinoma is a rarely reported feline neoplasm, which may have a good prognosis
with surgical resection.
PMID- 28491459
TI - On Your Feet to Earn Your Seat: pilot RCT of a theory-based sedentary behaviour
reduction intervention for older adults.
AB - BACKGROUND: Of all age groups, older adults spend most of the time sitting and
are least physically active. This sequential, mixed-methods feasibility study
used a randomised controlled trial design to assess methods for trialling a habit
based intervention to displace older adults' sedentary behaviour with light
activity and explore impact on behavioural outcomes. METHODS: Eligibility
criteria were age 60-74 years, retired, and >=6 h/day leisure sitting. Data were
collected across four sites in England. The intervention comprised a booklet
outlining 15 'tips' for disrupting sedentary habits and integrating activity
habits into normally inactive settings, and eight weekly self-monitoring sheets.
The control was a non-habit-based factsheet promoting activity and sedentary
reduction. A computer-generated 1:1 block-randomisation schedule was used, with
participants blinded to allocation. Participants self-reported sedentary
behaviour (two indices), sedentary habit, physical activity (walking, moderate,
vigorous activity) and activity habit, at pre-treatment baseline, 8- and 12-week
follow-ups and were interviewed at 12 weeks. Primary feasibility outcomes were
attrition, adverse events and intervention adherence. The secondary outcome was
behavioural change. RESULTS: Of 104 participants consented, 103 were randomised
(intervention N = 52, control N = 51). Of 98 receiving allocated treatment, 91
(93%; intervention N = 45; control N = 46) completed the trial. One related
adverse event was reported in the intervention group. Mean per-tip adherence
across 7 weeks was >=50% for 9/15 tips. Qualitative data suggested acceptability
of procedures, and, particularly among intervention recipients, the allocated
treatment. Both groups appeared to reduce sedentary behaviour and increase their
physical activity, but there were no apparent differences between groups in the
extent of change. CONCLUSIONS: Trial methods were acceptable and feasible, but
the intervention conferred no apparent advantage over control, though it was not
trialled among the most sedentary and inactive population for whom it was
developed. Further development of the intervention may be necessary prior to a
large-scale definitive trial. One possible refinement would combine elements of
the intervention with an informational approach to enhance effectiveness. TRIAL
REGISTRATION: ISRCTN47901994 (registration date: 16th January 2014; trial end
date 30th April 2015).
PMID- 28491460
TI - Correlation between retinal function and microstructural foveal changes in
intermediate age related macular degeneration.
AB - PURPOSE: To assess foveal microstructural changes influencing retinal sensitivity
(RS) and fixation stability using microperimeter MP-1 in intermediate age-related
macular degeneration (AMD). METHODS: In this cross-sectional study, 22 eyes of 22
patients (mean age: 75 +/- 9.02 years) with intermediate AMD were enrolled.
Retinal sensitivity and bivariate contour ellipse area (BCEA) were obtained by
microperimetry MP-1 (Humphrey 10-2 68-loci grid) under mesopic conditions. Drusen
type, drusenoid pigment epithelial detachment, hyperreflective foci (HF),
integrity of external limiting membrane (ELM), inner ellipsoid zone (ISel),
RPE/Bruch's membrane complex (RPE/B) and subfoveal choroidal thickness were
analyzed in the foveal region and compared with RS and BCEA. Spearman's rank
correlation coefficient was used to evaluate the relationship between variables.
Logistic regression analysis was also used to assess morphological predictor
influencing RS or BCEA. RESULTS: RS was strongly and inversely related with the
presence of HF (r = -0.66, P = 0.001), integrity of ELM (r = -0.70, P < 0.001),
ellipsoid zone (r = -0.45, P = 0.03). Instead, BCEA is positively related to the
ellipsoid zone integrity (r = 0.45, P = 0.03). Logistic regression analysis
confirmed that disruption of ISel influenced fixation stability (ExpB: 9.69, P =
0.04) but not RS. Instead, the presence of HF and disruption of ELM predicted RS
reduction (ExpB: 0.55, P = 0.02 and ExpB: 0.29, P = 0.04, respectively).
CONCLUSIONS: The integrity of ELM and the presence of HF are both predictors of
RS. The ELM status may be considered a new biomarker of retinal function together
with HF. Instead, the integrity of ISel band seems to be a more selective
predictor of BCEA than RS.
PMID- 28491461
TI - Imaging findings of solitary uterine granulocytic sarcoma.
AB - A 29-year old woman with a history of vaginal bleeding was referred to our
hospital. Transvaginal ultrasonography revealed a hypervascular cervical mass and
malignancy was suspected. Computed tomography (CT), magnetic resonance imaging,
and 18-F-fluorodeoxyglucose positron emission tomography/CT were performed. She
was finally diagnosed with granulocytic sarcoma based on pathological
examination.
PMID- 28491462
TI - Understanding microstructure of the brain by comparison of neurite orientation
dispersion and density imaging (NODDI) with transparent mouse brain.
AB - BACKGROUND: Neurite orientation dispersion and density imaging (NODDI) is a
diffusion magnetic resonance imaging (MRI) technique with the potential to
visualize the microstructure of the brain. Revolutionary histological methods to
render the mouse brain transparent have recently been developed, but verification
of NODDI by these methods has not been reported. PURPOSE: To confirm the
concordance of NODDI with histology in terms of density and orientation
dispersion of neurites of the brain. MATERIAL AND METHODS: Whole brain diffusion
MRI of a thy-1 yellow fluorescent protein mouse was acquired with a 7-T MRI
scanner, after which transparent brain sections were created from the same mouse.
NODDI parameters calculated from the MR images, including the intracellular
volume fraction (Vic) and the orientation dispersion index (ODI), were compared
with histological findings. Neurite density, Vic, and ODI were compared between
areas of the anterior commissure and the hippocampus containing crossing fibers
(crossing areas) and parallel fibers (parallel areas), and the correlation
between fiber density and Vic was assessed. RESULTS: The ODI was significantly
higher in the crossing area compared to the parallel area in both the anterior
commissure and the hippocampus (P = 0.0247, P = 0.00022, respectively). Neurite
density showed a similar tendency, but was significantly different only in the
hippocampus (P = 7.91E-07). There was no significant correlation between neurite
density and Vic. CONCLUSION: NODDI was verified by histology for quantification
of the orientation dispersion of neurites. These results indicate that the ODI is
a suitable index for understanding the microstructure of the brain in vivo.
PMID- 28491463
TI - "Pro-dopamine regulation (KB220ZTM)" as a long-term therapeutic modality to
overcome reduced resting state dopamine tone in opiate/opioid epidemic in
America.
AB - Since it is known that relapse, morality, and hospitalizations have been tied to
the presence of the Dopamine D2 Receptor A1 allele, as one example, and carriers
of this gene variant have a proclivity to favor amino-acid therapy, it seems
intuitive that the incorporation of modalities to provide a balance and or
restoration of hypodopaminergia should be considered as a front-line tactic to
overcome the current American opiate/opioid epidemic, saving millions from death
and unwanted locked-in-addiction. If we continue down the prim road path of
fighting addiction to narcotics with narcotics, we are doomed to fail. This
lesson can also have global interest.
PMID- 28491464
TI - Decreasing Aerosol Loading in the North American Monsoon Region.
AB - We examine the spatio-temporal variability of aerosol loading in the recent
decade (2005-2014) over the North American Monsoon (NAM) region. Emerging
patterns are characterized using aerosol optical depth (AOD) retrievals from the
NASA Terra/Moderate Resolution Imaging Spectroradiometer (MODIS) instrument along
with a suite of satellite retrievals of atmospheric and land-surface properties.
We selected 20 aerosol hotspots and classified them into fire, anthropogenic,
dust, and NAM alley clusters based on the dominant driver influencing aerosol
variability. We then analyzed multivariate statistics of associated anomalies
during pre-, monsoon, and post-monsoon periods. Our results show a decrease in
aerosol loading for the entire NAM region, confirming previous reports of a
declining AOD trend over the continental United States. This is evident during
pre-monsoon and monsoon for fire and anthropogenic clusters, which are associated
with a decrease in the lower and upper quartile of fire counts and carbon
monoxide, respectively. The overall pattern is obfuscated in the NAM alley,
especially during monsoon and post-monsoon seasons. While the NAM alley is mostly
affected by monsoon precipitation, the frequent occurrence of dust storms in the
area modulates this trend. We find that aerosol loading in the dust cluster is
associated with observed vegetation index and has only slightly decreased in the
recent decade.
PMID- 28491465
TI - The potential scientist's dilemma: How the Masculinization of Science Shapes
Friendships and Science Job Preferences.
AB - In the United States, girls and boys have similar science achievement, yet fewer
girls aspire to science careers than boys. This paradox emerges in middle school,
when peers begin to play a stronger role in shaping adolescent identities. We use
complete network data from a single middle school and theories of gender,
identity, and social distance to explore how friendship patterns might influence
this gender and science paradox. Three patterns highlight the social dimensions
of gendered science persistence: (1) boys and girls do not differ in self
perceived science potential and science career aspirations; (2) consistent with
gender-based norms, both middle school boys and girls report that the majority of
their female friends are not science kinds of people; and (3) youth with gender
inconsistent science aspirations are more likely to be friends with each other
than youth with gender normative science aspirations. Together, this evidence
suggests that friendship dynamics contribute to gendered patterns in science
career aspirations.
PMID- 28491466
TI - Changes in Retinal Function and Cellular Remodeling Following Experimental
Retinal Detachment in a Rabbit Model.
AB - Purpose. To explore functional electroretinographic (ERG) changes and associated
cellular remodeling following experimental retinal detachment in a rabbit model.
Methods. Retinal detachment was created in ten rabbits by injecting 0.1 ml
balanced salt solution under the retina. Fundus imaging was performed 0, 3, 7,
14, and 21 days postoperatively. ERGs were recorded pre- and 7 and 21 days
postoperatively. Eyes were harvested on day 21 and evaluated
immunohistochemically (IHC) for remodeling of second- and third-order neurons.
Results. Retinal reattachment occurred within two weeks following surgery. No
attenuation was observed in the photopic or scotopic a- and b-waves. A secondary
wavefront on the descending slope of the scotopic b-wave was the only ERG result
that was attenuated in detached retinas. IHC demonstrated anatomical changes in
both ON and OFF bipolar cells. Bassoon staining was observed in the remodeled
dendrites. Amacrine and horizontal cells did not alter, but Muller cells were
clearly reactive with marked extension. Conclusion. Retinal detachment and
reattachment were associated with functional and anatomical changes. Exploring
the significance of the secondary scotopic wavefront and its association with the
remodeling of 2nd- and 3rd-order neurons will shade more light on functional
changes and recovery of the retina.
PMID- 28491467
TI - Association between Asymptomatic Unilateral Internal Carotid Artery Stenosis and
Electrophysiological Function of the Retina and Optic Nerve.
AB - Purpose. This study was designed to assess retinal and optic nerve bioelectrical
function in patients with unilateral asymptomatic but hemodynamically significant
internal carotid artery stenosis (ICAS). Methods. Forty-two subjects with a
diagnosis of unilateral ICAS and 34 controls were analyzed. Full-field
electroretinogram (ERG), pattern electroretinogram (PERG), and pattern visual
evoked potentials, as well as optical coherence tomography and ophthalmological
examination, were performed. Data analysis included eyes ipsilateral to ICAS
(EIS) and eyes contralateral to ICAS (ECS). Results. Intraocular pressure was
significantly decreased in EIS and ECS compared to that in the controls. In the
macula, both the cube average thickness and cube volume values were significantly
reduced both in EIS and ECS compared to those in the controls. Similarly, PERG
P50 and N95 wave amplitudes were significantly smaller in EIS and ECS compared to
those in the controls. The ERG rod b-wave and rod-cone a-wave amplitudes were
decreased, and implicit times were significantly prolonged, whereas the OP wave
index was reduced in EIS compared to that in the controls. No differences in IOP,
OCT, or ERG and PERG parameters were identified between EIS and ECS. Conclusions.
Our study demonstrated that retinal bioelectrical function is negatively affected
by ICAS despite the absence of objective clinical signs and symptoms of ocular
ischemia.
PMID- 28491469
TI - Novel Diagnostic and Therapeutic Methods in Ocular Surface and Corneal Diseases.
PMID- 28491468
TI - Recurrence of Retinopathy of Prematurity in Zone II Stage 3+ after Ranibizumab
Treatment: A Retrospective Study.
AB - Objective. To determine the prevalence and risk factors for the recurrence of
retinopathy of prematurity (ROP) in Zone II Stage 3+ after ranibizumab treatment.
Methods. This was a retrospective, nonrandomized, noncontrolled study that
excluded Zone I and aggressive posterior ROP (APROP) cases. Infants who developed
Zone II Stage 3 ROP with plus disease and underwent initial intravitreal
injection of ranibizumab (IVR) were recruited. Patients were divided into 2
groups based on the outcome after initial ranibizumab treatment: recurrence of
ROP or favorable outcome. Data was collected and analyzed by SPSS 16.0. Results.
Forty-two patients were included, and 80 eyes with Zone II Stage 3+ were
subjected to IVR treatment. Eleven of 42 patients (26.2%, 18 eyes) had a
recurrence of ROP after the initial treatment. On univariate analysis, preretinal
hemorrhage before treatment was significantly different between the two groups (P
= 0.000). Multivariate analysis found that preretinal hemorrhage before treatment
was the only factor associated with the recurrence of ROP in our study (P =
0.004). Conclusions. The recurrence rate of ROP in Zone II Stage 3+ after initial
ranibizumab treatment was notable and preretinal hemorrhage before treatment was
associated with the recurrence of ROP in our study.
PMID- 28491470
TI - Effect of Active and Passive Smoking on Retinal Nerve Fibre Layer and Ganglion
Cell Complex.
AB - Aim. To evaluate the possible structural and functional changes in the retinal
nerve fibre layer (RNFL) and the ganglion cell complex (GCC) of chronic smokers
and compare them with those of passive healthy smokers using spectral domain
optical coherence tomography (SD-OCT) and pattern electroretinogram (PERG).
Materials and Methods. We include 80 active chronic smokers and 80 age- and sex
matched healthy passive smokers. After a full ophthalmological examination, SD
OCT and PERG were tested for all participants. Urinary levels of cotinine and
creatinine with subsequent calculation of the cotinine creatinine ratio (CCR).
Results. Inferior and superior quadrants of RNFL were thinner in group I, but
nasal and temporal quadrants did not show significant difference between the
groups. There were no significant differences of GCC values between the two
groups. There was no significant difference of PERG-P50 amplitude and latency;
however, PERG-N95 showed significant difference between the two groups. Multiple
regression analyses demonstrated that the number of cigarettes/day, urinary
cotinine, and PERG-N95 amplitude are the most important determinants for both
superior and inferior RNFL thicknesses. Conclusion. RNFL thickness decreases in
chronic, healthy, heavy cigarette smokers, and this thinning is related to the
number of cigarettes/day, urinary cotinine, and PERG-N95 latency and amplitude.
PMID- 28491471
TI - A Novel Three-Dimensional Vector Analysis of Axial Globe Position in Thyroid Eye
Disease.
AB - Purpose. To define a three-dimensional (3D) vector method to describe the axial
globe position in thyroid eye disease (TED). Methods. CT data from 59 patients
with TED were collected and 3D images were reconstructed. A reference coordinate
system was established, and the coordinates of the corneal apex and the eyeball
center were calculated to obtain the globe vector [Formula: see text]. The
measurement reliability was evaluated. The parameters of [Formula: see text] were
analyzed and compared with the results of two-dimensional (2D) CT measurement,
Hertel exophthalmometry, and strabismus tests. Results. The reliability of
[Formula: see text] measurement was excellent. The difference between [Formula:
see text] and 2D CT measurement was significant (p = 0.003), and [Formula: see
text] was more consistent with Hertel exophthalmometry than with 2D CT
measurement (p < 0.001). There was no significant difference between [Formula:
see text] and Hirschberg test, and a strong correlation was found between
[Formula: see text] and synoptophore test. When one eye had a larger deviation
angle than its fellow, its corneal apex shifted in the corresponding direction,
but the shift of the eyeball center was not significant. The parameters of
[Formula: see text] were almost perfectly consistent with the geometrical
equation. Conclusions. The establishment of a 3D globe vector is feasible and
reliable, and it could provide more information in the axial globe position.
PMID- 28491473
TI - Clinical Analysis of Ocular Parameters Contributing to Intraoperative Pain during
Standard Phacoemulsification.
AB - Purpose. To study the correlation between ocular parameters and subjective pain
that patients perceived during phacoemulsification. Methods. Medical records of
142 patients who underwent standard phacoemulsification under topical anesthesia
between March and August 2016 were retrospectively reviewed. The pain during
phacoemulsification and 1 h after surgery was assessed and compared using a
visual analog scale. In addition, demographic data, preoperative biometric
parameters, and intraoperative surgical parameters were recorded. Results. Mean
age of patients was 67.49 +/- 12.50 years. The mean pain score was 2.26 +/- 0.85
during phacoemulsification and 0.40 +/- 0.69 postoperatively. Intraoperative pain
was significantly associated with higher preoperative intraocular pressure (beta
= 0.220, P = 0.016), greater anterior chamber depth (beta = 0.210, P = 0.028),
and greater axial length (beta = 0.181, P = 0.043). Conclusions. To reduce the
subjective pain when patients have high preoperative intraocular pressure, large
anterior chamber depth, or great axial length, supplementary procedures may be
required.
PMID- 28491472
TI - The Effect of Corneal Refractive Surgery on Glaucoma.
AB - Laser-assisted refractive procedures have become very popular in the last two
decades. As a result, a "generation" of patients with altered corneal properties
is emerging. These patients will require both cataract extraction and glaucoma
follow-up in the future. Since the glaucoma examination largely depends on the
corneal properties, the reshaped postrefractive surgery cornea poses a challenge
in the diagnosis, follow-up, and management of the glaucomatous patient. In order
to overcome this problem, every patient who is planned to undergo corneal
refractive surgery must have a thorough glaucoma examination in order for the
ophthalmologist to be able to monitor their patients for possible glaucoma
development and/or progression. Some examinations such as tonometry are largely
affected by the corneal properties, while others such as the evaluation of the
structures of the posterior pole remain unaffected. However, the new imaging
modalities of the anterior segment in combination with the most recent advances
in tonometry can accurately assess the risk for glaucoma and the need for
treatment.
PMID- 28491474
TI - The Role of Race and Gender in Nutrition Habits and Self-Efficacy: Results from
the Young Adult Weight Loss Study.
AB - Overweight and obesity are a massive public health problem and young adults are
at high risk for gaining weight once they enter a college. This study sought to
examine gender and race as they relate to nutrition habits and self-efficacy in a
population of diverse young adults from the Young Adult Weight Loss Study.
Participants (N = 62) were 29% males, 38.7% white, 33.8% Asian, and 12.9% African
American. Males had lower self-efficacy for healthy eating (mean score = 92.5, SD
= 17.1) compared to females (mean = 102.3, SD = 13.7, p = 0.02). Males had higher
consumption of sodium compared to females (4308 versus 3239 milligrams/day, p =
0.01). There were no significant differences across racial subgroups in self
efficacy for healthy eating (p = 0.67) or self-efficacy for exercise (p = 0.61).
Higher self-efficacy scores for healthy eating were significantly associated with
less total sodium (r = -0.37, p = 0.007), greater fruit consumption, and less
saturated fat. Our results indicate that weight loss interventions should be
individualized and that there may be specific areas to target that are different
for men and women. Additional larger studies should be conducted to confirm if
racial differences exist across nutrition habits and self-efficacy and to confirm
gender differences noted in this study.
PMID- 28491475
TI - Referral Patterns and Diagnostic Yield of Lung Scintigraphy in the Diagnosis of
Acute Pulmonary Embolism.
AB - Introduction. The purpose of this study is to assess referral patterns and the
yield of ventilation-perfusion (V/Q) scintigraphy in patients referred for acute
pulmonary embolism (PE). Methods. We retrospectively reviewed the charts of all
patients who underwent V/Q studies between April 1, 2008, and March 31, 2010.
Patients were subdivided into 4 groups based on their referral source: emergency
department (ED), hospital inpatient ward, outpatient thrombosis clinic, and all
other outpatient sources. Results. A total of 1008 patients underwent V/Q
scintigraphy to exclude acute PE. The number of ED, inpatient, thrombosis clinic,
and outpatient studies was 43 (4.3%), 288 (28.6%), 351 (34.8%), and 326 (32.3%).
Proportion of patients with contrast contraindication varied significantly among
the different groups. Of the 1,008 studies, 331 (32.8%) were interpreted as
normal, 408 (40.5%) as low, 158 (15.7%) as intermediate, and 111 (11.0%) as high
probability for PE. 68 (6.7%) patients underwent CTPA within 2 weeks following
V/Q. Conclusion. The rate of nondiagnostic studies is lower than that reported in
previously published data, with a relatively low rate of intermediate probability
studies. Only a small fraction of patients undergoing a V/Q scan will require a
CTPA.
PMID- 28491476
TI - Increased Intracranial Pressure in the Setting of Enterovirus and Other Viral
Meningitides.
AB - Increased intracranial pressure due to viral meningitis has not been widely
discussed in the literature, although associations with Varicella and rarely
Enterovirus have been described. Patients with increased intracranial pressure
and cerebrospinal fluid analysis suggestive of a viral process are sometimes
classified as having atypical idiopathic intracranial hypertension (IIH).
However, a diagnosis of IIH requires normal cerebrospinal fluid, and therefore in
these cases an infection with secondary intracranial hypertension may be a more
likely diagnosis. Here seven patients are presented with elevated intracranial
pressure and cerebrospinal fluid suggestive of viral or aseptic meningitis. Of
these, 1 had Enterovirus and the remainder were diagnosed with nonspecific viral
meningitis. These data suggest that viral meningitis may be associated with
elevated intracranial pressure more often than is commonly recognized.
Enterovirus has previously been associated with increased intracranial pressure
only in rare case reports.
PMID- 28491477
TI - The Effect of Diabetic Peripheral Neuropathy on Ground Reaction Forces during
Straight Walking in Stroke Survivors.
AB - Purpose. The aim of this present study was to investigate the ground reaction
forces (GRFs) alterations in stroke survivors with diabetic peripheral neuropathy
(DPN). Methods. Ten stroke survivors with DPN, 10 stroke survivors without DPN,
and 10 healthy controls with matched body weight between groups participated in
this case-control cross-sectional study. Three-dimensional GRFs (anterior
posterior, medial-lateral, and vertical) were collected at a comfortable walking
speed using the Nexus Vicon motion analysis system and force plate. The Kruskal
Wallis test was used to analyze GRFs parameters. Results. We found significant
alterations of medial-lateral forces of the nonparetic side and vertical forces
of the paretic side in stroke survivors with DPN compared to stroke survivors
without DPN and healthy controls. In addition, there were smaller braking and
lower propulsion peak in anterior-posterior forces, smaller magnitude of medial
lateral forces, and lower first and second peak of vertical forces in stroke
survivors with DPN compared to stroke survivors without DPN and healthy controls.
Conclusion. The study findings identified that GRFs were affected in stroke
survivors with DPN on both the paretic and the nonparetic sides. Further
investigations are warranted to explore the impact of DPN on the kinematics and
muscle activity related to the gait performance in stroke survivors with DPN.
PMID- 28491478
TI - Rehabilitation Treatment and Progress of Traumatic Brain Injury Dysfunction.
AB - Traumatic brain injury (TBI) is a major cause of chronic disability. Worldwide,
it is the leading cause of disability in the under 40s. Behavioral problems,
mood, cognition, particularly memory, attention, and executive function are
commonly impaired by TBI. Spending to assist, TBI survivors with disabilities are
estimated to be costly per year. Such impaired functional outcomes following TBI
can be improved via various rehabilitative approaches. The objective of the
present paper is to review the current rehabilitation treatment of traumatic
brain injury in adults.
PMID- 28491479
TI - Therapeutic Potentials of Synapses after Traumatic Brain Injury: A Comprehensive
Review.
AB - Massive studies have focused on the understanding of the pathobiology of cellular
and molecular changes and injury mechanisms after traumatic brain injury (TBI),
but very few studies have specially discussed the role of synapses in the context
of TBI. This paper specifically highlights the role and therapeutic potentials of
synapses after TBI. First, we review and conclude how synapses interact with
constant structural, metabolic, neuroendocrine, and inflammatory mechanisms after
TBI. Second, we briefly describe several key synaptic proteins involved in
neuroplasticity, which may be novel neuronal targets for specific intervention.
Third, we address therapeutic interventions in association with synapses after
TBI. Finally, we concisely discuss the study gaps in the synapses after TBI, in
hopes that this would provide more insights for future studies. Synapses play an
important role in TBI; while the understandings on the synaptic participation in
the treatments and prognosis of TBI are lacking, more studies in this area are
warranted.
PMID- 28491481
TI - Retinal Artery Occlusion Secondary to Buerger's Disease (Thromboangiitis
Obliterans).
AB - Purpose. To report a case report of one patient suffering from retinal artery
occlusion secondary to Buerger's disease, in order to raise awareness to this
etiology in the differential diagnosis of retinal artery occlusion. Methods. A
retrospective case report of a patient with retinal artery occlusion secondary to
Buerger's disease. Data retrieved from the medical records included exposure,
complaints, visual acuity, clinical findings and imaging, laboratory assessment,
treatment, disease course, and visual outcome. Results. Diagnosis of retinal
artery occlusion secondary to Buerger's disease was established based on ruling
out other causes of retinal artery occlusion. Inflammatory retinal vascular
disease, permanent vision loss, and macular atrophy were shown in this case.
Conclusion. The very first case of central retinal artery occlusion (CRAO) in a
64-year-old male patient with Buerger's disease. Although diagnosing CRAO based
on both fundoscopic and fluorescein angiographic findings is not difficult,
revealing underlying condition of CRAO occasionally could be challenging.
PMID- 28491480
TI - New Treatment Strategies of Depression: Based on Mechanisms Related to
Neuroplasticity.
AB - Major depressive disorder is a severe and complex mental disorder. Impaired
neurotransmission and disrupted signalling pathways may influence
neuroplasticity, which is involved in the brain dysfunction in depression.
Traditional neurobiological theories of depression, such as monoamine hypothesis,
cannot fully explain the whole picture of depressive disorders. In this review,
we discussed new treatment directions of depression, including modulation of
glutamatergic system and noninvasive brain stimulation. Dysfunction of
glutamatergic neurotransmission plays an important role in the pathophysiology of
depression. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has
rapid and lasting antidepressive effects in previous studies. In addition to
ketamine, other glutamatergic modulators, such as sarcosine, also show potential
antidepressant effect in animal models or clinical trials. Noninvasive brain
stimulation is another new treatment strategy beyond pharmacotherapy. Growing
evidence has demonstrated that superficial brain stimulations, such as
transcranial magnetic stimulation, transcranial direct current stimulation,
cranial electrotherapy stimulation, and magnetic seizure therapy, can improve
depressive symptoms. The antidepressive effect of these brain stimulations may be
through modulating neuroplasticity. In conclusion, drugs that modulate
neurotransmission via NMDA receptor and noninvasive brain stimulation may provide
new directions of treatment for depression. Furthermore, exploring the underlying
mechanisms will help in developing novel therapies for depression in the future.
PMID- 28491482
TI - Long-Term Prophylaxis and Pharmacokinetic Evaluation of Intramuscular Nano- and
Microparticle Decoquinate in Mice Infected with P. berghei Sporozoites.
AB - Decoquinate nanoparticle and microparticle suspended in an oily vehicle to retard
drug release are evaluated for long-term malaria prophylaxis. Pharmacokinetic
studies in normal animals and antimalarial efficacy in liver stage malaria mice
were conducted at various single intramuscular-decoquinate doses for 2, 4, 6, or
8 weeks prior to infection with P. berghei sporozoites. The liver stage efficacy
evaluation was monitored by using an in vivo imaging system. Full causal
prophylaxis was shown in mice with a single intramuscular dose at 120 mg/kg of
nanoparticle decoquinate (0.43 MUm) for 2-3 weeks and with microparticle
decoquinate (8.31 MUm) injected 8 weeks earlier than inoculation. The time above
MIC of 1,375 hr observed with the microparticle formulation provided a 2.2-fold
longer drug exposure than with the nanoparticle formulation (624 hr). The
prophylactic effect of the microparticle formulation observed in mice was shown
to be 3-4 times longer than the nanoparticle decoquinate formulation.
PMID- 28491484
TI - Valvular Hemolysis Masquerading as Prosthetic Valve Stenosis.
AB - The evaluation of prosthetic valves can provide a unique challenge, and a
thoughtful approach is required. High output states like anemia should be kept in
the differential when evaluating elevated gradients across prosthetic valves. We
present the case of a 69-year-old man with a Starr-Edwards prosthetic aortic
valve who presented with symptoms of congestive heart failure and high
transvalvular pressure gradients. These symptoms indicate a potential prosthetic
valve stenosis. His laboratory evaluation results were consistent with valve
related hemolysis. Resolving his anemia led to a resolution of the symptoms and
lowered the pressure gradient on follow-up.
PMID- 28491483
TI - Twelve weeks of dance exergaming in overweight and obese adolescent girls:
Transfer effects on physical activity, screen time, and self-efficacy.
AB - BACKGROUND: Given the low levels of physical activity (PA) among adolescent girls
in the US, there is a need to identify tools to motivate increased PA. Although
there is limited evidence that adolescents transfer PA from one context to
another context, exergames (i.e., video games that require gross motor activity)
may act as a gateway to promote overall PA outside of game play. The purpose of
this study was to examine potential transfer effects (i.e., influences on
external behaviors and psychological constructs) of a 12-week exergaming
intervention on adolescent girls' PA, screen-time, and self-efficacy towards PA,
as well as the intrinsic motivation of exergaming. METHODS: Participants were 37
girls aged 14-18 years (65% African American, 35% White) who were overweight or
obese (body mass index >= 85th percentile) and were recruited from the community
via school, physicians, news media, and social media sites. Adolescents were
randomly assigned to a 12-week group exergaming intervention (thirty-six 60 min
sessions of group-based dance exergaming in a research laboratory using Kinect
for Xbox 360) or to a no-treatment control group. Outcome variables included
objectively measured PA (total) and self-reported leisure-time PA (discretionary
time only) 1-week before vs. 1-week after the intervention; selected type and
intensity of PA when placed in a gym setting for 30 min ("cardio free choice");
screen-time; self-efficacy towards PA; and intrinsic motivation towards
exergaming. RESULTS: Attendance to the exergaming sessions was high (80%).
Compared to the control group, the intervention group self-reported an increase
in PA (p = 0.035) and fewer hours watching TV/videos (p = 0.01) after the
intervention, but there were no significant differences in sedentary, light,
moderate, or vigorous PA measured by accelerometry. The intervention group
significantly improved self-efficacy towards PA (p = 0.028). The intervention
group highly rated intrinsic motivation towards exergaming. CONCLUSION: Twelve
weeks of exergaming was associated with positive impacts on adolescent girls'
self-reported PA, television viewing, self-efficacy, and intrinsic motivation.
Future research is warranted to leverage exergames as an enjoyable, motivating,
and effective PA tool.
PMID- 28491485
TI - Cardiovascular Risk of Nonsteroidal Anti-Inflammatory Drugs: An Under-Recognized
Public Health Issue.
AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) are drugs with analgesic, anti
inflammatory, and antipyretic activity. Their effect is achieved by the reduction
in synthesis of prostanoids. Inhibition of prostanoids is responsible for a
substantial risk of adverse effects. The risk of side effects affecting the
gastrointestinal tract and kidneys has long been known. The possibilities of
blood pressure elevation and the development of congestive heart failure are also
widely recognized. Increased incidence of acute myocardial infarction in clinical
trials with rofecoxib drew attention to the potential cardiotoxicity of selective
cyclooxygenase-2 inhibitors, and similarly, concerns have been raised regarding
the cardiovascular safety of non-selective NSAIDs. The safety of NSAIDs with
regards to cardiovascular events has been studied in recent years in a large
number of retrospective and prospective clinical studies and meta-analyses. The
results indicate that cardiotoxicity is a class effect, but the magnitude of the
risk is widely variable between individual NSAID drugs. This article aims to
summarize the available data on the risk of adverse cardiovascular events with
NSAIDs, the clinical impact of these events and possible underlying mechanisms.
PMID- 28491486
TI - CREST Calcinosis Affecting the Lumbar and Cervical Spine and the Use of Minimally
Invasive Surgery.
AB - Calcinosis in CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility,
sclerodactyly, and telangiectasia) syndrome can affect the spinal and paraspinal
areas. We present the first case to our knowledge where a CREST syndrome patient
required surgery for spinal calcinosis in both the cervical and lumbar areas. A
66-year-old female with a history of CREST syndrome presented with right-sided
lower extremity radicular pain. A computed tomography (CT) scan showed bilateral
lumbar masses (5.8 cm on the right, 3.8 cm on the left) that projected into the
foramina and into the spinal canal. The patient underwent minimally invasive
bilateral surgical resection of the paraspinal masses, posterior decompressive
laminectomy, posterior interbody, and posterolateral fusion. The specimen was
consistent with the calcinosis of CREST syndrome. The patient's lumbar symptoms
were relieved, however, two years later she presented with right radicular arm
pain. A CT scan revealed a large lobulated benign tumor-like lesion on the left
at C6-C7 encroaching upon the neural foramen and a large right lobulated lesion
encroaching into the neural foramen with severe compression of the neural foramen
at the C7-T1 level and extension into the canal, with anterior and posterior
subluxation present throughout the cervical spine. Surgery was performed, which
involved cervical mass resections, posterior spinal cord decompression,
reconstruction, and fusion. The patient did well and has been symptom-free since
her surgery. Calcinosis of the spine is a known entity that can cause morbidity
in patients with CREST syndrome. Minimal invasive surgical approaches are
effective and can be considered for some of these patients.
PMID- 28491488
TI - Dog attachment and perceived social support in overweight/obese and healthy
weight children.
AB - The development of effective and sustainable interventions to treat childhood
obesity remains both a priority and a challenge. Previous studies support that
dogs provide social support in overweight adults in obesity interventions, but
the child-dog relationship is not as well understood. The goal of the study was
to examine the child-dog relationship among children to inform novel childhood
obesity interventions including dogs. A cross-sectional study was conducted in
the Living Laboratory(r) at the Museum of Science, Boston in 2015. Children aged
8-13, with a dog in the household, answered surveys on pet attachment (Pet
Relationship Scale), perceived social support from parents and close friends
(Child and Adolescent Social Support Scale), and had a height and weight
measurement taken for calculation of body mass index percentile. Overweight and
obese children (>= 85th body mass index percentile) had greater mean attachment
score to their dog and less mean perceived social support from their parents and
friends combined compared to healthy weight children (73.1 +/- 5.6 vs. 68.5 +/-
7.2, p = 0.037; 110.5 +/- 13.5 vs. 122.9 +/- 14.8, p = 0.015, respectively; n =
43). In conclusions, children who are overweight/obese report greater mean dog
attachment and lower mean perceived social support, supporting the concept that
pet dogs are considered part of overweight/obese children's social support
networks. Future studies are warranted to evaluate the impact of including pet
dogs as additional health support in child obesity interventions.
PMID- 28491490
TI - Rapid emergence of FKS mutations in Candida glabrata isolates in a peritoneal
candidiasis.
AB - We report a rapid acquisition of echinocandin resistance after 12 days of
micafungin treatment, without prior exposure, in a patient with peritoneal
candidiasis due to C. glabrata. Isolates recovered before and after treatment
were compared by multilocus sequence typing. Results of antifungal susceptibility
testing and FKS mutations were reported. The interest of repeating antifungal
susceptibility testing for echinocandin molecules during the treatment is
discussed and a strategy to research FKS mutations proposed.
PMID- 28491489
TI - The social context moderates the relationship between neighborhood safety and
adolescents' activities.
AB - Studies of neighborhood safety and physical activity have typically neglected to
consider the youth's peer context as a modifier of these relationships. This
study fills this gap in testing the independent and interactive effects of
perceived neighborhood safety and time spent with friends and peers on young
adolescents' physical activity and sedentary behavior. Participants (N = 80; ages
13-17) completed the Pedestrian/Traffic Safety and Crime Safety subscales of the
adolescent version of the Neighborhood Environment Walkability Scale (NEWS). An
experience sampling methodology was used to assess sedentary behaviors/screen
time and the social context in which physical activity and sedentary
time/behavior occurred. Physical activity was assessed via accelerometry.
Multilevel models were used to estimate the relationships between predictors
(neighborhood safety and social context) and outcomes (physical activity and
sedentary time/behavior). Frequency of peer/friend interactions moderated the
relationships between neighborhood safety and adolescents' physical activity and
sedentary behavior. Specifically, physical activity was more strongly influenced
by neighborhood safety among adolescents who reported spending less time with
peers and friends than among those who reported frequent peer interactions. Among
youths who perceived that their neighborhoods were safer, spending more time with
friends and peers was related to greater engagement in sedentary activities,
whereas this was not the case among adolescents who perceived that their
neighborhoods were less safe. The peer social context moderates the relationship
between perceived neighborhood safety and adolescents' physical activity and
sedentary behavior. Improving social interactions at the individual level within
neighborhoods may decrease concerns of safety.
PMID- 28491491
TI - Tuberculous pleural effusion occurring concurrently with asbestos-related pleural
disease.
AB - An eighty-four-year-old man presented with progressive exertional dyspnea,
productive cough and weight loss for two months. His physical exam was notable
for diminished breath sounds at the right base, with dullness to percussion.
Chest-x-ray showed moderate right-sided pleural effusion and bilateral calcified
pleural plaques as well as diaphragmatic plaques consistent with asbestos-related
pleural disease (ARPD). Pleural fluid was exudative with predominantly
mononuclear cells, negative acid fast bacilli stain, negative cultures, and
negative cytology for malignant cells. Due to recurrence of the effusion, 4 weeks
after drainage, thoracoscopic pleural biopsy was planned but pleural fluid
cultures came back positive for mycobacteria tuberculosis. Patient was started on
anti-tubercular therapy but treatment had to be stopped due to liver toxicity.
Patient subsequently developed pneumonia and deteriorated despite antibiotic
therapy and expired.
PMID- 28491487
TI - Biomolecular engineering for nanobio/bionanotechnology.
AB - Biomolecular engineering can be used to purposefully manipulate biomolecules,
such as peptides, proteins, nucleic acids and lipids, within the framework of the
relations among their structures, functions and properties, as well as their
applicability to such areas as developing novel biomaterials, biosensing,
bioimaging, and clinical diagnostics and therapeutics. Nanotechnology can also be
used to design and tune the sizes, shapes, properties and functionality of
nanomaterials. As such, there are considerable overlaps between nanotechnology
and biomolecular engineering, in that both are concerned with the structure and
behavior of materials on the nanometer scale or smaller. Therefore, in
combination with nanotechnology, biomolecular engineering is expected to open up
new fields of nanobio/bionanotechnology and to contribute to the development of
novel nanobiomaterials, nanobiodevices and nanobiosystems. This review highlights
recent studies using engineered biological molecules (e.g., oligonucleotides,
peptides, proteins, enzymes, polysaccharides, lipids, biological cofactors and
ligands) combined with functional nanomaterials in nanobio/bionanotechnology
applications, including therapeutics, diagnostics, biosensing, bioanalysis and
biocatalysts. Furthermore, this review focuses on five areas of recent advances
in biomolecular engineering: (a) nucleic acid engineering, (b) gene engineering,
(c) protein engineering, (d) chemical and enzymatic conjugation technologies, and
(e) linker engineering. Precisely engineered nanobiomaterials, nanobiodevices and
nanobiosystems are anticipated to emerge as next-generation platforms for
bioelectronics, biosensors, biocatalysts, molecular imaging modalities,
biological actuators, and biomedical applications.
PMID- 28491492
TI - Associations between hippocampal morphometry and neuropathologic markers of
Alzheimer's disease using 7 T MRI.
AB - Hippocampal atrophy, amyloid plaques, and neurofibrillary tangles are established
pathologic markers of Alzheimer's disease. We analyzed the temporal lobes of 9
Alzheimer's dementia (AD) and 7 cognitively normal (NC) subjects. Brains were
scanned post-mortem at 7 Tesla. We extracted hippocampal volumes and radial
distances using automated segmentation techniques. Hippocampal slices were
stained for amyloid beta (Abeta), tau, and cresyl violet to evaluate neuronal
counts. The hippocampal subfields, CA1, CA2, CA3, CA4, and subiculum were
manually traced so that the neuronal counts, Abeta, and tau burden could be
obtained for each region. We used linear regression to detect associations
between hippocampal atrophy in 3D, clinical diagnosis and total as well as
subfield pathology burden measures. As expected, we found significant
correlations between hippocampal radial distance and mean neuronal count, as well
as diagnosis. There were subfield specific associations between hippocampal
radial distance and tau in CA2, and cresyl violet neuronal counts in CA1 and
subiculum. These results provide further validation for the European Alzheimer's
Disease Consortium Alzheimer's Disease Neuroimaging Initiative Center Harmonized
Hippocampal Segmentation Protocol (HarP).
PMID- 28491493
TI - Brainstem shape is affected by clinical course in the neonatal intensive care
unit.
AB - The brainstem, critical for motor function, autonomic regulation, and many
neurocognitive functions, undergoes rapid development from the third trimester.
Accordingly, we hypothesized it would be vulnerable to insult during this period,
and that a difficult clinical course in the neonatal intensive care unit (NICU)
would affect development, and be reflected through atypical shape. Our study
population consisted of 66 neonates - all inpatients from the NICU at Victoria
Hospital, London Health Sciences Centre, ON, Canada, of which 45 entered the
final analysis. The cohort varied in gestational age (GA) and ranged from
neurologically healthy to severely brain-injured. Structural MRI was used to
quantify brainstem shape at term-equivalent age. From these images, brainstems
were semi-automatically segmented and co-registered across subjects. The anterior
posterior dimensions on a sagittal maximum intensity projection were used as the
basis for shape comparison. Factor analysis was used to summarize variation in
shape and in clinical course to determine three shape factors and three clinical
factors, and their relationship assessed using correlation. A factor driven by
low GA and associated complications correlated with alterations in the posterior
medulla, while a factor driven by complications independent of GA correlated with
alterations in the midbrain. Additionally, single clinical measures most
representative of their respective clinical factor (days in NICU; days on
ventilation) predicted the changes. Thus, different clinical courses in the NICU
may have different effects on the shape of the brainstem, and may mediate some of
the distinct neurodevelopmental profiles observed in premature and brain-injured
neonates.
PMID- 28491494
TI - The relationship between morphological lesion, magnetic source imaging, and
intracranial stereo-electroencephalography in focal cortical dysplasia.
AB - Magnetoencephalography (MEG) is a useful non-invasive technique for presurgical
evaluation of focal cortical dysplasia patients. We aimed at clarifying the
precise spatial relationship between the spiking volume determined with MEG, the
seizure onset zone and the lesional volume in patients with focal cortical
dysplasia. We studied the spatial relationships between the MEG spiking volume
determined with a recent analysis pipeline, the seizure-onset zone location
determined with a quantitative index calculated from intracranial EEG signals
('Epileptogenicity Index') and the lesional volume delineated on brain MRI in 11
patients with Focal Cortical Dysplasia explored with Stereo
electroencephalography (SEEG). A significant correlation between the MEG spiking
activity and the Epileptogenicity Index was found in 8/11 patients. 7/8 patients
were operated upon and had good surgical outcome. For three patients, no
correlation between Epileptogenicity Index and spiking activity was observed;
only one of those three patients had good surgical outcome. The lesion was at
least partially overlapping with the seizure-onset zone in 8/9 patients with a
lesion clearly identifiable by MRI. However, 57% of the SEEG epileptogenic
contacts were located outside of the lesional volume. Lastly 44% of the highly
epileptogenic SEEG contacts were located within the spiking volume and 22% of
them were located exclusively in the spiking volume and not in the lesion. For
7/9 patients with a lesion, < 50% of epileptogenic SEEG contacts were included
within the lesion: for 5/7 patients MEG provided an added value for targeting the
epileptogenic region through intracranial electrodes, while for two of seven
patients MEG detected only a few extralesional epileptogenic contacts. Our study
suggests that modeling of the spiking volume with MEG is a promising tool to
localize non-invasively the seizure-onset zone in patients with focal cortical
dysplasia. Combined with brain MRI, MEG modeling of the spiking volume
contributes to delineate the spatial extent of the seizure-onset zone.
PMID- 28491497
TI - Complete genome sequence of a natural compounds producer, Streptomyces violaceus
S21.
AB - The complete genome sequence of Streptomyces violaceus strain S21, a valuable
natural compounds producer isolated from the forest soil, is firstly presented
here. The genome comprised 7.91M bp, with a G + C content of 72.65%. A range of
genes involved in pathways of secondary product biosynthesis were predicted. The
genome sequence is available at DDBJ/EMBL/Genbank under the accession number
CP020570. This genome is annotated with 6856 predicted genes identifying the
natural product biosynthetic gene clusters in S. violaceus.
PMID- 28491498
TI - Two mechanisms of termination of idiopathic reentrant ventricular tachycardia
originating from the left coronary cusp/right coronary cusp commissure with
nonglobal capture.
PMID- 28491495
TI - Dorsolateral prefrontal cortex contributes to the impaired behavioral adaptation
in alcohol dependence.
AB - Substance-dependent individuals often lack the ability to adjust decisions
flexibly in response to the changes in reward contingencies. Prediction errors
(PEs) are thought to mediate flexible decision-making by updating the reward
values associated with available actions. In this study, we explored whether the
neurobiological correlates of PEs are altered in alcohol dependence. Behavioral,
and functional magnetic resonance imaging (fMRI) data were simultaneously
acquired from 34 abstinent alcohol-dependent patients (ADP) and 26 healthy
controls (HC) during a probabilistic reward-guided decision-making task with
dynamically changing reinforcement contingencies. A hierarchical Bayesian
inference method was used to fit and compare learning models with different
assumptions about the amount of task-related information subjects may have
inferred during the experiment. Here, we observed that the best-fitting model was
a modified Rescorla-Wagner type model, the "double-update" model, which assumes
that subjects infer the knowledge that reward contingencies are anti-correlated,
and integrate both actual and hypothetical outcomes into their decisions.
Moreover, comparison of the best-fitting model's parameters showed that ADP were
less sensitive to punishments compared to HC. Hence, decisions of ADP after
punishments were loosely coupled with the expected reward values assigned to
them. A correlation analysis between the model-generated PEs and the fMRI data
revealed a reduced association between these PEs and the BOLD activity in the
dorsolateral prefrontal cortex (DLPFC) of ADP. A hemispheric asymmetry was
observed in the DLPFC when positive and negative PE signals were analyzed
separately. The right DLPFC activity in ADP showed a reduced correlation with
positive PEs. On the other hand, ADP, particularly the patients with high
dependence severity, recruited the left DLPFC to a lesser extent than HC for
processing negative PE signals. These results suggest that the DLPFC, which has
been linked to adaptive control of action selection, may play an important role
in cognitive inflexibility observed in alcohol dependence when reinforcement
contingencies change. Particularly, the left DLPFC may contribute to this
impaired behavioral adaptation, possibly by impeding the extinction of the
actions that no longer lead to a reward.
PMID- 28491496
TI - Towards in vivo focal cortical dysplasia phenotyping using quantitative MRI.
AB - Focal cortical dysplasias (FCDs) are a range of malformations of cortical
development each with specific histopathological features. Conventional
radiological assessment of standard structural MRI is useful for the localization
of lesions but is unable to accurately predict the histopathological features.
Quantitative MRI offers the possibility to probe tissue biophysical properties in
vivo and may bridge the gap between radiological assessment and ex-vivo
histology. This review will cover histological, genetic and radiological features
of FCD following the ILAE classification and will explain how quantitative voxel-
and surface-based techniques can characterise these features. We will provide an
overview of the quantitative MRI measures available, their link with biophysical
properties and finally the potential application of quantitative MRI to the
problem of FCD subtyping. Future research linking quantitative MRI to FCD
histological properties should improve clinical protocols, allow better
characterisation of lesions in vivo and tailored surgical planning to the
individual.
PMID- 28491499
TI - Sinus bradycardia and chronotropic incompetence associated with single-agent
itraconazole antifungal therapy: A case report.
PMID- 28491500
TI - First direct human evidence of a probable implantable cardioverter-defibrillator
lead-related scar serving as a substrate for ventricular tachycardia.
PMID- 28491501
TI - Right coronary artery ostial stenosis associated with idiopathic ventricular
tachycardia ablation.
PMID- 28491502
TI - Focal atrial fibrillation presenting in the origin of atrial tachycardia.
PMID- 28491503
TI - Progressive modification of rotors in persistent atrial fibrillation by stepwise
linear ablation.
PMID- 28491504
TI - Successful detection of a high-energy electrical short circuit and a "rescue"
shock using a novel automatic shocking-vector adjustment algorithm.
PMID- 28491505
TI - Fracture and retrieval of an Achieve circular mapping catheter in and from a
pulmonary vein during cryoballoon ablation for atrial fibrillation.
PMID- 28491506
TI - An unusual approach to intractable AVNRT in a pediatric patient.
PMID- 28491507
TI - Thrombotic cardiac tamponade after transseptal puncture.
PMID- 28491508
TI - Perimitral atrial flutter associated with a protected coronary sinus after a Maze
IV procedure and concomitant mitral annulus repair.
PMID- 28491509
TI - Shock-induced right ventricular pacing failure caused by a short circuit:
Uncommon but life-threatening complication of the Riata lead.
PMID- 28491510
TI - Abrupt increase in impedance measurements as detected via remote monitoring: What
is the cause?
PMID- 28491511
TI - Pseudo typical atrial flutter occurring after cavotricuspid isthmus ablation in a
patient with a prior history of Senning operation.
PMID- 28491512
TI - Functional permanent 2:1 atrioventricular block treated with cardioneuroablation:
Case report.
PMID- 28491513
TI - Erroneous shock by an AED: Importance of obtaining AED tracing to prevent
inappropriate ICD implantation.
PMID- 28491514
TI - Ablation of parahisian ventricular focus.
PMID- 28491515
TI - Arrhythmogenic triggers associated with an autonomic response from a
posteroseptal region after extensive ablation in a patient with long-standing
atrial fibrillation.
PMID- 28491516
TI - Preferential properties with decremental conduction of the Marshall vein between
the coronary sinus and left superior pulmonary vein.
PMID- 28491517
TI - First case of epicardial ablation to coexistent J waves in the inferior leads in
a patient with clinical diagnosis of Brugada syndrome.
PMID- 28491518
TI - Simultaneous isolation of the four pulmonary veins by single-sided antral
ablation.
PMID- 28491519
TI - A rare variant of pulmonary vein drainage.
PMID- 28491520
TI - A case of incessant VT from an intramural septal focus: Ethanol or bipolar
ablation?
PMID- 28491521
TI - Transjugular lead fragment extraction to improve tricuspid regurgitation.
PMID- 28491522
TI - Accelerated idioventricular rhythm after left atrial tachycardia ablation as a
marker of acute coronary ischemia.
PMID- 28491523
TI - Left anterior descending artery spasm after radiofrequency catheter ablation for
ventricular premature contractions originating from the left ventricular outflow
tract.
PMID- 28491524
TI - Successful catheter ablation of idiopathic ventricular tachycardia originating
from the top of the left ventricular posterior papillary muscle near the chordae
tendineae: Usefulness of intracardiac three-dimensional echocardiography.
PMID- 28491525
TI - Multiple monomorphic ventricular tachycardias in a structurally normal heart: A
case report.
PMID- 28491526
TI - Social anxiety provoked by speech-induced atrial tachycardia.
PMID- 28491527
TI - Laser-assisted extraction of a pacing lead with a supraclavicular course.
PMID- 28491528
TI - Usefulness of a 2-F catheter electrode in a case with successful electrical
isolation of remarkably hypoplastic right inferior pulmonary vein.
PMID- 28491529
TI - Ventricular tachycardia secondary to abandoned epicardial pacemaker lead.
PMID- 28491530
TI - Overcoming an impossible anatomy with a novel left ventricular active fixation
lead in the coronary sinus: A case report.
PMID- 28491531
TI - A case of successful termination of an atrial tachycardia ablated from the
pulmonary artery during rapid ventricular pacing.
PMID- 28491533
TI - Exome sequencing identifies a novel mutation in the MYH6 gene in a family with
early-onset sinus node dysfunction, ventricular arrhythmias, and cardiac arrest.
PMID- 28491532
TI - Successful treatment of flecainide overdose with sustained mechanical circulatory
support.
PMID- 28491534
TI - Role of the His bundle in verapamil-sensitive idiopathic left ventricular
tachycardia.
PMID- 28491535
TI - Parasternal intercostal approach as an alternative to subxiphoid approach for
epicardial catheter ablation: A case report.
PMID- 28491536
TI - Air entrapment causing early inappropriate shocks in a patient with a
subcutaneous cardioverter-defibrillator.
PMID- 28491537
TI - Serious case of the hiccups.
PMID- 28491538
TI - Options for ventricular tachycardia ablation after double valve replacement.
PMID- 28491539
TI - Breast tissue expanders and implantable cardioverter-defibrillator: An unusual
interaction.
PMID- 28491540
TI - Rhabdomyolysis complicating percutaneous radiofrequency ablation of persistent
atrial fibrillation.
PMID- 28491541
TI - Commotio cordis due to high-velocity projectile ejected from an industrial
lawnmower.
PMID- 28491542
TI - Implantation of the subcutaneous implantable cardioverter-defibrillator with
retroperitoneal generator placement in a child with hypoplastic left heart
syndrome.
PMID- 28491543
TI - A true case of wandering pacemaker.
PMID- 28491544
TI - Isolated right ventricular failure and abnormal hemodynamics caused by right
ventricular pacing are reversed with cardiac resynchronization therapy.
PMID- 28491545
TI - Right-sided subcutaneous implantable cardioverter-defibrillator placement in a
patient with dextrocardia, tetralogy of Fallot, and conduction disease.
PMID- 28491546
TI - Persistent sinus node suppression caused by thrombotic occlusion of an
arteriovenous fistula: A report of two cases.
PMID- 28491547
TI - Short QT and atrial fibrillation: A KCNQ1 mutation-specific disease. Late follow
up in three unrelated children.
PMID- 28491548
TI - Pacemaker-induced tachycardia in a DDI-programmed ICD: What is the mechanism?
PMID- 28491549
TI - Extensive atrial fibrosis in a patient with systemic lupus erythematosus and
atrial fibrillation.
PMID- 28491550
TI - Successful catheter ablation of hemodynamically significant ventricular
tachycardia in a patient with biventricular assist device support.
PMID- 28491551
TI - Early repolarization syndrome: A case report focusing on dynamic
electrocardiographic changes before ventricular arrhythmias and genetic analysis.
PMID- 28491552
TI - Radiofrequency ablation-assisted extraction of a pacing lead fragment.
PMID- 28491553
TI - Absence of a resetting phenomenon suggests that a sling works as a part of the
supraventricular tachycardia circuit involving twin atrioventricular nodes: A
case of corrected transposition of the great arteries.
PMID- 28491554
TI - Induction of tachycardia confined within a pulmonary vein by electrical
cardioversion of atrial fibrillation: Is it proof of reentry?
PMID- 28491555
TI - Duelling pacemakers: Unexpected pacemaker interaction resulting from a
proprietary rate smoothing algorithm.
PMID- 28491556
TI - Pseudo-conduction block at the mitral isthmus in a patient with epicardial
impulse propagation through the vein of Marshall.
PMID- 28491558
TI - Successful implantation of a subcutaneous cardiac defibrillator in a patient with
a preexisting deep brain stimulator.
PMID- 28491557
TI - Robot-assisted delayed extraction of retained Lasso catheter combined with mitral
valve repair and arrhythmia ablation.
PMID- 28491559
TI - Successful ablation of refractory neonatal atrial flutter.
PMID- 28491560
TI - Recurrent commotio cordis: Deja vu.
PMID- 28491561
TI - Periesophageal vagal nerve injury following catheter ablation of atrial
fibrillation: A case report and review of the literature.
PMID- 28491562
TI - Inappropriate shocks by subcutaneous implantable cardioverter-defibrillator due
to T-wave oversensing in hyperkalemia leading to ventricular fibrillation.
PMID- 28491563
TI - The use of noninvasive ECG imaging for examination of a patient with Brugada
syndrome.
PMID- 28491564
TI - Direct visualization of induced steam pops during radiofrequency ablation.
PMID- 28491565
TI - Mahaim-type accessory pathway and right bundle branch electroanatomic
delineation.
PMID- 28491566
TI - Challenges in the diagnosis and management of idiopathic ventricular
fibrillation.
PMID- 28491567
TI - Adjusting voltage criteria can unmask conducting channels in a patient with
arrhythmogenic right ventricular cardiomyopathy and ventricular tachycardia.
PMID- 28491568
TI - First-in-human case of repeat pulmonary vein isolation by targeting visual
interlesion gaps using the direct endoscopic ablation catheter after single ring
pulmonary vein isolation.
PMID- 28491570
TI - MediGuide-assisted atrial flutter ablation in a patient with a HeartMate II left
ventricular assist device.
PMID- 28491569
TI - Ventricular fibrillation in lone atrial fibrillation as clinical manifestation of
latent Brugada syndrome: Usefulness of flecainide testing.
PMID- 28491572
TI - Nonobstructive septal hypertrophy in a young adult provoking recurrent
polymorphic ventricular tachycardia successfully treated with transaortic and
transventricular septal myectomy: A case report.
PMID- 28491571
TI - Isolated atrioventricular block of unknown origin in the adult and autoimmunity:
diagnostic and therapeutic considerations exemplified by 3 anti-Ro/SSA-associated
cases.
PMID- 28491573
TI - Recurrent suspected myocarditis combined with infrahisian conduction disturbances
revealing a desminopathy.
PMID- 28491574
TI - Pathology after combined epicardial and endocardial ablation for ventricular
tachycardia in a postmortem heart with hypertrophic cardiomyopathy.
PMID- 28491575
TI - A case series and review of the literature regarding coronary artery
complications associated with coronary sinus catheter ablation.
PMID- 28491576
TI - QRS normalization during atrial pacing in a patient with complete left bundle
branch block: What is your diagnosis?
PMID- 28491577
TI - CT-fusion-guided transseptal puncture in a patient with atrial fibrillation and
absent right superior vena cava.
PMID- 28491578
TI - Fasciculoventricular accessory pathways following repair of ventricular septal
defects.
PMID- 28491579
TI - Ankyrin-2 variants associated with idiopathic ventricular fibrillation storm in
patients with intermittent early repolarization pattern.
PMID- 28491580
TI - Relation of overweight and symptomatic atrial fibrillation: A case report.
PMID- 28491581
TI - Discrete prepotentials with an isoelectric segment at the successful ablation
site in the right ventricular outflow tract and pulmonary artery junction in a
case with a ventricular arrhythmia.
PMID- 28491582
TI - Atrial pacing for the management of ventricular arrhythmias in Andersen-Tawil
syndrome.
PMID- 28491583
TI - Implantation of a cardiac resynchronization therapy and defibrillation system
using a robotic approach.
PMID- 28491584
TI - Atrial fibrillation ablation performed in the developing world: A description of
the first atrial fibrillation ablation performed in Cambodia.
PMID- 28491585
TI - Ventricular fibrillation a rare complication during head-up tilt test.
PMID- 28491586
TI - A very rare abnormal course of the thoracic venous system: Long journey to the
right ventricle.
PMID- 28491587
TI - Unusual mechanism of complete atrioventricular block following atrial flutter
ablation.
PMID- 28491588
TI - The lack of effect of sotalol in short QT syndrome patients carrying the T618I
mutation in the KCNH2 gene.
PMID- 28491589
TI - Circular mapping recordings in a persistent left superior vena cava during atrial
tachycardia: Was isolation achieved?
PMID- 28491590
TI - Left ventricle penetration-A rare complication of transseptal puncture and
catheter ablation for supraventricular tachycardia.
PMID- 28491591
TI - Rapidly formed right ventricular thrombus detected by intracardiac
echocardiography before catheter ablation in a case of arrhythmogenic right
ventricular cardiomyopathy.
PMID- 28491592
TI - Intentional anodal capture of a left ventricular quadripolar lead enhances
resynchronization equally with multipoint pacing.
PMID- 28491593
TI - Congenital long QT syndrome: A difficult journey for one young survivor.
PMID- 28491594
TI - Successful stent implantation for superior vena cava injury during transvenous
lead extraction.
PMID- 28491596
TI - An unusual atrioventricular accessory pathway with an oblique course.
PMID- 28491595
TI - High-power bipolar ablation for incessant ventricular tachycardia utilizing a
deep midmyocardial septal circuit.
PMID- 28491597
TI - The presence of left atrial posterior wall fibrillation despite restoration of
sinus rhythm after posterior box ablation.
PMID- 28491598
TI - Nothing inside the heart - Combining epicardial pacing with the S-ICD.
PMID- 28491599
TI - Visualization of pulmonary vein-left atrium lesions using delayed-enhancement
magnetic resonance imaging after cryothermal balloon catheter ablation: A case
report.
PMID- 28491600
TI - Incessant bundle branch reentrant ventricular tachycardia in a patient with
corrected transposition of the great arteries.
PMID- 28491601
TI - A case of ventricular fibrillation triggered by ventricular premature
depolarizations exiting from different sites of the Purkinje network.
PMID- 28491602
TI - A balloon occlusion technique to overcome the convective warming effect of
coronary sinus blood flow on cryoablation.
PMID- 28491603
TI - Patients with hemophilia: Unique challenges for atrial fibrillation management.
PMID- 28491604
TI - A case series of anomalous high pacing lead impedances in normally functioning
leads.
PMID- 28491605
TI - Parsing a perplexing paroxysmal pathway.
PMID- 28491606
TI - Left atrial access via an unroofed coronary sinus to eliminate fast/slow atypical
AVNRT: A case report.
PMID- 28491607
TI - Reuse of a 20-year-old lead: An abandoned lead reactivated.
PMID- 28491608
TI - Prolonged high-power endocardial ablation of epicardial microreentrant VT from
the LV summit in a patient with nonischemic cardiomyopathy.
PMID- 28491609
TI - Combination of a leadless pacemaker and subcutaneous defibrillator: First in
human report.
PMID- 28491610
TI - Long-term follow-up of minimally invasive video-assisted thoracoscopic surgery
with epicardial radiofrequency ablation for complex cases of inappropriate sinus
tachycardia.
PMID- 28491611
TI - Acquired right atrial appendage to right ventricle accessory pathway in a lateral
tunnel Fontan patient: Successful ablation via transconduit approach.
PMID- 28491612
TI - Radiofrequency ablation of common atrial flutter via right subclavian/jugular
vein access in a patient with bilateral lower limb venous obstruction: Importance
of contact force monitoring during mapping and ablation.
PMID- 28491613
TI - Late atrial tachycardia originating from donor pulmonary vein in a double lung
transplant recipient.
PMID- 28491614
TI - Choking-induced cardiac arrest unmasks a diagnosis of catecholaminergic
polymorphic ventricular tachycardia.
PMID- 28491615
TI - To eat, or not to eat...?: A live video case of swallowing-induced atrial
tachycardia.
PMID- 28491616
TI - Partial extravenous course of cardiac pacemaker leads. A major risk during device
assisted extraction.
PMID- 28491617
TI - Direct visualization of an iatrogenic septal defect in a reanimated human heart.
PMID- 28491618
TI - State of the journal 2016: HeartRhythm Case Reports.
PMID- 28491619
TI - Feasibility of tricuspid valve-in-valve replacement in a patient with
transvalvular pacemaker.
PMID- 28491621
TI - Central venous catheter fracture during pacemaker lead extraction.
PMID- 28491620
TI - Turning a blind eye to the far field: Are we burying the evidence? A case of
abrupt catastrophic implantable cardioverter defibrillator lead failure causing
sudden death.
PMID- 28491622
TI - Combined use of TandemHeart percutaneous ventricular assist device and
Stereotaxis magnetic navigation during cardiac ablation procedure.
PMID- 28491623
TI - Simultaneous lead extraction and vacuum-assisted vegetation removal.
PMID- 28491624
TI - Salvage of diagnostic quality of image acquired by low-radiation-dose
prospectively ECG-triggered coronary CTA during ventricular trigeminy: A case
report of a novel image processing method.
PMID- 28491625
TI - Premature extrastimulus pace-mapping to identify the origin of ventricular
premature depolarizations.
PMID- 28491626
TI - Bradycardia-dependent rise in the atrial capture threshold early after cardiac
pacemaker implantation in patients with sick sinus syndrome.
PMID- 28491627
TI - A novel GJA1 mutation causing familial oculodentodigital dysplasia with dilated
cardiomyopathy and arrhythmia.
PMID- 28491628
TI - Physiological rate adaptation in a child with chronotropic incompetence through
closed-loop stimulation using epicardial leads.
PMID- 28491629
TI - The runaway defibrillator...A case of an implantable cardioverter-defibrillator
that failed communication and deactivation with a magnet.
PMID- 28491630
TI - Retrieval of a transcatheter pacemaker in sheep after a mid-term implantation
time.
PMID- 28491631
TI - Epicardial mapping and ablation of the right ventricle substrate during
flecainide testing in Brugada syndrome.
PMID- 28491632
TI - Rapidly progressive cardiac sarcoidosis: Initial presentation with sinus node
dysfunction and right bundle branch block.
PMID- 28491633
TI - Extraction of a Micra Transcatheter Pacing System: First-in-human experience.
PMID- 28491634
TI - Irregular wide QRS complex tachycardia in a patient with pulmonary hypertension:
What is the mechanism?
PMID- 28491635
TI - Single-catheter validation of bidirectional block during atrial flutter ablation.
PMID- 28491636
TI - Multiple atrial thrombi in a neonate presenting with supraventricular
tachycardia.
PMID- 28491637
TI - Dobutamine-induced midcavitary gradients do not cause dyspnea.
PMID- 28491638
TI - Standard cardiac resynchronization therapy with a second right ventricular lead
for severe right ventricular heart failure in 2 patients with repaired tetralogy
of Fallot.
PMID- 28491639
TI - Fibrin glue patch for pacemaker lead perforation of the right ventricular free
wall: A case report.
PMID- 28491640
TI - Swallow-induced syncope: A case report of atrial tachycardia originating from the
SVC.
PMID- 28491641
TI - Benefit of magnetic resonance-conditional cardiac resynchronization therapy
defibrillator: A case of cardiac sarcoidosis-involved cervical extradural lesion.
PMID- 28491642
TI - A novel ACTC1 mutation in a young boy with left ventricular noncompaction and
arrhythmias.
PMID- 28491643
TI - Ventricular tachycardia in iron man.
PMID- 28491644
TI - Upper septal transformation of verapamil-sensitive idiopathic left ventricular
tachycardia during catheter ablation: Wolf in sheep's clothing?
PMID- 28491645
TI - Tachycardia-induced cardiomyopathy long after a pacemaker implantation for the
treatment of unusual 2:1 atrioventricular block: What is the mechanism?
PMID- 28491646
TI - Pericardial adhesions as a consequence of cryoballoon ablation detected during
the hybrid AF ablation procedure.
PMID- 28491647
TI - Catheter ablation for the treatment of persistent atrial fibrillation:
Maintenance of sinus rhythm with left atrial appendage and coronary sinus
isolation after multiple ablation procedures.
PMID- 28491648
TI - Successful atrioventricular junction ablation in a patient with situs inversus
with dextrocardia and complex venous anatomy.
PMID- 28491649
TI - Atrial Tachycardia in a Patient With Fabry's Disease.
PMID- 28491650
TI - Familial long QT syndrome and late development of dilated cardiomyopathy in a
child with a KCNQ1 mutation: A case report.
PMID- 28491651
TI - Left ventricular tachycardia ablation in a toddler via a transapical approach: A
new tool for the armamentarium.
PMID- 28491652
TI - Implantation of ileofemoral stents: A novel approach for bilateral occlusions of
the iliofemoral vein in a patient with a Glenn operation.
PMID- 28491653
TI - Incessant atrioventricular nodal reentrant tachycardia with tachycardia-induced
cardiomyopathy, biventricular thrombosis, and pulmonary emboli.
PMID- 28491654
TI - Phrenic nerve pacing in a patient with congenital atresia of the right superior
vena cava and persistent left superior vena cava: An alternative approach when
utilizing cryoballoon ablation.
PMID- 28491655
TI - Paradoxical preexcitation following successful ablation of a concealed accessory
pathway.
PMID- 28491656
TI - Successful interventional management of catastrophic coronary arterial air
embolism during atrial fibrillation ablation.
PMID- 28491657
TI - ICD lead abandonment is without risk? A case of "lead on lead crime".
PMID- 28491658
TI - An atrial flutter in a 40-year-old woman with situs inversus, transposition of
the great arteries, atrial switch, and interruption of the inferior vena cava.
PMID- 28491659
TI - Reduced combined ventricular output and increased oxygen extraction fraction in a
fetus with complete heart block demonstrated by MRI.
PMID- 28491660
TI - Occlusion of a congenital right coronary-to-vena cava superior fistula induces
temporary junctional bradycardia and atrial fibrillation.
PMID- 28491661
TI - Diagnosis of lead-induced tricuspid regurgitation.
PMID- 28491662
TI - Intermittent failure to capture: What is the mechanism?
PMID- 28491663
TI - Epicardial ablation of ventricular tachycardia in a patient with Becker muscular
dystrophy.
PMID- 28491664
TI - Successful retrieval of a broken circular mapping catheter after entrapment in
the tricuspid valve apparatus.
PMID- 28491665
TI - Mechanical esophageal deviation: an approach for pulmonary vein reconnection
attributed to esophageal heating.
PMID- 28491666
TI - An atypical journey during a "typical" EP case.
PMID- 28491667
TI - Supraspinatus pocket: An alternative pacemaker location for patients with no
prepectoral access.
PMID- 28491668
TI - PentaRay entrapment in a mechanical mitral valve during catheter ablation of
atrial fibrillation.
PMID- 28491669
TI - Isolation of an arrhythmogenic roof vein with the guide of a circular mapping
catheter in a case with paroxysmal atrial fibrillation.
PMID- 28491670
TI - Premature ventricular contractions with two QRS morphologies originate from one
focus in great cardiac vein.
PMID- 28491671
TI - Extraction of a CardioFix neurostimulator with concomitant laser-assisted lead
and intracardiac cardiac defibrillator extraction due to Staphylococcus aureus
pocket infection.
PMID- 28491672
TI - Correlation between functional and ultrastructural substrate in Brugada syndrome.
PMID- 28491673
TI - Failure of ICD therapy in lethal arrhythmogenic right ventricular cardiomyopathy
type 5 caused by the TMEM43 p.Ser358Leu mutation.
PMID- 28491674
TI - Normalization of QT interval duration in a long QT syndrome patient during
pregnancy and the postpartum period due to sex hormone effects on cardiac
repolarization.
PMID- 28491675
TI - Management of life-threatening flecainide overdose: A case report and review of
the literature.
PMID- 28491676
TI - High-dose loperamide abuse-associated ventricular arrhythmias.
PMID- 28491677
TI - Flecainide and elevated liver enzymes in alpha1-antitrypsin deficiency.
PMID- 28491678
TI - Transhepatic radiofrequency ablation of a cavotricuspid isthmus-dependent atrial
flutter.
PMID- 28491679
TI - Cardiac resynchronization therapy device implantation guided by electroanatomic
mapping system when contrast medium infusion is contraindicated.
PMID- 28491680
TI - A Medwatch review of reported events in patients who discontinued rivaroxaban
(XARELTO) therapy in response to legal advertising.
PMID- 28491681
TI - Novel CALM3 mutations in pediatric long QT syndrome patients support a CALM3
specific calmodulinopathy.
PMID- 28491682
TI - Radiofrequency ablation of premature ventricular contractions originating from
the aortomitral continuity localized by use of a novel noninvasive epicardial and
endocardial electrophysiology system.
PMID- 28491683
TI - Cryoablation of an atrioventricular nodal reentrant tachycardia in a patient with
an implanted deep brain stimulator.
PMID- 28491684
TI - Repeated molecular genetic analysis in Brugada syndrome revealed a novel disease
associated large deletion in the SCN5A gene.
PMID- 28491686
TI - Absence of exit block due to direct capture of the left atrial appendage: A
visual confirmation.
PMID- 28491685
TI - Radiofrequency wire-facilitated transseptal access using a superior approach for
atrial fibrillation ablation in a patient with inferior vena cava obstruction.
PMID- 28491687
TI - Subcutaneous ICD implant complicated by an intraperitoneal lead course and device
infection.
PMID- 28491688
TI - Pacemaker-induced takotsubo cardiomyopathy.
PMID- 28491689
TI - Concomitant pulsus and pseudoelectrical alternans in severe systolic dysfunction.
PMID- 28491690
TI - Dexamethasone suppresses long QT phenotype in patient with acute promyelocytic
leukemia treated with arsenic.
PMID- 28491691
TI - A case of Durata ICD lead coil externalization: Inside-out lead abrasion?
PMID- 28491692
TI - Intermittent failure of pacing output caused by algorithm to prevent T-wave
oversensing.
PMID- 28491693
TI - Congenital heart disease confounding the diagnosis of arrhythmogenic right
ventricular cardiomyopathy.
PMID- 28491694
TI - Emergent use of an MRI-conditional external pacemaker in a patient with sinus
arrest facilitating diagnosis of a temporal lobe neoplasm.
PMID- 28491695
TI - Successful totally thoracoscopic management of a superior vena cava perforation
with a pacemaker lead.
PMID- 28491696
TI - A rare case of epicardial left ventricular sutureless screw-in lead placement
causing left anterior descending artery stenosis.
PMID- 28491697
TI - Swallowing-induced atrial tachycardia arising from superior vena cava:
Significant involvement of parasympathetic nerve activity.
PMID- 28491698
TI - Idiopathic left innominate vein stenosis during pacemaker implantation with
venoplasty in a retrograde approach.
PMID- 28491699
TI - Orthostatic increase in defibrillation threshold leading to defibrillation
failure and prolonged cardiac arrest in a sitting position: Lessons from a
patient's near-fatal experience.
PMID- 28491700
TI - Percutaneous extraction of a 20-year-old Accufix pacemaker lead complicated by
intraoperative protrusion of its J retention wire.
PMID- 28491701
TI - Undetected ventricular fibrillation in a single-chamber implantable cardioverter
defibrillator: When the far-field channel sees more than the intraventricular
channel.
PMID- 28491702
TI - Late resolution of pacemaker lead-related severe tricuspid regurgitation and
right ventricular dysfunction after percutaneous lead extraction: A case report
and review of the literature.
PMID- 28491704
TI - Pre-excited tachycardia: Atrial tachycardia with a bystander left lateral
accessory pathway.
PMID- 28491703
TI - Cardiac arrest in an adolescent with Uhl's anomaly: Two unusual cardiac
arrhythmia mechanisms.
PMID- 28491705
TI - Implantation of a leadless cardiac pacemaker for recurrent pocket infections.
PMID- 28491706
TI - Radiofrequency catheter ablation for treatment of premature ventricular
contractions triggering ventricular fibrillation from the right ventricular
outflow tract in a patient with early repolarization syndrome.
PMID- 28491707
TI - Low room temperature can trigger ventricular fibrillation in J wave syndromes.
PMID- 28491708
TI - Successful catheter ablation using real-time ultrasound-assisted 3-D
electroanatomical mapping system for atrioventricular accessory pathway in a 1
year-old girl with criss-cross heart.
PMID- 28491709
TI - Atrial tachycardia in an electrically dissociated native right atrium after heart
transplantation.
PMID- 28491710
TI - Treating an infected transcatheter pacemaker system via percutaneous extraction.
PMID- 28491711
TI - Preferential conduction during focal atrial tachycardia arising from the
noncoronary cusp.
PMID- 28491712
TI - "Left ventricular" AV nodal reentrant tachycardia: Case report and review of the
literature.
PMID- 28491713
TI - Cavotricuspid isthmus high-density mapping.
PMID- 28491714
TI - Delayed cardiac perforation of the Durata implantable cardioverter-defibrillator
lead more than 1 year after implantation.
PMID- 28491715
TI - Ablation of a symptomatic spontaneous automatic focus arising from an
atriofascicular fiber.
PMID- 28491716
TI - B-cell lymphoma of the pericardium presenting with ventricular tachycardia with a
successful catheter ablation.
PMID- 28491717
TI - 'Runaway' vagal nerve stimulator: a case of cyclic asystole.
PMID- 28491719
TI - Abdominal implantable cardioverter-defibrillator placement in a patient requiring
bilateral chest radiation therapy.
PMID- 28491718
TI - T-wave oversensing during drug challenge test after subcutaneous implantable
cardioverter-defibrillator implantation in a patient with Brugada syndrome.
PMID- 28491720
TI - Wolff-Parkinson-White as a bystander in a patient with aborted sudden cardiac
death.
PMID- 28491721
TI - A unique case of pulmonary embolism presenting as a paroxysmal atrial tachycardia
instigated only by recumbency and stooping.
PMID- 28491722
TI - Appearance of J wave in the inferolateral leads and ventricular fibrillation
provoked by mild hypothermia in a patient with Brugada syndrome.
PMID- 28491723
TI - Substernal implantation of a subcutaneous implantable cardioverter-defibrillator
in a patient with preexisting Hemodialysis Reliable Outflow graft.
PMID- 28491724
TI - Spectrum of cardiac manifestations from aconitine poisoning.
PMID- 28491725
TI - Recurrent and late-onset coronary spasms after cryoballoon ablation procedure in
a patient with atrial fibrillation.
PMID- 28491726
TI - Endocardial-only catheter ablation with substantial improvement in ventricular
fibrillation recurrences in a patient with Brugada syndrome.
PMID- 28491727
TI - Cardiac resynchronization therapy in coronary sinus atresia delivered using
leadless endocardial pacing.
PMID- 28491728
TI - A case of Takotsubo cardiomyopathy showing two modes of initiation for
ventricular fibrillation: Augmented J-wave and torsade de pointes with QT
prolongation.
PMID- 28491729
TI - Late presentation of constrictive pericarditis after limited epicardial ablation
for inappropriate sinus tachycardia.
PMID- 28491730
TI - Graft-versus-host disease: A rare complication of device implantation.
PMID- 28491731
TI - Repeat inappropriate defibrillator discharges following defibrillator
implantation. What is the mechanism and treatment?
PMID- 28491732
TI - High-density mapping of the tachycardia circuit in atrioventricular nodal
reentrant tachycardia.
PMID- 28491733
TI - Reply to the Editor - Regarding swallowing-induced atrial tachycardia arising
from superior vena cava: Significant involvement of parasympathetic nerve
activity.
PMID- 28491734
TI - To the Editor-Swallowing-induced atrial tachycardia arising from superior vena
cava: significant involvement of parasympathetic nerve activity.
PMID- 28491735
TI - Air emboli during the procedure of transcatheter left atrial appendage closure.
PMID- 28491736
TI - An unusual cause of HV prolongation.
PMID- 28491737
TI - Catheter ablation of ventricular tachycardia in the setting of electrical storm
after revascularization of a chronic total occlusion of the right coronary
artery: An uncommon presentation of reperfusion arrhythmia.
PMID- 28491738
TI - IRX3 variant as a modifier of Brugada syndrome with frequent ventricular
fibrillation.
PMID- 28491739
TI - Incremental value of electroanatomical mapping for the diagnosis of
arrhythmogenic right ventricular cardiomyopathy in a patient with sustained
ventricular tachycardia.
PMID- 28491740
TI - Inhibition of pacing in a dependent patient with an implantable cardioverter
defibrillator and a left ventricular assist device.
PMID- 28491742
TI - A transseptal puncture hazard that was close!
PMID- 28491741
TI - Inappropriate shocks in a patient with a subcutaneous implantable cardioverter
defibrillator.
PMID- 28491743
TI - Quinidine for Brugada syndrome: Panacea or poison?
PMID- 28491744
TI - Coronary artery vasospasm during catheter cryoablation of left ventricular summit
nonsustained ventricular tachycardia.
PMID- 28491745
TI - Transvenous approach to pacemaker lead implantation for sinus node dysfunction
after extracardiac lateral tunnel Fontan conduit placement.
PMID- 28491746
TI - Getting to the right left atrium: Catheter ablation of atrial fibrillation and
mitral annular flutter in cor triatriatum.
PMID- 28491747
TI - Flecainide-induced incessant orthodromic atrioventricular reentrant tachycardia
in Wolff-Parkinson-White syndrome: Uneven depression of accessory pathway
conduction.
PMID- 28491748
TI - Percutaneous extraction of a pulmonary artery catheter inadvertently sewn to the
right atrial wall.
PMID- 28491749
TI - Recurrent flash pulmonary edema due to rate-dependent left bundle branch block.
PMID- 28491750
TI - Electroanatomical high-density mapping of different tachycardias in the right
atrium after heart transplantation.
PMID- 28491752
TI - Vagally mediated ventricular arrhythmia in Brugada syndrome.
PMID- 28491753
TI - Clinical problem solving: Maneuvering around a narrow complex tachycardia in a
patient with Mustard repair for transposition of the great arteries.
PMID- 28491751
TI - Structural interplay of KV7.1 and KCNE1 is essential for normal repolarization
and is compromised in short QT syndrome 2 (KV7.1-A287T).
PMID- 28491754
TI - State of the Journal 2017: HeartRhythm Case Reports.
PMID- 28491755
TI - Pericardial-esophageal fistula complicating cryoballoon ablation for refractory
atrial fibrillation.
PMID- 28491756
TI - Radiation-associated plasmacytoma following catheter ablation for atrial
fibrillation.
PMID- 28491757
TI - Successful use of bivalirudin in place of heparin infusion for pulmonary vein
isolation using a cryoballoon catheter in a patient with heparin allergy.
PMID- 28491758
TI - Atrial fibrillation associated with Wolff-Parkinson-White syndrome in a patient
with concomitant Brugada syndrome.
PMID- 28491759
TI - Termination of anticoagulation therapy at 45 days after concomitant atrial
fibrillation catheter ablation and left atrial appendage occlusion resulting in
device-related thrombosis and stroke.
PMID- 28491760
TI - Hierarchical analysis of electrograms to guide termination of persistent atrial
fibrillation.
PMID- 28491761
TI - Use of Biotronik closed loop pacemaker to treat recurrent syncope in pediatric
patient with dysautonomia.
PMID- 28491762
TI - Cardiac resynchronization therapy in persistent left superior vena cava: Can you
do it two-leads-only?
PMID- 28491764
TI - Pulmonary vein stenosis after second-generation cryoballoon ablation for atrial
fibrillation.
PMID- 28491763
TI - Who is the guilty among these two silent killers?
PMID- 28491765
TI - Systemic infection due to subcutaneous implantable cardioverter-defibrillator
implantation: Importance of early recognition and treatment of device pocket
related complications.
PMID- 28491766
TI - Progressive electrical remodeling in apical hypertrophic cardiomyopathy leading
to implantable cardioverter-defibrillator sensing failure during ventricular
fibrillation.
PMID- 28491767
TI - Interference dissociation in the presence of dual atrioventricular nodal
physiology.
PMID- 28491768
TI - Successful prenatal management of ventricular tachycardia and second-degree
atrioventricular block in fetal long QT syndrome.
PMID- 28491769
TI - Surgical and electrophysiological considerations in the management of a patient
with a subcutaneous implantable cardioverter-defibrillator undergoing coronary
artery bypass surgery.
PMID- 28491770
TI - Successful treatment of tachycardia-induced cardiomyopathy secondary to dual
atrioventricular nodal nonreentrant tachycardia using cryoablation.
PMID- 28491771
TI - A novel de novo calmodulin mutation in a 6-year-old boy who experienced an
aborted cardiac arrest.
PMID- 28491772
TI - Recurrent syncope due to glossopharyngeal neuralgia.
PMID- 28491773
TI - Inappropriate subcutaneous implantable cardioverter-defibrillator therapy due to
R-wave amplitude variation: Another challenge in device management.
PMID- 28491774
TI - Dissociation of right and left AV conduction: What is the mechanism?
PMID- 28491775
TI - A case of an ablation catheter entrapped in the pulmonary vein during atrial
fibrillation ablation requiring open heart surgery for removal.
PMID- 28491776
TI - Early improvement of pacing threshold following primary right coronary
angioplasty.
PMID- 28491777
TI - A simple method to ablate left-sided accessory pathways in a patient with
coronary sinus ostial atresia and persistent left superior vena cava: A case
report.
PMID- 28491778
TI - Substernal ICD lead implantation in a patient not suitable for subcutaneous ICD
implantation without venous access due to superior vena cava syndrome.
PMID- 28491780
TI - Complexity of ranolazine and phenytoin use in an infant with long QT syndrome
type 3.
PMID- 28491779
TI - Missed diagnosis: Dual right ventricular lead perforation resulting in chest
pain.
PMID- 28491781
TI - Radiofrequency catheter ablation for drug-refractory paroxysmal atrial
fibrillation in a patient with Ebstein's anomaly.
PMID- 28491782
TI - Ultrarapid identification of activation channels within the scar using high
density mapping from a basket catheter.
PMID- 28491783
TI - Atrioventricular block and pause-dependent torsade de pointes.
PMID- 28491784
TI - Vein of Marshall partially isolated with radiofrequency ablation from the
endocardium.
PMID- 28491785
TI - Junctional ectopic tachycardia secondary to myocarditis associated with sudden
cardiac arrest.
PMID- 28491786
TI - Trans-Fontan baffle placement of an endocardial systemic ventricular pacing lead.
PMID- 28491787
TI - Ventricular tachycardia slower than the rate cut-off of a subcutaneous cardiac
defibrillator sensed and successfully treated as a result of oversensing.
PMID- 28491788
TI - Unstable accelerated idioventricular rhythm in a neonate with congenital heart
disease.
PMID- 28491789
TI - Resuscitated sudden cardiac death due to diminutive coronary artery syndrome.
PMID- 28491790
TI - Electroanatomic mapping of atrial tachycardia-Manual vs automated annotation.
PMID- 28491791
TI - Malfunction of an MRI-Conditional Pacemaker Following an MRI.
PMID- 28491792
TI - Flecainide treats a novel KCNJ2 mutation associated with Andersen-Tawil syndrome.
PMID- 28491793
TI - Bicuspid aortic valve supporting supravalvular "substrate" for multiple
ventricular tachycardias.
PMID- 28491794
TI - Successful catheter ablation of recipient left ventricular tachycardia 26 years
after heterotopic heart transplantation.
PMID- 28491795
TI - Electrophysiological evidence of localized reentry as a trigger and driver of
atrial fibrillation at the junction of the superior vena cava and right atrium.
PMID- 28491796
TI - LAMP2 shines a light on cardiomyopathy in an athlete.
PMID- 28491798
TI - Simultaneous atrioventricular node ablation and leadless pacemaker implantation.
PMID- 28491799
TI - To the Editor - Cardiac resynchronization therapy in coronary sinus atresia
delivered using leadless endocardial pacing.
PMID- 28491797
TI - Bundle branch reentrant ventricular tachycardia after transcatheter aortic valve
replacement.
PMID- 28491800
TI - Reply to the Editor - Regarding Cardiac Resynchronization Therapy in Coronary
Sinus Atresia Delivered Using Leadless Endocardial Pacing.
PMID- 28491801
TI - Iatrogenic pleuropericardial communication: A rare complication of percutaneous
epicardial mapping.
PMID- 28491802
TI - Protecting the right phrenic nerve during catheter ablation: Techniques and
anatomical considerations.
PMID- 28491803
TI - Near-zero fluoroscopy implantation of dual-chamber pacemaker in pregnancy using
electroanatomic mapping.
PMID- 28491804
TI - A surgeon with symptomatic ventricular tachycardia while operating and
exacerbated by left lateral decubitus position: Too much of a stretch?
PMID- 28491805
TI - Worsening of mitral valve regurgitation after radiofrequency catheter ablation of
ventricular arrhythmia originating from a left ventricular papillary muscle.
PMID- 28491806
TI - Atypical long QT syndrome phenotype in heterozygous/homozygous KCNQ1 Ala590Thr.
PMID- 28491807
TI - Microreentrant left atrial tachycardia circuit mapped with an ultra-high-density
mapping system.
PMID- 28491808
TI - Cardiac contractility modulation therapy: Are there superresponders?
PMID- 28491809
TI - Early-stage left atrial intramural hemorrhage mimicking partial coronary sinus
thrombosis in a patient who received ablation for atrial tachyarrhythmias.
PMID- 28491810
TI - Oversensing of atrial fibrillatory waves in a subcutaneous implantable
cardioverter-defibrillator.
PMID- 28491811
TI - An infected cyst due to a congenital pulmonary airway malformation.
PMID- 28491812
TI - Acremonium pneumonia in an AIDS patient.
AB - Acremonium is a saprophytic fungus mostly causing superficial skin, nail, or
ocular infections after traumatic inoculation. However, it is being recently
recognized as one of the opportunistic infections in immunocompromised patients
including neutropenia, malignancies, chronic granulomatous disease (CGD) and
transplant recipients. To our knowledge there have been no reported cases of
Acremonium infection, related to HIV or AIDS. We present a case of Acremonium
pneumonia in a patient with no past medical history who was found to have AIDS.
PMID- 28491813
TI - Toxic shock syndrome due to community-acquired methicillin-resistant
Staphylococcus aureus infection: Two case reports and a literature review in
Japan.
AB - Community-acquired methicillin-resistant Staphylococcus aureus has been spreading
worldwide, including in Japan. However, few cases of toxic shock syndrome caused
by Community-acquired methicillin-resistant Staphylococcus aureus have been
reported in Japan. We report 2 cases, in middle-aged women, of toxic shock
syndrome due to Community-acquired methicillin-resistant Staphylococcus aureus
via a vaginal portal of entry. The first patient had used a tampon and the second
patient had vaginitis due to a cleft narrowing associated with vulvar lichen
sclerosus. Both patients were admitted to our hospital with septic shock and
severe acute kidney injury and subsequently recovered with appropriate antibiotic
treatment. In our review of the literature, 8 cases of toxic shock syndrome
caused by Community-acquired methicillin-resistant Staphylococcus aureus were
reported in Japan. In these 8 cases, the main portals of entry were the skin and
respiratory tract; however, the portal of entry of Community-acquired methicillin
resistant Staphylococcus aureus from a vaginal lesion has not been reported in
Japan previously.
PMID- 28491814
TI - Varicella-zoster virus (VZV) multifocal vasculopathy in a patient with systemic
lupus erythematosus - a diagnostic and treatment dilemma.
AB - Cerebral vasculopathy due to varicella-zoster virus (VZV) infection is well
documented. We report a fatal case of VZV multifocal vasculopathy in a patient
with systemic lupus erythematosus (SLE) who presented with subacute changes in
mental status and had multiple areas of hemorrhagic infarcts on brain imaging.
However, the correct diagnosis was delayed by several confounding factors
including the absence of zoster rash, normal cerebral angiography, persistently
low cerebrospinal fluid (CSF) glucose and negative initial polymerase chain
reaction (PCR) for VZV DNA in the CSF. Our case and literature review suggests
that the sensitivity of PCR for VZV DNA in the CSF is low in VZV vasculopathy and
clinical suspicion of this disease in the setting of characteristic imaging
findings could be crucial to timely diagnosis.
PMID- 28491815
TI - Lethal pulmonary hemorrhage syndrome due to Leptospira infection transmitted by
pet rat.
AB - Human infection with Leptospira interrogans can be life-threatening. Multiple
organ involvement frequently presents with liver and kidney failure, less
commonly including severe hemolysis and pulmonary hemorrhage syndrome. Here, we
present a fulminant case of leptospirosis presenting with hemolysis and pulmonary
hemorrhage. A formerly healthy 34 year old patient presented to a rural hospital
with dyspnea and hemoptysis after a week of influenza-like symptoms. Initial
assessment revealed severe sepsis, acute kidney failure and severe hemolysis.
Within the next 29 h, a multi-organ failure developed, which could eventually not
be reversed despite mechanical ventilation, venovenous extracorporeal membrane
oxygenation, continuous renal replacement therapy, plasmapheresis and
extracorporeal cytokine absorbent therapy. The diagnosis of leptospirosis was
made after the patient died. The transmitting animal was a pet rat. Leptospirosis
has to be considered in case of rapid multi-organ failure presenting with
pulmonary hemorrhage.
PMID- 28491816
TI - Treatment adherence during childhood in individuals with phenylketonuria: Early
signs of treatment discontinuation.
AB - INTRODUCTION: Phenylketonuria (PKU) is an autosomal recessive disorder
characterized by a deficiency in phenylalanine (Phe) hydroxylase activity. Early
diagnosis and continuous treatment with a low Phe diet prevents severe
neurological and cognitive impairment. AIMS: 1. Analyze how treatment adherence
evolves through infancy, childhood, and early adolescence in individuals with
PKU. 2. Identify early signs of treatment discontinuation. METHODOLOGY: This
longitudinal, retrospective study included 75 children diagnosed through newborn
screening, ages 7 to 13 years. Data on blood Phe concentration, number of blood
samples sent, proportion of samples with Phe concentrations over the recommended
range, and number of visits to the metabolism clinic were recorded. Logistic
regression analysis was used to identify the variables that predict treatment
discontinuation before 13 years of age. RESULTS: A progressive increase in mean
blood Phe concentrations with age was identified. The greatest increase occurred
between the first and second years of life. By age ten, mean Phe blood
concentration of the group was above the recommended range. The proportion of
samples with Phe concentrations over the recommended range also increased with
age, from an average of 13% during the first year of life to 67% in early
adolescence. Sixty-eight percent of the children attended the outpatient clinic
and sent samples from birth to the time of the study. Individuals who
discontinued follow-up showed significantly higher mean blood Phe concentrations
(360 vs. 220.9 MUmol/L; p = 0.004) and the proportion of samples over the
recommended range (37% vs. 12% p = 0.002) was significantly higher during the
second year of life. Mean age for children who discontinued treatment was 5.5
years of age. Blood Phe concentration values at 12 to 23 months of age and at 6
to 8 years of age significantly predicted treatment discontinuation before 13
years of age. CONCLUSION: Treatment adherence in PKU diminishes with age. Early
signs of treatment discontinuation can be identified during the second year of
life, allowing preventive interventions in high risk groups.
PMID- 28491817
TI - A 45,X/46,XY Male with Orchidopexy Diagnosed with Mixed Germ Cell Tumor After 21
year Follow-up.
AB - A case of a 45,X/46,XY boy with gonadal dysgenesis is presented. The patient
showed hypospadias and right undescended testis. He underwent underwent repair
surgery for hypospadias, right orchidopexy, and bilateral testicular biopsy.
Testicular biopsy revealed no malignant finding. He was followed-up annually by
scrotum palpation. When the patient grew up to 24 years old, he was diagnosed to
have right testicular tumor. High orchiectomy revealed pT1 seminoma. The
management of undescended testis in men with gonadal dysgenesis and disordered
sexual development is discussed.
PMID- 28491818
TI - Pancake Kidney Found Inside Abdominal Cavity: Rare Case with Literature Review.
AB - The cake or lump kidney is a rare form of fusion. The pancake kidney is always
found in the pelvic cavity, in the greater or lesser pelvis. However, we report a
case of pancake kidney which was found inside abdominal cavity while
investigating 32-year-old male for lower limb pain. CT scan with IV contrast
reveals 'fused mass situated in the right side of abdominal cavity with course
uncrossed ureters opening separately into the urinary bladder found incidentally
with patient work up'. Pancake kidney in this case was managed conservatively
without any complication. This malformation is usually present in pelvic cavity,
so blood supply is almost constant but in rare cases might be different and
follows location of this anomaly.
PMID- 28491819
TI - Optimization of prodigiosin production by Serratia marcescens using crude
glycerol and enhancing production using gamma radiation.
AB - Prodigiosin is a red pigment produced by Serratia marcescens. Prodigiosin is
regarded as a promising drug owing to its reported characteristics of possessing
anti-microbial, anti-cancer, and immunosuppressive activity. A factorial design
was applied to generate a set of 32 experimental combinations to study the
optimal conditions for pigment production using crude glycerol obtained from
local biodiesel facility as carbon source for the growth of Serratia marcescens.
The maximum production (870 unit/cell) was achieved at 22 degrees C, at pH 9
with the addition of 1% (w/v) peptone and 109 cell/ml inoculum size after 6 days
of incubation. Gamma radiation at dose 200 Gy was capable of doubling the
production of the pigment using the optimized conditions and manipulating
production temperature. Our results indicate that we have designed an economic
medium supporting enhanced Serratia marcescens MN5 prodigiosin production giving
an added value for crude glycerol obtained from biodiesel industry.
PMID- 28491820
TI - Endoplasmic Reticulum Stress, Unfolded Protein Response, and Cancer Cell Fate.
AB - Perturbation of endoplasmic reticulum (ER) homeostasis results in a stress
condition termed "ER stress" determining the activation of a finely regulated
program defined as unfolded protein response (UPR) and whose primary aim is to
restore this organelle's physiological activity. Several physiological and
pathological stimuli deregulate normal ER activity causing UPR activation, such
as hypoxia, glucose shortage, genome instability, and cytotoxic compounds
administration. Some of these stimuli are frequently observed during uncontrolled
proliferation of transformed cells, resulting in tumor core formation and stage
progression. Therefore, it is not surprising that ER stress is usually induced
during solid tumor development and stage progression, becoming an hallmark of
such malignancies. Several UPR components are in fact deregulated in different
tumor types, and accumulating data indicate their active involvement in tumor
development/progression. However, although the UPR program is primarily a pro
survival process, sustained and/or prolonged stress may result in cell death
induction. Therefore, understanding the mechanism(s) regulating the cell
survival/death decision under ER stress condition may be crucial in order to
specifically target tumor cells and possibly circumvent or overcome tumor
resistance to therapies. In this review, we discuss the role played by the UPR
program in tumor initiation, progression and resistance to therapy, highlighting
the recent advances that have improved our understanding of the molecular
mechanisms that regulate the survival/death switch.
PMID- 28491821
TI - Editorial: Exploring Cancer Metabolic Reprogramming through Molecular Imaging.
PMID- 28491822
TI - Comparison of the Expression Changes after Botulinum Toxin Type A and Minocycline
Administration in Lipopolysaccharide-Stimulated Rat Microglial and Astroglial
Cultures.
AB - Botulinum neurotoxin type A (BoNT/A) and minocycline are potent drugs used in
clinical therapies. The primary molecular mechanism of BoNT/A is the cleavage of
SNARE proteins, which prevents cells from releasing neurotransmitters from
vesicles, while the effects of minocycline are related to the inhibition of p38
activation. Both BoNT/A and minocycline exhibit analgesic effects, however, their
direct impact on glial cells is not fully known. Therefore, the aim of the
present study was to determine the effects of those drugs on microglial and
astroglial activity after lipopolysaccharide (LPS) stimulation and their
potential synergistic action. Our results show that BoNT/A and minocycline
influenced primary microglial cells by inhibiting intracellular signaling
pathways, such as p38, ERK1/2, NF-kappaB, and the release of pro-inflammatory
factors, including IL-1beta, IL-18, IL-6, and NOS2. We have revealed that, in
contrast to minocycline, BoNT/A treatment did not decrease LPS-induced release of
pro-inflammatory factors in the astroglia. In addition, BoNT/A decreased SNAP-23
in both types of glial cells and also SNAP-25 expressed only in astrocytes.
Moreover, BoNT/A increased TLR2 and its adaptor protein MyD88, but not TLR4
exclusively in microglial cells. Furthermore, we have shown the impact of BoNT/A
on microglial and astroglial cells, with a particular emphasis on its molecular
target, TLR2. In contrast, minocycline did not affect any of those factors. We
have revealed that despite of different molecular targets, minocycline, and
BoNT/A reduced the release of microglia-derived pro-inflammatory factors. In
conclusion, we have shown that BoNT/A and minocycline are effective drugs for the
management of neuroinflammation by dampening the activation of microglial cells,
with minocycline also affecting astroglial activity.
PMID- 28491823
TI - Comparative Proteomics Reveals Differences in Host-Pathogen Interaction between
Infectious and Commensal Relationship with Campylobacter jejuni.
AB - Campylobacter jejuni is the leading food-borne poisoning in industrialized
countries. While the bacteria causes disease in humans, it merely colonizes the
gut in poultry or pigs, where seems to establish a commensal relationship. Until
now, few studies have been conducted to elucidate the relationship between C.
jejuni and its different hosts. In this work, a comparative proteomics approach
was used to identify the underlying mechanisms involved in the divergent outcome
following C. jejuni infection in human and porcine host. Human (INT-407) and
porcine (IPEC-1) intestinal cell lines were infected by C. jejuni for 3 h (T3h)
and 24 h (T24h). C. jejuni infection prompted an intense inflammatory response at
T3h in human intestinal cells, mainly characterized by expression of proteins
involved in cell spreading, cell migration and promotion of reactive oxygen
species (ROS). Proteomic analysis evidenced significantly regulated biofunctions
in human cells related with engulfment and endocytosis, and supported by
canonical pathways associated to infection such as caveolar- and clathrin
mediated endocytosis signaling. In porcine IPEC-1 cells, inflammatory response as
well as signaling pathways that control cellular functions such as cell
migration, endocytosis and cell cycle progression resulted downregulated. These
differences in the host response to infection were supported by the different
pattern of adhesion and invasion proteins expressed by C. jejuni in human and
porcine cells. No marked differences in expression of virulence factors involved
in adaptive response and iron acquisition functions were observed. Therefore, the
results of this study suggest that both host and pathogen factors are responsible
for commensal or infectious character of C. jejuni in different hosts.
PMID- 28491824
TI - Rabies Virus Infection Induces Microtubule Depolymerization to Facilitate Viral
RNA Synthesis by Upregulating HDAC6.
AB - Rabies virus (RABV) is the cause of rabies, and is associated with severe
neurological symptoms, high mortality rate, and a serious threat to human health.
Although cellular tubulin has recently been identified to be incorporated into
RABV particles, the effects of RABV infection on the microtubule cytoskeleton
remain poorly understood. In this study, we show that RABV infection induces
microtubule depolymerization as observed by confocal microscopy, which is closely
associated with the formation of the filamentous network of the RABV M protein.
Depolymerization of microtubules significantly increases viral RNA synthesis,
while the polymerization of microtubules notably inhibits viral RNA synthesis and
prevents the viral M protein from inducing the formation of the filamentous
network. Furthermore, the histone deacetylase 6 (HDAC6) expression level
progressively increases during RABV infection, and the inhibition of HDAC6
deacetylase activity significantly decreases viral RNA synthesis. In addition,
the expression of viral M protein alone was found to significantly upregulate
HDAC6 expression, leading to a substantial reduction in its substrate, acetylated
alpha-tubulin, eventually resulting in microtubule depolymerization. These
results demonstrate that HDAC6 plays a positive role in viral transcription and
replication by inducing microtubule depolymerization during RABV infection.
PMID- 28491825
TI - HCMV activation of ERK-MAPK drives a multi-factorial response promoting the
survival of infected myeloid progenitors.
AB - Viral binding and entry provides the first trigger of a cell death response and
thus how human cytomegalovirus (HCMV) evades this - particularly during latent
infection where a very limited pattern of gene expression is observed - is less
well understood. It has been demonstrated that the activation of cellular
signalling pathways upon virus binding promotes the survival of latently infected
cells by the activation of cell encoded anti-apoptotic responses. In CD34+ cells,
a major site of HCMV latency, ERK signalling is important for survival and we now
show that the activation of this pathway impacts on multiple aspects of cell
death pathways. The data illustrate that HCMV infection triggers activation of
pro-apoptotic Bak which is then countered through multiple ERK-dependent
functions. Specifically, ERK promotes ELK1 mediated transcription of the key
survival molecule MCL-1, along with a concomitant decrease of the pro-apoptotic
BIM and PUMA proteins. Finally, we show that the elimination of ELK-1 from CD34+
cells results in elevated Bak activation in response to viral infection,
resulting in cell death. Taken together, these data begin to shed light on the
poly-functional response elicited by HCMV via ERK-MAPK to promote cell survival.
PMID- 28491826
TI - Acellular pertussis vaccine efficacy: An updated systematic review and meta
analysis.
AB - Background: Recent studies indicate an increased incidence of pertussis disease
in recent years. The aim of this study was to evaluate the efficacy of the
acellular vaccine for children (as a replacement of current whole cell vaccine in
the Expanded Program on Immunization) and for high-risk adults in Iran through
updating current best available evidence. Methods: We performed a systematic
literature review in relevant databases we focused on previously published
systematic reviews to select those that address our questions. The AMSTAR
(assessing the methodological quality of systematic reviews) tool was used for
screening available reviews. Then search in databases was done until Feb 2014 to
update the evidence. We pooled results using meta-analysis methods by Stata
statistical package. Results: Eleven systematic review articles were included in
the initial evaluation. In the end, two systematic reviews on acellular vaccine
booster doses and the acellular vaccine in children were selected as the baseline
evidence. In the update phase, new clinical trials were screened, and the results
were updated. Overall pooled estimate of relative efficacy of acellular to whole
cell was 0.68 (95% CI, 0.55-0.81) for children immunization Pooled estimates for
the efficacy of acellular versus placebo were 0.70 (95% CI, 0.60-0.80). Overall
pooled estimate of efficacy of booster dose of acellular was 0.87(95% CI, 0.85
0.88) compared to placebo. In addition pooled estimate of acellular vaccine
efficacy based on response to antigen was 0.78(95% CI, 0.64-0.93) in highrisk
group. Conclusion: The results show higher performance and safety of the
acellular vaccine in the prevention of pertussis in children versus the whole
cell vaccine. Moreover, the efficacy of the acellular vaccine in high-risk adult
groups is acceptable. This study provides evidence in favor of the introduction
of an acellular vaccine to the national program of immunization. Studies on cost
effectiveness and aspects of policy analysis are recommended.
PMID- 28491827
TI - Effect of exercise training on saliva brain derived neurotrophic factor, catalase
and vitamin c.
AB - Background: The balance between production of Reactive Oxygen Species (ROS) and
antioxidant defense in the body has important health implications. The aim of
this study was to investigate the changes in salivary antioxidants: catalase,
vitamin C and brain-derived neurotrophic factor (BDNF), in sedentary men at rest
and after acute exhaustive exercise. Methods: This randomized controlled clinical
trial (The registry code IRCT2011053212431N1) recruited twenty-five sedentary men
(age=21+/-3yrs; height=172+/-8cm; weight=66+/-9kg; VO2 max=37.6+/-7.4mL*kgkg
1*min-1) participated in a double-blind randomized experiment. Unstimulated whole
saliva samples were collected before, immediately and 1 hour after exhaustive
treadmill running. Catalase, vitamin C (Vit C) concentration, and BDNF
concentrations were determined using biochemical assays and ELISA respectively.
Repeated measures ANOVA and Bonferroni posthoc test were used to analyze data.
Results: The results of the present study showed that an acute intensive exercise
causes a reduction in salivary catalase, Vit C and also BDNF concentration
(p<0.05) compared with pre-exercise. Both catalase and Vit C showed a tendency to
return to pre-exercise value after one hour. However, BDNF continued to reduction
at least 1 hour after the ending of the training. Conclusion: Reduction in
antioxidants capacity of saliva might reflects disturbance in natural antioxidant
defense mechanisms of the body after an acute intensive physical stress and
possible further health threatening consequences.
PMID- 28491828
TI - The association between fear of falling and quality of life for balance
impairments based on hip and ankle strategies in the drug On- and Off-phase of
patients with idiopathic Parkinson' disease.
AB - Background: Despite the negative effect of fear of falling during functioning and
social participation of patients with Parkinson' disease, so far, only few
studies have investigated its effect on the quality of life in these patients. We
aimed to investigate the association between fear of falling and quality of life
controlling for balance impairments based on hip and ankle strategy in drug On-
and Off-phase of patients with idiopathic Parkinson' disease. Methods: In this
non-experimental cross-sectional study, 139 patients with idiopathic Parkinson'
disease (100 male, 39 female) by mean+/- SD age of 60.2+/-12.27 years, mean+/-SD
time since diagnosis of 6.7+/-5.53 years and mean+/-SD Hoehn and Yahr stage of
2.8+/-1.49 were selected by a simple non-probability method. Balance function was
measured by a functional reach test with hip and ankle strategy. The Persian
version of the selfcompleted Fall Efficacy Scale-International and Parkinson's
disease quality of life questionnaire was used to evaluate fear of falling and
quality of life, respectively. Results: The results showed that the score of all
dimensions of quality of life (i.e., mobility, activities of daily living,
emotional wellbeing, stigma, social support, cognition, communication and bodily
discomfort) were significantly affected by the intensity of fear of falling.
Multiple regression analysis indicated a significant association between fear of
falling and quality of life in a way that fear of falling explained 11% to 47%
and 12% to 43% of variance in drug On-phase, as well as 8% to 45% and 9% to 48%
of variance in the drug Off-phase in dimensions of quality of life after
controlling for balance function based on hip and ankle strategy, respectively.
In the drug On-phase, the strongest association (R=0.85, p<0.001) was found
between fear of falling and mobility dimension of quality of life. In the drug
Off-phase, the strongest relation was observed between fear of falling and
mobility (R=0.82, p<0.001) as well as activities of daily living (R=0.78-0.79,
p<0.001) dimensions. Conclusion: This study found that fear of falling affects
the quality of life of patients with Parkinson' disease beyond its relationship
with balance impairments based on the hip and ankle strategy in both drug On- and
Off-phase.
PMID- 28491829
TI - Assessment of nutritional status in patients with Parkinson's disease and its
relationship with severity of the disease.
AB - Background: Malnutrition, loss of body weight, muscle and fat mass wasting are
common in patients with Parkinson's disease, and are associated with disability,
longer length of hospital stay, impaired immune system and increased risk of
mortality. The aim of this study was to assess the nutritional status in patients
with Parkinson's disease and its relation to the severity of the disease.
Methods: This cross- sectional study was conducted on 130 patients with
Parkinson's disease, with a mean (SD) age of 59.1 (12.9) years in disease stages
of 1 to 4. In this study, the Mini Nutritional Assessment (MNA) questionnaire was
used along with anthropometric measurements (Body Mass Index (BMI), Mid-arm
circumference (MAC), Calf Circumference (CC)) to evaluate the nutritional status,
and they were applied by a trained nutritionist. Hoehn and Yahr Scale were used
to determine the severity of the disease. One-way ANOVA test was used to assess
the relationship between anthropometric indices, nutritional status and severity
of disease. Assessment of the relationship between age, duration of disease and
nutritional status was categorized according to MNA score, and was performed,
using one-way ANOVA. Chi - Square test was utilized to assess the relationship
between education level and nutritional status. SPSS Version 18 was used for data
analysis. Results: In this study, 30% (n=39) of the participants were diagnosed
with normal nutritional status, 58.5% (n=76) were at risk of malnutrition and
11.5% (n=15) were malnourished according to MNA. Reduction of weight, and muscle
mass wasting was observed in different disease stages. Muscle mass wasting and
worsening nutritional status, based on MNA score, showed a significant increase
as the disease progressed, MAC (p=0.009), MNA score (p<0.001). After assessing
the relationship between education level, age, duration of disease with
nutritional status, the results revealed a significant relationship between age
(p=0.008), education level (p<0.001) with nutritional status according to MNA
score. Conclusion: Reduction of BMI, depletion of muscle mass, and worsening of
nutritional status according to MNA, was observed in many patients along with an
increase in the severity of the disease. Assessing nutritional status in those
with Parkinson's disease to provide information to identify necessary nutritional
intervention is highly recommended.
PMID- 28491830
TI - Designing and assessing fixed dental prostheses 2 multimedia-based education in
dentistry students.
AB - Background: Above all methods effective learning results from decent training,
acquired in the proper environment and encouraging creative methods. Computer
assisted training by educational software is considered a fundamental measure to
improve medical and dentistry education systems. This study aims to design and
assess fixed dental prostheses via 2 multimedia instructional contents at the
Guilan dentistry school. Methods: This is a descriptive and cross-sectional
study. First off, the instructional content was analyzed. The software used to
produce multimedia was the iSpring suite Ver.7.0. After designing the
instructional multimedia, this software was loaded by LMS. Sixty-nine dentistry
students in the 5th semester at Guilan Dentistry School were selected via
convenience sampling. At the end of the course, a structured questionnaire
containing 26 items were handed to the students to evaluate the instructional
multimedia quality. Results: Mean +/-SD age was 24.68+/-3.24 years, 43 were women
(62.4%) and 26 were men (37.6%) -the majority of 76.8% used the internet at home.
A portion of 33.3% were inclined to use multimedia and the internet with in
person training. About 60% declared that multimedia quality as being good.
Conclusion: the instructional multimedia designs which are compatible with lesson
objectives and audiovisual facilities can have a great effect on the student's
satisfaction. Preparing instructional multimedia makes the instructional content
easily accessible for students to be able to review it several times at the
proper opportunity and if presented through LMS they would be able to study the
lesson subject wherever and whenever accessing the internet.
PMID- 28491831
TI - The effect of an android-based application on the knowledge of the caregivers of
children with cerebral palsy.
AB - Background: Mobile health and e-learning may have a significant impact on
training patients, physicians, students and caregivers. This study aimed to
evaluate the effect of using an educational mobile application on the knowledge
of the caregivers of children with cerebral palsy (CP). Methods: We used a
previously developed mobile application. The knowledge of 17 caregivers of
children with CP (including parents) about the daily care of their children was
evaluated through a self-assessment and a test with multiple-choice and true
false questions. Next, the application, which included several educational
modules for the daily care of the children with CP, was given to the caregivers
to use continually for two months. After this period, the knowledge of the
caregivers was evaluated by the same tools. Data analysis was performed by SPSS
16, using paired-sample t-test or Wilcoxon test. Results: The effect of the use
of this educational application on the knowledge of caregivers in all childcare
domains, except for eating, was reported to be significant (p<0.05). Furthermore,
the results of the multiplechoice test revealed that this application increased
the knowledge of caregivers in all domains except playing (p<0.05). Conclusion:
Training through novel technologies such as Smartphone along with their
applications can improve the knowledge of caregivers about the daily care of
children with cerebral palsy.
PMID- 28491832
TI - Factors influencing the adoption of E-learning in Tabriz University of Medical
Sciences.
AB - Background: Electronic Learning (E-learning), is the use of electronic technology
in education via computer and the internet. Despite its slow adoption by faculty
members, e-learning provides several benefits to individuals and organizations.
This study was conducted to determine the factors influencing the adoption of e
learning by faculty members in Tabriz University of Medical Sciences. Methods:
This was a cross- sectional study, in which a sample of 190 faculty members of
Tabriz University of Medical Sciences was randomly selected, using stratified
sampling. A Conceptual Path Model of Unified Theory of Acceptance and Use of
Technology (UTAUT) was applied to assess the faculty members' attitude towards e
learning. The collected data were analyzed by SPSS16, using descriptive
statistics and regression analysis. The model was tested by structural equation
modeling (SEM) and was finally represented by Analysis of Moment Structures.
Results: The results evidenced that UTAUT model explains about 56% of the
variance for adoption of elearning. The findings also revealed that performance
expectancy, effort expectancy, social influences and behavior indentation had
direct and significant effects on faculty members' behavior towards the use of e
learning. However, facilitated condition had no significant effects on the use of
e-learning. Conclusion: The authorized model provides considerable insight for
perception and anticipation of faculty members' behaviors in adopting e-learning.
The survey clearly identified significant and non-significant factors that may
affect the adoption of e-learning. The results of this study could help the
policy makers when successful adoption of e-learning is in their agenda.
PMID- 28491833
TI - Virtual in-service training from the librarians' point of view in libraries of
medical sciences universities in Tehran.
AB - Background: In-service training courses are one of the most available programs
that are used to improve the quantity and quality level of the staff services in
various organizations, including libraries and information centers. With the
advent of new technologies in the field of education, the problems and
shortcomings of traditional in-service training courses were replaced with
virtual ones. This study aimed to evaluate the virtual in-service training
courses from the librarians' point of view in libraries of state universities of
medical sciences in Tehran. Methods: This was a descriptive- analytical study.
The statistical population consisted of all librarians at libraries of
universities of medical sciences in Tehran. Out of 103 librarians working in the
libraries under the study, 93 (90%) participated in this study. Data were
collected, using a questionnaire. Results: The results revealed that 94/6% of
librarians were satisfied to participate in virtual in-service training courses.
In this study, only 45 out of 93 participants said that the virtual in-service
courses were held in their libraries. Of the participants, 75.6% were satisfied
with the length of training courses, and one month seemed to be adequate time
duration for the librarians to be more satisfied. The satisfaction level of the
individuals who participated in in-service courses of the National Library was
moderate to high. A total of 84.4% participants announced that the productivity
level of the training courses was moderate to high. The most important problem
with which the librarians were confronted in virtual in-service training was the
"low speed of the internet and inadequate computer substructures". Conclusion:
Effectiveness of in-service training courses from librarians' point of view was
at an optimal level in the studied libraries.
PMID- 28491834
TI - systematized review of telemedicine applications in treating burn patients.
AB - Background: Telemedicine has been used in different fields of medicine in the
past 20 years. The main advantages of this technology include saving costs,
improving quality of care, and increasing access to specialists. This study aimed
to review telemedicine applications in treating burn patients. Methods: In this
systematized review study, related papers were searched using various databases,
including PubMed, Scopus, and Science Direct. The time frame was between January
2000 and March 2016; finally, 32 papers were included in the study. Results: The
findings revealed that telemedicine was used in burn care in three different
ways: Remote patient follow-up, teleconsultation, and patient assessment.
Conclusion: It seems that telemedicine can be easily applied in treating burn
patients even when there is a limited financial resource. The use of this
technology can help reduce possible errors in categorizing burn patients and
decrease patients' transportation and treatment costs.
PMID- 28491835
TI - Evaluation of the learning management system using students' perceptions.
AB - Background: Learning Management System (LMS) is a web-based system designed to
support teaching and learning at an institution. The capabilities of any LMS are
required to be evaluated to detect the room for improvement. This study aimed at
discovering the students' perceptions of the functions of the LMS at Iran
University of Medical Sciences (IUMS). Methods: This qualitative study included
15 students of two master programs of Biostatistics and Medical Librarianship
during the fall semester of 2015. The participants were asked to write down their
perceptions of the experiences they had while using the LMS and classify them
based on two categories of "Advantages and Drawbacks". Framework Analysis
technique was used to analyze the views. Results: The themes emerging from the
'Advantages' included advantages for the students, advantages for the teachers,
and advantages for both; however, those from the 'Drawbacks' were found to be
technical and nontechnical problems. Conclusion: The major debated points in the
comments comprised the students' positive accounts of the Forum section, and
their complaints of the frequent glitches recurring in the system as well as some
constructive problems such as inefficient tools for typing in English. Some all
inclusive inferences concerning the methodology of the study have also been
pointed out in the final section.
PMID- 28491836
TI - Three-dimensional simulation of human teeth and its application in dental
education and research.
AB - Background: A comprehensive database, comprising geometry and properties of human
teeth, is needed for dentistry education and dental research. The aim of this
study was to create a three-dimensional model of human teeth to improve the
dental E-learning and dental research. Methods: In this study, a cross-section
picture of the three-dimensional model of the teeth was used. CT-Scan images were
used in the first method. The space between the cross- sectional images was about
200 to 500 micrometers. Hard tissue margin was detected in each image by Matlab
(R2009b), as image processing software. The images were transferred to Solidworks
2015 software. Tooth border curve was fitted on B-spline curves, using the least
square-curve fitting algorithm. After transferring all curves for each tooth to
Solidworks, the surface was created based on the surface fitting technique. This
surface was meshed in Meshlab-v132 software, and the optimization of the surface
was done based on the remeshing technique. The mechanical properties of the teeth
were applied to the dental model. Results: This study presented a methodology for
communication between CT-Scan images and the finite element and training software
through which modeling and simulation of the teeth were performed. In this study,
cross-sectional images were used for modeling. According to the findings, the
cost and time were reduced compared to other studies. Conclusion: The three
dimensional model method presented in this study facilitated the learning of the
dental students and dentists. Based on the three-dimensional model proposed in
this study, designing and manufacturing the implants and dental prosthesis are
possible.
PMID- 28491837
TI - Incorporating E-learning in teaching English language to medical students:
exploring its potential contributions.
AB - Background: The spread of technology has influenced different aspects of human
life, and teaching and learning are not exceptions. This study aimed to examine
the potential contribution of the use of technology in teaching English language
to medical students. Methods: This qualitative-action research study was
conducted in Birjand University of Medical Sciences (BUMS), with 60 medical
students taking a general English course in the Fall Semester of 2015. The class
favored different tools and multimedia facilities such as a tube channel, e
dictionaries, educational films, and etextbooks to enhance students' learning. In
addition, the class had a weblog in which students could upload assignments and
receive feedback from peers and the instructors. Results: The results revealed
that e-learning could enhance students' language proficiency and facilitate the
teaching process. Learners preferred to use more e-dictionaries to learn the
meaning of the new words, watch English medical films to boost their speaking and
listening skills, and use the electronic version of their textbook as they could
carry it wherever they wanted. Conclusion: The students preferred this method of
learning English as they became more independent by using the electronic
facilities. They found that learning English did not have a fixed
institutionalized method, and e-learning activities could provide them with
authentic input for language learning even outside of the classroom.
PMID- 28491838
TI - The essential skills required by librarians to support medical virtual learning
programs.
AB - Background: With the recent spread of virtual learning programs in universities,
especially in the field of medical sciences, libraries play a crucial role to
support these programs. This study aimed at investigating the skills required by
librarians to support virtual learning programs in Isfahan University and Isfahan
University of Medical Sciences. Methods: This was an applied survey study. The
population of the study includes all librarians working in Isfahan University and
Isfahan University of Medical Sciences. A sample of 89 librarians was selected by
stratified random sampling. Data were collected by a researcher-made
questionnaire, the validity of which was confirmed by specialists in the fields
of librarianship and information sciences and virtual learning, and its
reliability was determined to be 0.92, using Cronbach's Alpha. The questionnaire
consisted of 51 items designed to evaluate the librarians' virtual learning
skills using Likert scale. Descriptive and inferential statistics were used to
analyze the findings. Results: The findings of this study revealed that
librarians had low level of skills with respect to the online reference services,
and familiarity with virtual learning environment. They also showed low and
average level of skills with respect to their general information technology,
communication skills, ability to teach electronic information literacy and
ability to create access to electronic resources. The results revealed no
significant difference between the librarians of the two universities, or between
male and female librarians. However, librarians with educational background in
librarianship and information sciences were significantly more skillful and
competent than their colleagues. Conclusion: Despite the crucial role of
libraries in supporting virtual learning programs, the librarians in Isfahan
University and Isfahan University of Medical Sciences had low-level skills to
play such an important role. Therefore, it is essential to provide on-the-job
virtual training courses for librarians to improve their job performance and the
quality of library services.
PMID- 28491839
TI - Online survey software as a data collection tool for medical education: A case
study on lesson plan assessment.
AB - Background: There are no general strategies or tools to evaluate daily lesson
plans; however, assessments conducted using traditional methods usually include
course plans. This study aimed to evaluate the strengths and weaknesses of online
survey software in collecting data on education in medical fields and the
application of such softwares to evaluate students' views and modification of
lesson plans. Methods: After investigating the available online survey software,
esurveypro was selected for assessing daily lesson plans. After using the
software for one semester, a questionnaire was prepared to assess the advantages
and disadvantages of this method and students' views in a cross-sectional study.
Results: The majority of the students (51.7%) rated the evaluation of classes per
session (lesson plans) using the online survey as useful or very useful. About
51% (n=36) of the students considered this method effective in improving the
management of each session, 67.1% (n=47) considered it effective in improving the
management of sessions for the next semester, and 51.4% (n=36) said it had a high
impact on improving the educational content of subsequent sessions. Finally,
61.4% (n=43) students expressed high and very high levels of satisfaction with
using an online survey at each session. Conclusion: The use of online surveys may
be appropriate to improve lesson plans and educational planning at different
levels. This method can be used for other evaluations and for assessing people's
opinions at different levels of an educational system.
PMID- 28491840
TI - The relationship between hospital managers' leadership style and effectiveness
with passing managerial training courses.
AB - Background: Effective leadership that rises from managerial training courses is
highly constructive in managing hospitals more effectively. This study aims at
investigating the relationship between leadership effectiveness with providing
management training courses for hospital managers. Methods: This was a cross
sectional study carried out on top and middle managers of 16 hospitals of Iran
University of Medical Sciences. As a sample, 96 participants were selected
through census method. Data were collected using leadership effectiveness and
style questionnaire, whose validity and reliability were certified in previous
studies. Pearson correlation coefficient and linear regressions were used for
data analysis. Results: Leadership effectiveness score was estimated to be 4.36,
showing a suitable status for managers' leadership effectiveness compared to the
set criteria. No significant difference was found between leadership
effectiveness and styles among managers who had passed the training courses with
those who had not (p>0.05). Conclusion: Passing managerial training courses may
have no significant effect on managers' leadership effectiveness, but there may
be some other variables which should be meticulously studied.
PMID- 28491841
TI - The effect of foot hyperpronation on spine alignment in standing position.
AB - Background: According to clinical observations, foot hyperpronation is very
prevalent and may cause malalignment of the lower extremity, leading to
structural and functional deficits in standing and walking. This study aimed at
investigating the effect of foot hyperpronation on spine alignment in the
standing position. Methods: Thirty-five healthy males with an age range of 18-30
years participated in this cross-sectional study. Evaluation was performed with
two examiners in four standing positions (on the floor, and on the wedges angled
at 10, 15, and 20 degrees) using a motion analysis system (Zebris). Moreover,
each of the measurement methods was repeated for three short times. Paired t-
test and repeated measures ANOVA test were used for statistical analysis.
Results: Significant differences were observed between all modes in the sacral
angle, pelvic inclination, lumbar lordosis, and thoracic kyphosis variables
(except between the first and second mode). Finally, a positive correlation was
obtained for the examiners and all the variables with an increasing slope of the
angle of wedge. Conclusion: The results of the present study revealed sacral
angle, pelvic inclination, lumbar lordosis, and thoracic kyphosis were increased
with an increase in bilateral foot pronation. In fact, each one of them is a
compensatory phenomenon.
PMID- 28491842
TI - Ergonomic risk factors and musculoskeletal symptoms in surgeons with three types
of surgery: Open, laparoscopic, and microsurgery.
AB - Background: Musculoskeletal symptoms are the main cause of loss of working time,
and increase in labor costs. Poor posture is the most important risk factor for
work-related musculoskeletal symptoms. This study aimed at evaluating the role of
ergonomic risk factors in different surgical (open surgery, laparoscopy, and
microsurgery) in the frequency or resonance frequency of musculoskeletal
symptoms. Methods: This descriptive-analytic study was conducted on 81 surgeons
in a hospital in Tehran. In this study, the prevalence of musculoskeletal
symptoms was evaluated using the Nordic Questionnaire. Moreover, Workplace
ergonomic risk assessment method (WERA) was used to evaluate ergonomic risk
factors in 3 types of open surgery, laparoscopy, and microsurgery. Results: The
results revealed that the prevalence of musculoskeletal symptoms of the neck,
back, shoulder, and arm is high in surgeons (over 75%). The mean final score of
WERA was 40.11, representing the high risk of the 3 types of surgery for the
prevalence of musculoskeletal symptoms. Results revealed that the prevalence of
musculoskeletal symptoms in the neck, waist and wrists had a significant
relationship with the body posture in the 3 types of open surgery, laparoscopy,
and microsurgery (p<0.05). Conclusion: In the present study, the prevalence of
musculoskeletal symptoms was high in the neck, waist, and hands surgeries.
Depending on the type of surgery, teaching correct working methods, using proper
seats and ergonomic equipment are the best strategies to reduce musculoskeletal
symptoms in the surgical profession.
PMID- 28491843
TI - Evaluation of occupational allergic contact dermatitis and its related factors in
Iran.
AB - Background: Occupational contact dermatitis, especially in hand, is one of the
most common occupational disorders. The present study aimed at evaluating
patients with occupational allergic contact dermatitis (ACD) caused by common
allergens based on occupation type and disease history. Methods: This cross
sectional study aimed at evaluating the data of the patients with probable
diagnosis of ACD in Center for Research and Training in Skin Diseases and Leprosy
(CRTSDL) in Iran. In the present study, 946 patients were assessed from different
regions of Iran. One hundred fifty-one cases with positive patch test and
relevant exposure were entered into the study; data related to their occupation
and disease activity history were evaluated and recorded. Then, factors related
to disease activity history were assessed considering the occupational groups and
common exposures. Results: Nickel sulphate was the most common allergen in the
151 patients. Disease activity was constant in 29.8% of the patients; it
increased in 27.8%, and decreased just before doing the patch test in 42.4%. Of
the patients, 52.3% were getting worse during the working days. Occupational
groups were significantly different in age and gender. Disease duration was also
different in the occupational groups (p=0.001). The least disease duration was
observed in healthcare workers, and the most in service workers. Lesions in the
foot were related to period of employment. In administrative work group,
(teachers, technicians and housewives) disease activity was decreased in the most
cases, while it was increased in most patients of service workers (p=0.086).
Conclusion: The present study, similar to previous reports, revealed that nickel
sulphate is the most common allergen in ACD cases. Moreover, it was found that
the symptoms of disease activity remained constant or increased in a significant
proportion of the cases during the working days. Therefore, these workers should
seriously follow up on this matter and change their occupation, or limit the
exposure to allergens.
PMID- 28491844
TI - Factors associated with the severity of fatal accidents in construction workers.
AB - Background: Construction work (building houses, roads, workplaces, and repairing
and maintaining infrastructures) is a dangerous land-based job. This includes
many hazardous tasks and conditions such as working at the following conditions:
Height, excavation, noise, dust, power tools and equipment. Construction work has
been increased in developed and underdeveloped countries over the past few years.
Occupational fatalities have increased with an increase in this type of work.
Occupational fatalities refer to individuals who pass way while on the job or
performing work related tasks. In the present study, to identify the factors,
personal characteristics and work-related factors associated with fatal
occupational mortality were assessed using data for Tehran, Iran, 2014-2016.
Methods: We conducted a retrospective study, using 967 postmortem reports from
fatal occupational injuries collected through postmortem investigations during
2014-2016. A sampling frame of 967 postmortem reports from fatal occupational
injuries was used to draw a total sample of 714 fatal construction accidents for
this cross-sectional study. Pearson chi2 test and Kruskal-Wallis tests were used
for statistical analysis. Results: Based on the results of this study, male
gender (n=714; 100%), age range of 30-39 years (n=183; 25.6%), secondary
educational level (n=273; 38.2%), being married (317; 44.4%), causal employee
(n=389; 54.5%), unskilled performance (389; 54.5%), no insurance coverage (472;
66.1%), and daytime duty work (287; 40.2%) were identified as risk factors for
fatality in the event of construction fatal injury. A significant relationship
was found between the type of injury and sociodemographic and work related
variables. Conclusion: Workers' characteristics such as age, gender, experience,
and educational background, and work related variables such as skill training,
safety measurement, and close monitoring could be used to discriminate among
different severity levels of occupational fatal accidents.
PMID- 28491845
TI - The role of work- related physical and psychological factors on prevalence of
neck/shoulder complaints among nurses: A multicentric study.
AB - Background: Identifying the predisposing factors of neck and shoulder complaints
and finding solutions to avoid them could improve the occupational health
condition of the nurses. In this study, we aimed at determining the role of
psychological and physical occupational factors in developing neck and shoulder
complaints among the participants. Methods: This analytic cross-sectional study
was conducted on the nurses of main hospitals of Tehran. To study the prevalence
of neck and shoulder pain, the Nordic questionnaire was used, and job content
questionnaire was used to assess the psychological and physical occupational
factors. Data were analyzed using SPSS and statistical methods. Independent
sample t-test was used to compare the qualitative variables, and chi-square test
was utilized for the statistical analysis of the qualitative variables. Results:
Prevalence of neck and shoulder complaints among the nurses with high physical
workload was significantly higher than in those nurses with low physical
workload. Unlike physical workload, the prevalence of neck and shoulder
complaints was not significantly different between the nurses with low or high
psychological workload. Prevalence of neck and shoulder complaints among the
female nurses was significantly higher than in the male nurses. In our study,
only female nurses with high physical workload had been known as independent
predictors of neck and shoulder complaints. Conclusion: Those nurses who had more
workload, especially physical workload, had a higher prevalence of neck and
shoulder complaints, and this fact could affect their work tasks.
PMID- 28491846
TI - The effect of work- related stress on development of neck and shoulder complaints
among nurses in one tertiary hospital in Iran.
AB - Background: There are some challenges about the role of work- related stress on
development of musculoskeletal complaints. The present prospective study was
conducted on nurses of Milad hospital in Tehran (Iran) to assess the role of work
related stress on development of neck and shoulder pain among nurses. Methods:
From the 1,900 nurses who completed the registry forms, 1,450 nurses met the
inclusion criteria. We divided the participants into exposed and unexposed groups
according to their DASS-21 scores. We collected the data of neck and shoulder
pain among the nurses at two points of the first and the second year after the
study, using the Nordic Questionnaire. Qualitative and quantitative variables
were compared between the exposed and unexposed variables with chi-square and
independent sample t-test, respectively. Results: One year after the commencement
of the study, 62 (9.1%) nurses in the exposed group and 36 (4.7%) in the
unexposed group had been reported as new cases of neck and shoulder pain,
respectively. The incidence of the new cases of neck and shoulder pain was
significantly higher in the exposed group compared to the unexposed group (p=
0.001). Two years after the start of the study, at the second follow-up point,
135 (19.8%) nurses in the exposed group and 76 (9.9%) in the unexposed group had
been reported as new cases of neck and shoulder pain, respectively. The incidence
of new cases of neck and shoulder pain was significantly higher in the exposed
group compared to the unexposed group (p<0.001). Conclusions: The incidence of
neck and shoulder pain was higher in those nurses with high level of workrelated
stress. According to our results, more attention should be paid to mental health
as well as physical symptoms and limitations of the healthcare workers when they
refer to occupational health services with musculoskeletal pain complaints.
PMID- 28491847
TI - The effect of a multifaceted ergonomic intervention program on reducing
musculoskeletal disorders in dentists.
AB - Background: Work-related musculoskeletal disorders (WMSDs) are the most common
occupational injuries in dentists. These disorders occur due to the specific
characteristics of dentistry occupation such as the use of tools and instruments
and awkward posture. The present study aimed at evaluating the effect of
multifaceted ergonomic program on reducing musculoskeletal disorders in dentists.
Methods: One hundred-two male dentists who worked in dentistry clinics of
Tehran's hospitals participated in this interventional study. Participants were
randomly divided into control (n=50) and intervention (n=52) groups. Dentists in
the intervention group (n=52) underwent multifaceted ergonomic intervention
program for 8 weeks and dentists in the control group (n=50) only received the
measurements. The prevalence of musculoskeletal disorders was evaluated in each
of the 2 groups at 3 time points before the intervention, 3, and 6 months after
the intervention using the Nordic Musculoskeletal Questionnaire (NMQ). Paired t
test was used to compare the prevalence of musculoskeletal disorders before and
after the ergonomic intervention program at the end of 3 and 6 months. Results:
The results revealed that the prevalence of musculoskeletal disorders was reduced
after the intervention in the neck, shoulder, arm, wrist, back, thigh, knees, and
feet (p<0.05). On the other hand, the prevalence of musculoskeletal disorders
increased in the control group in the neck, shoulder, arm, wrist, thigh, and
knee, respectively. The survey results revealed that 98% of the participants
agreed with this intervention program. Conclusion: The results of this study
revealed that the multifaceted ergonomic intervention program, which included
improving working conditions, identifying ergonomic risk factors, regular
exercise, and discussion group meetings, could decrease the prevalence of
musculoskeletal disorders in dentists.
PMID- 28491848
TI - The effect of magnification lenses on reducing musculoskeletal discomfort among
dentists.
AB - Background: Work-related musculoskeletal disorders are the most important
problems in the health workforce. These discomforts cause many working days
losses, increase absenteeism from work, and impose annual economic costs. Awkward
posture is the most important factor among the risk factors for work-related
musculoskeletal disorders. This study aimed at implementing an interventional
ergonomic program to minimize musculoskeletal disorder among dentists. Methods:
This semi- experimental study was conducted on 75 dentists of Milad hospital
using a census method. The Nordic Questionnaire was used to determine the
prevalence of musculoskeletal disorders. In this study, the intervention was to
apply optical magnification lens whose impact on reducing musculoskeletal
disorder had been previously investigated. Corlett and Bishop Scale was used to
evaluate musculoskeletal disorders before and after the intervention. Paired t
test was conducted to compare the discomfort intensity before and after the
intervention. Results: The results revealed that the prevalence of
musculoskeletal disorders in neck, back, shoulder, and arm were higher than other
areas of the body in dentists. There was a significant difference in discomfort
intensity of the neck, shoulder, arm, back, elbow, forearm, and the whole body
after the ergonomic intervention (p<0.05). Surveys on improving working
conditions using the magnification lens revealed that more than 89% of the
individuals expressed that the use of the lens increased the ease while working.
Conclusion: The present study revealed that the use of optical magnification
loupes, because of providing a suitable posture while working, could reduce
musculoskeletal disorders in different areas of the body. Thus, we can predict
that the prevalence of musculoskeletal disorders will be reduced in dentists in a
long run if they use optical magnification loupes.
PMID- 28491849
TI - Work-related stress and quality of life among Iranian blue-collar workers with
self-reported low back pain.
AB - Background: Impairment in quality of life and mental health had been reported in
the previous studies as the results of musculoskeletal disorders among workers.
Mental health has a wide concept and contains different disorders including
anxiety, depression or even decreased quality of life, all of which having
challengeable impacts on work- related characters such as work productivity and
absensism. The present study aimed at evaluating work- related stress and quality
of life among Iranian blue-collar workers of Fars ABFA Company with selfreported
low back pain. Methods: In the present study, we focused on the low back pain
among 451 blue-collar workers and assessed their work- related stress and quality
of life status using DASS-21 and short form questionnaire (SF-36), respectively.
Independent sample t-test was used to compare the qualitative variables, and chi
square test was utilized for statistical analysis of the qualitative variables.
Results: Mean of the total score of quality of life among workers with low back
pain was significantly lower than in those workers without low back pain. The
mean of work- related stress score was significantly higher in workers with low
back pain than in workers without low back pain. The mean quality of life
subdomains in patients with low back pain was significantly lower than in workers
without low back pain. Conclusion: Findings of the present study revealed that
workers with low back pain had lower quality of life score and higher work-
related stress score. These findings should be considered in designing preventive
programs rather than controlling the pain.
PMID- 28491850
TI - MicroRNAs as biomarkers associated with bladder cancer.
AB - Bladder cancer is the fifth most common cancer with significant morbidity and
mortality. Recently, numerous studies demonstrated that microRNAs are emerging as
diagnostic biomarkers for bladder cancer. Specific miRNA profiles have been
identified for several samples from patients with bladder cancer. MicroRNAs are
noncoding RNA molecules of approximately 23 nucleotides that play important roles
in multiple steps during the progression of bladder cancer. Here, we review the
expression profiles of miRNAs and their biological functions, regulation, and
clinical implications in bladder cancer. Either downregulation or upregulation of
miRNAs occurs in bladder cancer through epigenetic changes or defects of the
biogenesis apparatus. Deregulation of miRNAs is involved in cell cycle arrest,
apoptosis, proliferation, metastasis, drug resistance, and other functions in
bladder cancer. A number of miRNAs, have been associated with tumor type, stage,
or patient survival, and miRNAs might be developed as diagnostic or prognostic
markers. A better understanding of the roles of miRNAs in bladder cancer will
shed light on the molecular mechanisms of bladder cancer.
PMID- 28491851
TI - Pemetrexed-induced acute kidney failure following irreversible renal damage: two
case reports and literature review.
AB - BACKGROUND: Pemetrexed (PEM) is a new-generation multitargeted antifolate agent
with a demonstrated broad-spectrum activity in several types of human cancers,
including non-small cell lung cancer (NSCLC) and mesothelioma. Major side effects
include dose-limiting hematologic toxicities. PEM nephrotoxicity is well known;
however, its frequency is considered to be low. CASE PRESENTATION: Here we report
two cases of acute kidney injury (AKI) related to PEM administration (500 mg/m2)
in patients with NSCLC. The first patient required hemodialysis treatment and was
submitted to renal biopsy which showed acute tubular damage and interstitial
edema without acute tubular necrosis. No other potential nephrotoxic agents were
identified. The second patient developed AKI, not proven by biopsy and did not
require renal replacement therapy. Both patients, on regular supplementation with
folic acid and vitamin B12, concomitantly developed myelosuppression and even
several months after PEM withdrawal, showed only a modest improvement of renal
function. CONCLUSIONS: PEM is an antifolate antineoplastic agent with a broad
spectrum activity in locally advanced or metastatic NSCLC. It has been shown that
PEM allows longer survival. The risk of acute or chronic kidney disease may be
one of the prices to be paid for this success.
PMID- 28491852
TI - A case of recurrent hematuria in primary prostatic low grade mucosa associated
lymphoid tissue.
AB - BACKGROUND: Primary mucosa-associated lymphoid tissue (MALT) lymphoma is a rare
malignancy. We found only 8 cases of MALT lymphoma in literature. CASE
PRESENTATION: We report here another case of primary prostatic MALT lymphoma
which is presented by hematuria and diagnosed primarily as BPH.
Immunohistochemistry studies demonstrate the diagnosis and MALT lymphoma. Six
months after starting the treatment the patient was alive and well. CONCLUSIONS:
Prostatic MALTomas are mainly presented with urinary obstruction or hematuria and
have an indolent growth with a good prognosis.
PMID- 28491853
TI - Infection associated acute interstitial nephritis; a case report.
AB - BACKGROUND: Acute interstitial nephritis (AIN) is a clinico-pathological syndrome
associated with a variety of infections, drugs, and sometimes with unknown
causes. It is a common cause of acute kidney injury (AKI) and subsequent renal
impairment, which often times is under-diagnosed. Infection-associated AIN occurs
as a consequence of many systemic bacterial, viral, and parasitic infec-tions;
however, its incidence has decreased significantly after the advent of
antimicrobials. Infection-associated AIN presents with both oliguric or non
oliguric renal insufficiency, without the classical clinical triad of AIN (fever,
rash, and arthralgia). In this scenario the renal function is usually reversible
after the infection is treated. In most cases, patients with acute renal failure
present with extra-renal manifestations typically detected in underlying
infections. Renal biopsy serves as the most definitive test for both the
diagnosis and prognosis of AIN. CASE PRESENTATION: In this paper, we will address
one such case of biopsy-proven AIN. In this case, the patient presented with
severe AKI induced by anaerobic streptococcus, leading to a periodontal abscess,
which was successfully treated with corticosteroids and requiring renal
replacement therapy (RRT). CONCLUSIONS: AIN should be considered in the
differential for unexplained AKI. Initial management should include conservative
therapy by withdrawing any suspected causative agent. Renal biopsy is needed for
confirmation in cases where kidney function fails to improve within 5-7 days on
conservative therapy. Risk of immunosuppression is very important to consider
when giving steroids in patients with infection induced AIN, and steroids may
have to be delayed until the active infection is completely controlled.
PMID- 28491854
TI - MPO-ANCA-associated necrotizing glomerulonephritis in rheumatoid arthritis; a
case report and review of literature.
AB - BACKGROUND: Renal involvement in rheumatoid arthritis (RA) is common and has a
negative impact on patient survival. Only few cases have been reported of
necrotizing glomerulonephritis (GN) associated with myeloperoxidase anti
neutrophil cytoplasmic antibody (MPO-ANCA) in patients with RA. CASE
PRESENTATION: We report a patient with RA who developed a necrotizing GN
associated with ANCA-MPO, treated with rituximab (RTX). A 55-year-old man with a
27-year history of RA under secukinumab was referred to our nephrology clinic
with worsening renal function associated with microhematuria and proteinuria. Our
laboratory evaluation showed hypocomplementemia and positive titers for MPO-ANCA
(615 U/mL). A renal biopsy demonstrated pauci-immune necrotizing GN. The patient
was treated with 3 consecutive pulses of methylprednisolone followed by oral
prednisolone (1 mg/Kg) and rituximab (1000 mg, repeated 14 days later). After a
10-month follow-up, the arthritis remains well-controlled, renal function
stabilized, proteinuria improved and MPO-ANCA titer normalized (6.3 U/mL).
CONCLUSIONS: Necrotizing GN is a rare but a serious condition and an early
diagnosis is essential to treatment. This is the first case of necrotizing GN
(without extra-renal manifestations of vasculitis) in a patient with active RA,
successfully treated with RTX.
PMID- 28491855
TI - Nephrolithiasis in elderly population; effect of demographic characteristics.
AB - BACKGROUND: Kidney stone (nephrolithiasis) is one of the most common diseases.
During the past several decades, its prevalence and incidence have increased
markedly in elderly population. OBJECTIVES: This study was conducted to evaluate
the risk factors for nephrolithiasis in elderly population. PATIENTS AND METHODS:
This study was based on the Amirkola Health and Ageing Project (AHAP). Elderly
people with kidney stones in every size, type and number were considered to be
the case group and other subjects without a history of kidney stones served as
control group. Demographic and anthropometric data, smoking, diabetes and
metabolic syndrome (MetS), calcium (Ca), vitamin D, parathyroid hormone (PTH),
uric acid and urine pH were compared in both groups. RESULTS: In this study, 1390
elderly people with the mean age of 69.37 +/- 7.42 years were evaluated which 202
(14.53%) cases had renal stones. The patients with nephrolithiasis were younger
(P = 0.010) and had higher uric acid and body mass index (BMI) levels (P = 0.041
and P = 0.006, respectively). Age <75 years, male gender and BMI >=30 kg/m2 had a
significant association with stone formation. The prevalence of diabetes, MetS
and smoking in the patients with nephrolithiasis was lower than the subjects
without it. CONCLUSIONS: This study suggests that male gender, obesity and age
<75 years might be independent risk factors for the development of
nephrolithiasis. Hence, low animal protein intake and weight reduction should be
included as part of the counseling of senior stone-formers.
PMID- 28491856
TI - Renal tissue pro-inflammatory gene expression is reduced by erythropoietin in
rats subjected to hemorrhagic shock.
AB - BACKGROUND: Hemorrhagic shock (HS) is a condition produced by considerable loss
of intravascular volume, which may eventually lead to organ damage and death.
OBJECTIVES: In the present study, the potential implication of the kidney tissue
tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-10
(IL-10) were evaluated in the protective effects of erythropoietin (EPO) during
HS. MATERIALS AND METHODS: Male Wistar rats were randomized into three
experimental groups; Sham, HS (hemorrhagic shock and resuscitation), and EPO
(erythropoietin). HS was induced by 50% blood volume hemorrhage over 30 minutes.
After 2 hours, resuscitation was performed within 30 minutes. In the EPO group,
EPO (300 IU/kg, i.v.) was administered 10 minutes before HS induction. Urine was
collected to determine urinary N-acetyl-beta-D-glucosaminidase (NAG) activity
level. The kidney cytokines (TNF-alpha, IL-6 and IL-10) mRNA expressions were
measured by real-time polymerase chain reaction (PCR). RESULTS: HS rats showed
significant increase in urinary NAG activity compared to the sham group. EPO
significantly attenuated the rises in urinary NAG activity compared to the HS
group. In the HS animals, renal TNF-alpha and IL-6 mRNA expressions increased
whereas no difference was observed in IL-10 mRNA expression between the HS and
sham groups. EPO was able to decrease renal TNF-alpha and IL-6 production and
increase IL-10 mRNA expression. CONCLUSIONS: In this study, we demonstrated that
EPO attenuates kidney damage in rats subjected to HS. The beneficial effects of
EPO may be at least partly mediated by modifications in the inflammatory cascade.
PMID- 28491857
TI - Administration of zinc against arsenic-induced nephrotoxicity during gestation
and lactation in rat model.
AB - BACKGROUND: Free radicals production by toxicity of arsenic (Ar) is most
important in the nephrotoxicity. There is accumulating evidence that zinc (Zn),
has anti-oxidant properties. OBJECTIVES: The aim of present study was to evaluate
protective and ameliorative effects of Zn against Ar-induced nephrotoxicity in
rat pups during gestation and lactation. MATERIALS AND METHODS: Twenty-four adult
pregnant wistar rats were randomly divided into four groups (n = 6). Group one
was given vehicle only. Group two received Zn (ZnSO4) at 20 mg/kg/d. Group three
received Ar at 5 mg/kg/d as sodium meta-arsenite. Group four received Ar + Zn at
the same dose that mentioned in groups of two and three. At the end of the study,
24 hours after the last treatment, samples were killed with overdose of sodium
pentobarbital and kidneys were harvested for measuring malondialdehyde (MDA),
glutathione (GSH) and histopathological assessment. RESULTS: The MDA level in
kidney was increased in the Ar group, which was decreased after Zn administration
in the Ar + Zn group. The GSH level in kidney was decreased in the Ar group,
which were increased after Zn administration in the Ar + Zn group. Also, the
histopathological changes which were detected in the Ar group attenuated after Zn
consumption. CONCLUSIONS: Our findings suggested that administration of Zn during
gestation and lactation could have protective and prevent effect in Ar-induced
oxidative stress in kidney tissue.
PMID- 28491858
TI - Clinical outcomes and quality of life in hemodialysis diabetic patients versus
non-diabetics.
AB - BACKGROUND: Diabetes is the leading cause of end stage renal disease (ESRD)
worldwide. OBJECTIVES: We compared the clinical outcomes in diabetic patients on
hemodialysis (HD) with non-diabetics. PATIENTS AND METHODS: Adult maintenance HD
patients (N= 532) from 9 HD facilities were enrolled to this prospective cohort
study in September 2012. Causes of death, hospitalization, and HD exit were
recorded in a median 28 months follow up period. RESULTS: Forty-one percent of
patients were diabetic. Diabetic patients compared to non-diabetics had
significantly higher age (62.2 +/- 11.2 versus 53.1 +/- 16.7 years), lower
dialysis duration (median: 23 versus 30 months), more cardiovascular
comorbidities (64% versus 28%) , higher C-reactive protein (CRP) levels (median:
3.80 versus 2.25 mg/L), lower serum albumin (3.86 +/- 0.35 versus 3.93 +/- 0.35
g/dL), lower intact parathyroid hormone (iPTH) (median: 272 versus 374 rhog/mL),
higher serum triglyceride (167 +/- 91 versus 139 +/- 67 mg/dL) and low density
lipoprotein (LDL) (82.5 +/- 24.5 versus 77.5 +/- 23.8 mg/dL), and worse short
form health survey (SF36) score (45.7 +/- 20.9 versus 52.7 +/- 20.5). Annual
admission rate was higher in diabetics (median: 0.86 versus 0.43) and diabetic
foot involved 16% of their admissions. Transplantation rate was 4 and 9 per 100
patient years in diabetics and non-diabetics, respectively. Death rate was two
folds higher in diabetics (24 versus 12 per 100 patient years). Cardiovascular
diseases ( +/- infections/other causes) comprised 80.5% of death in diabetics and
54.5% in non-diabetics. In Cox regression proportional hazard multivariate
analysis, hazard risk of death in diabetics was 1.9 times higher than non
diabetics. CONCLUSIONS: Clinical outcomes and health related quality of life
(HRQOL) are much worse in diabetic compared to non-diabetic HD patients mainly
due to more frequent of cardiovascular diseases (CVDs).
PMID- 28491859
TI - Autophagy in kidney transplants of sirolimus treated recipients.
AB - BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors are increasingly used
as immunosuppressive agents in kidney transplantation. In the experimental
setting it has been shown that mTOR inhibitors promote autophagy, but the concept
that this might also occur in transplant patients has not been addressed.
OBJECTIVES: This study was designed to investigate the association between mTOR
inhibition and autophagy in renal transplants under routine clinical conditions.
MATERIALS AND METHODS: Protocol transplant biopsies of patients receiving
sirolimus were compared to biopsies of patients treated without mTOR inhibitor.
Electron microscopy was used for quantitative stereological analysis of
autophagosomal volume fractions. Ultrastructural analysis was focused on
podocytes to avoid cell type bias. Autophagy-related gene products were profiled
by QPCR from laser assisted microdissected glomeruli and by immunohistochemistry
for semiquantitative evaluation. RESULTS: By electron microscopy, we observed a
significant > 50% increase in podocytic autophagosomal volume fractions in
patients treated with sirolimus. Evaluation of biopsy material from the same
patients using transcriptional profiling of laser capture microdissected
glomeruli revealed no differences in autophagy-related gene expressions.
Immunohistochemical evaluation of autophagic degradation product p62 was also
unaltered whereas a significant increase was observed in podocytic LC3 positivity
in biopsies of sirolimus treated patients. CONCLUSIONS: These results indicate an
association of sirolimus treatment and autophagosome formation in transplant
patients. However, they might reflect autophagosomal buildup rather than
increased autophagic flux. Further research is needed to investigate the
potential functional consequences in short- and long-term outcome of patients
treated with mTOR inhibitors.
PMID- 28491860
TI - Differences in the frequency of macrophage and T cell markers between focal and
crescentic classes of anti-neutrophil cytoplasmic antibody (ANCA)-associated
glomerulonephritis.
AB - BACKGROUND: Anti-neutrophil cytoplasmic antibody (ANCA)-associated
glomerulonephritis (AAGN) can be classified into; focal, crescentic, mixed and
sclerotic classes. Macrophages and T lymphocytes are key players in mediating
renal injury. The frequency of macrophage and T lymphocytes in different
histological classes is unclear. OBJECTIVES: We examined the frequency of
macrophage and T lymphocyte markers in AAGN and assessed their correlation with
renal function at presentation. PATIENTS AND METHODS: Renal biopsies from 38
patients were included in immunohistochemistry analysis of macrophages (CD68,
sialoadhesin [Sn] and mannose receptor [MR]) and T cells (CD4 and CD8) markers.
The frequency of these markers in glomerular, periglomerular and interstitial
compartments were measured in a blinded fashion. Biopsies were allocated a
histological class of focal, crescentic, mixed or sclerotic. Scores were then
matched to histological class and assessed for correlation with renal function.
RESULTS: The biopsies were crescentic 19 (50%), focal 10 (26.3%), mixed 6 (15.7%)
and sclerotic 3 (8%). Interstitial CD68+ macrophages and CD8+ T lymphocytes
showed best correlation with renal function at the time of presentation. CD68+
macrophages were significantly increased in crescentic compared to focal AAGN.
MR+ macrophages, CD4 and CD8 T cells were also elevated in the interstitium of
crescentic compared to focal group. CONCLUSIONS: In this study interstitial CD68
and CD8 showed the highest association with the renal function at presentation.
Differences in the cellular infiltrate between focal and crescentic AAGN were
related to CD68+ macrophages and to interstitial MR+ macrophages and T
lymphocytes. Further studies are needed to assess these differences across all
four histological categories.
PMID- 28491861
TI - Enteric-coated and highly standardized cranberry extract reduces antibiotic and
nonsteroidal anti-inflammatory drug use for urinary tract infections during
radiotherapy for prostate carcinoma.
AB - INTRODUCTION: Worldwide, bacterial resistance to antibiotic therapy is a major
concern for the medical community. Antibiotic resistance mainly affects Gram
negative bacteria that are an important cause of lower urinary tract infections
(LUTIs). Pelvic irradiation for prostate cancer is a risk factor for LUTIs.
Cranberry extract is reported to reduce the incidence of LUTIs. The prophylactic
role of an enteric-coated, highly standardized cranberry extract (VO370(r)) in
reducing LUTI episodes, urinary discomfort, and nonsteroidal anti-inflammatory
drug (NSAID) and antibiotic use during radiotherapy for prostate carcinoma was
evaluated. METHODS: A total of 924 patients with prostate carcinoma treated by
radiotherapy to the prostatic and pelvic areas were randomized to receive (n=489)
or not (n=435) the enteric-coated, highly standardized cranberry extract for 6-7
weeks concurrently with irradiation. Outcomes were analyzed by using Mann-Whitney
U test and Pearson's chi2 test. Primary endpoint was the number of patients with
LUTI; secondary endpoints were incidence of recurrence, days of treatment with
antibiotics and number of subjects treated with NSAIDs, and incidence of dysuria.
RESULTS: The treatment was very well tolerated, and there were no serious side
effects. All enrolled patients completed the study. Urinary infections were
detected in 53 of the 489 patients (10.8%) treated with enteric-coated, highly
standardized cranberry extract, while 107 of the 435 patients (24.6%) in the
control group developed LUTIs (p=0.0001). A clear and significant reduction in
urinary discomfort of ~50% was seen in treated subjects. The treatment also
resulted in ~50% reduction in the use of anti-inflammatory drugs and antibiotics.
CONCLUSION: The enteric-coated, highly standardized cranberry extract could be
used as a prophylactic to reduce the incidence of LUTIs and decrease antibiotic
therapy in patients receiving pelvic irradiation for prostate cancer.
PMID- 28491862
TI - Comparison of Fecal Calprotectin Methods for Predicting Relapse of Pediatric
Inflammatory Bowel Disease.
AB - Background. Pediatric inflammatory bowel disease (IBD) is on the rise worldwide.
Endoscopies are necessary for IBD assessment but are invasive, expensive, and
inconvenient. Recently, fecal calprotectin (FCal) was proposed as a noninvasive
and specific marker of gut inflammation. We evaluated the analytical performance
of three FCal assays and their clinical performance in predicting relapse in
pediatric IBD. Methods. This study used 40 pediatric IBD and 40 random non-IBD
patients' fecal samples. Two automated ELISAs (Buhlmann and PhiCal(r)
Calprotectin-EIA) and an EliA (Phadia 250 EliA-Calprotectin) were used to
evaluate the analytical performance. The clinical performance was assessed by
PhiCal Calprotectin-EIA, EliA-Calprotectin, and Buhlmann immunochromatographic
point-of-care test (POCT). Results. All assays displayed acceptable analytical
performance below and above the medical decision cut-off [imprecision (CV < 10%
intra-assay; <15% interassay); linearity (overall mean % deviation < 16.5%)]. The
agreement with PhiCal Calprotectin-EIA was 100% and 78.6% for Buhlmann (95% CI,
87.5-100; Kappa: 1) and EliA-Calprotectin (95% CI, 60.5-89.8; Kappa: 0.32),
respectively, and 63.6% between Buhlmann and EliA-Calprotectin (95% CI, 46.6
77.8; Kappa: 0.16). All assays evaluated had similar clinical performance [AUC:
0.84 (EliA-Calprotectin); 0.83 (POCT and PhiCal Calprotectin-EIA)]. Conclusion.
FCal levels determined using the same method and assay together with clinical
history would be a noninvasive and useful tool in monitoring pediatric IBD.
PMID- 28491863
TI - Reproducing Patient-Specific Hemodynamics in the Blalock-Taussig Circulation
Using a Flexible Multi-Domain Simulation Framework: Applications for Optimal
Shunt Design.
AB - For babies born with hypoplastic left heart syndrome, several open-heart
surgeries are required. During Stage I, a Norwood procedure is performed to
construct an appropriate circulation to both the systemic and the pulmonary
arteries. The pulmonary arteries receive flow from the systemic circulation,
often using a Blalock-Taussig (BT) shunt between the innominate artery and the
right pulmonary artery. This procedure causes significantly disturbed flow in the
pulmonary arteries. In this study, we use computational hemodynamic simulations
to demonstrate its capacity for examining the properties of the flow through and
near the BT shunt. Initially, we construct a computational model which produces
blood flow and pressure measurements matching the clinical magnetic resonance
imaging (MRI) and catheterization data. Achieving this required us to determine
the level of BT shunt occlusion; because the occlusion is below the MRI
resolution, this information is difficult to recover without the aid of
computational simulations. We determined that the shunt had undergone an
effective diameter reduction of 22% since the time of surgery. Using the
resulting geometric model, we show that we can computationally reproduce the
clinical data. We, then, replace the BT shunt with a hypothetical alternative
shunt design with a flare at the distal end. Investigation of the impact of the
shunt design reveals that the flare can increase pulmonary pressure by as much as
7% and flow by as much as 9% in the main pulmonary branches, which may be
beneficial to the pulmonary circulation.
PMID- 28491864
TI - Can Getting Enough Vitamin D during Pregnancy Reduce the Risk of Getting Asthma
in Childhood?
AB - The worldwide increase in asthma prevalence during the last decades and the re
emergence of vitamin D deficiency in many populations hinted toward an underlying
association between these two conditions. Since asthma is presented with high
incidence in childhood and neonatal vitamin D stores depend on maternal vitamin
levels, a possible programming effect of maternal vitamin D status during
gestation was suggested. Observational and longitudinal studies on this subject
led to inconclusive results with glimmer of positivity. In the randomized
controlled clinical trials (RCTs) that followed, increased doses of vitamin D
were tested in pregnant women being at high risk of having an asthmatic child.
Although, the results of RCTs showed a potential association with asthma-related
phenotypes rather than asthma per se, the low toxicity of vitamin D supplements
make it tempting to speculate that pregnant women at a high risk of obtaining a
child with asthma may be benefited, especially if they are vitamin D deficient.
PMID- 28491865
TI - The Role of the Central Nervous System Microenvironment in Pediatric Acute
Lymphoblastic Leukemia.
AB - Acute lymphoblastic leukemia (ALL) is the most common cancer in children. While
survival rates for ALL have improved, central nervous system (CNS) relapse
remains a significant cause of treatment failure and treatment-related morbidity.
Accordingly, there is a need to identify more efficacious and less toxic CNS
directed leukemia therapies. Extensive research has demonstrated a critical role
of the bone marrow (BM) microenvironment in leukemia development, maintenance,
and chemoresistance. Moreover, therapies to disrupt mechanisms of BM
microenvironment-mediated leukemia survival and chemoresistance represent new,
promising approaches to cancer therapy. However, in direct contrast to the
extensive knowledge of the BM microenvironment, the unique attributes of the CNS
microenvironment that serve to make it a leukemia reservoir are not yet
elucidated. Recent work has begun to define both the mechanisms by which leukemia
cells migrate into the CNS and how components of the CNS influence leukemia
biology to enhance survival, chemoresistance, and ultimately relapse. In addition
to providing new insight into CNS relapse and leukemia biology, this area of
investigation will potentially identify targetable mechanisms of leukemia
chemoresistance and self-renewal unique to the CNS environment that will enhance
both the durability and quality of the cure for ALL patients.
PMID- 28491866
TI - Pulmonary Extracellular Vesicles as Mediators of Local and Systemic Inflammation.
AB - Cells of the airways are constantly exposed to environmental hazards including
cigarette smoke, irritants, pathogens, and mechanical insults. Maintaining
barrier integrity is vital, and mounting responses to threats depends on
intercellular communication. Extracellular vesicles (EVs), including exosomes and
microvesicles, are major signal mediators between cells, shuttling cargo in
health and disease. Depending on the state of the originating cells, EVs are
capable of inducing proinflammatory effects including antigen presentation,
cellular migration, apoptosis induction, and inflammatory cytokine release. Cells
of the airways release EVs, which can be found in bronchoalveolar lavage fluid.
EVs of the airways can support inflammation in the lung, but may also exit into
the circulation and carry a cocktail of pro-inflammatory molecules to recipient
cells in distant organs. In this review, we discuss the possibility that EVs
originating from the airways contribute to dissemination of inflammation in both
lung disorders and systemic inflammatory conditions.
PMID- 28491868
TI - FluoroType MTB system for the detection of pulmonary tuberculosis.
AB - FluoroType MTB is a sensitive test for TB but specificity is low compared with
fully integrated molecular systems http://ow.ly/WhEO30b1luY.
PMID- 28491869
TI - Prevalence and Associated Factors of Suicidal Ideation and Attempt among People
Living with HIV/AIDS at Zewditu Memorial Hospital, Addis Ababa, Ethiopia: A Cross
Sectional Study.
AB - Background. Human Immune Deficiency Virus (HIV/AIDS) continues to be an
underrecognized risk for suicidal ideation, suicidal attempt, and completion of
suicide. Suicidal ideation and attempt in HIV/AIDS is not only a predictor of
future attempted suicide and completed suicide. Methods. An institution based
cross-sectional study was conducted among HIV-positive patients attending HIV
care at Zewditu Memorial Hospital. Systematic random sampling technique was used
to recruit 423 participants from April to May 2014. Composite International
Diagnostic Interview was used to collect data. Multivariable logistic regression
was computed to assess factors associated with suicidal ideation and attempt.
Result. Suicidal ideation and suicidal attempt were found to be 22.5% and 13.9%,
respectively. WHO clinical stage of HIV, not being on HAART, depression, family
history of suicidal attempt, and perceived stigma were associated with suicidal
ideation. WHO clinical stage, being female, not being on HAART, use of substance,
and depression were associated with suicidal attempt. Conclusion. Early diagnosis
and treatment of opportunistic infections, depression, and early initiation of
ART need to be encouraged in HIV-positive adults. Furthermore, counseling on
substance use and its consequences and early identification of HIV-positive
people with family history of suicidal ideation have to be considered.
PMID- 28491867
TI - Metabolic Reprogramming in Glioma.
AB - Many cancers have long been thought to primarily metabolize glucose for energy
production-a phenomenon known as the Warburg Effect, after the classic studies of
Otto Warburg in the early twentieth century. Yet cancer cells also utilize other
substrates, such as amino acids and fatty acids, to produce raw materials for
cellular maintenance and energetic currency to accomplish cellular tasks. The
contribution of these substrates is increasingly appreciated in the context of
glioma, the most common form of malignant brain tumor. Multiple catabolic
pathways are used for energy production within glioma cells, and are linked in
many ways to anabolic pathways supporting cellular function. For example:
glycolysis both supports energy production and provides carbon skeletons for the
synthesis of nucleic acids; meanwhile fatty acids are used both as energetic
substrates and as raw materials for lipid membranes. Furthermore, bio-energetic
pathways are connected to pro-oncogenic signaling within glioma cells. For
example: AMPK signaling links catabolism with cell cycle progression; mTOR
signaling contributes to metabolic flexibility and cancer cell survival; the
electron transport chain produces ATP and reactive oxygen species (ROS) which act
as signaling molecules; Hypoxia Inducible Factors (HIFs) mediate interactions
with cells and vasculature within the tumor environment. Mutations in the tumor
suppressor p53, and the tricarboxylic acid cycle enzymes Isocitrate Dehydrogenase
1 and 2 have been implicated in oncogenic signaling as well as establishing
metabolic phenotypes in genetically-defined subsets of malignant glioma. These
pathways critically contribute to tumor biology. The aim of this review is two
fold. Firstly, we present the current state of knowledge regarding the metabolic
strategies employed by malignant glioma cells, including aerobic glycolysis; the
pentose phosphate pathway; one-carbon metabolism; the tricarboxylic acid cycle,
which is central to amino acid metabolism; oxidative phosphorylation; and fatty
acid metabolism, which significantly contributes to energy production in glioma
cells. Secondly, we highlight processes (including the Randle Effect, AMPK
signaling, mTOR activation, etc.) which are understood to link bio-energetic
pathways with oncogenic signals, thereby allowing the glioma cell to achieve a
pro-malignant state.
PMID- 28491870
TI - Noninvasive Retinal Markers in Diabetic Retinopathy: Advancing from Bench towards
Bedside.
AB - The retinal vascular system is the only part of the human body available for
direct, in vivo inspection. Noninvasive retinal markers are important to identity
patients in risk of sight-threatening diabetic retinopathy. Studies have
correlated structural features like retinal vascular caliber and fractals with
micro- and macrovascular dysfunction in diabetes. Likewise, the retinal
metabolism can be evaluated by retinal oximetry, and higher retinal venular
oxygen saturation has been demonstrated in patients with diabetic retinopathy. So
far, most studies have been cross-sectional, but these can only disclose
associations and are not able to separate cause from effect or to establish the
predictive value of retinal vascular dysfunction with respect to long-term
complications. Likewise, retinal markers have not been investigated as markers of
treatment outcome in patients with proliferative diabetic retinopathy and
diabetic macular edema. The Department of Ophthalmology at Odense University
Hospital, Denmark, has a strong tradition of studying the retinal
microvasculature in diabetic retinopathy. In the present paper, we demonstrate
the importance of the retinal vasculature not only as predictors of long-term
microvasculopathy but also as markers of treatment outcome in sight-threatening
diabetic retinopathy in well-established population-based cohorts of patients
with diabetes.
PMID- 28491871
TI - The Imbalance of B-Lymphocyte Subsets in Subjects with Different Glucose
Tolerance: Relationship with Metabolic Parameter and Disease Status.
AB - B lymphocytes are involved in inflammation and are related to insulin resistance
in obesity and type 2 diabetes (T2D). This study investigated the phenotype and
frequency of B-lymphocyte subsets in subjects recently diagnosed with T2D (n =
60), impaired glucose regulation (IGR, n = 73), and normal glucose tolerance
(NGT, n = 169) by flow cytometry. T2D subjects had an increased percentage of
CD19+CD23+ (B-2) cells and a decreased percentage of CD19+CD23- (B-1) cells
attributing to CD19+CD23-CD5- (B-1b) cells, but not CD19+CD23-CD5+ (B-1a) cells,
compared to NGT and IGR subjects. The proportion of CD19+CD5+CD1dhi (B10) cells
did not differ between the IGR or T2D group and NGT controls. Of note, HbA1c and
triglyceride showed a positive correlation with B-2 cells but an inverse
correlation with B-1 and B-1b cells, which were independently associated with the
presence of T2D by logistic regression models. In summary, this study shows an
unbalanced proinflammatory phenotype of B-cell subsets correlated with glycemia
and lipidemia in patients with T2D. Our data provide new insight into chronic
activation of the immune system and subclinical inflammation in T2D. Further
prospective studies are warranted to confirm our observations.
PMID- 28491872
TI - Incidence and Contributing Factors of Persistent Hyperglycemia at 6-12 Weeks
Postpartum in Iranian Women with Gestational Diabetes: Results from LAGA Cohort
Study.
AB - Background. A history of gestational diabetes is an important predictor of many
metabolic disturbances later in life. Method. Life after gestational diabetes
Ahvaz Study (LAGAs) is an ongoing population-based cohort study. Up to February
2016, 176 women with gestational diabetes underwent a 75 g oral glucose tolerance
test (OGTT) at 6-12 weeks postpartum in Ahvaz (southwestern of Iran). Gestational
diabetes was diagnosed according to the International Association of Diabetes and
Pregnancy Study Groups (IADPSG) criteria and the American Diabetes Association
(ADA) criteria applied for diagnosis of postpartum prediabetes and diabetes.
Univariate and multivariate regression analysis were done. Results. Overall
incidence of early postpartum glucose intolerance was 22.2% (95% CI, 16.3-29.0),
17.6% prediabetes (95% CI, 12.3-24.1) and 4.5% diabetes (95% CI, 2.0-8.8%).
Independent risk factors for glucose intolerance were FPG >= 100 at the time of
OGTT (OR 3.86; 95% CI; 1.60-9.32), earlier diagnosis of GDM (OR 0.92; 95% CI;
0.88-0.97), systolic blood pressure (OR 1.02; 95% CI; 1.002-1.04), and insulin or
metformin therapy (OR 3.14; 95% CI; 1.20-8.21). Conclusion. Results determined a
relatively high rate of glucose intolerance at 6-12 weeks after GDM pregnancy.
Early postpartum screening of type 2 diabetes is needed particularly in women at
high risk of type 2 diabetes.
PMID- 28491874
TI - Innate-Adaptive Immune Crosstalk 2016.
PMID- 28491873
TI - B-CD8+ T Cell Interactions in the Anti-Idiotypic Response against a Self
Antibody.
AB - P3 is a murine, germline, IgM mAb that recognizes N-glycolylated gangliosides and
other self-antigens. This antibody is able to induce an anti-idiotypic IgG
response and B-T idiotypic cascade, even in the absence of any adjuvant or
carrier protein. P3 mAb immunization induces the expression of activation markers
in a significant percentage of B-1a cells in vivo. Interestingly, transfer of
both B-1a and B-2 to BALB/Xid mice was required to recover anti-P3 IgG response
in this model. In fact, P3 mAb activated B-2 cells, in vitro, inducing secretion
of IFN-gamma and IL-4, although this activation was not detected ex vivo.
Interestingly, naive CD8+ T cells increased the expression of activation markers
and IFN-gamma secretion in the presence of B-1a cells isolated from P3 mAb
immunized mice, even without in vitro restimulation. In contrast, B-2 cells were
able to stimulate CD8+ T cells only if P3 was added in vitro. Using
bioinformatics, a MHC class I-binding peptide from P3 VH region was identified.
P3 mAb was able to induce a specific CTL response in vivo against cells
presenting this peptide. Both humoral and CTL anti-idiotypic responses could be
mechanisms to protect against the self-reactive antibody, contributing to keeping
the tolerance to self-antigens.
PMID- 28491875
TI - Understanding the Role of Chemokines and Cytokines in Experimental Models of
Herpes Simplex Keratitis.
AB - Herpes simplex keratitis is a disease of the cornea caused by HSV-1. It is a
leading cause of corneal blindness in the world. Underlying molecular mechanism
is still unknown, but experimental models have helped give a better understanding
of the underlying molecular pathology. Cytokines and chemokines are small
proteins released by cells that play an important proinflammatory or anti
inflammatory role in modulating the disease process. Cytokines such as IL-17, IL
6, IL-1alpha, and IFN-gamma and chemokines such as MIP-2, MCP-1, MIP-1alpha, and
MIP-1beta have proinflammatory role in the destruction caused by HSV including
neutrophil infiltration and corneal inflammation, and other chemokines and
cytokines such as IL-10 and CCL3 can have a protective role. Most of the damage
results from neutrophil infiltration and neovascularization. While many more
studies are needed to better understand the role of these molecules in both
experimental models and human corneas, current studies indicate that these
molecules hold potential to be targets of future therapy.
PMID- 28491876
TI - New Biomarkers in Autoimmune Disease.
PMID- 28491877
TI - Nodular Regenerative Hyperplasia: A Case of Rare Prognosis.
AB - Introduction: Nodular regenerative hyperplasia (NRH) is a known etiology of
noncirrhotic portal hypertension. Cases of biopsy-proven NRH in human
immunodeficiency virus (HIV)-positive patients have been described. While these
patients often have normal synthetic liver function, several reports described
disease progression to liver failure. Case: We here present a 26-year-old woman
with history of congenital HIV on antiretroviral therapy complicated by
Pneumocystis carinii pneumonia at age 14. CD4 counts have been >300 with
undetectable viral load. She was referred to our Hepatology service for
evaluation of splenomegaly, elevated liver tests, and thrombocytopenia. On
initial presentation, she reported easy bruising and gingival bleeding, and
abdominal imaging showed evidence of portal hypertension without associated
cirrhosis. Upper endoscopy was significant for large esophageal varices without
bleeding stigmata. Liver biopsy showed minimal fibrosis around the portal areas
without significant inflammation. The lobules showed focal zones of thin
hepatocyte plates on reticulin stain with adjacent areas showing mild
regenerative changes. The diagnosis of NRH was made and patient was placed on
propranolol for variceal bleeding prophylaxis. Two years later, the patient
presented with bleeding gastric varices warranting transjugular intrahepatic
portosystemic shunt. Postprocedure course was complicated by mild encephalopathy.
Subsequent magnetic resonance imaging showed a 1.7 * 1.3 cm lesion suggestive of
hepatocellular carcinoma (HCC). The patient was deemed to be a candidate for
liver transplantation, and she is now delisted due to ongoing pregnancy.
Conclusion: This report describes the first case of HCC in an HIV patient with
NRH. The possible association of NRH with HCC warrants further investigation.
PMID- 28491878
TI - A Case of Severe Neutropenia From Short-Term Exposure to Moxifloxacin.
AB - Moxifloxacin is commonly prescribed in the inpatient and outpatient management of
community-acquired pneumonia and other common infections. We report a case of a
76-year-old man who developed severe neutropenia after several days of treatment
for community-acquired pneumonia. The patient had a history of alcohol abuse;
however, there were no other offending medications prescribed, and a thorough
laboratory workup for other possible causes of neutropenia was negative. The
patient's neutrophils and white blood count responded quickly to cessation of
fluoroquinolones. This case highlights the importance of identifying patients
that might be at high risk for neutropenia that may need closer monitoring on
this commonly prescribed medication.
PMID- 28491879
TI - Listeria Endocarditis: A Diagnostic Challenge.
AB - A 74-year-old hemodialysis patient with a history of an atrial septum defect
closure, coronary bypass surgery, and a St. Jude aortic prosthetic valve was
diagnosed with pneumonia and volume overload. Blood cultures were positive for
Listeria monocytogenes, and amoxicillin was given for 2 weeks. Immediately after
discontinuation of amoxicillin, fever relapsed. Transthoracic and transesophageal
echocardiography showed no sign of endocarditis. Given the fever relapse and 3
positive minor Duke criteria, an 18F-FDG PET-CT scan (18F-fluorodeoxyglucose
positron emission tomography-computed tomography) scan was performed. This scan
showed activity at the aortic root, proximal ascending aorta, and inferior wall
of the heart, making Listeria monocytogenes endocarditis a likely explanation.
Amoxicillin was given for 6 weeks with good clinical result. Diagnosing a life
threatening Listeria monocytogenes endocarditis can be challenging and an 18F-FDG
PET-CT scan can be helpful.
PMID- 28491880
TI - Iron Refractory Iron Deficiency Anemia in Dizygotic Twins Due to a Novel TMPRSS6
Gene Mutation in Addition to Polymorphisms Associated With High Susceptibility to
Develop Ferropenic Anemia.
AB - Iron refractory iron deficiency anemia (IRIDA) is an autosomal recessive
ferropenic anemia. Its hypochromic microcytic pattern is associated with low
transferrin saturation, normal-high ferritin, and inappropriately high hepcidin
level. This entity is caused by mutants of the TMPRSS6 gene that encodes the
protein matriptase II, which influences hepcidin expression, an iron metabolism
counterregulatory protein. We report two 29-year-old dizygotic female twins with
ferropenic, hypochromic microcytic anemia with 20 years of evolution, refractory
to oral iron therapy. After exclusion of gastrointestinal etiologies, IRIDA
diagnosis was suspected and a novel mutation in the TMPRSS6 gene was identified.
It was found in intron 11 (c.1396+4 A>T) and seems to affect the gene expression.
In addition, 3 polymorphisms already associated with a higher risk of developing
iron deficiency anemia were also found (D521D, V736A, and Y739Y). Our case
reports an undescribed mutation causing IRIDA and supports the hypothesis that
this clinical syndrome may be more common than previously thought and its
genetics more heterogeneous than initially described.
PMID- 28491881
TI - Corrigendum.
AB - [This corrects the article DOI: 10.1177/2324709616689106.].
PMID- 28491882
TI - Portal Vein Thrombosis in the Setting of Newly Diagnosed Cushing's Syndrome.
AB - The hallmark manifestations of Cushing's syndrome (CS) are well known, but
hypercoagulability is perhaps least recognized. Patients with CS are at increased
risk of both spontaneous and postoperative thromboembolism, with the significant
majority of events occurring in the lower extremity and pulmonary venous
circulations. We present a case of portal vein thrombosis (PVT) occurring in the
setting of newly diagnosed CS due to a left adrenal adenoma. Factor VIII activity
was approximately 2.5-fold elevated, a known mechanism by which hypercortisolemia
predisposes to venous thrombosis. Acute abdominal pain and fever responded well
to unfractionated heparin and parenteral antibiotics, and CS was eventually cured
by left adrenalectomy. No thromboembolic events have occurred since surgery. PVT
is uncommon and usually occurs as a complication of primary or secondary
hepatobiliary malignancies and cirrhosis. To the best of our knowledge, this is
just the second reported case of PVT due to CS and the first published in the
English language literature.
PMID- 28491883
TI - Haemophilus parainfluenzae Endocarditis Associated With Maxillary Sinusitis and
Complicated by Cerebral Emboli in a Young Man.
AB - HACEK endocarditis is often difficult to diagnose given the slow-growing
characteristics of the organisms involved. Haemophilus parainfluenzae, one of the
HACEK organisms, is an uncommon cause of endocarditis. We describe a case of a
previously healthy young man with H parainfluenzae endocarditis that was
associated with maxillary sinusitis and severe systemic complications, including
septic cerebral emboli and mitral valve perforation. Previously reported cases
have also described a predilection for younger people, cardiac valve pathology,
and a high prevalence of stroke.
PMID- 28491884
TI - Association of Autoimmune Hepatitis and Celiac Disease: Role of Gluten-Free Diet
in Reversing Liver Dysfunction.
AB - Autoimmune hepatitis (AIH) is a chronic inflammation of liver with unclear
etiology. It is frequently associated other autoimmune diseases, and its
association with celiac disease (CD) is well established. In this article, we
describe the case of a 50-year-old male with long-standing AIH taking
azathioprine for 10 years, evaluated for flares in transaminases. Despite adding
high-dose corticosteroids, his transaminases and bilirubin remained high.
Serology for CD was ordered, which revealed elevated tissue transglutaminase
antibody IgG and endomysial IgA, which was further confirmed by endoscopic
biopsy. Strict gluten-free diet was advised and now for over 2 years he is in
remission with azathioprine and budesonide. This emphasizes the role of gluten
free diet in reversing liver dysfunction in patients with AIH, and clinicians
should consider screening for CD in patients with AIH with persistent elevation
of liver enzymes despite immunosuppressant treatment.
PMID- 28491886
TI - The Effect of the Number of Carries Among College Running Backs on Future Injury
Risk and Performance in the National Football League.
AB - BACKGROUND: There has been speculation that running backs with an excessive
number of carries in college are less likely to be successful in the National
Football League (NFL). PURPOSE: To determine whether there is a correlation
between number of carries by college running backs and future performance and
injury risk in the NFL. STUDY DESIGN: Cohort study; Level of evidence, 3.
METHODS: Using the ESPN archives of National Collegiate Athletic Association and
NFL running backs, the following inclusion criteria were used: running backs who
played their last college season from 1999 through 2012 and who were drafted in
the first 4 rounds of the NFL draft following their college career. Players were
grouped by number of carries during their final college season (group A, 100-200
carries; group B, 250+ carries). Performance and injury risk were compared
between groups during the first 3 eligible seasons in the NFL. Groups were
compared based on total number of carries, mean yards per carry, number of games
missed due to injury, and the specific injuries resulting in missed playing time.
RESULTS: During the seasons studied, a total of 103 running backs were included
(group A, n = 42; group B, n = 61). There was a trend toward a significantly
greater mean total number of carries through 3 NFL seasons in group B (group A, n
= 276 carries; group B, n = 376 carries; P = .058). Mean yards per carry did not
differ between groups (group A, n = 3.9 yards/carry; group B, n = 4.0
yards/carry; P = .67). Groups A and B missed a mean 5.8 and 5.7 games,
respectively, due to injury during their first 3 NFL seasons (P = .98). A
significantly greater proportion of players in group A suffered a concussion
compared with group B (P = .014). CONCLUSION: There is no correlation between the
number of carries by college running backs and future injury risk or performance
during their early NFL career.
PMID- 28491885
TI - Effects of Sex and Event Type on Head Impact in Collegiate Soccer.
AB - BACKGROUND: The effects of head impact in sports are of growing interest for
clinicians, scientists, and athletes. Soccer is the most popular sport worldwide,
but the burden of head impact in collegiate soccer is still unknown. PURPOSE: To
quantify head impact associated with practicing and playing collegiate soccer
using wearable accelerometers. STUDY DESIGN: Descriptive epidemiological study.
METHODS: Mastoid patch accelerometers were used to quantify head impact in
soccer, examining differences in head impact as a function of sex and event type
(practice vs game). Seven female and 14 male collegiate soccer players wore
mastoid patch accelerometers that measured head impacts during team events. Data
were summarized for each athletic exposure, and statistical analyses evaluated
the mean number of impacts, mean peak linear acceleration, mean peak rotational
acceleration, and cumulative linear and rotational acceleration, each grouped by
sex and event type. RESULTS: There were no differences in the frequency or
severity of head impacts between men's and women's soccer practices. For men's
soccer, games resulted in 285% more head impacts than practices, but there were
no event-type differences in mean impact severity. Men's soccer games resulted in
more head impacts than practices across nearly all measured impact severities,
which also resulted in men's soccer games producing a greater cumulative impact
burden. CONCLUSION: Similar to other sports, men's soccer games have a greater
impact burden when compared with practices, and this effect is driven by the
quantity rather than severity of head impacts. In contrast, there were no
differences in the quantity or severity of head impacts in men's and women's
soccer practices. These data could prompt discussions of practical concern to
collegiate soccer, such as understanding sex differences in head impact and
whether games disproportionately contribute to an athlete's head impact burden.
PMID- 28491887
TI - Risk Factors for Surgical Site Infection After Cholecystectomy.
AB - BACKGROUND: There are limited data on risk factors for surgical site infection
(SSI) after open or laparoscopic cholecystectomy. METHODS: A retrospective cohort
of commercially insured persons aged 18-64 years was assembled using
International Classification of Diseases, 9th Revision, Clinical Modification
(ICD-9-CM) procedure or Current Procedural Terminology, 4th edition codes for
cholecystectomy from December 31, 2004 to December 31, 2010. Complex procedures
and patients (eg, cancer, end-stage renal disease) and procedures with pre
existing infection were excluded. Surgical site infections within 90 days after
cholecystectomy were identified by ICD-9-CM diagnosis codes. A Cox proportional
hazards model was used to identify independent risk factors for SSI. RESULTS:
Surgical site infections were identified after 472 of 66566 (0.71%)
cholecystectomies; incidence was higher after open (n = 51, 4.93%) versus
laparoscopic procedures (n = 421, 0.64%; P < .001). Independent risk factors for
SSI included male gender, preoperative chronic anemia, diabetes, drug abuse,
malnutrition/weight loss, obesity, smoking-related diseases, previous
Staphylococcus aureus infection, laparoscopic approach with acute
cholecystitis/obstruction (hazards ratio [HR], 1.58; 95% confidence interval
[CI], 1.27-1.96), open approach with (HR, 4.29; 95% CI, 2.45-7.52) or without
acute cholecystitis/obstruction (HR, 4.04; 95% CI, 1.96-8.34), conversion to open
approach with (HR, 4.71; 95% CI, 2.74-8.10) or without acute
cholecystitis/obstruction (HR, 7.11; 95% CI, 3.87-13.08), bile duct exploration,
postoperative chronic anemia, and postoperative pneumonia or urinary tract
infection. CONCLUSIONS: Acute cholecystitis or obstruction was associated with
significantly increased risk of SSI with laparoscopic but not open
cholecystectomy. The risk of SSI was similar for planned open and converted
procedures. These findings suggest that stratification by operative factors is
important when comparing SSI rates between facilities.
PMID- 28491888
TI - Successful Treatment of Allergic Bronchopulmonary Aspergillosis With
Isavuconazole: Case Report and Review of the Literature.
AB - Isavuconazole is a new triazole that is approved for primary therapy of invasive
aspergillosis. We provide the first report of a patient with allergic
bronchopulmonary aspergillosis (ABPA) who was successfully treated with
isavuconazole with marked improvement and minimal adverse effects. We further
review the literature on antifungal management of ABPA.
PMID- 28491890
TI - Dengue Virus Entry and Replication Does Not Lead to Productive Infection in
Platelets.
AB - Thrombocytopenia is a characteristic feature during the acute phase of dengue
infection and has been found to associate with vascular leakage in severe dengue.
Although dengue antigens have been observed in platelets, there is no strong
evidence to suggest a direct infection of platelets by dengue virus as a
contributing factor for thrombocytopenia. We show that dengue virus can enter
platelets but replicate viral ribonucleic acid to a minimal extent and,
therefore, cannot produce infectious virus. Dengue antigen was undetectable in
platelets isolated from dengue patients; however, we observed an increase in
CD14+CD16+ monocyte-platelet complexes, suggesting a mechanism for platelet
clearance.
PMID- 28491889
TI - Infections in Hematopoietic Cell Transplant Recipients: Results From the Organ
Transplant Infection Project, a Multicenter, Prospective, Cohort Study.
AB - BACKGROUND: Infection is a major cause of morbidity and mortality after
allogeneic hematopoietic cell transplantation (HCT). Our object was to better
define the epidemiology and outcomes of infections after HCT. METHODS: This was a
prospective, multicenter cohort study of HCT recipients and conducted from 2006
to 2011. The study included 4 US transplant centers and 444 HCT recipients. Data
were prospectively collected for up to 30 months after HCT using a standardized
data collection tool. RESULTS: The median age was 53 years, and median follow up
was 413 (range, 5-980) days. The most common reason for HCT was hematologic
malignancy (87%). The overall crude mortality was 52%. Death was due to
underlying disease in 44% cases and infection in 21%. Bacteremia occurred in 231
(52%) cases and occurred early posttransplant (median day 48). Gram-negative
bloodstream infections were less frequent than Gram-positive, but it was
associated with higher mortality (45% vs 13%, P = .02). Clostridium difficile
infection developed in 148 patients (33%) at a median of 27 days post-HCT. There
were 53 invasive fungal infections (IFIs) among 48 patients (11%). The median
time to IFI was 142 days. Of 155 patients with cytomegalovirus (CMV) infection,
4% had CMV organ involvement. Varicella zoster infection (VZV) occurred in 13
(4%) cases and was disseminated in 2. Infection with respiratory viruses was seen
in 49 patients. Pneumocystis jirovecii pneumonia was rare (1%), and there were no
documented cases of nocardiosis, toxoplasmosis, endemic mycoses, or mycobacterial
infection. This study lacked standardized antifungal and antiviral prophylactic
strategies. CONCLUSIONS: Infection remains a significant cause of morbidity and
mortality after HCT. Bacteremias and C difficile infection are frequent,
particularly in the early posttransplant period. The rate of IFI is approximately
10%. Organ involvement with CMV is infrequent, as are serious infections with VZV
and herpes simplex virus, likely reflecting improved prevention strategies.
PMID- 28491891
TI - A Report of Adult Human Adenovirus Infections in a Tertiary Hospital.
AB - We describe a review of human adenovirus (HAdV) infections occurring among adults
in a tertiary hospital in Singapore from February to May 2013. A similar increase
in cases was observed among children and military personnel during the same time
period. The majority of isolates were identified as HAdV-7, likely an emerging
pathogen in Asia.
PMID- 28491892
TI - Evaluation of a Novel Alcohol-Based Surface Disinfectant for Disinfection of Hard
and Soft Surfaces in Healthcare Facilities.
AB - We examined the efficacy of a new 1-step cleaner and disinfectant containing 30%
ethanol that is applied as a spray. The product rapidly reduced vegetative
bacterial pathogens on carriers and on hard and soft surfaces in healthcare
settings, but it did not stain clothing.
PMID- 28491893
TI - Predictors of Dengue-Related Mortality and Disease Severity in a Tertiary Care
Center in North India.
AB - BACKGROUND: There is lack of reliable predictors of disease severity and
mortality in dengue. The present study was carried out to identify these
predictors during the 2015 outbreak in India. METHODS: This prospective
observational study included confirmed adult dengue patients hospitalized between
August and November 2015 in a tertiary care centre in New Delhi, India.
Appropriate statistical tests were used to compare clinicolaboratory
characteristics, derive predictors of severe disease and mortality, and compute a
predictive score for mortality. Serotyping was done. RESULTS: Data of 369
patients were analyzed (mean age, 30.9 years; 67% males). Of these, 198 (54%)
patients had dengue fever, 125 (34%) had dengue hemorrhagic fever (grade 1 or 2),
and 46 (12%) developed dengue shock syndrome (DSS). Twenty-two (6%) patients
died. Late presentation to the hospital (>=5 days after onset) and dyspnea at
rest were identified as independent predictors of severe disease. Age >=24 years,
dyspnea at rest and altered sensorium were identified as independent predictors
of mortality. A clinical risk score was developed (12*age + 14*sensorium +
10*dyspnea), which, if >=22, predicted mortality with a high sensitivity (81.8%)
and specificity (79.2%). The predominant serotypes in Delhi (2015) were dengue
virus DENV2 and DENV4. CONCLUSION: Age >=24 years, dyspnea at rest, and altered
sensorium were identified as independent predictors of mortality. Platelet counts
did not determine outcome in dengue patients. Timely referral/access to
healthcare is important. The clinical risk score for mortality prediction that
was developed in this study can be used in all healthcare settings, after
validation in larger cohorts.
PMID- 28491894
TI - Curative Effects for B-Cell Lymphoma Accomplished by Direct-Acting Antiviral
Agents of Hepatitis C.
AB - Hepatitis C virus (HCV) is a hepatotropic and lymphotropic virus with the
capabilities of tumorigenesis. We present an HCV-infected patient affected with B
cell lymphomas after suffering from hepatocellular carcinoma. The patient
exhibited curative effects for lymphomas after treatment with sofosbuvir and
ledipasvir, which is shown clearly with a positron emission tomography scanner.
PMID- 28491895
TI - Pyogenic Arthritis of the Fingers and the Wrist: Can We Shorten Antimicrobial
Treatment Duration?
AB - BACKGROUND: Pyogenic arthritis of the small joints of the hand and wrist is a
known but poorly described entity. The objective of this work was to characterize
the clinical presentation, antimicrobial treatment, and surgical interventions of
native small joint arthritis (SJA) treated in our tertiary center. METHODS:
According to predefined variables, medical records of adult patients with SJA
treated in a Swiss university hospital between 2005 and 2013 were retrospectively
analyzed. RESULTS: The median age of 97 patients (101 joints) was 52 years
(interquartile range [IQR], 38-68 years); 52% had no comorbidity. Small joint
arthritis of the second and third fingers accounted for 53% of infections, with
metacarpal-phalangeal and proximal interphalangeal joints most commonly involved.
Of 86 (89%) episodes with an exogenous source, 63 (65%) followed a trauma. The
most commonly isolated microorganism was Staphylococcus aureus (38%), followed by
beta-hemolytic streptococci (13%) and Pasteurella spp (11%). Eighty-seven
episodes (89 joints) in patients with follow-up examinations were included in
treatment and outcome analyses. Up to 2 surgical interventions were required to
cure infection in 74 (83%) joints. Median antimicrobial treatment duration was 14
days (IQR, 12-28 days), with amoxicillin/clavulanate administered in 74 (85%)
episodes. At follow up, cure of infection was noted in all episodes and good
functional outcome in 79% of episodes. CONCLUSIONS: Small joint arthritis shows
considerable differences from clinical patterns reported for larger joints. In
our series, the outcome was good with no more than 2 surgical interventions and
median treatment duration of 14 days in 79% of episodes.
PMID- 28491896
TI - Physical activity predicts reduced plasma beta amyloid in the Cardiovascular
Health Study.
AB - OBJECTIVE: Higher levels of physical activity (PA) reduce the risk of cognitive
impairment, but the underlying mechanisms are unclear. Using longitudinal data
from the Cardiovascular Health Study, we examined whether PA predicted plasma
Abeta levels and risk for cognitive decline 9-13 years later. METHODS: Linear and
logistic regressions (controlling for APOE status, age, gender, body mass index,
cardiovascular disease, brain white matter lesions, and cystatin C levels) tested
associations between PA, Abeta, and cognitive impairment in a sample of 149
cognitively normal older adults (mean age 83 years). RESULTS: More PA at baseline
predicted lower levels of Abeta 9-13 years later. Higher Abeta levels at year 9
predicted greater risk for cognitive impairment at year 13. Levels of Abeta at
year 9 mediated the relationship between PA and cognitive impairment.
INTERPRETATION: Greater PA may reduce plasma levels of a neurotoxic peptide at an
age when the risk for cognitive impairment is especially high.
PMID- 28491897
TI - Longitudinal characterization of biomarkers for spinal muscular atrophy.
AB - OBJECTIVE: Recent advances in understanding Spinal Muscular Atrophy (SMA)
etiopathogenesis prompted development of potent intervention strategies and
raised need for sensitive outcome measures capable of assessing disease
progression and response to treatment. Several biomarkers have been proposed;
nevertheless, no general consensus has been reached on the most feasible ones. We
observed a wide range of measures over 1 year to assess their ability to monitor
the disease status and progression. METHODS: 18 SMA patients and 19 healthy
volunteers (HV) were followed in this 52-weeks observational study. Quantitative
MRI (qMRI) of both thighs and clinical evaluation of motor function was performed
at baseline, 6, 9 and 12 months follow-up. Blood samples were taken in patients
for molecular characterization at screening, 9 and 12 month follow-up.
Progression, responsiveness and reliability of collected indices were quantified.
Correlation analysis was performed to test for potential associations. RESULTS:
QMRI indices, clinical scales and molecular measures showed high to excellent
reliability. Significant differences were found between qMRI of SMA patients and
HV. Significant associations were revealed between multiple qMRI measures and
functional clinical scales. None of the qMRI, clinical, or molecular measures was
able to detect significant disease progression over 1 year. INTERPRETATION: We
probed a variety of quantitative measures for SMA in a slowly-progressing disease
population over 1 year. The presented measures demonstrated potential to provide
a closer link to underlying disease biology as compared to conventional
functional scales. The proposed biomarker framework can guide implementation of
more sensitive endpoints in future clinical trials and prove their utility in
search for novel disease-modifying therapies.
PMID- 28491898
TI - A Cross-sectional population-based investigation into behavioral change in
amyotrophic lateral sclerosis: subphenotypes, staging, cognitive predictors, and
survival.
AB - OBJECTIVE: Amyotrophic Lateral Sclerosis (ALS) is a clinically heterogeneous
neurodegenerative disorder associated with cognitive and behavioral impairment.
The primary aim of this study was to identify behavioral subphenotypes in ALS
using a custom designed behavioral assessment tool (Beaumont Behavioural
Inventory, BBI). Secondary aims were to (1) investigate the predictive nature of
cognitive assessment on behavioral change, (2) report the behavioral profile
associated with the C9orf72 expansion, (3) categorize behavioral change through
disease staging, and (4) to investigate the relationship between cross-sectional
behavioral classification and survival. METHODS: A cross-sectional population
based research design was applied to examine behavioral data from ALS patients (n
= 317) and healthy controls (n = 66). Patients were screened for the C9orf72
repeat expansion. A subcohort of ALS patients completed an extensive cognitive
assessment battery (n = 65), to investigate predictors of behavior change.
Principal component analysis (PCA) determined factors associated with altered
behavior. Survival data were extracted from the Irish ALS register. RESULTS: No
behavioral changes were reported in 180 patients (57%); 95 patients had mild
moderate behavioral change (30%); 42 patients met the cut-off for Clinically
Severe Behavioral Change (13%), suggestive of a bvFTD diagnosis. The most
frequently endorsed behaviors in ALS were reduced concern for hygiene (36.8%),
irritability (36.2%), new unusual habits (33.4%), and increased apathy (31.1%).
Five independent factors were identified through factor analysis. Social
cognitive performance was predictive of behavior change (P = 0.031), yielding an
R2 = 0.188. Behavioral categorization (mild/moderate/severe) at the time of
assessment was not associated with survival (P = 0.198). INTERPRETATION: These
data imply the presence of distinct subphenotypes of behavioral change in ALS,
which most likely reflect subcategories of extramotor network disruption.
PMID- 28491900
TI - Screening of conventional anticonvulsants in a genetic mouse model of epilepsy.
AB - OBJECTIVE: Epilepsy is a common neurological disorder that affects 1% of the
population. Approximately, 30% of individuals with epilepsy are refractory to
treatment, highlighting the need for novel therapies. Conventional anticonvulsant
screening relies predominantly on induced seizure models. However, these models
may not be etiologically relevant for genetic epilepsies. Mutations in SCN1A are
a common cause of Dravet Syndrome, a severe epileptic encephalopathy. Dravet
syndrome typically begins in infancy with seizures provoked by fever and then
progresses to include afebrile pleomorphic seizure types. Affected children
respond poorly to available anticonvulsants. Scn1a+/- heterozygous knockout mice
recapitulate features of Dravet syndrome and provide a potential screening
platform to investigate novel therapeutics. In this study, we conducted a
screening of conventional anticonvulsants in Scn1a+/- mice to establish assays
that most closely correlate with human response data. METHODS: On the basis of
clinical response data from a large, single center, retrospective survey of
Dravet syndrome case records, we selected nine drugs for screening in Scn1a+/-
mice to determine which phenotypic measures correlate best with human therapeutic
response. We evaluated several screening paradigms and incorporated
pharmacokinetic monitoring to establish drug exposure levels. RESULTS: Scn1a+/-
mice exhibited responses to anticonvulsant treatment similar to those observed
clinically. Sodium channel blockers were not effective or exacerbated seizures in
Scn1a+/- mice. Overall, clobazam was the most effective anticonvulsant in Scn1a+/
mice, consistent with its effect in Dravet syndrome. INTERPRETATION: Genetic
models of spontaneous epilepsy provide alternative screening platforms and may
augment the AED development process. In this study, we established an effective
screening platform that pharmacologically validated Scn1a+/- mice for preclinical
screening of potential Dravet syndrome therapeutics.
PMID- 28491899
TI - Diagnostic and cost utility of whole exome sequencing in peripheral neuropathy.
AB - OBJECTIVE: To explore the diagnostic utility and cost effectiveness of whole
exome sequencing (WES) in a cohort of individuals with peripheral neuropathy.
METHODS: Singleton WES was performed in individuals recruited though one
pediatric and one adult tertiary center between February 2014 and December 2015.
Initial analysis was restricted to a virtual panel of 55 genes associated with
peripheral neuropathies. Patients with uninformative results underwent expanded
analysis of the WES data. Data on the cost of prior investigations and
assessments performed for diagnostic purposes in each patient was collected.
RESULTS: Fifty patients with a peripheral neuropathy were recruited (median age
18 years; range 2-68 years). The median time from initial presentation to study
enrollment was 6 years 9 months (range 2 months-62 years), and the average cost
of prior investigations and assessments for diagnostic purposes AU$4013 per
patient. Eleven individuals received a diagnosis from the virtual panel. Eight
individuals received a diagnosis following expanded analysis of the WES data,
increasing the overall diagnostic yield to 38%. Two additional individuals were
diagnosed with pathogenic copy number variants through SNP microarray.
CONCLUSIONS: This study provides evidence that WES has a high diagnostic utility
and is cost effective in patients with a peripheral neuropathy. Expanded analysis
of WES data significantly improves the diagnostic yield in patients in whom a
diagnosis is not found on the initial targeted analysis. This is primarily due to
diagnosis of conditions caused by newly discovered genes and the resolution of
complex and atypical phenotypes.
PMID- 28491901
TI - Predictors of clinical recovery from vestibular neuritis: a prospective study.
AB - We sought to identify predictors of symptomatic recovery in vestibular neuritis.
Forty VN patients were prospectively studied in the acute phase (median = 2 days)
and 32 in the recovery phase (median = 10 weeks) with vestibulo-ocular reflex,
vestibular-perceptual, and visual dependence tests and psychological
questionnaires. Clinical outcome was Dizziness Handicap Inventory score at
recovery phase. Acute visual dependency and autonomic arousal predicted outcome.
Worse recovery was associated with a combination of increased visual dependence,
autonomic arousal, anxiety/depression, and fear of bodily sensations, but not
with vestibular variables. Findings highlight the importance of early
identification of abnormal visual dependency and concurrent anxiety.
PMID- 28491902
TI - De novo REEP2 missense mutation in pure hereditary spastic paraplegia.
AB - Alterations in proteins that regulate endoplasmic reticulum morphology are common
causes of hereditary spastic paraplegia (SPG1-78, plus others). Mutations in the
REEP1 gene that encodes an endoplasmic reticulum-shaping protein are well-known
causes of SPG31, a common autosomal dominant spastic paraplegia. A closely
related gene, REEP2, is mutated in SPG72, with both autosomal and recessive
inheritances. Here, we report a patient with a pure hereditary spastic paraplegia
due to a de novo missense mutation (c.119T > G, p.Met40Arg) in REEP2 at a highly
conserved residue very close to another known pathogenic missense change. This
represents only the second autosomal dominant SPG72 missense mutation reported.
PMID- 28491904
TI - Corrigendum.
AB - [This corrects the article DOI: 10.1002/acn3.387.].
PMID- 28491903
TI - Dimethyl fumarate alters B-cell memory and cytokine production in MS patients.
AB - We evaluated the effect of dimethyl fumarate (DMF) treatment on B-cell memory and
cytokine production in 18 patients with relapsing remitting multiple sclerosis
(RRMS) using peripheral blood mononuclear cells obtained prior to and at 6 months
post-DMF initiation. We noted a decline in the absolute B-cell number with DMF
treatment, with a preferential depletion of memory B cells and a concurrent
increase in naive B cells. We noted significant reductions in GM-CSF, TNF-alpha,
and IL-6 producing B cells with DMF treatment. These effects on the B-cell
compartment may underlie the beneficial effects of DMF in RRMS.
PMID- 28491905
TI - Genetically expressed voltage sensor ArcLight for imaging large scale cortical
activity in the anesthetized and awake mouse.
AB - With the recent breakthrough in genetically expressed voltage indicators (GEVIs),
there has been a tremendous demand to determine the capabilities of these sensors
in vivo. Novel voltage sensitive fluorescent proteins allow for direct
measurement of neuron membrane potential changes through changes in fluorescence.
Here, we utilized ArcLight, a recently developed GEVI, and examined the
functional characteristics in the widely used mouse somatosensory whisker
pathway. We measured the resulting evoked fluorescence using a wide-field
microscope and a CCD camera at 200 Hz, which enabled voltage recordings over the
entire cortical region with high temporal resolution. We found that ArcLight
produced a fluorescent response in the S1 barrel cortex during sensory
stimulation at single whisker resolution. During wide-field cortical imaging, we
encountered substantial hemodynamic noise that required additional post hoc
processing through noise subtraction techniques. Over a period of 28 days, we
found clear and consistent ArcLight fluorescence responses to a simple sensory
input. Finally, we demonstrated the use of ArcLight to resolve cortical S1
sensory responses in the awake mouse. Taken together, our results demonstrate the
feasibility of ArcLight as a measurement tool for mesoscopic, chronic imaging.
PMID- 28491906
TI - Mammalian cortical voltage imaging using genetically encoded voltage indicators:
a review honoring professor Amiram Grinvald.
AB - The pioneering work of Amiram Grinvald established voltage-sensitive dye imaging
(VSDI) in the mammalian cortex in the 1980s and inspired decades of cortical
voltage imaging and the associated technological developments. The recent
conception and development of genetically encoded voltage indicators (GEVIs)
overcome many of the limitations of classical VSDI, and open experimental
approaches that provide accruing support for orchestrated neuronal circuit
dynamics of spatially distributed neuronal circuit underlying behaviors. We will
review recent achievements using GEVIs to optically monitor the cortical activity
in mammalian brains in vivo and provide a perspective for potential future
directions.
PMID- 28491907
TI - Comprehensive assessment of patient image quality and radiation dose in latest
generation cardiac x-ray equipment for percutaneous coronary interventions.
AB - This study aimed to determine whether a reduction in radiation dose was found for
percutaneous coronary interventional (PCI) patients using a cardiac
interventional x-ray system with state-of-the-art image enhancement and x-ray
optimization, compared to the current generation x-ray system, and to determine
the corresponding impact on clinical image quality. Patient procedure dose area
product (DAP) and fluoroscopy duration of 131 PCI patient cases from each x-ray
system were compared using a Wilcoxon test on median values. Significant
reductions in patient dose ([Formula: see text]) were found for the new system
with no significant change in fluoroscopy duration ([Formula: see text]);
procedure DAP reduced by 64%, fluoroscopy DAP by 51%, and "cine" acquisition DAP
by 76%. The image quality of 15 patient angiograms from each x-ray system (30
total) was scored by 75 clinical professionals on a continuous scale for the
ability to determine the presence and severity of stenotic lesions; image quality
scores were analyzed using a two-sample [Formula: see text]-test. Image quality
was reduced by 9% ([Formula: see text]) for the new x-ray system. This
demonstrates a substantial reduction in patient dose, from acquisition more than
fluoroscopy imaging, with slightly reduced image quality, for the new x-ray
system compared to the current generation system.
PMID- 28491908
TI - Lack of agreement between radiologists: implications for image-based model
observers.
AB - We tested the agreement of radiologists' rankings of different reconstructions of
breast computed tomography images based on their diagnostic (classification)
performance and on their subjective image quality assessments. We used 102
pathology proven cases (62 malignant, 40 benign), and an iterative image
reconstruction (IIR) algorithm to obtain 24 reconstructions per case with
different image appearances. Using image feature analysis, we selected 3 IIRs and
1 clinical reconstruction and 50 lesions. The reconstructions produced a range of
image quality from smooth/low-noise to sharp/high-noise, which had a range in
classifier performance corresponding to AUCs of 0.62 to 0.96. Six experienced
Mammography Quality Standards Act (MQSA) radiologists rated the likelihood of
malignancy for each lesion. We conducted an additional reader study with the same
radiologists and a subset of 30 lesions. Radiologists ranked each reconstruction
according to their preference. There was disagreement among the six radiologists
on which reconstruction produced images with the highest diagnostic content, but
they preferred the midsharp/noise image appearance over the others. However, the
reconstruction they preferred most did not match with their performance. Due to
these disagreements, it may be difficult to develop a single image-based model
observer that is representative of a population of radiologists for this
particular imaging task.
PMID- 28491909
TI - Fluorescent Detection of Intracellular Nitric Oxide in Staphylococcus aureus.
AB - Nitric Oxide (NO) is a highly-reactive radical gas that can modify a variety of
cellular targets in both eukaryotes and bacteria. NO is produced endogenously by
a wide variety of organisms: For example, as a cell-signaling molecule in mammals
and bacteria via nitric oxide synthase (NOS) enzymes, and as a product of
denitrification. As such, it is of great benefit to NO researchers to be able to
sensitively detect intracellular NO and stable reactive nitrogen species (RNS)
derived from NO. To this end, a protocol for fluorescent detection of
intracellular NO/RNS in biofilm cultures of the Gram-positive pathogen
Staphylococcus aureus has been optimized using the commercially-available cell
permeable fluorescent stain 4-Amino-5-Methylamino-2', 7'-Difluorofluorescein
Diacetate (DAF-FM diacetate). This compound diffuses into cells and intracellular
cleavage by esterase enzymes liberates weakly-fluorescent DAF-FM, which reacts
with NO or other specific RNS to become highly fluorescent (Kojima et al., 1999).
Although quantification of fluorescence is performed using a fluorescent plate
reader, it is envisioned that this protocol could be adapted for intracellular
NO/RNS imaging of S. aureus biofilms by confocal microscopy. Likewise, this
technique could be optimized for the detection of intracellular NO/RNS in other
growth conditions (i.e., planktonic cultures) and/or in other bacteria/archaea.
PMID- 28491910
TI - Social Disadvantage Is Associated With Lower Vitamin D Levels in Older People and
There Is No Surrogate for Its Measurement.
AB - Introduction: There is increasing evidence concerning adverse health consequences
of low vitamin D levels. We determined whether there is any surrogate for
measuring vitamin D in people older than 70 years and the relation between index
of multiple deprivation (IMD) and vitamin D levels. Methods: Blood samples from
241 patients were included in this analysis. Concurrent measurements for 25
hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH), and bone profile are
reported. Results: The prevalence of total vitamin D insufficiency/deficiency
(defined as total vitamin D <50 nmol/L) was 57.5% overall. Even for patients with
vitamin D deficiency, a significant proportion had PTH, normal calcium,
phosphate, and alkaline phosphatase levels. For patients with vitamin D <25
nmol/L, 62.7% had a PTH within reference range, 83.1% had normal serum-adjusted
calcium, 80.6% had normal phosphate, and 85.1% had a normal serum alkaline
phosphatase. With increasing quintiles of IMD, there was a 22% increased risk of
vitamin D deficiency/insufficiency from quintiles 1 to 5, in age- and sex
adjusted logistic regression models (odds ratio [OR] = 1.22, 95% confidence
interval [1.01, 1.47]; p = .034). Conclusion: No other parameter is currently
adequate for screening for vitamin D deficiency in older people. A higher IMD is
associated with lower vitamin D levels in older people.
PMID- 28491911
TI - Navigating Long-Term Care.
AB - Americans over age 65 constitute a larger percentage of the population each year:
from 14% in 2010 (40 million elderly) to possibly 20% in 2030 (70 million
elderly). In 2015, an estimated 66 million people provided care to the ill,
disabled, and elderly in the United States. In 2000, according to the Centers for
Disease Control and Prevention (CDC), 15 million Americans used some form of long
term care: adult day care, home health, nursing home, or hospice. In all, 13% of
people over 85 years old, compared with 1% of those ages 65 to 74, live in
nursing homes in the United States. Transitions of care, among these various
levels of care, are common: Nursing home to hospital transfer, one of the best
studied transitions, occurs in more than 25% of nursing home residents per year.
This article follows one patient through several levels of care.
PMID- 28491912
TI - Association Between Home Visit Programs and Emergency Preparedness Among Elderly
Vulnerable People in New South Wales, Australia.
AB - Objective: The purpose of this study is to examine the association between home
visit programs and emergency preparedness among elderly vulnerable people in New
South Wales, Australia. Method: The study used data acquired from an intervention
program run by emergency agencies and consisted of 370 older people. Seven
emergency outcome measures were examined by adjusting for key demographic
factors, using a generalized estimating equation model, to examine the
association between home visit programs and emergency preparedness. Results: The
study revealed that knowledge demonstrated by participants during visits and post
home visits showed significant improvements in the seven emergency outcome
measures. The odds of finding out what emergencies might affect one's area were
significantly lower among older participants who were born outside Australia and
those who were women. Discussion: The findings suggest that the intervention via
home visits and periodic reminders post these visits may be a useful intervention
in improving emergency preparedness among older people, especially among men and
those who were born outside of Australia. In addition, other reminders such as
safety messaging via mobile or landline telephone calls may also be a
supplementary and useful intervention to improve emergency preparedness among
older people.
PMID- 28491913
TI - Teaching Our Doctors to Care for the Elderly: A Geriatrics Needs Assessment
Targeting Internal Medicine Residents.
PMID- 28491914
TI - Exploring the Housing Needs of Older People in Standard and Sheltered Social
Housing.
AB - Objective: Our home can have a major impact on our physical and mental health;
this is particularly true for older people who may spend more time at home. Older
people in social (i.e., public) housing are particularly vulnerable. Housing
options for older people in social housing include standard design dwellings or
specially designed "sheltered housing." The most suitable housing model should be
identified, with older people consulted in this process. Method: Survey of older
people (aged >=60) living in standard or sheltered social housing. Data were
analyzed using descriptive and inferential statistics in SPSS Version 22.
Results: Overall, 380 surveys were returned (response rate = 47.2%). All older
people had similar housing needs. Those in sheltered housing were more satisfied
with the physical home design and reported more positive outcomes. Older people
in standard housing were less likely to have necessary adaptations to facilitate
aging-in-place. Discussion: Older people in standard housing reported more
disability/illnesses, are worried about the future, and felt less safe at home.
However, few wanted to move, and very few viewed sheltered housing as an
alternative, suggesting limited knowledge about their housing options. Future
social housing designs should be flexible, that is, adaptable to the needs of the
tenants over time.
PMID- 28491915
TI - Expectations Regarding Aging, Physical Activity, and Physical Function in Older
Adults.
AB - Objective: The present study examined how expectations regarding aging (ERA)
influence physical activity participation and physical function. Method: We
surveyed 148 older adults about their ERA (ERA-38), health-promoting lifestyles
(HPLP-II), and self-rated health (RAND-36). We tested the mediating effect of
physical activity on the relationships between ERA and physical function.
Results: Positive expectations were associated with more engagement in physical
activity (B = 0.016, p < .05) and better physical function (B = 0.521, p < .01).
Physical activity mediated the relationship between ERA and physical function (B
= 5.890, p < .01, indirect effect 0.092, CI = [0.015, 0.239]). Discussion: ERA
play an important role in adoption of physically active lifestyles in older
adults and may influence health outcomes, such as physical function. Future
research should evaluate whether attempts to increase physical activity are more
successful when modifications to ERA are also targeted.
PMID- 28491916
TI - Orthoptic Treatment of Convergence Insufficiency in Parkinson's Disease: A Case
Series.
AB - Introduction: This study reports a case series of orthoptic treatment (OT) for
convergence insufficiency (CI) in individuals with Parkinson's disease (PD).
Method: We are reporting two cases of individuals with PD who completed OT for
CI. Both had a confirmed diagnosis of CI, accompanied by CI-type symptomatology.
They each underwent an OT program consisting of three office-based visits and 8
weeks of home-based exercises. Treatment outcome was based on the changes
measured pre- versus post-OT on the near point of convergence, positive fusional
vergences, and symptomatology score. Results: The two participants successfully
completed therapy, gained ability to converge, had fewer symptoms, and were
satisfied with the OT-induced changes they felt in their day-to-day lives.
Conclusion: This case series show that OT for CI in PD is possible. Further
research is required as these results demonstrate that OT has the potential to
improve symptomatic CI in these patients. In the meantime, the positive results
obtained in these two cases should encourage clinicians to consider OT (a therapy
with no/minimal risk) for CI in patients with PD whose quality of life is
affected by this binocular dysfunction.
PMID- 28491917
TI - Understanding the Burden Experienced by Caregivers of Older Adults Who Use a
Powered Wheelchair: A Cross-Sectional Study.
AB - Objective: In this study, we aimed to describe the burden of family caregivers
providing powered wheelchair-related and overall assistance and test the
hypotheses that caregiver burden correlates with participation, wheelchair skills
capacity, anxiety, depression, and social support. Methods: Cross-sectional
study. Participants included 35 family caregivers of powered wheelchair users.
Caregivers were assessed using the Power Mobility Caregiver Assistive Technology
Outcome Measure, Late Life Disability Instrument, Wheelchair Skills Test
Questionnaire for caregivers, Hospital Anxiety and Depression Scale, and
Interpersonal Support Evaluation List-12. Results: The most burdensome powered
wheelchair assistance items were providing verbal hints/directions, needing to be
nearby, anxiety, and fear that user may be harmed. The most burdensome overall
assistance item was feeling limited in recreational/leisure activities. Caregiver
burden was significantly correlated with participation limitations, anxiety,
depression, and social support. Discussion: Caregivers experience burden for
wheelchair-related and overall help, especially psychological burden. Such
results have implications for the type of resources required to support family
caregivers.
PMID- 28491919
TI - Anterior Superior Iliac Spine to the Tibial Tuberosity Length: An Easier,
Accurate, and Faster Method for Predicting Orogastric Tube Length in Neonates-An
Observational Study.
AB - Orogastric tube (OGT) procedures are done in 20% of newborn unit cases. This
study was contemplated to work out a formula to predict OGT length in terms of
femur length in neonates and its agreement to existing standards. In this
observational study, OGT length was estimated using NEMU (nose-ear-mid umbilicus)
in 53 consecutive newborns. Their anterior superior iliac spine to tibial
tuberosity length (AS-TT) was measured and equated using linear regression
analysis in Stata. We further verified the accuracy of the new formula and
comparison of time taken by both the methods. Strong positive correlation was
seen between OGT and AS-TT (r = .88). OGT length was 10.14 + 0.88 AS-TT, which
can be used in neonatal intensive care unit newborns with greater accuracy and
with lesser time than the classical method. Strong agreement levels were seen. AS
TT closely relates to the femur length and can be chosen as a guide as it is
faster when compared to other methods.
PMID- 28491918
TI - The Studying Multiple Outcomes After Aural Rehabilitative Treatment Study: Study
Design and Baseline Results.
AB - Hearing loss may affect critical domains of health and functioning in older
adults. This article describes the rationale and design of the Studying Multiple
Outcomes After Aural Rehabilitative Treatment (SMART) study, which was developed
to determine to what extent current hearing rehabilitative therapies could
mitigate the effects of hearing loss on health outcomes. One hundred and forty
five patients >=50 years receiving hearing aids (HA) or cochlear implants (CI)
were recruited from the Johns Hopkins Department of Otolaryngology-HNS. A
standardized outcome battery was administered to assess cognitive, social,
mental, and physical functioning. Of the 145 participants aged 50 to 94.9 years
who completed baseline evaluations, CI participants had significantly greater
loneliness, social isolation, and poorer hearing and communicative function
compared with HA participants. This study showed that standardized measures of
health-related outcomes commonly used in gerontology appear sensitive to hearing
impairment and are feasible to implement in clinical studies of hearing loss.
PMID- 28491921
TI - A Rare Presentation of Encephalopathy in a 3-Year-Old Child.
PMID- 28491920
TI - Association of Lead Levels and Cerebral Palsy.
AB - Background: Cerebral palsy is a common motor disability in childhood. Raised lead
levels affect cognition. Children with cerebral palsy may have raised lead
levels, further impairing their residual cognitive motor and behavioral
abilities. Environmental exposure and abnormal eating habits may lead to
increased lead levels. Aims and Objectives: To measure blood lead levels in
children with cerebral palsy and compare them with healthy neurologically normal
children. To correlate blood lead levels with environmental factors. Material and
Methods:Design: Prospective case-control study. Setting: Tertiary care hospital.
Participants: Cases comprised 34 children with cerebral palsy, and controls
comprised 34 neurologically normal, age- and sex-matched children. Methods:
Clinical and demographic details were recorded as per proforma. Detailed
environmental history was recorded to know the source of exposure to lead. These
children were investigated and treated as per protocol. Venous blood was
collected in ethylenediaminetetraacetic acid vials for analysis of blood lead
levels. Lead levels were estimated by Schimadzu Flame AA-6800 (atomic absorption
spectrophotometer). Data were analyzed using SPSS version 17. P < .05 was taken
as significant. Results: Mean blood lead levels were 9.20 +/- 8.31 ug/dL in
cerebral palsy cases and 2.89 +/- 3.04 ug/dL in their controls (P < .001). Among
children with cerebral palsy, 19 (55.88%) children had blood lead levels >=5
ug/dL. Lead levels in children with pica were 12.33 +/- 10.02 ug/dL in comparison
to children with no history of pica, 6.70 +/- 4.60 ug/dL (P = .029). No
correlation was found between hemoglobin and blood lead levels in cases and
controls. Conclusion: In our study, blood lead levels are raised in children with
cerebral palsy. However, further studies are required to show effects of raised
levels in these children.
PMID- 28491922
TI - Epidemiology of Invasive Fungal Infections at Two Tertiary Care Neonatal
Intensive Care Units Over a 12-Year Period (2000-2011).
AB - We conducted a retrospective review of 168 patients with invasive fungal
infections from January 2000 to December 2011 in 2 neonatal intensive care units.
Patients with Candida bloodstream infection (BSI, n = 152) were further analyzed.
C albicans was the most common species overall (47%); however, there was an
increase in non-albicans sp from 2006 to 2011. Candida BSI clearance rates were
lower in extremely low birth weight infants (77% vs 93%, P = .01) and in patients
with C albicans infections (77% vs 91%, P = .01). Clearance rates improved from
2000 to 2005 (70% - 90%) to 2006 to 2011 (86% -100%). Combination antifungal use
increased during the later years (73% vs 49%, P < .05) and in patients with end
organ dissemination (83% vs 54%, P < .05). We concluded that extremely low birth
weight infants and C albicans infection are factors associated with nonclearance
of Candida BSI. Successful clearance of Candida BSI improved in 2006 to 2011,
perhaps due to increase in non-albicans species and the use of combination
antifungals.
PMID- 28491923
TI - Risk Factors for Death in Bangladeshi Children Under 5 Years of Age Hospitalized
for Diarrhea and Severe Respiratory Distress in an Urban Critical Care Ward.
AB - Children with diarrhea hospitalized for respiratory distress often have fatal
outcome in resource-limited settings, although data are lacking on risk factors
for death in such children. We sought to evaluate clinical predictors for death
in such children. In this prospective cohort study, we enrolled under-5 children
with diarrhea admitted with severe respiratory distress to the intensive care
unit of Dhaka Hospital of International Centre for Diarhoeal Disease Research,
Bangladesh, from September 2014 through September 2015. We compared clinical and
laboratory characteristics between study children those who died (n = 29) and
those who survived (n = 62). In logistic regression analysis, after adjusting for
potential confounders, the independent predictors for death in children
hospitalized for diarrhea and severe respiratory distress were severe sepsis and
hypoglycemia (P < .05 for all). Thus, recognition of these simple parameters may
help clinicians identify children with diarrhea at risk of deaths in order to
initiate prompt management for the better outcome, especially in resource-poor
settings.
PMID- 28491924
TI - The Nutrient Density of Snacks: A Comparison of Nutrient Profiles of Popular
Snack Foods Using the Nutrient-Rich Foods Index.
AB - Background: Although Americans receive almost a quarter of their daily energy
from snacks, snacking remains a poorly defined and understood eating occasion.
However, there is little dietary guidance about choosing snacks. Families,
clinicians, and researchers need a comprehensive approach to assessing their
nutritional value. Objective: To quantify and compare the nutrient density of
commonly consumed snacks by their overall nutrient profiles using the Nutrient
Rich Foods (NRF) Index 10.3. Methods: NRF Index scores were calculated for the
top 3 selling products (based on 2014 market research data) in different snack
categories. These NRF scores were averaged to provide an overall nutrient-density
score for each category. Results: Based on NRF scores, yogurt (55.3), milk
(52.5), and fruit (30.1) emerged as the most nutrient-dense snacks. Ice cream (
4.4), pies and cakes (-11.1), and carbonated soft drinks (-17.2) emerged as the
most nutrient-poor snacks. Conclusions: The NRF Index is a useful tool for
assessing the overall nutritional value of snacks based on nutrients to limit and
nutrients to encourage.
PMID- 28491925
TI - No Camphor Toxicity in Cambodian Infants.
AB - Thiamine deficiency and beriberi are prevalent in Cambodia, although most infants
with nonspecific clinical symptoms of beriberi, including tachypnea, lack
echocardiographic evidence diagnostic of the disease. Camphor activates transient
receptor potential vanilloid 3 (TRPV3), a nonselective ion channel expressed in
the medial preoptic nucleus of the hypothalamus and thought to be important for
thermo-sensitivity. Because camphorated ointments are used commonly among
Cambodian infants, we hypothesized that topical camphor modulates
thermoregulatory behaviors, causing beriberi-simulating tachypnea, separate from
any influence of thiamine deficiency. We assessed 9 tachypneic and 10 healthy
infants for Tiger Balm use and for presence of camphor in whole blood. However,
no camphor was found in blood from any infants, indicating that camphor is
unrelated to tachypneic illness in Cambodian infants.
PMID- 28491926
TI - A Novel Intragenic SLC16A1 Mutation Associated With Congenital Hyperinsulinism.
PMID- 28491927
TI - Iron Supplements for Infants at Risk for Iron Deficiency.
AB - Professional societies have published recommendations for iron dosing of preterm
neonates, but differences exist between guidelines. To help develop standardized
guidelines, we performed a 10-year analysis of iron dosing in groups at risk for
iron deficiency: IDM (infants of diabetic mothers), SGA (small for gestational
age), and VLBW premature neonates (very low birth weight, <1500 g). We analyzed
iron dosing after red cell transfusions and erythropoiesis-stimulating agents
(ESA). Of IDM, 11.8% received iron in the hospital; 9.8% of SGA and 27.1% of VLBW
neonates received iron. Twenty percent of those who received iron had it started
by day 14; 63% by 1 month. Supplemental iron was stopped after red cell
transfusions in 73% of neonates receiving iron. An ESA was administered to 1677,
of which 33% received iron within 3 days. This marked variation indicates that a
consistent approach is needed, and using this report and a literature review, we
standardized our iron-dosing guidelines.
PMID- 28491928
TI - Pyogenic Granuloma in an Unusual Site.
PMID- 28491929
TI - Dexmedetomidine as an Adjunct to Treat Anticholinergic Toxidrome in Children.
PMID- 28491930
TI - Hypereosinophilic Syndrome With Eosinophilic Gastritis.
PMID- 28491931
TI - Dopamine-System Genes and Cultural Acquisition: The Norm Sensitivity Hypothesis.
AB - Previous research in cultural psychology shows that cultures vary in the social
orientation of independence and interdependence. To date, however, little is
known about how people may acquire such global patterns of cultural behavior or
cultural norms. Nor is it clear what genetic mechanisms may underlie the
acquisition of cultural norms. Here, we draw on recent evidence for certain
genetic variability in the susceptibility to environmental influences and propose
a norm sensitivity hypothesis, which holds that people acquire culture, and rules
of cultural behaviors, through reinforcement-mediated social learning processes.
One corollary of the hypothesis is that the degree of cultural acquisition should
be influenced by polymorphic variants of genes involved in dopaminergic neural
pathways, which have been widely implicated in reinforcement learning. We
reviewed initial evidence for this prediction and discussed challenges and
directions for future research.
PMID- 28491932
TI - Transition to resistance: An unexpected role of the EMT in cancer
chemoresistance.
AB - Two recent studies provide intriguing evidence that challenges the role of the
epithelial-mesenchymal transition (EMT) as a critical mediator of cancer
metastasis, while revealing an unexpected role in cancer drug resistance.1,2
While these findings may not settle the EMT's role in metastasis, these studies
suggest that targeting the EMT may inhibit both cancer metastasis and
chemoresistance.
PMID- 28491934
TI - Data on anti-insulation detection via Point of Thermal Inflexion (PTI) in 1248
cases; 13 climates, four occupancy profiles, six wall configurations and four
insulation levels.
AB - The data in this article are the simulation results of 1248 cases that were
carried out to detect anti-insulation behaviour in the article titled "Anti
insulation mitigation by altering the envelope layers' configuration" (Idris and
Mae, 2017) [1]. These cases are generated by a matrix of 13 climates, 6 envelope
layer configurations, 4 occupancy profiles and 4 levels of insulation thickness.
The data are concerned with the annual cooling and heating loads of these cases.
In addition, the data include the Point of Thermal Inflexion (PTI) values and
their anti-insulation pattern, when PTI is found. The PTI values are compiled in
a single summary file and supplied as well. All These data are shared via this
article where they can be reused in different ways, but mainly for serving
researchers that intend to approach anti-insulation behaviour from different
points of view.
PMID- 28491935
TI - Numerical dataset for analyzing the performance of a highly efficient ultrathin
film CdTe solar cell.
AB - The article comprises numerical data of distinct semiconductor materials applied
in the sketch of a CdTe absorber based ultrathin film solar cell. Additionally,
the contact layer parametric values of the cell have been described also.
Therefore, the simulation has been conducted with data related to the hetero
structured (n-ZnO/n-CdS/p-CdTe/p-ZnTe) semiconductor device and a J-V
characteristics curve was obtained. The operating conditions have also been
recorded. Afterward, the solar cell performance parameters such as open circuit
voltage (Voc), short circuit current density (Jsc), fill factor (FF), and
efficiency (eta) have been investigated and compared with reference cell.
PMID- 28491936
TI - Data on spatiotemporal urban sprawl of Dire Dawa City, Eastern Ethiopia.
AB - The data presented in this paper shows the spatiotemporal expansion of Dire Dawa
City (eastern Ethiopia) and the ensuing land use land cover changes in its peri
urban areas between 1985 and 2015. The data were generated from satellite images
of Thematic Mapper (TM), Enhanced Thematic Mapper-Plus (ETM+) and OLI
(Operational Land Image) with path/raw value of 166/053 by using Arc GIS 10.1
software. The precision of the images was verified by geolocation data collected
from ground control points by using Geographic Positioning System (GPS) receiver.
Four LULC classes (built up area, vegetation, barren land and farmland) with
their respective spatiotemporal dimensions were clearly identified in the
analysis. Built up area had shown an overall annual increment of 15.8% (82 ha per
year) from 517 ha in 1985 to 2976 ha in 2015. Expansion took place in all
directions but it was more pronounced along the main road towards other nearby
towns, recently established business/service areas and the Industrial Park.
Barren land, farmland and vegetation areas showed speedy decline over the years.
PMID- 28491937
TI - Longitudinal multiple sclerosis lesion segmentation data resource.
AB - The data presented in this article is related to the research article entitled
"Longitudinal multiple sclerosis lesion segmentation: Resource and challenge"
(Carass et al., 2017) [1]. In conjunction with the 2015 International Symposium
on Biomedical Imaging, we organized a longitudinal multiple sclerosis (MS) lesion
segmentation challenge providing training and test data to registered
participants. The training data consists of five subjects with a mean of 4.4 (+/
0.55) time-points, and test data of fourteen subjects with a mean of 4.4 (+/
0.67) time-points. All 82 data sets had the white matter lesions associated with
multiple sclerosis delineated by two human expert raters. The training data
including multi-modal scans and manually delineated lesion masks is available for
download. In addition, the testing data is also being made available in
conjunction with a website for evaluating the automated analysis of the testing
data.
PMID- 28491933
TI - Wnt and BMP Signaling Crosstalk in Regulating Dental Stem Cells: Implications in
Dental Tissue Engineering.
AB - Tooth is a complex hard tissue organ and consists of multiple cell types that are
regulated by important signaling pathways such as Wnt and BMP signaling. Serious
injuries and/or loss of tooth or periodontal tissues may significantly impact
aesthetic appearance, essential oral functions and the quality of life.
Regenerative dentistry holds great promise in treating oral/dental disorders. The
past decade has witnessed a rapid expansion of our understanding of the
biological features of dental stem cells, along with the signaling mechanisms
governing stem cell self-renewal and differentiation. In this review, we first
summarize the biological characteristics of seven types of dental stem cells,
including dental pulp stem cells, stem cells from apical papilla, stem cells from
human exfoliated deciduous teeth, dental follicle precursor cells, periodontal
ligament stem cells, alveolar bone-derived mesenchymal stem cells (MSCs), and
MSCs from gingiva. We then focus on how these stem cells are regulated by bone
morphogenetic protein (BMP) and/or Wnt signaling by examining the interplays
between these pathways. Lastly, we analyze the current status of dental tissue
engineering strategies that utilize oral/dental stem cells by harnessing the
interplays between BMP and Wnt pathways. We also highlight the challenges that
must be addressed before the dental stem cells may reach any clinical
applications. Thus, we can expect to witness significant progresses to be made in
regenerative dentistry in the coming decade.
PMID- 28491939
TI - Data on water consumption in streptozotocin-induced diabetic mice by a novel
peach gum-derived polysaccharide.
AB - The data presented in this article are related to the article entitled "The
impact of a novel peach gum-derived polysaccharide on postprandial blood glucose
control in streptozotocin-induced diabetic mice" (Wang et al., 2017) [1].
Polydipsia was one of the most important symptoms of diabetic mellitus (DM) mice,
which showed more water consumption than normal ones. The water consumption of DM
mice in different groups administrated with metformin hydrochloride or a novel
polysaccharide (coded as PGPSD) were exhibited in this article (Fig. 1). The
field data set is made publicly available to enable critical or extended
analyzes.
PMID- 28491938
TI - Synthesis of practical red fluorescent probe for cytoplasmic calcium ions with
greatly improved cell-membrane permeability.
AB - In this data article, we described the detailed synthetic procedure and the
experimental data for the synthesis of a red-fluorescent probe for calcium ions
(Ca2+) with improved water solubility. This Ca2+ red-fluorescent probe CaTM-3 AM
could be applied to fluorescence imaging of physiological Ca2+ concentration
changes in not only live cells, but also brain slices, with high cell-membrane
permeability leading to bright fluorescence in biosamples. The data provided
herein are in association with the research article "The Development of Practical
Red Fluorescent Probe for Cytoplasmic Calcium Ions with Greatly Improved Cell
membrane Permeability" in Cell Calcium (Hirabayashi et al., 2016) [1].
PMID- 28491940
TI - Data on eleven sesquiterpenoids from the cultured mycelia of Ganoderma capense.
AB - The data included in this paper are associated with the research article entitled
"Sesquiterpenoids from the cultured mycelia of Ganoderma capense" [1]. 1H NMR,
13C NMR, DEPT, HSQC, 1H-1H COSY, HMBC, NOESY, HRESIMS, and IR spectra of
Ganodermanol A-H (1-11), together with Mo2(AcO)4-induced CD spectrum of
Ganodermanol A, CD spectra of Ganodermanol D-E were included in the Data in Brief
article. In addition, the cytotoxicities and anti-HIV-1 activity of isolated
compounds were also included in the Data in Brief article.
PMID- 28491941
TI - Dataset of water activity measurements of alcohol:water solutions using a Tunable
Diode Laser.
AB - The data presented in this article are related to the research article entitled
"RH-temperature phase diagrams of hydrate forming deliquescent crystalline
ingredients" (Allan and Mauer, 2017) [1]. The data are water activity
measurements of alcohol:water solutions (methanol:water and ethanol:water
solutions at varying molar ratios) at different temperatures collected using the
Tunable Diode Laser by Decagon Devices. The measured water activities of
ethanol:water solutions were correlated to the initial volumetric ratios to
produce polynomial equations that can be used to calculate the needed initial
volumetric ratios for water activity controlled solutions. The data sets and
polynomial equations are provided to enable extended analyses and applications of
the data and calculations for generating and using controlled water activity
solutions containing alcohol. An example application of these data is described
in the research article mentioned above.
PMID- 28491942
TI - A dataset of multi-contrast population-averaged brain MRI atlases of a
Parkinson's disease cohort.
AB - Parkinson's disease (PD) is a neurodegenerative disease that primarily affects
the motor functions of the patients. Research and surgical treatment of PD (e.g.,
deep brain stimulation) often require human brain atlases for structural
identification or as references for anatomical normalization. However, two
pitfalls exist for many current atlases used for PD. First, most atlases do not
represent the disease-specific anatomy as they are based on healthy young
subjects. Second, subcortical structures, such as the subthalamic nucleus (STN)
used in deep brain stimulation procedures, are often not well visualized. The
dataset described in this Data in Brief is a population-averaged atlas that was
made with 3 T MRI scans of 25 PD patients, and contains 5 image contrasts: T1w
(FLASH & MPRAGE), T2*w, T1-T2* fusion, phase, and an R2* map. While the T1w,
T2*w, and T1-T2* fusion templates provide excellent anatomical details for both
cortical and sub-cortical structures, the phase and R2* map contain bio-chemical
features. Probabilistic tissue maps of whiter matter, grey matter, and
cerebrospinal fluid are provided for the atlas. We also manually segmented eight
subcortical structures: caudate nucleus, putamen, globus pallidus internus and
externus (GPi & GPe), thalamus, STN, substantia nigra (SN), and the red nucleus
(RN). Lastly, a co-registered histology-derived digitized atlas containing 123
anatomical structures is included. The dataset is made freely available at the
MNI data repository accessible through the link
http://nist.mni.mcgill.ca/?p=1209.
PMID- 28491943
TI - Data on spatiotemporal land use land cover changes in peri-urban Addis Ababa,
Ethiopia: Empirical evidences from Koye-Feche and Qilinto peri-urban areas.
AB - Urban expansion is one of the key problems in Ethiopia resulting in displacement
of the rural people inhabiting areas bordering the cities/towns. It is also
resulting in land use land cover (LULC) changes affecting the livelihoods of the
people and the ecosystems [1], [2]. The data presented in this article,
therefore, shows the spatiotemporal LULC changes of peri-urban expansion areas
known as Koye-Feche and Qilinto, around Addis Ababa City (the capital of
Ethiopia). The data were generated from Landsat Thematic Mapper (TM) and Enhanced
Thematic Mapper Plus (ETM+) images (with path/row numbers 168/054) by using ERDAS
EMAGINE 2014 software. The precision of the images was verified by geolocation
data collected from ground control points by using Geographic Positioning System
(GPS) receiver. The data indicate that the built-up areas have increased by
1017.85 ha (10.178 km2) with 89.1%, 58.4%, 47% and 13% decline of plantation
(mostly eucalyptus woodlots), grasslands, riverine vegetation (forestland) and
cropland, respectively, between 1986 and 2016.
PMID- 28491944
TI - Data on cardiovascular and pulmonary diseases among smokers of menthol and non
menthol cigarettes compiled from the National Health and Nutrition Examination
Survey (NHANES), 1999-2012.
AB - This Data in Brief contains results from three different survey logistic
regression models comparing risks of self-reported diagnoses of cardiovascular
and pulmonary diseases among smokers of menthol and non-menthol cigarettes.
Analyses employ data from National Health and Nutrition Examination Survey
(NHANES) cycles administered between 1999 and 2012, combined and in subsets. Raw
data may be downloaded from the National Center for Health Statistics. Results
were not much affected by which covariates were included in the models, but
depended strongly on the NHANES cycles included in the analysis. All three models
returned elevated risk estimates for three endpoints when they were run in
individual NHANES cycles (congestive heart failure in 2001-02; hypertension in
2003-04; and chronic obstructive pulmonary disease in 2005-06), and all three
models returned null results for these endpoints when data from 1999-2012 were
combined.
PMID- 28491945
TI - Reference values for T, B and NK human lymphocyte subpopulations in adults.
AB - The data presented in this paper are reference ranges for frequencies of thirty
eight subpopulations of T, B and NK lymphocytes, established from a cohort of 253
healthy blood donors aged from 19 to 67. When relevant, the influence of age or
sex was taken into account to calculate these reference values. This article is
related to the research article entitled "Influence of age, sex and HCMV
serostatus on blood lymphocyte subpopulations in healthy adults" (Apoil et al.,
2017) [1]. Immunophenotyping data obtained from each individual is made publicly
available for extended analyses.
PMID- 28491947
TI - Welcome to the New International Journal of Women's Dermatology.
PMID- 28491946
TI - Technique of ICG-guided Targeted Compartmental Pelvic Lymphadenectomy (TCL)
combined with Pelvic Peritoneal Mesometrial Resection (PMMR) for locoregional
control of endometrial cancer - A proposal.
AB - *PMMR is a compartment based radical hysterectomy in endometrial cancer.*Pelvic
PMMR may be combined with ICG guided Targeted Compartmental Lymphadenectomy
(TCL).*Video of Pelvic PMMR and TCL technique may be basis for a prospective
study.
PMID- 28491948
TI - The Women's Dermatology Society: Physicians, Leaders, Mentors.
PMID- 28491950
TI - Clinical and bacteriological efficacy of twice daily topical retapamulin ointment
1% in the management of impetigo and other uncomplicated superficial skin
infections.
AB - BACKGROUND: Cutaneous bacterial infections are common in children and adults and
frequently are caused by Staphylococcus aureus (S. aureus). Treatment failures
with topical agents are not uncommon and have been shown to be secondary to
bacterial resistance. OBJECTIVE: To determine clinical and bacteriological
efficacy of retapamulin ointment 1% in treatment of patients with cutaneous
bacterial infections caused by methicillin-resistant S. aureus (MRSA) and other
bacteria. METHODS: Prospective, nonrandomized, uncontrolled, open label, single
center trial conducted between April 2008 and November 2012 that evaluated
efficacy of retapamulin ointment 1% in the treatment of impetigo, folliculitis,
and other minor soft tissue infections in children and adults. Fifty patients,
who presented to a dermatology outpatient clinic and were clinically diagnosed
with impetigo, folliculitis, or minor soft tissue infection suitable for
treatment with a topical antibiotic, were screened. Thirty-eight patients were
enrolled and received treatment: topical retapamulin ointment 1% twice daily for
5 days. Seven patients were MRSA positive and qualified for the primary efficacy
population. One patient withdrew due to an adverse event. Clinical and
microbiological exams were performed at baseline and follow-up 5 to 7 days later
to assess clinical, microbiological, and therapeutic responses. Primary outcome
was clinical response at follow-up in primary efficacy population with MRSA
isolated as the baseline pathogen. Secondary outcomes included clinical,
microbiologic, and therapeutic responses in patients who were culture positive
for any species of bacteria. RESULTS: Clinical response at follow-up in the
primary efficacy population (MRSA-positive patients) was not sufficiently powered
to demonstrate significance; however, outcomes were excellent, with 7 of 7
patients demonstrating clinical success (5 of 7) or clinical improvement (2 of 7)
at follow-up. Barring lack of significance due to small total sample size for
patients who were culture positive for any species of bacteria (n = 35), overall
success rates were favorable for clinical, microbiologic, and therapeutic
responses with values of 66%, 97%, and 69%, respectively. Adverse events (AEs)
were mild or moderate in severity. No serious AEs were reported. CONCLUSION:
Safety profile appears favorable given the low number of AEs. Study design limits
conclusions that can be drawn. Nevertheless, this study supports use of topical
retapamulin 1% ointment in treatment of cutaneous bacterial infections,
particularly those caused by S. aureus, including MRSA.
PMID- 28491949
TI - Autoimmune blistering diseases in females: a review.
AB - The autoimmune blistering diseases (AIBDs) are a group of heterogeneous skin
diseases with autoantibodies directed against structural proteins in the skin. A
new interest in the female bias towards autoimmune diseases in general has led to
our attention to focus on how and why this female bias manifests in AIBD. The
authors aim to review and explore the various aspects of AIBD affecting females
more than males, including the higher prevalence, worse quality of life, and
complex management issues such as pregnancy and lactation.
PMID- 28491951
TI - Retrospective evidence on outcomes and experiences of pregnancy and childbirth in
epidermolysis bullosa in Australia and New Zealand.
AB - BACKGROUND: Pregnancy in epidermolysis bullosa (EB) has not been comprehensively
studied. OBJECTIVE: We aimed to develop a foundational database, which could
provide peri-obstetric advice in EB. METHODS: Survey questionnaires were sent to
obstetricians, unaffected mothers of EB babies, and mothers with EB. Results were
analyzed using chi-square, Fisher exact, and t-tests. RESULTS: Out of 1346
obstetricians surveyed, 195 responded, and only 14 had encountered EB. All
recommended normal vaginal delivery (NVD), except for one elective Caesarean
section (CS). We received responses from 75 unaffected mothers who had delivered
EB babies. They had significantly more complications in their EB pregnancies
compared to their non-EB pregnancies. A further 44 women with various types of EB
who had given birth responded. Most delivered via NVD and had no significant
increase in complications in both their EB and non-EB pregnancies. In both
groups, there were no significant differences in blistering at birth in babies
delivered via NVD and CS. CONCLUSION: In conclusion, most patients with EB who
are capable of giving birth do not have an increased risk for pregnancy-related
complications and NVD appears to be safe. Awareness of this data amongst
obstetricians and dermatologists should lead to improved quality of care for
mothers and babies affected with EB.
PMID- 28491952
TI - Dermatologic conditions in internationally adopted children.
AB - Over 200,000 children have been adopted into United States (US) families from
abroad since the year 2000. Health care providers who care for children adopted
internationally should be aware of the spectrum of illnesses seen in this
population, and should be prepared to encounter potentially unusual situations.
An appreciation for the unique pre-adoption exposures and vulnerabilities
inherent in international adoption is critical for proper diagnosis and treatment
of this heterogeneous group of children. It is important to consider the impact
of potential early childhood stressors such as nutritional, sensory, and
emotional deprivation, trauma and abuse, as well as prenatal exposures to drugs,
alcohol, and infectious diseases. Providers must also take into account
international variation in health care practices, including immunization,
treatment, surgical, and hygiene standards. The differential diagnosis for
cutaneous eruptions in children adopted internationally is broad and must
encompass endemic systemic illnesses with skin manifestations, such as measles,
tuberculosis, leprosy, and congenital syphilis, and primary dermatologic diseases
such as scabies and bacterial and fungal infections. The importance of
maintaining a broad differential and open mind when addressing the dermatologic
needs of these children cannot be overemphasized.
PMID- 28491953
TI - Prevalence of anemia in patients with epidermolysis bullosa registered in
Australia.
AB - BACKGROUND: Anemia is a common complication of epidermolysis bullosa (EB). To
date, no extensive data on the prevalence of anemia in EB patients have been well
characterized worldwide. OBJECTIVE: To determine and to characterize the
prevalence of anemia in the Australian EB population by conducting a
retrospective cross-sectional study. METHODS: All (n = 368) EB patients
registered in the Australasian Epidermolysis Bullosa Registry (AEBR) from 2006 to
2012 were reviewed for pathological evidence of anemia. Patients with EB without
anemia and those without hematological parameters were excluded from the study.
Patients' particulars were separated into pediatric (< 18 years old) and adult
(>= 18 years old) male and female subgroups. RESULTS: One-hundred sixty-nine out
of 368 EB patients had eligible blood results to be analyzed, as milder forms of
EB did not routinely have laboratory testing; 27.8% (n = 47/169) of EB patients
were anemic at any time point in their lifetime. All generalized severe
junctional EB (JEB-GS) cases (100%, n = 4/4); 68.0% (n = 17/25) of recessive
dystrophic EB (RDEB); and 37.5% (n = 6/16) of generalized intermediate JEB (JEB
I) patients were anemic. LIMITATIONS: As EB is an orphan disease, the limited
sample size may have affected the significance of the study result. CONCLUSION:
The high prevalence of anemia seen in RDEB and JEB generalized severe (JEB-GS)
patients in our cohort is similar to those reported in case series.
PMID- 28491955
TI - Oleoma treated with oral colchicine: Report of two cases and review of the
literature.
AB - Oleoma is a non-allergic, foreign body type granulomatous reaction. It appears as
response to oily exogenous substances injected to the dermis or subcutis for
aesthetical purposes. Treatment for localized lesions is surgical. When they are
multiple, steroids may show some result. Newer therapeutic possibilities are
being introduced and colchicine constitutes an alternative that is financially
accessible and safe in moderate doses for certain dermatological illnesses. We
present two women with oleoma on the legs treated with oral colchicine. This
option was due to the extension of the clinical picture, which would not have a
good surgical outcome. There was significant improvement in one patient, while we
had to interrupt the medication in the other because of side effects.
PMID- 28491954
TI - A systematic review of patients with Merkel cell carcinoma of the head and neck
and a negative sentinel lymph node biopsy.
AB - BACKGROUND: A negative sentinel lymph node biopsy (SLNB) from patients with head
and neck Merkel cell carcinoma (HNMCC) may allow the patient to avoid further
adjunctive therapies. However, there is considerable regional variability of
lymphatic drainage from primary sites involving the head and neck, and Merkel
cell carcinoma (MCC) has aggressive biologic behavior. OBJECTIVE: The primary aim
of this systematic review was to document the incidence of regional recurrence
and mortality from HNMCC patients after a negative SLNB. METHODS: A systematic
search of the English literature was conducted via Ovid Medline and Embase from
inception until 2013 and the Cochrane Central Register of Controlled Trials from
1991 to January 2014. RESULTS: Twenty-three studies, with a total of 81 patients
matched the inclusion criteria. The incidence of regional recurrence from the
entire cohort was 12.3%, and there was a 5% mortality rate. The mean follow-up
time, excluding the 30 patients who did not have individual follow-up times
specified, was 32.8 months. LIMITATIONS: This review included studies had
variable follow-up durations and treatments for MCC. CONCLUSIONS: Despite
negative pathologic staging of the neck using SLNB in HNMCC patients, there is
still a high incidence of regional recurrence and mortality, over a short follow
up period.
PMID- 28491957
TI - Maternity and medical leave during residency: Time to standardize?
PMID- 28491956
TI - Nontuberculous mycobacterial infections: a potential complication of cosmetic
procedures.
AB - Interest in surgical and non-surgical cosmetic procedures has increased
significantly over the last few decades. Billions of dollars are spent on these
procedures annually. Although the associated risk is generally low, multiple
cases of skin and soft tissue infections have been reported. Nontuberculous
mycobacteria (NTM), in particular M. chelonae, M. fortuitum, and M. abscessus,
have been increasingly identified as causative of numerous cosmetic procedure
related infections worldwide. This has therefore become a public health concern.
Delays in diagnosis and appropriate management may occur given subtleties in
diagnostic methods. The purpose of this review is to highlight the NTM-related
skin and soft tissue infections associated with more common cosmetic procedures,
describe methods of identification, and outline best treatment practices.
PMID- 28491958
TI - Maternity Leave for Residents and Young Attendings.
PMID- 28491959
TI - Maternity leave: how to make it fairer for all.
PMID- 28491961
TI - Updates in the understanding and treatments of skin and hair disorders in women
of color.
PMID- 28491962
TI - Skin needling as a treatment for acne scarring: An up-to-date review of the
literature.
AB - BACKGROUND: Skin needling is a technique used to improve the appearance of acne
scarring. OBJECTIVE: To comprehensively review the medical literature regarding
skin needling as a treatment for acne scarring. METHODS: A literature search was
performed using the PubMed, Medline, and Embase databases, in addition to
reviewing the bibliographies of relevant articles. RESULTS: Ten studies presented
patients treated with skin needling alone, while eight studies discussed skin
needling in combination with other treatments for acne scarring. All studies
showed improvements in scarring after needling, with 12 reporting statistical
significance. The median number of treatments when needling was used alone was
three, the median duration between treatments was 4 weeks, and the median needle
length used was 1.5 mm. Reported adverse events were infrequent and included post
inflammatory hyperpigmentation, "tram track" scarring, acne, and milia. There
were no reports of bacterial infections. LIMITATIONS: The studies reviewed were
heterogeneous in design and of variable validity, with some not reporting
statistical significance. CONCLUSION: There is moderate evidence to suggest that
skin needling is beneficial and safe for the treatment of acne scarring. However,
double-blinded, randomized controlled trials are required to make more definitive
conclusions.
PMID- 28491960
TI - Updates in the understanding and treatments of skin & hair disorders in women of
color.
AB - Skin of color comprises a diverse and expanding population of individuals. In
particular, women of color represent an increasing subset of patients who
frequently seek dermatologic care. Acne, melasma, and alopecia are among the most
common skin disorders seen in this patient population. Understanding the
differences in the basic science of skin and hair is imperative in addressing
their unique needs. Despite the paucity of conclusive data on racial and ethnic
differences in skin of color, certain biologic differences do exist, which affect
the disease presentations of several cutaneous disorders in pigmented skin. While
the overall pathogenesis and treatments for acne in women of color are similar to
Caucasian men and women, individuals with darker skin types present more
frequently with dyschromias from acne, which can be difficult to manage. Melasma
is an acquired pigmentary disorder seen commonly in women with darker skin types
and is strongly associated with ultraviolet (UV) radiation, genetic factors, and
hormonal influences. Lastly, certain hair care practices and hairstyles are
unique among women of African descent, which may contribute to specific types of
hair loss seen in this population, such as traction alopecia, trichorrhexis
nodosa and central centrifugal cicatricial alopecia (CCCA).
PMID- 28491963
TI - Nail changes in female pemphigus vulgaris patients on immunosuppressive therapy.
AB - BACKGROUND: Pemphigus vulgaris (PV) patients receiving immunosuppressive therapy
may develop nail alterations resulting from infection, skin disorder, or drug
regimen. OBJECTIVE: This study aims to describe nail changes in PV female
patients receiving immunosuppressive therapy and to report the frequency of
associated fungal and bacterial growth in the patients' nails. METHODS: Twenty
five female PV patients who had at least one acquired finger or toenail
abnormality and had been administered at least one immunosuppressive drug were
included in the study. Nail alterations were recorded. Nail scrapings were
collected from abnormal nails for fungal and bacterial examination. RESULTS:
Positive fungal and bacterial cultures were detected in 20 (80%) of patients'
nail samples. Five patients reported nail alterations coinciding with disease
onset, whereas 13 reported nail changes after administration of immunosuppressive
therapy. LIMITATIONS: Lack of a control group (patients on similar
immunosuppressive medications for conditions other than PV) which would have
further supported the findings demonstrated in this observational study.
CONCLUSION: Nail abnormalities in severe PV patients are frequently associated
with fungal and bacterial growth. Immunosuppressive therapy potentially initiates
such changes.
PMID- 28491964
TI - The effect of probiotics on immune regulation, acne, and photoaging.
AB - Probiotics are live micro-organisms that provide a health benefit to the host.
The role of probiotics in the management of disease, as well as immune
modification, has recently experienced a renewed interest in society, as
probiotics can be found in products ranging from yogurt to facial creams. In this
article, we discuss the role of probiotics in the development of the immune
system, the treatment of acne and rosacea, and protection against aging and
photodamage.
PMID- 28491965
TI - Endocrine evaluation of hirsutism.
AB - Hirsutism is defined as excessive terminal hair growth in a male pattern in
females. It typically affects 5 to 10% of reproductive-age women. Excessive hair
growth can often cause significant psychological and emotional distress. As a
result, hirsutism is a common presenting complaint to healthcare professionals,
including dermatologists, as women search for cosmetic and medical solutions to
their problem. Hirsutism results from excess production of androgens, often from
ovarian or adrenal sources. It is typically associated with a metabolic syndrome
like polycystic ovarian syndrome (PCOS), but can be idiopathic or medication
induced. This article provides an endocrine perspective for the evaluation and
management of hirsutism.
PMID- 28491966
TI - Excimer laser therapy and narrowband ultraviolet B therapy for exfoliative
cheilitis.
AB - BACKGROUND: Exfoliative cheilitis is a condition of unknown etiology
characterized by hyperkeratosis and scaling of vermilion epithelium with cyclic
desquamation. It remains largely refractory to treatment, including
corticosteroid therapy, antibiotics, antifungals, and immunosuppressants.
OBJECTIVE: We sought to evaluate the safety and efficacy of excimer laser therapy
and narrowband ultraviolet B therapy in female patients with refractory
exfoliative cheilitis. METHODS: We reviewed the medical records of two female
patients who had been treated unsuccessfully for exfoliative cheilitis. We
implemented excimer laser therapy, followed by hand-held narrowband UVB
treatments for maintenance therapy, and followed them for clinical improvement
and adverse effects. RESULTS: Both patients experienced significant clinical
improvement with minimal adverse effects with excimer laser therapy 600-700
mJ/cm2 twice weekly for several months. The most common adverse effects were
bleeding and burning, which occurred at higher doses. The hand-held narrowband
UVB unit was also an effective maintenance tool. LIMITATIONS: Limitations include
small sample size and lack of standardization of starting dose and dose
increments. CONCLUSION: Excimer laser therapy is a well-tolerated and effective
treatment for refractory exfoliative cheilitis with twice weekly laser treatments
of up to 700 mJ/cm2. Transitioning to the hand-held narrowband UVB device was
also an effective maintenance strategy.
PMID- 28491967
TI - The history of dermatology at the Woman's Medical College of Pennsylvania.
AB - There is little written about the history of women in dermatology. In this paper,
we summarize the information obtained from archival records from the Woman's
Medical College of Pennsylvania, one of the first medical schools for women,
where several of the early prominent women in dermatology obtained their medical
degrees and practiced. Among others, graduates include Rose Hirschler, MD, and
Margaret Gray Wood, MD. The school and its graduates made important contributions
to dermatology and to the advancement of women in the field. The history of women
in dermatology is not well documented, and this historical research provides
background in the biographies of pioneering women in an effort to preserve and
honor their important work.
PMID- 28491969
TI - The German experiment: Health care without female or Jewish doctors.
AB - Jewish and female doctors were not allowed to practice medicine in Germany during
Hitler's rule from 1933 to 1945. Data about the consequences of this on the
health service are difficult to come by, but what information can be gathered
demonstrates a detrimental effect on the nation's health. These data, however,
must be interpreted with consideration to the morbidity and mortality from
violence, death camps, slave labor, and the privations of war. The article
summarizes the history of German health care during this period and also compares
Germany to other nations at that time.
PMID- 28491970
TI - Mentoring and the U.K. Medical Women's Federation.
PMID- 28491968
TI - The immunologic effects of estrogen on psoriasis: A comprehensive review.
AB - BACKGROUND: Immunological changes in pregnancy are associated with improvements
in some pre-existing immune-mediated skin diseases. Estrogen has been
hypothesized to contribute to these changes by creating a shift from Th1 and Th17
to Th2 immunity. As this hypothesis would predict, psoriasis (a primarily Th17
mediated immune disease) tends to improve during pregnancy. However, the precise
mechanism by which estrogen induces immunological change in psoriasis remains
poorly understood. OBJECTIVE: To summarize the immunologic effects of estrogen as
they relate to psoriasis during pregnancy. METHODS: We performed an English
language PubMed search of articles from September 2004 to September 2014
combining the key terms "psoriasis," "estrogen," "autoimmune disease," and
"pregnancy." RESULTS: Estrogen appears to up-regulate Th2 cytokines and down
regulate Th1 and Th17 cytokines. This shift was initially observed in murine
systems, which showed decreased mixed lymphocyte reactions of splenocytes and
increased antibody production during pregnancy. Antigen stimulated splenocytes
produced fewer Th1 cytokines and more Th2 cytokines in pregnant mice. IL17
producing T cells were significantly decreased in healthy pregnancies compared to
non-pregnant controls. LIMITATIONS: This review is limited by the paucity of
studies evaluating immunological changes of psoriasis in pregnancy among human
subjects. CONCLUSIONS: Increased estrogen production in pregnancy is associated
with decreased Th1 and Th17 cytokine production. While estrogen may be
responsible for some of these immune shifts resulting in disease improvement,
there remains no definitive evidence to prove the hypothesis that estrogen is
responsible for such improvement.
PMID- 28491971
TI - Mentorship: A key mission of the Women's Dermatologic Society.
PMID- 28491972
TI - History of Women in Dermatology series.
PMID- 28491973
TI - Dr. Wilma Fowler Bergfeld: A woman of substance, role model, and founder of the
Women's Dermatologic Society.
PMID- 28491974
TI - Skin cancer concerns particular to women.
AB - BACKGROUND: Skin cancer has reached epidemic proportions, with more new cases
diagnosed annually than the combined incidence of cancers of the breast,
prostate, lung, and colon. Estimates show 2 to 3 million new cases of non
melanoma skin cancer (NMSC) every year, and, among women, it is the young
(younger than 45 years) who are disproportionately affected. OBJECTIVE: This
article aims to address questions and concerns pertinent to skin cancer in a
woman-centric way. An updated landscape of causative factors, the latest
detection/treatment methods, and ultimately the preventative measures available
to them are described. METHODS: A broad literature search was conducted using the
PubMed database with search terms focusing on female gender. Additional articles
were identified from cited references. CONCLUSIONS: The published findings on
causation of melanoma skin cancer and non-melanoma skin cancer in females are
outlined, as well as current detection methods and treatment options.
Furthermore, a variety of preventative measures specific to women that can reduce
the chance of being diagnosed with skin cancer are discussed.
PMID- 28491975
TI - Mid-dermal elastolysis: A female-centric disease; case report and updated review
of the literature.
AB - BACKGROUND: Mid-dermal elastolysis (MDE) is a rare, yet well-defined clinical and
histopathologic entity manifested by fine wrinkling of the skin and mid-dermal
loss of elastic fibers. This disease predominantly affects young to middle-aged
Caucasian females and although it has no reported systemic features, it is
psychologically bothersome and can be of great cosmetic concern. METHODS: We
report a case of a healthy 45 year-old female with widespread mid-dermal
elastolysis. A literature search using the search terms "mid-dermal elastolysis,"
"mid dermal elastolysis," "middermal elastolysis," and "elastophagocytosis" was
conducted on Pubmed, using articles published from January 2008 until November
2014 to accompany Gambichler's comprehensive 1977 to 2009 review of mid-dermal
elastolysis. The references of relevant papers were reviewed and further cases
included as appropriate. RESULTS: We review the clinical features and
histological, ultrastructural, and immunohistochemical findings of MDE, as well
as differential diagnoses. There are 13 new publications of MDE since 2008. The
novel findings since Gambichler's review are discussed and pathomechanisms
revisited. Interestingly, given the striking female predominance of MDE, there is
no known hormonal role in its etiology.
PMID- 28491976
TI - Infiltrated papules on the trunk and headaches: A case of actinic granuloma and a
review of the literature.
AB - Actinic granuloma is a rare granulomatous reaction that is more commonly seen in
females and thought to occur as an autoimmune response to actinic damage of
elastic tissue. We discuss a case of a patient with actinic granuloma presenting
with concomitant temporal arteritis. Our case and review of the literature
emphasize the association between actinic granuloma and temporal arteritis, a
serious inflammatory condition that could lead to blindness if misdiagnosed.
PMID- 28491977
TI - De Sanctis-Cacchione syndrome: A case report and literature review.
AB - De Sanctis-Cacchione (DSC) syndrome is one of the rarest, most severe forms of
xeroderma pigmentosum (XP). These patients with XP are of short stature, have
mental disabilities, and develop progressive neurologic degeneration because of a
severe inability to repair damaged DNA. Herein, we will present the case of a 9
year-old boy who had DSC syndrome with microcephaly, severe psychomotor
retardation, ataxia, and hearing loss. The cutaneous manifestations included
giant squamous cell carcinoma (SCC) that covered the eye, multiple facial SCCs,
and pigment changes on sun-exposed areas. In addition, we include a review of
reported rare cases and a brief discussion of disease management.
PMID- 28491978
TI - Update on lichen planus and its clinical variants.
AB - Lichen planus (LP) is an inflammatory skin condition with characteristic clinical
and histopathological findings. Classic LP typically presents as pruritic,
polygonal, violaceous flat-topped papules and plaques; many variants in
morphology and location also exist, including oral, nail, linear, annular,
atrophic, hypertrophic, inverse, eruptive, bullous, ulcerative, lichen planus
pigmentosus, lichen planopilaris, vulvovaginal, actinic, lichen planus-lupus
erythematosus overlap syndrome, and lichen planus pemphigoides. Clinical
presentation of the rarer variant lesions may be largely dissimilar to classic LP
and therefore difficult to diagnose based solely on clinical examination.
However, histopathological examination of LP and LP-variant lesions reveal
similar features, aiding in the proper diagnosis of the disease. Management of LP
and LP variants aims to control symptoms and to decrease time from onset to
resolution; it often involves topical corticosteroids, but varies depending on
the severity and location of the lesion. The literature contains an array of
reports on the variations in presentation and successful management of LP and its
variants. A familiarity with LP and its variants is important in achieving timely
recognition and management of the disease.
PMID- 28491979
TI - The reliability and validity of outcome measures for atopic dermatitis in
patients with pigmented skin: A grey area.
AB - BACKGROUND: Outcome measures for atopic dermatitis (AD) patients with pigmented
skin have neither been developed nor validated. OBJECTIVE: To compare the
reliability and validity of four common AD outcome measures in patients with
various levels of skin darkness. METHOD: The inter- and intra-rater reliability
and construct validity of the EASI (Eczema Area and Severity Index), objective
SCORing Atopic Dermatitis (oSCORAD), Three Items Severity index (TIS) and Six
Areas, Six Sites Atopic Dermatitis (SASSAD) were evaluated in 18 patients of
various levels of skin darkness, using their full body photographs, by five
trained clinicians. RESULTS: The inter-rater reliability intraclass coefficient
(ICCs) and 95% confidence intervals were poor for highly pigmented patients: EASI
-.054(-.200 to .657), oSCORAD -.089(-.206 to .598), TIS -.21(-.24 to .147),
SASSAD -.071(-.200 to .631); fair for mildly pigmented patients: EASI .464(.140
.839), oSCORAD .588(.265-.89), TIS.524(.200-.865), SASSAD .41(.045-.775); and
fair to good for non-pigmented patients: EASI .64(.330-.908), oSCORAD .586(.263
.889), TIS .403(.09-.809), SASSAD .667(.358-.916). Erythema likely contributed to
the inter-rater variability. Construct validity had significant correlations
across all measures in non-pigmented patients, but no correlations in highly
pigmented patients. CONCLUSION: AD outcome measures have poor reliability and
validity in highly pigmented patients, with variations in erythema perception
being a contributor.
PMID- 28491980
TI - Eruptive inflamed seborrheic keratoses in the setting of endometrial
adenocarcinoma.
AB - Eruptive seborrheic keratoses have been reported as a rare paraneoplastic
dermatosis in the setting of internal malignancy, particularly that of the
digestive tract. This case illustrates a patient with a family history of gastric
cancer who presented with an acute eruption of inflamed pruritic seborrheic
keratoses with annular and gyrate erythema, and was found to have endometrial
adenocarcinoma. The inflammatory cutaneous eruption resolved shortly after
surgical removal of the dysplastic uterine tissue. This case demonstrates an
example of a common gynecological malignancy presenting in an uncommon way; in
the absence of uterine bleeding, the patient's skin manifestations in the form of
a paraneoplastic dermatosis prompted timely diagnosis. Thus this case serves to
raise awareness of cutaneous manifestations of a women's health issue, in which
early detection can impact health outcomes.
PMID- 28491981
TI - The women behind the names: Dermatology eponyms named after women.
PMID- 28491983
TI - Botulinum toxin A injection for chronic anal fissures and anal sphincter spasm
improves quality of life in recessive dystrophic epidermolysis bullosa.
AB - We report a 20-year-old female with generalized, severe, recessive dystrophic
epidermolysis bullosa who developed secondary chronic anal fissures. This
resulted in anal sphincter spasm and severe, disabling pain. She was treated with
five botulinum toxin A injections into the internal anal sphincter over a period
of 2 years and gained marked improvement in her symptoms. This case demonstrates
the successful use of botulinum toxin A injections to relieve anal sphincter
spasm and fissuring, with long-term improvement.
PMID- 28491982
TI - What ages hair?
PMID- 28491984
TI - Infection or allergy? The multifaceted nature of vulvar dermatoses.
AB - Chronic dermatitis or pruritus affecting the female genital and perianal skin can
be challenging to properly diagnose and manage. The differential diagnosis
generally includes allergic, inflammatory, infectious, and neoplastic conditions.
We report the case of a 52-year-old woman with a 6-month history of a
progressive, debilitating vulvar and perianal rash that highlights the
multifaceted nature of female genital dermatoses.
PMID- 28491986
TI - Giant skin tag on the labium majorum.
PMID- 28491985
TI - Anti-p200 pemphigoid (anti-laminin-gamma1 pemphigoid) demonstrating pathergy.
AB - Anti-p200 pemphigoid, also called anti-laminin-gamma1 pemphigoid, is a recently
defined entity. First reported in 1996, the incidence is relatively rare, with
approximately 70 reports in the literature. Clinical presentation is
heterogeneous, but the disease most commonly mimics bullous pemphigoid with
urticarial papules, plaques, or tense bullae on the trunk or extremities.
Described here is a case with additional features of pathergy that have not yet
been reported in the literature.
PMID- 28491987
TI - The Inaugural Dermatology Entrepreneurship Conference: Dermatologists and
Partners Enriching the Pipeline for Innovative Products.
PMID- 28491988
TI - Barbara A. Gilchrest: A world-renowned dermatologist and researcher, a great
mentor, an educator, former president of the Society for Investigative
Dermatology, editor-in-chief of The Journal of Investigative Dermatology, and a
devoted friend.
PMID- 28491989
TI - Professor Rona MacKie, Scottish dermatologist and melanoma authority.
PMID- 28491990
TI - What "leaning in together" means to me.
PMID- 28491991
TI - Chaupadi: The affliction of menses in Nepal.
PMID- 28491992
TI - A ten-year comparison of women authorship in U.S. dermatology literature, 1999
vs. 2009.
AB - Women are entering medicine at increasing rates, particularly in dermatology. In
this study, we compared women's influence and status in academic dermatology with
that of men by examining authorship roles in peer-reviewed dermatology
literature. We examined the literature in 2009 and compared that to 10 years
prior (1999). A total of 1399 articles were reviewed, 594 of which met study
criteria and were included in statistical analysis. There was a marked increase
in senior female authorship over a decade (22% vs. 38%, p < 0.001). Female first
authorship increased as well (41% vs. 51%, p < 0.001). In contrast, changes in
male senior and first authorship were not statistically significant. Federal
funding for female senior authors increased over a decade (19% vs. 37%, p =
0.05), and female senior authors in the 2009 cohort were more likely to hold a
dual MD/PhD degree (0% vs. 11%, p = 0.04) or pure PhD degree (11% vs. 27%, p =
0.04). Women are approaching parity with men in terms of authorship in the
dermatology literature, and additional research training and attainment of
federal funding have helped women publish as senior authors.
PMID- 28491993
TI - Understanding the new FDA pregnancy and lactation labeling rules.
PMID- 28491994
TI - Classifying discoid lupus erythematosus: background, gaps, and difficulties.
AB - To inform our ongoing efforts to develop defining features to be incorporated
into a novel set of classification criteria for discoid lupus erythematosus
(DLE), we conducted a literature review using the Ovid MEDLINE database. A search
was performed to identify studies reporting criteria used to distinguish DLE from
other cutaneous lupus erythematosus subtypes. We examined which clinical,
histopathologic, and serologic features have data to support their use as
effective features in distinguishing DLE from other potential disease mimickers
and cutaneous lupus subsets. Through our search, we were also able to identify
gaps that exist in the literature which can inform future directions for research
endeavors. We found that localization of lesions, characteristic features of
damage, and the absence of high titer Ro/SSA antibody seem most effective in
differentiating DLE from other cutaneous lupus erythematosus subtypes.
Histopathologic features and class of immunoreactant deposition appear to be less
helpful.
PMID- 28491995
TI - Dermatologic surgery on the chest wall in patients with a cardiac surgery
history: a review of material that may be encountered intraoperatively, including
potential complications and suggestions for proceeding safely.
AB - BACKGROUND: Thoracic surgical procedures and the use of cardiac devices such as
pacemakers are becoming increasingly prevalent in the population. As such,
dermatologists may have a greater likelihood of encountering previously implanted
or abandoned surgical material in the course of dermatologic surgery on the chest
wall. A basic understanding of the wire types and the tunneling paths utilized in
such procedures is important in accurately anticipating the presence of these
wires to effectively manage any chance encounters. OBJECTIVE: We present a review
on temporary epicardial pacing wires, temporary transvenous pacing wires,
pacemaker leads, and surgical steel sutures in the context of dermatologic
surgery. METHODS: A literature review was performed on frequently used wire
material in patients with a history of cardiac surgery as well as related
dermatologic complications from these materials. RESULTS & CONCLUSION:
Dermatologic surgeons should particularly be aware that temporary epicardial
pacing wires and pacemaker leads are not uncommonly abandoned in the chest wall
of many patients. All patients with a cardiac surgery history should be
questioned about possible retained wires. If wire material is encountered
intraoperatively, immediately stop the procedure and do not attempt further
manipulation of the wire until suggested steps are taken to ascertain the wire
type.
PMID- 28491996
TI - Amyloidosis: A story of how inframammary erosions eclipsed inconspicuous
periorbital ecchymoses.
AB - Systemic amyloidosis is a rare disease that can be rapidly progressive due to
widespread organ involvement. There are well-described renal, cardiac, pulmonary,
neurological, and dermatologic findings. Here, we outline one patient's
experience with the condition from presentation to making the diagnosis. She
presented with pathognomonic dermatologic findings including pinch purpura and
ecchymoses found in the skin folds.
PMID- 28491997
TI - The quality of dermatology consultation documentation in discharge summaries: a
retrospective analysis.
AB - INTRODUCTION: Good quality documentation of dermatology consults in discharge
summaries allows diagnostic and therapeutic plans to be communicated to other
health professionals and ensures that appropriate governmental funds are provided
to dermatology departments. METHODS: A retrospective analysis was performed of
all dermatology consults seen in 2013 at a public tertiary hospital in Sydney,
Australia. RESULTS: Two hundred nineteen discharge summaries related to inpatient
dermatology consultations were analysed; 80.6% of dermatology consults, 72.2% of
skin biopsies, and 57.6% of diagnoses were duly included in the discharge
summaries; 82.5% of the discharge summaries were completed before the discharge.
The accuracy rate of diagnosis documentation was 54.5% and was correlated with
clear dermatology team documentation, the use of a problems list, infectious skin
diseases and junior medical staff authorship. CONCLUSION: This study highlights
the need for improvement in dermatology consult documentation in discharge
summaries. It suggests the use of a problems list in discharge summaries, clarity
in dermatology teams' documentations, and postdischarge follow-up.
PMID- 28491998
TI - Chromated copper arsenate-treated wood: a potential source of arsenic exposure
and toxicity in dermatology.
AB - Arsenic-contaminated drinking water presents a serious health hazard in certain
geographic locations around the world. Chromated copper arsenate, a pesticide and
preservative that was used to pressure treat residential lumber in the United
States beginning in the 1940s and was banned by the Environmental Protection
Agency in 2003, poses a potential source of arsenic exposure and toxicity. In
this study, we review the clinical manifestations of arsenic intoxication with
the focus on dermatologic manifestations. Dermatologists should be aware that
although chromated copper arsenate-treated wood for residential use was banned in
2003, the exposure risk remains. Long-term follow up is necessary to detect
arsenic induced cutaneous and visceral malignancy in patients with history of
arsenic exposure.
PMID- 28491999
TI - Treatment of lateral canthal rhytides with a medium depth chemical peel with or
without pretreatment with onabotulinum toxin type A: a randomized control trial.
AB - BACKGROUND: Combination therapies used to treat the photoaged skin have become
more popular as studies demonstrate greater efficacy and improved clinical
outcomes compared to single treatment modalities. OBJECTIVES: To evaluate the
safety and effectiveness of treating the lateral canthal rhytide complex with a
Jessner's and 35% TCA peel with and without pretreatment with BTX-A. METHODS:
Twenty-six subjects with Fitzpatrick skin types I -III were randomized to receive
treatment of their lateral canthal rhytide complex with a Jessner's and 35% TCA
peel with or without pretreatment with BTX-A. A single blinded dermatologist
assigned a lateral canthal wrinkle score of subjects' at baseline and week 8-10.
RESULTS: Comparison between the two treatment groups demonstrated that the group
receiving combination treatment had significantly greater improvement in wrinkle
reduction as compared to the group only receiving the chemical peel (P =0.002).
In addition, there was no significant association between skin type and treatment
groups (P = 0.11). CONCLUSIONS: These findings suggest that treating the lateral
canthal rhytide complex with a combination of BTX-A followed by Jessner's and 35%
TCA peel is more effective than chemical peel alone. These results are
independent of skin type and demonstrate an additional treatment strategy for
lateral canthal rhytides.
PMID- 28492000
TI - Use of topical imiquimod in the treatment of VIN: a case report and review of the
literature.
AB - Vulvar intraepithelial neoplasia (VIN) is a premalignant disease of the vulvar
squamous epithelium. Standard treatment for VIN lesions is surgical excision.
Alternative therapeutic options for conservative treatment have been sought by
patients to prevent disfigurement and to preserve sexual function. We present
such a patient in whom topical imiquimod was used with a successful outcome.
Imiquimod is effective in the treatment of VIN, as well as convenient, self
administered, and generally well tolerated.
PMID- 28492001
TI - Improving young physician membership and engagement in a dermatology physician
organization: The Women's Dermatologic Society as a case example.
PMID- 28492002
TI - Women's issues in the 2016 presidential election: impact on women in medicine.
PMID- 28492003
TI - Developing classification criteria for discoid lupus erythematosus: an update
from the World Congress of Dermatology 2015 meeting.
AB - Currently, no standardized classification criteria exist for cutaneous lupus
erythematosus. With increased interest in studying cutaneous lupus erythematosus,
specifically discoid lupus erythematosus, it is our aim to apply previously
adopted methods from rheumatology to dermatologic diseases to develop feasible,
validated, and standardized classification criteria useful in both academic and
community practice. Here we report the progress to date to define discoid lupus
erythematosus using clinical, histopathologic, and serologic features by means of
a Delphi method-using a series of iterative questionnaires sent to expert
stakeholders. We present specific updates from the World Congress of Dermatology
2015 meeting, at which a nominal group of expert stakeholders met to discuss the
results of round 1 of the Delphi process to further clarify and harmonize
specific classification items for inclusion into round 2.
PMID- 28492004
TI - Unforeseen ethical challenges for isotretinoin treatment in transgender patients.
PMID- 28492005
TI - Longitudinal melanonychia in an Iranian population: a study of 96 patients.
AB - BACKGROUND: Longitudinal melanonychia (LM) can be a challenging sign since it may
be caused by a wide variety of benign and malignant conditions. Cutaneous
melanoma is the most important cause of LM. Objective: We performed this study to
examine different aspects of LM in Iran, where cutaneous melanoma is rare.
METHODS: In this cross-sectional study, we reviewed medical records and pathology
reports of a total of 96 patients presenting with LM. These patients had been
visited and undergone nail biopsy in Razi Hospital, Tehran University of Medical
Sciences, Tehran, Iran. Demographic, clinical, and pathological data were
recorded. RESULTS: The most common diagnosis was junctional nevi in 28 patients
(29.2%) followed by melanoma in 19 patients (19.8%). Patients had a mean age of
42.4 years (+/- 19.4). The mean ages in the groups with junctional nevi and
melanoma were 33.3 (+/- 19.5) and 51.9 (+/- 17.8), respectively; their difference
was statistically significant (P value = 0.001). Hutchinson's sign was present in
10 patients, 9 of which had melanoma. Also, melanoma was only observed in
patients presenting with a solitary nail lesion. Nails mostly affected by
melanoma were middle fingers of the hands (7 patients) and thumbs (6 patients).
Out of 18 patients with nail dystrophy, 13 (72.2%) were diagnosed with melanoma.
LIMITATIONS: Only patients who have undergone biopsy were studied. CONCLUSION:
Melanoma is an important cause of LM in Iranian patients and should especially be
suspected in older patients who present with a solitary nail lesion on their
middle finger or thumb. Other findings that direct us toward melanoma are
presence of Hutchinson's sign and nail dystrophy.
PMID- 28492006
TI - Evaluation of prolactin levels in patients with newly diagnosed pemphigus
vulgaris and its correlation with pemphigus disease area index.
AB - BACKGROUND: Prolactin is a hormone; in addition to it known roles, it has
immunomodulatory effects on lymphocytes maturation and immunoglobulins
production. Hyperprolactinemia has been demonstrated in various autoimmune
diseases such as systemic lupus erythematosus, rheumatoid arthritis, type I
diabetes mellitus, and Graves' disease. In view of the prolactin immunomodulatory
roles, studying prolactin levels in pemphigus as an autoimmune blistering disease
may introduce new ways of understanding disease etiology and developing treatment
strategies. OBJECTIVE: Our purpose was to determine the prolactin levels in
patients with newly diagnosed pemphigus vulgaris and study its correlation with
pemphigus disease area index. LIMITATION: Our study was limited by the lack of a
control group. METHODS: In this cross-sectional study, prolactin and anti
desmoglein 1 and 3 autoantibodies levels were measured in 50 patients with newly
diagnosed pemphigus vulgaris in Razi Dermatology Hospital. Pemphigus severity and
extent was estimated using the Pemphigus Disease Area Index. RESULTS: Of the 50
patients, 18 were male and 32 were female with a mean age of 41.56 +/- 13.66
years. Mean prolactin (PRL) level was 15.60 +/- 11.72 ng/ml (10.68 in males and
18.37 in females). Mean anti-desmoglein 1 and 3 autoantibodies were 135.8 +/-
119.8 and 245.8 +/- 157.4 U/ml, respectively. Eleven out of 50 patients had a
higher than normal prolactin range. No relation was found between prolactin level
and disease activity (p = .982). Also, correlation studies show no relation
between prolactin and anti-desmoglein 1 and 3 autoantibodies levels
(respectively, p = .771 and .738). In comparing the extent of the disease between
the two groups with normal and high prolactin, paired t-test showed no
significance (p = .204). CONCLUSION: In our study, 22% of patients had
hyperprolactinemia, which was greater among females. The highest PRL level was
detected in mucocutaneous group. Although serum PRL levels were higher in
patients with a greater Pemphigus Disease Area Index, it did not reach
statistical significance.
PMID- 28492007
TI - Colchicine may assist in reducing granulation tissue in junctional epidermolysis
bullosa.
AB - Epidermolysis bullosa (EB) is a rare, inherited blistering genodermatosis.
Patients with junctional EB (JEB) due to LAMB3 mutations have widespread blisters
and erosions of skin, mucosae, and nails, creating significant physical,
emotional, and psychosocial burdens. Here we report the use of colchicine for
ameliorating hypergranulating wounds in a 41-year-old female with JEB generalized
intermediate. Her skin wounds and granulation tissue gradually exacerbated under
silicone dressings such that she became profoundly anemic. Subsequently, she was
commenced on colchicine 500 MUg daily on the basis that it may inhibit cell
proliferation and be anti-inflammatory. After a 6-month trial of colchicine, she
had an objective and subjective improvement in her validated EB Disease Activity
and Scarring Index activity and damage scores and Quality Of Life in EB score
with less skin erosions, granulation tissue, and erythema. In addition, her
anemia resolved. She denied any gastrointestinal side effects. The exact
mechanism of colchicine in assisting reduction of the blistering, erosions, and
granulation in JEB is unclear, but the anti-inflammatory and antimitotic
properties of colchicine may be partially responsible for this process.
PMID- 28492008
TI - Physician-Industry Collaboration: Organizational Considerations for the Future of
Innovation and Growth in Dermatology.
AB - The U.S. medical environment continues to evolve with issues from Privacy to EMR,
Insurance regulations, Physician Access and Healthcare Reform, and MACRA
(Medicare Access and CHIP Reauthorization Act) on the discussion table. Not since
the advent of Medicare and Medicaid in the mid 1960's, have we seen such
widespread changes in the medical healthcare environment (Centers for Medicare
and Medicaid Services). Physicians, industry, patients and consumers are affected
by the changes. These four groups have historically worked as separate entities,
but are now key stakeholders in the future of dermatology. As stakeholders
collaborating in building a future together, the dermatologists/physicians will
help to ensure and preserve the quality of patient care and best patient
outcomes. In the Executive Forum, leaders from the Women's Dermatologic Society
and Industry, explored five important areas: 1) A five-year outlook of
Dermatology and Medicine; 2) Access of Industry to Dermatologists and Trainees;
3) The New Practice Environment; 4) Doing Things Differently; and 5) Unmet
Specialty Needs. The collaborative group explored solutions for our specialty and
the patients we serve.
PMID- 28492009
TI - Considerations on biologic agents in psoriasis with the new pregnancy lactation
labeling rule.
PMID- 28492010
TI - A case of Stevens-Johnson syndrome with gross hematuria.
PMID- 28492011
TI - The good, the bad, and the ugly of medication coverage: Is altering a diagnosis
to ensure medication coverage ethical?
AB - Recently, a patient presented to the dermatology clinic suffering from disabling,
recurrent palmoplantar vesicles and pustules. Biopsy demonstrated nondiagnostic
histologic findings without unequivocal evidence for psoriasis. The localized
rash was recalcitrant to a host of standard therapies. An anti-tumor necrosis
factor biologic was considered, and experience suggested that this expensive
medication would only be approved for coverage if a diagnosis was submitted for a
Food and Drug Administration-approved indication as psoriasis. All health-care
providers face similar dilemmas in caring for their own patients. To whom is the
physician's primary responsibility when what is best for the patient may not
align with the realities of our health-care system? Should a physician alter or
exaggerate a medical diagnosis to obtain insurance coverage for a needed
medication? What are the ethical implications of this action? If the physician's
fiduciary duty to the patient had no limits, there would be multiple potential
consequences including compromise of the health-care provider's integrity and
relationships with patients, other providers, and third-party payers as well as
the risk to an individual patient's health and creation of injustices within the
health-care system.
PMID- 28492012
TI - Gray Hair, Silver Linings, and the WDS.
PMID- 28492014
TI - Woman, mother, and scientist: Aiming to fulfill a career in research while
maintaining a "good-enough" work-life balance.
PMID- 28492013
TI - Patient and practitioner satisfaction with tele-dermatology including Australia's
indigenous population: A systematic review of the literature.
AB - BACKGROUND: Australia's health disparity, combined with evolving technologies,
has evoked increasing interest and funding in health services that could address
inequities. One such emerging service is tele-medicine. OBJECTIVE: The purpose of
this report is to discuss and evaluate the current literature regarding patient
and practitioner satisfaction with tele-medicine, and more specifically tele
dermatology. METHODS: We searched for literature relevant to tele-dermatology use
among Australia's indigenous population. We synthesized the literature in our
report and identified elements of tele-dermatology not yet researched. RESULTS:
Most significantly, all available research is currently based on descriptive
studies and there is no validated tool to assess the efficacy of tele
dermatology. LIMITATIONS: No published research currently exists on the use of
tele-dermatology among Australia's indigenous population. CONCLUSION: A review of
the literature shows that tele-dermatology is considered a valuable service,
particularly to patients living in rural areas who might not otherwise have
access to specialist care.
PMID- 28492015
TI - A dermatologist guide to immunogenicity.
AB - Dermatologists should be aware that autoantibody formation may occur after the
initiation of biologic therapy. This phenomenon has been referred to as
immunogenicity and biologic fatigue. Because of this, patients may experience
loss of clinical efficacy to a particular drug. To combat this phenomenon, low
dose immunomodulators may be used in hopes of preventing autoantibodies. We
review the current literature and provide a basic treatment algorithm for
patients with moderate to severe psoriasis.
PMID- 28492016
TI - Vaginal rejuvenation using energy-based devices.
AB - Physiologic changes in a woman's life, such as childbirth, weight fluctuations,
and hormonal changes due to aging and menopause, may alter the laxity of the
vaginal canal, damage the pelvic floor, and devitalize the mucosal tone of the
vaginal wall. These events often lead to the development of genitourinary
conditions such as stress urinary incontinence; vaginal atrophy; dryness; and
physiologic distress affecting a woman's quality of life, self-confidence, and
sexuality. Various treatment modalities are currently available to manage these
indications, varying from invasive vaginal surgery to more benign treatments like
topical vaginal hormonal gels or hormone-replacement therapy. A new trend gaining
momentum is the advent of energy-based devices for vaginal rejuvenation that
apply thermal or nonthermal energy to the various layers of the vaginal tissue,
stimulating collagen regeneration contracture of elastin fibers,
neovascularization, and improved vaginal lubrication. This review aims to present
the available technologies offering vaginal rejuvenation and the scientific
evidence that underlines their safety and efficacy for this indication.
PMID- 28492017
TI - Ecthyma gangrenosum secondary to methicillin-sensitive Staphylococcus aureus.
AB - Ecthyma gangrenosum (EG) is a well-described skin manifestation of Pseudomonas
aeruginosa septicemia in immunocompromised patients. However, it can be seen in
association with other bacteria, viruses, and fungi. We report a case of a 54
year-old African American female with metastatic gastric adenocarcinoma and
recent chemotherapy and neutropenia who developed EG-like lesions due to
methicillin-susceptible Staphylococcus aureus. We also review the literature to
evaluate all reported cases of S aureus-associated EG and their clinical
presentation, diagnosis, and treatment.
PMID- 28492018
TI - Impact of leishmaniasis in women: a practical review with an update on my ISD
supported initiative to combat leishmaniasis in Yemen (ELYP).
AB - Stigma is synonymous with leishmaniasis, an endemic deadly flesh-eating disease
in Yemen that affects predominantly poor rural women and children. Women with
leishmaniasis often present late and experience not only physical deformities and
the risk of death, but also the painful stigma of the disease and its
consequences, a similar situation to that of leprosy decades ago. The
International Society of Dermatology-sponsored community dermatology project
Eradication of Leishmaniasis from Yemen Project has made a difference in the
leishmaniasis situation in Yemen and addressed its magnitude. The program
eradicated leishmaniasis from some areas, dealt with and improved its alarming
prevalence among children and women who are the neglected and highest risk
groups, and solved some issues associated with poor access to proper drugs.
Medicine donation has enabled women with leishmaniasis to freely receive medicine
they otherwise would not have been able to afford, reduced their mortality and
morbidity, and minimized the extensive impact the socio-aesthetic stigma has on
their lives. Our cause has attracted local and global attention to these
problematic issues.
PMID- 28492019
TI - Dr. Maureen Rogers, the first Australian pediatric dermatologist.
PMID- 28492021
TI - A lesson learned about predatory journals and their difference from peer-reviewed
open-access publishing.
PMID- 28492020
TI - Helen Ollendorff-Curth: A dermatologist's lasting legacy.
PMID- 28492022
TI - Medical publishing and the threat of predatory journals.
PMID- 28492023
TI - Leprosy and women.
AB - Leprosy has an impact on the physical, social, and psychological health of
affected people. Women in developing countries seek health care late for any
health-related issues. Leprosy, a disease known for its stigma, adds further to
these facts. Also, close contact between women and family members, especially
children, increases the chance of transmission to others and thereby increases
the disease burden in the society. Hence, leprosy in women is an important issue
for the affected patient, their family members, and society as a whole.
PMID- 28492024
TI - Hair camouflage: A comprehensive review.
AB - Hair is venerated, cherished, and desired in societies throughout the world. Both
women and men express their individual identities through their hairstyles.
Healthy hair contributes to successful social assimilation, employment, and
overall quality of life. Therefore, hair loss can have detrimental effects on
almost every aspect of a person's life. In this review, we discuss the myriad of
options that aid in concealing and camouflaging hair loss to facilitate a
healthier-appearing scalp. Camouflage options for patients who suffer from hair
loss include full or partial wigs, hair extensions, concealing powders and
sprays, surgical tattoos, and hair transplants. We describe these modalities in
detail and discuss their respective advantages and disadvantages.
PMID- 28492025
TI - Validation studies of outcome measures in pemphigus.
AB - Pemphigus is a group of rare and potentially fatal autoimmune blistering diseases
that are associated with auto-antibodies that target intercellular adhesion
molecules. Incidence of pemphigus varies among populations, with the lowest
incidence in Switzerland and Finland at 0.6-0.76 per million per year and the
highest in Jewish communities at 16.1-32 per million per year. Pemphigus is
associated with devastating morbidity and despite advancements in our
understanding of the disease and a widening array of therapeutic options, no cure
exists. The delay in the development of a cure may in part be attributed to the
absence of a standardized and completely validated severity outcome measures to
allow for high-quality multicenter control studies. Such a tool is necessary to
define the best practice in clinical studies, allow for accurate comparisons
between study results, justify drug use within the clinical setting, and reduce
the cost burden that is associated with the use of ineffective therapies.
Utilizing outcome measures that are not validated provides an opportunity to
synthesize outcome measures with the intent to favor particular treatments and
thus produce false conclusions. According to the COnsensus-based Standards for
the selection of health Measurement INstruments (COSMIN) group, a validation of
these measurement instruments requires investigating their responsiveness,
reliability, and validity. More than 116 outcome measures exist to assess
pemphigus severity, of which the Pemphigus Disease Area Index (PDAI), Autoimmune
Bullous Skin Disorder Intensity Score (ABSIS), and Pemphigus Vulgaris Activity
Score (PVAS) are the most comprehensively corroborated measures. With regard to
validity and reliability, PDAI was unsurpassed by ABSIS and PVAS. Data indicate
that ABSIS is more reliable than PVAS, but PVAS seems to have greater validity
although the results are not consistent. PDAI, ABSIS, and PVAS have not yet had
their responsiveness analyzed, which should be the next step to completely
validate the outcome measures and conclusively determine which measure is
superior.
PMID- 28492026
TI - Acral self-healing collodion baby: A case series.
AB - Collodion baby is a term used to describe a phenotype characterized by the
presence of a tight, translucent membrane that covers the entire skin at birth.
This membrane usually sheds around 10 to 14 days and reveals the underlying
disease (mainly different types of Recessive Ichthyosis or other infrequent
disorders). A rare variant of this phenotype is known as acral self-healing
collodion baby whereby the patients are born with the typical membrane but
limited to the hands and feet only, and after it sheds, the skin appears
completely normal. We report five cases of this very rare subtype of collodion
baby. All the patient cases that are presented involved both hands and feet. One
of the patients also had the umbilicus embedded in a subtle collodion membrane.
None of the patients had a family history of the same entity or any other type of
ichthyosis. In all patients, the condition resolved spontaneously within a few
weeks and no patients developed any other manifestation. Although no molecular
analysis was performed, we contribute to the knowledge of the clinical features
of this extremely uncommon and benign entity, since to the best of our knowledge
there are only two previous reports available in literature.
PMID- 28492027
TI - Tinea corporis in a wrestling team cheerleader.
PMID- 28492028
TI - Professor Claudine Blanchet-Bardon: French dermatologist and leading authority on
inherited ichthyoses.
AB - This article recounts the early life and professional achievements through 2016
of Professor Claudine Blanchet-Bardon, a French dermatologist who is known for
her work in dermatogenetics, genetic counseling, and the care of patients with
ichthyoses among other important work.
PMID- 28492029
TI - Billing and up coding: What's a doctor-patient to do?
PMID- 28492030
TI - Managing the dose escalation of biologics in an era of cost containment: the need
for a rational strategy.
AB - Although biologic medications have demonstrated great efficacy for the treatment
of psoriasis, a subset of patients fails to respond and others lose response
later in the course. In treating a patient who has failed to respond to biologic
therapy, clinicians must decide between dose escalation, switching biologics, and
adding or switching to a non-biologic systemic drug or phototherapy. Although
dose escalation is perhaps the simplest strategy and generally well-tolerated, it
confers a tremendous cost burden because doubling the dosage is likely to double
the wholesale price. We call for the development of rational strategies for the
pricing of dose escalation in order to minimize this phenomenon. We also call for
increased transparency surrounding negotiated pricing to ensure that all patients
have access to the most effective, affordable treatment options available.
PMID- 28492031
TI - Retrospective evidence on outcomes and experiences of pregnancy and childbirth in
epidermolysis bullosa in Australia and New Zealand.
AB - BACKGROUND: Pregnancy in epidermolysis bullosa (EB) has not been comprehensively
studied. OBJECTIVE: We aimed to develop a foundational database, which could
provide peri-obstetric advice in EB. METHODS: Survey questionnaires were sent to
obstetricians, unaffected mothers of EB babies, and mothers with EB. Results were
analyzed using chi-square, Fisher exact, and t-tests. RESULTS: Out of 1346
obstetricians surveyed, 195 responded, and only 14 had encountered EB. All
recommended normal vaginal delivery (NVD), except for one elective Caesarean
section (CS). We received responses from 75 unaffected mothers who had delivered
EB babies. They had significantly more complications in their EB pregnancies
compared to their non-EB pregnancies. A further 44 women with various types of EB
who had given birth responded. Most delivered via NVD and had no significant
increase in complications in both their EB and non-EB pregnancies. In both
groups, there were no significant differences in blistering at birth in babies
delivered via NVD and CS. CONCLUSION: In conclusion, most patients with EB who
are capable of giving birth do not have an increased risk for pregnancy-related
complications and NVD appears to be safe. Awareness of this data amongst
obstetricians and dermatologists should lead to improved quality of care for
mothers and babies affected with EB.
PMID- 28492032
TI - Endocrine evaluation of hirsutism.
AB - Hirsutism is defined as excessive terminal hair growth in a male pattern in
females. It typically affects 5 to 10% of reproductive-age women. Excessive hair
growth can often cause significant psychological and emotional distress. As a
result, hirsutism is a common presenting complaint to healthcare professionals,
including dermatologists, as women search for cosmetic and medical solutions to
their problem. Hirsutism results from excess production of androgens, often from
ovarian or adrenal sources. It is typically associated with a metabolic syndrome
like polycystic ovarian syndrome (PCOS), but can be idiopathic or medication
induced. This article provides an endocrine perspective for the evaluation and
management of hirsutism.
PMID- 28492034
TI - Mentoring and the U.K. Medical Women's Federation.
PMID- 28492033
TI - Cutaneous melanoma in women.
AB - BACKGROUND: Gender disparity in melanoma outcome is consistently observed,
suggesting that gender is as an important prognostic factor. However, the source
of this gender disparity in melanoma remains unclear. OBJECTIVE: This article
reviews advances in our understanding of gender differences in melanoma and how
such differences may contribute to outcomes. METHODS: A broad literature search
was conducted using the PubMed database, with search terms such as 'gender
differences in melanoma' and 'sex differences in melanoma.' Additional articles
were identified from cited references. RESULTS: Herein, we address the gender
linked physiologic differences in skin and melanoma. We discuss the influence of
estrogen on a woman's risk for melanoma and melanoma outcomes with regard to
pregnancy, oral contraceptives, hormone replacement therapy, and UV tanning.
CONCLUSIONS: The published findings on gender disparities in melanoma have
yielded many advances in our understanding of this disease. Biological,
environmental, and behavioral factors may explain the observed gender difference
in melanoma incidence and outcome. Further research will enable us to learn more
about melanoma pathogenesis, with the goal of offering better treatments and
preventative advice to our patients.
PMID- 28492035
TI - The German experiment: health care without female or Jewish doctors.
AB - Jewish and female doctors were not allowed to practice medicine in Germany during
Hitler's rule from 1933 to 1945. Data about the consequences of this on the
health service are difficult to come by, but what information can be gathered
demonstrates a detrimental effect on the nation's health. These data, however,
must be interpreted with consideration to the morbidity and mortality from
violence, death camps, slave labor, and the privations of war. The article
summarizes the history of German health care during this period and also compares
Germany to other nations at that time.
PMID- 28492038
TI - Dr. Wilma Fowler Bergfeld: A Woman of Substance, Role Model, and Founder of the
Women's Dermatologic Society.
PMID- 28492037
TI - The women behind the names: Dermatology eponyms named after women.
PMID- 28492039
TI - Skin cancer concerns particular to women.
AB - BACKGROUND: Skin cancer has reached epidemic proportions, with more new cases
diagnosed annually than the combined incidence of cancers of the breast,
prostate, lung, and colon. Estimates show 2 to 3 million new cases of non
melanoma skin cancer (NMSC) every year, and, among women, it is the young
(younger than 45 years) who are disproportionately affected. OBJECTIVE: This
article aims to address questions and concerns pertinent to skin cancer in a
woman-centric way. An updated landscape of causative factors, the latest
detection/treatment methods, and ultimately the preventative measures available
to them are described. METHODS: A broad literature search was conducted using the
PubMed database with search terms focusing on female gender. Additional articles
were identified from cited references. CONCLUSIONS: The published findings on
causation of melanoma skin cancer and non-melanoma skin cancer in females are
outlined, as well as current detection methods and treatment options.
Furthermore, a variety of preventative measures specific to women that can reduce
the chance of being diagnosed with skin cancer are discussed.
PMID- 28492036
TI - Updates in the understanding and treatments of skin & hair disorders in women of
color.
AB - Skin of color comprises a diverse and expanding population of individuals. In
particular, women of color represent an increasing subset of patients who
frequently seek dermatologic care. Acne, melasma, and alopecia are among the most
common skin disorders seen in this patient population. Understanding the
differences in the basic science of skin and hair is imperative in addressing
their unique needs. Despite the paucity of conclusive data on racial and ethnic
differences in skin of color, certain biologic differences do exist, which affect
the disease presentations of several cutaneous disorders in pigmented skin. While
the overall pathogenesis and treatments for acne in women of color are similar to
Caucasian men and women, individuals with darker skin types present more
frequently with dyschromias from acne, which can be difficult to manage. Melasma
is an acquired pigmentary disorder seen commonly in women with darker skin types
and is strongly associated with ultraviolet (UV) radiation, genetic factors, and
hormonal influences. Lastly, certain hair care practices and hairstyles are
unique among women of African descent, which may contribute to specific types of
hair loss seen in this population, such as traction alopecia, trichorrhexis
nodosa and central centrifugal cicatricial alopecia (CCCA).
PMID- 28492040
TI - What Ages Hair?
PMID- 28492041
TI - A ten-year comparison of women authorship in U.S. dermatology literature, 1999
vs. 2009.
AB - Women are entering medicine at increasing rates, particularly in dermatology. In
this study, we compared women's influence and status in academic dermatology with
that of men by examining authorship roles in peer-reviewed dermatology
literature. We examined the literature in 2009 and compared that to 10 years
prior (1999). A total of 1399 articles were reviewed, 594 of which met study
criteria and were included in statistical analysis. There was a marked increase
in senior female authorship over a decade (22% vs. 38%, p < 0.001). Female first
authorship increased as well (41% vs. 51%, p < 0.001). In contrast, changes in
male senior and first authorship were not statistically significant. Federal
funding for female senior authors increased over a decade (19% vs. 37%, p =
0.05), and female senior authors in the 2009 cohort were more likely to hold a
dual MD/PhD degree (0% vs. 11%, p = 0.04) or pure PhD degree (11% vs. 27%, p =
0.04). Women are approaching parity with men in terms of authorship in the
dermatology literature, and additional research training and attainment of
federal funding have helped women publish as senior authors.
PMID- 28492042
TI - Classifying discoid lupus erythematosus: background, gaps, and difficulties.
AB - To inform our ongoing efforts to develop defining features to be incorporated
into a novel set of classification criteria for discoid lupus erythematosus
(DLE), we conducted a literature review using the Ovid MEDLINE database. A search
was performed to identify studies reporting criteria used to distinguish DLE from
other cutaneous lupus erythematosus subtypes. We examined which clinical,
histopathologic, and serologic features have data to support their use as
effective features in distinguishing DLE from other potential disease mimickers
and cutaneous lupus subsets. Through our search, we were also able to identify
gaps that exist in the literature which can inform future directions for research
endeavors. We found that localization of lesions, characteristic features of
damage, and the absence of high titer Ro/SSA antibody seem most effective in
differentiating DLE from other cutaneous lupus erythematosus subtypes.
Histopathologic features and class of immunoreactant deposition appear to be less
helpful.
PMID- 28492043
TI - Considerations on biologic agents in psoriasis with the new pregnancy lactation
labeling rule.
PMID- 28492045
TI - Hair camouflage: A comprehensive review.
AB - Hair is venerated, cherished, and desired in societies throughout the world. Both
women and men express their individual identities through their hairstyles.
Healthy hair contributes to successful social assimilation, employment, and
overall quality of life. Therefore, hair loss can have detrimental effects on
almost every aspect of a person's life. In this review, we discuss the myriad of
options that aid in concealing and camouflaging hair loss to facilitate a
healthier-appearing scalp. Camouflage options for patients who suffer from hair
loss include full or partial wigs, hair extensions, concealing powders and
sprays, surgical tattoos, and hair transplants. We describe these modalities in
detail and discuss their respective advantages and disadvantages.
PMID- 28492046
TI - Introduction to women's health therapeutics in dermatology: Special edition of
the International Journal of Women's Dermatology.
PMID- 28492044
TI - Helen Ollendorff Curth: A dermatologist's lasting legacy.
PMID- 28492047
TI - The ethical arguments in support of open access journals.
PMID- 28492048
TI - A review of the safety of cosmetic procedures during pregnancy and lactation.
AB - The safety of cosmetic procedures in patients who are pregnant and/or lactating
is a complex clinical question surrounded by uncertainty. Our objective is to
consolidate data on the safety of commonly requested cosmetic procedures during
pregnancy and lactation after a systematic review of the current literature to
guide evidence-based care in the future. A systematic search of the PubMed
database was conducted for articles on cosmetic procedures during pregnancy and
lactation. Due to a lack of controlled trials, case reports and series were
considered. Minor procedures such as shave, punch, snipping, and electrocautery
are considered safe. With respect to chemical peels, glycolic and lactic acid
peels are deemed safe; however, trichloracetic and salicylic acid peels should be
avoided or used with caution. Although safety data on botulinum toxin A is
insufficient, the procedure may be safe because systemic absorption and placental
transfer are negligible. Sclerotherapy can be safe during pregnancy but must be
avoided during the first trimester and after week 36 of the pregnancy. Laser and
light therapies have been considered generally safe for patients with
granulomatous conditions and condylomata. Epilation should be limited to waxing,
shaving, and topical treatments instead of permanent procedures. In patients who
are lactating, most therapies discussed above are safe but fat transfer,
sclerotherapy, and tumescent liposuction are not recommended. Better evidence is
needed to make concrete recommendations on the safety of cosmetic therapy during
pregnancy and lactation but preliminary evidence suggests excellent safety
profiles for many commonly requested cosmetic procedures.
PMID- 28492049
TI - A review of laser and light therapy in melasma.
AB - Melasma is a dysregulation of the homeostatic mechanisms that control skin
pigmentation and excess pigment is produced. Traditional treatment approaches
with topical medications and chemical peels are commonly used but due to the
refractory and recurrent nature of melasma, patients often seek alternative
treatment strategies such as laser and light therapy. Several types of laser and
light therapy have been studied in the treatment of melasma. Intense pulsed
light, low fluence Q-switched lasers, and non-ablative fractionated lasers are
the most common lasers and light treatments that are currently performed. They
all appear effective but there is a high level of recurrence with time and some
techniques are associated with an increased risk for postinflammatory hyper- or
hypopigmentation. The number and frequency of treatments varies by device type
but overall, Q-switched lasers require the greatest number of treatment
applications to see a benefit. Vascular-specific lasers do not appear to be
effective for the treatment of melasma. Ablative fractionated lasers should be
used with caution because they have a very high risk for postinflammatory hypo-
and hyperpigmentation. The use of nonablative fractionated laser treatments
compared with other laser and light options may result in slightly longer
remission intervals. Picosecond lasers, fractional radiofrequency, and laser
assisted drug delivery are promising future approaches to treat melasma. The goal
of this review is to summarize the efficacy and safety of the most commonly used
laser and light therapies to treat melasma, briefly present future laser-based
treatment options for patients with melasma, and provide recommendations for
treatment on the basis of the reviewed information.
PMID- 28492050
TI - Update on biologic safety for patients with psoriasis during pregnancy.
AB - Biologic agents have become more common to treat patients with psoriasis, but
concerns about their effect on pregnancy and lactation often preclude this
treatment during these time periods. During the past decade, we have gained a
much better understanding of the course of psoriasis during pregnancy and the
safety of the use of biologic agents during pregnancy and lactation. Under
certain circumstances, biologic agents can be considered appropriate treatment
options for patients who are pregnant or lactating.
PMID- 28492051
TI - Prognosis for women diagnosed with melanoma during, before, or after pregnancy:
Weighing the evidence.
AB - Approximately one third of women who are diagnosed with malignant melanoma are of
childbearing age. Therefore, it is not surprising that some studies have found
malignant melanoma to be one of the most common malignancies diagnosed in
pregnant women. The impact of pregnancy-related hormonal changes on melanoma
development and progression remains controversial. Women undergo immunologic
changes during pregnancy that may decrease tumor surveillance. Additionally,
hormone receptors are found on some melanomas. Unfortunately, many of the past
and even recent studies that have been published and are reviewed herein did not
uniformly use appropriate control groups, account for confounding covariates, or
employ appropriate statistical analysis, which makes it difficult to rely on the
conclusions they reach. However, a review of the better controlled and
preponderant studies demonstrates that pregnancy-associated melanomas are not
associated with a poorer prognosis.
PMID- 28492052
TI - Dermatologic conditions in patients of color who are pregnant.
AB - Certain dermatoses that present during pregnancy have a predilection for
populations with skin of color (SOC). Additionally, certain systemic diseases
such as systemic lupus erythematosus tend to be more aggressive during pregnancy
and confer worse prognoses in women with SOC. The purpose of this review is to
highlight the unique implications of selected diseases during pregnancy as it
relates to SOC. Dermatologists should be vigilant for the unique clinical
variations of dermatological conditions in patients of color who are pregnant to
ensure correct diagnoses and optimize treatment outcomes.
PMID- 28492053
TI - Association of ethnicity, Fitzpatrick skin type, and hirsutism: A retrospective
cross-sectional study of women with polycystic ovarian syndrome.
AB - BACKGROUND: The complex interplay between ethnicity, Fitzpatrick skin type (FST),
and hirsutism in patients with polycystic ovarian syndrome (PCOS) is poorly
understood. OBJECTIVE: In this cross-sectional, retrospective analysis, we
examined the prevalence, severity, and distribution of hirsutism with clinician
rated site-specific and total modified Ferriman-Gallwey (mFG) visual scoring in a
diverse cohort of American patients with PCOS. METHODS: Independent analyses were
conducted on the basis of patient-reported FST ratings and ethnicity. RESULTS: In
this PCOS cohort, a correlation was found between hirsutism and ethnicity and the
highest prevalence of hirsutism and total mFG scores was observed in Hispanic,
Middle Eastern, African American, and South Asian patients. A positive
correlation between hirsutism and FST was also observed with an increasing
prevalence of hirsutism in the group of patients with higher FSTs. Significant
trends in the anatomic distribution of hirsutism were observed between ethnic
groups as well. A higher facial mFG score was found in African American patients
but higher mFG scores in the truncal and extremity regions were observed in
Middle Eastern patients. Truncal hirsutism was also associated with higher FSTs.
CONCLUSIONS: Ethnicity and FST may be important variables in both the
quantitative and qualitative presentations of hirsutism in women with PCOS and
should be considered in the diagnostic evaluation of any patient who is suspected
of having the condition. Previously published studies that examined ethnicity,
FST, and hirsutism in homogeneous cohorts limited comparison and generalizability
but the strength of this study lies in its detailed analysis within a single
large and diverse PCOS cohort. Validated studies are needed to determine whether
clinical criteria for hirsutism should be adjusted for ethnicity and FST in the
PCOS population and particularly within diverse cohorts and patients of mixed
ancestry.
PMID- 28492054
TI - A Review of hormone-based therapies to treat adult acne vulgaris in women.
AB - Hormone-based therapies including combined oral contraceptive medications and
spironolactone are considered effective therapies to treat adult acne in women.
Our objective is to provide a concise and comprehensive overview of the types of
hormonal therapy that are available to treat acne and comment on their efficacy
and safety profiles for clinical practice. A systematic search using the PubMed
Database was conducted to yield 36 relevant studies for inclusion in the review
and several conclusions were drawn from the literature. Treatment with oral
contraceptive pills leads to significant reductions in lesion counts across all
lesion types compared with placebo. There were no consistent differences in
efficacy between the different combined oral contraceptive formulations. In terms
of risk, oral contraceptive pill users had three-times increased odds of venous
thromboembolism versus non-users according to a recent meta-analysis (95%
confidence interval 2.46-2.59). Data on oral contraceptive pill use and breast
cancer risk are conflicting but individual patient risk factors and histories
should be discussed and considered when prescribing these medications. However,
use of these medications does confer measurable protection from endometrial and
ovarian cancer. Spironolactone was also shown to be an effective alternative
treatment with good tolerability. Combined oral contraceptive medications and
spironolactone as adjuvant and monotherapies are safe and effective to treat
women with adult acne. However, appropriate clinical examinations, screening, and
individual risk assessments particularly for venous thromboembolism risk must be
conducted prior to initiating therapy.
PMID- 28492055
TI - Hormonal therapy in female pattern hair loss.
PMID- 28492057
TI - Dermatologic care of the transgender patient.
AB - Given the complexities of the transitioning process, transgender individuals may
face unique dermatologic needs in addition to routine care. Exogenous hormones
affect hair and sebum production, gender-confirming surgeries often require
dermatologic pre- and postoperative interventions, and postoperative anatomy may
show unique presentations of routine skin conditions. Aesthetic techniques that
are often used for rejuvenation may have a role in facial feminization and
masculinization and unfortunately are too frequently performed by nonmedical
personnel with negative consequences. Ultimately, physicians should strive to
make their office a more accommodating environment for transgender individuals.
PMID- 28492056
TI - Lichenoid vulvar disease: A review.
AB - Vulvar dermatoses are common, potentially debilitating conditions that can be
seen by a variety of medical specialists. Lichenoid vulvar diseases, namely
lichen sclerosus (LS), lichen planus (LP), and lichen simplex chronicus (LSC),
can all negatively impact patients' quality of life and LS and LP also have an
association with squamous cell carcinoma. It is essential that dermatologists are
familiar with the unique features of each of these conditions to ensure the
appropriate management and follow up. Herein, we provide an update on the
epidemiology, clinical presentation, histopathology, and treatment of patients
with vulvar LS, LP, and LSC.
PMID- 28492058
TI - Sexism in medicine, circa 2016-2017.
PMID- 28492059
TI - Severity of memory impairment in the elderly: Association with health care
resource use and functional limitations in the United States.
AB - INTRODUCTION: Dementia is a prevalent condition in older adults associated with
decline in cognitive and functional abilities and substantial burden. This study
assessed the prevalence and impact of subjective memory impairment in the United
States. METHODS: The 2011 to 2014 National Health and Nutrition Examination
Survey, a population-based, nationally representative survey, was analyzed. Data
included medical examinations, self-reported cognitive and functional
limitations, and health care utilization over 1 year. Participants were aged >=65
years and completed both interview and medical examination components.
Descriptive analyses of patient characteristics were performed, and complex
survey regression models were used to test associations. RESULTS: Of 2431 survey
participants included, 53.1% had no memory impairment, 40.1% had early-stage
memory impairment, and 6.6% had late-stage memory impairment. In adjusted
analyses, late-stage versus no impairment was associated with more functional
limitations (odds ratio [OR] = 7.26, P < .001), greater health care utilization
(OR = 2.46, P < .001), and higher likelihood of seeing a mental health specialist
(OR = 3.06, P = .001). DISCUSSION: Consistent with previous research, individuals
with late-stage memory impairment had significantly greater functional
limitations and higher health care utilization versus individuals with early
stage or no memory impairment.
PMID- 28492060
TI - Subcutaneous Implants of a Cholesterol-Triglyceride-Buprenorphine Suspension in
Rats.
AB - A Target Animal Safety protocol was used to examine adverse events in male and
female Fischer F344/NTac rats treated with increasing doses of a subcutaneous
implant of a lipid suspension of buprenorphine. A single injection of 0.65 mg/kg
afforded clinically significant blood levels of drug for 3 days. Chemistry,
hematology, coagulation, and urinalysis values with 2- to 10-fold excess doses of
the drug-lipid suspension were within normal limits. Histopathology findings were
unremarkable. The skin and underlying tissue surrounding the drug injection were
unremarkable. Approximately 25% of a cohort of rats given the excess doses of
1.3, 3.9, and 6.5 mg/kg displayed nausea-related behavior consisting of
intermittent and limited excess grooming and self-gnawing. These results confirm
the safety of cholesterol-triglyceride carrier systems for subcutaneous drug
delivery of buprenorphine in laboratory animals and further demonstrate the
utility of lipid-based carriers as scaffolds for subcutaneous, long-acting drug
therapy.
PMID- 28492061
TI - Viability of Airborne Tumor Cells during Excision by Ultrasonic Device.
AB - Background. Laparoscopic surgery has become more widely used, but peritoneal
dissemination and port-site metastasis have been reported to occur in these
surgeries. One reason for these problems is the ultrasonically activated scalpel
(UAS) used for laparoscopic surgery. This study aimed to investigate the
viability of airborne cells released during cancer dissection using a UAS.
Methods. Flank tumors measuring about 2 cm were induced in male NOD-Cg
Rag1tm1MomIL2rgtm1wjl/SzJ mice by subcutaneous injection of 1 * 106 HepG2 cells.
Dissection was performed with UAS (in high or low power modes) and PowerStar
bipolar scissors. The mist of released tissue was collected in cell culture
medium. The viability of the cellular material was assessed with trypan blue
exclusion cell counting, counting after immunofluorescence staining, and flow
cytometric analysis. Results. Large quantities of cellular debris were trapped in
the tissue dispersed by both devices. In all experiments, there were
significantly more viable cells produced by the UAS in high power mode. By using
suction at the excision site, the number of viable cancer cells was reduced.
Conclusions. This study demonstrates that viable cancer cells can be released
into the nearby environment during tumor ablation with a UAS.
PMID- 28492062
TI - Intraoperative Injection of Technetium-99m Sulfur Colloid for Sentinel Lymph Node
Biopsy in Breast Cancer Patients: A Single Institution Experience.
AB - Background. Most institutions require a patient undergoing sentinel lymph node
biopsy to go through nuclear medicine prior to surgery to be injected with
radioisotope. This study describes the long-term results using intraoperative
injection of radioisotope. Methods. Since late 2002, all patients undergoing a
sentinel lymph node biopsy at the Yale-New Haven Breast Center underwent
intraoperative injection of technetium-99m sulfur colloid. Endpoints included
number of sentinel and nonsentinel lymph nodes obtained and number of positive
sentinel and nonsentinel lymph nodes. Results. At least one sentinel lymph node
was obtained in 2,333 out of 2,338 cases of sentinel node biopsy for an
identification rate of 99.8%. The median number of sentinel nodes found was 2 and
the mean was 2.33 (range: 1-15). There were 512 cases (21.9%) in which a sentinel
node was positive for metastatic carcinoma. Of the patients with a positive
sentinel lymph node who underwent axillary dissection, there were 242 cases
(54.2%) with no additional positive nonsentinel lymph nodes. Advantages of
intraoperative injection included increased comfort for the patient and
simplification of scheduling. There were no radiation related complications.
Conclusion. Intraoperative injection of technetium-99m sulfur colloid is
convenient, effective, safe, and comfortable for the patient.
PMID- 28492063
TI - Vaccination with Killed but Metabolically Active E. coli Over-expressing
Hemagglutinin Elicits Neutralizing Antibodies to H1N1 Swine Origin Influenza A
Virus.
AB - There is a need for a fast and simple method for vaccine production to keep up
with the pace of a rapidly spreading virus in the early phases of the influenza
pandemic. The use of whole viruses produced in chicken eggs or recombinant
antigens purified from various expression systems has presented considerable
challenges, especially with lengthy processing times. Here, we use the killed but
metabolically active (KBMA) Escherichia coli (E. coli) to harbor the
hemagglutinin (HA) of swine origin influenza A (H1N1) virus (S-OIV) San
Diego/01/09 (SD/H1N1-S-OIV). Intranasal vaccination of mice with KBMA E. coli
SD/H1N1-S-OIV HA without adding exogenous adjuvants provoked detectable
neutralizing antibodies against the virus-induced hemagglutination within three
weeks. Boosting vaccination enhanced the titers of neutralizing antibodies, which
can decrease viral infectivity in Madin-Darby canine kidney (MDCK) cells. The
antibodies were found to specifically neutralize the SD/H1N1-S-OIV-, but not
seasonal influenza viruses (H1N1 and H3N2), -induced hemagglutination. The use of
KBMA E. coli as an egg-free system to produce anti-influenza vaccines makes
unnecessary the rigorous purification of an antigen prior to immunization,
providing an alternative modality to combat influenza virus in future outbreaks.
PMID- 28492064
TI - Biophysical characterization and modeling of human Ecdysoneless (ECD) protein
supports a scaffolding function.
AB - The human homolog of Drosophila ecdysoneless protein (ECD) is a p53 binding
protein that stabilizes and enhances p53 functions. Homozygous deletion of mouse
Ecd is early embryonic lethal and Ecd deletion delays G1-S cell cycle
progression. Importantly, ECD directly interacts with the Rb tumor suppressor and
competes with the E2F transcription factor for binding to Rb. Further studies
demonstrated ECD is overexpressed in breast and pancreatic cancers and its
overexpression correlates with poor patient survival. ECD overexpression together
with Ras induces cellular transformation through upregulation of autophagy.
Recently we demonstrated that CK2 mediated phosphorylation of ECD and interaction
with R2TP complex are important for its cell cycle regulatory function.
Considering that ECD is a component of multiprotein complexes and its crystal
structure is unknown, we characterized ECD structure by circular dichroism
measurements and sequence analysis software. These analyses suggest that the
majority of ECD is composed of alpha-helices. Furthermore, small angle X-ray
scattering (SAXS) analysis showed that deletion fragments, ECD(1-432) and ECD(1
534), are both well-folded and reveals that the first 400 residues are globular
and the next 100 residues are in an extended cylindrical structure. Taking all
these results together, we speculate that ECD acts like a structural hub or
scaffolding protein in its association with its protein partners. In the future,
the hypothetical model presented here for ECD will need to be tested
experimentally.
PMID- 28492065
TI - Revisiting olfactory receptors as putative drivers of cancer.
AB - Background: Olfactory receptors (ORs) recognize odorant molecules and activate a
signal transduction pathway that ultimately leads to the perception of smell.
This process also modulates the apoptotic cycle of olfactory sensory neurons in
an olfactory receptor-specific manner. Recent reports indicate that some
olfactory receptors are expressed in tissues other than the olfactory epithelium
suggesting that they may have pleiotropic roles. Methods: We investigated the
expression of 301 olfactory receptor genes in a comprehensive panel of 968 cancer
cell lines. Results: Forty-nine per cent of cell lines show expression of at
least one olfactory receptor gene. Some receptors display a broad pattern of
expression across tumour types, while others were expressed in cell lines from a
particular tissue. Additionally, most of the cancer cell lines expressing
olfactory receptors express the effectors necessary for OR-mediated signal
transduction. Remarkably, among cancer cell lines, OR2C3 is exclusively expressed
in melanoma lines. We also confirmed the expression of OR2C3 in human melanomas,
but not in normal melanocytes. Conclusions: The pattern of OR2C3 expression is
suggestive of a functional role in the development and/or progression of
melanoma. Some olfactory receptors may contribute to tumorigenesis.
PMID- 28492067
TI - Social Structure and Depression in TrevorSpace.
AB - We discover patterns related to depression in the social graph of an online
community of approximately 20,000 lesbian, gay, and bisexual, transgender, and
questioning youth. With survey data on fewer than two hundred community members
and the network graph of the entire community (which is completely anonymous
except for the survey responses), we detected statistically significant
correlations between a number of graph properties and those TrevorSpace users
showing a higher likelihood of depression, according to the Patient Healthcare
Questionnaire-9, a standard instrument for estimating depression. Our results
suggest that those who are less depressed are more deeply integrated into the
social fabric of TrevorSpace than those who are more depressed. Our techniques
may apply to other hard-to-reach online communities, like gay men on Facebook,
where obtaining detailed information about individuals is difficult or expensive,
but obtaining the social graph is not.
PMID- 28492068
TI - Survival and Neurodevelopment of Periviable Infants.
PMID- 28492069
TI - Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery.
PMID- 28492070
TI - Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery.
PMID- 28492066
TI - Progression inference for somatic mutations in cancer.
AB - Computational methods were employed to determine progression inference of genomic
alterations in commonly occurring cancers. Using cross-sectional TCGA data, we
computed evolutionary trajectories involving selectivity relationships among
pairs of gene-specific genomic alterations such as somatic mutations, deletions,
amplifications, downregulation, and upregulation among the top 20 driver genes
associated with each cancer. Results indicate that the majority of hierarchies
involved TP53, PIK3CA, ERBB2, APC, KRAS, EGFR, IDH1, VHL, etc. Research into the
order and accumulation of genomic alterations among cancer driver genes will ever
increase as the costs of nextgen sequencing subside, and personalized/precision
medicine incorporates whole-genome scans into the diagnosis and treatment of
cancer.
PMID- 28492071
TI - Left Ventricular Assist Devices for Advanced Heart Failure.
PMID- 28492072
TI - Opioid Prescribing by Emergency Physicians and Risk of Long-Term Use.
PMID- 28492073
TI - Polyvalent and Thermosensitive DNA Nanoensembles for Cancer Cell Detection and
Manipulation.
AB - Development of smart DNA nanostructures is of great value in cancer studies.
Here, by integrating rolling circle amplification (RCA) into split aptamer
design, a novel strategy of polyvalent and thermosensitive DNA nanoensembles was
first proposed for cancer cell detection and manipulation. In this strategy, a
long nanosolo ssDNA with repeated Split-b and Poly T regions was generated
through RCA. Split-b supplied polyvalent binding sites while Poly T supported
signal output by hybridizing with fluorophore-labeled poly A. After addition of
Split-a, nanoensembles formed on the cell surface due to target-induced assembly
of Split-a/Split-b from the free state to the recognition structure, and on the
basis of the thermosensitivity of split aptamer, nanoensembles were controlled
reversibly by changing temperatures. As proof of concept, split ZY11 against SMMC
7721 cancer was used to construct nanoensembles. Compared with monovalent split
aptamer, nanoensembles were demonstrated to have a much stronger interaction with
target cells, thus realizing an ~2.8-time increase in signal-to-background ratio
(SBR). Moreover, nanoensembles extended the tolerance range of target binding
from 4 degrees C to room temperature and speeded recognition thus achieving
almost 50% binding in 1 min. Then, nanoensembles were successfully applied to
detect 7721 cells in serum and mixed cell samples. By utilizing microplate well
surface as the model, temperature-controlled catch/release of target cells was
also realized with nanoensembles, even under unfriendly conditions for monovalent
split aptamer. The RCA-mediated aptameric nanoensembles strategy not only solved
the problem of split aptamer in inefficient binding but also paved a brand new
way for developing polyvalent and intelligent nanomaterials.
PMID- 28492074
TI - Inhibiting Firefly Bioluminescence by Chalcones.
AB - Chalcone refers to an aromatic ketone and an enone that constitutes the central
core for various important biological compounds in drug discovery. Moreover, the
firefly luciferase (Fluc) as the bioluminescent reporter has been widely used in
life science research and high-throughput screening (HTS). However, Fluc might
suffer from direct inhibition by HTS compounds resulting in the occurrence of
"false positives." In the current research, we discovered a series of chalcone
compounds as Fluc inhibitors with favorable potency both in vitro and in vivo.
Moreover, our compound 3i showed remarkable systemic inhibition in transgenic
mice. Both enzymatic kinetics study and cocrystal structure demonstrated that
compound 3i is competitive for substrate aminoluciferin, while noncompetitive for
ATP. Besides, compound 3i exhibited excellent selectivity as a promising
quenching agent in a simulated dual-luciferase reporter assay. We believed that
our research would contribute to improving scientists' awareness of the Fluc
inhibitors, pay attention to the bias results, and even expand the utilization of
bioluminescence in life science research.
PMID- 28492075
TI - Energy Transfer Highway in Nd3+-Sensitized Nanoparticles for Efficient near
Infrared Bioimaging.
AB - Despite the large absorption cross-section of Nd3+ dopant as a sensitizer in
lanthanide doped luminescence system, the strong cross-relaxation effect of it
impedes the promotion of doping concentration and thus reduces the utilization of
excitation light. In this work, we introduce a highly efficient acceptor, Yb3+
ion, which can quickly receive energy from Nd3+ ions, to construct an energy
transfer highway for the enhancement of near-infrared emission. By using the
energy transfer highway, the doping amount of Nd3+ ions in our NaYF4:Yb,Nd@CaF2
core/shell nanoparticles (CSNPs) can be markedly elevated to 60%. The quantum
yield of CSNPs was determined to be 20.7%, which provides strong near-infrared
luminescence for further bioimaging application. Remarkably, deep tissue
penetration depth (~10 mm) in in vitro imaging and high spatial resolution of
blood vessel (~0.19 mm) in in vivo imaging were detected clearly with weak
autofluorescence, demonstrating that probes can be used as excellent NIR
biosensors.
PMID- 28492076
TI - Total Synthesis of gamma-Indomycinone and Kidamycinone by Means of Two
Regioselective Diels-Alder Reactions.
AB - An efficient access for the synthesis of pluramycinones is described. Total
syntheses of racemic gamma-indomycinone and kidamycinone were achieved by means
of two Diels-Alder reactions. A first Diels-Alder condensation followed by a
Stille cross-coupling is used for the elaboration of the desired substituted
dienes which will be involved in the second pericyclic reaction with juglone to
construct the tetracyclic core of pluramycinones.
PMID- 28492077
TI - Anomalously Rapid Tunneling: Charge Transport across Self-Assembled Monolayers of
Oligo(ethylene glycol).
AB - This paper describes charge transport by tunneling across self-assembled
monolayers (SAMs) of thiol-terminated derivatives of oligo(ethylene glycol)
(HS(CH2CH2O)nCH3; HS(EG)nCH3); these SAMs are positioned between gold bottom
electrodes and Ga2O3/EGaIn top electrodes. Comparison of the attenuation factor
(beta of the simplified Simmons equation) across these SAMs with the
corresponding value obtained with length-matched SAMs of oligophenyls (HS(Ph)nH)
and n-alkanethiols (HS(CH2)nH) demonstrates that SAMs of oligo(ethylene glycol)
have values of beta (beta(EG)n = 0.29 +/- 0.02 natom-1 and beta = 0.24 +/- 0.01 A
1) indistinguishable from values for SAMs of oligophenyls (beta(Ph)n = 0.28 +/-
0.03 A-1), and significantly lower than those of SAMs of n-alkanethiolates
(beta(CH2)n = 0.94 +/- 0.02 natom-1 and 0.77 +/- 0.03 A-1). There are two
possible origins for this low value of beta. The more probable involves hole
tunneling by superexchange, which rationalizes the weak dependence of the rate of
charge transport on the length of the molecules of HS(EG)nCH3 using interactions
among the high-energy, occupied orbitals associated with the lone-pair electrons
on oxygen. Based on this mechanism, SAMs of oligo(ethylene glycol)s are good
conductors (by hole tunneling) but good insulators (by electron and/or hole drift
conduction). This observation suggests SAMs derived from these or electronically
similar molecules are a new class of electronic materials. A second but less
probable mechanism for this unexpectedly low value of beta for SAMs of S(EG)nCH3
rests on the possibility of disorder in the SAM and a systematic discrepancy
between different estimates of the thickness of these SAMs.
PMID- 28492078
TI - General Strategy for Controlled Synthesis of NixPy/Carbon and Its Evaluation as a
Counter Electrode Material in Dye-Sensitized Solar Cells.
AB - Hydrothermal treatment of nickel acetate and phosphoric acid aqueous solution
followed with a carbothermal reduction assisted phosphorization process using
sucrose as the carbon source for the controlled synthesis of NixPy/C was
successfully realized for the first time. The critical synthesis factors,
including reduction temperature, phosphorus/nickel ratio, pH, and sucrose amount
were systematically investigated. Remarkably, the carbon serves as a reducer and
plays a determinative role in the transformation of Ni2P2O7 into Ni2P/C. The
synthesis strategy is divided into four distinguishable stages: (1) hydrothermal
preparation of Ni3(PO4)2.8H2O precursor for stabilizing P sources; (2)
dimerization of Ni3(PO4)2.8H2O into more thermal stable Ni2P2O7 amorphous phase
along with the generation of NiO; (3) carbothermal reduction and phosphidation of
NiO into NixPy (0 <= y/x <= 0.5); and (4) further phosphidation of mixed-phase
NixPy and carbothermal reduction of Ni2P2O7 into single-phase Ni2P. The resultant
Ni2P, the highly active phase in electrocatalysis, was applied as counter
electrode in a dye-sensitized solar cell (DSSC). The DSSC based on Ni2P with 10.4
wt.% carbon delivers a power conversion efficiency of 9.57%, superior to that of
state-of-the-art Pt-based cell (8.12%). The abundant Nidelta+ and Pdelta- active
sites and the metal-like conductivity account for its outstanding catalytic
performance.
PMID- 28492079
TI - Chemical Vapor Deposition Synthesis and Optical Properties of Nb2O5 Thin Films
with Hybrid Functional Theoretical Insight into the Band Structure and Band Gaps.
AB - Nb2O5 is an important material able to exist in many polymorphs with unique
optical properties and morphologies that are dependent on the synthetic route.
Here we report a novel ambient-pressure chemical vapor deposition route to Nb2O5
via aerosol-assisted chemical vapor deposition. The amorphous as-deposited films
were annealed in air to obtain the the three most stable crystal structures:
orthorhombic, tetragonal, and monoclinic. The films were thoroughly characterized
for their material properties, and an in-depth study into the optical properties
was carried out using state-of-the-art hybrid functional theory that allowed more
insight into the optical properties of the materials.
PMID- 28492080
TI - Artemisinin-Luminol Chemiluminescence for Forensic Bloodstain Detection Using a
Smart Phone as a Detector.
AB - Forensic luminol chemiluminescence test is one of the most sensitive and popular
methods for the determination of latent bloodstains. It mainly uses hydrogen
peroxide or sodium perborate as coreactants. The easy decomposition of hydrogen
peroxide and sodium perborate in the presence of many ions significantly affects
the selectivity. Artemisinin is a natural peroxide that is quite stable in the
presence of common ions. In the present study, artemisinin has been exploited for
the forensic bloodstain chemiluminescence detection for the first time. Using
smart phone as cost-effective portable detector, the visual detection of
bloodstains has been achieved with a dilution factor of blood up to 100 000.
Moreover, this system shows excellent selectivity against many common species. It
can well differentiate bloodstains from other stains, such as coffee, brown
sugar, and black tea. Both favorable sensitivity and selectivity makes the
present method promising in forensic detection.
PMID- 28492081
TI - Junction Propagation in Organometal Halide Perovskite-Polymer Composite Thin
Films.
AB - With the emergence of organometal halide perovskite semiconductors, it has been
discovered that a p-i-n junction can be formed in situ due to the migration of
ionic species in the perovskite when a bias is applied. In this work, we
investigated the junction formation dynamics in methylammonium lead tribromide
(MAPbBr3)/polymer composite thin films. It was concluded that the p- and n- doped
regions propagated into the intrinsic region with an increasing bias, leading to
a reduced intrinsic perovskite layer thickness and the formation of an effective
light-emitting junction regardless of perovskite layer thicknesses (300 nm to 30
MUm). The junction propagation also played a major role in deteriorating the LED
operation lifetime. Stable perovskite LEDs can be achieved by restricting the
junction propagation after its formation.
PMID- 28492082
TI - Metabolomics Approach in the Investigation of Metabolic Changes in Obese Men
after 24 Weeks of Combined Training.
AB - Obesity is associated with comorbidities related to metabolic disorders due to
excess of adipose tissue. Physical exercise has a major role in the prevention of
obesity. Combined training (CT), in particular, has been shown to improve markers
of health. In this study, we used 1H NMR-based metabolomics to investigate
changes in the metabolism of obese men after 24 weeks of CT. Twenty-two obese
(body mass index 31 +/- 1.4 kg/m2), middle-aged men (48.2 +/- 6.1 years) were
randomly assigned to a control group (CG, n = 11) or CT group (n = 11). The CT
was performed three times a week (resistance and aerobic training) for 24 weeks.
Blood samples were collected before and after experimental period. There was an
improvement in body composition and physical fitness indices after CT training.
Multivariate PCA and PLS-DA models showed a distinct separation between groups.
Twenty metabolites with importance for projection (VIP) >1.0 were identified, and
four were classified as best discriminators (tyrosine, 2-oxoisocaproate,
histidine, pyruvate). Some metabolites were correlated with strength, VO2 peak,
fat and lean body mass, waist circumference, and insulin. In conclusion, 24 weeks
of CT was effective for functional improvements and metabolic changes in obese
middle-aged men.
PMID- 28492083
TI - B(C6F5)3-Catalyzed Michael Reactions: Aromatic C-H as Nucleophiles.
AB - The Michael reaction is a widely used reaction for the C-C coupling of electron
poor olefins and C(sp3)-H pronucleophiles. Herein we report the Michael reaction
between alkenes and aromatic as well as heteroaromatic compounds as aromatic
C(sp2)-H nucleophiles under mild conditions. The reaction is catalyzed by readily
available Lewis acidic B(C6F5)3 and proceeds with high regioselectivity for a
wide substrate scope.
PMID- 28492084
TI - Prehospital triage of patients suffering severe dyspnoea using N-terminal pro
brain natriuretic peptide, the PreBNP trial: a randomised controlled clinical
trial.
AB - PURPOSE: The purpose of this study was to examine whether the addition of brain
natriuretic peptide measurement to the routine diagnostic work-up by prehospital
critical care team physicians improves triage in patients with severe dyspnoea.
METHODS: Prehospital critical care team physicians randomly assigned patients
older than 18 years with severe dyspnoea to routine diagnostic work-up or
diagnostic work-up with incorporated point-of-care N-terminal pro-brain
natriuretic peptide (NT-proBNP) measurement. The primary endpoint was the
proportion of patients with dyspnoea of primary cardiac origin triaged directly
to a department of cardiology. RESULTS: A total of 747 patients were randomly
assigned and 711 patients consented to participate, 350 were randomly assigned to
the NT-proBNP group and 361 to the routine work-up group. NT-proBNP was measured
in 90% (315/350) of patients in the NT-proBNP group and in 19% (70/361) of
patients in the routine work-up group. There was no difference in the proportion
of patients with dyspnoea of primary cardiac origin triaged directly to a
department of cardiology between the NT-proBNP group and the routine work-up
group (75% vs. 69%, P=0.22) in the intention-to-treat analysis. Sensitivity
analysis according to the de facto diagnostics performed showed results
consistent with this. No differences in hospital length of stay, intensive care
unit admission rates or mortality between the NT-proBNP group and the routine
work-up group were observed. CONCLUSION: Routine supplementary point-of-care
measurement of NT-proBNP in patients with severe dyspnoea did not improve triage
of patients with dyspnoea primarily caused by heart disease. ClinicalTrials.gov
identifier NCT02050282.
PMID- 28492085
TI - Self-managing HIV/AIDS: cultural competence and health among women in Nairobi,
Kenya.
AB - Despite recent efforts to supply antiretroviral therapy, many in Africa are not
receiving medication, instead relying on self-management in their attempts to
remain healthy. In Kenya, the majority of those infected are women who are below
the extreme poverty level. Building on research demonstrating a link between
knowledge of HIV/AIDS management and the length of time HIV-positive women have
lived in Nairobi, this article uses a cognitive anthropological approach that
conceives of culture as shared models and explores the relationship between how
well women know a cultural model of self-managing HIV/AIDS and health among women
who are not receiving biomedical treatment. Outcomes include reported perceived
stress, depressive symptoms, and recent illness episodes. Here, this association
of competence in the shared cultural model and health among women living in
extremely marginal economic conditions is explored from a biocultural perspective
to better understand this relationship. Knowledge of the model is a significant
predictor of better overall health even after controlling for age, education,
income, marital status, internal locus of control, and how long women have known
that they are HIV-positive. This article adds to the HIV/AIDS literature by
quantitatively linking health to cultural knowledge among an HIV-positive
population. It also contributes to the cultural consensus literature by
demonstrating health benefits of cultural knowledge.
PMID- 28492086
TI - Novel translational therapeutic strategy by sequencing primary liver cancer
genomes.
PMID- 28492087
TI - Sociodemographic characteristics associated with the use of effective and less
effective contraceptive methods: findings from the Understanding Fertility
Management in Contemporary Australia survey.
AB - OBJECTIVE: Unintended pregnancy and abortion may, in part, result from suboptimal
use of effective contraception. This study aimed to identify sociodemographic
factors associated with the use of effective and less effective methods among
women and men of reproductive age living in Australia. METHODS: In a cross
sectional national survey, 1544 women and men aged 18-51 were identified as being
at risk of pregnancy. Chi-square and logistic regression analyses were used to
assess the sociodemographic factors related to contraceptive use. RESULTS: Most
respondents (n = 1307, 84.7%) reported using a method of contraception. Use of
any contraceptive was associated with being born in Australia (Odds Ratio [OR]
1.89; 95% Confidence Interval [CI]1.186, 3.01; p = .008), having English as a
first language (OR 1.81; 95% CI: 1.07, 3.04; p = .026), having private health
insurance (OR 2.25; 95% CI 1.66, 3.04; p < .001), and not considering religion
important to fertility choices (OR 0.43; 95%CI 0.31, 0.60; p < .001). A third
used effective contraceptive methods (n = 534, 34.6%; permanent methods: 23.1%,
and long-acting reversible contraception (LARC): 11.4%). Permanent methods were
more likely to be used in rural areas (OR 0.62; 95%CI 0.46, 0.84; p = .002). Use
of the least effective, short-term methods was reported by nearly half (condoms:
25.6%, withdrawal: 12.5%, and fertility-awareness-based methods: 2.8%). Those who
relied on withdrawal were more likely to live in a metropolitan area (OR 2.85;
95% CI 1.95, 4.18; p < .001), and not have private health insurance (OR 0.52; 95%
CI 0.38, 0.71; p < .001). CONCLUSIONS: Targeted promotion of the broad range of
available contraceptives may raise awareness and uptake of more effective methods
and improve reproductive autonomy in certain population groups.
PMID- 28492088
TI - Donor selection for ex vivo-expanded natural killer cells as adoptive cancer
immunotherapy.
PMID- 28492089
TI - Does physical activity improve survival and mortality among patients with
different types of cancer?
PMID- 28492090
TI - Synthesis and structure-activity relationship of theasapogenol galactosides
against Magnaporthe oryzae.
AB - Camellia oleifera is expected to provide alternative aglycone to synthesize some
saponins similar to that from Schima superba with inhibitory activity against
Magnaporthe oryzae. Eight theasapogenol galactosides were synthesized via
protection of adjacent hydroxyl groups by a benzylidene for regioselective
glycosylation in the multi-hydroxyl sapogenin. Water soluble galactose chain
connected far from liposoluble end was a key group in inhibiting the growth of M.
oryzea unless theasapogenol was modified by two galactosyl groups or by one
galactosyl group and one benzylidene group. The amphoteric characteristics of
saponin such as saccharide group number, distance between bipolar groups play an
important role in inhibiting mycelium growth of M. oryzae.
PMID- 28492091
TI - The schizophrenia stigma and mass media: a search for news published by wide
circulation media in Brazil.
AB - Schizophrenia is the most common illness used today as a metaphor in the media
and routinely appears associated with crime and violence with no medical or
scientific rigor, reinforcing the stigma against this disorder. Evaluation of the
presence of structural stigma in the Brazilian media by means of a survey of
printed news and the Internet using the term schizophrenia and its correlates
under three aspects: (a) medical and scientific uses, (b) assigning a diagnosis
of schizophrenia to crime suspects with little or no medical or scientific rigor,
and (c) the metaphorical use. The study was conducted in three stages: search for
publications, classification of items found and analysis of the context in which
they were published. The survey was conducted in two periods: 2008 and 2011, the
first being restricted to the newspaper Folha de S. Paulo and the second extended
to the homepage of the main Brazilian print media. We found 229 texts,
distributed as follows: 89 (39%) records as science and health, with a tendency
to impersonality; 62 (27%) records as crime and violence, in which the
'diagnosis' of schizophrenia is given by lay people and 'supported' by an
archeology of the life of the suspect which enlists all sorts of non-standard
behavior; and 78 (34%) records of metaphorical use, always with a negative
meaning. Most of the texts found (a) does not give voice to people with
schizophrenia and their suffering, (b) trivializes the use of this psychiatric
illness out of context to describe contradictory or of dubious character
political and economic decisions, and
PMID- 28492092
TI - Use of descriptive and experiential information in decision making by young and
older adults.
AB - Age differences involving decision by description versus decision by experience
were examined using the same general task structure to facilitate comparisons
across decision types. Experiment 1 compared younger (19-43 years) and older (65
85 years) adults in four different experimental conditions involving a choice
between a low-risk, low-return bet versus a high-risk, high-return bet.
Experiment 2 compared young (18-27 years) to older (60-87 years) adults using
similar experimental conditions, but with decisions involving a risky versus a
certain option. Contrary to expectations, minimal differences were observed
between ages in either study. Higher levels of ability and numeracy were
associated with better performance and greater ability to benefit from
experience, but the impact of these factors was not moderated by age. The results
suggest that factors other than the simple distinction between decisions by
description versus experience are necessary to characterize the nature of age
effects in decision-making.
PMID- 28492094
TI - Bronchial Mucoepidermoid Carcinoma With the Classic MAML2 Gene Rearrangement in a
2-year-old Boy.
AB - Pulmonary mucoepidermoid carcinoma (PMEC) is rare. To date, primary PMEC has not
been reported in a child younger than 3 years of age. We report a case of a 2
year-old boy who presented with 3 episodes of wheezing, cough, and fever over a
period of 1 month. Radiologic findings were consistent with foreign body
aspiration with consequent bronchial obstruction. Bronchoscopy was performed and
attempts to retrieve the foreign body resulted in a biopsy of a fleshy lesion. By
histology, the lesion was an epithelial neoplasm comprising cells arranged in a
nested pattern. The neoplastic cells were round with round nuclei and
amphophilic, vacuolated cytoplasm. Our diagnosis was low-grade salivary gland
type carcinoma of the bronchus. The pneumonectomy specimen showed a well
circumscribed, polypoid intrabronchial mass measuring 2.1 cm in greatest
dimension. Histologic examination of the tumor showed an admixture of
intermediate cells which were predominant, a small number of mucus cells and rare
foci of squamous cells. The final diagnosis rendered was a low-grade
mucoepidermoid carcinoma of the bronchus. Accurate diagnosis of PMEC can be
challenging on limited biopsy material as seen in the case reported here. The use
of molecular studies such as MAML2 gene rearrangement may facilitate diagnosis in
difficult cases. Increased awareness of this entity and further molecular studies
are needed for a better understanding of the pathogenesis of PMEC. To date, the
reported age range for primary bronchial mucoepidermoid carcinoma is between 3
years and 78 years. This case represents the youngest patient reported in the
English literature.
PMID- 28492093
TI - Higher prevalence of cerebral white matter hyperintensities in homozygous APOE-E4
allele carriers aged 45-75: Results from the ALFA study.
AB - Cerebral white matter hyperintensities are believed the consequence of small
vessel disease and are associated with risk and progression of Alzheimer's
disease. The E4 allele of the APOE gene is the major factor accountable for
Alzheimer's disease heritability. However, the relationship between white matter
hyperintensities and APOE genotype in healthy subjects remains controversial. We
investigated the association between APOE-E4 and vascular risk factors with white
matter hyperintensities, and explored their interactions, in a cohort of
cognitively healthy adults (45-75 years). White matter hyperintensities were
assessed with the Fazekas Scale from magnetic resonance images (575 participants:
74 APOE-E4 homozygotes, 220 heterozygotes and 281 noncarriers) and classified
into normal (Fazekas < 2) and pathological (>=2). Stepwise logistic regression
was used to study the association between pathological Fazekas and APOE genotype
after correcting for cardiovascular and sociodemographic factors. APOE-E4
homozygotes, but not heterozygotes, bear a significantly higher risk (OR 3.432;
95% CI [1.297-9.082]; p = 0.013) of displaying pathological white matter
hyperintensities. As expected, aging, hypertension and cardiovascular and
dementia risk scales were also positively associated to pathological white matter
hyperintensities, but these did not modulate the effect of APOE-E4/E4. In
subjects at genetic risk of developing Alzheimer's disease, the control of
modifiable risk factors of white matter hyperintensities is of particular
relevance to reduce or delay dementia's onset.
PMID- 28492095
TI - ?
PMID- 28492096
TI - Physiological and self-reported disgust reactions to obesity.
AB - There is accumulating evidence that disgust plays an important role in prejudice
toward individuals with obesity, but that research is primarily based on self
reported emotions. In four studies, we examined whether participants displayed a
physiological marker of disgust (i.e. levator labii activity recorded using
facial electromyography) in response to images of obese individuals, and whether
these responses corresponded with their self-reported disgust to those images.
All four studies showed the predicted self-reported disgust response toward
images of obese individuals. Study 1 further showed that participants exhibited
more levator activity to images of obese individuals than to neutral images.
However, Studies 2-4 failed to provide any evidence that the targets' body size
affected levator responses. These findings suggest that disgust may operate at
multiple levels, and that the disgust response to images of obese individuals may
be more of a cognitive-conceptual one than a physiological one.
PMID- 28492097
TI - Optimal control of a social epidemic model with media coverage.
AB - A new social epidemic model to depict alcoholism with media coverage is proposed
in this paper. Some fundamental properties of the model including existence and
positivity as well as boundedness of equilibria are investigated. Stability of
all equilibria are studied. The existence of the optimal control pair and
mathematical expressions of optimal control are obtained by Pontryagin's maximum
principle. Numerical simulations are also performed to illustrate our results.
Our results show that media coverage is an effective measure to quit drinking.
PMID- 28492098
TI - L'evaluation d'impact sur la sante en Monteregie : un processus appuye sur le
courtage de connaissances.
AB - Le present article fait etat du modele de soutien a la prise de decision applique
a l'evaluation d'impact sur la sante (EIS) en Monteregie, au Canada. Pour
repondre a la volonte de soutenir l'elaboration de politiques et projets
municipaux favorables a la sante et fondes sur les donnees probantes, la
Direction de sante publique a mis en oeuvre une demarche d'EIS dont les
fondements pratiques s'inspirent des experiences internationales en matiere d'EIS
et dont les assises theoriques reposent sur le partage et le courtage de
connaissances. L'experience monteregienne demontre que la strategie de courtage
de connaissances appliquees a l'EIS encourage un partage respectueux des
responsabilites et roles de chacune des parties prenantes et favorise
l'utilisation des connaissances de sante publique dans la prise de decision
municipale. Le courtage des connaissances permet de prendre en compte les enjeux
locaux dans les analyses d'impact et dans les recommandations aux decideurs. En
conclusion, il s'avere que l'implication des decideurs municipaux a la recherche
de solutions favorables a la sante permet d'inscrire les donnees probantes a
l'interieur des processus decisionnels et d'observer leur utilisation a plusieurs
niveaux. L'evaluation des premieres experiences d'EIS revele en effet que les
connaissances partagees repondent a des besoins immediats engendrant leur
utilisation directe, contribuent a des changements de perception et de pratique a
plus large echelle et font de la sante une valeur reconnue par les decideurs
publics et promue aupres de leurs citoyens pour accroitre l'acceptabilite des
initiatives municipales.
PMID- 28492099
TI - 'Let the stars shine in peace!' Niels Bohr and stellar energy, 1929-1934.
AB - Faced with various anomalies related to nuclear physics in particular, in 1929
Niels Bohr suggested that energy might not be conserved in the atomic nucleus and
the processes involving it. By this radical proposal he hoped not only to get rid
of the anomalies but also saw a possibility to explain a puzzle in astrophysics,
namely the energy generated by stars. Bohr repeated his suggestion of stellar
energy arising ex nihilo on several occasions but without ever going into detail.
In fact, it is not very clear what he meant or how seriously he took the stellar
energy hypothesis. This paper relates Bohr's comments to the period's attempts to
find a mechanism for stellar energy and also to the role played by astrophysics
at the Copenhagen institute. Moreover, it looks at how Bohr's hypothesis was
received not only by physicists but also by astronomers. In this regard the
disciplinary status of astrophysics and its contemporary relation to the new
quantum mechanics is of relevance. It turns out that, with very few exceptions,
the hypothesis was met with silence by astronomers and astrophysicists concerned
with the problem of stellar energy production. And yet, for a brief period of
time it did have an impact on how physicists thought about the interior of the
stars.
PMID- 28492100
TI - Data mining in road crash analysis: the context of developing countries.
AB - The recent advancements in the field of data mining have made vast progress in
extracting new information and hidden patterns from large datasets which are
often overlooked by the traditional statistical approaches. These methods focus
on searching for new and interesting hypothesis which were previously unobserved.
Road safety researchers working with the crash data from developed world have
seen encouraging success in obtaining new insight into crash mechanism through
data mining. An attempt was made in this study to apply these advance methods and
evaluate their performance in manifesting crash causes for Bangladesh. The study
applies hierarchical clustering to identify hazardous clusters, random forest to
find important variables explaining each of these clusters, and classification
and regression trees to unveil their respective crash mechanisms for the road
crash data of Bangladesh. The results identified several new interesting
relationships and acknowledged issues related to quality of data.
PMID- 28492101
TI - Evaluation of 2016 MAGNIMS MRI criteria for dissemination in space in patients
with a clinically isolated syndrome.
AB - OBJECTIVES: We compared validity of 2010 McDonald and newly proposed 2016
Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) criteria for
dissemination in space (DIS) in predicting the conversion to clinically definite
multiple sclerosis (CDMS) in patients with clinically isolated syndrome (CIS).
METHODS: Between 2006 and 2016, we enrolled 170 patients who had a first clinical
event suggestive of multiple sclerosis (MS) from seven referral hospitals in
Korea. Patients were classified into two groups based on the main outcome at the
last follow-up: CDMS converters, who experienced a second attack, and non
converters. RESULTS: Of 170 patients with mean follow-up duration of 54 months,
51% converted to CDMS. The sensitivity, specificity, accuracy, and positive and
negative predictive values of 2010 McDonald criteria were 70.9%, 63.1%, 67.1%,
66.3%, and 67.9%, and those for 2016 MAGNIMS criteria were 88.4%, 46.4%, 67.7%,
62.8%, and 79.6%, respectively. When we excluded 80 patients who underwent
disease-modifying therapy before the second clinical event, the specificity
increased to 92.3% and 84.6%, but the sensitivity decreased to 58.8% and 82.4%
for 2010 McDonald and 2016 MAGNIMS criteria, respectively. CONCLUSION: 2016
MAGNIMS magnetic resonance imaging (MRI) criteria for DIS showed higher
sensitivity but lower specificity than 2010 McDonald criteria in predicting
conversion to CDMS in CIS patients.
PMID- 28492102
TI - Determinants of fluid intelligence in healthy aging: Omega-3 polyunsaturated
fatty acid status and frontoparietal cortex structure.
AB - INTRODUCTION: Accumulating evidence indicates that cognitive decline depends not
only upon changes in brain health, but critically, also upon nutritional status.
Decline in fluid intelligence, one of the most debilitating aspects of cognitive
aging, has been linked to omega-3 polyunsaturated fatty acid (PUFA) status;
however, it is not known whether this phenomenon results from specific omega-3
PUFAs acting on particular aspects of brain health. Therefore, this study aims to
explore whether particular patterns of omega-3 PUFAs influence fluid intelligence
by supporting specific neural structures. METHODS: We measured six plasma
phospholipid omega-3 PUFAs, fluid intelligence, and regional gray matter volume
in the frontal and parietal cortices in 100 cognitively intact older adults (65
75 years old). A four-step mediation analysis was implemented using principal
component analysis and multivariate linear regressions, adjusted for age, gender,
education, and body mass index. RESULTS: The mediation analysis revealed that one
pattern of omega-3 PUFAs, consisting of alpha-linolenic acid, stearidonic acid,
and eicosatrienoic acid, was linked to fluid intelligence, and that total gray
matter volume of the left frontoparietal cortex (FPC) fully mediated the
relationship between this omega-3 PUFA pattern and fluid intelligence.
DISCUSSION: These data demonstrate that fluid intelligence may be optimally
supported by specific omega-3 PUFAs through preservation of FPC gray matter
structure in cognitively intact older adults. This report provides novel evidence
for the benefits of particular omega-3 PUFA patterns on fluid intelligence and
underlying gray matter structure.
PMID- 28492103
TI - Amphipathic secondary structure elements and putative cholesterol recognizing
amino acid consensus (CRAC) motifs as governing factors of highly specific matrix
protein interactions with raft-type membranes in enveloped viruses.
PMID- 28492104
TI - Oxytocin and Vasopressin: Powerful Regulators of Social Behavior.
AB - For many, the terms oxytocin and vasopressin immediately evoke images of animals
interacting with one another, as both of these neuropeptides have been implicated
as being part of the neurochemical "glue" that socially binds animals. However,
social environments and social interactions are complex and include behaviors
that bring animals together as well as behaviors that keep animals apart. It is
at the intersection of social context, social experience, and an individual's sex
that oxytocin and vasopressin act to modulate social behavior and social
cognition. In this review, this complexity will be explored across mammalian
species, with a focus on social memory, cooperative behaviors, and competitive
behaviors. Implications for humans as well as future directions will also be
considered.
PMID- 28492105
TI - Metastatic spinal cord compression as the first sign of malignancy.
AB - Background and purpose - Metastatic spinal cord compression (MSCC) as the initial
manifestation of malignancy (IMM) limits the time for diagnostic workup; most
often, treatment is required before the final primary tumor diagnosis. We
evaluated neurological outcome, complications, survival, and the manner of
diagnosing the primary tumor in patients who were operated for MSCC as the IMM.
Patients and methods - Records of 69 consecutive patients (51 men) who underwent
surgery for MSCC as the IMM were reviewed. The patients had no history of cancer
when they presented with pain (n = 2) and/or neurological symptoms (n = 67).
Results - The primary tumor was identified in 59 patients. In 10 patients, no
specific diagnosis could be established, and they were therefore defined as
having cancer of unknown primary tumor (CUP). At the end of the study, 16
patients were still alive (median follow-up 2.5 years). The overall survival time
was 20 months. Patients with CUP had the shortest survival (3.5 months) whereas
patients with prostate cancer (6 years) and myeloma (5 years) had the longest
survival. 20 of the 39 patients who were non-ambulatory preoperatively regained
walking ability, and 29 of the 30 ambulatory patients preoperatively retained
their walking ability 1 month postoperatively. 15 of the 69 patients suffered
from a total of 20 complications within 1 month postoperatively. Interpretation -
Postoperative survival with MSCC as the IMM depends on the type of primary tumor.
Surgery in these patients maintains and improves ambulatory function.
PMID- 28492107
TI - Aborted Tracheo-esophageal Fistula in a Neonate.
AB - Esophageal atresia (EA) is an uncommon congenital anomaly which is often
associated with a tracheoesophageal fistula. An isolated EA is a rarer anomaly
and its diagnosis has implications for the ongoing treatment and outcome of the
infant. For the first time, we report a case of a premature newborn with a pure
EA and a tracheal diverticulum, containing both respiratory and esophageal
mucosa. We have termed this an aborted trachea-esophageal fistula. Recognition of
these very rare variations of foregut anomalies may contribute to our
understanding of their pathogenesis.
PMID- 28492106
TI - Higher risk of revision for infection using systemic clindamycin prophylaxis than
with cloxacillin.
AB - Background and purpose - Clindamycin has not been compared with other antibiotics
for prophylaxis in arthroplasty. Since 2009, the Swedish Knee Arthroplasty
Register (SKAR) has been collecting information on the prophylactic antibiotic
regime used at every individual operation. In Sweden, when there is allergy to
penicillin, clindamycin has been the recommended alternative. We examined whether
there were differences in the rate of revision due to infection depending on
which antibiotic was used as systemic prophylaxis. Patients and methods -
Patients who had a total knee arthroplasty (TKA) performed due to osteoarthritis
(OA) during the years 2009-2015 were included in the study. Information on which
antibiotic was used was available for 80,018 operations (55,530 patients).
Survival statistics were used to calculate the rate of revision due to infection
until the end of 2015, comparing the group of patients who received cloxacillin
with those who received clindamycin as systemic prophylaxis. Results -
Cloxacillin was used in 90% of the cases, clindamycin in 7%, and cephalosporins
in 2%. The risk of being revised due to infection was higher when clindamycin was
used than when cloxacillin was used (RR =1.5, 95% CI: 1.2-2.0; p = 0.001). There
was no significant difference in the revision rate for other causes (p = 0.2).
Interpretation - We advise that patients reporting allergic reaction to
penicillin should have their allergic history explored. In the absence of a clear
history of type-I allergic reaction (e.g. urticaria, anaphylaxis, or
bronchospasm), we suggest the use of a third-generation cephalosporin instead of
clindamycin as perioperative prophylaxis when undergoing a TKR. No recommendation
can be given regarding patients with type-1 allergy.
PMID- 28492108
TI - Three-dimensional Simulation of Quantitative Ultrasound in Cancellous Bone Using
the Echographic Response of a Metallic Pin.
AB - Degenerative discopathy is a common pathology that may require spine surgery. A
metallic cylindrical pin is inserted into the vertebral body to maintain soft
tissues and may be used as a reflector of ultrasonic wave to estimate bone
density. The first aim of this paper is to validate a three-dimensional (3-D)
model to simulate the ultrasonic propagation in a trabecular bone sample in which
a metallic pin has been inserted. We also aim at determining the effect of
changes of bone volume fraction (BV/TV) and of positioning errors on the
quantitative ultrasound (QUS) parameters in this specific configuration. The
approach consists in coupling finite-difference time-domain simulation with X-ray
microcomputed tomography. The correlation coefficient between experimental and
simulated speed of sound (SOS)-respectively, broadband ultrasonic attenuation
(BUA)-was equal to 0.90 (respectively, 0.55). The results show a significant
correlation of SOS with BV/TV ( R = 0.82), while BUA values exhibit a nonlinear
behavior versus BV/TV. The orientation of the pin should be controlled with an
accuracy of around 1 degrees to obtain accurate results. The results indicate
that using the ultrasonic wave reflected by a pin has a potential to estimate the
bone density. SOS is more reliable than BUA due to its lower sensitivity to the
tilt angle.
PMID- 28492109
TI - Revisiting the role of dissimilarity of host communities in driving dissimilarity
of ectoparasite assemblages: non-linear vs linear approach.
AB - We revisited the role of dissimilarity of host assemblages in shaping
dissimilarity of flea assemblages using a non-linear approach. Generalized
dissimilarity models (GDMs) were applied using data from regional surveys of
fleas parasitic on small mammals in four biogeographical realms. We compared (1)
model fit, (2) the relative effects of host compositional and phylogenetic
turnover and geographic distance on flea compositional and phylogenetic turnover,
and (3) the rate of flea turnover along gradients of host turnover and geographic
distance with those from earlier application of a linear approach. GDMs
outperformed linear models in explaining variation in flea species turnover and
host dissimilarity was the best predictor of flea dissimilarity, irrespective of
scale. The shape of the relationships between flea compositional turnovers along
host compositional turnover was similar in all realms, whereas turnover along
geographic distance differed among realms. In contrast, the rate of flea
phylogenetic turnover along gradients of host phylogenetic turnover differed
among realms, whereas flea phylogenetic turnover did not depend on geographic
distance in any realm. We demonstrated that a non-linear approach (a) explained
spatial variation in parasite community composition better than and (b) revealed
patterns that were obscured by earlier linear analyses.
PMID- 28492110
TI - Characteristics of influential peers in the eyes of secondary school students: a
mixed method study.
AB - : Aim It is the aim of this study to explore the characteristics of influential
peers identified by schoolmates, and the mechanism by which they exert their
influence on their peers. BACKGROUND: Adolescent crowds are a salient influence
on the health-risk behaviors of peers, contributing to adolescent substance use
such as drinking alcohol, smoking cigarettes, and taking drugs. METHODS: A mixed
method study. Three schools granted us access to students and those who had been
nominated as influential by their peers. The students were asked to nominate and
indicated the characteristics of peers whom they considered influential in a
quantitative study. Those peers whom they considered influential were invited to
take part in focus group interviews. A total of six focus group interviews were
conducted, comprised of two groups from each school, with an average of seven
participants in each group. Findings Students considered caring and friendliness
(91.0%), being a buddy (88.5%), and entertaining/humor (86.8%) as the top three
characteristics of influential peers. The interviews revealed that the students
believed that they are influential because of their cheerfulness and humor,
considerateness, ability to communicate, popularity and sociability, sincerity
and trustworthiness, and because they possess the characteristics of a leader.
They also believed that their power to influence came about through their
helpfulness, accommodation, and the closeness of their relationships. Their
influence was manifested in both positive and negative ways on the academic
pursuits and health-risk behaviors of their peers. In order to engage at-risk
students in health promotion programs, it is important to identify their
influential peers, and to understand how adolescent friends may help one another
to resist behaviors that pose a risk to their health.
PMID- 28492111
TI - A comparison of disease susceptibility and innate immune response between diploid
and triploid Atlantic salmon (Salmo salar) siblings following experimental
infection with Neoparamoeba perurans, causative agent of amoebic gill disease.
AB - Few studies have focussed on the health and immunity of triploid Atlantic salmon
and therefore much is still unknown about their response to commercially
significant pathogens. This is important if triploid stocks are to be considered
for full-scale commercial production. This study aimed to investigate and compare
the response of triploid and diploid Atlantic salmon to an experimental challenge
with Neoparamoeba perurans, causative agent of amoebic gill disease (AGD). This
disease is economically significant for the aquaculture industry. The results
indicated that ploidy had no significant effect on gross gill score or gill
filaments affected, while infection and time had significant effects. Ploidy,
infection and time did not affect complement or anti-protease activities. Ploidy
had a significant effect on lysozyme activity at 21 days post-infection (while
infection and time did not), although activity was within the ranges previously
recorded for salmonids. Stock did not significantly affect any of the parameters
measured. Based on the study results, it can be suggested that ploidy does not
affect the manifestation or severity of AGD pathology or the serum innate immune
response. Additionally, the serum immune response of diploid and triploid
Atlantic salmon may not be significantly affected by amoebic gill disease.
PMID- 28492112
TI - Undergraduate antibiotic stewardship training: Are we leaving our future
prescribers 'flapping in the wind'?
PMID- 28492113
TI - Health research and safeguards: The South African journey.
AB - Health research, as a social good, needs to be conducted in the interests of the
common good. Because of the unfortunate exploitation of research participants
globally, safeguards for protections are necessary. Most international codes and
guidelines originated as responses to the abuse and mistreatment of research
subjects. By the 1890s, antivivisectionists were already calling for laws to
protect children, as a result of the increasing numbers of institutionalised
children being subjected to vaccine experiments in Europe and the USA. Just after
the turn of the century, the first attempt to test a polio vaccine was thwarted
after the American Public Health Association condemned the programme. In South
Africa, medical scientists were busy with discoveries and innovations as far back
as the 1800s. In December 1967, the historic first human heart transplant was
undertaken in Cape Town. Although it is unclear how much research preceded this
procedure, there is no doubt that the operation was done in a research setting,
and it had a far-reaching impact.
PMID- 28492114
TI - Assisted suicide and assisted voluntary euthanasia: Stransham-Ford High Court
case overruled by the Appeal Court - but the door is left open.
AB - Whether persons wishing to have doctor-assisted suicide or voluntary active
euthanasia may make a court application based on their rights in the Constitution
has not been answered by the Appeal Court. Therefore, if Parliament does not
intervene beforehand, such applications can be made - provided the applicants
have legal standing, full arguments are presented regarding local and foreign
law, and the application evidence is comprehensive and accurate. The Appeal Court
indicated that the question should be answered by Parliament because 'issues
engaging profound moral questions beyond the remit of judges to determine, should
be decided by the representatives of the people of the country as a whole'.
However, the Government has not implemented any recommendations on doctor
assisted suicide and voluntary active euthanasia made by the South African Law
Commission 20 years ago. The courts may still develop the law on doctor-assisted
death, which may take into account developments in medical practice. Furthermore,
'the possibility of a special defence for medical practitioners or carers would
arise and have to be explored'.
PMID- 28492115
TI - Human dignity and the future of the voluntary active euthanasia debate in South
Africa.
AB - The issue of voluntary active euthanasia was thrust into the public policy arena
by the Stransham-Ford lawsuit. The High Court legalised voluntary active
euthanasia - however, ostensibly only in the specific case of Mr Stransham-Ford.
The Supreme Court of Appeal overturned the High Court judgment on technical
grounds, not on the merits. This means that in future the courts can be
approached again to consider the legalisation of voluntary active euthanasia. As
such, Stransham-Ford presents a learning opportunity for both sides of the
legalisation divide. In particular, conceptual errors pertaining to human dignity
were made in Stransham-Ford, and can be avoided in future. In this article, I
identify these errors and propose the following three corrective principles to
inform future debate on the subject: (i) human dignity is violable; (ii) human
suffering violates human dignity; and (iii) the 'natural' causes of suffering due
to terminal illness do not exclude the application of human dignity.
PMID- 28492116
TI - Ethical and legal perspectives on the medical practitioners use of social media.
AB - Use of social media has increased exponentially throughout the world. Social
media provides a platform for building social and professional relationships that
can be used by all, including healthcare professionals. Alongside the benefits of
creating networks and spreading information wider and faster than is possible
with traditional communication channels, however, it presents ethical and legal
challenges. For health professionals, it poses a threat to confidentiality and
privacy owed to patients, colleagues and employers. It is vital for health
professionals to acknowledge that the same ethical and legal standards apply both
online and offline, and that they are accountable to professional bodies and the
law for their online activities. This article seeks to explore the ethical and
legal pitfalls facing health professionals using social media platforms.
Importantly, it seeks to create awareness about the cyberpsychology phenomenon
called the 'online disinhibition effect', responsible for lowering restraint
during online activities.
PMID- 28492117
TI - Biobanks in South Africa: A global perspective on privacy and confidentiality.
AB - The Universal Declaration of Bioethics and Human Rights (UDBHR) of the United
Nations Educational, Scientific and Cultural Organization (UNESCO) was adopted
unanimously in 2005 by the world community as a universal guideline, according to
which members of the global community were accountable to each other. Research
results from UNESCO show that the UDBHR has had little or no impact in South
Africa (SA). The primary objective of this article is to promote awareness of the
UDBHR in SA and Africa by focusing on Article 9 of the Declaration, which accepts
the right to privacy and confidentiality. For this objective to be relevant in
the SA context, depends on whether the guidelines of the National Department of
Health's Ethics in Health Research: Principles, Processes and Structures of 2015
acknowledge biobanks of the universally accepted ethical guidelines on privacy
and confidentiality of autonomous persons and whether these guidelines are
broadly in accordance with global bioethical guidelines.
PMID- 28492118
TI - Legal liability for failure to prevent pregnancy (wrongful pregnancy).
AB - Can the conception of a child ever constitute damage recoverable in law? This
article considers the liability of healthcare practitioners for failing to
prevent a pregnancy. Developments leading to the recognition of wrongful
pregnancy as a cause of (legal) action in South Africa (SA), are briefly
outlined. The salient points of the relevant judgments by SA courts are set out
to expose the rationale underlying the judgments and to highlight that
recognition of liability for wrongful pregnancy resulted from an application of
fair and equitable principles of general application. Conduct that could expose
practitioners to liability is identified from reported cases and inferred from
general principles laid down in case law.
PMID- 28492119
TI - Paraquat poisoning: Acute lung injury - a missed diagnosis.
AB - Paraquat is a herbicide of great toxicological importance because it is
associated with high mortality rates, mainly due to respiratory failure. We
report the case of a 28-year-old man admitted to the casualty department at
Ngwelezana Hospital, Empangeni, KwaZulu-Natal, South Africa, with a history of
vomiting and abdominal pain after ingestion of ~100 mL of an unknown substance,
later identified as paraquat, together with an unknown amount of alcohol, in a
suicide attempt. He developed respiratory distress associated with lung
parenchymal infiltrates that required ventilatory support and later a spontaneous
pneumothorax, and died in the intensive care unit. We discuss the importance of a
high index of suspicion of paraquat poisoning in rural areas, where paraquat is
readily available as a herbicide on farms, in patients with a similar
presentation. We further stress the importance of identifying the classic
radiological progression after paraquat poisoning, to help avoid a delay in
diagnosis if the culprit substance is not known (as happened in our case).
Lastly, we look at the importance of avoiding oxygen supplementation, and early
administration of immunosuppressive therapy, to improve outcome.
PMID- 28492120
TI - A rare case of massive hepatosplenomegaly due to acute lymphoblastic leukemia in
pregnancy.
AB - Acute lymphoblastic leukaemia (ALL) is rarely seen in pregnancy. Massive
hepatosplenomegaly as a presentation of ALL has not been described previously in
any patient population. A 30-year-old pregnant woman presented at 16 weeks'
gestation with epistaxis, jaundice, diffuse abdominal pain and distension,
massive hepatosplenomegaly and peripheral oedema. On the basis of blood tests,
bone marrow biopsy and imaging, a diagnosis of ALL complicated by massive
hepatosplenomegaly with splenic infarctions was made. The patient was referred to
oncology for appropriate chemotherapy.
PMID- 28492121
TI - South African medical students' perceptions and knowledge about antibiotic
resistance and appropriate prescribing: Are we providing adequate training to
future prescribers?
AB - BACKGROUND: Education of medical students has been identified by the World Health
Organization as an important aspect of antibiotic resistance (ABR) containment.
Surveys from high-income countries consistently reveal that medical students
recognise the importance of antibiotic prescribing knowledge, but feel
inadequately prepared and require more education on how to make antibiotic
choices. The attitudes and knowledge of South African (SA) medical students
regarding ABR and antibiotic prescribing have never been evaluated. OBJECTIVE: To
evaluate SA medical students' perceptions, attitudes and knowledge about
antibiotic use and resistance, and the perceived quality of education relating to
antibiotics and infection. METHODS: This was a cross-sectional survey of final
year students at three medical schools, using a 26-item self-administered
questionnaire. The questionnaires recorded basic demographic information,
perceptions about antibiotic use and ABR, sources, quality, and usefulness of
current education about antibiotic use, and questions to evaluate knowledge. Hard
copy surveys were administered during whole-class lectures. RESULTS: A total of
289 of 567 (51%) students completed the survey. Ninety-two percent agreed that
antibiotics are overused and 87% agreed that resistance is a significant problem
in SA - higher proportions than those who thought that antibiotic overuse (63%)
and resistance (61%) are problems in the hospitals where they had worked
(p<0.001). Most reported that they would appreciate more education on appropriate
use of antibiotics (95%). Only 33% felt confident to prescribe antibiotics, with
similar proportions across institutions. Overall, prescribing confidence was
associated with the use of antibiotic prescribing guidelines (p=0.003),
familiarity with antibiotic stewardship (p=0.012), and more frequent contact with
infectious diseases specialists (p<0.001). There was an overall mean correct
score of 50% on the knowledge questionnaire, with significant differences between
institutions. Students who used antibiotic prescribing guidelines and found their
education more useful scored higher on knowledge questionnaires. CONCLUSION:
There are low levels of confidence with regard to antibiotic prescribing among
final-year medical students in SA, and most students would like more education in
this area. Perceptions that ABR is less of a problem in their local setting may
contribute to inappropriate prescribing behaviours. Differences exist between
medical schools in knowledge about antibiotic use, with suboptimal scores across
institutions. The introduction and use of antibiotic prescribing guidelines and
greater contact with specialists in antibiotic prescribing may improve
prescribing behaviours.
PMID- 28492122
TI - Critical care admission of South African (SA) surgical patients: Results of the
SA Surgical Outcomes Study.
AB - BACKGROUND: Appropriate critical care admissions are an important component of
surgical care. However, there are few data describing postoperative critical care
admission in resource-limited low- and middle-income countries. OBJECTIVE: To
describe the demographics, organ failures, organ support and outcomes of non
cardiac surgical patients admitted to critical care units in South Africa (SA).
METHODS: The SA Surgical Outcomes Study (SASOS) was a 7-day national,
multicentre, prospective, observational cohort study of all patients >=16 years
of age undergoing inpatient non-cardiac surgery between 19 and 26 May 2014 at 50
government-funded hospitals. All patients admitted to critical care units during
this study were included for analysis. RESULTS: Of the 3 927 SASOS patients, 255
(6.5%) were admitted to critical care units; of these admissions, 144 (56.5%)
were planned, and 111 (43.5%) unplanned. The incidence of confirmed or strongly
suspected infection at the time of admission was 35.4%, with a significantly
higher incidence in unplanned admissions (49.1 v. 24.8%, p<0.001). Unplanned
admission cases were more frequently hypovolaemic, had septic shock, and required
significantly more inotropic, ventilatory and renal support in the first 48 hours
after admission. Overall mortality was 22.4%, with unplanned admissions having a
significantly longer critical care length of stay and overall mortality (33.3 v.
13.9%, p<0.001). CONCLUSION: The outcome of patients admitted to public sector
critical care units in SA is strongly associated with unplanned admissions.
Adequate 'high care-dependency units' for postoperative care of elective surgical
patients could potentially decrease the burden on critical care resources in SA
by 23%. This study was registered on ClinicalTrials.gov (NCT02141867).
PMID- 28492123
TI - Factors associated with contracting malaria in Ward 29 of Shamva District,
Zimbabwe, 2014.
AB - BACKGROUND: Malaria cases at Wadzanayi Clinic in Shamva District, Zimbabwe,
increased drastically, surpassing the epidemic threshold, in week four of
December 2013. This rise was sustained, which necessitated an investigation of
the outbreak. OBJECTIVES: To identify risk factors and system weaknesses to
improve epidemic preparedness and response. METHODS: An unmatched 1:1 case
control study was conducted in Ward 29 of Shamva District in Zimbabwe. Epidemic
preparedness and response were assessed using the Zimbabwean epidemic
preparedness and response guidelines. RESULTS: The sociodemographic
characteristics of all participants were similar, except for gender. The risk
factors for contracting malaria were performing early morning chores (odds ratio
(OR) 2.75; 95% confidence interval (CI) 1.20 - 6.32), having a body of water near
the home (OR 3.41; 95% CI 1.62 - 7.20) and having long grass near the home (OR
2.61; 95% CI 1.10 - 6.37). Protective factors were staying indoors at night (OR
0.13; 95% CI 0.06 - 0.28) and staying in a sprayed home (OR 0.36; 95% CI 0.21 -
0.92). All cases were diagnosed with a malaria rapid diagnostic test. All
complicated cases were treated with quinine. Four out of 58 uncomplicated cases
were treated with quinine. The rest were treated with co-artemether. There was no
documentation of the outbreak response by the district health executive.
Respraying (indoor residual spraying) was carried out, with a coverage of 78% of
rooms sprayed. One nurse out of seven at Wadzanayi Clinic was trained in
integrated disease surveillance and response, and malaria case management.
District malaria thresholds were outdated. Malaria commodities such as drugs and
sprays did not have reorder limits. CONCLUSION: This study re-emphasises the
importance of environmental- and personal-level factors as determinants of
malaria. Poor out-break preparedness and response may have propagated the malaria
outbreak in this setting. Health education and the use of mosquito repellants
should be emphasised. Larvicide may reduce the malaria burden. Epidemic
preparedness and response need to be strengthened. Outbreak investigation remains
important. This study emphasises the need for malaria interventions to be
tailored to locally prevailing determinants to avert outbreaks.
PMID- 28492124
TI - Predicting postoperative haemoglobin changes after burn surgery.
AB - BACKGROUND: Burn surgery is associated with significant blood loss and fluid
shifts that cause rapid haemoglobin (Hb) changes during and after surgery.
Understanding the relationship between intraoperative and postoperative (day 1)
Hb changes may assist in avoiding postoperative anaemia and unnecessary peri
operative blood transfusion. OBJECTIVE: To describe the Hb changes into the first
day after burn surgery and to identify factors predictive of Hb changes that
would guide blood transfusion decisions. METHODS: This was a single-institution,
retrospective cohort study that included 158 patients who had undergone burn
surgery. Hb was measured at the start and end of surgery, and on the first day
(16 - 32 hours) after surgery, and the results were analysed. Peri-operative
factors (Hb at the end of surgery, total body surface area operated on (TBSA-op),
fluid administration and intraoperative blood administration) were evaluated to
determine their association with Hb changes on the first day after surgery.
RESULTS: The mean (standard deviation) preoperative Hb was 10.6 (2.29) g/dL, the
mean postoperative Hb was 9.4 (2.01) g/dL, and the mean Hb on the first day after
surgery was 9.2 (2.19) g/dL. Median total burn surface area was 7% (interquartile
range 9%, min. 1%, max. 45%), with a mean body surface area operated on
(debridement area plus donor area) of 9.7%. Of the 158 patients, 26 (16%) had an
Hb <7 g/dL (transfusion trigger) on the first day after surgery. For patients
with a high (>=9 g/dL), intermediate (>=7 - <9 g/dL), or low (<7 g/dL) Hb
measurement at the end of burn surgery, those with an Hb below the transfusion
trigger on the first day after burn surgery were 0%, 27%, and 75%, respectively.
End-of-surgery Hb and TBSA-op strongly predicted the first day Hb level. In the
intermediate group, 55% of patients with a TBSA-op >=11% had an Hb below the
transfusion trigger on the first day after surgery. CONCLUSION: Hb at the end of
burn surgery was the best predictor of Hb on the first day after surgery.
Patients with an Hb <7 g/dL remained as such on the first postoperative day. Half
of the patients with an end-of-surgery Hb >=7 - <9 g/dL and who had >=11% TBSA-op
had an Hb <7 g/dL on the first postoperative day.
PMID- 28492125
TI - Influence of HIV and other risk factors on tuberculosis.
AB - BACKGROUND: Tuberculosis (TB) notification in South Africa has increased six-fold
over the past two decades, mainly because of the HIV epidemic. OBJECTIVES: To
describe the sociodemographic and outcome characteristics of TB patients, and to
identify risk factors associated with TB treatment outcomes stratified by HIV
status. METHODS: A cross-sectional study was used to analyse data from the Cape
Town Metro East geographical service area (GSA) electronic TB register (ETR.Net),
including adult patients aged >=15 years who initiated TB treatment between 1
July 2011 and 30 June 2012. RESULTS: TB case notification in the GSA was 922 per
100 000 population. Of the 12 672 TB patients registered, 50.5% were co-infected
with HIV. The death rate in co-infected patients was 5.4% v. 2.8% in HIV-negative
patients, the rate of treatment success 66.6% v. 73.5%, and the rate of
unfavourable treatment outcome 28.1% v. 23.7%. The Khayelitsha subdistrict had
the highest proportion of TB burden (37.0%) and co-infection (47.6%). Fourteen
percent of patients had extrapulmonary TB, 65.9% of whom were co-infected with
HIV. In the multivariate analysis, HIV infection (relative risk (RR) 1.2),
retreatment (RR 1.4) and sputum smear microscopy not done (RR 1.4) were
significantly associated with unfavourable treatment outcome. The Eastern (RR
0.9) and Northern (RR 0.7) subdistricts were less likely to have unfavourable
outcomes compared with Khayelitsha. In the stratified analysis, retreatment and
smear not done were significant risk factors for an unfavourable treatment
outcome in both co-infected and HIV-negative patients. CONCLUSIONS: The burdens
of both TB and co-infection were high in this community, although HIV prevalence
varied. Mortality was higher and treatment completion lower in co-infected
patients than in those who were HIV-negative. Co-infection, previous TB treatment
and smear not done were significant risk factors for an unfavourable outcome in
all patients.
PMID- 28492126
TI - Bacteria isolated from the airways of paediatric patients with bronchiectasis
according to HIV status.
AB - BACKGROUND: Knowledge of which bacteria are found in the airways of paediatric
patients with bronchiectasis unrelated to cystic fibrosis (CF) is important in
defining empirical antibiotic guidelines for the treatment of acute infective
exacerbations. OBJECTIVE: To describe the bacteria isolated from the airways of
children with non-CF bronchiectasis according to their HIV status. METHODS:
Records of children with non-CF bronchiectasis who attended the paediatric
pulmonology clinic at Chris Hani Baragwanath Academic Hospital, Johannesburg,
South Africa, from April 2011 to March 2013, or were admitted to the hospital
during that period, were reviewed. Data collected included patient demographics,
HIV status, and characteristics of the airway samples and types of bacteria
isolated. RESULTS: There were 66 patients with non-CF bronchiectasis over the 2
year study period. The median age was 9.1 years (interquartile range 7.2 - 12.1).
The majority of patients (78.8%) were HIV-infected. A total of 134 samples was
collected (median 1.5 per patient, range 1 - 7), of which 81.3% were expectorated
or induced sputum samples. Most bacteria were Gram negatives (72.1%). Haemophilus
influenzae was the most common bacterium identified (36.0%), followed by
Streptococcus pneumoniae (12.6%), Moraxella catarrhalis (11.1%) and
Staphylococcus aureus (10.6%). There were no differences between HIV-infected and
uninfected patients in prevalence or type of pathogens isolated. CONCLUSION:
Bacterial isolates from the airways of children with non-CF bronchiectasis were
similar to those in other paediatric populations and were not affected by HIV
status.
PMID- 28492128
TI - Validating the utilisation of venous bicarbonate as a predictor of acute kidney
injury in crush syndrome from sjambok injuries.
AB - BACKGROUND: Crush injury secondary to sjambok beatings is a well-described
phenomenon in southern Africa. Owing to a number of factors, it can result in
acute kidney injury (AKI). In 1992, Muckart et al. described a risk
stratification system using venous bicarbonate (VB) that can be used in the
management of these patients. OBJECTIVE: To validate this score in the modern era
of AKI risk stratification. METHODS: A retrospective study was performed on a
local trauma database from June 2010 to December 2012. All patients with crush
injury from sjambok/blunt instrument beatings were included in the analysis. VB
was compared with the Kidney Disease Improving Global Outcomes scoring system for
AKI. Serum base excess (BE) and creatine kinase were also examined as biomarkers.
The endpoints were the need for renal replacement therapy (RRT) and mortality.
RESULTS: Three hundred and ten patients were included. The overall mortality rate
was 1.9%, 14.8% of patients had AKI, and 3.9% required RRT. Both VB and BE
performed well in RRT prediction, with areas under the receiver operating
characteristic curve of 0.847 (95% confidence interval (CI) 0.756 - 0.938;
p<0.001) and 0.871 (95% CI 0.795 - 0.947; p<0.001), respectively. The sensitivity
and specificity of BE were 83.3% and 80.2% at an optimal cut-point of -7.25
mmol/L, while those of VB were 83.3% and 79.5% at an optimal cut-point of 18.85
mmol/L. VB was significantly different across the AKI risk groups (p<0.001), in
keeping with the original Muckart risk stratification system. CONCLUSION: The
risk stratification score using VB is valid and should continue to be used as a
tool in the management of patients with sjambok injuries. BE performs well in
predicting the need for RRT, with a value of <-7.25 mmol/L indicating severe
injury.
PMID- 28492127
TI - Obstructive pulmonary disease in patients with previous tuberculosis:
Pathophysiology of a community-based cohort.
AB - BACKGROUND: An association between chronic airflow limitation (CAL) and a history
of pulmonary tuberculosis (PTB) has been confirmed in epidemiological studies,
but the mechanisms responsible for this association are unclear. It is debated
whether CAL in this context should be viewed as chronic obstructive pulmonary
disease (COPD) or a separate phenotype. OBJECTIVE: To compare lung physiology and
high-resolution computed tomography (HRCT) findings in subjects with CAL and
evidence of previous (healed) PTB with those in subjects with smoking-related
COPD without evidence of previous PTB. METHODS: Subjects with CAL identified
during a Burden of Obstructive Lung Disease (BOLD) study performed in South
Africa were studied. Investigations included questionnaires, lung physiology
(spirometry, body plethysmography and diffusing capacity) and quantitative HRCT
scans to assess bronchial anatomy and the presence of emphysema (<-950 HU), gas
trapping (<-860 HU) and fibrosis (>-200 HU). Findings in subjects with a past
history and/or HRCT evidence of PTB were compared with those in subjects without
these features. RESULTS: One hundred and seven of 196 eligible subjects (54.6%)
were enrolled, 104 performed physiology tests and 94 had an HRCT scan. Based on
history and HRCT findings, subjects were categorised as no previous PTB (NPTB,
n=31), probable previous PTB (n=33) or definite previous PTB (DPTB, n=39).
Subjects with DPTB had a lower diffusing capacity (Delta=-17.7%; p=0.001) and
inspiratory capacity (Delta=-21.5%; p=0.001) than NPTB subjects, and higher gas
trapping and fibrosis but not emphysema scores (Delta=+6.2% (p=0.021), +0.36%
(p=0.017) and +3.5% (p=0.098), respectively). CONCLUSIONS: The mechanisms of CAL
associated with previous PTB appear to differ from those in the more common
smoking-related COPD and warrant further study.
PMID- 28492129
TI - Codeine misuse and dependence in South Africa: Perspectives of addiction
treatment providers.
AB - BACKGROUND: General practitioners are referring patients with codeine-related
problems to specialist treatment facilities, but little is known about the
addiction treatment providers, the kinds of treatment they provide, and whether
training or other interventions are needed to strengthen this sector. OBJECTIVES:
To investigate the perspectives of addiction treatment providers regarding
treatment for codeine misuse or dependence. METHOD: Twenty addiction treatment
providers linked to the South African Community Epidemiology Network on Drug Use
and the South African Addiction Medicine Society were contacted telephonically
and asked 20 questions. RESULTS: While many participants had received training in
pharmacological management of individuals with opioid dependence, only two had
received specific training on codeine management. Between half and two-thirds of
the treatment settings they worked in provided detoxification, pharmacotherapy,
psychosocial treatment and aftercare. Very few treatment settings offered long
term treatment for codeine misuse and dependence. Participants indicated that
over half of their codeine patients entered treatment for intentional misuse for
intoxication, and dependence resulting from excessive or long-term use. The main
barriers to patients entering treatment were seen as denial of having a problem,
not being ready for change, mental health problems, stigma, and affordability of
treatment. Participants identified a need for further training in how to manage
withdrawal and detoxification, treatment modalities including motivational
interviewing, and relapse prevention. CONCLUSIONS: Gaps in training among
treatment providers need to centre on how to manage withdrawal from codeine use
and detoxification, motivational interviewing and relapse prevention.
Interventions are needed to address barriers to entering treatment, including
user denial.
PMID- 28492130
TI - Osteogenesis imperfecta type 3 in South Africa: Causative mutations in FKBP10.
AB - BACKGROUND: A relatively high frequency of autosomal recessively inherited
osteogenesis imperfecta (OI) type 3 (OI-3) is present in the indigenous black
southern African population. Affected persons may be severely handicapped as a
result of frequent fractures, progressive deformity of the tubular bones and
spinal malalignment. OBJECTIVE: To delineate the molecular basis for the
condition. METHODS: Molecular investigations were performed on 91 affected
persons from seven diverse ethnolinguistic groups in this population. RESULTS:
Following polymerase chain reaction amplification and direct cycle sequencing,
FKBP10 mutations were identified in 45.1% (41/91) OI-3-affected persons. The
homozygous FKBP10 c.831dupC frameshift mutation was confirmed in 35 affected
individuals in the study cohort. Haplotype analysis suggests that this mutation
is identical among these OI-3-affected persons by descent, thereby confirming
that they had a common ancestor. Compound heterozygosity of this founder mutation
was observed, in combination with three different deleterious FKBP10 mutations,
in six additional persons in the cohort. Four of these individuals had the
c.831delC mutation. CONCLUSION: The burden of the disorder, both in frequency and
severity, warrants the establishment of a dedicated service for molecular
diagnostic confirmation and genetic management of persons and families with OI in
southern Africa.
PMID- 28492132
TI - The Determination of Sugars in Dairy Products: Development of a New Standard
Method for the International Dairy Federation and the Internal Organization for
Standardization.
AB - A method using high-performance anion-exchange chromatography (HPAEC) with a
pulsed amperometric detector (PAD) for the determination of mono- and
disaccharides is described. The method was accepted by the International Dairy
Federation and the Internal Organization for Standardization as a new work item
for the determination of sugars in dairy matrixes, and the Milk and Milk Products
technical committee of ISO/TC 34/SC 5 accepted the topic "Milk and milk products
Determination of the sugar contents - High-performance anion-exchange
chromatographic method (HPAEC-PAD)" as a new work item. The proposed method
consists of an aqueous ethanol extraction of the sugars in the dairy sample,
followed by clarification with Carrez I and II reagents. The clarified filtrate
is diluted and then directly introduced in the HPAEC-PAD system for
quantification of the sugars. A single-laboratory validation of the proposed
method has been scheduled for spring 2017.
PMID- 28492133
TI - Current Assays to Determine Free 25-Hydroxyvitamin D in Serum.
AB - The 25-hydroxylated metabolite of vitamin D is the best clinical indicator of
vitamin D status. For many years, emphasis has been on measuring total levels of
25-hydroxyvitamin D [25(OH)D], but recently, interest in measuring free 25(OH)D
as a potentially better marker of vitamin D status has arisen. Since the 1980s
when the first measurements of free 25(OH)D were made, little progress has been
made in the development of rapid, reliable methods to determine the levels of
free 25(OH)D. For many years, assessment of free 25(OH)D relied on calculations
using levels of total 25(OH)D, albumin, and vitamin D binding protein (VDBP), for
which many assays exist. However, because of vagaries in the measurement of VDBP
in particular and the assumption of a constant affinity of VDBP for the vitamin D
metabolites (which has been shown to be problematic), calculated values have
proved suspect. This changed a few years ago when a new immunoassay was developed
to measure free 25(OH)D directly. This review examines methods for determining
free 25(OH)D, the different methods used in clinical studies, and the
relationships between free 25(OH)D and other vitamin D metabolites and the
physiologic functions affected by vitamin D metabolites, such as bone cell
activity and turnover. The review also comments on the value of assessing free
25(OH)D and the efforts to standardize the assays.
PMID- 28492134
TI - Simplified 25-Hydroxyvitamin D Standardization and Optimization in Dried Blood
Spots by LC-MS/MS.
AB - Previous studies have assessed vitamin D status based on the 25-hydroxyvitamin D
[25(OH)D] concentration measured in samples from dried blood spots (DBSs). In 40
individuals participating in a clinical study, we compared 25(OH)D levels
measured from DBSs and in serum using an LC-MS/MS reference procedure in
collaboration with the Vitamin D Standardization Program. The main objective was
to simplify and optimize current methods to produce an assay that can be used as
a screening tool for 25(OH)D concentration assessment without derivatization. The
DBS 25(OH)D levels, compared to serum concentrations, were found to have 101%
accuracy overall, and the correlation coefficient (r) was 0.83 (P < 0.0001), with
a significant linear relationship. Free 25(OH)D and vitamin D binding protein
(VDBP) were assessed in the serum samples for potential correlations to the DBS
calculations: the levels of free 25(OH)D had moderate to strong correlation to
DBS and serum concentrations, with r values of 0.67 (P < 0.0001) and 0.76 (P <
0.0001), respectively. VDBP and hematocrit had no significant correlation to
either DBS or serum sample types, with r values <0.1. In conclusion, the use of
two DBSs and an increase in DBS sample size improved overall sample
representation without the need for derivatization, and produced an accurate and
robust method that can be used to screen 25(OH)D levels.
PMID- 28492135
TI - Ions in Wine and Their Relation to Electrical Conductivity Under Ultrasound
Irradiation.
AB - Change in electrical conductivity is considered a potential indicator for the on
line monitoring of wine aging accelerated by ultrasound, as determined in our
previous study; however, the exact mechanism of change is currently unclear. In
this study, the ion content and the total ionic strength were analyzed by ion
exchange chromatography to investigate the change mechanism of the electrical
conductivity of wine under ultrasound irradiation. The results indicate that the
changes in wine electrical conductivity during ultrasound treatment correlate
with the changes in the cations (Na+, K+, Ca2+, Mg2+, and NH4+) and in the anions
from the organic acids (malic acid, citric acid, tartaric acid, oxalic acid, and
formic acid) and inorganic acids (Cl-, SO42-, and PO43-), especially for the
ionic strength of the wine. Overall, electrical conductivity may be used to
reflect the chemical reactions related to wine aging to a certain extent because
the reactions can be initiated by the conversion of cations and by the
degradation or auxiliary function of organic acids.
PMID- 28492136
TI - Inhibition of ERK1/2 Signaling Impairs the Promoting Effects of TGF-beta1 on
Hepatocellular Carcinoma Cell Invasion and Epithelial-Mesenchymal Transition.
AB - Transforming growth factor-beta (TGF-beta) and ERK signaling have been implicated
in various human cancers including hepatocellular carcinoma, but the underlying
mechanism remains largely unclear. In this study, we aimed to explore the role of
ERK1/2 in the regulation of TGF-beta's promoting and suppressive activities in
HCC cells. Our data showed that treatment with TGF-beta1 enhanced invasion and
epithelial-mesenchymal transition (EMT) in HCC HepG2 cells, accompanied with
increased MMP9 production and activation of Smad2/3 and ERK1/2, but inhibited
tumor cell proliferation. These effects were eliminated by treatment with
SB431542, a TGF-beta inhibitor. Afterward, treatment with the MEK1/2 inhibitor
U0126 reduced the TGF-beta1-induced invasion and vimentin and MMP9 secretion in
HepG2 cells, without affecting the inhibitory effects of TGF-beta1 on HepG2 cell
proliferation. Moreover, inhibition of Smad2/3 expression attenuated TGF-beta1
induced cell invasion, ERK1/2 phosphorylation, and MMP9 production in HepG2
cells. However, knockdown of Slug only reduced cell invasion but did not affect
ERK1/2 activation and MMP9 secretion in HepG2 cells. These data indicate that TGF
beta1 activates ERK1/2 in HepG2 cells through the Smad2/3 pathway but not the
Slug pathway. In summary, our study demonstrates that inhibition of ERK1/2
signaling attenuates the promoting effects of TGF-beta1 on the metastatic
phenotypes of HCC cells without affecting its suppressive effects on HCC cell
proliferation. Therefore, we suggest that ERK1/2 may be used as a molecular
target for the treatment of TGF-beta-responsive HCC.
PMID- 28492137
TI - The Importance of 25-Hydroxyvitamin D Assay Standardization and the Vitamin D
Standardization Program.
PMID- 28492139
TI - Histone Demethylase JARID1B Is Overexpressed in Osteosarcoma and Upregulates
Cyclin D1 Expression via Demethylation of H3K27me3.
AB - JARID1B has been proven to be upregulated in many human malignancies and is
correlated with tumor progression. However, its expression and clinical
significance in osteosarcoma are still unclear. Thus, the aim of this study was
to explore the effects of JARID1B in osteosarcoma tumorigenesis and development.
In this study, we found that the expression levels of JARID1B in osteosarcoma
tissues were significantly higher than those in corresponding noncancerous bone
tissues. In addition, JARID1B upregulation occurred more frequently in
osteosarcoma specimens from patients with a poor prognosis. After JARID1B
transfection in osteosarcoma cells, cell proliferation was significantly promoted
in vitro and in vivo. On the contrary, knockdown of JARID1B inhibited cell
proliferation in vitro and tumor growth in vivo. JARID1B can also decrease the
G0/G1 phase cell numbers and increase the S and G2/M phase cell numbers. We
further demonstrated that JARID1B regulates cyclin D1 expression through
H3K27me3. These findings indicate that JARID1B may act not only as a novel
diagnostic and prognostic marker but also as a potential target for molecular
therapy in osteosarcoma.
PMID- 28492138
TI - Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of
Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway.
AB - Prostate cancer has become the most commonly diagnosed and the second leading
cause of cancer-related deaths in males. The long noncoding RNA second chromosome
locus associated with prostate-1 (SChLAP1) has been found to be overexpressed in
a subset of prostate cancer. However, the significance and mechanism of SChLAP1
in prostate cancer are not well known. In this study, we explored the role of
SChLAP1 in prostate cancer tissues, cell lines, and mouse models. The effect of
SChLAP1 on miR-198 and MAPK1 was specifically examined. We found that SChLAP1
expression was significantly increased in prostate cancer cells and tissues.
Knockdown of SChLAP1 promoted apoptosis and inhibited cell proliferation and
invasion in vitro and in vivo. In addition, a potential bonding site between miR
198 and SChLAP1 was predicted, and a low expression of miR-198 was found in
prostate cancer tissues and cells. Knockdown of SChLAP1 significantly increased
the expression of miR-198, and SChLAP1 overexpression markedly decreased it,
indicating that SChLAP1 acted as a negative regulator in the expression of miR
198. Furthermore, our results showed that SChLAP1 interacted with miR-198 and
subsequently modulated the MAPK1 signaling pathway in prostate cancer. In
conclusion, our study has identified a novel pathway through which SChLAP1 exerts
its oncogenic role in prostate cancer at the level of miRNAs and provided a
molecular basis for potential applications of SChLAP1 in the prognosis and
treatment of prostate cancer.
PMID- 28492140
TI - High-Dose Intramuscular Vitamin D Provides Long-Lasting Moderate Increases in
Serum 25-Hydroxvitamin D Levels and Shorter-Term Changes in Plasma Calcium.
AB - The best management of vitamin D deficiency, defined as a 25-hydroxyvitamin D
[(25(OH)D] level <50 nM, is unclear. Intramuscular (IM) injection of a large
bolus of vitamin D (>=100 000 IU) is used, but its safety is uncertain. In 10
adults given an IM injection of 600 000IU vitamin D3, we measured at baseline and
at 1, 2, 3, and 4 weeks postinjection the serum levels of vitamin D3, 25(OH)D3,
25(OH)D2, total 25(OH)D, 3-epi-25(OH)D3, and 24,25-dihydroxyvitamin D3
[24,25(OH)2D3] using a standardized LC with tandem MS (MS/MS) assay; serum levels
of 25(OH)D using the Abbott ARCHITECT i2000 immunoassay; and markers of bone
metabolism. Bone markers and 25(OH)D (immunoassay) were remeasured at 24 weeks.
All participants had baseline total 25(OH)D levels >50 nM. Serum 25(OH)D levels
increased at 3, 4, and 24 weeks postinjection, peaking at 4 weeks [mean +/- SEM
of 126 +/- 7.9 nM (immunoassay) and 100 +/- 5.5 nM (LC-MS/MS)] but generally
remained <125 nM, the upper limit recommended by the U.S. Institute of Medicine.
Serum 24,25(OH)2D3 levels increased at 3 and 4 weeks postinjection. Serum ionized
calcium levels were higher than baseline at 1, 3, and 4 weeks postinjection but
remained within the clinically normal range. Other biochemical parameters,
including other vitamin D metabolites, plasma alkaline phosphatase, and
parathyroid hormone levels, were unchanged. IM injection of a large bolus of
vitamin D effectively increases serum 25(OH)D levels without evidence of
metabolic abnormality.
PMID- 28492141
TI - Procaine Inhibits the Proliferation and Migration of Colon Cancer Cells Through
Inactivation of the ERK/MAPK/FAK Pathways by Regulation of RhoA.
AB - Colon cancer is one of the most lethal varieties of cancer. Chemotherapy remains
as one of the principal treatment approaches for colon cancer. The anticancer
activity of procaine (PCA), which is a local anesthetic drug, has been explored
in different studies. In our study, we aimed to explore the anticancer effect of
PCA on colon cancer and its underlying mechanism. The results showed that PCA
significantly inhibited cell viability, increased the percentage of apoptotic
cells, and decreased the expression level of RhoA in HCT116 cells in a dose
dependent manner (p < 0.05 or p < 0.01). Moreover, PCA increased the proportion
of HCT116 cells in the G1 phase as well as downregulated cyclin D1 and cyclin E
expressions (p < 0.05). In addition, we found that PCA remarkably inhibited cell
migration in HCT116 cells (p < 0.01). However, all these effects of PCA on cell
proliferation, apoptosis, and migration were significantly reversed by PCA + pc
RhoA (p < 0.05 or p < 0.01). PCA also significantly decreased the levels of p
ERK, p-p38MAPK, and p-FAK, but PCA + pc-RhoA rescued these effects. Furthermore,
the ERK inhibitor (PD098059), p38MAPK inhibitor (SB203580), and FAK inhibitor
(Y15) reversed these results. These data indicate that PCA inhibited cell
proliferation and migration but promoted apoptosis as well as inactivated the
ERK/MAPK/FAK pathways by regulation of RhoA in HCT116 cells.
PMID- 28492142
TI - Technical Note: Determination of Cholecalciferol (Vitamin D3) in Standard
Reference Material 3532 Calcium-Containing Solid Oral Dosage Form.
AB - Vitamin D is an important nutrient for many areas of human health and well-being,
including improved bone strength, muscle movement, cognitive function, and immune
health. The National Institute of Standards and Technology, in collaboration with
the National Institutes of Health Office of Dietary Supplements, has developed
SRM 3532 Calcium-Containing Solid Oral Dosage Form to help address the analytical
challenges seen by the dietary supplement communities for the determination of
vitamin D3 (cholecalciferol) and elements. Described here is the process to
assess the homogeneity and stability of the material, as well as the value
assignment of the vitamin D3 levels.
PMID- 28492143
TI - A Direct Assay for Measuring Free 25-Hydroxyvitamin D.
AB - Recent studies suggest that the concentration and genotype of vitamin D binding
protein (VDBP) are important factors that determine the bioavailability of 25
hydroxyvitamin D [25(OH)D] in blood. Accumulating data indicate that, e.g., in
pregnant women, hemodialysis patients, chronic kidney disease, liver failure, and
bladder and pancreatic cancers, the measurement of free 25(OH)D in serum provides
more relevant diagnostic information than measurement of total 25(OH)D. The aim
of this study was to develop and validate an ELISA for direct measurement of free
25(OH)D in serum. A simple and direct ELISA was developed, based on a two-step
immunoassay procedure performed in a microtiter plate. The assay has been
characterized in terms of precision (4-10% CV, according to concentration),
sensitivity (limits of blank = 0.5-1.0 pg/mL and LODs = 1.3-1.8 pg/mL), accuracy
(correlation to dialysis, ELISA = 0.99xdialysis-0.5 pg/mL, r2 = 0.74), cross
reactivity of the antibody for the D2 form (77%), and addition of both VDBP and
albumin (35-38% recovery upon addition of VDBP, 53-58% upon addition of albumin).
The assay has already been used in multiple studies, including its comparison
with calculation methods and in studies of patients with liver failure, different
ethnic groups, supplemented mice, respiratory diseases, and obesity. The free
25(OH)D ELISA can be used in studies as a valuable tool to establish the clinical
relevance of free 25(OH)D.
PMID- 28492144
TI - Clinical, Research, and Public Health Implications of Poor Measurement of Vitamin
D Status.
AB - There is widespread concern about the high prevalence of vitamin D deficiency
amid evidence to support that such a state may increase the risk of a wide range
of adverse health outcomes. Estimating the prevalence of deficiency, as well as
establishing links to health outcomes, requires the accurate and precise
measurement of 25-hydroxyvitamin D [25(OH)D] in serum or plasma. Accurate
measurement of 25(OH)D underlies the definitions of vitamin D deficiency,
insufficiency, and sufficiency and, thus, prevalence estimates. Imprecise
measurement of 25(OH)D in epidemiological research can result in incorrect null
findings of associations with disease. When associations with disease are found,
the inaccuracy of measurement forestalls defining the absolute level of 25(OH)D
that is associated with increased risk. For the clinician, both inaccuracy and
imprecision are problematic, because clinical care is most often based on a
single measurement to define vitamin D status. New initiatives to develop a
standard reference method and the assignment of "true" values to samples provide
a solution to these problems. The use of standardized assays in large population
studies will allow comparisons to be made between populations and over time that
have not previously been possible and will improve our understanding of the role
of vitamin D in health and disease.
PMID- 28492145
TI - Nuclear Medicine Imaging in Emergency Room and Priority Clinical Decision Making.
PMID- 28492146
TI - Vitamin D Deficiency in Alopecia Areata.
AB - OBJECTIVE: To compare the mean Vitamin D level in patients with alopecia areata
(AA) with age and gender controlled matched healthy controls. STUDY DESIGN: Case
control study. PLACE AND DURATION OF STUDY: Dermatology OPD, JPMC, from October
2014 to March 2015. METHODOLOGY: All the patients diagnosed of alopecia areata by
a trained dermatologist were selected. Controls were age and gender matched
healthy volunteers. Venous blood was drawn and sent to hospital laboratory for 25
(OH) vitamin D by enzyme immunoassay method on chemical analyser. Data was
recorded on SPSS version 16. Mann-Whitney test was applied to compare vitamin D
levels of cases and controls. P-value <0.05 was taken as significant. RESULTS:
There are 30 cases of AA, and 30 age and gender matched controls. The mean age of
our study group was 23.77 +/-8.86 ng/dL in patients and 24.03 +/-8.62 ng/dL in
the control group. Fifteen (50%) patients presented between 3-12 months of onset
of AA. Median (IQR) vitamin D level of cases was 13.5 (18.6) ng/dL and healthy
controls was 22.5 (16.25) (p=0.001). CONCLUSION: Serum Vitamin D levels were
significantly lower in patients with alopecia areata compared to healthy
controls.
PMID- 28492147
TI - Female Sexual Dysfunction in the Late Postpartum Period Among Women with Previous
Gestational Diabetes Mellitus.
AB - OBJECTIVE: To compare the status of female sexual dysfunction (FSD) between women
with a history of previous gestational diabetes mellitus (GDM) and those with
follow-up of a healthy pregnancy, using the female sexual function index (FSFI)
questionnaire. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY:
Department of Obstetrics and Gynecology, Fatih Sultan Mehmet Training and
Research Hospital, Istanbul, Turkey, from September to December 2015.
METHODOLOGY: Healthy sexually active adult parous females were included.
Participants were asked to complete the validated Turkish versions of the FSFI
and Hospital Anxiety and Depression Scale (HADS) questionnaires. Student's t-test
was used for two-group comparisons of normally distributed variables and
quantitative data. Mann-Whitney U-test was used for two-group comparisons of non
normally distributed variables. Pearson's chi-squared test, the Fisher
FreemanHalton test, Fisher's exact test, and Yates' continuity correction test
were used for comparison of qualitative data. RESULTS: The mean FSFI scores of
the 179 participants was 23.50 +/-3.94. FSFI scores and scores of desire,
arousal, lubrication, orgasm, satisfaction, and pain were not statistically
significantly different (p>0.05), according to a history of GDM and types of FSD
(none, mild, severe). HADS scores and anxiety and depression types did not
statistically significantly differ according to the history of GDM (p>0.05).
CONCLUSION: An association could not be found in FSFI scores between participants
with both the history of previous GDM and with healthy pregnancy; subclinical
sexual dysfunction may be observed in the late postpartum period among women with
a history of previous GDM. This may adversely affect their sexual health.
PMID- 28492148
TI - Immunohistochemical Expression of Epidermal Growth Factor Receptor in Head and
Neck Squamous Cell Carcinoma.
AB - OBJECTIVE: To determine the frequency of expression of epidermal growth factor
receptor (EGFR) by immunohistochemistry in head and neck squamous cell carcinoma
(HNSCC). STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Armed
Forces Institute of Pathology (AFIP), Rawalpindi, from September 2015 to March
2016. METHODOLOGY: Fifty-two cases of head and neck squamous cell carcinoma
diagnosed on H&E stain were included in the study. Patients' gender and age were
noted. Immunohistochemistry for EGFR was applied and the results were recorded.
The data were analyzed by using computer software program SPSS version 19.
Descriptive statistics, frequencies and percentages were calculated. RESULTS: Out
of the 52 patients of HNSCC, 37 patients were males and 15 females. The age of
the patients was between 21 and 80 years with an average age of 58.58 +/-12.63.
Out of 52 cases, 45 cases (86.53%) were positive for EGFR while 7 cases (13.46%)
were negative for EGFR. Significant statistical association was not seen between
the tumour grade and EGFR expression (p=0.162). CONCLUSION: The high expression
of EGFR in head and neck cancers among Pakistani patients suggests its value as a
therapeutic target. EGFR inhibitors have become well-known part of HNSCC
treatment; therefore, patients with EGFR positive HNSCC can be benefitted from
the therapy.
PMID- 28492149
TI - The Histopathological Parameters Affecting Biochemical Recurrence in Radical
Prostatectomies.
AB - OBJECTIVE: To determine the relationship between biochemical recurrence and other
histopathological factors in prostate cancer. STUDY DESIGN: Analytical study.
PLACE AND DURATION OF STUDY: Pathology and Urology Departments, Izmir Ataturk
Training and Research Hospital, between 2001 - 2013. METHODOLOGY: 117 cases
diagnosed with prostatic adenocarcinoma and treated by radical prostatectomy were
reviewed retrospectively for histopathological features; whereas, other
prognostic findings were noted. PSA levels and many other histopathological
parameters were assessed in order to put forth their effect on biochemical
recurrence. RESULTS: PSA level (p<0.001), tumor volume (p<0.001), Gleason score
(p<0.001), extraprostatic extension (p<0.001), perineural invasion (p<0.001),
ganglion involvement (p=0.040), vascular invasion (p<0.001), positive surgical
margins (p<0.001), presence of tertiary pattern (p=0.004) and the involvement of
the seminal vesicles (p<0.001) were found to be statistically related to the
pathological stage. Age, perineural invasion, high grade tertiary pattern,
intraluminal mucin, collagenous micronodules and foamy cytoplasmic changes were
unrelated to recurrence. CONCLUSION: Histopathological features can be helpful in
predicting prognosis in prostatic adenocarcinomas. However some of the
histopathological factors such as intraluminal mucin and foamy cytoplasmic
changes may not reflect high recurrence.
PMID- 28492150
TI - Selective Screening for Organic Acidurias and Amino Acidopathies in Pakistani
Children.
AB - OBJECTIVE: To determine the frequency of organic acidurais (OA) and amino
acidopathies (AA) in selected high-risk patients screened in two years. STUDY
DESIGN: Retrospective Observational study. PLACE AND DURATION OF STUDY: The Aga
Khan University Hospital (AKUH), Karachi, from January 2013 to December 2014.
METHODOLOGY: Patients with OA and AA were included in the study and patients with
IMDs other than OA and AA were excluded. Amino acids and organic acids were
analyzed on high performance liquid chromatography and gas chromatography-mass
spectrometry respectively. Clinical data and chromatograms of patients screened
for IMDs were reviewed by chemical pathologist and metabolic physician. RESULTS:
Eighty-eight cases (4.7%) were diagnosed including 41 OA (46.5%), 28 AA (31.8%)
and 19 others (21.5%) from 1,866 specimens analyzed. Median age of the patients
was 1.1 years, with high consanguinity rate (64.8%). Among OA, methyl CoA mutase
deficiency was diagnosed in 9 (10.2%) and was suspected in 2 (2.3%) cases. Five
(5.7%) cases of MHBD (2-methyl-3-hydroxybutyryl-CoA), 4 (4.5%) each of PPA
(propionic aciduria) and HMG-CoA lyase deficiency, 3 (3.4%) cases each of IVA
(isovaleric aciduria), multiple carboxylase deficiency, fructose-1, 6
biphosphatase deficiency, fumarase deficiency, GA-1 (glutaric aciduria type 1)
and 2 (2.3%) cases of EMA (ethyl-malonic aciduria). AA included 8 (9.1%) cases of
MSUD (maple syrup urine disease), 6 (6.8%) cases of CBS (cystathionine beta
synthetase) and UCDs (urea cycle disorders) each, 5 (5.7%) cases of
hyperphenylalaninemia and 3 (3.4%) cases of hyperprolinemia were reported. Other
inherited metabolic disorders included: 9 (10.2%) cases of intracellular
cobalamin defects, 2 (2.3%) cases each of alkaptonuria, Canavan's disease, SUCL
(succinate CoA ligase) deficiency, and 1 (1.1%) case each of DPD
(dihydropyrimidine) deficiency, GA-2, NKH (non-ketotic hyperglycinemia), AADC
(aromatic amino acid decarboxylase) deficiency. CONCLUSION: This study presents
frequency of OA and AA in the high-risk Pakistani pediatric population analyzed
locally.
PMID- 28492151
TI - Secretagogin (SCGN) Plasma Levels and their Association with Cognitive and Social
Behavior in Children with Autism Spectrum Disorder ASD).
AB - OBJECTIVE: To investigate the secretagogin (SCGN) plasma levels in children with
autism spectrum disorder (ASD) compared to age and gender-matched healthy
control, and its association with cognitive and social behaviors by using
childhood autism rating scale (CARS) and social responsiveness scale (SRS). STUDY
DESIGN: Case-control study. PLACE AND DURATION OF STUDY: Autism Research and
Treatment Center, Al-Amodi Autism Research Chair, Department of Physiology,
Faculty of Medicine, King Khalid University Hospital, King Saud University,
Riyadh, Saudi Arabia, from October 2015 to May 2016. METHODOLOGY: SCGN levels
were determined in the plasma of thirty-seven (37) autistic children using enzyme
linked immunosorbent assay (ELISA), categorized as mild-moderate and severe as
indicated by their CARS scores and compared with thirty (30) age and gender
matched control samples. Correlation between SCGN levels and different cognitive
and social behavior scales (CARS and SRS) was determined by Spearman's
correlation coefficient (r). RESULTS: The results indicated that autistic
children (n=37) had significantly (p= 0.005) lower plasma level of SCGN {45.7
(26.2) ng/ml [median (IQR)]} than those of healthy controls {n=30, 70.8 (48.6)
ng/ml [median (IQR)]}. Children with severe (n=28, 76%) as well as mild to
moderate autism (n=09, 24%) also exhibited significantly lower SCGN levels {47.5
(27) ng/ml [median (IQR)], p =0.014} and {45.7 (16.6) ng/ml [median (IQR)], p =
0.02)}, respectively than healthy controls {n=30, 70.8 (48.6) ng/ml [median
(IQR)]}. However, there was no significant difference between the SCGN levels of
children with mild to moderate and severe autism (p = 0.66). Spearman's
correlation coefficient (r) was used to determine the relationships between SCGN
levels and different variables (CARS, SRS). However, the results showed no
significant correlation between SCGN and these scales. (CARS, r=-0.03, p=0.86;
SRS, r=0.21, p=0.20). CONCLUSION: The low SCGN plasma levels in children with ASD
probably indicate that SCGN might be implicated in the pathogenesis of autism.
However, these data should be treated with caution until further investigations
are performed using larger sample sizes to determine whether the decrease in
plasma SCGN levels is a mere consequence of autism or it plays a pathogenic role
in the disease.
PMID- 28492152
TI - Effect of Stone Composition on the Outcomes of Semi-Rigid Ureteroscopy Using
Holmium: Yttrium-Aluminum-Garnet Laser or Pneumatic Lithotripsy.
AB - OBJECTIVE: To compare the effectiveness of laser lithotripsy (LL) and pneumatic
lithotripters (PL) in calcium oxalate (CaOx) and calcium phosphate (CaP) stones
and assess whether these stone compositions affect the outcomes of LL and PL.
STUDY DESIGN: Comparative, descriptive study. PLACE AND DURATION OF STUDY:
Istanbul Training and Research Hospital, Turkey, from August 2010 to August 2015.
METHODOLOGY: A total of 114 patients underwent ureteroscopy using LL and PL.
Fifty-eight (50.9%) had CaOx stones and 56 (49.1%) had CaP stones. The
lithotripters were compared in stone composition groups, and stone compositions
were compared in lithotripter groups. Patient characteristics, perioperative
parameters, and postoperative complications were compared. RESULTS: The baseline
patient and stone characteristics were similar in all groups. The operation time
of the PL and LL for the patients with CaP stones (68.75 +/-32.88 and 44.48 +/
34.37 minutes, respectively) was significantly shorter than the operation time of
the PL and LL for the patients with CaOx stones (91.56 +/-30.54 and 65.75 +/
37.74 minutes, (p=0.012 and p=0.009, respectively). Moreover, the patients with
CaOx or CaP treated with LL 65.75+/-37.74 and 44.48 +/-34.37 minutes,
respectively) had significant shorter operation time than the PL (91.56 +/-30.54
and 68.75 +/-32.88 minutes, (p=0.046 and p=0.01, respectively). Stone-free rates
were similar in all groups. The PL for the patients with CaP stones caused more
postoperative fever and infection than the other groups (p=0.050). CONCLUSION:
Though both PL and LL are effective in the treatment of CaOx and CaP stones, LL
had a significantly shorter operation and hospitalization time and complication
rates in patients with CaOx and CaP stones. So LL is a more feasible and safer
modality in the treatment of recurrent CaP stones.
PMID- 28492153
TI - Prognostic Value of p53 Expression Intensity in Urothelial Cancers.
AB - OBJECTIVE: To determine association of immunohistochemical expression intensity
of p53 with grade and stage of urothelial cancers. STUDY DESIGN: Descriptive
cross-sectional analytical study. PLACE AND DURATION OF STUDY: Pathology
Department, King Edward Medical University, Lahore, from January to December
2016. METHODOLOGY: Data of transurethral resection/radical cystesctomy urinary
bladder biopsies was collected. Clinical, radiological and cystoscopic findings
of patients were noted from patients' charts in the Urology Ward. Biopsies were
graded histologically according to WHO 2004 grading system. TNM system was used
for pathological staging. On selected slides, immunoshistochemistry for p53 was
applied. Nuclear immunoreactivity was considered positive if present in >10% of
tumor cells and negative if <10% of tumor cells. Intensity was considered weak
(less than 15% cells) and strong (more than 15% cells). Data was analyzed by SPSS
version 21. Linear-by-linear association was calculated between p53 expression
and stage of urothelial tumors, Chi-Square test was used to see association
between grade and intensity of p53. Qualitative variables, like grade and stage
of carcinoma along with p53 expression, were calculated in terms of frequencies
and percentages. P <= 0.05 was taken as significant. RESULTS: Out of the 70
patients, 61 (87%) were males and 9 (13%) females. Out of 25 low grade lesions, 4
(16%) cases were p53 positive; and out of 45 high grade lesions, 41 (91%) cases
were p53 positive. There was 33% (2/6 cases) positivity in Tis, 55% (16/29 cases)
in T1, 72% in T2 (21/29), and 100% in T3a (5/5 cases) and T3b (1/1 case). Strong
intensity of p53 staining was noted to be 5.4% (n=25) of low grade and 94.6%
(n=45) of high grade tumors. CONCLUSION: p53 expression was greater and more
frequently strong in higher grade and stage of urothelial carcinoma. It can be
used as a prognostic marker in predicting higher grade and stage of bladder
cancer.
PMID- 28492154
TI - The Efficacy and Safety of Iodine-125 Brachytherapy Combined with Chemotherapy in
Treatment of Advanced Lung Cancer: A Meta-Analysis.
AB - The aim of this study was to systematically review the efficacy and safety of
iodine-125 brachytherapy combined with chemotherapy in patients with advanced
lung cancer. PubMed, MEDLINE, EBSCO, FMJS and Web of Science were searched to
obtain randomized controlled trials (RCTs), published in English and Chinese,
until February 2016. The evaluating indicators were complete response (CR),
partial response (PR), stable disease (SD), progressive disease (PD), overall
response rate (ORR), disease control rate (DCR), one-year overall survival, two
year overall survival and adverse events. Revman 5.2 software was used for data
syntheses and analyses. A total of 296 patients enrolled in 5 RCTs were
ultimately included in this study based on our selection criteria, and 150
patients received chemotherapy alone, while another 146 patients received the
combination therapy of iodine-125 brachytherapy and chemotherapy. The results
showed that iodine-125 brachytherapy combined with chemotherapy was superior to
chemotherapy alone in CR (risk ratio [RR] = 3.66, 95% confidence interval [CI]:
2.08 to 6.44, p<0.001), PR (RR = 1.47, 95% CI: 1.16 to 1.86, p=0.001), ORR (RR =
1.85, 95% CI: 1.54 to 2.22, p<0.001), DCR (RR = 1.19, 95% CI: 1.10 to 1.29,
p<0.001), one-year overall survival (RR = 1.46, 95% CI: 1.12 to 1.92, p=0.006)
and PD (RR = 0.20, 95% CI: 0.09 to 0.43, p<0.001); meanwhile, there was no
significant difference in two-year overall survival (RR = 1.30, 95% CI: 0.72 to
2.37, p=0.39). In terms of adverse events, the combination therapy significantly
increased the incidence of neumothorax (RR = 4.93, 95% CI: 1.94 to 12.55,
p=<0.001); however, no significant differences were found in the incidence of
other adverse events. This study indicated that the combination therapy of iodine
125 brachytherapy and chemotherapy could improve the therapeutic efficacy of
advanced lung cancer without increasing the incidence of adverse events, except
pneumothorax.
PMID- 28492155
TI - An Audit to Evaluate the Image Quality of Magnetic Resonance of Knee at Radiology
Department of a Tertiary Care Hospital.
AB - : light of recommendations of ACR. STUDY DESIGN: Aclinical audit. PLACE AND
DURATION OF STUDY: Department of Radiology, Jinnah Hospital, Lahore, from August
2015 to February 2016. METHODOLOGY: Scans of 20 patients who underwent MRI of
knee in August 2015 were studied retrospectively to assess the quality of images
obtained in the first audit. Based on the findings of this audit, recommendations
were made and re audit was done 6 months later in February 2016 to look for
improvement in local practice. RESULTS: In the first audit, images were acquired
in all the three necessary planes and the sagittal and coronal images had
appropriate slice thickness, interslice gap as well as adequate anatomical
coverage in all the patients. However, FOV (field of view) was appropriately set
in 66% of cases in axial plane, 5% in sagittal plane, and 0% in coronal plane.
Also, the anatomical coverage was not upto the mark in axial plane with 13
studies (66%) having adequate superior coverage, and 16 cases (80%) having
recommended inferior anatomical coverage. The re audit performed 6 months later
showed improvement with 100% compliance to standards. CONCLUSION: The first audit
showed many shortcomings in acquiring of MRI data in patients undergoing knee MRI
with FOV requiring a decrease in all planes and anatomical coverage increase in
axial plane. These recommendations were made in departmental meetings and re
audit was done after 6 months. This second audit showed 100 % compliance.
PMID- 28492156
TI - Electrical Storm or Naxos Syndrome in an Adult Causing Recurrent Syncope.
AB - Among the rare and well-known causes of sudden cardiac death by malignant
arrthymias is a condition called arrhythmogenic right ventricular cardiomyopathy.
It commonly presents with right ventricular dilatation, dysfunction and
ventricular tachycardia of left bundle branch morphology due to fibro-fatty
infiltration of right ventricle in second to fifth decade of life, making it an
unrecognized and important cause of sudden cardiac death. Two rare variants of
arrhythmogenic right ventricular cardiomyopathy are Carvajal syndrome and Naxos
syndrome. Both variants have systemic manifestations. Being a rare variant of
arrhythmogenic right ventricular dysplasia, Naxos syndrome was initially
described in the families of the Greek island of Naxos. It is a recessive
disorder with cardio-cutaneous manifestations characterized by arrhythmogenic
right ventricular cardiomyopathy, palmoplantar keratoderma and wooly hair. We
report a rare case of Naxos syndrome in an adult patient presented with recurrent
episodes of palpitation and syncope.
PMID- 28492157
TI - Angiomyxolipoma of Tongue.
AB - Angiomyxolipoma is a rare histological variant of lipoma, characterized by
proliferation of adipose tissue associated with a variable amount of myxoid
stroma with numerous thick- and thin-walled blood vessels. An exhaustive
literature review could reveal only 12 cases of angiomyxolipoma affecting
subcutaneous tissue, subungual area and spermatic cord. In oral cavity, only 2
cases of angiomyxolipoma have been reported to date, one case in the buccal
mucosa and one case in the floor of the mouth. Hence, this is only the third case
of angiomyxolipoma affecting oral cavity and the first case of angiomyxolipoma of
the tongue. We report a case of a 51-year male presenting with a swelling on the
right lateral border of the tongue. The lesion was excised and microscopical
examination confirmed the diagnosis of angiomyxolipoma.
PMID- 28492158
TI - Metachronous Metastatic Renal Cell Carcinoma to the Jejunum Presenting with
Massive Lower Gastrointestinal Bleeding.
AB - Metastatic renal cell carcinoma (MRCC) is a rare cause of massive lower
gastrointestinal bleeding (LGIB). We report a 51-year man who underwent left
nephrectomy for renal cell carcinoma (RCC) 6 years ago. presenting with massive
LGIB. Preoperative abdominal computed tomography (CT) revealed small bowel mass.
Exploration of the abdomen revealed jejunal mass. Resection of the mass along
with the jejunal segment with end-to-end anastomosis was performed.
Histopathology of the jejunal mass confirmed MRCC. MRCC should be expected as a
source of massive LGIB in a patient with history of RCC. Surgical intervention
should not be delayed in a hemodynamically unstable patient and persistent
bleeding.
PMID- 28492159
TI - Iloprost Instillation in Two Neonates with Pulmonary Hypertension.
AB - Pulmonary hypertension may coexist with certain diseases in neonates. Iloprost
inhalation is one of the treatments which cause selective pulmonary
vasodilatation. Inhalation is not an easy way of drug administration in
mechanically ventilated infants; as some exhibit desaturations during inhalation.
Moreover, inhalation of drug requires cessation of mechanical ventilation, if
patient is on high frequency oscillatory ventilation. We presented two patients
with pulmonary hypertension; term baby with congenital diaphragmatic hernia and
preterm baby with respiratory distress syndrome; who had iloprost instillation
during mechanical ventilation treatment. Iloprost instillation was well tolerated
with no side effects in the term patient with diaphragmatic hernia; whereas
severe blood pressure fluctuations were observed in the preterm infant. This
report may courage administration of iloprost in term neonates with resistant
pulmonary hypertension.
PMID- 28492160
TI - Very Late Stent Thrombosis: Is There Any Limit, When to Stop Antiplatelet
Therapy?
PMID- 28492161
TI - Cardiologist-Dentist Interaction in the Dental Management of Immunocompromised
Cardiac Patient.
PMID- 28492162
TI - Spuriously Low HbA1C Levels in a Type II Diabetes Patient Taking Dapsone.
PMID- 28492163
TI - Antibiotic Resistance Pattern of Acinetobacter spp. Strains Isolated from Blood
Infections in Shahid Sadoughi Hospital, Yazd, Iran.
PMID- 28492164
TI - Ultrasound-Guided Vascular Access: An Evolving Standard of Care Clinical
Practice, which is Extremely Under-Utilized in Pakistan.
PMID- 28492165
TI - [The contribution of legal medicine in child protection: Presentation of a
multidisciplinary approach].
AB - INTRODUCTION: Maltreatment is a complex issue and therefore, requires a
multidisciplinary approach, which has been commonly used in North America since
the 1980s but remains unsystematic in France. Since 1999, the Centre d'Accueil en
Urgence des Victimes d'Agression (emergency unit for victims of assault) of the
Bordeaux University Hospital has brought together various medical, paramedical,
and social actors on this issue. A standardized psychosocial assessment procedure
has been introduced and is detailed in this paper, and was consistently conducted
in all cases of suspicion of abuse on a minor. METHOD: The authors studied 74
cases of minors having undergone a psychosocial assessment following suspicions
of maltreatment between 1 July 2014 and 30 June 2015 that were not referred to
the courts. RESULTS: Forty-five girls and 29 boys, mean age 7 years, claiming
mainly (75 %) to have been subjected to sexual violence, were addressed to us by
internal partners (n=15) and external partners (n=37) and 22 who came to our unit
by self-referral. Following our assessment, 35 returned to their home and 36 went
to court following a police complaint (n=17) and a report filed to the public
prosecutor of the Republic (n=19). Three of these cases were subjected to a
report on matters of concern sent to the departmental council. CONCLUSION: Given
the absence of a national consensus on the methodology used for assessing
suspicions of maltreatment on minors, our psychosocial assessment can facilitate
the task with its peer review as well as the detection and judicialization of the
maltreatment. The authors also highlight the recent modification of article 226
14 of the Penal Code, which aims at protecting professionals reporting matters to
legal authorities from any legal proceeding, except if it is established that the
individual did not act in good faith.
PMID- 28492166
TI - [Violence in schools: Prospective study conducted in an emergency reception
center for victims of aggression].
AB - INTRODUCTION: Although violence in schools is quite well conveyed in the media,
the French literature data remain patchy, and the figures available arise mainly
from surveys of victimization. This study had two main purposes: to add to the
national epidemiological data on this phenomenon and to emphasize the actions
that can be undertaken by the practitioner facing such events. MATERIAL AND
METHODS: This was a prospective descriptive study that was conducted from
September 1st, 2014, to June 30, 2015, in a single center, the CAUVA, an
emergency center within the Bordeaux University Hospital for victims of assault.
Included in the study was any person alleging acts of violence on the way to
school, in the neighborhood, or within the school itself, and who was examined at
the CAUVA following a judicial requisition. An anonymized questionnaire was
distributed during the consultation. RESULTS: We collected 41 questionnaires over
a 10-month period with 70.7% males (n=29) and 29.3% females (n=12), with a mean
age of 14 years and 5 months (range, 7-49 years). The subjects included two
teachers and 39 students. The time between the event and the forensic examination
at CAUVA was mostly less than or equal to 7 days (n=18), between 7 and 15 days
(n=14), 15 and 30 days (n=6), and more than 30 days (n=3). Twenty-six attacks
(63%) took place inside the school - 21 middle schools - eight near the school,
and seven between the student's home and the school. Inside the school, the
events took place during a break (n=15), in the classroom (n=9), and during
cultural outings (n=2). For one student out of two (n=25), the event reported was
the first with acts of physical (n=37), psychological (n=20), or sexual violence
(n=2). In 14.6% (n=6) of the cases, the assailant was a teacher and in almost 83%
(n=34) of the cases it was another student, either from the same class (n=19) or
another class (n=14), or a former student (n=1). CONCLUSION: This study brings
out trends that can assist the practitioner during consultations related to
violence. Screening, the description of the physical and psychological impact,
and dispatching to a medical-legal unit for complex situations or sexual assaults
contribute to making the general practitioner, the emergency physician, the
pediatrician, and the school doctor key players in the treatment and management
of violence.
PMID- 28492167
TI - Management of cholestatic pruritus in children with Alagille syndrome: Case
report and literature review.
AB - Alagille syndrome causes intractable pruritus and disfiguring xanthomas because
of retained bile acids and cholesterol. Drug therapy in addition to surgical
intervention may be effective in many patients in reducing serum bile acids,
cholesterol levels, pruritus, and skin xanthomas. In this report, we describe a
child with Alagille syndrome who presented with severe pruritus and xanthomas as
a consequence of severe hypercholesterolemia and discuss the treatment
modalities.
PMID- 28492168
TI - Accidental intravenous administration of paracetamol syrup in a child.
AB - OBJECTIVE AND IMPORTANCE: Medication administration errors occur frequently in
clinical practice. CLINICAL PRESENTATION: An 18-month-old child presented with
vomiting and diarrhea. Due to a rise in temperature, paracetamol syrup was
prescribed, but a nurse inadvertently administered the drug IV through the
peripheral venous access. INTERVENTION: The child was referred to the pediatric
intensive care unit where his clinical condition improved and the risk of
peripheral venous and pulmonary embolism was excluded. CONCLUSION: The use of
specific oral syringes should become a standard of practice in every healthcare
organization and more supervision of new nurse graduates is necessary. Also,
attention to the relationship with parents should be guaranteed because the
communication of medical errors is a highly challenging aspect of these errors.
PMID- 28492169
TI - [Learning disorders in ADHD: How are they related?]
AB - Learning difficulties in general and learning disabilities in particular are
almost constant in attention deficit disorder with or without hyperactivity
(ADHD). Despite a major research effort, the extent and diversity of these
comorbid events still raise many questions about the exact nature of their
pathogenetic condition (simple consequences of ADHD or specific related
disorders?) and consequently the best way to support them. This article aims to
present a brief review of the current data.
PMID- 28492170
TI - Reticulated acanthoma with sebaceous differentiation.
PMID- 28492171
TI - Eight cases of cutaneous leishmaniasis due to Leishmania infantum with protean
presentation.
PMID- 28492172
TI - Fingernail involvement in adult Langerhans cell histiocytosis.
PMID- 28492173
TI - Disease ecology of Hematodinium perezi in a high salinity estuary: investigating
seasonal trends in environmental detection.
AB - The blue crab Callinectes sapidus has seen a general decline in population
levels. One factor influencing mortality is infections by Hematodinium perezi, a
dinoflagellate parasite. A 2 yr study was conducted in 2014 and 2015 to monitor
H. perezi DNA within the Maryland (USA) coastal bays, comparing seasonal cycles
in the abundance of parasite DNA in environmental samples to parasite presence in
host blue crabs. A late summer to early fall peak in H. perezi infections in blue
crabs was observed, consistent with previous work. Infection intensities matched
this trend, showing a slow progression of low intensity infections early in the
year, with a peak in moderate and heavy infections occurring between July and
September, for both years. It was hypothesized that the peak in water column
occurrence would coincide with those months when infection intensities were
highest in blue crabs. As the peaks in water column occurrence were in July 2014
and August-September 2015, this is consistent with sporulation being the primary
contributor to environmental detection in summer months. An additional peak in
environmental detection occurred in both years during the early spring months,
the cause of which is currently unknown but may be related to infections in
overwintering crabs or alternate hosts. Several new crustacean hosts were
identified within this estuary, including grass shrimp Palaemonetes spp. and the
sand shrimp Crangon septemspinosa, as well as the mud crab Dyspanopeus sayi.
Improved knowledge of this disease system will allow for better management of
this important fishery.
PMID- 28492174
TI - Hematodinium spp. infections in wild and cultured populations of marine
crustaceans along the coast of China.
AB - The parasitic dinoflagellate Hematodinium spp. infects a broad range of marine
crustaceans. Its epidemics have impacted wild populations of various commercial
fishery species around the world and the sustainability of mariculture in China.
To study the epidemiology of Hematodinium spp. in marine crustaceans along the
coast of China, we conducted a broad survey of wild and cultured stocks of major
crustacean species in 2013 to 2015. Hematodinium sp. infections were identified
in wild stocks of Portunus trituberculatus from Huludao, Laizhou, Qingdao,
Yangtze River Estuary and Zhoushan, and Scylla paramamosain from Shantou; and
cultured stocks of Portunus trituberculatus and Penaeus monodon from a
polyculture pond in Qingdao. In the polyculture pond, Hematodinium sp. infections
were observed in Portunus trituberculatus from June until October, with peak
prevalence (up to 90%) observed in late July to early August. Furthermore,
Hematodinium sp. infection was identified for the first time in the giant tiger
prawn Penaeus monodon in the polyculture system during the disease outbreak.
Phylogenetic analysis indicated that the Hematodinium isolate infecting Penaeus
monodon was identical to the isolate infecting the co-cultured Portunus
trituberculatus, and it was grouped into H. perezi genotype II together with the
other isolates reported in China. The Hematodinium sp. isolated from Portunus
trituberculatus appeared to have similar life stages as the H. perezi genotype
III isolated from the American blue crab Callinectes sapidus. Our study indicates
that outbreaks of Hematodinium disease can be a significant threat to the widely
used polyculture system for decapods in China that may be particularly vulnerable
to such generalist pathogens.
PMID- 28492175
TI - Risk factors associated with white spot syndrome virus outbreaks in marine shrimp
farms in Rayong Province, Thailand.
AB - The purpose of this study was to determine risk factors for white spot disease
(WSD) in Rayong, Thailand. A study was conducted from October 2014 to March 2015
to identify potential farm-level risk factors using a validated questionnaire. We
completed 1 questionnaire for each farm; a total of 38 questionnaires from the
case farms and 127 questionnaires from the control farms were collected. The
results showed that the presence of WSD in previous crops and the use of seawater
were risk factors (p < 0.01), indicating that the environment plays an important
role in WSD outbreaks in Rayong. Good management practices for pond preparation
and other mitigation steps should be part of a control measure program for WSD in
this region.
PMID- 28492176
TI - Morphological re-description and phylogenetic relationship of five myxosporean
species of the family Myxobolidae infecting Nile tilapia.
AB - Freshwater fish have a major economic and nutritional importance worldwide.
Myxosporeans are highly dangerous parasites that infect different fish species,
causing severe damage to a large number of economically important species,
especially in aquaculture. We conducted a survey of myxosporean parasites
infecting Nile tilapia Oreochromis niloticus (Perciformes: Cichlidae) collected
from different localities along the River Nile passing through Giza province,
Egypt. Out of 100 fish specimens collected, 45 were found to be naturally
infected with these parasites in the region of the trunk kidney. Light
microscopic examination revealed the presence of 5 distinct myxosporean species
belonging to 2 different genera, viz. Myxobolus and Triangula, belonging to the
family Myxobolidae; all 5 species have been previously described. Morphological
characteristics, host specificity and geographical distribution, tissue tropism,
and molecular analysis of the partial sequence of small subunit ribosomal DNA
gene revealed that the recovered myxosporean species described herein were
genetically distinct from other myxozoan species but had 95% sequence similarity
to M. cerebralis. Also, phylogenetic analysis placed the present myxosporean
species in the freshwater Myxobolus clade, which is a sister group of freshwater
Myxobolus/Henneguya species.
PMID- 28492177
TI - Characterization of Aliivibrio fischeri strains associated with disease outbreak
in brill Scophthalmus rhombus.
AB - Three bacterial isolates were recovered from a disease outbreak with high
mortality affecting brill Scophthalmus rhombus (Linnaeus, 1758). Moribund fish
showed no external signs of disease, but plentiful haemorrhages were observed in
liver. On the basis of phenotypic and genotypic characterization, the isolates
were identified as Aliivibrio fischeri. The phenotypic profile of the isolates
was basically similar to that of the type strain of this species, although some
discrepancies were observed, mainly in the BIOLOG GN profile. The main cellular
fatty acids of strain a591 were also consistent with this species. The highest
16S rDNA sequence similarities were recorded with the type strain of A. fischeri
(99.07%); other Aliivibrio species showed similarity values below 96%. The
highest sequence similarities with gyrB, rpoD and recA genes were also recorded
with A. fischeri type strain (99.31, 98.99 and 95.29% similarity, respectively).
DNA-DNA hybridization assays confirmed that these isolates belong to A. fischeri;
levels of DNA relatedness were 73.5 to 86.2% with isolate a591 (reciprocal values
of 86.9 to 99.04%). Finally, a virulence evaluation of the isolates using
Senegalese sole fry was also performed; significant mortalities (100% mortality
within 5 d) were recorded by intraperitoneal injection, but only with high doses
of bacteria (2 * 106 cfu g-1 body weight).
PMID- 28492178
TI - Isolation of Bdellovibrio and like organisms and potential to reduce acute
hepatopancreatic necrosis disease caused by Vibrio parahaemolyticus.
AB - Acute hepatopancreatic necrosis disease, a severe disease of shrimp, is caused by
Vibrio parahaemolyticus (AHPND Vp), a halophilic bacterium harboring a plasmid
that contains toxin genes homologous to Photorhabdus insect-related toxins. We
obtained 9 isolates of Bdellovibrio and like organisms (BALOs) from water and
sediment samples in Thailand. Using 16S rRNA sequencing, all of the organisms
were identified as Bacteriovorax spp. and were able to attack all tested AHPND Vp
isolates. In addition, their various susceptible hosts, including Gram-positive
and Gram-negative bacteria, were observed. The optimal ratio for interaction
between the Bacteriovorax isolate BV-A and AHPND Vp was determined to be 1:10.
The suitable conditions applied for co-culture between BV-A and AHPND Vp were 30
degrees C, 2% NaCl, and pH 7.6. The capability of BV-A to reduce numbers of AHPND
Vp in vitro was observed in co-culture after incubation for 2 d and continued
until the end of the incubation period. In vivo, BV-A was able to reduce
mortality of shrimp post-larvae infected with AHPND Vp. In addition, BV-A
significantly decreased the formation of biofilm by AHPND Vp. These findings
provide evidence for using Bacteriovorax as a biocontrol of AHPND Vp in shrimp
aquaculture.
PMID- 28492179
TI - Virulence variation among strains of the emerging infectious fungus
Batrachochytrium dendrobatidis (Bd) in multiple amphibian host species.
AB - Emerging infectious diseases have been documented in numerous plant and animal
populations. The infectious disease amphibian chytridiomycosis, caused by the
fungus Batrachochytrium dendrobatidis (Bd), is associated with global amphibian
population declines. While much Bd-amphibian research has centered on response
variation in hosts, a paucity of information exists on how variation in the
pathogen, such as strain differences, affects infection dynamics. To examine how
different Bd strains may differentially impact multiple hosts, we conducted
laboratory experiments to measure 2 infection outcomes, viz. host survival and
pathogen load, in 3 amphibian host species (Pacific treefrog, western toad, and
Cascades frog) after exposure to 3 different Bd strains (an additional fourth Bd
strain was tested in toads only). Our results confirm that the infection response
differs among host species. Western toads experienced significant mortality, but
Pacific treefrogs and Cascades frogs did not. Interestingly, our experiment also
captured strain-dependent virulence variation but only in 1 host species, the
western toad. Increased mortality was observed in 2 of the 4 Bd strains tested in
this host species. Toads were also the only host species found to have variable
pathogen load dependent on strain type; individuals exposed to the Panama strain
harbored significantly higher loads compared to all other strains. These findings
underscore the dynamic nature of Bd infection, showing that virulence can vary
contingent on host and strain type. We highlight the importance of both host- and
pathogen-dependent factors in determining overall infection virulence and show
the need for in vivo testing to fully assess pathogenicity.
PMID- 28492180
TI - Batrachochytrium dendrobatidis is present in Poland and associated with reduced
fitness in wild populations of Pelophylax lessonae.
AB - The fungus Batrachochytrium dendrobatidis (Bd) is a pathogen associated with
global declines of amphibians. We used qPCR to detect Bd in 255 samples from 10
Polish populations of 8 species. We found Bd infection in 3 species (Bombina
variegata, Pelophylax lessonae, P. esculentus). The infection intensity in P.
lessonae reached a maximum of 58400 genomic equivalents of zoospores (GE), and
the 2 most heavily infected individuals died. Previous observations of the
populations that included infected individuals showed reduced body size, failure
to reproduce, and mortalities of adults. These data highlight the importance of
emerging diseases, and the need to recognize them as an important factor in
conservation of the genus Pelophylax in Poland and Central and Eastern Europe.
PMID- 28492181
TI - Coinfection by Streptococcus phocae and cetacean morbillivirus in a short-beaked
common dolphin Delphinus delphis.
AB - We describe gross, histopathological, and immunohistochemical features of
Streptococcus phocae and cetacean morbillivirus coinfection in a short-beaked
common dolphin Delphinus delphis. Major gross findings were cutaneous purulent
nodules in the tail fluke, vegetative mitral valve endocarditis, and presumed
postpartum pyometra. Histologic examination revealed bacterial septicemia
characterized by widespread intravascular coccoid bacterial emboli. These were
associated with fibrinonecrotizing to pyogranulomatous dermatitis and
panniculitis, embolic pneumonia, neutrophilic and lymphoplasmacytic
meningochoroiditis, random neutrophilic hepatitis, lymphoplasmacytic myocarditis
and epicarditis, necrotizing adrenalitis, suppurative endometritis, and
multicentric reactive lymphadenopathy. Bacteriology and molecular analysis with
sequencing of the 16S rRNA gene identified S. phocae from lung, brain, and
adrenal gland tissue. Immunohistochemical analysis for morbillivirus detection
revealed positive immunolabeling in the epithelium of the choroid plexus of the
fourth ventricle. Published reports on S. phocae infection in cetaceans are rare,
and pathological details are limited. The present case indicates that S. phocae
has potential pathogenic capacity in common dolphins. The pathogenesis is
proposed to have involved cutaneous penetration after a skin trauma, leading to
initial cutaneous disease and eventual systemic infection.
PMID- 28492182
TI - Hexagonal boron nitride: a promising substrate for graphene with high heat
dissipation.
AB - Supported graphene on a standard SiO2 substrate exhibits unsatisfactory heat
dissipation performance that is far inferior to the intrinsic ultrahigh thermal
conductivity of a suspended sample. A suitable substrate for enhancing thermal
transport in supported graphene is highly desirable for the development of
graphene devices for thermal management. By using molecular dynamics simulations,
here we demonstrate that bulk hexagonal boron nitride (h-BN) is a more appealing
substrate to achieve high performance heat dissipation in supported graphene.
Notable length dependence and high thermal conductivity are observed in h-BN
supported single-layer graphene (SLG), suggesting that the thermal transport
characteristics are close to that of suspended SLG. At room temperature, the
thermal conductivity of h-BN-supported SLG is as high as 1347.3 +/- 20.5 Wm-1 K
1, which is about 77% of that for the suspended case, and is more than twice that
of the SiO2-supported SLG. Furthermore, we find that the smooth and atomically
flat h-BN substrate gives rise to a regular and weak stress distribution in
graphene, resulting in a less affected phonon relaxation time and dominant phonon
mean free path. We also find that stacking and rotation significantly impacts the
thermal transport in h-BN-supported graphene. Our study provides valuable
insights towards the design of graphene devices on realistic substrate for high
performance heat dissipation applications.
PMID- 28492183
TI - Evaluation of [Formula: see text] enrichment values obtained with an oral breath
test under conditions of impaired gastric functioning.
AB - Gastric emptying can be assessed by an oral administration of a 13C labeled
substrate and its response in the expiratory release of the oxidation product
[Formula: see text]. Impaired gut function, reflected, for example, in an
intolerance against enteral nutrition may delay or discontinue gastric emptying,
potentially leading to multiple peaks in the time profile of expiration. The
resulting profile cannot be analyzed by the usual data evaluation that is based
on a 'beta exponential' (BEX) function. We developed a new approach that better
reflects the underlying physiology. It allows a flexible time profile of gastric
release and considers a transient [Formula: see text] retention in different
compartments as well as an incomplete recovery of [Formula: see text] in the
expiration. Parameters that describe the distribution/retention kinetics cannot
be determined based on the same breath data that were used to estimate emptying.
To enable the determination of the kinetic parameters, they were constrained to
match published data using a Bayesian statistical analysis. The applicability of
the new model was compared with BEX for healthy subjects. BEX fails to explain
the observed data and, compared to the new approach, overestimates the speed of
emptying. Predictive accuracy under impaired gastric motility was explored using
synthetic data. Only the new approach can reproduce a multiphase absorption
profile. When routine benchtop equipment was used for measurements, then the rate
limiting step for precision in the estimate of emptying is the quality in the a
priori estimate for kinetic parameters rather than precision in measurements.
Only about 80% of the absorbed [Formula: see text] has to be released by
expiration. With these features, the new approach promises to widen the
applicability of breath tests for gastric emptying.
PMID- 28492184
TI - Thermal stability and optical properties of Si-Ge nanoparticles.
AB - Silicon-germanium is an important alloy mainly used in thermoelectricity and
electronics. However, its thermal and optical properties still need further
investigation at the nanoscale. That is why in this study, the size and shape
effect on the silicon-germanium phase diagram is investigated through the nano
thermodynamics methodology. As expected, the phase diagram undergoes a shift down
in temperature when the size decreases. However, it is demonstrated and explained
why the size effect on the solidus-liquidus curves is much stronger than the one
on the miscibility gap. Moreover, the shape effect is investigated for various
faceted polyhedral nanoparticles as well as for the sphere. Phase maps are then
provided as a function of the number of facets, at 4 and 10 nm, in order to
determine the structure of the alloy. Furthermore, the size and shape effects on
the energy bandgap are also studied. The energy bandgap increases when the size
is reduced. The cube and tetrahedral shapes exhibit the largest size effect on
the thermal and optical properties of the silicon-germanium alloy. Finally, this
paper provides a useful roadmap for experimentalists willing to tune the
properties of this alloy.
PMID- 28492185
TI - Reconnoitring the peer review process....
PMID- 28492186
TI - Recent research trends in dentistry.
AB - Research being an investigative process is employed to increase or revise the
current knowledge. Scientific research involves the conduct of a methodical study
to prove a hypothesis or give an answer to a specific question with the main aim
of finding definitive answer. This paper aims to advance knowledge of research
and develop interest in the postgraduate students. It also throws light on the
existing and emerging research strengths within a "high-performance culture." The
trends in dental research worldwide are looked at, in particular, a comparison
between the publication status in two countries, namely India and Australia. The
current themes in dental research are also discussed to facilitate future
projects for the aspiring pediatric dentists. Stress is given to the importance
of evidence-based dentistry as the current times call for high-quality and
ethical papers which are devoid of plagiarism. The common reasons for failure of
a research are explored and the strengthening factors are highlighted. Proper
planning of a pertinent research project is beneficial to the researcher as well
as the dental community.
PMID- 28492187
TI - Evaluation and association of serum iron and ferritin levels in children with
dental caries.
AB - BACKGROUND: Iron deficiency anemia accounts for 90% of all types of anemia in the
world. Although the prevalence has declined in recent years, it remains an
important pediatric public health problem. Iron deficiency has also been
associated with dental caries. It impairs salivary gland function causing reduced
salivary secretion and buffering capacity leading to increased caries activity.
AIM: The aim of the study is to explore an association between dental caries and
serum levels of iron and ferritin in children aged 3-12 years. Subjectsand
Methods: The study group included 120 children, hospitalized for uncomplicated
medical problems. Blood reports were evaluated to determine serum iron and
ferritin levels. Dental caries experience was assessed using deft index.
STATISTICAL ANALYSIS USED: The collected data were tabulated and analyzed using
Student's t-test and Pearson's correlation coefficient. RESULTS: Out of 120
children, 38 children showed low serum iron levels of which 31 children had
dental caries and nine out of 15 children in the high serum iron level group
showed dental caries. High ferritin levels were seen in three children among
which two children were caries-free and only one child had a low ferritin level
who also had a positive deft score. CONCLUSION: Based on the results, it was
concluded that there is an inverse association between serum iron levels and
dental caries whereas there is no association between serum ferritin levels and
dental caries.
PMID- 28492188
TI - Assessment of maternal risk indicators for the development of caries in their
children: A comparative, cross-sectional study.
AB - INTRODUCTION: Certain factors in mothers could be risk indicators for certain
diseases in their children. Hence, this study was undertaken to assess maternal
risk indicators for the development of early childhood caries in their children.
METHODOLOGY: A comparative, cross-sectional study was designed among 180 mother
child pairs attending various Anganwadi centers. Demographic, dietary, oral
hygiene practices and other necessary information were collected from mothers
using a structured questionnaire. Caries status and amount of plaque were
recorded through clinical examination. Nonstimulated saliva from mothers was
cultured for mutans streptococci (MS). Data were analyzed using SPSS version 17.
Chi-square, Student's t-test, and logistic regression were used. A P <= 0.05 was
considered statistically significant. RESULTS: In the study group, 73.3% of
mothers had caries as compared to only 53.3% mothers in control group. While mean
DMFT and mean DMFS of mothers in the study group was 3.78 +/- 3.91 and 8.37 +/-
12.2, respectively, the same for the mothers in the control group was 2.66 +/-
3.01 and 5.8 +/- 5.3. Sixty (66.7%) out of ninety mothers in the study group had
a high MS count as compared to only 40 (44.4%) mothers in control group (P =
0.003). CONCLUSION: The present study showed that high salivary MS count and
decay in mothers could be important risk indicators for the development of caries
in their children.
PMID- 28492189
TI - Restoring the voids of voices by signs and gestures, in dentistry: A cross
sectional study.
AB - AIMS: To help dentists to communicate with the hearing impaired patients, reach
an accurate diagnosis and explain the treatment plan by learning some signs and
gestures used in the nonverbal communication (NVC) and by devising some new signs
and gestures related to dentistry which shall be easy to learn and understand
both by the hearing impaired patients and the dentists. SETTINGS AND DESIGN: The
study was carried out on 100 hearing impaired students in the age group of 10-14
years in two special schools for hearing impaired children located in two
different states of India, where different spoken languages and different sign
languages are used. One dentist (expert dentist) was trained in the NVC and the
other dentist (non expert dentist) had no knowledge of this type of
communication, communicated the same sets of statements related to dentistry, to
the hearing impaired children. One1 translator was assigned to judge their
interactions. Students were asked to tell the interpreter at the end of each
signed interaction what they understood from the statement conveyed to them by
both the dentists. STATISTICAL ANALYSIS USED: All data collected were subjected
to statistical analysis using Chi-square test and odds ratio test. RESULTS: In
the special school of 1st state, the nonexpert dentist conveyed only 36.3% of the
information correctly to the students, whereas the expert dentist conveyed 83% of
the information correctly. In the special school of 2nd state, the nonexpert
dentist conveyed only 37.5% of the information correctly to the students, whereas
the expert dentist conveyed 80.3% of the information correctly. CONCLUSIONS:
Dentists should be made aware of the NVC and signs and gestures related to
dentistry should be taught to the hearing impaired students as well as the dental
students.
PMID- 28492190
TI - Decreased sleep in children and their behavioral problems in dental operatory.
AB - PURPOSE: This study was conducted to examine the contribution of inadequate sleep
and its associated factors, on behavior and cooperation of children in the dental
operatory. MATERIALS AND METHODS: A cross-sectional study was conducted on 100
healthy children at the time of their initial visit to the dental hospital,
ranging from preschoolers to adolescents. Data acquisition was done by a
questionnaire. Interview with the accompanying person was done to ask about the
sleep duration, naps, and sleep habits of the child. Children's behavior during
their preliminary examination was studied and categorized according to Frankl's
behavior rating scale. Data were analyzed by linear regression analysis and
Spearman's correlation with the aid of SPSS 16.0 software. RESULTS: Total
duration of sleep accounted for a small but significant contribution in
behavioral problems of children. Significant correlation was found between
duration of sleep and cooperative behavior in dental operatory (R = 0.478).
However, the duration of sleep was negatively correlated to the number of
siblings and socioeconomic status of the family. CONCLUSION: Children who had
shorter total sleep duration had increased behavioral problems in dental
operatory.
PMID- 28492191
TI - Prevalence of dental fear and its causes using three measurement scales among
children in New Delhi.
AB - INTRODUCTION: There is a great need for identifying fearful children, who often
present problems in patient management, thus affecting the quality of dental care
rendered to them. This study is unique in the way that dental fear was assessed
through three fear scales as research has suggested the use of more than one
scale because each scale has its own restrictions and is open to criticism. AIM:
The aim of this study was to evaluate dental fear and anxiety (DFA) among
children aged 3-14 years using three fear measurement scales. METHODS: The study
was conducted on children (3-14 years) who visited the Department of Pedodontics
and Preventive Dentistry at Maulana Azad Institute of Dental Sciences, New Delhi.
The DFA levels were measured using three fear measurement scales, i.e., facial
image scale (FIS), dental fear scale (DFS), and children's fear survey schedule
dental subscale (CFSS-DS). The dental behavior was estimated using the Frankl's
behavior rating scale (FBRS). RESULTS: The prevalence of dental fear according to
FIS was 14.3%, according to DFS was 22.6%, and according to CFSS-DS was 7.4%. In
assessment of the behavior of children in the clinics through FBRS, it was
observed that he maximum number of respondents (69.8%) showed Frankl's Rating 3
i.e. positive. In the DFS and CFSS-DS, the factor which caused most fear was
"feeling the needle injected" and "injections," respectively. CONCLUSION:
Assessment of dental fear is an extremely useful tool for the dental
practitioner, who can use it to customize the behavioral treatment and management
for child patients.
PMID- 28492192
TI - Association between family structure and oral health of children with mixed
dentition in suburban Nigeria.
AB - CONTEXT: Family structures can affect the oral health of the child. However,
little is known about the impact of the family structure on oral health of
children in Africa. AIMS: To determine the association between family structure,
twice daily toothbrushing, use of fluoridated toothpaste, caries, and oral
hygiene status of 5-12-year-old children resident in semi-urban Nigeria. SETTINGS
AND DESIGN: Secondary analysis of the data of 601 children recruited through a
household survey conducted in Ile-Ife, Nigeria. SUBJECTS AND METHODS: The
association between dependent variables (presence of caries, good oral hygiene,
use of fluoridated toothpaste, and twice daily toothbrushing) and the family
structure (parental structure, number of siblings, and birth rank) was
determined. STATISTICAL ANALYSIS USED: Simple and multivariate regression
analysis was used to determine the association. The regression models were
adjusted for age and gender. RESULTS: Children who were not primogenitor had
significantly reduced odds of using fluoridated toothpaste (AOR: 0.91; 95%
confidence interval [CI]: 0.85-0.97; P = 0.01) when compared with children who
were primogenitors or only children. Furthermore, having 0-2 siblings
significantly reduced the odds of having caries (AOR: 0.46; CI: 0.28-0.78; P <
0.001) when compared with children who had three or more siblings. Children who
used fluoridated toothpaste had significantly increased odds of having good oral
hygiene (AOR: 1.64; 95% CI: 1.18-2.28; P < 0.001). CONCLUSIONS: For this study
population, the number of siblings and the birth rank increased the chances of
having caries and use of fluoridated toothpaste, respectively.
PMID- 28492193
TI - Effectiveness of two different behavioral modification techniques among 5-7-year
old children: A randomized controlled trial.
AB - BACKGROUND: Dental fear is a common, essential, and inevitable emotion that
appears as a response to the stressful situation, which raises children's anxiety
level, resulting in reduced demand for pediatric dental care. AIMS: (1) To
compare and evaluate the effectiveness of customized tell-play-do (TPD) technique
with live modeling for behavior management of children. (2) To compare the
behavioral modification techniques in managing the children during their dental
visits. MATERIALS AND METHODS: Ninety-eight children aged 5-7 years were enrolled
in the study and randomly allocated into two groups. Phase I: first visit. Group
I - children were conditioned to receive various dental procedures using live
modeling followed by oral prophylaxis. Group II - TPD technique was introduced
with customized playing dental objects followed by oral prophylaxis. Phase II:
second visit. After 7 days interval, all the study subjects were subjected to
rotary restorative treatment. EVALUATION: Heart rate, Facial Image Scale (FIS),
and Venham-6-point index were used before intervention, after intervention, and
during dental procedure to quantify the anxious behavior. RESULTS: All 98
children after intervention underwent oral prophylaxis on first visit and rotary
restorative treatment on second visit. The average pulse rate, FIS, and Venham
scale scores were significantly lower among children who received TPD
intervention when compared to those who received live modeling intervention.
Unpaired t-test at 5% level of significance was considered as statistical
significance. CONCLUSIONS: TPD is effective in reducing children's fear and
anxiety about dental treatment, children enjoy playing with customized dental
object. Thus, to promote adaptive behavior, TPD could be an alternate behavioral
modification technique during pediatric dentistry.
PMID- 28492194
TI - Comparison of the Streptococcus mutans and Lactobacillus colony count changes in
saliva following chlorhexidine (0.12%) mouth rinse, combination mouth rinse, and
green tea extract (0.5%) mouth rinse in children.
AB - BACKGROUND: Compounds present in green tea have been shown to inhibit the growth
and activity of bacteria associated with oral infections. The purpose of this
study was to compare the efficacy of chlorhexidine (0.12%) mouth rinse and
combination (chlorhexidine and sodium fluoride) mouth rinse to that of green tea
extract (0.5%) mouth rinse in reducing the salivary count of Streptococcus mutans
and Lactobacillus in children. MATERIALS AND METHODS: The sample for the study
consisted of 75 school children aged 8-12 years with four or more (decay
component) of decayed, missing, and filled teeth index. Children were divided
randomly into three equal groups and were asked to rinse with the prescribed
mouth rinse once daily for 2 weeks after breakfast under supervision.
Nonstimulated whole salivary sample (2 ml) was collected at baseline and
postrinsing and tested for the colony forming units of S. mutans and
Lactobacillus. RESULTS: The results of the study indicate that there was a
statistically significant reduction in S. mutans and lactobacilli count in all
the three study groups. The statistically significant reduction in the mean S.
mutans and lactobacilli counts were more in 0.12% chlorhexidine group than in the
combination mouth rinse and 0.5% green tea mouth rinse group. There was no
statistically significant difference in the reduction of S. mutans and
lactobacilli count between combination mouth rinse group and 0.5% green tea mouth
rinse group. CONCLUSION: Green tea mouth rinse can be a promising preventive
therapy worldwide for the prevention of dental caries.
PMID- 28492195
TI - Evaluation of nitrous oxide-oxygen and triclofos sodium as conscious sedative
agents.
AB - BACKGROUND: Conscious sedation is used in the pediatric dentistry to reduce fear
and anxiety in children and promote favorable treatment outcomes. To achieve
them, the primary clinical need is for a well-tolerated, effective, and expedient
analgesic and sedative agent that is safe to use. AIM: The aim of the present
study was to evaluate the efficacy of nitrous oxide-oxygen and triclofos sodium
as conscious sedative agents in 5-10-year-old children. METHODOLOGY: Sixty
children aged 5-10 years showing anxious, uncooperative, and apprehensive
behavior were randomly divided and assigned into two groups (Groups A and B) such
that Group A received 40% nitrous oxide-60% oxygen and Group B received triclofos
sodium in the dose of 70 mg/kg body weight, given 30 min before the treatment
procedure. During the whole course of sedation procedure, the response of the
child was assessed using Houpt's behavior rating scale. The acceptance of route
of drug administration by the patient and parent was also assessed. Data obtained
were statistically evaluated using the Mann-Whitney U-test and Chi-square test.
RESULTS: Children sedated with triclofos sodium were significantly more drowsy
and disoriented compared to those sedated with nitrous oxide. The overall
behavior of children in both the groups was similar. Good parental acceptance was
observed for both the routes of administration. Patients accepted the oral route
significantly better than inhalation route. CONCLUSION: Both nitrous oxide-oxygen
and triclofos sodium were observed to be effective sedative agents, for
successful and safe use in 5-10-year-old dental patients. Patients showed a good
acceptance of the oral route compared to the inhalation route for sedation.
PMID- 28492196
TI - Comparative evaluation of effect of use of toothbrush with paste and munident on
levels of Streptococcus mutans and gingival health in children: An in vivo study.
AB - AIM: Dental caries is a multifactorial disease which has a deleterious effect on
the oral cavity. Improper oral hygiene habits are a cause for the same. The aim
of this study was to compare the antibacterial efficacy of Munident, an Ayurvedic
(herbal) dentifrice with commercially available toothpaste. MATERIALS AND
METHODS: A total of forty subjects between the age group 9 and 12 years, resident
of Bala Yeshu Nilaya Bhavan, Mangalore, Karnataka, India, were chosen for our
study. They were divided into two groups containing twenty subjects in each;
Group 1 for standard toothpaste and Group 2 for Munident. The decayed, missing,
and filled teeth scores were noted from each subject. Group 1 was instructed to
brush the teeth using commercially available toothpaste and Group 2 was
instructed to brush using commercially available Munident (herbal) dentifrice.
Both the groups brushed the teeth using soft variety of tooth brush. The gingival
bleeding index and salivary Streptococcus mutans count were noted pre- and post
brushimg for both groups. The results obtained were subjected to statistical
analysis. RESULTS: Munident (herbal) dentifrice showed better efficacy in
comparison to toothpaste in terms of gingival bleeding index and salivary S.
mutans count. CONCLUSION: Munident (herbal) dentifrice has better gingival
bleeding index compared to standard formulation of toothpaste. Hence, the
practice of using herbal dentifrice should be encouraged.
PMID- 28492197
TI - The effect of atraumatic restorative treatment on adhesive restorations for
dental caries in deciduous molars.
AB - BACKGROUND: Minimal invasive approaches to managing caries, such as partial
caries removal techniques and atraumatic restorative treatment (ART), are showing
increasing evidence of improved outcomes over the conventional complete caries
removal. OBJECTIVE: To evaluate clinically and radiographically the effect of ART
on restorations using restorative cement and glass ionomer cement (GIC) for
dental caries in the deciduous molars of children aged between 4 and 8 years.
SETTINGS AND DESIGN: The study design was a split-mouth, randomized, blind
clinical trial. MATERIALS AND METHODS: Eighty-six patients had 108 restorations
placed with GIC (Ketac Molar Easy Mix - 3M ESPE) and 108 restorations placed with
composite resin (CR) (Filtek Z250 - 3M ESPE). The restorations were assessed by
means of images obtained with a digital camera and periapical radiographs at
baseline and after 12 months of follow-up. STATISTICAL ANALYSIS: The Student's t
test, Pearson Chi-squared test, and Bonferroni paired comparison test were used
to evaluate the differences in proportions and correlations between the
variables. RESULTS: After 12 months of follow-up, the restorations were
considered clinically successful in 89.3% of cases and radiographically
successful in 80.5% of cases. There was statistical difference neither between
the two restorative materials used nor between the numbers of restored surfaces.
CONCLUSIONS: GIC and CR can be used successfully for restorations of one or two
dental surfaces after ART.
PMID- 28492199
TI - An infant case of intraoral penetrating injury with a toothbrush causing
retropharyngeal and upper mediastinal emphysema.
AB - A 2-year-old male child who was running and fell with a toothbrush in his mouth
suffered an injury to the inside of his right cheeks. His mother noticed that the
toothbrush had impaled his mouth, and removed it. On arrival, a wound was
observed on the right cheeks and palate. His general condition was good. However,
computed tomography revealed emphysema from the left side of epipharynx to the
upper mediastinum. This patient shows the importance of not only checking the
medical history and performing a physical examination but also performing an
imaging examination.
PMID- 28492198
TI - Comparison of efficacy of three chemotherapeutic agents on Streptococcus mutans
count in plaque and saliva: A randomized controlled triple blind study.
AB - BACKGROUND: There is a need for exploration of the role of chemotherapeutic
agents and its role in the prevention of early childhood caries (ECC) and its
recurrence. AIM: The aim of this study was two-fold: (1) To compare the
antimicrobial efficacy of three commonly used chemotherapeutic agents in the
prevention of ECC in comparison with a control and (2) To ascertain the role of
chemotherapeutic agents in the prevention of ECC. MATERIALS AND METHODS: Sixty
children with ECC in the age group 3-6 years were randomly allocated into four
groups. To each group of children after full oral rehabilitation either 10%
povidone-iodine (PI), or chlorhexidine (CHX) varnish (Cervitec Plus), or fluoride
varnish (Fluor Protector) were applied twice at an interval of 1 week, Group 4
served as control. Streptococcus mutans count in saliva and plaque were collected
at baseline, 30, 60, and 90 days and the presence of S. mutans was evaluated
using the Dentocult SM strip mutans kit. The efficacy of 10% PI, CHX varnish
(Cervitec Plus), and fluoride varnish (Fluor Protector) was compared with the
control group at 30, 60, and 90 days. An intergroup comparison was also done
during the same time intervals. RESULTS: The reduction of S. mutans count in the
plaque and saliva was greatest in the fluoride varnish treated groups at all time
intervals (30, 60, and 90 days). Fluoride varnish, CHX varnish, and 10% PI showed
significant improved efficacy when compared to the control group (P < 0.001).
Fluoride varnish showed significantly lower counts of S. mutans compared to CHX
varnish at all time intervals (30, 60, and 90 days) and also significantly lower
counts compared to 10% PI at 60 and 90 days interval (P < 0.001).
PMID- 28492200
TI - Anesthesia-related mortality in pediatric patients in dental office setting.
PMID- 28492201
TI - Erratum: Determination of toral antioxidant capacity of saliva in sickle cell
anemic patients - A cross-sectional study.
AB - [This corrects the article DOI: 10.4103/0970-4388.199219].
PMID- 28492202
TI - Spirometric evaluation of ventilatory function in adult male cigarette smokers in
Sokoto metropolis.
AB - BACKGROUND: Cigarette smoking is a widespread social habit in Nigeria with
extensive deleterious multisystemic effect. Ventilatory dysfunction is one of the
cigarette smoking-related illnesses that affect the respiratory system.
Spirometry is an investigative method that can be used for the early detection of
ventilatory dysfunction even before the onset of the symptoms. SUBJECTS AND
METHODS: A questionnaire adapted from the European Community Respiratory Health
Survey was administered to collect demographic, clinical, and cigarette smoking
data. Ventilatory function test was conducted using Clement Clarke (One Flow)
Spirometer, version 1.3. The highest value of each ventilatory function index was
chosen for analysis, and individual(s) with ventilatory dysfunction were
subjected to post bronchodilator spirometry. RESULTS: For the purpose of this
research, 150 participants who were currently cigarette smokers were enrolled,
and 50 apparently healthy, age-matched individuals who were never smokers served
as controls in the ratio of 3:1. Eighty percent of participants and 68% of
controls were aged 40 years or below. The mean age of participants (34.27 +/-
8.91 years) and the controls (35.08 +/- 10.35 years) was not significantly
different (P = 0.592). Similarly, there were no statistically significant
differences between the mean anthropometric indices (weight: P = 0.663, height: P
= 0.084, and body mass index: P = 0.099) of both participants and controls. The
mean values of FEV1 (forced expiratory flow in one second) and FEV1/FVC
(FVC=forced vital capacity) were lower in the participants compared to the
controls, and this difference was statistically significant (P < 0.001). There
was a weak negative correlation between pack-years of cigarette smoking and FEV1
(r = -0.237 and P = 0.004). Obstructive ventilatory defect was found among six
study participants (4%) and two controls (4%). CONCLUSION: Cigarette smoking is
associated with decline in ventilatory function test indices (FEV1 and FEV1/FVC)
in adult males. Decline in FEV1 is directly related to pack-years of cigarette
smoking.
PMID- 28492203
TI - Assessment of tobacco control efforts in three Sub-Saharan African countries.
AB - BACKGROUND: Tobacco industry's undermining of tobacco control goes on unabated in
sub-Saharan African countries, especially in Kenya, Nigeria, and Uganda. The
Framework Convention on Tobacco Control (FCTC) contains provisions aimed at
curbing these activities. However, the level to which FCTC is implemented and the
strength of each country's tobacco control law will determine its usefulness in
this regard. We determined the implementation status and strength of tobacco
control laws in Kenya, Nigeria, and Uganda. MATERIALS AND METHODS: The World
Health Organization and Campaign for Tobacco-Free Kids websites were queried for
secondary data related to tobacco control. Sources and data were disambiguated
and reported as tables. Composite scores for implementation were computed based
on the number of indicators of the articles of the FCTC reported on by each
country. Strength of tobacco control law (SoTCL) was computed based on the total
number of domains of the laws meeting a defined acceptable standard. Total
obtainable score for implementation and SoTCL were 148 and 38, respectively.
RESULTS: On the FCTC, Kenya, Nigeria, and Uganda achieved 75, 61.5, and 46.6%
implementation, respectively. SoTCL was weakest in the smoke-free domain for
Kenya, tobacco advertisement promotion and sponsorship domain for Nigeria, and
packaging and labeling domain for Uganda. SoTCL scores were 18 (47.4%), 20
(52.6%), and 34 (89.5%) for Nigeria, Kenya, and Uganda, respectively. CONCLUSION:
Kenya, Nigeria, and Uganda will need to strengthen their tobacco control laws
through appropriate amendment as well as regulatory mechanisms that guarantee
alignment with FCTC and the implementation thereof.
PMID- 28492204
TI - Impact assessment study after 27 years of community-directed treatment with
ivermectin in Galadimawa, Kaduna State, Nigeria.
AB - PURPOSE: To assess the impact on blindness after 27 years of community-directed
treatment with ivermectin (CDTI) in the Galadimawa community of Kauru Local
Government in Kaduna state, Nigeria. The population of Galadimawa constituted
about 12% of the total population examined during the ivermectin randomised
control trial (RCT) in 1989. The RCT population of 8000 individuals was scattered
over 36 villages in Kaduna state. Thus, longitudinal data are available on
blindness. MATERIALS AND METHODS: After 27 years of dosing with ivermectin, the
people in the community of Galadimawa were re-examined for the prevalence and
causes of blindness. This was achieved by an examination of the visually
disabled. The findings were compared with the situation in 1989 before the dosing
commenced. RESULTS: The population of the village increased from 711 to 1419. The
prevalence of blindness dropped from 4.9 to 0.96%. The most common causes of
blindness were now cataract (55.2%) and optic atrophy (27.6%), whereas the most
common causes in 1989 were onchocerciasis (28.3%), glaucoma (17.4%) and cataract
(10.9%). People with optic atrophy were more likely to have taken fewer doses of
ivermectin over the years. The blind people encountered in 2016 were on average
17 years older than those seen in 1989, which suggests that blindness, when it
occurs, is delayed by almost two decades. CONCLUSION: CDTI has reduced the
prevalence of blindness significantly in Galadimawa and may reflect the situation
elsewhere in the Kaduna state, which is an oncho-endemic zone.
PMID- 28492205
TI - The identification and grading of the psychosocial impact of Tinea capitis in
primary school children in a semi-urban area of Rivers State, Nigeria.
AB - INTRODUCTION: Tinea capitis is a fungal skin disease, which is not life
threatening but could affect the psychosocial life of those suffering from it.
Thus, this study sought to identify and grade the psychosocial impact related to
Tinea capitis in primary school children. SUBJECTS AND METHODS: This was a cross
sectional study involving primary school children in Emohua Local Government Area
of Rivers State. These children had been clinically diagnosed with Tinea capitis.
The Children Dermatology Life Quality Index instrument was used to identify the
presence of a psychosocial impact, which was graded as none, mild, moderate, and
severe. The Statistical Package for Social Sciences version 20 software was used
for analysis, and statistical significance was set at P < 0.05. RESULTS: A total
of 184 children aged 6-12 years with Tinea capitis participated in the study. The
mean age of the children was 9.5 +/- 2.9 years. The male-to-female ratio was
2.5:1. More than half of the children (58.2%, n = 127) had mild-to-severe
psychosocial impact. The psychosocial impact was significantly higher (P = 0.02)
among the female children (61.5%; n = 32) than the male children (41.7%; n = 20).
In addition, female children with Tinea capitis were 2.2 times more likely to
suffer a psychosocial impact than their male counterparts (odds ratio = 2.2; 95%
confidence interval: 1.16-4.32). There were no significant differences in the
psychosocial impact across the age categories (P = 0.859). CONCLUSION: Tinea
capitis has a psychosocial impact on the daily lives of school children, with
more than half of the children experiencing mild-to-severe grades of psychosocial
impact. Collaboration between mental health physicians and pediatric
dermatologists is encouraged to address the effect of Tinea capitis on the
psychosocial life of school children, especially the female children.
PMID- 28492206
TI - Community screening for pre-hypertension, traditional risk factors and markers of
chronic kidney disease in Ondo State, South-Western Nigeria.
AB - BACKGROUND: Chronic kidney disease (CKD) has become an epidemic with many
recognised risk factors. However, the role of pre-hypertension in CKD is yet to
be fully studied in our environment. OBJECTIVES: We set out to determine the
magnitude of pre-hypertension and traditional CKD risk factors. We also
determined their relationships to proteinuria. SUBJECTS AND METHODS: This was a
descriptive, cross-sectional study conducted in two urban local government areas
(Akure South and Ondo West) in Ondo State, Southwest Nigeria in March 2014. A
total of 1,183 adults (M:F, 0.63:1) were studied. Their bio-data, history of
cigarette smoking, alcohol intake, herbal usage, non-steroidal anti-inflammatory
drugs (NSAIDs), diabetes and hypertension were obtained. A total of 1,183 adults
(M:F, 0.63:1) blood pressure (BP) and anthropometry were determined. Urinalysis
was conducted using Combi-Uriscreen(r) 10SL. Data were analysed using the
Statistical Package for the Social Sciences version 20.0. RESULTS: A total of
1183 adults (M:F, 1:1.6) were studied with a mean age of 44.7 +/- 17.4 years.
Their mean systolic BP, diastolic BP and body mass index were 129.6 +/- 23.7
mmHg, 79.8 +/- 14 mmHg and 26.2 +/- 5.8 kg/m2, respectively. Pre-hypertension was
present in 32.3% of the subjects, while hypertension was present in 43.4% of the
subjects; 6.2% gave history of diabetes, 4.5% smoked cigarette, 68.3% used herbs
and 44.1% used NSAIDs. Proteinuria was present in 25.9% of the subjects, while
haematuria was present in 1.7% of the subjects. BP and age showed significant
association to proteinuria. CONCLUSION: Pre-hypertension and known risk factors
of CKD are prevalent in the people of Ondo State, Nigeria. Individuals with
persistent pre-hypertension should be routinely screened for CKD and referred to
the Nephrologist for early intervention.
PMID- 28492207
TI - Research experience of resident doctors who attended research methodology courses
of the National Postgraduate Medical College of Nigeria.
AB - INTRODUCTION: For over three decades, the National Postgraduate Medical College
of Nigeria (NPMCN) has been vested with the responsibility of overseeing
postgraduate medical training. The main objective of this study was to assess the
residents' perception of research as well as challenges faced in pursing seamless
research during their training. MATERIALS AND METHODS: This study was a cross
sectional descriptive survey in 2013. Self-administered questionnaires were
distributed to the participants of the annual research methodology workshop in
all the 15 faculties of the NPMCN. The questionnaires assessed the residents'
previous exposure to research, their publication history and their trainers'
input to their own research. Statistical analysis was performed using the
Statistical Package for the Social Sciences version 20 software. RESULTS: Four
hundred and one resident doctors, out of a total of 415 who attended the course,
completed the questionnaires during the study period (96.6% response rate). There
were 269 (67.0%) males and 132 (33.0%) females, giving a male-to-female ratio of
2:1. About three-quarters of them admitted that their exposure to research during
training was grossly inadequate. Twenty-five percent of them were involved in a
previous research before residency training, and a further 70% of respondents
were involved in their trainers' research work. Ninety-four percent in our study
identified a lack of dedicated time to be spared for research as a major obstacle
to research. CONCLUSION: Contribution and exposure to research among postgraduate
trainees in Nigeria are low. Lack of dedicated time for research was viewed as
the major obstacle to research by most residents.
PMID- 28492208
TI - Self-reported dental pain and dental caries among 8-12-year-old school children:
An exploratory survey in Lagos, Nigeria.
AB - BACKGROUND: Dental pain is considered an important public health problem because
it affects the daily life of children. This study was designed to assess the
prevalence, associated factors, and impact of dental pain among 8-12-year-old
school children in Lagos, Nigeria. SUBJECTS AND METHODS: A cross-sectional survey
to determine self-reported dental pain among 8-12-year-old school children using
an interviewer-administered questionnaire was conducted. This was followed by a
clinical examination to determine the child's oral hygiene status and dental
caries status. Chi-square and Fisher's exact tests were used for comparing
proportions. Binary logistic regression analysis was also conducted. Statistical
significance was set at P < 0.05. RESULTS: Of the 414 children included in the
survey, 254 (61.4%) children and 103 (24.9%) children reported experiencing
dental pain 3 months and 4 weeks before the survey, respectively. Caries
prevalence was 21.0%, whereas mean decayed, missing, and filled tooth index score
was 0.4420 (+/-1.078). A report of pain up to 3 months before the survey was
significantly associated with the child's age [odds ratio (OR) = 1.254;
confidence interval (CI) = 1.037-1.516; P = 0.019], whereas the type of school
attended (OR = 1.786; CI = 1.124-2.840; P = 0.014) and the presence of dental
caries (OR = 1.738; CI = 1.023-2.953; P = 0.041) were significantly associated
with reporting pain 4 weeks before the survey. CONCLUSION: The prevalence of self
reported dental pain was high among the children surveyed. Report of dental pain
was associated with the presence of dental caries. The provision of school oral
health services could be useful in reducing the level of untreated caries and
possibly dental pain among school children.
PMID- 28492209
TI - Some characteristics of gliomas managed at a Neurosurgery centre in Nigeria.
AB - BACKGROUND: Gliomas are important primary brain tumours with varying prognosis.
AIM: To study the histology characteristics of brain gliomas managed in a
Neurosurgical centre in Nigeria. MATERIALS AND METHODS: A retrospective analysis
of prospectively recorded data of patients managed for intracranial gliomas at
our Hospital for Neurosurgery, between year 2006 and 2015. Only the patients with
conclusive histology diagnosis following surgery were analysed. RESULTS: Glioma
was 23.8% of the 252 histology-confirmed brain tumours. Male-to-female ratio was
1.4:1.0. Peak age at diagnosis was in the fifth decade of life. There was an
increase in the frequency of diagnosis from seven (2006-2009) to 15 (2011 and
2012) and 39 patients managed (2013 and 2015). In sub-group analysis, grade IV
tumour was the most common (34.6%) followed by grade II (30.7%), grade I (18.3%)
and grade III (16.7%). Seven patients of grade II oligodendroglioma and one
patient each of anaplastic oligodendroglioma, subependymal giant cell astrocytoma
and astroblastoma were seen. The anatomical location of the tumour was the
frontal lobe in 23.3% of patients followed by the parietal lobe in 16.7% of
patients. The pre-operative Karnofsky score was >=70% in 36.7% of the patients.
CONCLUSION: Gliomas are more common brain tumours than were imagined. Most
patients present relatively late and with advanced disease. High-grade gliomas
seem to mostly affect the middle age population in the study environment with
higher proportion of grade IV lesions.
PMID- 28492210
TI - Predictors of quality of life in patients with diabetes mellitus in two tertiary
health institutions in Ghana and Nigeria.
AB - BACKGROUND: Patients with chronic diseases such as Type 2 diabetes mellitus (DM)
usually have a relatively poor quality of life (QoL), because the cost of care
(living expenses and health) or diet restrictions are heavily felt by these
patients, and this is of a public health concern. However, limited data on DM QoL
exist in Ghana and Nigeria. This makes it imperative for data to be collated in
that regard. MATERIALS AND METHODS: We adopted the Strengthening The reporting of
observational studies in epidemiology (STROBE) consensus checklist to survey the
patients with DM seen at the diabetic clinic at the Department of Medicine of the
Korle-Bu Teaching Hospital and University College Hospital, Ibadan, Nigeria.
Patients with Type 2 DM aged 40 years and older were recruited by using
systematic random sampling method. The World Health Organization Quality of Life
BREF, diabetes empowerment scale, and DM knowledge scale were used to assess QoL,
patient empowerment, and knowledge of DM, respectively. The predictors of QoL
were determined using multiple linear regression analyses. RESULTS: A total of
198 patients in Ghana and 203 patients in Nigeria completed the survey, with
female-to-male ratio being 3:1 and 2:1, respectively. The overall QoL in both
countries was relatively low: 56.19 +/- 8.23 in Ghana and 64.34 +/- 7.34 in
Nigeria. In Ghana, significant correlates of higher scores on the QoL scale were
medication adherence (P = 0.02) and employment status (P = 0.02). Among patients
in Nigeria, employment status (P = 0.02) and DM empowerment (0.03) were
significant predictors of QoL in patients with DM. CONCLUSION: Our study revealed
an association between a number of psychosocial factors and QoL among patients
with DM in Ghana and Nigeria.
PMID- 28492212
TI - Isolated sternal cleft in a patient with atrial septal defect: A rare sole
association.
AB - Sternal cleft (SC) is a rare form of chest wall deformity with an incidence of
<0.15%. It occurs because of failure of fusion of the sternal bars about the 7
9th week of intrauterine life. It could occur in isolation or as a part of a
syndromic complex. This condition exposes the vital mediastinal structures to a
huge risk of injury, aside from cosmetic issues. Treatment in the neonatal period
is most favourable, though other modalities are available in the later stages of
life, but it can be challenging. We present the case of a 2-month-old female
infant with a superior SC with a single association of secundum atrial septal
defect. She was asymptomatic. She was treated by primary repair to protect the
underlying mediastinal structures as well as for cosmetic reasons. Such a repair
resulted in good clinical outcome.
PMID- 28492211
TI - Raised adenosine deaminase in the cerebrospinal fluid: A tool for the diagnosis
of tuberculous meningitis in developing countries.
AB - CONTEXT: The rapid diagnosis followed by the early treatment of tuberculous
meningitis (TBM) is important in preventing fatal outcomes. The mainstay of
diagnosis lies in cerebrospinal fluid (CSF) analysis, radiological
investigations, and clinical findings. AIM: The present study was conducted to
determine the efficacy, sensitivity, and specificity of raised adenosine
deaminase (ADA) level in CSF to differentiate TBM from non-TBM cases as a rapid,
cost-effective, and noninvasive test. PATIENTS AND METHODS: This was a
retrospective study conducted over a 1-year period in a tertiary teaching
institute of Malwa region, India. A total of 143 patients presented with symptoms
and signs of meningitis were included and divided into TBM and non-TBM groups on
the basis of the diagnostic criteria. CSF ADA estimation was drafted and analyzed
by using >=10 U/L as a cutoff value. A statistical comparison of the ADA levels
between the study groups was made by using unpaired Student's t-test. RESULTS:
Out of the 143 cases, 40 were TBM, and 103 were non-TBM. The mean ADA level in
TBM and non-TBM cases was 17.18 +/- 9.59 and 6.33 +/- 2.48, respectively, and the
difference was statistically significant. Using a cutoff level >=10 U/L, CSF ADA
had a sensitivity of 92.5% and a specificity of 89.32%. Positive and negative
likelihood ratios of the test were 8.66 and 0.08, respectively, and positive and
negative predictive values, were 77.08 and 96.84%, respectively. CONCLUSION: The
present study reflects the importance of a CSF ADA level >=10 U/L in the
diagnosis of TBM. Thus, it can be used as an adjunctive diagnostic tool to
differentiate TBM from other non-TBM cases, when there is a diagnostic dilemma.
PMID- 28492213
TI - Psychiatry outside the framework of empiricism.
AB - Science is interested in whatever that is empirical and objective. Any claim that
cannot be objectively demonstrated has no place in science, because the subject
does not deviate from the role, which it has set out to play in the life of
mankind. Psychiatry, as a scientific discipline, plays along these basic
principles. In the etiology, symptomatology, and management of psychiatric
disorders, the biopsychosocial model recognizes the role of biological,
psychological, and social factors. This essay views psychiatry from the
biopsychosocial perspective and asserts that certain elements, which may not be
readily and empirically verifiable, are important in the practice of psychiatry.
PMID- 28492214
TI - The Faculty of Health Studies at the University of Mostar in the Service of
Health.
AB - The continuous progress of science has a very positive effect on health care.
Health care in its broader sense has greatly progressed in past decades, and the
education of health care professions requires more continuous learning, teaching
materials and course duration. It becomes clear that continuous education is not
only important for good quality doctors, but all participants of health care are
gaining more burdens and their work becomes more complex. There is an increased
necessity for team work, division of tasks and specialization. In this battle for
health, the Faculty of Health Studies becomes a necessity and has an obligation
in education of various health personnel due to acquiring practical and
theoretical skills, as well as abilities in providing the best possible health
care. The path of knowledge is long and difficult. It has been present at our
faculty for 17 years and we carry it out through a variety of undergraduate and
graduate programs, and as of this years through our postgraduate program. Besides
the education of health care workers we wanted to offer to our current and former
students, and their educators the possibility of publishing their work, so in
2015 we launched our electronic journal, "Health Bulletin", whose publisher is
the Faculty of Health Studies. In the process of continuous battle for health,
prevention and treatment, the role of highly educated health care worker is of
increasing importance and he certainly becomes an indispensable link in this
process. The goal of our faculty is to educate the best possible health care
workers, who will in addition to high quality practical work gradually take over
our teaching responsibilities at the university.
PMID- 28492215
TI - Public Health Achievements and Challenges: Symposium of the University of Mostar
Faculty of Health Studies.
AB - Public health is an important area of health care that reflects the readiness of
the state and society to provide the welfare of all citizens through the
promotion of health and the preservation of a healthy environment - factors that
directly affect the health of the population. The field of public health is very
broad and its concept is changing over time, being defined in a narrower and
wider sense. In short, public health is a science and practice that aims at
ensuring the conditions in which people can preserve and improve their health and
prevent health damage. The third millennium brings its specifics, needs and
priorities according to challenges public health is faced by in the twenty-first
century: the economic crisis, rising inequality, population aging, rising rates
of chronic diseases, migration, urbanization, ecosystem change, climate change,
etc. The role of public health is to protect, improve health, prevent diseases
and injuries. Such a public health approach implies a multisectoral work focusing
on "wider health determinants", and within this activity experts from various
medical and non-medical profiles, whose field of public health is concerned, can
be found. The development of inter-departmental co-operation skills contributes
to a better understanding of health professionals and professionals of other
profiles, and facilitates common, synergistic actions in addressing public health
problems in the community. Symposium on Public Health Achievements and Challenges
organized by the University of Mostar Faculty of Health Studies is just another
indication of the obligation, the need and the desire for professional and
scientific contribution to the fight for better health. Our faculty has so far
organized other numerous symposia, and the aim of this symposium is to present
public health achievements and challenges in our surrounding in order to protect,
improve health, prevent diseases and injuries in a modern way.
PMID- 28492216
TI - Psychological Status and Quality of Life in Acne Patients Treated with Oral
Isotretinoin.
AB - INTRODUCTION: The acne patients are at higher risk of acquiring depresion and
anxiety, which can lead to reduced quality of life. Effective treatment of acne
can reduce symptoms of anxiety and depression and significantly improve other
physiological parameters and quality of life of these patients. The aim of this
study was to determine the psychological status and quality of life of acne
patients before, during and after the treatment with oral isotretinoin. SUBJECTS
AND METHODS: The prospective study included a total of 127 patients suffering
from moderate to severe form of acne. To assess the psychological status and
quality of life of studied groups the following standard psychometric
questionnaires were performed before, during and after the treatment with oral
isotretinoin: Beck Depression Inventory (BDI), Assessments of the Psychological
and Social Effects of Acne (APSEA), State Trait Anxiety Inventory (STAI), Measure
of Psychological Stress (MPS) and Dermatology Specific Quality of Life (DSQL).
RESULTS: Results of the present study indicate that there is no increase in
depressive and anxiety symptoms in the patients treated with oral isotretinoin.
The psychological status by gender has shown the existence of differences between
the genders in all measures of psychological status. Statistically significantly
better quality of life was observed after healing than before treatment.
CONCLUSION: The results of our study showed no higher risk of depression and
anxiety within the patients with acne treated with oral isotretinoin. Improvement
of quality of life after the treatment of acne with oral isotretinoin was
confirmed.
PMID- 28492217
TI - Prevalence of Intellectual Disabilities and Epilepsy in Different Forms of
Spastic Cerebral Palsy in Adults.
AB - BACKGROUND: Spastic cerebral palsy may be interconnected with other
neurodevelopmental disorders such as intellectual disabilities, and epilepsy.
Brain synaptic plasticity and successful restorative rehabilitation may also
contribute to diminish neurological deficit of patients having cerebral palsy.
The aim of this study was to investigate the prevalence of intellectual
disabilities and epilepsy in adult patients with different forms of spastic
cerebral palsy and to find out correlation between the severity level of
intellectual disabilities and epilepsy. SUBJECTS AND METHODS: Adults diagnosed
with different forms of spastic cerebral palsy were analyzed during a three-month
period. The investigated features were: gender and age; form of cerebral palsy;
the prevalence of intellectual disabilities and epilepsy. Intellectual
disabilities were divided into 4 severity levels. The correlation between the
severity level of intellectual disabilities and epilepsy was statistically
analyzed. RESULTS: Intellectual disability was present in 55% of patients
diagnosed with spastic cerebral palsy. Epilepsy was present in 36% of such
patients. It was recorded in 51.1% of quadriplegic, 21.9% of diplegic, and 19.2%
of hemiplegic patients. Intellectual disability was present in 73.8% of
quadriplegic, 31.3% of diplegic, and 53.8% of hemiplegic patients. The
statistically significant correlation existed between the severe intellectual
disability and epilepsy. CONCLUSIONS: Intellectual disabilities and epilepsy most
frequently occurred in patients with most severe forms of spastic cerebral palsy.
Epilepsy is strongly correlated to the severity level of intellectual disability.
Such patients require additional special modes of treatment and restorative
rehabilitation to improve the functional outcome.
PMID- 28492218
TI - The Impact of Religiosity on Quality of Life and Psychological Symptoms in
Chronic Mental Patients.
AB - INTRODUCTION: In recent decades, there is more and more scientific research and
evidence that religiosity has a positive impact on quality of life and mental
health. The aim this study is to evaluate the impact of religiosity on the
quality of life and psychological symptoms of chronic mental patients. SUBJECTS
AND METHODS: The test group was consisted of 100 chronic mental patients at the
Clinic for Psychiatry UCH Mostar, and control group was consisted of 80 somatic
patients surveyed from the Infirmary of family medicine of the Health Center
Mostar. The survey was conducted by the social and demographic questionnaire, a
questionnaire on the quality of life of the World Health Organization WHOQOL
BREF, the questionnaire on religiosity and self-assessment questionnaire for
psychological symptoms SCL-90th. RESULTS: For the socio-demographic data we
obtained results that chronic mental patients as opposed to chronic somatic
patients have significantly higher percent of an average lifestyle habits. There
is statistically significant difference in the place of residence, chronic mental
patients live in the city as opposed to somatic who live in the countryside. On
the question of religiosity we received information that the chronic mental
patients in relation to chronic somatic patients significantly more attend public
religious gatherings, but however, chronic somatic patients compared to chronic
mental significantly more use religiosity for better financial position, social
comfort. In self evaluation of psychological symptoms we received information
that the chronic mental patients as opposed to chronic somatic patients had
significantly more psychotic features. To test the quality of life between the
two groups, we received the information that chronic mental patients have
significantly better physical and mental health, social relationships and caring
for the environment as opposed to chronic somatic patients. CONCLUSIONS: Quality
of life was significantly better in the chronic mental patients. Also, chronic
mental patients significantly more attend public religious gatherings, while
chronic somatic patients significantly more use religiosity for a better
financial position, social comfort. Finally, chronic mental patients had a
significantly more pronounced psychotic features.
PMID- 28492219
TI - Kappa Free Light Chains in Cerebrospinal Fluid of Patients with Identified
Oligoclonal Immunoglobulin G.
AB - BACKGROUND: Production of kappa free light chains (KFLC) represents a part of
humoral immune response, along with the synthesis of intrathecal immunoglobulins.
Increased concentrations of immunoglobulin G light chains, kappa and lambda
chains, were identified through research of numerous diseases of central nervous
system. The qualitative method of isoelectric focusing (IEF) followed by
immunofixation currently represents the accepted standard in identifying
oligoclonal bands (OCB), but establishing a sensitive immunonephelometric method
for quantification of kappa free light chains (KFLC) in cerebrospinal fluid (CSF)
has paved a way for new diagnostic possibilities. Andersson classified the
pattern types of OCB, ranging from type 1 to type 5, wherein types 2 and 3
indicate intrathecal synthesis. Our aim was to determine KFLC in CSF of patients
with clinically isolated syndrome (CIS) who had presented with type 2 and type 3
OCB, to determine if there is a difference in concentrations between those two
groups and to establish a borderline value of KFLC which would enable
differential diagnostics. SUBJECTS AND METHODS: 70 patients, who underwent lumbar
punction for CSF analysis and had their blood sampled through the cubital vein,
participated in the study. Patients were classified according to Andersson as
type 2 or type 3, which besides adulthood, represented the inclusion criteria.
The average age of patients classified as type 2 was 36 years, and those
classified as type 3 was 39 years, where it is evident that there was not a
statistically significant difference (p=0.0685). We used a qualitative
electrophoretic technique of IEF with agarose gel followed by immunofixation, and
a quantitative immunonephelometric method. All results were interpreted on a
level of statistic significance of p<0.05. RESULTS: CSF KFLC concentrations in
type 3 were statistically and significantly elevated with regard to type 2 (Mann
Whitney test, p=0.0430). The median for KFLC in type 2 was 0.9 mg/L, while the
median for KFLC in type 3 was 2.71 mg/L, and the detection limit for both types
was 0.18 mg/L. We used a statistical ROC curve to determine that KFLC
concentration can be used for differential diagnostics, meaning it can
discriminate type 2 from type 3 with clinical sensitivity of 61% and clinical
specificity of 71% (AUC=0.641) (p=0.037). CONCLUSION: Despite the obtained
statistically significant differences in concentrations of KFLC between types of
OCBs and ROC analysis results, determination of KFLC by a nephelometric method,
insufficiently strong clinical sensitivity and specificity does not justify
abandonment of IEF method followed by immunofixation.
PMID- 28492220
TI - Family Atmosphere and Relationships as Predictors of Heroin Addiction.
AB - INTRODUCTION: Studies show that dysfunctional family relationships are important
predictors of addictions to all psychoactive substances. OBJECTIVE: To establish
if there is a connection between family relations and heroin addiction and if
found to exist, what is the quality of this connection. SUBJECTS AND METHODS:
This research was conducted on the sample comprised of 160 subjects divided into
two groups. The first group consisted of 61 heroin addicts treated at the Tuzla
University Clinical Centre Psychiatric Hospital. The second group consisted of 99
subjects who were students at the Tuzla University Faculties of Philosophy and
Electrical Engineering and who were not using any psychoactive substances. The
subjects were tested with the Quality of Family Interactions Scale (KOBI) which
measures the interactions between children and parents in two dimensions,
described in literature as 'acceptance' and 'rejection'. RESULTS: The research
team established statistically significant differences between the heroin addicts
and the students, the non-users, in terms of their family relationships. The
results show that the addicts families were characterized by lack of
understanding, by conflicts, rejection, non-acceptance by parents, while the non
users families were characterized by understanding, acceptance by parents and
good communication. CONCLUSIONS: There is a connection between inter-family
relationships and addiction. Namely, rejection and non-acceptance of
children/persons by their families and parents, bad communication and
dysfunctional family relationships are significant predictors of heroin
addiction.
PMID- 28492221
TI - Accuracy of Modified Alvarado Score, Eskelinen Score and Ohmann Score in
Diagnosing Acute Appendicitis.
AB - INTRODUCTION: By processing the data of a large number of patients with abdominal
pain, diagnostic scores whose implementation attempts to facilitate acute
appendicitis diagnostics were developed. Modified Alvarado score, Ohmann score
and Eskelinen score are used as assistance when setting the diagnosis and making
a decision to undertake surgery. AIM: To assess accuracy of Alvarado score,
Ohmann score and Eskelinen score in diagnosing acute appendicitis and to
establish connection of total score of these scoring systems with
histopathological degree of appendicitis. SUBJECTS AND METHODS: A cross-sectional
study was conducted at the Department of Surgery of University Clinical Hospital
Mostar. The study included 70 patients who underwent appendectomy and were scored
before surgery. All tested persons were examined by experienced surgeon who took
anamnesis, physical status and ordered laboratory diagnostic tests. Appendicitis
was excluded or confirmed by means of histopathological diagnostics, and the
degree of appendicitis was determined. RESULTS: According to accuracy parameters
(sensitivity, specificity, negative and positive predictive value), the score
which was of highest value was Ohmann score, followed by Eskelinen score, while
the lowest value was the one of modified Alvarado score. Total score in all three
scoring systems follows the degree of appendicitis, but statistical significance
was proven only for Ohmann and Eskelinen scores. CONCLUSION: Ohmann and Eskelinen
scores can be useful in diagnosing acute appendicitis, predicting the degree of
appendicitis, as well as assistance when making decision to undertake an
operative procedure. Modified Alvarado score in our subjects did not prove
sufficient value. Diagnostics of acute appendicitis still must be led by
contemporary algorithms in which diagnostic scoring is implemented.
PMID- 28492222
TI - A case report of a long time unrecognized hypochondriac patient wondering through
the hospital departments.
PMID- 28492223
TI - Scabies Mimicing Child Abuse - a Case Report.
PMID- 28492224
TI - Endogenous adenosine maintains cartilage homeostasis and exogenous adenosine
inhibits osteoarthritis progression.
AB - Osteoarthritis (OA) is characterized by cartilage destruction and chondrocytes
have a central role in this process. With age and inflammation chondrocytes have
reduced capacity to synthesize and maintain ATP, a molecule important for
cartilage homeostasis. Here we show that concentrations of ATP and adenosine, its
metabolite, fall after treatment of mouse chondrocytes and rat tibia explants
with IL-1beta, an inflammatory mediator thought to participate in OA
pathogenesis. Mice lacking A2A adenosine receptor (A2AR) or ecto-5'nucleotidase
(an enzyme that converts extracellular AMP to adenosine) develop spontaneous OA
and chondrocytes lacking A2AR develop an 'OA phenotype' with increased expression
of Mmp13 and Col10a1. Adenosine replacement by intra-articular injection of
liposomal suspensions containing adenosine prevents development of OA in rats.
These results support the hypothesis that maintaining extracellular adenosine
levels is an important homeostatic mechanism, loss of which contributes to the
development of OA; targeting adenosine A2A receptors might treat or prevent OA.
PMID- 28492225
TI - High-efficiency and high-power rechargeable lithium-sulfur dioxide batteries
exploiting conventional carbonate-based electrolytes.
AB - Shedding new light on conventional batteries sometimes inspires a chemistry
adoptable for rechargeable batteries. Recently, the primary lithium-sulfur
dioxide battery, which offers a high energy density and long shelf-life, is
successfully renewed as a promising rechargeable system exhibiting small
polarization and good reversibility. Here, we demonstrate for the first time that
reversible operation of the lithium-sulfur dioxide battery is also possible by
exploiting conventional carbonate-based electrolytes. Theoretical and
experimental studies reveal that the sulfur dioxide electrochemistry is highly
stable in carbonate-based electrolytes, enabling the reversible formation of
lithium dithionite. The use of the carbonate-based electrolyte leads to a
remarkable enhancement of power and reversibility; furthermore, the optimized
lithium-sulfur dioxide battery with catalysts achieves outstanding cycle
stability for over 450 cycles with 0.2 V polarization. This study highlights the
potential promise of lithium-sulfur dioxide chemistry along with the viability of
conventional carbonate-based electrolytes in metal-gas rechargeable systems.
PMID- 28492226
TI - Circulating tumour DNA sequence analysis as an alternative to multiple myeloma
bone marrow aspirates.
AB - The requirement for bone-marrow aspirates for genomic profiling of multiple
myeloma poses an obstacle to enrolment and retention of patients in clinical
trials. We evaluated whether circulating cell-free DNA (cfDNA) analysis is
comparable to molecular profiling of myeloma using bone-marrow tumour cells. We
report here a hybrid-capture-based Liquid Biopsy Sequencing (LB-Seq) method used
to sequence all protein-coding exons of KRAS, NRAS, BRAF, EGFR and PIK3CA in 64
cfDNA specimens from 53 myeloma patients to >20,000 * median coverage. This
method includes a variant filtering algorithm that enables detection of tumour
derived fragments present in cfDNA at allele frequencies as low as 0.25% (median
3.2%, range 0.25-46%). Using LB-Seq analysis of 48 cfDNA specimens with matched
bone-marrow data, we detect 49/51 likely somatic mutations, with subclonal
hierarchies reflecting tumour profiling (96% concordance), and four additional
mutations likely missed by bone-marrow testing (>98% specificity). Overall, LB
Seq is a high fidelity adjunct to genetic profiling of bone-marrow in multiple
myeloma.
PMID- 28492229
TI - Imaging of pH in vivo using hyperpolarized 13C-labelled zymonic acid.
AB - Natural pH regulatory mechanisms can be overruled during several pathologies such
as cancer, inflammation and ischaemia, leading to local pH changes in the human
body. Here we demonstrate that 13C-labelled zymonic acid (ZA) can be used as
hyperpolarized magnetic resonance pH imaging sensor. ZA is synthesized from [1
13C]pyruvic acid and its 13C resonance frequencies shift up to 3.0 p.p.m. per pH
unit in the physiological pH range. The long lifetime of the hyperpolarized
signal enhancement enables monitoring of pH, independent of concentration,
temperature, ionic strength and protein concentration. We show in vivo pH maps
within rat kidneys and subcutaneously inoculated tumours derived from a mammary
adenocarcinoma cell line and characterize ZA as non-toxic compound predominantly
present in the extracellular space. We suggest that ZA represents a reliable and
non-invasive extracellular imaging sensor to localize and quantify pH, with the
potential to improve understanding, diagnosis and therapy of diseases
characterized by aberrant acid-base balance.
PMID- 28492228
TI - Association between a common immunoglobulin heavy chain allele and rheumatic
heart disease risk in Oceania.
AB - The indigenous populations of the South Pacific experience a high burden of
rheumatic heart disease (RHD). Here we report a genome-wide association study
(GWAS) of RHD susceptibility in 2,852 individuals recruited in eight Oceanian
countries. Stratifying by ancestry, we analysed genotyped and imputed variants in
Melanesians (607 cases and 1,229 controls) before follow-up of suggestive loci in
three further ancestral groups: Polynesians, South Asians and Mixed or other
populations (totalling 399 cases and 617 controls). We identify a novel
susceptibility signal in the immunoglobulin heavy chain (IGH) locus centring on a
haplotype of nonsynonymous variants in the IGHV4-61 gene segment corresponding to
the IGHV4-61*02 allele. We show each copy of IGHV4-61*02 is associated with a 1.4
fold increase in the risk of RHD (odds ratio 1.43, 95% confidence intervals 1.27
1.61, P=4.1 * 10-9). These findings provide new insight into the role of germline
variation in the IGH locus in disease susceptibility.
PMID- 28492230
TI - Targeting the deubiquitinase STAMBP inhibits NALP7 inflammasome activity.
AB - Inflammasomes regulate innate immune responses by facilitating maturation of
inflammatory cytokines, interleukin (IL)-1beta and IL-18. NACHT, LRR and PYD
domains-containing protein 7 (NALP7) is one inflammasome constituent, but little
is known about its cellular handling. Here we show a mechanism for NALP7 protein
stabilization and activation of the inflammasome by Toll-like receptor (TLR)
agonism with bacterial lipopolysaccharide (LPS) and the synthetic acylated
lipopeptide Pam3CSK4. NALP7 is constitutively ubiquitinated and recruited to the
endolysosome for degradation. With TLR ligation, the deubiquitinase enzyme, STAM
binding protein (STAMBP) impedes NALP7 trafficking to lysosomes to increase NALP7
abundance. STAMBP deubiquitinates NALP7 and STAMBP knockdown abrogates LPS or
Pam3CSK4-induced increases in NALP7 protein. A small-molecule inhibitor of STAMBP
deubiquitinase activity, BC-1471, decreases NALP7 protein levels and suppresses
IL-1beta release after TLR agonism. These findings describe a unique pathway of
inflammasome regulation with the identification of STAMBP as a potential
therapeutic target to reduce pro-inflammatory stress.
PMID- 28492231
TI - PPKs mediate direct signal transfer from phytochrome photoreceptors to
transcription factor PIF3.
AB - Upon light-induced nuclear translocation, phytochrome (phy) sensory
photoreceptors interact with, and induce rapid phosphorylation and consequent
ubiquitin-mediated degradation of, transcription factors, called PIFs, thereby
regulating target gene expression and plant development. Nevertheless, the
biochemical mechanism of phy-induced PIF phosphorylation has remained ill
defined. Here we identify a family of nuclear protein kinases, designated
Photoregulatory Protein Kinases (PPK1-4; formerly called MUT9-Like Kinases
(MLKs)), that interact with PIF3 and phyB in a light-induced manner in vivo.
Genetic analyses demonstrate that the PPKs are collectively necessary for the
normal light-induced phosphorylation and degradation of PIF3. PPK1 directly
phosphorylates PIF3 in vitro, with a phosphosite pattern that strongly mimics the
light-induced pattern in vivo. These data establish that the PPKs are directly
involved in catalysing the photoactivated-phy-induced phosphorylation of PIF3 in
vivo, and thereby are critical components of a transcriptionally centred
signalling hub that pleiotropically regulates plant growth and development in
response to multiple signalling pathways.
PMID- 28492235
TI - Fast oxygen diffusion and iodide defects mediate oxygen-induced degradation of
perovskite solar cells.
AB - Methylammonium lead halide perovskites are attracting intense interest as
promising materials for next-generation solar cells, but serious issues related
to long-term stability need to be addressed. Perovskite films based on CH3NH3PbI3
undergo rapid degradation when exposed to oxygen and light. Here, we report
mechanistic insights into this oxygen-induced photodegradation from a range of
experimental and computational techniques. We find fast oxygen diffusion into
CH3NH3PbI3 films is accompanied by photo-induced formation of highly reactive
superoxide species. Perovskite films composed of small crystallites show higher
yields of superoxide and lower stability. Ab initio simulations indicate that
iodide vacancies are the preferred sites in mediating the photo-induced formation
of superoxide species from oxygen. Thin-film passivation with iodide salts is
shown to enhance film and device stability. The understanding of degradation
phenomena gained from this study is important for the future design and
optimization of stable perovskite solar cells.
PMID- 28492234
TI - Molecular basis for blue light-dependent phosphorylation of Arabidopsis
cryptochrome 2.
AB - Plant cryptochromes undergo blue light-dependent phosphorylation to regulate
their activity and abundance, but the protein kinases that phosphorylate plant
cryptochromes have remained unclear. Here we show that photoexcited Arabidopsis
cryptochrome 2 (CRY2) is phosphorylated in vivo on as many as 24 different
residues, including 7 major phosphoserines. We demonstrate that four closely
related Photoregulatory Protein Kinases (previously referred to as MUT9-like
kinases) interact with and phosphorylate photoexcited CRY2. Analyses of the
ppk123 and ppk124 triple mutants and amiR4k artificial microRNA-expressing lines
demonstrate that PPKs catalyse blue light-dependent CRY2 phosphorylation to both
activate and destabilize the photoreceptor. Phenotypic analyses of these mutant
lines indicate that PPKs may have additional substrates, including those involved
in the phytochrome signal transduction pathway. These results reveal a mechanism
underlying the co-action of cryptochromes and phytochromes to coordinate plant
growth and development in response to different wavelengths of solar radiation in
nature.
PMID- 28492232
TI - Pemphigus.
AB - Pemphigus is a group of IgG-mediated autoimmune diseases of stratified squamous
epithelia, such as the skin and oral mucosa, in which acantholysis (the loss of
cell adhesion) causes blisters and erosions. Pemphigus has three major subtypes:
pemphigus vulgaris, pemphigus foliaceus and paraneoplastic pemphigus. IgG
autoantibodies are characteristically raised against desmoglein 1 and desmoglein
3, which are cell-cell adhesion molecules found in desmosomes. The sites of
blister formation can be physiologically explained by the anti-desmoglein
autoantibody profile and tissue-specific expression pattern of desmoglein
isoforms. The pathophysiological roles of T cells and B cells have been
characterized in mouse models of pemphigus and patients, revealing insights into
the mechanisms of autoimmunity. Diagnosis is based on clinical manifestations and
confirmed with histological and immunochemical testing. The current first-line
treatment is systemic corticosteroids and adjuvant therapies, including
immunosuppressive agents, intravenous immunoglobulin and plasmapheresis.
Rituximab, a monoclonal antibody against CD20+ B cells, is a promising
therapeutic option that may soon become first-line therapy. Pemphigus is one of
the best-characterized human autoimmune diseases and provides an ideal paradigm
for both basic and clinical research, especially towards the development of
antigen-specific immune suppression treatments for autoimmune diseases.
PMID- 28492233
TI - ISCA1 is essential for mitochondrial Fe4S4 biogenesis in vivo.
AB - Mammalian A-type proteins, ISCA1 and ISCA2, are evolutionarily conserved proteins
involved in iron-sulfur cluster (Fe-S) biogenesis. Recently, it was shown that
ISCA1 and ISCA2 form a heterocomplex that is implicated in the maturation of
mitochondrial Fe4S4 proteins. Here we report that mouse ISCA1 and ISCA2 are Fe2S2
containing proteins that combine all features of Fe-S carrier proteins. We use
biochemical, spectroscopic and in vivo approaches to demonstrate that despite
forming a complex, ISCA1 and ISCA2 establish discrete interactions with
components of the late Fe-S machinery. Surprisingly, knockdown experiments in
mouse skeletal muscle and in primary cultures of neurons suggest that ISCA1, but
not ISCA2, is required for mitochondrial Fe4S4 proteins biogenesis. Collectively,
our data suggest that cellular processes with different requirements for ISCA1,
ISCA2 and ISCA1-ISCA2 complex seem to exist.
PMID- 28492236
TI - Kondo blockade due to quantum interference in single-molecule junctions.
AB - Molecular electronics offers unique scientific and technological possibilities,
resulting from both the nanometre scale of the devices and their reproducible
chemical complexity. Two fundamental yet different effects, with no classical
analogue, have been demonstrated experimentally in single-molecule junctions:
quantum interference due to competing electron transport pathways, and the Kondo
effect due to entanglement from strong electronic interactions. Here we unify
these phenomena, showing that transport through a spin-degenerate molecule can be
either enhanced or blocked by Kondo correlations, depending on molecular
structure, contacting geometry and applied gate voltages. An exact framework is
developed, in terms of which the quantum interference properties of interacting
molecular junctions can be systematically studied and understood. We prove that
an exact Kondo-mediated conductance node results from destructive interference in
exchange-cotunneling. Nonstandard temperature dependences and gate-tunable
conductance peaks/nodes are demonstrated for prototypical molecular junctions,
illustrating the intricate interplay of quantum effects beyond the single-orbital
paradigm.
PMID- 28492237
TI - Proline metabolism supports metastasis formation and could be inhibited to
selectively target metastasizing cancer cells.
AB - Metastases are the leading cause of mortality in patients with cancer. Metastasis
formation requires cancer cells to adapt their cellular phenotype. However, how
metabolism supports this adaptation of cancer cells is poorly defined. We use 2D
versus 3D cultivation to induce a shift in the cellular phenotype of breast
cancer cells. We discover that proline catabolism via proline dehydrogenase
(Prodh) supports growth of breast cancer cells in 3D culture. Subsequently, we
link proline catabolism to in vivo metastasis formation. In particular, we find
that PRODH expression and proline catabolism is increased in metastases compared
to primary breast cancers of patients and mice. Moreover, inhibiting Prodh is
sufficient to impair formation of lung metastases in the orthotopic 4T1 and
EMT6.5 mouse models, without adverse effects on healthy tissue and organ
function. In conclusion, we discover that Prodh is a potential drug target for
inhibiting metastasis formation.
PMID- 28492238
TI - Association of oxygen uptake at ventilatory threshold with risk of incident
hypertension: a long-term prospective cohort study.
PMID- 28492239
TI - Reductions in blood pressure during a community-based overweight and obesity
treatment in children and adolescents with prehypertension and hypertension.
AB - Due to the pandemic of childhood obesity and thus obesity-related hypertension,
improvements in treatment availability are needed. Hence, we investigated whether
reductions in blood pressure (BP) would occur in children with overweight and
obesity exhibiting prehypertension/hypertension during a community-based
overweight and obesity treatment program, and if changes in body mass index (BMI)
are associated with changes in BP. The study included 663 children aged 3-18
years with a BMI ?85th percentile for sex and age that entered treatment from
June 2012 to January 2015. Height, weight and BP were measured upon entry and
every 3-6 months. BMI and BP s.d. scores (SDSs) were calculated according to sex
and age, or sex, age and height. Prehypertension was defined as a BP SDS ?1.28
and <1.65. Hypertension was defined as a BP SDS ?1.65. Upon entry, 52% exhibited
prehypertension (11.9%) or exhibited hypertension (40.1%). After 12 months
(range: 3-29) of treatment, 29.3% of the children with
prehypertension/hypertension were normotensive. Children with systolic
prehypertension/hypertension upon entry reduced their systolic BP SDSs by 0.31
(95% confidence interval (CI): 0.70-0.83, P<0.0001). Children with diastolic
prehypertension/hypertension upon entry reduced their diastolic BP SDSs by 0.78
(95% CI: 0.78-0.86, P<0.0001). BMI SDS changes were positively associated with BP
SDS changes (P<0.0001). Nonetheless, some children reduced BP SDSs while
increasing their BMI SDSs, and prehypertension/hypertension developed in 23.3% of
the normotensive children despite reductions in BMI SDSs (P<0.0001). These
results suggest that community-based overweight and obesity treatment can reduce
BP, and thus may help improve treatment availability.
PMID- 28492241
TI - Tuning the effective spin-orbit coupling in molecular semiconductors.
AB - The control of spins and spin to charge conversion in organics requires
understanding the molecular spin-orbit coupling (SOC), and a means to tune its
strength. However, quantifying SOC strengths indirectly through spin relaxation
effects has proven difficult due to competing relaxation mechanisms. Here we
present a systematic study of the g-tensor shift in molecular semiconductors and
link it directly to the SOC strength in a series of high-mobility molecular
semiconductors with strong potential for future devices. The results demonstrate
a rich variability of the molecular g-shifts with the effective SOC, depending on
subtle aspects of molecular composition and structure. We correlate the above g
shifts to spin-lattice relaxation times over four orders of magnitude, from 200
to 0.15 MUs, for isolated molecules in solution and relate our findings for
isolated molecules in solution to the spin relaxation mechanisms that are likely
to be relevant in solid state systems.
PMID- 28492242
TI - Structure and interstitial iodide migration in hybrid perovskite methylammonium
lead iodide.
AB - Hybrid perovskites form an emerging family of exceptional light harvesting
compounds. However, the mechanism underpinning their photovoltaic effect is still
far from understood, which is impeded by a lack of clarity on their structures.
Here we show that iodide ions in the methylammonium lead iodide migrate via
interstitial sites at temperatures above 280 K. This coincides with temperature
dependent static distortions resulting in pseudocubic local symmetry. Based on
bond distance analysis, the migrating and distorted iodines are at lengths
consistent with the formation of I2 molecules, suggesting a 2I-->I2+2e- redox
couple. The actual formula of this compound is thus (CH3NH3)PbI3-2x(I2)x where
x~0.007 at room temperature. A crucial feature of the tetragonal structure is
that the methylammonium ions do not sit centrally in the A-site cavity, but
disordered around two off-centre orientations that facilitate the interstitial
ion migration via a gate opening mechanism.
PMID- 28492244
TI - Quantum physics: Atomic envoy enables molecular control.
PMID- 28492240
TI - Tau association with synaptic vesicles causes presynaptic dysfunction.
AB - Tau is implicated in more than 20 neurodegenerative diseases, including
Alzheimer's disease. Under pathological conditions, Tau dissociates from axonal
microtubules and missorts to pre- and postsynaptic terminals. Patients suffer
from early synaptic dysfunction prior to Tau aggregate formation, but the
underlying mechanism is unclear. Here we show that pathogenic Tau binds to
synaptic vesicles via its N-terminal domain and interferes with presynaptic
functions, including synaptic vesicle mobility and release rate, lowering
neurotransmission in fly and rat neurons. Pathological Tau mutants lacking the
vesicle binding domain still localize to the presynaptic compartment but do not
impair synaptic function in fly neurons. Moreover, an exogenously applied
membrane-permeable peptide that competes for Tau-vesicle binding suppresses Tau
induced synaptic toxicity in rat neurons. Our work uncovers a presynaptic role of
Tau that may be part of the early pathology in various Tauopathies and could be
exploited therapeutically.
PMID- 28492246
TI - Corrigendum: Early onset of industrial-era warming across the oceans and
continents.
PMID- 28492247
TI - Interdisciplinary debate: Agree on definitions of synchrony.
PMID- 28492243
TI - Identification of mouse cochlear progenitors that develop hair and supporting
cells in the organ of Corti.
AB - The adult mammalian cochlear sensory epithelium houses two major types of cells,
mechanosensory hair cells and underlying supporting cells, and lacks regenerative
capacity. Recent evidence indicates that a subset of supporting cells can
spontaneously regenerate hair cells after ablation only within the first week
postparturition. Here in vivo clonal analysis of mouse inner ear cells during
development demonstrates clonal relationship between hair and supporting cells in
sensory organs. We report the identification in mouse of a previously unknown
population of multipotent stem/progenitor cells that are capable of not only
contributing to the hair and supporting cells but also to other cell types,
including glia, in cochlea undergoing development, maturation and repair in
response to damage. These multipotent progenitors originate from Eya1-expressing
otic progenitors. Our findings also provide evidence for detectable regenerative
potential in the postnatal cochlea beyond 1 week of age.
PMID- 28492248
TI - PhD supervisors: invest more time.
PMID- 28492251
TI - Multi-phase volcanic resurfacing at Loki Patera on Io.
AB - The Jovian moon Io hosts the most powerful persistently active volcano in the
Solar System, Loki Patera. The interior of this volcanic, caldera-like feature is
composed of a warm, dark floor covering 21,500 square kilometres surrounding a
much cooler central 'island'. The temperature gradient seen across areas of the
patera indicates a systematic resurfacing process, which has been seen to occur
typically every one to three years since the 1980s. Analysis of past data has
indicated that the resurfacing progressed around the patera in an anti-clockwise
direction at a rate of one to two kilometres per day, and that it is caused
either by episodic eruptions that emplace voluminous lava flows or by a
cyclically overturning lava lake contained within the patera. However, spacecraft
and telescope observations have been unable to map the emission from the entire
patera floor at sufficient spatial resolution to establish the physical processes
at play. Here we report temperature and lava cooling age maps of the entire
patera floor at a spatial sampling of about two kilometres, derived from ground
based interferometric imaging of thermal emission from Loki Patera obtained on 8
March 2015 ut as the limb of Europa occulted Io. Our results indicate that Loki
Patera is resurfaced by a multi-phase process in which two waves propagate and
converge around the central island. The different velocities and start times of
the waves indicate a non-uniformity in the lava gas content and/or crust bulk
density across the patera.
PMID- 28492252
TI - Artificial intelligence: A social spin on language analysis.
PMID- 28492253
TI - Corrigendum: Adipose-derived circulating miRNAs regulate gene expression in other
tissues.
PMID- 28492254
TI - PhD supervisors: be better mentors.
PMID- 28492255
TI - Asia's glaciers are a regionally important buffer against drought.
AB - The high mountains of Asia-encompassing the Himalayas, the Hindu Kush, Karakoram,
Pamir Alai, Kunlun Shan, and Tian Shan mountains-have the highest concentration
of glaciers globally, and 800 million people depend in part on meltwater from
them. Water stress makes this region vulnerable economically and socially to
drought, but glaciers are a uniquely drought-resilient source of water. Here I
show that these glaciers provide summer meltwater to rivers and aquifers that is
sufficient for the basic needs of 136 million people, or most of the annual
municipal and industrial needs of Pakistan, Tajikistan, Turkmenistan, Uzbekistan
and Kyrgyzstan. During drought summers, meltwater dominates water inputs to the
upper Indus and Aral river basins. Uncertainties in mountain precipitation are
poorly known, but, given the magnitude of this water supply, predicted glacier
loss would add considerably to drought-related water stress. Such additional
water stress increases the risk of social instability, conflict and sudden,
uncontrolled population migrations triggered by water scarcity, which is already
associated with the large and rapidly growing populations and hydro-economies of
these basins.
PMID- 28492256
TI - Corrigendum: Photovoltage field-effect transistors.
PMID- 28492259
TI - Evolution: Sole survivor of a once-diverse lineage.
PMID- 28492258
TI - Preparation and coherent manipulation of pure quantum states of a single
molecular ion.
AB - Laser cooling and trapping of atoms and atomic ions has led to advances including
the observation of exotic phases of matter, the development of precision sensors
and state-of-the-art atomic clocks. The same level of control in molecules could
also lead to important developments such as controlled chemical reactions and
sensitive probes of fundamental theories, but the vibrational and rotational
degrees of freedom in molecules pose a challenge for controlling their quantum
mechanical states. Here we use quantum-logic spectroscopy, which maps quantum
information between two ion species, to prepare and non-destructively detect
quantum mechanical states in molecular ions. We develop a general technique for
optical pumping and preparation of the molecule into a pure initial state. This
enables us to observe high-resolution spectra in a single ion (CaH+) and coherent
phenomena such as Rabi flopping and Ramsey fringes. The protocol requires a
single, far-off-resonant laser that is not specific to the molecule, so many
other molecular ions, including polyatomic species, could be treated using the
same methods in the same apparatus by changing the molecular source. Combined
with the long interrogation times afforded by ion traps, a broad range of
molecular ions could be studied with unprecedented control and precision. Our
technique thus represents a critical step towards applications such as precision
molecular spectroscopy, stringent tests of fundamental physics, quantum computing
and precision control of molecular dynamics.
PMID- 28492260
TI - Hydrology: Asian glaciers are a reliable water source.
PMID- 28492261
TI - Science struggles on in my ravaged country.
PMID- 28492262
TI - The secret war against counterfeit science.
PMID- 28492264
TI - Censorship of addiction research is an abuse of science.
PMID- 28492263
TI - Report estimated quake death tolls to save lives.
PMID- 28492265
TI - Science publishers try new tack to combat unauthorized paper sharing.
PMID- 28492266
TI - Cell maps reveal fresh details on how the immune system fights cancer.
PMID- 28492267
TI - Ghana telescope heralds first pan-African array.
PMID- 28492268
TI - Beware the anti-science label.
PMID- 28492269
TI - NIH grant limits rile biomedical research community.
PMID- 28492270
TI - DIY gene engineering, an attack on Darwinism and a probe into Nazi science.
PMID- 28492271
TI - Satellite images reveal gaps in global population data.
PMID- 28492272
TI - Brainstorming is not the way to discuss scientific issues.
PMID- 28492274
TI - Corrigendum: Structural basis of synaptic vesicle assembly promoted by alpha
synuclein.
PMID- 28492276
TI - Dust-wind interactions can intensify aerosol pollution over eastern China.
AB - Eastern China has experienced severe and persistent winter haze episodes in
recent years due to intensification of aerosol pollution. In addition to
anthropogenic emissions, the winter aerosol pollution over eastern China is
associated with unusual meteorological conditions, including weaker wind speeds.
Here we show, based on model simulations, that during years with decreased wind
speed, large decreases in dust emissions (29%) moderate the wintertime land-sea
surface air temperature difference and further decrease winds by -0.06 (+/-0.05)
m s-1 averaged over eastern China. The dust-induced lower winds enhance
stagnation of air and account for about 13% of increasing aerosol concentrations
over eastern China. Although recent increases in anthropogenic emissions are the
main factor causing haze over eastern China, we conclude that natural emissions
also exert a significant influence on the increases in wintertime aerosol
concentrations, with important implications that need to be taken into account by
air quality studies.
PMID- 28492277
TI - Association study and expression analysis of CYP4A11 gene copy number variation
in Chinese cattle.
AB - The identification of copy number variations (CNVs) allow us to explore genomic
polymorphisms. In recent years, significant progress in understanding CNVs has
been made in studies of human and animals, however, association and expression
studies of CNVs are still in the early stage. It was previously reported that the
Cytochrome P-450 4A11 (CYP4A11) gene is located within a copy number variable
region (CNVR) that encompasses quantitative trait loci (QTLs) for economic traits
like meat quality and milk production. So, this study was performed to determine
the presence of CYP4A11 CNV in six distinct cattle breeds, identify its
relationship with growth, and explore the biological effects of gene expression.
For three CYP4A11 CNV types, Normal was more frequent than Gain or Loss.
Association analysis revealed a positive effect of CYP4A11 copy number on growth
traits (P < 0.05). One-way analysis of variance (ANOVA) analysis revealed that
more CYP4A11 copies increased the gene expression level. Moreover, overexpression
of CYP4A11 in vitro revealed its effect on lipid deposit. The data provide
evidence for the functional role of CYP4A11 CNV and provide the basis for future
applications in cattle breeding.
PMID- 28492275
TI - The transcriptional repressor complex FRS7-FRS12 regulates flowering time and
growth in Arabidopsis.
AB - Most living organisms developed systems to efficiently time environmental
changes. The plant-clock acts in coordination with external signals to generate
output responses determining seasonal growth and flowering time. Here, we show
that two Arabidopsis thaliana transcription factors, FAR1 RELATED SEQUENCE 7
(FRS7) and FRS12, act as negative regulators of these processes. These proteins
accumulate particularly in short-day conditions and interact to form a complex.
Loss-of-function of FRS7 and FRS12 results in early flowering plants with overly
elongated hypocotyls mainly in short days. We demonstrate by molecular analysis
that FRS7 and FRS12 affect these developmental processes in part by binding to
the promoters and repressing the expression of GIGANTEA and PHYTOCHROME
INTERACTING FACTOR 4 as well as several of their downstream signalling targets.
Our data reveal a molecular machinery that controls the photoperiodic regulation
of flowering and growth and offer insight into how plants adapt to seasonal
changes.
PMID- 28492278
TI - Direct and Systemic Administration of a CNS-Permeant Tamoxifen Analog Reduces
Amphetamine-Induced Dopamine Release and Reinforcing Effects.
AB - Amphetamines (AMPHs) are globally abused. With no effective treatment for AMPH
addiction to date, there is urgent need for the identification of druggable
targets that mediate the reinforcing action of this stimulant class. AMPH
stimulated dopamine efflux is modulated by protein kinase C (PKC) activation.
Inhibition of PKC reduces AMPH-stimulated dopamine efflux and locomotor activity.
The only known CNS-permeant PKC inhibitor is the selective estrogen receptor
modulator tamoxifen. In this study, we demonstrate that a tamoxifen analog, 6c,
which more potently inhibits PKC than tamoxifen but lacks affinity for the
estrogen receptor, reduces AMPH-stimulated increases in extracellular dopamine
and reinforcement-related behavior. In rat striatal synaptosomes, 6c was almost
fivefold more potent at inhibiting AMPH-stimulated dopamine efflux than
[3H]dopamine uptake through the dopamine transporter (DAT). The compound did not
compete with [3H]WIN 35,428 binding or affect surface DAT levels. Using
microdialysis, direct accumbal administration of 1 MUM 6c reduced dopamine
overflow in freely moving rats. Using LC-MS, we demonstrate that 6c is CNS
permeant. Systemic treatment of rats with 6 mg/kg 6c either simultaneously or 18
h prior to systemic AMPH administration reduced both AMPH-stimulated dopamine
overflow and AMPH-induced locomotor effects. Finally, 18 h pretreatment of rats
with 6 mg/kg 6c s.c. reduces AMPH-self administration but not food self
administration. These results demonstrate the utility of tamoxifen analogs in
reducing AMPH effects on dopamine and reinforcement-related behaviors and suggest
a new avenue of development for therapeutics to reduce AMPH abuse.
PMID- 28492280
TI - Male Dispersal Pattern in Golden Snub-nosed Monkey (Rhinopithecus roxellana) in
Qinling Mountains and its Conservation Implication.
AB - Golden snub-nosed monkey (Rhinopithecus roxellana) is one of the most endangered
primate species found in China, exhibiting multilevel society consisting of
several one-male-females together with their offspring units (OMU), and all-male
units (AMU). Female dispersal patterns of the species within herd have been well
documented, whereas those of the males within or between herds are still poorly
understood. Our results based a long-term observation indicate that more than
half of sub-adult males, and half of the deposed males that stayed a short period
in OMU disperse between herds, three of them established their own OMU in new
herd after the dispersal. Smaller number of the sub-adult and adult males,
compared with adult females, stayed in natal herd, implying sub-adult males
started dispersing and male-biased dispersal occurred between herds. High
frequencies of resident males were wounded as their OUMs were taken over, and
resident males co-operation defend bachelor males were found. Mating competition
among males within the herd may have contributed to the scenarios of male-biased
dispersal. The results also suggest that maintaining connection between isolated
herds and establishing the corridors among the fragmented habitats for the
species will greatly benefit increasing its gene flow and promoting conservation
status.
PMID- 28492279
TI - Dose-Related Effects of Adjunctive Ketamine in Taiwanese Patients with Treatment
Resistant Depression.
AB - The antidepressant effects of ketamine are thought to depend on brain-derived
neurotrophic factor (BDNF) genotype and dose. The purpose of this study was to
characterize the dose-related antidepressant effects of ketamine in patients with
treatment-resistant depression drawn from a Chinese population predominately
possessing lower activity BDNF genotypes (Val/Met, Met/Met). We conducted a
double-blind, randomized, parallel-group, placebo-controlled trial of a single
ketamine infusion (saline, 0.2 mg/kg, 0.5 mg/kg). Patients (N=71; BDNF genotype:
Val/Val (N=12, 17%), Val/Met (N=40, 56.3%), and Met/Met (N=19, 26.8%)) received
mood ratings before infusion, after infusion, and for the subsequent 14 days.
Plasma ketamine levels and BDNF genotypes were assessed. This study found a
significant dose-related ketamine effect on scores on the Hamilton Depression
Rating Scale (HAMD). The responder analysis (>50% reduction from baseline HAMD on
at least 2 days between days 2 and 5) also revealed a significant dose-related
effect (saline: 12.5%, 0.2 mg/kg: 39.1%; 0.5 mg/kg: 45.8%). This is the first
report to our knowledge to demonstrate the dose-related efficacy of R/S-ketamine
for treatment-resistant depression and the first to characterize ketamine effects
in a genotyped Chinese population in which most (83%) patients possessed at least
one copy of the lower functioning Met allele of the BDNF gene.
PMID- 28492281
TI - C. elegans chromosomes connect to centrosomes by anchoring into the spindle
network.
AB - The mitotic spindle ensures the faithful segregation of chromosomes. Here we
combine the first large-scale serial electron tomography of whole mitotic
spindles in early C. elegans embryos with live-cell imaging to reconstruct all
microtubules in 3D and identify their plus- and minus-ends. We classify them as
kinetochore (KMTs), spindle (SMTs) or astral microtubules (AMTs) according to
their positions, and quantify distinct properties of each class. While our light
microscopy and mutant studies show that microtubules are nucleated from the
centrosomes, we find only a few KMTs directly connected to the centrosomes.
Indeed, by quantitatively analysing several models of microtubule growth, we
conclude that minus-ends of KMTs have selectively detached and depolymerized from
the centrosome. In toto, our results show that the connection between centrosomes
and chromosomes is mediated by an anchoring into the entire spindle network and
that any direct connections through KMTs are few and likely very transient.
PMID- 28492283
TI - Super-diffusion of excited carriers in semiconductors.
AB - The ultrafast spatial and temporal dynamics of excited carriers are important to
understanding the response of materials to laser pulses. Here we use scanning
ultrafast electron microscopy to image the dynamics of electrons and holes in
silicon after excitation with a short laser pulse. We find that the carriers
exhibit a diffusive dynamics at times shorter than 200 ps, with a transient
diffusivity up to 1,000 times higher than the room temperature value, D0~30 cm2s
1. The diffusivity then decreases rapidly, reaching a value of D0 roughly 500 ps
after the excitation pulse. We attribute the transient super-diffusive behaviour
to the rapid expansion of the excited carrier gas, which equilibrates with the
environment in 100-150 ps. Numerical solution of the diffusion equation, as well
as ab initio calculations, support our interpretation. Our findings provide new
insight into the ultrafast spatial dynamics of excited carriers in materials.
PMID- 28492282
TI - Accumulation of heme biosynthetic intermediates contributes to the antibacterial
action of the metalloid tellurite.
AB - The metalloid tellurite is highly toxic to microorganisms. Several mechanisms of
action have been proposed, including thiol depletion and generation of hydrogen
peroxide and superoxide, but none of them can fully explain its toxicity. Here we
use a combination of directed evolution and chemical and biochemical approaches
to demonstrate that tellurite inhibits heme biosynthesis, leading to the
accumulation of intermediates of this pathway and hydroxyl radical. Unexpectedly,
the development of tellurite resistance is accompanied by increased
susceptibility to hydrogen peroxide. Furthermore, we show that the heme precursor
5-aminolevulinic acid, which is used as an antimicrobial agent in photodynamic
therapy, potentiates tellurite toxicity. Our results define a mechanism of
tellurite toxicity and warrant further research on the potential use of the
combination of tellurite and 5-aminolevulinic acid in antimicrobial therapy.
PMID- 28492286
TI - Has the SPRINT trial introduced a new blood-pressure goal in hypertension?
AB - SPRINT is the first randomized, controlled trial showing that a systolic blood
pressure goal of <120 mmHg can be attained with cardiovascular benefits in a
select group of patients with hypertension and an elevated cardiovascular risk
with different origins. Although the patient population with characteristics like
those in SPRINT makes up only 20-30% of the total hypertensive population, SPRINT
is a landmark study that highlights the need to consider lower blood- pressure
goals in the treatment of hypertension. Extending this study to include other
patient populations and geographical areas is the next step for evaluating the
benefits of strict blood-pressure targets and the generalizability of the SPRINT
results. Importantly, the blood-pressure measurement method used in SPRINT
differs from previous clinical trials, and raises the issue of whether a more
accurate method should be used in clinical trials and if such method is feasible
in clinical practice. This Perspectives article provides an analysis of the
SPRINT data, focusing on patient characteristics, blood-pressure measurement
method, and applicability of the SPRINT findings for future management
guidelines.
PMID- 28492284
TI - Inhibition of corticotropin-releasing hormone receptor 1 and activation of
receptor 2 protect against colonic injury and promote epithelium repair.
AB - Maternal separation (MS) in neonates can lead to intestinal injury. MS in
neonatal mice disrupts mucosal morphology, induces colonic inflammation and
increases trans-cellular permeability. Several studies indicate that intestinal
epithelial stem cells are capable of initiating gut repair in a variety of injury
models but have not been reported in MS. The pathophysiology of MS-induced gut
injury and subsequent repair remains unclear, but communication between the brain
and gut contribute to MS-induced colonic injury. Corticotropin-releasing hormone
(CRH) is one of the mediators involved in the brain-gut axis response to MS
induced damage. We investigated the roles of the CRH receptors, CRHR1 and CRHR2,
in MS-induced intestinal injury and subsequent repair. To distinguish their
specific roles in mucosal injury, we selectively blocked CRHR1 and CRHR2 with
pharmacological antagonists. Our results show that in response to MS, CRHR1
mediates gut injury by promoting intestinal inflammation, increasing gut
permeability, altering intestinal morphology, and modulating the intestinal
microbiota. In contrast, CRHR2 activates intestinal stem cells and is important
for gut repair. Thus, selectively blocking CRHR1 and promoting CRHR2 activity
could prevent the development of intestinal injuries and enhance repair in the
neonatal period when there is increased risk of intestinal injury such as
necrotizing enterocolitis.
PMID- 28492285
TI - Prolonged intracellular accumulation of light-inducible nanoparticles in leukemia
cells allows their remote activation.
AB - Leukaemia cells that are resistant to conventional therapies are thought to
reside in protective niches. Here, we describe light-inducible polymeric retinoic
acid (RA)-containing nanoparticles (NPs) with the capacity to accumulate in the
cytoplasm of leukaemia cells for several days and release their RA payloads
within a few minutes upon exposure to blue/UV light. Compared to NPs that are not
activated by light exposure, these NPs more efficiently reduce the clonogenicity
of bone marrow cancer cells from patients with acute myeloid leukaemia (AML) and
induce the differentiation of RA-low sensitive leukaemia cells. Importantly, we
show that leukaemia cells transfected with light-inducible NPs containing RA can
engraft into bone marrow in vivo in the proximity of other leukaemic cells,
differentiate upon exposure to blue light and release paracrine factors that
modulate nearby cells. The NPs described here offer a promising strategy for
controlling distant cell populations and remotely modulating leukaemic niches.
PMID- 28492287
TI - Dyslipidaemia: PCSK9 inhibitors and foamy monocytes in familial
hypercholesterolaemia.
PMID- 28492289
TI - Peripheral artery disease: Drug-coated balloon superior to standard balloon
angioplasty.
PMID- 28492288
TI - Epidemiology of heart failure with preserved ejection fraction.
AB - Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical
syndrome associated with poor quality of life, substantial health-care resource
utilization, and premature mortality. We summarize the current knowledge
regarding the epidemiology of HFpEF with a focus on community-based studies
relevant to quantifying the population burden of HFpEF. Current data regarding
the prevalence and incidence of HFpEF in the community as well as associated
conditions and risk factors, risk of morbidity and mortality after diagnosis, and
quality of life are presented. In the community, approximately 50% of patients
with HF have HFpEF. Although the age-specific incidence of HF is decreasing, this
trend is less dramatic for HFpEF than for HF with reduced ejection fraction
(HFrEF). The risk of HFpEF increases sharply with age, but hypertension, obesity,
and coronary artery disease are additional risk factors. After adjusting for age
and other risk factors, the risk of HFpEF is fairly similar in men and women,
whereas the risk of HFrEF is much lower in women. Multimorbidity is common in
both types of HF, but slightly more severe in HFpEF. A majority of deaths in
patients with HFpEF are cardiovascular, but the proportion of noncardiovascular
deaths is higher in HFpEF than HFrEF.
PMID- 28492290
TI - Atezolizumab: A novel PD-L1 inhibitor in cancer therapy with a focus in bladder
and non-small cell lung cancers.
AB - In recent years, immunotherapy has come to the forefront as a major development
in cancer treatment. Evasion of the immune system by tumor cells has been
identified as one of the hallmarks of cancer and multiple therapies have been
developed to counter this process. Programmed cell death 1 ligand 1 (PD-L1), a
ligand to programmed cell death protein 1 (PD-1), is expressed by many cancer
cells and the binding of PD-L1 to PD-1 results in the suppression of T-cell
mediated immune response against cancer cells. Atezolizumab is a monoclonal
antibody that binds to PD-L1 and blocks its interaction with PD-1, thereby
enhancing T-cell activity against tumor cells. Atezolizumab has been shown to be
well tolerated with no dose-limiting toxicities in phase I trials. Atezolizumab
was approved by the U.S. Food and Drug Administration in 2016 for the treatment
of platinum-resistant metastatic non-small cell lung cancer (NSCLC) and
urothelial cancer based on phase II and preliminary phase III studies that have
shown significant improvement in objective response rate and median overall
survival. There are 117 ongoing clinical trials of atezolizumab currently. Given
its efficacy in NSCLC and urothelial carcinoma, atezolizumab holds much potential
in the future of cancer therapeutics.
PMID- 28492291
TI - Crisaborole: Phosphodiesterase inhibitor for treatment of atopic dermatitis.
AB - Atopic dermatitis (AD) is an extremely common condition affecting as many as 10
20% of children and 2-10% of adults. A particularly distressing symptom of AD is
pruritus. One of the important aspects of AD is inflammation associated with
increased activity of phosphodiesterase 4 (PDE4), resulting in decreased
intracellular levels of cyclic adenosine monophosphate, which in turn causes
increased production of inflammatory cytokines. Crisaborole was developed as a
small-molecule, boron-based, selective PDE4 inhibitor that can be used topically.
Clinical trials have demonstrated its efficacy in treating patients with mild to
moderate AD, resulting in significant relief of pruritus. Unlike PDE4 inhibitors
that act systemically, crisaborole does not cause significant gastrointestinal
adverse effects. The most common adverse effect has been temporary stinging and
burning in about 4% of patients upon application of the 2% ointment. To date
there is no evidence of atrophy, telangiectasia or hypopigmentation resulting
from its use. Crisaborole is the first topically applied PDE4 inhibitor to be
approved by the FDA for use in AD.
PMID- 28492292
TI - Olaratumab for the treatment of soft tissue sarcoma.
AB - Soft tissue sarcoma represents about 1% of all solid malignancies. The standard
chemotherapy regimens have included doxorubicin alone or in combination with
other agents. Despite recent advances in treatment beyond first line - with the
FDA approval of pazopanib, eribulin and trabectidin - overall survival for
patients with metastatic disease remains in the region of 12-19 months.
Olaratumab is a monoclonal antibody directed against platelet-derived growth
factor receptor alpha (PDGFRalpha). It was studied in a phase Ib and randomized
phase II study in combination with doxorubicin in patients with soft tissue
sarcoma who previously had not received doxorubicin for metastatic disease. The
results of the phase II study showed a statistically significant improvement in
progression-free survival up to 6 months, and a more dramatic improvement in
overall survival to 26.9 months. This is the first randomized trial to show a
significant improvement in overall survival compared to doxorubicin alone. An
ongoing phase III study has completed accrual and results are being analyzed.
Olaratumab has been granted accelerated approval by the United States Food and
Drug Administration. Ongoing trials are underway to further demonstrate the
mechanism of action. This review will document the studies involved in the
development of olaratumab in the treatment of soft tissue sarcomas.
PMID- 28492293
TI - European Association of Urology - 32nd Annual Congress (March 24-28, 2017 -
London, UK).
AB - The European Association of Urology (EAU) Congress is Europe's biggest urological
event and this year's meeting, in London, UK, brought together more than 13,000
participants from over 100 countries to discuss the latest research in this
field. With 5 days' worth of lectures, debates, learning courses, presentations
and live surgeries the congress provided plenty of opportunity to learn from the
1,400 experts presenting, as well as to network with international peers.
PMID- 28492294
TI - Effect of remifentanil for general anesthesia on parturients and newborns
undergoing cesarean section: a meta-analysis.
AB - INTRODUCTION: The results presented by studies investigating the effect of
remifentanil on both parturients and newborns during cesarean section differed
significantly. Therefore, we performed a meta-analysis to estimate the effect of
remifentanil on these patients. EVIDENCE ACQUISITION: Potentially eligible
studies published before 15 March 2016 were searched through four databases
including PubMed, SCOPUS, ISI web of knowledge and EBSCO. Weighted mean
difference (WMD) or odds ratios (ORs) and the corresponding 95% confidence
interval (CI) were applied to estimate the strength of relationship. EVIDENCE
SYNTHESIS: A total number of seven randomized-controlled trials were included in
this meta-analysis. The results showed that Apgar values at 1 min and 5 min were
significantly lower in the infants of remifentanil-treated mothers, with the WMD
and corresponding 95% CI of -0.835 (-1.515, -0.154) and -0.296 (-0.570, -0.021),
respectively. The pH value of umbilical artery was significantly higher in the
remifentanil group (WMD: 0.014, 95% CI: 0.002, 0.025). The highest and lowest
systolic blood pressures were significantly lower in remifentanil-treated
mothers, with the WMD and corresponding 95% CI of -18.913 (-34.468, -3.359) and
12.982 (-21.479, -4.485), respectively. CONCLUSIONS: Remifentanil shows potential
value of maternal circulation response during general anesthesia, which reduces
maternal blood pressure in response to intubation and surgery. However, whether
it is beneficial for the neonate is still controversial. More randomized
controlled trials with larger sample size are required to assess the adverse
effects of remifentanil.
PMID- 28492295
TI - Elderly versus non-elderly patients with intra-abdominal candidiasis in the ICU.
AB - BACKGROUND: Intra-abdominal candidiasis (IAC) has a considerable cost in terms of
mortality and morbidity. We sought to study the epidemiology, characteristics and
outcome of elderly (>75 years old) versus non-elderly patients with IAC and risk
factors for mortality in elderly patients. METHODS: Post-hoc analysis of a
retrospective multinational cohort study over a 3-year period (2011-2013).
RESULTS: Of 482 patients, 124 (25.7%) were elderly and 358 (74.3%) were non
elderly. The mean age was 80.4+/-3.9 and 56.3+/-13.8 years, respectively. Fifty
four of 124 (43.5%) and 75/358 (20.9%) died until the end of observation. The
majority of isolates were Candida albicans. Echinocandins were the most
prescribed initial agent. Elderly patients were more likely to have a higher
APACHE II Score, and to suffer from chronic obstructive pulmonary disease and
heart disease. Non-elderly patients were more likely to be treated with
immunosuppressants and steroids, and to have received solid organ
transplantation. Mortality was significantly higher in the elderly group.
Regarding risk factors for mortality in elderly patients, non-survivors were more
likely to be males, reoperated, develop septic shock, receive vasopressors,
suffer from end-stage renal disease (ESRD), and have inadequate abdominal source
control within 48 hours. They had a higher APACHE II Score and a higher number of
acquired organ dysfunction. ESRD and inadequate abdominal source control were
significantly associated with mortality. CONCLUSIONS: Factors independently
predicting mortality in elderly patients with IAC were ESRD and inadequate
abdominal source control. Elderlies were found to have more pulmonary and cardiac
morbidities and had higher mortality than non-elderlies.
PMID- 28492296
TI - Italian COnsensus in Neuroradiological Anesthesia (ICONA).
AB - Anesthetic management of patients undergoing endovascular procedures for treating
intracranial aneurysms or cerebrovascular malformations must consider a number of
specific challenges, in addition to those associated with anesthesia for other
specialties. In addition to maintenance of physiological stability, manipulation
of systemic and cerebral hemodynamic parameters may be required to treat any
sudden unexpected catastrophic neurological events. A multidisciplinary group
including neuro- and pediatric anesthesiologists, interventional
neuroradiologists, neurosurgeons, and a clinical methodologist contributed to
this document. This consensus working group from 21 Italian institutions
identified open questions regarding the best practices for management of
anesthesia during endovascular neuroradiological procedures for intracranial
aneurysms and cerebrovascular malformations, and addressed these by formulating
practical consensus statements. At the first meeting in November 2015, nine key
areas were identified regarding choice of anesthetic, patient monitoring,
hemodynamic targets, postoperative care, and the management of neuromuscular
blockade, anticoagulant and/or antiplatelet therapy, and special considerations
for pediatric patients. Nine subgroups were established and a medical librarian
performed literature searches in the Cochrane and MEDLINE/PubMed databases for
each group. Groups drafted literature summaries and provisional responses in the
form of candidate consensus statements based on evidence, when possible, and
clinical experience, when this was lacking. Final wording was agreed at a meeting
in April 2016 and where possible evidence was graded using United States
Preventive Services Task Force criteria. Consensus (defined as >90% agreement)
was based on evidence, clinical experience, clinician preference, feasibility in
the Italian healthcare system, and cost/benefit considerations.
PMID- 28492297
TI - Recent antiseizure medications in the Intensive Care Unit.
AB - BACKGROUND: Seizures and status epilepticus (SE), both clinical and subclinical,
are frequent in critically ill patients. The list of available antiseizure
medications (ASMs) is expanding and now includes older and widely used drugs as
well as more recent medications with a better safety and pharmacokinetics
profile. METHODS: We review a selection of recent publications about the
indications and administration of ASMs in critical care for the prophylaxis and
treatment of seizures and SE, focusing on recent ASMs available as intravenous
formulation and emphasizing pharmacokinetics and safety issues in relation to
several aspects of critical illness. RESULTS: Levetiracetam, lacosamide and more
recently brivaracetam, represent interesting alternatives to older ASMs, mostly
due to a more favorable safety and pharmacokinetic profile. Low-quality studies
suggest that this profile results in better tolerability in treated patients.
Ketamine might represent a useful addition in our anesthetic armamentarium for
refractory SE, due to its different mechanism of action and cardiovascular
properties. Little evidence is available however to support the prophylactic use
of ASMs in critically ill patients, except in specific settings (traumatic brain
injury and subarachnoid hemorrhage). Head-to-head studies comparing recent and
older ASMs in the treatment of acute seizures and SE are ongoing or awaiting
publication. Administration of ASMs to critically ill patients needs to be
adapted to organ dysfunction, and especially to renal dysfunction for recent
drugs. CONCLUSIONS: Recent ASMs and could represent better treatment choices in
critically ill patients than older ones but this needs to be confirmed in
randomized controlled studies. In general, further studies are required to
clarify the indications and optimal use of ASMs in the critical care setting.
PMID- 28492298
TI - Use of the ultrasound-guided erector spinae plane block in breast surgery.
PMID- 28492299
TI - Extraglottic airway devices and ultrasound airway evaluation: are we on the right
track?
PMID- 28492300
TI - Rational Design and Construction of Well-Organized Macro-Mesoporous SiO2/TiO2
Nanostructure toward Robust High-Performance Self-Cleaning Antireflective Thin
Films.
AB - Antireflection (AR) thin films on optical substrates are of great significance in
high-performance optoelectronic devices. Here, we present a rational design and
construction of well-organized macro-mesoporous nanostructure toward robust high
performance self-cleaning antireflective thin films on the basis of effective
medium theory and finite difference time domain (FDTD) simulations that combine
the optical design principle. A hierarchical macro-mesoporous SiO2 thin film with
very high porosity and gradient refractive indexes works as a lambda/4-wavelength
AR layer and significantly suppresses the reflection in the range from 350 to
1200 nm. Even after dip-coating a layer of high refractive index TiO2
nanocrystals, the nanostructured thin film still exhibits broadband AR properties
which are much superior to conventional flat SiO2/TiO2 thin films, especially in
the range of 350-500 nm. In addition, the obtained thin film exhibits
photocatalytic self-cleaning and durable superhydrophilicity. The advantages
brought by the well-organized macro-mesoporous structure are also testified
through comparing to the solely mesoporous SiO2/TiO2 film counterpart. Moreover,
the pencil hardness test and sandpaper abrasion test show favorable robustness
and functional durability of the thin film, which make it extremely attractive
for practical applications in optical devices, display devices, and photovoltaic
cells.
PMID- 28492301
TI - High-Affinity RGD-Knottin Peptide as a New Tool for Rapid Evaluation of the
Binding Strength of Unlabeled RGD-Peptides to alphavbeta3, alphavbeta5, and
alpha5beta1 Integrin Receptors.
AB - We describe a highly sensitive competition ELISA to measure integrin-binding of
RGD-peptides in high-throughput without using cells, ECM-proteins, or antibodies.
The assay measures (nonlabeled) RGD-peptides' ability to inhibit binding of a
biotinylated "knottin"-RGD peptide to surface-immobilized integrins and, thus,
enables quantification of the binding strength of high-, medium-, and low
affinity RGD-binders. We introduced the biotinylated knottin-RGD peptide instead
of biotinylated cyclo[RGDfK] (as reported by Piras et al.), as integrin-binding
was much stronger and clearly detectable for all three integrins. In order to
maximize sensitivity and cost-efficiency, we first optimized several parameters,
such as integrin-immobilization levels, knottin-RGD concentration, buffer
compositions, type of detection tag (biotin, His- or cMyc-tag), and spacer
length. We thereby identified two key factors, that is, (i) the critical spacer
length (longer than Gly) and (ii) the presence of Ca2+ and Mg2+ in all incubation
and washing buffers. Binding of knottin-RGD peptide was strongest for alphavbeta3
but also detectable for both alphavbeta5 and alpha5beta1, while binding of
biotinylated cyclo[RGDfK] was very weak and only detectable for alphavbeta3. For
assay validation, we finally determined IC50 values for three unlabeled peptides,
that is: (i) linear GRGDS, (ii) cyclo[RGDfK], and (iii) the knottin-RGD itself
for binding to three different integrin receptors (alphavbeta3, alphavbeta5,
alpha5beta1). Major benefits of the novel assay are (i) the extremely low
consumption of integrin (50 ng/peptide), (ii) the fact that neither
antibodies/ECM-proteins nor integrin-expressing cells are required for detection,
and (iii) its suitability for high-throughput screening of (RGD-)peptide
libraries.
PMID- 28492302
TI - Metal-Organic Framework Templated Catalysts: Dual Sensitization of PdO-ZnO
Composite on Hollow SnO2 Nanotubes for Selective Acetone Sensors.
AB - Metal-organic framework (MOF)-derived synergistic catalysts were easily
functionalized on hollow SnO2 nanotubes (NTs) via electrospinning and subsequent
calcination. Nanoscale Pd NPs (~2 nm) loaded Zn-based zeolite imidazole framework
(Pd@ZIF-8, ~80 nm) was used as a new catalyst-loading platform for the effective
functionalization of a PdO@ZnO complex catalyst onto the thin wall of one
dimensional metal oxide NTs. The well-dispersed nanoscale PdO catalysts (3-4 nm)
and multiheterojunctions (PdO/ZnO and ZnO/SnO2) on hollow structures are
essential for the development of high-performance gas sensors. As a result, the
PdO@ZnO dual catalysts-loaded hollow SnO2 NTs (PdO@ZnO-SnO2 NTs) exhibited high
acetone response (Rair/Rgas = 5.06 at 400 degrees C @ 1 ppm), superior acetone
selectivity against other interfering gases, and fast response (20 s) and
recovery (64 s) time under highly humid atmosphere (95% RH). In this work, the
advantages of hollow SnO2 NT structures with high surface area and open porosity
were clearly demonstrated by the comparison to SnO2 nanofibers (NFs). Moreover,
the sensor arrays composed of SnO2 NFs, SnO2 NTs, PdO@ZnO-SnO2 NFs, and PdO@ZnO
SnO2 NTs successfully identified the patterns of the exhaled breath of normal
people and simulated diabetics by using a principal component analysis.
PMID- 28492303
TI - A Unique "Integration" Strategy for the Rational Design of Optically Tunable Near
Infrared Fluorophores.
AB - Fluorescence imaging is a rapidly growing technique for noninvasive imaging of
biological molecules and processes with high spatial and temporal resolution. For
effective biological imaging, it is essential and important to develop robust
fluorescent dyes, in particular, near-infrared (NIR) fluorescent dyes with
favorable optical properties. Compared with the visible light emitting dyes, NIR
dyes have relatively longer emission wavelengths (650-900 nm) with lower energy
and are advantageous as imaging agents owing to the minimum photodamage of NIR
light to biological samples, deep penetration into tissues, and low interference
from autofluorescence of biomolecules. Although great efforts have been devoted
to engineer NIR fluorophores, it is still very challenging to regulate their
photophysical properties as they often lack optically tunable mechanisms, and
this shortcoming considerably restricts the realization of their full potential.
Consequently, the rational design of small-molecule optically tunable NIR
fluorophores is of high priority and great value. In general, two key
characteristics are indispensable for designing excellent optically tunable NIR
fluorescent dyes. First, NIR fluorescent dyes should display the maximal
absorption and emission located in the NIR region and also have the prominent
properties including excellent fluorescence quantum yields, large Stokes shifts,
good chemical stability and photostability, low cytotoxicity, and desirable
compatibility with biological systems. Second, in principle, functional NIR dyes
should also possess optically tunable groups, which can be easily modified to
afford responsive sites for the targets of interest. With these considerations in
mind, in this Account, we described a unique "integration" strategy for judicious
design of the optically tunable NIR fluorophores, which are an intuitive
combination of the traditional NIR dyes and the optically tunable mechanisms in
the visible light emissive dyes. Thus, the versatile strategy may allow not only
retention of the NIR emission properties of NIR dyes but also inheritance of the
optically tunable mechanisms from the visible light emissive dyes. By the unique
integration strategy, a built-in optically tunable group is strategically
installed into the traditional NIR fluorescent dyes to directly tune their
optical properties. Herein, we present a concise review of the rational design
strategy and biological applications of small-molecule optically tunable NIR
fluorescent dyes via the unique integration strategy, and we focused mainly on
our work and some representative examples from other groups based on our NIR
platforms. This Account includes the detailed integration strategy of each class
of the NIR fluorescent dyes, the development of their derivatives, and their
imaging applications in living systems.
PMID- 28492304
TI - Deep-Red Fluorescent Gold Nanoclusters for Nucleoli Staining: Real-Time
Monitoring of the Nucleolar Dynamics in Reverse Transformation of Malignant
Cells.
AB - Nucleoli are important subnuclear structures inside cells. We report novel
fluorescent gold nanoclusters (K-AuNCs) that are able to stain the nucleoli
selectively and make it possible to explore the nucleolar morphology with
fluorescence imaging technique. This novel probe is prepared through an easy
synthesis method by employing a tripeptide (Lys-Cys-Lys) as the surface ligand.
The properties, including deep-red fluorescence emission (680 nm), large Stocks
shift, broad excitation band, low cytotoxicity, and good photostability, endow
this probe with potential for bioanalytical applications. Because of their small
size and their positively charged surface, K-AuNCs are able to accumulate
efficiently at the nucleolar regions and provide precise morphological
information. K-AuNCs are also used to monitor the nucleolar dynamics along the
reverse-transformation process of malignant cells, induced by the agonist of
protein A, 8-chloro-cyclic adenosine monophosphate. This gives a novel approach
for investigating the working mechanism of antitumor drugs.
PMID- 28492305
TI - Monitoring Interfacial Lipid Oxidation in Oil-in-Water Emulsions Using Spatially
Resolved Optical Techniques.
AB - The oxidation of lipids is an important phenomenon with ramifications for
disciplines that range from food science to cell biology. The development and
characterization of tools and techniques to monitor lipid oxidation are thus
relevant. Of particular significance in this regard are tools that facilitate the
study of oxidations at interfaces in heterogeneous samples (e.g., oil-in-water
emulsions, cell membranes). In this article, we establish a proof-of-principle
for methods to initiate and then monitor such oxidations with high spatial
resolution. The experiments were performed using oil-in-water emulsions of
polyunsaturated fatty acids (PUFAs) prepared from cod liver oil. We produced
singlet oxygen at a point near the oil-water interface of a given PUFA droplet in
a spatially localized two-photon photosensitized process. We then followed the
oxidation reactions initiated by this process with the fluorescence-based imaging
technique of structured illumination microscopy (SIM). We conclude that the
approach reported herein has attributes well-suited to the study of lipid
oxidation in heterogeneous samples.
PMID- 28492306
TI - Large Lateral Photovoltage Observed in MoS2 Thickness-Modulated ITO/MoS2/p-Si
Heterojunctions.
AB - Molybdenum disulfide (MoS2), as a typical two-dimensional (2D) material, has
attracted extensive attention in recent years because of its fascinating optical
and electric properties. However, the applications of MoS2 have been mainly in
photovoltaic devices, field-effect transistors, photodetectors, and gas sensors.
Here, it is demonstrated that MoS2 can be found another important application in
position sensitive detector (PSD) based on lateral photovoltaic effect (LPE) in
it. The ITO/MoS2(3, 5, 7, 9, 10, 20, 50, 100 nm)/p-Si heterojunctions were
successfully prepared with vertically standing nanosheet structure of MoS2.
Because of the special structure and the strong light absorption of the
relatively thick MoS2 film, the ITO/MoS2/p-Si heterojunction exhibits an abnormal
thickness-dependent LPE, which can be ascribed to the n- to p-type transformation
of MoS2. Moreover, the LPE of ITO/MoS2/p-Si structure improves greatly because of
forward enhanced built-in field by type transformation in a wide spectrum
response ranging from visible to near-infrared, especially the noticeable
improvement in infrared region, indicating its great potential application in
infrared PSDs. This work not only suggest that the ITO/MoS2/p-Si heterojunction
shows great potential in LPE-based sensors, but also unveils the importance of
type transformation of MoS2 in MoS2-based photoelectric devices besides strong
light absorption and suitable bandgap.
PMID- 28492307
TI - Sensitive Quantification of MicroRNAs by Isothermal Helicase-Dependent
Amplification.
AB - Dysregulation of microRNA expression levels is closely associated with a variety
of human diseases, and their rapid and sensitive quantification is essential to
clinical diagnosis and therapy. Because of their poor sensitivity, conventional
quantification methods are unable to detect low-abundance microRNAs.
Alternatively, nucleic acid amplification approaches have been introduced to
improve the detection sensitivity, but most of them involve complicated probe
design and time-consuming procedures. Herein, we report a simple, rapid, and
sensitive fluorescent method for label-free detection of low-abundance microRNAs
based on isothermal helicase-dependent amplification. In this assay, the target
microRNA may specifically hybridize with the 3'-terminus of the linear probe to
form a DNA-microRNA heteroduplex, protecting the probes from exonuclease I
digestion. The remaining probes may be subsequently amplified by helicase
dependent amplification, generating an ultrahigh fluorescence signal within 30
min. This assay is very sensitive with a low detection limit of 12.8 fM and
exhibits a large dynamical range from 100 fM to 10 nM. Moreover, this assay can
discriminate different microRNA family members, and it can be used to absolutely
quantify endogenous microRNA of total RNA samples extracted from cancer cells,
providing a powerful tool for biomedical research and clinical diagnostics.
PMID- 28492308
TI - Visualizing the Conversion Process of Alcohol-Induced Fatty Liver to
Steatohepatitis in Vivo with a Fluorescent Nanoprobe.
AB - Excess alcohol consumption and the associated development of alcoholic liver
disease (ALD) are major public health challenges worldwide. Since patients with
the severe stages of ALD no longer benefit from clinical therapies, early warning
of ALD holds significant promise for increasing the cure rate of ALD. Herein, we
develop a bicolor fluorescent nanoprobe for dynamically monitoring the conversion
process of alcohol-induced fatty liver to steatohepatitis in vivo through
simultaneous imaging of microRNA 155 and osteopontin mRNA, which are related to
fatty liver and steatohepatitis, respectively. The fluorescence imaging results
indicate that the nanoprobe can effectively differentiate alcohol-induced fatty
liver and steatohepatitis. Moreover, the nanoprobe can monitor the transmutation
process of alcohol-induced fatty liver to steatohepatitis and assess the
remission effects of N-acetyl cysteine for alcohol-induced liver injury. We
anticipate the developed nanoprobe and imaging method can provide new ways for
early warning, treatments, and prognosis of ALD.
PMID- 28492309
TI - Competitive Inhibition Mechanism of Acetylcholinesterase without Catalytic Active
Site Interaction: Study on Functionalized C60 Nanoparticles via in Vitro and in
Silico Assays.
AB - Acetylcholinesterase (AChE) activity regulation by chemical agents or,
potentially, nanomaterials is important for both toxicology and pharmacology.
Competitive inhibition via direct catalytic active sites (CAS) binding or
noncompetitive inhibition through interference with substrate and product
entering and exiting has been recognized previously as an AChE-inhibition
mechanism for bespoke nanomaterials. The competitive inhibition by peripheral
anionic site (PAS) interaction without CAS binding remains unexplored. Here, we
proposed and verified the occurrence of a presumed competitive inhibition of AChE
without CAS binding for hydrophobically functionalized C60 nanoparticles (NPs) by
employing both experimental and computational methods. The kinetic inhibition
analysis distinguished six competitive inhibitors, probably targeting the PAS,
from the pristine and hydrophilically modified C60 NPs. A simple quantitative
nanostructure-activity relationship (QNAR) model relating the pocket accessible
length of substituent to inhibition capacity was then established to reveal how
the geometry of the surface group decides the NP difference in AChE inhibition.
Molecular docking identified the PAS as the potential binding site interacting
with the NPs via a T-shaped plug-in mode. Specifically, the fullerene core
covered the enzyme gorge as a lid through pi-pi stacking with Tyr72 and Trp286 in
the PAS, while the hydrophobic ligands on the fullerene surface inserted into the
AChE active site to provide further stability for the complexes. The modeling
predicted that inhibition would be severely compromised by Tyr72 and Trp286
deletions, and the subsequent site-directed mutagenesis experiments proved this
prediction. Our results demonstrate AChE competitive inhibition of NPs without
CAS participation to gain further understanding of both the neurotoxicity and the
curative effect of NPs.
PMID- 28492310
TI - Raster-Mode Continuous-Flow Liquid Microjunction Mass Spectrometry Imaging of
Proteins in Thin Tissue Sections.
AB - Mass spectrometry imaging by use of continuous-flow liquid microjunction sampling
at discrete locations (array mode) has previously been demonstrated. In this
Letter, we demonstrate continuous-flow liquid microjunction mass spectrometry
imaging of proteins from thin tissue sections in raster mode and discuss
advantages (a 10-fold reduction in analysis time) and challenges (suitable
solvent systems, data interpretation) of the approach. Visualization of data is
nontrivial, requiring correlation of solvent-flow, mass spectral data acquisition
rate, data quality, and liquid microjunction sampling area. The latter is
particularly important for determining optimum pixel size. The minimum achievable
pixel size is related to the scan time of the instrument used. Here we show a
minimum achievable pixel size of 50 MUm (x-dimension) when using an Orbitrap
Elite; however a pixel size of 600 MUm is recommended in order to minimize the
effects of oversampling on image accuracy.
PMID- 28492311
TI - Pressure-Sensitive and Conductive Carbon Aerogels from Poplars Catkins for
Selective Oil Absorption and Oil/Water Separation.
AB - Multifunctional carbon aerogels that are both highly compressible and conductive
have broad potential applications in the range of sound insulator, sensor, oil
absorption, and electronics. However, the preparation of such carbon aerogels has
been proven to be very challenging. Here, we report fabrication of pressure
sensitive and conductive (PSC) carbon aerogels by pyrolysis of cellulose aerogels
composed of poplars catkin (PC) microfibers with a tubular structure. The wet PC
gels can be dried directly in an oven without any deformation, in marked contrast
to the brittle nature of traditional carbon aerogels. The resultant PSC aerogels
exhibit ultralow density (4.3 mg cm-3), high compressibility (80%), high
electrical conductivity (0.47 S cm-1), and high absorbency (80-161 g g-1) for
oils and organic liquids. The PSC aerogels have potential applications in various
fields such as elastomeric conductors, absorption of oils from water and
oil/water separation, as the PSC aerogels feature simple preparation process with
low-cost biomass as the precursor.
PMID- 28492312
TI - Synthesis and Characterization of Graphene Oxide-Polystyrene Composite Capsules
with Aqueous Cargo via a Water-Oil-Water Multiple Emulsion Templating Route.
AB - Graphene oxide/polystyrene (GO/PS) nanocomposite capsules containing a two
compartment cargo have been successfully fabricated using a Pickering emulsion
strategy. Highly purified GO sheets with typically micrometer-scale lateral
dimensions and amphiphilic characteristics were prepared from the oxidation
reaction of graphite with concomitant exfoliation of the graphite structure.
These GO sheets were employed as a stabilizer for oil-in-water emulsions where
the oil phase comprised toluene or olive oil. The stability and morphology of the
emulsions were extensively studied as a function of different parameters
including GO concentration, aqueous phase pH, ultrasonication time, effects of
added electrolytes and stability to dilution. In selected conditions, the olive
oil emulsions showed spontaneous formation of multiple w/o/w emulsions with high
stability, whereas toluene formed simple o/w emulsions of lower overall
stability. Olive oil emulsions were therefore used to prepare capsules templated
from emulsion droplets by surrounding the oil phase with a GO/PS shell. The GO
sheets, emulsions and composite capsules were characterized using a variety of
physical and spectroscopic techniques in order to unravel the interactions
responsible for capsule formation. The ability of the capsules to control the
release of a model active agent in the form of a hydrophilic dye was explored,
and release kinetics were monitored using UV-visible spectroscopy to obtain rate
parameters. The composite capsules showed promising sustained release properties,
with release rates 11* lower than the precursor GO-stabilized multiple emulsion
droplets.
PMID- 28492314
TI - The Synthesis of Chiral beta,beta-Diaryl Allylic Alcohols and Their Use in the
Preparation of alpha-Tertiary Allylamines and Quaternary alpha-Amino Acids.
AB - An approach to nonracemic beta,beta-diarylsubstituted allyl alcohols is
described. Their synthesis starts from l-lactic acid-derived propargyl alcohol,
which is submitted to sequential Sonogashira/Suzuki or Sonagashira/Stille
coupling reactions. Both approaches enable the synthesis of either (Z)- or (E)
allylic alcohols regarding the order of introducing coupling agents. The obtained
allyl alcohols were applied in the synthesis of nonracemic alpha-tertiary
allylamines via stereocontrolled cyanate-to-isocyanate sigmatropic rearrangement
reactions of the corresponding allyl carbamates. The stereoselectivity of the
process is controlled by the geometry of the double bond of the starting allyl
derivative. As demonstrated, a rearrangement of (S,Z)-allyl carbamates provides
(S)-teriary allylamines, whereas the transformation (S,E)-isomers leads to (R)
allylamines.
PMID- 28492313
TI - Size, Composition, and Source Profiles of Inhalable Bioaerosols from Colorado
Dairies.
AB - Particulate matter emissions from agricultural livestock operations contain both
chemical and biological constituents that represent a potential human health
hazard. The size and composition of these dusts, however, have not been well
described. We evaluated the full size distribution (from 0 to 100 MUm in
aerodynamic diameter) and chemical/biological composition of inhalable dusts
inside several Colorado dairy parlors. Four aerodynamic size fractions (<3, 3-10,
10-30, and >30 MUm) were collected and analyzed using a combination of
physiochemical techniques to understand the structure of bacterial communities
and chemical constituents. Airborne particulate mass followed a bimodal size
distribution (one mode at 3 MUm and a second above 30 MUm), which also correlated
with the relative concentrations of the following microbiological markers:
bacterial endotoxin, 3-hydroxy fatty acids, and muramic acid. Sequencing of the
16S-rRNA components of this aerosol revealed a microbiome derived predominantly
from animal sources. Bacterial genera included Staphlyococcus, Pseudomonas, and
Streptococcus, all of which have proinflammatory and pathogenic capacity. Our
results suggest that the size distribution of bioaerosols emitted by dairy
operations extends well above 10 MUm in diameter and contains a diverse mixture
of potentially hazardous constituents and opportunistic pathogens. These findings
should inform the development of more effective emissions control strategies.
PMID- 28492315
TI - Missing Food, Missing Data? A Critical Review of Global Food Losses and Food
Waste Data.
AB - Food losses and food waste (FLW) have become a global concern in recent years and
emerge as a priority in the global and national political agenda (e.g., with
Target 12.3 in the new United Nations Sustainable Development Goals). A good
understanding of the availability and quality of global FLW data is a
prerequisite for tracking progress on reduction targets, analyzing environmental
impacts, and exploring mitigation strategies for FLW. There has been a growing
body of literature on FLW quantification in the past years; however, significant
challenges remain, such as data inconsistency and a narrow temporal,
geographical, and food supply chain coverage. In this paper, we examined 202
publications which reported FLW data for 84 countries and 52 individual years
from 1933 to 2014. We found that most existing publications are conducted for a
few industrialized countries (e.g., the United Kingdom and the United States),
and over half of them are based only on secondary data, which signals high
uncertainties in the existing global FLW database. Despite these uncertainties,
existing data indicate that per-capita food waste in the household increases with
an increase of per-capita GDP. We believe that more consistent, in-depth, and
primary-data-based studies, especially for emerging economies, are badly needed
to better inform relevant policy on FLW reduction and environmental impacts
mitigation.
PMID- 28492316
TI - Environmentally Persistent Free Radicals in Soils of Past Coking Sites:
Distribution and Stabilization.
AB - This study presents the existence of environmentally persistent free radicals
(EPFRs) in soils of past coking sites, mainly contaminated by polycyclic aromatic
hydrocarbons (PAHs). Measurements of EPFRs were conducted by electron
paramagnetic resonance (EPR) technique with numerous soil samples, which were
collected from different distances (0-1000 m) and different depths (0-30 cm) of
three contaminant sources. EPR signals with ~3 * 1017 radicals/g of the soil
samples were obtained, which are very similar to that generated in PAHs
contaminated clays, that is, g = 2.0028-2.0036. Concentrations of PAHs and soil
components were determined to understand their role in producing EPFRs. PAHs,
clay, and iron predominately contributed to generating EPRFs. Meanwhile, organic
matter negatively influenced the production of EPRFs. The effects of
environmental factors (moisture and oxic/anoxic) were also studied to probe the
persistency of EPFRs under various simulated conditions. The EPFRs are stable
under relatively dry and oxic conditions. Under anoxic conditions without O2 and
H2O, the spin densities decrease initially, followed by gradual increase before
attaining constant values in two months period time. The present work implies
that continuous formation of EPFRs induced by PAHs is largely responsible for the
presence of relatively stable radicals in soils of coking sites.
PMID- 28492317
TI - Discovery of a Potent Nonpeptidomimetic, Small-Molecule Antagonist of Cellular
Inhibitor of Apoptosis Protein 1 (cIAP1) and X-Linked Inhibitor of Apoptosis
Protein (XIAP).
AB - XIAP and cIAP1 are members of the inhibitor of apoptosis protein (IAP) family and
are key regulators of anti-apoptotic and pro-survival signaling pathways.
Overexpression of IAPs occurs in various cancers and has been associated with
tumor progression and resistance to treatment. Structure-based drug design (SBDD)
guided by structural information from X-ray crystallography, computational
studies, and NMR solution conformational analysis was successfully applied to a
fragment-derived lead resulting in AT-IAP, a potent, orally bioavailable, dual
antagonist of XIAP and cIAP1 and a structurally novel chemical probe for IAP
biology.
PMID- 28492319
TI - Zero in-Plane Thermal Expansion in Guest-Tunable 2D Coordination Polymers.
AB - Zero in-plane thermal expansion (TE) in a two-dimensional (2D) coordination
polymer is demonstrated. The combination of components that expand and those that
shrink into zigzag layers results in no net area change in the 2D materials with
temperature. Single crystals of [Mn(salen)]2[Mn(N)(CN)4(guest)] (salen = N,N'
ethylenebis(salicylideneaminato), guest = MeOH and MeCN) were prepared, and
variable-temperature single-crystal X-ray structural analyses demonstrated that
these compounds exhibited both anisotropic positive and negative thermal
expansion depending on the guest species. The TE behavior results from
distortions of the octahedral coordination geometry of [Mn(salen)]+ units in the
zigzag layers. When both guests MeOH and MeCN were incorporated into one
material, [Mn(salen)]2[Mn(N)(CN)4(MeOH)0.25(MeCN)0.75], zero in-plane TE resulted
in a range of temperature between 380 and 440 K.
PMID- 28492318
TI - Effect of Deuteration on the Thermodynamic Properties of
Dioxotetrafluoromolybdate(VI), (NH4)2MoO2F4.
AB - Thermal and dielectric studies of (ND4)2MoO2F4 crystals undergoing successive
phase transitions at T1 = 272 K and T2 = 181 K showed that deuteration is
accompanied by an increase in the chemical pressure in the crystal lattice
(Deltap ~ 0.02 GPa), which shifts the Cmcm <-> Pnma transformation for the first
order to the tricritical point. The direct participation of ammonium groups in
the mechanism of structural distortions is demonstrated by a decrease in the
entropy of the high-temperature phase transition (DeltaS1 = R ln 6.0). An
external hydrostatic pressure leads to an expansion of the temperature interval
of the intermediate antiferroelectric Pnma phase. The triple point on the T-p
phase diagram, where the Cmcm, Pnma, amd Pnma* phases coexist, can be realized at
a negative pressure of ptrp ~ -0.8 GPa.
PMID- 28492320
TI - Hydrazine-Assisted Syntheses and Properties of Mercury Tellurides Containing
Transition-Metal Complexes.
AB - With assistance of reactive and coordinative hydrazine, transition-metal
telluromercurates [Mn(trien)(N2H4)2]2[Hg2Te4]2 (A), [Zn(trien)(N2H4)2]Hg2Te4 (B),
[Mn(tepa)(N2H4)]2Hg4Te12 (C), [TM(trien)(Hg2Te4)] (TM = Mn (D), Zn (E)), and
[Zn(atep)]2Hg5Te12 (atep = 4-(2-aminoethyl)triethylenetetramine) (F) were
solvothermally prepared in triethylenetetramine (trien) or tetraethylenepentamine
(tepa) solvents using elemental Te as precursor in lower temperature range.
Compounds A and B consist of mixed coordination cations [TM(trien)(N2H4)2]2+ (TM
= Mn, Zn) and one-dimensional polyanion [Hg2Te4]2- with the five-membered Hg2Te3
rings being coplanar. Compound C is composed of two [Mn(tepa)(N2H4)]2+ cations
and a [Hg4Te12]4- cluster with a centrosymmetric structure. Compounds D and E
consist of coordination polymer [TM(trien) (Hg2Te4)] containing novel doubled
[Hg2Te4]n chain with tetrahedrally coordinated Hg(II) centers, which is quite
different from the common single chain with the same composition of [Hg2Te4]n. D
and E are the first examples of telluromercurates incorporated with TM complex
units via TM-Te bonds. Compound F contains fivefold coordinated [Zn(atep)]2+
cations and zigzag [Hg5Te124-]n polymeric anion. The [Hg5Te124-]n anion is a new
species of the binary telluromercurates. It is built from [Hg4Te6] and
[HgTe2(Te4)] subunits via interconnectivity, which generates Hg3Te3 and Hg4Te4
rings in the structure. Compounds A-F are potential semiconductors with narrow
band gaps in the range of 0.96-1.09 eV. Photocatalytic investigation of Mn(II)
complexes show that they are photocatalytically active in the degradation of CV
under visible-light irradiation with the highest catalytic effective of cluster
compound C.
PMID- 28492321
TI - Superionic Behavior and Phase Transition in a Vanthoffite Mineral.
AB - Crystals of a Vanthoffite mineral, Na6Mn(SO4)4, grown from an aqueous solution,
belong to a monoclinic system, P21/c, Z = 2, at ambient temperature. Thermal
analysis indicates a phase transition at 455 degrees C, which was substantiated
by in situ variable-temperature powder X-ray diffraction. The structure is
orthorhombic (Pmmm) after the phase transition and reverts to the monoclinic
system upon cooling. Variable-temperature ionic conductivity measurements show a
significantly higher value (~10-2 S cm-1) beyond the phase transition
temperature.
PMID- 28492322
TI - Hydrogen-Induced Adsorption of Carbon Monoxide on the Gold Dimer Cation: A Joint
Experimental and DFT Investigation.
AB - It is demonstrated, using tandem mass spectrometry and radio frequency ion trap,
that the adsorption of a H atom on the gold dimer cation, Au2H+, prevents its
dissociation and allows for adsorption of CO. Reaction kinetics are measured by
employing a radio frequency ion trap, where Au2+ and CO interact for a given
reaction time. The effect of a hydrogen atom is evaluated by comparing reaction
rate constants measured for Au2+ and Au2H+. The theoretical results for the
adsorption of CO molecules and their reaction characteristics with Au2+ and Au2H+
are found to agree with the experimental findings. The joint investigations
provide insights into hydrogen atom adsorption effects and consequent reaction
mechanisms.
PMID- 28492325
TI - Theoretical Study of the Solvation Effect on the Reductive Reaction of Vinylene
Carbonate in the Electrolyte Solution of Lithium Ion Batteries.
AB - Carbon monoxide generation reaction of vinylene carbonate (VC) in the electrolyte
solution of lithium ion batteries (ethylene carbonate (EC) and 1.0 M LiClO4/EC)
is studied using the RISM-SCF-SEDD method, a hybrid methodology of statistical
mechanics for molecular liquids and quantum chemistry. The analytical treatment
of the solvent and lithium salt enables us to treat the complicated composition
of the solution such as the concentration of the salt which is difficult for the
methods based on the molecular dynamics (MD) simulation. The free energy profile
and solvation structure are discussed in order to clarify the effect of the
solvent, especially lithium salt on the reaction. The lithium salt strongly
stabilizes the system due to the electrostatic interaction compared with the
system in which the salt does not exist. The effect of the salt is especially
important for considering the ionization process of VC.
PMID- 28492323
TI - A Mixed-Ring Sandwich Complex from Unexpected Ring Contraction in [Re(eta6
C6H5Br)(eta6-C6R6)](PF6).
AB - The contraction of coordinated aromatic hydrocarbons is a rare reactivity pattern
in organometallic chemistry. We describe the conversion of a bromobenzene
coordinated to a ReI center into a cyclopentadienyl aldehyde. Under mildly
alkaline conditions, the expected phenol complex is formed with Re and 99Tc but
under strong basic conditions; ring contraction occurs in close to quantitative
yields for Re only. A mechanism for this unprecedented reaction is proposed based
on 1H and 2H NMR spectra and density functional theory calculations.
PMID- 28492324
TI - Selective 1H-1H Distance Restraints in Fully Protonated Proteins by Very Fast
Magic-Angle Spinning Solid-State NMR.
AB - Very fast magic-angle spinning (MAS > 80 kHz) NMR combined with high-field
magnets has enabled the acquisition of proton-detected spectra in fully
protonated solid samples with sufficient resolution and sensitivity. One of the
primary challenges in structure determination of protein is observing long-range
1H-1H contacts. Here we use band-selective spin-lock pulses to obtain selective
1H-1H contacts (e.g., HN-HN) on the order of 5-6 A in fully protonated proteins
at 111 kHz MAS. This approach is a major advancement in structural
characterization of proteins given that magnetization can be selectively
transferred between protons that are 5-6 A apart despite the presence of other
protons at shorter distance. The observed contacts are similar to those
previously observed only in perdeuterated proteins with selective protonation.
Simulations and experiments show the proposed method has performance that is
superior to that of the currently used methods. The method is demonstrated on GB1
and a beta-barrel membrane protein, AlkL.
PMID- 28492326
TI - Pd-Catalyzed Regioselective 1,2-Difunctionalization of Vinylarenes with Alkenyl
Triflates and Aryl Boronic Acids at Ambient Temperature.
AB - A Pd-catalyzed highly regioselective 1,2-difunctionalization of vinylarenes is
disclosed in which multisubstituted olefins are efficiently and conveniently
constructed under ambient temperature with good compatibility and a broad
substrate scope. Notably, a quarternary carbon center could be readily built up
from 1,1-disubstituted styrenes, which are big challenges in the previous
methods.
PMID- 28492327
TI - Versatile Methodology for Glycosurfaces: Direct Ligation of Nonderivatized
Reducing Saccharides to Poly(pentafluorophenyl acrylate) Grafted Surfaces via
Hydrazide Conjugation.
AB - In this work, we report a convenient and versatile strategy for surface-grafted
glycopolymer constructs with the goal of surface modification that controls the
chemical presentation and grafting density of carbohydrate side chains. This
approach employs a difunctional hydrazine linker, chemically modified to an
active ester containing poly(pentafluorophenyl acrylate) grafted scaffold, to
conjugate a variety of saccharides through the reducing end. The successive
conjugation steps are carried out under mild conditions and yield high surface
densities of sugars, as high as 4.8 nmol.cm-2, capable of multivalency, with an
intact structure and retained bioactivity. We also demonstrate that this
glycosylated surface can bind specific lectins according to the structure of its
pendant carbohydrate. To demonstrate bioactivity, this surface platform is used
to study the binding events of a human respiratory tract pathogen, Mycoplasma
pneumoniae, on surfaces conjugated with sialylated sugars.
PMID- 28492328
TI - Inhibition of Radiolytic Molecular Hydrogen Formation by Quenching of Excited
State Water.
AB - Comparison of experimental measurements of the yield of molecular hydrogen
produced in the gamma radiolysis of water and aqueous nitrate solutions with
predictions of a Monte Carlo track chemistry model shows that the nitrate anion
scavenging of the hydrated electron, its precursor, and hydrogen atom cannot
account for the observed decrease in the yield at high nitrate anion
concentrations. Inclusion of the quenching of excited states of water (formed by
either direct excitation or reaction of the water radical cation with the
precursor to the hydrated electron) by the nitrate anion into the reaction scheme
provides excellent agreement between the stochastic calculations and experiment
demonstrating the existence of this short-lived species and its importance in
water radiolysis. Energy transfer from the excited states of water to the nitrate
anion producing an excited state provides an additional pathway for the
production of nitrogen containing products not accounted for in traditional
radiation chemistry scenarios. Such reactions are of central importance in
predicting the behavior of liquors common in the reprocessing of spent nuclear
fuel and the storage of highly radioactive liquid waste prior to vitrification.
PMID- 28492329
TI - Preserved Transmembrane Segment Topology, Structure, and Dynamics in Disparate
Micellar Environments.
AB - Detergent micelles are frequently employed as membrane mimetics for solution
state membrane protein nuclear magnetic resonance spectroscopy. Here we compare
topology, structure, ps-ns time-scale dynamics, and hydrodynamics of a model
protein with one transmembrane (TM) segment (residues 1-55 of the apelin
receptor, APJ, a G-protein-coupled receptor) in three distinct, commonly used
micellar environments. In each environment, two solvent-protected helical
segments connected by a solvent-exposed kink were observed. The break in helical
character at the kink was maintained in a helix-stabilizing fluorinated alcohol
environment, implying that this structural feature is inherent. Molecular
dynamics simulations also substantiate favorable self-assembly of compact protein
micelle complexes with a more dynamic, solvent-exposed kink. Despite the observed
similarity in TM segment behavior, micelle-dependent differences were clear in
the structure, dynamics, and compactness of the 30-residue, extramembrane N
terminal tail of the protein. This would affect intermolecular interactions and,
correspondingly, the functional state of the membrane protein.
PMID- 28492330
TI - Synthesis and Properties of Conjugated Macrocycles Containing 2,7-Bis(2-thienyl)
9H-fluoren-9-one Units.
AB - Synthetic pathways to conjugated macrocycles containing one, two, or three 2,7
bis(2-thienyl)-9H-fluoren-9-one (TFOT) units in the macrocyclic frameworks
bearing 10, 16, or 24 aromatic units were developed. The Diels-Alder reaction
between (E,E)-1-(5-bromo-2-thienyl)-4-(5-iodo-2-thienyl)-1,3-butadiene and
dimethyl acetylenedicarboxylate produced the key Diels-Alder adduct for the
subsequent macrocyclic ring formation. UV-vis and fluorescence spectra of the
TFOT-containing molecules were recorded, and their electrochemical properties
were investigated by cyclic and differential pulse voltammetry.
Solvatofluorochromic properties were observed for the TFOT-containing molecules.
PMID- 28492331
TI - High-Throughput Screening To Identify Potent and Specific Inhibitors of Microbial
Sulfate Reduction.
AB - The selective perturbation of complex microbial ecosystems to predictably
influence outcomes in engineered and industrial environments remains a grand
challenge for geomicrobiology. In some industrial ecosystems, such as oil
reservoirs, sulfate reducing microorganisms (SRM) produce hydrogen sulfide which
is toxic, explosive, and corrosive. Despite the economic cost of sulfidogenesis,
there has been minimal exploration of the chemical space of possible inhibitory
compounds, and very little work has quantitatively assessed the selectivity of
putative souring treatments. We have developed a high-throughput screening
strategy to identify potent and selective inhibitors of SRM, quantitatively
ranked the selectivity and potency of hundreds of compounds and identified
previously unrecognized SRM selective inhibitors and synergistic interactions
between inhibitors. Zinc pyrithione is the most potent inhibitor of
sulfidogenesis that we identified, and is several orders of magnitude more potent
than commonly used industrial biocides. Both zinc and copper pyrithione are also
moderately selective against SRM. The high-throughput (HT) approach we present
can be readily adapted to target SRM in diverse environments and similar
strategies could be used to quantify the potency and selectivity of inhibitors of
a variety of microbial metabolisms. Our findings and approach are relevant to
efforts to engineer environmental ecosystems and also to understand the role of
natural gradients in shaping microbial niche space.
PMID- 28492332
TI - Cellular Fates of Manganese(II) Pentaazamacrocyclic Superoxide Dismutase (SOD)
Mimetics: Fluorescently Labeled MnSOD Mimetics, X-ray Absorption Spectroscopy,
and X-ray Fluorescence Microscopy Studies.
AB - Manganese(II) pentaazamacrocyclic complexes (MnPAMs) can act as small-molecule
mimics of manganese superoxide dismutase (MnSOD) with potential therapeutic
application in conditions linked to oxidative stress. Previously, the in vitro
mechanism of action has been determined, their activity has been demonstrated in
cells, and some representatives of this class of MnSOD mimetics have entered
clinical trials. However, MnPAM uptake, distribution, and metabolism in cells are
largely unknown. Therefore, we have used X-ray fluorescence microscopy (XFM) and
X-ray absorption spectroscopy (XAS) to study the cellular fate of a number of
MnPAMs. We have also synthesized and characterized fluorescently labeled (pyrene
and rhodamine) manganese(II) pyane [manganese(II) trans-2,13-dimethyl-3,6,9,12,18
pentaazabicyclo[12.3.1]octadeca-1(18),14,16-triene] derivatives and investigated
their utility for cellular imaging of MnPAMs. Their SOD activity was determined
via a direct stopped-flow technique. XFM experiments show that treatment with
amine-based manganese(II) pyane type pentaazamacrocycles leads to a 10-100-fold
increase in the overall cellular manganese levels compared to the physiological
levels of manganese in control cells. In treated cells in general, manganese was
distributed throughout the cell body, with a couple of notable exceptions. The
lipophilicity of the MnPAMs, examined by partitioning in octanol-buffer system,
was a good predictor of the relative cellular manganese levels. Analysis of the
XAS data of treated cells revealed that some fraction of amine-based MnPAMs taken
up by the cells remained intact, with the rest transformed into SOD-active
manganese(II) phosphate. Higher phosphate binding constants, determined from the
effect of the phosphate concentration on in vitro SOD activity, were associated
with more extensive metabolism of the amine-based MnPAMs to manganese(II)
phosphate. In contrast, the imine-based manganese(II) pydiene complex that is
prone to hydrolysis was entirely decomposed after uptake and free manganese(II)
was oxidized to a manganese(III) oxide type species, in cytosolic compartments,
possibly mitochondria. Complex stability constants (determined for some of the
MnPAMs) are less indicative of the cellular fate of the complexes than the
corresponding phosphate binding constants.
PMID- 28492333
TI - Self-Assembly of Amphiphilic Biotransesterified beta-Cyclodextrins:
Supramolecular Structure of Nanoparticles and Surface Properties.
AB - A series of beta-cyclodextrin (betaCD) amphiphilic derivatives with varying
degrees of substitution were prepared by acylating betaCDs on their secondary
face using thermolysin to catalyze the transesterification. After dissolution in
acetone, the betaCD-Cn derivatives (n = 8, 10, 12, 14) were nanoprecipitated in
water, where they self-organized into structured particles that were
characterized using cryo-transmission electron microscopy (cryo-TEM) images and
small-angle X-ray scattering (SAXS) data. Two types of morphologies and
ultrastructures were observed depending on the total degree of substitution (TDS)
of the parent derivative. The molecules with TDS < 5 formed nanospheres with a
multilamellar organization, whereas those with TDS > 5 self-assembled into barrel
like (n = 8, 10, 12) or more tortuous (n = 14) particles with a columnar inverse
hexagonal structure. In particular, faceted betaCD-C14 particles (TDS = 7)
appeared to be composed of several domains with different orientations that were
separated by sharp interfaces. Ultrastructural models were proposed on the basis
of cryo-TEM images and the analysis of the contrast distribution in different
projections of the lattice. Complementary compression isotherm experiments
carried out at the air-water interface also suggested that differences in the
molecular conformation of the series of derivatives existed depending on whether
TDS was lower or higher than 5.
PMID- 28492334
TI - Solid-Liquid Interface Thermal Resistance Affects the Evaporation Rate of
Droplets from a Surface: A Study of Perfluorohexane on Chromium Using Molecular
Dynamics and Continuum Theory.
AB - We study the role of solid-liquid interface thermal resistance (Kapitza
resistance) on the evaporation rate of droplets on a heated surface by using a
multiscale combination of molecular dynamics (MD) simulations and analytical
continuum theory. We parametrize the nonbonded interaction potential between
perfluorohexane (C6F14) and a face-centered-cubic solid surface to reproduce the
experimental wetting behavior of C6F14 on black chromium through the solid-liquid
work of adhesion (quantity directly related to the wetting angle). The thermal
conductances between C6F14 and (100) and (111) solid substrates are evaluated by
a nonequilibrium molecular dynamics approach for a liquid pressure lower than 2
MPa. Finally, we examine the influence of the Kapitza resistance on evaporation
of droplets in the vicinity of a three-phase contact line with continuum theory,
where the thermal resistance of liquid layer is comparable with the Kapitza
resistance. We determine the thermodynamic conditions under which the Kapitza
resistance plays an important role in correctly predicting the evaporation heat
flux.
PMID- 28492335
TI - Energy-Storage Applications for a pH Gradient between Two Benzimidazole-Ligated
Ruthenium Complexes That Engage in Proton-Coupled Electron-Transfer Reactions in
Solution.
AB - The judicious selection of pairs of benzimidazole-ligated ruthenium complexes
allowed the construction of a rechargeable proton-coupled electron-transfer
(PCET)-type redox battery. A series of ruthenium(II) and -(III) complexes were
synthesized that contain substituted benzimidazoles that engage in PCET
reactions. The formation of intramolecular Ru-C cyclometalation bonds stabilized
the resulting ruthenium(III) complexes, in which pKa values of the imino N-H
protons on the benzimidazoles are usually lower than those for the corresponding
ruthenium(II) complexes. As a proof-of-concept study for a solution redox battery
based on such PCET reactions, the charging/discharging cycles of several pairs of
ruthenium complexes were examined by chronopotentiometry in an H-type device with
half-cells separated by a Nafion membrane in unbuffered CH3CN/H2O (1/1, v/v)
containing 0.1 M NaCl. During the charging/discharging cycles, the pH value of
the solution gradually changed accompanied by a change of the open-circuit
potential (OCP). The changes for the OCP and pH value of the solution in the
anodic and cathodic half-cells were in good agreement with the predicted values
from the Pourbaix diagrams for the pairs of ruthenium complexes used.
Accordingly, the careful selection of pairs of ruthenium complexes with a
sufficient potential gradient and a suitably large pKa difference is crucial: the
charge generated between the two ruthenium complexes changes the OCP and the pH
difference between the two cells in an unbuffered solution, given that the PCET
reactions occur at both electrodes and that discharging leads to the original
state. Because the electric energy is stored as a pH gradient between the half
cells, new possibilities for PCET-type rocking-chair redox batteries arise.
PMID- 28492336
TI - Development of indication criteria for preoperative examination in lung cancer.
AB - Background Systemic examination for distant metastases is generally recommended
for all lung cancer patients. However, this approach rarely detects distant
metastases in typically resectable cT1-2N0 non-small-cell lung cancer. The aim of
this study was to identify factors associated with distant metastases and develop
indication criteria for preoperative systemic examination in patients with cT1
2N0 non-small-cell lung cancer, with a particular focus on computed tomography
imaging of primary lesions. Methods We retrospectively reviewed non-small-cell
lung cancer patients treated at our institute between 2005 and 2013. Data were
extracted and compared between two groups: patients diagnosed as cT1-2N0M0 who
underwent complete resection (M0 group, n = 1530) and those diagnosed as cT1
2N0M1b who received systemic chemotherapy (M1 group, n = 26). Results The median
age at diagnosis was significantly lower in the M1 group ( p = 0.015). Although
carcinoembryonic antigen levels were significantly higher in the M1 group ( p <
0.001), 42% had normal levels. Tumor diameters in lung and mediastinal windows on
chest computed tomography were significantly larger, and the proportion
(mediastinal/lung window tumor diameter ratio) was higher in the M1 group ( p <
0.001). All 26 patients in the M1 group had a tumor diameter >15 mm and
mediastinal/lung window ratio >0.75. Conclusions Preoperative systemic
examination is not necessary in cT1-2N0 non-small-cell lung cancer patients when
tumor diameters are <=15 mm and mediastinal/lung window ratios are <=0.75.
According to these criteria, systemic examinations would have been reduced by 40%
in our cohort.
PMID- 28492337
TI - Amplatzer vascular plug in occlusion of a pulmonary arteriovenous malformation.
AB - Pulmonary arteriovenous malformation is a rare condition with abnormal
communication of the pulmonary artery with the pulmonary vein. It is associated
with significant morbidity and mortality when patients develop complications.
Patients with symptomatic pulmonary arteriovenous malformation should be
considered for intervention. We describe the case of a 54-year-old woman with a
large right pulmonary arteriovenous malformation who presented with right chest
pain due to hemothorax. She underwent successful embolotherapy with an Amplatzer
plug.
PMID- 28492338
TI - Headache as a presenting symptom of glioma: A cross-sectional study.
AB - Objective The objective of this study was to analyse the prevalence and the
clinical features of headache as a presenting symptom of glioma. Methods We
interviewed 527 consecutive adult patients with histologically confirmed glioma,
admitted to the Regina Elena National Cancer Institute between 2010 and 2015. We
defined four headache phenotypes: Tension-type-like headache (TTH), migraine-like
headache, worsening of a pre-existing headache (WPH) and classic brain tumour
headache (BTH). Logistic regression analysis was carried out to investigate
potential risk factors for headache at presentation of glioma. Results 12.5% (n =
66) of patients with glioma indicated headache as a presenting symptom of their
disease. Of these, 31 patients (47%) had TTH, while BTH and WPH were reported by
28 (42%) and seven (11%) patients, respectively. We did not find any case of
migraine-like headache. Infratentorial ( p = 0.038) and right-sided tumours ( p =
0.013) were more frequently associated with the presence of headache at onset.
Patients with TTH were older than patients with BTH and WPH ( p = 0.035). BTH was
less frequently associated with other neurological signs ( p < 0.0001). The
multivariate logistic regression analysis showed the localization of the brain
tumour in the left hemisphere to be a protective factor for the development of
headache. Conclusions Our study includes a very large series of patients with
glioma, providing a description of headache phenotype at first presentation of
disease and investigating possible factors that may influence the clinical
features of headache.
PMID- 28492339
TI - Venetoclax for the treatment of patients with chronic lymphocytic leukemia.
AB - Venetoclax is a potent, selective inhibitor of BCL-2, a key regulator of the
intrinsic pathway of apoptosis. In preclinical studies, venetoclax bound to BCL-2
with high affinity and rapidly induced apoptosis in chronic lymphocytic leukemia
(CLL) cells. In early-phase clinical trials in CLL, venetoclax treatment led to
tumor lysis syndrome in some patients with a large tumor burden, but this risk
was subsequently mitigated by a revised study design that included lower initial
dosing with intrapatient dose ramp up and close tumor lysis syndrome monitoring
and prophylaxis. Other toxicities, such as neutropenia and gastrointestinal
adverse events, were manageable. Venetoclax monotherapy resulted in durable and
deep responses in patients with relapsed, refractory CLL, including for those
with deletion 17p, leading to the approval of venetoclax by the US FDA for
relapsed or refractory deletion 17p CLL, and recently to additional approvals in
Europe and Canada. Trials also suggest that venetoclax induces deeper and more
durable responses when used in combination with rituximab, and combination
studies with other agents are ongoing. Phase III trials are also underway, and
will provide data on the efficacy and safety of venetoclax in combination with
monoclonal antibodies and targeted therapies in larger patient populations.
PMID- 28492340
TI - Alterations of zinc homeostasis in response to Cryptococcus neoformans in a
murine macrophage cell line.
AB - AIM: To evaluate alterations of zinc homeostasis in macrophages exposed to
Cryptococcus neoformans. Materials & methods: Using a fluorescent zinc probe
based flow cytometry and atomic absorption spectrometry, zinc levels were
evaluated in J774.A1 cell lines exposed to C. neoformans H99 cells. The
transcription profile of macrophage zinc related homeostasis genes -
metallothioneins and zinc transporters (ZnTs) of the SLC30 and SLC39 (Zrt-Irt
protein) families - was analyzed by quantitative PCR. RESULTS: Macrophage
intracellular labile zinc levels decreased following exposure to C. neoformans. A
significant decrease in transcription levels was detected in specific ZnTs from
both the Zrt-Irt-protein and ZnT families, especially 24 h after infection.
CONCLUSION: These findings suggest that macrophages may exhibit zinc depletion in
response to C. neoformans infection.
PMID- 28492342
TI - Social, cognitive, behavioural and neighbourhood characteristics associated with
sedentary time in men and women living in deprived neighbourhoods.
AB - Multiple individual and neighbourhood characteristics are theorised to influence
adult sedentary behaviour. The aim of this study was to examine associations
between individual and neighbourhood-level characteristics in 40 deprived
neighbourhoods in London, UK. A cross-sectional design was utilised with baseline
data from the Well London Cluster Randomised Controlled Trial in 40 deprived
neighbourhoods in London. Multilevel linear regression was used to examine
associations between individual characteristics (measured by household survey),
neighbourhood characteristics (neighbourhood audit, GIS and routinely available
datasets) and sedentary behaviour (sitting time). Individual-level positive
mental well-being and health behaviours were associated with sedentary time.
Individual-level social networks were associated with decreased sedentary time in
men and increased sedentary time in women. Neighbourhood-level measures of social
networks and perceived neighbourhood quality were associated with reduced
sedentary time. Fifteen per cent of the variance in sedentary time was
attributable to differences at the neighbourhood level (intra-class correlation
coefficient = 0.15). These findings suggest that social networks at the
individual and neighbourhood levels, collective perceptions of neighbourhood
quality, individual-level positive mental well-being and other health behaviours
may be important components of interventions developed to reduce sedentary time
in deprived populations.
PMID- 28492341
TI - Implications of neurovascular uncoupling in functional magnetic resonance imaging
(fMRI) of brain tumors.
AB - Functional magnetic resonance imaging (fMRI) serves as a critical tool for
presurgical mapping of eloquent cortex and changes in neurological function in
patients diagnosed with brain tumors. However, the blood-oxygen-level-dependent
(BOLD) contrast mechanism underlying fMRI assumes that neurovascular coupling
remains intact during brain tumor progression, and that measured changes in
cerebral blood flow (CBF) are correlated with neuronal function. Recent
preclinical and clinical studies have demonstrated that even low-grade brain
tumors can exhibit neurovascular uncoupling (NVU), which can confound
interpretation of fMRI data. Therefore, to avoid neurosurgical complications, it
is crucial to understand the biophysical basis of NVU and its impact on fMRI.
Here we review the physiology of the neurovascular unit, how it is remodeled, and
functionally altered by brain cancer cells. We first discuss the latest findings
about the components of the neurovascular unit. Next, we synthesize results from
preclinical and clinical studies to illustrate how brain tumor induced NVU
affects fMRI data interpretation. We examine advances in functional imaging
methods that permit the clinical evaluation of brain tumors with NVU. Finally, we
discuss how the suppression of anomalous tumor blood vessel formation with
antiangiogenic therapies can "normalize" the brain tumor vasculature, and
potentially restore neurovascular coupling.
PMID- 28492345
TI - The Focinator v2-0 - Graphical Interface, Four Channels, Colocalization Analysis
and Cell Phase Identification.
AB - The quantitative analysis of foci plays an important role in various cell
biological methods. In the fields of radiation biology and experimental oncology,
the effect of ionizing radiation, chemotherapy or molecularly targeted drugs on
DNA damage induction and repair is frequently performed by the analysis of
protein clusters or phosphorylated proteins recruited to so called repair foci at
DNA damage sites, involving for example gamma-H2A.X, 53BP1 or RAD51. We recently
developed "The Focinator" as a reliable and fast tool for automated quantitative
and qualitative analysis of nuclei and DNA damage foci. The refined software is
now even more user-friendly due to a graphical interface and further features.
Thus, we included an R-script-based mode for automated image opening, file
naming, progress monitoring and an error report. Consequently, the evaluation no
longer required the attendance of the operator after initial parameter
definition. Moreover, the Focinator v2-0 is now able to perform multi-channel
analysis of four channels and evaluation of protein-protein colocalization by
comparison of up to three foci channels. This enables for example the
quantification of foci in cells of a specific cell cycle phase.
PMID- 28492343
TI - Multi-level risk factors associated with sex trading among women living with HIV
in Kazakhstan: A neglected key population.
AB - Little is known about the prevalence and risk factors associated with sex trading
among HIV-positive women. A total of 242 HIV-positive women were recruited in
five regions in Kazakhstan. These women completed a survey containing items on
socio-demographics, HIV stigma, intimate partner violence, and partner risk
behaviors. Multivariate regression was used to examine associations between risk
factors and sex trading after controlling for socio-demographic factors. Fifty
six (23.1%) women reported trading sex in the past 90 days. Women who reported
recent sex trading were more likely than women who did not trade sex in the past
90 days to experience intimate partner violence (adjusted odds ratio [AOR]: 2.25;
95% confidence interval [CI]: 1.08-4.73), to have been homeless in the past 90
days (AOR: 4.12; 95% CI: 1.19-14.29), and to know or suspect a male partner had a
sexually transmitted infection (AOR: 2.20; 95% CI: 1.07-4.53), had sex with
another partner (AOR: 4.53; 95% CI: 2.25-9.14), or injected drugs in the past
year (AOR: 3.31; 95% CI: 1.64-6.65). These findings underscore the need for
comprehensive HIV prevention and intervention programs that address the multi
level risk factors associated with sex trading for women infected with HIV.
PMID- 28492346
TI - Yoga Communities and Eating Disorders: Creating Safe Space for Positive
Embodiment.
AB - With adequate education and guidance, yoga communities, as part of the
therapeutic landscape in the 21st century, can play a significant role promoting
positive embodiment for those with, and at-risk for, eating disorders (EDs). To
do this, yoga teachers need to know how to create a body-positive community and
be able to recognize and respond to those at risk and struggling with EDs in
their communities. In order to address yoga teaching methods associated with EDs
and ED risk, broader conceptual approaches and specific practices associated with
positive embodiment are offered. These include the broader conceptual approaches
of: intentional inclusion and acceptance, experiential emphasis, supporting
positive embodiment and inquiry. Studio pragmatics are also detailed as related
to the body, breath, emotions, and community. Assessment, referral, and community
engagement are also addressed.
PMID- 28492344
TI - Andrographis paniculata Diterpenoids Protect against Radiation-Induced
Transformation in BALB/3T3 Cells.
AB - One of the most concerning side effects of exposure to radiation are the
carcinogenic risks. To reduce the negative effects of radiation, both
cytoprotective and radioprotective agents have been developed. However, little is
known regarding their potential for suppressing carcinogenesis. Andrographis
paniculata , a plant, with multiple medicinal uses that is commonly used in
traditional medicine, has three major constituents known to have cellular
antioxidant activity: andrographolide (AP1); 14-deoxy-11,12
didehydroandrographolide (AP3); and neoandrographolide (AP4). In our study, we
tested these elements for their radioprotective properties as well as their anti
neoplastic effects on transformation using the BALB/3T3 cell model. All three
compounds were able to reduce radiation-induced DNA damage. However, AP4 appeared
to have superior radioprotective properties compared to the other two compounds,
presumably by protecting mitochondrial function. The compound was able to
suppress radiation-induced cellular transformation through inhibition of STAT3.
Treatment with AP4 also reduced expressions of MMP-2 and MMP-9. These results
suggest that AP4 could be further studied and developed into an anti
transformation/carcinogenic drug as well as a radioprotective agent.
PMID- 28492347
TI - The soy-derived peptide Vglycin inhibits the growth of colon cancer cells in
vitro and in vivo.
AB - Vglycin, a novel natural polypeptide isolated from pea seeds, possesses
antidiabetic properties. Our previous studies have shown that Vglycin can induce
the differentiation of human colon adenocarcinoma cells. We aimed to determine
the anticancer activity of Vglycin against colon cancer cells and to elucidate
related apoptosis-inducing mechanisms. Treatment with purified Vglycin
significantly reduced growth, viability, and colony formation of CT-26, SW480,
and NCL-H716 colon cancer cells in a dose-dependent manner while down-regulating
the expression of proliferating cell nuclear antigen. Mouse xenograft studies
showed a 38% inhibition of colon cancer growth in mice treated with Vglycin (20
mg/kg/day) at day 21. Furthermore, the potential mechanisms involved in Vglycin
induced cell apoptosis were examined using cell cycle studies, ultrastructural
examination, as well as apoptosis-associated pathway analysis. The results showed
that Vglycin significantly promoted apoptosis and G1/S phase cell cycle arrest.
As revealed by Western blot, the expression of CDK2 and Cyclin D1 was down
regulated in all three Vglycin-treated colon cancer cells, indicating that the
CDK2/Cyclin D1 cell cycle pathway involved in the initiation and progression of
colon cancer. Moreover, the inhibition of Vglycin-induced cell proliferation in
colon cancer cells was accompanied by alteration of the expression levels of the
apoptosis-related proteins Bax, Bcl-2 and Mcl-1, and an increase of caspase-3
activity. Together, our results suggest that Vglycin may be another plant-derived
peptide that suppresses colon cancer, supporting the continued investigation of
Vglycin as therapeutic agent for colon cancer. Impact statement The antidiabetic
properties and the capability of inducing differentiation of human colon
adenocarcinoma cells of Vglycin have been reported in our previous studies.
However, the anticancer potential of Vglycin on colon cancer cells and its
possible related mechanisms were still unknown. In this study, we found that
Vglycin could reduce growth, viability, and colony formation or colony size of CT
26, SW480, and NCL-H716 colon cancer cells. Moreover, Vglycin decreased tumor
volume by 38% in xenograft mice transplanted with CT-26 cells. The mechanisms of
these phenomena may be due to the down-regulated CDK2 and Cyclin D1, G1/S phase
cell cycle arrest, and the dysregulated expression of Bax, Bcl-2, and Mcl-1. The
findings highlight the anticancer potential of Vglycin against colon cancer
cells, and suggest Vglycin may be another colon cancer potential suppressive
component of plant-derived peptides.
PMID- 28492348
TI - Culture of human cells in experimental units for spaceflight impacts on their
behavior.
AB - Because space missions produce pathophysiological alterations such as
cardiovascular disorders and bone demineralization which are very common on
Earth, biomedical research in space is a frontier that holds important promises
not only to counterbalance space-associated disorders in astronauts but also to
ameliorate the health of Earth-bound population. Experiments in space are complex
to design. Cells must be cultured in closed cell culture systems (from now
defined experimental units (EUs)), which are biocompatible, functional, safe to
minimize any potential hazard to the crew, and with a high degree of automation.
Therefore, to perform experiments in orbit, it is relevant to know how closely
culture in the EUs reflects cellular behavior under normal growth conditions. We
compared the performances in these units of three different human cell types,
which were recently space flown, i.e. bone mesenchymal stem cells, micro- and
macrovascular endothelial cells. Endothelial cells are only slightly and
transiently affected by culture in the EUs, whereas these devices accelerate
mesenchymal stem cell reprogramming toward osteogenic differentiation, in part by
increasing the amounts of reactive oxygen species. We conclude that cell culture
conditions in the EUs do not exactly mimic what happens in a culture dish and
that more efforts are necessary to optimize these devices for biomedical
experiments in space. Impact statement Cell cultures represent valuable
preclinical models to decipher pathogenic circuitries. This is true also for
biomedical research in space. A lot has been learnt about cell adaptation and
reaction from the experiments performed on many different cell types flown to
space. Obviously, cell culture in space has to meet specific requirements for the
safety of the crew and to comply with the unique environmental challenges. For
these reasons, specific devices for cell culture in space have been developed. It
is important to clarify whether these alternative culture systems impact on cell
performances to allow a correct interpretation of the data.
PMID- 28492350
TI - The underestimated role of somatostatin analogs in the NETTER-1 trial.
PMID- 28492349
TI - A novel compressive stress-based osteoarthritis-like chondrocyte system.
AB - Mechanical stress damage and insufficient self-repair can contribute to
osteoarthritis (OA) in the affected joint. As the effects of stress on
chondrocyte metabolism can regulate cartilage homeostasis, the specific stress
response condition is therefore a key to the generation of an OA disease model.
We aimed to produce a specific stress- and cell-based OA model after evaluating
the metabolic responses of chondrocytes in response to a series of static and
cyclic compression stressors. A static load exceeding 40 psi initiated
extracellular matrix (ECM) degradation through a decrease in the sulphated
glycosaminoglycan (GAG) content, upregulation of catabolic matrix
metalloproteinase (MMP)-13 encoding gene expression, and downregulation of the
ECM-related aggrecan and type II collagen encoding genes within 24 h. Indicators
of pro-inflammatory events and oxidative stress were found to correlate with
increased IL-6 expression and reactive oxygen species (ROS) production,
respectively. However, chondrocytes stimulated by moderate cyclic loading (30-40
psi) exhibited increased ECM-related gene expression without significant changes
in catabolic and pro-inflammatory gene expression. BMP-7 expression increased at
cyclic loading levels above 30-60 psi. These results demonstrated that static
compression exceeding 60 psi is sufficient to produce OA-like chondrocytes that
exhibit signs of ECM degradation and inflammation. These OA-like chondrocytes
could therefore be used as a novel cell-based drug screening system. Impact
statement The lack of an effective treatment for osteoarthritis (OA) reflects the
great need for alternative therapies and drug discovery. Disease models can be
used for early-stage compound screening and disease studies. Chondrocytes are
solely responsible for the maintenance of the articular cartilage extracellular
matrix. Our strategy involved the generation of a cell-based model of OA, a more
readily studied disease. Instead of using animal cartilage explants, we
incorporated isolated porcine chondrocytes with hydrogel to form three
dimensional assemblies. We could identify the specific magnitude-dependent
metabolic responses of chondrocytes by applying a series of static and cyclic
compression, and therefore successfully generated a novel OA-like cell-based
model for drug screening.
PMID- 28492351
TI - mesT, a unique epoxide hydrolase, is essential for optimal growth of
Mycobacterium tuberculosis in the presence of styrene oxide.
AB - AIM: mesT of Mycobacterium tuberculosis, a hypothetical/putative epoxide
hydrolase, is predicted to convert toxic epoxides to the more water-soluble and
less toxic diols. Detailed characterization of the protein was carried out.
RESULTS: mesT demonstrated esterase as well as epoxide hydrolase activity. It was
membrane bound and was upregulated under hypoxic conditions. The enzyme was able
to degrade styrene oxide. The presence of antisense against this gene resulted in
the inhibition of in vitro bacterial growth/survival in the presence of styrene
oxide. Conclusion & future perspective: We demonstrated that mesT possessed
epoxide hydrolase activity and styrene oxide might be its physiological
substrate. Inhibition of mesT reduced the growth of the bacteria in presence of
styrene oxide and its expression under hypoxic condition suggested its role in
intracellular survival of bacteria.
PMID- 28492352
TI - The Physiological Incubation Biosimulator (PIBS): An Improved Ex Vivo
Experimental Setup for the Mechanical Stability of Biological Sealants in
Surgical Procedures.
AB - BACKGROUND: Tissue-bound fibrin sealants are used in a wide array of surgical
procedures. The microenvironmental interaction between sealant and application
site is often poorly evaluated due to a lack of suitable experimental models.
METHODS: A physiological incubation biosimulator (PIBS) was developed to test
biological sealants in an ex vivo setup under physiological conditions comparable
to the microenvironment at application site (temperature, humidity, pressure).
PIBS was validated by a study on the effectiveness of TachoSil for leak closure
at pancreatic resection sites. Defined defects in a thoracic membrane of porcine
origin were sealed by TachoSil. Integrity of the sealing was tested in the
presence of active pancreatic fluid over 60 minutes. Heat-inactivated pancreatic
fluid and electrolyte solution served as controls. The time to leakage was
recorded and experimental groups were analyzed by Kaplan-Meier analysis. RESULTS:
PIBS produced reliable results. TachoSil lead to a leakage rate of 96% after
incubation with active pancreatic fluid (p = 34), which was significantly higher
compared with heat-inactivated pancreatic fluid (p = 34, 52%) or electrolyte
solution (p = 20, 19%). CONCLUSION: PIBS is an effective tool to evaluate
microenvironmental effects on the adhesive strength of biomaterials. Tissue
sealing effect of TachoSil is diminished in a "pancreatic" microenvironment rich
with pancreatic enzymes. Our results might therefore explain the reason of the
findings of randomized controlled trials recently published on this subject.
PMID- 28492353
TI - Laparoscopy Using Room Air Insufflation in a Rural African Jungle Hospital: The
Bongolo Hospital Experience, January 2006 to December 2013.
AB - INTRODUCTION: Carbon dioxide is the standard insufflation gas for laparoscopy.
However, in many areas of the world, bottled carbon dioxide is not available.
Laparoscopy offers advantages over open surgery and has been practiced using
filtered room air insufflation since 2006 at Bongolo Hospital in Gabon, Africa.
OBJECTIVE: Our primary goal was to evaluate the safety of room air insufflation
related to intraoperative and postoperative complications. Our secondary aim was
to review the types of cases performed laparoscopically at our institution.
METHODS: This retrospective review evaluates laparoscopic cases performed at
Bongolo Hospital between January 2006 and December 2013. Demographic and
perioperative information for patients undergoing laparoscopic procedures was
collected. Insufflation was achieved using a standard, oil-free air compressor
using filtered air and a standard insufflation regulator. RESULTS: A total of 368
laparoscopic procedures were identified within the time period. The majority of
cases were gynecologic (43%). There was a 2% (8/368) complication rate with one
perioperative death. The 2 complications related to insufflation were episodes of
hypotension responsive to standard corrective measures. No intracorporeal
combustion events were observed in any cases in which the use of diathermy and
room air insufflation were combined. The other complications and the death were
unrelated to the use of insufflation with air. CONCLUSION: Insufflation
complications with room air occurred in our study. However, the complications
related to insufflation with room air in our study were no different than those
described in the literature using carbon dioxide. As room air is less costly than
carbon dioxide and readily available, confirming the safety of room air
insufflation in prospective studies is warranted. Room air appears to be safe for
establishing and maintaining pneumoperitoneum, making laparoscopic surgery more
accessible to patients in low-resource settings.
PMID- 28492354
TI - Experimental Evaluation of the Optimal Suture Pattern With a Flexible Endoscopic
Suturing System.
AB - BACKGROUND: The ability to perform reliable, secure endoluminal closure of the
gastrointestinal tract wall, is a prerequisite to support the progress of the
emerging field of endoluminal surgery. Along with advanced clipping systems,
flexible endoscopic suturing devices are commercially available. Current systems
can replicate traditional surgical suturing patterns in the endoluminal
environment. The aim of this study was to evaluate the optimal endoluminal
suturing technique using a flexible endoscopic suturing device. MATERIALS AND
METHODS: Procedures were performed on bench-top simulators containing 20
explanted porcine stomachs. A standardized 3-cm full-thickness incision was
created on the anterior wall of each stomach using monopolar cautery. The
gastrotomy was closed endoscopically using an over-the-scope suturing device
(OverStitch, Apollo Endosurgery; Austin, TX). Three different techniques were
used: single stitches, figure-of-8 pattern, and running suture. Material
consumption and operation time were recorded and bursting pressure measurement of
the closure was performed. RESULTS: No statistically significant differences were
identified in suturing time. Suturing time (minutes) was slightly shorter with
the figure-of-8 technique (41.14 +/- 4.6) versus interrupted (45.75 +/- 1.1)
versus continuous (51.44 +/- 10.0), but the difference was not statistically
significant. The number of sutures required was greater in the interrupted group.
No significant difference was found in the burst pressure (mm Hg): figure-of-8
(45.85 +/- 26.2) versus interrupted (30.5 +/- 22.89) versus continuous (32.0 +/-
26.5). In the figure-of-8 group, 85.5% of cases were leakproof above 30 mm Hg,
while in the other groups only 50% of cases were so. CONCLUSION: A figure-of-8
suturing pattern seems to be the preferable suturing technique with the
endoscopic suturing device.
PMID- 28492355
TI - Experimental Procedure of Compression Anastomosis Using Fragmented Rings: A
Porcine Model.
AB - BACKGROUND: Compression anastomosis has been recently abandoned because of a
nonsuperiority compared to stapling anastomosis. Nonremoval of the rings has
frequently been reported and this technique does not support a routine use. The
aim of this experimental study was to assess the feasibility of anastomosis using
compression with a device consisting of fragmented rings. METHODS: A new
compression device, the "Anastocom," was compared to standard double-stapled
colocolonic anastomosis in 2 groups of 8 pigs. In each group, colocolonic
anastomosis was performed with a circular stapler (DST Series EEA Staplers) in 4
pigs and with the Anastocom device for the other 4 pigs. RESULTS: The anastomotic
rings were expelled between postoperative day 7 and day 13 from the 4 animals
sacrificed at day 30. The anastomosis was clean and intact in all pigs. After
sacrifice, there was no difference in the bursting pressure at day 7 ( P = .226)
or at day 30 ( P = .885) between the 2 types of anastomosis. After sacrifice at
day 7, the mean bursting pressure values for the Anastocom and EEA anastomoses
were 128.6 mm Hg (range 119-143 mm Hg) and 218.9 mm Hg (range 84-240 mm Hg),
respectively. After sacrifice at day 30, the mean bursting pressure values for
the Anastocom and EEA anastomoses were 111 mm Hg (range 59-234 mm Hg) and 105 mm
Hg (range 81-130 mmHg), respectively. CONCLUSION: No bowel obstruction was
observed with Anastocom. This fragmentation mechanism should better prevent
nonexpulsion compared to basic compression anastomosis.
PMID- 28492356
TI - High-Frequency Irreversible Electroporation: Safety and Efficacy of Next
Generation Irreversible Electroporation Adjacent to Critical Hepatic Structures.
AB - Irreversible electroporation (IRE) is a nonthermal ablation modality employed to
induce in situ tissue-cell death. This study sought to evaluate the efficacy of a
novel high-frequency IRE (H-FIRE) system to perform hepatic ablations across, or
adjacent to, critical vascular and biliary structures. Using ultrasound guidance
H-FIRE electrodes were placed across, or adjacent to, portal pedicels, hepatic
veins, or the gall bladder in a porcine model. H-FIRE pulses were delivered (2250
V, 2-5-2 pulse configuration) in the absence of cardiac synchronization or
intraoperative paralytics. Six hours after H-FIRE the liver was resected and
analyzed. Nine ablations were performed in 3 separate experimental groups (major
vessels straddled by electrodes, electrodes placed adjacent to major vessels,
electrodes placed adjacent to gall bladder). Average ablation time was 290 +/- 63
seconds. No electrocardiogram abnormalities or changes in vital signs were
observed during H-FIRE. At necropsy, no vascular damage, coagulated-thermally
desiccated blood vessels, or perforated biliary structures were noted.
Histologically, H-FIRE demonstrated effective tissue ablation and uniform
induction of apoptotic cell death in the parenchyma independent of vascular or
biliary structure location. Detailed microscopic analysis revealed minor
endothelial damage within areas subjected to H-FIRE, particularly in regions
proximal to electrode insertion. These data indicate H-FIRE is a novel means to
perform rapid, reproducible IRE in liver tissue while preserving gross
vascular/biliary architecture. These characteristics raise the potential for long
term survival studies to test the viability of this technology toward clinical
use to target tumors not amenable to thermal ablation or resection.
PMID- 28492357
TI - Long-Term Effectiveness of Strattice in the Laparoscopic Closure of
Paraesophageal Hernias.
AB - Prosthetic reinforcement reduces the recurrence rate of large paraesophageal
hernias (PEH), but the use of synthetic or biosynthetic mesh in the repair
remains controversial. PEH repair has reported recurrence rates of 12% to 42%,
and primary repair of PEH by suture closure under tension is at high risk of
disruption. Synthetic mesh use in large PEH repair has shown to reduce recurrence
but can lead to problems including mesh erosion, ulceration, stricture, and
dysphagia. The objective of this study was to examine the long-term safety and
efficacy of Strattice biologic mesh, a porcine acellular dermal matrix, in crural
reinforcement of laparoscopic large PEH repair. Thirty-five patients with
symptomatic PEH (>5 cm) were consented to receive Strattice for PEH repair.
Patients were seen in clinic preoperatively, at surgery, and 2 weeks, 6 months,
and 12 months postoperatively. Patients were given a standard subjective reflux
test at each visit and a 12-month barium swallow X-ray to test for recurrence.
Hernia recurrence was documented in 14.3% of cases by the end of the 1-year
follow-up. Symptoms improved in 75% to 100% of patients by 6 months, and 33% to
100% of patients were still reporting symptom improvement at 12 months. Strattice
mesh in PEH repair results in similar outcomes to other absorbable meshes, and
the recurrence rate is within the 12% to 42% range of recurrences reported in
studies outside of our institution. The use of Strattice mesh in large PEH repair
had results similar to other biomaterial meshes and successfully decreased
patients' symptom scores through surgical intervention.
PMID- 28492358
TI - Absorbable Meshes in Inguinal Hernia Surgery: A Systematic Review and Meta
Analysis.
AB - PURPOSE: Absorbable meshes used in inguinal hernia repair are believed to result
in less chronic pain than permanent meshes, but concerns remain whether
absorbable meshes result in an increased risk of recurrence. The aim of this
study was to present an overview of the advantages and limitations of fully
absorbable meshes for the repair of inguinal hernias, focusing mainly on
postoperative pain and recurrence. METHODS: This systematic review with meta
analyses is based on searches in PubMed, Embase, Cochrane, and Psychinfo.
Included study designs were case series, cohort studies, randomized controlled
trials (RCTs), and non-RCTs. Studies had to include adult patients undergoing an
inguinal hernia repair with a fully absorbable mesh. RESULTS: The meta-analyses
showed no difference in recurrence rates (median 18 months follow-up) and chronic
pain rates (1 year follow-up) between absorbable- and permanent meshes. Crude
chronic pain rates for the RCTs were 2.1% for the absorbable meshes and 7.6% for
the permanent meshes. For the absorbable meshes, medial hernias were more
susceptible for recurrence compared with lateral hernias ( P < .0005). None of
the studies reported allergic reactions or other serious adverse events related
to the absorbable mesh. CONCLUSIONS: Patients with an absorbable mesh seem to
have less chronic pain following inguinal hernia surgery compared with permanent
meshes, without increased risk of recurrence.
PMID- 28492359
TI - Periodontitis and Endothelial Dysfunction: Periodontal Clinical Parameters and
Levels of Salivary Markers Interleukin-1beta, Tumor Necrosis Factor-alpha, Matrix
Metalloproteinase-2, Tissue Inhibitor of Metalloproteinases-2 Complex, and Nitric
Oxide.
AB - BACKGROUND: Periodontitis has been associated with a greater risk for
atherosclerotic cardiovascular disease (ACD). Endothelial dysfunction (ED) is a
parameter of early ACD, and its association with periodontitis has rarely been
investigated to date. The objective of this study is to evaluate the association
between periodontitis and ED by means of periodontal clinical parameters and
salivary markers interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha,
nitric oxide (NO), and matrix metalloproteinase (MMP)-2 and tissue inhibitor of
metalloproteinases (TIMP)-2 complex. METHODS: Forty-seven individuals were
divided into two groups: 1) 24 individuals with chronic periodontitis (CP); and
2) 23 individuals without CP. Periodontal examinations of bleeding on probing
(BOP), probing depth (PD), and clinical attachment level (CAL) were performed. ED
was evaluated by means of flow-mediated dilatation (FMD) of the brachial artery.
Salivary concentrations of IL-1beta, TNF-alpha, and MMP-2/TIMP-2 complex were
assessed using enzyme-linked immunosorbent assay. NO determination was based on
the reaction of Griess. RESULTS: Individuals with CP presented higher occurrence
of ED than individuals without CP (P = 0.03 after reactive hyperemia; P = 0.05
after sublingual nitrate). A significant association among the production of MMP
2/TIMP-2 complex with the presence of CP (P = 0.008) and periodontal parameters
PD, CAL, and BOP was identified. Concentration of salivary markers IL-1beta, TNF
alpha, and NO was similar in individuals with and without CP. A significant
positive correlation between NO and ED was also identified. CONCLUSIONS:
Periodontitis was positively associated with ED, expressed by a smaller
percentage of FMD of the brachial artery and higher salivary levels of MMP-2/TIMP
2 complex. Additionally, salivary levels of NO were significantly associated with
better functioning of the vascular endothelium.
PMID- 28492360
TI - Resveratrol Inhibits Periodontitis-Related Bone Loss in Rats Subjected to
Cigarette Smoke Inhalation.
AB - BACKGROUND: Alternative therapeutic approaches have been explored to modulate
host response to periodontal disease. Knowledge of new strategies to treat
periodontitis is particularly relevant in patients presenting augmented risk to
periodontitis, such as smokers. The aim of this study is to investigate the
impact of resveratrol (RESV) on progression of experimental periodontitis (EP) in
the presence of cigarette smoke inhalation (CSI). METHODS: Rats were assigned to
one of three groups: 1) CSI+RESV (n = 20); 2) CSI+placebo (n = 20); and 3) non
CSI (n = 20). CSI was initiated 1 week prior to initiation of RESV or placebo
administration (systemically for 30 days) and was continued until the end of the
study. EP was induced around the first mandibular and second maxillary molars
using ligatures. Specimens from the mandible were processed for morphometric and
microcomputed tomography examination of bone volume/levels. Gingival tissues
surrounding mandibular molars were collected for quantification of interleukin
(IL)-1beta, IL-4, IL-6, IL-17, and tumor necrosis factor-alpha using an assay
system. Additional analyses of immunoinflammatory mediator performance (T-helper
Type 17 [Th17]/Th2 and Th1/Th2 cell levels) were performed according to Th cell
responses in gingival tissues. Gingival tissues of maxillary molars were
subjected to real-time polymerase chain reaction for assessment of
osteoprotegrin, runt-related transcription factor-2, receptor activator of
nuclear factor-kappa B ligand (RANKL), sclerostin, and Dickkopf Wnt signaling
pathway inhibitor 1 levels. RESULTS: Higher linear alveolar bone loss (ABL) and
lower interradicular bone density were detected in ligated molars in the
CSI+placebo group (P <0.05). IL-4 level was the highest, and Th17/Th2 levels were
the lowest in RESV-treated rats compared with placebo rats (P <0.05). RESV
reduced expression of messenger RNA for RANKL in animals receiving CSI (P <0.05).
CONCLUSION: RESV inhibits EP and CSI-induced supporting ABL and has a beneficial
effect on osteo-immunoinflammatory markers.
PMID- 28492361
TI - Influence of rs2228570 on Transcriptional Activation by the Vitamin D Receptor in
Human Gingival Fibroblasts and Periodontal Ligament Cells.
AB - BACKGROUND: rs2228570 is the only known single nucleotide polymorphism of the
vitamin D receptor (VDR) that alters the protein structure. VDRs can be
distinguished using the restriction endonuclease FokI and accordingly divided
into three genotypes: FF, Ff, and ff. Influence of rs2228570 on transcriptional
activation by VDRs in human gingival fibroblasts (hGFs) and periodontal ligament
cells (hPDLCs) is investigated in this study. METHODS: From 15 donors, hGFs and
hPDLCs were cultured, genomic DNA was extracted, and genotypes were determined
using the polymerase chain reaction (PCR)-restriction fragment length
polymorphism method. Cells were stimulated with calcitriol with or without VDR
antagonist ZK159222 or osteogenic induction. Alkaline phosphatase, osteocalcin,
and VDR messenger RNA (mRNA) expression were detected using real-time PCR.
Alkaline phosphatase and osteocalcin protein expression were detected by enzyme
activity assays with p-nitrophenyl phosphate substrate and enzyme-linked
immunosorbent assay, respectively. RESULTS: Among the 15 donor cell cultures, the
number of FF, ff, and Ff genotypes were 5, 3, and 7, respectively. There were no
significant differences in expression of alkaline phosphatase or osteocalcin
among the three genotypes in hGFs. However, after stimulation with calcitriol,
alkaline phosphatase and osteocalcin mRNA levels in FF-hPDLCs were significantly
higher than in other hPDLCs genotypes, as was osteocalcin protein expression.
Furthermore, when ZK159222 was included, this difference disappeared, and when
osteogenic induction was performed, alkaline phosphatase and osteocalcin mRNA and
protein levels were higher in FF-hPDLCs than in the other hPDLCs genotypes.
CONCLUSION: The FF-VDR genotype is associated with the most remarkable
upregulation of alkaline phosphatase and osteocalcin in hPDLCs.
PMID- 28492362
TI - Microbiota Analysis of Biofilms on Experimental Abutments Mimicking Dental
Implants: An In Vivo Model.
AB - BACKGROUND: The microbiota colonizing dental implants has been said to be similar
to the microbiome surrounding teeth. In the absence of inflammation, a biofilm
with pathologic bacteria can cover implant surfaces exposed to the oral cavity,
for example, due to a remodeling process. The aim of the present study is to
identify microbiota surrounding exposed dental implants in patients with and
without a history of periodontitis through a deep-sequencing approach. METHODS:
An experimental abutment with the same surface and structure as a commercially
available dental implant was used. Bacterial DNA was isolated, and the 16S
ribosomal RNA gene was amplified and sequenced. Multiplexed tag-encoded
sequencing of DNA from the samples was performed, and the reads were processed by
metagenomic rapid annotation. RESULTS: A wide variety of bacteria, 96 species,
were identified. The most frequently found bacteria were Fusobacterium nucleatum
and Prevotella denticola. Some species generally associated with periodontitis
were found to a greater extent in patients without a history of periodontitis.
Some bacteria that have never been described as part of the oral microbiome were
identified in the present sample. CONCLUSIONS: Analysis of data suggests that the
bacteria surrounding exposed dental implants form a diverse microbiome regardless
of the periodontal profile of patients. Further research is needed to clarify the
role of these microorganisms in the oral environment.
PMID- 28492363
TI - Vagus nerve stimulation improves working memory performance.
AB - Vagus nerve stimulation (VNS) is used for treating refractory epilepsy and major
depression. While the impact of this treatment on seizures has been established,
its impact on human cognition remains equivocal. The goal of this study is to
elucidate the immediate effects of vagus nerve stimulation on attention,
cognition, and emotional reactivity in patients with epilepsy. Twenty patients
(12 male and 8 female; 45 +/- 13 years old) treated with VNS due to refractory
epilepsy participated in the study. Subjects performed a computer-based test of
executive functions embedded with emotional distractors while their brain
activity was recorded with electroencephalography. Subjects' cognitive
performance, early visual event-related potential N1, and frontal alpha asymmetry
were studied when cyclic vagus nerve stimulation was on and when it was off. We
found that vagus nerve stimulation improved working memory performance as seen in
reduced errors on a subtask that relied on working memory, odds ratio (OR) = 0.63
(95% confidence interval, CI [0.47, 0.85]) and increased N1 amplitude, F(1, 15) =
10.17, p = .006. In addition, vagus nerve stimulation resulted in longer reaction
time, F(1, 16) = 8.23, p = .019, and greater frontal alpha asymmetry, F(1, 16) =
11.79, p = .003, in response to threat-related distractors. This is the first
study to show immediate improvement in working memory performance in humans with
clinically relevant vagus nerve stimulation. Furthermore, vagus nerve stimulation
had immediate effects on emotional reactivity evidenced in behavior and brain
physiology.
PMID- 28492364
TI - Na+ influx via Orai1 inhibits intracellular ATP-induced mTORC2 signaling to
disrupt CD4 T cell gene expression and differentiation.
AB - T cell effector functions require sustained calcium influx. However, the
signaling and phenotypic consequences of non-specific sodium permeation via
calcium channels remain unknown. alpha-SNAP is a crucial component of Orai1
channels, and its depletion disrupts the functional assembly of Orai1 multimers.
Here we show that alpha-SNAP hypomorph, hydrocephalus with hopping gait,
Napahyh/hyh mice harbor significant defects in CD4 T cell gene expression and
Foxp3 regulatory T cell (Treg) differentiation. Mechanistically, TCR stimulation
induced rapid sodium influx in Napahyh/hyh CD4 T cells, which reduced
intracellular ATP, [ATP]i. Depletion of [ATP]i inhibited mTORC2 dependent
NFkappaB activation in Napahyh/hyh cells but ablation of Orai1 restored it.
Remarkably, TCR stimulation in the presence of monensin phenocopied the defects
in Napahyh/hyh signaling and Treg differentiation, but not IL-2 expression. Thus,
non-specific sodium influx via bonafide calcium channels disrupts unexpected
signaling nodes and may provide mechanistic insights into some divergent
phenotypes associated with Orai1 function.
PMID- 28492365
TI - The Hippo pathway effector YAP is an essential regulator of ductal progenitor
patterning in the mouse submandibular gland.
AB - Salivary glands, such as submandibular glands (SMGs), are composed of branched
epithelial ductal networks that terminate in acini that together produce,
transport and secrete saliva. Here, we show that the transcriptional regulator
Yap, a key effector of the Hippo pathway, is required for the proper patterning
and morphogenesis of SMG epithelium. Epithelial deletion of Yap in developing
SMGs results in the loss of ductal structures, arising from reduced expression of
the EGF family member Epiregulin, which we show is required for the expansion of
Krt5/Krt14-positive ductal progenitors. We further show that epithelial deletion
of the Lats1 and Lats2 genes, which encode kinases that restrict nuclear Yap
localization, results in morphogenesis defects accompanied by an expansion of
Krt5/Krt14-positive cells. Collectively, our data indicate that Yap-induced
Epiregulin signaling promotes the identity of SMG ductal progenitors and that
removal of nuclear Yap by Lats1/2-mediated signaling is critical for proper
ductal maturation.
PMID- 28492367
TI - Correction: Functional double dissociation within the entorhinal cortex for
visual scene-dependent choice behavior.
PMID- 28492369
TI - C-Reactive Protein Levels Together with the Ranson Scoring System to
Differentiate the Mild and Severe Forms of Acute Pancreatitis.
PMID- 28492366
TI - Digitizing mass spectrometry data to explore the chemical diversity and
distribution of marine cyanobacteria and algae.
AB - Natural product screening programs have uncovered molecules from diverse natural
sources with various biological activities and unique structures. However, much
is yet underexplored and additional information is hidden in these exceptional
collections. We applied untargeted mass spectrometry approaches to capture the
chemical space and dispersal patterns of metabolites from an in-house library of
marine cyanobacterial and algal collections. Remarkably, 86% of the metabolomics
signals detected were not found in other available datasets of similar nature,
supporting the hypothesis that marine cyanobacteria and algae possess distinctive
metabolomes. The data were plotted onto a world map representing eight major
sampling sites, and revealed potential geographic locations with high chemical
diversity. We demonstrate the use of these inventories as a tool to explore the
diversity and distribution of natural products. Finally, we utilized this tool to
guide the isolation of a new cyclic lipopeptide, yuvalamide A, from a marine
cyanobacterium.
PMID- 28492370
TI - Non-invasive diagnosis of esophageal varices after Baveno VI.
AB - A major complication of portal hypertension in patients with cirrhosis is the
development of esophageal varices with the associated risk of variceal bleeding.
Hence, the Baveno consensus on portal hypertension in its first five editions had
recommended surveillance with periodic upper endoscopies in these patients to
identify in a timely fashion the development of esophageal varices and initiate a
primary prophylaxis strategy in those at a high risk of bleeding. For the first
time, the Sixth Baveno Consensus on Portal Hypertension (Baveno VI) recommended
using non-invasive tools to rule out the presence of varices with a high risk of
bleeding. According to Baveno VI, surveillance endoscopy is not necessary for
patients with "compensated advanced chronic liver disease" (cACLD) who have
normal platelets (>150*109/L) and a liver stiffness measure (LSM) <20 kPa. In
this review, we will briefly describe the currently available non-invasive
methods to predict the presence of varices, such as serum tests, imaging, and
elastography. We will also discuss the rationale that led to Baveno VI
recommendation and describe the studies that have validated Baveno VI criteria
after its publication. Finally, we will mention some potential caveats and
suggest some areas for future research.
PMID- 28492371
TI - Prognostic value of tumoral expression of galectin-9 in gastric cancer.
AB - BACKGROUND/AIMS: Galectin-9 (Gal-9) is a member of the beta-galactoside-binding
lectin family. Our previous study revealed that Gal-9 suppresses migration,
invasion, and epithelial-mesenchymal transition in gastric cancer cells. Gal-9
was reported to have anti-metastatic activity in patients with malignant
melanoma, breast cancer, and hepatocellular carcinoma. Therefore, we aimed to
evaluate the prognostic significance of Gal-9 in patients with gastric cancer.
MATERIALS AND METHODS: The clinical significance of Gal-9 was explored using
clinical and pathological data from 619 patients with gastric cancer who
underwent gastrectomy at National Cancer Center, Korea. Tissue microarray and
immunohistochemical analyses were used to evaluate Gal-9 expression. The median
follow-up duration was 65.7 months (range 0-79 months). Kaplan-Meier method was
used to evaluate survival. Log-rank test was used to assess the differences in
survival. RESULTS: Based on the tumoral expression of Gal-9, 619 patients with
gastric cancer were classified into two groups: Gal-9-positive patients (327,
52.8%) and Gal-9-negative patients (292, 47.2%). The Gal-9-positive group had a
significantly lower overall (p=0.001, by log-rank test) and gastric cancer
specific mortalities (p<0.001) compared to the Gal-9-negative group. In
multivariate analysis, which included the depth of invasion and lymph-node
metastasis, Gal-9 positivity showed a trend toward improved prognosis but did not
reach statistical significance (hazard ratio, 0.8; 95% confidence interval, 0.55
1.31). CONCLUSION: Tumoral expression of Gal-9 may suppress tumor progression in
patients with gastric cancer.
PMID- 28492372
TI - Re: HLA is better than serological screening for celiac diseases in
rheumatological arthritis.
PMID- 28492373
TI - Re: How to predict the severity of acute pancreatitis? An ongoing debate.
PMID- 28492374
TI - A miniaturized wall-climbing segment robot inspired by caterpillar locomotion.
AB - Caterpillars are very successful soft-bodied climbers that navigate in complex
environments. This paper develops a multi-segmented robot climbing on vertical
surfaces using dry adhesive pads, inspired by caterpillar locomotion. The
miniaturized robot consists of four segments, and each segment uses a solenoid
actuator with a permanent magnet plunger. The head and body segments adapt a
novel mechanism and Scott-Russell linkages to generate a bi-directional plane
motion using one solenoid actuator, resulting to reliable attaching and peeling
motions of gecko pads. A tail is also attached at the back of the last segment to
avoid falling or exhibiting unstable motion. Gecko-inspired adhesive pads are
fabricated from polydimethylsiloxane (PDMS) with the area of 20 mm * 10 mm. We
have conducted experiments on the locomotion performance of the segment robot
climbing vertical surfaces for two types of locomotion, achieving the fast and
stable climbing motion.
PMID- 28492375
TI - Combat Experience and Mental Health in the Israel National Health Survey.
AB - OBJECTIVE: To compare the mental health status of those who participated in
combat related activities during their service with that of soldiers whose army
service did not include combat related activities Method: A representative sample
extracted from the National Population Register of non-institutionalized
residents aged 21 or older of Israel was used in this crosssectional survey. Data
on mental health disorders, sociodemographic background and army service were
collected using face-to-face computer-assisted interviews. RESULTS: Combat
experience per se was not associated with lifetime diagnosis of PTSD. Former
combat soldiers had significantly lower lifetime prevalence and 12 months
prevalence of any mood or anxiety disorders including PTSD. CONCLUSION: This work
is in line with previous literature showing that combat exposure, as such, has
limited contribution to lifetime PTSD in some groups of veterans. The inverse
relationship between combat exposure and PTSD might be explained by the selection
of potential combatants among all recruits and by the heightened preparedness to
military life stressors.
PMID- 28492376
TI - Cannabis and Alcohol Abuse Among First Psychotic Episode Inpatients.
AB - BACKGROUND: Psychoactive substance abuse, which includes abuse of alcohol and
street drugs, is common among first-episode psychosis patients, but the
prevalence of cannabis abuse is particularly high. However, there have been very
few reported studies concerning the occurrence of psychoactive substance abuse
among first-episode psychotic individuals using standard toxicological testing.
We study the prevalence of cannabis and alcohol abuse among first
psychoticepisode inpatients as well as compare the demographic, diagnostic, and
psychopathological profiles of substance abusers versus nonusers. METHODS:
Subjects were recruited from the Jerusalem Mental Health Center between 2012 and
2014. Ninety-one consecutively admitted psychiatric patients diagnosed using the
DSM-IV criteria with a first psychotic episode due to schizophrenia,
schizophreniform disorder, bipolar disorder, brief psychotic episode, and
psychosis NOS disorder entered the study. The diagnoses of schizophrenia (all
types), psychosis NOS disorder, brief psychotic episode, and schizophreniform
disorder were categorized as "only psychosis" and those of bipolar disorder manic
episode with psychotic features (congruent and incongruent) and severe depression
with psychotic features were categorized as "predominantly affective symptoms."
Urine tests for tetrahydrocannabinol (THC) were performed during the first 48
hours of admission, and likewise self-report questionnaires were administered.
Alcohol abuse and dependence were diagnosed by self-report. RESULTS: Of the 91
subjects in the study, 49 (53.8%) did not abuse any illegal psychoactive
substance. Twenty patients (22%) abused only cannabis; 14 (15.4%) abused cannabis
and another psychoactive substance; 54 (59.3%) of the subjects reported no
alcohol abuse; 33 (36.3%) reported occasional drinking (between two and ten times
a month); and 4 (4.4%) reported continuous repeated drinking (more than ten times
a month). There was no correlation between the demographic characteristics and
the abuse of cannabis. Two-thirds of the "predominantly affective symptoms"
subjects were positive for THC, whereas only a third of the "only psychosis"
subjects screened positive for THC. CONCLUSIONS: The percentage of cannabis and
alcohol abuse in the study population is much higher than one would expect to see
in the general Israeli population (according to the Knesset Research Department
7.6-10.2% of the adult Israeli population abuse cannabis). Different patterns of
cannabis abuse among "predominantly affective" and "psychotic only" patients may
lend credence to the preferential use of a specific substance per diagnosis.
PMID- 28492377
TI - The Association between Obesity and Symptoms of Psychopathology and its
Relationship with Sedentary Behavior and Mediterranean Diet.
AB - BACKGROUND: Recent research indicates an association between obesity and symptoms
of psychopathology, the nature of which remains obscure. This study examined the
confounding role of behavioral factors on this association. METHOD: One hundred
and forty-two overweight/obese subjects who sought treatment for obesity, of both
genders (51 males and 91 females), 18 to 64 years old and 139 normal-weight
controls of both genders (41 males and 98 females), 18 to 63 years old, were
enrolled in this study. We measured psychopathology features, using the Symptom
Checklist 90-Revised (SCL-90-R), dietary habits, using the MedDietScore (MDS)
questionnaire, and physical activity, using the International Physical Activity
Questionnaire (IPAQ). A series of regression models were used to estimate the
mediation of dietary patterns and physical activity on the obesity
psychopathology association. RESULTS: The associations between obesity and
depression (beta=0.32/beta=0.15), obsession-compulsion (beta=0.03/beta=-0.13),
anxiety (beta=-0.25/beta=-0.12), interpersonal sensitivity (beta=0.08/beta=-0.04)
and psychoticism (beta=-0.01/ beta=0.025) are accounted for by sedentary behavior
and Mediterranean diet. CONCLUSIONS: Our data suggest that modifiable behavioral
factors such as sedentary time and dietary patterns positively affect the
association between obesity and symptoms of psychopathology.
PMID- 28492378
TI - Short-term Focused Inpatient Treatment Combined with Sensory Regulation of Sexual
Trauma Victims - Summary of 100 First Hospitalizations.
AB - BACKGROUND: Treatment of sexual trauma victims may be fraught with crises. In
situations of de-compensation, the frequency of suicide attempts is high, and
ambulatory treatment may not always provide the required response. In extreme
cases, either in close proximity to the sexual offence or even years later, a
more intense intervention is needed. This includes removing sexual trauma victims
from their daily lives and hospitalization. Caregivers debate the type of
hospitalization needed and the best type of treatment in times of decompensation
and dissociation. METHOD: This paper depicts a hospitalization model in Israel
that has been created to provide a unique and focused solution for sexual trauma
victims. The psychological principle of the hospitalization is based on Mann's
shortterm dynamic psychotherapy method. The patients are integrated in an acute
psychiatric ward in which a variety of psychopathologies, men and women, are
treated. RESULTS: The paper summarizes findings and understandings from the first
100 hospitalizations. The author's main conclusion is that sexual trauma victims
need a focused specialized treatment plan to best deal with their complex issues
and that hospitalization should be minimized to two weeks. CONCLUSIONS: The
author's main recommendation is that funding must be allocated for hospital beds
for sexual trauma victims in each region in the country to produce adequate
continuity of care for these patients.
PMID- 28492379
TI - Psychological Factors Associated with Emotional Distress among Palestinian Arabs
from East Jerusalem Accessing Psychiatric Care in Israel.
AB - BACKGROUND: The Palestinian population residing in East Jerusalem is
characterized by high rates of poverty and unemployment and is subject to
discrimination in various forms, including infrastructure of mental health
services. Little is known about the help seeking needs and practices of East
Jerusalem residents. METHOD: We examined socio-demographic and clinical
characteristics of a consecutive sample Palestinian residents from East Jerusalem
(N=50) who accessed a specially assigned psychiatric clinic in Israel. In
addition, we examined the psychological factors associated with emotional
distress among these service-users upon entry to care. Participants completed a
survey in Arabic that included a socio-demographic questionnaire and measures
assessing emotional distress, perceived exposure to discrimination and social
support, and mental health stigma. RESULTS: Participants reported high levels of
emotional distress. Female gender, low socioeconomic status, higher perceived
exposure to discrimination and higher perceived social support were associated
with increased emotional distress. CONCLUSIONS: Findings add to the scarce body
of knowledge on specific mental health characteristics of East Jerusalem
Palestinian residents.
PMID- 28492380
TI - Religious-Ethnic Differences in Prevalence and Correlates of Suicidal Ideation
and Attempts Among Israeli Vocational Education Students.
AB - BACKGROUND: The current study is the first to examine serious suicidal ideation,
suicide attempts and psychological distress among students belonging to different
religious-ethnic groups attending VET high schools. METHOD: 3,553 students
studying in the VET high schools completed a self-report survey. The survey
evaluated serious suicidal ideation, suicide attempts, depression, anxiety,
somatization, self-efficacy, belonging and sociodemographic variables. RESULTS:
Students coming from minority groups (Arab Muslim, Bedouin Arab Muslim, Druze)
are more likely to have seriously considered suicide or attempted suicide
compared to their Jewish counterparts, with the exception of Christian Arabs.
Bedouin Arab Muslim students were more susceptible to suicide ideation and
attempts upon high depression levels. CONCLUSIONS: Minority youth at VET schools
are at greater risk of experiencing suicidal ideation and attempting suicide
compared to non-minority students. The education system must be highly alert to
depressive symptoms among Bedouin Arab Muslim students since they may pose a
greater risk to develop into suicidal ideation and attempt.
PMID- 28492381
TI - Cultural Impact on SAD: Social Anxiety Disorder among Ethiopian and Former Soviet
Union Immigrants to Israel, in Comparison to Native-born Israelis.
AB - BACKGROUND: Social Anxiety Disorder (SAD) is linked to social norms and role
expectations which are culture dependent, such as the construal of one's self as
independent or interdependent in relation to others. The current study is the
first to examine SAD symptoms among Ethiopian and former Soviet Union immigrants
to Israel compared to a sample of native Israelis. We investigated the
relationship between SAD, ethnicity and independent/ interdependent self
construals. METHODS: A total of 261 students (151 native-born Israelis, 60
Ethiopian immigrants and 50 students from the former USSR) were administrated the
Liebowitz Scale (LSAS), the Self-construal Scale (SCS), Beck Depression Inventory
(BDI) and a socio-demographic questionnaire. RESULTS: Ethiopians exhibited
highest SAD scores while no differences were found between the FSU immigrants and
native-born Israelis. Additionally, Ethiopians and native-born Israeli students
exhibited similar high interdependence scores. Finally, SAD scores were predicted
by gender, origin, independent and interdependent self-construals. CONCLUSION:
Immigration per se is not a universal risk factor of SAD and ethnological
cultural factors do contribute specifically to SAD. A possible psychological
mediator between culture and the susceptibility to SAD are the interdependence
and independent self-construals. When treating immigrants, clinicians and health
care providers are advised to consider the effect of cultural influence on the
mental well-being and integration process of immigrants in to their host country.
PMID- 28492382
TI - Assessing the Use of the Child Attachment Interview in a Sample of Israeli Jewish
Children.
AB - BACKGROUND: This manuscript assesses the use of the Child Attachment Interview
(CAI) in a sample of Israeli Jewish children in middle childhood in order to add
to empirical data on this measure. METHOD: Forty-one children between the ages of
7 and 13 were consecutively recruited to the study. The clinical sample included
29 children diagnosed with anxiety disorder, major depression or ADHD. The Father
Focused Referral (FFR) sample included 12 children whose father was unavailable
to them. Participants were administered the CAI and coded by certified personnel.
RESULTS: 81.4% concordance was found between maternal and paternal secure
insecure attachment classifications in the clinical sample; 100% of the children
in the FFR group were classified as insecurely attached to their fathers
suggesting convergent validity for the classification of father attachment; 45.4%
of the children in the FFR sample were also classified as insecurely attached to
their mothers, pointing to the difference that can be found between the two
parental attachment classifications in relevant cases, and therefore to
sufficient discriminant validity between the two classifications. CONCLUSIONS:
The clinical sample concordance rate, which was lower than in previous studies,
indicates that parental concordance rates should be further investigated using
different samples and countries. The study's findings regarding the difference
that can be found between parental attachment classifications show the
instrument's relevance in cases which the parental representations may differ. In
these cases, using an instrument that does not examine the attachment toward both
parents might not suffice. Study limitations and further implications are
discussed.
PMID- 28492383
TI - Parent-child Interaction Treatment for Preschoolers with Feeding Disorders.
AB - BACKGROUND: This study examined the immediate outcome of Feeding Disorders (FD)
in preschoolers referred to the family treatment program Cerco Asilo. METHOD: 21
children (mean age [SD=1]: 39 months [1]; range 9-65 months) with a diagnosis of
FD were included in the treatment for 24 weeks. Specifically, seven subjects were
diagnosed with Infantile Anorexia (IA), nine subjects with Sensory Food Aversion
(SFA), and five subjects with Feeding Disorder of Caregiver-Infant Reciprocity
(FDCIR). RESULTS: The great majority of patients with SFA and with FDCIR resolved
the FD, whereas children with IA did not respond well to the treatment.
LIMITATIONS: The study's main limitations are the relatively small sample size,
and the lack of a control group. CONCLUSIONS: Findings suggest that changes in
the parentchild relationship could generally promote FD resolution, other than
IA. These data may have implications for clinical practice suggesting the need to
develop ad hoc intervention protocols tailored to children with IA and their
families.
PMID- 28492384
TI - Effect of Dexmedetomidine and Propofol on Basal Ganglia Activity in Parkinson
Disease: A Controlled Clinical Trial.
AB - BACKGROUND: Deep brain stimulation electrodes can record oscillatory activity
from deep brain structures, known as local field potentials. The authors'
objective was to evaluate and quantify the effects of dexmedetomidine (0.2
MUg.kg.h) on local field potentials in patients with Parkinson disease undergoing
deep brain stimulation surgery compared with control recording (primary outcome),
as well as the effect of propofol at different estimated peak effect site
concentrations (0.5, 1.0, 1.5, 2.0, and 2.5 MUg/ml) from control recording.
METHODS: A nonrandomized, nonblinded controlled clinical trial was carried out to
assess the change in local field potentials activity over time in 10 patients
with Parkinson disease who underwent deep brain stimulation placement surgery (18
subthalamic nuclei). The relationship was assessed between the activity in nuclei
in the same patient at a given time and repeated measures from the same nucleus
over time. RESULTS: No significant difference was observed between the relative
beta power of local field potentials in dexmedetomidine and control recordings (
7.7; 95% CI, -18.9 to 7.6). By contrast, there was a significant decline of 12.7%
(95% CI, -21.3 to -4.7) in the relative beta power of the local field potentials
for each increment in the estimated peak propofol concentrations at the effect
site relative to the control recordings. CONCLUSIONS: Dexmedetomidine (0.2
MUg.kg.h) did not show effect on local field potentials compared with control
recording. A significant deep brain activity decline from control recording was
observed with incremental doses of propofol.
PMID- 28492386
TI - From the Editor.
PMID- 28492385
TI - The Prognostic Value of Central Venous-to-Arterial CO2 Difference/Arterial
Central Venous O2 Difference Ratio in Septic Shock Patients with Central Venous
O2 Saturation >=80.
AB - BACKGROUND: It is a great challenge for physician to assess the relationship
between O2 delivery and O2 consumption in septic shock patients with high ScvO2.
Recently, the venous-to-arterial CO2 difference/arterial-central venous O2
difference ratio (P(v-a)CO2/C(a-v)O2) has shown potential for reflecting
anaerobic metabolism. Therefore, we evaluated the value of using the P(v
a)CO2/C(a-v)O2 ratio to predict mortality and assess anaerobic metabolism in
septic shock patients with high ScvO2 (>= 80%). METHODS: This was a clinical
investigation of septic shock patients on the P(v-a)CO2/C(a-v)O2 ratio in the
intensive care unit (ICU) department. The patients' arterial and central venous
blood gas levels were measured simultaneously at enrollment (T0) and 24 h (T24)
after resuscitation. RESULTS: A total of 61 patients with high ScvO2 at T24 after
resuscitation were selected for analysis. The ICU mortality rate in the septic
shock patients was 20% (12/61). The nonsurvivors had a significantly higher P(v
a)CO2, P(v-a)CO2/C(a-v) O2 ratio, arterial lactate level and lower lactate
clearance at T24 after resuscitation. The P(v-a)CO2/C(a-v)O2 ratio had the
biggest the areas under the receiver operating characteristic (AUC) for
predicting ICU mortality. For predicting ICU mortality, a threshold of P(v
a)CO2/C(a-v)O2 ratio >=1.6 was associated with a sensitivity of 83% and a
specificity of 63%. Multivariate analysis showed P(v-a)CO2/C(a-v)O2 ratio at both
T0 (RR 5.597, P = 0.024) and T24 (RR 5.812, P = 0.031) was an independent
predictor of ICU mortality. Including the ratio into the regression model showed
a bigger AUC than without the ratio (0.886 vs. 0.833). CONCLUSIONS: The P(v
a)CO2/C(a-v)O2 ratio is an independent predictor of ICU mortality in septic shock
patients with high ScvO2 after resuscitation. It is worthy of consideration to
recruit microcirculation to correct the high ratio in high ScvO2 case.
PMID- 28492387
TI - Letter to the Editor.
PMID- 28492388
TI - Letter to the Editor.
PMID- 28492389
TI - "What About the Next Generation That's Coming?": The Recontextualization of
Mothering Post-Refugee Resettlement.
AB - The purpose of this analysis was to explore the recontextualization of mothering
in Karen refugees from Burma. We collected ethnographic data over an 11-month
period with a cohort of 12 Karen women postresettlement. Using Spradley's and
tools of critical discourse analysis, we interpreted the migration narratives of
women, in particular, experiences they shared as mothers. These narratives were
grounded in the space of cultural difference; thus, we engaged hybridity as a
theoretical frame. Findings reflect the negotiation of mothering practices within
the norms, structures, and policies of the country of resettlement. We identified
the spaces of transformation a woman constructed to usher change while sustaining
a connection between herself, her culture, and her children.
PMID- 28492390
TI - Challenges in tuberculosis/HIV management in a country with a concentrated HIV
epidemic.
PMID- 28492391
TI - Hepatitis C virus drives increased type I interferon-associated impairments
associated with fibrosis severity in antiretroviral treatment-treated HIV-1
hepatitis C virus-coinfected individuals.
AB - BACKGROUND: Viral coinfections might contribute to the increased immune
activation and inflammation that persist in antiretroviral treatment (ART)
treated HIV-1 patients. We investigated whether the hepatitis C virus (HCV)
coinfection contributes to such alterations by impairing the plasmacytoid
dendritic cell (pDC) IFNalpha/TLR7 pathway in a highly homogeneous group of ART
treated HIV-1-HCV-coinfected patients. METHODS: Twenty-nine HIV-1-infected
patients with fully suppressive ART were included, 15 of whom being HCV
coinfected with mild-to-moderate fibrosis and matched for their HIV-1 disease,
and 13 control healthy donors. Cellular activation, plasma levels of inflammatory
cytokines and pDC transcriptome associated with IFNalpha/TLR7 pathway were
characterized. RESULTS: Higher plasma levels of type-I interferon (IFN)
associated cytokines [interferon gamma-induced protein 10 (IP-10), MIP-1beta, IL
8 and IFN-inducible T-cell alpha chemoattractant) were observed in HIV-1-HCV
coinfected than in HIV-1-monoinfected patients (P = 0.0007, 0.028, 0.028 and
0.035, respectively). The pDCs and T cells displayed a more exhausted (LAG-3+ and
CD57+, respectively) phenotype. The pDC IFNalpha pathway (defined by
phosphorylated STAT1 expression) was constitutively activated in all patients,
irrespective of HCV coinfection. Expression of interferon-stimulated genes (ISGs)
EI2AK2, ISG15, Mx1 and IFI44 was increased in pDCs from HIV-1-HCV-coinfected
individuals and was correlated with fibrosis score (Fibroscan, www.echosens.com,
Paris, France and aspartate-aminotransferase/platelet-ratio index score, P =
0.026 and 0.019, respectively). Plasma levels of IP-10, STAT1 expression in pDCs
and Mx1 mRNA levels in pDCs decreased after interferon-free anti-HCV treatment.
CONCLUSION: HCV replication appears to drive increases in type-I IFN-associated
inflammation and ISGs expression in pDCs, in association with fibrosis severity
in ART-treated HIV-1-infected patients with mild-to-moderate fibrosis.
Preliminary results indicate reduction of these alterations with earlier
interferon-free anti-HCV treatment in those patients.
PMID- 28492392
TI - Predictors of estimated glomerular filtration rate progression, stabilization or
improvement after chronic renal impairment in HIV-positive individuals.
AB - OBJECTIVES: The objectives of this analysis were to investigate predictors of
progression, stabilization or improvement in estimated glomerular filtration rate
(eGFR) after development of chronic renal impairment (CRI) in HIV-positive
individuals. DESIGN: Prospective observational study. METHODS: The Data
Collection on Adverse events of Anti-HIV Drugs (D:A:D) study participants
progressing to CRI defined as confirmed, at least 3 months apart, and eGFR 70
ml/min per 1.73 m or less were included in the analysis. The median of all eGFRs
measured 24-36 months post-CRI was compared with the median eGFR defining CRI,
and changes were grouped into improvement (>+10 ml/min per 1.73 m), stabilization
(-10 to +10 ml/min per 1.73 m) and progression (<-10 ml/min per 1.73 m). Adjusted
polynomial regression models assessed odds of better eGFR outcomes after CRI,
assuming that eGFR improvement is better than stabilization which in turn is
better than progression. RESULTS: Of 2006 individuals developing CRI, 21%
subsequently improved eGFR, 67% stabilized and 12% progressed. Individuals
remaining on tenofovir (TDF) or atazanavir boosted with ritonavir (ATV/r) 24
months post-CRI had worse eGFR outcomes compared with those unexposed [TDF: 0.47
(0.35-0.63) and ATV/r: 0.63 (0.48-0.82)]. Individuals off TDF for 12-24 months
[0.75 (0.50-1.13)] or off ATV/r for more than 12 months [1.17 (0.87-1.57)] had
similar eGFR outcomes as those unexposed to these antiretrovirals. Older age,
hypertension, later date of CRI and diabetes were associated with worse eGFR
outcomes. CONCLUSION: Current TDF and ATV/r use after a diagnosis of CRI was
associated with worse eGFR outcomes. In contrast, TDF and ATV/r discontinuation
lead to similar longer term eGFR outcomes as in those unexposed, suggesting that
these drug-associated eGFR declines may be halted or reversed after their
cessation.
PMID- 28492393
TI - Long-term alcohol use patterns and HIV disease severity.
AB - OBJECTIVE: We examined the relationship between alcohol use trajectories and HIV
disease severity among men and women participating in the Veterans Aging Cohort
Study (VACS). DESIGN: Prospective cohort of HIV-infected persons in care at eight
US Veterans Health Administration sites. METHODS: Between 2002 and 2010, we
assessed alcohol consumption annually using the alcohol use disorders
identification test-consumption (AUDIT-C). HIV disease severity was ascertained
using the VACS index, a validated measure of morbidity and all-cause mortality.
We examined the relationship between alcohol use and HIV disease severity
patterns using joint trajectory modeling. Alcohol use trajectories were validated
using phosphatidylethanol - a biomarker of alcohol consumption - measured between
2005 and 2006 among a subset of participants. We examined associations between
membership in alcohol use and VACS index trajectories using multinomial
regression. RESULTS: Among eligible participants, we identified four alcohol
consumption trajectories: abstainers (24% of the sample), lower risk (44%),
moderate risk (24%), and higher risk drinkers (8%). Alcohol use trajectories were
highly correlated with phosphatidylethanol (Cramer's V = 0.465, P < 0.001): mean
concentrations were 4.4, 17.8, 57.7, and 167.6 ng/ml in the abstainer, lower
risk, moderate risk, and higher risk groups, respectively. Four VACS index
trajectories were identified: low (2%), moderate (46%), high (36%), and extreme
(16%). Higher risk drinkers were most common in the extreme VACS index group, and
were absent in the low index group. In multivariable analysis, the association
between alcohol use and VACS index trajectory membership remained significant (P
= 0.002). CONCLUSION: Alcohol use trajectories characterized by persistent
unhealthy drinking are associated with more advanced HIV disease severity among
HIV-infected veterans in the United States.
PMID- 28492394
TI - Sub-Saharan African migrants have slower initial CD4+ cell recovery after
combined antiretroviral treatment initiation than French natives.
AB - OBJECTIVE: Poorer immunologic responses to combined antiretroviral treatment
(cART) have been reported among sub-Saharan African (SSA) migrants than among
native Europeans. We studied whether differences in CD4 cell recovery between
French natives and SSA migrants starting first-line cART could be explained by
differences in socioeconomic conditions, inflammatory marker levels, and other
established determinants. METHODS: We compared 319 French natives and 175 SSA
migrants (ANRS-COPANA cohort). Clinical, biological, and socioeconomic data
(education, employment, income, and cohabiting partnership) were recorded at
regular visits. A piecewise linear mixed-effects model was used to analyze CD4
cell count kinetics on cART. RESULTS: Compared with French natives, SSA migrants
were more frequently women, younger, less educated, living in more adverse
conditions, and had more frequent symptoms of depression. The rate of CD4 cell
recovery during the first 4 months on cART was significantly slower in SSA
migrants, despite a similar virologic response, but did not differ significantly
thereafter. The mean CD4 cell count rose from 251 cells/MUl at baseline to 508
cells/MUl at 36 months in migrants, and from 308 to 623 cells/MUl in natives
(additional mean gain of 58 cells/MUl in natives). The difference persisted after
adjustment for clinical, updated socioeconomic, and living conditions (-0.40?CD4
cells/month, P = 0.04); 25-hydroxyvitamin D, monocyte chemoattractant protein-1
and soluble tumor necrosis factor receptor 1 (sTNFR1) levels were lower in SSA
migrants, but only sTNFR1 contributed to the difference in CD4 slope. CONCLUSION:
Initial CD4 cell recovery on cART was slower among SSA migrants than among French
natives. This difference was not explained by established clinical and biological
determinants or by socioeconomic status.
PMID- 28492395
TI - HIV prevention: response to pre-exposure prophylaxis failure with tenofovir
disoproxil.
PMID- 28492396
TI - Preexposure prophylaxis failure with tenofovir disoproxil.
PMID- 28492397
TI - Post-treatment control in an adult with perinatally acquired HIV following
cessation of antiretroviral therapy.
PMID- 28492398
TI - Chronic hepatitis E in HIV/HBV coinfected patient: lack of power of sofosbuvir
ribavirin.
PMID- 28492399
TI - Acute Kidney Injury After Pediatric Cardiac Surgery: A Secondary Analysis of the
Safe Pediatric Euglycemia After Cardiac Surgery Trial.
AB - OBJECTIVES: To understand the effect of tight glycemic control on cardiac surgery
associated acute kidney injury. DESIGN: Secondary analysis of data from the Safe
Pediatric Euglycemia after Cardiac Surgery trial of tight glycemic control versus
standard care. SETTING: Pediatric cardiac ICUs at University of Michigan, C.S.
Mott Children's Hospital, and Boston Children's Hospital. PATIENTS: Children 0-36
months old undergoing congenital cardiac surgery. INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: Cardiac surgery-associated acute kidney injury was
assigned using the Acute Kidney Injury Network criteria with the modification
that a greater than 0.1 mg/dL increase in serum creatinine was required to assign
cardiac surgery-associated acute kidney injury. We explored associations between
cardiac surgery-associated acute kidney injury and tight glycemic control and
clinical outcomes. Of 799 patients studied, cardiac surgery-associated acute
kidney injury occurred in 289 patients (36%), most of whom had stage II or III
disease (72%). Cardiac surgery-associated acute kidney injury rates were similar
between treatment groups (36% vs 36%; p = 0.99). Multivariable modeling showed
that patients with cardiac surgery-associated acute kidney injury were younger (p
= 0.002), underwent more complex surgery (p = 0.005), and had longer
cardiopulmonary bypass times (p = 0.002). Cardiac surgery-associated acute kidney
injury was associated with longer mechanical ventilation and ICU and hospital
stays and increased mortality. Patients at University of Michigan had higher
rates of cardiac surgery-associated acute kidney injury compared with Boston
Children's Hospital patients (66% vs 15%; p < 0.001), but University of Michigan
patients with cardiac surgery-associated acute kidney injury had shorter time to
extubation and ICU and hospital stays compared with Boston Children's Hospital
patients. CONCLUSIONS: Tight glycemic control did not reduce the cardiac surgery
associated acute kidney injury rate in this trial cohort. We observed significant
differences in cardiac surgery-associated acute kidney injury rates between the
two study sites, and there was a differential effect of cardiac surgery
associated acute kidney injury on clinical outcomes by site. These findings
warrant further investigation to identify causal variation in perioperative
practices that affect cardiac surgery-associated acute kidney injury
epidemiology.
PMID- 28492400
TI - Epinephrine Auto-Injector Versus Drawn Up Epinephrine for Anaphylaxis Management:
A Scoping Review.
AB - OBJECTIVE: Anaphylaxis is a life-threatening event. Most clinical symptoms of
anaphylaxis can be reversed by prompt intramuscular administration of epinephrine
using an auto-injector or epinephrine drawn up in a syringe and delays and errors
may be fatal. The aim of this scoping review is to identify and compare errors
associated with use of epinephrine drawn up in a syringe versus epinephrine auto
injectors in order to assist hospitals as they choose which approach minimizes
risk of adverse events for their patients. DATA SOURCES: PubMed, Embase, CINAHL,
Web of Science, and the Cochrane Library were searched using terms agreed to a
priori. STUDY SELECTION: We reviewed human and simulation studies reporting
errors associated with the use of epinephrine in anaphylaxis. There were multiple
screening stages with evolving feedback. DATA EXTRACTION: Each study was
independently assessed by two reviewers for eligibility. Data were extracted
using an instrument modeled from the Zaza et al instrument and grouped into
themes. DATA SYNTHESIS: Three main themes were noted: 1) ergonomics, 2) dosing
errors, and 3) errors due to route of administration. Significant knowledge gaps
in the operation of epinephrine auto-injectors among healthcare providers,
patients, and caregivers were identified. For epinephrine in a syringe, there
were more frequent reports of incorrect dosing and erroneous IV administration
with associated adverse cardiac events. For the epinephrine auto-injector,
unintentional administration to the digit was an error reported on multiple
occasions. CONCLUSIONS: This scoping review highlights knowledge gaps and a
diverse set of errors regardless of the approach to epinephrine preparation
during management of anaphylaxis. There are more potentially life-threatening
errors reported for epinephrine drawn up in a syringe than with the auto
injectors. The impact of these knowledge gaps and potentially fatal errors on
patient outcomes, cost, and quality of care is worthy of further investigation.
PMID- 28492401
TI - Renal Function Follow-Up and Renal Recovery After Acute Kidney Injury in
Critically Ill Children.
AB - OBJECTIVES: To evaluate factors associated with renal recovery from acute kidney
injury in critically ill children and the extent to which serum creatinine is
measured before discharge. DESIGN: Retrospective cohort study. SETTING: Two PICUs
at tertiary centers in Montreal, QC, Canada. PATIENTS: Children (< 18 yr old)
admitted to the PICU between 2003 and 2005. Patients with end-stage renal
disease, no healthcare number, died during admission, or admitted postcardiac
surgery were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Acute
kidney injury was defined using internationally accepted criteria (Kidney
Disease: Improving Global Outcomes). Two renal recovery outcomes commonly used in
the literature were evaluated: hospital discharge serum creatinine less than 1.5
and less than 1.15 times baseline. Proportions of patients with 1) serum
creatinine measurements between PICU and hospital discharge and 2) renal recovery
were calculated. Univariate and multivariate analyses were performed to determine
factors associated with serum creatinine monitoring and nonrecovery after acute
kidney injury. Of 2,033 patients included, 829 (40.8%) had serum creatinine
measurements between PICU and hospital discharge. The odds of having a discharge
serum creatinine measurement increased with acute kidney injury severity (stages
1, 2, 3 adjusted odds ratio [95% CI]: 1.49 [1.03-2.15], 2.52 [1.40-4.54], 7.87
[3.16-19.60], respectively). Acute kidney injury recovery was 92.5% when defined
as serum creatinine less than 1.5 times baseline versus 75.9% when defined as
less than 1.15 times baseline (p < 0.001). Stage 3 acute kidney injury was
associated with having a discharge serum creatinine greater than or equal to 1.5
times baseline (adjusted odds ratio = 3.51 [1.33-9.19]). CONCLUSIONS: Less than
half the PICU population had serum creatinine measured before hospital discharge.
More severe acute kidney injury was associated with higher likelihood of serum
creatinine monitoring and lower probability of acute kidney injury recovery.
Future research should address knowledge translation on post-PICU acute kidney
injury follow-up before hospital discharge.
PMID- 28492402
TI - Can the Pediatric Logistic Organ Dysfunction-2 Score on Day 1 Be Used in Clinical
Criteria for Sepsis in Children?
AB - OBJECTIVE: A recent task force has proposed the use of Sequential Organ Failure
Assessment in clinical criteria for sepsis in adults. We sought to evaluate the
predictive validity for PICU mortality of the Pediatric Logistic Organ
Dysfunction-2 and of the "quick" Pediatric Logistic Organ Dysfunction-2 scores on
day 1 in children with suspected infection. DESIGN: Secondary analysis of the
database used for the development and validation of the Pediatric Logistic Organ
Dysfunction-2. SETTINGS: Nine university-affiliated PICUs in Europe. PATIENTS:
Only children with hypotension-low systolic blood pressure or low mean blood
pressure using age-adapted cutoffs-and lactatemia greater than 2 mmol/L were
considered in shock. MEASUREMENTS AND MAIN RESULTS: We developed the quick
Pediatric Logistic Organ Dysfunction-2 score on day 1 including tachycardia,
hypotension, and altered mentation (Glasgow < 11): one point for each variable
(range, 0-3). Outcome was mortality at PICU discharge. Discrimination (Area under
receiver operating characteristic curve-95% CI) and calibration (goodness of fit
test) of the scores were studied. This study included 862 children with suspected
infection (median age: 12.3 mo; mortality: n = 60 [7.0%]). Area under the curve
of the Pediatric Logistic Organ Dysfunction-2 score on day 1 was 0.91 (0.86-0.96)
in children with suspected infection, 0.88 (0.79-0.96) in those with low systolic
blood pressure and hyperlactatemia, and 0.91 (0.85-0.97) in those with low mean
blood pressure and hyperlactatemia; calibration p value was 0.03, 0.36, and 0.49,
respectively. A Pediatric Logistic Organ Dysfunction-2 score on day 1 greater
than or equal to 8 reflected an overall risk of mortality greater than or equal
to 9.3% in children with suspected infection. Area under the curve of the quick
Pediatric Logistic Organ Dysfunction-2 score on day 1 was 0.82 (0.76-0.87) with
systolic blood pressure or mean blood pressure; calibration p value was 0.89 and
0.72, respectively. A score greater than or equal to 2 reflected a mortality risk
greater than or equal to 19.8% with systolic blood pressure and greater than or
equal to 15.9% with mean blood pressure. CONCLUSION: Among children admitted to
PICU with suspected infection, Pediatric Logistic Organ Dysfunction-2 score on
day 1 was highly predictive of PICU mortality suggesting its use to standardize
definitions and diagnostic criteria of pediatric sepsis. Further studies are
needed to determine the usefulness of the quick Pediatric Logistic Organ
Dysfunction-2 score on day 1 outside of the PICU.
PMID- 28492403
TI - Pediatric In-Hospital Acute Respiratory Compromise: A Report From the American
Heart Association's Get With the Guidelines-Resuscitation Registry.
AB - OBJECTIVES: The main objectives of this study were to describe in-hospital acute
respiratory compromise among children (< 18 yr old), and its association with
cardiac arrest and in-hospital mortality. DESIGN: Observational study using
prospectively collected data. SETTING: U.S. hospitals reporting data to the "Get
With The Guidelines-Resuscitation" registry. PATIENTS: Pediatric patients (< 18
yr old) with acute respiratory compromise. Acute respiratory compromise was
defined as absent, agonal, or inadequate respiration that required emergency
assisted ventilation and elicited a hospital-wide or unit-based emergency
response. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome
was in-hospital mortality. Cardiac arrest during the event was a secondary
outcome. To assess the association between patient, event, and hospital
characteristics and the outcomes, we created multivariable logistic regressions
models accounting for within-hospital clustering. One thousand nine hundred fifty
two patients from 151 hospitals were included. Forty percent of the events
occurred on the wards, 19% in the emergency department, 25% in the ICU, and 16%
in other locations. Two hundred eighty patients (14.6%) died before hospital
discharge. Preexisting hypotension (odds ratio, 3.26 [95% CI, 1.89-5.62]; p <
0.001) and septicemia (odds ratio, 2.46 [95% CI, 1.52-3.97]; p < 0.001) were
associated with increased mortality. The acute respiratory compromise event was
temporally associated with a cardiac arrest in 182 patients (9.3%), among whom
46.2% died. One thousand two hundred eight patients (62%) required tracheal
intubation during the event. In-hospital mortality among patients requiring
tracheal intubation during the event was 18.6%. CONCLUSIONS: In this large,
multicenter study of acute respiratory compromise, 40% occurred in ward settings,
9.3% had an associated cardiac arrest, and overall in-hospital mortality was
14.6%. Preevent hypotension and septicemia were associated with increased
mortality rate.
PMID- 28492405
TI - A Case-Control Analysis of Postoperative Fluid Balance and Mortality After
Pediatric Cardiac Surgery.
AB - OBJECTIVES: A positive fluid balance after cardiac surgery may be associated with
poor outcomes; however, previous studies looking at this association have been
limited by the number of deaths in the study population. Our primary aim was to
determine the relationship between postoperative cumulative fluid balance and
mortality in cardiac surgical patients. Secondary aims were to study the
association between fluid balance and duration of mechanical ventilation,
intensive care and hospital length of stay. DESIGN: Case-control study. SETTING:
A 30-bed multidisciplinary PICU. PATIENTS: All patients admitted to the PICU
following cardiac surgery from 2010 to 2014. INTERVENTIONS: Deaths during PICU
admission following cardiac surgery (cases) were matched 1:3 with children who
survived to PICU discharge (controls) using the following criteria: age at
surgery (within a 20% age range), Risk Adjusted Congenital Heart Surgery (RACHS
1) category, and year of admission. MEASUREMENTS AND MAIN RESULTS: Of 1,996
eligible children, 46 died (2.3%) of whom 45 (98%) were successfully matched.
Cumulative fluid balance on days 2 and 7 was not associated with PICU mortality.
On multivariable analysis, factors associated with mortality were cardiopulmonary
bypass time (per 10-min increase, odds ratio [95% CI], 1.06 [1.00-1.12]; p =
0.03), extracorporeal membrane oxygenation requirement within 3 days (46.6 [9.47
230.11]; p < 0.001), peak serum chloride (mmol/L) in the first 48 hours (1.12
[1.01-1.23]), and time to start peritoneal dialysis after surgery (in comparison
to no peritoneal dialysis, odds ratio [95% CI] in those started on early
peritoneal dialysis was 1.07 [0.33-3.41]; p = 0.90 and in late peritoneal
dialysis 3.65 [1.21-10.99]; p = 0.02). Children with cumulative fluid balance
greater than or equal to 5% by day 2 spent longer on mechanical ventilation
(median [interquartile range], 211 hr [97-539] vs 93 hr [34-225]; p <0.001), in
PICU (11 d [8-26] vs 6 [3-13]; p < 0.001) and in hospital (22 d [13-39] vs 14 d
[8-30]; p = 0.001). CONCLUSIONS: Early fluid overload is not associated with
mortality. However, it is associated with increased duration of mechanical
ventilation and PICU length of stay. Early peritoneal dialysis commencement
(compared with late peritoneal dialysis) after surgery was associated with
decreased mortality.
PMID- 28492407
TI - The spleen not taken: Differences in management and outcomes of blunt splenic
injuries in teenagers cared for by adult and pediatric trauma teams in a single
institution.
AB - BACKGROUND: Nonoperative management (NOM) of blunt splenic injury, initially
touted for the care of pediatric patients, has become the standard of care for
stable trauma patients of all ages. In our institution, trauma patients younger
than 16 years are managed by the pediatric surgery service and patients 16 years
or older are managed by the adult trauma service. Angioembolization is routinely
used for adults with blunt splenic injury but rarely used for pediatric patients.
A retrospective chart review was performed to determine if more liberal use of
angioembolization increases the success rate of NOM of blunt splenic injury in
adolescents. METHODS: Using our institutional trauma registry, we performed a
retrospective chart review of 13- to 18-year-olds admitted with blunt splenic
injury from 2007 to 2015. One hundred thirty-three patients were identified; 59
were 13- to 15-year-olds and cared for by the Pediatric Trauma service, whereas
74 were 16- to 18-year-olds and cared for by the Adult Trauma service. The
cohorts were compared with respect to imaging performed, grade of injury, Injury
Severity Score, presence of active extravasation or pseudoaneurysm, interventions
performed, blood transfused, intensive care unit days, length of stay,
complications, and 30-day mortality rates. RESULTS: There were no significant
differences in Injury Severity Score, incidence of active extravasation or
pseudoaneurysm identified on computed tomography, or grade of injury between the
two cohorts. More patients underwent angioembolization in the "adult" group (p =
0.001) with no difference in the success rate of NOM (p = 0.117). The overall
failure rate of NOM of high-grade injuries was only 4.1%. CONCLUSION: Failure of
NOM in high-grade injuries is rare; as a result, the number needed to treat with
prophylactic angioembolization would be around 37 patients, resulting in undue
risk to many patients with no therapeutic benefit. No improvement in failure rate
was seen with aggressive angioembolization, though a larger sample size is needed
to rule out type 2 error. LEVEL OF EVIDENCE: Therapeutic, level IV.
PMID- 28492404
TI - Trend and Outcomes of Video Laryngoscope Use Across PICUs.
AB - OBJECTIVE: Video (indirect) laryngoscopy is used as a primary tracheal intubation
device for difficult airways in emergency departments and in adult ICUs. The use
and outcomes of video laryngoscopy compared with direct laryngoscopy has not been
quantified in PICUs or cardiac ICUs. DESIGN: Retrospective review of
prospectively collected observational data from a multicenter tracheal intubation
database (National Emergency Airway Registry for Children) from July 2010 to June
2015. SETTING: Thirty-six PICUs/cardiac ICUs across the United States, Canada,
Japan, New Zealand, and Singapore. PATIENTS: Any patient admitted to a PICU or a
pediatric cardiac ICU and undergoing tracheal intubation. INTERVENTIONS: Use of
direct laryngoscopy versus video laryngoscopy for tracheal intubation.
MEASUREMENTS AND MAIN RESULTS: There were 8,875 tracheal intubations reported in
the National Emergency Airway Registry for Children database, including 7,947
(89.5%) tracheal intubations performed using direct laryngoscopy and 928 (10.5%)
tracheal intubations performed using video laryngoscopy. Wide variability in
video laryngoscopy use exists across PICUs (median, 2.6%; range, 0-55%). Video
laryngoscopy was more often used in older children (p < 0.001), in children with
history of a difficult airway (p = 0.01), in children intubated for ventilatory
failure (p < 0.001), and to facilitate the completion of an elective procedure (p
= 0.048). After adjusting for patient-level covariates, a secular trend, and site
level variance, the use of video laryngoscopy significantly increased over a 5
year period compared with fiscal year 2011 (odds ratio, 6.7; 95% CI, 1.7-26.8 for
fiscal year 2014 and odds ratio, 11.2; 95% CI, 3.2-38.9 for fiscal year 2015).
The use of video laryngoscopy was independently associated with a lower
occurrence of tracheal intubation adverse events (adjusted odds ratio, 0.57; 95%
CI, 0.42-0.77; p < 0.001) but not with a lower occurrence of severe tracheal
intubation adverse events (adjusted odds ratio, 0.86; 95% CI, 0.56-1.32; p =
0.49) or fewer multiple attempts at endotracheal intubation (adjusted odds ratio,
0.93; 95% CI, 0.71-1.22; p = 0.59). CONCLUSIONS: Using National Emergency Airway
Registry for Children data, we described patient-centered adverse outcomes
associated with video laryngoscopy compared with direct laryngoscopy for tracheal
intubation in the largest reported international cohort of children to date. Data
from this study may be used to design sufficiently powered prospective studies
comparing patient-centered outcomes for video laryngoscopy versus direct
laryngoscopy during endotracheal intubation.
PMID- 28492408
TI - THE 2017 JOINT INTERNATIONAL CONGRESS OF ILTS, ELITA & LICAGE.
PMID- 28492409
TI - Papillary Carcinoma Arising in a Thyroglossal Duct Cyst.
PMID- 28492410
TI - DEXAMETHASONE INTRAVITREAL IMPLANT FOR CHOROIDAL NEOVASCULARIZATION DURING
PREGNANCY.
AB - PURPOSE: To describe the management of active choroidal neovascularization (CNV)
during pregnancy with the use of a dexamethasone intravitreal implant (DXI)
(Ozurdex). METHODS: Case series of active CNV treated with DXI with at least 12
month follow-up retrospectively analyzed at 2 high-volume referral centers in
France. Medical records and multimodal macular imaging were evaluated. RESULTS:
Three eyes of 3 patients (age 30.0 +/- 3.6 years) were included. One case of
idiopathic CNV and two cases of CNV secondary to multifocal choroiditis were
analyzed. Mean follow-up was 20.6 +/- 4.0 months (range, 16-23 months). The DXI
was given at second trimester of established pregnancy in all cases. Mean central
retinal thickness decreased from 359 +/- 53 MUm to 301 +/- 17 MUm 1 month after
DXI and remained stable up to 12 months of follow-up. Visual improvement in all
cases was observed (mean 10 letters; range, 5-30 letters) 1 month after DXI and
remained stable/increased up to 12-month follow-up (mean 22 letters; range, 10-30
letters). All patients had an uneventful prenatal course and delivered a healthy
full-term infant. CONCLUSION: In the authors' experience, a single DXI revealed
safe and effective in CNV treatment during pregnancy.
PMID- 28492411
TI - Advanced glycation end products among patients maintained on antipsychotics.
AB - The aim of this study was to measure advanced glycation end products (AGEs) among
participants maintained on antipsychotics using the AGE Reader and to compare
them with controls from the general population. Participants maintained on
antipsychotics for at least 6 months were recruited from the Psychiatry
Department at Rumailah Hospital, Doha, Qatar. Healthy controls were recruited
from the primary healthcare centers in Doha, Qatar. AGEs of a total of 86
participants (48 patients and 38 controls) were recorded. Among the group
maintained on antipsychotics, women, smokers, and Arabs had significantly higher
AGEs levels compared with men, nonsmokers, and non-Arabs, respectively (P<0.05).
The levels of AGEs were higher among the group of patients maintained on
antipsychotics in comparison to controls; however, the difference did not reach
statistical significance. This is the first study to examine AGEs in patients
maintained on antipsychotics. Our findings showed that such patients do not
differ significantly from controls comparing AGEs levels. Future investigations
might need to consider recruiting a larger sample size using a prospective
design.
PMID- 28492412
TI - Patients in prehospital transport to the emergency department: a cohort study of
risk factors for 7-day mortality.
AB - BACKGROUND: Ambulance transfer is the first contact with the healthcare system
for many patients in emergency conditions.We aimed to identify prognostic risk
factors accessible in the prehospital phase that indicate an increased risk of 7
day mortality. PATIENTS AND METHODS: We included patients aged 18 years or older,
transferred by ambulance to the emergency department at Odense University
Hospital, from 1 April 2012 to 30 September 2014. We carried out multivariate
logistic regressions, adjusted for age and sex, to describe the relationship
between vital sign values recorded in the prehospital setting and 7-day
mortality. RESULTS: A total of 32 076 ambulance transfers were recorded. Of
these, 20 328 were first-time transfers, including 2692 that received assistance
from a physician-staffed mobile emergency care unit (MECU). The 7-day mortality
was 5.3% [95% confidence interval (CI): 5.0-5.6]. The risk of death increased
with age. The odds ratios (ORs) were 2.0 (95% CI: 1.1-3.5) for ages 30-44 years
and 7.3 (95% CI: 4.5-11) for ages 45-69 years compared with the 18-29-year-olds.
All abnormal vital sign values were associated with increased 7-day mortality.
Glasgow Coma Score of less than 14 had the strongest association (OR: 17, 95% CI:
14.7-19.7). MECU assistance showed an adjusted OR of 5.3 (95% CI: 4.6-6.1).
CONCLUSION: The overall 7-day mortality was 5.3%, but differed in the two
subgroups, with 15.4% in the MECU-assisted ambulance transfers and 3.8% in non
MECU-assisted transfers. Older age and Glasgow Coma Scores below 14 were the
strongest of factors associated significantly with 7-day mortality.
PMID- 28492413
TI - Mentoring in Nursing: An Integrative Review of Commentaries, Editorials, and
Perspectives Papers.
AB - Although pivotal to mentoring success, scant data on mentoring relationships
continue to hamper the application of mentoring programs in nursing education. To
address this gap and circumnavigate mentoring's context-specific nature, this
narrative review analyzes the perspectives and opinions of nurse mentors and
mentees. The aim is to identify common themes in their mentoring experiences to
better nurture effective mentoring relationships and programs in nursing.
PMID- 28492414
TI - Motivated Strategies for Learning in Accelerated Second-Degree Nursing Students.
AB - Students in a second-degree accelerated BSN program experience a rigorous
curriculum and fast-paced introduction to the nursing profession. This study
examined the relationships among self-esteem, motivation, learning strategies,
demographic characteristics, and academic achievement. The results indicated that
all of the students had good self-esteem; some demographic characteristics
influenced the type of motivation and learning strategies they endorsed but did
not influence their current academic performance.
PMID- 28492415
TI - Anticoagulation Control in Patients With Ventricular Assist Devices.
AB - Anticoagulation control has been associated with risk of thromboembolism and
hemorrhage. Herein, we explore the relationship between anticoagulation control
achieved in left ventricular assist device (LVAD) patients and evaluate the
association with risk of thromboembolism and hemorrhage. Patients (19 years old
or older) with a continuous flow LVAD placed from 2006 to 2012. Percent time
spent in target range (PTTR) for international normalized ratio (INR) was
estimated with target range of 2.0-3.0. Proportion of time spent in target range
was categorized into PTTR > 60%, PTTR >= 50 < 60%, and PTTR < 50%. The
relationship between PTTR and thromboembolism and hemorrhage was assessed. One
hundred fifteen participants contributed 624.5 months of follow-up time. Only 20%
of patients achieved anticoagulation control (PTTR > 60% for INR range of 2-3).
After adjusting for chronic kidney disease, history of diabetes, history of
atrial fibrillation, and age at implant, compared with patients with PTTR < 50%,
the relative risk of thromboembolism in patients with PTTR >= 60% (hazard ratio
[HR]: 0.37; 95% confidence interval [CI]: 0.14-0.96; p = 0.042) was significantly
lower, but not for patients with a PTTR of >= 50 < 60% (HR: 0.21; 95% CI: 0.02
1.82; p = 0.16). The relative risk for hemorrhage was also significantly lower
among patients with a PTTR >= 60% (HR: 0.45; 95% CI: 0.21-0.98; p = 0.045), but
not among those with PTTR of >= 50 < 60% (HR: 0.47; 95% CI: 0.14-1.56; p = 0.22).
This current study demonstrates that LVAD patients remain in the INR target range
an average of 42.9% of the time. To our knowledge, this is the first report with
regard to anticoagulation control as assessed by PTTR and its association with
thromboembolism, hemorrhage, or death among patients with ventricular assist
devices (VADs).
PMID- 28492416
TI - Cannabinoid 1 receptor blockade in the dorsal hippocampus prevents the
reinstatement but not acquisition of morphine-induced conditioned place
preference in rats.
AB - The cannabinoid 1 receptors (CB1Rs) signaling is strongly linked to conditioned
rewarding effects of opiates. Learned associations between environmental contexts
and discrete cues and drug use play an important role in the maintenance and/or
relapse of morphine addiction. Although previous studies suggest that context
dependent morphine treatment alters endocannabinoid signaling and synaptic
plasticity in the hippocampus, the role of endocannabinoid in morphine
conditioned place preference (CPP) and reinstatement remains unknown. In the
present study, we found daily escalating doses of morphine induce significant CPP
in rats. After the extinction of CPP, a priming dose of morphine was sufficient
to reinstate morphine CPP and was associated with the elevated CB1R levels
compared with saline control groups, suggesting upregulation of CB1R pathway in
the hippocampus contribute to the reinstatement of morphine CPP. By using a
pharmacological inhibitor of CB1R administered into the dorsal hippocampus, we
showed that blockade of CB1R signaling did not alter the morphine CPP acquisition
but inhibited the reinstatement of morphine CPP. In addition, no effects were
induced upon CB1R blockade in the prefrontal cortex on reinstatement of morphine
CPP. These studies reveal region-specific effects of hippocampal blockade of CB1R
signaling pathway on the reinstatement of morphine CPP.
PMID- 28492417
TI - Cognitive control in children with learning disabilities: neuromarker for
deficient executive functions.
AB - The neural underpinnings of learning disabilities (LD) are still not known.
Recent discussions focus over whether domain-specific and/or domain-unspecific
reasons might be responsible for LD either alone or in combination with each
other. This study applied standard nonverbal Go-NoGo tasks (visual continuous
performance test) to LD and healthy control children to examine whether they show
deficient executive functions. During this Go-NoGo task, electroencephalogram was
measured in addition to reaction times, hits, omissions, and commissions to the
Go and NoGo stimuli. It was shown that children with LD reacted slower with
variable responses to Go stimuli and made more omission errors in comparison with
the healthy control children. The analysis of the event-related potential
indicated that the deficient behavior in this task is associated with smaller -
and in part nonexistent - P3d amplitudes. This neural activation indicates a
different neural activation pattern during action inhibition in LD children. The
neural networks involved in controlling action inhibition are mostly located in
frontal brain areas, for which it has been shown that children with LD show
neural activation deficiencies. This is possibly a consequence of a maturational
delay of the frontal cortex.
PMID- 28492418
TI - Clinical Feasibility of Free-Breathing Dynamic T1-Weighted Imaging With Gadoxetic
Acid-Enhanced Liver Magnetic Resonance Imaging Using a Combination of Variable
Density Sampling and Compressed Sensing.
AB - OBJECTIVES: The purpose of the study was to investigate the clinical feasibility
of free-breathing dynamic T1-weighted imaging (T1WI) using Cartesian sampling,
compressed sensing, and iterative reconstruction in gadoxetic acid-enhanced liver
magnetic resonance imaging (MRI). MATERIALS AND METHODS: This retrospective study
was approved by our institutional review board, and the requirement for informed
consent was waived. A total of 51 patients at high risk of breath-holding failure
underwent dynamic T1WI in a free-breathing manner using volumetric interpolated
breath-hold (BH) examination with compressed sensing reconstruction (CS-VIBE) and
hard gating. Timing, motion artifacts, and image quality were evaluated by 4
radiologists on a 4-point scale. For patients with low image quality scores (<3)
on the late arterial phase, respiratory motion-resolved (extradimension [XD])
reconstruction was additionally performed and reviewed in the same manner. In
addition, in 68.6% (35/51) patients who had previously undergone liver MRI, image
quality and motion artifacts on dynamic phases using CS-VIBE were compared with
previous BH-T1WIs. RESULTS: In all patients, adequate arterial-phase timing was
obtained at least once. Overall image quality of free-breathing T1WI was 3.30 +/-
0.59 on precontrast and 2.68 +/- 0.70, 2.93 +/- 0.65, and 3.30 +/- 0.49 on early
arterial, late arterial, and portal venous phases, respectively. In 13 patients
with lower than average image quality (<3) on the late arterial phase, motion
resolved reconstructed T1WI (XD-reconstructed CS-VIBE) significantly reduced
motion artifacts (P < 0.002-0.021) and improved image quality (P < 0.0001-0.002).
In comparison with previous BH-T1WI, CS-VIBE with hard gating or XD
reconstruction showed less motion artifacts and better image quality on
precontrast, arterial, and portal venous phases (P < 0.0001-0.013). CONCLUSIONS:
Volumetric interpolated breath-hold examination with compressed sensing has the
potential to provide consistent, motion-corrected free-breathing dynamic T1WI for
liver MRI in patients at high risk of breath-holding failure.
PMID- 28492420
TI - Helminthic Therapy: A New Era in Immune-Mediated Diseases.
PMID- 28492419
TI - Seroprevalence of antibodies and antigens against hepatitis A-E viruses in
refugees and asylum seekers in Germany in 2015.
AB - BACKGROUND: Migration because of miscellaneous political crises in countries in
the Middle East and Africa is a global challenge for whole Europe from an
economic, social, and public health view. There is an urgent need to generate
comprehensive, evidence-based data to expedite further screening and vaccination
strategies. METHODS: A total of 604 individuals ranging in age from 2 to 68 years
who enrolled at a single reception center were tested for the prevalence of
serologic markers for hepatitis virus types A, B, C, D, and E (HAV, HBV, HCV,
HDV, HEV), respectively. RESULTS: Anti-HAV antibody prevalence was 91.2 and 70.3%
in children younger than 18 years of age. The prevalence of anti-HEV antibodies
was 20.1% among the individuals. 3.0% were positive for hepatitis B surface
antigen, whereas 15.2% tested positive for anti-hepatitis B core antigen. None of
the refugees tested positive for anti-HDV. 14.1% of refugees were vaccinated
against hepatitis B and had a protective anti-hepatitis B surface level of at
least 10 mIU/ml. Significant differences in vaccination status were found between
the regions (Eastern Mediterranean Region with 77/482 (16.0%; 95% confidence
interval=12.7-19.3%) versus African Region with 1/55 (1.8%; 95% confidence
interval=0-5.0%). The prevalence of anti-HCV antibodies was 1.2% (n=7), with 0.7%
HCV RNA positivity; 16.7% of hepatitis B surface antigen-positive individuals
were HCV coinfected (n=3). CONCLUSION: The prevalence of refugees with previous
exposure to hepatitis viruses was higher than that in the general German
population, but lower than in other migrant populations in Germany. The
vaccination status against hepatitis B was poor.
PMID- 28492421
TI - Description of Malignancy Rates in Childhood- and Adult-Onset Systemic Lupus
Erythematous by Proportional Meta-analysis.
AB - OBJECTIVE: Describe malignancy rates in childhood onset and adult onset systemic
lupus erythematous (SLE) by proportional meta-analysis. METHODS: Two reviewers
screened data from PubMed (1966-2015), EMBASE (1980-2015), and LILACS (1982-2015)
for SLE-associated malignancy. Proportional meta-analysis with a random-effects
model and 95% confidence intervals (CIs) were calculated according to SLE onset
age and mean follow-up time. Statistical difference was defined by 95% CI
overlap. RESULTS: Overall the malignancy rate reported in 30 case series with
96,578 subjects was 3.4% (95% CI, 0.0260-0.0442; I = 97.6%; P < 0.0001). The
malignancy rate was 4.2% (95% CI, 0.0318-0.0531; I = 98%; P < 0.0001) in 25 adult
onset SLE series, compared with 0.5% (95% CI, 0.0003-0.0154; I = 62.6%; P = 0.03)
in 5 childhood-onset SLE series. Overall, in those with less than 5 years' follow
up, the malignancy rate was 2.8% (95% CI, 0.013-0.047; I = 91%; P < 0.0001)
compared with 3.6% (95% CI, 0.0226-0.0531; I = 98.3%; P < 0.0001) in those with
more than 5 years' follow-up, which was not significant, with 95% CI overlap.
CONCLUSIONS: The meta-analysis indicated lower malignancy rates in pediatric
onset SLE compared with adult-onset SLE, but accrued data from childhood-onset
SLE are still needed.
PMID- 28492422
TI - Increasing Patient-Clinician Concordance About Medical Error Disclosure Through
the Patient TIPS Model.
AB - OBJECTIVE: To test whether an educational model involving patients and family
members (P/F) in medical error disclosure training for interprofessional
clinicians can narrow existing gaps between clinician and P/F views about
disclosure. METHOD: Parallel presurveys/postsurveys using Likert scale questions
for clinicians and P/F. RESULTS: Baseline surveys were completed by 91% (50/55)
of clinicians who attended the workshops and 74% (65/88) of P/F from a hospital
patient and family advisory council. P/F's baseline views about disclosure were
significantly different from clinicians' in 70% (7/10) of the disclosure
expectation items and 100% (3/3) of the disclosure vignette items. For example,
compared with clinicians, P/F more strongly agreed that "patients want to know
all the details of what happened" and more strongly disagreed that "patients find
explanation(s) more confusing than helpful." In the medication error vignette,
compared with clinicians, P/F more strongly agreed that the error should be
disclosed and that the patient would want to know and more strongly disagreed
that disclosure would do more harm than good (all P < 0.05). After the workshop,
P/F and clinician views about information sharing, fallibility, truth telling,
and threshold for disclosure showed greater concordance, with significant
differences remaining in less than half of the expectation items and none of the
vignette responses. DISCUSSION: Even with self-selecting clinicians,
collaborative learning with P/F highlights important differences in patient and
clinician baseline perspectives about medical error disclosure and brings patient
and clinicians views closer together.
PMID- 28492423
TI - A Survey of the Opinion and Experience of UK Dentists Part 3: An Evidence-Based
Protocol of Surgical Risk Management Strategies in the Mandible.
AB - BACKGROUND: Implant surgery in the mandible can cause serious complications that
can be life threatening. The incidence and cause of iatrogenic trigeminal nerve
injury (TNI) related to dental implant surgery was investigated in a survey of
the opinion and experience of the UK dentists and reported by the authors in part
1 of this series of articles. Part 2 reported on the risk assessment and
management of implant-related inferior alveolar nerve (IAN), mental nerve (MN),
and lingual nerve (LN) injuries. This article evaluates the significance of these
findings and recommends an evidence-based protocol of risk management strategies
to reduce the risk of TNI related to dental implant surgery. METHODS: A survey
was distributed among 405 dentists attending an Association of Dental
Implantology (ADI) congress, of which 187 completed the survey. RESULTS: In this
study, the strategies to manage the risk of TNI included unilateral staging of
implant placement (57%) and identification the MN when placing implants (43%).
Twelve percent used drill stops when operating in the mandible. Nineteen dentists
used steroids (eg, dexamethasone) routinely preoperatively and postoperatively.
Twenty-six dentists used basic cone beam computed tomography minimally invasive
techniques, and 70% encountered a large anterior loop of the IAN. Most dentists
(76%) allowed a 2- to 4-mm safety zone radiologically above the IAN when placing
implants, and over half of the responders (56%) used implants that were 10 mm in
length. CONCLUSION: Given the elective nature of implant surgery, TNI should be
fully avoidable. The evidence suggest that TNI can be minimized with meticulous
attention to accurate assessment and surgical planning as well as carrying out
the surgery with a high degree of precision. In part 3 of their series of
articles, the authors presented an evidence-based protocol that comprises
preoperative, intraoperative, and postoperative risk management strategies for
dental implant surgical procedures in the mandible.
PMID- 28492424
TI - A New Highly Hydrophilic Electrochemical Implant Titanium Surface: A Histological
and Biomechanical In Vivo Study.
AB - PURPOSE: The aim was to compare the osseointegration degree and secondary implant
stability between implants with different surface treatments. MATERIALS AND
METHODS: A novel electrochemical treatment was applied to modify the sandblasted
and acid-etched surface (SLA) to obtain the new hydrophilic Feeling (FEL) surface
presenting a highly soluble and homogenous film made of calcium and phosphorus
nanocrystals. Twenty 3.8 * 10-mm dynamix implants (Cortex) were inserted in sheep
iliac crests. Sheep were killed after 2 months. Bone-to-implant contact
percentage (%BIC) and biomechanical parameters, such as implant stability
quotient (ISQ) and value of actual micromotion (VAM), were evaluated for each
implants. RESULTS: No implant failures were observed. Implants of test group
showed %BIC value 30% higher in respect with control group (P = 0.001). No
statistical differences were detected between the 2 groups in VAM and ISQ values.
CONCLUSION: Both surface treatments were highly osteoconductive because they were
able to significantly increase the bone density onto implant surface in respect
with that in which they were inserted (D4 bone density). The hydrophilic FEL
surface demonstrated an increase of about 216% in BIC in respect with host bone
density and an additional 30% more in respect with SLA surface. Faster
osseointegration process is desirable in case of early implant loading protocol.
PMID- 28492425
TI - Identifying Patient and Provider-specific Gaps in Care Among Patients With
Hepatitis B.
AB - GOALS: To examine patient, provider, and health system barriers to clinical
follow-up among US veterans with chronic hepatitis B virus (HBV). BACKGROUND:
Studies have demonstrated deficiencies in clinical care and follow-up in HBV;
however, patient, provider, and health-system barriers in non-Asian populations
are understudied. STUDY: A retrospective cohort of 517 US veterans with chronic
HBV at 3 diverse Veterans Affairs sites from 1999 to 2015. Laboratory testing and
completion of clinical appointments were collected for 2 years following initial
presentation. RESULTS: Among HBV patients, 36% had drug abuse, 41% alcohol
misuse, and 45% had psychiatric disorders. Patients had an average of 4.4 primary
care visits within 2 years of the index hepatitis B surface antigen positive
result, 38% had psychiatry visits, 21% had a psychiatric hospitalization; 26% saw
gastroenterology/hepatology specialists. Within 1 year of the index hepatitis B
surface antigen positive result, 75% had alanine aminotransferase testing, 14%
had HBV entered into the problem list, and 8% had serologic confirmation. In
multivariable analyses, cirrhosis [odds ratio (OR)=3.42; 95% confidence interval
(CI), 1.84-6.36] was associated with higher odds of appropriate laboratory
testing, alcohol misuse (OR=0.45; 95% CI, 0.29-0.80) was associated lower odds.
Cirrhosis (OR=2.03; 95% CI, 1.11-3.72) and >=2 primary care visits per year
(OR=1.06; 95% CI, 1.01-1.11) were associated with higher odds of completing
gastroenterology/hepatology consultation, whereas >=1 psychiatric hospitalization
in 2 years was associated with lower odds (OR=0.53; 95% CI, 0.34-0.82).
CONCLUSIONS: In a diverse cohort of veterans with high psychiatric comorbidity
and substance abuse, important patient and provider factors influence appropriate
follow-up care. Future studies should evaluate the impact of provider education
and care coordination strategies in HBV.
PMID- 28492426
TI - Trichotillomania in Attention-Deficit/Hyperactivity Disorder Under
Methylphenidate Treatment.
PMID- 28492427
TI - QUANTITATIVE OPTICAL COHERENCE TOMOGRAPHY ANALYSIS OF RETINAL DEGENERATIVE
CHANGES IN DIABETIC MACULAR EDEMA AND NEOVASCULAR AGE-RELATED MACULAR
DEGENERATION.
AB - PURPOSE: To investigate the relationship of the pre-anti-vascular endothelial
growth factor (VEGF) retinal tissue area (RTA) and optical density (ODRT) of the
retinal optical slice portion located in the central subfield, and their ratio
(RTA/ODRT), in the presence of diabetic macular edema or of inraretinal cystic
fluid in neovascular age-related macular degeneration, to central retinal
thickness and best-corrected visual acuity after anti-VEGF treatment with ME
resolution. METHODS: The optical coherence tomography images and medical records
of 33 patients (41 eyes) with neovascular age-related macular degeneration, 15
(21 eyes) with diabetic macular edema and 9 healthy individuals (15 eyes) were
retrospectively analyzed. RTA, ODRT, and RTA/ODRT were calculated on pre-anti
VEGF B-scan images. Spearman rank correlation was used to assess the relationship
of central retinal thickness and best-corrected visual acuity after anti-VEGF
treatment with the variables under study. RESULTS: Pre-anti-VEGF RTA was
positively correlated with post-anti-VEGF central retinal thickness (rho = 0.76;
P < 0.001) and best-corrected visual acuity (rho = 0.67; P < 0.001), whereas pre
anti-VEGF ODRT was moderately negatively correlated (rho = -0.26; P = 0.049 and
rho = -0.48; P = 0.001, respectively) and pre-anti-VEGF RTA/ODRT ratio was
strongly positively correlated (rho = 0.75; P < 0.001 and rho = 0.85; P < 0.001,
respectively). The area under curve for RTA/ODRT ratio was 0.93 (P < 0.001), and
the cut-off value for post-anti-VEGF LogMAR best-corrected visual acuity of 0.4
(20/50 Snellen equivalent) or worse was 1,406.7 MUm/U (sensitivity: 0.94;
specificity: 0.78). CONCLUSION: Both RTA and ODRT, or, preferably, RTA/ODRT ratio
alone can be used as predictors of functional and anatomic outcomes in patients
with diabetic macular edema or neovascular age-related macular degeneration
treated with anti-VEGF therapy.
PMID- 28492428
TI - A PROSPECTIVE, RANDOMIZED TRIAL COMPARING PLAIN GUT TO POLYGLACTIN 910 (VICRYL)
SUTURES FOR SCLEROTOMY CLOSURE AFTER 23-GAUGE PARS PLANA VITRECTOMY.
AB - PURPOSE: To report a prospective, randomized comparative study assessing clinical
outcomes of plain gut versus polyglactin 910 (PG910) sutures for sclerotomy
closure after 23-gauge pars plana vitrectomy. METHODS: A single-masked,
randomized, prospective study was undertaken with 49 eyes of 49 patients
undergoing 23-gauge pars plana vitrectomy randomized to sclerotomy closure with
either plain gut suture, PG910 (Vicryl) suture or a combination of the two.
Assessment was based on both a postoperative pain scale and a standardized
assessment of scleral inflammation at each suture site. RESULTS: No wound leakage
was noted postoperatively in any patient. Across all groups, scleral inflammation
was significantly higher at the PG910 suture sites compared with the plain gut
suture sites at both the 1-week (P = 0.04) and 1-month postoperative visits (P <
0.001). Patients with PG910 sutures reported greater pain at the 1-month
postoperative visit than those with plain gut sutures (P = 0.018). CONCLUSION:
This prospective study suggests improved tolerability and reduced inflammation
using plain gut suture compared with an 8-0 PG910 suture to close 23-gauge
sclerotomies.
PMID- 28492429
TI - THREE-DIMENSIONAL ANALYSIS OF SUBMACULAR PERFORATING SCLERAL VESSELS BY ENHANCED
DEPTH IMAGING OPTICAL COHERENCE TOMOGRAPHY.
AB - PURPOSE: To analyze submacular perforating scleral vessels (PSVs) using enhanced
depth imaging spectral domain optical coherence tomography (EDI-SDOCT). METHODS:
Twenty-two eyes of 11 healthy women were included in this retrospective study.
Central EDI-SDOCT scans (3 * 4.5 * 1.9 mm, 13.5 mm scan area) were acquired and
postprocessed by denoising, manual sclera segmentation, and PSV investigated by
five graders. RESULTS: Mean age was 22.4 +/- 6.2 years. Mean refractive error was
-0.44 +/- 0.8 diopters. Mean axial length was 23.08 +/- 0.63 mm. The coefficient
of agreement for grading was good. Mean number of submacular PSVs was 0.33 +/-
0.2 per mm (range from 0 to 9 per eye). Subfield analysis showed 0.2 +/- 0.5
(range 0-2) and 2.1 +/- 1.8 (range 0-7) vessels, respectively, for central 1-mm
diameter and 3-mm diameter. Quadrant analysis showed 0.7 +/- 0.9, 0.5 +/- 0.9,
0.3 +/- 0.6, and 0.4 +/- 0.6 vessels, respectively for superior, inferior, nasal,
and temporal quadrants. Total number of PSV showed no significant side difference
(median difference 0.5, confidence interval -3.0 to 3.0, P = 0.94) or an
influence of axial length (P = 0.16). CONCLUSION: This is the first description
of three-dimensional EDI-SDOCT visualization of submacular PSV in healthy eyes.
This method allows for in vivo imaging of a critical component of outer retinal
perfusion at the posterior pole.
PMID- 28492430
TI - SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN ENDOGENOUS CANDIDA
ENDOPHTHALMITIS AND THEIR CLINICAL RELEVANCE.
AB - PURPOSE: To describe vitreal, retinal, and choroidal features of eyes affected by
Endogenous candida endophthalmitis (ECE) analyzed by spectral domain optical
coherence tomography (SD-OCT) and to evaluate their clinical impact. METHODS:
Medical records and SD-OCT images from eyes diagnosed with ECE at four retina and
uveitis tertiary referral centers were retrospectively evaluated. Spectral domain
optical coherence tomography images were analyzed to evaluate the structural
changes occurring in the vitreous, the retina, and the choroid in areas involved
by ECE. Baseline and final best-corrected visual acuity were correlated with SD
OCT findings. RESULTS: Fifteen eyes from nine patients were enrolled. Vitreous
involvement (vitreous cells, posterior hyaloid thickening) was detected in 13/15
eyes. Peculiar hyper-reflective preretinal aggregates obscuring the underlying
retina because of a shadowing effect ("rain-cloud" sign) were noticed in all eyes
with vitreous involvement. Two patterns of retinal and choroidal findings were
identified: the first (six eyes) confined within the inner retinal layers
(Intraretinal Pattern), the second (nine eyes) involving both retina (full
thickness) and choriocapillaris (Chorioretinal Pattern). None of the eyes showed
both patterns. None of the eyes, regardless the pattern, showed choroidal
thickening. Baseline best-corrected visual acuity was not associated with OCT
pattern (P = 0.09). On the contrary, final best-corrected visual acuity was
significantly higher in patients showing Intraretinal Pattern (~20/25, 0.06 +/-
0.08 LogMAR) than in subjects with Chorioretinal Pattern (~20/50, 0.44 +/- 0.30
LogMAR) (P = 0.01). CONCLUSION: Endogenous candida endophthalmitis showed
peculiar features on SD-OCT. Two distinct patterns of chorioretinal involvement
influencing the final best-corrected visual acuity were identified. Spectral
domain optical coherence tomography could be useful in the diagnosis, management,
and outcome prediction in ECE.
PMID- 28492431
TI - EXPERIENCE USING A 3D HEAD-MOUNTED DISPLAY SYSTEM IN OPHTHALMIC SURGERY.
PMID- 28492432
TI - VASCULAR DISTORTION AND DRAGGING RELATED TO APPARENT TISSUE CONTRACTION IN
MACULAR TELANGIECTASIS TYPE 2.
AB - PURPOSE: To examine the alterations in retinal vascular morphology over an
extended follow-up in eyes with macular telangiectasis Type 2 (MacTel2). METHODS:
Eyes with high-quality digital photographs were evaluated. The geometric
distortion in baseline images required to emulate the follow-up images was
determined and vectors were made that represented the direction and magnitude of
changes, to create a warp field. Optical coherence tomography and optical
coherence tomography angiography evaluation of the retina was performed. RESULTS:
There were 7 eyes of 4 patients, who had a mean age of 70.25 years, which were
followed for a mean of 8.8 years. The eyes showed increasing grayish
opacification in the temporal macula with straightening and displacement of the
macular vessels, even those in the nasal macula. The warp field vectors pointed
to the temporal juxtafoveal macula. There was never any cavitation at the
epicenter of the retinal distortion in any patient, although cavitations were
found around this area. Optical coherence tomography imaging showed a
circumscribed region of hyperreflectivity in the temporal macula. Optical
coherence tomography angiography showed a deep angular condensed network of
vessels within the hyperreflective region. One eye showed marked atrophic changes
including full-thickness macular hole formation, but no increase in graying of
the retina, loss of retinal laminations, pigmentary infiltration, or alteration
in the retinal vessels. CONCLUSION: Tissue contraction with retinal vascular
displacement and contortion seem to be integral aspects of disease manifestation
in MacTel2. The induced vascular changes may lead to secondary effects that
increase morbidity in this disease.
PMID- 28492433
TI - COMBINED PARS PLANA VITRECTOMY AND SCLERAL FIXATION OF AN INTRAOCULAR LENS USING
GORE-TEX SUTURE: One-Year Outcomes.
AB - PURPOSE: To report the 1-year clinical outcomes of combined pars plana vitrectomy
and ab externo scleral fixation of an intraocular lens using Gore-Tex suture.
METHODS: Retrospective, interventional case series. Outcome measures were change
in visual acuity and occurrence of intraoperative and postoperative complications
with minimum follow-up of 1 year. RESULTS: Eighty-four eyes of 83 patients were
identified. The mean best available visual acuity improved from 20/782
preoperatively to 20/65 postoperatively (P < 0.001). The mean follow-up was 598
+/- 183 days (median 533 days, range 365-1,323 days). There were no
intraoperative complications noted. A Bausch & Lomb Akreos AO60 intraocular lens
was implanted in 77 eyes and an Alcon CZ70BD in 7 eyes. Postoperative
complications included transient vitreous hemorrhage in six eyes (7.1%), cystoid
macular edema in four eyes (4.8%), ocular hypertension in three eyes (3.6%),
hyphema in two eyes (2.4%), and transient corneal edema in two eyes (2.4%). There
were no cases of postoperative endophthalmitis, suture erosion/breakage,
hypotony, retinal detachment, suprachoroidal hemorrhage, choroidal detachment,
uveitis-glaucoma-hyphema syndrome, or persistent postoperative inflammation
during the follow-up period. CONCLUSION: Combined pars plana vitrectomy and ab
externo scleral fixation of an intraocular lens with Gore-Tex suture was well
tolerated at a minimum of 1-year follow-up. No suture-related complications were
encountered.
PMID- 28492434
TI - LONGITUDINAL CHANGE OF OUTER NUCLEAR LAYER AFTER RETINAL PIGMENT EPITHELIAL TEAR
SECONDARY TO AGE-RELATED MACULAR DEGENERATION.
AB - PURPOSE: To investigate longitudinal changes of outer nuclear layer (ONL)
thickness in patients with retinal pigment epithelium tears secondary to
neovascular age-related macular degeneration. METHODS: This is an institutional
retrospective interventional case series. Twenty-six eyes of 22 patients with
retinal pigment epithelium tears identified between April 2009 and March 2015.
The patients underwent intravitreal injection of anti-vascular endothelial growth
factor agents as needed. Volume scans of optical coherence tomography at first
diagnosis of tear (baseline) and after 12 months were analyzed. Outer nuclear
layer was segmented, and average ONL thickness inside the tear area, at the
border of the tear, and in areas outside the tear was measured. Change of ONL
thickness. We also explored several factors for their association with ONL
thinning including tear area, number of treatments, and the duration with
persistent subretinal fluid. RESULTS: Thinning of ONL was found in all the
investigated areas (P < 0.01, respectively). Among the investigated factors,
larger tear area was associated with greater ONL thinning outside the tear area
(standardized beta = -0.37, P = 0.030), and younger age was associated with
greater ONL thinning inside the tear area (standardized beta = 0.37, P = 0.041).
CONCLUSION: After an retinal pigment epithelium tear, thinning of ONL occurs in
the area devoid of retinal pigment epithelium and also in adjacent areas. Few
factors were predictive for the degree of ONL thinning. These results provide new
insight in disease progression of this particular neovascular age-related macular
degeneration subphenotype.
PMID- 28492435
TI - CLINICAL FINDINGS OF EYES WITH MACULAR EDEMA ASSOCIATED WITH BRANCH RETINAL VEIN
OCCLUSION REFRACTORY TO RANIBIZUMAB.
AB - PURPOSE: To determine the relationship between the clinical findings and the
response to ranibizumab therapy in eyes with macular edema associated with branch
retinal vein occlusion. METHODS: We reviewed the medical records of 68 patients
with macular edema associated with a branch retinal vein occlusion. The patients
were placed in the refractory group if the central foveal thickness remained more
than 250 MUm throughout the 6-month study period despite the ranibizumab therapy;
otherwise, they were placed in the responsive group. RESULTS: Sixty (88.2%) of 68
eyes were placed in the responsive group and the other 8 eyes (11.8%) were placed
in the refractory group. At the pretreatment examination, fluorescein angiography
showed extensive leakage from occluded vessels in 52 (86.7%) of the 60 eyes in
the responsive group and focal leakages from microaneurysms or dilated
capillaries in the other 8 eyes (13.3%). In the refractory group, 7 (87.5%) of 8
eyes had only focal leakage and 1 eye (12.5%) had extensive leakage (P < 0.0001).
The mean initial subfoveal choroidal thickness in the eyes with branch retinal
vein occlusion in the responsive group was significantly thicker than that in the
fellow eyes (278.0 +/- 90.5 MUm, 249.9 +/- 94.4 MUm; P < 0.0001). On the other
hand, the mean initial subfoveal choroidal thickness in the refractory group was
not significantly different from that of the fellow eyes (P = 0.4002).
CONCLUSION: The dye leakage pattern in the fluorescein angiography images and
choroidal thickness may be associated with response to ranibizumab therapy.
PMID- 28492436
TI - Continuous Regional Anesthesia and Inpatient Rehabilitation for Pediatric Complex
Regional Pain Syndrome.
AB - BACKGROUND: Evidence supports treatment of pediatric complex regional pain
syndromes (CRPS) with physical and occupational therapy and cognitive-behavioral
therapy. Some patients have persistent pain and/or limb dysfunction despite these
treatments. We performed a retrospective study of pediatric patients with CRPS
treated by continuous epidural or peripheral perineural local anesthetic
infusions along with inpatient rehabilitation at Boston Children's Hospital.
METHODS: After approval from the institutional review board, electronic medical
records were reviewed for patients treated between September 2003 and September
2014. Primary outcomes were pain and functional scores. Data were collected at
the first encounter, at follow-up visits between 4 months before and after
admission, and daily while inpatient. Changes over time were assessed using
Wilcoxon tests with Dunn corrections. Clinical significance of benefit or harm
was assessed by the method of Jacobson and Truax. Response predictors were
analyzed using linear mixed models and exploratory logarithmic regression
analyses. RESULTS: Pain, function, and disability scores improved during
hospitalization and in follow-up over a 4-month period. Seventy percent of
patients achieved clinically significant benefit (56% for pain reduction and 40%
increased functionality, respectively). Univariate and adjusted predictors of
favorable outcome included preadmission resting Numeric Pain Rating Scale score
of less than 6 (odds ratio, 5.0; P = 0.0164 and subsequent attendance at the
Pediatric Pain Rehabilitation Center at Boston Children's Hospital (odds ratio,
5.0; P = 0.0206). Mean pain scores greater than 3 during the regional anesthesia
infusion predicted less favorable outcome. CONCLUSIONS: Continuous regional
anesthesia may be an option to facilitate intensive rehabilitation for selected
pediatric patients with CRPS. Further research should help clarify the role of
regional anesthesia in a comprehensive management program.
PMID- 28492437
TI - Continuous Intrathecal Infusion of Cannabinoid Receptor Agonists Attenuates Nerve
Ligation-Induced Pain in Rats.
AB - BACKGROUND AND OBJECTIVES: Cannabinoid receptors (CB1R/CB2R) are known to play
important roles in pain transmission. In this study, we investigated the effects
of continuous intrathecal infusion of CB1/2R agonists in the L5/6 spinal nerve
ligation pain model. METHODS: Under isoflurane anesthesia, rats received nerve
ligation and intrathecal catheter connected to an infusion pump. After surgery,
saline (1 MUL/h), CB1/2R agonist WIN55,212-2, CB1R agonist ACEA, or CB2R agonist
AM1241 (1 MUmol/h) was given intrathecally for 7 days. The mechanical and thermal
sensitivities of rat hindpaw were determined by von Frey hair and radiant heat
tests. The expression of CB1/2R and protein levels of CB1/2R, Iba1, glial
fibrillary acidic protein, and tumor necrosis factor alpha were examined by
immunofluorescence study and Western blotting. RESULTS: On postligation day 7,
rats that received WIN55,212-2, ACEA or AM1241 had significantly higher mean
withdrawal thresholds (6.8, 8.4, and 10.2 g) and latencies (6.3, 7.3, and 9.1
seconds) than did saline-treated rats (1.7 g, 2.2 seconds). Cannabinoid receptors
were expressed not only in IB4 (isolectin B4) and CGRP (calcitonin gene-related
peptide) dorsal root ganglion neurons, their central terminals, and peripheral
axons, but also in neurons, microglia, and astrocytes in spinal cord. Cannabinoid
receptor agonists enhanced nerve ligation-induced up-regulation of cannabinoid
receptor in spinal cord and dorsal root ganglion. Treatment with WIN55,212-2 or
AM1241, but not ACEA, markedly reduced nerve ligation-induced up-regulation of
Iba1, glial fibrillary acidic protein, and tumor necrosis factor alpha in spinal
cord. CONCLUSIONS: Continuous intrathecal infusion of CB1/2R agonists elicits
antinociception in the pain model. The mechanisms might involve their actions on
neurons and glial cells. CB2R, but not CB1R, seems to play an important role in
the regulation of nerve injury-induced neuroinflammation.
PMID- 28492438
TI - Advancing Safety in Intrathecal Analgesia: A Novel Web-Based Pharmacologic
Requisition Platform and Data Repository for Intrathecal Drug Delivery Devices.
PMID- 28492439
TI - Retrobulbar Block in Pediatric Vitreoretinal Surgery Eliminates the Need for
Intraoperative Fentanyl and Postoperative Analgesia: A Randomized Controlled
Study.
AB - BACKGROUND AND OBJECTIVES: Pediatric ophthalmologic surgery is traditionally
accomplished by general anesthesia with opioids, but respiratory depression
remains a major concern. Our study compared the efficacy of retrobulbar block
with systemic fentanyl on pain, hemodynamic, and stress response in pediatric
vitreoretinal surgery. METHODS: A prospective double-blind, randomized controlled
study was performed comparing retrobulbar block with intravenously administered
fentanyl in 28 children aged 1 to 6 years undergoing vitreoretinal surgery. After
general anesthesia was induced, retrobulbar block with 0.5% ropivacaine was
accomplished in group RB (general anesthesia plus retrobulbar block) (n = 13),
and normal saline was injected into retrobulbar space in group F (general
anesthesia alone) (n = 15). Fentanyl 0.5 MUg/kg was administered when signs of
inadequate anesthesia were observed. RESULTS: Respiratory depression (defined as
a persistent respiratory rate <10 breaths/min or persistent oxygen desaturation
<92%) was observed in 5 of 15 patients in group F after laryngeal mask airway was
removed in the operating room, compared with none in group RB. All children in
group F consumed intraoperative fentanyl rescue (average intraoperative fentanyl
consumption, 1.3 +/- 0.3 MUg/kg) compared with none in group RB. Pain scores
assessed with Faces, Legs, Activity, Cry and Consolability were significantly
lower in group RB than in group F (1 [0, 3.5] vs 5 [3, 7], P = 0.003) immediately
after laryngeal mask airway removal. Heart rate in group RB was significantly
lower than that in group F before anesthesia induction, at the beginning and end
of surgery, respectively. Mean blood pressure in group RB was significantly lower
than that in group F at the beginning of surgery. Postoperative tumor necrosis
factor alpha concentration in group RB was significantly lower than that in group
F. CONCLUSIONS: Retrobulbar block is safe and effective as an alternative to
systemic fentanyl and could provide better pain management, hemodynamic
suppression, and stress response suppression in pediatric vitreoretinal surgery.
PMID- 28492440
TI - Diskitis, Osteomyelitis, Spinal Epidural Abscess, Meningitis, and Endocarditis
Following Sacroiliac Joint Injection for the Treatment of Low-Back Pain in a
Patient on Therapy for Hepatitis C Virus.
AB - OBJECTIVE: Sacroiliac joint injections are frequently performed procedures in the
management of acute and chronic low-back pain, including patients with various
immunocompromised states. Infectious complications following these procedures
along with other spinal injections are rarely reported, but the true incidence is
unknown. The purpose of this report is to highlight the devastating neurologic
sequela that can occur, and to discuss potential future management strategies.
CASE REPORT: We present a patient who developed diskitis, osteomyelitis, spinal
epidural abscess, meningitis, and endocarditis from Staphylococcus aureus, all of
which developed shortly after a sacroiliac joint injection. The patient was on
treatment for hepatitis C virus, and the resulting immunocompromised state likely
contributed to the outcome. CONCLUSIONS: Immunocompromised patients should be
identified prior to treatment, and the small possibility of devastating
complications should be thoughtfully weighed against the potential benefit of the
procedure. Conservative management should be maximized initially, and if a
procedure is done, strict asepsis must be maintained. Prophylaxis for S. aureus
should be considered for immunocompromised patients undergoing interventional
spine procedures.
PMID- 28492441
TI - Residual Enoxaparin Activity, Anti-Xa Levels, and Concerns About the American
Society of Regional Anesthesia and Pain Medicine Anticoagulation Guidelines.
AB - Currently, the American Society of Regional Anesthesia and Pain Medicine (ASRA)
anticoagulation guidelines recommend that before the performance of a neuraxial
procedure a minimum of 24 hours should elapse following a treatment dose of
enoxaparin (1 mg/kg twice daily or 1.5 mg/kg once daily). The guidelines have
since their inception also consistently recommended against the routine use of
anti-Xa level monitoring for patients receiving enoxaparin. However, we noted in
our clinical practice that anti-Xa levels were frequently still elevated despite
patients meeting the time-based recommendation for treatment dose enoxaparin. To
further investigate the possibility that residual anticoagulant activity may
persist longer than 24 hours after a treatment dose of enoxaparin, we assessed
anti-Xa level activity in patients presenting for elective surgery. Despite
nearly universal compliance with ASRA's anticoagulation guidelines (1 sample was
drawn at 23.25 hours), anti-Xa activity was found to be elevated in 11 of 19
patients. While 10 patients had an anti-Xa level within the peak prophylactic
range (0.2-0.5 IU/mL), 1 patient's level was found to still be in the peak
therapeutic range (0.5-1.0 IU/mL). These findings suggest that significant
anticoagulant activity may persist longer than previously appreciated after the
last treatment dose of enoxaparin and that the current time-based ASRA
recommendation may not be conservative enough. Further research is needed to
delineate the level of anti-Xa activity below which it is likely safe to proceed
with a neuraxial procedure, but it may be time to reconsider the utility of anti
Xa level monitoring when it is available.
PMID- 28492442
TI - Neuroendovascular Intervention: Evolving at the Intersection of Neurosurgery and
Neuro-Ophthalmology.
PMID- 28492443
TI - Intracranial Displacement of the Eye After Blunt Trauma: Retraction.
PMID- 28492444
TI - Neuro-Ophthalmology: Transitioning From Old to New Models of Health Care
Delivery.
AB - In contradiction to fundamental laws of supply and demand, 2 decades of payment
policies have led to some medical specialties experiencing declines in both
manpower and reimbursement. This paradox has resulted in increasingly long wait
times to see some specialists, some specialties becoming less attractive to
potential trainees, and a dearth of new trainees entering these fields. Evolving
models of health care delivery hold the promise of increasing patient access to
most providers and may diminish costs and improve outcomes for most
patients/conditions. However, patients who need care in understaffed fields may,
in the future, be unable to quickly access a specialist with the requisite
expertise. Impeding the sickest and most complex patients from seeing physicians
with appropriate expertise may lead to increased costs and deleterious outcomes
consequences contrary to the goals of health care reform. To ensure appropriate
access for these patients requires 2 conditions: 1. Compensation models that do
not discourage trainees from pursuing nonprocedural specialties, and 2. A care
delivery model that expediently identifies and routes these patients to the
appropriate specialist.
PMID- 28492445
TI - Clomiphene Citrate Associated With Palinopsia.
PMID- 28492446
TI - Five Community-wide Approaches to Physical Activity Promotion: A Cluster Analysis
of These Activities in Local Health Jurisdictions in 6 States.
AB - OBJECTIVE: Local health departments (LHDs) have essential roles to play in
ensuring the promotion of physical activity (PA) in their communities in order to
reduce obesity. Little research exists, however, regarding the existence of these
PA interventions across communities and how these interventions may impact
community health. DESIGN: In this exploratory study, we used cluster analysis to
identify the structure of co-occurring PA interventions, followed by regression
analysis to quantify the association between the patterns of PA interventions and
prevalence of PA and obesity at a population level. SETTING: Our study setting
included local health jurisdictions in Colorado, Florida, Minnesota, New Jersey,
Tennessee, and Washington. PARTICIPANTS: Participating jurisdictions were those
218 local health jurisdictions (mostly counties) from which LHD leaders had
provided data in 2013 for the Multi-Network Practice and Outcome Variation
Examination Study. MAIN OUTCOME MEASURES: We obtained unique public health
activities data on PA interventions conducted in 2012 from 218 LHDs in 6
participating states. We categorized jurisdictions using cluster analysis, based
on PA intervention approaches indicated by LHD leaders as available in their
communities and then examined associations between categories and prevalence of
obesity and of residents engaged in PA. RESULTS: We identified 5 distinct PA
intervention categories representing community-wide approaches-Comprehensive
Approach, Built Environment, Personal Health, School-Based Interventions, and No
Apparent Activities. Prevalence rates of obesity and PA among jurisdictions in
the intervention clusters were significantly different from jurisdictions with No
Apparent Activities, with more population-level approaches most significantly
related to beneficial outcomes. CONCLUSION: Our findings suggest the importance
of standardized public health services data for generating evidence regarding
health-related outcomes. The intervention categories we identified appear to
reflect broad, local community-wide prevention approaches and demonstrated that
population-level PA interventions can be testable and may have particularly
beneficial relationships to community health. Widespread adoption of such
standardized data depicting local public health prevention activity could support
monitoring practice change, performance improvement, comparisons across
communities that could reduce unnecessary variation, and the generation of
evidence for public health practice and policy-making.
PMID- 28492447
TI - The Yellow Fever Vaccine Misadventure of 1942.
AB - In 1942, a hepatitis B outbreak occurred in the US Army after vaccination with
contaminated lots of 17D yellow fever vaccine; long-term sequelae were
surprisingly limited, and retrospective studies of carrier rates, cirrhosis, and
hepatocellular carcinoma were found to be minimal. Later studies identified the
contaminant as hepatitis B virus (HBV) in the human serum component of the
vaccine. Other than 2 follow-up studies of long-term sequelae and reports within
US Military archives, the event has never been fully elucidated in its proper
historical context in the medical literature available through MEDLINE (PubMed).
The outbreak resulted in nearly 50 000 clinical cases, including 29 000 cases of
overt jaundice. More than 300 000 troops may have been infected with HBV. The
decision to immunize troops received criticism, but the decision may have been
reasonable, given the exigencies of an impending war and the possibility that
yellow fever could spread to future theaters of war. The epidemic was the largest
and most well-documented vaccine-related epidemic in history. Today, independent
of war, globalization has actually increased the likelihood of yellow fever
importations to vulnerable areas of the world.
PMID- 28492448
TI - Drivers and Barriers for Adopting Accreditation at Local Health Departments for
Their Performance Improvement Effort.
AB - CONTEXT: A national system of voluntary public health accreditation for state,
local, and tribal health departments (local health departments [LHDs]) is part of
a movement that aims to improve public health performance with ultimate impact on
population health outcomes. Indiana is a good setting for the study of LHD
accreditation adoption because several LHDs reported de-adopting accreditation in
a recent statewide survey and because 71% of Indiana counties serve populations
of 50 000 or less. DESIGN: A systematic method of analyzing qualitative data
based on the Performance Improvement Model framework to expand our understanding
of de-adoption of public health accreditation. SETTING/PARTICIPANTS: In 2015, we
conducted a key informant interview study of the 3 LHDs that decided to delay
their engagement in the accreditation based on findings from an Indiana survey on
LHD accreditation adoption. The study is an exploration of LHD accreditation de
adoption and of the contributions made to its understanding by the Performance
Improvement Model. RESULT: The study found that top management team members are
those who champion accreditation adoption, and that organizational structure and
culture facilitate the staff's embracing of the change. The Performance
Improvement Model was found to enhance the elucidation of the inner domain
elements of Consolidated Framework for Implementation Research in the context of
de-adoption of public health accreditation. CONCLUSION: Governing entities'
policies and priorities appear to mediate whether the LHDs are able to continue
accreditation pursuit. Lacking any of these driving forces appears to be
associated with decisions to de-adoption of accreditation. Further work is
necessary to discern specific elements mediating decisions to pursue
accreditation. This study demonstrates the added knowledge of Performance
Improvement Model (PIM) to the CFIR framework. A large scale study is called to
further clarify and discern supports of specific to the needs of individual LHDs
for their performance improvement effort.
PMID- 28492450
TI - The Potential Role for Health Impact Assessments in Nonprofit Hospital Community
Benefit Activities.
PMID- 28492451
TI - Program-Led Program-Science: The Public Health Impact of the CDC Category C
Health Department Model for HIV Prevention.
PMID- 28492449
TI - Measuring Subcounty Differences in Population Health Using Hospital and Census
Derived Data Sets: The Missouri ZIP Health Rankings Project.
AB - CONTEXT: Measures of population health at the subcounty level are needed to
identify areas for focused interventions and to support local health improvement
activities. OBJECTIVE: To extend the County Health Rankings population health
measurement model to the ZIP code level using widely available hospital and
census-derived data sources. DESIGN: Retrospective administrative data study.
SETTING: Missouri. POPULATION: Missouri FY 2012-2014 hospital inpatient,
outpatient, and emergency department discharge encounters (N = 36 176 377) and
2015 Nielsen data. MAIN OUTCOME MEASURES: ZIP code-level health factors and
health outcomes indices. RESULTS: Statistically significant measures of
association were observed between the ZIP code-level population health indices
and published County Health Rankings indices. Variation within counties was
observed in both urban and rural areas. Substantial variation of the derived
measures was observed at the ZIP code level with 20 (17.4%) Missouri counties
having ZIP codes in both the top and bottom quintiles of health factors and
health outcomes. Thirty of the 46 (65.2%) counties in the top 2 county quintiles
had ZIP codes in the bottom 2 quintiles. CONCLUSIONS: This proof-of-concept
analysis suggests that readily available hospital and census-derived data can be
used to create measures of population health at the subcounty level. These widely
available data sources could be used to identify areas of potential need within
counties, engage community stakeholders, and target interventions.
PMID- 28492453
TI - Late Life.
PMID- 28492452
TI - The Changing Landscape of HIV Prevention in the United States: Health Department
Experiences and Local Adaptations in Response to the National HIV/AIDS Strategy
and High-Impact Prevention Approach.
AB - OBJECTIVE: HIV prevention has changed substantially in recent years due to
changes in national priorities, biomedical advances, and health care reform.
Starting in 2010, motivated by the National HIV/AIDS Strategy (NHAS) and the
Centers for Disease Control and Prevention's (CDC's) High-Impact Prevention
(HIP), health departments realigned resources so that cost-effective, evidence
based interventions were targeted to groups at risk in areas most affected by
HIV. This analysis describes how health departments in diverse settings were
affected by NHAS and HIP. METHODS: We conducted interviews and a consultation
with health departments from 16 jurisdictions and interviewed CDC project
officers who monitored programs in 5 of the jurisdictions. Participants were
asked to describe changes since NHAS and HIP and how they adapted. We used
inductive qualitative analysis to identify themes of change. RESULTS: Health
departments improved their HIV prevention practices in different ways. They
aligned jurisdictional plans with NHAS and HIP goals, increased local data use to
monitor program performance, streamlined services, and strengthened partnerships
to increase service delivery to persons at highest risk for
infection/transmission. They shifted efforts to focus more on the needs of people
with diagnosed HIV infection, increased HIV testing and routine HIV screening in
clinical settings, raised provider and community awareness about preexposure
prophylaxis, and used nontraditional strategies to successfully engage out-of
care people with diagnosed HIV infection. However, staff-, provider-, and data
related barriers that could slow scale-up of priority programs were consistently
reported by participants, potentially impeding the ability to meet national
goals. CONCLUSION: Findings suggest progress toward NHAS and HIP goals has been
made in some jurisdictions but highlight the need to monitor prevention programs
in different contexts to identify areas for improvement and increase the
likelihood of national success. Health departments and federal funders alike can
benefit from the routine sharing of successes and challenges associated with
local policy implementation, considering effects on the overall portfolio of
programs.
PMID- 28492454
TI - Use of Lithium in Severe Acute Manic Episodes: Retrospective Prescription
Practice From a Tertiary Inpatient Unit.
AB - OBJECTIVE: A retrospective chart review was performed to investigate the common
preferences of clinicians for the pharmacological treatment of acute manic
episodes, with particular regard to lithium use, and to assess the adherence of
clinical practice to established guidelines. METHODS: Cases of manic episodes in
patients admitted to Bakirkoy Mazhar Osman Mental Health and Neurological
Diseases Education and Research Hospital were retrospectively reviewed. Length of
stay, medication data, serum levels, and adverse effects were evaluated for
patients who received lithium therapy (N=98). RESULTS: On the first day of
lithium treatment, 81 patients received 900 to 1200 mg of lithium. In total, 44
patients were discharged with the same dose as that given on the first day of
treatment. With the exception of 1 patient, the dose was increased by 300 to 600
mg in the remaining patients within the first 10 days on the basis of serum drug
concentrations. The mean serum concentrations of lithium in the first week were
0.67+/-0.17 mEq/L in patients with no dose increase, and 0.51+/-0.15 mEq/L in
patients who did receive a dose increase. In total, 94 patients received at least
1 antipsychotic medication in addition to lithium. CONCLUSIONS: Clinicians
attempted to maintain serum lithium levels above 0.60 mEq/L at the time of acute
treatment initiation, consistent with established guidelines. Clinical practice
in large inpatient settings may force clinicians to use lithium in combination
with antipsychotics for the treatment of acute mania; the delayed action of
lithium and the need for rapid stabilization may drive these practices.
PMID- 28492455
TI - Reevaluating Antidepressant Selection in Patients With Bruxism and
Temporomandibular Joint Disorder.
AB - Temporomandibular joint disorder (TMD) is a broad pain disorder that refers to
several conditions affecting the temporomandibular joint of the jaw and the
muscles of mastication. As with most pain disorders, a high prevalence of
depression and anxiety is associated with TMD. Research has shown that selective
serotonin reuptake inhibitors (SSRIs), the first-line drug therapy for major
depressive disorder, may not be suitable for TMD patients because SSRIs can
induce teeth-grinding, otherwise known as bruxism. This is problematic because
bruxism is believed to further exacerbate TMD. Therefore, the purpose of this
literature review is to better understand the mechanism of SSRI-induced bruxism,
as well as discuss alternative antidepressant options for treating depression and
anxiety in patients with bruxism and TMD. Alternative classes of antidepressants
reviewed include serotonin-norepinephrine reuptake inhibitors, tricyclic
antidepressants, atypical antidepressants, and monoamine oxidase inhibitors.
Findings indicate that dopamine agonists and buspirone are currently the most
effective medications to treat the side effects of SSRI-induced bruxism, but
results regarding the effectiveness of specific antidepressants that avoid
bruxism altogether remain inconclusive.
PMID- 28492456
TI - Calmer Life: A Hybrid Effectiveness-implementation Trial for Late-life Anxiety
Conducted in Low-income, Mental Health-Underserved Communities.
AB - OBJECTIVE: Anxiety is common among older adults and is associated with multiple
negative outcomes. Late-life anxiety is usually unrecognized by providers and
undertreated, although evidence supports the effectiveness of psychosocial
treatment. Access to mental health care is especially poor among African American
seniors. New treatment models are needed to expand the reach of mental health
care to minority elders. METHODS: Our article outlines a study designed to test
the effectiveness and implementation potential of Calmer Life (CL), a community
based, person-centered, flexible and culturally tailored intervention for late
life anxiety and worry, offered in low-income, mental health-underserved and
predominantly African American communities. CL is skills-based, but also includes
resource counseling and an option to integrate religion/spirituality. The study
population includes individuals 50 years of age and older who are experiencing
high levels of worry. The program was developed in the context of a community
academic partnership with organizations that provide services for seniors in
underserved communities, and it trains nontraditional community providers to
deliver the intervention. RESULTS: Study progress to date, challenges, and
lessons learned are discussed. Data collection is ongoing, and study findings
will be available in late 2017. CONCLUSIONS: CL will offer valuable information
to help expand the reach of anxiety treatment among minority seniors living in
underserved neighborhoods.
PMID- 28492457
TI - The Role of Amantadine Withdrawal in 3 Cases of Treatment-Refractory Altered
Mental Status.
AB - Amantadine, which was originally developed as an antiviral medication, functions
as a dopamine agonist in the central nervous system and consequently is utilized
in the treatment of Parkinson disease, drug-induced extrapyramidal reactions, and
neuroleptic malignant syndrome. For reasons that are not entirely understood,
abrupt changes in amantadine dosage can produce a severe withdrawal syndrome.
Existing medical literature describes case reports of amantadine withdrawal
leading to delirium, which at times has progressed to neuroleptic malignant
syndrome. Amantadine withdrawal may be under-recognized by mental health
clinicians, which has the potential to lead to protracted hospital courses and
suboptimal outcomes. The goal of this case series is to highlight the role of
amantadine withdrawal in the cases of 3 medically complex patients with altered
mental status. In the first case, the cognitive side effects of electroconvulsive
therapy masked acute amantadine withdrawal in a 64-year-old man with Parkinson
disease. In the second case, a 75-year-old depressed patient developed a
catatonic delirium when amantadine was discontinued. Finally, a refractory case
of neuroleptic malignant syndrome in a 57-year-old patient with schizoaffective
disorder rapidly resolved with the reintroduction of outpatient amantadine. These
cases highlight several learning objectives regarding amantadine withdrawal
syndrome: First, it may be concealed by co-occurring causes of delirium in
medically complex patients. Second, its symptoms are likely to be related to a
cortical and limbic dopamine shortage, which may be reversed with
electroconvulsive therapy or reintroduction of amantadine. Third, its clinical
presentation may occur on a spectrum and may include features suggestive of
delirium, catatonia, or neuroleptic malignant syndrome.
PMID- 28492458
TI - Switching From the Oral to the Depot Formulation of a Medication: Clinically
Relevant Pharmacokinetic Concepts and Considerations.
AB - This column presents principles that will aid the prescriber in transitioning
patients from an oral to a depot antipsychotic medication. The column covers the
differences in the pharmacokinetics of oral versus depot formulations that are
critical in making a smooth transition. Also discussed are some of the reasons to
use these medications, which, in the author's opinion, are currently
underutilized. This column focuses on the big picture and the fundamentals of
oral versus depot formulations rather than comparing the relative merits or
potential advantages of the various marketed depot formulations.
PMID- 28492459
TI - Making Psychotherapy Great Again?
AB - Psychotherapy never stopped being as "great" as other treatments. This column
explores the evidence base for both psychotherapy and medications, using
depression as a specific example. The limitations are comparable for
psychotherapy and medication, with much of the evidence based on small degrees of
"statistically significant" rather than "clinically meaningful" change. Our
field's biomedical emphasis leads to a false assumption that most patients
present with single disorders, when comorbidity is the rule rather than the
exception. This false assumption contributes to limitations in the evidence base
and in our ability to treat patients optimally.
PMID- 28492460
TI - Performance Validity Testing in Neuropsychology: Methods for Measurement
Development and Maximizing Diagnostic Accuracy.
AB - In the first column in this 2-part series, Performance Validity Testing in
Neuropsychology: Scientific Basis and Clinical Application-A Brief Review, the
authors introduced performance validity tests (PVTs) and their function, provided
a justification for why they are necessary, traced their ongoing endorsement by
neuropsychological organizations, and described how they are used and interpreted
by ever increasing numbers of clinical neuropsychologists. To enhance readers'
understanding of these measures, this second column briefly describes common
detection strategies used in PVTs as well as the typical methods used to validate
new PVTs and determine cut scores for valid/invalid determinations. We provide a
discussion of the latest research demonstrating how neuropsychologists can
combine multiple PVTs in a single battery to improve sensitivity/specificity to
invalid responding. Finally, we discuss future directions for the research and
application of PVTs.
PMID- 28492461
TI - Overcoming Barriers to Initiating Medication-assisted Treatment for Heroin Use
Disorder in a General Medical Hospital: A Case Report and Narrative Literature
Review.
AB - Deaths due to heroin overdoses are increasing and are the leading cause of death
among intravenous heroin users. Although medication-assisted treatment (MAT)
improves morbidity and mortality in patients with opioid use disorders, it is
underutilized. Most efforts to expand access to MAT have focused on outpatient
settings. Although the inpatient medical setting presents a critical opportunity
to initiate treatment, general hospitals are often unfamiliar with MAT, creating
a number of barriers to its use. In this report, we describe the case of a woman
with heroin use disorder who was initiated on buprenorphine maintenance treatment
while hospitalized for cardiac disease related to her intravenous heroin use.
Barriers to initiating buprenorphine in this case included patient, practitioner,
and organizational factors, and, ultimately, shared misperceptions about the
feasibility of administering buprenorphine in a general medical hospital. These
barriers were addressed, buprenorphine was initiated, and the patient
demonstrated reduced craving, improved postoperative pain control, improved
overall well-being, increased engagement in discharge planning, and acceptance of
referral for addiction specialty aftercare. Our experience with this patient
suggests that it is feasible to initiate buprenorphine in acute medical settings
and that such treatment can improve patient outcomes. Our review of the
literature reveals emerging evidence supporting the value of this practice.
PMID- 28492462
TI - Synthetic Cannabinoids Use in Elderly Patients.
AB - Synthetic cannabinoids are becoming a public health concern. No data are
apparently available concerning use of synthetic cannabinoids in the elderly. We
report two cases of elderly individuals who used synthetic cannabinoids and were
admitted to a psychiatric hospital.
PMID- 28492463
TI - Impact of an Alcohol Withdrawal Treatment Pathway on Hospital Length of Stay: A
Retrospective Observational Study Comparing Pre and Post Pathway Implementation.
AB - OBJECTIVE: To determine if the implementation of a hospital-specific alcohol
withdrawal treatment pathway used in a medical-surgical patient population
decreased hospital length of stay (LOS) compared with the standard of care.
METHODS: This retrospective observational study, conducted in a large academic
tertiary care hospital, involved 582 subjects who met criteria for study
inclusion, with 275 subjects in the 2010 cohort and 307 in the 2012 cohort. The
Alcohol Withdrawal Project Team was formed with the goal of creating a
standardized approach to the recognition and treatment of alcohol withdrawal at
Duke University Hospital. The group created a computerized physician order entry
alcohol withdrawal treatment pathway with 4 possible treatment paths chosen on
the basis of current withdrawal symptoms, vital signs, and alcohol withdrawal
history. The 4 treatment paths are 1 prophylaxis; 2 mild-to-moderate withdrawal;
3 moderate-to-severe withdrawal, and 4 severe withdrawal/alcohol withdrawal
delirium. Each treatment path corresponds to a different lorazepam dose and dose
schedule and symptom assessment. This pathway was implemented in the hospital at
the end of 2011. RESULTS: Using a Cox proportional hazards model and adjusting
for covariates, there was a 1 day [95% confidence interval (CI), 1-2 d] reduction
in median hospital LOS between the 2010 and 2012 cohorts, 5 versus 4 days,
respectively. The average ratio in hospital LOS between the 2 cohorts was 1.25
(95% CI, 1.25-1.67). The CI was estimated by bootstrapping and indicated a
significantly longer LOS in the 2010 cohort compared with the 2012 cohort.
Nonsignificant changes were found in the proportion of subjects admitted to the
intensive care unit (24% in 2010 vs. 29.3% in 2012), LOS in the intensive care
unit (7.1+/-8 d in 2010 vs. 5.6+/-6.9 d in 2012), and proportion of patients
discharged with a diagnosis of delirium tremens (17.8% in 2010 vs. 15.3% in
2012). CONCLUSIONS: This study demonstrates the successful implementation of an
alcohol withdrawal treatment pathway in a medical-surgical population
hospitalized in a large tertiary care facility with significant impact on
hospital LOS.
PMID- 28492464
TI - Validity of Forced Eyelid Closure Test: A Novel Clinical Screening Test for
Ocular Myasthenia Gravis.
AB - BACKGROUND: Forced eyelid closure test (FECT) is a clinical screening test
developed from the original Cogan lid twitch (CLT) sign to assist in the
diagnosis of ocular myasthenia gravis (OMG), We evaluated the sensitivity and
specificity of FECT compared with CLT and benchmarked to standard diagnostic
tests. METHODS: This study was a retrospective chart review of 48 patients using
electronic medical records of those that presented with ptosis and/or diplopia at
Doheny Eye Institute, University of California, Los Angeles between February 2015
and April 2016. Patients without FECT testing were excluded. FECT and CLT
results, and final diagnosis were recorded. To perform FECT, the patient was
asked to squeeze his or her eyelids shut for 5-10 seconds then open quickly and
fixate in primary position. The excessive upward overshoot of eyelids movement
indicated a positive FECT. The test was performed by a neuro-ophthalmologist
before establishing the diagnosis. Patients who had equivocal test results and/or
inconclusive final diagnosis were excluded. RESULTS: Of the 48 patients studied,
18 patients (37.5%) had positive FECT; 15 of whom had a final diagnosis of OMG
(83.3%). Of the 30 patients with negative FECT, 1 had OMG (3.3%). Of the 48
patients, 35 patients also had a documented CLT result (72.9%). CLT was positive
in 11 of these 35 patients (31.4%), and 9 of these 11 had OMG (81.8%). Of the 24
patients with negative CLT, 2 of them had OMG (8.3%). Sensitivity and specificity
of FECT were 94% and 91% (joint 95% confidence region: sensitivity * specificity
= [0.70, 1] * [0.75, 1]). The relative true-positive fraction (rTPF) between FECT
and CLT was 1.15; the relative false-positive fraction was 1.31. CONCLUSIONS:
FECT is a simple clinical screening test with good sensitivity and specificity
for OMG.
PMID- 28492465
TI - Mitigation of Patulin in Fresh and Processed Foods and Beverages.
AB - Patulin is a mycotoxin of food safety concern. It is produced by numerous species
of fungi growing on fruits and vegetables. Exposure to the toxin is connected to
issues neurological, immunological, and gastrointestinal in nature. Regulatory
agencies worldwide have established maximum allowable levels of 50 ug/kg in
foods. Despite regulations, surveys continue to find patulin in commercial food
and beverage products, in some cases, to exceed the maximum limits. Patulin
content in food can be mitigated throughout the food processing chain. Proper
handling, storage, and transportation of food can limit fungal growth and patulin
production. Common processing techniques including pasteurisation, filtration,
and fermentation all have an effect on patulin content in food but individually
are not sufficient safety measures. Novel methods to remove or detoxify patulin
have been reviewed. Non-thermal processing techniques such as high hydrostatic
pressure, UV radiation, enzymatic degradation, binding to microorganisms, and
chemical degradation all have potential but have not been optimised. Until
further refinement of these methods, the hurdle approach to processing should be
used where food safety is concerned. Future development should focus on
determining the nature and safety of chemicals produced from the breakdown of
patulin in treatment techniques.
PMID- 28492467
TI - A Study of Pattern Prediction in the Monitoring Data of Earthen Ruins with the
Internet of Things.
AB - An understanding of the changes of the rammed earth temperature of earthen ruins
is important for protection of such ruins. To predict the rammed earth
temperature pattern using the air temperature pattern of the monitoring data of
earthen ruins, a pattern prediction method based on interesting pattern mining
and correlation, called PPER, is proposed in this paper. PPER first finds the
interesting patterns in the air temperature sequence and the rammed earth
temperature sequence. To reduce the processing time, two pruning rules and a new
data structure based on an R-tree are also proposed. Correlation rules between
the air temperature patterns and the rammed earth temperature patterns are then
mined. The correlation rules are merged into predictive rules for the rammed
earth temperature pattern. Experiments were conducted to show the accuracy of the
presented method and the power of the pruning rules. Moreover, the Ming Dynasty
Great Wall dataset was used to examine the algorithm, and six predictive rules
from the air temperature to rammed earth temperature based on the interesting
patterns were obtained, with the average hit rate reaching 89.8%. The PPER and
predictive rules will be useful for rammed earth temperature prediction in
protection of earthen ruins.
PMID- 28492468
TI - Radon Mitigation Approach in a Laboratory Measurement Room.
AB - Radon gas is the second leading cause of lung cancer, causing thousands of deaths
annually. It can be a problem for people or animals in houses, workplaces,
schools or any building. Therefore, its mitigation has become essential to avoid
health problems and to prevent radon from interfering in radioactive
measurements. This study describes the implementation of radon mitigation systems
at a radioactivity laboratory in order to reduce interferences in the different
works carried out. A large set of radon concentration samples is obtained from
measurements at the laboratory. While several mitigation methods were taken into
account, the final applied solution is explained in detail, obtaining thus very
good results by reducing the radon concentration by 76%.
PMID- 28492469
TI - A Blade Tip Timing Method Based on a Microwave Sensor.
AB - Blade tip timing is an effective method for blade vibration measurements in
turbomachinery. This method is increasing in popularity because it is non
intrusive and has several advantages over the conventional strain gauge method.
Different kinds of sensors have been developed for blade tip timing, including
optical, eddy current and capacitance sensors. However, these sensors are
unsuitable in environments with contaminants or high temperatures. Microwave
sensors offer a promising potential solution to overcome these limitations. In
this article, a microwave sensor-based blade tip timing measurement system is
proposed. A patch antenna probe is used to transmit and receive the microwave
signals. The signal model and process method is analyzed. Zero intermediate
frequency structure is employed to maintain timing accuracy and dynamic
performance, and the received signal can also be used to measure tip clearance.
The timing method uses the rising and falling edges of the signal and an auto
gain control circuit to reduce the effect of tip clearance change. To validate
the accuracy of the system, it is compared experimentally with a fiber optic tip
timing system. The results show that the microwave tip timing system achieves
good accuracy.
PMID- 28492470
TI - Improvement of Polylactide Properties through Cellulose Nanocrystals Embedded in
Poly(Vinyl Alcohol) Electrospun Nanofibers.
AB - Electrospun nanofibers of poly (vinyl alcohol) (PV) were obtained to improve
dispersion of cellulose nanocrystals (CNC) within hydrophobic biopolymeric
matrices, such as poly(lactic acid) (PLA). Electrospun nanofibers (PV/CNC)n were
successfully obtained with a final concentration of 23% (w/w) of CNC.
Morphological, structural and thermal properties of developed CNC and electrospun
nanofibers were characterized. X-ray diffraction and thermal analysis revealed
that the crystallinity of PV was reduced by the electrospinning process, and the
incorporation of CNC increased the thermal stability of biodegradable nanofibers.
Interactions between CNC and PV polymer also enhanced the thermal stability of
CNC and improved the dispersion of CNC within the PLA matrix. PLA materials with
CNC lyophilized were also casted in order to compare the properties with
materials based on CNC containing nanofibers. Nanofibers and CNC were
incorporated into PLA at three concentrations: 0.5%, 1% and 3% (CNC respect to
polymer weight) and nanocomposites were fully characterized. Overall, nanofibers
containing CNC positively modified the physical properties of PLA materials, such
as the crystallinity degree of PLA which was greatly enhanced. Specifically,
materials with 1% nanofiber 1PLA(PV/CNC)n presented highest improvements related
to mechanical and barrier properties; elongation at break was enhanced almost
four times and the permeation of oxygen was reduced by approximately 30%.
PMID- 28492471
TI - Autonomous Sensors for Measuring Continuously the Moisture and Salinity of a
Porous Medium.
AB - The article describes a new field sensor to monitor continuously in situ moisture
and salinity of a porous medium via measurements of its dielectric permittivity,
conductivity and temperature. It intends to overcome difficulties and biases
encountered with sensors based on the same sensitivity principle. Permittivity
and conductivity are determined simultaneously by a self-balanced bridge, which
measures directly the admittance of sensor electrodes in medium. All electric
biases are reduced and their residuals taken into account by a physical model of
the instrument, calibrated against reference fluids. Geometry electrode is
optimized to obtain a well representative sample of the medium. The sensor also
permits acquiring a large amount of data at high frequency (six points every
hour, and even more) and to access it rapidly, even in real time, owing to
autonomy capabilities and wireless communication. Ongoing developments intend to
simplify and standardize present sensors. Results of field trials of prototypes
in different environments are presented.
PMID- 28492466
TI - NGF and Its Receptors in the Regulation of Inflammatory Response.
AB - There is growing interest in the complex relationship between the nervous and
immune systems and how its alteration can affect homeostasis and result in the
development of inflammatory diseases. A key mediator in cross-talk between the
two systems is nerve growth factor (NGF), which can influence both neuronal cell
function and immune cell activity. The up-regulation of NGF described in inflamed
tissues of many diseases can regulate innervation and neuronal activity of
peripheral neurons, inducing the release of immune-active neuropeptides and
neurotransmitters, but can also directly influence innate and adaptive immune
responses. Expression of the NGF receptors tropomyosin receptor kinase A (TrkA)
and p75 neurotrophin receptor (p75NTR) is dynamically regulated in immune cells,
suggesting a varying requirement for NGF depending on their state of
differentiation and functional activity. NGF has a variety of effects that can be
either pro-inflammatory or anti-inflammatory. This apparent contradiction can be
explained by considering NGF as part of an endogenous mechanism that, while
activating immune responses, also activates pathways necessary to dampen the
inflammatory response and limit tissue damage. Decreases in TrkA expression, such
as that recently demonstrated in immune cells of arthritis patients, might
prevent the activation by NGF of regulatory feed-back mechanisms, thus
contributing to the development and maintenance of chronic inflammation.
PMID- 28492472
TI - Molecular Surveillance of Cronobacter spp. Isolated from a Wide Variety of Foods
from 44 Different Countries by Sequence Typing of 16S rRNA, rpoB and O-Antigen
Genes.
AB - Cronobacter spp. are emerging infectious bacteria that can cause acute meningitis
and necrotizing enterocolitis in neonatal and immunocompromised individuals.
Although this opportunistic human-pathogenic microorganism has been isolated from
a wide variety of food and environmental samples, it has been primarily linked to
foodborne outbreaks associated with powdered infant formula. The U.S. Food and
Drug Administration use the presence of these microbes as one of the criteria to
assess food adulteration and to implement regulatory actions. In this study, we
have examined 195 aliquots of enrichments from the nine major categories of foods
(including baby and medical food, dairy products, dried food, frozen food, pet
food, produce, ready-to-eat snacks, seafood, and spices) from 44 countries using
conventional microbiological and molecular techniques. The typical colonies of
Cronobacter were then identified by VITEK2 and real-time PCR. Subsequently,
sequence typing was performed on the 51 recovered Cronobacter isolates at the 16S
rRNA, rpoB and seven O-antigen loci for species identification in order to
accomplish an effective surveillance program for the control and prevention of
foodborne illnesses.
PMID- 28492473
TI - Acquisition and Neural Network Prediction of 3D Deformable Object Shape Using a
Kinect and a Force-Torque Sensor.
AB - The realistic representation of deformations is still an active area of research,
especially for deformable objects whose behavior cannot be simply described in
terms of elasticity parameters. This paper proposes a data-driven neural-network
based approach for capturing implicitly and predicting the deformations of an
object subject to external forces. Visual data, in the form of 3D point clouds
gathered by a Kinect sensor, is collected over an object while forces are exerted
by means of the probing tip of a force-torque sensor. A novel approach based on
neural gas fitting is proposed to describe the particularities of a deformation
over the selectively simplified 3D surface of the object, without requiring
knowledge of the object material. An alignment procedure, a distance-based
clustering, and inspiration from stratified sampling support this process. The
resulting representation is denser in the region of the deformation (an average
of 96.6% perceptual similarity with the collected data in the deformed area),
while still preserving the object's overall shape (86% similarity over the entire
surface) and only using on average of 40% of the number of vertices in the mesh.
A series of feedforward neural networks is then trained to predict the mapping
between the force parameters characterizing the interaction with the object and
the change in the object shape, as captured by the fitted neural gas nodes. This
series of networks allows for the prediction of the deformation of an object when
subject to unknown interactions.
PMID- 28492474
TI - Fabrication of Silicon Nanobelts and Nanopillars by Soft Lithography for
Hydrophobic and Hydrophilic Photonic Surfaces.
AB - Soft lithography allows for the simple and low-cost fabrication of nanopatterns
with different shapes and sizes over large areas. However, the resolution and the
aspect ratio of the nanostructures fabricated by soft lithography are limited by
the depth and the physical properties of the stamp. In this work, silicon
nanobelts and nanostructures were achieved by combining soft nanolithography
patterning with optimized reactive ion etching (RIE) in silicon. Using
polymethylmethacrylate (PMMA) nanopatterned layers with thicknesses ranging
between 14 and 50 nm, we obtained silicon nanobelts in areas of square
centimeters with aspect ratios up to ~1.6 and linewidths of 225 nm. The soft
lithographic process was assisted by a thin film of SiOx (less than 15 nm) used
as a hard mask and RIE. This simple patterning method was also used to fabricate
2D nanostructures (nanopillars) with aspect ratios of ~2.7 and diameters of ~200
nm. We demonstrate that large areas patterned with silicon nanobelts exhibit a
high reflectivity peak in the ultraviolet C (UVC) spectral region (280 nm) where
some aminoacids and peptides have a strong absorption. We also demonstrated how
to tailor the aspect ratio and the wettability of these photonic surfaces
(contact angles ranging from 8.1 to 96.2 degrees ) by changing the RIE power
applied during the fabrication process.
PMID- 28492475
TI - Ambiguity Resolution for Phase-Based 3-D Source Localization under Fixed Uniform
Circular Array.
AB - Under fixed uniform circular array (UCA), 3-D parameter estimation of a source
whose half-wavelength is smaller than the array aperture would suffer from a
serious phase ambiguity problem, which also appears in a recently proposed phase
based algorithm. In this paper, by using the centro-symmetry of UCA with an even
number of sensors, the source's angles and range can be decoupled and a novel
algorithm named subarray grouping and ambiguity searching (SGAS) is addressed to
resolve angle ambiguity. In the SGAS algorithm, each subarray formed by two
couples of centro-symmetry sensors can obtain a batch of results under different
ambiguities, and by searching the nearest value among subarrays, which is always
corresponding to correct ambiguity, rough angle estimation with no ambiguity is
realized. Then, the unambiguous angles are employed to resolve phase ambiguity in
a phase-based 3-D parameter estimation algorithm, and the source's range, as well
as more precise angles, can be achieved. Moreover, to improve the practical
performance of SGAS, the optimal structure of subarrays and subarray selection
criteria are further investigated. Simulation results demonstrate the satisfying
performance of the proposed method in 3-D source localization.
PMID- 28492476
TI - A Case Study of Improving Yield Prediction and Sulfur Deficiency Detection Using
Optical Sensors and Relationship of Historical Potato Yield with Weather Data in
Maine.
AB - In Maine, potato yield is consistent, 38 t.ha-1, for last 10 years except 2016
(44 t.ha-1) which confirms that increasing the yield and quality of potatoes with
current fertilization practices is difficult; hence, new or improvised agronomic
methods are needed to meet with producers and industry requirements. Normalized
difference vegetative index (NDVI) sensors have shown promise in regulating N as
an in season application; however, using late N may stretch out the maturation
stage. The purpose of the research was to test Trimble GreenSeeker(r) (TGS) and
Holland Scientific Crop CircleTM ACS-430 (HCCACS-430) wavebands to predict potato
yield, before the second hilling (6-8 leaf stage). Ammonium sulfate, S containing
N fertilizer, is not advised to be applied on acidic soils but accounts for 60
70% fertilizer in Maine's acidic soils; therefore, sensors are used on sulfur
deficient site to produce sensor-bound S application guidelines before
recommending non-S-bearing N sources. Two study sites investigated for this
research include an S deficient site and a regular spot with two kinds of soils.
Six N treatments, with both calcium ammonium nitrate and ammonium nitrate, under
a randomized complete block design with four replications, were applied at
planting. NDVI readings from both sensors were obtained at V8 leaf stages (8 leaf
per plant) before the second hilling. Both sensors predict N and S deficiencies
with a strong interaction with an average coefficient of correlation (r2) ~45.
However, HCCACS-430 was observed to be more virtuous than TGS. The correlation
between NDVI (from both sensors) and the potato yield improved using proprietor
proxy leaf area index (PPLAI) from HCCACS-430, e.g., r2 value of TGS at Easton
site improve from 48 to 60. Weather data affected marketable potato yield (MPY)
significantly from south to north in Maine, especially precipitation variations
that could be employed in the N recommendations at planting and in season
application. This case study addresses a substantial need to revise potato N
recommendations at planting and develop possible in season N recommendation using
ground based active optical (GBAO) sensors.
PMID- 28492477
TI - Measuring Tree Properties and Responses Using Low-Cost Accelerometers.
AB - Trees play a crucial role in the water, carbon and nitrogen cycle on local,
regional and global scales. Understanding the exchange of momentum, heat, water,
and CO 2 between trees and the atmosphere is important to assess the impact of
drought, deforestation and climate change. Unfortunately, ground measurements of
tree properties such as mass and canopy interception of precipitation are often
expensive or difficult due to challenging environments. This paper aims to
demonstrate the concept of using robust and affordable accelerometers to measure
tree properties and responses. Tree sway is dependent on mass, canopy structure,
drag coefficient, and wind forcing. By measuring tree acceleration, we can relate
the tree motion to external forcing (e.g., wind, precipitation and related canopy
interception) and tree physical properties (e.g., mass, elasticity). Using five
months of acceleration data of 19 trees in the Brazilian Amazon, we show that the
frequency spectrum of tree sway is related to mass, canopy interception of
precipitation, and canopy-atmosphere turbulent exchange.
PMID- 28492479
TI - Fusion Based on Visible Light Positioning and Inertial Navigation Using Extended
Kalman Filters.
AB - With the rapid development of smart technology, the need for location-based
services (LBS) increases every day. Since classical positioning technology such
as GPS cannot satisfy the needs of indoor positioning, new indoor positioning
technologies, such as Bluetooth, Wi-Fi, and Visible light communication (VLC),
have already cut a figure. VLC positioning has been proposed because it has
higher accuracy, costs less, and is easier to accomplish in comparison to the
other indoor positioning technologies. However, the practicality of VLC
positioning is limited since it is easily affected by multipath effects and the
layout of LEDs. Thus, we propose a fusion positioning system based on extended
Kalman filters, which can fuse the VLC position and the inertial navigation data.
The accuracy of the fusion positioning system is in centimeters, which is better
compared to the VLC-based positioning or inertial navigation alone. Furthermore,
the fusion positioning system has high accuracy, saves energy, costs little, and
is easy to install, making it a promising candidate for future indoor positioning
applications.
PMID- 28492478
TI - The Role of the Orbitofrontal and Dorsolateral Prefrontal Cortices in Aesthetic
Preference for Art.
AB - The search for the underlying neural activation that occurs during subjective
aesthetic experiences of artwork has been enhanced through neuroimaging
techniques. Recently, the dorsolateral prefrontal cortex, alongside the
orbitofrontal cortex, have been implicated in aesthetic appreciation, and this is
the focus of the present paper. Here, the validity of this conclusion is examined
through the discussion of its neuroanatomical connections and functional
properties. It is proposed that the experimental evidence challenges the view
that this area could hold a privileged position in a brain network involved in
aesthetic preference.
PMID- 28492480
TI - Detection of Soil Nitrogen Using Near Infrared Sensors Based on Soil Pretreatment
and Algorithms.
AB - Soil nitrogen content is one of the important growth nutrient parameters of
crops. It is a prerequisite for scientific fertilization to accurately grasp soil
nutrient information in precision agriculture. The information about nutrients
such as nitrogen in the soil can be obtained quickly by using a near-infrared
sensor. The data can be analyzed in the detection process, which is
nondestructive and non-polluting. In order to investigate the effect of soil
pretreatment on nitrogen content by near infrared sensor, 16 nitrogen
concentrations were mixed with soil and the soil samples were divided into three
groups with different pretreatment. The first group of soil samples with strict
pretreatment were dried, ground, sieved and pressed. The second group of soil
samples were dried and ground. The third group of soil samples were simply dried.
Three linear different modeling methods are used to analyze the spectrum,
including partial least squares (PLS), uninformative variable elimination (UVE),
competitive adaptive reweighted algorithm (CARS). The model of nonlinear partial
least squares which supports vector machine (LS-SVM) is also used to analyze the
soil reflectance spectrum. The results show that the soil samples with strict
pretreatment have the best accuracy in predicting nitrogen content by near
infrared sensor, and the pretreatment method is suitable for practical
application.
PMID- 28492481
TI - A Vision-Aided 3D Path Teaching Method before Narrow Butt Joint Welding.
AB - For better welding quality, accurate path teaching for actuators must be achieved
before welding. Due to machining errors, assembly errors, deformations, etc., the
actual groove position may be different from the predetermined path. Therefore,
it is significant to recognize the actual groove position using machine vision
methods and perform an accurate path teaching process. However, during the
teaching process of a narrow butt joint, the existing machine vision methods may
fail because of poor adaptability, low resolution, and lack of 3D information.
This paper proposes a 3D path teaching method for narrow butt joint welding. This
method obtains two kinds of visual information nearly at the same time, namely 2D
pixel coordinates of the groove in uniform lighting condition and 3D point cloud
data of the workpiece surface in cross-line laser lighting condition. The 3D
position and pose between the welding torch and groove can be calculated after
information fusion. The image resolution can reach 12.5 MUm. Experiments are
carried out at an actuator speed of 2300 mm/min and groove width of less than 0.1
mm. The results show that this method is suitable for groove recognition before
narrow butt joint welding and can be applied in path teaching fields of 3D
complex components.
PMID- 28492483
TI - PCVMZM: Using the Probabilistic Classification Vector Machines Model Combined
with a Zernike Moments Descriptor to Predict Protein-Protein Interactions from
Protein Sequences.
AB - Protein-protein interactions (PPIs) are essential for most living organisms'
process. Thus, detecting PPIs is extremely important to understand the molecular
mechanisms of biological systems. Although many PPIs data have been generated by
high-throughput technologies for a variety of organisms, the whole interatom is
still far from complete. In addition, the high-throughput technologies for
detecting PPIs has some unavoidable defects, including time consumption, high
cost, and high error rate. In recent years, with the development of machine
learning, computational methods have been broadly used to predict PPIs, and can
achieve good prediction rate. In this paper, we present here PCVMZM, a
computational method based on a Probabilistic Classification Vector Machines
(PCVM) model and Zernike moments (ZM) descriptor for predicting the PPIs from
protein amino acids sequences. Specifically, a Zernike moments (ZM) descriptor is
used to extract protein evolutionary information from Position-Specific Scoring
Matrix (PSSM) generated by Position-Specific Iterated Basic Local Alignment
Search Tool (PSI-BLAST). Then, PCVM classifier is used to infer the interactions
among protein. When performed on PPIs datasets of Yeast and H. Pylori, the
proposed method can achieve the average prediction accuracy of 94.48% and 91.25%,
respectively. In order to further evaluate the performance of the proposed
method, the state-of-the-art support vector machines (SVM) classifier is used and
compares with the PCVM model. Experimental results on the Yeast dataset show that
the performance of PCVM classifier is better than that of SVM classifier. The
experimental results indicate that our proposed method is robust, powerful and
feasible, which can be used as a helpful tool for proteomics research.
PMID- 28492482
TI - Chromatin Switches during Neural Cell Differentiation and Their Dysregulation by
Prenatal Alcohol Exposure.
AB - Prenatal alcohol exposure causes persistent neuropsychiatric deficits included
under the term fetal alcohol spectrum disorders (FASD). Cellular identity emerges
from a cascade of intrinsic and extrinsic (involving cell-cell interactions and
signaling) processes that are partially initiated and maintained through changes
in chromatin structure. Prenatal alcohol exposure influences neuronal and
astrocyte development, permanently altering brain connectivity. Prenatal alcohol
exposure also alters chromatin structure through histone and DNA modifications.
However, the data linking alcohol-induced differentiation changes with
developmental alterations in chromatin structure remain to be elucidated. In the
first part of this review, we discuss the sequence of chromatin structural
changes involved in neural cell differentiation during normal development. We
then discuss the effects of prenatal alcohol on developmental histone
modifications and DNA methylation in the context of neurogenesis and
astrogliogenesis. We attempt to synthesize the developmental literature with the
FASD literature, proposing that alcohol-induced changes to chromatin structure
account for altered neurogenesis and astrogliogenesis as well as altered neuron
and astrocyte differentiation. Together these changes may contribute to the
cognitive and behavioral abnormalities in FASD. Future studies using standardized
alcohol exposure paradigms at specific developmental stages will advance the
understanding of how chromatin structural changes impact neural cell fate and
maturation in FASD.
PMID- 28492484
TI - The Potential of Triterpenoids from Loquat Leaves (Eriobotrya japonica) for
Prevention and Treatment of Skin Disorder.
AB - The leaves of loquat (Eriobotrya japonica) possess high medicinal value and have
been used as traditional medicines. However, there are no evidence-based studies
on the skin-care effects of E. japonica leaves. To explore new biological
activities of E. japonica leaves against skin disorder and to gain a better
understanding of the chemical components associated with bioactivities, we
evaluated 18 triterpenoids from E. japonica leaves on anti-melanogenesis, anti
acne, anti-allergy and anti-aging activities. Our results revealed that eight
compounds showed anti-melanogenesis activity, of which ursolic acid (1) and
maslinic acid (7) were the most potent with the similar selective index to that
of arbutin. Structure-activity relationship and possible mechanism of active
compounds were proposed. Twelve compounds exhibited anti-acne effect; ursolic
acid (1), maslinic acid (7), corosolic acid (8) and euscaphic acid (12) showed
highest activities against P. acnes. Four compounds displayed anti-allergy and
anti-inflammatory activity; 3-epicorosolic acid (9) and euscaphic acid (12)
showed marked activity against beta-hexosaminidase release. Finally, ursolic acid
(1), pomolic acid (10), colosolic acid (8) and its methylated derivative (6)
exhibited the highest anti-aging activity by stimulating collagen and hyaluronic
acid (HA) production. Our findings provide valuable evidence that E. japonica
leaves have potential applications as ingredients of function foods or cosmetics
for health benefits and a number of triterpenoids may play an important role in
these bioactivities.
PMID- 28492486
TI - A Human Activity Recognition System Based on Dynamic Clustering of Skeleton Data.
AB - Human activity recognition is an important area in computer vision, with its wide
range of applications including ambient assisted living. In this paper, an
activity recognition system based on skeleton data extracted from a depth camera
is presented. The system makes use of machine learning techniques to classify the
actions that are described with a set of a few basic postures. The training phase
creates several models related to the number of clustered postures by means of a
multiclass Support Vector Machine (SVM), trained with Sequential Minimal
Optimization (SMO). The classification phase adopts the X-means algorithm to find
the optimal number of clusters dynamically. The contribution of the paper is
twofold. The first aim is to perform activity recognition employing features
based on a small number of informative postures, extracted independently from
each activity instance; secondly, it aims to assess the minimum number of frames
needed for an adequate classification. The system is evaluated on two publicly
available datasets, the Cornell Activity Dataset (CAD-60) and the
Telecommunication Systems Team (TST) Fall detection dataset. The number of
clusters needed to model each instance ranges from two to four elements. The
proposed approach reaches excellent performances using only about 4 s of input
data (~100 frames) and outperforms the state of the art when it uses
approximately 500 frames on the CAD-60 dataset. The results are promising for the
test in real context.
PMID- 28492485
TI - Sulfated Alginates as Heparin Analogues: A Review of Chemical and Functional
Properties.
AB - Heparin is widely recognized for its potent anticoagulating effects, but has an
additional wide range of biological properties due to its high negative charge
and heterogeneous molecular structure. This heterogeneity has been one of the
factors in motivating the exploration of functional analogues with a more
predictable modification pattern and monosaccharide sequence, that can aid in
elucidating structure-function relationships and further be structurally
customized to fine-tune physical and biological properties toward novel
therapeutic applications and biomaterials. Alginates have been of great interest
in biomedicine due to their inherent biocompatibility, gentle gelling conditions,
and structural versatility from chemo-enzymatic engineering, but display limited
interactions with cells and biomolecules that are characteristic of heparin and
the other glycosaminoglycans (GAGs) of the extracellular environment. Here, we
review the chemistry and physical and biological properties of sulfated alginates
as structural and functional heparin analogues, and discuss how they may be
utilized in applications where the use of heparin and other sulfated GAGs is
challenging and limited.
PMID- 28492487
TI - Application of Soluplus to Improve the Flowability and Dissolution of Baicalein
Phospholipid Complex.
AB - In this study, a novel ternary complex system (TCS) composed of baicalein,
phospholipids, and Soluplus was prepared to improve the flowability and
dissolution for baicalein phospholipid complex (BPC). TCS was characterized using
differential scanning calorimetry (DSC), infrared spectroscopy (IR), powder X-ray
diffraction (PXRD), and scanning electron microscopy (SEM). The flowability,
solubility, oil-water partition coefficient, in vitro dissolution, and in vivo
pharmacokinetics of the system were also evaluated. DSC, IR, PXRD, and SEM data
confirmed that the crystal form of baicalein disappeared in BPC and TCS.
Furthermore, the angle of repose of TCS of 35 degrees indicated an improvement
in flowability, and solubility increased by approximately eight-fold in distilled
water when TCS was compared with BPC (41.00 +/- 4.89 MUg/mL vs. 5.00 +/- 0.16
MUg/mL). Approximately 91.24% of TCS was released at the end of 60 min in 0.5%
SDS (pH = 6.8), which suggested that TCS could improve the dissolution velocity
and extent. Moreover, TCS exhibited a considerable enhancement in bioavailability
with higher peak plasma concentration (25.55 MUg/mL vs. 6.05 MUg/mL) and
increased AUC0-infinity (62.47 MUg.h/mL vs. 50.48 MUg.h/mL) with 123.75% relative
bioavailability compared with BPC. Thus, Soluplus achieved the purpose of
improving the flowability and solubility of baicalein phospholipid complexes. The
application of Soluplus to phospholipid complexes has great potential.
PMID- 28492489
TI - An Automatic Localization Algorithm for Ultrasound Breast Tumors Based on Human
Visual Mechanism.
AB - Human visual mechanisms (HVMs) can quickly localize the most salient object in
natural images, but it is ineffective at localizing tumors in ultrasound breast
images. In this paper, we research the characteristics of tumors, develop a
classic HVM and propose a novel auto-localization method. Comparing to
surrounding areas, tumors have higher global and local contrast. In this method,
intensity, blackness ratio and superpixel contrast features are combined to
compute a saliency map, in which a Winner Take All algorithm is used to localize
the most salient region, which is represented by a circle. The results show that
the proposed method can successfully avoid the interference caused by background
areas of low echo and high intensity. The method has been tested on 400
ultrasound breast images, among which 376 images succeed in localization. This
means this method has a high accuracy of 94.00%, indicating its good performance
in real-life applications.
PMID- 28492488
TI - Redistribution of Cerebral Blood Flow during Severe Hypovolemia and Reperfusion
in a Sheep Model: Critical Role of alpha1-Adrenergic Signaling.
AB - BACKGROUND: Maintenance of brain circulation during shock is sufficient to
prevent subcortical injury but the cerebral cortex is not spared. This suggests
area-specific regulation of cerebral blood flow (CBF) during hemorrhage. METHODS:
Cortical and subcortical CBF were continuously measured during blood loss (<=50%)
and subsequent reperfusion using laser Doppler flowmetry. Blood gases, mean
arterial blood pressure (MABP), heart rate and renal blood flow were also
monitored. Urapidil was used for alpha1A-adrenergic receptor blockade in dosages,
which did not modify the MABP-response to blood loss. Western blot and
quantitative reverse transcription polymerase chain reactions were used to
determine adrenergic receptor expression in brain arterioles. RESULTS: During
hypovolemia subcortical CBF was maintained at 81 +/- 6% of baseline, whereas
cortical CBF decreased to 40 +/- 4% (p < 0.001). Reperfusion led to peak CBFs of
about 70% above baseline in both brain regions. alpha1A-Adrenergic blockade
massively reduced subcortical CBF during hemorrhage and reperfusion, and
prevented hyperperfusion during reperfusion in the cortex. alpha1A-mRNA
expression was significantly higher in the cortex, whereas alpha1D-mRNA
expression was higher in the subcortex (p < 0.001). CONCLUSIONS: alpha1
Adrenergic receptors are critical for perfusion redistribution: activity of the
alpha1A-receptor subtype is a prerequisite for redistribution of CBF, whereas the
alpha1D-receptor subtype may determine the magnitude of redistribution responses.
PMID- 28492490
TI - The Association between Parent Diet Quality and Child Dietary Patterns in Nine-
to Eleven-Year-Old Children from Dunedin, New Zealand.
AB - Previous research investigating the relationship between parents' and children's
diets has focused on single foods or nutrients, and not on global diet, which may
be more important for good health. The aim of the study was to investigate the
relationship between parental diet quality and child dietary patterns. A cross
sectional survey was conducted in 17 primary schools in Dunedin, New Zealand.
Information on food consumption and related factors in children and their primary
caregiver/parent were collected. Principal component analysis (PCA) was used to
investigate dietary patterns in children and diet quality index (DQI) scores were
calculated in parents. Relationships between parental DQI and child dietary
patterns were examined in 401 child-parent pairs using mixed regression models.
PCA generated two patterns; 'Fruit and Vegetables' and 'Snacks'. A one unit
higher parental DQI score was associated with a 0.03SD (CI: 0.02, 0.04) lower
child 'Snacks' score. There was no significant relationship between 'Fruit and
Vegetables' score and parental diet quality. Higher parental diet quality was
associated with a lower dietary pattern score in children that was characterised
by a lower consumption frequency of confectionery, chocolate, cakes, biscuits and
savoury snacks. These results highlight the importance of parental modelling, in
terms of their dietary choices, on the diet of children.
PMID- 28492491
TI - Magnetic Cationic Amylose Nanoparticles Used to Deliver Survivin-Small
Interfering RNA for Gene Therapy of Hepatocellular Carcinoma In Vitro.
AB - Amylose is a promising nanocarrier for gene delivery in terms of its good
biocompatibility and high transfection efficiency. Small interfering RNA against
survivin (survivin-siRNA) can cause tumor apoptosis by silencing a hepatocellular
carcinoma (HCC)-specific gene at the messenger RNA level. In this study, we
developed a new class of folate-functionalized, superparamagnetic iron oxide
(SPIO)-loaded cationic amylose nanoparticles to deliver survivin-siRNA to HCC
cells. The cellular uptake of nanocomplexes, cytotoxicity, cell apoptosis, and
gene suppression mediated by siRNA-complexed nanoparticles were tested. The
results demonstrated that folate-functionalized, SPIO-loaded cationic amylose
nanoparticles can mediate a specific and safe cellular uptake of survivin-siRNA
with high transfection efficiency, resulting in a robust survivin gene
downregulation in HCC cells. The biocompatible complex of cationic amylose could
be used as an efficient, rapid, and safe gene delivery vector. Upon SPIO loading,
it holds a great promise as a theranostic carrier for gene therapy of HCC.
PMID- 28492492
TI - The Effect of Dietary Glycemic Properties on Markers of Inflammation, Insulin
Resistance, and Body Composition in Postmenopausal American Women: An Ancillary
Study from a Multicenter Protein Supplementation Trial.
AB - Controversy exists as to whether high glycemic index/glycemic load (GI/GL) diets
increase the risk of chronic inflammation, which has been postulated as a
pathogenic intermediary between such diets and age-related alterations in body
composition and insulin resistance. We conducted an ancillary study to a
randomized, double-blind trial comparing the effects of a whey protein supplement
(PRO, n = 38) and a maltodextrin supplement (CHO, n = 46) on bone density to
evaluate the impact of a calibrated increase in GI/GL on inflammation, insulin
resistance, and body composition in a healthy aging population. Markers of
inflammation, HOMA, body composition, and GI/GL (estimated from 3-day food
records) were assessed at baseline and 18 months. By 18 months, the GL in the CHO
group increased by 34%, 88.4 +/- 5.2 -> 118.5 +/- 4.9 and did not change in the
PRO group, 86.5 +/- 4.1 -> 82.0 +/- 3.6 (p < 0.0001). Despite this change there
were no differences in serum CRP, IL-6, or HOMA at 18 months between the two
groups, nor were there significant associations between GL and inflammatory
markers. However, trunk lean mass (p = 0.0375) and total lean mass (p = 0.038)
were higher in the PRO group compared to the CHO group at 18 months There were
also significant associations for GL and change in total fat mass (r = 0.3, p =
0.01), change in BMI (r = 0.3, p = 0.005), and change in the lean-to-fat mass
ratio (r = -0.3, p = 0.002). Our data suggest that as dietary GL increases within
the moderate range, there is no detectable change in markers of inflammation or
insulin resistance, despite which there is a negative effect on body composition.
PMID- 28492493
TI - Hydration, Fluid Intake, and Related Urine Biomarkers among Male College Students
in Cangzhou, China: A Cross-Sectional Study-Applications for Assessing Fluid
Intake and Adequate Water Intake.
AB - The objectives of this study were to assess the associations between fluid intake
and urine biomarkers and to determine daily total fluid intake for assessing
hydration status for male college students. A total of 68 male college students
aged 18-25 years recruited from Cangzhou, China completed a 7-day cross-sectional
study. From day 1 to day 7; all subjects were asked to complete a self
administered 7-day 24-h fluid intake record. The foods eaten by subjects were
weighed and 24-h urine was collected for three consecutive days on the last three
consecutive days. On the sixth day, urine osmolality, specific gravity (USG), pH,
and concentrations of potassium, sodium, and chloride was determined. Subjects
were divided into optimal hydration, middle hydration, and hypohydration groups
according to their 24-h urine osmolality. Strong relationships were found between
daily total fluid intake and 24-h urine biomarkers, especially for 24-h urine
volume (r = 0.76; p < 0.0001) and osmolality (r = 0.76; p < 0.0001). The
percentage of the variances in daily total fluid intake (R2) explained by PLS
(partial least squares) model with seven urinary biomarkers was 68.9%; two urine
biomarkers-24-h urine volume and osmolality-were identified as possible key
predictors. The daily total fluid intake for assessing optimal hydration was 2582
mL, while the daily total fluid intake for assessing hypohydration was 2502 mL.
Differences in fluid intake and urine biomarkers were found among male college
students with different hydration status. A strong relationship existed between
urine biomarkers and fluid intake. A PLS model identified that key variables for
assessing daily total fluid intake were 24-h urine volume and osmolality. It was
feasibility to use total fluid intake to judge hydration status.
PMID- 28492495
TI - Immunotherapy for Colorectal Cancer.
AB - The recent success of anti-PD1 drugs in metastatic colorectal cancer patients
with mismatch repair deficiency generated overwhelming enthusiasm for
immunotherapy in the disease. However, patients with mismatch repair deficient
colorectal cancer represent only a small subset of the metastatic population.
Current research focuses on advancing immunotherapy to earlier stages of the
disease including adjuvant and first-line metastatic settings, and on inducing
sensitivity to immune checkpoint inhibitor therapy through a combinatorial
approach. Here, we review the contemporary understanding of the immune and
molecular landscape in colorectal cancer and discuss ongoing clinical trials
evaluating novel combination regimens based on immune checkpoint inhibitors.
PMID- 28492494
TI - Nasal Irrigation: An Imprecisely Defined Medical Procedure.
AB - Nasal irrigation (NI) is an old practice of upper respiratory tract care that
likely originated in the Ayurvedic medical tradition. It is used alone or in
association with other therapies in several conditions-including chronic
rhinosinusitis and allergic rhinitis-and to treat and prevent upper respiratory
tract infections, especially in children. However, despite it being largely
prescribed in everyday clinical practice, NI is not included or is only briefly
mentioned by experts in the guidelines for treatment of upper respiratory tract
diseases. In this review, present knowledge about NI and its relevance in
clinical practice is discussed to assist physicians in understanding the
available evidence and the potential use of this medical intervention. Analysis
of the literature showed that NI seems to be effective in the treatment of
several acute and chronic sinonasal conditions. However, although in recent years
several new studies have been performed, most of the studies that have evaluated
NI have relevant methodologic problems. Only multicenter studies enrolling a
great number of subjects can solve the problem of the real relevance of NI, and
these studies are urgently needed. Methods for performing NI have to be
standardized to determine which solutions, devices and durations of treatment are
adequate to obtain favorable results. This seems particularly important for
children that suffer a great number of sinonasal problems and might benefit
significantly from an inexpensive and simple preventive and therapeutic measure
such as NI.
PMID- 28492496
TI - Chemical Composition of Laurencia obtusa Extract and Isolation of a New C15
Acetogenin.
AB - A new C15-acetogenin, sagonenyne (20), exhibiting an unusual single
tetrahydropyran ring was isolated from an ethyl acetate extract of Laurencia
obtusa collected on the Corsican coastline. Its structure was established by
detailed NMR spectroscopic analysis, mass spectrometry, and comparison with
literature data. Twenty-three known compounds were identified in the same extract
by means of column chromatography steps, using a 13C-NMR computer aided method
developed in our laboratory. In addition to sesquiterpenes, which represent the
main chemical class of this extract, diterpenes, sterols, and C15-acetogenins
were identified. The crude extract was submitted to a cytotoxicity assay and was
particularly active against THP-1 cells, a human leukemia monocytic cell line.
PMID- 28492498
TI - Assessment of Inheritance and Fitness Costs Associated with Field-Evolved
Resistance to Cry3Bb1 Maize by Western Corn Rootworm.
AB - The western corn rootworm, Diabrotica virgifera virgifera LeConte, is among the
most serious insect pests of maize in North America. One strategy used to manage
this pest is transgenic maize that produces one or more crystalline (Cry) toxins
derived from the bacterium Bacillus thuringiensis (Bt). To delay Bt resistance by
insect pests, refuges of non-Bt maize are grown in conjunction with Bt maize. Two
factors influencing the success of the refuge strategy to delay resistance are
the inheritance of resistance and fitness costs, with greater delays in
resistance expected when inheritance of resistance is recessive and fitness costs
are present. We measured inheritance and fitness costs of resistance for two
strains of western corn rootworm with field-evolved resistance to Cry3Bb1 maize.
Plant-based and diet-based bioassays revealed that the inheritance of resistance
was non-recessive. In a greenhouse experiment, in which larvae were reared on
whole maize plants in field soil, no fitness costs of resistance were detected.
In a laboratory experiment, in which larvae experienced intraspecific and
interspecific competition for food, a fitness cost of delayed larval development
was identified, however, no other fitness costs were found. These findings of non
recessive inheritance of resistance and minimal fitness costs, highlight the
potential for the rapid evolution of resistance to Cry3Bb1 maize by western corn
rootworm, and may help to improve resistance management strategies for this pest.
PMID- 28492500
TI - An Introduction to the Toxins Special Issue on "Novel Pharmacological Inhibitors
for Bacterial Protein Toxins".
AB - n/a.
PMID- 28492497
TI - Regulation of TH17 Cells and Associated Cytokines in Wound Healing, Tissue
Regeneration, and Carcinogenesis.
AB - Wound healing is a crucial process which protects our body against permanent
damage and invasive infectious agents. Upon tissue damage, inflammation is an
early event which is orchestrated by a multitude of innate and adaptive immune
cell subsets including TH17 cells. TH17 cells and TH17 cell associated cytokines
can impact wound healing positively by clearing pathogens and modulating mucosal
surfaces and epithelial cells. Injury of the gut mucosa can cause fast expansion
of TH17 cells and their induction from naive T cells through Interleukin (IL)-6,
TGF-beta, and IL-1beta signaling. TH17 cells produce various cytokines, such as
tumor necrosis factor (TNF)-alpha, IL-17, and IL-22, which can promote cell
survival and proliferation and thus tissue regeneration in several organs
including the skin, the intestine, and the liver. However, TH17 cells are also
potentially pathogenic if not tightly controlled. Failure of these control
mechanisms can result in chronic inflammatory conditions, such as Inflammatory
Bowel Disease (IBD), and can ultimately promote carcinogenesis. Therefore, there
are several mechanisms which control TH17 cells. One control mechanism is the
regulation of TH17 cells via regulatory T cells and IL-10. This mechanism is
especially important in the intestine to terminate immune responses and maintain
homeostasis. Furthermore, TH17 cells have the potential to convert from a pro
inflammatory phenotype to an anti-inflammatory phenotype by changing their
cytokine profile and acquiring IL-10 production, thereby limiting their own
pathological potential. Finally, IL-22, a signature cytokine of TH17 cells, can
be controlled by an endogenous soluble inhibitory receptor, Interleukin 22
binding protein (IL-22BP). During tissue injury, the production of IL-22 by TH17
cells is upregulated in order to promote tissue regeneration. To limit the
regenerative program, which could promote carcinogenesis, IL-22BP is upregulated
during the later phase of regeneration in order to terminate the effects of IL
22. This delicate balance secures the beneficial effects of IL-22 and prevents
its potential pathogenicity. An important future goal is to understand the
precise mechanisms underlying the regulation of TH17 cells during inflammation,
wound healing, and carcinogenesis in order to design targeted therapies for a
variety of diseases including infections, cancer, and immune mediated
inflammatory disease.
PMID- 28492499
TI - Bioactive Natural Products of Marine Sponges from the Genus Hyrtios.
AB - Marine sponges are known as a rich source for novel bioactive compounds with
valuable pharmacological potential. One of the most predominant sponge genera is
Hyrtios, reported to have various species such as Hyrtios erectus, Hyrtios
reticulatus, Hyrtios gumminae, Hyrtios communis, and Hyrtios tubulatus and a
number of undescribed species. Members of the genus Hyrtios are a rich source of
natural products with diverse and valuable biological activities, represented by
different chemical classes including alkaloids, sesterterpenes and
sesquiterpenes. This review covers the literature until June 2016, providing a
complete survey of all compounds isolated from the genus Hyrtios with their
corresponding biological activities whenever applicable.
PMID- 28492501
TI - Urinary Metabolomics in Pediatric Obesity and NAFLD Identifies Metabolic
Pathways/Metabolites Related to Dietary Habits and Gut-Liver Axis Perturbations.
AB - To get insight into still elusive pathomechanisms of pediatric obesity and non
alcoholic fatty liver disease (NAFLD) we explored the interplay among GC-MS
studied urinary metabolomic signature, gut liver axis (GLA) abnormalities, and
food preferences (Kid-Med). Intestinal permeability (IP), small intestinal
bacterial overgrowth (SIBO), and homeostatic model assessment-insulin resistance
were investigated in forty children (mean age 9.8 years) categorized as normal
weight (NW) or obese (body mass index <85th or >95th percentile, respectively) +/
ultrasonographic bright liver and hypertransaminasemia (NAFLD). SIBO was
increased in all obese children (p = 0.0022), IP preferentially in those with
NAFLD (p = 0.0002). The partial least-square discriminant analysis of urinary
metabolome correctly allocated children based on their obesity, NAFLD, visceral
fat, pathological IP and SIBO. Compared to NW, obese children had (1) higher
levels of glucose/1-methylhistidine, the latter more markedly in NAFLD patients;
and (2) lower levels of xylitol, phenyl acetic acid and hydroquinone, the latter
especially in children without NAFLD. The metabolic pathways of BCAA and/or their
metabolites correlated with excess of visceral fat centimeters (leucine/oxo
valerate), and more deranged IP and SIBO (valine metabolites). Urinary metabolome
analysis contributes to define a metabolic fingerprint of pediatric obesity and
related NAFLD, by identifying metabolic pathways/metabolites reflecting typical
obesity dietary habits and GLA perturbations.
PMID- 28492502
TI - Caregiver Supervision Practices and Risk of Childhood Unintentional Injury
Mortality in Bangladesh.
AB - Unintentional injury-related mortality rate, including drowning among children
under five, is disproportionately higher in low- and middle-income countries. The
evidence links lapse of supervision with childhood unintentional injury deaths.
We determined the relationship between caregiver supervision and unintentional
injury mortality among children under five in rural Bangladesh. We conducted a
nested, matched, case-control study within the cohort of a large-scale drowning
prevention project in Bangladesh, "SOLID-Saving of Children's Lives from
Drowning". From the baseline survey of the project, 126 cases (children under
five with unintentional injury deaths) and 378 controls (alive children under
five) were selected at case-control ratio of 1:3 and individually matched on
neighborhood. The association between adult caregiver supervision and fatal
injuries among children under five was determined in a multivariable conditional
logistic regression analysis, and reported as adjusted matched odds ratio (MOR)
with 95% confidence intervals (CIs). Children under five experiencing death due
to unintentional injuries, including drowning, had 3.3 times increased odds of
being unsupervised as compared with alive children (MOR = 3.3, 95% CI: 1.6-7.0),
while adjusting for children's sex, age, socioeconomic index, and adult
caregivers' age, education, occupation, and marital status. These findings are
concerning and call for concerted, multi-sectoral efforts to design community
level prevention strategies. Public awareness and promotion of appropriate adult
supervision strategies are needed.
PMID- 28492504
TI - Optical Sensing to Determine Tomato Plant Spacing for Precise Agrochemical
Application: Two Scenarios.
AB - The feasibility of automated individual crop plant care in vegetable crop fields
has increased, resulting in improved efficiency and economic benefits. A systems
based approach is a key feature in the engineering design of mechanization that
incorporates precision sensing techniques. The objective of this study was to
design new sensing capabilities to measure crop plant spacing under different
test conditions (California, USA and Andalucia, Spain). For this study, three
different types of optical sensors were used: an optical light-beam sensor (880
nm), a Light Detection and Ranging (LiDAR) sensor (905 nm), and an RGB camera.
Field trials were conducted on newly transplanted tomato plants, using an encoder
as a local reference system. Test results achieved a 98% accuracy in detection
using light-beam sensors while a 96% accuracy on plant detections was achieved in
the best of replications using LiDAR. These results can contribute to the
decision-making regarding the use of these sensors by machinery manufacturers.
This could lead to an advance in the physical or chemical weed control on row
crops, allowing significant reductions or even elimination of hand-weeding tasks.
PMID- 28492503
TI - Synthetic Receptors Induce Anti Angiogenic and Stress Signaling on Human First
Trimester Cytotrophoblast Cells.
AB - The cytotrophoblast (CTB) cells of the human placenta have membrane receptors
that bind certain cardiotonic steroids (CTS) found in blood plasma. One of these,
marinobufagenin, is a key factor in the etiology of preeclampsia. Herein, we used
synthetic receptors (SR) to study their effectiveness on the angiogenic profile
of human first trimester CTB cells. The humanextravillous CTB cells (Sw.71) used
in this study were derived from first trimester chorionic villus tissue. Culture
media of CTB cells treated with >=1 nM SR level revealed sFlt-1 (Soluble fms-like
tyrosine kinase-1) was significantly increased while VEGF (vascular endothelial
growth factor) was significantly decreased in the culture media (* p < 0.05 for
each) The AT2 receptor (Angiotensin II receptor type 2) expression was
significantly upregulated in >=1 nM SR-treated CTB cells as compared to basal;
however, the AT1 (Angiotensin II receptor, type 1) and VEGFR-1 (vascular
endothelial growth factor receptor 1) receptor expression was significantly
downregulated (* p < 0.05 for each). Our results show that the anti-proliferative
and anti-angiogenic effects of SR on CTB cells are similar to the effects of CTS.
The observed anti angiogenic activity of SR on CTB cells demonstrates that the
functionalized-urea/thiourea molecules may be useful as potent inhibitors to
prevent CTS-induced impairment of CTB cells.
PMID- 28492505
TI - Mesoporous Silica Nanoparticles as Carriers for Intracellular Delivery of Nucleic
Acids and Subsequent Therapeutic Applications.
AB - Nucleic acids, including DNA, microRNA (miRNA), small interfering RNA (siRNA),
and antisense oligonucleotide (ASO), are powerful gene regulators, which have
been demonstrated as promising drug candidates for therapeutic treatments.
Nevertheless, poor cellular membrane permeability and serum stability have
greatly hindered the applications of nucleic acids in biomedicine. To address
these issues, associate carriers that can encapsulate and protect nucleic acids
are urgently required. Mesoporous silica nanoparticles (MSNs or MSNPs), which are
nanomaterials with excellent biocompatibility, large surface area for
functionalization, and tunable pore size for encapsulating different cargos, are
emerging as novel and ideal biomaterials for different biomedical applications.
In this review paper, we focus on the applications of MSNs in nucleic acid
delivery and nucleic acid-guided therapeutic treatments. General strategies for
the preparation of nucleic acid-MSN complexes will be firstly introduced,
followed by a summary of recent applications of MSNs in nucleic acid delivery and
nucleic acid-guided therapeutics.
PMID- 28492507
TI - Core-Shell Magnetic Gold Nanoparticles for Magnetic Field-Enhanced Radio
Photothermal Therapy in Cervical Cancer.
AB - The combination of radiotherapy (RT) and photothermal therapy (PTT) has been
considered an attractive strategy in cervical cancer treatment. However, it
remains a challenge to simultaneously enhance the radio-sensitivity of tumor
tissue, develop tumor tissue-focused radiation therapies and combine dual
therapeutic modalities. In this study, core-shell type magnetic gold (Fe3O4@Au)
nanoparticles are exploited to achieve the synergistic efficacy of radio
photothermal therapy in cervical cancer. Fe3O4@Au nanoparticles (NPs) with
uniform morphology exhibited superior surface plasmon resonance properties,
excellent superparamagnetic properties, good biocompatibility and high
photothermal conversion efficiency. For the in vitro tests, a low concentration
of Fe3O4@Au NPs after a short period of near-infrared irradiation lead to the
time-dependent death of cervical cancer cells. Further, the combination of RT and
PTT induced synergistic anti-cancer effects in vitro. More importantly, an
external magnetic field could significantly enhance the synergistic efficacy of
Fe3O4@Au NPs by improving their internalization. Hence, the reported Fe3O4@Au NPs
have the potential to be good nanoagents with excellent magnetic targeting
ability for cervical cancer radio-photothermal treatment.
PMID- 28492506
TI - Implementation of Objective PASC-Derived Taxon Demarcation Criteria for Official
Classification of Filoviruses.
AB - The mononegaviral family Filoviridae has eight members assigned to three genera
and seven species. Until now, genus and species demarcation were based on
arbitrarily chosen filovirus genome sequence divergence values (~50% for genera,
~30% for species) and arbitrarily chosen phenotypic virus or virion
characteristics. Here we report filovirus genome sequence-based taxon demarcation
criteria using the publicly accessible PAirwise Sequencing Comparison (PASC) tool
of the US National Center for Biotechnology Information (Bethesda, MD, USA).
Comparison of all available filovirus genomes in GenBank using PASC revealed
optimal genus demarcation at the 55-58% sequence diversity threshold range for
genera and at the 23-36% sequence diversity threshold range for species. Because
these thresholds do not change the current official filovirus classification,
these values are now implemented as filovirus taxon demarcation criteria that may
solely be used for filovirus classification in case additional data are absent. A
near-complete, coding-complete, or complete filovirus genome sequence will now be
required to allow official classification of any novel "filovirus."
Classification of filoviruses into existing taxa or determining the need for
novel taxa is now straightforward and could even become automated using a
presented algorithm/flowchart rooted in RefSeq (type) sequences.
PMID- 28492508
TI - Inclusion Complexes of a New Family of Non-Ionic Amphiphilic Dendrocalix[4]arene
and Poorly Water-Soluble Drugs Naproxen and Ibuprofen.
AB - The inclusion complexes of a new family of nonionic amphiphilic calix[4]arenes
with the anti-inflammatory hydrophobic drugs naproxen (NAP) and ibuprofen (IBP)
were investigated. The effects of the alkyl chain's length and the inner core of
calix[4]arenes on the interaction of the two drugs with the calix[4]arenes were
explored. The inclusion complexes of Amphiphiles 1a-c with NAP and IBP increased
the solubility of these drugs in aqueous media. The interaction of 1a-c with the
drugs in aqueous media was investigated through fluorescence, molecular modeling,
and 1H-NMR analysis. TEM studies further supported the formation of inclusion
complexes. The length of lipophilic alkyl chains and the intrinsic cyclic nature
of cailx[4]arene derivatives 1a-c were found to have a significant impact on the
solubility of NAP and IBP in pure water.
PMID- 28492509
TI - Transcriptomic Profiling of the Allorecognition Response to Grafting in the
Demosponge Amphimedon queenslandica.
AB - Sponges, despite their simple body plan, discriminate between self and nonself
with remarkable specificity. Sponge grafting experiments simulate the effects of
natural self or nonself contact under laboratory conditions. Here we take a
transcriptomic approach to investigate the temporal response to self and nonself
grafts in the marine demosponge Amphimedon queenslandica. Auto- and allografts
were established, observed and sampled over a period of three days, over which
time the grafts either rejected or accepted, depending on the identity of the
paired individuals, in a replicable and predictable manner. Fourteen
transcriptomes were generated that spanned the auto- and allograft responses.
Self grafts fuse completely in under three days, and the process appears to be
controlled by relatively few genes. In contrast, nonself grafting results in a
complete lack of fusion after three days, and appears to involve a broad
downregulation of normal biological processes, rather than the mounting of an
intense defensive response.
PMID- 28492510
TI - Special Issue: Ribozymes and RNA Catalysis.
AB - Over the past 35 years, RNA has become a molecule of utmost interest for
researchers in the life sciences. The many functions that RNA fulfills in the
cellular machinery have been elucidated with constant progress, revealing a
complex network of RNA-mediated regulation of key processes in the cellular life
cycle [...].
PMID- 28492511
TI - Impact of Maternal Selenium Status on Infant Outcome during the First 6 Months of
Life.
AB - Pregnant women and infants are at risk for selenium deficiency, which is known to
have negative effects on immune and brain function. We have investigated selenium
levels in 158 healthy never-pregnant women and in 114 pregnant and lactating
women and their infants at age 6 months and related this to clinical outcomes
during the first 6 months of life. Neurodevelopment was assessed with the
parental questionnaire Ages and Stages (ASQ) at 6 months. A maternal selenium
level <=0.90 umol/L in pregnancy week 18 was negatively related to infant
neurodevelopment at 6 months (B = -20, p = 0.01), whereas a selenium level <=0.78
umol/L in pregnancy week 36 was associated with an increased risk (odds ratio
4.8) of having an infant infection during the first 6 weeks of life. A low
maternal selenium status in pregnancy was found to be associated with an
increased risk of infant infection during the first 6 weeks of life and a lower
psychomotor score at 6 months. We suggest a cutoff for maternal serum selenium
deficiency of 0.90 umol/L in pregnancy week 18 and 0.78 umol/L in pregnancy week
36. This should be reevaluated in an intervention study.
PMID- 28492512
TI - Aldosterone and Mineralocorticoid Receptors-Physiology and Pathophysiology.
AB - Aldosterone is a uniquely terrestrial hormone, first appearing in lungfish, which
have both gills and lungs. Mineralocorticoid receptors (MRs), on the other hand,
evolved much earlier, and are found in cartilaginous and bony fish, presumptive
ligand cortisol. MRs have equivalent high affinity for aldosterone, progesterone,
and cortisol; in epithelia, despite much higher cortisol circulating levels,
aldosterone selectively activates MRs by co-expression of the enzyme 11beta
hydroxysteroid dehydrogenase, Type 11. In tissues in which the enzyme is not
expressed, MRs are overwhelmingly occupied but not activated by cortisol, which
normally thus acts as an MR antagonist; in tissue damage, however, cortisol
mimics aldosterone and acts as an MR agonist. The risk profile for primary
aldosteronism (PA) is much higher than that in age-, sex-, and blood pressure
matched essential hypertensives. High levels of aldosterone per se are not the
problem: in chronic sodium deficiency, as seen in the monsoon season in the
highlands of New Guinea, plasma aldosterone levels are extraordinarily high, but
cause neither hypertension nor cardiovascular damage. Such damage occurs when
aldosterone levels are out of the normal feedback control, and are
inappropriately elevated for the salt status of the individual (or experimental
animal). The question thus remains of how excess salt can synergize with elevated
aldosterone levels to produce deleterious cardiovascular effects. One possible
mechanism is through the agency of the elusive ouabain-like factors (OLFs). Such
factors are secreted from the adrenal in response to ACTH (adrenalocortical
tropic hormone), to angiotensin via AT2R, and-the polar opposite of aldosterone
to sodium loading. They act on blood vessels to cause vasoconstriction and thus
elevate blood pressure to dump excess sodium through pressure natriuresis. Their
levels are chronically elevated in PA in response to the continually elevated
sodium status, and they thus act to constrict coronary and systemic arteries. In
the context of the elevated blood volume and total body sodium in a PA patient,
this raises blood pressure and acts as the proximate cause of cardiovascular
damage. If this is the case, it would appear to offer new insights into therapy
for PA. One would be the use of digibindin, or its more recent successors as
antagonists of OLFs acting on Na/K ATPase at the vessel wall. A second would be
to routinely combine a low dose MR antagonist, an ENaC inhibitor, and sodium
restriction as first-line therapy for bilateral aldosterone overproduction.
Finally, for unilateral cases post-surgery, there is good reason to include low
dose MRs in drug therapy if required, given the ability of cortisol in damaged
blood vessels to mimic aldosterone vasoconstrictor action.
PMID- 28492514
TI - Operating Point Self-Regulator for Giant Magneto-Impedance Magnetic Sensor.
AB - The giant magneto-impedance (GMI) magnetic sensor based on the amorphous wire has
been believed to be tiny dimensions, high sensitivity, quick response, and small
power consumption. This kind of sensor is usually working under a bias magnetic
field that is called the sensor's operating point. However, the changes in
direction and intensity of the external magnetic field, or the changes in sensing
direction and position of the sensor, will lead to fluctuations in operating
point when the sensor is working without any magnetic shield. In this work, a GMI
sensor based on the operating point self-regulator is designed to overcome the
problem. The regulator is based on the compensated feedback control that can
maintain the operating point of a GMI sensor in a uniform position. With the
regulator, the GMI sensor exhibits a stable sensitivity regardless of the
external magnetic field. In comparison with the former work, the developed
operating point regulator can improve the accuracy and stability of the operating
point and therefore decrease the noise and disturbances that are introduced into
the GMI sensor by the previous self-regulation system.
PMID- 28492513
TI - An AAAG-Rich Oligodeoxynucleotide Rescues Mice from Bacterial Septic Peritonitis
by Interfering Interferon Regulatory Factor 5.
AB - A previous study found that an AAAG-rich Oligodeoxynucleotide (ODN), designated
as MS19, could lessen the acute lung inflammatory injury (ALII) in mice infected
by influenza viruses. Bioinformatics analysis found that MS19 is consensus with
the binding site of interferon regulatory factor 5 (IRF5) in the regulatory
elements of pro-inflammatory genes. This study established a septic peritonitis
model in Institute of Cancer Research (ICR) mice infected with Escherichia coli
(E. coli), and found that MS19 prolonged the survival of the mice and down
regulated the expression of inducible nitric oxide synthase (iNOS), interleukin-6
(IL-6), and tumor necrosis factor alpha (TNF-alpha). In cultured RAW264.7 cells,
MS19 significantly reduced the expression of iNOS, IRF5, IL-6, and TNF-alpha and
inhibited the nuclear translocation of IRF5. This data may provide a new insight
for understanding how MS19 reduces the excessive inflammatory responses in
sepsis.
PMID- 28492515
TI - Remote Sensing for Crop Water Management: From ET Modelling to Services for the
End Users.
AB - The experiences gathered during the past 30 years support the operational use of
irrigation scheduling based on frequent multi-spectral image data. Currently, the
operational use of dense time series of multispectral imagery at high spatial
resolution makes monitoring of crop biophysical parameters feasible, capturing
crop water use across the growing season, with suitable temporal and spatial
resolutions. These achievements, and the availability of accurate forecasting of
meteorological data, allow for precise predictions of crop water requirements
with unprecedented spatial resolution. This information is greatly appreciated by
the end users, i.e., professional farmers or decision-makers, and can be provided
in an easy-to-use manner and in near-real-time by using the improvements achieved
in web-GIS methodologies (Geographic Information Systems based on web
technologies). This paper reviews the most operational and explored methods based
on optical remote sensing for the assessment of crop water requirements,
identifying strengths and weaknesses and proposing alternatives to advance
towards full operational application of this methodology. In addition, we provide
a general overview of the tools, which facilitates co-creation and collaboration
with stakeholders, paying special attention to these approaches based on web-GIS
tools.
PMID- 28492517
TI - First Nations Approaches to Childhood Obesity: Healthy Lifestyles in Canada
Compared with Alternatives for Alaska Native Communities.
AB - Alaska Native and American Indian children have among the highest prevalence of
obesity in the United States. Canadian Aboriginal populations including First
Nations also have high rates of obesity but obesity rates among children are
noticeably lower. We highlight some of the important differences between American
and Canadian approaches to healthy lifestyles and Aboriginal/Native health,
including diet and physical activity, which may in part explain the differences
in obesity prevalence. Specifically, the Canadian government provides a food
subsidy program to bring perishable fruits and vegetable to remote, rural
Canadian areas and secondly supports the use of traditional foods and
harvesting/gathering through a number of government supported programs. Lastly,
there may be a better sense of community and overall life satisfaction for
Aboriginals compared with Alaska Natives, in part because of the incorporation of
healthcare and other services within the larger overall community, as opposed to
separate services as is the case for Alaska Natives. This perspective provides
insight into some of these potential differences.
PMID- 28492516
TI - Circulating Cell-Free DNA and Circulating Tumor Cells as Prognostic and
Predictive Biomarkers in Advanced Non-Small Cell Lung Cancer Patients Treated
with First-Line Chemotherapy.
AB - Cell-free DNA (cfDNA) and circulating tumor cells (CTCs) are promising prognostic
and predictive biomarkers in non-small cell lung cancer (NSCLC). In this study,
we examined the prognostic role of cfDNA and CTCs, in separate and joint
analyses, in NSCLC patients receiving first line chemotherapy. Seventy-three
patients with advanced NSCLC were enrolled in this study. CfDNA and CTC were
analyzed at baseline and after two cycles of chemotherapy. Plasma cfDNA
quantification was performed by quantitative PCR (qPCR) whereas CTCs were
isolated by the ScreenCell Cyto (ScreenCell, Paris, France) device and enumerated
according to malignant features. Patients with baseline cfDNA higher than the
median value (96.3 hTERT copy number) had a significantly worse overall survival
(OS) and double the risk of death (hazard ratio (HR): 2.14; 95% confidence limits
(CL) = 1.24-3.68; p-value = 0.006). Conversely, an inverse relationship between
CTC median baseline number (6 CTC/3 mL of blood) and OS was observed. In
addition, we found that in patients reporting stable disease (SD), the baseline
cfDNA and CTCs were able to discriminate patients at high risk of poor survival.
cfDNA demonstrated a more reliable biomarker than CTCs in the overall population.
In the subgroup of SD patients, both biomarkers identified patients at high risk
of poor prognosis who might deserve additional/alternative therapeutic
interventions.
PMID- 28492518
TI - Environmental Barriers to Participation of Preschool Children with and without
Physical Disabilities.
AB - Environment plays a vital role in affecting participation of young children in
home, school, and community. Knowledge of environmental barriers helps to develop
solutions or strategies that enable participation. The study compared the
environmental barriers perceived by parents of preschool children with physical
disabilities (PD, n = 142) and with typical development (TD, n = 192) in Taiwan.
Parents identified environmental barriers by structured interview using the
Chinese version of the Child and Adolescent Scale of Environment (CASE-C). The
CASE-C is an 18-item measure of the impact of problems with physical, social, and
attitudinal environmental features. Differences between the PD and TD groups in
the summary scores for the CASE-C and the percentages of parents who perceived a
problem for each item were examined by the analysis of covariance (ANCOVA) and
Chi-square test. Parents of children with PD more often identified barriers
related to family resources and community programs or services, social attitudes,
assistance and supports outside of home, physical design of home and community,
transportation, and assistive devices or equipment. Greater impacts of barriers
were also reported by parents of preschool children with PD. Our findings provide
evidence of environmental barriers that inform practice and policies to modify
the barriers and provide an accessible and inclusive environment for families
with young children.
PMID- 28492520
TI - An ecologically-controlled exoskeleton can improve balance recovery after
slippage.
AB - The evolution to bipedalism forced humans to develop suitable strategies for
dynamically controlling their balance, ensuring stability, and preventing
falling. The natural aging process and traumatic events such as lower-limb loss
can alter the human ability to control stability significantly increasing the
risk of fall and reducing the overall autonomy. Accordingly, there is an urgent
need, from both end-users and society, for novel solutions that can counteract
the lack of balance, thus preventing falls among older and fragile citizens. In
this study, we show a novel ecological approach relying on a wearable robotic
device (the Active Pelvis Orthosis, APO) aimed at facilitating balance recovery
after unexpected slippages. Specifically, if the APO detects signs of balance
loss, then it supplies counteracting torques at the hips to assist balance
recovery. Experimental tests conducted on eight elderly persons and two
transfemoral amputees revealed that stability against falls improved due to the
"assisting when needed" behavior of the APO. Interestingly, our approach required
a very limited personalization for each subject, and this makes it promising for
real-life applications. Our findings demonstrate the potential of closed-loop
controlled wearable robots to assist elderly and disabled subjects and to improve
their quality of life.
PMID- 28492521
TI - Coinjection of IL2 DNA enhances E7-specific antitumor immunity elicited by
intravaginal therapeutic HPV DNA vaccination with electroporation.
AB - The generation and use of therapeutic human papillomavirus (HPV) DNA vaccines
represent an appealing treatment method against HPV-associated cervical cancer
owing to their safety and durability. Previously, we created a therapeutic HPV
DNA vaccine candidate by linking the HPV16-E7 DNA sequence to calreticulin
(CRT/E7), which we showed could generate significant E7-specific cytotoxic T
lymphocyte (CTL)-mediated antitumor immune responses against HPV16 oncogenes
expressing murine tumor model TC-1. Here we assess the therapeutic efficacy of
intravaginal immunization with pcDNA3-CRT/E7 followed by electroporation. In
addition, we examined whether coadministration of DNA-encoding interleukin 2
(IL2) with the pcDNA3-CRT/E7 could improve the T-cell responses elicited by
pcDNA3-CRT/E7. TC-1 tumor-bearing mice vaccinated intravaginally with both pcDNA3
CRT/E7 and IL2 DNA followed by electroporation induced stronger local antitumor
CTL response in comparison to mice that received other treatment regimens.
Additionally, we found that coadministration of IL2 DNA with pcDNA3-CRT/E7
modified the tumor microenvironment by decreasing the population of regulatory T
cells and myeloid-derived suppressor cells relative to that of CTLs. Our data
demonstrate the translational potential of local administration of IL2 and pcDNA3
CRT/E7 followed by electroporation in treating cervicovaginal tumors.
PMID- 28492519
TI - Theranostic Probes for Targeting Tumor Microenvironment: An Overview.
AB - Long gone is the time when tumors were thought to be insular masses of cells,
residing independently at specific sites in an organ. Now, researchers gradually
realize that tumors interact with the extracellular matrix (ECM), blood vessels,
connective tissues, and immune cells in their environment, which is now known as
the tumor microenvironment (TME). It has been found that the interactions between
tumors and their surrounds promote tumor growth, invasion, and metastasis. The
dynamics and diversity of TME cause the tumors to be heterogeneous and thus pose
a challenge for cancer diagnosis, drug design, and therapy. As TME is significant
in enhancing tumor progression, it is vital to identify the different components
in the TME such as tumor vasculature, ECM, stromal cells, and the lymphatic
system. This review explores how these significant factors in the TME, supply
tumors with the required growth factors and signaling molecules to proliferate,
invade, and metastasize. We also examine the development of TME-targeted
nanotheranostics over the recent years for cancer therapy, diagnosis, and
anticancer drug delivery systems. This review further discusses the limitations
and future perspective of nanoparticle based theranostics when used in
combination with current imaging modalities like Optical Imaging, Magnetic
Resonance Imaging (MRI) and Nuclear Imaging (Positron Emission Tomography (PET)
and Single Photon Emission Computer Tomography (SPECT)).
PMID- 28492523
TI - Evaluation of identifier field agreement in linked neonatal records.
AB - OBJECTIVE: To better address barriers arising from missing and unreliable
identifiers in neonatal medical records, we evaluated agreement and discordance
among traditional and non-traditional linkage fields within a linked neonatal
data set. STUDY DESIGN: The retrospective, descriptive analysis represents
infants born from 2013 to 2015. We linked children's hospital neonatal physician
billing records to newborn medical records originating from an academic delivery
hospital and evaluated rates of agreement, discordance and missingness for a set
of 12 identifier field pairs used in the linkage algorithm. RESULTS: We linked
7293 of 7404 physician billing records (98.5%), all of which were deemed valid
upon manual review. Linked records contained a mean of 9.1 matching and 1.6 non
matching identifier pairs. Only 4.8% had complete agreement among all 12
identifier pairs. CONCLUSION: Our approach to selection of linkage variables and
data formatting preparatory to linkage have generalizability, which may inform
future neonatal and perinatal record linkage efforts.
PMID- 28492522
TI - Impact of brain injury on functional measures of amplitude-integrated EEG at term
equivalent age in premature infants.
AB - OBJECTIVE: To evaluate the association between qualitative and quantitative
amplitude-integrated EEG (aEEG) measures at term equivalent age (TEA) and brain
injury on magnetic resonance imaging (MRI) in preterm infants. STUDY DESIGN: A
cohort of premature infants born at <30 weeks of gestation and with moderate-to
severe MRI injury on a TEA MRI scan was identified. A contemporaneous group of
gestational age-matched control infants also born at <30 weeks of gestation with
none/mild injury on MRI was also recruited. Quantitative aEEG measures, including
maximum and minimum amplitudes, bandwidth span and spectral edge frequency
(SEF90), were calculated using an offline software package. The aEEG recordings
were qualitatively scored using the Burdjalov system. MRI scans, performed on the
same day as aEEG, occurred at a mean postmenstrual age of 38.0 (range 37 to 42)
weeks and were scored for abnormality in a blinded manner using an established
MRI scoring system. RESULTS: Twenty-eight (46.7%) infants had a normal MRI or
mild brain abnormality, while 32 (53.3%) infants had moderate-to-severe brain
abnormality. Univariate regression analysis demonstrated an association between
severity of brain abnormality and quantitative measures of left and right SEF90
and bandwidth span (beta=-0.38, -0.40 and 0.30, respectively) and qualitative
measures of cyclicity, continuity and total Burdjalov score (beta=-0.10, -0.14
and -0.12, respectively). After correcting for confounding variables, the
relationship between MRI abnormality score and aEEG measures of SEF90, bandwidth
span and Burdjalov score remained significant. CONCLUSION: Brain abnormalities on
MRI at TEA in premature infants are associated with abnormalities on term aEEG
measures, suggesting that anatomical brain injury may contribute to delay in
functional brain maturation as assessed using aEEG.
PMID- 28492524
TI - Sociodemographic and attitudinal predictors of simultaneous and redundant
multiple marker and cell-free DNA screening among women aged ?35 years.
AB - OBJECTIVE: To identify characteristics associated with undergoing cell-free DNA
(cfDNA) and multiple marker screening (MMS) simultaneously or redundantly (after
receiving negative results from the first screening test) among women aged ?35
years. STUDY DESIGN: Participants presenting for prenatal testing completed a
questionnaire that included measures of pregnancy worry and attitudes toward
potential testing outcomes; data on prenatal test use was obtained via medical
record review. We used multivariable logistic regression to identify factors
associated with redundant or simultaneous screening. RESULTS: Among 164
participants, 69 (42.1%) had cfDNA redundantly (n=51) to, or simultaneously
(n=18) with, MMS. Compared with the 46 MMS-negative women who did not undergo
further testing, those who underwent redundant or simultaneous cfDNA/MMS
screening were more likely to have annual family incomes >$150 000, to feel
having a miscarriage would be worse than having an intellectually disabled child,
to desire comprehensive testing for intellectual disability and to have more
pregnancy worry. CONCLUSION: Providers who counsel patients on prenatal
aneuploidy screening tests should explain the appropriate utilization of these
screening tests to avoid unnecessary or minimally informative use of multiple
tests.
PMID- 28492525
TI - Neonatal sepsis in rural India: timing, microbiology and antibiotic resistance in
a population-based prospective study in the community setting.
AB - OBJECTIVE: To examine the timing and microbiology of neonatal sepsis in a
population-based surveillance in the Indian community setting. STUDY DESIGN: All
live born infants in 223 villages of Odisha state were followed at home for 60
days. Suspect sepsis cases were referred to study hospitals for further
evaluation including blood culture. RESULTS: Of 12 622 births, 842 were admitted
with suspected sepsis of whom 95% were 4 to 60 days old. Culture-confirmed
incidence of sepsis was 6.7/1000 births with 51% Gram negatives (Klebsiella
predominating) and 26% Gram positives (mostly Staphylococcus aureus). A very high
level of resistance to penicillin and ampicillin, moderate resistance to
cephalosporins and extremely low resistance to Gentamicin and Amikacin was
observed. CONCLUSION: The bacterial burden of sepsis in the Indian community is
not high. Judicious choice of empiric antibiotics, antibiotic stewardship and
alternate modalities should be considered for the management or prevention of
neonatal sepsis in India.
PMID- 28492527
TI - Single-cell template strand sequencing by Strand-seq enables the characterization
of individual homologs.
AB - The ability to distinguish between genome sequences of homologous chromosomes in
single cells is important for studies of copy-neutral genomic rearrangements
(such as inversions and translocations), building chromosome-length haplotypes,
refining genome assemblies, mapping sister chromatid exchange events and
exploring cellular heterogeneity. Strand-seq is a single-cell sequencing
technology that resolves the individual homologs within a cell by restricting
sequence analysis to the DNA template strands used during DNA replication. This
protocol, which takes up to 4 d to complete, relies on the directionality of DNA,
in which each single strand of a DNA molecule is distinguished based on its 5'-3'
orientation. Culturing cells in a thymidine analog for one round of cell division
labels nascent DNA strands, allowing for their selective removal during genomic
library construction. To preserve directionality of template strands, genomic
preamplification is bypassed and labeled nascent strands are nicked and not
amplified during library preparation. Each single-cell library is multiplexed for
pooling and sequencing, and the resulting sequence data are aligned, mapping to
either the minus or plus strand of the reference genome, to assign template
strand states for each chromosome in the cell. The major adaptations to
conventional single-cell sequencing protocols include harvesting of daughter
cells after a single round of BrdU incorporation, bypassing of whole-genome
amplification, and removal of the BrdU+ strand during Strand-seq library
preparation. By sequencing just template strands, the structure and identity of
each homolog are preserved.
PMID- 28492529
TI - CORRIGENDUM: ACMG recommendations for reporting of incidental findings in
clinical exome and genome sequencing.
PMID- 28492526
TI - Differentiation of cardiomyocytes and generation of human engineered heart
tissue.
AB - Since the advent of the generation of human induced pluripotent stem cells
(hiPSCs), numerous protocols have been developed to differentiate hiPSCs into
cardiomyocytes and then subsequently assess their ability to recapitulate the
properties of adult human cardiomyocytes. However, hiPSC-derived cardiomyocytes
(hiPSC-CMs) are often assessed in single-cell assays. A shortcoming of these
assays is the limited ability to characterize the physiological parameters of
cardiomyocytes, such as contractile force, due to random orientations. This
protocol describes the differentiation of cardiomyocytes from hiPSCs, which
occurs within 14 d. After casting, cardiomyocytes undergo 3D assembly. This
produces fibrin-based engineered heart tissues (EHTs)-in a strip format-that
generate force under auxotonic stretch conditions. 10-15 d after casting, the
EHTs can be used for contractility measurements. This protocol describes parallel
expansion of hiPSCs; standardized generation of defined embryoid bodies, growth
factor and small-molecule-based cardiac differentiation; and standardized
generation of EHTs. To carry out the protocol, experience in advanced cell
culture techniques is required.
PMID- 28492530
TI - A comprehensive strategy for exome-based preconception carrier screening.
AB - PURPOSE: Whole-exome sequencing (WES) provides the possibility of genome-wide
preconception carrier screening (PCS). Here, we propose a filter strategy to
rapidly identify the majority of relevant pathogenic mutations. METHODS: Our
strategy was developed using WES data from eight consanguineous and five fictive
nonconsanguineous couples and was subsequently applied to 20 other fictive
nonconsanguineous couples. Presumably pathogenic variants based on frequency and
database annotations or generic characteristics and mutation type were selected
in genes shared by the couple and in the female's X-chromosome. Unclassified
variants were not included. RESULTS: This yielded an average of 29 (19-51)
variants in genes shared by the consanguineous couples and 15 (6-30) shared by
the nonconsanguineous couples. For X-linked variants, the numbers per female were
3 (1-5) and 1 (0-3), respectively. Remaining variants were verified manually. The
majority were able to be quickly discarded, effectively leaving true pathogenic
variants. CONCLUSION: We conclude that WES is applicable for PCS, both for
consanguineous and nonconsanguineous couples, with the remaining number of
variants being manageable in a clinical setting. The addition of gene panels for
filtering was not favorable because it resulted in missing pathogenic variants.
It is important to develop and continuously curate databases with pathogenic
mutations to further increase the sensitivity of WES-based PCS.Genet Med advance
online publication 27 October 2016.
PMID- 28492531
TI - Improving the evaluation of milestones for students completing a clinical
genetics elective.
PMID- 28492532
TI - Sherloc: a comprehensive refinement of the ACMG-AMP variant classification
criteria.
AB - PurposeThe 2015 American College of Medical Genetics and Genomics-Association for
Molecular Pathology (ACMG-AMP) guidelines were a major step toward establishing a
common framework for variant classification. In practice, however, several
aspects of the guidelines lack specificity, are subject to varied
interpretations, or fail to capture relevant aspects of clinical molecular
genetics. A simple implementation of the guidelines in their current form is
insufficient for consistent and comprehensive variant classification.MethodsWe
undertook an iterative process of refining the ACMG-AMP guidelines. We used the
guidelines to classify more than 40,000 clinically observed variants, assessed
the outcome, and refined the classification criteria to capture exceptions and
edge cases. During this process, the criteria evolved through eight major and
minor revisions.ResultsOur implementation: (i) separated ambiguous ACMG-AMP
criteria into a set of discrete but related rules with refined weights; (ii)
grouped certain criteria to protect against the overcounting of conceptually
related evidence; and (iii) replaced the "clinical criteria" style of the
guidelines with additive, semiquantitative criteria.ConclusionSherloc builds on
the strong framework of 33 rules established by the ACMG-AMP guidelines and
introduces 108 detailed refinements, which support a more consistent and
transparent approach to variant classification.
PMID- 28492534
TI - Response to de Vries et al.
PMID- 28492533
TI - Gene patents still alive and kicking: their impact on provision of genetic
testing for long QT syndrome in the Canadian public health-care system.
AB - PurposeAlthough the Supreme Court of the United States limited their availability
in Association for Molecular Pathology v. Myriad Genetics, gene patents remain
important around the world. We examine the situation in Canada, where gene
patents continue to exist, in light of recent litigation relating to familial
long QT syndrome (LQTS).MethodsWe conducted in-depth semistructured interviews
with 25 stakeholders across five Canadian provinces and supplemented this with a
case analysis of the litigation.ResultsThe majority of LQTS testing was carried
out outside Canada. Rising costs prompted several provinces to attempt to
repatriate testing. However, LQTS gene patents stymied efforts, particularly in
provinces where testing was more centralized, increasing costs and lowering
innovation. It was in this context that a hospital launched a test case against
the LQTS patents, resulting in a novel agreement to free Canadian hospitals from
the effects of patents.ConclusionOur analysis reveals a rapidly evolving genetic
test provision landscape under pressure from gene patents, strained budgets and
poor collaboration. The litigation resulted in a blueprint for free public use of
gene patents throughout Canada's health-care system, but it will only have value
if governments are proactive in its use.
PMID- 28492535
TI - Response to Laissue et al.
PMID- 28492536
TI - Quantifying family dissemination and identifying barriers to communication of
risk information in Australian BRCA families.
AB - PurposeRecommendations for BRCA1 and BRCA2 mutation carriers to disseminate
information to at-risk relatives pose significant challenges. This study aimed to
quantify family dissemination, to explain the differences between fully informed
families (all relatives informed verbally or in writing) and partially informed
families (at least one relative uninformed), and to identify dissemination
barriers.MethodsBRCA1 and BRCA2 mutation carriers identified from four Australian
hospitals (n=671) were invited to participate in the study. Distress was measured
at consent using the Kessler psychological distress scale (K10). A structured
telephone interview was used to assess the informed status of relatives,
geographical location of relatives, and dissemination barriers. Family
dissemination was quantified, and fully versus partially informed family
differences were examined. Dissemination barriers were thematically coded and
counted.ResultsA total of 165 families participated. Information had been
disseminated to 81.1% of relatives. At least one relative had not been informed
in 52.7% of families, 4.3% were first-degree relatives, 27.0% were second-degree
relatives, and 62.0% were cousins. Partially informed families were significantly
larger than fully informed families, had fewer relatives living in close
proximity, and exhibited higher levels of distress. The most commonly recorded
barrier to dissemination was loss of contact.ConclusionLarger, geographically
diverse families have greater difficulty disseminating BRCA mutation risk
information to all relatives. Understanding these challenges can inform future
initiatives for communication, follow-up and support.
PMID- 28492537
TI - Advantages and Some Remaining Challenges in Hereditary Gastrointestinal Cancer
Panel Testing.
AB - Colorectal cancer affects 1 in 20 men and women in their lifetime. About 30% of
these cases have been shown to be familial while only about 5% are associated
with a highly penetrant hereditary colon cancer syndrome. In many familial cases,
however, no mutation in the commonly implicated CRC genes is found. With the
development of next-generation sequencing, testing laboratories are now able to
offer hereditary gastrointestinal panel testing, which allows for the
simultaneous sequencing of a much broader set of genes associated with CRC. We
discuss the advantages and disadvantages of such testing to inform best clinical
practice.
PMID- 28492538
TI - Drosophila caspase activity is required independently of apoptosis to produce
active TNF/Eiger during nociceptive sensitization.
AB - Tumor necrosis factor (TNF) signaling is required for inflammatory nociceptive
(pain) sensitization in Drosophila and vertebrates. Nociceptive sensitization in
Drosophila larvae following UV-induced tissue damage is accompanied by epidermal
apoptosis and requires epidermal-derived TNF/Eiger and the initiator caspase,
Dronc. Major gaps remain regarding TNF function in sensitization, including the
relationship between apoptosis/tissue damage and TNF production, the downstream
signaling in this context, and the target genes that modulate nociceptive
behaviors. Here, apoptotic cell death and thermal nociceptive sensitization are
genetically and procedurally separable in a Drosophila model of UV-induced
nociceptive sensitization. Activation of epidermal Dronc induces TNF-dependent
but effector caspase-independent nociceptive sensitization in the absence of UV.
In addition, knockdown of Dronc attenuated nociceptive sensitization induced by
full-length TNF/Eiger but not by a constitutively soluble form. UV irradiation
induced TNF production in both in vitro and in vivo, but TNF secretion into
hemolymph was not sufficient to induce thermal nociceptive sensitization.
Downstream mediators of TNF-induced sensitization included two TNF receptor
associated factors, a p38 kinase, and the transcription factor nuclear factor
kappa B. Finally, sensory neuron-specific microarray analysis revealed downstream
TNF target genes induced during thermal nociceptive sensitization. One of these,
enhancer of zeste (E(z)), functions downstream of TNF during thermal nociceptive
sensitization. Our findings suggest that an initiator caspase is involved in TNF
processing/secretion during nociceptive sensitization, and that TNF activation
leads to a specific downstream signaling cascade and gene transcription required
for sensitization. These findings have implications for both the evolution of
inflammatory caspase function following tissue damage signals and the action of
TNF during sensitization in vertebrates.
PMID- 28492539
TI - Non-junctional Cx32 mediates anti-apoptotic and pro-tumor effects via epidermal
growth factor receptor in human cervical cancer cells.
AB - The role of connexin proteins (Cx), which form gap junctions (GJ), in progression
and chemotherapeutic sensitivity of cervical cancer (CaCx), is unclear. Using
cervix specimens (313 CaCx, 78 controls) and CaCx cell lines, we explored
relationships among Cx expression, prognostic variables and mechanisms that may
link them. In CaCx specimens, Cx32 was upregulated and cytoplasmically localized,
and three other Cx downregulated, relative to controls. Cx32 expression
correlated with advanced FIGO staging, differentiation and increased tumor size.
In CaCx cell lines, Cx32 expression suppressed streptonigrin/cisplatin-induced
apoptosis in the absence of functional GJ. In CaCx specimens and cell lines,
expression of Cx32 upregulated epidermal growth factor receptor (EGFR)
expression. Inhibition of EGFR signaling abrogated the anti-apoptotic effect of
Cx32 expression. In conclusion, upregulated Cx32 in CaCx cells produces anti
apoptotic, pro-tumorigenic effects in vivo and vitro. Abnormal Cx32
expression/localization in CaCx appears to be both a mechanism and biomarker of
chemotherapeutic resistance.
PMID- 28492540
TI - NMI inhibits cancer stem cell traits by downregulating hTERT in breast cancer.
AB - N-myc and STAT interactor (NMI) has been proved to bind to different
transcription factors to regulate a variety of signaling mechanisms including DNA
damage, cell cycle and epithelial-mesenchymal transition. However, the role of
NMI in the regulation of cancer stem cells (CSCs) remains poorly understood. In
this study, we investigated the regulation of NMI on CSCs traits in breast cancer
and uncovered the underlying molecular mechanisms. We found that NMI was lowly
expressed in breast cancer stem cells (BCSCs)-enriched populations. Knockdown of
NMI promoted CSCs traits while its overexpression inhibited CSCs traits,
including the expression of CSC-related markers, the number of CD44+CD24- cell
populations and the ability of mammospheres formation. We also found that NMI
mediated regulation of BCSCs traits was at least partially realized through the
modulation of hTERT signaling. NMI knockdown upregulated hTERT expression while
its overexpression downregulated hTERT in breast cancer cells, and the changes in
CSCs traits and cell invasion ability mediated by NMI were rescued by hTERT. The
in vivo study also validated that NMI knockdown promoted breast cancer growth by
upregulating hTERT signaling in a mouse model. Moreover, further analyses for the
clinical samples demonstrated that NMI expression was negatively correlated with
hTERT expression and the low NMI/high hTERT expression was associated with the
worse status of clinical TNM stages in breast cancer patients. Furthermore, we
demonstrated that the interaction of YY1 protein with NMI and its involvement in
NMI-mediated transcriptional regulation of hTERT in breast cancer cells.
Collectively, our results provide new insights into understanding the regulatory
mechanism of CSCs and suggest that the NMI-YY1-hTERT signaling axis may be a
potential therapeutic target for breast cancers.
PMID- 28492541
TI - Glycolysis regulates the expansion of myeloid-derived suppressor cells in tumor
bearing hosts through prevention of ROS-mediated apoptosis.
AB - Immunotherapy aiming to rescue or boost antitumor immunity is an emerging
strategy for treatment of cancers. The efficacy of immunotherapy is strongly
controlled by the immunological milieu of cancer patients. Myeloid-derived
suppressor cells (MDSCs) are heterogeneous immature myeloid cell populations with
immunosuppressive functions accumulating in individuals during tumor progression.
The signaling mechanisms of MDSC activation have been well studied. However,
there is little known about the metabolic status of MDSCs and the physiological
role of their metabolic reprogramming. In this study, we discovered that myeloid
cells upregulated their glycolytic genes when encountered with tumor-derived
factors. MDSCs exhibited higher glycolytic rate than their normal cell
compartment did, which contributed to the accumulation of the MDSCs in tumor
bearing hosts. Upregulation of glycolysis prevented excess reactive oxygen
species (ROS) production by MDSCs, which protected MDSCs from apoptosis. Most
importantly, we identified the glycolytic metabolite, phosphoenolpyruvate (PEP),
as a vital antioxidant agent able to prevent excess ROS production and therefore
contributed to the survival of MDSCs. These findings suggest that glycolytic
metabolites have important roles in the modulation of fitness of MDSCs and could
be potential targets for anti-MDSC strategy. Targeting MDSCs with analogs of
specific glycolytic metabolites, for example, 2-phosphoglycerate or PEP may
diminish the accumulation of MDSCs and reverse the immunosuppressive milieu in
tumor-bearing individuals.
PMID- 28492542
TI - LncRNA HOTAIR regulates HIF-1alpha/AXL signaling through inhibition of miR-217 in
renal cell carcinoma.
AB - Long non-coding RNA HOTAIR was regarded as an oncogene in multiple cancers.
Previous studies have shown that HOTAIR is involved in the proliferation and
tumorigenesis of renal carcinoma cells, while microRNA (miR)-217 functions as a
tumor suppressor in renal cell carcinoma (Rcc). However, the underlying molecular
mechanism of HOTAIR in Rcc, especially in association with miR-217, has not been
studied. In this study, we first demonstrated that HOTAIR expression was
upregulated, which was correlated with tumor progression, and miR-217
downregulated in Rcc tissues and cells. Importantly, HOTAIR expression was
negatively correlated with miR-217 expression in Rcc tissues. Gain- and loss-of
function of HOTAIR revealed that HOTAIR functioned as a ceRNA for miR-217 to
facilitate HIF-1alpha expression and then upregulated AXL level promoting Rcc
proliferation, migration, and EMT process, and inhibiting apoptosis. Furthermore,
HOTAIR knockdown suppressed tumor growth and reduced the expression of
proliferation antigen ki-67, HIF-1alpha, and AXL, but upregulated the expression
of miR-217 in vivo. Finally, with AXL inhibitor BGB324, we confirmed that HOTAIR
promoted Rcc activity through AXL signaling both in vitro and in vivo. In
conclusion, these results suggest that HOTAIR promotes Rcc tumorigenesis via miR
217/HIF-1alpha/AXL signaling, which may provide a new target for the diagnosis
and therapy of Rcc disease.
PMID- 28492543
TI - BASP1 interacts with oestrogen receptor alpha and modifies the tamoxifen
response.
AB - Tamoxifen binds to oestrogen receptor alpha (ERalpha) to elicit distinct
responses that vary by cell/tissue type and status, but the factors that
determine these differential effects are unknown. Here we report that the
transcriptional corepressor BASP1 interacts with ERalpha and in breast cancer
cells, this interaction is enhanced by tamoxifen. We find that BASP1 acts as a
major selectivity factor in the transcriptional response of breast cancer cells
to tamoxifen. In all, 40% of the genes that are regulated by tamoxifen in breast
cancer cells are BASP1 dependent, including several genes that are associated
with tamoxifen resistance. BASP1 elicits tumour-suppressor activity in breast
cancer cells and enhances the antitumourigenic effects of tamoxifen treatment.
Moreover, BASP1 is expressed in breast cancer tissue and is associated with
increased patient survival. Our data have identified BASP1 as an ERalpha cofactor
that has a central role in the transcriptional and antitumourigenic effects of
tamoxifen.
PMID- 28492544
TI - Halofuginone dually regulates autophagic flux through nutrient-sensing pathways
in colorectal cancer.
AB - Autophagy has a key role in metabolism and impacts on tumorigenesis. Our previous
study found that halofuginone (HF) exerts anticancer activity in colorectal
cancer (CRC) by downregulating Akt/mTORC1 (mechanistic target of rapamycin
complex 1) signaling pathway. But whether and how HF regulates autophagy and
metabolism to inhibit cancer growth remains an open question. Here, we unveil
that HF activates ULK1 by downregulation of its phosphorylation site at Ser757
through Akt/mTORC1 signaling pathway, resulting in induction of autophagic flux
under nutrient-rich condition. On the other hand, HF inactivates ULK1 by
downregulation of its phosphorylation sites at Ser317 and Ser777 through
LKB1/AMPK signaling pathway, resulting in autophagic inhibition under nutrient
poor condition. Furthermore, Atg7-dependent autophagosome formation is also
induced under nutrient-rich condition or blocked in nutrient-poor environment,
respectively, upon HF treatment. More interestingly, we also found that HF
inhibits glycolysis under nutrient-rich condition, whereas inhibits
gluconeogenesis under nutrient-poor condition in an Atg7-dependent manner,
suggesting that autophagy has a pivotal role of glucose metabolism upon HF
treatment. Subsequent studies showed that HF treatment retarded tumor growth in
xenograft mice fed with either standard chow diet or caloric restriction through
dual regulation of autophagy in vivo. Together, HF has a dual role in autophagic
modulation depending on nutritional conditions for anti-CRC.
PMID- 28492545
TI - Chronically stressed or stress-preconditioned neurons fail to maintain stress
granule assembly.
AB - Dysregulation of stress granules (SGs) and their resident proteins contributes to
pathogenesis of a number of (neuro)degenerative diseases. Phosphorylation of
eIF2alpha is an event integrating different types of cellular stress and it is
required for SG assembly. Phosphorylated eIF2alpha (p-eIF2alpha) is upregulated
in the nervous system in some neurodegenerative conditions. We found that
increasing p-eIF2alpha level by proteasomal inhibition in cultured cells,
including mouse and human neurons, before a SG-inducing stress ('stress
preconditioning'), limits their ability to maintain SG assembly. This is due to
upregulation of PP1 phosphatase regulatory subunits GADD34 and/or CReP in
preconditioned cells and early decline of p-eIF2alpha levels during subsequent
acute stress. In two model systems with constitutively upregulated p-eIF2alpha,
mouse embryonic fibroblasts lacking CReP and brain neurons of tau transgenic
mice, SG formation was also impaired. Thus, neurons enduring chronic stress or
primed by a transient mild stress fail to maintain p-eIF2alpha levels following
subsequent acute stress, which would compromise protective function of SGs. Our
findings provide experimental evidence on possible loss of function for SGs in
certain neurodegenerative diseases.
PMID- 28492547
TI - Autophagy is essential for hearing in mice.
AB - Hearing loss is the most frequent sensory disorder in humans. Auditory hair cells
(HCs) are postmitotic at late-embryonic differentiation and postnatal stages, and
their damage is the major cause of hearing loss. There is no measurable HC
regeneration in the mammalian cochlea, and the maintenance of cell function is
crucial for preservation of hearing. Here we generated mice deficient in
autophagy-related 5 (Atg5), a gene essential for autophagy, in the HCs to
investigate the effect of basal autophagy on hearing acuity. Deletion of Atg5
resulted in HC degeneration and profound congenital hearing loss. In autophagy
deficient HCs, polyubiquitinated proteins and p62/SQSTM1, an autophagy substrate,
accumulated as inclusion bodies during the first postnatal week, and these
aggregates increased in number. These findings revealed that basal autophagy has
an important role in maintenance of HC morphology and hearing acuity.
PMID- 28492546
TI - Cold-inducible RNA-binding protein through TLR4 signaling induces mitochondrial
DNA fragmentation and regulates macrophage cell death after trauma.
AB - Trauma is a major cause of systemic inflammatory response syndrome and multiple
organ dysfunction syndrome. Macrophages (Mphi) direct trauma-induced
inflammation, and Mphi death critically influences the progression of the
inflammatory response. In the current study, we explored an important role of
trauma in inducing mitochondrial DNA (mtDNA) damage in Mphi and the subsequent
regulation of Mphi death. Using an animal pseudo-fracture trauma model, we
demonstrated that tissue damage induced NADPH oxidase activation and increased
the release of reactive oxygen species via cold-inducible RNA-binding protein
(CIRP)-TLR4-MyD88 signaling. This in turn, activates endonuclease G, which serves
as an executor for the fragmentation of mtDNA in Mphi. We further showed that
fragmented mtDNA triggered both p62-related autophagy and necroptosis in Mphi.
However, autophagy activation also suppressed Mphi necroptosis and pro
inflammatory responses. This study demonstrates a previously unidentified
intracellular regulation of Mphi homeostasis in response to trauma.
PMID- 28492548
TI - Inhibition of PTP1B disrupts cell-cell adhesion and induces anoikis in breast
epithelial cells.
AB - Protein tyrosine phosphatase 1B (PTP1B) is a well-known inhibitor of insulin
signaling pathways and inhibitors against PTP1B are being developed as promising
drug candidates for treatment of obesity. PTP1B has also been linked to breast
cancer both as a tumor suppressor and as an oncogene. Furthermore, PTP1B has been
shown to be a regulator of cell adhesion and migration in normal and cancer
cells. In this study, we analyzed the PTP1B expression in normal breast tissue,
primary breast cells and the breast epithelial cell line D492. In normal breast
tissue and primary breast cells, PTP1B is widely expressed in both epithelial and
stromal cells, with highest expression in myoepithelial cells and fibroblasts.
PTP1B is widely expressed in branching structures generated by D492 when cultured
in 3D reconstituted basement membrane (3D rBM). Inhibition of PTP1B in D492 and
another mammary epithelial cell line HMLE resulted in reduced cell proliferation
and induction of anoikis. These changes were seen when cells were cultured both
in monolayer and in 3D rBM. PTP1B inhibition affected cell attachment, expression
of cell adhesion proteins and actin polymerization. Moreover, epithelial to
mesenchymal transition (EMT) sensitized cells to PTP1B inhibition. A mesenchymal
sublines of D492 and HMLE (D492M and HMLEmes) were more sensitive to PTP1B
inhibition than D492 and HMLE. Reversion of D492M to an epithelial state using
miR-200c-141 restored resistance to detachment induced by PTP1B inhibition. In
conclusion, we have shown that PTP1B is widely expressed in the human breast
gland with highest expression in myoepithelial cells and fibroblasts. Inhibition
of PTP1B in D492 and HMLE affects cell-cell adhesion and induces anoikis-like
effects. Finally, cells with an EMT phenotype are more sensitive to PTP1B
inhibitors making PTP1B a potential candidate for further studies as a target for
drug development in cancer involving the EMT phenotype.
PMID- 28492549
TI - Enhanced neuroprotective efficacy of bone marrow mesenchymal stem cells co
overexpressing BDNF and VEGF in a rat model of cardiac arrest-induced global
cerebral ischemia.
AB - Cardiac arrest-induced global cerebral ischemia injury (CA-GCII) usually leads to
a poor neurological outcome without an effective treatment. Bone marrow-derived
mesenchymal stem cells (BMMSCs) may provide a potential cell-based therapy
against neurologic disorders through induction of brain-derived neurotrophic
factor (BDNF) and vascular endothelial growth factor (VEGF). To optimize the
neuroprotective efficacy of BMMSCs further, in this study we have derived BMMSCs,
which co-overexpress both BDNF and VEGF, and tested them for the treatment of CA
GCII in a rat model. Lentiviruses that express rat BDNF exon IV or VEGF-A were
created using the bicistronic shuttle vectors of pLVX-IRES-ZsGreen1 and pLVX-IRES
tdTomato, respectively. BMMSCs that were co-transduced with the engineered
lentiviruses with co-overexpression of both BDNF and VEGF along with
corresponding fluorescent protein reporters were injected via jugular vein of
rats that just recovered from a cardiac arrest. Animals were then scored for
neurofunctional deficits and examined for brain pathology and gene expression
relevant to the engraftment seven days after the treatments. We demonstrate that
anchorage of lentiviral vector-transduced BMMSCs, which co-overexpressed both
BDNF and VEGF in the hippocampus and temporal cortex along with significantly
ameliorated brain pathology and improved neurofunctional performance in CA-GCII
rats after transplantation. These findings provide a proof of concept for the
further validation of engineered BMMSCs for the treatment of CA-GCII patients in
clinical practice in the future.
PMID- 28492550
TI - TXNIP regulates mitophagy in retinal Muller cells under high-glucose conditions:
implications for diabetic retinopathy.
AB - Thioredoxin-interacting protein (TXNIP) is involved in oxidative stress and
apoptosis in diabetic retinopathy. However, the role of TXNIP in the removal of
damaged mitochondria (MT) via mitophagy, a process of macroautophagy, remains
unexplored. Here we investigate the associated cellular and molecular mechanisms
underlying mitophagy in retinal cells under diabetic conditions. For this, we
maintained a rat Muller cell line (rMC1) under high-glucose (25 mM, HG) or low
glucose (5.5 mM, LG) condition for 5 days. Our data reveal that HG upregulates
TXNIP in the cytosol as well as in the MT. Moreover, mitochondrial oxidative
stress and membrane depolarization occur under prolonged hyperglycemia leading to
fragmentation. These damaged MT are targeted to lysosome for mitophagic
degradation, as is evident by co-localization of mitochondrial protein COXIV, a
subunit of cytochrome c oxidase, with autophagosome marker LC3BII and the
lysosomal membrane protein LAMP2A. In addition, under HG conditions, there is an
accumulation of dynamin-related fission protein Drp1 and E3 ubiquitin ligase
Parkin in damaged MT, suggesting their roles in mitochondrial fragmentation and
ubiquitination, respectively, which is absent in LG conditions. Subsequently,
ubiquitin receptors, optineurin and p62/sequestrome 1, bind to the damaged MT and
target them to LC3BII autophagosomes. Conversely, TXNIP knockout via CRISPR/Cas9
and TXNIP gRNA prevents the HG-induced mitochondrial damage and mitophagy in
rMC1. Last, TXNIP level is also significantly upregulated in the diabetic rat
retina in vivo and induces radial glial fibrillary acidic protein expression, a
marker for Muller glia activation, and the formation of LC3BII puncta, which are
prevented by intravitreal injection of TXNIP siRNA. Therefore, TXNIP represents a
potential target for preventing ocular complications of diabetes.
PMID- 28492552
TI - All-trans retinoic acid and arsenic trioxide fail to derepress the monocytic
differentiation driver Irf8 in acute promyelocytic leukemia cells.
AB - All-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO) administration leads
to granulocytic maturation and/or apoptosis of acute promyelocytic leukemia (APL)
cells mainly by targeting promyelocytic leukemia/retinoic acid receptor alpha
(PML/RARalpha). Yet, ~10-15% of APL patients are not cured by ATRA- and ATO-based
therapies, and a potential failure of ATRA and ATO in completely reversing
PML/RARalpha-driven oncogenic alterations has not been comprehensively examined.
Here we characterized the in vivo primary responses of dysregulated genes in APL
cells treated with ATRA and ATO using a GFP-labeled APL model. Although induced
granulocytic differentiation of APL cells was evident after ATRA or ATO
administration, the expression of the majority of dysregulated genes in the c
Kit+ APL progenitors was not consistently corrected. Irf8, whose expression
increased along with spontaneous differentiation of the APL progenitors in vivo,
represented such a PML/RARalpha-dysregulated gene that was refractory to ATRA/ATO
signaling. Interestingly, Irf8 induction, but not its knockdown, decreased APL
leukemogenic potential through driving monocytic maturation. Thus, we reveal that
certain PML/RARalpha-dysregulated genes that are refractory to ATRA/ATO signaling
are potentially crucial regulators of the immature status and leukemogenic
potential of APL cells, which can be exploited for the development of new
therapeutic strategies for ATRA/ATO-resistant APL cases.
PMID- 28492551
TI - Haploinsufficiency in the mitochondrial protein CHCHD4 reduces brain injury in a
mouse model of neonatal hypoxia-ischemia.
AB - Mitochondria contribute to neonatal hypoxic-ischemic brain injury by releasing
potentially toxic proteins into the cytosol. CHCHD4 is a mitochondrial
intermembrane space protein that plays a major role in the import of
intermembrane proteins and physically interacts with apoptosis-inducing factor
(AIF). The purpose of this study was to investigate the impact of CHCHD4
haploinsufficiency on mitochondrial function and brain injury after cerebral
hypoxia-ischemia (HI) in neonatal mice. CHCHD4+/- and wild-type littermate mouse
pups were subjected to unilateral cerebral HI on postnatal day 9. CHCHD4
haploinsufficiency reduced insult-related AIF and superoxide dismutase 2 release
from the mitochondria and reduced neuronal cell death. The total brain injury
volume was reduced by 21.5% at 3 days and by 31.3% at 4 weeks after HI in
CHCHD4+/- mice. However, CHCHD4 haploinsufficiency had no influence on
mitochondrial biogenesis, fusion, or fission; neural stem cell proliferation; or
neural progenitor cell differentiation. There were no significant changes in the
expression or distribution of p53 protein or p53 pathway-related genes under
physiological conditions or after HI. These results suggest that CHCHD4
haploinsufficiency afforded persistent neuroprotection related to reduced release
of mitochondrial intermembrane space proteins. The CHCHD4-dependent import
pathway might thus be a potential therapeutic target for preventing or treating
neonatal brain injury.
PMID- 28492553
TI - A balance of Mad and Myc expression dictates larval cell apoptosis and adult stem
cell development during Xenopus intestinal metamorphosis.
AB - The Myc/Mad/Max network has long been shown to be an important factor in
regulating cell proliferation, death and differentiation in diverse cell types.
In general, Myc-Max heterodimers activate target gene expression to promote cell
proliferation, although excess of c-Myc can also induce apoptosis. In contrast,
Mad competes against Myc to form Mad-Max heterodimers that bind to the same
target genes to repress their expression and promote differentiation. The role of
the Myc/Mad/Max network during vertebrate development, especially, the so-called
postembryonic development, a period around birth in mammals, is unclear. Using
thyroid hormone (T3)-dependent Xenopus metamorphosis as a model, we show here
that Mad1 is induced by T3 in the intestine during metamorphosis when larval
epithelial cell death and adult epithelial stem cell development take place. More
importantly, we demonstrate that Mad1 is expressed in the larval cells undergoing
apoptosis, whereas c-Myc is expressed in the proliferating adult stem cells
during intestinal metamorphosis, suggesting that Mad1 may have a role in cell
death during development. By using transcription activator-like effector nuclease
mediated gene-editing technology, we have generated Mad1 knockout Xenopus
animals. This has revealed that Mad1 is not essential for embryogenesis or
metamorphosis. On the other hand, consistent with its spatiotemporal expression
profile, Mad1 knockout leads to reduced larval epithelial apoptosis but
surprisingly also results in increased adult stem cell proliferation. These
findings not only reveal a novel role of Mad1 in regulating developmental cell
death but also suggest that a balance of Mad and Myc controls cell fate
determination during adult organ development.
PMID- 28492554
TI - The novel long intergenic noncoding RNA UCC promotes colorectal cancer
progression by sponging miR-143.
AB - The human genome contains thousands of long intergenic noncoding RNAs (lincRNAs).
However, the functional roles of these transcripts and the mechanisms responsible
for their deregulation in colorectal cancer (CRC) remain elusive. A novel lincRNA
termed upregulated in CRC (UCC) was found to be highly expressed in human CRC
tissues and cell lines. UCC levels correlated with lymph node metastasis, Dukes'
stage, and patient outcomes. In SW480 and SW620 cells, knockdown of UCC inhibited
proliferation, invasion, and cell cycle progression and induced apoptosis in
vitro. Xenograft tumors grown from UCC-silenced SW620 cells had smaller mean
volumes and formed more slowly than xenograft tumors grown from control cells.
Inversely, overexpression of UCC in HCT116 promoted cell growth and invasion in
vitro. Bioinformatics analysis, dual-luciferase reporter assays, and RNA
immunoprecipitation assays showed that miR-143 can interact with UCC, and we
found that UCC expression inversely correlates with miR-143 expression in CRC
specimens. Moreover, mechanistic investigations showed that UCC may act as an
endogenous sponge by competing for miR-143, thereby regulating the targets of
this miRNA. Our results suggest that UCC and miR-143 may be promising molecular
targets for CRC therapy.
PMID- 28492555
TI - Acidic pH is essential for maintaining mast cell secretory granule homeostasis.
AB - It has been recognized for a long time that the secretory granules of mast cells
are acidic, but the functional importance of maintaining an acidic pH in the mast
cell granules is not fully understood. Here we addressed this issue by examining
the effects of raising the pH of the mast cell secretory granules. Mast cells
were incubated with bafilomycin A1, an inhibitor of the vacuolar-type ATPase
proton pump. Supporting a role of vacuolar-type ATPase in mast cell granule
acidification, bafilomycin A1 treatment caused a robust increase in granule pH.
This was accompanied by marked effects on mast cell granules, including swelling
and acquisition of vacuole-like morphology. Moreover, bafilomycin A1 caused
extensive, yet selective effects on the granule content. These included aberrant
processing of pro-carboxypeptidase A3 and a reduction in the level of
intracellular histamine, the latter being accompanied by an increase in
extracellular histamine. In contrast, the storage of beta-hexosaminidase, a
prototype lysosomal hydrolase known to be stored in mast cell granules, was not
affected by abrogation of granule acidification. Moreover, bafilomycin A1 caused
a reduction of tryptase enzymatic activity and appearance of tryptase degradation
products. Tryptase inhibition prevented the formation of such degradation
products, suggesting that the pH elevation causes tryptase to undergo
autoproteolysis. Taken together, our findings reveal that mast cell secretory
granule homeostasis is critically dependent on an acidic milieu.
PMID- 28492556
TI - PLSCR1/IP3R1/Ca2+ axis contributes to differentiation of primary AML cells
induced by wogonoside.
AB - Multiple lines of evidence have demonstrated that increased expression of
phospholipid scramblase 1 (PLSCR1) is involved in the differentiation of acute
myeloid leukemia (AML) cells by several differentiation-inducing agents including
ATRA and phorbol 12-myristate 13-acetate. However, none of these agents can
achieve nonhomogenous subcellular distribution of PLSCR1. We have demonstrated
that wogonoside possesses differentiation and anti-leukemic effects in AML cell
lines by promoting PLSCR1 trafficking into nucleus. Here we report that
wogonoside promotes the expression of PLSCR1 and enhances its nuclear
translocation and binding to the 1, 4, 5-trisphosphate receptor 1 (IP3R1)
promoter in AML patient-derived primary cells. Wogonoside activates IP3R1, in
turn, promotes release of Ca2+ from endoplasmic reticulum, and eventually leads
to cell differentiation. Our in vivo study further confirms that wogonoside can
promote PLSCR1 and IP3R1 expression in primary AML cells and reduce the AML cell
counts in engrafted nonobese diabetic/severe combined immunodeficient mice. Taken
together, our findings provide new insight into the mechanism of wogonoside
induced differentiation and anti-leukemic effect on primary AML cells, suggesting
the therapeutic potential of wogonoside for AML, especially for non-APL AML.
PMID- 28492557
TI - Cryptotanshinone inhibits human glioma cell proliferation in vitro and in vivo
through SHP-2-dependent inhibition of STAT3 activation.
AB - Malignant gliomas (MGs) are one of the most common primary brain cancers in
adults with a high mortality rate and relapse rate. Thus, finding better
effective approaches to treat MGs has become very urgent. Here, we studied the
effects of cryptotanshinone (CTS) on MGs in vitro and in vivo, and explored the
underlying mechanisms. Effects of CTS in vitro on cell proliferation, cycle,
migration and invasion were evaluated. The activation of JAK/STATs signaling was
detected by western blot and immunofluorescenc staining. SHP-2 inhibitor or SiRNA
were used to determine the involvement of SHP-2. The in vivo anti-MGs activity of
CTS was studied with nude mice bearing intracerebral U87 xenografts. Our results
revealed that CTS significantly inhibited the proliferation of MGs in vitro via
inhibiting STAT3 signal pathway. The cell cycle was arrested at G0/G1 phase.
Although CTS did not change the expression of total SHP-2 protein, the tyrosine
phosphatase activity of SHP-2 protein was increased by CTS treatment in a dose
dependent manner in vivo and in vitro. SHP-2 inhibitor or SiRNA could reverse the
inhibitory effect of CTS on phosphorylation of STAT3 Tyr705. In vivo study also
showed that CTS inhibited the intracranial tumor growth and extended survival of
nude mice bearing intracerebral U87 xenografts, confirming an inhibitory effect
of CTS on MGs. Our results indicated CTS may be a potential therapeutic agent for
MGs. The inhibitory action of CTS is largely attributed to the inhibition of
STAT3 Tyr705 phosphorylation with a novel mechanism of upregulating the tyrosine
phosphatase activity of SHP-2 protein.
PMID- 28492558
TI - Harnessing combined p19Arf and interferon-beta gene transfer as an inducer of
immunogenic cell death and mediator of cancer immunotherapy.
PMID- 28492559
TI - MK2206 enhances the cytocidal effects of bufalin in multiple myeloma by
inhibiting the AKT/mTOR pathway.
AB - Despite the development of promising cancer therapeutic drugs, multiple myeloma
(MM) remains an incurable disease. Bufalin is a bufanolide steroid compound of
the traditional Chinese medicine Chan Su that was previously shown to exert
growth suppression effects on myeloma cell lines. Previous studies conducted by
our group demonstrated that bufalin activated the AKT/mTOR pathway in myeloma
cells, which is considered an essential pathway to disease progression and is
related to drug resistance in MM. In view of the significant role of AKT in MM,
the allosteric AKT inhibitor MK2206 was selected in order to enhance the
antitumor effects of bufalin in different MM cell lines (NCI-H929, U266, LP-1 and
RPMI8226). The data indicated that MK2206 enhanced the cytotoxicity of bufalin in
MM cells, via the suppression of cellular proliferation and the induction of
apoptosis, as demonstrated by cleavage of apoptosis-related proteins. This effect
was further noted in the presence of exogenous interleukin-6 and/or following the
co-culture of MM cells with bone marrow stromal cells (BMSC). This process was
associated with the inhibition of the AKT/mTOR pathway. The combination of
bufalin with MK2206 reduced the secretion of IL-6 in U266 cells. The combined
treatment exhibited similar anti-MM effects in bortezomib-resistant cell lines
(NCI-H929R, U266R). In addition to the in vitro cell line models, the synergistic
effect was noted in primary MM cells and in MM xenografts of BALB-c and NOD-SCID
mice. In conclusion, the data suggested that MK2206 significantly enhanced the
cytocidal effects of bufalin in MM cells, regardless of the sensitivity to
bortezomib, via the inhibition of the AKT/mTOR pathway. The study provided the
basis of a promising treatment approach for MM.
PMID- 28492561
TI - [Sacubitril/valsartan, a new and effective treatment for heart failure with
reduced ejection fraction].
AB - Despite significant therapeutic advances, patients with chronic heart failure and
reduced ejection fraction (HFrEF) remain at high risk for heart failure
progression and death. The PARADIGM-HF study, the largest outcome trial in HFrEF,
has shown improved cardiovascular outcomes with sacubitril/valsartan
(Entresto(r), Novartis), previously known as LCZ696, compared with angiotensin
converting enzyme (ACE) inhibitor therapy, possibly leading us to a new era for
heart failure treatment. Sacubitril/valsartan represents a first-in-class drug
acting through inhibition of angiotensin receptor and neprilysin, thus modulating
the renin-angiotensin-aldosterone system and vasoactive substances such as
natriuretic peptides. This approach can be considered a "paradigm shift" from
neurohumoral inhibition to neurohumoral modulation. Based on the PARADIGM-HF
results, the European Society of Cardiology and the American Heart
Association/American College of Cardiology guidelines proposed a substitution of
ACE-inhibitor/angiotensin receptor blocker therapy rather than an "add-on"
strategy in HFrEF. Sacubitril/valsartan can be considered a milestone in
cardiovascular therapy, like aspirin, statins, beta-blockers. Of course there are
many questions that arise spontaneously from this trial, three recognized experts
can help us to answer them.
PMID- 28492560
TI - miR-218-5p restores sensitivity to gemcitabine through PRKCE/MDR1 axis in
gallbladder cancer.
AB - Gallbladder cancer (GBC) is one of the most common malignancy of the biliary
tract characterized by its high chemoresistant tendency. Although great
progresses have been made in recent decades for treating many cancers with
anticancer drugs, effective therapeutics methods for anti-GBC are still lacking.
Therefore, investigations into identifying the mechanisms underlying the drug
resistance of GBC are greatly needed. In this study, we show that miR-218-5p
plays a critical role in gemcitabine resistance of GBC. miR-218-5p levels were
significantly lower in GBC than adjacent non-cancer tissues, and which were also
associated with patient prognosis. While miR-218-5p overexpression abrogated
gemcitabine resistance of GBC cells, silencing of which exhibited the opposite
effects. Via six microRNA targets prediction algorithms, we found that PRKCE is a
potential target of miR-218-5p. Moreover, miR-218-5p overexpression repressed the
luciferase activity of reporter constructs containing 3'-UTR of PRKCE and also
reduced PRKCE expression. Further studies revealed that miR-218-5p promotes
sensitivity of gemcitabine by abolishing PRKCE-induced upregulation of MDR1/P-gp.
Taken together, our results imply that an intimate correlation between miR-218-5p
and PRKCE/MDR1 axis abnormal expression is a key determinant of gemcitabine
tolerance, and suggest a novel miR-218-5p-based clinical intervention target for
GBC patients.
PMID- 28492563
TI - [Follow-up strategies after percutaneous coronary intervention: prognostic
stratification and multidisciplinary management based on patient risk profile].
AB - The number of percutaneous coronary interventions (PCI) is increasing worldwide.
Follow-up strategies after PCI are extremely heterogeneous and can greatly affect
the cost of medical care. In the present paper, practical advises are provided
with respect to a tailored follow-up strategy on the basis of patients' risk
profile. Clinical and interventional cardiologists, cardiac rehabilitators, and
general practitioners equally contributed to the creation of the present document
and defined three follow-up strategies and types and timing of clinical and
instrumental evaluations in post-PCI patients.
PMID- 28492564
TI - [Heart rate as a therapeutic target after acute coronary syndrome and in chronic
coronary heart disease].
AB - For patients with stable coronary artery disease (SCAD), either after
hospitalization for acute cardiac events or in the chronic phase, comprehensive
treatment programs should be devoted to: (i) reducing mortality and major adverse
cardiovascular events, (ii) reducing the ischemic burden and related symptoms,
and (iii) increasing exercise capacity and quality of life.Heart rate (HR) has
demonstrated to have prognostic value and patients beyond the limit of 70 bpm
display increased risk of all the above adverse outcomes, even after adjustment
for parameters such as the extension of myocardial infarction and the presence of
heart failure. It is well known that a sustained HR elevation may contribute to
the pathogenesis of SCAD, being the likelihood of developing ischemia, plaque
instability, trigger for arrhythmias, increased vascular oxidative stress, and
endothelial dysfunction the mechanisms resulting in this effect. Moreover, high
HR could promote chronotropic incompetence, leading to functional disability and
reduced quality of life.Despite the strong relationship between HR and prognosis,
there is heterogeneity among current guidelines in considering HR as a formal
therapeutic target for secondary prevention in SCAD, as far as the cut-off limit.
This expert opinion document considered major trials and observational registries
in the modern treatment era with beta-blockers and ivabradine, suggesting that an
adequate HR control could represent a target for (i), (ii), and (iii) therapeutic
goals in SCAD patients with systolic dysfunction (with major evidence for reduced
left ventricular ejection fraction <40%), and a target for (ii) and (iii) goals
in SCAD patients with preserved left ventricular ejection fraction. The defined
cut-off limit is 70 bpm. To date, there is room for improvement of HR control,
since in contemporary SCAD patients HR values <70 bpm are present in less than
half of cases, even in the vulnerable phase after an acute coronary syndrome.
PMID- 28492565
TI - ?
PMID- 28492566
TI - [Speckle tracking echocardiography: a practical guide].
AB - Speckle tracking echocardiography (STE) has recently emerged as a quantitative
technique to accurately estimate myocardial function. By the analysis of the
motion of speckles in the two-dimensional ultrasonic image, this technique allows
a non-Doppler angle-independent objective analysis of myocardial deformation,
with the possibility to quantify thickening, shortening and rotation dynamics of
cardiac function. Since this technique does not require Doppler imaging, the
analysis is relatively angle-independent and is marginally affected by cardiac in
plane motion artifacts. Data regarding feasibility, reproducibility and
diagnostic accuracy appear to be optimal in several clinical contexts. This
review describes the fundamental concepts of deformation imaging, explains how to
obtain myocardial deformation measurements in clinical practice and highlights
current clinical applications of STE. In addition, in relation with the recent
extension of STE to three-dimensional echocardiography with the potential for a
more comprehensive analysis of global and segmental myocardial function, a window
is also opened on the perspectives of three-dimensional STE.
PMID- 28492567
TI - [Echocardiographic assessment of mitral regurgitation in the perspective of valve
repair].
AB - Echocardiography is the most used imaging technique for the study of patients
with mitral regurgitation because of its wide distribution, non-invasiveness and
ability to provide diagnostic, functional, hemodynamic and prognostic
evaluations. Also, echocardiography can provide essential information on surgical
and percutaneous reparability of the regurgitant valve and can guide the surgical
and interventional indications relative to valve repair. However, the
echocardiographic study is not always appropriately performed in clinical
practice and based on a surgery perspective. Therefore, the purpose of this
article is to describe how to best use echocardiography for evaluation of
patients with mitral regurgitation, highlighting the advantages and limitations
of this technique before and after surgical or interventional repair.
PMID- 28492569
TI - [Electromagnetic interference in the current era of cardiac implantable
electronic devices designed for magnetic resonance environment].
AB - In the last decades we are observing a continuous increase in the number of
patients wearing cardiac implantable electronic devices (CIEDs). At the same
time, we face daily with a domestic and public environment featured more and more
by the presence and the utilization of new emitters and finally, more medical
procedures are based on electromagnetic fields as well. Therefore, the topic of
the interaction of devices with electromagnetic interference (EMI) is
increasingly a real and actual problem.In the medical environment most attention
is paid to magnetic resonance, nevertheless the risk of interaction is present
also with ionizing radiation, electrical nerve stimulation and electrosurgery. In
the non-medical environment, most studies reported in the literature focused on
mobile phones, metal detectors, as well as on headphones or digital players as
potential EMI sources, but many other instruments and tools may be intentional or
non-intentional sources of electromagnetic fields.CIED manufacturers are more and
more focusing on new technological features in order to make implantable devices
less susceptible to EMI. However, patients and emitter manufacturers should be
aware that limitations exist and that there is not complete immunity to EMI.
PMID- 28492568
TI - [Cardiac tumors: role of magnetic resonance imaging].
AB - The incidental finding of a cardiac or paracardiac mass constitutes for
cardiologists a relevant diagnostic and therapeutic problem. In fact, although
primary cardiac tumors are infrequently, metastases, as well as non-neoplastic
masses and pseudomasses, are much more frequent. A key role is played by
echocardiography, but the latter is not always nullifying. Sometimes even the
currently used imaging techniques may be limited in oncology. Cardiac magnetic
resonance (CMR) is a multi-parametric technique of imaging considered nowadays
the gold standard for non-invasive soft tissue characterization. CMR allows (i)
to better evaluate the relationship between the tumor and adjacent structures,
(ii) to detect the degree of infiltration or the expansion of the mass in the
pericardium, and (iii) to predict the possible malignancy of a mass with a higher
accuracy than other methods. In addition, CMR can favor the choice of the
technique for surgical resection by providing information regarding cardiac
function and the possible hemodynamic impairment. In this regard, we here present
a narrative review on the most frequent cardiac manifestations of tumors, masses
and pseudomasses, as well as the currently used CMR techniques in this setting.
PMID- 28492570
TI - [The use of mechanical chest compression devices for both out-of-hospital and in
hospital refractory cardiac arrest].
AB - The purpose of cardiopulmonary resuscitation after sudden cardiac arrest is to
restore minimal blood flow to provide oxygen to the brain and other vital organs.
Chest compressions and external defibrillation are the first line for circulatory
support. Although early defibrillation is the main factor influencing survival,
cardiopulmonary resuscitation must be characterized by high-quality external
chest compressions. Unfortunately, the performance of manual chest compressions
decreases during time and in hostile conditions. For these reasons, mechanical
devices for chest compression are able to support rescuers during cardiopulmonary
resuscitation. Commonly used mechanical chest compression devices in Europe
include LUCAS and Autopulse. Routine utilization of mechanical chest compression
devices cannot be recommended because randomized controlled trials, such as LINC
and PARAMEDIC for LUCAS and CIRC for Autopulse, have not demonstrated their
superiority compared with manual chest compressions. The aim of this review is to
analyze recent data regarding utilization of mechanical chest compression
devices, and to clarify advantages and limitations.
PMID- 28492571
TI - [Teamwork for cardiac imaging: coronary computed tomography angiography and low
dose radiation exposure: a cardiology center experience].
AB - BACKGROUND: Multidetector coronary computed tomography angiography (CCTA) is
increasingly used for noninvasive imaging of the coronary arteries. Radiation
exposure, however, is a potential limitation to a more extensive use of this
imaging modality. We aimed to demonstrate that a professional teamwork approach,
including a cardiologist and a radiologist in performing CCTA, may allow to
obtain best quality exams with very low radiation doses. METHODS: A total of 998
consecutive patients underwent CCTA in accordance with the most recent
guidelines. The following procedures were undertaken to reduce the radiation
dose: (a) preliminary cardiological evaluation to check for CCTA eligibility; (b)
optimized heart rate control with beta-blockers and/or ivabradine; and (c) the
use of nonstandardized computed tomography protocols and algorithms for dose
reduction. RESULTS: All the patients underwent a preliminary cardiological
evaluation; 89% of them were pretreated with oral or intravenous beta-blockers
and/or ivabradine; 806 patients (81%) were scanned by means of prospective
gating, which allowed a radiation dose exposure of 161 +/- 68.64 mGy; 192
patients (19%) underwent a retrospective gating protocol, with a radiation dose
exposure of 1135.15 +/- 485.87 mGy. In 13 patients (1%) CCTA was uninterpretable
because of artifacts. Exam quality was not affected by the use of low-dose
computed tomography scanning. Coronary calcium score and/or left ventricular
functional analysis were never performed. CONCLUSIONS: The preliminary selection
and preparation of patients and optimized scanner utilization allow a substantial
reduction in radiation dose for most of the patients submitted to CCTA without
affecting image quality. In our experience, a team approach was necessary to
allow a "low-dose learning curve" and a progressive reduction in radiation doses
administered to patients by means of the prospective gating protocol.
PMID- 28492572
TI - [The spiral of evil: iatrogenic coronary and aortic dissection].
AB - Iatrogenic coronary and aortic dissection is one of the worst complication during
a percutaneous coronary intervention. Nevertheless, it can be approached and
effectively resolved by a percutaneous way, sealing the false lumen "entry door"
with a covered stent, even if this device is more thrombogenic than other bare
metal or drug-eluting stents. We report the case of a 60-year-old man with acute
ST-elevation myocardial infarction complicated by both iatrogenic dissection and
multiple stent thrombosis.
PMID- 28492573
TI - [Lotus Sadra valve implantation complicated by type B aortic dissection:
diagnosis and treatment].
AB - Transcatheter aortic valve implantation (TAVI) is a validated technique for the
treatment of aortic valve stenosis in patients with high surgical risk or
inoperable. We present the case of an 80-year-old woman with severe aortic valve
stenosis (mean gradient 55 mmHg), mild surgical risk, who refused traditional
surgery. We implanted a Lotus Sadra 25 mm (Boston Scientific, Marlborough, MA,
USA) via the transfemoral route. During pull back delivery, the patient
experienced interscapular pain with angiographic evidence of type B aortic
dissection effectively treated by implanting a vascular endoprosthesis Valiant 30
x 150 mm (Medtronic Vascular, Santa Rosa, CA, USA). Type B aortic dissection is a
rare event during TAVI. The onset of procedural complications, often
unpredictable, suggests the need for more extensive knowledge of materials and
techniques, in particular with respect to endovascular treatment of the aortic
and iliac-femoral district.
PMID- 28492574
TI - [Magnetic resonance detection of direct ascending aorta invasion by lung cancer].
PMID- 28492575
TI - Alterations of cerebral white matter structure in psychosis and their clinical
correlations: a systematic review of Diffusion TensorImaging studies.
AB - Schizophrenia is a common, severe and chronically disabling mental illness. Most
of MRI studies in schizophrenia suggest theinvolvement of white matter (WM)
pathology in multiple cerebral regions in the neurobiology of this condition.
White matter fiber tracts connecting numerous cortical regions have been the
focus of a number of studies using a magnetic resonance technique called
"Diffusion Tensor Imaging" (DTI). A literature search of published DTI studies
was conducted using the major database National Centre for Biotechnology
information (NCBI) PubMed (MEDLINE). Our review covers 95 published papers. We
summarise the main DTI findings involving the different brain regions in patients
affected by or at high-risk for psychosis; we discuss clinical implications of
these white matter disruptions and the limitations of current studies, listing
the potential confounds and suggesting potential future research directions.
PMID- 28492576
TI - [Mental capacity and capacity to consent: multicentric study in a involuntary
psychiatric hospitalized patients sample].
AB - BACKGROUND: The purpose of this longitudinal observational study is to evaluate
the course and impact of clinical, social, and behavioral variables on the
involuntary readmission of psychiatric patients, during a 6-months follow-up
after discharge from a prior involuntary hospitalization. METHODS: N=131
involuntarily committed psychiatric patients were enrolled in three university
hospitals (Bari n=57; Perugia n=42; Rome n=32). At the first assessment cognitive
functioning (MMSE), psychiatric symptoms severity (BPRS-E), capacity to consent
to treatment (MacCAT-T) as well as principal socio-demographic and clinical
variables were collected. At 6-months follow-up, we collected data concerning
involuntary psychiatric readmissions, pharmacotherapy adherence, new deliberate
self-harm or harm to others as well as having been legally prosecuted. RESULTS:
N=120 patients were reevaluated at follow-up (M=188 days, SD=12.6); among these
n=15 (12.5%) have had a new involuntary psychiatric admission due to an acute
mental disorder. Re-hospitalized patients showed higher rates of harm to others
(p<0.05) and legal prosecution (p<0.05); there was moreover a trend toward higher
pharmacological dropout rates in involuntarily rehospitalized patients. We found
no differences between the two groups in baseline psychiatric symptoms severity
and cognitive functioning, whereas involuntary re-hospitalization was associated
with more frequent involuntary hospitalization during last year (p<0.05) and
higher MacCAT-T reasoning (p<0.05). CONCLUSIONS: Involuntary psychiatric
readmission rates proved to be poorly associated with clinical features assessed
during previous hospitalization. Our data suggest that social and legal factors,
including those connected to patients' dangerousness, could play a role also in a
civil commitment system based solely on the need for treatment.
PMID- 28492577
TI - [Neuropsychological profiles, personality features and familial relational
patterns in parents of children with Autism Spectrum Disorders].
AB - INTRODUCTION: The study of neuropsychological profiles and personality features
of parents of persons with Autism Spectrum Disorder (ASD) has highlighted
specific traits that turned out to be useful for diagnostic purposes. AIM AND
METHODS: In our study, psychodiagnostic measures have been used to investigate
cognitive profiles, personality features and familial relational patters in a
group of parents of children with ASD associated to Intellectual Disability (ID).
This group was then compared with a another group of parents of children with
Prader-Willi syndrome. RESULTS: Results show no differences between the two
groups with regard to Intellectual Quotient, while significant differences were
found at the intelligence test Wechsler, which partially confirmed data from the
literature relating to the performances of parents of persons with ASD. No
differences were found in the executive functioning and memory abilities. As for
familial relational patters, families of children with ASD showed decreased
cohesion and higher disengagement. DISCUSSION AND CONCLUSIONS: Results obtained
in the domains of familial relational patterns and emotional personality
components seem to confirm how children's disability can significantly impact on
the entire household, in particular in the case of children with ASD. This data
suggest the need for intervention programs aimed at supporting the entire
household, with the objective of improving coping strategies and resilience
resources of the family.
PMID- 28492578
TI - Implicit affectivity in patients with borderline personality disorder.
AB - AIMS: It has been argued that borderline personality disorder (BPD) is related to
an enhanced affective reactivity. According to findings from research based on
self-report, individuals with BPD develop and feel more negative and less
positive affect than healthy individuals. Implicit affectivity, which can be
measured using indirect assessment methods, relates to processes of the
impulsive, intuitive system. In the present study, implicit and explicit
affectivity was examined in patients suffering from BPD compared to healthy
persons. MATERIALS AND METHODS: Thirty-five women with BPD and 35 healthy women
participated in the study. Implicit affectivity was assessed using the Implicit
Positive and Negative Affect Test (IPANAT). Measures of explicit state and trait
affectivity were also administered. RESULTS: BPD women had lower explicit
positive state and trait affect scores and higher negative state and trait affect
scores than healthy women. They had also lower implicit positive affect but they
did not differ from healthy women regarding implicit negative affect. Total
number of comorbiddisorders was correlated with both implicit positive and
implicit negative affect. DISCUSSION AND CONCLUSIONS: According to our data, BPD
patients exhibit reduced implicit positive affect as well as reduced explicit
positive affect compared to healthy persons. According to our IPANAT data, BPD
patients are characterized by a normal disposition to develop negative affective
reactions which is in line with a number of findings from psycho-physiological
research on BPD. Self-reports of negative affectivity in BPD could be biased by
negative distortion.
PMID- 28492579
TI - Prevalence and factors associated with problematic internet use: an Italian
survey among L'Aquila students.
AB - AIM: In this study we examined the prevalence of internet addiction (IA) and its
associated factors in a sample of Italian students. MATERIALS AND METHODS: This
is an observational study that involved 1403 students aged 15-24 and conducted in
L'Aquila, Italy. 1129 students accepted to participate in our study and completed
the Internet Addiction Test: 41% were male and the mean age of total sample was
19+/-2.8 years. RESULTS: The prevalence of "average user" was 51% (95% CI: 48
54). The prevalence of "problematic user" was 23% (95% CI: 21-26). Among the
students with a problematic use, 8 were addicted, the 0.7% in the whole sample.
There was a significant age difference (p=0.029), but no gender difference
(p=0.311) between "average users" and "problematic users". The association of
internet use and educational level (School or University) was not significant
(p=0.704). DISCUSSION: Our results showed that about one student out of 100 had
an IA. Gender and educational level were not significantly associated with IA.
Instead, we found a strong association with age: there was not a decrease of
internet use during a lifetime, with negative consequences on quality of life.
CONCLUSION: Our study reported a percentage of 30% of problematic internet use
among students. These findings suggest the importance of early detection among
youth and of structured interventions that should be carried out to prevent
abnormal global life functioning.
PMID- 28492583
TI - [Adherence to long-term therapies and its relevance to epidemiology.]
AB - In Italy, 40% of the population is affected by chronic pathologies, like
diabetes, chronic obstructive pulmonary disease (COPD) or heart failure. Chronic
diseases are the leading cause of mortality in the world. Although long-term
medications are effective, approximately 50% of patients do not take their
medications as prescribed. The lack of medication adherence is associated with an
increased risk of hospitalization and death. According to recent research, the
low adherence to treatment is a multidimensional problem determined by the
interaction of patient-related factors, physician-related factors and health
system-related factors. In a study of about 10,000 patients, after a hospital
discharge for myocardial infarction, only 63% of patients were adherent to poly
therapy in the following two years. The probability of adherence was influenced
by disease severity, therapy-related factors, patient's age and comorbidities,
post-hospital follow-up visits, and network organizational forms in primary care.
Moreover, a relevant variation in adherence to treatment was observed among
health care providers. This heterogeneity raises equity concerns in access to
optimal care.
PMID- 28492584
TI - [Community pharmacy; towards a new model.]
AB - In recent years, even in Italy, a new model of "Community pharmacy" is being
developed, which identifies the pharmacist as the most accessible health care
professional for citizens, and recognizes his role in preventing chronic
diseases. A project started in Piedmont (Italy) in 2012 has aimed at applying and
evaluating this model of pharmacy in the prevention of diabetes, through the
early detection of individuals with undiagnosed diabetes or at high risk of
developing the disease, or with counselling to diabetic patients not adhering to
the optimal therapeutic pathway. The results suggest that the pharmacy might be
able to implement an effective preventive action, particularly among socio
economically disadvantaged people, thereby helping to reduce inequalities in
care. The cost/effectiveness evaluation of long-term outcomes, based on the use
of existing health information systems, will provide more accurate information on
the value of the model.
PMID- 28492585
TI - Biosimilars in oncology: everybody agrees but nobody uses?
AB - Reducing the cost of biologics is an important avenue for addressing financial
toxicity in oncology, one of the biggest challenges for health systems. The use
of biosimilars, the cheaper alternatives to biologics, is an important strategy
to that end. But the enthusiasm of developing biosimilars is meaningless if they
get to the market, but they're not prescribed by the physicians, concerned by
unexpected side effects or inferior efficacy. A recent study found no differences
between biosimilars and erythropoietin stimulating agents originators in the
composite outcome including all-cause mortality, blood transfusion and major
cardiovascular events. Such studies are important to allay the concerns of
physicians and patients regarding the use of biosimilars. Physician and patient
education, backed by clinical guidelines and patient advocacy groups, are the
keys to improving the uptake ofbiosimilars in clinical practice.
PMID- 28492586
TI - [Risk of pneumonia during long term regular treatment of stable COPD with inhaled
glucocorticoids: a systematic review.]
AB - Inhaled glucocorticoids are anti-inflammatory drugs used in combination with long
acting bronchodilators beta2-agonists for the treatment of stable chronic
obstructive pulmonary disease (COPD), to improve lung function and symptoms and
to reduce the future risk COPD exacerbations. However, has been also associated
to an increased risk of pneumonia. The objective of this systematic review was
therefore to analyze all randomized controlled trials to identify the risk of
pneumonia during the regular treatment with long-term inhaled
glucocorticosteroids compared to treatment with placebo in patients with stable
COPD. From a literature search on PubMed, 19 randomized, placebo-controlled, long
term (at least 52-week) studies have been identified. The inhaled glucocorticoids
administered were: budesonide (6 studies), mometasone furoate (3 studies),
beclomethasone dipropionate (1 study), triamcinolone acetonide (1 study),
fluticasone propionate (7 studies) and fluticasone furoate (1 study). Only 7 of
the 19 trials identified in our systematic review reported data on pneumonia and
only one study required radiological evidence for diagnosis. The incidence of
pneumonia was slightly increased in patients treated with glucocorticoid inhaled
compared to placebo in most studies, regardless of the type of glucocorticoid
inhalation used, suggesting a class effect. Older age, low body mass index, low
FEV1, being a smoker are all factors variously associated with increased risk of
pneumonia.
PMID- 28492587
TI - [Intentional roundings in general medical practice: the experience of the Azienda
Ospedali Riuniti Marche Nord (Italy).]
AB - INTRODUCTION: The "intentional roundings" are planned rounds, conducted at
regular intervals by nursing staff to anticipate care, comfort, hospitality and
psychological needs of hospitalized users. These purposes are achieved with a
structured way to make observations and carry out activities for well-being and
patient safety, documenting what was done with a structured ad hoc form. In the
United Kingdom, as well as in the USA, intentional rounding is an established
model of care that improve the safety of provided care, to reduce the occurrence
of preventable events, address proactively basic caring needs, and that increase
users and staff satisfaction. OBJECTIVE: Implementing in a medical pilot unit the
care model named "intentional rounding". METHODS: The care team carried
intentional rounds every two hours, in a systematic and documented manner. All
patients received admission informations about the organizational method and were
invited to participate by completing a satisfaction questionnaire at discharge.
At the end of the experimental period organizational impact have been
investigated, specifically users and hospital staff satisfaction. RESULTS: About
privacy, courtesy, nurse support and quality of care provided, level of
satisfaction of patients and caregivers reached high percentage of approval (90
99%). Nurses and other healthcare personnel have perceived they delivered either
a safer and most satisfying healthcare (90-94%) as well as inter- and intra
professional dynamics communications (95%). Value of roundings have been less
appreciated concerning the optimization about the worktime management (79%).
Calls to the bell have had a notable change of their reasons unlikely about the
quantity. CONCLUSIONS: Intentional roundings affects very positively to users
satisfaction level and to the perception of the quality of care provided; the
care team, though express the need to make some changes for a real
implementation, recognize the proactivity of intentional roundings as an added
value.
PMID- 28492588
TI - [A rare case of intussusception in a seventeen year old boy: diagnosis,
management and review of the literature.]
AB - Intussusception is the most common cause of intestinal obstruction and acute
abdomen in the first year of life. Approximately in the 80% of cases
intussusception occurs when the last ileal loop is pulled into the cecum, passing
through the ileocecal valve, and finally resulting in the displacement of cecum
in the upper abdominal. It could be related with mesenteric adenitis because
enlarged lymph nodes, together with peristalsis, can serve as "lead point". Other
forms of intussusception are ileo-ileal and colo-colic. The aetiology in infants
and adults can be very variable and most often linked with secondary causes, such
as benign or malignant lesions (polyps, tumors, lymphomas, intestinal duplication
cyst, Meckel's diverticulum). In this paper we describe a rare case of idiopathic
ileo-ileal intussusception in a 17 year old boy. We also discuss, with a careful
analysis of the literature, the diagnostic and therapeutic protocol in case of
intussusception ileo-colic approved at the Meyer Children's Hospital.
PMID- 28492590
TI - ?
PMID- 28492589
TI - [Marcato aumento delle concentrazioni di procalcitonina dopo idroclorotiazide
edema polmonare indotta.]
AB - INTRODUCTION: In the Medline database there are approximately 60 cases reporting
toxic pulmonary edema, a life-threatening event, induced after consumption of
hydrochlorothiazide, one of the most common antihypertensive drugs. Moreover,
increased procalcitonin concentrations have been reported after cardiogenic
pulmonary edema. We report the rare case of a hydrochlorothiazide-induced
pulmonary edema, which was followed by a marked increase of the procalcitonin
concentrations. CLINICAL CASE: A middle-aged woman was admitted to the Emergency
Department for severe dyspnea and chills. Such symptoms began 30 minutes after
consumption of hydrochlorothiazide. Her physical examination and chest-X-ray were
compatible with pulmonary edema, however her brain natriuretic peptide levels and
echocardiogram were almost normal. Interestingly she had extremely elevated
procalcitonin concentrations with normal white blood cells count and C-reactive
protein levels only mildly increased. We hypothesized toxic pulmonary edema and
started treatment with non-invasive mechanical ventilation, with the patient
presenting rapid clinical improvement. CONCLUSIONS: Even if extremely rare,
hydrochlorothiazide may induce pulmonary edema; significant increase of
procalcitonin concentrations may occur in this condition and perhaps in other
cases of toxic pulmonary edema. Practitioners should be aware of this condition
in order to spare expensive and useless, in this case, investigations such as
blood cultures and treatments (antibiotics) if other signs of infection are
absent.
PMID- 28492591
TI - ?
PMID- 28492592
TI - Electronic collaboration in dermatology resident training through social
networking.
AB - The use of online educational resources and professional social networking sites
is increasing. The field of dermatology is currently under-utilizing online
social networking as a means of professional collaboration and sharing of
training materials. In this study, we sought to assess the current structure of
and satisfaction with dermatology resident education and gauge interest for a
professional social networking site for educational collaboration. Two surveys
one for residents and one for faculty-were electronically distributed via the
American Society for Dermatologic Surgery and Association of Professors of
Dermatology (APD) listserves. The surveys confirmed that there is interest among
dermatology residents and faculty in a dermatology professional networking site
with the goal to enhance educational collaboration.
PMID- 28492593
TI - Eruptive melanocytic nevi during azathioprine therapy for antisynthetase
syndrome.
AB - Eruptive melanocytic nevi (EMN) are rare multiple benign melanocytic nevi that
develop within a few months. The phenomenon has been associated with a variety of
dermatologic and systemic conditions, including Stevens-Johnson syndrome, toxic
epidermal necrolysis, epidermolysis bullosa, Addison disease, human
immunodeficiency virus infection, and internal malignancy, among others. It also
is commonly attributed to medications, particularly immunosuppressive and
chemotherapeutic agents. We report a case of EMN in a 50-year-old man undergoing
azathioprine therapy for antisynthetase syndrome.
PMID- 28492594
TI - Improving patient satisfaction in dermatology: a prospective study of an urban
dermatology clinic.
AB - Patient satisfaction has become an important measure of quality under the Patient
Protection and Affordable Care Act. In this study, we assessed and analyzed
patient satisfaction, nonattendance rates, and cycle times in an outpatient
dermatology clinic. This study provides a snapshot of patient satisfaction in an
urban dermatology clinic. Under the Patient Protection and Affordable Care Act,
providers will be challenged to increase access to care and to validate quality
of care through patient satisfaction.
PMID- 28492595
TI - LGBT access to health care: a dermatologist's role in building a therapeutic
relationship.
PMID- 28492596
TI - Large hyperpigmented plaques on the trunk of a newborn.
PMID- 28492597
TI - Pruritic rash on the buttock.
PMID- 28492598
TI - Microneedling therapy with and without platelet-rich plasma.
AB - Microneedling therapy is an increasingly popular treatment of several
dermatologic conditions. Platelet-rich plasma (PRP) may serve as a valuable
adjunct to improve the regenerative effects of treatment. We review the evidence
comparing the results of microneedling therapy with and without PRP. Based on the
current preliminary literature, PRP appears to augment the cosmetic outcomes of
microneedling without increasing the risk for adverse events.
PMID- 28492599
TI - Allergic reaction to vanadium causes a diffuse eczematous eruption and titanium
alloy orthopedic implant failure.
AB - Allergy as a cause of adverse outcomes in patients with implanted orthopedic
hardware is controversial. Allergy to titanium-based implants has not been well
researched, as titanium is traditionally thought to be inert. We highlight the
case of a patient who developed systemic dermatitis and implant failure after
surgical placement of a titanium alloy (Ti6Al4V) plate in the left foot. The
hardware was removed and the eruption cleared in the following weeks. The plate
and screws were submitted for metal analysis. The elemental composition of both
the plate and screws included 3 major elements-titanium, aluminum, and vanadium
as well as trace elements. Metal analysis revealed that the plate and screws had
different microstructures, and electrochemical studies demonstrated that galvanic
corrosion could have occurred between the plate and screws due to their different
microstructures, contributing to the release of vanadium in vivo. The patient was
patch tested with several metals including components of the implant and had a
positive patch test reaction only to vanadium trichloride. These findings support
a diagnosis of vanadium allergy and suggests that clinicians should consider
including vanadium when patch testing patients with a suspected allergic reaction
to vanadium-containing implants.
PMID- 28492600
TI - Efinaconazole solution 10% for treatment of toenail onychomycosis in Latino
patients.
AB - Onychomycosis is a common progressive fungal infection of the nail bed, matrix,
or plate leading to destruction and deformity of the toenails and fingernails.
The prevalence of onychomycosis is increasing in the United States, particularly
in the growing population of Latino patients. In this study, we evaluated the
efficacy and safety of efinaconazole solution 10% in Latino patients with
onychomycosis. Once-daily application of efinaconazole solution 10% may be an
effective topical option for treatment of onychomycosis in this patient
population.
PMID- 28492601
TI - Flesh-colored nodule with underlying sclerotic plaque.
PMID- 28492602
TI - Redness and painful ulcerations in the perineal area.
PMID- 28492603
TI - Recovery of hair in the psoriatic plaques of a patient with coexistent alopecia
universalis.
PMID- 28492604
TI - Serpentine supravenous hyperpigmentation following cisplatin and pemetrexed
chemotherapy.
PMID- 28492605
TI - Severe refractory atopic dermatitis with elevated serum IgE treated with
omalizumab.
PMID- 28492606
TI - Expanding uses of propranolol in dermatology.
AB - Propranolol as a dermatologic therapeutic tool was first described in 2008. Since
then, propranolol has had a pivotal role in the dermatology arena for a myriad of
cutaneous disorders. This article highlights the timeline of the incorporation of
propranolol as a treatment option for a number of vascular lesions.
PMID- 28492607
TI - Blepharoplasty markers: comparison of ink drying time and ink spread.
AB - Marking of the eyelid is a crucial presurgical step in blepharoplasty. A number
of markers are available for this purpose with variable ink characteristics. In
this study, we measured the ink drying time and spread width of 13 markers used
for preoperative marking for blepharoplasty. Based on the results, we propose
markers that may be best suited for use in this procedure.
PMID- 28492608
TI - Sinonasal symptom-related sleep disorders before and after surgery for nasal
polyposis.
AB - BACKGROUND: Patients with nasal polyposis (NP) complain of several sinonasal
symptoms that impact their sleep and quality of life. However, data on sleep
disorders related to NP symptoms, before and after surgery, is poor. The aim of
the present study was to analyze sleep complaints related to each NP symptom,
before and after surgery, using the Dynachron questionnaire. METHODOLOGY: 63
patients operated for NP were included in this prospective study. They filled the
DyNaChron questionnaire one day before surgery (V0), 6 weeks (V1) and 7 months
(V2) after surgery. The self-ratings (0-10 point visual analog scale) of nasal
obstruction, anterior rhinorrhea, postnasal discharge, cough and 5 items related
to sleep disturbances, due to each symptom of chronic nasal dysfunction, were
extracted from the questionnaire and analyzed. RESULTS: There was significant
improvement of symptoms and symptom-related sleep disturbance scores at V1 and V2
compared to baseline scores. Before surgery, moderate/severe sleep disorders that
patients attributed to nasal obstruction (the patient thinks it is due to nasal
obstruction rather than a clinical test to show nasal obstruction) or anterior
rhinorrhea were reported in two thirds of patients, postnasal discharge in one
half, and chronic cough in one third. After surgery, less than 10% of patients
reported moderate/severe sleep disorders at V1. There was a mild increase of
patients who rated moderate/severe sleep disorders at V2 in comparison to V1. The
correlation between scores of nasal obstruction and its impacts on sleep quality
was weak before surgery and strong afterwards. CONCLUSION: Nasalization improved
sleep quality significantly at 6 weeks and at 7 months after surgery. However,
there was a mild increase of complaints related to postnasal discharge and cough
at 7 months after surgery.
PMID- 28492609
TI - The risk of osteoporosis in oral steroid treatment for nasal polyposis: a
systematic review.
AB - BACKGROUND: Systemic glucocorticoids are often used in the treatment of chronic
rhinosinusitis with nasal polyps (CRSwNP), and osteoporosis is a well-known
complication to steroid treatment, associated with significant morbidity.
Nevertheless, the burden of steroid induced osteoporosis is unknown in patients
with CRSwNP. We aimed to assess the risk of acquiring osteoporosis caused by oral
steroids in patients with CRSwNP, and provide recommendations on future research
and guidelines. METHODOLOGY: Cochrane Review Database, EMBASE, Ovid Medline, and
PubMed were searched for studies including adult patients with CRSwNP treated
with oral steroids. Outcomes were Bone Mineral Density (BMD) and prevalence of
fractures in relation to dose and duration of oral steroids. In addition, we
reviewed general guidelines for treatment with oral steroids. RESULTS: We
identified two studies (n=243) that met the inclusion criteria. Doses and
durations of oral steroids were over 5 mg/day for more than 3 months and 1 mg/kg
body weight/day for 6 to 10 days for 4 or more courses/year. The prevalence of
low bone mass was 39% and 61%, respectively. It was not possible to quantify the
overall risk of osteoporosis induced by oral steroids from the studies. No
studies evaluated prevalence of fracture. CONCLUSIONS: Registry studies and
randomized controlled trials would be needed to assess the risk of osteoporosis
in CRSwNP patients and future guidelines should include recommendations regarding
preventive treatment and recommendations on doses and durations of oral steroids.
PMID- 28492610
TI - Nasal cytology in children: scraping or swabbing?
AB - Nasal cytology has become a valuable tool in the assessment of a multitude of
nasal pathologies in children. Collection methods differ significantly and even
though the use of the nasal curette is regarded as the most reliable in adults,
most practitioners use the nasal swab in children. However, no studies have
validated the reliability and supposed better tolerability of the latter. We have
compared these two sampling methods regarding their tolerability and analysed the
diagnostic accuracy of the cotton nasal swab (NSW) to identify nasal cytotypes
and rhinitis phenotypes, using nasal scraping (NSC) for comparison. In a
multicentric prospective study we recruited 208 children and performed nasal
cytology by means of NSW and NSC. Microscopic evaluating of the nasal cytotypes
was performed and tolerability of NSW and NSC was tested. Our data revealed a
significantly inferior diagnostic accuracy of NSW compared to NSC regarding
reliability and cell counts. Our study is the first to shed light on the role of
the sampling tools for pediatric nasal cytology. We documented a poor diagnostic
accuracy of NSW, thus suggesting using only the nasal curette in clinical
practice. Furthermore, tolerability did not differ between the two, refuting the
common thesis that swabs are to be preferred when doing nasal cytology in
children.
PMID- 28492611
TI - The effect of topical treatments for CRS on the sinonasal epithelial barrier.
AB - BACKGROUND: Several topical treatments are used in the management of Chronic
Rhinosinusitis (CRS), some of which the safety and efficacy has yet to be
determined. The purpose of this study was to investigate the effect of commonly
used topical treatments on the sinonasal epithelial barrier. METHODS: Normal
saline (0.9% Sodium Chloride), hypertonic saline (3% Sodium Chloride), FESS Sinu
Cleanse Hypertonic, FLO Sinus Care and Budesonide 1 mg/ 2 ml were applied to the
apical side of air-liquid interface (ALI) cultures of primary human nasal
epithelial cells (HNECs) from CRS patients (n=3) and non-CRS controls (n=3) for
24 hours. Epithelial barrier structure and function was assessed using trans
epithelial electrical resistance (TEER), measuring the passage of Fluorescein
Isothiocyanate labelled Dextrans (FITC-Dextrans) and assessing the expression of
the tight junction protein Zona Occludens-1 (ZO-1) using immunofluorescence.
Toxicity was assessed using a Lactate Dehydrogenase (LDH) assay. Data was
analysed using ANOVA, followed by Tukey HSD post hoc test. RESULTS: Hypertonic
solution and budesonide significantly increased TEER values in CRS derived HNECs.
In contrast, FESS Sinu-Cleanse Hypertonic significantly reduced TEER 5 minutes
after application of the solution followed by an increase in paracellular
permeability of FITC-Dextrans (30 minutes) and increased LDH levels 6 hours after
application of the solution. CONCLUSIONS: Our findings confirm that isotonic and
hypertonic saline solutions do not compromise epithelial barrier function in
vitro but underscore the importance of examining safety and efficacy of over-the
counter wash solutions.
PMID- 28492612
TI - A prospective, randomized clinical study comparing drug eluting stent therapy and
intranasal corticoid steroid therapy in the treatment of patients with chronic
rhinosinusitis.
AB - OBJECTIVES: To conduct the first prospective, randomized controlled clinical
trial comparing the efficacy of a drug-eluting stent (DES) (the Relieva StratusTM
MicroFlow Spacer) and topical intranasal corticosteroid therapy in patients with
chronic rhinosinusitis (CRS). METHODS: Sixty-three adult patients with
ethmoiditis were randomized into either the DES group (n=34) or nasal spray group
(n=29). The main outcome variable was the Sinonasal Outcome Test 22, Visual
Analogue Scale, nasal endoscopy, rhinometric measurements were performed at the
beginning of the study, after three months and six months of follow-up. RESULTS:
Both treatments significantly improved quality of the life with no significant
difference being found between the two groups. The VAS score decreased in both
groups: improvements were significant at three and six months in the nasal spray
group, but in the DES group a significant difference was noted only at three
months. There was a statistically significant increase in total nasal cavity
volumes in the corticosteroid spray group, but not in the DES group. CONCLUSION:
We found that patients benefitted from DES and the corticosteroid nasal spray. We
could not find any significant difference between the treatments, except the
greater increase in the total nasal cavity volumes favouring the nasal spray
group. Because of the very good results for the nasal spray and the much higher
material and operating room costs associated with DES, we cannot recommend the
use of DES over nasal spray as a monotherapeutic treatment for CRS.
PMID- 28492613
TI - Erratum. Correction to: Hu X, et al. Acoustic Radiation Force Impulse (ARFI)
Elastography for non-invasive evaluation of hepatic fibrosis in chronic hepatitis
B and C patients: a systematic review and meta-analysis. Med Ultrason 2017;
19(1):23-3.
AB - The authors have been made aware of the errors that appeared at Corresponding
author: correct phone number 86-10-63138297 and correct email
qianlinxue2002@163.com, and also at acknowledgements: correct grant no. 2014-3
009.
PMID- 28492618
TI - Unexpected coordination number and phase diagram of niobium diselenide under
compression.
AB - We discovered several new energetically competitive structures of NbSe2 using the
multi-algorithm collaborative (MAC) crystal structure prediction algorithm
combined with the density functional theory. It was found that the coordination
number of Nb in NbSe2 is increased from 6 to 7, and then to 8 with increasing
pressure. Furthermore, it was unexpected that an Se atom would be squeezed to the
center of a cage formed by 12 other Se atoms and then have 12-fold coordination
when the pressure was increased to 130.4 GPa. The 12-coordination metalloid atom
has never been discovered in other transition metal dichalcogenides. The new
C2/m, I4/mmm, and P4/mmm NbSe2 were verified to be stable under both dynamically
and mechanically stabile conditions. It is especially noteworthy that the new
C2/m-NbSe2 was predicted to be potentially synthesized at high pressure and
recovered under ambient conditions. A detailed high-pressure and high-temperature
phase diagram was constructed based on the quasi-harmonic approximation up to 200
GPa, and the synthesis conditions of different new NbSe2 materials were also
analyzed. All the discoveries in this study will guide the future synthesis of
new NbSe2 materials at specific pressure and under temperature conditions and
also help to further understand other transition metal dichalcogenides.
PMID- 28492619
TI - The hot carrier diffusion coefficient of sub-10 nm virgin MoS2: uncovered by non
contact optical probing.
AB - We report a novel approach for non-contact simultaneous determination of the hot
carrier diffusion coefficient (D) and interface thermal resistance (R) of sub-10
nm virgin mechanically exfoliated MoS2 nanosheets on c-Si. The effect of hot
carrier diffusion in heat conduction by photon excitation, diffusion, and
recombination is identified by varying the heating spot size from 0.294 MUm to
1.14 MUm (radius) and probing the local temperature rise using Raman
spectroscopy. R is determined as 4.46-7.66 * 10-8 K m2 W-1, indicating excellent
contact between MoS2 and c-Si. D is determined to be 1.18, 1.07, 1.20 and 1.62
cm2 s-1 for 3.6 nm, 5.4 nm, 8.4 nm, and 9.0 nm thick MoS2 samples, showing little
dependence on the thickness. The hot carrier diffusion length (LD) can be
determined without knowledge of the hot carrier's life-time. The four samples LD
is determined as 0.344 (3.6 nm), 0.327 (5.4 nm), 0.346 (8.4 nm), and 0.402 MUm
(9.0 nm). Unlike previous methods that are implemented by making electrical
contact and applying an electric field for D measurement, our technique has the
advantage of being truly non-contact and non-invasive, and is able to
characterize the electron diffusion behavior of virgin 2D materials. Also it
points out that hot carrier diffusion needs to be taken into serious
consideration in Raman-based thermal property characterization of 2D materials,
especially under very tightly focused laser heating whose spot size is comparable
to the hot carrier diffusion length.
PMID- 28492620
TI - Novel red phosphors KBaEu(XO4)3 (X = Mo, W) show high color purity and high
thermostability from a disordered chained structure.
AB - Two novel red phosphors KBaEu(XO4)3 (X = Mo, W) have been synthesized by high
temperature solid-state reactions and the crystal structures were determined for
the first time. Single-crystal X-ray diffraction data reveal that their space
groups are C2/c. The crystalline structure is constituted of K/BaO8 distorted
square antiprisms and distorted EuO8 polyhedra which form chains lying along the
c-axis and two kinds of distorted XO4 tetrahedra. This high disorder of K/Ba
which might lower the crystal field symmetry around Eu3+ results in the high
purity of red emission around 615 nm originating from 5D0 -> 7F2 transition under
near-ultraviolet (NUV) excitation. With increasing temperature, the luminescence
of KBaEu(XO4)3 (X = Mo, W) phosphors decreases almost linearly with subtle
alteration for the CIE coordinate. As the temperature reaches 550 K, the red
emission intensity decreases to 37.3% and 50.7% of that at 300 K for KBaEu(MoO4)3
and KBaEu(WO4)3, respectively. The analysis of the decay curves of the 5D0 -> 7F2
emission at variable temperatures indicates the weak cross relaxation and non
radiative energy transfer between Eu3+ ions. These results demonstrate that the
investigated phosphors are attractive for application in high power NUV excited
white LEDs.
PMID- 28492621
TI - Leaf parts from Greek artichoke genotypes as a good source of bioactive compounds
and antioxidants.
AB - Globe artichoke is an important vegetable in the Mediterranean diet. However, the
marketable part of the plant constitutes a small portion of its total crop
biomass and large amounts of waste are produced during its cultivation. In this
study, the phenolic compound content and composition and the antioxidant activity
of leaf parts [blades (SLB), petioles and midribs (SPM)] from various Greek
artichoke genotypes were evaluated. The results showed significant variation in
antioxidant activities and bioactive compound contents between the studied
genotypes, with the leaf blades of most of the genotypes having a high content of
flavonoids (mainly luteolin glycoside derivatives), which ranged between 49 and
78% of total phenolic compounds (TPC). In contrast, in petioles and midribs
phenolic acids (mainly hydroxycinnamic acid derivatives) were the main phenolic
compounds, ranging between 64 and 76% of TPC. The antioxidant activity of blades
was significantly higher than that of petiole and midribs for all the genotypes
and the tested assays. In conclusion, artichoke leaves (blades, petioles and
midribs) of the studied genotypes showed different bioactive compound profiles
and significant antioxidant properties, and could be further used in the food and
nutraceuticals industries as a cheap source of phenolic compounds and
antioxidants.
PMID- 28492622
TI - Isolated, well-defined organovanadium(iii) on silica: single-site catalyst for
hydrogenation of alkenes and alkynes.
AB - A well-defined, isolated, single-site organovanadium(iii) catalyst on SiO2
[(SiO2)V(Mes)(THF)] was synthesized via surface organometallic chemistry, and
fully characterized using a combination of analytical and spectroscopic
techniques (EA, ICP, 1H NMR, TGA-MS, EPR, XPS, DR-UV/Vis, UV-Raman, DRIFTS, XAS).
The catalyst exhibits unprecedented reactivity in liquid- and gas-phase
alkene/alkyne hydrogenation. Kinetic poisoning experiments revealed that 100% of
the V sites are active for hydrogenation.
PMID- 28492623
TI - The use of carboxylic acids as traceless directing groups for regioselective C-H
bond functionalisation.
AB - The ability to selectively functionalise a specific C-H bond is a long-standing
challenge due to the ubiquity of such bonds in organic molecules. One of the most
common approaches to overcome this obstacle consists of installing directing
groups into substrates to direct the functionalisation towards the desired C-H
bond, leaving behind the directing group in the molecule. Alternatively,
carboxylic acids have been employed as traceless directing groups that are easily
removed after carboxylic acid-directed installation of the desired functionality.
This review focuses on the development of this concept and its application to
organic synthesis during the last decade.
PMID- 28492624
TI - A simple quinolone Schiff-base containing CHEF based fluorescence 'turn-on'
chemosensor for distinguishing Zn2+ and Hg2+ with high sensitivity, selectivity
and reversibility.
AB - A new simple 'dual' chemosensor MQA ((E)-2-methoxy-N-((quinolin-2
yl)methylene)aniline) for distinguishing Zn2+ and Hg2+ has been designed,
synthesized and characterized. The sensor showed excellent selectivity and
sensitivity with a fluorescence enhancement to Zn2+/Hg2+ over other commonly
coexisting cations (such as Na+, Mg2+, Al3+, K+, Mn2+, Fe2+, Fe3+, Co2+, Ni2+,
Cu2+, Ga3+, Cd2+, In3+ and Pb2+) in DMSO-H2O solution (1/99 v/v), which was
reversible with the addition of ethylenediaminetetraacetic acid (EDTA). The
detection limit for Zn2+/Hg2+ by MQA both reached the 10-8 M level. The 1 : 1
ligand-to-metal coordination patterns of the MQA-Zn2+ and MQA-Hg2+ were
calculated through a Job's plot and ESI-MS spectra, and were further confirmed by
X-ray crystal structures of complexes MQA-Zn2+ and MQA-Hg2+. This chemosensor can
recognize similar metal ions by coherently utilizing intramolecular charge
transfer (ICT) and different electronic affinities of various metal ions. DFT
calculations have revealed that the energy gap between the HOMO and LUMO of MQA
has decreased upon coordination with Zn(ii)/Hg(ii).
PMID- 28492625
TI - Thermal convection in electrochemical cells. Boundaries with heterogeneous
thermal conductivity and implications for scanning electrochemical microscopy.
AB - We investigate the heat transfer in a cylinder-shaped electrochemical cell with
solid, thermally insulating walls. The cell is filled with a liquid and a solid
substrate that is thermostated from below is situated at its base. The initial
temperature of the liquid is different from that of the substrate so as to mimic
imperfect thermostating in an electrochemical experiment; as heat transfer acts
to diminish the temperature difference between the two, natural convection
ensues. The influence of inhomogeneities in the thermal conductivity of the solid
is studied - numerical simulations of the heat transfer in the system are
conducted for substrates that are comprised of a thermally conductive material,
an insulating one or a combination thereof. It is shown that the substrate
structure strongly influences the structure and intensity of the natural
convective flows emerging in the system. The present work demonstrates that under
the idealized conditions under consideration, depending on the substrate
structure, natural convection due to imperfect solution thermostating may give
rise to flows whose local velocity can reach values as high as 10-3 m s-1.
Moreover, as comparison between cells of two different radii shows, both the
intensity and the temporal evolution of the flows arising in this system are
highly sensitive to the precise geometry of the experimental cell. These results
can have far-reaching consequences for the interpretation of results from
experimental techniques such as scanning electrochemical microscopy.
PMID- 28492626
TI - Alkynyl sulfoxides as alpha-sulfinyl carbene equivalents: gold-catalysed
oxidative cyclopropanation.
AB - Alkynyl sulfoxides are shown to act as alpha-sulfinyl metallocarbene synthons
under oxidative gold catalysis, enabling reactions that are not available from
diazo-precursors. This strategy is exemplified in the synthesis of fused alpha
sulfinyl cyclopropanes.
PMID- 28492627
TI - Analysis of the electron transfer properties of carbon quantum dots on gold
nanorod surfaces via plasmonic resonance scattering spectroscopy.
AB - Carbon quantum dot wrapped gold nanorods were fabricated on an ITO electrode
surface via electrostatic interactions. The electron transfer properties of
carbon quantum dots on gold nanorod surfaces were systematically investigated by
plasmonic resonance scattering spectroscopy.
PMID- 28492628
TI - Lanthanide separation using size-selective crystallization of Ln-MOFs.
AB - Herein, we report an elaborate method, size-selective crystallization of Ln-MOFs,
to isolate lanthanide (Ln) ions. Herein, 13 lanthanide ions, except for the
radioactive Pm(iii) ion, were separated by four types of Ln-MOFs: type I (La-Pr),
type II (Nd-Eu), type III (Gd-Ho), and type IV (Er-Lu). Further systemic
investigation also suggested the highly selective separation of lanthanide ions
by this method.
PMID- 28492629
TI - Liquid/vapor-induced reversible dynamic structural transformation of a three
dimensional Cu-based MOF to a one-dimensional MOF showing gate adsorption.
AB - A new 3D metal-organic framework (MOF), in which 2D layers are interlaced to form
a 3D architecture, was synthesized by a reaction of Cu(BF4)2 and 1,3-bis(4
pyridyl)propane (bpp) in a water/1-hexanol solvent system, and the crystal
structure of the MOF was successfully solved. The MOF is reversibly transformed
to a 1D chain MOF, which shows gate adsorption properties. The dynamic
transformation gives crystal size reduction resulting in a slight change in CO2
adsorption isotherms. The 1D MOF shows selective adsorption/separation properties
on benzene and its analogues with similar sizes and shapes (benzene, toluene, and
cyclohexane).
PMID- 28492630
TI - One-step large-scale highly active g-C3N4 nanosheets for efficient sunlight
driven photocatalytic hydrogen production.
AB - The development of highly active, cost-effective, environmentally friendly and
stable g-C3N4 based photocatalysts for H2 evolution is one of the most
anticipated potential pathways for future hydrogen utilization. Herein, a facile
gaseous bubble template approach was designed to prepare large-scale thin g-C3N4
nanosheets (g-C3N4 NSs) using melamine and ammonium sulphate as the bubble
template. Through distinctive structural improvements for a large bandgap,
excellent electron mobility, prolonged lifetime of the photogenerated charge
carriers and a high specific surface area with highly accessible potential
reaction sites, the as-synthesized g-C3N4 NSs demonstrated a high photocatalytic
hydrogen evolution rate of 9871 MUmol h-1 g-1 and efficient photocatalytic
degradation of Rhodamine B (RhB) and phenol under simulated solar light
irradiation.
PMID- 28492631
TI - Molecular tectonics: gas adsorption and chiral uptake of (l)- and (d)-tryptophan
by homochiral porous coordination polymers.
AB - Combinations of two enantiomerically pure organic tectons 1 and 3 with either
Zn(ii) or Cu(ii) cations lead to the formation of four homochiral 3D networks
among which two, 1-Cu and 3-Cu, are robust porous crystals displaying homochiral
cavities and permanent microporosity. 3-Cu porous crystals capture 66% and 20% of
l- and d-tryptophan, respectively, after 30 min of adsorption.
PMID- 28492632
TI - Photo-assisted inactivation of Escherichia coli bacteria by silver functionalized
titanate nanotubes, Ag/H2Ti2O5.H2O.
AB - One-dimensional titanate nanotubes (H2Ti2O5.H2O) functionalized with silver
nanoparticles (AgNPs) exhibited unique properties for the effective inactivation
of the Gram-negative Escherichia coli within 45 minutes under irradiation using a
65 W halogen lamp. The pathway of the photo-assisted catalytic inactivation was
examined by SEM and TEM using a reproducible biological protocol for sample
preparations. The membrane integrity of the bacteria was damaged due to the
oxidative stress caused by the reactive oxygen species, the bacteriostatic effect
of the highly-dispersed-surface AgNPs (~5 nm) and the sharp nanotube penetration
that induced the cell death.
PMID- 28492633
TI - Rational molecular design enhancing the photonic performance of red-emitting
perylene bisimide dyes.
AB - We report the synthesis of novel multichromophoric organic architectures, where
perylene red is decorated with BODIPY and/or hydroxycoumarin dyes acting as light
harvesters and energy donors. The computationally-aided photophysical study of
these molecular assemblies reveals a broadband absorption which, regardless of
the excitation wavelength, leads solely to a bright red-edge emission from
perylene bisimide after efficient intramolecular energy transfer hops. The
increase of the absorbance of these molecular antennas at key pumping wavelengths
enhances the laser action of the commercial perylene red. The herein applied
strategy based on energy transfer dye lasers should boost the use of perylene
based dyes as active media for red-emitting lasers.
PMID- 28492634
TI - Transcriptional regulatory proteins as biosensing tools.
AB - We have developed sensing systems employing different classes of transcriptional
regulatory proteins genetically and chemically modified to incorporate a
fluorescent reporter molecule for detection of arsenic, hydroxylated
polychlorinated biphenyls (OH-PCBs), and cyclic AMP (cAMP). These are the first
examples of optical sensing systems based on transcriptional regulatory proteins.
PMID- 28492640
TI - Impedimetric measurement of DNA-DNA hybridisation using microelectrodes with
different radii for detection of methicillin resistant Staphylococcus aureus
(MRSA).
AB - Due to their electroanalytical advantages, microelectrodes are a very attractive
technology for sensing and monitoring applications. One highly important
application is measurement of DNA hybridisation to detect a wide range of
clinically important phenomena, including single nucleotide polymorphisms (SNPs),
mutations and drug resistance genes. The use of electrochemical impedance
spectroscopy (EIS) for measurement of DNA hybridisation is well established for
large electrodes but as yet remains relatively unexplored for microelectrodes due
to difficulties associated with electrode functionalisation and impedimetric
response interpretation. To shed light on this, microelectrodes were initially
fabricated using photolithography and characterised electrochemically to ensure
their responses matched established theory. Electrodes with different radii (50,
25, 15 and 5 MUm) were then functionalised with a mixed film of 6-mercapto-1
hexanol and a thiolated single stranded DNA capture probe for a specific gene
from the antibiotic resistant bacterium MRSA. The complementary oligonucleotide
target from the mecA MRSA gene was hybridised with the surface tethered ssDNA
probe. The EIS response was evaluated as a function of electrode radius and it
was found that charge-transfer (RCT) was more significantly affected by
hybridisation of the mecA gene than the non-linear resistance (RNL) which is
associated with the steady state current. The discrimination of mecA
hybridisation improved as electrode radius reduced with the RCT component of the
response becoming increasingly dominant for smaller radii. It was possible to
utilise these findings to produce a real time measurement of oligonucleotide
binding where changes in RCT were evident one minute after nanomolar target
addition. These data provide a systematic account of the effect of microelectrode
radius on the measurement of hybridisation, providing insight into critical
aspects of sensor design and implementation for the measurement of clinically
important DNA sequences. The findings open up the possibility of developing
rapid, sensitive DNA based measurements using microelectrodes.
PMID- 28492641
TI - Rapid synthesis of bicyclic lactones via palladium-catalyzed aminocarbonylative
lactonizations.
AB - A novel and efficient palladium-catalyzed aminocarbonylative lactonization of
amino propargylic alcohols has been developed to provide rapid access to various
bicyclic lactones especially dihydropyrrole-fused furanones, which are novel
structures and have not been explored in biological and medicinal settings. This
method can also be used to access beta-lactone products such as 16. Preliminary
biological evaluations revealed that compounds 13h and 13s demonstrated promising
activity against Clostridium difficile and compounds 13h, 13k, 13s, and 16b
showed activity against several important fungal pathogens.
PMID- 28492642
TI - Copper-catalyzed remote (delta) C(sp3)-H bond amination: a practical strategy to
construct pyrrolidine derivatives.
AB - We report a copper-catalyzed remote C(sp3)-H bond amination reaction that
converts acyclic amines to pyrrolidines. This reaction occurs selectively at the
carbon delta to the amine functionality. Primary, secondary and tertiary C-H
bonds are all suitable for the amination reactions in the presence of an
inexpensive and commercially available copper catalyst.
PMID- 28492643
TI - The influence of substituents and the environment on the NMR shielding constants
of supramolecular complexes based on A-T and A-U base pairs.
AB - In the present study, we have theoretically analyzed supramolecular complexes
based on the Watson-Crick A-T and A-U base pairs using dispersion-corrected
density functional theory (DFT). Hydrogen atoms H8 and/or H6 in the natural
adenine and thymine/uracil bases were replaced, respectively, by substituents X8,
Y6 = NH-, NH2, NH3+ (N series), O-, OH, OH2+ (O series), F, Cl or Br (halogen
series). We examined the effect of the substituents on the hydrogen-bond lengths,
strength and bonding mechanism, and the NMR shielding constants of the C2-adenine
and C2-thymine/uracil atoms in the base pairs. The general belief in the
literature that there is a direct connection between changes in the hydrogen-bond
strength and the C2-adenine shielding constant is conclusively rejected by our
computations.
PMID- 28492644
TI - Temperature switchable Bronsted acid-promoted selective syntheses of spiro
indolenines and quinolines.
AB - A high-yielding, temperature switchable divergent approach towards the synthesis
of either spiro-indolenines or quinolines is described, starting from easily
available indolyl ynones. The application of TFA at rt promotes the
dearomatization of the indole, resulting in the formation of the spiro
indolenine, while at higher temperature, rearrangement results in the formation
of the quinoline.
PMID- 28492645
TI - A coordination strategy to realize a sextuply-bonded complex.
AB - The synthesis of higher-order multiple bonds is a great challenge in chemistry.
However, no stable compound with a sextuple bond has been reported, except for
Mo2 in an inert matrix at low temperatures. Herein, we propose a strategy to
construct a sextuple bond in a dinuclear transition metal complex based on
complete active space second-order perturbation theory (CASPT2) and density
functional theory calculations. When the dinuclear core M2 (M = W, Mo, and Re+)
is capped by two neutral electron-donating ligands at both M-M ends, a sextuple
bond can be realized. The proposed ligands stabilize the M2 core by the
coordination, conserve the six bonding orbitals in the occupied space, and
suppress the weight of the delta-delta* excited electronic configuration.
Calculated large formation energies of these complexes indicate the large
possibility of the synthesis. Electronic structures and sextuply bonding
interactions were analyzed in detail.
PMID- 28492646
TI - High pressure micromechanical force measurements of the effects of surface
corrosion and salinity on CH4/C2H6 hydrate particle-surface interactions.
AB - In order to investigate the mechanism of gas hydrate deposition and agglomeration
in gas dominated flowlines, a high-pressure micromechanical force (MMF) apparatus
was applied to directly measure CH4/C2H6 hydrate adhesion/cohesion forces under
low temperature and high pressure conditions. A CH4/C2H6 gas mixture was used as
the hydrate former. Adhesion forces between hydrate particles and carbon steel
(CS) surfaces were measured, and the effects of corrosion on adhesion forces were
analyzed. The influences of NaCl concentration on the cohesion force between
CH4/C2H6 hydrate particles were also studied for gas-dominated systems. It was
observed that there was no measurable adhesion force for pristine (no corrosion)
and corroded surfaces, when there was no condensed water or water droplet on
these surfaces. With water on the surface (the estimated water amount was around
1.7 MUg mm-2), a hydrate film growth process was observed during the measurement.
CS samples were soaked in NaCl solution to obtain different extents of corrosion
on surfaces, and adhesion measurements were performed on both pristine and
corroded samples. The adhesion force was found to increase with increasing soak
times in 5 wt% NaCl (resulting in more visual corrosion) by up to 500%. For the
effect of salinity on cohesion forces, it was found that the presence of NaCl
decreased the cohesion force between hydrate particles, and a possible
explanation of this phenomenon was given based on the capillary liquid bridge
model.
PMID- 28492647
TI - Synthesis of water-soluble palladium(ii) complexes with N-heterocyclic carbene
chelate ligands and their use in the aerobic oxidation of 1-phenylethanol.
AB - The synthesis of palladium(ii) complexes containing N-heterocyclic carbene
chelate ligands is reported. These chelate ligands have methylene or ethylene
ring bridges and sulfonate, carbonate or ammonium functionalities to render the
complexes soluble in water. Bis- [(bis-NHC)PdX2] (X = Cl, Br or I) and tetra
carbene [(bis-NHC)2Pd] complexes have been prepared and the crystal structures of
two of them have been determined. The NHC ligand is coordinated to the metal
center in normal (C2-bound) or abnormal (C4-bound) mode. Processes involving the
formation of NHC-Pd bonds or the transfer of NHC ligands have been explored in
water. The behavior of the bis-carbene complexes as catalysts for the aerobic
oxidation of 1-phenylethanol is also discussed.
PMID- 28492648
TI - Unifying hydrotropy under Gibbs phase rule.
AB - The task of elucidating the mechanism of solubility enhancement using hydrotropes
has been hampered by the wide variety of phase behaviour that hydrotropes can
exhibit, encompassing near-ideal aqueous solution, self-association, micelle
formation, and micro-emulsions. Instead of taking a field guide or encyclopedic
approach to classify hydrotropes into different molecular classes, we take a
rational approach aiming at constructing a unified theory of hydrotropy based
upon the first principles of statistical thermodynamics. Achieving this aim can
be facilitated by the two key concepts: (1) the Gibbs phase rule as the basis of
classifying the hydrotropes in terms of the degrees of freedom and the number of
variables to modulate the solvation free energy; (2) the Kirkwood-Buff integrals
to quantify the interactions between the species and their relative contributions
to the process of solubilization. We demonstrate that the application of the two
key concepts can in principle be used to distinguish the different molecular
scenarios at work under apparently similar solubility curves observed from
experiments. In addition, a generalization of our previous approach to solutes
beyond dilution reveals the unified mechanism of hydrotropy, driven by a strong
solute-hydrotrope interaction which overcomes the apparent per-hydrotrope
inefficiency due to hydrotrope self-clustering.
PMID- 28492649
TI - Identifying electrochemical effects in a thermal-electrochemical co-driven system
for CO2 capture.
AB - Currently, the most promising amine absorption system for CO2 capture still faces
the challenges of heavy steam consumption and a high energy penalty. Thus, a new
thermal-electrochemical co-driven system (TECS) for CO2 capture was developed to
resolve these problems. In the TECS, unknown electrochemical behaviors are quite
essential to assess the CO2 capture performance. Electrochemical experiments were
designed using response surface methodology (RSM) to identify electrochemical
effects. The results show that the cathode process is slow and difficult, which
is the main limitation in improving the performance of the TECS. Forced
convection is necessary to improve the diffusion-controlled process and
accelerate desorption. Four factors (Cu(ii) molality, CO2 loading, temperature,
KNO3 molality) play an auxo-action role in determining anode and cathode reaction
rates. A regression model is developed based on the experimental data, and
optimum operating conditions are obtained. Regeneration energy consumption
reaches about 1.3 GJ per t CO2, a decline of up to 70% compared with the
traditional process. In addition, preliminary CO2 desorption experiments suggest
that the mass transfer ascribed to the electrochemical process accounts for over
50% of the overall mass transfer coefficient in the CO2 desorption process.
PMID- 28492650
TI - Stabilization of a t-ZrO2 polymorph in a glassy SiO2 matrix at elevated
temperatures accomplished by ceria additions.
AB - Glass-ceramic composites are considered important candidates for load bearing
orthopaedic applications owing to their combined salient features of bioactivity
and mechanical strength. Herein, we report the impact of ceria (CeO2) additions
on the structural and mechanical behaviour of ZrO2-SiO2 binary oxides as a glass
ceramic composite for hard tissue replacements. A wide range of ceria additions
to the ZrO2-SiO2 system have been performed via sol-gel synthesis. The structural
behaviour of the synthesized compositions is investigated at elevated
temperatures using a combination of XRD, Raman spectroscopy, TEM and SEM. The
stabilization of tetragonal zirconia (t-ZrO2) and CeO2 in the presence of an
amorphous SiO2 matrix under heat treatment up to 1300 degrees C was confirmed.
The t-ZrO2 phase is stabilised through Ce4+ substitution up to 20 wt% CeO2
additions, and above this CeO2 crystallization occurs in the amorphous matrix.
The morphological and mechanical behaviour of the ceramic reinforced glass matrix
is presented with the CeO2 stabilised system showing mechanical properties
comparable with commercial biomaterial systems.
PMID- 28492651
TI - The influence of carbon concentration on the electronic structure and magnetic
properties of carbon implanted ZnO thin films.
AB - The influence of carbon concentration on the electronic and magnetic properties
of C-implanted ZnO thin films has been studied using synchrotron radiation based
X-ray absorption spectroscopic techniques and vibrating sample magnetometer
measurements. 20 keV carbon ions were implanted in ZnO films with different
fluences (2 * 1016, 4 * 1016 and 6 * 1016 ions per cm2). The pristine ZnO film
shows diamagnetic behaviour while the C-implanted films exhibit room temperature
ferromagnetism. Our first-principles calculations based on density functional
theory show an appreciable magnetic moment only when the implanted C atom sits
either in the O-site (2 MUB) or in the interstitial position (1.88 MUB), whereas
the C atom in the Zn substitutional position does not possess any magnetic
moment. X-ray absorption near edge structure analysis at the O K-edge reveals
that the charge transfer from O-2p to the C-defect site causes the ferromagnetism
in the C-implanted ZnO film at low fluence. However at high fluence, the
implanted C replaces the lattice and produces more Zn vacancies, as evidenced by
extended X-ray absorption fine structure studies at the Zn K-edge, which favors
the ferromagnetism. The persistence of the implanted carbon and ferromagnetism of
the C-implanted ZnO film has also been studied by isothermal annealing at 500
degrees C and discussed in detail.
PMID- 28492652
TI - Low energy electron-induced decomposition of (eta3-C3H5)Ru(CO)3Br, a potential
focused electron beam induced deposition precursor with a heteroleptic ligand
set.
AB - Here we describe in detail low energy electron induced fragmentation of a
potential focused electron beam induced deposition (FEBID) precursor, pi-allyl
ruthenium tricarbonyl bromide, i.e. (eta3-C3H5)Ru(CO)3Br, specially designed to
allow comparison of the effect of different ligands on the efficiency of low
energy electron induced fragmentation of FEBID precursors. Specifically, we
discuss the efficiency of dissociative electron attachment (DEA) and dissociative
ionization (DI) with respect to electron-induced removal of the allyl, bromide
and carbonyl ligands. We place this in perspective with a previous surface study
on the same precursor and we propose a design strategy for FEBID precursor
molecules to increase their susceptibility towards DEA.
PMID- 28492654
TI - Microstructure based prediction of the deformation behavior of soft collagenous
membranes.
AB - The response of human amnion (HA) and bovine Glisson's capsule (GC) to uniaxial
and biaxial tensile loading is analyzed on tissue (~mm) and collagen fiber (~MUm)
length scales. The mechanical behavior of the membranes is rationalized based on
a discrete fiber network model that relates model parameters with microstructural
features of the tissues. Parameters were first determined for GC based on the
quantity and organization of collagen fibers in the tissue. Next, parameters for
HA were defined by comparing the microstructures of the two membranes, which
differ in fiber organization in that collagen forms MUm-thick fiber bundles in GC
while 50 nm-thin fibrils constitute the network in HA. The flexural behavior of
these structures is phenomenologically represented in the model, indicating that
shear forces are transmitted through fibrils within GC bundles, but to a much
lesser extent than in a corresponding solid cross section. The model provides
excellent predictions of the uniaxial and biaxial mechanical response, as well as
of the progressive reorientation of fibers associated with uniaxial loading. The
results are particularly relevant since model parameters were not obtained
through a fitting procedure of the tissue's tension-stretch curve. Furthermore,
simulations of representative in vivo deformation states indicated that a large
part of the fibers are expected to be un-crimped under physiological loading
conditions. Thus, the crimped shape of collagen fibers in the initial test
configuration, and typically observed in histological analyses, might be a
consequence of the contraction occurring when membranes are extracted from their
environment in the body.
PMID- 28492653
TI - Self-assembled core-polyethylene glycol-lipid shell nanoparticles demonstrate
high stability in shear flow.
AB - A core-polyethylene glycol-lipid shell (CPLS) nanoparticle consists of an
inorganic core coated with polyethylene glycol (PEG) polymers, surrounded by a
lipid bilayer shell. It can be self-assembled from a PEGylated core with surface
tethered PEG chains, where all the distal ends are covalently bonded to lipid
molecules. Upon adding free lipids, a complete lipid bilayer shell can be formed
on the surface driven by the hydrophobic nature of lipid tails, leading to the
formation of a CPLS nanoparticle. The stability of CPLS nanoparticles in shear
flow has been systematically studied through large scale dissipative particle
dynamics simulations. CPLS nanoparticles demonstrate higher stability and less
deformation in shear flow, compared with lipid vesicles. Burst leakage of drug
molecules inside lipid vesicles and CPLS NPs can be induced by the large pores at
their tips. These pores are initiated by the maximum stress in the waist region.
It further grows along with the tank-treading motion of vesicles or CPLS NPs in
shear flow. However, due to the constraints applied by PEG polymers, CPLS NPs are
less deformed than vesicles with comparable size under the same flow conditions.
Thus, the less deformed CPLS NPs express a smaller maximum stress at waists,
demonstrating higher stability. Pore formation at waists, evolving into large
pores on vesicles, leads to the burst leakage of drug molecules and complete
rupture of vesicles. In contrast, although similar drug leakage in CPLS
nanoparticles can occur at high shear rates, pores initiated at moderate shear
rates tend to be short-lived and close due to the constraints mediated by PEG
polymers. This kind of 'self-healing' capability can be observed over a wide
range of shear rates for CPLS nanoparticles. Our results suggest self-assembled
CPLS nanoparticles to exhibit high stability during blood circulation without
rapid drug leakage. These features make CPLS nanoparticles candidates for a
promising drug delivery platform.
PMID- 28492655
TI - Formation of modulated phases and domain rigidification in fatty acid-containing
lipid membranes.
AB - We investigated the phase behavior of lipid membranes containing fatty acids
(FAs) by microscopy and differential scanning calorimetry. We used palmitic acid
(saturated FA), oleic acid (cis-isomer of unsaturated FA), elaidic acid (trans
isomer of unsaturated FA), and phytanic acid (branched FA) and examined the
effects of FAs on phase-separated structures in lipid bilayer membranes
consisting of dioleolylphosphocholine (DOPC)/dipalmitoylphosphocholine
(DPPC)/cholesterol (Chol). Palmitic acid and elaidic acid exclude Chol from the
DPPC-rich phase. As a result, the liquid-ordered phase formed by DPPC and Chol
transforms into a solid-ordered phase. Oleic acid and phytanic acid significantly
reduce the line tension at the liquid domain boundary. This decrease in line
tension leads to the formation of modulated phases, such as striped, hexagonal,
and polygonal domains. We measured the line tension and the interdomain
interaction in these specific domains by an image analysis. The result showed
that oleic acid and phytanic acid-containing vesicles as well as palmitic acid
containing vesicles are not spherical, and this domain-induced deformation is
explained theoretically.
PMID- 28492656
TI - A study on one-step laser nanopatterning onto copper-hydrazone-complex thin films
and its mechanism.
AB - Semiconductor diode-based laser patterning with visible light has been
extensively applied to the fabrication of arbitrary structures. However,
recently, the technique has faced a great challenge because it cannot meet
nanoscale-resolved patterning fabrication due to the optical diffraction limit,
which is an inherent drawback in the field of optics. To attack the question,
copper(ii)-hydrazone-complex (CuL2) thin films are used as laser patterning
materials. Under the heating of a writing laser spot, one-step laser
nanopatterning on the CuL2 thin films is obtained. The convex-type and concave
type pattern structures are directly written without wet-etching and developing
processes. The minimum pattern feature size is about 31 nm, which is far smaller
than the diffraction limit and only ~1/20 the writing spot size. Analysis
indicates that the laser nanopatterning originates from obvious photothermal
localization responses to the writing spot. Compared with common organic resists,
the exposure dose of CuL2 is several orders higher than that of the polymer; thus
CuL2 thin film materials are suitable for maskless direct laser writing
lithography. This work also provides an effective method for one-step
nanopatternings through diode-based laser writing at visible light wavelengths.
PMID- 28492657
TI - Outstanding Reviewers for Chemical Society Reviews in 2016.
PMID- 28492658
TI - Interconnected macroporous 3D scaffolds templated from gelatin nanoparticle
stabilized high internal phase emulsions for biomedical applications.
AB - Here we report on the successful preparation of open-cellular macroporous 3D
scaffolds templated from gelatin nanoparticle-stabilized HIPEs with acrylamide
(AM) as the monomer in the continuous phase. Tuning the gelatin nanoparticle
concentration or AM content led to different porous structures with void
diameters varying between 30 and 78 MUm. More importantly, keeping HIPEs at room
temperature to undergo a limited kinetic coarsening before polymerization could
greatly improve the interconnectivity and pore size of the scaffolds, with the
average diameters (approx. 118 MUm) being enlarged 1.5-fold. Additionally, the
scaffolds had a character of soft tissue with compressive modulus more than 150
kPa. The cell culture assay confirmed that HepG2 cells not only could adsorb on
but also were grown inside the scaffolds, representing a characteristic of the
good biocompatibility of the scaffolds. Our work suggests that the 3D scaffolds
fabricated from gelatin nanoparticle-stabilized HIPE templates are promising
culture substrates for a wide range of applications in the biomedical field.
PMID- 28492660
TI - Selective vesicle aggregation achieved via the self-assembly of terpyridine-based
building blocks.
AB - Herein, we report the self-assembly of a mono terpyridine-based building block
modified with long alkyl chains, which gives rise to vesicular aggregates in
aqueous media. The vesicles are responsive to transition metal ions, and form
different kinds of aggregates after metal-ligand coordination. In particular,
Ni(ii) shows a unique influence on morphological transitions, whereby vesicles
aggregate and fuse upon the addition of Ni(ii) ions. Spectroscopic and
morphological studies are highlighted in this work. Furthermore, the formed
vesicles could behave as a matrix for encapsulating fluorescent dyes with similar
molecular structure via co-assembly, enabling more accurate observation of
vesicle aggregation via confocal laser scanning techniques.
PMID- 28492659
TI - Ensemble clustering of phosphoproteomic data identifies differences in protein
interactions and cell-cell junction integrity of HER2-overexpressing cells.
AB - Overexpression of HER2, a receptor tyrosine kinase of the ERBB family, in breast
cancer is related to increased cancer progression and aggressiveness. A breast
epithelial cell model with the single perturbation of HER2 overexpression is
capable of replicating the increased aggressiveness of HER2 overexpressing
cancers. In previous work, Wolf-Yadlin and colleagues (Wolf-Yadlin et al., Mol.
Syst. Biol., 2006, 2) measured the proximal tyrosine phosphorylation dynamics of
the parental and HER2 overexpressing cells (24H) in response to EGF. Here, we
apply an ensemble clustering approach to dynamic phosphorylation measurements of
the two cell models in order to identify signaling events that explain the
increased migratory potential of HER2 overexpressing cells. The use of an
ensemble approach for identifying relationships within a dataset and how these
relationships change across datasets uncovers relationships that cannot be found
by the direct comparison of dynamic responses in the two conditions. Of
particular note is a drastic change in the clustering of SHC1 phosphorylation (on
site Y349) from an EGFR-MAPK module in parental cells to a module consisting of
an E-cadherin junction protein phosphorylation site, catenin delta-1 Y228, in
HER2 overexpressing (24H) cells. Given the importance of E-cadherin junctions in
healthy epithelial wound healing and migration, we chose to test the
computationally-derived identification of altered cell junctions and CTNND1:SHC1
relationships. Our cell and molecular biology experiments demonstrate that SHC
and CTNND1 interact in an EGF- and HER2-dependent manner and that the cell
junctions are phenotypically affected by HER2, breaking down in response to EGF
and yet avoiding apoptosis as a result of cell junction loss. The results suggest
a mechanism by which HER2 alters the localization of the SHC-MAPK signaling axis
and a phenotypic effect on cell junction integrity.
PMID- 28492661
TI - Improved catalysts for hydrogen evolution reaction in alkaline solutions through
the electrochemical formation of nickel-reduced graphene oxide interface.
AB - H2 production via water electrolysis plays an important role in hydrogen economy.
Hence, novel cheap electrocatalysts for the hydrogen evolution reaction (HER) are
constantly needed. Here, we describe a simple method for the preparation of
composite catalysts for H2 evolution, consisting in simultaneous reduction of the
graphene oxide film, and electrochemical deposition of Ni on its surface. The
obtained composites (Ni@rGO), compared to pure electrodeposited Ni, show an
improved electrocatalytic activity towards HER in alkaline media. We found that
the activity of the Ni@rGO catalysts depends on the surface composition (Ni vs. C
mole ratio) and on the level of structural disorder of the rGO support. We
suggest that HER activity is improved via Hads spillover from the Ni particles to
the rGO support, where quick recombination to molecular hydrogen is favored. A
deeper insight into such a mechanism of H2 production was achieved by kinetic
Monte-Carlo simulations. These simulations enabled the reproduction of
experimentally observed trends under the assumption that the support can act as a
Hads acceptor. We expect that the proposed procedure for the production of novel
HER catalysts could be generalized and lead to the development of a new
generation of HER catalysts by tailoring the catalyst/support interface.
PMID- 28492662
TI - Giant magnetic anisotropy of rare-earth adatoms and dimers adsorbed by graphene
oxide.
AB - Nowadays, transition-metal adatoms and dimers with giant magnetic anisotropy have
attracted much attention due to their potential applications in data storage,
spintronics and quantum computations. Using density-functional calculations, we
investigated the magnetic anisotropy of the rare-earth adatoms and dimers
adsorbed by graphene oxide. Our calculations reveal that the adatoms of Tm, Er
and Sm possess giant magnetic anisotropy, typically larger than 40 meV. When the
dimers of (Tm,Er,Sm)-Ir are adsorbed onto graphene oxide, the magnetic anisotropy
even exceeds 200 meV. The magnetic anisotropy can be tuned by the external
electric field as well as the environment.
PMID- 28492663
TI - A versatile microfluidic device for high throughput production of microparticles
and cell microencapsulation.
AB - Biocompatible microparticles are valuable tools in biomedical research for
applications such as drug delivery, cell transplantation therapy, and analytical
assays. However, their translation into clinical research and the pharmaceutical
industry has been slow due to the lack of techniques that can produce
microparticles with controlled physicochemical properties at high throughput. We
introduce a robust microfluidic platform for the production of relatively
homogeneous microdroplets at a generation frequency of up to 3.1 MHz, which is
about three orders of magnitude higher than the production rate of a conventional
microfluidic drop maker. We demonstrated the successful implementation of our
device for production of biocompatible microparticles with various crosslinking
mechanisms and cell microencapsulation with high cell viability.
PMID- 28492664
TI - Size-tunable, highly sensitive microelectrode arrays enabled by polymer pen
lithography.
AB - By combining polymer pen lithography (PPL) patterning with in situ
polymerization, we report a straightforward and bottom-up approach for bench-top
fabrication of microelectrode arrays (MEAs) with well-controlled dimensions. The
as-fabricated MEAs can be used to electrodeposit prussian blue in situ and work
as a biosensor for H2O2 with a detection limit as low as 5 nM at a sensitivity of
0.7 A cm-2 M-1.
PMID- 28492666
TI - DNA-friendly Cu(ii)/TEMPO-catalyzed 5-hydroxymethylcytosine-specific oxidation.
AB - The mixture of copper(ii) perchlorate and 2,2,6,6-tetramethylpiperidine-1-oxyl
(TEMPO) mildly and specifically oxidized 5-hydroxymethylcytosine to yield 5
formylcytosine because of its allyl alcohol specificity. The genomic DNA oxidized
at 5-hydroxymethylcytosine by the copper(ii)/TEMPO oxidation was efficiently
analyzed using various practical methods: DNA cleavage by piperidine, specific
functionalization by hydrazone formation, and genome-wide high-resolution
microarray.
PMID- 28492670
TI - Dietary krill oil enhances neurocognitive functions and modulates proteomic
changes in brain tissues of d-galactose induced aging mice.
AB - The effects of dietary krill oil on neurocognitive functions and proteomic
changes in brain tissues of d-galactose-induced aging mice were evaluated.
Dietary krill oil enhanced the neurocognitive functions of aging mice with a
significant (P < 0.05) decrease in escape latency and an increase in the number
of times of crossing over the hidden platform during the Morris water maze test.
Krill oil was also found to protect against oxidative damage, lipid peroxidation
and neurodegenerative diseases. Oxidative stress biomarkers of aging mice
administered with krill oil showed significant (P < 0.05) improvement with an
increase in serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)
levels; there were insignificant changes in the serum malondialdehyde (MDA)
level. In terms of proteomic changes, krill oil resulted in upregulation of the
Celsr3 and Ppp1r1b gene expression, which contribute to brain development,
learning and memory behavior processes. In particular, the Ppp1r1b gene is
associated with the inhibition of dopamine releases, which decreases the
motivation for learning.
PMID- 28492674
TI - A phenazine-barbituric acid based colorimetric and ratiometric near-infrared
fluorescent probe for sensitively differentiating biothiols and its application
in TiO2 sensor devices.
AB - A new colorimetric and ratiometric near-infrared fluorescent probe based on
phenazine-barbituric acid was developed to ultrasensitively detect biothiols. The
favorable ratiometric changes helped the imaging and differentiation of Cys in
living cells. Besides, the probe was successfully employed to construct TiO2
sensor devices, which could quantify Hcy concentration in serum.
PMID- 28492676
TI - A programmed terminal extension strategy to light up multiple beacons for DNA and
cellular telomerase detection.
AB - Here we develop a new method for the sensitive detection of DNA and cellular
telomerase using an enzyme-triggered terminal extension strategy that the
produced strand can light up multiple beacons on the surface of gold
nanoparticles.
PMID- 28492680
TI - Rare event simulations reveal subtle key steps in aqueous silicate condensation.
AB - A replica exchange transition interface sampling (RETIS) study combined with Born
Oppenheimer molecular dynamics (BOMD) is used to investigate the dynamics,
thermodynamics and the mechanism of the early stages of the silicate condensation
process. In this process, two silicate monomers, of which one is an anionic
species, form a negatively charged five-coordinated silicate dimer. In a second
stage, this dimer can fall apart again, forming the original monomers, or release
a water molecule into the solution. We studied the association and dissociation
reaction in the gas phase, and the dissociation and water removal step in the
aqueous phase. The results on the aqueous phase dissociation suggest two possible
mechanisms. The breakage of the bond between the intermediate oxygen and the five
coordinated silicon is sometimes accompanied by a proton transfer. After
dissociation into silicate monomers, the anionic monomer is either the previously
four-coordinated silicon or the previously five-coordinated silicon depending on
whether the hydrogen transfer occurs or not. Our results show that the mechanism
of proton transfer is highly predominant. Water removal simulations also show two
possible mechanisms distinguished by the proton transfer reaction path. Proton
transfer can occur either via a direct or via a water mediated reaction step. The
calculations reveal that although both mechanisms contribute to the water removal
process, the direct proton transfer is slightly favorable and occurs roughly in
six out of ten occasions.
PMID- 28492681
TI - Statistical modelling and simulation of nanohybrid shish-kebab architecture of PE
b-PEG copolymers and carbon nanotubes.
AB - Carbon nanotubes have been known to develop hierarchically ordered polymer
nanocomposites by virtue of epitaxial crystallization. A unique product of CNT
induced crystallization is generation of nanohybrid shish-kebab (NHSK) structure,
which has gained tremendous attention owing to its unique applications. However,
research faces major challenges in terms of producing tunable patterns on CNTs,
which are largely governed by precise control of the crystallization parameters.
Conventional methods of experimentation can mislead the effect of experimental
conditions on NHSK structure. The effect of crystallization time, undercooling
temperature and polymer concentration on the NHSK architecture of carbon
nanotubes (CNTs) and on a block copolymer, polyethylene-b-polyethylene glycol (PE
b-PEG), was studied in this work by applying the Response Surface Methodology
(RSM). The present novel investigation mainly reports the statistical models that
can be used to predict the different NHSK structural features such as diameter,
periodicity, and thickness by including the interaction and quadratic effects of
experimental variables. The developed models are in very good agreement with the
experimental data and are statistically significant. Our novel approach can be
used to better understand the interplay between various crystallization
parameters for periodic patterning on carbon nanotubes to generate tunable
hierarchical structures.
PMID- 28492682
TI - Scaling description of non-local rheology.
AB - The plastic flow of amorphous materials displays non-local effects, characterized
by a cooperativity length scale xi. We argue that these effects enter in the more
general description of surface phenomena near critical points. Using this
approach, we obtain a scaling relation between exponents that describe the strain
rate profiles in shear driven and pressure driven flow, which we confirm both in
numerical models and experimental data. We find empirically that the cooperative
length follows closely the characteristic length previously extracted in
homogenous bulk flows. This analysis shows that the often used mean field
exponents fail to capture quantitatively the non-local effects. Our analysis also
explains the unusually large finite size effects previously observed in pressure
driven flows.
PMID- 28492684
TI - Oxidative remediation of 4-methylcyclohexanemethanol (MCHM) and propylene glycol
phenyl ether (PPh). Evidence of contaminant repair reaction pathways.
AB - A large spill of 4-methylcyclohexanemethanol (MCHM) and propylene glycol phenyl
ether (PPh) into the Elk River near Charleston, West Virginia on January 9, 2014
led to serious water contamination and public concerns about appropriate
remediation. To assess the feasibility of advanced oxidation processes (AOPs) for
remediation of waters contaminated with these compounds, we induced hydroxyl
radical (HO) reactions using time-resolved and steady-state radiolysis methods.
Detailed product analyses showed initial HO attack was at the benzene ring of
PPh, and occurred through H-atom abstraction reactions for MCHM. Pulse radiolysis
and steady state radiolysis experiments conducted using pure compound solutions,
mixtures of the compounds and real water solvents allowed us to obtain
mechanistic insights of hydroxyl radical attack and establish the fate of the
compounds using AOP remediation technologies. These results demonstrate that
hydroxyl radical induced oxidization of PPh can lead to "repair-type" reactions,
which regenerates this contaminant. The study further highlights the importance
of such counterproductive reactions for the quantitative estimate of the required
amount of oxidant in any large-scale treatment approaches.
PMID- 28492685
TI - Crystal chemistry of Mg substitution in NaMnPO4 olivine: concentration limit and
cation distribution.
AB - Metal ion substitution in phospho-olivines is an effective way to improve their
performance as electrode materials in lithium ion and alternative sodium ion
batteries. In this contribution, we examine in detail the crystal structure of Mg
substituted NaMnPO4. The preferential occupancy of the alkaline M1 position by
Mg2+ ions has been found for the first time - a phenomenon which appears to be
opposite to the case of Mg-substituted LiMnPO4, where Mg2+ and Mn2+ reside in the
M2 position. Mg solubility in NaMnPO4 is limited in the range of 0.10 < Mg/(Mg +
Mn) < 0.15 mole part. Mg-substituted NaMnPO4 is prepared at 200 degrees C by
ionic exchange reactions involving the participation of mixed dittmarite salts,
KMn1-xMgxPO4.H2O. The structural aspects of Mg substitution in NaMnPO4 are
studied by combination of powder X-ray diffraction using the Rietveld analysis
with IR and electron paramagnetic resonance spectroscopy. The morphologies of
precursors and target olivines are examined by means of SEM and EDS. In order to
understand the crystal chemistry of Mg-substituted NaMnPO4, we use solid
solutions between LiMnPO4 and LiMgPO4 as references. The reference compositions
of LiMn1-xMgxPO4 are prepared using the same KMn1-xMgxPO4.H2O precursors as in
the case of Mg-substituted NaMnPO4.
PMID- 28492687
TI - Packing arrangement of 13C selectively labeled sequence model peptides of Samia
cynthia ricini silk fibroin fibers studied by solid-state NMR.
AB - Samia cynthia ricini (S. c. ricini) is one of the wild silkworms. Their silk
fibroins have been paid attention as potentially valuable biomedical materials as
well as Bombyx mori silk fibroins, but detailed information on the packing
arrangement of the fibers is still not currently well understood at a molecular
level. In this study, 34 mer model peptides, GGAGGGYGGDGG(A)12GGAGDGYGAG with
different 13C labeled positions have been synthesized as a typical sequence of
the primary structure of S. c. ricini silk fibroins made up of tandemly repeated
sequences of polyalanine as the crystalline region and glycin-rich sequences as
the non-crystalline region. The heterogeneous structure was obtained from the
determination of the fraction of several conformations depending on the position
of the Ala residue by 13C cross polarization/magic angle spinning NMR. The
packing arrangement was studied by 13C dipolar assisted rotational resonance NMR
and packing in a staggered arrangement rather than a rectangular arrangement of
this peptide with an anti-parallel beta-sheet structure was clarified, which is
in good agreement with our previous report on the packing arrangement of (Ala)7
with an anti-parallel beta-sheet structure.
PMID- 28492688
TI - Low energy electron attenuation lengths in core-shell nanoparticles.
AB - A velocity map imaging spectrometer is used to measure photoemission from free
core-shell nanoparticles, where a salt core is coated with a liquid hydrocarbon
shell (i.e. squalane). By varying the radial thickness of the hydrocarbon shell,
electron attenuation lengths (EALs) are determined by measuring the decay in
photoemission intensity from the salt core. In squalane, electrons with kinetic
energy (KE) above 2 eV are found to have EALs of 3-5 nm, whereas electrons with
smaller KE (<2 eV) have significantly larger EALs of >15 nm. These results (in
the context of other energy-resolved EAL measurements) suggest that the energy
dependent behavior of low energy electrons is similar in dielectrics when KE > 2
eV. At this energy the EALs do not appear to exhibit strong energy dependence.
However, at very low KE (<2 eV), the EALs diverge and appear to be extremely
material dependent.
PMID- 28492689
TI - Interconnected LiCuVO4 networks with in situ Cu generation as high-performance
lithium-ion battery anode.
AB - Interconnected LiCuVO4 networks were synthesized through a facile surfactant
assisted approach. Detailed investigations on the lithium storage mechanism
manifest that metallic Cu nanoparticles are generated in situ during the first
discharge process and remain mostly intact in the following cycles, thereby
enhancing conductivity of the electrode. The interconnected networks with
submicron sized primary particles endow the LiCuVO4 with a large amount of active
sites and thus high capacitive charge storage. Benefiting from a peculiar
structure, the resultant interconnected LiCuVO4 networks deliver extraordinary
rate performance (216 mA h g-1 up to 10 A g-1) and ultralong cycling stability
(~85% capacity retention after 5000 cycles at 5 A g-1). The exceptional rate
performance and cycling stability show that the interconnected LiCuVO4 networks
possess great potential for lithium-ion batteries.
PMID- 28492690
TI - Coordination nanosheets (CONASHs): strategies, structures and functions.
AB - Nanosheets, which are two-dimensional polymeric materials, remain among the most
actively researched areas of chemistry and physics this decade. Generally,
nanosheets are inorganic materials created from bulk crystalline layered
materials and have fascinating properties and functionalities. An emerging
alternative is molecule-based nanosheets containing organic molecular components.
Molecule-based nanosheets offer great diversity because their molecular, ionic,
and atomic constituents can be selected and combined to produce a wide variety of
nanosheets. The present article focuses on coordination nanosheets (CONASHs), a
class of molecule-based nanosheets comprising organic ligand molecules and metal
ions/atoms in a framework linked with coordination bonds. Following the
Introduction, Section 2 describes CONASHs, including their definition, design,
synthetic procedures, and characterisation techniques. Section 3 introduces
various examples of CONASHs, and Section 4 explores their functionality and
possible applications. Section 5 describes an outlook for the research field of
CONASHs.
PMID- 28492691
TI - Binding groups for highly ordered SAM formation: carboxylic versus thiol.
AB - The structure of analogous SAMs chemisorbed on an Ag substrate via a -SH or -COOH
binding group is reported. Our observations indicate that COOH binding groups can
be considered as a promising alternative for the current standard based on the
sulfur binding groups, particularly when 2D ordering, SAM fabrication time and
stability under ambient conditions are of great importance.
PMID- 28492692
TI - Pharmacokinetics of table and Port red wine anthocyanins: a crossover trial in
healthy men.
AB - This study was designed to evaluate the pharmacokinetics of Port and table red
wine anthocyanins in healthy men. Volunteers were recruited to drink 250 mL of a
table red wine (221 mg of anthocyanins) and 150 mL of young Port red wine (49 mg
of anthocyanins). Venous blood was collected from participants at 0, 15, 30, 60
and 120 min after wine ingestion. Urine samples were collected at baseline and at
120 min. Anthocyanins and anthocyanin metabolites in plasma and urine samples
were quantified by HPLC-DAD and tentatively identified by LC-MS. Red wine
anthocyanins were detected in their intact forms in both plasma and urine
samples, but the glucuronylated metabolites of peonidin and malvidin (PnGlucr and
MvGlucr) were the two main derivatives detected after both red wine consumptions.
For the first time, and supported by the synthesis of Mv3Glucr, the main pathway
followed by Mv3glc after absorption was described and involves anthocyanidin
conjugation with glucuronic acid after glucose removal. Despite the lower total
content of anthocyanins ingested when volunteers drank Port wine, no differences
were observed in the plasma Cmax of MvGlucr and PnGlucr after table and Port red
wine consumption. The relative bioavailability of anthocyanins in Port wine was
96.58 +/- 5.74%, compared to the anthocyanins present in red wine. In conclusion,
both Port and table red wines are good sources of bioavailable anthocyanins.
PMID- 28492693
TI - Nickel catalyzed enantioselective hydroarsination of nitrostyrene.
AB - A catalytic asymmetric hydroarsination reaction of an activated alkene viz. (E)
nitrostyrene was developed using chiral PCP Pt-, Pd- and Ni-pincer complexes as
catalysts. The corresponding chiral tertiary arsine adduct was obtained in ees of
up to 80% under mild reaction conditions using the PCP Ni-Cl pincer catalyst. The
arsine adduct was furnished with catalyst loadings of 1-5 mol% and the reaction
duration ranging from <5 min to 180 min. The subsequent coordination of the
hydroarsination product to gold(i) chloride allowed for the confirmation of the
stereochemistry of the arsine adduct via crystallographic analysis.
PMID- 28492694
TI - Tuning the electronic properties of monolayer and bilayer transition metal
dichalcogenide compounds under direct out-of-plane compression.
AB - The band-gap modulation of atomically thin semiconductor transition metal
dichalcogenides (MX2; M = Mo or W, X = S or Se) under direct out-of-plane
compression is systematically studied by means of the density functional theory
(DFT) formalism including spin-orbit coupling (SOC) and dispersion correction
(D3). The out-of-plane compared with other regimes stress regime significantly
reduces the pressure threshold at which the semimetal state is achieved (2.7-3.1
and 1.9-3.2 GPa for mono- and bilayer systems, respectively). Structural,
electronic and bonding properties are investigated for a better understanding of
the electronic transitions achieved with compression. A notable relationship with
the formal ionic radius (M4+ and X2-) is obtained. On one hand, the monolayer
systems with the smallest transition metal radius (Mo4+ < W4+) reach the
semimetal state at lower stress, on the other hand, for bilayer specimens the
transition to semimetal is observed earlier for compounds with the smallest
chalcogenide radius (S2- < Se2-). Moreover, the appearance of non-covalent
interaction (NCI) domains in the semimetal state confirms that the out-of-plane
compression promotes the interaction between sulfur atoms in the single layered
systems and reduces the interlayer space in bilayer configurations. Our
predictions, supported by experimental evidences in the case of monolayered MoS2,
demonstrate new alternative methods for tuning the electronic properties of
transition metal dichalcogenides under direct out-of-plane compression.
PMID- 28492695
TI - Joint assessment in von Willebrand disease. Validation of the Haemophilia Joint
Health score and Haemophilia Activities List.
AB - Assessment of clinical outcome after joint bleeding is essential to identify
joint damage and optimise treatment, to prevent disability. However, disease
specific tools to assess the musculoskeletal status in patients with von
Willebrand disease (VWD) are lacking. We aimed to determine validity and
reliability of the Haemophilia Joint Health Score (HJHS) and Haemophilia
Activities List (HAL) in patients with Von Willebrand disease (VWD). Ninety-six
patients with VWD were included (mean age 46 years) of whom 27 had more than five
documented joint bleeds. The HJHS was performed in all patients and all patients
completed the HAL and Impact on Participation and Autonomy (IPA) questionnaires.
Health-related quality of life (SF36) results were obtained from the prior
'Willebrand in the Netherlands' study. Joint X-rays of knees, elbows and ankles
were scored according to Pettersson (PS). Internal consistency of the HJHS
(Cronbach's alpha (alpha)=0.75) and HAL (alpha=0.89) were good. Inter-observer
agreement of the HJHS was good (ICC 0.84; Limits of Agreement +/- 10.3). The HJHS
showed acceptable correlation with the X-ray PS (Spearman's r (rs)>0.60 all
joints) and HAL (rs=0.71). The HAL also showed acceptable correlation with the
SF36 physical functioning (rs=0.65) and IPA (rs=0.69). Hypothesis testing showed
adequate discriminative power of both instruments: in patients with a history of
>5 versus <= 5 joint bleeds (median HJHS 10 vs 2 (p<0.01); median HAL 77 vs 98
(p<0.01)), independent from age. In conclusion, both the HJHS and HAL are
feasible to assess clinical outcome after joint bleeds in VWD.
PMID- 28492696
TI - Complex recombination with deletion in the F8 and duplication in the TMLHE
mediated by int22h copies during early embryogenesis.
AB - Haemophilia A (HA) is a common X-linked recessive bleeding disorder and almost
one half of patients with severe HA are caused by intron 22 inversion (Inv22) in
the F8. Inv22 is considered to be almost exclusively of meiotic origin in germ
cells during spermatogenesis and only one mosaic Inv22 female carrier with the
mutation possibly occurring during mitosis of the embryo has been reported so
far. Previously we have identified a novel complex recombination mediated by
int22h copies in a sporadic severe HA pedigree and herein we have localised the
sequences flanking the breakpoint region using genome walking technique, AccuCopy
technique, gene chip and real-time PCR. The disease causing genetic variant
registered an 18.1 kb deletion including part of int22h-1 through the intron 23
of F8 and a 113.3 kb duplication of part of int22h-2 through the intron 1 of
TMLHE inserted in the religated region of the F8. Two intrinsically linked
mechanisms of recombination-dependent DNA replication: microhomology-mediated
break-induced replication (MMBIR) followed by break-induced replication (BIR)
might be responsible for the incident of the complex recombination during early
embryogenesis of the proband's mother.
PMID- 28492697
TI - CD32 inhibition and high dose of rhFVIII suppress murine FVIII-specific recall
response by distinct mechanisms in vitro.
AB - Development of neutralising antibodies (inhibitors) against factor VIII (FVIII)
is a frequent and severe complication of replacement therapy in haemophilia A.
Previous data from haemophilia A mouse model demonstrates that both CD32
inhibition and high doses of rhFVIII prevent the differentiation of FVIII
specific memory B cells (MBCs) into antibody secreting cells (ASCs). Here,
cellular targets responsible for the suppression of ASC formation by means of
CD32 inhibition and high dose of rhFVIII were analysed. We investigated apoptosis
on FVIII-specific MBCs using a pan caspases inhibitor, and screened for defects
in rhFVIII presentation by analysing T cell release of Th1- and Th2-cytokines in
vitro. Although high dose of rhFVIII suppressed ASC formation, cytokine response
was not affected. Upon re-stimulation of splenocytes with high dose of rhFVIII,
prevention of apoptosis fully restored the FVIII-specific recall response. In
contrast, genetic deletion or inhibition of CD32 significantly altered Th1- and
Th2-response. CD32 blockade and inhibition of apoptosis resulted in a partial
rescue of FVIII-specific ASCs. Normal cytokine secretion could not be restored.
In conclusion, suppression of FVIII-specific recall response by CD32 and high
doses of rhFVIII is mediated by distinct mechanisms. High dose of rhFVIII induces
apoptosis in FVIII-specific MBCs but does not influence FVIII-specific T cell
response. CD32 blockade, however, may suppress the FVIII-specific recall response
by two ways: i) increasing apoptosis of FVIII-specific MBCs and ii) disturbing
FVIII-specific T cell response by modulating presentation of rhFVIII to CD4+ T
cells in vitro.
PMID- 28492698
TI - IL-33 stimulates the release of procoagulant microvesicles from human monocytes
and differentially increases tissue factor in human monocyte subsets.
AB - Monocytes and monocyte-derived microvesicles (MVs) are the main source of
circulating tissue factor (TF). Increased monocyte TF expression and increased
circulating levels of procoagulant MVs contribute to the formation of a
prothrombotic state in patients with cardiovascular disease. Interleukin (IL)-33
is a pro-inflammatory cytokine involved in atherosclerosis and other inflammatory
diseases, but its role in regulating thrombosis is still unclear. The aim of the
present study was to investigate the effects of IL-33 on the procoagulant
properties of human monocytes and monocyte-derived MVs. IL-33 induced a time- and
concentration-dependent increase of monocyte TF mRNA and protein levels via
binding to the ST2-receptor and activation of the NF-kappaB-pathway. The IL-33
treated monocytes also released CD14+TF+ MVs and IL-33 was found to increase the
TF activity of both the isolated monocytes and monocyte-derived MVs. The
monocytes were classified into subsets according to their CD14 and CD16
expression. Intermediate monocytes (IM) showed the highest ST2 receptor
expression, followed by non-classical monocytes (NCM), and classical monocytes
(CM). IL-33 induced a significant increase of TF only in the IM (p<0.01), with a
tendency in NCM (p=0.06), but no increase was observed in CM. Finally, plasma
levels of IL-33 were positively correlated with CD14+TF+ MVs in patients
undergoing carotid endarterectomy (r=0.480; p=0.032; n=20). We hereby provide
novel evidence that the proinflammatory cytokine IL-33 induces differential TF
expression and activity in monocyte subsets, as well as the release of
procoagulant MVs. In this manner, IL-33 may contribute to the formation of a
prothrombotic state characteristic for cardiovascular disease.
PMID- 28492699
TI - Lipopolysaccharide as trigger of platelet aggregation via eicosanoid over
production.
AB - The effect of lipopolysaccharide (LPS) on platelet aggregation is still
controversial. We performed in vitro and ex vivo studies in controls and in
patients with community-acquired pneumonia (CAP) to assess the effect of LPS on
platelet activation (PA). LPS (15-100 pg/ml) significantly increased PA only if
combined with sub-threshold concentrations (STC) of collagen or ADP; this effect
was associated with increased platelet H2O2 production, Nox2 activation, PLA2
phosphorylation, thromboxane (Tx)A2 and 8-iso-PGF2alpha-III, and was inhibited by
aspirin, TxA2 receptor antagonist or by Toll-like receptor 4 blocking peptide
(TLR4bp). Analysis of up-stream signalling potentially responsible for Nox2 and
PLA2 activation demonstrated that LPS-mediated PA was associated with
phosphorylation of AKT, p38 and p47phox translocation. In 10 consecutive CAP
patients serum endotoxins were significantly higher compared to 10 controls (145
[115-187] vs 18 [6-21] pg/ml; p<0.01). Ex vivo study showed that agonist
stimulated platelets were associated with enhanced PA (p<0.01), Toll-like
receptor 4 (TLR4) expression (p<0.05), TxA2 (p<0.01) and 8-iso-PGF2alpha-III
(p<0.01) production in CAP patients compared to controls. The study provides
evidence that LPS amplifies the platelet response to common agonists via TLR4
mediated eicosanoid production and suggests LPS as a potential trigger for PA in
CAP.
PMID- 28492700
TI - Coagulation factor XI improves host defence during murine pneumonia-derived
sepsis independent of factor XII activation.
AB - Bacterial pneumonia, the most common cause of sepsis, is associated with
activation of coagulation. Factor XI (FXI), the key component of the intrinsic
pathway, can be activated via factor XII (FXII), part of the contact system, or
via thrombin. To determine whether intrinsic coagulation is involved in host
defence during pneumonia and whether this is dependent on FXII activation, we
infected in parallel wild-type (WT), FXI knockout (KO) and FXII KO mice with two
different clinically relevant pathogens, the Gram-positive bacterium
Streptococcus pneumoniae and the Gram-negative bacterium Klebsiella pneumoniae,
via the airways. FXI deficiency worsened survival and enhanced bacterial
outgrowth in both pneumonia models. This was accompanied with enhanced
inflammatory responses in FXI KO mice. FXII KO mice were comparable with WT mice
in Streptococcus pneumoniae pneumonia. On the contrary, FXII deficiency improved
survival and reduced bacterial outgrowth following infection with Klebsiella
pneumoniae. In both pneumonia models, local coagulation was not impaired in
either FXI KO or FXII KO mice. The capacity to phagocytose bacteria was impaired
in FXI KO neutrophils and in human neutrophils where activation of FXI was
inhibited. Deficiency for FXII or blocking activation of FXI via FXIIa had no
effect on phagocytosis. Taken together, these data suggest that FXI protects
against sepsis derived from Streptococcus pneumoniae or Klebsiella pneumoniae
pneumonia at least in part by enhancing the phagocytic capacity of neutrophils by
a mechanism that is independent of activation via FXIIa.
PMID- 28492701
TI - Short-term intensive training attenuates the exercise-induced interaction of mono
1/2 cells and platelets after coronary bypass in cardiac patients.
AB - The interaction between platelets and monocytes plays a critical role in the
pathogenesis and progression of cardiovascular diseases. This study investigated
how short-term intensive training (SIT) influences monocyte subset
characteristics and exercise-induced monocyte and platelet aggregates (MPAs)
following elective coronary bypass (CABG) in cardiac patients. Forty-nine
patients hospitalised for CABG were randomised into SIT (N=26) and conventional
training (CT, N=23) groups. The SIT subjects underwent supervised aerobic
training at 80~120 % of the ventilatory anaerobic threshold based on sub-maximal
exercise tests performed 7 days post-CABG for 20 sessions with two sessions/day
and 30 min/session, which were completed within four weeks after surgery. The CT
subjects performed light-intensity conditioning exercise for <=4 sessions.
Resting and maximal exercise-mediated monocyte characteristics and MPA were
determined before and following intervention. The SIT group had a larger
improvement in ventilation efficiency and anaerobic threshold than the CT group;
the SIT group exhibited larger reductions in blood monocyte subtypes 1 and 2
(Mono1 and 2) counts at rest than the CT group; the SIT group but not the CT
group exhibited attenuated formation of Mono1/platelet hetero-aggregation (MPA1)
and CD42b expression on Mono1/2 caused by strenuous exercise; and plasma levels
of macrophage inflammatory protein-1beta and soluble P-selectin showed similar
trends as Mono1/2 and MPA1, respectively. In conclusion, SIT modestly improved
aerobic capacity in patients following CABG. Moreover, SIT simultaneously
ameliorated the CD42b expression of Mono1/2 cells and maximal exercise-induced
MPA1, which may reduce the risk of inflammatory thrombosis.
PMID- 28492702
TI - Low plasma FVII:C and activated FVII as predictive markers for overt disseminated
intravascular coagulation.
AB - In sepsis, binding of factor VII (FVII:C) and activated factor VII (FVIIa) with
tissue factor is the key step of coagulation resulting in disseminated
intravascular coagulation (DIC). We conducted a prospective cohort study among 47
septic patients, aged 8 months to 18.8 years. They were initially divided into
three groups of no DIC (n=27), non-overt DIC (n=14) and overt DIC (n=6). Blood
samples were collected at 0, 24 and 48 hours (h) after the onset of sepsis. At
the onset of sepsis, FVII:C tended to be lower in the non-overt DIC [median 57 %
(interquartile range [IQR] 41-80)] and overt DIC groups [33 % (23-52)] than that
in the no DIC group [65 % (44-87)]. Whereas FVIIa tended to be lower in the overt
DIC group [1.29 % (0.50-4.19)] than those in the non-overt DIC [3.01 % (1.01
5.24)] and no DIC groups [2.49 % (1.14-3.13)]. At 24 h, FVII:C was significantly
lower in the non-overt DIC [57 % (41-101)] and overt DIC groups [31 % (28-49)]
than that in the no DIC group [83 % (70-102)]. While FVIIa was significantly
lower in the overt DIC group [2.15 % (0.86-3.96)] than that in the no DIC group
[3.83 % (2.90-5.46)]. Using FVII:C <65 % or FVIIa <3 % at 24 h among patients
without hepatic dysfunction to determine overt DIC at 24 h, the sensitivity was
83.9 % and 77.4 %, respectively, and the specificity was both 83.3 %. Patients
with low FVII:C and low FVIIa at 24 h after the onset of sepsis had a 20.8-fold
(95 % confidence interval [CI], 2.0-213.0, p=0.010) and 14.4-fold (95 %CI, 1.5
142.4, p=0.023) chance of overt DIC.
PMID- 28492703
TI - Prehispanic (Guanches) mummies and natrium salts in burial caves of Las Canadas
del Teide (Tenerife).
AB - ABSTRACT: The prehispanic population of Tenerife (Guanches) buried their dead in
caves. Many corpses are totally or partially mummified. Embalming procedures are
largely unknown, besides some information recorded by chroniclers and the general
idea that environmental conditions in some areas may favour natural
mummification. Detailed observation of burial caves containing mummified corpses
revealed the presence of a white mineral in form of crusts or powder that was not
present in the vast majority of non-burial caves, especially in basaltic and
trachybasaltic lava flows. We analysed these crusts and they consist of natrium
carbonate salts. Therefore, we conducted a search visiting 30 caves, 3 of them
harbouring mummified corpses, and made analyses if there were natrium salts in
these caves and their amount. One burial cave was located in trachyphonolitic
lava flow, and two further caves in trachybasaltic and basaltic lava flows. There
was a significant association between presence of natrium salts and use of the
cave as a burial site (chi2 = 9.37; p = 0.0259). The semiquantitatively assessed
amount of natrium salts was also by far higher in burial caves than in non-burial
ones (Z = 2.58, p = 0.01). There are no reports that support the use of natrium
salts in the embalming process among the Guanches, but we found a clear-cut
relationship between the presence and/or amount of natrium salts in caves and
their use as burial sites by the prehispanic population buried in the central
highlands, suggesting an intentional use of caves containing this mineral as
burial caves, based perhaps on the observation of the ability of natrium salts to
preserve corpses.
PMID- 28492704
TI - Effectiveness of a school-based intervention to reduce the prevalence of
overweight and obesity in children aged 7-11 years from Poznan (Poland).
AB - ABSTRACT: The epidemic of obesity, which is one of the most important public
health problems, appeared paradoxically as a result of improving living
conditions. The aim of this study was to determine the effects on
overweight/obesity prevalence of the primary-school-based intervention program.
The group of 5,293 children (7-11 year-olds) from Poznan (Poland) was divided
into two subgroups: experimental and control one. The research group was
participating in extra physical activities. Measurements (height and weight) were
taken twice: at baseline and after 1-year follow-up. The estimations of the
prevalence of overweight/obesity were based on the cut-off points of the IOTF
values. To estimate the risk the odds ratio (OR) were calculated. There were no
differences in BMI for both boys and girls. Also there were no significant
differences in prevalence of overweight and obesity, for both sexes. The risk of
being overweight/obese was not reduced in children in the experimental group - OR
for boys was 0.93 (0.80, 1.08), and for girls OR = 0.88 (0.76, 1.03). In
conclusion, the risk of overweight/obesity has not changed after one year of
extra physical activities and engagement in health-oriented education program.
This study shows that in case of such programs it is necessary to apply more
intense interventions, probably also during longer period of time. It is possible
that other adverse factors have a stronger influence on the body mass, which
would suggest that the theoretical part of intervention concerning pro-health
related behaviors was not implemented in practice.
PMID- 28492705
TI - Race, health, and discrimination: historical and contemporary perspectives from
Brazil and the United States.
PMID- 28492706
TI - Confronting racism in health services.
PMID- 28492707
TI - The strangest of all encounters: racial and ethnic discrimination in US health
care.
AB - In 2003, a Committee of the Institute of Medicine of the National Academy of
Sciences summarized hundreds of studies documenting that US racial minorities,
especially African Americans, receive poorer quality health care for a wide
variety of conditions than their White counterparts. These racial differences in
health care persist after controlling for sociodemographic factors and patients'
ability to pay for care. The Committee concluded that physicians' unconscious
negative stereotypes of African Americans, and perhaps other people of color,
likely contribute to these health care disparities. This paper selectively
reviews studies published after 2003 on the likely contribution of physicians'
unconscious bias to US health care disparities. All studies used the Implicit
Association Test which quantifies the relative speed with which individuals
associate positive attributes like "intelligent" with Whites compared to Blacks
or Latino/as. In addition to assessing physicians' unconscious attitudes toward
patients, some studies focused on the behavioral and affective dimensions of
doctor-patient communication, such as physicians' "verbal dominance" and whether
patients felt respected. Studies reviewed found a "pro-white" unconscious bias in
physicians' attitudes toward and interactions with patients, though some evidence
suggests that Black and female physicians may be less prone to such bias. Limited
social contact between White physicians and racial/ethnic minorities outside of
medical settings, plus severe time pressures physicians often face during
encounters with patients who have complex health problems could heighten their
susceptibility to unconscious bias.
PMID- 28492708
TI - Shadows of doubt: the uneasy incorporation of identification science into legal
determination of paternity in Brazil.
AB - The arrival of DNA paternity testing in the 1980s was met with great enthusiasm
in the Brazilian courts. Yet, over the past two decades, Brazilian legal doctrine
and jurisprudence have increasingly rejected DNA proof as the sine qua non for
paternity cases. Instead, DNA paternity testing has generated mountains of
litigation, as biological proof has been challenged by the argument that
paternity is primarily "socio-affective". Leading family law specialists describe
this new conception of paternity as an outcome of the "revolutionary" provisions
of the 1988 Constitution, which recognizes the "pluralism" of family forms in
modern society and guarantees equal family rights for all children. Without
denying the significance of the constitution's dignitary framework, we show that
new legal understandings of paternity represent less a paradigm shift than a
continuation of longstanding historical tensions between biological and socio
cultural understandings of family and identity. In this article, we explore the
development of biological and eventually genetic typing in Brazil, both of which
had ties to the fields of criminology and race science. Our review suggests that
techniques of biological identification, no matter how sophisticated or precise,
were ineffective means for establishing identity, whether of individual
personhood, as in the case of paternity, or national make-up. Instead, they
became incorporated as supplemental methods into complex legal, social, and
cultural decision-making around families.
PMID- 28492709
TI - Differential reporting of discriminatory experiences in Brazil and the United
States.
AB - There has been little cross-national comparison of perceived discrimination, and
few studies have considered how intersectional identities shape perception of
discriminatory treatment in different societies. Using data from the ELSA-Brasil,
a study of Brazilian civil servants, and the Americans' Changing Lives Study, a
nationally-representative sample of U.S. adults, we compare reports of lifetime
discrimination among race-by-gender groups in each society. We also consider
whether educational attainment explains any group differences, or if differences
across groups vary by level of education. Results reveal higher lifetime
discrimination experiences among Black respondents in both countries, especially
Black men, than among Whites, and lower reports among White women than White men.
Brown men and women also reported higher levels than White men in Brazil. For all
race-by-gender groups in both countries, except Brazilian White men, reports of
discrimination were higher among the more educated, though adjusting for
educational differences across groups did not explain group differences. In
Brazil, we found the greatest racial disparities among the college educated,
while U.S. Black men were more likely to report discrimination than White men at
all levels of education. Results reveal broad similarities across countries,
despite important differences in their histories, and an intersectional approach
contributed to identification of these similarities and some differences in
discrimination experiences. These findings have implications for social and
public health surveillance and intervention to address the harmful consequences
of discrimination.
PMID- 28492710
TI - Race and U.S. medical experimentation: the case of Tuskegee.
PMID- 28492711
TI - CURCUMIN IN COMBINATION WITH TRIPLE THERAPY REGIMES AMELIORATES OXIDATIVE STRESS
AND HISTOPATHOLOGIC CHANGES IN CHRONIC GASTRITIS-ASSOCIATED HELICOBACTER PYLORI
INFECTION.
AB - BACKGROUND: Helicobacter pylori (H. pylori) gastric infection is a main cause of
inflammatory changes and gastric cancers. OBJECTIVE: The aim of this study was
finding the effects of curcumin on oxidative stress and histological changes in
chronic gastritis associated with H. pylori. METHODS: In a randomized clinical
trial, patients were divided into two groups: a standard triple therapy group and
triple therapy with curcumin group. Endoscopic and histological examinations were
measured for all patients before and after 8 weeks. RESULTS: Triple therapy with
curcumin treatment group significantly decreased malondialdehyde markers,
glutathione peroxides and increased total antioxidant capacity of the gastric
mucosa at the end of study compared to baseline and triple regimen groups. In
addition, the oxidative damage to DNA was significantly decreased in triple
therapy with curcumin group at the end of study compared to baseline and compared
to triple therapy (P<0.05 for both). Triple therapy group in combination with
Curcumin significantly decreased all active, chronic and endoscopic inflammation
scores of patients compared to the baseline and triple therapy group (P<0.05 for
both). The eradication rate by triple therapy + curcumin was significantly
increased compared to triple therapy alone (P<0.05). CONCLUSION: Curcumin can be
a useful supplement to improve chronic inflammation and prevention of
carcinogenic changes in patients with chronic gastritis associated by H. pylori.
PMID- 28492712
TI - LUGOL'S IODINE CHROMOENDOSCOPY VERSUS NARROW BAND IMAGE ENHANCED ENDOSCOPY FOR
THE DETECTION OF ESOPHAGEAL CANCER IN PATIENTS WITH STENOSIS SECONDARY TO
CAUSTIC/CORROSIVE AGENT INGESTION.
AB - BACKGROUND: The diagnosis of corrosion cancer should be suspected in patients
with corrosive ingestion if after a latent period of negligible symptoms there is
development of dysphagia, or poor response to dilatation, or if respiratory
symptoms develop in an otherwise stable patient of esophageal stenosis. Narrow
Band Imaging detects superficial squamous cell carcinoma more frequently than
white-light imaging, and has significantly higher sensitivity and accuracy
compared with white-light. OBJECTIVE: To determinate the clinical applicability
of Narrow Band Imaging versus Lugol's solution chromendoscopy for detection of
early esophageal cancer in patients with caustic/corrosive agent stenosis.
METHODS: Thirty-eight patients, aged between 28-84 were enrolled and examined by
both Narrow Band Imaging and Lugol's solution chromendoscopy. A 4.9mm diameter
endoscope was used facilitating examination of a stenotic area without dilation.
Narrow Band Imaging was performed and any lesion detected was marked for later
biopsy. Then, Lugol's solution chromoendoscopy was performed and biopsies were
taken at suspicious areas. Patients who had abnormal findings at the routine,
Narrow Band Imaging or Lugol's solution chromoscopy exam had their stenotic ring
biopsied. RESULTS: We detected nine suspicious lesions with Narrow Band Imaging
and 14 with Lugol's solution chromendoscopy. The sensitivity and specificity of
the Narrow Band Imaging was 100% and 80.6%, and with Lugol's chromoscopy 100% and
66.67%, respectively. Five (13%) suspicious lesions were detected both with
Narrow Band Imaging and Lugol's chromoscopy, two (40%) of these lesions were
confirmed carcinoma on histopathological examination. CONCLUSION: Narrow Band
Imaging is an applicable option to detect and evaluate cancer in patients with
caustic /corrosive stenosis compared to the Lugol's solution chromoscopy.
PMID- 28492713
TI - FLAVONOIDS AND ANTI-OXIDANT ACTIVITY MEDIATED GASTROPROTECTIVE ACTION OF LEATHERY
MURDAH, TERMINALIA CORIACEA (ROXB.) WIGHT & ARN. LEAF METHANOLIC EXTRACT IN RATS.
AB - BACKGROUND: Leathery Murdah, Terminalia coriacea (Roxb.) Wight & Arn. from family
Combretaceae is used in Ayurveda and Siddha traditional systems of medicine to
heal ulcers. OBJECTIVE: The present study was conducted to assess the
gastroprotective effect and understand the fundamental mechanism of action of
Leathery Murdah, Terminalia coriacea (Roxb.) Wight & Arn. Leaf Methanolic
Extract. METHODS: The test extract was screened for anti-ulcer activity by
Aspirin induced ulcerogenesis in pyloric ligation and ethanol induced gastric
ulcers at three doses - 125, 250, and 500 mg/kg, p.o. using Ranitidine 50 mg/kg
and Misoprostol 100 MUg/kg as standard drug in respective models. Seven
parameters were carefully examined, that is, ulcer index, total protein, mucin,
catalase, malondialdehyde, and superoxide dismutase levels and histopathology.
High Performance Liquid Chromatographic - Ultra Violet profiling and Liquid
Chromatography - Mass Spectral analysis of crude Terminalia coriacea leaves
methanolic extract were carried out as a part of chemical characterization to
identify bioactive compounds. RESULTS: All the test doses exhibited significant
gastroprotective function, particularly the higher doses demonstrated improved
action. The results revealed a significant increase in the levels of catalase,
superoxide dismutase, and Mucin with reduction in ulcer index, the levels of
total protein, and malondialdehyde. Histopathological observations also
illustrated the gastroprotective effect of Terminalia coriacea leaves methanolic
extract. CONCLUSION: Terminalia coriacea leaves methanolic extract exhibited
strong anti-oxidant and anti-secretory activities mediated gastroprotection
besides inducing the gastric mucosal production. The observed pharmacological
response can be attributed to the flavonoidal compounds namely - Quercetin-3-O
rutinoside, Luteolin-7-O-glucoside, Myricetin hexoside, Quercetin-3-O-glucoside,
Isorhamnetin-3-O-rhamnosylglucoside and Isorhamnetin-3-O-glucoside identified in
the extract for the first time with High Performance Liquid Chromatographic -
Ultra Violet and Liquid Chromatography - Mass Spectral analysis.
PMID- 28492714
TI - MAST CELLS DISTINGUISH EOSINOPHILIC ESOPHAGITIS IN PEDIATRIC PATIENTS.
AB - BACKGROUND: : Mast cells exert a substantial role in gastrointestinal allergic
diseases. Therefore, it is reasonable to presume that mast cell may aid diagnosis
in eosinophilic gastroenteropathy. OBJECTIVE: : To evaluate whether mast cell
count in the esophageal epithelium can discriminate eosinophilic esophagitis,
proton-pump inhibitor (PPI)-responsive eosinophilic esophagitis and
gastroesophageal reflux esophagitis. METHODS:: Retrospectively we reviewed the
files of 53 consecutive patients (age: 7.8 years; range: 8-14 years) with
definitive diagnose established during clinical follow up in a universitary
outpatient clinic as follow: eosinophilic esophagitis (N=23), PPI-responsive
eosinophilic esophagitis (N=15) and gastroesophageal reflux esophagitis (N=15).
Eosinophil count in the esophageal epithelium in slides stained with H-E was
reviewed and immunohistochemistry for mast cell tryptase was performed. RESULTS::
Count of eosinophils/high-power field (HPF) higher than 15 were found in 14 out
of 15 reflux esophagitis patients. The mean count of eosinophils/HPF was similar
in eosinophilic esophagitis patients and in those with PPI-responsive
eosinophilic esophagitis (42 and 39 eosinophils/HPF, respectively, P=0.47).
Values of mast cell tryptase (+) were higher in eosinophilic esophagitis [median:
25 mast cells/HPF; range (17-43) ] and in PPI-responsive eosinophilic esophagitis
patients [25 (16-32) ], compared to reflux esophagitis [4 (2-14) ], P<0.001.
There was no difference between the mean count of mast cells/HPF in the
esophageal epithelium of eosinophilic esophagitis patients and PPI-responsive
eosinophilic esophagitis patients, respectively, 26 and 24 mast cells/HPF,
P=0.391. CONCLUSION: : Tryptase staining of mast cells differentiates
eosinophilic esophagitis from reflux esophagitis.
PMID- 28492715
TI - MANIPULATION OF THE INTESTINAL MICROBIOTA: THE MEDICINE REVOLUTION OF THE 21ST
CENTURY.
PMID- 28492716
TI - Prevalence of phonological disorders and phonological processes in typical and
atypical phonological development.
AB - Purpose: To determine the occurrence of phonological disorders by age, gender and
school type, and analyze the phonological processes observed in typical and
atypical phonological development across different age groups. Methods: The
sample consisted of 866 children aged between 3:0 and 8:11 years, recruited from
public and private schools in the city of Santa Maria/RS. A phonological
evaluation was performed to analyze the operative phonological processes.
Results: 15.26% (n = 132) of the sample presented atypical phonological
acquisition (phonological disorders). Phonological impairments were more frequent
in public school students across all age groups. Phonological alterations were
most frequent between ages 4 -to 6, and more prevalent in males than females in
all but the youngest age group. The most common phonological processes in typical
phonological acquisition were: cluster reduction; nonlateral liquid deletion in
coda; nonlateral liquid substitution in onset; semivocalization of lateral
liquids in coda; and unstressed syllable deletion. In children with phonological
disorders, the most common phonological processes were: lateral and nonlateral
liquid substitution in onset position; nonlateral liquid deletion; fronting of
fricatives in onset position; unstressed syllable deletion; semivocalization of
nonlateral liquid in coda; and nonlateral liquid deletion in coda position.
Conclusion: Phonological processes were highly prevalent in the present sample,
and occurred more often in boys than in girls. Information regarding the type and
frequency of phonological processes in both typical phonological acquisition and
phonological disorders may contribute to early diagnosis and increase the
efficiency of treatment planning.
PMID- 28492717
TI - Endoscopic Ultrasonography in the Diagnosis and Treatment Strategy Choice of
Esophageal Leiomyoma.
AB - OBJECTIVES:: Esophageal leiomyoma is the most common benign tumor of the
esophagus, and it originates from mesenchymal tissue. This study analyzed the
clinicopathological characteristics of esophageal leiomyoma and aimed to evaluate
the role of endoscopic ultrasonography in the diagnosis and treatment selection
for these lesions. METHODS:: Two hundred and twenty-five patients who had
suspected esophageal leiomyomas in endoscopic ultrasonography were enrolled at
the Endoscopy Center of The First Affiliated Hospital, Zhejiang University from
January 1st, 2009 to May 31th, 2015. The main outcomes included the demographic
and morphological characteristics, symptoms, comparisons of diagnosis and
treatment methods, adverse events, and prognosis. RESULTS:: One hundred and sixty
seven patients were diagnosed as having an esophageal leiomyoma by pathological
examination. The mean patient age was 50.57+/-9.983 years. In total, 62.9% of the
lesions originated from the muscularis mucosa, and the others originated from the
muscularis propria. The median distance to the incisors was 30+/-12 cm. The
median diameter was 0.72+/-0.99 cm. As determined by endoscopic ultrasonography,
most existing leiomyomas were homogeneous, endophytic, and spherical. The
leiomyomas from the muscularis mucosa were smaller than those from the muscularis
propria and much closer to the incisors (p<0.05). SMA (smooth muscle antibody)
(97.2%) and desmin (94.5%) were positive in the majority of patients. In terms of
treatments, patients preferred endoscopic therapies, which led to less adverse
events (e.g., intraoperative bleeding, local infection, pleural effusion) than
surgical operations (p<0.05). The superficial leiomyomas presented less adverse
events and better recovery (p<0.05) than deep leiomyomas. CONCLUSION:: Endoscopic
ultrasonography has demonstrated high accuracy in the diagnosis of esophageal
leiomyomas and provides great support in selecting treatments; however, EUS
cannot completely avoid misdiagnosis, so combining it with other examinations may
be a good strategy to solve this problem.
PMID- 28492718
TI - Effects of Motor Learning on Clinical Isokinetic Test Performance in Knee
Osteoarthritis Patients.
AB - OBJECTIVES:: To analyze the effects of motor learning on knee extension-flexion
isokinetic performance in knee osteoarthritis patients. METHODS:: One hundred and
thirty-six middle-aged and older sedentary individuals (111 women, 64.3+/-9.9
years) with knee osteoarthritis (130 patients with bilateral) and who had never
performed isokinetic testing underwent two bilateral knee extension-flexion
(concentric-concentric) isokinetic evaluations (5 repetitions) at 60 degrees
/sec. The tests were first performed on the dominant leg with 2 min of recovery
between test, and following a standardized warm-up that included 3 submaximal
isokinetic repetitions. The same procedure was repeated on the non-dominant leg.
The peak torque, peak torque adjusted for the body weight, total work,
coefficient of variation and agonist/antagonist ratio were compared between
tests. RESULTS:: Patients showed significant improvements in test 2 compared to
test 1, including higher levels of peak torque, peak torque adjusted for body
weight and total work, as well as lower coefficients of variation. The
agonist/antagonist relationship did not significantly change between tests. No
significant differences were found between the right and left legs for all
variables. CONCLUSION:: The results suggest that performing two tests with a
short recovery (2 min) between them could be used to reduce motor learning
effects on clinical isokinetic testing of the knee joint in knee osteoarthritis
patients.
PMID- 28492719
TI - Does aortic valve repair in valve-sparing aortic root reconstruction compromise
the longevity of the procedure?
AB - OBJECTIVES:: The effect of performing aortic valve repair in combination with
valve-sparing operation on the length of time for which patients are free from
reoperation is unclear. The objective of this study was to determine if the
performance of aortic valve repair during valve-sparing operation modified the
freedom from reoperation time. METHODS:: From January 2003 to July 2014, 78
patients with a mean age of 49+/-15 years underwent valve-sparing operation.
Sixty-eight percent of these patients were male. Twenty-two (28%) aortic valve
repair procedures were performed in this patient population. In the aortic valve
repair + valve-sparing operation group, 77.3% of patients had moderate/severe
aortic insufficiency, while in the valve-sparing operation group, 58.6% of
patients had moderate/severe aortic insufficiency (ns = not significant).
Additionally, 13.6% of patients in the aortic valve repair + valve-sparing
operation group had functional class III/IV, while 14.2% of patients in the valve
sparing operation group had functional class III/IV (ns). RESULTS:: The in
hospital and late mortality rates, for the aortic valve repair + valve-sparing
operation and valve-sparing operation groups were similar, as they were 4.5% and
3.6%; and 0% and 1.8%, respectively. In the aortic valve repair + valve-sparing
operation group, 0% of patients presented moderate/severe aortic insufficiency
during late follow-up, while in the valve-sparing operation group, 14.2% of
patients presented with moderate/severe aortic insufficiency during this period
(ns). In the aortic valve repair + valve-sparing operation group, 5.3% of
patients presented with functional class III/IV, while in the valve-sparing
operation group, 4.2% of patients presented with functional class III/IV (ns). In
the aortic valve repair + valve-sparing operation group, 0% of patients required
reoperation, while in the valve-sparing operation group, 3.6% of patients
required reoperation over a mean follow-up period of 1621+/-1156 days (75
patients). CONCLUSION:: Valve-sparing operation is a safe and long-lasting
procedure and performance of aortic valve repair when necessary does not increase
risk of reoperation on the aortic valve.
PMID- 28492720
TI - Association between language and hearing disorders - risk identification.
AB - OBJECTIVE:: To identify children at risk for hearing and/or language disorders
and to investigate the association between these risks by conducting pre
validated hearing and language screenings. METHODS:: The study was conducted
during a polio vaccination campaign in August of 2013 in basic health units in
western Sao Paulo. Parents of children between 2 and 5 years of age were asked to
complete two screening tools: a hearing questionnaire (regarding hearing
development) and a language production and comprehension scale (including the
major language development milestones). The screening tools were administered by
different researchers. We compared the risk of having language disorders among
children at risk for hearing loss versus children not at risk, as well as the
attributable risk and odds ratios. Chi-squared tests and logistic regression
analyses were used. RESULTS:: The study included 479 children with a mean age of
three and one-half years, of whom 26.9% were identified as at risk for deficits
in language production, 8.6% were at risk for deficits in language comprehension
and 14% were at risk for hearing disorders. The children at risk for hearing
disorders were twice as likely as those not at risk to exhibit language
production and comprehension deficits. CONCLUSION:: The results of this study
highlight the importance of establishing and adopting low-cost procedures such as
screenings to identify children at risk of developing language and/or hearing
disorders in early childhood.
PMID- 28492721
TI - Treatment of acromegaly patients at the Federal University of Triangulo Mineiro
(UFTM): Experience Report.
AB - OBJECTIVE:: To evaluate the effectiveness of the treatment of acromegaly patients
at the Federal University of Triangulo Mineiro. METHODS:: Cross-sectional and
retrospective study of thirty cases treated over a period of two decades.
RESULTS:: 17 men (56.7%) aged 14-67 years and 13 women aged 14-86 years were
analyzed. Twenty-one patients underwent transphenoidal surgery, whichwas
associated with somatostatin receptor ligands in 11 patients (39.3%),
somatostatin receptor ligands + radiotherapyin 5 patients (17.8%), radiotherapy
in 3 patients (10.7%), and radiotherapy + somatostatin receptorligands +
cabergoline in 1 patient (3.6%). Additionally, 2 patients underwent radiotherapy
and surgeryalone. Six patients received somatostatin receptor ligands before
surgery, and 2 were not treated due to refusal and death. Nine patients have
died, and 20 are being followed; 13 (65%) have growth hormonelevels o1 ng/mL, and
11 have normal insulin-like growth factor 1 levels. CONCLUSION:: The current
treatment options enable patients seen in regional reference centers to achieve
strict control parameters, which allows them to be treated close to their homes.
PMID- 28492722
TI - Insulin resistance and associated factors: a cross-sectional study of bank
employees.
AB - OBJECTIVE:: Insulin resistance is characterized by the failure of target cells to
respond to normal levels of circulating insulin, and this condition is related to
cardiovascular disease. This study sought to evaluate the prevalence of insulin
resistance and its association with markers of metabolic abnormalities and
metabolic syndrome in bank employees. METHODS:: A cross-sectional study was
performed on 498 working men and women aged >=20 years old. The Homeostasis Model
Assessment (HOMA-IR) was used to determine the presence of insulin resistance
based on cut-off values of <=2.71 for normal insulin levels and >2.71 for insulin
resistance, as established for the adult Brazilian population. RESULTS:: It was
observed that the 52 (10.4%) overweight individuals with insulin resistance were
4.97 times (95%CI 1.31-18.83) more likely to have high HOMA-IR values than the
normal-weight participants; among those who were obese, the likelihood increased
to 17.87 (95%CI 4.36-73.21). Individuals with large waist circumferences were
3.27 times (95%CI 1.03-10.38) more likely to develop insulin resistance than
those who were within normal parameters. The HOMA-IR values differed between
subjects with and without metabolic syndrome, with values of 2.83+/-2.5 and
1.10+/-0.81 (p=0.001), respectively. The levels of insulin, ultrasensitive C
reactive protein and uric acid were also associated with insulin resistance.
CONCLUSION:: The prevalence of insulin resistance among bank employees is high,
and insulin resistance is associated with and serves as a marker of metabolic
syndrome. Cardiovascular disease and metabolic syndrome-associated metabolic
abnormalities were observed, and insulin resistance may be a risk factor in this
group of professionals.
PMID- 28492723
TI - Hepatic Osteodystrophy: The Mechanism of Bone Loss in Hepatocellular Disease and
the Effects of Pamidronate Treatment.
AB - OBJECTIVES:: The present study was designed to evaluate the bone phenotypes and
mechanisms involved in bone disorders associated with hepatic osteodystrophy.
Hepatocellular disease was induced by carbon tetrachloride (CCl4). In addition,
the effects of disodium pamidronate on bone tissue were evaluated. METHODS:: The
study included 4 groups of 15 mice: a) C = mice subjected to vehicle injections;
b) C+P = mice subjected to vehicle and pamidronate injections; c) CCl4+V = mice
subjected to CCl4 and vehicle injections; and d) CCl4+P = mice subjected to CCl4
and pamidronate injections. CCl4 or vehicle was administered for 8 weeks, while
pamidronate or vehicle was injected at the end of the fourth week. Bone
histomorphometry and biomechanical analysis were performed in tibiae, while
femora were used for micro-computed tomography and gene expression. RESULTS::
CCl4 mice exhibited decreased bone volume/trabecular volume and trabecular
numbers, as well as increased trabecular separation, as determined by bone
histomorphometry and micro-computed tomography, but these changes were not
detected in the group treated with pamidronate. CCl4 mice showed increased
numbers of osteoclasts and resorption surface. High serum levels of receptor
activator of nuclear factor-kappaB ligand and the increased expression of
tartrate-resistant acid phosphatase in the bones of CCl4 mice supported the
enhancement of bone resorption in these mice. CONCLUSION:: Taken together, these
results suggest that bone resorption is the main mechanism of bone loss in
chronic hepatocellular disease in mice.
PMID- 28492724
TI - Human islet xenotransplantation in rodents: A literature review of experimental
model trends.
AB - Among the innovations for the treatment of type 1 diabetes, islet transplantation
is a less invasive method of treatment, although it is still in development. One
of the greatest barriers to this technique is the low number of pancreas donors
and the low number of pancreases that are available for transplantation. Rodent
models have been chosen in most studies of islet rejection and type 1 diabetes
prevention to evaluate the quality and function of isolated human islets and to
identify alternative solutions to the problem of islet scarcity. The purpose of
this study is to conduct a review of islet xenotransplantation experiments from
humans to rodents, to organize and analyze the parameters of these experiments,
to describe trends in experimental modeling and to assess the viability of this
procedure. In this study, we reviewed recently published research regarding islet
xenotransplantation from humans to rodents, and we summarized the findings and
organized the relevant data. The included studies were recent reports that
involved xenotransplantation using human islets in a rodent model. We excluded
the studies that related to isotransplantation, autotransplantation and
allotransplantation. A total of 34 studies that related to xenotransplantation
were selected for review based on their relevance and current data. Advances in
the use of different graft sites may overcome autoimmunity and rejection after
transplantation, which may solve the problem of the scarcity of islet donors in
patients with type 1 diabetes.
PMID- 28492726
TI - Theoretical basis, application, reliability, and sample size estimates of a
Meridian Energy Analysis Device for Traditional Chinese Medicine Research.
AB - OBJECTIVES:: The Meridian Energy Analysis Device is currently a popular tool in
the scientific research of meridian electrophysiology. In this field, it is
generally believed that measuring the electrical conductivity of meridians
provides information about the balance of bioenergy or Qi-blood in the body.
METHODS AND RESULTS:: PubMed database based on some original articles from 1956
to 2014 and the authors clinical experience. In this short communication, we
provide clinical examples of Meridian Energy Analysis Device application,
especially in the field of traditional Chinese medicine, discuss the reliability
of the measurements, and put the values obtained into context by considering
items of considerable variability and by estimating sample size. CONCLUSION:: The
Meridian Energy Analysis Device is making a valuable contribution to the
diagnosis of Qi-blood dysfunction. It can be assessed from short-term and long
term meridian bioenergy recordings. It is one of the few methods that allow
outpatient traditional Chinese medicine diagnosis, monitoring the progress,
therapeutic effect and evaluation of patient prognosis. The holistic approaches
underlying the practice of traditional Chinese medicine and new trends in modern
medicine toward the use of objective instruments require in-depth knowledge of
the mechanisms of meridian energy, and the Meridian Energy Analysis Device can
feasibly be used for understanding and interpreting traditional Chinese medicine
theory, especially in view of its expansion in Western countries.
PMID- 28492725
TI - Breast cancer screening in developing countries.
AB - Developing countries have limited healthcare resources and use different
strategies to diagnose breast cancer. Most of the population depends on the
public healthcare system, which affects the diagnosis of the tumor. Thus, the
indicators observed in developed countries cannot be directly compared with those
observed in developing countries because the healthcare infrastructures in
developing countries are deficient. The aim of this study was to evaluate breast
cancer screening strategies and indicators in developing countries. A systematic
review and the Population, Intervention, Comparison, Outcomes, Timing, and
Setting methodology were performed to identify possible indicators of
presentation at diagnosis and the methodologies used in developing countries. We
searched PubMed for the terms "Breast Cancer" or "Breast Cancer Screening" and
"Developing Country" or "Developing Countries". In all, 1,149 articles were
identified. Of these articles, 45 full articles were selected, which allowed us
to identify indicators related to epidemiology, diagnostic intervention
(diagnostic strategy, diagnostic infrastructure, percentage of women undergoing
mammography), quality of intervention (presentation of symptoms at diagnosis,
time to diagnosis, early stage disease), comparisons (trend curves,
subpopulations at risk) and survival among different countries. The
identification of these indicators will improve the reporting of methodologies
used in developing countries and will allow us to evaluate improvements in public
health related to breast cancer.
PMID- 28492727
TI - Active caspase-3 expression levels as bioindicator of individual
radiosensitivity.
AB - Several molecules and events involved in cell response to radiation-induced
damage have been investigated towards a personalized radiotherapy. Considering
the importance of active caspase-3 in the proteolytic cascade that ensures
radiation-induced apoptosis execution, this research was designed to evaluate the
expression levels of this protein as a bioindicator of individual
radiosensitivity. Peripheral blood samples of 10 healthy individuals were gamma
irradiated (cobalt-60 source) with 1, 2 and 4 Gy (control: non-irradiated
samples), and active caspase-3 expression levels were measured in lymphocytes, by
flow cytometry, ex vivo and after different times of in vitro incubation (24, 48
and 72 hours). Short-term incubation of 24 h was the most adequate condition to
evidence correlations between dose radiation and active caspase-3 expression. For
each radiation dose, it was observed a significant inter-individual variation in
active caspase-3 expression intensity, suggesting that this parameter may be
suitable for evidence individual radiosensitivity. The methodology presented and
discussed in this work may help to predict healthy tissues response to radiation
exposure toward the better patient outcome.
PMID- 28492728
TI - Evaluation of the predisposition and clinical impact of BK virus replication in
kidney transplant patients.
AB - The BK virus (BKV) produces a subclinical kidney infection in immunocompetent
individuals. However, viremia may occur in kidney transplant patients with
ongoing immunosuppression. BKV-associated nephropathy (BKVN) has no specific
treatment and is a leading cause of organ transplant loss. In this study, we
evaluated the predisposition and the clinical impact of BKV replication in kidney
transplant patients during post-transplant monitoring in a reference institution
in Brazil. Demographic, clinical and laboratory data generated during routine
outpatient follow-up were retrospectively collected. BK viremia was investigated
using real-time polymerase chain reaction. Of the 553 participants, 7.4% (n = 41)
presented BKV replication. Of these, 16 (39%) lost their kidney graft and
interstitial nephritis was identified on kidney biopsy in 50% of the cases. Among
the evaluated variables, only the use of the immunosuppressant mycophenolate
sodium was identified as a risk factor for viremia (OR 7.96; 95% CI 2.35 to
26.98). The graft survival estimate in BKV-positive patients was significantly
reduced (24.8% vs. 85.6%) after 10 years of transplantation. We concluded that
defining predisposing factors remains an important challenge for the prevention
and control of BKV activity following kidney transplantation, especially
considering the development of BKVN and its strong effect on graft maintenance.
PMID- 28492729
TI - CYP2B6 516 G>T polymorphism and side effects of the central nervous system in HIV
positive individuals under Efavirenz treatment: Study of a sample from southern
Brazil.
AB - This study aimed to identify the 516 G>T polymorphism of the CYP2B6 gene and
evaluate its influence on central nervous system (CNS) side effect development in
HIV-positive individuals undergoing Efavirenz (EFV) treatment in a population
from southern Brazil. Additionally, we performed a survey on the clinical and
epidemiological characteristics of our sample. In addition to medical records
evaluation, whole blood of 89 individuals was analyzed for viral load, T
lymphocyte count (CD4+ and CD8+), and the polymorphism. Considering the side
effects of the CNS reported by individuals but without considering the genetic
variables, no statistically significant association was noted between the adverse
effects and the antiretroviral treatment (including or not EFV). In addition, no
statistically significant difference was noted for the influence of genotype on
the viral load or the number of T lymphocytes (CD4+ and CD8+) among individuals
undergoing EFV treatment. This is the first study that investigated the impact of
the 516 G>T polymorphism of the CYP2B6 gene among HIV-positive individuals from
southern Brazil. Its clinical significance indicates the need for prospective
studies in this population.
PMID- 28492730
TI - Paleoenvironmental Evolution of Continental Carbonates in West-Central Brazil.
AB - This paper presents a sedimentological and stratigraphical study of Quaternary
(Middle to Late Pleistocene/Holocene) continental carbonates outcrops inside
Pantanal Basin and its surroundings, especially in Serra da Bodoquena, Pantanal
do Miranda and Corumba/Ladario plateau, in the state of Mato Grosso do Sul, as
well as in Serra das Araras, in the state of Mato Grosso. The aim is to
understand the depositional paleoenvironments and analyse climate and tectonic
influences in their genesis and evolution. The results show that the deposition
of these continental carbonates started in the Middle to Late Pleistocene and
have continued, with some interruptions, until the present days. Sedimentary
successions were identified in the different areas, without complete correlation.
Two sedimentary successions separated by an erosional surface were described in
Serra da Bodoquena and Serra das Araras. In Corumba and Pantanal do Miranda, only
one succession was described. These successions were deposited in elongated lakes
parallel to fault planes; small lakes, related plains and plateaus; springs
related to cliffs produced by faulting; rivers conditioned by topographic
variation. The climatic interpretation, without proper temporal resolution,
obtained by the stable-isotope composition and stratigraphic interpretation,
indicates alternation of dry and wet periods. The Neoproterozoic faults with
their neotectonics and the subsidence of the Pantanal Basin, are the major
control for carbonated water flow and development of depositional areas,
gradually turning plateaus into slight tilted areas, allowing the evolution of
depositional systems from lakes to rivers.
PMID- 28492731
TI - Brazilian Scientific Mobility Program - Science without Borders - Preliminary
Results and Perspectives.
AB - The Brazilian Scientific Mobility Program - Science without Borders (SwB) - saw
the concession of over 101 thousand scholarships for Brazilian STEM students and
education professionals to attend universities worldwide. As the first phase of
this program ends, it is time to take a first look at its impacts, mainly on the
undergraduate student body (79% of total scholarships implemented). Benefits
included a 6-month language course (optional), a one year undergraduate course
and optional 2 month internship in a university, government laboratory or
technology company. Positive impacts have been seen on entrance into post
graduate programs (>20% of SwB students compared to <5% of the overall student
body of similar fields), as well as high representation of lower income families
(>50% from families with less than 6 minimum wages per month). The impact of the
program will need to be evaluated over the next years, but innovation on the part
of the students is already apparent. Any new SwB program needs to take into
account the lessons learned from this first experience and therefore
recommendations are presented.
PMID- 28492732
TI - Going Beyond Academic Integrity Might Broaden our Understanding of Plagiarism in
Science Education: A Perspective from a Study in Brazil.
AB - Fostering innovation and creativity is a priority in the science and education
policy agenda of most countries, which have advocated that innovative minds and
processes will boost scientific and economic growth. While our knowledge society
has embraced this view, fostering creativity is among the major challenges faced
by educators and policymakers. For example, plagiarism, which may be considered a
form of imitation and repetition, is a global concern at schools and
universities. However, most discussions focus on academic integrity, which, we
believe, leaves some gaps in the approach to the problem. As part of an ongoing
project on plagiarism, science and education policy, we show results from a
survey sent to 143 high-school science teachers at one of the most highly
regarded federal schools in Brazil. Among respondents (n=42), about 50% admit
that students plagiarize in assignments. Additionally, many of these educators
suggest that the way biology, chemistry and physics are taught at school
stimulates more repetition than creativity. Our findings are consistent with the
need for a broader perspective on plagiarism and with initiatives to stimulate
creativity and critical thinking among students. Although we offer a perspective
from Brazil, it may illuminate current discussions on plagiarism, particularly in
emerging countries.
PMID- 28492733
TI - Simultaneous Determination of Furan and Vinyl Acetate in Vapor Phase of
Mainstream Cigarette Smoke by GC-MS.
AB - A simple and sensitive method for simultaneous determination of furan and vinyl
acetate (VA) in vapor phase of mainstream cigarette smoke with cold trap and gas
chromatography-mass spectrometry (GC-MS) was developed. A Cambridge filter pad
(CFP) was placed in front of the impingers of smoking machine to remove the
particle phase from cigarette smoke. Furan and VA in vapor phase of mainstream
cigarette smoke were collected in two impingers connected in series by filled
with methanol at -78 degrees C. The solutions were added with deuterium-labeled
furan-d4 and VA-d6 as internal standards and analyzed by GC-MS. The results
showed that the calibration curves for furan and VA were linear (r2 > 0.9995)
over the studied concentration range. The intra- and inter-day precision values
for furan and VA were <7.07% and <9.62%, respectively. The extraction recoveries
of furan and VA were in the range of 94.5-97.7% and 92.3-94.9%, respectively.
Moreover, the limits of detection for furan and VA were 0.028 ug mL-1 and 1.3 ng
mL-1, respectively. The validated method has been successfully applied to
determine the emissions of furan and VA in the vapor phase of mainstream
cigarette smoke under International Organization for Standardization (ISO) and
Canadian Intense (CI) smoking regimen.
PMID- 28492734
TI - Anesthesia of Epinephelus marginatus with essential oil of Aloysia polystachya:
an approach on blood parameters.
AB - This study investigated the anesthetic potential of the essential oil (EO) of
Aloysia polystachya in juveniles of dusky grouper (Epinephelus marginatus). Fish
were exposed to different concentrations of EO of A. polystachya to evaluate time
of induction and recovery from anesthesia. In the second experiment, fish were
divided into four groups: control, ethanol and 50 or 300 uL L-1 EO of A.
polystachya, and each group was submitted to induction for 3.5 min and recovery
for 5 or 10 min. The blood gases and glucose levels showed alterations as a
function of the recovery times, but Na+ and K+ levels did not show any
alteration. In conclusion, the EO from leaves of A. polystachya is an effective
anesthetic for dusky grouper, because anesthesia was reached within the
recommended time at EO concentrations of 300 and 400 uL L-1. However, most
evaluated blood parameters showed compensatory responses due to EO exposure.
PMID- 28492735
TI - Subclinical Diabetes.
AB - Type 2 diabetes mellitus (T2DM) is increasing in prevalence worldwide, and those
non-diagnosed or misdiagnosed comprise a significant group compared to those
diagnosed. Accumulated scientific evidence indicate that the current diagnostic
markers (fasting glycemia, 2h glycemia after an oral glucose load and HbA1c) are
indeed late diagnostic criteria when considering the incidence of diabetes
related complications and comorbidities, which are also at high risk in some
groups among normoglycemic individuals. Additionally, the earlier identification
of future risk of diabetes is desirable since it would allow better adherence to
preventive actions such as lifestyle intervention, ultimately avoiding
complications and minimizing the economic impact/burden on health care expenses.
Insulin resistance and hyperhormonemia (insulin, amylin, glucagon) are non
disputable hallmarks of T2DM, which already takes place among these
normoglycemic, otherwise health subjects, characterizing a state of subclinical
diabetes. Insulin resistance and hyperinsulinemia can be computed from fasting
plasma insulin as an independent variable in normoglycemia. An overview of the
current diagnostic criteria, disease onset, complications, comorbidities and
perspectives on lifestyle interventions are presented. A proposal for early
detection of subclinical diabetes from routine evaluation of fasting plasma
insulin, which is affordable and robust and thus applicable for the general
population, is further suggested.
PMID- 28492736
TI - Effect of drying method on mechanical, thermal and water absorption properties of
enzymatically crosslinked gelatin hydrogels.
AB - Enzymatically crossliked gelatin hydrogel was submitted to two different drying
methods: air drying and freeze drying. The resulting polymeric tridimensional
arrangement (compact or porous, respectively) led to different thermal and
swelling properties. Significant differences (p < 0.05) on thermal and mechanical
characteristics as well as swelling in non-enzymatic gastric and intestinal
simulated fluids (37 oC) were detected. Water absorption data in such media was
modelled according to Higuchi, Korsmeyer-Peppas, and Peppas-Sahlin equations.
Freeze dried hydrogel showed Fickian diffusion behavior while air dried hydrogels
presented poor adjustment to Higuchi model suggesting the importance of the
relaxation mechanism at the beginning of swelling process. It was possible to
conclude that the same gelatin hydrogel may be suitable to different applications
depending on the drying process used.
PMID- 28492737
TI - The use of medicinal plants and the role of faith in family care.
AB - Objective: To understand the use of medicinal plants and the role of faith in the
family care system. Method: The adopted methodology is qualitative research,
conducted in April and July 2015, in a municipality of Rio Grande do Sul, Brazil,
Brazil, with three informants who have knowledge of the healthcare practices. The
data were interpreted using interpretive anthropology. Results: Data
interpretation led to two categories: Medicinal plants in health care and Care
with the use of plants in the blessing ritual. It was identified that the use of
plants and faith healing is a particular form of self-care in that given
community. The purpose of this practice is to cure people from a biological and
comprehensive perspective, involving the body, soul, spirit, and environment.
Conclusion: The research revealed that medicinal plants go beyond the merely
biological relationship in the family care system. Use of these plants is not
based on the principle of buying and selling, but rather on the act of
exchanging, giving, receiving, and reciprocating.
PMID- 28492739
TI - Relationship between Resting Heart Rate, Blood Pressure and Pulse Pressure in
Adolescents.
AB - Background:: High resting heart rate is considered an important factor for
increasing mortality chance in adults. However, it remains unclear whether the
observed associations would remain after adjustment for confounders in
adolescents. Objectives:: To analyze the relationship between resting heart rate,
blood pressure and pulse pressure in adolescents of both sexes. Methods:: A cross
sectional study with 1231 adolescents (716 girls and 515 boys) aged 14-17 years.
Heart rate, blood pressure and pulse pressure were evaluated using an
oscillometric blood pressure device, validated for this population. Weight and
height were measured with an electronic scale and a stadiometer, respectively,
and waist circumference with a non-elastic tape. Multivariate analysis using
linear regression investigated the relationship between resting heart rate and
blood pressure and pulse pressure in boys and girls, controlling for general and
abdominal obesity. Results:: Higher resting heart rate values were observed in
girls (80.1 +/- 11.0 beats/min) compared to boys (75.9 +/- 12.7 beats/min) (p <=
0.001). Resting heart rate was associated with systolic blood pressure in boys
(Beta = 0.15 [0.04; 0.26]) and girls (Beta = 0.24 [0.16; 0.33]), with diastolic
blood pressure in boys (Beta = 0.50 [0.37; 0.64]) and girls (Beta = 0.41 [0.30;
0.53]), and with pulse pressure in boys (Beta = -0.16 [-0.27; -0.04]).
Conclusions:: This study demonstrated a relationship between elevated resting
heart rate and increased systolic and diastolic blood pressure in both sexes and
pulse pressure in boys even after controlling for potential confounders, such as
general and abdominal obesity. Fundamento:: A frequencia cardiaca de repouso e
considerada um importante fator de aumento de mortalidade em adultos. Entretanto,
ainda e incerto se as associacoes observadas permanecem apos ajuste para fatores
de confusao em adolescentes. Objetivos:: Analisar a relacao entre frequencia
cardiaca de repouso, pressao arterial e pressao de pulso em adolescentes dos dois
sexos. Metodos:: Estudo transversal com 1231 adolescentes (716 meninas e 515
meninos, idade de 14-17 anos). Frequencia cardiaca, pressao arterial e pressao de
pulso foram avaliadas com esfigmomanometro oscilometrico validado para essa
populacao. Peso e altura foram medidos com balanca eletronica e estadiometro,
respectivamente, e a circunferencia abdominal, com uma fita inextensivel. Analise
multivariada com regressao linear investigou a relacao entre frequencia cardiaca
de repouso, pressao arterial e pressao de pulso em meninos e meninas, controlando
para obesidade geral e abdominal. Resultados:: Valores maiores de frequencia
cardiaca de repouso foram observados em meninas (80,1 +/- 11,0 bpm) em comparacao
a meninos (75,9 +/- 12,7 bpm) (p <= 0,001). Frequencia cardiaca de repouso
associou-se com pressao arterial sistolica em meninos [Beta = 0,15 (0,04; 0,26)]
e meninas [Beta = 0,24 (0,16; 0,33)], com pressao arterial diastolica em meninos
[Beta = 0,50 (0,37; 0,64)] e meninas [Beta = 0,41 (0,30; 0,53)], e com pressao de
pulso apenas em meninos [Beta = -0,16 (-0,27; -0,04)]. Conclusoes:: Este estudo
demonstrou a relacao da frequencia cardiaca de repouso elevada com aumento das
pressoes arteriais sistolica e diastolica em ambos os sexos e com pressao de
pulso em meninos, mesmo apos controle para potenciais fatores de confusao, como
obesidade geral e abdominal.
PMID- 28492738
TI - Factors Associated With Coronary Artery Disease Progression Assessed By Serial
Coronary Computed Tomography Angiography.
AB - Background: Coronary computed tomography angiography (CCTA) allows for
noninvasive coronary artery disease (CAD) phenotyping. Factors related to CAD
progression are epidemiologically valuable. Objective: To identify factors
associated with CAD progression in patients undergoing sequential CCTA testing.
Methods: We retrospectively analyzed 384 consecutive patients who had at least
two CCTA studies between December 2005 and March 2013. Due to limitations in the
quantification of CAD progression, we excluded patients who had undergone
surgical revascularization previously or percutaneous coronary intervention (PCI)
between studies. CAD progression was defined as any increase in the adapted
segment stenosis score (calculated using the number of diseased segments and
stenosis severity) in all coronary segments without stent (in-stent restenosis
was excluded from the analysis). Stepwise logistic regression was used to assess
variables associated with CAD progression. Results: From a final population of
234 patients, a total of 117 (50%) had CAD progression. In a model accounting for
major CAD risk factors and other baseline characteristics, only age (odds ratio
[OR] 1.04, 95% confidence interval [95%CI] 1.01-1.07), interstudy interval (OR
1.03, 95%CI 1.01-1.04), and past PCI (OR 3.66, 95%CI 1.77-7.55) showed an
independent relationship with CAD progression. Conclusions: A history of PCI with
stent placement was independently associated with a 3.7-fold increase in the odds
of CAD progression, excluding in-stent restenosis. Age and interstudy interval
were also independent predictors of progression.
PMID- 28492740
TI - Selective COX-2 Inhibitor (Meloxicam) and Tooth-Supporting Bone Quality. A
Histomorphometric Study in Rats.
AB - The effects of the non-steroidal anti-inflammatory drugs (NSAIDs) on bone
quantity and quality were investigated for years. However, there is lack of
information on the impact of NSAIDs on the quality of tooth-supporting alveolar
bone in absence of periodontal inflammation. Thus, the aim of this study was to
evaluate histometrically the influence of a selective COX-2 NSAID (Meloxicam) on
the inter-radicular bone mineral density in rats. Forty-nine adult male Wistar
rats were randomly divided into four experimental groups: Subcutaneous injection
of 0.9% sterile saline for 15 days (G1; n=12) and 45 days (G2; n=11); and
subcutaneous injection of Meloxicam for 15 days (G3; n=13) and 45 days (G4;
n=13). Mineral density was histometrically determined in the inter-radicular area
of the 1st mandibular molars and data analysis performed by two-way ANOVA (a=5%).
Results showed no interaction between time and treatment (p>0.05) and that
meloxicam did not affect the alveolar bone density. In contrast, it was found
that inter-radicular alveolar bone density increased with time (91.88+/-3.08% and
92.86+/-2.38% for groups 15 and 45 days, respectively) (p<0.05). Within the
limits of this study, daily administration of a selective COX-2 inhibitor
(Meloxicam) did not affect the quality of the inter-radicular alveolar bone in
absence of periodontal infection.
PMID- 28492741
TI - Effect of Alox-15 Polymorphism on GCF Levels of Lipoxin-A4 in Chronic
Periodontitis: A Preliminary Study.
AB - Lipoxins play an important role in periodontal resolution, hence, investigation
of genetic polymorphism of lipoxin gene may provide important information on the
role of lipoxins in periodontal disease pathogenesis. The aim of this study was
to investigate a polymorphism of C-to-T substitution at position c.-292 in ALOX15
(reticulocyte-type 15 lipoxygenase 1) gene in patients with chronic periodontitis
and to associate the polymorphism with gingival crevicular fluid (GCF) lipoxin A4
(LXA4) levels. Forty-five chronic periodontitis and 45 periodontally healthy
patients were included in this case-control study. Plaque index, calculus index,
sulcus bleeding index, full mouth probing depth (PD) and clinical attachment loss
(CAL) were recorded. GCF and blood samples were collected. GCF was analyzed for
LXA4 levels by enzyme linked immunosorbant assay. Genotyping of ALOX15
polymorphism was studied using PCR. Mean LXA4 was lower in periodontitis group
compared to the periodontally healthy group. There was a negative correlation
between CAL and LXA4. The CC genotype was higher in the study group than in the
control group. In the study group, mean CAL was significantly lower among
individuals with the CT genotype. Mean LXA4 was significantly lower in CC
genotype (45.0+/-7.11 ng/mL) compared to CT genotype (50.81+/-5.81 ng/mL) among
the patients with periodontitis. The results suggest that LXA4 and c.-292T allele
are associated with periodontal health. Polymorphisms in the ALOX15 gene may
influence periodontal disease pathogenesis. Hence, investigation of such
polymorphisms could benefit the evaluation of lipoxins role in periodontal
disease.
PMID- 28492742
TI - DNA Aneuploidy in Malignant Salivary Gland Neoplasms is Independent of USP44
Protein Expression.
AB - Chromosomal instability, leading to aneuploidy, is one of the hallmarks of human
cancers. USP44 (ubiquitin specific peptidase 44) is an important molecule that
plays a regulatory role in the mitotic checkpoint and USP44 loss causes
chromosome mis-segregation, aneuploidy and tumorigenesis in vivo. In this study,
it was investigated the immunoexpression of USP44 in 28 malignant salivary gland
neoplasms and associated the results with DNA ploidy status assessed by image
cytometry. USP44 protein was widely expressed in most of the tumor samples and no
clear association could be established between its expression and DNA ploidy
status or tumor size. On this basis, it may be concluded that the aneuploidy of
the salivary gland cancers included in this study was not driven by loss of USP44
protein expression.
PMID- 28492743
TI - Presence of Cells in Fresh-Frozen Allogeneic Bone Grafts from Different Tissue
Banks.
AB - Bone replacement materials have been widely used to reconstruct atrophic
jawbones. Based on previous reports demonstrating the presence of viable cells in
bone blocks even after processing by musculoskeletal tissue banks for orthopedic
use, the aim of this study was to evaluate the presence of cells in bone blocks
from three Brazilian tissue banks for maxillary reconstructions. All samples were
processed by the respective tissue banks, according to the guidelines of the
Brazilian National Sanitary Surveillance Agency. Three samples were removed from
each block for subsequent histological processing and stained using hematoxylin &
eosin. Further evaluation included section staining by the Feulgen method and
ultrastructural analysis using scanning electron microscopy (SEM). Light
microscopy images from all bone samples showed presence of osteocyte-like cells
in all groups and intense Feulgen staining, demonstrating presence of DNA in bone
even after tissue processing. The ultrastructural analysis showed red blood cells
in lacunae within the bone tissue. In conclusion, despite bone tissue processing
by the musculoskeletal tissue banks, cells may be found within the bone used for
allogeneic grafts.
PMID- 28492744
TI - Surface Properties of Temporary Soft Liners Modified by Minimum Inhibitory
Concentrations of Antifungals.
AB - Evaluating the addition of minimum inhibitory concentrations (MICs) of
antifungals for Candida albicans biofilm on the hardness and roughness of
temporary denture soft liners. Specimens (n=8; 36*7*6 mm) of tissue conditioner
(Softone) and resilient liner (Trusoft) were produced either without (control) or
with incorporation of drugs at MICs: nystatin (0.032 g/mL), chlorhexidine
diacetate (0.064 g/mL), ketoconazole (0.128 g/mL), miconazole (0.256 g/mL) and
itraconazole (0.256 g/mL). Specimens were stored in distilled water at 37
degrees C for 24 h, 7 days and 14 days prior to the hardness/roughness
measurements. Data were analyzed by 3-way ANOVA and Tukey HSD test (alpha=0.05).
The addition of the antifungals into both materials demonstrated no evident
hardness change or decrease of this property compared with the control, except
for miconazole in Softone, which increased the hardness after 14 days (p=0.003).
The addition of nystatin into both materials, chlorhexidine in Trusoft and
ketoconazole in Softone resulted in no significant changes of roughness compared
with the control, after 7 days and 14 days (p>0.05). In these periods,
itraconazole increased the roughness of both materials (p<0.001). The addition of
all antifungals, except for the miconazole in Softone, resulted in no deleterious
effects on the materials' hardness over the evaluation time. The MICs of nystatin
in both temporary soft lining materials, ketoconazole in Softone and
chlorhexidine in Trusoft resulted in no deleterious effects for roughness up to
14 days.
PMID- 28492745
TI - Cytotoxicity Evaluation of Root Canal Sealers Using an In Vitro Experimental
Model with Roots.
AB - The aim of the present study was to evaluate the cytotoxicity of root canal
sealers under conditions closely resembling a clinical reality. A primary human
fibroblast cell line was seeded in 24-well acrylic plates with Dulbecco's
modified Eagle's medium supplemented with 10% serum fetal bovine (SFB) and
incubated for 24 h. Root canals from premolars were filled and individually
attached to nylon devices to be stabilized in the wells with the already seeded
cells. Specimens were divided into groups as follows: Control: gutta-percha cones
(GPC); AH Plus+GPC; Sealapex+GPC; MTA Fillapex+GPC and Endofill+GPC. After 24 and
48 h, cell viability and morphology were evaluated by MTT assay and scanning
electron microscopy (SEM), respectively. Statistical analysis was performed by
Mann-Whitney test, complemented by Kruskal Wallis test (p<0.05). Only Endofill
presented cytotoxicity after 24 h. MTA Fillapex and Endofill reduced the
production of succinic desidrogenase after 48 h. AH Plus was non-toxic at any
time point. SEM showed that the AH Plus and MTA Fillapex groups presented
fibroblasts with morphology close to the control group, while the Endofill group
presented few cells with thin extensions cells. The present study showed that
good results were present in AH Plus and Sealapex, but not the Endofill group
after 48 h. The method used enabled evaluation of the cytotoxicity of the studied
sealers that diffused through the root apex.
PMID- 28492746
TI - ?
AB - Developing new restorative materials should avoid damage to tissue structures.
This study evaluated the biocompatibility of a commercial dental glass ionomer
cement (GIC) mechanically reinforced with cellulose microfibers (GIC+CM) or
cellulose nanocrystals (GIC+CN) by implantation of three test specimens in
subcutaneous tissue in the dorsal region of 15 Rattus norvegicus albinus rats.
Each rat received one specimen of each cement, resulting in the following groups
(n=15): Group GIC (Control), Group GIC+CM and Group GIC+NC. After time intervals
of 7, 30 and 60 days, the animals were sacrificed and the following aspects were
histologically evaluated: type of inflammatory cells, fibroblasts, blood vessels,
macrophages, giant cells, type of inflammatory reaction and capsule thickness
(um). These events were scored as (-) absent, (+) light, (++) moderate and (+++)
intense. The results were statistically analyzed by Kruskal-Wallis test and Mann
Whitney post test. At 7 days, Group GIC+NC showed more favorable tissue repair
because quantitatively there were more fibroblasts (p=0.022), fewer macrophages
(p=0.008) and mononuclear cells (p=0.033). Polymorphonuclear neutrophils and
giant cells were absent in all experimental periods. At 60 days, test specimens
in Group GIC+NC were surrounded by a fibrous tissue capsule with reduced
thickness (26.72+/-2.87 um) in comparison with Group GIC+CM (41.21+/-3.98 um)
(p=0.025). In general, all biomaterials showed satisfactory biocompatibility, but
glass ionomer cement modified with cellulose nanocrystals showed a more advanced
tissue repair.
PMID- 28492747
TI - Common Operative Procedural Errors and Clinical Factors Associated with Root
Canal Treatment.
AB - Operative procedural errors must be well analyzed in order to avoid influence
negatively the root canal treatment (RCT) prognosis. The successful RCT prevents
tooth loss and avoids pain and apical periodontitis. This review aimed to
categorize common operative procedure errors and clinical factors associated with
RCT. Based on this, will be approached common errors of procedures within the
clinical operative sequence: endodontic treatment planning, pulp and periapical
disease diagnosis, anaesthesia, access cavity preparation, isolation with rubber
dam, root canal preparation, root canal filling and retreatment, restoration of
endodontically treated teeth, postoperative pain, follow up of endodontically
treated teeth. The professional must remind that in each phase of RCT an
operative error may have adverse implication on prognosis, and these errors
characterize risk factors to failure. The knowledge of probable operative
procedural errors and its consequences are essentials to avoid future problems to
the tooth health.
PMID- 28492748
TI - Influence of Resin Cements on Color Stability of Different Ceramic Systems.
AB - The purpose of this study was to evaluate color stability of two dental ceramics
cemented with two resin cements, assessing the color difference (DeltaE00) by the
measurement of L*, a*, b*, c* and h* of transmittance. The combination of two
ceramic system (feldspathic and lithium disilicate) and two resin cements - color
A3 (RelyX ARC and Variolink II) resulted in 4 groups (n=5). Ten disks-shaped
specimens were fabricated for each ceramic system (10x1.5 mm), etched with
hydrofluoric acid (10%) and silanized prior to cementation. The color analysis
was performed 24 h after cementation of the samples and after 6 months of storage
in relative humidity by means of spectrophotometry. The DeltaE00 values were
analyzed statistically by two-way ANOVA followed by the Tukey test (p<0.05). One
way ANOVA were calculated for the means of individual color coordinates (L*, a*,
b*, c* and h*). Two-way ANOVA showed that only the ceramic factor was significant
(p=0.003), but there was no difference for the cement factor (p=0.275) nor for
the ceramic/cement interaction (p=0.161). The feldspathic ceramic showed the
highest values of DeltaE00. Variations in L*, a*, b*, c* and h* were more
significant for feldspathic ceramic. In conclusion, storage alters similarly the
optical properties of the resin cements and feldspathic porcelain was more
susceptible to cement color change after aging.
PMID- 28492749
TI - Triazine Compound as Copolymerized Antibacterial Agent in Adhesive Resins.
AB - The aim of this study was to formulate and evaluate an experimental adhesive
resin with the addition of 1,3,5-triacryloylhexahydro-1,3,5-triazine at different
concentrations. Experimental adhesive resins were obtained by mixing 50% wt
bisphenol A glycol dimethacrylate (BisGMA), 25% wt triethylene glycol
dimethacrylate (TEGDMA), 25% wt 2-hydroxyethyl methacrylate (HEMA) and
photoinitiator system. The triazine compound was added in 1, 2.5 and 5% wt to a
base adhesive resin and one group remained with no triazine as control group. The
experimental adhesive resins were analyzed for antibacterial activity (n=3),
degree of conversion (n=3) and softening in solvent (n=3). Data distribution was
evaluated by Kolmogorov-Smirnov test, paired t test, one-way ANOVA and Tukey's
with a 0.05 level of significance. All groups with added triazine compound showed
antibacterial activity against Streptococcus mutans (p<0.05). All groups achieved
more than 70% degree of conversion, but there was no difference in this chemical
property (p>0.05). The initial Knoop hardness was higher in 2.5 and 5% wt groups
(p<0.05) and both groups present lower percentage variation of Knoop hardness
after solvent degradation. The present study formulated an antibacterial adhesive
resin with a non-releasing agent able to copolymerize with the comonomeric blend,
improving the restorative material's properties.
PMID- 28492750
TI - Relationship between Initial Attendance after Dental Trauma and Development of
External Inflammatory Root Resorption.
AB - This clinical study aimed to evaluate the relationship of the delay between
dental trauma and the initial attendance to the development of external
inflammatory root resorption in permanent teeth affected by severe luxation.
Sixty-seven patients, aged between 11 and 56 years, presenting 133 injured teeth
with closed apex (56 extrusive luxation, 69 lateral luxation and 8 intrusive
luxation) were followed up for a minimum of 24 months. The time elapsed between
dental trauma and the initial attendance was recorded. The presence of necrotic
pulp and external inflammatory resorption for each type of trauma was verified.
Fisher's exact test was used to verify the influence of the initial attendance
date at the Dental Trauma Center and the development of inflammatory resorption
(p<0.05). The odds ratio was used to check the risk of developing external
inflammatory resorption due to delay in seeking treatment. Pulp necrosis was
observed in 105 teeth (78.9%) and external inflammatory resorption was detected
in 17.8% cases of extrusive luxation (10 teeth), 15.9% of lateral luxation (11
teeth) and 25% of intrusive luxation (2 teeth). For lateral luxation, extended
delay between the date of injury and initial attendance influenced the occurrence
of external inflammatory resorption (p=0.0174). Patients who began treatment 45
days after the injury were 3.4 times more likely to develop external inflammatory
resorption than patients who sought treatment after the trauma. Treatment late
after the occurrence of dental trauma can impair the prognosis and result in the
development of external inflammatory resorption in luxated teeth.
PMID- 28492751
TI - Influence of Thermal Cycles Number on Bond Strength of Metallic Brackets to
Ceramic.
AB - The aim of this study was to evaluate the effect of different number of thermal
cycles on the shear bond strength (SBS) of metallic orthodontic brackets bonded
to feldspathic ceramic by a composite resin. Twenty-five ceramic cylinders were
etched with 10% hydrofluoric acid for 60 s and received two layers of silane.
Brackets were bonded to the cylinders using Transbond XT and assigned to 5 groups
(n=5): Group 1 - Control group (without thermal cycling); Group 2 - 500 thermal
cycles; Group 3 - 5,000 thermal cycles; Group 4 - 7,000 thermal cycles and Group
5 - 10,000 thermal cycles. Light-activation was carried out by Radii Plus LED.
SBS testing was carried out after 24 h of storage in deionized water and thermal
cycling (5/55 oC and 30 s dwell time). Five brackets were bonded to each
cylinder, totalizing 25 brackets for each group. Data were submitted to one-way
ANOVA and Tukey's test (alpha=0.05). The Adhesive Remnant Index (ARI) was
evaluated at 8* magnification. The SBS (MPa) of control group (9.3+/-0.8), 500
(9.0+/-0.7) and 5,000 (8.4+/-0.9) thermal cycles were significantly higher than
those after 7,000 (6.8+/-0.6) and 10,000 (4.9+/-1.0) thermal cycles (p<0.05). The
ARI showed a predominance of Scores 0 (adhesive failure) prevailed in all groups,
as shown by the ARI, with increased scores 1 and 2 (mixed failures) for control
group and 500 thermal cycles. In conclusion, thermal fatigue may compromise the
bonding integration between metallic brackets and ceramic restorations. For in
vitro testing, use of at least 7,000 cycles is advised to result in significant
fatigue on the bonding interface.
PMID- 28492752
TI - Effect of Metal Primers on Bond Strength of a Composite Resin to Nickel-Chrome
Metal Alloy.
AB - This study evaluated the effects of three metal primers and one multi-mode
adhesive system on the shear bond strength (SBS) of a flowable composite resin to
nickel-chrome metal alloy (Ni-Cr). Ninety plates were cast from Ni-Cr and divided
in nine groups (n=10). The surfaces were sandblasted with Al2O3 and primed with
three adhesive primers: Alloy Primer (AP), Universal Primer (TP) and RelyX
Ceramic Primer (CP), and a multi-mode adhesive (Scotchbond Universal, SU). The
Adper Single Bond Plus (SB) and SU adhesives were also combined with adhesive
primers. Control group did not have any surface treatment. The groups were: AP,
AP+SB, AP+SU, TP+SB, TP+SU, CP+SB, CP+SU and SU. Composite cylinders were built
on alloy surface. After 24 h, half the specimens were subjected to SBS and the
other half to thermal cycling before testing. Data were analyzed by two-way ANOVA
and Tukey's test (a=0.05). Failure modes were assessed by SEM observation. Higher
SBS were obtained with AP and TP combined with adhesives at 24 h and the lowest
one for control group. Thermocycling reduced SBS for AP, CP+SU and SU.
Combination between TP and SU resulted in the highest SBS after the
thermocycling. TP groups showed all types of failures and high incidence of mixed
failures. The use of AP and UP metal primers before application of SU and SB
adhesive systems increased the SBS of composite to Ni-Cr. These combinations
between metal primers and adhesives had the highest SBS after thermocycling.
PMID- 28492753
TI - Effect of Erosion/Abrasion Challenge on the Dentin Tubule Occlusion Using
Different Desensitizing Agents.
AB - The aim of the study was to evaluate dentinal tubule occlusion, measuring the
dentin permeability (Lp) and using different desensitizing agents before and
after abrasive/erosive challenge. Dentin discs from 42 healthy human third molars
were obtained. Minimum Lp was measured after a smear layer simulation using #600
SiC paper and maximum Lp after an immersion in 0.5 M EDTA. The specimens were
treated with different desensitizers: two varnishes (Clinpro XT Varnish-CV, Fluor
Protector-FP), a paste (Desensibilize Nano P-NP) and a gel (Oxa Gel-OG). The Lp
of each specimen was measured immediately after the desensitizers' application.
The discs were subjected to erosion/abrasion cycles for 7 days, with 0.5% citric
acid solution (6x/day) and tooth brushing (3x/day). Lp was measured after the
first, fourth and seventh day of the challenge. The data were analyzed by 3-way
ANOVA with repeated measurements and by a Games-Howell test (alpha=5%). FP and CV
did not show significant differences in Lp immediately after application until
the 7th day (p<0.05). OG showed a significant increase in Lp after the 4th and
7th days. NP resulted in a significantly higher permeability compared to the
other materials immediately after the application and after the 1st day of
challenge. All the desensitizers reduced the dentin permeability immediately
after application. However, only the varnishes were able to maintain the
occlusive effect after the erosion/abrasion challenge.
PMID- 28492754
TI - Mandibular Protraction Appliance Effects in Class II Malocclusion in Children,
Adolescents and Young Adults.
AB - The aim of this study was to evaluate the effects of the mandibular protraction
appliance (MPA) for treating mild to moderate Class II malocclusion at different
stages of dentofacial development. Lateral radiographs were evaluated before (T0)
and at the end (T1) of orthodontic treatment with fixed appliance associated with
MPA. Sixty-five consecutively treated patients were divided according to the
stage of dentofacial development: 21 children in late mixed dentition, 22
adolescents and 22 young adults with full permanent dentition. The differences
between and within groups were analyzed by MANOVA at p<0.05. The correction of
anteroposterior discrepancy (Wits) was significantly reduced in all development
stages (p<0.01), with no difference between groups. Class II was corrected
predominantly by dental changes in the mandibular arch, with accentuated
proclination of the mandibular incisors and mesial displacement of mandibular
molars. The MPA had no skeletal effects in any of the groups, except for a mild
reduction of SNA (p=0.018) and ANB angles (p<0.0001) among the mixed dentition
children. With regard to soft-tissue profile, facial convexity decreased
significantly in all groups (p<0.01). In conclusion, the MPA associated with
fixed appliance corrected the Class II occlusion, basically by a mandibular arch
protrusion. A mild skeletal maxillary change was significant only when this
treatment protocol began during mixed dentition.
PMID- 28492755
TI - Association between Root Caries and Depressive Symptoms among Elders in Carlos
Barbosa, RS, Brazil.
AB - : The aim of this study was to evaluate the association between depressive
symptoms and root caries among independent-living older persons. All community
dwelling older adults (not hospitalized and not bedridden) living in Carlos
Barbosa, RS, Brazil, were invited to participate, and 785 completed the study
protocol (standardized questionnaire assessing socio-demographic information and
health behavior, Geriatric Depression Scale [GDS] - brief version, and oral
examination [DMFT-Root index, Visible Plaque Index and stimulated salivary
flow]). Out of them, 390 participants with at least one natural tooth were
included in the present analysis. The outcome of interest was the ratio between
the number of decayed roots and the number of roots at risk. The association
between independent variables (depression and socioeconomic aspects) and the
outcome was assessed using negative binomial regression models. RESULTS: The
final, fully adjusted model revealed that age (beta=0.03, p=0.001), female sex
(beta=-0.23, p=0.08), living in a rural area (beta=0.25, p=0.008), tooth brushing
frequency (beta=0.43, p=0.025) and stimulated salivary flow (beta=-0.012,
p<0.0001) were significantly associated with the presence of root caries. In
addition, the interaction between male sex and the presence of depression
symptoms (beta=-0.99, p=0.012) was also independently and significantly
associated with root caries. The interaction between male sex and depression
symptoms was associated with root caries, suggesting that psychological
mechanisms may be involved indirectly in the development of root caries in older
adults.
PMID- 28492756
TI - A Longitudinal Study of Early Childhood Caries and Associated Factors in
Brazilian Children.
AB - Early childhood caries (ECC) affects children all over the world and has high
prevalence and severity in preschool children. Different social, biological and
behavioral factors compose a network of causal factors for ECC. The aim was to
evaluate the association between socioeconomic variables and caries at baseline,
and the presence of Streptococcus mutans and Lactobacillus spp. microorganisms
with the progression of caries lesions after two years of follow-up in a group of
children. At baseline, 163 children (3-4 years old) living in the areas of 12
primary care services of the Hospital Group Conceicao (GHC, Porto Alegre, RS,
Brazil) were evaluated. After two years, 119 children were re-evaluated. Clinical
examinations were conducted by calibrated examiners using the ICDAS criteria. A
sociodemographic questionnaire was applied to the children's parents and saliva
samples were collected from the children for microbiological analysis.
Descriptive statistics and multivariate Poisson regression analysis were
performed in the statistical analysis. The factors associated with the caries
progression were marital status of mothers (p=0.040), higher S. mutans counts
(p=0.031) and the presence of cavitated lesions at baseline (p<0.001). The caries
lesions progression in preschool children enrolled in primary health care was
directly associated with marital status, presence of cavitated lesions at
baseline and higher S. mutans counts at two-year follow-up.
PMID- 28492757
TI - Meloxicam as a Radiation-Protective Agent on Mandibles of Irradiated Rats.
AB - This study evaluated the action of ionizing radiation and the possible
radioprotective effect of the non-steroidal anti-inflammatory drug meloxicam on
the bone physiology of rat mandibles by assessing the alveolar socket healing and
bone strength. Forty male Wistar rats were divided in 4 groups (n=10): control
(CG), irradiated (IG), meloxicam (MG), meloxicam irradiated (MIG). A dose of 0.2
mg/kg meloxicam was administered to MG and MIG. After this, IG and MIG were
irradiated with 15 Gy radiation dose in the mandible. Forty days after the above
procedures, the mandibular first molars were extracted and the animals were
killed after 15 or 30 days (n=5). Micro-computed tomography and bending test were
used to evaluate alveolar socket healing and bone strength, respectively. At 15
days, bone volume, bone volume fraction and trabecular thickness were higher in
the CG and MG than in the IG and MIG; and trabecular separation was higher in the
IG compared with the others. At 30 days, there was a difference only in
trabecular separation, which was higher in IG than in CG and MG, and MIG did not
differ from the others. Bone strength was lower in IG compared with CG and MG,
and MIG did not differ from the others. In conclusion, the ionizing radiation
affected the bone physiology of rat mandibles, delaying the alveolar socket
healing and reducing the bone strength. Moreover, the meloxicam had a positive
effect on the trabecular separation in alveolar socket healing and on the bone
strength.
PMID- 28492758
TI - Giant Epignathus Teratoma Discovered at Birth: A Case Report and 7-Year Follow
Up.
AB - Teratomas are tumors composed by tissues derived from the three germ cell layers,
and they are relatively uncommon in head and neck. The term epignathus has been
applied to teratomas from the oropharynx. This paper reports the case of a giant
epignathus teratoma discovered at birth, which was successfully managed and
followed up for 7 years. A newborn boy presented a polypoid tumor mass
exteriorizing through the mouth over a length of 9 cm, with some surface areas
resembling skin and others exhibiting hair. Computed tomography showed that the
mass arose deep from the left hemiface. Alpha-fetoprotein (AFP) levels were high
(316,000 ng/mL). Surgery was performed and microscopic analysis confirmed the
diagnosis of mature teratoma. Because of residual tumor and high AFP levels, the
patient was submitted to chemotherapy, resulting in complete regression of the
lesion and normalization of AFP levels. Surgical repair of a cleft palate was
performed at 5 years of age. At 7 years of age, the patient was in good general
health and showed no clinical signs of recurrence. Although epignathus is a rare
condition, it should be diagnosed in the fetus as early as possible. Prenatal
care provides unquestionable benefits, providing the early diagnosis of anomalies
that can jeopardize the life of the fetus and contributing to the indication of
cases that require treatment before birth.
PMID- 28492759
TI - Ameloblastic Fibrosarcoma: A Case Report and Literature Review.
AB - Here is described a case of ameloblastic fibrosarcoma (AFS) affecting the
posterior mandible of a woman who was treated surgically and recovered without
signs of recurrence or metastasis after 12 years of follow-up. Tumor sections
were immunostained for cell cycle, epithelial and mesenchymal markers.
Immunohistochemical analysis evidenced high Ki-67 positivity in stromal cells
(mean of 20.9 cells/High power field). Epithelial cells displayed strong
positivity for p53, p63 and cytokeratin 19. In addition to the case report, a
systematic review of current knowledge is presented on the AFS's clinical
demographic features and prognostic factors. Based on the review, 88/99 cases
were diagnosed as AFS, 9/99 as ameloblastic fibro-odontosarcoma and 2/99 as
ameloblastic fibrodentinosarcoma. All these lesions displayed very similar
clinical-demographic and prognostic features. Moreover, the review provided
evidence that first treatment, regional metastasis, distant metastasis and local
recurrence were significant prognostic values for malignant odontogenic
mesenchymal lesions. Based on the findings, segregation among ameloblastic
fibrosarcoma, ameloblastic fibrodentinosarcoma and ameloblastic fibro
odontosarcoma seems illogical, considering all these lesions have similar
predilections and outcomes.
PMID- 28492760
TI - Determinants of tobacco use by students.
AB - OBJECTIVE: Estimate the prevalence and determinants of tobacco use by students.
METHODS: This cross-sectional study, carried out between 2013 and 2014, evaluates
701 public school students between 10 and 79 years of age living in a city in the
countryside of the State of Goias, Midwest of Brazil. A structured questionnaire
collected the data and the predictor variables were demographic data, family
nucleus, religion, physical activity practice, family functionality and parental
smoking. Two multivariable models were implemented, the first for occasional
tobacco use and the second for regular use, acquiring the measure of prevalence
ratio (PR) and their respective 95%CI. Variables with p < 0.10 were included in
Poisson regression models with robust variance to obtain the adjusted PR (adPR)
and 95%CI. The Wald Chi-Squared test examined the differences between
proportions, and values with p < 0.05 were statistically significant. RESULTS:
The prevalence of occasional and regular tobacco use were 33.4% (95%CI 29.8-36.9)
and 6.7% (95%CI 5.0-8.8), respectively. The factors associated with occasional
tobacco consumption were age of 15 to 17 years (adPR = 1.98) and above 18 years
(adPR = 3.87), male gender (adPR = 1.23), moderate family dysfunction (adPR =
1.30), high family dysfunction (adPR = 1.97) and parental smoking (adPR = 1.60).
In regards to regular consumption of tobacco, age above 18 years (adPR = 4.63),
lack of religion (adPR = 2.08), high family dysfunction (adPR = 2.35) and
parental smoking (adPR = 2.89) remained associated. CONCLUSIONS: Students exhibit
a high prevalence of occasional and regular tobacco use. This consumption relates
to sociodemographic variables and family dysfunction. OBJETIVO: Estimar a
prevalencia e determinantes do consumo de tabaco por estudantes. METODOS: Neste
estudo de corte transversal, realizado entre 2013 e 2014, avaliamos 701
estudantes entre 10 e 79 anos de escolas publicas de um municipio do interior do
estado de Goias, Centro-Oeste do Brasil. Os dados foram coletados por meio de um
questionario estruturado, cujas variaveis preditoras foram: dados
sociodemograficos, nucleo familiar, religiao, pratica de atividade fisica,
funcionalidade familiar e pai ou mae fumante. Foram implementados dois modelos
multivariaveis, o primeiro para uso de tabaco na vida e o segundo para uso
regular, obtendo-se como medida de efeito razao de prevalencia (RP) e seus
respectivos IC95%. Variaveis com p < 0,10 foram incluidas em modelos de regressao
de Poisson com variancia robusta, para obtencao da RP ajustada (RPaj) e IC95%. O
teste Qui-quadrado de Wald foi utilizado para testar as diferencas entre as
proporcoes, e valores com p < 0,05 foram considerados estatisticamente
significantes. RESULTADOS: As prevalencias de consumo de tabaco na vida e regular
foram de 33,4% (IC95% 29,8-36,9) e 6,7% (IC95% 5,0-8,8), respectivamente. Os
fatores associados ao consumo de tabaco na vida foram: idade de 15 a 17 anos
(RPaj = 1,98) e superior a 18 anos (RPaj = 3,87), sexo masculino (RPaj = 1,23),
moderada disfuncionalidade familiar (RPaj = 1,30), elevada disfuncionalidade
familiar (RPaj = 1,97) e pai ou mae fumante (RPaj = 1,60). Em relacao ao consumo
regular de tabaco, permaneceram associados a idade superior a 18 anos (RPaj =
4,63), nao possuir religiao (RPaj = 2,08), elevada disfuncionalidade familiar
(RPaj = 2,35) e pai ou mae fumante (RPaj = 2,89). CONCLUSOES: Estudantes
apresentam elevada prevalencia de consumo de tabaco na vida e regular. Esse
consumo associa-se com variaveis sociodemograficas e disfuncionalidade familiar.
PMID- 28492761
TI - Hospitalization in older adults: association with multimorbidity, primary health
care and private health plan.
AB - OBJECTIVE: Evaluate the association of multimorbidity, primary health care model
and possession of a private health plan with hospitalization. METHODS: A
population-based cross-sectional study with 1,593 elderly individuals (60 years
old or older) living in the urban area of the city of Bage, State of Rio Grande
do Sul, Brazil. The outcome was hospitalization in the year preceding the
interview. The multimorbidity was evaluated through two cut-off points (>= 2 and
>= 3). The primary health care model was defined by residence in areas covered by
traditional care or by Family Health Strategy. The older adults mentioned the
possession of a private health plan. We performed a gross and adjusted analysis
by Poisson regression using a hierarchical model. The adjustment included
demographic, socioeconomic, functional capacity disability and health services
variables. RESULTS: The occurrence of overall and non-surgical hospitalization
was 17.7% (95%CI 15.8-19.6) and 10.6% (95%CI 9.1-12.1), respectively. Older
adults with multimorbidity were admitted to hospitals more often when to older
adults without multimorbidity, regardless of the exhibition' form of operation.
Having a private health plan increased the hospitalization by 1.71 (95%CI 1.09
2.69) times among residents in the areas of the Family Health Strategy when
compared to elderly residents in traditional areas without a private health plan.
CONCLUSIONS: The multimorbidity increased the occurrence of hospitalizations,
especially non-surgical ones. Hospitalization was more frequent in older adults
with private health plan and those living in Family Health Strategy areas,
regardless of the presence of multiple diseases. OBJETIVO: Avaliar a associacao
da multimorbidade, modelo de atencao basica e posse de plano de saude com
hospitalizacao. METODOS: Estudo transversal de base populacional com 1.593 idosos
(60 anos ou mais) residentes na zona urbana do municipio de Bage, Rio Grande do
Sul. O desfecho foi a hospitalizacao no ano anterior a entrevista. A
multimorbidade foi avaliada por meio de dois pontos de corte (>= 2 e >= 3). O
modelo de atencao basica foi definido pela residencia em areas cobertas pela
atencao tradicional ou da Estrategia Saude da Familia. A posse de plano de saude
foi referida pelos idosos. Realizou-se analise bruta e ajustada por regressao de
Poisson utilizando modelo hierarquizado. O ajuste incluiu variaveis demograficas,
socioeconomicas, capacidades funcionais e de servicos de saude. RESULTADOS: A
ocorrencia de hospitalizacao geral e nao cirurgica foi de 17,7% (IC95% 15,8-19,6)
e 10,6% (IC95% 9,1-12,1), respectivamente. Idosos com multimorbidade
hospitalizaram mais em comparacao com os idosos sem multimorbidade,
independentemente da forma de operacionalizacao da exposicao. O plano de saude
aumentou em 1,71 (IC95% 1,09-2,69) vezes a internacao hospitalar entre residentes
nas areas da Estrategia Saude da Familia em comparacao aos idosos residentes nas
areas tradicionais sem plano de saude. CONCLUSOES: A multimorbidade aumentou a
ocorrencia de hospitalizacoes, principalmente aquelas nao cirurgicas. Idosos com
plano de saude e residentes em areas de Estrategia Saude da Familia internaram
mais, independentemente da presenca de multiplas doencas.
PMID- 28492762
TI - Equity in out-of-pocket payment in Chile.
AB - OBJECTIVE: To assess the distribution of financial burden in Chile, with a focus
on the burden and progressivity of out-of-pocket payment. METHODS: Based on the
principle of ability to pay, we explore factors that contribute to inequities in
the health system finance and issues about the burden of out-of-pocket payment,
as well as the progressivity and redistributive effect of out-of-pocket payment
in Chile. Our analysis is based on data from the 2006 National Survey on
Satisfaction and Out-of-Pocket Payments. RESULTS: Results from this study
indicate evidence of inequity, in spite of the progressivity of the healthcare
system. Our analysis also identifies relevant policy variables such as education,
insurance system, and method of payment that should be taken into consideration
in the ongoing debates and research in improving the Chilean system. CONCLUSIONS:
In order to reduce the detected disparities among income groups, healthcare
priorities should target low-income groups. Furthermore, policies should explore
changes in the access to education and its impact on equity.
PMID- 28492763
TI - Sociodemographic and health factors associated with mortality in community
dwelling elderly.
AB - OBJECTIVE: The objective of this study is to identify factors associated with
mortality, with emphasis on gender and age differences. METHODS: This is a cross
sectional study, which uses data from the FIBRA-2008-2009 network in Campinas,
State of Sao Paulo, Brazil, with information on non-institutionalized residents
of the urban area and the Mortality Information System. The dependent variable
has been death, in 2013. The associations have been tested by odds ratio (OR) and
their 95% confidence intervals, and the analyses have been conducted using the
program Stata 12.0. RESULTS: Average age has been 72.3 years, 69.3% have been
women, and 8.9% have died. We have found greater OR for mortality in individuals
aged >= 75 years, classified as pre-frail or frail, and in those who have
reported heart disease. CONCLUSIONS: In this study, the analysis of specific
subgroups has allowed us to better understand the relationship between the
factors associated with death in the elderly. With the exception of age,
strategies based on primary and secondary care, focused on priority groups, can
have a positive impact on the reduction of mortality among the elderly. OBJETIVO:
Identificar fatores associados a mortalidade, com enfase nas diferencas de genero
e idade. METODOS: Trata-se de estudo transversal, utilizando dados provenientes
da rede FIBRA-2008-2009 em Campinas, SP, com informacoes de pessoas nao
institucionalizadas residentes na area urbana e pelo Sistema de Informacoes de
Mortalidade. A variavel dependente foi a ocorrencia de obito, verificada em 2013.
As associacoes foram testadas pelas razoes de chances (OR) e respectivos
intervalos de confianca de 95%, e as analises conduzidas no programa Stata 12.0.
RESULTADOS: A media de idade foi 72,3 anos, 69,3% eram mulheres e 8,9% foram a
obito. Encontrou-se maior OR para mortalidade nos individuos com idade >= 75
anos, nos classificados como pre-fragil ou fragil e naqueles que referiram doenca
do coracao. CONCLUSOES: Neste estudo, a analise para os subgrupos especificos
permitiu melhor compreender a relacao entre fatores que se associam ao obito no
idoso. Com excecao da idade, estrategias baseadas no cuidado especifico de
atencao primaria e secundaria, direcionadas a grupos prioritarios, podem ter um
impacto positivo na reducao da mortalidade entre os idosos.
PMID- 28492765
TI - Epidemiology and Health Services: journal of the Brazilian National Health System
is classified B2 for Public Health at Qualis/Capes.
PMID- 28492764
TI - Measuring the quality of life in hypertension according to Item Response Theory.
AB - OBJECTIVE: To analyze the Miniquestionario de Qualidade de Vida em Hipertensao
Arterial (MINICHAL - Mini-questionnaire of Quality of Life in Hypertension) using
the Item Response Theory. METHODS: This is an analytical study conducted with 712
persons with hypertension treated in thirteen primary health care units of
Fortaleza, State of Ceara, Brazil, in 2015. The steps of the analysis by the Item
Response Theory were: evaluation of dimensionality, estimation of parameters of
items, and construction of scale. The study of dimensionality was carried out on
the polychoric correlation matrix and confirmatory factor analysis. To estimate
the item parameters, we used the Gradual Response Model of Samejima. The analyses
were conducted using the free software R with the aid of psych and mirt. RESULTS:
The analysis has allowed the visualization of item parameters and their
individual contributions in the measurement of the latent trait, generating more
information and allowing the construction of a scale with an interpretative model
that demonstrates the evolution of the worsening of the quality of life in five
levels. Regarding the item parameters, the items related to the somatic state
have had a good performance, as they have presented better power to discriminate
individuals with worse quality of life. The items related to mental state have
been those which contributed with less psychometric data in the MINICHAL.
CONCLUSIONS: We conclude that the instrument is suitable for the identification
of the worsening of the quality of life in hypertension. The analysis of the
MINICHAL using the Item Response Theory has allowed us to identify new sides of
this instrument that have not yet been addressed in previous studies. OBJETIVO:
Analisar o Miniquestionario de Qualidade de Vida em Hipertensao Arterial
(MINICHAL) por meio da Teoria da Resposta ao Item. METODOS: Estudo analitico
realizado com 712 pessoas com hipertensao arterial atendidas em 13 unidades de
atencao primaria em saude de Fortaleza, CE, em 2015. As etapas da analise pela
Teoria da Resposta ao Item foram: avaliacao da dimensionalidade, estimacao dos
parametros dos itens e construcao da escala. O estudo da dimensionalidade foi
realizado sobre a matriz de correlacao policorica e analise fatorial
confirmatoria. Para a estimacao dos parametros dos itens, foi utilizado o Modelo
de Resposta Gradual de Samejima. As analises foram conduzidas no software livre R
com o auxilio dos pacotes psych e mirt. RESULTADOS: A analise permitiu a
visualizacao dos parametros dos itens e suas contribuicoes individuais na
mensuracao do traco latente, gerando mais informacao, permitindo a construcao de
uma escala com um modelo interpretativo que demonstra a evolucao da piora da
qualidade de vida em cinco niveis. Quanto aos parametros dos itens, houve bom
desempenho daqueles referentes ao estado somatico, pois apresentaram melhor poder
de discriminar os individuos com pior qualidade de vida. Os itens relacionados ao
estado mental foram os que contribuiram com menor quantidade de informacao
psicometrica no MINICHAL. CONCLUSOES: Conclui-se que o instrumento e indicado
para a identificacao da deterioracao da qualidade de vida em hipertensao
arterial. A analise do MINICHAL pela Teoria da Resposta ao Item permitiu
identificar novas facetas desse instrumento ainda nao abordadas em estudos
anteriores.
PMID- 28492766
TI - Clinical-epidemiological description of live births with microcephaly in the
state of Sergipe, Brazil, 2015.
AB - OBJECTIVE: to describe the clinical and epidemiological characteristics of
microcephaly cases in live births in Sergipe, Brazil, and to calculate the
prevalence in its municipalities. METHODS: this is a descriptive study on live
births from September 1st to November 30th, 2015, with data from medical records
and interviews with mothers. RESULTS: 83 cases of microcephaly were confirmed,
with three deaths; prevalence in the 26 municipalities with confirmed cases
ranged from 18 to 185/10,000 live births; the median of head circumference was 31
cm (range: 22.5-33.0); agenesis of corpus callosum (26/43), lissencephaly
(12/43), absence of midline (10/43) and ventriculomegaly (8/43) were observed in
the transfontanellar ultrasound; 40 mothers reported rash in pregnancy, 23 in the
first trimester, with pruritus, arthralgia and headache; seven were positive for
infections potentially causing malformations. CONCLUSION: there was a high
occurrence of cases of microcephaly, and reports of signs and symptoms compatible
with Zika virus infection during pregnancy.
PMID- 28492767
TI - Syphilis in pregnancy and congenital syphilis in Palmas, Tocantins State, Brazil,
2007-2014.
AB - OBJECTIVE: to describe the epidemiological profile of reported cases of syphilis
in pregnant women and congenital syphilis in the period 2007-2014 in Palmas-TO,
Brazil. METHODS: this is a descriptive study with data from the Information
System for Notifiable Diseases (Sinan). RESULTS: 171 pregnant women with syphilis
(4.7/1,000 live births [LB]) and 204 cases of congenital syphilis (5.6/1,000 LB)
were identified; most women were brown-skinned (71.3%), had low education level
(48.0%) and received late diagnosis during prenatal care (71.9%); the incidence
of congenital syphilis varied from 2.9 to 8.1/1,000 LB in the period; the
predominant maternal characteristics were age from 20 to 34 years (73.5%), having
up to complete high school (85.3%), attending prenatal care (81.4%), diagnosis of
syphilis during prenatal care (48.0%), and untreated partners of mothers who
attended prenatal care (83.0%), reaching almost 80% of live births with
congenital syphilis. CONCLUSION: it is necessary to adopt new strategies for the
effectiveness of the prenatal care provided, and, consequently, to reduce the
incidence of congenital syphilis.
PMID- 28492768
TI - Coverage trends of the Information System on Live Births in Mato Grosso, Brazil,
2000 to 2012.
AB - OBJECTIVE: to analyze the coverage trends of the Brazilian Information System on
Live Births (Sinasc) in the state of Mato Grosso and its Health Regions, in the
period from 2000 to 2012. METHODS: this is a time series study, coverage was
calculated by the ratio between the number of live births registered in the
system and the number estimated by the Brazilian Institute of Geography and
Statistics (IBGE); the trends were analyzed using polynomial regression models.
RESULTS: Sinasc coverage in Mato Grosso in the studied period presented
increasing trend, with a median of 94.9%; Araguaia Xingu region presented
coverage lower than 90% in the period; most of the regions presented coverage
increasing trends, except for Baixada Cuiabana, Centro Norte and Vale do Peixoto.
CONCLUSION: Sinasc coverage in Mato Grosso was satisfactory and has been
increasing in most of Health Regions.
PMID- 28492769
TI - Census of the Primary Health Care structure in Brazil (2012): potential coverage
estimates.
AB - OBJECTIVE: to estimate and discuss selected indicators of Primary Health Care
(PHC) structure in Brazil in 2012. METHODS: a descriptive ecological study was
carried out using Primary Health Care Centre census data from the National
Program for Access and Quality Improvement in Primary Care (PMAQ-AB); potential
coverage indicators were estimated for infrastructure, health team composition
and services available. RESULTS: the results revealed high coverage (>=70%) in
Brazil for Community Health Agents (87.6%), teams providing care 5 days or more a
week (71.4%), in 2 or more daily periods (70%), with nursing care services
(70.9%) and dressing changes (70.4%); on the other hand, coverage is still poor
(<=30%) for teams in health centres with adequate external signage (25.4%),
delivering care at the weekend (28.4%) and reception of service users by health
professionals (10.4%). CONCLUSION: the findings of this study point to the great
inequalities between Brazilian states in potential coverage as shown by APS
structure indicators.
PMID- 28492770
TI - Descriptive study on the evolution of hospitalization costs for ambulatory care
sensitive conditions in Brazil, 2000-2013.
AB - OBJECTIVE: to analyze the proportions of costs of hospitalizations for ambulatory
care sensitive conditions (ACSC) in relation to total hospitalization costs
funded by the Brazilian National Health System (SUS) in Brazil, in 2000, 2005,
2010 and 2013, according to sex, age and group of causes. METHODS: this is a
descriptive study, with data from SUS Hospital Information System (SIH/SUS); the
proportion of hospitalization costs for ACSC was estimated in relation to total
hospitalization costs. RESULTS: proportions decreased from 23.6% (2000) to 17.4%
(2013); higher rates occurred among women (29.8%), children (42.3%) and the
elderly (31.7%); on the other hand, there was a significant increase in the
proportion of hospitalization costs for angina (237.5%) and pneumonia (84.3%).
CONCLUSION: there were greater reductions in costs among children, elderly and
women; however, the persistence of high proportion of costs attributed to
cardiovascular diseases stands out, especially hospitalizations for angina.
PMID- 28492771
TI - Functional disability indicators and associated factors in the elderly: a
population-based study in Bage, Rio Grande do Sul, Brazil.
AB - OBJECTIVE: to estimate the prevalence of functional disability in basic and
instrumental daily activities and associated factors in elderly who live in the
urban area of Bage-RS, Brazil. METHODS: this is a population-based cross
sectional study, conducted in 2008; functional disability was defined by basic
and instrumental daily activities, using Katz index and Lawton and Brody scale;
Poisson regression was used for crude and adjusted analyses. RESULTS: 1,593
elderly individuals were investigated; the prevalence of disability for basic
activities was of 10.6% (95%CI: 9.1;12.1) and of 34.2% (95%CI: 31.9;36.6) for
instrumental activities; both disabilities were statistically associated to the
increment of age, low education level, alcohol consumption, history of
cerebrovascular diseases, cognitive impairment, hospitalization and home care.
CONCLUSION: a high proportion of elderly presented functional disability; the
outcomes were associated to the following variables: demographic, socioeconomic,
behavioral, health status and use of health services.
PMID- 28492772
TI - Life and health conditions among elderly: results of the EpiFloripa Idoso cohort
study.
AB - OBJECTIVE: to identify sociodemographic, behavioral and health changes in a
follow-up of participants in the health survey EpiFloripa Idoso. METHODS: this is
a population-based longitudinal study with elderly individuals in Florianopolis
SC, Brazil. RESULTS: 1,702 elderly individuals were interviewed in 2009-2010 and
1,197 in 2013-2014 (response rate: 89.1% and 70.2%, respectively); among followed
up individuals, most of them remained with a partner (53.4%), living with other
people (76.0%), not working (78.0%), with positive health perception (44.0%), not
using the Internet (67.5%), not smoking (57.5%), not consuming alcohol (53.3%),
not physically active (56.3%), consuming <5 servings of fruits/vegetables
(57.3%), independent (60.5%), overweight (47.0%), with negative screening for
cognitive impairment (69.4%), with no depressive symptoms (72.0%) and not having
suffered falls (60.6%). CONCLUSION: most elderly did not show significant changes
in their sociodemographic, behavioral and health characteristics; the need to
rethink more effective actions to improve the elderly health stands out.
PMID- 28492773
TI - Prevalence and associated factors of self-medication in adults living in the
Federal District, Brazil: a cross-sectional, population-based study.
AB - OBJECTIVE: to assess the prevalence of self-medication and to investigate its
associated factors in adults living in the Federal District, Brazil. METHODS:
this is a cross-sectional population-based study conducted with adults selected
through probabilistic sampling; self-medication prevalence was obtained from
those who reported having used any medicine in the previous seven days; Poisson
regression model with robust variance was applied to adjust the prevalence
ratios. RESULTS: 1,820 individuals were interviewed, of which 646 had taken at
least one medicine; self-medication prevalence was of 14.9% (95%CI: 12.6%;17.5%);
the adjusted analysis showed negative association in people aged 50 to 65 years
(PR=0.26; 95%CI: 0.15;0.47) and with chronic diseases (PR=0.38; 95%CI:
0.28;0.51); adults with difficulties in performing daily activities (PR=2.25;
95%CI: 1.43;3.53) practiced more self-medication. CONCLUSION: self-medication was
associated to young adults and those with problems in performing daily
activities.
PMID- 28492774
TI - The burden of cardiovascular diseases in Santa Catarina State, Brazil, in 2009.
AB - OBJECTIVE: to estimate the burden of cardiovascular diseases in Santa Catarina
State, Brazil. METHODS: this is an ecological study with the nine health
macroregions of the state as units of analysis; the number of years of life lost,
the number of years lived with disability and the number disability-adjusted life
years (DALYs) for 2009 were estimated. RESULTS: a total of 358,777 DALYs were
estimated, with a rate of 5,852 DALYs/100,000 inhabitants, 51.1% in males; age
groups with the highest rates were 45-59, 60-69, and 70-79 years; diseases that
most contributed to the DALYs were ischemic heart diseases and cerebrovascular
diseases; health regions with the highest DALYs rates were Planalto Norte, Sul
and Serra Catarinense. CONCLUSION: the high burden of cardiovascular diseases in
Santa Catarina shows the need to intensify actions of health promotion and
prevention in all regions of the state.
PMID- 28492775
TI - Laboratory Environment Management System - GAL: Assessment of a tool for sentinel
surveillance of influenza-like illness, Brazil, 2011-2012.
AB - OBJECTIVE: to evaluate the Brazilian Laboratorial Environment Management System
(GAL) as a data source for the Sentinel Surveillance of Influenza-Like Illness
(SSILI). METHODS: this is an evaluation study of GAL, through the analysis of its
simplicity, flexibility, data quality, acceptability, representativeness,
timeliness, stability and usefulness for SSILI, based on the guide for system
evaluation in public health of the Centers for Disease Control and Prevention
(Atlanta/GA, USA). RESULTS: in 2011 and 2012, a total of 13,765 exams for
respiratory viruses were registered. GAL presented simple structure, flexibility
to changes, good data quality, acceptability and timeliness in the access to test
results, being representative and stable in 23 Brazilian states. CONCLUSION: the
system is useful in meeting the goals of SSILI; however, there are some
recommendations for adjustments and for encouraging the adherence by the states
that do not use the system yet.
PMID- 28492776
TI - Tuberculosis mortality in Brazilian capitals, 2008-2010.
AB - OBJECTIVE: to analyze the association between tuberculosis mortality and socio
demographics and health indicators in the capitals of Brazilian states and the
Federal District. METHODS: this is an ecological study whose outcome was the
standardized coefficient of tuberculosis mortality in the 2008-2010 period; the
independent variables comprised 16 indicators, grouped into three blocks; Pearson
correlation test and multiple linear regression were applied for analysis.
RESULTS: 4,744 deaths from tuberculosis were registered in the 27 municipalities
(2.7 deaths per 100,000 inhabitants); the following indicators were associated
with tuberculosis mortality (p<0.10): income inequality (Gini index of monthly
income of individuals over 10 years old: beta=0.454; 95%CI 6.21;28.51),
proportion of migrants in the municipality (beta=0.537 95%CI 0.12;0.31), poor
black-skinned individuals (beta=0.302 95%CI 0.004;0.109) and coefficient of
Tb/HIV coinfection (beta=0.449 95%CI 0.05;0.28). CONCLUSION: tuberculosis
mortality was higher in capitals with greater income inequality, migration,
poverty among black-skinned individuals and occurrence of Tb/HIV coinfection.
PMID- 28492777
TI - Tuberculosis and diabetes: probabilistic linkage of databases to study the
association between both diseases.
AB - OBJECTIVE: to describe the profile of cases of tuberculosis and diabetes
comorbidity in Brazil. METHODS: this is a descriptive study with data from the
Brazilian Information System for Notifiable Diseases - tuberculosis (Sinan-TB)
and from the System of Registration and Monitoring of Hypertension and Diabetes
Mellitus (Hiperdia), from 2007 to 2011; probabilistic linkage was carried out
with Reclink software. RESULTS: 24,443 cases of comorbidity were found, including
3,181 cases not registered on Sinan-TB; of the total number of recovered cases,
mostly were males (57.2%), aged 40-59 years (52.3%), black/brown-skinned (68.4%),
with five to eight years of schooling (78.4%), with no regular use of alcohol
(86.5%) and negative serology for the HIV virus (91.8%). CONCLUSION: the cases
found had similar profile to those registered on Sinan-TB and the probabilistic
linkage of data from different information systems enabled the detection of cases
not captured by surveillance.
PMID- 28492778
TI - Sociodemographic, clinical and epidemiological aspects of Tuberculosis treatment
abandonment in Pernambuco, Brazil, 2001-2014.
AB - OBJECTIVE: to describe abandonment rates according to sociodemographic, clinical
and epidemiological characteristics of new tuberculosis cases being treated in
Pernambuco State, Brazil. METHODS: this is a descriptive ecological study using
data from the Information System for Notifiable Diseases from 2001 to 2014; the
abandonment rate was calculated by the Regional Administration on Health (GERES).
RESULTS: of the 57,015 new cases, 6,474 (11.3%) abandoned treatment, although
abandonment decreased from 16.4% (2001) to 9.3% (2014); the abandonment rate in
GERES I Recife, III Palmares, IV Caruaru, VIII Petrolina and IX Ouricuri was
still >5% in 2014; the rate was higher in males (11.9%), people aged 20-39
(12.7%), people with incomplete elementary school (12.1%), black-skinned people
(13.7%), institutionalized people (12.5%) and those with pulmonary +
extrapulmonary tuberculosis (14.1%). CONCLUSION: despite the decrease, the
abandonment rate remained high; males, adults with low education level, black
skinned people, institutionalized patients and patients with pulmonary +
extrapulmonary tuberculosis seemed more prone to abandoning treatment.
PMID- 28492779
TI - Prevalence of Kaposi's sarcoma in patients with AIDS and associated factors, Sao
Paulo-SP, Brazil, 2003-2010.
AB - OBJECTIVE: to estimate the prevalence of Kaposi's sarcoma (KS) in patients with
AIDS and identify the associated factors to the occurrence of this neoplasm.
METHODS: this is a cross-sectional study with notification data from two AIDS
reference centers in Sao Paulo-SP, Brazil, from January, 2003 to March, 2010;
probabilistic linkage and multiple logistic regression methods were applied.
RESULTS: among 3,557 AIDS cases, 213 (6%) presented KS; 95.3% of them occurred in
males; male sex (OR=3.1; 95%CI=1.4;6.6), age at the AIDS diagnosis >28 years old
(OR=1.6; 95%CI=1.0;2.6), MSM (OR=3.2; 95%CI=2.0;4.9), prior use of HAART (OR=0.4;
95%CI=0.3;0.5), AIDS diagnosis between 2007-2010 (OR=0.3; 95%CI=0.2;0.4), and
CD4+ T-cell counting under 200cells/mm3 (OR=16.0; 95%CI=6.0;42.7) and 200
500cells/mm3 (OR=2,5; 95%CI=1.1;6.4) were associated to the occurrence of KS.
CONCLUSION: KS has a high prevalence in Sao Paulo-SP; strategies for early HIV
diagnosis may reduce this prevalence.
PMID- 28492780
TI - [Epidemiological profile of traffic accidents in Marilia, Sao Paulo State,
Brazil, 2012].
AB - OBJECTIVE: to describe the profile of victims of traffic accidents and traffic
related deaths in Marilia-SP, Brazil. METHODS: this is a descriptive study, based
on data from police reports (PR) and Death Certificates (DC), in 2012. RESULTS:
1,537 PR were gathered; among the 3,257 individuals involved in traffic
accidents, 67.3% were men, and 53.3% were between 20-39 years of age; most
accidents occurred on road intersections (35.2%), at 8 a.m. (6.8%), 1 p.m. (7.2%)
and 7 p.m. (8.1%); motorcycle was the most involved vehicle in the accidents
(47.6%); among the 78 deaths reported, 61 were men, 31 were over 50 years old,
and 23 were motorcyclists; 32 fatal accidents occurred on highways. Conclusion:
the main victims and fatal victims of traffic accidents were male motorcyclists;
fatal accidents occurred mainly on highways, and the main victims were over 50
years old.
PMID- 28492781
TI - Evaluation of knowledge about the Human Papilloma Virus (HPV) and its vaccination
among Community Health Agents in the municipality of Tubarao, Santa Catarina,
Brazil, in 2014.
AB - OBJECTIVE: to evaluate the knowledge of Community Health Agents (CHA) about the
Human Papilloma Virus (HPV) and its vaccination. METHODS: this is a cross
sectional study with CHA who worked in Tubarao-SC, Brazil, in 2014; data were
collected through an evaluation tool about HPV and its vaccination, validated for
English language and translated and adapted into Portuguese. RESULTS: 124 CHA
participated in this study; all of them had already heard about HPV, but only
25.0% had heard about HPV testing; 72.6% answered correctly less than 70.0% of
the questions; those who answered correctly more than 70.0% were, in general,
younger than the other CHA (p=0.010). CONCLUSION: CHA demonstrated little
knowledge on HPV, which may affect their work as multipliers in the prevention of
diseases and in education in health.
PMID- 28492782
TI - [Outbreak of nephritis by Streptococcus equi subspecies zooepidemicus: case
control study in the municipality of Monte Santo de Minas, Minas Gerais, Brazil,
2013].
AB - OBJECTIVE: to investigate an outbreak of nephritis by Streptococcus zooepidemicus
in Monte Santo de Minas, Minas Gerais State, Brazil. METHODS: a case-control
study and attempt to isolate the bacterial agent were carried out from January to
April 2013, using clinical and laboratory data, interviews and inspections.
RESULTS: 417 suspected cases were reported, of which 175 (42.0%) were confirmed;
90.9% lived in that municipality, of which 67.4% were female, with median age of
36 years; 24% of cases were hospitalized; three ice cream shops in the
municipality used type A milk; there was significant association between the
illness and the consumption of type A milk (odds ratio [OR]=4.16/95%CI:
1.55;11.18), one of the ice cream made with this milk (OR=3.09/95%CI: 1.39;6.86)
and milk shake of non-processed milk (OR=3.25/95%CI: 1.13;9.36); the bacterium
was not detected in rural properties. CONCLUSION: the outbreak of nephritis by
Streptococcus zooepidemicus was associated with the consumption of milk and dairy
products.
PMID- 28492783
TI - Infant mortality surveillance in Recife, Pernambuco, Brazil: operationalization,
strengths and limitations.
AB - OBJECTIVE: to report the experience on infant mortality surveillance (IMS) in the
municipality of Recife-PE, Brazil. METHODS: a documentary research and a query
with key-informants who participated in the implementation and consolidation of
the IMS were conducted; data of the Mortality Information System (SIM) and of the
surveillance worksheets were used to measure the coverage of the investigated
deaths. RESULTS: the implementation of the IMS has occurred gradually since 2003;
the strategy is composed by (i) identification of deaths, (ii) investigation,
(iii) discussion, (iv) recommendations and correction of vital statistics; upon
completion of implementation (2006), 98.5% (256) of the deaths had been
investigated and discussed, with the participation of those involved in the
cases; in 2015, this coverage corresponded to 97.7%. CONCLUSION: the main
recommendations consisted of expanding the access, coverage and improvement of
primary, secondary and tertiary care quality; IMS is able to support changes in
health care practices, as well as planning and organization of maternal and child
care.
PMID- 28492784
TI - Budget impact analysis.
PMID- 28492785
TI - Union Generates Success.
PMID- 28492786
TI - The Brazilian Registry of Adult Patient Undergoing Cardiovascular Surgery, the
BYPASS Project: Results of the First 1,722 Patients.
AB - Objective: To report the early results of the BYPASS project - the Brazilian
registrY of adult Patient undergoing cArdiovaScular Surgery - a national,
observational, prospective, and longitudinal follow-up registry, aiming to chart
a profile of patients undergoing cardiovascular surgery in Brazil, assessing the
data harvested from the initial 1,722 patients. Methods: Data collection involved
institutions throughout the whole country, comprising 17 centers in 4 regions:
Southeast (8), Northeast (5), South (3), and Center-West (1). The study
population consists of patients over 18 years of age, and the types of operations
recorded were: coronary artery bypass graft (CABG), mitral valve, aortic valve
(either conventional or transcatheter), surgical correction of atrial
fibrillation, cardiac transplantation, mechanical circulatory support and
congenital heart diseases in adults. Results: 83.1% of patients came from the
public health system (SUS), 9.6% from the supplemental (private insurance)
healthcare systems; and 7.3% from private (out-of -pocket) clinic. Male patients
comprised 66%, 30% were diabetics, 46% had dyslipidemia, 28% previously sustained
a myocardial infarction, and 9.4% underwent prior cardiovascular surgery.
Patients underwent coronary artery bypass surgery were 54.1% and 31.5% to valve
surgery, either isolated or combined. The overall postoperative mortality up to
the 7th postoperative day was 4%; for CABG was 2.6%, and for valve operations,
4.4%. Conclusion: This first report outlines the consecution of the Brazilian
surgical cardiac database, intended to serve primarily as a tool for providing
information for clinical improvement and patient safety and constitute a basis
for production of research protocols.
PMID- 28492787
TI - Validation of German Aortic Valve Score in a Multi-Surgeon Single Center.
AB - OBJECTIVE:: Risk assessment for operative mortality is mandatory for all cardiac
operations. For some operation types such as aortic valve repair, EuroSCORE II
overestimates the mortality rate and a new scoring system (German AV score) has
been developed for a more accurate assessment of operative risk. In this study,
we aimed to validate German Aortic Valve Score in our clinic in patients
undergoing isolated aortic valve replacement. METHODS:: A total of 35 patients
who underwent isolated open aortic valve replacement between 2010 and 2013 were
included. Patients with concomitant procedures and transcatheter aortic valve
implantation were excluded. Patients' data were collected and analyzed
retrospectively. Patients' risk scores EuroSCORE II were calculated online
according to criteria described by EuroSCORE taskforce, Aortic Valve Scores were
also calculated. RESULTS:: The mean age of patients was 61.14+/-13.25 years
(range 29-80 years). The number of female patients was 14 (40%) and body mass
index of 25 (71.43%) patients was in range of 22-35. Mean German Aortic Valve
Score was 1.05+/-0.96 (min: 0 max: 4.98) and mean EuroSCORE was 2.30+/-2.60 (min:
0.62, max: 2.30). The Aortic Valve Score scale showed better discriminative
capacity (AUC 0.647, 95% CI 0.439-0.854). The goodness of fit was x2HL=16.63;
P=0.436). EuroSCORE II scale had shown less discriminative capacity (AUC 0.397,
95% CI 0.200-0.597). The goodness of fit was good for both scales. The goodness
of fit was x2HL=30.10; P=0.610. CONCLUSION:: In conclusion, German AV score
applies to our population with high predictive accuracy and goodness of fit.
PMID- 28492788
TI - Hemoglobin A1c Levels Predicts Acute Kidney Injury after Coronary Artery Bypass
Surgery in Non-Diabetic Patients.
AB - INTRODUCTION:: Elevated hemoglobin A1c levels in patients with diabetes mellitus
have been known as a risk factor for acute kidney injury after coronary artery
bypass grafting. However, the relationship between hemoglobin A1c levels in non
diabetics and acute kidney injury is under debate. We aimed to investigate the
association of preoperative hemoglobin A1c levels with acute kidney injury in non
diabetic patients undergoing isolated coronary artery bypass grafting. METHODS::
202 non-diabetic patients with normal renal function (serum creatinine <1.4
mg/dl) who underwent isolated coronary bypass were analyzed. Hemoglobin A1c level
was measured at the baseline examination. Patients were separated into two groups
according to preoperative Hemoglobin A1c level. Group 1 consisted of patients
with preoperative HbA1c levels of < 5.6% and Group 2 consisted of patients with
preoperative HbA1c levels of >= 5.6%. Acute kidney injury diagnosis was made by
comparing baseline and postoperative serum creatinine to determine the presence
of predefined significant change based on the Kidney Disease Improving Global
Outcomes (KDIGO) definition. RESULTS:: Acute kidney injury occurred in 19 (10.5%)
patients after surgery. The incidence of acute kidney injury was 3.6% in Group 1
and 16.7% in Group 2. Elevated baseline hemoglobin A1c level was found to be
associated with acute kidney injury (P=0.0001). None of the patients became
hemodialysis dependent. The cut off value for acute kidney injury in our group of
patients was 5.75%. CONCLUSION:: Our findings suggest that, in non-diabetics,
elevated preoperative hemoglobin A1c level may be associated with acute kidney
injury in patients undergoing coronary artery bypass grafting. Prospective
randomized studies in larger groups are needed to confirm these results.
PMID- 28492789
TI - Single-Dose Lignocaine-Based Blood Cardioplegia in Single Valve Replacement
Patients.
AB - OBJECTIVE:: Myocardial protection is the most important in cardiac surgery. We
compared our modified single-dose long-acting lignocaine-based blood cardioplegia
with short-acting St Thomas 1 blood cardioplegia in patients undergoing single
valve replacement. METHODS:: A total of 110 patients who underwent single (aortic
or mitral) valve replacement surgery were enrolled. Patients were divided in two
groups based on the cardioplegia solution used. In group 1 (56 patients), long
acting lignocaine based-blood cardioplegia solution was administered as a single
dose while in group 2 (54 patients), standard St Thomas IB (short-acting blood
based cardioplegia solution) was administered and repeated every 20 minutes. All
the patients were compared for preoperative baseline parameters, intraoperative
and all the postoperative parameters. RESULTS:: We did not find any statistically
significant difference in preoperative baseline parameters. Cardiopulmonary
bypass time were 73.8+/-16.5 and 76.4+/-16.9 minutes (P=0.43) and cross clamp
time were 58.9+/-10.3 and 66.3+/-11.2 minutes (P=0.23) in group 1 and group 2,
respectively. Mean of maximum inotrope score was 6.3+/-2.52 and 6.1+/-2.13
(P=0.65) in group 1 and group 2, respectively. We also did not find any
statistically significant difference in creatine-phosphokinase-MB (CPK-MB),
Troponin-I levels, lactate level and cardiac functions postoperatively.
CONCLUSION:: This study proves the safety and efficacy of long-acting lignocaine
based single-dose blood cardioplegia compared to the standard short-acting multi
dose blood cardioplegia in patients requiring the single valve replacement.
Further studies need to be undertaken to establish this non-inferiority in
situations of complex cardiac procedures especially in compromised patients.
PMID- 28492791
TI - Respiratory Muscle Training Improves Diaphragm Citrate Synthase Activity and
Hemodynamic Function in Rats with Heart Failure.
AB - INTRODUCTION:: Enhanced respiratory muscle strength in patients with heart
failure positively alters the clinical trajectory of heart failure. In an
experimental model, respiratory muscle training in rats with heart failure has
been shown to improve cardiopulmonary function through mechanisms yet to be
entirely elucidated. OBJECTIVE:: The present report aimed to evaluate the
respiratory muscle training effects in diaphragm citrate synthase activity and
hemodynamic function in rats with heart failure. METHODS:: Wistar rats were
divided into four experimental groups: sedentary sham (Sed-Sham, n=8), trained
sham (RMT-Sham, n=8), sedentary heart failure (Sed-HF, n=7) and trained heart
failure (RMT-HF, n=7). The animals were submitted to a RMT protocol performed 30
minutes a day, 5 days/week, for 6 weeks. RESULTS:: In rats with heart failure,
respiratory muscle training decreased pulmonary congestion and right ventricular
hypertrophy. Deleterious alterations in left ventricular pressures, as well as
left ventricular contractility and relaxation, were assuaged by respiratory
muscle training in heart failure rats. Citrate synthase activity, which was
significantly reduced in heart failure rats, was preserved by respiratory muscle
training. Additionally, a negative correlation was found between citrate synthase
and left ventricular end diastolic pressure and positive correlation was found
between citrate synthase and left ventricular systolic pressure. CONCLUSION::
Respiratory muscle training produces beneficial adaptations in the diaphragmatic
musculature, which is linked to improvements in left ventricular hemodynamics and
blood pressure in heart failure rats. The RMT-induced improvements in cardiac
architecture and the oxidative capacity of the diaphragm may improve the clinical
trajectory of patients with heart failure.
PMID- 28492790
TI - Effects of Low-Dose Recombinant Human Brain Natriuretic Peptide on Anterior
Myocardial Infarction Complicated by Cardiogenic Shock.
AB - INTRODUCTION:: The mortality due to cardiogenic shock complicating acute
myocardial infarction (AMI) is high even in patients with early
revascularization. Infusion of low dose recombinant human brain natriuretic
peptide (rhBNP) at the time of AMI is well tolerated and could improve cardiac
function. OBJECTIVE:: The objective of this study was to evaluate the hemodynamic
effects of rhBNP in AMI patients revascularized by emergency percutaneous
coronary intervention (PCI) who developed cardiogenic shock. METHODS:: A total of
48 patients with acute ST segment elevation myocardial infarction (STEMI)
complicated by cardiogenic shock and whose hemodynamic status was improved
following emergency PCI were enrolled. Patients were randomly assigned to rhBNP
(n=25) and control (n=23) groups. In addition to standard therapy, study group
individuals received rhBNP by continuous infusion at 0.005 ug kg-1 min-1 for 72
hours. RESULTS:: Baseline characteristics, medications, and peak of cardiac
troponin I (cTnI) were similar between both groups. rhBNP treatment resulted in
consistently improved pulmonary capillary wedge pressure (PCWP) compared to the
control group. Respectively, 7 and 9 patients died in experimental and control
groups. No drug-related serious adverse events occurred in either group.
CONCLUSION:: When added to standard care in stable patients with cardiogenic
shock complicating anterior STEMI, low dose rhBNP improves PCWP and is well
tolerated.
PMID- 28492792
TI - Cervical Cannulation for Surgical Repair of Congenital Cardiac Defects in Infants
and Small Children.
AB - INTRODUCTION:: The biggest challenge faced in minimally invasive pediatric
cardiac surgery is cannulation for cardiopulmonary bypass. Our technique and
experience of cervical cannulation in infants and small children for repair of
congenital cardiac defects is reported in this study. METHODS:: From January 2013
to June 2015, 37 children (22 males) with mean age of 17.97+/-8.63 months and
weight of 8.06+/-1.59 kg were operated on for congenital cardiac defects through
right lateral thoracotomy. The most common diagnosis was ventricular septal
defect (18 patients). In all patients, right common carotid artery, right
internal jugular vein and inferior vena cava were cannulated for institution of
cardiopulmonary bypass and aorta was cross clamped through right 2nd intercostal
space. RESULTS:: There were no deaths or any major complications related to
cervical cannulation. Common carotid artery cannulation provided adequate
arterial inflow while internal jugular vein with inferior vena cava provided
adequate venous return in all patients. No patient required conversion to
sternotomy or developed vascular, neurological or wound related complications.
Three patients had residual lesions (small leak across ventricular septal defect
patch-2, Grade II left atrio-ventricular valve regurgitation-1) and one patient
had mild left ventricular dysfunction. At discharge, both common carotid artery
and internal jugular vein were patent on color Doppler ultrasonography in all
patients. In a mean follow-up period of 11.4+/-2.85 months, all patients were
doing well. No patient had any wound related, neurological or vascular
complication. No patient had residual leak across ventricular septal defect
patch. CONCLUSION:: Cervical cannulation of common carotid artery and internal
jugular vein is a safe, reliable, efficient and quick method for institution of
cardiopulmonary bypass in minimally invasive pediatric cardiac surgery.
PMID- 28492793
TI - Left Atrial Ganglionated Plexi Detection is Related to Heart Rate and Early
Recurrence of Atrial Fibrillation after Surgical Ablation.
AB - INTRODUCTION:: Left atrial ganglionated plexi ablation is an adjuvant technique
used to increase the success rate of surgical ablation of atrial fibrillation.
Ganglionated plexi ablation requires previous detection. We aimed to assess
determinants of successful ganglionated plexi detection and to correlate range of
ganglionated plexi ablation with risk of early atrial fibrillation recurrence.
METHODS:: The study involved 34 consecutive patients referred for surgical
coronary revascularization with concomitant atrial fibrillation ablation.
Ganglionated plexi detection was done by inducing vagal reflexes in the area of
the pulmonary veins and left atrial fat pads. RESULTS:: Detection of GP was
successful in 85% of the patients. There was no difference in preoperative
characteristics nor in atrial fibrillation type between patients in whom
ganglionated plexi detection was successful and others. The number of detected
ganglionated plexi correlated significantly only with preoperative resting heart
rate. Significant negative correlation was found in patients with preoperative
heart rate>75 beat/min in terms of total number of detected ganglionated plexi
(P=0.04). Average number of detected ganglionated plexi was significantly higher
in patients with in-hospital atrial fibrillation recurrence requiring electrical
cardioversion (3.8+/-3) in comparison to rest of the study population (2+/-1.3;
P=0.02). In patients in whom 4 or more ganglionated plexi were detected,
significantly increased risk of in-hospital atrial fibrillation recurrence was
observed (OR 15; 95% CI 1.5-164; P=0.003). CONCLUSION:: Left atrial ganglionated
plexi detection was unsuccessful in a considerable percentage of patients.
Preoperative heart rate significantly influenced positive ganglionated plexi
detection and number of ablated ganglia. Higher number of detected ganglionated
plexi was related with early recurrence of atrial fibrillation.
PMID- 28492795
TI - Anterior Spinal Artery Syndrome Following Coronary Artery Bypass Grafting: a Case
Report.
AB - We present a patient with unstable angina candidate for coronary artery bypass
grafting. Saphenous vein graft was used in obtuse marginal and left internal
mammary artery to left anterior descending artery properly. After surgery, the
patient experienced flaccid paralysis of lower limb and impaired sensation of
touch and warmth of knee and below. A computed tomography angiogram of lower
limbs and thoracolumbar magnetic resonance imaging showed no abnormality. Based
on the symptom, clinical diagnosis of anterior spinal artery syndrome was
considered. The artery of Adamkiewicz is an important supplier to the anterior
spinal artery. Internal thoracic mammary artery, used in coronary artery bypass
grafting, is suspected as a collateral supplier of the artery of Adamkiewicz and
has been accused for cause of spinal infarction.
PMID- 28492794
TI - Exploring Vascular Function Biomarkers: Implications for Rehabilitation.
AB - The endothelium plays an important role in maintaining vascular homeostasis and
regulating blood vessel function. Endothelial function is considered an
independent predictor for risk of future cardiovascular events in cardiovascular
and non-cardiovascular patients, as well as a predictor for postoperative
complications in cardiovascular surgery patients. Brachial artery flow-mediated
dilation by high-resolution ultrasound is widely used to evaluate endothelium
dependent vasodilation, which is mainly mediated by nitric oxide release.
Physical exercise exerts beneficial effects on endothelial function and can be
used in both primary and secondary prevention of cardiac and peripheral artery
diseases, even in the postoperative period of cardiovascular surgery.
PMID- 28492796
TI - A Concomitant Intramyocardial and Pulmonary Hydatid Cyst: A Rare Case Report.
AB - Cardiac hydatid cyst is an uncommon but potentially fatal disease. In cystic
Echinococcus humans are an accidental host. Liver and lungs are the most
frequently involved organs. Herein a unique case of intramyocardial hydatid cyst
of left ventricle along with pulmonary hydatid cyst in a 38-year-old lady is
reported. Surgical removal of the cardiac hydatid cyst was done with the aid of
cardiopulmonary bypass followed by removal of pulmonary hydatid cyst.
PMID- 28492797
TI - Let's Talk about Moving: The Impact of Cardiorespiratory Fitness, Exercise, Steps
and Sitting on Cardiovascular Risk.
PMID- 28492798
TI - Medicinal plants profile used by the 3rd District population of Maceio-AL.
AB - Herein the use of medicinal plants by the population of the 3rd Sanitary District
of Maceio-AL city is reported. Transversal description was conducted from
February 2013 to January 2014, with a sample of 116 individuals of both Gender
Genders aged over 18 years. The ethnobotanical information interviews
ethnobotanical information were obtained through semi - structured questionnaire
featuring the use of medicinal plants and social and economical data. Descriptive
statistics was applied for quantitative variables as mean and standard deviation
and proportions for qualitative variables in the frequency table format. The
results showed that 85.34% of the interviewees used plants for medicinal
purposes. As the majority of these were (73.28%) females in the age group between
30-60 years of old. Among a total of 45 identified plant species, the highest use
frequency were for Boldus Peumus (bilberry), Melissa officinalis (lemon balm),
and Mentha piperita (mint). The most widely used plant foliage part was (53.53%)
prepared as an infusion (55.5%). The use of medicinal plants in Maceio cityis
widespread, highlighting the importance of ethnobotanical knowledge for the study
of medicinal plants.
PMID- 28492799
TI - Reproductive biology of endemic Solanum melissarum Bohs (Solanaceae) and updating
of its current geographic distribution as the basis for its conservation in the
Brazilian Cerrado.
AB - The genus Solanum (family Solanaceae) includes more than 1400 species and has
buzz-pollinated flowers with poricidal anthers. The present study aimed to
describe the distribution, breeding system and pollination mechanism of Solanum
melissarum, a species endemic to Brazil. The study of breeding system was
conducted in an urban forest fragment in Jatai, GO. Distribution data were
gathered from floristic surveys and digital plant databases. The floral
morphology and the pollination mechanism were studied on through field
observations and preserved flowers. The breeding system was determined through
hand pollination treatments. The species has a distribution only in the Brazilian
Atlantic forest coastal, and this study provides the first records of S.
melissarum for the state of Goias. The pendulous flowers have poricidal anthers
close to the stigma, with membranous thecae joined by a connective bearing
osmophores that attract males of Euglossa cordata bees. As they collect
fragrances, the bees press the thecae and pollen is released through a bellows
mechanism. Based on the hand-pollination treatments, this species is self
incompatible. Isolated forest fragments may not include enough pollinators to
ensure the pollination of plants with specialized systems. However, they are
essential for the conservation of species with interesting phytogeographic
patterns, such as the vicariance observed in S. melissarum, and for the
conservation of regional diversity.
PMID- 28492800
TI - Fungal infection control by garlic extracts (Allium sativum L.) and modulation of
peritoneal macrophages activity in murine model of sporotrichosis.
AB - Garlic (Allium sativum L.) is grown all over the world as seasoning and medicinal
vegetable since 3,000 BC. Allicin is the main component of garlic, being
attributed to it the most of its biological activities, such as bactericidal,
antifungal and antiviral actions. However, other compounds of garlic present
antioxidant, hypocholesterolemic, vasodilator activities, protective action
against different types of cancer, and immunomodulatory. Fungal infections are
important causes of morbidity and mortality in people mainly in immunosuppressed
ones. Sporothrix schenckii, the causing agent of Sporotrichosis (most common
subcutaneous mycosis in Latin America), is dimorphic fungus, of saprophytic life
in soil or plants, infecting people and animals mainly through skin injuries and
bruises. The main of this work was to evaluate the influence of garlic consuming
on immune modulation of healthy and infected Swiss mice in induced way by S.
schenckii, since these animals functioning of peritoneal macrophages as well as
the nitric oxide and cytokines' production (IL-1beta, IL-10 and IL-12) and to
evaluate the antifungal potential of garlic with S. schenckii through minimum
inhibitory concentration test and colony-forming units. The results showed that
garlic offers antifungal potential with S. schenckii. The oral taking of garlic
extracts influences the releasing of cytokines by macrophages, regular consuming
shows anti-inflammatory effect, and its acute use may take to an inflammatory
response. Mice that consumed garlic responded more effectively to fight against
the infection.
PMID- 28492801
TI - Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in
breast cancer.
AB - OBJECTIVES: Calcitriol antiproliferative effects were observed in xenografts of
breast cancer cell lines, however they were not yet investigated in tumorgrafts,
consisting of freshly collected breast cancer samples xenografted into animals.
To establish a tumorgraft model, from freshly collected breast cancer samples,
which were directly implanted in nude mice, to study calcitriol effects. METHODS:
Breast cancer samples collected from 12 patients were orthotopically implanted
into nude mice. Animals were treated with weekly intratumoral injections of
calcitriol 3 MUg/Kg, which was previously shown to induce peak serum calcitriol
levels in the predicted therapeutic range. RESULTS: Success engraftment rate was
25%. Tumorgrafts were established from aggressive (HER2 positive or histological
grade 3) highly proliferative samples and original tumor characteristics were
preserved. Calcitriol highly induced its target gene, CYP24A1, indicating that
the genomic vitamin D pathway is active in tumorgrafts. However, no differences
in the expression of proliferation and apoptosis markers (BrdU incorporation,
Ki67, CDKN1A, CDKN1B, BCL2 expression) were observed in these highly
proliferative tumor samples. CONCLUSIONS: Tumorgrafts seem a promising model to
explore other calcitriol doses and regimens, considering the heterogeneity of the
disease and microenvironment interactions.
PMID- 28492802
TI - Gonadotrophic, prolactin, corticosterone, and gonadal hormones levels over 15
months in Giant Amazon River Turtles - Podocnemis expansa (Schweigger, 1812)
(Testudines: Podocnemididae), in captive conditions.
AB - In order to achieve successful captive breeding the Podocnemis expansa, it is
necessary to study their reproductive endocrinology. The purpose of this research
was to evaluate and characterize plasma concentrations in gonadotrophic, gonadic,
corticosterone and prolactin hormones from Giant Amazon Turtles under captive
conditions. Blood samples were collected over a 15 month period. The samples were
assayed by the use of radioimmunoassay, prolactin, corticosterone, LH, FSH,
testosterone, 17beta-estradiol and progesterone. We verified significant seasonal
pattern increase in 17beta-estradiol levels and decrease in progesterone levels
in the course of a year, which indicates vitellogenesis. This is related to
normal ovarian cycles and possibly to the functional integrity of the
hypothalamus-pituitary-gonad axis of captive females. There were negative
correlations between testosterone and corticosterone in the male samples,
suggestive of stress (management stress) on the reproductive system. The plasma
concentrations of gonadotrophic, gonadic, prolactin and corticosterone hormones
may be used as a reference for further research and possible therapeutic
approaches. The data collected during this research are unprecedented for this
species and may serve as a reference for future research regarding the
reproductive cycle of this turtle, also allowing reproductive management while in
captivity. Information about these hormones must be gathered from wild
populations during different periods of the year for better clarification of the
reproductive physiology of this species.
PMID- 28492803
TI - Tropical forages: morphoanatomy of plants grown in areas with the death of
pasture syndrome.
AB - Roots and leaves of Panicum maximum Tanzania, Mombaca and Massai; Urochloa
brizantha Piata, Marandu and Xaraes; Urochloa humidicola Llanero; Urochloa
ruziziensis Ruzizienses; Urochloa hybrida Mulato II and Cynodon nlemfuensis
Estrela-roxa were analyzed, seeking to identify characters for better adaptation
to the environment that may interfere with digestibility of tissue from the point
of view of the rumen in cattle. Were planted ten cultivars in a completely
randomized blocks with three repetitions. Was collected vegetative material,
which histological slides were prepared from middle third of the sections of
roots and leaves. Were observed differences (p>0.05) in the roots: higher volume
of epidermal cells (28.62 um) and overall diameter (1926.41 um) of Llanero;
thicker vascular cylinder (975.09 um) and more protoxylem (42.25) in Estrela-roxa
and occurrence of aerenchyma in cultivars Piata, Mulato II, Xaraes, Massai,
Llanero and Estrela-roxa; Were found higher proportions of bulliform cells in the
leaves (121.07 um) and thicker leaf mesophyll in U. humidicola Llanero (263.63
um); higher proportion of sclerenchyma fibers in Xaraes and Marandu; lower
results for amount of fibers in P. maximum Massai. We conclude that the cultivars
Estrela-roxa, Llanero and Massai have greater adaptability to the environment and
better nutritional quality.
PMID- 28492804
TI - Post-fire reproduction of herbs at a savanna-gallery forest boundary in Distrito
Federal, Brazil.
AB - In Cerrado, studies of post-fire vegetation recovery show that some herbaceous
species are able to flower shortly after fires. However, these were mainly short
term studies that focused on grasslands and savannas. Little is known about the
effects of fire on ground layer of forests that border the savannas in Central
Brazil. Thus, an accidental burning gave us the opportunity to describe the
reproductive activity of the ground layer vegetation after a fire event along a
savanna-forest boundary at the IBGE Ecological Reserve, Brasilia, Brazil. During
the 16-month of the inventory, we registered 170 herbaceous species flowering or
fruiting, of which 52 species (31%) may have been influenced by fire that changed
their times of reproduction. In the savanna plots reproduction peaked at the end
of the rainy season. Of the total number of reproducing species, 90 species
occurred only in the savanna and four in the forest. Five herbs were recorded in
the forest, savanna and border environments. Late dry season fire probably lead
the majority of herbaceous species to have their reproduction spread throughout
the study time.
PMID- 28492806
TI - Plankton crustaceans in bays with different trophic status in Llanquihue lake (41
degrees S Chile).
AB - The Llanquihue lake is included in the called Araucanian or Nord Patagonian lakes
located between 38-41 degrees S. These lakes are characterized by their oligo
mesotrophic status due to human intervention which takes to the increase in
nutrients inputs from industries and towns. Effects on zooplankton assemblages
are observed with marked increase of daphnids abundance. The aim of the present
study is to analyze the trophic status and zooplankton relative abundance in
different bays of Llanquihue lake. It was found direct associations between
chlorophyll a with daphnids percentage, total dissolved nitrogen with reactive
soluble phosphorus nitrogen/phosphorus molar radio with cyclopoids percentage,
and an inverse relation between daphnids and calanoids percentages. The
occurrence of three kinds of microcrustacean assemblages and environmental
conditions was evidenced: the first one with high calanoids percentage, low
species number and low chlorophyll and nutrients concentration, a second with
moderate chlorophyll and nutrients concentration and moderate daphnids
percentage; high species number and a third site with high chlorophyll and
nutrients concentration, high daphnids percentage and high species number.
Daphnids increase under mesotrophic status, agree with similar results observed
for southern Argentinean and New Zealand lakes.
PMID- 28492807
TI - Biochemical parameters of silver catfish (Rhamdia quelen) after transport with
eugenol or essential oil of Lippia alba added to the water.
AB - The transport of live fish is a routine practice in aquaculture and constitutes a
considerable source of stress to the animals. The addition of anesthetic to the
water used for fish transport can prevent or mitigate the deleterious effects of
transport stress. This study investigated the effects of the addition of eugenol
(EUG) (1.5 or 3.0 uL L-1) and essential oil of Lippia alba (EOL) (10 or 20 uL L
1) on metabolic parameters (glycogen, lactate and total protein levels) in liver
and muscle, acetylcholinesterase activity (AChE) in muscle and brain, and the
levels of protein carbonyl (PC), thiobarbituric acid reactive substances (TBARS)
and nonprotein thiol groups (NPSH) and activity of glutathione-S-transferase in
the liver of silver catfish (Rhamdia quelen; Quoy and Gaimard, 1824) transported
for four hours in plastic bags (loading density of 169.2 g L-1). The addition of
various concentrations of EUG (1.5 or 3.0 uL L-1) and EOL (10 or 20 uL L-1) to
the transport water is advisable for the transportation of silver catfish, since
both concentrations of these substances increased the levels of NPSH antioxidant
and decreased the TBARS levels in the liver. In addition, the lower liver levels
of glycogen and lactate in these groups and lower AChE activity in the brain (EOL
10 or 20 uL L-1) compared to the control group indicate that the energetic
metabolism and neurotransmission were lower after administration of anesthetics,
contributing to the maintenance of homeostasis and sedation status.
PMID- 28492808
TI - FAMLF is a target of miR-181b in Burkitt lymphoma.
AB - Burkitt lymphoma (BL) is a highly malignant non-Hodgkin's lymphoma that is
closely related to the abnormal expression of genes. Familial acute myelogenous
leukemia related factor (FAMLF; GenBank accession No. EF413001.1) is a novel gene
that was cloned by our research group, and miR-181b is located in the intron of
the FAMLF gene. To verify the role of miR-181b and FAMLF in BL, RNAhybrid
software was used to predict target site of miR-181b on FAMLF and real-time
quantitative PCR (RQ-PCR) was used to detect expression of miR-181b and FAMLF in
BL patients, Raji cells and unaffected individuals. miR-181b was then transfected
into Raji and CA46 cell lines and FAMLF expression was examined by RQ-PCR and
western blotting. Further, Raji cells viability and proliferation were detected
by MTT and clone formation, and Raji cell cycle and apoptosis were detected by
flow cytometry. The results showed that miR-181b can bind to bases 21-42 of the
FAMLF 5' untranslated region (UTR), FAMLF was highly expressed and miR-181b was
lowly expressed in BL patients compared with unaffected individuals. FAMLF
expression was significantly and inversely correlated to miR-181b expression, and
miR-181b negatively regulated FAMLF at posttranscriptional and translational
levels. A dual-luciferase reporter gene assay identified that the 5' UTR of FAMLF
mRNA contained putative binding sites for miR-181b. Down-regulation of FAMLF by
miR-181b arrested cell cycle, inhibited cell viability and proliferation in a BL
cell line model. Our findings explain a new mechanism of BL pathogenesis and may
also have implications in the therapy of FAMLF-overexpressing BL.
PMID- 28492811
TI - Permanent education in primary health care: perception of local health managers.
AB - Objectives: To know the health education strategies advocated and developed for
workers of primary care, in the view of managers. Method: The study is
characterized as a qualitative, descriptive and exploratory research. A
semistructured interview was used to collect data. The sample population was
chosen intentionally, with an audience of 26 municipal health managers ascribed
to a regional health coordination office, located in the north/northwest of the
Rio Grande do Sul State. Results: The thematic analysis allowed the construction
of two empirical categories: educational strategies, compartmentalized,
discontinuous and with technicist bases; and the insipience/absence of
educational proposals. Final considerations: The results show a reality that
needs to be transformed by all people involved in health work process: teachers
and students, users, members of health councils, workers and managers.
Realistically, there is a quest for change in services, to qualify the
comprehensiveness of health care.
PMID- 28492810
TI - Rimonabant improves metabolic parameters partially attributed to restoration of
high voltage-activated Ca2+ channels in skeletal muscle in HFD-fed mice.
AB - Cannabinoid type 1 receptor (CB1R) inhibition tends to be one of the promising
strategies for the treatment of obesity and other related metabolic disorders.
Although CB1R inhibition may cause adverse psychiatric effects including
depression and anxiety, the investigation of the role of peripheral CB1R on
weight loss and related metabolic parameters are urgently needed. We first
explored the effect of rimonabant, a selective CB1R antagonist/inverse agonist,
on some metabolic parameters in high fat-diet (HFD)-induced obesity in mice.
Then, real-time PCR and electrophysiology were used to explore the contribution
of high voltage-activated Ca2+ channels (HVACCs), especially Cav1.1, on
rimonabant's effect in skeletal muscle (SM) in HFD-induced obesity. Five-week HFD
feeding caused body weight gain, and decreased glucose/insulin tolerance in mice
compared to those in the regular diet group (P<0.05), which was restored by
rimonabant treatment compared to the HFD group (P<0.05). Interestingly, HVACCs
and Cav1.1 were decreased in soleus muscle cells in the HFD group compared to the
control group. Daily treatment with rimonabant for 5 weeks was shown to counter
such decrease (P<0.05). Collectively, our findings provided a novel understanding
for peripheral CB1R's role in the modulation of body weight and glucose
homeostasis and highlight peripheral CB1R as well as Cav1.1 in the SM as
potential targets for obesity treatment.
PMID- 28492809
TI - Serum microRNA-30c levels are correlated with disease progression in Xinjiang
Uygur patients with chronic hepatitis B.
AB - We aimed to investigate the potential role and mechanism of microRNA-30c (miR
30c) in the pathological development of chronic hepatitis B (CHB). The serum
levels of miR-30c in hepatitis B virus (HBV) carrier Xinjiang Uygur patients with
inactive, low-replicative, high-replicative and HBe antigen-positive CHB were
investigated. HepG2 cells were co-transfected with pHBV1.3 and miR-30c mimic or
inhibitor or scramble RNA. The effects of miR-30c dysregulation on HBV
replication and gene expression, cell proliferation and cell cycle were then
investigated. miR-30c was down-regulated in Xinjiang Uygur patients with CHB
compared to healthy controls and its expression level discriminated HBV carrier
patients with inactive, low-replicative, high-replicative and HBe antigen
positive risk for disease progression. Overexpression of miR-30c significantly
inhibited HBV replication and the expressions of HBV pgRNA, capsid-associated
virus DNA and Hbx in hepatoma cells. Moreover, overexpression of miR-30c
significantly inhibited cell proliferation and delayed G1/S phase transition in
hepatoma cells. Opposite effects were obtained after suppression of miR-30c. Our
results indicate that miR-30c was down-regulated in Xinjiang Uygur patients with
CHB, and miR-30c levels could serve as a marker for risk stratification of HBV
infection. Down-regulation of miR-30c may result in the progression of CHB via
promoting HBV replication and cell proliferation.
PMID- 28492812
TI - Palliative care in paediatric oncology in nursing education.
AB - Objective: To identify and understand the view of students regarding palliative
care in paediatric oncology during a graduate programme. Methods: Exploratory
research with a qualitative approach conducted in a school of nursing in Rio de
Janeiro. Data were collected from September to November 2014, through semi
structured interviews with 20 students enrolled in the last period of a graduate
programme. The data were subjected to thematic analysis. Results: The results
produced two thematic units: the (un)preparedness of nursing students regarding
palliative care in paediatric oncology and how the subject of palliative care in
paediatric oncology is approached in the graduate programme. The students
mentioned difficulties in providing this care and their lack of exposure to the
topic during their graduate studies. They stated strategies to prepare for the
provision of care, and talked about how the subject should be addressed in their
curricular programme. Conclusion: It is necessary to expand discussions on
palliative care in paediatric oncology during the nurses' graduate programme.
PMID- 28492813
TI - Patient safety in the care of hospitalised children: evidence for paediatric
nursing.
AB - Objectives: To describe evidence of international literature on the safe care of
the hospitalised child after the World Alliance for Patient Safety and list
contributions of the general theoretical framework of patient safety for
paediatric nursing. Method: An integrative literature review between 2004 and
2015 using the databases PubMed, Cumulative Index of Nursing and Allied Health
Literature (CINAHL), Scopus, Web of Science and Wiley Online Library, and the
descriptors Safety or Patient safety, Hospitalised child, Paediatric nursing, and
Nursing care. Results: Thirty-two articles were analysed, most of which were from
North American, with a descriptive approach. The quality of the recorded
information in the medical records, the use of checklists, and the training of
health workers contribute to safe care in paediatric nursing and improve the
medication process and partnerships with parents. Conclusion: General information
available on patient safety should be incorporated in paediatric nursing care.
PMID- 28492814
TI - Implementation of Rapid Treatment and Interfacility Transport for Patients With
Suspected Stroke by Large-Vessel Occlusion: In One Door and Out the Other.
PMID- 28492815
TI - Enhanced Surgical Recovery Through Enhanced Research From Integrated Health
Systems.
PMID- 28492817
TI - Different Pediatric Survival After Cardiac Arrest-Reply.
PMID- 28492816
TI - Enhanced Recovery After Surgery Program Implementation in 2 Surgical Populations
in an Integrated Health Care Delivery System.
AB - Importance: Novel approaches to perioperative surgical care focus on optimizing
nutrition, mobility, and pain management to minimize adverse events after
surgical procedures. Objective: To evaluate the outcomes of an enhanced recovery
after surgery (ERAS) program among 2 target populations: patients undergoing
elective colorectal resection and patients undergoing emergency hip fracture
repair. Design, Setting, and Participants: A pre-post difference-in-differences
study before and after ERAS implementation in the target populations compared
with contemporaneous surgical comparator groups (patients undergoing elective
gastrointestinal surgery and emergency orthopedic surgery). Implementation began
in February and March 2014 and concluded by the end of 2014 at 20 medical centers
within the Kaiser Permanente Northern California integrated health care delivery
system. Exposures: A multifaceted ERAS program designed with a particular focus
on perioperative pain management, mobility, nutrition, and patient engagement.
Main Outcomes and Measures: The primary outcome was hospital length of stay.
Secondary outcomes included hospital mortality, home discharge, 30-day
readmission rates, and complication rates. Results: The study included a total of
3768 patients undergoing elective colorectal resection (mean [SD] age, 62.7
[14.1] years; 1812 [48.1%] male) and 5002 patients undergoing emergency hip
fracture repair (mean [SD] age, 79.5 [11.8] years; 1586 [31.7%] male). Comparator
surgical patients included 5556 patients undergoing elective gastrointestinal
surgery and 1523 patients undergoing emergency orthopedic surgery. Most process
metrics had significantly greater changes in the ERAS target populations after
implementation compared with comparator surgical populations, including those for
ambulation, nutrition, and opioid use. Hospital length of stay and postoperative
complication rates were also significantly lower among ERAS target populations
after implementation. The rate ratios for postoperative complications were 0.68
(95% CI, 0.46-0.99; P = .04) for patients undergoing colorectal resection and
0.67 (95% CI, 0.45-0.99, P = .05) for patients with hip fracture. Among patients
undergoing colorectal resection, ERAS implementation was associated with
decreased rates of hospital mortality (0.17; 95% CI, 0.03-0.86; P = .03), whereas
among patients with hip fracture, implementation was associated with increased
rates of home discharge (1.24; 95% CI, 1.06-1.44; P = .007). Conclusions and
Relevance: Multicenter implementation of an ERAS program among patients
undergoing elective colorectal resection and patients undergoing emergency hip
fracture repair successfully altered processes of care and was associated with
significant absolute and relative decreases in hospital length of stay and
postoperative complication rates. Rapid, large-scale implementation of a
multidisciplinary ERAS program is feasible and effective in improving surgical
outcomes.
PMID- 28492819
TI - Inappropriate Comparator Group in Study of Selective Serotonin Reuptake
Inhibitors and Risk for Intracranial Hemorrhage.
PMID- 28492818
TI - Different Pediatric Survival After Cardiac Arrest.
PMID- 28492820
TI - Missing Reference.
PMID- 28492821
TI - Risk Associated With Complications and Mortality After Urgent Surgery vs Elective
and Emergency Surgery: Implications for Defining "Quality" and Reporting Outcomes
for Urgent Surgery.
AB - Importance: Given the current climate of outcomes-driven quality reporting, it is
critical to appropriately risk stratify patients using standardized metrics.
Objective: To elucidate the risk associated with urgent surgery on complications
and mortality after general surgical procedures. Design, Setting, and
Participants: This retrospective review used the American College of Surgeons
National Surgery Quality Improvement Program database to capture all general
surgery cases performed at 435 hospitals nationwide between January 1, 2013, and
December 31, 2013. Data analysis was performed from November 11, 2015, to
February 16, 2017. Exposures: Any operations coded as both nonelective and
nonemergency were designated into a novel category titled urgent. Main Outcomes
and Measures: The primary outcome was 30-day mortality; secondary outcomes
included 30-day rates of complications, reoperation, and readmission in urgent
cases compared with both elective and emergency cases. Results: Of 173 643
patients undergoing general surgery (101 632 females and 72 011 males), 130 235
(75.0%) were categorized as elective, 22 592 (13.0%) as emergency, and 20 816
(12.0%) as nonelective and nonemergency. When controlling for standard American
College of Surgeons National Surgery Quality Improvement Program preoperative
risk factors, with elective surgery as the reference value, the 3 groups had
significantly distinct odds ratios (ORs) of experiencing any complication (urgent
surgery: OR, 1.38; 95% CI, 1.30-1.45; P < .001; and emergency surgery: OR, 1.65;
95% CI, 1.55-1.76; P < .001) and of mortality (urgent surgery: OR, 2.32; 95% CI,
2.00-2.68; P < .001; and emergency surgery: OR, 2.91; 95% CI, 2.48-3.41; P <
.001). Surgical procedures performed urgently had a 12.3% rate of morbidity (n =
2560) and a 2.3% rate of mortality (n = 471). Conclusions and Relevance: This
study highlights the need for improved risk stratification on the basis of
urgency because operations performed urgently have distinct rates of morbidity
and mortality compared with procedures performed either electively or emergently.
Because we tie quality outcomes to reimbursement, such a category should improve
predictive models and more accurately reflect the quality and value of care
provided by surgeons who do not have traditional elective practices.
PMID- 28492822
TI - Comparing Anti-Vascular Endothelial Growth Factor Therapies for Central Retinal
Vein Occlusion.
PMID- 28492823
TI - Assessment of the Focused Practice Improvement Module Pilot Program of the
American Board of Dermatology for Meeting Requirements of Maintenance of
Certification.
PMID- 28492825
TI - Mohs Micrographic Surgery Use in the United States Based on Medicare Data.
PMID- 28492824
TI - Perceived Discrimination Experienced by Physician Mothers and Desired Workplace
Changes: A Cross-sectional Survey.
PMID- 28492826
TI - Association of Cost Sharing With Use of Home Health Services Among Medicare
Advantage Enrollees.
AB - Importance: Several policy proposals advocate introducing copayments for home
health care in the Medicare program. To our knowledge, no prior studies have
assessed this cost-containment strategy. Objective: To determine the association
of home health copayments with use of home health services. Design, Setting, and
Participants: A difference-in-differences case-control study of 18 Medicare
Advantage (MA) plans that introduced copayments for home health care between 2007
and 2011 and 18 concurrent control MA plans. The study included 135 302 enrollees
in plans that introduced copayment and 155 892 enrollees in matched control
plans. Exposures: Introduction of copayments for home health care between 2007
and 2011. Main Outcomes and Measures: Proportion of enrollees receiving home
health care, annual numbers of home health episodes, and days receiving home
health care. Results: Copayments for home health visits ranged from $5 to $20 per
visit, which were estimated to be associated with $165 (interquartile range
[IQR], $45-$180) to $660 (IQR, $180-$720) in out-of-pocket spending for the
average user of home health care. The increased copayment for home health care
was not associated with the proportion of enrollees receiving home health care
(adjusted difference-in-differences, -0.15 percentage points; 95% CI, -0.38 to
0.09), the number of home health episodes per user (adjusted difference-in
differences, 0.01; 95% CI, -0.01 to 0.03), and home health days per user
(adjusted difference-in-differences, -0.19; 95% CI, -3.02 to 2.64). In both
intervention and control plans and across all levels of copayments, we observed
higher disenrollment rates among enrollees with greater baseline use of home
health care. Conclusions and Relevance: We found no evidence that imposing
copayments reduced the use of home health services among older adults. More
intensive use of home health services was associated with increased rates of
disenrollment in MA plans. The findings raise questions about the potential
effectiveness of this cost-containment strategy.
PMID- 28492828
TI - Cost Sharing and Home Health Care.
PMID- 28492827
TI - Mother's Day for Women in Medicine-Better Than Roses.
PMID- 28492831
TI - Abrupt Onset of Pustules in a Child.
PMID- 28492829
TI - Inequalities in Life Expectancy Among US Counties, 1980 to 2014: Temporal Trends
and Key Drivers.
AB - Importance: Examining life expectancy by county allows for tracking geographic
disparities over time and assessing factors related to these disparities. This
information is potentially useful for policy makers, clinicians, and researchers
seeking to reduce disparities and increase longevity. Objective: To estimate
annual life tables by county from 1980 to 2014; describe trends in geographic
inequalities in life expectancy and age-specific risk of death; and assess the
proportion of variation in life expectancy explained by variation in
socioeconomic and race/ethnicity factors, behavioral and metabolic risk factors,
and health care factors. Design, Setting, and Participants: Annual county-level
life tables were constructed using small area estimation methods from
deidentified death records from the National Center for Health Statistics (NCHS),
and population counts from the US Census Bureau, NCHS, and the Human Mortality
Database. Measures of geographic inequality in life expectancy and age-specific
mortality risk were calculated. Principal component analysis and ordinary least
squares regression were used to examine the county-level association between life
expectancy and socioeconomic and race/ethnicity factors, behavioral and metabolic
risk factors, and health care factors. Exposures: County of residence. Main
Outcomes and Measures: Life expectancy at birth and age-specific mortality risk.
Results: Counties were combined as needed to create stable units of analysis over
the period 1980 to 2014, reducing the number of areas analyzed from 3142 to 3110.
In 2014, life expectancy at birth for both sexes combined was 79.1 (95%
uncertainty interval [UI], 79.0-79.1) years overall, but differed by 20.1 (95%
UI, 19.1-21.3) years between the counties with the lowest and highest life
expectancy. Absolute geographic inequality in life expectancy increased between
1980 and 2014. Over the same period, absolute geographic inequality in the risk
of death decreased among children and adolescents, but increased among older
adults. Socioeconomic and race/ethnicity factors, behavioral and metabolic risk
factors, and health care factors explained 60%, 74%, and 27% of county-level
variation in life expectancy, respectively. Combined, these factors explained 74%
of this variation. Most of the association between socioeconomic and
race/ethnicity factors and life expectancy was mediated through behavioral and
metabolic risk factors. Conclusions and Relevance: Geographic disparities in life
expectancy among US counties are large and increasing. Much of the variation in
life expectancy among counties can be explained by a combination of socioeconomic
and race/ethnicity factors, behavioral and metabolic risk factors, and health
care factors. Policy action targeting socioeconomic factors and behavioral and
metabolic risk factors may help reverse the trend of increasing disparities in
life expectancy in the United States.
PMID- 28492832
TI - Dementia Care, Women's Health, and Gender Equity: The Value of Well-Timed
Caregiver Support.
PMID- 28492830
TI - Changes in Psychosocial Measures After a 6-Week Field Trial.
AB - Purpose: The purpose of this study was to assess the extent to which intervention
with hearing aids, namely, a 6-week hearing aid field trial, can minimize the
psychosocial consequences of hearing loss in adults who have previously not
sought treatment for their hearing loss. Method: Twenty-four adults with mild to
moderate bilateral sensorineural hearing loss, who had never worn hearing aids or
sought help for their hearing loss, participated in this study. Participants were
fitted with receiver-in-canal hearing aids, bilaterally, and wore them for 6
weeks. Participants completed subjective measures of hearing handicap and
attitudes about hearing loss and hearing aids before, during, and after the
hearing aid trial. A control group of age-matched participants followed the same
experimental protocol, except they were not fitted with hearing aids. Results:
Using hearing aids for 6 weeks significantly reduced participants' perceived
stigma of hearing aids, personal distress and inadequacy due to hearing
difficulties, and hearing handicap. Conclusions: A hearing aid trial can have a
positive effect on a person's attitudes toward wearing hearing aids and decrease
hearing handicap.
PMID- 28492833
TI - Treatment of Low Bone Density or Osteoporosis to Prevent Fracture.
PMID- 28492835
TI - Incorrect Description of Patient Compensation in Methods Section.
PMID- 28492837
TI - Topical Mercurials for the Treatment of Pediculosis.
PMID- 28492834
TI - Apoptosis and Vocal Fold Disease: Clinically Relevant Implications of Epithelial
Cell Death.
AB - Purpose: Vocal fold diseases affecting the epithelium have a detrimental impact
on vocal function. This review article provides an overview of apoptosis, the
most commonly studied type of programmed cell death. Because apoptosis can damage
epithelial cells, this article examines the implications of apoptosis on diseases
affecting the vocal fold cover. Method: A review of the extant literature was
performed. We summarized the topics of epithelial tissue properties and apoptotic
cell death, described what is currently understood about apoptosis in the vocal
fold, and proposed several possible explanations for how the role of abnormal
apoptosis during wound healing may be involved in vocal pathology. Results and
Conclusions: Apoptosis plays an important role in maintaining normal epithelial
tissue function. The biological mechanisms responsible for vocal fold diseases of
epithelial origin are only beginning to emerge. This article discusses
speculations to explain the potential role of deficient versus excessive rates of
apoptosis and how disorganized apoptosis may contribute to the development of
common diseases of the vocal folds.
PMID- 28492838
TI - Revisiting the History and Importance of Phototherapy in Dermatology.
PMID- 28492839
TI - Of Wine Stains and Vases-William Allen Sturge's Diverse Legacy.
PMID- 28492840
TI - Al Rhazes and the Beginning of the End of Smallpox.
PMID- 28492841
TI - Skin Disease as Art.
PMID- 28492843
TI - Spoken Language Production in Young Adults: Examining Syntactic Complexity.
AB - Purpose: In this study, we examined syntactic complexity in the spoken language
samples of young adults. Its purpose was to contribute to the expanding knowledge
base in later language development and to begin building a normative database of
language samples that potentially could be used to evaluate young adults with
known or suspected language impairment. Method: Forty adults (mean age = 22
years, 10 months) with typical language development participated in an interview
that consisted of 3 speaking tasks: a general conversation about common, everyday
topics; a narrative retelling task that involved fables; and a question-and
answer, critical-thinking task about the fables. Each speaker's interview was
audio-recorded, transcribed, broken into communication units, coded for main and
subordinate clauses, entered into Systematic Analysis of Language Transcripts
(Miller, Iglesias, & Nockerts, 2004), and analyzed for mean length of
communication unit and clausal density. Results: Both the narrative and critical
thinking tasks elicited significantly greater syntactic complexity than the
conversational task. It was also found that syntactic complexity was
significantly greater during the narrative task than the critical-thinking task.
Conclusion: Syntactic complexity was best revealed by a narrative task that
involved fables. The study offers benchmarks for language development during
early adulthood.
PMID- 28492844
TI - Antibiotic Overuse: Clinicians Are the Solution.
PMID- 28492845
TI - A Simple, Effective Analogy to Elucidate the Mohs Micrographic Surgery Procedure
The Peanut Butter Cup.
PMID- 28492846
TI - A Large Right Shoulder Mass.
PMID- 28492847
TI - Workplace Factors Associated With Burnout of Family Physicians.
PMID- 28492848
TI - The Role of Vena Cava Filters for Injured Patients: Please Don't Throw the Baby
Out With the Bathwater.
PMID- 28492850
TI - Cancer Screening, Overdiagnosis, and Regulatory Capture.
PMID- 28492849
TI - Language Development and Brain Magnetic Resonance Imaging Characteristics in
Preschool Children With Cerebral Palsy.
AB - Purpose: The purpose of this study was to investigate characteristics of language
development in relation to brain magnetic resonance imaging (MRI) characteristics
and the other contributing factors to language development in children with
cerebral palsy (CP). Method: The study included 172 children with CP who
underwent brain MRI and language assessments between 3 and 7 years of age. The
MRI characteristics were categorized as normal, malformation, periventricular
white matter lesion (PVWL), deep gray matter lesion, focal infarct,
cortical/subcortical lesion, and others. Neurodevelopmental outcomes such as
ambulatory status, manual ability, cognitive function, and accompanying
impairments were assessed. Results: Both receptive and expressive language
development quotients (DQs) were significantly related to PVWL or deep gray
matter lesion severity. In multivariable analysis, only cognitive function was
significantly related to receptive language development, whereas ambulatory
status and cognitive function were significantly associated with expressive
language development. More than one third of the children had a language
developmental discrepancy between receptive and expressive DQs. Children with
cortical/subcortical lesions were at high risk for this discrepancy. Conclusions:
Cognitive function is a key factor for both receptive and expressive language
development. In children with PVWL or deep gray matter lesion, lesion severity
seems to be useful to predict language development.
PMID- 28492851
TI - Colposcopic imaging using visible-light optical coherence tomography.
AB - High-resolution colposcopic optical coherence tomography (OCT) provides key
anatomical measures, such as thickness and minor traumatic injury of vaginal
epithelium, of the female reproductive tract noninvasively. This information can
be helpful in both fundamental investigations in animal models and disease
screenings in humans. We present a fiber-based visible-light OCT and two probe
designs for colposcopic application. One probe conducts circular scanning using a
DC motor, and the other probe is capable of three-dimensional imaging over a 4.6
* 4.6 - mm 2 area using a pair of galvo scanners. Using this colposcopic vis-OCT
with both probes, we acquired high-resolution images from whole isolated macaque
vaginal samples and identified biopsy lesions.
PMID- 28492853
TI - Polarization gating based on Mueller matrices.
AB - We present mathematical formulas generalizing polarization gating (PG)
techniques. PG refers to a collection of imaging methods based on the combination
of different controlled polarization channels. In particular, we show how using
the measured Mueller matrix (MM) of a sample, a widespread number of PG
configurations can be evaluated just from analytical expressions based on the MM
coefficients. We also show the interest of controlling the helicity of the states
of polarization used for PG-based metrology, as this parameter has an impact in
the image contrast of samples. In addition, we highlight the interest of
combining PG techniques with tools of data analysis related to the MM formalism,
such as the well-known MM decompositions. The method discussed in this work is
illustrated with the results of polarimetric measurements done on artificial
phantoms and real ex-vivo tissues.
PMID- 28492852
TI - Characterization and correction of the false-discovery rates in resting state
connectivity using functional near-infrared spectroscopy.
AB - Functional near-infrared spectroscopy (fNIRS) is a noninvasive neuroimaging
technique that uses low levels of red to near-infrared light to measure changes
in cerebral blood oxygenation. Spontaneous (resting state) functional
connectivity (sFC) has become a critical tool for cognitive neuroscience for
understanding task-independent neural networks, revealing pertinent details
differentiating healthy from disordered brain function, and discovering
fluctuations in the synchronization of interacting individuals during
hyperscanning paradigms. Two of the main challenges to sFC-NIRS analysis are (i)
the slow temporal structure of both systemic physiology and the response of blood
vessels, which introduces false spurious correlations, and (ii) motion-related
artifacts that result from movement of the fNIRS sensors on the participants'
head and can introduce non-normal and heavy-tailed noise structures. In this
work, we systematically examine the false-discovery rates of several time- and
frequency-domain metrics of functional connectivity for characterizing sFC-NIRS.
Specifically, we detail the modifications to the statistical models of these
methods needed to avoid high levels of false-discovery related to these two
sources of noise in fNIRS. We compare these analysis procedures using both
simulated and experimental resting-state fNIRS data. Our proposed robust
correlation method has better performance in terms of being more reliable to the
noise outliers due to the motion artifacts.
PMID- 28492854
TI - Evidence of anti-inflammatory effect and percutaneous penetration of a topically
applied fish oil preparation: a photoacoustic spectroscopy study.
AB - This paper investigates the topical anti-inflammatory effect of a fish oil
preparation (FOP) in a croton oil (CO) model of skin inflammation. The
photoacoustic spectroscopy (PAS) was applied to estimate the percutaneous
penetration of the FOP and as a model to evaluate the topical inflammatory
response. After applying CO, the groups of mice received a topical application of
a FOP on the left ear. The right ear received the vehicle that was used to dilute
the CO. After 6 h, ear tissue was collected to determine the percent inhibition
of edema, myeloperoxidase (MPO) activity, and cytokine levels and to perform PAS
measurements. Treatment with FOP reduced edema and MPO activity, which was at
least partially attributed to a decrease in the levels of tumor necrosis factor,
interleukin- 1 ? , interleukin-6, keratinocyte-derived chemokine, and monocyte
chemoattractant protein-1. The topically applied FOP penetrated into the tissue
and decreased the area of the bands that characterize inflamed tissue. The
present results demonstrated the topical anti-inflammatory effect of the FOP. PAS
suggests that FOP anti-inflammatory activity is linked with its ability to
penetrate through the skin.
PMID- 28492855
TI - Incremental Cost-effectiveness of Proliferative Diabetic Retinopathy Treatments:
The Certainty of Uncertainty.
PMID- 28492857
TI - Inappropriate Comparator Group in Study of Selective Serotonin Reuptake
Inhibitors and Risk for Intracranial Hemorrhage-Reply.
PMID- 28492856
TI - Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and
Women: A Clinical Practice Guideline Update From the American College of
Physicians.
AB - Description: This guideline updates the 2008 American College of Physicians (ACP)
recommendations on treatment of low bone density and osteoporosis to prevent
fractures in men and women. This guideline is endorsed by the American Academy of
Family Physicians. Methods: The ACP Clinical Guidelines Committee based these
recommendations on a systematic review of randomized controlled trials;
systematic reviews; large observational studies (for adverse events); and case
reports (for rare events) that were published between 2 January 2005 and 3 June
2011. The review was updated to July 2016 by using a machine-learning method, and
a limited update to October 2016 was done. Clinical outcomes evaluated were
fractures and adverse events. This guideline focuses on the comparative benefits
and risks of short- and long-term pharmacologic treatments for low bone density,
including pharmaceutical prescriptions, calcium, vitamin D, and estrogen.
Evidence was graded according to the GRADE (Grading of Recommendations
Assessment, Development and Evaluation) system. Target Audience and Patient
Population: The target audience for this guideline includes all clinicians. The
target patient population includes men and women with low bone density and
osteoporosis. Recommendation 1: ACP recommends that clinicians offer
pharmacologic treatment with alendronate, risedronate, zoledronic acid, or
denosumab to reduce the risk for hip and vertebral fractures in women who have
known osteoporosis. (Grade: strong recommendation; high-quality evidence).
Recommendation 2: ACP recommends that clinicians treat osteoporotic women with
pharmacologic therapy for 5 years. (Grade: weak recommendation; low-quality
evidence). Recommendation 3: ACP recommends that clinicians offer pharmacologic
treatment with bisphosphonates to reduce the risk for vertebral fracture in men
who have clinically recognized osteoporosis. (Grade: weak recommendation; low
quality evidence). Recommendation 4: ACP recommends against bone density
monitoring during the 5-year pharmacologic treatment period for osteoporosis in
women. (Grade: weak recommendation; low-quality evidence). Recommendation 5: ACP
recommends against using menopausal estrogen therapy or menopausal estrogen plus
progestogen therapy or raloxifene for the treatment of osteoporosis in women.
(Grade: strong recommendation; moderate-quality evidence). Recommendation 6: ACP
recommends that clinicians should make the decision whether to treat osteopenic
women 65 years of age or older who are at a high risk for fracture based on a
discussion of patient preferences, fracture risk profile, and benefits, harms,
and costs of medications. (Grade: weak recommendation; low-quality evidence).
PMID- 28492858
TI - Clinical Practice Guidelines for Osteoporosis: Translating Data to Patients?
PMID- 28492859
TI - Epinephrine Concentrations in EpiPens After the Expiration Date.
PMID- 28492860
TI - Baseline Factors Associated With 6-Month Visual Acuity and Retinal Thickness
Outcomes in Patients With Macular Edema Secondary to Central Retinal Vein
Occlusion or Hemiretinal Vein Occlusion: SCORE2 Study Report 4.
AB - Importance: Macular edema (ME) is the leading cause of decreased visual acuity
(VA) associated with retinal vein occlusion (RVO). Identifying factors associated
with better outcomes in RVO eyes treated with anti-vascular endothelial growth
factor (VEGF) therapy may provide information useful in counseling patients.
Objective: To investigate baseline characteristics associated with 6-month VA and
central subfield thickness (CST) outcomes in participants in the Study of
Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2). Design, Setting,
and Participants: A total of 362 patients with central RVO or hemi-RVO were
enrolled between September 17, 2014, and November 18, 2015, and randomized 1:1 in
a masked fashion to receive bevacizumab or aflibercept. At month 6, 348
participants (96%) had VA outcomes measured and 335 participants (93%) had
spectral domain optical coherence tomography outcomes measured. The current data
analysis was conducted from February 27, 2017, to April 7, 2017. Interventions:
Eyes were randomly assigned to receive an intravitreal injection of bevacizumab,
1.25 mg, or aflibercept, 2.0 mg, at baseline and every 4 weeks, with the primary
outcome measured at 6 months. Main Outcomes and Measures: Change from baseline in
VA letter score (VALS), VALS gain of 15 or more, change from baseline in CST, CST
less than 300 um, and resolution of ME. Baseline factors associated with 6-month
outcome at the 0.05 level in univariate regressions were included in multivariate
regressions, with those significant after multiplicity control by the Hochberg
method reported. Results: The mean (SD) age of patients was 69 (12) years, and
43% were women. Younger patient age (odds ratio [OR], 0.95 per year of age; 95%
CI, 0.93-0.98; P = .007) and lower baseline VALS (OR, 0.96 per letter; 95% CI,
0.94-0.98; P < .001) were associated with a 6-month VALS gain of 15 or greater.
Compared with bevacizumab, aflibercept treatment was associated with a higher
odds of ME resolution (OR, 3.59; 95% CI, 2.22-5.80; P < .001) and CST less than
300 um (OR, 5.30; 95% CI, 2.40-11.67; P = .001), but not with a better VA
outcome. Macular edema was less likely to resolve in eyes that received anti-VEGF
treatment prior to study participation (OR, 0.33; 95% CI, 0.17-0.64; P = .03).
Conclusions and Relevance: In eyes treated with bevacizumab or aflibercept,
younger age and worse baseline VALS were associated with better 6-month VA
outcomes. Aflibercept treatment was associated with more favorable spectral
domain optical coherence tomography outcomes but not VA outcomes. These findings
may be useful in assessing expected response at month 6 after monthly injection
of anti-VEGF agents for treating ME due to CRVO and HRVO. Trial Registration:
clinicaltrials.gov Identifier: NCT01969708.
PMID- 28492861
TI - Vena Cava Filter Use in Trauma and Rates of Pulmonary Embolism, 2003-2015.
AB - Importance: Vena cava filter (VCF) placement for pulmonary embolism (PE)
prophylaxis in trauma is controversial. Limited research exists detailing trends
in VCF use and occurrence of PE over time. Objective: To analyze state and
nationwide temporal trends in VCF placement and PE occurrence from 2003 to 2015
using available data sets. Design, Setting, and Participants: A retrospective
trauma cohort study was conducted using data from the Pennsylvania Trauma Outcome
Study (PTOS) (461 974 patients from 2003 to 2015), the National Trauma Data Bank
(NTDB) (5 755 095 patients from 2003 to 2014), and the National (Nationwide)
Inpatient Sample (NIS) (24 449 476 patients from 2003 to 2013) databases. Main
Outcomes and Measures: Temporal trends in VCF placement and PE rates, filter type
(prophylactic or therapeutic), and established predictors of PE (obesity,
pregnancy, cancer, deep vein thrombosis, major procedure, spinal cord paralysis,
venous injury, lower extremity fracture, pelvic fracture, central line,
intracranial hemorrhage, and blood transfusion). Prophylactic filters were
defined as VCFs placed before or without an existing PE, while therapeutic
filters were defined as VCFs placed after a PE. Results: Of the 461 974 patients
in PTOS, the mean (SD) age was 47.2 (26.4) and 61.6% (284 621) were men; of the 5
755 095 patients in NTDB, the mean age (SD) was 42.0 (24.3) and 63.7% (3 666 504)
were men; and of the 24 449 476 patients in NIS, the mean (SD) age was 58.0
(25.2) and 49.7% (12 160 231) were men. Of patients receiving a filter (11 405 in
the PTOS, 71 029 in the NTDB, and 189 957 in the NIS), most were prophylactic
VCFs (93.6% in the PTOS, 93.5% in the NTDB, and 93.3% in the NIS). Unadjusted and
adjusted temporal trends for the PTOS and NTDB showed initial increases in filter
placement followed by significant declines (unadjusted reductions in VCF
placement rates, 76.8% in the PTOS and 53.3% in the NTDB). The NIS demonstrated a
similar unadjusted trend, with a slight increase and modest decline (22.2%) in
VCF placement rates over time; however, adjusted trends showed a slight but
significant increase in filter rates. Adjusted PE rates for the PTOS and NTDB
showed significant initial increases followed by slight decreases, with limited
variation during the declining filter use periods. The NIS showed an initial
increase in PE rates followed by a period of stagnation. Conclusions and
Relevance: Despite a precipitous decline of VCF use in trauma, PE rates remained
unchanged during this period. Taking this association into consideration, VCFs
may have limited utility in influencing rates of PE. More judicious
identification of at-risk patients is warranted to determine individuals who
would most benefit from a VCF.
PMID- 28492863
TI - Understanding the Emergence of Chronic Posttraumatic Stress Disorder Through
Acute Stress Symptom Networks.
PMID- 28492862
TI - Establishing Baseline Normative Values for the Child Sport Concussion Assessment
Tool.
AB - Importance: The Child Sport Concussion Assessment Tool (SCAT3) is a
postconcussion sideline assessment tool measuring symptoms, cognition, and
balance in preadolescent children. Minimal normative baseline data exist to aid
decision making in clinical and athletic settings. Objective: To collect
normative baseline data for the Child SCAT3 in a large cohort of young athletes.
Design, Setting, and Participants: A cross-sectional study was conducted from May
31 to August 12, 2014, at various sporting events (basketball, soccer, baseball,
and swimming) in Central Wisconsin among children 5 to 13 years of age who were
English-speaking and did not report a lower leg injury within the past 2 months
or a concussion within the past month. Data were analyzed between October 8,
2014, and September 12, 2016. Main Outcomes and Measures: All Child SCAT3
components were assessed: child and parent report of symptom number and severity,
cognition (Standardized Assessment of Concussion-child version [SAC-C]), and
balance (modified Balance Error Scoring System [mBESS] and tandem gait). Summary
statistics, mean differences, and effect sizes were calculated for each test
component. Results: Participants included 478 children (234 girls and 241 boys;
mean [SD] age, 9.9 [1.9] years]) and their parents. Age had the largest effect on
all Child SCAT3 components, with children 5 to 7 years of age reporting higher
mean (SD) symptom severity scores compared with those 11 to 13 years of age (18.2
[10.0] vs 11.3 [9.0]; mean difference, 6.86 [95% CI, 4.22-9.50]; effect size,
0.74) and performing more poorly on the total SAC-C (mean [SD] score, 19.5 [5.1]
vs 26.1 [2.1]; mean difference, -6.59 [95% CI, -7.49 to -5.68]; effect size,
2.1), mBESS (mean [SD] score, 1.67 [1.8] vs 0.76 [1.2]; mean difference, 0.91
[95% CI, 0.53-1.29]; effect size, 0.68), and tandem gait (mean [SD] time, 22.2
[8.3] vs 14.0 [3.7] seconds; mean difference, 8.23 seconds [95% CI, 6.63-9.82];
effect size, 1.55). Sex had a small effect on the mean (SD) number and severity
of symptoms reported by the child (severity: boys, 15.1 [9.8] vs girls, 11.8
[9.2]; mean difference, 3.31 [95% CI, 1.60-5.02]; effect size, 0.35), mean (SD)
number and severity of symptoms reported by the parent (severity: boys, 11.1
[7.7] vs girls, 9.4 [8.1]; mean difference, 1.63 [95% CI, 0.21-3.05]; effect
size, 0.21), mean (SD) total SAC-C score (boys, 23.9 [3.9] vs girls, 24.9 [3.5];
mean difference, -0.92 [95% CI, -1.61 to -0.23]; effect size, -0.25), and mean
(SD) mBESS score (boys, 1.21 [1.5] vs girls, 0.71 [1.0]; mean difference, 0.50
[95% CI, 0.27-0.74]; effect size, 0.38). Conclusions and Relevance: Child SCAT3
baseline normative symptom, cognitive, and balance scores were different, with a
large main effect for age and a small effect for sex. These findings may assist
health care professionals with interpretation of Child SCAT3 scores for young
athletes with a concussion in athletic and clinical settings.
PMID- 28492864
TI - Induction of Immune Reaction in Benign Melanocytic Nevi Without Halo During
Nivolumab Therapy in a Patient With Melanoma.
PMID- 28492866
TI - Response to de Wit et al., 2016, "Characteristics of Auditory Processing
Disorders: A Systematic Review".
AB - Purpose: This letter to the editor is in response to a review by de Wit et al.
(2016), "Characteristics of Auditory Processing Disorders: A Systematic Review,"
published in April 2016 by Journal of Speech, Language, and Hearing Research.
Conclusion: The author argues that the conclusions in the de Wit et al. (2016)
review are unfortunate in light of advances made in the clinical diagnosis and
treatment of bottom-up auditory processing disorders in children.
PMID- 28492867
TI - Distracted Driving With Attention-Deficit/Hyperactivity Disorder.
PMID- 28492865
TI - The Relationship Between Iron Deficiency Anemia and Sensorineural Hearing Loss in
the Pediatric and Adolescent Population.
AB - Purpose: A correlation between iron deficiency anemia (IDA) and sudden
sensorineural hearing loss (SNHL) was described in adults. In this study, we
examined if there is a relationship between IDA and hearing loss in the pediatric
population. Method: This was a retrospective cohort study of data collected from
the Informatics for Integrating Biology and the Bedside database from 2011 to
2016. Children and adolescents 4-21 years old seen at Penn State Milton S.
Hershey Medical Center, Hershey, PA, were examined for hearing loss and IDA
status. Hearing loss was determined by International Classification of Disease-9
and -10 codes, and IDA was determined by both low hemoglobin and serum ferritin
levels for age and sex. Results: We identified 20,113 patients. Prevalence of
hearing loss and IDA was 1.7% and 2.3%, respectively. The prevalence of all
hearing loss was 3.0% in the IDA cohort and 1.7% in those without IDA. Children
and adolescents with IDA are at increased odds of developing SNHL (adjusted odds
ratio: 3.67, 95% CI [1.60-7.30]). Conclusions: Children with IDA demonstrate
increased likelihood of SNHL. Although correction of IDA in those with hearing
loss has yet to be linked to improvements in hearing outcomes, screening for and
correcting IDA among pediatric patients will positively affect overall health
status. : Supplemental Material: https://doi.org/10.23641/asha.5087071.
PMID- 28492869
TI - Effects of Magnification on Emotion Perception in Patients With Age-Related
Macular Degeneration.
AB - Purpose: Individuals with low vision often experience difficulties in performing
tasks of daily living, such as face perception. This leads them to having
difficulties with social interactions, as they can no longer correctly perceive
the emotion of others. The present study investigated the effects of
magnification on face perception in participants with age-related macular
degeneration (AMD), and their ability to detect and categorize emotions. It was
hypothesized that patients with AMD would be less accurate in comparison to
healthy controls, but that magnification would improve their performance to that
of controls. Methods: Faces containing happy, angry, or neutral emotion were both
doubled (equivalent of arm's length distance) and decreased by half in size
(equivalent of across the street). The ability to detect and to discriminate
emotional content was compared between 20 AMD patients and 7 age-matched
controls. Eye movements were recorded while conducting both tasks. Results:
Regardless of stimulus size, when compared to controls, we observed that
individuals with AMD consistently performed with lower accuracy in both emotion
detection and categorization tasks. Moreover, having images undergo a 2-fold
increase in size did improve performance, but did not equate AMD participants'
performance to that of the controls in either the emotion detection or
categorization task. Eye movements in AMD participants were highly variable in
position compared to controls. Conclusions: The data suggest that magnification
alone does not appear to be the answer for improving emotion perception within
individuals with low vision. Next steps should include an evaluation of the
effects of viewing strategy.
PMID- 28492870
TI - Radiologic Parameters of Orbital Bone Remodeling in Thyroid Eye Disease.
AB - Purpose: To radiologically examine for the presence of bony remodeling of the
orbit in thyroid eye disease (TED). Methods: Computed tomography (CT) scans of
248 orbits of 124 patients with TED and 185 orbits of 138 controls were
retrospectively reviewed, and the following parameters measured: the angle of the
inferomedial orbital strut (AIOS), the angle of the medial wall (AMW), and the
diameters of the extraocular muscles. The association of TED with the AIOS or AMW
was analyzed with linear regression models, and the correlations between the AMW
or AIOS measurements with the extraocular muscle measurements were determined.
Results: Overall, the AIOS was found to be larger (P < 0.001) and the AMW smaller
(P = 0.045) in patients with TED compared to controls. After adjusting for age
and sex, the larger AIOS in TED remained significant (P < 0.001), but the smaller
AMW in TED patients was no longer significant (P = 0.07). There was a negative
correlation between AMW and the calculated average cross-sectional area of the
medial rectus in TED (r = -0.23, P = 0.01). Conclusions: A difference in the
structure of the bony orbit in TED compared to controls may be demonstrated by
the AIOS and AMW radiological parameters. This likely represents the presence of
bony remodeling in TED, which may be related to the expansion of the intraorbital
soft tissue volume.
PMID- 28492868
TI - Efficacy of Flecainide in the Treatment of Catecholaminergic Polymorphic
Ventricular Tachycardia: A Randomized Clinical Trial.
AB - Importance: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a
potentially lethal genetic arrhythmia syndrome characterized by polymorphic
ventricular tachycardia with physical or emotional stress, for which current
therapy with beta-blockers is incompletely effective. Flecainide acetate directly
suppresses sarcoplasmic reticulum calcium release-the cellular mechanism
responsible for triggering ventricular arrhythmias in CPVT-but has never been
assessed prospectively. Objective: To determine whether flecainide dosed to
therapeutic levels and added to beta-blocker therapy is superior to beta-blocker
therapy alone for the prevention of exercise-induced arrhythmias in CPVT. Design,
Setting, and Participants: This investigator-initiated, multicenter, single
blind, placebo-controlled crossover clinical trial was conducted from December
19, 2011, through December 29, 2015, with a midtrial protocol change at 10 US
sites. Patients with a clinical diagnosis of CPVT and an implantable cardioverter
defibrillator underwent a baseline exercise test while receiving maximally
tolerated beta-blocker therapy that was continued throughout the trial. Patients
were then randomized to treatment A (flecainide or placebo) for 3 months,
followed by exercise testing. After a 1-week washout period, patients crossed
over to treatment B (placebo or flecainide) for 3 months, followed by exercise
testing. Interventions: Patients received oral flecainide or placebo twice daily,
with the dosage guided by trough serum levels. Main Outcomes and Measures: The
primary end point of ventricular arrhythmias during exercise was compared between
the flecainide and placebo arms. Exercise tests were scored on an ordinal scale
of worst ventricular arrhythmia observed (0 indicates no ectopy; 1, isolated
premature ventricular beats; 2, bigeminy; 3, couplets; and 4, nonsustained
ventricular tachycardia). Results: Of 14 patients (7 males and 7 females; median
age, 16 years [interquartile range, 15.0-22.5 years]) randomized, 13 completed
the study. The median baseline exercise test score was 3.0 (range, 0-4), with no
difference noted between the baseline and placebo (median, 2.5; range, 0-4)
exercise scores. The median ventricular arrhythmia score during exercise was
significantly reduced by flecainide (0 [range, 0-2] vs 2.5 [range, 0-4] for
placebo; P < .01), with complete suppression observed in 11 of 13 patients (85%).
Overall and serious adverse events did not differ between the flecainide and
placebo arms. Conclusions and Relevance: In this randomized clinical trial of
patients with CPVT, flecainide plus beta-blocker significantly reduced
ventricular ectopy during exercise compared with placebo plus beta-blocker and
beta-blocker alone. Trial Registration: clinicaltrials.gov Identifier:
NCT01117454.
PMID- 28492871
TI - Risk Factors for Posterior Subcapsular Cataract in Retinitis Pigmentosa.
AB - Purpose: Posterior subcapsular cataract (PSC) is a frequent complication in
patients with retinitis pigmentosa (RP). The risk factors for PSC formation in RP
are largely unknown. The purpose of this study was to investigate the risk
factors for PSC. Methods: We retrospectively studied a total of 322 eyes of 173
patients who were diagnosed with typical RP. We considered the following possible
risk factors for PSC: age, sex, hypertension, diabetes mellitus, high myopia,
asthma, history of steroid intake, and aqueous flare. Aqueous flare values were
measured consecutively in 2012 and 2013 using a laser flare cell meter. The lens
including PSC was examined with a slit lamp after dilation with tropicamide 1%
and phenylephrine 2.5%. Results: The geometric mean values of aqueous flare and
mean values of visual acuity were significantly higher for the RP patients with
PSC compared to those without PSC (P = 0.0003, P = 0.0004, respectively). When
the aqueous flare values were assessed continuously, each 1-log-transformed
increase in flare levels was associated with an elevation of the likelihood of
having PSC after multivariable adjustment (odds ratio: 1.71; 95% confidence
interval: 1.05-2.77). There were no significant associations of the other
possible risk factors with PSC. Conclusions: Our analysis demonstrated that
elevated aqueous flare is a significant risk factor for PSC formation. This
result might provide insights into the association of inflammation and the
pathogenesis of PSC formation in RP.
PMID- 28492872
TI - Urinary Isoprostane Levels and Age-Related Macular Degeneration.
AB - Purpose: Oxidative stress, characterized by an excessive production of reactive
oxygen intermediates has been suggested to play a role in the pathogenesis of age
related macular degeneration (AMD). We examined the association of urinary F2
isoprostanes (F2-IsoPs), a marker of lipid peroxidation and the most reliable
marker of oxidative damage with AMD. Methods: We included 238 adults with AMD and
390 age- and sex-matched controls without AMD who participated in a population
based cross-sectional study in Singapore (Singapore Chinese Eye Study, 2009
2011). AMD was graded from retinal photographs using the Wisconsin Age-Related
Maculopathy Grading System. Urinary-free F2-IsoPs (pmol/mmol of creatinine) were
measured by gas chromatography mass spectrometry (GC-MS). The association between
F2-IsoPs and AMD was examined using unconditional logistic regression models
adjusted for potential confounders including smoking, body mass index (BMI),
blood pressure, total and high-density lipoprotein cholesterol, and history of
cardiovascular disease. Results: Higher levels of F2-IsoPs were associated with
AMD independent of potential confounders. Compared to quartile 1 (Q1) of F2
IsoPs, the multivariable odds ratio (95% confidence interval) of AMD in quartiles
2, 3, and 4 were 2.05 (1.26-3.32), 1.80 (1.10-2.94), and 1.76 (1.06-2.94),
respectively. In subgroup analyses comparing Q4 to Q1, this association was
stronger in women, those with BMI less than 25 kg/m2 and those with hypertension,
but no significant interaction was found (P interaction > 0.1 for each strata).
Conclusions: Higher levels of urinary F2-IsoPs levels were associated with AMD
independent of potential confounders in Chinese adults.
PMID- 28492873
TI - Sphingosine-1-Phosphate Mediates Fibrosis in Orbital Fibroblasts in Graves'
Orbitopathy.
AB - Purpose: To investigate the effect of sphingosine-1-phosphate (S1P) on fibrosis
in orbital fibroblasts in Graves' orbitopathy (GO). Methods: Orbital fibroblasts
were cultured from orbital adipose/connective tissues of patients with GO and
healthy control subjects. Effects of treatment with TGF-beta and cigarette smoke
extract (CSE) on S1P receptor (S1PR) messenger RNA (mRNA) and S1P expression were
evaluated by real-time polymerase chain reaction and Western blotting. To
evaluate the role of S1P in fibrosis, cells were pretreated with W146 (S1PR1
antagonist); JTE013 (S1PR2 antagonist); FTY720 (S1PR1 modulator); or 5C
(sphingosine kinase-1 blocker) for 1 hour before stimulation with TGF-beta, CSE,
or IL-1beta. Expression of fibrosis-related proteins (collagen Ialpha,
fibronectin, and alpha-smooth muscle actin [SMA]) and tissue remodeling-related
proteins (matrix metalloproteinases [MMPs] and tissue inhibitor of
metalloproteinase [TIMP]-1) was then evaluated by Western blotting. Results:
Expression levels of S1PR mRNA and S1P in GO orbital fibroblasts increased upon
TGF-beta and CSE treatment. Treatment with S1PR blockers and 5C inhibited TGF
beta and CSE-induced expression of collagen Ialpha, fibronectin, and alpha-SMA,
as well as IL-1beta-induced expression of MMP-1, MMP-2, MMP-9, and TIMP-1.
Exogenous S1P treatment without profibrotic stimulants upregulated collagen
Ialpha, fibronectin, alpha-SMA, MMP-1, MMP-2, MMP-9, and TIMP-1 expression in a
dose-dependent manner. Conclusions: Blocking of S1PR activity and inhibition of
S1P synthesis led to decreased expression of fibrosis and tissue remodeling
related proteins in primary cultures of orbital fibroblasts derived from patients
with GO. Thus, modulation of S1P activity might have therapeutic potential in the
suppression of fibrosis in GO.
PMID- 28492875
TI - The USPSTF Recommendation on Thyroid Cancer Screening: Don't "Check Your Neck".
PMID- 28492874
TI - Peripapillary Retinal Pigment Epithelium Layer Shape Changes From Acetazolamide
Treatment in the Idiopathic Intracranial Hypertension Treatment Trial.
AB - Purpose: Recent studies indicate that the amount of deformation of the
peripapillary retinal pigment epithelium and Bruch's membrane (pRPE/BM) toward or
away from the vitreous may reflect acute changes in cerebrospinal fluid pressure.
The study purpose is to determine if changes in optic-nerve-head (ONH) shape
reflect a treatment effect (acetazolamide/placebo + weight management) using the
optical coherence tomography (OCT) substudy of the Idiopathic Intracranial
Hypertension Treatment Trial (IIHTT) at baseline, 3, and 6 months. Methods: The
pRPE/BM shape deformation was quantified and compared with ONH volume,
peripapillary retinal nerve fiber layer (pRNFL), and total retinal (pTR)
thicknesses in the acetazolamide group (39 subjects) and placebo group (31
subjects) at baseline, 3, and 6 months. Results: Mean changes of the pRPE/BM
shape measure were significant and in the positive direction (away from the
vitreous) for the acetazolamide group (P < 0.01), but not for the placebo group.
The three OCT measures reflecting the reduction of optic disc swelling were
significant in both treatment groups but greater in the acetazolamide group (P <
0.01). Conclusions: Change in the pRPE/BM shape away from the vitreous reflects
the effect of acetazolamide + weight management in reducing the pressure
differential between the intraocular and retrobulbar arachnoid space. Weight
management alone was also associated with a decrease in optic nerve volume/edema
but without a significant change in the pRPE/BM shape, implying an alternative
mechanism for improvement in papilledema and axoplasmic flow, independent of a
reduction in the pressure differential. (ClinicalTrials.gov number,
NCT01003639.).
PMID- 28492876
TI - Pulmonary Embolism and Deep Venous Thrombosis in Patients Hospitalized With
Syncope: A Multicenter Cross-sectional Study in Toronto, Ontario, Canada.
PMID- 28492878
TI - Investigation Into Opioid Crisis Targets Drug Companies.
PMID- 28492877
TI - The Center Cannot Hold: Medicine, Music, and the Mind.
PMID- 28492880
TI - Maker of Duodenoscopes Under Scrutiny Again.
PMID- 28492879
TI - Hearing Focuses on Proposed Cuts in Cancer Research.
PMID- 28492881
TI - Incorrect Unit of Measure.
PMID- 28492882
TI - Misspelling of Author Name.
PMID- 28492883
TI - Incorrect Funder.
PMID- 28492884
TI - Introducing "Genomics and Precision Health".
PMID- 28492885
TI - Treatment of KRAS-Mutant Non-Small Cell Lung Cancer: The End of the Beginning for
Targeted Therapies.
PMID- 28492886
TI - How to Look for Thyroid Cancer.
PMID- 28492888
TI - Finding the Rare Pathogenic Variants in a Human Genome.
PMID- 28492889
TI - Medicolegal.
PMID- 28492890
TI - Association Between Long-term Quinine Exposure and All-Cause Mortality.
PMID- 28492891
TI - Use of the qSOFA Score in the Emergency Department.
PMID- 28492892
TI - Outlier in Analysis of Cancer Mortality by US County.
PMID- 28492893
TI - Legal Complexities of Global Vaccine Compensation Systems.
PMID- 28492894
TI - Use of the qSOFA Score in the Emergency Department-Reply.
PMID- 28492895
TI - Outlier in Analysis of Cancer Mortality by US County-Reply.
PMID- 28492896
TI - Legal Complexities of Global Vaccine Compensation Systems-Reply.
PMID- 28492897
TI - Farewell to a Cancer That Never Was.
PMID- 28492898
TI - Selumetinib Plus Docetaxel Compared With Docetaxel Alone and Progression-Free
Survival in Patients With KRAS-Mutant Advanced Non-Small Cell Lung Cancer: The
SELECT-1 Randomized Clinical Trial.
AB - Importance: There are no specifically approved targeted therapies for the most
common genomically defined subset of non-small cell lung cancer (NSCLC), KRAS
mutant lung cancer. Objective: To compare efficacy of the mitogen-activated
protein kinase kinase (MEK) inhibitor selumetinib + docetaxel with docetaxel
alone as a second-line therapy for advanced KRAS-mutant NSCLC. Design, Setting,
and Participants: Multinational, randomized clinical trial conducted at 202 sites
across 25 countries from October 2013 through January 2016. Of 3323 patients with
advanced NSCLC and disease progression following first-line anticancer therapy
tested for a KRAS mutation, 866 were enrolled and 510 randomized. Primary reason
for exclusion was ineligibility. The data cutoff date for analysis was June 7,
2016. Interventions: Patients were randomized 1:1; 254 to receive selumetinib +
docetaxel and 256 to receive placebo + docetaxel. Main Outcomes and Measures:
Primary end point was investigator assessed progression-free survival. Secondary
end points included overall survival, objective response rate, duration of
response, effects on disease-related symptoms, safety, and tolerability. Results:
Of 510 randomized patients (mean age, 61.4 years [SD, 8.3]; women, 207 [41%]),
505 patients (99%) received treatment and completed the study (251 received
selumetinib + docetaxel; 254 received placebo + docetaxel). At the time of data
cutoff, 447 patients (88%) had experienced a progression event and 346 deaths
(68%) had occurred. Median progression-free survival was 3.9 months
(interquartile range [IQR], 1.5-5.9) with selumetinib + docetaxel and 2.8 months
(IQR, 1.4-5.5) with placebo + docetaxel (difference, 1.1 months; hazard ratio
[HR], 0.93 [95% CI, 0.77-1.12]; P = .44). Median overall survival was 8.7 months
(IQR, 3.6-16.8) with selumetinib + docetaxel and 7.9 months (IQR, 3.8-20.1) with
placebo + docetaxel (difference, 0.9 months; HR, 1.05 [95% CI, 0.85-1.30]; P =
.64). Objective response rate was 20.1% with selumetinib + docetaxel and 13.7%
with placebo + docetaxel (difference, 6.4%; odds ratio, 1.61 [95% CI, 1.00-2.62];
P = .05). Median duration of response was 2.9 months (IQR, 1.7-4.8; 95% CI, 2.7
4.1) with selumetinib + docetaxel and 4.5 months (IQR, 2.3-7.3; 95% CI, 2.8-5.6)
with placebo + docetaxel. Adverse events of grade 3 or higher were more frequent
with selumetinib + docetaxel (169 adverse events [67%] for selumetinib +
docetaxel vs 115 adverse events [45%] for placebo + docetaxel; difference, 22%).
Conclusions and Relevance: Among patients with previously treated advanced KRAS
mutant non-small cell lung cancer, addition of selumetinib to docetaxel did not
improve progression-free survival compared with docetaxel alone. Trial
Registration: clinicaltrials.gov: NCT01933932.
PMID- 28492900
TI - JAMA patient page. Screening for Thyroid Cancer.
PMID- 28492899
TI - Postmarket Safety Events Among Novel Therapeutics Approved by the US Food and
Drug Administration Between 2001 and 2010.
AB - Importance: Postmarket safety events of novel pharmaceuticals and biologics occur
when new safety risks are identified after initial regulatory approval of these
therapeutics. These safety events can change how novel therapeutics are used in
clinical practice and inform patient and clinician decision making. Objectives:
To characterize the frequency of postmarket safety events among novel
therapeutics approved by the US Food and Drug Administration (FDA), and to
examine whether any novel therapeutic characteristics known at the time of FDA
approval were associated with increased risk. Design and Setting: Cohort study of
all novel therapeutics approved by the FDA between January 1, 2001, and December
31, 2010, followed up through February 28, 2017. Exposures: Novel therapeutic
characteristics known at the time of FDA approval, including drug class,
therapeutic area, priority review, accelerated approval, orphan status, near
regulatory deadline approval, and regulatory review time. Main Outcomes and
Measures: A composite of (1) withdrawals due to safety concerns, (2) FDA issuance
of incremental boxed warnings added in the postmarket period, and (3) FDA
issuance of safety communications. Results: From 2001 through 2010, the FDA
approved 222 novel therapeutics (183 pharmaceuticals and 39 biologics). There
were 123 new postmarket safety events (3 withdrawals, 61 boxed warnings, and 59
safety communications) during a median follow-up period of 11.7 years
(interquartile range [IQR], 8.7-13.8 years), affecting 71 (32.0%) of the novel
therapeutics. The median time from approval to first postmarket safety event was
4.2 years (IQR, 2.5-6.0 years), and the proportion of novel therapeutics affected
by a postmarket safety event at 10 years was 30.8% (95% CI, 25.1%-37.5%). In
multivariable analysis, postmarket safety events were statistically significantly
more frequent among biologics (incidence rate ratio [IRR] = 1.93; 95% CI, 1.06
3.52; P = .03), therapeutics indicated for the treatment of psychiatric disease
(IRR = 3.78; 95% CI, 1.77-8.06; P < .001), those receiving accelerated approval
(IRR = 2.20; 95% CI, 1.15-4.21; P = .02), and those with near-regulatory deadline
approval (IRR = 1.90; 95% CI, 1.19-3.05; P = .008); events were statistically
significantly less frequent among those with regulatory review times less than
200 days (IRR = 0.46; 95% CI, 0.24-0.87; P = .02). Conclusions and Relevance:
Among 222 novel therapeutics approved by the FDA from 2001 through 2010, 32% were
affected by a postmarket safety event. Biologics, psychiatric therapeutics, and
accelerated and near-regulatory deadline approval were statistically
significantly associated with higher rates of events, highlighting the need for
continuous monitoring of the safety of novel therapeutics throughout their life
cycle.
PMID- 28492902
TI - A piece of my mind: Medical Education and the Minority Tax.
PMID- 28492904
TI - Screening for Thyroid Cancer: Updated Evidence Report and Systematic Review for
the US Preventive Services Task Force.
AB - Importance: The incidence of detected thyroid cancer cases has been increasing in
the United States since 1975. The majority of thyroid cancers are differentiated
cancers with excellent prognosis and long-term survival. Objective: To
systematically review the benefits and harms associated with thyroid cancer
screening and treatment of early thyroid cancer in asymptomatic adults to inform
the US Preventive Services Task Force. Data Sources: Searches of MEDLINE, PubMed,
and the Cochrane Central Register of Controlled Trials for relevant studies
published from January 1966 through January 2016, with active surveillance
through December 2016. Study Selection: English-language studies conducted in
asymptomatic adult populations. Data Extraction and Synthesis: Two reviewers
independently appraised the articles and extracted relevant study data from fair-
or good-quality studies. Random-effects meta-analyses were conducted to pool
surgical harms. Main Outcomes and Measures: Thyroid cancer morbidity and
mortality, test accuracy to detect thyroid nodules or thyroid cancer, and harms
resulting from screening (including overdiagnosis) or treatment of thyroid
cancer. Results: Of 10 424 abstracts, 707 full-text articles were reviewed, and
67 studies were included for this review. No fair- to good-quality studies
directly examined the benefit of thyroid cancer screening. In 2 studies (n =
354), neck palpation was not sensitive to detect thyroid nodules. In 2
methodologically limited studies (n = 243), a combination of selected high-risk
sonographic features was specific for thyroid malignancy. Three studies (n =
5894) directly addressed the harms of thyroid cancer screening, none of which
suggested any serious harms from screening or ultrasound-guided fine-needle
aspiration. No screening studies directly examined the risk of overdiagnosis. Two
observational studies (n = 39 211) included cohorts of persons treated for well
differentiated thyroid cancer and persons with no surgery or surveillance;
however, these studies did not adjust for confounders and therefore were not
designed to determine if earlier or immediate treatment vs delayed or no surgical
treatment improves patient outcomes. Based on 36 studies (n = 43 295), the 95% CI
for the rate of surgical harm was 2.12 to 5.93 cases of permanent
hypoparathyroidism per 100 thyroidectomies and 0.99 to 2.13 cases of recurrent
laryngeal nerve palsy per 100 operations. Based on 16 studies (n = 291 796),
treatment of differentiated thyroid cancer with radioactive iodine is associated
with a small increase in risk of second primary malignancies and with increased
risk of permanent adverse effects on the salivary gland, such as dry mouth.
Conclusions and Relevance: Although ultrasonography of the neck using high-risk
sonographic characteristics plus follow-up cytology from fine-needle aspiration
can identify thyroid cancers, it is unclear if population-based or targeted
screening can decrease mortality rates or improve important patient health
outcomes. Screening that results in the identification of indolent thyroid
cancers, and treatment of these overdiagnosed cancers, may increase the risk of
patient harms.
PMID- 28492906
TI - How Much Do You Drink?
PMID- 28492905
TI - Screening for Thyroid Cancer: US Preventive Services Task Force Recommendation
Statement.
AB - Importance: The incidence of thyroid cancer detection has increased by 4.5% per
year over the last 10 years, faster than for any other cancer, but without a
corresponding change in the mortality rate. In 2013, the incidence rate of
thyroid cancer in the United States was 15.3 cases per 100 000 persons. Most
cases of thyroid cancer have a good prognosis; the 5-year survival rate for
thyroid cancer overall is 98.1%. Objective: To update the US Preventive Services
Task Force (USPSTF) recommendation on screening for thyroid cancer. Evidence
Review: The USPSTF reviewed the evidence on the benefits and harms of screening
for thyroid cancer in asymptomatic adults, the diagnostic accuracy of screening
(including neck palpation and ultrasound), and the benefits and harms of
treatment of screen-detected thyroid cancer. Findings: The USPSTF found
inadequate direct evidence on the benefits of screening but determined that the
magnitude of the overall benefits of screening and treatment can be bounded as no
greater than small, given the relative rarity of thyroid cancer, the apparent
lack of difference in outcomes between patients who are treated vs monitored (for
the most common tumor types), and observational evidence showing no change in
mortality over time after introduction of a mass screening program. The USPSTF
found inadequate direct evidence on the harms of screening but determined that
the overall magnitude of the harms of screening and treatment can be bounded as
at least moderate, given adequate evidence of harms of treatment and indirect
evidence that overdiagnosis and overtreatment are likely to be substantial with
population-based screening. The USPSTF therefore determined that the net benefit
of screening for thyroid cancer is negative. Conclusions and Recommendation: The
USPSTF recommends against screening for thyroid cancer in asymptomatic adults. (D
recommendation).
PMID- 28492908
TI - A Path Beyond Advocacy to Improve Mental Health Services for Children and
Families: Population Health Management.
PMID- 28492907
TI - Medicaid's Impact on Overdose Rates.
PMID- 28492909
TI - The Controversial Epidemiology of Left Ventricular Dysfunction in Patients With
Myotonic Dystrophy Type 1.
PMID- 28492911
TI - How Much Information Do People With Aphasia Convey via Gesture?
AB - Purpose : People with aphasia (PWA) face significant challenges in verbally
expressing their communicative intentions. Different types of gestures are
produced spontaneously by PWA, and a potentially compensatory function of these
gestures has been discussed. The current study aimed to investigate how much
information PWA communicate through 3 types of gesture and the communicative
effectiveness of such gestures. Method: Listeners without language impairment
rated the information content of short video clips taken from PWA in
conversation. Listeners were asked to rate communication within a speech-only
condition and a gesture + speech condition. Results: The results revealed that
the participants' interpretations of the communicative intentions expressed in
the clips of PWA were significantly more accurate in the gesture + speech
condition for all tested gesture types. Conclusion: It was concluded that all 3
gesture types under investigation contributed to the expression of semantic
meaning communicated by PWA. Gestures are an important communicative means for
PWA and should be regarded as such by their interlocutors. Gestures have been
shown to enhance listeners' interpretation of PWA's overall communication.
PMID- 28492910
TI - Effect of Bevacizumab vs Aflibercept on Visual Acuity Among Patients With Macular
Edema Due to Central Retinal Vein Occlusion: The SCORE2 Randomized Clinical
Trial.
AB - Importance: Studies have established the efficacy and safety of aflibercept for
the treatment of macular edema due to central retinal vein occlusion. Bevacizumab
is used off-label to treat this condition despite the absence of supporting data.
Objective: To investigate whether bevacizumab is noninferior to aflibercept for
the treatment of macular edema secondary to central retinal or hemiretinal vein
occlusion. Design, Setting, and Participants: The SCORE2 randomized
noninferiority clinical trial was conducted at 66 private practice or academic
centers in the United States, and included 362 patients with macular edema due to
central retinal or hemiretinal vein occlusion who were randomized 1:1 to receive
aflibercept or bevacizumab. The first participant was randomized on September 17,
2014, and the last month 6 visit occurred on May 6, 2016. Analyses included data
available as of December 30, 2016. Interventions: Eyes were randomized to receive
intravitreal injection of bevacizumab (1.25 mg; n = 182) or aflibercept (2.0 mg;
n = 180) every 4 weeks through month 6. Main Outcomes and Measures: The primary
outcome was mean change in visual acuity (VA) letter score (VALS) from the
randomization visit to the 6-month follow-up visit, based on the best-corrected
electronic Early Treatment Diabetic Retinopathy Study VALS (scores range from 0
100; higher scores indicate better VA). The noninferiority margin was 5 letters,
and statistical testing for noninferiority was based on a 1-sided 97.5%
confidence interval. Results: Among 362 randomized participants (mean [SD] age,
69 [12] years; 157 [43.4%] women; mean [SD] VALS at baseline, 50.3 [15.2]
[approximate Snellen VA 20/100]), 348 (96.1%) completed the month 6 follow-up
visit. At month 6, the mean VALS was 69.3 (a mean increase from baseline of 18.6)
in the bevacizumab group and 69.3 (a mean increase from baseline of 18.9) in the
aflibercept group (model-based estimate of between-group difference, -0.14; 97.5%
CI, -3.07 to infinity; P = .001 for noninferiority), meeting criteria for
noninferiority. Ocular adverse events in the aflibercept group included 4
participants with intraocular pressure (IOP) more than 10 mm Hg greater than
baseline; ocular adverse events in the bevacizumab group included 1 participant
with endophthalmitis (culture negative), 9 with IOP more than 10 mm Hg greater
than baseline, 2 with IOP higher than 35 mm Hg, and 1 with angle-closure glaucoma
not attributed to the study drug or procedure. Conclusions and Relevance: Among
patients with macular edema due to central retinal or hemiretinal vein occlusion,
intravitreal bevacizumab was noninferior to aflibercept with respect to visual
acuity after 6 months of treatment.
PMID- 28492912
TI - Auditory Verbal Working Memory as a Predictor of Speech Perception in Modulated
Maskers in Listeners With Normal Hearing.
AB - Purpose: Background noise can interfere with our ability to understand speech.
Working memory capacity (WMC) has been shown to contribute to the perception of
speech in modulated noise maskers. WMC has been assessed with a variety of
auditory and visual tests, often pertaining to different components of working
memory. This study assessed the relationship between speech perception in
modulated maskers and components of auditory verbal working memory (AVWM) over a
range of signal-to-noise ratios. Method: Speech perception in noise and AVWM were
measured in 30 listeners (age range 31-67 years) with normal hearing. AVWM was
estimated using forward digit recall, backward digit recall, and nonword
repetition. Results: After controlling for the effects of age and average pure
tone hearing threshold, speech perception in modulated maskers was related to
individual differences in the phonological component of working memory (as
assessed by nonword repetition) but only in the least favorable signal-to-noise
ratio. The executive component of working memory (as assessed by backward digit)
was not predictive of speech perception in any conditions. Conclusions: AVWM is
predictive of the ability to benefit from temporal dips in modulated maskers:
Listeners with greater phonological WMC are better able to correctly identify
sentences in modulated noise backgrounds.
PMID- 28492913
TI - Mental Health Outcomes After Having or Being Denied an Abortion-Reply.
PMID- 28492914
TI - Antibiotic Prescribing for Nonbacterial Acute Upper Respiratory Infections in
Elderly Persons.
AB - Background: Reducing inappropriate antibiotic prescribing for acute upper
respiratory tract infections (AURIs) requires a better understanding of the
factors associated with this practice. Objective: To determine the prevalence of
antibiotic prescribing for nonbacterial AURIs and whether prescribing rates
varied by physician characteristics. Design: Retrospective analysis of linked
administrative health care data. Setting: Primary care physician practices in
Ontario, Canada (January-December 2012). Patients: Patients aged 66 years or
older with nonbacterial AURIs. Patients with cancer or immunosuppressive
conditions and residents of long-term care homes were excluded. Measurements:
Antibiotic prescriptions for physician-diagnosed AURIs. A multivariable logistic
regression model with generalized estimating equations was used to examine
whether prescribing rates varied by physician characteristics, accounting for
clustering of patients among physicians and adjusting for patient-level
covariates. Results: The cohort included 8990 primary care physicians and 185 014
patients who presented with a nonbacterial AURI, including the common cold
(53.4%), acute bronchitis (31.3%), acute sinusitis (13.6%), or acute laryngitis
(1.6%). Forty-six percent of patients received an antibiotic prescription; most
prescriptions were for broad-spectrum agents (69.9% [95% CI, 69.6% to 70.2%]).
Patients were more likely to receive prescriptions from mid- and late-career
physicians than early-career physicians (rate difference, 5.1 percentage points
[CI, 3.9 to 6.4 percentage points] and 4.6 percentage points [CI, 3.3 to 5.8
percentage points], respectively), from physicians trained outside of Canada or
the United States (3.6 percentage points [CI, 2.5 to 4.6 percentage points]), and
from physicians who saw 25 to 44 patients per day or 45 or more patients per day
than those who saw fewer than 25 patients per day (3.1 percentage points [CI, 2.1
to 4.0 percentage points] and 4.1 percentage points [CI, 2.7 to 5.5 percentage
points], respectively). Limitation: Physician rationale for prescribing was
unknown. Conclusion: In this low-risk elderly cohort, 46% of patients with a
nonbacterial AURI were prescribed antibiotics. Patients were more likely to
receive prescriptions from mid- or late-career physicians with high patient
volumes and from physicians who were trained outside of Canada or the United
States. Primary Funding Source: Ontario Ministry of Health and Long-term Care,
Academic Medical Organization of Southwestern Ontario, Schulich School of
Medicine and Dentistry, Western University, and Lawson Health Research Institute.
PMID- 28492915
TI - Sildenafil Treatment in Heart Failure With Preserved Ejection Fraction: Targeted
Metabolomic Profiling in the RELAX Trial.
AB - Importance: Phosphodiesterase-5 inhibition with sildenafil compared with a
placebo had no effect on the exercise capacity or clinical status of patients
with heart failure with preserved ejection fraction (HFpEF) in the
PhosphodiesteRasE-5 Inhibition to Improve Clinical Status and Exercise Capacity
in Diastolic Heart Failure with Preserved Ejection Fraction (RELAX) clinical
trial. Metabolic impairments may explain the neutral results. Objective: To test
the hypothesis that profiling metabolites in the RELAX trial would clarify the
mechanisms of sildenafil effects and identify metabolites associated with
clinical outcomes in HFpEF. Design, Setting, and Participants: Paired baseline
and 24-week plasma samples of 160 stable outpatient individuals with HFpEF
enrolled in the RELAX clinical trial were analyzed using flow injection tandem
mass spectrometry (60 metabolites) and conventional assays (5 metabolites).
Interventions: Sildenafil (n = 79) or a placebo (n = 81) administered orally at
20 mg, 3 times daily for 12 weeks, followed by 60 mg, 3 times daily for 12 weeks.
Main Outcomes and Measures: The primary measure was metabolite level changes
between baseline and 24 weeks stratified by treatments. Secondary measures
included correlations between metabolite level changes and clinical biomarkers
and associations between baseline metabolite levels and the composite clinical
score. Results: No metabolites changed between baseline and 24 weeks in the group
treated with a placebo; however, 7 metabolites changed in the group treated with
sildenafil, including decreased amino acids (alanine and proline; median change
[25th-75th], -38.26 [-100.3 to 28.19] and -28.24 [-56.29 to 12.08], respectively;
false discovery rate-adjusted P = .01 and .03, respectively), and increased short
chain dicarboxylacylcarnitines glutaryl carnitine, octenedioyl carnitine, and
adipoyl carnitine (median change, 6.19 [-3.37 to 14.18], 2.72 [-3 to 12.57], and
10.72 [-11.23 to 29.57], respectively; false discovery rate-adjusted P = .01,
.04, and .05, respectively), and 1 long-chain acylcarnitine metabolite (palmitoyl
carnitine; median change, 7.83 [-5.64 to 26.99]; false discovery rate-adjusted P
= .03). The increases in long-chain acylarnitine metabolites and short-chain
dicarboxylacylcarnitines correlated with increases in endothelin-1 and
creatinine/cystatin C, respectively. Higher baseline levels of short-chain
dicarboxylacylcarnitine metabolite 3-hydroxyisovalerylcarnitine/malonylcarnitine
and asparagine/aspartic acid were associated with worse clinical rank scores in
both treatment groups (beta, -96.60, P = .001 and beta, -0.02, P = .01; after
renal adjustment, P = .09 and .02, respectively). Conclusions and Relevance: Our
study provides a potential mechanism for the effects of sildenafil that, through
adverse effects on mitochondrial function and endoplasmic reticulum stress, could
have contributed to the neutral trial results in RELAX. Short-chain
dicarboxylacylcarnitine metabolites and asparagine/aspartic acid could serve as
biomarkers associated with adverse clinical outcomes in HFpEF.
PMID- 28492916
TI - Myocardial Fibrosis in Duchenne and Becker Muscular Dystrophy.
PMID- 28492917
TI - Coverage of Magnetic Resonance Imaging for Patients With Cardiac Devices:
Improving the Coverage With Evidence Development Program.
PMID- 28492919
TI - Striving for Clarity About the Best Approach to Thyroid Cancer Screening and
Treatment: Is the Pendulum Swinging Too Far?
PMID- 28492918
TI - Association of a Primary Stroke Center Protocol for Suspected Stroke by Large
Vessel Occlusion With Efficiency of Care and Patient Outcomes.
AB - Importance: While prehospital triage to the closest comprehensive stroke center
(CSC) may improve the delivery of care for patients with suspected emergent large
vessel occlusion (ELVO), efficient systems of care must also exist for patients
with ELVO who first present to a primary stroke center (PSC). Objective: To
describe the association of a PSC protocol focused on 3 key steps (early CSC
notification based on clinical severity, vessel imaging at the PSC, and cloud
based image sharing) with the efficiency of care and the outcomes of patients
with suspected ELVO who first present to a PSC. Design, Setting, and
Participants: In this retrospective cohort study, 14 regional PSCs unfamiliar
with the management of patients with ELVO were instructed on the use of the
following protocol for patients presenting with a Los Angeles Motor Scale score 4
or higher: (1) notify the CSC on arrival, (2) perform computed tomographic
angiography concurrently with noncontract computed tomography of the brain and
within 30 minutes of arrival, and (3) share imaging data with the CSC using a
cloud-based platform. A total of 101 patients were transferred from regional PSCs
to the CSC between July 1, 2015, and May 31, 2016, and received mechanical
thrombectomy for acute ischemic stroke. The CSC serves approximately 1.7 million
people and partners with 14 PSCs located between 6.4 and 73.6 km away. All
consecutive patients with internal carotid artery or middle cerebral artery
occlusions transferred over an 11-month period were reviewed, and they were
divided into 2 groups based on whether the PSC protocol was partially or fully
executed. Main Outcomes and Measures: The primary outcomes were efficiency
measures including time from PSC door in to PSC door out, time from PSC door to
CSC groin puncture, and 90-day modified Rankin Scale score (range, 0-6; scores of
0-2 indicate a good outcome). Results: Although 101 patients were transferred,
only 70 patients met the inclusion criteria during the study period. The protocol
was partially executed for 48 patients (68.6%) (mean age, 77 years [interquartile
range, 65-84 years]; 22 of the 48 patients [45.0%] were women) and fully executed
for 22 patients (31.4%) (mean age, 76 years [interquartile range, 59-86 years];
13 of the 22 patients [59.1%] were women). When fully executed, the protocol was
associated with a reduction in the median time for PSC arrival to CSC groin
puncture (from 151 minutes [95% CI, 141-166 minutes] to 111 minutes [95% CI, 88
130 minutes]; P < .001). This was primarily related to an improvement in the time
from PSC door in to door out that reduced from a median time of 104 minutes (95%
CI, 82-112 minutes) to a median time of 64 minutes (95% CI, 51-71.0 minutes) (P <
.001). When the protocol was fully executed, patients were twice as likely to
have a favorable outcome (50% vs 25%, P < .04). Conclusions and Relevance: When
fully implemented, a standardized protocol at PSCs for patients with suspected
ELVO consisting of early CSC notification, computed tomographic angiography on
arrival to the PSC, and cloud-based image sharing is associated with a reduction
in time to groin puncture and improved outcomes.
PMID- 28492920
TI - Cost-effectiveness of Intravitreous Ranibizumab Compared With Panretinal
Photocoagulation for Proliferative Diabetic Retinopathy: Secondary Analysis From
a Diabetic Retinopathy Clinical Research Network Randomized Clinical Trial.
AB - Importance: The Diabetic Retinopathy Clinical Research Network Protocol S
randomized clinical trial results suggest that ranibizumab is a reasonable
treatment alternative to panretinal photocoagulation (PRP) when managing
proliferative diabetic retinopathy (PDR), with or without concomitant baseline
diabetic macular edema (DME). However, ranibizumab injections are costly. Thus,
it would be useful to examine the relative cost-effectiveness of these 2
treatment modalities. Objective: To evaluate incremental cost-effectiveness
ratios of 0.5-mg ranibizumab therapy vs PRP for PDR. Design, Setting, and
Participants: Preplanned secondary analysis using efficacy, safety, and resource
utilization data through 2 years of follow-up at 55 US sites for 213 adults with
PDR. Data were collected from February 2012 to January 2015. Interventions:
Intravitreous 0.5-mg ranibizumab at baseline and as frequently as every 4 weeks
based on a structured retreatment protocol or PRP at baseline for PDR. Eyes in
both groups could receive ranibizumab for concomitant DME. Main Outcomes and
Measures: Incremental cost-effectiveness ratios of ranibizumab compared with PRP
evaluated within 2 prespecified subgroups for the study eye: with baseline vision
impairing (Snellen equivalent 20/32 or worse) DME and without baseline vision
impairing DME. Results: The study included 305 adults with PDR, the mean age was
52 years, 44% were women, and 52% were white. Of the 46 participants with PDR and
vision-impairing DME at baseline, 21 were assigned to the ranibizumab group and
25 to the PRP group (plus ranibizumab for DME). Among the remaining participants
without baseline vision-impairing DME, 80 and 87 were in the ranibizumab and PRP
groups, respectively. For participants with and without baseline vision-impairing
DME, the incremental cost-effectiveness ratios of ranibizumab therapy compared
with PRP were $55 568/quality-adjusted life-year and $662 978/quality-adjusted
life-year, respectively, over 2 years. Conclusions and Relevance: Over 2 years,
compared with PRP, 0.5-mg ranibizumab as given in this trial is within the $50
000/quality-adjusted life-year to $150 000/quality-adjusted life-year range
frequently cited as cost-effective in the United States for eyes presenting with
PDR and vision-impairing DME, but not for those with PDR without vision-impairing
DME. Trial Registration: Clinicaltrials.gov Identifier: NCT01489189.
PMID- 28492921
TI - Interim Safety Data Comparing Ranibizumab With Panretinal Photocoagulation Among
Participants With Proliferative Diabetic Retinopathy.
PMID- 28492922
TI - Text Messaging and Protected Health Information: What Is Permitted?
PMID- 28492923
TI - Sex- and Age-Adjusted Population Analysis of Prevalence Estimates for
Hidradenitis Suppurativa in the United States.
AB - Importance: The true prevalence of hidradenitis suppurativa (HS) is unknown.
Objective: To establish standardized overall and group-specific prevalence
estimates for HS in the United States. Design, Setting, and Participants: This
retrospective analysis included a demographically heterogeneous population-based
sample of more than 48 million unique patients across all US census regions. As
of October 27, 2016, a total of 47 690 patients with HS were identified using
electronic health record data. Main Outcomes and Measures: Standardized overall
point prevalence for HS and sex-, age-, and race-specific prevalence estimates of
HS in the general US population. Results: Of the 47 690 patients with HS (26.2%
men and 73.8% women), the overall HS prevalence in the US population sample was
0.10%, or 98 per 100 000 persons (95% CI, 97-99 per 100 000 persons). The
adjusted prevalence in women was 137 per 100 000 (95% CI, 136-139 per 100 000),
more than twice that of men (58 per 100 000; 95% CI, 57-59 per 100 000; P <
.001). The prevalence of HS was highest among patients aged 30 to 39 years (172
per 100 000; 95% CI, 169-275 per 100 000) compared with all other age groups
(range, 15-150 per 100 000; P < .001). Adjusted HS prevalences among African
American (296 per 100 000; 95% CI, 291-300 per 100 000) and biracial (218 per 100
000; 95% CI, 202-235 per 100 000) patients were more than 3-fold and 2-fold
greater, respectively, than that among white patients (95 per 100 000; 95% CI, 94
96 per 100 000; P < .001). Conclusions and Relevance: Hidradenitis suppurativa is
an uncommon, but not rare, disease in the United States that disproportionately
affects female patients, young adults, and African American and biracial
patients.
PMID- 28492925
TI - Mental Health Outcomes After Having or Being Denied an Abortion.
PMID- 28492924
TI - Handheld Reflectance Confocal Microscopy for the Detection of Recurrent
Extramammary Paget Disease.
AB - Importance: Extramammary Paget disease (EMPD) is commonly refractory to surgical
and nonsurgical therapies. Identifying recurrent or persistent EMPD is
challenging because the disease is multifocal, and multiple blind scouting
biopsies are usually performed in this setting. Handheld reflectance confocal
microscopy (HRCM) has been used to diagnose and map primary EMPD and therefore
may be used to identify EMPD recurrences. Objective: To evaluate HRCM's
diagnostic accuracy in the setting of recurrent or persistent EMPD as well as its
potential diagnostic pitfalls. Design, Setting, and Participants: This
prospective case series study included patients referred to the Dermatology
Service at Memorial Sloan Kettering Cancer Center between January 1, 2014, and
December 31, 2016, with biopsy-proven EMPD in whom HRCM was used to monitor
treatment response. Five patients were included, and 22 sites clinically
concerning for recurrent or persistent disease were evaluated using HRCM and
histopathologic examination. In 2 patients, video mosaics were created to
evaluate large areas. Main Outcomes and Measures: Sensitivity and specificity of
HRCM in identifying recurrent or persistent EMPD; causes for false-negative
results according to their location, histopathologic findings, and previous
treatments. Results: Of the 22 clinically suspicious sites evaluated in 5
patients (4 men, 1 woman; median [range] age, 70 [56-77] years), 9 (40.9%) were
positive for recurrent disease on HRCM and histopathologically confirmed, and 13
(59.1%) sites were negative on HRCM, but 3 of the 13 were positive for EMPD on
histopathological examination. In general, HRCM had a sensitivity of 75% and a
specificity of 100% in identifying recurrent or persistent EMPD. False-negative
results were found in 2 patients and occurred at the margins of EMPD, close to
previous biopsy sites. Creating video mosaics (or video mosaicking) seemed to
improve the detection of EMPD. Conclusions and Relevance: Handheld reflectance
confocal microscopy is a useful auxiliary tool for diagnosing EMPD recurrences
and can be used to guide scouting biopsies, thus reducing the number of biopsies
needed to render a correct diagnosis.
PMID- 28492926
TI - Mental Health Outcomes After Having or Being Denied an Abortion.
PMID- 28492927
TI - Prevalence of Auditory Problems in Children With Feeding and Swallowing
Disorders.
AB - Purpose: Although an interdisciplinary approach is recommended for assessment and
management of feeding or swallowing difficulties, audiologists are not always
included in the interdisciplinary team. The purpose of this study is to report
the prevalence of middle ear and hearing problems in children with feeding and
swallowing disorders and to compare this prevalence with that in typical
children. Method: A total of 103 children were included in the study: 44 children
with feeding and swallowing disorders and 59 children without any such disorders.
Audiological examinations included case-history information, visualization of the
ear canals through otoscopy, middle ear evaluation through tympanometry, and
hearing screenings using an audiometer. Results: The odds of excessive cerumen (p
= .0000, small effect size), middle ear dysfunction (p = .0148, small effect
size), and hearing screening failure (p = .0000, large effect size) were 22.14%,
2.97%, and 13.5% higher, respectively, in children with feeding and swallowing
disorders compared with typically developing children. Conclusion: The
significantly higher prevalence of hearing problems in children with feeding and
swallowing disorders compared with typically developing children suggests that
inclusion of an audiologist on the interdisciplinary team is likely to improve
overall interventional outcomes for children with feeding and swallowing
disorders.
PMID- 28492928
TI - Local Changes to the Distal Femoral Growth Plate Following Injury in Mice.
PMID- 28492929
TI - Hepatitis C Virus Infection Among Reproductive-Aged Women and Children in the
United States, 2006 to 2014.
AB - Background: In the United States, hepatitis C virus (HCV) infection has increased
among young persons who inject drugs, but the extent of this epidemic among
reproductive-aged women and their children is unknown. Objective: To estimate
numbers and describe characteristics of reproductive-aged women with HCV
infection and of their offspring. Design: Analysis of the National Notifiable
Diseases Surveillance System (NNDSS) from 2006 to 2014 and the Quest Diagnostics
Health Trends national database from 2011 to 2014. Setting: United States.
Participants: 171 801 women (aged 15 to 44 years) and 1859 children (aged 2 to 13
years) with HCV infection reported to the NNDSS; 2.1 million reproductive-aged
women and 56 684 children who had HCV testing by Quest Diagnostics. Measurements:
NNDSS HCV case reports and Quest laboratory data regarding unique reproductive
aged women and children who were tested for HCV infection. Results: The number of
reproductive-aged women with acute and past or present HCV infection in the NNDSS
doubled, from 15 550 in 2006 to 31 039 in 2014. Of 581 255 pregnant women tested
by Quest from 2011 to 2014, 4232 (0.73% [95% CI, 0.71% to 0.75%]) had HCV
infection. Of children tested by Quest, 0.76% (CI, 0.69% to 0.83%) had HCV
infection, but the percentage was 3.2-fold higher among children aged 2 to 3
years (1.62% [CI, 1.34% to 1.96%]) than those aged 12 to 13 years (0.50% [CI,
0.41% to 0.62%]). Applying the Quest HCV infection rate to annual live births
from 2011 to 2014 resulted in an estimated average of 29 000 women (CI, 27 400 to
30 900 women) with HCV infection, who gave birth to 1700 infants (CI, 1200 to
2200 infants) with the infection each year. Limitations: Only a fraction of HCV
infections is detected and reported to the NNDSS. Quest data are potentially
biased, because women who are asymptomatic, do not access health care, or have
unreported risks may be less likely to be tested for HCV infection. Conclusion:
These data suggest a recent increase in HCV infection among reproductive-aged
women and may inform deliberations regarding a role for routine HCV screening
during pregnancy. Primary Funding Source: Centers for Disease Control and
Prevention.
PMID- 28492930
TI - Hearing From the Silent Epidemic.
PMID- 28492931
TI - The Controversial Epidemiology of Left Ventricular Dysfunction in Patients With
Myotonic Dystrophy Type 1-Reply.
PMID- 28492933
TI - Myocardial Fibrosis in Duchenne and Becker Muscular Dystrophy-Reply.
PMID- 28492932
TI - Population-Based Prevalence of Cerebral Cavernous Malformations in Older Adults:
Mayo Clinic Study of Aging.
AB - Importance: The prevalence of cerebral cavernous malformation (CCM) is unknown.
Case ascertainment in most previous studies was based on autopsy data or clinical
convenience samples, often without detailed clinical or radiologic information.
Objective: To determine the prevalence of CCM in a population-based sample of
older adults. Design, Setting, and Participants: This prospective imaging study
included 4721 participants aged 50 to 89 years who were enrolled between January
1, 2004, and December 15, 2015, in the Mayo Clinic Study of Aging, a
longitudinal, population-based study of residents of Olmsted County, Minnesota.
An age- and sex-stratified sampling strategy was used to randomly select
participants from Olmsted County using the medical records linkage system of the
Rochester Epidemiology Project. Participants were invited to undergo brain
magnetic resonance imaging (MRI). Of the 4721 participants, 2715 had an evaluable
MRI. All images were reviewed by a board-certified neuroradiologist, and MRI
reports were searched for the terms cavernous malformation, cavernous angioma,
and cavernoma. Two vascular neurologists reviewed MRIs, and potential CCMs were
classified using Zabramski classification. Medical records of the identified
individuals with CCM were reviewed along with their demographic information,
medical history, and any symptoms referable to the identified CCM lesion. Main
Outcomes and Measures: Prevalence of CCM and clinical and radiologic
characteristics of study participants with CCM. Results: Of the 2715 participants
who underwent MRI scans, 12 (0.44%) had CCM. With the use of inverse probability
weights to adjust for participation bias, the overall prevalence was 0.46% (95%
CI, 0.05-0.86). The age-adjusted prevalence was found to be 0.61% (95% CI, 0
1.47) for the 50- to 59-year age group, 0.17% (95% CI, 0-0.50) for the 60- to 69
year age group, 0.45% (95% CI, 0.09-0.81) for the 70- to 79-year age group, and
0.58% (95% CI, 0-1.29) for the 80- to 89-year age group. The sex-adjusted
prevalence was 0.41% (95% CI, 0-1.00) for women and 0.51% (95% CI, 0-1.07) for
men. Observed frequencies were similar in men and women, with a slight male
predominance. Of the 12 participants with CCM, 9 (75%) had a single Zabramski
type 2 lesion in a supratentorial location. Only 1 participant (0.037%) was
symptomatic from the CCM during the study period. Conclusions and Relevance: The
findings and data from this study are important for determining the potential
number of patients available for cohort studies and anticipated clinical trials
in older patients with CCM.
PMID- 28492934
TI - Mohs Micrographic Surgery Use in the United States Based on Medicare Data-Reply.
PMID- 28492936
TI - Nonsurgical Rhinoplasty.
PMID- 28492935
TI - Employer Reactions to Adductor Spasmodic Dysphonia: Exploring the Influence of
Symptom Severity and Disclosure of Diagnosis During a Simulated Telephone
Interview.
AB - Purpose: The purpose of this study was to determine the influence of symptom
severity and disclosure of adductor spasmodic dysphonia (ADSD) on the perceptions
of human resource personnel members (HRPs) during a simulated phone interview.
Method: One female speaker with ADSD was recorded reading an interview script at
two time points: (a) pre-BOTOX injection (severe), and (b) post-BOTOX injection
(mild). Thirty-two HRPs evaluated the recording in one of the two conditions via
a qualitative structured interview. HRPs gave their recommendations regarding
when and how to disclose ADSD. Results: In the mild condition, no HRP perceived
that the applicant had a voice disorder. Disclosure was not recommended as often,
as an impairment was not initially noticed. However, 15/16 HRPs commented on the
applicant's voice in the severe condition, with most suspecting she was a smoker
or had lung/throat cancer. Disclosure in the severe condition was recommended
more often, as it clarified symptoms that were noted at the outset. Conclusions:
Symptom severity in ADSD influences employer perceptions during the phone
interview process. Incorrect assumptions may be made about applicants with severe
symptoms, and apparentness of symptoms influences whether or not disclosure is
recommended. Results have implications for counseling individuals with ADSD who
are navigating the job interview process.
PMID- 28492937
TI - Association Between Medication Use for Attention-Deficit/Hyperactivity Disorder
and Risk of Motor Vehicle Crashes.
AB - Importance: Motor vehicle crashes (MVCs) are a major public health problem.
Research has demonstrated that individuals with attention-deficit/hyperactivity
disorder (ADHD) are more likely to experience MVCs, but the effect of ADHD
medication treatment on the risk of MVCs remains unclear. Objective: To explore
associations between ADHD medication use and risk of MVCs in a large cohort of
patients with ADHD. Design, Setting, and Participants: For this study, a US
national cohort of patients with ADHD (n = 2 319 450) was identified from
commercial health insurance claims between January 1, 2005, and December 31,
2014, and followed up for emergency department visits for MVCs. The study used
within-individual analyses to compare the risk of MVCs during months in which
patients received ADHD medication with the risk of MVCs during months in which
they did not receive ADHD medication. Exposures: Dispensed prescription of ADHD
medications. Main Outcomes and Measures: Emergency department visits for MVCs.
Results: Among 2 319 450 patients identified with ADHD, the mean (SD) age was
32.5 (12.8) years, and 51.7% were female. In the within-individual analyses, male
patients with ADHD had a 38% (odds ratio, 0.62; 95% CI, 0.56-0.67) lower risk of
MVCs in months when receiving ADHD medication compared with months when not
receiving medication, and female patients had a 42% (odds ratio, 0.58; 95% CI,
0.53-0.62) lower risk of MVCs in months when receiving ADHD medication. Similar
reductions were found across all age groups, across multiple sensitivity
analyses, and when considering the long-term association between ADHD medication
use and MVCs. Estimates of the population-attributable fraction suggested that up
to 22.1% of the MVCs in patients with ADHD could have been avoided if they had
received medication during the entire follow-up. Conclusions and Relevance: Among
patients with ADHD, rates of MVCs were lower during periods when they received
ADHD medication. Considering the high prevalence of ADHD and its association with
MVCs, these findings warrant attention to this prevalent and preventable cause of
mortality and morbidity.
PMID- 28492939
TI - Treatment of Macular Edema Due to Central Retinal Vein Occlusion: Another Score
for Repackaged Bevacizumab.
PMID- 28492938
TI - Association Between Breast Milk Bacterial Communities and Establishment and
Development of the Infant Gut Microbiome.
AB - Importance: Establishment of the infant microbiome has lifelong implications on
health and immunity. Gut microbiota of breastfed compared with nonbreastfed
individuals differ during infancy as well as into adulthood. Breast milk contains
a diverse population of bacteria, but little is known about the vertical transfer
of bacteria from mother to infant by breastfeeding. Objective: To determine the
association between the maternal breast milk and areolar skin and infant gut
bacterial communities. Design, Setting, and Participants: In a prospective,
longitudinal study, bacterial composition was identified with sequencing of the
16S ribosomal RNA gene in breast milk, areolar skin, and infant stool samples of
107 healthy mother-infant pairs. The study was conducted in Los Angeles,
California, and St Petersburg, Florida, between January 1, 2010, and February 28,
2015. Exposures: Amount and duration of daily breastfeeding and timing of solid
food introduction. Main Outcomes and Measures: Bacterial composition in maternal
breast milk, areolar skin, and infant stool by sequencing of the 16S ribosomal
RNA gene. Results: In the 107 healthy mother and infant pairs (median age at the
time of specimen collection, 40 days; range, 1-331 days), 52 (43.0%) of the
infants were male. Bacterial communities were distinct in milk, areolar skin, and
stool, differing in both composition and diversity. The infant gut microbial
communities were more closely related to an infant's mother's milk and skin
compared with a random mother (mean difference in Bray-Curtis distances, 0.012
and 0.014, respectively; P < .001 for both). Source tracking analysis was used to
estimate the contribution of the breast milk and areolar skin microbiomes to the
infant gut microbiome. During the first 30 days of life, infants who breastfed to
obtain 75% or more of their daily milk intake received a mean (SD) of 27.7%
(15.2%) of the bacteria from breast milk and 10.3% (6.0%) from areolar skin.
Bacterial diversity (Faith phylogenetic diversity, P = .003) and composition
changes were associated with the proportion of daily breast milk intake in a dose
dependent manner, even after the introduction of solid foods. Conclusions and
Relevance: The results of this study indicate that bacteria in mother's breast
milk seed the infant gut, underscoring the importance of breastfeeding in the
development of the infant gut microbiome.
PMID- 28492949
TI - The Role of Skin Care in Optimizing Treatment of Acne and Rosacea.
AB - A triad approach to the treatment of acne and rosacea has been recommended. This
integrated management approach includes patient education, selection of
therapeutic agents, and initiation of an appropriate skin care regime. Proper
skin care in patients undergoing treatment of both acne and rosacea includes use
of products formulated for sensitive skin that cleanse, moisturize and
photoprotect the skin. Both acne and rosacea are associated with epidermal
barrier dysfunction, which can be mitigated by suitable skin care practices.
Appropriate skin care recommendations for patients with acne and rosacea will be
discussed.
PMID- 28492950
TI - Psychoactive constituents of cannabis and their clinical implications: a
systematic review.
AB - Objective This systematic review aims to summarize current evidence on which
naturally present cannabinoids contribute to cannabis psychoactivity, considering
their reported concentrations and pharmacodynamics in humans. Design Following
PRISMA guidelines, papers published before March 2016 in Medline, Scopus
Elsevier, Scopus, ISI-Web of Knowledge and COCHRANE, and fulfilling established a
priori selection criteria have been included. Results In 40 original papers,
three naturally present cannabinoids (?-9-Tetrahydrocannabinol, ?-8
Tetrahydrocannabinol and Cannabinol) and one human metabolite (11-OH-THC) had
clinical relevance. Of these, the metabolite produces the greatest psychoactive
effects. Cannabidiol (CBD) is not psychoactive but plays a modulating role on
cannabis psychoactive effects. The proportion of 9-THC in plant material is
higher (up to 40%) than in other cannabinoids (up to 9%). Pharmacodynamic reports
vary due to differences in methodological aspects (doses, administration route
and volunteers' previous experience with cannabis). Conclusions Findings reveal
that 9-THC contributes the most to cannabis psychoactivity. Due to lower
psychoactive potency and smaller proportions in plant material, other
psychoactive cannabinoids have a weak influence on cannabis final effects.
Current lack of standard methodology hinders homogenized research on cannabis
health effects. Working on a standard cannabis unit considering 9-THC is
recommended.
PMID- 28492951
TI - Information and Communications Technologies (ICT): Problematic use of Internet,
video games, mobile phones, instant messaging and social networks using MULTICAGE
TIC.
AB - Use/abuse of Information and Communications Technologies (ICT) has in recent
years become a topic of great interest. Current discussion addresses whether it
must be considered addictive behaviour and if it is a problem that primarily
affects adolescents and youth. This study aims to understand the problems that
affect people of all ages in controlling the use of these ICTs and whether they
are related to mental health problems, stress and difficulties in executive
control of behaviour. A survey was administered through social networks and
email, using the MULTICAGE-ICT, a questionnaire that explores problems in the use
of Internet, mobile phones, video games, instant messaging and social networks.
Additionally, the Prefrontal Symptom Inventory, General Health Questionnaire and
Perceived Stress Scale were administered. The sample was comprised of 1,276
individuals of all ages from different Spanish-speaking countries. The results
indicate that about 50% of the sample, regardless of age or other variables,
presents significant problems with the use of these technologies, and that these
problems are directly related to symptoms of poor prefrontal functioning, stress
and mental health problems. The results reveal the need for reconsidering whether
we are facing an addictive behaviour or a new problem demanding environmental,
psychological, sociological and sociopolitical explanations; therefore, it is
necessary to reformulate actions to be implemented to address and refocus our
understanding of the problem.
PMID- 28492952
TI - Brief Sensation Seeking Scale: Latent structure of 8-item and 4-item versions in
Peruvian adolescents.
AB - This research intended to validate two brief scales of sensations seeking with
Peruvian adolescents: the eight item scale (BSSS8; Hoyle, Stephenson, Palmgreen,
Lorch, y Donohew, 2002) and the four item scale (BSSS4; Stephenson, Hoyle,
Slater, y Palmgreen, 2003). Questionnaires were administered to 618 voluntary
participants, with an average age of 13.6 years, from different levels of high
school, state and private school in a district in the south of Lima. It analyzed
the internal structure of both short versions using three models: a)
unidimensional (M1), b) oblique or related dimensions (M2), and c) the bifactor
model (M3). Results show that both instruments have a single dimension which best
represents the variability of the items; a fact that can be explained both by the
complexity of the concept and by the small number of items representing each
factor, which is more noticeable in the BSSS4. Reliability is within levels found
by previous studies: alpha: .745 = BSSS8 and BSSS4 =. 643; omega coefficient:
.747 in BSSS8 and .651 in BSSS4. These are considered suitable for the type of
instruments studied. Based on the correlation between the two instruments, it was
found that there are satisfactory levels of equivalence between the BSSS8 and
BSSS4. However, it is recommended that the BSSS4 is mainly used for research and
for the purpose of describing populations.
PMID- 28492953
TI - Muscle dysmorphia: detection of the use-abuse of anabolic adrogenic steroids in a
Spanish sample.
AB - Due to a distortion in the body image, the people who suffer from muscle
dysmorphia have the self-perception of being less muscular than they currently
are. With the aim of increasing their muscular development, they resort to the
use of AAS. The purpose of the present study is to know the prevalence of the use
of AAS in a Spanish sample affected by muscle dysmorphia. 562 male and 172 female
bodybuilders and weightlifters were provided with different questionnaires in
order to know, firstly, if they suffered from this disorder and, secondly, the
percentage of the participants affected who use these substances. Decision trees
and regression was applied to create explanatory models for muscle dysmorphia (R
= 0.78 and R2 = 0.62). The results show that almost 50% of the participants, male
and female, affected by this disorder use this kind of drugs.
PMID- 28492954
TI - Design and validation of a Cannabis Use Intention Questionnaire (CUIQ) for
adolescents.
AB - In Spain, one in four 14 to 18-year-old adolescents has used cannabis during the
last twelve months. Demand for treatment has increased in European countries.
These facts have prompted the development of preventive interventions that
require screening tools in order to identify the vulnerable population and to
properly asses the efficacy of such interventions. The Theory of Planned
Behaviour (TPB), widely used to forecast behavioural intention, has also
demonstrated a good predictive capacity in addictions. The aim of this study is
to design and validate a Cannabis Use Intention Questionnaire (CUIQ) based on
TPB. 1,011 teenagers answered a set of tests to assess attitude towards use,
subjective norms, self-efficacy towards non-use, and intention to use cannabis.
CUIQ had good psychometric properties. Structural Equation Modelling results
confirm the predictive model on intention to use cannabis in the Spanish
adolescent sample, classified as users and non-users, explaining 40% of variance
of intention to consume. CUIQ is aimed at providing a better understanding of the
psychological processes that lead to cannabis use and allowing the evaluation of
programmes. This can be particularly useful for improving the design and
implementation of selective prevention programmes.
PMID- 28492955
TI - The association of Self-concept with Substance Abuse and Problematic Use of Video
Games in University Students: A Structural Equation Model.
AB - This study aims to define and contrast an explanatory model of consumption of
alcohol, tobacco consumption, and problematic use of video games based on self
concept and its dimensions in a sample of university students. The research was
conducted with a sample of 490 students from the province of Granada (Spain),
aged between 20 and 29 years (M = 22.80 +/- 3.63), with a homogeneous
distribution by gender. The instruments used were the Self-concept Form-5
Questionnaire (Garcia & Musitu, 1999), the Alcohol Use Disorders Identification
Test (Saunders, Aasland, Babor, De la Fuente, & Grant, 1993), the Fagerstrom Test
for Nicotine Dependence (Heatherton, Kozlowski, Frecker, & Fagerstrom, 1991) and
the Questionnaire for Experiences Related to Video Games (Chamarro et al., 2014).
A model of structural equations was estimated, which was adjusted properly,
chi2(8) = 19.843, p = .011; CFI = .963, NFI = .943, IFI = .965, RMSEA = .055. As
main results, a positive relationship between social and physical self-concept
and consumption of alcohol was obtained, as well as a negative relationship
between social self-concept and problematic use of videogames. Academic dimension
was negatively related to alcohol and video game use. Furthermore, alcohol
consumption was positively related to tobacco consumption and use of video games.
It is concluded that levels of self-concept may represent a risk factor in
substance abuse and digital leisure, and their study and consideration are
appropriate.
PMID- 28492956
TI - Relationship between the rs1414334 C/G polymorphism in the HTR2C gene and smoking
in patients treated with atypical antipsychotics.
AB - An association has been found between the C allele of the rs1414334 polymorphism
in the HTR2C gene and the metabolic syndrome in psychiatric patients. However, no
study has yet evaluated whether this allele is associated with smoking. To assess
this issue, therefore, we performed a cross-sectional study with a sample of 166
adult patients treated with atypical antipsychotics in 2012-2013 in a region of
Spain. The primary variable was the presence of the C allele of the rs1414334
polymorphism in the HTR2C gene. Secondary variables were the number of pack-years
(number of cigarettes per day x number of smoking years / 20), age, gender,
schizophrenia, years since diagnosis, metabolic syndrome criteria and SCORE. A
stepwise binary logistic regression model was constructed to determine
associations between primary and secondary variables and their area under the ROC
curve (AUC) was calculated. Of the total sample, 33 patients (19.9%) had the C
allele of the polymorphism analyzed. Mean cigarette consumption was 11.6 pack
years. The multivariate analysis showed the following factors as associated with
the polymorphism: higher cigarette consumption, being a woman, and not having
abdominal obesity. The AUC was 0.706. An association was found between increased
cigarette consumption over the years and the presence of the C allele of the
rs1414334 polymorphism in the HTR2C gene.
PMID- 28492957
TI - Screening of alcohol use disorders in psychiatric outpatients: influence of
gender, age, and psychiatric diagnosis.
AB - Alcohol use disorders (AUD) are 2 times higher among psychiatric patients than in
the general population. The under-recognition of this dual diagnosis can entail
several negative outcomes. Early assessment with a screening tool like the CAGE
questionnaire could be an opportunity to improve patients' prognoses. The
objective of this study is to assess AUD risk in an outpatient psychiatric sample
with a modified CAGE, considering the influence of age, gender and clinical
psychiatric diagnosis. An observational, multicentric, descriptive study was
carried out. The 4-item CAGE scale, camouflaged in a healthy lifestyle
questionnaire, was implemented, using a cut-off point of one. 559 outpatients
were assessed. 54% were female and the average age was 50.07 years. 182 patients
presented a CAGE score >=1 (45.1% of men and 21.9% of women). Gender was the
strongest predictor of a positive result in CAGE, as men were 3.03 times more
likely to score >=1 on the CAGE questionnaire (p < .001, 95% CI: 0.22-0.49).
Patients with bipolar and personality disorders had the highest rates of CAGE
scores >=1 (45.2 and 44.9%, respectively), with a significant association between
diagnosis and a positive score (p = .002). Patients above 60 years were 2.5 times
less likely to score >=1 on the CAGE (p = .017, 95% CI: 0.19-0.85). Specific
screening questionnaires, like the CAGE scale, can be an easy and useful tool in
the assessment of AUD risk in psychiatric outpatients. Male patients with a
bipolar or personality disorder present a higher risk of AUD.
PMID- 28492958
TI - Psychometric validation of the POSIT for screening alcohol and other drugs risk
consumption among adolescents.
AB - Early detection of alcohol and drug abuse among adolescents is decisive not only
for rapid referral and intervention in cases of risk, but also as an indicator
for use in the evaluation of prevention programs and public policies to reduce
consumption. One of the most widely-used screening instruments in the world is
the Problem Oriented Screening Instrument for Teenagers (POSIT) (Rahdert, 1991),
whose substance use and abuse subscale (POSITUAS) is a brief tool of enormous
applied potential. However, there is still no empirical validation study that
would ensure its good psychometric performance in Spain. The aim of this paper is
to analyse the psychometric properties of POSITUAS among Spanish adolescents. For
this purpose, 569 students aged between 12 and 18 years (M = 14.71; SD = 1.79)
were personally interviewed. The study sample was selected through two-stage
sampling. The results obtained, using the Adolescent Diagnostic Interview
(Winters & Henly, 1993) as the gold criterion, allow us to inform that the
Spanish version of the POSITUAS has excellent psychometric behaviour, both at the
level of internal consistency (a = .82) as well as regards sensitivity (94.3%)
and specificity (83.9%), with an area under the ROC curve of .953. Also, the
realisation of a Confirmatory Factor Analysis allows for verifying the one
dimensional character of the scale. As a result, POSITUAS is made available to
researchers and professionals in the field of addictive behaviours for use with a
minimum of psychometric guarantees.
PMID- 28492959
TI - The relationship between consumption of alcohol and other drugs and problematic
Internet use among adolescents.
AB - Alcohol and drug use among adolescents has been causing great concern for decades
in Spain and in the European Union as a whole. In addition, the technology boom
experienced over the last two decades has contributed to the emergence of a new
public healthcare issue: problematic Internet use. The increasing importance that
both problems have been gaining in recent years has led some authors to analyze
the relationship between alcohol and the consumption of other drugs alongside
problematic Internet use, and to provide relevant empirical evidence. Based on a
sample of 3,882 Spanish adolescents aged between 12 and 18, the results obtained
confirm that there is a relationship between the consumption of alcohol (measured
by the AUDIT) and other drugs (measured by the CRAFFT and the CAST), and
problematic Internet use (measured by the EUPI-a). Problematic Internet users
among them not only have more significant levels of substance use, but also a
three-times greater chance of developing hazardous drug use (39.4% vs 13.3%).
This highlights the need to develop transversal prevention capable of acting on
the common variables to both issues, beyond developing programs focused on
specific behaviors. In this sense, values-based education and life skills
training should be given priority in prevention.
PMID- 28492961
TI - Chemsex. An emergent phenomenon.
AB - Letter to the editor.
PMID- 28492960
TI - Dual diagnosis in Depression: treatment recommendations.
AB - Comorbidity between substance use disorders (SUD) and major depression (MD) is
the most common dual pathology in the field of addiction to substances and has
prevalence rates ranging between 12% and 80%, which complicates the response to
treatment and worsens the prognosis of patients. Differentiating between
diagnoses of induced depressive episodes and primary depressive episodes
concurrent to substance use is especially relevant for therapeutic management.
This article presents the state of the art of the currently available
pharmacologic treatments of comorbid depression in patients with SUD, taking into
account the safety and risk of abuse of antidepressant drugs. Due to the fact
that comorbidity of MD and SUD is frequent and presents greater
psychopathological and medical severity, as well as worse social functioning, it
is crucial to treat MD and SUD simultaneously using the integrated treatment
model and not to treat both conditions separately.
PMID- 28492962
TI - Self-quitting in a Spanish sample. An exploratory study.
AB - Letter to the editor.
PMID- 28492963
TI - Assessing the decision-making capacity of the addicted population to take part in
research: myths, barriers, and benefits.
AB - Letter to the editor.
PMID- 28492964
TI - Studies into severe famine in early life and diabetes in adulthood: the need to
control for differences in participant age and location.
PMID- 28492965
TI - Role of ICG-99mTc-nanocolloid for sentinel lymph node detection in cervical
cancer: a pilot study.
AB - PURPOSE: Sentinel lymph node biopsy (SLNB) can be used for nodal staging in early
cervical cancer. For this purpose, the tracers most commonly used are
radiotracers based on technetium. For the last decade, indocyanine green (ICG)
has been used as a tracer for SLNB in other malignancies with excellent results
and, more recently, a combination of ICG and a radiotracer has been shown to have
the advantages of both tracers. The aim of this study was to evaluate the role of
ICG-99mTc-nanocolloid in SLN detection in patients with cervical cancer. METHODS:
This prospective study included 16 patients with cervical cancer. The hybrid
tracer was injected the day (19-21 h) before surgery for planar and SPECT/CT
lymphoscintigraphy. Blue dye was administered periorificially in 14 patients.
SLNs were removed according to their distribution on lymphoscintigraphy and when
radioactive, fluorescent and/or stained with blue dye. Nodal specimens were
pathologically analysed for metastases including by immunochemistry. RESULTS:
Lymphoscintigraphy and SPECT/CT showed drainage in all patients. A total of 69
SLNs were removed, of which 66 were detected by their radioactivity signal and 67
by their fluorescence signal. Blue dye identified only 35 SLNs in 12 of the 14
patients (85.7%). All patients showed bilateral pelvic drainage. Micrometastases
were diagnosed in two patients, and were the only lymphatic nodes involved.
CONCLUSIONS: SLNB with ICG-99mTc-nanocolloid is feasible and safe in patients
with early cervical cancer. This hybrid tracer provided bilateral SLN detection
in all patients and a higher detection rate than blue dye, so it could become an
alternative to the combined technique.
PMID- 28492966
TI - Complex Genes Are Preferentially Retained After Whole-Genome Duplication in
Teleost Fish.
AB - Gene duplication generates new genetic material which, if retained after
duplication, may contribute to organismal evolution. A whole-genome duplication
occurred in the ancestry of teleost fish and consequently there are many
duplicated genes in teleost genomes. Indeed, it has been proposed that the
evolutionary diversification of teleost fish may have been stimulated by the fish
specific genome duplication (FSGD). However, it is not clear which factors
determine which genes are retained as duplicate copies and which return to a
singleton state after duplication. In the present study, gene complexity, in
terms of encoded protein length and functional domain number, is compared between
duplicate and singleton genes for nine well-annotated teleost genomes. A total of
933 gene families with retained duplicates and 4590 singleton gene families are
analysed. Genes with retained duplicates are found to be significantly longer
(27.9-38.2%) and to have more functional domains (20.5-26.5%) than singleton
genes in all the nine teleost genomes, suggesting that genes encoded longer
proteins with and more functional domains were preferentially retained after
whole-genome duplication in teleosts. This differential retention of duplicated
genes will have increased the genomic complexity of teleost fish after FSGD
which, together with differential duplicated gene retention as a lineage
splitting force, may have greatly contributed to the successful diversification
of teleost fish.
PMID- 28492967
TI - A Test for Gene Flow among Sympatric and Allopatric Hawaiian Picture-Winged
Drosophila.
AB - The Hawaiian Drosophila are one of the most species-rich endemic groups in Hawaii
and a spectacular example of adaptive radiation. Drosophila silvestris and D.
heteroneura are two closely related picture-winged Drosophila species that occur
sympatrically on Hawaii Island and are known to hybridize in nature, yet exhibit
highly divergent behavioral and morphological traits driven largely through
sexual selection. Their closest-related allopatric species, D. planitibia from
Maui, exhibits hybrid male sterility and reduced behavioral reproductive
isolation when crossed experimentally with D. silvestris or D. heteroneura. A
modified four-taxon test for gene flow was applied to recently obtained genomes
of the three Hawaiian Drosophila species. The analysis indicates recent gene flow
in sympatry, but also, although less extensive, between allopatric species. This
study underscores the prevalence of gene flow, even in taxonomic groups
considered classic examples of allopatric speciation on islands. The potential
confounding effects of gene flow in phylogenetic and population genetics
inference are discussed, as well as the implications for conservation.
PMID- 28492968
TI - [Monitoring methods and their results in environmental medicine - implications
for medical counsellors].
AB - Besides effect and environmental monitoring, human biomonitoring (HBM) offers an
attractive method for analyzing the distribution and intensity of anthropogenic
environmental pollutants in individuals or in particular groups of the
population. However, no assessment values of comparable reliability are available
to enable an interpretation of the results of environmental studies from the
viewpoint of environmental health. This must be taken into account when reporting
findings of such studies as well as in medical consultation, in order to avoid
overdiagnosis and unnecessary anxiety for the participant. In medical practice,
care should be taken when dealing with monitoring results outside the normal
range! Environmental or biomonitoring results provide only a part of the
available information alongside medical history and clinical examinations. In the
case of tests performed for private interests as well as tests carried out within
the framework of an epidemiological environmental survey, communication of
results and findings can be problematic. In epidemiological studies, a close co
operation between the participant's consultant physician and physicians
conducting the study is beneficial in order to ensure professional advisory
counselling for subjects with results outside the normal range.
PMID- 28492969
TI - ?
PMID- 28492970
TI - Oral and intravenous steroids for multiple sclerosis relapse: a systematic review
and meta-analysis.
AB - Glucocorticoids are the standard of care for multiple sclerosis (MS) relapses,
but the most desirable route of administration is still matter of debate. The aim
of the study was to compare the efficacy and safety of oral versus intravenous
steroids for treatment of acute relapses in patients with MS. Randomized or quasi
randomized, parallel group trials with direct comparison between oral and
intravenous steroid treatment in MS patients with acute relapse were identified
through a systematic literature search. Six trials were included involving 419
participants, 210 for oral, and 209 for intravenous groups, respectively. The
weighted mean differences (WMDs) in the Kurtzke's Expanded Disability Status
Scale (EDSS) score reduction between the oral and intravenous groups were 0.32 [(
0.09 to 0.73); p = 0.129] and 0.11 [(-0.12 to 0.33); p = 0.355] at 1 and 4 weeks
after treatment, respectively. The risk ratios (RRs) for improvement by at least
one EDSS point were 0.79 [(0.37-1.68); p = 0.539] at week 1 and 0.92 (0.76-1.12);
p = 0.400] at week 4. There were no differences in the relapse rate and relapse
freedom at 6 months between groups. The WMDs in the mean percentage reduction of
Gadolinium-enhancing lesions between oral and intravenous arms were 0.14 (-0.02,
0.29); p = 0.083] and 0.04 (-0.19, 0.28); p = 0.705] at 1 and 4 weeks from
treatment. Among the adverse events, insomnia was significantly associated with
the oral route of steroid administration [RR 1.25 (1.07-1.46); p = 0.005]. In
adult patients with acute MS relapse, there were no clear-cut differences in the
efficacy and overall tolerability between oral and intravenous steroids.
PMID- 28492971
TI - Current conservation status of Germain's langur (Trachypithecus germaini) in
Vietnam.
AB - Following the split of the silvered langurs of Indochina into two species based
on molecular and phenotypic data, there is a need to reevaluate their
distribution and update their conservation status. Here, we report the
distribution and assess the population size of Germain's langur (Trachypithecus
germaini) within its known range across Vietnam. We confirmed this species at six
of seven survey sites in different habitats within three provinces in the Mekong
Delta Region, including semi-evergreen forest at the Seven Mountains of An Giang
Province, mangrove forest in Ngoc Hien and Nam Can Districts and Melaleuca forest
in U Minh Ha National Park of Ca Mau Province, and limestone forest at Kien Luong
Karst Area and semi-evergreen and evergreen forests at Phu Quoc National Park of
Kien Giang Province. We found no evidence of this species in Mui Ca Mau National
Park, Ca Mau Province where it was previously reported. We conservatively
estimate that the total population of Germain's langurs in Vietnam consists of
362-406 individuals, with the largest population found in the Kien Luong Karst
Area. Hunting and habitat loss are severely impacting Germain's langur, resulting
in the extirpation of the population in Mui Ca Mau National Park and small,
isolated populations in the Seven Mountains and Ngoc Hien and Nam Can Districts.
However, the ability of this species to inhabit a wide range of forest types, and
its increasing population sizes in Phu Quoc National Park and Kien Luong Karst
Area, provide signs of hope that continued conservation actions may help in its
long-term survival.
PMID- 28492972
TI - Performance of the pediatric logistic organ dysfunction (PELOD) and (PELOD-2)
scores in a pediatric intensive care unit of a developing country.
AB - : The study aimed to compare two scores: the pediatric logistic organ dysfunction
(PELOD) with its updated version (PELOD-2) in describing the severity of organ
dysfunction in pediatric intensive care unit (PICU) and assess the performance of
PELOD-2 in the Egyptian population. A prospective cohort study of 200 patients
consecutively admitted to PICU between July 2015 and A 2016 was included. The
median age was 6 months, and the male to female ratio was 1.04. The median length
of PICU stay was 4 days. The overall predicted number of deaths using PELOD was
76 patients whereas, by PELOD-2, it was 50 patients. The observed mortality was
50 patients. The area under the receiving operating characteristic curve was
excellent for both PELOD and PELOD-2 (0.93 and 0.91, respectively). The Hosmer
and Lemeshow goodness-of-fit test showed good calibration of PELOD-2 (chi 2 =
9.9, p = 0.27), while PELOD showed poor calibration (chi 2 = 42, p = 0.000) in
the same studied group. CONCLUSION: Both scores had excellent discrimination.
PELOD-2 is reproducible and easier to perform and had better calibration compared
to PELOD score. What is Known: * Pediatric logistic organ dysfunction (PELOD)
score was developed 1999 and validated in 2003 to describe the organ dysfunction
severity in pediatric intensive care units. * A new and easier version of (PELOD
2) was developed 2013 in France and Belgium to replace the old score. It is
important to assess the performance of the new score in other population else
than the original. What is New: In an Egyptian pediatric intensive care, the
performance of the score revealed: * PELOD-2 was an excellent discriminatory
score comparable to the original score. * PELOD-2 calibrated well in the Egyptian
population while the old score had poor calibration.
PMID- 28492973
TI - Fast therapeutic hypothermia prevents post-cardiac arrest syndrome through
cyclophilin D-mediated mitochondrial permeability transition inhibition.
AB - The opening of the mitochondrial permeability transition pore (PTP), which is
regulated by the matrix protein cyclophilin D (CypD), plays a key role in the
pathophysiology of post-cardiac arrest (CA) syndrome. We hypothesized that
therapeutic hypothermia could prevent post-CA syndrome through a CypD-mediated
PTP inhibition in both heart and brain. In addition, we investigated whether
specific pharmacological PTP inhibition would confer additive protection to
cooling. Adult male New Zealand White rabbits underwent 15 min of CA followed by
120 min of reperfusion. Five groups (n = 10-15/group) were studied: control group
(CA only), hypothermia group (HT, hypothermia at 32-34 degrees C induced by
external cooling at reperfusion), NIM group (injection at reperfusion of 2.5
mg/kg NIM811, a specific CypD inhibitor), HT + NIM, and sham group. The following
measurements were taken: hemodynamics, echocardiography, and cellular damage
markers (including S100beta protein and troponin Ic). Oxidative phosphorylation
and PTP opening were assessed on mitochondria isolated from both brain and heart.
Acetylation of CypD was measured by immunoprecipitation in both the cerebral
cortex and myocardium. Hypothermia and NIM811 significantly prevented
cardiovascular dysfunction, pupillary areflexia, and early tissue damage.
Hypothermia and NIM811 preserved oxidative phosphorylation, limited PTP opening
in both brain and heart mitochondria and prevented increase in CypD acetylation
in brain. There were no additive beneficial effects in the combination of NIM811
and therapeutic hypothermia. In conclusion, therapeutic hypothermia limited post
CA syndrome by preventing mitochondrial permeability transition mainly through a
CypD-dependent mechanism.
PMID- 28492974
TI - Influence of drinking water salinity on carcass characteristics and meat quality
of Santa Ines lambs.
AB - This study aimed to evaluate the effects of different salinity levels in drinking
water on the quantitative and qualitative characteristics of lamb carcass and
meat. Ram lambs (n = 32) were distributed in a completely randomized design with
four levels of salinity in the drinking water (640 mg of total dissolved solids
(TDS)/L of water, 3188 mg TDS/L water, 5740 mg TDS/L water, and 8326 mg TDS/L
water). After slaughter, blending, gutting, and skinning the carcass, hot and
biological carcass yields were obtained. Then, the carcasses were cooled at 5
degrees C for 24 h, and then, the morphometric measurements and the cold carcass
yield were determined and the commercial cuts made. In the Longissimus lumborum
muscle color, water holding capacity, cooking loss, shear force, and chemical
composition were determined. The yields of hot and cold carcass (46.10 and
44.90%), as well as losses to cooling (2.40%) were not affected (P > 0.05) by the
salinity levels in the water ingested by the lambs. The meat shear force was 3.47
kg/cm2 and moisture, crude protein, ether extract, and ash were 73.62, 22.77,
2.5, and 4.3%, respectively. It is possible to supply water with salinity levels
of up to 8326 mg TDS/L, because it did not affect the carcass and meat
characteristics of Santa Ines lambs.
PMID- 28492975
TI - Practice makes perfect: familiarity of task determines success in solvable tasks
for free-ranging dogs (Canis lupus familiaris).
AB - Domestic dogs' (Canis lupus familiaris) socio-cognitive faculties have made them
highly sensitive to human social cues. While dogs often excel at understanding
human communicative gestures, they perform comparatively poorly in problem
solving and physical reasoning tasks. This difference in their behaviour could be
due to the lifestyle and intense socialization, where problem solving and
physical cognition are less important than social cognition. Free-ranging dogs
live in human-dominated environments, not under human supervision and are less
socialized. Being scavengers, they often encounter challenges where problem
solving is required in order to get access to food. We tested Indian street dogs
in familiar and unfamiliar independent solvable tasks and quantified their
persistence and dependence on a novel human experimenter, in addition to their
success in solving a task. Our results indicate that free-ranging dogs succeeded
and persisted more in the familiar task as compared to the unfamiliar one. They
showed negligible amount of human dependence in the familiar task, but showed
prolonged gazing and considerable begging behaviour to the human experimenter in
the context of the unfamiliar task. Cognitive abilities of free-ranging dogs thus
play a pivotal role in determining task-associated behaviours based on
familiarity. In addition to that, these dogs inherently tend to socialize with
and depend on humans, even if they are strangers. Our results also illustrate
free-ranging dogs' low competence at physical cognitive tasks.
PMID- 28492976
TI - Squalene promotes cholesterol homeostasis in macrophage and hepatocyte cells via
activation of liver X receptor (LXR) alpha and beta.
AB - OBJECTIVE: To examine the effect of squalene on liver X receptors (LXRs) that
regulate target genes associated with reverse cholesterol transport and thus
control whole-body cholesterol homeostasis. RESULTS: To examine the effect of
squalene on liver X receptors (LXRs) that regulate target genes associated with
reverse cholesterol transport and thus control whole-body cholesterol
homeostasis. Squalene significantly stimulated the transactivation of liver X
receptor modulator LXRalpha and LXRbeta. The mRNA expression of LXRs and their
target genes, including ABCA1, ABCG1 and ApoE, was significantly induced in
macrophages stimulated with squalene, resulting in removal of cholesterol from
the cells. Notably, squalene did not induce higher hepatic triacylglycerol levels
nor did it alter expression of sterol regulatory element-binding protein 1c
(SREBP-1c) and FAS in hepatocyte cells, primarily because of its upregulation of
Insig-2a, which delays nuclear translocation of SREBP-1c, a key hepatic lipogenic
transcription factor. CONCLUSION: Squalene has hypocholesterolemic effect through
the activation of LXRalpha and beta without inducing hepatic lipogenesis.
PMID- 28492977
TI - Chaperone-substrate interactions monitored via a robust TEM-1 beta-lactamase
fragment complementation assay.
AB - OBJECTIVE: To investigate the application of the TEM-1 beta-lactamase protein
fragment complementation assay (PCA) in detecting weak and unstable protein
protein interactions as typically observed during chaperone-assisted protein
folding in the periplasm of Escherichia coli. RESULTS: The TEM-1 beta-lactamase
PCA system effectively captured the interactions of three pairs of chaperones and
substrates. Moreover, the strength of the interactions can be quantitatively
analyzed by comparing different levels of penicillin resistance, and the assay
can be performed under 0.5% butanol, a stress condition thought to be
physiologically relevant. CONCLUSIONS: The beta-lactamase PCA system faithfully
reports chaperone-substrate interactions in the bacterial cell envelope, and
therefore this system has the potential to map the complex protein homeostasis
network under a fluctuating environment.
PMID- 28492978
TI - Seizure response to perampanel in drug-resistant epilepsy with gliomas: early
observations.
AB - Drug-resistant epilepsy (DRE) occurs commonly in gliomas, possibly due to a
shared mechanism of AMPA-activation involving both seizure activity and tumor
growth. We tested the AMPA-receptor blocker perampanel (PER) in patients with DRE
in low- and high-grade gliomas. Seizure response was defined as 50% drop in
seizure frequency or as seizure-freedom. Cognitive function was examined by
computerized test on cognitive speed (CTCS), which is sensitive to the type of
cognitive dysfunction associated with epilepsy and use of anticonvulsants.
Treatment policy included reduction of dose or discontinuation of one or more
concurrent AEDs, once a seizure-free response was observed. Twelve patients were
included patients, median age 41 years, 9 men versus 3 women and 6 months median
duration of follow-up. An objective seizure response (75%) was observed in 9
(75%) out of 12 patients: 50%-seizure response in 3, seizure-freedom in 6, which
is plainly more than seen with other types of DRE. Side-effects occurred in six
patients. Cognitive function as examined by CTCS improved in six out of eight
associated withlowering of concurrent AEDs. The final median dose of PER was 8 mg
(varying between 2 and 12 mg). These results of an objective seizure response in
9 (75%) out of 12 patients treated by PER in DRE may be interpreted as a
surrogate-marker of tumor response secondary to AMPA blockade, advancing
confirmation by MR imaging. These results warrant further study of PER on tumor
activity in gliomas.
PMID- 28492980
TI - [Haemostatic management in postpartum haemorrhage : Nationwide survey in
Germany].
AB - BACKGROUND: In order to ensure evidence-based haemostatic management of
postpartum haemorrhage (PPH, blood loss >500 ml) consistent with guidelines
appropriate structural conditions must be fulfilled regardless of different
levels (1-3) in perinatal care. The aim of the survey was to identify differences
in haemostatic management in PPH under consideration of the different levels of
perinatal care in Germany. MATERIALS AND METHODS: An electronic questionnaire
assessing the structural and therapeutic preconditions for haemostatic management
was sent to 533 anaesthesiology departments serving obstetric units. RESULTS: A
total of 156 (29 %) questionnaires returned from hospitals of all levels were
analysed. PPH occur in all and increase with higher level hospitals (level 1 <5
PPH/year vs. 3 >30 PPH/year). The percentage of PPH requiring red blood cell
(RBC) transfusion amounts to <25 % (all levels). A bleeding history (35 %, all
levels), laboratory coagulation tests (29 %, all levels) as well as viscoelastic
point-of-care coagulation tests (42 %, mainly level 3) are limited in their
availability. Blood loss is usually estimated (99 %, all levels), not measured.
Tranexamic acid (>80 %, all levels), fibrinogen (>60 %, all levels) and fresh
frozen plasma (FFP) (30 %, level 2a) are first line therapeutics. In level 2b and
3 FFP is a second line therapeutic. RBC transfusion is indicated at haemoglobin
<5-7 g/dl (57-69 %, all levels), while 15-29 % in level 3 did not base their
decision to transfuse RBC on haemoglobin only. CONCLUSIONS: Guideline-consistent
haemostatic management of PPH is provided in almost all hospitals independent of
the perinatal care level. Deviances from guidelines (measuring blood loss,
bleeding history of the patient) affect all levels of perinatal care in Germany.
PMID- 28492979
TI - Ethnic Identity, Acculturation, and 12-Month Psychiatric Service Utilization
Among Black and Hispanic Adults in the U.S.
AB - A cross-sectional study design was used to examine the associations of ethnic
identity, acculturation, and psychiatric service utilization among Wave 2
respondents of the National Epidemiologic Survey on Alcohol Related Conditions
with 12-month psychiatric disorders who self-identified as Black (6587, 19%) and
Hispanic (6359, 18%). Weighted multivariable regression analyses were conducted
to examine the relationships between ethnic identity, acculturation, and 12-month
psychiatric service utilization. Stronger ethnic identity was associated with
decreased odds of using psychiatric services among Black (AOR = 0.956; CI = 0.923
0.991) and Hispanic individuals (AOR = 0.967; CI = 0.945-0.990). Greater
acculturation was associated with an increased odds of psychiatric service
utilization for Hispanic individuals (AOR = 1.025; CI = 1.000-1.050). These
findings suggest that a sense of pride, belonging, and attachment to one's
racial/ethnic group and participating in ethnic behaviors is associated with
lower rates of participation in psychiatric services; alternatively, acquiring
key elements of the U.S. culture is associated with greater participation in
psychiatric services.
PMID- 28492981
TI - Evidence that Osteocytes in Autogenous Bone Fragments can Repair Disrupted
Canalicular Networks and Connect with Osteocytes in de novo Formed Bone on the
Fragment Surface.
AB - Autogenous bone fragments generated during surgery (e.g. implant site
preparation) accelerate bone formation by the release of a large variety of
growth factors from the extracellular matrix and the cells contained within.
Osteocytes, whether viable or apoptotic, within such fragments are able to
recruit osteoclasts to a site of bone remodelling. Here, using correlative
scanning electron microscopy, we provide compelling evidence that at one week
healing in the Sprague Dawley rat tibia, following surgery (and/or the placement
of a bone-anchored implant), autogenous bone fragments support bone formation on
their surface. Furthermore, osteocytes within the autogenous fragments are
frequently able to repair the disrupted canalicular networks and appear to
connect with osteocytes (or osteoblastic-osteocytes) in the de novo formed bone
on the surface of the fragment.
PMID- 28492982
TI - Adenosine A1 Receptors Play an Important Protective Role Against Cognitive
Impairment and Long-Term Potentiation Inhibition in a Pentylenetetrazol Mouse
Model of Epilepsy.
AB - Epilepsy is a complicated neurological disorder that occurs worldwide and
features several kinds of comorbidities in addition to recurrent seizures. One of
the most common comorbidities is cognitive impairment, which seriously affects
patients' quality of life. Through activating pre- and postsynaptic adenosine A1
receptors (A1Rs), adenosine has demonstrated anticonvulsant and neuroprotective
effects in many epileptic animal models. However, whether the neuroprotective
effect of A1Rs will protect cognition during epileptogenesis remains unknown.
Therefore, by using A1R knockout (KO) mice and establishing a pentylenetetrazole
(PTZ)-kindled model of epilepsy, the present study investigated A1Rs' influences
on memory and synaptic function. Morris water maze test results indicated that
A1R knockout exacerbated the memory impairment induced by PTZ kindling compared
with the wild-type group. To further study the synaptic function of epileptic
A1Rs KO mice, we recorded long-term potentiation (LTP) in the hippocampal CA3-CA1
pathway, and LTP was highly inhibited in kindled A1R KO mice compared with
kindled wild-type mice. To reveal the mechanisms underlying these effects,
neuronal loss, cell apoptosis, and relevant synaptic protein levels in
hippocampus were assessed. Epileptic A1R KO mice exhibited significant reductions
in neuronal cell survival in the CA1 region and a marked increase in the
activation of caspase-3 in the hippocampus compared with epileptic wild-type
mice. In addition, an obvious decrease in the PSD95 and BDNF expression levels of
epileptic A1R KO mice was observed 7 days after complete kindling. In conclusion,
these findings indicated that A1Rs play an important protective role against
cognitive impairment by reducing neuron loss and increasing BDNF and PSD95
levels. Activation of A1Rs during epileptogenesis might be beneficial to the
preservation of epileptic individuals' cognitive functions.
PMID- 28492983
TI - Target enrichment sequencing in cultivated peanut (Arachis hypogaea L.) using
probes designed from transcript sequences.
AB - Enabled by the next generation sequencing, target enrichment sequencing (TES) is
a powerful method to enrich genomic regions of interest and to identify sequence
variations. The objective of this study was to explore the feasibility of probe
design from transcript sequences for TES application in calling sequence variants
in peanut, an important allotetraploid crop with a large genome size. In this
study, we applied an in-solution hybridization method to enrich DNA sequences of
seven peanut genotypes. Our results showed that it is feasible to apply TES with
probes designed from transcript sequences in polyploid peanut. Using a set of
31,123 probes, a total of 5131 and 7521 genes were targeted in peanut A and B
genomes, respectively. For each genotype used in this study, the probe target
capture regions were efficiently covered with high depth. The average on-target
rate of sequencing reads was 42.47%, with a significant amount of off-target
reads coming from genomic regions homologous to target regions. In this study,
when given predefined genomic regions of interest and the same amount of
sequencing data, TES provided the highest coverage of target regions when
compared to whole genome sequencing, RNA sequencing, and genotyping by
sequencing. Single nucleotide polymorphism (SNP) calling and subsequent
validation revealed a high validation rate (85.71%) of homozygous SNPs, providing
valuable markers for peanut genotyping. This study demonstrated the success of
applying TES for SNP identification in peanut, which shall provide valuable
suggestions for TES application in other non-model species without a genome
reference available.
PMID- 28492984
TI - Comparative transcript profiling of fertile and sterile flower buds from multiple
allele-inherited male sterility in Chinese cabbage (Brassica campestris L. ssp.
pekinensis).
AB - We studied the underlying causes of multiple-allele-inherited male sterility in
Chinese cabbage (Brassica campestris L. ssp. pekinensis) by identifying
differentially expressed genes (DEGs) related to pollen sterility between fertile
and sterile flower buds. In this work, we verified the stages of sterility
microscopically and then performed transcriptome analysis of mRNA isolated from
fertile and sterile buds using Illumina HiSeq 2000 platform sequencing.
Approximately 80% of ~229 million high-quality paired-end reads were uniquely
mapped to the reference genome. In sterile buds, 699 genes were significantly up
regulated and 4096 genes were down-regulated. Among the DEGs, 28 pollen cell wall
related genes, 54 transcription factor genes, 45 phytohormone-related genes, 20
anther and pollen-related genes, 212 specifically expressed transcripts, and 417
DEGs located on linkage group A07 were identified. Six transcription factor genes
BrAMS, BrMS1, BrbHLH089, BrbHLH091, BrAtMYB103, and BrANAC025 were identified as
putative sterility-related genes. The weak auxin signal that is regulated by
BrABP1 may be one of the key factors causing pollen sterility observed here.
Moreover, several significantly enriched GO terms such as "cell wall organization
or biogenesis" (GO:0071554), "intrinsic to membrane" (GO:0031224), "integral to
membrane" (GO:0016021), "hydrolase activity, acting on ester bonds" (GO:0016788),
and one significantly enriched pathway "starch and sucrose metabolism" (ath00500)
were identified in this work. qRT-PCR, PCR, and in situ hybridization experiments
validated our RNA-seq transcriptome analysis as accurate and reliable. This study
will lay the foundation for elucidating the molecular mechanism(s) that underly
sterility and provide valuable information for studying multiple-allele-inherited
male sterility in the Chinese cabbage line 'AB01'.
PMID- 28492985
TI - Catheter ablation of paroxysmal atrial fibrillation: circumferential pulmonary
vein ablation: success rates with and without exclusion of areas adjacent to the
esophagus.
AB - BACKGROUND: Catheter ablation has become the first line of therapy in patients
with symptomatic, recurrent, drug-refractory paroxysmal atrial fibrillation.
Circumferential pulmonary vein ablation is still the standard approach in these
patients. The occurrence of an atrioesophageal fistula is a rare but life
threatening complication after such ablation procedures. This is due to the fact
that the esophagus does frequently have a very close anatomical relationship to
the left or right pulmonary vein ostia. The aim of our study was to evaluate
whether the exclusion of areas adjacent to the esophagus does have a significant
effect on the success rate after circumferential pulmonary vein ablation.
METHODS: Two hundred consecutive patients [121 men, 69 women; mean age 59.1 years
(SD +/- 11.3 years)] with symptomatic paroxysmal atrial fibrillation underwent a
circumferential pulmonary vein ablation procedure (using the CARTO- or the NAVX
system). In 100 patients, a complete circumferential pulmonary vein ablation was
attempted regardless of the anatomical relationship between the ablation sites
and the esophagus (group A). In the remaining 100 patients, the esophagus was
marked by a special EP catheter and areas adjacent to the esophagus were excluded
from the ablation procedure. After discharge, patients were scheduled for
repeated visits at the arrhythmia clinic at 1, 3, 6, 9, 12, 24 and 36 months
after the ablation procedure. RESULTS: The ablation procedure could be performed
as planned in all 200 patients. In group A, all pulmonary veins could be isolated
successfully in 88 out of 100 patients (88%). A mean number of 3.9 pulmonary
veins (SD +/- 0.37 PVs) were isolated per patient. The 12 cases of an incomplete
pulmonary vein isolation were due to poorly accessible pulmonary vein ostia. In
group B, all pulmonary veins could be isolated successfully in only 58 out of 100
patients (58%; P < 0.01). A mean number of 3.5 PVs (SD +/- 0.6 PVs) were isolated
per patient (P < 0.01). This was mostly due to a close anatomical relationship to
the esophagus. The ablation strategy had to be modified in 46/100 patients in
group B because of a close anatomical relationship between the right (n = 25) or
left (n = 21) pulmonary vein ostia and the esophagus. One year after the ablation
procedure, 87% of patients in group A (87/100) and 79% of patients in group B
(79/100) were free from an arrhythmia recurrence (P = 0.19). Three years after
catheter ablation, the success rate was 80% (no arrhythmia recurrence in 80 out
of 100 patients) in group A and 66% in group B (no arrhythmia recurrence in 66
out of 100 patients; P = 0.04). There were no major complications during long
term follow-up. CONCLUSIONS: The exclusion of areas adjacent to the esophagus
results in a markedly higher percentage of incompletely isolated pulmonary veins
after circumferential pulmonary vein ablation procedures. This results in a
significantly higher arrhythmia recurrence rate during long-term follow-up.
PMID- 28492986
TI - Biosynthesis and bioactivity of glucosinolates and their production in plant in
vitro cultures.
AB - MAIN CONCLUSION: Glucosinolates are biologically active compounds which are
involved in plant defense reaction. The use of plant in vitro cultures and
genetic engineering is a promising strategy for their sustainable production.
Glucosinolates are a class of secondary metabolites found mainly in Brassicaceae,
which contain nitrogen and sulfur in their structures. Glucosinolates are divided
into three groups depending on the amino acid from which they are biosynthesized.
Aliphatic glucosinolates are generally derived from leucine, valine, methionine,
isoleucine and alanine while indole and aromatic glucosinolates are derived from
tryptophan and phenylalanine or tyrosine, respectively. These compounds are
hydrolyzed by the enzyme myrosinase when plants are stressed by biotic and
abiotic factors, obtaining different degradation products. Glucosinolates and
their hydrolysis products play an important role in plant defense responses
against different types of stresses. In addition, these compounds have beneficial
effect on human health because they are strong antioxidants and they have potent
cardiovascular, antidiabetic, antimicrobial and antitumoral activities. Due to
all the properties described above, the demand for glucosinolates and their
hydrolysis products has enormously increased, and therefore, new strategies that
allow the production of these compounds to be improved are needed. The use of
plant in vitro cultures is emerging as a biotechnological strategy to obtain
glucosinolates and their derivatives. This work is focused on the biosynthesis of
glucosinolates and the bioactivity of these compounds in plants. In addition, a
detailed study on the strategies used to increase the production of several
glucosinolates, in particular those synthesized in Brassicaceae, using in vitro
plant cultures has been made. Special attention has been paid for increasing the
production of glucosinolates and their derivatives using metabolic engineering.
PMID- 28492987
TI - Copper Pollution Increases the Resistance of Soil Archaeal Community to Changes
in Water Regime.
AB - Increasing efforts have been devoted to exploring the impact of environmental
stresses on soil bacterial communities, but the work on the archaeal community is
seldom. Here, we constructed microcosm experiments to investigate the responses
of archaeal communities to the subsequent dry-rewetting (DW) disturbance in two
contrasting soils (fluvo-aquic and red soil) after 6 years of copper pollution.
Ten DW cycles were exerted on the two soils with different copper levels,
followed by a 6-week recovery period. In both soils, archaeal diversity (Shannon
index) in the high copper-level treatments increased over the incubation period,
and archaeal community structure changed remarkably as revealed by the non-metric
multidimensional scaling ordinations. In both soils, copper pollution altered the
response of dominant operational taxonomic units (OTUs) to the DW disturbance.
Throughout the incubation and recovery period, the resistance of archaeal
abundance to the DW disturbance was higher in the copper-polluted soils than
soils without pollution. Taken together, copper pollution altered the response of
soil archaeal diversity and community composition to the DW disturbance and
increased the resistance of the archaeal abundance. These findings have important
implications for understanding soil microbial responses to ongoing environmental
change.
PMID- 28492988
TI - The Threat of Antimicrobial Resistance on the Human Microbiome.
AB - Ubiquitous in nature, antimicrobial resistance (AMR) has existed long before the
golden age of antimicrobials. While antimicrobial agents are beneficial to combat
infection, their widespread use contributes to the increase in and emergence of
novel resistant microbes in virtually all environmental niches. The human
microbiome is an important reservoir of AMR with initial exposure occurring in
early life. Once seeded with AMR, commensal organisms may be key contributors to
the dissemination of resistance due to the interconnectedness of microbial
communities. When acquired by pathogens however, AMR becomes a serious public
health threat worldwide. Our ability to combat the threat of emerging resistance
relies on accurate AMR detection methods and the development of therapeutics that
function despite the presence of antimicrobial resistance.
PMID- 28492990
TI - Field-Scale Pattern of Denitrifying Microorganisms and N2O Emission Rates
Indicate a High Potential for Complete Denitrification in an Agriculturally Used
Organic Soil.
AB - More than 50% of all anthropogenic N2O emissions come from the soil. Drained
Histosols that are used for agricultural purposes are particularly potent sources
of denitrification due to higher stocks of organic matter and fertiliser
application. However, conditions that favour denitrification can vary
considerably across a field and change significantly throughout the year. Spatial
and temporal denitrifier dynamics were assessed in a drained, intensely managed
Histosol by focusing on the genetic nitrite and N2O reduction potential derived
from the abundance of nirK, nirS and nosZ genes. These data were correlated with
soil properties at two different points in time in 2013. N2O emissions were
measured every 2 weeks over three vegetation periods (2012-2014). Very low N2O
emission rates were measured throughout the entire period of investigation in
accordance with the geostatistical data that revealed an abundance of microbes
carrying the N2O reductase gene nosZ. This, along with neutral soil pH values, is
indicative of high microbial denitrification potential. While the distribution of
the microbial communities was strongly influenced by total organic carbon and
nitrogen pools in March, the spatial distribution pattern was not related to the
distribution of soil properties in October, when higher nutrient availability was
observed. Different nitrite reducer groups prevailed in spring and autumn. While
nirS, followed by nosZ and nirK, was most abundant in March, the latter was the
dominant nitrite reductase in October.
PMID- 28492991
TI - [Chronic kidney disease is not the same as chronic renal insufficiency].
PMID- 28492989
TI - Temporal Variations of Microbiota Associated with the Immature Stages of Two
Florida Culex Mosquito Vectors.
AB - Microbiota associated with mosquito vector populations impact several traits of
mosquitoes, including survival, reproduction, control, and immunity against
pathogens. The influence of seasonal variations and mosquito species on mosquito
gut microbiota is poorly understood. We sought to determine whether the mosquito
microbiota associated with immature stages of two congeners (Culex coronator and
Culex nigripalpus) differ temporally and between the two species. Using high
throughput 16S rRNA gene sequence analysis, we characterized bacterial and
archaeal communities found in the immature stages of the two Culex mosquito
species sampled over three seasons to compare the diversity of bacteria between
the two species. Beta diversity analyses of the larval microbiota sequences
revealed that the two Culex species differed significantly, both temporally
within each species and between the two species. Bacteria in Cx. coronator larvae
were dominated by Alphaproteobacteria, mainly associated with Roseoccocus and
unidentified species of Rhizobiales, and two unidentified species of
Cyanobacteria. In contrast, Cx. nigripalpus was dominated by Thorsellia anophelis
(Gammaproteobacteria), Clostridium, an unidentified species of Ruminococcacae
(Clostridiales), and additional unidentified species associated with
Erysipelotrichaceae (Erysipelotrichales), Bacteroidales, and Mollicutes. Results
of our study revealed both seasonal and interspecies differences in bacterial
community composition associated with the immature stages of Cx. coronator and
Cx. nigripalpus vector populations in Florida. These results have important
implications for our understanding of the underlying factors of variations in
disease transmission among seasons, susceptibility to various pesticides, and
other biotic factors, including the role of the microbiota on the spread of
invasive species. In addition, our results suggest close associations of certain
bacteria species with each of the two Culex species that will be further targeted
for their potential in the development of microbial-based control strategies.
PMID- 28492992
TI - [Choosing wisely recommendations in gastroenterology].
AB - The Choosing wisely initiative of the German Society of Internal Medicine
addresses procedures which are inadequately implemented (deficits in patient
care) as well as those which are performed too often but without proven benefits
for patients (misuse or overuse of health services). Based on their guidelines,
The German Society of Gastroenterology, Digestive and Metabolic Diseases has
identified such aspects and incorporated them into the respective
recommendations.
PMID- 28492993
TI - [Choosing wisely at the end of life : Recommendations of the German Society for
Palliative Medicine (DGP)].
AB - In addition to an overuse of unnecessary or no longer indicated diagnostic or
therapeutic procedures at the end of life in the sense of overtreatment, there is
often also a lack of therapeutic awareness in terms of a healthcare deficit, for
example concerning the recognition and treatment of symptoms and complex burden
of the disease. Sticking closely to the methodology of the German S3 "Palliative
Medicine" guideline, the Choosing wisely recommendations of the German Society
for Palliative Medicine address various examples of over- and underuse of
healthcare services and treatment at the end of life, and thus also mirror basic
principles of palliative medical care.
PMID- 28492994
TI - Metabolic characteristics and renal dysfunction in 65 patients with tophi prior
to gout.
AB - Tophi typically occur many years after uncontrolled gout. Therefore, their
development before gout remains unusual. Such patients might exhibit some
characteristic differences compared with typical tophaceous gout patients. In
this study, 65 tophaceous gout patients with tophi as the first sign of gout
(tophi-first group) were enrolled. Their clinical characteristics were compared
with those of 1421 patients whose tophi occurred after gout (tophi-after group).
Compared with the tophi-after group, the tophi-first group had a significantly
higher percentage of female patients and patients with elderly onset of disease
and a lower percentage of patients with a positive family history; these patients
had lower body mass indices, serum urate levels, and estimated glomerular
filtration rates (eGFRs). Female sex and negative family history were identified
as the principal determinants of tophi development before gout. The decreasing
eGFR among the tophi-first group was not due to the group per se but was a result
of older age, longer tophi duration, and hyperuricemia. The most common site of
initial tophi occurrence in both groups was the toe. In the tophi-first group,
the occurrence rates for initial tophi sites were significantly higher at the
finger but were lower at the ankle. The tophi-first group exhibited distinct
characteristics of age, gender, family history, BMI, serum urate levels, and
initial tophi site. This group had fewer comorbidities but similar renal
dysfunction compared with the tophi-after group. Thus, patients presenting with
tophi should be treated promptly, even if they have no history of gout symptoms.
PMID- 28492995
TI - General health status of long-term cervical cancer survivors after radiotherapy.
AB - PURPOSE: To evaluate the global health status of long-term cervical cancer
survivors (LCCS) who survived for more than 4 years after curative radiation
treatment (RT). PATIENTS AND METHODS: Medical records of 562 women treated with
RT in our institution between 2003 and 2010 were reviewed. Excluding 259 women
who died of disease or were lost to follow-up, disease status and late
morbidities were evaluated in 303 LCCS. Quality of life (QoL) was analyzed in 168
LCCS using a questionnaire from the European Organization for the Research and
Treatment of Cancer, and the results were compared with an age-matched healthy
Korean female population. RESULTS: Median follow-up was 6.8 years (range 4.1-12.5
years). There were 14 deaths (7 cancer specific) and 14 recurrences (5 local
recurrences and 9 distant metastases). The median time to recurrence was 6.0
years (range 4.1-8.2 years). Grade >=2 late toxicities were frequently observed
in the bladder (19%) and small/large intestine (15%). Multivariate analysis
revealed a higher rate of late toxicity in patients aged >=51 years at diagnosis
(small/large intestine: hazard ratio, HR, 2.5 [1.2-5.5]; bladder: HR 2.4 [1.3
4.5]; and bone: HR 4.3 [1.2-15.8]) than patients aged <51 years. Compared to the
general population, LCCS exhibited a significantly higher rate of body image
concerns, sexual dysfunction, lymphedema, and peripheral neuropathy. CONCLUSION:
New recurrences occurred in 5% of LCCS and grade >=2 treatment-related
morbidities were present in 33%. A significant proportion of LCCS also showed
decreased cervical-cancer-specific QoL. These results suggest the need for long
term surveillance and follow-up care for LCCS.
PMID- 28492996
TI - Patient Perspectives on Barriers to Surgical Care and the Impact of Mobile
Surgery in Ecuador.
AB - BACKGROUND: An estimated 5 billion people worldwide lack access to timely safe
surgical care (Gawande in Lancet 386(9993):523-525, 2015). A mere 6% of all
surgical procedures occur in the poorest countries where over a third of the
world's population lives (Meara et al. in Surgery 158(1):3-6, 2015). Mobile
surgical units like the Cinterandes Foundation endeavor to bring surgical care
directly to these communities who otherwise would lack access to safe surgery.
This study examines the barriers patients encounter in seeking surgical care in
rural communities of Ecuador and their impressions on how mobile surgery
addresses such barriers. METHODS: Open interviews were conducted with
Cinterandes' patients who had undergone an operation in the mobile surgical unit
between 06/25/2013 and 06/25/2014 (n = 101). Interviews were structured to
explore two main domains: (1) examining barriers patients have in accessing
surgery, (2) assessing patients' opinion of how mobile surgery helped in
overcoming such barriers. RESULTS: Patient inconvenience (70%), cost (21%), and
lack of trust in local hospitals (24%) were the main cited barriers to surgical
access. Increased patient convenience (53%), cheaper surgical care (34%), and
trust in Cinterandes (47%) were the main cited benefits to mobile surgery.
CONCLUSION: Mobile surgery provided by Cinterandes effectively overcomes many
barriers patients encounter when seeking surgical care in rural Ecuador:
decreased patient wait times, limited number of referrals to multiple locations,
and decreased cost. Partnering with local clinics within the communities and
bringing care much closer to patients' homes may provide a better patient
friendly health care delivery system for rural Ecuador.
PMID- 28492997
TI - Routine Contrast Esophagram in Anastomotic Leaks After Esophagectomy;
Methodological Issues on Diagnostic Value: Reply.
PMID- 28492998
TI - Enhanced Recovery After Surgery: Can We Rely on the Key Factors or Do We Need the
Bel Ensemble?
AB - BACKGROUND: The success of enhanced recovery (ERAS) pathways depends on the
actual application of the intended protocol (adherence), but its full
implementation remains challenging. In order to potentially streamline the
pathway, it is indispensable to know the impact of individual items and the
entire protocol on clinical outcomes. METHODS: Retrospective analysis including
all consecutive colorectal ERAS patients since implementation (May 2011) until
February 2014; demographics, adherence and outcomes were retrieved from a
prospectively maintained database. Primary outcome was the impact of individual
item and of the entire protocol on complications (overall and major) and length
of hospital stay. Statistical analysis included logistic multivariate regression
and adjustment for confounding factors. RESULTS: There were 328 patients with
complete data sets analyzed. A minimally invasive approach [odd ratio (OR) 0.62;
confidence interval (CI) 0.4-0.9] was significantly associated with less overall
complications. In contrast, the use of prophylactic nasogastric tubes (OR 3.18;
CI 1.4-7.4), prophylactic abdominal and pelvic drains (OR 1.96; 1.2-3.2) and
intraoperative thoracic epidural analgesia (OR 1.76; CI 1.3-2.4) were associated
with more overall complications. Minimal invasive approach was further associated
with reduced hospital stay (OR 0.5; CI 0.4-0.7) and less major complications (OR
0.58; CI 0.4-0.8). Higher adherence to the entire ERAS protocol was associated
with significantly less complications (P < 0.001) and shorter hospital stay (P <
0.001). CONCLUSIONS: Minimally invasive surgery was the single most important
component of the ERAS pathway while nasogastric tubes, drains and epidurals
should be avoided. Overall, increasing adherence with the protocol was associated
with better outcomes and should be the goal.
PMID- 28492999
TI - Physical activity improves cognition: possible explanations.
AB - Good cognitive abilities (CA) enable autonomy, improve social inclusion and act
preventively. Regular physical activity (PA) reduces the risk of developing
Alzheimer's disease (AD) and, at the same time, it reduces the decline of CA and
stimulates neurogenesis. So PA in connection with cognitive training, nutrition
and social interaction has a positive effect on general CA and the central
nervous system, the central executor, memory and attention, and reduces the
likelihood of developing dementia. Our objective was to examine which sort and
intensity of PA is preferred. We did a review, restricted only to human studies,
of transparent scientific articles and sample surveys carried out and published
in the period between 2001 and 2016 based on the keywords: age, aging, physical
activity, physical abilities, cognitive abilities, memory and Alzheimer's
disease. According to results CA and PA interact, as an increasing PA of only 10%
reduces the risk of dementia and AD significantly. However, there is a question
of appropriate intensity of exercise. Low-intensity aerobic exercise has a
positive effect on the visual spatial perception and attention, whereas moderate
PA has a positive impact on general CA, working memory and attention, verbal
memory and attention and vice versa. While the majority of experts recommends
vigorous or moderate exercise, many of them warn that higher intensity requires
more attention to PA and less to cognitive processes, particularly in terms of
reducing reactions, selective attention and flexibility to tasks. There is also a
further question what PA should be like. Although some experts believe that the
best combination is aerobic PA and exercises against resistance, it is not
entirely clear whether the improvement in CA is a result of cardiac vascular
fitness. On the other hand, for most elderly it is more suitable to perform an
alternative form (not anaerobic) of PA due to comorbidity and actual fragility.
We can conclude that PA has a positive effect on CA, but an appropriate intensity
and the type of exercise remain unsolved. For the relevant findings it is
absolutely necessary to have an interdisciplinary approach.
PMID- 28493000
TI - Serological and molecular tests for the diagnosis of Strongyloides stercoralis
infection in dogs.
AB - Strongyloides stercoralis can cause severe infection both in humans and dogs.
Coproparasitological examination has low sensitivity for the diagnosis of this
parasite; hence, different diagnostic techniques have been implemented. However,
serology and molecular methods have been assessed almost exclusively in humans.
In this study, two serologic assays and a real-time PCR (RT-PCR), routinely used
for the diagnosis of strongyloidiasis in humans, have been tested for the
diagnosis in dogs. Five dogs living in the same kennel in Bari, southern Italy,
were diagnosed with S. stercoralis infection by detection of larvae in fecal
samples processed by the Baermann method. Serum, fecal, and tissue (lungs,
scraping of intestinal tract) samples from the same dogs were tested with two
serologic assays (commercial ELISA, in-house IFAT) and with an in-house RT-PCR,
routinely used for diagnosis in humans. IFAT was positive in all serum samples,
ELISA in 3/7 (42.8%) samples. RT-PCR was positive in all pre-treatment fecal
samples, in all fecal debris, and in intestinal scraping (three samples from the
same deceased dog). The results suggest that IFAT and RT-PCR techniques routinely
used for S. stercoralis diagnosis in humans could be useful for the diagnosis of
the infection in dogs.
PMID- 28493001
TI - Study on the tolerance and adaptation of rats to Angiostrongylus cantonensis
infection.
AB - Angiostrongylus cantonensis (A. cantonensis) is the most common infectious agent
causing eosinophilic meningitis. As an important food-borne parasitic disease,
angiostrongyliasis cantonensis is an emerging infectious disease which brings
severe harm to central nerve system of human. Rat, one of the few permissive
hosts of A. cantonensis known to date, plays an indispensable role in the worm's
life cycle. However, the tolerance and adaptation of rat to A. cantonensis
infection is rarely understood. In this study, we infected rats with different
numbers the third stage larvae (L3) of A. cantonensis and explored their
tolerance through analysis on survival curve, neurological function score, and
detection of pathological damages in organs including the brain, lung, and heart
of the animals. Results indicated that rats' survival condition worsens, and body
weight dropped more significantly as more worms were used for infection. Death
appeared in groups infected with 80 and more A. cantonesnsis per rat. Morris
water maze revealed that the neurological function of rats damaged gradually with
increasing infection number of A. cantonensis larvae. When the number of infected
parasite exceeded 240 per animal, rats showed significant neurological
impairments. Collection of A. cantonensis from rat lung after 35 days of
infection implied an upper limit for worm entry, and the average length of worm
was inversely proportional to the infection amount, while the ratio between
female and male worms was positively related to the infection number. The degree
of pulmonary and cardiac inflammation was proportional to the infection number of
A. cantonensis. Meanwhile, there existed considerable amount of adult worms in
rat's right atrium and right ventricle, leading to a right heart myocardial
inflammation. The present study firstly reports the tolerance and adaptation of
rat, a permissive host of A. cantonensis to its infection, which will not only
provide accurate technical parameters for maintaining A. cantonensis life cycle
under laboratory conditions but also help unveil the underlying mechanism of the
distinct pathological outcomes in the permissive and non-permissive hosts with A.
cantonensis infection.
PMID- 28493002
TI - Dual-Prevention for UV-Induced Skin Damage: Incorporation of Melatonin-Loaded
Elastic Niosomes into Octyl Methoxycinnamate Pickering Emulsions.
AB - Incorporation of antioxidants into sunscreens is a logical approach, yet co
delivery of them with UV filters is a challenge. Here, we purposed a combination
therapy, in which the chemical UV filter, octyl methoxycinnamate, was accumulated
on upper skin while the antioxidant, melatonin, can penetrate deeper layers to
show its effects. Melatonin-loaded elastic niosomes and octyl methoxycinnamate
Pickering emulsion were prepared separately. Lyophilized elastic niosomes were
dispersed into the Pickering emulsion to prepare the proposed combination
formulation. The characterization studies of the formulations revealed that
elastic niosomes can be prepared with tunable nanometer sizes, whereas Pickering
emulsions can encapsulate the UV filter in micrometer-sized droplets. Melatonin
loaded elastic niosomes prepared with Tween80/Span80 mixture were 146 nm with a
PI of 0.438, and 58.42% entrapment efficiency was achieved. The mean diameter
size of the combination formulation was 27.8 MUm. Ex vivo permeation studies
revealed that 7.40% of octyl methoxycinnamate and 58% of melatonin were permeated
through the rat skin while 27.6% octyl methoxycinnamate and 37% of melatonin
accumulated in the skin after 24 h. Cell culture studies with real-time cell
analyzer showed that the proposed formulation consist of melatonin-loaded elastic
niosomes and octyl methoxycinnamate Pickering emulsion had no negative effect on
the cell proliferation and viability. According to alpha,alpha-diphenyl-beta
picrylhydrazyl free radical scavenging method, the proposed formulation showed as
high antioxidant activity as melatonin itself. It is concluded that the proposed
formulation would be a promising dual therapy for UV-induced skin damage with co
delivery strategy.
PMID- 28493003
TI - Bio-shielding In Situ Forming Gels (BSIFG) Loaded With Lipospheres for Depot
Injection of Quetiapine Fumarate: In Vitro and In Vivo Evaluation.
AB - Quetiapine fumarate (QF), an anti-schizophrenic drug, suffers from rapid
elimination and poor bioavailability due to extensive first-pass effect.
Intramuscularly (IM) injected lipospheres were designed to enhance the drug's
bioavailability and extend its release. A central composite design was applied to
optimize the liposphere preparation by a melt dispersion technique using
Compritol(r) 888 ATO or glyceryl tristearate as lipid component and polyvinyl
alcohol as surfactant. Lipospheres were evaluated for their particle size,
entrapment efficiency, and in vitro release. The optimized QF lipospheres were
prepared using a Compritol(r) 888 ATO fraction of 18.88% in the drug/lipid
mixture under a stirring rate of 3979 rpm. The optimized lipospheres were loaded
into a thermoresponsive in situ forming gel (TRIFG) and a liquid crystalline in
situ forming gel (LCIFG) to prevent in vivo degradation by lipases. The loaded
gels were re-evaluated for their in vitro release and injectability.
Bioavailability of QF from liposphere suspension and bio-shielding in situ gels
loaded with QF lipospheres were assessed in rabbits compared to drug suspension.
Results revealed that the AUC0-72 obtained from the liposphere-loaded TRIFG was
~3-fold higher than that obtained from the aqueous drug suspension indicating the
bio-shielding effect of Poloxamer(r) 407 gel to inhibit the biodegradation of the
lipospheres prolonging the residence of the drug in the muscle for higher
absorption. Our results propose that bio-shielding in situ Poloxamer(r) 407 gels
loaded with lipospheres is promising for the development of IM depot injection of
drugs having extensive first-pass metabolism and rapid elimination.
PMID- 28493004
TI - Efavirenz Dissolution Enhancement IV-Antisolvent Nanocrystallization by
Sonication, Physical Stability, and Dissolution.
AB - Efavirenz is a fundamental drug in the HIV therapy; however, it has a low
bioavailability due to low water solubility. Particle nanonization should enhance
its dissolution and therefore its bioavailability. Nanocrystallization is a
promising technique for preparing drug nanocrystals. A solution containing
efavirenz (EFV) and methanol was added to an aqueous solution of particle
stabilizers, under sonication. The adequate polymer stabilizer and its
concentration and drug load were evaluated. Particle size and zeta potential of
suspensions were measured. Nanosuspensions were freeze-dried and the resulting
powder was characterized by some techniques, with special attention to
dissolution. Particle size and zeta potential analysis showed that HMPC and PVP
were the most suitable polymers. All samples prepared with these stabilizers had
nanosized particles and proper zeta potential; however, sedimentation and
particle growth were detected with TurbiscanTM. Time-related destabilization
occurred when the lowest polymer concentration of 20% was used. SEM analysis of
the dried powder shows film formation for suspensions with 40% of polymer and
particle aggregation in samples with less polymer. Dissolution profiles of
samples were higher than EFV raw material, although the lower the polymer
concentration, the higher the dissolution.
PMID- 28493005
TI - Erratum to: Effects of aging on the relationship between cognitive demand and
step variability during dual-task walking.
PMID- 28493006
TI - Activity of Combined Antifungal Agents Against Multidrug-Resistant Candida
glabrata Strains.
AB - In this study, we evaluated the in vitro activity of echinocandins, azoles, and
amphotericin B alone and in combination against echinocandin/azole-sensitive and
echinocandin/azole-resistant Candida glabrata isolates. Susceptibility tests were
performed using the broth microdilution method in accordance with the Clinical
and Laboratory Standards Institute document M27-A3. The checkerboard method was
used to evaluate the fractional inhibitory concentration index of the
interactions. Cross-resistance was observed among echinocandins; 15% of the
isolates resistant to caspofungin were also resistant to anidulafungin and
micafungin. Synergistic activity was observed in 70% of resistant C. glabrata
when anidulafungin was combined with voriconazole or posaconazole. Higher (85%)
synergism was found in the combination of caspofungin and voriconazole. The
combinations of caspofungin with fluconazole, posaconazole and amphotericin B,
micafungin with fluconazole, posaconazole and voriconazole, and anidulafungin
with amphotericin B showed indifferent activities for the majority of the
isolates. Anidulafungin combined with fluconazole showed the same percentage of
synergism and indifference (45%). Antagonism was detected in 50% of isolates when
micafungin was combined with amphotericin B. Combinations of echinocandins and
antifungal azoles have great potential for in vivo assays which are required to
evaluate the efficacy of these combinations against multidrug-resistant C.
glabrata strains.
PMID- 28493007
TI - Gastrointestinal endoscopy in patients receiving novel direct oral
anticoagulants: results from the prospective Dresden NOAC registry.
AB - BACKGROUND: Patients receiving direct-acting, non-vitamin K oral anticoagulants
(NOAC) frequently undergo gastrointestinal endoscopies (GIE) but little is known
on the management and outcome of these interventions. METHODS: With use of data
from an ongoing, prospective, noninterventional registry of NOAC patients, the
management and outcome of GIE were evaluated with use of standard event
definitions. Patients undergoing GIE were categorized into two subgroups: (1)
scheduled GIE (scheduled appointment, no acute bleeding) and (2) unscheduled GIE
(unscheduled including management of acute gastrointestinal bleeding). The rates
of major bleeding complications, cardiovascular complications, and all-cause
death within 30 days after the procedure were evaluated. RESULTS: Between October
1, 2011, and March 31, 2015, 492 patients underwent a total of 713 GIE (44.5%
gastroscopies, 53.0% colonoscopies, 2.5% endoscopic retrograde
cholangiopancreatography procedures), with 70.0% being scheduled procedures and
30.0% being unscheduled procedures. Endoscopies were performed within 24 h after
the last NOAC intake in 45 of 713 cases (6.3%), between 24 and 48 h after the
last intake in 336 cases (47.1%), and after NOAC therapy interruption for more
than 48 h in 213 cases (29.9%). Heparin bridging therapy was used in 180 of 713
procedures (25.3%) and predominantly (170/180; 94.4%) in cases of NOAC therapy
interruption for longer than 72 h. Until day 30 after the procedure, the event
rates were 1.4% for cardiovascular events and 0.7% for major bleeding events.
CONCLUSION: Continuation or short-term interruption of NOAC therapy seems to be a
safe strategy for GIE. Heparin bridging therapy is predominantly used in cases of
prolonged NOAC therapy interruption.
PMID- 28493008
TI - Role of family history and tumor location on prognosis of patients with
colorectal cancer and synchronous metastases.
AB - BACKGROUND/AIMS: Family history of colorectal cancer and tumor location along
colon-rectum have been reported as prognostic factors. The aim of the current
study is to analyze the role of both on overall survival in a series of patients
with metastatic colorectal cancer with synchronous metastases. METHODS: A
retrospective mono-institutional analysis has been performed on patients, who
received chemotherapy from 2004 to 2008. A Cox proportional-hazards regression
was used to calculate hazard ratio (HR) for death, after adjustment for other
variables (tumor metastasectomy, number of organs involved with metastases,
number of anti-neoplastic drugs, age, sex, tumor grade, baseline CEA). RESULTS:
Two hundred and seven patients were included in the study. Only tumor
metastasectomy was related with a better overall survival (HR 4.995; P < 0.001),
whereas a positive family history was associated with a poor prognosis (HR 0.386;
P = 0.021). After exclusion of rectal tumors, the negative prognostic effect of a
positive family history appeared limited to patients with a left-sided colon
cancer (HR 0.183; P = 0.036). CONCLUSION: Family history for colorectal cancer in
a first-degree relative, and not tumor location, has a significant relationship
with the prognosis of patients with a colorectal cancer and synchronous
metastases.
PMID- 28493009
TI - Perivesical cystic duct of the gallbladder.
PMID- 28493010
TI - Multiple long bone cysts revealed by MRI in trichorhinophalangeal syndrome type
II predisposing to pathological fractures.
AB - Trichorhinophalangeal syndrome type II is a rare genetic disorder with the few
published case reports mainly reporting the radiographic skeletal manifestations.
There are no published imaging reports of long bone cysts involving multiple
bones in this condition. We report a unique case of bone cysts involving multiple
long bones detected with MRI in a patient with trichorhinophalangeal syndrome
type II complicated by a subsequent pathological fracture. It is possible that
the bone cysts are a previously undescribed feature of this syndrome; however,
the evidence is insufficient to establish a definite association. Chromosomal
abnormality identified in this patient is consistent with trichorhinophalangeal
syndrome type II with no unusual features. Although the nature of these bone
cysts is unclear, they are one of the causes of the known increased fracture risk
observed in this syndrome.
PMID- 28493011
TI - MRI of thoracic outlet syndrome in children.
AB - Thoracic outlet syndrome is caused by compression of the neurovascular bundle as
it passes from the upper thorax to the axilla. The neurovascular bundle can be
compressed by bony structures such as the first rib, cervical ribs or bone
tubercles, or from soft-tissue abnormalities like a fibrous band, muscle
hypertrophy or space-occupying lesion. Thoracic outlet syndrome commonly affects
young adults but can be seen in the pediatric age group, especially in older
children. Diagnosis is based on a holistic approach encompassing clinical
features, physical examination findings including those triggered by various
maneuvers, electromyography, nerve conduction studies and imaging. Imaging is
performed to confirm the diagnosis, exclude mimics and classify thoracic outlet
syndrome into neurogenic, arterial, venous or mixed causes. MRI and MR
angiography are useful in this process. A complete MRI examination for suspected
thoracic outlet syndrome should include the assessment of anatomy and any
abnormalities using routine sequences, vessel assessment with the arms in
adduction by MR angiography and assessment of dynamic compression of vessels with
abduction of the arms. The purpose of this paper is to describe the anatomy of
the thoracic outlet, causes of thoracic outlet syndrome, the MR imaging
techniques used in its diagnosis and the principles of image interpretation.
PMID- 28493012
TI - EEG Microstate Correlates of Fluid Intelligence and Response to Cognitive
Training.
AB - The neurobiological correlates of human fluid intelligence (Gf) remain elusive.
Here, we demonstrate that spatiotemporal dynamics of EEG activity correlate with
baseline measures of Gf and with its modulation by cognitive training. EEG
dynamics were assessed in 74 healthy participants by examination of fast
changing, recurring, topographically-defined electric patterns termed
"microstates", which characterize the electrophysiological activity of
distributed cortical networks. We find that the frequency of appearance of
specific brain topographies, spatially associated with visual (microstate B) and
executive control (microstate C) networks, respectively, is inversely related to
Gf scores. Moreover, changes in Gf scores with cognitive training are inversely
correlated with changes in microstate properties, indicating that the changes in
brain network dynamics are behaviorally relevant. Finally, we find that cognitive
training that increases Gf scores results in a posterior shift in the topography
of microstate C. These results highlight the role of fast-changing brain
electrical states in individual variability in Gf and in the response to
cognitive training.
PMID- 28493013
TI - The effects of Hurricane Sandy on trauma center admissions.
AB - BACKGROUND: Hurricane Sandy was a particularly unusual storm with regard to both
size and location of landfall. The storm landed in New Jersey, which is unusual
for a tropical storm of such scale, and created hazardous conditions which caused
injury to residents during the storm and in the months following. This study aims
to describe differences in trauma center admissions and patterns of injury during
this time period when compared to a period with no such storm. METHODS: Data were
collected for this study from patients who were admitted to the trauma center at
Morristown Medical Center during Hurricane Sandy or the ensuing cleanup efforts
(patients admitted between 29 October 2012 and 27 December 2012) as well as a
control group consisting of all patients admitted to the trauma center between 29
October 2013 and 27 December 2013. Patient information was collected to compare
the admissions of the trauma center during the period of the storm and cleanup to
the control period. RESULTS: A total of 419 cases were identified in the storm
and cleanup period. 427 were identified for the control. Striking injuries were
more common in the storm and cleanup group by 266.7% (p = 0.0107); cuts were more
common by 650.8% (p = 0.0044). Medical records indicate that many of these
injuries were caused by Hurricane Sandy. Self-inflicted injuries were more common
by 301.3% (p = 0.0294). There were no significant differences in the total number
of patients, mortality, or injury severity score between the two cohorts.
CONCLUSION: The data we have collected show that the conditions caused by
Hurricane Sandy and the following cleanup had a significant effect on injury
patterns, with more patients having been injured by being struck by falling or
thrown objects, cut while using tools, or causing self-inflicted injuries. These
changes, particularly during the cleanup period, are indicative of environmental
changes following the storm which increase these risks of injury.
PMID- 28493014
TI - Commentary on a case of body pushing and radiation exposure in screening of body
packing.
PMID- 28493015
TI - U.S. News Media Coverage of Pharmaceutical Pollution in the Aquatic Environment:
A Content Analysis of the Problems and Solutions Presented by Actors.
AB - Pharmaceutical pollution in the aquatic environment is an issue of concern that
has attracted attention by the news media. Understanding the factors that
contribute to media framing of pharmaceutical pollution may lead to a better
understanding of the management and governance of this issue, including why these
pollutants are generally unregulated at this time. This study conducted a content
analysis of 405 newspaper articles (81 had substantive information on the topic)
from 2007 to 2014, using the search terms "water" and "pharmaceuticals" in the
Chicago Tribune, Denver Post, Los Angeles Times, New York Daily News, New York
Times, USA Today, Wall Street Journal, and Washington Post. We sought to analyze
the factors that contributed to the news media presentation of pharmaceutical
pollution in the United States, including the presentation of the risks/safety
and solutions by various actors. We found that the primary issues in the news
media were uncertainty regarding public health and harm to the environment. The
primary solutions recommended within the news media were implementing additional
water treatment technologies, taking unused pharmaceuticals to predetermined
sites for disposal (take-back programs), and trash disposal of unused
pharmaceuticals. Water utilities and scientists presented improved water
treatment technology, government actors presented take-back programs, and
pharmaceutical representatives, while sparsely involved in the news media,
presented trash disposal as their primary solutions. To advance the understanding
of the management of pharmaceutical pollution, this article offers further
insight into the debate and potential solutions within the news media
presentation of this complex scientific topic.
PMID- 28493016
TI - Modelling the Risk Posed by the Zebra Mussel Dreissena polymorpha: Italy as a
Case Study.
AB - We generated a risk map to forecast the potential effects of the spreading of
zebra mussels Dreissena polymorpha across the Italian territory. We assessed the
invader's potential impact on rivers, lakes, watersheds and dams at a fine
grained scale and detected those more at risk that should be targeted with
appropriate monitoring. We developed a MaxEnt model and employed weighted overlay
analyses to detect the species' potential distribution and generate risk maps for
Italy. D. polymorpha has a greater probability of occurring at low to medium
altitudes in areas characterised by fluviatile deposits of major streams.
Northern and central Italy appear more at risk. Some hydroelectric power dams are
at high risk, while most dams for irrigation, drinkable water reservoirs and
other dam types are at medium to low risk. The lakes and rivers reaches
(representing likely expansion pathways) at medium-high or high risk mostly occur
in northern and central Italy. We highlight the importance of modelling potential
invasions on a country scale to achieve the sufficient resolution needed to
develop appropriate monitoring plans and prevent the invader's harmful effects.
Further high-resolution risk maps are needed for other regions partly or not yet
colonised by the zebra mussel.
PMID- 28493017
TI - Ecological Equivalence Assessment Methods: What Trade-Offs between
Operationality, Scientific Basis and Comprehensiveness?
AB - In many countries, biodiversity compensation is required to counterbalance
negative impacts of development projects on biodiversity by carrying out
ecological measures, called offset when the goal is to reach "no net loss" of
biodiversity. One main issue is to ensure that offset gains are equivalent to
impact-related losses. Ecological equivalence is assessed with ecological
equivalence assessment methods taking into account a range of key considerations
that we summarized as ecological, spatial, temporal, and uncertainty. When
equivalence assessment methods take into account all considerations, we call them
"comprehensive". Equivalence assessment methods should also aim to be science
based and operational, which is challenging. Many equivalence assessment methods
have been developed worldwide but none is fully satisfying. In the present study,
we examine 13 equivalence assessment methods in order to identify (i) their
general structure and (ii) the synergies and trade-offs between equivalence
assessment methods characteristics related to operationality, scientific-basis
and comprehensiveness (called "challenges" in his paper). We evaluate each
equivalence assessment methods on the basis of 12 criteria describing the level
of achievement of each challenge. We observe that all equivalence assessment
methods share a general structure, with possible improvements in the choice of
target biodiversity, the indicators used, the integration of landscape context
and the multipliers reflecting time lags and uncertainties. We show that no
equivalence assessment methods combines all challenges perfectly. There are trade
offs between and within the challenges: operationality tends to be favored while
scientific basis are integrated heterogeneously in equivalence assessment methods
development. One way of improving the challenges combination would be the use of
offset dedicated data-bases providing scientific feedbacks on previous offset
measures.
PMID- 28493018
TI - Emerging role of miRNA in attention deficit hyperactivity disorder: a systematic
review.
AB - Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric disorder
whose aetiology still remains elusive. Nevertheless, evidence supports a high
genetic contribution that interacts with environmental factors, also known to
modulate epigenetic processes. These epigenetic modulators are a class of non
coding RNAs, microRNAs (miRNAs), known as post-transcriptional regulators, which
have emerged as prospective players in neuropsychiatric disorders since they play
a role in brain development, synapse formation, and the fine-tuning of genes
underlying synaptic and memory formation. Here, we review the current literature
following a systematic search up until August 2016. The keywords used were
"ADHD", "attention deficit hyperactivity disorder", "attention hyperactivity" in
combination with "miRNA" or "microRNA". A total of 9 studies out of 34 met
inclusion criteria. The results provide preliminary information, shedding light
on two important aspects. First, it depicts that miRNAs modulate expression of
genes (BDNF, DAT1, HTR2C, HTR1B, SNAP-25) linked to ADHD aetiology. Dysregulation
of miRNAs affects regulatory mechanisms of aforementioned genes, which may affect
neurodevelopmental processes leading to alterations. Secondly, altered peripheral
miRNA levels are observed in both ADHD animal model and humans, suggesting a
notion of utilizing circulatory miRNA in disease diagnosis. Therefore,
deciphering the role of miRNAs in ADHD seems a promising step in understanding
its aetiology.
PMID- 28493019
TI - Surgical treatment of advanced penile cancer.
AB - PURPOSE: To evaluate the therapeutic effect of surgery in patients with advanced
penile cancer, who have a dismal prognosis. PATIENTS AND METHODS: Between
September 2007 and July 2015, we treated 12 patients with surgical therapy.
RESULTS: The median follow-up period for all the patients was 16 months (range 4
60 months). The outcome and concomitant symptoms were analyzed, and the survival
rates were calculated. Three of the patients are currently alive. The median
overall survival of the patients was 9 months (range 4-13 months). CONCLUSION:
The present results suggest that surgery is a valuable treatment option for
patients with advanced penile cancer. The prognosis of advanced penile cancer is
closely related to lymph node and distant metastases. Flap repair can solve the
problem of large area skin defect. Advanced penile cancer is difficult to treat
regardless of chemotherapy or radiotherapy, and surgery cannot prolong the lives
of patients. However, the dissection of lesions and repair of large area skin
defects can dramatically improve the quality of life of patients, especially
those with locally advanced disease without distant metastasis.
PMID- 28493020
TI - Development and validation of an analytical method based on liquid chromatography
tandem mass spectrometry detection for the simultaneous determination of 13
relevant wastewater-derived contaminants in lettuce.
AB - We present an analytical method developed and validated to study the potential
uptake of 13 selected drugs (ten pharmaceuticals, one illicit drug, and two
transformation products) into lettuce plants from contaminated water and soil.
Some of the selected drugs (i.e., cocaine, methadone, cis-diltiazem, valsartan,
and valsartan acid), which are commonly present in treated wastewater, were
investigated for the first time in plant tissues. The method is based on
ultrasonic solvent extraction with acetonitrile-methanol (1:1, v/v) and
subsequent automated extract cleanup and analysis by means of online solid-phase
extraction-liquid chromatography-tandem mass spectrometry. Optimum extraction
conditions were selected after evaluation of analyte recoveries with four
different extraction techniques (ultrasonic solvent extraction, solid-liquid
extraction, pressurized liquid extraction, and a "quick, easy, cheap, effective,
rugged, and safe" based method) and six different solvent mixtures. Furthermore,
two different solid-phase extraction cleanup sorbents were evaluated. The method
developed has high sensitivity (with limits of detection between 0.1 and 12.6 ng
per gram dry weight and limits of quantification between 0.5 and 42.0 ng per gram
dry weight), satisfactory accuracy (with analyte relative recoveries above 80%
for all analytes but acridone and oxcarbazepine), and good repeatability (with
relative standard deviations below 9% for all analytes). As part of the
validation procedure, the analytical method was applied to the analysis of
lettuce plants irrigated with water fortified with the selected compounds for the
entire growing period. The results obtained evidenced the transfer of all the
investigated drugs into lettuce leaves. Graphical Abstract ?.
PMID- 28493021
TI - Cobalt oxyhydroxide nanoflakes with intrinsic peroxidase catalytic activity and
their application to serum glucose detection.
AB - Cobalt oxyhydroxide (CoOOH) nanoflakes, an emerging type of two-dimensional
nanomaterial, show great potential for use in molecular detection. Previous
assays utilizing such materials have largely been based on their outstanding
fluorescence quenching ability and oxidizing power. Herein, we report the
intrinsic peroxidase-like activity of cobalt oxyhydroxide (CoOOH) nanoflakes, and
we show how this activity can be employed for glucose detection. We found that,
in the presence of hydrogen peroxide (H2O2), the nanoflakes accelerated the
conversion of peroxidase substrates such as 3,3',5,5'-tetramethylbenzidine (TMB)
into colored products. By combining the CoOOH nanoflakes with the biological
enzyme glucose oxidase (GOx), we developed a colorimetric method for the
detection of glucose within the concentration range 5.3-500 MUM. The proposed
method was applied to detect elevated blood glucose levels in diabetic patients,
and the intense color change induced by elevated glucose levels was found to be
readily apparent to the naked eye, proving the utility of our assay for point-of
care testing. Graphical abstract The intrinsic peroxidase-like activity of cobalt
oxyhydroxide (CoOOH) nanoflakes was exploited to enable the direct visualization
of elevated glucose levels in sera from diabetic patients.
PMID- 28493022
TI - In vitro anti-thrombotic and anti-coagulant properties of blacklip abalone
(Haliotis rubra) viscera hydrolysate.
AB - Abalone viscera contain sulphated polysaccharides with anti-thrombotic and anti
coagulant activities. In this study, a hydrolysate was prepared from blacklip
abalone (Haliotis rubra) viscera using papain and bromelain and fractionated
using ion exchange and size exclusion chromatography. Hydrolysates and fractions
were investigated for in vitro thrombin inhibition mediated through heparin
cofactor II (HCII) as well as anti-coagulant activity in plasma and whole blood.
On the basis of sulphated polysaccharide concentration, the hydrolysate inhibited
thrombin through HCII with an inhibitor concentration at 50% (IC50) of 16.5
MUg/mL compared with 2.1 MUg/mL for standard heparin. Fractionation concentrated
HCII-mediated thrombin inhibition down to an IC50 of 1.8 MUg/mL and improved anti
coagulant activities by significantly delaying clotting time. This study
confirmed the presence of anti-thrombotic and anti-coagulant molecules in
blacklip abalone viscera and demonstrated that these activities can be enriched
with a simple chromatography regime. Blacklip abalone viscera warrant further
investigation as a source of nutraceutical or functional food ingredients.
Graphical abstract Schematic showing preparation of bioactive extracts and
fractions from blacklip abalone.
PMID- 28493023
TI - The paramedian supracerebellar infratentorial approach.
AB - BACKGROUND: Lesions of the superior cerebellar surface, pineal region, lateral
and dorsal midbrain and mesial temporal lobe are challenging to treat and often
require neurosurgical intervention. METHODS: The paramedian variation of the
supracerebellar infratentorial approach utilizes the downward slope of the
cerebellum to facilitate exposure and the lower density of cerebellar bridging
veins away from the midline decreases the need to sacrifice larger venous
channels. We also discuss our experiences with the approach, and some of the
drawbacks and nuances that we have encountered as it has evolved over the years.
CONCLUSIONS: This approach is versatile and effective and the authors' surgical
approach of choice for resecting these challenging lesions.
PMID- 28493024
TI - De novo vertebral artery dissecting aneurysm after internal trapping of the
contralateral vertebral artery.
AB - We present the case of a de novo vertebral artery dissecting aneurysm (VADA)
after endovascular trapping of a ruptured VADA on the contralateral side. The
first ruptured VADA involved the posterior inferior cerebellar artery, which was
successfully treated by endovascular internal trapping using a stent. A follow-up
study at 3 months revealed a de novo VADA on the contralateral side. The second
VADA was successfully embolized using coils while normal arterial flow in the
vertebral artery was preserved using a stent. Increased hemodynamic stress may
cause the development of a de novo VADA on the contralateral side.
PMID- 28493025
TI - CRNDE Expression Positively Correlates with EGFR Activation and Modulates Glioma
Cell Growth.
AB - BACKGROUND: The long non-coding RNA CRNDE has emerged as an important regulator
in carcinogenesis and cancer progression. While CRNDE has previously been found
to be the most highly upregulated lncRNA in glioma, detailed information on its
roles in regulating cancer cell growth remains limited. OBJECTIVE: In the present
study, we aimed at exploring the functional roles and underlying mechanisms of
CRNDE in glioma. METHODS: We applied microarray data analysis to determine the
prognostic significance of CRNDE in glioma patients and its correlation with
epidermal growth factor receptor (EGFR) activation. EGFR inhibition was used to
confirm the role of EGFR in regulating CRNDE expression. Functional studies were
performed upon CRNDE silencing to explore its role in gliomagenesis. RESULTS: We
confirm that CRNDE acts as an oncogene that is highly up-regulated in glioma, and
high CRNDE expression correlates with poor prognosis in glioma patients. We
further demonstrate that the expression of CRNDE correlates with EGFR activation.
EGF and EGFR tyrosine kinase inhibitor (TKI) enhance and block the up-regulation
of CRNDE expression, respectively, suggesting that EGFR signaling may positively
regulate CRNDE expression. Functional assays show that CRNDE depletion inhibits
glioma cell growth both in vitro and in vivo, and is associated with induced
cellular apoptosis with decreased Bcl2/Bax ratio. CONCLUSIONS: Our findings
suggest that the aberrant expression of CRNDE may be mediated by activated EGFR
signaling and play significant roles in gliomagenesis.
PMID- 28493026
TI - Structural and functional characterization of a novel immunomodulatory
glycoprotein isolated from ajowan (Trachyspermum ammi L.).
AB - Ajowan (Trachyspermum ammi L.) spice has been used in food preparations and also
as a traditional medicine in Ayurveda. Although a number of pharmacological
activities have been attributed to ajowan, its role in immunomodulation is not
known. The main objective of the present study is to examine the macromolecular
immunomodulatory components. Macrophage activation was studied by nitric oxide
(NO) release, phagocytosis and secretion of pro-inflammatory cytokines as the
markers. Ethanol precipitate (fractional) of ajowan aqueous extract was subjected
to conventional chromatography (Q Sepharose followed by Bio-Gel P-100). One of
the proteins (30.7 kDa; ajowan glycoprotein or Agp) showed effective mitogenic
activity towards splenocytes. Agp is a O-linked glycoprotein with the glycans
contributing to one-third of the molecular mass. It has a high content of
glutamic acid, serine, aspartic acid and proline whereas galactose (45.7%),
arabinose (34.5%), glucose (7%), mannose (5%) and xylose (4%) are the constituent
sugars. Secondary structure analysis indicated that Agp contains 79% alpha
helices and 21% random coil. Internal sequencing of the tryptic peptides did not
show homology with the existing proteins in the database (BLAST). Agp at 1 MUg/mL
induced proliferation of B-cell enriched murine splenocytes and activated
macrophages in releasing NO and promoted phagocytosis (p < 0.01). RAW 264.7 cells
produced pro-inflammatory cytokines (IL-12, TNF-alpha and IFN-gamma) at 1 MUg/mL
Agp (p < 0.01). Deproteinized Agp (dpAgp) failed to elicit activation of murine
immune cells, whereas deglycosylated Agp (20 kDa; dgAgp) showed compromised
efficiency. This is the first report of an immunomodulatory protein from ajowan.
PMID- 28493027
TI - Clinicopathological characteristics of thyroid cancer in the federal state of
Salzburg.
AB - OBJECTIVE: The aim of our investigation was to evaluate the clinicopathological
characteristics and mutation patterns in newly diagnosed cases of thyroid cancer
in the federal state of Salzburg, Austria, in the year 2013. METHODS: The medical
records of all patients newly diagnosed with thyroid cancer in 2013 in the
federal state of Salzburg were retrospectively reviewed. The clinicopathological
characteristics and mutations of thyroid cancers were analyzed. RESULTS: 63
patients (mean age: 51.0 years, range: 21-81 years; female 75%, male 25%) were
identified. 53 patients had papillary (12 follicular variant), 4 patients
follicular (1 oxyphilic variant), 3 patients medullary, and 3 patients anaplastic
thyroid cancer. T1 tumors were found in 34 patients (pT1a, 20 patients; pT1b, 14
patients), T2 tumors in 10 patients, T3 tumors in 16 patients, and T4 tumors in 3
patients. Lymph node involvement was seen in 15 patients and metastatic disease
in 1 patient. Mutations of BRAF (B-type Raf kinase) were detected in 23 and
mutation of NRAS (Neuroblastoma RAS Viral Oncogene Homolog) in 2 papillary
thyroid cancers. No concomitant mutations of BRAF and NRAS were found.
CONCLUSION: Females accounted for 75% of the patients with newly diagnosed
thyroid cancer and the incidence peaked at a younger age than in males. Papillary
thyroid cancer was the most frequent tumor type, accounting for 84% of the cases.
A high frequency of T1 tumors and cancers with no lymph node involvement was
found. Males had a higher proportion of large tumors and more aggressive forms of
thyroid cancer than females. Mutations (mostly of BRAF) were found in 47% of the
cases. Neither mutations of KRAS (Kirsten rat sarcoma viral oncogene homologue)
nor concomitant mutations of BRAF and NRAS were found.
PMID- 28493028
TI - Every cloud has a silver lining.
PMID- 28493030
TI - Ambulatory blood pressure response to a bout of HIIT in metabolic syndrome
patients.
AB - PURPOSE: The effectiveness of exercise to lower blood pressure may depend on the
type and intensity of exercise. We study the short-term (i.e., 14-h) effects of a
bout of high-intensity aerobic interval training (HIIT) on blood pressure in
metabolic syndrome (MetS) patients. METHODS: Nineteen MetS patients (55.2 +/- 7.3
years, 6 women) entered the study. Eight of them were normotensive and eleven
hypertensive according to MetS threshold (>=130 mmHg for SBP and/or >=85 mmHg for
DBP). In the morning of 3 separated days, they underwent a cycling exercise bout
of HIIT (>90% of maximal heart rate, ~85% VO2max), or a bout of isocaloric
moderate-intensity continuous training (MICT; ~70% of maximal heart rate, ~60%
VO2max), or a control no-exercise trial (REST). After exercise, ambulatory blood
pressure (ABP; 14 h) was monitored, while subjects continued their habitual daily
activities wearing a wrist-band activity monitor. RESULTS: No ABP differences
were found for normotensive subjects. In hypertensive subjects, systolic ABP was
reduced by 6.1 +/- 2.2 mmHg after HIIT compared to MICT and REST (130.8 +/- 3.9
vs. 137.4 +/- 5.1 and 136.4 +/- 3.8 mmHg, respectively; p < 0.05). However,
diastolic ABP was similar in all three trials (77.2 +/- 2.6 vs. 78.0 +/- 2.6 and
78.9 +/- 2.8 mmHg, respectively). Motion analysis revealed no differences among
trials during the 14-h. CONCLUSION: This study suggests that the blood pressure
reducing effect of a bout of exercise is influence by the intensity of exercise.
A HIIT exercise bout is superior to an equivalent bout of continuous exercise
when used as a non-pharmacological aid in the treatment of hypertension in MetS.
PMID- 28493029
TI - Age and sex differences in human skeletal muscle fibrosis markers and
transforming growth factor-beta signaling.
AB - PURPOSE: The aim of the study was to determine whether higher fibrosis markers in
skeletal muscle of older adults are accompanied by increased expression of
components of the canonical TGF-beta signal transduction pathway. METHODS:
Fourteen healthy young (21-35 years; 9 males and 5 females) and seventeen older
(55-75 years; 9 males and 8 females) participants underwent vastus lateralis
biopsies to determine intramuscular mRNA and protein expression of fibrogenic
markers and TGF-beta signaling molecules related to TGF-beta1 and myostatin.
RESULTS: Expression of mRNA encoding the pro-fibrotic factors; axin 2, collagen
III, beta-catenin and fibronectin, were all significantly higher (all p < 0.05)
in the older participants (350, 170, 298, and 641%, respectively). Furthermore,
axin 2 and beta-catenin mRNA were significantly higher in older females than
older males (p < 0.05). Gene expression of ActRIIB, myostatin, and TGF-beta1 were
higher in older adults compared to younger adults (all p < 0.05). There was,
however, no difference in the total protein content of myostatin, myoD or
myogenin (all p > 0.05), whereas Smad3 protein phosphorylation was 48% lower (p <
0.05) in muscle from older adults. CONCLUSIONS: Increased abundance of mRNA of
fibrotic markers was observed in muscle from older adults and was partly
accompanied by altered abundance of pro-fibrotic ligands in a sex specific
manner.
PMID- 28493031
TI - FOXC1 overexpression is a marker of poor response to anthracycline-based adjuvant
chemotherapy in sporadic triple-negative breast cancer.
AB - PURPOSE: Because of its aggressive characteristics and poor prognosis, triple
negative breast cancer (TNBC) has become a hot topic in cancer research.
Chemotherapy is currently the only treatment for patients with TNBC. The
transcription factor FOXC1 has been associated with TNBC prognosis, but little is
known about its effect on chemosensitivity. The aim of this study was to
investigate the effects of FOXC1 on chemosensitivity. METHODS: A case-control
study was performed on 25 TNBC patients who experienced relapse and/or
metastasis. Another 25 patients without relapse or metastasis were randomly
selected as controls. Medical records were reviewed for relevant information, and
immunohistochemistry was performed to measure FOXC1 levels. The Kaplan-Meier
method and Cox analysis were used to analyze differences in disease-free survival
(DFS) and overall survival (OS). The correlation of FOXC1 expression with
chemosensitivity was analyzed. Data were analyzed using SPSS 21.0 software, and a
P value <0.05 was considered to be statistically significant. RESULTS: In 15 of
22 case patients, FOXC1 was overexpressed, whereas only 8 control patients
exhibited FOXC1 overexpression (P < 0.05). FOXC1 expression had no correlation
with pathological indicators. An anthracycline-based regimen was administered to
21 study patients and 23 control patients. FOXC1 expression was significantly
associated with a worse DFS (HR 2.62, 95% CI 1.05-6.50, P = 0.038) but presented
no correlation with OS (HR 2.53, 95% CI 0.76-8.40, P = 0.131) among these 44
patients. CONCLUSIONS: This study shows that FOXC1 is correlated with
chemosensitivity to anthracycline and could be used as an indicator of
chemosensitivity in sporadic TNBC.
PMID- 28493032
TI - Is there any predictor for hypersensitivity reactions in gynecologic cancer
patients treated with paclitaxel-based therapy?
AB - PURPOSE: Recently, generic drugs of paclitaxel have been commonly used mainly by
economic reasons; however, predictive factors for toxicities are not fully
determined. Hypersensitivity reaction (HSR) is one of the most important adverse
events in the paclitaxel-based therapy, and sometimes leads to lethal condition.
The aim of the study was to identify predictors for HSR in patients treated with
paclitaxel-based regimens. METHODS: All the patients treated with chemotherapy
including paclitaxel at our hospital between 1998 and 2013 were retrospectively
evaluated. Clinicopathological factors of the patients that developed HSR and
those without HSR were compared, and predictive factors for HSR were identified.
RESULTS: Among 414 patients enrolled in the study, 26 patients (6.3%) developed
HSR. Multivariate analyses showed that younger age (odds ratio 6.31), a history
of allergy (odds ratio 3.79), and short-course premedication (odds ratio 14.1)
were identified as predictive factors for HSR. There was no significant
difference in the incidence of HSR between original paclitaxel and generic drug.
The incidence of HSR was higher as the number of these predictors was
accumulated. CONCLUSIONS: Three factors were identified as predictive factors for
HSR: younger age, a history of allergy, and short-course premedication.
Accumulation of these factors increased the incidence of HSR; however, the use of
generic drug was not associated HSR in gynecologic cancer patients.
PMID- 28493033
TI - Is there a genetic anticipation in breast and/or ovarian cancer families with the
germline c.3481_3491del11 mutation?
AB - The aim of the current analysis is to evaluate any differences of breast or
ovarian cancer age at diagnosis between mothers and daughters carrying the
c.3481_3491del11 mutation in the BRCA1 gene. A study cohort of 38 women carrying
the c.3481_3491del11 mutation and affected by first breast or ovarian cancer who
reported a first breast or ovarian cancer in their mother carrying the
c.3481_3491del11 mutation, was identified in 37 different families including
members with breast and/or ovarian cancer at the Oncology Institute of Lorraine.
Twelve mothers underwent genetic testing. Twenty-five pairs of the 38 mothers
daughters pairs with c.3481_3491del11 mutation were affected by breast cancer and
13 pairs by ovarian cancer. Clinical and genetic data were collected from medical
files and family pedigrees. Analyses were conducted for each cancer type. We
investigated an early breast cancer detection effect due to early screening
programs and also an increased breast tumor aggression. Since major improvements
in breast cancer clinical management and imaging techniques appeared after 1980,
we compared the age at breast cancer diagnosis and the age at death in mothers
and daughters before and after 1980, first, in the group of women including
mothers and daughters taken together and then in mothers and daughters
separately. The mean age at breast cancer diagnosis was 45.28 +/- 10.27 years in
mothers and 39.80 +/- 7.79 years in daughters (p = 0.026). The difference of age
at ovarian cancer diagnosis in mother-daughter pairs was 8.62 +/- 12.76 years (p
= 0.032). When considering the group of women including mothers and daughters
taken together, no significant difference of age at breast cancer diagnosis was
found between women affected before 1980 and those affected after 1980 (p =
0.577). However, the age at death increased in these women after 1980 (p =
0.026). Comparison of age at breast cancer diagnosis in mothers and daughters
separately, showed that daughters were affected at an earlier age after 1980 (p =
0.002). Daughters had a poor prognosis and died earlier than mothers after 1980.
Our results may have reflected genetic anticipation in c.3481_3491del11 mutation
breast and ovarian cancer families. In order to confirm our findings, a larger
cohort would provide more precision to the difference of ages at breast or
ovarian cancer diagnosis between mothers and daughters and more powerful
statistical analyses. Increased aggression in daughters' tumors compared to those
of mothers could be also considered as a parameter of genetic anticipation.
Complete information on tumor profile and proliferation would allow us to study
genetic anticipation by comparing the tumor phenotypes between mothers and
daughters in the future.
PMID- 28493034
TI - [A Japanese in Marburg : Excerpts from the Memories - Jiden - of the Japanese
Bacteriologist Taichi Kitashima (1870-1956)].
AB - The heart of this article is the transmission of selected chapters from the
Japanese bacteriologist Taichi Kitashima's (1870-1956) autobiographical memoirs
(in Japanese, Jiden) published in 1955, in which Kitashima reports on his stay in
Marburg in a very personal and subjective way. Like other Japanese physicians of
his generation, Kitashima spent several years in Germany in order to work with
the serum researcher Emil von Behring and continued his education there. The
contact came through Kitashima's teacher Shibasaburo Kitasato, who had worked
with Behring in Berlin on questions of immunology. The memoir gives insight into
Behring's laboratory work and his relation to his "subordinates". The editors
investigate to what extent Kitashima's assessment, made from a distance of fifty
years, of his stay in Germany as "wasted time" was accurate, given the advantages
that arose from having been part of a vibrant European scientific community,
including encounters in the Pasteur Institute in Paris, and why he cultivated his
contacts with Germany and the Behring family during National Socialism.
PMID- 28493035
TI - Overlapping MALDI-Mass Spectrometry Imaging for In-Parallel MS and MS/MS Data
Acquisition without Sacrificing Spatial Resolution.
AB - Metabolomics experiments require chemical identifications, often through MS/MS
analysis. In mass spectrometry imaging (MSI), this necessitates running several
serial tissue sections or using a multiplex data acquisition method. We have
previously developed a multiplex MSI method to obtain MS and MS/MS data in a
single experiment to acquire more chemical information in less data acquisition
time. In this method, each raster step is composed of several spiral steps and
each spiral step is used for a separate scan event (e.g., MS or MS/MS). One main
limitation of this method is the loss of spatial resolution as the number of
spiral steps increases, limiting its applicability for high-spatial resolution
MSI. In this work, we demonstrate multiplex MS imaging is possible without
sacrificing spatial resolution by the use of overlapping spiral steps, instead of
spatially separated spiral steps as used in the previous work. Significant
amounts of matrix and analytes are still left after multiple spectral
acquisitions, especially with nanoparticle matrices, so that high quality MS and
MS/MS data can be obtained on virtually the same tissue spot. This method was
then applied to visualize metabolites and acquire their MS/MS spectra in maize
leaf cross-sections at 10 MUm spatial resolution. Graphical Abstract ?.
PMID- 28493036
TI - Life-cycle of Amblyomma oblongoguttatum (Acari: Ixodidae) under laboratory
conditions.
AB - This study evaluated for the first time the life cycle of Amblyomma
oblongoguttatum in the laboratory. For this purpose, larvae and nymphs were
exposed to Gallus gallus (chicks), Rattus norvegicus (wistar rat), Calomys
callosus (vesper mouse), Oryctolagus cuniculus (domestic rabbit), Cavia porcellus
(guinea pig), and Didelphis albiventris (white-eared opossum). Nymphs were
exposed to G. gallus, C. callosus, C. porcellus, O. cuniculus, R. norvegicus, and
Nectomys squamipes (water rat). Adult ticks were exposed to domestic dogs. The
life-cycle of A. oblongoguttatum in the laboratory could be completed in an
average period of 188 days, considering prefeeding periods of 25 days for each of
the parasitic stages. Under laboratory conditions, none of the host species was
highly suitable for A. oblongoguttatum larvae, since the recovery rates of
engorged larvae were always <15%, or most of the times <=5%. Similar results were
obtained for nymphs, with recovery rates of engorged nymphs always <6%. Our
results, coupled with literature data, suggest that small mammals, especially
small rodents, do not have an important role in the life-cycle of A.
oblongoguttatum under field conditions. Domestic dogs showed to be highly
suitable for the adult stage of A. oblongoguttatum, in agreement with literature
data that have appointed dogs as important hosts for the adult stage of A.
oblongoguttatum in South America.
PMID- 28493037
TI - Toxicity of vegetable oils to the coconut mite Aceria guerreronis and selectivity
against the predator Neoseiulus baraki.
AB - The coconut mite, Aceria guerreronis (Acari: Eriophyidae), is a major tropical
pest of coconut. Here, we assessed the chemical profiles and the potential use of
babassu, degummed soybean, and coconut oils to control A. guerreronis as well as
their side-effects on the predatory mite Neoseiulus baraki (Acari: Phytoseiidae),
a key natural enemy of the coconut mite. Babassu and coconut oils had similar
fatty acids chemical profiles. All vegetable oils showed toxicity to A.
guerreronis; degummed soybean oil exhibited the highest toxicity (LC50 = 0.15
uL/cm2). Although all oils were less toxic to N. baraki, their potential to
attract/repel this predatory mite differed. Whereas N. baraki females were
unresponsive to coconut oil at both concentrations (i.e., LC50 and LC99 estimated
for A. guerreronis), irrespective of exposure period (i.e., 1 or 24 h), the
babassu oil repelled the predator, independent of exposure period, when applied
at its LC99 (1.48 uL/cm2). Intriguingly, this oil also exhibited attractiveness
to N. baraki 24 h after exposure when applied at its LC50 (0.26 uL/cm2). A
similar attractiveness pattern was recorded 24 h after N. baraki was exposed to
degummed soybean oil at both concentrations tested (LC50 = 0.15 uL/cm2; LC99 =
1.39 uL/cm2). However, N. baraki was repelled by degummed soybean oil at its LC50
after 1 h of exposure. Therefore, the present study demonstrated that all the
vegetable oils used here had higher toxicity to the coconut mite and considerable
selectivity to the predator N. baraki, indicating they are promising tools that
can potentially be included in management programs to control A. guerreronis in
commercial coconut plantations.
PMID- 28493038
TI - Perioperative implications of thoracic decortications: a retrospective cohort
study.
AB - PURPOSE: An increasing number of thoracic decortications have been performed in
Manitoba, from five in 2007 to 45 in 2014. The primary objective of this study
was to define the epidemiology of decortications in Manitoba. The secondary
objective was to compare patients who underwent decortication due to primary
infectious vs non-infectious etiology with respect to their perioperative
outcomes. METHODS: Data for this cohort study were extracted from consecutive
charts of all adult patients who underwent a decortication in Manitoba from 2007
2014 inclusive. RESULTS: One hundred ninety-two patients underwent a
decortication. The most frequent disease processes resulting in a decortication
were pneumonia (60%), trauma (13%), malignancy (8%), and procedural complications
(5%). The number of decortications due to complications of pneumonia rose at the
greatest rate, from three cases in 2007 to 29 cases in 2014. Performing a
decortication for an infectious vs a non-infectious etiology was associated with
a higher rate of the composite postoperative outcome of myocardial infarction,
acute kidney injury, need of vasopressors for > 12 hr, and mechanical ventilation
for > 48 hr (44.4% vs 24.2%, respectively; relative risk, 1.83; 95% confidence
interval, 1.1 to 2.9; P = 0.01). CONCLUSION: There has been a ninefold increase
in decortications over an eight-year period. Potential causes include an increase
in the incidence of pneumonia, increased organism virulence, host changes, and
changes in practice patterns. Patients undergoing decortication for infectious
causes had an increased risk for adverse perioperative outcomes.
Anesthesiologists need to be aware of the high perioperative morbidity of these
patients and the potential need for postoperative admission to an intensive care
unit.
PMID- 28493039
TI - Complications after surgical treatment of femoral neck fractures in men with
alcohol dependence syndrome: retrospective register analysis of 154 cases.
AB - PURPOSE: One-third of hip fractures occur in men. The causes underlying hip
fractures in men differ from those in women and include alcohol abuse. This
retrospective register study evaluated the trends and results associated with
different surgical treatment methods for nondisplaced and displaced femoral neck
fractures in male patients with alcohol dependence syndrome. METHODS: Men with
hip fractures were identified from a local district hospital database. Alcohol
dependence syndrome was identified as a diagnosis in medical records. RESULTS:
For displaced fractures, implant survival after total hip arthroplasty was
significantly lower compared to hemiarthroplasty. For nondisplaced fractures,
implant survival of cannulated screws was significantly lower compared to sliding
hip screws. Overall patient survival for males with alcohol dependence syndrome
with hip fracture was 62% at 1 year and 49% at 2 years. Patient survival in this
population did not differ between displaced and nondisplaced fractures or among
different surgical methods. CONCLUSION: Patients with alcoholism who had
documented evidence of alcohol dependence syndrome represented nearly half of
patients <70 years old with low-energy hip fracture. In patients with
nondisplaced femoral neck fractures, stability of the internal fixation appeared
to play a major role in implant survival; sliding hip screws should be considered
over multiple cannulated screws. In patients with displaced fracture, total hip
arthroplasty was associated with a significantly higher risk of complications
leading to revision compared to hemiarthoplasty. LEVEL OF EVIDENCE: Prognostic
Level III.
PMID- 28493040
TI - Stability of capsule closure and postoperative anterior knee pain after medial
parapatellar approach in TKA.
AB - PURPOSE: Anterior knee pain after total knee arthroplasty (TKA) remains a widely
discussed postoperative complication. In contrast to sports traumatology, the
role of the dissected medial patellofemoral ligament (MPFL) using a medial
parapatellar approach in TKA has not been discussed so far. In the present study,
it was hypothesized that the attempted repair of the MPFL in TKA by simple
closure of the joint capsule may not be successful in some cases, causing
anterior knee pain. Furthermore, it was hypothesized, that the success of repair
might be influenced by femoral component rotation. METHODS: Forty patients
received their TKA in a ligament-balanced and forty patients in a conventional
measured-resection technique. After implantation of the TKA using a medial
parapatellar approach, two titan clips were attached on both sides of the capsule
incision. 3 days and 3 months after surgery, the dehiscence of the two clips was
measured on skyline patella radiographs; additionally patellar tilt, shift, the
Knee Society Score and the Feller Score were obtained. RESULTS: 48 patients
showed an increase of capsule dehiscence. Patients with a capsule dehiscence of
more than 4 mm showed significantly less improvement in the Feller score 3 months
postoperatively than patients with a capsule dehiscence <=4 mm. Regarding the
radiological measurements and the clinical outcome, no significant difference
between the ligament-balanced and the measured-resection group was found.
CONCLUSIONS: The present results suggest that the successful repair of the MPFL
after using a medial parapatellar approach in TKA could reduce the high rate of
postoperative anterior knee pain. Furthermore, the appearance of capsule
dehiscence and anterior knee pain does not seem to be dependent on the used
operative technique.
PMID- 28493041
TI - The sinus tarsi approach in displaced intra-articular calcaneal fractures.
AB - INTRODUCTION: Although the extended lateral approach is typically considered the
gold standard of treatment for intra-articular calcaneal fractures, a limited
lateral approach may be a good alternative in select cases. METHODS: Forty-seven
consecutive patients with intra-articular calcaneal fractures treated using the
sinus tarsi approach between March 2010 and April 2015 were retrospectively
reviewed. The functional outcomes [including arc range of motion, Visual Analog
Scale (VAS) score, and the American Orthopedic Foot and Ankle Society
ankle/hindfoot (AOFAS) score], bony outcomes (bony restoration and bony union),
and complications were evaluated. RESULTS: The mean one-year postoperative VAS
and AOFAS scores were 0.54 (range 0-3.0), and 94.0 (range 80-100), respectively.
The VAS and AOFAS scores were correlated with the degree of reduction of the
posterior facet joint and the amount of Bohler angle restoration. Bony union was
achieved in every case. The mean union time was 3.2 months (range 3-4 months).
There were no major soft tissue complications. Three cases of minor soft tissue
complications healed with no need for subsequent procedures. Painful hardware at
the posterior calcaneal tuberosity was the most common complication, which
occurred in seven cases. CONCLUSIONS: The sinus tarsi approach may be a good
option to treat intra-articular calcaneal fractures in select cases (Sanders type
II and III) while preventing the major soft tissue complications of the extended
lateral approach. Level of evidence IV.
PMID- 28493042
TI - On the stochastic evolution of finite populations.
AB - This work is a systematic study of discrete Markov chains that are used to
describe the evolution of a two-types population. Motivated by results valid for
the well-known Moran (M) and Wright-Fisher (WF) processes, we define a general
class of Markov chains models which we term the Kimura class. It comprises the
majority of the models used in population genetics, and we show that many well
known results valid for M and WF processes are still valid in this class. In all
Kimura processes, a mutant gene will either fixate or become extinct, and we
present a necessary and sufficient condition for such processes to have the
probability of fixation strictly increasing in the initial frequency of mutants.
This condition implies that there are WF processes with decreasing fixation
probability-in contradistinction to M processes which always have strictly
increasing fixation probability. As a by-product, we show that an increasing
fixation probability defines uniquely an M or WF process which realises it, and
that any fixation probability with no state having trivial fixation can be
realised by at least some WF process. These results are extended to a subclass of
processes that are suitable for describing time-inhomogeneous dynamics. We also
discuss the traditional identification of frequency dependent fitnesses and pay
offs, extensively used in evolutionary game theory, the role of weak selection
when the population is finite, and the relations between jumps in evolutionary
processes and frequency dependent fitnesses.
PMID- 28493043
TI - Revisional Surgery After Failed Laparoscopic Sleeve Gastrectomy: Retrospective
Analysis of Causes, Results, and Technical Considerations.
AB - BACKGROUND: A failed laparoscopic sleeve gastrectomy (LSG) presents a challenging
problem for bariatric surgeons. The aim of this study was to evaluate the
indications, treatment strategies, and surgical outcomes of patients who
underwent a revisional surgery after a failed LSG. METHODS: This retrospective
study included the outcomes of 32 patients who required a revisional surgery from
a series of 500 primary LSGs. The patients' demographic data, indications for
revisional surgery, perioperative complications, and postoperative outcomes were
recorded. RESULTS: A total of 500 patients underwent primary LSGs during the
study period, and 32 of these patients were subjected to revisional bariatric
surgery after a failed LSG. Weight regain, poor weight loss, and gastroesophageal
reflux disease (GERD) were the most common causes of revision. A revisional LSG
(r-LSG) was performed in 23 patients, while 9 patients received a revisional
laparoscopic Roux-en-Y gastric bypass (r-LRYGB). There were complete sleeve pouch
dilations in 10 patients. A residual fundus and antrum dilation was detected in 5
and 8 patients, respectively. The r-LRYGB procedure was performed for GERD
related symptoms in 6 patients and 3 other patients underwent r-LRYGB due to the
intake of high-caloric foods. The mean operative time, length of hospital stay,
and complication rates of revisional surgeries were significantly higher than the
total cohort. CONCLUSIONS: Although r-LSG and r-LRYGB seem to be safe and
effective treatment options after a failed LSG, revisional procedures were
associated with an increased complication rate. Attention to technical details of
the primary LSG may reduce the revision requirements.
PMID- 28493044
TI - Postoperative upgrading of prostate cancer in men >=75 years: a propensity score
matched analysis.
AB - PURPOSE: Gleason score upgrading should be considered when indicating surgery in
prostate cancer (PCa) patients. In elderly patients, definitive treatment of low
risk PCa must be weighed with the risks of overtreatment. Our aim was to evaluate
rates of Gleason score upgrading in patients >=75 years undergoing radical
prostatectomy (RP) for localized PCa and to identify predictors associated with
upgrading. METHODS: 3296 patients undergoing RP were retrospectively evaluated
and categorized into age groups: <70 years (n = 2971) vs. >=75 years (n = 325).
We analyzed prostate-specific antigen (PSA), biopsy counts, Gleason score,
pathologic T- and N-stage, and surgical margin. Propensity score matching was
performed to compare rates of up- and downgrading on surgical specimen using the
new five-tier pathologic grading system. Logistic regression was used to identify
independent predictors of upgrading. RESULTS: Preoperatively, patients >=75 years
had higher PSA (8.8 vs. 7.3 ng/mL) and lower proportion of grade group 1 (Gleason
score 6) at biopsy (29.2 vs. 47.9%; both p < 0.001) compared to patients <70
years. At RP, patients >=75 years were more likely to have extraprostatic disease
(50 vs. 30%) and lower rates of grade group 1 (14.1 vs. 34.8%; both p < 0.001).
Postoperative downgrading was similar (15.1 vs. 19.5%). However, patients >=75
years had higher rates of postoperative upgrading (46.6 vs. 27.9%; p < 0.001).
Age >=75 years, higher PSA levels at RP, and an increased number of positive
biopsy cores were associated with upgrading. CONCLUSIONS: Patients >=75 years not
only demonstrated higher rates of advanced disease but more frequent upgrading on
RP specimen. Age >=75 years, higher PSA levels at RP, and an increased number of
positive biopsy cores were predictive for upgrading. The increased risk of
upgrading should be taken into consideration when discussing optimal treatment
for this specific cohort.
PMID- 28493045
TI - Impact of treatment regimen on acute care use during and after adjuvant
chemotherapy for early-stage breast cancer.
AB - PURPOSE: The Oncology Care Model was developed, in part, to reduce acute care use
during the 6 months after chemotherapy initiation. However, little is known about
the impact of chemotherapy regimen on acute care needs, or about later acute
care. We sought to assess acute care use over 2 years in patients receiving four
contemporary adjuvant chemotherapy regimens for breast cancer. METHODS:
Administrative claims data from a large U.S. commercial insurance database
(OptumLabs Data Warehouse) were used to retrospectively identify women with early
stage breast cancer who received adjuvant doxorubicin-cyclophosphamide (AC), AC
followed or preceded by docetaxel or paclitaxel (AC-T), AC concurrent with
docetaxel or paclitaxel (TAC), or docetaxel-cyclophosphamide (TC) between 2008
and 2014. Rates of hospitalizations and emergency department (ED) visits that did
not lead to hospitalizations were compared during four sequential 6-month periods
among recipients of these four regimens using negative binomial regression (TC =
reference). RESULTS: We identified 8621 eligible patients, 87.2% younger than 65.
Over 6 months, 11.9% were hospitalized and 17.1% had ED visits. Over 24 months,
17.9% were hospitalized and 28.3% visited the ED. Adjusted rates of
hospitalizations/100 patients were significantly higher in AC-T and TAC compared
to TC recipients in the first 6 months (14.9, 21.9, and 11.3, respectively, p <
0.001). There were no hospitalization rate differences among regimens later. ED
visit rates did not differ significantly by regimen during any 6-month period.
CONCLUSION: Higher rates of hospitalizations in recipients of AC-T and TAC were
restricted to the chemotherapy administration period, and did not persist
afterwards.
PMID- 28493046
TI - Trastuzumab uptake and its relation to efficacy in an animal model of HER2
positive breast cancer brain metastasis.
AB - PURPOSE: The extent to which efficacy of the HER2 antibody Trastuzumab in brain
metastases is limited by access of antibody to brain lesions remains a question
of significant clinical importance. We investigated the uptake and distribution
of trastuzumab in brain and mammary fat pad grafts of HER2-positive breast cancer
to evaluate the relationship of these parameters to the anti-tumor activity of
trastuzumab and trastuzumab emtansine (T-DM1). METHODS: Mouse transgenic breast
tumor cells expressing human HER2 (Fo2-1282 or Fo5) were used to establish
intracranial and orthotopic tumors. Tumor uptake and tissue distribution of
systemically administered 89Zr-trastuzumab or muMAb 4D5 (murine parent of
trastuzumab) were measured by PET and ELISA. Efficacy of muMAb 4D5, the PI3K/mTOR
inhibitor GNE-317, and T-DM1 was also assessed. RESULTS: 89Zr-trastuzumab and
muMAb 4D5 exhibited robust uptake into Fo2-1282 brain tumors, but not normal
brains. Uptake into brain grafts was similar to mammary grafts. Despite this,
muMAb 4D5 was less efficacious in brain grafts. Co-administration of muMAb 4D5
and GNE-317, a brain-penetrant PI3K/mTOR inhibitor, provided longer survival in
mice with brain lesions than either agent alone. Moreover, T-DM1 increased
survival in the Fo5 brain metastasis model. CONCLUSIONS: In models of HER2
positive breast cancer brain metastasis, trastuzumab efficacy does not appear to
be limited by access to intracranial tumors. Anti-tumor activity improved with
the addition of a brain-penetrant PI3K/mTOR inhibitor, suggesting that combining
targeted therapies is a more effective strategy for treating HER2-positive breast
cancer brain metastases. Survival was also extended in mice with Fo5 brain
lesions treated with T-DM1.
PMID- 28493047
TI - Effects of CPAP in patients with obstructive apnoea: is the presence of allergic
rhinitis relevant?
AB - PURPOSE: The aim of the study is to compare the effects of continuous positive
airway pressure (CPAP) on the nasal cavities of patients with obstructive sleep
apnoea (OSA) and with or without allergic rhinitis (AR/nonAR). METHODS: This
paper is a prospective, longitudinal study. Thirty-four consecutive CPAP
treatment-adherent patients with OSA (17 AR and 17 nonAR) were evaluated before
and 2 months after treatment, by means of clinical (otorhinolaryngological
symptoms, daytime sleepiness, overall and rhinoconjunctivitis-specific quality of
life), anatomical (otorhinolaryngological examination), functional (auditory
function, tubal function, nasal airflow, and mucociliary clearance), and
biological variables (nasal cytology). No humidifier or anti-allergy medicines
were used during treatment. RESULTS: Before treatment, patients with AR presented
a higher score, compared to nonAR in rhinitis symptoms (4.82 +/- 2.53 vs. 0.93 +/
1.02, p = 0.000), otologic symptoms (2.06 +/- 1.95 vs. 0.44 +/- 0.72, p =
0.004), cutaneous/ocular symptoms (2.12 +/- 2.17 vs. 0.65 +/- 1.17, p = 0.052),
immunoglobulin E (181.82 +/- 126.09 vs. 66.13 +/- 97.97, p = 0.004), and nasal
neutrophils (14.42 +/- 31.94 vs. 0.16 +/- 0.39, p = 0.031). After treatment,
nonAR and AR groups improved in daytime sleepiness (11.53 +/- 4.60 vs. 7.53 +/-
2.87, p = 0.000 and 13.76 +/- 4.93 vs. 7.53 +/- 4.41, p = 0.001) respectively and
increased nasal neutrophil (0.16 +/- 0.39 vs. 5.78 +/- 9.43, p = 0.001 and 14.42
+/- 31.94 vs. 79.47 +/- 202.08, p = 0.035). The symptoms and quality of life
improved in patients with AR. NonAR patients, significantly increase nasal
dryness (1.65 +/- 1.27 vs. 0.00, p = 0.002) and mucociliary clearance times
(38.59 +/- 24.90 vs. 26.82 +/- 23.18, p = 0.016). CONCLUSIONS: CPAP produces
inflammation with increased nasal neutrophil levels in AR and nonAR patients.
Nevertheless, patients with AR observed an improvement in nasal symptoms and
quality of life, whereas in patients without AR, a relevant worsening of nasal
dryness and mucociliary transport was observed.
PMID- 28493048
TI - A Novel omega3-Desaturase in the Deep Sea Giant Tubeworm Riftia pachyptila.
AB - One paradox of the trophic biochemistry of the deep sea giant tubeworm Riftia
pachyptila, endemic to hydrothermal vent sites and nourished by polyunsaturated
fatty acid (PUFA) deficiency chemolitoautotrophic sulfide-oxidizing bacteria, is
the source of their PUFAs. Biosynthesis of PUFA starts with two precursors C18:2n
6 and C18:3n-3, which cannot be biosynthesized by most animals due to lack of
omega6- and omega3-desaturase; thus, C18:2n-6 and C18:3n-3 are generally
essential fatty acids for animals. Here, we characterized a gene derived from the
R. pachyptila located by hydrothermal vent, which encoded a novel omega3
desaturase (Rp3Fad). The gene was identified by searching the R. pachyptila
transcriptome database using known omega3-desaturases, and its predicted protein
showed 37-45% identical to omega3-desaturases of fungus and microalgae, and only
31% identitical to nematode Caenorhabditis elegans omega3-desaturase. Expression
in yeast Saccharomyces cerevisiae showed that the Rp3Fad could desaturate C18:2n
6 and C18:3n-6 into C18:3n-3 and C18:4n-3, respectively, displaying a Delta15
activity similar to plant omega3-desaturase, but it showed no activity towards
C20 n-6 PUFA substrates, differing from the well-characterized C. elegans omega3
desaturases. Delta5, Delta6, Delta8, and Delta12 activity were also tested,
resulting in no corresponding production. The function of omega3-desaturase
identified in R. pachyptila could produce C18:3n - 3 used in synthesis of n - 3
series PUFAs, suggesting an adaption to PUFA deficiency environment in deep sea
hydrothermal vent.
PMID- 28493049
TI - Identification and Differential Expression of Biomineralization Genes in the
Mantle of Pearl Oyster Pinctada fucata.
AB - A series of proteins are involved in shell formation of the pearl oyster Pinctada
fucata, but the involved mechanisms and the relative expression levels of these
proteins have not been elucidated. In this study, we sequenced and characterized
the transcriptome of P. fucata mantle tissue. A total of 100,679 unique
transcripts were assembled, 43687 Unigenes were annotated, and 48654 CDSs were
determined. Of these, GO annotated 16353 Unigenes, COG defined 11585 unigenes
into 25 categories, and KEGG sorted 25053 unigenes into 258 pathways. In total,
67 biomineralization-related genes were identified, of which 23 genes were newly
described in P. fucata. These genes included ones that expressed shell matrix
proteins, regulatory factors, and uncharacterized genes. Differential expression
of these 67 genes and 9 other biomineralization-related genes was confirmed using
qPCR. Of the 8 nacreous layer-related genes, MSI60 (774.00) was expressed at a
much higher level than the others. KRMP2-4 and MSI31 were the most highly
expressed of the 13 prismatic layer-related genes and KRMP2 was expressed at
nearly 10000 times of the level of the 18S gene. For genes related to both
layers, shematrin 2 (3977.84), nacrein (2404.75), PFMG 10 (2113.93), and PFMG 4
(1015.89) were highly expressed, and ferritin-like protein (877.54) and PFMG 8
(516.48) were highly expressed among the 16 undefined genes. The expression
levels of regulation factors were generally low, and the highest level was 324.09
(EF-hand) and the lowest occurred in the BMP and wnt families. The expression
levels of the prismatic matrix proteins were much higher than those of nacreous
ones, consistent with a thicker prismatic layer. MSI60 and nacrein are likely the
main components of the nacreous layer, and KRMP2-4, MSI31, shematrin 2, and PFMG
10 gene products are the main components of the prismatic layer. This is the
first report of transient expression levels of a large number of
biomineralization-related genes at the same time in mantle tissue of P. fucata.
These findings provide a novel perspective to understand the molecular mechanisms
of shell formation and will be beneficial to genetic improvement of P. fucata for
the production of high-quality pearls as well.
PMID- 28493051
TI - Erratum to: Genetic analysis of four European huchen (Hucho hucho Linnaeus, 1758)
broodstocks from Poland, Germany, Slovakia, and Ukraine: implication for
conservation.
PMID- 28493052
TI - Development of a colorimetric reverse transcription loop-mediated isothermal
amplification assay for the detection of Mirafiori lettuce big-vein virus.
AB - An RT-LAMP assay was developed to detect Mirafiori lettuce big vein virus
(MiLBVV) and was compared with DAS-ELISA and RT-PCR. All primers were designed on
the basis of the coat protein gene of the virus. In addition, a novel
immunocapture (IC) RT-LAMP assay for rapid and easy detection of MiLBVV was
developed, and factors such as safety, simplicity, cost, user-friendliness and
safety were compared with those of DAS-ELISA, RT-PCR and RT-LAMP assays. Compared
with DAS-ELISA and RT-PCR, RT-LAMP and IC-RT-LAMP had higher sensitivity (100
fold) but similar specificity, with the advantage of a shorter assay time and no
need for RNA extraction (in IC-RT-LAMP). As RT-LAMP requires only very basic
instruments and the results can be obtained by visual inspection (using
GeneFinderTM dye), this technique provides a simple and reliable tool for
laboratory research.
PMID- 28493050
TI - Fasudil ameliorates endothelial dysfunction in streptozotocin-induced diabetic
rats: a possible role of Rho kinase.
AB - Endothelial dysfunction is a major contributor to the pathogenesis of vascular
disease in diabetes mellitus and RhoA/Rho-kinase (ROCK) system appears to play a
crucial role in this setting. The present study was conducted to investigate the
effect of the selective ROCK inhibitor, fasudil, on diabetes-related endothelial
dysfunction and elucidated its underlying mechanism(s). Diabetes was induced by a
single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg), and fasudil
(5 mg/kg per day) was orally administered for 8 weeks. Our results showed that
fasudil administration attenuated the increased activity/expression of ROCK
(627.5 +/- 27 vs. 247.8 +/- 19.1) and the NADPH oxidase subunits, NOX2 and
p47phox, in diabetic rat aorta. Fasudil could reduce the elevated tumor necrosis
factor (TNF)-alpha (70.2 +/- 14.1 vs. 25.3 +/- 5.2) and transforming growth
factor (TGF-beta) levels and restored the deficit in antioxidant level of the
diabetic aorta. Additionally, fasudil markedly improved the endothelial
dysfunction in the diabetic aorta (73.8 +/- 8.1 vs. 47.42 +/- 8.69) and corrected
the dysregulated endothelial nitric oxide (eNOS) expression. In conclusion, the
present study demonstrates that fasudil effectively ameliorates the endothelial
dysfunction in STZ-induced diabetic rats through inhibition of the Rho/ROCK
pathway and thereby reducing the TNF-alpha-mediated NADPH oxidase activation.
PMID- 28493053
TI - Regulation of cathepsin D activity by the FTLD protein progranulin.
PMID- 28493054
TI - The Dynamics of a SEIR-SIRC Antigenic Drift Influenza Model.
AB - We consider the dynamics of an influenza model with antigenic drift mechanism.
Antigenic drift is an antigen mutation on the skin surface of the influenza virus
that do not produce a new virus strain. The mutation produces the same virus but
with slightly different antigens that cannot be recognized by the immune
receptors formed by the previous infection. There are some type of influenza that
involve the interaction between two populations such as human and animal. In this
paper, we construct an influenza model with antigenic drift mechanism on the
human population that has interaction with the animal population. The animal
population is assumed to follow the SEIR epidemic model. Our model is motivated
by the fact that some of the influenza cases in human come from the animal such
as the swine and the avian. The transmission parameter that shows number of
contact between the susceptible human and the infectious animals are important to
study. The parameter plays an important role to detect the cycle of infection of
the disease. The other important parameters are the seasonality degree, which
shows the pathogen appearance and disappearance via annual migration, and the
infection rate on the human population. We employ the bifurcation theory to
analyze the behavior of the system and to detect the cycle of infection types
when the parameters values are varied.
PMID- 28493055
TI - A Patient-Specific Anisotropic Diffusion Model for Brain Tumour Spread.
AB - Gliomas are primary brain tumours arising from the glial cells of the nervous
system. The diffuse nature of spread, coupled with proximity to critical brain
structures, makes treatment a challenge. Pathological analysis confirms that the
extent of glioma spread exceeds the extent of the grossly visible mass, seen on
conventional magnetic resonance imaging (MRI) scans. Gliomas show faster spread
along white matter tracts than in grey matter, leading to irregular patterns of
spread. We propose a mathematical model based on Diffusion Tensor Imaging, a new
MRI imaging technique that offers a methodology to delineate the major white
matter tracts in the brain. We apply the anisotropic diffusion model of Painter
and Hillen (J Thoer Biol 323:25-39, 2013) to data from 10 patients with gliomas.
Moreover, we compare the anisotropic model to the state-of-the-art Proliferation
Infiltration (PI) model of Swanson et al. (Cell Prolif 33:317-329, 2000). We find
that the anisotropic model offers a slight improvement over the standard PI
model. For tumours with low anisotropy, the predictions of the two models are
virtually identical, but for patients whose tumours show higher anisotropy, the
results differ. We also suggest using the data from the contralateral hemisphere
to further improve the model fit. Finally, we discuss the potential use of this
model in clinical treatment planning.
PMID- 28493056
TI - Non-Vitamin K Oral Anticoagulants for Stroke Prevention in Special Populations
with Atrial Fibrillation.
AB - Atrial fibrillation (AF) is associated with an increased risk of ischemic stroke
or systemic embolism compared with normal sinus rhythm. These strokes may
efficiently be prevented in patients with risk factors using oral anticoagulant
therapy, with either vitamin K antagonists (VKAs) or non-vitamin K antagonist
oral anticoagulants (NOACs) (i.e., direct thrombin inhibitors or direct factor Xa
inhibitors). Owing to their specific risk profiles, some AF populations may have
increased risks of both thromboembolic and bleeding events. These AF patients may
be denied oral anticoagulants, whilst evidence shows that the absolute benefits
of oral anticoagulants are greatest in patients at highest risk. NOACs are an
alternative to VKAs to prevent stroke in patients with "non-valvular AF", and
NOACs may offer a greater net clinical benefit compared with VKAs, particularly
in these high-risk patients. Physicians have to learn how to use these drugs
optimally in specific settings. We review concrete clinical scenarios for which
practical answers are currently proposed for use of NOACs based on available
evidence for patients with kidney disease, elderly patients, women, patients with
diabetes, patients with low or high body weight, and those with valve disease.
PMID- 28493057
TI - Absorptance determinations on multicellular tissues.
AB - The analysis of the variation of the capacity and efficiency of photosynthetic
tissues to collect solar energy is fundamental to understand the differences
among species in their ability to transform this energy into organic molecules.
This analysis may also help to understand natural changes in species distribution
and/or abundance, and differences in species ability to colonize contrasting
light environments or respond to environmental changes. Unfortunately, the
challenge that optical determinations on highly dispersive samples represent has
strongly limited the progression of this analysis on multicellular tissues,
limiting our knowledge of the role that optical properties of photosynthetic
tissues may play in the optimization of photosynthesis and growth of benthonic
primary producers. The aim of this study is to stimulate the use of optical tools
in marine eco-physiology, offering a succinct description of the more convenient
tools and also solutions to resolve the more common technical difficulties that
arise while performing optical determinations on highly dispersive samples. Our
study focuses on two-dimensional (2D-) parameters: absorptance, transmittance,
and reflectance, and illustrates with correct and incorrect examples, specific
problems and their respective solutions. We also offer a general view of the
broad variation in light absorption shown by photosynthetic structures of marine
primary producers, and its low association with pigment content. The ecological
and evolutionary functional implications of this variability deserve to be
investigated across different taxa, populations, and marine environments.
PMID- 28493058
TI - C-terminal cleavage of the LH1 alpha-polypeptide in the Sr2+-cultured
Thermochromatium tepidum.
AB - The light-harvesting 1 reaction center (LH1-RC) complex in the thermophilic
purple sulfur bacterium Thermochromatium (Tch.) tepidum binds Ca ions as
cofactors, and Ca-binding is largely involved in its characteristic Q y
absorption at 915 nm and enhanced thermostability. Ca2+ can be biosynthetically
replaced by Sr2+ in growing cultures of Tch. tepidum. However, the resulting Sr2+
substituted LH1-RC complexes in such cells do not display the absorption maximum
and thermostability of those from Ca2+-grown cells, signaling that inherent
structural differences exist in the LH1 complexes between the Ca2+- and Sr2+
cultured cells. In this study, we examined the effects of the biosynthetic Sr2+
substitution and limited proteolysis on the spectral properties and
thermostability of the Tch. tepidum LH1-RC complex. Preferential truncation of
two consecutive, positively charged Lys residues at the C-terminus of the LH1
alpha-polypeptide was observed for the Sr2+-cultured cells. A proportion of the
truncated LH1 alpha-polypeptide increased during repeated subculturing in the
Sr2+-substituted medium. This result suggests that the truncation is a
biochemical adaptation to reduce the electrostatic interactions and/or steric
repulsion at the C-terminus when Sr2+ substitutes for Ca2+ in the LH1 complex.
Limited proteolysis of the native Ca2+-LH1 complex with lysyl protease revealed
selective truncations at the Lys residues in both C- and N-terminal extensions of
the alpha- and beta-polypeptides. The spectral properties and thermostability of
the partially digested native LH1-RC complexes were similar to those of the
biosynthetically Sr2+-substituted LH1-RC complexes in their Ca2+-bound forms.
Based on these findings, we propose that the C-terminal domain of the LH1 alpha
polypeptide plays important roles in retaining proper structure and function of
the LH1-RC complex in Tch. tepidum.
PMID- 28493059
TI - Characterization of OATP1B3 and OATP2B1 transporter expression in the islet of
the adult human pancreas.
AB - Organic anion-transporting polypeptides (OATPs) are membrane proteins that
mediate cellular uptake of structurally diverse endogenous and exogenous
compounds, including bile salts, thyroid and sex hormones, pharmacological
agents, and toxins. Roles of OATPs in human liver are well established. Our
recent report suggested the presence of the hepatic transporter OATP1B3 in human
beta cells. The aim of this study was to better characterize cellular
localization and interindividual variation in OATP1B3 expression in human adult
islets as a function of age, sex, and pancreatic disease, and to assess the
expression of other OATPs. High transcript levels of OATP1B3, OATP2B1, OATP1A2,
but not OATP1B1 were observed in isolated human adult islets. While OATP1B3
protein expression was variable, the carrier co-localized more frequently with
glucagon-positive alpha cells than insulin-positive beta cells in islets of
normal pancreatic tissues from ten subjects using dual immunostaining. Moreover,
OATP1B3 co-staining with endocrine cells was two- to three-fold higher in older
(>=60 years) than younger (<60 years) subjects. In comparison, in a subset of
three individuals, OATP2B1 was primarily found in beta cells, suggesting a
distinct expression pattern for OATP1B3 and OATP2B1 in islets. Abundant OATP1B3
staining was also observed in islet as well as ductal cells of diseased tissues
of patients with pancreatitis or pancreatic adenocarcinoma. Considering the
abundance of key OATP carriers in beta and alpha cells, potential implications of
OATP transport in islet cell function may be suggested. Future studies are needed
to gain insights into their specific endocrine roles as well as pharmacological
relevance.
PMID- 28493060
TI - Synthetic Turf Fields, Crumb Rubber, and Alleged Cancer Risk.
AB - Most synthetic turf fields have crumb rubber interspersed among the simulated
grass fibers to reduce athletic injuries by allowing users to turn and slide more
readily as they play sports or exercise on the fields. Recently, the crumbs have
been implicated in causing cancer in adolescents and young adults who use the
fields, particularly lymphoma and primarily in soccer goalkeepers. This concern
has led to the initiation of large-scale studies by local and federal governments
that are expected to take years to complete. Meanwhile, should the existing
synthetic turf fields with crumb rubber be avoided? What should parents, players,
coaches, school administrators, and playground developers do? What should sports
medicine specialists and other health professionals recommend? Use grass fields
when weather and field conditions permit? Exercise indoors? Three basic premises
regarding the nature of the reported cancers, the latency of exposure to
environmental causes of cancer to the development of clinically detectable
cancer, and the rarity of environmental causation of cancer in children,
adolescents, and young adults suggest otherwise.
PMID- 28493061
TI - Chronotype, Physical Activity, and Sport Performance: A Systematic Review.
AB - BACKGROUND: Many variables related to sport have been shown to have circadian
rhythms. Chronotype is the expression of circadian rhythmicity in an individual,
and three categories of chronotype are defined: morning types (M-types), evening
types (E-types), and neither types (N-types). M-types show earlier peaks of
several psychophysiological variables during the day than E-types. The effect of
chronotype on athletic performance has not been extensively investigated.
OBJECTIVE: The objective of the present review was to study the effect of
chronotype on athletic performance and the psychophysiological responses to
physical activity. METHODS: The present review adheres to the PRISMA (Preferred
Reporting Items for Systematic Reviews and Meta-Analyses) reporting guidelines.
We searched PubMed, Scopus, and Web of Science for scientific papers using the
keywords "chronotype", "circadian typology", "morningness", and "eveningness" in
combination with each of the words "sport", "performance", and "athletic."
Relevant reference lists were inspected. We limited the search results to peer
reviewed papers published in English from 1985 to 2015. RESULTS: Ten papers met
our inclusion criteria. Rating of perceived exertion and fatigue scores in
relation to athletic performances are influenced by chronotype: M-types perceived
less effort when performing a submaximal physical task in the morning than did N-
and E-types. In addition, M-types generally showed better athletic performances,
as measured by race times, in the morning than did N- and E-types. Other results
concerning chronotype effect on physiological responses to physical activity were
not always consistent: heterogeneous samples and different kinds of physical
activity could partially explain these discrepancies. CONCLUSIONS: Sports
trainers and coaches should take into account the influence of both the time of
day and chronotype effect when scheduling training sessions into specific time
periods.
PMID- 28493062
TI - Comment on: "Are Prepubertal Children Metabolically Comparable to Well-Trained
Adult Endurance Athletes?"
PMID- 28493063
TI - Authors' Reply to Dotan and Falk: "Are Prepubertal Children Metabolically
Comparable to Well-Trained Adult Endurance Athletes?"
PMID- 28493064
TI - Evidence-Based Prerequisites and Precursors of Athletic Talent: A Review.
AB - Extensive findings related to nature and nurture in determining athletic talent
(AT) have been reviewed. Available data demonstrate the important contribution of
hereditary factors as well as the crucial importance of environmental
prerequisites for identifying and developing AT. Recent publications provide
examples of contemporary approaches intended to solve the problem of how to
discover and nurture AT. A number of cross-sectional and longitudinal studies
highlighted possibilities of revealing a predisposition to certain sports among
youthful prospects, but were unable to predict attainment of world-class status.
Data pertaining to Olympic champions indicate that their superiority compared
with other elite athletes is determined by high intrinsic motivation,
determination, dedication, persistence, and creativity. These salient
manifestations of personality could be successfully recognized even in the
initial stages of their preparation, where exceptionally gifted individuals
manifested high learnability and a high rate of athletic improvement. Moreover,
future champions were characterized by an exceptional attitude to training and a
willingness to perform more voluminous and high-quality training routines.
Exceptionally talented athletes in endurance, power, and combat sports attained
world-class status after 4-7 years of specialized preparation, accumulating 3000
7000 h of purposeful training. This stands in contradiction to Ericsson's theory
of deliberate practice and the 10-year rule. In contrast, Olympic artistic
gymnastics champions attained world-class status following an average of 9.7
years of specialized preparation, accumulating an average of 8918 h of
specialized training. Apparently, the theory of 10,000 h of deliberate practice
and the 10-year rule are selectively applicable to highly coordinative esthetic
sports but not to general preparation trends in endurance, power, and combat
sports.
PMID- 28493065
TI - Healthcare Utilization by Older Age Groups in Northern States of Peninsular
Malaysia: The Role of Predisposing, Enabling and Need Factors.
AB - Determining factors that affect healthcare utilization by the elderly is vital
for the health system to be more responsive in providing care to this vulnerable
group. The main objective of this paper is to identify the effect of the
predisposing, enabling, and need factors on doctor visits and in-patient care for
the elderly residing in the northern region of Malaysia. A multistage cluster
sampling was used in selecting the sample for the study. A total of 1414
respondents aged 60 and over were interviewed face-to-face using a structured
questionnaire. A probit model was used in estimating the utilization equations.
At a significance level of 0.05, except for age, all predisposing and enabling
factors were not statistically significant in affecting the doctor visits. On the
other hand, being a male, smoker, medical insurance holder or had not actively
involved in social interaction within the reference period increases the
likelihood of being in-patient. Health-related variables remain the most
significant factors that determine healthcare utilization, including both doctor
visits and in-patient stays, in the area of study, which suggests that government
policies to improve population health may influence the level of healthcare use
in the future.
PMID- 28493066
TI - Cognition and balance control: does processing of explicit contextual cues of
impending perturbations modulate automatic postural responses?
AB - Processing of predictive contextual cues of an impending perturbation is thought
to induce adaptive postural responses. Cueing in previous research has been
provided through repeated perturbations with a constant foreperiod. This
experimental strategy confounds explicit predictive cueing with adaptation and
non-specific properties of temporal cueing. Two experiments were performed to
assess those factors separately. To perturb upright balance, the base of support
was suddenly displaced backwards in three amplitudes: 5, 10 and 15 cm. In
Experiment 1, we tested the effect of cueing the amplitude of the impending
postural perturbation by means of visual signals, and the effect of adaptation to
repeated exposures by comparing block versus random sequences of perturbation. In
Experiment 2, we evaluated separately the effects of cueing the characteristics
of an impending balance perturbation and cueing the timing of perturbation onset.
Results from Experiment 1 showed that the block sequence of perturbations led to
increased stability of automatic postural responses, and modulation of magnitude
and onset latency of muscular responses. Results from Experiment 2 showed that
only the condition cueing timing of platform translation onset led to increased
balance stability and modulation of onset latency of muscular responses.
Conversely, cueing platform displacement amplitude failed to induce any effects
on automatic postural responses in both experiments. Our findings support the
interpretation of improved postural responses via optimized sensorimotor
processes, at the same time that cast doubt on the notion that cognitive
processing of explicit contextual cues advancing the magnitude of an impending
perturbation can preset adaptive postural responses.
PMID- 28493068
TI - Cathepsin S increases tau oligomer formation through limited cleavage, but only
IL-6, not cathespin S serum levels correlate with disease severity in the
neurodegenerative tauopathy progressive supranuclear palsy.
AB - Limited cleavage promotes the aggregation propensity of protein tau in
neurodegenerative tauopathies. Cathepsin S (CatS) is overexpressed in brains of
patients suffering from tauopathies such as Alzheimer's disease (AD).
Furthermore, CatS serum levels correlate with survival in the elderly. The
current study investigates whether limited cleavage by CatS promotes tau
aggregation, and whether CatS serum levels may correlate with disease severity in
tauopathies. Oligomer formation of fluorescently labeled protein tau was
monitored by single particle fluorescence spectroscopy after coincubation with
CatS. Tau cleavage patterns were investigated by SDS-PAGE. For serum analyses,
samples were collected from 42 patients with probable progressive supranuclear
palsy (PSP) according to NINDS-PSP criteria. Disease severity was assessed by PSP
rating scale (PSP-RS), PSP staging system (PSP-S) and Schwab and England
Activities of Daily Living (SEADL). CatS, cystatin C (CysC) and interleukin 6 (IL
6) serum levels were determined by ELISA, ECLIA and turbidimetry, respectively.
SDS-PAGE demonstrated a distinct cleavage pattern of protein tau after
coincubation with CatS. Furthermore, tau oligomer formation was increased 2.4
fold (p < 0.05) after limited cleavage. Serum CatS and CysC levels did not
correlate with disease severity in PSP. Of note, IL-6 correlated with PSP-S (r =
0.41; 95% CI 0.11-0.65; p = 0.008), SEADL (r = -0.37; 95% CI -0.61 to -0.06; p =
0.017) and the history and gait/midline subdomains of the PSP-RS. While CatS
facilitates tau aggregation in vitro, serum levels of CatS appear not to
correlate with disease severity. The observed correlation of IL-6 with disease
severity warrants further investigation of inflammatory markers in PSP.
PMID- 28493067
TI - Visuotactile interaction even in far sagittal space in older adults with
decreased gait and balance functions.
AB - Spatial proximity of signals from different sensory modalities is known to be a
crucial factor in facilitating efficient multisensory processing in young adults.
However, recent studies have demonstrated that older adults exhibit strong
visuotactile interactions even when the visual stimuli were presented in a
spatially disparate position from a tactile stimulus. This suggests that
visuotactile peripersonal space differs between older and younger adults. In the
present study, we investigated to what extent peripersonal space expands in the
sagittal direction and whether this expansion was linked to the decline in
sensorimotor functions in older adults. Vibrotactile stimuli were delivered
either to the left or right index finger, while visual stimuli were presented at
a distance of 5 cm (near), 37.5 cm (middle), or 70 cm (far) from each finger. The
participants had to respond rapidly to a randomized sequence of unimodal (visual
or tactile) and simultaneous visuotactile targets (i.e., a redundant target
paradigm). Sensorimotor functions were independently assessed by the Timed Up and
Go (TUG) and postural stability tests. Results showed that reaction times to the
visuotactile bimodal stimuli were significantly faster than those to the unimodal
stimuli, irrespective of age group [younger adults: 22.0 +/- 0.6 years, older
adults: 75.0 +/- 3.3 years (mean +/- SD)] and target distance. Of importance, a
race model analysis revealed that the co-activation model (i.e., visuotactile
multisensory integrative process) is supported in the far condition especially
for older adults with relatively poor performance on the TUG or postural
stability tests. These results suggest that aging can change visuotactile
peripersonal space and that it may be closely linked to declines in sensorimotor
functions related to gait and balance in older adults.
PMID- 28493070
TI - Quality of routine diagnostic abdominal images generated from a novel detector
based spectral CT scanner: a technical report on a phantom and clinical study.
AB - PURPOSE: To evaluate the image quality of routine diagnostic images generated
from a novel detector-based spectral detector CT (SDCT) and compare it with CT
images obtained from a conventional scanner with an energy-integrating detector
(Brilliance iCT), Routine diagnostic (conventional/polyenergetic) images are non
material-specific images that resemble single-energy images obtained at the same
radiation, METHODS: ACR guideline-based phantom evaluations were performed on
both SDCT and iCT for CT adult body protocol. Retrospective analysis was
performed on 50 abdominal CT scans from each scanner. Identical ROIs were placed
at multiple locations in the abdomen and attenuation, noise, SNR, and CNR were
measured. Subjective image quality analysis on a 5-point Likert scale was
performed by 2 readers for enhancement, noise, and image quality. RESULTS: On
phantom studies, SDCT images met the ACR requirements for CT number and
deviation, CNR and effective radiation dose. In patients, the qualitative scores
were significantly higher for the SDCT than the iCT, including enhancement (4.79
+/- 0.38 vs. 4.60 +/- 0.51, p = 0.005), noise (4.63 +/- 0.42 vs. 4.29 +/- 0.50, p
= 0.000), and quality (4.85 +/- 0.32, vs. 4.57 +/- 0.50, p = 0.000). The SNR was
higher in SDCT than iCT for liver (7.4 +/- 4.2 vs. 7.2 +/- 5.3, p = 0.662),
spleen (8.6 +/- 4.1 vs. 7.4 +/- 3.5, p = 0.152), kidney (11.1 +/- 6.3 vs. 8.7 +/-
5.0, p = 0.033), pancreas (6.90 +/- 3.45 vs 6.11 +/- 2.64, p = 0.303), aorta
(14.2 +/- 6.2 vs. 11.0 +/- 4.9, p = 0.007), but was slightly lower in lumbar
vertebra (7.7 +/- 4.2 vs. 7.8 +/- 4.5, p = 0.937). The CNR of the SDCT was also
higher than iCT for all abdominal organs. CONCLUSION: Image quality of routine
diagnostic images from the SDCT is comparable to images of a conventional CT
scanner with energy-integrating detectors, making it suitable for diagnostic
purposes.
PMID- 28493069
TI - Comparison of molecular marker expression in early zebrafish brain development
following chronic ethanol or morpholino treatment.
AB - This study was undertaken to ascertain whether defined markers of early zebrafish
brain development are affected by chronic ethanol exposure or morpholino
knockdown of agrin, sonic hedgehog, retinoic acid, and fibroblast growth factors,
four signaling molecules that are suggested to be ethanol sensitive. Zebrafish
embryos were exposed to 2% ethanol from 6 to 24 hpf or injected with agrin, shha,
aldh1a3, or fgf8a morpholinos. In situ hybridization was employed to analyze
otx2, pax6a, epha4a, krx20, pax2a, fgf8a, wnt1, and eng2b expression during early
brain development. Our results showed that pax6a mRNA expression was decreased in
eye, forebrain, and hindbrain of both chronic ethanol exposed and select MO
treatments. Epha4a expression in rhombomere R1 boundary was decreased in chronic
ethanol exposure and aldh1a3 morphants, lost in fgf8a morphants, but largely
unaffected in agrin and shha morphants. Ectopic pax6a and epha4a expression in
midbrain was only found in fgf8a morphants. These results suggest that while
chronic ethanol induces obvious morphological change in brain architecture, many
molecular markers of these brain structures are relatively unaffected by ethanol
exposure.
PMID- 28493071
TI - Nontraumatic large bowel perforation: spectrum of etiologies and CT findings.
AB - Large bowel perforation is an abdominal emergency that results from a wide range
of etiologies. Computed tomography is the most reliable modality in detecting the
site of large bowel perforation. The diagnosis is made by identifying direct CT
findings such as extraluminal gas or contrast and discontinuity along the bowel
wall. Indirect CT findings can help support the diagnosis, and include bowel wall
thickening, pericolic fat stranding, abnormal bowel wall enhancement, abscess,
and a feculent collection adjacent to the bowel. Common etiologies that cause
large bowel perforation are colon cancer, foreign body aspiration, stercoral
colitis, diverticulitis, ischemia, inflammatory and infectious colitides, and
various iatrogenic causes. Recognizing a large bowel perforation on CT can be
difficult at times, and there are various entities that may be misinterpreted as
a colonic perforation. The purpose of this article is to outline the MDCT
technique used for evaluation of suspected colorectal perforation, discuss
relevant imaging findings, review common etiologies, and point out potential
pitfalls in making the diagnosis of large bowel perforation.
PMID- 28493072
TI - Arterial injury during transcatheter arterial chemoembolization for
hepatocellular carcinoma: predictors of risk and outcome.
AB - PURPOSE: To investigate clinical features and results of follow-up in patients
with arterial injury during transcatheter arterial chemoembolization (TACE) for
hepatocellular carcinoma. METHODS: From 2005 to 2015, 2219 TACE procedures were
performed in 906 patients in our hospital. Iatrogenic arterial injury occurred
during 38 TACE procedures (sessions) in 35 patients (24 men, 11 women; mean age
71.8 years). The incidence of arterial injury was 1.7%. We evaluated the
characteristics of arterial injury, and evaluated the risk factors for incomplete
recanalization of the injured artery at follow-up angiography conducted after 1
11 months (mean 102.5 days). RESULTS: Iatrogenic arterial injury was caused by
the microcatheter in 34 of 38 cases (86.8%). There were 15 cases (39.5%) in which
the replaced hepatic artery or the extrahepatic artery was the parasitic supply.
Extravasation occurred in five cases. In 36 of 38 cases, follow-up angiography
was performed. We divided 36 cases into two groups: complete reopening (n = 24)
and non-complete reopening (n = 12). The two groups were compared regarding the
factors associated with incomplete recanalization of the injured artery at follow
up. Injury length >3 cm (p = 0.0002) and proximal arterial injury (proximal to
the segmental artery; p = 0.03) were significant risk factors for non-complete
reopening of the injured artery. CONCLUSION: Iatrogenic arterial injury
frequently occurred in the extrahepatic artery or replaced hepatic artery.
Recanalization rate of arterial injury was high; however, injury length >3 cm and
proximal arterial injury were risk factors for non-complete reopening of the
injured artery.
PMID- 28493073
TI - Gastroduodenal and pancreatic surgeries: indications, surgical techniques, and
imaging features.
AB - This review article focuses on gastroduodenal and pancreatic surgeries with the
goal of identifying radiologic findings that translate to important surgical
considerations. The topics covered include partial gastrectomy with
reconstruction techniques, total gastrectomy, pancreaticoduodenectomy, and
pancreaticojejunostomy. Indications, contraindications, surgical techniques, and
postoperative imaging are described within each of these topics. Knowledge of
these surgical techniques is extremely helpful for the interpreting radiologists
to identify expected postoperative anatomy and related complications that would
remain clinically relevant to our surgical colleagues and direct timely patient
management.
PMID- 28493074
TI - Corrective osteotomies of the lower limb show a low intra- and perioperative
complication rate-an analysis of 1003 patients.
AB - PURPOSE: The purpose of corrective osteotomies in posttraumatic and congenital
deformities is anatomic limb reconstruction and joint preservation. The aim of
the present study was to analyse intra- and perioperative complications of
osteotomies in the lower limb. METHODS: One thousand and three unselected and
prospectively registered osteotomies of the long bones of the lower limb,
performed between 1995 and 2013, were analysed. In 435 women and 568 men (mean
age 39.8 years), 478 correction osteotomies were performed femoral and 525
tibial; 696 osteotomies were performed using the oscillating saw, 42 using the
Gigli saw and 265 using drill hole/chisel osteoclasis. A total of 869 deformities
were corrected in the acute setting and 134 were corrected continuously via
callotaxis. RESULTS: Seventeen (1.7%) major complications requiring revision
surgeries were detected: 4 arterial injuries, 2 haematomas, 4 compartment
syndromes and 7 deep wound infections. All vascular injuries 4 (0.7%) occurred in
osteotomies around the knee (n = 563). Nineteen (1.9%) minor complications could
be managed by conservative means: 3 (0.3%) deep vein thromboses and 16 (1.6%)
superficial wound infections. No osteomyelitis, pulmonary embolism or death
occurred. Gigli saw osteotomy was stained by a higher infection rate. In male
patients (p = 0.02), posttraumatic deformities (ns) and continuous procedures (p
= 0.025) have a higher risk of superficial infections. No further risks were
detected for age, weight, smoking habit and anatomic level of surgery.
CONCLUSION: Osteotomies around the knee show a very low complication rate. Less
aggressive oscillating saws, saw blades and drills are recommended. Vascular
injuries, compartment syndromes and deep infections are limb-threatening
emergencies demanding fast and determined interventions. LEVEL OF EVIDENCE:
Prospective cohort study, Level III.
PMID- 28493075
TI - MicroRNA-1 acts as a tumor suppressor microRNA by inhibiting angiogenesis-related
growth factors in human gastric cancer.
AB - BACKGROUND: We recently reported that miR-1 was one of the most significantly
downregulated microRNAs in gastric cancer (GC) patients from The Cancer Genome
Atlas microRNA sequencing data. Here we aim to elucidate the role of miR-1 in
gastric carcinogenesis. METHODS: We measured miR-1 expression in human GC cell
lines and 90 paired primary GC samples, and analyzed the association of its
status with clinicopathological features. The effect of miR-1 on GC cells was
evaluated by proliferation and migration assay. To identify the target genes of
miR-1, bioinformatic analysis and protein array analysis were performed.
Moreover, the regulation mechanism of miR-1 with regard to these predicted
targets was investigated by quantitative PCR (qPCR), Western blot, ELISA, and
endothelial cell tube formation. The putative binding site of miR-1 on target
genes was assessed by a reporter assay. RESULTS: Expression of miR-1 was
obviously decreased in GC cell lines and primary tissues. Patients with low miR-1
expression had significantly shorter overall survival compared with those with
high miR-1 expression (P = 0.0027). Overexpression of miR-1 in GC cells inhibited
proliferation, migration, and tube formation of endothelial cells by suppressing
expression of vascular endothelial growth factor A (VEGF-A) and endothelin 1
(EDN1). Conversely, inhibition of miR-1 with use of antago-miR-1 caused an
increase in expression of VEGF-A and EDN1 in nonmalignant GC cells or low
malignancy GC cells. CONCLUSIONS: MiR-1 acts as a tumor suppressor by inhibiting
angiogenesis-related growth factors in human gastric cancer. Downregulated miR-1
not only promotes cellular proliferation and migration of GC cells, but may
activates proangiogenesis signaling and stimulates the proliferation and
migration of endothelial cells, indicating the possibility of new strategies for
GC therapy.
PMID- 28493076
TI - Extracellular vesicles regulate the human osteoclastogenesis: divergent roles in
discrete inflammatory arthropathies.
AB - OBJECTIVE: Extracellular vesicles (EVs) are subcellular signalosomes. Although
characteristic EV production is associated with numerous physiological and
pathological conditions, the effect of blood-derived EVs on bone homeostasis is
unknown. Herein we evaluated the role of circulating EVs on human
osteoclastogenesis. METHODS: Blood samples from healthy volunteers, rheumatoid
arthritis (RA) and psoriatic arthritis (PsA) patients were collected. Size-based
EV sub-fractions were isolated by gravity-driven filtration and differential
centrifugation. To investigate the properties of EV samples, resistive pulse
sensing technique, transmission electron microscopy, flow cytometry and western
blot were performed. CD14+ monocytes were separated from PBMCs, and stimulated
with recombinant human M-CSF, RANKL and blood-derived EV sub-fractions. After 7
days, the cells were fixed and stained for tartrate-resistant acid phosphatase
and counted. RESULTS: EVs isolated by size-based sub-fractions were characterized
as either microvesicles or exosomes (EXO). Healthy (n = 11) and RA-derived (n =
12) EXOs profoundly inhibited osteoclast differentiation (70%, p < 0.01; 65%, p <
0.01, respectively). In contrast, PsA-derived (n = 10) EXOs had a stimulatory
effect (75%, p < 0.05). In cross-treatment experiments where EXOs and CD14+ cells
were interchanged between the three groups, only healthy (n = 5) and RA (n = 5)
derived EXOs inhibited (p < 0.01, respectively) the generation of osteoclasts in
all groups, whereas PsA (n = 7)-derived EXOs were unable to mediate this effect.
CONCLUSIONS: Our data suggest that blood-derived EXOs are novel regulators of the
human osteoclastogenesis and may offer discrete effector function in distinct
inflammatory arthropathies.
PMID- 28493077
TI - Lung Protective Effects of Low-Volume Resuscitation and Pharmacologic Treatment
of Swine Subjected to Polytrauma and Hemorrhagic Shock.
AB - Hemorrhage is a common cause of death in the battlefield. Valproic acid (VPA) has
been associated with improved outcomes in multiple models of trauma, when
combined with isotonic fluid resuscitation. However, isotonic fluid administered
in this setting is logistically impractical and may be associated with
complications. In this study, we sought to evaluate the feasibility and
immunologic impact of combining VPA treatment with low-volume hypertonic saline
(HTS). In vivo: female Yorkshire swine were subjected to hemorrhage (40% total
blood volume) and polytrauma (rib fracture and delayed liver injury). Animals
were kept in shock for 30 minutes and resuscitated with (1) normal saline (NS, 3*
hemorrhaged volume), (2) HTS (7.5% saline, 4 mL/kg), or (3) HTS + VPA (4 mg/kg;
150 mg/kg; n = 3/cohort). After 18 hours of observation, animals were euthanized
and the lungs evaluated for acute injury and expression of myeloperoxidase (MPO)
and caveolin-1 (Cav-1). In vitro: human umbilical vein endothelial cells (HUVECs)
were exposed to anoxic conditions (5% CO2, 95% N2) for 16 hours in (1)
normosmotic, (2) hyperosmotic (400 mOsm), or (3) hyperosmotic + VPA (4 mM) media.
Immunohistochemistry and Western blots were performed to determine Cav-1
expression. Lungs from VPA-treated animals demonstrated decreased acute injury,
MPO expression, and endothelial expression of Cav-1 when compared to lungs from
animals resuscitated with NS or HTS alone. Similarly, HUVECs cultured in
hyperosmotic media containing VPA demonstrated decreased expression of Cav-1.
This study demonstrates that combined treatment with VPA and HTS is a viable
strategy in hemorrhagic shock and polytrauma. Attenuation of lung injury
following VPA treatment may be related to modulation of the inflammatory
response.
PMID- 28493078
TI - The 5-HT3 Receptor Antagonist Ondansetron Attenuates Pancreatic Injury in
Cerulein-Induced Acute Pancreatitis Model.
AB - The 5-hydroxytryptamine-3 receptor (5-HT3R) antagonist ondansetron has been
clinically approved as an anti-emetic agent. Recent findings indicate that
ondansetron has anti-inflammatory properties. The aim of the present study was to
assess the therapeutic action of ondansetron in cerulein-induced acute
pancreatitis model. Male-BALB/c mice were used in the present study. Acute
pancreatitis was induced by an hourly injection of cerulein. Ondansetron was
administered subcutaneously at a dose of 3 mg/kg. The messenger RNA (mRNA)
expression of 5-HT3 R in pancreatic tissue was assessed with RT-PCR. Plasma
amylase, lipase, and interleukin (IL)-6 levels were evaluated. Pancreatic injury
was histopathologically graded, and myeloperoxidase (MPO)-positive cells were
counted. 5-HT3R mRNA was expressed in the pancreas. In acute pancreatitis model
mice, amylase, lipase, and IL-6 levels were significantly increased in the blood.
With ondansetron treatment, these levels were significantly decreased.
Histopathological evaluation revealed that ondansetron attenuated the
inflammatory damage in acute pancreatitis. The number of infiltrated neutrophils
stained by MPO was decreased by ondansetron treatment. In summary, the 5-HT3R
antagonist ondansetron attenuated pancreatic injury through its anti-inflammatory
action. These findings suggest that ondansetron may potentially be of use for
therapy of acute pancreatitis.
PMID- 28493079
TI - TLR2 Regulates Allergic Airway Inflammation and Autophagy Through PI3K/Akt
Signaling Pathway.
AB - Toll-like receptors (TLRs) are innate pattern recognition receptors that play a
critical role in allergic inflammation, yet their contribution to autophagy in
asthma remains poorly defined. Here, we investigate the role of Toll-like
receptor 2 (TLR2) in phosphoinositide 3-kinases/protein kinase B (PI3K/Akt)
pathway-mediated autophagy in ovalbumin-induced airway inflammation in mice. Wild
type (WT) and TLR2-knockout (TLR2-/-) C57BL/6 mice were ovalbumin-sensitized and
ovalbumin-challenged. In ovalbumin-challenged WT mice, enhanced expression of
TLR2 in lung tissue, remarkable inflammatory cell infiltrates, goblet cell
hyperplasia, and increased mucus production were observed. The number of
inflammatory cells and interleukin-13 (IL-13) levels increased, while interferon
gamma (IFN-gamma) levels decreased in bronchoalveolar lavage fluid. Expression of
PI3K, phospho-Akt, Beclin-1 and LC3-II was enhanced significantly. These changes
were mitigated dose-dependently in 3-methyl adenine-treated mice. In contrast,
similar but weaker changes were found in ovalbumin-challenged TLR2-/- mice, and
the changes were not significantly attenuated by 3-methyl adenine treatment.
These results indicate that TLR2 confers a pivotal role in allergic airway
inflammation via regulating the PI3K/Akt signaling pathway-related autophagy in
mice.
PMID- 28493080
TI - Therapeutic Action of Honokiol on Postoperative Ileus via Downregulation of iNOS
Gene Expression.
AB - Postoperative ileus is a common complication after intra-abdominal surgery.
Nitric oxide produced by macrophages in the inflamed gastrointestinal tract plays
a crucial role in the pathogeny of postoperative ileus. Honokiol, extracted from
the bark of Magnolia spp., is a natural compound with a biphenolic structure. In
the present study, we examined the effect of honokiol on postoperative ileus and
discussed its site of action. Postoperative ileus model mice were generated by
surgical intestinal manipulation. Mice were administered honokiol (10 mg kg-1,
per os) 1 h before and after intestinal manipulation. Gastrointestinal transit,
leukocyte infiltration, and messenger RNA (mRNA) expression of inflammatory
mediators were measured in postoperative ileus model mice with or without
honokiol. We also investigated the inflammatory effect of honokiol in
lipopolysaccharide-stimulated peritoneal macrophages. Gastrointestinal transit
was delayed in postoperative ileus model mice and honokiol recovered the impaired
transit. Honokiol significantly inhibited leukocyte infiltration and upregulation
of proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, and
interleukin-6) and inducible nitric oxide synthase in the ileal muscle layer of
postoperative ileus model mice. In peritoneal macrophages activated by
lipopolysaccharide, honokiol significantly inhibited the upregulated mRNA
expression of proinflammatory cytokines and inducible nitric oxide synthase.
Honokiol significantly recovered gastrointestinal dysmotility and inhibited
intestinal inflammation in postoperative ileus. Moreover, honokiol was suggested
to have effects on macrophages, namely, inhibiting mRNA expression of
proinflammatory cytokines and inducible nitric oxide synthase. Taken together,
honokiol represents a potential novel therapeutic agent for postoperative ileus.
PMID- 28493081
TI - Regulation of iNOS-Derived ROS Generation by HSP90 and Cav-1 in Porcine
Reproductive and Respiratory Syndrome Virus-Infected Swine Lung Injury.
AB - In the lungs, endothelial nitric oxide synthase (eNOS) is usually expressed in
endothelial cells and inducible nitric oxide synthase (iNOS) is mainly expressed
in alveolar macrophages and epithelial cells. Both eNOS and iNOS are involved in
lung inflammation. While they play several roles in lung inflammation formation
and resolution, their expression and activity are also regulated by inflammatory
factors. Their expression relationship in virus infection-induced lung injury is
not well addressed. In this report, we analyzed expression of both eNOS and iNOS,
the production of nitric oxide (NO) and reactive oxygen species (ROS), and
expression of their associated regulatory proteins, heat shock protein 90 (HSP90)
and caveolin-1 (Cav-1), in a swine lung injury model induced by porcine
reproductive and respiratory syndrome virus (PRRSV) infection. The combination of
upregulation of iNOS and downregulation of eNOS was observed in both natural and
experimental PRRSV-infected lungs, while the combination is much enhanced in
natural infected lungs. While NO production is much reduced in both infections,
ROS was enhanced only in natural infected lungs. Moreover, HSP90 is increased in
both natural and experimental infection and less Cav-1 expressed was observed
only in the natural PRRSV-infected lungs. Therefore, the increased ROS generation
is likely due to the increased iNOS and its unbalanced regulation by HSP90 and
Cav-1, and it also likely causes higher endothelial dysfunction in clinical PRRSV
infected lungs.
PMID- 28493082
TI - Electro-Acupuncture at Zusanli Acupoint (ST36) Suppresses Inflammation in
Allergic Contact Dermatitis Via Triggering Local IL-10 Production and Inhibiting
p38 MAPK Activation.
AB - Acupuncture has shown beneficial effect in the treatment of multiple dermatologic
conditions including dermatitis, pruritus, urticaria, and hyperhidrosis; however,
the detailed mechanisms are still kept unclear. This study aimed to investigate
if electro-acupuncture (EA) treatment prevents 2,4-dinitrofluorobenzene (DNFB)
induced allergic contact dermatitis (ACD) in rats and explore its underlying
mechanisms. ACD was induced by sensitizing and challenging with DNFB topically.
Rats were treated daily following bilateral subcutaneous stimulation of EA at
Zusanli acupoint (ST36) for 1 week. Ear swelling and serum IgE levels were
measured. The ear biopsies were obtained for histology. Inflammatory cytokines on
the dermatological ear and local acupoint tissue were assayed. Spleen lymphocytes
and the homogenized supernatant of local acupuncture area were used to co-culture
for flow cytology and immune analysis, respectively. EA treatment at ST36 notably
inhibited ear swelling and inflammatory cell infiltration on DNFB-induced ACD. EA
also decreased serum IgE concentrations and alleviated the production of
inflammatory cytokines in dermatological ear. Additionally, EA treatment
attenuated the percentage of CD4+IFN-gamma+ and CD4+IL-4+ T cells associated with
ACD. Interestingly, secretion of interleukin (IL)-10 in the local acupoint tissue
following EA stimulation was increased and showed suppressive function when co
cultured with the spleen lymphocytes from DNFB group. Lastly, EA treatment
demonstrably suppressed p38 MAPK activation in DNFB-treated rats. Our findings
suggest that EA treatment at ST36 may ameliorate inflammation associated with
DNFB-induced ACD via triggering local IL-10 production and inhibiting p38 MAPK
activation, which provide an alternative and promising therapy for ACD.
PMID- 28493083
TI - Protective Effects of Acupuncture in Cardiopulmonary Bypass-Induced Lung Injury
in Rats.
AB - Acute lung injury caused by cardiopulmonary bypass (CPB) increases the mortality
after cardiac surgery. Our previous clinical study suggested that
electroacupuncture (EAc) has a protective effect during CPB, but the mechanism
was unclear. So, we design this study to investigate the effects of EAc on CPB
induced lung injury and the underlying mechanism. Male Sprague Dawley rats were
randomly divided into control, CPB, and CPB + EAc groups. A lung injury model was
created by CPB surgery to serve as the CPB group, and EAc (2/100 Hz) was used
before CPB in the CPB + EAc group. Lung tissue was collected at 0.5, 1, and 2 h
after CPB. Pulmonary malondialdehyde (MDA) concentrations as well as superoxide
dismutase (SOD), myeloperoxidase (MPO), and caspase-3 activity were determined. c
Jun N-terminal kinase (JNK), ERK, p38 and cleaved caspase 3 in the lung were
analyzed by western blotting. A549 cells were treated by rat serum from the CPB
and CPB + EAc groups, and cleaved caspase-3 activity was detected by fluorescent
immunohistochemistry. CPB significantly increased the MPO activity, MDA content,
apoptosis, caspase-3 activity, and phosphorylated p38 but decreased SOD activity
compared with the control group. EAc significantly increased SOD activity at 0.5
and 2 h (p < 0.01 vs CPB) and reduced CPB-induced histological changes, MPO
activity at 1 and 2 h (p < 0.05 vs CPB), MDA content at 2 h (p < 0.05 vs CPB),
caspase-3 activity at 1 h (p < 0.05 vs CPB), and phosphorylated p38 and JNK at
0.5 h after CPB. The serum from the CPB group increased more positive staining
cells of cleaved caspase-3 than that from the CPB + EAc group. EAc reversed the
CPB-induced lung inflammation, oxidative damage, and apoptosis; the mechanism may
involve decreased phosphorylation of p38 along with caspase-3 activity and
activation.
PMID- 28493084
TI - Combined intracoronary 2D-3D optical coherence tomography and intravascular
ultrasound imaging in left main severe stent malapposition.
PMID- 28493085
TI - Pericardial Effusion and Cardiac Tamponade in the New Millennium.
AB - PURPOSE OF REVIEW: The purpose of this paper is to review current approaches to
the diagnosis and treatment of pericardial effusions and cardiac tamponade.
RECENT FINDINGS: Recent recommendations from the American Society of
Echocardiography and the European Society of Cardiology have refined our
approaches to the patient with pericardial effusion and cardiac tamponade, but
significant knowledge gaps remain. New diagnostic and triage strategies have been
proposed, and recent data have advanced our ability to assess the presence and
size of a pericardial effusion, assess its hemodynamic impact, and establish its
cause. Despite these recent findings, there is a paucity of evidence-based data
to guide the management of pericardial effusion and cardiac tamponade. While the
first-line function of echocardiography in managing these disorders is
unquestioned, there are increasing niche roles for multimodality imaging.
PMID- 28493086
TI - Ranibizumab for choroidal neovascularization secondary to pseudoxanthoma
elasticum: 4-year results from the PIXEL study in France.
AB - PURPOSE: To evaluate the long-term effectiveness and safety of ranibizumab 0.5 mg
in patients with choroidal neovascularization (CNV) secondary to pseudoxanthoma
elasticum (PXE) in a real-world setting. METHODS: A descriptive, observational,
multicenter study in a retrospective and prospective cohort was conducted in
France that included patients who had received at least one injection of
ranibizumab 0.5 mg during the period October 2011 to October 2014, for CNV
secondary to PXE. Eligible patients were identified by review of medical records
or during routine consultations. The main objectives were to describe patient
characteristics, assess changes in best-corrected visual acuity [VA, Early
Treatment Diabetic Retinopathy Study (ETDRS) letters] over time, the number and
reasons for ranibizumab treatment and overall safety. RESULTS: Of the 72 enrolled
patients (98 eyes) from 23 centers, 39 (54.2%) were male and mean [+/-standard
deviation (SD)] age was 59.6 (+/-8.3) years. The mean VA was 64.6 letters at the
first ranibizumab injection, which was maintained at the 1-year follow-up (64.7
letters). Thereafter, the mean VA was stable until the 4-year follow-up. At 4
years, the proportion of eyes with VA gain of >=15 letters was 3/19 (15.8%) and
stable VA (change between -15 and +15 letters) was 10/19 (52.6%). Mean (+/-SD)
annual number of ranibizumab injections was 4.1 (+/-4.0), lower in the second
versus first year. The most common reason for ranibizumab treatment was
progression of neovascular activity (42.9%). No deaths or new safety findings
were reported. CONCLUSIONS: In patients with CNV secondary to PXE, ranibizumab
0.5 mg resulted in stable VA over 4 years with a limited number of injections.
Safety findings were consistent with the established safety profile of
ranibizumab.
PMID- 28493087
TI - Ciliary body thickness changes after preoperative anti-inflammatory treatment in
rhegmatogenous retinal detachment complicated by choroidal detachment.
AB - BACKGROUND: The literature is scant on the state of the ciliary body, its role in
the development of rhegmatogenous retinal detachment (RRD) complicated by
choroidal detachment (CD), and on ciliary body changes following the treatment
aimed at resolving concomitant inflammation and choroidal attachment. This study
assesses the anatomical position and thickness of the ciliary body and
investigates the ciliary body changes after anti-inflammatory pre-vitrectomy
treatment in RRD complicated by CD. METHODS: Forty-nine patients (49 eyes) with
RRD complicated by CD underwent standard ophthalmological examination (including
visual acuity assessment, biomicroscopy, ophthalmoscopy, and ocular tonometry)
and ultrasound biomicroscopy of the ciliary body, choroid, and retina both before
and following anti-inflammatory pre-vitrectomy treatment. RESULTS: At baseline,
all subject eyes had ciliary body edema and detachment extending into the
choroid. Ultrasonographic ciliary features included ciliary body edema and
disorganization of the supraciliary layer of the pars plana, which was evident by
the presence of multiple small oblique fibers. In all subject eyes, the treatment
resulted in reattachment of the choroid and the ciliary body as well as a
reduction in ciliary body edema (total mean ciliary thickness reduced from 0.83
(0.09) to 0.65 (0.09) mm, with a difference of 0.18 (0.07) mm, P < 0.001).
CONCLUSIONS: Preoperative anti-inflammatory treatment in RRD complicated by CD
results in restoration of the anatomical position of the ciliary body and a
statistically significant reduction in ciliary body edema.
PMID- 28493088
TI - Establishing a Framework for a Natural Area Taxonomy.
AB - The identification of areas of endemism is essential in building an area
classification, but plays little role in how natural areas are discovered. Rather
area monophyly, derived from cladistics, is essential in the discovery of natural
area classifications or area taxonomy. We propose Area Taxonomy to be a new sub
discipline of historical biogeography, one that can be revised and debated, and
which has its own area nomenclature. Separately to area taxonomy, we outline how
natural areas may be discovered by transcribing the concepts of homology and
monophyly from biological systematics to historical biogeography, in the form of
area homologues, area homologies and area monophyly.
PMID- 28493090
TI - [Impaired recognition of environmental sounds in patients with dementia : I can
hear but I do not understand].
AB - BACKGROUND: Impairment of central auditory processing is a well-known symptom of
neurodegenerative dementia; however, whilst numerous studies have examined verbal
processing impairment, to date few have attempted to describe impairments of non
verbal, environmental sound recognition in patients with dementia. As these
impairments may have direct implications on patient support and care, such
studies are urgently necessary. AIM OF THE STUDY: The aim of the study was to
determine whether the recognition of meaningful environmental sounds is impaired
in patients with mild or early stage neurodegenerative dementia. PATIENTS AND
METHODS: We developed a test of non-verbal sound recognition consisting of 16
sound sequences from the familiar and unfamiliar environments. We included 18
patients with mild cognitive impairment and mild dementia caused by Alzheimer's
disease and frontotemporal dementia, as well as 20 cognitively healthy controls.
RESULTS: Patients and controls were given the test of recognizing 16 meaningful
sounds from the familiar and unfamiliar environments. Patients with dementia
performed significantly worse in comparison to cognitively healthy controls.
Whilst healthy controls correctly recognized on average 12.1 +/- 2.2 out of 16
sounds, cognitively impaired patients recognized 9.2 +/- 2.5. Correlation
analysis showed that the mini mental state examination (MMSE) scores were
positively correlated with the number of correctly recognized sounds (MMSE: r =
0.556, p = 0.017). DISCUSSION: The fact that even in mild stages of Alzheimer's
disease or frontotemporal dementia patients either do not recognize or
misinterpret environmental sounds must be taken into consideration not only in
everyday life but in particular when patients need to leave their familiar living
environment, whether temporarily (e. g. hospitalization) or permanently (e. g.
nursing home admission).
PMID- 28493091
TI - [Violence against the elderly in domestic care settings : Short profile of an
interdisciplinary research project].
AB - Most elderly people wish to remain and be cared for in their own home.
Approximately 1.38 million people in Germany are cared for without professional
support. However, domestic care by relatives can be a risk factor for violence
against the elderly. This research project deals with the issue from a legal and
social sciences perspective. The aim of the project is to develop a regulatory
framework providing aid-oriented prevention and intervention in the family care
of vulnerable elderly people by public agencies and courts. Firstly, empirical
data on the situation in family care will be analyzed; secondly, the existing
legal framework will be examined. In a third step, recommendations for
legislation and administration will be developed in collaboration with
practitioners. Initial findings show that, although various support, advice, and
training services exist, the situation at home is not always safe. There is a
lack of legal regulation on the issue of abuse in the family care setting,
especially compared with German legislation on child protection. Thus, the legal
framework should reinforce the prevention of care problems by giving more
efficient support to carers and permitting legal intervention in the case of
abuse. However, at the same time, the proposed legislation should take into
account the importance of the individual's right to self-determination.
PMID- 28493093
TI - Insights from mathematical modeling for convection-enhanced intraputamenal
delivery of GDNF.
AB - Glial cell line-derived neurotrophic factor (GDNF) is a potential therapy for
Parkinson's disease (PD) promoting survival and functional recovery of
dopaminergic neurons when delivered to the degenerated striatum. To study the
aspects of intraputamenal delivery of GDNF, a mathematical model of recombinant
methionyl human GDNF (r-metHuGDNF) convection in the human putamen has been
developed. The convection-enhanced delivery infusions of r-metHuGDNF were
simulated at rates up to 5 MUL/min. The high-rate infusions (>=1 MUL/min) permit
rapid and uniform distribution of drug with up to 75% of the distribution volume
having a concentration within 5% of the infusate concentration. No relevant
differences in distribution at infusion rates of 3 and 5 MUL/min were found. The
patterns of GDNF distribution were analyzed in relation to the anatomy of the
posterior dorsal putamen, and a cylindrical shape was found to be preferable
considering risks of target overflow. A magnetic resonance (MR) tracer Gd-DTPA
(Magnevist(r)) was evaluated as a surrogate in clinical studies, and the most
accurate prediction of GDNF distribution was calculated immediately after
infusion. The clearance of GDNF from the striatum is confirmed to be slow, with a
half-life of ca. 19 h.
PMID- 28493094
TI - New minimally invasive surgical approach for excision of left atrial myxoma.
AB - A novel minimally invasive technique for left atrial myxoma surgery involving a
combination of mini-sternotomy and restricted left atrial dome incision is
described. Surgery is performed through a mini-J sternotomy at third intercostal
space and a standard aorto-right atrial cannulation. Exposure of cardiac mass is
obtained by a restricted incision of the left atrial dome which provides
excellent view of the entire interatrial septum. Base of the tumor base is
clearly visualized making the en-bloc excision extremely easy. Three cases were
successfully treated with this technique and discharged with mild analgesic
requirements. The limited invasiveness and the avoidance of wide incisions in the
heart chambers are points of strength of this approach and allow to overcome the
limitations of the currently used interatrial groove or transeptal approaches, as
scarce visualization of the septum and site of tumor attachment and risk of
conduction disturbances or traumatic injury to the mass.
PMID- 28493095
TI - Can a Saddle Nose Deformity of Granulomatosis with Polyangiitis be Repaired?
PMID- 28493096
TI - Multiple malignant epithelioid mesotheliomas of the liver and greater omentum: a
case report and review of the literature.
AB - BACKGROUND: Malignant mesothelioma commonly arises from the pleura, but can also
arise from the peritoneum, pericardium, and tunica vaginalis testis. However,
malignant mesothelioma of the liver is extremely rare and coexistence with
malignant mesothelioma of the greater omentum has not been described in the
literature. In this case report, we present a case of multiple malignant
mesothelioma of the liver and greater omentum. CASE PRESENTATION: A 36-year-old
woman was admitted to our hospital for the evaluation of an elastic hard mass in
the right upper abdomen. Abdominal contrast computed tomography showed a cystic
mass measuring 13 * 14 * 11 cm in the right liver lobe with enhanced mural
nodule. Abnormal accumulation was identified in the liver and lower abdominal
area on 18F-fluorodeoxyglucose positron emission tomography. The patient
underwent hepatectomy of the posterior segment and partial resection of the
omentum. The final pathological diagnosis was low-grade multiple malignant
epithelioid mesothelioma based on characteristic immunohistochemical findings. As
of 6 months postoperatively, the patient has shown no disease recurrence.
CONCLUSIONS: We present the first case of a 36-year-old woman with multiple
malignant mesothelioma of the liver and greater omentum.
PMID- 28493097
TI - Gastric adenosquamous carcinoma producing granulocyte-colony stimulating factor:
a case of a rare malignancy.
AB - BACKGROUND: A gastric adenosquamous carcinoma (ASC) that produces granulocyte
colony stimulating factor (G-CSF) is an uncommon malignancy with a poor
prognosis. Due to the rarity of this lesion, a standard treatment for the disease
has not been established. CASE PRESENTATION: We describe a case of a 66-year-old
male with a G-CSF-producing gastric ASC who presented with severe anemia and
leukocytosis. A radical resection was performed, followed by a course of adjuvant
chemotherapy. Histopathologic examination revealed that the tumor consisted of
areas of both squamous cell carcinoma and adenocarcinoma. Immunohistochemical
staining with an anti-G-CSF antibody was also positive. He was started on
adjuvant capecitabine and oxaliplatin (CapeOX) 6 weeks after surgery. The patient
stopped treatment after 3 months due to his own preference. Eight months
following surgery, the patient was found to have diffuse lymph node, liver, and
peritoneal metastases. CONCLUSIONS: G-CSF-producing gastric ASC is a rare and
aggressive tumor. Because patients are usually diagnosed at an advanced stage,
multidisciplinary evaluation and innovative treatments are needed. The rarity of
this disease, with its aggressive features, poses a significant challenge in its
treatment. In this brief case report, we summarize the management and outcomes of
G-CSF-producing gastric ASC.
PMID- 28493098
TI - Personalized Therapeutics and Pharmacogenomics: Integral to Personalized Health
Care.
PMID- 28493099
TI - Anti-Inflammatory Therapeutic Effect of Adiponectin Gene Delivery Using a
Polymeric Carrier in an Acute Lung Injury Model.
AB - PURPOSE: Adiponectin (APN) is an adipokine with anti-inflammatory and
cytoprotective effects. In this study, the therapeutic effect of APN gene
delivery using a polymeric carrier was evaluated in an acute lung injury (ALI)
model. METHODS: Polyethylenimine (2 kDa, PEI2K), PEI25K (25 kDa), polyamidoamine
(generation 2, PAMG2), dexamethasone-conjugated PEI2k (PEI2K-Dexa), and
dexamethasone-conjugated PAMG2 (PAMG2-Dexa) were evaluated in vitro and in vivo
as gene carriers. Formation of plasmid DNA (pDNA)/carrier complexes was confirmed
by gel retardation and heparin competition assays. Delivery efficiency was
measured by a luciferase assay and fluorescence microscopy. In an ALI animal
model, pAPN/carrier complexes were delivered by intratracheal administration.
Therapeutic effects were evaluated by cytokine assays and hematoxylin and eosin
(H&E) staining. RESULTS: Gel retardation assays showed that PEI2K-Dexa and PAMG2
Dexa formed complexes with pDNA. In L2 lung epithelial cells, PAMG2-Dexa yielded
higher transfection efficiency than PEI2K, PAMG2, PEI25K, lipofectamine, and
PEI2K-Dexa. In vivo experiments showed that PAMG2-Dexa delivered DNA more
efficiently to lung tissue than PEI2K-Dexa and PEI25K. Delivery of pAPN/PAMG2
Dexa complexes upregulated APN expression in the lungs of mice with ALI. As a
result, the levels of pro-inflammatory cytokines such as TNF-alpha and IL-1beta
were decreased. H&E staining showed that inflammation in the lungs of mice with
ALI was reduced by delivery of the APN gene. CONCLUSION: Delivery of the APN gene
using PAMG2-Dexa reduced inflammation in the lungs of mice with ALI. The APN gene
could be a useful tool in the development of gene therapy for ALI.
PMID- 28493100
TI - Characterization of Temperature Profiles in Skin and Transdermal Delivery System
When Exposed to Temperature Gradients In Vivo and In Vitro.
AB - PURPOSE: Performance of a transdermal delivery system (TDS) can be affected by
exposure to elevated temperature, which can lead to unintended safety issues.
This study investigated TDS and skin temperatures and their relationship in vivo,
characterized the effective thermal resistance of skin, and identified the in
vitro diffusion cell conditions that would correlate with in vivo observations.
METHODS: Experiments were performed in humans and in Franz diffusion cells with
human cadaver skin to record skin and TDS temperatures at room temperature and
with exposure to a heat flux. Skin temperatures were regulated with two methods:
a heating lamp in vivo and in vitro, or thermostatic control of the receiver
chamber in vitro. RESULTS: In vivo basal skin temperatures beneath TDS at
different anatomical sites were not statistically different. The maximum
tolerable skin surface temperature was approximately 42-43 degrees C in vivo. The
temperature difference between skin surface and TDS surface increased with
increasing temperature, or with increasing TDS thermal resistance in vivo and in
vitro. CONCLUSIONS: Based on the effective thermal resistance of skin in vivo and
in vitro, the heating lamp method is an adequate in vitro method. However, the in
vitro-in vivo correlation of temperature could be affected by the thermal
boundary layer in the receiver chamber.
PMID- 28493101
TI - The German East-West Mortality Difference: Two Crossovers Driven by Smoking.
AB - Before the fall of the Berlin Wall, mortality was considerably higher in the
former East Germany than in West Germany. The gap narrowed rapidly after German
reunification. The convergence was particularly strong for women, to the point
that Eastern women aged 50-69 now have lower mortality despite lower incomes and
worse overall living conditions. Prior research has shown that lower smoking
rates among East German female cohorts born in the 1940s and 1950s were a major
contributor to this crossover. However, after 1990, smoking behavior changed
dramatically, with higher smoking intensity observed among women in the eastern
part of Germany. We forecast the impact of this changing smoking behavior on East
West mortality differences and find that the higher smoking rates among younger
East German cohorts will reverse their contemporary mortality advantage.
Mortality forecasting methods that do not account for smoking would, perhaps
misleadingly, forecast a growing mortality advantage for East German women.
Experience from other countries shows that smoking can be effectively reduced by
strict anti-smoking policies. Instead, East Germany is becoming an example
warning of the consequences of weakening anti-smoking policies and changing
behavioral norms.
PMID- 28493102
TI - MEN2 Syndrome-Related Medullary Thyroid Carcinoma with Focal Tyrosine Hydroxylase
Expression: Does It Represent a Hybrid Cellular Phenotype or Functional State of
Tumor Cells?
PMID- 28493103
TI - Cellulose Derivatives Enhanced Stability of Alginate-Based Beads Loaded with
Lactobacillus plantarum LAB12 against Low pH, High Temperature and Prolonged
Storage.
AB - The susceptibility of probiotics to low pH and high temperature has limited their
use as nutraceuticals. In this study, enhanced protection of probiotics via
microencapsulation was achieved. Lactobacillus plantarum LAB12 were immobilised
within polymeric matrix comprised of alginate (Alg) with supplementation of
cellulose derivatives (methylcellulose (MC), sodium carboxymethyl cellulose
(NaCMC) or hydroxypropyl methylcellulose (HPMC)). L. plantarum LAB12 encapsulated
in Alg-HPMC(1.0) and Alg-MC(1.0) elicited improved survivability (91%) in
simulated gastric conditions and facilitated maximal release (~100%) in simulated
intestinal condition. Alg-HPMC(1.0) and Alg-MC(1.0) significantly reduced (P <
0.05) the viability loss of LAB12 (viability loss <7%) when compared to Alg alone
(viability loss <13%) under extreme temperatures (75 and 90 degrees C). Four
week storage of encapsulated LAB12 at 4 degrees C yielded viable counts >7 log
CFU g-1. Alg-MC and Alg-HPMC improved the survival of LAB12 against simulated
gastric condition (9.24 and 9.55 log CFU g-1, respectively), temperature up to 90
degrees C (9.54 and 9.86 log CFU g-1, respectively) and 4-week of storage at 4
degrees C (8.61 and 9.23 log CFU g-1, respectively) with sustained release of
probiotic in intestinal condition (>9 log CFU g-1). These findings strongly
suggest the potential of cellulose derivatives supplemented Alg bead as
protective micro-transport for probiotic strains. They can be safely incorporated
into new functional food or nutraceutical products.
PMID- 28493104
TI - Hypomyelinating leukodystrophy associated with a deleterious mutation in the ATRN
gene.
AB - Hypomyelinating leukodystrophies are a group of neurodevelopmental disorders that
affect proper formation of the myelin sheath in the central nervous system. They
are characterized by developmental delay, hypotonia, spasticity, and variable
intellectual disability. We used whole exome analysis to study the molecular
basis of hypomyelinating leukodystrophy in two sibs from a consanguineous family.
A homozygous mutation, c.3068+5G>A, was identified in the ATRN gene, with the
consequent insertion of an intronic sequence into the patients' cDNA and a
predicted premature termination of the ATRN polypeptide. ATRN encodes Attractin,
which was previously shown to play a critical role in central myelination.
Several spontaneous ATRN rodent mutants exhibited impaired myelination which was
attributed to oxidative stress and accelerated apoptosis. ATRN can now be added
to the growing list of genes associated with hypomyelinating leukodystrophy. The
disease seems to be confined to the CNS; however, given the young age of our
patients, longer follow-up may be required.
PMID- 28493105
TI - Association between cardiovascular disease risk scores and subclinical
atherosclerosis prevalence in non-elderly adult patients from Argentina.
AB - The goal of our study was to use statistical analysis to try to associate
cardiovascular disease (CVD) risk scores and the observed prevalence of
subclinical atherosclerosis (SA) in a non-elderly adult local population. An
observational cross-sectional study was carried out (143 male and 131 female) on
non-elderly adults (20-59 years). CVD risk scores included Framingham Risk Scores
for 10-year hard (FRS 10 H), 30-year lipid hard or CVD (FRS 30 L H or FRS 30 L
CVD), 30 year-body mass index hard or CVD (FRS 30 BMI H or FRS 30 BMI CVD) and
Pooled Cohort Risk Equations for either 10 years (PCE 10) or lifetime (PCE LT).
The Carotid Ultrasound (CU) study was performed and the Coronary Artery Calcium
(CAC) score were obtained to assess SA. The Receiving Operating Characteristic
(ROC) curve analysis followed by Youden's index was used to evaluate and adjust
the stratification of CVD risk scores. SA was detected in 32.4% of individuals.
The risk scores that showed the biggest areas under the ROC curve were FRS 30 L
(H and CVD). When the cut-off values for these CVD risk scores were adjusted, the
FRS 30 L H increased the negative predictive value for the low risk group from
87.7 to 97.0% and the FRS 30 L CVD increased the positive predictive values for
the high risk group from 69.7 to 85.7%. The CVD risk stratification of non
elderly adults using FRS 30 L H and FRS 30 L CVD may be a useful tool for
selecting candidate patients for diagnostic imaging studies that assess their SA
prevalence.
PMID- 28493106
TI - Human classifier: Observers can deduce task solely from eye movements.
AB - Computer classifiers have been successful at classifying various tasks using eye
movement statistics. However, the question of human classification of task from
eye movements has rarely been studied. Across two experiments, we examined
whether humans could classify task based solely on the eye movements of other
individuals. In Experiment 1, human classifiers were shown one of three sets of
eye movements: Fixations, which were displayed as blue circles, with larger
circles meaning longer fixation durations; Scanpaths, which were displayed as
yellow arrows; and Videos, in which a neon green dot moved around the screen.
There was an additional Scene manipulation in which eye movement properties were
displayed either on the original scene where the task (Search, Memory, or Rating)
was performed or on a black background in which no scene information was
available. Experiment 2 used similar methods but only displayed Fixations and
Videos with the same Scene manipulation. The results of both experiments showed
successful classification of Search. Interestingly, Search was best classified in
the absence of the original scene, particularly in the Fixation condition. Memory
also was classified above chance with the strongest classification occurring with
Videos in the presence of the scene. Additional analyses on the pattern of
correct responses in these two conditions demonstrated which eye movement
properties successful classifiers were using. These findings demonstrate
conditions under which humans can extract information from eye movement
characteristics in addition to providing insight into the relative
success/failure of previous computer classifiers.
PMID- 28493107
TI - Beyond immunomodulation: The regenerative role for regulatory T cells in central
nervous system remyelination.
AB - Central nervous system regeneration after injury can occur in the form of
remyelination, the reinstatement of myelin around axons which restores axon
health and function. However, remyelination often fails in chronic neurological
diseases, such as progressive multiple sclerosis. The lack of currently approved
pro-remyelination therapies highlights the need to elucidate the cellular and
molecular mechanisms underpinning this regenerative process. Whereas some T
lymphocyte subsets such as Th1 and Th17 are implicated in inducing myelin injury,
a recent study by Dombrowski et al. reveals a novel role for regulatory T cells
(Tregs) in directly driving remyelination, independent of immunomodulation (Nat
Neurosci doi: 10.1038/nn.4528 2017)(Dombrowski et al., 2017). This study is
summarized in this Bits and Bytes.
PMID- 28493108
TI - Percutaneous Septectomy in Chronic Dissection with Abdominal Aortic Aneurysm
Creates Uniluminal Neck for EVAR.
AB - PURPOSE: The intent of this report is to describe the technical details and
rationale of endovascular septectomy using a wire saw maneuver in cases of
chronic aortic dissection and associated infra-renal aortic aneurysm to allow
standard endovascular abdominal aortic graft placement; preliminary clinical
experience is also retrospectively reviewed. MATERIALS AND METHODS: Between June
2013 and June 2016, four consecutive patients (mean age 55.3 years; range 52-58
years) with chronic type B aortic dissection and isolated infra-renal abdominal
aortic aneurysm (AAA) underwent endovascular aneurysm repair (EVAR) following
guidewire septectomy to create a suitable proximal aortic landing zone. Technical
success was evaluated by angiography performed at the end of the procedure.
Procedural safety was determined by assessing any major adverse events through 30
days of follow-up. Endoleaks and longer-term efficacy were evaluated. RESULTS:
Four patients with chronic aortic dissections had associated AAA with a mean
maximum diameter of 60 +/- 13 mm (range 50-77 mm). All underwent guidewire saw
septectomy to facilitate EVAR. Following successful septectomy, standard
abdominal bifurcated endografts were implanted uneventfully. No major adverse
events and no endoleaks were noted on CT angiographic examinations through 30
days following the procedure. Also, no rupture, re-intervention or endoleak has
been noted during follow-up at a mean of 21.8 +/- 15 months (range 4-39 months).
CONCLUSIONS: Guidewire saw septectomy is a technique that has the potential to
create an anatomically suitable proximal neck for successful EVAR management of
AAA in select patients with associated chronic aortic dissection.
PMID- 28493109
TI - Effectiveness of the Conservative Therapy for Symptomatic Isolated Celiac Artery
Dissection.
AB - OBJECTIVE: To investigate the effectiveness of the conservative therapy for
symptomatic isolated celiac artery dissection (ICAD). METHODS: Patients with
symptomatic ICAD diagnosed on CT between February 2006 and June 2016 at three
institutions were included. RESULTS: During the study period, a total of 24
patients (22 men, 2 women) were included in this retrospective study. Patients
most commonly presented with epigastric pain (n = 21) or back pain (n = 3).
Initial CT findings included celiac arterial calcification (n = 3); compression
of the true lumen (n = 24), including stenosis of the true lumen <50% (n = 14) or
>=50% (n = 10); completely thrombosed (n = 11) or partially thrombosed (n = 5)
false lumen; no thrombosis of the false lumen but presence of dissecting aneurysm
(n = 8); and dissection extending to the common hepatic (n = 1) or splenic (n =
6) artery. Twenty-three patients recovered after conservative treatment, and one
patient who failed conservative treatment recovered after surgical therapy. Of
the 23 patients who received conservative treatment, complete or partial
remodeling of ICAD was achieved in 18 (78.3%) and 5 (21.7%) patients during 22.1
+/- 13.3 months of follow-up. CONCLUSIONS: Conservative treatment can be applied
successfully in most patients with symptomatic ICAD. Most cases of symptomatic
ICAD resolve spontaneously within 2 years.
PMID- 28493110
TI - BEM-based simulation of lung respiratory deformation for CT-guided biopsy.
AB - PURPOSE: Accurate and real-time prediction of the lung and lung tumor deformation
during respiration are important considerations when performing a peripheral
biopsy procedure. However, most existing work focused on offline whole lung
simulation using 4D image data, which is not applicable in real-time image-guided
biopsy with limited image resources. In this paper, we propose a patient-specific
biomechanical model based on the boundary element method (BEM) computed from CT
images to estimate the respiration motion of local target lesion region, vessel
tree and lung surface for the real-time biopsy guidance. METHODS: This approach
applies pre-computation of various BEM parameters to facilitate the requirement
for real-time lung motion simulation. The resulting boundary condition at end
inspiratory phase is obtained using a nonparametric discrete registration with
convex optimization, and the simulation of the internal tissue is achieved by
applying a tetrahedron-based interpolation method depend on expert-determined
feature points on the vessel tree model. A reference needle is tracked to update
the simulated lung motion during biopsy guidance. RESULTS: We evaluate the model
by applying it for respiratory motion estimations of ten patients. The average
symmetric surface distance (ASSD) and the mean target registration error (TRE)
are employed to evaluate the proposed model. Results reveal that it is possible
to predict the lung motion with ASSD of [Formula: see text] mm and a mean TRE of
[Formula: see text] mm at largest over the entire respiratory cycle. In the CT
/electromagnetic-guided biopsy experiment, the whole process was assisted by our
BEM model and final puncture errors in two studies were 3.1 and 2.0 mm,
respectively. CONCLUSION: The experiment results reveal that both the accuracy of
simulation and real-time performance meet the demands of clinical biopsy
guidance.
PMID- 28493111
TI - Parasympathetic Regulation and Inhibitory Control Predict the Development of
Externalizing Problems in Early Childhood.
AB - The current report examined the longitudinal relations between cognitive self
regulation, physiological self-regulation, and externalizing problems. At age 4
(n = 98; 49 girls) and 6 (n = 87; 42 girls), children completed the Day-Night
task, which taps the inhibitory control dimension of executive function. During
the task, cardiac activity was measured and respiratory sinus arrhythmia (RSA)
was derived as an index of parasympathetic activity. Mothers reported on
externalizing problems. A cross-lagged path model was used to estimate
longitudinal predictions while controlling for stability in all constructs over
time. Earlier inhibitory control negatively predicted later externalizing
problems, but not vice versa. However, RSA reactivity moderated this link; better
inhibitory control predicted fewer externalizing problems only when reactivity to
the Day-Night task ranged from mild RSA suppression to RSA augmentation.
Externalizing problems at 6 years were highest among preschoolers who augmented
RSA but showed poor inhibitory control performance, suggesting that risk for
psychopathology may be better delineated by viewing self-regulation from an
integrated, multi-system perspective.
PMID- 28493112
TI - The teaching of management of the pulp in primary molars across Europe.
AB - AIM: To determine which methods of primary pulp therapy are currently being
taught in European dental schools. METHODS: An online survey tool was employed to
send questionnaires to paediatric dentistry departments of 202 European dental
schools. Email addresses were obtained from the European Academy of Paediatric
Dentistry and questionnaires were sent to one member of each department in
December 2014. The survey included questions on treatment choices and clinical
scenarios where respondents indicated how they would advise students to proceed,
given a particular case. RESULTS: Fifty-one responses from 22 different countries
were obtained. Eleven schools reported that they taught only undergraduate
students, 4 only postgraduates and 36 taught both. Forty-three schools taught
indirect pulp capping, the most popular material being calcium hydroxide; 26
taught direct pulp capping, mostly using mineral trioxide aggregate (MTA).
Teaching of pulpotomy was widespread across Europe, with MTA being the most
popular material, taught in 37 schools, followed by ferric sulphate, in 29.
Formocresol, however, was still being taught in 12 dental schools. Responses to
the clinical scenarios were mostly in accordance with previously selected
choices. CONCLUSIONS: This study had a representative sample, showing a wide
variation in primary pulp therapies taught in Europe. Comparison with previous
studies shows new trends in taught therapies, possibly driven by recent research
in primary pulp management and the development of new materials.
PMID- 28493113
TI - [Results of scrotal orchidopexie without ligation of an open processus].
PMID- 28493114
TI - [Management of multiresistant bacteria in urology].
AB - Contamination and infection with extensive drug resistant (XDR) bacteria are
increasing in urology with the exception of methicillin resistant Staphylococcus
aureus (MRSA) (stabilization). They often lead to logistic and therapeutical
problems. Only 30-50% of XDR cases are of exogenous origin. To slow this trend,
screening, hygiene programs, isolation, decontamination, targeted therapy of
symptomatic infections, education programs, and success controls should be
applied. Furthermore, all regulatory and legal instructions should be followed.
Local hygiene networks help to find apt measures for XDR control. It is important
to balance hygiene measures against hygiene hysteria. To prepare urological
instruments, a local instrument preparation plan that takes into consideration
all legal instructions should be followed. The efforts in health system general
prophylactic measures should be supported. Only with consistent implementation in
all areas of daily life (health care, local environment, animal husbandry, and
soil contaminated within the framework of animal husbandry) can a substantial
reduction of XDR bacteria be achieved in the long term.
PMID- 28493115
TI - Cardiovascular Disease & Cancer Risk Among South Asians: Impact of Sociocultural
Influences on Lifestyle and Behavior.
AB - A comprehensive literature review revealed cultural beliefs, societal
obligations, and gender roles within the South Asian community to be indirect
contributors to the health of South Asian immigrants (SAIs). Health professionals
need to increase their work with SAI communities to change less beneficial
cultural elements such as misconceptions about health and exercise, and lack of
communication when using alternative medicines. Community engaged efforts and
continuing medical education are both needed to improve the health of the South
Asian immigrant population in a culturally appropriate manner.
PMID- 28493116
TI - General and Ethnic-Biased Bullying Among Latino Students: Exploring Risks of
Depression, Suicidal Ideation, and Substance Use.
AB - Using a cross-sectional sample of 534 Latino students from middle and high
schools in a large North Carolina school district, we examined the relation of
general and ethnic-biased bullying to depression and the indirect pathways
through depression to suicidal ideation and substance use outcomes. A structural
equation model tested the direct and indirect paths. The final model fit was
excellent, chi2(90) = 127.6, p = .0056, RMSEA = 0.028, CFI = 0.974, TLI = 0.961.
Ethnic-biased and verbal or relational bullying had a direct effect on
depression, but general and physical bullying did not. Indirect effects through
depression were found for ethnic-biased and verbal or relational bullying in
relation to suicidal ideation, alcohol, and illicit drug use. Child nativity was
marginally associated with ethnic-biased bullying, indicating foreign-born
students may experience greater ethnic-biased bullying. Implications for future
research and bullying prevention are discussed.
PMID- 28493117
TI - Erratum to: Polar localization of MreB actin is inhibited by anionic
phospholipids in the rod-shaped bacterium Escherichia coli.
PMID- 28493120
TI - Strategies and Considerations for Improving Expression of "Difficult to Express"
Proteins in CHO Cells.
AB - Despite substantial advances in the field of mammalian expression, there are
still proteins that are characterized as difficult to express. Determining the
expression bottleneck requires troubleshooting techniques specific for the given
molecule and host. The complex array of intracellular processes involved in
protein expression includes transcription, protein folding, post-translation
processing, and secretion. Challenges in any of these steps could result in low
protein expression, while the inherent properties of the molecule itself may
limit its production via mechanisms such as cytotoxicity or inherent instability.
Strategies to identify the rate-limiting step and subsequently improve expression
and production are discussed here.
PMID- 28493119
TI - CO2 sensing in fungi: at the heart of metabolic signaling.
AB - Adaptation to the changing environmental CO2 levels is essential for all living
cells. In particular, microorganisms colonizing and infecting the human body are
exposed to highly variable concentrations, ranging from atmospheric 0.04 to 5%
and more in blood and specific host niches. Carbonic anhydrases are highly
conserved metalloenzymes that enable fixation of CO2 by its conversion into
bicarbonate. This process is not only crucial to ensure the supply of adequate
carbon amounts for cellular metabolism, but also contributes to several signaling
processes in fungi, including morphology and communication. The fungal specific
carbonic anhydrase gene NCE103 is transcribed in response to CO2 availability. As
recently shown, this regulation relies on the ATF/CREB transcription factor Cst6
and the AGC family protein kinase Sch9. Here, we review the regulatory mechanisms
which control NCE103 expression in the model organism Saccharomyces cerevisiae
and the pathogenic yeasts Candida albicans and Candida glabrata and discuss which
additional factors might contribute in this novel CO2 sensing cascade.
PMID- 28493121
TI - Glycoengineering of CHO Cells to Improve Product Quality.
AB - Chinese hamster ovary (CHO) cells represent the predominant platform in
biopharmaceutical industry for the production of recombinant biotherapeutic
proteins, especially glycoproteins. These glycoproteins include oligosaccharide
or glycan attachments that represent one of the principal components dictating
product quality. Especially important are the N-glycan attachments present on
many recombinant glycoproteins of commercial interest. Furthermore, altering the
glycan composition can be used to modulate the production quality of a
recombinant biotherapeutic from CHO and other mammalian hosts. This review first
describes the glycosylation network in mammalian cells and compares the
glycosylation patterns between CHO and human cells. Next genetic strategies used
in CHO cells to modulate the sialylation patterns through overexpression of
sialyltransfereases and other glycosyltransferases are summarized. In addition,
other approaches to alter sialylation including manipulation of sialic acid
biosynthetic pathways and inhibition of sialidases are described. Finally, this
review also covers other strategies such as the glycosylation site insertion and
manipulation of glycan heterogeneity to produce desired glycoforms for diverse
biotechnology applications.
PMID- 28493118
TI - Position matters: multiple functions of LINC-dependent chromosome positioning
during meiosis.
AB - Chromosome positioning is crucial for multiple chromosomal events, including DNA
replication, repair, and recombination. The linker of nucleoskeleton and
cytoskeleton (LINC) complexes, which consist of conserved nuclear membrane
proteins, were shown to control chromosome positioning and facilitate various
biological processes by interacting with the cytoskeleton. However, the precise
functions and regulation of LINC-dependent chromosome positioning are not fully
understood. During meiosis, the LINC complexes induce clustering of telomeres,
forming the bouquet chromosome arrangement, which promotes homologous chromosome
pairing. In fission yeast, the bouquet forms through LINC-dependent clustering of
telomeres at the spindle pole body (SPB, the centrosome equivalent in fungi) and
detachment of centromeres from the SPB-localized LINC. It was recently found
that, in fission yeast, the bouquet contributes to formation of the spindle and
meiotic centromeres, in addition to homologous chromosome pairing, and that
centromere detachment is linked to telomere clustering, which is crucial for
proper spindle formation. Here, we summarize these findings and show that the
bouquet chromosome arrangement also contributes to nuclear fusion during
karyogamy. The available evidence suggests that these functions are universal
among eukaryotes. The findings demonstrate that LINC-dependent chromosome
positioning performs multiple functions and controls non-chromosomal as well as
chromosomal events, and that the chromosome positioning is stringently regulated
for its functions. Thus, chromosome positioning plays a much broader role and is
more strictly regulated than previously thought.
PMID- 28493122
TI - Large-Scale Transient Transfection of Chinese Hamster Ovary Cells in Suspension.
AB - We describe a one-liter transfection of suspension-adapted Chinese hamster ovary
(CHO-DG44) cells using polyethyleneimine (PEI) for DNA delivery. The method
involves transfection at a high cell density (5 * 106 cells/mL) by direct
addition of plasmid DNA (pDNA) and PEI to the culture and subsequent incubation
at 31 degrees C with agitation by orbital shaking. We also describe an
alternative method in which 90% of the pDNA is replaced by nonspecific (filler)
DNA, and the production phase is performed at 31 degrees C in the presence of
0.25% N, N-dimethylacetamide (DMA).
PMID- 28493123
TI - Cloning of Single-Chain Antibody Variants by Overlap-Extension PCR for Evaluation
of Antibody Expression in Transient Gene Expression.
AB - Single-chain fragment variable-fragment crystallizable antibody constructs (scFv
Fc) are homodimeric proteins representing valuable alternatives to
heterotetrameric full-length IgG molecules to study protein properties and
product-dependent cellular behavior. In contrast to naturally occurring
antibodies, these artificial molecules are assembled from functional antibody
domains to reduce molecule complexity and enhance antibody expression levels. The
scFv-Fc format retains critical antibody functions such as antigen binding
affinity and antibody effector functions. Here, we present a protocol to convert
the full-length anti-HIV-1 IgG1 antibody 2F5 into a scFv-Fc construct. Variable
and constant regions are amplified by conventional PCR reactions and assembled by
a single overlap-extension PCR reaction. The amplified product is then cloned
into a mammalian expression vector suitable for high-titer transient gene
expression. This workflow can be applied to any antibody sequence by adapting the
specific primer sequences to the antibody of choice.
PMID- 28493124
TI - Anti-Apoptosis Engineering for Improved Protein Production from CHO Cells.
AB - Improving the time integral of viable cell concentration by overcoming cell
death, namely apoptosis, is one of the widely used strategies for efficient
production of therapeutic proteins. By establishing stable cell lines that
overexpress anti-apoptotic genes or down-regulate pro-apoptotic genes, the final
product yields can be enhanced as cells become more resistance to environmental
stresses. From the selection of high-expressing clones to verification of anti
apoptotic activity, the method to construct a stable anti-apoptotic cell line is
discussed in this chapter.
PMID- 28493125
TI - Conditional Knockdown of Endogenous MicroRNAs in CHO Cells Using TET-ON-SanDI
Sponge Vectors.
AB - MicroRNAs (miRNAs) are small, noncoding RNAs of about 22 nucleotides in length
and have proven to be useful targets for genetic modifications for desirable
phenotype in the biotech industry. The use of constitutively expressed "miRNA
sponge" vectors in which multiple, tandem miRNA binding sites containing
transcripts are transcriptionally regulated by a constitutive promoter for down
regulating the levels of endogenous microRNAs in Chinese hamster ovary (CHO)
cells has shown to be more advantageous than using synthetic antisense
oligonucleotides. The application of miRNA sponges in biotechnological processes,
however, could be more effective, if expression of miRNA sponges could be tuned.
In this chapter, we present a method for the generation of stable CHO cell lines
expressing a TET-ON-SanDI-miRNA-sponge that is in theory expressed only in the
presence of an inducer.
PMID- 28493126
TI - Application of CRISPR/Cas9 Genome Editing to Improve Recombinant Protein
Production in CHO Cells.
AB - Genome editing has become an increasingly important aspect of Chinese Hamster
Ovary (CHO ) cell line engineering for improving production of recombinant
protein therapeutics. Currently, the focus is directed toward expanding the
product diversity, controlling and improving product quality and yields. In this
chapter, we present our protocol on how to use the genome editing tool Clustered
Regularly Interspaced Short Palindromic Repeat (CRISPR)/CRISPR-associated protein
9 (Cas9) to knockout engineering target genes in CHO cells. As an example, we
refer to the glutamine synthetase (GS)-encoding gene as the knockout target gene,
a knockout that increases the selection efficiency of the GS-mediated gene
amplification system.
PMID- 28493127
TI - Improved CHO Cell Line Stability and Recombinant Protein Expression During Long
Term Culture.
AB - Therapeutic proteins require proper folding and posttranslational modifications
to be effective and biologically active. Chinese hamster ovary (CHO) cells are by
far the most frequently used host for commercial production of therapeutic
proteins. However, an unpredictable decrease in protein productivity during the
time required for scale up impairs process yields, time, finance, and regulatory
approval for the desired product. Therefore, it is important to assess cell lines
at stages throughout the period of long-term culture in terms of productivity and
various molecular parameters including plasmid and mRNA copy numbers and location
of the plasmid on the host cell chromosome. Here, we describe methods, which are
frequently used to analyze stability of the recombinant CHO cells over long-term
culture. These procedures include the following; western blotting, ELISA to
evaluate protein production, real-time PCR to analyze plasmid and mRNA copy
numbers, and fluorescent in situ hybridization (FISH) to assess the location of
the inserted plasmid on host cell chromosomes.
PMID- 28493128
TI - Selection of High-Producing Clones Using FACS for CHO Cell Line Development.
AB - Cell line development aims to generate and select clones with desirable
characteristics. One of the most important parameters for biopharmaceutical cell
selection is cell-specific productivity (Qp) or the quantity of product produced
per cell per day. Fluorescence-activated cell sorting (FACS) is a powerful, high
throughput technique that facilitates multiparametric characterization and
isolation of individual cell clones from heterogeneous populations. Here, we
describe a FACS-based method for section of high-producing CHO cell clones.
PMID- 28493129
TI - The 'Omics Revolution in CHO Biology: Roadmap to Improved CHO Productivity.
AB - Increased understanding of Chinese hamster ovary (CHO) cell physiology has been
ushered in upon availability of the parental CHO-K1 cell line genome. Free and
openly accessible sequence information has complemented transcriptomic and
proteomic studies. The previous decade has also seen an increase in sensitivity
and accuracy of proteomic methods due to technology development. In this genomic
era, high-throughput screening methods, sophisticated informatic tools, and
models continually drive major innovations in cell line development and process
engineering. This review describes the various achievements in 'omics techniques
and their application to improve recombinant protein expression from CHO cell
lines.
PMID- 28493130
TI - A Bioinformatics Pipeline for the Identification of CHO Cell Differential Gene
Expression from RNA-Seq Data.
AB - In recent years, the publication of genome sequences for the Chinese hamster and
Chinese hamster ovary (CHO) cell lines has facilitated study of these
biopharmaceutical cell factories with unprecedented resolution. Our understanding
of the CHO cell transcriptome, in particular, has rapidly advanced through the
application of next-generation sequencing (NGS) technology to characterize RNA
expression (RNA-Seq). In this chapter, we present a computational pipeline for
the analysis of CHO cell RNA-Seq data from the Illumina platform to identify
differentially expressed genes. The example data and bioinformatics workflow
required to run this analysis are freely available at
www.cgcdb.org/rnaseq_analysis_protocol.html .
PMID- 28493131
TI - Filter-Aided Sample Preparation (FASP) for Improved Proteome Analysis of
Recombinant Chinese Hamster Ovary Cells.
AB - Chinese hamster ovary (CHO) cells are the most commonly used mammalian host cell
line for biopharmaceutical production because of their ability to correctly fold
and posttranslationally modify recombinant proteins that are compatible with
human use. Proteomics, along with other 'omic platforms, are being used to
understand the biology of CHO cells with the ultimate aim of enhancing CHO cell
factories for more efficient production of biopharmaceuticals. In this chapter,
we will describe an efficient protocol called Filter Aided Sample Preparation
(FASP) for the extraction of proteins from CHO cells for proteomic studies. FASP
uses a common ultrafiltration device whereby the membrane pores are small enough
to allow contaminating detergents to pass through, while proteins are too large
and are retained and concentrated in the filter unit. This method of sample
preparation and protein digestion is universally applicable and can be easily
employed in any proteomics facilities as standard everyday laboratory reagents
and equipment are used.
PMID- 28493132
TI - Phosphopeptide Enrichment and LC-MS/MS Analysis to Study the Phosphoproteome of
Recombinant Chinese Hamster Ovary Cells.
AB - The reversible phosphorylation of proteins on serine, threonine, and tyrosine
residues is one of the most important post-translational modifications that
regulates many biological processes. The phosphoproteome has not been studied in
any great detail in recombinant Chinese hamster ovary (CHO) cells to date despite
phosphorylation playing a crucial role in regulating many molecular and cellular
processes relevant to bioprocess phenotypes including, for example,
transcription, translation, growth, apoptosis, and signal transduction. In this
chapter, we provide a protocol for the phosphoproteomic analysis of Chinese
hamster ovary cells using phosphopeptide enrichment with metal oxide affinity
chromatography (MOAC) and immobilized metal affinity chromatography (IMAC)
techniques, followed by site-specific identification of phosphorylated residues
using LC-MS (MS2 and MS3) strategies.
PMID- 28493133
TI - Engineer Medium and Feed for Modulating N-Glycosylation of Recombinant Protein
Production in CHO Cell Culture.
AB - Chinese hamster ovary (CHO) cells have become the primary expression system for
the production of complex recombinant proteins due to their long-term success in
industrial scale production and generating appropriate protein N-glycans similar
to that of humans. Control and optimization of protein N-glycosylation is
crucial, as the structure of N-glycans can largely influence both biological and
physicochemical properties of recombinant proteins. Protein N-glycosylation in
CHO cell culture can be controlled and tuned by engineering medium, feed, culture
process, as well as genetic elements of the cell. In this chapter, we will focus
on how to carry out experiments for N-glycosylation modulation through medium and
feed optimization. The workflow and typical methods involved in the experiment
process will be presented.
PMID- 28493134
TI - Glycosylation Analysis of Therapeutic Glycoproteins Produced in CHO Cells.
AB - In the last decades, the number of approved therapeutic proteins drugs is
increasing exponentially and a large number of new therapeutic entities are
progressing through clinical trials, solidifying biologics as the most promising
class of pharmaceuticals on the market. Several cell lines are available for
biopharmaceutical processes but mammalian cells are preferred since they give
fewer problems for immunogenicity as they produce human-like post-translational
modifications (PTMs). Glycosylation is the most common and complex (for both
bioprocess engineering and quality control) of these modifications. Obtaining the
desired glycosylation pattern is crucial for therapeutic proteins as it can
impact significantly stability, half-life and safety as well as driving molecular
processes, modifying the way drug interacts with patients' cells. As a
consequence, glycosylation (like other PTMs) needs to be regulated and accurately
analyzed during biopharmaceutical production. Herein we describe and discuss the
analytical approaches for glycosylation analysis of therapeutic glycoproteins
produced in CHO (Chinese Hamster Ovary) cells. This chapter will describe
glycoprotein purification after separation from producing cell lines, N-glycan
release and their variants fine structural characterization through mass
spectrometry techniques.
PMID- 28493135
TI - Characterization of Host Cell Proteins (HCPs) in CHO Cell Bioprocesses.
AB - Host cell protein content during bioprocessing of biotherapeutic proteins
generated from cultured Chinese hamster ovary (CHO) cells is typically measured
using immunological and gel-based methods. Estimation of HCP concentration is
usually undertaken using Enzyme-Linked ImmunoSorbent Assays (ELISA), while
estimation of HCP clearance/presence can be achieved by comparing 2D-PAGE images
of samples and by undertaking western blotting of 2D-PAGE analyzed samples. Here,
we describe the analyses of HCP content using these methodologies.
PMID- 28493136
TI - Risk factors for cardiovascular disease in subclinical hypothyroidism.
AB - Subclinical hypothyroidism (SH), defined as an increased serum thyrotropin (TSH)
level and normal plasma-free thyroid hormones' concentrations, is common in the
general population, in particular, among elderly women. Its prevalence ranges
from 4 to 15% and up to 20% among females aged > 60 year. Although SH has been
associated with atherosclerotic cardiovascular disease (CVD), it is acknowledged
that the high prevalence of dyslipidemia in elderly people is considered a common
biochemical condition. Therefore, whether SH is associated with a higher risk for
CVD is still controversial. At the moment, no consensus exists on the clinical
significance and treatment of the mild form of thyroid failure, although
available data suggest that only patients with plasma TSH levels above 10 mU/L
may have an increased risk of CVD. However, treatment of SH in older individual
requires special consideration with regard to thyroid hormone replacement therapy
and expected clinical outcomes, since the increase of TSH observed in this
population may represent a physiological process. It is likely that age affects
TSH levels, and some studies suggest that modified reference limits for elderly
populations should be considered in the diagnosis of mild thyroid failure.
PMID- 28493137
TI - Effective dose rate coefficients for exposure to contaminated soil.
AB - The Oak Ridge National Laboratory Center for Radiation Protection Knowledge has
undertaken calculations related to various environmental exposure scenarios. A
previous paper reported the results for submersion in radioactive air and
immersion in water using age-specific mathematical phantoms. This paper presents
age-specific effective dose rate coefficients derived using stylized mathematical
phantoms for exposure to contaminated soils. Dose rate coefficients for photon,
electron, and positrons of discrete energies were calculated and folded with
emissions of 1252 radionuclides addressed in ICRP Publication 107 to determine
equivalent and effective dose rate coefficients. The MCNP6 radiation transport
code was used for organ dose rate calculations for photons and the contribution
of electrons to skin dose rate was derived using point-kernels. Bremsstrahlung
and annihilation photons of positron emission were evaluated as discrete photons.
The coefficients calculated in this work compare favorably to those reported in
the US Federal Guidance Report 12 as well as by other authors who employed voxel
phantoms for similar exposure scenarios.
PMID- 28493138
TI - Effect of Light/Dark Regimens on Hydrogen Production by Tetraselmis
subcordiformis Coupled with an Alkaline Fuel Cell System.
AB - To improve the photoproduction of hydrogen (H2) by a green algae-based system,
the effect of light/dark regimens on H2 photoproduction regulated by carbonyl
cyanide m-chlorophenylhydrazone (CCCP) was investigated. A fuel cell was
integrated into a photobioreactor to allow online monitoring of the H2 evolution
rate and decrease potential H2 feedback inhibition by consuming the generated H2
in situ. During the first 15 h of H2 evolution, the system was subjected to dark
treatment after initial light illumination (L/D = 6/9 h, 9/6 h, and 12/3 h).
After the dark period, all systems were again exposed to light illumination until
H2 evolution stopped. Two peaks were observed in the H2 evolution rate under all
three light/dark regimens. Additionally, a high H2 yield of 126 +/- 10 mL L-1 was
achieved using a light/dark regimen of L 9 h/D 6 h/L until H2 production ceased,
which was 1.6 times higher than that obtained under continuous illumination. H2
production was accompanied by some physiological and morphological changes in the
cells. The results indicated that light/dark regimens improved the duration and
yield of H2 photoproduction by the CCCP-regulated process of Tetraselmis
subcordiformis.
PMID- 28493139
TI - [Lipedema: up-to-date of a long forgotten disease].
AB - Lipedema is a chronic disorder of subcutaneous adipose tissue of unknown etiology
not uncommon among post-puberty women. The disease has a negative impact on self
esteem, mobility, and quality of life. Lipedema is characterized by symmetrical,
disfiguring hyperplastic adipose tissue combined with bruising and pain.
Untreated lipedema fosters osteoarthritis, secondary lymphedema, limited
mobility, and psychosocial stigmatization. Treatment consists of conservative
complex decongestive therapy and surgery by microcannular tumescent liposuction.
Liposuction is the only available treatment capable to reduce the pathological
adipose tissue durable and to prevent complications.
PMID- 28493140
TI - [Health disorders and their prevalence in two primary care practices from the
perspective of different coding].
AB - Family practices provide medical care for the majority of health problems. This
already highlights the importance of primary health care with respect to
quantity. A detailed five-year survey of cases in two rural practices gives
insight into everyday practice. During the whole period of this year's prevalence
survey, 24,541 or 32,605 episodes of care were recorded in a mean practice
population of 1500 or 1700 persons, respectively. The frequency rates of more
than 500 different health problems show a typical Pareto distribution. This
distribution of the cases characterizes the subject of general practice/family
medicine and essentially determines handling illness in practice. Lack of a
common technical language, with regard to the classification of health disorders,
becomes evident when comparing the practices. An issue whose impact on medical
care, education and research should be further investigated.
PMID- 28493141
TI - Therapeutic strategies in adrenoleukodystrophy.
AB - Adrenoleukodystrophy (ALD) is an X-linked hereditary disorder due to mutations of
the ABCD1 gene, which encodes a peroxisomal transport protein necessary for very
long-chain fatty acid degradation (VLCFA). Toxic accumulation thereof is
associated with a proinflammatory state and eventual cell death in multiple
tissues. ALD may manifest either as a fatal, rapidly progressive demyelinating
disease in boys and adult men, or as a slowly progressive adult-onset long-tract
myelopathy along with peripheral neuropathy. Our understanding of manifold
mechanisms implicated in the disease pathology is currently incomplete, as
neither genotype-phenotype correlation nor the trigger for cerebral disease has
been described. Therapy objectives are therefore broadly aimed at correcting
either the gene mutation or downstream molecular effects, such as oxidative
stress. Advancements in disease detection, including the newly implemented
newborn screening in the US and imaging modalities, allow for more timely
intervention in the form of hematopoietic stem cell transplantation (HSCT), which
may only be performed in early cerebral disease states.
PMID- 28493142
TI - Sampling strategy and climatic implication of tree-ring cellulose oxygen isotopes
of Hippophae tibetana and Abies georgei on the southeastern Tibetan Plateau.
AB - The tree-ring cellulose oxygen isotopes (delta18O) for four trees of Hippophae
tibetana and four trees of Abies georgei growing in different locations around
the terminal moraine in Xincuo from 1951 to 2010 were measured to explore its
potential for reconstructing climatic variations in the southeastern Tibetan
Plateau. The mean and standard deviation of tree-ring delta18O at different
heights do not have significant differences, and there are no significant
differences in the mean and standard deviation of tree-ring delta18O between
trees near the brook and trees at the top of moraine, indicating that we can
collect samples for tree-ring delta18O analysis regardless of sampling heights
and that the micro-environment does not affect tree-ring delta18O significantly.
The mean inter-series correlations of cellulose delta18O for A. georgei/H.
tibetana are 0.84/0.93, and the correlation between delta18O for A. georgei and
H. tibetana is 0.92. The good coherence between inter-tree and inter-species
cellulose delta18O demonstrates the possibility of using different species to
develop a long chronology. Correlation analysis between tree-ring delta18O and
climate parameters revealed that delta18O for A. georgei/H. tibetana had negative
correlations (r = -0.62/r = -0.69) with relative humidity in July-August, and
spatial correlation revealed that delta18O for A. georgei/H. tibetana reflected
the regional Standardized Precipitation Evapotranspiration Index (29 degrees -32
degrees N, 88 degrees -98 degrees E). In addition, tree-ring delta18O in Xincuo
has a significant correlation with tree-ring delta18O in Bhutan. The results
indicate that cellulose delta18O for A. georgei and H. tibetana in Xincuo is a
good proxy for the regional hydroclimate.
PMID- 28493143
TI - Differences in the importance of weather and weather-based decisions among
campers in Ontario parks (Canada).
AB - Parks and protected areas represent an important resource for tourism in Canada,
in which camping is a common recreational activity. The important relationship
between weather and climate with recreation and tourism has been widely
acknowledged within the academic literature. Howbeit, the need for activity
specific assessments has been identified as an on-going need for future research
in the field of tourism climatology. Furthermore, very little is known about the
interrelationships between personal characteristics and socio-demographics with
weather preferences and behavioural thresholds. This study uses a stated climate
preferences approach (survey responses) to explore differences in the importance
of weather and related weather-based decisions among summer campers in Ontario
parks. Statistically significant differences were found among campers for each of
the four dependent variables tested in this study. Physically active campers
placed greater importance on weather but were still more tolerant of adverse
weather conditions. Older campers placed greater importance on weather. Campers
travelling shorter distances placed greater importance on weather and were more
likely to leave the park early due to adverse weather. Campers staying for longer
periods of time were less likely to leave early due to weather and were willing
to endure longer durations of adverse weather conditions. Beginner campers placed
greater importance on weather, were more likely to leave early due to weather and
recorded lower temporal weather thresholds. The results of this study contribute
to the study of tourism climatology by furthering understanding of how personal
characteristics such as gender, age, activity selection, trip duration, distance
travelled, travel experience and life cycles affect weather preferences and
decisions, focusing this time on recreational camping in a park tourism context.
PMID- 28493144
TI - Differentiated seasonal vegetation cover dynamics of degraded grasslands in Inner
Mongolia recorded by continuous photography technique.
AB - Influence of climate change on the grassland phenology has attracted more and
more attentions of ecologists. Although dozens of studies have been conducted,
there have been few records examining the phenology differences of grasslands
with different plant species compositions. Using continuous photography and image
processing methods, this study examined seasonal vegetation cover dynamics of
grasslands along a degradation gradient to clarify the influence of vegetation
composition on the dynamics of vegetation cover during growing season. Our
results revealed that phenological patterns of grasslands differentiated with
their degradation status. Abandoned farmland (AF) and severely degraded grassland
(SD) with most annuals and least climax species had the earliest start of growing
season, while AF and extremely degraded grassland (ED) dominated by grasses had
the earliest end of growing season. The start and end of growing season were
strongly related to the relative cover of climax species and grasses. The results
presented in this study support the possibility of using digital photography to
capture the role of plant species composition on vegetation phenology in
grasslands.
PMID- 28493145
TI - Influence of the recipient body mass index on the outcomes after kidney
transplantation.
AB - PURPOSE: The relationship between the body mass index (BMI) of kidney transplant
recipients and outcomes after kidney transplantation (KT) is not fully understood
and remains controversial. We studied the influence of BMI on clinically relevant
outcomes in kidney transplant recipients. METHODS: In this retrospective single
centre study, all patients who underwent kidney transplantation at our
institution between January 2007 and December 2012 were included. Demographic
data and BMI were correlated with the clinical course of the disease, rejection
rates, delayed graft function rates, and graft and patient survival. RESULTS:
During the study period, 384 single KTs (130 women and 254 men) were performed.
Seventeen percent of the transplants were transplanted within the Eurotransplant
Senior Programme (ESP). Most of the transplants were performed using organs that
were obtained from donors after brain death (DBD), and living donor kidney
transplants were performed in 22.4% of all transplants. The median BMI of the
recipients was 25.9 kg/m2. Additionally, 13.5% of the recipients had a BMI of 30
34.9 kg/m2 and 3.9% had a BMI >35 kg/m2. A BMI >30 kg/m2 was significantly
associated with primary non-function of the kidney (p = 0.047), delayed graft
function (p = 0.008), and a higher rate of loss of graft function (p = 0.015).
The glomerular filtration rate 12 months after KT was significantly lower in
recipients with a BMI >30 kg/m2. Multivariate analysis revealed that recipient
BMI, among other factors, was an independent risk factor for delayed graft
function and graft survival. Patients with a BMI >30 kg/m2 had an almost four
times higher risk for surgical site infection than did recipients with a lower
BMI. CONCLUSIONS: Increased BMI at kidney transplantation is a predictor of
adverse outcomes, including delayed graft function. These findings demonstrate
the importance of the careful selection of patients and pre-transplant weight
reduction, although the role of weight reduction for improving graft function is
not clear.
PMID- 28493146
TI - Laparoscopic proximal gastrectomy with oblique jejunogastrostomy.
AB - BACKGROUND: Proximal early gastric cancer is a good indication for totally
laparoscopic proximal gastrectomy (TLPG) with double-tract reconstruction (DTR).
However, when most of the dietary intake passes through the escape route of the
jejunum, the functional benefits of proximal gastrectomy might be similar to
those after total gastrectomy. Our DTR procedure was improved for easy passage
through the remnant stomach. The purposes of this study were to present a novel
technique for intracorporeal DTR using linear staplers after TLPG and to
investigate surgical outcomes. METHODS: DTR was performed using linear staplers
only. A side-to-side jejunogastrostomy with twisting of both the remnant stomach
and the anal jejunum was performed for the purpose of passing meals through the
remnant stomach (an oblique jejunogastrostomy technique). The ten patients who
underwent TLPG with DTR from January 2011 to August 2016 in Hokkaido University
Hospital were retrospectively reviewed. Their clinicopathological characteristics
and surgical and postoperative outcomes were collected and analyzed. RESULTS: The
median duration of operation was 285 (range 146-440) min. No patients required
blood transfusions. The number of dissected lymph nodes was 32 (range 22-56).
There were no intraoperative complications, and no cases were converted to open
surgery. All the patients were pT1N0M0 stage IA. No anastomotic leakage or
complications were detected. Postoperative gastrography after reconstruction
showed that contrast medium flowed mainly to the remnant stomach. The average
percentage body weight loss was 14.0 +/- 7.1% at 10 months. The average
percentage decrease in serum hemoglobin was 5.4 +/- 10.4% at 12 months.
CONCLUSIONS: This novel technique for intracorporeal DTR provided a considerable
advantage by the passage of dietary intake to the remnant stomach after LPG.
PMID- 28493147
TI - Modified ALPPS procedures: more safety through less invasive surgery.
AB - PURPOSE: Although associating liver partition and portal vein ligation for staged
hepatectomy (ALPPS) has been advocated for treating advanced liver tumors,
increased morbidity and mortality remain serious problems. Many modified
procedures have been devised to improve patient safety, but some confusion
persists as to benefits and risks. METHODS: Modifications to ALPPS as originally
reported were reviewed to clarify their contributions to safety and their
clinical relevance. RESULTS: A variety of modifications are explained and
considered. Modifications mainly aim to reduce adhesions, prevent tumor spread,
avoid devascularization during liver splitting, and reduce surgical severity.
Such changes aiming to increase safety and reduce invasiveness are needed to
avoid high morbidity and mortality rates with this innovative procedure. However,
these modified procedures still require more meaningful statistical comparisons
of outcome. CONCLUSIONS: Prospective controlled studies are needed to confirm
which modified procedures should be adopted in a standardized manner as an
alternative to the original ALPPS. Further, we need to further explore mechanisms
of liver regeneration, functional recovery, histopathologic changes of
hepatocytes, and blood distribution during ALPPS simultaneously to developing and
evaluating modifications of the procedure.
PMID- 28493149
TI - Fitting growth curve models in the Bayesian framework.
AB - Growth curve modeling is a popular methodological tool due to its flexibility in
simultaneously analyzing both within-person effects (e.g., assessing change over
time for one person) and between-person effects (e.g., comparing differences in
the change trajectories across people). This paper is a practical exposure to
fitting growth curve models in the hierarchical Bayesian framework. First the
mathematical formulation of growth curve models is provided. Then we give step-by
step guidelines on how to fit these models in the hierarchical Bayesian framework
with corresponding computer scripts (JAGS and R). To illustrate the Bayesian GCM
approach, we analyze a data set from a longitudinal study of marital relationship
quality. We provide our computer code and example data set so that the reader can
have hands-on experience fitting the growth curve model.
PMID- 28493148
TI - Diversity of bacteria and archaea from two shallow marine hydrothermal vents from
Vulcano Island.
AB - To obtain new insights into community compositions of hyperthermophilic
microorganisms, defined as having optimal growth temperatures of 80 degrees C
and above, sediment and water samples were taken from two shallow marine
hydrothermal vents (I and II) with temperatures of 100 degrees C at Vulcano
Island, Italy. A combinatorial approach of denaturant gradient gel
electrophoresis (DGGE) and metagenomic sequencing was used for microbial
community analyses of the samples. In addition, enrichment cultures, growing
anaerobically on selected polysaccharides such as starch and cellulose, were also
analyzed by the combinatorial approach. Our results showed a high abundance of
hyperthermophilic archaea, especially in sample II, and a comparable diverse
archaeal community composition in both samples. In particular, the strains of the
hyperthermophilic anaerobic genera Staphylothermus and Thermococcus, and strains
of the aerobic hyperthermophilic genus Aeropyrum, were abundant. Regarding the
bacterial community, epsilon-Proteobacteria, especially the genera Sulfurimonas
and Sulfurovum, were highly abundant. The microbial diversity of the enrichment
cultures changed significantly by showing a high dominance of archaea,
particularly the genera Thermococcus and Palaeococcus, depending on the carbon
source and the selected temperature.
PMID- 28493150
TI - Assessing liver proteins and enzymes of medical workers exposed to ionizing
radiation (IR).
AB - The cross-sectional study was conducted to examine hepatic function via liver
enzymes/proteins assessments, along with the estimation of an inflammatory
response from C-reactive protein (CRP)-which is a liver-synthesized protein. The
liver function tests with aspartate aminotransferase (AST), alanine
aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin (BBN), and CRP
test were conducted for radiation-exposed workers-REW (n = 32) and radiation
unexposed workers-RUW (n = 21). The annual average effective doses (AAED) were
measured from thermoluminescent dosimeter. A t test and bivariate correlation
analyses were applied. Only one worker had a high AST value (50 U/L), one worker
had a negligible high ALT value (43 U/L) and only one worker had a negligible
high bilirubin value (1.3 g/dL). There were normal levels of CRP (up to 6 mg/L)
in all individuals. There existed a nonsignificant difference (p < 0.050) between
the mean values of liver enzymes and proteins in all exposed and unexposed
workers. Nonsignificant weak correlations are reported in liver enzymes/proteins
parameters: AST, ALT, ALP, BBN, CRP with the AAED range (whole-body: 0.91-3.39
mSv) during 2011-2015. The normal values of liver enzymes/proteins' (AST, ALT,
ALP, BBN, CRP) values may ensure a good hepatic health of radiation-exposed
medical workers with AAED range mentioned. We found that low ionizing radiation
doses did not alter the liver function test parameters and did not affect the
concentration of an inflammatory response protein, i.e., CRP.
PMID- 28493151
TI - Avoidant coping moderates the relationship between stress and depressive
emotional eating in adolescents.
AB - BACKGROUND: Studies with adults support an association between emotional eating
and avoidant and emotion-focused coping styles. While an avoidant coping style
has been identified as a risk-factor for eating disorders in adolescents, no
studies to date have specifically examined the relationship between coping styles
and emotional eating in this population. The purpose of the present study was to
assess whether coping styles moderate the relationship between perceived stress
and emotional eating in adolescents. METHOD: Two hundred and seventy-seven middle
school students (mean age = 13.26 years; SD = 0.49) completed the Emotional
Eating Scale for Children and Adolescents, the Perceived Stress Scale, the
Children's Coping Strategies Checklist, and a brief demographic survey. Four
separate multiple linear regression analyses were conducted to determine the
interactive effects of perceived stress and coping styles on emotional eating.
RESULTS: The interaction between perceived stress and an avoidant coping style
accounted for a significant amount of variance in the Emotional Eating Depression
subscale score (EES-C-DEP); at higher levels of perceived stress, an avoidant
coping style increased an adolescent's propensity for depressive emotional
eating. CONCLUSIONS: The present findings provide preliminary support for
targeting an avoidant coping style in preventative interventions, particularly
for youth that have the propensity to overeat in response to feelings of
depression.
PMID- 28493152
TI - Inhibition of miR-274-3p increases BmCPV replication by regulating the expression
of BmCPV NS5 gene in Bombyx mori.
AB - Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) is one of the major pathogens
that pose a big challenge to the sericulture industry. Growing evidences have
shown that microRNAs play key roles in the regulations of host-pathogen
interactions in insects. MicroRNAs have been found in silkworms, whether and how
they affect the silkworm-BmCPV interactions are still unknown. Here we
investigate the effect of miR-274-3p on the BmCPV replication in the BmCPV
infected silkworm larvae. In our study, BmCPV Nonstructural protein 5 (NS5) was
identified to be the target of miR-274-3p based on bioinformatics analysis and
luciferase reporter assay. The abundance of NS5 was significantly increased in
the presence of miR-274-3p inhibitor based on the qRT-PCR and Western blotting
results. Further, qRT-PCR results revealed that the expression of polyhedrin gene
of BmCPV in the larvae after applying miR-274-3p inhibitor was significantly
increased comparing with that of larvae with negative control. Our results
suggest that inhibition of miR-274-3p could facilitate BmCPV replication by up
regulating BmCPV NS5 gene expression and are insightful for further exploring the
interactions between silkworm and BmCPV.
PMID- 28493153
TI - A Bird's Eye View.
PMID- 28493154
TI - [Transcutaneous osseointegration (part 2)].
PMID- 28493155
TI - ?
PMID- 28493156
TI - Mini-review: high rate algal ponds, flexible systems for sustainable wastewater
treatment.
AB - Over the last 20 years, there has been a growing requirement by governments
around the world for organisations to adopt more sustainable practices.
Wastewater treatment is no exception, with many currently used systems requiring
large capital investment, land area and power consumption. High rate algal ponds
offer a sustainable, efficient and lower cost option to the systems currently in
use. They are shallow, mixed lagoon based systems, which aim to maximise
wastewater treatment by creating optimal conditions for algal growth and oxygen
production-the key processes which remove nitrogen and organic waste in HRAP
systems. This design means they can treat wastewater to an acceptable quality
within a fifth of time of other lagoon systems while using 50% less surface area.
This smaller land requirement decreases both the construction costs and
evaporative water losses, making larger volumes of treated water available for
beneficial reuse. They are ideal for rural, peri-urban and remote communities as
they require minimum power and little on-site management. This review will
address the history of and current trends in high rate algal pond development and
application; a comparison of their performance with other systems when treating
various wastewaters; and discuss their potential for production of added-value
products. Finally, the review will consider areas requiring further research.
PMID- 28493157
TI - Determination of the biofilm production capacities and characteristics of members
belonging to Bacillaceae family.
AB - The biofilm characteristics of many endospore-forming bacilli, especially the
thermophiles are still unclear. In this study, a detailed identification and
description of biofilm production characteristics of totally 145 isolates and
reference strains belonging to Bacillaceae family, displaying thermophilic (n =
115), facultative thermophilic (n = 24) and mesophilic (n = 6) growth from genera
Anoxybacillus, Geobacillus, Thermolongibacillus, Aeribacillus, Brevibacillus,
Paenibacillus and Bacillus were presented. The incubation temperatures were
adjusted to 37, 45 and 55-65 degrees C for mesophiles, facultative thermophiles,
and thermophiles, respectively. The bacilli were evaluated based on their colony
morphotypes on Congo red (CR) agar, their complex exopolysaccharide production on
calcofluor supplemented tryptic soy agar, and as well as their pellicle formation
at the liquid-air surface in tryptic soy broth cultures. Their biofilm production
capabilities were also tested on abiotic surfaces of both polystyrene and
stainless steel by crystal violet binding assay and viable biofilm cell
enumerations, respectively. As a result, the biofilm production capacities of
Bacillaceae members from genera to species level, the effects of osmolarity,
temperature, incubation time and abiotic surfaces on biofilm formation as well as
the CR morphotypes associated with the biofilm production were able to reveal in
a wide group of bacilli. Besides, general enrichment-inoculation approaches and
methodologies were also offered, which allow and facilitate the screening and
determining the biofilm producing endospore forming bacilli.
PMID- 28493159
TI - [Personalized intensive care in the age of standardization].
PMID- 28493160
TI - ?
PMID- 28493158
TI - Common Variable Immunodeficiency Caused by FANC Mutations.
AB - Common variable immunodeficiency (CVID) is the most common adult-onset primary
antibody deficiency disease due to various causative genes. Several genes, which
are known to be the cause of different diseases, have recently been reported as
the cause of CVID in patients by performing whole exome sequencing (WES)
analysis. Here, we found FANC gene mutations as a cause of adult-onset CVID in
two patients. B cells were absent and CD4+ T cells were skewed toward CD45RO+
memory T cells. T-cell receptor excision circles (TRECs) and signal joint kappa
deleting recombination excision circles (sjKRECs) were undetectable in both
patients. Both patients had no anemia, neutropenia, or thrombocytopenia. Using
WES, we identified compound heterozygous mutations of FANCE in one patient and
homozygous mutation of FANCA in another patient. The impaired function of FANC
protein complex was confirmed by a monoubiquitination assay and by chromosome
fragility test. We then performed several immunological evaluations including
quantitative lymphocyte analysis and TRECs/sjKRECs analysis for 32 individuals
with Fanconi anemia (FA). In total, 22 FA patients (68.8%) were found to have
immunological abnormalities, suggesting that such immunological findings may be
common in FA patients. These data indicate that FANC mutations are involved in
impaired lymphogenesis probably by the accumulation of DNA replication stress,
leading to CVID. It is important to diagnose FA because it drastically changes
clinical management. We propose that FANC mutations can cause isolated
immunodeficiency in addition to bone marrow failure and malignancy.
PMID- 28493162
TI - Single-setting endoscopic retrograde cholangiopancreatography (ERCP) and
cholecystectomy improve the rate of surgical site infection.
AB - INTRODUCTION: Cholecystectomy is a common surgical procedure. The presence of
common bile duct stones complicates treatment, often requiring a second procedure
for stone retrieval. For such patients, endoscopic retrograde
cholangiopancreatography (ERCP) provides adequate therapy, and can be performed
before, after, or at the same time as cholecystectomy. In 2013, duodenoscopes
were implicated by the Centers for Disease Control and Prevention in transmission
of carbapenem-resistant Enterobacteriaceae. In this study, we sought to determine
if the addition of ERCP to cholecystectomy was associated with higher rates of
surgical site infections and microbial resistance. HYPOTHESIS: Adding ERCP to
cholecystectomy increases the SSI rate. METHODS: For this retrospective review,
we used the SSI surveillance database at our tertiary-care academic hospital.
Cholecystectomy cases between 2010 and 2015 were included in the analysis. SSI
was diagnosed using criteria of CDC's National Healthcare Safety Network (NHSN).
We applied a logistic regression model to our data (SAS Studio software, v3.4,
Enterprise Edition). RESULTS: Our 6-year study period included 2201
cholecystectomies. The SSI rate was 4.1 times higher for patients who underwent
open cholecystectomy as compared with laparoscopic cholecystectomy (95% CI 1.61
10.24). When adjusted for wound class and procedure type, the SSI rate was
significantly higher for patients who underwent ERCP within 60 days before
cholecystectomy (P = 0.04; OR 2.2; CI 1.04-4.49). Rates of resistant pathogens
were significantly higher in patients who underwent ERCP in addition to
cholecystectomy (1.1% vs. 0.2%, P = 0.02, Fisher's exact test). CONCLUSIONS: ERCP
performed in the same setting as cholecystectomy carries no increased risk of SSI
and should be the treatment of choice in patients with choledocholithiasis. ERCP
performed separately within 60 days before cholecystectomy doubles the risk of
SSI. Contaminated equipment might play a role, but other factors are likely at
play, and should be taken into account when selecting treatment pathways for
patients with choledocholithiasis.
PMID- 28493161
TI - Primary versus redo paraesophageal hiatal hernia repair: a comparative analysis
of operative and quality of life outcomes.
AB - INTRODUCTION: We compared patient outcomes after initial versus redo
paraesophageal hernia (PEH) repair at two high-volume GI surgery centers.
MATERIALS AND METHODS: Retrospective review analyzed one-year outcomes after
initial versus redo elective laparoscopic PEH repair, including wound/non-wound
related complications and quality of life benefits as measured by four validated
instruments: reflux symptom index, gastroesophageal reflux disease health
related, laryngopharyngeal reflux, and swallowing scales. RESULTS: Three hundred
and seventeen patients (271 initial and 46 redo) underwent laparoscopic PEH
repair. Groups differed with respect to age (64.6 vs. 60.2 years, p = 0.027), but
were comparable in gender (71.2 vs. 67.4% female, p = 0.596), BMI (29.0 vs. 27.6
kg/m2, p = 0.100), and ASA score (2.3 vs. 2.3 p = 0.666). Redo surgery was more
complex with longer mean operative times (112.2 vs. 139.1 min, p < 0.001). Groups
did not statistically differ with respect to 30-day wound (0.7 vs. 2.2%, p =
0.363) and non-wound (6.0 vs. 8.7%, p = 0.511)-related complications. After one
year of follow-up, QOL analysis revealed that initial versus redo groups
significantly benefited from operative intervention. CONCLUSIONS: Although redo
PEH repairs are more complex, patients enjoy equivalent operative outcomes and
quality of life benefits compared to initial surgery lending support to the
significance of surgeon experience and high-volume centers in optimizing
outcomes.
PMID- 28493163
TI - A comparison between totally laparoscopic hydrocelectomy and scrotal incision
hydrocelectomy with laparoscopic high ligation for pediatric cord hydrocele.
AB - BACKGROUND: The purpose of this study is to report clinical characteristics and
to investigate the feasibility and safety of totally laparoscopic hydrocelectomy
(TLH) compared to scrotal incision hydrocelectomy with laparoscopic high ligation
(SIH) for pediatric cord hydrocele (CH). METHODS: From September 2011 to February
2016, 148 patients underwent SIH, and 342 patients underwent TLH for CH. In the
TLH group, a large hydrocele that could not pass through the internal ring was
removed after percutaneous syringe aspiration. Age, laterality of hydrocele,
inguinal comorbidities, operation time, surgical complications, and recurrences
were evaluated. RESULTS: All the patients had spermatic cord cysts and patent
processus vaginalis in proximity to hydrocele (mixed type). The mean age of CH
patients was 34.1 +/- 22.1 months. CHs are more common on the right side (61.0%)
than on the left (35.7%). Bilaterality occurred in 3.3%. Comorbidities such as
hernia (8.6%) and cryptorchidism (1.2%) were observed. There were no
complications except for two cases of wound hematoma in SIH group. There was one
(0.7%) case of recurrence appeared in communicating hydrocele in SIH group. There
were no significant differences in the age, laterality of hydrocele, inguinal
comorbidities, operation time, complications, and recurrences between TLH and SIH
groups. However, TLH for unilateral cord hydrocele had significantly shorter
operation time compared to SIH. The mean operation time in TLH group was 15.6 +/-
5.96 min and there was no conversion to open surgery. CONCLUSIONS: TLH for
pediatric CH is a feasible and safe procedure without additional incisions.
Therefore, TLH can be one of the surgical options for pediatric CH especially in
mixed type.
PMID- 28493164
TI - The model for end-stage liver disease predicts outcomes in patients undergoing
cholecystectomy.
AB - BACKGROUND: The magnitude of risk for patients undergoing cholecystectomy with
high model for end-stage liver disease (MELD) scores is poorly understood.
METHODS: The American College of Surgeons National Surgical Quality Improvement
Program database from 2005 to 2013 was used to study patients undergoing
cholecystectomy. Patients were excluded if they had choledocholithiasis or
preoperative dialysis. Bivariate data analysis was performed and logistic
regression modeling was conducted to calculate risk-adjusted 30-day outcomes.
RESULTS: A total of 63,464 patients were included in the study. Unadjusted
mortality significantly increased as the MELD score increased in the laparoscopic
(MELD = 6-10, 0.2%; 11-15, 1.1%; 16-20, 3.2%; >20, 5.8%) and open groups (MELD =
6-10, 1.5%; 11-15, 3.7%; 16-20, 8.6%; >20, 17.9%) (p-value <0.001 for both).
Unadjusted morbidity also increased with MELD score increases in the laparoscopic
(MELD = 6-10, 3.8%; 11-15, 9.9%; 16-20, 16.3%; >20, 22.8%) and open groups (MELD
= 6-10, 18.7%; 11-15, 28.2%; 16-20, 40.7%; >20, 57.8%) (p-value <0.001 for both).
Patients with ascites and high MELD scores had higher rates of mortality
(laparoscopic, MELD > 20, 33.3%; open, MELD > 20, 48.5%) and morbidity
(laparoscopic, MELD > 20, 66.7%; open, MELD > 20, 75.8%) across all MELD scores.
After adjustment, MELD score acted as a progressive and independent predictor of
morbidity and mortality. CONCLUSIONS: The MELD score is an objective and easy to
calculate scoring system that independently predicts postoperative morbidity and
mortality in patients undergoing cholecystectomy. Patients with ascites have
substantially worse outcomes across all MELD scores. Open cholecystectomy is
associated with significantly more morbidity and mortality than laparoscopic
cholecystectomy across all MELD groups.
PMID- 28493165
TI - Minimally invasive distal pancreatectomy: greatest benefit for the frail.
AB - OBJECTIVE: The benefits of minimally invasive distal pancreatectomy (MIDP) over
open surgery continue to be investigated. Frailty is a known predictor of
postoperative outcome. We hypothesized that the benefit of minimally invasive
distal pancreatectomy is the greatest for the frailest of patients. METHODS: Data
from the pancreas-targeted National Surgical Quality Improvement Program (NSQIP)
database for 2014 were reviewed. A modified frailty index (mFI) with 11
preoperative variables previously validated for use in NSQIP was used to
determine the correlation between frailty and postoperative outcomes, including
Clavien grade IV complications. Patients were classified into non-frail (mFI = 0)
or frail (mIF > 0), in which they were subclassified into mildly frail (mFI 1 or
2) or severely frail (mFI = 3). RESULTS: A total of 1,038 distal pancreatectomies
(DP) were included in the analysis, of which 387 were minimally invasive (MIDP:
laparoscopic: 285, robotic: 102), 558 open DP (ODP), and 93 MIDP converted to
open (MIDPcODP: laparoscopic: 80, robotic: 13). More than 90% of patients had an
mFI of 0 or 1 (mFI 0 = 473 (45.6%), 1 = 466 (44.9%), 2 = 94 (9.1%), and 3 = 5
(0.5%), respectively). Overall, 4.6% of patients experienced Clavien grade IV
complications and 1.1% a mortality. Non-frail patients experienced a similar rate
of grade IV Clavien complications with MIDP vs. ODP vs. MIDPcOP (2.3 vs. 2.3 vs.
4.9%; p = 0.6), whereas frail patients (mFI > 0) had a lower rate of
complications with MIDP (2.4 vs. 8.3 vs. 11.5; p = 0.007). Worsening frailty
correlated with an increase in complications (non-frail: 2.5%; mildly frail:
6.3%; severely frail: 20%; p = 0.005). CONCLUSION: MIDP is associated with a
lower risk of Clavien grade IV complications compared to ODP for frail patients,
especially for benign disease. Thus, minimally invasive approach may mitigate
risk in frail patients.
PMID- 28493166
TI - Psychometric properties of the Fundamentals of Endoscopic Surgery (FES) skills
examination.
AB - BACKGROUND: The Fundamentals of Endoscopic Surgery (FES) manual skills
examination is a simulation-based assessment of five foundational skills in
endoscopic surgery. With the FES skills exam becoming part of the board
certification process in general surgery, continual investigation is needed to
determine the validity with which the exam is supporting inferences and decision
making about examinees, as well as how it might be improved. METHODS: The present
study retrospectively analyzed performance and demographic details for the
initial 344 examinees completing the FES skills exam. RESULTS: The five tasks
showed distinct degrees of difficulty, with Loop Reduction being especially
difficult for examinees. Tasks related to one another positively but moderately,
suggesting that the exam assesses both general and task-specific skills. The
number of lower-endoscopic cases completed by an examinee strongly predicted
performance, while upper endoscopy experience and career level (e.g., resident
vs. fellow vs. practicing) did not. Hand dominance and the type of simulator used
were not found to be related to scores. However, three demographic variables that
related to one another-gender, glove size, and height-were also related to
performance and pass/fail status. CONCLUSIONS: This study's results generally
support the validity argument for the FES skills exam while pointing to
additional investigations to be undertaken as the exam is applied more broadly.
PMID- 28493167
TI - Diagnostic yield of small histological cores obtained with a new EUS-guided fine
needle biopsy system.
AB - BACKGROUND: As endoscopic ultrasound-guided tissue acquisition techniques evolve,
there is increasing interest in obtaining optimal histological samples to improve
diagnostic accuracy. In this study, we aimed to assess the tissue acquisition
success rate and test performance characteristics of a novel endoscopic
ultrasound-guided fine needle biopsy (EUS-FNB) system. METHODS: We performed a
retrospective review of consecutive patients undergoing EUS-guided tissue
sampling of solid lesions using the SharkCore fine needle system in a tertiary
referral facility. At least two passes were submitted for histology and
diagnostic accuracy was evaluated. Comparison standard was based on final
surgical pathology or minimum six-month clinical follow-up. RESULTS: Seventy-nine
patients underwent 85 EUS-FNB procedures. Of the 85 histology specimens, 78
(91.7%) were adequate for diagnostic examination (includes six
atypical/suspicious for adenocarcinoma). The sensitivity, specificity, and
accuracy for diagnosis of malignancy with FNB were 87.1, 100, and 90.6%,
respectively. Cytology was simultaneously sent in 43 cases with the same needle
in addition to histology. Out of the 14 cases that were atypical/suspicious for
adenocarcinoma or non-diagnostic on cytology, 11 cases (78.6%) achieved definite
diagnoses on histology. The overall sensitivity, specificity, and accuracy for
diagnosis of malignancy combining histology and cytology were 90.3, 100, and
92.9%, respectively. No complications were reported after the procedures.
CONCLUSION: In this initial experience with a new EUS-guided FNB system,
obtaining small cores to submit for histological analysis was safe, technically
feasible, and highly accurate. Most of the histological cores obtained via FNB
yielded a definite diagnosis including in cases with equivocal cytomorphology.
Further study is required to confirm these findings.
PMID- 28493168
TI - Comparative statistical component analysis of transgenic, cyanophycin-producing
potatoes in greenhouse and field trials.
AB - Potatoes are a promising system for industrial production of the biopolymer
cyanophycin as a second compound in addition to starch. To assess the efficiency
in the field, we analysed the stability of the system, specifically its
sensitivity to environmental factors. Field and greenhouse trials with transgenic
potatoes (two independent events) were carried out for three years. The influence
of environmental factors was measured and target compounds in the transgenic
plants (cyanophycin, amino acids) were analysed for differences to control
plants. Furthermore, non-target parameters (starch content, number, weight and
size of tubers) were analysed for equivalence with control plants. The huge
amount of data received was handled using modern statistical approaches to model
the correlation between influencing environmental factors (year of cultivation,
nitrogen fertilization, origin of plants, greenhouse or field cultivation) and
key components (starch, amino acids, cyanophycin) and agronomic characteristics.
General linear models were used for modelling, and standard effect sizes were
applied to compare conventional and genetically modified plants. Altogether, the
field trials prove that significant cyanophycin production is possible without
reduction of starch content. Non-target compound composition seems to be
equivalent under varying environmental conditions. Additionally, a quick test to
measure cyanophycin content gives similar results compared to the extensive
enzymatic test. This work facilitates the commercial cultivation of cyanophycin
potatoes.
PMID- 28493170
TI - Eluxadoline: A Review in Diarrhoea-Predominant Irritable Bowel Syndrome.
AB - Eluxadoline (Truberzi(r)) is an orally administered, minimally absorbed agent
that acts locally in the gastrointestinal tract as a mixed u-opioid receptor
agonist and delta-opioid receptor antagonist. The randomized, double-blind,
placebo-controlled, multinational, phase 3 IBS-3001 and IBS-3002 trials examined
the efficacy of eluxadoline in patients with diarrhoea-predominant irritable
bowel syndrome (IBS-D). The composite response rate (i.e. the proportion of
patients with improvement in both worst abdominal pain and stool consistency on
>=50% of days; primary endpoint), was significantly higher in patients receiving
eluxadoline 100 mg twice daily than in those receiving placebo after 12 and 26
weeks' therapy. Other abdominal and bowel symptoms (e.g. bloating, urgency,
frequency of bowel movement) and health-related quality of life scores were also
improved with eluxadoline. Eluxadoline was generally well tolerated in patients
with IBS-D. Constipation was the most commonly occurring adverse event, although
no serious constipation events were reported. Pancreatitis and adverse events
consistent with sphincter of Oddi spasm were uncommon. In conclusion, eluxadoline
is a new option to consider in the treatment of adult patients with IBS-D.
PMID- 28493169
TI - Empathy for Distress in Humans and Rodents.
AB - Empathy is traditionally thought to be a unique ability of humans to feel,
understand, and share the emotional state of others. However, the notion has been
greatly challenged by the emerging discoveries of empathy for pain or distress in
rodents. Because empathy is believed to be fundamental to the formation of
prosocial, altruistic, and even moral behaviors in social animals and humans,
studies associated with decoding the neural circuits and unraveling the
underlying molecular and neural mechanisms of empathy for pain or distress in
rodents would be very important and encouraging. In this review, the author set
out to outline and update the concept of empathy from the evolutionary point of
view, and introduce up-to-date advances in the study of empathy and its neural
correlates in both humans and rodents. Finally, the author highlights the
perspectives and challenges for the further use of rodent models in the study of
empathy for pain or distress.
PMID- 28493171
TI - Immunotherapy in Urothelial Cancer: Recent Results and Future Perspectives.
AB - Cytotoxic chemotherapy has been the only systemic treatment of locally advanced
and metastatic urothelial carcinoma for decades. Long-term survival remains
stagnant around 12-14 months for patients with advanced disease who have
progressed on or recurred after receiving first-line platinum-based chemotherapy.
Improving clinical outcomes for patients with urothelial carcinoma in all disease
settings requires the development of novel treatments, especially for patients
who failed on first-line chemotherapy. Since the discovery of intravesical
Bacillus-Calmette Guerin (BCG) in the 1970s for non-muscle invasive disease,
there have not been any major breakthrough drugs that exploit the immune
sensitivity of bladder cancer until recently. Immune-checkpoint inhibitors
targeting the programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) and
cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) pathways have shown
significant anti-tumor activity, tolerable safety profiles and durable, long-term
responses in clinical trials. Atezolizumab, avelumab, durvalumab, nivolumab and
pembrolizumab are promising PD-1/PD-L1 blockade drugs under investigation that
will redefine the standard of care for bladder cancer. CTLA-4 inhibitors are also
under investigation in this setting. Atezolizumab, approved in May 2016, and
nivolumab, approved in February 2017, are the first Food and Drug Administration
(FDA)-approved immune-checkpoint inhibitors in bladder cancer for platinum
pretreated patients based on phase II data. On March 16, 2017, results from the
phase III trial KEYNOTE-045 demonstrated that survival was significantly longer
in patients treated with pembrolizumab when compared with the standard second
line chemotherapy. Research into biomarkers such as PD-L1 expression, messenger
RNA subtype, mutational and neoantigen load and gene signature expression will be
crucial to determining why some patients respond to immunotherapy and others do
not. This review article describes the advances in immunotherapy since the
development of BCG, presents results from clinical trials investigating immune
checkpoint inhibitors and discusses biomarkers and prognostic factors associated
with response to these new drugs.
PMID- 28493172
TI - Tenofovir Alafenamide: A Review in Chronic Hepatitis B.
AB - Tenofovir alafenamide (AF) [Vemlidy(r)], an oral prodrug of tenofovir, was
developed to optimize the antiviral potency and clinical safety of the active
moiety tenofovir diphosphate (selective reverse transcriptase nucleotide
inhibitor). In two identically designed, ongoing, multinational trials in
treatment-naive and -experienced adult patients with hepatitis B e antigen
(HBeAg)-positive or -negative chronic hepatitis B virus (HBV) infection, once
daily tenofovir AF 25 mg provided effective and sustained viral suppression (120
week analysis), and was generally well tolerated. In the primary 48-week
analysis, tenofovir AF was noninferior to once-daily tenofovir disoproxil
fumarate (DF) 300 mg in terms of the proportion of patients achieving viral
suppression (HBV DNA <29 IU/mL) and was associated with significantly higher
alanine aminotransferase (ALT) normalization rates than tenofovir DF based on
AASLD criteria (but not central laboratory criteria). In pooled analyses and/or
individual trials, ALT normalization rates by AASLD and central laboratory
criteria were significantly higher in tenofovir AF than tenofovir DF recipients
at most assessed timepoints up to 96 weeks. Given the bone and renal safety
concerns associated with long-term tenofovir DF treatment, the more favourable
pharmacological profile of tenofovir AF permits a marked reduction in the dosage
of this tenofovir prodrug and thereby reduces systemic exposure to tenofovir,
potentially improving the bone and renal safety of tenofovir AF versus tenofovir
DF. Long-term clinical experience will more definitively establish the relative
bone and renal safety of these tenofovir prodrugs. With its potential for an
improved safety profile, tenofovir AF is an important emerging first-line option
for the treatment of chronic HBV infection in adults and adolescents (aged >=12
years and with a bodyweight of >=35 kg).
PMID- 28493173
TI - Idiopathic inflammatory myopathy and the risk of venous thromboembolism: a meta
analysis.
AB - This study aimed at analyzing published data on the association between
idiopathic inflammatory myopathy and venous thromboembolism (VTE). We examined
studies on VTE risk in patients with polymyositis (PM) and/or dermatomyositis
(DM), in the MEDLINE, EMBASE, and Cochrane databases and via manual searches. We
performed a meta-analysis on the relative risks (RRs) of VTE, pulmonary embolism
(PE), and deep vein thrombosis (DVT) in these patients. Five studies, including
8858 patients with PM/DM met the inclusion criteria. Meta-analysis revealed a
significant association between PM/DM and VTE risk (RR = 4.364, 95% CI 2.128
8.949, p = 5.8 * 10-5). A significant association was found between PE risk and
PM/DM (RR = 3.504, 95% CI 2.856-4.300, p < 1.0 * 10-8). Meta-analysis also
indicated a significant association between DVT risk and PM/DM (RR = 7.481, 95%
CI 3.355-16.68, p = 8.7 * 10-7). This meta-analysis demonstrated that both types
of PM/DM are associated with an elevated risk of VTE, PE, and DVT, suggesting
that patients with PM/DM should be carefully monitored for development of these
conditions.
PMID- 28493174
TI - Genomics, transcriptomics and proteomics to elucidate the pathogenesis of
rheumatoid arthritis.
AB - Rheumatoid arthritis is an autoimmune disease that affects several organs and
tissues, predominantly the synovial joints. The pathogenesis of this disease is
not completely understood, which maybe involved in the genomic variations, gene
expression, protein translation and post-translational modifications. These
system variations in genomics, transcriptomics and proteomics are dynamic in
nature and their crosstalk is overwhelmingly complex, thus analyzing them
separately may not be very informative. However, various '-omics' techniques
developed in recent years have opened up new possibilities for clarifying disease
pathways and thereby facilitating early diagnosis and specific therapies. This
review examines how recent advances in the fields of genomics, transcriptomics
and proteomics have contributed to our understanding of rheumatoid arthritis.
PMID- 28493175
TI - Treatment for lupus nephritis: an overview of systematic reviews and meta
analyses.
AB - The aim is to systematically review the treatment for lupus nephritis (LN) by
performing an overview of systematic reviews and meta-analyses. Electronic
databases of OVID MEDLINE, OVID EMBASE, and Cochrane Library were searched to
identify published systematic reviews and meta-analyses investigating treatments
for LN up to 13 July 2016. A measurement tool to assess systematic reviews
(AMSTAR) was used to assess the quality of included studies. Totally, 24 studies
were included. Of the eligible studies, 3 studies were rated as poor quality, 11
as moderate, and 10 as good. In LN induction therapy, comparing to
cyclophosphamide, tacrolimus had higher complete remission rate, response rate,
and anti-dsDNA negative conversion rate and led to lower risks of
gastrointestinal symptoms and amenorrhea, and mycophenolate mofetil (MMF) was
associated with higher response rate and less adverse events of leucopenia,
alopecia, and ovarian failure. However, there was no difference in the efficacy
and adverse events between tacrolimus and MMF. In LN maintenance therapy, the
relapse rate and leucopenia rate were lower in MMF group than in azathioprine
group, but there were no differences of end-stage kidney disease rate and
mortality rate between the two groups. For LN induction therapy, both Tacrolimus
and MMF are more effective and safer than cyclophosphamide, while there are no
differences of efficacy or safety between the two treatments. For LN maintenance
therapy, MMF seems to have less adverse events and lower relapse rate than
azathioprine.
PMID- 28493176
TI - The Effectiveness of Psychosocial Interventions Delivered by Teachers in Schools:
A Systematic Review and Meta-Analysis.
AB - The growing mental health needs of students within schools have resulted in
teachers increasing their involvement in the delivery of school-based,
psychosocial interventions. Current research reports mixed findings concerning
the effectiveness of psychosocial interventions delivered by teachers for mental
health outcomes. This article presents a systematic review and meta-analysis that
examined the effectiveness of school-based psychosocial interventions delivered
by teachers on internalizing and externalizing outcomes and the moderating
factors that influence treatment effects on these outcomes. Nine electronic
databases, major journals, and gray literature (e.g., websites, conference
abstract) were searched and field experts were contacted to locate additional
studies. Twenty-four studies that met the study inclusion criteria were coded
into internalizing or externalizing outcomes and further analyzed using robust
variance estimation in meta-regression. Both publication and risk of bias of
studies were further assessed. The results showed statistically significant
reductions in students' internalizing outcomes (d = .133, 95% CI [.002, .263])
and no statistical significant effect for externalizing outcomes (d = .15, 95% CI
[-.037, .066]). Moderator analysis with meta-regression revealed that gender
(%male, b = -.017, p < .05), race (% Caucasian, b = .002, p < .05), and the tier
of intervention (b = .299, p = .06) affected intervention effectiveness. This
study builds on existing literature that shows that teacher-delivered Tier 1
interventions are effective interventions but also adds to this literature by
showing that interventions are more effective with internalizing outcomes than on
the externalizing outcomes. Moderator analysis also revealed treatments were more
effective with female students for internalizing outcomes and more effective with
Caucasian students for externalizing outcomes.
PMID- 28493177
TI - What is Single-Payer Health Care? A Review of Definitions and Proposals in the
U.S.
AB - BACKGROUND: Single-payer systems have been proposed as a health care reform
alternative in the United States. However, there is no consensus on the
definition of single-payer. Most definitions characterize single-payer as one
entity that collects funds and pays for health care on behalf on an entire
population. Increased flexibility for state health care reform may provide
opportunities for state-based single-payer systems to be considered. OBJECTIVE:
To explore the concept of single-payer and to describe the contents of single
payer health care proposals. DESIGN: We compared single-payer definitions and
proposals. We coded the proposal text for provisions that would change how the
health care system functions and could impact health care access, quality, and
cost. MAIN MEASURES: The share of proposals that include changes to the
financing, pooling, purchasing, and delivery of health care; and possible impact
on access, quality, and costs. KEY RESULTS: We identified 25 proposals for
national or state single-payer plans from journal and legislative databases. The
proposals typically call for wide-ranging reform; nearly all include changes
across the financing, pooling, purchasing, and delivery of health care services.
Many provisions aiming to improve access, quality, and cost containment are also
included, but the proposals vary in how they plan to achieve these improvements.
Common provisions are related to comprehensive benefits, patient choice of
providers, little or no cost sharing, the role of private insurance, provider
guidelines and standards, periodic reviews of the benefits package, electronic
medical records and billing, prescription drug formulary, global budgets,
administrative cost thresholds, payment reform and studies, and the authority to
implement cost-containment strategies. CONCLUSIONS: Single-payer systems are
heterogeneous. Acknowledgment of what is considered as single-payer and the
characteristics that are variable is important for nuanced policy discussions on
specific reform proposals.
PMID- 28493178
TI - Language Barriers, Informed Consent, and Effective Caregiving.
PMID- 28493179
TI - Where to position osteotomies in genioglossal advancement surgery based on
locations of the mental foramen, canine, lateral incisor, central incisor, and
genial tubercle.
AB - PURPOSE: The study aimed to provide precise measurements of anterior mandibular
structural anatomy and to explore potential osteotomies for genioglossal
advancement. METHODS: Cone beam computed tomography was used to analyze 33
randomly selected patients undergoing surgery for obstructive sleep apnea (OSA)
between 2014 and 2016 at an academic surgical hospital. The locations of relevant
mandibular structures were measured and statistical modeling was performed.
RESULTS: Mean horizontal distances from midline to the mental foramina and the
roots of the canine, lateral incisor, and central incisor were 22.11 +/- 1.92,
13.56 +/- 3.01, 6.19 +/- 1.58, and 2.04 +/- 0.87 mm, respectively. Mean vertical
distances from the inferior border of the mandible were 15.15 +/- 1.77, 17.11 +/-
3.28, 20.48 +/- 3.10, and 21.81 +/- 3.49 mm, respectively. The superior border of
the genial tubercle was 15.63 +/- 2.75 mm, and the inferior border was 6.87 +/-
3.29, from the inferior border of the mandible. The angle of decline of the best
fit line through the important structures was about 18 degrees from the
occlusion plane at the midline. CONCLUSIONS: A straight line estimating the
mental foramen, canine, lateral incisor, and central incisor tooth roots crosses
at a mean of 22.3-22.6 mm above the inferior border of the mandible at the
midline and has an angle of decline of about 18 degrees . Potential osteotomies
made parallel to and below this line result in tradeoffs between maximizing
capture of the genioglossus muscle attachment and risk of dental/neurovascular
injury.
PMID- 28493180
TI - Erratum to: The Molecular Basis of Evolution and Disease: A Cold War Alliance.
PMID- 28493181
TI - Assessment of hydrogen sulfide emission from a sewage treatment plant using
AERMOD.
AB - Air quality modeling plays an important role in prediction of air pollutants in
urban areas. Moreover, it is also an essential component to make crucial
decisions in environmental management. In this study, environmental protection
agency (EPA) regulatory model (AERMOD) was implemented in order to assess the
urban air quality in the city of Muscat, Sultanate of Oman. Dispersion modeling
was employed for the prediction of hydrogen sulfide (H2S) emissions, a
neighborhood claimed issue, from Al-Ansab sewage treatment plant (STP).
Meteorological, elevation data, and H2S survey results were implemented into the
model. From the site survey study, four different H2S emission sources were
identified as sewage tanker connection points, biofilter, old odor control unit
(OCU), and open channels of raw sewage. It was observed that based on maximum 24
h analysis, the ground level concentration outside the STP exceeded the
concentration limit, 40 MUg/m3, recommended by the local regulating agency in
Oman. By applying a sensitivity analysis study, the locations with the highest
predicted H2S levels were identified. The most affected area in the worst-case
scenario was the nearby expressway with 450.9 MUg/m3 of H2S. The highest ground
level concentration of H2S was detected in March, while the lowest was measured
in December. The model also predicted that the impact of odor nuisance is greater
at the summer season than that of other seasons due to the elevated temperatures.
The study revealed an adverse environmental impact from the STPs on urban air
quality, which may pose a threat to the public health.
PMID- 28493182
TI - Modeling seasonal and spatial contamination of surface waters and upper sediments
with trace metal elements across industrialized urban areas of the Seybouse
watershed in North Africa.
AB - Industrialization and urbanization are the main sources of pollutions worldwide
and particularly in developing countries. This study aims the determination of
anthropogenic inputs with trace metals in aquatic ecosystems at the Plain of
Annaba (NE Algeria), which is known as one of the largest industrial areas in
Africa. Samples of surface waters and upper sediments were conducted in six
stations: four in Meboudja wadi and two in Seybouse wadi. Contents of iron,
copper, chromium, nickel, zinc, and manganese were measured by atomic absorption
spectrophotometry, whereas Cd and Pb were determined using electrothermal atomic
absorption spectrometry. Measurements of Hg were carried out using atomic
fluorescence. Spatiotemporal variations of metal concentrations were tested using
generalized linear models (GLM), whereas the influence of water pollution on
sediment contamination was tested with generalized additive models (GAMs). Metal
contents measured in surface water and sediments varied differently from upstream
to downstream of the study wadis and between seasons. The results showed that the
surface water was polluted with high levels of iron, nickel, chromium, lead, and
cadmium. Values of the contamination index revealed that the surface sediments
were contaminated by iron, chromium, lead, and cadmium. The GAMs indicated that
water-phase metal concentrations had no significant effects on trace metal
concentrations in the sediment. This suggests that seasonal metal concentrations
in water phase, which are measured during the study period (2012) and are time
dependent, contribute increasingly and gradually over time-not immediately-to the
accumulation of metals into the sediments. Therefore, the long-term accumulation
of metals in the sediments resulted from the continuous discharges of metals in
the water phase. The anthropogenic impacts are marked by high contaminations of
Meboudja wadi particularly in downstream areas of the steel factory and the
nearby industrial areas. The direct industrial discharges into the water and
atmosphere (iron, lead, cadmium) as well as urban disposals and agricultural
activities are at the origin of these contaminations.
PMID- 28493183
TI - Geochemical characterization of fluoride in water, table salt, active sediment,
rock and soil samples, and its possible relationship with the prevalence of
enamel fluorosis in children in four municipalities of the department of Huila
(Colombia).
AB - Fluoride is an element that affects teeth and bone formation in animals and
humans. Though the use of systemic fluoride is an evidence-based caries
preventive measure, excessive ingestion can impair tooth development, mainly the
mineralization of tooth enamel, leading to a condition known as enamel fluorosis.
In this study, we investigated the geochemical characterization of fluoride in
water, table salt, active sediment, rock and soil samples in four endemic enamel
fluorosis sentinel municipalities of the department of Huila, Colombia (Pitalito,
Altamira, El Agrado and Rivera), and its possible relationship with the
prevalence of enamel fluorosis in children. The concentration of fluoride in
drinking water, table salt, active sediment, rock, and soil was evaluated by
means of an ion selective electrode and the geochemical analyses were performed
using X-ray fluorescence. Geochemical analysis revealed fluoride concentrations
under 15 mg/kg in active sediment, rock and soil samples, not indicative of a
significant delivery to the watersheds studied. The concentration of fluoride in
table salt was found to be under the inferior limit (less than 180 MUg/g)
established by the Colombian regulations. Likewise, exposure doses for fluoride
water intake did not exceed the recommended total dose for all ages from 6
months. Although the evidence does not point out at rocks, soils, fluoride
bearing minerals, fluoridated salt and water, the hypothesis of these elements as
responsible of the current prevalence of enamel fluorosis cannot be discarded
since, aqueducts might have undergone significant changes overtime.
PMID- 28493184
TI - The Moderating Role of Spirituality in the Association between Stress and
Substance Use among Adolescents: Differences by Gender.
AB - Adolescents are exposed to various stressors that may increase the risk for
substance use. Due to the detrimental, and potentially long-lasting, effects
related to substance use, it is necessary to explore more optimal coping
strategies. This study explored the association between substance use and stress
among male and female high school students in relation to spirituality as a
moderator. To examine these relationships, the study used cross-sectional data
collected from 27,874 high school students (Male = 50.7%, Female = 49.3%) across
58 high schools in Maryland that included an ethnically diverse sample (49%
Caucasian, 30% African American) with an average age of 16 years old. Bivariate
results showed differences in substance use, stress, and spirituality between
male and female students. Higher rates of substance use were generally found
among male students compared to female students; rates tended to be higher among
female students for stress and spirituality compared to their male counterparts.
Multilevel analyses indicated a positive association between stress and substance
use among male and female students after adjusting for demographic and school
level factors. Both male and female students who reported turning to spiritual
beliefs when experiencing problems were less likely to use substances. However,
the interaction between stress and spirituality was significant for males only.
These findings suggest that stress may increase the propensity for substance use
and that spirituality might be a viable coping mechanism useful for helping high
school students adapt to stressful circumstances and situations.
PMID- 28493185
TI - Dietary PUFA Increase Apoptosis in Stomach of Patients with Dyspeptic Symptoms
and Infected with H. pylori.
AB - Drug-resistant strains of Helicobacter pylori and poor treatment response are the
main reasons for the failure in eradicating it in patients. Polyunsaturated fatty
acids (PUFA) have an inhibitory effect on bacterial growth. The aim of this study
was to investigate the effect of PUFA in combination with standard triple therapy
on apoptosis in H. pylori infected subjects with dyspeptic symptoms. This study
was a double-blind clinical trial in which 34 H. pylori infected subjects with
dyspeptic symptoms were randomly divided into two groups of 17 patients. The
control group received standard triple therapy (amoxicillin, clarithromycin and
omeprazole) and the experimental group received the standard therapy and PUFA for
two weeks. Gene expression levels of caspase-3, BCL-2 and Bad proteins were
studied with real-time PCR, while protein levels were quantified in frozen
sections and using immunohistochemistry. Compared with the control group, a
significant increase (p < 0.01) was observed in the expression of caspase-3 and
Bad genes and a significant reduction (p < 0.05) in the expression of Bcl-2 gene.
The protein level of active caspase-3 and Bad protein was significantly increased
and the level of Bcl-2 protein was significantly decreased (p < 0.05). The
results of this study show that oral administration of PUFA in combination with
the standard triple therapy increased apoptosis in H. pylori-infected patients
with dyspeptic symptoms. This increase in apoptosis may partly reduce drug
resistance in these patients. Our results suggest inclusion of a dietary PUFA
containing fatty acid supplement may improve treatment of patients that are
refractory to the standard triple therapy.
PMID- 28493186
TI - Analysis of ecotoxic influence of waste from the biomass gasification process.
AB - The purpose of this research was evaluation of the effect of soil contamination
with waste coming from biomass gasification on chosen indicators of its
biological activity, growth and development of spring barley, and change of
physiological parameters of the plant. Chromatographic content and basic
rheological parameters of the substances under research were also analyzed.
Liquid wastes, tar, and mixture of tar and engine oil were introduced to the soil
in the amount of 100 mg kg-1 DM soil. Based on the conducted research, it was
ascertained that the changes in the number and activity of soil microorganisms
were determined by the type of waste and its dose. Individual groups of
microorganisms showed different sensitivity to the presence of pollution;
however, the impact of tar and engine oil mixture was generally more
disadvantageous. Presence of contaminants in the soil limited the growth of roots
and aboveground parts of spring barley, especially when the dose was 10,000 mg kg
1 DM soil. The unfavorable impact of waste on photosynthesis efficiency on
assimilation pigment synthesis and water content in the plant was recorded.
PMID- 28493188
TI - Are renewable energy policies upsetting carbon dioxide emissions? The case of
Latin America countries.
AB - The impact of renewable energy policies in carbon dioxide emissions was analysed
for a panel of ten Latin American countries, for the period from 1991 to 2012.
Panel autoregressive distributed lag methodology was used to decompose the total
effect of renewable energy policies on carbon dioxide emissions in its short- and
long-run components. There is evidence for the presence of cross-sectional
dependence, confirming that Latin American countries share spatial patterns.
Heteroskedasticity, contemporaneous correlation, and first-order autocorrelation
cross-sectional dependence are also present. To cope with these phenomena, the
robust dynamic Driscoll-Kraay estimator, with fixed effects, was used. It was
confirmed that the primary energy consumption per capita, in both the short- and
long-run, contributes to an increase in carbon dioxide emissions, and also that
renewable energy policies in the long-run, and renewable electricity generation
per capita both in the short- and long-run, help to mitigate per capita carbon
dioxide emissions.
PMID- 28493187
TI - The short-term associations of weather and air pollution with emergency ambulance
calls for paroxysmal atrial fibrillation.
AB - A circadian variation in the cardiovascular parameters has been detected. It is
plausible that the influence of the environment varies during different periods
of the day. We investigated the association between daily emergency ambulance
calls (EC) for paroxysmal atrial fibrillation (AF) that occurred during the time
intervals of 8:00-13:59, 14:00-21:59, and 22:00-7:59, and weather conditions and
exposure to CO and PM10. We used Poisson regression to explore the association
between the risk of EC for AF and environmental variables, adjusting for seasonal
variation. Before noon, the risk was associated with an IQR (0.333 mg/m3)
increase in CO at lag 2-6 days above the median (RR = 1.15, P = 0.002); a
protective impact of CO on previous day was observed (RR = 0.91, P = 0.018).
During 14:00-21:59, a negative effect of air temperature below 1.9 degrees C
(lag 2-3 days) was detected (per 10 degrees C decrease: RR = 1.17, P = 0.044).
At night, the elevated risk was associated with wind speed above the median (lag
2-4 days) (per 1-kt increase: RR = 1.07, P = 0.001) and with PM10 at lag 2-5 days
below the median (per IQR (7.31 MUg/m3) increase: RR = 1.21, P = 0.002).
Individuals over 65 years of age were more sensitive to air pollution, especially
at night (CO lag 2-3 days < median, per IQR (0.12 mg/m3) increase: RR = 1.14, P =
0.045; PM10 lag 2-5 days < median, per IQR increase: RR = 1.32, P = 0.001). The
associations of air pollution and other environmental variables with acute events
may be analyzed depending on the time of the event.
PMID- 28493189
TI - The treatment of wastewater containing pharmaceuticals in microcosm constructed
wetlands: the occurrence of integrons (int1-2) and associated resistance genes
(sul1-3, qacEDelta1).
AB - The aim of this study was to analyze the occurrence of sulfonamide resistance
genes (sul1-3) and other genetic elements as antiseptic resistance gene
(qacEDelta1) and class 1 and class 2 integrons (int1-2) in the upper layer of
substrate and in the effluent of microcosm constructed wetlands (CWs) treating
artificial wastewater containing diclofenac and sulfamethoxazole (SMX), which is
a sulfonamide antibiotic. The bacteria in the substrate and in the effluents were
equipped with the sul1-2, int1, and qacEDelta1 resistance determinants, which
were introduced into the CW system during inoculation with activated sludge and
with the soil attached to the rhizosphere of potted seedlings of Phalaris
arundinacea 'Picta' roots (int1). By comparing the occurrence of the resistance
determinants in the upper substrate layer and the effluent, it can be stated that
they neither were lost nor emerged along the flow path. The implications of the
presence of antibiotic resistance genes in the effluent may entail a risk of
antibiotic resistance being spread in the receiving environment. Additionally,
transformation products of SMX were determined. According to the obtained
results, four (potential) SMX transformation products were identified. Two major
metabolites of SMX, 2,3,5-trihydroxy-SMX and 3,5-dihydroxy-SMX, indicated that
SMX may be partly oxidized during the treatment. The remaining two SMX
transformation products (hydroxy-glutathionyl-SMX and glutathionyl-SMX) are
conjugates with glutathione, which suggests the ability of CW bacterial community
to degrade SMX and resist antimicrobial stress.
PMID- 28493190
TI - Preparation of a new Fenton-like catalyst from red mud using molasses wastewater
as partial acidifying agent.
AB - Using molasses wastewater as partial acidifying agent, a new Fenton-like catalyst
(ACRM sm ) was prepared through a simple process of acidification and calcination
using red mud as main material. With molasses wastewater, both the free alkali
and the chemically bonded alkali in red mud were effectively removed under the
action of H2SO4 and molasses wastewater, and the prepared ACRM sm was a near
neutral catalyst. The ACRM sm preparation conditions were as follows: for 3 g of
red mud, 9 mL of 0.7 mol/L H2SO4 plus 2 g of molasses wastewater as the
acidifying agent, calcination temperature 573 K, and calcination time 1 h. Iron
phase of ACRM sm was mainly alpha-Fe2O3 and trace amount of carbon existed in
ACRM sm . The addition of molasses wastewater not only effectively reduced the
consumption of H2SO4 in acidification of red mud but also resulted in the
generation of carbon and significantly improved the distribution of macropore in
prepared ACRM sm . It was found that near-neutral pH of catalyst, generated
carbon, and wide distribution of macropore were the main reasons for the high
catalytic activity of ACRM sm . The generated carbon and wide distribution of
macropore were entirely due to the molasses wastewater added. In degradation of
orange II, ACRM sm retained most of its catalytic stability and activity after
five recycling times, indicating ACRM sm had an excellent long-term stability in
the Fenton-like process. Furthermore, the performance test of settling showed
ACRM sm had an excellent settleability. ACRMsm was a safe and green catalytic
material used in Fenton-like oxidation for wastewater treatment.
PMID- 28493191
TI - Distribution and variation of mercury in frozen soils of a high-altitude
permafrost region on the northeastern margin of the Tibetan Plateau.
AB - The Tibetan Plateau (TP) is home to the largest permafrost bodies at low- and mid
latitudes, yet little is known about the distribution and variation of mercury
(Hg) in frozen soil of the permafrost regions. In this study, extensive soil
sampling campaigns were carried out in 23 soil pits from 12 plots in a high
altitude permafrost region of the Shule River Basin, northeastern TP. Hg
distribution, variation, and their dependences on soil properties were analyzed.
The results have revealed that total Hg (THg) concentrations were low ranging
from 6.3 to 29.1 ng g-1. A near-surface peak of THg concentrations followed by a
continuous decrease were observed on the vertical profiles of most soil pits.
Significant positive relationships among THg concentrations, soil organic carbon
(SOC) contents, and silty fractions were observed, indicating that SOC content
and silty fraction are two dominant factors influencing the spatial distribution
of THg. THg concentrations in soils showed a decreasing trend with altitude,
which was probably attributed to a lower soil potential to Hg accumulation under
the condition of lower SOC contents and silty fractions at high altitudes.
Approximately, 130.6 t Hg in soils (0-60 cm) was estimated and a loss of 64.2% of
Hg from the highly stable and stable permafrost (H-SP) region via permafrost
degradation was expected in the upstream regions of the Shule River Basin,
indicating that the large areas of permafrost regions may become an important
source of global Hg emission as a result of the ongoing widespread permafrost
degradation.
PMID- 28493192
TI - Simulating water and nitrogen loss from an irrigated paddy field under
continuously flooded condition with Hydrus-1D model.
AB - Agricultural non-point source pollution is a major factor in surface water and
groundwater pollution, especially for nitrogen (N) pollution. In this paper, an
experiment was conducted in a direct-seeded paddy field under traditional
continuously flooded irrigation (CFI). The water movement and N transport and
transformation were simulated via the Hydrus-1D model, and the model was
calibrated using field measurements. The model had a total water balance error of
0.236 cm and a relative error (error/input total water) of 0.23%. For the solute
transport model, the N balance error and relative error (error/input total N)
were 0.36 kg ha-1 and 0.40%, respectively. The study results indicate that the
plow pan plays a crucial role in vertical water movement in paddy fields. Water
flow was mainly lost through surface runoff and underground drainage, with
proportions to total input water of 32.33 and 42.58%, respectively. The water
productivity in the study was 0.36 kg m-3. The simulated N concentration results
revealed that ammonia was the main form in rice uptake (95% of total N uptake),
and its concentration was much larger than for nitrate under CFI. Denitrification
and volatilization were the main losses, with proportions to total consumption of
23.18 and 14.49%, respectively. Leaching (10.28%) and surface runoff loss (2.05%)
were the main losses of N pushed out of the system by water. Hydrus-1D simulation
was an effective method to predict water flow and N concentrations in the three
different forms. The study provides results that could be used to guide water and
fertilization management and field results for numerical studies of water flow
and N transport and transformation in the future.
PMID- 28493193
TI - The first survey of airborne trace elements at airport using moss bag technique.
AB - Air traffic represents an important way of social mobility in the world, and many
ongoing discussions are related to the impacts that air transportation has on
local air quality. In this study, moss Sphagnum girgensohnii was used for the
first time in the assessment of trace element content at the international
airport. The moss bags were exposed during the summer of 2013 at four sampling
sites at the airport 'Nikola Tesla' (Belgrade, Serbia): runway (two), auxiliary
runway and parking lot. According to the relative accumulation factor (RAF) and
the limit of quantification of the moss bag technique (LOQT), the most abundant
elements in the samples were Zn, Na, Cr, V, Cu and Fe. A comparison between the
element concentrations at the airport and the corresponding values in different
land use classes (urban central, suburban, industrial and green zones) across the
city of Belgrade did not point out that the air traffic and associated activities
significantly contribute to the trace element air pollution. This study
emphasised an easy operational and robust (bio)monitoring, using moss bags as a
suitable method for assessment of air quality within various microenvironments
with restriction in positioning referent instrumental devices.
PMID- 28493194
TI - Effectiveness of quercetin in an experimental rat model of allergic rhinitis.
AB - We aimed to investigate whether quercetin had a therapeutic effect in an
experimental rat model of allergic rhinitis. The study was conducted with 35
rats, which were randomly assigned into 4 groups: group 1 (n = 5), sham group;
group 2 (quercetin group, n = 10) received 80 mg/kg day quercetin; group 3
(steroid group, n = 10) received steroid (mometasone furoate); and group 4
(control group, n = 10), received ovalbumin alone. Rats were sensitized by
administration of ovalbumin on alternate days over 14 days via an intraperitoneal
route. On day 15, in addition to ovalbumin via an intranasal route, quercetin and
steroid were given over 7 days to the corresponding groups. All rats were then
sacrificed and nasal turbinates were evaluated histopathologically, and serum
total IgE and ovalbumin (OVA)-specific IgE values were measured before and after
treatment. A significant increase in OVA-specific IgE values was detected in all
groups except sham group. A significant increase was detected in post-treatment
total IgE levels in the control group, while no significant change was detected
in the sham, quercetin, and intranasal steroid groups. On histopathological
evaluation, it was observed that findings of allergic rhinitis were suppressed in
the quercetin group when compared to the control group. In immunohistochemical
evaluation, it was detected that COX-2 and VIP expressions were weaker in the
quercetin group compared to the control group. Based on these findings, we
conclude that quercetin was effective in allergic rhinitis induced by ovalbumin
in rats both histopathologically and serologically.
PMID- 28493195
TI - uDISE model: a universal drug-induced sedation endoscopy classification system
part 1.
AB - Drug-induced sedation endoscopy (DISE) classification systems play a significant
role in clinical analysis based on DISE findings, treatment decision process,
treatment planning process and fundamentally in treatment outcomes. However,
there is a major problem: there is no universally agreed DISE classification
system. Hence, for the same DISE examination different DISE classification
systems can be used to: assess anatomic findings, decide and plan different
treatments. Hence, this leads to different treatment outcomes. The key objective
of this study is to propose uDISE model: universal drug-induced sedation
endoscopy (DISE) classification system. Set theory and relational mapping was
used to develop a DISE classification system based on anatomical
structures/level; degree of severity; and configuration of obstruction and its
relationship with existing DISE classification systems. uDISE model consists of
seven anatomical sites (nose, velum, tonsils, lateral pharyngeal wall/oropharynx,
tongue base, epiglottis and larynx), three degrees of obstructive severity (none,
partial and complete), three configurations of obstruction (anteroposterior,
lateral and circumferential) and a severity index. uDISE model was mapped to four
existing DISE classification systems: Pringle and Croft grading system, VOTE,
NOHL and P-T-L-Tb-E. uDISE model provides a methodology for mapping different
DISE findings based on different classification systems into one common DISE
assessments format. This provides a framework for comparing different DISE
assessments, treatment plan and treatment outcome irrespective of DISE
classification system used. Further research is required to establish a complete
relational mapping between uDISE model and other existing DISE classification
systems.
PMID- 28493196
TI - Head and neck reconstruction in the elderly patient: a safe procedure?
AB - Demographic changes strongly affect industrialized countries. While free tissue
transfer was initially believed to be beneficial only for younger patients, there
is an increasing number of elderly patients requiring microvascular operations in
our aging society. Medical and surgical risks for head and neck cancer patients
over a certain age who undergo free tissue transfer has hardly been investigated.
A retrospective mono-center cohort study was performed. All patients with the age
75 or higher undergoing microvascular operations were reviewed. Patient
characteristics including the ASA-status, the ACE-27-score, flap survival and
postoperative medical and surgical complications were evaluated. The Clavien
Dindo-classification system for postoperative complications was applied to assess
the severity of the complications. A total of 31 patients with an average age of
78.8 years were included. 4 patients suffered from venous congestion and had to
undergo revision surgery. All flaps could successfully be salvaged. Higher ASA
status and ACE-score were significantly associated with postoperative medical and
surgical complications and a higher severity of the complications. However ,
neither age nor operating time had influence on the complication rate.
Microvascular free tissue transfer can be performed with a high degree of
security in selected elderly patients. However, serious medical complications
remain a concern, correlating strongly with high ASA and ACE-score. Careful
patient selection is mandatory to reduce complications to a minimum.
PMID- 28493197
TI - Risk factors for ventilator-associated pneumonia among patients undergoing major
oncological surgery for head and neck cancer.
AB - Patients undergoing major oncological surgery for head and neck cancer (SHNC)
have a particularly high risk of nosocomial infections. We aimed to identify risk
factors for ventilator-associated pneumonia (VAP) in patients undergoing SHNC.
The study included 465 patients who underwent SHNC between June 2011 and June
2014. The rate of VAP, risk factors for VAP, and biological aspects of VAP were
retrospectively evaluated. The incidence of VAP was 19.6% (n = 95) in patients
who required more than 48 h of mechanical ventilation. Staphylococcus (37.7%),
Enterobacteriaceae (32.1%), Pseudomonas (20.8%), and Haemophilus (16.9%) were the
major bacterial species that caused VAP. The independent risk factors for VAP
were advanced age, current smoking status, chronic obstructive pulmonary disease,
and a higher simplified acute physiology score system II upon admission.
Tracheostomy was an independent protective factor for VAP. The median length of
stay in the ICU for patients who did or did not develop VAP was 8.0 and 6.5 days,
respectively (P = 0.006). Mortality among patients who did or did not develop VAP
was 16.8% and 8.4%, respectively (P < 0.001). The potential economic impact of
VAP was high because of the significantly extended duration of ventilation. A
predictive regression model was developed with a sensitivity of 95.3% and a
specificity of 69.4%. VAP is common in patients who are undergoing SHNC and who
require more than 48 h of mechanical ventilation. Therefore, innovative
preventive measures should be developed and applied in this high-risk population.
PMID- 28493198
TI - Risk factors of prognosis after acute kidney injury in hospitalized patients.
AB - The risk factors, especially laboratory indicators, of prognosis after acute
kidney injury (AKI) remain unclear. We conducted a retrospective survey of
Chinese People's Liberation Army General Hospital from January 1, 2012 to
December 31, 2012 according to the AKI diagnosis standard issued by Kidney
Disease Improving Global Outcomes. The epidemiological features and factors
influencing hospital mortality and renal function recovery were evaluated through
logistic regression analysis. Among 77 662 cases of hospitalized patients, 1387
suffered from AKI. The incidence rate and mortality of AKI were 1.79% and 14.56%,
respectively. Multivariate logistic regression analysis revealed that high AKI
stage, age greater than 80 years, neoplastic disease, low cardiac output,
increased white blood cell count, and decreased platelet count and serum albumin
levels were the risk factors affecting the mortality of AKI patients. Conversely,
body mass index between 28 and 34.9 was a protective factor. Increased AKI stage,
tumor disease, post-cardiopulmonary resuscitation, and RRT were the risk factors
of renal function recovery upon discharge. In addition to traditional risk
factors, white blood cell count, platelet count, albumin, and BMI were the
predictors of the mortality of AKI patients. No laboratory indicators were found
to be the risk factors of renal function recovery in AKI patients.
PMID- 28493199
TI - Selenium-Chromium(VI) Interaction Regulates the Contents and Correlations of
Trace Elements in Chicken Brain and Serum.
AB - This study aims to investigate the contents of trace elements in the brain and
serum of male chickens and the effect of selenium-chromium(VI) interaction. A
chronic experimental model was established by supplementing 22.14 mg/kg K2Cr2O7
with 0.00, 0.31, 0.63, 1.25, 2.50, and 5.00 mg/kg Na2SeO3 mg/kg B.W. to water for
chicken daily. After 14, 28, and 42 days of exposure to the solution, the brain
and serum of chickens from each group were collected to detect the levels of Ca,
Cu, Mn, Fe, Zn, and Mg by inductively coupled plasma mass spectrometer (ICP-MS).
Cr(VI) time-dependently accumulated in the brain and serum. The contents of Cr
increased both in the brain and serum with prolonged exposure. Cr contents in the
brain and serum decreased in all Se groups compared with those in only Cr-treated
groups. Ca contents decreased with prolonged exposure and increasing Se dosage.
The contents of Cu and Mn increased on the 28th day but decreased on the 42nd day
in the brain and serum. Fe and Zn contents decreased in the serum under prolonged
exposure and increased on the 28th day but decreased on the 42nd day in the
brain. Cr exposure did not significantly affect Mg contents in the brain but
slightly decreased those in the serum. Therefore, appropriate doses of Se
affected Cr accumulation, leading to adjustments in the contents and correlations
of trace elements.
PMID- 28493200
TI - Reducing radiation exposure from nuclear myocardial perfusion imaging: Time to
act is now.
PMID- 28493201
TI - Nuclear cardiology practice in Spain.
AB - BACKGROUND: In Spain, nuclear cardiology (NC) procedures represent the second
most frequently performed studies in nuclear medicine (NM) centers. METHODS: The
NC Working Group of the Spanish Society of Nuclear Medicine and Molecular Imaging
invited NM departments across the country to answer an online questionnaire
regarding 2014 activity. RESULTS: Data on 40,161 patients from 42 centers were
collected. The responding public centers served 39% of Spain's population. The
estimated NC activity for public hospitals was 2 studies/1,000 population/year.
Of all the NC procedures, 69% were SPECT myocardial perfusion imaging (MPI), 17%
equilibrium ventriculography, 12% 18F-FDG PET, 1.3% first pass ventriculography,
and <1% innervation and amyloidosis imaging, respectively. The most frequent NC
study was a 99mTc tracer, exercise, 2-day MPI ECG-gated SPECT ordered by a
cardiologist for diagnosis in an outpatient with 21 days of mean waiting time,
the stress phase being supervised by both a cardiologist and a NM physician, with
a NM physician writing a complete report. CONCLUSIONS: A major challenge for NC
in Spain is the gradual adoption of high-sensitivity, low-dose-dedicated cardiac
SPECT cameras and the broadening of cardiac PET utilization with more cameras,
and the availability of MPI tracers alongside the viability/inflammation setup.
PMID- 28493202
TI - Is measurement of renal function necessary for all trauma patients before
iodinated contrast administration?
AB - PURPOSE: The purpose of this study was to identify factors at the time of
presentation which could quickly exclude or identify renal dysfunction in blunt
trauma patients, thus negating serum measurement of renal function prior to
contrast-enhanced imaging and expediting care. METHODS: Patients, >18 years old,
without renal failure, presenting after blunt trauma, with serum creatinine
measured at presentation, were retrospectively studied at a single center.
Variables recorded at presentation including vitals, mechanism, and past medical
history were analyzed using multivariate regression analysis to identify
independent predictors of abnormal renal function. RESULTS: From 2009 to 2015, a
total of 1099 patients met the inclusion criteria. Of those, 75 (6.8%) had renal
dysfunction at presentation. Patients with renal dysfunction had a mean age of
74.3 (SD 15.5) years old, and 57.3% were male. Multivariate analysis identified
independent predictors of renal dysfunction at presentation as age >= 61 (p <
0.001), hypotension (p = 0.02), and diabetes (p = 0.02). The presence of a single
identified factor had an 85% sensitivity for renal dysfunction and a 98.5%
negative predictive value. CONCLUSIONS: Impaired renal function at presentation
was infrequent in our trauma cohort. Trauma patients who were normotensive, under
the age of 61, and without diabetes were unlikely to have impaired renal function
at presentation. In the urgent setting of trauma, patients without these
comorbidities are likely safe to forgo screening of renal function prior to
contrast-enhanced imaging.
PMID- 28493204
TI - Analysis of molecular and (di)atomic dual-descriptor functions and matrices.
AB - In this work, the dual-descriptor is studied in matrix form [Formula: see text]
and both coordinates condensed to atoms, resulting in atomic and diatomic (or
where applicable, bond) condensed single values. This double partitioning method
of the dual-descriptor matrix is proposed within the Hirshfeld-I atoms-in
molecule framework although it is easily extended to other atoms-in-molecules
methods. Diagonalizing the resulting atomic and bond dual-descriptor matrices
gives eigenvalues and eigenvectors describing the reactivity of atoms and bonds.
The dual-descriptor function is the diagonal element of the underlying matrix.
The extra information contained in the atom and bond resolution is highlighted
and the effect of choosing either the fragment of molecular response or response
of molecular fragment approach is quantified. Graphical Abstract Atom and bond
condensed dual descriptor matrices and functions are derived from molecular ones
using Hirshfeld-I atoms in molecules weight functions.
PMID- 28493203
TI - Dissection of broad-spectrum resistance of the Thai rice variety Jao Hom Nin
conferred by two resistance genes against rice blast.
AB - BACKGROUND: Rice (Oryza sativa) is one of the most important food crops in the
world. Rice blast, caused by the fungal pathogen Magnaporthe oryzae, is one of
the most destructive rice diseases worldwide. To effectively cope with this
problem, the use of rice blast resistance varieties through innovative breeding
programs is the best strategy to date. The Thai rice variety Jao Hom Nin (JHN)
showed broad-spectrum resistance against Thai rice blast isolates. Two QTLs for
blast resistance in JHN were reported on chromosome 1 (QTL1) and 11 (QTL11).
RESULTS: Monogenic lines of QTL1 (QTL1-C) and QTL11 (QTL11-C) in the CO39 genetic
background were generated. Cluster analysis based on the disease reaction pattern
of QTL1-C and QTL11-C, together with IRBLs, showed that those two monogenic lines
were clustered with IRBLsh-S (Pish) and IRBL7-M (Pi7), respectively. Moreover,
sequence analysis revealed that Pish and Pi7 were embedded within the QTL1 and
QTL11 delimited genomic intervals, respectively. This study thus concluded that
QTL1 and QTL11 could encode alleles of Pish and Pi7, designated as Pish-J and Pi7
J, respectively. To validate this hypothesis, the genomic regions of Pish-J and
Pi7-J were cloned and sequenced. Protein sequence comparison revealed that Pish-J
and Pi7-J were identical to Pish and Pi7, respectively. The holistic disease
spectrum of JHN was found to be exactly attributed to the additive ones of both
QTL1-C and QTL11-C. CONCLUSION: JHN showed broad spectrum resistance against Thai
and Philippine rice blast isolates. As this study demonstrated, the combination
of two resistance genes, Pish-J and Pi7-J, in JHN, with each controlling broad
spectrum resistance to rice blast disease, explains the high level of resistance.
Thus, the combination of Pish and Pi7 can provide a practical scheme for breeding
durable resistance in rice against rice blast disease.
PMID- 28493206
TI - Switching Effects in Molecular Electronic Devices.
AB - The creation of molecular electronic switches by using smart molecules is of
great importance to the field of molecular electronics. This requires a
fundamental understanding of the intrinsic electron transport mechanisms, which
depend on several factors including the charge transport pathway, the molecule
electrode coupling strength, the energy of the molecular frontier orbitals, and
the electron spin state. On the basis of significant progresses achieved in both
experiments and theory over the past decade, in this review article we focus on
new insights into the design and fabrication of different molecular switches and
the corresponding switching effects, which is crucial to the development of
molecular electronics. We summarize the strategies developed for single-molecule
device fabrication and the mechanism of these switching effects. These analyses
should be valuable for deeply understanding the switching effects in molecular
electronic devices.
PMID- 28493205
TI - Development of the life impact burn recovery evaluation (LIBRE) profile:
assessing burn survivors' social participation.
AB - PURPOSE: Measuring the impact burn injuries have on social participation is
integral to understanding and improving survivors' quality of life, yet there are
no existing instruments that comprehensively measure the social participation of
burn survivors. This project aimed to develop the Life Impact Burn Recovery
Evaluation Profile (LIBRE), a patient-reported multidimensional assessment for
understanding the social participation after burn injuries. METHODS: 192
questions representing multiple social participation areas were administered to a
convenience sample of 601 burn survivors. Exploratory factor analysis and
confirmatory factor analysis (CFA) were used to identify the underlying structure
of the data. Using item response theory methods, a Graded Response Model was
applied for each identified sub-domain. The resultant multidimensional LIBRE
Profile can be administered via Computerized Adaptive Testing (CAT) or fixed
short forms. RESULTS: The study sample included 54.7% women with a mean age of
44.6 (SD 15.9) years. The average time since burn injury was 15.4 years (0-74
years) and the average total body surface area burned was 40% (1-97%). The CFA
indicated acceptable fit statistics (CFI range 0.913-0.977, TLI range 0.904
0.974, RMSEA range 0.06-0.096). The six unidimensional scales were named:
relationships with family and friends, social interactions, social activities,
work and employment, romantic relationships, and sexual relationships. The
marginal reliability of the full item bank and CATs ranged from 0.84 to 0.93,
with ceiling effects less than 15% for all scales. CONCLUSIONS: The LIBRE Profile
is a promising new measure of social participation following a burn injury that
enables burn survivors and their care providers to measure social participation.
PMID- 28493208
TI - In memory of Professor Aldo Isidori.
PMID- 28493207
TI - New Azulene-Type Sesquiterpenoids from the Fruiting Bodies of Lactarius
deliciosus.
AB - In the 1H NMR-guided fractionation of extracts from the edible mushroom Lactarius
deliciosus, two new azulene-type sesquiterpenoids, 7-isopropenyl-4-methyl-azulene
1-carboxylic acid (1) and 15-hydroxy-3,6-dihydrolactarazulene (2), together with
seven known compounds were characterized. Their structures were determined on
basis of spectroscopic evidence, as well as by comparing with literature data.
Amongst the known metabolites, the 13C NMR assignment of 15-hydroxy-6,7
dihydrolactarazulene (3) is reported here for the first time. Moreover, 7-acetyl
4-methylazulene-1-carbaldehyde (5) displayed a moderate antibacterial activity
against Staphylococcus aureus. *Digital image of L. deliciosus. Retrieved March
17, 2017 from
https://upload.wikimedia.org/wikipedia/commons/e/e3/Lactarius_deliciosus_1_(1).jp
.
PMID- 28493209
TI - Erratum, corrigenda et emendatio or "mistake, correction and amendment".
PMID- 28493210
TI - In search of the optimal wound dressing material following total hip and knee
arthroplasty: a systematic review and meta-analysis.
AB - BACKGROUND: Various types of dressing materials are available for wound care
following hip and knee arthroplasty. However, it is unclear if one material is
more beneficial than the others in terms of wound complications and fluid
handling capacity. RESEARCH QUESTIONS: We performed a meta-analysis of randomized
controlled trials comparing alternative wound dressing materials for the post
operative management of wounds following THA and TKA with respect to (1)
incidence of wound complications including infection and (2) fluid handling
capacity. METHODS: Randomized controlled trials comparing alternative dressing
materials, for post-operative management of wounds following TKA and THA were
included in the review. Databases searched included the MEDLINE and the EMBASE
from inception to February 2017. Two authors performed study selection, risk of
bias assessment and data extraction. Where levels of clinical and statistical
heterogeneity permitted, data were pooled for meta-analysis. RESULTS: Twelve
randomized trials with data for the primary outcome were identified. Data were
available for meta-analysis for two comparisons. Wounds managed with film
dressings (odds ratio, 0.35; 95% confidence interval [CI], 0.21-0.57) or with
hydrofiber dressings (odds ratio, 0.28; 95% confidence interval [CI], 0.20-0.40)
were significantly less likely to have wound complications than those managed
with passive dressings. There was no evidence that any dressing significantly
reduced surgical-site infection rates compared with any other dressing.
Hydrofibre dressings showed better fluid handling capacity than passive dressings
in terms of mean number of dressing changes (mean difference 1.36; 95% confidence
interval [CI], 0.15-2.57) and number of patients requiring early dressing change
(odds ratio, 8.60; 95% confidence interval [CI], 4.68-15.83). CONCLUSION: The
evidence available in the current literature suggests that advanced dressings
such as film and Hydrofibre dressings have fewer wound complications and better
fluid handling capacity. However, insufficient evidence is available to determine
whether the use of these advanced dressings reduce periprosthetic joint
infection.
PMID- 28493212
TI - Composite Bioscaffolds Incorporating Decellularized ECM as a Cell-Instructive
Component Within Hydrogels as In Vitro Models and Cell Delivery Systems.
AB - Decellularized tissues represent promising biomaterials, which harness the innate
capacity of the tissue-specific extracellular matrix (ECM) to direct cell
functions including stem cell proliferation and lineage-specific differentiation.
However, bioscaffolds derived exclusively from decellularized ECM offer limited
versatility in terms of tuning biomechanical properties, as well as cell-cell and
cell-ECM interactions that are important mediators of the cellular response. As
an alternative approach, in the current chapter we describe methods for
incorporating cryo-milled decellularized tissues as a cell-instructive component
within a hydrogel carrier designed to crosslink under mild conditions. This
composite strategy can enable in situ cell encapsulation with high cell
viability, allowing efficient seeding with a homogeneous distribution of cells
and ECM. Detailed protocols are provided for the effective decellularization of
human adipose tissue and porcine auricular cartilage, as well as the cryo-milling
process used to generate the ECM particles. Further, we describe methods for
synthesizing methacrylated chondroitin sulphate (MCS) and for performing UV
initiated and thermally induced crosslinking to form hydrogel carriers for
adipose and cartilage regeneration. The hydrogel composites offer great
flexibility, and the hydrogel phase, ECM source, particle size, cell type(s) and
seeding density can be tuned to promote the desired cellular response. Overall,
these systems represent promising platforms for the development of tissue
specific 3-D in vitro cell culture models and in vivo cell delivery systems.
PMID- 28493211
TI - What mechanisms are associated with tibial component failure after kinematically
aligned total knee arthroplasty?
AB - PURPOSE: Eight patients treated with kinematically-aligned (KA) total knee
arthroplasty (TKA) presented with tibial component failure. We determined whether
radiographic measurements and clinical characteristics are different between
patients with and without tibial component failure to identify mechanisms of
failure and strategies to reduce the risk. METHODS: Out of 3,212 primary TKAs
(2,725 TKAs with a two-year minimum follow up), of which all were performed with
KA, eight patients presented with tibial component failure. Radiographic
measurements, clinical characteristics (e.g. age, gender, BMI, etc.), revision
surgical records, and Oxford knee scores were compared to control cohort patients
matched 1:3. RESULTS: Tibial component failure presented at an average of 28 +/-
15 months after primary TKA. Patients with tibial component failure had a 6 kg/m2
greater body mass index (p = 0.034) and 5 degrees greater posterior slope of the
tibia component (p = 0.002) than controls. Final follow-up averaged 56 +/- 19
months after the primary TKA and 28 +/- 24 months after the revision TKA. The
final Oxford knee score was 39 +/- 4.6 for patients with tibial component failure
and 44 +/- 6.5 for the controls (p = 0.005). CONCLUSIONS: The incidence of tibial
component failure after KA TKA was 0.3% and was caused by posterior subsidence or
posterior edge wear and not varus subsidence. The strategy for lowering the risk
of tibial component failure when performing KA is to set the tibial component
parallel to the flexion-extension plane (slope) and varus-valgus plane of the
native joint line.
PMID- 28493213
TI - 3D-Printing Composite Polycaprolactone-Decellularized Bone Matrix Scaffolds for
Bone Tissue Engineering Applications.
AB - Millions of patients worldwide require bone grafts for treatment of large,
critically sized bone defects from conditions such as trauma, cancer, and
congenital defects. Tissue engineered (TE) bone grafts have the potential to
provide a more effective treatment than current bone grafts since they would
restore fully functional bone tissue in large defects. Most bone TE approaches
involve a combination of stem cells with porous, biodegradable scaffolds that
provide mechanical support and degrade gradually as bone tissue is regenerated by
stem cells. 3D-printing is a key technique in bone TE that can be used to
fabricate functionalized scaffolds with patient-specific geometry. Using 3D
printing, composite polycaprolactone (PCL) and decellularized bone matrix (DCB)
scaffolds can be produced to have the desired mechanical properties, geometry,
and osteoinductivity needed for a TE bone graft. This book chapter will describe
the protocols for fabricating and characterizing 3D-printed PCL:DCB scaffolds.
Moreover, procedures for culturing adipose-derived stem cells (ASCs) in these
scaffolds in vitro will be described to demonstrate the osteoinductivity of the
scaffolds.
PMID- 28493214
TI - Theoretical-Experimental Photophysical Investigations of the Solvent Effect on
the Properties of Green- and Blue-Light-Emitting Quinoline Derivatives.
AB - This paper describes the investigations on the solvatochromic effect and the
photophysical properties of quinoline derivatives, compounds with potential
applicability in optoelectronic devices. Using an experimental and theoretical
approach, the effect of the solvent and the insertion of the phenyl, nitro, amino
and dimethylamino group in the quinoline backbone were investigated. The use of
Density Functional Theory (DFT) calculations provided the bases for the
understanding of the energetic transitions observed in the absorption and
fluorescence experiments. In general, it was observed a change in the wavelength
of maximum absorption and fluorescence quantum yield of the studied compounds
caused by the substituents in the quinoline core. This effect was correlated with
the solvent dielectric constants.
PMID- 28493215
TI - Cervical disc replacement surgery: indications, technique, and technical pearls.
AB - PURPOSE OF REVIEW: Cervical disc replacement (CDR) is a surgical option for
appropriately indicated patients, and high success rates have been reported in
the literature. Complications and failures are often associated with patient
indications or technical variables, and the goal of this review is to assist
surgeons in understanding these factors. RECENT FINDINGS: Several investigations
have been published in the last 5 years supporting the use of CDR in specific
patient populations. CDR has been shown to be comparable or favorable to anterior
cervical discectomy and fusion in several meta-analyses and mid-term follow-up
studies. CDR was developed as a technique to preserve motion following a
decompression procedure while minimizing several of the complications associated
with fusion and posterior cervical spine procedures. Though success with cervical
fusion and posterior foraminotomy has been well documented in the literature,
high rates of mid- and long-term complications have been clearly established. CDR
has also been associated with several complications and challenges with regard to
surgical technique, though improvements in implant design have lead to an
increase in utilization. Several devices currently exist and vary in terms of
material, design, and outcomes. This review paper discusses indications, surgical
technique, and technical pearls and reviews the CDR devices currently available.
PMID- 28493216
TI - Appropriateness of Oral Anticoagulants for the Long-Term Treatment of Atrial
Fibrillation in Older People: Results of an Evidence-Based Review and
International Consensus Validation Process (OAC-FORTA 2016).
AB - BACKGROUND: Age appropriateness of anticoagulants for stroke prevention in atrial
fibrillation is uncertain. OBJECTIVE: To review oral anticoagulants for the
treatment of atrial fibrillation in older (age >65 years) people and to classify
appropriate and inappropriate drugs based on efficacy, safety and tolerability
using the Fit-fOR-The-Aged (FORTA) classification. METHODS: We performed a
structured comprehensive review of controlled clinical trials and summaries of
individual product characteristics to assess study and total patient numbers,
quality of major outcome data and data of geriatric relevance. The resulting
evidence was discussed in a round table with an interdisciplinary panel of ten
European experts. Decisions on age appropriateness were made using a Delphi
process. RESULTS: For the eight drugs included, 380 citations were identified.
The primary outcome results were reported in 32 clinical trials with explicit and
relevant data on older people. Though over 24,000 patients aged >75/80 years were
studied for warfarin, data on geriatric syndromes were rare (two studies
reporting on frailty/falls/mental status) and missing for all other compounds.
Apixaban was rated FORTA-A (highly beneficial). Other non-vitamin K antagonist
oral anticoagulants (including low/high-intensity dabigatran and high-intensity
edoxaban) and warfarin were assigned to FORTA-B (beneficial). Phenprocoumon,
acenocoumarol and fluindione were rated FORTA-C (questionable), mainly reflecting
the absence of data. CONCLUSIONS: All non-vitamin K antagonist oral
anticoagulants and warfarin were classified as beneficial or very beneficial in
older persons (FORTA-A or -B), underlining the overall positive assessment of the
risk/benefit ratio for these drugs. For other vitamin-K antagonists regionally
used in Europe, the lack of evidence should challenge current practice.
PMID- 28493217
TI - What Is the Mid-term Failure Rate of Revision ACL Reconstruction? A Systematic
Review.
AB - BACKGROUND: When anterior cruciate ligament (ACL) reconstruction fails, a
revision procedure may be performed to improve knee function, correct
instability, and allow return to activities. The results of revision ACL
reconstruction have been reported to produce good but inferior patient-reported
and objective outcomes compared with primary ACL reconstruction, but the degree
to which this is the case varies widely among published studies and may be
influenced by heterogeneity of patients, techniques, and endpoints assessed. For
those reasons, a systematic review may provide important insights.
QUESTIONS/PURPOSES: In a systematic review, we asked: (1) What is the proportion
of revision ACL reconstruction cumulative failures defined as rerupture or
objective failure using prespecified clinical criteria at mean followup of at
least 5 years? (2) What are the most common complications of revision ACL
reconstruction? METHODS: A systematic review was performed by searching
PubMed/Medline, EMBASE, and CENTRAL. We included studies that reported the
clinical evaluation of revision ACL reconstruction with Lachman test, pivot shift
test, side-to-side difference with KT-1000/2000 arthrometer, and with a mean
followup of at least 5 years. We excluded studies that incompletely reported
these outcomes, that reported only reruptures, or that were not in the English
language. Extracted data included the number of graft reruptures and objective
clinical failure, defined as a knee that met one of the following endpoints:
Lachman test Grade II to III, pivot shift Grade II to III, KT-1000/2000 > 5-mm
difference, or International Knee Documentation Committee Grade C or D. For each
study, we determined the proportion of patients who had experienced a rupture of
the revision ACL graft as well as the proportion of patients who met one or more
of our clinical failure endpoints. Those proportions were summed for each study
to generate a percentage of patients who met our definition of cumulative
failure. Complications and reoperations were recorded but not pooled as a result
of inconsistency of reporting and heterogeneity of populations across the
included studies. Of the 663 screened studies, 15 articles were included in the
systematic review. Because one study reported two separate groups of patients
with different treatments, 16 case series were considered in the evaluation.
RESULTS: The proportion of reruptures (range, 0%-25%) was > 5% in only four of 16
series and > 10% in only one of them. The objective clinical failures (range, 0%
82%) was > 5% in 15 of 16 series and > 10% in 12 of them. The proportion exceeded
20% in five of 16 series. The cumulative failures (range, 0%-83%) was > 5% in all
except one series and > 10% in 12 of 16 series; five series had a cumulative
failure proportion > 20%. The most frequent complications were knee stiffness and
anterior knee pain, whereas reoperations were primarily debridement and
meniscectomies. CONCLUSIONS: Considering rerupture alone as a failure endpoint in
patients who have undergone revision ACL reconstruction likely underestimates the
real failure rate, because the percentage of failures noticeably increases when
objective criteria are also considered. Whether patient-reported and subjective
scores evaluating knee function, level of activity, satisfaction, and pain might
also contribute to the definition of failure may be the focus of future studies.
LEVEL OF EVIDENCE: Level IV, therapeutic study.
PMID- 28493218
TI - Curriculum Overhaul in Psychiatric Residency: An Innovative Approach to Revising
the Didactic Lecture Series.
PMID- 28493219
TI - A critical appraisal of the cost effectiveness of laparoscopic colorectal surgery
for oncological and non-oncological resections.
AB - The aim of this study was to critically appraise the cost effectiveness of the
laparoscopic colorectal (LCRS) surgery using published randomised, control trials
(RCTs). Published RCTs comparing the cost effectiveness of LCRS with conventional
open surgery were selected from the search of standard electronic databases and
the extracted data were analysed using the statistical software RevMan 5.3. Seven
RCTs on 2197 patients reported the cost effectiveness of the LCRS. There was
significant heterogeneity (tau 2 = 161,772.25, chi 2 = 166.69, df = 6, p =
0.00001, I 2 = 96%) among included randomised, controlled trials. In the random
effects model analysis (MD 320.37, 95% CI -38.21, 678.95, z = 1.75, p < 0.08),
the LCRS was costing L320.37 more than open colorectal resection but it failed to
reach the statistical significance indicating that LCRS is as much cost effective
as the open approach. LCRS is a cost effective intervention and should be offered
routinely to all patients requiring colorectal resections provided the resources
and expertise are available.
PMID- 28493220
TI - Continuous intraoperative neural monitoring in thyroid surgery: a Mexican
experience.
AB - Intraoperative continuous neural monitoring (C-IONM) during thyroid surgery has
been recognized as a useful tool to identify and confirm recurrent laryngeal
nerve integrity. The aim of the present study is to analyze electromyographic
features and thresholds for normal vocal fold function in our initial experience
with C-IONM in thyroid surgery. C-IONM was utilized in 57 patients who underwent
thyroid surgery between July 2012 and December 2015. EMG parameters were analyzed
looking for potential predictors of postoperative vocal fold dismotility. There
were 54 females (94.7%) and 3 males (5.3%) with a mean age of 46.7 +/- 11.6
years. C-IONM was successfully registered in 89 of 107 nerves at risk (83.1%).
Mean basal amplitude was 727.31 +/- 471.25 MUV and mean final amplitude was
650.27 +/- 526.87 MUV (P = 0.095, CI 95% 13.83-167.91). Mean basal latency was
5.23 +/- 1.42 mS and mean final latency was 5.18 +/- 1.50 mS (P = 0.594, CI 95%
0.39-0.24). Four patients had transient postoperative vocal fold paresis. None of
these four patients had loss of signal (LOS), three had transient decrease in
amplitude, and one had a normal registry throughout the operation. C-IONM is a
useful tool to identify patients in whom intraoperative RLN is at risk during
surgery. Final amplitude above 500 MUV and no LOS is associated with RLN
integrity and normal postoperative vocal fold function.
PMID- 28493222
TI - [Twelve years of the S3 guideline Fibromyalgia Syndrome-a never-ending war?]
PMID- 28493221
TI - Radical surgery for gastric cancer in octogenarian patients.
AB - To valuate feasibility and results of radical surgery in octogenarian patients
with gastric cancer. We collected data on 60 patients that underwent gastrectomy
with an R0 resection at our Institution from 2010 to 2015. Patients were divided
into two groups: octogenarian (OG) (n = 26), consisting of patients aged 80-89
years, and younger (YG) (n = 34), consisting of patients under 80 years of age.
All patients were treated with total or subtotal gastrectomy with
lymphadenectomy. A D2-lymphadenectomy was performed in 11 and 24 patients, a D1+
in 5 and 4, a D1 in 8 and 6, and a D0 in 2 and 0 cases in OG and YG respectively.
The overall morbidity rate was 42.3% (11/26) in OG and 29.4% (10/34) in YG, while
90-days mortality was observed in four (15.4%) and one (2.9%) patients in OG and
YG, respectively. The median hospital stay was 9 days (2-31) and 9.5 days (6-66)
in OG and YG, respectively. Gastrectomy with radical resection and limited
lymphadenectomy should be recommended for octogenarian patients with good
performance status and low co-morbidity.
PMID- 28493223
TI - [Physiotherapy, occupational therapy and physical therapy in fibromyalgia
syndrome : Updated guidelines 2017 and overview of systematic review articles].
AB - BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF
number 145/004, was scheduled for April 2017. METHODS: The guidelines were
developed by 13 scientific societies and 2 patient self-help organizations
coordinated by the German Pain Society. Working groups (n =8) with a total of 42
members were formed balanced with respect to gender, medical expertise, position
in the medical or scientific hierarchy and potential conflicts of interest. A
literature search for systematic reviews of randomized, controlled trials on
physiotherapy, occupational therapy and physical therapy from December 2010 to
May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus
databases. Levels of evidence were assigned according to the classification
system of the Oxford Centre for Evidence-Based Medicine version 2009. The
strength of recommendations was achieved by multiple step formalized procedures
to reach a consensus. Efficacy, risks, patient preferences and applicability of
available therapies were weighed up against each other. The guidelines were
reviewed and approved by the board of directors of the societies engaged in the
development of the guidelines. RESULTS AND CONCLUSION: Low to moderate intensity
endurance and strength training are strongly recommended. Chiropractic, laser
therapy, magnetic field therapy, massage and transcranial magnetic stimulation
are not recommended.
PMID- 28493224
TI - [Psychotherapy and psychological procedures for fibromyalgia syndrome : Updated
guidelines 2017 and overview of systematic review articles].
AB - BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF
number 145/004, was scheduled for April 2017. METHODS: The guidelines were
developed by 13 scientific societies and 2 patient self-help organizations
coordinated by the German Pain Society. Working groups (n =8) with a total of 42
members were formed balanced with respect to gender, medical expertise, position
in the medical or scientific hierarchy and potential conflicts of interest. A
systematic search of the literature for systematic reviews of randomized,
controlled studies on psychological and psychotherapeutic procedures from
December 2010 to May 2016 was performed in the Cochrane library, MEDLINE,
PsycINFO and Scopus databases. Levels of evidence were assigned according to the
classification system of the Oxford Centre for Evidence-Based Medicine version
2009. The strength of recommendations was achieved by multiple step formalized
procedures to reach a consensus. Efficacy, risks, patient preferences and
applicability of available therapies were weighed up against each other. The
guidelines were reviewed and approved by the board of directors of the societies
engaged in the development of the guidelines. RESULTS AND CONCLUSION: Cognitive
behavioral therapies received a strong recommendation but biofeedback, guided
imagery and hypnosis received a weak recommendation.
PMID- 28493225
TI - [Definition, diagnostics and therapy of chronic widespread pain and the (so
called) fibromyalgia syndrome in children and adolescents : Updated guidelines
2017].
AB - BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF
number 145/004, was scheduled for April 2017. METHODS: The guidelines were
developed by 13 scientific societies and 2 patient self-help organizations
coordinated by the German Pain Society. Working groups (n = 8) with a total of 42
members were formed balanced with respect to gender, medical expertise, position
in the medical or scientific hierarchy and potential conflicts of interest. A
search of the literature for case series (cross-sectional- and longitudinal
studies) for the topics diagnosis, etiology and pathophysiology and for
randomised controlled trials (RCT) for treatment modalities from December 2010 to
May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus
databases. Levels of evidence were assigned according to the classification
system of the Oxford Centre for Evidence-Based Medicine version 2009. The
strength of recommendations was achieved by multiple step formalized procedures
to reach a consensus. Efficacy, risks, patient preferences and applicability of
available therapies were weighed up against each other. The guidelines were
reviewed and approved by the board of directors of the societies engaged in the
development of the guidelines. RESULTS AND CONCLUSION: No consensus was achieved
in the guideline group on whether the diagnostic label "juvenile fibromyalgia"
should be used in the management of children and adolescents with chronic
widespread pain. There was consensus in the guideline group that antidepressants
and anticonvulsants should not be used to treat pain in the so-called juvenile
fibromyalgia syndrome.
PMID- 28493227
TI - [Complementary and alternative procedures for fibromyalgia syndrome : Updated
guidelines 2017 and overview of systematic review articles].
AB - BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF
number 145/004, was scheduled for April 2017. METHODS: The guidelines were
developed by 13 scientific societies and 2 patient self-help organizations
coordinated by the German Pain Society. Working groups (n =8) with a total of 42
members were formed balanced with respect to gender, medical expertise, position
in the medical or scientific hierarchy and potential conflicts of interest. A
search of the literature for systematic reviews of randomized controlled trials
of complementary and alternative therapies from December 2010 to May 2016 was
performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels
of evidence were assigned according to the classification system of the Oxford
Centre for Evidence-Based Medicine version 2009. The strength of recommendations
was formed by multiple step formalized procedures to reach a consensus. Efficacy,
risks, patient preferences and applicability of available therapies were weighed
up against each other. The guidelines were reviewed and approved by the board of
directors of the societies engaged in the development of the guidelines. RESULTS
AND CONCLUSION: Meditative movement therapies (e.g. qi gong, tai chi and yoga)
are strongly recommended. Acupuncture and weight reduction in cases of obesity
can be considered.
PMID- 28493226
TI - [Etiology and pathophysiology of fibromyalgia syndrome : Updated guidelines 2017,
overview of systematic review articles and overview of studies on small fiber
neuropathy in FMS subgroups].
AB - BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF
number 145/004, was planned for April 2017. METHODS: The guidelines were
developed by 13 scientific societies and 2 patient self-help organizations
coordinated by the German Pain Society. Working groups (n =8) with a total of 42
members were formed balanced with respect to gender, medical expertise, position
in the medical or scientific hierarchy and potential conflicts of interest. A
systematic search of the literature from December 2010 to May 2016 was performed
in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Prospective
population-based studies and systematic reviews with meta-analyses of case
control studies were taken into consideration for the statements. Levels of
evidence were assigned according to the classification system of the Oxford
Centre for Evidence-Based Medicine version 2009. The statements were generated by
multiple step formalized procedures. The guidelines were reviewed and approved by
the board of directors of the societies engaged in the development of the
guidelines. RESULTS: Current data do not enable identification of distinct
factors in the etiology and pathophysiology of fibromyalgia syndrome.
Fibromyalgia syndrome can be associated with inflammatory rheumatic diseases,
gene polymorphisms, life style factors (e.g. smoking, obesity and lack of
physical activity), depressive disorders as well as physical and sexual abuse in
childhood and adulthood. CONCLUSION: Fibromyalgia syndrome is most probably the
end result of various pathogenetic factors and pathophysiological mechanisms.
PMID- 28493228
TI - [Multimodal therapy of fibromyalgia syndrome : Updated guidelines 2017 and
overview of systematic review articles].
AB - BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF
number 145/004, was scheduled for April 2017. METHODS: The guidelines were
developed by 13 scientific societies and 2 patient self-help organizations
coordinated by the German Pain Society. Working groups (n = 8) with a total of 42
members were formed balanced with respect to gender, medical expertise, position
in the medical or scientific hierarchy and potential conflicts of interest. A
search of the literature for systematic reviews on randomized controlled trials
of multimodal therapy from December 2010 to May 2016 was performed in the
Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels of evidence were
assigned according to the classification system of the Oxford Centre for Evidence
Based Medicine version 2009. The strength of recommendations was achieved by
multiple step formalized procedures to reach a consensus. Efficacy, risks,
patient preferences and applicability of available therapies were weighed up
against each other. The guidelines were reviewed and approved by the board of
directors of the societies engaged in the development of the guidelines. RESULTS
AND CONCLUSION: The use of multimodal therapy (combination of aerobic exercise
with at least one psychological therapy) with a duration of at least 24 h is
strongly recommended for patients with severe forms of fibromyalgia.
PMID- 28493229
TI - [General treatment principles, coordination of care and patient education in
fibromyalgia syndrome : Updated guidelines 2017 and overview of systematic review
articles].
AB - BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF
number 145/004, was scheduled for April 2017. METHODS: The guidelines were
developed by 13 scientific societies and 2 patient self-help organizations
coordinated by the German Pain Society. Working groups (n =8) with a total of 42
members were formed balanced with respect to gender, medical expertise, position
in the medical or scientific hierarchy and potential conflicts of interest. A
search of the literature for systematic reviews on randomized, controlled trials
on patient education and shared decision-making from December 2010 to May 2016
was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases.
Levels of evidence were assigned according to the classification system of the
Oxford Centre for Evidence-Based Medicine version 2009. The strength of
recommendations was achieved by multiple step formalized procedures to reach a
consensus. Efficacy, risks, patient preferences, clinical and practical
applicability of available therapies were weighed up against each other. The
guidelines were reviewed and approved by the board of directors of the societies
engaged in the development of the guidelines. RESULTS AND CONCLUSION: The
diagnosis of fibromyalgia syndrome should be explicitly communicated to the
affected individual. Shared decision-making with the patient on the therapeutic
options based on individual preferences of the patient, comorbidities and the
success of previous treatment is recommended. A step-wise treatment approach
depending on the severity of fibromyalgia syndrome and the response to
therapeutic measures is recommended.
PMID- 28493230
TI - [Methodology report of the 2017 guidelines on fibromyalgia syndrome].
AB - BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF
number 145/004, was planned for April 2017. METHODS: The guidelines were
developed by 13 scientific societies and 2 patient self-help organizations
coordinated by the German Pain Society. Working groups (n = 8) with a total of 42
members were formed balanced with respect to gender, medical expertise, position
in the medical or scientific hierarchy and potential conflicts of interest.
RESULTS: A systematic search of the literature from December 2010 to May 2016 was
performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels
of evidence were assigned according to the classification system of the Oxford
Centre for Evidence-Based Medicine version 2009. The strength of recommendations
was achieved by multiple step formalized procedures to reach a consensus.
Efficacy, risks, patient preferences and applicability of therapies available
were weighed up against each other. The guidelines were reviewed and approved by
the board of directors of the societies engaged in the development of the
guidelines. CONCLUSION: The guidelines are published in several forms, i.e.
complete and short scientific versions and clinical practice and patient
versions.
PMID- 28493231
TI - [Drug therapy of fibromyalgia syndrome : Updated guidelines 2017 and overview of
systematic review articles].
AB - BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF
number 145/004, was scheduled for April 2017. METHODS: The guidelines were
developed by 13 scientific societies and 2 patient self-help organizations
coordinated by the German Pain Society. Working groups (n =8) with a total of 42
members were formed balanced with respect to gender, medical expertise, position
in the medical or scientific hierarchy and potential conflicts of interest. A
literature search for systematic reviews of randomized controlled drug trials
from December 2010 to May 2016 was performed in the Cochrane library, MEDLINE,
PsycINFO and Scopus databases. Levels of evidence were assigned according to the
classification system of the Oxford Centre for Evidence-Based Medicine version
2009. The strength of recommendations was achieved by multiple step formalized
procedures to reach a consensus. Efficacy, risks, patient preferences and
applicability of available therapies were weighed up against each other. The
guidelines were reviewed and approved by the board of directors of the societies
engaged in the development of the guidelines. RESULTS AND CONCLUSION:
Amitriptyline and duloxetine are recommended in the case of comorbid depressive
disorders or generalized anxiety disorder and pregabalin in the case of
generalized anxiety disorder. Off-label use of duloxetine and pregabalin can be
considered if there are no comorbid mental disorders or no generalized anxiety
disorder. Strong opioids are not recommended.
PMID- 28493232
TI - Anthracycline induced cardiotoxicity: biomarkers and "Omics" technology in the
era of patient specific care.
AB - Anthracyclines are highly effective against a variety of malignancies. However,
their dose-dependent cardiotoxic effects can potentially limit their use. In the
past decade, serum biomarkers have been used to diagnose, monitor, predict, and
prognosticate disease. Biomarkers such as cardiac troponin and natriuretic
peptides have some predictive value, but still lack reliability in this patient
population. Novel biomarkers such as galectin-3, soluble ST-2 proteins,
myeloperoxidase, and fibrocytes are being explored as potential biomarkers to
reliably predict the onset of cardiotoxicity. Leveraging multiomics technology to
map highly sensitive biomarkers in an integrated approach through pattern
deconvolution may better define those at highest risk of developing
cardiotoxicity and further the goal of precision medicine. In this work, we aim
to provide a brief overview of traditional serum biomarkers, summarize current
investigations on novel circulating biomarkers, and discuss a systems-based
approach to anthracycline-induced cardiotoxicity through "omics" technology.
PMID- 28493234
TI - Exploration of Involved Key Genes and Signaling Diversity in Brain Tumors.
AB - Brain tumors are becoming a major cause of death. The classification of brain
tumors has gone through restructuring with regard to some criteria such as the
presence or absence of a specific genetic alteration in the 2016 central nervous
system World Health Organization update. Two categories of genes with a leading
role in tumorigenesis and cancer induction include tumor suppressor genes and
oncogenes; tumor suppressor genes are inactivated through a variety of mechanisms
that result in their loss of function. As for the oncogenes, overexpression and
amplification are the most common mechanisms of alteration. Important cell cycle
genes such as p53, ATM, cyclin D2, and Rb have shown altered expression patterns
in different brain tumors such as meningioma and astrocytoma. Some genes in
signaling pathways have a role in brain tumorigenesis. These pathways include
hedgehog, EGFR, Notch, hippo, MAPK, PI3K/Akt, and WNT signaling. It has been
shown that telomere length in some brain tumor samples is shortened compared to
that in normal cells. As the shortening of telomere length triggers chromosome
instability early in brain tumors, it could lead to initiation of cancer. On the
other hand, telomerase activity was positive in some brain tumors. It is
suggestive that telomere length and telomerase activity are important diagnostic
markers in brain tumors. This review focuses on brain tumors with regard to the
status of oncogenes, tumor suppressors, cell cycle genes, and genes in signaling
pathways as well as the role of telomere length and telomerase in brain tumors.
PMID- 28493233
TI - Neurite Outgrowth Stimulated by Oxytocin Is Modulated by Inhibition of the
Calcium Voltage-Gated Channels.
AB - Neuropeptide oxytocin contributes to the regulation of the neuron differentiation
and cell morphology. However, the precise mechanisms are not yet fully
understood. Oxytocin receptor function and its coupling to calcium entry are
obvious objects of interest in relation to the neuron morphology. Postsynaptic
scaffolding proteins including SHANK proteins interact with other synaptic
molecules and change dendritic morphology. SH-SY5Y neuroblastoma cell line
represents a useful neurobiological in vitro model to study the short-term
oxytocin effects on neurite outgrowth and underlying mechanisms. In the present
study, we show that oxytocin induces an increase in the intracellular calcium in
SH-SY5Y cells. Specificity of the calcium influx was verified by blockade of the
oxytocin receptors with oxytocin receptor antagonist L-371,257. Neurite outgrowth
stimulated by oxytocin was inhibited by specific voltage-gated calcium channel
blockers. The exposure of SH-SY5Y cells to oxytocin resulted in a significant
increase in the gene expression of SHANK1 and SHANK3 proteins. Overall, the
present data indicate that oxytocin may contribute to the regulation of
scaffolding proteins expression known to be associated with clusters of calcium
channels at the cell membrane. It appears that oxytocin stimulated neurite
outgrowth is, at least, in part dependent on the voltage-gated calcium channels.
PMID- 28493235
TI - The Impact of Radiation and Its Timing on Donor Internal Mammary Vessel
Histopathology at the Time of Autologous Microvascular Breast Reconstruction.
PMID- 28493236
TI - Donor-Site Outcomes for the Osteocutaneous Radial Forearm Free Flap.
PMID- 28493237
TI - Dedicated Barrett's surveillance sessions managed by trained endoscopists improve
dysplasia detection rate.
PMID- 28493238
TI - Cold polypectomy for duodenal adenomas: a prospective clinical trial.
AB - Background and study aims Endoscopic resection is effective in treating
nonampullary duodenal adenomas but has a high incidence of complications. Cold
polypectomy, including cold forceps polypectomy (CFP) and cold snare polypectomy
(CSP), is safe and effective in treating colorectal polyps. However, its utility
in sporadic nonampullary duodenal adenomas has not been investigated. The purpose
of this prospective study was to examine the safety and efficacy of cold
polypectomy for sporadic nonampullary duodenal adenomas. Patients and methods
Between March 2015 and June 2016, patients who were endoscopically diagnosed with
sporadic nonampullary duodenal adenomas up to 6 mm underwent cold polypectomy.
Patients with pathologically confirmed adenomas underwent endoscopic biopsy 3
months after resection. The main outcomes of interest were incomplete resection
and complications. Results Overall, 39 lesions in 30 patients were removed via
cold polypectomy (CFP, 9 lesions in 8 patients; CSP, 30 lesions in 22 patients).
Seven of 9 (77.8 %) and 29 of 30 (96.7 %) lesions were removed en bloc via CFP
and CSP, respectively. Pathologically, 34 of the 39 lesions (87.2 %) were
confirmed as adenomas, and their mean size was 3.9 +/- 1.2 mm (range 2 - 6 mm).
Of the 34 adenomas, 20 (58.8 %) were R0 resection lesions, of which 3 of 9 (33.3
%) and 17 of 25 (68.0 %) had undergone CFP and CSP, respectively. No delayed
bleeding or intraprocedural/delayed perforation was observed. All 30 patients
with the 34 pathologically confirmed adenomas underwent upper gastrointestinal
endoscopy 3 months after cold polypectomy, and no morphological or pathological
recurrence was identified. Conclusions In this small study, cold polypectomy
appeared to be safe and effective in treating diminutive and small sporadic
nonampullary duodenal adenomas.(Clinical trial registration number:
UMIN000016829).
PMID- 28493239
TI - Erratum: Noninvasive Ventilation in Newborns <= 1,500 g after Tracheal
Extubation: Randomized Clinical Trial.
PMID- 28493240
TI - Does Vitamin D Status Correlate with Cardiometabolic Risk Factors in Adults with
Growth Hormone Deficiency?
AB - Apart from being individually associated with cardiometabolic health, 25(OH)D and
IGF-1 interplay with a positive correlation between them, which raises questions
about the role of vitamin D for the adverse cardiovascular (CV) risk profile in
hyposomatotropism. Thus, we aimed to investigate vitamin D status in GH
deficiency (GHD) and the association between 25(OH)D and metabolic syndrome
(MetS), its components, and other surrogate markers of CV risk. A total of 129
GHD adults (childhood-onset GHD, 41.9%) underwent blood testing (glucose,
insulin, lipid profile, uric acid); blood pressure, anthropometric and
bioelectrical-impedance measurements. Other CV risk markers were examined in a
subsample of the initial population - hsCRP, adiponectin, and asymmetric
dimethylarginine (n=88); carotid intima-media thickness (n=44). Total serum
25(OH)D, measured by electro-chemiluminescence binding assay, was used for
vitamin D status assessment (adequate,>=30 ng/ml; insufficient, 20-29.9 ng/ml;
deficient,<20 ng/ml). Data demonstrated high prevalence of hypovitaminosis D in
GHD (deficiency 79.1%; insufficiency 14.7%), with lower 25(OH)D among adult-onset
GHD subjects (14.0+/-7.2 vs. 16.8+/-8.0 ng/ml, p=0.039) and patients with MetS
(11.8+/-4.5 vs. 16.3+/-8.1 ng/ml, p<0.0001). 25(OH)D correlated negatively and
weakly with BMI, waist circumference, percent body fat, visceral fat area, and
systolic BP. Regardless of whether vitamin D is a cause or a consequence of these
metabolic abnormalities, 25(OH)D testing in hyposomatotropism is advisable.
Normalization of vitamin D status is not proven to improve CV outcomes in general
population, but it might have favorable effects in GHD, as its benefits might be
restricted to patients with both low 25(OH)D and certain risk factors.
PMID- 28493241
TI - [The Use of Jumbo Cups in Revision Total Hip Arthroplasty].
AB - Extra-large uncemented jumbo cups are among the most common methods of acetabular
revision. Jumbo cups do not contribute to bone stock restoration, and in the case
of a subsequent revision, an even larger bone defect is to be expected. Thus,
understanding long-term survival is essential. The present article discusses the
literature relevant to this topic and addresses technical and implant-specific
characteristics of jumbo cups. In summary, jumbo cups show an acceptable long
term survival rate, with aseptic loosening as the most common reason for revision
and dislocation being the most common complication. Through the development of
alternative revision systems, jumbo cups have lost their importance in today's
practice. However, they can serve as a benchmark for studies of newer
technologies in revision total hip arthroplasty.
PMID- 28493242
TI - [Current Status of Spine Surgery in Germany: Results of a Survey of Members of
the German Spine Society].
AB - Background Mono- (MSS) and bisegmental spinal fusion (BSS) are frequently
performed surgical interventions in German hospitals. Despite the high number of
cases, only few data on treatment procedures and concepts for pre-, peri-, and
postoperative care are available. The aim of the survey was to gain detailed
insights into treatment procedures and medical approaches in elective MSS and BSS
care in Germany in order to extract recommendations for improving patient care.
Materials and Methods Members of the German Spine Society (DWG) were sent a
newsletter, inviting them to participate in a survey; 209 senior physicians
agreed to do so. They were asked about length of stay (LOS), care concepts and
outcome measurement. Results The data from 142 completed questionnaires were used
in the analysis. In some aspects, there was a consistency in practice:
preoperative patient information about the care process and discharge on the
basis of qualitative criteria. However, there was also considerable variability
in practice: in rehabilitation, restrictions, radiological control, pre- and
postoperative outcome measurement and interdisciplinary coordination. Conclusion
More than half of the surveyed physicians declared that they followed a
structured care plan. However, the treatment procedures in MSS and BSS care are
very heterogeneous in German hospitals. It also became clear that this is
particularly pronounced in aspects of treatment for which evidence is lacking.
The results give important indications regarding aspects of treatment procedures
and organizational structures that can be optimized for better patient care.
PMID- 28493243
TI - [Bridges from Psychosomatics to General Practice and Family Medicine].
PMID- 28493244
TI - [German Translation of the COPD Self-Efficacy Scale: Development and Validation
of a Short Form].
AB - Illness-specific self-efficacy is important in the disease-management of patients
with COPD (Chronic Obstructive Pulmonary Disease). Nevertheless, there is no
instrument to measure the illness-specific self-efficacy in the German speaking
countries. The purposes of the study were to translate the COPD Self-Efficacy
Scale (CSES) into German (CSES-D) and to determine the psychometric criteria.
Another objective was to construct a short form of the CSES-D. A total of 199
participants with COPD were recruited. The factorial structure of the CSES
including 5 dimensions could not be confirmed with exploratory and confirmatory
factor analyses. However, the short form of the CSES-D indicated acceptable fit
indices. The internal consistencies of the subscales psychological stress
(alpha=0.95) and physical exertion (alpha=0.92) were good. The correlations
between the CSES-Dkurz and convergent and discriminant questionnaires confirmed
the validity of the instrument. The results indicate that the CSES-Dkurz is a
valid and reliable instrument to assess illness-specific self-efficacy of COPD
patients. Further, studies are needed to verify the factorial construct validity
of the CSES-Dkurz.
PMID- 28493245
TI - [The Prognostic Significance of ICF Data with Regard to Realization of
Recommendations Given in the Medical Discharge Report after In-Patient
Psychosomatic Rehabilitation].
AB - Target In this trial, the prognostic significance of ICF-related diagnostics
compared to social and medical, disease-related and personal factors with regard
to realization of recommendations given in the medical discharge report after the
in-patient psychosomatic rehabilitation should be examined. Methodology ICF
related, social and medical, disease-related and personal prognostic factors were
surveyed by questionnaires and interviews, on admission, discharge and 6 months
after discharge from rehabilitation (time of catamnesis). As target criteria,
realizations of recommendations from the fields of sports and exercise,
psychotherapy and social medicine were chosen, they could be evaluated by
telephone from N=344 participants at the time of catamnesis. For determination of
relevant predictors, bivariate and multi-variate analyses were performed. Results
70% of patients realized the recommended sports and exercise, 45% the recommended
psychotherapy and 44% a social and medical recommendation. With regard to the
target criterion for the realization of recommended sports and exercise, the
elevated prognostic factors had only a low prognostic value. For the prognosis of
the target criterion of realizing a recommended psychotherapy, interpersonal
problems and a low ability to interact in groups (Mini-ICF-APP) turned out to be
relevant ICF-related predictors. Different problems (e. g., job-related
conditions) appeared as relevant, ICF-related predictors concerning the
realization of social and medical recommendations. Disturbances of reliability,
self-evaluated by means of ICF AT-50 Psych, showed in the bivariate analyses
significant correlations with the target criteria. Conclusion Besides other
variables, also ICF-supported attributes turned out to be suitable for the
prognosis of target criteria. They should be evaluated and considered in the
rehabilitation process.
PMID- 28493246
TI - [Posttraumatic Growth after Profession-Related Traumatization in Rescue Workers].
AB - This study aims to explore the association between self-reported secondary
traumatization and personal growth in a sample of Belarusians rescue workers,
focusing on the mediating role of 2 socio-interpersonal processes (disclosure and
co-rumination). In a cross-sectional survey, self-reported posttraumatic growth
and secondary traumatization were assessed in a sample of 168 rescue workers.
Posttraumatic growth was positively linked to the extent of secondary
traumatization, likewise disclosure and co-rumination were positively linked to
posttraumatic growth. Mediation analyses revealed that the association between
secondary traumatization and posttraumatic personal growth was mediated by
disclosure and co-rumination. The results thus are in favor of a socio
interpersonal perspective on posttraumatic adjustment.
PMID- 28493247
TI - [The Systemic and the Subjective Perspective on Schizophrenia or how far Away are
we from a Patient Centred Psychiatry?]
PMID- 28493248
TI - [Editor's Comment].
PMID- 28493249
TI - ?
PMID- 28493250
TI - ?
PMID- 28493251
TI - ?
PMID- 28493252
TI - [Immunotherapy Against Head and Neck Cancer Stem Cells].
AB - Immunotherapy against head and neck cancer stem cells Immunologic therapies like
antibodies in solid tumors like squamous cell cancer of the head and neck are
administered either alone or in combination with radiation and chemotherapy.
Despite some respectable successes, the effect of this therapy reaches its limits
due the ability of the tumor to escape the immune system. Cancer stem cells seem
to play an important role in this process due to their intrinsic resistance to
conventional therapy and the ability to regenerate tumor heterogeneity. This way
they substantially contribute to the formation of recurrences and metastases.
Therefore, future immunotherapies should target specifically this subpopulation,
possibly in combination with other therapeutic modalities. In this review the
immunologic features of cancer stem cells and their potential as target for
immunotherapies is summarized.
PMID- 28493253
TI - ?
PMID- 28493255
TI - ?
PMID- 28493254
TI - [Hearing Aid Fitting in Adults].
AB - The identification and treatment of hearing disorders belong to the fundamental
tasks of an ENT-specialist. In this context the fitting of hearing aids has a
special relevance. To verify a highly qualified medical care the knowledge of the
audiological threshold values for the indication of the fitting of hearing aids
and the detection of early signs for impaired communication are essential. The
current quality assurance agreement defines technical and steric conditions
pertaining to hearing aid fitting in the context of statutory health insurance.
Only after approval of these postulated requirements the attending physician is
allowed to bring to account his effort. The current regulations on medical
devices specify both the basic requirement for a medical prescription and the
expenses for hearing aids that are covered by the healthy insurances. A qualified
hearing aid fitting is only possible if the ENT-specialist not only prescribes
the device, but also conscientiously checks the comparative adjustments made by
the hearing aid acoustician. Beside the knowledge about the general mode of
operation and the different types of hearing aids ENT-specialist should know
audiological and anatomic limits for the fitting of hearing aids.
PMID- 28493256
TI - ?
PMID- 28493257
TI - Expression of p53 and selected proliferative markers (Ki-67, MCM3, PCNA, and
topoisomerase IIalpha) in borderline ovarian tumors: Correlation with
clinicopathological features.
AB - BACKGROUND: The expression of p53 has been studied not only in primary human
ovarian carcinomas, but also in borderline ovarian tumors, however, the results
were discordant. Expression patterns of proteins involved in cell proliferation
and apoptosis have been investigated in various human neoplasms, including female
genital tract neoplasms. OBJECTIVE: The aim of this investigation was to assess
the staining pattern and immunolocalization of p53 and selected proliferative
markers (Ki-67, MCM3, PCNA, and topoisomerase IIalpha) in borderline ovarian
tumors (BOTs). DESIGN: The study group consisted of 42 women who underwent pelvic
surgery between 2006-2015. The median patients' age was 46 years. The
immunoperoxidase technique was employed using antibodies against p53, Ki-67,
MCM3, PCNA, and topoisomerase IIalpha. RESULTS: For p53, nuclear expression was
observed in BOTs, however, cytoplasmatic immunoreactivity was also detected.
Altogether, 25 (60%) tumors demonstrated positive p53 immunostaining, including
overexpression found in 6 (14%). There were no significant differences in p53
expression between subgroups of clinicopathological variables. Immunoexpression
of Ki-67, MCM3, PCNA, and topoisomerase IIalpha was nuclear. Ki-67 expression was
positive in 12 (29%) cases and there was a trend towards a relationship between
patients' age and Ki-67 staining (P=0.08). Interestingly, a significantly higher
Ki-67 expression was found in tumors of >=10 cm in diameter compared to smaller
tumors (P=0.008). MCM3 expression was detected in 38 (90%) tumors, and PCNA
expression in 28 (67%), yet none of clinicopathological factors was related to
them. Topoisomerase IIalpha expression was present in 14 (33%) cases and,
interestingly, its significantly higher expression was observed in BOTs of >=10
cm in diameter compared to smaller tumors (P=0.008). Moreover, Spearman's
correlation revealed highly significant positive associations between Ki-67 and
topoisomerase IIalpha (R=0.403, P=0.008) and Ki-67 and MCM3 (R=0.469, P=0.001).
CONCLUSIONS: We report a high positive immunostaining rate for p53, suggesting a
role of TP53 alterations in the development of BOTs in humans. The new finding of
higher topoisomerase IIalpha immunostaining positivity in BOTs of >=10 cm may be
clinically relevant and requires further studies on larger patient groups.
PMID- 28493258
TI - A regional framework for action on substance use and public health.
PMID- 28493259
TI - Situational analysis: regional review of the substance use Atlas 2015.
AB - The Atlas project on substance use is a global WHO project that aims to collect
and disseminate data on resources for the prevention and treatment of substance
use disorders. Information on resources available in the WHO Eastern
Mediterranean Region was first published in 2012. The Atlas questionnaire was
updated in 2014 and data were collected in all WHO Member States. All countries
of the Region submitted the Atlas questionnaire. This report presents the latest
key information on resources for the prevention and treatment of substance use
disorders in the Eastern Mediterranean Region based on the responses of the
countries to the questionnaire. Current estimates show that the burden
attributable to drug use disorders in the Region is high. Health system resources
for the prevention and treatment of substance use disorders vary across
countries, but are generally still insufficient to provide adequate care and
treatment for people with these disorders. Countries need to strengthen
prevention and treatment of substance use disorders, particularly by increasing
coverage of treatment interventions.
PMID- 28493260
TI - International drug control system and the United Nations General Assembly Special
Session (UNGASS) on the world drug problem: an overview.
AB - The international drug control system is one of the oldest consensus-based
multilateral systems in existence. It provides the basis for the international
community and the individual Member States to effectively put in place the
mechanisms to address the problem of drug production trafficking and use of
illicit substances at different levels. Currently, the international drug control
conventions enjoy near universal adherence, with over 180 states party to the
three international drug control conventions. This level of consensus is
impressive given the highly contentious nature of the subject matter. Since the
global drug situation remains very dynamic, the multilateral system has the
ability to adjust and respond to the changing situation over the years. This
report summarizes for healthcare managers those developments and their
implications post UNGASS for the development of policies and in identifying the
challenges and priorities for their responses to address the drug situation in
order to achieve the targets set for 2019 and the 2030 agenda for sustainable
development.
PMID- 28493261
TI - Out-of-pocket cost of drug abuse consequences: results from Iranian National
Mental Health Survey.
AB - Drug abuse has significant cost to the individual, the family and the society.
This study aimed to assess out of-pocket costs of consequences of drug use
disorder. Data were drawn from the Iranian Mental Health Survey (IranMHS) through
face-to-face interviews with 7841 respondents aged 15-64 years. We used a bottom
up cost-ofillness method for economic analysis. Out-of-pocket costs for treatment
of mental and drug problems, treatment of medical illnesses, as well as costs of
crimes were assessed. The average of total annual expense was US$ 2120.6 for
those with drug use disorder, which was 23.5% of annual income of an average
Iranian family in the year 2011. The average of total out-of-pocket cost was US$
674.6 for those with other mental disorder and US$ 421.9 for those with no mental
disorder. Catastrophic payment was reported in 47.6% of the patients with drug
use disorder and 14.4% of those with other mental disorder. Thus, considerable
amount of family resources are spent on the consequences of drug use.
PMID- 28493262
TI - Level of khat dependence, use patterns, and psychosocial correlates in Yemen: a
cross-sectional investigation.
AB - Chronic khat use is associated with negative health consequences. However, no
study has fully characterized individuals who are khat dependent. This paper
examines socio-demographic and psychosocial correlates of adult khat dependence.
A total of 270 khat users (129 women) in Yemen completed face-to-face interviews
and provided demographic information and data on patterns of khat use, subjective
mood, and sleep quality. The Severity of Dependence Scale-Khat (SDS-khat) was
used to assess level of khat dependence. A series of analysis of variance was
conducted. Khat users, on average, used khat for 5.2 hours a day (SD = 2.3) for
5.7 days a week (SD = 2.0). Individuals who screened positive for khat dependence
reported longer duration of khat sessions per day, higher frequency of khat use
per week, greater levels of negative mood and sleep disturbances, and were more
likely to endorse physical symptoms after khat use (P < 0.05). Future research
should elucidate mechanisms responsible for khat dependence symptomatology.
PMID- 28493263
TI - Pattern of addiction and its relapse among habitual drug abusers in Lahore,
Pakistan.
AB - This study assessed the pattern of drug abuse and the reasons for relapse of
addiction among male drug addicts seeking rehabilitative services in different
centres in Lahore, Pakistan. A cross-sectional survey was conducted on male drug
abusers from April to December 2016. Nonprobability purposive sampling was done
to collect a sample of 119 participants. A structured questionnaire and in-depth
interviews were used for data collection. Out of 119 participants, 71.4% were in
the age group 15-35 years. Educational levels were low in the majority, with
68.1% below secondary education. Unmarried (51.3%) and unemployed (44.5%)
participants were at the greatest risk of using drugs. The age of addiction in
45% of patients was < 18 years and 40% had been abusing substances for > 5 years.
Reasons for starting drug abuse were recreation (37%), curiosity (34.5%), and
lifechanging events (14.3%). Reasons for relapse included association with former
addicts, negative reactions from family, inability to manage the craving and
work/social stress.
PMID- 28493264
TI - Drop-out from a drug treatment clinic and associated reasons.
AB - The aim of this study was to assess drop-out rates and associated reasons among
patients at the Iranian National Center for Addiction Studies (INCAS) clinic. In
a one-year period (April 2014 to March 2015), all patients with drug dependence
who had been referred for treatment and attended for a first assessment were
included in this study (N=242). Those who received treatment were followed until
March 2016. Survival analysis showed that 70.2% had dropped out from treatment.
Log rank test showed that treatment drop-out rates differed between the different
approaches used (P < 0.001), with the lowest slope inbuprenorphine maintenance
treatment and the highest in the detoxification programme. Drop-out rates within
the first three months was 62% (SE= 0.05) and 82.4% (SE=0.03) for opioids and
stimulants dependence, respectively. Analyses were performed using SPSS (Version
21.0) and STATA software, (version 13.0). From the patients' perspective,
motivational inconsistencies were considered as the main reason for not starting
or leaving treatment. The findings of this study could give service providers a
better grasp of drop-out rates and the associated reasons.
PMID- 28493265
TI - National Rehabilitation Center programme performance measures in the United Arab
Emirates, 2013.
AB - The aim of this study was to measure the performance of the National
Rehabilitation Center (NRC) programme and the services it provides. A 6-point
tool was developed based on international standards with appropriate performance
measures. The elements of the tool were applied to the electronic data files for
2013. The results showed that there were some operational, quality and data
system issues. Some items were easily accessible, e.g. capacity, waiting time,
family involvement. Others were difficult to sort and find and some were not
available in the electronic system and had to be retrieved from other sources,
e.g. programme effectiveness. There was a high no-show rate for appointments
(46%) and readmission rate (52%) and most families did not attend family sessions
(72%). This was a valuable exercise which identified gaps in operations and
records. The findings were shared with the different teams to help improve the
quality of data and services and the tool will be used for annual performance
evaluations.
PMID- 28493266
TI - Prevalence, determinants and impacts of khat chewing among professional drivers
in Southwestern Saudi Arabia.
AB - The objective of this study was to assess the prevalence and determinants of khat
chewing, and explore its social, economic and work impacts and examine its
relation with road traffic accidents (RTA) among professional drivers in Jazan
region, Saudi Arabia. A cross-sectional study was conducted on 215 drivers
recruited from transport stations in Jazan region by random cluster sampling. An
interview questionnaire was utilized for data collection, and 47.4% of drivers
were currently khat chewers. Using a logistic regression, the independent
predictors of khat chewing were being a citizen of Saudi Arabia, divorced or
widowed, working for less than 4 hours/day, and a non-seatbelt user. Khat chewing
was significantly associated with shorter working hours; higher average number of
significant RTA, and higher frequency of traffic violation. In conclusion, khat
chewing habit affected almost half of the professional drivers in Jazan area.
Moreover, khat chewing was associated with impaired working ability and
productivity, family conflicts, and violation of traffic rules.
PMID- 28493267
TI - Substance use prevention: evidence-based intervention.
AB - The global substance use problem is a serious public health concern that affects
not only health, safety and well-being of communities, but also social and
economic development. It particularly affects children, young people and their
families. All Member States should set substance use prevention measures and
programmes as a priority in order to promote health and reduce social harm.
During the past few decades there has been a significant advance in prevention
science that has led to the development of international prevention standards and
globally accepted evidence-based interventions. This review looks into the key
requirements, components and strategic interventions needed for a public health
approach to prevention of substance use and disorders, and its health and social
consequences. It aims at supporting Member States and civil society to identify
the key elements that support countries and local communities to increase the
number of substance use protective approaches in relation to risk factors across
all relevant domains.
PMID- 28493268
TI - Development of services for substance use problems: need for a system-based
approach.
AB - This review describes systems-level innovations that may enhance accessibility,
economy and integration of treatment services for substance-related disorders.
After introducing a conceptual model to describe the resources, qualities and
effectiveness of drug treatment services, evidence is reviewed in three areas
(primary care, criminal justice, and mental health) that illustrate how systems
level concepts can be used to organize services to maximize their population
impact. Special attention is given to systems issues in relation to the
development of services in countries of the Eastern Mediterranean Region.
PMID- 28493269
TI - Interventions for the management of substance use disorders: an overview.
AB - For the past 50 years, there has been a systematic effort to expand and improve
treatment services for individuals with substance use disorders by developing an
evidence base to guide practice. This policy brief aims to review the available
interventions for the management of substance use disorders, examine the evidence
base for these interventions, including the WHO Mental Health Gap Action
Programme intervention guide, and make recommendations related to the treatment
of substance use disorders. In the development of this policy brief, numerous
documents were reviewed. The WHO Mental Health Gap Action Programme intervention
guide offers the most well synthesized summary of interventions that have
evidence of support, clinical acceptance, extensive implementation and expert
consensus. The recommendations within this policy brief incorporate the core
recommendations on substance use disorder elements included in the mhGAP
intervention guide.
PMID- 28493270
TI - Public health alternatives to incarceration for drug offenders.
AB - Drug users are vastly overrepresented in prison populations. Once inside they
face increased risks of acquiring infections such as HIV, hepatitis and TB, and
on release they face an elevated risk of fatal overdose. Relapse and recidivism
are the norm following release from prison. The implementation of evidence-based
drug treatment programmes in prison is rare, yet drug treatment in prison reduces
the transmission of infections, recidivism and fatal overdose on release.
Recognising the negative returns associated with incarceration, many
jurisdictions have begun to consider alternatives such as depenalisation of the
personal use of illicit drugs, provision of treatment and social reintegration of
drug offenders, and a shift in focus from supply reduction to demand and harm
reduction measures in the community and in prison. Women with drug problems are
twice as likely to have been imprisoned for a drug offence as incarcerated men.
Similarly, HIV prevalence is higher among female inmates. Serious attention
should be paid to implementation of non-custodial sentences for women,
particularly during pregnancy and those with young children.
PMID- 28493271
TI - Alcohol and substance use in humanitarian and postconflict situations.
AB - A wide range of substance use problems are prevalent in a variety of humanitarian
settings. The Inter Agency Standing Committee (IASC) guidelines on mental health
and psychosocial support during emergencies highlights that during humanitarian
and post conflict situations, substance use is associated with problems including
gender-based violence, organized crime and the serious neglect of children.
Although substance use is a public health issue in humanitarian settings it has
always been a neglected area of public health with very limited information
available in both published and grey literature on this matter. This review
presents an overview of the problem and existing assessment and interventions
tools to address substance use in conflict and post-conflict situations.
PMID- 28493272
TI - Khat use and related addiction, mental health and physical disorders: the need to
address a growing risk.
AB - Khat use is a drug problem characteristic of the Eastern Mediterranean Region,
which is a widespread culturally accepted practice in some countries and is
becoming more prevalent in others. Although limited use may not be accompanied by
serious consequences, prolonged exposure could lead to dependence, psychosis and
other psychiatric disorders and physical conditions such as hypertension,
cardiovascular complications, sexual dysfunction, hepatoxicity and reduced birth
weight of infants born to khat-chewing mothers. The widespread use and its burden
on health and economy has raised concerns in the Region, although the extent of
the problem is not well assessed. Additionally, most countries do not have a
clear policy and plan with regard to khat use, and therefore there is hardly any
structured prevention and treatment plan in place to respond to the problem. This
review presents a picture of the extent of the problem, elaborates on related
existing research initiatives and international treaties, policies and health
service provisions, and outlines best policy and programme interventions in khat
use countries.
PMID- 28493273
TI - Use of amphetamine-type stimulants in the Islamic Republic of Iran, 2004-2015: a
review.
AB - Amphetamine-type stimulants (ATS) are the second most commonly used illicit drugs
in the world, after cannabis. The production of ATS has increased worldwide,
including in the Middle East. This review aims to assess ATS use in the Islamic
Republic of Iran. PubMed, Scientific Information Database (a national database)
and Iranian Center for Addiction Studies were searched. The review included
studies on the general population, university and high school students, other
specific populations, and drug users. The result show that self-reported
methamphetamine and ecstasy use in 2016 was < 1% in the general population and
university and high-school students, but the prevalence was higher in certain
groups. There has also been an increase in the proportion of ATS users among
clients of drug treatment centres. The findings highlight the need for high
quality epidemiological studies and closer monitoring of stimulant use in
different populations.
PMID- 28493274
TI - Developing an interministerial substance use response strategy for Lebanon:
process, content and lessons learned.
AB - Evidence on substance use in Lebanon shows an increase in usage, limited
availability and accessibility to evidence-based services, and high level of
stigma and discrimination. In line with the "Mental Health and Substance Use
Strategy for Lebanon 2015-2020", the Ministry of Public Health initiated the
process of developing a strategy focused on substance use response to address
these challenges in collaboration with the Ministries of Education and Higher
Education, Interior and Municipalities, Justice and Social Affairs. The result of
this process was a strategy launched jointly by the ministries including six
domains of action covering the whole spectrum of substance use response with
strategic objectives addressing the challenges identified through stakeholders'
consultations. The following key principles adopted throughout the process
contributed to the successful development of the strategy: building on evidence
and international frameworks, maximizing the participation of all stakeholders,
prioritising national consensus, maintaining flexibility and maximizing
transparency.
PMID- 28493275
TI - Focus issue | Bioartificial organs and tissue engineering.
PMID- 28493276
TI - Analytical Characterization of the Hydrolysis of Barley Malt Macromolecules
During Enzymatic Degradation Over Time Using AF4/MALS/RI.
AB - The changes on the molecular weight distribution (MWD) and particle size
distribution (PSD) during hydrolysis of barley malt in isothermal mashing
procedures were determined using asymmetrical flow field flow fractionation
coupled to multiangle laser light scattering and refractive index (AF4/MALS/RI).
Mash/trials were focused on amylolytic starch degradation. Therefore,
temperatures (65, 70, and 75 degrees C) were selected according to alpha- and
beta-amylases range of activity. Samples were produced by triplicate, tracking
amylolytic processes over time periods from 10 to 90 min in each mash/trial.
AF4/MALS/RI analysis demonstrated significant differences on the values of the
MWD and PSD according to the temperature/time profile used. At mashing times over
30 min at a temperature of 65 degrees C, when alpha- and beta-amylase are both
active, the decrease over time of the MWD and PSD was significantly higher (P <
0.005) than at 70 degrees C when mainly alpha-amylase is active. At 75 degrees
C, also the activity of alpha-amylase decreased and the MWD and PSD were
significantly lower (P < 0.005) than at 70 or 65 degrees C at any time of the
procedure. The MWD and PSD of beer components influence beer palate fullness,
thus AF4/ MALS/RI would be a powerful tool for breweries to adapt their
technological processes to obtain beers with particular sensorial attributes.
PMID- 28493277
TI - Bone mineral density in complete androgen insensitivity syndrome and the timing
of gonadectomy.
AB - OBJECTIVE: Low bone mineral density (BMD) has been reported in complete androgen
insensitivity syndrome (CAIS), but the impact of timing of gonadectomy is not
known. We aimed to assess the relationship between age of gonadectomy and BMD in
women with CAIS. DESIGN: Retrospective analysis of pre- and post-gonadectomy
parameters in women with CAIS attending an adult Disorders of Sex Development
(DSD) clinic in a tertiary centre. PATIENTS: One hundred and thirteen women with
CAIS. MEASUREMENTS: Dual-energy X-ray absorptiometry (DXA) before and after
gonadectomy; and pre-gonadectomy hormone profile. RESULTS: Mean BMD was reduced
(95% confidence interval); T-score -1.34 (-1.55 to -1.13; P<.001) at the lumbar
spine and -0.3 (-0.49 to -0.12; P=.001) at the hip. There was no relationship
between age of gonadectomy and BMD. Thirty-two subjects had BMD measured before
or within 2 years of gonadectomy, and mean BMD was reduced (95% CI) at the lumbar
spine; T-score: -1.05 (-1.54 to -0.57; P<.001), but was normal at the hip; T
score -0.04 (-0.35 to 0.28; P=.8). There was no relationship between BMD and
history of hernia, testosterone, oestradiol or follicle stimulating hormone
levels. Twelve subjects had DXA both before and after gonadectomy, and after 4.3
(1.7-12.8) years, there was no change in BMD. CONCLUSIONS: We found reduced BMD
at the spine and hip in subjects with CAIS. We found no relationship between age
of gonadectomy and BMD, and we also found no drop in BMD in subjects followed up
after gonadectomy.
PMID- 28493278
TI - The bicellular tensile force sorts the localization of LSRs in bicellular and
tricellular junctions.
AB - Lipolysis-stimulated lipoprotein receptors (LSRs) localize to tricellular tight
junctions. Recent studies have shown that changes in the localization and
expression profiles of LSRs are associated with malignancy of endometrial
carcinomas, although the precise mechanisms by which malignant progression
induces changes in the localization of LSRs are still unknown. In this study, we
found that changes in cell tension correlated with alterations in the junctional
localization of LSRs in endometrial cancer Sawano cells. At high cell densities,
myosin phosphatase target subunit 1 (MYPT1) localized to bicellular junctions,
whereas activated myosin regulatory light chain 2 (MRLC2) was dislocated from
these regions, suggesting that circumferential tensile forces decreased at high
cell densities. Under these conditions, LSRs localized to tricellular junctions.
In contrast, a phosphorylated form of MRLC2 localized to bicellular regions,
while MYPT1 was excluded from these regions, suggesting that tensile forces
formed along the circumferential edge at low cell densities. It is noteworthy
that, when cells were cultured under these conditions, LSRs localized to
bicellular regions. Upon treatment with a myosin inhibitor, LSR localization in
bicellular junctions decreased at low cell densities. Overall, our results
indicate that the modulation of cellular tension was involved in the
translocation of LSRs from bicellular to tricellular tight junctions.
PMID- 28493279
TI - Specific detection of GII-1 lineage of infectious bronchitis virus.
AB - : Infectious bronchitis virus (IBV) is a worldwide prevalent RNA virus that
causes highly contagious and economically devastating disease in chicken. The
virus exists in many different genetic forms which made the disease control very
difficult. The present study describes the development and validation of TaqMan
probe-based real-time reverse transcription-polymerase chain reaction (real-time
RT-PCR) targeting the S1 coding region of S gene characteristic for the GII-1
lineage (formerly the D1466-like variant) of IBV. These strains are quite
different from other European IBV belonging to different lineages of the GI
genotype. The developed method was 30-fold more sensitive than used so far for
standard nested RT-PCR with detection limit of 56 RNA copies per reaction. The
specificity of the assay was also evaluated with a panel of different poultry
pathogens. Repeatability and reproducibility of the method was very high with
coefficients of variation lower than 4%. One hundred and twenty-seven IBV
positive samples were tested by this method and GII-1 strains were detected in
four of them (3.15%) which indicate a decrease in the GII-1 IBV prevalence in
Poland. The assay was proven to be a valuable tool for rapid diagnosis of GII-1
lineage of IBV strains and moreover it enabled the monitoring of viral loads
which can be used to assess disease progression. SIGNIFICANCE AND IMPACT OF THE
STUDY: This study reports a TaqMan probe-based real-time reverse transcription
polymerase chain reaction (real-time RT-PCR) for rapid and accurate
identification of GII-1 lineage (formerly D1466-like variant) of infectious
bronchitis virus (IBV). The assay revealed to be more sensitive than standard
nested RT-PCR assay, previously used for this purpose. The developed assay has
been tested on numerous field samples and revealed 3.15% prevalence of this
lineage of IBV in Polish chicken population. Moreover, this new assay enables the
assessment of viral load measurement which might be useful for epidemiology and
pathogenesis studies.
PMID- 28493280
TI - Aquifers Shared Between Mexico and the United States: Management Perspectives and
Their Transboundary Nature.
AB - Totally 36 aquifers have been identified along the Mexico-U.S. border. Of these,
only 16 have adequate data to provide a reasonable level of confidence to
categorize them as transboundary. Limited and/or contrasting data over the other
aquifers in the region reflects the void in transboundary groundwater management
and assessment mechanisms throughout much of the Mexico-U.S. border. This paper
identifies management mechanisms, structures, and institutional prioritization
related to transboundary aquifers shared between Mexico and the United States. It
also evaluates the differences in the transboundary nature of these aquifers, and
how their combined hydrological and geographical considerations interrelate with
local and regional social, economic, political, and even scale dimensions to
create complex management challenges.
PMID- 28493281
TI - Editorial: Being a mental health nurse.
PMID- 28493282
TI - The importance of relationships: Care planning and care coordination in mental
health.
PMID- 28493283
TI - The Current Status of Research on the Integration of Sexual and Reproductive
Health and HIV Services.
AB - Integration of services for sexual and reproductive health (SRH) and HIV has been
widely promoted globally in the belief that both clients and health providers
benefit through improvements in quality, efficient use of resources, and lower
costs, helping to maximize limited health resources and provide comprehensive
client-centered care. This article builds on the growing body of research on
integrated sexual SRH and HIV services. It brings together critical reviews on
issues within the wider SRH and rights agenda and synthesizes recent research on
integrated services, drawing on the Integra Initiative and other major research.
Unintended pregnancy and HIV are intrinsically interrelated SRH issues, however
broadening the constellation of services, scaling up, and mainstreaming
integration continue to be challenging. Overcoming stigma, reducing gender-based
violence, and meeting key populations' SRH needs are critical. Health systems
research using SRH as the entry point for integrated services and interaction
with communities and clients is needed to realize universal health coverage.
PMID- 28493284
TI - Prognostic value of preoperative anti-thyroglobulin antibody in differentiated
thyroid cancer.
AB - CONTEXT: The coexistence of differentiated thyroid cancer (DTC) and thyroid
autoimmune disease could represent a better or worse prognosis. This study
investigated the prognostic importance of preoperative anti-thyroglobulin
antibody (TgAb) in DTC patients. DESIGN AND PATIENTS: This retrospective hospital
cohort study enrolled 1171 consecutive DTC patients with preoperative TgAb data,
who underwent total thyroidectomy between January 2006 and December 2011.
Clinical parameters studied included demographics, primary tumour
characteristics, radioiodine therapy, thyroid function tests, preoperative
thyroglobulin (Tg) and TgAb levels, and cancer persistence/recurrence. RESULTS: A
total of 254 (21.7%) patients were preoperatively TgAb positive. The percentage
positive for thyroid peroxidase (TPO) antibody and lymphocytic thyroiditis was
significantly higher in the TgAb-positive group. The TgAb-positive group had a
significantly higher rate of lymphatic invasion and lymph node metastasis both
overall and in patients without TPOAb and lymphocytic thyroiditis (non-HT group).
The mean number of total and central lymph nodes dissected and rate of lateral
lymph node dissection were significantly higher in the TgAb-positive group, both
overall and in non-HT patients. In regression analysis, preoperative TgAb was an
independent risk factor for lateral lymph node metastasis. Over 50.2+/-14.5
months of follow-up, disease persistence/recurrence was not significantly
different between patients with and without TgAb, both overall and in non-HT
patients. Preoperative TgAb showed no significant correlation with final disease
status. CONCLUSION: Positive preoperative serum TgAb is associated with worse
primary tumour characteristics but rarely showed poor prognosis, probably due to
more aggressive treatment of these subjects.
PMID- 28493285
TI - Hidden floral adaptation to nocturnal moths in an apparently bee-pollinated
flower, Adenophora triphylla var. japonica (Campanulaceae).
AB - The discrepancy between observed flower visitors and those predicted based on
floral phenotype has often cast doubt on the pollination syndrome concept. Here
we show that this paradox may be alleviated by gaining better knowledge of the
contributions of different flower visitors to pollination and the effects of
floral traits that cannot be readily perceived by humans in Adenophora triphylla
var. japonica. The blue, bell-shaped and pendant flowers of A. triphylla appear
to fit a bee pollination syndrome. In contrast to this expectation, recent
studies show that these flowers are frequented by nocturnal moths. We compared
the flower visitor fauna, their visitation frequency and their relative
contributions to seed set between day and night in two field populations of A.
triphylla in Japan. We also determined the floral traits associated with temporal
changes in the visitor assemblage, i.e. the timing of anthesis, the timing of
changes in the sexual phase and the diel pattern of nectar production. While A.
triphylla flowers were visited by both diurnal and nocturnal insects, the results
from pollination experiments demonstrate that their primary pollinators are
nocturnal settling-moths. Moreover, the flowers opened just after sunset, changed
from staminate to pistillate phase in successive evenings and produced nectar
only during the night, which all conform to the activity of nocturnal/crepuscular
moths. Our study illustrates that the tradition of stereotyping the pollinators
of a flower based on its appearance can be misleading and that it should be
improved with empirical evidence of pollination performance and sufficient trait
matching.
PMID- 28493286
TI - Comprehensive analysis of cutaneous T-cell lymphoma (CTCL) incidence and
mortality in Canada reveals changing trends and geographic clustering for this
malignancy.
AB - BACKGROUND: Previous reports of geographic clustering of cutaneous T-cell
lymphoma (CTCL) in Texas, Pittsburgh, and Sweden as well as the occurrence of
CTCL in married couples and family members raise a possibility of the existence
of an external and potentially preventable trigger(s) for this rare skin cancer.
METHODS: The authors studied CTCL incidence and mortality in Canada using 3
distinct population-based cancer databases. Data on patients' sex, age at the
time of diagnosis, subtype of CTCL malignancy, reporting province, city, and
postal code were analyzed. CTCL cases were mapped across Canada using geographic
information systems software. RESULTS: In total, 6685 patients with CTCL were
identified in Canada during 1992 through 2010 (CTCL incidence rate, 11.32 cases
per million individuals per year), of which 58% were males. The mean age at
diagnosis was 59.4 +/- 21.5 years. Geographic analysis of patients revealed
increased CTCL incidence on the provincial and city levels in several eastern
provinces and in Manitoba. An analysis according to postal codes (Forward
Sortation Area [FSA]) identified select communities in which several high
incidence FSAs were contiguous or adjacent. Several of these FSAs were located in
industrial regions of Canadian cities. Conversely, 3 of 8 low-incidence FSAs were
clustered in Ottawa, Ontario, which has very little industrial presence. An
analysis of CTCL mortality in Canada corroborated the current incidence findings.
CONCLUSIONS: The current results provide a comprehensive analysis of CTCL burden
in Canada and highlight several important areas of geographic case clustering.
These findings argue that industrial exposures may play an important role in
promoting CTCL pathogenesis. Cancer 2017;123:3550-67. (c) 2017 American Cancer
Society.
PMID- 28493287
TI - Soft tissue sarcoma nomograms and their incorporation into practice.
AB - The accurate prediction of prognosis in patients with soft tissue sarcoma (STS)
is a challenging issue. Extreme variability in the clinical and pathological
characteristics of this family of tumors hinders the simple stratification of
patients into meaningful prognostic cohorts. Precision medicine tools for the
prediction of prognosis, such as nomograms, enable personalized computation of
outcome based on clinical and pathological characteristics of both patient and
tumor. The eighth edition of the American Joint Committee on Cancer staging
manual moved from a "population-based" to a "personalized" approach endorsing
high-quality nomograms to improve clinician prediction ability in definite
patient subgroups. The first nomogram for STS was published in 2002, and this was
followed by several prognostic predictors offered to clinicians. Focusing on a
specific STS subgroup or site, nomograms can take into consideration highly
specific factors relevant only in that particular scenario, thereby maximizing
prognostic ability. The objective of this review was to critically evaluate
available nomograms for patients with STS to provide clinicians and researchers
with a choice of the most optimal tool for each specific patient. Cancer
2017;123:2802-20. (c) 2017 American Cancer Society.
PMID- 28493288
TI - Outcomes for patients with locally advanced pancreatic adenocarcinoma treated
with stereotactic body radiation therapy versus conventionally fractionated
radiation.
AB - BACKGROUND: As systemic therapy has improved for locally advanced pancreatic
cancer (LAPC), efforts to improve local control with optimal radiotherapy may be
critical. Although conventionally fractionated radiation therapy (CFRT) has more
recently shown a limited role in LAPC, stereotactic body radiation therapy (SBRT)
is an emerging approach with promising results. With no studies to date comparing
SBRT with CFRT for LAPC, this study used the National Cancer Data Base (NCDB) to
evaluate these 2 modalities. METHODS: With the NCDB, patients with American Joint
Committee on Cancer cT2-4/N0-1/M0 adenocarcinoma of the pancreas diagnosed from
2004 to 2013 were analyzed. Radiation therapy delivered at <=2 Gy was deemed
CFRT, and radiation therapy delivered at >=4 Gy per fraction was considered SBRT.
Kaplan-Meier analysis, log-rank testing, and multivariate Cox proportional
hazards regression were performed with overall survival (OS) as the primary
outcome. Propensity score matching was used. RESULTS: Among 8450 patients, 7819
(92.5%) were treated with CFRT, and 631 (7.5%) underwent SBRT. Receipt of SBRT
was associated with superior OS in the multivariate analysis (hazard ratio, 0.84;
95% confidence interval, 0.75-0.93; P < .001). With propensity score matching,
988 patients in all were matched, with 494 patients in each cohort. Within the
propensity-matched cohorts, the median OS (13.9 vs 11.6 months) and the 2-year OS
rate (21.7% vs 16.5%) were significantly higher with SBRT versus CFRT (P =
.0014). CONCLUSIONS: In this retrospective review using a large national
database, SBRT was associated with superior OS in comparison with CFRT for LAPC,
and these findings remained significant in a propensity-matched analysis. Further
prospective studies investigating these hypothesis-generating results are
warranted. Cancer 2017;123:3486-93. (c) 2017 American Cancer Society.
PMID- 28493290
TI - Circulating thyroid cancer biomarkers: Current limitations and future prospects.
AB - Differentiated thyroid cancer (DTC) is the most common malignancy of the
endocrine system. There has been a significant increase in its incidence over the
past two decades attributable mainly to the use of more sensitive diagnostic
modalities. Ultrasound-guided fine needle aspiration cytology is the mainstay of
diagnosis of benign disorders and malignancy. However, approximately 20% of
lesions cannot be adequately categorized as benign or malignant. In the
postoperative setting, monitoring of thyroglobulin (Tg) levels has been employed
for the detection of disease recurrence. Unfortunately, Tg antibodies are common
and interfere with Tg measurement in this subset of patients. Despite this
limitation, Tg remains the sole widely used thyroid cancer biomarker in the
clinical setting. In an attempt to bypass antibody interference, research has
focused mainly on mRNA targets thought to be exclusively expressed in thyroid
cells. Tg and thyroid stimulating hormone receptor (TSHR) mRNA have been
extensively studied both for discerning between benign disease and malignancy and
in postoperative disease surveillance. However, results among reports have been
inconsistent probably reflecting considerable differences in methodology.
Recently, microRNA (miRNA) targets are being investigated as potential biomarkers
in DTC. MiRNAs are more stable molecules and theoretically are not as vulnerable
as mRNA during manipulation. Initial results have been encouraging but large
scale studies are warranted to verify and elucidate their potential application
in diagnosis and postoperative surveillance of thyroid cancer. Several other
novel targets, primarily mutations and circulating cells, are currently emerging
as promising thyroid cancer circulating biomarkers. Although interesting and
intriguing, data are limited and derive from small-scale studies in specific
patient cohorts. Further research findings demonstrating their value are awaited
with anticipation.
PMID- 28493291
TI - Prevalence of primary aldosteronism among patients with type 2 diabetes.
AB - CONTEXT: Diabetes and hypertension coexist in 40%-60% of individuals with type 2
diabetes. The coexistence of these two conditions is associated with increased
risk of retinopathy, nephropathy and cardiovascular disease. OBJECTIVE: To
investigate the prevalence of primary aldosteronism (PA) in a general cohort of
persons with type 2 diabetes. DESIGN: Cross-sectional study involving six
diabetes outpatient clinics in Sweden. PATIENTS: were enrolled individuals with
type 2 diabetes between February 2008 and December 2013. MEASUREMENTS: Plasma
aldosterone concentrations (PAC pmol/L) and direct renin concentrations (DRC
mIU/L) were measured. Patients with increased aldosterone renin ratios (ARR) >65
were further evaluated for PA. RESULTS: Of 578 consecutively screened patients
with type 2 diabetes, 27 were treated with mineralocorticoid receptor antagonists
(MRA) and potassium-sparing diuretics not further evaluated. Among the remaining
551 patients, 38 had increased ARR, including 22 who were clinically indicated
for PA tests and 16 who were not further evaluated due to severe comorbidities
and old age. There were five (0.93%) patients with confirmed PA after
computerized tomography and adrenal venous sampling. Patients with PA had higher
systolic blood pressure (P=.032) and lower potassium levels (P=.027) than those
without PA. No significant association was found between plasma aldosterone and
diabetic complications. CONCLUSIONS: The prevalence of PA in an unselected cohort
of patients with type 2 diabetes is relatively low, and measures of plasma
aldosterone are not strong risk factors for micro- and macrovascular diabetic
complications.
PMID- 28493292
TI - Organocatalytic Stereoconvergent Synthesis of alpha-CF3 Amides:
Triketopiperazines and Their Heterocyclic Metamorphosis.
AB - The highly enantioselective alkylation of alpha-CF3 enolates, generated from
triketopiperazines, has been accomplished through use of a bifunctional thiourea
organocatalyst to facilitate 1,4-addition to varied enone acceptors. On treatment
with appropriate nitrogen nucleophiles, the chiral triketopiperazine products
undergo a metamorphosis, to provide novel fused heterocyclic lactams such as
extended pyrazolopyrimidines.
PMID- 28493289
TI - Intestinal epithelial claudins: expression and regulation in homeostasis and
inflammation.
AB - The intestinal epithelium forms a highly dynamic and selective barrier that
controls absorption of fluid and solutes while restricting pathogen access to
underlying tissues. Barrier properties are achieved by intercellular junctions
that include an apical tight junction (TJ) and subjacent adherens junctions and
desmosomes. The TJ tetraspan claudin proteins form pores between epithelial cells
to control paracellular fluid and ion movement. In addition to regulation of
barrier function, claudin family members control epithelial homeostasis and are
expressed in a spatiotemporal manner in the intestinal crypt-luminal axis. This
delicate balance of physiologic differential claudin protein expression is
altered during mucosal inflammation. Inflammatory mediators influence
transcriptional regulation, as well as endocytic trafficking, targeting, and
retention of claudins in the TJ. Increased expression of intestinal epithelial
claudin-1, -2, and -18 with downregulation of claudin-3, -4, -5, -7, -8, and -12
has been observed in intestinal inflammatory disorders. Such changes in claudin
proteins modify the epithelial barrier function in addition to influencing
epithelial and mucosal homeostasis. An improved understanding of the regulatory
mechanisms that control epithelial claudin proteins will provide strategies to
strengthen the epithelial barrier function and restore mucosal homeostasis in
inflammatory disorders.
PMID- 28493293
TI - Responsiveness to oral prednisolone in severe asthma is related to the degree of
eosinophilic airway inflammation.
AB - BACKGROUND: Patients with severe asthma appear relatively corticosteroid
resistant. Corticosteroid responsiveness is closely related to the degree of
eosinophilic airway inflammation. The extent to which eosinophilic airway
inflammation in severe asthma responds to treatment with systemic corticosteroids
is not clear. OBJECTIVE: To relate the physiological and inflammatory response to
systemic corticosteroids in asthma to disease severity and the baseline extent of
eosinophilic inflammation. METHODS: Patients with mild/moderate and severe asthma
were investigated before and after 2 weeks of oral prednisolone (Clintrials.gov
NCT00331058 and NCT00327197). We pooled the results from two studies with common
protocols. The US study contained two independent centres and the UK one
independent centre. The effect of oral corticosteroids on FEV1 , Pc20, airway
inflammation and serum cytokines was investigated. Baseline measurements were
compared with healthy subjects. RESULTS: Thirty-two mild/moderate asthmatics, 50
severe asthmatics and 35 healthy subjects took part. At baseline, both groups of
asthmatics had a lower FEV1 and Pc20 and increased eosinophilic inflammation
compared to healthy subjects. The severe group had a lower FEV1 and more
eosinophilic inflammation compared to mild/moderate asthmatics. Oral prednisolone
caused a similar degree of suppression of eosinophilic inflammation in all
compartments in both groups of asthmatics. There were small improvements in FEV1
and Pc20 for both mild/ moderate and severe asthmatics with a correlation between
the baseline eosinophilic inflammation and the change in FEV1 . There was a ~50%
reduction in the serum concentration of CXCL10 (IP-10), CCL22 (MDC), CCL17
(TARC), CCL-2 (MCP-1) and CCL-13 (MCP-4) in both asthma groups after oral
corticosteroids. CONCLUSIONS AND CLINICAL RELEVANCE: Disease severity does not
influence the response to systemic corticosteroids. The study does not therefore
support the concept that severe asthma is associated with corticosteroid
resistance. Only baseline eosinophilic inflammation was associated with the
physiological response to corticosteroids, confirming the importance of measuring
eosinophilic inflammation to guide corticosteroid use.
PMID- 28493294
TI - Commercial Mineral Enhanced Dairy By-Products as Sodium Replacers, Antioxidants
and Calcium Fortifiers in Sausages.
AB - Sausages are perceived as high in Na and with a too high Na:K ratio. Frankfurter
type sausages are regarded as important contributors of sodium in the diet and
thereby of health risks. Surplus products from the dairy industry are various
mineral powders enriched in either potassium, calcium, or phosphate and include
various amounts of lactose. Sausages were produced at 3 sodium levels (equivalent
to 13, 15, and 17 g NaCl/kg sausage) using 4 different milk ingredients (a dried
skimmed milk powder, a calcium enriched milk powder, a potassium enriched powder,
and a lactose enriched powder). The sausages with added calcium and potassium
enriched milk powders resulted in the hardest sausages when compared at the same
sodium level. Milk mineral addition also produced whiter and less red sausages.
No effect on rancidity after 6 wk at chill (4 degrees C) storage was observed by
adding milk minerals, when compared with adding dried skimmed milk powder. A
significant advantage of using these milk minerals in sausages is that the Na:K
ratio can be reduced from an unhealthy (in this study 36) to a far healthier
ratio ( 2) with limited or no taste changes. High additions of milk calcium (6
g/kg), where Ca-phosphates prevail, added as milk mineral, had no influence on
sensory bitterness or aftertaste as typically observed for CaCl2 additions. Ca
additions to sausages are presently presumed to be an advantage with respect to
human nutrition.
PMID- 28493297
TI - The error analysis of Lobular and segmental division of right liver by volume
measurement.
AB - The aim of this study is to explore the inconsistencies between right liver
volume as measured by imaging and the actual anatomical appearance of the right
lobe. Five healthy donated livers were studied. The liver slices were obtained
with hepatic segments multicolor-infused through the portal vein. In the slices,
the lobes were divided by two methods: radiological landmarks and real anatomical
boundaries. The areas of the right anterior lobe (RAL) and right posterior lobe
(RPL) on each slice were measured using Photoshop CS5 and AutoCAD, and the
volumes of the two lobes were calculated. There was no statistically significant
difference between the volumes of the RAL or RPL as measured by the radiological
landmarks (RL) and anatomical boundaries (AB) methods. However, the curves of the
square error value of the RAL and RPL measured using CT showed that the three
lowest points were at the cranial, intermediate, and caudal levels. The U- or V
shaped curves of the square error rate of the RAL and RPL revealed that the
lowest value is at the intermediate level and the highest at the cranial and
caudal levels. On CT images, less accurate landmarks were used to divide the RAL
and RPL at the cranial and caudal layers. The measured volumes of hepatic
segments VIII and VI would be less than their true values, and the measured
volumes of hepatic segments VII and V would be greater than their true values,
according to radiological landmarks. Clin. Anat. 30:585-590, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28493295
TI - Towards ultrasound-guided adaptive radiotherapy for cervical cancer: Evaluation
of Elekta's semiautomated uterine segmentation method on 3D ultrasound images.
AB - PURPOSE: 3D ultrasound (US) images of the uterus may be used to adapt
radiotherapy (RT) for cervical cancer patients based on changes in daily anatomy.
This requires accurate on-line segmentation of the uterus. The aim of this work
was to assess the accuracy of Elekta's "Assisted Gyne Segmentation" (AGS)
algorithm in semi-automatically segmenting the uterus on 3D transabdominal
ultrasound images by comparison with manual contours. MATERIALS & METHODS: Nine
patients receiving RT for cervical cancer were imaged with the 3D Clarity(r)
transabdominal probe at RT planning, and 1 to 7 times during treatment. Image
quality was rated from unusable (0)-excellent (3). Four experts segmented the
uterus (defined as the uterine body and cervix) manually and using AGS on images
with a ranking > 0. Pairwise analysis between manual contours was evaluated to
determine interobserver variability. The accuracy of the AGS method was assessed
by measuring its agreement with manual contours via pairwise analysis. RESULTS:
35/44 images acquired (79.5%) received a ranking > 0. For the manual contour
variation, the median [interquartile range (IQR)] distance between centroids (DC)
was 5.41 [5.0] mm, the Dice similarity coefficient (DSC) was 0.78 [0.11], the
mean surface-to-surface distance (MSSD) was 3.20 [1.8] mm, and the uniform margin
of 95% (UM95) was 4.04 [5.8] mm. There was no correlation between image quality
and manual contour agreement. AGS failed to give a result in 19.3% of cases. For
the remaining cases, the level of agreement between AGS contours and manual
contours depended on image quality. There were no significant differences between
the AGS segmentations and the manual segmentations on the images that received a
quality rating of 3. However, the AGS algorithm had significantly worse agreement
with manual contours on images with quality ratings of 1 and 2 compared with the
corresponding interobserver manual variation. The overall median [IQR] DC, DSC,
MSSD, and UM95 between AGS and manual contours was 5.48 [5.45] mm, 0.77 [0.14],
3.62 [2.7] mm, and 5.19 [8.1] mm, respectively. CONCLUSIONS: The AGS tool was
able to represent uterine shape of cervical cancer patients in agreement with
manual contouring in cases where the image quality was excellent, but not in
cases where image quality was degraded by common artifacts such as shadowing and
signal attenuation. The AGS tool should be used with caution for adaptive RT
purposes, as it is not reliable in accurately segmenting the uterus on 'good' or
'poor' quality images. The interobserver agreement between manual contours of the
uterus drawn on 3D US was consistent with results of similar studies performed on
CT and MRI images.
PMID- 28493299
TI - China's Transboundary Groundwater Cooperation in the Context of Emerging
Transboundary Aquifer Law.
AB - China shares more than 20 transboundary aquifers with its coaquifer states, but
they have not exploited their transboundary groundwater resources, and these
resources have not been governed by any international agreements. Given the close
interaction between surface water and groundwater, and the growing demands for
transboundary groundwater in China and its coaquifer states, there is increasing
necessity for these countries to undertake international cooperation on this
issue. This article overviews China's transboundary aquifers, reviews the duty to
cooperate on China's transboundary groundwater as well as the emerging
transboundary aquifer law. It concludes by providing some proposals on
international cooperation in this context, based on the two theories of
international water law-limited territorial sovereignty and common interests,
taking into account the practicability of China's cooperation with its coaquifer
states. The author suggests that China cooperates with its coaquifer states
through such means as the exchange of data and information, joint monitoring, the
conclusion of bilateral or multilateral aquifer agreements, the establishment of
joint management mechanisms, and international technical cooperation.
PMID- 28493298
TI - Organizing pneumonia as an extraintestinal manifestation of Crohn's disease in a
child.
AB - Crohn's disease (CD) is a chronic inflammatory disorder with an unknown etiology
that commonly involves the gastrointestinal tract, and bronchopulmonary
manifestations only occur in 0.4% of cases. There have not been any reports about
pulmonary involvement in pediatric CD patients. We experienced a 14-year-old boy
with Crohn's disease diagnosed with organizing pneumonia by chest CT-guided
biopsy examination. His pneumonia was intractable despite the administration of
multiple antibiotics, and steroid therapy was very effective. In pediatric
patients with CD whose lung disease does not respond to antibiotics, OP should be
considered as a possible diagnosis.
PMID- 28493300
TI - Timing of surgery for placenta previa with suspected abnormally invasive
placentation: a test of team competency?
PMID- 28493301
TI - The implementation of the Care Programme Approach for service users with a
learning disability. Building Bridges to the same Old Horizons?
AB - : WHAT IS KNOWN ON THE SUBJECT?: People with mental health problems and learning
disabilities often do not receive the care they require. The Care Programme
Approach (CPA) is meant to help with this. However, there have been many problems
in the past with the introduction of the CPA into mental health services. There
is no literature which explores what factors help or hinder the introduction of
the CPA for service users with a mental health and learning disability,
especially from the perspective of those responsible for overseeing this process.
WHAT DOES THIS ARTICLE ADD TO EXISTING KNOWLEDGE?: The implementation of the CPA
for this service user group is fragmented, and services are not working together
in partnership. The CPA is being effectively implemented for people who are
deemed to present with a risk to themselves or others. If a service user does not
present with a high risk, they are not provided care through the CPA. Service
users were not involved in the development or introduction of the policy in
practice. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Services need to work better
at engaging service users when they are developing and introducing new policies.
Rather than applying the CPA for all service users, across all services, it
should only be considered for those deemed to present with a high risk. It is
effectively implemented for these people. For those not deemed to present with a
high risk, services should consider using alternative service user led care
planning frameworks. ABSTRACT: Introduction The Care Programme Approach was
introduced in England to ensure services met the needs of people with mental
health problems and a concurrent learning disability (dual diagnosis). The CPA
implementation was patchy and services failed to work in partnership. Aim This
study aimed to explore the factors shaping the recent implementation of the CPA
for service users with a dual diagnosis. Method A single case study approach was
undertaken. Data were collected through interview (n = 26), documentary analysis
(n = 64), steering group observation (n = 3) and the Partnership Assessment Tool
(n = 26). Data were analysed using the Framework Approach. Results The CPA was
only effectively implemented for people who were deemed to present with a high
level of risk. Discussion The problems associated with implementation in the
1990s continue more recently for those with a dual diagnosis. The CPA has become
more aligned with risk management protocols than supporting individual service
user's recovery. Implications for practice Service users should be involved in
the implementation of policies which have an impact on their recovery. The CPA
should only be applied for those who present with high-risk issues, whilst
alternative user-led initiatives should be considered for other service users.
PMID- 28493302
TI - Instrumental variables estimation of exposure effects on a time-to-event endpoint
using structural cumulative survival models.
AB - The use of instrumental variables for estimating the effect of an exposure on an
outcome is popular in econometrics, and increasingly so in epidemiology. This
increasing popularity may be attributed to the natural occurrence of instrumental
variables in observational studies that incorporate elements of randomization,
either by design or by nature (e.g., random inheritance of genes). Instrumental
variables estimation of exposure effects is well established for continuous
outcomes and to some extent for binary outcomes. It is, however, largely lacking
for time-to-event outcomes because of complications due to censoring and
survivorship bias. In this article, we make a novel proposal under a class of
structural cumulative survival models which parameterize time-varying effects of
a point exposure directly on the scale of the survival function; these models are
essentially equivalent with a semi-parametric variant of the instrumental
variables additive hazards model. We propose a class of recursive instrumental
variable estimators for these exposure effects, and derive their large sample
properties along with inferential tools. We examine the performance of the
proposed method in simulation studies and illustrate it in a Mendelian
randomization study to evaluate the effect of diabetes on mortality using data
from the Health and Retirement Study. We further use the proposed method to
investigate potential benefit from breast cancer screening on subsequent breast
cancer mortality based on the HIP-study.
PMID- 28493303
TI - Comprehensive profiling of rhizome-associated alternative splicing and
alternative polyadenylation in moso bamboo (Phyllostachys edulis).
AB - Moso bamboo (Phyllostachys edulis) represents one of the fastest-spreading plants
in the world, due in part to its well-developed rhizome system. However, the post
transcriptional mechanism for the development of the rhizome system in bamboo has
not been comprehensively studied. We therefore used a combination of single
molecule long-read sequencing technology and polyadenylation site sequencing (PAS
seq) to re-annotate the bamboo genome, and identify genome-wide alternative
splicing (AS) and alternative polyadenylation (APA) in the rhizome system. In
total, 145 522 mapped full-length non-chimeric (FLNC) reads were analyzed,
resulting in the correction of 2241 mis-annotated genes and the identification of
8091 previously unannotated loci. Notably, more than 42 280 distinct splicing
isoforms were derived from 128 667 intron-containing full-length FLNC reads,
including a large number of AS events associated with rhizome systems. In
addition, we characterized 25 069 polyadenylation sites from 11 450 genes, 6311
of which have APA sites. Further analysis of intronic polyadenylation revealed
that LTR/Gypsy and LTR/Copia were two major transposable elements within the
intronic polyadenylation region. Furthermore, this study provided a quantitative
atlas of poly(A) usage. Several hundred differential poly(A) sites in the rhizome
root system were identified. Taken together, these results suggest that post
transcriptional regulation may potentially have a vital role in the underground
rhizome-root system.
PMID- 28493304
TI - CPAM type 2-derived mesenchymal stem cells: Malignancy risk study in a 14-month
old boy.
AB - INTRODUCTION: The association between congenital pulmonary airway malformations
(CPAM) and malignancy is reported in the literature. Interactions between the
tumor, immune, and mesenchymal stromal/stem cells (MSCs) have been recognized as
crucial for understanding tumorigenesis. We characterized MSCs isolated from CPAM
lesions in order to define potential malignancy risks. METHODS: CPAM II pulmonary
tissue was used for MSC expansion; a "healthy" lung section from the same child
was used as a comparator. Morphology, immunophenotype, differentiation and
immunological capacity, proliferative growth, gene signature telomerase activity,
and in vivo tumorigenicity in nude mice were evaluated. RESULTS: MSCs were
successfully isolated and propagated from CPAM tissue. CPAM-MSCs presented the
typical MSC morphology and phenotype, while exhibiting high proliferative
capacity, reaching confluence at a median time of 5 days as well as
differentiation capabilities. CPAM-MSCs at early passages were not neoplastic and
chromosomally normal, even though unbalanced chromosomal rearrangements were
noted by molecular karyotype. CONCLUSIONS: CPAM-MSCs exhibited specific features
similar to tumor derived MSCs. Whilst there was no evidence of malignant
transformation in the cystic tissue, our results provide evidence that this
abnormal tissue has malignant potential. MSCs are considered important players in
the tumor microenvironment and they have been closely linked to regulation of
tumor survival, growth, and progression. Thus, early lesion resection also in
asymptomatic patients might be indicated to exclude that the microenvironment may
be potentially permissive to cancer development.
PMID- 28493305
TI - Editorial.
PMID- 28493306
TI - Decisions on Hydraulic Fracturing Must Be Science-Based.
PMID- 28493307
TI - Hepatitis B virus screening and reactivation and management of patients with
nasopharyngeal carcinoma: A large-scale, big-data intelligence platform-based
analysis from an endemic area.
AB - BACKGROUND: Chemotherapy, target therapy, and immunotherapy are increasingly
being used in the systematic treatment of nasopharyngeal carcinoma (NPC), during
which the occurrence of hepatitis B virus (HBV) reactivation might increase.
However, data regarding HBV screening and reactivation and the clinical
management of NPC patients with HBV infections are lacking. This study was aimed
at clarifying the risk of reactivation for NPC patients on different regimens
while providing evidence concerning HBV screening and management in an endemic
area. METHODS: With the NPC database from an established big-data intelligence
platform at Sun Yat-Sen University Cancer Center in China, NPC patients who were
diagnosed between 2008 and 2016 and underwent HBV screening and regular
monitoring of liver enzymes and HBV deoxyribonucleic acid (DNA) were analyzed.
RESULTS: Among the 46,919 patients identified, the HBV screening rate was 24.8%
(11,616 of 46,919). Among the screened patients with an HBV infection, regular
monitoring of liver enzymes and HBV DNA occurred for 563 patients. The incidence
of HBV reactivation and HBV-related hepatitis was 9.1% (51 of 563) and 2.5% (14
of 563), respectively. The reactivation risk varied for different treatments and
regimens and ranged from 0.0% to 21.4%. Detectable baseline HBV DNA (odds ratio
[OR], 2.93; P < .01), the presence of liver metastasis at diagnosis (OR, 7.19; P
< .01), and antiviral prophylaxis (OR, 0.29; P < .01) were significantly
associated with reactivation. CONCLUSIONS: In NPC patients with chronic HBV
infections on high-risk regimens, the reactivation risk is similar to or exceeds
the risk associated with other immunosuppressive therapies for which screening
and prophylaxis are recommended. Our findings, therefore, support HBV screening
and prophylaxis for these patients, whereas regular monitoring might be
appropriate for patients with resolved HBV infections or those receiving low-risk
regimens. Cancer 2017;123:3540-9. (c) 2017 American Cancer Society.
PMID- 28493308
TI - North Central Cancer Treatment Group N0543 (Alliance): A phase 2 trial of
pharmacogenetic-based dosing of irinotecan, oxaliplatin, and capecitabine as
first-line therapy for patients with advanced small bowel adenocarcinoma.
AB - BACKGROUND: Oxaliplatin in combination with either 5-fluorouracil or capecitabine
is commonly used as first-line therapy for patients with small bowel
adenocarcinoma. The addition of irinotecan improves survival in other
gastrointestinal tumors but at the cost of hematologic toxicity. The authors
performed a phase 2 cooperative group study (North Central Cancer Treatment Group
N0543, Alliance) using genotype-dosed capecitabine, irinotecan, and oxaliplatin
(gCAPIRINOX), with dosing assigned based on UDP glucuronosyltransferase family 1
member A1 (UGT1A1) genotype to test: 1) whether the addition of irinotecan would
improve outcomes; and 2) whether UGT1A1 genotype-based dosing could optimize
tolerability. METHODS: Previously untreated patients with advanced small bowel
adenocarcinoma received irinotecan (day 1), oxaliplatin (day 1), and capecitabine
(days 2-15) in a 21-day cycle and were dosed with gCAPIRINOX according to
UGT1A1*28 genotypes (6/6, 6/7, and 7/7). RESULTS: A total of 33 patients (17 with
the 6/6 genotype, 10 with the 6/7 genotype, and 6 with the 7/7 genotype) were
enrolled from October 2007 to November 2013; 73% were male, with a mean age of 64
years (range, 41-77 years). Location of the primary tumor included the duodenum
(58%), jejunum (30%), and ileum (9%). The regimen yielded a confirmed response
rate of 37.5% (95% confidence interval, 21%-56%), with a median progression-free
survival of 8.9 months and a median overall survival of 13.4 months. Neither
hematologic toxicity (grade >=3 in 52.9%, 30.0%, and 33.3%, respectively, of the
6/6, 6/7, and 7/7 genotype groups) nor tumor response rate (41.2%, 33%, and 33%,
respectively) were found to differ significantly by UGT1A1 genotype. CONCLUSIONS:
UGT1A1 genotype-directed dosing (gCAPIRINOX) appears to be feasible with
favorable rates of hematologic toxicity compared with prior 3-drug studies in
unselected patients. Larger studies would be needed to determine the regimen's
comparability to oxaliplatin and capecitabine (CapeOx) alone or if
response/toxicity differs among patients with different UGT1A1 genotypes. Cancer
2017;123:3494-501. (c) 2017 American Cancer Society.
PMID- 28493309
TI - Effect of Nanoemulsified and Microencapsulated Mexican Oregano (Lippia graveolens
Kunth) Essential Oil Coatings on Quality of Fresh Pork Meat.
AB - Fresh meat is a highly perishable food. This work aimed to evaluate the influence
of Mexican oregano (Lippia graveolens Kunth) incorporated into active coatings
(ACs) spread on fresh pork meat as free (FEO), nanoemulsified (NEO), and
microencapsulated (MEO) essential oil (EO), on its microbiological,
physicochemical and sensory properties during 15 d at 4 +/- 1 degrees C. Thymol
and gamma-terpinene were identified in the EO. In vitro effect of 2.85 mg EO/cm2
was tested against Brochothrix thermosphacta, Micrococcus luteus, Lactobacillus
plantarum, Pseudomonas fragi, and Salmonella Infantis. FEO antioxidant capacity
(DPPH assay) was significantly higher than that of thymol, NEO and MEO (93.53%,
89.92%, 77.79%, and 78.50% inhibition, respectively), and similar to BHA (96.03%)
and gallic acid (95.57%). FEO, NEO, and MEO ACs on meat caused growth inhibition
of lactic acid bacteria (5 log population reduction) and Pseudomonas spp. (4 log
reduction), whereas <=1.5 log population reduction was observed for B.
thermosphacta and Salmonella Infantis. Meat microbiota was more efficiently
controlled by MEO than by FEO or NEO. ACs delayed lipid and oxymyoglobin
oxidation of fresh pork meat. After 15 d of cold storage meat added with EO
coatings was desirable for panelists, whereas untreated (UT) samples were
undesirable. Active coatings are a significant alternative method for fresh meat
preservation.
PMID- 28493310
TI - Evolution of Heterogeneous Mixed Siliciclastic/Carbonate Aquifers Containing
Metastable Sediments.
AB - Mixed carbonate and siliciclastic marine sediments commonly become freshwater
aquifers in eastern coastal regions of the United States and many other global
locations. As these deposits age, the carbonate fraction of the sediment is
commonly removed by dissolution and the aquifer can become a solely siliciclastic
system or contain zones or beds of pure quartz sand. During aquifer evolution,
the sediment grain size characteristics, hydraulic conductivity, and porosity
change. An investigation of these changes using mixed carbonate/siliciclastic
sediment samples collected from a modern barrier island beach in southern Florida
showed that the average mean grain diameter decreased with removal of the
carbonate fraction, but the average hydraulic conductivity and porosity increased
slightly, but not to statistical significance. This counterintuitive result
occurs because of the change in the pore types from a combined shelter and
intergranular pore system producing a dual porosity system in the mixed sediments
to a single intergranular pore system in the siliciclastic sediment fraction.
Within the mixed carbonate/siliciclastic sediment, in the pure carbonate
fraction, large shell fractions form grain-supported large pores, which become
filled with sand-sized quartz as the shell fragments decrease in size or as the
sediment becomes compacted. The hydraulic conductivity increases because the
shell fragments that were oriented perpendicular to flow caused an increase in
the length of the flow path, or a larger scale tortuosity, compared with the flow
through pure quartz sand.
PMID- 28493311
TI - ETHQV6.3 is involved in melon climacteric fruit ripening and is encoded by a NAC
domain transcription factor.
AB - Fruit ripening is divided into climacteric and non-climacteric types depending on
the presence or absence of a transient rise in respiration rate and the
production of autocatalytic ethylene. Melon is ideal for the study of fruit
ripening, as both climacteric and non-climacteric varieties exist. Two
introgressions of the non-climacteric accession PI 161375, encompassed in the
QTLs ETHQB3.5 and ETHQV6.3, into the non-climacteric 'Piel de Sapo' background
are able to induce climacteric ripening independently. We report that the gene
underlying ETHQV6.3 is MELO3C016540 (CmNAC-NOR), encoding a NAC (NAM, ATAF1,2,
CUC2) transcription factor that is closely related to the tomato NOR (non
ripening) gene. CmNAC-NOR was functionally validated through the identification
of two TILLING lines carrying non-synonymous mutations in the conserved NAC
domain region. In an otherwise highly climacteric genetic background, both
mutations provoked a significant delay in the onset of fruit ripening and in the
biosynthesis of ethylene. The PI 161375 allele of ETHQV6.3 is similar to that of
climacteric lines of the cantalupensis type and, when introgressed into the non
climacteric 'Piel de Sapo', partially restores its climacteric ripening capacity.
CmNAC-NOR is expressed in fruit flesh of both climacteric and non-climacteric
lines, suggesting that the causal mutation may not be acting at the
transcriptional level. The use of a comparative genetic approach in a species
with both climacteric and non-climacteric ripening is a powerful strategy to
dissect the complex mechanisms regulating the onset of fruit ripening.
PMID- 28493313
TI - The EPR Spectrum of Triplet Mesitylphosphinidene: Reassignment and New
Assignment.
AB - Low-temperature UV-photolysis of mesitylphosphiranes under highly anaerobic
conditions leads to the formation of the triplet mesitylphosphinidene (MesP). The
recorded X-band EPR spectrum of triplet MesP and the derived zero-field splitting
parameter D=4.116 cm-1 differ significantly from those reported previously for
this intermediate. New magnetic parameters of mesitylphosphinidene are discussed
along with the results of DFT calculations.
PMID- 28493312
TI - Minor allergen patterns in birch pollen allergen products-A question of pollen?
AB - BACKGROUND: Contrary to the scientific differentiation between major and minor
allergens, the regulatory framework controlling allergen products in the EU
distinguishes relevant and non-relevant allergens. Given the lack of knowledge on
their clinical relevance, minor allergens are usually not controlled by allergen
product specifications. Especially, in birch pollen (BP) allergen products, minor
allergens are commonly disregarded. OBJECTIVES: To quantify three minor allergens
in BP allergen products from different manufacturers and to assess the influence
of the utilized BP on minor allergen patterns. METHODS: Apart from common quality
parameters such as Bet v 1 content, Bet v 4, Bet v 6 and Bet v 7 were quantified
in 70 BP allergen product batches from six manufacturers, using ELISA systems
developed in-house. Batch-to-batch variability was checked for agreement with a
variability margin of 50%-200% from mean of the given batches for individual
allergen content. Subsequently, minor allergen patterns were generated via
multidimensional scaling and related to information on the pollen lots used in
production of the respective product batches. RESULTS: Like the already
established Bet v 4 ELISA, the ELISA systems for quantification of Bet v 6 and
Bet v 7 were successfully validated. Differences in minor allergen content
between products and batch-to-batch consistency were observed. Correlations
between minor and major allergen content were low to moderate. About 20% of
batches exceeded the variability margin for at least one minor allergen.
Interestingly, these fluctuations could not in all cases be linked to the use of
certain BP lots. CONCLUSIONS AND CLINICAL RELEVANCE: The impact of the observed
minor allergen variability on safety and efficacy of BP allergen products can
currently not be estimated. As the described differences could only in few cases
be related to the used pollen lots, it is evident that additional factors
influence minor allergens in BP allergen products.
PMID- 28493314
TI - Use of LC-HRMS in full scan-XIC mode for multi-analyte urine drug testing - a
step towards a 'black-box' solution?
AB - The influx of new psychoactive substances (NPS) has created a need for improved
methods for drug testing in toxicology laboratories. The aim of this work was to
design, validate and apply a multi-analyte liquid chromatography-high-resolution
mass spectrometry (LC-HRMS) method for screening of 148 target analytes belonging
to the NPS class, plant alkaloids and new psychoactive therapeutic drugs. The
analytical method used a fivefold dilution of urine with nine deuterated internal
standards and injection of 2 MUl. The LC system involved a 2.0 MUm 100 * 2.0 mm
YMC-UltraHT Hydrosphere-C18 column and gradient elution with a flow rate of 0.5
ml/min and a total analysis time of 6.0 min. Solvent A consisted of 10 mmol/l
ammonium formate and 0.005% formic acid, pH 4.8, and Solvent B was methanol with
10 mmol/l ammonium formate and 0.005% formic acid. The HRMS (Q Exactive, Thermo
Scientific) used a heated electrospray interface and was operated in positive
mode with 70 000 resolution. The scan range was 100-650 Da, and data for
extracted ion chromatograms used +/- 10 ppm tolerance. Product ion monitoring was
applied for confirmation analysis and for some selected analytes also for
screening. Method validation demonstrated limited influence from urine matrix,
linear response within the measuring range (typically 0.1-1.0 MUg/ml) and
acceptable imprecision in quantification (CV <15%). A few analytes were found to
be unstable in urine upon storage. The method was successfully applied for
routine drug testing of 17 936 unknown samples, of which 2715 (15%) contained 52
of the 148 analytes. It is concluded that the method design based on simple
dilution of urine and using LC-HRMS in extracted ion chromatogram mode may offer
an analytical system for urine drug testing that fulfils the requirement of a
'black box' solution and can replace immunochemical screening applied on
autoanalyzers. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28493315
TI - Robust mislabel logistic regression without modeling mislabel probabilities.
AB - Logistic regression is among the most widely used statistical methods for linear
discriminant analysis. In many applications, we only observe possibly mislabeled
responses. Fitting a conventional logistic regression can then lead to biased
estimation. One common resolution is to fit a mislabel logistic regression model,
which takes into consideration of mislabeled responses. Another common method is
to adopt a robust M-estimation by down-weighting suspected instances. In this
work, we propose a new robust mislabel logistic regression based on gamma
divergence. Our proposal possesses two advantageous features: (1) It does not
need to model the mislabel probabilities. (2) The minimum gamma-divergence
estimation leads to a weighted estimating equation without the need to include
any bias correction term, that is, it is automatically bias-corrected. These
features make the proposed gamma-logistic regression more robust in model fitting
and more intuitive for model interpretation through a simple weighting scheme.
Our method is also easy to implement, and two types of algorithms are included.
Simulation studies and the Pima data application are presented to demonstrate the
performance of gamma-logistic regression.
PMID- 28493316
TI - A profile of lipid dysregulation in harlequin ichthyosis.
PMID- 28493318
TI - Zinc-Catalyzed Synthesis of Allylsilanes by Si-H Bond Insertion of Vinyl
Carbenoids Generated from Cyclopropenes.
AB - Allylsilanes have long been recognized as valuable building blocks for organic
synthesis. A zinc-catalyzed reaction of cyclopropenes and hydrosilanes provides a
convenient route to these versatile unsaturated organosilanes. In this
transformation, ZnBr2 serves as an efficient catalyst, allowing the generation of
a zinc vinyl carbenoid intermediate, which is subsequently involved in a Si-H
bond insertion. The process shows broad scope, and is amenable to substituted and
functionalized cyclopropenes or the functionalization of polysiloxanes. Moreover,
zinc-catalyzed carbene insertion into a Ge-H bond is reported for the first time.
PMID- 28493317
TI - Attachment and Biofilm Formation by Selected Strains of Salmonella enterica and
Entrohemorrhagic Escherichia coli of Fresh Produce Origin.
AB - This study compared the abilities of selected Salmonella enterica and
enterohemorrhagic Escherichia coli (EHEC) strains of fresh produce origin to form
biofilms on polystyrene surface and to attach to alfalfa and bean sprouts. Each
of the 7 S. enterica and 4 EHEC inocula (2 mL; 107 CFU/mL) was placed in 6
different broths in 24-well polystyrene tissue culture plates at 28 degrees C
for 1 to 7 d. Developed biofilms were quantified using the crystal violet binding
assay. In a separate experiment, alfalfa and mung bean sprouts (5 g) were exposed
to 25 mL inocula (107 CFU/mL) of S. enterica or EHEC at 22 degrees C for 2 h
with shaking at 40 rpm. Contaminated sprouts were thoroughly rinsed and
homogenized in 0.1% peptone water, and bacteria attached to sprouts were
enumerated. Biofilm mass accumulated on polystyrene surface increased with
incubation time (P < 0.05). Among the microbiological media used, LB no salt
(NaCl) broth better supported biofilm development (P < 0.05). Two EHEC strains
formed more biofilms than the Salmonella and other two EHEC strains (P < 0.05).
However, more Salmonella cells (5.66 log CFU/g) attached to sprouts than EHEC
cells (3.46 log CFU/g). Both Salmonella and EHEC attached in higher numbers to
mung bean, than alfalfa, sprouts (P < 0.05).
PMID- 28493319
TI - An Elitist Multiobjective Tabu Search for Optimal Design of Groundwater
Remediation Systems.
AB - This study presents a new multiobjective evolutionary algorithm (MOEA), the
elitist multiobjective tabu search (EMOTS), and incorporates it with
MODFLOW/MT3DMS to develop a groundwater simulation-optimization (SO) framework
based on modular design for optimal design of groundwater remediation systems
using pump-and-treat (PAT) technique. The most notable improvement of EMOTS over
the original multiple objective tabu search (MOTS) lies in the elitist strategy,
selection strategy, and neighborhood move rule. The elitist strategy is to
maintain all nondominated solutions within later search process for better
converging to the true Pareto front. The elitism-based selection operator is
modified to choose two most remote solutions from current candidate list as seed
solutions to increase the diversity of searching space. Moreover, neighborhood
solutions are uniformly generated using the Latin hypercube sampling (LHS) in the
bounded neighborhood space around each seed solution. To demonstrate the
performance of the EMOTS, we consider a synthetic groundwater remediation
example. Problem formulations consist of two objective functions with continuous
decision variables of pumping rates while meeting water quality requirements.
Especially, sensitivity analysis is evaluated through the synthetic case for
determination of optimal combination of the heuristic parameters. Furthermore,
the EMOTS is successfully applied to evaluate remediation options at the field
site of the Massachusetts Military Reservation (MMR) in Cape Cod, Massachusetts.
With both the hypothetical and the large-scale field remediation sites, the EMOTS
based SO framework is demonstrated to outperform the original MOTS in achieving
the performance metrics of optimality and diversity of nondominated frontiers
with desirable stability and robustness.
PMID- 28493320
TI - Post Graduate Course.
PMID- 28493322
TI - Three-year cancer incidence in Blantyre, Malawi (2008-2010).
AB - In this paper, we present incidence rates of different cancers calculated for the
population of Blantyre, Malawi for the period 2008-2010, using data from the
Malawi Cancer Registry. Active methods were used for case finding, with standard
checks for accuracy and validity performed in CanReg 4. During this 3-year
period, a total of 3,711 cases were registered comprising 1,643 men (an estimated
age-standardized incidence rate (ASR) of 169.8 per 100,000) and 2,068 women (ASR
238.7 per 105 ). Kaposi sarcoma (KS) was the most common cancer in men (40.5% of
all cancers in men; ASR 54.0 per 105 ) while cervical cancer was the commonest in
women (33.3%; ASR 88.6 per 105 ). The incidence rates for esophageal cancer
remain one of the highest in the world (ASR 30.9 per 100,000 in men, 22.1 per
100,000 in women). Incidence of cancer of the prostate is relatively low in
Blantyre (5.1%; ASR 16.4 per 105 ), compared with elsewhere in Africa. In
childhood, the cancer spectrum is dominated by Burkitt lymphoma (32.5% ASR 90.9
per 106 ) followed by Wilms tumor (11.3%; ASR 35.9 per 106 ) and pediatric KS
(11.0%; ASR 31.1 per 106 ). The overall percentage of cases with histological
verification was 47.5%, a slight improvement from 42.4% in late 1990s also
indicating successful case finding outside laboratories.
PMID- 28493321
TI - Local genes for local bacteria: Evidence of allopatry in the genomes of
transatlantic Campylobacter populations.
AB - The genetic structure of bacterial populations can be related to geographical
locations of isolation. In some species, there is a strong correlation between
geographical distance and genetic distance, which can be caused by different
evolutionary mechanisms. Patterns of ancient admixture in Helicobacter pylori can
be reconstructed in concordance with past human migration, whereas in
Mycobacterium tuberculosis it is the lack of recombination that causes allopatric
clusters. In Campylobacter, analyses of genomic data and molecular typing have
been successful in determining the reservoir host species, but not geographical
origin. We investigated biogeographical variation in highly recombining genes to
determine the extent of clustering between genomes from geographically distinct
Campylobacter populations. Whole-genome sequences from 294 Campylobacter isolates
from North America and the UK were analysed. Isolates from within the same
country shared more recently recombined DNA than isolates from different
countries. Using 15 UK/American closely matched pairs of isolates that shared
ancestors, we identify regions that have frequently and recently recombined to
test their correlation with geographical origin. The seven genes that
demonstrated the greatest clustering by geography were used in an attribution
model to infer geographical origin which was tested using a further 383 UK
clinical isolates to detect signatures of recent foreign travel. Patient records
indicated that in 46 cases, travel abroad had occurred <2 weeks prior to
sampling, and genomic analysis identified that 34 (74%) of these isolates were of
a non-UK origin. Identification of biogeographical markers in Campylobacter
genomes will contribute to improved source attribution of clinical Campylobacter
infection and inform intervention strategies to reduce campylobacteriosis.
PMID- 28493323
TI - Early Changes of the Cortical Micro-Channel System in the Bare Area of the Joints
of Patients With Rheumatoid Arthritis.
AB - OBJECTIVE: To characterize the specific structural properties of the erosion
prone bare area of the human joint, and to search for early microstructural
changes in this region during rheumatoid arthritis (RA). METHODS: In the initial
part of the study, human cadaveric hand joints were examined for exact
localization of the bare area of the metacarpal heads, followed by detection of
cortical micro-channels (CoMiCs) in this region by high-resolution peripheral
quantitative computed tomography (HR-pQCT) and, after anatomic dissection,
validation of the presence of CoMiCs by micro-computed tomography (micro-CT). In
the second part of the study, the number and distribution of CoMiCs were analyzed
in 107 RA patients compared to 105 healthy individuals of similar age and sex
distribution. RESULTS: Investigation by HR-pQCT combined with adaptive
thresholding allowed the detection of CoMiCs in the bare area of human cadaveric
joints. The existence of CoMiCs in the bare area was additionally validated by
micro-CT. In healthy individuals, the number of CoMiCs increased with age. RA
patients showed significantly more CoMiCs compared to healthy individuals (mean
+/- SD 112.9 +/- 54.7/joint versus 75.2 +/- 41.9/joint; P < 0.001), with 20-49
year-old RA patients exhibiting similar numbers of CoMiCs as observed in healthy
individuals older than age 65 years. Importantly, CoMiCs were already found in RA
patients very early in their disease course, with enrichment in the erosion-prone
radial side of the joint. CONCLUSION: CoMiCs represent a new form of structural
change in the joints of patients with RA. Although the number of CoMiCs increases
with age, RA patients develop CoMiCs much earlier in life, and such changes can
even occur at the onset of the disease. CoMiCs therefore represent an interesting
new opportunity to assess structural changes in RA.
PMID- 28493324
TI - Level-specific amputations and resulting regenerative outcomes in the mouse
distal phalanx.
AB - Mouse digit tip regeneration involves an intricate coordinated regrowth of the
terminal phalanx, nail, dermis and epidermis. During this time, regenerating
digits undergo wound healing, blastema formation, and differentiation. However,
the regenerative response of the digit is dependent on the level of the
amputation. Amputation of <30% of the distal phalanx (P3), with part of the base
nail remaining, results in extensive digit regeneration. In contrast, >60% P3
removal results in no regeneration. This level-dependent regenerative ability of
the mouse digit provides a comparative model between regeneration and non
regeneration that may enable identification of specific factors critical to
regeneration. Although the ability to create regenerating and non-regenerating
conditions has been well established, the regenerative response between these
regions ("intermediate" zone) has received less scrutiny, and may add insight to
the regenerative processes, including the degree of histolysis, and the level of
blastema formation. The objective of this study is then to compare the
regeneration capacity between amputation levels within the regenerating (<30%),
intermediate (40-59%), and non-regenerating (>60%) regions. Results indicated
that regenerative and intermediate amputations led to significant histolysis and
blastema formation of the distal phalanx 14 days post-amputation. Unlike the
regenerating digits, intermediate amputations led to incomplete regeneration
whereby regrowth of the digits were not to the levels of the intact or
regenerating digits. Non-regenerating amputations did not exhibit significant
histolysis or blastema formation. Remarkably, the histolytic process resulted in
day 14 P3 lengths that were similar regardless of the initial amputation over
19%. The differences in histolysis, blastema formation and injury outcomes were
also marked by changes in the number of proliferating cells and osteoclasts.
Altogether, these results indicate that although intermediate amputations result
in histolysis and blastema formation similar to regenerating digits, the
resulting cellular composition of the blastema differs, contributing to
incomplete regeneration.
PMID- 28493325
TI - Developmental ecology of annual killifish Millerichthys robustus
(Cyprinodontiformes: Cynolebiidae).
AB - Populations of annual killifishes persist in temporary water bodies over the dry
season through the expression of diapause in their drought-resistant embryos.
Environmental cues may influence expression of the diapause phenotype during
embryonic incubation. Millerichthys robustus is the only annual killifish
distributed in North America. The aim of this review is to analyze the ecology of
M. robustus development and contrast this with that of annual killifishes in
austral locations. The temporary water bodies inhabited by M. robustus present
the following environmental conditions: flood, drought, and humidity. During the
flooding period, the environment presents the lowest temperatures, shortest
photoperiod, and highest precipitation, and embryos were found in diapause I. The
drought period features the highest temperatures and lowest precipitation, and
embryos were found in diapause II. In contrast, during the humid period at the
beginning of the rainy season, embryos were found in diapause I, II, and III,
associated with the longer photoperiod and high temperatures. These dynamics of
the diapause phenotypes can be explained by a combination of the strategies of
phenotypic plasticity during flood and drought periods, and bet-hedging during
the humid period. Moreover, the microenvironmental conditions in which embryos
were buried could influence developmental trajectories. Developmental Dynamics
246:802-806, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28493326
TI - Hyperglycaemia and aberrated insulin signalling stimulate tumour progression via
induction of the extracellular matrix component hyaluronan.
AB - Epidemiological studies have detected a higher incidence of various tumour
entities in diabetic patients. However, the underlying mechanisms remain
insufficiently understood. Glucose-derived pericellular and extracellular
hyaluronan (HA) promotes tumour progression and development. In our study, we
tested the hypothesis that a diabetic metabolic state, characterised by
hyperglycaemia and concomitant aberrant insulin signalling, stimulates tumour
progression via the induction of HA synthesis. In a streptozotocin-induced
diabetic nude mouse tumour xenograft model, hyperglycaemia and lack of insulin
caused an increased formation of tumour-associated HA-matrix, which in turn
accelerated tumour progression and neoangiogenesis. This process was effectively
attenuated by treatment with 4-methylumbelliferone, a pharmacological inhibitor
of HA-synthesis. To define the mechanisms behind these in vivo observations, we
investigated the impact of hyperglycaemia and insulin on the glucose metabolism
in oesophageal squamous cell cancer cells (ESCC). Hyperglycaemia induced HA
synthesis while insulin diminished HA production by directing glucose metabolites
to glycolysis. Vice versa, inhibition of glycolysis, either by knockdown of the
glycolytic key enzyme phosphofructokinase or by an experimental abrogation of
insulin signalling (knockdown of the insulin receptor and long-term treatment
with insulin) augmented HA synthesis. Consequently, these processes induced
invasion, anchorage-independent growth and adhesion of ESCC to endothelial cells
in vitro. Thus, the cellular shift in glucose usage from catabolism of glucose to
anabolism of HA driven by hyperglycaemia and insulin resistance may represent an
important link between diabetes and cancer progression. Hence, therapeutical
inhibition of HA synthesis may represent a promising approach for tumour
treatment in diabetic patients.
PMID- 28493327
TI - Burden of illness and healthcare resource use in United States patients with
sporadic inclusion body myositis.
AB - INTRODUCTION: We analyzed the burden of illness of sporadic inclusion body
myositis (sIBM) patients and the costs to the healthcare system. METHODS: A
retrospective cohort analysis of 333 sIBM patients aged >= 50 years was performed
using United States (U.S.) claims data. sIBM patients were matched in a 1:5 ratio
to randomly selected individuals with >=1 healthcare encounter within the year of
index date. RESULTS: sIBM patients presented with higher rates of disease- and
muscle-related conditions, such as myalgia, myositis, muscle weakness, dysphagia,
pneumonia, and falls. Use of healthcare resources, including physical therapy,
office visits, emergency room (ER) visits, and hospitalizations, was greater in
sIBM patients. This was also reflected in significantly higher overall healthcare
costs in the sIBM population driven mainly by more all-cause office visits, all
cause ER visits and hospitalizations. CONCLUSIONS: sIBM imposes a substantial
burden on U.S. patients in terms of additional healthcare usage and associated
costs. Muscle Nerve 56: 861-867, 2017.
PMID- 28493328
TI - Screening of 181 Patients With Antibody Deficiency for Deficiency of Adenosine
Deaminase 2 Sheds New Light on the Disease in Adulthood.
AB - OBJECTIVE: We aimed to test the relevance of deficiency of adenosine deaminase 2
(DADA2) in patients with antibody deficiency and describe the clinical picture of
the disease in adulthood. METHODS: We screened for DADA2 in a cohort of 181
patients with antibody deficiency with or without vascular lesions using next
generation sequencing and targeted Sanger sequencing. All mutations were
confirmed by determining the ADA2 enzymatic activity levels in dried plasma
spots. Clinical data and laboratory values were collected in a standardized
format. RESULTS: Following the diagnosis of 2 siblings in the index family, we
identified 9 additional affected patients with compound heterozygous or
homozygous CECR1 mutations, containing 6 novel and 4 previously published
mutations. The patients' age at evaluation ranged from 13 to 51 years, with a
median age of 22 years. Clinically, we saw a broad phenotype, ranging from
isolated antibody deficiency to recurrent strokes. All but 1 patient had low
numbers of memory B cells. Moreover, B cell function seemed to correlate with
inflammation. CONCLUSION: Taken together, our findings indicate that DADA2
presents not only with vasculopathy but also with an immunodeficiency of the B
cell compartment. Therefore, patients with antibody deficiency should be screened
for DADA2. Anti-tumor necrosis factor treatment might improve immunologic
features over time and might be considered in patients without vascular
manifestations but with elevated inflammation markers. Conservative management
has so far proven to be the choice for our less severely affected adolescent and
adult DADA2 patients; however, in patients with severe cytopenias and bone marrow
failure, hematopoietic stem cell transplantation should be considered.
PMID- 28493329
TI - Risk to heroin users of polydrug use of pregabalin or gabapentin.
AB - AIM: To examine the risk to heroin users of also using gabapentin or pregabalin
(gabapentoids). DESIGN: Multi-disciplinary study: we (a) examined trends in drug
related deaths and gabapentoid prescription data in England and Wales to test for
evidence that any increase in deaths mentioning gabapentin or pregabalin is
associated with trends in gabapentoid prescribing and is concomitant with opioid
use; (b) interviewed people with a history of heroin use about their polydrug use
involving gabapentin and pregabalin; and (c) studied the respiratory depressant
effects of pregabalin in the absence and presence of morphine in mice to
determine whether concomitant exposure increased the degree of respiratory
depression observed. SETTING: England and Wales. PARTICIPANTS: Interviews were
conducted with 30 participants (19 males, 11 female). MEASUREMENTS: (a) Office of
National Statistics drug-related deaths from 1 January 2004 to 31 December 2015
that mention both an opioid and pregabalin or gabapentin; (b) subjective views on
the availability, use, interactions and effects of polydrug use involving
pregabalin and gabapentin; and (c) rate and depth of respiration. RESULTS:
Pregabalin and gabapentin prescriptions increased approximately 24% per year from
1 million in 2004 to 10.5 million in 2015. The number of deaths involving
gabapentoids increased from fewer than one per year prior to 2009 to 137 in 2015;
79% of these deaths also involved opioids. The increase in deaths was correlated
highly with the increase in prescribing (correlation coefficient 0.94; 5%
increase in deaths per 100 000 increase in prescriptions). Heroin users described
pregabalin as easy to obtain. They suggested that the combination of heroin and
pregabalin reinforced the effects of heroin but were concerned it induced
'blackouts' and increased the risk of overdose. In mice, a low dose of S
pregabalin (20 mg/kg) that did not itself depress respiration reversed tolerance
to morphine depression of respiration (resulting in 35% depression of
respiration, P < 0.05), whereas a high dose of S-pregabalin (200 mg/kg) alone
depressed respiration and this effect summated with that of morphine.
CONCLUSIONS: For heroin users, the combination of opioids with gabapentin or
pregabalin potentially increases the risk of acute overdose death through either
reversal of tolerance or an additive effect of the drugs to depress respiration.
PMID- 28493330
TI - Improved panels for clinical immune phenotyping: Utilization of the violet laser.
AB - BACKGROUND: Clinical diagnostic laboratories are subject to numerous regulations
imposed by government agencies. Laboratory developed tests for flow cytometry
panels are essentially restricted to the use of analyte-specific reagents (ASR)
antibodies. With the advances in clinical flow cytometry systems, there is a
trend toward the utilization of blue/red/violet laser flow systems and 8 to 10
color panels. Currently, the selection of commercially available ASR antibodies
for the violet laser is very limited. The market is dominated by Brilliant Violet
421 (BV421) manufactured by BD Biosciences and Pacific Blue (PB) manufactured by
Beckman Coulter. In this study, we compare BV421 and PB conjugated ASR
antibodies. METHODS: Whole blood was stained and acquired on a Gallios flow
cytometer system. For single color staining, the stain index (SI) was calculated.
For the two panels, the compensation matrix was calculated and the performance of
the antibody cocktails analyzed in FCS Express. RESULTS: The results show that
five out of six tested BV421 conjugated antibodies have significantly higher SI
than their PB counterparts. Furthermore, BV421 antibodies require less
compensation for spillover than PB. Finally, BV421 conjugated antibodies give
better separation between negative and positive populations in the context of an
8 and 10 color panel without affecting the intensity of the other dyes.
CONCLUSIONS: Overall, using BV421 conjugated antibodies results in better
separation between populations compared to PB conjugated antibodies without
negatively affecting other fluorochromes in our panels. We conclude that the
BV421 conjugated ASR antibodies are currently the better available option for
clinical flow panels. (c) 2017 International Clinical Cytometry Society.
PMID- 28493332
TI - P-value calibration in multiple hypotheses testing.
AB - As p-values are the most common measures of evidence against a hypothesis, their
calibration with respect to null hypothesis conditional probability is important
in order to match frequentist unconditional inference with the Bayesian ones. The
Selke, Bayarri and Berger calibration is one of the most popular attempts to
obtain such a calibration. This relies on the theoretical sampling null
distribution of p-values, which is the well-known Uniform(0,1), but arising only
for specific sampling models. We generalize this calibration by considering a
sampling null distribution estimated from the data. It is possible to obtain such
an empirical null distribution, for instance, in the context of multiple testing
in which many p-values come from the null model. Such a context is purely
instrumental for the purposes of p-value calibration, and multiple testing still
needs to be considered with appropriate techniques. The new calibration proposed
here still remains a simple analytic formula like the original one under the
Uniform(0,1) and basically provides a stronger interpretation framework for the
widely used p-value. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28493333
TI - Treadmill exercise attenuates 3,4-methylenedioxymethamphetamine-induced memory
impairment through a decrease apoptosis in male rat hippocampus.
AB - 3,4-methylenedioxymethamphetamine (MDMA) leads to apoptosis in the hippocampus
with consequent induction of learning and memory impairment. In this study, we
have investigated the effects of treadmill exercise on memory in relation to
apoptosis and oxidative stress in the hippocampi of MDMA-treated rats. Male
Wistar rats received multiple intraperitoneal (IP) injections of MDMA (10 mg/kg)
and exercised for one month on a treadmill (simultaneously or asynchronously with
MDMA). We assessed memory function with the Morris water maze (MWM) test. Lipid
peroxidation (LPO) and expression of caspase 3, Bax, and Bcl-2 were examined by
the thiobarbituric acid assay (TBA) and western blot, respectively. Our results
showed that asynchronous treadmill exercise could significantly improve MDMA
induced memory impairment in the MWM test. Caspase 3 expression decreased in the
exercise group compared to the MDMA group. Although MDMA treatment caused an
increase in the Bax/Bcl-2 ratio, the treadmill exercise reduced this ratio.
Simultaneous exercise caused a reduction in lipid peroxidation in the
hippocampus. This data suggests that treadmill exercise can be a useful strategy
for treating memory impairment in persons with neurodegenerative disease and
stimulant drug users. (c) 2017 Wiley Periodicals, Inc.
PMID- 28493331
TI - Pilus biogenesis of Gram-positive bacteria: Roles of sortases and implications
for assembly.
AB - Successful adherence, colonization, and survival of Gram-positive bacteria
require surface proteins, and multiprotein assemblies called pili. These surface
appendages are attractive pharmacotherapeutic targets and understanding their
assembly mechanisms is essential for identifying a new class of 'anti-infectives'
that do not elicit microbial resistance. Molecular details of the Gram-negative
pilus assembly are available indepth, but the Gram-positive pilus biogenesis is
still an emerging field and investigations continue to reveal novel insights into
this process. Pilus biogenesis in Gram-positive bacteria is a biphasic process
that requires enzymes called pilus-sortases for assembly and a housekeeping
sortase for covalent attachment of the assembled pilus to the peptidoglycan cell
wall. Emerging structural and functional data indicate that there are at least
two groups of Gram-positive pili, which require either the Class C sortase or
Class B sortase in conjunction with LepA/SipA protein for major pilin
polymerization. This observation suggests two distinct modes of sortase-mediated
pilus biogenesis in Gram-positive bacteria. Here we review the structural and
functional biology of the pilus-sortases from select streptococcal pilus systems
and their role in Gram-positive pilus assembly.
PMID- 28493334
TI - Feasibility of an endotracheal tube-mounted camera for percutaneous dilatational
tracheostomy.
AB - BACKGROUND: Percutaneous dilatational tracheostomy (PDT) in critically ill
patients is often led by optical guidance with a bronchoscope. This is not
without its disadvantages. Therefore, we aimed to study the feasibility of a
recently introduced endotracheal tube-mounted camera (VivaSightTM-SL, ET View,
Misgav, Israel) in the guidance of PDT. METHODS: We studied 10 critically ill
patients who received PDT with a VivaSight-SL tube that was inserted prior to
tracheostomy for optical guidance. Visualization of the tracheal structures
(i.e., identification and monitoring of the thyroid, cricoid, and tracheal
cartilage and the posterior wall) and the quality of ventilation (before puncture
and during the tracheostomy) were rated on four-point Likert scales. Respiratory
variables were recorded, and blood gases were sampled before the interventions,
before the puncture and before the insertion of the tracheal cannula. RESULTS:
Visualization of the tracheal landmarks was rated as 'very good' or 'good' in all
but one case. Monitoring during the puncture and dilatation was also rated as
'very good' or 'good' in all but one. In the cases that were rated 'difficult',
the visualization and monitoring of the posterior wall of the trachea were the
main concerns. No changes in the respiratory variables or blood gases occurred
between the puncture and the insertion of the tracheal cannula. CONCLUSION:
Percutaneous dilatational tracheostomy with optical guidance from a tube-mounted
camera is feasible. Further studies comparing the camera tube with bronchoscopy
as the standard approach should be performed.
PMID- 28493335
TI - Response of Htr3a knockout mice to antidepressant treatment and chronic stress.
AB - BACKGROUND AND PURPOSE: It has recently been suggested that 5-HT3 receptor
blockade enhances the efficacy of selective 5-HT (serotonin) reuptake inhibitor
(SSRI) antidepressants and may reverse stress-induced deficits in rodents.
EXPERIMENTAL APPROACH: To further explore this hypothesis, we used mice lacking
the 5-HT3 receptor (Htr3a KO) and their wild-type (WT) controls to assess their
response in behavioural paradigms relevant to anxiety and depression. Mice were
studied under basal, antidepressant treatments and chronic social defeat stress
(CSDS) conditions. KEY RESULTS: In basal conditions, Htr3a KO mice displayed
anxiolytic- and antidepressant-like behaviours in the elevated plus maze, the
social interaction and the forced swim tests (FST), but behaved as WT mice in
response to acute citalopram in the FST. However, the effects of fluoxetine were
blunted in Htr3a KO mice in these same tests. In an in vitro electrophysiological
paradigm, a low-dose citalopram treatment triggered 5-HT1A receptor
desensitization only in the dorsal raphe nucleus of Htr3a KO, although a high
dose desensitized 5-HT1A autoreceptor function equally in Htr3a KO and WT mice,
suggesting that citalopram may become effective at lower doses when 5-HT3
receptors are inactivated. In addition, Htr3a deletion blocked CSDS-induced
modification in the cortical expression of two genes involved in oxidative
stress, CaMKIIa and SOD1. CONCLUSIONS AND IMPLICATIONS: Taken together, these
data show that Htr3a deletion promotes SSRI efficacy and prevents the occurrence
of stress-induced deleterious effects, suggesting that the 5-HT3 receptor may
represent an interesting target for the treatment of stress-related disorders.
PMID- 28493336
TI - De Novo Advanced Adult-Onset Offending: New Evidence from a Population of Federal
Correctional Clients.
AB - Adult antisocial behavior is almost always predated by delinquency during
childhood or adolescence; however, there is also evidence of adult-onset criminal
offending. This study examined this controversial subgroup of offenders using
self-reported and official data from a total population of federal correctional
clients selected from the Midwestern United States. Difference of means t-tests,
chi-square tests, and logistic regression models found that 11.7% of clients had
an adult onset of offending and 2.7% of clients (n = 23) had an onset occurring
at age 60 years or older. This group-introduced as de novo advanced adult-onset
offenders-had high socioeconomic status, mixed evidence of adverse childhood
experiences, and virtually no usage of drugs with the exception of alcohol. These
offenders were primarily convicted of social security and white-collar crimes and
evinced remarkably low psychopathology and criminal risk. More research is needed
to replicate the phenomenon of de novo advanced adult-onset offending.
PMID- 28493337
TI - Cas6 processes tight and relaxed repeat RNA via multiple mechanisms: A
hypothesis.
AB - RNA molecules are flexible yet foldable. Proteins must cope with this structural
duality when forming biologically active complexes with RNA. Recent studies of
the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs)-mediated
RNA immunity illustrate some remarkable mechanisms with which proteins interact
with RNA. Currently known structures of CRISPR-Cas6 endoribonucleases bound with
RNA suggest a conserved protein recognition mechanism mediated by RNA stem-loops.
However, a survey of CRISPR RNA reveals that many repeats either lack a
productive stem-loop (Relaxed) or possess stable but inhibitory structures
(Tight), which raises the question of how the enzyme processes structurally
diverse RNA. In reviewing recent literature, we propose a bivalent trapping and
an unwinding mechanism for CRISPR-Cas6 to interact with the Relaxed and the Tight
repeat RNA, respectively. Both mechanisms aim to create an identical RNA
conformation at the cleavage site for accurate processing.
PMID- 28493338
TI - Age-related changes of gustatory function depend on alteration of neuronal
circuits.
AB - Studies on age-related gustatory function report a reduction of the taste
function, but the degeneration of the peripheral papillae alone cannot explain
this reduction. In the present study, we apply psychophysics and gustatory event
related potentials (gERPs) to explore age-related differences in the processing
of gustatory information as indicated by the cerebral sources of the gERP. A
total of 96 subjects (47 female), subdivided into four groups with increasing
age, participated in the study. After olfactory and gustatory screening for
normal function, the subjects were invited to two sessions of gERP acquisition.
They received a randomized combination of five isointense basic tastants that
were presented at a medium level. At the same time, we recorded scalp
electroencephalography (EEG) from 128 scalp locations. Psychophysical testing for
smell and taste function exhibited a significant decrease with age. Topographical
analyses of the EEG delineated four basic topographical maps that explained the
processing of taste in the pre-decline age range, with sources inside the
relevant gustatory areas. The age-related change of gustatory processing was
associated with the absence of a specific map with sources inside the cerebellum
and posterior insula, and the temporal broadening of a map with sources in the
bilateral inferior frontal gyrus. These results confirm the hypothesis that the
reduction of taste function with aging is not only due to degradation of
gustatory peripheral tissues but is also related to different neural signatures
in the central nervous system.
PMID- 28493342
TI - Rapid-deployment aortic valve replacement versus standard bioprosthesis
implantation.
AB - OBJECTIVE: To compare the outcome and the 1-year hemodynamic results of the rapid
deployment Intuity valve versus the Perimount Magna bioprosthesis in matched
populations. METHODS: Between March 2014 and May 2015, 32 patients underwent
aortic valve replacement with the Intuity valve (Intuity-group). These patients
were compared to a matched population of Perimount valves implanted during the
same period of time (Perimount-group). Clinical data were compared and
echocardiographic 1-year follow-up was performed. RESULTS: There were more female
patients in the Intuity-group (47% vs 22%, p = 0.035); mean age was 78 +/- 5.6
and 72.5 +/- 6 years in the Intuity-group and Perimount-group (p < 0.001);
coronary disease was more common in the Intuity-group (65% vs 25%, p = 0.005).
Other characteristics were similar. Implants were 100% successful. Mean cross
clamp (50.3 +/- 25 vs 53 +/- 22 min, p = 0.004), cardiopulmonary bypass (68 +/-
27 vs 72 +/- 31.8 min; p = 0.006), and surgical times (156.8 +/- 54 vs 165 +/- 40
min; p = 0.018) were shorter with the Intuity despite more concomitant
procedures. Mean valve size was 23.7 mm (Intuity-group) and 24.1 mm (Perimount
group); hospital mortality was zero (Intuity-group) and 3% (Perimount-group); new
pacemaker implants were 6% (Intuity) and 3% (Perimount) (p = 0.55) and hospital
stay was equivalent. Mean gradients were: 9.9 +/- 3.4 (Intuity) versus 12.5 +/-
3.8 mmHg (Perimount) (p = 0.022) at discharge and 9 +/- 4 mmHg (Intuity) versus
14 +/- 4 mmHg (Perimount) (p = 0.02) at follow-up. At discharge, one Intuity
valve had 3+ aortic insufficiency (AI) which was unchanged at 1 year and will
require an intervention. Another patient had 1 + AI which progressed to 2+ at 1
year. There were no paravalvular leaks in the Perimount valves at discharge and
follow-up. CONCLUSION: Intuity valves showed lower gradients compared to
Perimount valves with the same mean size. Paravalvular leaks identified at the
time of implantation in Intuity valves need to be addressed at the time of
surgery.
PMID- 28493341
TI - Design and validation of the first cell-impermeant melatonin receptor agonist.
AB - BACKGROUND AND PURPOSE: The paradigm that GPCRs are able to prolong or initiate
cellular signalling through intracellular receptors recently emerged. Melatonin
binds to G protein-coupled MT1 and MT2 receptors. In contrast to most other
hormones targeting GPCRs, melatonin and its synthetic analogues are amphiphilic
molecules easily penetrating into cells, but the existence of intracellular
receptors is still unclear mainly due to a lack of appropriate tools.
EXPERIMENTAL APPROACH: We therefore designed and synthesized a series of
hydrophilic melatonin receptor ligands coupled to the Cy3 cyanin fluorophore to
reliably monitor its inability to penetrate cells. Two compounds, one lipophilic
and one hydrophilic, were then functionally characterized in terms of their
affinity for human and murine melatonin receptors expressed in HEK293 cells and
their signalling efficacy. KEY RESULTS: Among the different ligands, ICOA-13
showed the desired properties as it was cell-impermeant and bound to human and
mouse MT1 and MT2 receptors. ICOA-13 showed differential activities on melatonin
receptors ranging from partial to full agonistic properties for the Gi /cAMP and
ERK pathway and beta-arrestin 2 recruitment. Notably, ICOA-13 enabled us to
discriminate between Gi /cAMP signalling of the MT1 receptor initiated at the
cell surface and neuronal mitochondria. CONCLUSIONS AND IMPLICATIONS: We report
here the first cell-impermeant melatonin receptor agonist, ICOA-13, which allows
us to discriminate between signalling events initiated at the cell surface and
intracellular compartments. Detection of mitochondrial MT1 receptors may have an
important impact on the development of novel melatonin receptor ligands relevant
for neurodegenerative diseases, such as Huntington disease.
PMID- 28493343
TI - Direct Observation of Confined I- ???I2 ???I- Interactions in a Metal-Organic
Framework: Iodine Capture and Sensing.
AB - Herein a strategy is reported for capturing and sensing iodine by strong I- ???I2
???I- interaction, confined in a metal-organic framework, [Tb(Cu4 I4 )(ina)3
(DMF)] (1) (ina=isonicotinate). As revealed by single-crystal X-ray
crystallography, the uptaken I2 molecules directly contact the {Cu4 I4 }n chains,
virtually forming an electronically polarizable tetraiodide anion (I42- ) through
strong I- ???I2 ???I- interaction. As such, a quasi-copper-iodide layer of {Cu4
I5 }n with semiconducting characteristics results, leading to a significant
enhancement (Deltasigma =107 times) in electrical conductivity over the I2 -free
1. The effect observed is several orders of magnitude higher than those reported
due to iodine???aromatic interactions (Deltasigma =102 times) and by interactions
between I2 and a redox-active metal centre (Deltasigma =104 times). The drastic
enhancement in electrical conductivity was used to switch on/off an LED bulb,
suggesting the possibility of electrically sensing I2 .
PMID- 28493344
TI - Recreational Sporting Activity Vehicle-Related Deaths.
AB - Deaths occurring in the setting of nonprofessional, vehicle-related, recreational
sporting activities occurring on land or in water during warm or winter months
represent a diverse group of cases. These deaths tend to involve scenarios where
the participants are purposefully attempting to enjoy themselves prior to
experiencing sudden, catastrophic accidents resulting in lethal outcomes.
Ultimately, many of the deaths are related to the high speed at which these
vehicle-related activities normally occur. Three broad categories of factors may
play contributory roles in death: human factors, vehicle factors, and
environmental factors. A series of selected cases are presented, representing
examples of varying activity types, involving motorized and nonmotorized
vehicles, land and water activities, and warm weather and cold weather
environments. For each case, the various human, vehicle and environmental factors
believed to be contributory to the accident are considered, and strategies for
prevention of these and similar deaths involving recreational sporting vehicles
are presented.
PMID- 28493345
TI - IL-10 expression in pyramidal neurons after neuropathogenic coronaviral
infection.
AB - The apoptosis of pyramidal neurons in CA2 and CA3 subregions of the hippocampus
is induced after infection with Mu-3 virus (Mu-3), a neuropathogenic strain of
the JHM virus (JHMV), at 4-5 days post-inoculation (dpi). The viral antigens in
the hippocampus are mainly found in the CD11b-positive cells distributed in the
stratum oriens located outside the pyramidal layer, and only a few pyramidal
neurons are infected. Furthermore, the apoptotic cells, indicated as showing
caspase 3 (Cas3) activation, consist of a high number of uninfected cells.
Therefore, it is considered that the apoptotic lesions occur through the indirect
effects of infection, and not as a result of direct infection with Mu-3, similar
to the reported neuronal apoptosis in the hippocampus after other types of
infection. The apoptosis in the pyramidal neurons is accompanied by various types
of proinflammatory cytokines depending on the causative agents. Thus, the local
expression of proinflammatory cytokines was studied, revealing no correlation in
the distribution of cytokine expression with the subregions showing apoptosis.
However, the anti-inflammatory cytokine IL-10 was produced by pyramidal neurons
of CA2 and CA3 at 3 dpi when there is no destructive change or viral invasion in
the hippocampus.
PMID- 28493346
TI - No effect of targeted memory reactivation during slow-wave sleep on emotional
recognition memory.
AB - Recent work has suggested that the benefits of sleep for memory consolidation are
enhanced for highly salient (versus non-salient) memories. Using a technique
known as targeted memory reactivation, it is possible to selectively strengthen
newly learned memories by re-exposing the sleeping brain to auditory cues. The
aim of the current study was to examine whether emotionally salient memories are
also more responsive to targeted memory reactivation in slow-wave sleep than
neutral memories. In an initial training phase, participants memorised
emotionally negative and neutral pictures, which were each paired with a
semantically related sound. Recognition for the pictures was assessed before and
after a 90-min nap opportunity, during which half the sounds were re-presented
during slow-wave sleep (as assessed via online polysomnographic sleep
monitoring). We observed no effect of targeted memory reactivation on the
recognition of emotionally negative or neutral memories. Our results highlight
the importance of the memory paradigm used to assess targeted memory
reactivation, and suggest that the robust and durable nature of recognition
memory may make it an insensitive measure of behavioural targeted memory
reactivation benefits. To fully assess the impacts of targeted memory
reactivation on emotional memory processing in sleep, future studies should adopt
experimental paradigms that maximise the salience of emotional stimuli while also
providing a sensitive index of memory accuracy.
PMID- 28493347
TI - Effects of different loading protocols on the secondary stability and peri
implant bone density of the single implants in the posterior maxilla.
AB - BACKGROUND: Immediate or early loading of dental implants becomes a clinically
feasible concept. PURPOSE: The aim was to evaluate the effects of different
loading protocols (immediate, early, and delayed) on secondary stability and peri
implant bone density of single implants in the posterior maxilla. MATERIALS AND
METHODS: Thirty-nine implants (Dentium, South-Korea) were placed in 39 patients.
After placement, implant stability values (ISQ) and baseline peri-implant bone
density values derived from cone-beam computed tomography were recorded. Thirteen
implants were included randomly in each loading groups. The secondary ISQ values
were recorded during follow-up visits. Peri-implant bone density values were
measured 1 year after placement again. Data was statistically analyzed. RESULTS:
Immediate-loaded group showed the lowest ISQ values, 1 month after placement.
During the next follow-up visits, delayed-loaded group showed the lowest ISQ
values while other groups showed comparable results. Early loading increased the
peri-implant bone density greater than the other groups. CONCLUSIONS: The peri
implant bone of early-loaded implants was significantly denser than that of
immediate- and delayed-loaded implants, 1 year after placement. Density increment
can be judged as the radiological findings of loaded-bone, which may also reduce
the need for histomorphometric analysis of human biopsy to evaluate the bone
reaction around the implants.
PMID- 28493348
TI - Effect of Eye Opening on Single-Unit Activity and Local Field Potentials in the
Subthalamic Nucleus.
AB - BACKGROUND: Subthalamic nucleus deep brain stimulation (STN DBS) is an
established treatment in Parkinson's disease (PD). We investigate the effect of
eye opening on neuronal activity and local field potentials (LFPs) in the STN.
METHODS: We prospectively enrolled 25 PD patients undergoing STN DBS in our
institution. During DBS, single-unit activity (SUA) and LFPs were measured when
eyes were open and closed. As movement is known to result in changes in LFPs, we
tested response to eye opening in the presence and absence of movement. RESULTS:
Neither eye state nor arm movement has a significant influence on SUA recordings.
There is a statistically significant interaction between eye state and arm
movement (p < 0.05). In the presence of movement, STN SUA increase when eyes open
(p < 0.05). When eyes are closed, STN SUA decrease with movement (p < 0.05). STN
theta LFP oscillations decrease when eyes are open compared to closed,
irrespective of movement status (p < 0.05). DISCUSSION: STN activity is
influenced by eye state and arm movement. It is unclear whether this is
attributed to a change in the STN's role in oculomotor control or from a change
in attentional state. Understanding how physiologic normal activity alters neural
activity is critical for the optimization of DBS therapy, particularly in closed
loop neuromodulation.
PMID- 28493350
TI - Reproductive character displacement of female, but not male song discrimination
in an avian hybrid zone.
AB - Divergence of male sexual signals and female preferences for those signals often
maintains reproductive boundaries between closely related, co-occurring species.
However, contrasting sources of selection, such as interspecific competition, can
lead to weak divergence or even convergence of sexual signals in sympatry. When
signals converge, assortative mating can be maintained if the mating preferences
of females diverge in sympatry (reproductive character displacement; RCD), but
there are few explicit examples. Pied flycatchers (Ficedula hypoleuca) are
sympatric with collared flycatchers (F. albicollis) on the Baltic island of
Oland, where males from both species compete over nestboxes, their songs
converge, and the two species occasionally hybridize. We compare song
discrimination of male and female pied flycatchers on Oland and in an allopatric
population on the Swedish mainland. Using field choice trials, we show that male
pied flycatchers respond similarly to the songs of both species in sympatry and
allopatry, while female pied flycatchers express stronger discrimination against
heterospecific songs in sympatry than in allopatry. These results are consistent
with RCD of song discrimination of female pied flycatchers where they co-occur
with collared flycatchers, which should maintain species assortative mating
despite convergence of male sexual signals.
PMID- 28493349
TI - Adult acute supraglottitis: Analysis of 358 patients for predictors of airway
intervention.
AB - OBJECTIVES/HYPOTHESIS: Acute supraglottitis is a potentially life-threatening
condition due to rapid onset upper airway obstruction. The study aimed to
characterize adult acute supraglottitis patients and to recognize factors
associated with an aggressive disease course. STUDY DESIGN: Retrospective chart
review. METHODS: All adult acute supraglottitis patients admitted to a single
academic medical center between 2000 and 2014 were included and their medical
charts reviewed. The main outcome measures were airway intervention and
mortality. RESULTS: Three hundred fifty-eight patients were enrolled. Mean age
was 53 years (range, 16-92 years), with 62.8% males. Sore throat (79%) and
dysphagia (70.9%) were the most common symptoms. Stridor (3.6%), tachypnea
(5.7%), and dyspnea (6.4%) were uncommon but significantly associated with airway
intervention. The epiglottis was most commonly involved (67%). Involvement of the
epiglottis and aryepiglottic folds showed a trend of correlation to airway
intervention. Blood glucose levels, C-reactive protein (CRP) levels, and relative
neutrophilia were significantly higher in patients admitted to the intensive care
unit or requiring airway intervention. Thirty-four patients (9.5%) required
intensive care unit admission. Sixteen patients (4.4%) required airway
intervention. Recurrent episodes of supraglottitis, seen in 19 patients, were
more common in males (P = .048), and tended to have a more severe clinical
course, requiring more airway interventions (P = .005) and intensive care unit
admissions (P = .016). CONCLUSIONS: The typical high risk patient-a male, with
dyspnea and stridor, presenting with edema of the epiglottis and aryepiglottic
folds, elevated CRP, hyperglycemia, and a history of recurrent episodes-should
warrant more aggressive treatment and closer observation. LEVEL OF EVIDENCE: 4
Laryngoscope, 127:2106-2112, 2017.
PMID- 28493351
TI - Human Zika and West Nile virus neurological infections: What is the difference?
AB - The recent epidemic of West Nile Virus (WNV) infection in the United States was
associated with severe neurological disease in immunocompromised hosts, while the
emergence of Zika virus infection in the Americas has been notable for an
association with increased microcephaly in the fetuses of infected mothers. Rare
autopsies of WNV infected humans have shown multiple organ involvement with a
clear neurotropism. We have recently had the opportunity to examine the
distribution of Zika virus in autopsies of newborns from infected pregnancies.
While both viruses infect multiple organs, Zika appears to cause neurological
disease in the fetus through two different mechanisms. Infection during the first
trimester showed the potential to infect neural progenitor cells causing severe
developmental abnormalities, while infection later in gestation was associated
with meningeal infection and destructive ischemic lesions of the brain. Both
viruses infect kidney tubules but Zika shares a prominent hepatotropism
characteristic of other flaviviruses (e.g., Dengue). Limited transplacental Zika
infection would be consistent with restriction to primary maternal infections
with high viremia. In the absence of a vaccine, restriction of travel by
immunosuppressed and pregnant non-immune individuals to endemic regions seems
prudent.
PMID- 28493353
TI - Abstracts of the 51st Annual Scientific Meeting of the European Society for
Clinical Investigation, Genoa, Italy, 17th - 19th May 2017.
PMID- 28493352
TI - Should preoperative optimization of colorectal cancer patients supersede the
demands of the 62-day pathway?
PMID- 28493354
TI - Acral angioleiomyoma with tumoral calcinosis: a complication of the insertional
Achilles tendinopathy.
PMID- 28493355
TI - Consideration of difficulties and exit strategies in a case of face
allotransplantation resulting in failure.
AB - We describe the first rescue procedure in a case of total face
allotransplantation. The recipient was a 54-year-old man with severe
disfigurement of the entire face following an accidental gunshot injury 5 years
previously. The large defect included the maxilla, mandible, and mid-face. Full
face procurement was performed from a multiorgan cadaveric donor and was
allotransplanted to the recipient. The post-transplant induction
immunosuppressive regimen included ATG combined with tacrolimus, mycophenolate
mofetil, and prednisone, while maintenance was provided by the last three of
these. Although the early postoperative period was uneventful, squamous cell
carcinoma developed in the upper and lower extremities in the fifth postoperative
month, and post-transplant lymphoproliferative disorder (PTLD) occurred in the
sixth month postoperatively. Malignancies were treated, involving both surgical
and medical approaches. The patient developed opportunistic pulmonary and
cerebellar aspergillosis. In order to reduce the adverse affects and metabolic
and immunological load, the transplanted face was removed and replaced with a
free flap. Although the early postoperative period was promising, with the
transferred flap surviving totally and all vital signs and general status
appearing to be improving, the patient was eventually lost due to complicated
infectious and metabolic events. Although this case was unsuccessful, we suggest
that the immunological and metabolic load should be reduced as soon as stable
medical conditions are established in case of diagnosis of a situation involving
a high rate of mortality, such as PTLD and untreatable opportunistic infections.
This should include withdrawal of all immunosuppressive drugs and removal of all
allotransplanted tissues.
PMID- 28493356
TI - Closing the cervical cancer disparity gap.
PMID- 28493357
TI - Public Health Nursing and Transnational Agendas: Local to Global Health Advocacy.
PMID- 28493358
TI - Structural identification of degradants of moexipril by LC-MS/MS.
AB - A gradient LC-MS method was developed for the identification and characterization
of degradants of moexipril using liquid chromatography electrospray ionization
tandem mass spectrometry (LC/ESI-MS/MS). Moexipril was subjected to hydrolysis
(acid, base and neutral), oxidation, photolytic and thermal degradation
conditions as mentioned in ICH guidelines Q1A (R2). The drug degraded under
hydrolysis, oxidation and photolytic conditions, but it was stable under thermal
conditions. In total, five degradants were formed and separated on an Agilent XDB
C-18 column (4.6 * 150 mm, 5 MUm) in a gradient elution method. Four degradants
(D1, D2, D4 and D5) under acidic conditions, three degradants (D2, D3 and D4)
under basic conditions and three degradants (D1, D4 and D5) under neutral and
oxidative stress conditions were formed. In addition, two degradants (D4 and D5)
were formed under photolytic stress conditions. To elucidate the structures of
degradants, fragmentation of moexipril and its degradants was studied using LC
MS/MS experiments and accurate mass measurements (HRMS) data. The fragment ions
in the product ion tandem mass spectra of all the degradants were compared with
those of moexipril and assigned the probable structures for the degradants.
PMID- 28493359
TI - Verbal and Non-verbal Fluency in Adults with Developmental Dyslexia: Phonological
Processing or Executive Control Problems?
AB - The executive function of fluency describes the ability to generate items
according to specific rules. Production of words beginning with a certain letter
(phonemic fluency) is impaired in dyslexia, while generation of words belonging
to a certain semantic category (semantic fluency) is typically unimpaired.
However, in dyslexia, verbal fluency has generally been studied only in terms of
overall words produced. Furthermore, performance of adults with dyslexia on non
verbal design fluency tasks has not been explored but would indicate whether
deficits could be explained by executive control, rather than phonological
processing, difficulties. Phonemic, semantic and design fluency tasks were
presented to adults with dyslexia and without dyslexia, using fine-grained
performance measures and controlling for IQ. Hierarchical regressions indicated
that dyslexia predicted lower phonemic fluency, but not semantic or design
fluency. At the fine-grained level, dyslexia predicted a smaller number of
switches between subcategories on phonemic fluency, while dyslexia did not
predict the size of phonemically related clusters of items. Overall, the results
suggested that phonological processing problems were at the root of dyslexia
related fluency deficits; however, executive control difficulties could not be
completely ruled out as an alternative explanation. Developments in research
methodology, equating executive demands across fluency tasks, may resolve this
issue. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28493360
TI - Ethical reflection for medical electives.
AB - BACKGROUND: Forty per cent of UK medical students undertake their elective in a
developing country. Although these opportunities are often rewarding, students
encounter ethical questions, both in preparation and undertaking these projects.
The British Medical Association highlights three key ethical considerations for
elective students: clinical challenges, cultural challenges and impact on the
host institution. This report reflects on these considerations in the context of
a 4-week medical elective conducted by UK medical students in the Solomon
Islands. METHODS: Daily interviews were conducted with a focus group of six
medical students in the Solomon Islands over a 4-week elective period.
Descriptive analysis identified key themes. FINDINGS: Students were aware of
guidelines stating that they must act within their competency, but found it
difficult to assess their own skills and capacities in unfamiliar non-UK
settings. Culturally different societal and medical norms proved particularly
challenging. The impact of the student elective on the host hospital was also
larger than anticipated. DISCUSSION: In UK medical education, formal assessment
sets the benchmark for competency. Assessments cannot cover every situation
encountered on elective, and so students must therefore develop an alternative
benchmark to measure their ability. The lack of research into the impact of
electives on host institutions makes assessing the ethical nature of electives
challenging. The British Medical Association highlights three key ethical
considerations for elective students CONCLUSION: Prospective elective students
would benefit from pre-departure training on self-assessment of competency and
cultural awareness. UK medical schools have an ethical duty to encourage students
to consider the impact of their elective placements on host institutions.
PMID- 28493361
TI - Vertically Aligned Niobium Nanowire Arrays for Fast-Charging Micro
Supercapacitors.
AB - Planar micro-supercapacitors are attractive for system on chip technologies and
surface mount devices due to their large areal capacitance and energy/power
density compared to the traditional oxide-based capacitors. In the present work,
a novel material, niobium nanowires, in form of vertically aligned electrodes for
application in high performance planar micro-supercapacitors is introduced.
Specific capacitance of up to 1 kF m-2 (100 mF cm-2 ) with peak energy and power
density of 2 kJ m-2 (6.2 MJ m-3 or 1.7 mWh cm-3 ) and 150 kW m-2 (480 MW m-3 or
480 W cm-3 ), respectively, is achieved. This remarkable power density,
originating from the extremely low equivalent series resistance value of 0.27
Omega (2.49 uOmega m2 or 24.9 mOmega cm2 ) and large specific capacitance, is
among the highest for planar micro-supercapacitors electrodes made of
nanomaterials.
PMID- 28493363
TI - Salinity fluctuation influencing biological adaptation: growth dynamics and Na+
/K+ -ATPase activity in a euryhaline bacterium.
AB - Although salinity fluctuation is a prominent characteristic of many coastal
ecosystems, its effects on biological adaptation have not yet been fully
recognized. To test the salinity fluctuations on biological adaptation,
population growth dynamics and Na+ /K+ -ATPase activity were investigated in the
euryhaline bacterium Idiomarina sp. DYB, which was acclimated at different
salinity exposure levels, exposure times, and shifts in direction of salinity.
Results showed: (1) bacterial population growth dynamics and Na+ /K+ -ATPase
activity changed significantly in response to salinity fluctuation; (2) patterns
of variation in bacterial growth dynamics were related to exposure times, levels
of salinity, and shifts in direction of salinity change; (3) significant
tradeoffs were detected between growth rate (r) and carrying capacity (K) on the
one hand, and Na+ /K+ -ATPase activity on the other; and (4) beneficial
acclimation was confirmed in Idiomarina sp. DYB. In brief, this study
demonstrated that salinity fluctuation can change the population growth dynamics,
Na+ /K+ -ATPase activity, and tradeoffs between r, K, and Na+ /K+ -ATPase
activity, thus facilitating bacterial adaption in a changing environment. These
findings provide constructive information for determining biological response
patterns to environmental change.
PMID- 28493362
TI - Associations of prenatal and early life dietary inflammatory potential with
childhood adiposity and cardiometabolic risk in Project Viva.
AB - BACKGROUND: Limited information exists regarding the association between early
life diet and cardiometabolic risk. OBJECTIVES: Examine associations of dietary
inflammatory index (DII) in pregnancy and early childhood (3-5 years) with
adiposity, blood pressure and metabolic markers in mid-childhood (6-10 years).
METHODS: Among 992 mother-child pairs from Project Viva, a pre-birth cohort, we
examined associations of DII scores with outcomes using multivariable linear
regression adjusted for child age and sex and maternal age, BMI, education,
parity, smoking, race and income. RESULTS: Mean (SD) maternal DII in pregnancy
was -2.6(1.4) units and in child DII in early childhood was 0.3(0.7). Mean mid
childhood BMI z-score was 0.40(0.98) units. In boys only, DII in early childhood
was associated with higher BMIz (adjusted beta = 0.16 units per unit DII, 95%CI
0.02, 0.29), waist circumference (0.93 cm; -0.07, 1.92) and skin fold thicknesses
(1.12 mm; 0.01, 2.23). Dietary inflammatory index in the highest quartiles during
both pregnancy and in early childhood, compared to the lowest quartiles, was
associated with higher waist circumference (2.4 cm; 0.14, 4.6) in all children,
and BMIz in boys (0.78 units; 0.34, 1.22). Associations with BP and metabolic
markers were null. CONCLUSIONS: A pro-inflammatory diet in pregnancy and early
childhood may promote the development of adiposity.
PMID- 28493365
TI - Polymeric spatial resolution test patterns for mass spectrometry imaging using
nano-thermal analysis with atomic force microscopy.
AB - RATIONALE: As the spatial resolution of mass spectrometry imaging technologies
has begun to reach into the nanometer regime, finding readily available or easily
made resolution reference materials has become particularly challenging for
molecular imaging purposes. This paper describes the fabrication,
characterization and use of vertical line array polymeric spatial resolution test
patterns for nano-thermal analysis/atomic force microscopy/mass spectrometry
chemical imaging. METHODS: Test patterns of varied line width (0.7 or 1.0 MUm)
and spacing (0.7 or 1.0 MUm) were created in an ~1-MUm-thick poly(methyl
methacrylate) thin film using electron beam lithography. The patterns were
characterized by scanning electron microscopy, energy-dispersive X-ray
spectroscopy, atomic force microscopy topography and nano-thermal analysis/mass
spectrometry imaging. RESULTS: The efficacy of these polymeric test patterns for
the advancement of chemical imaging techniques was illustrated by their use to
judge the spatial resolution improvement achieved by heating the ionization
interface of the current instrument platform. The spatial resolution of the mass
spectral chemical images was estimated to be 1.4 MUm, based on the ability to
statistically distinguish 0.7-MUm-wide lines separated by 0.7-MUm-wide spacings
in those images when the interface cross was heated to 200 degrees C.
CONCLUSIONS: This work illustrates that e-beam lithography is a viable method to
create spatial resolution test patterns in a thin film of high molecular weight
polymer to allow unbiased judgment of intra-laboratory advancement and/or inter
laboratory comparison of instrument advances in nano-thermal analysis/atomic
force microscopy/mass spectrometry chemical imaging. Published in 2017. This
article is a U.S. Government work and is in the public domain in the USA.
PMID- 28493364
TI - Explicating the role of empathic processes in substance use disorders: A
conceptual framework and research agenda.
AB - ISSUES: Elucidating the role of empathic processes in developmental pathways to
substance use disorders could have important implications for prevention.
APPROACH: We searched the biomedical and social sciences literature to determine
what is known about empathy and psychopathological manifestations of severe lack
of empathy in the initiation, development and maintenance of psychoactive
substance use. Thirty-seven empirical studies were identified and formally
reviewed. KEY FINDINGS: Adults with alcohol and stimulant use disorders exhibited
detectable impairments in both cognitive and affective empathy, measured
behaviourally, neuroanatomically and by self-report, relative to controls. There
were no developmental studies specifically designed to test the role of empathy
in substance use pathways, but several studies that included measures of empathy
suggest that empathy may be protective. Studies on severe empathic deficits were
mixed regarding a unique role of empathy in substance use trajectories,
independent of interpersonal style, impulsivity and social deviance. Implications
and Conclusions. In the context of findings and methodological limitations of
this review, we recommend more rigorous examination of empathy across the
spectrum of substance use behaviour. Future work should utilise the following:
(i) prospective assessment of empathic capacity in substance abusers during and
following treatment; (ii) large, developmentally based prospective designs
beginning prior to substance initiation incorporating multiple measures of
empathy; (iii) assessment of the moderating role of gender, race and ethnicity;
and (iv) prospective study of empathy in children at elevated risk for substance
use disorders. [Massey SH, Newmark RL, Wakschlag LS. Explicating the role of
empathic processes in substance use disorders: A conceptual framework and
research agenda.
PMID- 28493366
TI - Frequent IDH2 R172 mutations in undifferentiated and poorly-differentiated
sinonasal carcinomas.
AB - Sinonasal undifferentiated carcinoma (SNUC) is a high-grade malignancy with
limited treatment options and poor outcome. A morphological spectrum of 47
sinonasal tumours including 17 (36.2%) SNUCs was analysed at genomic level.
Thirty carcinomas (cohort 1) were subjected to a hybridization exon-capture next
generation sequencing assay (MSK-IMPACTTM ) to interrogate somatic variants in
279 or 410 cancer-related genes. Seventeen sinonasal tumours (cohort 2) were
examined only for the presence of IDH1/2 exon 4 mutations by Sanger sequencing.
IDH2 R172 single nucleotide variants were overall detected in 14 (82.4%) SNUCs,
in two (20%) poorly-differentiated carcinomas with glandular/acinar
differentiation, and in one of two high-grade neuroendocrine carcinomas, large
cell type (HGNECs). No IDH2 mutation was detected in any of five olfactory
neuroblastomas or in any of five SMARCB1-deficient carcinomas. Among 12 IDH2
mutated cases in cohort 1, five (41.7%) harboured co-existing TP53 mutations,
four (33.3%) CDKN2A/2B loss-of-function alterations, four (33.3%) MYC
amplification, and three (25%) had concurrent SETD2 mutations. AKT1 E17K and KIT
D816V hotspot variants were each detected in one IDH2-mutated SNUC. The vast
majority of SNUCs and variable proportions of other poorly-differentiated
sinonasal carcinomas may be amenable to IDH2-targeted therapy. Copyright (c) 2017
Pathological Society of Great Britain and Ireland. Published by John Wiley &
Sons, Ltd.
PMID- 28493367
TI - Granulocyte-macrophage colony-stimulating factor, a potent adjuvant for
polarization to Th-17 pattern: an experience on HIV-1 vaccine model.
AB - Cytokines are mediators for polarization of immune response in vaccines. Studies
show that co-immunization of DNA vaccines with granulocyte-macrophage colony
stimulating factor (GM-CSF) can increase immune responses. Here, experimental
mice were immunized with HIV-1tat/pol/gag/env DNA vaccine with GM-CSF and boosted
with recombinant vaccine. Lymphocyte proliferation with Brdu and CTL activity, IL
4, IFN-gamma, IL-17 cytokines, total antibody, and IgG1 and IgG2a isotypes were
assessed with ELISA. Results show that GM-CSF as adjuvant in DNA immunization
significantly increased lymphocyte proliferation and IFN-gamma cytokines, but CTL
response was tiny increased. Also GM-CSF as adjuvant decreased IL-4 cytokine vs
mere vaccine group. IL-17 in the group that immunized with mixture of DNA
vaccine/GM-CSF was significantly increased vs DNA vaccine group. Result of total
antibody shows that GM-CSF increased antibody response in which both IgG1 and
IgG2a increased. Overall, results confirmed the beneficial effect of GM-CSF as
adjuvant to increase vaccine immunogenicity. The hallmark result of this study
was to increase IL-17 cytokine with DNA vaccine/GM-CSF immunized group. This
study for the first time provides the evidence of the potency of GM-CSF in the
induction of IL-17 in response to a vaccine, which is important for control of
infection such as HIV-1.
PMID- 28493368
TI - Microbial nitrous oxide emissions in dryland ecosystems: mechanisms, microbiome
and mitigation.
AB - Globally, drylands represent the largest terrestrial biome and are projected to
expand by 23% by the end of this century. Drylands are characterized by extremely
low levels of water and nutrients and exhibit highly heterogeneous distribution
in plants and biocrusts which make microbial processes shaping the dryland
functioning rather unique compared with other terrestrial ecosystems. Nitrous
oxide (N2 O) is a powerful greenhouse gas with ozone depletion potential. Despite
of the pivotal influences of microbial communities on the production and
consumption of N2 O, we have limited knowledge of the biological pathways and
mechanisms underpinning N2 O emissions from drylands, which are estimated to
account for 30% of total gaseous nitrogen emissions on Earth. In this article, we
describe the key microbial players and biological pathways regulating dryland N2
O emissions, and discuss how these processes will respond to emerging global
changes such as climate warming, extreme weather events and nitrogen deposition.
We also provide a conceptual framework to precisely manipulate the dryland
microbiome to mitigate N2 O emissions in situ using emerging technologies with
great specificity and efficacy. These cross-disciplinary efforts will enable the
development of novel and environmental-friendly microbiome-based solutions to
future mitigation strategies of climate change.
PMID- 28493369
TI - Efficacy and safety of secukinumab in Taiwanese patients with moderate to severe
plaque psoriasis: Subanalysis from ERASURE phase III study.
AB - The efficacy and safety of secukinumab, a fully human anti-interleukin-17A
monoclonal antibody, has been evaluated for moderate to severe plaque psoriasis
in global trials which have included a low proportion of Asian subjects. We
analyzed the efficacy and safety of secukinumab in Taiwanese patients in a phase
III global clinical trial (ERASURE). Fifty-one Taiwanese patients were randomized
into s.c. placebo, 150 and 300 mg secukinumab treatment groups. The proportions
of patients who achieved 75% or more improvement in Psoriasis Area and Severity
Index (PASI-75) at week 12 were 87.5% with 300 mg secukinumab, 70% with 150 mg
secukinumab, 0% with placebo. Of the patients receiving 300 mg secukinumab, 68.8%
achieved PASI-90 at week 12. Analysis of overall patients receiving 300 mg
secukinumab for 12 weeks showed that the proportion of PASI-75 responders was
less in patients with body mass index of 25 or more than less than 25. During the
entire 52 weeks, the incidence of adverse events (AE) was consistent with the
overall population in ERASURE. The most common AE (cases/per 100 patient-year)
during the entire treatment period were upper respiratory tract infection and
pruritus. The duration of upper respiratory tract infection per 100 patient-year
was approximately 399 days in placebo, 1261 days in 150 mg secukinumab and 1805
days in 300 mg secukinumab. The safety and efficacy of secukinumab in Taiwanese
patients was compatible with the global phase III study in the treatment of
moderate to severe plaque psoriasis.
PMID- 28493370
TI - Guided left ventricular lead placement for cardiac resynchronization therapy - an
opportunity for image integration: reply.
PMID- 28493371
TI - Effects of repetitive transcranial magnetic stimulation on improvement of
cognition in elderly patients with cognitive impairment: a systematic review and
meta-analysis.
AB - OBJECTIVE: This systematic review and meta-analysis aimed to examine the effects
of repetitive transcranial magnetic stimulation (rTMS) on cognitive function in
older patients with cognitive impairment. METHODS: A literature search was
performed for articles published in English using the 10 databases (MEDLINE,
EMBASE, PsycINFO, INSPEC, the Cumulative Index to Nursing and Allied Health
Literature Plus, AMED, Biological Sciences, ClinicalTrials.gov, the Cochrane
Central Register of Controlled Trials and the Cochrane Database of Systematic
Reviews) from their inception to May 2016. The primary outcome was cognitive
function as measured by the Mini-Mental State Examination or the Alzheimer's
Disease Assessment Scale-cognitive subscale. RESULTS: Seven RCTs were included in
the meta-analysis, with a sample of 107 active and 87 sham rTMS. Active rTMS was
found to be more effective in improving cognition (Hedges' g = 0.48; 95%
confidence interval 0.12 to 0.84). CONCLUSIONS: High-frequency rTMS showed a
benefit on cognition amongst older patients with mild to moderate Alzheimer's
disease. rTMS was shown to have great potential as a safe and well-tolerated
alternative intervention for cognition. Copyright (c) 2017 John Wiley & Sons,
Ltd.
PMID- 28493372
TI - Glycosuria and hyperglycemia in the neonatal period as the first clinical sign of
Fanconi-Bickel syndrome.
AB - Fanconi-Bickel syndrome is a rare inherited disease characterized by the
combination of hepatorenal glycogen accumulation, proximal renal tubular
dysfunction and impaired utilization of glucose and galactose. The first symptoms
of the disorder are recognized in late infancy as clinical characteristics
appear. Therapeutic approach is mainly conservative with supplements of calcium,
phosphate and vitamin D and small frequent feedings to avoid hypoglycemia. We
report 1 clinical case of very early diagnosis, a 19 days old baby girl, in which
the first clinical sign of the disease was the detection of glycosuria and
vomits. Serum alkaline phosphatase levels were very high without rickets. The
patient presented postprandial hyperglycemia and fasting hypoglycemia. A complete
24-hour glucose profile was obtained using a continuous glucose monitoring system
in real time, which was fundamental not only for the diagnosis but also for the
prevention of hypoglycemia. She received frequent small meals, galactose-free
milk diet, and oral intakes of calcium, phosphorum, bicarbonate and vitamin D
supplements with good evolution and normal height and weight gain.
PMID- 28493373
TI - The novel alphaB-crystallin (CRYAB) mutation p.D109G causes restrictive
cardiomyopathy.
AB - Restrictive cardiomyopathy (RCM) is a rare heart disease characterized by
diastolic dysfunction and atrial enlargement. The genetic etiology of RCM is not
completely known. We identified by a next-generation sequencing panel the novel
CRYAB missense mutation c.326A>G, p.D109G in a small family with RCM in
combination with skeletal myopathy with an early onset of the disease. CRYAB
encodes alphaB-crystallin, a member of the small heat shock protein family, which
is highly expressed in cardiac and skeletal muscle. In addition to in silico
prediction analysis, our structural analysis of explanted myocardial tissue of a
mutation carrier as well as in vitro cell transfection experiments revealed
abnormal protein aggregation of mutant alphaB-crystallin and desmin, supporting
the deleterious effect of this novel mutation. In conclusion, CRYAB appears to be
a novel RCM gene, which might have relevance for the molecular diagnosis and the
genetic counseling of further affected families in the future.
PMID- 28493374
TI - Polyphenols and Their Role in Obesity Management: A Systematic Review of
Randomized Clinical Trials.
AB - Polyphenols have been suggested to reduce body weight and modify body composition
through different mechanisms. These effects have been extensively studied in
animals and in vitro and to a lesser extent in humans. The aim of this review is
to consider the association between polyphenols and body weight status by
focusing on human intervention studies. We conducted a systematic literature
search in MEDLINE (via EBSCOhost), ProQuest CENTRAL, and Cochrane CENTRAL without
time restrictions. Randomized controlled trials assessing the effect of
polyphenols on weight and/or body composition in the overweight and/or obese
population were included. Nineteen studies met our inclusion criteria. Results
suggest that further research is required before supporting a potential role of
polyphenols in reducing weight in overweight and obese individuals (nine studies
showed a significant decrease in weight by a mean of 1.47 +/- 0.58 kg).
Nevertheless, several studies indicated that polyphenols might be effective in
preventing small increases in weight during periods of overfeeding rather than
reducing weight as such. The outcomes noted do not yet support polyphenol
supplementation as a complementary approach in weight loss diets. Further larger
trials with a duration of 12 months or more are needed to elucidate the effect of
polyphenols on body weight status. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28493375
TI - A systematic review of the psychological impact of false-positive colorectal
cancer screening: What is the role of the general practitioner?
AB - Screening for colorectal cancer (CRC) has both advantages (e.g. reduction in
morbidity and mortality) and disadvantages (e.g. false positives and distress). A
systematic review was therefore performed to improve our understanding of how
false-positive CRC screening results affect patients psychologically (and to make
recommendations for primary care). The PubMed, Embase, PsychINFO, CINAHL and
Cochrane databases were searched in October 2014 and supplemented in December
2016 to identify studies on the psychological impact of false-positive CRC
screening. Original studies were eligible when they assessed psychological impact
in a screening setting, provided they also included false-positive CRC screening
results. Two authors independently assessed 2,367 available manuscripts and
included seven. Heterogeneity in their outcome measures meant that data could not
be pooled. Two studies showed that a false-positive CRC screening result caused
some moderate psychological distress shortly before and after colonoscopy. The
remaining five studies illustrated that the psychological distress of patients
with true-positive and false-positive CRC screening results was comparable. We
conclude that a false-positive CRC screening result may cause some moderate
psychological distress, especially just before or after colonoscopy. We recommend
that general practitioners mention this when discussing CRC screening with
patients and monitor those with a false-positive outcome for psychological
distress.
PMID- 28493376
TI - Evaluation of the angiotensin II receptor blocker azilsartan medoxomil in African
American patients with hypertension.
AB - The efficacy and safety of azilsartan medoxomil (AZL-M) were evaluated in African
American patients with hypertension in a 6-week, double-blind, randomized,
placebo-controlled trial, for which the primary end point was change from
baseline in 24-hour mean systolic blood pressure (BP). There were 413 patients,
with a mean age of 52 years, 57% women, and baseline 24-hour BP of 146/91 mm Hg.
Treatment differences in 24-hour systolic BP between AZL-M 40 mg and placebo (
5.0 mm Hg; 95% confidence interval, -8.0 to -2.0) and AZL-M 80 mg and placebo (
7.8 mm Hg; 95% confidence interval, -10.7 to -4.9) were significant (P<=.001 vs
placebo for both comparisons). Changes in the clinic BPs were similar to the
ambulatory BP results. Incidence rates of adverse events were comparable among
the treatment groups, including those of a serious nature. In African-American
patients with hypertension, AZL-M significantly reduced ambulatory and clinic BPs
in a dose-dependent manner and was well tolerated.
PMID- 28493377
TI - Neonatal myeloid derived suppressor cells show reduced apoptosis and
immunosuppressive activity upon infection with Escherichia coli.
AB - Susceptibility to infection during the neonatal period and reduced control of
inflammation in neonates are attributed to immunosuppression persisting from
fetal life. Myeloid-derived suppressor cells (MDSCs) are immature myeloid
progenitors with suppressive activity and increased numbers in cord blood. We
hypothesized that MDSCs contribute to innate host defence in neonates, paralleled
by anti-inflammatory signalling.Phagocytic activity, infection induced apoptosis,
expression of B-cell lymphoma (Bcl)-2 family proteins, production of reactive
oxygen species (ROS), cytokine production and T-cell suppression of neonatal
granulocytic-MDSCs (G-MDSCs) after infection with Escherichia coli (E. coli) were
compared to neonatal autologous mature polymorphonuclear leukocytes (PMNs).
Phagocytic activity of G-MDSCs upon infection with E. coli was equal to that of
mature PMNs, however, apoptosis of G-MDSCs was decreased. G-MDSCs showed enhanced
Bcl-2-expression and lower ROS production compared to PMNs. Inhibition of Bcl-2
reduced apoptosis rates of G-MDSCs to that of mature PMNs. Induction of anti
inflammatory transforming growth factor beta (TGF-beta) was enhanced, while pro
inflammatory IL-8 decreased in G-MDSCs compared to PMNs. Infected G-MDSCs
strongly suppressed proliferation of T cells. We show a direct role of G-MDSCs
for anti-bacterial host defence. Prolonged survival and anti-inflammatory
capacity suggest that G-MDSCs are important for immune-regulation after bacterial
infection.
PMID- 28493378
TI - Blood pressure control and cardiovascular risk in hypertensive patients with type
2 diabetes: The German T2Target registry.
AB - Blood pressure control in patients with type 2 diabetes and hypertension is poor.
It is unclear how effectively general practitioners assess and treat such
patients. T2Target included hypertensive patients with type 2 diabetes mellitus
who had undergone ambulatory blood pressure monitoring within the past 3 months.
Recordings were analyzed by the general practitioner and an independent center
and the conclusions were compared. Nighttime hypertension was reported less
frequently by the general practitioner in comparison with central assessment
(43.9% vs 77.9%, P<.001), as were masked (4.0% vs 13.1%, P<.001) and isolated
office (4.4% vs 8.8%, P<.001) hypertension. A total of 13.9% of patients were
deemed to have controlled blood pressure (ambulatory blood pressure monitoring).
For the 784 patients with uncontrolled blood pressure, 40.7% underwent no change
to their antihypertensive treatment. Cardiovascular risk was underestimated, with
11.1% deemed to be at very high risk, in contrast to the 97.0% of patients by
central assessment. In conclusion, blood pressure control in hypertensive
patients with type 2 diabetes mellitus is poor and not accurately assessed by
office-based general practitioners, despite the use of ambulatory blood pressure
monitoring.
PMID- 28493379
TI - A highly selective fluorescent chemosensor for Cu2+ : synthesis and properties of
a rhodamine B-containing diarylethene.
AB - A diarylethene bearing a triazole-linked rhodamine B unit was synthesized. Its
fluorescent emission was significantly enhanced in the presence of protons or
Cu2+ due to transformation from the pirocyclic form to open-ring form. The
fluorescence was quenched sequentially upon irradiation with 297 nm light based
on the intramolecular fluorescence resonance energy transfer mechanism. In an
acetonitrile: water binary solvent (1: 1 v/v), the compound showed significant
fluorescent enhancement for Cu2+ compared with a wide range of tested metal ions
with a fast response and a limit of detection of 2.86 * 10-8 mol L-1 . Using
Cu2+ and UV light as the chemical inputs, and fluorescence intensity at 597 nm as
the output, a logic gate was developed at the molecular level. Moreover, the
compound can be used with a high accuracy to detect Cu2+ in a natural water
sample.
PMID- 28493380
TI - Post-Synthesis Amine Borane Functionalization of a Metal-Organic Framework and
Its Unusual Chemical Hydrogen Release Phenomenon.
AB - A novel strategy for post-synthesis amine borane functionalization of MOFs under
gas-solid phase transformation, utilizing gaseous diborane, is reported. The
covalently confined amine borane derivative decorated on the framework backbone
is stable when preserved at low temperature, but spontaneously liberates soft
chemical hydrogen at room temperature, leading to the development of an unusual
borenium type species (-NH=BH2+ ) ion-paired with a hydroborate anion.
Furthermore, the unsaturated amino borane (-NH=BH2 ) and the MU-iminodiborane (
MU-NHB2 H5 ) were detected as final products. A combination of DFT based
molecular dynamics simulations and solid state NMR spectroscopy, utilizing
isotopically enriched materials, were undertaken to unequivocally elucidate the
mechanistic pathways for H2 liberation.
PMID- 28493381
TI - Nitrogen-Doped Graphitic Porous Carbon Nanosheets Derived from In Situ Formed g
C3 N4 Templates for the Oxygen Reduction Reaction.
AB - Heteroatom-doped carbon materials have been considered as potential substitutes
for Pt-based electrocatalysts for the oxygen reduction reaction (ORR) in alkaline
fuel cells. Here we report the synthesis of oxygen-containing nitrogen-doped
carbon (ONC) nanosheets through the carbonization of a mixture that contained
glucose and dicyandiamide (DCDA). In situ formed graphitic carbon nitride (g-C3
N4 ) derived from DCDA provided a nitrogen-rich template, thereby facilitating
the formation of ONC nanosheets. The resultant ONC materials with high nitrogen
content, high specific surface areas, and highly mesoporous total volume
displayed excellent electrochemical performance, including a similar ORR onset
potential, half-potential, a higher diffusion-limited current, and excellent
tolerance to methanol than that of the commercial Pt/C catalyst, respectively.
Moreover, the ONC-850 nanosheet displayed high long-term durability even after
1000 cycles as well as a high electron transfer number of 3.92 (4.0 for Pt/C).
Additionally, this work provides deeper insight into these materials and a
versatile strategy for the synthesis of cost-effective 2D N-doped carbon
electrocatalysts.
PMID- 28493382
TI - Thiomaleimide Functionalization for Selective Biological Fluorescence Detection
of Peroxynitrite as Tested in HeLa and RAW 264.7 Cells.
AB - The role of fluorescent molecules in diagnosis, treatment as well as in
biomedical research has great current medicinal significance and is the focus of
concentrated effort across the scientific research spectrum. Related research
continues to reveal new practical sensing systems that bear enhanced features for
interfacing of substituted molecules with biological systems. As part of an
effort to better understand chalcogenide systems, a new dithiomaleimide BODIPY
(BDP-NGM) probe has been designed, synthesized and characterized. The
fluorescence of BDP-NGM was quenched by the incorporation of [3,4
bis(phenylthio)] on the maleimide-4-phenyl moiety which is, in turn, placed at
the meso-position of the BODIPY system. The probe shows a turn-on fluorescence
response upon reaction with ONOO- ; mass spectral evidence reveals peaks in
agreement with products involving oxidation of the sulfur groups to sulfone
groups. An about 18.0-fold emission intensity enhancement was found. By
comparison, the emission signal from another ROS/RNS, superoxide, gave a modest
turn on signal (~5.0-fold). The reaction is complete within 10 min, judging from
the monitoring of the turn-on fluorescence process; the detection limit was found
to be 0.4 MUm. BDP-NGM can be used for the detection of ONOO- under both acidic
and basic conditions. Live cell imaging showed that the current probe can be used
for the selective detection of ONOO- in living systems.
PMID- 28493383
TI - A large-scale assessment of temporal trends in meta-analyses using systematic
review reports from the Cochrane Library.
AB - INTRODUCTION: Previous studies suggest that many systematic reviews contain meta
analyses that display temporal trends, such as the first study's result being
more extreme than later studies' or a drift in the pooled estimate. We assessed
the extent and characteristics of temporal trends using all Cochrane intervention
reports published 2008-2012. METHODS: We selected the largest meta-analysis
within each report and analysed trends using methods including a Z-test (first
versus subsequent estimates); generalised least squares; and cumulative sum
charts. Predictors considered include meta-analysis size and review group.
RESULTS: Of 1288 meta-analyses containing at least 4 studies, the point estimate
from the first study was more extreme and in the same direction as the pooled
estimate in 738 (57%), with a statistically significant difference (first versus
subsequent) in 165 (13%). Generalised least squares indicated trends in 717
(56%); 18% of fixed effects analyses had at least one violation of cumulative sum
limits. For some methods, meta-analysis size was associated with temporal
patterns and use of a random effects model, but there was no consistent
association with review group. CONCLUSIONS: All results suggest that more meta
analyses demonstrate temporal patterns than would be expected by chance. Hence,
assuming the standard meta-analysis model without temporal trend is sometimes
inappropriate. Factors associated with trends are likely to be context specific.
PMID- 28493384
TI - Risk factors for single crowns supported by short (6-mm) implants in the
posterior region: A prospective clinical and radiographic study.
AB - BACKGROUND: The use of short implants is still not a consensus for challenging
clinical situations, such as unfavorable crown-to-implant (C/I) ratio. PURPOSE:
This prospective study evaluated the rates of prosthetic complications and
implant failure, the mean marginal bone loss of 6-mm dental implants with single
crowns in posterior regions and the potential risk factors. MATERIALS AND
METHODS: Forty-six dental implants, 6-mm long and 4.1-mm wide, were placed in the
posterior region in 20 patients. Patients were clinically and radiographically
examined after the restoration with single crowns and on a yearly basis.
Potential risk factors (arch, bruxism, maximum bite force, anatomical and
clinical C/I ratios, and occlusal table area) were analyzed according to the
following outcomes: implant survival, bone loss, and prosthetic complications.
RESULTS: The mean follow-up time was 45 +/- 9 (16-57) months. There was no early
loss of implants. After prosthetic loading, 4 implants were lost (2 in the
mandible and 2 in the maxilla; 91.3% survival), and there were 13 prosthetic
complications (28.3%), yielding a 65.2% success rate. The frailty term showed a
95% greater chance of loss in the mandible than the maxilla. Mean peri-implant
bone loss was of 0.2 +/- 0.4 mm, 0.1 +/- 0.2 mm, 0.1 +/- 0.3 mm, and 0.2 +/- 0.4
mm in the first, second, third, and fourth years, respectively, with a mean
cumulative loss of 0.3 +/- 0.5 mm at 48 months. In the multilevel model, the
effects of the clinical C/I ratio and time were significant for bone loss (P <
.001). It was estimated that a mean bone loss of 0.1 mm is associated with both a
one-unit increase in time (12 months) and a 0.1 increase in the clinical C/I
ratio. The other potential risk factors showed no significant relationship with
the outcomes. CONCLUSIONS: The 6-mm implants supporting single crowns performed
well, but the mandible shows a higher risk of failure. The time and clinical C/I
ratio are predictors for bone loss.
PMID- 28493385
TI - Effects of 25-hydroxycholecalciferol with two D3 vitamin levels on production and
immunity parameters in broiler chickens.
AB - This study was performed in Ross 308 chickens aged 1-21 days and aimed to
evaluate whether the addition of 25-hydroxycholecalciferol (25(OH)D3 ) to broiler
chicken diets affects their growth performance and immunity. A completely random
2 * 2 factorial arrangement was used with two levels of vitamin D3 and the
absence or presence of 25(OH)D3 , corresponding to four treatments based on
sorghum + soya bean diets: (i) 200 IU of vitamin D3 /kg of feed (Diet 1) (NRC, ),
(ii) Diet 1 + 69 MUg of 25(OH)D3 /kg of feed (Diet 2), (iii) 5,000 IU of vitamin
D3 /kg of feed (Diet 3) and (iv) Diet 3 + 69 MUg of 25(OH)D3 /kg of feed (Diet
4). Each treatment was conducted with six replicates of 10 chickens each. Water
and feed was supplied ad libitum. The results showed significantly increased
growth and tibia ash (p < .05) in the birds fed 5,000, IU of vitamin D3 /kg +
25(OH)D3 . Additionally, the cellular immune response increased significantly (p
< .05) in both treatments with added 25(OH)D3. Based on the results obtained
under the current test conditions, the addition of 25(OH)D3 at a rate of 69
MUg/kg to diets containing vitamin D3 improved the cellular immune response and
mineral deposition in the bones of broilers aged 1-21 days. Because these
parameters are very important in modern poultry farming, these results indicate
that supplementation with 25(OH)D3 should improve broiler production.
PMID- 28493386
TI - A Ferroelectric Ceramic/Polymer Composite-Based Capacitive Electrode Array for In
Vivo Recordings.
AB - A new implantable capacitive electrode array for electrocorticography signal
recording is developed with ferroelectric ceramic/polymer composite. This
ultrathin and electrically safe capacitive electrode array is capable of
attaching to the biological tissue conformably. The barium titanate/polyimide
(BaTiO3 /PI) nanocomposite with high dielectric constant is successfully
synthesized and employed as the ultrathin dielectric layer of the capacitive
BaTiO3 /PI electrode array. The performance of the capacitive BaTiO3 /PI
electrode array is evaluated by electrical characterization and 3D finite-element
modeling. In vivo, neural experiments on the visual cortex of rats show the
reliability of the capacitive BaTiO3 /PI electrode array. This work shows the
potentials of capacitive BaTiO3 /PI electrode array in the field of
brain/computer interfaces.
PMID- 28493387
TI - Current Advances in Highly Multiplexed Antibody-Based Single-Cell Proteomic
Measurements.
AB - Single-cell measurements have played a critical role in revealing the complex
signaling dynamics and heterogeneity present in cells, but there is still much to
learn. Measuring samples from bulk populations of cells often masks the
information and dynamics present in subsets of cells. Common single-cell protein
studies rely on fluorescent microscopy and flow cytometry but are limited in
multiplexing ability owing to spectral overlap. Recently, technology advancements
in single-cell proteomics have allowed highly multiplexed measurement of multiple
parameters simultaneously by using barcoded microfluidic enzyme-linked
immunosorbent assays and mass cytometry techniques. In this review, we will
describe recent work around multiparameter single-cell protein measurements and
critically analyze the techniques.
PMID- 28493389
TI - Contemporary transcatheter aortic valve replacement with third-generation balloon
expandable versus self-expanding devices.
AB - OBJECTIVES: To evaluate balloon-expandable and self-expanding third-generation
transcatheter aortic valve replacement (TAVR) devices according to patient
selection criteria and outcomes. BACKGROUND: Two competing third-generation TAVR
technologies are currently commercially available in the US. There are no
published head-to-head comparisons of the relative performance of these two
devices. METHODS: 257 consecutive patients undergoing TAVR with a third
generation balloon-expandable (Edwards Sapien 3) or self-expanding device
(Medtronic CoreValve Evolut R) at a single US medical center were included.
Choice of TAVR device was at the discretion of the multidisciplinary Heart Team.
Baseline clinical characteristics, echocardiographic and CT imaging, procedural
and 30-day outcomes were prospectively collected. RESULTS: 74 patients received a
self-expanding valve (SEV) and 183 received a balloon-expandable valve (BEV).
Patients selected for SEV were more frequently women, with lower body surface
area and smaller calcified iliofemoral arteries. Three SEV patients required
implantation of a second valve to successfully treat paravalvular leak. Only one
BEV patient had moderate paravalvular regurgitation. There was no difference in
the rate of stroke, major vascular complication or bleeding. Permanent pacemaker
implantation rate was significantly higher with SEV (12.7% vs 4.7%, P = 0.49) and
hospital length of stay was longer (8.3% vs 6.5%, P = 0.043), but 30-day
mortality was comparable (1.4% vs 1.6%, P = 1.00). CONCLUSIONS: Short-term
outcomes were equivalent between the two technologies. Clinically significant
paravalvular regurgitation was rare. SEV were more frequently selected in women
and patients with challenging transfemoral access, but were associated with
higher permanent pacemaker implantation rate and longer hospital length of stay.
PMID- 28493388
TI - Magnetic resonance elastography measured shear stiffness as a biomarker of
fibrosis in pediatric nonalcoholic fatty liver disease.
AB - : Magnetic resonance elastography (MRE) is a promising technique for noninvasive
assessment of fibrosis, a major determinant of outcome in nonalcoholic fatty
liver disease (NAFLD). However, data in children are limited. The purpose of this
study was to determine the accuracy of MRE for the detection of fibrosis and
advanced fibrosis in children with NAFLD and to assess agreement between manual
and novel automated reading methods. We performed a prospective, multicenter
study of two-dimensional (2D) MRE in children with NAFLD. MR elastograms were
analyzed manually at two reading centers, and using a new automated technique.
Analysis using each approach was done independently. Correlations were determined
between MRE analysis methods and fibrosis stage. Thresholds for classifying the
presence of fibrosis and of advanced fibrosis were computed and cross-validated.
In 90 children with a mean age of 13.1 +/- 2.4 years, median hepatic stiffness
was 2.35 kPa. Stiffness values derived by each reading center were strongly
correlated with each other (r = 0.83). All three analyses were significantly
correlated with fibrosis stage (center 1, rho = 0.53; center 2, rho = 0.55; and
automated analysis, rho = 0.52; P < 0.001). Overall cross-validated accuracy for
detecting any fibrosis was 72.2% for all methods (95% confidence interval [CI],
61.8%-81.1%). Overall cross-validated accuracy for assessing advanced fibrosis
was 88.9% (95% CI, 80.5%-94.5%) for center 1, 90.0% (95% CI, 81.9%-95.3%) for
center 2, and 86.7% (95% CI, 77.9%-92.9%) for automated analysis. CONCLUSION: 2D
MRE can estimate hepatic stiffness in children with NAFLD. Further refinement and
validation of automated analysis techniques will be an important step in
standardizing MRE. How to best integrate MRE into clinical protocols for the
assessment of NAFLD in children will require prospective evaluation. (Hepatology
2017;66:1474-1485).
PMID- 28493390
TI - Discrimination of a nerve fiber that is the origin of a cauda equina tumor using
acetylcholinesterase staining.
AB - Spinal nerve sheath tumors are well known to typically originate from dorsal
sensory nerve roots. However, it is difficult to anatomically identify the origin
in the case of cauda equina tumors. In this study, we aimed to ascertain whether
a cauda equina nerve root removed with a nerve sheath tumor was a motor nerve
using acetylcholinesterase (AchE) staining. Nerve rootlet sections removed with
tumors were stained for AchE using the AchE Rapid Staining Kit. Additionally, we
performed intraoperative motor-evoked potential (MEP) monitoring following either
transcranial electrical stimulation (TES) or electrical stimulation of nerve
rootlets. The muscular strength of the lower extremities was assessed bilaterally
before and after surgery using manual muscle testing. An AchE-positive motor
nerve rootlet that was the origin of a cauda equina tumor was observed in one of
the 12 patients. In this patient, a MEP in the right quadriceps evoked by
electrical stimulation of this rootlet was detected. TES-MEP showed a 30%
decrease in the amplitude in the right quadriceps evoked after tumor resection
with this nerve rootlet. However, the motor strength in both lower extremities
did not change after surgery. AchE staining and intraoperative MEP monitoring
could detect the motor nerve rootlet that was the origin of a cauda equina tumor.
Nerve sheath tumors originating from the motor nerve might be rare even in cauda
equina.
PMID- 28493391
TI - Haplotype reference consortium panel: Practical implications of imputations with
large reference panels.
AB - Recently, the Haplotype Reference Consortium (HRC) released a large imputation
panel that allows more accurate imputation of genetic variants. In this study, we
compared a set of directly assayed common and rare variants from an exome array
to imputed genotypes, that is, 1000 genomes project (1000GP) and HRC. We showed
that imputation using the HRC panel improved the concordance between assayed and
imputed genotypes at common, and especially, low-frequency variants. Furthermore,
we performed a genome-wide association meta-analysis of vertical cup-disc ratio,
a highly heritable endophenotype of glaucoma, in four cohorts using 1000GP and
HRC imputations. We compared the results of the meta-analysis using 1000GP to the
meta-analysis results using HRC. Overall, we found that using HRC imputation
significantly improved P values (P = 3.07 * 10-61 ), particularly for suggestive
variants. Both meta-analyses were performed in the same sample size, yet we found
eight genome-wide significant loci in the HRC-based meta-analysis versus seven
genome-wide significant loci in the 1000GP-based meta-analysis. This study
provides supporting evidence of the new avenues for gene discovery and fine
mapping that the HRC imputation panel offers.
PMID- 28493392
TI - Interventricular septal hematoma following repair of a ventricular septal defect.
AB - An interventricular septal hematoma is a rare complication after patch closure of
a ventricular septal defect (VSD). We describe three cases of interventricular
septal hematomas following patch VSD and discuss their management.
PMID- 28493393
TI - Final results of a European, multi-centre, prospective, observational Study of
PermacolTM collagen paste injection for the treatment of anal fistula.
AB - AIM: PermacolTM collagen paste (PermacolTM paste) is an acellular cross-linked
porcine dermal collagen matrix suspension for use in soft tissue repair. The use
of PermacolTM paste in the filling of anorectal fistula tract is a new sphincter
preserving method for fistula repair. The MASERATI100 study was a prospective,
observational clinical study with the objective to assess the efficacy of
PermacolTM collagen paste for anal fistula repair in 100 patients. METHOD:
Patients (N=100) with anal fistula were treated at ten European surgical sites
with a sphincter-preserving technique using PermacolTM paste. Fistula healing was
assessed at 1, 3, 6, and 12 months post-treatment, with the primary endpoint
being healing at 6 months. Faecal continence and patient satisfaction were
surveyed at each follow-up; adverse events (AEs) were monitored throughout the
follow-up. RESULTS: At 6 months post-surgery, 56.7% of patients were healed, and
the percentage healed was largely maintained, with 53.5% healed at 12 months.
29.0% of patients had at least one AE, and 16.0% of patients had one or more
procedure-related AE. Most AEs reported were minor and similar to those commonly
observed after fistula treatment, and the incidence of serious adverse events was
low (4.0% of patients). Regardless of treatment outcome, 73.0% of patients were
satisfied or very satisfied with the procedure. CONCLUSION: PermacolTM paste
provides a promising sphincter-preserving treatment for anal fistulas with
minimal adverse side-effects. This article is protected by copyright. All rights
reserved.
PMID- 28493394
TI - Determination of effective charges and ionic mobilities of polycationic
antimicrobial peptides by capillary isotachophoresis and capillary zone
electrophoresis.
AB - Capillary ITP (CITP) and CZE were applied to the determination of effective
charges and ionic mobilities of polycationic antimicrobial peptides (AMPs).
Twelve AMPs (deca- to hexadecapeptides) containing three to seven basic amino
acid residues (His, Lys, Arg) at variable positions of peptide chain were
investigated. Effective charges of the AMPs were determined from the lengths of
their ITP zones, ionic mobilities, and molar concentrations, and from the same
parameters of the reference compounds. Lengths of the ITP zones of AMPs and
reference compounds were obtained from their CITP analyses in cationic mode using
leading electrolyte (LE) composed of 10 mM NH4 OH, 40 mM AcOH (acetic acid), pH
4.1, and terminating electrolyte (TE) containing 40 mM AcOH, pH 3.2. Ionic
mobilities of AMPs and singly charged reference compounds (ammediol or arginine)
were determined by their CZE analyses in the BGE of the same composition as the
LE. The effective charges numbers of AMPs were found to be in the range 1.65
5.04, i.e. significantly reduced as compared to the theoretical charge numbers
(2.86-6.99) calculated from the acidity constants of the analyzed AMPs. This
reduction of effective charge due to tightly bound acetate counterions
(counterion condensation) was in the range 17-47% depending on the number and
type of the basic amino acid residues in the AMPs molecules. Ionic mobilities of
AMPs achieved values (26.5-38.6) * 10-9 m2 V-1 s-1 and in most cases were in a
good agreement with the ratio of their effective charges and relative molecular
masses.
PMID- 28493396
TI - Species sorting and stoichiometric plasticity control community C:P ratio of
first-order aquatic consumers.
AB - Ecological stoichiometry has proven to be invaluable for understanding consumer
response to changes in resource quality. Although interactions between trophic
levels occur at the community level, most studies focus on single consumer
species. In contrast to individual species, communities may deal with trophic
mismatch not only through elemental plasticity but also through changes in
species composition. Here, we show that a community of first-order consumers
(e.g. zooplankton) is able to adjust its stoichiometry (C:P) in response to
experimentally induced changes in resource quality, but only to a limited extent.
Furthermore, using the Price equation framework we show the importance of both
elemental plasticity and species sorting. These results illustrate the need for a
community perspective in ecological stoichiometry, requiring consideration of
species-specific elemental composition, intraspecific elemental plasticity and
species turnover.
PMID- 28493398
TI - Peer facilitation and burnout: the READ-SG pilot.
AB - BACKGROUND: Although there is much research about the prevalence of burnout among
doctors and postgraduate doctor trainees, there is a paucity of evidence for
effective preventive measures. METHODS: First-year postgraduate doctor trainees
(PGY1s) in Internal Medicine at our institution were given protected time to
participate in peer-facilitated monthly small group discussions on topics
regarding humanism and professional development. The authors prompted
participants before each session and followed a novel reflect, empathise, analyse
and discuss in small groups (READ-SG) format. During the pilot period the authors
administered a survey, approved by the Institutional Review Board, asking
participants to rank the perceived effect of the sessions on their professional
development and various symptoms of burnout, including levels of empathy, stress
and motivation. RESULTS: Out of 20 PGY1s available to attend each session over
the 3-month pilot period, there were an average of 9.6 attendees per session,
with a 100 per cent survey completion rate, yielding 29 surveys. A total of 21
survey responses (72.4%) reported speaking during the sessions, and 29 (100%)
reported that the sessions were important to have. Average scores on a Likert
scale from 1 to 5 (ranging from negative to positive, respectively) for the
perceived effect of the sessions on each measure were: 4.59 for professional
development; 4.38 for empathy; 4.00 for stress; and 4.28 for motivation. There is
a paucity of evidence for effective preventive measures [for burnout]
CONCLUSIONS: Peer-facilitated monthly small group discussions using the READ-SG
method seem to have positive effects on participants' sense of professional
development and symptoms of burnout among postgraduate doctor trainees.
PMID- 28493397
TI - A recurrent de novo mutation in ACTG1 causes isolated ocular coloboma.
AB - Ocular coloboma (OC) is a defect in optic fissure closure and is a common cause
of severe congenital visual impairment. Bilateral OC is primarily genetically
determined and shows marked locus heterogeneity. Whole-exome sequencing (WES) was
used to analyze 12 trios (child affected with OC and both unaffected parents).
This identified de novo mutations in 10 different genes in eight probands. Three
of these genes encoded proteins associated with actin cytoskeleton dynamics:
ACTG1, TWF1, and LCP1. Proband-only WES identified a second unrelated individual
with isolated OC carrying the same ACTG1 allele, encoding p.(Pro70Leu). Both
individuals have normal neurodevelopment with no extra-ocular signs of Baraitser
Winter syndrome. We found this mutant protein to be incapable of incorporation
into F-actin. The LCP1 and TWF1 variants each resulted in only minor disturbance
of actin interactions, and no further plausibly causative variants were
identified in these genes on resequencing 380 unrelated individuals with OC.
PMID- 28493399
TI - Diagnosis of fatty liver by computed tomography coronary artery calcium score.
AB - Nonalcoholic fatty liver disease may range from simple steatosis to fibrosis and
cirrhosis. It is associated with the development of coronary artery calcification
and appears to be an independent predictor of future adverse cardiovascular
events. As the presence of a fatty liver appears to portray an independent
increased risk, it may be beneficial to note this on coronary artery calcium
scoring reports. Determination of fatty liver is relatively easy to perform. We
discuss the method used by the Multi-Ethnic Study of Atherosclerosis (MESA) study
for determination of fatty liver from CT coronary artery calcium scoring
acquisitions, which may be implemented in clinical analysis.
PMID- 28493400
TI - Technoference: Parent Distraction With Technology and Associations With Child
Behavior Problems.
AB - Heavy parent digital technology use has been associated with suboptimal parent
child interactions, but no studies examine associations with child behavior. This
study investigates whether parental problematic technology use is associated with
technology-based interruptions in parent-child interactions, termed
"technoference," and whether technoference is associated with child behavior
problems. Parent reports from 170 U.S. families (child Mage = 3.04 years) and
actor-partner interdependence modeling showed that maternal and paternal
problematic digital technology use predicted greater technoference in mother
child and father-child interactions; then, maternal technoference predicted both
mothers' and fathers' reports of child externalizing and internalizing behaviors.
Results suggest that technological interruptions are associated with child
problem behaviors, but directionality and transactional processes should be
examined in future longitudinal studies.
PMID- 28493401
TI - The effect of adjuvant chemotherapy on survival and recurrence after curative
rectal cancer surgery in patients who are histologically node negative after
neoadjuvant chemoradiotherapy.
AB - AIM: The aim of this study was to evaluate whether adjuvant chemotherapy will
affect recurrence rate or disease-free and overall survival in patients with
rectal adenocarcinoma who were staged with MRI node-positive disease (mrN+)
preoperatively. These patients underwent neoadjuvant chemoradiotherapy with
curative rectal cancer surgery and their pathological staging was negative for
nodal disease (ypN0). There is no consensus on the role of adjuvant chemotherapy
in such patients. METHOD: Patients who received neoadjuvant chemoradiotherapy and
underwent curative rectal cancer surgery for rectal adenocarcinoma staged as
[mrTxN+M0] on MRI staging and who on pathological staging were found to be
[ypTxN0M0] were retrospectively identified from January 2008 December 2012 from
two tertiary referral centres (Royal Marsden Hospital, London and Saint-Andre
Hospital, Bordeaux). RESULTS: One hundred and sixty-three patients were recruited
and, after propensity matching at a ratio of 2:1, n = 80 patients were divided to
receive adjuvant (n = 28) or no adjuvant treatment (n = 52). A comparison of
adjuvant chemotherapy vs no adjuvant therapy showed that the mean overall
survival was 2.67 vs 3.60 years (P = 0.42) and disease-free survival was 2.27 vs
3.32 years (P = 0.14). CONCLUSION: This study found no significant difference in
survival or disease recurrence between patients who received adjuvant
chemotherapy and patients who did not. There is no clear evidence to support or
dismiss the use of adjuvant chemotherapy for patients who were node positive on
preoperative MRI and node negative on histopathological staging. Further
multicentre prospective randomized trials are needed to identify the appropriate
treatment regime for this group of patients.
PMID- 28493403
TI - Suicide prevention in mental health services: A qualitative analysis of coroners'
reports.
AB - Suicide is a major concern for mental health nurses because of its clear
correlation with mental illness. In New Zealand, coroners investigate all deaths
that appear to be a result of suicide, and provide reports to mental health
services (MHS). The aim of the present study was to investigate coronial
recommendations to MHS in relation to suicide prevention and to examine clinical
and family responses to these. The present study was a three-phase design: (i)
analysis of coroners' recommendations related to suicide in MHS; (ii) interviews
with clinicians for their response to the recommendations; and (iii) interviews
with individuals working with families of consumers of MHS for their responses in
relation to family-related recommendations. A qualitative content analysis was
conducted on the recommendations from coroners, the interviews with clinical
leaders, and the focus group for family workers. Coroners recommended that MHS
should implement suicide-prevention strategies that would facilitate improved
communication, risk containment, service delivery, and family involvement.
Clinicians agreed with most recommendations, apart from those related to risk
containment. Family workers endorsed the coronial perspective that family
inclusion in MHS was suboptimal. Coroners, MHS, and mental health nurses need to
consider the latest clinical evidence for suicide prevention. However, given the
complexity of factors that influence suicide, it is important to be realistic
about MHS role in preventing suicide, but ensure that MHS provide interventions
for which there is evidence, including facilitating family participation and
providing access to psychotherapies.
PMID- 28493402
TI - Development and validation of HPLC-MS/MS method for the determination of
lixivaptan in mouse plasma and its application in a pharmacokinetic study.
AB - The aim of the present study was to develop a simple, sensitive and accurate
liquid chromatography-electrospray ionization tandem mass spectrometry (ESI
MS/MS) method for the determination of lixivaptan (LIX) in mouse plasma using
vildagliptin as the internal standard (IS). A precipitation procedure was used
for the extraction of LIX and vildagliptin from mouse plasma. Chromatographic
separation of LIX was achieved using a C18 analytical column (50 * 2.1 mm, 1.8
MUm) at 25 degrees C. The mobile phase comprised acetonitrile and ammonium
formate (10 mm, pH 3.1; 40:60, v/v) pumped at a flow rate of 0.3 mL min-1 . A
tandem mass spectrometer with an electrospray ionization source was used to
perform the assay. Quantification of LIX at m/z 290 -> 137 and IS at 154 -> 97
was attained through multiple reaction monitoring. The investigated method was
authenticated following the bio-analytical method of validation guidelines of the
US Food and Drug Administration. The developed method showed a good linearity
over the concentration range from 5 to 500 ng mL-1 , and the calibration curve
was linear (r = 0.9998). The mean recovery of LIX from mouse plasma was 99.2 +/-
0.68%. All validation parameters for LIX were within the levels required for
acceptance. The proposed method was effectively used for a pharmacokinetic study
of LIX in mouse plasma.
PMID- 28493404
TI - Accuracy of finite-difference harmonic frequencies in density functional theory.
AB - Analytic Hessians are often viewed as essential for the calculation of accurate
harmonic frequencies, but the implementation of analytic second derivatives is
nontrivial and solution of the requisite coupled-perturbed equations engenders a
sizable memory footprint for large systems, given that these equations are not
required for energy and gradient calculations in density functional theory. Here,
we benchmark the alternative approach to harmonic frequencies based on finite
differences of analytic first derivatives, a procedure that is amenable to large
scale parallelization. Not only for absolute frequencies but also for isotopic
and conformer-dependent frequency shifts in flexible molecules, we find that the
finite-difference approach exhibits mean errors < 0.1 cm-1 as compared to results
based on an analytic Hessian. For very small frequencies corresponding to
nonbonded vibrations in noncovalent complexes (for which the harmonic
approximation is questionable anyway), the finite-difference error can be larger,
but even in these cases the errors can be reduced below 0.1 cm-1 by judicious
choice of the displacement step size and a higher-order finite-difference
approach. The surprising accuracy and robustness of the finite-difference results
suggests that availability of the analytic Hessian is not so important in today's
era of commodity processors that are readily available in large numbers. (c) 2017
Wiley Periodicals, Inc.
PMID- 28493405
TI - Australian urban Indigenous smokers' perspectives on nicotine products and
tobacco harm reduction.
AB - INTRODUCTION AND AIMS: Indigenous Australians experience a significant gap in
life expectancy compared with non-Indigenous Australians. Indigenous communities
have high-smoking prevalence and low engagement with cessation therapies. This
qualitative research, conducted in an urban Australian Indigenous community,
explored smokers' views on smoking, quitting and engagement with current nicotine
replacement therapies. Opinions on acceptability of tobacco harm reduction were
sought. We explored the acceptability of novel nicotine products, that is, new or
unfamiliar products, including non-therapeutic options, such as e-cigarettes.
DESIGN AND METHODS: Focus groups and individual interviews with adult Indigenous
daily smokers (n = 27) were used. Current and novel nicotine products were
displayed and demonstrated. Discussions were audio-recorded, transcribed and
analysed thematically. RESULTS: Participants expressed interest in trying
existing and novel nicotine products. Short-to-medium term use of nicotine
replacement therapy for quitting was generally acceptable; views on long-term use
were mixed. Interest in use of tobacco substitutes depended on their perceived
effectiveness, providing a 'kick' and 'relieving stress'. Desirable qualities for
tobacco substitutes were identified with gender differences and product
preferences noted. The unpleasant taste of existing products is a barrier to both
short-term and long-term use. DISCUSSION: We found substantial interest in trying
some existing and novel nicotine products, mostly for short-term use. A number of
attributes were identified that would make nicotine products potentially
acceptable as a long-term substitute. CONCLUSIONS: Some participants were
interested in long-term substitution if acceptable products were available.
Improvements in current products and access to novel products are needed if
tobacco harm reduction is to be acceptable. [Yuke K, Ford P, Foley W, Mutch A,
Fitzgerald L, Gartner C. Australian urban Indigenous smokers' perspectives on
nicotine products and tobacco harm reduction. Drug Alcohol Rev 2018;37:87-96].
PMID- 28493407
TI - First-person perspective video to enhance simulation.
AB - BACKGROUND: Simulation training is increasingly being used as part of the
undergraduate medical curriculum, but it remains time and faculty member
intensive. To improve efficacy, videos have been used prior to the simulation of
practical procedures; however, using videos prior to simulation training
concerning the management of patients who are unwell has not been investigated.
The aim of this project was to see whether clinical decision-making and non
technical skills can be improved if a video is used prior to simulation training,
and uniquely to enhance the authenticity we filmed it using a first-person
perspective. METHODOLOGY: We conducted a randomised controlled trial with 40
final-year medical students randomised into two groups. One group viewed a video
filmed in first person prior to a simulation scenario, whereas the other group
did not view the video. The two groups then carried out the simulation and were
assessed with 'time to' investigation and treatment decisions. Further
quantitative data were collected for non-technical skills using the Ottawa Crisis
Resource Management (OCRM) score. Qualitative data were collected from the
students as to the perceived ease of use and helpfulness of the video. Simulation
training is increasingly being used as part of the undergraduate medical
curriculum RESULTS: The students who watched the video appeared to perform better
in clinical decision-making and non-technical skills. The students were extremely
receptive to the use of a first-person perspective video, and highlighted its
perceived realism and its help as a memory aid. DISCUSSION: The use of this style
of video was warmly received by students and opens the possibility of further use
to enhance simulation training.
PMID- 28493408
TI - Monoubiquitination joins polyubiquitination as an esteemed proteasomal targeting
signal.
AB - A polyubiquitin chain attached covalently to the target substrate has been
recognized for long as the "canonical" proteasomal degradation signal. However,
several proteins have been shown to be targeted for degradation following
monoubiquitination, indicating that the proteasome can recognize signals other
than a ubiquitin polymer. A comprehensive screen aiming at determining the extent
of this mode of recognition revealed that ~40% of mammalian and ~20% of yeast
proteins are degraded following monoubiquitination. Characterization of these
proteins showed that on average, the monoubiquitinated proteins are smaller than
the polyubiquitinated ones, and in humans, are less disordered. Further, proteins
degraded by the two different modes belong to distinct functional groups. These
findings along with detailed structural analysis of the proteasome, its ubiquitin
receptors and deubiquitinating enzymes, suggest that the ubiquitin signal - its
formation, recognition, editing, and removal - is far more complex and diverse
than originally assumed. Also see the video abstract here:
https://youtu.be/QKpN9c6Rg20.
PMID- 28493406
TI - Beta-hydroxy-beta-methylbutyrate supplementation and skeletal muscle in healthy
and muscle-wasting conditions.
AB - Beta-hydroxy-beta-methylbutyrate (HMB) is a metabolite of the essential amino
acid leucine that has been reported to have anabolic effects on protein
metabolism. The aims of this article were to summarize the results of studies of
the effects of HMB on skeletal muscle and to examine the evidence for the
rationale to use HMB as a nutritional supplement to exert beneficial effects on
muscle mass and function in various conditions of health and disease. The data
presented here indicate that the beneficial effects of HMB have been well
characterized in strength-power and endurance exercise. HMB attenuates exercise
induced muscle damage and enhances muscle hypertrophy and strength, aerobic
performance, resistance to fatigue, and regenerative capacity. HMB is
particularly effective in untrained individuals who are exposed to strenuous
exercise and in trained individuals who are exposed to periods of high physical
stress. The low effectiveness of HMB in strength-trained athletes could be due to
the suppression of the proteolysis that is induced by the adaptation to training,
which may blunt the effects of HMB. Studies performed with older people have
demonstrated that HMB can attenuate the development of sarcopenia in elderly
subjects and that the optimal effects of HMB on muscle growth and strength occur
when it is combined with exercise. Studies performed under in vitro conditions
and in various animal models suggest that HMB may be effective in treatment of
muscle wasting in various forms of cachexia. However, there are few clinical
reports of the effects of HMB on muscle wasting in cachexia; in addition, most of
these studies evaluated the therapeutic potential of combinations of various
agents. Therefore, it has not been possible to determine whether HMB was
effective or if there was a synergistic effect. Although most of the endogenous
HMB is produced in the liver, there are no reports regarding the levels and the
effects of HMB supplementation in subjects with liver disease. Several studies
have suggested that anabolic effects of HMB supplementation on skeletal muscle do
not occur in healthy, non-exercising subjects. It is concluded that (i) HMB may
be applied to enhance increases in the mass and strength of skeletal muscles in
subjects who exercise and in the elderly and (ii) studies examining the effects
of HMB administered alone are needed to obtain conclusions regarding the specific
effectiveness in attenuating muscle wasting in various muscle-wasting disorders.
PMID- 28493409
TI - Unruptured sinus of Valsalva aneurysm mimicking as right atrial tumor.
AB - Sinus of Valsalva aneurysm is a rare congenital cardiac abnormality and is
usually diagnosed when it ruptures. An asymptomatic 55-year-old male of
unruptured sinus of Valsalva aneurysm of noncoronary cusp was on medical follow
up. At 2-year follow-up, there was thrombus formation in the aneurysm, mimicking
right atrium tumor on 2D transthoracic echocardiography. Cardiac computed
tomography showed filling defect in the aneurysm suggestive of thrombus.
Considering the high risk of systemic emboli surgery was performed, and aneurysm
was repaired with Dacron patch.
PMID- 28493410
TI - Expression and prognostic significance of programmed death protein 1 and
programmed death ligand-1, and cytotoxic T lymphocyte-associated molecule-4 in
hepatocellular carcinoma.
AB - Hepatocellular carcinoma (HCC) is one of the most common malignancies and causes
of death worldwide. In this study, we assessed the correlation between
clinicopathologic factors with programmed cell death protein 1 (PD-1) and
programmed cell death ligand-1 (PD-L1), and cytotoxic T lymphocyte-associated
molecule-4 (CTLA-4) expressions. Furthermore, we analyzed the prognostic
significance of these proteins in a subgroup of patients. We retrospectively
evaluated the PD-1, PD-L1, and CTLA-4 expressions in 294 HCC tissue microarray
samples using immunohistochemistry. PD-1 and PD-L1 expressions were significant
related to high CD8+ tumor-infiltrating lymphocytes (TILs) (r = 0.664, p < 0.001
and r = 0.149, p = 0.012). Only high Edmondson-Steiner grade was statistically
related to high PD-1 expression. High PD-L1 expression was demonstrated as an
independent poor prognostic factor for disease-free survival in addition to
previous known factors, size >5 cm and serum albumin <=3.5 g/dL in high CD8+ TILs
group. We have demonstrated that the combined high expression of PD-L1 and CD8+
TIL is an important prognostic factor related to the immune checkpoint pathway in
HCC and furthermore, there is a possibility that it could be used as a predictor
of therapeutic response. Also, this result would be helpful in evaluating the
applicable group of PD-1/PD-L1 blocking agent for HCC patients.
PMID- 28493411
TI - Insulinaemia and insulin resistance in Caucasian general paediatric population
aged 2 to 10 years: Associated risk factors.
AB - BACKGROUND: The aim of this study is to determine values of insulinaemia,
homeostasis model assessment (HOMA) index and quantitative insulin sensitivity
check index (QUICKI) among a population of prepubertal Caucasian children, to
analyse factors associated with insulin resistance (IR), and to study its
association with cardiovascular risk factors. MATERIALS AND METHODS: Population
based study conducted on a randomly selected sample of prepubescent Caucasian
subjects aged 2.00 to 9.99 years old. Anthropometric measurements, blood
pressure, and fasting blood samples were obtained, including fasting glucose,
triglycerides, High Density Lipoprotein (HDL)-cholesterol, and insulin. In
addition, QUICKI and HOMA indices were calculated. Generalised additive models
for location, scale and shape (GAMLSS) was used to calculate centiles curves and
multivariate logistic regression analysis to assess factors associated with IR.
RESULTS: A total of 654 subjects were included. Mean values obtained for
insulinaemia, HOMA index, and QUICKI were 3.74 MUIU/mL, 0.73, and 0.44,
respectively, in the overall population and 3.32 MUIU/mL, 0.64 and 0.46,
respectively, in normal weight subjects. The main factor associated with IR was
abdominal obesity (odds ratio [OR] 3.38 [95% CI 1.44-7.94] in the subgroup aged
2.00-5.99 years and OR 9.14 [3.42-24.41] for those aged 6.00-9.99 years). An
increased risk of hyperglycaemia (P = 0.043), hypertriglyceridaemia (P < .001),
and HDL < p10 (P = 0.021) was described among children aged 2.00 to 5.99 years
with IR, and among those aged 6.00 to 9.99 years, IR was associated with an
increased risk of hypertriglyceridaemia (P < .001). CONCLUSION: Abdominal obesity
was the main factor associated with IR. Metabolic changes associated with IR seem
to be present from early stages of life, which highlights the importance of the
prevention, early diagnosis and treatment of obesity.
PMID- 28493413
TI - Examining the emerging entrepreneurial mindset in adolescence: A study in
Nigeria.
AB - This study investigated the relationship of family environment, network, parental
socio-economic status, self-efficacy and proactive personality on entrepreneurial
intention of secondary school adolescents and the mediating role of self
efficacy. The participants were 250 secondary school SS2 adolescents randomly
selected from six secondary schools in Ibadan Metropolis, Ibadan, Oyo State,
Nigeria. Structural Equation Modelling was used to analyse the data obtained from
the participants. The results showed that all the contextual and individual
factors had significant relationship with entrepreneurial intention and self
efficacy partially mediated the relationship. It was suggested that counselling
psychologists should consider the contextual and individual variables while
assisting students in building their entrepreneurial intention.
PMID- 28493412
TI - Reassessment of alkaline phosphatase as serum tumor marker with high specificity
in osteosarcoma.
AB - The goal of this study was to reassess serum alkaline phosphatase (ALP) as tumor
marker in osteosarcoma. We retrospectively examined serum ALP levels at
diagnosis, every therapeutic step (neoadjuvant chemotherapy, surgery, and
adjuvant chemotherapy), metastasis, and follow-up and analyzed the role of ALP as
tumor marker in 210 osteosarcomas. The diagnostic performances of ALP were
validated with pathology-proven 899 other primary bone lesions. Elevated ALP at
diagnosis was associated with inferior overall survival (OS) (Log Rank P < 0.001)
and disease-free survival (Log Rank P = 0.005) and independently significant for
OS in multivariate analysis (hazard ratio [HR]=2.12, P = 0.032). During therapy,
the ALP level significantly changed according to therapeutic steps (P < 0.001 for
patients >=15 years old, P < 0.001 for patients <15 years old) and survival (P =
0.015 for >=15 years, P = 0.002 for <15 years), and the response of ALP to
therapy and survival were associated (P = 0.042 for >=15 years, P = 0.036 for <15
years). Initial ALP level was linearly correlated with tumor burden (total tumor
volume; P = 0.016 for >=15 years, bone tumor volume; P = 0.012 for >=15 years).
The sensitivity and specificity of ALP on diagnosis were 53.2% (95% Confidence
Interval [CI]: 0.475-0.586) and 90.1% (95% CI: 0.888-0.913). The sensitivity of
ALP on metastasis was 53.2% (95% CI: 0.431-0.624), and the specificity was 78.2%
(95% CI: 0.720-0.839) at15 months postoperative and 90.0% (95% CI: 0.824-0.952)
at 3 years postoperative. Serum ALP was found to be a valuable tumor marker with
high specificity in osteosarcoma.
PMID- 28493414
TI - Investigating niche partitioning of ectomycorrhizal fungi in specialized rooting
zones of the monodominant leguminous tree Dicymbe corymbosa.
AB - Temperate ectomycorrhizal (ECM) fungi show segregation whereby some species
dominate in organic layers and others favor mineral soils. Weak layering in
tropical soils is hypothesized to decrease niche space and therefore reduce the
diversity of ectomycorrhizal fungi. The Neotropical ECM tree Dicymbe corymbosa
forms monodominant stands and has a distinct physiognomy with vertical crown
development, adventitious roots and massive root mounds, leading to multi-stemmed
trees with spatially segregated rooting environments: aerial litter caches,
aerial decayed wood, organic root mounds and mineral soil. We hypothesized that
these microhabitats host distinct fungal assemblages and therefore promote
diversity. To test our hypothesis, we sampled D. corymbosa ectomycorrhizal root
tips from the four microhabitats and analyzed community composition based on
pyrosequencing of fungal internal transcribed spacer (ITS) barcode markers.
Several dominant fungi were ubiquitous but analyses nonetheless suggested that
communities in mineral soil samples were statistically distinct from communities
in organic microhabitats. These data indicate that distinctive rooting zones of
D. corymbosa contribute to spatial segregation of the fungal community and likely
enhance fungal diversity.
PMID- 28493416
TI - Parathyroidectomy for the treatment of hyperparathyroidism: Thirty-day morbidity
and mortality.
AB - OBJECTIVES/HYPOTHESIS: Evaluate morbidity and mortality rates for patients with
different levels of hyperparathyroidism (HPT) undergoing parathyroidectomy (PTX),
specifically comparing primary hyperparathyroidism to secondary and tertiary
hyperparathyroidism. Assess predictive factors of increased morbidity and
mortality. STUDY DESIGN: Retrospective national database review. METHODS:
Patients undergoing PTX, defined by Current Procedural Terminology codes 60500,
60502, 60505, for the treatment of HPT, were identified in the American College
of Surgeons National Surgical Quality Improvement Program database between 2006
and 2014. Incidence of morbidity and mortality was calculated for primary,
secondary, and tertiary HPT. A t test, analysis of variance, and chi2 analyses
were used to assess preoperative characteristics among the three groups. RESULTS:
A total of 21,267 patients were included in the analysis. There was an overall
7.2% morbidity and mortality rate, including 45 (0.21%) deaths, a 1.8%
readmission rate, and a 1.9% reoperation rate, but morbidity and mortality rates
were widely divergent when comparing primary to secondary and tertiary HPT. PTX
resulted in a 4.9% morbidity and mortality rate for primary HPT (n = 14,500),
26.8% morbidity and mortality rate for secondary HPT (n = 1661), and 21.8%
morbidity and mortality rate for tertiary HPT (n = 588). The primary reason for
readmission was hypocalcemia (18.3%). Hematoma (7.2%) and postoperative
hemorrhage (3.3%) were the two most common causes of reoperation. Elevated
preoperative serum creatinine, alkaline phosphatase, and hypertension resulted in
a higher rate of complications after PTX (P < .0001). CONCLUSIONS: Although
surgery for primary HPT is an extremely common and safe procedure with minimal
morbidity and mortality rates, PTX for secondary and tertiary HPT has
significantly higher rates of morbidity and mortality, requiring special
attention in the postoperative period. Predictive factors of poor outcomes
include hypertension, elevated creatinine, and elevated alkaline phosphatase.
LEVEL OF EVIDENCE: 4. Laryngoscope, 128:528-533, 2018.
PMID- 28493417
TI - Retroesophageal course of left brachiocephalic vein: The garland vein.
PMID- 28493420
TI - Comment on: "Comprehensive first-line magnetic resonance imaging in hypertension:
experience from a single-center tertiary referral clinic".
PMID- 28493418
TI - Muscle mass and association to quality of life in non-small cell lung cancer
patients.
AB - BACKGROUND: Cancer wasting is characterized by muscle loss and may contribute to
fatigue and poor quality of life (QoL). Our aim was to investigate associations
between skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD) and
selected QoL outcomes in advanced non-small cell lung cancer (NSCLC) at
diagnosis. METHODS: Baseline data from patients with stage IIIB/IV NSCLC and
performance status 0-2 enrolled in three randomized trials of first-line
chemotherapy (n = 1305) were analysed. Associations between SMI (cm2 /m2 ) and
SMD (Hounsfield units) based on computed tomography-images at the third lumbar
level and self-reported physical function (PF), role function (RF), global QoL,
fatigue, and dyspnoea were investigated by linear regression using flexible non
linear modelling. RESULTS: Complete data were available for 734 patients, mean
age 65 years. Mean SMI was 47.7 cm2 /m2 in men (n = 420) and 39.6 cm2 /m2 in
women (n = 314). Low SMI values were non-linearly associated with low PF and RF
(men P = 0.016/0.020, women P = 0.004/0.012) and with low global QoL (P = 0.001)
in men. Low SMI was significantly associated with high fatigue (P = 0.002) and
more pain (P = 0.015), in both genders, but not with dyspnoea. All regression
analyses showed poorer physical outcomes below an SMI breakpoint of about 42-45
cm2 /m2 for men and 37-40 cm2 /m2 for women. In both genders, poor PF and more
dyspnoea were significantly associated with low SMD. CONCLUSIONS: Low muscle mass
in NSCLC negatively affects the patients' PF, RF, and global QoL, possibly more
so in men than in women. However, muscle mass must be below a threshold value
before this effect can be detected.
PMID- 28493419
TI - Support for alcohol policies from drinkers in the City of Tshwane, South Africa:
Data from the International Alcohol Control study.
AB - INTRODUCTION AND AIMS: South Africa is considering a range of alcohol policy
reforms. This study aims to determine the magnitude of public support for 13
alcohol policies in the Tshwane Metropolitan Municipality and whether this varies
by demographic factors and heavy drinking status. DESIGN AND METHODS: Data are
from the South African arm of the International Alcohol Control study, a
household survey of adult drinkers using a multistage stratified cluster random
sampling design. The sample included 1920 drinkers aged 18-65 years (62% men),
with complete drinking data for 16 drinking locations on 955 persons (510 heavy
and 445 not heavy drinkers). RESULTS: Over half (53%) of the sample were found to
be heavy drinkers. Support varied by alcohol policy, ranging from 31% to 77%,
with support above 50% for 11 of the 13 policies. Policy support was higher for
policies increasing the purchase age to 21 years (77%), addressing drink driving
(58-76%) and restricting physical availability (60-66%). There was slightly less
support for policies restricting alcohol marketing (59%) or for policies
increasing the price of alcohol (34-58%), especially if no justification was
given or the funds were not earmarked. Policy support differed by age, gender,
heavy drinking status and income. DISCUSSION AND CONCLUSIONS: Public support from
adult drinkers for a range of alcohol policies is extensive and, as found
elsewhere, was strongest for raising the minimum drinking age and lowest for
increasing prices. The support from drinkers to increasing controls on alcohol
could be one lever to getting control measures implemented. [Parry CDH,
Trangenstein P, Lombard C, Jernigan DH, Morojele NK. Support for alcohol policies
from drinkers in the City of Tshwane, South Africa: Data from the International
Alcohol Control study. Drug Alcohol Rev 2017;00:000-000].
PMID- 28493421
TI - Quantitative proteomics in plant protease substrate identification.
AB - Contents Summary 936 I. Introduction 936 II. The quest for plant protease
substrates - proteomics to the rescue? 937 III. Quantitative proteome comparison
reveals candidate substrates 938 IV. Dynamic metabolic stable isotope labeling to
measure protein turnover in vivo 938 V. Terminomics - large-scale identification
of protease cleavage sites 939 VI. Substrate or not substrate, that is the
question 940 VII. Concluding remarks 941 Acknowledgements 941 References 941
SUMMARY: Proteolysis is a central regulatory mechanism of protein homeostasis and
protein function that affects all aspects of plant life. Higher plants encode for
hundreds of proteases, but their physiological substrates and hence their
molecular functions remain mostly unknown. Current quantitative mass spectrometry
based proteomics enables unbiased large-scale interrogation of the proteome and
its modifications. Here we provide an overview of proteomics techniques that
allow profiling of changes in protein abundance, measurement of proteome turnover
rates, identification of protease cleavage sites in vivo and in vitro and
determination of protease sequence specificity. We discuss how these techniques
can help to reveal protease substrates and determine plant protease function,
illustrated by recent studies on selected plant proteases.
PMID- 28493423
TI - Development and validation of a sensitive UHPLC-MS/MS method for quantitative
analysis of farrerol in rat plasma: Application to pharmacokinetic and
bioavailability studies.
AB - Farrerol is a 2,3-dihydro-flavonoid isolated from rhododendron. In this study, a
sensitive and selective ultra-high performance liquid chromatography-tandem mass
spectrometry (UHPLC-MS/MS) method was developed for the determination of farrerol
in rat plasma. Liquid-liquid extraction by ethyl ether was used for sample
preparation. Chromatographic separation was achieved on an Agilent UHPLC XDB-C18
column (2.1 * 100 mm, 1.8 MUm) with water and methanol (30:70, v/v) as the mobile
phase. An electrospray source was applied and operated in negative ion mode;
selection reaction monitoring was used for quantification using target fragment
ions m/z 299 -> 179 for farrerol and m/z 267 -> 252 for internal standard.
Calibration plots were linear in the range of 2.88-1440 ng/mL for farrerol in rat
plasma. Intra- and inter-day precisions were <11.6%, and the accuracy ranged from
-13.9 to 11.9%. The UHPLC-MS/MS method was successfully applied in
pharmacokinetics and bioavailability studies of farrerol in rats.
PMID- 28493422
TI - Differences in presentation, progression and rates of arthroplasty between hip
and knee osteoarthritis: Observations from an osteoarthritis cohort study-a clear
role for conservative management.
AB - AIM: To describe the natural progression and the rates of arthroplasty of a
cohort of hip and knee osteoarthritis (OA) patients. METHODS: An observational
study of 247 consecutive patients who attended an OA clinic between May 2008 and
August 2009. Follow-up survey was conducted from July 2014 to December 2014, with
the primary end point being joint replacement surgery. RESULTS: One hundred and
sixty-seven patients had knee OA and 80 patients had hip OA. When adjusted for
other variables (age, gender, body mass index, Kellgren-Lawrence stage, symptom
duration, presence of OA elsewhere and pain score), patients with hip OA
demonstrated 86% increased hazard of surgery compared to knee OA patients (95% CI
increase of 19% to 193%). At 6 years after initial consultation, 67% of patients
with knee OA did not require a knee replacement surgery, while 40% (30, 51) of
hip OA patients did not undergo surgery (95% CI: 59-74%). Overall at 6 years, 58%
of patients (95% CI: 51-64%) did not undergo joint replacement surgery.
CONCLUSION: Knee and hip OA patients appear to behave differently, with hip OA
patients more likely to undergo arthroplasty. There is a significant number of
both hip OA and knee OA patients who did not require arthroplasty at the end of 6
years, suggesting a major role for conservative therapy.
PMID- 28493424
TI - The Dynamic Multisite Interactions between Two Intrinsically Disordered Proteins.
AB - Protein interactions involving intrinsically disordered proteins (IDPs) comprise
a variety of binding modes, from the well-characterized folding upon binding to
dynamic fuzzy complexes. To date, most studies concern the binding of an IDP to a
structured protein, while the interaction between two IDPs is poorly understood.
In this study, NMR, smFRET, and molecular dynamics (MD) simulation are combined
to characterize the interaction between two IDPs, the C-terminal domain (CTD) of
protein 4.1G and the nuclear mitotic apparatus (NuMA) protein. It is revealed
that CTD and NuMA form a fuzzy complex with remaining structural disorder.
Multiple binding sites on both proteins were identified by molecular dynamics and
mutagenesis studies. This study provides an atomic scenario in which two IDPs
bearing multiple binding sites interact with each other in dynamic equilibrium.
The combined approach employed here could be widely applicable for investigating
IDPs and their dynamic interactions.
PMID- 28493425
TI - Law enforcement-derived data on gabapentin diversion and misuse, 2002-2015:
diversion rates and qualitative research findings.
AB - PURPOSE: Recent limited epidemiologic and case reports suggest that gabapentin is
being misused, especially among prescription opioid misusers. However, no
apparent studies have reported data from law enforcement on the diversion and
misuse of gabapentin. METHODS: Case report data are drawn from a quarterly survey
of prescription drug diversion completed by a national sample of law enforcement
and regulatory agencies who engage in drug diversion investigations. Rates of
gabapentin diversion per 100 000 population were calculated for each quarter from
2002 through 2015. Qualitative data are drawn from a brief questionnaire
completed by a subsample of survey respondents and were organized and presented
by theme. RESULTS: In total, 407 new cases of diverted gabapentin were reported
during the time period, with diversion rates steadily increasing from zero cases
in the first 2 quarters of 2002 to a high of 0.027 cases per 100 000 population
in the fourth quarter of 2015. Qualitative data suggest that gabapentin is being
misused in conjunction with prescription opioids and that gabapentin and heroin
are being combined and consumed together. Law enforcement reporters found these
drug use trends to be contributing to gabapentin diversion. CONCLUSIONS: The
recent increase in gabapentin diversion appears to be related to the opioid
epidemic, based on law enforcement descriptions of gabapentin being misused in
combination with opioids. Yet epidemiological data related to this finding is
limited and research conducted among gabapentin misusers is needed to understand
this problem in more depth. Greater monitoring of gabapentin abuse and diversion
appear warranted.
PMID- 28493426
TI - Optical coherence elastography for strain dynamics measurements in laser
correction of cornea shape.
AB - We describe the use of elastographic processing in phase-sensitive optical
coherence tomography (OCT) for visualizing dynamics of strain and tissue-shape
changes during laser-induced photothermal corneal reshaping, for applications in
the emerging field of non-destructive and non-ablative (non-LASIK) laser vision
correction. The proposed phase-processing approach based on fairly sparse data
acquisition enabled rapid data processing and near-real-time visualization of
dynamic strains. The approach avoids conventional phase unwrapping, yet allows
for mapping strains even for significantly supra-wavelength inter-frame
displacements of scatterers accompanied by multiple phase-wrapping. These
developments bode well for real-time feedback systems for controlling the
dynamics of corneal deformation with 10-100 ms temporal resolution, and for
suitably long-term monitoring of resultant reshaping of the cornea. In ex-vivo
experiments with excised rabbit eyes, we demonstrate temporal plastification of
cornea that allows shape changes relevant for vision-correction applications
without affecting its transparency. We demonstrate OCT's ability to detect
achieving of threshold temperatures required for tissue plastification and
simultaneously characterize transient and cumulative strain distributions,
surface displacements, and scattering tissue properties. Comparison with
previously used methods for studying laser-induced reshaping of cartilaginous
tissues and numerical simulations is performed.
PMID- 28493427
TI - DNA Identification of Commingled Human Remains from the Cemetery Relocated by
Flooding in Central Bosnia and Herzegovina.
AB - The floods in Bosnia and Herzegovina in May 2014 caused landslides all over the
country. In the small village of Serici, near the town of Zenica, a landslide
destroyed the local cemetery, relocated graves, and commingled skeletal remains.
As the use of other physical methods of identification (facial recognition,
fingerprint analysis, dental analysis, etc.) was not possible, DNA analysis was
applied. DNA was isolated from 20 skeletal remains (bone and tooth samples) and
six reference samples (blood from living relatives) and amplified using
PowerPlex(r) Fusion and PowerPlex(r) Y23 kits. DNA profiles were generated for
all reference samples and 17 skeletal remains. A statistical analysis
(calculation of paternity, maternity, and sibling indexes and matching
probabilities) resulted in 10 positive identifications. In this study, 5
individuals were identified based on one reference sample. This has once again
demonstrated the significance of DNA analysis in resolving the most complicated
cases, such as the identification of commingled human skeletal remains.
PMID- 28493428
TI - Optical, Thermal, and Mechanical Characterization of Ga2 Se3 -Added GLS Glass.
AB - Gallium lanthanum sulfide glass (GLS) has been widely studied in the last 40
years for middle-infrared applications. In this work, the results of the
substitution of selenium for sulphur in GLS glass are described. The samples are
prepared via melt-quench method in an argon-purged atmosphere. A wide range of
compositional substitutions are studied to define the glass-forming region of the
modified material. The complete substitution of Ga2 S3 by Ga2 Se3 is achieved by
involving new higher quenching rate techniques compared to those containing only
sulfides. The samples exhibiting glassy characteristics are further
characterized. In particular, the optical and thermal properties of the sample
are investigated in order to understand the role of selenium in the formation of
the glass. The addition of selenium to GLS glass generally results in a lower
glass transition temperature and an extended transmission window. Particularly,
the IR edge is found to be extended from about 9 um for GLS glass to about 15 um
for Se-added GLS glass defined by the 50% transmission point. Furthermore, the
addition of selenium does not affect the UV edge dramatically. The role of
selenium is hypothesized in the glass formation to explain these changes.
PMID- 28493429
TI - Trust and risk: a model for medical education.
AB - CONTEXT: Health care delivery, and therefore medical education, is an inherently
risky business. Although control mechanisms, such as external audit and
accreditation, are designed to manage risk in clinical settings, another approach
is 'trust'. The use of entrustable professional activities (EPAs) represents a
deliberate way in which this is operationalised as a workplace-based assessment.
Once engaged with the concept, clinical teachers and medical educators may have
further questions about trust. OBJECTIVES: This narrative overview of the trust
literature explores how risk, trust and control intersect with current thinking
in medical education, and makes suggestions for potential directions of enquiry.
METHODS: Beyond EPAs, the importance of trust in health care and medical
education is reviewed, followed by a brief history of trust research in the wider
literature. Interpersonal and organisational levels of trust and a model of trust
from the management literature are used to provide the framework with which to
decipher trust decisions in health care and medical education, in which risk and
vulnerability are inherent. CONCLUSIONS: In workplace learning and assessment,
the language of 'trust' may offer a more authentic and practical vocabulary than
that of 'competency' because clinical and professional risks are explicitly
considered. There are many other trust relationships in health care and medical
education. At the most basic level, it is helpful to clearly delineate who is the
trustor, the trustee, and for what task. Each relationship has interpersonal and
organisational elements. Understanding and considered utilisation of trust and
control mechanisms in health care and medical education may lead to systems that
maturely manage risk while actively encouraging trust and empowerment.
PMID- 28493431
TI - Breaking the real language barrier in care for older people.
PMID- 28493430
TI - First case of bacteremia caused by Janibacter hoylei.
AB - Janibacter hoylei has previously been isolated only from an air sample in the
upper atmosphere and clinical significance of J. hoylei was not yet established.
Herein, we report a case of bacteremia caused by J. hoylei. An 8-week-old
previously healthy male infant presented to the emergency room with fever. Blood
culture yielded growth of Gram-positive bacilli and this microorganism could not
be identified with conventional phenotypic methods. The isolate was identified by
16S rRNA gene sequencing, and the patient was successfully treated with
vancomycin. To our knowledge, this is the first report of the recovery of J.
hoylei in humans. This case shows that J. hoylei can be a potential pathogen in
young children.
PMID- 28493432
TI - Phenol metabolism and preservation of fresh in-hull walnut stored in modified
atmosphere packaging.
AB - BACKGROUND: The effects of modified atmosphere packaging (MAP) on phenol
metabolism and preservation of fresh in-hull walnuts have been investigated.
Fruit was packaged under MAP1 (film thickness, 30 MUm), MAP2 (45 MUm) and MAP3
(50 MUm) and stored at -0.5 to 1.0 degrees C for up to 60 days. RESULTS:
Firmness, soluble solid concentration, total phenols, total flavonoids and total
antioxidant activity of the green hull were maintained at higher levels under the
MAP conditions, whereas decay incidence was lower compared to the control during
storage. Green hull of fruit under MAP conditions contained lower polyphenol
oxidase activity than the control and the peroxidase activity was at a similar
level to the control after 18 days. Phenylalanine ammonialyase activity was
enhanced by MAP conditions, with two peaks on days 18 and 36. Until day 60, the
peroxide value and acid value of kernel oils under MAP conditions were lower than
that of the control. CONCLUSION: The MAP3 treatment was most effective for
maintaining kernel quality. The protective role of MAP conditions on phenolic
contents in green hull may contribute to the mitigation of decay and the
maintenance of kernel quality. (c) 2017 Society of Chemical Industry.
PMID- 28493433
TI - Highly Active and Iso-Selective Catalysts for the Ring-Opening Polymerization of
Cyclic Esters using Group 2 Metal Initiators.
AB - A series of alkali and alkaline earth (Ae) metal complexes bearing 1,2
phenylene(bis-diphenylphosphinothioic/selenoic amine) [{Ph2 P(E)NH}2 C6 H4 ] (E=S
(1-H2); Se (2-H2) ligands are reported. Alkali metal complexes [{Ph2 P(S)N}2 C6
H4 ]Na(THF)4 (3 a) [{Ph2 P(Se)N}2 C6 H4 ]Na(THF)4 (3 b), and [{Ph2 P(Se)N}2 C6 H4
]K(THF)5 (4 b) were obtained in good yield by treating protic ligands 1-H2 or 2
H2 with metal hexamethyldisilazides [MN(SiMe3 )2 ] (M=Na or K) at ambient
temperature. The Ae metal complexes formulated as [{Ph2 P(E)N}2 C6 H4 ]M(THF)3
[E=S, M=Ca (5 a), Sr (6 a), Ba (7 a); E=Se, M=Ca (5 b), Sr (6 b), Ba (7 b)] can
be synthesized by using two routes. The molecular structures of the free ligand 1
H2 and metal complexes 5 a,b-7 a,b in their solid states were established.
Complexes 3 a and 3 b are isostructural; however, in complex 4 b, an attachment
different from ligand 2 was observed. The complexes 5 a,b-7 a,b are isostructural
and each metal ion exhibits a distorted pentagonal bipyramidal geometry around
it. All Ae metal complexes 5 a,b-7 a,b were tested for the ring-opening
polymerization (ROP) of racemic lactide (rac-LA) and epsilon-caprolactone
(epsilon-CL) at room temperature. Calcium complexes 5 a and 5 b show excellent
iso-selectivity, with Pi values of 0.78-0.87 at 298 K and with a high degree of
polymerization control, whereas the corresponding strontium complexes 6 a and 6 b
exhibit moderate iso-selectivity, and barium complexes 7 a and 7 b yield only
atactic polylactides (PLAs). In all cases, the catalyst initiates the ROP
catalytic cycle in the absence of any external initiator. Kinetic studies of the
polymerization reactions indicate the relative order of polymerization rate
increases with increase in the size of the metal ion: Ba>Sr>Ca.
PMID- 28493434
TI - Carbon Thin Film Wrapped around a Three-Dimensional Nitrogen-Doped Carbon
Scaffold for Superior-Performance Supercapacitors.
AB - A carbon thin film/carbon foam core/sheath structure was synthesized by chemical
vapor deposition (CVD) on carbonized melamine foam. It has a specific capacitance
of 310 F g-1 at a current density of 1 A g-1 and shows outstanding
electrochemical performance in both aqueous and water-in-salt electrolytes.
Electrochemical analysis by cyclic voltammetry and galvanostatic charge/discharge
testing revealed a large capacitive contribution up to more than 90 % of its
total capacitance. The core/sheath structure has advantages in ion transport and
a high degree of utilization of the electrode surface, and the synthetic process
provides a way to coat carbon thin film on any substrate by nickel-catalyzed CVD.
PMID- 28493435
TI - A Fast Peak-Searching Algorithm for Ultrasonic Elastography.
AB - Tissue axial strain estimation with ultrasound elastography has become a hot
field in recent years. However, for keypoints tracking-based elastography
algorithms, locating extrema in multimodal ultrasonic radiofrequency signals is
still a challenging problem. In this paper, a new method is proposed to locate
the local maxima and minima of the RF signals directly without derivation
operation. This algorithm can accurately locate extrema even if disturbed peaks
resulting from different noise exist. Furthermore, the new algorithm can speed up
approximately 79% of the implementation process as compared with the standard
cross-correlation method on the same computing platform. In addition, the
elastographic signal-to-noise ratio and the contrast-to-noise ratio are also
significantly improved with this new method.
PMID- 28493436
TI - Enantioselective analysis of bambuterol in human plasma using microwave-assisted
chiral derivatization coupled with ultra high performance liquid chromatography
and tandem mass spectrometry.
AB - In this study, an enantioselective analytical method based on microwave-assisted
chiral derivatization coupled with ultra high performance liquid chromatography
and tandem mass spectrometry was developed for the determination of bambuterol
enantiomers in human plasma. The chiral derivatization reaction was greatly
accelerated by microwave irradiation. Under the optimized conditions, both the
derivatization time and separation time on column was only 3 min, and the lower
limit of quantification was 2.5 pg/mL. The recoveries were in the range of 90.1
93.0% without significant matrix effect. Compared with the conventional heating
chiral derivatization, microwave-assisted chiral derivatization obtained higher
chiral derivatization yields with much shorter time due to the effect of
microwave irradiation. Furthermore, the racemization during the derivatization
reaction was systematically investigated. The results showed the concentration of
acetic acid and the reaction time had significant effects on the racemization,
which could be well controlled during microwave-assisted chiral derivatization
for the short reaction time. Finally, this novel approach was demonstrated by
determining bambuterol in human plasma of a clinical pharmacokinetic study in
eight healthy volunteers. On the basis of the results, microwave-assisted chiral
derivatization coupled with ultra high performance liquid chromatography and
tandem mass spectrometry as a simple and effective enantioselective analysis
technique for the determination of chiral drugs in complex biological samples
showed great promise.
PMID- 28493437
TI - Extended axial imaging range, widefield swept source optical coherence tomography
angiography.
AB - We developed a high-speed, swept source OCT system for widefield OCT angiography
(OCTA) imaging. The system has an extended axial imaging range of 6.6 mm. An
electrical lens is used for fast, automatic focusing. The recently developed
split-spectrum amplitude and phase-gradient angiography allow high-resolution
OCTA imaging with only two B-scan repetitions. An improved post-processing
algorithm effectively removed trigger jitter artifacts and reduced noise in the
flow signal. We demonstrated high contrast 3 mm*3 mm OCTA image with 400*400
pixels acquired in 3 seconds and high-definition 8 mm*6 mm and 12 mm*6 mm OCTA
images with 850*400 pixels obtained in 4 seconds. A widefield 8 mm*11 mm OCTA
image is produced by montaging two 8 mm*6 mm scans. An ultra-widefield (with a
maximum of 22 mm along both vertical and horizontal directions) capillary
resolution OCTA image is obtained by montaging six 12 mm*6 mm scans.
PMID- 28493439
TI - Very late presentation of a disorder of sex development.
AB - Disorders of sex development generally present in the neonatal period with
ambiguity of external genitalia. We report a very old male patient presenting at
75 years because of panhypopituitarism and a large nonsecreting pituitary
macroadenoma secondary to long-standing primary hypogonadism due to 46,XX sex
reversal disorder now first diagnosed. Sex development disorders may go
unrecognised for the entire life span, despite infertility and long-standing
primary gonadic failure may lead to uncommon complications.
PMID- 28493438
TI - Deficient activity of alanyl-tRNA synthetase underlies an autosomal recessive
syndrome of progressive microcephaly, hypomyelination, and epileptic
encephalopathy.
AB - Aminoacyl-transfer RNA (tRNA) synthetases ligate amino acids to specific tRNAs
and are essential for protein synthesis. Although alanyl-tRNA synthetase (AARS)
is a synthetase implicated in a wide range of neurological disorders from Charcot
Marie-Tooth disease to infantile epileptic encephalopathy, there have been
limited data on their pathogenesis. Here, we report loss-of-function mutations in
AARS in two siblings with progressive microcephaly with hypomyelination,
intractable epilepsy, and spasticity. Whole-exome sequencing identified that the
affected individuals were compound heterozygous for mutations in AARS gene,
c.2067dupC (p.Tyr690Leufs*3) and c.2738G>A (p.Gly913Asp). A lymphoblastoid cell
line developed from one of the affected individuals showed a strong reduction in
AARS abundance. The mutations decrease aminoacylation efficiency by 70%-90%. The
p.Tyr690Leufs*3 mutation also abolished editing activity required for hydrolyzing
misacylated tRNAs, thereby increasing errors during aminoacylation. Our study has
extended potential mechanisms underlying AARS-related disorders to include
destabilization of the protein, aminoacylation dysfunction, and defective editing
activity.
PMID- 28493440
TI - Tear production, intraocular pressure and conjunctival bacterial flora in
selected captive wild ruminants.
AB - OBJECTIVE: Evaluation of tear production (Schirmer's tear test, STT) and
measurement of intraocular pressure (IOP) were performed in a population of
captive wild ungulates in a Slovenian ZOO during routine annual health check.
ANIMALS STUDIED: In total, 10 fallow deer (Dama dama), 25 mouflons (Ovis aries
musimon), 20 alpine ibexes (Capra ibex), and three alpine chamois (Rupicapra
rupicapra) were included in the study. METHODS: Tear production was performed by
Schirmer's tear test, IOP was measured with an applanation tonometer, and
ophthalmological examination was conducted with slit-lamp biomicroscopy and
indirect ophthalmoscopy. Conjunctival swabs were taken and submitted for aerobic
bacteriology and for detection of Chlamydia spp. and Mycoplasma spp. tested by
PCR. RESULTS: Average tear production (in mm/min) was 17.8 +/- 3.16 for fallow
deer, 17.9 +/- 3.87 for mouflons, and 11.7 +/- 3.87 for ibexes. Mean intraocular
pressure (IOP, in mm Hg) was 14.1 +/- 2.48 for fallow deer, 14.9 +/- 2.20 for
mouflons, and 13.1 +/- 2.43 for ibexes. For chamois, average tear production and
IOP were 14.5 +/- 3.0 and 10.2 +/- 2.5, respectively; this is the first record of
STT I and IOP in chamois. Bacteriological swabs were positive for bacteria in
100% of the fallow deer, 56% of mouflons, 35% of ibexes, and 100% of chamois.
Gram-positive bacteria were predominant. Moraxella spp., Chlamydia spp., and
Mycoplasma spp. were not detected. CONCLUSION: The reported values were obtained
in animals under manual restraint only to be applicative in similar conditions.
PMID- 28493441
TI - UHPLC-ESI-MS/MS determination and pharmacokinetics of pinoresinol glucoside and
chlorogenic acid in rat plasma after oral administration of Eucommia ulmoides
Oliv extract.
AB - This study aimed to develop a specific UHPLC-ESI-MS/MS method for simultaneous
determination and pharmacokinetics of pinoresinol glucoside and chlorogenic acid
in rat plasma after oral administration of Eucommia ulmoides. The chromatographic
separation was achieved on a Hypersil GOLD column with gradient elution by using
a mixture of 0.1% formic acid aqueous solution and acetonitrile as the mobile
phase at a flow rate of 200 MUL/min. A tandem mass spectrometric detection was
conducted using multiple-reaction monitoring via an electrospray ionization
source in negative ionization mode. Samples were pre-treated by a single-step
protein precipitation with acetonitrile, and bergenin was used as internal
standard. After oral administration of 3 mL/kg E. ulmoides extract in rats, the
maximum plasma concentrations of pinoresinol glucoside and chlorogenic acid were
57.44 and 61.04 ng/mL, respectively. The times to reach the maximum plasma
concentration were 40.00 and 23.33 min for pinoresinol glucoside and chlorogenic
acid, respectively. The intra- and inter-day precision (RSD) values for the two
analytes were <2.46 and 5.15%, respectively, and the accuracy (RE) values ranged
from -12.76 to 0.00. This is the first study on pharmacokinetics of bioactive
compounds in rat plasma after oral administration of E. ulmoides extract.
PMID- 28493442
TI - uPA-derived peptide, A6 is involved in the suppression of lipopolysaccaride
promoted inflammatory osteoclastogenesis and the resultant bone loss.
AB - INTRODUCTION: Chronic inflammatory diseases such as rheumatoid arthritis and
periodontitis frequently cause bone destruction. Inflammation-induced bone loss
results from the increase of bone-resorbing osteoclasts. Recently, we
demonstrated that urokinase type plasminogen activator (uPA) suppressed
lipopolysaccaride (LPS)-inflammatory osteoclastogenesis through the adenosine
monophosphate-activated protein kinase (AMPK) pathway, whereas its receptor
(uPAR) promoted that through the Akt pathway. METHODS: We investigated the
effects of uPA-derived peptide (A6) in the LPS-induced inflammatory
osteoclastogenesis and bone destruction. RESULTS: We found that A6 attenuated
inflammatory osteoclastogenesis and bone loss induced by LPS in mice. We also
showed that A6 attenuated the LPS-promoted inflammatory osteoclastogenesis by
inactivation of NF-kappaB in RAW264.7 mouse monocyte/macrophage lineage cells.
Furthermore, we showed that A6 attenuated the Akt phosphorylation, and promoted
the AMPK phosphorylation. CONCLUSION: A6 is involved in the suppression of LPS
promoted inflammatory osteoclastgensis and bone destruction by regulating the
AMPK and Akt pathways. These findings provide a basis for clinical strategies to
improve the bone loss caused by inflammatory diseases.
PMID- 28493444
TI - Impact of hyperlipidaemia on intermediary metabolism, faecal microbial
metabolites and urinary characteristics of lipoprotein lipase deficient vs.
normal cats.
AB - Findings in humans and rats indicate that hyperlipidaemia may be associated with
enhanced endogenous oxalate (Ox) synthesis, which may be relevant for calcium
oxalate (CaOx) urolith formation. Moreover, changes in lipid metabolism are
proposed to negatively affect gut microbiota. This study aimed to investigate
those potential interactions in hyperlipidaemic cats. Therefore, 10 normal
control cats and seven lipoprotein lipase (LPL)-deficient cats were fed a low-fat
diet for seven weeks. During the last week of the study, cats were housed in
metabolic cages to collect urine and faeces. Blood was taken on the last day of
the study. The LPL-deficient cats had significantly higher serum triglyceride
concentrations than normal cats, while lactate dehydrogenase (LDH) activity was
not different. Urinary relative supersaturation with CaOx, urinary Ox, calcium,
and citrate excretions, and urine pH did not differ between groups. Lower faecal
acetic, propionic and total short-chain fatty acid concentrations were observed
in the LPL-deficient cats. In conclusion, hyperlipidaemia does not appear to be a
specific risk factor for CaOx urolith formation in cats. In contrast to results
in rats, hyperlipidaemia was not accompanied by elevated serum LDH activity. As
LDH can synthesise Ox from glycolate or other precursors, this might be one
possible explanation for the similar urinary parameters in the LPL-deficient and
normal cats. Non-diet-induced hyperlipidaemia was not associated with marked
changes in faecal microbial metabolites, suggesting no differences in the
composition of the intestinal microbiota.
PMID- 28493443
TI - Natural alkaloid bouchardatine ameliorates metabolic disorders in high-fat diet
fed mice by stimulating the sirtuin 1/liver kinase B-1/AMPK axis.
AB - BACKGROUND AND PURPOSE: Promoting energy metabolism is known to provide
therapeutic effects for obesity and associated metabolic disorders. The present
study evaluated the therapeutic effects of the newly identified bouchardatine
(Bou) on obesity-associated metabolic disorders and the molecular mechanisms of
these effects. EXPERIMENTAL APPROACH: The molecular mode of action of Bou for its
effects on lipid metabolism was first examined in 3T3-L1 adipocytes and HepG2
cells. This was followed by an evaluation of its metabolic effects in mice fed a
high-fat diet for 16 weeks with Bou being administered in the last 5 weeks.
Further mechanistic investigations were conducted in pertinent organs of the mice
and relevant cell models. KEY RESULTS: In 3T3-L1 adipocytes, Bou reduced lipid
content and increased sirtuin 1 (SIRT1) activity to facilitate liver kinase B1
(LKB1) activation of AMPK. Chronic administration of Bou (50 mg?kg-1 every other
day) in mice significantly attenuated high-fat diet-induced increases in body
weight gain, dyslipidaemia and fatty liver without affecting food intake and no
adverse effects were detected. These metabolic effects were associated with
activation of the SIRT1-LKB1-AMPK signalling pathway in adipose tissue and liver.
Of particular note, UCP1 expression and mitochondrial biogenesis were increased
in both white and brown adipose tissues of Bou-treated mice. Incubation with Bou
induced similar changes in primary brown adipocytes isolated from mice.
CONCLUSIONS AND IMPLICATIONS: Bou may have therapeutic potential for obesity
related metabolic diseases by increasing the capacity of energy expenditure in
adipose tissues and liver through a mechanism involving the SIRT1-LKB1-AMPK axis.
PMID- 28493445
TI - Informed consent, community engagement, and study participation at a research
site in Kigali, Rwanda.
AB - People enroll in medical research for many reasons ranging from decisions
regarding their own or family members' health situation to broader considerations
including access to health and financial resources. In socially vulnerable
communities the choice to participate is often based on a risk-benefit assessment
that goes beyond the medical aspects of the research, and considers the benefits
received. In this qualitative study, we examined the motivations of Rwandan women
to participate in a non-commercial collaborative research study examining the
safety, acceptability, and adherence of a contraceptive vaginal ring in Rwanda
juxtaposed with the perceptions of the research within the community. 351 women
attended the screening visit, four were excluded because they were not able to
complete the assessment of understanding. The remaining participants' ages ranged
from 17 to 38 and 80% had primary level of education or below. 120 were enrolled.
Findings highlighted motivations for joining the study that were relayed both
formally by the clinic (e.g. testing and treatment) and informally by the
community including the positive aspects of the ring. There were also some
negative rumors circulating regarding the research site, likely from excluded
participants who faced potential stigma based on that exclusion. It was
understood by most participants that they were enrolled in a research study and
participants actively sought out enrollment in the research for a variety of
reasons. The experiences demonstrate that although inequalities in access to
health care may create conflicting situations around the study, it is possible to
form partnerships between a research center and participants/their partners, for
research about reproductive health.
PMID- 28493446
TI - Family perception of unmet support needs following a diagnosis of congenital
coronary anomaly in children: Results of a survey.
AB - BACKGROUND: Long-term outcome data on patients with anomalous aortic origin of
coronary arteries (AAOCA) is sparse and they are often managed in a nonuniform
manner. There is subjective perception of anxiety and unmet needs in these
patients and families. METHODS: An online survey of 13 questions was sent to 74
families of patients with AAOCA between May and October 2015. Descriptive
statistics were performed. RESULTS: A total of 31 (47%) families responded. Of
these, 27 expressed the need to interact with other patients/families with AAOCA.
The majority were interested in either face-to-face meetings (77%) or online
support groups (71%). Regarding content of the meeting, 74% were interested in
brief talks by medical personnel/families, 58% suggested informal interactions
with families, 55% proposed a structured discussion with a moderator and 39%
mentioned fun activities/games. Regarding participants in these meetings, 90%
would like to include healthcare providers, 61% suggested including family
friends, 58% wished to include psychologists and 16% mentioned including social
workers. The families currently use various social media including Facebook
(87%), YouTube (39%), Google+ (36%), and LinkedIn (32%). For future online
resources, 77% of families would like a Facebook site, an informative website
(58%), a blog (52%), or an open forum (29%). The majority of the families (77%)
were interested in attending a dedicated AAOCA meeting. CONCLUSION: There appears
to be an unmet need for family support in those affected by AAOCA, a substantial
life changing diagnosis for patients and families. Further research is needed to
assess quality of life in this population.
PMID- 28493448
TI - Utility of an immunocytochemical assay using aqueous humor in the diagnosis of
feline infectious peritonitis.
AB - OBJECTIVE: In cats suffering from feline infectious peritonitis (FIP) without
effusion, antemortem diagnosis is challenging. Uveitis is common in these cats.
It was the aim of this study to evaluate sensitivity and specificity of an
immunocytochemical assay (ICC) in aqueous humor of cats suspected of having FIP.
ANIMALS STUDIED: The study included 26 cats with immunohistochemically confirmed
FIP and 12 control cats for which FIP was suspected due to similar clinical or
laboratory changes, but which suffered from other diseases confirmed via
histopathology. PROCEDURES: All aqueous humor samples were collected postmortem
by paracentesis. ICC was carried out as avidin-biotin complex method.
Sensitivity, specificity, and the overall accuracy including 95% confidence
intervals (95% CI) were calculated. RESULTS: Immunocytochemistry was positive in
16 of 25 cats with FIP and 2 of 11 control cats (one cat with lymphoma, one with
pulmonary adenocarcinoma). Aqueous humor samples of one cat with FIP and of one
control cat were excluded from statistical analysis. Sensitivity was 64.0% (95%
CI: 42.5-82.0); specificity 81.8% (95% CI: 48.2-97.7); and overall accuracy 69.4%
(95% CI: 51.9-83.7). CONCLUSIONS: As false-positive results occurred and
specificity is most important in the diagnosis of FIP, the diagnostic utility of
ICC in aqueous humor is limited. Further studies are required to clarify the
origin of false-positive ICC results.
PMID- 28493447
TI - The outcomes and prognostic factors of fetal hydrothorax associated with trisomy
21.
AB - OBJECTIVES: To determine the characteristics, outcomes, and prognostic factors of
fetal hydrothorax (FHT) with trisomy 21. METHODS: A nationwide survey was
conducted on FHT fetuses with trisomy 21 delivered after 22 weeks' gestation
between January 2007 and December 2011 at perinatal centers. RESULTS: The 91
cases of FHT with trisomy 21 included 28 (30.8%) diagnosed in utero and 63
(69.2%) diagnosed after birth. The natural remission rate was 6.6% (6/91).
Thoracoamniotic shunting was performed in 14.3% (13/91) of cases. The survival
rates of the hydropic, nonhydropic, and total cases were 47.0% (31/66), 84.0%
(21/25), and 57.1% (52/91), respectively. The crude odds ratio for death was 8.2
(p = 0.003) for fetuses diagnosed at 26-30 weeks of gestational age (vs >=30
weeks), 5.9 (p = 0.003) for hydrops, 4.0 (p = 0.04) for bilateral pleural
effusion, 0.68 (p = 0.42) for associated cardiovascular anomalies, and 2.1 (p =
0.26) for thoracoamniotic shunting (vs no fetal therapy). CONCLUSIONS: The
prognosis of FHT with trisomy 21 was not very poor, but it was still worse than
that of primary FHT. Hydrops, an early gestational age at the diagnosis and
bilateral effusion, but not associated anomalies, were risk factors for death.
Fetal therapy showed no survival benefit for FHT with trisomy 21. (c) 2017 John
Wiley & Sons, Ltd.
PMID- 28493449
TI - Formation of Tough Films by Evaporation of Water from Dispersions of Elastomer
Microspheres Crosslinked with Rotaxane Supramolecules.
AB - Compared to rigid microspheres that consist, for example, of polystyrene or
silica, soft and deformable elastomer microspheres can be used to generate
colorless transparent films upon evaporating the solvent from microsphere
containing dispersions. To obtain tough films, a post-polymerization reaction to
crosslink the microspheres is usually necessary, which requires extra additives
during the drying process. This restriction renders this film-formation
technology complex and rather unsuitable for applications in which impurities are
undesirable. In the present study, it is demonstrated that tough elastomer
microspheres that are crosslinked with rotaxanes can form tough bulk films upon
evaporation of water from microsphere dispersions, so that post-polymerization
reactions are not required. The results of this study should thus lead to new
applications including coatings for biomaterials that need complete removal of
all impurities from the materials prior to use.
PMID- 28493450
TI - Functionally specialised birds respond flexibly to seasonal changes in fruit
availability.
AB - Interactions between resource and consumer species result in complex ecological
networks. The overall structure of these networks is often stable in space and
time, but little is known about the temporal stability of the functional roles of
consumer species in these networks. We used a trait-based approach to investigate
whether consumers (frugivorous birds) show similar degrees of functional
specialisation on resources (plants) in ecological networks across seasons. We
additionally tested whether closely related bird species have similar degrees of
functional specialisation and whether birds that are functionally specialised on
specific resource types within a season are flexible in switching to other
resource types in other seasons. We analysed four seasonal replicates of two
species-rich plant-frugivore networks from the tropical Andes. To quantify fruit
preferences of frugivorous birds, we projected their interactions with plants
into a multidimensional plant trait space. To measure functional specialisation
of birds, we calculated a species' functional niche breadth (the extent of
seasonal plant trait space utilised by a particular bird) and functional
originality (the extent to which a bird species' fruit preference functionally
differs from those of other species in a seasonal network). We additionally
calculated functional flexibility, i.e. the ability of bird species to change
their fruit preference across seasons in response to variation in plant
resources. Functional specialisation of bird species varied more among species
than across seasons, and phylogenetically similar bird species showed similar
degrees of functional niche breadth (phylogenetic signal lambda = 0.81) and
functional originality (lambda = 0.89). Additionally, we found that birds with
high functional flexibility across seasons had narrow functional niche breadth
and high functional originality per season, suggesting that birds that are
seasonally specialised on particular resources are most flexible in switching to
other fruit resources across seasons. The high flexibility of functionally
specialised bird species to switch seasonally to other resources challenges the
view that consumer species rely on functionally similar resources throughout the
year. This flexibility of consumer species may be an important, but widely
neglected mechanism that could potentially stabilise consumer-resource networks
in response to human disturbance and environmental change.
PMID- 28493451
TI - The effect of an electronic health record-based tool on abnormal pediatric blood
pressure recognition.
AB - BACKGROUND: Recognition of high blood pressure (BP) in children is poor, partly
due to the need to compute age-sex-height referenced percentiles. This study
examined the change in abnormal BP recognition before versus after the
introduction of an electronic health record (EHR) app designed to calculate BP
percentiles with a training lecture. METHODS AND RESULTS: Clinical data were
extracted on all ambulatory, non-urgent encounters for children 3-18 years old
seen in primary care, endocrinology, cardiology, or nephrology clinics at an
urban, academic hospital in the year before and the year after app introduction.
Outpatients with at least 1 BP above the age-gender-height referenced 90th
percentile were included. Abnormal BP recognition was defined as a BP related ICD
9 code, referral to nephrology or cardiology, an echocardiogram or renal
ultrasound to evaluate BP concern, or a follow-up primary care visit for BP
monitoring. Multivariable adjusted logistic regression compared odds of
recognition before and after app introduction. Of 78 768 clinical encounters,
3521 had abnormal BP in the pre- and 3358 in the post-app period. App use
occurred in 13% of elevated BP visits. Overall, abnormal BP was recognized in
4.9% pre-app period visits and 7.1% of visits post-app (P < .0001). Recognition
was significantly higher when the app was actually used (adjusted OR 3.17 95% CI
2.29-4.41, P < .001). Without app use recognition was not different. CONCLUSIONS:
BP app advent modestly increased abnormal BP recognition in the entire cohort,
but actual app use was associated with significantly higher recognition.
Predictors of abnormal BP recognition deserve further scrutiny.
PMID- 28493452
TI - Suitability of selected chromatographic columns for analysis of fatty acids in
dialyzed patients.
AB - Gas chromatography-mass spectrometry is a preferred method for fatty acid (FA)
analysis in biofluids from patients with metabolic diseases. Complex
characteristics of FAs make their analysis particularly challenging. Selection of
an appropriate chromatographic column is particularly important component of the
process as it provides optimal separation and detection of possibly all FAs
present in the sample. However, no accurate protocol for comparative evaluation
of capillary columns for the analysis of whole serum FA profile in patients with
chronic kidney disease (CKD) has been developed thus far. Therefore, in the
present study four columns were examined to select the one providing optimal
separation and determination of FA profiles in this group of patients. Moreover,
serum FA profiles obtained with the selected column in CKD patients subjected to
peritoneal dialysis and healthy controls were compared. Thirty-seven component
FAME Mix and sera from CKD patients were used to optimize chromatographic
conditions and to select the most appropriate column. The ZB-5 column turned out
to be the most appropriate for the analysis of whole FA profile in CKD patients'
sera. Then, this column was used to compare FA profiles in patients subjected to
peritoneal dialysis and in healthy controls. The analysis demonstrated many
abnormalities in the FA profile of CKD patients. Further studies involving larger
groups of patients presenting with other stages of CKD are required to explain
the impact of the disease progression on composition of serum FAs.
PMID- 28493453
TI - A survey to establish current practice in addressing work participation with
inflammatory arthritis in the Irish clinical setting.
PMID- 28493454
TI - Cryo scanning electron microscopy of Plasmodium falciparum-infected erythrocytes.
AB - Plasmodium falciparum invades erythrocytes as an essential part of their life
cycle. While living inside erythrocytes, the parasite remodels the cell's
intracellular organization as well as its outer surface. Late trophozoite-stage
parasites and schizonts introduce numerous small protrusions on the erythrocyte
surface, called knobs. Current methods for studying these knobs include atomic
force microscopy and electron microscopy. Standard electron microscopy methods
rely on chemical fixation and dehydration modifying cell size. Here, a novel
method is presented using rapid freezing and scanning electron microscopy under
cryogenic conditions allowing for high resolution and magnification of
erythrocytes. This novel technique can be used for precise estimates of knob
density and for studies on cytoadhesion.
PMID- 28493460
TI - Single-cell genomics reveals pyrrolysine-encoding potential in members of
uncultivated archaeal candidate division MSBL1.
AB - Pyrrolysine (Pyl), the 22nd canonical amino acid, is only decoded and synthesized
by a limited number of organisms in the domains Archaea and Bacteria. Pyl is
encoded by the amber codon UAG, typically a stop codon. To date, all known Pyl
decoding archaea are able to carry out methylotrophic methanogenesis. The
functionality of methylamine methyltransferases, an important component of
corrinoid-dependent methyltransfer reactions, depends on the presence of Pyl.
Here, we present a putative pyl gene cluster obtained from single-cell genomes of
the archaeal Mediterranean Sea Brine Lakes group 1 (MSBL1) from the Red Sea.
Functional annotation of the MSBL1 single cell amplified genomes (SAGs) also
revealed a complete corrinoid-dependent methyl-transfer pathway suggesting that
members of MSBL1 may possibly be capable of synthesizing Pyl and metabolizing
methylated amines.
PMID- 28493459
TI - Enhanced NOLC1 promotes cell senescence and represses hepatocellular carcinoma
cell proliferation by disturbing the organization of nucleolus.
AB - The nucleolus is a key organelle that is responsible for the synthesis of rRNA
and assembly of ribosomal subunits, which is also the center of metabolic control
because of the critical role of ribosomes in protein synthesis. Perturbations of
rRNA biogenesis are closely related to cell senescence and tumor progression;
however, the underlying molecular mechanisms are not well understood. Here, we
report that cellular senescence-inhibited gene (CSIG) knockdown up-regulated
NOLC1 by stabilizing the 5'UTR of NOLC1 mRNA, and elevated NOLC1 induced the
retention of NOG1 in the nucleolus, which is responsible for rRNA processing.
Besides, the expression of NOLC1 was negatively correlated with CSIG in the aged
mouse tissue and replicative senescent 2BS cells, and the down-regulation of
NOLC1 could rescue CSIG knockdown-induced 2BS senescence. Additionally, NOLC1
expression was decreased in human hepatocellular carcinoma (HCC) tissue, and the
ectopic expression of NOLC1 repressed the proliferation of HCC cells and tumor
growth in a HCC xenograft model.
PMID- 28493461
TI - Ophthalmic nepafenac use in the Netherlands and Denmark.
AB - PURPOSE: To describe nepafenac use in the Netherlands and Denmark with reference
to its approved indications. For context, we also describe the use of ketorolac
and diclofenac. METHODS: We identified users in the PHARMO Database Network (the
Netherlands, 2008-2013) and the Danish national health registers (Denmark, 1994
2014). We described prevalence of cataract surgery and duration of use in
patients with cataract surgery with and without diabetes. RESULTS: In the
Netherlands, 9530 nepafenac users (mean age, 71 years; 60% women) contributed 12
691 therapy episodes, of which 21% had a recently recorded cataract surgery. Of
2266 episodes in adult non-diabetic patients with cataract surgery, 60% had one
bottle dispensed (treatment duration <=21 days). Of 441 episodes in adult
diabetic patients with cataract surgery, 90% had up to two bottles dispensed
(<=60 days). Denmark had 60 403 nepafenac users (mean age, 72 years; 58% women)
and 73 648 episodes (41% had recorded cataract surgery). Of 26 649 nepafenac
episodes in adult non-diabetic patients with cataract surgery, 92% had one bottle
dispensed. Of 3801 episodes in adult diabetic patients with cataract surgery,
99.8% had up to two bottles dispensed. Use patterns of nepafenac, ketorolac and
diclofenac were roughly similar in the Netherlands, but not in Denmark.
CONCLUSION: Less than half of therapy episodes were related to cataract surgery;
around 90% of episodes with surgery were within the approved duration.
Underrecording of ophthalmic conditions and procedures was a challenge in this
study.
PMID- 28493462
TI - Strong Short-Range Cooperativity in Hydrogen-Bond Chains.
AB - Chains of hydrogen bonds such as those found in water and proteins are often
presumed to be more stable than the sum of the individual H bonds. However, the
energetics of cooperativity are complicated by solvent effects and the dynamics
of intermolecular interactions, meaning that information on cooperativity
typically is derived from theory or indirect structural data. Herein, we present
direct measurements of energetic cooperativity in an experimental system in which
the geometry and the number of H bonds in a chain were systematically controlled.
Strikingly, we found that adding a second H-bond donor to form a chain can almost
double the strength of the terminal H bond, while further extensions have little
effect. The experimental observations add weight to computations which have
suggested that strong, but short-range cooperative effects may occur in H-bond
chains.
PMID- 28493463
TI - Main predators of insect pests: screening and evaluation through comprehensive
indices.
AB - BACKGROUND: Predatory natural enemies play key functional roles in integrated
pest management. However, the screening and evaluation of the main predators of
insect pests has seldom been reported in the field. Here, we employed
comprehensive indices for evaluating the predation of a common pest (Ectropis
obliqua) by nine common spider species in Chinese tea plantations. RESULTS: We
established the relative dominance of the spider species and their phenological
overlap with the pest species, and analyzed DNA from the nine spider species
using targeted real-time quantitative polymerase chain reaction to identify the
residual DNA of E. obliqua. The predation rates and predation numbers per
predator were estimated by the positive rates of target fragments and the
residual minimum number of E. obliqua in predators' guts, respectively. The
results showed that only four spider species preyed on E. obliqua, and the order
of potential of the spiders to control E. obliqua from greatest to smallest was
Neoscona mellotteei, Xysticus ephippiatus, Evarcha albaria and Coleosoma
octomaculatum by the Z-score method. CONCLUSION: The orb-weaving spider N.
mellotteei has the maximum potential as a biological control agent of E. obliqua
in an integrated pest management strategy. An approach of screening and
evaluating main predators of insect pests through comprehensive indices was
preliminarily established. (c) 2017 Society of Chemical Industry.
PMID- 28493464
TI - First-trimester ultrasound screening for trisomy 21 based on maternal age, fetal
nuchal translucency, and different methods of ductus venosus assessment.
AB - OBJECTIVE: To examine whether combining the dichotomous assessment of the a-wave
and the ductus venosus (DV) pulsatility index for veins (PIV) measurement
improves first-trimester screening performance. METHODS: Retrospective study
performed at the University Hospital of Tuebingen based on singleton pregnancies
that underwent first-trimester screening including DV flow assessment. In each
case, the risk of trisomy 21 was calculated based on maternal age, fetal nuchal
translucency, and DV flow either as dichotomous classification of the a-wave, as
measurement of the DV PIV, or both. RESULTS: There were 5280 euploid fetuses and
127 fetuses with trisomy 21. The DV a-wave was reversed in 2.3% and 66.1% in the
euploid and trisomy 21 cases, respectively. The DV PIV measurements were above
the 95th percentile in 8.3% and 77.2% the euploid and trisomy 21 cases,
respectively. For a false positive rate of 3%, the detection rate for trisomy 21
based on maternal age, fetal NT, and DV flow is about 87% irrespective of whether
DV is examined as a continuous or dichotomous variable. The combination of both
resulted in a small decrease at 3% false positive rate. CONCLUSION: Assessment of
the DV a-wave and the DV PIV result in similar DRs. Combining these two
approaches does not appear to improve their individual screening performance. (c)
2017 John Wiley & Sons, Ltd.
PMID- 28493465
TI - Changes in right ventricular function assessed by echocardiography in dog models
of mild RV pressure overload.
AB - BACKGROUND: The assessment of hemodynamic change by echocardiography is
clinically useful in patients with pulmonary hypertension. Recently, mild
elevation of the mean pulmonary arterial pressure (PAP) has been shown to be
associated with increased mortality. However, changes in the echocardiographic
indices of right ventricular (RV) function are still unknown. The objective of
this study was to validate the relationship between echocardiographic indices of
RV function and right heart catheterization variables under a mild RV pressure
overload condition. METHODS AND RESULTS: Echocardiography and right heart
catheterization were performed in dog models of mild RV pressure overload induced
by thromboxane A2 analog (U46619) (n=7). The mean PAP was mildly increased
(19.3+/-1.1 mm Hg), and the cardiac index was decreased. Most echocardiographic
indices of RV function were significantly impaired even under a mild RV pressure
overload condition. Multivariate analysis revealed that the RV free wall
longitudinal strain (RVLS), standard deviation of the time-to-peak longitudinal
strain of RV six segments (RV-SD) by speckle-tracking echocardiography, and Tei
index were independent echocardiographic predictors of the mean PAP (free wall
RVLS, beta=-0.60, P<.001; RV-SD, beta=0.40, P=.011), pulmonary vascular
resistance (free wall RVLS, beta=-0.39, P=.020; RV-SD, beta=0.47, P=.0086; Tei
index, beta=0.34, P=.047), and cardiac index (Tei index, beta=-0.65, P<.001).
CONCLUSIONS: Free wall RVLS, RV-SD, and Tei index are useful for assessing the
hemodynamic change under a mild RV pressure overload condition.
PMID- 28493466
TI - 'It's Fast, It's Quick, It Stops Me Being Sick': How to influence preparation of
opioid tablets for injection.
AB - INTRODUCTION AND AIMS: Injection of pharmaceutical opioids (PO) among people who
inject drugs has increased in many countries. The common method for preparing PO
tablets for injection uses heat, resulting in greater particulate matter and
therefore increased risk of local infection risk and damage to veins and organs.
A cold preparation process has fewer risks, but this preparation method is not
commonly used. This study seeks to explore how people who inject PO learn to
prepare injections and how health promotion efforts could influence practice.
DESIGN AND METHODS: Between March and December 2013, qualitative interviews were
undertaken with 33 clients of Sydney's Medically Supervised Injecting Centre who
inject PO tablets regarding sources of knowledge and current preparation methods
for injection of POs. RESULTS: Overwhelmingly, the most commonly reported source
of knowledge around injection of tablets was others who inject. Most participants
reported heating the solution as the quickest way to administer the drug.
Attitudes to the use of wheel filters varied, with some participants reporting
that they would use the filters if they were shown how, while others reported a
number of barriers to using filters, including complexity of use. DISCUSSION AND
CONCLUSIONS: Harnessing the power of social connections may provide avenues for
education about safer injecting of tablets, including the use of wheel filters.
Further work is required to debunk myths about the relative potencies of cold
versus hot drug solution. Collaborations between harm reduction workers and peer
workers would assist in knowledge dissemination regarding safer injecting
practices.
PMID- 28493467
TI - Discovery of EGF Receptor Inhibitors That Are Selective for the d746
750/T790M/C797S Mutant through Structure-Based de Novo Design.
AB - Next-generation epidermal growth factor receptor (EGFR) inhibitors against the
d746-750/T790M/C797S mutation were discovered through two-track virtual screening
and de novo design. A number of nanomolar inhibitors were identified using 2-aryl
4-aminoquinazoline as the molecular core and the modified binding energy function
involving a proper dehydration term, which provides important structural insight
into the key principles for high inhibitory activities against the d746
750/T790M/C797S mutant. Furthermore, some of these EGFR inhibitors showed a
greater than 1000-fold selectivity for the d746-750/T790M/C797S mutant over the
wild type, as well as nanomolar activity against the mutant.
PMID- 28493468
TI - Insight into the success of whitefly biological control using parasitoids:
evidence from the Eretmocerus warrae-Trialeurodes vaporariorum system.
AB - BACKGROUND: Mechanisms behind the success and failure of whitefly biological
control using parasitoids are largely unknown. Here we use the Eretmocerus warrae
greenhouse whitefly system to investigate how the fluctuating density of the
parasitoid and its host affects three key parasitoid fitness parameters, host
searching, host feeding and parasitization, providing critical knowledge for
evaluation and development of whitefly biological control programmes. This is the
first such study in a parasitoid-whitefly system. RESULTS: Models used and
developed here show that (1) both host feeding and parasitism fit a type II
functional response; (2) overall parasitoid-caused whitefly mortality
significantly increases with growing density of both organisms and the parasitoid
density has a significantly more positive effect; (3) with a pro-synovigenic
nature, E. warrae allocate significantly more resources to parasitization than to
host feeding activity in low whitefly density and high parasitoid density; and
(4) low mutual interference among searching parasitoids encourages parasitoid
aggregation on host patches of high density. CONCLUSION: Regardless of greenhouse
whitefly density, the pest can be effectively controlled by release of E. warrae.
Our study provides insight into the success of whitefly biological control
programmes using the parasitoid augmentation approach. Models used and developed
here can also be employed to evaluate biological control programmes for other
parasitoid-whitefly systems. (c) 2017 Society of Chemical Industry.
PMID- 28493469
TI - Nature-Inspired Synthesis of Nanostructured Electrocatalysts through
Mineralization of Calcium Carbonate.
AB - Biomineralization is a biogenic process that produces elaborate inorganic and
organic hybrid materials in nature. Inspired by the natural process, this study
explored a new mineralization approach to create nanostructured CaCO3 films
composed of amorphous CaCO3 hemispheres by using catechol-rich polydopamine (PDA)
as a biomimetic mediator. The thus synthesized biomimetic CaCO3 was successfully
transformed to nanostructured films of metal-oxide minerals, such as FeOOH, CoCO3
, NiCO3 , and MnOOH, through a simple procedure. The CaCO3 -templated metal-oxide
minerals functioned as efficient electrocatalysts; a CaCO3 -templated cobalt
phosphate (nanoCoPi) film exhibited high stability as a water-oxidation
electrocatalyst with a current density of 1.5 mA cm-2 . The nanostructure of
nanoCoPi, consisting of individual nanoparticles (~70 nm) and numerous internal
pores (BET surface area: 3.17 m2 g-1 ), facilitated an additional charge
transfer pathway from the electrode to individual active sites of the catalyst.
This work demonstrates a plausible strategy for facile and green synthesis of
nanostructured electrocatalysts through biomimetic CaCO3 mineralization.
PMID- 28493470
TI - Prognostic significance of serum immunoglobulin paraprotein in patients with
diffuse large B cell lymphoma.
PMID- 28493471
TI - What role does the stress response have in congestive heart failure?
AB - This review is concerned with cardiac malfunction as a result of an imbalance in
protein proteostasis, the homeostatic balance between protein removal and
regeneration in a long remodeling process involving the endoplasmic reticulum
(ER) and the unfolded protein response (UPR). The importance of this is of
special significance with regard to cardiac function as a high energy requiring
muscular organ that has a high oxygen requirement and is highly dependent on
mitochondria. The importance of mitochondria is not only concerned with high
energy dependence on mitochondrial electron transport, but it also has a role in
the signaling between the mitochondria and the ER under stress. Proteins made in
the ER are folded as a result of sulfhydryl groups (-SH) and attractive and
repulsive reactions in the tertiary structure. We discuss how this matters with
respect to an imbalance between muscle breakdown and repair in a stressful
environment, especially as a result of oxidative and nitrosative byproducts of
mitochondrial activity. The normal repair is a remodeling, but under this
circumstance, the cell undergoes or even lysosomal "self eating" autophagy, or
even necrosis instead of apoptosis. We shall discuss the relationship of the UPR
pathway to chronic congestive heart failure (CHF).
PMID- 28493472
TI - Turf wars: exploring splenomegaly in sickle cell disease in malaria-endemic
regions.
AB - Sickle cell disease (SCD) is a group of recessively inherited disorders of
erythrocyte function that presents an ongoing threat to reducing childhood and
adult morbidity and mortality around the world. While decades of research have
led to improved survival for SCD patients in wealthy countries, survival remains
dismal in low- and middle-income countries. Much of the early mortality
associated with SCD is attributed to increased risk of infections due to early
loss of splenic function. In the West, bacterial infections with encapsulated
organisms are a primary concern. In sub-Saharan Africa, where the majority of
infants with SCD are born, the same is true. However malaria presents an
additional threat to survival. The search for factors that define variability in
sickle cell phenotypes should include environmental modifiers, such as malaria.
Further exploration of this relationship could lead to novel strategies to reduce
morbidity and mortality attributable to infections. In this review, we explore
the interactions between SCD, malaria and the spleen to better understand how
splenomegaly and splenic (dys)function may co-exist in patients with SCD living
in malaria-endemic areas.
PMID- 28493474
TI - Effects of heat stress and probiotic supplementation on protein functionality and
oxidative stability of ground chicken leg meat during display storage.
AB - BACKGROUND: The present study aimed to evaluate the effects of heat stress and
probiotic supplementation on protein functionality and oxidative stability of
ground chicken leg during display storage. Two hundred and forty, 1-day-old male
chicks (5 birds per pen) were subjected to four treatments in a 2 (thermoneutral
condition at 21 degrees C and cyclic heat stress at 32-21-32 degrees C for 10 h
day-1 ) * 2 (regular diet with 0 or 0.25 g kg-1 Bacillus subtilis) factorial
design. Chickens were harvested at day 46, and pairs of whole legs were collected
at 1 day postmortem. The chicken legs were deboned, ground, tray-packaged with
oxygen-permeable film, and displayed for 3 days. RESULTS: Heat stress and
probiotic supplementation had no impact on pH, water-holding capacity, color,
protein functionality, lipid lipolysis and lipid/protein oxidation stability (P >
0.05). Display storage increased the pH and lipid oxidation of ground chicken
legs (P < 0.05). In addition, protein oxidation occurred during display storage,
as determined via an increased carbonyl group (P = 0.0109) and reduced thiol
group (P < 0.0001). CONCLUSION: The results of the present study indicate that
chronic heat stress and probiotic supplementation had no practical adverse impact
on protein functionality and oxidative stability of ground chicken leg meat. (c)
2017 Society of Chemical Industry.
PMID- 28493473
TI - Dysregulation of mitochondrial bioenergetics and quality control by HIV-1 Tat in
cardiomyocytes.
AB - Cardiovascular disease remains a leading cause of morbidity and mortality in HIV
positive patients, even in those whose viral loads are well controlled with
antiretroviral therapy. However, the underlying molecular events responsible for
the development of cardiac disease in the setting of HIV remain unknown. The HIV
encoded Tat protein plays a critical role in the activation of HIV gene
expression and profoundly impacts homeostasis in both HIV-infected cells and
uninfected cells that have taken up released Tat via a bystander effect. Since
cardiomyocyte function, including excitation-contraction coupling, greatly
depends on energy provided by the mitochondria, in this study, we performed a
series of experiments to assess the impact of Tat on mitochondrial function and
bioenergetics pathways in a primary cell culture model derived from neonatal rat
ventricular cardiomyocytes (NRVCs). Our results show that the presence of Tat in
cardiomyocytes is accompanied by a decrease in oxidative phosphorylation, a
decline in the levels of ATP, and an accumulation of reactive oxygen species
(ROS). Tat impairs the uptake of mitochondrial Ca2+ ([Ca2+ ]m ) and the
electrophysiological activity of cardiomyocytes. Tat also affects the protein
clearance pathway and autophagy in cardiomyocytes under stress due to hypoxia
reoxygenation conditions. A reduction in the level of ubiquitin along with
dysregulated degradation of autophagy proteins including SQSTM1/p62 and a
reduction of LC3 II were detected in cardiomyocytes harboring Tat. These results
suggest that, by targeting mitochondria and protein quality control, Tat
significantly impacts bioenergetics and autophagy resulting in dysregulation of
cardiomyocyte health and homeostasis.
PMID- 28493475
TI - Change of left ventricular "rigid body rotation" during dipyridamole-induced
vasodilation: A case from the three-dimensional speckle tracking
echocardiographic MAGYAR-Stress Study.
AB - A patient with previous coronary stenting presented with stable angina and
positive exercise treadmill test. Echocardiography with three-dimensional speckle
tracking demonstrated left ventricular rigid body rotation (near absence of left
ventricular twist), whose characteristics changed dramatically during
dipyridamole-induced vasodilatation. (c) 2017 Wiley Periodicals, Inc. J Clin
Ultrasound 46:152-156, 2018.
PMID- 28493476
TI - First report on free and covalently bound microcystins in fish and bivalves from
Vietnam: Assessment of risks to humans.
AB - The free and covalently bound microcystins (MCs) in 3 fish and 2 bivalves from
the Dau Tieng Reservoir in Vietnam were investigated for the first time in the
present study. The results showed that all species were contaminated with MCs.
Our findings indicate that eating the muscle of fish from the Dau Tieng Reservoir
is safe but that eating the bivalves is not safe during toxic cyanobacterial
bloom episodes. Environ Toxicol Chem 2017;36:2953-2957. (c) 2017 SETAC.
PMID- 28493477
TI - Superficial basal cell carcinoma: A comparison of superficial only subtype with
superficial combined with other subtypes by age, sex and anatomic site in 3150
cases.
AB - BACKGROUND: Basal cell carcinoma (BCC) may present as superficial subtype alone
(sBCC) or superficial combined with other subtypes. The objective of this study
was to compare sBCC without or with other BCC subtypes by age, sex and anatomic
site. METHODS: We retrospectively collected superficial BCC with the above
characteristics from an Australian center during 2009 to 2014. RESULTS: We
recorded 1528 sBCC and 1622 superficial BCC combined with other BCC subtype
cases. Males numbered 2007 and females 1140. On males, head sites (forehead,
cheek, nose and ear combined) compared to limb plus trunk sites displayed a
higher incidence of superficial BCC combined with either nodular and or
aggressive BCC subtypes (OR 13.15 CI 95% 8.9-19.5 P < .0001). On females a
similar comparison also found a higher incidence of superficial BCC combined with
solid subtype BCC on head sites compared to trunk and limb sites (OR 9.66 CI 95%
5.8-16.1 P < .0001). CONCLUSION: Superficial BCC alone is more likely on younger
females on trunk and limb sites. Small partial biopsies reported as sBCC may miss
other BCC subtypes present with higher risk on facial sites for males and
females. Males had smaller proportions of superficial only subtype BCC on facial
and ear sites compared to females.
PMID- 28493478
TI - Three-dimensional models of the segmented human fetal brain generated by magnetic
resonance imaging.
AB - Recent advances in imaging technology have enabled us to obtain more detailed
images of the human fetus in a nondestructive and noninvasive manner. Through
detailed images, elaborate three-dimensional (3D) models of the developing brain
can be reconstructed. The segmentation of the developing brain has been
determined by serial sections. Therefore, in this study, we attempted to develop
a 3D model of the fetal brain using magnetic resonance image (MRI). MR images
from 19 specimens (11 embryonic specimens and eight fetal specimens from 5.2 to
225 mm in crown rump length) were used to reconstruct 3D models of regionalized
developing brains. From this analysis, we succeeded in registering a maximum of
nine landmarks on MR images and reconstructing 19 sequential models of the
regionalized developing brain. To confirm the validity of the landmarks, we also
compared our results with three serial sections from the Kyoto Collection; the
same morphological characteristics were observed on both serial sections and MRI.
The morphological minutiae could be found on MR images, and regionalized models
of the developing brain could be reconstructed. These results will be useful for
clinical diagnosis of living fetuses in utero.
PMID- 28493479
TI - Expectancies mediate the relationship between perceived injustice and return to
work following whiplash injury: A 1-year prospective study.
AB - BACKGROUND: Emerging evidence suggests that perceived injustice is a risk factor
for work disability in individuals with whiplash injury. At present, however,
little is known about the processes by which perceived injustice impacts on
return to work. The purpose of this study was to examine whether expectancies
mediated the relationship between perceived injustice and return to work in
patients with whiplash injury. METHOD: One hundred and fifty-two individuals (81
men, 71 women) with a primary diagnosis of whiplash injury completed self-report
measures of pain intensity, perceived injustice and return-to-work expectancies
following admission to a rehabilitation programme. Work status was assessed 1
year after discharge. RESULTS: Consistent with previous research, high scores on
a measure of perceived injustice were associated with prolonged work disability.
Results indicated that high perceptions of injustice were associated with low
return-to-work expectancies. Causal mediation analyses revealed that expectancies
fully mediated the relationship between perceived injustice and return to work.
CONCLUSION: The findings suggest that intervention techniques designed to target
expectancies could improve return-to-work outcomes in patients with whiplash
injury. Discussion addresses the processes by which expectancies might impact on
return-to-work outcomes and the manner in which negative return-to-work
expectancies might be modified through intervention. SIGNIFICANCE: The study
confirms that expectancies are the mechanism through which perceived injustice
impacts return to work following whiplash injury. The findings suggest that
interventions designed to specifically target return-to-work expectancies might
improve rehabilitation outcomes in patients with whiplash injury.
PMID- 28493480
TI - Sonographic findings of IgG4-related disease of the salivary glands: Case report
and review of the literature.
AB - IgG4-related disease is a relatively newly described entity with findings that
historically have been confused with a variety of other diseases with markedly
different treatments and prognoses, including Sjogren's syndrome and MALT
lymphoma. We present a case of IgG4-related disease of the salivary glands and
review the literature on sonographic findings of IgG4-related disease. By
connecting sonographic features of IgG4 disease with common ancillary features of
IgG4 disease in other sites (pancreas, hilar lymph nodes, biliary tree, thyroid,
and retroperitoneum), radiologists can play a pivotal role in the early diagnosis
and identification of IgG4-related disease. (c) 2017 Wiley Periodicals, Inc. J
Clin Ultrasound 46:73-77, 2018.
PMID- 28493481
TI - Hospital and Health Insurance Markets Concentration and Inpatient Hospital
Transaction Prices in the U.S. Health Care Market.
AB - OBJECTIVE: To examine the effects of hospital and insurer markets concentration
on transaction prices for inpatient hospital services. DATA SOURCES: Measures of
hospital and insurer markets concentration derived from American Hospital
Association and HealthLeaders-InterStudy data are linked to 2005-2008 inpatient
administrative data from Truven Health MarketScan Databases. STUDY DESIGN: Uses a
reduced-form price equation, controlling for cost and demand shifters and
accounting for possible endogeneity of market concentration using instrumental
variables (IV) technique. PRINCIPAL FINDINGS: The findings suggest that greater
hospital concentration raises prices, whereas greater insurer concentration
depresses prices. A hypothetical merger between two of five equally sized
hospitals is estimated to increase hospital prices by about 9 percent (p < .001).
A similar merger of insurers would depress prices by about 15.3 percent (p <
.001). Over the 2003-2008 periods, the estimates imply that hospital
consolidation likely raised prices by about 2.6 percent, while insurer
consolidation depressed prices by about 10.8 percent. Additional analysis using
longer panel data and applying hospital fixed effects confirms the impact of
hospital concentration on prices. CONCLUSION: The findings provide support for
strong antitrust enforcement to curb rising hospital service prices and health
care costs.
PMID- 28493483
TI - Preoperative imaging and prediction of oesophageal conduit necrosis after
oesophagectomy for cancer.
AB - BACKGROUND: Oesophageal conduit necrosis following oesophagectomy is a rare but
life-threatening complication. The present study aimed to assess the impact of
coeliac axis stenosis on outcomes after oesophagectomy for cancer. METHODS: The
study included consecutive patients who had an Ivor Lewis procedure with curative
intent for middle- and lower-third oesophageal cancer at two tertiary referral
centres. All patients underwent preoperative multidetector CT with arterial phase
to detect coeliac axis stenosis. The coeliac artery was classified as normal,
with extrinsic stenosis due to a median arcuate ligament or with intrinsic
stenosis caused by atherosclerosis. RESULTS: Some 481 patients underwent an Ivor
Lewis procedure. Of these, ten (2.1 per cent) developed oesophageal conduit
necrosis after surgery. Coeliac artery evaluation revealed a completely normal
artery in 431 patients (91.5 per cent) in the group without conduit necrosis and
in one (10 per cent) with necrosis (P < 0.001). Extrinsic stenosis of the coeliac
artery due to a median arcuate ligament was found in two patients (0.4 per cent)
without conduit necrosis and five (50 per cent) with necrosis (P < 0.001).
Intrinsic stenosis of the coeliac artery was found in 11 (2.3 per cent) and eight
(80 per cent) patients respectively (P < 0.001). Eight patients without (1.7 per
cent) and five (50 per cent) with conduit necrosis had a single and thin left
gastric artery (P < 0.001). CONCLUSION: This study suggests that oesophageal
conduit necrosis after oesophagectomy for cancer may be due to pre-existing
coeliac axis stenosis.
PMID- 28493482
TI - Emergence of cytochrome bc complexes in the context of photosynthesis.
AB - The cytochrome bc (cyt bc) complexes are involved in Q-cycling; they oxidize
membrane quinols by high-potential electron acceptors, such as cytochromes or
plastocyanin, and generate transmembrane proton gradient. In several prokaryotic
lineages, and also in plant chloroplasts, the catalytic core of the cyt bc
complexes is built of a four-helical cytochrome b (cyt b) that contains three
hemes, a three-helical subunit IV, and an iron-sulfur Rieske protein (cytochrome
b6 f-type complexes). In other prokaryotic lineages, and also in mitochondria,
the cyt b subunit is fused with subunit IV, yielding a seven- or eight-helical
cyt b with only two hemes (cyt bc1 -type complexes). Here we present an updated
phylogenomic analysis of the cyt b subunits of cyt bc complexes. This analysis
provides further support to our earlier suggestion that (1) the ancestral version
of cyt bc complex contained a small four-helical cyt b with three hemes similar
to the plant cytochrome b6 and (2) independent fusion events led to the formation
of large cyts b in several lineages. In the search for a primordial function for
the ancestral cyt bc complex, we address the intimate connection between the cyt
bc complexes and photosynthesis. Indeed, the Q-cycle turnover in the cyt bc
complexes demands high-potential electron acceptors. Before the Great Oxygenation
Event, the biosphere had been highly reduced, so high-potential electron
acceptors could only be generated upon light-driven charge separation. It appears
that an ancestral cyt bc complex capable of Q-cycling has emerged in conjunction
with the (bacterio)chlorophyll-based photosynthetic systems that continuously
generated electron vacancies at the oxidized (bacterio)chlorophyll molecules.
PMID- 28493485
TI - Comprehensive characterization of the acute and chronic toxicity of the
neonicotinoid insecticide thiamethoxam to a suite of aquatic primary producers,
invertebrates, and fish.
AB - Thiamethoxam is a neonicotinoid insecticide used widely in agriculture to control
a broad spectrum of chewing and sucking insect pests. Recent detection of
thiamethoxam in surface waters has raised interest in characterizing the
potential impacts of this insecticide to aquatic organisms. We report the results
of toxicity testing (acute and chronic) conducted under good laboratory practices
for more than 30 freshwater species (insects, molluscs, crustaceans, algae,
macrophytes, and fish) and 4 marine species (an alga, a mollusc, a crustacean,
and a fish). As would be anticipated for a neonicotinoid, aquatic primary
producers and fish were the least sensitive organisms tested, with acute median
lethal and effect concentrations (LC50/EC50) observed to be >=80 mg/L in all
cases, which far exceeds surface water exposure concentrations. Tested molluscs,
worms, and rotifers were similarly insensitive (EC50 >= 100 mg/L), except for
Lumbriculus sp., with an EC50 of 7.7 mg/L. In general, insects were the most
sensitive group in the study, with most acute EC50 values < 1 mg/L. However, the
crustaceans Asellus aquaticus and Ostracoda exhibited a sensitivity similar to
that of insects (acute EC50 < 1 mg/L), and the midge larvae Chaoborus sp. were
relatively insensitive compared with other insects (EC50 > 5.5 mg/L). The most
sensitive chronic response was for Chironomus riparius, with a 30-d no-observed
effect concentration (NOEC; emergence) of 0.01 mg/L. Observed toxicity to the
tested marine organisms was comparable to that of freshwater species. We used the
reported data to construct species sensitivity distributions for thiamethoxam, to
calculate 5% hazard concentrations (HC5s) for acute data (freshwater
invertebrates), and compared these with measured concentrations from relevant
North American surface waters. Overall, based on acute toxicity endpoints, the
potential acute risk to freshwater organisms was found to be minimal (likelihood
of exceeding HC5s < 1%). Environ Toxicol Chem 2017;36:2838-2848. (c) 2017 The
Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals,
Inc. on behalf of SETAC.
PMID- 28493484
TI - Cytoplasmic overexpression of RNA-binding protein HuR is a marker of poor
prognosis in meningioma, and HuR knockdown decreases meningioma cell growth and
resistance to hypoxia.
AB - HuR regulates cytoplasmic mRNA stability and translatability, and the HuR
expression level has been shown to correlate with poor disease outcome in several
cancer types; however, the prognostic value and potential pro-oncogenic
properties of HuR in meningioma remain unclear. Thus, in the present study, we
analysed 85 meningioma tissue samples to establish the relationship between HuR
expression, tumour cell proliferation, and/or patient survival. In addition, we
examined the anti-proliferative effects of HuR knockdown in two meningioma cell
lines (IOMM-Lee and Ben-Men-1) and conducted transcriptome-wide analyses (IOMM
Lee cells) to elucidate the molecular consequences of HuR knockdown. The results
of the present study showed HuR cytoplasmic expression to correlate positively
with tumour grade (p = 1.2 * 10-8 ) and negatively with progression-free and
overall survival (p = 0.01) time in human meningioma tissues. In vitro, siHuR
induced HuR knockdown was shown to reduce the growth of both Ben-Men-1 (p = 2 *
10-8 ) and IOMM-Lee (p = 4 * 10-9 ) cells. Transcriptome analyses revealed HuR
knockdown in IOMM-Lee cells to deregulate the HIF1A signalling pathway (p = 1.5 *
10-6 ) and to up-regulate the expression of genes essential for the assembly of
the cytoplasmic mRNA processing body, global genome nucleotide-excision repair,
poly(A)-specific ribonuclease activity, the positive regulation of apoptosis and
of cell cycle arrest, and the negative regulation of RNA splicing [p(FDR) <
0.001]. Interestingly, HuR knockdown under hypoxic culture conditions further
potentiated the effects of HuR knockdown on cell growth, apoptosis, and HIF1A
expression. We thus conclude that cytoplasmic HuR expression is a marker of poor
prognosis in meningioma and that HuR is a promising potential therapeutic target
for use in tumours refractory to standard therapies. Copyright (c) 2017
Pathological Society of Great Britain and Ireland. Published by John Wiley &
Sons, Ltd.
PMID- 28493486
TI - Pansteatitis in polluted Olifants River impoundments: nutritional perspectives on
fish in a eutrophic lake, Lake Loskop, South Africa.
AB - This study compares the aetiology of pansteatitis in Lake Loskop, relative to two
other impoundments along the Olifants River. Macroscopic and microscopic
pathology, age determination and analysis of stomach content, fatty acids and
stable isotopes explain the high prevalence of pansteatitis in Oreochromis
mossambicus (Peters) and several other species in Lake Loskop. All the dietary
indicator comparisons between pansteatitis-affected and healthy fish fail to
support a systemic cause. Pansteatitis in Lake Loskop was linked to size and
weight of O. mossambicus, but not to ontogenic age. Fish in Lake Loskop showed
abnormally high omega-3 to omega-6 fatty acid ratios normally only found in
marine fish with no significant difference in degree of assimilation of these
fatty acids between pansteatitis-affected and healthy fish. This explains the
vulnerability to, but not the occurrence of, pansteatitis. As a cause for the
pansteatitis, these results point towards sporadic vitamin E-depleting trigger
events, known sporadic fish die-off occurrences that provide surviving fish with
a rich source of rancid fats on which to scavenge. The mechanism ties
pansteatitis to eutrophication and trophic cascade effects, the intrinsic drivers
of the disease and suggests an adaptive management strategy that might be applied
by relevant conservation authorities.
PMID- 28493487
TI - Effect of starvation and refeeding on the hepatopancreas of whiteleg shrimp
Penaeus vannamei (Boone) using computer-assisted image analysis.
AB - Under normal farming conditions, shrimp can experience starvation periods
attributable to disease outbreaks or adverse environmental conditions. Starvation
leads to significant morphological changes in the hepatopancreas (HP), being the
main organ for absorption and storage of nutrients. In the literature, limited
research has described the effect on the HP of periods of starvation followed by
refeeding and none in whiteleg shrimp (Penaeus vannamei) using computer-assisted
image analysis (CAIA). This study describes the effect of starvation and
starvation followed by refeeding on the HP of whiteleg shrimp using CAIA.
Visiopharm(r) software was used to quantify the following morphological
parameters, measured as ratio to the total tissue area (TLA): total lumen area
(TLA:TTA), haemocytic infiltration area in the intertubular spaces (HIA:TTA), B
cell vacuole area (VBA:TTA), lipid droplet area within R cells (LDA:TTA) and F
cell area (FCA:TTA). Significant changes were measured for HIA:TTA and LDA:TTA
during starvation (increase in HIA:TTA associated with decrease in LDA:TTA) and
starvation followed by refeeding (decrease in HIA:TTA associated with increase in
LDA:TTA). In the future, HIA:TTA and LDA:TTA have the potential to be used in a
pre-emptive manner to monitor the health of the HP, facilitate early diagnosis of
diseases and study the pathophysiology of the organ.
PMID- 28493488
TI - Seasonality of odonate-mediated methylmercury flux from permanent and
semipermanent ponds and potential risk to red-winged blackbirds (Agelaius
phoeniceus).
AB - Methylmercury (MeHg) is an aquatic contaminant that can be transferred to
terrestrial predators by emergent aquatic insects such as odonates (damselflies
and dragonflies). We assessed the effects of month and pond permanence on odonate
mediated MeHg flux (calculated as emergent odonate biomass * MeHg concentration)
in 10 experimental ponds and the potential risk to nestling red-winged blackbirds
(Agelaius phoeniceus) posed by consuming MeHg-contaminated odonates. Emergent
odonates were collected weekly from permanent ponds with bluegill (Lepomis
macrochirus; n = 5) and semipermanent ponds without fish (n = 5) over an 8-mo
period (January-August 2015). The MeHg flux from damselflies, aeshnid
dragonflies, and libellulid dragonflies began in March and peaked in April, May,
and June, respectively, and then declined throughout the rest of the summer.
Odonate-mediated MeHg flux from semipermanent ponds without fish was greater than
that from permanent ponds with fish. Nesting of red-winged blackbirds overlapped
with peak odonate emergence and odonate-mediated MeHg flux. Because their diet
can be dominated by damselflies and dragonflies, we tested the hypothesis that
MeHg-contaminated odonates may pose a health risk to nestling red-winged
blackbirds. Concentrations of MeHg in odonates exceeded wildlife values (the
minimum odonate MeHg concentrations causing physiologically significant doses in
consumers) for nestlings, suggesting that MeHg-contaminated odonates can pose a
health risk to nestling red-winged blackbirds. Environ Toxicol Chem 2017;36:2833
2837. (c) 2017 SETAC.
PMID- 28493490
TI - The protective effect of humic-rich substances on atypical Aeromonas salmonicida
subsp. salmonicida infection in common carp (Cyprinus carpio L.).
AB - When challenged with atypical Aeromonas salmonicida subsp. salmonicida, exposure
of the common carp (Cyprinus carpio L.) to different humic-rich compounds
resulted in a significant reduction in infection rates. Specifically, in fish
exposed to (i) humic-rich water and sludge from a recirculating system, (ii) a
synthetic humic acid, and (iii) a Leonardite-derived humic-rich extract,
infection rates were reduced to 14.9%, 17.0% and 18.8%, respectively, as compared
to a 46.8% infection rate in the control treatment. An additional set of
experiments was performed to examine the effect of humic-rich components on the
growth of the bacterial pathogen. Liquid culture medium supplemented with either
humic-rich water from the recirculating system, the synthetic humic acid or the
Leonardite humic-rich extract resulted in a growth reduction of 41.1%, 45.2% and
61.6%, respectively, as compared to the growth of the Aeromonas strain in medium
devoid of humic substances. Finally, in a third set of experiments it was found
that while the innate immune system of the carps was not affected by their
exposure to humic-rich substances, their acquired immune system was affected.
Fish, immunized against bovine serum albumin, displayed elevated antibody titres
as compared to immunized carps which were not exposed to the various sources of
humic substances.
PMID- 28493489
TI - A path model of different forms of impulsivity with externalizing and
internalizing psychopathology: Towards greater specificity.
AB - OBJECTIVES: A growing empirical literature indicates that emotion-related
impulsivity (compared to impulsivity that is unrelated to emotion) is
particularly relevant for understanding a broad range of psychopathologies.
Recent work, however, has differentiated two forms of emotion-related
impulsivity: A factor termed Pervasive Influence of Feelings captures tendencies
for emotions (mostly negative emotions) to quickly shape thoughts, and a factor
termed Feelings Trigger Action captures tendencies for positive and negative
emotions to quickly and reflexively shape behaviour and speech. This study used
path modelling to consider links from emotion-related and non-emotion-related
impulsivity to a broad range of psychopathologies. DESIGN AND METHODS:
Undergraduates completed self-report measures of impulsivity, depression,
anxiety, aggression, and substance use symptoms. RESULTS: A path model (N = 261)
indicated specificity of these forms of impulsivity. Pervasive Influence of
Feelings was related to anxiety and depression, whereas Feelings Trigger Action
and non-emotion-related impulsivity were related to aggression and substance use.
CONCLUSIONS: The findings of this study suggest that emotion-relevant impulsivity
could be a potentially important treatment target for a set of psychopathologies.
PRACTITIONER POINTS: Recent work has differentiated two forms of emotion-related
impulsivity. This study tests a multivariate path model linking emotion-related
and non-emotion-related impulsivity with multiple forms of psychopathology.
Impulsive thoughts in response to negative emotions were related to anxiety and
depression. Impulsive actions in response to emotions were related to aggression
and substance use, as did non-emotion-related impulsivity. The study was limited
by the reliance on self-report measures of impulsivity and psychopathology. There
is a need for longitudinal work on how these forms of impulsivity predict the
onset and course of psychopathology.
PMID- 28493491
TI - High doses of recombinant mannan-binding lectin inhibit the binding of influenza
A(H1N1)pdm09 virus with cells expressing DC-SIGN.
AB - The pandemic influenza A (H1N1)pdm09 virus continues to be a threat to human
health. Low doses of mannan-binding lectin (MBL) (<1 MUg/mL) were shown not to
protect against influenza A(H1N1)pdm09 infection. However, the effect of high
doses of MBL has not been investigated. Dendritic cell-specific intercellular
adhesion molecule-3 grabbing non-integrin (DC-SIGN) has been proposed as an
alternative receptor for influenza A(H1N1)pdm09 virus. In this study, we examined
the expression of DC-SIGN on DCs as well as on acute monocytic leukemia cell
line, THP-1. High doses of recombinant or human MBL inhibited binding of
influenza A(H1N1)pdm09 to both these cell types in the presence of complement
derived from bovine serum. Further, anti-DC-SIGN monoclonal antibody inhibited
binding of influenza A(H1N1)pdm09 to both DC-SIGN-expressing DCs and THP-1 cells.
This study demonstrates that high doses of MBL can inhibit binding of influenza
A(H1N1)pdm09 virus to DC-SIGN-expressing cells in the presence of complement. Our
results suggest that DC-SIGN may be an alternative receptor for influenza
A(H1N1)pdm09 virus.
PMID- 28493492
TI - Dehydroacetic Acid Derivatives Bearing Amide or Urea Moieties as Effective Anion
Receptors.
AB - Derivatives of dehydroacetic acid comprising amide or urea subunits have been
synthesized and their anion-binding properties investigated. Among a series of
halides and oxyanions, the studied compounds selectively bind acetate and
dihydrogen phosphate in acetonitrile and dimethyl sulfoxide. The corresponding
complexation processes were characterized by means of 1 H NMR titrations, which
revealed a 1:1 complex stoichiometry in most cases, with the exception of
dihydrogen phosphate, which formed 2:1 (anion/ligand) complexes in acetonitrile.
The complex stability constants were determined and are discussed with respect to
the structural properties of the receptors, the hydrogen-bond-forming potential
of the anions, and the characteristics of the solvents used. Based on the
spectroscopic data and results of Monte Carlo simulations, the amide or urea
groups were affirmed as the primary binding sites in all cases. The results of
the computational methods indicate that an array of both inter- and
intramolecular hydrogen bonds can form in the studied systems, and these were
shown to play an important role in defining the overall stability of the
complexes. Solubility measurements were carried out in both solvents and the
thermodynamics of transfer from acetonitrile to dimethyl sulfoxide were
characterized on a quantitative level. This has afforded a detailed insight into
the impact of the medium on the complexation reactions.
PMID- 28493493
TI - Neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and mean platelet volume
in Japanese patients with psoriasis and psoriatic arthritis: Response to therapy
with biologics.
AB - Recent studies indicate the presence of systemic inflammation in psoriatic
patients, and this inflammatory status is significantly associated with a range
of comorbidities. The aim of this study was to evaluate the clinical significance
of novel inflammatory biomarkers, neutrophil-lymphocyte ratio (NLR), platelet
lymphocyte ratio (PLR) and mean platelet volume (MPV) in Japanese patients with
plaque-type psoriasis (PsV) and psoriatic arthritis (PsA). One hundred and eighty
six patients with PsV and 50 patients with PsA treated with biologics, including
infliximab, adalimumab and ustekinumab, were retrospectively analyzed before and
after treatment. At baseline, NLR and PLR, as well as C-reactive protein (CRP),
were significantly higher in PsA patients than those in PsV patients, and a
significant correlation was found between NLR and PLR. In PsV patients, the NLR
high and PLR-high subgroups exhibited significantly higher Psoriasis Area and
Severity Index scores compared with the NLR-low and PLR-low subgroups,
respectively, and the NLR-high subgroup also showed higher CRP levels. MPV value
was negatively associated with the presence of arthritis, but its association
with inflammation was less clear than that of NLR or PLR. After treatment of the
patients with biologics for up to 12 months, NLR and PLR decreased promptly in
parallel with a decrease of CRP, irrespective of the type of biologics used.
Altogether, these results indicate that both NLR and PLR may be useful markers to
evaluate systemic inflammation in psoriatic patients. They may serve as simple,
convenient and cost-effective biomarkers to monitor the disease course after
systemic therapy.
PMID- 28493494
TI - STAT3 promotes bone fracture healing by enhancing the FOXP3 expression and the
suppressive function of regulatory T cells.
AB - Signal transducer and activator of transcription 3 (STAT3) is a key signaling
protein in the skeletal system as well as in the immune system. Accumulating
evidence demonstrates that the inflammatory response is deeply involved in the
healing process of bone fractures, but how the immune system is regulated during
this process is unclear. In this study, we examined STAT3-mediated regulation of
immunity in adult patients with closed tibia fracture. In all patients, the
expression and activation of STAT3 peaked at around day 7 to day 14 after
surgery, and gradually decreased during the rest of the healing period. At day 7
(peak STAT3 expression and phosphorylation), the CD4+ CD25+ T cells from bone
fracture patients presented the highest level of STAT3 activation among
lymphocyte subsets. Therefore, we investigated the role of STAT3 in CD4+ CD25+ T
cells. The level of FOXP3 expression by CD4+ CD25+ T cells was directly
correlated with the level of STAT3 phosphorylation in these cells. The level of
STAT3 phosphorylation in CD4+ CD25+ T cells was also inversely correlated with
the level of IFN-gamma and TNF-alpha secretion in peripheral blood mononuclear
cells. Inhibition of STAT3 significantly suppressed FOXP3 and IL-10 expression by
CD4+ CD25+ T cells, as well as the ability of CD4+ CD25+ T cells to suppress T
cell IFN-gamma and TNF-alpha secretion. Furthermore, early healers patients
presented significantly higher STAT3 expression and phosphorylation than late
healers, possibly due to the higher IL-6 and IL-10 levels in the serum of early
healing patients. Together, these data demonstrated that STAT3 was beneficial to
bone fracture healing, possibly by enhancing Treg-mediated suppression of
counteracting inflammations, and suggested that STAT3 could be used as a
prognostic marker to identify otherwise undistinguishable patients at risk of
developing delayed union or nonunion.
PMID- 28493495
TI - Silver-Catalyzed Three-Component 1,1-Aminoacylation of Homopropargylamines: alpha
Additions for Both Terminal Alkynes and Isocyanides.
AB - The reaction of secondary homopropargylamines, isocyanides, and water in the
presence of a catalytic amount of silver acetate and subsequent purification by
chromatography on silica gel afforded substituted proline amides in good to
excellent yields. Primary homopropargylamines underwent a cyclizative Ugi-Joullie
three-component reaction with isocyanides and carboxylic acids to afford
functionalized N-acyl proline amides. High diastereoselectivity was observed in
the synthesis of 4-alkoxy and 4,5-disubstituted proline derivatives. This work
represents the first examples of a three-component cyclizative 1,1-aminoacylation
of terminal alkynes.
PMID- 28493496
TI - A New Potent Inhibitor of Glycogen Phosphorylase Reveals the Basicity of the
Catalytic Site.
AB - The design and synthesis of a glucose-based acridone derivative (GLAC), a potent
inhibitor of glycogen phosphorylase (GP) are described. GLAC is the first
inhibitor of glycogen phosphorylase, the electronic absorption properties of
which are clearly distinguishable from those of the enzyme. This allows probing
subtle interactions in the catalytic site. The GLAC absorption spectra,
associated with X-ray crystallography and quantum chemistry calculations, reveal
that part of the catalytic site of GP behaves as a highly basic environment in
which GLAC exists as a bis-anion. This is explained by water-bridged hydrogen
bonding interactions with specific catalytic site residues.
PMID- 28493497
TI - Coordination Behavior of [Cp''2 Zr(eta1:1 -P4 )] towards Different Lewis Acids.
AB - A detailed method for the preparation of [Cp''2 Zr(eta1:1 -P4 )] (1) is
presented. The coordination behavior of 1 towards Lewis acidic transition metal
complexes of tungsten, manganese, and iron, respectively, and main group
compounds (AlMe3 , AlEt3 ) was investigated in detail by computational and
experimental studies. In doing so, a series of unprecedented complexes with
different coordination modes and multiple coordination numbers of the
tetraphosphabicyclo[1.1.0]butane framework were synthesized. All products, as
well as the starting materials, were comprehensively characterized by NMR
spectroscopy, mass spectrometry, elemental analysis, and single crystal X-ray
structural analysis.
PMID- 28493498
TI - Endoscopic ultrasound-guided retrieval of a toothpick embedded in the stomach
wall.
AB - Patients with the complaint of ingested foreign body commonly present in the
emergency department. Radiographic imaging is always done for the purpose of
localization. However, radiolucent materials like wood are not easily picked up
on CT scan. We report the case of a 33-year-old male patient who presented with
the complaint of progressive abdominal pain and history of ingestion of a
toothpick. It was removed by endoscopic ultrasound-guided localization-assisted
targeted endoscopic dissection. Endoscopic ultrasound-guided localization reduced
the length and depth of the required incision and helped to minimize the risk of
damage to the surrounding tissue. (c) 2017 Wiley Periodicals, Inc. J Clin
Ultrasound 45:603-604, 2017.
PMID- 28493499
TI - Length-mass allometries in amphibians.
AB - Body mass is rarely recorded in amphibians, and other body measurements (e.g.
snout to vent length, SVL) are generally collected instead. However, length
measurements, when used as proxies of body mass in comparative analyses, are
problematic if different taxa and morphotypes are included. We developed
allometric relationships to derive body mass from SVL measurements. We fitted
phylogenetic generalized least square models for frogs (Anura) and salamanders
(Caudata) and for several families separately. We tested whether allometric
relationships differed between species with different habitat preferences and
between morphs in salamanders. Models were fitted with SVL-mass measurements for
88 frog and 42 salamander species. We assessed the predictive performance of the
models by cross-validation. Overall, the models showed high explained variance
and low forecasting errors. Models differed among semi-aquatic, terrestrial and
arboreal frogs, and between paedomorphic and non-paedomorphic salamanders. Body
mass estimates derived from our models allow for comparability of studies on
multiple taxa and can be used for testing theories built upon evolutionary and
ecological processes which are directly related to body mass.
PMID- 28493500
TI - Conformational Analysis of the Mannosidase Inhibitor Kifunensine: A Quantum
Mechanical and Structural Approach.
AB - The varied yet family-specific conformational pathways used by individual
glycoside hydrolases (GHs) offer a tantalising prospect for the design of tightly
binding and specific enzyme inhibitors. A cardinal example of a GH-family
specific inhibitor, and one that finds widespread practical use, is the natural
product kifunensine, which is a low-nanomolar inhibitor that is selective for GH
family 47 inverting alpha-mannosidases. Here we show, through quantum-mechanical
approaches, that kifunensine is restrained to a "ring-flipped" 1 C4 conformation
with another accessible, but higher-energy, region around the 1,4 B conformation.
The conformations of kifunensine in complex with a range of GH47 enzymes
including an atomic-level resolution (1 A) structure of kifunensine with
Caulobacter sp. CkGH47 reported herein and with GH family 38 and 92 alpha
mannosidases-were mapped onto the kifunensine free-energy landscape. These
studies revealed that kifunensine has the ability to mimic the product state of
GH47 enzymes but cannot mimic any conformational states relevant to the reaction
coordinate of mannosidases from other families.
PMID- 28493501
TI - Enzyme-Inspired Chiral Secondary-Phosphine-Oxide Ligand with Dual Noncovalent
Interactions for Asymmetric Hydrogenation.
AB - Inspired by the unique character of enzymes, we developed novel chiral SPO
(secondary-phosphine-oxide) ligand (SPO-Wudaphos) which can enter into both ion
pair and H-bond noncovalent interactions. The novel chiral SPO-Wudaphos exhibited
excellent results in the asymmetric hydrogenation of alpha-methylene-gamma-keto
carboxylic acids, affording the chiral gamma-keto acids with up to over 99 % ee.
A series of control experiments and DFT calculations were conducted to illustrate
the critical roles of both the ion pair and H-bond noncovalent interactions.
PMID- 28493502
TI - Fasiglifam for glycaemic control in people with type 2 diabetes: A phase III,
placebo-controlled study.
AB - AIM: To investigate the effect of fasiglifam on glycaemic control in people with
type 2 diabetes mellitus (T2DM). METHODS: In total, 421 people with T2DM and
glycated haemoglobin (HbA1c) >=7.0% and <=10.5% who had received only diet and
exercise treatment for >=12 weeks prior to screening were randomized to receive
fasiglifam 25 or 50 mg or placebo. The primary efficacy endpoint was change from
baseline in HbA1c at week 24. RESULTS: The mean participant age was 53.5 years,
mean baseline body mass index 32.3 kg/m2 , and mean baseline HbA1c level 8.05%.
Least squares mean changes in HbA1c from baseline to week 24 were: -0.93%
(fasiglifam 50 mg), -0.65% (fasiglifam 25 mg) and -0.17% (placebo). Treatment
emergent adverse events (TEAEs) occurred in 53.3%, 48.2% and 39.9% of
participants receiving fasiglifam 25 mg, fasiglifam 50 mg, and placebo,
respectively. Three participants in each group experienced a serious adverse
event (AE). Nine participants had alanine aminotransferase (ALT) elevations >3*
upper limit of normal: 5 (3.6%) in the fasiglifam 25-mg group, 4 (2.8%) in the
fasiglifam 50-mg group, and none in the placebo group. CONCLUSIONS: The data
indicate that fasiglifam effectively reduced HbA1c from baseline for 24 weeks in
participants with T2DM. The incidence of TEAEs was higher in the fasiglifam
groups; however, the incidence of serious AEs was low overall and similar between
groups. ALT elevations were observed only in the fasiglifam groups, which
contributed to the decision to terminate the fasiglifam programme after
completion of the present study.
PMID- 28493503
TI - Liver of the fish Gymnotus inaequilabiatus and nematode larvae infection:
Histochemical features and expression of proliferative cell nuclear antigen.
AB - Histopathological lesions due to third-larval stage of nematode Brevimulticaecum
sp. within the liver of a subpopulation of 31 Gymnotus inaequilabiatus from the
Pantanal Region (Brazil) were studied with histochemical and immunohistochemical
methods. In 93.5% of fish, livers harboured nematode larvae and the intensity of
infection ranged from 8 to 293. In livers with highest number of larvae, the
hepatic tissue was occupied primarily by the nematodes. Each larva was encircled
by focal inflammatory granulomatous reaction. Within the thickness of the
granuloma, three concentric layers were recognized: an inner layer of densely
packed epithelioid cells, a middle layer of mast cells (MCs) entrapped in a thin
fibroblast-connective mesh and an outer layer of fibrous connective tissue with
fibroblasts. Epithelioid cells and fibroblasts within the thickness of the
granuloma wall were positive for proliferative cell nuclear antigen (PCNA).
Moreover, several hepatocytes in infected liver were immunoreactive to PCNA.
Occurrence of rodlet cells and MCs in parenchyma, in close proximity to the
encysted nematode larvae and near the blood vessel of infected liver, was
observed. Macrophage aggregates (MAs) were numerous within the granulomas and
scattered in parenchyma of the infected liver. High quantity of haemosiderin was
encountered in MAs and hepatocytes of infected liver.
PMID- 28493504
TI - Imaging sonographic findings of in a case of proliferating trichilemmal tumor of
a finger: A case report.
AB - Proliferating trichilemmal tumor (PTT) is a rare tumor that originates from the
outer root sheath of a hair follicle. About 90% of PTTs occur on the scalp. The
sonographic findings of PTT in the subungual region have not been reported
previously. In our case, sonography showed a heterogeneous mass containing
echogenic foci with no detectable intratumoral vascularity. These echogenic foci
probably represent keratin and cholesterol. (c) 2017 Wiley Periodicals, Inc. J
Clin Ultrasound 46:215-217, 2018.
PMID- 28493505
TI - Resilience in ecotoxicology: Toward a multiple equilibrium concept.
AB - The term resilience describes stress-response patterns across scientific
disciplines. In ecology, advances have been made to clearly define resilience
based on underlying mechanistic assumptions. Engineering resilience (rebound) is
used to describe the ability of organisms to recover from adverse conditions
(disturbances), which is termed the rate of recovery. By contrast, the ecological
resilience definition considers a systemic change, that is, when ecosystems
reorganize into a new regime following disturbance. Under this new regime,
structural and functional aspects change considerably relative to the previous
regime, without recovery. In this context, resilience is an emergent property of
complex systems. In the present study, we argue that both definitions and uses
are appropriate in ecotoxicology, and although the differences are subtle, the
implications and uses are profoundly different. We discuss resilience concepts in
ecotoxicology, where the prevailing view of resilience is engineering resilience
from chemical stress. Ecological resilience may also be useful for describing
systemic ecological changes because of chemical stress. We present quantitative
methods that allow ecotoxicologists and risk managers to assess whether an
ecosystem faces an impending regime shift or whether it has already undergone
such a shift. We contend that engineering and ecological resilience help to
distinguish ecotoxicological responses to chemical stressors mechanistically and
thus have implications for theory, policy, and application. Environ Toxicol Chem
2017;36:2574-2580. (c) 2017 SETAC.
PMID- 28493506
TI - Alemtuzumab dose adjusted for body weight is associated with earlier lymphocyte
repletion and less infective episodes in the first year post renal
transplantation - a retrospective study.
AB - The optimal dose of alemtuzumab for renal transplant induction is not known, and
the doses reported in the literature vary. This study compares two separate
dosing regimens of alemtuzumab in renal transplantation. The first is a standard
fixed dose of 30 mg (SD), and the second is a dose adjusted for body weight at
0.4 mg/kg (AD). In this first year post-transplant, there was no difference in
patient [HR 0.64 (0.22-1.86), P = 0.39] or allograft survival [HR 1.18 (0.48
2.90), P = 0.72] between the two groups. There was also no difference in overall
rejection-free survival [HR 1.12 (0.79-1.58), P = 0.53]. However, absolute
lymphocyte count was significantly higher at all measured time points in the
first year in the AD group. There were also less episodes of urosepsis [HR 1.38
(1.03-1.85), P = 0.037] and fungal infection [HR 5.15 (2.00-13.28), P = 0.015] in
the AD group compared with the SD group. This study shows that AD alemtuzumab is
associated with earlier lymphocyte repletion and less infective episodes in the
first year postrenal transplant, without increasing the risk of rejection. This
work highlights the need for studies into the optimal dosing of monoclonal
antibodies used in transplantation.
PMID- 28493507
TI - PKC, ERK/p38 MAP kinases and NF-kappaB targeted signalling play a role in the
expression and release of IL-1beta and CXCL8 in Porphyromonas gingivalis-infected
THP1 cells.
AB - Porphyromonas gingivalis is a keystone pathogen in periodontitis and is gaining
importance in cardiovascular pathogenesis. Protease-activated receptors (PARs),
toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD) on
monocytes recognize the structural components on P. gingivalis, inducing
inflammatory intermediates. Here, we elucidate the modulation of PARs, TLRs,
NODs, and the role of MAPK and NF-kappaB in IL-1beta and CXCL8 release. THP1
cells were stimulated with P. gingivalis wild-type W50 and its isogenic gingipain
mutants: Rgp mutant E8 and Kgp mutant K1A. We observed modulation of PARs, TLRs,
NOD, IL-1beta and CXCL8 expression by P. gingivalis. Gingipains hydrolyse IL
1beta and CXCL8, which is more evident for IL-1beta accumulation at 24 h.
Inhibition of PKC (protein kinase C), p38 and ERK (extracellular signal-regulated
kinases) partially reduced P. gingivalis-induced IL-1beta at 6 h, whereas PKC and
ERK reduced CXCL8 at both 6 and 24 h. Following NF-kappaB inhibition, P.
gingivalis-induced IL-1beta and CXCL8 were completely suppressed to basal levels.
Overall, TLRs, PARs and NOD possibly act in synergy with PKC, MAPK ERK/p38 and NF
kappaB in P. gingivalis-induced IL-1beta and CXCL8 release from THP1 cells. These
pro-inflammatory cytokines could affect leucocytes in circulation and exacerbate
other vascular inflammatory conditions such as atherosclerosis.
PMID- 28493508
TI - Apgar Score Components at 5 Minutes: Risks and Prediction of Neonatal Mortality.
AB - BACKGROUND: The Apgar score consists of five components: heart rate, respiratory
effort, muscle tone, reflex irritability, and colour. Although the Apgar score
has been used for 60 years, the specific contribution of the Apgar score
components with respect to risks and prediction of neonatal mortality remains
unknown. Likewise, the value of reduced scores (including less than five Apgar
score components) has rarely been investigated. METHODS: In a population-based
cohort study of 148 765 liveborn singleton infants in Sweden 2008-2013, we
investigated components of Apgar score at 5 min with respect to relative risks
and prediction (using ROC curves, sensitivity, and positive predictive values) of
neonatal mortality. RESULTS: Reduced values (0-1) of heart rate, respiratory
effort, and colour were independently associated with increased relative risks of
neonatal mortality. For the full Apgar score, the sensitivity and positive
predictive values of neonatal mortality (cut-off <=3) were by gestational age:
<=31 weeks: 56.1% and 49.2%; 32-36 weeks: 25.0% and 18.2%; and >=37 weeks: 35.2%
and 9.3%, respectively. When only heart rate and respiratory effort were
considered (range 0-4; cut-off <=2), corresponding values were 66.7% and 34.9%;
37.5% and 13.0%; and 46.3% and 7.6%, respectively. CONCLUSIONS: A reduced Apgar
score has generally the same predictability of neonatal mortality as the full
Apgar score. The full Apgar score or reduced scores may be better predictors of
neonatal mortality in very preterm infants (<=31 weeks) than in infants with
longer gestations.
PMID- 28493509
TI - Linking public health nursing competencies and service-learning in a global
setting.
AB - BACKGROUND: Nurse educators in baccalaureate programs are charged with addressing
student competence in public health nursing practice. These educators are also
responsible for creating nursing student opportunities for civic engagement and
development of critical thinking skills. The IOM report (2010) on the Future of
Nursing emphasizes the nurse educator's role in promoting collaborative
partnerships that incorporate interdisciplinary and intraprofessional efforts to
promote health. AIM: The purpose of this article is to describe an innovative
approach to address public health nursing competencies and to improve the health
and well-being of indigenous populations in a global setting through promotion of
collaboration and service- learning principles. METHODS: As part of a hybrid
elective course, baccalaureate nursing students from various nursing tracks
participated in a 2 week immersion experience in Belize that included
preimmersion preparation. These students were to collaborate among themselves and
with Belizean communities to address identified health knowledge deficits and
health-related needs for school-aged children and adult populations. RESULTS:
Students successfully collaborated in order to meet health-related needs and to
engage in health promotion activities in the Toledo district of Belize. They also
gained practice in developing public health nursing competencies for entry-level
nursing practice. Implementation of service-learning principles provided students
with opportunities for civic engagement and self-reflection. DISCUSSION: Some
challenges existed from the students', faculty, and global community's
perspectives. Lack of culturally appropriate and country specific health
education materials was difficult for students and the community. Faculty
encountered challenges in communicating and collaborating with the Belizean
partners. CONCLUSION: Commonalities exist between entry-level public health
nursing competencies and service-learning principles. Using service-learning
principles in the development of public health experiences increases the
likelihood of success in achieving these competencies. While students
demonstrated intraprofessional collaboration in a global setting, these same
collaborative opportunities can occur in local communities.
PMID- 28493510
TI - Comparison of reversal with neostigmine of low-dose rocuronium vs. reversal with
sugammadex of high-dose rocuronium for a short procedure.
AB - Some short procedures require deep neuromuscular blockade, which needs to be
reversed at the end of the procedure. Forty-four patients undergoing elective
laryngeal micro-surgery were randomly allocated into two groups: rocuronium 0.45
mg.kg-1 with neostigmine (50 MUg.kg-1 with glycopyrrolate 10 MUg.kg-1 ) reversal
(moderate block group) vs. rocuronium 0.90 mg.kg-1 with sugammadex (4 mg.kg-1 )
reversal (deep block group). The primary outcome was the intubating conditions
during laryngoscopy secondary outcomes included recovery of neuromuscular block;
conditions for tracheal intubation; satisfaction score as determined by the
surgeon; onset of neuromuscular block; and postoperative sore throat. The onset
of neuromuscular block was more rapid, and intubation conditions and ease of
intra-operative laryngoscopy were more favourable, and the satisfaction score was
lower in the moderate block group compared with the deep block group. No
difference was found in the incidence of postoperative sore throat. In laryngeal
micro-surgery, the use of rocuronium 0.9 mg.kg-1 with sugammadex for reversal was
associated with better surgical conditions and a shorter recovery time than
rocuronium 0.45 mg.kg-1 with neostigmine.
PMID- 28493512
TI - Decreased expression of hsa_circ_0003570 in hepatocellular carcinoma and its
clinical significance.
AB - BACKGROUND: Circular RNAs (circRNAs) constitute a class of non-coding RNAs
recently discovered to be widespread and abundant in mammalian cells. However,
the expression features of most of circRNAs in hepatocellular carcinoma (HCC) are
unraveled. In this study, we focused on hsa_circ_0003570, which was found to be
down-regulated in HCC tissues in our previous microarray screening. METHODS: The
hsa_circ_0003570 levels in HCC cell lines, HepG2, SMMC-7721, MHCC97L, MHCC97H,
and HCCLM3, and human normal hepatic cell line L02 were detected by quantitative
reverse transcription-polymerase chain reaction (qRT-PCR). Then, its levels in
107 paired HCC tissues and adjacent non-tumor tissues, 60 liver biopsy samples
from patients with chronic liver diseases were detected by qRT-PCR. The receiver
operating characteristic curve (ROC) was used to evaluate the diagnostic value of
hsa_circ_0003570 for HCC. RESULTS: Hsa_circ_0003570 was not only first found down
regulated in HCC cell lines (P<.001) but also in HCC tissues (P<.001). Moreover,
hsa_circ_0003570 was gradually decreased from chronic hepatitis (CH), to liver
cirrhosis (LC) and to HCC tissues (P<.01). Its expression levels were
significantly correlated with tumor diameter (P=.035), differentiation (P=.013),
microvascular invasion (P=.045), Barcelona Clinic Liver Cancer stages (P=.011),
tumor-node-metastasis stages (P=.016), and serum alpha-fetoprotein levels
(P=.031). The ROC curve demonstrated that hsa_circ_0003570 had poor performance
for differentiating HCC from LC and CH, but had relatively good performance for
differentiating LC from CH. CONCLUSIONS: These results indicated that
hsa_circ_0003570 expression levels were associated with HCC clinicopathological
characteristics.
PMID- 28493511
TI - Direct endovascular treatment: an alternative for bridging therapy in anterior
circulation large-vessel occlusion stroke.
AB - BACKGROUND AND PURPOSE: Whether intravenous thrombolysis prior to endovascular
treatment in patients with anterior circulation large-vessel occlusion (LVO) is
indispensable remains unclear. The aim was to retrospectively compare, in a
Chinese population, the effectiveness and safety of direct endovascular treatment
(DEVT) initiated within 4.5 h after onset with bridging therapy in acute anterior
circulation LVO stroke patients. METHODS: A total of 363 patients, 160 in the
bridging therapy group and 203 in the DEVT group, were enrolled between 2014 and
2016. Using propensity score matching analysis, 276 patients were matched. A
modified Rankin Scale score of 0-2 was considered as good functional outcome.
RESULTS: Good functional outcome at 90 days in the DEVT group [40.6% (56/138)]
did not significantly differ from that in the bridging group [44.9% (62/138)] (P
= 0.53). Rates of symptomatic intracranial hemorrhage [13.8% (19/138) vs. 13.0%
(18/138), P = 1.00] and mortality [25.4% (35/138) vs. 23.9% (33/138), P = 0.88]
within 90 days were also not significantly different. Patients in the DEVT group
had a lower rate of asymptomatic intracranial hemorrhage [28.3% (39/138) vs.
44.9% (62/138), P = 0.01] and a higher rate of successful reperfusion [92.0%
(127/138) vs. 81.9% (113/138), P = 0.02]. CONCLUSIONS: Our results suggest that,
in Chinese patients with anterior circulation LVO stroke, direct endovascular
mechanical thrombectomy initiated within an intravenous thrombolysis time window
carries similar effectiveness to that of bridging therapy and a decreased
asymptomatic intracranial hemorrhage risk. DEVT may be an alternative for
bridging therapy. Future randomized controlled trials are warranted.
PMID- 28493513
TI - Metal-Free Poly-Cycloaddition of Activated Azide and Alkynes toward
Multifunctional Polytriazoles: Aggregation-Induced Emission, Explosive Detection,
Fluorescent Patterning, and Light Refraction.
AB - The metal-free click polymerization (MFCP) of activated alkynes and azides or
activated azide and alkynes have been developed into powerful techniques for the
construction of polytriazoles without the obsession of metallic catalyst residues
problem. However, the MFCP of activated azides and alkynes is rarely applied in
preparation of functional polytriazoles. In this paper, soluble multifunctional
polytriazoles (PIa and PIb) with high weight-average molecular weights (Mw up to
32 000) are prepared via the developed metal-free poly-cycloaddition of activated
azide and alkynes in high yields (up to 90%). The resultant PIa and PIb are
thermally stable, and show aggregation-induced emission characteristics, enabling
their aggregates to detect explosives with superamplification effect. Moreover,
thanks to their containing aromatic rings and polar moieties, PIa and PIb exhibit
high refractive indices. In addition, they can also be cross-linked upon UV
irradiation to generate 2D fluorescent patterning due to their remaining azide
groups and containing ester groups. Thus, these multifunctional polytriazoles are
potentially applicable in the optoelectronic and sensing fields.
PMID- 28493514
TI - Protective effect and antibody response of DNA vaccine against salmonid
alphavirus 3 (SAV3) in Atlantic salmon.
AB - This work reports the effect of two DNA vaccines against salmonid alphavirus 3
(SAV3) in Atlantic salmon. Presmolts were vaccinated by intramuscular injection
of plasmids encoding the SAV3 structural polyprotein C-E3-E2-6K-E2 (pCSP), E2
only (pE2), or plasmid without insert (pcDNA3.3). E2 is expressed at the surface
of cells transfected with pCSP and internally in cells transfected with pE2. A
commercial vaccine based on inactivated SAV (NCPD) was used for comparison. At 10
weeks post-vaccination, only fish vaccinated with pCSP showed antibody against E2
and virus-neutralizing activity. Vaccinated fish were infected with SAV3 to
determine protection by virus quantitation in serum after 7 days and scoring of
pathological changes after 21 days. Fish vaccinated with both pCSP and NCPD
vaccines showed significant virus reduction in serum, while fish vaccinated with
pE2 did not. All fish vaccinated with pcDNA3.3 and pE2 showed pathological
changes in organs typical of PD, 60% of fish vaccinated with NCPD showed PD
pathology, while fish vaccinated with pCSP did not show PD pathology. Taken
together, DNA vaccination with pCSP provided strong protection for salmon against
SAV3 infection, which in part may be due to production of virus-neutralizing
antibodies.
PMID- 28493516
TI - A Computational Study of a Single-Walled Carbon-Nanotube-Based Ultrafast High
Capacity Aluminum Battery.
AB - Exploring suitable electrode materials is a fundamental step toward developing Al
batteries with enhanced performance. In this work, we explore using density
functional theory calculations the feasibility of single-walled carbon nanotubes
(SWNTs) as a cathode material for Al batteries. Carbon nanotubes with hollow
structures and large surface area are able to overcome the difficulty of
activating the opening of interlayer spaces as observed in graphite electrode
during the first intercalation cycle. Our results show that AlCl4 binds strongly
with the SWNT to result in an energetically and thermally stable AlCl4 -adsorbed
SWNT system. Diffusion calculations show that the SWNT system allows ultrafast
diffusion of AlCl4 with a more favorable inner surface diffusion than outer
surface diffusion. Our charge-density difference and Bader atomic charge analysis
confirm the oxidation of SWNT upon adsorption of AlCl4 , which shows a similar
behavior to the previously studied graphite cathode. The average open-circuit
voltage and AlCl4 storage capacity increases with increasing SWNT diameter and
can be as high as 1.96 V and 275 mA h g-1 in (25,25) SWNT relative to graphite
(70 mA h g-1 ). All of these properties show that SWNTs are a potential cathode
material for high-performance Al batteries and should be explored further.
PMID- 28493515
TI - Review of methods for measuring beta-cell function: Design considerations from
the Restoring Insulin Secretion (RISE) Consortium.
AB - The Restoring Insulin Secretion (RISE) study was initiated to evaluate
interventions to slow or reverse the progression of beta-cell failure in type 2
diabetes (T2D). To design the RISE study, we undertook an evaluation of methods
for measurement of beta-cell function and changes in beta-cell function in
response to interventions. In the present paper, we review approaches for
measurement of beta-cell function, focusing on methodologic and feasibility
considerations. Methodologic considerations included: (1) the utility of each
technique for evaluating key aspects of beta-cell function (first- and second
phase insulin secretion, maximum insulin secretion, glucose sensitivity, incretin
effects) and (2) tactics for incorporating a measurement of insulin sensitivity
in order to adjust insulin secretion measures for insulin sensitivity
appropriately. Of particular concern were the capacity to measure beta-cell
function accurately in those with poor function, as is seen in established T2D,
and the capacity of each method for demonstrating treatment-induced changes in
beta-cell function. Feasibility considerations included: staff burden, including
time and required methodological expertise; participant burden, including time
and number of study visits; and ease of standardizing methods across a
multicentre consortium. After this evaluation, we selected a 2-day measurement
procedure, combining a 3-hour 75-g oral glucose tolerance test and a 2-stage
hyperglycaemic clamp procedure, augmented with arginine.
PMID- 28493517
TI - Clinicopathological analysis of primary splenic diffuse large B-cell lymphoma.
AB - Splenic infiltration is often seen in diffuse large B-cell lymphoma (DLBCL).
However, primary splenic DLBCL is rare and studies on its clinicopathological
features are limited. We assessed 66 cases of primary splenic DLBCL and 309
control DLBCL, not otherwise specified. Hepatitis C virus antibody prevalence, B
symptoms, poor performance status and CD5 positivity differed significantly
between the primary splenic DLBCL and control DLBCL groups. Primary splenic DLBCL
cases were classified histopathologically into two groups [white pulp pattern (n
= 46), red pulp pattern (n = 20)]. Survival analysis showed no difference in
overall survival between the primary splenic DLBCL and the control group, but the
former had a more favourable progression-free survival. In the examination of
primary splenic DLBCL, the white pulp pattern was statistically associated with a
lower performance status (2-4), and a lower CD5 positivity than the red pulp
pattern. In the survival analysis, the red pulp pattern demonstrated poorer
overall survival. Multivariate analysis of overall survival in primary splenic
DLBCL cases identified CD5 positivity as an indicator of poor prognosis.
Classifying primary splenic DLBCL into white and red pulp patterns was useful in
terms of clinicopathological features and overall survival.
PMID- 28493518
TI - On the relationships between DSM-5 dysfunctional personality traits and social
cognition deficits: A study in a sample of consecutively admitted Italian
psychotherapy patients.
AB - This study aims at testing the hypothesis that the Diagnostic and Statistical
Manual of Mental Disorders fifth edition (DSM-5) alternative model of personality
disorder (AMPD) traits may be significantly associated with deficits on 2
different social cognition tasks, namely, the Reading the Mind in the Eyes Test
and the Movie for the Assessment of Social Cognition, in a sample of
consecutively admitted inpatients and outpatients. The sample was composed of 181
consecutively admitted participants (57.5% women; mean age = 38.58 years).
Correlation coefficients and partial correlation coefficients were computed in
order to assess the associations among social cognition tasks, DSM-5 AMPD traits,
and dimensionally assessed DSM-5 Section II personality disorders. Specific
maladaptive traits listed in the DSM-5 AMPD were significantly associated with
Reading the Mind in the Eyes Test scores and Movie for the Assessment of Social
Cognition scores, even when the effect of selected DSM-5 Section II personality
disorders was controlled for. Our results support the relevance of studying
social cognitive functioning in subjects suffering from personality disorders.
PMID- 28493519
TI - Neurotransmitters behind pain relief with transcranial magnetic stimulation -
positron emission tomography evidence for release of endogenous opioids.
AB - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) at M1/S1 cortex
has been shown to alleviate neuropathic pain. OBJECTIVES: To investigate the
possible neurobiological correlates of cortical neurostimulation for the pain
relief. METHODS: We studied the effects of M1/S1 rTMS on nociception, brain
dopamine D2 and MU-opioid receptors using a randomized, sham-controlled, double
blinded crossover study design and 3D-positron emission tomography (PET). Ten
healthy subjects underwent active and sham rTMS treatments to the right M1/S1
cortex with E-field navigated device. Dopamine D2 and MU-receptor availabilities
were assessed with PET radiotracers [11 C]raclopride and [11 C]carfentanil after
each rTMS treatment. Thermal quantitative sensory testing (QST), contact heat
evoked potential (CHEP) and blink reflex (BR) recordings were performed between
the PET scans. RESULTS: MU-Opioid receptor availability was lower after active
than sham rTMS (P <= 0.0001) suggested release of endogenous opioids in the right
ventral striatum, medial orbitofrontal, prefrontal and anterior cingulate
cortices, and left insula, superior temporal gyrus, dorsolateral prefrontal
cortex and precentral gyrus. There were no differences in striatal dopamine D2
receptor availability between active and sham rTMS, consistent with lack of long
lasting measurable dopamine release. Active rTMS potentiated the dopamine
regulated habituation of the BR compared to sham (P = 0.02). Thermal QST and CHEP
remained unchanged after active rTMS. CONCLUSIONS: rTMS given to M1/S1 activates
the endogenous opioid system in a wide brain network associated with processing
of pain and other salient stimuli. Direct enhancement of top-down opioid-mediated
inhibition may partly explain the clinical analgesic effects of rTMS.
SIGNIFICANCE: Neurobiological correlates of rTMS for the pain relief are unclear.
rTMS on M1/S1 with 11 C-carfentanyl-PET activates endogenous opioids. Thermal and
heat pain thresholds remain unchanged. rTMS induces top-down opioid-mediated
inhibition but not change the sensory discrimination of painful stimuli.
PMID- 28493520
TI - HBV-specific CD4+ cytotoxic T cells in hepatocellular carcinoma are less
cytolytic toward tumor cells and suppress CD8+ T cell-mediated antitumor
immunity.
AB - In East Asia and sub-Saharan Africa, chronic infection is the main cause of the
development of hepatocellular carcinoma, an aggressive cancer with low survival
rate. Cytotoxic T cell-based immunotherapy is a promising treatment strategy.
Here, we investigated the possibility of using HBV-specific CD4+ cytotoxic T
cells to eliminate tumor cells. The naturally occurring HBV-specific cytotoxic
CD4+ and CD8+ T cells were identified by HBV peptide pool stimulation. We found
that in HBV-induced hepatocellular carcinoma patients, the HBV-specific cytotoxic
CD4+ T cells and cytotoxic CD8+ T cells were present at similar numbers. But
compared to the CD8+ cytotoxic T cells, the CD4+ cytotoxic T cells secreted less
cytolytic factors granzyme A (GzmA) and granzyme B (GzmB), and were less
effective at eliminating tumor cells. In addition, despite being able to secrete
cytolytic factors, CD4+ T cells suppressed the cytotoxicity mediated by CD8+ T
cells, even when CD4+ CD25+ regulator T cells were absent. Interestingly, we
found that interleukin 10 (IL-10)-secreting Tr1 cells were enriched in the
cytotoxic CD4+ T cells. Neutralization of IL-10 abrogated the suppression of CD8+
T cells by CD4+ CD25- T cells. Neither the frequency nor the absolute number of
HBV-specific CD4+ cytotoxic T cells were correlated with the clinical outcome of
advanced stage hepatocellular carcinoma patients. Together, this study
demonstrated that in HBV-related hepatocellular carcinoma, CD4+ T cell-mediated
cytotoxicity was present naturally in the host and had the potential to exert
antitumor immunity, but its capacity was limited and was associated with
immunoregulatory properties.
PMID- 28493521
TI - A Freeze-Concentration and Polyampholyte-Modified Liposome-Based Antigen-Delivery
System for Effective Immunotherapy.
AB - Immunotherapy is an exciting new approach to cancer treatment. The development of
a novel freeze-concentration method is described that could be applicable in
immunotherapy. The method involves freezing cells in the presence of pH
sensitive, polyampholyte-modified liposomes with encapsulated ovalbumin (OVA) as
the antigen. In RAW 264.7 cells, compared to unfrozen, freeze-concentration of
polyampholyte-modified liposomes encapsulating OVA resulted in efficient OVA
uptake and also allowed its delivery to the cytosol. Efficient delivery of OVA to
the cytosol was shown to be partly due to the pH-dependence of the polyampholyte
modified liposomes. Cytosolic OVA delivery also resulted in significant up
regulation of the major histocompatibility complex class I pathway through cross
stimulation, as well as an increase in the release of IL-1beta, IL-6, and TNF
alpha. The results demonstrate that the combination of a simple freeze
concentration method and polyampholyte-modified liposomes might be useful in
future immunotherapy applications.
PMID- 28493522
TI - National survey on turnaround time of clinical biochemistry tests in 738
laboratories in China.
AB - BACKGROUND: This survey was initiated to estimate the current status of
turnaround time (TAT) monitoring of clinical biochemistry in China, provide
baseline data for establishment of quality specifications and analyze the impact
factors of TAT. METHODS: 738 laboratories were included. Questionnaires involved
general information and data of related indicators of TAT during 1 week were
provided to participating laboratories. Nine quality indicators were covered,
which were medians, 90th and outlier rates of pre-examination, examination, and
post-examination TAT. The 25th percentile, median, and 75th percentile of TATs
were calculated as optimum, desirable, and minimum quality specifications.
Percentages and sigma values were used to describe the outlier rates. Mann
Whitney and Kruskal-Wallis tests were used to identify the potential impacts of
TAT. RESULTS: Response rate of this survey was 46.44%. More than 50% of the
laboratories indicated they had set up target TATs in three time intervals and
monitored TATs generally. The post-examination TAT of most laboratories was 0min,
while the pre-examination and examination TAT varied. Sigma values of outlier
rates for 45%~60% of laboratories were above 4, while 15%~20% of labs whose sigma
values were below 3. Group comparisons suggested nurse or mechanical pipeline
transportation, link laboratory information system with hospital information
system, and using computer reporting instead of printing report were related to
shorter TATs. CONCLUSIONS: Despite of the remarkable progresses of TATs in China,
there was also room to improve. Laboratories should strengthen the construction
of information systems, identify reasons for TAT delay to improve the service
quality continuously.
PMID- 28493523
TI - Fibrillar collagen genes are not coordinately upregulated with TGF beta1
expression in finasteride-treated prostate.
AB - Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary
tract symptoms (LUTS) in older men. In this regard, recent studies have attempted
to define the relationships between prostatic fibrosis, LUTS, and increased
expression of transforming growth factor beta1 (TGF beta1) in BHP. Therapeutic
approaches for BPH such as 5-alpha-reductase inhibitors and alpha-adrenergic
blocking agents increase TGF beta1 expression in the prostatic tissue. Here, we
investigated the effects of the 5-alpha-reductase inhibitor-finasteride-on rat
ventral prostate tissue, especially with regard to the tissue distribution and
gene expression of fibrillar collagens. Adult Wistar rats (n = 15) were treated
with finasteride (25 mg/kg/day) by subcutaneous injection for 7 and 30 days. Age
matched, vehicle-treated (n = 15) adult Wistar rats were used as control.
Finasteride treatment reduced prostate size and increased the area of types I and
III collagen fibers in the prostatic stroma. As expected, TGF beta1 mRNA
expression was upregulated by finasteride treatment. However, COL1A1 and COL3A1
mRNA expressions decreased after both 7 and 30 days of finasteride treatment,
suggesting that finasteride treatment promotes prostate parenchyma and stroma
changes, which lead to the observed types I and III collagen remodeling without
de novo collagen synthesis. The upregulation of TGF beta1 mRNA and protein
associated with the 5-alpha-reductase inhibitor is more closely related to
epithelial and stromal cell death pathways than to prostatic fibrosis.
PMID- 28493524
TI - Rapid identification and global characterization of multiple constituents from
the essential oil of Cortex Dictamni based on GC-MS.
AB - The root of Dictamnus dasycarpus Turcz., also known as Cortex Dictamni, is a
Chinese herbal medicine that has been commonly used in the treatment of
inflammation, microbial infection, cancer, and other diseases in China for
thousands of years. Recently, the essential oil of Cortex Dictamni has been
widely studied, and a large number of volatile constituents have been discovered.
However, the research of the essential oil of Cortex Dictamni in vivo remains
unknown, especially the constituents absorbed into blood after oral
administration. Hence, a sensitive and rapid method using gas chromatography with
mass spectrometry combined with MassHunter software and the National Institute of
Standards and Technology 2014 database was used to investigate the absorbed
components in rat serum after oral administration of the essential oil of Cortex
Dictamni. With the established method, a total of 36 compounds were screened and
identified in the essential oil of Cortex Dictamni based on the mass spectrometry
data and compound database. Among them, eight compounds, elemol, thymol methyl
ether, beta-eudesmol, beta-cyclocostunolid, guaiazulene, trans-4-hydroxystilbene,
ethyl oleate, and monoelaidin, were tentatively characterized in rat serum. This
work demonstrated that the established method proved to be a powerful technique
for rapid, simple, reliable, and automated identification of bioactive components
of herbal medicine.
PMID- 28493528
TI - What the neighbors say.
PMID- 28493526
TI - Real-time MRI guidance of cardiac interventions.
AB - : Cardiac magnetic resonance imaging (MRI) is appealing to guide complex cardiac
procedures because it is ionizing radiation-free and offers flexible soft-tissue
contrast. Interventional cardiac MR promises to improve existing procedures and
enable new ones for complex arrhythmias, as well as congenital and structural
heart disease. Guiding invasive procedures demands faster image acquisition,
reconstruction and analysis, as well as intuitive intraprocedural display of
imaging data. Standard cardiac MR techniques such as 3D anatomical imaging,
cardiac function and flow, parameter mapping, and late-gadolinium enhancement can
be used to gather valuable clinical data at various procedural stages. Rapid
intraprocedural image analysis can extract and highlight critical information
about interventional targets and outcomes. In some cases, real-time interactive
imaging is used to provide a continuous stream of images displayed to
interventionalists for dynamic device navigation. Alternatively, devices are
navigated relative to a roadmap of major cardiac structures generated through
fast segmentation and registration. Interventional devices can be visualized and
tracked throughout a procedure with specialized imaging methods. In a clinical
setting, advanced imaging must be integrated with other clinical tools and
patient data. In order to perform these complex procedures, interventional
cardiac MR relies on customized equipment, such as interactive imaging
environments, in-room image display, audio communication, hemodynamic monitoring
and recording systems, and electroanatomical mapping and ablation systems.
Operating in this sophisticated environment requires coordination and planning.
This review provides an overview of the imaging technology used in MRI-guided
cardiac interventions. Specifically, this review outlines clinical targets,
standard image acquisition and analysis tools, and the integration of these tools
into clinical workflow. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 5 J. Magn.
Reson. Imaging 2017;46:935-950.
PMID- 28493527
TI - Characterization of a sandwich ELISA for the quantification of all human
periostin isoforms.
AB - BACKGROUND: Periostin (osteoblast-specific factor OSF-2) is a secreted protein
occurring in seven known isoforms, and it is involved in a variety of biological
processes in osteology, tissue repair, oncology, cardiovascular and respiratory
systems or allergic manifestations. To analyze functional aspects of periostin,
or the ability of periostin as potential biomarker in physiological and
pathological conditions, there is the need for a precise, well-characterized
assay that detects periostin in peripheral blood. METHODS: In this study the
development of a sandwich ELISA using monoclonal and affinity-purified polyclonal
anti-human periostin antibodies was described. Antibodies were characterized by
mapping of linear epitopes with microarray technology, and by analyzing cross
reactive binding to human periostin isoforms with western blot. The assay was
validated according to ICH/EMEA guidelines. RESULTS: The monoclonal coating
antibody binds to a linear epitope conserved between the isoforms. The polyclonal
detection antibody recognizes multiple conserved linear epitopes. Therefore, the
periostin ELISA detects all known human periostin isoforms. The assay is
optimized for human serum and plasma and covers a calibration range between 125
and 4000 pmol/L for isoform 1. Assay characteristics, such as precision (intra
assay: <=3%, inter-assay: <=6%), spike-recovery (83%-106%), dilution linearity
(95%-126%), as well as sample stability meet the standards of acceptance.
Periostin levels of apparently healthy individuals are 864+/-269 pmol/L (serum)
and 817+/-170 pmol/L (plasma) respectively. CONCLUSION: This ELISA is a reliable
and accurate tool for determination of all currently known periostin isoforms in
human healthy and diseased samples.
PMID- 28493529
TI - Pain in knee osteoarthritis is associated with variation in the neurokinin
1/substance P receptor (TACR1) gene.
AB - BACKGROUND: Substance P (SP) is a pain- and inflammation-related neuropeptide
which preferentially binds to the neurokinin receptor 1 (NK1 ). SP and NK1
receptors have been implicated in joint pain, inflammation and damage in animal
models and human studies of osteoarthritis (OA). The aim of this study was to
test if genetic variation at the neurokinin 1 receptor gene (TACR1) is associated
with pain in individuals with radiographic knee OA. METHODS: Participants from
the Genetics of OA and Lifestyle study were used for the discovery group (n =
1615). Genotype data for six SNPs selected to cover most variation in the TACR1
gene were used to test for an association with symptomatic OA. Replication
analysis was performed using data from the Chingford 1000 Women Study,
Hertfordshire Cohort Study, Tasmanian Older Adult Cohort Study and the Clearwater
OA Study. In total, n = 1715 symptomatic OA and n = 735 asymptomatic OA
individuals were analysed. RESULTS: Out of six SNPs tested in the TACR1 gene, one
(rs11688000) showed a nominally significant association with a decreased risk of
symptomatic OA in the discovery cohort. This was then replicated in four
additional cohorts. After adjusting for age, gender, body mass index and
radiographic severity, the G (minor) allele at rs11688000 was associated with a
decreased risk of symptomatic OA compared to asymptomatic OA cases (p = 9.90 * 10
4 , OR = 0.79 95% 0.68-0.90 after meta-analysis). CONCLUSIONS: This study
supports a contribution from the TACR1 gene in human OA pain, supporting further
investigation of this gene's function in OA. SIGNIFICANCE: This study contributes
to the knowledge of the genetics of painful osteoarthritis, a condition which
affects millions of individuals worldwide. Specifically, a contribution from the
TACR1 gene to modulating pain sensitivity in osteoarthritis is suggested.
PMID- 28493530
TI - M2 macrophages induce EMT through the TGF-beta/Smad2 signaling pathway.
AB - IPF is characterized by fibroblast accumulation, collagen deposition, and ECM
remodeling, with myofibroblasts believed to be the effector cell type.
Myofibroblasts develop due to EMT of lung alveolar epithelial cells, which can be
induced by TGF-beta. M2 macrophages, a macrophage subpopulation, secrete large
amounts of TGF-beta. To clarify the relationship between IPF, EMT, TGF-beta, and
M2 macrophages, a bleomycin-induced pulmonary fibrosis mouse model was used.
Seventeen days after mice were treated with bleomycin, the successful
establishment of a pulmonary fibrosis model was confirmed by HE stain and
Masson's trichrome stain. We found evidence in support of EMT, such as elevated
protein levels of alpha-SMA in lung tissue and decreased levels of E-cadherin and
CK-18. Additionally, increased TGF-beta levels and TGF-beta/Smad2 signaling
activation was observed. Macrophages were recruited to pulmonary alveoli.
Alveolar macrophages were phenotyped and identified as M2 macrophages, with up
regulated CD206 on the cell surfaces. For in vitro studies, we treated RAW 264.7
cells with IL-4 for 24 h, and the cells were then utilized as M2 macrophages. TGF
beta levels increased significantly in the culture supernatant. Forty-eight hours
after lung epithelial cells (MLE-12) were co-cultured with the M2 macrophages,
the expression of alpha-SMA increased, and E-cadherin and CK-18 decreased. When a
TGF-beta receptor inhibitor, LY2109761 was used, the EMT induced by M2
macrophages was blocked. In conclusion, we demonstrated that M2 macrophages
induce EMT through the TGF-beta/Smad2 signaling pathway.
PMID- 28493532
TI - Metrics and the Scientific Literature: Deciding What to Read.
PMID- 28493533
TI - Combination diagnosis of multi-slice spiral computed tomography and secretary
phospholipase A2-IIa for solitary pulmonary nodules.
AB - INTRODUCTION: This study was aimed to compare the diagnostic value of multi-slice
spiral computed tomography (CT) and secretary phospholipase A2-IIa (sPLA2-IIa) in
differentiating between malignant and benign solitary pulmonary nodules (SPNs).
METHODS: A total of 223 patients with SPNs (91 patients with malignant SPNs and
132 patients with benign SPNs) were included from Weihai Central Hospital during
October 2014 to December 2016. SPN diagnosis was confirmed in all patients using
needle biopsy, surgery and bronchoscopy. The patients were managed with dynamic
multi-slice CT scans, and their sPLA2-IIa levels were also detected. By selecting
the area of interest of focus, the perfusion parameters of multi-slice CT
targeting the focus were obtained. RESULTS: The levels of MTT, PS, BV, BF and
sPLA2-IIa significantly increased with increasing severity of SPNs (P<.05).
Notably, BV (area under the ROC curve [AUC]=0.915; 95%CI: 0.88-0.95;
sensitivity=91.21%; specificity=78.79%) showed a higher potential to discriminate
patients with malignant SPNs from those with benign SPNs than did BF (AUC=0.712;
95%CI: 0.65-0.78; sensitivity=72.50%; specificity=59.10%), PS (AUC=0.772; 95%CI:
0.71-0.84; sensitivity=65.93%; specificity=82.58%) and MTT (AUC=0.600; 95%CI:
0.52-0.68; sensitivity=52.75%; specificity=78.03%). Finally, the combined
diagnostic value of BV and sPLA2-IIa was quite ideal (AUC=0.947; 95%CI: 0.92
0.97; sensitivity=85.70%; specificity=92.70%) for malignant and benign SPNs.
CONCLUSIONS: The combined diagnostic value of BV and sPLA2-IIa appeared as a
desirable detection method for malignant and benign SPNs.
PMID- 28493531
TI - Ternary complex of human RORgamma ligand-binding domain, inverse agonist and SMRT
peptide shows a unique mechanism of corepressor recruitment.
AB - Retinoid-related orphan receptor gamma (RORgamma) directly controls the
differentiation of Th17 cell and the production of interleukin-17, which plays an
integral role in autoimmune diseases. To obtain insight into RORgamma, we have
determined the first crystal structure of a ternary complex containing RORgamma
ligand-binding domain (LBD) bound with a novel synthetic inhibitor and a
repressor peptide, 22-mer peptide from silencing mediator of retinoic acid and
thyroid hormone receptor (SMRT). Comparison of a binary complex of nonliganded
(apo) RORgamma-LBD with a nuclear receptor co-activator (NCoA-1) peptide has
shown that our inhibitor displays a unique mechanism different from those caused
by natural inhibitor, ursolic acid (UA). The compound unprecedentedly induces
indirect disruption of a hydrogen bond between His479 on helix 11 (H11) and
Tyr502 on H12, which is crucial for active conformation. This crystallographic
study will allow us to develop novel synthetic compounds for autoimmune disease
therapy.
PMID- 28493534
TI - Determination of triazine herbicides in juice samples by microwave-assisted ionic
liquid/ionic liquid dispersive liquid-liquid microextraction coupled with high
performance liquid chromatography.
AB - A novel microextraction method, termed microwave-assisted ionic liquid/ionic
liquid dispersive liquid-liquid microextraction, has been developed for the rapid
enrichment and analysis of triazine herbicides in fruit juice samples by high
performance liquid chromatography. Instead of using hazardous organic solvents,
two kinds of ionic liquids, a hydrophobic ionic liquid (1-hexyl-3
methylimidazolium hexafluorophosphate) and a hydrophilic ionic liquid (1-butyl-3
methylimidazolium tetrafluoroborate), were used as the extraction solvent and
dispersion agent, respectively, in this method. The extraction procedure was
induced by the formation of cloudy solution, which was composed of fine drops of
1-hexyl-3-methylimidazolium hexafluorophosphate dispersed entirely into sample
solution with the help of 1-butyl-3-methylimidazolium tetrafluoroborate. In
addition, an ion-pairing agent (NH4 PF6 ) was introduced to improve recoveries of
the ionic liquid phase. Several experimental parameters that might affect the
extraction efficiency were investigated. Under the optimum experimental
conditions, the linearity for determining the analytes was in the range of 5.00
250.00 MUg/L, with the correlation coefficients of 0.9982-0.9997. The practical
application of this effective and green method is demonstrated by the successful
analysis of triazine herbicides in four juice samples, with satisfactory
recoveries (76.7-105.7%) and relative standard deviations (lower than 6.6%). In
general, this method is fast, effective, and robust to determine triazine
herbicides in juice samples.
PMID- 28493535
TI - The mongolian gerbil (Meriones unguiculatus) as a model for inflammation-promoted
prostate carcinogenesis.
AB - One of the recognized issues in prostate cancer research is the lack of animal
models allowing the research of pathological, biochemical, and genetic factors in
immunocompetent animals. Our research group has successfully employed the gerbil
in several studies for prostate diseases. In the present work, we aimed to
analyze the effect of chronic bacterial inflammation on N-methyl-N-nitrosourea
(MNU)-induced prostate carcinogenesis in gerbils. Histopathological assessment of
the prostatic complex revealed that treatment combinations with MNU plus
testosterone or bacterial infection resulted in a promotion of prostate cancer,
with bacterial inflammation being more effective in increasing premalignant and
malignant tissular alterations than testosterone in the prostate. Furthermore,
chronic bacterial inflammation itself induced premalignant lesions in the ventral
lobe and increased their frequency in the dorsolateral lobe as well as malignant
lesions in the ventral prostate. These animals showed a rich inflammatory
microenvironment, characterized as intraluminal and periductal foci. These data
indicate that chronic inflammation induced by Escherichia coli acts as a potent
tumor promoter, in the early stages of carcinogenesis in the gerbil, in line with
the hypothesis of inflammation supporting several steps of tumor development in
the prostate gland.
PMID- 28493537
TI - Exploring the expression bar code of SAA variants for gastric cancer detection.
AB - We reported an integrated platform to explore serum protein variant pattern in
cancer and its utility as a new class of biomarker panel for diagnosis. On the
model study of serum amyloid A (SAA), we employed nanoprobe-based affinity mass
spectrometry for enrichment, identification and quantitation of SAA variants from
serum of 105 gastric cancer patients in comparison with 54 gastritis patients, 54
controls, and 120 patients from other cancer. The result revealed surprisingly
heterogeneous and most comprehensive SAA bar code to date, which comprises 24 SAA
variants including SAA1- and SAA2-encoded products, polymorphic isoforms, N
terminal-truncated forms, and three novel SAA oxidized isotypes, in which the
variant-specific peptide sequence were also confirmed by LC-MS/MS. A diagnostic
model was developed for dimension reduction and computational classification of
the 24 SAA-variant bar code, providing good discrimination (AUC = 0.85 +/- 3.2E
3) for differentiating gastric cancer group from gastritis and normal groups
(sensitivity, 0.76; specificity, 0.81) and was validated with external validation
cohort (sensitivity, 0.71; specificity, 0.74). Our platform not only shed light
on the occurrence and modification extent of under-represented serum protein
variants in cancer, but also suggested a new concept of diagnostic platform by
serum protein variant profile.
PMID- 28493536
TI - Functional hypergraph uncovers novel covariant structures over neurodevelopment.
AB - Brain development during adolescence is marked by substantial changes in brain
structure and function, leading to a stable network topology in adulthood.
However, most prior work has examined the data through the lens of brain areas
connected to one another in large-scale functional networks. Here, we apply a
recently developed hypergraph approach that treats network connections (edges)
rather than brain regions as the unit of interest, allowing us to describe
functional network topology from a fundamentally different perspective.
Capitalizing on a sample of 780 youth imaged as part of the Philadelphia
Neurodevelopmental Cohort, this hypergraph representation of resting-state
functional MRI data reveals three distinct classes of subnetworks (hyperedges):
clusters, bridges, and stars, which respectively represent homogeneously
connected, bipartite, and focal architectures. Cluster hyperedges show a strong
resemblance to previously-described functional modules of the brain including
somatomotor, visual, default mode, and salience systems. In contrast, star
hyperedges represent highly localized subnetworks centered on a small set of
regions, and are distributed across the entire cortex. Finally, bridge hyperedges
link clusters and stars in a core-periphery organization. Notably, developmental
changes within hyperedges are ordered in a similar core-periphery fashion, with
the greatest developmental effects occurring in networked hyperedges within the
functional core. Taken together, these results reveal a novel decomposition of
the network organization of human brain, and further provide a new perspective on
the role of local structures that emerge across neurodevelopment. Hum Brain Mapp
38:3823-3835, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28493538
TI - Fine-scale analysis of heavily invaded Italian freshwater fish assemblages.
AB - Inland waters are highly vulnerable to the introduction and spread of non-native
species, due to heavy human use of aquatic ecosystems and the natural linkages
among streams and lakes. This is particularly noticeable in freshwater fish
communities. To better evaluate how these communities are affected by non-native
species introductions, we conducted a fine-scale analysis of the changes in
Italian freshwater fish assemblages after species introduction. For this
analysis, we collected information on fish species present in 44 basins. The
present Italian freshwater fish fauna is composed of 48 native and 41 established
introduced species, while a further 15 introduced species have been reported but
are not yet considered naturalized. The changes in the fish assemblages mostly
took place in the past 2 centuries and have increased recently, with nearly 60%
of the species introduced in the past 3 decades. The number of species introduced
per basin ranged from 0 to 35 (mean 10.85 +/- 7.77 species/basin), and in 10
basins the number of species introduced is now equal to or even higher than the
number of native species. In the past, introduced species mainly originated from
America, but over the past three decades, an increase of introductions from other
parts of Europe and Asia has been recorded. Our results show that basins already
rich in native species tend to become even richer as a consequence of the
establishment of introduced species. This confirms the trend toward a biotic
homogenization of ecosystems even at a local scale, due to an increase in the
human-mediated spread of generalist species.
PMID- 28493539
TI - The influence of bacteria on multitrophic interactions among plants, psyllids,
and pathogen.
AB - The recent emergence of several plant diseases caused by psyllid-borne bacterial
pathogens worldwide (Candidatus Liberibacter spp.) has created renewed interest
on the interaction between psyllids and bacteria. In spite of these efforts to
understand psyllid association with bacteria, many aspects of their interactions
remain poorly understood. As more organisms are studied, subtleties on the
molecular interactions as well as on the effects of the bacteria on the psyllid
host are being uncovered. Additionally, psyllid-borne bacterial phytopathogens
can also affect the host plant, which in turn can impact psyllid physiology and
behavior. Here, we review the current literature on different aspects of the
influence of bacteria on multitrophic interactions among plants, psyllids, and
pathogens. We then highlight gaps that need to be addressed to advance this
field, which can have significant implications for controlling these newly
emergent and other plant diseases.
PMID- 28493540
TI - Corrigendum: A GAL4-inducible transgenic tool kit for the in vivo modulation of
Rho GTPase activity in zebrafish.
PMID- 28493541
TI - Sudden gains in exposure-focused cognitive-behavioral group therapy for panic
disorder.
AB - : In the context of psychological treatment, a sudden gain is a large and
enduring improvement in symptom severity that occurs between two single therapy
sessions. The influence of sudden gains on long-term outcomes and functional
impairment in anxiety disorders is not well understood, and little is known with
regard to panic disorder in particular. In addition, previous research on
patients with anxiety disorders has produced inconsistent results regarding the
relationship between sudden gains and cognitive change. We examined the incidence
of sudden gains in a large sample (n = 116) of panic disorder patients undergoing
exposure-focused cognitive-behavioral group therapy, and compared panic severity,
functional impairment, and cognitive change in patients with and without sudden
gains at posttreatment and 6-month follow-up. Participants who experienced sudden
gains displayed lower levels of panic severity and functional impairment at
posttreatment and 6-month follow-up than those who did not experience sudden
gains. However, we observed no difference in cognitive changes between groups,
either at posttreatment or at follow-up. Our results demonstrate that the
beneficial effects of sudden gains on therapeutic outcomes not only extend to
long-term and functional outcome measures but are also evident in less cognitive
(i.e., exposure-focused) forms of psychological treatment. KEY PRACTITIONER
MESSAGE: Sudden gains are common in panic disorder patients undergoing exposure
based cognitive-behavioral group therapy. Sudden gains during exposure-focused
therapy are linked to greater improvement in panic disorder severity and
functional impairment. The positive impact of sudden gains on panic disorder
severity and functional impairment is maintained in the long term.
PMID- 28493542
TI - Dynamic changes of metabolite accumulation in Scrophulariae Radix based on liquid
chromatography-tandem mass spectrometry combined with multivariate statistical
analysis.
AB - Scrophulariae Radix is one of the most popular traditional Chinese medicines. The
harvesting time of Scrophulariae Radix is closely related to the quality of
products in this traditional Chinese medicine. The goal of the study is to
analyze the dynamic changes of metabolite accumulation in Scrophulariae Radix.
The difference of constituents in Scrophulariae Radix harvested at different
times was analyzed by liquid chromatography with triple quadrupole-time of flight
tandem mass spectrometry coupled with principal component analysis and partial
least-square discriminant analysis. According to the accurate mass of molecular
and product ions provided by triple quadrupole-time of flight tandem mass
spectrometry, a total of 30 differential constituents were identified.
Furthermore, the contents of ten index differential constituents in Scrophulariae
Radix were simultaneously determined by liquid chromatography coupled with triple
quadrupole-linear ion trap tandem mass spectrometry. Gray relational analysis was
performed to evaluate the samples harvested at different times according to the
contents of ten constituents. All of the results demonstrated that the quality of
Scrophulariae Radix collected at traditional harvest time was better. This study
will provide the basic information for revealing the dynamic change law of
metabolite accumulation of Scrophulariae Radix and exploring its quality forming
mechanism.
PMID- 28493543
TI - Contribution of patient, physician, and environmental factors to demographic and
health variation in colonoscopy follow-up for abnormal colorectal cancer
screening test results.
AB - BACKGROUND: Patient, physician, and environmental factors were identified, and
the authors examined the contribution of these factors to demographic and health
variation in colonoscopy follow-up after a positive fecal occult blood test/fecal
immunochemical test (FOBT/FIT) screening. METHODS: In total, 76,243 FOBT/FIT
positive patients were identified from 120 Veterans Health Administration (VHA)
facilities between August 16, 2009 and March 20, 2011 and were followed for 6
months. Patient demographic (race/ethnicity, sex, age, marital status) and health
characteristics (comorbidities), physician characteristics (training level,
whether primary care provider) and behaviors (inappropriate FOBT/FIT screening),
and environmental factors (geographic access, facility type) were identified from
VHA administrative records. Patient behaviors (refusal, private sector
colonoscopy use) were estimated with statistical text mining conducted on clinic
notes, and follow-up predictors and adjusted rates were estimated using
hierarchical logistic regression. RESULTS: Roughly 50% of individuals completed a
colonoscopy at a VHA facility within 6 months. Age and comorbidity score were
negatively associated with follow-up. Blacks were more likely to receive follow
up than whites. Environmental factors attenuated but did not fully account for
these differences. Patient behaviors (refusal, private sector colonoscopy use)
and physician behaviors (inappropriate screening) fully accounted for the small
reverse race disparity and attenuated variation by age and comorbidity score.
Patient behaviors (refusal and private sector colonoscopy use) contributed more
to variation in follow-up rates than physician behaviors (inappropriate
screening). CONCLUSIONS: In the VHA, blacks are more likely to receive
colonoscopy follow-up for positive FOBT/FIT results than whites, and follow-up
rates markedly decline with advancing age and comorbidity burden. Patient and
physician behaviors explain race variation in follow-up rates and contribute to
variation by age and comorbidity burden. Cancer 2017;123:3502-12. Published 2017.
This article is a US Government work and is in the public domain in the USA.
PMID- 28493544
TI - Recurrence patterns following irreversible electroporation for hepatic
malignancies.
AB - BACKGROUND: Irreversible electroporation (IRE) has emerged as a novel, safe
ablative therapy for peri-vascular lesions. However, there remains a paucity of
data on long-term outcomes. METHODS: We identified patients who underwent open
IRE (1/2011-6/2015) for primary and secondary hepatic malignancies. Local
ablation-zone recurrence (LR) was determined by cross-sectional imaging.
Cumulative incidence (CumI) of LR was calculated and a competing risks regression
assessed factors associated with LR. RESULTS: Forty patients had 77 lesions
treated. The majority of lesions were of colorectal origin (74%). Median tumor
size was 1.3 cm (range 0.5-6). Most patients (86%) had prior systemic therapy and
29% received systemic therapy following IRE. With a median follow-up of 25.7
months (range 4.5-58.8 months), 10 lesions in 9 patients recurred locally (CumI:
13.4%, 95%CI: 7.8-22.2%). Median estimated time to LR was not reached and no LR
occurred after 19 months. Factors significantly associated with LR included
ablation zone size (HR 1.58; 95%CI 1.12-2.23; P = 0.0093) and body mass index (HR
1.21 95%CI 1.10-1.34; P = 0.0001). CONCLUSION: IRE LR rates were low after the
treatment of well selected, small tumors. This technique is useful for lesions in
anatomic locations precluding resection or thermal ablation.
PMID- 28493548
TI - Time for a New Approach to Studying Older People with Ischemic Heart Disease.
PMID- 28493546
TI - Palmar-plantar erythrodysesthesia syndrome following treatment with high-dose
methotrexate or high-dose cytarabine.
AB - BACKGROUND: Palmar-plantar erythrodysesthesia syndrome (PPES) is an uncommon side
effect of high-dose cytarabine or methotrexate. Prior case reports of PPES have
been limited, and the predisposing factors for the development of PPES remain
unknown. METHODS: A review of databases identified 22 patients (1.3%) who
developed 39 episodes of PPES among 1720 patients after treatment with high-dose
cytarabine or methotrexate. RESULTS: Symptoms lasted a mean of 6.4 days. Hands
and feet were both involved in 68% of the initial episodes. Parenteral opioids
were required for pain control by 27% of the patients. In comparison with the
1698 children treated with similar therapy, the children who developed PPES were
older (mean age at diagnosis, 14.3 vs 7.7 years; P = 7.5 * 10-7 ). The frequency
of PPES was less common in patients receiving methotrexate alone (7 of 946 or
0.7%) versus cytarabine (7 of 205 or 3.4%; P = .005) but was not different for
those receiving both high-dose methotrexate and cytarabine (8 of 569 or 1.4%; P =
.32). Prolonged infusions of methotrexate were associated with less frequent PPES
in comparison with rapid infusions (P = 1.5 * 10-5 ), as was the co
administration of dexamethasone with cytarabine (P = 2.5 * 10-6 ). Self-described
race and sex were not associated with PPES. In a multivariate analysis, older age
and high-dose cytarabine administration without dexamethasone remained associated
with PPES (P = 1.1 * 10-4 and P = .038, respectively). A genome-wide association
study did not identify any associations with PPES meeting the genome-wide
significance threshold, but top variants were enriched for skin expression
quantitative trait loci, including rs11764092 in AUTS2 (P = 6.45 * 10-5 ).
CONCLUSIONS: These data provide new insight into the incidence of PPES as well as
its risk factors. Cancer 2017;123:3602-8. (c) 2017 American Cancer Society.
PMID- 28493547
TI - Clinical trial enrollment of adolescents and young adults with sarcoma.
AB - More than half of all sarcomas occur in adolescents and young adults (AYAs) aged
15 to 39 years. After the publication of the AYA series in the April 1, 2016
issue of Cancer, several leaders in the field of sarcoma across disciplines
gathered to discuss the status of sarcoma clinical research in AYAs. They
determined that a focused effort to include the underrepresented and understudied
AYA population in current and future sarcoma clinical trials is overdue. Trial
enrichment for AYA-aged sarcoma patients will produce more meaningful results
that better represent the disease's biology, epidemiology, and treatment
environment. To address the current deficit, this commentary outlines changes
believed to be necessary to expediently achieve an increase in the enrollment of
AYAs in sarcoma clinical trials. Cancer 2017;123:3434-40. (c) 2017 American
Cancer Society.
PMID- 28493549
TI - Transcription factor RBP-J-mediated signalling regulates basophil
immunoregulatory function in mouse asthma model.
AB - Basophils (BA) play an important role in the promotion of aberrant T helper type
2 (Th2) immune responses in asthma. It is not only the effective cell, but also
modulates the initiation of Th2 immune responses. We earlier demonstrated that
Notch signalling regulates the biological function of BAin vitro. However,
whether this pathway plays the same role in vivo is not clear. The purpose of the
present study was to investigate the effect of Notch signalling on BA function in
the regulation of allergic airway inflammation in a murine model of asthma. Bone
marrow BA were prepared by bone marrow cell culture in the presence of
recombinant interleukin-3 (rIL-3; 300 pg/ml) for 7 days, followed by isolation of
the CD49b+ microbeads. The recombination signal binding protein J (RBP-J-/- ) BA
were co-cultured with T cells, and the supernatant and the T-cell subtypes were
examined. The results indicated disruption of the capacity of BA for antigen
presentation alongside an up-regulation of the immunoregulatory function. This
was possibly due to the low expression of OX40L in the RBP-J-/- BA. Basophils
were adoptively transferred to ovalbumin-sensitized recipient mice, to establish
an asthma model. Lung pathology, cytokine profiles of brobchoalveolar fluid,
airway hyperactivity and the absolute number of Th1/Th2 cells in lungs were
determined. Overall, our results indicate that the RBP-J-mediated Notch
signalling is critical for BA-dependent immunoregulation. Deficiency of RBP-J
influences the immunoregulatory functions of BA, which include activation of T
cells and their differentiation into T helper cell subtypes. The Notch signalling
pathway is a potential therapeutic target for BA-based immunotherapy against
asthma.
PMID- 28493550
TI - Emotion Reactivity, Comfort Expressing Emotions, and Future Suicidal Ideation in
Emerging Adults.
AB - OBJECTIVE: Emotion reactivity and difficulties in expressing emotions have been
implicated in risk for suicidal behavior. This study examined comfort in
expressing emotions (positive vs. negative) and depressive symptoms as mediators
of the prospective relation between emotion reactivity and suicidal ideation.
DESIGN: Emerging adults (N = 143; 72% female; 28% White) completed measures of
emotion reactivity, comfort expressing emotions, and suicidal ideation at
baseline and of depressive symptoms and suicidal ideation 12 months later.
RESULTS: Emotion reactivity predicted suicidal ideation at follow-up through
depressive symptoms. Difficulty expressing love-but not happiness, sadness, and
anger-partially mediated the relationship between emotion reactivity and suicidal
ideation at follow-up before but not after adjusting for baseline ideation.
CONCLUSION: The relation between high emotion reactivity and suicidal ideation
may be explained by discomfort in the expression of positive emotions and by
depressive symptoms. Promotion of comfort in positive emotion expression may
reduce vulnerability to suicidal ideation.
PMID- 28493552
TI - Multigene assays: Implications for breast cancer staging.
PMID- 28493551
TI - Utilization of a Sobering Center for Acute Alcohol Intoxication.
AB - OBJECTIVE: The objective was to describe the population utilizing a sobering
center for public alcohol intoxication and compare between single-visit users,
repeat users, and high users. METHODS: We conducted a secondary analysis of 1,271
adults cared for in a sobering center from July 2014 to June 2015. We divided the
population into three groups-single use (one visit), repeat users (two to five
visits), and high (six or more) users-and evaluated demographics, lifetime health
diagnoses utilizing the Elixhauser Comorbidity Index, rates of public service
utilization including ambulance and emergency department, and related costs.
RESULTS: The population was primarily male, middle-aged, and ethnically diverse.
Compared to single-visit users (n = 869), repeat (n = 287) and high users (n =
115) were older, were more likely to be currently homeless, and had spent more
time homeless. Repeat and high users had significantly higher rates of
hypertension, liver disease, diabetes, depression, psychoses, and drug abuse
diagnoses compared to single-visit users. In addition to sobering visits,
utilization of ambulance and ED and related costs were significantly greater for
the high users compared to repeat and single-visit users. CONCLUSIONS: From an
overall heterogeneous population, more frequent utilizers of the sobering center,
both high and repeat users compared to low users, had significantly greater
prevalence of chronic disorders, service utilization, and homelessness. Findings
indicate that a sobering center can have a prominent role in the care for those
with acute alcohol intoxication, particularly those individuals with chronic
public intoxication who are likewise homeless. Further longitudinal research
could offer important insights as to the population served over time,
investigating changes in utilization and efforts toward health and housing
stabilization.
PMID- 28493553
TI - Regulation of cytokinesis during corticogenesis: focus on the midbody.
AB - Development of the cerebral cortices depends on tight regulation of cell
divisions. In this system, stem and progenitor cells undergo symmetric and
asymmetric divisions to ultimately produce neurons that establish the layers of
the cortex. Cell division culminates with the formation of the midbody, a
transient organelle that establishes the site of abscission between nascent
daughter cells. During cytokinetic abscission, the final stage of cell division,
one daughter cell will inherit the midbody remnant, which can then maintain or
expel the remnant, but mechanisms and circumstances influencing this decision are
unclear. This review describes the midbody and its constituent proteins, as well
as the known consequences of their manipulation during cortical development. The
potential functional relevance of midbody mechanisms is discussed.
PMID- 28493555
TI - Parental Secondary Stress: The Often Hidden Consequences of Nonsuicidal Self
Injury in Youth.
AB - OBJECTIVE: This study aims to deepen understanding of the effects on parents of
having a self-injuring child by (a) analyzing differences in dimensions of
caregiver strain between caregivers of youth with nonsuicidal self-injury (NSSI+)
and parents of youth with no known mental health history (MH-); (b) identifying
factors that contribute to caregiver strain; and (c) examining parent outcome
expectancies. METHOD: Participants were 196 NSSI+ parents and 57 MH- parents.
Quantitative measures of psychosocial variables, parent mental health and support
variables, and child self-injury characteristics were assessed in relation to
caregiver strain, and NSSI+ parental expectancies were assessed via mixed
methods. RESULTS: Parents with a NSSI+ youth were more likely to exhibit all
forms of objective and subjective strain than parents of youth with no mental
health challenges. Despite this, many parents expressed beliefs that their child
would experience personal growth as a result of their NSSI experience.
CONCLUSION: Findings reveal the important role of mindful parenting practices and
informal social support.
PMID- 28493556
TI - Association of Anticipated and Laboratory-Derived Alcohol Stimulation, Sedation,
and Reward.
AB - BACKGROUND: Laboratory alcohol challenges are the "gold standard" for obtaining
accurate measurements of subjective alcohol stimulation, sedation, and reward.
However, these approaches are time and resource intensive. This study examined
the extent to which self-reported anticipated alcohol stimulation, sedation, and
reward corresponded with those same responses measured with the Biphasic Alcohol
Effects Scale (BAES), Brief-BAES (B-BAES), and Drug Effects Questionnaire (DEQ)
during a controlled laboratory alcohol challenge. METHODS: Participants were 106
light-to-heavy social drinkers (58.5% male; mean +/- SD age = 35.8 +/- 3.2 years)
who completed the Anticipated BAES and DEQ, as well as laboratory-derived
versions of these scales 30 and 60 minutes after consuming placebo and 0.8 g/kg
alcohol on separate days as part of laboratory sessions in the Chicago Social
Drinking Project. RESULTS: Anticipated BAES/B-BAES and Anticipated DEQ alcohol
effects were strong predictors of their corresponding laboratory-derived
responses during both the rising limb and at peak breath alcohol concentrations.
Effects were significant even when accounting for age, sex, past-month heavy
drinking frequency, and laboratory session order (placebo or alcohol first).
CONCLUSIONS: This study provides strong preliminary support for measuring
anticipated alcohol effects with the Anticipated BAES/B-BAES and Anticipated DEQ
as a proxy of subjective responses experienced during a controlled laboratory
alcohol challenge. The findings lend support for these measures as viable
alternatives to other anticipatory scales when laboratory-derived alcohol
response measurement is not feasible.
PMID- 28493557
TI - Couples Coping Through Deployment: Findings From a Sample of National Guard
Families.
AB - OBJECTIVE: Military families face numerous changes and stresses as they negotiate
deployments and other life transitions. How they cope with these events is an
important part of their overall well-being and resilience. This longitudinal
study on coping in a sample of National Guard couples examined the association
between the predeployment coping (active vs. avoidant) of each in the
relationship, and their own and their significant others' mental health (anxiety,
depression, posttraumatic stress disorder [PTSD]) and family well-being (dyadic
adjustment and parenting stress) postdeployment. METHOD: A total of 238 matched
couples completed the predeployment survey, 143 matched couples completed the
post, with 122 matched couples completing both pre- and postdeployment surveys.
RESULTS: While active coping was not significantly associated with any outcomes,
predeployment avoidant coping in both soldiers and significant others was
associated with increased anxiety, PTSD, and depression post deployment (actor
effects). Additionally, soldier avoidant coping predeployment was associated with
increased parenting stress for soldiers, while significant other avoidant coping
predeployment was associated with increased relationship distress for significant
others (actor effects). Finally, significant other avoidant coping predeployment
was associated with higher parenting distress for soldiers postdeployment
(partner effect). CONCLUSION: Findings suggest that interventions are needed to
combat avoidant coping (behavioral disengagement, denial, substance abuse)
predeployment because this way of coping is strongly related to negative
outcomes. In addition, those who work clinically with these families should work
to reduce avoidant coping strategies and any familial dynamics exacerbated by
this way of coping.
PMID- 28493558
TI - Comparison of risk of malignancy in a subgroup with atypia of undetermined
significance/follicular lesion of undetermined significance: A meta-analysis.
AB - BACKGROUND: As heterogeneous findings are included in the atypia of undetermined
significance (AUS)/follicular lesion of undetermined significance (FLUS)
category, differing risks of malignancy in subgroups have been reported in
several articles. METHODS: We performed a meta-analysis of full-text publications
written in English found in the Embase and PubMed databases. RESULTS: The 4
tiered subgroup proportion meta-analysis showed that the 95% confidence interval
(95% CI) of the risk of malignancy in the cellular atypia group did not overlap
with the other 3 subgroups and demonstrated a significant difference. Two-tiered
analysis using the cytologic and architectural atypia groups showed that
cytologic atypia group had a 2.64-fold increase in the risk of malignancy
compared with the architectural atypia group. CONCLUSION: The cytologic atypia
had a significantly higher risk of malignancy than the architectural atypia
group, and it should be considered as a separate category.
PMID- 28493561
TI - Distress, omnipotence, and responsibility beliefs in command hallucinations.
AB - OBJECTIVES: Command hallucinations are considered to be one of the most
distressing and disturbing symptoms of schizophrenia. Building on earlier
studies, we compare key attributes in the symptomatic, affective, and cognitive
profiles of people diagnosed with schizophrenia and hearing voices that do (n =
77) or do not (n = 74) give commands. METHODS: The study employed a cross
sectional design, in which we assessed voice severity, distress and control
(PSYRATs), anxiety and depression (HADS), beliefs about voices (BAVQ-R), and
responsibility beliefs (RIQ). Clinical and demographic variables were also
collected. RESULTS: Command hallucinations were found to be more distressing and
controlling, perceived as more omnipotent and malevolent, linked to higher
anxiety and depression, and resisted more than hallucinations without commands.
Commanding voices were also associated with higher conviction ratings for being
personally responsible for preventing harm. CONCLUSIONS: The findings suggest key
differences in the affective and cognitive profiles of people who hear commanding
voices, which have important implications for theory and psychological
interventions. PRACTITIONER POINTS: Command hallucinations are associated with
higher distress, malevolence, and omnipotence. Command hallucinations are
associated with higher responsibility beliefs for preventing harm. Responsibility
beliefs are associated with voice-related distress. Future psychological
interventions for command hallucinations might benefit from focussing not only on
omnipotence, but also on responsibility beliefs, as is done in psychological
therapies for obsessive compulsive disorder. Limitations The cross-sectional
design does not assess issues of causality. We did not measure the presence or
severity of delusions.
PMID- 28493562
TI - Perioperative practices in thyroid surgery: An international survey.
AB - BACKGROUND: Perioperative practices in thyroid surgery vary from one specialty,
institution, or country to the next. We evaluated the preoperative,
intraoperative, and postoperative practices of thyroid surgeons focusing on
preoperative ultrasound, vocal cord evaluation, wound drains, and hospitalization
duration, among others. METHODS: A survey was sent to 7 different otolaryngology
and endocrine/general surgery associations. RESULTS: There were 965 respondents
from 52 countries. Surgeon-performed ultrasound is practiced by more than one
third of respondents. Otolaryngologists perform preoperative and postoperative
vocal cord evaluation more often than endocrine/general surgeons (p < .001).
Sixty percent of respondents either never place drains or place drains <50% of
the time in thyroid lobectomies (43% for total thyroidectomies). Outpatient
thyroid surgery is most frequently performed by surgeons in the United States
(63%). CONCLUSION: This epidemiologic study is the first global thyroid survey of
its kind and clearly demonstrates the variability and evolving trends in thyroid
surgery. (c) 2017 Wiley Periodicals, Inc. Head Neck 39: 1296-1305, 2017.
PMID- 28493559
TI - mTOR referees memory and disease through mRNA repression and competition.
AB - Mammalian target of rapamycin (mTOR) activity is required for memory and is
dysregulated in disease. Activation of mTOR promotes protein synthesis; however,
new studies are demonstrating that mTOR activity also represses the translation
of mRNAs. Almost three decades ago, Kandel and colleagues hypothesised that
memory was due to the induction of positive regulators and removal of negative
constraints. Are these negative constraints repressed mRNAs that code for
proteins that block memory formation? Herein, we will discuss the mRNAs coded by
putative memory suppressors, how activation/inactivation of mTOR repress protein
expression at the synapse, how mTOR activity regulates RNA binding proteins, mRNA
stability, and translation, and what the possible implications of mRNA repression
are to memory and neurodegenerative disorders.
PMID- 28493563
TI - Nalmefene Prevents Alcohol-Induced Neuroinflammation and Alcohol Drinking
Preference in Adolescent Female Mice: Role of TLR4.
AB - BACKGROUND: We previously showed that, by activating innate immune receptors Toll
like 4 (TLR4), adolescent intermittent ethanol (EtOH) exposure causes
neuroinflammation, myelin damage, and behavioral dysfunctions. Recent findings
reveal that clinically used opioid antagonists naltrexone (NT) and naloxone (NX)
inhibit opioid-induced TLR4 signaling and that NT, NX, and nalmefene (NF), the 6
methylene derivative of NX, are able to reduce alcohol drinking escalation.
METHODS: NF (0.1 mg/kg, intraperitoneally) was injected 1 hour prior to EtOH (3
g/kg, intraperitoneally) following intermittent treatment in female (PND35)
adolescent mice. Inflammatory molecules, myelin proteins, and apoptotic markers
were assessed in the prefrontal cortex (PFC) and striatum/nucleus accumbens
(STR/NAcc). The effect of NF on alcohol drinking preference was evaluated in both
the wild-type and TLR4 knockout (KO) adolescent mice. Using astroglial cells, the
inhibitory potential of NT, NX, and NF on lipopolysaccharide (LPS), or the EtOH
triggered TLR4 response, was compared. RESULTS: Our findings indicate that NF
prevents the up-regulation of cytokines (IL-1beta, IL-17A, TNF-alpha), chemokines
(MCP-1, MIP-1, KC), and pro-inflammatory mediators (iNOS, COX-2), along with
myelin damage and apoptotic events, in both PFC and STR/NAcc. NF also abolishes
EtOH-induced escalation of alcohol preference/consumption, but has no effect when
administered to TLR4-KO mice. In vitro experiments indicate that NX and NF
inhibit TLR4 activation upon LPS or EtOH stimulation. Immunofluorescence studies
and lipid rafts isolation show that NF is able to prevent TLR4 translocation to
lipid rafts/caveolae in astrocytes. CONCLUSIONS: These results suggest that NF
prevents neuroinflammation and brain damage by blocking the TLR4 response and
also support the role of central pro-inflammatory immune signaling in the
modulation of alcohol consumption/addiction.
PMID- 28493565
TI - A new simple iterative reconstruction algorithm for SPECT transmission
measurement.
AB - This paper proposes a new iterative reconstruction algorithm for transmission
tomography and compares this algorithm with several other methods. The new
algorithm is simple and resembles the emission ML-EM algorithm in form. Due to
its simplicity, it is easy to implement and fast to compute a new update at each
iteration. The algorithm also always guarantees non-negative solutions.
Evaluations are performed using simulation studies and real phantom data.
Comparisons with other algorithms such as convex, gradient, and logMLEM show that
the proposed algorithm is as good as others and performs better in some cases.
PMID- 28493566
TI - Confirmation, refinement, and extension of a study in intrafraction motion
interplay with sliding jaw motion.
AB - The interplay between a constant scan speed and intrafraction oscillatory motion
produces interesting fluence intensity modulations along the axis of motion that
are sensitive to the motion function, as originally shown in a classic paper by
Yu et al. [Phys. Med. Biol. 43, 91-104 (1998)]. The fluence intensity profiles
are explored in this note for an intuitive understanding, then compared with Yu
et al., and finally further explored for the effects of low scan speed and random
components of both intrafraction and interfraction motion. At slow scan speeds
typical of helical tomotherapy, these fluence intensity modulations are only a
few percent. With the addition of only a small amount of cycle-to-cycle
randomness in frequency and amplitude, the fluence intensity profiles change
dramatically. It is further shown that after a typical 30-fraction treatment, the
sensitivities displayed in the single fraction fluence intensity profiles greatly
diminish.
PMID- 28493568
TI - A packed building-block compensator (TETRIS-RT) and feasibility for IMRT
delivery.
AB - A packed building-block compensator (TETRIS-RT) for IMRT (Intensity Modulated
Radiation Therapy) delivery has been proposed. The compensator contains two kinds
of cubic blocks: x-ray absorbing blocks for intensity modulation and x-ray
transparent blocks for packing. The packed blocks are placed inside a rectangular
enclosure, and the resulting compensators can be attached to a linac gantry head
through a rotatable mount for efficient multiportal IMRT. A fabrication device
and a sorting device were also developed. The fabrication device can
automatically stack two different types of blocks to produce a compensator while
the sorting device can separate each type of the blocks for subsequent
fabrication. Preliminary film experiments have shown that an additional leakage
dose through the rounded edges of the ten-layered x-ray absorbing blocks was 0.9%
of the delivered dose with a total shielded dose ratio of 10% including the peak
leakage. It was observed that the proposed compensator may provide a highly
modulated dose distribution. This suggests its feasibility for IMRT delivery with
a limit of 1cm*1cm spatial resolution at isocenter in the plane perpendicular to
the beam, and larger discrete intensity steps of approximately 10% compared to
conventional compensators. Advantages of the proposed compensator include that
the compensator blocks are reusable and can be utilized to automatically and
quickly fabricate a compensator, thereby minimizing human labor.
PMID- 28493567
TI - Semiautomated four-dimensional computed tomography segmentation using deformable
models.
AB - The purpose of this work is to demonstrate a proof of feasibility of the
application of a commercial prototype deformable model algorithm to the problem
of delineation of anatomic structures on four-dimensional (4D) computed
tomography (CT) image data sets. We acquired a 4D CT image data set of a
patient's thorax that consisted of three-dimensional (3D) image data sets from
eight phases in the respiratory cycle. The contours of the right and left lungs,
cord, heart, and esophagus were manually delineated on the end inspiration data
set. An interactive deformable model algorithm, originally intended for deforming
an atlas-based model surface to a 3D CT image data set, was applied in an
automated fashion. Triangulations based on the contours generated on each phase
were deformed to the CT data set on the succeeding phase to generate the contours
on that phase. Deformation was propagated through the eight phases, and the
contours obtained on the end inspiration data set were compared with the original
manually delineated contours. Structures defined by high-density gradients, such
as lungs, cord, and heart, were accurately reproduced, except in regions where
other gradient boundaries may have confused the algorithm, such as near bronchi.
The algorithm failed to accurately contour the esophagus, a soft-tissue structure
completely surrounded by tissue of similar density, without manual interaction.
This technique has the potential to facilitate contour delineation in 4D CT image
data sets; and future evolution of the software is expected to improve the
process.
PMID- 28493569
TI - Comparison of Monte Carlo calculations around a Fletcher Suit Delclos ovoid with
radiochromic film and normoxic polymer gel dosimetry.
AB - The Fletcher Suit Delclos (FSD) ovoids employed in intracavitary brachytherapy
(ICB) for cervical cancer contain shields to reduce dose to the bladder and
rectum. Many treatment planning systems (TPS) do not include the shields and
other ovoid structures in the dose calculation. Instead, TPSs calculate dose by
summing the dose contributions from the individual sources and ignoring ovoid
structures such as the shields. The goal of this work was to calculate the dose
distribution with Monte Carlo around a Selectron FSD ovoid and compare these
calculations with radiochromic film (RCF) and normoxic polymer gel dosimetry.
Monte Carlo calculations were performed with MCNPX 2.5.c for a single Selectron
FSD ovoid with and without shields. RCF measurements were performed in a plane
parallel to and displaced laterally 1.25 cm from the long axis of the ovoid.
MAGIC gel measurements were performed in a polymethylmethacrylate phantom. RCF
and MAGIC gel were irradiated with four 33MUGym2h-1 Cs-137 pellets for a period
of 24 h. Results indicated that MCNPX calculated dose to within +/-2% or 2 mm for
98% of points compared with RCF measurements and to within +/-3% or 3 mm for 98%
of points compared with MAGIC gel measurements. It is concluded that MCNPX 2.5.c
can calculate dose accurately in the presence of the ovoid shields, that RCF and
MAGIC gel can demonstrate the effect of ovoid shields on the dose distribution
and the ovoid shields reduce the dose by as much as 50%.
PMID- 28493570
TI - Use of simulated annealing for optimization of alignment parameters in limited
MRI acquisition volumes of the brain.
AB - Studies suggest that clinical outcomes are improved in repeat trigeminal
neuralgia (TN) Gamma Knife radiosurgery if a different part of the nerve from the
previous radiosurgery is treated. The MR images taken in the first and repeat
radiosurgery need to be coregistered to map the first radiosurgery volume onto
the second treatment planning image. We propose a fully automatic and robust
three-dimensional (3-D) mutual information- (MI-) based registration method
engineered by a simulated annealing (SA) optimization technique. Commonly,
Powell's method and Downhill simplex (DS) method are most popular in optimizing
the MI objective function in medical image registration applications. However,
due to the nonconvex property of the MI function, robustness of those two methods
is questionable, especially for our cases, where only 28 slices of MR T1 images
were utilized. Our SA method obtained successful registration results for all the
41 patients recruited in this study. On the other hand, Powell's method and the
DS method failed to provide satisfactory registration for 11 patients and 9
patients, respectively. The overlapping volume ratio (OVR) is defined to quantify
the degree of the partial volume overlap between the first and second MR scan.
Statistical results from a logistic regression procedure demonstrated that the
probability of a success of Powell's method tends to decrease as OVR decreases.
The rigid registration with Powell's or the DS method is not suitable for the TN
radiosurgery application, where OVR is likely to be low. In summary, our
experimental results demonstrated that the MI-based registration method with the
SA optimization technique is a robust and reliable option when the number of
slices in the imaging study is limited.
PMID- 28493571
TI - Dose perturbations due to contrast medium and air in MammoSite(r) treatment: An
experimental and Monte Carlo study.
AB - In the management of early breast cancer, a partial breast irradiation technique
called MammoSite(r) (Proxima Therapeutic Inc., Alpharetta, GA) has been advocated
in recent years. In MammoSite, a balloon implanted at the surgical cavity during
tumor excision is filled with a radio-opaque solution, and radiation is delivered
via a high dose rate brachytherapy source situated at the center of the balloon.
Frequently air may be introduced during placement of the balloon and/or injection
of the contrast solution into the balloon. The purpose of this work is to
quantify as well as to understand dose perturbations due to the presence of a
high-Z contrast medium and/or an air bubble with measurements and Monte Carlo
calculations. In addition, the measured dose distribution is compared with that
obtained from a commercial treatment planning system (Nucletron PLATO system).
For a balloon diameter of 42 mm, the dose variation as a function of distance
from the balloon surface is measured for various concentrations of a radio-opaque
solution (in the range 5%-25% by volume) with a small volume parallel plate ion
chamber and a micro-diode detector placed perpendicular to the balloon axis.
Monte Carlo simulations are performed to provide a basic understanding of the
interaction mechanism and the magnitude of dose perturbation at the interface
near balloon surface. Our results show that the radio-opaque concentration
produces dose perturbation up to 6%. The dose perturbation occurs mostly within
the distances <1mm from the balloon surface. The Plato system that does not
include heterogeneity correction may be sufficient for dose planning at distances
?10mm from the balloon surface for the iodine concentrations used in the
MammoSite procedures. The dose enhancement effect near the balloon surface (<1mm)
due to the higher iodine concentration is not correctly predicted by the Plato
system. The dose near the balloon surface may be increased by 0.5%percm3 of air.
Monte Carlo simulation suggests that the interface effect (enhanced dose near
surface) is primarily due to Compton electrons of short range (<0.5mm). For more
accurate dosimetry in MammoSite delivery, the dose perturbation due to the
presence of a radio-opaque contrast medium and air bubbles should be considered
in a brachytherapy planning system.
PMID- 28493572
TI - Effect of motion on tracer activity determination in CT attenuation corrected PET
images: A lung phantom study.
AB - Respiratory motion is known to affect the quantitation of FDG18 uptake in lung
lesions. The aim of the study was to investigate the magnitude of errors in
tracer activity determination due to motion, and its dependence upon CT
attenuation at different phases of the motion cycle. To estimate these errors we
have compared maximum activity concentrations determined from PET/CT images of a
lung phantom at rest and under simulated respiratory motion. The NEMA 2001 IEC
body phantom, containing six hollow spheres with diameters 37, 28, 22, 17, 13,
and 10 mm, was used in this study. To mimic lung tissue density, the phantom
(excluding spheres) was filled with low density polystyrene beads and water. The
phantom spheres were filled with FDG18 solution setting the target-to-background
activity concentration ratio at 8:1. PET/CT data were acquired with the phantom
at rest, and while it was undergoing periodic motion along the longitudinal axis
of the scanner with a range of displacement being 2 cm, and a period of 5 s. The
phantom at rest and in motion was scanned using manufacturer provided standard
helical/clinical protocol, a helical CT scan followed by a PET emission scan. The
moving phantom was also scanned using a 4D-CT protocol that provides volume image
sets at different phases of the motion cycle. To estimate the effect of motion on
quantitation of activities in six spheres, we have examined the activity
concentration data for (a) the stationary phantom, (b) the phantom undergoing
simulated respiratory motion, and (c) a moving phantom acquired with PET/4D-CT
protocol in which attenuation correction was performed with CT images acquired at
different phases of motion cycle. The data for the phantom at rest and in motion
acquired with the standard helical/clinical protocol showed that the activity
concentration in the spheres can be underestimated by as much as 75%, depending
on the sphere diameter. We have also demonstrated that fluctuations in sphere's
activity concentration from one PET/CT scan to another acquired with standard
helical/clinical protocol can arise as a consequence of spatial mismatch between
the sphere's location in PET emission and the CT data.
PMID- 28493573
TI - The applicability of simultaneous TRUS-CT imaging for the evaluation of prostate
seed implants.
AB - To study dose-effect relations of prostate implants with I-125 seeds, accurate
knowledge of the dose distribution in the prostate is essential. Commonly, a post
implant computed tomography (CT) scan is used to determine the geometry of the
implant and to delineate the contours of the prostate. However, the delineation
of the prostate on CT slices is very cumbersome due to poor contrast between the
prostate capsule and surrounding tissues. Transrectal Ultrasound (TRUS) on the
other hand offers good visualization of the prostate but poor visualization of
the implanted seeds. The purpose of this study was to investigate the
applicability of combining CT with 3D TRUS by means of image fusion. The
advantage of fused TRUS-CT imaging is that both prostate contours and implanted
seeds will be well visible. In our clinic, post-implant imaging was realized by
simultaneously acquiring a TRUS scan and a CT scan. The TRUS transducer was
inserted while the patient was on the CT couch and the CT scan was made directly
after the TRUS scan, with the probe still in situ. With the TRUS transducer being
visible on both TRUS and CT images, the geometrical relationship between both
image sets could be defined by registration on the transducer. Having proven the
applicability of simultaneous imaging, the accuracy of this registration method
was investigated by additional registration on visible seeds, after
preregistration on the transducer. In 4 out of 23 investigated cases an automatic
grey value registration on seeds failed for each of the investigated cost
functions, and in 2 cases for both cost functions, due to poor visibility of the
seeds on the TRUS scan. The average deviations of the seed registration with
respect to the transducer registration were negligible. However, in a few
individual cases the deviations were significant and probably due to movement of
the patient between TRUS and CT scan. In case of a registration on the transducer
it is important to avoid patient movement in-between the TRUS and CT scan and to
keep the time in-between the scans as short as possible. It can be concluded that
fusion of a CT scan and a simultaneously made TRUS scan by means of a three
dimensional (3D) transducer is feasible and accurate when performing a
registration on the transducer, if necessary, fine-tuned by a registration on
seeds. These fused images are likely to be of great value for post-implant dose
distribution evaluations.
PMID- 28493574
TI - Precise radiochromic film dosimetry using a flat-bed document scanner.
AB - In this study, a measurement protocol is presented that improves the precision of
dose measurements using a flat-bed document scanner in conjunction with two new
GafChromic(r) film models, HS and Prototype A EBT exposed to 6MV photon beams. We
established two sources of uncertainties in dose measurements, governed by
measurement and calibration curve fit parameters contributions. We have
quantitatively assessed the influence of different steps in the protocol on the
overall dose measurement uncertainty. Applying the protocol described in this
paper on the Agfa Arcus II flat-bed document scanner, the overall one-sigma dose
measurement uncertainty for an uniform field amounts to 2% or less for doses
above around 0.4Gy in the case of the EBT (Prototype A), and for doses above 5Gy
in the case of the HS model GafChromic(r) film using a region of interest 2*2mm2
in size.
PMID- 28493575
TI - Characterization and correction of temporal artifacts in CT.
AB - Image artifacts, caused by a temporally delayed response of a computed tomography
(CT) detector, were investigated. To study its consequences, a computer model for
a standard third generation CT scanner was devised and simulations were carried
out. Resulting image artifacts were studied for various voxel-based and
mathematical phantoms using three time constants, which characterize the delayed
signal responses of different detector configurations. Furthermore, a theory was
developed to understand temporal artifacts in reconstructed images. A filter
function was derived, which compensates for temporal artifacts. For a given
phantom, simulations and theory demonstrate that artifacts scale with the time
constant, characteristic for the detector, and the angular speed of the scanner.
PMID- 28493576
TI - Measurement of the detective quantum efficiency in digital detectors consistent
with the IEC 62220-1 standard: Practical considerations regarding the choice of
filter material.
AB - As part of a larger evaluation we attempted to measure the detective quantum
efficiency (DQE) of an amorphous silicon flat-panel detector using the method
described in the International Electrotechnical Commission standard 62220-1
published in October 2003. To achieve the radiographic beam conditions specified
in the standard, we purchased scientific-grade ultrahigh purity aluminum (99.999%
purity, type-11999 alloy) filters in thicknesses ranging from 0.1 through 10.0 mm
from a well-known, specialty metals supplier. Qualitative evaluation of flat
field images acquired at 71 kV (RQA5 beam quality) with 21 mm of ultrahigh purity
aluminum filtration demonstrated a low frequency mottle that was reproducible and
was not observed when the measurement was repeated at 74 kV (RQA5 beam quality)
with 21 mm of lower-purity aluminum (99.0% purity, type-1100 alloy) filtration.
This finding was ultimately attributed to the larger grain size (approximately 1
2 mm) of high purity aluminum metal, which is a well-known characteristic,
particularly in thicknesses greater than 1 mm. The impact of this low frequency
mottle is to significantly overestimate the noise power spectrum (NPS) at spatial
frequencies ?0.2mm-1, which in turn would cause an underestimation of the DQE in
this range. A subsequent evaluation of ultrahigh purity aluminum, purchased from
a second source, suggests, that reduced grain size can be achieved by the process
of annealing. Images acquired with this sample demonstrated vertical striated
nonuniformities that are attributed to the manufacturing method and which do not
appear to appreciably impact the NPS at spatial frequencies ?0.5mm-1, but do
result in an asymmetry in the x- and y-NPS at spatial frequencies ?0.2mm-1. Our
observations of markedly visible nonuniformities in images acquired with high
purity aluminum filtration suggest that the uniformity of filter materials should
be carefully evaluated and taken into consideration when measuring the DQE.
PMID- 28493577
TI - Design and application of an assessment protocol for electromagnetic tracking
systems.
AB - This paper defines a simple protocol for competitive and quantified evaluation of
electromagnetic tracking systems such as the NDI Aurora (A) and Ascension
microBIRD with dipole transmitter (B). It establishes new methods and a new
phantom design which assesses the reproducibility and allows comparability with
different tracking systems in a consistent environment. A machined base plate was
designed and manufactured in which a 50 mm grid of holes was precisely drilled
for position measurements. In the center a circle of 32 equispaced holes enables
the accurate measurement of rotation. The sensors can be clamped in a small mount
which fits into pairs of grid holes on the base plate. Relative
positional/orientational errors are found by subtracting the known
distances/rotations between the machined locations from the differences of the
mean observed positions/rotation. To measure the influence of metallic objects we
inserted rods made of steel (SST 303, SST 416), aluminum, and bronze into the
sensitive volume between sensor and emitter. We calculated the fiducial
registration error and fiducial location error with a standard stylus calibration
for both tracking systems and assessed two different methods of stylus
calibration. The positional jitter amounted to 0.14 mm(A) and 0.08 mm(B). A
relative positional error of 0.96mm+/-0.68mm, range -0.06 mm; 2.23 mm(A) and
1.14mm+/-0.78mm, range -3.72 mm; 1.57 mm(B) for a given distance of 50 mm was
found. The relative rotation error was found to be 0.51 degrees (A)/0.04 degrees
(B). The most relevant distortion caused by metallic objects results from SST
416. The maximum error 4.2mm(A)/?100mm(B) occurs when the rod is close to the
sensor(20 mm). While (B) is more sensitive with respect to metallic objects, (A)
is less accurate concerning orientation measurements. (B) showed a systematic
error when distances are calculated.
PMID- 28493578
TI - Internal radionuclide therapy: The ULMDOS software for treatment planning.
AB - Before therapy with unsealed radionuclides, a dosimetry assessment must be
performed for each patient. We present the interactive software tool ULMDOS,
which facilitates dosimetric calculations, enhances traceability, and adequate
documentation. ULMDOS is developed in IDL 6.1 (Interactive Data Language) under
Windows XP/2000. First the patient data, the radiotracer data, and optionally
urine and serum data are entered. After loading planar gamma camera images and
drawing regions of interest, the residence times can be calculated using fits of
the time activity data to exponential functions. Data can be saved in ASCII
format for retrospective examination and further processing. ULMDOS allows one to
process the dosimetric calculations within a standardized environment, spares the
time-consuming transfer of data between different software tools, enables the
documentation of ROI and raw data, and reduces intraindividual variability.
ULMDOS satisfies the required conditions for traceability and documentation as a
prerequisite to routine use in clinical settings.
PMID- 28493579
TI - Investigation of psychophysical measure for evaluation of similar images for
mammographic masses: Preliminary results.
AB - We investigated a psychophysical similarity measure for selection of images
similar to those of unknown masses on mammograms, which may assist radiologists
in the distinction between benign and malignant masses. Sixty pairs of masses
were selected from 1445 mass images prepared for this study, which were obtained
from the Digital Database for Screening Mammography by the University of South
Florida. Five radiologists provided subjective similarity ratings for these 60
pairs of masses based on the overall impression for diagnosis. Radiologists'
subjective ratings were marked on a continuous rating scale and quantified
between 0 and 1, which correspond to pairs not similar at all and pairs almost
identical, respectively. By use of the subjective ratings as "gold standard,"
similarity measures based on the Euclidean distance between pairs in feature
space and the psychophysical measure were determined. For determination of the
psychophysical similarity measure, an artificial neural network (ANN) was
employed to learn the relationship between radiologists' average subjective
similarity ratings and computer-extracted image features. To evaluate the
usefulness of the similarity measures, the agreement with the radiologists'
subjective similarity ratings was assessed in terms of correlation coefficients
between the average subjective ratings and the similarity measures. A commonly
used similarity measure based on the Euclidean distance was moderately correlated
(r=0.644) with the radiologists' average subjective ratings, whereas the
psychophysical measure by use of the ANN was highly correlated (r=0.798). The
preliminary result indicates that a psychophysical similarity measure would be
useful in the selection of images similar to those of unknown masses on
mammograms.
PMID- 28493580
TI - On the efficiency of photon beam treatment head simulations.
AB - The paper presents a theoretical derivation of the photon fluence simulation
efficiency in photon beam treatment head simulations without and with
bremsstrahlung splitting. The expressions obtained provide a rigorous explanation
of the efficiency dependence on scoring zone size and splitting number and
explain the larger efficiency of the directional bremsstrahlung splitting
technique compared to uniform bremsstrahlung splitting. They are also very useful
for determining the optimum splitting number in practical treatment head
simulations and for understanding the variation of simulation efficiency with
beam energy and field size.
PMID- 28493581
TI - Comparison of spirometry and abdominal height as four-dimensional computed
tomography metrics in lung.
AB - An important consideration in four-dimensional CT scanning is the selection of a
breathing metric for sorting the CT data and modeling internal motion. This study
compared two noninvasive breathing metrics, spirometry and abdominal height,
against internal air content, used as a surrogate for internal motion. Both
metrics were shown to be accurate, but the spirometry showed a stronger and more
reproducible relationship than the abdominal height in the lung. The abdominal
height was known to be affected by sensor placement and patient positioning while
the spirometer exhibited signal drift. By combining these two, a normalization of
the drift-free metric to tidal volume may be generated and the overall metric
precision may be improved.
PMID- 28493582
TI - The use of phase sequence image sets to reconstruct the total volume occupied by
a mobile lung tumor.
AB - The use of phase sequence image (PSI) sets to reveal the total volume occupied by
a mobile target is presented. Isocontrast composite clinical target volumes
(CCTVs) may be constructed from PSI sets in order to reveal the total volume
occupied by a mobile target during the course of its travel. The ability of the
CCTV technique to properly account for target motion is demonstrated by
comparison to contours of the true total volume occupied (TVO) for a number of
experimental phantom geometries. Finally, using real patient data, the clinical
utility of the CCTV technique to properly account for internal tumor motion while
minimizing the volume of healthy lung tissue irradiated is assessed by comparison
to the standard approach of applying safety margins. Results of the phantom study
reveal that CCTV cross sections constructed at the 20% isocontrast level yield
good agreement with the total cross sections (TXO) of mobile targets. These CCTVs
conform well to the TVOs of the moving targets examined whereby the addition of
small uniform margins ensures complete circumscription of the TVO with the
inclusion of minimal amounts of surrounding external volumes. The CCTV technique
is seen to be clearly superior to the common practice of the addition of safety
margins to individual CTV contours in order to account for internal target
motion. Margins required with the CCTV technique are eight to ten times smaller
than those required with individual CTVs.
PMID- 28493583
TI - Robust x-ray tubes for use within magnetic fields of MR scanners.
AB - A hybrid system that combines an x-ray fluoroscopic system and a magnetic
resonance (MR) system can provide physicians with the synergy of exquisite soft
tissue contrast (from MR) and high temporal and spatial resolutions (from x ray),
which may significantly benefit a number of image-guided interventional
procedures. However, the system configuration may require the x-ray tube to be
placed in a magnetic field, which can hinder the proper functioning of the x-ray
tube by deflecting its electron beam. From knowledge of how the magnetic field
affects the electron trajectories, we propose creating another magnetic field
along the cathode-anode axis using either solenoids or permanent magnets to
reduce the deflection of the electron beam for two cases: a strong and slightly
misaligned field or a weak field that is arbitrary in direction. Theoretical
analysis is presented and the electron beam is simulated in various external
magnetic fields with a finite element modeling program. Results show that both
correction schemes enhance the robustness of the x-ray tube operation in an
externally applied magnetic field.
PMID- 28493584
TI - Intracranial stereotactic positioning systems: Report of the American Association
of Physicists in Medicine Radiation Therapy Committee Task Group No. 68.
AB - Intracranial stereotactic positioning systems (ISPSs) are used to position
patients prior to precise radiation treatment of localized lesions of the brain.
Often, the lesion is located in close proximity to critical anatomic features
whose functions should be maintained. Many types of ISPSs have been described in
the literature and are commercially available. These are briefly reviewed. ISPS
systems provide two critical functions. The first is to establish a coordinate
system upon which a guided therapy can be applied. The second is to provide a
method to reapply the coordinate system to the patient such that the coordinates
assigned to the patient's anatomy are identical from application to application.
Without limiting this study to any particular approach to ISPSs, this report
introduces nomenclature and suggests performance tests to quantify both the
stability of the ISPS to map diagnostic data to a coordinate system, as well as
the ISPS's ability to be realigned to the patient's anatomy. For users who desire
to develop a new ISPS system, it may be necessary for the clinical team to
establish the accuracy and precision of each of these functions. For commercially
available systems that have demonstrated an acceptable level of accuracy and
precision, the clinical team may need to demonstrate local ability to apply the
system in a manner consistent with that employed during the published testing.
The level of accuracy and precision required of an individual ISPS system is
dependent upon the clinical protocol (e.g., fractionation, margin, pathology,
etc.). Each clinical team should provide routine quality assurance procedures
that are sufficient to support the assumptions of accuracy and precision used
during the planning process. The testing of ISPS systems can be grouped into two
broad categories, type testing, which occurs prior to general commercialization,
and site testing, performed when a commercial system is installed at a clinic.
Guidelines to help select the appropriate tests as well as recommendations to
help establish the required frequency of testing are provided. Because of the
broad scope of different systems, it is important that both the manufacturer and
user rigorously critique the system and set QA tests appropriate to the
particular device and its possible weaknesses. Major recommendations of the Task
Group include: introduction of a new nomenclature for reporting repositioning
accuracy; comprehensive analysis of patient characteristics that might adversely
affect positioning accuracy; performance of testing immediately before each
treatment to establish that there are no gross positioning errors; a general
request to the Medical Physics community for improved QA tools; implementation of
weekly portal imaging (perhaps cone beam CT in the future) as a method of
tracking fractionated patients (as per TG 40); and periodic routine reviews of
positioning accuracy.
PMID- 28493585
TI - Partial volume segmentation of brain magnetic resonance images based on maximum a
posteriori probability.
AB - Noise, partial volume (PV) effect, and image-intensity inhomogeneity render a
challenging task for segmentation of brain magnetic resonance (MR) images. Most
of the current MR image segmentation methods focus on only one or two of the
above-mentioned effects. The objective of this paper is to propose a unified
framework, based on the maximum a posteriori probability principle, by taking all
these effects into account simultaneously in order to improve image segmentation
performance. Instead of labeling each image voxel with a unique tissue type, the
percentage of each voxel belonging to different tissues, which we call a mixture,
is considered to address the PV effect. A Markov random field model is used to
describe the noise effect by considering the nearby spatial information of the
tissue mixture. The inhomogeneity effect is modeled as a bias field characterized
by a zero mean Gaussian prior probability. The well-known fuzzy C-mean model is
extended to define the likelihood function of the observed image. This framework
reduces theoretically, under some assumptions, to the adaptive fuzzy C-mean
(AFCM) algorithm proposed by Pham and Prince. Digital phantom and real clinical
MR images were used to test the proposed framework. Improved performance over the
AFCM algorithm was observed in a clinical environment where the inhomogeneity,
noise level, and PV effect are commonly encountered.
PMID- 28493586
TI - Plastic scintillation dosimetry: Optimal selection of scintillating fibers and
scintillators.
AB - Scintillation dosimetry is a promising avenue for evaluating dose patterns
delivered by intensity-modulated radiation therapy plans or for the small fields
involved in stereotactic radiosurgery. However, the increase in signal has been
the goal for many authors. In this paper, a comparison is made between plastic
scintillating fibers and plastic scintillator. The collection of scintillation
light was measured experimentally for four commercial models of scintillating
fibers (BCF-12, BCF-60, SCSF-78, SCSF-3HF) and two models of plastic
scintillators (BC-400, BC-408). The emission spectra of all six scintillators
were obtained by using an optical spectrum analyzer and they were compared with
theoretical behavior. For scintillation in the blue region, the signal intensity
of a singly clad scintillating fiber (BCF-12) was 120% of that of the plastic
scintillator (BC-400). For the multiclad fiber (SCSF-78), the signal reached 144%
of that of the plastic scintillator. The intensity of the green scintillating
fibers was lower than that of the plastic scintillator: 47% for the singly clad
fiber (BCF-60) and 77% for the multiclad fiber (SCSF-3HF). The collected light
was studied as a function of the scintillator length and radius for a cylindrical
probe. We found that symmetric detectors with nearly the same spatial resolution
in each direction (2 mm in diameter by 3 mm in length) could be made with a
signal equivalent to those of the more commonly used asymmetric scintillators.
With augmentation of the signal-to-noise ratio in consideration, this paper
presents a series of comparisons that should provide insight into selection of a
scintillator type and volume for development of a medical dosimeter.
PMID- 28493587
TI - Image-guided adaptive radiation therapy (IGART): Radiobiological and dose
escalation considerations for localized carcinoma of the prostate.
AB - The goal of this work was to evaluate the efficacy of various image-guided
adaptive radiation therapy (IGART) techniques to deliver and escalate dose to the
prostate in the presence of geometric uncertainties. Five prostate patients with
15-16 treatment CT studies each were retrospectively analyzed. All patients were
planned with an 18 MV, six-field conformal technique with a 10 mm margin size and
an initial prescription of 70 Gy in 35 fractions. The adaptive strategy employed
in this work for patient-specific dose escalation was to increase the
prescription dose in 2 Gy-per-fraction increments until the rectum normal tissue
complication probability (NTCP) reached a level equal to that of the nominal plan
NTCP (i.e., iso-NTCP dose escalation). The various target localization techniques
simulated were: (1) daily laser-guided alignment to skin tattoo marks that
represents treatment without image-guidance, (2) alignment to bony landmarks with
daily portal images, and (3) alignment to the clinical target volume (CTV) with
daily CT images. Techniques (1) and (3) were resimulated with a reduced margin
size of 5 mm to investigate further dose escalation. When delivering the original
clinical prescription dose of 70 Gy in 35 fractions, the "CTV registration"
technique yielded the highest tumor control probability (TCP) most frequently,
followed by the "bone registration" and "tattoo registration" techniques.
However, the differences in TCP among the three techniques were minor when the
margin size was 10 mm (?1.1%). Reducing the margin size to 5 mm significantly
degraded the TCP values of the "tattoo registration" technique in two of the five
patients, where a large difference was found compared to the other techniques
(?11.8%). The "CTV registration" technique, however, did maintain similar TCP
values compared to their 10 mm margin counterpart. In terms of normal tissue
sparing, the technique producing the lowest NTCP varied from patient to patient.
Reducing the margin size seemed the only sure way to reduce the NTCP
significantly, irrespective of the IGART technique employed. In escalating the
dose with the iso-NTCP constraint, the largest average gain in dose was observed
with the "tattoo registration" technique, followed by the "CTV registration" and
"bone registration" techniques. This is attributed to the fact that in three of
the five patients, the "tattoo registration" technique yielded the lowest NTCP,
hence a greater window of opportunity to escalate the dose was possible with this
technique. However, the variation among the five patients was also largest with
the "tattoo registration" technique where, in the case of one patient, the
required dose actually needed to be below the original prescription dose of 70 Gy
to satisfy the iso-NTCP constraint. This was not the case with the "CTV
registration" technique where positive and similar dose escalation was allowed on
all five patients. Based on these data, an attractive dose escalation strategy
may be to implement the "CTV registration" technique (for consistent dosimetric
coverage) for daily target localization in combination with a margin reduction
(for increased normal tissue sparing).
PMID- 28493588
TI - Ion recombination correction for very high dose-per-pulse high-energy electron
beams.
AB - The parallel-plate ionization chamber is the recommended tool for the absorbed
dose measurement in pulsed high-energy electron beams. Typically, the electron
beams used in radiotherapy have a dose-per-pulse value less then 0.1cGy/pulse. In
this range the factor to correct the response of an ionization chamber for the
lack of complete charge collection due to ion recombination (ksat) can be
properly evaluated with the standard "two voltage" method proposed by the
international dosimetric reports. Very high dose-per-pulse electron beams are
employed in some special Linac dedicated to the Intra-Operatory-Radiation-Therapy
(IORT). The high dose-per-pulse values (3-13cGy/pulse) characterizing the IORT
electron beams allow to deliver the therapeutic dose (10-20Gy) in less than a
minute. This considerably reduces the IORT procedure time, but some dosimetric
problems arise because the standard method to evaluate ksat overestimates its
value by 20%. Moreover, if the dose-per-pulse value >1cGy/pulse, the dependence
of ksat on the dose-per-pulse value cannot be neglected for relative dosimetry.
In this work the dependence of ksat on the dose-per-pulse value is derived, based
on the general equation that describes the ion recombination in the Boag theory.
A new equation for ksat, depending on known or measurable quantities, is
presented. The new ksat equation is experimentally tested by comparing the
absorbed doses to water measured with parallel-plate ionization chambers (Roos
and Markus) to that measured using dose-per-pulse independent dosimeters, such as
radiochromic films and chemical Fricke dosimeters. These measurements are
performed in the high dose-per-pulse (3-13cGy/pulse) electron beams of the IORT
dedicated Linac Hitesys Novac7 (Aprilia-Latina, Italy). The dose measurements
made using the parallel-plate chambers and those made using the dose-per-pulse
independent dosimeters are in good agreement (<3%). This demonstrates the
possibility of using the parallel-plate ionization chambers also for the very
high dose-per-pulse (>1cGy/pulse) electron-beam dosimetry.
PMID- 28493589
TI - Over the next decade the success of radiation treatment planning will be judged
by the immediate biological response of tumor cells rather than by surrogate
measures such as dose maximization and uniformity.
PMID- 28493590
TI - Brain SPECT with short focal-length cone-beam collimation.
AB - Single-photon emission-computed tomography (SPECT) imaging of deep brain
structures is compromised by loss of photons due to attenuation. We have
previously shown that a centrally peaked collimator sensitivity function can
compensate for this phenomenon, increasing sensitivity over most of the brain.
For dual-head instruments, parallel-hole collimators cannot provide variable
sensitivity without simultaneously degrading spatial resolution near the center
of the brain; this suggests the use of converging collimators. We have designed
collimator pairs for dual-head SPECT systems to increase sensitivity,
particularly in the center of the brain, and compared the new collimation
approach to existing approaches on the basis of performance in estimating
activity concentration of small structures at various locations in the brain. The
collimator pairs we evaluated included a cone-beam collimator, for increased
sensitivity, and a fan-beam collimator, for data sufficiency. We calculated
projections of an ellipsoidal uniform background, with 0.9-cm-radius spherical
lesions at several locations in the background. From these, we determined ideal
signal-to-noise ratios (SNRCRB) for estimation of activity concentration within
the spheres, based on the Cramer-Rao lower bound on variance. We also
reconstructed, by an ordered-subset expectation-maximization (OS-EM) procedure,
images of this phantom, as well as of the Zubal brain phantom, to allow visual
assessment and to ensure that they were free of artifacts. The best of the
collimator pairs evaluated comprised a cone-beam collimator with 20 cm focal
length, for which the focal point is inside the brain, and a fan-beam collimator
with 40 cm focal length. This pair yielded increased SNRCRB, compared to the
parallel-parallel pair, throughout the imaging volume. The factor by which SNRCRB
increased ranged from 1.1 at the most axially extreme location to 3.5 at the
center. The gains in SNRCRB were relatively robust to mismatches between the
center of the brain and the center of the imaging volume. Artifact-free
reconstructions of simulated data acquired using this pair were obtained.
Combining fan-beam and short-focusing cone-beam collimation should greatly
improve dual-head brain SPECT imaging, especially for centrally located
structures.
PMID- 28493591
TI - Transcatheter interventions in adults with congenital heart disease: Surveys from
the Society for Cardiovascular Angiography and Interventions to identify current
patterns of care and perception on training requirements.
AB - BACKGROUND: Interventional catheterization is central to the care of Adults with
Congenital Heart Disease (ACHD). Current standards for care provision and
training in ACHD intervention are lacking. We sought to examine trends in current
practice and training among interventionalists. METHODS: We analyzed the results
of two separate international surveys in June 2016. One was sent to all active
members from the Society of Cardiovascular Angiography and Interventions (SCAI)
who self-identified Structural Heart Disease or Congenital Heart Disease as a
practice area. The second survey was conducted through the Pediatric
Interventional Early Career Society (PICES) aimed at pediatric and adult
congenital interventionalists in their first seven years after training. The
total survey sample sizes were 1,535 and 112, respectively. RESULTS: Response
rates for the SCAI and PICES surveys were 15% (237/1,535) and 75% (84/112),
respectively. Most respondents (74%) worked at institutions with pediatric and
adult facilities in proximity (major medical centers). While 75% of SCAI
respondents believed complex transcatheter procedures should be performed by ACHD
trained interventionalists or multidisciplinary teams, only 32% reported such
care is being provided at the present time. Most pediatric and adult
cardiologists surveyed (73%) do not believe current interventional fellowships
provide adequate training for proficiency in ACHD interventions. CONCLUSIONS:
ACHD management remains underdeveloped in relative terms, particularly in the
United States. Significant gaps in interventional standards of practice and
future training needs were recognized by this study. Our survey should serve as
an impetus to establish training guidelines for physicians who seek to perform
ACHD interventions.
PMID- 28493592
TI - Experiences of outcome monitoring in service users with psychosis: Findings from
an Improving Access to Psychological Therapies for people with Severe Mental
Illness (IAPT-SMI) demonstration site.
AB - OBJECTIVES: Psychological therapy services are increasingly required to instate
routine outcome monitoring (ROM), to demonstrate the clinical and economic impact
of interventions. Professionals' views of ROM are an acknowledged barrier to
implementation. Service user perspectives have rarely been examined, but
acceptability and perceptions of ROM are critical to successful implementation.
We investigated service users' experiences of ROM in an Improving Access to
Psychological Therapies for people with Severe Mental Illness psychosis
demonstration site. DESIGN: ROM comprised a periodic assessment battery completed
at baseline, mid-therapy, and end-of-therapy and a single measure completed
session-by-session. Qualitative and quantitative feedback were sought at each
periodic ROM administration, and, for sessional ROM, at mid-therapy and end-of
therapy. Demographic and clinical correlates of satisfaction were examined cross
sectionally at baseline. Consistency of satisfaction over time and associations
of satisfaction with engagement were examined longitudinally. METHODS: Service
users rated baseline (n = 281/289), mid-therapy (n = 114/121), end-of-therapy (n
= 124/154), and session-by-session (mid-therapy n = 63/87 and end-of-therapy n =
90/123) ROM from 0 ('extremely unhelpful') to 10 ('extremely helpful') and gave
qualitative feedback. RESULTS: Service users predominantly found ROM helpful
(score 6-10; 64-72%) or neutral (score 5; 19-29%). Finding ROM less helpful was
associated with younger age and poorer general outcomes, but not with psychotic
symptoms or therapy dropout. Emerging qualitative themes included feeling
understood, valuing opportunities to reflect, expressing feelings, and tracking
progress towards goals. Shorter batteries would be preferable, particularly for
younger respondents, and those with poorer outcomes. CONCLUSIONS: ROM is
acceptable for people with psychosis. Tailoring assessments to specific subgroups
should be considered. PRACTITIONER POINTS: Routine outcome monitoring for
psychological therapy is acceptable to people with psychosis. Most respondents
experienced outcome monitoring as an opportunity to feel understood. Younger
people and those with poorer functioning and well-being might be at higher risk
of dissatisfaction. Short assessment batteries and less frequent outcome
monitoring might be preferable for some service users. Limitations of the study
Feedback about session-by-session outcome monitoring was not contemporaneous with
completion and may be subject to memory or other biases. Only two-thirds of
service users provided feedback about session-by-session ROM (compared to >94%
for periodic ROM) so findings may not be fully representative. Feedback about
measures was not provided anonymously, and it is possible that service users were
reluctant to express criticism about ROM to the assessor.
PMID- 28493593
TI - Superior parathyroid gland approach to the recurrent laryngeal nerve.
AB - BACKGROUND: The superior parathyroid gland is known to be almost constant in its
location under the false thyroid capsule. Could it be a landmark to point to the
site of incision of the false thyroid capsule and find the plane of the recurrent
laryngeal nerve (RLN) during thyroidectomy? METHODS: The study included 48
patients with benign goiter scheduled for hemithyroidectomy or total
thyroidectomy; there were 16 cases of solitary thyroid nodules, 27 cases of
multinodular goiter, and 5 cases of toxic goiter. RESULTS: This study included 80
lobectomies. All patients showed no evidence of postoperative RLN palsy,
bleeding, or hypoparathyroidism. The superior parathyroid gland was consistently
found within the false capsule in all cases, whereas the inferior parathyroid was
found within the same layer in 64 sides (80%). CONCLUSION: The described approach
can accurately guide dissection between true and false capsules of the thyroid to
reach and preserve both the RLN and the superior parathyroid gland. (c) 2017
Wiley Periodicals, Inc. Head Neck 39: 1287-1290, 2017.
PMID- 28493594
TI - Catalytic Asymmetric [3+1]-Cycloaddition Reaction of Ylides with Electrophilic
Metallo-enolcarbene Intermediates.
AB - The first asymmetric [3+1]-cycloaddition was successfully achieved by copper(I)
triflate/double-sidearmed bisoxazoline complex catalyzed reactions of beta
triisopropylsilyl-substituted enoldiazo compounds with sulfur ylides. This
methodology delivered a series of chiral cyclobutenes in good yields with high
enantio- and diastereoselectivities (up to 99 % ee, and >20:1 d.r.).
Additionally, the [3+1]-cycloaddition of catalytically generated metallo
enolcarbenes was successfully extended to reaction with a stable benzylidene
dichlororuthenium complex.
PMID- 28493596
TI - Overcoming the Tower of Babel in Medical Science by Finding the "EQUATOR":
Research Reporting Guidelines.
PMID- 28493595
TI - Empathy in paediatric intensive care nurses part 1: Behavioural and psychological
correlates.
AB - AIM: To determine if differences exist between paediatric intensive care nurses
and allied health professionals in empathy, secondary trauma, burnout, pain
exposure and pain ratings of self and others. Early and late career differences
were also examined. BACKGROUND: Nurses are routinely exposed to patient pain
expression. This work context may make them vulnerable to adverse outcomes such
as desensitization to patient pain or a compromise in personal well-being.
DESIGN: Cross-sectional study. METHODS: Data were collected from a convenience
sample of paediatric intensive care nurses (n = 27) and allied health
professionals (n = 24), from September 2014-June 2015, at a Canadian health
centre. Both groups completed one demographic and three behavioural scales.
Participants underwent fMRI while rating the pain of infant and adult patients in
a series of video clips. Data were analyzed using parametric and non-parametric
methods. fMRI results are reported in a second paper. RESULTS: Nurses were
significantly more likely to be exposed to pain at work than allied health
professionals and scored significantly higher on dimensions of empathy, secondary
trauma and burnout. Nurses scored their own pain and the pain of infant and adult
patients, higher than allied health participants. Less experienced nurses had
higher secondary trauma and burnout scores than more experienced nurses.
CONCLUSIONS: Paediatric intensive care work demands, such as patient pain
exposure, may be associated with nurse's higher report of empathy and pain in
self and others, but also with higher levels of secondary trauma and burnout,
when compared with allied health professionals.
PMID- 28493597
TI - R-warfarin anticoagulant effect.
PMID- 28493598
TI - Bystander Cardiopulmonary Resuscitation Is Clustered and Associated With
Neighborhood Socioeconomic Characteristics: A Geospatial Analysis of Kent County,
Michigan.
AB - OBJECTIVES: Geographic clustering of bystander cardiopulmonary resuscitation
(CPR) is associated with demographic and socioeconomic features of the community
where out-of-hospital cardiac arrest (OHCA) occurred, although this association
remains largely untested in rural areas. With a significant rural component and
relative racial homogeneity, Kent County, Michigan, provides a unique setting to
externally validate or identify new community features associated with bystander
CPR. Using a large, countywide data set, we tested for geographic clustering of
bystander CPR and its associations with community socioeconomic features.
METHODS: Secondary analysis of adult OHCA subjects (2010-2015) in the Cardiac
Arrest Registry to Enhance Survival (CARES) data set for Kent County, Michigan.
After linking geocoded OHCA cases to U.S. census data, we used Moran's I-test to
assess for spatial autocorrelation of population-weighted cardiac arrest rate by
census block group. Getis-Ord Gi statistic assessed for spatial clustering of
bystander CPR and mixed-effects hierarchical logistic regression estimated
adjusted associations between community features and bystander CPR. RESULTS: Of
1,592 subjects, 1,465 met inclusion criteria. Geospatial analysis revealed
significant clustering of OHCA in more populated/urban areas. Conversely,
bystander CPR was less likely in these areas (99% confidence) and more likely in
suburban and rural areas (99% confidence). Adjusting for clinical, demographic,
and socioeconomic covariates, bystander CPR was associated with public location
(odds ratio [OR] = 1.19; 95% confidence interval [CI] = 1.03-1.39), initially
shockable rhythms (OR = 1.48; 95% CI = 1.12-1.96), and those in urban
neighborhoods (OR = 0.54; 95% CI = 0.38-0.77). CONCLUSIONS: Out-of-hospital
cardiac arrest and bystander CPR are geographically clustered in Kent County,
Michigan, but bystander CPR is inversely associated with urban designation. These
results offer new insight into bystander CPR patterns in mixed urban and rural
regions and afford the opportunity for targeted community CPR education in areas
of low bystander CPR prevalence.
PMID- 28493600
TI - Endurance training selectively increases high-density lipoprotein-bound
sphingosine-1-phosphate in the plasma.
AB - Sphingosine-1-phosphate (S1P) is a bioactive lysosphingolipid that is found in
relatively high concentration in human plasma. Erythrocytes, endothelial cells,
and activated platelets are the main sources of circulating S1P. The majority of
plasma S1P is transported bound to high-density lipoprotein (HDL) and albumin. In
recent years, HDL-bound S1P attracted much attention due to its cardioprotective
and anti-atherogenic properties. We have previously found that endurance-trained
athletes are characterized by higher plasma S1P concentration compared to
untrained individuals. This finding prompted us to examine the effect of
endurance training on S1P metabolism in blood. Thirteen healthy, untrained, male
subjects completed an 8-week training program on a rowing ergometer. Three days
before the first, and 3 days after the last training session, blood samples were
drawn from an antecubital vein. We found that total plasma S1P concentration was
increased after the training. Further analysis of different plasma fractions
showed that the training selectively elevated HDL-bound S1P. This effect was
associated with activation of sphingosine kinase in erythrocytes and platelets
and enhanced S1P release from red blood cells. We postulate that increase in HDL
bound S1P level is one of the mechanisms underlying beneficial effects of regular
physical activity on cardiovascular diseases.
PMID- 28493599
TI - Spinal Cord Stimulator Implant Infection Rates and Risk Factors: A Multicenter
Retrospective Study.
AB - OBJECTIVES: Spinal cord stimulation is an evidence-based treatment for a number
of chronic pain conditions. While this therapy offers improvement in pain and
function it is not without potential complications. These complications include
device failure, migration, loss of therapeutic paresthesia, and infection. This
article looked to establish a modern infection rate for spinal cord stimulators,
assess the impact of known risk factors for surgical site infections and to
determine the impact of certain preventative measures on the rate of infection.
METHODS: After institutional review board approval, a multisite, retrospective
review was conducted on 2737 unique implants or revisions of SCS systems. Patient
demographics, risk factors including diabetes, tobacco use, obesity, revision
surgery, trial length, implant location, implant type, surgeon background,
prophylactic antibiotic use, utilization of a occlusive dressing, and post
operative antibiotic use were recorded and analyzed. RESULTS: The overall
infection rate was 2.45% (n = 67). Diabetes, tobacco use, and obesity did not
independently increase the rate of infection. Revision surgeries had a trend
toward higher infection rate; however, this did not meet statistical
significance. There was no difference in the rate of infection between implants
performed by physicians of different base specialties, cylinder leads vs. paddle
leads, or between different prophylactic antibiotics. Implants performed at
academic centers had a higher rate of infection when compared to implants
performed in nonacademic settings. When patients received an occlusive dressing
or post-operative antibiotics they had a lower rate of infection. CONCLUSIONS:
The infection rate (2.45%) reported in this study is lower than the previously
reported rates (3-6%) and are on par with other surgical specialties. This study
did not show an increased rate of infection for patients that used tobacco, had
diabetes or were obese. It's possible that given the low overall infection rate a
larger study is needed to establish the true impact of these factors on
infection. In addition, this study did not address the impact of poorly
controlled diabetes mellitus (elevated hemoglobin A1c) vs. well-controlled
diabetes. It can be concluded from this study that utilizing an occlusive
dressing over the incision in the post-operative period decreases the rate of
infection and should become the standard of care. This study also demonstrated
the positive impact of post-operative antibiotics in decreasing the rate of
infection. Studies in other surgical specialties have not shown this impact which
would suggest that further research is needed.
PMID- 28493601
TI - Accommodating interruptions: A grounded theory of young people with asthma.
AB - AIMS AND OBJECTIVES: The aim of this study was to develop an explanatory theory
on the lives of young people with asthma, issues affecting them and the impact of
asthma on their day-to-day lives. BACKGROUND: Accommodating Interruptions is a
theory that explains young people's concerns about living with asthma. Although
national and international asthma management guidelines exist, it is accepted
that the symptom control of asthma among the young people population is poor.
DESIGN: This study was undertaken using Classic Grounded Theory. METHODS: Data
were collected through in-depth interviews and clinic consultations with young
people aged 11-16 years who had asthma for over 1 year. Data were also collected
from participant diaries. Constant comparative analysis, theoretical coding and
memo writing were used to develop the substantive theory. RESULTS: The theory
explains how young people resolve their main concern of being restricted by
Accommodating Interruptions in their lives. They do this by assimilating
behaviours in balance finding, moderating influence, fitting in and assuming
control minimising the effects of asthma on their everyday lives. CONCLUSION: The
theory of Accommodating Interruptions explains young people's asthma management
behaviours in a new way. It allows us to understand how and why young people
behave the way they do because they want to participate and be included in
everyday activities, events and relationships. The theory adds to the body of
knowledge on how young people with asthma live their day-to-day lives and it
challenges some existing viewpoints in the literature regarding their behaviours.
RELEVANCE TO CLINICAL PRACTICE: The findings have implications for developing
services to support young people in a more meaningful way as they accommodate the
interruptions associated with asthma in their lives.
PMID- 28493602
TI - Avenacosides: Metabolism, and potential use as exposure biomarkers of oat intake.
AB - SCOPE: Exposure biomarkers used for objective estimation of whole-grain (WG)
intake are essential for epidemiologic studies of WG consumption, however, up to
now, no exposure biomarkers were developed for WG oat intake. This study
investigates the potential of oat unique components, Avenacoside-B (AVE-B) and -A
(AVE-A), as exposure biomarkers of oat intake. METHODS AND RESULTS: An in vivo
study performed in mice and an in vitro batch fecal fermentation study were used
to investigate the potential metabolic routes of AVE-B and -A. Twelve healthy
volunteers were recruited in the human urinary pharmacokinetic study, each
participant received a single dose of oat bran as breakfast, 48 h urine samples
were collected at baseline and after treatment period, and AVE-B and -A were
quantified by LC-MS/MS. Deglycosylation metabolic route was identified as the
major metabolic path for AVE-B and -A. Urinary AVE-B and -A concentrations
increased rapidly after oat ingestion, reached their maximum excretion rates
(ERmax ) fairly simultaneously within 5 h, then decreased gradually. And the mean
eliminate half-lives (T1/2 ) for AVE-B and -A were determined as 6.22 and 4.55 h,
respectively. CONCLUSION: Oat AVE-B and -A have great potential to be used as
specific exposure biomarkers to reflect oat intake.
PMID- 28493603
TI - Age-related endothelial dysfunction in human skeletal muscle feed arteries: the
role of free radicals derived from mitochondria in the vasculature.
AB - AIM: This study sought to determine the role of free radicals derived from
mitochondria in the vasculature in the recognized age-related endothelial
dysfunction of human skeletal muscle feed arteries (SMFAs). METHODS: A total of
44 SMFAs were studied with and without acute exposure to the mitochondria
targeted antioxidant MitoQ and nitric oxide synthase (NOS) blockade. The relative
abundance of proteins from the electron transport chain, phosphorylated (p-) to
endothelial (e) NOS ratio, manganese superoxide dismutase (MnSOD) and the
mitochondria-derived superoxide (O2-) levels were assessed in SMFA. Endothelium
dependent and endothelium-independent SMFA vasodilation was assessed in response
to flow-induced shear stress, acetylcholine (ACh) and sodium nitroprusside (SNP).
RESULTS: MitoQ restored endothelium-dependent vasodilation in the old to that of
the young when stimulated by both flow (young: 68 +/- 5; old: 25 +/- 7; old +
MitoQ 65 +/- 9%) and ACh (young: 97 +/- 4; old: 59 +/- 10; old + MitoQ: 98 +/-
5%), but did not alter the initially uncompromised, endothelium-independent
vasodilation (SNP). Compared to the young, MitoQ in the old diminished the
initially elevated mitochondria-derived O2- levels and appeared to attenuate the
breakdown of MnSOD. Furthermore, MitoQ increased the ratio of p-eNOS to NOS and
the restoration of endothelium-dependent vasodilation in the old by MitoQ was
ablated by NOS blockade. CONCLUSION: This study demonstrated that MitoQ reverses
age-related vascular dysfunction by what appears to be an NO-dependent mechanism
in human SMFAs. These findings suggest that mitochondria-targeted antioxidants
may have utility in terms of counteracting the attenuated blood flow and vascular
dysfunction associated with advancing age.
PMID- 28493604
TI - CIC break-apart fluorescence in-situ hybridization misses a subset of CIC-DUX4
sarcomas: a clinicopathological and molecular study.
AB - AIMS: Approximately 60-70% of high-grade round-cell sarcomas that lack the Ewing
sarcoma breakpoint region 1 (EWSR1) rearrangement harbour a rearrangement of the
CIC gene, most commonly CIC-DUX4. Recent studies have established that CIC
rearranged sarcomas constitute a distinct group characterized by recognizable
histology and immunoprofiles, such as positivity for ETV4 and WT1 and negativity
for NKX2.2. Although these sarcomas are diagnosed increasingly in practice by
fluorescence in-situ hybridization (FISH) with CIC break-apart probes, the
optimal modality to diagnose these sarcomas has not been determined. In this
study, we describe four round-cell sarcomas that showed false-negative results by
CIC break-apart FISH assays. METHODS AND RESULTS: These sarcomas showed
characteristic histology of CIC-rearranged sarcomas, and all were
immunohistochemically positive for ETV4 and WT1 and negative for NKX2.2. Although
FISH showed non-atypical negative signals for CIC rearrangement, high-throughput
RNA sequencing identified CIC-DUX4 and its fusion breakpoint in all cases. Their
clinical and histological findings, as well as fusion points determined by RNA
sequencing, did not differ significantly from those of nine FISH-positive CIC
DUX4 sarcoma cases. We estimated that the FISH false-negative rate for CIC
rearranged sarcomas was 14%. Although neither histology nor immunoprofiles (e.g.
ETV4 and WT1) are entirely sensitive or specific for CIC-rearranged sarcomas, the
observation that these four cases were identified successfully by such phenotypes
suggested their practical utility. CONCLUSIONS: CIC break-apart FISH assays
missed a significant minority of CIC-DUX4 sarcomas, and full awareness of typical
morphology and judicious immunohistochemical work-ups, including analyses of ETV4
and WT1, should complement diagnostic assessment.
PMID- 28493606
TI - MicroRNAs as potential biomarkers to predict the risk of urinary retention
following intradetrusor onabotulinumtoxin-A injection.
AB - AIMS: MicroRNAs (miRs) control post-transcriptional gene expression, and this is
relevant in understanding better chronic diseases and treatment outcomes. The
role of miRs in the pathology and treatment outcomes of overactive bladder (OAB)
is unknown. In this study, we assessed the differential expression of miRs in OAB
patients responding with either normal or elevated post-void residual volumes
(PVRs) >=200 mL following intradetrusor injection of onabotulinumtoxin-A (onaBoNT
A). METHODS: Female OAB patients refractory to OAB drugs were consented for this
study. Cystoscopic-guided punch bladder biopsy was obtained at the time of
injection of onaBoNT-A 100 units. The expression of 13 miR species, selected for
their known effect on neurotrophin expression and smooth muscle function, was
measured. PVRs and urine nerve growth factor (NGF) levels were measured at
baseline and at the follow-up visit. RESULTS: Fourteen patients with mean age of
66 years were consented. Of these patients, nine maintained PVRs <200 mL after
onaBoNT-A injection to comprise the low PVR group. The other five patients with
PVRs >=200 mL comprised the high PVR group. The expression of miR221 and miR125b
was upregulated by 11- and 2-fold, respectively, in patients who responded with
low PVRs after onaBoNT-A (P < 0.05). Urine NGF levels at baseline were not
different between the two groups. CONCLUSIONS: This study suggests that
deficiency in the pretreatment expression of miR221 and miR125b may predispose
OAB patients to high PVRs following intradetrusor onaBoNT-A. Additional studies
are needed to better understand the role of miRs in OAB.
PMID- 28493605
TI - Adverse effects of obesity on cognitive functions in individuals at ultra high
risk for bipolar disorder: Results from the global mood and brain science
initiative.
AB - BACKGROUND: The burden of illness associated with bipolar disorder (BD) warrants
early pre-emption/prevention. Prediction models limited to psychiatric
phenomenology have insufficient predictive power. Herein, we aimed to evaluate
whether the presence of overweight/obesity is associated with greater cognitive
decline in individuals at high risk (HR) or ultra high risk (UHR) for BD.
METHODS: We conducted a retrospective analysis to investigate the moderational
role of body mass index (BMI) on measures of cognitive function. Subjects between
the ages of 8 and 28 years with a positive family history of BD were compared to
age-matched controls with a negative family history of BD. Subjects with at least
one biological parent with bipolar I/II disorder were further stratified into UHR
or HR status by the presence or absence, respectively, of subthreshold hypomanic,
major depressive, attenuated psychotic, and/or attention-deficit/hyperactivity
disorder symptoms. RESULTS: A total of 36 individuals at HR for BD, 33
individuals at UHR for BD, and 48 age-matched controls were included in the
analysis. Higher BMI was significantly associated with lower performance on
measures of processing speed (i.e. Brief Assessment of Cognition in Schizophrenia
symbol coding: r=-.186, P=.047) and attention/vigilance (i.e. Continuous
Performance Test-Identical Pairs: r=-.257, P=.006). There were trends for
negative correlations between BMI and measures of working memory (i.e. Wechsler
Memory Scale-III Spatial Span: r=-0.177, P=.059) and overall cognitive function
(i.e. Measurement and Treatment Research to Improve Cognition in Schizophrenia
composite score: r=-.157, P=.097). Negative associations between BMI and
cognitive performance were significantly stronger in the UHR group than in the HR
group, when compared to controls. CONCLUSIONS: Individuals at varying degrees of
risk for BD exhibit greater cognitive impairment as a function of co-existing
overweight/obesity. Prediction models for BD may be substantively informed by
including information related to overweight/obesity and, perhaps, other general
medical conditions that share pathology with BD. Our findings herein, as well as
the salutary effects of bariatric surgery on measures of cognitive function in
obese populations, provide the rationale for hypothesizing that mitigating excess
weight in individuals at elevated risk for BD may forestall or prevent
declaration of illness.
PMID- 28493607
TI - Rhodium-Catalyzed Addition of Aryl Boronic Acids to 2,2-Disubstituted
Malononitriles.
AB - beta-Ketonitriles bearing a quaternary carbon at the 2-position were prepared
through Rh-catalyzed addition of aryl boronic acids to 2,2-disubstituted
malononitriles. In contrast to the previously described transnitrilative
cyanation of aryl boronic acids with dialkylmalononitriles, the present reaction
avoids retro-Thorpe collapse of the intermediate addition product through the use
of a milder base. The reaction was amenable to a variety of aryl boronic acids
and disubstituted malononitriles, providing a diverse array of beta-ketonitriles.
The products could be further derivatized to valuable chiral alpha,alpha
disubstituted-beta-aminonitriles through addition reactions to the corresponding
N-tert-butanesulfinyl imines.
PMID- 28493609
TI - Second cancer risk assessments after involved-site radiotherapy for mediastinal
Hodgkin lymphoma.
AB - PURPOSE: This study was conducted to provide second cancer risk assessments
attributable to involved-site radiotherapy (ISRT) of mediastinal Hodgkin lymphoma
(HL) and to compare these risks with those from the conventional involved-field
radiation therapy (IFRT). METHODS: Both ISRT and IFRT plans were made for 11
patients (six females, five males) with HL in the region of mediastinum. All
three-dimensional plans involved 6 MV photon beams and delivered 30 Gy to the
target site. Differential dose-volume histograms were defined for the lung,
female breast, and esophagus which were partly included within the planned
treatment fields. The patient-specific organ equivalent dose (OED) and the
relevant lifetime attributable risk (LAR) of developing malignancies in each of
the above critical organs were determined with the aid of a mechanistic, plateau
and bell-shaped models. The LAR estimates were compared with the baseline risks
for unexposed people. RESULTS: The OED range of lung, breast, and esophagus
calculated by the ISRT plans was 176.1-360.2, 19.5-124.1, and 42.6-157.7 cGy,
respectively. The resultant LARs of developing lung and breast cancer as
estimated by the three different models were at least 1.8 and 5.3 times lower
than the baseline risks, respectively. The probability for the appearance of
radiation-induced esophageal malignancies from ISRT in males was also up to 3.8
times smaller than the nominal incidence cancer rates. The corresponding
probability in irradiated females exceeded the baseline risks. The estimated
lifetime risks for lung and breast cancer induction due to ISRT were
systematically and significantly lower than those from the IFRT irrespective of
the model used for analysis (P < 0.05). No significant difference was found
between the LARs for esophageal cancer development estimated by the ISRT and IFRT
plans (P = 0.63). CONCLUSIONS: The presented second cancer risk data may be of
value in the selection of the optimal radiotherapy technique for the management
of mediastinal HL and in the subsequent follow-up of irradiated patients.
PMID- 28493610
TI - Fractionated aliphatic alcohols as synthetic precursors of ultra long-chain
monoacylglycerols for cosmetic applications.
AB - BACKGROUND: Xerosis is an abnormally dry and flaky skin condition that is
associated with a change in the packing behaviour of the lipid matrix in the
stratum corneum (SC), the outermost layer of the skin. This skin condition can
lead to an increase in transepidermal water loss (TEWL). As ultralong-chain fatty
acids have a positive effect on maintaining the packing behaviour of the SC lipid
matrix, a moisturizer which contains glycerides of ultralong-chain fatty acids
could act as a semi-occlusive layer on the surface of the skin. This will lower
the rate of water evaporation through the epidermis and consequently help prevent
or improve skin xerosis. OBJECTIVE: To identify a novel source of ultralong-chain
lipids and develop monoacylglycerols with mixed fatty acyl chain lengths that
have occlusive properties superior to petrolatum. METHODS: Initially, Performacol
425, a mixture of very long-chain fatty alcohols, was fractionated using short
path distillation to yield a fraction enriched with C22:0-C26:0 fatty alcohols.
The fatty alcohol fraction was then oxidized using Jones reagent, and the
resulting fatty acids were esterified with glycerol to yield the corresponding
monoglycerides using Novozym 435. These were then evaluated using Fourier
transform infrared spectroscopy, differential scanning calorimetry and water
vapour transmission rate measurements. RESULTS: The monoacylglycerols enriched
with C22:0-C26:0 displayed a melting point of 80 degrees C and orthorhombic
packing; packing behaviour mainly present in healthy SC. In addition, a
phospholipid-structured emulsion containing 3% of the monoglycerides displayed
occlusive properties superior to the vehicle containing 3% petrolatum jelly.
CONCLUSIONS: Performacol 425 can be a potential source of fatty alcohols to
synthesize monoacylglycerols that can improve the occlusive behaviour of
phospholipid-structured emulsions.
PMID- 28493608
TI - The Epidemiology of Emergency Department Trauma Discharges in the United States.
AB - OBJECTIVE: Injury-related morbidity and mortality is an important emergency
medicine and public health challenge in the United States. Here we describe the
epidemiology of traumatic injury presenting to U.S. emergency departments (EDs),
define changes in types and causes of injury among the elderly and the young,
characterize the role of trauma centers and teaching hospitals in providing
emergency trauma care, and estimate the overall economic burden of treating such
injuries. METHODS: We conducted a secondary retrospective, repeated cross
sectional study of the Nationwide Emergency Department Data Sample (NEDS), the
largest all-payer ED survey database in the United States. Main outcomes and
measures were survey-adjusted counts, proportions, means, and rates with
associated standard errors (SEs) and 95% confidence intervals. We plotted annual
age-stratified ED discharge rates for traumatic injury and present tables of
proportions of common injuries and external causes. We modeled the association of
Level I or II trauma center care with injury fatality using a multivariable
survey-adjusted logistic regression analysis that controlled for age, sex, injury
severity, comorbid diagnoses, and teaching hospital status. RESULTS: There were
181,194,431 (SE = 4,234) traumatic injury discharges from U.S. EDs between 2006
and 2012. There was a mean year-to-year decrease of 143 (95% CI = -184.3 to
68.5) visits per 100,000 U.S. population during the study period. The all-age,
all-cause case-fatality rate for traumatic injuries across U.S. EDs during the
study period was 0.17% (SE = 0.001%). The case-fatality rate for the most
severely injured averaged 4.8% (SE = 0.001%), and severely injured patients were
nearly four times as likely to be seen in Level I or II trauma centers (relative
risk = 3.9 [95% CI = 3.7 to 4.1]). The unadjusted risk ratio, based on group
counts, for the association of Level I or II trauma centers with mortality was
risk ratio = 4.9 (95% CI = 4.5 to 5.3); however, after sex, age, injury severity,
and comorbidities were accounted for, Level I or II trauma centers were not
associated with an increased risk of fatality (odds ratio = 0.96 [95% CI = 0.79
to 1.18]). There were notable changes at the extremes of age in types and causes
of ED discharges for traumatic injury between 2009 and 2012. Age-stratified rates
of diagnoses of traumatic brain injury increased 29.5% (SE = 2.6%) for adults
older than 85 and increased 44.9% (SE = 1.3%) for children younger than 18.
Firearm-related injuries increased 31.7% (SE = 0.2%) in children 5 years and
younger. The total inflation-adjusted cost of ED injury care in the United States
between 2006 and 2012 was $99.75 billion (SE = $0.03 billion). CONCLUSIONS:
Emergency departments are a sensitive barometer of the continuing impact of
traumatic injury as an important cause of morbidity and mortality in the United
States. Level I or II trauma centers remain a bulwark against the tide of severe
trauma in the United States, but the types and causes of traumatic injury in the
United States are changing in consequential ways, particularly at the extremes of
age, with traumatic brain injuries and firearm-related trauma presenting
increased challenges.
PMID- 28493611
TI - Fucoidan ameliorates pancreatic beta-cell death and impaired insulin synthesis in
streptozotocin-treated beta cells and mice via a Sirt-1-dependent manner.
AB - SCOPE: Several beneficial biological functions of fucoidan (FO) isolated from
brown algae have been demonstrated. The purpose of this study was to investigate
whether FO derived from Sargassum hemiphyllum ameliorates pancreatic beta-cell
damage and impaired insulin synthesis under diabetic condition. METHODS AND
RESULTS: The effects of FO were studied in streptozotocin (STZ)-treated
pancreatic beta-cell line, NIT-1cells, and mice. The cell apoptosis, protein
analyses, histological examination, and pancreatic function assays were
performed. The increased pancreatic beta-cell apoptosis and decreased insulin
secretion observed in STZ-treated NIT-1 cells and mice were greatly attenuated by
FO. Moreover, FO has an ability to enhance glucagon-like peptide-1 receptor (GLP
1R) and sirtuin 1 (Sirt-1) activity through activation of AMPK/GAPDH/PDX-1
cascade in STZ-treated beta cells. However, the effects of FO were significantly
reversed by EX527, a specific Sirt-1 inhibitor. Similarly, the hyperglycemia,
lower expression of Sirt-1, PDX-1, and GLP-1R in the pancreas of diabetic mice
were markedly improved after FO administration. CONCLUSION: We demonstrated that
FO exhibits an anti-diabetic effect mainly through attenuation of beta-cell
death, thereby elevating insulin synthesis by upregulating PDX-1 and GLP1-R via a
Sirt-1-dependent manner. Therefore, FO-containing food or supplements may have a
therapeutic effect for diabetes by preventing beta-cell damage and dysfunction.
PMID- 28493612
TI - Identification of extracellular matrix protein 1 as a potential plasma biomarker
of ESCC by proteomic analysis using iTRAQ and 2D-LC-MS/MS.
AB - PURPOSE: This study was aimed to conduct a proteomics profiling analysis on
plasma obtained from ESCC patients with the goal of identifying appropriate
plasma protein biomarkers in the progression of ESCC. EXPERIMENTAL DESIGN: Plasma
from 28 ESCC patients and 28 healthy controls (HC) were analyzed by iTRAQ
combined with 2D-LC-MS/MS. ProteinPilot software was used to identify the
differentially expressed plasma proteins in ESCC compared to HC. Western blot was
performed to verify the expression of selected proteins in 37 independent ESCC
patients and 37 HC. Transwell and MTT assays were used to detect the biological
function of ECM1 protein in vitro. RESULTS: Nineteen (four upregulated and
fifteen downregulated) proteins were identified as differentially expressed
between ESCC and HC (p <0.05). Biological functions of these proteins are
involved in cell adhesion, cell apoptosis and metabolic processes, visual
perception and immune response. Of these, extracellular matrix 1 (ECM1) and
lumican (LUM) were selected further confirmation by Western blot (p <0.05), which
were consistent with the iTRAQ results. Furthermore, the migration ability of
EC9706 cell line after overexpressing ECM1 was increased significantly (p <0.05).
The proliferation ability of HUVEC cell was enhanced when treated with the
culture supernatants of EC9706 overexpressed ECM1(p <0.05). CONCLUSION AND
CLINICAL RELEVANCE: This proteome analysis indicate that ECM1 is a potential
novel plasma protein biomarker for the detection of primary ESCC and evaluation
of neoplasms progression.
PMID- 28493613
TI - Subtle blood-brain barrier leakage rate and spatial extent: Considerations for
dynamic contrast-enhanced MRI.
AB - PURPOSE: Dynamic contrast-enhanced (DCE) MRI can be used to measure blood-brain
barrier (BBB) leakage. In neurodegenerative disorders such as small vessel
disease and dementia, the leakage can be very subtle and the corresponding signal
can be rather noisy. For these reasons, an optimized DCE-MRI measurement and
study design is required. To this end, a new measure indicative of the spatial
extent of leakage is introduced and the effects of scan time and sample size are
explored. METHODS: Dual-time resolution DCE-MRI was performed in 16 patients with
early Alzheimer's disease (AD) and 17 healthy controls. The leakage rate (Ki )
and volume fraction of detectable leaking tissue (vL ) to quantify the spatial
extent of BBB leakage were calculated in cortical gray matter and white matter
using noise-corrected histogram analysis of leakage maps. Computer simulations
utilizing realistic Ki histograms, mimicking the strong effect of noise and
variation in Ki values, were performed to understand the influence of scan time
on the estimated leakage. RESULTS: The mean Ki was very low (order of 10-4 min-1
) and highly influenced by noise, causing the Ki to be increasingly overestimated
at shorter scan times. In the white matter, the Ki was not different between
patients with early AD and controls, but was higher in the cortex for patients,
reaching significance after 14.5 min of scan time. To detect group differences,
vL proved more suitable, showing significantly higher values for patients
compared with controls in the cortex after 8 minutes of scan time, and in white
matter after 15.5 min. CONCLUSIONS: Several ways to improve the sensitivity of a
DCE-MRI experiment to subtle BBB leakage were presented. We have provided vL as
an attractive and potentially more time-efficient alternative to detect group
differences in subtle and widespread blood-brain barrier leakage compared with
leakage rate Ki . Recommendations on group size and scan time are made based on
statistical power calculations to aid future research.
PMID- 28493614
TI - Accuracy of Physical Examination, Ankle-Brachial Index, and Ultrasonography in
the Diagnosis of Arterial Injury in Patients With Penetrating Extremity Trauma: A
Systematic Review and Meta-analysis.
AB - BACKGROUND: Penetrating Extremity Trauma (PET) may result in arterial injury, a
rare but limb- and life-threatening surgical emergency. Timely, accurate
diagnosis is essential for potential intervention in order to prevent significant
morbidity. OBJECTIVES: Using a systematic review/meta-analytic approach, we
determined the utility of physical examination, Ankle-Brachial Index (ABI), and
Ultrasonography (US) in the diagnosis of arterial injury in emergency department
(ED) patients who have sustained PET. We applied a test-treatment threshold model
to determine which evaluations may obviate CT Angiography (CTA). METHODS: We
searched PubMed, Embase, and Scopus from inception to November 2016 for studies
of ED patients with PET. We included studies on adult and pediatric subjects. We
defined the reference standard to include CTA, catheter angiography, or surgical
exploration. When low-risk patients did not undergo the reference standard,
trials must have specified that patients were observed for at least 24 hours. We
used the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) to
evaluate bias and applicability of the included studies. We calculated positive
and negative likelihood ratios (LR+ and LR-) of physical examination ("hard
signs" of vascular injury), US, and ABI. Using established CTA test
characteristics (sensitivity = 96.2%, specificity = 99.2%) and applying the
Pauker-Kassirer method, we developed a test-treatment threshold model (testing
threshold = 0.14%, treatment threshold = 72.9%). RESULTS: We included eight
studies (n = 2,161, arterial injury prevalence = 15.5%). Studies had variable
quality with most at high risk for partial and double verification bias. Some
studies investigated multiple index tests: physical examination (hard signs) in
three studies (n = 1,170), ABI in five studies (n = 1,040), and US in four
studies (n = 173). Due to high heterogeneity (I2 > 75%) of the results, we could
not calculate LR+ or LR- for hard signs or LR+ for ABI. The weighted prevalence
of arterial injury for ABI was 14.3% and LR- was 0.59 (95% confidence interval
[CI] = 0.48-0.71) resulting in a posttest probability of 9% for arterial injury.
Ultrasonography had weighted prevalence of 18.9%, LR+ of 35.4 (95% CI = 8.3-151),
and LR- of 0.24 (95% CI = 0.08-0.72); posttest probabilities for arterial injury
were 89% and 5% after positive or negative US, respectively. The posttest
probability of arterial injury with positive US (89%) exceeded the CTA treatment
threshold (72.9%). The posttest probabilities of arterial injury with negative US
(5%) and normal ABI (9%) exceeded the CTA testing threshold (0.14%). Normal
examination (no hard or soft signs) with normal ABI in combination had LR- of
0.01 (95% CI = 0.0-0.10) resulting in an arterial injury posttest probability of
0%. CONCLUSIONS: In PET patients, positive US may obviate CTA. In patients with a
normal examination (no hard or soft signs) and a normal ABI, arterial injury can
be ruled out. However, a normal ABI or negative US cannot independently exclude
arterial injury. Due to high study heterogeneity, we cannot make recommendations
when hard signs are present or absent or when ABI is abnormal. In these
situations, one should use clinical judgment to determine the need for further
observation, CTA or catheter angiography, or surgical exploration.
PMID- 28493615
TI - Why we need fairer allocation rules for patients with hepatocellular carcinoma
awaiting a liver transplant?
PMID- 28493616
TI - Impact of a webcast on nurses' delivery of tobacco dependence treatment.
AB - AIMS AND OBJECTIVES: To evaluate an educational programme about nurses' role in
tobacco dependence treatment, and its webcast component, on the long-term impact
of increasing the frequency of nurses' self-reported changes in practice related
to delivery of smoking cessation interventions. BACKGROUND: Healthcare
professionals' knowledge about evidence-based tobacco dependence treatment using
the 5As framework (Ask about tobacco use, Advise users to quit, Assess
willingness to quit, Assist in making a quit plan and Arrange for follow-up,
including referral to a quitline) is essential to increase smoking cessation
rates in the United States. DESIGN: A 6-month pre-post design. METHODS: A
convenience sample of nurses (N = 283) from Kentucky and Louisiana was provided
access to the webcast and printed toolkit. Responses from those who completed an
online survey at baseline, and at 3 or 6 months postimplementation of the
educational programme were included in an analysis of changes in the consistent
(always/usually) delivery of the 5As plus referral to the quitline. RESULTS:
After 3 months, the intervention had a significant impact on increasing nurses'
reports of consistently providing the 5As to patients who smoked, which was
largely sustained at 6 months. Nurses who viewed the webcast were three times
more likely to refer smokers to a quitline at 3 months; and four times more
likely at 6 months than those who did not. CONCLUSIONS: An online educational
programme, plus printed toolkit about tobacco dependence treatment increased
nurses' delivery of smoking cessation interventions over time. This study
provided preliminary evidence that including a webcast in a nurse-targeted
educational programme could significantly increase the proportion of nurses who
referred smokers to a quitline beyond the benefit of access to printed materials
and web-based resources. RELEVANCE TO CLINICAL PRACTICE: Distance learning is a
feasible mechanism for enhancing nurses' involvement in tobacco dependence
treatment and promoting evidence-based clinical practice.
PMID- 28493617
TI - Anti-inflammatory bioactive equivalence of combinatorial components beta
carboline alkaloids identified in Arenaria kansuensis by two-dimensional
chromatography and solid-phase extraction coupled with liquid-liquid extraction
enrichment technology.
AB - Bioactive equivalent combinatorial components play a critical role in herbal
medicines. However, how to discover and enrich them efficiently is a question for
herbal pharmaceuticals researchers. In our work, a novel two-dimensional reversed
phase/hydrophilic interaction high-performance liquid chromatography method was
established to perform real-time components trapping and combining for
preparation and isolation of coeluting components. Arenaria kansuensis was taken
as an example, and solid-phase extraction coupled with liquid-liquid extraction
as a simple and efficient method for enriching trace components, reversed phase
column coupled with hydrophilic interaction liquid chromatography XAmide column
as two-dimensional chromatography technology for isolation and preparation of
coeluting constituents, enzyme-linked immune-sorbent assay as bio-guided assay,
and anti-inflammatory bioactivity evaluation for bioactive constituents. A
combination of 12 beta-carboline alkaloids was identified as anti-inflammatory
bioactive equivalent combinatorial components from A. kansuensis, which accounts
for 1.9% w/w of original A. kansuensis. This work answers the key question of
which are real anti-inflammatory components from A. kansuensis and provides a
fast and efficient approach for discovering and enriching trace beta-carboline
alkaloids from herbal medicines for the first time. More importantly, the
discovery of bioactive equivalent combinatorial components could improve the
quality control of herbal products and inspire a herbal medicine based on
combinatorial therapeutics.
PMID- 28493618
TI - Pondering practice: Enhancing the art of reflection.
AB - AIMS AND OBJECTIVES: The aim of this study was to describe the effect that
immersive simulation experiences and guided reflection can have on the
undergraduate nurses' understanding of how stressful environments impact their
emotions, performance and ability to implement safe administration of
medications. BACKGROUND: Patient safety can be jeopardised if nurses are unsure
of how to appropriately manage and respond to interruptions. Medication
administration errors are a major patient safety issue and often occur as a
consequence of ineffective interruption management. The skills associated with
medication administration are most often taught to, and performed by,
undergraduate nurses in a controlled environment. However, the clinical
environment in which nurses are expected to administer medications is often
highly stressed and nurses are frequently interrupted. DESIGN/METHODS: This study
used role-play simulation and written reflections to facilitate deeper levels of
student self-awareness. A qualitative approach was taken to explore students'
understanding of the effects of interruptions on their ability to undertake safe
medication administration. Convenience sampling of second-year undergraduate
nursing students enrolled in a medical-surgical subject was used in this study.
Data were obtained from 451:528 (85.42%) of those students and analysed using
thematic analysis. RESULTS: Students reported increasing consciousness and the
importance of reflection for evaluating performance and gaining self-awareness.
They described self-awareness, effective communication, compassion and empathy as
significant factors in facilitating self-efficacy and improved patient care
outcomes. CONCLUSIONS: Following a role-play simulation experience, student
nurses reported new knowledge and skill acquisition related to patient safety,
and new awareness of the need for empathetic and compassionate care during
medication administration. Practicing medication administration in realistic
settings adds to current strategies that aim to reduce medication errors by
allowing students to reflect on and in practice and develop strategies to ensure
patient safety. RELEVANCE TO CLINICAL PRACTICE: Experiencing clinical scenarios
within the safety of simulated environments, offers undergraduate student nurses
an opportunity to reflect on practice to provide safer, more empathetic and
compassionate care for patients in the future.
PMID- 28493619
TI - Access to Hexahydrocarbazoles: The Thorpe-Ingold Effects of the Ligand on
Enantioselectivity.
AB - A novel cyclization reaction of methylenemalonate with indoles is reported, and
it provides efficient access to a variety of hexahydrocarbazoles. The
enantioselective version was realized by a finely tuned ligand/CuII catalyst. The
optically active hexahydrocarbazoles contain three quaternary carbon centers and
are obtained in up to 99 % yield with greater than 99:1 d.r. and up to greater
than 99 % ee. This reaction can be carried out on gram scale and stereoselective
transformation of the product led to the core structure of a series of alkaloids
from Kopsia plants.
PMID- 28493621
TI - Substituent Effects in Parallel-Displaced pi-pi Stacking Interactions: Distance
Matters.
AB - Host-guest systems with Rebek imide type receptors and a 2,6
di(isobutyramido)pyridine ligand were employed to investigate substituent effects
in parallel-displaced pi-pi stacking interactions. Changing the intermolecular
distance between the para substituent on the aromatic platform of the receptor
and the pyridine ring of the guest results in a strongly different substituent
effect. With a short ethyne-1,2-diyl spacer between the Rebek imide and the
aromatic platform, partial overlap of substituent and guest stabilizes the pi-pi
stacking interactions independent of the electronic nature of the substituent
(Wheeler-Houk model). When the substituent is shifted further away by using a
buta-1,3-diyne-1,4-diyl spacer, direct, through-space interactions between
substituent and guest are prevented. A linear correlation between logKa (Ka
=association constant) and the Hammett substituent constant sigmapara is
observed, confirming predictions by the Hunter-Sanders model experimentally.
PMID- 28493620
TI - Engineering a Small HOMO-LUMO Gap and Intramolecular C-H Borylation by
Diborene/Anthracene Orbital Intercalation.
AB - The diborene 1 was synthesized by reduction of a mixture of 1,2-di-9-anthryl-1,2
dibromodiborane(4) (6) and trimethylphosphine with potassium graphite. The X-ray
structure of 1 shows the two anthryl rings to be parallel and their pi(C14 )
systems perpendicular to the diborene pi(B=B) system. This twisted conformation
allows for intercalation of the relatively high-lying pi(B=B) orbital and the low
lying pi* orbital of the anthryl moiety with no significant conjugation,
resulting in a small HOMO-LUMO gap (HLG) and ultimately a C-H borylation of the
anthryl unit. The HLG of 1 was estimated to be 1.57 eV from the onset of the long
wavelength band in its UV/Vis absorption spectrum (THF, lambdaonset =788 nm). The
oxidation of 1 with elemental selenium afforded diboraselenirane 8 in
quantitative yield. By oxidative abstraction of one phosphine ligand by another
equivalent of elemental selenium, the B-B and C1 -H bonds of 8 were cleaved to
give the cyclic 1,9-diborylanthracene 9.
PMID- 28493622
TI - IUAPC 2017 Distinguished Women in Chemistry or Chemical Engineering.
PMID- 28493624
TI - The effect of acute exercise on blood concentrations of brain-derived
neurotrophic factor in healthy adults: a meta-analysis.
AB - It has been hypothesized that one mechanism through which physical activity
provides benefits to cognition and mood is via increasing brain-derived
neurotrophic factor (BDNF) concentrations. Some studies have reported immediate
benefits to mood and various cognitive domains after a single session of
exercise. This meta-analysis sought to determine the effect of a single exercise
session on concentrations of BDNF in peripheral blood, in order to evaluate the
potential role of BDNF in mediating the beneficial effects of exercise on brain
health. MEDLINE, Embase, PsycINFO, SPORTDiscus, Rehabilitation & Sports Medicine
Source, and CINAHL databases were searched for original, peer-reviewed reports of
peripheral blood BDNF concentrations before and after acute exercise
interventions. Risk of bias within studies was assessed using standardized
criteria. Standardized mean differences (SMDs) were generated from random effects
models. Risk of publication bias was assessed using a funnel plot and Egger's
test. Potential sources of heterogeneity were explored in subgroup analyses. In
55 studies that met inclusion criteria, concentrations of peripheral blood BDNF
were higher after exercise (SMD = 0.59, 95% CI: 0.46-0.72, P < 0.001). In meta
regression analysis, greater duration of exercise was associated with greater
increases in BDNF. Subgroup analyses revealed an effect in males but not in
females, and a greater BDNF increase in plasma than serum. Acute exercise
increased BDNF concentrations in the peripheral blood of healthy adults. This
effect was influenced by exercise duration and may be different across genders.
PMID- 28493625
TI - Significant OH production under surface cleaning and air cleaning conditions:
Impact on indoor air quality.
AB - We report measurements of hydroxyl (OH) and hydroperoxy (HO2 ) radicals made by
laser-induced fluorescence spectroscopy in a computer classroom (i) in the
absence of indoor activities (ii) during desk cleaning with a limonene-containing
cleaner (iii) during operation of a commercially available "air cleaning" device.
In the unmanipulated environment, the one-minute averaged OH concentration
remained close to or below the limit of detection (6.5*105 molecule cm-3 ),
whilst that of HO2 was 1.3*107 molecule cm-3 . These concentrations increased to
~4*106 and 4*108 molecule cm-3 , respectively during desk cleaning. During
operation of the air cleaning device, OH and HO2 concentrations reached ~2*107
and ~6*108 molecule cm-3 respectively. The potential of these OH concentrations
to initiate chemical processing is explored using a detailed chemical model for
indoor air (the INDCM). The model can reproduce the measured OH and HO2
concentrations to within 50% and often within a few % and demonstrates that the
resulting secondary chemistry varies with the cleaning activity. Whilst terpene
reaction products dominate the product composition following surface cleaning,
those from aromatics and other VOCs are much more important during the use of the
air cleaning device.
PMID- 28493623
TI - Aripiprazole Suppression of Drinking in a Clinical Laboratory Paradigm: Influence
of Impulsivity and Self-Control.
AB - BACKGROUND: Aspects of impulsivity have been implicated in the development, or
maintenance, of alcohol use disorder (AUD). The brain dopamine system is
implicated in both reward processing/memory (typically subcortical) and in brain
inhibitory control mechanisms (typically cortical). Using a validated clinical
laboratory paradigm, the dopamine/serotonin "stabilizing" drug, aripiprazole was
evaluated in non-treatment-seeking AUD individuals based on their level of
impulsivity/self-control. METHODS: Ninety-nine individuals (77% male; mean age
27; 7.5 drinks per day; 83% heavy drinking days) meeting DSM-IV criteria for
alcohol dependence were randomized to aripiprazole (N = 47 evaluable) or placebo
(N = 48 evaluable) based on their Barratt Impulsiveness Scale (BIS-11) score
(above or below 68). Aripiprazole, or similar placebo, was titrated to 15 mg over
8 days. Drinking was recorded over 6 days under natural conditions. On Day 8,
after 1 day of required abstinence, individuals participated in a bar laboratory
paradigm that included a priming drink (breath alcohol concentration [BAC] target
0.02 to 0.03 g/dl) and free-choice consumption of up to 8 drinks (max BAC 0.1
g/dl) in exchange for a "bar credit" of $2 per drink (max $16). End points were
drinks per day under natural conditions and drinks consumed in the bar laboratory
after the priming drink. RESULTS: There was no significant main effect of
aripiprazole or interaction with BIS-11 score during the natural drinking period.
However, there was a main effect of aripiprazole on bar laboratory drinking (p =
0.04) and aripiprazole reduced the total number of drinks consumed more among
individuals with low self-control (p = 0.034) and increased latency to consume
those drinks (p = 0.045) more among those with high impulsivity. Relative to
placebo, aripiprazole caused more side effects and increased alcohol-induced
sedation, but neither significantly influenced its interaction with
impulsivity/self-control scores on drinking. CONCLUSIONS: This paradigm forced a
choice between immediate drinking reward and delayed monetary reward. In those
with high impulsivity and/or low self-control, aripiprazole shifts the balance
away from immediate drinking toward a later reward. Medications targeting
cortical dopamine/serotonin balance might show clinical benefit of reduced
drinking, among individuals with impulsivity/low self-control.
PMID- 28493626
TI - Why Do People Choose Emergency and Urgent Care Services? A Rapid Review Utilizing
a Systematic Literature Search and Narrative Synthesis.
AB - OBJECTIVES: Rising demand for emergency and urgent care services is well
documented, as are the consequences, for example, emergency department (ED)
crowding, increased costs, pressure on services, and waiting times. Multiple
factors have been suggested to explain why demand is increasing, including an
aging population, rising number of people with multiple chronic conditions, and
behavioral changes relating to how people choose to access health services. The
aim of this systematic mapping review was to bring together published research
from urgent and emergency care settings to identify drivers that underpin patient
decisions to access urgent and emergency care. METHODS: Systematic searches were
conducted across Medline (via Ovid SP), EMBASE (via Ovid), The Cochrane Library
(via Wiley Online Library), Web of Science (via the Web of Knowledge), and the
Cumulative Index to Nursing and Allied Health Literature (CINAHL; via EBSCOhost).
Peer-reviewed studies written in English that reported reasons for accessing or
choosing emergency or urgent care services and were published between 1995 and
2016 were included. Data were extracted and reasons for choosing emergency and
urgent care were identified and mapped. Thematic analysis was used to identify
themes and findings were reported qualitatively using framework-based narrative
synthesis. RESULTS: Thirty-eight studies were identified that met the inclusion
criteria. Most studies were set in the United Kingdom (39.4%) or the United
States (34.2%) and reported results relating to ED (68.4%). Thirty-nine percent
of studies utilized qualitative or mixed research designs. Our thematic analysis
identified six broad themes that summarized reasons why patients chose to access
ED or urgent care. These were access to and confidence in primary care; perceived
urgency, anxiety, and the value of reassurance from emergency-based services;
views of family, friends, or healthcare professionals; convenience (location, not
having to make appointment, and opening hours); individual patient factors (e.g.,
cost); and perceived need for emergency medical services or hospital care,
treatment, or investigations. CONCLUSIONS: We identified six distinct reasons
explaining why patients choose to access emergency and urgent care services:
limited access to or confidence in primary care; patient perceived urgency;
convenience; views of family, friends, or other health professionals; and a
belief that their condition required the resources and facilities offered by a
particular healthcare provider. There is a need to examine demand from a whole
system perspective to gain better understanding of demand for different parts of
the emergency and urgent care system and the characteristics of patients within
each sector.
PMID- 28493627
TI - Oxidative-Insertion Reactivity Across a Geometrically Constrained Metal->Borane
Interaction.
AB - While interest in cooperative reactivity of transition metals and Lewis acids is
receiving significant attention, the scope of known reactions that directly
exploit the polarized reverse-dative sigma-bond of metal-borane complexes (i.e.,
M->BR3 ) remains limited. Described herein is that the platinum
(boryl)iminomethane (BIM) complex [Pt(kappa2 -N,B-Cy2 BIM)(CNArDipp2 )] can
effect the oxidative insertion of a range of unsaturated organic substrates,
including azides, isocyantes, and nitriles, as well as CO2 and elemental sulfur
(S8 ). In addition, alkyl migration processes available to the BIM framework
allow for post-insertion reaction sequences resulting in product release from the
metal center.
PMID- 28493628
TI - The confidence of undergraduate dental students when carrying out prosthodontic
treatment and their perception of the quality of prosthodontic education.
AB - INTRODUCTION: Despite the falling number of edentulous patients within the UK,
there is still a large demand for the provision of removable prostheses. On
qualification, dentists should have the knowledge and skills to provide these
prostheses, but previous studies have shown that final-year dental undergraduate
confidence in treating denture patients is lacking. AIM: To explore undergraduate
dental student confidence whilst carrying out prosthodontic treatment, and to
explore their perceptions of the quality of their prosthodontic education.
METHOD: An anonymous questionnaire was distributed to all (n=203) dental
undergraduates in Years 3 to 5 at the University of Bristol. The questionnaire
utilised a range of data collection methods including confidence interval ranked
responses and qualitative measures. The data were analysed using SPSS. RESULTS:
The response rate was 51%. Undergraduate perception of confidence increased
throughout the years of study (P<.001). There was also an increase in the number
of partial and complete denture cases treated as students progressed through the
course (P<.001). Overall, students were satisfied with their prosthodontic
teaching, although students thought that too much time was allocated to
laboratory teaching, and that increasing their clinical experience would be most
beneficial in increasing their confidence levels. CONCLUSION: Student confidence
in carrying out prosthetic treatment increased as students progressed through the
course, and confidence levels would be increased further with increased clinical
experience.
PMID- 28493629
TI - It is the time to rethink the criteria to define transplantable kidneys. Should
we combine histological and clinical evaluation?
PMID- 28493630
TI - Clinical outcomes of ABO- and HLA-incompatible kidney transplantation: a
nationwide cohort study.
AB - This was a nationwide cohort study to investigate the impact of anti-A/B and
donor-specific anti-HLA (HLA-DSA) antibodies on the clinical outcomes in kidney
transplant recipients (KTRs). We classified a total of 1964 KTRs into four
groups: transplants from ABO-incompatible donors (ABOi, n = 248); transplants in
recipients with HLA-DSA (HLAi, n = 144); transplants from combined ABOi and HLAi
donors (ABOi + HLAi, n = 31); and a control group for whom neither ABOi nor HLAi
was applicable (CONT, n = 1541). We compared the incidence of biopsy-proven acute
rejection (BPAR), allograft and patient survival rates. The incidence of BPAR was
higher in the HLAi and ABOi + HLAi groups relative to the CONT group; in
contrast, it was not higher in the ABOi group. Death-censored graft survival
rates did not differ across the four groups. However, relative to the CONT group,
patient survival rate was reduced in the ABOi and ABOi + HLAi groups, and with
infection being the most common cause of death. Further, multivariable analysis
revealed that desensitization therapy because of ABOi or HLAi was independent
risk factors for patient mortality. HLAi was a more important risk factor for
BPAR compared with ABOi. However, pretransplant desensitization therapy for
either ABOi or HLAi significantly increased the risk of infection-related
mortality.
PMID- 28493632
TI - Dangerously mixed.
PMID- 28493633
TI - Capturing the Role of Explicit Solvent in the Dimerization of RuV (bda) Water
Oxidation Catalysts.
AB - A ground-breaking empirical valence bond study for a soluble transition-metal
complex is presented. The full reaction of catalyst monomers approaching and
reacting in the RuV oxidation state were studied. Analysis of the solvation shell
in the reactant and along the reaction coordinate revealed that the oxo itself is
hydrophobic, which adds a significant driving force to form the dimer. The effect
of the solvent on the reaction between the prereactive dimer and the product was
small. The solvent seems to lower the barrier for the isoquinoline (isoq) complex
while it is increased for pyridines. By comparing the reaction in the gas phase
and solution, the proposed pi-stacking interaction of the isoq ligands is found
to be entirely driven by the water medium.
PMID- 28493631
TI - Allergen immunotherapy for allergic rhinoconjunctivitis: A systematic review and
meta-analysis.
AB - BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in
the process of developing Guidelines on Allergen Immunotherapy (AIT) for Allergic
Rhinoconjunctivitis. To inform the development of clinical recommendations, we
undertook a systematic review to assess the effectiveness, cost-effectiveness,
and safety of AIT in the management of allergic rhinoconjunctivitis. METHODS: We
searched nine international biomedical databases for published, in-progress, and
unpublished evidence. Studies were independently screened by two reviewers
against predefined eligibility criteria and critically appraised using
established instruments. Our primary outcomes of interest were symptom,
medication, and combined symptom and medication scores. Secondary outcomes of
interest included cost-effectiveness and safety. Data were descriptively
summarized and then quantitatively synthesized using random-effects meta
analyses. RESULTS: We identified 5960 studies of which 160 studies satisfied our
eligibility criteria. There was a substantial body of evidence demonstrating
significant reductions in standardized mean differences (SMD) of symptom (SMD
0.53, 95% CI -0.63, -0.42), medication (SMD -0.37, 95% CI -0.49, -0.26), and
combined symptom and medication (SMD -0.49, 95% CI -0.69, -0.30) scores while on
treatment that were robust to prespecified sensitivity analyses. There was in
comparison a more modest body of evidence on effectiveness post-discontinuation
of AIT, suggesting a benefit in relation to symptom scores. CONCLUSIONS: AIT is
effective in improving symptom, medication, and combined symptom and medication
scores in patients with allergic rhinoconjunctivitis while on treatment, and
there is some evidence suggesting that these benefits are maintained in relation
to symptom scores after discontinuation of therapy.
PMID- 28493634
TI - An experimental study of the recovery of injured porcine lungs with prolonged
normothermic cellular ex vivo lung perfusion following donation after circulatory
death.
AB - Donation after circulatory death (DCD) is an underused source of donor lungs.
Normothermic cellular ex vivo lung perfusion (EVLP) is effective in preserving
standard donor lungs but may also be useful in the preservation and assessment of
DCD lungs. Using a model of DCD and prolonged EVLP, the effects of donor warm
ischemia and postmortem ventilation on graft recovery were evaluated. Adult male
swine underwent general anesthesia and heparinization. In the control group (n =
4), cardioplegic arrest was induced and the lungs were procured immediately. In
the four treatment groups, a period of agonal hypoxia was followed by either 1 h
of warm ischemia with (n = 4) or without (n = 4) ventilation or 2 h of warm
ischemia with (n = 4) or without (n = 4) ventilation. All lungs were studied on
an EVLP platform for 24 h. Hemodynamic measures, compliance, and oxygenation on
EVLP were worse in all DCD lungs compared with controls. Hemodynamics and
compliance normalized in all lungs after 24 h of EVLP, but DCD lungs demonstrated
impaired oxygenation. Normothermic cellular EVLP is effective in preserving and
monitoring of DCD lungs. Early donor postmortem ventilation and timely
procurement lead to improved graft function.
PMID- 28493635
TI - The double-edged experience of healthcare encounters among women with
endometriosis: A qualitative study.
AB - AIMS AND OBJECTIVES: To identify and describe the experience of healthcare
encounters among women with endometriosis. BACKGROUND: Endometriosis is a
"hidden" chronic gynaecological disease appearing in every 10th woman of fertile
age. Different manifestations of pain are the main symptoms, often leading to
impaired physical and mental health, and lower quality of life. Previous research
on healthcare experiences among women with endometriosis has focused on
diagnostic delay and experiences of encountering general practitioners. DESIGN: A
qualitative, interpretive, phenomenological approach was used. METHODS: We
interviewed nine women aged 23-55, with a laparoscopy-confirmed diagnosis of
endometriosis. The interviews were recorded and transcribed verbatim. The data
were analysed following the steps of the interpretive phenomenological approach.
RESULTS: Two themes were identified in the interview transcripts: being treated
with ignorance and being acknowledged. The essence: "the double-edged experience
of healthcare encounters" emerged from the themes. The women's experience was
double-edged as it involved contradictory feelings: the encounters were
experienced as both destructive or constructive. On the one hand, the destructive
side was characterised by ignorance, exposure and disbelief. On the other hand,
the constructive side made the women feel acknowledged and confirmed, boosting
their self-esteem. CONCLUSIONS: The new and important aspects of the findings are
that the experience of healthcare encounters is for the first time expressed as
double-edged: both destructive and constructive. The experience was of specific
importance as it affected the women's perceptions of themselves and of their
bodies. RELEVANCE TO CLINICAL PRACTICE: The information about the constructive
side of the experience is of clinical valuable for all healthcare professionals
(nurses, midwives and doctors) encountering these women, as it provides a new
level of understanding of the experiences. The findings demonstrate both
psychological and practical aspects that can help professionals to improve the
encounters.
PMID- 28493636
TI - Families' perceptions of the contribution of intellectual disability clinical
nurse specialists in Ireland.
AB - AIM AND OBJECTIVES: To explore families' perceptions of the contribution of
clinical nurse specialists in intellectual disability nursing in Ireland.
BACKGROUND: Clinical nurse specialists roles have developed over the years and
are seen as complex and multifaceted, causing confusion, frustration and
controversy. 2001 saw the formal introduction of clinical nurse specialists roles
in Ireland across nursing including intellectual disability. DESIGN: A
exploratory qualitative approach using semistructured one-to-one interviews with
10 family members regarding their perceptions of the clinical nurse specialists
in intellectual disability. METHODS: Data were audio-recorded, transcribed and
analysed using Burnard's framework. Ethical approval was gained and access
granted by service providers. FINDINGS: The study highlights that intellectual
disability clinical nurse specialists contribute and support care deliver across
a range of areas, including personal caring, supporting and empowering families,
liaison, education and leadership. CONCLUSIONS: Clinical nurse specialists have
an important role and contribution in supporting families and clients, and
Ireland is in a unique position to develop knowledge regarding specialist care
for people with intellectual disability that can be shared nationally and
internationally. RELEVANCE TO CLINICAL PRACTICE: Ireland is in a unique position
to develop knowledge regarding specialist care for people with intellectual
disability that can be shared and adapted by other healthcare professionals in
other countries that do not have a specialised intellectual disability nurses.
PMID- 28493637
TI - Single-Molecule Photoactivation FRET: A General and Easy-To-Implement Approach To
Break the Concentration Barrier.
AB - Single-molecule fluorescence resonance energy transfer (sm-FRET) has become a
widely used tool to reveal dynamic processes and molecule mechanisms hidden under
ensemble measurements. However, the upper limit of fluorescent species used in sm
FRET is still orders of magnitude lower than the association affinity of many
biological processes under physiological conditions. Herein, we introduce single
molecule photoactivation FRET (sm-PAFRET), a general approach to break the
concentration barrier by using photoactivatable fluorophores as donors. We
demonstrate sm-PAFRET by capturing transient FRET states and revealing new
reaction pathways during translation using MUm fluorophore labeled species, which
is 2-3 orders of magnitude higher than commonly used in sm-FRET measurements. sm
PAFRET serves as an easy-to-implement tool to lift the concentration barrier and
discover new molecular dynamic processes and mechanisms under physiological
concentrations.
PMID- 28493638
TI - Chemically Controlled Spatiotemporal Oscillations of Colloidal Assemblies.
AB - We report an autonomous oscillatory micromotor system in which active colloidal
particles form clusters, the size of which changes periodically. The system
consists of an aqueous suspension of silver orthophosphate microparticles under
UV illumination, in the presence of varying concentrations of hydrogen peroxide.
The colloid particles first attract each other to form clusters. After a short
delay, these clusters abruptly disperse and oscillation begins, alternating
between clustering and dispersion of particles. After a cluster oscillation
initiates, the oscillatory wave propagates to nearby clusters and eventually all
the clusters oscillate in phase-shifted synchrony. The oscillatory behavior is
governed by an electrolytic self-diffusiophoretic mechanism which involves
alternating electric fields generated by the competing reduction and oxidation of
silver. The oscillation frequency is tuned by changing the concentration of
hydrogen peroxide. The addition of inert silica particles to the system results
in hierarchical sorting and packing of clusters. Densely packed Ag3 PO4 particles
form a non-oscillating core with an oscillating shell composed largely of silica
microparticles.
PMID- 28493639
TI - Achiral Pyridine Ligand-Enabled Enantioselective Radical Oxytrifluoromethylation
of Alkenes with Alcohols.
AB - A conceptually novel strategy with achiral pyridine as the ancillary ligand to
stabilize high-valent copper species for the first asymmetric radical
oxytrifluoromethylation of alkenes with alcohols under CuI /phosphoric acid dual
catalysis has been developed. The transformation features mild reaction
conditions, a remarkably broad substrate scope and excellent functional group
tolerance, offering an efficient approach to a wide range of trifluoromethyl
substituted tetrahydrofurans bearing an alpha-tertiary stereocenter with
excellent enantioselectivity. Mechanistic studies support the presumed role of
the achiral pyridine as a coordinative ligand on copper metal to stabilize the
key transient reaction species involved in the asymmetric induction process.
PMID- 28493640
TI - Synthesis of Dibenzo[hi,st]ovalene and Its Amplified Spontaneous Emission in a
Polystyrene Matrix.
AB - A large number of graphene molecules, or large polycyclic aromatic hydrocarbons
(PAHs), have been synthesized and display various optoelectronic properties.
Nevertheless, their potential for application in photonics has remained largely
unexplored. Herein, we describe the synthesis of a highly luminescent and stable
graphene molecule, namely a substituted dibenzo[hi,st]ovalene (DBO 1), with
zigzag edges and elucidate its promising optical-gain properties by means of
ultrafast transient absorption spectroscopy. Upon incorporation of DBO into an
inert polystyrene matrix, amplified stimulated emission can be observed with a
relatively low power threshold (ca. 60 MUJ cm-2 ), thus highlighting its high
potential for lasing applications.
PMID- 28493641
TI - Impact of pre-existing or new-onset atrial fibrillation on 30-day clinical
outcomes following transcatheter aortic valve replacement: Results from the BRAVO
3 randomized trial.
AB - BACKGROUND: Prior studies have suggested that patients with atrial fibrillation
(AF) undergoing transcatheter aortic valve replacement (TAVR) are at higher risk
for adverse cardiovascular events. Whether procedural bivalirudin compared with
unfractionated heparin (UFH) has a beneficial effect on early outcomes in these
patients is unknown. We examined for the effect of baseline or new-onset AF
within 30 days of TAVR and explored for the effect of bivalirudin versus UFH by
AF status, on 30-day outcomes from the BRAVO 3 trial. METHODS: The BRAVO-3 trial
multicenter randomized trial included 802 patients undergoing transfemoral TAVR
randomized to bivalirudin or UFH. We compared AF and no-AF groups and examined
for 30-day Bleeding Academic Research Consortium type >=3b bleeding, major
vascular complications and all ischemic endpoints. Adjusted outcomes were
analyzed using logistic regression methods. RESULTS: Of the study population,
41.4% (n = 332) patients had baseline or new-onset AF within 30 days of TAVR,
whereas 58.6% (n = 470) had no AF. Patients with AF had greater prevalence of
renal dysfunction, lower left ventricular ejection fraction, and higher euroSCORE
I compared with their counterparts without AF. Among AF and no-AF patients, there
were no significant baseline differences between bivalirudin and UFH groups. At
30 days the incidence of death (6.0 vs. 4.5%, P = 0.324) and stroke (3.9 vs.
2.6%, P = 0.274) was similar in AF vs. no-AF patients. However, new-onset AF (n =
38) was associated with significantly greater crude risk of 30-day stroke
compared with no AF (HR 4.49, 95% CI 1.37-14.67). Regardless of AF status, there
were no differences in 30-day death (P-int = 0.652) or stroke (P-int = 0.066) by
anticoagulation type. CONCLUSIONS: Prior or new-onset AF is noted in more than
one-third of patients undergoing transfemoral TAVR. Despite greater baseline
comorbidities than non-AF patients, AF was not associated with significantly
higher risk of adjusted 30-day outcomes. In the BRAVO 3 trial, early outcomes
were similar regardless of anticoagulant strategy in each group.
PMID- 28493644
TI - The quality of life of people who have chronic wounds and who self-treat.
AB - AIMS AND OBJECTIVES: The aim of this study was to investigate the effect of
chronic wounds on the physical, emotional, social, lifestyle and financial
domains of quality of life among people who self-treat their wounds. BACKGROUND:
Patient-centred models of care have received increased attention over recent
decades because of the potential to contribute positively to the patient's health
and well-being. A contemporary understanding of the effect of chronic wounds on
quality of life may assist care providers and healthcare systems to respond to
patient needs and improve patient outcomes. METHOD: A qualitative, exploratory
study was conducted in Victoria, Australia. Participants were aged 18 years or
older and had a chronic wound that was currently or previously self-treated. A
sample of 25 participants was recruited from the community, and in-depth
interviews were conducted in participants' homes. A thematic analysis was
conducted to identify themes that represented the physical, emotional, social,
lifestyle and financial domains of quality of life. RESULTS: Study participants
(n = 25) were 71 years of age (average), and the majority had a leg wound.
Participants experienced a negative effect on quality of life. Physical
limitations affected activity and compromised the management of other health
conditions. Participants felt frustrated with and distrusting of healthcare
professionals from whom they received advice and care. Daily lifestyle and
workforce participation were disrupted when receiving professional care. Wound
treatment and professional care expenses negatively affected personal finances.
CONCLUSION: Continued effort is required to develop relationships and treatment
regimens that are conducive to healing and to optimise well-being. Additionally,
healthcare systems should identify and address structural shortcomings of care
services to create more patient-centred models of wound care in the community
setting.
PMID- 28493642
TI - Adverse Events With Ketamine Versus Ketofol for Procedural Sedation on Adults: A
Double-blind, Randomized Controlled Trial.
AB - OBJECTIVES: The goal of our study was to compare the frequency and severity of
recovery reactions between ketamine and ketamine-propofol 1:1 admixture
("ketofol"). METHODS: We performed a multicentric, randomized, double-blind trial
in which adult patients received emergency procedural sedations with ketamine or
ketofol. Our primary outcome was the proportion of unpleasant recovery reactions.
Other outcomes were frequency of interventions required by these recovery
reactions, rates of respiratory or hemodynamic events, emesis, and satisfaction
of patients as well as providers. RESULTS: A total of 152 patients completed the
study, 76 in each arm. Compared with ketamine, ketofol determined a 22% reduction
in recovery reactions incidence (p < 0.01) and less clinical and pharmacologic
interventions required by these reactions. There was no serious adverse event in
both groups. Rates in hemodynamic or respiratory events as well as satisfaction
scores were similar. Significantly fewer patients experienced emesis with
ketofol, with a threefold reduction in incidence compared with ketamine.
CONCLUSION: We found a significant reduction in recovery reactions and emesis
frequencies among adult patients receiving emergency procedural sedations with
ketofol, compared with ketamine.
PMID- 28493645
TI - Carbon-Fluorine Reductive Elimination from Nickel(III) Complexes.
AB - We report a C-F reductive elimination from a characterized first-row aryl metal
fluoride complex. Reductive elimination from the presented nickel(III) complexes
is faster than C-F bond formation from any other characterized aryl metal
fluoride complex.
PMID- 28493646
TI - Validation of the No Objective Testing Rule and Comparison to the HEART Pathway.
AB - BACKGROUND: The no objective testing rule (NOTR) is a decision aid designed to
safely identify emergency department (ED) patients with chest pain who do not
require objective testing for coronary artery disease. OBJECTIVES: The objective
was to validate the NOTR in a cohort of U.S. ED patients with acute chest pain
and compare its performance to the HEART Pathway. METHODS: A secondary analysis
of 282 participants enrolled in the HEART Pathway randomized controlled trial was
conducted. Each patient was classified as low risk or at risk by the NOTR.
Sensitivity for major adverse cardiac events (MACE) at 30 days was calculated in
the entire study population. NOTR and HEART Pathways were compared among patients
randomized to the HEART Pathway in the parent trial using McNemar's test and the
net reclassification improvement (NRI). RESULTS: Major adverse cardiac events
occurred in 22/282 (7.8%) participants, including no deaths, 16/282 (5.6%) with
myocardial infarction (MI), and 6/282 (2.1%) with coronary revascularization
without MI. NOTR was 100% (95% confidence interval [CI] = 84.6%-100%) sensitive
for MACE and identified 78/282 patients (27.7%, 95% = CI 22.5-33.3%) as low risk.
In the HEART Pathway arm (n = 141), both NOTR and HEART Pathway identified all
patients with MACE as at risk. Compared to NOTR, the HEART Pathway was able to
correctly reclassify 27 patients without MACE as low risk, yielding a NRI of
20.8% (95% CI = 11.3%-30.2%). CONCLUSIONS: Within a U.S. cohort of ED patients
with chest pain, the NOTR and HEART Pathway were 100% sensitive for MACE at 30
days. However, the HEART Pathway identified more patients suitable for early
discharge than the NOTR.
PMID- 28493647
TI - The liminality of the patient with dementia in hospital.
AB - AIMS AND OBJECTIVES: The aim was to explore the experiences of people with
dementia in subacute geriatric rehabilitation hospitals to critically evaluate
the care received by such patients. BACKGROUND: Globally, the number of people
with dementia is growing and is expected to impact progressively more on health
systems. People with dementia can become deconditioned and deteriorate in
cognitive function while in hospital. The unfamiliar environment and people can
cause the person to become disorientated, which then leads to behavioural
symptoms which complicate care. DESIGN: Critical ethnography. METHODS: Methods
included observation with field notes and 30 audio-recorded conversational
interviews with patients with dementia in an Australian subacute care setting.
Data were collected in May-December 2014, transcribed verbatim and analysed using
thematic analysis. RESULTS: The central theme identified that patients with
dementia described a liminal experience and felt like outsiders in the hospital
environment. This was supported by the subthemes of not understanding why they
were being kept in hospital, feeling lost in the space, bored, anxious about
discharge plans and lacking intersubjective relationships. Many felt imprisoned
by the locked wards. There was little evidence of nursing care delivered in an
empathetic person-centred way. Nurses were busy and engaged with the patients
only superficially. CONCLUSIONS: People with dementia can have a liminal
experience and feel like outsiders in this environment, which does not cater for
the specific needs of this patient group. It should be acknowledged that people
with dementia require additional resources. A caring nurse-patient relationship
is fundamental to the patient experience. Nurses require further support and
education about dementia in order to deliver quality care to this patient group.
RELEVANCE TO CLINICAL PRACTICE: These findings will influence nurse leaders to
advocate for improved resources for nurses to provide appropriate care for
patients with dementia in subacute geriatric hospitals. The clinical practice of
nurses needs to be supported with education, pyschological and material support
to improve the therapeutic environment for patients with cognitive impairment
resulting from dementia.
PMID- 28493648
TI - Detection of Localized Hepatocellular Amino Acid Kinetics by using Mass
Spectrometry Imaging of Stable Isotopes.
AB - Mass spectrometry imaging (MSI) simultaneously detects and identifies the spatial
distribution of numerous molecules throughout tissues. Currently, MSI is limited
to providing a static and ex vivo snapshot of highly dynamic systems in which
molecules are constantly synthesized and consumed. Herein, we demonstrate an
innovative MSI methodology to study dynamic molecular changes of amino acids
within biological tissues by measuring the dilution and conversion of stable
isotopes in a mouse model. We evaluate the method specifically on hepatocellular
metabolism of the essential amino acid l-phenylalanine, associated with liver
diseases. Crucially, the method reveals the localized dynamics of l-phenylalanine
metabolism, including its in vivo hydroxylation to l-tyrosine and co-localization
with other liver metabolites in a time course of samples from different animals.
This method thus enables the dynamics of localized biochemical synthesis to be
studied directly from biological tissues.
PMID- 28493649
TI - Temperature-Driven Planar Chirality Switching of a Pillar[5]arene-Based Molecular
Universal Joint.
AB - The study of an enantiopure bicyclic pillar[5]arene-based molecular universal
joint (MUJ) by single-crystal X-ray diffraction allowed for the first time the
unequivocal assignment of the absolute configuration of a planar chiral
pillar[5]arene by circular dichroism spectroscopy. Crucially, the absolute
configuration of the MUJ was switched reversibly by temperature, with an
accompanying sign inversion of the anisotropy factor that varied by as much as
0.03, which is the largest value ever reported. Mechanistically, the reversible
chirality switching of the MUJ is driven by the threading/dethreading motion of
the fused ring and hence is dependent on both the size and nature of the ring and
the solvent employed, reflecting the critical balance between the self
complexation of the ring by pillar[5]arene, the solvation to the excluded ring,
and the inclusion of solvent molecules in the cavity.
PMID- 28493650
TI - Pro-survival redox signalling in progesterone-mediated retinal neuroprotection.
AB - Retinitis pigmentosa (RP) is a group of hereditary retinal diseases,
characterised by photoreceptor cell loss. Despite a substantial understanding of
the mechanisms leading to cell death, an effective therapeutic strategy is
sought. Our laboratory has previously demonstrated the neuroprotective properties
of Norgestrel, a progesterone analogue, in the degenerating retina, mediated in
part by the neurotrophic factor basic fibroblast growth factor (bFGF). In other
retinal studies, we have also presented a pro-survival role for reactive oxygen
species (ROS), downstream of bFGF. Thus, we hypothesized that Norgestrel utilises
bFGF-driven ROS production to promote photoreceptor survival. Using the 661W
photoreceptor-like cell line, we now show that Norgestrel, working through
progesterone receptor membrane complex 1 (PGRMC1); generates an early burst of
pro-survival bFGF-induced ROS. Using the rd10 mouse model of RP, we confirm that
Norgestrel induces a similar early pro-survival increase in retinal ROS.
Norgestrel-driven protection in the rd10 retina was attenuated in the presence of
antioxidants. This study therefore presents an essential role for ROS signalling
in Norgestrel-mediated neuroprotection in vitro and demonstrates that Norgestrel
employs a similar pro-survival mechanism in the degenerating retina.
PMID- 28493651
TI - Hydroxoiridium-Catalyzed Hydroalkylation of Terminal Alkenes with Ureas by C(sp3
)-H Bond Activation.
AB - Direct alkylation of a methyl group, on di- and trisubstituted ureas, with
terminal alkenes by C(sp3 )-H bond activation proceeded in the presence of a
hydroxoiridium/bisphosphine catalyst to give high yields of the corresponding
addition products. The hydroxoiridium/bisphosphine complex generates an
amidoiridium intermediate by reaction with ureas having an N-H bond.
PMID- 28493652
TI - Vitamin D Deficiency Associated With Cognitive Functioning in Psychotic
Disorders.
AB - BACKGROUND: Cognitive dysfunctions are core features of psychotic disorders with
substantial impact on daily functioning. Vitamin D deficiency has been found to
be related to cognitive dysfunctions, but the associations between vitamin D
deficiency and cognition in persons with a psychotic disorder are largely
unknown. METHODS: This cross-sectional study included 225 patients with a DSM-IV
psychotic disorder consecutively recruited from 2003 to 2014 and 159 randomly
selected healthy controls, assessed by a cognitive test battery, a clinical
protocol (including Structured Clinical Interview for DSM-IV Axis I Disorders and
Positive and Negative Syndrome Scale), and a physical examination including
vitamin D measurements. Multiple regression models were performed to evaluate the
effect of vitamin D deficiency (defined serum 25-hydroxyvitamin D [25(OH)D] < 25
nmol/L) on key cognitive domains: processing speed, verbal learning, verbal
memory, and executive functioning. RESULTS: Vitamin D deficiency was
significantly associated with decreased processing speed (ie, Digit Symbol
Coding) (t = -2.6, P = .01; total model: adjusted R2 = 0.40, F6, 374 = 43.8, P <
.001) and decreased fluency (ie, verbal fluency) (t = -2.1, P = .04; total model:
adjusted R2 = 0.35, F6, 373 = 34.2, P < .001) when the results were controlled
for age, ethnicity, IQ, patient versus control status, and substance or alcohol
abuse. Additional analyses indicated that negative symptoms diluted the
association between vitamin D deficiency and processing speed (t = -1.72, P =
.09) and verbal fluency (t = -1.35, P = .18) in patients. CONCLUSION: The
associations between vitamin D deficiency and processing speed and verbal fluency
are good arguments for planning large-scale randomized controlled studies in
target populations so conclusions can be made about the potential beneficial
effect of vitamin D on cognition in psychotic disorders.
PMID- 28493653
TI - Technology-Assisted Parent Training Programs for Children and Adolescents With
Disruptive Behaviors: A Systematic Review.
AB - OBJECTIVE: To systematically review digitally assisted parent training programs
(DPTs) targeting the treatment of children and adolescents with disruptive
behaviors. DATA SOURCES: A search was conducted using PubMed, PsycINFO, and
EMBASE databases for peer-reviewed studies published between January 1, 2000, and
March 1, 2016. Reference lists of included and review articles were searched
manually for additional references. STUDY SELECTION: Broad search terms in
varying combinations for parent, training, technologies, and disruptive behavior
problems were used. We included English-language articles reporting on the
effectiveness of DPTs targeting child or adolescent disruptive behaviors (eg,
conduct disorder, oppositional defiant disorder). DPTs designed to use digital
media or software programs not to be primarily used within a therapy setting (eg,
group, face-to-face) were included. DATA EXTRACTION: Study design, recruitment
and sample characteristics, theoretical background, digital program features,
user's engagement, and measures of child behavior were extracted. RESULTS:
Fourteen intervention studies (n = 2,427, 58% male, 1,500 in DPT conditions, 12
randomized trials) examining 10 programs met inclusion criteria. Interventions
included self-directed noninteractive (eg, podcasts; 3 studies) and interactive
(eg, online software; 4 studies) DPTs, remotely administered DPTs combined with
professional phone-based coaching (2 studies), and a smartphone enhancement of
standard treatment. Interventions were delivered over a mean +/- SD period of 8.7
+/- 4.2 weeks, most (11/14; 78.6%) were remotely administered, and all
recruitment procedures included an outreach for parents outside of mental health
care settings. For programs with > 5 sessions, the mean +/- SD completion rate of
available sessions was 68.6% +/- 13.1%. In comparison to no treatment control,
self-directed programs yielded significant improvements in child behavior for
children (age < 9 years, Cohen d = 0.47-0.80, 4 studies) and adolescents (d =
0.17, 0.20, 2 studies). Overall, reduced professional support combined with DPT
was not inferior to full-contact conditions and showed small improvement in
comparison to usual care (d = 0.34). Preliminary indicators also suggested that
technology enhancements may increase engagement and outcomes of standard
treatment. CONCLUSIONS: The current review indicates the efficacy of DPT across a
range of therapy formats applied in real-world settings demonstrating the
potential for increased accessibility of evidence-based treatment for youth with
disruptive behaviors. Additional studies are needed to extend these findings and
to determine moderating effects of different designs.
PMID- 28493655
TI - Development of a Computerized Adaptive Test Suicide Scale-The CAT-SS.
AB - OBJECTIVE: Current suicide risk screening and measurement are inefficient, have
limited measurement precision, and focus entirely on suicide-related items. For
this study, a psychometric harmonization between related suicide, depression, and
anxiety symptom domains that provides a more balanced and complete spectrum of
suicidal symptomatology was developed. The objective of this article is to
describe the results of the early stages of computerized adaptive testing
development for a suicide scale and pave the way for the final stage of
validation. METHODS: Data from psychiatric outpatients at the University of
Pittsburgh and a community health clinic were collected from January 2010 through
June 2012. 789 participants were enrolled in the calibration phase; 70% were
female, and 30% were male. The rate of major depressive disorder as diagnosed by
DSM-5 was 47%. The item bank contained 1,008 items related to depression,
anxiety, and mania, including 11 suicide items. Data were analyzed using a
bifactor model to identify a core dimension between suicidal ideation,
depression, anxiety, and mania items. A computerized adaptive test was developed
via simulation from the actual complete item responses in 308 subjects. RESULTS:
111 items were identified that provided an extension of suicidality assessment to
include statistically related responses from depression and anxiety domains that
are syndromally associated with suicidality. All items had high loadings on the
primary suicide dimension (average = 0.67; range, 0.49-0.88). Analyses revealed
that a mean of 10 items (5-20) had a correlation of 0.96 with the 111-item scale,
with a precision of 5 points on a 100-point scale metric. Preliminary validation
data based on 290 clinician interviews revealed a 52-fold increase in the
likelihood of current suicidal ideation across the range of the Computerized
Adaptive Test Suicide Scale (CAT-SS). CONCLUSIONS: The CAT-SS is able to
accurately measure the latent suicide dimension with a mean of 10 items in
approximately 2 minutes. Further validation against an independent clinician
administered assessment of suicide risk (ideation and attempts) and prediction of
suicidal behavior is underway.
PMID- 28493654
TI - The US Food and Drug Administration's Perspective on the New Antipsychotic
Pimavanserin.
AB - OBJECTIVE: To summarize the US Food and Drug Administration's (FDA's) review of
the safety and effectiveness for pimavanserin, an atypical antipsychotic, for the
treatment of hallucinations and delusions associated with Parkinson's disease
psychosis. We describe the regulatory and clinical issues important to the FDA's
approval of this New Drug Application, with special focus on the risk-benefit
balance. We also describe a new labeling feature that presents additional
efficacy data to clinicians. DATA SOURCES: Data sets for all relevant clinical
trials of pimavanserin and the Applicant's and FDA's analyses of these data were
considered in this review. Data were available from 616 patients with Parkinson's
disease with hallucinations and delusions who received at least 1 dose of
pimavanserin, with a total exposure of 825 patient-years in the Parkinson's
disease psychosis population. RESULTS: Pimavanserin 34 mg/d was effective in
treating hallucinations and delusions associated with Parkinson's disease. In the
Applicant's single pivotal trial, 80.5% of pimavanserin patients experienced at
least some improvement in symptoms compared to 58.1% of patients taking placebo.
Pimavanserin did not worsen motor function, an adverse effect commonly observed
with other antipsychotics, probably because of a lack of consequential dopamine
binding. CONCLUSIONS: Pimavanserin is the only FDA-approved treatment for the
hallucinations and delusions seen in patients with psychosis of Parkinson's
disease. Although pimavanserin appears to have a pharmacologic mechanism that is
different from other atypical antipsychotics, concern remained that the increased
risk of death seen with antipsychotic use in elderly demented patients, and
described in all approved antipsychotic labels, would also occur with
pimavanserin. Pimavanserin bears the same boxed warning about the risk of death
associated with antipsychotic use in elderly patients with dementia.
PMID- 28493656
TI - Perceived Stigma and Quality of Life in Patients Following Recovery From
Delirium.
AB - OBJECTIVE: To elucidate the factors related to perceived stigma and quality of
life (QoL) in patients who have recovered from delirium. METHODS: This
prospective cohort investigation of patients with delirium, as diagnosed
according to DSM-IV-TR criteria, was conducted from July 2011 to May 2013. The
perceived stigma level and QoL of each patient was assessed using the Perceived
Stigma of Delirium Scale (PSDS) and European Quality of Life Visual Analog Scale
(EQ-VAS), respectively, following recovery from delirium. Several clinical
characteristics were assessed at baseline and after recovery from delirium, and a
multivariate linear regression analysis was conducted. RESULTS: This study
included 128 patients who completed a follow-up assessment after recovery from
delirium. A multivariate analysis revealed that patients who had a history of
depression (B = 3.34, P = .026), could recall their experiences with delirium (B
= 1.71, P = .011), and had a longer duration from delirium detection to recovery
(B = 1.39, P = .012) obtained higher PSDS scores than patients without these
characteristics. The ability to recall delirium experiences (B = -7.17, P = .026)
and the use of antipsychotics at follow-up assessment (B = -7.87, P = .039) were
associated with lower EQ-VAS scores. Additionally, PSDS scores were negatively
correlated with EQ-VAS scores (r = -0.37, P < .001). CONCLUSIONS: This study
found that patients who experienced an episode of delirium reported varying
degrees of perceived stigma and that the ability to recall their delirium
experiences was associated with a higher stigma and a poorer QoL. These findings
suggest that care teams should pay more attention to perceived stigma in patients
with delirium.
PMID- 28493657
TI - Introduction.
AB - We are pleased to bring you the second of two special issues on mood and anxiety
disorders focussing on data from the 2014 Survey on Living with Chronic Diseases
in Canada-Mood and Anxiety Disorder Component (SLCDC-MA). In December of 2016, we
published the first issue, which included three articles describing various
aspects of Canadian adults with a self-reported diagnosed mood and/or anxiety
disorder including their sociodemographic characteristics, health status,
activity limitations and level of disability and factors associated with well
being. The three articles in this (second) issue investigate topics related to
the management of these disorders. Collectively, the articles explore key
sociodemographic factors known to influence health-related outcomes and discuss
strategies aimed at promoting the recovery and well-being of Canadian adults with
a self-reported mood and/or anxiety disorder diagnosis.
PMID- 28493658
TI - Factors associated with delayed diagnosis of mood and/or anxiety disorders.
AB - INTRODUCTION: This study examined the association between time to diagnosis and
sociodemographic and clinical characteristics as well as time to diagnosis and
physical and mental health status, among Canadian adults with a self-reported
mood and/or anxiety disorder diagnosis. METHODS: We used data from the 2014
Survey on Living with Chronic Diseases in Canada-Mood and Anxiety Disorders
Component. The study sample (n=3212) was divided into three time to diagnosis
subgroups: long (> 5 years), moderate (1-5 years) and short (< 1 year). We
performed descriptive and multinomial multivariate logistic regression analyses.
Estimates were weighted to represent the Canadian adult household population
living in the 10 provinces with diagnosed mood and/or anxiety disorders. RESULTS:
The majority (61.6%) of Canadians with a mood and/or anxiety disorder diagnosis
reported having received their diagnosis more than one year after symptom onset
(30.0% reported a moderate delay and 31.6% a long delay). Upon controlling for
individual characteristics, we found significant associations between a moderate
delay and having no or few physical comorbidities; a long delay and older age;
and both moderate and long delays and early age of symptom onset. In addition, a
long delay was significantly associated with "poor" or "fair" perceived mental
health and the greatest number of activity limitations. CONCLUSION: These
findings affirm that a long delay in diagnosis is associated with negative health
outcomes among Canadian adults with mood and/or anxiety disorders. Time to
diagnosis is particularly suboptimal among older adults and people with early
symptom onset. Tailored strategies to facilitate an early diagnosis for those at
greatest risk of a delayed diagnosis, especially for those with early symptom
onset, are needed.
PMID- 28493659
TI - Self-management of mood and/or anxiety disorders through physical
activity/exercise.
AB - INTRODUCTION: Physical activity/exercise is regarded as an important self
management strategy for individuals with mental illness. The purpose of this
study was to describe individuals with mood and/or anxiety disorders who were
exercising or engaging in physical activity to help manage their disorders versus
those who were not, and the facilitators for and barriers to engaging in physical
activity/exercise. METHODS: For this study, we used data from the 2014 Survey on
Living with Chronic Diseases in Canada-Mood and Anxiety Disorders Component.
Selected respondents (n = 2678) were classified according to the frequency with
which they exercised: (1) did not exercise; (2) exercised 1 to 3 times a week; or
(3) exercised 4 or more times a week. We performed descriptive and multinomial
multiple logistic regression analyses. Estimates were weighted to represent the
Canadian adult household population living in the 10 provinces with diagnosed
mood and/or anxiety disorders. RESULTS: While 51.0% of the Canadians affected
were not exercising to help manage their mood and/or anxiety disorders, 23.8%
were exercising from 1 to 3 times a week, and 25.3% were exercising 4 or more
times a week. Increasing age and decreasing levels of education and household
income adequacy were associated with increasing prevalence of physical
inactivity. Individuals with a mood disorder (with or without anxiety) and those
with physical comorbidities were less likely to exercise regularly. The most
important factor associated with engaging in physical activity/exercise was to
have received advice to do so by a physician or other health professional. The
most frequently cited barriers for not exercising at least once a week were as
follows: prevented by physical condition (27.3%), time constraints/too busy
(24.1%) and lack of will power/self-discipline (15.8%). CONCLUSION: Even though
physical activity/exercise has been shown beneficial for depression and anxiety
symptoms, a large proportion of those with mood and/or anxiety disorders did not
exercise regularly, particularly those affected by mood disorders and those with
physical comorbidities. It is essential that health professionals recommend
physical activity/exercise to their patients, discuss barriers and support their
engagement.
PMID- 28493661
TI - Letter to the Editor - The implications of the professionalization of health
promotion in Canada: a response to JR Graham's letter to the editor.
AB - This letter is in response to the following Letter to the Editor: http://www.phac
aspc.gc.ca/publicat/hpcdp-pspmc/37-1/ar-04-eng.php.
PMID- 28493662
TI - Implementing the New ANA Standard 8: Culturally Congruent Practice
AB - The American Nurses Association (ANA) is responsible for the contract between
society and the nursing profession, including the nursing scope and standards of
practice. In 2015, an ANA workgroup produced Nursing: Scope and Standards of
Practice, 3rd Ed during a time of social change and an increase of culturally and
ethnically diverse consumers. Subsequently, a subset of workgroup members and an
invited transcultural nursing expert led to the creation of the new Standard 8:
Culturally Congruent Practice, describing nursing care that is in agreement with
the preferred values, beliefs, worldview, and practices of the healthcare
consumer. This article records the history of the revised scope and standards and
new Standard 8, the reasoning behind this standard and its impact on nursing
practice, education, and research. The article also guides nurses in the
application of Standard 8 to nursing practice and offers discussion about
implementing culturally congruent practice through the nursing process. We also
discuss cultural congruence for the graduate-prepared nurse; offer brief comments
related to evaluation of culturally congruent practice using Standard 8 and
future research; and conclude with a call to action.
PMID- 28493660
TI - Use of medication and psychological counselling among Canadians with mood and/or
anxiety disorders.
AB - INTRODUCTION: This study describes the use of prescription medications and
psychological counselling in the past 12 months among Canadian adults with a self
reported mood and/or anxiety disorder diagnosis; the sociodemographic and
clinical characteristics associated with their use; and reasons for not using
them. METHODS: We used data from the 2014 Survey on Living with Chronic Diseases
in Canada-Mood and Anxiety Disorders Component. The study sample (n = 2916) was
divided into four treatment subgroups: (1) taking medication only; (2) having
received counselling only; (3) both; or (4) neither. We combined the first three
subgroups and carried out descriptive and multivariate logistic regression
analyses comparing those who are taking medication and/or have received
counselling in the past 12 months, versus those doing neither. Estimates were
weighted to represent the Canadian adult household population living in the 10
provinces with diagnosed mood and/or anxiety disorders. RESULTS: The majority
(81.8%) of Canadians with a mood and/or an anxiety disorder diagnosis reported
they are taking medications and/or have received counselling (47.6% taking
medications only; 6.9% received counselling only; and 27.3% taking/having
received both). Upon controlling for individual characteristics, taking
medications and/or having received counselling was significantly associated with
older age; higher household income; living in the Atlantic region or Quebec
versus Ontario; and having concurrent disorders or mood disorders only. Symptoms
controlled without medication was the most common reason for not taking
medications, while preferring to manage on their own and taking medications were
among the common reasons for not having received counselling. CONCLUSION: The
majority of Canadian adults with a mood and/or an anxiety disorder diagnosis are
taking medications, while few have received counselling. Insights gained
regarding the factors associated with these treatments, and reasons for not using
them, emphasize the importance of discussing treatment options and perceived
barriers with patients to ensure they receive the best treatment according to
their needs and preference.
PMID- 28493663
TI - Gate-Tunable Electron Injection Based Organic Light-Emitting Diodes for Low-Cost
and Low-Voltage Active Matrix Displays.
AB - Low-cost and low-voltage active matrix displays were fabricated by simply
patterning gate electrode arrays on a polymer electrolyte (PE)-coated polymer
light-emitting diode (PLED). Structurally, a PE capacitor seamlessly stacked on a
PLED by sharing a common Al:LiF composite electrode (PEC|PLED). This monolithic
integrated organic optoelectronic device was characterized and interpreted as the
tunable work function (surface potential) because of the perturbation of
accumulated ions on Al:LiF composite electrode by PEC charging and discharging.
The modulation of electron injection by the PEC resulted in increases in the
electroluminescent brightness, from <100 cd m-2 to >8000 cd m-2, and the external
quantum efficiency from <0.025% to 2.4%.
PMID- 28493664
TI - Structure and Spectroscopy of Alkene-Cleaving Dioxygenases Containing an
Atypically Coordinated Non-Heme Iron Center.
AB - Carotenoid cleavage oxygenases (CCOs) are non-heme iron enzymes that catalyze
scission of alkene groups in carotenoids and stilbenoids to form biologically
important products. CCOs possess a rare four-His iron center whose resting-state
structure and interaction with substrates are incompletely understood. Here, we
address this knowledge gap through a comprehensive structural and spectroscopic
study of three phyletically diverse CCOs. The crystal structure of a fungal
stilbenoid-cleaving CCO, CAO1, reveals strong similarity between its iron center
and those of carotenoid-cleaving CCOs, but with a markedly different substrate
binding cleft. These enzymes all possess a five-coordinate high-spin Fe(II)
center with resting-state Fe-His bond lengths of ~2.15 A. This ligand set
generates an iron environment more electropositive than those of other non-heme
iron dioxygenases as observed by Mossbauer isomer shifts. Dioxygen (O2) does not
coordinate iron in the absence of substrate. Substrates bind away (~4.7 A) from
the iron and have little impact on its electronic structure, thus excluding
coordination-triggered O2 binding. However, substrate binding does perturb the
spectral properties of CCO Fe-NO derivatives, indicating proximate organic
substrate and O2-binding sites, which might influence Fe-O2 interactions.
Together, these data provide a robust description of the CCO iron center and its
interactions with substrates and substrate mimetics that illuminates
commonalities as well as subtle and profound structural differences within the
CCO family.
PMID- 28493667
TI - Scaffold Diversity from N-Acyliminium Ions.
AB - N-Acyliminium ions are powerful reactive species for the formation of carbon
carbon and carbon-heteroatom bonds. Strategies relying on intramolecular
reactions of N-acyliminium intermediates, also referred to as N-acyliminium ion
cyclization reactions, have been employed for the construction of structurally
diverse scaffolds, ranging from simple bicyclic skeletons to complex polycyclic
systems and natural-product-like compounds. This review aims to provide an
overview of cyclization reactions of N-acyliminium ions derived from various
precursors for the assembly of structurally diverse scaffolds, covering the
literature over the past 12 years (from 2004 to 2015).
PMID- 28493666
TI - Flexible Transparent Supercapacitors Based on Hierarchical Nanocomposite Films.
AB - Flexible transparent electronic devices have recently gained immense popularity
in smart wearable electronics and touch screen devices, which accelerates the
development of the portable power sources with reliable flexibility, robust
transparency and integration to couple these electronic devices. For potentially
coupled as energy storage modules in various flexible, transparent and portable
electronics, the flexible transparent supercapacitors are developed and assembled
from hierarchical nanocomposite films of reduced graphene oxide (rGO) and aligned
polyaniline (PANI) nanoarrays upon their synergistic advantages. The
nanocomposite films are fabricated from in situ PANI nanoarrays preparation in a
blended solution of aniline monomers and rGO onto the flexible, transparent, and
stably conducting film (FTCF) substrate, which is obtained by coating silver
nanowires (Ag NWs) layer with Meyer rod and then coating of rGO layer on
polyethylene terephthalate (PET) substrate. Optimization of the transparency, the
specific capacitance, and the flexibility resulted in the obtained all-solid
state nanocomposite supercapacitors exhibiting enhanced capacitance performance,
good cycling stability, excellent flexibility, and superior transparency. It
provides promising application prospects for exploiting flexible, low-cost,
transparent, and high-performance energy storage devices to be coupled into
various flexible, transparent, and wearable electronic devices.
PMID- 28493665
TI - MnO2 Nanotube-Based NanoSearchlight for Imaging of Multiple MicroRNAs in Live
Cells.
AB - Sensitive assay and imaging of multiple low-abundance microRNAs (miRNAs) in
living cells remain a grand challenge. Herein, based on polyelectrolyte-induced
reduction, a facile approach has been proposed to synthesize novel MnO2
nanotubes. Owing to the remarkably strong fluorescence quenching ability, low
cytotoxicity, and excellent colloid stability, the as-prepared MnO2 nanotubes
showed great potential for simultaneous detection and imaging of multiple miRNAs
in vitro and in situ in living cells for the first time. Besides, MnO2 nanotubes
can be reduced to Mn2+ by intracellular acid pH or glutathione, which may serve
as an activatable contrast reagent for MRI. Therefore, the MnO2 nanotube-based
probes, termed "NanoSearchlight", provide a promising, multimodal imaging tool
for precise and accurate diagnosis and prognosis of cancers.
PMID- 28493668
TI - Photothermal Effect Induced Negative Photoconductivity and High Responsivity in
Flexible Black Phosphorus Transistors.
AB - This paper reports negative photoconductivity mechanism in flexible black
phosphorus (BP) transistors built on freestanding polyimide film. Near-infrared
laser (lambda = 830 nm) excitation leads to significantly suppressed device on
state current with a very high responsivity of up to 53 A/W. The underlying
mechanism of the negative photoconductivity is attributed to the strong
photothermal effect induced by the low thermal conductivity of the polyimide
substrate used. The heat generated by the infrared light illumination results in
enhanced phonon scattering, reduced carrier mobility, and consequently negative
photocurrent. Such a phenomenon was not observed in similar BP devices built on
SiO2/Si substrates whose thermal conductivity is much higher. The above
photothermal mechanism is also supported by temperature-dependent electrical
characterization and device simulation. Such a flexible BP infrared photodetector
with ultrahigh responsivity may find potential applications in future wearable
and biointegrated imaging systems.
PMID- 28493670
TI - Speed up Ferroelectric Organic Transistor Memories by Using Two-Dimensional
Molecular Crystalline Semiconductors.
AB - Ferroelectric organic field-effect transistors (Fe-OFETs) have attracted
intensive attention because of their promising potential in nonvolatile memory
devices. The quick switching between binary states is a significant fundamental
feature in evaluating Fe-OFET memories. Here, we employ 2D molecular crystals via
a solution-based process as the conducting channels in transistor devices, in
which ferroelectric polymer acts as the gate dielectric. A high carrier mobility
of up to 5.6 cm2 V-1 s-1 and a high on/off ratio of 106 are obtained. In
addition, the efficient charge injection by virtue of the ultrathin 2D molecular
crystals is beneficial in achieving rapid operations in the Fe-OFETs; devices
exhibit short switching time of ~2.9 and ~3.0 ms from the on- to the off-state
and from the off- to the on-state, respectively. Consequently, the presented
strategy is capable of speeding up Fe-OFET memory devices by using solution
processed 2D molecular crystals.
PMID- 28493669
TI - Amyloid-like Fibrils from an alpha-Helical Transmembrane Protein.
AB - The propensity to misfold and self-assemble into stable aggregates is
increasingly being recognized as a common feature of protein molecules. Our
understanding of this phenomenon and of its links with human disease has improved
substantially over the past two decades. Studies thus far, however, have been
almost exclusively focused on cytosolic proteins, resulting in a lack of detailed
information about the misfolding and aggregation of membrane proteins. As a
consequence, although such proteins make up approximately 30% of the human
proteome and have high propensities to aggregate, relatively little is known
about the biophysical nature of their assemblies. To shed light on this issue, we
have studied as a model system an archetypical representative of the ubiquitous
major facilitator superfamily, the Escherichia coli lactose permease (LacY). By
using a combination of established indicators of cross-beta structure and
morphology, including the amyloid diagnostic dye thioflavin-T, circular dichroism
spectroscopy, Fourier transform infrared spectroscopy, X-ray fiber diffraction,
and transmission electron microscopy, we show that LacY can form amyloid-like
fibrils under destabilizing conditions. These results indicate that transmembrane
alpha-helical proteins, similarly to cytosolic proteins, have the ability to
adopt this generic state.
PMID- 28493672
TI - Correction to "Living Biomaterials".
PMID- 28493671
TI - Cationic Polythiophenes as Gene Delivery Enhancer.
AB - There is urgent demand of easily available and highly effective method to improve
transgene performance of polymeric gene carriers at low consumption of delivery
materials. We developed biocompatible multicomponent nanocomposites in which
small quantities of cationic polythiophenes were engineered into the outer shell
of polypeptide/DNA polyplexes without covalent linkages. We revealed the
introduction of polythiophenes in small quantities led to multiple outcomes
including modulation of polyplex size and zeta potential, increase in polyplex
stability, promotion of endolysosome membrane disruption, light-induced
generation of reactive oxygen species (ROS), and significant enhancement of gene
delivery to tumor cells. The factors such as structural architectures, molecular
weights, photosensitizing capability, and percentage composition of
polythiophenes were investigated.
PMID- 28493673
TI - Controlled Crystal Grain Growth in Mixed Cation-Halide Perovskite by Evaporated
Solvent Vapor Recycling Method for High Efficiency Solar Cells.
AB - We developed a new and simple solvent vapor-assisted thermal annealing (VA)
procedure which can reduce grain boundaries in a perovskite film for fabricating
highly efficient perovskite solar cells (PSCs). By recycling of solvent molecules
evaporated from an as-prepared perovskite film as a VA vapor source, named the
pot-roast VA (PR-VA) method, finely controlled and reproducible device
fabrication was achieved for formamidinium (FA) and methylammonium (MA) mixed
cation-halide perovskite (FAPbI3)0.85(MAPbBr3)0.15. The mixed perovskite was
crystallized on a low-temperature prepared brookite TiO2 mesoporous scaffold.
When exposed to very dilute solvent vapor, small grains in the perovskite film
gradually unified into large grains, resulting in grain boundaries which were
highly reduced and improvement of photovoltaic performance in PSC. PR-VA-treated
large grain perovskite absorbers exhibited stable photocurrent-voltage
performance with high fill factor and suppressed hysteresis, achieving the best
conversion efficiency of 18.5% for a 5 * 5 mm2 device and 15.2% for a 1.0 * 1.0
cm2 device.
PMID- 28493674
TI - Surface Enhanced Spatially Offset Raman Spectroscopy Detection of Neurochemicals
Through the Skull.
AB - The ability to noninvasively detect neurotransmitters through the skull would aid
in understanding brain function and the development of neurological diseases.
Surface enhanced spatially offset Raman spectroscopy (SESORS) is a powerful
technique that combines the sensitivity of surface-enhanced Raman spectroscopy
(SERS) with the ability of spatially offset Raman spectroscopy (SORS) to probe
subsurface layers. Here we present SERS measurements of neurotransmitters
(melatonin, serotonin, and epinephrine) at various concentrations followed by the
SESORS measurements of the neurotransmitters to a concentration as low as 100 MUM
in a brain tissue mimic through a cat skull. Principal components analysis was
performed to distinguish between the surface bone layer and the subsurface layer,
comprised of a brain tissue mimic modified with neurotransmitters, and to
determine if each individual neurotransmitter could be accurately identified.
PMID- 28493675
TI - Investigation of Thermal Stability of P2-NaxCoO2 Cathode Materials for Sodium Ion
Batteries Using Real-Time Electron Microscopy.
AB - Here, we take advantage of in situ transmission electron microscopy (TEM) to
investigate the thermal stability of P2-type NaxCoO2 cathode materials for sodium
ion batteries, which are promising candidates for next-generation lithium ion
batteries. A double-tilt TEM heating holder was used to directly characterize the
changes in the morphology and the crystallographic and electronic structures of
the materials with increase in temperature. The electron diffraction patterns and
the electron energy loss spectra demonstrated the presence of cobalt oxides
(Co3O4, CoO) and even metallic cobalt (Co) at higher temperatures as a result of
reduction of Co ions and loss of oxygen. The bright-field TEM images revealed
that the surface of NaxCoO2 becomes porous at high temperatures. Higher cutoff
voltages result in degrading thermal stability of NaxCoO2. The observations
herein provide a valuable insight that thermal stability is one of the important
factors to be considered in addition to the electrochemical properties when
developing new electrode materials for novel battery systems.
PMID- 28493676
TI - Skin Sensitization QMM for HRIPT NOEL Data: Aldehyde Schiff-Base Domain.
AB - The general chemistry principles underlying skin sensitization for Schiff base
(SB) electrophiles may be used to develop a quantitative mechanistic model (QMM),
based on reactivity supplemented with a hydrophobicity parameter for some but not
all structures within the SB reaction domain. For aliphatic Schiff base
electrophiles, the log of the no observed effect level (NOEL) values (pNOEL) from
the human repeated insult patch test (HRIPT) can be calculated by the reactivity
parameter summation of sigma star values (Sigmasigma*) and a hydrophobicity
parameter (logP). Specifically, the QMM, pNOEL = 2.34(+/-0.33) Sigmasigma* +
0.19(+/-0.07) logP - 2.62(+/-0.22), n = 19, R2 = 0.77, R2(adj) = 0.74, s = 0.20,
F = 27, was developed. Not all parts of the Schiff base domain are modeled with
one equation. Particularly, predicting aromatic aldehydes and ketones appears to
require a separate equation. Interestingly, the same physical organic chemical
properties originally applied to modeling the local lymph node assay potency of
Schiff base electrophiles apply to human potency as represented by the HRIPT.
PMID- 28493677
TI - The N6-Position of Adenine Is a Blind Spot for TAL-Effectors That Enables
Effective Binding of Methylated and Fluorophore-Labeled DNA.
AB - Transcription-activator-like effectors (TALEs) are programmable DNA binding
proteins widely used for genome targeting. TALEs consist of multiple concatenated
repeats, each selectively recognizing one nucleobase via a defined repeat
variable diresidue (RVD). Effective use of TALEs requires knowledge about their
binding ability to epigenetic and other modified nucleobases occurring in target
DNA. However, aside from epigenetic cytosine-5 modifications, the binding ability
of TALEs to modified DNA is unknown. We here study the binding of TALEs to the
epigenetic nucleobase N6-methyladenine (6mA) found in prokaryotic and recently
also eukaryotic genomes. We find that the natural, adenine (A)-binding RVD NI is
insensitive to 6mA. Model-assisted structure-function studies reveal
accommodation of 6mA by RVDs with altered hydrophobic surfaces and abilities of
hydrogen bonding to the N6-amino group or N7 atom of A. Surprisingly, this
tolerance of N6 substitution was transferrable to bulky N6-alkynyl substituents
usable for click chemistry and even to a large rhodamine dye, establishing the N6
position of A as the first site of DNA that offers label introduction within TALE
target sites without interference. These findings will guide future in vivo
studies with TALEs and expand their applicability as DNA capture probes for
analytical applications in vitro.
PMID- 28493678
TI - Deciphering the Structural Relationships of Five Cd-Based Metal-Organic
Frameworks.
AB - The one-pot reaction of Cd(NO3)2.4H2O and 5-(6-(hydroxymethyl)pyridin-3
yl)isophthalic acid (H2L) in DMF/H2O (DMF = N,N-dimethylformamide) produced a two
dimensional (2D) metal-organic framework (MOF) of [Cd(L)(H2O)2] (A) bearing aqua
bridged Cd centers, accompanied by two three-dimensional (3D) MOFs
[Cd(L)(DMF)0.5] (B) and [Cd(L)] (C). Removing the bridging aqua molecules of A by
heating led to the formation of an additional 3D MOF of [Cd(L)] (D) in a single
crystal to single-crystal (SCSC) manner. The search for the preceding compound
that could convert to A resulted in the isolation of a 2D MOF [Cd(L)(DMF)] (E)
that readily converted to A in water, but with the loss of single crystallinity.
Upon excitation at 350 nm, A, D, E, and the ligand H2L fluoresced at 460 nm, 468
nm, 475 nm, and 411 nm, respectively. The fluorescence of A could be used for the
selective detection of Fe3+ in water down to 0.58 ppm. This quenching was not
affected by the presence of other common metal ions.
PMID- 28493679
TI - Light-Induced Fluorescence Modulation of Quantum Dot-Crystal Violet Conjugates:
Stochastic Off-On-Off Cycles for Multicolor Patterning and Super-Resolution.
AB - Photoswitching or modulation of quantum dots (QDs) can be promising for many
fields that include display, memory, and super-resolution imaging. However, such
modulations have mostly relied on photomodulations of conjugated molecules in QD
vicinity, which typically require high power of high energy photons at UV. We
report a visible light-induced facile modulation route for QD-dye conjugates. QD
crystal violets conjugates (QD-CVs) were prepared and the crystal violet (CV)
molecules on QD quenched the fluorescence efficiently. The fluorescence of QD-CVs
showed a single cycle of emission burst as they go through three stages of (i)
initially quenched "off" to (ii) photoactivated "on" as the result of chemical
change of CVs induced by photoelectrons from QD and (iii) back to photodarkened
"off" by radical-associated reactions. Multicolor on-demand photopatterning was
demonstrated using QD-CV solid films. QD-CVs were introduced into cells, and
excitation with visible light yielded photomodulation from "off" to "on" and
"off" by nearly ten fold. Individual photoluminescence dynamics of QD-CVs was
investigated using fluorescence correlation spectroscopy and single QD emission
analysis, which revealed temporally stochastic photoactivations and
photodarkenings. Exploiting the stochastic fluorescence burst of QD-CVs,
simultaneous multicolor super-resolution localizations were demonstrated.
PMID- 28493680
TI - Legacy and Current-Use Insecticides in Agricultural Sediments from South China:
Impact of Application Pattern on Occurrence and Risk.
AB - Legacy and current-use insecticides were analyzed in sediments collected from a
typical rice-planting region in South China. Total concentrations of insecticides
varied from 1.63 to 775 ng g-1 with mean and median values of 67.0 and 11.5 ng g
1, respectively. Pyrethroids predominated pesticide composition (31.7%), followed
by organophosphates (23.0%) and fiproles (20.8%). Sediment risk analysis showed
that pyrethroids, fiproles, and abamectin posed significant risk to benthic
invertebrates in one-third of sediments. Different distributions of pyrethroids
and organophosphates in urban and agricultural areas were consistent with their
application patterns, whereas legacy organochlorine pesticides showed no region
specific distribution because of rapid transition of land use pattern from
agricultural to urban areas. Likely illegal use of pyrethroids and fipronil
caused serious ecological risks in agricultural waterways. Pyrethroids and
fipronil were restricted to use in paddy fields, but their occurrence and risk in
agricultural waterways were high, calling for better measures to regulate the
illegal use of insecticides.
PMID- 28493681
TI - Self-Assembled Molecular Hybrids of CoS-DNA for Enhanced Water Oxidation with Low
Cobalt Content.
AB - Water oxidation in alkaline medium was efficiently catalyzed by the self
assembled molecular hybrids of CoS-DNA that had 20 times lower Co loading than
the commonly used loading. The morphological outcome was directed by varying the
molar ratio of metal precursor Co(Ac)2 and DNA and three different sets of CoS
DNA molecular hybrids, viz. CoS-DNA(0.036), CoS-DNA(0.06), and CoS-DNA(0.084)
were prepared. These morphologically distinct hybrids had shown similar
electrocatalytic behavior, because of the fact that they all contained the same
cobalt content. The CoS-DNA(0.036), CoS-DNA(0.06), and CoS-DNA(0.084) required
very low overpotentials of 350, 364, and 373 mV at a current density of 10 mA cm
2 (1 M KOH), respectively. The advantages of lower overpotential, lower Tafel
slope (42.7 mV dec-1), high Faradaic efficiency (90.28%), high stability and
reproducibility after all, with a lower cobalt loading, have certainly shown the
worth of these molecular hybrids in large-scale water oxidation. Moreover, since
DNA itself a good binder, CoS-DNA molecular hybrids were directly casted on
substrate electrodes and used after drying. It also showed minimum intrinsic
resistance as DNA is a good ionic and electronic conductor. Besides, the present
method may also be extended for the preparation of other active electrocatalysts
for water splitting.
PMID- 28493682
TI - A New Split Charge Equilibration Model and REPEAT Electrostatic Potential Fitted
Charges for Periodic Frameworks with a Net Charge.
AB - Periodic frameworks that possess a net charge, such as zeolites, are an important
class of materials in wide use. For guest-host interactions to be simulated in
these materials, partial atomic charges are often used. In this work, we
investigate two methods for the generation of partial atomic charges in periodic
systems having a net framework charge. We first examine the validity of
generating REPEAT electrostatic potential fitted charges derived from periodic
electronic structure calculations, where a constant background charge is added to
neutralize the net charge on the framework. The constant background charge
obviates the need to add neutralizing counterions, which may induce artifacts
such as polarization in the infinite periodic system. The second method we
explore is the split charge equilibration (SQE) method for the rapid generation
of partial atomic charges. The original formulation of the SQE method cannot be
applied to systems with a net charge. In this work, we reformulate the SQE method
by transforming the split charges into an atomic charge basis that allows for non
neutral systems to be treated. The new SQE model, which we call SQEAB (for atomic
basis), was validated with a series of tests using both charged and neutral metal
organic frameworks and zeolites. It was shown that SQEAB gives equivalent results
to those of the original SQE model for neutral systems. We then demonstrated that
the SQEAB method is able to "capture" the chemical structure of a charged
framework better than that of the charge equilibration model by comparing to
REPEAT electrostatic potential fitted charges.
PMID- 28493683
TI - Plant Uptake and Metabolism of Nitrofuran Antibiotics in Spring Onion Grown in
Nitrofuran-Contaminated Soil.
AB - Environmental pollution caused by the discharge of mutagenic and carcinogenic
nitrofurans to the aquatic and soil environment is an emerging public health
concern because of the potential in producing drug-resistant microbes and being
uptaken by food crops. Using liquid chromatography-tandem mass spectrometry
analysis and with spring onion (Allium wakegi Araki) as the plant model, we
investigated in this study the plant uptake and accumulation of nitrofuran from a
contaminated environment. Our study revealed for the first time high uptake and
accumulation rates of nitrofuran in the edible parts of the food crop.
Furthermore, results indicated highly efficient plant metabolism of the absorbed
nitrofuran within the plant, leading to the formation of genotoxic hydrazine
containing metabolites. The results from this study may disclose a previously
unidentified human exposure pathway through contaminated food crops.
PMID- 28493684
TI - What Makes a Density Functional Approximation Good? Insights from the Left Fukui
Function.
AB - This work proposes, justifies, and reports tests of the chemically relevant left
Fukui function of Li, C, and F on a range of density functional approximations.
Analysis indicates that functionals can be good at densities and bad at Fukui
functions, and vice versa, analogous with energies and ionization potentials.
"TPSSh", "SOGGA11X", and "B2PLYP" are star performers on both, however. Many
"Minnesota functionals" fare much better here than in a recent analysis of
electron densities. In this context, new optimizing strategies are mentioned.
PMID- 28493686
TI - First Do No Harm: The Need to Explore Potential Adverse Health Implications of
Drinking Rainwater.
PMID- 28493685
TI - Selective Detection of Shiga-like Toxin 1 from Complex Samples Using Pigeon
Ovalbumin Functionalized Gold Nanoparticles as Affinity Probes.
AB - Escherichia coli O157:H7 is a foodborne pathogen. This bacterial strain can
generate Shiga-like toxins (SLTs), which can cause serious sickness and even
death. Thus, it is important to develop effective and sensitive methods that can
be used to rapidly identify the presence of SLTs from complex samples. Pigeon egg
white (PEW) contains abundant glycoproteins, including pigeon ovalbumin (POA)
(~60%). POA possesses Gal-alpha(1->4)-Gal-beta(1->4)-GlcNAc termini, which can
recognize the B subunits in SLT type 1 (SLT-1B). Thus, POA is a suitable probe
for trapping SLT-1B. In this work, we used PEW proteins as starting materials to
react with aqueous tetrachloroauric acid for generation of PEW-protein
immobilized gold nanoparticles (AuNPs@PEW) via one-pot reactions. We demonstrated
that the generated AuNPs@PEW were mainly dominated by POA-immobilized Au NPs. The
as-prepared AuNPs@PEW were used as affinity probes to selectively probe SLT-1B
from complex cell lysates derived from E. coli O157:H7. The selective trapping
step can be completed within ~90 s under microwave heating (power = 450 W) to
enrich sufficient SLT-1B for matrix-assisted laser desorption/ionization (MALDI)
mass spectrometric analysis. Furthermore, this approach can be used to detect SLT
1B at a concentration as low as ~40 pM. The feasibility of using the proposed
method to selectively detect SLT-1B from ham contaminated by E. coli O157:H7 was
also demonstrated.
PMID- 28493687
TI - Comparative Metabolic Response between Cucumber ( Cucumis sativus) and Corn ( Zea
mays) to a Cu(OH)2 Nanopesticide.
AB - Due to their unique properties, copper-based nanopesticides are emerging in the
market. Thus, understanding their effect on crop plants is very important.
Metabolomics can capture a snapshot of cellular metabolic responses to a
stressor. We selected maize and cucumber as model plants for exposure to
different doses of Cu(OH)2 nanopesticide. GC-TOF-MS-based metabolomics was
employed to determine the metabolic responses of these two species. Results
revealed significant differences in metabolite profile changes between maize and
cucumber. Furthermore, the Cu(OH)2 nanopesticide induced metabolic reprogramming
in both species, but in different manners. In maize, several intermediate
metabolites of the glycolysis pathway and tricarboxylic acid cycle (TCA) were up
regulated, indicating the energy metabolism was activated. In addition, the
levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and
their precursors (phenylalanine, tyrosine) were enhanced, indicating the
activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an
antioxidant defense-related pathway. In cucumber, arginine and proline metabolic
pathways were the most significantly altered pathway. Both species exhibited
altered levels of fatty acids and polysaccharides, suggesting the cell membrane
and cell wall composition may change in response to Cu(OH)2 nanopesticide. Thus,
metabolomics helps to deeply understand the differential response of these plants
to the same nanopesticide stressor.
PMID- 28493688
TI - Isolation and Characterization of a Human Intestinal Bacterium Eggerthella sp.
AUH-JLD49s for the Conversion of (-)-3'-Desmethylarctigenin.
AB - Arctiin is the most abundant bioactive compound contained in the Arctium lappa
plant. In our previous study, we isolated one single bacterium capable of
bioconverting arctigenin, an aglycone of arctiin, to 3'-desmethylarctigenin (3'
DMAG) solely. However, to date, a specific bacterium capable of producing other
arctiin metabolites has not been reported. In this study, we isolated one single
bacterium, which we named Eggerthella sp. AUH-JLD49s, capable of bioconverting 3'
DMAG under anaerobic conditions. The metabolite of 3'-DMAG by strain AUH-JLD49s
was identified as 3'-desmethyl-4'-dehydroxyarctigenin (DMDH-AG) based on
electrospray ionization mass spectrometry (ESI-MS) and 1H and 13C nuclear
magnetic resonance spectroscopy. The bioconversion kinetics and bioconversion
capacity of strain AUH-JLD49s were investigated. In addition, the metabolite DMDH
AG showed an inhibitory effect on cell growth of human colon cancer cell line
HCT116 and human breast cancer cell line MDA-MB-231.
PMID- 28493690
TI - Chemically Propelled Molecules and Machines.
AB - Self-propelled, synthetic active matters that transduce chemical energy into
mechanical motion are examples of biomimetic nonequilibrium systems. They are of
great current interest, with potential applications in nanomachinery, nanoscale
assembly, fluidics, and chemical/biochemical sensing. Many of the physical
challenges associated with generating motility on the micro- and nanoscale have
recently been overcome, leading to the first generation of autonomous motors and
pumps on scales ranging from microns to nanometers. This perspective focuses on
catalytically powered motile systems, outlining major advances to date in
motor/pump design, propulsion mechanisms and directional control, and intermotor
communications leading to collective behavior. We conclude by discussing the
possible future directions, from the fundamental questions that remain to be
addressed to the design principles required for useful applications.
PMID- 28493689
TI - A Bis-calix[4]pyrrole Enzyme Mimic That Constrains Two Oxoanions in Close
Proximity.
AB - Herein we describe a large capsule-like bis-calix[4]pyrrole 1, which is able to
host concurrently two dihydrogen phosphate anions within a relatively large
internal cavity. Evidence for the concurrent, dual recognition of the
encapsulated anions came from 1H NMR and UV-vis spectroscopies and ITC titrations
carried out in CD2Cl2/CD3OD (9/1, v/v) or dichloroethane (DCE), as well as single
crystal X-ray diffraction analyses. Receptor 1 was also found to bind two
dianionic sulfate anions bridged by two water molecules in the solid state. The
resulting sulfate dimer was retained in DCE solution, as evidenced by
spectroscopic analyses. Finally, receptor 1 was found capable of accommodating
two trianionic pyrophosphate anions in the cavity. The present experimental
findings are supported by DFT calculations along with 1H NMR and UV-vis
spectroscopies, ITC studies, and single crystal X-ray diffraction analyses.
PMID- 28493691
TI - Surface Proton Transfer Promotes Four-Electron Oxygen Reduction on Gold
Nanocrystal Surfaces in Alkaline Solution.
AB - Four-electron oxygen reduction reaction (4e-ORR), a key pathway in energy
conversion, is preferred over the two-electron reduction pathway that falls short
in dissociating dioxygen molecules. Gold surfaces exhibit high sensitivity of the
ORR pathway to its atomic structures. A long-standing puzzle remains unsolved:
why the Au surfaces with {100} sub-facets were exceptionally capable to catalyze
the 4e-ORR in alkaline solution, though limited within a narrow potential window.
Herein we report the discovery of a dominant 4e-ORR over the whole potential
range on {310} surface of Au nanocrystal shaped as truncated ditetragonal prism
(TDP). In contrast, ORR pathways on single-crystalline facets of shaped
nanoparticles, including {111} on nano-octahedra and {100} on nanocubes, are
similar to their single-crystal counterparts. Combining our experimental results
with density functional theory calculations, we elucidate the key role of surface
proton transfers from co-adsorbed H2O molecules in activating the facet- and
potential-dependent 4e-ORR on Au in alkaline solutions. These results elucidate
how surface atomic structures determine the reaction pathways via bond scission
and formation among weakly adsorbed water and reaction intermediates. The new
insight helps in developing facet-specific nanocatalysts for various reactions.
PMID- 28493692
TI - Uptake Kinetics and Subcellular Compartmentalization Explain Lethal but Not
Sublethal Effects of Cadmium in Two Closely Related Amphipod Species.
AB - Eulimnogammarus cyaneus and Eulimnogammarus verrucosus, closely related amphipod
species endemic to Lake Baikal, differ with respect to body size (10- to 50-fold
lower fresh weights of E. cyaneus) and cellular stress response (CSR) capacity,
potentially causing species-related differences in uptake, internal
sequestration, and toxic sensitivity to waterborne cadmium (Cd). We found that,
compared to E. verrucosus, Cd uptake rates, related to a given exposure
concentration, were higher, and lethal concentrations (50%; LC50) were 2.3-fold
lower in E. cyaneus (4 weeks exposure; 6 degrees C). Upon exposures to species
specific subacutely toxic Cd concentrations (nominal LC1; E. cyaneus: 18 nM (2.0
MUg L-1); E. verrucosus: 115 nM (12.9 MUg L-1); 4 weeks exposure; 6 degrees C),
Cd amounts in metal sensitive tissue fractions (MSF), in relation to fresh
weight, were similar in both species (E. cyaneus: 0.25 +/- 0.06 MUg g-1; E.
verrucosus: 0.26 +/- 0.07 MUg g-1), whereas relative Cd amounts in the
biologically detoxified heat stable protein fraction were 35% higher in E.
cyaneus. Despite different potencies in detoxifying Cd, body size appears to
mainly explain species-related differences in Cd uptake and sensitivities. When
exposed to Cd at LC1 over 4 weeks, only E. verrucosus continuously showed 15-36%
reduced oxygen consumption rates indicating metabolic depression and pointing to
particular sensitivity of E. verrucosus to persisting low-level toxicant
pressure.
PMID- 28493693
TI - Development of Lennard-Jones and Buckingham Potentials for Lanthanoid Ions in
Water.
AB - New sets of Lennard-Jones and Buckingham potentials have been developed to be
used in classical molecular dynamics simulations of Ln3+-containing systems for
the whole lanthanoid series. The force-field parameters have been refined by
directly comparing the hydration structure obtained from the simulations with the
extended X-ray absorption fine structure (EXAFS) experimental data, in order to
reproduce Ln3+-water EXAFS experimentally inferred mean distances. Analysis of
the simulation results has shown that both Lennard-Jones and Buckingham
potentials are able to properly describe the radial distribution of water
molecules around the Ln3+ ions, the smooth decrease of the hydration number along
the lanthanoid series, as well as the geometry of the first-shell hydration
complex formed by Ln3+ ions in water. The newly optimized interaction potential
parameters can be used in conjunction with force fields available in the
literature to investigate the solvation properties of Ln3+ ions in different
disordered systems.
PMID- 28493694
TI - Community Vulnerability to Health Impacts of Wildland Fire Smoke Exposure.
AB - Identifying communities vulnerable to adverse health effects from exposure to
wildfire smoke may help prepare responses, increase the resilience to smoke and
improve public health outcomes during smoke days. We developed a Community Health
Vulnerability Index (CHVI) based on factors known to increase the risks of health
effects from air pollution and wildfire smoke exposures. These factors included
county prevalence rates for asthma in children and adults, chronic obstructive
pulmonary disease, hypertension, diabetes, obesity, percent of population 65
years of age and older, and indicators of socioeconomic status including poverty,
education, income and unemployment. Using air quality simulated for the period
between 2008 and 2012 over the continental U.S. we also characterized the
population size at risk with respect to the level and duration of exposure to
fire-originated fine particulate matter (fire-PM2.5) and CHVI. We estimate that
10% of the population (30.5 million) lived in the areas where the contribution of
fire-PM2.5 to annual average ambient PM2.5 was high (>1.5 MUg/m3) and that 10.3
million individuals experienced unhealthy air quality levels for more than 10
days due to smoke. Using CHVI we identified the most vulnerable counties and
determined that these communities experience more smoke exposures in comparison
to less vulnerable communities.
PMID- 28493695
TI - Unexpected Observation of the Dimroth Rearrangement in the Ribosylation of 4
Aminopyrimidines.
AB - A method for the preparation of 1-(N-ribofuranosyl)-6-imino-1,6-dihydropyrimidin
4-amines 3 or 4-(N-ribofuranosyl)-6-aminopyrimidines 4 via glycosylation of 4
aminopyrimidines 2 or 5 is described. Silylated 4-aminopyrimidines 2 or 5 upon
ribosylation with 1 provide products 3. When intermediates 3 contain a strongly
electron-withdrawing group, such as C(4)-Cl or C(5)-NO2, they rearrange to
products 4 in the presence of aqueous ammonia. A mechanism is proposed that
involves a ring-opening/ring-closing (Dimroth) rearrangement.
PMID- 28493696
TI - Impact of Conjugation and Hyperconjugation on the Radical Stability of Allylic
and Benzylic Systems: A Theoretical Study.
AB - Resonantly stabilized radicals are some of the most investigated chemical species
due to their preferential formation in a wide variety of chemical environments.
Density functional theory and post-Hartree-Fock calculations were utilized to
elucidate the chemical interactions that contribute to the stability of two
ubiquitous, resonantly stabilized radicals, allyl and benzyl radicals. The
relative stability of these radical species was quantified through bond
dissociation energies and relative rotational energy barriers, with a difference
of only 0.1 kcal/mol. To clarify and contextualize the energetic results, natural
bond orbitals were used to evaluate the atomic spin density distribution in the
given molecules. The benzyl radical was found to be ~3 kcal/mol less stable than
the allyl radical, which was attributed to the inability to efficiently
delocalize the spin on a phenyl unit, starkly contrary to general chemistry
knowledge. Increasing the degree of pi-conjugation and hyperconjugation was shown
to benefit allyl radicals to a greater degree than benzyl radicals, again due to
more efficient radical delocalization in allyl radicals. This work highlights
that more resonance structures do not always lead to a more stabilized radical
species, and provides fundamental knowledge about how conjugation and
hyperconjugation impact the stabilization of nonbonding electrons in these
systems.
PMID- 28493697
TI - Molecular Explanation for the Abnormal Flux of Material into a Hot Spot in Ester
Monolayers.
AB - Langmuir monolayers of certain surfactants show a negative derivative of the
surface pressure with respect to temperature. In these monolayers, a local
temperature gradient leads to local yielding of the solid phase to a kinetically
flowing liquid, so that the material flows toward the hotter regions that act as
sinks. The accumulation of material leads to the formation of nonequilibrium
multilamellar bubbles of different sizes. Here we investigate the molecular
factors leading to such a peculiar behavior. First, we identify the required
structural molecular moieties, and second we vary the composition of the subphase
in order to analyze its influence. We conclude that esters appear to be unique in
two key aspects: they form monolayers whose compression isotherms shift to lower
areas as the temperature increases, and thus collapse into a hot spot; and they
bind weakly to the aqueous subphase, i.e., water does not attach to the monolayer
at the molecular level, but only supports it. Molecular simulations for a
selected system confirm and help explain the observed behavior: surfactant
molecules form a weak hydrogen bonding network, which is disrupted upon heating,
and also the molecular tilting changes with temperature, leading to changes in
the film density.
PMID- 28493699
TI - Electrochemical Oxidation of Phenolic Compounds at Boron-Doped Diamond Anodes:
Structure-Reactivity Relationships.
AB - Electrochemical oxidation of phenolic compounds using boron-doped diamond (BDD)
anodes has been shown as an effective approach to remove these contaminants from
water. However, the understanding of the reaction mechanisms of substituted
phenolic compounds at the BDD anode remains incomplete. In the present work, we
investigated the electrochemical oxidation of 12 representative phenolic
compounds (with varied substitution groups (e.g., -CH3, -OCH3, -NH2, -Cl, -OH,
COOH, -NO2, -CHO) and positions (-ortho, -meta, and -para)) at the BDD anode. Our
analysis shows that unlike previous studies the two parameters, the Hammett
constants of the substituents and the highest atomic charge on the aromatic ring,
fail to adequately describe the reaction rate change when the chemical structures
become complicated (i.e., with increased steric effects). Instead, a quantitative
structure-property relationship (QSPR) was established with 26 molecular
descriptors and using a partial least-squares regression approach. The QSPR
analysis shows that the energy gap between the lowest unoccupied molecular
orbital and the highest occupied molecular orbital, ELUMO - EHOMO, which reflects
the chemical stability of a molecule, is the predominant molecular descriptor
determining the reaction rate constant. Furthermore, the predicated rate
constants agree well with the observed ones. The findings are consistent with
previous studies of SnO2 anodes, suggesting that chemical structural parameters
such as the molecular orbital energies are critical to consider when elucidating
and predicating the electrochemical reactivity of phenolic compounds at these
nonactive anodes.
PMID- 28493700
TI - Effect of Fluorination on the Competition of Halogen Bonding and Hydrogen
Bonding: Complexes of Fluoroiodomethane with Dimethyl Ether and Trimethylamine.
AB - To further rationalize the competition between halogen and hydrogen bonding, a
combined experimental and theoretical study on the weakly bound molecular
complexes formed between the combined halogen bond/hydrogen bond donor
fluoroiodomethane and the Lewis bases dimethyl ether and trimethylamine (in
standard and fully deuterated form) is presented. The experimental data are
obtained by recording infrared and Raman spectra of mixtures of the compounds in
liquid krypton, at temperatures between 120 and 156 K. The experiments are
supported by ab initio calculations at the MP2/aug-cc-pVDZ-PP level, statistical
thermodynamics and Monte Carlo free energy perturbation calculations. For the
mixtures containing fluoroiodomethane and dimethyl ether a hydrogen-bonded
complex with an experimental complexation enthalpy of -7.0(2) kJ mol-1 is
identified. Only a single weak spectral feature is observed which can be
tentatively assigned to the halogen-bonded complex. For the mixtures involving
trimethylamine, both halogen- and hydrogen-bonded complexes are observed, the
experimental complexation enthalpies being -12.5(1) and -9.6(2) kJ mol-1
respectively. To evaluate the influence of fluorination on the competition
between halogen and hydrogen bonding, the results obtained for fluoroiodomethane
are compared with those of a previous study involving difluoroiodomethane.
PMID- 28493698
TI - 4-Methyl-6,7-dihydro-4H-triazolo[4,5-c]pyridine-Based P2X7 Receptor Antagonists:
Optimization of Pharmacokinetic Properties Leading to the Identification of a
Clinical Candidate.
AB - The synthesis and preclinical characterization of novel 4-(R)-methyl-6,7-dihydro
4H-triazolo[4,5-c]pyridines that are potent and selective brain penetrant P2X7
antagonists are described. Optimization efforts based on previously disclosed
unsubstituted 6,7-dihydro-4H-triazolo[4,5-c]pyridines, methyl substituted 5,6,7,8
tetrahydro[1,2,4]triazolo[4,3-a]pyrazines, and several other series lead to the
identification of a series of 4-(R)-methyl-6,7-dihydro-4H-triazolo[4,5
c]pyridines that are selective P2X7 antagonists with potency at the rodent and
human P2X7 ion channels. These novel P2X7 antagonists have suitable
physicochemical properties, and several analogs have an excellent pharmacokinetic
profile, good partitioning into the CNS and show robust in vivo target engagement
after oral dosing. Improvements in metabolic stability led to the identification
of JNJ-54175446 (14) as a candidate for clinical development. The drug discovery
efforts and strategies that resulted in the identification of the clinical
candidate are described herein.
PMID- 28493702
TI - Copper-Catalyzed Functionalizations of C60 with Amino Alcohols.
AB - CuI-catalyzed diverse functionalizations of C60 with amino alcohols with aerobic
oxygen as the sole oxidant have been explored. For 2-/3-amino alcohols, an
aminooxygenation reaction occurs to generate fulleromorpholine and
fullerooxazepane derivatives. When a tethered furan ring exists, a further
intramolecular [4 + 2] reaction with the neighboring double bond occurs to
furnish the cis-1 products. In the case of 4-/5-amino alcohols, methanofullerenes
linking with cyclic amides are obtained through cyclic enamine intermediates.
PMID- 28493703
TI - Theoretical Study of the BF3-Promoted Rearrangement of Oxiranyl N
Methyliminodiacetic Acid Boronates.
AB - The mechanism of the rearrangement of oxiranyl N-methyliminodiacetyl (MIDA)
boronates in dicholoromethane has been extensively investigated with density
functional theory. Several reaction pathways were examined. Our results revealed
that the most-favorable mechanisms for the BF3-promoted rearrangement of 2-phenyl
oxiranyl MIDA boronate (1) and 1-phenyl oxiranyl MIDA boronate (24) comprise two
steps: ring opening of the epoxide to a carbocation intermediate followed by
migration of a MIDA-boryl group (for the reaction of 1) and hydrogen (for the
reaction of 24), to give the same BF3-coordinated alpha-boryl aldehyde in both
cases. The first step of the ring opening of the epoxide is the rate-determining
step of these reactions. In the rearrangement step for the reaction of 1, the
MIDA-boryl group migrates easily, probably because of its electron-rich sp3
hybridized boron center. For 24, the most-favorable pathway involves a rare boryl
substituted carbocation. The course of these reactions is mainly controlled by
electronic effects, although steric effects are also significant. The higher
energy barrier calculated for the unsubstituted oxiranyl MIDA boronate (31)
explains the lack of reactivity in the studied BF3-promoted rearrangement.
PMID- 28493701
TI - Substituted 2-Acylaminocycloalkylthiophene-3-carboxylic Acid Arylamides as
Inhibitors of the Calcium-Activated Chloride Channel Transmembrane Protein 16A
(TMEM16A).
AB - Transmembrane protein 16A (TMEM16A), also called anoctamin 1 (ANO1), is a calcium
activated chloride channel expressed widely mammalian cells, including epithelia,
vascular smooth muscle tissue, electrically excitable cells, and some tumors.
TMEM16A inhibitors have been proposed for treatment of disorders of epithelial
fluid and mucus secretion, hypertension, asthma, and possibly cancer. Herein we
report, by screening, the discovery of 2-acylaminocycloalkylthiophene-3
carboxylic acid arylamides (AACTs) as inhibitors of TMEM16A and analysis of 48
synthesized analogs (10ab-10bw) of the original AACT compound (10aa). Structure
activity studies indicated the importance of benzene substituted as 2- or 4
methyl, or 4-fluoro, and defined the significance of thiophene substituents and
size of the cycloalkylthiophene core. The most potent compound (10bm), which
contains an unusual bromodifluoroacetamide at the thiophene 2-position, had IC50
of ~30 nM, ~3.6-fold more potent than the most potent previously reported TMEM16A
inhibitor 4 (Ani9), and >10-fold improved metabolic stability. Direct and
reversible inhibition of TMEM16A by 10bm was demonstrated by patch-clamp
analysis. AACTs may be useful as pharmacological tools to study TMEM16A function
and as potential drug development candidates.
PMID- 28493704
TI - Chemoselective Reduction of Azlactones Using Schwartz's Reagent.
AB - Highly chemoselective addition of Schwartz's reagent to widely available
azlactones is described. This method allows the preparation of challenged
functionalized alpha-amino aldehydes, in good to high isolated yields at room
temperature, after only 2 min reaction. The presence of sensitive functionalities
or electronic factors does not compromise the potential of the method. The use of
an excess of the reducing reagent gave a very functionalized allylic alcohol
derivative in 86% yield.
PMID- 28493706
TI - Correction to Multilayered Modeling of Particulate Matter Removal by a Growing
Forest over Time, From Plant Surface Deposition to Washoff via Rainfall.
PMID- 28493707
TI - General Physical Description of the Behavior of Oppositely Charged
Polyelectrolyte/Surfactant Mixtures at the Air/Water Interface.
AB - This work reports a unifying general physical description of the behavior of
oppositely charged polyelectrolyte/surfactant mixtures at the air/water interface
in terms of equilibrium vs nonequilibrium extremes. The
poly(diallyldimethylammonium chloride)/sodium dodecyl sulfate system with added
NaCl at two different bulk polyelectrolyte concentrations and the poly(sodium
styrenesulfonate)/dodecyltrimethylammonium bromide system have been
systematically examined using a variety of bulk and surface techniques.
Similarities in the general behavior are observed for all the investigated
systems. Following the slow precipitation of aggregates in the equilibrium two
phase region, which can take several days or even weeks, depletion of surface
active material can result in a surface tension peak. The limiting time scale in
the equilibration of the samples is discussed in terms of a balance between those
of aggregate growth and settling. Bulk aggregates may spontaneously dissociate
and spread material in the form of a kinetically trapped film if they interact
with the interface, and a low surface tension then results out of equilibrium
conditions. These interactions can occur prior to bulk equilibration while there
remains a suspension of aggregates that can diffuse to the interface and
following bulk equilibration if the settled precipitate is disturbed. Two clear
differences in the behavior of the systems are the position in the isotherm of
the surface tension peak and the time it takes to evolve. These features are both
rationalized in terms of the nature of the bulk binding interactions.
PMID- 28493705
TI - Quantification of Hemoglobin and White Blood Cell DNA Adducts of the Tobacco
Carcinogens 2-Amino-9H-pyrido[2,3-b]indole and 4-Aminobiphenyl Formed in Humans
by Nanoflow Liquid Chromatography/Ion Trap Multistage Mass Spectrometry.
AB - Aromatic amines covalently bound to hemoglobin (Hb) as sulfinamide adducts at the
cysteine 93 residue of the Hb beta chain have served as biomarkers to assess
exposure to this class of human carcinogens for the past 30 years. In this study,
we report that 2-amino-9H-pyrido[2,3-b]indole (AalphaC), an abundant carcinogenic
heterocyclic aromatic amine formed in tobacco smoke and charred cooked meats,
also reacts with Hb to form a sulfinamide adduct. A novel nanoflow liquid
chromatography/ion trap multistage mass spectrometry (nanoLC-IT/MS3) method was
established to assess exposure to AalphaC and the tobacco-associated bladder
carcinogen 4-aminobiphenyl (4-ABP) through their Hb sulfinamide adducts.
Following mild acid hydrolysis of Hb in vitro, the liberated AalphaC and 4-ABP
were derivatized with acetic anhydride to form the N-acetylated amines, which
were measured by nanoLC-IT/MS3. The limits of quantification (LOQ) for AalphaC-
and 4-ABP-Hb sulfinamide adducts were <=7.1 pg/g Hb. In a pilot study, the mean
level of Hb sulfinamide adducts of AalphaC and 4-ABP were, respectively, 3.4-fold
and 4.8-fold higher in smokers (>20 cigarettes/day) than nonsmokers. In contrast,
the major DNA adducts of 4-ABP, N-(2'-deoxyguanosin-8-yl)-4-aminobiphenyl, and
AalphaC, N-(2'-deoxyguanosin-8-yl)-2-amino-9H-pyrido[2,3-b]indole, were below the
LOQ (3 adducts per 109 bases) in white blood cell (WBC) DNA of smokers and
nonsmokers. These findings reaffirm that tobacco smoke is a major source of
exposure to AalphaC. Hb sulfinamide adducts are suitable biomarkers to biomonitor
4-ABP and AalphaC; however, neither carcinogen binds to DNA in WBC, even in heavy
smokers, at levels sufficient for biomonitoring.
PMID- 28493708
TI - Discrimination of Diverse Coherences Allows Identification of Electronic
Transitions of a Molecular Nanoring.
AB - The role of quantum coherence in photochemical functions of molecular systems
such as photosynthetic complexes is a broadly debated topic. Coexistence and
intermixing of electronic and vibrational coherences has been proposed to be
responsible for the observed long-lived coherences and high energy transfer
efficiency. However, clear experimental evidence of coherences with different
origins operating at the same time has been elusive. In this work,
multidimensional spectra obtained from a six-porphyrin nanoring system are
analyzed in detail with support from theoretical modeling. We uncover a great
diversity of separable electronic, vibrational, and mixed coherences and show
their cooperation in shaping the spectroscopic response. The results permit
direct assignment of electronic and vibronic states and characterization of the
excitation dynamics. The clear disentanglement of coherences in molecules with
extended pi-conjugation opens up new avenues for exploring coherent phenomena and
understanding their importance for the function of complex systems.
PMID- 28493709
TI - Rh/DuanPhos-Catalyzed Asymmetric Hydrogenation of beta-Acetylamino Vinylsulfides:
An Approach to Chiral beta-Acetylamino Sulfides.
AB - Rh/DuanPhos-catalyzed asymmetric hydrogenation of challenging beta-acetylamino
vinylsulfides has been developed, affording chiral beta-acetylamino sulfides with
high yields and excellent ee's (up to 99% ee). This novel methodology provides an
efficient and concise synthetic route to chiral beta-acetylamino sulfides. The
potential utility of this protocol in the synthesis of Apremilast has also been
disclosed.
PMID- 28493711
TI - Structural Evolution of Sub-10 nm Octahedral Platinum-Nickel Bimetallic
Nanocrystals.
AB - Octahedral Pt alloy nanocrystals (NCs) have shown excellent activities as
electrocatalysts toward oxygen reduction reaction (ORR). As the activity and
stability of NCs are highly dependent on their structure and the elemental
distribution, it is of great importance to understand the formation mechanism of
octahedral NCs and to rationally synthesize shape-controlled alloy catalysts with
optimized ORR activity and stability. However, the factors controlling the
structural and compositional evolution during the synthesis have not been well
understood yet. Here, we systematically investigated the structure and
composition evolution pathways of Pt-Ni octahedra synthesized with the assistance
of W(CO)6 and revealed a unique core-shell structure consisting of a Pt core and
a Pt-Ni alloy shell. Below 140 degrees C, sphere-like pure Pt NCs with the
diameter of 3-4 nm first nucleated, followed by the isotropic growth of Pt-Ni
alloy on the seeds at temperatures between 170 and 230 degrees C forming Pt@Pt
Ni core-shell octahedra with {111} facets. Owing to its unique structure, the
Pt@Pt-Ni octahedra show an unparalleled stability during potential cycling, that
is, no activity drop after 10 000 cycles between 0.6 and 1.0 V. This work
proposes the Pt@Pt-Ni octahedra as a high profile electrocatalyst for ORR and
reveals the structural and composition evolution pathways of Pt-based bimetallic
NCs.
PMID- 28493710
TI - Nuclear Localizing Peptide-Conjugated, Redox-Sensitive Polymersomes for
Delivering Curcumin and Doxorubicin to Pancreatic Cancer Microtumors.
AB - Improving the therapeutic index of anticancer agents is an enormous challenge.
Targeting decreases the side effects of the therapeutic agents by delivering the
drugs to the intended destination. Nanocarriers containing the nuclear localizing
peptide sequences (NLS) translocate to the cell nuclei. However, the nuclear
localization peptides are nonselective and cannot distinguish the malignant cells
from the healthy counterparts. In this study, we designed a "masked" NLS peptide
which is activated only in the presence of overexpressed matrix metalloproteinase
7 (MMP-7) enzyme in the pancreatic cancer microenvironment. This peptide is
conjugated to the surface of redox responsive polymersomes to deliver doxorubicin
and curcumin to the pancreatic cancer cell nucleus. We have tested the
formulation in both two- and three-dimensional cultures of pancreatic cancer and
normal cells. Our studies revealed that the drug-encapsulated polymeric vesicles
are significantly more toxic toward the cancer cells (shrinking the spheroids up
to 49%) compared to the normal cells (shrinking the spheroids up to 24%). This
study can lead to the development of other organelle targeted drug delivery
systems for various human malignancies.
PMID- 28493712
TI - Stimulus-Responsive Degradable Polylactide-Based Block Copolymer Nanoassemblies
for Controlled/Enhanced Drug Delivery.
AB - Polylactide (PLA) is biocompatible and FDA-approved for clinical use and thus has
been a choice of the materials valuable for extensive applications in biomedical
fields. However, conventionally designed PLA-based amphiphilic block copolymer
(ABP) nanoassemblies exhibit slow and uncontrolled release of encapsulated drugs
because of the slow biodegradation of hydrophobic PLA in physiological
conditions. To improve potentials for clinical use and commercialization of
conventional PLA-based nanoassemblies, stimulus-responsive degradation (SRD)
platform has been introduced into the design of PLA-based nanoassemblies for
enhanced/controlled release of encapsulated drugs. This review summarizes recent
strategies that allow for the development of PLA-based ABPs and their self
assembled nanostructures exhibiting SRD-induced enhanced drug release. The review
focuses on the design, synthesis, and evaluation of the nanoassemblies as
intracellular drug delivery nanocarriers for cancer therapy. Further, the outlook
is briefly discussed on the important aspects for the current and future
development of more effective SRD PLA-based nanoassemblies toward tumor-targeting
intracellular drug delivery.
PMID- 28493714
TI - Relativistic Polarizable Embedding.
AB - Most chemistry, including chemistry where relativistic effects are important,
occurs in an environment, and in many cases, this environment has a significant
effect on the chemistry. In nonrelativistic quantum chemistry, a lot of progress
has been achieved with respect to including environments such as a solvent or
protein in the calculations, and now is the time to extend the possibilities for
also doing this in relativistic quantum chemistry. The polarizable embedding (PE)
model efficiently incorporates electrostatic effects of the environment by
describing it as a collection of localized electric multipoles and
polarizabilities obtained through quantum chemical calculations. In this article,
we present the theory and implementation of four- and exact two-component
Hamiltonians within a PE framework. We denote the methods the PE-4c-DFT and PE
X2C-DFT models. The models include a linear response formalism to calculate time
dependent (TD) properties: PE-TD-4c-DFT and PE-TD-X2C-DFT. With this first
implementation, we calculate the PE-TD-4c-PBE0 excitation energies of the TcO4-
and ReO4- ions in an explicit water solvent. This initial investigation focuses
on the relative size of relativistic and solvent contributions to the excitation
energies. The solvent effect is divided into an indirect solvent effect due to
the structural perturbation of the XO4- ion and a direct electrostatic effect.
The relativistic effects as well as both types of solvent effects are found to
contribute to a shift in the excitation energies, but they do so to different
extents depending on the ion and the electronic transition in question.
PMID- 28493715
TI - Recent Trends in Quantum Chemical Modeling of Enzymatic Reactions.
AB - The quantum chemical cluster approach is a powerful method for investigating
enzymatic reactions. Over the past two decades, a large number of highly diverse
systems have been studied and a great wealth of mechanistic insight has been
developed using this technique. This Perspective reviews the current status of
the methodology. The latest technical developments are highlighted, and
challenges are discussed. Some recent applications are presented to illustrate
the capabilities and progress of this approach, and likely future directions are
outlined.
PMID- 28493716
TI - Bifenthrin Causes Toxicity in Urban Stormwater Wetlands: Field and Laboratory
Assessment Using Austrochiltonia (Amphipoda).
AB - Stormwater wetlands are engineered to accumulate sediment and pollutants from
stormwater and provide environmental value to urban environments. Therefore,
contaminated sediment risks causing toxicity to aquatic fauna. This research
identifies contaminants of concern in urban wetland sediments by assessing
sediment toxicity using the amphipod Austrochiltonia subtenuis. Sediments from 98
wetlands were analyzed for contaminants, and laboratory bioassays were performed
with A. subtenuis. Wild Austrochiltonia spp. were also collected from wetlands to
assess field populations. Random forest modeling was used to identify the most
important variables predicting survival, growth, and field absence of
Austrochiltonia spp. Bifenthrin was the most frequently detected pesticide and
also the most important predictor of Austrochiltonia spp. responses. Copper,
permethrin, chromium, triclosan, and lead were also important. The median lethal
effect concentration (LC50) of bifenthrin to laboratory-based A. subtenuis (1.09
(+/-0.08) MUg/gOC) exposed to wetland sediments was supported by a bifenthrin
spiked sediment experiment, indicating A. subtenuis is a suitable test species.
Furthermore, Austrochiltonia spp. were absent from all sites that exceeded the
calculated bifenthrin LC50, demonstrating the impact of this contaminant on wild
populations. This research demonstrates the sensitivity of Austrochiltonia spp.
to urban sediment contamination and identifies bifenthrin as a contaminant of
concern in urban wetlands.
PMID- 28493713
TI - Cetuximab Prevents Methotrexate-Induced Cytotoxicity in Vitro through Epidermal
Growth Factor Dependent Regulation of Renal Drug Transporters.
AB - The combination of methotrexate with epidermal growth factor receptor (EGFR)
recombinant antibody, cetuximab, is currently being investigated in treatment of
head and neck carcinoma. As methotrexate is cleared by renal excretion, we
studied the effect of cetuximab on renal methotrexate handling. We used human
conditionally immortalized proximal tubule epithelial cells overexpressing either
organic anion transporter 1 or 3 (ciPTEC-OAT1/ciPTEC-OAT3) to examine OAT1 and
OAT3, and the efflux pumps breast cancer resistance protein (BCRP), multidrug
resistance protein 4 (MRP4), and P-glycoprotein (P-gp) in methotrexate handling
upon EGF or cetuximab treatment. Protein kinase microarrays and knowledge-based
pathway analysis were used to predict EGFR-mediated transporter regulation.
Cytotoxic effects of methotrexate were evaluated using the dimethylthiazol
bromide (MTT) viability assay. Methotrexate inhibited OAT-mediated fluorescein
uptake and decreased efflux of Hoechst33342 and glutathione-methylfluorescein (GS
MF), which suggested involvement of OAT1/3, BCRP, and MRP4 in transepithelial
transport, respectively. Cetuximab reversed the EGF-increased expression of OAT1
and BCRP as well as their membrane expressions and transport activities, while
MRP4 and P-gp were increased. Pathway analysis predicted cetuximab-induced
modulation of PKC and PI3K pathways downstream EGFR/ERBB2/PLCg. Pharmacological
inhibition of ERK decreased expression of OAT1 and BCRP, while P-gp and MRP4 were
increased. AKT inhibition reduced all transporters. Exposure to methotrexate for
24 h led to a decreased viability, an effect that was reversed by cetuximab. In
conclusion, cetuximab downregulates OAT1 and BCRP while upregulating P-gp and
MRP4 through an EGFR-mediated regulation of PI3K-AKT and MAPKK-ERK pathways.
Consequently, cetuximab attenuates methotrexate-induced cytotoxicity, which opens
possibilities for further research into nephroprotective comedication therapies.
PMID- 28493717
TI - [2 + 2]-type Reaction of Metal-Metal sigma-Bond with Fullerene Forming an eta1
C60 Metal Complex: Mechanistic Details of Formation Reaction and Prediction of a
New eta1-C60 Metal Complex.
AB - C60[CpRu(CO)2]2 is only one transition-metal fullerene complex with pure eta1
coordinated bonds, which was recently synthesized through the reaction between
dinuclear Ru complex [CpRu(CO)2]2 and C60. Though new properties can be expected
in the eta1-coordinated metal-fullerene complex, its characteristic features are
unclear, and the [2 + 2]-type formation reaction is very slow with a very small
yield. A density functional theory study discloses that the eta1-coordinated bond
is formed by a large overlap between the Ru dsigma orbital and C psigma one
involved in the lowest unoccupied molecular orbital (LUMO) (pi*) of C60 unlike
the well-known eta2-coordinated metal-fullerene complex which has a pi-type
coordinate bond with metal dpi orbital. The binding energy per one Ru-C bond is
much smaller than those of eta2-coordinated Pt(PMe3)2(C60) and IrH(CO)(PH3)2(C60)
because the Ru d orbital exists at low energy. The formation reaction occurs via
Ru-Ru bond cleavage on the C60 surface followed by a direction change of
CpRu(CO)2 to afford C60[CpRu(CO)2]2 in a stepwise manner via two asymmetrical
transition states to avoid a symmetry-forbidden character. The calculated Gibbs
activation energy (DeltaG degrees ?) is very large and the Gibbs reaction energy
(DeltaG degrees ) is moderately negative, which are consistent with a very slow
reaction rate and very small yield. The charge transfer from CpRu(CO)2 to
fullerene CT(Ru -> C60) is important in the reaction, but it is small due to the
presence of the Ru d orbital at low energy, which is the reason for the large
DeltaG degrees ? and moderately negative DeltaG degrees . The use of Li+@C60 is
theoretically predicted to accelerate the reaction and increase the yield of
Li+@C60[CpRu(CO)2]2, because the CT(Ru -> C60) is enhanced by the low energy LUMO
of Li+@C60. It is also predicted that Li+@C60[Re(CO)4(PMe3)]2 is a next promising
target for the synthesis of the eta1-coordinated metal-fullerene complex, but
syntheses of C60[Co(CO)4]2, C60[Re(CO)5]2, Li+@C60[Co(CO)4]2, and
Li+@C60[Re(CO)5]2 are difficult. The use of nonpolar solvent is another important
factor for the synthesis of the eta1-coordinated metal complex with Li+@C60.
PMID- 28493718
TI - Tamarixetin 3-O-beta-d-Glucopyranoside from Azadirachta indica Leaves:
Gastroprotective Role through Inhibition of Matrix Metalloproteinase-9 Activity
in Mice.
AB - Neem (Azadirachta indica) is a well-known medicinal and insecticidal plant.
Although previous studies have reported the antiulcer activity of neem leaf
extract, the lead compound is still unidentified. The present study reports
tamarixetin 3-O-beta-d-glucopyranoside (1) from a methanol extract of neem leaves
and its gastroprotective activity in an animal model. Compound 1 showed
significant protection against indomethacin-induced gastric ulceration in mice in
a dose-dependent manner. Moreover, ex vivo and circular dichroism studies
confirmed that 1 inhibited the enzyme matrix metalloproteinase-9 (MMP-9) activity
with an IC50 value of ca. 50 MUM. Molecular docking and dynamics showed the
binding of 1 into the pocket of the active site of MMP-9, forming a coordination
complex with the catalytic zinc, thus leading to inhibition of MMP-9 activity.
PMID- 28493719
TI - Theoretical Study on the Open-Shell Singlet Nature and the Second
Hyperpolarizabilities of Corannulene Derivatives with Two Phenoxyl Radicals.
AB - Using the spin-unrestricted density functional theory method, we investigate the
interplay between the diradical character y and second hyperpolarizabilities
gamma (the third-order nonlinear optical (NLO) properties at the molecular scale)
of corannulene derivatives with two phenoxyl radicals. This molecule in the
singlet state exhibits intermediate y and thus displays a significantly larger
gamma value than the triplet state and the closed-shell bis-phenol analogue. We
also examine the planar molecules involving a coronene moiety in place of the
curved corannulene. The intermediate y and large gamma values of the corannulene
systems are found to originate not from their curved skeleton but from the
equilibrium between benzenoid/quinoid resonance forms due to delocalization of
the radical electrons of the terminal phenoxyl rings. The longitudinal gamma
value of the singlet state is found to be comparable to that of s-indaceno[1,2,3
cd;5,6,7-c'd']diphenalene, which is known to be one of the organic molecules with
the largest two-photon absorption cross section in this size of pure
hydrocarbons. The present system is thus expected to be a promising candidate for
highly efficient open-shell NLO molecules.
PMID- 28493720
TI - Tandem Catalysis for CO2 Hydrogenation to C2-C4 Hydrocarbons.
AB - Conversion of carbon dioxide to C2-C4 hydrocarbons is a major pursuit in clean
energy research. Despite tremendous efforts, the lack of well-defined catalysts
in which the spatial arrangement of interfaces is precisely controlled hinders
the development of more efficient catalysts and in-depth understanding of
reaction mechanisms. Herein, we utilized the strategy of tandem catalysis to
develop a well-defined nanostructured catalyst CeO2-Pt@mSiO2-Co for converting
CO2 to C2-C4 hydrocarbons using two metal-oxide interfaces. C2-C4 hydrocarbons
are found to be produced with high (60%) selectivity, which is speculated to be
the result of the two-step tandem process uniquely allowed by this catalyst.
Namely, the Pt/CeO2 interface converts CO2 and H2 to CO, and on the neighboring
Co/mSiO2 interface yields C2-C4 hydrocarbons through a subsequent Fischer-Tropsch
process. In addition, the catalysts show no obvious deactivation over 40 h. The
successful production of C2-C4 hydrocarbons via a tandem process on a rationally
designed, structurally well-defined catalyst demonstrates the power of
sophisticated structure control in designing nanostructured catalysts for
multiple-step chemical conversions.
PMID- 28493721
TI - Effects of Hydrotropic Salt on the Nanoscopic Dynamics of DTAB Micelles.
AB - Effects of a hydrotropic salt, sodium salicylate (NaSal), on the dynamic behavior
of cationic dodecyltrimethylammonium bromide (DTAB) micelles as studied using
dynamic light scattering (DLS) and quasielastic neutron scattering (QENS)
techniques are reported here. DLS study showed that the addition of NaSal leads
to a decrease in the apparent diffusion coefficient of the whole micelle
indicating micellar growth. QENS data analysis suggested that observed dynamics
involves two distinct motions, lateral motion of the surfactant over the curved
micellar surface and localized segmental motion of the surfactant. It is found
that the addition of NaSal slows down the lateral motion of DTAB while the
localized segmental motion of the DTAB chain is not affected much. An atomistic
molecular dynamics (MD) simulation was performed to gain further insight into the
underlying phenomena. MD simulation results are found to be consistent with the
experimental observations. MD simulation revealed that location of the salicylate
ions on the micellar surface and their strong electrostatic association with
their oppositely charged surfactant headgroup are the major factors in slowing
down the lateral motion of the DTAB molecule. In the present work, a quantitative
description of the effects of NaSal on the nanoscopic dynamics of DTAB micelles
and its correlation with the microstructure of the micelle is provided.
PMID- 28493722
TI - Synthesis of 4-Halo-3(2H)-furanones Using Intramolecular Cyclization of Sulfonium
Salts.
AB - A simple and efficient synthesis of 4-halo-3(2H)-furanones by halogenative
intramolecular cyclization of sulfonium salts is described, which can expedite
the production of a variety of 4-bromo- or 4-iodo-3(2H)-furanones, useful
synthetic building blocks, in good to high yield under mild conditions.
PMID- 28493723
TI - Influence of Conventional Surfactants on the Self-Assembly of a Bola Type
Amphiphilic Peptide.
AB - Structural and morphological regulation is a distinctly important topic in
peptide self-assembly, and is also regarded as the fundamental point in peptide
based biomaterials development. In this paper, we showed that adding anionic
surfactant SDS to a bola amphiphilic peptide KI4K could result in the
reconstruction of beta-sheet secondary structure besides the changes in self
assembly morphologies from nanotubes to helical ribbons, nanofibers, or straight
nanotapes according to the negatively stained transmission electron microscopy,
atomic force microscopy, circular dichroism spectroscopy, and Fourier transform
infrared spectroscopy results. The inducing effect of SDS was observed at both
above and below its CMC but with different transformation rates. Through
comparison to other surfactants, including CTAB, C12EO4, and AOT, we proposed
that the transitions of KI4K self-assemblies induced by anionic surfactants could
be mainly attributed to the effect of hydrophobic interaction and electrostatic
attraction between surfactants and peptide molecules. Rheological property
measurement and dye adsorption experiments were also carried out to evaluate the
properties of hydrogels formed by the peptide/surfactant hybrids. The samples
formed self-supporting hydrogels at proper SDS or AOT concentrations, and the
charges of hydrogel could be regulated by peptide to surfactant ratio.
PMID- 28493724
TI - Tuning the Viscoelasticity of Peptide Vesicles by Adjusting Hydrophobic Helical
Blocks Comprising Amphiphilic Polypeptides.
AB - Amphiphilic block polypeptides of poly(sarcosine)-b-(l-Val-Aib)6 and
poly(sarcosine)-b-(l-Leu-Aib)6 and their stereoisomers were self-assembled in
water. Three kinds of binary systems of poly(sarcosine)-b-(l-Leu-Aib)6 with
poly(sarcosine)-b-poly(d-Leu-Aib)6, poly(sarcosine)-b-poly(l-Val-Aib)6, or
poly(sarcosine)-b-(d-Val-Aib)6 generated vesicles of ca. 200 nm diameter. The
viscoelasticity of the vesicle membranes was evaluated by the nanoindentation
method using AFM in water. The elasticity of the poly(sarcosine)-b-(l-Leu
Aib)6/poly(sarcosine)-b-poly(d-Leu-Aib)6 vesicle was 11-fold higher than that of
the egg yolk liposome but decreased in combinations of the Leu- and Val-based
amphiphilic polypeptides. The membrane elasticity is found to be adjustable by a
suitable combination of helical blocks in terms of stereocomplex formation and
the interdigitation of side chains among helices in the molecular assemblies.
PMID- 28493725
TI - Questionnaire and behavioral task measures of impulsivity are differentially
associated with body mass index: A comprehensive meta-analysis.
AB - Although impulsivity has been implicated in the development and maintenance of
obesity, evidence linking impulsivity to obesity has been mixed. These mixed
findings may be related to differences in the type of impulsivity measures used
and the varied domains of impulsivity assessed by each measure. The present meta
analysis aimed to examine the impact of measurement selection on the relationship
between impulsivity and body mass index (BMI). A total of 142 articles met
inclusion criteria and were comprised of 315,818 participants. Effect sizes
consisted of Fisher's z-transformed correlation coefficients, which were weighted
by the inverse variance to establish the grand mean estimate of the relationship
between impulsivity and BMI. Overall weighted mean effect sizes also were
computed for each type and domain of impulsivity measure. Moderator analyses were
conducted using a mixed-effects approach to determine if the relationship between
impulsivity and BMI varied between the types of impulsivity measures used. On
average, participants were 32.25 (SD = 12.41) years of age, with a BMI of 26.63
(SD = 5.73) kg/m2. The overall relationship between impulsivity and BMI was small
but significant (r = .07). Behavioral task measures of impulsivity produced
significantly larger effect sizes (r = .10) than did questionnaire measures of
impulsivity (r = .05). Domains of impulsivity that assessed disinhibited
behaviors (r = .10), attentional deficits (r = .11), impulsive decision-making (r
= .10), and cognitive inflexibility (r = .17) produced significant effect sizes.
These meta-analytic findings demonstrate that impulsivity is positively
associated with BMI and further document that this association varies by the type
of impulsivity measure used and the domain of impulsivity assessed. (PsycINFO
Database Record
PMID- 28493726
TI - Anticipatory coarticulation and the minimal planning unit of speech.
AB - One of the most persistent arguments against the segment as the minimal planning
unit is that the seemingly ubiquitous, thus, presumed obligatory, nature of
anticipatory coarticulation (AC) effects favors the syllable or a larger unit. By
contrast, we present the results of 3 experiments showing that AC is not
ubiquitous, but graded and variable based on (a) phonological availability and
(b) the specific criterion to initiate articulation adopted by a speaker. We
further argue that phonological encoding is parallel. These results point to (a)
the segment, and not the syllable, as the minimal planning unit and (b) a
flexible planning scope. Implications with respect to the current formulation of
AC regarding phonological availability and the minimal unit of speech
articulation are discussed. (PsycINFO Database Record
PMID- 28493727
TI - Military sexual trauma is associated with eating disorders, while combat exposure
is not.
AB - OBJECTIVE: There are strong associations among trauma and eating disorders.
However, while trauma and eating disorders are more common among veterans than
other populations, there is little information on how military-specific stressors
affect eating disorder risk. This study's objective was to determine whether
military sexual trauma and combat exposure were independent predictors of eating
disorders among women veterans, a high-risk group. METHOD: Participants were
women age 18-70, using VA medical center services, without psychotic disorders or
suicidal ideation (N = 407). We estimated a cross-sectional logistic regression
model to predict eating disorders (anorexia, bulimia, binge eating disorder) as a
function of military sexual trauma and combat exposure, adjusting for demographic
variables. RESULTS: Sixty-six percent of participants reported military sexual
trauma, 32% reported combat exposure, and 15% met eating disorder criteria. Mean
age was 49 years (SD = 13); 40% were veterans of color. Women reporting military
sexual trauma had twice the odds of an eating disorder compared to women who did
not (odds ratio [OR]: 2.03; 95% CI [1.03-3.98]). Combat exposure was not
associated with eating disorders. Asian race (OR: 3.36; 95% CI [1.26-8.97]) and
age (OR: 1.03; 95% CI [1.01-1.06]) were associated with eating disorders.
CONCLUSIONS: The high rates of military sexual trauma and eating disorders
highlight a need for continued work. Results suggest that it may be useful to
focus on women reporting military sexual trauma when implementing eating disorder
screening and treatment programs. Given associations among trauma, eating
disorders, obesity, and mortality, such efforts could greatly improve veteran
health. (PsycINFO Database Record
PMID- 28493728
TI - Internal and community recourses' contribution to level of posttraumatic symptoms
The case of tourists after the earthquake in Nepal, 2015.
AB - OBJECTIVE: The current study focused on tourists who were caught in the middle of
Nepal's, 2015 earthquake, and survived. We examined the contribution of internal
(coping flexibility and emotional regulation) and community resources (sense of
belonging to the community) to tourist's level of post traumatic stress disorder
symptoms. METHOD: A cross-sectional sample survey was conducted to collect data
from 145 tourists between 2 week to 3 months after the earthquake. RESULTS: The
findings indicated first, that longer time which had elapsed since the earthquake
was correlated with lower level of posttraumatic symptoms. In addition, higher
versatility and cognitive reappraisal were associated with fewer symptoms of
posttrauma, whereas higher expressive suppression was associated with a higher
level of symptoms. Finally, the more the tourists believed they would get help
from other Israelis, the lower was their level of posttraumatic symptoms.
CONCLUSIONS: Tourists in a disaster area can be aided to develop a variety of
emotional, cognitive, and behavioral strategies that will assist them in coping
with the trauma. Furthermore, gathering tourists from the same country to conduct
interventions on the community level can be helpful. (PsycINFO Database Record
PMID- 28493730
TI - Behavioral health services in urban American Indian health organizations: A
descriptive portrait.
AB - The federal Indian Health Service (IHS) is the primary funding source for health
services designated for American Indians (AIs; Gone & Trimble, 2012). Urban
Indian health organizations (UIHOs), funded in part by IHS, are typically the
only sites in large metropolitan settings offering treatments tailored to AI
health needs. This is a first look at how mental health treatment is structured
at UIHOs. UIHO staff at 17 of 34 UIHOs responded to our request to participate
(50%), 14 employed behavioral health program directors who could complete the
survey on behalf of their programs, and 11 of these submitted complete data
regarding their current treatment practices and personal attitudes toward
empirically supported treatments. Reported treatment profiles differed less than
expected from available data on national outpatient clinics from the National
Mental Health Services Survey (Substance Abuse and Mental Health Services
Administration [SAMHSA], 2014), and program director attitudes toward empirically
supported treatments were similar to national norms reported by Aarons et al.
(2010). One way in which treatment differed was in the reported use of
traditional AI healing services. All program directors indicated that traditional
AI healing services were available within their behavioral health programs in
some form. These findings seem promising for the development of new empirically
supported treatments for AI clients, but also raise concerns, given what is known
about AI treatment preferences and mental health disparities. For example,
traditional healing services are often considered "alternative medicine," outside
the purview of evidence-based practice as typically construed by mental health
services researchers. This potential conflict is a subject for future research.
(PsycINFO Database Record
PMID- 28493729
TI - The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5): Development and initial
psychometric evaluation in military veterans.
AB - The Clinician-Administered PTSD Scale (CAPS) is an extensively validated and
widely used structured diagnostic interview for posttraumatic stress disorder
(PTSD). The CAPS was recently revised to correspond with PTSD criteria in the
fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM
5; American Psychiatric Association, 2013). This article describes the
development of the CAPS for DSM-5 (CAPS-5) and presents the results of an initial
psychometric evaluation of CAPS-5 scores in 2 samples of military veterans (Ns =
165 and 207). CAPS-5 diagnosis demonstrated strong interrater reliability (k =
.78 to 1.00, depending on the scoring rule) and test-retest reliability (k =
.83), as well as strong correspondence with a diagnosis based on the CAPS for DSM
IV (CAPS-IV; k = .84 when optimally calibrated). CAPS-5 total severity score
demonstrated high internal consistency (alpha = .88) and interrater reliability
(ICC = .91) and good test-retest reliability (ICC = .78). It also demonstrated
good convergent validity with total severity score on the CAPS-IV (r = .83) and
PTSD Checklist for DSM-5 (r = .66) and good discriminant validity with measures
of anxiety, depression, somatization, functional impairment, psychopathy, and
alcohol abuse (rs = .02 to .54). Overall, these results indicate that the CAPS-5
is a psychometrically sound measure of DSM-5 PTSD diagnosis and symptom severity.
Importantly, the CAPS-5 strongly corresponds with the CAPS-IV, which suggests
that backward compatibility with the CAPS-IV was maintained and that the CAPS-5
provides continuity in evidence-based assessment of PTSD in the transition from
DSM-IV to DSM-5 criteria. (PsycINFO Database Record
PMID- 28493731
TI - Pilot data of a brief veteran peer intervention and its relationship to mental
health treatment engagement.
AB - Underutilization of mental health care is a significant problem among veterans.
Offering peer support may improve mental health care engagement. This
observational pilot study was conducted using an institutional review board
approved data repository to preliminarily evaluate the association and potential
impact of a clinic-based veteran peer outreach strategy on treatment engagement
and dropout. Veteran peer outreach coordinators (VPOCs) provided systematic
contact (a) within 1 week after clinical evaluation and (b) 1 month after the
patient's first treatment session to patients entering treatment at a specialty
mental health clinic that provides military-informed mental health care to post
9/11 veterans and service members. Individuals were 102 consecutive Operation
Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn veteran psychotherapy
referrals seen at an outpatient clinic. At 6 months, participants who received
both contacts from VPOC had more psychotherapy sessions (M = 10.85, SD = 8.25)
compared with those who had received no contact (M = 5.47, SD = 6.41) from VPOCs,
t = 2.56, p < .05. The dropout rate was also significantly lower for those who
received both peer outreach contacts (17.39%) compared with those who received
only 1 VPOC contact (51.11%) or no VPOC contact (43.75%), chi2 = 7.27, p < .05.
Veteran peer outreach may be associated with better engagement in mental health
treatment and lower dropout. (PsycINFO Database Record (c) 2018 APA, all rights
reserved).
PMID- 28493732
TI - Psychological flexibility mitigates effects of PTSD symptoms and negative urgency
on aggressive behavior in trauma-exposed veterans.
AB - Recent literature suggests that posttraumatic stress disorder (PTSD) symptoms can
interact with personality factors to predict externalizing behaviors. Engagement
in externalizing behaviors such as substance abuse and aggressive behavior may,
in turn, increase risk for further trauma exposure and a more chronic course of
PTSD. In order to better understand how to intervene on this cycle, the current
study aimed to identify factors that could explain risk for externalizing
behaviors among trauma-exposed veterans. Moreover, we aimed to identify whether
psychological flexibility, a skill drawn from acceptance and commitment therapy
(ACT), may mitigate risk for engagement in externalizing behavior. Results
indicated that PTSD symptoms indirectly predicted externalizing behavior via
negative urgency, or the propensity to act rashly in the context of distress.
Moreover, psychological flexibility moderated this relationship such that
negative urgency was less strongly associated with aggressive behavior at high
levels of psychological flexibility. These results highlight moments of intense
distress as important targets for therapeutic intervention, and psychological
flexibility as a potentially important therapeutic skill for reducing
externalizing behavior among trauma-exposed individuals. (PsycINFO Database
Record
PMID- 28493733
TI - Dimensional conceptualizations of impulsivity.
AB - Impulsivity is a transdiagnostic dimension of crucial importance to understanding
psychopathology, as it is highly relevant to a wide array of maladaptive life
outcomes including substance use, criminality, and other risky behaviors. There
exist a variety of operationalizations of impulsivity across the literature
distinct nomological networks. In fact, research suggests that "impulsivity" is a
multifaceted construct comprised of at least 4 distinct traits that have unique
pathways to maladaptive behaviors. Those traits are positive and negative
urgency, sensation seeking, premeditation, and perseverance. Thus, it is crucial
that any diagnostic system, or model of maladaptive traits, capture the nuances
among these impulsigenic traits. The present study investigated the
conceptualization of impulsigenic traits within the Diagnostic and Statistical
Manual of Mental Disorders (DSM-5; American Psychiatric Association, 2013).
Alternative personality disorder model and an alternative trait model to
determine how well they captured these variants. This study obtained
questionnaire ratings and behavioral task data from 450 community-dwelling adults
oversampled for a history of involvement in the legal and/or mental health
systems. The results showed that although the DSM-5 trait model captures well a
broad conceptualization of impulsivity, some lower-order facets lack specificity.
(PsycINFO Database Record
PMID- 28493734
TI - Pubertal timing, racial identity, neighborhood, and school context among Black
adolescent females.
AB - OBJECTIVES: This study bridges the empirical research on pubertal timing effects,
racial identity, and school and neighborhood context to understand the pubertal
development and depression link among Black adolescent females. We examined
whether racial identity content dimensions moderated the relation between
pubertal timing and depressive symptoms among Black adolescent females and the
moderating capacity of school and neighborhood racial composition. METHOD: We
administered measures of pubertal development, racial identity, and depressive
symptoms to a sample of 217 Black adolescent females, aged 14 to 18. We assessed
racial centrality, private regard, and public regard and used archival data to
obtain the racial composition of participants' neighborhoods and schools.
RESULTS: The results indicated that high racial centrality levels were linked to
depressive symptoms for adolescent girls with late pubertal timing relative to
their early counterparts, which was stronger for girls attending not majority
Black schools. The results also indicated that low public regard levels were
linked to depressive symptoms among adolescent girls with early pubertal timing
relative to their late counterparts, which was stronger for girls attending not
majority Black schools. CONCLUSIONS: The current study provides evidence that
racial identity and school racial context moderate the effects of pubertal timing
differentially for early and late maturing Black girls. The results support the
notion that the psychological effects of pubertal timing on internalizing
symptoms are context dependent. (PsycINFO Database Record
PMID- 28493735
TI - Greater than the sum of its parts: Development of a measure of collectivism among
Asians.
AB - OBJECTIVES: Collectivism can contextualize subjective cultural experiences, yet
operationalization and measurement approaches for understanding this construct
among Asians and Asian Americans have been discrepant. Inconsistency has resulted
from diverse levels of analyses, unidimensional versus multidimensional
approaches to organizing related subconstructs, and different degrees of cultural
specificity of existing instruments. The Brief Collectivism Questionnaire (BCQ)
was developed to address these limitations in assessing general collectivism in
Asian cultures, while capturing its diverse attitudinal and behavioral
manifestations, using a bifactor framework. METHOD: Data were collected from 2
samples of Asian American and Asian international students (N1 = 267: Mage =
20.4, 48.7% women; N2 = 375: Mage = 19.0, 55.6% women). The structure underlying
collectivism was examined in exploratory (Study 1) and confirmatory (Study 2)
factor analyses. Correlational and hierarchical multiple regression analyses
tested the BCQ's validity, particularly the extent to which broadband
collectivism and content-specific subdomains overlapped with existing measures of
the construct (Study 3). RESULTS: A bifactor structure with 1 general factor of
collectivism and 3 specific factors (Prosocial Motivations, Maintaining Harmony,
and Concern for Face) demonstrated the best fit for the data and supported the
conceptual framework. The BCQ showed adequate internal consistency reliability,
convergent and discriminant validity, and concurrent and incremental validity
predicting depression and openness toward treatment seeking. CONCLUSIONS: The BCQ
appears to be a multidimensional, psychometrically sound measure that assesses
broadband and narrowband contents of collectivism among Asians. The bifactor
structure integrates diverse conceptualizations of individual-level collectivism,
and clarifies how this construct is related to adjustment outcomes. (PsycINFO
Database Record
PMID- 28493736
TI - Promoting mental health recovery and improving clinical assessment using video
technology.
AB - TOPIC: Although individuals with medical problems (e.g., diabetes, hypertension)
can monitor their symptoms using objective measures (e.g., blood glucose, blood
pressure), objective measures are not typically used by individuals with
psychotic disorders to monitor symptoms of mental illness. PURPOSE: To examine
the benefits and limitations of the use of video self-observation for treatment
of individuals with psychotic disorders. SOURCES USED: The authors reviewed
studies examining video self-observation among individuals with severe mental
illnesses. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Individuals with psychotic
disorders who viewed videos of themselves while symptomatic reported some benefit
to this approach, with 1 study showing sustained improvement in understanding of
mental illness. Still, some individuals reported negative feelings about the
process, and also attributed symptoms to stress or drug abuse rather than their
psychotic disorder. The authors found no studies examining the potential for
video self-observation as a strategy to improve clinical decision-making in the
context of mental health care. Implications of this approach for mental health
recovery and clinical practice are discussed. (PsycINFO Database Record
PMID- 28493737
TI - Autonomy support for conflictual and stigmatized identities: Effects on ownership
and psychological health.
AB - Important others' perceptions influence self-perceptions. This presents a
challenge for the critical developmental task of integrating all aspects of
identity, as identities that are devalued or stigmatized by society are harder to
own than valued ones. Across 3 studies, we tested the idea that conflictual or
stigmatized identities are harder to own, or integrate into the self, than are
nonconflictual ones, and we examine how receiving autonomy support for an
identity-support for authentic identity exploration and expression-can facilitate
ownership of that identity. Cross-sectional (n = 543), experience-sampling (n =
66), and experimental methods (n = 209) tested the dynamics of autonomy
supportive others on identity ownership. Data from these studies converge to show
that conflictual identities are indeed harder to own than nonconflictual ones,
but that autonomy support predicts greater ownership and psychological health,
especially for conflictual identities. In the final study, we replicate these
dynamics in 3 identities stigmatized by society: sexual minority, ethnic
minority, and gender minority identities. Findings reveal the importance of
integrating all aspects of identity-particularly those that are conflictual or
stigmatized-into one's self-concept. We consider implications for counseling and
clinical practice, as well as broadly for the psychological health of stigmatized
individuals. (PsycINFO Database Record
PMID- 28493738
TI - Helping others increases meaningful work: Evidence from three experiments.
AB - The aim of the current research was to examine whether manipulating task
significance increased the meaningfulness of work among students (Study 1), an
online sample of working adults (Study 2), and public university employees (Study
3). In Study 1, students completed a typing task for the benefit of themselves, a
charity, or someone they knew would directly benefit from their work. People who
worked to benefit someone else, rather than themselves, reported greater task
meaningfulness. In Study 2, a representative, online sample of employees
reflected on a time when they worked to benefit themselves or someone else at
work. Results revealed that people who reflected on working to benefit someone
else, rather than themselves, reported greater work meaningfulness. In Study 3,
public university employees participated in a community intervention by working
as they normally would, finding new ways to help people each day, or finding
several new ways to help others on a single day. People who helped others many
times in a single day experienced greater gains in work meaningfulness over time.
Across 3 experimental studies, we found that people who perceived their work as
helping others experienced more meaningfulness in their work. This highlights the
potential mechanisms practitioners, employers, and other parties can use to
increase the meaningfulness of work, which has implications for workers' well
being and productivity. (PsycINFO Database Record
PMID- 28493739
TI - Sample size determination for examining interaction effects in factorial designs
under variance heterogeneity.
AB - Moderation analysis is a vital aspect of research in education, management,
psychology, and related disciplines. Although several methodological artifacts
have been identified and examined, heterogeneity of variance remains one of the
unique and problematic factors known as detrimental to statistical power in the
detection of moderating effects. To alleviate the difficulty in assessing
moderation because of low statistical power, this article describes feasible
solutions to sample size calculations for tests of hypothesized interactions
between categorical variables under variance heterogeneity. Detailed numerical
illustrations and simulation studies are presented to demonstrate the feature and
usefulness of the suggested technique for 2- and 3-way factorial designs.
Moreover, SAS and R programs are provided to facilitate the implementation of the
proposed sample size procedure. (PsycINFO Database Record
PMID- 28493740
TI - Independent learning of spatial and nonspatial sequences.
AB - A small number of studies have examined whether learning the structures of two
uncorrelated sequences can proceed independently of one another. Limitations in
those studies have left their results open to alternative explanations. The
present study addressed the limitations. The visuospatial serial reaction time
task, initially introduced by Mayr (1996), was used to examine whether learning
the structure of a sequence of visuospatial target locations (spatial sequence)
and learning the structure of a sequence of target identities and responses
(nonspatial sequence) can proceed independently of one another. Employing a dual
sequence/single-sequence paradigm, learning a nonspatial sequence did not affect
learning a spatial sequence. This suggests that spatial sequence learning and
nonspatial sequence learning can proceed independently of one another. (PsycINFO
Database Record
PMID- 28493741
TI - How actions taken (or not) under alcohol influence inhibitory control and
perceived impairment.
AB - Consumption of alcohol can lead to the impairment of the ability to suppress
inappropriate responses. However, alcohol-induced disinhibition does not occur in
all contexts in the real world. Therefore, the purpose of this study was to
examine if actions taken (or not) under alcohol will impact observed inhibitory
control and how behavioral control requirements under alcohol alter perceived
levels of impairment. Participants (n = 40) of equal sex who were social drinkers
participated in a 3 session laboratory study that involved the administration of
placebo, 0.45g/kg, and 0.65g/kg doses of alcohol. Participants were randomly
assigned to a modified cued go/no-go reaction time (RT) task that included more
go trials (activational condition) or more no-go trials (inhibitory condition).
On all sessions after dose administration, participants completed their assigned
cued go/no-go computer task and gave subjective ratings of impairment. The
results indicated that participants in the activational condition under all doses
of alcohol, but particularly the highest dose of alcohol, displayed poorer
behavioral control (i.e., greater inhibitory failures) but self-reported lower
perceived impairment, when compared to participants in the inhibitory condition.
Therefore, this study provides laboratory evidence that alcohol consumption in an
active setting will lead to greater disinhibition and reduced perceptions of
impairment of behavior. The findings highlight the importance of the drinking
setting when examining the acute effects of alcohol and suggest potential avenues
for harm reduction for individuals who have difficulty controlling their alcohol
intake. (PsycINFO Database Record
PMID- 28493742
TI - Effects of alcohol, initial gambling outcomes, impulsivity, and gambling
cognitions on gambling behavior using a video poker task.
AB - Drinking and gambling frequently co-occur, and concurrent gambling and drinking
may lead to greater negative consequences than either behavior alone. Building on
prior research on the effects of alcohol, initial gambling outcomes, impulsivity,
and gambling cognitions on gambling behaviors using a chance-based (nonstrategic)
slot-machine task, the current study explored the impact of these factors on a
skill-based (strategic) video poker task. We anticipated larger average bets and
greater gambling persistence under alcohol relative to placebo, and expected
alcohol effects to be moderated by initial gambling outcomes, impulsivity, and
gambling cognitions. Participants (N = 162; 25.9% female) were randomly assigned
to alcohol (target BrAC = .08g%) or placebo and were given $10 to wager on a
simulated video poker task, which was programmed to produce 1 of 3 initial
outcomes (win, breakeven, or lose) before beginning a progressive loss schedule.
Despite evidence for validity of the video poker task and alcohol administration
paradigm, primary hypotheses were not supported. Individuals who received alcohol
placed smaller wagers than participants in the placebo condition, though this
effect was not statistically significant, and the direction of effects was
reversed in at-risk gamblers (n = 41). These findings contradict prior research
and suggest that alcohol effects on gambling behavior may differ by gambling type
(nonstrategic vs. strategic games). Interventions that suggest alcohol is
universally disinhibiting may be at odds with young adults' lived experience and
thus be less effective than those that recognize the greater complexity of
alcohol effects. (PsycINFO Database Record
PMID- 28493743
TI - Stimulus selectivity of drug purchase tasks: A preliminary study evaluating
alcohol and cigarette demand.
AB - The use of drug purchase tasks to measure drug demand in human behavioral
pharmacology and addiction research has proliferated in recent years. Few studies
have systematically evaluated the stimulus selectivity of drug purchase tasks to
demonstrate that demand metrics are specific to valuation of or demand for the
commodity under study. Stimulus selectivity is broadly defined for this purpose
as a condition under which a specific stimulus input or target (e.g., alcohol,
cigarettes) is the primary determinant of behavior (e.g., demand). The overall
goal of the present study was to evaluate the stimulus selectivity of drug
purchase tasks. Participants were sampled from the Amazon.com's crowdsourcing
platform Mechanical Turk. Participants completed either alcohol and soda purchase
tasks (Experiment 1; N = 139) or cigarette and chocolate purchase tasks
(Experiment 2; N = 46), and demand metrics were compared to self-reported use
behaviors. Demand metrics for alcohol and soda were closely associated with
commodity-similar (e.g., alcohol demand and weekly alcohol use) but not commodity
different (e.g., alcohol demand and weekly soda use) variables. A similar pattern
was observed for cigarette and chocolate demand, but selectivity was not as
consistent as for alcohol and soda. Collectively, we observed robust selectivity
for alcohol and soda purchase tasks and modest selectivity for cigarette and
chocolate purchase tasks. These preliminary outcomes suggest that demand metrics
adequately reflect the specific commodity under study and support the continued
use of purchase tasks in substance use research. (PsycINFO Database Record
PMID- 28493745
TI - "Treating adult survivors of childhood emotional abuse and neglect: A new
framework": Correction to Grossman et al. (2017).
AB - Reports an error in "Treating adult survivors of childhood emotional abuse and
neglect: A new framework" by Frances K. Grossman, Joseph Spinazzola, Marla Zucker
and Elizabeth Hopper (American Journal of Orthopsychiatry, 2017, Vol 87[1], 86
93). In the article, in the second sentence of the third paragraph of the "The
Empirical Base for CBP" section, "construction of a life narrative" should have
read "construction of a trauma narrative." The full corrected sentence follows:
"Therefore, the trauma treatment component traditionally focused upon
construction of a trauma narrative must be expanded to address the effects of
trauma on our clients' entire life narratives, including their development of a
sense of self and social identity." (The following abstract of the original
article appeared in record 2017-01147-002.) This article provides the outline of
a new framework for treating adult survivors of childhood emotional abuse and
neglect. Component-based psychotherapy (CBP) is an evidence-informed model that
bridges, synthesizes, and expands upon several existing schools, or theories, of
treatment for adult survivors of traumatic stress. These include approaches to
therapy that stem from more classic traditions in psychology, such as
psychoanalysis, to more modern approaches including those informed by feminist
thought. Moreover, CBP places particular emphasis on integration of key concepts
from evidence-based treatment models developed in the past few decades predicated
upon thinking and research on the effects of traumatic stress and processes of
recovery for survivors. (PsycINFO Database Record
PMID- 28493746
TI - Sexual objectification: The common thread connecting myriad forms of sexual
violence against women.
AB - In this article, the authors focus on the linkages between objectification and
current societal manifestations of sexual violence toward women to make the case
that everyday instances of objectification can provide the foundation for more
extreme forms of violence. First, they formally introduce the notion of
objectification and explain its origins and its consequences in those who
perpetrate and those who experience it. Next, they use objectification as a lens
through which to consider several related, but distinct, societal problems,
including: sexual assault of college women, harassment of women in work settings,
and sex trafficking of women in the United States and around the world. Finally,
they offer potential solutions, which, if implemented at individual,
organizational, and societal levels, could reduce violence against women in its
many forms. (PsycINFO Database Record
PMID- 28493744
TI - Does menthol cigarette use moderate the effect of nicotine metabolism on short
term smoking cessation?
AB - The nicotine metabolite ratio (NMR) has been shown to predict response to the
transdermal nicotine patch, such that faster nicotine metabolism is associated
with a lower abstinence rate. Menthol cigarette use, versus nonmenthol cigarette
use, slows nicotine metabolism and therefore may attenuate the effect of NMR on
smoking abstinence. In this study, we evaluated whether cigarette type (menthol
vs. nonmenthol) modified the association between NMR and short-term abstinence.
This was a secondary analysis examining treatment in the first 8 weeks of 21
mg/day nicotine patch therapy in a completed clinical trial (n = 474). Menthol
cigarette use was based on self-report. NMR was defined dichotomously (0 = fast,
1 = slow) to distinguish between fast (>=0.47) versus slow NMR. Using logistic
regression analysis, we tested whether cigarette type moderated the association
between NMR and bioverified 7-day point prevalence abstinence at Week 8.
Covariates include nicotine dependence, age, race, and gender. Three hundred two
participants reported smoking menthol cigarettes, of which 234 (77%) were
classified as slow NMR. Among the 172 nonmenthol smokers, 136 were classified as
slow NMR (79%). Contrary to our expectations, the NMR *Cigarette Type interaction
effect on abstinence was not significant (odds ratio [OR] = 0.91, p = .86).
Excluding the interaction variable, fast NMR was associated with decreased
likelihood of abstinence (OR = 0.55, p = .03), but menthol cigarette use was not
(OR = 1.15, p = .56). Further exploration of risk factors among menthol cigarette
smokers, especially among racially diverse and light smokers, could clarify the
association between menthol cigarette use and poorer smoking outcomes. (PsycINFO
Database Record
PMID- 28493747
TI - Leader social accounts of subordinates' unethical behavior: Examining observer
reactions to leader social accounts with moral disengagement language.
AB - When providing social accounts (Sitkin & Bies, 1993) for the unethical conduct of
subordinates, leaders may use language consistent with cognitive strategies
described by Bandura (1991, 1999) in his work on moral disengagement. That is,
leader's social accounts may reframe or reconstrue subordinates' unethical
conduct such that it appears less reprehensible. We predict observers will
respond negatively to leaders when they use moral disengagement language within
social accounts and, specifically, observers will ostracize these leaders. In
addition, we predict that observer moral disengagement propensity moderates this
effect, such that the relationship between leaders' use of moral disengagement
language within a social account and ostracism is stronger when observer moral
disengagement propensity is lower versus higher. Finally, we predict that the
reason why observers ostracize the leader is because observers perceive the
leader's social account with moral disengagement language as unethical. Thus,
perceived leader social account ethicality is predicted to mediate the
interaction effect of leader's use of moral disengagement language within social
accounts and observer moral disengagement propensity on ostracism. Results from
an experiment and field study support our predictions. Implications for theory
and practice are discussed. (PsycINFO Database Record
PMID- 28493748
TI - The face of fear and anger: Facial width-to-height ratio biases recognition of
angry and fearful expressions.
AB - The ability to rapidly and accurately decode facial expressions is adaptive for
human sociality. Although judgments of emotion are primarily determined by
musculature, static face structure can also impact emotion judgments. The current
work investigates how facial width-to-height ratio (fWHR), a stable feature of
all faces, influences perceivers' judgments of expressive displays of anger and
fear (Studies 1a, 1b, & 2), and anger and happiness (Study 3). Across 4 studies,
we provide evidence consistent with the hypothesis that perceivers more readily
see anger on faces with high fWHR compared with those with low fWHR, which
instead facilitates the recognition of fear and happiness. This bias emerges when
participants are led to believe that targets displaying otherwise neutral faces
are attempting to mask an emotion (Studies 1a & 1b), and is evident when faces
display an emotion (Studies 2 & 3). Together, these studies suggest that target
facial width-to-height ratio biases ascriptions of emotion with consequences for
emotion recognition speed and accuracy. (PsycINFO Database Record
PMID- 28493749
TI - Maternal emotion dysregulation and the functional organization of preschoolers'
emotional expressions and regulatory behaviors.
AB - Although psychopathology in mothers is known to be a significant risk factor for
child outcomes, less is known about how emotion dysregulation, a transdiagnostic
feature that cuts across many diagnoses, shapes emotion-related parenting
practices and the development of emotion regulation in offspring. Building upon
previous research that examined the functional relations between emotions and
regulatory actions in children, we sought to examine the association of maternal
emotion dysregulation and emotion socialization with these functional links in an
at-risk community sample of mother-preschooler (children ages 36-60 months) dyads
that oversampled for mothers with elevated symptoms of borderline personality
disorder (n = 68). We found that maternal emotion dysregulation was associated
with children displaying more sadness and engaging in less problem solving during
the Locked Box Task, which is designed to elicit anger. Maternal emotion
dysregulation was also associated with children being more distracted and talking
less in the context of sadness. Maternal nonsupportive emotion socialization
responses were associated with children engaging in more defiant behaviors
throughout the task and using less problem solving in the context of happiness,
whereas maternal supportive emotion socialization responses were associated with
more play throughout the task and less talking in the context of sadness, above
and beyond the effect of maternal emotion dysregulation. These findings indicate
that maternal emotion dysregulation and nonsupportive emotion socialization
practices are both meaningfully associated with the development of aberrant
patterns of emotional and behavioral responding during the preschool years.
(PsycINFO Database Record
PMID- 28493750
TI - The ideal road not taken: The self-discrepancies involved in people's most
enduring regrets.
AB - Research on the structural features of people's most enduring regrets has focused
on whether they result from having acted or having failed to act. Here we focus
on a different structural feature, their connection to a person's self-concept.
In 6 studies, we predict and find that people's most enduring regrets stem more
often from discrepancies between their actual and ideal selves than their actual
and ought selves. We also provide evidence that this asymmetry is at least partly
due to differences in how people cope with regret. People are quicker to take
steps to cope with failures to live up to their duties and responsibilities
(ought-related regrets) than their failures to live up to their goals and
aspirations (ideal-related regrets). As a consequence, ideal-related regrets are
more likely to remain unresolved, leaving people more likely to regret not being
all they could have been more than all they should have been. (PsycINFO Database
Record
PMID- 28493751
TI - Identity change among smokers and ex-smokers: Findings from the ITC Netherlands
Survey.
AB - Successful smoking cessation appears to be facilitated by identity change, that
is, when quitting or nonsmoking becomes part of smokers' and ex-smokers' self
concepts. The current longitudinal study is the first to examine how identity
changes over time among smokers and ex-smokers and whether this can be predicted
by socioeconomic status (SES) and psychosocial factors (i.e., attitude, perceived
health damage, social norms, stigma, acceptance, self-evaluative emotions, health
worries, expected social support). We examined identification with smoking (i.e.,
smoker self-identity) and quitting (i.e., quitter self-identity) among a large
sample of smokers (n = 742) and ex-smokers (n = 201) in a cohort study with
yearly measurements between 2009 and 2014. Latent growth curve modeling was used
as an advanced statistical technique. As hypothesized, smokers perceived
themselves more as smokers and less as quitters than do ex-smokers, and
identification with smoking increased over time among smokers and decreased among
ex-smokers. Furthermore, psychosocial factors predicted baseline identity and
identity development. Socioeconomic status (SES) was particularly important.
Specifically, lower SES smokers and lower SES ex-smokers identified more strongly
with smoking, and smoker and quitter identities were more resistant to change
among lower SES groups. Moreover, stronger proquitting social norms were
associated with increasing quitter identities over time among smokers and ex
smokers and with decreasing smoker identities among ex-smokers. Predictors of
identity differed between smokers and ex-smokers. Results suggest that SES and
proquitting social norms should be taken into account when developing ways to
facilitate identity change and, thereby, successful smoking cessation. (PsycINFO
Database Record
PMID- 28493752
TI - Problem gambling symptomatology and alcohol misuse among adolescents: A parallel
process latent growth curve model.
AB - The objective of the current study was to examine the possible temporal
associations between alcohol misuse and problem gambling symptomatology from
adolescence through to young adulthood. Parallel-process latent growth curve
modeling was used to examine the trajectories of alcohol misuse and symptoms of
problem gambling over time. Data were from a sample of adolescents recruited for
the Leisure, Lifestyle, and Lifecycle Project in Alberta, Canada (n = 436), which
included 4 assessments over 5 years. There was an average decline in problem
gambling symptoms followed by an accelerating upward trend as the sample reached
the legal age to gamble. There was significant variation in the rate of change in
problem gambling symptoms over time; not all respondents followed the same
trajectory. There was an average increase in alcohol misuse over time, with
significant variability in baseline levels of use and the rate of change over
time. The unconditional parallel process model indicated that higher baseline
levels of alcohol misuse were associated with higher baseline levels of problem
gambling symptoms. In addition, higher baseline levels of alcohol misuse were
associated with steeper declines in problem gambling symptoms over time. However,
these between-process correlations did not retain significance when covariates
were added to the model, indicating that one behavior was not a risk factor for
the other. The lack of mutual influence in the problem gambling symptomatology
and alcohol misuse processes suggest that there are common risk factors
underlying these two behaviors, supporting the notion of a syndrome model of
addiction. (PsycINFO Database Record
PMID- 28493753
TI - Visual attention to alcohol cues and responsible drinking statements within
alcohol advertisements and public health campaigns: Relationships with drinking
intentions and alcohol consumption in the laboratory.
AB - Both alcohol advertising and public health campaigns increase alcohol consumption
in the short term, and this may be attributable to attentional capture by alcohol
related cues in both types of media. The present studies investigated the
association between (a) visual attention to alcohol cues and responsible drinking
statements in alcohol advertising and public health campaigns, and (b) next-week
drinking intentions (Study 1) and drinking behavior in the lab (Study 2). In
Study 1, 90 male participants viewed 1 of 3 TV alcohol adverts (conventional
advert; advert that emphasized responsible drinking; or public health campaign;
between-subjects manipulation) while their visual attention to alcohol cues and
responsible drinking statements was recorded, before reporting their drinking
intentions. Study 2 used a within-subjects design in which 62 participants (27%
male) viewed alcohol and soda advertisements while their attention to
alcohol/soda cues and responsible drinking statements was recorded, before
completing a bogus taste test with different alcoholic and nonalcoholic drinks.
In both studies, alcohol cues attracted more attention than responsible drinking
statements, except when viewing a public health TV campaign. Attention to
responsible drinking statements was not associated with intentions to drink
alcohol over the next week (Study 1) or alcohol consumption in the lab (Study 2).
However, attention to alcohol portrayal cues within alcohol advertisements was
associated with ad lib alcohol consumption in Study 2, although attention to
other types of alcohol cues (brand logos, glassware, and packaging) was not
associated. Future studies should investigate how responsible drinking statements
might be improved to attract more attention. (PsycINFO Database Record
PMID- 28493754
TI - Discrepancy in caregiving expectations predicts problematic alcohol use among
caregivers of trauma injury patients six months after ICU admission.
AB - This prospective study examined the influence of caregiving variables on the
development of problematic alcohol use among family members of patients admitted
to an urban Level I trauma center. Data were collected from 124 caregivers 48 hrs
after initial hospitalization of their family member. The final sample included
81 participants (24.6% male; Mage = 47.8) who completed their follow-up
assessment at 6 months. Hierarchical linear and logistic regression analyses
assessed increases in consumption and odds of a positive screen for problematic
alcohol use in association with caregiver burden, actual time spent in the
caregiving role, and caregiving differential (i.e., anticipated time spent
caregiving at baseline in relation to actual time caregiving at 6 months). At 6
months, 24.7% of caregivers screened positive for problematic alcohol use.
Results uniquely highlighted caregiving differential as a significant predictor
of both increases in general alcohol consumption (DeltaR2 = .06, p < .01) and
odds of screening positive for problematic alcohol use at 6 months (Odds Ratio =
1.05, 95% CI [1.02-1.09]). More specifically, our adjusted model found that
providing 10% more time caregiving, relative to expectations at baseline, was
associated with an increase in the probability of problematic alcohol use by 22%
(95% CI: 8-37%) at 6 months. These results suggest that a discrepancy in
expectations regarding anticipated time caregiving and actual time caregiving,
rather than solely the amount of caregiving or perceived caregiver burden, may be
an important predictor of caregiver alcohol use 6 months after a family member's
ICU hospitalization. (PsycINFO Database Record
PMID- 28493755
TI - Affect contagion between mothers and infants: Examining valence and touch.
AB - Mothers and their babies represent one of the closest dyadic units and thus
provide a powerful paradigm to examine how affective states are shared, and
result in, synchronized physiologic responses between two people. We recruited
mothers and their 12- to 14-month-old infants (Ndyads = 98) to complete a lab
study in which mothers were initially separated from their infants and assigned
to either a low-arousal positive/relaxation condition, intended to elicit
parasympathetic nervous system (PNS) reactivity, or a high-arousal
negative/stress task, intended to elicit sympathetic nervous system (SNS)
reactivity. Upon reunion, infants were placed either on their mothers' laps
(touch condition) or in a high chair next to the mother (no-touch condition). We
then examined if the babies SNS and/or PNS responses changed from their baseline
levels and how the dyads' physiological responses-both PNS and SNS responses
synchronized over time as a function of mothers' affect manipulation and touch
condition. Three noteworthy findings were observed. First, infants of mothers
assigned to the relaxation task showed greater PNS increases and PNS covariation.
Second, infants of mothers assigned to the stress task showed stronger SNS
covariation with their mothers over time. Finally, infants who sat on their
mothers' laps (i.e., touch condition) showed stronger SNS covariation than those
in the no-touch condition. Taken together, these results suggest that mothers'
affective states-low-arousal positive states as well as high-arousal negative
states-can be "caught" by their infants, and that touch can play a critical role
in stress contagion. (PsycINFO Database Record
PMID- 28493756
TI - Functional consequences of compositional spatial representations elicited during
conceptual control of visual spatial attention.
AB - Reference frames are ubiquitous in spatial cognition, and they have been
especially important in the visual attention literature. Researchers typically
invoke these constructs to explain how the same physical location can be defined
in different ways depending on changes in the reference point. However, when
researchers invoke reference frames for this purpose, they also tend to invoke a
construct-the Cartesian coordinate system-that has a specific compositional
structure. This conclusion may not be warranted though because reference frames
can be used to define a location without being compositional in nature. The
present study used an attention cuing paradigm to examine the potential
consequences of encoding spatial locations within compositional (coordinate)
spatial representations. Experiment 1 used 75% valid, compositional cues that
conveyed separate information about the likely direction and distance of the
target. The main results were consistent with the notion that a Cartesian
coordinate reference system was used to interpret these cues which in turn
elicited a compositional gradient that reflected the combined activation arising
from the separate spatial dimensions. Experiment 2 ruled out an alternative
account and Experiment's 3 and 4 examined the dynamic nature of these gradients
over time. These findings were interpreted within a theory of conceptual control
that distinguished between conceptual and perceptual representations of space.
Conceptual representations are compositional and can be used to guide attention
from one object to another. But conceptual representations depend on
noncompositional, perceptual representations to bind the activations arising from
their separate spatial dimensions, much like nonspatial feature dimensions do.
(PsycINFO Database Record
PMID- 28493757
TI - Argumentation and the diffusion of counter-intuitive beliefs.
AB - Research in cultural evolution has focused on the spread of intuitive or
minimally counterintuitive beliefs. However, some very counterintuitive beliefs
can also spread successfully, at least in some communities-scientific theories
being the most prominent example. We suggest that argumentation could be an
important factor in the spread of some very counterintuitive beliefs. A first
experiment demonstrates that argumentation enables the spread of the
counterintuitive answer to a reasoning problem in large discussion groups,
whereas this spread is limited or absent when participants can show their answers
to each other but cannot discuss. A series of experiments using the technique of
repeated transmission show that, in the case of the counterintuitive belief
studied: (a) arguments can help spread this belief without loss; (b) conformist
bias does not help spread this belief; and (c) authority or prestige bias play a
minimal role in helping spread this belief. Thus, argumentation seems to be
necessary and sufficient for the spread of some counterintuitive beliefs.
(PsycINFO Database Record
PMID- 28493758
TI - Lying because we care: Compassion increases prosocial lying.
AB - Prosocial lies, or lies intended to benefit others, are ubiquitous behaviors that
have important social and economic consequences. Though emotions play a central
role in many forms of prosocial behavior, no work has investigated how emotions
influence behavior when one has the opportunity to tell a prosocial lie-a
situation that presents a conflict between two prosocial ethics: lying to prevent
harm to another, and honesty, which might also provide benefits to the target of
the lie. Here, we examine whether the emotion of compassion influences prosocial
lying, and find that compassion causally increases and positively predicts
prosocial lying. In Studies 1 and 2, participants evaluated a poorly written
essay and provided feedback to the essay writer. Experimentally induced
compassion felt toward the essay writer (Study 1) and individual differences in
trait compassion (Study 2) were positively associated with inflated feedback to
the essay writer. In both of these studies, the relationship between compassion
and prosocial lying was partially mediated by an enhanced importance placed on
preventing emotional harm. In Study 3, we found moderation such that
experimentally induced compassion increased lies that resulted in financial gains
for a charity, but not lies that produced financial gains for the self. This
research illuminates the emotional underpinnings of the common yet morally
complex behavior of prosocial lying, and builds on work highlighting the
potentially harmful effects of compassion-an emotion typically seen as socially
beneficial. (PsycINFO Database Record
PMID- 28493759
TI - "Characterizing autism-relevant social behavior in poodles (Canis familiaris) via
owner report": Correction to Zamzow et al. (2017).
AB - Reports an error in "Characterizing Autism-Relevant Social Behavior in Poodles
via Owner Report" by Rachel M. Zamzow, Lisa Lit, Shelley Hamilton and David Q.
Beversdorf (Journal of Comparative Psychology, Advanced Online Publication, Mar
13, 2017, np). In the article, the scientific name for the species was missing in
the title. All versions of this article have been corrected. (The following
abstract of the original article appeared in record 2017-11247-001.) Autism
spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by
deficits in social communication and the presence of restricted, repetitive
behaviors. It can be difficult to model the complex behavioral features of this
disorder with rodent models, which have limited similarity to human behaviors.
The domestic dog may be a promising model of complex human behavior, including
core features of ASD. The present study examines ASD-relevant social behavior in
Miniature and Standard Poodles using an owner-report questionnaire with questions
adapted from the Autism Diagnostic Observation Schedule (Lord, Rutter, DiLavore,
& Risi, 2000). A previous study identified 3 behavioral constructs examined by
this questionnaire: initiation of reciprocal social behaviors, response to social
interaction, and communication. In the present study, confirmatory and
experimental factor analyses used to assess how collected data fit with the
previous model revealed moderate model fit and a similar factorial structure.
Between-breed comparisons across these factors and at the individual question
level revealed differences between Miniature and Standard Poodles in showing
behaviors. Cluster analyses used to group dogs within each breed according to
social behavior identified smaller subgroups of dogs with less social behavior
across all 3 factors compared with the average within each breed. Within- and
between-breed differences in social behavior warrant investigation of genetic
variation underlying this complex trait as it relates to ASD-relevant behavior.
(PsycINFO Database Record
PMID- 28493760
TI - Exploration of the ASCO and ESMO Value Frameworks for Antineoplastic Drugs.
AB - PURPOSE: In 2015, both ASCO and the European Society for Medical Oncology (ESMO)
proposed frameworks to quantify the benefit of antineoplastic drugs in the face
of rising costs. We applied these frameworks to drugs approved by the US Food and
Drug Administration over the past 12 years and examined relationships between
costs and benefits. METHODS: We searched FDA.gov for drugs that received initial
approval for solid tumors from 2004 to 2015 and calculated the ASCO Net Health
Benefit version 2016 (NHB16) and 2015 (NHB15) and the ESMO Magnitude of Clinical
Benefit Scale scores for each drug. We calculated descriptive statistics and
explored correlations and associations among benefit scores, cost, and
independent variables. RESULTS: We identified 55 drug approvals supported by
phase II (18.2%) and III (81.8%) trials, with primary outcomes of overall
survival (36.4%), progression-free survival (43.6%), or response rate (20.0%). No
significant association was found between NHB16 and year of approval ( P = .81),
organ system ( P = .20), or trial comparator arm ( P = .17), but trials with
progression-free survival outcomes were associated with higher scores ( P =
.007). Both NHB15 and Magnitude of Clinical Benefit Scale scores were
approximately normally distributed, but only a moderate correlation existed
between them ( r = 0.40, P = .006). No correlation between benefit score and cost
(NHB16, r = 0.19; ESMO, r = -0.07) was found. Before 2010, two (15.3%) of 13
approved drugs exceeded $500/NHB point * month compared with 10 (25.0%) of 40
drugs subsequently approved. CONCLUSION: Our analysis of the ASCO and ESMO value
frameworks illuminates the heterogeneous benefit of new medications and
highlights challenges in constructing a unified concept of drug value. Drug
benefit does not correlate with cost, and the number of high cost/benefit
outliers has increased.
PMID- 28493761
TI - Pursuing Interventions for an Incurable Cancer: Adding to Hope or Delusion?
PMID- 28493762
TI - Why Burnout Is So Hard to Fix.
PMID- 28493763
TI - Fluorescent PCR detection of mecA in drug resistant MRSA: a methodological study.
PMID- 28493764
TI - Nursing: it's just what we do.
PMID- 28493765
TI - Long-term urethral catheterisation: guidelines for community nurses.
AB - An estimated 3% of people living in the community and 12% of those living in
residential care use long-term urethral catheterisation for the management of
urine drainage. This article provides an overview of safe practice for
catheterisation in the community setting, highlighting the need for competent and
safe patient assessments. It also aims to provide a rationale for product
choices.
PMID- 28493766
TI - UK Chief Nursing Officers: shaping the future of the profession.
AB - In celebration of International Nurses Day, Jane Cummings, Charlotte McArdle,
Fiona McQueen and Jean White, Chief Nursing Officers (CNOs) for England, Northern
Ireland, Scotland and Wales.
PMID- 28493767
TI - Nursing a critically ill tetanus patient in an intensive care unit in Zambia.
AB - The global incidence of tetanus has been gradually reducing. Improvements in
vaccination and health education programmes and the World Health Organization
campaign to eradicate maternal and neonatal tetanus have all resulted in fewer
presentations globally. Unfortunately, tetanus mortality remains a significant
problem for many developing countries, owing to inadequate vaccination programmes
or to conflict or humanitarian disasters during which vaccination programmes are
stopped or there is sporadic cover. This case study explores the care of a
tetanus patient in an intensive care unit in Zambia, a lower-middle-income
country in sub-Saharan Africa.
PMID- 28493769
TI - We have made history, but what about our future?
PMID- 28493768
TI - Protecting whistleblowers against discrimination in the NHS.
AB - Emeritus Professor Alan Glasper, from the University of Southampton, discusses
new Department of Health proposals to prohibit discrimination against former
whistleblowers when they apply for another job in the NHS.
PMID- 28493770
TI - Lower urinary tract infections in women.
AB - In her lifetime, a woman is highly likely to develop at least one lower urinary
tract infection. Early detection and treatment are key. Being aware of
predisposing factors for infection and understanding appropriate diagnosis and
treatment regimens will help nurses in both primary and acute care manage these
patients correctly. This will not only benefit patients but will also help
prevent incorrect antimicrobial management and avoid unplanned admissions. This
aim of this article is to provide nurses with the information they need to best
advise both colleagues and patients on how to manage lower urinary tract
infections in women.
PMID- 28493771
TI - Introducing a device to assist in the application of anti-embolism stockings.
AB - Using a device to help with the application and removal of anti-embolism
stockings, often called thromboembolic deterrent stockings (TEDS), can
potentially facilitate greater adherence to the use of stockings, and potentially
reduce the risk of deep-vein thrombosis (DVT). This article describes a quality
improvement project which used the Plan, Do, Study, Act (PDSA) cycle to
facilitate the introduction of a device to aid in the application of
thromboembolic deterrent stockings in an orthopaedic ward. The project findings
showed that Neo-slip(r), a product designed to facilitate the use of compression
stockings, can be effectively introduced into an orthopaedic ward, with positive
feedback from both staff and patients.
PMID- 28493772
TI - Strength through adversity: developing resilience though international working.
PMID- 28493773
TI - How amendments to the Mental Health Act 1983 will change police powers.
AB - Richard Griffith, Senior Lecturer in Health Law at Swansea University, considers
the impact on nursing practice of amendments to police powers under the Mental
Health Act 1983 introduced by the Policing and Crime Act 2017.
PMID- 28493774
TI - Urinary catheter-related visits to the emergency department and implications for
community services.
AB - : Thousands of patients live with urinary catheters and the potential
complications deriving from long-term use. Disjointed community services may
result in patients attending the emergency department (ED) to manage catheter
complications. AIM: to conduct a service review of catheterised patients
attending the ED of a large London hospital; to describe incidence, reasons for
attendance and cost to inform future planning for out-of-hospital care. METHOD: a
catheter collaborative, consisting of multidisciplinary health professionals and
patients, formulated survey questions. Patients were identified from the
electronic patient record by searching for the code 'urological complaint'. One
month of clinical records were retrospectively reviewed and analysed using
descriptive statistics. RESULTS: 287 patients attended the department with
urological complaints: 41 (14%) had urinary catheter problems, of these 24 (59%)
patients were discharged and 17 (41%) were admitted for further treatment. Stays
in ED varied from 1 hour 13 minutes to 17 hours (mean = 4.8 hours). A total of 9
patients (38%) were sent home during antisocial hours (9 pm to 7 am), 4 patients
were discharged between midnight and 2 am. Patients admitted had mean stays of
4.11 days. Most admissions were short term for intravenous (IV) treatments; 3
patients were hospitalised for 20 days. A total of 14 patients (34%) were
diagnosed with catheter-related infections: 11 (79%) had bladder infections and 3
(21%) had septicaemia. All 14 patients (100%) had urine-culture-confirmed
infections, mainly from coliform, proteus and pseudomonas species. A total of 20
patients (49%) received antibiotic treatment. The majority of patients received
an initial IV dose followed, where required, by oral treatment on discharge.
CONCLUSIONS: many catheterised patients had complex needs with high rates of
urinary infections and admissions for urosepsis. High attendance related less to
old age but more to complexity of history, such as neurological conditions and
disability. Only a proportion of these patients could be safely treated by
district nurse teams. A significant proportion would require more responsive
community services with several spells of short-term input (e.g. daily or more
than once-daily visits) and access to diagnostics, microbiology, pharmaceutical
input and IV treatments.
PMID- 28493776
TI - Nurses: A Voice to Lead.
AB - The International Council of Nurses celebrates nurses' contributions to the
Sustainable Development Goals.
PMID- 28493775
TI - The key to personalised medicine.
AB - Sam Foster, Chief Nurse at Heart of England NHS Foundation Trust, has been
brushing up on her understanding of genomics, and the opportunities it presents
to the NHS.
PMID- 28493777
TI - Let's face the future together.
PMID- 28493778
TI - Urinary continence care for older people in the acute setting.
PMID- 28493779
TI - Understanding the global causes and costs of patient harm.
AB - John Tingle, Reader in Health Law at Nottingham Trent University, discusses the
Organisation for Economic Co-operation and Development's report on the economics
of patient safety.
PMID- 28493780
TI - Nursing students' experiences of mentorship in their final placement.
AB - AIM: The aim of this study was to explore final-year students' experiences of the
mentorship role in their final placement and, in particular, to establish their
expectations of the mentorship role, as well as their support and supervision
needs. METHOD: Seven final-placement students were recruited from one Scottish
university, using purposive sampling. Heideggerian phenomenology was chosen as
the underpinning philosophical approach because of its emphasis on the 'lived
experience'. Data were generated using unstructured interviews and analysed using
a modified version of Colaizzi's procedural steps. RESULTS: Five themes emerged
from the data: 'being more independent', 'support', 'belongingness', 'feedback'
and 'anticipatory anxiety'. DISCUSSION: Participants who had a positive
experience of mentorship were exposed to a 'good' learning environment. As a
result, they felt supported, received adequate opportunities to practise
management skills, had a sense of 'belonging' within the nursing team and had
regular feedback. Those who had a negative experience complained of not getting
the opportunity to develop essential management skills and being dismissed for
trying to be proactive. In addition, feedback was reported to be lacking. This
experience resulted in reduced confidence levels, which left them feeling
unprepared for the transition to registered nurse. CONCLUSION: The clinical
learning environment itself and support from the mentor are key factors that
influence student preparation for registration. Without this level of support,
students may be left feeling unprepared to deal with the transition.
PMID- 28493781
TI - Juggling two roles: flexibility is the key.
PMID- 28493782
TI - Is CPR always appropriate? A personal perspective from working in East Africa.
PMID- 28493783
TI - Your nursing degree: an international ticket to see the world.
PMID- 28493784
TI - Religion, spirituality and belief: is this the business of nurses?
AB - Janet Scammell, Associate Professor (Nursing), Bournemouth University, considers
whether nurses receive sufficient education on religion and spirituality in pre
registration education.
PMID- 28493785
TI - Working in partnership: Somaliland.
PMID- 28493786
TI - Mitigating perceptual error with 'look, listen, feel'.
AB - Duncan Hamilton, Second Year Student, Adult Nursing, University of Surrey, shares
how he came to reconsider the arguments for a hands-on approach to taking a
pulse.
PMID- 28493787
TI - Impact of Therapy on Recovery during Rehabilitation in Patients with Traumatic
Spinal Cord Injury.
AB - Evidence-based planning of rehabilitation interventions is important to improving
cost efficiency while maintaining patient and system outcomes. This article aims
to explore the relationship between rehabilitation therapy, functional outcome,
bed utilization, and care costs after traumatic spinal cord injury (tSCI). A
retrospective review of 262 persons with tSCI admitted to an inpatient
rehabilitation facility from 2005-2012 was conducted. Treatment variables and
outcome measures included rehabilitation length of stay (LOS), days to
rehabilitation (onset), hours and intensity of therapy, and Functional
Independence Measure (FIM). Polynomial regression models and generalized additive
models were applied to explore the relationship between therapy hours and motor
FIM change. Simulation modeling was used to assess the impact of hypothetically
increasing therapy intensity. Patients were grouped by injury as: C1-4 American
Spinal Injury Association (ASIA) Impairment Scale (AIS) A,B,C; C5-8 AIS A,B,C; T1
S5 AIS A,B,C; and AIS D. The sample was 85% male, mean age 45.9, median LOS 102
days, and mean therapy intensity 5.7 h/week. Motor FIM change was positively
associated with total hours of therapy (beta = 0.40, p < 0.0001) up to a certain
time point, adjusted for age, gender, injury, complications, and rehabilitation
onset. Hypothetically increasing therapy intensity by 50% and 100% resulted in
average motor FIM efficiency gain ranging between 0.04-0.07 and 0.1-0.17,
respectively, across injury groups. The hypothetical changes resulted in
reductions in the average LOS and bed utilization rate, translating to cost
savings of $20,000 and $50,000 (2011 CAD) for the +50% and +100% scenarios,
respectively. The results highlight the importance of monitoring functional
change throughout rehabilitation after tSCI and the need for customized
therapeutic strategies.
PMID- 28493788
TI - Development of In Vitro Embryo Production System Using Collagen Matrix Gel
Attached with Vascular Endothelial Growth Factor Derived from Interleukin-1 Beta
Treated Porcine Endometrial Tissue.
AB - The aim of this study was to establish an embryo culture system using collagen
gel attached with vascular endothelial growth factor (VEGF) derived from
interleukin-1 beta (IL-1beta)-treated endometrial tissues from pigs. Endometria
were separated from the porcine uterus at the follicular phase of the estrous
cycle and were cultured with IL-1beta. The collagen gels coincubated with IL
1beta-treated endometria (C, without endometrial tissue; CE, with endometrial
tissue; and CEI, IL-1beta-treated endometrial tissue) were used for embryo
culture. We found that, compared with the comparable figures in the control
group, prostaglandin synthase-2 (PTGS-2) mRNA was increased in IL-1beta-treated
endometrial tissue (p < 0.05). The VEGF protein was not observed in collagen gel
coincubated without endometrial tissue (C); however, it was detected in collagen
gels coincubated with endometrial tissue (CE and CEI). The embryo cleavage rates
and blastocyst formation did not differ among the treatment groups. The
proportion of blastocysts did not differ among the groups. However, the number of
blastocyst cells was significantly (p < 0.05) higher in the CEI group than in the
other groups. These results clarify the effects of the intrauterine environment
on preimplantation embryos and may be useful in research on the effects of
extracellular matrix- and cytokine-treated endometrial tissue on embryo
development.
PMID- 28493789
TI - Idiopathic Pulmonary Fibrosis: Data-driven Textural Analysis of Extent of
Fibrosis at Baseline and 15-Month Follow-up.
AB - Purpose To evaluate associations between pulmonary function and both quantitative
analysis and visual assessment of thin-section computed tomography (CT) images at
baseline and at 15-month follow-up in subjects with idiopathic pulmonary fibrosis
(IPF). Materials and Methods This retrospective analysis of preexisting
anonymized data, collected prospectively between 2007 and 2013 in a HIPAA
compliant study, was exempt from additional institutional review board approval.
The extent of lung fibrosis at baseline inspiratory chest CT in 280 subjects
enrolled in the IPF Network was evaluated. Visual analysis was performed by using
a semiquantitative scoring system. Computer-based quantitative analysis included
CT histogram-based measurements and a data-driven textural analysis (DTA). Follow
up CT images in 72 of these subjects were also analyzed. Univariate comparisons
were performed by using Spearman rank correlation. Multivariate and longitudinal
analyses were performed by using a linear mixed model approach, in which models
were compared by using asymptotic chi2 tests. Results At baseline, all CT-derived
measures showed moderate significant correlation (P < .001) with pulmonary
function. At follow-up CT, changes in DTA scores showed significant correlation
with changes in both forced vital capacity percentage predicted (rho = -0.41, P <
.001) and diffusing capacity for carbon monoxide percentage predicted (rho =
0.40, P < .001). Asymptotic chi2 tests showed that inclusion of DTA score
significantly improved fit of both baseline and longitudinal linear mixed models
in the prediction of pulmonary function (P < .001 for both). Conclusion When
compared with semiquantitative visual assessment and CT histogram-based
measurements, DTA score provides additional information that can be used to
predict diminished function. Automatic quantification of lung fibrosis at CT
yields an index of severity that correlates with visual assessment and functional
change in subjects with IPF. (c) RSNA, 2017.
PMID- 28493790
TI - Endometrial Carcinoma: MR Imaging-based Texture Model for Preoperative Risk
Stratification-A Preliminary Analysis.
AB - Purpose To evaluate the associations among mathematical modeling with the use of
magnetic resonance (MR) imaging-based texture features and deep myometrial
invasion (DMI), lymphovascular space invasion (LVSI), and histologic high-grade
endometrial carcinoma. Materials and Methods Institutional review board approval
was obtained for this retrospective study. This study included 137 women with
endometrial carcinomas measuring greater than 1 cm in maximal diameter who
underwent 1.5-T MR imaging before hysterectomy between January 2011 and December
2015. Texture analysis was performed with commercial research software with
manual delineation of a region of interest around the tumor on MR images (T2
weighted, diffusion-weighted, and dynamic contrast material-enhanced images and
apparent diffusion coefficient maps). Areas under the receiver operating
characteristic curve and diagnostic performance of random forest models
determined by using a subset of the most relevant texture features were estimated
and compared with those of independent and blinded visual assessments by three
subspecialty radiologists. Results A total of 180 texture features were extracted
and ultimately limited to 11 features for DMI, 12 for LVSI, and 16 for high-grade
tumor for random forest modeling. With random forest models, areas under the
receiver operating characteristic curve, sensitivity, specificity, accuracy,
positive predictive value, and negative predictive value were estimated at 0.84,
79.3%, 82.3%, 81.0%, 76.7%, and 84.4% for DMI; 0.80, 80.9%, 72.5%, 76.6%, 74.3%,
and 79.4% for LVSI; and 0.83, 81.0%, 76.8%, 78.1%, 60.7%, and 90.1% for high
grade tumor, respectively. Sensitivity, specificity, accuracy, positive
predictive value, and negative predictive value of visual assessment for DMI were
84.5%, 82.3%, 83.2%, 77.7%, and 87.8% (reader 3). Conclusion The mathematical
models that incorporated MR imaging-based texture features were associated with
the presence of DMI, LVSI, and high-grade tumor and achieved equivalent accuracy
to that of subspecialty radiologists for assessment of DMI in endometrial cancers
larger than 1 cm. However, these preliminary results must be interpreted with
caution until they are validated with an independent data set, because the small
sample size relative to the number of features extracted may have resulted in
overfitting of the models. (c) RSNA, 2017 Online supplemental material is
available for this article.
PMID- 28493792
TI - Transthoracic Echocardiography: Pitfalls and Limitations as Delineated at Cardiac
CT and MR Imaging-Erratum.
PMID- 28493791
TI - Recurrent Shoulder Instability in a Young, Active, Military Population and Its
Professional Implications.
AB - BACKGROUND: Shoulder instability is a topic of significant interest within the
sports medicine literature, particularly regarding recurrence rates and the ideal
treatment indications and techniques. Little has been published specifically
addressing the occupational implications of symptomatic recurrent shoulder
instability. HYPOTHESIS: Previous arthroscopic repair will continue to be a
significant predisposing factor for recurrent instability in a young, active
population, and that recurrent instability may have a negative effect on college
graduation and postgraduate occupational selection. STUDY DESIGN: Case series.
LEVEL OF EVIDENCE: Level 4. METHODS: We conducted a retrospective review of
approved medical waivers for surgical treatment of anterior shoulder dislocation
or instability prior to matriculation at the US Military Academy or the US Naval
Academy for the graduating classes of 2010 to 2013. Statistical analysis was
performed to determine the incidence and risk factors for recurrence and to
determine the impact on graduation rate and occupation selection. RESULTS: Fifty
nine patients were evaluated; 34% developed recurrent anterior instability.
Patients with previous arthroscopic repair had a significantly higher incidence
of recurrence (38%, P = 0.044). Recurrent shoulder instability did not
significantly affect graduation rates or self-selected occupation ( P >= 0.05).
CONCLUSION: There is a significant rate of recurrent shoulder instability after
primary surgical repair, particularly among young, active individuals. In
addition, arthroscopic repair resulted in a significantly higher recurrence rate
compared with open repair in our population. Surgical repair for shoulder
instability should not necessarily preclude young individuals from pursuing (or
being considered for) occupations that may place them at greater risk of
recurrence. CLINICAL RELEVANCE: The risk of recurrent instability is greater than
the rate typically described, which may suggest that some subpopulations are at
greater risk than others. A unique data point regarding instability is the effect
on occupation selection.
PMID- 28493794
TI - The Thymus: A Comprehensive Review-Erratum.
PMID- 28493795
TI - Diagnosis and Management of Complications from Percutaneous Biliary Tract
Interventions-Erratum.
PMID- 28493796
TI - Traumatic Rib Injury: Patterns, Imaging Pitfalls, Complications, and Treatment
Erratum.
PMID- 28493797
TI - Invited Commentary on "Radiologic-Pathologic Correlation of Primary and Secondary
Cardiomyopathies".
PMID- 28493798
TI - Nontraumatic Lesions of the Scalp: Practical Approach to Imaging Diagnosis:
Neurologic/Head and Neck Imaging.
PMID- 28493800
TI - IASLC/ITMIG Staging System and Lymph Node Map for Thymic Epithelial Neoplasms.
AB - Thymic epithelial neoplasms are rare malignancies that arise from the thymus and
include thymoma, thymic carcinoma, and thymic neuroendocrine tumors. At least 15
different stage classifications have been proposed for thymic epithelial
neoplasms and used to varying degrees in clinical practice, many of which have
been constructed from small groups of patients. Traditionally, the Masaoka and
Masaoka-Koga staging systems have been the schemes most commonly employed, and
the latter has been recommended for use by the International Thymic Malignancy
Interest Group (ITMIG). An official, consistent stage classification system has
recently been recognized by the American Joint Committee on Cancer (AJCC) and the
Union for International Cancer Control (UICC), which are responsible for defining
stage classifications for neoplasms. To establish this stage classification
system, the International Association for the Study of Lung Cancer (IASLC) and
ITMIG amassed a large retrospective database and evaluated this group of cases to
develop proposals for the eighth edition of the stage classification manuals. For
this endeavor, IASLC provided funding and statistical analysis and ITMIG provided
the involvement of the clinicians and researchers actively participating in the
study of thymic epithelial neoplasms. To accomplish this, a Thymic Domain of the
Staging and Prognostic Factors Committee (TD-SPFC) was established to formulate
the rationale, methodology, and definitions of this tumor-node-metastasis (TNM)
staging system, which is presented in this article. (c) RSNA, 2017.
PMID- 28493799
TI - Shear-Wave Elastography: Basic Physics and Musculoskeletal Applications.
AB - In the past 2 decades, sonoelastography has been progressively used as a tool to
help evaluate soft-tissue elasticity and add to information obtained with
conventional gray-scale and Doppler ultrasonographic techniques. Recently
introduced on clinical scanners, shear-wave elastography (SWE) is considered to
be more objective, quantitative, and reproducible than compression
sonoelastography with increasing applications to the musculoskeletal system. SWE
uses an acoustic radiation force pulse sequence to generate shear waves, which
propagate perpendicular to the ultrasound beam, causing transient displacements.
The distribution of shear-wave velocities at each pixel is directly related to
the shear modulus, an absolute measure of the tissue's elastic properties. Shear
wave images are automatically coregistered with standard B-mode images to provide
quantitative color elastograms with anatomic specificity. Shear waves propagate
faster through stiffer contracted tissue, as well as along the long axis of
tendon and muscle. SWE has a promising role in determining the severity of
disease and treatment follow-up of various musculoskeletal tissues including
tendons, muscles, nerves, and ligaments. This article describes the basic
ultrasound physics of SWE and its applications in the evaluation of various
traumatic and pathologic conditions of the musculoskeletal system. (c)RSNA, 2017.
PMID- 28493801
TI - Imaging of Hydatid Disease with a Focus on Extrahepatic Involvement.
AB - Hydatid disease (HD) is a parasitic infection caused by the larvae of a tapeworm
that is endemic to many regions around the world-South America, Africa, and Asia,
in particular. Humans are infected as intermediate hosts in the parasite's life
cycle; thus, HD can be seen in persons living in areas where animal husbandry is
practiced. However, owing to the varied patterns of migration and immigration
during the past several decades, HD can be diagnosed in individuals living
anywhere. The liver is the most common organ involved, with hepatic HD accounting
for the majority of published cases. However, HD can affect multiple organs and
tissues other than the liver, including the spleen, kidneys, lungs, heart,
peritoneum, muscles, and brain. Knowledge of the route of spread, clinical
findings at presentation, and possible complications involving each extrahepatic
location can be useful for the radiologist when evaluating imaging findings in
patients suspected of having HD. The ultrasonographic, computed tomographic, and
magnetic resonance imaging findings of extrahepatic hydatid lesions frequently
simulate those of hepatic HD, as long as rupture, bleeding, and/or superimposed
bacterial infection has not occurred. Specific features of HD seen at different
extrahepatic sites can help tailor the diagnosis. The differential diagnoses that
can mimic HD at every nonhepatic location should be considered, as many of these
entities are common, especially in nonendemic areas. (c)RSNA, 2017.
PMID- 28493802
TI - Placental Imaging: Normal Appearance with Review of Pathologic Findings.
AB - The placenta plays a crucial role throughout pregnancy, and its importance may be
overlooked during routine antenatal imaging evaluation. Detailed systematic
assessment of the placenta at ultrasonography (US), the standard imaging
examination during pregnancy, is important. Familiarity with the normal and
abnormal imaging appearance of the placenta along with the multimodality and
methodical approach for evaluation of its related abnormalities is necessary, so
that radiologists can alert clinicians regarding appropriate prompt management
decisions. This will potentially decrease fetal and maternal morbidity and
mortality. This article reviews early placental formation and the expected
imaging appearance of the placenta during pregnancy, as well as variations in its
morphology. It also discusses various placental diseases and their potential
clinical consequences. Placental pathologic conditions include abnormalities of
placental size, cord insertion, placental and cord location, and placental
adherence. Other conditions such as bleeding in and around the placenta, as well
as trophoblastic and nontrophoblastic tumors of the placenta, are also discussed.
US with Doppler imaging is the initial imaging modality of choice for placental
evaluation. Magnetic resonance (MR) imaging is reserved for equivocal cases or
when additional information is needed. Computed tomography (CT) has a limited
role in evaluation of placental abnormalities because of the ionizing radiation
exposure and the relatively limited assessment of the placenta; however, CT can
provide important information in specific circumstances, particularly evaluation
of trauma and staging of choriocarcinoma. This article also addresses recent
techniques and updates in placental imaging, including elastography, diffusion
weighted MR imaging, and blood oxygen level-dependent (BOLD) MR imaging. These
advanced imaging techniques may provide additional information in evaluation of
abnormal placental adherence and new insights into placental pathophysiology in
selected patients. Online supplemental material is available for this article.
(c)RSNA, 2017.
PMID- 28493803
TI - Soft-Tissue Sarcomas of the Abdomen and Pelvis: Radiologic-Pathologic Features,
Part 2-Uncommon Sarcomas.
AB - Soft-tissue sarcomas occurring in the abdomen and pelvis are an uncommon but
important group of malignancies. Recent changes to the World Health Organization
classification of soft-tissue tumors include the movement of gastrointestinal
stromal tumors (GISTs) into the soft-tissue tumor classification. GIST is the
most common intraperitoneal sarcoma. Liposarcoma is the most common
retroperitoneal sarcoma, and leiomyosarcoma is the second most common. GIST,
liposarcoma, and leiomyosarcoma account for the majority of sarcomas encountered
in the abdomen and pelvis and are discussed in part 1 of this article.
Undifferentiated pleomorphic sarcoma (previously called malignant fibrous
histiocytoma), dermatofibrosarcoma protuberans, solitary fibrous tumor, malignant
peripheral nerve sheath tumor, rhabdomyosarcoma, extraskeletal chondro-osseous
sarcomas, vascular sarcomas, and sarcomas of uncertain differentiation uncommonly
arise in the abdomen and pelvis and the abdominal wall. Although these lesions
are rare sarcomas and their imaging features overlap, familiarity with the
locations where they occur and their imaging features is important so they can be
diagnosed accurately. The anatomic location and clinical history are important
factors in the differential diagnosis of these lesions because metastasis, more
common sarcomas, borderline fibroblastic proliferations (such as desmoid tumors),
and endometriosis have imaging findings that overlap with those of these uncommon
sarcomas. In this article, the clinical, pathologic, and imaging findings of
uncommon soft-tissue sarcomas of the abdomen and pelvis and the abdominal wall
are reviewed, with an emphasis on their differential diagnosis.
PMID- 28493804
TI - Hereditary Renal Cystic Disorders: Imaging of the Kidneys and Beyond.
AB - The purpose of this article is to review the hereditary renal cystic diseases
that can manifest in children and adults, with specific attention to pathogenesis
and imaging features. Various common and uncommon hereditary renal cystic
diseases are reviewed in terms of their underlying etiology, including the
involved genetic mutations and the affected proteins and cellular structures.
Focus is placed on the morphologic findings in each condition and the features
that distinguish one disorder from another. The two most common categories of
hereditary renal cystic disease are (a) the ciliopathic disorders, which are
related to mutations affecting the primary cilia (called "ciliopathies"), and (b)
the phakomatoses. Autosomal dominant polycystic kidney disease, autosomal
recessive polycystic kidney disease, and the "medullary cystic disease complex"
are all ciliopathies but have different phenotypes. Tuberous sclerosis complex
and the associated "contiguous gene syndrome," as well as von Hippel-Lindau
syndrome, are phakomatoses that can manifest with cystic renal lesions but have
uniquely different extrarenal manifestations. Finally, DICER1 mutations can
manifest with renal cystic lesions (typically, cystic nephromas) in patients
predisposed to other malignancies in the chest, ovaries, and thyroid. Although
some overlap exists in the appearance of the renal cysts associated with each of
these diseases, there are clear morphologic differences (eg, cyst size, location,
and complexity) that are emphasized in this review. To improve patient outcomes,
it is important for the radiologist to recognize the various hereditary renal
cystic diseases so that a correct diagnosis is assigned and so that the patient
is adequately evaluated and followed up. (c)RSNA, 2017.
PMID- 28493805
TI - Creating Three-dimensional Printed Models of Acetabular Fractures for Use as
Educational Tools.
AB - Acetabular fractures are frequently encountered in some clinical practices, and
the precise classification of these fractures greatly influences treatments and
outcomes. The authors identified the need for an educational aid when teaching
acetabular fracture classifications, given the complex spatial anatomy and the
nonintuitive classification system that is commonly used. Three-dimensional ( 3D
three-dimensional ) printing is an evolving technique that has applications as an
educational aid, providing the student with a tangible object to interact with
and learn from. In this article, the authors review their experience creating 3D
three-dimensional printed models of the hip for educational purposes. Their goal
was to create 3D three-dimensional printed models for use as educational aids
when teaching acetabular fracture classifications. Complex cases involving a
combination of fracture types, subtle nondisplaced fractures, and/or fractures
with associated osteopenia or artifacts were excluded. The selected computed
tomographic (CT) scans were loaded into a medical 3D three-dimensional volume
rendering program, and a 3D three-dimensional volumetric model was created.
Standard Tessellation Language ( STL Standard Tessellation Language ) files were
then exported to STL Standard Tessellation Language model-editing software and
edited to retain only the involved hemipelvis. In some cases, the proximal femur
and ipsilateral hemisacrum may be included to emphasize hip alignment or
disruption of the force transfer. Displaced fracture fragments can be printed as
separate segments or a single unit after the addition of struts. Printing was
performed by using an additive manufacturing principle, with approximately 36-48
hours needed for printing, postprocessing, and drying. The cost to print a 1:1
scale model was approximately $100-$200, depending on the amount of plastic
material used. These models can then be painted according to the two-column
theory regarding acetabular fractures. (c)RSNA, 2017.
PMID- 28493806
TI - Pediatric Benign Bone Tumors: What Does the Radiologist Need to Know?: Pediatric
Imaging.
PMID- 28493807
TI - What Is Actually Affected by the Scrambling of Objects When Localizing the
Lateral Occipital Complex?
AB - The lateral occipital complex (LOC), the cortical region critical for shape
perception, is localized with fMRI by its greater BOLD activity when viewing
intact objects compared with their scrambled versions (resembling texture).
Despite hundreds of studies investigating LOC, what the LOC localizer
accomplishes-beyond distinguishing shape from texture-has never been resolved. By
independently scattering the intact parts of objects, the axis structure defining
the relations between parts was no longer defined. This led to a diminished BOLD
response, despite the increase in the number of independent entities (the parts)
produced by the scattering, thus indicating that LOC specifies interpart
relations, in addition to specifying the shape of the parts themselves. LOC's
sensitivity to relations is not confined to those between parts but is also
readily apparent between objects, rendering it-and not subsequent "place" areas
as the critical region for the representation of scenes. Moreover, that these
effects are witnessed with novel as well as familiar intact objects and scenes
suggests that the relations are computed on the fly, rather than being retrieved
from memory.
PMID- 28493808
TI - Prestimulus Alpha Oscillations and the Temporal Sequencing of Audiovisual Events.
AB - Perceiving the temporal order of sensory events typically depends on
participants' attentional state, thus likely on the endogenous fluctuations of
brain activity. Using magnetoencephalography, we sought to determine whether
spontaneous brain oscillations could disambiguate the perceived order of auditory
and visual events presented in close temporal proximity, that is, at the
individual's perceptual order threshold (Point of Subjective Simultaneity [PSS]).
Two neural responses were found to index an individual's temporal order
perception when contrasting brain activity as a function of perceived order
(i.e., perceiving the sound first vs. perceiving the visual event first) given
the same physical audiovisual sequence. First, average differences in prestimulus
auditory alpha power indicated perceiving the correct ordering of audiovisual
events irrespective of which sensory modality came first: a relatively low alpha
power indicated perceiving auditory or visual first as a function of the actual
sequence order. Additionally, the relative changes in the amplitude of the
auditory (but not visual) evoked responses were correlated with participant's
correct performance. Crucially, the sign of the magnitude difference in
prestimulus alpha power and evoked responses between perceived audiovisual orders
correlated with an individual's PSS. Taken together, our results suggest that
spontaneous oscillatory activity cannot disambiguate subjective temporal order
without prior knowledge of the individual's bias toward perceiving one or the
other sensory modality first. Altogether, our results suggest that, under high
perceptual uncertainty, the magnitude of prestimulus alpha (de)synchronization
indicates the amount of compensation needed to overcome an individual's prior in
the serial ordering and temporal sequencing of information.
PMID- 28493809
TI - Buildings, Beauty, and the Brain: A Neuroscience of Architectural Experience.
AB - A burgeoning interest in the intersection of neuroscience and architecture
promises to offer biologically inspired insights into the design of spaces. The
goal of such interdisciplinary approaches to architecture is to motivate
construction of environments that would contribute to peoples' flourishing in
behavior, health, and well-being. We suggest that this nascent field of
neuroarchitecture is at a pivotal point in which neuroscience and architecture
are poised to extend to a neuroscience of architecture. In such a research
program, architectural experiences themselves are the target of neuroscientific
inquiry. Here, we draw lessons from recent developments in neuroaesthetics to
suggest how neuroarchitecture might mature into an experimental science. We
review the extant literature and offer an initial framework from which to
contextualize such research. Finally, we outline theoretical and technical
challenges that lie ahead.
PMID- 28493810
TI - Rapid Statistical Learning Supporting Word Extraction From Continuous Speech.
AB - The identification of words in continuous speech, known as speech segmentation,
is a critical early step in language acquisition. This process is partially
supported by statistical learning, the ability to extract patterns from the
environment. Given that speech segmentation represents a potential bottleneck for
language acquisition, patterns in speech may be extracted very rapidly, without
extensive exposure. This hypothesis was examined by exposing participants to
continuous speech streams composed of novel repeating nonsense words. Learning
was measured on-line using a reaction time task. After merely one exposure to an
embedded novel word, learners demonstrated significant learning effects, as
revealed by faster responses to predictable than to unpredictable syllables.
These results demonstrate that learners gained sensitivity to the statistical
structure of unfamiliar speech on a very rapid timescale. This ability may play
an essential role in early stages of language acquisition, allowing learners to
rapidly identify word candidates and "break in" to an unfamiliar language.
PMID- 28493811
TI - Pooled Analysis of Individual Patient Data on Concurrent Chemoradiotherapy for
Stage III Non-Small-Cell Lung Cancer in Elderly Patients Compared With Younger
Patients Who Participated in US National Cancer Institute Cooperative Group
Studies.
AB - Purpose Concurrent chemoradiotherapy is standard treatment for patients with
stage III non-small-cell lung cancer. Elderly patients may experience increased
rates of adverse events (AEs) or less benefit from concurrent chemoradiotherapy.
Patients and Methods Individual patient data were collected from 16 phase II or
III trials conducted by US National Cancer Institute-supported cooperative groups
of concurrent chemoradiotherapy alone or with consolidation or induction
chemotherapy for stage III non-small-cell lung cancer from 1990 to 2012. Overall
survival (OS), progression-free survival, and AEs were compared between patients
age >= 70 (elderly) and those younger than 70 years (younger). Unadjusted and
adjusted hazard ratios (HRs) for survival time and CIs were estimated by single
predictor and multivariable frailty Cox models. Unadjusted and adjusted odds
ratio (ORs) for AEs and CIs were obtained from single-predictor and multivariable
generalized linear mixed-effect models. Results A total of 2,768 patients were
classified as younger and 832 as elderly. In unadjusted and multivariable models,
elderly patients had worse OS (HR, 1.20; 95% CI, 1.09 to 1.31 and HR, 1.17; 95%
CI, 1.07 to 1.29, respectively). In unadjusted and multivariable models, elderly
and younger patients had similar progression-free survival (HR, 1.01; 95% CI,
0.93 to 1.10 and HR, 1.00; 95% CI, 0.91 to 1.09, respectively). Elderly patients
had a higher rate of grade >= 3 AEs in unadjusted and multivariable models (OR,
1.35; 95% CI, 1.07 to 1.70 and OR, 1.38; 95% CI, 1.10 to 1.74, respectively).
Grade 5 AEs were significantly higher in elderly compared with younger patients
(9% v 4%; P < .01). Fewer elderly compared with younger patients completed
treatment (47% v 57%; P < .01), and more discontinued treatment because of AEs
(20% v 13%; P < .01), died during treatment (7.8% v 2.9%; P < .01), and refused
further treatment (5.8% v 3.9%; P = .02). Conclusion Elderly patients in
concurrent chemoradiotherapy trials experienced worse OS, more toxicity, and had
a higher rate of death during treatment than younger patients.
PMID- 28493813
TI - Further Advances in the Management of Anaplastic Lymphoma Kinase-Mutated Non
Small-Cell Lung Cancer.
PMID- 28493814
TI - Obesity and Modifiable Cardiovascular Disease Risk Factors Among Chinese
Americans in New York City, 2009-2012.
AB - We used the Racial and Ethnic Approaches to Community Health Across the US (REACH
US) Risk Factor Survey from 2009 through 2012 to examine the association between
body mass index (BMI, calculated as kg/m2) and 3 cardiovascular disease risk
factors among Chinese Americans in New York City. We used traditional BMI cut
points and cut points modified for the Asian population. Compared with
normal/underweight Chinese American adults (BMI <23.0), obese Chinese American
adults (BMI >=27.5) had significantly higher odds of having each risk factor in
fully adjusted logistic regression models: diabetes (odds ratio [OR], 4.2; 95%
confidence interval [CI], 2.8-6.2), high blood pressure (OR, 5.5; 95% CI, 3.9
7.7), and high cholesterol (OR, 1.7; 95% CI, 1.2-2.4). Regression results were
similar across BMI definitions, suggesting that both BMI categorizations should
be considered in CVD research among Chinese Americans.
PMID- 28493815
TI - The biology of JC polyomavirus.
AB - JC polyomavirus (JCPyV) is the causative agent of a fatal central nervous system
demyelinating disease known as progressive multifocal leukoencephalopathy (PML).
PML occurs in people with underlying immunodeficiency or in individuals being
treated with potent immunomodulatory therapies. JCPyV is a DNA tumor virus with a
double-stranded DNA genome and encodes a well-studied oncogene, large T antigen.
Its host range is highly restricted to humans and only a few cell types support
lytic infection in vivo or in vitro. Its oncogenic potential in humans has not
been firmly established and the international committee on oncogenic viruses
lists JCPyV as possibly carcinogenic. Significant progress has been made in
understanding the biology of JCPyV and here we present an overview of the field
and discuss some important questions that remain unanswered.
PMID- 28493812
TI - Treatment Decision Regret Among Long-Term Survivors of Localized Prostate Cancer:
Results From the Prostate Cancer Outcomes Study.
AB - Purpose To determine the demographic, clinical, decision-making, and quality-of
life factors that are associated with treatment decision regret among long-term
survivors of localized prostate cancer. Patients and Methods We evaluated men who
were age <= 75 years when diagnosed with localized prostate cancer between
October 1994 and October 1995 in one of six SEER tumor registries and who
completed a 15-year follow-up survey. The survey obtained demographic,
socioeconomic, and clinical data and measured treatment decision regret, informed
decision making, general- and disease-specific quality of life, health worry,
prostate-specific antigen (PSA) concern, and outlook on life. We used
multivariable logistic regression analyses to identify factors associated with
regret. Results We surveyed 934 participants, 69.3% of known survivors. Among the
cohort, 59.1% had low-risk tumor characteristics (PSA < 10 ng/mL and Gleason
score < 7), and 89.2% underwent active treatment. Overall, 14.6% expressed
treatment decision regret: 8.2% of those whose disease was managed
conservatively, 15.0% of those who received surgery, and 16.6% of those who
underwent radiotherapy. Factors associated with regret on multivariable analysis
included reporting moderate or big sexual function bother (reported by 39.0%; OR,
2.77; 95% CI, 1.51 to 5.0), moderate or big bowel function bother (reported by
7.7%; OR, 2.32; 95% CI, 1.04 to 5.15), and PSA concern (mean score 52.8; OR, 1.01
per point change; 95% CI, 1.00 to 1.02). Increasing age at diagnosis and report
of having made an informed treatment decision were inversely associated with
regret. Conclusion Regret was a relatively infrequently reported outcome among
long-term survivors of localized prostate cancer; however, our results suggest
that better informing men about treatment options, in particular, conservative
treatment, might help mitigate long-term regret. These findings are timely for
men with low-risk cancers who are being encouraged to consider active
surveillance.
PMID- 28493816
TI - Sample types applied for molecular diagnosis of therapeutic management of
advanced non-small cell lung cancer in the precision medicine.
AB - In this era of precision medicine, molecular biology is becoming increasingly
significant for the diagnosis and therapeutic management of non-small cell lung
cancer. The specimen as the primary element of the whole testing flow is
particularly important for maintaining the accuracy of gene alteration testing.
Presently, the main sample types applied in routine diagnosis are tissue and
cytology biopsies. Liquid biopsies are considered as the most promising
alternatives when tissue and cytology samples are not available. Each sample type
possesses its own strengths and weaknesses, pertaining to the disparity of
sampling, preparation and preservation procedures, the heterogeneity of inter- or
intratumors, the tumor cellularity (percentage and number of tumor cells) of
specimens, etc., and none of them can individually be a "one size to fit all".
Therefore, in this review, we summarized the strengths and weaknesses of
different sample types that are widely used in clinical practice, offered
solutions to reduce the negative impact of the samples and proposed an optimized
strategy for choice of samples during the entire diagnostic course. We hope to
provide valuable information to laboratories for choosing optimal clinical
specimens to achieve comprehensive functional genomic landscapes and formulate
individually tailored treatment plans for NSCLC patients that are in advanced
stages.
PMID- 28493817
TI - The relationship between anxiety, depression and risk behaviors in adolescents.
AB - Aim Adolescence is a developmental period often associated with high-risk
behaviors. While some risk-taking behavior is considered normative in
adolescents, research has indicated an association between risky behaviors and
mental ill-health. The current research aimed to examine the relationship between
anxiety and depression with the occurrence of high-risk behaviors in adolescents
and also determine the predictive factors of these main variables. Methods A
descriptive, cross-sectional, correlational design was used to collect data from
399 adolescents between the ages of 14 and 19 residing in Qazvin, Iran using the
Revised Child Anxiety and Depression Scale (RCADS) and the Iranian Adolescents
Risk-taking Scale (IARS) between the period of October and November 2015. Data
analysis included descriptive and inferential statistics powered by SPSS (v. 23).
Results Mean scores for anxiety, depression and risky behaviors were 37.70 +/-
21.11 and 80.76 +/- 31.30, respectively. Participants' frequency of suicidal
thoughts (beta = 0.126, p < 0.05) positively predicted anxiety and depression,
while age (beta = -0.126, p < 0.01) and self-confidence (beta = -0.307, p <
0.001) negatively predicted anxiety and depression. Moreover, having friends that
smoke (beta = 0.366, p < 0.001), suicidal thoughts (beta = 0.127, p < 0.01), and
the strength of suicidal thoughts (beta = 0.100, p < 0.05) were positive
predictors of occurrence of risky behaviors. Furthermore, religious belief (beta
= -0.204, p < 0.001) negatively predicted occurrence of risky behaviors in
Iranian adolescents. Male respondents were more likely to have higher level of
occurrence of risky behaviors than females (beta = -0.193, p < 0.001). Conclusion
Findings of the present study suggest that anxiety and depression positively and
significantly predict the occurrence of risky behaviors in addition to having
friends that smoke, suicidal thoughts, and strong suicidal thinking. The
implications of these findings have relevance for screening, prevention, and
treatment interventions targeting mental health in adolescents.
PMID- 28493818
TI - Group Tests for High-dimensional Failure Time Data with the Additive Hazards
Models.
AB - Statistical analysis of high-dimensional data has been attracting more and more
attention due to the abundance of such data in various fields such as genetic
studies or genomics and the existence of many interesting topics. Among them, one
is the identification of a gene or genes that have significant effects on the
occurrence of or are significantly related to a certain disease. In this paper,
we will discuss such a problem that can be formulated as a group test or testing
a group of variables or coefficients when one faces right-censored failure time
response variable. For the problem, we develop a corrected variance reduced
partial profiling (CVRPP) linear regression model and a likelihood ratio test
procedure when the failure time of interest follows the additive hazards model.
The numerical study suggests that the proposed method works well in practical
situations and gives better performance than the existing one. An illustrative
example is provided.
PMID- 28493819
TI - The choice of freely preferred cadence by trained nonprofessional cyclists may
not be characterized by mechanical efficiency.
AB - BACKGROUND: Most cycling studies involve professional cyclists. Because training
may affect riding style, it is of interest to determine the physiological basis
for the personal choice of cycling cadence in nonprofessional cyclists. METHODS:
Eleven nonprofessional (5.2+/-1.7-year-riding experience) male road cyclists,
aged 35.0+/-11.0 years, underwent four separate laboratory test sessions. The
first two sessions included habituation, anthropometry, VO2max,$?dot
V{{?text{O}}_{?text{2}}}{?text{max}},$ and lactate threshold (LaTH) measurements.
Freely preferred cadence at LaTH was determined during the second session (mean+/
SD=94.7+/-2.9 rev.min-1). During the third and fourth sessions participants
performed LaTH tests at 60 and 95 rev.min-1 in a randomized order, with power
output (PO) increments of 25 W every 4 min, up to ~90% of VO2max.$?dot
V{{?text{O}}_{?text{2}}}{?text{max}}{?text{.}}$ Results: VO2,$?dot
V{{?text{O}}_{?text{2}}},$ expired ventilation (VE),$({?dot V_E}),$ blood lactate
(La), and calculated net mechanical efficiency (MEnet) rose with increased PO. At
95 rev.min-1, VO2, VE,$?dot V{{?text{O}}_2},{?text{ }}{?dot V_{?text{E}}},$ and
La were significantly higher than at 60 rev.min-1 at all POs. MEnet at 95 rev.min
1 was lower than at 60 rev.min-1. Mean PO attained at LaTh did not differ
significantly between 60 and 95 rev.min-1 (220.9+/-29.0 and 214.5+/-9.2 W,
respectively). La values at LaTH were higher at 95 rev.min-1 than at 60 rev.min-1
(3.01+/-0.17 vs. 2.10+/-0.13 mM, p<0.05, respectively). CONCLUSIONS: Our findings
indicate that mechanical and physiological efficiencies may not determine the
choice of cycling cadence by nonprofessional cyclists. This choice may reflect
the need to maintain endurance at the expense of riding at a lower than optimal
riding efficiency.
PMID- 28493820
TI - Deoxyguanosine kinase deficiency: a report of four patients.
AB - BACKGROUND: Hepatic involvement is a common feature in childhood mitochondrial
disorders. Deoxyguanosine kinase (DGUOK) deficiency is one of the mitochondrial
DNA depletion syndromes associated with hepatocerebral syndrome. Hepatic disease
and neurologic dysfunction occurs within weeks after birth. Low birth weight is
one of the common features. This study aims to describe the clinical and
laboratory features of four infants carrying four different pathogenic variants
in the DGUOK gene. CASE PRESENTATION: Common clinical findings were progressive
cholestatic liver failure, hypoglycemia, hypotonia and rotatory nystagmus in our
DGUOK deficiency patients. Lactic acidosis, elevated serum tyrosine and ferritin
levels were the striking laboratory features. Cholestasis, iron deposits,
microvesicular steatosis and fibrosis were the histopathological findings seen in
liver biopsies of two patients. All patients died with multi-organ failure
between the ages of 42 days and 6 months. CONCLUSIONS: While neurologic findings
may occur later in the course of the disease, elevated serum tyrosine levels may
alert the physicians to a DGUOK deficiency in a baby with hepatopathy in the
presence of the mentioned signs. Early diagnosis is important not only for
genetic counseling but also for a possible liver transplantation.
PMID- 28493821
TI - Multicentric studies of the fetal neurobehavior by KANET test.
AB - Assessment of fetal neurobehavior and detection of neurological impairment
prenatally has been a great challenge in perinatal medicine. The evolution of
four-dimensional (4D) ultrasound not only enabled a better visualization of fetal
anatomy but also allowed the study of fetal behavior in real time. Kurjak
Antenatal Neurodevelopmental Test (KANET) was developed for the assessment of
fetal neurobehavior and the detection of neurological disorders, based on the
assessment of the fetus by application of 4D ultrasound in the same way that a
neonate is assessed postnatally. KANET is a method that has been applied for the
past 10 years and studies show that it is a strong diagnostic tool and can be
introduced into everyday clinical practice. We present all data from studies
performed up to now on KANET.
PMID- 28493822
TI - Diagnosis of fetal syndromes by three- and four-dimensional ultrasound: is there
any improvement?
AB - With all of our present knowledge, high technology diagnostic equipment,
electronic databases and other available supporting resources, detection of fetal
syndromes is still a challenge for healthcare providers in prenatal as well as in
the postnatal period. Prenatal diagnosis of fetal syndromes is not
straightforward, and it is a difficult puzzle that needs to be assembled and
solved. Detection of one anomaly should always raise a suspicion of the existence
of more anomalies, and can be a trigger to investigate further and raise
awareness of possible syndromes. Highly specialized software systems for three-
and four-dimensional ultrasound (3D/4D US) enabled detailed depiction of fetal
anatomy and assessment of the dynamics of fetal structural and functional
development in real time. With recent advances in 3D/4D US technology, antenatal
diagnosis of fetal anomalies and syndromes shifted from the 2nd to the 1st
trimester of pregnancy. It is questionable what can and should be done after the
prenatal diagnosis of fetal syndrome. The 3D and 4D US techniques improved
detection accuracy of fetal abnormalities and syndromes from early pregnancy
onwards. It is not easy to make prenatal diagnosis of fetal syndromes, so tools
which help like online integrated databases are needed to increase diagnostic
precision. The aim of this paper is to present the possibilities of different US
techniques in the detection of some fetal syndromes prenatally.
PMID- 28493848
TI - Investigating multi-objective fluence and beam orientation IMRT optimization.
AB - Radiation Oncology treatment planning requires compromises to be made between
clinical objectives that are invariably in conflict. It would be beneficial to
have a 'bird's-eye-view' perspective of the full spectrum of treatment plans that
represent the possible trade-offs between delivering the intended dose to the
planning target volume (PTV) while optimally sparing the organs-at-risk (OARs).
In this work, the authors demonstrate Pareto-aware radiotherapy evolutionary
treatment optimization (PARETO), a multi-objective tool featuring such bird's-eye
view functionality, which optimizes fluence patterns and beam angles for
intensity-modulated radiation therapy (IMRT) treatment planning. The problem of
IMRT treatment plan optimization is managed as a combined monolithic problem,
where all beam fluence and angle parameters are treated equally during the
optimization. To achieve this, PARETO is built around a powerful multi-objective
evolutionary algorithm, called Ferret, which simultaneously optimizes multiple
fitness functions that encode the attributes of the desired dose distribution for
the PTV and OARs. The graphical interfaces within PARETO provide useful
information such as: the convergence behavior during optimization, trade-off
plots between the competing objectives, and a graphical representation of the
optimal solution database allowing for the rapid exploration of treatment plan
quality through the evaluation of dose-volume histograms and isodose
distributions. PARETO was evaluated for two relatively complex clinical cases, a
paranasal sinus and a pancreas case. The end result of each PARETO run was a
database of optimal (non-dominated) treatment plans that demonstrated trade-offs
between the OAR and PTV fitness functions, which were all equally good in the
Pareto-optimal sense (where no one objective can be improved without worsening at
least one other). Ferret was able to produce high quality solutions even though a
large number of parameters, such as beam fluence and beam angles, were included
in the optimization.
PMID- 28493839
TI - Hypoxia inducible factors in hepatocellular carcinoma.
AB - Hepatocellular carcinoma is one of the most prevalent and lethal cancers with
limited therapeutic options. Pathogenesis of this disease involves tumor hypoxia
and the activation of hypoxia inducible factors. In this review, we describe the
current understanding of hypoxia signaling pathway and summarize the expression,
function and target genes of hypoxia inducible factors in hepatocellular
carcinoma. We also highlight the recent progress in hypoxia-targeted therapeutic
strategies in hepatocellular carcinoma and discuss further the future efforts for
the study of hypoxia and/or hypoxia inducible factors in this deadly disease.
PMID- 28493842
TI - Mesenchymal stem cell infiltration during neoplastic transformation of the human
prostate.
AB - Mesenchymal Stem Cells (MSCs) have been identified in prostate cancer, raising
the critical question of their physical and temporal source. Therefore, MSCs were
quantified and characterized in benign and malignant prostate tissue representing
different disease states and a wide range of age groups from fetal development
through adult death using analytical and functional methodologies. In contrast to
lineage-restricted Mesenchymal Progenitor Cells (MPCs) found in normal prostate
tissue, MSCs with tri-lineage differentiation potential (adipogenesis,
osteogenesis, and chondrogenesis) are identified in prostate tissue from a subset
of men with prostate cancer, consistent with an influx of more stem-like
progenitors (i.e. MSCs) from the bone marrow. Additionally, prostate tissue from
a subset of these patients is highly enriched in MSCs, suggesting their
enumeration may have prognostic value for identifying men with aggressive
disease. This influx is an ongoing process continuing throughout disease
progression as documented by the presence of MSCs in metastatic lesions from
multiple organ sites harvested at the time of death in metastatic castration
resistant prostate cancer (mCRPC) patients. This infiltration of MSCs from
systemic circulation provides the rationale for their use as a cell-based vector
to deliver therapeutic agents.
PMID- 28493849
TI - Effects of pressure variation and atrial fibrillation on CardioMEMSTM HF measured
pulmonary artery diastolic pressure: comparison of device-averaged and visually
inspected waveforms.
AB - OBJECTIVE: Heart failure (HF) management guided by implantable hemodynamic
monitoring reduces hospitalization rates. Hemodynamic data from the CardioMEMSTM
HF system includes device-averaged pulmonary artery pressures (PAP) and heart
rate. Agreement of device-averaged values compared to the standard method of
visual inspection of pressure waveforms at end-expiration is unknown. We
evaluated the agreement between device-averaged and visually inspected end
expiratory PAP. APPROACH: Twenty-one patients implanted with the CardioMEMSTM HF
system were evaluated. Eight-hundred twenty-three PAP waveforms from the Merlin
remote monitoring website were visually inspected and pulmonary artery systolic
pressure (PASP) and pulmonary artery diastolic pressure (PADP) at end-expiration
were recorded. Waveforms were evaluated for pressure variation (PV), defined as
the difference between highest and lowest PASP measurement of ?20 mmHg. Bland
Altman analysis quantified differences between device-averaged and visually
inspected waveforms. MAIN RESULTS: All patients were NYHA functional class III,
mean age was 67 +/- 15 years and 15 (71%) had AF. Bland-Altman analysis of all
waveforms revealed a mean-difference in PADP of -1.4 mmHg, indicating that
visually inspected values were higher than device-averaged values. For PV ?20
mmHg, this value increased to -2.8 mmHg. The mean-difference comparing waveforms
from patients with or without AF was -1.3 and -1.6 mmHg, respectively. The 95%
limits of agreement were >50% wider for waveforms from patients with versus
without AF (10.3 versus 6.7 mmHg). SIGNIFICANCE: There is good agreement between
device-averaged and visually inspected waveforms when pressure variation is <20
mmHg and for patients without atrial fibrillation.
PMID- 28493850
TI - Importance of endogenous extracellular matrix in biomechanical properties of
human skin model.
AB - The physical and mechanical properties of cells modulate their behavior such
proliferation rate, migration and extracellular matrix remodeling. In order to
study cell behavior in a tissue-like environment in vitro, it is of utmost
importance to develop biologically and physically relevant 3D cell models. Here,
we characterized the physical properties of a single cell type growing in
configurations of increasing complexity. From one human skin biopsy, primary
dermal fibroblasts were isolated and seeded to give monolayer (2D model),
spheroid (3D model poor in extracellular matrix) and tissue-engineered cell sheet
(3D model rich in endogenous extracellular matrix). Living native human dermis
tissue was used as a gold standard. Nanomechanical and viscoelastic properties at
the cell scale were measured by atomic force microscopy (AFM) while biphoton
microscopy allowed collagen detection by second harmonic generation and scanning
electron microscopy helped in model morphological characterization. In all
models, fibroblasts presented a similar typical elongated cell shape, with a
cytoskeleton well-arranged along the long axis of the cell. However, elastic
moduli of the tissue-engineered cell sheet and native dermis tissue were similar
and statistically lower than monolayer and spheroid models. We successfully
carried out AFM force measurements on 3D models such as spheroids and tissue
engineered cell sheets, as well as on living native human tissue. We demonstrated
that a tissue-engineered dermal model recapitulates the mechanical properties of
human native dermal tissue unlike the classically used monolayer and spheroid
models. Furthermore, we give statistical evidence to indicate a correlation
between cell mechanical properties and the presence of collagens in the models
studied.
PMID- 28493852
TI - Notes from the Field: Severe Human Metapneumovirus Infections - North Dakota,
2016.
PMID- 28493851
TI - Impedimetric Analysis of the Effect of Decellularized Porcine Heart Scaffold on
Human Fibrosarcoma, Endothelial, and Cardiomyocyte Cell Lines.
AB - BACKGROUND Experiments on porcine heart scaffold represent significant assays in
development of immunoneutral materials for cardiac surgery. Characterization of
cell-cell and cell-scaffold interactions is essential to understand the homing
process of cardiac cells into the scaffolds. MATERIAL AND METHODS In the present
study, the highly sensitive and real-time impedimetric technique of xCELLigence
SP was used to monitor cell adhesion, which is the key process of
recellularization in heart scaffolds. Our objectives were: (i) to characterize
the effect of decellularized porcine heart scaffold on cell adhesion of human
cardiovascular cells potentially used in the recellularization process; and (ii)
to investigate cell-extracellular matrix element interactions for building
artificial multi-layer systems, applied as cellular models of recellularization
experiments. Human fibrosarcoma, endothelial, and cardiomyocyte cells were
investigated and the effect of decellularized porcine heart scaffold (HS) and
fibronectin on cell adhesion was examined. Adhesion was quantified as slope of
curves. RESULTS Heart scaffold had neutral effect on cardiomyocytes as well as on
endothelial cells. Adhesion of cardiomyocytes was increased by fibronectin
(1.480+/-0.021) compared to control (0.745+/-0.029). The combination of
fibronectin and HS induced stronger adhesion of cardiomyocytes (2.407+/-0.634)
than fibronectin alone. Endothelial and fibrosarcoma cells showed similarly
strong adhesion profiles with marked enhancer effect by fibronectin. CONCLUSIONS
Decellularized porcine HS does not inhibit adhesion of human cardiovascular cells
at the cell biological level, while fibronectin has strong cell adhesion-inducer
effect, as well as an enhancer effect on activity of HS. Consequently,
decellularized porcine hearts could be used as scaffolds for recellularization
with cardiomyocytes and endothelial cells with fibronectin acting as a regulator,
leading to construction of working bioartificial hearts.
PMID- 28493853
TI - Erratum: Vol. 66, No. 17.
AB - In the report "Vital Signs: Racial Disparities in Age-Specific Mortality Among
Blacks or African Americans - United States, 1999-2015," on page 446, under
"Results," the last sentence of the first paragraph should have read "Among
adults aged >=65 years, the death rate in 2015 relative to that in 1999 declined
27% for blacks and 17% for whites, resulting in a crossover in death rates after
2010, when blacks had lower age-specific death rates than whites."
PMID- 28493855
TI - Announcement: Community Preventive Services Task Force Recommendation for Family
Based Interventions to Increase Physical Activity.
AB - The Community Preventive Services Task Force recently posted new information on
its website: "Physical Activity: Family-Based Interventions." This information is
available at https://www.thecommunityguide.org/findings/physical-activity-family
based-interventions.
PMID- 28493854
TI - State HCV Incidence and Policies Related to HCV Preventive and Treatment Services
for Persons Who Inject Drugs - United States, 2015-2016.
AB - Hepatitis C is associated with more deaths in the United States than 60 other
infectious diseases reported to CDC combined. Despite curative hepatitis C virus
(HCV) therapies and known preventive measures to interrupt transmission, new HCV
infections have increased in recent years (1,2). Injection drug use is the
primary risk factor for new HCV infections (2). One potential strategy to
decrease the prevalence of HCV is to create and strengthen public health laws and
policies aimed specifically at reducing transmission risks among persons who
inject drugs. To evaluate factors affecting access to HCV preventive and
treatment services, CDC assessed state laws governing access to safe injection
equipment and Medicaid policies related to sobriety requirements for approval of
HCV treatment for persons who inject drugs. Acute HCV incidence rates were
obtained from CDC's National Notifiable Disease Surveillance System (NNDSS).
States were categorized based on analysis of laws related to access to clean
needles and syringes and Medicaid HCV treatment policies associated with sobriety
requirements. In 2015, HCV incidence remained high in the United States, with
rates in 17 states exceeding the national average. Three states were determined
to have state laws and Medicaid policies capable of comprehensively preventing
and treating HCV among persons who inject drugs. Opportunities exist for states
to adopt laws and policies that could help increase access to HCV preventive and
treatment services reducing the number of persons at risk for HCV transmission
and disease.
PMID- 28493856
TI - CDC Grand Rounds: Public Health Strategies to Prevent and Treat Strokes.
AB - Worldwide, stroke is the second leading cause of death and a leading cause of
serious long-term disability. In the United States, nearly 800,000 strokes occur
each year; thus stroke is the fifth leading cause of death overall and the fourth
leading cause of death among women (1). Major advances in stroke prevention
through treatment of known risk factors has led to stroke being considered
largely preventable. For example, in the United States, stroke mortality rates
have declined 70% over the past 50 years, in large part because of important
reductions in hypertension, tobacco smoking, and more recently, increased use of
anticoagulation for atrial fibrillation (2,3). Although the reduction in stroke
mortality is recognized as one of the 10 great public health achievements of the
20th century (4), gains can still be made. Approximately 80% of strokes could be
prevented by screening for and addressing known risks with measures such as
improving hypertension control, smoking cessation, diabetes prevention,
cholesterol management, increasing use of anticoagulation for atrial
fibrillation, and eliminating excessive alcohol consumption (5,6).
PMID- 28493858
TI - QuickStats: Age-Adjusted Death Rates* Attributable to Alcohol-Induced Causes,? by
Race/Ethnicity - United States, 1999-2015.
AB - In 2015, mortality from alcohol-induced causes reached the highest rate during
1999-2015 of 9.1 deaths per 100,000 U.S. standard population. Alcohol-induced
death rates for the Hispanic population remained the highest (9.9 per 100,000
U.S. standard population), followed by the non-Hispanic white population (9.6).
For the non-Hispanic black population, the alcohol-induced death rate decreased
33% from 1999 to 2015, while the rate increased by 50% during the same period for
the non-Hispanic white population. Overall, from 1999 to 2015, mortality from
alcohol-induced causes increased 28% (7.1 to 9.1).
PMID- 28493857
TI - Current and Binge Drinking Among High School Students - United States, 1991-2015.
AB - Excessive drinking accounted for approximately 4,300 deaths each year among
persons aged <21 years during 2006-2010,* and underage drinking cost the United
States $24.3 billion in 2010 (1). CDC analyzed data from the national Youth Risk
Behavior Survey (YRBS) for the years 1991-2015 to examine trends in drinking by
U.S. high school students, and from the 2015 YRBS to assess the usual source of
alcohol consumed? and binge drinking intensity (i.e., the average number of
drinks consumed per binge drinking occasion).S During 1991-2007, the prevalence
of current drinking among high school students declined significantly, from
50.8% (1991) to 44.7% (2007), and then significantly declined to 32.8% in 2015.
The prevalence of binge drinking** increased from 31.3% in 1991 to 31.5% in 1999,
and then significantly declined to 17.7% in 2015. Most high school students who
drank were binge drinkers (57.8%), and 43.8% of binge drinkers consumed eight or
more drinks in a row. Despite progress, current drinking and binge drinking are
common among high school students, and many students who binge drink do so at
high intensity (i.e., eight or more drinks in a row). Widespread use of evidence
based strategies for preventing excessive drinking (e.g., increasing alcohol
taxes, regulating alcohol outlet density, and having commercial host liability
laws) could help reduce underage drinking and related harms.??.
PMID- 28493859
TI - Recommendations of the Advisory Committee on Immunization Practices for Use of
Cholera Vaccine.
AB - Cholera, caused by infection with toxigenic Vibrio cholerae bacteria of serogroup
O1 (>99% of global cases) or O139, is characterized by watery diarrhea that can
be severe and rapidly fatal without prompt rehydration. Cholera is endemic in
approximately 60 countries and causes epidemics as well. Globally, cholera
results in an estimated 2.9 million cases of disease and 95,000 deaths annually
(1). Cholera is rare in the United States, and most U.S. cases occur among
travelers to countries where cholera is endemic or epidemic. Forty-two U.S. cases
were reported in 2011 after a cholera epidemic began in Haiti (2); however, <25
cases per year have been reported in the United States since 2012.
PMID- 28493860
TI - Hepatitis C Virus Infection Among Women Giving Birth - Tennessee and United
States, 2009-2014.
AB - Hepatitis C virus (HCV) affects an estimated 3.5 million persons in the United
States (1), making it the most common bloodborne infection in the country. Recent
surveillance data showed increased rates of HCV infection among adolescents and
adults who are predominantly white, live in nonurban areas, and have a history of
injection drug use.* U.S. birth certificate data were used to analyze trends and
geographic variations in rates of HCV infection among women giving birth during
2009-2014. Birth certificates from Tennessee were used to examine individual
characteristics and outcomes associated with HCV infection, using a multivariable
model to calculate adjusted odds of HCV-related diagnosis in pregnancy among
women with live births. During 2009-2014, HCV infection present at the time of
delivery among pregnant women from states reporting HCV on the birth certificate
increased 89%, from 1.8 to 3.4 per 1,000 live births. The highest infection rate
in 2014 (22.6 per 1,000 live births) was in West Virginia; the rate in Tennessee
was 10.1. In adjusted analyses of Tennessee births, the odds of HCV infection
were approximately threefold higher among women residing in rural counties than
among those in large urban counties, 4.5-fold higher among women who smoked
cigarettes during pregnancy, and nearly 17-fold higher among women with
concurrent hepatitis B virus (HBV) infection. HCV infection among pregnant women
is an increasing and potentially modifiable threat to maternal and child health.
Clinicians and public health officials should consider individual and population
level opportunities for prevention and risk mitigation.
PMID- 28493861
TI - Maternal pre-pregnancy obesity and neuropsychological development in pre-school
children: a prospective cohort study.
AB - BackgroundMaternal pre-pregnancy obesity may impair infant neuropsychological
development, but it is unclear whether intrauterine or confounding factors drive
this association.MethodsWe assessed whether maternal pre-pregnancy obesity was
associated with neuropsychological development in 1,827 Spanish children. At 5
years, cognitive and psychomotor development was assessed using McCarthy Scales
of Children's Abilities, attention deficit hyperactivity disorder (ADHD) symptoms
using the Criteria of Diagnostic and Statistical Manual of Mental Disorders, and
autism spectrum disorder symptoms using the Childhood Asperger Syndrome Test.
Models were adjusted for sociodemographic factors and maternal intelligence
quotient. We used paternal obesity as negative control exposure as it involves
the same source of confounding than maternal obesity.ResultsThe percentage of
obese mothers and fathers was 8% and 12%, respectively. In unadjusted models,
children of obese mothers had lower scores than children of normal weight mothers
in all McCarthy subscales. After adjustment, only the verbal subscale remained
statistically significantly reduced (beta: -2.8; 95% confidence interval: -5.3,
0.2). No associations were observed among obese fathers. Maternal and paternal
obesity were associated with an increase in ADHD-related symptoms. Parental
obesity was not associated with autism symptoms.ConclusionMaternal pre-pregnancy
obesity was associated with a reduction in offspring verbal scores at pre-school
age.
PMID- 28493862
TI - FIMTrack: An open source tracking and locomotion analysis software for small
animals.
AB - Imaging and analyzing the locomotion behavior of small animals such as Drosophila
larvae or C. elegans worms has become an integral subject of biological research.
In the past we have introduced FIM, a novel imaging system feasible to extract
high contrast images. This system in combination with the associated tracking
software FIMTrack is already used by many groups all over the world. However, so
far there has not been an in-depth discussion of the technical aspects. Here we
elaborate on the implementation details of FIMTrack and give an in-depth
explanation of the used algorithms. Among others, the software offers several
tracking strategies to cover a wide range of different model organisms,
locomotion types, and camera properties. Furthermore, the software facilitates
stimuli-based analysis in combination with built-in manual tracking and
correction functionalities. All features are integrated in an easy-to-use
graphical user interface. To demonstrate the potential of FIMTrack we provide an
evaluation of its accuracy using manually labeled data. The source code is
available under the GNU GPLv3 at https://github.com/i-git/FIMTrack and pre
compiled binaries for Windows and Mac are available at http://fim.uni
muenster.de.
PMID- 28493863
TI - Visceral leishmaniasis complicating idiopathic CD4+ T-cell lymphocytopenia: 2
case reports.
PMID- 28493864
TI - Power provides protection: Genetic robustness in yeast depends on the capacity to
generate energy.
AB - The functional basis of genetic robustness, the ability of organisms to suppress
the effects of mutations, remains incompletely understood. We exposed a set of 15
strains of Saccharomyces cerevisiae form diverse environments to increasing doses
of the chemical mutagen EMS. The number of the resulting random mutations was
similar for all tested strains. However, there were differences in immediate
mortality after the mutagenic treatment and in defective growth of survivors. An
analysis of gene expression revealed that immediate mortality was lowest in
strains with lowest expression of transmembrane proteins, which are rich in thiol
groups and thus vulnerable to EMS. A signal of genuine genetic robustness was
detected for the other trait, the ability to grow well despite bearing non-lethal
mutations. Increased tolerance of such mutations correlated with high expression
of genes responsible for the oxidative energy metabolism, suggesting that the
negative effect of mutations can be buffered if enough energy is available. We
confirmed this finding in three additional tests of the ability to grow on (i)
fermentable or non-fermentable sources of carbon, (ii) under chemical inhibition
of the electron transport chain and (iii) during overexpression of its key
component, cytochrome c. Our results add the capacity to generate energy as a
general mechanism of genetic robustness.
PMID- 28493865
TI - Preheating of urine improves the specificity of urinary cryptococcal antigen
testing using the lateral flow assay.
PMID- 28493866
TI - Initial assessment of the infant with neonatal cholestasis-Is this biliary
atresia?
AB - INTRODUCTION: Optimizing outcome in biliary atresia (BA) requires timely
diagnosis. Cholestasis is a presenting feature of BA, as well as other diagnoses
(Non-BA). Identification of clinical features of neonatal cholestasis that would
expedite decisions to pursue subsequent invasive testing to correctly diagnose or
exclude BA would enhance outcomes. The analytical goal was to develop a
predictive model for BA using data available at initial presentation. METHODS:
Infants at presentation with neonatal cholestasis (direct/conjugated bilirubin >2
mg/dl [34.2 MUM]) were enrolled prior to surgical exploration in a prospective
observational multi-centered study (PROBE-NCT00061828). Clinical features
(physical findings, laboratory results, gallbladder sonography) at enrollment
were analyzed. Initially, 19 features were selected as candidate predictors. Two
approaches were used to build models for diagnosis prediction: a hierarchical
classification and regression decision tree (CART) and a logistic regression
model using a stepwise selection strategy. RESULTS: In PROBE April 2004-February
2014, 401 infants met criteria for BA and 259 for Non-BA. Univariate analysis
identified 13 features that were significantly different between BA and Non-BA.
Using a CART predictive model of BA versus Non-BA (significant factors: gamma
glutamyl transpeptidase, acholic stools, weight), the receiver operating
characteristic area under the curve (ROC AUC) was 0.83. Twelve percent of BA
infants were misclassified as Non-BA; 17% of Non-BA infants were misclassified as
BA. Stepwise logistic regression identified seven factors in a predictive model
(ROC AUC 0.89). Using this model, a predicted probability of >0.8 (n = 357)
yielded an 81% true positive rate for BA; <0.2 (n = 120) yielded an 11% false
negative rate. CONCLUSION: Despite the relatively good accuracy of our optimized
prediction models, the high precision required for differentiating BA from Non-BA
was not achieved. Accurate identification of BA in infants with neonatal
cholestasis requires further evaluation, and BA should not be excluded based only
on presenting clinical features.
PMID- 28493867
TI - Transplantation of purified iPSC-derived cardiomyocytes in myocardial infarction.
AB - BACKGROUND: Induced pluripotent stem cells (iPSC) can be differentiated into
cardiomyocytes and represent a possible autologous cell source for myocardial
repair. We analyzed the engraftment and functional effects of murine iPSC-derived
cardiomyocytes (iPSC-CMs) in a murine model of myocardial infarction. METHODS AND
RESULTS: To maximize cardiomyocyte yield and purity a genetic purification
protocol was applied. Murine iPSCs were genetically modified to express a
ZeocinTM resistance gene under control of the cardiac-specific alpha-myosin heavy
chain (alpha-MHC, MYH6) promoter. Thus, CM selection was performed during in
vitro differentiation. iPSC-CM aggregates ("cardiac bodies", CBs) were
transplanted on day 14 after LAD ligation into the hearts of previously LAD
ligated mice (800 CBs/animal; 2-3x106 CMs). Animals were treated with placebo
(PBS, n = 14) or iPSC-CMs (n = 35). Myocardial remodeling and function were
evaluated by magnetic resonance imaging (MRI), conductance catheter (CC) analysis
and histological morphometry. In vitro and in vivo differentiation was
investigated. Follow up was 28 days (including histological assessment and
functional analysis). iPSC-CM purity was >99%. Transplanted iPSC-CMs formed
mature grafts within the myocardium, expressed cardiac markers and exhibited
sarcomeric structures. Intramyocardial transplantation of iPSC-CMs significantly
improved myocardial remodeling and left ventricular function 28 days after LAD
ligation. CONCLUSIONS: We conclude that iPSCs can effectively be differentiated
into cardiomyocytes and genetically enriched to high purity. iPSC derived
cardiomyocytes engraft within the myocardium of LAD-ligated mice and contribute
to improve left ventricular function.
PMID- 28493868
TI - Vertical ground reaction force marker for Parkinson's disease.
AB - Parkinson's disease (PD) patients regularly exhibit abnormal gait patterns.
Automated differentiation of abnormal gait from normal gait can serve as a
potential tool for early diagnosis as well as monitoring the effect of PD
treatment. The aim of current study is to differentiate PD patients from healthy
controls, on the basis of features derived from plantar vertical ground reaction
force (VGRF) data during walking at normal pace. The current work presents a
comprehensive study highlighting the efficacy of different machine learning
classifiers towards devising an accurate prediction system. Selection of
meaningful feature based on sequential forward feature selection, the swing time,
stride time variability, and center of pressure features facilitated successful
classification of control and PD gaits. Support Vector Machine (SVM), K-nearest
neighbor (KNN), random forest, and decision trees classifiers were used to build
the prediction model. We found that SVM with cubic kernel outperformed other
classifiers with an accuracy of 93.6%, the sensitivity of 93.1%, and specificity
of 94.1%. In comparison to other studies, utilizing same dataset, our designed
prediction system improved the classification performance by approximately 10%.
The results of the current study underscore the ability of the VGRF data obtained
non-invasively from wearable devices, in combination with a SVM classifier
trained on meticulously selected features, as a tool for diagnosis of PD and
monitoring effectiveness of therapy post pathology.
PMID- 28493869
TI - Identification of the potentiating mutations and synergistic epistasis that
enabled the evolution of inter-species cooperation.
AB - Microbes often engage in cooperation through releasing biosynthetic compounds
required by other species to grow. Given that production of costly biosynthetic
metabolites is generally subjected to multiple layers of negative feedback,
single mutations may frequently be insufficient to generate cooperative
phenotypes. Synergistic epistatic interactions between multiple coordinated
changes may thus often underlie the evolution of cooperation through
overproduction of metabolites. To test the importance of synergistic mutations in
cooperation we used an engineered bacterial consortium of an Escherichia coli
methionine auxotroph and Salmonella enterica. S. enterica relies on carbon by
products from E. coli if lactose is the only carbon source. Directly selecting
wild-type S. enterica in an environment that favored cooperation through
secretion of methionine only once led to a methionine producer, and this producer
both took a long time to emerge and was not very effective at cooperating. On the
other hand, when an initial selection for resistance of S. enterica to a toxic
methionine analog, ethionine, was used, subsequent selection for cooperation with
E. coli was rapid, and the resulting double mutants were much more effective at
cooperation. We found that potentiating mutations in metJ increase expression of
metA, which encodes the first step of methionine biosynthesis. This increase in
expression is required for the previously identified actualizing mutations in
metA to generate cooperation. This work highlights that where biosynthesis of
metabolites involves multiple layers of regulation, significant secretion of
those metabolites may require multiple mutations, thereby constraining the
evolution of cooperation.
PMID- 28493871
TI - Ileus in children presenting with diarrhea and severe acute malnutrition: A chart
review.
AB - BACKGROUND: Severely malnourished children aged under five years requiring
hospital admission for diarrheal illness frequently develop ileus during
hospitalization with often fatal outcomes. However, there is no data on risk
factors and outcome of ileus in such children. We intended to evaluate predictive
factors for ileus during hospitalization and their outcomes.
METHODOLOGY/PRINCIPAL FINDINGS: This was a retrospective chart review that
enrolled severely malnourished children under five years old with diarrhea,
admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease
Research, Bangladesh between April 2011 and August 2012. We used electronic
database to have our chart abstraction from previously admitted children in the
hospital. The clinical and laboratory characteristics of children with (cases =
45), and without ileus (controls = 261) were compared. Cases were first
identified by observation of abnormal bowel sounds on physical examination and
confirmed with abdominal radiographs. For this comparison, Chi-square test was
used to measure the difference in proportion, Student's t-test to calculate the
difference in mean for normally distributed data and Mann-Whitney test for data
that were not normally distributed. Finally, in identifying independent risk
factors for ileus, logistical regression analysis was performed. Ileus was
defined if a child developed abdominal distension and had hyperactive or sluggish
or absent bowel sound and a radiologic evidence of abdominal gas-fluid level
during hospitalization. Logistic regression analysis adjusting for potential
confounders revealed that the independent risk factors for admission for ileus
were reluctance to feed (odds ratio [OR] = 3.22, 95% confidence interval [CI] =
1.24-8.39, p = 0.02), septic shock (OR = 3.62, 95% CI = 1.247-8.95, p<0.01), and
hypokalemia (OR = 1.99, 95% CI = 1.03-3.86, p = 0.04). Mortality was
significantly higher in cases compared to controls (22% vs. 8%, p<0.01) in
univariate analysis; however, in multivariable regression analysis, after
adjusting for potential confounders such as septic shock, no association was
found between ileus and death (OR = 2.05, 95% CI = 0.68-6.14, p = 0.20). In a
separate regression analysis model, after adjusting for potential confounders
such as ileus, reluctance to feed, hypokalemia, hypocalcemia, and blood
transfusion, septic shock (OR = 168.84, 95% CI = 19.27-1479.17, p<0.01) emerged
as the only independent predictor of death in severely malnourished diarrheal
children. CONCLUSIONS/SIGNIFICANCE: This study suggests that the identification
of simple independent admission risk factors for ileus and risk factors for death
in hospitalized severely malnourished diarrheal children may prompt clinicians to
be more vigilant in managing these conditions, especially in resource-limited
settings in order to decrease ileus and ileus-related fatal outcomes in such
children.
PMID- 28493872
TI - Geographic distribution of vestibular schwannomas in West Scotland between 2000
2015.
AB - BACKGROUND: Although the natural history of vestibular schwannomas (VS) has been
previously studied, few studies have investigated associated epidemiological
factors, primarily because of the lack of large available cohorts. OBJECTIVE: The
objective of this study was to perform a multi-scale geographical analysis of the
period prevalence of VS in West Scotland from 2000 to 2015. METHODS: Adults
diagnosed with sporadic VS were identified through the National Health Services
of West Scotland database and geocoded to the unit postcode. To assess whether
the cohort of VS cases could be pooled into a period prevalence measure, the
locations of VS cases were analyzed by sex using Cross-L and Difference-K
functions. VS period prevalence was examined at two aggregate spatial scales: the
postcode district and a coarser scale of NHS Health Boards. The spatial structure
of period prevalence within each level of spatial aggregation was measured using
univariate global and local Moran's I. Bivariate local Moran's I was used to
examine the between-scale variability in period prevalence from the postcode
district level to the NHS Health Boards levels. Prior to spatial autocorrelation
analyses, the period prevalence at the postcode district was tested for
stratified spatial heterogeneity within the NHS Health Boards using Wang's q
Statistic. RESULTS: A total of 512 sporadic VS were identified in a population of
over 3.1 million. Between 2000 and 2015, VS period prevalence was highest within
the NHS Health Boards of Greater Glasgow and Clyde, Ayrshire and Arran and the
Western Isles. However, at the NHS scale, period prevalence exhibited no spatial
autocorrelation globally or locally. At the district scale, Highland exhibited
the most unusual local spatial autocorrelation. Bivariate local Moran's I results
indicated general stability of period prevalence across the postcode district to
Health Boards scales. However, locally, some postcode districts in Greater
Glasgow and Clyde, Ayrshire and Arran exhibited unusually low district to zone
spatial autocorrelation in period prevalence, as did the southern parts of the
Western Isles. Some unusually high period prevalence values between the postcode
district to Health Board scale were found in Tayside, Forth Valley and Dumfries
and Galloway. CONCLUSION: Geographic variability in VS in West Scotland was
identified in this patient population, showing that there are areas, even remote,
with unusually high or low period prevalence. This can be partially attributed to
links between primary and tertiary care. Potential genetic or environmental risk
factors that may contribute to geographic variation in this disease within
Scotland are also a possibility but require further investigation.
PMID- 28493870
TI - Functional male accessory glands and fertility in Drosophila require novel
ecdysone receptor.
AB - In many insects, the accessory gland, a secretory tissue of the male reproductive
system, is essential for male fertility. Male accessory gland is the major source
of proteinaceous secretions, collectively called as seminal proteins (or
accessory gland proteins), which upon transfer, manipulate the physiology and
behavior of mated females. Insect hormones such as ecdysteroids and juvenoids
play a key role in accessory gland development and protein synthesis but little
is known about underlying molecular players and their mechanism of action.
Therefore, in the present study, we examined the roles of hormone-dependent
transcription factors (Nuclear Receptors), in accessory gland development,
function and male fertility of a genetically tractable insect model, Drosophila
melanogaster. First, we carried out an RNAi screen involving 19 hormone
receptors, individually and specifically, in a male reproductive tissue
(accessory gland) for their requirement in Drosophila male fertility.
Subsequently, by using independent RNAi/ dominant negative forms, we show that
Ecdysone Receptor (EcR) is essential for male fertility due to its requirement in
the normal development of accessory glands in Drosophila: EcR depleted glands
fail to make seminal proteins and have dying cells. Further, our data point to a
novel ecdysone receptor that does not include Ultraspiracle but is probably
comprised of EcR isoforms in Drosophila male accessory glands. Our data suggest
that this novel ecdysone receptor might act downstream of homeodomain
transcription factor paired (prd) in the male accessory gland. Overall, the study
suggests novel ecdysone receptor as an important player in the hormonal
regulation of seminal protein production and insect male fertility.
PMID- 28493873
TI - Modeling of a negative feedback mechanism explains antagonistic pleiotropy in
reproduction in domesticated Caenorhabditis elegans strains.
AB - Most biological traits and common diseases have a strong but complex genetic
basis, controlled by large numbers of genetic variants with small contributions
to a trait or disease risk. The effect-size of most genetic variants is not
absolute and is instead dependent upon multiple factors such as the age and
genetic background of an organism. In order to understand the mechanistic basis
of these changes, we characterized heritable trait differences between two
domesticated strains of C. elegans. We previously identified a major effect
locus, caused in part by a mutation in a component of the NURF chromatin
remodeling complex, that regulates reproductive output in an age-dependent
manner. The effect-size of this locus changes from positive to negative over the
course of an animal's reproductive lifespan. Here, we use a previously published
macroscale model of the egg-laying rate in C. elegans to show that time-dependent
effect-size is explained by an unequal use of sperm combined with negative
feedback between sperm and ovulation rate. We validate key predictions of this
model with controlled mating experiments and quantification of oogenesis and
sperm use. Incorporation of this model into QTL mapping allows us to identify and
partition new QTLs into specific aspects of the egg-laying process. Finally, we
show how epistasis between two genetic variants is predicted by this modeling as
a consequence of the unequal use of sperm. This work demonstrates how modeling of
multicellular communication systems can improve our ability to predict and
understand the role of genetic variation on a complex phenotype. Negative
autoregulatory feedback loops, common in transcriptional regulation, could play
an important role in modifying genetic architecture in other traits.
PMID- 28493874
TI - SrCrxFe12-xO19 nanoceramics as an effective catalyst for desulfurization of
liquid fuels: Green sol-gel synthesis, characterization, magnetic and optical
properties.
AB - In this work, SrCrxFe12-xO19 (x = 0.0, 0.5, 1.0, 1.5) nanostructures were
successfully synthesized by sol-gel auto-combustion method, and different
aminoacids were used as green reductants. Various analysis results show that
SrCrxFe12-xO19 nanoparticles synthesized successfully.The present study shows
that SrCrxFe12-xO19 nanoparticle could be used as adsorbent for the
desulfurization of liquid fuels. Increasing of nanoparticles concentration was
caused to increase the adsorption rate of sulfur contents of fuel. The adsorption
rate of sulfur contents of fuel in various concentrations 4.5, 9.5, and 18.5 g. L
-1 of SrCrxFe12-xO19 nanoparticles in solution was estimated about 39, 50, and
62% for 30 min, respectively. The results of catalytic tests reveals that
SrCrxFe12-xO19 nanoparticles have the potential to be used as a new kind of
semiconductor catalysts for the desulfurization of liquid fuels. Magnetic
property of the final sample was measured at room temperature by a vibration
sample magnetometer (VSM) and shown that the intrinsic coercivity of product is
about 6000 Oe and it exhibits characteristics of single magnetic domains (Mr/ Ms
= 0.53).
PMID- 28493875
TI - Effect of a high-fat diet and alcohol on cutaneous repair: A systematic review of
murine experimental models.
AB - BACKGROUND AND PURPOSE: Chronic alcohol intake associated with an inappropriate
diet can cause lesions in multiple organs and tissues and complicate the tissue
repair process. In a systematic review, we analyzed the relevance of alcohol and
high fat consumption to cutaneous and repair, compared the main methodologies
used and the most important parameters tested. Preclinical investigations with
murine models were assessed to analyze whether the current evidence support
clinical trials. METHODS: The studies were selected from MEDLINE/PubMed and
Scopus databases, according to Fig 1. All 15 identified articles had their data
extracted. The reporting bias was investigated according to the ARRIVE (Animal
Research: Reporting of in Vivo Experiments) strategy. RESULTS: In general,
animals offered a high-fat diet and alcohol showed decreased cutaneous wound
closure, delayed skin contraction, chronic inflammation and incomplete re
epithelialization. CONCLUSION: In further studies, standardized experimental
design is needed to establish comparable study groups and advance the overall
knowledge background, facilitating data translatability from animal models to
human clinical conditions.
PMID- 28493876
TI - The effect of sphingosine-1-phosphate on colonic smooth muscle contractility:
Modulation by TNBS-induced colitis.
AB - AIM: Increased levels of circulating sphingosine-1-phosphate (S1P) have been
reported in ulcerative colitis. The objective of this study was to examine the
effect of S1P on colonic smooth muscle contractility and how is it affected by
colitis. METHODS: Colonic inflammation was induced by intrarectal administration
of trinitrobenzene sulfonic acid. Five days later colon segments were isolated
and used for contractility experiments and immunoblotting. RESULTS: S1P
contracted control and inflamed colon segments and the contraction was
significantly greater in inflamed colon segments. S1P-induced contraction was
mediated by S1PR1 and S1PR2 in control and S1PR2 in inflamed colon segments.
S1PR3 did not play a significant role in S1P-induced contractions in control or
inflamed colon. S1PR1, S1PR2 and S1PR3 proteins were expressed in colon segments
from both groups. The expression of S1PR1 and S1PR2 was significantly enhanced in
control and inflamed colon segments, respectively. S1PR3 levels however were not
significantly different between the two groups. Nifedipine significantly reduced
S1P-induced contraction in control but not inflamed colon segments. Thapsigargin
significantly reduced S1P-induced contraction of the inflamed colon. GF 109203X
and Y-27632, alone abolished S1P-induced contraction of the control but not
inflamed colon segments. Combination of GF 109203X, Y-27632 and thapsigargin
abolished S1P-induced contraction of inflamed colon segments. CONCLUSION: S1P
contracted control colon via S1PR1 and S1PR2 and inflamed colon exclusively via
S1PR2. Calcium influx (control) or release (inflamed) and calcium sensitization
are involved in S1P-induced contraction. Exacerbated response to S1P in colitic
colon segments may explain altered colonic motility reported in patients and
experimental models of inflammatory bowel disease.
PMID- 28493877
TI - CO2 driven endotracheal tube cuff control in critically ill patients: A
randomized controlled study.
AB - BACKGROUND: To determine the safety and clinical efficacy of an innovative
integrated airway system (AnapnoGuardTM 100 system) that continuously monitors
and controls the cuff pressure (Pcuff), while facilitating the aspiration of
subglottic secretions (SS). METHODS: This was a prospective, single centre, open
label, randomized, controlled feasibility and safety trial. The primary endpoint
of the study was the rate of device related adverse events (AE) and serious AE
(SAE) as a result of using AnapnoGuard (AG) 100 during mechanical ventilation.
Secondary endpoints were: (1) mechanical complications rate (2) ICU staff
satisfaction; (3) VAP occurrence; (4) length of mechanical ventilation; (5)
length of Intensive Care Unit stay and mortality; (6) volume of evacuated
subglottic secretions. Sixty patients were randomized to be intubated with the AG
endotracheal-tube (ETT) and connected to the AG 100 system allowing Pcuff
adjustment and SS aspiration; or with an ETT combined with SS drainage and Pcuff
controlled manually. RESULTS: No difference in adverse events rate was identified
between the groups. The use of AG system was associated with a significantly
higher incidence of Pcuff determinations in the safety range (97.3% vs. 71%;
p<0.01) and a trend to a greater volume of aspirated SS secretions: (192.0[64
413] ml vs. 150[50-200], p = 0.19 (total)); (57.8[20-88.7] ml vs. 50[18.7-62] ml,
p = 0.11 (daily)). No inter-group difference was detected using AG system vs.
controls in terms of post-extubation throat pain level (0 [0-2] vs. 0 [0-3]; p =
0.7), hoarseness (42.9% vs. 75%; p = 0.55) and tracheal mucosa oedema (16.7% vs.
10%; p = 0.65). Patients enrolled in the AG group had a trend to reduced VAP risk
of ventilator-associated pneumonia(VAP) (14.8% vs. 40%; p = 0.06), which were
more frequently monomicrobial (25% vs. 70%; p = 0.03). No statistically
significant difference was observed in duration of mechanical ventilation, ICU
stay, and mortality. CONCLUSIONS: The use AG 100 system and AG tube in critically
ill intubated patients is safe and effective in Pcuff control and SS drainage.
Its protective role against VAP needs to be confirmed in a larger randomized
trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT01550978. Date of registration:
February 21, 2012.
PMID- 28493878
TI - 5alpha-reductase 1 mRNA levels are positively correlated with TRAMP mouse
prostate most severe lesion scores.
AB - BACKGROUND: The contribution of 5alpha-reductase 1 and 5alpha-reductase 2 to
prostate cancer development and progression is not clearly understood. TRAMP mice
are a common prostate cancer model, in which 5alpha-reductase 1 and 5alpha
reductase 2 expression levels, along with prostate lesions scores, have not been
investigated at different time points to further understand prostate
carcinogenesis. METHOD/PRINCIPAL FINDINGS: To this end, 8-, 12-, 16-, and 20-week
old male C57BL/6TRAMP x FVB mice prostate most severe and most common lesion
scores, 5alpha-reductase 1 and 5alpha-reductase 2 in situ hybridization
expression, and Ki-67, androgen receptor, and apoptosis immunohistochemistry
levels were measured. Levels of these markers were quantified in prostate
epithelium, hyperplasia, and tumors sections. Mice developed low- to high-grade
prostatic intraepithelial neoplasia at 8 weeks as the most severe and most common
lesions, and moderate- and high-grade prostatic intraepithelial neoplasia at 12
and 16 weeks as the most severe lesion in all lobes. Moderately differentiated
adenocarcinoma was observed at 20 weeks in all lobes. Poorly differentiated
carcinoma was not observed in any lobe until 12-weeks-old. 5alpha-reductase 1 and
5alpha-reductase 2 were not significantly decreased in tumors compared to
prostate epithelium and hyperplasia in all groups, while proliferation,
apoptosis, and androgen receptor were either notably or significantly decreased
in tumors compared with prostate epithelium and hyperplasia in most or all
groups. Prostate 5alphaR1 levels were positively correlated with adjusted
prostate most severe lesion scores. CONCLUSION: Downregulation of androgen
receptor and 5alpha-reductase 2, along with upregulation of 5alpha-reductase 1 in
tumors may promote prostatic intraepithelial neoplasia and prostate cancer
development in TRAMP mice.
PMID- 28493879
TI - Heterogeneous Ag-TiO2-SiO2 composite materials as novel catalytic systems for
selective epoxidation of cyclohexene by H2O2.
AB - TiO2-SiO2 composites were synthesized using cetyl trimethyl ammonium bromide
(CTAB) as the structure directing template. Self-assembly hexadecyltrimethyl-
ammonium bromide TiO2-SiO2/(CTAB) were soaked into silver nitrate (AgNO3) aqueous
solution. The Ag-TiO2-SiO2(Ag-TS) composite were prepared via a precipitation of
AgBr in soaking process and its decomposition at calcination stage. Structural
characterization of the materials was carried out by various techniques including
X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission
electron microscopy (TEM), N2 adsorption-desorption and ultraviolet visible
spectroscopy (UV-Vis). Characterization results revealed that Ag particles were
incorporated into hierarchical TiO2-SiO2 without significantly affecting the
structures of the supports. Further heating-treatment at 723 K was more favorable
for enhancing the stability of the Ag-TS composite. The cyclohexene oxide was the
major product in the epoxidation using H2O2 as the oxidant over the Ag-TS
catalysts. Besides, the optimum catalytic activity and stability of Ag-TS
catalysts were obtained under operational conditions of calcined at 723 K for 2
h, reaction time of 120 min, reaction temperature of 353 K, catalyst amount of 80
mg, aqueous H2O2 (30 wt.%) as oxidant and chloroform as solvent. High catalytic
activity with conversion rate up to 99.2% of cyclohexene oxide could be
obtainable in water-bathing. The catalyst was found to be stable and could be
reused three times without significant loss of catalytic activity under the
optimized reaction conditions.
PMID- 28493880
TI - Identifying stochastic oscillations in single-cell live imaging time series using
Gaussian processes.
AB - Multiple biological processes are driven by oscillatory gene expression at
different time scales. Pulsatile dynamics are thought to be widespread, and
single-cell live imaging of gene expression has lead to a surge of dynamic,
possibly oscillatory, data for different gene networks. However, the regulation
of gene expression at the level of an individual cell involves reactions between
finite numbers of molecules, and this can result in inherent randomness in
expression dynamics, which blurs the boundaries between aperiodic fluctuations
and noisy oscillators. This underlies a new challenge to the experimentalist
because neither intuition nor pre-existing methods work well for identifying
oscillatory activity in noisy biological time series. Thus, there is an acute
need for an objective statistical method for classifying whether an
experimentally derived noisy time series is periodic. Here, we present a new data
analysis method that combines mechanistic stochastic modelling with the powerful
methods of non-parametric regression with Gaussian processes. Our method can
distinguish oscillatory gene expression from random fluctuations of non
oscillatory expression in single-cell time series, despite peak-to-peak
variability in period and amplitude of single-cell oscillations. We show that our
method outperforms the Lomb-Scargle periodogram in successfully classifying cells
as oscillatory or non-oscillatory in data simulated from a simple genetic
oscillator model and in experimental data. Analysis of bioluminescent live-cell
imaging shows a significantly greater number of oscillatory cells when luciferase
is driven by a Hes1 promoter (10/19), which has previously been reported to
oscillate, than the constitutive MoMuLV 5' LTR (MMLV) promoter (0/25). The method
can be applied to data from any gene network to both quantify the proportion of
oscillating cells within a population and to measure the period and quality of
oscillations. It is publicly available as a MATLAB package.
PMID- 28493881
TI - shinyheatmap: Ultra fast low memory heatmap web interface for big data genomics.
AB - BACKGROUND: Transcriptomics, metabolomics, metagenomics, and other various next
generation sequencing (-omics) fields are known for their production of large
datasets, especially across single-cell sequencing studies. Visualizing such big
data has posed technical challenges in biology, both in terms of available
computational resources as well as programming acumen. Since heatmaps are used to
depict high-dimensional numerical data as a colored grid of cells, efficiency and
speed have often proven to be critical considerations in the process of
successfully converting data into graphics. For example, rendering interactive
heatmaps from large input datasets (e.g., 100k+ rows) has been computationally
infeasible on both desktop computers and web browsers. In addition to memory
requirements, programming skills and knowledge have frequently been barriers-to
entry for creating highly customizable heatmaps. RESULTS: We propose
shinyheatmap: an advanced user-friendly heatmap software suite capable of
efficiently creating highly customizable static and interactive biological
heatmaps in a web browser. shinyheatmap is a low memory footprint program, making
it particularly well-suited for the interactive visualization of extremely large
datasets that cannot typically be computed in-memory due to size restrictions.
Also, shinyheatmap features a built-in high performance web plug-in, fastheatmap,
for rapidly plotting interactive heatmaps of datasets as large as 105-107 rows
within seconds, effectively shattering previous performance benchmarks of heatmap
rendering speed. CONCLUSIONS: shinyheatmap is hosted online as a freely available
web server with an intuitive graphical user interface: http://shinyheatmap.com.
The methods are implemented in R, and are available as part of the shinyheatmap
project at: https://github.com/Bohdan-Khomtchouk/shinyheatmap. Users can access
fastheatmap directly from within the shinyheatmap web interface, and all source
code has been made publicly available on Github: https://github.com/Bohdan
Khomtchouk/fastheatmap.
PMID- 28493882
TI - Selective pre-priming of HA-specific CD4 T cells restores immunological
reactivity to HA on heterosubtypic influenza infection.
AB - A hallmark of the immune response to influenza is repeated encounters with
proteins containing both genetically conserved and variable components.
Therefore, the B and T cell repertoire is continually being remodeled, with
competition between memory and naive lymphocytes. Our previous work using a mouse
model of secondary heterosubtypic influenza infection has shown that this
competition results in a focusing of CD4 T cell response specificity towards
internal virion proteins with a selective decrease in CD4 T cell reactivity to
the novel HA epitopes. Strikingly, this shift in CD4 T cell specificity was
associated with a diminished anti-HA antibody response. Here, we sought to
determine whether the loss in HA-specific reactivity that occurs as a consequence
of immunological memory could be reversed by selectively priming HA-specific CD4
T cells prior to secondary infection. Using a peptide-based priming strategy, we
found that selective expansion of the anti-HA CD4 T cell memory repertoire
enhanced HA-specific antibody production upon heterosubtypic infection. These
results suggest that the potentially deleterious consequences of repeated
exposure to conserved influenza internal virion proteins could be reversed by
vaccination strategies that selectively arm the HA-specific CD4 T cell
compartment. This could be a potentially useful pre-pandemic vaccination strategy
to promote accelerated neutralizing antibody production on challenge with a
pandemic influenza strain that contains few conserved HA epitopes.
PMID- 28493883
TI - Lithocholic acid controls adaptive immune responses by inhibition of Th1
activation through the Vitamin D receptor.
AB - Bile acids are established signaling molecules next to their role in the
intestinal emulsification and uptake of lipids. We here aimed to identify a
potential interaction between bile acids and CD4+ Th cells, which are central in
adaptive immune responses. We screened distinct bile acid species for their
potency to affect T cell function. Primary human and mouse CD4+ Th cells as well
as Jurkat T cells were used to gain insight into the mechanism underlying these
effects. We found that unconjugated lithocholic acid (LCA) impedes Th1 activation
as measured by i) decreased production of the Th1 cytokines IFNgamma and
TNFalphaalpha, ii) decreased expression of the Th1 genes T-box protein expressed
in T cells (T-bet), Stat-1 and Stat4, and iii) decreased STAT1alpha/beta
phosphorylation. Importantly, we observed that LCA impairs Th1 activation at
physiological relevant concentrations. Profiling of MAPK signaling pathways in
Jurkat T cells uncovered an inhibition of ERK-1/2 phosphorylation upon LCA
exposure, which could provide an explanation for the impaired Th1 activation. LCA
induces these effects via Vitamin D receptor (VDR) signaling since VDR RNA
silencing abrogated these effects. These data reveal for the first time that LCA
controls adaptive immunity via inhibition of Th1 activation. Many factors
influence LCA levels, including bile acid-based drugs and gut microbiota. Our
data may suggest that these factors also impact on adaptive immunity via a yet
unrecognized LCA-Th cell axis.
PMID- 28493884
TI - Non-linear growth in tree ferns, Dicksonia antarctica and Cyathea australis.
AB - Tree ferns are an important structural component of forests in many countries.
However, because their regeneration is often unrelated to major disturbances,
their age is often difficult to determine. In addition, rates of growth may not
be uniform, which further complicates attempts to determine their age. In this
study, we measured 5 years of growth of Cyathea australis and Dicksonia
antarctica after a large wildfire in 2009 in south-eastern Australia. We found
growth rates of these two species were unaffected by aspect and elevation but
slope had a minor effect with D. antarctica growing 0.3mm faster for each
additional degree of slope. Geographic location influenced growth in both species
by up to 12 - 14mm/yr. The most consistent factor influencing growth rate,
however, was initial height at the time of the 2009 fire; a finding consistent in
both species and all geographic locations. For both tree fern species,
individuals that were taller at the commencement of the study had greater overall
growth for the duration of the study. This effect did not decrease even among the
tallest tree ferns in our study (up to 6 metres tall). Overall, Cyathea australis
averaged 73 (+/- 22)mm/year of growth (+/- 1SD), with the rate increasing 5mm/yr
per metre of additional height. Dicksonia antarctica averaged 33 (+/- 13)mm/year,
increasing by 6mm/yr/m. Growth rates dependent on initial height were unexpected
and we discuss possible reasons for this finding. Variable growth rates also
suggest that common age estimation methods of dividing height by average growth
rate are likely to underestimate the age of short tree ferns, while
overestimating the age of tall tree ferns, particularly if they have been subject
to a fire.
PMID- 28493886
TI - Narrow microtunnel technology for the isolation and precise identification of
axonal communication among distinct hippocampal subregion networks.
AB - Communication between different sub regions of the hippocampus is fundamental to
learning and memory. However accurate knowledge about information transfer
between sub regions from access to the activity in individual axons is lacking.
MEMS devices with microtunnels connecting two sub networks have begun to approach
this problem but the commonly used 10 MUm wide tunnels frequently measure signals
from multiple axons. To reduce this complexity, we compared polydimethylsiloxane
(PDMS) microtunnel devices each with a separate tunnel width of 2.5, 5 or 10 MUm
bridging two wells aligned over a multi electrode array (MEA). Primary rat
neurons were grown in the chambers with neurons from the dentate gyrus on one
side and hippocampal CA3 on the other. After 2-3 weeks of culture, spontaneous
activity in the axons inside the tunnels was recorded. We report
electrophysiological, exploratory data analysis for feature clustering and visual
evidence to support the expectation that 2.5 MUm wide tunnels have fewer axons
per tunnel and therefore more clearly delineated signals than 10 or 5 MUm wide
tunnels. Several measures indicated that fewer axons per electrode enabled more
accurate detection of spikes. A clustering analysis comparing the variations of
spike height and width for different tunnel widths revealed tighter clusters
representing unique spikes with less height and width variation when measured in
narrow tunnels. Wider tunnels tended toward more diffuse clusters from a
continuum of spike heights and widths. Standard deviations for multiple cluster
measures, such as Average Dissimilarity, Silhouette Value (S) and Separation
Factor (average dissimilarity/S value), support a conclusion that 2.5 MUm wide
tunnels containing fewer axons enable more precise determination of individual
action potential peaks, their propagation direction, timing, and information
transfer between sub networks.
PMID- 28493885
TI - Genotypic and phenotypic diversity of Lactobacillus rhamnosus clinical isolates,
their comparison with strain GG and their recognition by complement system.
AB - Lactobacillus rhamnosus strains are ubiquitous in fermented foods, and in the
human body where they are commensals naturally present in the normal microbiota
composition of gut, vagina and skin. However, in some cases, Lactobacillus spp.
have been implicated in bacteremia. The aim of the study was to examine the
genomic and immunological properties of 16 clinical blood isolates of L.
rhamnosus and to compare them to the well-studied L. rhamnosus probiotic strain
GG. Blood cultures from bacteremic patients were collected at the Helsinki
University Hospital laboratory in 2005-2011 and L. rhamnosus strains were
isolated and characterized by genomic sequencing. The capacity of the L.
rhamnosus strains to activate serum complement was studied using immunological
assays for complement factor C3a and the terminal pathway complement complex
(TCC). Binding of complement regulators factor H and C4bp was also determined
using radioligand assays. Furthermore, the isolated strains were evaluated for
their ability to aggregate platelets and to form biofilms in vitro. Genomic
comparison between the clinical L. rhamnosus strains showed them to be clearly
different from L. rhamnosus GG and to cluster in two distinct lineages. All L.
rhamnosus strains activated complement in serum and none of them bound complement
regulators. Four out of 16 clinical blood isolates induced platelet aggregation
and/or formed more biofilms than L. rhamnosus GG, which did not display platelet
aggregation activity nor showed strong biofilm formation. These findings suggest
that clinical L. rhamnosus isolates show considerable heterogeneity but are
clearly different from L. rhamnosus GG at the genomic level. All L. rhamnosus
strains are still normally recognized by the human complement system.
PMID- 28493887
TI - Effect of lifestyle interventions on cardiovascular risk factors among adults
without impaired glucose tolerance or diabetes: A systematic review and meta
analysis.
AB - Structured lifestyle interventions can reduce diabetes incidence and
cardiovascular disease (CVD) risk among persons with impaired glucose tolerance
(IGT), but it is unclear whether they should be implemented among persons without
IGT. We conducted a systematic review and meta-analyses to assess the
effectiveness of lifestyle interventions on CVD risk among adults without IGT or
diabetes. We systematically searched MEDLINE, EMBASE, CINAHL, Web of Science, the
Cochrane Library, and PsychInfo databases, from inception to May 4, 2016. We
selected randomized controlled trials of lifestyle interventions, involving
physical activity (PA), dietary (D), or combined strategies (PA+D) with follow-up
duration >=12 months. We excluded all studies that included individuals with IGT,
confirmed by 2-hours oral glucose tolerance test (75g), but included all other
studies recruiting populations with different glycemic levels. We stratified
studies by baseline glycemic levels: (1) low-range group with mean fasting plasma
glucose (FPG) <5.5mmol/L or glycated hemoglobin (A1C) <5.5%, and (2) high-range
group with FPG >=5.5mmol/L or A1C >=5.5%, and synthesized data using random
effects models. Primary outcomes in this review included systolic blood pressure
(SBP), diastolic blood pressure (DBP), total cholesterol (TC), low density
lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C),
and triglycerides (TG). Totally 79 studies met inclusion criteria. Compared to
usual care (UC), lifestyle interventions achieved significant improvements in SBP
(-2.16mmHg[95%CI, -2.93, -1.39]), DBP (-1.83mmHg[-2.34, -1.31]), TC (-0.10mmol/L[
0.15, -0.05]), LDL-C (-0.09mmol/L[-0.13, -0.04]), HDL-C (0.03mmol/L[0.01, 0.04]),
and TG (-0.08mmol/L[-0.14, -0.03]). Similar effects were observed among both low
and high-range study groups except for TC and TG. Similar effects also appeared
in SBP and DBP categories regardless of follow-up duration. PA+D interventions
had larger improvement effects on CVD risk factors than PA alone interventions.
In adults without IGT or diabetes, lifestyle interventions resulted in
significant improvements in SBP, DBP, TC, LDL-C, HDL-C, and TG, and might further
reduce CVD risk.
PMID- 28493889
TI - Characterization of a novel antibiofilm effect of nitric oxide-releasing aspirin
(NCX-4040) on Candida albicans isolates from denture stomatitis patients.
AB - Candida albicans biofilms play a key role in denture stomatitis, one of the most
common oral pathologies in elderly people. Because biofilms are highly resistant
to antifungals, new pharmacological strategies are needed. Aspirin and nitric
oxide-donor molecules have both shown antibiofilm effects on C. albicans, making
them promising candidates for treatment. In this study, we evaluated the
antifungal/antibiofilm effect of a nitric-oxide releasing aspirin (NO-ASA) on C.
albicans isolates from denture stomatitis patients in vitro. Disk diffusion
assays showed that while NO-ASA had no antifungal effect, the drug potentiated
fluconazole inhibition zone diameters, increasing the effect of fluconazole by 20
30% (p<0.05). The effect of NO-ASA on the morphogenesis of C. albicans was
evaluated using light microscopy after inducing hyphae formation. For all
clinical strains assayed, 125 MUM NO-ASA significantly decreased the number of
filamentous cells present (p<0.01). Adhesion to abiotic surfaces, a critical
event for biofilm formation, was evaluated in 96-well polystyrene plates using
crystal violet assay; 125 MUM NO-ASA significantly inhibited adhesion. Biofilms
were observed with scanning electron microscopy (SEM) and quantified using XTT
reduction assay. NO-ASA decreased biofilm formation (IC50 ranging from 300 MUM to
700 MUM), consistent with SEM findings of altered biofilm microarchitecture. PGE2
and carboxy-PTIO (an NO scavenger) both blocked the antibiofilm effects of NO
ASA, suggesting that the efficacy of NO-ASA may be associated with both
inhibition of PGE2 synthesis and release of NO. NO-ASA is a promising novel
antibiofilm agent for treating fluconazole-resistant strains of C. albicans.
PMID- 28493888
TI - The mitochondrial SIR2 related protein 2 (SIR2RP2) impacts Leishmania donovani
growth and infectivity.
AB - BACKGROUND: Leishmania donovani, a protozoan parasite is the major causative
agent of visceral leishmaniasis. Increased toxicity and resistance to the
existing repertoire of drugs has been reported. Hence, an urgent need exists for
identifying newer drugs and drug targets. Previous reports have shown sirtuins
(Silent Information Regulator) from kinetoplastids as promising drug targets.
Leishmania species code for three SIR2 (Silent Information Regulator) related
proteins. Here, we for the first time report the functional characterization of
SIR2 related protein 2 (SIR2RP2) of L. donovani. METHODOLOGY: Recombinant L.
donovani SIR2RP2 was expressed in E. coli and purified. The enzymatic functions
of SIR2RP2 were determined. The subcellular localization of LdSIR2RP2 was done by
constructing C-terminal GFP-tagged full-length LdSIR2RP2. Deletion mutants of
LdSIR2RP2 were generated in Leishmania by double targeted gene replacement
methodology. These null mutants were tested for their proliferation, virulence,
cell cycle defects, mitochondrial functioning and sensitivity to known SIR2
inhibitors. CONCLUSION: Our data suggests that LdSIR2RP2 possesses NAD+-dependent
ADP-ribosyltransferase activity. However, NAD+-dependent deacetylase and
desuccinylase activities were not detected. The protein localises to the
mitochondrion of the promastigotes. Gene deletion studies showed that
DeltaLdSIR2RP2 null mutants had restrictive growth phenotype associated with
accumulation of cells in the G2/M phase and compromised mitochondrial
functioning. The null mutants had attenuated infectivity. Deletion of LdSIR2RP2
resulted in increased sensitivity of the parasites to the known SIR2 inhibitors.
The sirtuin inhibitors inhibited the ADP-ribosyltransferase activity of
recombinant LdSIR2RP2. In conclusion, sirtuins could be used as potential new
drug targets for visceral leishmaniasis.
PMID- 28493890
TI - Transcriptome-wide analysis of alternative RNA splicing events in Epstein-Barr
virus-associated gastric carcinomas.
AB - Multiple human diseases including cancer have been associated with a
dysregulation in RNA splicing patterns. In the current study, modifications to
the global RNA splicing landscape of cellular genes were investigated in the
context of Epstein-Barr virus-associated gastric cancer. Global alterations to
the RNA splicing landscape of cellular genes was examined in a large-scale screen
from 295 primary gastric adenocarcinomas using high-throughput RNA sequencing
data. RT-PCR analysis, mass spectrometry, and co-immunoprecipitation studies were
also used to experimentally validate and investigate the differential alternative
splicing (AS) events that were observed through RNA-seq studies. Our study
identifies alterations in the AS patterns of approximately 900 genes such as
tumor suppressor genes, transcription factors, splicing factors, and kinases.
These findings allowed the identification of unique gene signatures for which AS
is misregulated in both Epstein-Barr virus-associated gastric cancer and EBV
negative gastric cancer. Moreover, we show that the expression of Epstein-Barr
nuclear antigen 1 (EBNA1) leads to modifications in the AS profile of cellular
genes and that the EBNA1 protein interacts with cellular splicing factors. These
findings provide insights into the molecular differences between various types of
gastric cancer and suggest a role for the EBNA1 protein in the dysregulation of
cellular AS.
PMID- 28493892
TI - HIV infection as vascular risk: A systematic review of the literature and meta
analysis.
AB - IMPORTANCE: The vascular risk attributable to HIV infection is rising. The
heterogeneity of the samples studied is an obstacle to understanding whether HIV
is a vascular risk across geographic regions. OBJECTIVE: To test the hypothesis
that HIV infection is a vascular risk factor, and that the risk conferred by HIV
varies by geographical region. DATA SOURCES: A systematic search of publications
was carried out in seven electronic databases: PubMed, The Cochrane Library,
EMBASE, Web of Science, LILACS, ClinicalTrials.gov, and WHO International
Clinical Trials Registry Platform from inception to July 2015. STUDY SELECTION:
We included longitudinal studies of HIV+ individuals and their risk of vascular
outcomes of >= 50 HIV+ cases and excluded studies on biomarkers of vascular
disease as well as clinical trials. DATA EXTRACTION AND SYNTHESIS: Data was
extracted by one of the authors and independently confirmed by the other two
authors. We used incidence rate (IR), incidence risk ratio (IRR) and hazard ratio
(HR) with their 95% confidence intervals as measures of risk. MAIN OUTCOME: All
death, myocardial infarction (MI), coronary heart disease (CHD), any stroke,
ischemic stroke (IS) or intracranial hemorrhage (ICH). RESULTS: We screened
11,482 references for eligibility, and selected 117 for analysis. Forty-four
cohorts represented 334,417 HIV+ individuals, 49% from the United States.
Compared with their European counterparts, HIV+ individuals in the United States
had higher IR of death (IRR 1.78, 1.69-1.88), MI (IRR 1.61, 1.29-2.01), CHD (IRR
2.27, 1.92-2.68), any stroke (IRR 1.94, 1.59-2.38), IS (IRR 1.56, 1.23-1.98), and
ICH (IRR 4.03, 2.72-6.14). Compared with HIV- controls and independent of
geographical region, HIV was a risk for death (HR 4.77, 4.55-5.00), MI (HR 1.60,
1.49-1.72), any CHD (HR 1.20, 1.15-1.25), any stroke (HR 1.82, 1.53-2.16), IS (HR
1.27, 1.15-1.39) and ICH (HR 2.20, 1.61-3.02). Use of antiretroviral therapy was
a consistent risk for cardiac outcomes, while immunosuppression and unsuppressed
viral load were consistent risks for cerebral outcomes. CONCLUSIONS: HIV should
be considered a vascular risk, with varying magnitudes across geographical and
anatomical regions. We think that strategies to reduce the HIV-related vascular
burden are urgent, and should incorporate the disparities noted here.
PMID- 28493893
TI - Comparison of influencing factors on outcomes of single and multiple road traffic
injuries: A regional study in Shanghai, China (2011-2014).
AB - INTRODUCTION: To identify key intervention factors and reduce road traffic injury
(RTI)-associated mortality, this study compared outcomes and influencing factors
of single and multiple road traffic injuries (RTIs) in Shanghai. METHODS: Based
on the design of National Trauma Data Bank, this study collected demographic,
injury, and outcome data from RTI patients treated at the four largest trauma
centers in Shanghai from January 2011 to January 2015. Data were analyzed with
descriptive statistics, univariate analysis, and hierarchical logistic regression
analysis. RESULTS: Among 2397 participants, 59.4% had a single injury, and 40.6%
had multiple injuries. Most patients' outcome was cure or improvement. For single
RTI patients, length of stay, body region, central nervous system injury, acute
renal failure, multiple organ dysfunction syndrome, bacterial infection, and coma
were significantly related to outcome. For multiple-RTI patients, age, admission
pathway, prehospital time, length of stay, number of body regions, body region,
injury condition, injury severity score, and coma were significantly related to
outcome. CONCLUSIONS: Emergency rescue in road traffic accidents should focus on
high-risk groups (the elderly), high-incidence body regions (head, thorax,
pelvis) and number of injuries, injury condition (central nervous system injury,
coma, complications, admission pathway), injury severity (critically injured
patients), and time factors (particularly prehospital time).
PMID- 28493894
TI - Multi-scale temporal patterns in fish presence in a high-velocity tidal channel.
AB - The natural variation of fish presence in high-velocity tidal channels is not
well understood. A better understanding of fish use of these areas would aid in
predicting fish interactions with marine hydrokinetic (MHK) devices, the effects
of which are uncertain but of high concern. To characterize the patterns in fish
presence at a tidal energy site in Cobscook Bay, Maine, we examined two years of
hydroacoustic data continuously collected at the proposed depth of an MHK turbine
with a bottom-mounted, side-looking echosounder. The maximum number of fish
counted per hour ranged from hundreds in the early spring to over 1,000 in the
fall. Counts varied greatly with tidal and diel cycles in a seasonally changing
relationship, likely linked to the seasonally changing fish community of the bay.
In the winter and spring, higher hourly counts were generally confined to ebb
tides and low slack tides near sunrise and sunset. In summer and fall of each
year, the highest fish counts shifted to night and occurred during ebb, low
slack, and flood tides. Fish counts were not linked to current speed, and did not
decrease as current speed increased, contrary to observations at other tidal
power sites. As fish counts may be proportional to the encounter rate of fish
with an MHK turbine at the same depth, highly variable counts indicate that the
risk to fish is similarly variable. The links between fish presence and
environmental cycles at this site will likely be present at other locations with
similar environmental forcing, making these observations useful in predicting
potential fish interactions at tidal energy sites worldwide.
PMID- 28493891
TI - Antibody to HSV gD peptide induced by vaccination does not protect against HSV-2
infection in HSV-2 seronegative women.
AB - BACKGROUND: In the HIV-1 vaccine trial RV144, ALVAC-HIV prime with an AIDSVAX(r)
B/E boost reduced HIV-1 acquisition by 31% at 42 months post first vaccination.
The bivalent AIDSVAX(r) B/E vaccine contains two gp120 envelope glycoproteins,
one from the subtype B HIV-1 MN isolate and one from the subtype CRF01_AE A244
isolate. Each envelope glycoprotein harbors a highly conserved 27-amino acid HSV
1 glycoprotein D (gD) tag sequence that shares 93% sequence identity with the HSV
2 gD sequence. We assessed whether vaccine-induced anti-gD antibodies protected
females against HSV-2 acquisition in RV144. METHODS: Of the women enrolled in
RV144, 777 vaccine and 807 placebo recipients were eligible and randomly selected
according to their pre-vaccination HSV-1 and HSV-2 serostatus for analysis.
Immunoglobulin G (IgG) and IgA responses to gD were determined by a binding
antibody multiplex assay and HSV-2 serostatus was determined by Western blot
analysis. Ninety-three percent and 75% of the vaccine recipients had anti-gD IgG
and IgA responses two weeks post last vaccination, respectively. There was no
evidence of reduction in HSV-2 infection by vaccination compared to placebo
recipients over 78 weeks of follow-up. The annual incidence of HSV-2 infection in
individuals who were HSV-2 negative at baseline or HSV-1 positive and HSV-2
indeterminate at baseline were 4.38/100 person-years (py) and 3.28/100 py in the
vaccine and placebo groups, respectively. Baseline HSV-1 status did not affect
subsequent HSV-2 acquisition. Specifically, the estimated odds ratio of HSV-2
infection by Week 78 for female placebo recipients who were baseline HSV-1
positive (n = 422) vs. negative (n = 1120) was 1.14 [95% confidence interval 0.66
to 1.94, p = 0.64)]. No evidence of reduction in the incidence of HSV-2 infection
by vaccination was detected. CONCLUSIONS: AIDSVAX(r) B/E containing gD did not
confer protection from HSV-2 acquisition in HSV-2 seronegative women, despite
eliciting anti-gD serum antibodies.
PMID- 28493895
TI - The cardiac glycoside ouabain activates NLRP3 inflammasomes and promotes cardiac
inflammation and dysfunction.
AB - Cardiac glycosides such as digoxin are Na+/K+-ATPase inhibitors that are widely
used for the treatment of chronic heart failure and cardiac arrhythmias; however,
recent epidemiological studies have suggested a relationship between digoxin
treatment and increased mortality. We previously showed that nucleotide-binding
oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3)
inflammasomes, which regulate caspase-1-dependent interleukin (IL)-1beta release,
mediate the sterile cardiovascular inflammation. Because the Na+/K+-ATPase is
involved in inflammatory responses, we investigated the role of NLRP3
inflammasomes in the pathophysiology of cardiac glycoside-induced cardiac
inflammation and dysfunction. The cardiac glycoside ouabain induced cardiac
dysfunction and injury in wild-type mice primed with a low dose of
lipopolysaccharide (LPS), although no cardiac dysfunction was observed in mice
treated with either ouabain or LPS alone. Ouabain also induced cardiac
inflammatory responses, such as macrophage infiltration and IL-1beta release,
when mice were primed with LPS. These cardiac manifestations were all
significantly attenuated in mice deficient in IL-1beta. Furthermore, deficiency
of NLRP3 inflammasome components, NLRP3 and caspase-1, also attenuated ouabain
induced cardiac dysfunction and inflammation. In vitro experiments revealed that
ouabain induced NLRP3 inflammasome activation as well as subsequent IL-1beta
release from macrophages, and this activation was mediated by K+ efflux. Our
findings demonstrate that cardiac glycosides promote cardiac inflammation and
dysfunction through NLRP3 inflammasomes and provide new insights into the
mechanisms underlying the adverse effects of cardiac glycosides.
PMID- 28493896
TI - Candidemia in the elderly: What does it change?
AB - BACKGROUND: Candidemia is a life-threatening fungal infection and it can affect
patients of all ages. Characterization of candidemia in the elderly is lacking.
METHODS: We performed a retrospective study of adults (>= 18 years) with
candidemia diagnosed in our center in 2010-2015. Demographics, comorbidities,
clinical and microbiologic characteristics, antifungal treatment and outcome were
compared between older (<=65 years) and younger (>65 years) patients. RESULTS:
Among 302 patients with candidemia identified during the study period, 188 (62%)
belonged to the elderly group. Comorbidities were significantly more frequent in
older patients and included chronic pulmonary diseases, cardiovascular diseases,
diabetes mellitus, and chronic renal failure (p ranging from <0.0001 to 0.017). A
significantly higher proportion of older patients had septic shock (p = 0.040) at
the time of candidemia. Candida albicans accounted for 53% of isolates and there
were no significant differences between patients' age and Candida species. Thirty
day mortality was significantly higher in older (45%) than in younger (28%)
patients (p = 0.003). Factors associated with a significant higher proportion of
death in the elderly included older age (i.e.: old-old), being hospitalized in
ICU rather than in other wards, suffering from chronic pulmonary diseases, the
presence of septic shock, multiple organ failure, dialysis and being infected
with C. glabrata (p ranging from <0.0001 to 0.034). On multivariate analysis
septic shock (HR 1.744 [CI95% 1.049-2.898], p = 0.032) and multiple organ failure
(HR 2.242 [CI95% 1.070-4.698], p = 0.032) were independently associated with a
higher risk of death. The probability of 30-days survival of older patients was
significantly reduced when compared to that of younger patients (p = 0.005) who
did not receive any treatment. In the elderly, there was a trend toward higher
MICs for fluconazole/C. albicans, fluconazole/C. glabrata, amphotericin B/C.
albicans, and caspofungin/C. glabrata. CONCLUSIONS: In our study, we found that
elderly patients with Candida bloodstream infections are characterized by a high
mortality rate. In particular, the lack of any antifungal therapy as well as the
occurrence of septic shock increased significantly the overall mortality.
Additionally, we found that there was a trend of higher MIC for specific
drug/Candida combination.
PMID- 28493897
TI - Characterization of a Bvg-regulated fatty acid methyl-transferase in Bordetella
pertussis.
AB - The whooping cough agent Bordetella pertussis controls the expression of its
large virulence regulon in a coordinated manner through the two-component signal
transduction system BvgAS. In addition to the genes coding for bona fide
virulence factors, the Bvg regulon comprises genes of unknown function. In this
work, we characterized a new Bvg-activated gene called BP2936. Homologs of BP2936
are found in other pathogenic Bordetellae and in several other species, including
plant pathogens and environmental bacteria. We showed that the gene product of
BP2936 is a membrane-associated methyl-transferase of free fatty acids. We thus
propose to name it FmtB, for fatty acid methyl-transferase of Bordetella. The
role of this protein was tested in cellular and animal models of infection, but
the loss of BP2936 did not appear to affect host-pathogen interactions in those
assays. The high level of conservation of BP2936 among B. pertussis isolates
nevertheless argues that it probably plays a role in the life cycle of this
pathogen.
PMID- 28493898
TI - Apathy, but not depression, is associated with executive dysfunction in cerebral
small vessel disease.
AB - OBJECTIVE: To determine the prevalence of apathy and depression in cerebral small
vessel disease (SVD), and the relationships between both apathy and depression
with cognition. To examine whether apathy is specifically related to impairment
in executive functioning and processing speed. METHODS: 196 patients with a
clinical lacunar stroke and an anatomically corresponding lacunar infarct on MRI
were compared to 300 stroke-free controls. Apathy and depression were measured
using the Geriatric Depression Scale, and cognitive functioning was assessed
using an SVD cognitive screening tool, the Brief Memory and Executive Test, which
measures executive functioning/processing speed and memory/orientation. Path
analysis and binary logistic regression were used to assess the relation between
apathy, depression and cognitive impairment. RESULTS: 31 participants with SVD
(15.8%) met criteria for apathy only, 23 (11.8%) for both apathy and depression,
and 2 (1.0%) for depression only. In the SVD group the presence of apathy was
related to global cognition, and specifically to impaired executive
functioning/processing speed, but not memory/orientation. The presence of
depression was not related to global cognition, impaired executive
functioning/processing speed or memory/orientation. CONCLUSIONS: Apathy is a
common feature of SVD and is associated with impaired executive
functioning/processing speed suggesting the two may share biological mechanisms.
Screening for apathy should be considered in SVD, and further work is required to
develop and evaluate effective apathy treatment or management in SVD.
PMID- 28493899
TI - Distinct behavioral and brain changes after different durations of the modified
multiple platform method on rats: An animal model of central fatigue.
AB - The modified multiple platform method (MMPM) is a classical sleep deprivation
model. It has been widely used in behavioral and brain research, due to its
effects on physical and mental functions. However, different MMPM protocols can
promote distinct effects in rats. Although the MMPM has been proved to induce
central fatigue, the effects of different durations of subjection to the MMPM
remain undetermined. This study aims to investigate the changes in behavior, N
Methyl-d-Aspartate receptor 1 (NR1) and 2A (NR2A), as well as the ultrastructural
alteration in the hippocampus after different MMPM modelling, to compare the
central fatigue effect induced by dynamic MMPM. Rats were randomly divided into
four groups: 5-, 14- and 21- day MMPM groups, and a control group. Each MMPM
group underwent a 14-hour daily MMPM modelling. After each training session, open
field and elevated plus maze tests were performed. Corticosterone levels were
detected by ELISA, and the hippocampal NR1 and NR2A were measured by RT-PCR and
Western blot analysis. In addition, ultrastructural changes in the hippocampal
cornu ammonis 1(CA1) region were determined by transmission electron microscopy
(TEM). The findings showed that the 5 and 14 days of MMPM induced a high-stress
state, while the 21 days of MMPM induced anxiety and degenerative alteration in
the hippocampal morphology. Additionally, hippocampal NR1 and NR2A gene
expression decreased in all MMPM groups, whereas the protein expression only
decreased in the 21-day group. Overall, different durations of MMPM caused
distinct behavioral and brain changes, and the 21 days of MMPM could induce
central fatigue.
PMID- 28493901
TI - The feasibility of local participation in Measuring, Reporting and Verification
(PMRV) for REDD.
AB - The studies in this PLOS ONE collection investigated the feasibility of community
participation in Measuring, Reporting and Verifying (Participatory MRV-PMRV)
initiatives in the context of national programs to reduce emissions from
deforestation and forest degradation (REDD+). While such participation is
desirable, its feasibility has been uncertain. This collection builds the
empirical foundations for putting PMRV into practice. The authors of this article
identified five crucial considerations: (1) clarify the stakeholders, (2)
understand their motivation to participate, (3) integrate knowledge and
information from multiple disciplines and sources, (4) convey knowledge and
information across multiple levels of governance, and (5) clarify and enable the
links to REDD+ safeguards. We conclude that local communities and other local
actors can play a major role in achieving REDD+ MRV, however, this requires
attention to their needs and motivations. Future activities should include
assessment of past PMRV experiences, costs and benefits, operationalization of
reporting and verification, formalization of PMRV and full scale testing on the
ground.
PMID- 28493900
TI - Genomic biomarkers of prenatal intrauterine inflammation in umbilical cord tissue
predict later life neurological outcomes.
AB - BACKGROUND: Preterm birth is a major risk factor for neurodevelopmental delays
and disorders. This study aimed to identify genomic biomarkers of intrauterine
inflammation in umbilical cord tissue in preterm neonates that predict cognitive
impairment at 10 years of age. STUDY DESIGN: Genome-wide messenger RNA (mRNA)
levels from umbilical cord tissue were obtained from 43 neonates born before 28
weeks of gestation. Genes that were differentially expressed across four
indicators of intrauterine inflammation were identified and their functions
examined. Exact logistic regression was used to test whether expression levels in
umbilical cord tissue predicted neurocognitive function at 10 years of age.
RESULTS: Placental indicators of inflammation were associated with changes in the
mRNA expression of 445 genes in umbilical cord tissue. Transcripts with decreased
expression showed significant enrichment for biological signaling processes
related to neuronal development and growth. The altered expression of six genes
was found to predict neurocognitive impairment when children were 10 years old
These genes include two that encode for proteins involved in neuronal
development. CONCLUSION: Prenatal intrauterine inflammation is associated with
altered gene expression in umbilical cord tissue. A set of six of the
differentially expressed genes predict cognitive impairment later in life,
suggesting that the fetal environment is associated with significant adverse
effects on neurodevelopment that persist into later childhood.
PMID- 28493902
TI - Circulating levels of sclerostin but not DKK1 associate with laboratory
parameters of CKD-MBD.
AB - INTRODUCTION: Mounting evidence indicates that a disturbed Wnt-beta-catenin
signaling may be involved in the pathogenesis of chronic kidney disease-mineral
and bone and mineral disorder (CKD-MBD). Data on the impact of CKD on circulating
levels of the Wnt antagonists sclerostin and Dickkopf related protein 1 (DKK1)
and the relationship with laboratory parameters of CKD-MBD are incomplete.
METHODS: We analyzed serum sclerostin and DKK1 in 308 patients across the stages
of chronic kidney disease (kDOQI stage 1-2 n = 41; CKD stage 3 n = 54; CKD stage
4-5 n = 54; hemodialysis n = 100; peritoneal dialysis n = 59) as well as in 49
healthy controls. We investigated associations with demographics, renal function,
parameters of mineral metabolism including 25(OH) vitamin D, 1,25(OH)2 vitamin D,
biointact fibroblast growth factor 23 (FGF23), and parathyroid hormone (PTH), and
bone turnover markers. RESULTS: Serum sclerostin, but not DKK1, increases in more
advanced stages of CKD and associates with PTH, phosphate, and 1,25(OH)2 vitamin
D concentrations. Bone turnover markers are highest in hemodialysis patients
presenting the combination of high PTH with low sclerostin level. Serum DKK1
levels are lower in CKD patients than in controls and are not associated with
laboratory parameters of mineral metabolism. Interestingly, a direct association
between DKK1 and platelet count was observed. CONCLUSION: In CKD, serum levels of
the Wnt inhibitors DKK1 and sclerostin are unrelated, indicating different sites
of origin and/ or different regulatory mechanisms. Sclerostin, as opposed to
DKK1, may qualify as a biomarker of CKD-MBD, particularly in dialysis patients.
DKK1 serum levels, remarkably, correlate almost uniquely with blood platelet
counts.
PMID- 28493903
TI - A novel multifunctional peptide oligomer of bacitracin with possible
bioindustrial and therapeutic applications from a Korean food-source Bacillus
strain.
AB - CONCLUSION: CSP32 has stable characteristics and may find bio-industrial and
therapeutic applications.
PMID- 28493904
TI - Factors associated with help-seeking behaviour among individuals with major
depression: A systematic review.
AB - Psychological models can help to understand why many people suffering from major
depression do not seek help. Using the 'Behavioral Model of Health Services Use',
this study systematically reviewed the literature on the characteristics
associated with help-seeking behaviour in adults with major depression. Articles
were identified by systematically searching the MEDLINE, EMBASE and PsycInfo
databases and relevant reference lists. Observational studies investigating the
associations between individual or contextual characteristics and professional
help-seeking behaviour for emotional problems in adults formally diagnosed with
major depression were included. The quality of the included studies was assessed,
and factors associated with help-seeking behaviour were qualitatively
synthesized. In total, 40 studies based on 26 datasets were included. Several
studies investigated predisposing (age (N = 17), gender (N = 16), ethnicity (N =
9), education (N = 11), marital status (N = 12)), enabling (income (N = 12)),
need (severity (N = 14), duration (N = 9), number of depressive episodes (N = 6),
psychiatric comorbidity (N = 10)) and contextual factors (area (N = 8)). Socio
demographic and need factors appeared to influence help-seeking behaviour.
Although existing studies provide insight into the characteristics associated
with help seeking for major depression, cohort studies and research on beliefs
about, barriers to and perceived need for treatment are lacking. Based on this
review, interventions to increase help-seeking behaviour can be designed.
PMID- 28493906
TI - A diffusion based study of population dynamics: Prehistoric migrations into South
Asia.
AB - A diffusion equation has been used to study migration of early humans into the
South Asian subcontinent. The diffusion equation is tempered by a set of
parameters that account for geographical features like proximity to water
resources, altitude, and flatness of land. The ensuing diffusion of populations
is followed in time-dependent computer simulations carried out over a period of
10,000 YBP. The geographical parameters are determined from readily-available
satellite data. The results of our computer simulations are compared to recent
genetic data so as to better correlate the migratory patterns of various
populations; they suggest that the initial populations started to coalesce around
4,000 YBP before the commencement of a period of relative geographical isolation
of each population group. The period during which coalescence of populations
occurred appears consistent with the established timeline associated with the
Harappan civilization and also, with genetic admixing that recent genetic mapping
data reveal. Our results may contribute to providing a timeline for the movement
of prehistoric people. Most significantly, our results appear to suggest that the
Ancestral Austro-Asiatic population entered the subcontinent through an easterly
direction, potentially resolving a hitherto-contentious issue.
PMID- 28493907
TI - Edema is not a reliable diagnostic sign to exclude small brain metastases.
AB - No prior systematic study on the extent of vasogenic edema (VE) in patients with
brain metastases (BM) exists. Here, we aim to determine 1) the general volumetric
relationship between BM and VE, 2) a threshold diameter above which a BM shows
VE, and 3) the influence of the primary tumor and location of the BM in order to
improve diagnostic processes and understanding of edema formation. This single
center, retrospective study includes 173 untreated patients with histologically
proven BM. Semi-manual segmentation of 1416 BM on contrast-enhanced T1-weighted
images and of 865 VE on fluid-attenuated inversion recovery/T2-weighted images
was conducted. Statistical analyses were performed using a paired-samples t-test,
linear regression/generalized mixed-effects model, and receiver-operating
characteristic (ROC) curve controlling for the possible effect of non-uniformly
distributed metastases among patients. For BM with non-confluent edema (n = 545),
there was a statistically significant positive correlation between the volumes of
the BM and the VE (P < 0.001). The optimal threshold for edema formation was a
diameter of 9.4 mm for all BM. The primary tumors as interaction term in
multivariate analysis had a significant influence on VE formation whereas
location had not. Hence VE development is dependent on the volume of the
underlying BM and the site of the primary neoplasm, but not from the location of
the BM.
PMID- 28493908
TI - Missed diagnostic opportunities within South Africa's early infant diagnosis
program, 2010-2015.
AB - BACKGROUND: Samples submitted for HIV PCR testing that fail to yield a positive
or negative result represent missed diagnostic opportunities. We describe HIV PCR
test rejections and indeterminate results, and the associated delay in diagnosis,
within South Africa's early infant diagnosis (EID) program from 2010 to 2015.
METHODS: HIV PCR test data from January 2010 to December 2015 were extracted from
the National Health Laboratory Service Corporate Data Warehouse, a central data
repository of all registered test-sets within the public health sector in South
Africa, by laboratory number, result, date, facility, and testing laboratory.
Samples that failed to yield either a positive or negative result were
categorized according to the rejection code on the laboratory information system,
and descriptive analysis performed using Microsoft Excel. Delay in diagnosis was
calculated for patients who had a missed diagnostic opportunity registered
between January 2013 and December 2015 by means of a patient linking-algorithm
employing demographic details. RESULTS: Between 2010 and 2015, 2 178 582 samples
were registered for HIV PCR testing of which 6.2% (n = 134 339) failed to yield
either a positive or negative result, decreasing proportionally from 7.0% (n = 20
556) in 2010 to 4.4% (n = 21 388) in 2015 (p<0.001). Amongst 76 972 coded missed
diagnostic opportunities, 49 585 (64.4%) were a result of pre-analytical error
and 27 387 (35.6%) analytical error. Amongst 49 694 patients searched for follow
up results, 16 895 (34.0%) had at least one subsequent HIV PCR test registered
after a median of 29 days (IQR: 13-57), of which 8.4% tested positive compared
with 3.6% of all samples submitted for the same period. CONCLUSIONS: Routine
laboratory data provides the opportunity for near real-time surveillance and
quality improvement within the EID program. Delay in diagnosis and wastage of
resources associated with missed diagnostic opportunities must be addressed and
infants actively followed-up as South Africa works towards elimination of mother
to-child transmission.
PMID- 28493905
TI - Melioidosis: Clinical impact and public health threat in the tropics.
AB - This review briefly summarizes the geographical distribution and clinical impact
of melioidosis, especially in the tropics. Burkholderia pseudomallei (a gram
negative bacterium) is the major causative agent for melioidosis, which is
prevalent in Singapore, Malaysia, Thailand, Vietnam, and Northern Australia.
Melioidosis patients are increasingly being recognized in other parts of the
world. The bacteria are intrinsically resistant to many antimicrobial agents, but
prolonged treatment, especially with combinations of antibiotics, may be
effective. Despite therapy, the overall case fatality rate of septicemia in
melioidosis remains significantly high. Intracellular survival of the bacteria
within macrophages may progress to chronic infections, and about 10% of patients
suffer relapses. In the coming decades, melioidosis will increasingly afflict
travelers throughout many global regions. Clinicians managing travelers returning
from the subtropics or tropics with severe pneumonia or septicemia should
consider acute melioidosis as a differential diagnosis. Patients with open skin
wounds, diabetes, or chronic renal disease are at higher risk for melioidosis and
should avoid direct contact with soil and standing water in endemic regions.
Furthermore, there are fears that B. pseudomallei may be used as a biological
weapon. Technological advancements in molecular diagnostics and antibiotic
therapy are improving the disease outcomes in endemic areas throughout Asia.
Research and development efforts on vaccine candidates against melioidosis are
ongoing.
PMID- 28493909
TI - HNF1alpha defect influences post-prandial lipid regulation.
AB - PURPOSE: Hepatocyte nuclear factor 1 alpha (HNF1alpha) defects cause Mature Onset
Diabetes of the Young type 3 (MODY3), characterized by defects in beta-cell
insulin secretion. However, HNF1alpha is involved in many other metabolic
pathways with relevance for monogenic or polygenic type 2 diabetes. We aimed to
investigate gut hormones, lipids, and insulin regulation in response to a meal
test in HNF1alpha defect carriers (MODY3) compared to non-diabetic subjects
(controls) and type 2 diabetes (T2D). METHODS: We administered a standardized
liquid meal to each participant. Over 6 hours, we measured post-meal responses of
insulin regulation (blood glucose, c-peptide, insulin), gut hormones (ghrelin,
glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1) and lipids
(non-esterified fatty acids [NEFA] and triglycerides). RESULTS: We found that
MODY3 participants had lower insulin secretion indices than controls and T2D
participants, showing the expected beta-cell defect. MODY3 had similar glycated
hemoglobin levels (HbA1c median [IQR]: 6.5 [5.6-7.6]%) compared to T2D (median:
6.6 [6.2-6.9]%; P<0.05). MODY3 had greater insulin sensitivity (Matsuda index:
71.9 [29.6; 125.5]) than T2D (3.2 [4.0; 6.0]; P<0.05). MODY3 experienced a larger
decrease in the ratio of NEFA to insulin (NEFA 30-0 / insulin 30-0: -39 [-78;
30] x104) in the early post-prandial period (0-30 minutes) compared to controls
and to T2D (-2.0 [-0.6; -6.4] x104; P<0.05). MODY3 had lower fasting (0.66 [0.46;
1.2] mM) and post-meal triglycerides levels compared to T2D (fasting: 2.3 [1.7;
2.7] mM; P<0.05). We did not detect significant post-meal differences in ghrelin
and incretins between MODY3 and other groups. CONCLUSION: In response to a
standard meal test, MODY3 showed greater early post-prandial NEFA diminution in
response to relatively low early insulin secretion, and they maintained very low
post-prandial triglycerides levels.
PMID- 28493910
TI - A new two-stage method for revealing missing parts of edges in protein-protein
interaction networks.
AB - With the increasing availability of high-throughput data, various computational
methods have recently been developed for understanding the cell through protein
protein interaction (PPI) networks at a systems level. However, due to the
incompleteness of the original PPI networks those efforts have been significantly
hindered. In this paper, we propose a two stage method to predict underlying
links between two originally unlinked protein pairs. First, we measure gene
expression and gene functional similarly between unlinked protein pairs on
Saccharomyces cerevisiae benchmark network and obtain new constructed networks.
Then, we select the significant part of the new predicted links by analyzing the
difference between essential proteins that have been identified based on the new
constructed networks and the original network. Furthermore, we validate the
performance of the new method by using the reliable and comprehensive PPI dataset
obtained from the STRING database and compare the new proposed method with four
other random walk-based methods. Comparing the results indicates that the new
proposed strategy performs well in predicting underlying links. This study
provides a general paradigm for predicting new interactions between protein pairs
and offers new insights into identifying essential proteins.
PMID- 28493911
TI - Long-term fertilization determines different metabolomic profiles and responses
in saplings of three rainforest tree species with different adult canopy
position.
AB - BACKGROUND: Tropical rainforests are frequently limited by soil nutrient
availability. However, the response of the metabolic phenotypic plasticity of
trees to an increase of soil nutrient availabilities is poorly understood. We
expected that increases in the ability of a nutrient that limits some plant
processes should be detected by corresponding changes in plant metabolome profile
related to such processes. METHODOLOGY/PRINCIPAL FINDINGS: We studied the foliar
metabolome of saplings of three abundant tree species in a 15 year field NPK
fertilization experiment in a Panamanian rainforest. The largest differences were
among species and explained 75% of overall metabolome variation. The saplings of
the large canopy species, Tetragastris panamensis, had the lowest concentrations
of all identified amino acids and the highest concentrations of most identified
secondary compounds. The saplings of the "mid canopy" species, Alseis blackiana,
had the highest concentrations of amino acids coming from the biosynthesis
pathways of glycerate-3P, oxaloacetate and alpha-ketoglutarate, and the saplings
of the low canopy species, Heisteria concinna, had the highest concentrations of
amino acids coming from the pyruvate synthesis pathways.
CONCLUSIONS/SIGNIFICANCE: The changes in metabolome provided strong evidence that
different nutrients limit different species in different ways. With increasing P
availability, the two canopy species shifted their metabolome towards larger
investment in protection mechanisms, whereas with increasing N availability, the
sub-canopy species increased its primary metabolism. The results highlighted the
proportional distinct use of different nutrients by different species and the
resulting different metabolome profiles in this high diversity community are
consistent with the ecological niche theory.
PMID- 28493912
TI - Effects of intensity and amount of exercise on measures of insulin and glucose:
Analysis of inter-individual variability.
AB - AIM: To determine the separate effects of exercise amount and intensity on the
rate of response for glucose and insulin variables, where rate of response was
defined as the number of individuals with improvement in glucose and insulin
values that was beyond the day-to-day variability of measurement. METHODS:
Participants were 171 sedentary, middle-aged abdominally obese adults who
completed a 24-week intervention. Participants were randomly assigned to (1) no
exercise control (n = 51), (2) low-amount, low-intensity exercise (LALI, n = 38),
(3) high-amount, low-intensity exercise (HALI, n = 52), or (4) high-amount, high
intensity exercise (HAHI, n = 30). Two-hour glucose, insulin area under the curve
(AUC), and fasting insulin were measured during a 2-hour, 75g oral glucose
challenge. The day-to-day variability for these measures was calculated to be +/
2.2 mmol/L, +/-940.2 pmol/L, and +/-38.9 pmol/L, respectively. RESULTS: At 24
weeks, the number of nonresponders for 2-hr glucose was 98.0%, 86.8%, 94.2%,
86.7% in the control, LALI, HALI, and HAHI groups, respectively. The number of
nonresponders for insulin AUC was 88.0%, 75.7%, 75.0%, 80.0% in the control,
LALI, HALI, and HAHI groups, respectively. The number of nonresponders for
fasting insulin was 88.2%, 84.2%, 84.6%, 93.3% in the control, LALI, HALI, and
HAHI groups, respectively. The rate of response was not different between control
and any of the exercise groups for any measure (p>0.05). CONCLUSION: The
improvement in glucose and insulin measures did not exceed the day-to-day
variability of measurement for approximately 80% of the participants independent
of exercise amount or intensity.
PMID- 28493914
TI - Take me where I want to go: Institutional prestige, advisor sponsorship, and
academic career placement preferences.
AB - Placement in prestigious research institutions for STEM (science, technology,
engineering, and mathematics) PhD recipients is generally considered to be
optimal. Yet some doctoral recipients are not interested in intensive research
careers and instead seek alternative careers, outside but also within academe
(for example teaching positions in Liberal Arts Schools). Recent attention to non
academic pathways has expanded our understanding of alternative PhD careers.
However, career preferences and placements are also nuanced along the academic
pathway. Existing research on academic careers (mostly research-centric) has
found that certain factors have a significant impact on the prestige of both the
institutional placement and the salary of PhD recipients. We understand less,
however, about the functioning of career preferences and related placements
outside of the top academic research institutions. Our work builds on prior
studies of academic career placement to explore the impact that prestige of PhD
granting institution, advisor involvement, and cultural capital have on the
extent to which STEM PhDs are placed in their preferred academic institution
types. What determines whether an individual with a preference for research
oriented institutions works at a Research Extensive university? Or whether an
individual with a preference for teaching works at a Liberal Arts college? Using
survey data from a nationally representative sample of faculty in biology,
biochemistry, civil engineering and mathematics at four different Carnegie
Classified institution types (Research Extensive, Research Intensive, Master's I
& II, and Liberal Arts Colleges), we examine the relative weight of different
individual and institutional characteristics on institutional type placement. We
find that doctoral institutional prestige plays a significant role in matching
individuals with their preferred institutional type, but that advisor involvement
only has an impact on those with a preference for research oriented institutions.
Gender effects are also observed, particularly in the role of the advisor in
affecting preferred career placement.
PMID- 28493915
TI - An African grassland responds similarly to long-term fertilization to the Park
Grass experiment.
AB - We compared the results of a long-term (65 years) experiment in a South African
grassland with the world's longest-running ecological experiment, the Park Grass
study at Rothamsted, U.K. The climate is warm and humid in South Africa and cool
and temperate in England. The African grassland has been fertilized with two
forms of nitrogen applied at four levels, phosphorus and lime in a crossed design
in 96 plots. In 1951, about 84% of plant cover consisted of Themeda triandra,
Tristachya leucothrix and Setaria nigrirostris. Currently, the dominant species
are Panicum maximum, Setaria sphacelata and Eragrostis curvula, making up 71% of
total biomass. As in the Park Grass experiment, we found a significant (additive)
interaction effect on ANPP of nitrogen and phosphorus, and a (marginally
significant) negative correlation between ANPP and species richness. Unlike the
Park Grass experiment, there was no correlation between ANPP and species richness
when pH was included as a covariate. There was also a significant negative effect
of nitrogen amount and nitrogen form and a positive effect of lime on species
richness and species diversity. Soil pH had an important effect on species
richness. Liming was insufficient to balance the negative effects on species
richness of nitrogen fertilization. There was a significant effect of pH on
biomass of three abundant species. There were also significant effects of light
on the biomass of four species, with only Panicum maximum having a negative
response to light. In all of the abundant species, adding total species richness
and ANPP to the model increased the amount of variance explained. The biomass of
Eragrostis curvula and P. maximum were negatively correlated with species
richness while three other abundant species increased with species richness,
suggesting that competition and facilitation were active. Consistent with the
results from the Park Grass and other long-term fertilization experiments of
grasslands, we found a positive effect of soil pH and a negative effect of
nitrogen amount on species richness, a more acutely negative effect on species
richness of acidic ammonium sulphate fertilizer than limestone ammonium nitrate,
a negative relationship between species richness and biomass, and a positive
effect on species richness of lime interacting with nitrogen.
PMID- 28493913
TI - Pathogenic variants screening in seventeen candidate genes on 2p15 for
association with ankylosing spondylitis in a Han Chinese population.
AB - OBJECTIVES: Previous studies have found the association between rs10865331 in
2p15 area and ankylosing spondylitis (AS). This study aimed to identify
additional functional genetic variants in 2p15 region associated with AS
susceptibility. METHODS: We used next generation sequencing (NGS) in 100 AS cases
and 100 healthy controls to screen AS susceptible genetic variants, and validated
these variants in 620 cases and 620 controls by using imLDRTM technique for
single nucleotide polymorphism (SNP) genotyping. RESULTS: Totally, we identified
12 SNPs that might confer susceptibility to AS. Of those SNPs, three (rs14170,
rs2123111 and rs1729674) were nominally associated (P<0.05) with AS, but were no
longer statistically significant after Bonferroni correction. After stratified by
gender, another two SNPs (rs11428092 and rs10208769 in USP34) were associated
with AS in males but not females, though this was not statistically significant
after Bonferroni correction. In addition, rs1729674, rs14170, rs2123111 and
rs10208769 were in strong linkage disequilibrium (LD) and were further enrolled
in haplotype analysis. A novel haplotype TAGA was found to be associated with a
decreased risk of AS (odds ratio (OR) (95% confidence interval (CI)) = 0.832
(0.705-0.982)). Beyond that, we also demonstrated a strong relationship between
rs10865331 and AS susceptibility (OR (95% CI) = 1.303(1.111-1.526)). CONCLUSIONS:
rs14170 and rs2123111 inUSP34 and rs1729674 in C2orf74 may be associated with AS
susceptibility in Han Chinese population. USP34 and C2orf74 in 2p15 region may be
AS novel susceptibility genes.
PMID- 28493916
TI - Vesicular glutamate transporters play a role in neuronal differentiation of
cultured SVZ-derived neural precursor cells.
AB - The role of glutamate in the regulation of neurogenesis is well-established, but
the role of vesicular glutamate transporters (VGLUTs) and excitatory amino acid
transporters (EAATs) in controlling adult neurogenesis is unknown. Here we
investigated the implication of VGLUTs in the differentiation of subventricular
zone (SVZ)-derived neural precursor cells (NPCs). Our results show that NPCs
express VGLUT1-3 and EAAT1-3 both at the mRNA and protein level. Their expression
increases during differentiation closely associated with the expression of marker
genes. In expression analyses we show that VGLUT1 and VGLUT2 are preferentially
expressed by cultured SVZ-derived doublecortin+ neuroblasts, while VGLUT3 is
found on GFAP+ glial cells. In cultured NPCs, inhibition of VGLUT by Evans Blue
increased the mRNA level of neuronal markers doublecortin, B3T and MAP2, elevated
the number of NPCs expressing doublecortin protein and promoted the number of
cells with morphological appearance of branched neurons, suggesting that VGLUT
function prevents neuronal differentiation of NPCs. This survival- and
differentiation-promoting effect of Evans blue was corroborated by increased AKT
phosphorylation and reduced MAPK phosphorylation. Thus, under physiological
conditions, VGLUT1-3 inhibition, and thus decreased glutamate exocytosis, may
promote neuronal differentiation of NPCs.
PMID- 28493917
TI - The impact of HCV therapy in a high HIV-HCV prevalence population: A modeling
study on people who inject drugs in Ho Chi Minh City, Vietnam.
AB - BACKGROUND: Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV)
coinfection is a major global health problem especially among people who inject
drugs (PWID), with significant clinical implications. Mathematical models have
been used to great effect to shape HIV care, but few have been proposed for
HIV/HCV. METHODS: We constructed a deterministic compartmental ODE model that
incorporated layers for HIV disease progression, HCV disease progression and PWID
demography. Antiretroviral therapy (ART) and Methadone Maintenance Therapy (MMT)
scale-ups were modeled as from 2016 and projected forward 10 years. HCV treatment
roll-out was modeled beginning in 2026, after a variety of MMT scale-up
scenarios, and projected forward 10 years. RESULTS: Our results indicate that
scale-up of ART has a major impact on HIV though not on HCV burden. MMT scale-up
has an impact on incidence of both infections. HCV treatment roll-out has a
measurable impact on reductions of deaths, increasing multifold the mortality
reductions afforded by just ART/MMT scale-ups. CONCLUSION: HCV treatment roll-out
can have major and long-lasting effects on averting PWID deaths on top of those
averted by ART/MMT scale-up. Efficient intervention scale-up of HCV alongside HIV
interventions is critical in Vietnam.
PMID- 28493918
TI - Using null models to infer microbial co-occurrence networks.
AB - Although microbial communities are ubiquitous in nature, relatively little is
known about the structural and functional roles of their constituent organisms'
underlying interactions. A common approach to study such questions begins with
extracting a network of statistically significant pairwise co-occurrences from a
matrix of observed operational taxonomic unit (OTU) abundances across sites. The
structure of this network is assumed to encode information about ecological
interactions and processes, resistance to perturbation, and the identity of
keystone species. However, common methods for identifying these pairwise
interactions can contaminate the network with spurious patterns that obscure true
ecological signals. Here, we describe this problem in detail and develop a
solution that incorporates null models to distinguish ecological signals from
statistical noise. We apply these methods to the initial OTU abundance matrix and
to the extracted network. We demonstrate this approach by applying it to a large
soil microbiome data set and show that many previously reported patterns for
these data are statistical artifacts. In contrast, we find the frequency of three
way interactions among microbial OTUs to be highly statistically significant.
These results demonstrate the importance of using appropriate null models when
studying observational microbiome data, and suggest that extracting and
characterizing three-way interactions among OTUs is a promising direction for
unraveling the structure and function of microbial ecosystems.
PMID- 28493919
TI - Genomic variation in Plasmodium vivax malaria reveals regions under selective
pressure.
AB - BACKGROUND: Although Plasmodium vivax contributes to almost half of all malaria
cases outside Africa, it has been relatively neglected compared to the more
deadly P. falciparum. It is known that P. vivax populations possess high genetic
diversity, differing geographically potentially due to different vector species,
host genetics and environmental factors. RESULTS: We analysed the high-quality
genomic data for 46 P. vivax isolates spanning 10 countries across 4 continents.
Using population genetic methods we identified hotspots of selection pressure,
including the previously reported MRP1 and DHPS genes, both putative drug
resistance loci. Extra copies and deletions in the promoter region of another
drug resistance candidate, MDR1 gene, and duplications in the Duffy binding
protein gene (PvDBP) potentially involved in erythrocyte invasion, were also
identified. For surveillance applications, continental-informative markers were
found in putative drug resistance loci, and we show that organellar polymorphisms
could classify P. vivax populations across continents and differentiate between
Plasmodia spp. CONCLUSIONS: This study has shown that genomic diversity that lies
within and between P. vivax populations can be used to elucidate potential drug
resistance and invasion mechanisms, as well as facilitate the molecular barcoding
of the parasite for surveillance applications.
PMID- 28493920
TI - Haemolytic activity of soil from areas of varying podoconiosis endemicity in
Ethiopia.
AB - BACKGROUND: Podoconiosis, non-filarial elephantiasis, is a non-infectious disease
found in tropical regions such as Ethiopia, localized in highland areas with
volcanic soils cultivated by barefoot subsistence farmers. It is thought that
soil particles can pass through the soles of the feet and taken up by the
lymphatic system, leading to the characteristic chronic oedema of the lower legs
that becomes disfiguring and disabling over time. METHODS: The close association
of the disease with volcanic soils led us to investigate the characteristics of
soil samples in an endemic area in Ethiopia to identify the potential causal
constituents. We used the in vitro haemolysis assay and compared haemolytic
activity (HA) with soil samples collected in a non-endemic region of the same
area in Ethiopia. We included soil samples that had been previously
characterized, in addition we present other data describing the characteristics
of the soil and include pure phase mineral standards as comparisons. RESULTS: The
bulk chemical composition of the soils were statistically significantly different
between the podoconiosis-endemic and non-endemic areas, with the exception of CaO
and Cr. Likewise, the soil mineralogy was statistically significant for iron
oxide, feldspars, mica and chlorite. Smectite and kaolinite clays were widely
present and elicited a strong HA, as did quartz, in comparison to other mineral
phases tested, although no strong difference was found in HA between soils from
the two areas. The relationship was further investigated with principle component
analysis (PCA), which showed that a combination of an increase in Y, Zr and
Al2O3, and a concurrent increase Fe2O3, TiO2, MnO and Ba in the soils increased
HA. CONCLUSION: The mineralogy and chemistry of the soils influenced the HA,
although the interplay between the components is complex. Further research should
consider the variable biopersistance, hygroscopicity and hardness of the minerals
and further characterize the nano-scale particles.
PMID- 28493921
TI - Mapping the emotional face. How individual face parts contribute to successful
emotion recognition.
AB - Which facial features allow human observers to successfully recognize expressions
of emotion? While the eyes and mouth have been frequently shown to be of high
importance, research on facial action units has made more precise predictions
about the areas involved in displaying each emotion. The present research
investigated on a fine-grained level, which physical features are most relied on
when decoding facial expressions. In the experiment, individual faces expressing
the basic emotions according to Ekman were hidden behind a mask of 48 tiles,
which was sequentially uncovered. Participants were instructed to stop the
sequence as soon as they recognized the facial expression and assign it the
correct label. For each part of the face, its contribution to successful
recognition was computed, allowing to visualize the importance of different face
areas for each expression. Overall, observers were mostly relying on the eye and
mouth regions when successfully recognizing an emotion. Furthermore, the
difference in the importance of eyes and mouth allowed to group the expressions
in a continuous space, ranging from sadness and fear (reliance on the eyes) to
disgust and happiness (mouth). The face parts with highest diagnostic value for
expression identification were typically located in areas corresponding to action
units from the facial action coding system. A similarity analysis of the
usefulness of different face parts for expression recognition demonstrated that
faces cluster according to the emotion they express, rather than by low-level
physical features. Also, expressions relying more on the eyes or mouth region
were in close proximity in the constructed similarity space. These analyses help
to better understand how human observers process expressions of emotion, by
delineating the mapping from facial features to psychological representation.
PMID- 28493922
TI - Comparison of the long-term clinical performance of a biodegradable and a
titanium fixation system in maxillofacial surgery: A multicenter randomized
controlled trial.
AB - BACKGROUND: Biodegradable fixation systems could reduce or eliminate problems
associated with titanium removal of implants in a second operation. AIM: The aim
of this study was to compare the long-term (i.e. >5 years postoperatively)
clinical performance of a titanium and a biodegradable system in oral and
maxillofacial surgery. MATERIALS AND METHODS: The present multicenter Randomized
Controlled Trial (RCT) was performed in four hospitals in the Netherlands.
Patients treated with a bilateral sagittal split osteotomy (BSSO) and/or a Le
Fort-I osteotomy, and those treated for fractures of the mandible, maxilla, or
zygoma were included from December 2006 to July 2009. The patients were randomly
assigned to either a titanium (KLS Martin) or a biodegradable group (Inion CPS).
RESULTS: After >5 years postoperatively, plate removal was performed in 22 of the
134 (16.4%) patients treated with titanium and in 23 of the 87 (26.4%) patients
treated with the biodegradable system (P = 0.036, hazard ratio (HR) biodegradable
(95% CI) = 2.0 (1.05-3.8), HR titanium = 1). Occlusion, VAS pain scores, and MFIQ
showed good and (almost) pain free mandibular function in both groups.
CONCLUSION: In conclusion, the performance of the Inion CPS biodegradable system
was inferior compared to the KLS Martin titanium system regarding plate/screws
removal in the abovementioned surgical procedures. TRIAL REGISTRATION:
http://controlled-trials.com ISRCTN44212338.
PMID- 28493923
TI - Brief relaxation training is not sufficient to alter tolerance to experimental
pain in novices.
AB - Relaxation techniques, such as deep breathing and muscle relaxation, are aspects
common to most forms of mindfulness training. There is now an abundance of
research demonstrating that mindfulness training has beneficial effects across a
wide range of clinical conditions, making it an important tool for clinical
intervention. One area of extensive research is on the beneficial effects of
mindfulness on experiences of pain. However, the mechanisms of these effects are
still not well understood. One hypothesis is that the relaxation components of
mindfulness training, through alterations in breathing and muscle tension, leads
to changes in parasympathetic and sympathetic nervous system functioning which
influences pain circuits. The current study seeks to examine how two of the
relaxation subcomponents of mindfulness training, deep breathing and muscle
relaxation, influence experiences of pain in healthy individuals. Participants
were randomized to either a 10 minute deep breathing, progressive muscle
relaxation, or control condition after which they were exposed to a cold pain
task. Throughout the experiment, measures of parasympathetic and sympathetic
nervous system activity were collected to assess how deep breathing and
progressive muscle relaxation alter physiological responses, and if these changes
moderate any effects of these interventions on responses to pain. There were no
differences in participants' pain tolerances or self-reported pain ratings during
the cold pain task or in participants' physiological responses to the task.
Additionally, individual differences in physiological functioning were not
related to differences in pain tolerance or pain ratings. Overall this study
suggests that the mechanisms through which mindfulness exerts its effects on pain
are more complex than merely through physiological changes brought about by
altering breathing or muscle tension. This indicates a need for more research
examining the specific subcomponents of mindfulness, and how these subcomponents
might be acting, to better understand their utility as a clinical treatment.
PMID- 28493924
TI - Cognitive function in multiple sclerosis improves with telerehabilitation:
Results from a randomized controlled trial.
AB - : Cognitive impairment affects more than half of all individuals living with
multiple sclerosis (MS). We hypothesized that training at home with an adaptive
online cognitive training program would have greater cognitive benefit than
ordinary computer games in cognitively-impaired adults with MS. This was a double
blind, randomized, active-placebo-controlled trial. Participants with MS were
recruited through Stony Brook Medicine and randomly assigned to either the
adaptive cognitive remediation (ACR) program or active control of ordinary
computer games for 60 hours over 12 weeks. Training was remotely-supervised and
delivered through a study-provided laptop computer. A computer generated, blocked
stratification table prepared by statistician provided the randomization schedule
and condition was assigned by a study technician. The primary outcome,
administered by study psychometrician, was measured by change in a
neuropsychological composite measure from baseline to study end. An intent-to
treat analysis was employed and missing primary outcome values were imputed via
Markov Chain Monte Carlo method. Participants in the ACR (n = 74) vs. active
control (n = 61) training program had significantly greater improvement in the
primary outcome of cognitive functioning (mean change in composite z score+/-SD:
0.25+/-0.45 vs. 0.09+/-0.37, p = 0.03, estimated difference = 0.16 with 95% CI:
0.02-0.30), despite greater training time in the active control condition (mean+/
SD:56.9 +/- 34.6 vs. 37.7 +/-23 .8 hours played, p = 0.006). This study provides
Class I evidence that adaptive, computer-based cognitive remediation accessed
from home can improve cognitive functioning in MS. This telerehabilitation
approach allowed for rapid recruitment and high compliance, and can be readily
applied to other neurological conditions associated with cognitive dysfunction.
TRIAL REGISTRATION: Clinicaltrials.gov NCT02141386.
PMID- 28493925
TI - A novel Filamentous Flower mutant suppresses brevipedicellus developmental
defects and modulates glucosinolate and auxin levels.
AB - BREVIPEDICELLUS (BP) encodes a class-I KNOTTED1-like homeobox (KNOX)
transcription factor that plays a critical role in conditioning a replication
competent state in the apical meristem, and it also governs growth and cellular
differentiation in internodes and pedicels. To search for factors that modify BP
signaling, we conducted a suppressor screen on bp er (erecta) plants and
identified a mutant that ameliorates many of the pleiotropic defects of the
parent line. Map based cloning and complementation studies revealed that the
defect lies in the FILAMENTOUS FLOWER (FIL) gene, a member of the YABBY family of
transcriptional regulators that contribute to meristem organization and function,
phyllotaxy, leaf and floral organ growth and polarity, and are also known to
repress KNOX gene expression. Genetic and cytological analyses of the fil-10
suppressor line indicate that the role of FIL in promoting growth is independent
of its previously characterized influences on meristem identity and lateral organ
polarity, and likely occurs non-cell-autonomously from superior floral organs.
Transcription profiling of inflorescences revealed that FIL downregulates
numerous transcription factors which in turn may subordinately regulate
inflorescence architecture. In addition, FIL, directly or indirectly, activates
over a dozen genes involved in glucosinolate production in part by activating
MYB28, a known activator of many aliphatic glucosinolate biosynthesis genes. In
the bp er fil-10 suppressor mutant background, enhanced expression of CYP71A13,
AMIDASE1 (AMI) and NITRILASE genes suggest that auxin levels can be modulated by
shunting glucosinolate metabolites into the IAA biosynthetic pathway, and
increased IAA levels in the bp er fil-10 suppressor accompany enhanced internode
and pedicel elongation. We propose that FIL acts to oppose KNOX1 gene function
through a complex regulatory network that involves changes in secondary
metabolites and auxin.
PMID- 28493926
TI - Obesity and access to kidney transplantation in patients starting dialysis: A
prospective cohort study.
AB - BACKGROUND: Obesity has been linked to poor access to medical care. Although
scientific evidence suggest that kidney transplantation improves survival and
quality of life in obese patients with end-stage renal disease (ESRD), few data
exist on the impact of obesity on access to kidney transplantation in this
population. OBJECTIVES: We aimed to characterize the relationships between body
mass index (BMI) at the start of dialysis, changes in BMI after the start of
dialysis, and either access to kidney transplantation or overall mortality in
dialysis or transplantation among ESRD patients. METHODS: Between 2002 and 2011,
19524 dialysis patients with ESRD were included in the study via the French
nationwide Renal Epidemiology and Information Network. Data on sociodemographic
factors, comorbidities and laboratory test results were recorded upon entry into
the registry. BMI were obtained at the start of dialysis and then yearly. Cubic
spline regression analyses provided a graphic evaluation of the relationships
between BMI at the start of dialysis and outcomes. Joint models were used to
evaluate the association between the change over time in BMI and outcomes.
RESULTS: During a median follow-up of 20.3 months, 6634 patients underwent kidney
transplantation. A BMI >31 kg/m2 at the start of the dialysis was associated with
a lower likelihood of receiving a kidney transplant, and the likelihood decreased
even further with higher BMI values. For patients with BMI >=30kg/m2 at the start
of the dialysis, a 1 kg/m2 decrease in BMI during follow-up was associated with a
9% to 11% increase in the likelihood of receiving a transplant. There was an L
shaped relationship between BMI at the start of dialysis and overall mortality.
We showed that obese patients with ESRD face barriers to the receipt of a kidney
transplant without valid reasons. CONCLUSION: Greater attention to this issue
would improve the fairness of the organ allocation process and might improve
outcomes for obese patients with ESRD.
PMID- 28493928
TI - NMR quantification of diffusional exchange in cell suspensions with relaxation
rate differences between intra and extracellular compartments.
AB - Water transport across cell membranes can be measured non-invasively with
diffusion NMR. We present a method to quantify the intracellular lifetime of
water in cell suspensions with short transverse relaxation times, T2, and also
circumvent the confounding effect of different T2 values in the intra- and
extracellular compartments. Filter exchange spectroscopy (FEXSY) is specifically
sensitive to exchange between compartments with different apparent diffusivities.
Our investigation shows that FEXSY could yield significantly biased results if
differences in T2 are not accounted for. To mitigate this problem, we propose
combining FEXSY with diffusion-relaxation correlation experiment, which can
quantify differences in T2 values in compartments with different diffusivities.
Our analysis uses a joint constrained fitting of the two datasets and considers
the effects of diffusion, relaxation and exchange in both experiments. The method
is demonstrated on yeast cells with and without human aquaporins.
PMID- 28493927
TI - Protective effects and functional mechanisms of Lactobacillus gasseri SBT2055
against oxidative stress.
AB - Lactobacillus gasseri SBT2055 (LG2055) is one of the probiotic lactic acid
bacteria. Recently, we demonstrated that feeding with LG2055 extended the
lifespan of Caenorhabditis elegans and that the prolongevity effect was dependent
upon the regulation of oxidative stress response. In this study, we assessed
whether LG2055 regulated the oxidative stress response of mammalian cells. In NIH
3T3 cells and primary mouse embryonic fibroblast cells, low cell proliferation
rates and high reactive oxygen species levels were observed following paraquat
treatment. LG2055 treatment suppressed these responses in paraquat-treated cells,
indicating that LG2055 protected against oxidative stress in mammalian cells. The
mRNA expression of oxidative stress-related genes, total nuclear factor-erythroid
2-related factor 2 (Nrf2) protein levels, and the nuclear translocation of Nrf2
were increased by LG2055 treatment. These results suggested that the Nrf2
antioxidant response element (ARE) signaling pathway was activated by LG2055.
Furthermore, c-Jun NH2-terminal kinase (JNK) was activated by LG2055 treatment
and the inhibition of JNK suppressed the activation of the Nrf2-ARE signaling
pathway in LG2055-treated cells. Together, these findings suggest that LG2055
activated the Nrf2-ARE signaling pathway by JNK activation, thus strengthening
the defense system against oxidative stress in mammalian cells.
PMID- 28493929
TI - Selecting the best stable isotope mixing model to estimate grizzly bear diets in
the Greater Yellowstone Ecosystem.
AB - Past research indicates that whitebark pine seeds are a critical food source for
Threatened grizzly bears (Ursus arctos) in the Greater Yellowstone Ecosystem
(GYE). In recent decades, whitebark pine forests have declined markedly due to
pine beetle infestation, invasive blister rust, and landscape-level fires. To
date, no study has reliably estimated the contribution of whitebark pine seeds to
the diets of grizzlies through time. We used stable isotope ratios (expressed as
delta13C, delta15N, and delta34S values) measured in grizzly bear hair and their
major food sources to estimate the diets of grizzlies sampled in Cooke City
Basin, Montana. We found that stable isotope mixing models that included
different combinations of stable isotope values for bears and their foods
generated similar proportional dietary contributions. Estimates generated by our
top model suggest that whitebark pine seeds (35+/-10%) and other plant foods
(56+/-10%) were more important than meat (9+/-8%) to grizzly bears sampled in the
study area. Stable isotope values measured in bear hair collected elsewhere in
the GYE and North America support our conclusions about plant-based foraging. We
recommend that researchers consider model selection when estimating the diets of
animals using stable isotope mixing models. We also urge researchers to use the
new statistical framework described here to estimate the dietary responses of
grizzlies to declines in whitebark pine seeds and other important food sources
through time in the GYE (e.g., cutthroat trout), as such information could be
useful in predicting how the population will adapt to future environmental
change.
PMID- 28493930
TI - Clinical laboratory reference values amongst children aged 4 weeks to 17 months
in Kilifi, Kenya: A cross sectional observational study.
AB - Reference intervals for clinical laboratory parameters are important for
assessing eligibility, toxicity grading and management of adverse events in
clinical trials. Nonetheless, haematological and biochemical parameters used for
clinical trials in sub-Saharan Africa are typically derived from industrialized
countries, or from WHO references that are not region-specific. We set out to
establish community reference values for haematological and biochemical
parameters amongst children aged 4 weeks to 17 months in Kilifi, Kenya. We
conducted a cross sectional study nested within phase II and III trials of RTS, S
malaria vaccine candidate. We analysed 10 haematological and 2 biochemical
parameters from 1,070 and 423 community children without illness prior to
experimental vaccine administration. Statistical analysis followed Clinical and
Laboratory Standards Institute EP28-A3c guidelines. 95% reference ranges and
their respective 90% confidence intervals were determined using non-parametric
methods. Findings were compared with published ranges from Tanzania, Europe and
The United States. We determined the reference ranges within the following age
partitions: 4 weeks to <6 months, 6 months to less than <12 months, and 12 months
to 17 months for the haematological parameters; and 4 weeks to 17 months for the
biochemical parameters. There were no gender differences for all haematological
and biochemical parameters in all age groups. Hb, MCV and platelets 95% reference
ranges in infants largely overlapped with those from United States or Europe,
except for the lower limit for Hb, Hct and platelets (lower); and upper limit for
platelets (higher) and haematocrit(lower). Community norms for common
haematological and biochemical parameters differ from developed countries. This
reaffirms the need in clinical trials for locally derived reference values to
detect deviation from what is usual in typical children in low and middle income
countries.
PMID- 28493931
TI - Asymptomatic carotid artery stenosis and retinal nerve fiber layer thickness. A
community-based, observational study.
AB - PURPOSE: To examine whether an abnormally thin retinal nerve fiber layer (RNFL)
is associated with cerebrovascular insufficiency. DESIGN: Community-based study.
METHODS: The Asymptomatic Polyvascular Abnormalities in Community Study included
Chinese aged 40+ years and without histories of cerebrovascular incidents or
coronary heart disease. Using transcranial Doppler and carotid duplex ultrasound
examination, we assessed presence and degree of an intracranial arterial stenosis
(ICAS) and extracranial carotid arterial stenosis (ECAS) and we measured the RNFL
thickness by spectral-domain optical coherence tomography. RESULTS: The study
included 3,376 participants with a mean age of 54.3+/-10.3 years. Thinner RNFL
was significantly correlated with a higher prevalence of ECAS (P = 0.035;
standardized regression coefficient beta:-0.04; non-standardized regression
coefficient B:-0.99; 95% confidence intervals(CI):-1.90,-0.07), after adjusting
for age (P<0.001;beta:-0.25;B:-0.26;95%CI:-0.30,-0.22), gender (P = 0.001;beta:
0.07;B:-1.36;95%CI:-2.14,-0.58) and blood concentration of low-density
lipoproteins (P = 0.03;beta:0.04;B:0.52;95%CI:0.05,0.98). In a reverse manner,
prevalence of ECAS was associated with a thinner RNFL thickness (P = 0.007; odds
ratio (OR):0.99; 95%CI:0.98,0.99) after adjusting for older age
(P<0.001;OR:1.06;95%CI:10.05,10.7), higher prevalence of ICAS (P =
0.01;OR:1.34;95%CI:1.07,1.69) and higher prevalence of carotid artery plaques
(P<0.001;OR:9.18;95%CI:6.93,12.2), and higher blood concentration of total
cholesterol (P = 0.03;OR:1.12;95%CI:1.01,1.23). In univariate analysis, an
increasing degree of ECAS was significantly correlated with a thinner RNFL.
CONCLUSIONS: Higher prevalence and degree of ECAS were correlated with thinner
RNFL and vice versa. Patients with abnormally thin RNFL without ocular disease
may undergo carotid artery examination to detect asymptomatic carotid artery
stenosis. Examination of the RNFL is useful for the diagnosis of cerebrovascular
disease.
PMID- 28493932
TI - Safety and tolerability of high-dose ulinastatin after 2-hour intravenous
infusion in adult healthy Chinese volunteers: A randomized, double-blind, placebo
controlled, ascending-dose study.
AB - Ulinastatin, is a broad-spectrum protease inhibitor purified from human urine,
inhibits endogenous proteases such as trypsin, alpha-chymotrypsin, hyaluronidase,
and plasmin. It is widely being used at increasingly higher doses for the
treatment of acute or chronic pancreatitis, severe infection, and acute organ
failure. We aimed to evaluate the safety and tolerability of high-dose
ulinastatin in healthy volunteers in our single center, randomized, double-blind,
placebo-controlled, single-dose escalation study. Fifty-one healthy Chinese
subjects were enrolled in 9 dose cohorts (3*105 U, 6*105 U, 12*105 U, 20*105 U,
30*105 U, 45*105 U, 60*105 U, 70*105 U, or 80*105 U of ulinastatin) and
randomized to UTI or matching placebo (n = 1). Each dose cohort was composed of 3
7 subjects. All subjects were required to have 2 h of intravenous infusion.
Safety and tolerability were assessed throughout the study via monitoring of
vital signs, physical examinations, clinical laboratory tests, 12-lead
electrocardiograms, and interviews with the subjects about adverse events. Fifty
one subjects (35 men and 16 women) completed the study. A total of 13 AEs were
reported by 10 subjects: 11 adverse events in the ulinastatin groups and 2
adverse events in the placebo group. Twelve of the adverse events were possibly
related to the study drug. The most common drug-related adverse events included
dizziness, pain at injection site, and a decrease in white blood cell count. All
adverse events were of mild severity; none were serious. In conclusion, 2 hours
of intravenous infusion of ulinastatin (3*105 to 80*105 U) was well tolerated by
healthy Chinese subjects.
PMID- 28493933
TI - Direct estrogen receptor (ER) / HER family crosstalk mediating sensitivity to
lumretuzumab and pertuzumab in ER+ breast cancer.
AB - Bidirectional cross talk between members of the human epidermal growth factor
family of receptors (HER) and the estrogen receptor (ER) is believed to underlie
resistance mechanisms that develop in response to treatment with anti-HER agents
and endocrine therapy. We investigated the interaction between HER2, HER3 and the
ER in vitro using human embryonic kidney cells transfected with human HER2, HER3,
and ERalpha. We also investigated the additive efficacy of combination regimens
consisting of anti-HER3 (lumretuzumab), anti-HER2 (pertuzumab), and endocrine
(fulvestrant) therapy in vivo. Our data show that both HER2 and HER3 can directly
complex with the ER and can mediate phosphorylation of the ER. Phosphorylation of
the ER was only observed in cells that expressed both HER2 and ERalpha or in
heregulin-stimulated cells that expressed both HER3 and ERalpha. Using a mouse
xenograft model of ER+/HER2-low (HER2 immunohistochemistry 1+ or 2+ without gene
amplification) human breast cancer we show that the combination of lumretuzumab
and pertuzumab is highly efficacious and induces long-lasting tumor regression in
vivo and adding endocrine therapy (fulvestrant) to this combination further
improved efficacy. In addition, a prolonged clinical response was observed with
the combination of lumretuzumab and pertuzumab in a patient with ER+/HER2-low
breast cancer who had failed endocrine therapy. These preclinical data confirm
that direct cross talk exists between HER2/HER3 and ER which may explain the
resistance mechanisms to endocrine therapy and monoclonal antibodies that target
HER2 and HER3. Our data also indicate that the triplet of anti-HER2, anti-HER3,
and endocrine therapy might be an efficacious combination for treating patients
with ER+/HER2-low breast cancer, which is an area of significant unmet medical
need.
PMID- 28493934
TI - Taking stock of the social determinants of health: A scoping review.
AB - BACKGROUND: In recent decades, the social determinants of health (SDOH) has
gained increasing prominence as a foundational concept for population and public
health in academic literature and policy documents, internationally. However,
alongside its widespread dissemination, and in light of multiple conceptual
models, lists, and frameworks, some dilution and confusion is apparent. This
scoping review represents an attempt to take stock of SDOH literature in the
context of contemporary population and public health. METHODS: We conducted a
scoping review to synthesize and map SDOH literature, informed by the methods of
Arksey and O'Malley (2005). We searched 5 academic and 3 grey literature
databases for "social determinants of health" and "population health" or "public
health" or "health promotion," published 2004-2014. We also conducted a search on
"inequity" or "inequality" or "disparity" or "social gradient" and "Canad*" to
ensure that we captured articles where this language was used to discuss the
SDOH. We included articles that discussed SDOH in depth, either explicitly or in
implicit but nuanced ways. We hand-searched reference lists to further identify
relevant articles. FINDINGS: Our synthesis of 108 articles showed wide variation
by study setting, target audience, and geographic scope, with most articles
published in an academic setting, by Canadian authors, for policy-maker
audiences. SDOH were communicated by authors as a list, model, or story; each
with strengths and weaknesses. Thematic analysis identified one theme: health
equity as an overarching and binding concept to the SDOH. Health equity was
understood in different ways with implications for action on the SDOH.
CONCLUSIONS: Among the vast SDOH literature, there is a need to identify and
clearly articulate the essence and implications of the SDOH concept. We recommend
that authors be intentional in their efforts to present and discuss SDOH to
ensure that they speak to its foundational concept of health equity.
PMID- 28493935
TI - Reproductive effort affects oxidative status and stress in an Antarctic penguin
species: An experimental study.
AB - The oxidative cost of reproduction has been a matter of debate in recent years
presumably because of the lack of proper experimental studies. Based on the
hypothesis that different brood sizes produce differential reproductive costs, an
experimental manipulation during breeding of Adelie penguins was conducted at
Hope Bay, Antarctica, to study oxidative status and stress. We predict that a
lower reproductive effort should be positively related to low oxidative and
physiological stress. We randomly assigned nests with two chicks to a control
reproductive effort group (CRE), and by removing one chick from some nests with
two chicks, formed a second, low reproductive effort group (LRE). We examined how
oxidative status in blood plasma (reactive oxygen metabolites, ROMs, and total
antioxidant capacity, OXY) and stress (heterophil/lymphocyte ratio, H/L)
responded to a lower production of offspring total biomass. Our nest manipulation
showed significant differences in offspring total biomass, which was lower in the
LRE group. As predicted, the LRE group had higher antioxidant capacity than
individuals in the CRE group. We have also found, although marginally
significant, interactions between sex and treatment in the three variables
analysed. Females had higher OXY, lower ROMs and lower H/L ratio when rearing one
chick, whereas males did so when rearing two except for OXY which was high
regardless of treatment. Moreover, there was a significant negative correlation
between the H/L ratio and OXY in females. Finally, we have found a negative and
significant relationship between the duration of the experiment and OXY and ROMs
and positive with H/L ratio which suggests that indeed breeding penguins are
paying an effort in physiological terms in relation to the duration of the chick
rearing. In conclusion, a reduction of the reproductive effort decreased
oxidative stress in this long-lived bird meaning that a link exists between
breeding effort and oxidative stress. However, our findings suggest different sex
strategies which results in opposite physiological responses presumably depending
on different life-history strategies in males and females.
PMID- 28493936
TI - Serum folate concentration and the incidence of lung cancer.
AB - BACKGROUND: Lung cancer is a leading cause of cancer-related mortality globally.
Folate helps to maintain DNA integrity and to regulate gene expression. Serum
folate levels may affect the risk of several cancers, including lung cancer. In
this study we evaluated the association between serum folate concentration and
variations in genes involved in folate metabolism with lung cancer incidence in
Poland. METHODS: The study included 366 lung cancer patients and 366 control
subjects. We measured serum folate concentration and genotyped six variants in
MTHFR, MTR and MTRR genes. The odds ratios of being diagnosed with lung cancer
were calculated using conditional univariable and multivariable logistic
regression with respect to folate level and genotypes. RESULTS: The mean serum
folate level was lower in lung cancer cases than in control group (20.07 nmol/l
vs. 22.52 nmol/l, p = 0.002). The odds ratio for lung cancer declined with
increasing serum content of the folate. The folate concentration of >25.71 nmol/l
(IVth quartile) in comparison to <15.92 nmol/l (Ist quartile) was associated with
an odds ratio of 0.61 (95%CI 0.40-0.95, p = 0.03). The analysis of variations in
MTHFR, MTR and MTRR genes did not reveal any significant difference between lung
cancer cases and controls in univariable and multivariable analyses. CONCLUSION:
In this case-control study, lower serum folate concentrations were associated
with a higher risk of lung cancer diagnosis. Although previous findings have been
somewhat mixed, our results add to the evidence that circulating folate levels
may be an indicator of lung cancer risk.
PMID- 28493937
TI - Action of tyrosinase on alpha and beta-arbutin: A kinetic study.
AB - The known derivatives from hydroquinone, alpha and beta-arbutin, are used as
depigmenting agents. In this work, we demonstrate that the oxy form of tyrosinase
(oxytyrosinase) hydroxylates alpha and beta-arbutin in ortho position of the
phenolic hydroxyl group, giving rise to a complex formed by met-tyrosinase with
the hydroxylated alpha or beta-arbutin. This complex could evolve in two ways: by
oxidizing the originated o-diphenol to o-quinone and deoxy-tyrosinase, or by
delivering the o-diphenol and met-tyrosinase to the medium, which would produce
the self-activation of the system. Note that the quinones generated in both cases
are unstable, so the catalysis cannot be studied quantitatively. However, if 3
methyl-2-benzothiazolinone hydrazone hydrochloride hydrate is used, the o-quinone
is attacked, so that it becomes an adduct, which can be oxidized by another
molecule of o-quinone, generating o-diphenol in the medium. In this way, the
system reaches the steady state and originates a chromophore, which, in turn, has
a high absorptivity in the visible spectrum. This reaction allowed us to
characterize alpha and beta-arbutin kinetically as substrates of tyrosinase for
the first time, obtaining a Michaelis constant values of 6.5 +/- 0.58 mM and 3 +/
0.19 mM, respectively. The data agree with those from docking studies that
showed that the enzyme has a higher affinity for beta-arbutin. Moreover, the
catalytic constants obtained by the kinetic studies (catalytic constant = 4.43 +/
0.33 s-1 and 3.7 +/- 0.29 s-1 for alpha and beta-arbutin respectively) agree
with our forecast based on 13 C NMR considerations. This kinetic characterization
of alpha and beta-arbutin as substrates of tyrosinase should be taken into
account to explain possible adverse effects of these compounds.
PMID- 28493938
TI - Sleep spindle detection based on non-experts: A validation study.
AB - Accurate and efficient detection of sleep spindles is a methodological challenge.
The present study describes a method of using non-experts for manual detection of
sleep spindles. We recruited five experts and 168 non-experts to manually
identify spindles in stage N2 and stage N3 sleep data using a MATLAB interface.
Scorers classified each spindle into definite and indefinite spindle (with
weights of 1 and 0.5, respectively). First, a method of optimizing the thresholds
of the expert/non-expert group consensus according to the results of experts and
non-experts themselves is described. Using this method, we established expert and
non-expert group standards from expert and non-expert scorers, respectively, and
evaluated the performance of the non-expert group standards by compared with the
expert group standard (termed EGS). The results indicated that the highest
performance was the non-expert group standard when definite spindles were only
considered (termed nEGS-1; F1 score = 0.78 for N2; 0.68 for N3). Second, four
automatic spindle detection methods were compared with the EGS. We found that the
performance of nEGS-1 versus EGS was higher than that of the four automated
methods. Our results also showed positive correlation between the mean F1 score
of individual expert in EGS and the F1 score of nEGS-1 versus EGS across 30
segments of stage N2 data (r = 0.61, P < 0.001). Further, we found that six and
nine non-experts were needed to manually identify spindles in stages N2 and N3,
respectively, while maintaining acceptable performance of nEGS-1 versus EGS (F1
score = 0.79 for N2; 0.64 for N3). In conclusion, this study establishes a
detailed process for detection of sleep spindles by non-experts in a
crowdsourcing scheme.
PMID- 28493939
TI - Inhibition of nitric oxide production reverses diabetes-induced Kupffer cell
activation and Klebsiella pneumonia liver translocation.
AB - Klebsiella pneumoniae (KP) is the most common pathogen of pyogenic liver abscess
in East and Southeast Asia and diabetes mellitus (DM) is a major risk factor. The
effect and mechanism of diabetes on KP liver abscess was examined in
streptozotocin-induced diabetic mice and Akita mice (C57BL/6J-Ins2Akita). KP
translocation to liver and plasma alaine transaminase levels were increased and
liver clearance of KP was decreased in DM mice. Diabetic mice exhibited
overgrowth of Enterococcus as well as E.coli and decreased lactobacilli/bifidas
growth in intestine, increased intestinal iNOS protein and nitrite levels in
portal vein, and increased IL-1beta and TNF-alpha expression of Kupffer cells.
Fructooligosaccharides (FOS) or dead L. salivarius (dLac) supplementation
reversed diabetes-induced enteric dysbiosis, NO levels in portal vein, and KP
translocation to liver. L-NAME treatment decreased intestinal iNOS protein
expression as well as Kupffer cell activation and increased liver clearance of KP
in DM mice. Dead E.coli (2*108 CFU/ml) feeding for one week induced iNOS and TLR4
expression of intestine in germ-free (GF) mice. Dead bacteria feeding induced IL
1beta and TNF-alpha expression of Kupffer cells in GF mice but not in GF TLR4-/-
mice. In conclusion, balance of intestinal microflora is important for preventing
intestinal iNOS expression, Kupffer cell activation, and KP liver translocation
in diabetes. Reversal of diabetes-induced enteric dysbiosis with FOS or dead L.
salivarius decreases diabetes-induced intestinal iNOS expression and KP liver
translocation. Diabetes induces Kupffer cell activation and KP liver
translocation through enteric dysbiosis and nitric oxide production.
PMID- 28493940
TI - Monte Carlo simulation for scanning technique with scattering foil free electron
beam: A proof of concept study.
AB - This study investigated the potential of a newly proposed scattering foil free
(SFF) electron beam scanning technique for the treatment of skin cancer on the
irregular patient surfaces using Monte Carlo (MC) simulation. After benchmarking
of the MC simulations, we removed the scattering foil to generate SFF electron
beams. Cylindrical and spherical phantoms with 1 cm boluses were generated and
the target volume was defined from the surface to 5 mm depth. The SFF scanning
technique with 6 MeV electrons was simulated using those phantoms. For
comparison, volumetric modulated arc therapy (VMAT) plans were also generated
with two full arcs and 6 MV photon beams. When the scanning resolution resulted
in a larger separation between beams than the field size, the plan qualities were
worsened. In the cylindrical phantom with a radius of 10 cm, the conformity
indices, homogeneity indices and body mean doses of the SFF plans (scanning
resolution = 1 degrees ) vs. VMAT plans were 1.04 vs. 1.54, 1.10 vs. 1.12 and 5
Gy vs. 14 Gy, respectively. Those of the spherical phantom were 1.04 vs. 1.83,
1.08 vs. 1.09 and 7 Gy vs. 26 Gy, respectively. The proposed SFF plans showed
superior dose distributions compared to the VMAT plans.
PMID- 28493941
TI - Influence of three lighting regimes during ten weeks growth phase on laying
performance, plasma levels- and tissue specific gene expression- of reproductive
hormones in Pengxian yellow pullets.
AB - The study was conducted to optimize lighting schedule for pre-pubertal (12 to 22
weeks) Chinese native breed Pengxian yellow pullet. A total of 414 healthy
pullets (10 weeks), with similar body weight were randomly distributed into three
groups (n = 138) and housed in individual cages for up to 12 weeks of age in
light controlled rooms and provided normal lighting schedule (10L:14D). At 12 to
18 weeks of age, pullets were housed in three rooms, having varying lighting
schedule viz. G1 (8L: 16D), G2 (10L:14D), or G3 (12L:12D). From 19th week onwards
lighting schedule was gradually increased every week in incremental manner till
all groups started receiving 16L:8D lighting schedule. The age at first egg,
weight of first egg laid, percent peak hen day egg production, concentration of
plasma luteinizing and follicle-stimulating hormones and expression of genes
regulating synthesis or/and secretion of hypothalamic gonadotropin-releasing
hormone-I (GnRH-I), and pituitary LH-beta and FSH-beta were studied during
experimental period (12 to 43 weeks of age) of this study. The result indicated
that pullets of long day length (G3) group had higher plasma levels of FSH and LH
and also better mRNA expression that regulates synthesis or/and secretion of GnRH
I, FSH-beta, and LH-beta before egg laying. The age at first egg (151.3 days) in
pullets of G3 group receiving longer lighting hours (12L:12D) was 8.8 days less
(P<0.05) compared to pullets of G1 group, while it was 6.9 days less (P>0.05)
compared to G2. However, significantly higher (P<0.05) plasma levels of LH and
FSH in pullets of G1 as compared to pullets belonging to G3 group corresponded
with the higher (P<0.05) cumulative egg production during the experimental
period, while these attributes in G2 group didn't differ from either G1 or G3
groups. Pullets of G1 group had significantly higher levels (P<0.05) of GnRH-I,
FSH-beta, and LH-beta mRNA abundances at 43 weeks of age than other two groups
and this corresponded with the percent (hen day) peak egg production (75.38%) in
pullets in this G1 group that was attained at 32 weeks of age, while the peak
production of 71.24% was attained at 30 weeks of age in G3 group. There was no
effect of lighting schedule on body weight of pullets, recorded during
experimental period, at all occasions; belonging to three groups (G1,G2 and G3)
and receiving varying hours of photo-stimulation (P>0.05). It was inferred that
the optimum lighting schedule for Chinese native breed Pengxian yellow pullets
during 10 weeks of pre-pubertal growth period is short hours of photo-stimulation
(i.e 8L:16D).
PMID- 28493943
TI - Open lung approach versus standard protective strategies: Effects on driving
pressure and ventilatory efficiency during anesthesia - A pilot, randomized
controlled trial.
AB - BACKGROUND: Low tidal volume (VT) during anesthesia minimizes lung injury but may
be associated to a decrease in functional lung volume impairing lung mechanics
and efficiency. Lung recruitment (RM) can restore lung volume but this may
critically depend on the post-RM selected PEEP. This study was a randomized, two
parallel arm, open study whose primary outcome was to compare the effects on
driving pressure of adding a RM to low-VT ventilation, with or without an
individualized post-RM PEEP in patients without known previous lung disease
during anesthesia. METHODS: Consecutive patients scheduled for major abdominal
surgery were submitted to low-VT ventilation (6 ml.kg-1) and standard PEEP of 5
cmH2O (pre-RM, n = 36). After 30 min estabilization all patients received a RM
and were randomly allocated to either continue with the same PEEP (RM-5 group, n
= 18) or to an individualized open-lung PEEP (OL-PEEP) (Open Lung Approach, OLA
group, n = 18) defined as the level resulting in maximal Cdyn during a
decremental PEEP trial. We compared the effects on driving pressure and lung
efficiency measured by volumetric capnography. RESULTS: OL-PEEP was found at 8+/
2 cmH2O. 36 patients were included in the final analysis. When compared with pre
RM, OLA resulted in a 22% increase in compliance and a 28% decrease in driving
pressure when compared to pre-RM. These parameters did not improve in the RM-5.
The trend of the DP was significantly different between the OLA and RM-5 groups
(p = 0.002). VDalv/VTalv was significantly lower in the OLA group after the RM (p
= 0.035). CONCLUSIONS: Lung recruitment applied during low-VT ventilation
improves driving pressure and lung efficiency only when applied as an open-lung
strategy with an individualized PEEP in patients without lung diseases undergoing
major abdominal surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT02798133.
PMID- 28493942
TI - Amplifying recombination genome-wide and reshaping crossover landscapes in
Brassicas.
AB - Meiotic recombination by crossovers (COs) is tightly regulated, limiting its key
role in producing genetic diversity. However, while COs are usually restricted in
number and not homogenously distributed along chromosomes, we show here how to
disrupt these rules in Brassica species by using allotriploid hybrids (AAC, 2n =
3x = 29), resulting from the cross between the allotetraploid rapeseed (B. napus,
AACC, 2n = 4x = 38) and one of its diploid progenitors (B. rapa, AA, 2n = 2x =
20). We produced mapping populations from different genotypes of both diploid AA
and triploid AAC hybrids, used as female and/or as male. Each population revealed
nearly 3,000 COs that we studied with SNP markers well distributed along the A
genome (on average 1 SNP per 1.25 Mbp). Compared to the case of diploids,
allotriploid hybrids showed 1.7 to 3.4 times more overall COs depending on the
sex of meiosis and the genetic background. Most surprisingly, we found that such
a rise was always associated with (i) dramatic changes in the shape of
recombination landscapes and (ii) a strong decrease of CO interference. Hybrids
carrying an additional C genome exhibited COs all along the A chromosomes, even
in the vicinity of centromeres that are deprived of COs in diploids as well as in
most studied species. Moreover, in male allotriploid hybrids we found that Class
I COs are mostly responsible for the changes of CO rates, landscapes and
interference. These results offer the opportunity for geneticists and plant
breeders to dramatically enhance the generation of diversity in Brassica species
by disrupting the linkage drag coming from limits on number and distribution of
COs.
PMID- 28493944
TI - A decade of viral mutations and associated drug resistance in a population of HIV
1+ Puerto Ricans: 2002-2011.
AB - Puerto Rico has one of the highest rates of HIV/AIDS seen for any US state or
territory, and antiretroviral therapy has been a mainstay of efforts to mitigate
the HIV/AIDS public health burden on the island. We studied the evolutionary
dynamics of HIV-1 mutation and antiretroviral drug resistance in Puerto Rico by
monitoring the population frequency of resistance-associated mutations from 2002
to 2011. Whole blood samples from 4,475 patients were analyzed using the TRUGENE
HIV-1 Genotyping Kit and OpenGene DNA Sequencing System in the Immunoretrovirus
Research Laboratory at Universidad Central del Caribe. Results show that 64.0% of
female and 62.9% of male patients had HIV-1 mutations that confer resistance to
at least one antiretroviral medication. L63P and M184V were the dominant
mutations observed for the protease (PRO) and reverse transcriptase (RT) encoding
genes, respectively. Specific resistance mutations, along with their associated
drug resistance profiles, can be seen to form temporal clusters that reveal a
steadily changing landscape of resistance trends over time. Both women and men
showed resistance mutations for an average of 4.8 drugs over the 10-year period,
further underscoring the strong selective pressure exerted by antiretrovirals
along with the rapid adaptive response of HIV. Nevertheless, both female and male
patients showed a precipitous decrease for overall drug resistance, and for PRO
mutations in particular, over the entire course of the study, with the most rapid
decrease in frequency seen after 2006. The reduced HIV-1 mutation and drug
resistance trends that we observed are consistent with previous reports from
multi-year studies conducted around the world. Reduced resistance can be
attributed to the use of more efficacious antiretroviral drug therapy, including
the introduction of multi-drug combination therapies, which limited the ability
of the virus to mount rapid adaptive responses to antiretroviral selection
pressure.
PMID- 28493945
TI - Ebola virus RNA detection on fomites in close proximity to confirmed Ebola
patients; N'Zerekore, Guinea, 2015.
AB - OBJECTIVE: Health care workers (HCWs) in contact with patients with Ebola virus
disease (EVD) are exposed to a risk of viral contamination. Fomites contaminated
with the patient's blood or body fluids represents this risk. Our study aims to
detect Ebola virus (EBOV) RNA within the high- and low-risk areas of an Ebola
treatment unit (ETU) located in inland Guinea during the 2014-2015 West African
Ebola epidemics. For samples from patients' immediate vicinity, we aim to seek an
association between viral RNA detectability and level of plasma viral load of
patients (intermediate to high, or very high). METHODS: Swabbing was performed on
immediate vicinity of Ebola patients, on surfaces of an ETU, and on personal
protective equipment (PPE) of HCWs after patient care and prior to doffing. All
samples were assessed by quantitative reverse-transcribed PCR (RT-qPCR). RESULTS:
32% (22/68) of swabs from high-risk areas were tested positive for EBOV RNA,
including 42% (18/43) from patients' immediate vicinity, and 16% (4/25) from HCWs
PPE. None of specimens from low-risk areas were tested positive (0/19). Swabs
were much more often viral RNA positive in the vicinity of patients with a very
high plasma viral load (OR 6.7, 95% CI [1.7-23.4]). CONCLUSION: Our findings show
the persistence of EBOV RNA in the environment of Ebola patients and of HCWs, in
a Guinean ETU, despite strict infection prevention and control measures. This
detection raises the possibility that patients' environment could be a potential
source of contamination with the virus.
PMID- 28493946
TI - Functional decline in nursing home residents: A prognostic study.
AB - AIM: To verify the probability of maintaining functional capacity in basic
activities of daily living and identify the prognostic factors of functional
decline in institutionalized older adults. METHODS: A longitudinal study is
presented herein, with 5 waves every 6 months, throughout 2 years (2013-2015),
conducted with individuals >=60 years old in 10 nursing homes in the city of
Natal-RN (Brazil). Functional capacity was assessed by the items 'eating',
'personal hygiene', 'dressing', 'bathing', 'transferring', 'toileting' and
'walking', through a 5-item Likert scale. Sociodemographic, institution-related
and health-related variables were considered to establish the baseline. Time
dependent variables included continence decline, cognitive decline, increase in
the number of medication, and incidences of falls, hospitalizations and
fractures. The actuarial method, the log-rank test and Cox's regression were
applied as statistical methods. RESULTS: The cumulative probability of functional
maintenance was 78.2% (CI 95%: 72.8-82.7%), 65.1% (CI 95%: 58.9-70.5%), 53.5% (CI
95%: 47.2-59.5%) and 44.0% (CI 95%: 37.7-50.2%) at 6, 12, 18 and 24 months,
respectively. Predicting factors for functional decline were: severe cognitive
impairment (HR = 1.96; p = 0.001), continence decline (HR = 1.85; p = 0.002) and
incidence of hospitalizations (HR = 1.62; p = 0.020), adjusted by the incidence
of depression, age, education level, presence of chronic diseases and low weight.
CONCLUSIONS: The cumulative probability of maintaining functional capacity in
institutionalized older adults was only 44% at the 2-year follow-up. Prognostic
factors for functional decline included severe cognitive impairment, continence
decline and incidence of hospitalizations.
PMID- 28493948
TI - Gender bias in clinical case reports: A cross-sectional study of the "big five"
medical journals.
AB - BACKGROUND: Gender bias in medical journals can affect the science and the
benefit to patients. It has never been investigated in clinical case reports. The
oversight is important because of the role clinical case reports play in
hypothesis generation and medical education. We investigated contemporary gender
bias in case reports for the highest ranked journals in general and internal
medicine. METHODS: PubMed case reports data from 2011 to 2016 were extracted for
the Annals of Internal Medicine, British Medical Journal, the Journal of the
American Medical Association, The Lancet, and New England Journal of Medicine.
The gender of the patients were identified and a text analysis of the Medical
Subject Headings conducted. RESULTS: A total of 2,742 case reports were
downloaded and 2,582 (95.6%) reports contributed to the final analysis. A pooled
analysis showed a statistically significant gender bias against female case
reports (0.45; 95%CI: 0.43-0.47). The Annals of Internal Medicine was the only
journal with a point estimate (non significant) in the direction of a bias
against male patients. The text analysis identified no substantive difference in
the focus of the case reports and no obvious explanation for the bias.
CONCLUSION: Gender bias, previously identified in clinical research and in
clinical authorship, extends into the patients presented in clinical case
reports. Whether it is driven by authors or editors is not clear, but it likely
contributes to and supports an overall male bias of clinical medicine.
PMID- 28493947
TI - Post-translational modifications of FDA-approved plasma biomarkers in
glioblastoma samples.
AB - Liquid chromatography-tandem mass spectrometry was used to analyze plasma
proteins of volunteers (control) and patients with glioblastoma multiform (GBM).
A database search was pre-set with a variable post-translational modification
(PTM): phosphorylation, acetylation or ubiquitination. There were no significant
differences between the control and the GBM groups regarding the number of
protein identifications, sequence coverage or number of PTMs. However, in GBM
plasma, we unambiguously observed a decreased fraction in post-translationally
modified peptides identified with high quality. The disease-specific PTM patterns
were extracted and mapped to the set of FDA-approved plasma protein markers.
Decreases of 46% and 24% in the number of acetylated and ubiquitinated peptides,
respectively, were observed in the GBM samples. Significance of capturing disease
associated patterns of protein modifications was envisaged.
PMID- 28493949
TI - Prediction of pancreatic fistula after pancreatoduodenectomy by preoperative
dynamic CT and fecal elastase-1 levels.
AB - OBJECTIVE: To validate preoperative dynamic CT and fecal elastase-1 level in
predicting the development of pancreatic fistulae after pancreatoduodenectomy.
MATERIALS AND METHODS: For 146 consecutive patients, CT attenuation values of the
nontumorous pancreatic parenchyma were retrospectively measured on precontrast,
arterial and equilibrium phase images for calculation of enhancement ratios. CT
enhancement ratios and preoperative fecal elastase-1 levels were correlated with
the development of pancreatic fistulae using independent t-test, logistic
regression models, ROC analysis, Youden method and tree analysis. RESULTS: The
mean value of enhancement ratio on equilibrium phase was significantly higher (p
= 0.001) in the patients without pancreatic fistula (n = 107; 2.26+/-3.63) than
in the patients with pancreatic fistula (n = 39; 1.04+/-0.51); in the logistic
regression analyses, it was significant predictor for the development of
pancreatic fistulae (odds ratio = 0.243, p = 0.002). The mean preoperative fecal
elastase-1 levels were higher (odds ratio = 1.003, p = 0.034) in the pancreatic
fistula patients than other patients, but there were no significant differences
in the areas under the curve between the prediction values of CT enhancement
ratios and fecal elastase-1 combined and those of CT enhancement ratios alone (P
= 0.897, p = 0.917) on ROC curve analysis. Tree analysis revealed that the CT
enhancement ratio was more powerful predictor of pancreatic fistula than fecal
elastase-1 levels. CONCLUSION: The preoperative CT enhancement ratio of pancreas
acquired at equilibrium phase regardless of combination with fecal elastase-1
levels might be a useful predictor of the risk of developing a pancreatic fistula
following pancreatoduodenectomy.
PMID- 28493950
TI - SAS profile correlations reveal SAS hierarchical nature and information content.
AB - In structural biology, Small-Angle Scattering experiments (SAS) are unique,
because although they provide low resolution data, they can be performed in
closer-to-native conditions than those arising in X-Ray crystallography. A number
of questions on SAS, however, remain unsolved, particularly in the light of
modelling ensembles of conformers in solution. In this article, we study the
ensemble average and covariance of SAS profiles analytically. Using this ensemble
covariance, we demonstrate the hierarchical nature of SAS profiles. Furthermore,
we show that the information content is not uniform and reaches its maximum in
the intermediate q range. The arguments are generalized using microsecond-scale
molecular dynamics trajectories of the lysozyme and on an ensemble of the
intrinsically disordered protein p15PAF. We show that for highly flexible
systems, the SAS profile is a representation of the ensemble of conformers in
solution, and not that of one conformer in particular.
PMID- 28493951
TI - Properties of biochar derived from wood and high-nutrient biomasses with the aim
of agronomic and environmental benefits.
AB - Biochar production and use are part of the modern agenda to recycle wastes, and
to retain nutrients, pollutants, and heavy metals in the soil and to offset some
greenhouse gas emissions. Biochars from wood (eucalyptus sawdust, pine bark),
sugarcane bagasse, and substances rich in nutrients (coffee husk, chicken manure)
produced at 350, 450 and 750 degrees C were characterized to identify agronomic
and environmental benefits, which may enhance soil quality. Biochars derived from
wood and sugarcane have greater potential for improving C storage in tropical
soils due to a higher aromatic character, high C concentration, low H/C ratio,
and FTIR spectra features as compared to nutrient-rich biochars. The high ash
content associated with alkaline chemical species such as KHCO3 and CaCO3,
verified by XRD analysis, made chicken manure and coffee husk biochars potential
liming agents for remediating acidic soils. High Ca and K contents in chicken
manure and coffee husk biomass can significantly replace conventional sources of
K (mostly imported in Brazil) and Ca, suggesting a high agronomic value for these
biochars. High-ash biochars, such as chicken manure and coffee husk, produced at
low-temperatures (350 and 450 degrees C) exhibited high CEC values, which can be
considered as a potential applicable material to increase nutrient retention in
soil. Therefore, the agronomic value of the biochars in this study is
predominantly regulated by the nutrient richness of the biomass, but an increase
in pyrolysis temperature to 750 degrees C can strongly decrease the adsorptive
capacities of chicken manure and coffee husk biochars. A diagram of the agronomic
potential and environmental benefits is presented, along with some guidelines to
relate biochar properties with potential agronomic and environmental uses. Based
on biochar properties, research needs are identified and directions for future
trials are delineated.
PMID- 28493952
TI - A mutation in the CACNA1C gene leads to early repolarization syndrome with
incomplete penetrance: A Chinese family study.
AB - BACKGROUND: Early repolarization syndrome (ERS) may be a near-Mendelian or an
oligogenic disease; however, no direct evidence has been provided to support this
theory. METHODS AND RESULTS: We described a large Chinese family with nocturnal
sudden cardiac death induced by ERS in most of the young male adults. One
missense mutation (p.Q1916R) was found in the major subunit of the L-type calcium
channel gene CACNA1C by the direct sequencing of candidate genes. A concomitant
gain-of-function variant in the sodium channel gene SCN5A (p.R1193Q) was found to
rescue the phenotype of the female CACNA1C-Q1916R mutation carriers, which led to
the incomplete penetrance. The functional studies, via the exogenous expression
approach, revealed that the CACNA1C-Q1916R mutation led to a decreasing L-type
calcium current and the protein expression defect. The decreased calcium current
produced by the mutant channel was improved by isoproterenol but exacerbated by
testosterone. The effects of CACNA1C-Q1916R mutation and testosterone on cellular
electrophysiology were further confirmed by the human ventricular action
potential simulation. CONCLUSIONS: Our results demonstrated that the loss-of
function CACNA1C-Q1916R mutation contributed to ERS-related sudden cardiac death,
and the phenotypic incomplete penetrance was modified by the SCN5A-R1193Q variant
and sex. These findings suggest that phenotypes of ERS are modified by multiple
genetic factors, which supports the theory that ERS may be an oligogenic disease.
PMID- 28493953
TI - The association between vacA or cagA status and eradication outcome of
Helicobacter pylori infection: A meta-analysis.
AB - BACKGROUND: H. pylori virulence factors, especially vacA and cagA are important
in gastroduodenal disease pathogenesis and affect cure rates. This meta-analysis
aimed to clarify the association between vacA or cagA status and eradication
outcome of H. pylori infection. METHODS: A literature search was performed using
electronic databases to identify studies. Twenty-six prospective studies were
determined eligible. Meta-analytical techniques were conducted to calculate
eradication rates and pooled relative ratios (RR). RESULTS: The eradication rate
was greater approximately 10% in vacA s1 compared with vacA s2 infected patients,
and the pooled RR was 1.164 (95%CI: 1.040-1.303, P = 0.008). A significant
association existed between vacA s1 and higher eradication rates in Europe (RR:
1.203, 95%CI: 1.003-1.442, P = 0.046) and Asia (RR: 1.187, 95%CI: 1.028-1.371, P
= 0.020), in triple therapy patients (RR: 1.175, 95%CI: 1.012-1.365, P = 0.035).
Eradication rates were similar for vacA m1 and m2 genotypes (RR: 0.981, 95%CI:
0.891-1.080, P = 0.690), whereas they were higher by approximately 8% in cagA
positive compared with cagA-negative infected patients, with a pooled RR of 1.094
(95%CI: 1.025-1.168, P = 0.007). A significant association existed between cagA
positive and increased eradication rates in Europe (RR: 1.138, 95%CI: 1.000
1.295, P = 0.049) and Asia (RR: 1.118, 95%CI: 1.051-1.190, P<0.001), in using PCR
(RR: 1.232, 95%CI: 1.142-1.329, P<0.001) and protein chips (RR: 1.200, 95%CI:
1.060-1.359, P = 0.004), in triple therapy patients (RR: 1.090, 95%CI: 1.006
1.181, P = 0.034). CONCLUSIONS: Evidence indicates that infection with vacA s1,
cagA-positive strains, but not vacA s2, cagA-negative, is more conducive to H.
pylori eradication.
PMID- 28493954
TI - A model for predicting Xanthomonas arboricola pv. pruni growth as a function of
temperature.
AB - A two-step modeling approach was used for predicting the effect of temperature on
the growth of Xanthomonas arboricola pv. pruni, causal agent of bacterial spot
disease of stone fruit. The in vitro growth of seven strains was monitored at
temperatures from 5 to 35 degrees C with a Bioscreen C system, and a calibrating
equation was generated for converting optical densities to viable counts. In
primary modeling, Baranyi, Buchanan, and modified Gompertz equations were fitted
to viable count growth curves over the entire temperature range. The modified
Gompertz model showed the best fit to the data, and it was selected to estimate
the bacterial growth parameters at each temperature. Secondary modeling of
maximum specific growth rate as a function of temperature was performed by using
the Ratkowsky model and its variations. The modified Ratkowsky model showed the
best goodness of fit to maximum specific growth rate estimates, and it was
validated successfully for the seven strains at four additional temperatures. The
model generated in this work will be used for predicting temperature-based
Xanthomonas arboricola pv. pruni growth rate and derived potential daily
doublings, and included as the inoculum potential component of a bacterial spot
of stone fruit disease forecaster.
PMID- 28493956
TI - Socio-demographic predictors and average annual rates of caesarean section in
Bangladesh between 2004 and 2014.
AB - BACKGROUND: Globally the rates of caesarean section (CS) have steadily increased
in recent decades. This rise is not fully accounted for by increases in clinical
factors which indicate the need for CS. We investigated the socio-demographic
predictors of CS and the average annual rates of CS in Bangladesh between 2004
and 2014. METHODS: Data were derived from four waves of nationally representative
Bangladesh Demographic and Health Survey (BDHS) conducted between 2004 and 2014.
Rate of change analysis was used to calculate the average annual rate of increase
in CS from 2004 to 2014, by socio-demographic categories. Multi-level logistic
regression was used to identify the socio-demographic predictors of CS in a cross
sectional analysis of the 2014 BDHS data. RESULT: CS rates increased from 3.5% in
2004 to 23% in 2014. The average annual rate of increase in CS was higher among
women of advanced maternal age (>=35 years), urban areas, and relatively high
socio-economic status; with higher education, and who regularly accessed
antenatal services. The multi-level logistic regression model indicated that
lower (<=19) and advanced maternal age (>=35), urban location, relatively high
socio-economic status, higher education, birth of few children (<=2), antenatal
healthcare visits, overweight or obese were the key factors associated with
increased utilization of CS. Underweight was a protective factor for CS.
CONCLUSION: The use of CS has increased considerably in Bangladesh over the
survey years. This rising trend and the risk of having CS vary significantly
across regions and socio-economic status. Very high use of CS among women of
relatively high socio-economic status and substantial urban-rural difference call
for public awareness and practice guideline enforcement aimed at optimizing the
use of CS.
PMID- 28493955
TI - Molecular diversity analysis, drought related marker-traits association mapping
and discovery of excellent alleles for 100-day old plants by EST-SSRs in cassava
germplasms (Manihot esculenta Cranz).
AB - Cassava is the third largest food crop of the world and has strong ability of
drought tolerance. In order to evaluate the molecular diversity and to discover
novel alleles for drought tolerance in cassava germplasms, we examined a total of
107 abiotic stress related expressed sequence tags-simple sequence repeat (EST
SSR) markers in 134 cassava genotypes coming from planting regions worldwide and
performed drought related marker-traits association mapping. As results, we
successfully amplified 98 of 107 markers in 97 polymorphic loci and 279 alleles,
with 2.87 alleles per locus, gene diversity of 0.48 and polymorphic information
content (PIC) of 0.41 on average. The genetic coefficient between every two lines
was 0.37 on average, ranging from 0.21 to 0.82. According to our population
structure analysis, these samples could be divided into three sub-populations
showing obvious gene flow between them. We also performed water stress
experiments using 100-day old cassava plants in two years and calculated the
drought tolerance coefficients (DTCs) and used them as phenotypes for marker
trait association mapping. We found that 53 markers were significantly associated
with these drought-related traits, with a contribution rate for trait variation
of 8.60% on average, ranging between 2.66 and 28.09%. Twenty-four of these 53
associated genes showed differential transcription or protein levels which were
confirmed by qRT-PCR under drought stress when compared to the control conditions
in cassava. Twelve of twenty-four genes were the same differential expression
patterns in omics data and results of qRT-PCR. Out of 33 marker-traits
combinations on 24 loci, 34 were positive and 53 negative alleles according to
their phenotypic effects and we also obtained the typical materials which carried
these elite alleles. We also found 23 positive average allele effects while 10
loci were negative according to their allele effects (AAEs). Our results on
molecular diversity, locus association and differential expression under drought
can prove beneficial to select excellent materials through marker assisted
selection and for functional genes research in the future.
PMID- 28493958
TI - Evolutionary transition towards permanent chloroplasts? - Division of
kleptochloroplasts in starved cells of two species of Dinophysis (Dinophyceae).
AB - Species within the marine toxic dinoflagellate genus Dinophysis are phagotrophic
organisms that exploit chloroplasts (kleptochloroplasts) from other protists to
perform photosynthesis. Dinophysis spp. acquire the kleptochloroplasts from the
ciliate Mesodinium rubrum, which in turn acquires the chloroplasts from a unique
clade of cryptophytes. Dinophysis spp. digest the prey nuclei and all other cell
organelles upon ingestion (except the kleptochloroplasts) and they are therefore
believed to constantly acquire new chloroplasts as the populations grow. Previous
studies have, however, indicated that Dinophysis can keep the kleptochloroplasts
active during long term starvation and are able to produce photosynthetic
pigments when exposed to prey starvation. This indicates a considerable control
over the kleptochloroplasts and the ability of Dinophysis to replicate its
kleptochloroplasts was therefore re-investigated in detail in this study. The
kleptochloroplasts of Dinophysis acuta and Dinophysis acuminata were analyzed
using confocal microscopy and 3D bioimaging software during long term starvation
experiments. The cell concentrations were monitored to confirm cell divisions and
samples were withdrawn each time a doubling had occurred. The results show direct
evidence of kleptochloroplastidic division and that the decreases in total
kleptochloroplast volume, number of kleptochloroplasts and number of
kleptochloroplast centers were not caused by dilution due to cell divisions. This
is the first report of division of kleptochloroplasts in any protist without the
associated prey nuclei. This indicates that Dinophysis spp. may be in a
transitional phase towards possessing permanent chloroplasts, which thereby
potentially makes it a key organism to understand the evolution of phototrophic
protists.
PMID- 28493957
TI - Ezrin interacts with S100A4 via both its N- and C-terminal domains.
AB - Ezrin belongs to the ERM (ezrin, radixin, moesin) protein family that has a role
in cell morphology changes, adhesion and migration as an organizer of the
cortical cytoskeleton by linking actin filaments to the apical membrane of
epithelial cells. It is highly expressed in a variety of human cancers and
promotes metastasis. Members of the Ca2+-binding EF-hand containing S100 proteins
have similar pathological properties; they are overexpressed in cancer cells and
involved in metastatic processes. In this study, using tryptophan fluorescence
and stopped-flow kinetics, we show that S100A4 binds to the N-terminal ERM domain
(N-ERMAD) of ezrin with a micromolar affinity. The binding involves the F2 lobe
of the N-ERMAD and follows an induced fit kinetic mechanism. Interestingly,
S100A4 binds also to the unstructured C-terminal actin binding domain (C-ERMAD)
with similar affinity. Using NMR spectroscopy, we characterized the complex of
S100A4 with the C-ERMAD and demonstrate that no ternary complex is simultaneously
formed with the two ezrin domains. Furthermore, we show that S100A4 co-localizes
with ezrin in HEK-293T cells. However, S100A4 very weakly binds to full-length
ezrin in vitro indicating that the interaction of S100A4 with ezrin requires
other regulatory events such as protein phosphorylation and/or membrane binding,
shifting the conformational equilibrium of ezrin towards the open state. As both
proteins play an important role in promoting metastasis, the characterization of
their interaction could shed more light on the molecular events contributing to
this pathological process.
PMID- 28493959
TI - Novel genetic locus at MHC region for esophageal squamous cell carcinoma in
Chinese populations.
AB - BACKGROUND: Our previous genome-wide association study (GWAS) identified three
independent single nucleotide polymorphisms (SNPs) in human major
histocompatibility complex (MHC) region showing association with esophageal
squamous cell carcinoma (ESCC). In this study, we increased GWAS sample size on
MHC region and performed validation in an independent ESCC cases and normal
controls with aim to find additional loci at MHC region showing association with
an increased risk to ESCC. METHODS: The 1,077 ESCC cases and 1,733 controls were
genotyped using Illumina Human 610-Quad Bead Chip, and 451 cases and 374 controls
were genotyped using Illumina Human 660W-Quad Bead Chip. After quality control,
the selected SNPs were replicated by TaqMan genotyping assay on another 2,026
ESCC cases and 2,384 normal controls. RESULTS: By excluding low quality SNPs in
primary GWAS screening, we selected 2,533 SNPs in MHC region for association
analysis, and identified 5 SNPs with p <10-4. Further validation analysis in an
independent case-control cohort confirmed one of the 5 SNPs (rs911178) that
showed significant association with ESCC. rs911178 (PGWAS = 6.125E-04, OR = 0.644
and Preplication = 1.406E-22, OR = 0.489) was located at upstream of SCAND3.
CONCLUSION: The rs911178 (SCAND3 gene) in MHC region is significantly associated
with high risk of ESCC. This study not only reveal the potential role of MHC
region for the pathogenesis of ESCC, but also provides important clues for the
establishment of tools and methods for screening high risk population of ESCC.
PMID- 28493960
TI - Diagnostic of students' misconceptions using the Biological Concepts Instrument
(BCI): A method for conducting an educational needs assessment.
AB - Concept inventories, constructed based on an analysis of students' thinking and
their explanations of scientific situations, serve as diagnostics for identifying
misconceptions and logical inconsistencies and provide data that can help direct
curricular reforms. In the current project, we distributed the Biological
Concepts Instrument (BCI) to 17-18-year-old students attending the highest track
of the Swiss school system (Gymnasium). Students' performances on many questions
related to evolution, genetics, molecular properties and functions were diverse.
Important common misunderstandings were identified in the areas of evolutionary
processes, molecular properties and an appreciation of stochastic processes in
biological systems. Our observations provide further evidence that the BCI is
efficient in identifying specific areas where targeted instruction is required.
Based on these observations we have initiated changes at several levels to
reconsider how biological systems are presented to university biology studies
with the goal of improving student's foundational understanding.
PMID- 28493962
TI - Genetic diversity and population structure of Chinese natural bermudagrass
[Cynodon dactylon (L.) Pers.] germplasm based on SRAP markers.
AB - Bermudagrass [Cynodon dactylon (L.) Pers.], an important turfgrass used in public
parks, home lawns, golf courses and sports fields, is widely distributed in
China. In the present study, sequence-related amplified polymorphism (SRAP)
markers were used to assess genetic diversity and population structure among 157
indigenous bermudagrass genotypes from 20 provinces in China. The application of
26 SRAP primer pairs produced 340 bands, of which 328 (96.58%) were polymorphic.
The polymorphic information content (PIC) ranged from 0.36 to 0.49 with a mean of
0.44. Genetic distance coefficients among accessions ranged from 0.04 to 0.61,
with an average of 0.32. The results of STRUCTURE analysis suggested that 157
bermudagrass accessions can be grouped into three subpopulations. Moreover,
according to clustering based on the unweighted pair-group method of arithmetic
averages (UPGMA), accessions were divided into three major clusters. The UPGMA
dendrogram revealed that accessions from identical or adjacent areas were
generally, but not entirely, clustered into the same cluster. Comparison of the
UPGMA dendrogram and the Bayesian STRUCTURE analysis showed general agreement
between the population subdivisions and the genetic relationships among
accessions. Principal coordinate analysis (PCoA) with SRAP markers revealed a
similar grouping of accessions to the UPGMA dendrogram and STRUCTUE analysis.
Analysis of molecular variance (AMOVA) indicated that 18% of total molecular
variance was attributed to diversity among subpopulations, while 82% of variance
was associated with differences within subpopulations. Our study represents the
most comprehensive investigation of the genetic diversity and population
structure of bermudagrass in China to date, and provides valuable information for
the germplasm collection, genetic improvement, and systematic utilization of
bermudagrass.
PMID- 28493961
TI - Aldosterone signaling regulates the over-expression of claudin-4 and -8 at the
distal nephron from type 1 diabetic rats.
AB - Hyperglycemia in diabetes alters tight junction (TJ) proteins in the kidney. We
evaluated the participation of aldosterone (ALD), and the effect of
spironolactone (SPL), a mineralocorticoid receptor antagonist, on the expressions
of claudin-2, -4, -5 and -8, and occludin in glomeruli, proximal and distal
tubules isolated from diabetic rats. Type 1 diabetes was induced in female Wistar
rats by a single tail vein injection of streptozotocin (STZ), and SPL was
administrated daily by gavage, from days 3-21. Twenty-one days after STZ
injection the rats were sacrificed. In diabetic rats, the serum ALD levels were
increased, and SPL-treatment did not have effect on these levels or in
hyperglycemia, however, proteinuria decreased in SPL-treated diabetic rats.
Glomerular damage, evaluated by nephrin and Wilm's tumor 1 (WT1) protein
expressions, and proximal tubular damage, evaluated by kidney injury molecule 1
(Kim-1) and heat shock protein 72 kDa (Hsp72) expressions, were ameliorated by
SPL. Also, SPL prevented decrement in claudin-5 in glomeruli, and claudin-2 and
occludin in proximal tubules by decreasing oxidative stress, evaluated by
superoxide anion (O2?-) production, and oxidative stress markers. In distal
tubules, SPL ameliorated increase in mRNA, protein expression, and
phosphorylation in threonine residues of claudin-4 and -8, through a serum and
glucocorticoid-induced kinase 1 (SGK1), and with-no-lysine kinase 4 (WNK4)
signaling pathway. In conclusion, this is the first study that demonstrates that
ALD modulates the expression of renal TJ proteins in diabetes, and that the
blockade of its actions with SPL, may be a promising therapeutic strategy to
prevent alterations of TJ proteins in diabetic nephropathy.
PMID- 28493963
TI - Expression in Sf9 insect cells, purification and functional reconstitution of the
human proton-coupled folate transporter (PCFT, SLC46A1).
AB - The proton-coupled folate transporter (PCFT) provides an essential uptake route
for the vitamin folic acid (B9) in mammals. In addition, it is currently of high
interest for targeting chemotherapeutic agents to tumors due to the increased
folic acid requirement of rapidly dividing tumor cells as well as the upregulated
PCFT expression in several tumors. To understand its function, determination of
its atomic structure and molecular mechanism of transport are essential goals
that require large amounts of functional PCFT. Here, we present a high-level
heterologous expression system for human PCFT using a recombinant baculovirus and
Spodoptera frugiperda (Sf9) insect cells. We demonstrate folate transport
functionality along the PCFT expression, isolation, and purification process.
Importantly, purified PCFT transports folic acid after reconstitution. We thus
succeeded in overcoming heterologous expression as a major bottleneck of PCFT
research. The availability of an overexpression system for human PCFT provides
the basis for future biochemical, biophysical and structural studies.
PMID- 28493964
TI - Non-human primate orthologues of TMPRSS2 cleave and activate the influenza virus
hemagglutinin.
AB - The cellular serine protease TMPRSS2, a member of the type II transmembrane
serine protease (TTSP) family, cleaves and activates the hemagglutinin of
influenza A viruses (FLUAV) in cell culture and is essential for spread of
diverse FLUAV in mice. Non-human primates (NHP), in particular rhesus and
cynomolgus macaques, serve as animal models for influenza and experimental FLUAV
infection of common marmosets has recently also been reported. However, it is
currently unknown whether the NHP orthologues of human TMPRSS2 cleave and
activate FLUAV hemagglutinin and contribute to viral spread in respiratory
tissue. Here, we cloned and functionally analyzed the macaque and marmoset
orthologues of human TMPRSS2. In addition, we analyzed the macaque orthologues of
human TMPRSS4 and HAT, which also belong to the TTSP family. We found that all
NHP orthologues of human TMPRSS2, TMPRSS4 and HAT cleave and activate HA upon
directed expression and provide evidence that endogenous TMPRSS2 is expressed in
the respiratory epithelium of rhesus macaques. Finally, we demonstrate that a
serine protease inhibitor active against TMPRSS2 suppresses FLUAV spread in
precision-cut lung slices of human, macaque and marmoset origin. These results
indicate that FLUAV depends on serine protease activity for spread in diverse NHP
and in humans. Moreover, our findings suggest that macaques and marmosets may
serve as models to study FLUAV activation by TMPRSS2 in human patients.
PMID- 28493965
TI - Assessing the greenhouse gas emissions of Brazilian soybean biodiesel production.
AB - Soybean biodiesel (B100) has been playing an important role in Brazilian energy
matrix towards the national bio-based economy. Greenhouse gas (GHG) emissions is
the most widely used indicator for assessing the environmental sustainability of
biodiesels and received particular attention among decision makers in business
and politics, as well as consumers. Former studies have been mainly focused on
the GHG emissions from the soybean cultivation, excluding other stages of the
biodiesel production. Here, we present a holistic view of the total GHG emissions
in four life cycle stages for soybean biodiesel. The aim of this study was to
assess the GHG emissions of Brazilian soybean biodiesel production system with an
integrated life cycle approach of four stages: agriculture, extraction,
production and distribution. Allocation of mass and energy was applied and
special attention was paid to the integrated and non-integrated industrial
production chain. The results indicated that the largest source of GHG emissions,
among four life cycle stages, is the agricultural stage (42-51%) for B100
produced in integrated systems and the production stage (46-52%) for B100
produced in non-integrated systems. Integration of industrial units resulted in
significant reduction in life cycle GHG emissions. Without the consideration of
LUC and assuming biogenic CO2 emissions is carbon neutral in our study, the
calculated life cycle GHG emissions for domestic soybean biodiesel varied from
23.1 to 25.8 gCO2eq. MJ-1 B100 and those for soybean biodiesel exported to EU
ranged from 26.5 to 29.2 gCO2eq. MJ-1 B100, which represent reductions by 65% up
to 72% (depending on the delivery route) of GHG emissions compared with the EU
benchmark for diesel fuel. Our findings from a life cycle perspective contributed
to identify the major GHG sources in Brazilian soybean biodiesel production
system and they can be used to guide mitigation priority for policy and decision
making. Projected scenarios in this study would be taken as references for
accounting the environmental sustainability of soybean biodiesel within a
domestic and global level.
PMID- 28493967
TI - Water permeation through the internal water pathway in activated GPCR rhodopsin.
AB - Rhodopsin is a light-driven G-protein-coupled receptor that mediates signal
transduction in eyes. Internal water molecules mediate activation of the receptor
in a rhodopsin cascade reaction and contribute to conformational stability of the
receptor. However, it remains unclear how internal water molecules exchange
between the bulk and protein inside, in particular through a putative solvent
pore on the cytoplasmic. Using all-atom molecular dynamics simulations, we
identified the solvent pore on cytoplasmic side in both the Meta II state and the
Opsin. On the other hand, the solvent pore does not exist in the dark-adapted
rhodopsin. We revealed two characteristic narrow regions located within the
solvent pore in the Meta II state. The narrow regions distinguish bulk and the
internal hydration sites, one of which is adjacent to the conserved structural
motif "NPxxY". Water molecules in the solvent pore diffuse by pushing or
sometimes jumping a preceding water molecule due to the geometry of the solvent
pore. These findings revealed a total water flux between the bulk and the protein
inside in the Meta II state, and suggested that these pathways provide water
molecules to the crucial sites of the activated rhodopsin.
PMID- 28493966
TI - Improving drug delivery strategies for lymphatic filariasis elimination in urban
areas in Ghana.
AB - The Global Program to Eliminate Lymphatic Filariasis (GPELF) advocates for the
treatment of entire endemic communities, in order to achieve its elimination
targets. LF is predominantly a rural disease, and achieving the required
treatment coverage in these areas is much easier compared to urban areas that are
more complex. In Ghana, parts of the Greater Accra Region with Accra as the
capital city are also endemic for LF. Mass Drug Administration (MDA) in Accra
started in 2006. However, after four years of treatment, the coverage has always
been far below the 65% epidemiologic coverage for interrupting transmission. As
such, there was a need to identify the reasons for poor treatment coverage and
design specific strategies to improve the delivery of MDA. This study therefore
set out to identify the opportunities and barriers for implementing MDA in urban
settings, and to develop appropriate strategies for MDA in these settings. An
experimental, exploratory study was undertaken in three districts in the Greater
Accra region. The study identified various types of non-rural settings, the
social structures, stakeholders and resources that could be employed for MDA.
Qualitative assessment such as in-depth interviews (IDIs) and focus group
discussions (FGDs) with community leaders, community members, health providers,
NGOs and other stakeholders in the community was undertaken. The study was
carried out in three phases: pre-intervention, intervention and post-intervention
phases, to assess the profile of the urban areas and identify reasons for poor
treatment coverage using both qualitative and quantitative research methods. The
outcomes from the study revealed that, knowledge, attitudes and practices of
community members to MDA improved slightly from the pre-intervention phase to the
post-intervention phase, in the districts where the interventions were readily
implemented by health workers. Many factors such as adequate leadership, funding,
planning and community involvement, were identified as being important in
improving implementation and coverage of MDA in the study districts. Implementing
MDA in urban areas therefore needs to be given significant consideration and
planning, if the required coverage rates are to be achieved. This paper, presents
the recommendations and strategies for undertaking MDA in urban areas.
PMID- 28493968
TI - The dead, hardened floral bracts of dispersal units of wild wheat function as
storage for active hydrolases and in enhancing seedling vigor.
AB - It is commonly assumed that the dead, hardened floral bracts of the dispersal
unit of grasses have been evolved to protect seeds from predation and / or assist
in fruit/caryopsis dispersal. While these structures have important agronomical
and economical implications, their adaptive value has not been fully explored. We
investigated the hypothesis that the maternally derived hardened floral bracts
have been evolved not just as a means for caryopsis protection and dispersal, but
also as storage for substances that might affect seed germination and seedling
vigor. Dead glumes as well as lemmas and paleas of wild emmer wheat (Triticum
turgidum var dicoccoides) were found to store and release upon hydration active
hydrolases including nucleases and chitinases. High nuclease activity was
released upon hydration from glumes derived from wild strains of wheat including
Triticum urartu and wild emmer wheat, while very low nuclease activity was
detected in glumes derived from domesticated, free-threshing wheat cultivars
(e.g., durum wheat). Germination from the intact dispersal unit of wild emmer
wheat was delayed, but post germination growth was better than those of separated
caryopses. Most notable was a significant increase in lateral root production on
seedlings germinated from the intact dispersal unit. Proteome analysis of wild
emmer wheat glumes revealed many proteins stored and released upon hydration
including S1-type nucleases, peptidases, antifungal hydrolases such as chitinases
and beta-1,3-glucanase as well as pectin acetylesterase, a protein involved in
cell wall degradation and remodeling. Also, reactive oxygen species (ROS)
detoxifying enzymes such as superoxide dismutase and ascorbate peroxidase were
overrepresented in dead glumes of wild emmer wheat. Thus our study highlighted
previously unknown features of the dispersal unit in wild wheat in which the
dead, hardened floral bracts enclosing the caryopsis store active hydrolases and
nutritional elements and probably growth promoting substances that facilitate
seed longevity and germination and increase seedling vigor.
PMID- 28493969
TI - Activation and inactivation of Bacillus pumilus spores by kiloelectron volt X-ray
irradiation.
AB - In this study, we investigated the inactivation efficacy of endospore-forming
bacteria, Bacillus pumilus, irradiated by low-energy X-rays of different beam
qualities. The different low-energy X-rays studied had cut-off energies of 50,
100 and 150 keV. Bacillus pumilus spores (in biological indicator strips) were
irradiated at step doses between 6.5 to 390 Gy. The resulting bacteria
populations were then quantified by a pour plate method. Results showed that X
rays of lower energies were more effective in inactivating bacterial spores. In
addition, an increment in bacterial population was observed at doses below 13Gy.
We attributed this increase to a radiation-induced activation of bacterial
spores. Four kinetic models were then evaluated for their prediction of bacterial
spore behavior under irradiation. This included: (i) first-order kinetics model;
(ii) Shull model; (iii) Sapru model; and (iv) probabilistic model. From R2 and
AIC analyses, we noted that the probabilistic model performed the best, followed
by the Sapru model. We highlighted that for simplicity in curve fitting the Sapru
model should be used instead of the probabilistic model. A 12-log reduction in
bacterial population (corresponding to a sterility assurance level of 10-6 as
required in the sterilization of medical devices) was computed to be achievable
at doses of 1000, 1600 and 2300 Gy for the three different X-ray cut-off energies
respectively. These doses are an order in magnitude lesser than that required in
gamma irradiation. This highlights the applicability of cheaper and safer table
top X-ray sources for sterilization application.
PMID- 28493970
TI - Elevation of secondary metabolites synthesis in Brassica campestris ssp.
chinensis L. via exogenous inoculation of Piriformospora indica with appropriate
fertilizer.
AB - This work evaluated the impact of exogenous soil inoculation of beneficial fungal
strain Piriformospora indica on phytochemical changes and the related genes
expression of Chinese cabbage (Brassica campestris ssp. chinensis L.) by
greenhouse pot experiments. High performance liquid chromatography (HPLC)
affirmed that among the different combinations of fungal and organic fertilizer
treatments, the phenolic acids and flavonoids were considerably enriched in
organic fertilizer and fungi (OP) followed by organic fertilizer, biochar, fungi
(OBP) treated plants. The antiradical activity was higher in OP (61.29%) followed
by P (60%) and organic fertilizer (OF) (53.84%) inoculated plants which
positively correlated with chlorophyll, carotenoids and flavonoids level
(P<0.05). Furthermore, results showed that the exogenous application of P. indica
significantly (P<0.05) enhanced plant growth, as well as stimulating the
activation of chlorophyll, carotenoids and other antioxidant related pathways.
The RT-qPCR analysis indicated that key FLS gene triggering the synthesis of
kaemferol was up-regulated by the inoculation of P. indica. In conclusion, the
results revealed that organic fertilizer and P. indica (OP) is the most
appropriate combination for improving phytochemical and antiradical properties in
Pakchoi.
PMID- 28493971
TI - Nonsense variant in COL7A1 causes recessive dystrophic epidermolysis bullosa in
Central Asian Shepherd dogs.
AB - A rare hereditary mechanobullous disorder called epidermolysis bullosa (EB)
causes blistering in the skin and the mucosal membranes. To date, nineteen EB
related genes have been discovered in human and other species. We describe here a
novel EB variant in dogs. Two newborn littermates of Central Asian Shepherd dogs
with severe signs of skin blistering were brought to a veterinary clinic and
euthanized due to poor prognosis. In post-mortem examination, the puppies were
shown to have findings in the skin and the mucosal membranes characteristic of
EB. A whole-genome sequencing of one of the affected puppies was performed to
identify the genetic cause. The resequencing data were filtered under a recessive
model against variants from 31 other dog genomes, revealing a homozygous case
specific nonsense variant in one of the known EB-causing genes, COL7A1
(c.4579C>T, p.R1527*). The variant results in a premature stop codon and likely
absence of the functional protein in the basement membrane of the skin in the
affected dogs. This was confirmed by immunohistochemistry using a COL7A1
antibody. Additional screening of the variant indicated full penetrance and breed
specificity at ~28% carrier frequency. In summary, this study reveals a novel
COL7A1 variant causing recessive dystrophic EB and provides a genetic test for
the eradication of the disease from the breed.
PMID- 28493973
TI - Prevalence of Coxiella burnetii in cattle at South Korean national breeding stock
farms.
AB - This is the first study to evaluate the serologic and molecular prevalence of
Coxiella burnetii in cattle at national breeding stock farms in South Korea.
These government farms have well-organized biosecurity and management systems to
prevent livestock diseases. Of the 736 cattle in this study, 77 tested positive
for antibodies against C. burnetii antigens (10.5%, 95% CI: 8.3-12.7) and 11 were
positive for a C. burnetti infection on PCR analysis (1.5%, 95% CI: 0.6-2.4).
Since the 16S rRNA sequences of C. burnetii from all 11 PCR-positive samples were
identical, three representative samples (C-CN-3 from the southern region, C-JJ-9
from Jeju Island, and C-CB-37 from the central region) are described in this
paper. These three sequences had 99.3-100% identity to those of C. burnetii
deposited in GenBank. These sequences clustered with those from USA, Japan, and
Greenland, underscoring the sequence similarity among C. burnetii isolates in
these countries. Because C. burnetii was detected in cattle at well-managed
national breeding stock farms, cattle at non-government operated farms may be
more likely to be exposed to C. burnetii in South Korea. Thus, continuous
surveillance and control strategies in animals and humans are required to prevent
the transmission of C. burnetii to humans.
PMID- 28493972
TI - Positive radionuclide imaging of miRNA expression using RILES and the human
sodium iodide symporter as reporter gene is feasible and supports a protective
role of miRNA-23a in response to muscular atrophy.
AB - MicroRNAs (miRNAs) are key players in many biological processes and are
considered as an emerging class of pharmacology drugs for diagnosis and therapy.
However to fully exploit the therapeutic potential of miRNAs, it is becoming
crucial to monitor their expression pattern using medical imaging modalities.
Recently, we developed a method called RILES, for RNAi-Inducible Luciferase
Expression System that relies on an engineered regulatable expression system to
switch-ON the expression of the luciferase gene when a miRNA of interest is
expressed in cells. Here we investigated whether replacing the luciferase
reporter gene with the human sodium iodide symporter (hNIS) reporter gene will be
also suited to monitor the expression of miRNAs in a clinical setting context. We
provide evidence that radionuclide imaging of miRNA expression using hNIS is
feasible although it is not as robust as when the luciferase reporter gene is
used. However, under appropriate conditions, we monitored the expression of
several miRNAs in cells, in the liver and in the tibialis anterior muscle of mice
undergoing muscular atrophy. We demonstrated that radiotracer accumulation in
transfected cells correlated with the induction of hNIS and with the expression
of miRNAs detected by real time PCR. We established the kinetic of miRNA-23a
expression in mice and demonstrated that this miRNA follows a biphasic expression
pattern characterized by a loss of expression at a late time point of muscular
atrophy. At autopsy, we found an opposite expression pattern between miRNA-23a
and one of the main transcriptional target of this miRNA, APAF-1, and as
downstream target, Caspase 9. Our results report the first positive monitoring of
endogenously expressed miRNAs in a nuclear medicine imaging context and support
the development of additional work to establish the potential therapeutic value
of miRNA-23 to prevent the damaging effects of muscular atrophy.
PMID- 28493974
TI - Serum alpha-1 Antitrypsin (AAT) antagonizes intrinsic apoptosis induction in
neutrophils from patients with systemic inflammatory response syndrome.
AB - Excessive neutrophil activation accompanied by delayed apoptotic cell death in
inflammatory conditions causes progressive damage of cells and tissues, leading
to life-threatening multiple organ dysfunction syndrome. Previous work suggested
that circulating serum factors during inflammation are critically involved in the
suppression of neutrophil cell death although the identity of these antiapoptotic
mediators remained elusive. In this study, we identified the acute phase protein
alpha-1 Antitrypsin (AAT) as a potent suppressor of staurosporine (STS)-induced
apoptosis in human neutrophils through a mechanism implicating caspases
independent pathways. We show here that serum levels of AAT, potentially in part
released by stimulated neutrophils, are markedly elevated in major trauma
patients suffering from systemic inflammatory response syndrome (SIRS). Notably,
AAT depletion from serum increased sensitivity of human neutrophils for STS
induced cell death. In fact, AAT was demonstrated to confer intrinsic apoptosis
resistance by preventing PKC/Akt inactivation and subsequent proteasomal
degradation of antiapoptotic Mcl-1 protein in response to STS treatment. Neither
MAP kinase ERK1/2 nor caspases were found to be involved in AAT-triggered
antiapoptotic pathways in neutrophils. In summary, these results establish a
novel pivotal role of circulating AAT in mediating survival by antagonizing the
proapoptotic action of the PKC inhibitor STS and should be considered for AAT
augmentation therapies in future.
PMID- 28493976
TI - "Passive victim - strong survivor"? Perceived meaning of labels applied to women
who were raped.
AB - Three experiments (total N = 464) were conducted in parallel with English- and
German-speaking participants to examine the perceived meanings and effects of the
labels "victim" versus "survivor" (and their German equivalents) when applied to
a woman who was raped. In Study 1 (N = 179), participants read a rape vignette
and then rated the meaning of the label it contained (either "victim" or
"survivor") on a 15-item semantic differential. Independent of language and
participant gender, "survivor" was perceived more positively overall (e.g., as
strong, brave, active) than was "victim" (weak, passive, but also innocent). In
Study 2 (N = 95), labels were varied within items assessing judgments of an
acquaintance-rape case (e.g., "Does the victim [survivor] ... carry a certain
responsibility for what happened?"), focusing on short-term outcomes. Significant
interaction effects of label and participants' gender emerged on case-related
judgments. Participants in both language samples judged "survivor" to be a less
appropriate term than "victim". In Study 3 (N = 190), participants read a text in
which a woman who had been raped labeled herself as either "victim" or
"survivor", focusing on the coping with sexual violence. As in Study 2, German
language participants showed no significant effects of the label on their case
judgments but rejected the term "survivor" as inappropriate; English-language
participants, by contrast, perceived the woman describing herself as "survivor"
to be more psychologically stable and regarded the use of both labels as
appropriate. Results are discussed in terms of their applied relevance for
communicating about sexual violence.
PMID- 28493975
TI - Molecular characterization, expression of chicken TBK1 gene and its effect on
IRF3 signaling pathway.
AB - TRAF family member-associated NF-kappaB activator (TANK)-binding kinase1 (TBK1)
is a serine-threonine kinase at the crossroads of multiple interferon (IFN)
inducing signaling pathways in innate immunity. The importance of TBK1 in
antiviral immunity is well established in mammal models, but in chicken, the
molecular characterization and potential function of TBK1 remain unclear. In the
present study, the open-reading frame (ORF) of chicken TBK1 (chTBK1) was cloned
and characterized. The sequencing results revealed that the chTBK1 ORF consists
of 2190 base pairs (bp) encoding a deduced protein of 729 amino acid residues.
Multiple sequence alignment analysis demonstrated chTBK1 similarity to other
birds and mammals, which indicates that it is evolutionarily conserved.
Quantitative real-time PCR (qRT-PCR) results showed that chTBK1 was ubiquitously
expressed in chicken tissues and expression was especially high in immune
tissues. In addition, the expression of chTBK1 was significantly up-regulated by
infection with avian leukosis virus subgroup J (ALV-J) both in vivo and in
chicken embryo fibroblasts (CEFs) challenged with ALV-J or stimulated with poly
I:C in vitro. Consistent with the activation of chTBK1, the interferon regulatory
factor 3 (IRF3) and IFNbeta gene in CEFs were also up-regulated after challenge
with ALV-J or polyI:C. In contrast, the expression of IRF3 and IFNbeta in CEFs
was significantly reduced by siRNA targeting the chTBK1 gene compared with a
negative control (NC) during ALV-J infection or polyI:C transfection. In
conclusion, our results demonstrated that chTBK1 may be an important
immunoregulator for IRF3 and IFNbeta induction in response to viral stimulation
in chicken.
PMID- 28493977
TI - Robust multiple frequency multiple power localization schemes in the presence of
multiple jamming attacks.
AB - Localization of the wireless sensor network is a vital area acquiring an
impressive research concern and called upon to expand more with the rising of its
applications. As localization is gaining prominence in wireless sensor network,
it is vulnerable to jamming attacks. Jamming attacks disrupt communication
opportunity among the sender and receiver and deeply impact the localization
process, leading to a huge error of the estimated sensor node position.
Therefore, detection and elimination of jamming influence are absolutely
indispensable. Range-based techniques especially Received Signal Strength (RSS)
is facing severe impact of these attacks. This paper proposes algorithms based on
Combination Multiple Frequency Multiple Power Localization (C-MFMPL) and Step
Function Multiple Frequency Multiple Power Localization (SF-MFMPL). The
algorithms have been tested in the presence of multiple types of jamming attacks
including capture and replay, random and constant jammers over a log normal
shadow fading propagation model. In order to overcome the impact of random and
constant jammers, the proposed method uses two sets of frequencies shared by the
implemented anchor nodes to obtain the averaged RSS readings all over the
transmitted frequencies successfully. In addition, three stages of filters have
been used to cope with the replayed beacons caused by the capture and replay
jammers. In this paper the localization performance of the proposed algorithms
for the ideal case which is defined by without the existence of the jamming
attack are compared with the case of jamming attacks. The main contribution of
this paper is to achieve robust localization performance in the presence of
multiple jamming attacks under log normal shadow fading environment with a
different simulation conditions and scenarios.
PMID- 28493978
TI - Identification of the SUMO E3 ligase PIAS1 as a potential survival biomarker in
breast cancer.
AB - Metastasis is the ultimate cause of breast cancer related mortality. Epithelial
mesenchymal transition (EMT) is thought to play a crucial role in the metastatic
potential of breast cancer. Growing evidence has implicated the SUMO E3 ligase
PIAS1 in the regulation of EMT in mammary epithelial cells and breast cancer
metastasis. However, the relevance of PIAS1 in human cancer and mechanisms by
which PIAS1 might regulate breast cancer metastasis remain to be elucidated.
Using tissue-microarray analysis (TMA), we report that the protein abundance and
subcellular localization of PIAS1 correlate with disease specific overall
survival of a cohort of breast cancer patients. In mechanistic studies, we find
that PIAS1 acts via sumoylation of the transcriptional regulator SnoN to suppress
invasive growth of MDA-MB-231 human breast cancer cell-derived organoids. Our
studies thus identify the SUMO E3 ligase PIAS1 as a prognostic biomarker in
breast cancer, and suggest a potential role for the PIAS1-SnoN sumoylation
pathway in controlling breast cancer metastasis.
PMID- 28493979
TI - Tissue lithography: Microscale dewaxing to enable retrospective studies on
formalin-fixed paraffin-embedded (FFPE) tissue sections.
AB - We present a new concept, termed tissue lithography (TL), and its implementation
which enables retrospective studies on formalin-fixed paraffin-embedded tissue
sections. Tissue lithography uses a microfluidic probe to remove microscale areas
of the paraffin layer on formalin-fixed paraffin-embedded biopsy samples. Current
practices in sample utilization for research and diagnostics require complete
deparaffinization of the sample prior to molecular testing. This imposes strong
limitations in terms of the number of tests as well as the time when they can be
performed on a single sample. Microscale dewaxing lifts these constraints by
permitting deprotection of a fraction of a tissue for testing while keeping the
remaining of the sample intact for future analysis. After testing, the sample can
be sent back to storage instead of being discarded, as is done in standard
workflows. We achieve this microscale dewaxing by hydrodynamically confining
nanoliter volumes of xylene on top of the sample with a probe head. We
demonstrate micrometer-scale, chromogenic and fluorescence-based
immunohistochemistry against multiple biomarkers (p53, CD45, HER2 and beta-actin)
on tonsil and breast tissue sections and microarrays. We achieve stain patterns
as small as 100 MUm * 50 MUm as well as multiplexed immunostaining within a
single tissue microarray core with a 20-fold time reduction for local dewaxing as
compared to standard protocols. We also demonstrate a 10-fold reduction in the
rehydration time, leading to lower processing times between different stains. We
further show the potential of TL for retrospective studies by sequentially
dewaxing and staining four individual cores within the same tissue microarray
over four consecutive days. By combining tissue lithography with the concept of
micro-immunohistochemistry, we implement each step of the IHC protocol-dewaxing,
rehydration and staining-with the same microfluidic probe head. Tissue
lithography brings a new level of versatility and flexibility in sample
processing and budgeting in biobanks, which may alleviate current sample
limitations for retrospective studies in biomarker discovery and drug screening.
PMID- 28493980
TI - Characterization of the juvenile green turtle (Chelonia mydas) microbiome
throughout an ontogenetic shift from pelagic to neritic habitats.
AB - The gut microbiome of herbivorous animals consists of organisms that efficiently
digest the structural carbohydrates of ingested plant material. Green turtles
(Chelonia mydas) provide an interesting model of change in these microbial
communities because they undergo a pronounced shift from a surface-pelagic
distribution and omnivorous diet to a neritic distribution and herbivorous diet.
As an alternative to direct sampling of the gut, we investigated the cloacal
microbiomes of juvenile green turtles before and after recruitment to neritic
waters to observe any changes in their microbial community structure. Cloacal
swabs were taken from individual turtles for analysis of the 16S rRNA gene
sequences using Illumina sequencing. One fecal sample was also obtained, allowing
for a preliminary comparison with the bacterial community of the cloaca. We found
significant variation in the juvenile green turtle bacterial communities between
pelagic and neritic habitats, suggesting that environmental and dietary factors
support different bacterial communities in green turtles from these habitats.
This is the first study to characterize the cloacal microbiome of green turtles
in the context of their ontogenetic shifts, which could provide valuable insight
into the origins of their gut bacteria and how the microbial community supports
their shift to herbivory.
PMID- 28493981
TI - Within-session decrement of the emission of licking bursts following reward
devaluation in rats licking for sucrose.
AB - We previously observed that dopamine D2-like receptor blockade in rats licking
for sucrose produced a within-session decrement of the emission of licking bursts
similar to the effect of either reward devaluation, or neuroleptics, on operant
responding for different rewards, which, accordingly, we interpreted as an
extinction-like effect. This implies that exposing animals to reward devaluation
would result in a drop of burst number taking place only after the contact with
the devalued reward. To test this prediction, we compared the difference in the
within-session time course of burst number in response to high (10%) versus low
(2%) concentration sucrose solutions, either in a condition of reward devaluation
(exposure to 2% after daily 10%), or in a condition which does not involve
changes in the reward value (two groups of subjects each repeatedly exposed to
only one of the two concentrations). Reward devaluation resulted in a within
session decrement of the burst number, with the response rate dropping only after
the contact with the devalued reward, as predicted. This response pattern was
reliably observed only in subjects at their first devaluation experience. In
contrast, exposure of separate groups of animals to the two different
concentrations yielded lower levels of burst number in the low concentration
group apparent since the beginning of the session, as previously observed with
dopamine D1-like receptor blockade. These results show that the analysis of burst
number, but not of burst size, reveals a specific activation pattern in response
to reward devaluation, which differs from the pattern observed comparing the
response to two different sucrose concentrations in separate groups of subjects,
i.e. in a condition not involving reward devaluation. Finally, the
characterisation of the experimental measures of the analysis of licking
microstructure in behaviourally (and psychologically) meaningful functional
terms, might be relevant for the investigation of the mechanisms underlying
behavioural activation and the related evaluation processes.
PMID- 28493982
TI - Comparison of spectral-domain optical coherence tomography for intra-retinal
layers thickness measurements between healthy and diabetic eyes among Chinese
adults.
AB - PURPOSE: To compare intra-retinal layer thickness measurements between eyes with
no or mild diabetic retinopathy (DR) and age-matched controls using Spectralis
spectral-domain optical coherence tomography (SD-OCT). METHODS: Cross-sectional
observational analysis study. High-resolution macular volume scans (30 degrees *
25 degrees ) were obtained for 133 type 2 diabetes mellitus (T2DM) patients with
no DR, 42 T2DM patients with mild DR and 115 healthy controls. The mean thickness
was measured in all 9 Early Treatment Diabetic Retinopathy Study (ETDRS) sectors
for 8 separate layers, inner retinal layer (IRL), outer retinal layer (ORL) and
total retina (TR), after automated segmentation. The ETDRS grid consisted of
three concentric circles of 1-, 3-, and 6-mm diameter. The superior, inferior,
temporal, and nasal sectors of the 3- and 6-mm circles were respectively
designated as S3, I3, T3, and N3 and S6, I6, T6, and N6. Linear regression
analyses were conducted to evaluate the associations between the intra-retinal
layer thicknesses, age, diabetes duration, fasting blood glucose and HbA1c.
RESULTS: The mean age and duration of T2DM were 61.1 and 13.7 years,
respectively. Although no significant differences in the average TR and ORL
volumes were observed among the groups, significant differences were found in the
volume and sectorial thicknesses of the inner plexiform layer (IPL), outer
plexiform layer (OPL) and IRL among the groups. In particular, the thicknesses of
the IPL (S3, T3, S6, I6 and T6 sectors) and the IRL (S6 sector) were decreased in
the no-DR group compared with the controls (P < 0.05). The thickness of the OPL
(S3, N3, S6 and N6 sectors) was thinner in the no-DR group than in mild DR (P <
0.05). The average IPL thickness was significantly negatively correlated with age
and the duration of diabetes. CONCLUSION: The assessment of the intra-retinal
layer thickness showed a significant decrease in the IPL and IRL thicknesses in
Chinese adults with T2DM, even in the absence of visible microvascular signs of
DR.
PMID- 28493983
TI - New opportunities and challenges to engineer disease resistance in cassava, a
staple food of African small-holder farmers.
PMID- 28493984
TI - Nasal airway epithelial cell IL-6 and FKBP51 gene expression and steroid
sensitivity in asthmatic children.
AB - BACKGROUND: Many asthmatic patients exhibit uncontrolled asthma despite high-dose
inhaled corticosteroids (ICS). Airway epithelial cells (AEC) have distinct
activation profiles that can influence ICS response. OBJECTIVES: A pilot study to
identify gene expression markers of AEC dysfunction and markers of corticosteroid
sensitivity in asthmatic and non-asthmatic control children, for comparison with
published reports in adults. METHODS: AEC were obtained by nasal brushings and
primary submerged cultures, and incubated in control conditions or in the
presence of 10 ng/ml TNFalpha, 10-8M dexamethasone, or both. RT-PCR-based
expression of FKBP51 (a steroid hormone receptor signalling regulator), NF-kB, IL
6, LIF (an IL-6 family neurotrophic cytokine), serpinB2 (which inhibits
plasminogen activation and promotes fibrin deposition) and porin (a marker of
mitochondrial mass) were determined. RESULTS: 6 patients without asthma (median
age 11yr; min-max: 7-13), 8 with controlled asthma (11yr, 7-13; median daily
fluticasone dose = 100 MUg), and 4 with uncontrolled asthma (12yr, 7-14; 1000 MUg
fluticasone daily) were included. Baseline expression of LIF mRNA was
significantly increased in uncontrolled vs controlled asthmatic children.
TNFalpha significantly increased LIF expression in uncontrolled asthma. A similar
trend was observed regarding IL-6. Dexamethasone significantly upregulated FKBP51
expression in all groups but the response was blunted in asthmatic children. No
significant upregulation was identified regarding NF-kB, serpinB2 and porin.
CONCLUSION: LIF and FKBP51 expression in epithelial cells were the most
interesting markers of AEC dysfunction/response to corticosteroid treatment.
PMID- 28493985
TI - Photodynamic antimicrobial chemotherapy with the novel amino acid-porphyrin
conjugate 4I: In vitro and in vivo studies.
AB - Photodynamic antimicrobial chemotherapy (PACT), as a novel and effective
therapeutic modality to eradicate drug resistant bacteria without provoking
multidrug resistance, has attracted increasing attention. This study examined the
antimicrobial efficacy of the novel cationic amino acid-porphyrin conjugate 4I
with four lysine groups against two different clinical isolated strains (drug
sensitive and multidrug resistant) of the Acinetobacter baumannii species and its
toxicity on murine dermal fibroblasts in vitro, as well as the therapeutic effect
of PACT on acute, potentially lethal multidrug resistant strain excisional wound
infections in vivo. The PACT protocol exposed 4I to illumination, exhibiting high
antimicrobial efficacy on two different strains due to a high yield of reactive
oxygen species (ROS) and non-selectivity to microorganisms. The photoinactivation
effects of 4I against two different strains were dose-dependent. At 3.9 MUM and
7.8 MUM, PACT induced 6 log units of inactivation of sensitive and multidrug
resistant strains. In contrast, 4I alone and illumination alone treatments had no
visibly antimicrobial effect. Moreover, cytotoxicity tests revealed the great
safety of the photosensitizer 4I in mice. In the in vivo study, we found 4I
mediated PACT was not only able to kill bacteria but also accelerated wound
recovery. Compared with non-treated mice, over 2.89 log reduction of multidrug
resistant Acinetobacter baumannii strain was reached in PACT treat mice at 24 h
post-treatment. These results imply that 4I-mediated PACT therapy is an effective
and safe alternative to conventional antibiotic therapy and has clinical
potential for superficial drug-resistant bacterial infections.
PMID- 28493987
TI - Barriers to utilization of childbirth services of a rural birthing center in
Nepal: A qualitative study.
AB - BACKGROUND: Maternal mortality and morbidity are public health problems in Nepal.
In rural communities, many women give birth at home without the support of a
skilled birth attendant, despite the existence of rural birthing centers. The aim
of this study was to explore the barriers and provide pragmatic recommendations
for better service delivery and use of rural birthing centers. METHODS: We
conducted 26 in-depth interviews with service users and providers, and three
focus group discussions with community key informants in a rural community of
Rukum district. We used the Adithya Cattamanchi logic model as a guiding
framework for data analysis. RESULTS: Irregular and poor quality services,
inadequate human and capital resources, and poor governance were health system
challenges which prevented service delivery. Contextual barriers including
difficult geography, poor birth preparedness practices, harmful culture practices
and traditions and low level of trust were also found to contribute to
underutilization of the birthing center. CONCLUSION: The rural birthing center
was not providing quality services when women were in need, which meant women did
not use the available services properly because of systematic and contextual
barriers. Approaches such as awareness-raising activities, local resource
mobilization, ensuring access to skilled providers and equipment and other long
term infrastructure development works could improve the quality and utilization
of childbirth services in the rural birthing center. This has resonance for other
centers in Nepal and similar countries.
PMID- 28493986
TI - Impact of treatment in long-term survival patients with follicular lymphoma: A
Spanish Lymphoma Oncology Group registry.
AB - BACKGROUND: Follicular lymphoma is the second most common non-Hodgkin lymphoma in
the United States and Europe. However, most of the prospective randomized studies
have very little follow-up compared to the long natural history of the disease.
The primary aim of this study was to investigate the long-term survival of our
series of patients with follicular lymphoma. PATIENTS AND METHODS: A total of
1074 patients with newly diagnosed FL were enrolled. Patients diagnosed were
prospectively enrolled from 1980 to 2013. RESULTS: Median follow-up was 54.9
months and median overall survival is over 20 years in our series. We analyzed
the patients who are still alive beyond 10 years from diagnosis in order to fully
assess the prognostic factors that condition this group. Out of 166 patients who
are still alive after more than 10 years of follow-up, 118 of them (73%) are free
of evident clinical disease. Variables significantly associated with survival at
10 years were stage < II (p <0.03), age < 60 years (p <0.0001), low FLIPI (p
<0.002), normal beta2 microglobulin (p <0.005), no B symptoms upon diagnosis (p
<0.02), Performance Status 0-1 (p <0.03) and treatment with anthracyclines and
rituximab (p <0.001), or rituximab (p <0.0001). CONCLUSIONS: A longer follow-up
and a large series demonstrated a substantial population of patients with
follicular lymphoma free of disease for more than 10 years.
PMID- 28493988
TI - Prediction of whole-body fat percentage and visceral adipose tissue mass from
five anthropometric variables.
AB - BACKGROUND: The conventional measurement of obesity utilises the body mass index
(BMI) criterion. Although there are benefits to this method, there is concern
that not all individuals at risk of obesity-associated medical conditions are
being identified. Whole-body fat percentage (%FM), and specifically visceral
adipose tissue (VAT) mass, are correlated with and potentially implicated in
disease trajectories, but are not fully accounted for through BMI evaluation. The
aims of this study were (a) to compare five anthropometric predictors of %FM and
VAT mass, and (b) to explore new cut-points for the best of these predictors to
improve the characterisation of obesity. METHODS: BMI, waist circumference (WC),
waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and waist/height0.5
(WHT.5R) were measured and calculated for 81 adults (40 women, 41 men; mean (SD)
age: 38.4 (17.5) years; 94% Caucasian). Total body dual energy X-ray
absorptiometry with Corescan (GE Lunar iDXA, Encore version 15.0) was also
performed to quantify %FM and VAT mass. Linear regression analysis, stratified by
sex, was applied to predict both %FM and VAT mass for each anthropometric
variable. Within each sex, we used information theoretic methods (Akaike
Information Criterion; AIC) to compare models. For the best anthropometric
predictor, we derived tentative cut-points for classifying individuals as obese
(>25% FM for men or >35% FM for women, or > highest tertile for VAT mass).
RESULTS: The best predictor of both %FM and VAT mass in men and women was WHtR.
Derived cut-points for predicting whole body obesity were 0.53 in men and 0.54 in
women. The cut-point for predicting visceral obesity was 0.59 in both sexes.
CONCLUSIONS: In the absence of more objective measures of central obesity and
adiposity, WHtR is a suitable proxy measure in both women and men. The proposed
DXA-%FM and VAT mass cut-offs require validation in larger studies, but offer
potential for improvement of obesity characterisation and the identification of
individuals who would most benefit from therapeutic intervention.
PMID- 28493989
TI - Dynamics of initial drop splashing on a dry smooth surface.
AB - We simulate the onset and evolution of the earliest splashing of an infinite
cylindrical liquid drop on a smooth dry solid surface. A tiny splash is observed
to be emitted out of the rim of the lamella in the early stage of the impact. We
find that the onset time of the splash is primarily dependent on the
characteristic timescale, which is defined by the impact velocity as well as the
drop radius, with no strong dependence on either the liquid viscosity or surface
tension. Three regimes are found to be responsible for different splashing
patterns. The outermost ejected droplets keep extending radially at a uniform
speed proportional to the impact speed. Finally, we discuss the underlying
mechanism which is responsible for the occurrence of the initial drop splash in
the study.
PMID- 28493990
TI - MiR-338-3p regulates neuronal maturation and suppresses glioblastoma
proliferation.
AB - Neurogenesis is a highly-regulated process occurring in the dentate gyrus that
has been linked to learning, memory, and antidepressant efficacy. MicroRNAs
(miRNAs) have been previously shown to play an important role in the regulation
of neuronal development and neurogenesis in the dentate gyrus via modulation of
gene expression. However, this mode of regulation is both incompletely described
in the literature thus far and highly multifactorial. In this study, we designed
sensors and detected relative levels of expression of 10 different miRNAs and
found miR-338-3p was most highly expressed in the dentate gyrus. Comparison of
miR-338-3p expression with neuronal markers of maturity indicates miR-338-3p is
expressed most highly in the mature neuron. We also designed a viral "sponge" to
knock down in vivo expression of miR-338-3p. When miR-338-3p is knocked down,
neurons sprout multiple primary dendrites that branch off of the soma in a
disorganized manner, cellular proliferation is upregulated, and neoplasms form
spontaneously in vivo. Additionally, miR-338-3p overexpression in glioblastoma
cell lines slows their proliferation in vitro. Further, low miR-338-3p expression
is associated with increased mortality and disease progression in patients with
glioblastoma. These data identify miR-338-3p as a clinically relevant tumor
suppressor in glioblastoma.
PMID- 28493991
TI - Changes in gene expression between a soybean F1 hybrid and its parents are
associated with agronomically valuable traits.
AB - Soybean [Glycine max (L.) Merr.] genetic diversity is limited because
domesticated soybean has undergone multiple genetic bottlenecks. Its progenitor,
the wild soybean [Glycine soja Siebold & Zucc], has not undergone the same
intense selection and is much more genetically diverse than domesticated soybean.
However, the agronomic importance of diversity in wild soybean is unclear, and
its weedy nature makes assessment difficult. To address this issue, we chose for
study a highly selected, adapted F4-derived progeny of wild soybean, NMS4-44-329.
This breeding line is derived from the hybridization between G. max cultivar
N7103 and G. soja PI 366122. Agronomic comparisons were made among N7103, NMS4-44
329 and their F1 and F2 progeny in replicated yield trials at two North Carolina
locations. Significant F1 mid-parent heterosis was observed at each location for
seed yield (189 and 223 kgha-1, P<0.05 and P<0.10, respectively), seed protein
content (1.1g/100g, P<0.01) and protein production per hectare (101 and 100 kgha
1, P<0.01 and P<0.06, respectively). Increased yield, seed protein content and
protein production per hectare in the hybrids suggested that wild soybean has the
potential to improve agronomic traits in applied breeding. Comparisons of
differentially-expressed genes in the hybrid vs. parents identified genes
associated with N metabolism. Non-additive changes in gene expression in the
hybrids relative to the parents could reasonably explain the improved protein
levels in the F1 hybrids. Changes in gene expression were influenced by
environmental effects; however, allele specific bias in the hybrids were well
correlated between environments. We propose that changes in gene expression, both
additive and non-additive, and changes in allele specific expression bias may
explain agronomic traits, and be valuable tools for plant breeders in the
assessment of breeding populations.
PMID- 28493992
TI - Correction: Distribution and evolution of stable single alpha-helices (SAH
domains) in myosin motor proteins.
AB - [This corrects the article DOI: 10.1371/journal.pone.0174639.].
PMID- 28493993
TI - Mechanism of down regulation of Na-H exchanger-2 in experimental colitis.
AB - BACKGROUND: The Na-H exchanger [NHE] performs an electroneutral uptake of NaCl
and water from the lumen of the gastrointestinal tract. There are several
distinct NHE isoforms, some of which show an altered expression in the
inflammatory bowel diseases (IBD). In this study, we examined a role of NHE-2 in
experimental colitis. METHODS: Colitis was induced in male Sprague-Dawley rats by
intra-rectal administration of trinitrobenzenesulphonic acid (TNBS). On day 6
post-TNBS, the animals were sacrificed, colonic and ileal segments were taken
out, cleaned with phosphate buffered saline and used in this study. RESULTS:
There was a significant decrease in the level of NHE-2 protein as measured by ECL
western blot analysis and confocal immunofluorescence microscopy. The levels of
NHE-2 mRNA and heteronuclear RNA measured by an end-point RT-PCR and a real time
PCR were also decreased significantly in the inflamed colon. However, there was
no change in the level of NHE-2 protein in response to in vitro TNF-alpha
treatment of uninflamed rat colonic segment. These changes were selective and
localized to the colon as actin, an internal control, remained unchanged.
Confocal immunofluorescence microscopy revealed co-localization of NHE-2 and NHE
3 in the brush borders of colonic epithelial cells. Inflamed colon showed a
significant increase in myeloperoxidase activity and colon hypertrophy. In
addition, there was a significant decrease in body weight and goblet cells' mucin
staining in the TNBS treated colon. These changes were not conspicuous in the non
inflamed ileum. CONCLUSIONS: These findings demonstrate suppression of NHE-2
expression on the brush borders in the colonic epithelial cells which is
regulated transcriptionally. However a role of TNF-alpha in the regulation of NHE
2 is discounted in the present model of colitis. This decrease in the NHE-2
expression will lead to a loss of electrolyte and water uptake thus contributing
to the symptoms associated with IBD.
PMID- 28493995
TI - Influence of site index on the relationship between forest net primary
productivity and stand age.
AB - Previous studies show that forest net primary productivity (NPP) varies
pronouncedly with stand age, and these variations play a crucial role in
determining forest carbon sinks or sources at regional scales. Some forest carbon
cycling models, eg. InTEC (The integrated terrestrial ecosystem C-budget model),
calculates annual forest NPP in the long term according to normalized NPP-age
relationships and the reference forest NPP at a given age. Therefore, the
accurate NPP-age relationship is important for forest NPP estimation. In this
study, NPP at various stand ages for twelve major forest stand types in
Heilongjiang Province in northeast China is derived from yield tables with
consideration of the total biomass increment and foliage and fine-root turnovers.
Similar to previous studies, our results also show that forest NPP increases
quickly at young ages, reaches the maximum value at middle age (10-40 years old),
and then decreases to a relative stable level at old ages. However, we
additionally found that forests under better site conditions have faster growth
rates in young ages and steeper declines after reaching the maximum. Therefore,
when the NPP-age curves for different site indices are normalized against the
maximum value of each curve, there are significant differences among them. These
differences have implications on the methodology for estimating the spatial
distribution of forest carbon sources and sinks.
PMID- 28493994
TI - Spatiotemporal analysis of microbial community dynamics during seasonal
stratification events in a freshwater lake (Grand Lake, OK, USA).
AB - Many freshwater lakes undergo seasonal stratification, where the formation of
phototrophic blooms in the epilimnion and subsequent sedimentation induces
hypoxia/anoxia in the thermocline and hypolimnion. This autochthonously produced
biomass represents a major seasonal organic input that impacts the entire
ecosystem. While the limnological aspects of this process are fairly well
documented, relatively little is known regarding the microbial community response
to such events, especially in the deeper anoxic layers of the water column. Here,
we conducted a spatiotemporal survey of the particle-associated and free-living
microbial communities in a warm monomictic freshwater reservoir (Grand Lake O'
the Cherokees) in northeastern Oklahoma, USA. Pre-stratification samples (March)
harbored a homogeneous community throughout the oxygenated water column dominated
by typical oligotrophic aquatic lineages (acl clade within Actinobacteria, and
Flavobacterium within the Bacteroidetes). The onset of phototrophic blooming in
June induced the progression of this baseline community into two distinct
trajectories. Within the oxic epilimnion, samples were characterized by the
propagation of phototrophic (Prochlorococcus), and heterotrophic (Planctomycetes,
Verrucomicrobia, and Beta-Proteobacteria) lineages. Within the oxygen-deficient
thermocline and hypolimnion, the sedimentation of surface biomass induced the
development of a highly diverse community, with the enrichment of Chloroflexi,
"Latescibacteria", Armatimonadetes, and Delta-Proteobacteria in the particle
associated fraction, and Gemmatimonadetes and "Omnitrophica" in the free-living
fraction. Our work documents the development of multiple spatially and temporally
distinct niches during lake stratification, and supports the enrichment of
multiple yet-uncultured and poorly characterized lineages in the lake's deeper
oxygen-deficient layers, an ecologically relevant microbial niche that is often
overlooked in lakes diversity surveys.
PMID- 28493996
TI - Left ventricular functional, structural and energetic effects of normal aging:
Comparison with hypertension.
AB - OBJECTIVES: Both aging and hypertension are significant risk factors for heart
failure in the elderly. The purpose of this study was to determine how aging,
with and without hypertension, affects left ventricular function. METHODS: Cross
sectional study of magnetic resonance imaging and 31P spectroscopy-based
measurements of left ventricular structure, global function, strains, pulse wave
velocity, high energy phosphate metabolism in 48 normal subjects and 40 treated
hypertensive patients (though no other cardiovascular disease or diabetes)
stratified into 3 age deciles from 50-79 years. RESULTS: Normal aging was
associated with significant increases in systolic blood pressure, vascular
stiffness, torsion, and impaired diastolic function (all P<0.05). Age-matched
hypertension exacerbated the effects of aging on systolic pressure, and diastolic
function. Hypertension alone, and not aging, was associated with increased left
ventricular mass index, reduced energetic reserve, reduced longitudinal
shortening and increased endocardial circumferential shortening (all P<0.05).
Multiple linear regression analysis showed that these unique hypertensive
features were significantly related to systolic blood pressure (P<0.05).
CONCLUSIONS: 1) Hypertension adds to the age-related changes in systolic blood
pressure and diastolic function; 2) hypertension is uniquely associated with
changes in several aspects of left ventricular structure, function, systolic
strains, and energetics; and 3) these uniquely hypertensive-associated parameters
are related to the level of systolic blood pressure and so are potentially
modifiable.
PMID- 28493998
TI - Metabolomics analysis: Finding out metabolic building blocks.
AB - In this paper we propose a new methodology for the analysis of metabolic
networks. We use the notion of strongly connected components of a graph, called
in this context metabolic building blocks. Every strongly connected component is
contracted to a single node in such a way that the resulting graph is a directed
acyclic graph, called a metabolic DAG, with a considerably reduced number of
nodes. The property of being a directed acyclic graph brings out a background
graph topology that reveals the connectivity of the metabolic network, as well as
bridges, isolated nodes and cut nodes. Altogether, it becomes a key information
for the discovery of functional metabolic relations. Our methodology has been
applied to the glycolysis and the purine metabolic pathways for all organisms in
the KEGG database, although it is general enough to work on any database. As
expected, using the metabolic DAGs formalism, a considerable reduction on the
size of the metabolic networks has been obtained, specially in the case of the
purine pathway due to its relative larger size. As a proof of concept, from the
information captured by a metabolic DAG and its corresponding metabolic building
blocks, we obtain the core of the glycolysis pathway and the core of the purine
metabolism pathway and detect some essential metabolic building blocks that
reveal the key reactions in both pathways. Finally, the application of our
methodology to the glycolysis pathway and the purine metabolism pathway reproduce
the tree of life for the whole set of the organisms represented in the KEGG
database which supports the utility of this research.
PMID- 28493999
TI - Leopard in a tea-cup: A study of leopard habitat-use and human-leopard
interactions in north-eastern India.
AB - There is increasing evidence of the importance of multi-use landscapes for the
conservation of large carnivores. However, when carnivore ranges overlap with
high density of humans, there are often serious conservation challenges. This is
especially true in countries like India where loss of peoples' lives and property
to large wildlife are not uncommon. The leopard (Panthera pardus) is a large
felid that is widespread in India, often sharing landscapes with high human
densities. In order to understand the ecology of leopards in a human use
landscape and the nature of human-leopard interactions, we studied (i) the
spatial and temporal distribution and the characteristics of leopard attacks on
people, (ii) the spatial variability in the pattern of habitat use by the
leopard, and (iii) the spatial relationship between attack locations and habitat
use by leopards. The study site, located in northern West Bengal, India, is a
densely populated mixed-use landscape of 630 km2, comprising of forests, tea
plantations, agriculture fields, and human settlements. A total of 171 leopard
attacks on humans were reported between January 2009 and March 2016, most of
which occurred within the tea-gardens. None of the attacks was fatal. We found
significant spatial clustering of locations of leopard attacks on humans.
However, most of the attacks were restricted to certain tea estates and occurred
mostly between January and May. Analysis of habitat use by leopards showed that
the probability of use of areas with more ground vegetation cover was high while
that of areas with high density of buildings was low. However, locations of
leopard attacks on people did not coincide with areas that showed a higher
probability of use by leopards. This indicates that an increased use of an area
by leopards, by itself, does not necessarily imply an increase in attacks on
people. The spatial and temporal clustering of attack locations allowed us to use
this information to prioritize areas to focus mitigation activities in order
reduce negative encounters between people and leopards in this landscape which
has had a long history of conflict.
PMID- 28493997
TI - Adenosine A1 receptor activation increases myocardial protein S-nitrosothiols and
elicits protection from ischemia-reperfusion injury in male and female hearts.
AB - Nitric oxide (NO) plays an important role in cardioprotection, and recent work
from our group and others has implicated protein S-nitrosylation (SNO) as a
critical component of NO-mediated protection in different models, including
ischemic pre- and post-conditioning and sex-dependent cardioprotection. However,
studies have yet to examine whether protein SNO levels are similarly increased
with pharmacologic preconditioning in male and female hearts, and whether an
increase in protein SNO levels, which is protective in male hearts, is sufficient
to increase baseline protection in female hearts. Therefore, we pharmacologically
preconditioned male and female hearts with the adenosine A1 receptor agonist N6
cyclohexyl adenosine (CHA). CHA administration prior to ischemia significantly
improved functional recovery in both male and female hearts compared to baseline
in a Langendorff-perfused heart model of ischemia-reperfusion injury (% of
preischemic function +/- SE: male baseline: 37.5+/-3.4% vs. male CHA: 55.3+/
3.2%; female baseline: 61.4+/-5.7% vs. female CHA: 76.0+/-6.2%). In a separate
set of hearts, we found that CHA increased p-Akt and p-eNOS levels. We also used
SNO-resin-assisted capture with LC-MS/MS to identify SNO proteins in male and
female hearts, and determined that CHA perfusion induced a modest increase in
protein SNO levels in both male (11.4%) and female (12.3%) hearts compared to
baseline. These findings support a potential role for protein SNO in a model of
pharmacologic preconditioning, and provide evidence to suggest that a modest
increase in protein SNO levels is sufficient to protect both male and female
hearts from ischemic injury. In addition, a number of the SNO proteins identified
with CHA treatment were also observed with other forms of cardioprotective
stimuli in prior studies, further supporting a role for protein SNO in
cardioprotection.
PMID- 28494000
TI - Validating Bayesian truth serum in large-scale online human experiments.
AB - Bayesian truth serum (BTS) is an exciting new method for improving honesty and
information quality in multiple-choice survey, but, despite the method's
mathematical reliance on large sample sizes, existing literature about BTS only
focuses on small experiments. Combined with the prevalence of online survey
platforms, such as Amazon's Mechanical Turk, which facilitate surveys with
hundreds or thousands of participants, BTS must be effective in large-scale
experiments for BTS to become a readily accepted tool in real-world applications.
We demonstrate that BTS quantifiably improves honesty in large-scale online
surveys where the "honest" distribution of answers is known in expectation on
aggregate. Furthermore, we explore a marketing application where "honest" answers
cannot be known, but find that BTS treatment impacts the resulting distributions
of answers.
PMID- 28494001
TI - Partial spleen embolization reduces the risk of portal hypertension-induced upper
gastrointestinal bleeding in patients not eligible for TIPS implantation.
AB - INTRODUCTION: Upper gastrointestinal bleeding (UGIB) is a severe and life
threatening complication among patients with portal hypertension (PH). Covered
transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice
for patients with refractory or recurrent UGIB despite pharmacological and
endoscopic therapy. In some patients, TIPS implantation is not possible due to co
morbidity or vascular disorders. Spleen embolization (SE) may be a promising
alternative in this setting. MATERIALS AND METHODS: We retrospectively analyzed 9
patients with PH-induced UGIB who underwent partial SE between 2012 and 2016. All
patients met the following criteria: (i) upper gastrointestinal hemorrhage with
primary or secondary failure of endoscopic interventions and (ii) TIPS
implantation not possible. Each patient was followed for at least 6 months after
embolization. RESULTS: Five patients (56%) suffered from cirrhotic PH, 4 patients
(44%) from non-cirrhotic PH. UGIB occured in terms of refractory hemorrhage from
gastric varices (3/9; 33%), hemorrhage from esophageal varices (3/9; 33%), and
finally, hemorrhage from portal-hypertensive gastropathy (3/9; 33%). None of the
patients treated with partial SE experienced re-bleeding episodes or required
blood transfusions during a total follow-up time of 159 months, including both
patients with cirrhotic- and non-cirrhotic PH. DISCUSSION: Partial SE, as a
minimally invasive intervention with low procedure-associated complications, may
be a valuable alternative for patients with recurrent PH-induced UGIB refractory
to standard therapy.
PMID- 28494002
TI - Involvement of Band3 in the efflux of sphingosine 1-phosphate from erythrocytes.
AB - Sphingosine 1-phosphate (S1P) is a bioactive lipid mediator that is thought to be
involved in various diseases. Although the main source of S1P in the plasma is
erythrocytes, how S1P is exported from erythrocytes has not been elucidated. When
we differentiated K562 cells into erythroblast-like cells with sodium butyrate,
we observed that the efflux of S1P was increased without increased expression of
previously proposed S1P transporters, while the expression levels of Band3 were
increased. Therefore, in this study, we investigated the involvement of Band 3,
the most characteristic membranous transporter for erythrocytes, in S1P efflux,
using 4,4'-diisothiocyanatodihydrostilbene-2,2'-disulfonic acid, disodium salt
(H2DIDS), which is an inhibitor of Band3. First, we treated human washed
erythrocytes with H2DIDS and found that H2DIDS decreased the S1P levels in the
supernatant, while it increased the cellular S1P contents. Next, when we injected
H2DIDS into mice, the plasma S1P level was significantly decreased. Finally, when
we overexpressed or suppressed Band3 in K562 cells, S1P efflux was enhanced or
decreased, respectively, while the overexpression of Band3 in HEK293 cells did
not modulate S1P efflux. These results suggested the possible involvement of
Band3 in the transport of S1P, a multi-functional bioactive phospholipid, from
erythrocytes.
PMID- 28494004
TI - Increasing land-use intensity reverses the relative occupancy of two quadrupedal
scavengers.
AB - Human land use is continuously altering the natural environment, yet the greater
ecological implications of this change for many groups that are key to healthy
ecosystem functioning remains uncharacterised in the tropics. Terrestrial
scavenging vertebrates are one such group, providing integral ecosystem services
through the removal of carrion which is a crucial component of both nutrient
cycling and disease dynamics. To explore how anthropogenic processes may affect
forest scavengers, we investigated the changes in the relative occupancy of two
important terrestrial scavengers along a gradient of land use intensity, ranging
from protected forest to oil palm plantation in Borneo. We found the Malay civet
(Viverra tangalunga) had highest, albeit variable, occupancy in areas of low land
use intensity and the Southeast Asian water monitor (Varanus salvator
macromaculatus) had highest occupancy in areas of high land use intensity. Land
use had no effect on the combined occupancy of the two species. In high land use
intensity sites, individual water monitors were larger and had better body
condition, but at population level had a highly biased sex ratio with more males
than females and increased signs of intraspecific conflict. We did not assess
scavenging rate or efficiency as a process, but the high occupancy rates and
apparent health of the scavengers in high land use intensity landscapes suggests
this ecological process is robust to land use change.
PMID- 28494003
TI - P2Y6 receptors are involved in mediating the effect of inactivated avian
influenza virus H5N1 on IL-6 & CXCL8 mRNA expression in respiratory epithelium.
AB - One of the key pathophysiologies of H5N1 infection is excessive proinflammatory
cytokine response (cytokine storm) characterized by increases in IFN-beta, TNF
alpha, IL-6, CXCL10, CCL4, CCL2 and CCL5 in the respiratory tract. H5N1-induced
cytokine release can occur via an infection-independent mechanism, however,
detail of the cellular signaling involved is poorly understood. To elucidate this
mechanism, the effect of inactivated (beta-propiolactone-treated) H5N1 on the
cytokine and chemokine mRNA expression in 16HBE14o- human respiratory epithelial
cells was investigated. We found that the inactivated-H5N1 increased mRNA for IL
6 and CXCL8 but not TNF-alpha, CCL5 or CXCL10. This effect of the inactivated
H5N1 was inhibited by sialic acid receptor inhibitor (alpha-2,3 sialidase),
adenosine diphosphatase (apyrase), P2Y receptor (P2YR) inhibitor (suramin), P2Y6R
antagonist (MRS2578), phospholipase C inhibitor (U73122), protein kinase C
inhibitors (BIM and Go6976) and cell-permeant Ca2+ chelator (BAPTA-AM).
Inhibitors of MAPK signaling, including of ERK1/2 (PD98059), p38 MAPK (SB203580)
and JNK (SP600125) significantly suppressed the inactivated-H5N1-induced mRNA
expression of CXCL8. On the other hand, the inactivated-H5N1-induced mRNA
expression of IL-6 was inhibited by SB203580, but not PD98059 or SP600125,
whereas SN-50, an inhibitor of NF-kappaB, inhibited the effect of virus on mRNA
expression of both of IL-6 and CXCL8. Taken together, our data suggest that,
without infection, inactivated-H5N1 induces mRNA expression of IL-6 and CXCL8 by
a mechanism, or mechanisms, requiring interaction between viral hemagglutinin and
alpha-2,3 sialic acid receptors at the cell membrane of host cells, and involves
activation of P2Y6 purinergic receptors.
PMID- 28494005
TI - Relationship between regulatory pattern of gene expression level and gene
function.
AB - Regulation of gene expression levels is essential for all living systems and
transcription factors (TFs) are the main regulators of gene expression through
their ability to repress or induce transcription. A balance between synthesis and
degradation rates controls gene expression levels. To determine which rate is
dominant, we analyzed the correlation between expression levels of a TF and its
regulated gene based on a mathematical model. We selected about 280,000
expression patterns of 355 TFs and 647 regulated genes using DNA microarray data
from the Gene Expression Omnibus (GEO) data repository. Based on our model,
correlation between the expressions of TF-regulated gene pairs corresponds to
tuning of the synthesis rate, whereas no correlation indicates excessive
synthesis and requires tuning of the degradation rate. The gene expression
relationships between TF-regulated gene pairs were classified into four types
that correspond to different gene regulatory mechanisms. It was surprising that
fewer than 20% of these genes were governed by the familiar regulatory mechanism,
i.e., through the synthesis rate. Moreover, we performed pathway analysis and
found that each classification type corresponded to distinct gene functions:
cellular regulation pathways were dominant in the type with synthesis rate
regulation and terms associated with diseases such as cancer, Parkinson's
disease, and Alzheimer's disease were dominant in the type with degradation rate
regulation. Interestingly, these diseases are caused by the accumulation of
proteins. These results indicated that gene expression is regulated structurally,
not arbitrarily, according to the gene function. This funding is indicative of a
systematic control of transcription processes at the whole-cell level.
PMID- 28494006
TI - The change of longitudinal relaxation rate in oxygen enhanced pulmonary MRI
depends on age and BMI but not diffusing capacity of carbon monoxide in healthy
never-smokers.
AB - OBJECTIVE: Oxygen enhanced pulmonary MRI is a promising modality for functional
lung studies and has been applied to a wide range of pulmonary conditions. The
purpose of this study was to characterize the oxygen enhancement effect in the
lungs of healthy, never-smokers, in light of a previously established
relationship between oxygen enhancement and diffusing capacity of carbon monoxide
in the lung (DL,CO) in patients with lung disease. METHODS: In 30 healthy never
smoking volunteers, an inversion recovery with gradient echo read-out (Snapshot
FLASH) was used to quantify the difference in longitudinal relaxation rate, while
breathing air and 100% oxygen, DeltaR1, at 1.5 Tesla. Measurements were performed
under multiple tidal inspiration breath-holds. RESULTS: In single parameter
linear models, DeltaR1 exhibit a significant correlation with age (p = 0.003) and
BMI (p = 0.0004), but not DL,CO (p = 0.33). Stepwise linear regression of DeltaR1
yields an optimized model including an age-BMI interaction term. CONCLUSION: In
this healthy, never-smoking cohort, age and BMI are both predictors of the change
in MRI longitudinal relaxation rate when breathing oxygen. However, DL,CO does
not show a significant correlation with the oxygen enhancement. This is possibly
because oxygen transfer in the lung is not diffusion limited at rest in healthy
individuals. This work stresses the importance of using a physiological model to
understand results from oxygen enhanced MRI.
PMID- 28494007
TI - Child malnutrition in sub-Saharan Africa: A meta-analysis of demographic and
health surveys (2006-2016).
AB - BACKGROUND: Sub-Saharan Africa has one of the highest levels of child
malnutrition globally. Therefore, a critical look at the distribution of
malnutrition within its sub-regions is required to identify the worst affected
areas. This study provides a meta-analysis of the prevalence of malnutrition
indicators (stunting, wasting and underweight) within four sub-regions of sub
Saharan Africa. METHODS: Cross-sectional data from the most recent Demographic
and Health Surveys (2006-2016) of 32 countries in sub-Saharan Africa were used.
The countries were grouped into four sub-regions (East Africa, West Africa,
Southern Africa and Central Africa), and a meta-analysis was conducted to
estimate the prevalence of each malnutrition indicator within each of the sub
regions. Significant heterogeneity was detected among the various surveys (I2
>50%), hence a random effect model was used, and sensitivity analysis was
performed, to examine the effects of outliers. Stunting was defined as HAZ<-2;
wasting as WHZ<-2 and underweight as WAZ<-2. RESULTS: Stunting was highest in
Burundi (57.7%) and Malawi (47.1%) in East Africa; Niger (43.9%), Mali (38.3%),
Sierra Leone (37.9%) and Nigeria (36.8%) in West Africa; Democratic Republic of
Congo (42.7%) and Chad (39.9%) in Central Africa. Wasting was highest in Niger
(18.0%), Burkina Faso (15.50%) and Mali (12.7%) in West Africa; Comoros (11.1%)
and Ethiopia (8.70%) in East Africa; Namibia (6.2%) in Southern Africa; Chad
(13.0%) and Sao Tome & Principle (10.5%) in Central Africa. Underweight was
highest in Burundi (28.8%) and Ethiopia (25.2%) in East Africa; Niger (36.4%),
Nigeria (28.7%), Burkina Faso (25.7%), Mali (25.0%) in West Africa; and Chad
(28.8%) in Central Africa. CONCLUSION: The prevalence of malnutrition was highest
within countries in East Africa and West Africa compared to the WHO Millennium
development goals target for 2015. Appropriate nutrition interventions need to be
prioritised in East Africa and West Africa if sub-Saharan Africa is to meet the
WHO global nutrition target of improving maternal, infant and young child
nutrition by 2025.
PMID- 28494008
TI - Blocking of stromal interaction molecule 1 expression influence cell
proliferation and promote cell apoptosis in vitro and inhibit tumor growth in
vivo in head and neck squamous cell carcinoma.
AB - Calcium signal plays an important role in a variety of cancer cell metabolism,
but knowledge on its role in head and neck squamous cell carcinoma (HNSCC) is
limited. Store-operated calcium entry (SOCE) is the principal Ca2+ entry
mechanism that maintains calcium concentration and produces calcium signal in non
excitable cells. SOCE is triggered by stromal interaction molecule 1 (STIM1),
which is located in endoplasmic reticulum (ER) as Ca2+ sensor. Although, many
studies demonstrated that STIM1 and SOCE play important functions in the
regulation of many cancer progressions, their clinical relevance in HNSCC remains
unclear. In this study, STIM1 expression levels notably increased in 89% HNSCC
tissues compared with those in adjacent normal tissues. Meanwhile, this
overexpression was close associated with tumor size but not with neck lymph node
metastasis. Thus, this study mainly focuses on STIM1 function in HNSCC tumor
growth. Three HNSCC cell lines, namely, TSCCA (oral cancer cell line) and Hep2
(laryngeal cell line) with high STIM1 expression levels and Tb3.1 (oral cancer
cell line) with STIM1 expression level lower than previous two cell lines, were
selected for in vitro study. Downregulated STIM1 expression levels in TSCCA and
Hep2 arrested cells in G0/G1 stages, promoted cell apoptosis, and inhibited cell
proliferation. By contrast, upregulated STIM1 expression in Tb3.1 inhibited cell
apoptosis and promoted cell proliferation. Induced by thapsigargin (TG), ER
stress was amplified when STIM1 expression was downregulated but was attenuated
as STIM1 expression was upregulated. Furthermore, TSCCA cell xenograft models
confirmed that STIM1 could promote HNSCC tumor growth in vivo. The present study
provides new insight into HNSCC molecular mechanism and potential therapeutic
target through targeting SOCE-dependent process. However, whether STIM1
participates in HNSCC metastasis requires further study.
PMID- 28494009
TI - Postnatal changes and sexual dimorphism in collagen expression in mouse skin.
AB - To investigate sexual dimorphism and postnatal changes in skin collagen
expression, mRNA levels of collagens and their regulatory factors in male and
female skin were examined during the first 120 days of age by quantitative
realtime PCR. Levels of mRNAs encoding extracellular matrices did not show any
differences between male and female mice until day 15. Col1a1 and Col1a2 mRNAs
noticeably increased at day 30 and remained at high levels until day 120 in male
mice, while those in female mice remained at low levels during the period.
Consistent with the mRNA expression, pepsin-soluble type I collagen contents in
skin was very high in mature male as compared to female. Col3a1 mRNA in male mice
also showed significantly high level at day 120 as compared to female. On the
other hand, expression of mRNAs encoding TGF-betas and their receptors did not
show apparent sexual dimorphism although small significant differences were
observed at some points. Castration at 60 days of age resulted in a significant
decrease in type I collagen mRNA expression within 3 days, and noticeably
decreased expression of all fibril collagen mRNAs examined within 14 days, while
administration of testosterone tube maintained the mRNA expression at high
levels. Despite the in vivo effect of testosterone, administration of
physiological concentrations of testosterone did not affect fibril collagen mRNA
expression in either human or mouse skin fibroblasts in vitro, suggesting that
testosterone does not directly affect collagen expression in fibroblasts. In
summary, present study demonstrated dynamic postnatal changes in expression of
collagens and their regulatory factors, and suggest that testosterone and its
effects on collagen expression are responsible for the skin sexual dimorphism but
the effects of testosterone is not due to direct action on dermal fibroblasts.
PMID- 28494010
TI - Calcification in dermal fibroblasts from a patient with GGCX syndrome accompanied
by upregulation of osteogenic molecules.
AB - Gamma-glutamyl carboxylase (GGCX) gene mutation causes GGCX syndrome (OMIM:
137167), which is characterized by pseudoxanthoma elasticum (PXE)-like symptoms
and coagulation impairment. Here, we present a 55-year-old male with a novel
homozygous deletion mutation, c.2,221delT, p.S741LfsX100, in the GGCX gene.
Histopathological examination revealed calcium deposits in elastic fibers and
vessel walls, and collagen accumulation in the mid-dermis. Studies of dermal
fibroblasts from the patient (GGCX dermal fibroblasts) demonstrated that the
mutated GGCX protein was larger, but its expression level and intracellular
distribution were indistinguishable from those of the wild-type GGCX protein.
Immunostaining and an enzyme-linked immunosorbent assay showed an increase in
undercarboxylated matrix gamma-carboxyglutamic acid protein (ucMGP), a
representative substrate of GGCX and a potent calcification inhibitor, indicating
that mutated GGCX was enzymatically inactive. Under osteogenic conditions,
calcium deposition was exclusively observed in GGCX dermal fibroblasts.
Furthermore, GGCX dermal fibroblast cultures contained 23- and 7.7-fold more
alkaline phosphatase (ALP)-positive cells than normal dermal fibroblast cultures
(n = 3), without and with osteogenic induction, respectively. Expression and
activity of ALP were higher in GGCX dermal fibroblasts than in normal dermal
fibroblasts upon osteogenic induction. mRNA levels of other osteogenic markers
were also higher in GGCX dermal fibroblasts than in normal dermal fibroblasts,
which including bone morphogenetic protein 6, runt-related transcription factor
2, and periostin (POSTN) without osteogenic induction; and osterix, collagen type
I alpha 2, and POSTN with osteogenic induction. Together, these data indicate
that GGCX dermal fibroblasts trans-differentiate into the osteogenic lineage.
This study proposes another mechanism underlying aberrant calcification in
patients with GGCX syndrome.
PMID- 28494011
TI - Changes in the use practitioner-based complementary and alternative medicine over
time in Canada: Cohort and period effects.
AB - BACKGROUND: The use of complementary and alternative medicine (CAM) is growing.
However the factors contributing to changes over time and to birth cohort
differences in CAM use are not well understood. SETTING: We used data from 10186
participants, who were aged 20-69 years at the first cycle of data collection in
the longitudinal component of the Canadian National Population Health Survey
(1994/95-2010/11). We examined chiropractic and other practitioner-based CAM use
with a focus on five birth cohorts: pre-World War II (born 1925-1934); World War
II (born 1935-1944); older baby boomers (born 1945-1954); younger baby boomers
(born 1955-1964); and Gen Xers (born 1965-1974). The survey collected data every
two years on predisposing (e.g., sex, education), enabling (e.g., income),
behavior-related factors (e.g., obesity), need (e.g., chronic conditions), and
use of conventional care (primary care and specialists). RESULTS: The findings
suggest that, at corresponding ages, more recent cohorts reported greater CAM (OR
= 25.9, 95% CI: 20.0; 33.6 for Gen Xers vs. pre-World War) and chiropractic use
than their predecessors (OR = 2.2, 95% CI: 1.7; 2.8 for Gen Xers vs. pre-World
War). There was also a secular trend of increasing CAM use, but not chiropractic
use, over time (period effect) across all ages. Factors associated with cohort
differences were different for CAM and chiropractic use. Cohort differences in
CAM use were partially related to a period effect of increasing CAM use over time
across all ages while cohort differences in chiropractic use were related to the
higher prevalence of chronic conditions among recent cohorts. The use of
conventional care was positively related to greater CAM use (OR = 1.8, 95% CI:
1.6; 2.0) and chiropractic use (OR = 1.2, 95% CI: 1.1; 1.4) but did not
contribute to changes over time or to cohort differences in CAM and chiropractic
use. CONCLUSION: The higher CAM use over time and in recent cohorts could reflect
how recent generations are approaching their healthcare needs by expanding
conventional care to include CAM therapies and practice for treatment and health
promotion. The findings also underscore the importance of doctors discussing CAM
use with their patients.
PMID- 28494012
TI - Fabrication of malleable three-dimensional-printed customized bolus using three
dimensional scanner.
AB - A three-dimensional (3D)-printed customized bolus (3D bolus) can be used for
radiotherapy application to irregular surfaces. However, bolus fabrication based
on computed tomography (CT) scans is complicated and also delivers unwanted
irradiation. Consequently, we fabricated a bolus using a 3D scanner and evaluated
its efficacy. The head of an Alderson Rando phantom was scanned with a 3D
scanner. The 3D surface data were exported and reconstructed with Geomagic Design
X software. A 3D bolus of 5-mm thickness designed to fit onto the nose was
printed with the use of rubber-like printing material, and a radiotherapy plan
was developed. We successfully fabricated the customized 3D bolus, and further, a
CT simulation indicated an acceptable fit of the 3D bolus to the nose. There was
no air gap between the bolus and the phantom surface. The percent depth dose
(PDD) curve of the phantom with the 3D bolus showed an enhanced surface dose when
compared with that of the phantom without the bolus. The PDD of the 3D bolus was
comparable with that of a commercial superflab bolus. The radiotherapy plan
considering the 3D bolus showed improved target coverage when compared with that
without the bolus. Thus, we successfully fabricated a customized 3D bolus for an
irregular surface using a 3D scanner instead of a CT scanner.
PMID- 28494013
TI - Modeling spatial variation in risk of presence and insecticide resistance for
malaria vectors in Laos.
AB - Climatic, sociological and environmental conditions are known to affect the
spatial distribution of malaria vectors and disease transmission. Intensive use
of insecticides in the agricultural and public health sectors exerts a strong
selective pressure on resistance genes in malaria vectors. Spatio-temporal models
of favorable conditions for Anopheles species' presence were developed to
estimate the probability of presence of malaria vectors and insecticide
resistance in Lao PDR. These models were based on environmental and
meteorological conditions, and demographic factors. GIS software was used to
build and manage a spatial database with data collected from various geographic
information providers. GIS was also used to build and run the models. Results
showed that potential insecticide use and therefore the probability of resistance
to insecticide is greater in the southwestern part of the country, specifically
in Champasack province and where malaria incidence is already known to be high.
These findings can help national authorities to implement targeted and effective
vector control strategies for malaria prevention and elimination among
populations most at risk. Results can also be used to focus the insecticide
resistance surveillance in Anopheles mosquito populations in more restricted
area, reducing the area of surveys, and making the implementation of surveillance
system for Anopheles mosquito insecticide resistance possible.
PMID- 28494014
TI - Singularity: Scientific containers for mobility of compute.
AB - Here we present Singularity, software developed to bring containers and
reproducibility to scientific computing. Using Singularity containers, developers
can work in reproducible environments of their choosing and design, and these
complete environments can easily be copied and executed on other platforms.
Singularity is an open source initiative that harnesses the expertise of system
and software engineers and researchers alike, and integrates seamlessly into
common workflows for both of these groups. As its primary use case, Singularity
brings mobility of computing to both users and HPC centers, providing a secure
means to capture and distribute software and compute environments. This ability
to create and deploy reproducible environments across these centers, a previously
unmet need, makes Singularity a game changing development for computational
science.
PMID- 28494015
TI - Long non-coding RNA Lethe regulates hyperglycemia-induced reactive oxygen species
production in macrophages.
AB - Type 2 diabetes mellitus is a complex, systemic metabolic disease characterized
by insulin resistance and resulting hyperglycemia, which is associated with
impaired wound healing. The clinical complications associated with hyperglycemia
are attributed, in part, to the increased production of reactive oxygen species
(ROS). Recent studies revealed that long non-coding RNAs (lncRNAs) play important
regulatory roles in many biological processes. Specifically, lncRNA Lethe has
been described as exhibiting an anti-inflammatory effect by binding to the p65
subunit of NFkappaB and blocking its binding to DNA and the subsequent activation
of downstream genes. We therefore hypothesize that dysregulation of Lethe's
expression plays a role in hyperglycemia-induced ROS production. To test our
hypothesis, we treated RAW264.7 macrophages with low glucose (5 mM) or high
glucose (25 mM) for 24h. High glucose conditions significantly induced ROS
production and NOX2 gene expression in RAW cells, while significantly decreasing
Lethe gene expression. Overexpression of Lethe in RAW cells eliminated the
increased ROS production induced by high glucose conditions, while also
attenuating the upregulation of NOX2 expression. Similar results was found also
in non-diabetic and diabetic primary macrophage, bone marrow derived macrophage
(BMM). Furthermore, overexpression of Lethe in RAW cells treated with high
glucose significantly reduced the translocation of p65-NFkB to the nucleus, which
resulted in decreased NOX2 expression and ROS production. Interestingly, these
findings are consistent with the decreased Lethe gene expression and increased
NOX2 gene expression observed in a mouse model of diabetic wound healing. These
findings provide the first evidence that lncRNA Lethe is involved in the
regulation of ROS production in macrophages through modulation of NOX2 gene
expression via NFkappaB signaling. Moreover, this is the first report to describe
a role of lncRNAs, in particular Lethe, in impaired diabetic wound healing.
Further studies are warranted to determine if correction of Lethe expression in
diabetic wounds could improve healing.
PMID- 28494016
TI - The host ubiquitin-dependent segregase VCP/p97 is required for the onset of human
cytomegalovirus replication.
AB - The human cytomegalovirus major immediate early proteins IE1 and IE2 are critical
drivers of virus replication and are considered pivotal in determining the
balance between productive and latent infection. IE1 and IE2 are derived from the
same primary transcript by alternative splicing and regulation of their
expression likely involves a complex interplay between cellular and viral
factors. Here we show that knockdown of the host ubiquitin-dependent segregase
VCP/p97, results in loss of IE2 expression, subsequent suppression of early and
late gene expression and, ultimately, failure in virus replication. RNAseq
analysis showed increased levels of IE1 splicing, with a corresponding decrease
in IE2 splicing following VCP knockdown. Global analysis of viral transcription
showed the expression of a subset of viral genes is not reduced despite the loss
of IE2 expression, including UL112/113. Furthermore, Immunofluorescence studies
demonstrated that VCP strongly colocalised with the viral replication
compartments in the nucleus. Finally, we show that NMS-873, a small molecule
inhibitor of VCP, is a potent HCMV antiviral with potential as a novel host
targeting therapeutic for HCMV infection.
PMID- 28494017
TI - Distinct cellular toxicity of two mutant huntingtin mRNA variants due to
translation regulation.
AB - Huntington's disease (HD) is a neurodegenerative disorder caused by CAG repeat
expansion within exon1 of the HTT gene. The gene generates two mRNA variants that
carry either a short or long 3' untranslated region (3'UTR) while encoding the
same protein. It remains unknown whether the two mRNA variants play distinct
roles in HD pathogenesis. We found that the long HTT 3'UTR was capable of guiding
mRNA to neuronal dendrites, suggesting that some long-form HTT mRNA is
transported to dendrites for local protein synthesis. To assay roles of two HTT
mRNA variants in cell bodies, we expressed mRNA harboring HTT exon1 containing
23x or 145x CAGs with the short or long 3'UTR. We found that mutant mRNA
containing the short 3'UTR produced more protein aggregates and caused more
apoptosis in both cultured neurons and HEK293 cells, compared with mutant mRNA
containing the long 3'UTR. Although the two 3'UTRs did not affect mRNA stability,
we detected higher levels of protein synthesis from mRNA containing the short
3'UTR than from mRNA containing the long 3'UTR. These results indicate that the
long HTT 3'UTR suppresses translation. Thus, short-form mutant HTT mRNA will be
more efficient in producing toxic protein than its long-form counterpart.
PMID- 28494018
TI - Pathogenic outcome following experimental infection of sheep with Chlamydia
abortus variant strains LLG and POS.
AB - This study investigated the pathogenesis of two variant strains (LLG and POS) of
Chlamydia abortus, in comparison to a typical wild-type strain (S26/3) which is
known to be responsible for late term abortion in small ruminants. Challenge with
the three strains at mid-gestation resulted in similar pregnancy outcomes, with
abortion occurring in approximately 50-60% of ewes with the mean gestational
lengths also being similar. However, differences were observed in the severity of
placental pathology, with infection appearing milder for strain LLG, which was
reflected in the lower number of organisms shed in vaginal swabs post-partum and
less gross pathology and organisms present in placental smears. Results for
strain POS were somewhat different than LLG with a more focal restriction of
infection observed. Post-abortion antibody responses revealed prominent
differences in seropositivity to the major outer membrane protein (MOMP) present
in elementary body (EB) preparations under denaturing conditions, most notably
with anti-LLG and anti-POS convalescent sera where there was no or reduced
detection of MOMP present in EBs derived from the three strains. These results
and additional analysis of whole EB and chlamydial outer membrane complex
preparations suggest that there are conformational differences in MOMP for the
three strains. Overall, the results suggest that gross placental pathology and
clinical outcome is not indicative of bacterial colonization and the severity of
infection. The results also highlight potential conformational differences in
MOMP epitopes that perhaps impact on disease diagnosis and the development of new
vaccines.
PMID- 28494019
TI - The issue of plasma asymmetric dimethylarginine reference range - A systematic
review and meta-analysis.
AB - BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of
nitric oxide synthase, marker and mediator of endothelial dysfunction. Several
studies have demonstrated its value in cardiovascular risk stratification and all
cause mortality prediction. The aim was to determine the reference range of
plasma ADMA in healthy adults. METHODS AND RESULTS: Taking into account the most
widely used ADMA measurement methods, only studies using either high performance
liquid chromatography (HPLC) -with fluorescence or mass spectrometric detection-,
or enzyme-linked immunosorbent assay (ELISA) to quantify plasma ADMA
concentrations were enrolled. 66 studies were included in the quantitative
analysis (24 using ELISA and 42 using HPLC) reporting a total number of 5528 non
diabetic, non-hypertensive, non-obese adults without any medication (3178 men and
2350 women, 41.6 +/- 16.9 years old). The reference range of ADMA (in MUmol/l
with 95% confidence interval in parenthesis) was 0.34 (0.29-0.38)- 1.10 (0.85
1.35) with a mean of 0.71 (0.57-0.85) (n = 4093) measured by HPLC and 0.25 (0.18
0.31)- 0.92 (0.76-1.09) with a mean of 0.57 (0.48-0.66) (n = 1435) by ELISA.
CONCLUSIONS: Numerous publications suggested that asymmetric dimethylarginine is
not only an outstanding tool of disease outcome prediction but also a new
potential therapeutic target substance; the reference range provided by this meta
analysis can become of great importance and aid to further investigations.
However, developing a standard measurement method would be beneficial to
facilitate the clinical usage of ADMA.
PMID- 28494020
TI - Pannexin 3 regulates proliferation and differentiation of odontoblasts via its
hemichannel activities.
AB - Highly coordinated regulation of cell proliferation and differentiation
contributes to the formation of functionally shaped and sized teeth; however, the
mechanism underlying the switch from cell cycle exit to cell differentiation
during odontogenesis is poorly understood. Recently, we identified pannexin 3
(Panx3) as a member of the pannexin gap junction protein family from tooth germs.
The expression of Panx3 was predominately localized in preodontoblasts that arise
from dental papilla cells and can differentiate into dentin-secreting
odontoblasts. Panx3 also co-localized with p21, a cyclin-dependent kinase
inhibitor protein, in preodontoblasts. Panx3 was expressed in primary dental
mesenchymal cells and in the mDP dental mesenchymal cell line. Both Panx3 and p21
were induced during the differentiation of mDP cells. Overexpression of Panx3 in
mDP cells reduced cell proliferation via up-regulation of p21, but not of p27,
and promoted the Bone morphogenetic protein 2 (BMP2)-induced phosphorylation of
Smad1/5/8 and the expression of dentin sialophosphoprotein (Dspp), a marker of
differentiated odontoblasts. Furthermore, Panx3 released intracellular ATP into
the extracellular space through its hemichannel and induced the phosphorylation
of AMP-activated protein kinase (AMPK). 5-Aminoimidazole-4-carboxamide
ribonucleoside (AICAR), an activator of AMPK, reduced mDP cell proliferation and
induced p21 expression. Conversely, knockdown of endogenous Panx3 by siRNA
inhibited AMPK phosphorylation, p21 expression, and the phosphorylation of
Smad1/5/8 even in the presence of BMP2. Taken together, our results suggest that
Panx3 modulates intracellular ATP levels, resulting in the inhibition of
odontoblast proliferation through the AMPK/p21 signaling pathway and promotion of
cell differentiation by the BMP/Smad signaling pathway.
PMID- 28494021
TI - Rice black streaked dwarf virus P7-2 forms a SCF complex through binding to Oryza
sativa SKP1-like proteins, and interacts with GID2 involved in the gibberellin
pathway.
AB - As a core subunit of the SCF complex that promotes protein degradation through
the 26S proteasome, S-phase kinase-associated protein 1 (SKP1) plays important
roles in multiple cellular processes in eukaryotes, including gibberellin (GA),
jasmonate, ethylene, auxin and light responses. P7-2 encoded by Rice black
streaked dwarf virus (RBSDV), a devastating viral pathogen that causes severe
symptoms in infected plants, interacts with SKP1 from different plants. However,
whether RBSDV P7-2 forms a SCF complex and targets host proteins is poorly
understood. In this study, we conducted yeast two-hybrid assays to further
explore the interactions between P7-2 and 25 type I Oryza sativa SKP1-like (OSK)
proteins, and found that P7-2 interacted with eight OSK members with different
binding affinity. Co-immunoprecipitation assay further confirmed the interaction
of P7-2 with OSK1, OSK5 and OSK20. It was also shown that P7-2, together with
OSK1 and O. sativa Cullin-1, was able to form the SCF complex. Moreover, yeast
two-hybrid assays revealed that P7-2 interacted with gibberellin insensitive
dwarf2 (GID2) from rice and maize plants, which is essential for regulating the
GA signaling pathway. It was further demonstrated that the N-terminal region of
P7-2 was necessary for the interaction with GID2. Overall, these results
indicated that P7-2 functioned as a component of the SCF complex in rice, and
interaction of P7-2 with GID2 implied possible roles of the GA signaling pathway
during RBSDV infection.
PMID- 28494022
TI - The effect of biological sealants and adhesive treatments on matrix
metalloproteinase expression during renal injury healing.
AB - BACKGROUND: Renal injuries are relatively common in cases of abdominal trauma.
Adhesives and sealants can be used to repair and preserve damaged organs. Using a
rat model, this study explores the activity of different matrix
metalloproteinases (MMP) during the healing of renal injuries treated by two
biological adhesives (TachoSil and GelitaSpon) and a new synthetic elastic
cyanoacrylate (Adhflex). METHODS: Renal traumatic injuries were experimentally
induced in 90 male Wistar rats by a Stiefel Biopsy Punch in the anterior aspect
of the left kidney. Animals were divided into five groups: 1, sham non-injured (n
= 3); 2, non-treated standard punch injury (n = 6); 3, punch injury treated with
TachoSil (n = 27); 4, punch injury treated with GelitaSpon (n = 27); and, 5,
punch injury treated with Adhflex (n = 27). Wound healing was evaluated 2, 6, and
18 days after injury by determining the expression of MMPs, and the
histopathological evolution of lesions. FINDINGS: Histologically, the wound size
at 6 days post-injury was larger in Adhflex-treated samples than in the other
treatments, but the scarring tissue was similar at 18 days post-injury. Only the
MMPs subtypes 1, 2, 8, 9, and 13 were sufficiently expressed to be quantifiable.
Both time since injury and treatment type had a significant influence on MMPs
expression. Two days after injury, the expression of MMP8 and MMP9 was
predominant. MMP2 expression was greater 6 days after injury. The Adhflex-treated
group had a significantly higher MMPs expression than the other treatment groups
at all healing stages. CONCLUSIONS: All three sealant treatments induced almost
similar expression of MMPs than untreated animals indicating a physiological
healing process. Given that all renal trauma injuries must be considered
emergencies, both biological and synthetic adhesives, such as Adhflex, should be
considered as a treatment options.
PMID- 28494023
TI - Your move: The effect of chess on mathematics test scores.
AB - We analyse the effect of substituting a weekly mathematics lesson in primary
school grades 1-3 with a lesson in mathematics based on chess instruction. We use
data from the City of Aarhus in Denmark, combining test score data with a
comprehensive data set obtained from administrative registers. We use two
different methodological approaches to identify and estimate treatment effects
and we tend to find positive effects, indicating that knowledge acquired through
chess play can be transferred to the domain of mathematics. We also find larger
impacts for unhappy children and children who are bored in school, perhaps
because chess instruction facilitates learning by providing an alternative
approach to mathematics for these children. The results are encouraging and
suggest that chess may be an important and effective tool for improving
mathematical capacity in young students.
PMID- 28494024
TI - Household food security and adequacy of child diet in the food insecure region
north in Ghana.
AB - BACKGROUND AND OBJECTIVES: Adequate diet is of crucial importance for healthy
child development. In food insecure areas of the world, the provision of adequate
child diet is threatened in the many households that sometimes experience having
no food at all to eat (household food insecurity). In the context of food
insecure northern Ghana, this study investigated the relationship between level
of household food security and achievement of recommended child diet as measured
by WHO Infant and Young Child Feeding Indicators. METHODS: Using data from
households and 6-23 month old children in the 2012 Feed the Future baseline
survey (n = 871), descriptive analyses assessed the prevalence of minimum meal
frequency; minimum dietary diversity, and minimum acceptable diet. Logistic
regression analysis was used to examine the association of minimum acceptable
diet with household food security, while accounting for the effects of child sex
and age, maternal -age, -dietary diversity, -literacy and -education, household
size, region, and urban-rural setting. Household food security was assessed with
the Household Hunger Scale developed by USAID's Food and Nutrition Technical
Assistance Project. RESULTS: Forty-nine percent of children received minimum
recommended meal frequency, 31% received minimum dietary diversity, and 17% of
the children received minimum acceptable diet. Sixty-four percent of the children
lived in food secure households, and they were significantly more likely than
children in food insecure households to receive recommended minimum acceptable
diet [O.R = 0.53; 95% CI: 0.35, 0.82]. However, in 80% of food secure households,
children did not receive a minimal acceptable diet by WHO standards. CONCLUSIONS:
Children living in food secure households were more likely than others to receive
a minimum acceptable diet. Yet living in a food secure household was no guarantee
of child dietary adequacy, since eight of 10 children in food secure households
received less than a minimum acceptable diet. The results call for research into
factors besides household food security in the search for determinants of child
diet adequacy. In this study at least, household food security was a very weak
marker of child diet adequacy. This finding is of significance to public health
practice, since it calls into question any assumption that having enough food in
a household necessarily results in adequately fed children.
PMID- 28494026
TI - Correction: Role of Interleukin-10 on Nasal Polypogenesis in Patients with
Chronic Rhinosinusitis with Nasal Polyps.
AB - [This corrects the article DOI: 10.1371/journal.pone.0161013.].
PMID- 28494025
TI - Sequencing of small RNAs of the fern Pleopeltis minima (Polypodiaceae) offers
insight into the evolution of the microrna repertoire in land plants.
AB - MicroRNAs (miRNAs) are short, single stranded RNA molecules that regulate the
stability and translation of messenger RNAs in diverse eukaryotic groups. Several
miRNA genes are of ancient origin and have been maintained in the genomes of
animal and plant taxa for hundreds of millions of years, playing key roles in
development and physiology. In the last decade, genome and small RNA (sRNA)
sequencing of several plant species have helped unveil the evolutionary history
of land plants. Among these, the fern group (monilophytes) occupies a key
phylogenetic position, as it represents the closest extant cousin taxon of seed
plants, i.e. gymno- and angiosperms. However, in spite of their evolutionary,
economic and ecological importance, no fern genome has been sequenced yet and few
genomic resources are available for this group. Here, we sequenced the small RNA
fraction of an epiphytic South American fern, Pleopeltis minima (Polypodiaceae),
and compared it to plant miRNA databases, allowing for the identification of
miRNA families that are shared by all land plants, shared by all vascular plants
(tracheophytes) or shared by euphyllophytes (ferns and seed plants) only. Using
the recently described transcriptome of another fern, Lygodium japonicum, we also
estimated the degree of conservation of fern miRNA targets in relation to other
plant groups. Our results pinpoint the origin of several miRNA families in the
land plant evolutionary tree with more precision and are a resource for future
genomic and functional studies of fern miRNAs.
PMID- 28494027
TI - No evidence of genome editing activity from Natronobacterium gregoryi Argonaute
(NgAgo) in human cells.
AB - The argonaute protein from the thermophilic bacterium Thermus thermophilus shows
DNA-guided DNA interfering activity at high temperatures, complicating its
application in mammalian cells. A recent work reported that the argonaute protein
from Natronobacterium gregoryi (NgAgo) had DNA-guided genome editing activity in
mammalian cells. We compared the genome editing activities of NgAgo and
Staphylococcus aureus Cas9 (SaCas9) in human HEK293T cells side by side. EGFP
reporter assays and DNA sequencing consistently revealed high genome editing
activity from SaCas9. However, these assays did not demonstrate genome editing
activity by NgAgo. We confirmed that the conditions allowed simultaneous
transfection of the NgAgo expressing plasmid DNA and DNA guides, as well as
heterologous expression of NgAgo in the HEK293T cells. Our data show that NgAgo
is not a robust genome editing tool, although it may have such activity under
other conditions.
PMID- 28494028
TI - Rosemary supplementation (Rosmarinus oficinallis L.) attenuates cardiac
remodeling after myocardial infarction in rats.
AB - BACKGROUND: Myocardial infarction (MI) is one of the leading causes of morbidity
and mortality worldwide. Dietary intervention on adverse cardiac remodeling after
MI has significant clinical relevance. Rosemary leaves are a natural product with
antioxidant/anti-inflammatory properties, but its effect on morphology and
ventricular function after MI is unknown. METHODS AND RESULTS: To determine the
effect of the dietary supplementation of rosemary leaves on cardiac remodeling
after MI, male Wistar rats were divided into 6 groups after sham procedure or
experimental induced MI: 1) Sham group fed standard chow (SR0, n = 23); 2) Sham
group fed standard chow supplemented with 0.02% rosemary (R002) (SR002, n = 23);
3) Sham group fed standard chow supplemented with 0.2% rosemary (R02) (SR02, n =
22); 4) group submitted to MI and fed standard chow (IR0, n = 13); 5) group
submitted to MI and fed standard chow supplemented with R002 (IR002, n = 8); and
6) group submitted to MI and fed standard chow supplemented with R02 (IR02, n =
9). After 3 months of the treatment, systolic pressure evaluation,
echocardiography and euthanasia were performed. Left ventricular samples were
evaluated for: fibrosis, cytokine levels, apoptosis, energy metabolism enzymes,
and oxidative stress. Rosemary dietary supplementation attenuated cardiac
remodeling by improving energy metabolism and decreasing oxidative stress.
Rosemary supplementation of 0.02% improved diastolic function and reduced
hypertrophy after MI. Regarding rosemary dose, 0.02% and 0.2% for rats are
equivalent to 11 mg and 110 mg for humans, respectively. CONCLUSION: Our findings
support further investigations of the rosemary use as adjuvant therapy in adverse
cardiac remodeling.
PMID- 28494030
TI - Antibody-nanoparticle conjugates to enhance the sensitivity of ELISA-based
detection methods.
AB - Accurate antigen detection is imperative for clinicians to diagnose disease,
assess treatment success, and predict patient prognosis. The most common
technique used for the detection of disease-associated biomarkers is the enzyme
linked immunosorbent assay (ELISA). In an ELISA, primary antibodies are incubated
with biological samples containing the biomarker of interest. Then, detectible
secondary antibodies conjugated with horseradish peroxidase (HRP) bind the
primary antibodies. Upon addition of a color-changing substrate, the samples
provide a colorimetric signal that directly correlates to the targeted biomarker
concentration. While ELISAs are effective for analyzing samples with high
biomarker content, they lack the sensitivity required to analyze samples with low
antigen levels. We hypothesized that the sensitivity of ELISAs could be enhanced
by replacing freely delivered primary antibodies with antibody-nanoparticle
conjugates that provide excess binding sites for detectible secondary antibodies,
ultimately leading to increased signal. Here, we investigated the use of
nanoshells (NS) decorated with antibodies specific to epidermal growth factor
receptor (EGFR) as a model system (EGFR-NS). We incubated one healthy and two
breast cancer cell lines, each expressing different levels of EGFR, with EGFR-NS,
untargeted NS, or unconjugated EGFR antibodies, as well as detectable secondary
antibodies. We found that EGFR-NS consistently increased signal intensity
relative to unconjugated EGFR antibodies, with a substantial 13-fold enhancement
from cells expressing high levels of EGFR. Additionally, 40x more unconjugated
antibodies were required to detect EGFR compared to those conjugated to NS. Our
results demonstrate that antibody-nanoparticle conjugates lower the detection
limit of traditional ELISAs and support further investigation of this strategy
with other antibodies and nanoparticles. Owing to their enhanced sensitivity, we
anticipate that nanoparticle-modified ELISAs can be used to detect low levels of
biomarkers found in various diseases, such as cancers, tuberculosis, and
rheumatoid arthritis, and may ultimately enable earlier diagnosis, better
prognostication, and improved treatment monitoring.
PMID- 28494029
TI - Characterization of miR-122-independent propagation of HCV.
AB - miR-122, a liver-specific microRNA, is one of the determinants for liver tropism
of hepatitis C virus (HCV) infection. Although miR-122 is required for efficient
propagation of HCV, we have previously shown that HCV replicates at a low rate in
miR-122-deficient cells, suggesting that HCV-RNA is capable of propagating in an
miR-122-independent manner. We herein investigated the roles of miR-122 in both
the replication of HCV-RNA and the production of infectious particles by using
miR-122-knockout Huh7 (Huh7-122KO) cells. A slight increase of intracellular HCV
RNA levels and infectious titers in the culture supernatants was observed in Huh7
122KO cells upon infection with HCV. Moreover, after serial passages of HCV in
miR-122-knockout Huh7.5.1 cells, we obtained an adaptive mutant, HCV122KO,
possessing G28A substitution in the 5'UTR of the HCV genotype 2a JFH1 genome, and
this mutant may help to enhance replication complex formation, a possibility
supported by polysome analysis. We also found the introduction of adaptive
mutation around miR-122 binding site in the genotype 1b/2a chimeric virus, which
originally had an adenine at the nucleotide position 29. HCV122KO exhibited
efficient RNA replication in miR-122-knockout cells and non-hepatic cells without
exogenous expression of miR-122. Competition assay revealed that the G28A mutant
was dominant in the absence of miR-122, but its effects were equivalent to those
of the wild type in the presence of miR-122, suggesting that the G28A mutation
does not confer an advantage for propagation in miR-122-rich hepatocytes. These
observations may explain the clinical finding that the positive rate of G28A
mutation was higher in miR-122-deficient PBMCs than in the patient serum, which
mainly included the hepatocyte-derived virus from HCV-genotype-2a patients. These
results suggest that the emergence of HCV mutants that can propagate in non
hepatic cells in an miR-122-independent manner may participate in the induction
of extrahepatic manifestations in chronic hepatitis C patients.
PMID- 28494031
TI - Evaluation of Pink and White Esthetic Scores for Immediately Placed and
Provisionally Restored Implants in the Anterior Maxilla.
AB - PURPOSE: To evaluate the esthetic result of immediately placed implants with
immediate provisional restorations in the anterior maxilla using the pink
esthetic score (PES) and white esthetic score (WES). MATERIALS AND METHODS: The
records of patients were evaluated retrospectively. The evaluation was carried
out by two examiners using 12 evaluation criteria. RESULTS: The average PES value
from the evaluation of 53 images obtained from the 53 selected patients (22 men
and 31 women) was 8.63 +/- 2.4 (range, 1-14), whereas the average WES value was
6.92 +/- 1.67 (range, 2-10). The mesial papilla had the highest average PES (1.39
+/- 0.4) and the distal papilla had the lowest PES (0.87 +/- 0.54). Texture had
the highest average WES (1.54 +/- 0.34) and tooth shape had the lowest average
WES (1.25 +/- 0.43). CONCLUSION: Treatment with immediate implants providing
immediate provisional restoration in the anterior maxilla yields good clinical
esthetic outcomes, as assessed by PES/WES values. The PES and WES values showed
strong intraexaminer agreement, but weak interexaminer agreement.
PMID- 28494032
TI - Radiographic Appearance of Interocclusal Record Materials for Cone Beam Computed
Tomography-Guided Implant Surgeries.
AB - PURPOSE: To select an ideal interocclusal record material for cone beam computed
tomography (CBCT)-guided implant surgery based on the material's radiodensity on
the scan. MATERIALS AND METHODS: Twelve commonly used interocclusal record
materials were used for this investigation: two were waxes, one was polyether,
and nine were polyvinyl-siloxane-type materials. A scan template was fabricated
by duplicating existing dentures in Ortho-Jet acrylic resin mixed with 30% barium
powder for the teeth and 10% barium powder for the denture base between the teeth
and the tissue. An interocclusal record was fabricated with each material, and
the same template was used to obtain a CBCT scan with an ICAT machine (Imaging
Sciences International) at 0.3 voxel and 14-bit depth settings. Twelve CBCT scans
were obtained and analyzed. The radiopacity of the barium teeth was used as a
control and was compared with the opacity of the 12 materials using a paired t
test. A post hoc analysis of variance (ANOVA) test was used to compare the
densities of the various materials with each other. RESULTS: There was a
statistically significant difference between the radiopacity of barium teeth
(gray value: 1,959.475) and that of Modelling Wax (gray value: 750; P = .0026),
Aluwax (gray value: 795.22; P = .0022), Blu-Bite CT (gray value: 1,105; P =
.005), Ramitec (gray value: 1,105.3; P = .08), Memosil 2 (gray value: 1,202; P =
.01) followed by Reprosil (gray value: 1,407.73; P = .01). Compared with the
barium teeth, there was no statistically significant difference between the
densities of Futar D (gray value: 1,866.5; P = .51), Jet Bite (gray value:
1,660.04; P = .08), Lab-Putty (gray value: 1,402.14; P = .19), and Memoreg 2
(gray value: 1,754.72; P = .1). The highest radiodensity was seen with Blu-Mousse
(gray value: 2,949; P = .007) and Take 1 (gray value: 2,229.85; P = .025), which
were also significantly different from the density of the barium teeth but in the
opposite direction, making them more opaque. CONCLUSION: Within the limitations
of this in vitro study, the most radiolucent appearance of Modelling Wax, Aluwax,
Memosil 2, Blu-Bite CT, and Ramitec made them the suitable materials of choice of
those tested, as the interocclusal registration record during CBCT scanning
allowed clear visualization of barium teeth.
PMID- 28494033
TI - Intraoperative Complications During Sinus Floor Elevation with Lateral Approach:
A Systematic Review.
AB - PURPOSE: To analyze the occurrence of intraoperative complications during sinus
floor elevation with a lateral approach and their correlations with the technique
adopted by surgeons. MATERIALS AND METHODS: Electronic and manual searches
resulted in 4,417 records on sinus floor elevation. Twenty-one randomized
clinical trials (RCTs) and 11 prospective controlled clinical trials (CCTs)
reporting occurrence of intraoperative complications were included. Risk of bias
was assessed according to the Cochrane tool and a modified Downs and Black
quality analysis for RCTs and CCTs, respectively. RESULTS: Sinus membrane
perforation and hemorrhagic events following vascular lesions were the only
intraoperative complications reported by the selected studies with overall
occurrences of 15.7% and 0.4%, respectively. Three different surgical devices
(rotary instruments, piezoelectric osteotomes, and manual bone scrapers) were
used to perform the lateral antrostomy. Ultrasonic devices and bone scrapers
showed a lower incidence (10.9% and 6.0%, respectively) of membrane perforation
compared with that of rotary instruments (20.1%). Among the different ultrasonic
procedures, erosion of the lateral antral wall showed the lowest membrane
perforations (4.7% incidence). Hemorrhagic complications seemed to be extremely
infrequent with any surgical technique. CONCLUSION: Sinus membrane perforation
was the most frequently described intraoperative complication during sinus floor
elevation with a lateral approach. Thinning the lateral wall of the sinus before
performing the antrostomy (either with ultrasonic devices or manual bone
scrapers) seemed to be an important factor in preventing membrane perforation
during sinus surgery. Further high-quality RCTs specifically investigating
intraoperative complication occurrence are needed.
PMID- 28494034
TI - Efficacy of Local and Systemic Statin Delivery on the Osseointegration of
Implants: A Systematic Review.
AB - PURPOSE: In indexed literature, a systematic review of the efficacy of statins in
enhancing osseointegration is lacking. The aim of this systematic review was to
assess the efficacy of local and systemic statin delivery on the osseointegration
of implants. MATERIALS AND METHODS: To address the focused question, "Does local
and systemic statin delivery affect osseointegration around implants?", indexed
databases were searched from 1965 through November 2015 using various keywords.
Letters to the Editor, case reports/case series, historic reviews, and
commentaries were excluded. The pattern of this systematic review was customized
to primarily summarize the pertinent data. RESULTS: Nineteen studies were
included. All studies were experimental and were performed in animal models. In
seven studies, statins were delivered systemically via oral, intraperitoneal,
intraosseous, subcutaneous, and percutaneous routes. Among the 12 studies, where
statins were delivered locally, statin-coated implants were used in seven
studies, whereas in the remaining studies, statins were delivered via topical
application on the bone cavities. The follow-up duration ranged between 1 and 12
weeks. Results from 18 studies showed that statin administration enhanced new
bone formation (NBF) around implants and/or bone-to-implant contact. One study
showed that statin-coated implant surfaces impaired osseointegration. Seven
studies reported that statin administration enhanced NBF around implants in
osteoporotic rats. CONCLUSION: On experimental grounds, local and systemic statin
delivery seems to enhance osseointegration; however, from a clinical perspective,
further studies are needed to assess the role of statins in promoting
osseointegration around dental implants.
PMID- 28494035
TI - An In Vitro Model to Evaluate the Accuracy of Guided Implant Placement Based on
the Surgeon's Experience.
AB - PURPOSE: To evaluate whether there are differences in the accuracy of guided
implant placement based on the surgeon's experience level. MATERIALS AND METHODS:
Fifteen surgeons, divided into three groups based on experience level (group I,
expert; group II, intermediate; group III, novice), placed six implants in five
identical mandibles (75 mandibles and 450 implants). A planning and
stereolithographic guide was generated using cone beam computed tomography (CBCT)
images and implant planning software (Nemoscan, Nemotec) and was used in all
cases. After the implants were placed in each mandible, another scan was taken,
and the three-dimensional (3D) images of each scan were blended with the images
in the planning guide to evaluate any deviations. Any differences in platform and
apex position and the angle of the implant were measured. The differences between
each surgeon and each group were compared using multivariate analysis of variance
(MANOVA). RESULTS: There were significant differences in the implant angles among
the three groups (P = .001). Group III (novices) presented the greatest angle
deviation and showed more deviations than group I (experts) (P = .024) and group
II (intermediate) (P = .001) did. There were no significant differences between
groups I and II (P = .368). There were no significant differences among the
groups in terms of platform (P = .135) and apex position (P = .092). CONCLUSION:
Some degree of deviation can occur between the planned placement of the implant
and its definitive placement, and this deviation may be influenced by the
surgeon's experience. Expert surgeons show less angle deviation than novice
surgeons. Although these differences (less than 0.5 degrees) are statistically
significant, they may be considered clinically irrelevant.
PMID- 28494036
TI - Epidemiology of Implant Mortality Disparity Among Intraoral Positions and
Prosthesis Types.
AB - PURPOSE: To examine the disparity of single-crown implant failure with a similar
loss of the splinted prosthesis in differing anatomical locations while
controlling for other demographic and clinical variables that may confound the
relationship between prosthesis types and implant loss. MATERIALS AND METHODS: A
multicenter retrospective cohort study was designed to include patients treated
with dental implants from 2003 to 2014. The variables included age, sex, systemic
disease, bone graft, implant placement date, position of dental implant, length
of dental implant, diameter of dental implant, loading time, type of prosthesis,
type of opposing occlusion, latest check date, and survival or loss of the dental
implant. The demographic and clinical variables' influence on the survival of
dental implants was estimated by the Kaplan-Meier method. The position and
diameter were adjusted for the accurate estimation of the relationship between
the prosthesis type and survival of the dental implant with the Cox proportional
hazard method. RESULTS: A total of 1,151 dental implants from 403 patients were
ascertained. After adjusting for the confounding effect of position and diameter,
single-crown prostheses were 38.1 (95% CI: 15.1-118) times more likely to be lost
than the connected-type prostheses. For single-crown implants, the waiting time
for osseointegration before loading was the highest for the maxillary molar
position and the lowest for the mandibular molar position (P < .0001), while the
most frequent implant loss occurred in the maxillary anterior area, and the
second frequent area was the maxillary molar position; the lowest occurrence of
implant loss was for the mandibular molar position. This disparity was
statistically significant (P = .0271). CONCLUSION: Despite the high survival
rates of endosseous implants as a whole, since the variation of implant loss was
observed among the different anatomical positions for single-crown implants,
special attention has to be given to the maxillary anterior and maxillary molar
positions. A longer healing time assuming compensation for disadvantageous bone
quality was not directly effective in increasing implant longevity in the
vulnerable positions.
PMID- 28494037
TI - Effect of Abutment Preparation and Fatigue Loading in a Moist Environment on the
Fracture Resistance of the One-Piece Zirconia Dental Implant.
AB - PURPOSE: One-piece zirconia dental implants have been widely used in Europe for
many years. This in vitro study was done to evaluate the effect of abutment
preparation and fatigue (cyclic) loading in a moist environment on the fracture
resistance of the one-piece zirconia dental implant. MATERIALS AND METHODS:
Twenty-four Cera Root zirconium oxide dental implants, divided into three groups
of eight, were used in this study: group 1 (control group): implants with no
preparation, tested in a dry environment; group 2: implants with no preparation,
tested in a moist environment (simulating clinical conditions); and group 3:
implants after abutment preparation tested in a moist environment. All implants
received IPS e.max porcelain crowns. All samples were subjected to nearly 1
million cycles of sinusoidal fatigue loading (-10 N to -200 N) in a universal
testing machine. The postfatigue samples were loaded to fracture. Significant
differences (alpha = .05) in mean fracture loads were statistically analyzed.
RESULTS: There was no catastrophic failure of any of the implants during the
fatigue tests. The mean (SD) of the fracture loads in postfatigue load-to-failure
tests were: group 1: 1,202.9 (62.6); group 2: 1,164.6 (73.8); and group 3: 953.5
(103). Analysis of variance (ANOVA) and post hoc Tukey-Kramer contrast revealed a
statistically significant difference (P < .05) between the mean fracture load of
group 3 and those of groups 1 and 2, but no significant difference (P > .05)
between groups 1 and 2. CONCLUSION: While there was a statistically significant
adverse effect of abutment preparation and fatigue loading in a moist environment
on the postfatigue implant failure load, the load-to-fracture mean of surface
prepared implants after fatigue tests was nevertheless significantly higher than
the mean fracture load of the crowns (P < .05) as well as the minimum load
bearing requirement (300 N) for anterior restorations. Abutment preparation in a
one-piece zirconia implant is therefore considered clinically safe and
acceptable.
PMID- 28494038
TI - Role of Metformin in Reversing the Negative Impact of Hyperglycemia on Bone
Healing Around Implants Inserted in Type 2 Diabetic Rats.
AB - PURPOSE: There is interest in establishing hypoglycemiant agents able to
contain/revert the impact of diabetes mellitus on osseointegration. The purpose
of this study was to assess the possible effect of metformin in reversing the
negative effects of hyperglycemia on the healing of bone surrounding implants
inserted in rats. MATERIALS AND METHODS: Rats (10 per group) were assigned to one
of the following groups: DM group: type 2 diabetic rats deprived of metformin (M)
treatment; MDM group: type 2 diabetic rats under M treatment (40 mg/kg/day,
starting on the 15th day after implant placement); control group: nondiabetic
rats without M treatment. At 30 days after streptozotocin injection, titanium
implants were placed in tibiae. Animals were euthanized 30 days after implant
surgery. Bone-to-implant contact (BIC), bone area (BA), and the number of
receptor activator of nuclear factor kappaB ligand (RANKL)- and osteoprotegerin
(OPG)-stained cells were assessed in cortical and medullary areas. RESULTS: The
percentages of BIC and BA in the cortical bone were reduced in the DM and MDM
groups compared with the control group (P < .05). The percentage of BA in the
medullary region was reduced in the DM group compared with the control group (P <
.05). The MDM group showed the greatest number of OPG-stained cells, while the DM
group presented the greatest ratio of RANKL/OPG in the medullary area (P < .05).
CONCLUSION: Metformin did not modulate the damaging effect of hyperglycemia on
bone healing around implants at histometric levels, but increased the expression
of OPG and decreased the RANKL/OPG ratio in the medullary area, yielding some
molecular benefits in the osseointegration of implants under the hyperglycemic
state.
PMID- 28494039
TI - Top-Cited Articles in Implant Dentistry.
AB - PURPOSE: Citation analysis is the field of bibliometrics that uses citation data
to evaluate the scientific recognition and the influential performance of a
research article in the scientific community. The aim of this study was to
conduct a bibliometric analysis of the top-cited articles pertaining to implant
dentistry, to analyze the main characteristics, and to display the most
interesting topics and evolutionary trends. MATERIALS AND METHODS: The 100 top
cited articles published in "Dentistry, Oral Surgery, and Medicine" journals were
identified using the Science Citation Index Database. The articles were further
reviewed, and basic information was collected, including the number of citations,
journals, authors, publication year, study design, level of evidence, and field
of study. RESULTS: The highly cited articles in implant dentistry were cited
between 199 and 2,229 times. The majority of them were published in four major
journals: Clinical Oral Implants Research, International Journal of Oral &
Maxillofacial Implants, Journal of Clinical Periodontology, and Journal of
Periodontology. The publication year ranged from 1981 to 2009, with 45% published
in a nine-year period (2001 to 2009). Publications from the United States (29%)
were the most heavily cited, followed by those from Sweden (23%) and Switzerland
(17%). The University of Goteborg from Sweden produced the highest number of
publications (n = 19), followed by the University of Bern in Switzerland (n =
13). There was a predominance of clinical papers (n = 42), followed by reviews (n
= 25), basic science research (n = 21), and proceedings papers (n = 12). Peri
implant tissue healing and health (24%), implant success/failures (19.2%), and
biomechanical topics (16.8%) were the most common fields of study. CONCLUSION:
Citation analysis in the field of implant dentistry reveals interesting
information about the topics and trends negotiated by researchers and elucidates
which characteristics are required for a paper to attain a "classic" status.
Clinical science articles published in high-impact specialized journals are most
likely to be cited in the field of implant dentistry.
PMID- 28494040
TI - Micro- to Macroroughness of Additively Manufactured Titanium Implants in Terms of
Coagulation and Contact Activation.
AB - PURPOSE: This study aimed to evaluate how as-built electron beam melting (EBM)
surface properties affect the onset of blood coagulation. The properties of EBM
manufactured implant surfaces for placement have, until now, remained largely
unexplored in literature. Implants with conventional designs and custom-made
implants have been manufactured using EBM technology and later placed into the
human body. Many of the conventional implants used today, such as dental
implants, display modified surfaces to optimize bone ingrowth, whereas custom
made implants, by and large, have machined surfaces. However, titanium in itself
demonstrates good material properties for the purpose of bone ingrowth. MATERIALS
AND METHODS: Specimens manufactured using EBM were selected according to their
surface roughness and process parameters. EBM-produced specimens, conventional
machined titanium surfaces, as well as PVC surfaces for control were evaluated
using the slide chamber model. RESULTS: A significant increase in activation was
found, in all factors evaluated, between the machined samples and EBM
manufactured samples. The results show that EBM-manufactured implants with as
built surfaces augment the thrombogenic properties. CONCLUSION: EBM that uses
Ti6Al4V powder appears to be a good manufacturing solution for load-bearing
implants with bone anchorage. The as-built surfaces can be used "as is" for
direct bone contact, although any surface treatment available for conventional
implants can be performed on EBM-manufactured implants with a conventional
design.
PMID- 28494041
TI - Innovative Single-Tooth Replacement with an Individual Root-Analog Hybrid Implant
in the Esthetic Zone: Case Report.
AB - The goal of this study was to explore an innovative approach to single-tooth
replacement using an individually custom-fabricated, root-analog, hybrid dental
implant, in the esthetic zone, to avoid the microgap and micromovements between
the implant and abutment. Moreover, the use of burs to prepare the implant
recipient site is not necessary in this technique, reducing the bone removal,
heating, and trauma. The process requires capturing accurate root geometry
through combined computer-aided design/computer-assisted manufacturing (CAD/CAM)
and a three-dimensional (3D) visualization (digital volume tomography [DVT]) of
the tooth in situ, which might result in reduced remodeling after insertion. A
good esthetic and functional outcome was obtained. The use of a root-shaped tooth
analog implant might be in selected cases a viable alternative to current
threaded cylindrical and cone-shaped implants. The new concept avoids the
microgap between the implant and the abutment and reduces the trauma to the
tissue and bone.
PMID- 28494042
TI - Three-Dimensional Implant Positioning with a Piezosurgery Implant Site
Preparation Technique and an Intraoral Surgical Navigation System: Case Report.
AB - This case report describes new implant site preparation techniques joining the
benefits of using an intraoral navigation system to optimize three-dimensional
implant site positioning in combination with an ultrasonic osteotomy. A report of
five patients is presented, and the implant positions as planned in the
navigation software with the postoperative scan image were compared. The
preliminary results are useful, although further clinical studies with larger
populations are needed to confirm these findings.
PMID- 28494043
TI - Maxillary Sinus Floor Augmentation Using Xenograft: Gene Expression and
Histologic Analysis.
AB - PURPOSE: Many histologic and histomorphometric studies as well as systematic
reviews have shown the clinical success of the use of anorganic bovine bone (ABB,
Bio-Oss) in maxillary sinus floor augmentation (MSFA). The molecular processes
involved in bone healing are, however, still unknown. The aims of this study were
to explore gene expression associated with bone remodeling and inflammation in
MSFA sites. MATERIALS AND METHODS: The mRNA expression levels of runt related
transcription factor 2 (RUNX2), receptor activator of NF-kB ligand (RANKL),
osteoprotegerin (OPG), matrix metallopeptidase 9 (MMP-9), tartrate-resistance
acid phosphatase (TRAP), and interleukin-1beta (IL-1beta), as well as the ratio
of RANKL/OPG were compared between alveolar bone of a group after MSFA with ABB
and a maxillary posterior edentulous bone group. Twenty-one bone samples were
collected at the time of implant placement after 6 months of MSFA or tooth
extraction. Fourteen bone samples from the MSFA group and from the maxillary
posterior edentulous bone without MSFA group were taken to analyze gene
expression by real-time reverse transcription polymerase chain reaction (RT-PCR).
Seven bone samples from the MSFA group were used for histologic analysis.
RESULTS: Real time RT-PCR revealed no statistically significant difference in
gene expression level of RUNX2, RANKL, OPG, MMP-9, TRAP, and IL-1beta, or in the
ratio of RANKL/OPG. Histology showed bone-lining cells at the edge and osteocyte
inside newly formed bone. Residual grafted particles were in close contact with
new bone. CONCLUSION: After a healing period of 6 months, ABB particles did not
have an effect on the expression of genes associated with bone remodeling and
inflammation. In addition, histologic evidence supports that ABB particles are
replaced by new bone formation and do not affect bone healing.
PMID- 28494044
TI - Placement of Zygomatic Implants into the Malar Prominence of the Maxillary Bone
for Apical Fixation: A Clinical Report of 5 to 13 Years.
AB - PURPOSE: This study was designed to evaluate long-term performance of zygomatic
implants using an alternative apical fixation point to establish the posterior
restorative foundation for fixed full-arch restoration. MATERIALS AND METHODS: A
retrospective study of all consecutively treated patients with advanced maxillary
resorption who were treated with zygomatic implants to support fixed prostheses
from August 14, 2001 through November 24, 2009 was conducted; the final follow-up
was August 31, 2015. All zygomatic implants were placed using the malar
prominence of the maxillary bone for apical fixation. Initial study casts were
analyzed to compute the anterior/posterior implant distribution, distance between
bilateral zygomatic implants, and variation from ideal zygomatic implant
positioning relative to the soft tissue crest. Soft tissue, implant, and
restorative complications also were recorded. RESULTS: Fifty-eight consecutively
treated patients with advanced maxillary resorption were included in the study-
18 men and 40 women, with a mean +/- SD age of 65.3 +/- 8.0 years and range of 49
to 85 years. Forty-nine patients received bilateral zygomatic implants placed
apically into the malar process of the maxillary bone, and nine patients received
similarly placed unilateral zygomatic implants with 107 zygomatic implants
reported. All patients had supplemental anterior implants and were restored with
a one-piece splint framework and fully implant-supported restoration. Follow-up
of 5 to 13 years was conducted, with a mean follow-up time of 8.4 years per
zygomatic implant. No losses of zygomatic implants occurred. No major surgical or
restorative complications were observed. CONCLUSION: Utilizing the malar
prominence of the maxilla for apical fixation of zygomatic implants predictably
allows prosthetic placement of the implant platform in a favorable first molar
position, eliminating prosthetic compromise.
PMID- 28494045
TI - Survival Analysis of Orbital Implants and Potential Influencing Factors: A
Retrospective Long-Term Study.
AB - PURPOSE: Application of endosseous implants in prosthetic orbital reconstruction
seems to be very successful, but few reports have evaluated cumulative survival
rates of orbital implants over a long period. The aim of this study was to
analyze long-term survival rates and potential influencing factors of orbital
implants. MATERIALS AND METHODS: A retrospective evaluation of patients treated
with extraoral screw implants for retaining orbital prostheses from 1991 to 2014
was performed. Patient records were assessed for implant survival, demographic
data, defect etiology, irradiation status, location of implant placement, implant
systems, length, and retention type. Data were analyzed using the Kaplan-Meier
method and log-rank test to compare survival curves. RESULTS: A total of 282
orbital implants placed in 78 patients were evaluated during an observation
period ranging from 2 to 268 months (mean: 94.97 months). The cumulative implant
survival rate was 91.3% at 2 years, 80.5% at 5 years, 68.7% at 10 years, and
62.2% after 15 years. The survival rate was significantly higher in females
(75.3%) vs males (47.3%), in supraorbital vs infraorbital implants (67.4% vs
51.5%), and in Branemark implants (70.2%) vs Straumann implants (54.5%).
CONCLUSION: The presented data suggest that the long-term predictability of
orbital implants revealed good to acceptable results. Factors such as female
gender, localization in the supraorbital rim, a machined surface of the implant
system, length, and magnetic retention seem to affect the implant survival rate
positively, whereas irradiation status does not show any influence. These factors
should be considered in planning future patient rehabilitation.
PMID- 28494047
TI - Comparison of Marginal Bone Level Changes of Immediately Loaded Implants, Delayed
Loaded Nonsubmerged Implants, and Delayed Loaded Submerged Implants: A Randomized
Clinical Trial.
AB - PURPOSE: The aim of this randomized clinical trial was to radiographically
compare peri-implant marginal bone level changes between immediately loaded
implants without the removal of an abutment placed at the time of surgery (IL),
delayed loaded nonsubmerged implants (NS), and delayed loaded submerged implants
(SI). MATERIALS AND METHODS: Patients' edentulous sites were randomly allocated
to the three groups of implants so that each patient received one implant of each
group. Digital periapical radiographs were obtained at baseline as well as three
(T1), six (T2), and nine (T3) months after implant insertion. The mesial and
distal bone crest levels adjacent to each implant were measured, and the mean
values were calculated for each implant at each period. The data were
statistically analyzed by repeated measures analysis of variance (ANOVA) and the
Tukey test (P < .05). RESULTS: The patient sample comprised 15 subjects (13 women
and 2 men; mean age: 47.7 years) with partially edentulous sites in the
mandibular posterior area. Forty-five implants were inserted (15 IL implants, 15
NS implants, and 15 SI implants). There was no statistically significant
difference between the three groups with regard to changes in the marginal bone
level during the follow-up period. The study achieved a 93.3% cumulative survival
rate for both delayed loaded groups (NS and IS) and a 100% survival rate for the
IL group. CONCLUSION: In the 9-month period following the implants, no
statistically significant differences were found between immediately and delayed
loaded implants or between submerged and nonsubmerged implants in bone level
changes in patients with partial posterior mandibular edentulism.
PMID- 28494046
TI - Traditional Postextractive Implant Site Preparation Compared with Pre-extractive
Interradicular Implant Bed Preparation in the Mandibular Molar Region, Using an
Ultrasonic Device: A Randomized Pilot Study.
AB - PURPOSE: The immediate placement of single postextractive implants is increasing
in the everyday clinical practice. Due to insufficient bone tissue volume, proper
primary stability, essential for subsequent osseointegration, is sometimes not
reached. The aim of this work was to compare two different approaches: implant
bed preparation before and after root extraction. MATERIALS AND METHODS: Twenty
two patients of both sexes were selected who needed an implant-prosthetic
rehabilitation of the fractured first mandibular molar or presented an
untreatable endodontic pathology. The sites were randomly assigned to the test
group (treated with implant bed preparation before molar extractions) or control
group (treated with implant bed preparation after molar extractions) by a
computer-generated table. All implants were placed by the same operator, who was
experienced in both traditional and ultrasonic techniques. The implant stability
quotient (ISQ) and the position of the implant were evaluated. Statistical
analysis was carried out. RESULTS: In the control group, three implants were
placed in the central portion of the bone septum, while eight implants were
placed with a tilted axis in relation to the septum; in the test group, all
implants were placed in ideal positions within the root extraction sockets. The
different position of the implants between the two procedures was statistically
significant. CONCLUSION: This work presented an innovative approach for implant
placement at the time of mandibular molar extraction. Preparing the implant bed
with an ultrasonic device before root extraction is a simple technique and also
allows greater stability to be reached in a selective case.
PMID- 28494048
TI - Satisfaction and Patient-Related Outcomes in 128 Patients with Single Implant
Crowns In Situ for up to 14 Years.
AB - PURPOSE: To assess patient satisfaction and patient-related outcomes across the
domains of appearance, cleansibility, and costs; the perceived value and worth
when single implant crowns (SICs) had been in situ up to 14 years; whether
satisfaction differed between patients; and whether certain characteristics might
affect the questionnaire response rate. MATERIALS AND METHODS: Patients treated
at a private prosthodontic practice between 2001 and 2014 (n = 207) who received
a SIC (n = 256) were prospectively included. A previously validated patient
satisfaction questionnaire (PSQ) exploring patient-centered outcomes was mailed
to participants. Demographic (sex, age) and treatment data (number of SICs, time
in situ, failure experience, complication experience) were collected. Visual
analog scale (VAS) responses were converted to percentages. Differences between
respondents and nonrespondents, differences in satisfaction between prosthesis
placement and survey date, and differences with respect to demographic and
treatment data were assessed. Averages were medians bounded by interquartile
ranges. Statistical significance was set at P = .05. RESULTS: Respondents (n =
128, 61.8%) and nonrespondents (n = 79, 38.2%) had similar demographic and
treatment characteristics. Prostheses had been in situ for up to 14 years
(median, 5 years; interquartile range [IQR], 24 to 96 months). Participants
reported that treatment met their expectations (median, 93%; IQR, 85% to 100%);
they reported high satisfaction with tooth color, tooth contour, peri-implant
mucosa, appearance overall, and ease of cleaning (medians ranging from 90.5% to
95%, IQR ranging from 80% to 100%) and medium satisfaction with costs when
prostheses were placed (median, 50%; IQR, 29% to 80%). Satisfaction with tooth
contour, peri-implant tissues, overall appearance, and costs significantly
improved over time (96%, 92.5%, 91.7%, and 75%, respectively; P < .001 to P =
.049). Levels of satisfaction did not differ by sex, number of implants,
survival, complications, number of complications, and time in situ. Younger
patients were less satisfied with the overall appearance and costs than older
patients (P = .004, P = .007, respectively). All patients would choose to undergo
treatment again and would recommend it to a friend. CONCLUSION: Patients with
SICs that were in situ up to 14 years who responded to the validated PSQ were
highly satisfied with the appearance and cleansibility, noted improvements in
peri-implant tissue contours, and found the treatment to be valuable and
worthwhile. They reported that upfront costs were high, but this concern
decreased when the SICs had been in the mouth for a period of time.
PMID- 28494049
TI - Assessment of Adhesion and Proliferation of Bone Marrow Mesenchymal Stem Cells in
Polymer Matrices with rhGH.
AB - PURPOSE: Biomaterials, as an alternative to autogenous bone and other biologic
tissues, have been widely used in oral and maxillofacial surgery. In this
context, a biomaterial that functions as a scaffold (osteoconductor), combined
with a growth factor (osteoinductor), would be of great interest for clinical
application. Biodegradable polymers used for slow drug release have been
investigated, demonstrating good results and interesting potential. Growth
hormone (GH) may be released by incorporating it into these polymers. This study
aimed to evaluate cell adhesion and proliferation of a polymeric biomaterial for
slow release of recombinant human GH (rhGH). MATERIALS AND METHODS: Poly(lactic
co-glycolic acid) (PLGA) and PLGA/polycaprolactone (PCL) (at a 70/30 ratio of
PLGA to PCL) matrices were prepared by the solvent evaporation method, combined
or not with GH. Biomaterials were tested for cell adhesion and proliferation by
culture in mesenchymal stem cells derived from Wistar rat bone marrow, 4',6
diamidino-2-phenylindole (DAPI) staining, and subsequent cell counting, in
addition to scanning electron microscopy. Cell adhesion and proliferation was
assessed at 24 and 72 hours of biomaterial exposure to culture medium. RESULTS:
All tested polymers exhibited cell adhesion and proliferation. However, PLGA
based biomaterials, especially when combined with GH, showed greater cell
proliferation when the difference in growth from 24 to 72 hours was evaluated. GH
appeared to modify the polymer surface, with increased roughness and
microporosity. This feature was more evident in the PLGA + GH combination.
CONCLUSION: The biomaterials tested showed pronounced cell adhesion in all test
groups, and GH appeared to contribute to the increase in cell proliferation,
especially when combined with PLGA as compared with pure PLGA. Further studies
are required to clarify this potential for development of new biomaterials.
PMID- 28494050
TI - Determinants, Associations, Consequences, and Prevention of Readmissions After
Transcatheter Aortic Valve Replacement.
PMID- 28494051
TI - Declining Incidence Rates of Prostate Cancer in the United States: Is This Good
News or Not?
PMID- 28494053
TI - Myeloma Minimal Residual Disease and Surrogacy-Reply.
PMID- 28494054
TI - Conservative Treatment of Isolated Cricoid Cartilage Fractures From Blunt Trauma.
PMID- 28494052
TI - Association of Minimal Residual Disease With Clinical Outcome in Pediatric and
Adult Acute Lymphoblastic Leukemia: A Meta-analysis.
AB - Importance: Minimal residual disease (MRD) refers to the presence of disease in
cases deemed to be in complete remission by conventional pathologic analysis.
Assessing the association of MRD status following induction therapy in patients
with acute lymphoblastic leukemia (ALL) with relapse and mortality may improve
the efficiency of clinical trials and accelerate drug development. Objective: To
quantify the relationships between event-free survival (EFS) and overall survival
(OS) with MRD status in pediatric and adult ALL using publications of clinical
trials and other databases. Data Sources: Clinical studies in ALL identified via
searches of PubMed, MEDLINE, and clinicaltrials.gov. Study Selection: Our search
and study screening process adhered to the PRISMA Guidelines. Studies that
addressed EFS or OS by MRD status in patients with ALL were included; reviews,
abstracts, and studies with fewer than 30 patients or insufficient MRD
description were excluded. Data Extraction and Synthesis: Study sample size,
patient age, follow-up time, timing of MRD assessment (postinduction or
consolidation), MRD detection method, phenotype/genotype (B cell, T cell,
Philadelphia chromosome), and EFS and OS. Searches of PubMed and MEDLINE
identified 566 articles. A parallel search on clinicaltrials.gov found 67 closed
trials and 62 open trials as of 2014. Merging results of 2 independent searches
and applying exclusions gave 39 publications in 3 arms of patient populations
(adult, pediatric, and mixed). We performed separate meta-analyses for each of
these 3 subpopulations. Results: The 39 publications comprised 13 637 patients:
16 adult studies (2076 patients), 20 pediatric (11 249 patients), and 3 mixed
(312 patients). The EFS hazard ratio (HR) for achieving MRD negativity is 0.23
(95% Bayesian credible interval [BCI] 0.18-0.28) for pediatric patients and 0.28
(95% BCI, 0.24-0.33) for adults. The respective HRs in OS are 0.28 (95% BCI, 0.19
0.41) and 0.28 (95% BCI, 0.20-0.39). The effect was similar across all subgroups
and covariates. Conclusions and Relevance: The value of having achieved MRD
negativity is substantial in both pediatric and adult patients with ALL. These
results are consistent across therapies, methods of and times of MRD assessment,
cutoff levels, and disease subtypes. Minimal residual disease status warrants
consideration as an early measure of disease response for evaluating new
therapies, improving the efficiency of clinical trials, accelerating drug
development, and for regulatory approval. A caveat is that an accelerated
approval of a particular new drug using an intermediate end point, such as MRD,
would require confirmation using traditional efficacy end points.
PMID- 28494055
TI - Modern Management of Nasal Hemangiomas.
AB - Importance: Current treatment approaches for infantile hemangiomas of the nose
include observation, pharmacologic agents, surgery, and/or laser therapy. Because
of the known functional, social, and cosmetic effect of nasal deformities,
obtaining the best possible result is critical. Optimal timing, type, duration,
and extent of therapy remain unclear. Observations: Results of a review of 86
patients (64 females and 22 males; mean age, 4.8 months [range, 2 days-23 years])
with infantile hemangiomas of the nose treated from January 1, 1999, to December
31, 2015, and a review of the literature are presented to gain insight into the
preferred approach to the treatment of these lesions. Patients underwent single
modality and multimodality treatment with pulsed-dye laser (n = 73), oral
corticosteroids (n = 11), intralesional corticosteroids (n = 2), propranolol
hydrochloride (n = 30), and surgery (n = 50). The treatment decision algorithms
and outcomes based on tumor phase and infantile hemangioma subtype are reviewed
in detail. Nine articles met the criteria to be included in the literature
review. Literature from the era before the approval of propranolol advocates for
early use of oral or intralesional corticosteroids followed by surgery or pulsed
dye laser in cases of unacceptable outcomes. Literature from the era after the
approval of propranolol supports early initiation of oral beta-blockers until
proliferation ceases or until additional intervention is necessary. Conclusions
and Relevance: Despite a lack of higher levels of evidence, there exists a
general consensus between the literature and clinical experience advocating for
early multimodality treatment to achieve the best result possible by the time the
children reach certain sociodevelopmental milestones.
PMID- 28494057
TI - Biomechanics Education Redux.
PMID- 28494056
TI - Comparison of Automated Posttonsillectomy Bleed Capture With Self-report.
AB - Importance: Tonsillectomy is one of the most common procedures performed by
otolaryngologists and is associated with postoperative bleeding. Bleed rates are
usually monitored by self-report. Objective: To evaluate whether using automated
capture and reporting of pediatric posttonsillectomy bleeding is feasible and
accurate compared with traditional self-reporting by the surgical team. Design,
Setting, and Participants: An automated complication-reporting algorithm was
designed to query the local health information exchange and then tested against
self-reported tonsillectomy complication data collected from January 1, 2014,
through December 31, 2015, at a tertiary pediatric hospital. The algorithm
identified patients undergoing tonsillectomy and searched their postoperative
encounters for a hand-selected set of diagnosis codes from the International
Classification of Diseases, Ninth Revision and International Statistical
Classification of Diseases and Related Health Problems, Tenth Revision and free
text words to identify complication events. Five months of the 2014-2015 data set
were used to help design the algorithm. Data from the remaining 19 months were
compared with self-reported complications. Main Outcomes and Measures: Automated
system findings compared with self-reported bleeding events. Results: During the
19-month period, 1017 tonsillectomies were performed. We compared the algorithm's
effectiveness in finding tonsillectomy and adenotonsillectomy procedures for the
evaluated surgeons with the hand-reviewed master tonsillectomy list. The
algorithm reported 51 false-positive (5.01% missed) and 74 false-negative (7.28%
misidentified) procedures. The algorithm agreed with self-report for 986
tonsillectomies and disagreed on 31 cases (3.05%) (kappa = 0.69; 95% CI, 0.66
0.73). The algorithm was found to be sensitive to correctly identifying 60.53%
(95% CI, 48.63%-71.34%) of tonsillectomies as having bleeding complications, with
a specificity of 98.30% (95% CI, 97.19%-98.99%). Conclusions and Relevance:
Capture of posttonsillectomy bleeding is possible through an automatic search of
the medical record, although the algorithm will require continued refinement.
Leveraging health information exchange data increases the possibilities of
capturing complications at hospitals outside the local health system. Use of
these algorithms will allow repeatable automated feedback to be provided to
surgeons on a cyclical basis.
PMID- 28494058
TI - Management of Chronic Pain in the Aftermath of the Opioid Backlash.
PMID- 28494059
TI - Health Literacy in Patients With Head and Neck Cancer: An Understudied Issue.
PMID- 28494060
TI - beta-Zone Parapapillary Atrophy and Rates of Glaucomatous Visual Field
Progression: African Descent and Glaucoma Evaluation Study.
AB - Importance: beta-zone parapapillary atrophy (betaPPA) has been reported as a risk
factor for glaucoma onset and progression. Previous studies have shown that the
prevalence of betaPPA differs between individuals of African descent (AD) and
European descent (ED). Objective: To test whether the association between the
presence and progression of betaPPA vs visual field progression of glaucoma
differs between these 2 ancestry groups. Design, Setting, and Participants: In a
prospective, multicenter, longitudinal cohort study, 634 individuals (1090 eyes)
enrolled in the African Descent and Evaluation Study (ADAGES) with a diagnosis of
glaucomatous optic neuropathy (GON) or ocular hypertension (OHT) and at least 2
disc stereophotographs were included. Two graders masked to clinical and ancestry
data reviewed and graded the baseline and last disc stereophotographs for the
presence of betaPPA at baseline and betaPPA progression (development or
enlargement). Mixed-effects linear models were tested with visual field mean
deviation as a dependent variable and time (alone and with interaction terms) as
independent variables. ADAGES enrollment began in January 2003 and ended in July
2006; follow-up ended in 2016. Exposures: Disc stereophotographs. Main Outcomes
and Measures: Progression of betaPPA in AD and ED individuals. Results: In 634
patients, a total of 814 eyes of AD (395 eyes) and ED (419) patients with GON and
276 eyes of AD (106) and ED (170) patients with OHT who were enrolled in ADAGES
were analyzed. There were 336 (53.0%) women in the study; mean (SD) age was 61.9
(12.7) years. In the OHT group, the association between betaPPA at baseline and
visual field progression was not significantly different between AD and ED eyes
(beta = 0.071; 95% CI, -0.016 to 0.158; P = .11), nor was the association between
betaPPA progression and visual field progression (beta = 0.020; 95% CI, -0.465 to
0.506; P = .93). In the GON group, ED eyes with baseline betaPPA progressed
faster than did AD eyes with baseline betaPPA (beta = -0.124; 95% CI, -0.241 to
0.007; P = .04), although the association between betaPPA progression and visual
field progression did not differ significantly between race groups (beta =
0.101; 95% CI, -0.323 to 0.119; P = .37). Conclusions and Relevance: Race had a
significant effect on the association between baseline betaPPA and rates of
visual field progression in eyes with GON. Progression of betaPPA was not
associated with faster visual field progression in either racial group.
PMID- 28494062
TI - Conjunctival Lesion in a Patient With Ocular Graft-vs-Host Disease.
PMID- 28494061
TI - Association Between Hospital Volume and 30-Day Readmissions Following
Transcatheter Aortic Valve Replacement.
AB - Importance: With the approval of transcatheter aortic valve replacement (TAVR)
for patients with severe symptomatic aortic stenosis at intermediate surgical
risk, TAVR volume is projected to increase exponentially in the United States.
The 30-day readmission rate for TAVR was recently reported at 17.9%. The
association between institutional TAVR volume and the 30-day readmission metric
has not been examined. Objective: To assess the association between hospital TAVR
volume and 30-day readmission. Design, Setting, and Participants: In this
observational study, we used the 2014 Nationwide Readmissions Database to
identify hospitals with established TAVR programs (performing at least 5 TAVRs in
the first quarter of 2014). Based on annual TAVR volume, hospitals were
classified as low (<50), medium (>=50 to <100), and high (>=100) volume. Rates,
causes, and costs of 30-day readmissions were compared between low-, medium-, and
high-volume hospitals. Data were analyzed from November to December 2016.
Exposure: Transcatheter aortic valve replacement. Main Outcomes and Measures:
Thirty-day readmissions. Results: Of 129 hospitals included in this study, 20
(15.5%) were categorized as low volume, 47 (36.4%) as medium volume, and 62
(48.1%) as high volume. Of 16 252 index TAVR procedures, 663 (4.1%), 3067
(18.9%), and 12 522 (77.0%) were performed at low-, medium-, and high-volume
hospitals, respectively. Thirty-day readmission rates were significantly lower in
high-volume compared with medium-volume (adjusted odds ratio, 0.76; 95% CI, 0.68
0.85; P < .001) and low-volume (adjusted odds ratio, 0.75; 95% CI, 0.60-0.92; P =
.007) hospitals. Noncardiac readmissions were more common in low-volume hospitals
(65.6% vs 60.6% in high-volume hospitals), whereas cardiac readmissions were more
common in high-volume hospitals (39.4% vs 34.4% in low-volume hospitals). There
were no significant differences in length of stay and costs per readmission among
the 3 groups (mean [SD], 5.5 [5.0] days vs 5.9 [7.5] days vs 6.0 [5.8] days; P =
.74, and $13 886 [18 333] vs $14 135 [17 939] vs $13 432 [15 725]; P = .63,
respectively). Conclusions and Relevance: We report for the first time, to our
knowledge, an inverse association between hospital TAVR volume and 30-day
readmissions. Lower readmission at higher-volume hospitals was associated with
significantly lower cost to the health care system.
PMID- 28494064
TI - Myeloma Minimal Residual Disease and Surrogacy.
PMID- 28494065
TI - Alternative Pathways to Board Recertification: To What End?
PMID- 28494063
TI - Efficacy and Adverse Effects of Atropine in Childhood Myopia: A Meta-analysis.
AB - Importance: Some uncertainty about the clinical value and dosing of atropine for
the treatment of myopia in children remains. Objective: To evaluate the efficacy
vs the adverse effects of various doses of atropine in the therapy for myopia in
children. Data Sources: Data were obtained from PubMed, EMBASE, and the Cochrane
Central Register of Controlled Trials, from inception to April 30, 2016. The
reference lists of published reviews and clinicaltrials.gov were searched for
additional relevant studies. Key search terms included myopia, refractive errors,
and atropine. Only studies published in English were included. Study Selection:
Randomized clinical trials and cohort studies that enrolled patients younger than
18 years with myopia who received atropine in at least 1 treatment arm and that
reported the annual rate of myopia progression and/or any adverse effects of
atropine therapy were included in the analysis. Data Extraction and Synthesis:
Two reviewers independently abstracted the data. Heterogeneity was statistically
quantified by Q, H, and I2 statistics, and a meta-analysis was performed using
the random-effects model. The Cochrane Collaboration 6 aspects of bias and the
Newcastle-Ottawa Scale were used to assess the risk for bias. Main Outcomes and
Measures: The primary outcome was a difference in efficacy and the presence of
adverse effects at different doses of atropine vs control conditions. The
secondary outcomes included the differences in adverse effects between Asian and
white patients. Results: Nineteen unique studies involving 3137 unique children
were included in the analysis. The weighted mean differences between the atropine
and control groups in myopia progression were 0.50 diopters (D) per year (95% CI,
0.24-0.76 D per year) for low-dose atropine, 0.57 D per year (95% CI, 0.43-0.71 D
per year) for moderate-dose atropine, and 0.62 D per year (95% CI, 0.45-0.79 D
per year) for high-dose atropine (P < .001), which translated to a high effect
size (Cohen d, 0.97, 1.76, and 1.94, respectively). All doses of atropine,
therefore, were equally beneficial with respect to myopia progression (P = .15).
High-dose atropine were associated with more adverse effects, such as the 43.1%
incidence of photophobia compared with 6.3% for low-dose atropine and 17.8% for
moderate-dose atropine (chi22 = 7.05; P = .03). In addition, differences in the
incidence of adverse effects between Asian and white patients were not identified
(chi21 = 0.81; P = .37 for photophobia). Conclusions and Relevance: This meta
analysis suggests that the efficacy of atropine is dose independent within this
range, whereas the adverse effects are dose dependent.
PMID- 28494066
TI - Association Between Middle Ear Cholesteatoma and Chronic Rhinosinusitis.
AB - Importance: Chronic rhinosinusitis (CRS) can cause an obstruction of the tubal
orifice and thereby compromise ventilation of the middle ear. The resulting
negative pressure in the middle ear may, in turn, lead to the formation of an
eardrum retraction pocket and subsequent acquired cholesteatoma. This study
hypothesizes that CRS may increase the risk of cholesteatoma. Objective: To
evaluate the risk of cholesteatoma in patients with CRS. Design, Setting, and
Participants: This study used a nationwide, population-based claims database to
test the hypothesis that CRS may increase the risk of cholesteatoma. The
Longitudinal Health Insurance Database of Taiwan was used to compile data from
(1) 12 670 patients with newly diagnosed CRS between January 1, 1997, and
December 31, 2002, and (2) a comparison cohort of 63 350 matched individuals
without CRS, resulting in a CRS vs control ratio of 1:5. Data analysis was
performed from June 1 to October 27, 2015. Each patient was followed up for 8
years to identify those in whom cholesteatoma subsequently developed. The Kaplan
Meier method was used to determine the cholesteatoma-free survival rate, and the
log-rank test was used to compare survival curves. Cox proportional hazards
regression models were used to compute the 8-year hazard ratios (HRs). Main
Outcomes and Measures: Diagnosis of cholesteatoma. Results: Among the 76 020
patients enrolled in this study, 35 220 (46.3%) were female; mean (SD) age was
27.57 (22.03) years. A total of 209 patients developed cholesteatoma, 66 (101 084
person-years) individuals from the CRS cohort and 143 (506 540 person-years) from
the comparison cohort were diagnosed with cholesteatoma during the 8-year follow
up period. The incidence of cholesteatoma per 1000 person-years was more than
twice as high among patients with CRS (0.65; 95% CI, 0.50-0.81 person-years) than
among those without CRS (0.28; 95% CI, 0.24-0.33). The absolute difference in the
incidence density between CRS and non-CRS group was 0.37 (95% CI, 0.21-0.53) per
1000 patient-years. After adjusting for potential confounders, patients with CRS
had a 69% increased risk of cholesteatoma within 8 years, compared with those
without CRS (HR, 1.69; 95% CI, 1.23-2.32). Patients with CRS presented a
significantly lower 8-year cholesteatoma-free survival rate than did those in the
comparison group. The absolute difference in the 8-year cholesteatoma-free
survival rate between the CRS and non-CRS groups was 0.0029 (95% CI, 0.0016
0.0043). Conclusions and Relevance: This is the first large-scale study, to date,
to demonstrate a prospective link between CRS and the subsequent development of
cholesteatoma within a follow-up period of 8 years. The purpose of the study was
to draw attention to the possibility of development of cholesteatoma among
patients with CRS. Because that possibility exists, clinicians should keep this
association in mind as well as the importance of a thorough head and neck
examination.
PMID- 28494067
TI - Association of Dietary Vitamin K1 Intake With the Incidence of Cataract Surgery
in an Adult Mediterranean Population: A Secondary Analysis of a Randomized
Clinical Trial.
AB - Importance: Cataract, one of the most frequent causes of blindness in developed
countries, is strongly associated with aging. The exact mechanisms underlying
cataract formation are still unclear, but growing evidence suggests a potential
role of inflammatory and oxidative processes. Therefore, antioxidant and anti
inflammatory factors of the diet, such as vitamin K1, could play a protective
role. Objective: To examine the association between dietary vitamin K1 intake and
the risk of incident cataracts in an elderly Mediterranean population. Design,
Setting, and Participants: A prospective analysis was conducted in 5860
participants from the Prevencion con Dieta Mediterranea Study, a randomized
clinical trial executed between 2003 and 2011. Participants were community
dwelling men (44.2%) and women (55.8%), and the mean (SD) age was 66.3 (6.1)
years. Main Outcomes and Measures: Dietary vitamin K1 intake was evaluated using
a validated food frequency questionnaire. The time to the cataract event was
calculated as the time between recruitment and the date of the occurrence to
cataract surgery, the time to the last visit of the follow-up, date of death, or
the end of the study. Hazard ratios and 95% CIs for cataract incidence were
estimated with a multivariable Cox proportional hazards model. Results:
Participants were community-dwelling men (44.2%; n = 868) and women (55.8%; n =
1086), and the mean (SD) age was 66.3 (6.1) years. After a median of 5.6 years
follow-up, we documented a total of 768 new cataracts. Participants in the
highest tertile of dietary vitamin K1 intake had a lower risk of cataracts than
those in the lowest tertile (hazard ratio, 0.71; 95% CI, 0.58-0.88; P = .002),
after adjusting for potential confounders. Conclusions and Relevance: High intake
of dietary vitamin K1 was associated with a reduced risk of cataracts in an
elderly Mediterranean population even after adjusting by other potential
confounders. Trial Registration: isrctn.org: ISRCTN35739639.
PMID- 28494068
TI - A Comparison of Costal Cartilage Warping Using Oblique Split vs Concentric
Carving Methods.
AB - Importance: Warping of costal cartilage is well described; however, its strength
and abundance still make it a desirable graft material, especially in complex
reconstructive rhinoplasty. Despite multiple methods of cartilage harvest,
carving, and preimplantation treatment being developed over the years, warp
remains a challenging clinical problem. Objective: To assess whether the 30
degrees oblique split method of preparing costal cartilage grafts produces less
warping of the graft than the current standard of harvesting the central segment
of a rib using the concentric carving method. Design, Setting, and Participants:
This in vitro cadaveric study evaluated the warping of costal cartilage grafts
using the oblique split method with an angle of 30 degrees or the concentric
carving method during a 3-month period beginning in December 2014. Main Outcomes
and Measures: Millimeters of warp from baseline (at 1 hour) and at 1, 2, and 3
months, measured in the frontal and lateral planes. Results: Among 74 costal
cartilage grafts (using the oblique split method with an angle of 30 degrees in
41 and the concentric carving method in 33), the mean amount of warp in the
frontal plane was between 1.12 mm (95% CI, 0.96-1.28 mm) and 1.57 mm (95% CI,
0.94-2.20 mm) for the oblique group and between 1.18 mm (95% CI, 0.98-1.38 mm)
and 1.29 mm (95% CI, 0.86-1.72 mm) for the concentric group during the 3-month
period. There was no statistically significant difference in the frontal plane
between the 2 methods at 1 hour (P = .45; 0.10 mm, 95% CI, -0.38 to 0.17 mm), 1
month (P = .32; 0.13 mm, 95% CI, -0.13 to 0.40 mm), 2 months (P = .50; 0.28 mm,
95% CI, -0.55 to 1.11 mm), or 3 months (P = .15; 0.22 mm, 95% CI, -0.08 to 0.52
mm) using the t test, regression analysis, or panel data analysis. Similarly, no
significant difference was found in the lateral plane at 1 hour (P = .89; 0.04
mm, 95% CI, -0.49 to 0.56 mm), 1 month (P = .82; 0.07 mm, 95% CI, -0.56 to 0.70
mm), 2 months (P = .29; 0.40 mm, 95% CI, -0.36 to 1.17 mm), or 3 months (P = .63;
0.22 mm, 95% CI, -0.70 to 1.13 mm) using the t test. Two grafts were excluded due
to desiccation. Conclusions and Relevance: The 30 degrees oblique split and
concentric carving methods of costal cartilage graft carving are equivalent in
terms of the amount of warp. The oblique split method may be superior because of
easier carving and the increased volume of material. Level of Evidence: NA.
PMID- 28494072
TI - Prognostic and Predictive Value of a Breast Cancer Expression Signature in
Localized Prostate Cancer.
PMID- 28494071
TI - Correlation Between Dynamic Contour Tonometry, Uncorrected and Corrected Goldmann
Applanation Tonometry, and Stage of Glaucoma.
AB - Importance: Accurate determination of intraocular pressure (IOP) is crucial for
the diagnosis and management of glaucoma. Objective clinical evaluation of the
correction equations for Goldmann applanation tonometry (GAT) is lacking.
Objectives: To investigate the difference between corrected and conventional GAT
and Pascal dynamic contour tonometry (DCT) measurements, as well as the
correlation between discordant IOP values and stage of glaucoma. Design, Setting,
and Participants: This prospective cross-sectional case series was conducted at
the Department of Ophthalmology, University Hospital Zurich, and Talacker Eye
Center between July 1, 2011, and May 31, 2016, among 112 white patients with
glaucoma. Interventions: Intraocular pressure measurements were performed with
GAT and DCT in a randomized order. Goldmann applanation tonometry measurements
were modified with 5 correction equations. Main Outcomes and Measures: The
primary end point was degree of concordance between corrected or uncorrected GAT
and DCT measurements. The secondary end point was association between discordant
IOP measurements and the stage of glaucoma, as assessed by the Glaucoma Severity
Score. Results: Among the 112 patients (67 women and 45 men; mean [SD] age, 66.3
[13.1] years), 63 of the eyes in the study (56.3%) were left eyes and 85 patients
(75.9%) were taking ocular antihypertensive medications. Mean (SD) IOP was 20.3
(4.5) mm Hg (95% CI, 19.4-21.1) as measured by DCT and 17.0 [4.1] mm Hg (95% CI,
16.3-17.8) as measured by GAT. The mean (SD) discordance between DCT and GAT
measurements was -3.3 (2.0) mm Hg (95% CI, 2.9-3.6). The 5 corrected GAT values
ranged from -2.7 to -5.4 mm Hg compared with DCT. The mean (SD) result of the
Dresdner correction formula (17.6 [4.1] mm Hg) was closer to the DCT measurement
than the original GAT measurement. The mean (SD) Glaucoma Severity Score was 4.7
(3.4) (95% CI, 4.1-5.4). The uncorrected discordance IOPDCT - IOPGAT showed a
positive correlation with the Glaucoma Severity Score (rs = 0.33; P < .001) and a
negative correlation with central corneal thickness (rs = -0.22; P = .02).
Conclusions and Relevance: In comparison with DCT measurements, these data
suggest that GAT values are significantly discordant in eyes with thin corneas
and advanced glaucoma. Application of GAT-based correction formulas involves a
possible risk of creating an even greater number of unpredictable measurement
errors. Hence, we advise with caution, especially pertaining to eyes with thin
corneas, to not place reliance on GAT readings, and abandon any correction
formula. Trial Registration: clinicaltrials.gov Identifier: NCT01474070.
PMID- 28494074
TI - Stop "Adjusting" Intraocular Pressure Measurements.
PMID- 28494073
TI - Associations of Luminal and Basal Subtyping of Prostate Cancer With Prognosis and
Response to Androgen Deprivation Therapy.
AB - Importance: There is a clear need for a molecular subtyping approach in prostate
cancer to identify clinically distinct subgroups that benefit from specific
therapies. Objectives: To identify prostate cancer subtypes based on luminal and
basal lineage and to determine associations with clinical outcomes and response
to treatment. Design, Setting, and Participants: The PAM50 classifier was used to
subtype 1567 retrospectively collected (median follow-up, 10 years) and 2215
prospectively collected prostate cancer samples into luminal- and basal-like
subtypes. Main Outcomes and Measures: Metastasis, biochemical recurrence, overall
survival, prostate cancer-specific survival, associations with biological
pathways, and clinicopathologic variables were the main outcomes. Results: Among
the 3782 samples, the PAM50 classifier consistently segregated prostate cancer
into 3 subtypes in both the retrospective and prospective cohorts: luminal A
(retrospective, 538 [34.3%]; prospective, 737 [33.3%]), luminal B (retrospective,
447 [28.5%]; prospective, 723 [32.6%]), and basal (retrospective, 582 [37.1%];
prospective, 755 [34.1%]). Known luminal lineage markers, such as NKX3.1 and
KRT18, were enriched in luminal-like cancers, and the basal lineage CD49f
signature was enriched in basal-like cancers, demonstrating the connection
between these subtypes and established prostate cancer biology. In the
retrospective cohort, luminal B prostate cancers exhibited the poorest clinical
prognoses on both univariable and multivariable analyses accounting for standard
clinicopathologic prognostic factors (10-year biochemical recurrence-free
survival [bRFS], 29%; distant metastasis-free survival [DMFS], 53%; prostate
cancer-specific survival [PCSS], 78%; overall survival [OS], 69%), followed by
basal prostate cancers (10-year bRFS, 39%; DMFS, 73%; PCSS, 86%; OS, 80%) and
luminal A prostate cancers (10-year bRFS, 41%; DMFS, 73%; PCSS, 89%; OS, 82%).
Although both luminal-like subtypes were associated with increased androgen
receptor expression and signaling, only luminal B prostate cancers were
significantly associated with postoperative response to androgen deprivation
therapy (ADT) in a subset analysis in our retrospective cohorts (n = 315)
matching patients based on clinicopathologic variables (luminal B 10-year
metastasis: treated, 33% vs untreated, 55%; nonluminal B 10-year metastasis:
treated, 37% vs untreated, 21%; P = .006 for interaction). Conclusions and
Relevance: Luminal- and basal-like prostate cancers demonstrate divergent
clinical behavior, and patients with luminal B tumors respond better to
postoperative ADT than do patients with non-luminal B tumors. These findings
contribute novel insight into prostate cancer biology, providing a potential
clinical tool to personalize ADT treatment for prostate cancer by predicting
which men may benefit from ADT after surgery.
PMID- 28494076
TI - The Balance Between Access and Quality in Transcatheter Valve Therapies.
PMID- 28494077
TI - Inadvertent Subconjunctival Injection of a Dexamethasone Implant.
PMID- 28494078
TI - Exclusion of Traumatic Anterior Capsule Laceration Using Anterior Segment Optical
Coherence Tomography.
PMID- 28494075
TI - Six-Year Incidence and Progression of Age-Related Macular Degeneration in Kenya:
Nakuru Eye Disease Cohort Study.
AB - Importance: The incidence of age-related macular degeneration (AMD) is unknown in
Africa. Objective: To estimate the 6-year cumulative incidence and progression of
AMD in older adults (>=50 years old) in Nakuru, Kenya. Design, Setting, and
Participants: This study assessed a population-based cohort with 6-year follow-up
of 4414 participants who had a complete assessment. Random cluster sampling with
probability proportionate to size procedures was used to select a representative,
cross-sectional sample of adults 50 years and older from January 26, 2007,
through November 11, 2008. A 6-year follow-up was undertaken from January 7,
2013, through March 12, 2014. On both occasions, a comprehensive ophthalmic
examination was performed that included logMAR visual acuity, digital retinal
photography, and grading of images at Moorfields Eye Hospital Reading Centre.
Data were collected on general health and risk factors. Main Outcomes and
Measures: Incident AMD in participants with no AMD at baseline and progression
from early to late AMD. Results: A total of 1453 of the 2900 individuals (50.1%)
at risk for AMD were followed up after 6 years (mean [SD] age, 60.7 [8.2] years;
635 female [49.5%]; 799 Kikuyu [62.3%], 324 Kalenjin [25.3%], and 159 other
[12.4%]); 1282 had data on AMD status at follow-up. Of these, 202 developed early
AMD, and no participants developed late AMD. The 6-year weighted (for loss to
follow-up) cumulative incidence of early AMD was 164.2 per 1000 persons (95% CI,
136.7-195.9 per 1000 persons). Two individuals with baseline early AMD from the
142 at risk had developed late AMD at follow-up, with a 6-year cumulative
incidence of progression from early to late AMD of 24.5 per 1000 persons (95% CI,
5.0-111.7 per 1000 persons). Cumulative incidence of AMD increased with age (>=80
years old vs 50-59 years old: 1.8; 95% CI, 0.9-3.5) and was higher in women
(female vs male: 1.6; 95% CI, 1.2-2.1) and persons with diabetes (diabetes vs no
diabetes: 1.7; 95% CI, 1.0-2.8). Conclusions and Relevance: In Kenya, more than
100 000 estimated new cases of AMD, mainly early AMD, will develop every year in
individuals 50 years or older, although a 50% loss to follow-up and wide CIs for
progression to late AMD limit definitive conclusions from these findings.
PMID- 28494079
TI - Numerous Smokestack and Inkblot Pattern Leaks in Central Serous
Chorioretinopathy.
PMID- 28494080
TI - Maxillary Sinus Wall Thickening in Silent Sinus Syndrome.
PMID- 28494084
TI - The use of high throughput DNA sequence analysis to assess the endophytic
microbiome of date palm roots grown under different levels of salt stress.
AB - Date palms are able to grow under diverse abiotic stress conditions including in
saline soils, where microbial communities may be help in the plant's salinity
tolerance. These communities able to produce specific growth promoting substances
can enhance date palm growth in a saline environment. However, these communities
are poorly defined. In the work reported here, the date palm endophytic bacterial
and fungal communities were identified using the pyrosequencing method, and the
microbial differential abundance in the root upon exposure to salinity stress was
estimated. Approximately 150,061 reads were produced from the analysis of six
ribosomal DNA libraries, which were prepared from endophytic microorganisms
colonizing date palm root tissues. DNA sequence analysis of these libraries
predicted the presence of a variety of bacterial and fungal endophytic species,
some known and others unknown. The microbial community compositions of 30% and 8%
of the bacterial and fungal species, respectively, were significantly (p <= 0.05)
altered in response to salinity stress. Differential enrichment analysis showed
that microbe diversity indicated by the Chao, Shannon and Simpson indices were
slightly reduced, however, the overall microbial community structures were not
significantly affected as a consequence of salinity. This may reflect a buffering
effect by the host plant on the internal environments that these communities are
colonizing. Some of the endophytes identified in this study were strains that
were previously isolated from saline and marine environments. This suggests
possible interactions with the plant that are favorable to salinity tolerance in
date palm. [Int Microbiol 19(3):143-155 (2016)].
PMID- 28494083
TI - Phosphate: from stardust to eukaryotic cell cycle control.
AB - Phosphorus is a pivotal element in all biochemical systems: it serves to store
metabolic energy as ATP, it forms the backbone of genetic material such as RNA
and DNA, and it separates cells from the environment as phospholipids. In
addition to this "big hits", phosphorus has recently been shown to play an
important role in other important processes such as cell cycle regulation. In the
present review, we briefly summarize the biological processes in which phosphorus
is involved in the yeast Saccharomyces cerevisiae before discussing our latest
findings on the role of this element in the regulation of DNA replication in this
eukaryotic model organism. We describe both the role of phosphorus in the
regulation of G1 progression by means of the Cyclin Dependent Kinase (CDK) Pho85
and the stabilization of the cyclin Cln3, as well as the role of other molecule
composed of phosphorus-the polyphosphate-in cell cycle progression, dNTP
synthesis, and genome stability. Given the eminent role played by phosphorus in
life, we outline the future of phosphorus in the context of one of the main
challenges in human health: cancer treatment. [Int Microbiol 19(3):133-141
(2016)].
PMID- 28494085
TI - Atypical enteropathogenic Escherichia coli (aEPEC) in children under five years
old with diarrhea in Quito (Ecuador).
AB - Enteropathogenic Escherichia coli (EPEC) remain one the most important pathogens
infecting children and they are one of the main causes of persistent diarrhea
worldwide. In this study, we have isolated EPEC from 94 stool samples of children
under five years old with diarrheal illness in the area of Quito (Ecuador), and
we have determined the occurrence of the two subtypes of EPEC, typical EPEC
(tEPEC) and atypical (aEPEC), by PCR amplification of the genes eae (attaching
and effacing) and bfp (bundle- forming pilus). Typical EPEC is positive for eae
and bfp genes while aEPEC is positive only for eae. Our results suggest that
aEPEC is the most prevalent subtype in Quito (89.36 %), while subtype tEPEC is
less prevalent (10.64 %). [Int Microbiol 19(3):157-160 (2016)].
PMID- 28494086
TI - Functional ecology of soil microbial communities along a glacier forefield in
Tierra del Fuego (Chile).
AB - A previously established chronosequence from Pia Glacier forefield in Tierra del
Fuego (Chile) containing soils of different ages (from bare soils to forest ones)
is analyzed. We used this chronosequence as framework to postulate that microbial
successional development would be accompanied by changes in functionality. To
test this, the GeoChip functional microarray was used to identify diversity of
genes involved in microbial carbon and nitrogen metabolism, as well as other
genes related to microbial stress response and biotic interactions. Changes in
putative functionality generally reflected succession-related taxonomic
composition of soil microbiota. Major shifts in carbon fixation and catabolism
were observed, as well as major changes in nitrogen metabolism. At initial
microbial dominated succession stages, microorganisms could be mainly involved in
pathways that help to increase nutrient availability, while more complex
microbial transformations such as denitrification and methanogenesis, and later
degradation of complex organic substrates, could be more prevalent at vegetated
successional states. Shifts in virus populations broadly reflected changes in
microbial diversity. Conversely, stress response pathways appeared relatively
well conserved for communities along the entire chronosequence. We conclude that
nutrient utilization is likely the major driver of microbial succession in these
soils. [Int Microbiol 19(3):161-173 (2016)].
PMID- 28494087
TI - Investigation of twenty selected medicinal plants from Malaysia for anti
Chikungunya virus activity.
AB - Chikungunya virus is a reemerging arbovirus transmitted mainly by Aedes
mosquitoes. As there are no specific treatments available, Chikungunya virus
infection is a significant public health problem. This study investigated 120
extracts from selected medicinal plants for anti-Chikungunya virus activity. The
plant materials were subjected to sequential solvent extraction to obtain six
different extracts for each plant. The cytotoxicity and antiviral activity of
each extract were examined using African monkey kidney epithelial (Vero) cells.
The ethanol, methanol and chloroform extracts of Tradescantia spathacea
(Commelinaceae) leaves showed the strongest cytopathic effect inhibition on Vero
cells, resulting in cell viabilities of 92.6% +/- 1.0% (512 MUg/ml), 91.5% +/-
1.7% (512 MUg/ml) and 88.8% +/- 2.4% (80 MUg/ml) respectively. However,
quantitative RT-PCR analysis revealed that the chloroform extract of Rhapis
excelsa (Arecaceae) leaves resulted in the highest percentage of reduction of
viral load (98.1%), followed by the ethyl acetate extract of Vernonia amygdalina
(Compositae) leaves (95.5%). The corresponding 50% effective concentrations
(EC50) and selectivity indices for these two extracts were 29.9 +/- 0.9 and 32.4
+/- 1.3 MUg/ml, and 5.4 and 5.1 respectively. Rhapis excelsa and Vernonia
amygdalina could be sources of anti-Chikungunya virus agents. [Int Microbiol
19(3):175-182 (2016)].
PMID- 28494088
TI - Peripheral nerve blocks for hip fractures.
AB - BACKGROUND: Various nerve blocks with local anaesthetic agents have been used to
reduce pain after hip fracture and subsequent surgery. This review was published
originally in 1999 and was updated in 2001, 2002, 2009 and 2017. OBJECTIVES: This
review focuses on the use of peripheral nerves blocks as preoperative analgesia,
as postoperative analgesia or as a supplement to general anaesthesia for hip
fracture surgery. We undertook the update to look for new studies and to update
the methods to reflect Cochrane standards. SEARCH METHODS: For the updated
review, we searched the following databases: the Cochrane Central Register of
Controlled Trials (CENTRAL; 2016, Issue 8), MEDLINE (Ovid SP, 1966 to August week
1 2016), Embase (Ovid SP, 1988 to 2016 August week 1) and the Cumulative Index to
Nursing and Allied Health Literature (CINAHL) (EBSCO, 1982 to August week 1
2016), as well as trial registers and reference lists of relevant articles.
SELECTION CRITERIA: We included randomized controlled trials (RCTs) involving use
of nerve blocks as part of the care provided for adults aged 16 years and older
with hip fracture. DATA COLLECTION AND ANALYSIS: Two review authors independently
assessed new trials for inclusion, determined trial quality using the Cochrane
tool and extracted data. When appropriate, we pooled results of outcome measures.
We rated the quality of evidence according to the GRADE Working Group approach.
MAIN RESULTS: We included 31 trials (1760 participants; 897 randomized to
peripheral nerve blocks and 863 to no regional blockade). Results of eight trials
with 373 participants show that peripheral nerve blocks reduced pain on movement
within 30 minutes of block placement (standardized mean difference (SMD) -1.41,
95% confidence interval (CI) -2.14 to -0.67; equivalent to -3.4 on a scale from 0
to 10; I2 = 90%; high quality of evidence). Effect size was proportionate to the
concentration of local anaesthetic used (P < 0.00001). Based on seven trials with
676 participants, we did not find a difference in the risk of acute confusional
state (risk ratio (RR) 0.69, 95% CI 0.38 to 1.27; I2 = 48%; very low quality of
evidence). Three trials with 131 participants reported decreased risk for
pneumonia (RR 0.41, 95% CI 0.19 to 0.89; I2 = 3%; number needed to treat for an
additional beneficial outcome (NNTB) 7, 95% CI 5 to 72; moderate quality of
evidence). We did not find a difference in risk of myocardial ischaemia or death
within six months, but the number of participants included was well below the
optimal information size for these two outcomes. Two trials with 155 participants
reported that peripheral nerve blocks also reduced time to first mobilization
after surgery (mean difference -11.25 hours, 95% CI -14.34 to -8.15 hours; I2 =
52%; moderate quality of evidence). One trial with 75 participants indicated that
the cost of analgesic drugs was lower when they were given as a single shot block
(SMD -3.48, 95% CI -4.23 to -2.74; moderate quality of evidence). AUTHORS'
CONCLUSIONS: High-quality evidence shows that regional blockade reduces pain on
movement within 30 minutes after block placement. Moderate-quality evidence shows
reduced risk for pneumonia, decreased time to first mobilization and cost
reduction of the analgesic regimen (single shot blocks).
PMID- 28494089
TI - Evaluation of the tumor registration error in biopsy procedures performed under
real-time PET/CT guidance.
AB - PURPOSE: The purpose of this study is to quantify tumor displacement during real
time PET/CT guided biopsy and to investigate correlations between tumor
displacement and false-negative results. METHODS: 19 patients who underwent real
time 18 F-FDG PET-guided biopsy and were found positive for malignancy were
included in this study under IRB approval. PET/CT images were acquired for all
patients within minutes prior to biopsy to visualize the FDG-avid region and plan
the needle insertion. The biopsy needle was inserted and a post-insertion CT scan
was acquired. The two CT scans acquired before and after needle insertion were
registered using a deformable image registration (DIR) algorithm. The DIR
deformation vector field (DVF) was used to calculate the mean displacement
between the pre-insertion and post-insertion CT scans for a region around the tip
of the biopsy needle. For 12 patients one biopsy core from each was tracked
during histopathological testing to investigate correlations of the mean
displacement between the two CT scans and false-negative or true-positive biopsy
results. For 11 patients, two PET scans were acquired; one at the beginning of
the procedure, pre-needle insertion, and an additional one with the needle in
place. The pre-insertion PET scan was corrected for intraprocedural motion by
applying the DVF. The corrected PET was compared with the post-needle insertion
PET to validate the correction method. RESULTS: The mean displacement of tissue
around the needle between the pre-biopsy CT and the postneedle insertion CT was
5.1 mm (min = 1.1 mm, max = 10.9 mm and SD = 3.0 mm). For mean displacements
larger than 7.2 mm, the biopsy cores gave false-negative results. Correcting pre
biopsy PET using the DVF improved the PET/CT registration in 8 of 11 cases.
CONCLUSIONS: The DVF obtained from DIR of the CT scans can be used for evaluation
and correction of the error in needle placement with respect to the FDG-avid
area. Misregistration between the pre-biopsy PET and the CT acquired with the
needle in place was shown to correlate with false negative biopsy results.
PMID- 28494090
TI - Technical Note: Transconvolution based equalization of positron energy effects
for the use of 68 Ge/68 Ga phantoms in determining 18 F PET recovery.
AB - PURPOSE: Avoiding measurement variability from 18 F phantom preparation by using
68 Ge/68 Ga phantoms for the determination of 18 F recovery curves (RC) in
clinical quality assurance measurements and for PET/CT site qualification in
multicentre clinical trials. METHODS: RCs were obtained from PET/CT measurements
of seven differently sized phantom spheres filled either with 18 F or with 68 Ga.
RCs for the respective other isotope were then determined by two different
methods: In the first method, images were convolved with positron range
transconvolution functions derived from positron annihilation distributions found
in literature. This method generated recasted images matching images using the
respective other isotope. In the second method, the PET/CT system's isotope
independent (intrinsic) point spread function was determined from said phantom
measurements and convolved with numerical representations simulating hot spheres
filled with the respective other isotope. These simulations included the isotope
specific positron annihilation distributions. Recovered activity concentrations
were compared between recasted images, simulated images, and the originally
acquired images. RESULTS: 18 F and 68 Ga recovery was successfully determined
from image acquisitions of the respective opposite isotope as well as from the
simulations. 68 Ga RCs derived from 18 F data had a normalized root-mean-square
deviation (NRMSD) from real 68 Ga measurements of 0.019% when using the first
method and of 0.008% when using the second method. 18 F RCs derived from 68 Ga
data had a NRMSD from real 18 F measurements of 0.036% when using the first
method and of 0.038% when using the second method. CONCLUSIONS: Applying the
principles of transconvolution, 18 F RCs can be recalculated from 68 Ga phantom
measurements with excellent accuracy. The maximal additionally introduced error
was below 0.4% of the error currently accepted for RCs in the site qualification
of multicentre clinical trials by the EARL program of the European Association of
Nuclear Medicine (EANM). Therefore, our methods legitimately allow for the use of
long-lived solid state 68 Ge/68 Ga phantoms instead of manually prepared 18 F
phantoms to characterize comparability of 18 F measurements across different
imaging sites or of longitudinal 18 F measurements at a single PET/CT system.
PMID- 28494092
TI - Incidence of human cytomegalovirus infection and T-cell response in patients with
psoriasis before and during antitumour necrosis factor-alpha therapy.
PMID- 28494091
TI - Fermentation Characteristics and Aromatic Profile of Plum Wines Produced with
Indigenous Microbiota and Pure Cultures of Selected Yeast.
AB - The aim of this study was to assess and compare fermentation characteristics and
aromatic profile of plum wines produced with indigenous microbiota and pure
cultures of different selected yeast. Experiments were carried out with plum
(Prunus domestica L.) varieties of different fruit ripening times (Cacanska rana,
Cacanska lepotica, and Pozegaca). Wine fermentations were conducted by the
activity of indigenous microbiota, commercially available Saccharomyces
cerevisiae and Saccharomyces bayanus yeast strains and joint activity of
Schizosaccharomyces pombe and S. cerevisiae (sequential inoculation).
Statistically significant differences in fermentative characteristics and the
content of certain volatile compounds were observed as a result of metabolic
activity of various indigenous and/or selected yeasts during fermentation of plum
pomace. Minimal duration of fermentation (4 to 5 d) and fastest ethanol
production rate (from 12.3 to 15.5 g/L/d) were the characteristics of the studied
S. cerevisiae strains. Isobutanol, 3-methyl-1-butanol, 1-heptanol, and 1-octanol
were the most prevalent higher alcohols in the tested plum wine samples. The
predominant ester in plum wines was ethyl acetate, ethyl lactate, amyl acetate,
isoamyl acetate, and ethyl palmitate, esters responsible for the floral and
fruity olfactory tones, were also present in large amounts. Also, the use of S.
cerevisiae strains resulted in the production of plum wines with better sensory
characteristics than ones produced with other investigated yeasts. Obtained
results are significant since there is limited data on the compounds responsible
for the unique flavor of plum wine, as well as on the impact of different yeast
starter cultures application on the overall quality of fruit wines.
PMID- 28494093
TI - Study on the Removal of Cadmium in Rice Using Microbial Fermentation Method.
AB - This work mainly examined how to remove cadmium in rice by fermentation, the
removal mechanisms, and the quality of fermented rice in order to utilize cadmium
contaminated rice. The fermentation time, temperature, liquid ratio, inoculant
levels, and number of washes were varied to optimize the efficiency of cadmium
removal. The optimum fermentation process, in which the rate of cadmium removal
from the rice is 80.84%, required an inoculant amount of 0.1%, a liquid ratio of
1:1, a period of 60 h at 37 degrees C, and subsequently washed with water 4
times. The physicochemical properties of raw cadmium-contaminated rice and
fermented rice were studied. Results showed that the pasting temperature of the
fermented rice became lower, and temperature at which pasting starts dropped but
the endothermic enthalpy increased, implying that the protein content in the rice
decreased during the fermentation. It suggested that the crystal structure of
rice starch changed and fermentation did not result in the formation of new
chemical bonds or functional groups in the rice. Microbial fermentation method
can therefore effectively reduce cadmium level in contaminated rice.
PMID- 28494094
TI - Effect of Different Extrusion Parameters on Dietary Fiber in Wheat Bran and Rye
Bran.
AB - Wheat bran and rye bran are mostly used as animal feed today, but their high
content of dietary fiber and bioactive components are beneficial to human health.
Increased use of bran as food raw material could therefore be desirable. However,
bran mainly contains unextractable dietary fiber and deteriorates the sensory
properties of products. Processing by extrusion could increase the extractability
of dietary fiber and increase the sensory qualities of bran products. Wheat bran
and rye bran were therefore extruded at different levels of moisture content,
screw speed and temperature, in order to find the optimal setting for increased
extractability of dietary fiber and positive sensory properties. A water content
of 24% for wheat bran and 30% for rye bran, a screw speed of 400 rpm, and a
temperature of 130 degrees C resulted in the highest extractability of total
dietary fiber and arabinoxylan. Arabinoxylan extractability increased from 5.8%
in wheat bran to 9.0% in extruded wheat bran at those settings, and from 14.6% to
19.2% for rye bran. Total contents of dietary fiber and arabinoxylan were not
affected by extrusion. Content of beta-glucan was also maintained during
extrusion, while its molecular weight decreased slightly and extractability
increased slightly. Extrusion at these settings is therefore a suitable process
for increasing the use of wheat bran and rye bran as a food raw material.
PMID- 28494095
TI - Comparison of 192 Ir, 169 Yb, and 60 Co high-dose rate brachytherapy sources for
skin cancer treatment.
AB - PURPOSE: To evaluate the possibility of utilizing the high-dose rate (HDR) 169 Yb
and 60 Co sources, in addition to 192 Ir, for the treatment of skin malignancies
with conical applicators. METHODS: Monte Carlo (MC) simulations were used to
benchmark the dosimetric parameters of single 169 Yb (4140), 60 Co (Co0.A86), and
192 Ir (mHDR-V2) brachytherapy sources in a water phantom and compared their
results against published data. A standard conical tungsten alloy Leipzig-style
applicator (Stand.Appl) was used for determination of the dose distributions at
various depths with a single dwell position of the HDR sources. The HDR sources
were modeled with its long axis parallel to the treatment plane within the
opening section of the applicator. The source-to-surface distance (SSD) was 1.6
cm, which included a 0.1 cm thick removable plastic end-cap used for clinical
applications. The prescription depth was considered to be 0.3 cm in a water
phantom following the definitions in the literature for this treatment technique.
Dose distributions generated with the Stand.Appl and the 169 Yb and 60 Co sources
have been compared with those of the 192 Ir source, for the same geometry. Then,
applicator wall thickness for the 60 Co source was increased (doubled) in MC
simulations in order to minimize the leakage dose and penumbra to levels that
were comparable to that from the 192 Ir source. For each source-applicator
combination, the optimized plastic end-cap dimensions were determined in order to
avoid over-dosage to the skin surface. RESULTS: The normalized dose profiles at
the prescription depth for the 169 Yb-Stand.Appl and the 60 Co-double-wall
applicator were found to be similar to that of the 192 Ir-Stand.Appl, with
differences < 2.5%. The percentage depth doses (PDD) for the 192 Ir-, 169 Yb- and
60 Co-Stand.Appl were found to be comparable to the values with the 60 Co-double
walled applicator, with differences < 1.7%. The applicator output-factors at the
prescription depth were also comparable at 0.309, 0.316, and 0.298 (cGy/hU) for
the 192 Ir-, 169 Yb-Stand.Appl, and 60 Co-double-wall applicators respectively.
The leakage dose around the Stand.Appl for distance > 2 cm from the applicator
surface was < 5% for 192 Ir, < 1% for 169 Yb, and < 18% for 60 Co relative to the
prescription dose. However, using the double-walled applicator for the 60 Co
source reduced the leakage dose to around 5% of the prescription dose, which is
comparable with that of the 192 Ir source. The optimized end-cap thicknesses for
the 192 Ir-, 169 Yb-Stand.Appl, and the 60 Co-double-wall applicator were found
to be 1.1, 0.6, and 3.7 mm respectively. CONCLUSIONS: Application of the 169 Yb
(with Stand.Appl) or the 60 Co source (with double-wall applicator) has been
evaluated as alternatives to the existing 192 Ir source (with Stand.Appl) for the
HDR brachytherapy of skin cancer patients. These alternatives enable the clinics
that may have 169 Yb or 60 Co sources instead of the 192 Ir source to perform the
skin brachytherapy and achieve comparable results. The conical surface
applicators must be used with a protective plastic end-cap to eliminate the
excess electrons that are created in the source and applicator, in order to avoid
skin surface over-dosage. The treatment times for the 60 Co source remain to be
determined. Additionally, for 169 Yb, the source needs to be changed on monthly
basis due to its limited half-life.
PMID- 28494096
TI - Physicochemical Properties and Antioxidant Capacity of Chinese Olive (Canarium
album L.) Cultivars.
AB - In this study, the physicochemical characteristics and antioxidant potentials of
10 Chinese olive cultivars were investigated. Considerable differences were found
between cultivars in weight, edible yield, water content, size, shape, total
soluble solids, and total titratable acidity. The major sugars and organic acids
in all the cultivars were glucose, fructose, and malic acid. Phenolics were the
most abundant antioxidants (1174.0 to 1799.6 mg gallic acid equivalents/100 g
fresh weight). Twelve phenolic compounds were identified and quantified by UPLC
MS/MS. Six compounds were identified first in the Chinese olive, with 3-O
galloylquinic acid and geraniin isomers as the most abundant compounds. The
results also indicated that the phenolic content (TPC) correlated with the
antioxidant properties of Chinese olive fruit extracts. A principal component
analysis indicated that the Tantou and Tanxiang cultivars were a valuable source,
with high TPC and antioxidant activity, whereas Maken22, Changying, and Green
changying cultivars may be eaten fresh and had high sugar and low phenolic
contents. This information will be useful for selecting suitable cultivars for
industry and the market.
PMID- 28494097
TI - An open, multicentre, randomized clinical study in patients with bullous
pemphigoid comparing methylprednisolone and azathioprine with methylprednisolone
and dapsone.
AB - BACKGROUND: Current treatment of bullous pemphigoid (BP) is based on the long
term use of topical and/or systemic corticosteroids, which are associated with a
high rate of adverse events and increased mortality. OBJECTIVES: To study the
corticosteroid-sparing potential of azathioprine and dapsone. METHODS: This was a
prospective, multicentre, randomized, nonblinded clinical trial that compared the
efficacy and safety of two parallel groups of patients with BP treated with oral
methylprednisolone 0.5 mg kg-1 per day in combination with either azathioprine
1.5-2.5 mg kg-1 per day or dapsone 1.5 mg kg-1 per day. Nine German and Austrian
departments of dermatology included 54 patients based on clinical lesions,
positive direct immunofluorescence (IF) microscopy and detection of serum
autoantibodies by indirect IF microscopy, immunoblotting or enzyme-linked
immunosorbent assay. The primary end point was the time until complete tapering
of methylprednisolone, and the most important secondary end point was the
cumulative corticosteroid dose. RESULTS: In eight patients (five azathioprine,
three dapsone), methylprednisolone could be discontinued after a median time of
251 days in the azathioprine group and 81 days in the dapsone group. The median
cumulative corticosteroid dose was 2.65 g for azathioprine compared with 1.92 g
for dapsone (P = 0.06). The median numbers of days when corticosteroids were
applied were 148 and 51, respectively (P = 0.24). No significant difference in
the number of adverse events was seen between the treatment arms. Four patients
(8%) died within the observation period of 12 months. CONCLUSIONS: Due to the
lower than intended number of patients, the results of the primary and secondary
end points were not or only barely significant. Dapsone appeared to have a
moderately higher corticosteroid-sparing potential than azathioprine. The
combination regimen of either drug with oral methylprednisolone is associated
with a relatively low 1-year mortality in this vulnerable patient population.
PMID- 28494098
TI - Core elements to understand and improve coping with Parkinson's disease in
patients and family carers: A focus group study.
AB - AIMS: The aim of this study were: (1) To explore the meaning that coping with
Parkinson's disease has for patients and family carers; (2) To suggest the
components of an intervention focused on enhancing their coping with the disease.
BACKGROUND: Adapting to Parkinson's disease involves going through many difficult
changes; however, it may improve quality of life in patients and family carers.
One of the key aspects for facilitating the psychosocial adjustment to
Parkinson's disease is the strengthening of coping skills. DESIGN: A sequential
explanatory mixed methods study was carried out. Findings from the qualitative
phase are presented. METHODS: Data were collected in May 2014 through three focus
groups: one of people with Parkinson's disease (n = 9), one of family carers (n =
7) and one of healthcare professionals (n = 5). All focus groups were digitally
recorded and transcribed verbatim and content analysis was independently carried
out by two researchers. FINDINGS: The participants coincided in highlighting that
coping with Parkinson's disease helped the patient and the family carer in their
search for balance; and it implied a transformation in their lives. To aid the
process of coping with Parkinson's disease, a multifaceted intervention is
proposed. CONCLUSION: Coping with Parkinson's disease is a complex process for
both patients and family carers and it should therefore be considered a standard
service in healthcare policies aimed at this group. The proposed intervention
constitutes a nursing tool which has great potential to improve the quality of
life in Parkinson's disease and in other long-term conditions.
PMID- 28494099
TI - Prevalence of gestational diabetes mellitus evaluated by universal screening with
a 75-g, 2-hour oral glucose tolerance test and IADPSG criteria.
AB - OBJECTIVE: To determine the prevalence of gestational diabetes mellitus (GDM) and
its association with maternal age among Turkish women diagnosed by International
Association of Diabetes and Pregnancy Study Group (IADPSG) criteria. METHODS: A
cross-sectional study was conducted in 2013-2015 among non-diabetic pregnant
women aged 18-49 years who were universally screened for GDM by IADPSG criteria.
The percentage of women meeting each diagnostic threshold and the prevalence of
GDM by age group were calculated. Linear trends were evaluated by logistic
regression. RESULTS: Among 1434 women screened, 159 (11.1%, 95% confidence
interval 9.5%-12.7%) were diagnosed with GDM; eleven of these women had been
diagnosed according to a fasting glucose level in the first trimester. The
prevalence of GDM was 6.6% (10/151), 7.3% (37/507), 8.8% (42/479), 16.7%
(45/270), and 35.2% (25/71) among women aged younger than 25, 25-29, 30-34, 35
39, and 40 years or older, respectively. GDM prevalence increased with age
(P<0.001). The numbers of women diagnosed with GDM in the second trimester who
exceeded one, two, and three thresholds of the 2-hour oral glucose tolerance test
were 66 (44.6%), 52 (35.1%), and 30 (20.3%), respectively. CONCLUSION: Prevalence
of GDM was correlated with maternal age. Most women diagnosed in the second
trimester exceeded the threshold at only one of the three timepoints.
PMID- 28494100
TI - Paracrine regulation of melanogenesis.
AB - Melanocytes are generally characterized by the basic ability of melanin synthesis
and transfer to adjacent keratinocytes. This constitutes an individual skin
phenotype and provides epidermal protection from various stimuli, such as
ultraviolet irradiation, through a complex process called melanogenesis, which
can be regulated by autocrine or paracrine factors. Recent evidence has revealed
the paracrine effects of keratinocytes on melanogenesis by secreting cytokines,
including alpha-melanocyte stimulating hormone and endothelin-1. In addition to
keratinocytes, there are other types of cells in the skin, such as fibroblasts
and immune cells, which are also actively involved in the regulation of
melanocyte behaviour through the production of paracrine factors. In addition,
extracellular matrix proteins, which are secreted mainly by skin-resident cells,
not only play direct roles in regulating melanocyte morphology and functions but
also provide structural support between the epidermis and dermis to control the
distribution of various secreted cytokines from keratinocytes and/or fibroblasts,
which are potentially involved in the regulation of melanogenesis. Moreover,
understanding the origin of melanocytes (neural crest cells) and the presence of
nerve endings in the epidermis can reveal the intimate contact between
melanocytes and cutaneous specific nervous system proteins. Melanocytes are
associated with all these networks with corresponding receptors expressed on the
cell surface. In this review, we provide an overview of recent advances in
determining the intimate relationships between melanocytes and their surrounding
elements, which provide insights into the complex nature of the regulation of
melanogenesis.
PMID- 28494101
TI - Stability Enhancement of Ocimum Sanctum Linn. Essential Oils Using Stearic Acid
in Aluminum Carboxymethyl Cellulose Film-Coated Gelatin Microcapsules.
AB - Holy basil essential oils (HBEO) can be used in many food applications due to
antioxidant and antimicrobial attributes, but they are susceptible to degradation
upon storage. Therefore, a protective system is required to extend their shelf
life. HBEO was microencapsulated by coacervation using gelatin and the
microcapsules were subsequently coated with stearic acid (1%, 2%, and 3%) in
carboxymethyl cellulose emulsions. The results showed that HBEO contents
decreased with increasing stearic acid concentrations from 76% to 59%. Fourier
transform infrared spectroscopy analysis suggested that HBEO was stable during
microencapsulation. After 3-month storage, changes in appearance were detected in
all samples, especially the uncoated and 3% stearic acid-coated microcapsules.
Additionally, the surface HBEO content increased significantly, consistent with a
distinct increase in darkness and agglomeration. X-ray diffraction analysis
revealed the physical change of microcapsules, attributed to the renaturation of
gelatin and recrystallization of stearic acid. The antioxidant activity of both
non-encapsulated and encapsulated HBEO after storage decreased significantly,
except the microcapsule coated with 1% stearic acid (half maximal inhibitory
concentration of 0.35 mg/mL), whereas the antimicrobial activity remained
constant. The findings suggest that HBEO microcapsules coated with 1% stearic
acid could serve as antioxidant and antimicrobial additives in food industries.
PMID- 28494102
TI - Noninvasive carotid artery elastography using multielement synthetic aperture
imaging: Phantom and in vivo evaluation.
AB - PURPOSE: Vascular elastography can visualize the strain distribution in the
carotid artery, which could be useful in assessing the propensity of advanced
plaques to rupture. In our previous studies, we demonstrated that sparse
synthetic aperture (SA) imaging can produce high quality vascular strain
elastograms. However, the low output power of SA imaging may hamper its clinical
utility. In this study, we hypothesize that multi-element defocused emissions can
overcome this limitation and improve the quality of the vascular strain
elastograms. METHODS: To assess the impact of attenuation on the elastographic
performance of SA and (multi-element synthetic aperture) MSA imaging, we
conducted experiments using heterogeneous vessel phantoms with ideal (0.1 dB cm-1
MHz-1 ) and realistic (0.75 dB cm-1 MHz-1 ) attenuation. Further, we validated
the results of the phantom study in vivo, on a healthy male volunteer. All echo
imaging was performed at a transmit frequency of 5 MHz, using a commercially
available ultrasound scanner (Sonix RP, Ultrasonix Medical Corp., Richmond, BC,
Canada). RESULTS: The results from the phantom results demonstrated that plaques
were visible in all strain elastograms, but those produced using MSA imaging had
less artifacts. MSA imaging improved the elastographic contrast to noise ratio
(CNRe) of the vascular elastograms by 14.58 dB relative to SA imaging, and 9.1 dB
relative to compounded plane wave (CPW) imaging. Further, the results
demonstrated that the elastographic performance of MSA imaging improved with
increase in (a) the number of transmit-receive events and (b) the size of the
transmit sub-aperture, up to 13 elements. Using larger sub-apertures degraded the
elastographic performance. The results from the in vivo study were in good
agreement with the phantom results. Specifically, using a defocused multi-element
transmit sub-aperture for SA imaging improved the performance of vascular
elastography. CONCLUSIONS: The results suggested that MSA imaging can produce
reliable vascular stain elastograms. Future studies will involve using coded
excitations to improve the CNRe and frame-rate of the proposed technique for
vascular elastography.
PMID- 28494103
TI - Recruiting nurses through social media: Effects on employer brand and
attractiveness.
AB - AIM: To investigate whether and how nurses' exposure to a hospital's profile on
social media affects their perceptions of the hospital's brand and attractiveness
as an employer. BACKGROUND: Since in many places across the globe hospitals are
struggling with nursing shortages, competition is rising to be perceived as an
attractive employer by this target group. Organizations are increasingly using
social media for recruitment, however, little is known about its effects on
potential applicants' perceptions of the organization as an employer. We thus
examine whether these effects occur and rely on the media richness theory to
explain the mechanisms at play. DESIGN: A between-subjects experimental design
was applied. Three conditions were used: a control group, one condition that
required visiting the Facebook page of a hospital and one condition that required
visiting the LinkedIn page. METHOD: The focal organization was an existing
Belgian hospital which had a LinkedIn and a Facebook page. An online
questionnaire was sent to nursing students and employed nurses over 5 months in
2015-2016. RESULTS: Nurses' exposure to the hospital's Facebook or LinkedIn page
had a significant positive effect on a majority of the employer brand dimensions,
both instrumental and symbolic. In addition, nurses who visited the Facebook page
felt more attracted to working at the hospital. Most of these effects were
mediated by social presence. CONCLUSION: Nurses' perceptions of employers can be
positively influenced by seeing a hospital's social media page. Hospitals can
thus employ social media to improve their employer brand image and
attractiveness.
PMID- 28494104
TI - Prevalence of metabolic syndrome and its association with lifestyle and
cardiovascular biomarkers among postmenopausal women in western Algeria.
AB - OBJECTIVE: To evaluate the prevalence of metabolic syndrome (MetS), its
components, and their relationship with lifestyle, inflammation, and oxidative
stress among postmenopausal Algerian women. METHODS: A prospective cross
sectional survey was conducted among postmenopausal women at a clinic in Oran,
Algeria, from March 1 to June 28, 2015. A diagnosis of MetS was made using the
National Cholesterol Education Program Adult Treatment Panel III guidelines.
Demographic, clinical, metabolic, inflammatory, dietary, and energy variables
were assessed. RESULTS: Among 183 participants, 106 (57.9%) were diagnosed with
MetS. Components of MetS included hypertension (n=144, 78.7%), hyperglycemia
(n=135, 73.8%), hypertriglyceridemia (n=125, 68.3%), abdominal obesity (n=123,
67.2%), and low levels of high-density lipoprotein cholesterol (n=121, 66.1%).
Although daily energy expenditure was similar among the women with or without
MetS, total energy intake was increased in the group with MetS (P<0.001). The
following measures were also increased among women with MetS: saturated fatty
acid intake (P<0.001), C-reactive protein (P=0.051), thiobarbituric acid reactive
substances (P<0.001), and carbonyls (P<0.001). By contrast, decreased
monounsaturated fatty acid intake (P=0.024) and catalase activity (P<0.001) were
observed in this group. CONCLUSION: Postmenopausal status could predict MetS,
with inflammation and oxidative stress arising from an unhealthy lifestyle
potentially increasing cardiovascular risk.
PMID- 28494105
TI - Empathy in paediatric intensive care nurses part 2: Neural correlates.
AB - AIMS: To determine if there are brain activity differences between paediatric
intensive care nurses and allied health professionals during pain intensity
rating tasks and test whether these differences are related to the population
observed (infant or adult) and professional experience. BACKGROUND: The
underestimation of patients' pain by healthcare professionals has generally been
associated with patterns of change in neural response to vicarious pain, notably
reduced activation in regions associated with affective sharing and increased
activation in regions associated with regulation, compared with controls.
Paediatric nurses, however, have recently been found to provide higher estimates
of infants' pain in comparison to allied health controls, suggesting that changes
in neural response of this population might be different than other health
professionals. DESIGN: Cross-sectional study. METHODS: Functional MRI data were
acquired from September 2014-June 2015 and used to compare changes in brain
activity in 27 female paediatric care nurses and 24 allied health professionals
while rating the pain of infants and adults in a series of video clips. RESULTS:
Paediatric nurses rated infant and adult pain higher than allied health
professionals, but the two groups' neural response only differed during
observation of infant pain; paediatric nurses mainly showed significantly less
activation in the medial prefrontal cortex (linked to cognitive empathy) and in
the left anterior insula and inferior frontal cortex (linked to affective
sharing). CONCLUSIONS: Patterns of neural activity to vicarious pain may vary
across healthcare professions and patient populations and the amount of
professional experience might explain part of these differences.
PMID- 28494106
TI - Closed-loop control of compression paddle motion to reduce blurring in
mammograms.
AB - BACKGROUND: Since the introduction of full field digital mammography (FFDM) a
large number of UK breast cancer screening centers have reported blurred images,
which can be caused by movement at the compression paddle during image
acquisition. PURPOSE: To propose and investigate the use of position feedback
from the breast side of the compression paddle to reduce the settling time of
breast side motion. METHOD: Movement at the breast side of the paddle was
measured using two calibrated linear potentiometers. A mathematical model for the
compression paddle, machine drive, and breast was developed using the paddle
movement data. Simulation software was used to optimize the position feedback
controller parameters for different machine drive time constants and simulate the
potential performance of the proposed system. RESULTS: The results obtained are
based on simulation alone and indicate that closed-loop control of breast side
paddle position dramatically reduced the settling time from over 90 s to less
than 4 s. The effect of different machine drive time constants on the open-loop
response is insignificant. With closed-loop control, the larger the time constant
the longer the time required for the breast side motion to settle. CONCLUSIONS:
Paddle motion induced blur could be significantly reduced by implementing the
proposed closed-loop control.
PMID- 28494107
TI - Recommendation to test limonene hydroperoxides 0.3% and linalool hydroperoxides
1.0% in the British baseline patch test series.
AB - BACKGROUND: There is a significant rate of sensitization worldwide to the
oxidized fragrance terpenes limonene and linalool. Patch testing to oxidized
terpenes is not routinely carried out; the ideal patch test concentration is
unknown. OBJECTIVES: To determine the best test concentrations for limonene and
linalool hydroperoxides, added to the British baseline patch test series, to
optimize detection of true allergy and to minimize irritant reactions. METHODS:
During 2013-2014, 4563 consecutive patients in 12 U.K. centres were tested to
hydroperoxides of limonene in petrolatum (pet.) 0.3%, 0.2% and 0.1%, and
hydroperoxides of linalool 1.0%, 0.5% and 0.25% pet. Irritant reactions were
recorded separately from doubtful reactions. Concomitant reactions to other
fragrance markers and clinical relevance were documented. RESULTS: Limonene
hydroperoxide 0.3% gave positive reactions in 241 (5.3%) patients, irritant
reactions in 93 (2.0%) and doubtful reactions in 110 (2.4%). Linalool
hydroperoxide 1.0% gave positive reactions in 352 (7.7%), irritant reactions in
178 (3.9%) and doubtful reactions in 132 (2.9%). A total of 119 patients with
crescendo reactions to 0.3% limonene would have been missed if only tested with
0.1% and 131 patients with crescendo reactions to 1.0% linalool would have been
missed if only tested with 0.25%. In almost two-thirds of patients with positive
patch tests to limonene and linalool the reaction was clinically relevant. The
majority of patients did not react to any fragrance marker in the baseline
series. CONCLUSIONS: We recommend that limonene hydroperoxides be tested at 0.3%
and linalool hydroperoxides at 1.0% in the British baseline patch test series.
PMID- 28494109
TI - Oncology Drug Dosing in Gilbert Syndrome Associated with UGT1A1: A Summary of the
Literature.
AB - Gilbert syndrome (GS) is a hereditary condition that affects ~10% of the
population. It is characterized by intermittent, unconjugated hyperbilirubinemia
in the absence of hepatocellular damage and hemolysis. Although GS is often
described as a benign laboratory finding, it may alter drug metabolism by
decreasing the ability to conjugate drugs. Genetic polymorphisms, specifically
the UGT1A1*28 allele, may reduce glucuronidation by 30% that severely impacts the
ability to metabolize certain medications. Antineoplastic agents used in
oncologic settings have toxic side effects, and alterations in metabolism may
result in severe or even life-threatening toxicities. Many of the drug monographs
provided by manufacturers contain dose adjustment parameters for hepatic
function, using serum bilirubin as a surrogate marker. However, in patients with
GS, hepatic function remains normal in the setting of hyperbilirubinemia, and
scant literature is available to provide guidance on empirical dosage adjustment.
In this review, we conducted a literature search of routinely used oncology
medications and assessed the need for empirical dose adjustments in the setting
of GS.
PMID- 28494110
TI - Computerized detection of lung nodules through radiomics.
AB - PURPOSE: Lung cancer is a major cause of cancer deaths, and the 5-year survival
rate of stage IV lung cancer patients is only 2%. However, the 5-year survival
rate of stage I lung cancer patients significantly increases to 50%. As such,
spiral computed tomography (CT) scans are necessary to diagnose high-risk lung
cancer patients in early stages. In this study, a computer-aided detection (CAD)
system with radiomics was proposed. This system could automatically detect
pulmonary nodules and reduce radiologists' workloads and human errors. METHODS:
In the proposed scheme, a nodular enhancement filter was used to segment nodule
candidates and extract radiomic features. A synthetic minority over-sampling
technique was also applied to balance the samples, and a random forest method was
utilized to distinguish between real nodules and false positive detections. The
radiomics approach quantified intratumor heterogeneity and multifrequency
information, which are highly correlated with lung nodules. RESULTS: The proposed
method was used to evaluate 1004 CT cases from the well-known Lung Image Database
Consortium, and 88.9% sensitivity with four false positive detections per CT scan
was obtained by randomly selecting 502 cases for training and 502 other cases for
testing. CONCLUSIONS: The proposed scheme yielded a high performance on the LIDC
database. Therefore, the proposed scheme is possibly effective for various CT
configurations used in routine diagnosis and lung cancer screening.
PMID- 28494108
TI - Selective kappa receptor partial agonist HS666 produces potent antinociception
without inducing aversion after i.c.v. administration in mice.
AB - BACKGROUND AND PURPOSE: The kappa receptor has a central role in modulating
neurotransmission in central and peripheral neuronal circuits that subserve pain
and other behavioural responses. Although kappa receptor agonists do not produce
euphoria or lead to respiratory suppression, they induce dysphoria and sedation.
We hypothesized that brain-penetrant kappa receptor ligands possessing biased
agonism towards G protein signalling over beta-arrestin2 recruitment would
produce robust antinociception with fewer associated liabilities. EXPERIMENTAL
APPROACH: Two new diphenethylamines with high kappa receptor selectivity, HS665
and HS666, were assessed following i.c.v. administration in mouse assays of
antinociception with the 55 degrees C warm-water tail withdrawal test, locomotor
activity in the rotorod and conditioned place preference. The [35 S]-GTPgammaS
binding and beta-arrestin2 recruitment in vitro assays were used to characterize
biased agonism. KEY RESULTS: HS665 (kappa receptor agonist) and HS666 (kappa
receptor partial agonist) demonstrated dose-dependent antinociception after
i.c.v. administration mediated by the kappa receptor. These highly selective
kappa receptor ligands displayed varying biased signalling towards G protein
coupling in vitro, consistent with a reduced liability profile, reflected by
reduced sedation and absence of conditioned place aversion for HS666. CONCLUSIONS
AND IMPLICATIONS: HS665 and HS666 activate central kappa receptors to produce
potent antinociception, with HS666 displaying pharmacological characteristics of
a kappa receptor analgesic with reduced liability for aversive effects
correlating with its low efficacy in the beta-arrestin2 signalling pathway. Our
data provide further understanding of the contribution of central kappa receptors
in pain suppression, and the prospect of dissociating the antinociceptive effects
of HS665 and HS666 from kappa receptor-mediated adverse effects.
PMID- 28494111
TI - Evaluation of indicated non-cosmetic panniculectomy at time of gynecologic
surgery.
AB - OBJECTIVE: To report postoperative outcomes among patients undergoing indicated
non-cosmetic panniculectomy at the time of gynecologic surgery. METHODS: Medical
charts were retrospectively reviewed for patients who underwent panniculectomy
coupled with gynecologic surgery at a university-affiliated hospital in the USA
in 1990-2014. The data reviewed included age, body mass index (BMI, calculated as
weight in kilograms divided by the square of height in meters), surgical
procedure, estimated blood loss, pathology, wound complication, diabetes,
hypertension, smoking, and readmission rate. One-way analysis of variance and
logistic regression were used to evaluate the data. RESULTS: In total, 300
patients underwent panniculectomy; the mean age was 51 years and the mean BMI was
46. Overall, there were 94 (31.3%) complications, including 85 (28.3%) cases of
superficial cellulitis and 9 (3.0%) cases of surgical-site infection. In logistic
regression, diabetes, hypertension, and smoking were significant predictors of
wound complications, identifying 78% of women who subsequently developed wound
complications. CONCLUSION: Panniculectomy combined with gynecologic surgery was
found to be safe and effective for obese patients, with an acceptable incidence
of wound infection. History of diabetes, hypertension, and smoking increased the
risk of postoperative wound complications. These factors will help to predict
patients at risk of wound complication.
PMID- 28494113
TI - The diagnostic conundrum of bacterial infections in cirrhotic patients.
PMID- 28494112
TI - Using the Lewis Acid Me3 Si-F-Al(ORF )3 To Prepare Phosphino-Phosphonium Cations
with the Least-Coordinating Anion [(RF O)3 Al-F-Al(ORF )3 ].
AB - By reaction of two equivalents of Me3 Si-F-Al(ORF )3 1 with an equimolar amount
of PPh2 Cl, the salt [Ph2 P-PPh2 Cl]+ [(RF O)3 Al-F-Al(ORF )3 ]- 2 is prepared
smoothly in 91 % yield (NMR, XRD). The synthesis of [Ph2 P-PPh3 ]+ [(RF O)3 Al-F
Al(ORF )3 ]- 3 is best achieved by a two-step reaction: first, two equivalents of
1 react with one PPh3 to give [Me3 Si-PPh3 ]+ [(RF O)3 Al-F-Al(ORF )3 ]- 4 (NMR,
XRD), which, upon reaction with PPh2 Cl, yields pure 3 and Me3 SiCl (NMR, XRD).
Typically, a stoichiometry of two equivalents of 1 with respect to one equivalent
of the chloride donor should be used. Otherwise, the residual strong Lewis
acidity of the [(RF O)3 Al-F-Al(ORF )3 ]- anion in the presence of the [F-Al(ORF
)3 ]- anion-that forms with less than two equivalents of 1-leads to further
chloride exchange reactions that complicate work-up. This route presents the
easiest way to introduce the least-coordinating [(RF O)3 Al-F-Al(ORF )3 ]- anion
into a system. We expect a wide use of this route in all areas, in which chloride
bond heterolysis in combination with very weakly coordinating anions is
desirable. Additionally, we performed calculations on the bond dissociation
mechanisms of [R2 P-PMe3 ]+ and the isoelectronic Me2 P-SiMe3 and Me2 Si-PMe3 in
dependence of the solvent permittivity. These calculations show, especially for
the neutral reference compounds, a heavy influence of the solvent on the
dissociation mechanism, which is why we suggest investigating these properties in
solution instead of gas phase.
PMID- 28494114
TI - A Sustainable Redox-Flow Battery with an Aluminum-Based, Deep-Eutectic-Solvent
Anolyte.
AB - Nonaqueous redox-flow batteries are an emerging energy storage technology for
grid storage systems, but the development of anolytes has lagged far behind that
of catholytes due to the major limitations of the redox species, which exhibit
relatively low solubility and inadequate redox potentials. Herein, an aluminum
based deep-eutectic-solvent is investigated as an anolyte for redox-flow
batteries. The aluminum-based deep-eutectic solvent demonstrated a significantly
enhanced concentration of circa 3.2 m in the anolyte and a relatively low redox
potential of 2.2 V vs. Li+ /Li. The electrochemical measurements highlight that a
reversible volumetric capacity of 145 Ah L-1 and an energy density of 189 Wh L-1
or 165 Wh kg-1 have been achieved when coupled with a I3- /I- catholyte. The
prototype cell has also been extended to the use of a Br2 -based catholyte,
exhibiting a higher cell voltage with a theoretical energy density of over 200 Wh
L-1 . The synergy of highly abundant, dendrite-free, multi-electron-reaction
aluminum anodes and environmentally benign deep-eutectic-solvent anolytes reveals
great potential towards cost-effective, sustainable redox-flow batteries.
PMID- 28494115
TI - Disentangling species and functional group richness effects on soil N cycling in
a grassland ecosystem.
AB - Species richness (SR) and functional group richness (FGR) are often confounded in
both observational and experimental field studies of biodiversity and ecosystem
function. This precludes discernment of their separate influences on ecosystem
processes, including nitrogen (N) cycling, and how those influences might be
moderated by global change factors. In a 17-year field study of grassland
species, we used two full factorial experiments to independently vary SR (one or
four species, with FGR = 1) and FGR (1-4 groups, with SR = 4) to assess SR and
FGR effects on ecosystem N cycling and its response to elevated carbon dioxide
(CO2 ) and N addition. We hypothesized that increased plant diversity (either SR
or FGR) and elevated CO2 would enhance plant N pools because of greater plant N
uptake, but decrease soil N cycling rates because of greater soil carbon inputs
and microbial N immobilization. In partial support of these hypotheses,
increasing SR or FGR (holding the other constant) enhanced total plant N pools
and decreased soil nitrate pools, largely through higher root biomass, and
increasing FGR strongly reduced mineralization rates, because of lower root N
concentrations. In contrast, increasing SR (holding FGR constant and despite
increasing total plant C and N pools) did not alter root N concentrations or net
N mineralization rates. Elevated CO2 had minimal effects on plant and soil N
metrics and their responses to plant diversity, whereas enriched N increased
plant and soil N pools, but not soil N fluxes. These results show that functional
diversity had additional effects on both plant N pools and rates of soil N
cycling that were independent of those of species richness.
PMID- 28494116
TI - Randomised clinical study of plaque removal efficacy of a power toothbrush in a
paediatric population.
AB - BACKGROUND: Clinical investigations of plaque removal efficacy of power
toothbrushes in children are limited. AIM: To compare plaque removal of a power
versus manual toothbrush in a paediatric population. DESIGN: This was a
randomised, replicate-use, single-brushing, examiner-blinded, two-treatment, four
period crossover clinical trial in children 8-11 years of age. Subjects were
randomly assigned to a treatment sequence involving an oscillating-rotating power
toothbrush and a manual toothbrush control. Subjects brushed under supervision
with a NaF dentifrice. Plaque was assessed pre- (baseline) and post-brushing
using the Turesky Modification of the Quigley-Hein Plaque Index by two examiners.
Plaque scores were averaged for mixed and permanent dentition on a per-subject
basis and analysed using a mixed-model ancova for a crossover design. RESULTS:
Forty-one subjects (mean 9.0 years) were randomised and completed the trial. Both
the power brush and manual brush provided statistically significant mean plaque
reductions versus baseline in all analyses (P < 0.001). For both examiners,
plaque removal was significantly (P < 0.001) larger for the power brush in
permanent and mixed dentitions. The interexaminer correlations for the permanent
dentition were strong (ICC = 0.68-0.88) for pre-brushing plaque across all
periods. CONCLUSIONS: An oscillating-rotating power toothbrush provided superior
plaque reduction versus a manual toothbrush in children.
PMID- 28494117
TI - Something old, something new, something borrowed, something green.
PMID- 28494118
TI - Objective automated quantification of fluorescence signal in histological
sections of rat lens.
AB - Visual quantification and classification of fluorescent signals is the gold
standard in microscopy. The purpose of this study was to develop an automated
method to delineate cells and to quantify expression of fluorescent signal of
biomarkers in each nucleus and cytoplasm of lens epithelial cells in a
histological section. A region of interest representing the lens epithelium was
manually demarcated in each input image. Thereafter, individual cell nuclei
within the region of interest were automatically delineated based on watershed
segmentation and thresholding with an algorithm developed in MatlabTM.
Fluorescence signal was quantified within nuclei, cytoplasms and juxtaposed
backgrounds. The classification of cells as labelled or not labelled was based on
comparison of the fluorescence signal within cells with local background. The
classification rule was thereafter optimized as compared with visual
classification of a limited dataset. The performance of the automated
classification was evaluated by asking 11 independent blinded observers to
classify all cells (n = 395) in one lens image. Time consumed by the automatic
algorithm and visual classification of cells was recorded. On an average, 77% of
the cells were correctly classified as compared with the majority vote of the
visual observers. The average agreement among visual observers was 83%. However,
variation among visual observers was high, and agreement between two visual
observers was as low as 71% in the worst case. Automated classification was on
average 10 times faster than visual scoring. The presented method enables
objective and fast detection of lens epithelial cells and quantification of
expression of fluorescent signal with an accuracy comparable with the variability
among visual observers. (c) 2017 International Society for Advancement of
Cytometry.
PMID- 28494119
TI - Noncovalent Interactions between Dopamine and Regular and Defective Graphene.
AB - The role of noncovalent interactions in the adsorption of biological molecules on
graphene is a subject of fundamental interest regarding the use of graphene as a
material for sensing and drug delivery. The adsorption of dopamine on regular
graphene and graphene with monovacancies (GV) is theoretically studied within the
framework of density functional theory. Several adsorption modes are considered,
and notably those in which the dopamine molecule is oriented parallel or quasi
parallel to the surface are the more stable. The adsorption of dopamine on
graphene implies an attractive interaction of a dispersive nature that competes
with Pauli repulsion between the occupied pi orbitals of the dopamine ring and
the pi orbitals of graphene. If dopamine adsorbs at the monovacancy in the A-B
stacking mode, a hydrogen bond is produced between one of the dopamine hydroxy
groups and one carbon atom around the vacancy. The electronic charge
redistribution due to adsorption is consistent with an electronic drift from the
graphene or GV surface to the dopamine molecule.
PMID- 28494121
TI - Biomimetic Total Synthesis of (+/-)-Homodimericin A.
AB - A biomimetic total synthesis of racemic homodimericin A was achieved in seven
steps, including two cascade reactions. Aqueous buffer solutions are found to
help both the oxidative dimerization cascade and the intramolecular Diels-Alder
cascade. This synthetic sequence validates key steps in the biogenetic proposal
of homodimericin A.
PMID- 28494120
TI - Posttraumatic stress disorder symptom severity is associated with reduced default
mode network connectivity in individuals with elevated genetic risk for
psychopathology.
AB - BACKGROUND: Accumulating evidence suggests that posttraumatic stress disorder
(PTSD) is associated with disrupted default mode network (DMN) connectivity, but
findings across studies have not been uniform. Individual differences in relevant
genes may account for some of the reported variability in the relationship
between DMN connectivity and PTSD. In this study, we investigated this
possibility using genome-wide association study (GWAS) derived polygenic risk
scores (PRSs) for relevant psychiatric traits. We hypothesized that the
association between PTSD and DMN connectivity would be moderated by genetic risk
for one or more psychiatric traits such that individuals with elevated polygenic
risk for psychopathology and severe PTSD would exhibit disrupted DMN
connectivity. METHODS: Participants were 156 white, non-Hispanic veterans of the
wars in Iraq and Afghanistan who were genotyped and underwent resting state
functional magnetic resonance imaging and clinical assessment. PRSs for
neuroticism, anxiety, major depressive disorder, and cross-disorder risk (based
on five psychiatric disorders) were calculated using summary statistics from
published large-scale consortia-based GWASs. RESULTS: Cross-disorder polygenic
risk influenced the relationship between DMN connectivity and PTSD symptom
severity such that individuals at greater genetic risk showed a significant
negative association between PTSD symptom severity and connectivity between the
posterior cingulate cortex and right middle temporal gyrus. Polygenic risk for
neuroticism, anxiety, and major depressive disorder did not influence DMN
connectivity directly or through an interaction with PTSD. CONCLUSIONS: Findings
illustrate the potential power of genome-wide PRSs to advance understanding of
the relationship between PTSD and DMN connectivity, a putative neural
endophenotype of the disorder.
PMID- 28494122
TI - Comprehensive database of Manufactured Gas Plant tars. Part B. Aliphatic and
aromatic compounds.
AB - RATIONALE: Coal tars are a mixture of organic and inorganic compounds that were
produced as a by-product from the manufactured gas and coke making industries.
The composition of the tar produced varies depending on many factors; these
include the temperature of production and the type of retort used. As different
production processes produce different tars, a comprehensive database of the
compounds present within coal tars from different production processes is a
valuable resource. Such a database would help to understand how their chemical
properties differ and what hazards the compounds present within these tars might
pose. This study focuses on the aliphatic and aromatic compounds present in a
database of 16 different tars from five different production processes. METHODS:
Samples of coal tar were extracted using accelerated solvent extraction (ASE) and
derivatised post-extraction using N,O-bis(trimethylsilyl)trifluoroacetamide
(BSTFA) with 1% trimethylchlorosilane (TMCS). The derivatised samples were
analysed using two-dimensional gas chromatography combined with time-of-flight
mass spectrometry (GCxGC/TOFMS). RESULTS: A total of 198 individual aliphatic and
951 individual aromatic compounds were detected within 16 tar samples produced by
five different production processes. The polycyclic aromatic hydrocarbon (PAH)
content of coal tars varies greatly depending on the production process used to
obtain the tars and this is clearly demonstrated within the results. The
aliphatic composition of the tars provided an important piece of analytical
information that would have otherwise been missed with the detection of
petrogenic compounds such as alkyl cyclohexanes. CONCLUSIONS: The aromatic
compositions of the tar samples varied greatly between the different production
processes investigated and useful analytical information was obtained about the
individual production process groups. Alkyl cyclohexanes were detected in all
samples from sites known to operate Carbureted Water Gas plants and not detected
in those that did not. This suggests that petrogenic material may be expected at
many UK gaswork sites.
PMID- 28494123
TI - Ecological momentary interventions for depression and anxiety.
AB - Ecological momentary interventions (EMIs) are becoming more popular and more
powerful resources for the treatment and prevention of depression and anxiety due
to advances in technological capacity and analytic sophistication. Previous work
has demonstrated that EMIs can be effective at reducing symptoms of depression
and anxiety as well as related outcomes of stress and at increasing positive
psychological functioning. In this review, we highlight the differences between
EMIs and other forms of treatment due to the nature of EMIs to be deeply
integrated into the fabric of people's day-to-day lives. EMIs require unique
considerations in their design, deployment, and evaluation. Furthermore, given
that EMIs have been advanced by changes in technologies and that the use of
behavioral intervention technologies for mental health has been increasing, we
discuss how technologies and analytics might usher in a new era of EMIs. Future
EMIs might reduce user burden and increase intervention personalization and
sophistication by leveraging digital sensors and advances in natural language
processing and machine learning. Thus, although current EMIs are effective, the
EMIs of the future might be more engaging, responsive, and adaptable to different
people and different contexts.
PMID- 28494124
TI - Professor Crispian Scully CBE, DSc, DChD, DMed (HC), Dhc (multi), MD, PhD, PhD
(HC), FMedSci, MDS, MRCS, BSc, FDSRCS, FDSRCPS, FFDRCSI, FDSRCSEd FRCPath, FHEA
(1945-2017).
PMID- 28494125
TI - Harassment and Mental Distress Among Adolescent Female Students by Sexual
Identity and BMI or Perceived Weight Status.
AB - OBJECTIVE: Sexual minority girls (lesbian/bisexual) and girls with
overweight/obesity experience high rates of discrimination and mental distress.
This study explored whether BMI or perceived weight status might compound sexual
minority girls' risk for harassment and mental distress. METHODS: Data on female
students from the national 2015 Youth Risk Behavior Survey (n = 7,006) were
analyzed. Logistic regression was used to examine differences in bullying,
harassment, and mental distress across sexual identity/BMI groups:
heterosexual/normal-weight, heterosexual/overweight, sexual minority/normal
weight, and sexual minority/overweight. Procedures were repeated with four
analogous groups created from sexual identity and perceived weight. RESULTS:
Across sexual identity/BMI groups, being overweight increased heterosexual
females' odds of being bullied or experiencing suicidal thoughts and behaviors.
Regardless of weight status, sexual minority females had greater odds for each
outcome than heterosexual females. Sexual minority females who perceived
themselves as overweight had greater odds of suicidality than all other sexual
minority/perceived weight groups. CONCLUSIONS: Double jeopardy may exist for
sexual minority female students who perceive themselves as overweight.
Professional development with school staff on how to create a positive climate
for sexual minorities and those with overweight/obesity and addressing positive
identity and body image within school-based suicide prevention efforts may be
important to the well-being of adolescent girls.
PMID- 28494127
TI - Does iron reduction control the release of dissolved organic carbon and phosphate
at catchment scales? Need for a joint research effort.
AB - Increasing concentrations of dissolved iron and DOC are likely linked to
decreasing nitrogen depositon.
PMID- 28494128
TI - Alcohol consumption, cigarette smoking and incidence of aortic valve stenosis.
AB - BACKGROUND: Alcohol consumption and cigarette smoking are modifiable lifestyle
factors with important impact on public health. It is unclear whether these
factors influence the risk of aortic valve stenosis (AVS). OBJECTIVE: To
investigate the associations of alcohol consumption and smoking, including
smoking intensity and time since cessation, with AVS incidence in two prospective
cohorts. METHODS: This analysis was based on data from the Swedish Mammography
Cohort and the Cohort of Swedish Men, comprising 69 365 adults without
cardiovascular disease at baseline. Participants were followed for AVS incidence
and death by linkage to the Swedish National Patient and Causes of Death
Registers. Hazard ratios (HR) with 95% confidence intervals (CI) were estimated
by Cox proportional hazards regression. RESULTS: Over a mean follow-up of 15.3
years, 1249 cases of AVS (494 in women and 755 in men) were recorded. Compared
with never drinkers of alcohol (lifelong abstainers), the risk of AVS was
significantly lower in current light drinkers (1-6 drinks per week [1 drink = 12
g alcohol]; multivariable HR 0.82; 95% CI: 0.68-0.99). The risk of AVS increased
with increasing smoking intensity. Compared with never smokers, the HR was 1.46
(95% CI: 1.16-1.85) in current smokers of >=30 pack-years. Former smokers who had
quit smoking 10 or more years previously had similar risk for AVS as never
smokers. CONCLUSIONS: This study suggests that current light alcohol consumption
is associated with a lower risk of AVS, and indicates that the association
between smoking and AVS risk is reversible.
PMID- 28494126
TI - Real-life glycemic control in patients with type 2 diabetes treated with insulin
therapy: A prospective, longitudinal cohort study (Diabetes Distress and Care
Registry at Tenri [DDCRT 9]).
AB - AIMS/INTRODUCTION: We investigated the association between four insulin regimens,
and increase in glycated hemoglobin (HbA1c) and insulin dose in a real-life
clinical setting because there are no data about them among insulin regimens.
MATERIALS AND METHODS: Participants included 757 patients with type 2 diabetes
having been treated with insulin therapy for more than 1 year. The four insulin
regimens were regimen 1 (long-acting insulin, once daily), regimen 2 (biphasic
insulin, twice daily), regimen 3 (biphasic insulin, three times daily) and
regimen 4 (basal-bolus therapy). Main outcomes were increases in HbA1c levels
>0.5% and increases in daily insulin units after 1 year. We carried out
multivariable analyses to examine differences in glycemic control and insulin
dose with adjustment for possible confounders. RESULTS: Mean HbA1c level and
duration of insulin therapy were 7.8% and 11.3 years, respectively. HbA1c levels
increased by >0.5% at follow up in 22.8, 24.9, 20.7, and 29.3% of participants
using regimen 1, 2, 3 and 4, respectively, with no significant differences
between groups. Daily insulin doses increased in 62.3, 68.8, 65.3 and 38.6% of
patients, respectively (P < 0.001). Multivariable regression analysis showed that
patients who received regimen 4 had significantly lower odds of requiring future
insulin dose increases than those who had received regimen 2 (adjusted odds ratio
0.24, 95% confidence interval 0.14-0.41; P < 0.001). CONCLUSIONS: Many patients
receiving insulin therapy showed increases in HbA1c levels and insulin doses 1
year later. The smallest increase in insulin dose was observed in the basal-bolus
therapy group compared with other regimens.
PMID- 28494129
TI - When trust is threatened: Qualitative study of parents' perspectives on
problematic clinical relationships in child cancer care.
AB - OBJECTIVE: We explored parents' accounts of the parent-clinician relationship in
childhood cancer to understand how parents who perceive threats to the
relationship can be supported. METHODS: Multicentre longitudinal qualitative
study, with 67 UK parents of children (aged 1-12 years) receiving treatment for
acute lymphoblastic leukaemia. Analyses drew on the wider sample but focussed on
50 semistructured interviews with 20 parents and were informed by constant
comparison. RESULTS: All 20 parents described problems with clinical care such as
inadequate information or mistakes by staff but varied in how much the problems
threatened their sense of relationship with clinicians. Some parents saw the
problems as having no relevance to the parent-clinician relationship. Others saw
the problems as threats to the clinical relationship but worked to "contain" the
threat in ways that preserved a trusting relationship with at least one senior
clinician. Parents' containment work protected the security they needed from the
parent-clinician relationship, but containment was a tenuous process for some. A
few parents were unable to contain the problems at all; lacking trust in
clinicians, these parents suffered considerably. CONCLUSIONS: Given the
complexity of childhood cancer care, problems with clinical care are inevitable.
By engaging in containment work, parents met their needs to feel secure in the
face of these problems, but the extent to which parents should have to do this
work is debatable. Parents could benefit from support to seek help when problems
arise which threaten their trust in clinicians. Attachment theory can guide
clinicians in giving this support.
PMID- 28494130
TI - Visualization of stereoscopic anatomic models of the paranasal sinuses and
cervical vertebrae from the surgical and procedural perspective.
AB - Recent improvements in three-dimensional (3D) virtual modeling software allows
anatomists to generate high-resolution, visually appealing, colored, anatomical
3D models from computed tomography (CT) images. In this study, high-resolution CT
images of a cadaver were used to develop clinically relevant anatomic models
including facial skull, nasal cavity, septum, turbinates, paranasal sinuses,
optic nerve, pituitary gland, carotid artery, cervical vertebrae, atlanto-axial
joint, cervical spinal cord, cervical nerve root, and vertebral artery that can
be used to teach clinical trainees (students, residents, and fellows) approaches
for trans-sphenoidal pituitary surgery and cervical spine injection procedure.
Volume, surface rendering and a new rendering technique, semi-auto-combined, were
applied in the study. These models enable visualization, manipulation, and
interaction on a computer and can be presented in a stereoscopic 3D virtual
environment, which makes users feel as if they are inside the model. Anat Sci
Educ 10: 598-606. (c) 2017 American Association of Anatomists.
PMID- 28494132
TI - Issue Information - ToC.
PMID- 28494131
TI - Neuropsychological functioning in college students who misuse prescription
stimulants.
AB - BACKGROUND AND OBJECTIVES: Relatively little is known about the
neuropsychological profiles of college students who misuse prescription stimulant
medications. METHODS: Data presented are from college students aged 18-28 years
who misused prescription stimulants prescribed for attention
deficit/hyperactivity disorder and controls (no prescription stimulant misuse).
Students were assessed neuropsychologically using the self-report Behavioral
Rating Inventory of Executive Functioning (BRIEF-A), the Cambridge Automated
Neuropsychological Test and Battery (CANTAB), and other tests of cognitive
functioning. The analyses included 198 controls (age 20.7 +/- 2.6 years) and 100
prescription stimulant misusers (age 20.7 +/- 1.7 years). RESULTS: On the BRIEF
A, misusers were more likely than controls to endorse greater dysfunction on 8 of
12 measures including Inhibition, Self Monitor, Initiation, Working Memory, and
Plan/Organize, when adjusting for race and sex (all p's < .05). Similarly, when
dichotomizing the BRIEF-A as abnormal (T score >= 65), misusers had more
abnormalities on five of nine subscales, as well as all major indices (p's <
.05). Misusers also performed worse on several subtests of the CANTAB and
standardized cognitive battery (p's < .05). A proxy of prescription stimulant
misuse frequency was positively correlated with greater executive dysfunction on
the BRIEF-A. DISCUSSION AND CONCLUSIONS: These data demonstrate elevated risk for
neuropsychological dysfunction among students who misuse prescription stimulants
compared to non-misusing peers. The presence of ADHD contributed significantly to
these cognitive findings. Students who misuse prescription stimulants should be
screened for neuropsychological dysfunction. SCIENTIFIC SIGNIFICANCE: These data
may better elucidate the neuropsychological profile of college-aged prescription
stimulant misusers. (Am J Addict 2017;26:379-387).
PMID- 28494134
TI - Issue Information - Editorial Board.
PMID- 28494133
TI - Interaction between ADH1B*3 and alcohol-facilitating social environments in
alcohol behaviors among college students of african descent.
AB - BACKGROUND AND OBJECTIVES: Although alcohol-facilitating social environmental
factors, such as alcohol offers and high perceived peer drinking norms, have been
extensively studied as determinants of college drinking, their role among college
students of African descent remains understudied. Furthermore, gene-environment
interaction research suggests that the effects of alcohol-facilitating
environments may differ as a function of genetic factors. Specifically, the
alcohol dehydrogenase gene's ADH1B*3 allele, found almost exclusively in persons
of African descent, may modulate the association of risky social environments
with alcohol behaviors. The current study examined whether the ADH1B*3 allele
attenuated the relationship between alcohol-facilitating environments (ie,
alcohol offers and perceived peer drinking norms) and alcohol behaviors. METHOD:
Participants were 241 undergraduate students who self-identified as being of
African descent (mean age = 20 years [SD = 4.11]; 66% female). RESULTS:
Significant interaction effects of ADH1B*3 with alcohol offers were found on
alcohol use frequency (incidence rate ratio [IRR] = 1.14) and on drinking
consequences (IRR = 1.21). ADH1B*3 also interacted with perceived peer norms on
drinking consequences (IRR = 1.41). Carriers of the ADH1B*3 allele drank less
frequently and experienced fewer negative consequences than non-carriers when
exposed to lower levels of alcohol offers and perceived peer drinking. In
contrast, in high alcohol-facilitating environments, no protective genetic effect
was observed. DISCUSSION AND CONCLUSION: This study demonstrates that ADH1B*3 may
protect college students of African descent against alcohol outcomes, although
only in low alcohol-facilitating environments. SCIENTIFIC SIGNIFICANCE: Findings
add to the growing body of knowledge regarding genetic and social determinants of
alcohol behaviors among college students of African descent. (Am J Addict
2017;26:349-356).
PMID- 28494135
TI - Prospective association between body mass index at midlife and healthy aging
among French adults.
AB - OBJECTIVE: To assess the association between midlife body mass index (BMI) and
healthy aging (HA) in the French SU.VI.MAX cohort. METHODS: HA was assessed in
2007 to 2009 among 2,733 individuals, aged 45 to 60 years and free of diabetes,
cardiovascular disease and cancer at baseline (1994-1995). HA was defined as not
developing any major chronic disease, good physical and cognitive functioning, no
limitations in instrumental activities of daily living, no depressive symptoms,
no health-related limitations in social life, good overall self-perceived health,
and no function-limiting pain. Associations between anthropometric indicators
(measured in 1995-1996) and HA were assessed using robust-error-variance Poisson
regression. RESULTS: After adjustment for potential confounders, BMI (continuous)
was negatively associated with HA: relative risk (RR) = 0.97 (95% confidence
interval = 0.96-0.99). Moreover, the detrimental role of obesity (RRobesity vs.
normal weight = 0.67 [0.51-0.88]) was substantially stronger than that of
overweight (RRoverweight vs. normal weight = 0.91 [0.81-1.01]). Furthermore,
while metabolically healthy individuals with overweight had a similar HA
probability as metabolically healthy individuals with normal weight,
metabolically unhealthy overweight individuals had a substantially lowered HA
probability. CONCLUSIONS: This study provides novel evidence that an elevated BMI
at midlife may jeopardize the preservation of health during aging. Our results
also highlight the importance of maintaining a healthy metabolic profile during
midlife.
PMID- 28494136
TI - Effects of an abbreviated obesity intervention supported by mobile technology:
The ENGAGED randomized clinical trial.
AB - OBJECTIVE: To determine the effects on weight loss of three abbreviated
behavioral weight loss interventions with and without coaching and mobile
technology. METHODS: A randomized controlled efficacy study of three 6-month
weight loss treatments was conducted in 96 adults with obesity: 1) self-guided
(SELF), 2) standard (STND), or 3) technology-supported (TECH). STND and TECH
received eight in-person group treatment sessions. SELF and STND used paper
diaries to self-monitor diet, activity, and weight; TECH used a smartphone
application with social networking features and wireless accelerometer. RESULTS:
Weight loss was greater for TECH and STND than SELF at 6 months (-5.7 kg [95%
confidence interval: -7.2 to -4.1] vs. -2.7 kg [95% confidence interval: -5.1 to
0.3], P < 0.05) but not 12 months. TECH and STND did not differ except that more
STND (59%) than TECH (34%) achieved >= 5% weight loss at 6 months (P < 0.05).
Self-monitoring adherence was greater in TECH than STND (P < 0.001), greater in
both interventions than SELF (P < 0.001), and covaried with weight loss (r(84) =
0.36-0.51, P < 0.001). CONCLUSIONS: Abbreviated behavioral counseling can produce
clinically meaningful weight loss regardless of whether self-monitoring is
performed on paper or smartphone, but long-term superiority over standard of care
self-guided treatment is challenging to maintain.
PMID- 28494137
TI - Acute radiology rarely confirms sinus disease in suspected recurrent acute
rhinosinusitis.
AB - BACKGROUND: Episodic or recurrent sinonasal symptoms are often suspected as
"sinus" in origin. With normal sinus radiology between events, the diagnosis of
recurrent acute rhinosinusitis (RecARS) is made. However, other conditions can
produce episodic symptoms. In this study we analyze acutely performed computed
tomography (CT) in a population with suspected or self-diagnosed "sinus" disease.
METHODS: Patients referred to a tertiary clinic for suspected RecARS were
assessed. Sinus changes were defined by CT (initial assessment) and during the
acute event, by a semiurgent CT performed during the symptomatic episode. Mucosal
thickening, ostiomeatal compromise, and severe septal deformity were recorded.
Symptom profile was assessed during both time-points with the 22-item Sino-Nasal
Outcome Test (SNOT-22). RESULTS: Forty-eight patients (49.5 +/- 14.7 years of
age, 70.8% female) were assessed. At presentation, 75% were resolute in a
diagnosis of "sinus." Baseline Lund-Mackay scores were <6 (median 0
[interquartile range 1]). Ostiomeatal compromise was 6.8% left and 4.5% right at
baseline. Of the patients who returned for acute CT (n = 27), SNOT-22 and
subdomains were similar to baseline. Septal deviation was similar (13.6% vs
15.3%). Acutely, ostiomeatal compromise was 0% left and 7.4% right (n = 2). Of
these 2 patients with ostiomeatal compromise, 1 was diagnosed with RecARS (4%)
and the other with triptan-responsive migraine, with incidental sinus changes.
Final diagnosis was rhinitis (47%), headache/migraine (37%), and facial pain
otherwise undefined (12.5%). CONCLUSION: Patients with a history of "recurrent
acute sinusitis" and normal CT scans between episodes rarely have abnormal CT
findings during acute exacerbations of symptoms. Antibiotics and surgical
intervention are often inappropriate in this population.
PMID- 28494138
TI - Rational Design and Synthesis of 1-(Arylideneamino)-4-aryl-1H-imidazole-2-amine
Derivatives as Antiplatelet Agents.
AB - Based on previous studies indicating the pharmacophoric role of a hydrazone group
and azole rings for antiplatelet aggregation activity, a few series of compounds
with both hydrazone and an azole (imidazole) ring in their structures were
synthesized, and their platelet aggregation inhibitory effects were evaluated.
Two of these 1-(arylideneamino)-4-aryl-1H-imidazole-2-amine derivatives,
compounds 4 a [(E)-1-(benzylideneamino)-4-phenyl-1H-imidazol-2-amine] and 4 p
[(E)-4-phenyl-1-((thiophen-2-ylmethylene)amino)-1H-imidazol-2-amine], exhibited
IC50 values similar to that of acetylsalicylic acid against collagen as a
platelet aggregation inducer. Structural comparison of the synthesized compounds
revealed that those with a para-substituted phenyl ring on the imidazole were
among the most active compounds against platelet aggregation induced by
arachidonic acid (AA), and the presence of a thiophene ring in these compounds
maximized their antiplatelet activity.
PMID- 28494139
TI - Corrigendum to Hsueh (2016), "Neurofeedback training of EEG alpha rhythm enhances
episodic and working memory."
PMID- 28494140
TI - Identification of alpha7 Nicotinic Acetylcholine Receptor Silent Agonists Based
on the Spirocyclic Quinuclidine-Delta2 -Isoxazoline Scaffold: Synthesis and
Electrophysiological Evaluation.
AB - Compound 11 (3-(benzyloxy)-1'-methyl-1'-azonia-4H-1'-azaspiro[isoxazole-5,3'
bicyclo[2.2.2]octane] iodide) was selected from a previous set of nicotinic
ligands as a suitable model compound for the design of new silent agonists of
alpha7 nicotinic acetylcholine receptors (nAChRs). Silent agonists evoke little
or no channel activation but can induce the alpha7 desensitized Ds state, which
is sensitive to a type II positive allosteric modulator, such as PNU-120596.
Introduction of meta substituents into the benzyloxy moiety of 11 led to two sets
of tertiary amines and quaternary ammonium salts based on the spirocyclic
quinuclidinyl-Delta2 -isoxazoline scaffold. Electrophysiological assays performed
on Xenopus laevis oocytes expressing human alpha7 nAChRs highlighted four
compounds that are endowed with a significant silent-agonism profile. Structure
activity relationships of this group of analogues provided evidence of the
crucial role of the positive charge at the quaternary quinuclidine nitrogen atom.
Moreover, the present study indicates that meta substituents, in particular
halogens, on the benzyloxy substructure direct specific interactions that
stabilize a desensitized conformational state of the receptor and induce silent
activity.
PMID- 28494141
TI - Metformin induces osteoblastic differentiation of human induced pluripotent stem
cell-derived mesenchymal stem cells.
AB - Metformin, a first-line antidiabetic drug used by millions of patients, has been
shown to have potential osteogenic properties. The present study was performed to
test the hypothesis that clinically relevant doses of metformin promote the
osteogenic differentiation and mineralization of induced pluripotent stem cell
derived mesenchymal stem cells (iPSC-MSCs). iPSC-MSCs were treated with metformin
(10 MUm) to assess cell viability, osteogenic differentiation, mineralization and
activation of the LKB1/AMP-activated protein kinase (AMPK) signalling pathway, a
surrogate marker of metformin action. To determine its potential application in
MSC-based bone and periodontal tissue engineering, iPSC-MSCs were also treated
with metformin when seeded on to calcium phosphate cement (CPC) scaffolds.
Immunoblotting and cellular uptake assays showed that iPSC-MSCs express
functional organic cation transporter-1 (OCT-1), a transmembrane protein that
mediates the intracellular uptake of metformin. Although metformin treatment did
not impair iPSC-MSC viability, it significantly stimulated alkaline phosphatase
activity, enhanced mineralized nodule formation and increased expression of
osteogenic markers, including Runt-related transcription factor 2 (RUNX2) and
osterix. Inhibition of LKB1 activity, a common upstream AMPK kinase, markedly
reversed metformin-induced AMPK activation, RUNX2 expression and nuclear
localization. Moreover, metformin substantially increased mineralized nodule
formation of iPSC-MSC seeded on CPC scaffolds. Collectively, functional OCT
expressing iPSC-MSCs responded to metformin by inducing an osteogenic effect in
part mediated by the LKB1/AMPK pathway. Considering the widespread use of
metformin in diabetics, this work may lead to novel tissue-engineering platforms
where autogenous OCT-expressing iPSC-MSCs might be used to enhance bone and
periodontal regeneration in diabetic patients prescribed with daily doses of
metformin.
PMID- 28494142
TI - Blood pressure circadian rhythms and adverse outcomes in type 2 diabetes patients
diagnosed with orthostatic hypotension.
AB - AIMS/INTRODUCTION: Patients with diabetes frequently develop orthostatic
hypotension (OH). The present study was designed to examine the relationship of
blood pressure (BP) circadian rhythms and outcomes in diabetes with OH. MATERIALS
AND METHODS: In the present study, 173 inpatients with type 2 diabetes were
enrolled. Patients were divided into an OH group and a non-OH group according to
the BP changes detected in the supine and standing position. Then, 24-h
ambulatory BP was monitored. Patients were followed up for an average of 45 +/-
10 months post-discharge. Outcomes - death and major adverse cardiac and
cerebrovascular events, including heart failure, myocardial infarction and stroke
- were recorded. RESULTS: There were 61 patients (35.26%) in the OH group and 112
patients (64.74%) in the non-OH group. In the OH group, the night-time systolic
BP and night-time diastolic BP were higher, the blood BP rhythms were
predominantly of the riser type (67.21%). OH was as an independent marker of
riser type circadian rhythm (adjusted odds ratio 4.532, 95% confidence interval
2.579-7.966). In the OH group, the incidence rates of mortality, and major
adverse cardiac and cerebrovascular events were increased significantly compared
with those in the non-OH group (11.48 vs 2.68%, P = 0.014; 37.70 vs 8.93%, P <
0.01). CONCLUSIONS: In patients who had type 2 diabetes diagnosed with OH, the BP
circadian rhythm usually showed riser patterns, and they had increased rates of
mortality, and major adverse cardiac and cerebrovascular events.
PMID- 28494144
TI - Thermo-optical Characterization of Photothermal Optical Phase Shift Detection in
Extended-Nano Channels and UV Detection of Biomolecules.
AB - The expansion of microfluidics research to nanofluidics requires absolutely
sensitive and universal detection methods. Photothermal detection, which utilizes
optical absorption and nonradiative relaxation, is promising for the sensitive
detection of nonlabeled biomolecules in nanofluidic channels. We have previously
developed a photothermal optical phase shift (POPS) detection method to detect
nonfluorescent molecules sensitively, while a rapid decrease of the sensitivity
in nanochannels and the introduction of an ultraviolet (UV) excitation system
were issues to be addressed. In the present study, our primary aim is to
characterize the POPS signal in terms of the thermo-optical properties and
quantitatively evaluate the causes for the decrease in sensitivity. The UV
excitation system is then introduced into the POPS detector to realize the
sensitive detection of nonlabeled biomolecules. The UV-POPS detection system is
designed and constructed from scratch based on a symmetric microscope. The
results of simulations and experiments reveal that the sensitivity decreases due
to a reduction of the detection volume, dissipation of the heat, and cancellation
of the changes in the refractive indices. Finally, determination of the
concentration of a nonlabeled protein (bovine serum albumin) is performed in a
very thin 900 nm deep nanochannel. As a result, the limit of detection (LOD) is
2.3 MUM (600 molecules in the 440 attoliter detection volume), which is as low as
that previously obtained for our visible POPS detector. UV-POPS detection is thus
expected be a powerful technique for the study of biomolecules, including DNAs
and proteins confined in nanofluidic channels.
PMID- 28494143
TI - Normal meal tolerance test is preferable to the glucagon stimulation test in
patients with type 2 diabetes that are not in a hyperglycemic state: Comparison
with the change of C-peptide immunoreactivity.
AB - AIMS/INTRODUCTION: The aim of the present study was to evaluate the properties of
the glucagon stimulation test (GST) and the normal meal tolerance test (NMTT) in
patients with type 2 diabetes. MATERIALS AND METHODS: We enrolled 142 patients
with type 2 diabetes, and carried out a GST and a NMTT. We carried out the NMTT
using a calorie-controlled meal based on an intake of 30 kcal/kg ideal
bodyweight/day. We calculated the change in C-peptide immunoreactivity (DeltaCPR)
by subtracting fasting CPR from the CPR 6 min after the 1-mg glucagon injection
(GST) or 120 min after the meal (NMTT). RESULTS: Mean DeltaCPR for the GST was
2.0 ng/mL, and for the NMTT was 3.1 ng/mL. A total of 104 patients had greater
DeltaCPR in the NMTT than the GST, and the mean DeltaCPR was significantly
greater in the NMTT than the GST (P < 0.05). To exclude any influence of
antidiabetic drugs, we examined 42 individuals not taking antidiabetic agents,
and found the mean DeltaCPR was significantly greater in the NMTT than the GST
(GST 2.4 ng/mL, NMTT 4.3 ng/mL; P < 0.05). To consider the influence of glucose
toxicity, we carried out receiver operating characteristic analyses with fasting
plasma glucose and glycated hemoglobin. The optimal cut-off levels predicting GST
DeltaCPR to be larger than NMTT DeltaCPR were fasting plasma glucose 147 mg/dL
and glycated hemoglobin 9.0% (fasting plasma glucose: sensitivity 0.64,
specificity 0.76, area under the curve 0.73; glycated hemoglobin: sensitivity
0.56, specificity 0.71, area under the curve 0.66). CONCLUSIONS: The NMTT is a
reliable insulin secretion test in patients with type 2 diabetes, except for
those in a hyperglycemic state.
PMID- 28494145
TI - Direct Plasmon-Accelerated Electrochemical Reaction on Gold Nanoparticles.
AB - Direct photocatalysis making use of plasmonic metals has attracted significant
attention due to the light-harnessing capabilities of these materials associated
with localized surface plasmon resonance (LSPR) features. Thus far, most reported
work has been limited to plasmon-induced chemical transformations. Herein, we
demonstrate that electrochemical reactions can also be accelerated by plasmonic
nanoparticles upon LSPR excitation. Using glucose electrocatalysis as a model
reaction system, the direct plasmon-accelerated electrochemical reaction (PAER)
on gold nanoparticles is observed. The wavelength- and solution-pH-dependent
electrochemical oxidation rate and the dark-field scattering spectroscopy results
confirm that the hot charge carriers generated during plasmon decay are
responsible for the enhanced electrocatalysis performance. Based on the proposed
PAER mechanism, a plasmon-improved glucose electrochemical sensor is constructed,
demonstrating the enhanced performance of the non-enzyme sensor upon LSPR
excitation. This plasmon-accelerated electrochemistry promises potential
applications in (bio)electrochemical energy conversion, electroanalysis, and
electrochemical devices.
PMID- 28494146
TI - Redox-Induced Gating of the Exchange Interactions in a Single Organic Diradical.
AB - Embedding a magnetic electroactive molecule in a three-terminal junction allows
for the fast and local electric field control of magnetic properties desirable in
spintronic devices and quantum gates. Here, we provide an example of this control
through the reversible and stable charging of a single all-organic neutral
diradical molecule. By means of inelastic electron tunnel spectroscopy we show
that the added electron occupies a molecular orbital distinct from those
containing the two radical electrons, forming a spin system with three
antiferromagnetically coupled spins. Changing the redox state of the molecule
therefore switches on and off a parallel exchange path between the two radical
spins through the added electron. This electrically controlled gating of the
intramolecular magnetic interactions constitutes an essential ingredient of a
single-molecule [Formula: see text] quantum gate.
PMID- 28494147
TI - Structural Insight into the Stabilizing Effect of O-Glycosylation.
AB - Protein glycosylation has been shown to have a variety of site-specific and
glycan-specific effects, but so far, the molecular logic that leads to such
observations has been elusive. Understanding the structural changes that occur
and being able to correlate those with the physical properties of the
glycopeptide are valuable steps toward being able to predict how specific
glycosylation patterns will affect the stability of glycoproteins. By
systematically comparing the structural features of the O-glycosylated
carbohydrate-binding module of a Trichoderma reesei-derived Family 7
cellobiohydrolase, we were able to develop a better understanding of the
influence of O-glycan structure on the molecule's physical stability. Our results
indicate that the previously observed stabilizing effects of O-glycans come from
the introduction of new bonding interactions to the structure and increased
rigidity, while the decreased stability seemed to result from the impaired
interactions and increased conformational flexibility. This type of knowledge
provides a powerful and potentially general mechanism for improving the stability
of proteins through glycoengineering.
PMID- 28494148
TI - Raman Spectroscopy of Lattice-Matched Graphene on Strongly Interacting Metal
Surfaces.
AB - Regardless of the widely accepted opinion that there is no Raman signal from
single-layer graphene when it is strongly bonded to a metal surface, we present
Raman spectra of a graphene monolayer on Ni(111) and Co(0001) substrates. The
high binding energy of carbon to these surfaces allows formation of lattice
matched (1 * 1) structures where graphene is significantly stretched. This is
reflected in a record-breaking shift of the Raman G band by more than 100 cm-1
relative to the case of freestanding graphene. Using electron diffraction and
photoemission spectroscopy, we explore the aforementioned systems together with
polycrystalline graphene on Co and analyze possible intercalation of oxygen at
ambient conditions. The results obtained are fully supported by Raman
spectroscopy. Performing a theoretical investigation of the phonon dispersions of
freestanding graphene and stretched graphene on the strongly interacting Co
surface, we explain the main features of the Raman spectra. Our results create a
reliable platform for application of Raman spectroscopy in diagnostics of
chemisorbed graphene and related materials.
PMID- 28494149
TI - Comparison of Three Antihapten VHH Selection Strategies for the Development of
Highly Sensitive Immunoassays for Microcystins.
AB - Owing to their reproducibility, stability, and cost-effective production, the
recombinant variable domains of heavy-chain-only antibodies (VHHs) are becoming a
salient option as immunoassay reagents. Recently, there have been several reports
describing their application to the detection of small molecules (haptens).
However, lacking the heavy-light chain interface of conventional antibodies, VHHs
are not particularly apt to bind small analytes and failures are not uncommon.
Here we describe the construction of a VHH phage display library against the
cyanobacterial hepatotoxin microcystin LR and its selection using competitive
panning and two novel panning strategies. The outcome of each strategy was
evaluated by a large-scale screening using in vivo biotinylated nanobodies. The
three methods selected for different nonoverlapping subsets of VHHs, allowing one
to optimize the immunodetection of the toxin. The best results were obtained by
promoting the isolation of VHHs with the slowest koff (off-rate selection). Among
these, the biotinylated nanobody A2.3 performed in ELISA with excellent recovery
and high sensitivity, IC50 = 0.28 MUg/L, with a limit of detection that is well
below the most rigorous guidelines for the toxin. While it may be case-specific,
these results highlight the importance of exploring different panning strategies
to optimize the selection of antihapten nanobodies.
PMID- 28494150
TI - Nondestructive Redox Quantification Reveals Glassmaking of Rare French Gothic
Stained Glasses.
AB - The sophisticated colors of medieval glasses arise from their transition metal
(TM) impurities and capture information about ancient glassmaking techniques.
Beyond the glass chemical composition, the TM redox is also a key factor in the
glass color, but its quantification without any sampling is a challenge. We
report a combination of nondestructive and noninvasive quantitative analyses of
the chemical composition by particle-induced X-ray emission-particle-induced
gamma-ray emission mappings and of the color and TM element speciation by optical
absorption spectroscopy performed on a red-blue-purple striped glass from the
stained glass windows of the Sainte-Chapelle in Paris, France, during its
restoration. These particular glass pieces must have been produced as a single
shot, which guarantees that the chemical variations reflect the recipe in use in
a specific medieval workshop. The quantitative elemental mappings demonstrate
that the colored glass parts are derived from the same base glass, to which TMs
were deliberately added. Optical absorption spectra reveal the origin of the
colors: blue from CoII, red from copper nanoparticles, and purple from MnIII.
Furthermore, the derivation of the quantitative redox state of each TM in each
color shows that the contents of Fe, Cu, and Mn were adjusted to ensure a
reducing glass matrix in the red stripe or a metastable overoxidized glass in the
purple stripe. We infer that the agility of the medieval glassmaker allowed him
to master the redox kinetics in the glass by rapid shaping and cooling to obtain
a snapshot of the thermodynamically unstable glass colors.
PMID- 28494151
TI - Design of HIV Coreceptor Derived Peptides That Inhibit Viral Entry at
Submicromolar Concentrations.
AB - HIV/AIDS continues to pose an enormous burden on global health. Current HIV
therapeutics include inhibitors that target the enzymes HIV protease, reverse
transcriptase, and integrase, along with viral entry inhibitors that block the
initial steps of HIV infection by preventing membrane fusion or virus-coreceptor
interactions. With regard to the latter, peptides derived from the HIV coreceptor
CCR5 were previously shown to modestly inhibit entry of CCR5-tropic HIV strains,
with a peptide containing residues 178-191 of the second extracellular loop
(peptide 2C) showing the strongest inhibition. Here we use an iterative approach
of amino acid scanning at positions shown to be important for binding the HIV
envelope, and recombining favorable substitutions to greatly improve the potency
of 2C. The most potent candidate peptides gain neutralization breadth and inhibit
CXCR4 and CXCR4/CCR5-using viruses, rather than CCR5-tropic strains only. We
found that gains in potency in the absence of toxicity were highly dependent on
amino acid position and residue type. Using virion capture assays we show that 2C
and the new peptides inhibit capture of CD4-bound HIV-1 particles by antibodies
whose epitopes are located in or around variable loop 3 (V3) on gp120. Analysis
of antibody binding data indicates that interactions between CCR5 ECL2-derived
peptides and gp120 are localized around the base and stem of V3 more than the
tip. In the absence of a high-resolution structure of gp120 bound to coreceptor
CCR5, these findings may facilitate structural studies of CCR5 surrogates, design
of peptidomimetics with increased potency, or use as functional probes for
further study of HIV-1 gp120-coreceptor interactions.
PMID- 28494152
TI - Low-Temperature Synthesis of Carbon-Rich Nanoparticles with a Clickable Surface
for Functionalization.
AB - Carbon nanoparticles (CNPs) are promising materials for optoelectronic and
biomedical applications thanks to their optical properties, low production cost,
and superior biocompatibility compared to traditional semiconductor quantum dots.
The countless synthetic methods reported allow a library of diverse CNP
structures and optical properties, guiding their subsequent applications.
However, the current drawbacks lie mainly within these synthetic processes, as
many of them require harsh conditions preventing control over morphology and
often generating chemically inert nanoparticles. Thus, more advances on low
temperature and controllable synthetic processes are desirable. In this study, we
suggest a new strategy to synthesize CNPs with tunable size, while avoiding the
use of harsh conditions and allowing easy surface functionalization. The
metastable state of polyyne-containing materials appoints them as ideal
precursors for low-temperature preparation of carbon-rich structures. Our
approach is to synthesize octatetrayne-containing particles prompt to spontaneous
reaction, including topochemical polymerization, followed by aromatization, to
avoid harsh carbonization steps. For the particle synthesis, the well-known
dispersion polymerization process has been adapted for homocoupling of terminal
butadiynes, generating the octatetrayne-containing particles. The method was
proven reproducible, scalable, and versatile, as the particles' size can be
modulated between 50 and 170 nm. Surface functionalization via thiol-yne click
chemistry was completed with a pyrene-modified thiol ligand to provide the CNPs
with photoactive properties in the visible range. The functionalized particles
exhibit fluorescence at 470 nm arising from excimer formation.
PMID- 28494153
TI - Polyaniline and Perfluorosulfonic Acid Co-Stabilized Metal Catalysts for Oxygen
Reduction Reaction.
AB - A proton (perfluorosulfonic acid, PFSA) and electron (polyaniline, PANI)
conductor polymer costabilized Pt catalyst (Pt-PFSA/C@PANI) is synthesized to
improve the long-term stability of polymer electrolyte membrane fuel cells
(PEMFCs). The prepared catalyst not only displays comparable oxygen reduction
reaction (ORR) activity, but significantly higher electrochemical stability than
commercial porous carbon nanosphere supported Pt catalysts (Pt/C). This robust
electrochemical property can be due to the result of PFSA and PANI. PANI as
protector inhibits carbon nanospheres from corrosion of carbon supports in harsh
chemical and electrochemical conditions. Meanwhile, PFSA wrapped Pt NPs (Pt@PFSA)
can also anchor Pt NPs on C@PANI to avoid aggregation and detachment of Pt NPs,
due to the increased metal-support interaction caused by the strong electrostatic
attraction between PANI and PFSA with corresponding positive and negative
charges. Significantly, after coating PANI on carbon supports (C@PANI), almost
all micropores in the surface of carbon disappear, effectively avoiding the
embedding of Pt nanopaticles into micropores. Furthermore, the triple-phase
boundary toward ORR catalysis can be facilitated by PFSA as proton conductor
(solid electrolyte). These are of benefit to increase utilization of Pt noble
metals and ORR activity of our new catalysts.
PMID- 28494154
TI - Adsorption of Estrogen Contaminants by Graphene Nanomaterials under Natural
Organic Matter Preloading: Comparison to Carbon Nanotube, Biochar, and Activated
Carbon.
AB - Adsorption of two estrogen contaminants (17beta-estradiol and 17alpha-ethynyl
estradiol) by graphene nanomaterials was investigated and compared to those of a
multi-walled carbon nanotube (MWCNT), a single-walled carbon nanotube (SWCNT),
two biochars, a powdered activated carbon (PAC), and a granular activate carbon
(GAC) in ultrapure water and in the competition of natural organic matter (NOM).
Graphene nanomaterials showed comparable or better adsorption ability than carbon
nanotubes (CNTs), biochars (BCs), and activated carbon (ACs) under NOM
preloading. The competition of NOM decreased the estrogen adsorption by all
adsorbents. However, the impact of NOM on the estrogen adsorption was smaller on
graphenes than CNTs, BCs, and ACs. Moreover, the hydrophobicity of estrogens also
affected the uptake of estrogens. These results suggested that graphene
nanomaterials could be used to removal estrogen contaminants from water as an
alternative adsorbent. Nevertheless, if transferred to the environment, they
would also adsorb estrogen contaminants, leading to great environmental hazards.
PMID- 28494155
TI - Principles for Tuning Hydrophobic Ligand-Receptor Binding Kinetics.
AB - We investigate how to tune the rate of hydrophobic ligand-receptor association
due to the role of solvent in adjustable receptor pockets by explicit-water
molecular dynamics (MD) simulations. Our model considers the binding of a
spherical ligand (key/guest) to a concave surface recess in a nonpolar wall as
receptor (lock/host). We systematically modify the receptor's physicochemical
properties in terms of geometry and dispersion attraction which, in turn, alter
the water occupancy and fluctuations within the pocket. We demonstrate that even
minor pocket modifications can lead to a significant acceleration of the water
mediated association. For example, the binding switches from comparably slow to
fast if the binding pocket becomes only slightly deeper. We find that the degree
of hydrophobicity, characterized by hydration occupancy and its fluctuations,
clearly correlates with the binding times and, for instance, links the sudden
acceleration to an abrupt increase in hydrophobicity. For a deeper analysis based
on passage time theory, we quantify the intimate coupling between solvent
fluctuations and the ligand's local dynamics and friction. The coupling exhibits
substantial nonequilibrium effects and maximizes shortly before binding, which
slows down the binding kinetics in all cases. In summary, we rationalize how the
physicochemical properties of a nonpolar, concave binding site tune key-lock
binding kinetics due to water-mediated forces and fluctuations. Our study thus
complements the profound understanding of the solvent's influence in host-guest
binding, which is essential for tailored solutions in catalysis and
pharmaceutical applications.
PMID- 28494156
TI - Spatial Control of Condensation on Chemically Homogeneous Pillar-Built Surfaces.
AB - The random nature of dropwise condensation impedes spatial control hereof and its
use for creating microdroplet arrays, yet here we demonstrate the spatial control
of dropwise condensation on a chemically homogeneous pillar array surface,
yielding ~8000 droplets/mm2 under normal atmospheric pressure conditions. The
studied pillar array surface is defined by photolithography and etched in silicon
by deep reactive ion etching. Subsequently, the surface is covered with a self
assembled monolayer of perfluorodecyltrichlorosilane (FDTS) to render the surface
hydrophobic. To obtain a perfect droplet array, with one droplet per pillar, we
exploit a phenomenon where the water vapor flux is focused on the apexes of
surface asperities by diffusion while matching the nucleation point density to
the array dimensions. Matching is here achieved through the variation of
interpillar distance and vapor flow conditions.
PMID- 28494157
TI - Side Fenestrations Provide an "Anchor" for a Stable Binding of A1899 to the Pore
of TASK-1 Potassium Channels.
AB - A1899 is a potent and selective inhibitor of the two-pore domain potassium (K2P)
channel TASK-1. It was previously reported that A1899 acts as an open-channel
blocker and binds to residues of the P1 and P2 regions, the M2 and M4 segments,
and the halothane response element. The recently described crystal structures of
K2P channels together with the newly identified side fenestrations indicate that
residues relevant for TASK-1 inhibition are not purely facing the central cavity
as initially proposed. Accordingly, the TASK-1 binding site and the mechanism of
inhibition might need a re-evaluation. We have used TASK-1 homology models based
on recently crystallized K2P channels and molecular dynamics simulation to
demonstrate that the highly potent TASK-1 blocker A1899 requires binding to
residues located in the side fenestrations. Unexpectedly, most of the previously
described residues that interfere with TASK-1 blockade by A1899 project their
side chains toward the fenestration lumina, underlining the relevance of these
structures for drug binding in K2P channels. Despite its hydrophobicity, A1899
does not seem to use the fenestrations to gain access to the central cavity from
the lipid bilayer. In contrast, binding of A1899 to residues of the side
fenestrations might provide a physical "anchor", reflecting an energetically
favorable binding mode that after pore occlusion stabilizes the closed state of
the channels.
PMID- 28494158
TI - "Electron/Ion Sponge"-Like V-Based Polyoxometalate: Toward High-Performance
Cathode for Rechargeable Sodium Ion Batteries.
AB - One key challenge facing room temperature Na-ion batteries lies in identifying
earth-abundant, environmentally friendly and safe materials that can provide
efficient Na+ storage sites in Na-ion batteries. Herein, we report such a
material, polyoxometalate Na2H8[MnV13O38] (NMV), with entirely different
composition and structure from those cathode compounds reported before. Ex-situ
XPS and FTIR analyses reveal that NMV cathode behaves like an "electron/Na-ion
sponge", with 11 electrons/Na+ acceptability per mole, which has a decisive
contribution to the high capacity. The extraordinary structural features,
evidenced by X-ray crystallographic analysis, of Na2H8[MnV13O38] with a flexible
2D lamellar network and 1D open channels provide diverse Na ion migration
pathways, yielding good rate capability. First-principle calculations demonstrate
that a super-reduced state, [MnV13O38]20-, is formed with slightly expanded size
(ca. 7.5%) upon Na+ insertion compared to the original [MnV13O38]9-. This "ion
sponge" feature ensures the good cycling stability. Consequently, benefiting from
the combinations of "electron/ion sponge" with diverse Na+ diffusion channels,
when revealed as the cathode materials for Na-ion batteries, Na2H8[MnV13O38]/G
exhibits a high specific capacity (ca. 190 mA h/g at 0.1 C), associates with a
good rate capability (130 mA h/g at 1 C), and a good capacity retention (81% at
0.2 C). Our results promote better understanding of the storage mechanism in
polyoxometalate host, enrich the existing rechargeable SIBs cathode chemistry,
and enlighten an exciting direction for exploring promising cathode materials for
Na-ion batteries.
PMID- 28494159
TI - Association of Visual Acuity with Ocular Dominance in 2045 Myopic Patients.
AB - PURPOSE: Previous studies of the relationship between visual acuity (VA) and
ocular dominance have produced conflicting results. We hypothesized that (1) the
discrepancies were related mostly to sample size and interocular visual acuity
difference (IOVAD); (2) in large samples of individuals with marked IOVADs, the
eye with the better uncorrected distance visual acuity (UDVA) would be dominant.
These hypotheses were tested in a large group of myopic patients. METHODS: This
prospective study of cycloplegic refraction involved 2045 myopic refractive
surgery candidates. Patients with amblyopia or strabismus were excluded. Ocular
dominance was assessed using the hole-in-the-card test. RESULTS: In 2045
patients, the dominant eye had significantly better UDVA (p = 0.028) and was less
astigmatic (p = 0.000) than the nondominant eye. In 426 patients with marked
interocular difference in the UDVA (>=0.2 logMAR), the dominant eye not only had
significant UDVA (p = 0.022) but also significantly less myopic (p = 0.028) and
had a shorter axial length (AL; p = 0.001). In patients with smaller differences
in UDVA (0.1 logMAR, n = 411) or no difference (n = 1208), the dominant and
nondominant eyes did not differ significantly with respect to UDVA, myopic power,
and AL (p > 0.05). CONCLUSIONS: The present study showed that the dominant eyes
had significantly better UDVA than the nondominant eyes, especially in
individuals with marked differences in UDVA. These results supported our
hypothesis regarding the relationship between better VA and ocular dominance.
PMID- 28494160
TI - Forensic Psychological Assessment in Forensic Practice: Case Studies.
PMID- 28494161
TI - The Anxiety Depression Distress Inventory-27 (ADDI-27): New Evidence of Factor
Structure, Item-Level Measurement Invariance, and Validity.
AB - Three studies examining the factor structure and psychometric properties of the
Anxiety Depression Distress Inventory-27 (ADDI-27) extended the initial
instrument development studies for this recently introduced inventory. The ADDI
27 is an empirically derived short form of the Mood and Anxiety Questionaire-90
(MASQ-90) comprising three scales: Positive Affect, Somatic Anxiety, and General
Distress. The main objectives of Study 1 (N = 700) were to examine the factor
structure of the ADDI-27 and its measurement invariance across gender at the item
level. The objective of Study 2 (N = 538) was to examine evidence for the
convergent and discriminant validity of scores on the ADDI-27. The objective of
Study 3 (N = 240) was to assess further evidence for the nomological network and
convergent and discriminant validity of the ADDI-27 scores. Results of
exploratory structural equation modeling yielded strong support for a 3-factor
model, with approximate fit indexes meeting or exceeding the conventional
cutoffs. With p <= .001 as the criterion for detecting noninvariance, results of
measurement invariance analysis suggested that all of the ADDI-27 items were
invariant across gender. Results of multivariate validity analyses across 2
studies provided support for the convergent and discriminant validity of scores
on the ADDI-27 scales.
PMID- 28494162
TI - Are automatic systems the future of motorcycle safety? A novel methodology to
prioritize potential safety solutions based on their projected effectiveness.
AB - OBJECTIVE: Motorcycle riders are involved in significantly more crashes per
kilometer driven than passenger car drivers. Nonetheless, the development and
implementation of motorcycle safety systems lags far behind that of passenger
cars. This research addresses the identification of the most effective motorcycle
safety solutions in the context of different countries. METHODS: A knowledge
based system of motorcycle safety (KBMS) was developed to assess the potential
for various safety solutions to mitigate or avoid motorcycle crashes. First, a
set of 26 common crash scenarios was identified from the analysis of multiple
crash databases. Second, the relative effectiveness of 10 safety solutions was
assessed for the 26 crash scenarios by a panel of experts. Third, relevant
information about crashes was used to weigh the importance of each crash scenario
in the region studied. The KBMS method was applied with an Italian database, with
a total of more than 1 million motorcycle crashes in the period 2000-2012.
RESULTS: When applied to the Italian context, the KBMS suggested that automatic
systems designed to compensate for riders' or drivers' errors of commission or
omission are the potentially most effective safety solution. The KBMS method
showed an effective way to compare the potential of various safety solutions,
through a scored list with the expected effectiveness of each safety solution for
the region to which the crash data belong. A comparison of our results with a
previous study that attempted a systematic prioritization of safety systems for
motorcycles (PISa project) showed an encouraging agreement. CONCLUSIONS: Current
results revealed that automatic systems have the greatest potential to improve
motorcycle safety. Accumulating and encoding expertise in crash analysis from a
range of disciplines into a scalable and reusable analytical tool, as proposed
with the use of KBMS, has the potential to guide research and development of
effective safety systems. As the expert assessment of the crash scenarios is
decoupled from the regional crash database, the expert assessment may be
reutilized, thereby allowing rapid reanalysis when new crash data become
available. In addition, the KBMS methodology has potential application to injury
forecasting, driver/rider training strategies, and redesign of existing road
infrastructure.
PMID- 28494163
TI - Expression of 14-3-3 Zeta Protein in Dexamethasone-Treated Mice and Human TM-1
Cells.
AB - PURPOSE: 14-3-3 zeta protein plays a potential protective role in
neurodegenerative disease. Given that glaucoma and neurodegenerative diseases
share a similar pathogenesis, it is possible that 14-3-3 zeta may have a similar
protective effect in the glaucomatous process. In the present study, we measured
the expression of 14-3-3 zeta in vivo (mouse eyes) and in vitro in a transformed
human trabecular meshwork (HTM) cell line, TM-1, and assessed the possible roles
of this protein in dexamethasone (DEX)-treated eyes and HTM cells. METHODS: Mouse
eyes were randomly treated with 0.1% dexamethasone (DEX) eye drops or phosphate
buffered solution (PBS) for 28 days. The expression and distribution of 14-3-3
zeta protein in mouse eyes were examined using immunofluorescence. TM-1 cells
were treated with DEX (10-6 or 10-7 M) or PBS for 1, 4, or 7 days, and the mRNA
and protein expression of 14-3-3 zeta were detected by real-time RT-PCR and
Western blotting. RESULTS: 14-3-3 zeta protein was highly expressed in the mouse
cornea, trabecular meshwork (TM), and ciliary body. Intraocular pressure (IOP)
was significantly elevated, whereas the 14-3-3 zeta expression was significantly
decreased in mouse TM after 0.1% DEX treatment for 28 days. In vitro, treatment
with 10-7 M DEX mildly increased 14-3-3 zeta mRNA and protein expression (p >
0.05), whereas 10-6 M DEX significantly decreased expression of 14-3-3 zeta mRNA
and protein (p < 0.05) compared to the control (Ctrl) group at the seventh day.
CONCLUSIONS: DEX can increase IOP in mouse eyes and concurrently downregulate 14
3-3 zeta protein expression in mouse TM. The effects of DEX on 14-3-3 zeta
expression in vitro were both dose- and time-related. Our results suggest that
alterations in 14-3-3 zeta protein may be implicated in DEX-induced pathological
elevated IOP.
PMID- 28494164
TI - Effects of enhancing vitamin D status by 25-hydroxycholecalciferol
supplementation, alone or in combination with calcium and phosphorus, on sternum
mineralisation and breast meat quality in broilers.
AB - 1. The aim of the present study was to examine the effects of improving vitamin D
status in broiler diets by supplementary 25-hydroxycholecalciferol (25OHD3),
alone or in combination with calcium (Ca) and available phosphorus (aP), on live
performance, sternum mineralisation and breast meat quality in broilers. 2. A
total of 936 1-d-old Ross 308 broilers were used in the study. After gender
determination at the hatchery, chicks from each sex were randomly distributed
into three dietary treatments. The following dietary treatments were used in the
experiment from hatch to 38 d: (1) A control diet formulated to meet all of the
nutrient requirements of broiler chicks according to the management guide; (2)
The control diet supplemented with 18.7-15.0 ug/kg of 25OHD3; and (3) The control
diet supplemented with 18.7-15.0 ug/kg of 25OHD3 plus Ca + aP. 3. Improvement in
vitamin D status by 25OHD3 supplementation, alone or in combination with Ca and
aP, had no effect on body weight and feed conversion ratio of broilers. 4. The
serum 25OHD3 concentration significantly increased with 25OHD3 and 25OHD3 plus Ca
+ aP supplementation (P < 0.05), whereas the ionised Ca and Mg concentrations
remained unchanged. 5. Sternum absolute weight, ash content and the
concentrations of Ca and P significantly increased (P < 0.01) with
supplementation of 25OHD3, alone or in combination with Ca + aP. 6. Supplemental
25OHD3, alone or in combination with Ca + aP, slightly increased pH24 (P = 0.05)
and decreased (P < 0.01) squeezable water loss in breast meat, whereas it had no
significant effect on lightness, yellowness and sarcoplasmic protein solubility.
7. In conclusion, the results suggested that enhancing vitamin D status by 25OHD3
supplementation alone or in combination with Ca + aP may improve sternum
structure and mineral accretion. Furthermore, supplemental 25OHD3, even in a
nutritionally complete diet, may offer an effective way to improve protein
solubility in female broilers.
PMID- 28494165
TI - Effect of feed supplementation with Satureja khuzistanica essential oil on
performance and physiological parameters of broilers fed on wheat- or maize-based
diets.
AB - 1. The aim of this study was to evaluate various levels of Satureja khuzistanica
essential oil (SKEO) on performance and physiological parameters of broilers fed
on wheat- or maize-based diets. 2. Treatments consisted of two cereals (maize- or
wheat-based diets) and three levels of SKEO)0, 250 and 500 mg/kg). 3. Feed intake
(FI) and body weight gain (BWG) decreased in broilers fed on the wheat-based
diets compared to the control diet. Dietary supplementation of 500 mg/kg SKEO
increased FI and BWG. Dietary SKEO supplementation was effective in improving FI
and BWG only in wheat-based diets and was effective in improving feed conversion
ratio (FCR) in both diets. 4. Dietary supplementation of 500 mg/kg SKEO caused a
significant decrease in plasma cholesterol and triglycerides. Also, plasma low
density lipoprotein concentration was decreased in broilers fed on 250 and 500
mg/kg of SKEO. Plasma cholesterol levels in birds fed on the wheat-based diets
were lower than in those fed on maize-based diets. 5. Dietary supplementation of
500 mg/kg SKEO increased caecal population of Lactobacillus and reduced total
bacterial and Escherichia coli count. Caecal population of Lactobacillus
decreased in broilers fed on the wheat-based diets. 6. Digesta viscosity was
increased in broilers fed on the wheat-based diets and decreased in broilers fed
on 500 mg/kg SKEO compared to the control diet. Dietary SKEO supplementation was
effective in reducing digesta viscosity values only in wheat-based diets. 7.
Villus height of the duodenum and jejunum decreased in broilers fed on the wheat
based diets. Dietary supplementation of 500 mg/kg SKEO increased villus height
and villus height-to-crypt depth ratios and decreased crypt depth of the duodenum
compared to the control diet. 8. It can be concluded that dietary SKEO
supplementation was effective in improving FI, BWG and FCR values in wheat-based
diets.
PMID- 28494166
TI - Ocular Safety of Intravitreal Connective Tissue Growth Factor Neutralizing
Antibody.
AB - PURPOSE: To detect the safety of intravitreal injection of anti-connective tissue
growth factor (CTGF) (IVAC) in rat eyes in order to apply this neutralizing
antibody for experimental animal studies. METHODS: Forty-five Lister Hooded male
pigmented rats were divided into five groups that received IVAC (2 MUl)
corresponding to the doses of 10 (B), 20 (C), 50 (D), and 100 MUg/ml (E), equal
to 1.25, 2.5, 6.25, and 12.5 ug/ml of antibody concentration in rat vitreous,
respectively. The sham group (A) received 2 MUl of normal saline. Full field
electroretinography (ERG) was performed at baseline and on days 7 and 28 after
IVAC. The animals were euthanized and the corresponding eyes were subjected to
routine histopathology, immunohistochemistry for glial fibrillary acidic protein
(GFAP), and terminal transferase dUTP nick end-labeling (TUNEL) assay. RESULTS:
Scotopic rod b-wave amplitude and maximal combined b-wave amplitude were 111.89
+/- 71.2 and 178.57 +/- 55.58 MUV, respectively, at baseline which significantly
reduced to 79.31 +/- 52.59 and 128.73 +/- 41.61 MUV, respectively, after 28 days
in group E (p < 0.05). There was no significant reduction of amplitudes in other
groups with lower doses of anti-CTGF antibody. Retinal ganglion cells were
significantly decreased in group E as compared to other groups. GFAP immune
reactivity was not significant in any of the groups. TUNEL test showed inner
retinal neural cell apoptosis only in group E. CONCLUSIONS: ERG, histopathologic,
and apoptotic assays revealed no toxic effects of 10-50 MUg/ml of IVAC in rat
eyes. Using 100 MUg/ml IVAC led to a significant toxic effect in terms of
functional, histopathologic, and TUNEL findings.
PMID- 28494167
TI - "My Whole Life is Ethics!" Ordinary Ethics and Gene Therapy Clinical Trials.
AB - What and where is ethics in gene therapy? Historical debates have identified a
set of ethical issues with the field, and current regulatory systems presume a
discrete ethics that can be achieved or protected. Resisting attempts at
demarcation or resolution, we use the notions of "ordinary" or "everyday" ethics
to develop a better understanding of the complexities of experimental gene
therapy for patients, families, and practitioners and create richer imaginings of
ethics in the gene therapy sphere. Drawing on ethnographic research in several
clinical trials, we show that patients/parents can acquire some control in
difficult medical situations, and practitioners can attune their care to their
patients' needs. The human provenance of gene therapy practice, and the
irreducible sociality of ethics, means that understanding the ethics of this
medical field also requires understanding the everyday worlds and relationships
of those at its heart.
PMID- 28494168
TI - Uveal Melanoma Risk Factors: A Systematic Review of Meta-Analyses.
AB - PURPOSE: There is currently no clinical risk-assessment tool allowing
identification of patients at risk for developing uveal melanoma (UM) who might
benefit from regular screening. As a first step toward the elaboration of such a
tool, we systematically reviewed UM risk factors already established by meta
analysis. METHODS: Two reviewers independently screened Pubmed, Medline, Embase,
and Web of Science from their respective inception dates until July 2016 using a
combination of keywords and MeSH terms. Eligible studies were meta-analyses or
systematic reviews providing pooled odds ratios (ORs) of risk factors for UM
development or sufficient information to calculate them. Methodological quality
was evaluated using the Assessment of Multiple Systematic Reviews tool. RESULTS:
Four meta-analyses with a mean methodological quality score of 65.9% (min: 54.5%;
max: 72.7%) were included. The following significant risk factors were
identified: atypical cutaneous nevi (OR 2.82, 95% CI 1.10-7.26), welding (OR
2.05, 95% CI 1.20-3.51), occupational cooking (OR 1.81, 95% CI 1.33-2.46), fair
skin color (OR 1.80, 95% CI 1.31-2.47), light eye color (OR 1.75, 95% CI 1.31
2.34), common cutaneous nevi (OR 1.74, 95% CI 1.27-2.39), propensity to sunburn
(OR 1.64, 95% CI 1.29-2.09), iris nevi (OR 1.53, 95% CI 1.03-2.27), and cutaneous
freckles (OR 1.27, 95% CI 1.09-1.49). Non-significant factors included outdoor
leisure activity, occupational sunlight exposure, latitude of birth, and hair
color. CONCLUSION: Moderate quality of evidence determined nine significant risk
factors for developing UM. Knowledge of these variables will assist researchers
in the elaboration of a formal risk-assessment tool allowing clinicians to
estimate susceptibility to the disease and necessity of regular screening.
PMID- 28494169
TI - Companion Animals in Natural Disasters: A Scoping Review of Scholarly Sources.
AB - During a disaster, people may make evacuation decisions based on their companion
animal's welfare, therefore exposing themselves, their companion animals, and
emergency responders to increased risk for injury or death. The loss and
suffering of companion animals in disasters causes deep distress, diminishing
people's capacity to rebuild their lives. This scoping review presents scholarly
research studies and reviews relating to people and their companion animals in
the context of disasters, with an aim of informing researchers, policymakers, and
practitioners and providing direction for future research. Using the Arksey and
O'Malley framework, articles in scholarly journals from 2004 to 2014 are
discussed. Analysis included 38 articles: 20 research studies, 12 reviews, and 6
editorials. Findings revealed 2 central themes: companion animals as a risk
factor to human health and safety and companion animals being "at risk"
themselves. An emerging theme was "responsibility": Who is responsible for
companion animals in disasters and how? Understanding the implications of human
nonhuman animal relationships for disaster response and having a broader public
consensus on what is owed to animals at times of emergency are important to
community preparedness and resilience.
PMID- 28494170
TI - Why High-Intensity NPPV is Favourable to Low-Intensity NPPV: Clinical and
Physiological Reasons.
AB - High-intensity non-invasive positive pressure ventilation (NPPV) was originally
described for chronic hypercapnic chronic obstructive pulmonary disease (COPD)
patients in 2009, and refers to a specific ventilatory approach whereby NPPV
settings are aimed at achieving the lowest arterial partial pressure of carbon
dioxide (PaCO2) values possible. Thus, high-intensity NPPV requires ventilator
settings to be increased in a stepwise approach to either an individually
tolerated maximum, or to the levels necessary to achieve normocapnia. This
differs from the classic approach to low-intensity NPPV, which comprises
considerably lower ventilator settings and typically fails to lower elevated
PaCO2 values. The ongoing discussion about whether or not long-term NPPV should
be used in chronic hypercapnic COPD patients is based on the observation that
many studies in the last two decades have failed to provide evidence for this
particular patient cohort. In addition, these trials preferably used low
intensity NPPV. There is now, however, increasing evidence to suggest that high
intensity NPPV is capable of improving important physiological parameters such as
blood gases and lung function, as well as health-related quality of life.
Moreover, this approach also produced positive outcomes following two recent
randomized controlled trials, e.g., improved survival rates in stable COPD
patients, and admission-free survival in patients with persisting hypercapnia
following acute in-hospital NPPV to treat acute acidotic respiratory failure. As
a consequence, the time has now come to evaluate the impact of long-term NPPV on
both the physiological and clinical outcomes, with emphasis on the different
approaches to NPPV. Therefore, the aim of the current review article is to
elaborate on the clinical and physiological reasons for why high-intensity NPPV
is favourable to low-intensity NPPV.
PMID- 28494172
TI - An investigation of clear speech effects on articulatory kinematics in talkers
with ALS.
AB - Amyotrophic lateral sclerosis (ALS) affects the speech motor system and causes a
substantial decline in intelligibility. Clear speech strategies have been found
to benefit intelligibility in talkers with dysarthria and the purpose of this
study was to examine clear speech effects on tongue, lip, and jaw movements in
persons with ALS and healthy controls. For this purpose, participants produced 10
repetitions of the sentence 'I owe you a yoyo' using both habitual and clear
speech. Movement variability as well as maximum speed, range, and duration of
movement of the articulators were obtained for both conditions. The results show
significantly lower jaw movement variability during habitual speech but greater
variability for clear speech in ALS relative to controls. The kinematic data was
consistent with expectations for individuals with dysarthria. Based on these
results, clear speech may be considered a mode of speech that produces high
movement variability in talkers with ALS.
PMID- 28494171
TI - Zinc oxide nanoparticles antagonize the effect of Cetuximab on head and neck
squamous cell carcinoma in vitro.
AB - Zinc oxide nanoparticles (ZnO-NPs) are being used in many cosmetic products and
have been shown to induce tumor-selective cell death in human head and neck
squamous cell carcinoma (HNSCC) in vitro. Cetuximab is a monoclonal antibody
directed against the epidermal growth factor receptor (EGFR), whose effectiveness
for HNSCC, alone or in combination with cytostatic drugs, has been demonstrated
intensively in the last decades. Nanoparticles are known to interact with protein
structures and thus may influence their functionality. The aim of the current
study was to evaluate the effect of ZnO-NPs on the antitumor properties of
Cetuximab in HNSCC in vitro. Two HNSCC cell lines (FaDu and HLaC-78) were treated
with 0.1, 1 or 10 MUM Cetuximab as well as 0, 0.1 or 1 MUg/ml ZnO-NP. Qualitative
assessment of ZnO-NP was conducted via transmission electron microscopy (TEM) and
immunofluorescence staining. Evaluation was done via the MTT-assay after 24, 48
and 72 hours of incubation with Cetuximab and ZnO-NPs. ZnO-NPs were shown to
antagonize the anti-tumor effects of Cetuximab in a time-dependent as well as
dose-dependent way. These findings suggest an inhibitory interaction of ZnO-NPs
with Cetuximab, which warrants further investigation.
PMID- 28494173
TI - Suicide attempt with acetonitrile ingestion in a nursing mother.
AB - CONTEXT: Acetonitrile (ACN) is a solvent rapidly absorbed through lungs and
intestinal tract, and is slowly metabolized to cyanide (CN) by enzymatic
processes mediated by CYP2E1. OBJECTIVE: To describe the clinical and laboratory
evolution, ACN elimination half-life, and its presence in breast milk in a
nursing mother who attempted suicide. CASE DETAILS: A 25-year-old 2-month nursing
mother ingested an estimated dose of 2.1 g/kg of ACN. Blood and urine samples
were collected 24 h later for ACN, CN and thiocyanate analysis, and 12.5 g sodium
thiosulfate i.v. in 1-h infusion was started and repeated every 24 h for 4 days.
ACN results showed 200 mg/L in blood and 235 mg/L in urine. ACN analysis in the
breast milk at Day 6 showed level of 21 mg/L compared to 27 mg/L in blood
collected at the same time, suggesting a possible relationship of 1.3:1.0 ratio.
An elimination half-life of 40.4 h was calculated, compared to 32 and 36 h showed
in other studies. DISCUSSION: The clinical management must involve the use of CN
antidotes for more than 24 h depending on the symptoms and blood levels of ACN.
Furthermore, our data showed the possible existence of a close relationship
between plasma and breast milk levels.
PMID- 28494174
TI - Human endometrial stromal cell plasticity: Reversible sFlt1 expression negatively
coincides with decidualization.
AB - Preeclampsia (PE) is a major complication of pregnancy in which the placenta is
known to have shallow implantation into the uterine decidua. Studies have
implicated soluble fms-like tyrosine kinase-1 (sFlt1), a soluble vascular
endothelial growth factor (VEGF) receptor protein, in the pathogenesis of PE.
sFlt1 has the ability to bind to and neutralize the angiogenic functions of VEGF
and placental growth factor (PlGF). The presence of sFlt1 and its action in the
endometrium is yet to be determined. We hypothesize that endometrial stromal
cells (ESC) at the maternal-fetal interface may play a role in sFlt-1 regulation
during pregnancy. In this study, we seek to understand the dynamic regulation of
sFlt1 production in primary human ESC as a result of hormone stimulation and
withdrawal. To mimic a biphasic menstrual cycle, ESC were treated with cAMP to
induce endometrial decidualization that occurs during the luteal secretory phase,
followed by cAMP withdrawal reflecting the follicular proliferative phase. Here,
we present data to show that (1) ESC produce detectable amounts of sFlt1, (2)
sFlt1 expression is turned off during decidualization at both the protein and RNA
level (3) ESC decidualization and resulting sFlt1 expression are reversible
phenomenon, and (4) Decidualization markers prolactin (PRL) and VEGF expressions
in ESC are negatively correlated with sFlt1. These findings may have important
implications in diseases such as PE that involve abnormal decidualization,
implantation and angiogenesis at the maternal-fetal interface.
PMID- 28494175
TI - The effect of plasmapheresis on treating disseminated intravascular coagulation
(DIC) caused by a Hemiscorpius lepturus (Gadim) sting.
AB - INTRODUCTION: The highest mortality from scorpion stings in Iran is due to the
stings of a particular type of scorpion known as Hemiscorpius lepturus (H.
lepturus, Gadim in local language). The present study aimed at investigating the
use of plasmapheresis to treat severe cases of H. lepturus stings. METHOD: This
pilot study was a randomized clinical trial conducted from June 2015 to June 2016
in Razi hospital of Ahvaz, Iran. Twenty-nine patients who had been stung by H.
lepturus and admitted to ICU because of disseminated intravascular coagulation
(DIC) were randomly assigned into control (15 patients, supportive treatments)
and plasmapheresis (14 patients, supportive treatments + plasmapheresis) groups,
and the patient outcomes were compared between the two groups. FINDINGS: Eighteen
patients were female (62%), and the mean of patient age was 24 +/- 7. Most of the
sting cases had occurred in the torso (15 patients, 52%). Only 10 patients (34%)
arrived in the hospital within 12 h of being stung. There was no significant
difference between the two groups in terms of the demographic and sting features.
In the plasmapheresis group, hemoglobin level was significantly lower, while the
PT and INR were measurably higher. In total, the plasmapheresis group experienced
29 sessions of treatment (an average of two sessions for each patient). Overall,
19 patients (66%) expired, whereas 10 patients (34%) experienced recovery with or
without complications. The rate of recovery was significantly higher in the
plasmapheresis group compared with controls, with eight patients (57%) in the
plasmapheresis group surviving compared with two (14%) in the control group
(p=.045). The duration of hospitalization was higher in the plasmaphersis group
(p < .001). A comparison of the dead and recovered patients' features indicated
that the dead patients arrived in the hospital significantly later than the
recovered ones, and they also had lower platelet counts. CONCLUSIONS: The
findings of this small-scale pilot study show that using plasmapheresis in
treating DIC in patients stung by H. lepturus can prevent death and encourage
recovery. However, prior to using plasmapheresis as a routine treatment for
severe cases of people stung by this scorpion or other similar ones, further
controlled studies with a larger sample size are needed.
PMID- 28494177
TI - Influence of low-level laser on pain and inflammation in type 2 diabetes mellitus
with diabetic dermopathy - A case report.
AB - Numerous skin lesions have been commonly observed in individuals with diabetes
mellitus. The common skin manifestations of diabetes mellitus are erythrasma,
xanthomatosis, xanthelasma, phycomycetes and cutaneous infections like
furuncolosis, candidiasis, carbuncle, dermatophytosis, etc. Diabetic dermopathy
is the most common skin lesion found in patients with diabetes. It is typically
seen in men aged above 50 years. In low-level laser therapy (LLLT), the entire
lower limb was illuminated with the frequency of 20 Hz and wavelength of 830 nm
for 9 min, and the treatment was divided into four parts. With the continued
sessions of LLLT, the skin manifestations and neuropathy conditions improved
drastically. On the 21st day, the skin colour was found to be normal. Also, there
were significant changes in clinical findings for diabetic peripheral neuropathy.
LLLT with specific exercises can promote healing of skin manifestations in
individuals with type 2 diabetes mellitus. It can be used as an effective
treatment modality for treating diabetic dermopathy.
PMID- 28494176
TI - Comparative analysis of the effects of a sphingosine kinase inhibitor to
temozolomide and radiation treatment on glioblastoma cell lines.
AB - Glioblastoma multiforme (GBM) exhibits high resistance to the standard treatment
of temozolomide (TMZ) combined with radiotherapy, due to its remarkable cell
heterogeneity. Accordingly, there is a need to target alternative molecules
enhancing specific GBM autocrine or paracrine mechanisms and amplifying the
effect of standard treatment. Sphingosine 1-phosphate (S1P) is such a lipid
target molecule with an important role in cell invasion and proliferation.
Sphingosine kinase inhibitors (SKI) prevent S1P formation and induce increased
production of reactive oxygen species (ROS), which may potentiate radiation
cytotoxicity. We analyzed the effect of SKI singular versus combined treatments
with TMZ and radiation on 2 human GBM cell lines characterized by a lack of MGMT
expression and low or high expression of the anti-oxidant enzyme, glutathione
peroxidase 1 (GPx1). Effects were drug concentration-, cell line-dependent and
partly ROS-mediated. Clonogenic survival assay demonstrates that SKI was more
effective than TMZ in increasing the sensitivity of U87 cells, which express low
GPx1 amount, to a 2 Gy X-ray dose. Addition of both SKI and TMZ drastically
decreased U87 cells survival compared with the combination
temozolomide/radiation. SKI less effectively than TMZ sensitized LN229 cells to
the 2 Gy X-ray dose. Its combination to TMZ in absence of irradiation was as
efficient as TMZ combination with X-ray. We provide first evidence for SKI as an
alternative or complementary treatment to TMZ, and for efficient combinations of
low doses of drugs and X-ray. These may help as novel bi-modal and tri-modal
therapies to contend with GBM heterogeneity.
PMID- 28494178
TI - Suicide attempt with self-made Taxus baccata leaf capsules: survival following
the application of extracorporeal membrane oxygenation for ventricular arrythmia
and refractory cardiogenic shock.
AB - CONTEXT: Yew intoxication has been known for many years; high dose ingestion of
Taxus baccata leads to cardiac toxicity mediated by calcium and sodium channel
blocking properties. We present a case report of a patient who attempted suicide
after T. baccata ingestion, causing refractory cardiogenic shock requiring
temporary circulatory assistance by veno-arterial extra corporeal membrane
oxygenation (VA ECMO). CASE DETAILS: A 28-year-old man was admitted to the
critical care unit of a university hospital for arrhythmia after ingestion of
self-made T. baccata leaf capsules. He rapidly developed cardiovascular collapse
requiring mechanical ventilation, high dose intravenous catecholamines and
electrical cardioversion. A femoro-femoral VA ECMO was implanted due to severe
biventricular dysfunction and ventricular arrhythmia, associated with continuous
renal replacement therapy. Taxol A, taxol B and baccatin III were detected and
measured in both blood and urine samples by high-performance liquid
chromatography tandem mass spectrometry, and kinetics suggested urinary
excretion. Two days after hospital admission, VA ECMO and continuous renal
replacement therapy were removed with full recovery of cardiac function.
DISCUSSION: Our experience suggests that circulatory assistance by VA ECMO and
continuous renal replacement therapy seem to be effective safe second-line
therapeutic options in critically ill cases of severe yew intoxication with
refractory cardiogenic shock due to arrhythmia.
PMID- 28494179
TI - Predictive biomarkers for triple negative breast cancer treated with platinum
based chemotherapy.
AB - Treatment of triple negative breast cancer (TNBC) has been a big challenge since
it is defined. To date, platinum-based chemotherapy has played a significant role
in the treatment of TNBC patients. However, some patients do not respond to
platinum salts or gradually develop chemoresistance, resulting in little effect,
or even some adverse effects. Here, we review numerous preclinical and clinical
investigations to summarize possible mechanisms and potential predictive
biomarkers of platinum in TNBC. The homologous recombination deficiency (HRD)
resulting from the loss of BRCA function is the main rationale of platinum
efficacy in TNBC. BRCA mutation and methylation have been demonstrated to be
important potential biomarkers. Based on genome-wide effects, BRCA-like
classifier can identify the functional loss of BRCA and work as the predictor.
HRD score that is able to identify the "BRCAness" and predict the sensitivity of
platinum is increasingly considered. Taken together, all findings suggest that HR
deficiency profile encompassed by BRCA mutation and high HRD score could predict
response to platinum, even to other DNA-damage inducing agents. p53 family
members and molecular subtypes of TNBC are also important alternative
considerations for predicting platinum response based on the preclinical trials.
Currently, tumor infiltrating lymphocyte level and thrombocytopenia are emerging
as predictive biomarkers.
PMID- 28494181
TI - Characterization of Asthma-Chronic Obstructive Pulmonary Disease Overlap
Syndrome: A Qualitative Analysis.
AB - Approximately 15-20% of patients with chronic obstructive pulmonary disease
(COPD) also display characteristics of asthma. In May 2014, the asthma-COPD
overlap syndrome (ACOS) was briefly addressed in the Global Initiative for Asthma
(GINA) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy
documents. We evaluated how pulmonologists diagnose and treat ACOS and how they
assess its control. Pulmonologists from two university healthcare centers, having
>= 1 year experience, treating patients with asthma, COPD, or ACOS, were invited
to participate in focus groups. Two focus groups (1 hour duration) were convened
with seven and five participants, respectively. According to pulmonologists from
both institutions, ACOS is a new name for an existing syndrome rather than a new
disease. It is characterized by incomplete reversible airflow limitations and
changes in forced expiratory volume in one second over time. The pulmonologists
noted that its diagnosis must be based on clinical characteristics, pulmonary
function test results, and clinical intuition. To diagnose ACOS, pulmonologists
must rely on their clinical judgment. They also agreed that the treatment of
patients with ACOS should target the features of both asthma and COPD.
Pulmonologists from both institutions used asthma control criteria to assess ACOS
control. A deeper understanding would enable clinicians to establish specific
criteria for the diagnosis, treatment, and follow-up of subjects with ACOS.
PMID- 28494180
TI - Intra-arterial administration of tumor-targeting Salmonella typhimurium A1-R
regresses a cisplatin-resistant relapsed osteosarcoma in a patient-derived
orthotopic xenograft (PDOX) mouse model.
AB - Previously, a patient-derived orthotopic xenograft (PDOX) model was established
with a lung metastasis from an osteosarcoma patient which developed after
adjuvant cisplatinum (CDDP) treatment. In this model, we previously demonstrated
the efficacy of trabectedin (TRAB) and temozolomide (TEM) compared with CDDP. In
the present report, osteosarcoma tissue was implanted orthotopically in the
distal femur of mice which were randomized into the following groups when tumor
volume reached approximately 100 mm3; On day 14 after initiation of treatment,
all but CDDP significantly inhibited tumor volume growth compared with untreated
controls. Control (G1): 793.7 +/- 215.0 mm3; CDDP (G2): 588.1 +/- 176.9 mm3;
Salmonella typhimurium A1-R (S. typhimurium A1-R) intravenous (i.v.) (G3): 269.7
+/- 72.7 mm3; S. typhimurium A1-R intra-arterial (i.a.) (G4): 70.2 +/- 18.9 mm3
(CDDP: p = 0.056; S. typhimurium A1-R i.v.: p = 0.0001; S. typhimurium A1-R i.a.:
p = 0.00003, all vs. untreated controls). i.a. administration of S. typhimurium
A1-R was significantly more effective than either CDDP (p = 0.00007), or i.v.
administration of S. typhimurium A1-R (p = 0.00007) and significantly regressed
the tumor volume compared with day 0 (p = 0.001). The new model of i.a.
administration of S. typhimurium A1-R has great promise for the treatment of
recalcitrant osteosarcoma.
PMID- 28494182
TI - FabG can function as PhaB for poly-3-hydroxybutyrate biosynthesis in
photosynthetic cyanobacteria Synechocystis sp. PCC 6803.
AB - The production of poly-3-hydroxybutyrate (PHB) by photosynthetic cyanobacteria is
a potentially sustainable production method for the biodegradable plastics
industry. beta-Ketoacyl-ACP reductase (FabG), from the photosynthetic
cyanobacterium Synechocystis sp. PCC 6803 (SpFabG), is the first NADPH-dependent
reductase in the fatty acid biosynthesis pathway. Its structure is similar to
that of acetoacetyl-CoA reductase (SpPhaB), which is critical for PHB synthesis
and can replace SpPhaB for acetoacetyl-CoA reduction in vitro. However, the
specific function of SpFabG in fatty acid synthesis and whether SpFabG could
participate in PHB synthesis in vivo were not yet clear. In this study, the role
of SpFabG in fatty acid synthesis was first verified in vivo by knocking down and
overexpressing of fabG. It was shown that SpFabG was essential yet not rate
limiting for fatty acid biosynthesis. The biochemical characterization of SpFabG
using acetoacetyl-CoA as the substrate showed that the optimum temperature,
optimum pH, Km and kcat were 30 degrees C, 7, 2.30 mM, and 19.85 s-1,
respectively, which exemplified the ability of SpFabG to reduce acetoacetyl-CoA
with a relatively low affinity and weak catalytic efficiency. Functional analysis
of SpFabG in vivo indicated that SpFabG was able to partially complement SpPhaB
under nitrogen-deprived conditions, and overexpression of fabG led to the
diversion of partial carbon flux from fatty acid toward PHB synthesis.
PMID- 28494183
TI - Resolution of cannabis hyperemesis syndrome with topical capsaicin in the
emergency department: a case series.
AB - BACKGROUND: Cannabinoid hyperemesis syndrome (CHS) is characterized by symptoms
of cyclic abdominal pain, nausea, and vomiting in the setting of prolonged
cannabis use. The transient receptor potential vanilloid 1 (TRPV1) receptor may
be involved in this syndrome. Topical capsaicin is a proposed treatment for CHS;
it binds TRPV1 with high specificity, impairing substance P signaling in the area
postrema and nucleus tractus solitarius via overstimulation of TRPV1. This may
explain its apparent antiemetic effect in this syndrome. PURPOSE: We describe a
series of thirteen cases of suspected cannabis hyperemesis syndrome treated with
capsaicin in the emergency departments of two academic medical centers. METHODS:
A query of the electronic health record at both centers identified thirteen
patients with documented daily cannabis use and symptoms consistent with CHS who
were administered topical capsaicin cream for symptom management. RESULTS: All 13
patients experienced symptom relief after administration of capsaicin cream.
CONCLUSION: Topical capsaicin was associated with improvement in symptoms of CHS
after other treatments failed.
PMID- 28494184
TI - Current status of research and treatment for non-small cell lung cancer in never
smoking females.
AB - Lung cancer is the leading cause of cancer-related deaths worldwide with over 1
million deaths each year. The overall prognosis of lung cancer patients remains
unsatisfactory, with a 5-year overall survival rate of less than 15%. Although
most lung cancers are a result of smoking, approximately 25% of lung cancer cases
worldwide are not attributable to tobacco use. Notably, more than half of the
lung cancer cases in women occur in non-smokers. Among non-small-cell lung cancer
(NSCLC) cases, cigarette-smokers have a greater association with squamous cell
carcinoma than adenocarcinoma, which is more common in non-smokers. These
findings imply that specific molecular and pathological features may associate
with lung adenocarcinoma arising in non-smoker female patients. Over the past
decade, whole genome sequencing and other '-omics' technologies led to the
discovery of pathogenic mutations that drive tumor cell formation. These
technological developments may enable tailored patient treatments throughout the
course of their disease, potentially leading to improved patient outcomes. Some
clinical and laboratory studies have shown success outcomes using epidermal
growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine
kinase inhibitors (TKI) in patients with EGFR mutations and ALK rearrangements,
respectively. In fact, these 2 mutations are predominantly present in female non
smokers with adenocarcinoma. Immunotherapy has also recently emerged as a major
therapeutic modality in NSCLC. In this review, we summarize the current
understanding of NSCLC biology and new therapeutic molecular targets, focusing on
the pathogenesis of non-smoker female NSCLC patients.
PMID- 28494185
TI - Functional analysis of rare variants in mismatch repair proteins augments results
from computation-based predictive methods.
AB - The cancer-predisposing Lynch Syndrome (LS) arises from germline mutations in DNA
mismatch repair (MMR) genes, predominantly MLH1, MSH2, MSH6, and PMS2. A major
challenge for clinical diagnosis of LS is the frequent identification of variants
of uncertain significance (VUS) in these genes, as it is often difficult to
determine variant pathogenicity, particularly for missense variants. Generic
programs such as SIFT and PolyPhen-2, and MMR gene-specific programs such as PON
MMR and MAPP-MMR, are often used to predict deleterious or neutral effects of VUS
in MMR genes. We evaluated the performance of multiple predictive programs in the
context of functional biologic data for 15 VUS in MLH1, MSH2, and PMS2. Using
cell line models, we characterized VUS predicted to range from neutral to
pathogenic on mRNA and protein expression, basal cellular viability, viability
following treatment with a panel of DNA-damaging agents, and functionality in DNA
damage response (DDR) signaling, benchmarking to wild-type MMR proteins. Our
results suggest that the MMR gene-specific classifiers do not always align with
the experimental phenotypes related to DDR. Our study highlights the importance
of complementary experimental and computational assessment to develop future
predictors for the assessment of VUS.
PMID- 28494186
TI - Small interference ITGA6 gene targeting in the human thymic epithelium
differentially regulates the expression of immunological synapse-related genes.
AB - The thymus supports differentiation of T cell precursors. This process requires
relocation of developing thymocytes throughout multiple microenvironments of the
organ, mainly with thymic epithelial cells (TEC), which control intrathymic T
cell differentiation influencing the formation and maintenance of the
immunological synapse. In addition to the proteins of the major
histocompatibility complex (MHC), this structure is supported by several adhesion
molecules. During the process of thymopoiesis, we previously showed that laminin
mediated interactions are involved in the entrance of T-cell precursors into the
thymus, as well as migration of differentiating thymocytes within the organ.
Using small interference RNA strategy, we knocked-down the ITGA6 gene (which
encodes the CD49f integrin alpha-chain) in cultured human TEC, generating a
decrease in the expression of the corresponding CD49f subunit, in addition to
modulation in several other genes related to cell adhesion and migration.
Thymocyte adhesion to TEC was significantly impaired, comprising both immature
and mature thymocyte subsets. Moreover, we found a modulation of the MHC, with a
decrease in membrane expression of HLA-ABC, in contrast with increase in the
expression of HLA-DR. Interestingly, the knockdown of the B2M gene (encoding the
beta-2 microglobulin of the HLA-ABC complex) increased CD49f expression levels,
thus unraveling the existence of a cross-talk event in the reciprocal control of
CD49f and HLA-ABC. Our data suggest that the expression levels of CD49f may be
relevant in the general control of MHC expression by TEC and consequently the
corresponding synapse with developing thymocytes mediated by the T-cell receptor.
PMID- 28494187
TI - The screening of the functional microRNA binding site SNPs in sporadic colorectal
cancer genes.
AB - Sporadic colorectal cancer (sCRC) is one of the most commonly diagnosed cancers
worldwide, but few genetic markers have been identified and used for its early
detection. MicroRNAs are diverse cellular regulators in cancer pathogenesis that
bind to the 3'-untranslated region (3'-UTR) of their target mRNAs, and variants
within the miRNA target sites on sCRC-related genes may influence its
pathogenesis. To investigate this possibility, we used a bioinformatical method
to screen SNPs for putative changes in miRNA recognition sites within the 3'-UTR
of sCRC-related genes. The rs11466537 single nucleotide polymorphism was
predicted to modify the regulation of hsa-miR-1193 on the Transforming Growth
Factor beta Receptor II (TGFBR2) gene. Additionally, luciferase reporter assays
indicated that hsa-miR-1193 bound the T allele more strongly than the A allele of
rs11466537 (with A being the less frequent variant), and real time-polymerase
chain reaction and western blot analysis showed that TGFBR2 is significantly
repressed by hsa-miR-1193. Furthermore, overexpression of hsa-miR-1193 promoted
HT-29 cell proliferation, while the loss of hsa-miR-1193 inhibited the process.
Finally, the rs11466537 genotyping result revealed that the frequency of A allele
carriers was 1.5% in the control blood samples, but 0 in the sCRC patients'
normal colon tissue samples. Our results demonstrated that hsa-miR-1193 may be
involved in sCRC tumourigenesis at least in part by suppression of TGFBR2, and
the A allele of rs11466537 disturbed the regulation of hsa-miR-1193 on TGFBR2.
PMID- 28494188
TI - Depletion of signal recognition particle 72kDa increases radiosensitivity.
AB - The identification of genetic determinants that underpin tumor radioresistance
can help the development of targeted radiosensitizers or aid personalization of
radiotherapy treatment. Here we identify signal recognition particle 72kDa
(SRP72) as a novel gene involved in radioresistance. Knockdown of SRP72 resulted
in significant radiosensitization of HeLa (cervical), PSN-1 (pancreatic), and T24
(bladder), BT-549 (breast) and MCF7 (breast) tumor lines as measured by colony
formation assays. SRP72 depletion also resulted in the radiosensitization of
normal lung fibroblast cell lines (HFL1 and MRC-5), demonstrating that the effect
is not restricted to tumor cells. Increased radiosensitivity was not due to
impaired DNA damage signaling or repair as assessed by gamma-H2AX foci formation.
Instead SRP72 depletion was associated with elevated levels of apoptosis after
irradiation, as measured by caspase 3/7 activity, PARP-cleavage and Annexin-V
staining, and with an induction of the unfolded protein response. Together, our
results show that SRP72 is a novel gene involved in radioresistance.
PMID- 28494189
TI - Increased placental sFlt-1 but unchanged PlGF expression in late-onset
preeclampsia.
AB - OBJECTIVE: To investigate whether differences between late-onset preeclampsia
(PE) and intrauterine growth restriction (IUGR) can be explained by differential
placental expression patters of sFlt-1, Flt-1, and placental growth factor
(PlGF). METHODS: Placental tissues and maternal blood samples from seven patients
with PE, five IUGR, and seven age-matched controls were studied for mRNA and
protein levels as well as protein localization and expression intensity. RESULTS:
Placental PlGF mRNA and protein expression were not altered by placental
dysfunction while placental villous trophoblast expression intensity of PlGF was
increased. CONCLUSION: High sFlt-1 concentrations may account for diminished
maternal serum PlGF levels.
PMID- 28494190
TI - Formate-nitrite transporters: Monoacids ride the dielectric slide.
PMID- 28494191
TI - Biomarker for early renal microvascular and diabetic kidney diseases.
AB - Recognition of early stage of diabetic kidney disease, under common practice
using biomarkers, namely microalbuminuria, serum creatinine level above 1 mg/dL
and accepted definition of diabetic kidney disease associated with creatinine
clearance value below 60 mL/min/1.73 m2, is unlikely. This would lead to delay
treatment associated with therapeutic resistance to vasodilator due to a
defective vascular homoeostasis. Other alternative biomarkers related to the
state of microalbuminuria is not sensitive to screen for early diabetic kidney
disease (stages I, II). In this regard, a better diagnostic markers to serve for
this purpose are creatinine clearance, fractional excretion of magnesium (FE Mg),
cystatin C. Recently, renal microvascular disease and renal ischemia have been
demonstrated to correlate indirectly with the development of diabetic kidney
disease and its function. Among these are angiogenic and anti-angiogenic factors,
namely VEGF, VEGF receptors, angiopoietins and endostatin. With respect to
therapeutic prevention, implementation of treatment at early stage of diabetic
and nondiabetic kidney disease is able to restore renal perfusion and function.
PMID- 28494192
TI - Prooxidant-antioxidant balance, hsTnI and hsCRP: mortality prediction in
haemodialysis patients, two-year follow-up.
AB - Oxidative stress and inflammation are highly intertwined pathophysiological
processes. We analyzed the markers of these processes and high-sensitive troponin
I (hsTnI) for mortality prediction in patients on haemodialysis. This study
enrolled a total of 62 patients on regular haemodialysis. The patients were
monitored for two years, and the observed outcomes were all-cause and
cardiovascular mortality. Blood samples were taken before one dialysis session
for analysis of the baseline concentrations of prooxidant-antioxidant balance
(PAB), total antioxidant status (TAS), total oxidative status (TOS), hsTnI, hsCRP
and resistin. The overall all-cause mortality was 37.1% and CVD mortality 16.1%.
By univariate and multivariate logistic regression, our findings suggest that
good predictors of all-cause mortality include hsCRP and PAB (p < .05) and of CVD
mortality hsCRP (p < .05) and hsTnI (p < .001). To evaluate the relationship
between the combined parameter measurements and all-cause/CVD mortality risk,
patients were divided into three groups according to their PAB, hsCRP and hsTnI
concentrations. The cutoffs for hsCRP and hsTnI and the median for PAB were used.
Kaplan-Meier survival curves pointed out that the highest mortality risk of all
cause mortality was in the group with hsCRP levels above the cutoff and PAB
levels above the median (p < .001). The highest risk of CVD mortality was found
in the group with hsCRP and hsTnI levels above the cutoff levels (p = .001). Our
data suggest that hsCRP and PAB are very good predictors of all-cause mortality.
For CVD complications and mortality prediction in HD patients, the most sensitive
parameters appear to be hsTnI and hsCRP.
PMID- 28494194
TI - 17beta-Estradiol mineralization under field and laboratory incubations.
AB - Mineralization studies of natural steroid hormones (e.g., 17beta-estradiol, E2)
are performed in environmental incubators, usually under a constant temperature
such as 20 degrees C. In this paper, we present a microcosm protocol that
quantified the mineralization of E2 in soils under field temperatures. The nine
agricultural soils tested had a wide range of soil organic carbon (1.1 to 5.2%)
and clay (9 to 57%) contents. The calculated time over which half of the applied
E2 was mineralized (E2-1/2) ranged from 299 to 910 d, and total E2 mineralization
at 48 d (E2-TOT48) ranged from 4 to 13%. In subsequent laboratory incubations,
the same soils were incubated under a constant temperature of 20 degrees C, as
well as under cyclic temperatures of 14.5 degrees C (14 h) and 11.5 degrees C
(10h), which was within the temperature extremes observed in the field
microcosms. E2-1/2 ranged from 157 to 686 d at 20 degrees C and from 103 to 608 d
at the cyclic temperatures, with the E2-TOT48 ranging from 6 to 21% at 20 degrees
C and from 7 to 30% under cyclic temperatures. Despite the overall 6.75 degrees C
lower mean temperatures under the cyclic versus constant temperatures, E2
mineralization was stimulated by the temperature cycles in three soils.
Regardless of the incubation, the same loamy sand soil always showed larger E2
mineralization than the other eight soils and this loamy sand soil also had the
smallest E2 sorption. Current modeling approaches do not take into consideration
the effects of temperature fluctuations in the field because the input parameters
used to describe degradation are derived from laboratory incubations at a
constant temperature. Across the eight soils, E2-1/2 was on average 1.7 times
larger and E2-TOT48 was on average 0.8 times smaller under field temperatures
than under a constant 20 degrees C. Hence, we conclude that incubations at 20
degrees C give a reasonable representation of E2 mineralization occurring under
field conditions to be expected in a typical Prairie summer season.
PMID- 28494193
TI - Long-term trends in invasive pneumococcal disease in Manitoba, Canada.
AB - Invasive pneumococcal disease (IPD) remains a significant public health problem
in Manitoba, Canada although publically-funded pneumococcal conjugate (PCV7 and
PCV13) and polysaccharide (PPV23) vaccination programs exist. We analyzed routine
surveillance and administrative health data to examine trends in IPD rates as
these vaccines were introduced. Data on all individuals with a laboratory
confirmed diagnosis of IPD between 2001 and 2014 were obtained from the
provincial Communicable Diseases Surveillance database and linked with Manitoba's
provincial immunization registry and physician and hospital databases. We
calculated IPD incidence rates overall, by serotype and for different population
subgroups defined by socio-demographic and clinical (e.g., chronic diseases,
immune status) characteristics. Annual IPD incidence (95%CI) was 8.6 (8.2
9.1)/100,000 people during the study period (n = 1092), and rates were higher in
recent years and in regions with predominately indigenous populations. Reduction
in the incidence of serotypes included in PCV7 have been offset by rising rates
of PCV13-only serotypes in children, and more recently by rising rates of PPV
only serotypes and non-vaccine serotypes among young children and older adults
(>= 65 years). Rates were 3 times higher in those with a chronic disease and
highest (> 175-fold) among alcoholics, organ-transplant, and chronic kidney
failure patients. The case fatality rate was 12.0% within 30 d of diagnosis.
Despite the introduction of several vaccination programs, overall rates of IPD
have not declined in Manitoba in the last decade, due to increase in incidence of
non-PCV7 serotypes. A disproportionately high burden of disease impacts
indigenous communities and people with chronic disease.
PMID- 28494195
TI - Functionally inactivated dominant viral antigens of human cytomegalovirus
delivered in replication incompetent adenovirus type 6 vectors as vaccine
candidates.
AB - T cell immunity is critical in controlling human cytomegalovirus (HCMV) infection
in transplant recipients, and T cells targeting viral immediate early proteins
such as IE1, IE2 and pp65 have been speculated to be more effective against
reactivation. Here we report efforts to construct replication incompetent
adenovirus 6 vectors expressing these viral antigens as vaccine candidates. To
reduce the potential liabilities of these viral proteins as vaccine antigens, we
introduced mutations to inactivate their reported functions including their
nuclear localization signals. The modifications greatly reduced their
localization to the nuclei, thus limiting their interactions with cellular
proteins important for cell cycle modulation and transactivation. The
immunogenicity of modified pp65, IE1 and IE2 vaccines was comparable to their
wild-type counterparts in mice and the immunogenicity of the modified antigens
was demonstrated in non-human primates.
PMID- 28494197
TI - Learning Disabilities and Emotional Intelligence.
AB - The literature is conflicted around the subject of the emotional abilities of
individuals with Specific Learning Disabilities (SLDs): While many claim
cognitive challenges are associated with emotional difficulties, some suggest
emotional and interpersonal abilities are not compromised in such disorders and
may help individuals compensate and cope effectively with the challenges they
meet in learning environments. Two studies explored differences in emotional
intelligence (EI) between young adults with and without SLD. Two samples (matched
on gender, approximate age, and program of study; n = 100, and unmatched; n =
584) of college students took self-report and performance-based tests of EI
(Ability-EI) as well as a measure of self-esteem and demographics associated with
college performance (e.g.: SAT scores, gender, etc.). The results showed that
while SAT scores and ability emotional intelligence (Ability-EI) were associated
with college GPA, Ability-EI did not differ between the two groups, while self
report measures of EI and self-esteem did show differences, with the group with
learning disabilities ranking lower. The effects remained stable when we
controlled for demographics and potential intervening factors. The results
suggest that EI may play a protective role in the association between background
variables and college attainment in students with SLD. The results may provide a
basis for interventions to empower students with SLD in academia.
PMID- 28494196
TI - Misremembering Past Affect Predicts Adolescents' Future Affective Experience
During Exercise.
AB - PURPOSE: Increasing physical activity among adolescents is a public health
priority. Because people are motivated to engage in activities that make them
feel good, this study examined predictors of adolescents' feelings during
exercise. METHOD: During the 1st semester of the school year, we assessed 6th
grade students' (N = 136) cognitive appraisals of the importance of exercise.
Participants also reported their affect during a cardiovascular fitness test and
recalled their affect during the fitness test later that semester. During the 2nd
semester, the same participants rated their affect during a moderate-intensity
exercise task. RESULTS: Affect reported during the moderate-intensity exercise
task was predicted by cognitive appraisals of the importance of exercise and by
misremembering affect during the fitness test as more positive than it actually
was. This memory bias mediated the association between appraising exercise as
important and experiencing a positive change in affect during the moderate
intensity exercise task. CONCLUSION: These findings highlight the roles of both
cognitive appraisals and memory as factors that may influence affect during
exercise. Future work should explore whether affect during exercise can be
modified by targeting appraisals and memories related to exercise experiences.
PMID- 28494198
TI - MicroRNA-338 modulates cortical neuronal placement and polarity.
AB - The precise spatial and temporal regulation of gene expression orchestrates the
many intricate processes during brain development. In the present study we
examined the role of the brain-enriched microRNA-338 (miR-338) during mouse
cortical development. Reduction of miR-338 levels in the developing mouse cortex,
using a sequence-specific miR-sponge, resulted in a loss of neuronal polarity in
the cortical plate and significantly reduced the number of neurons within this
cortical layer. Conversely, miR-338 overexpression in developing mouse cortex
increased the number of neurons, which exhibited a multipolar morphology. All
together, our results raise the possibility for a direct role for this non-coding
RNA, which was recently associated with schizophrenia, in the regulation of
cortical neuronal polarity and layer placement.
PMID- 28494199
TI - Fine particulate matter (PM2.5) enhances allergic sensitization in BALB/c mice.
AB - Ambient particulate matter (PM), a component of air pollution, exacerbates airway
inflammation and hyperreactivity in asthmatic patients. Studies showed that PM
possesses adjuvant-like properties that enhance the allergic inflammatory
response; however, the mechanism (or mechanisms) by which PM enhances the
allergic response remains to be determined. The aim of this study was to assess
how exposure to fine PM collected from Sacramento, CA, shapes the allergic airway
immune response in BALB/c mice undergoing sensitization and challenge with
ovalbumin (OVA). Eight-week-old BALB/c male mice were sensitized/challenged with
phosphate-buffered saline (PBS/PBS; n = 6), PM/PBS (n = 6), OVA/OVA (n = 6), or
OVA + PM/OVA (n = 6). Lung tissue, bronchoalveolar lavage fluid (BALF), and
plasma were analyzed for cellular inflammation, cytokines, immunoglobulin E, and
heme oxygenase-1 (HO-1) expression. Mice in the OVA + PM/OVA group displayed
significantly increased airway inflammation compared to OVA/OVA animals. Total
cells, macrophages, and eosinophils recovered in BALF were significantly elevated
in the OVA + PM/OVA compared to OVA/OVA group. Histopathological grading
indicated that OVA + PM/OVA treatment induced significant inflammation compared
to OVA/OVA. Both immunoglobulin (Ig) E and tumor necrosis factor (TNF) alpha
levels were significantly increased in OVA/OVA and OVA + PM /OVA groups compared
to PBS/PBS control. The number of HO-1 positive alveolar macrophages was
significantly elevated in lungs of mice treated with OVA + PM /OVA compared to
OVA/OVA. Our findings suggest that fine PM enhances allergic inflammatory
response in pulmonary tissue through mechanisms involving increased oxidative
stress.
PMID- 28494200
TI - A new therapeutic potential for cancers: One CAR with 2 different engines!
AB - Tumor cells escape from immune recognition by several mechanisms such as down
regulating of MHC class I molecules, losing of tumor antigens, etc. The purpose
of cancer immunotherapy is to robust or reconstruct the capacity of the immune
system to recognize and kill tumor cells by overwhelming the mechanisms by which
tumors escape the immune response. One of the novel immunotherapeutic strategies
were used to potentiate NK- and T cell functions is chimeric antigen receptor
(CAR). CARs are composed of an antigen-binding domain of a molecule such as an
antibody (that binds to a tumor associated antigens expressed on the surface of
tumor cells) and an intracellular T cell activation domain. The CARs provide the
recognition of target antigen in a MHC-independent manner. CAR-armed T cells may
be unable to kill their targets in the absence of co-stimulators like NK cells.
On the other hand, CAR-armed NK cells may also be unable to destroy their targets
without receiving help signals from Th cells. Thus, if CAR-armed NK cells use
together with CAR-armed T cells, NK cells will be aggregated to the tumor site.
Thus, not only CAR T cells will obtain the necessary cytokines/costimulators from
NK cells, but also other tumor specific T cells will be primed by recognition of
tumor specific antigen (TSA) associated with MHC class I. These new specific
primed T cells probably combat against tumor cells which have lost their TAAs
that CAR-T cells are redirected to them.
PMID- 28494201
TI - Exploring sexual behaviors and health communication among older women.
AB - Older women around the globe are generally depicted as asexual beings, which may
impact patient-provider discussions about sex. We examined data on 703 aging
women in the United States to compare factors associated with women perceiving
sex as important and women discussing sex with their physicians since turning 50.
While 65.1% of participants perceived sex to be important, only 23.8% discussed
sex with their providers since turning 50. Factors related to discussing sex
included age, education, having a chronic condition, and consuming alcohol.
Provider training and tools about sexual health communication could help launch
those discussions about sex and increase advocacy for older women's sexual
health.
PMID- 28494202
TI - Abscisic acid signaling is involved in regulating the mitogen-activated protein
kinase cascade module, AIK1-MKK5-MPK6.
AB - Abscisic acid (ABA) plays roles in plant growth and development and in stress
responses. Recently, we found that ABA regulates ABA-insensitive protein kinase 1
(AIK1), a mitogen-activated protein kinase kinase kinase. Compared with wild
type, aik1-1 showed downregulation of ABA-responsive genes (RD29A, MYC2, ABI3 and
ABI4). Under ABA treatment, the transcript level of KRP1 (Kip-related protein, a
cyclin-dependent kinase inhibitor) was lower in aik1-1 than in wild-type. The
activity of ABA-activated MPK6 was decreased in abi1 abi2, and abi1 abi2 hab1,
and increased in snrk2.2 snrk2.3 and pyr1 pyl1 pyl2 pyl4 mutants. These results
indicated that AIK1-MKK5-MPK6 functions in ABA responses and requires ABA
responsive gene expression to regulate ABA-inhibited root growth and cell
division. The ABA signaling pathway regulates this MAPK cascade.
PMID- 28494203
TI - Carbofuran degraded by iron-doped anatase: Weakening the cholinesterase
inhibitory activity in the photoproducts mixture.
AB - Carbofuran is a toxic carbamate pesticide, and its use has increased in recent
years. While marketing information indicates stability in different chemical
media, carbofuran exhibits relative photolability. The aim of this research was
to decompose carbofuran and to identify the photoproducts achieved when two
different doped titania photocatalysts were employed under UV irradiation. The
iron-doped TiO2 materials were obtained (a) via a hydrothermal method and (b) by
an ultrasound-assisted sol-gel method. The precursors were TiOSO4?xH2O and
Fe3(NO3).9H2O. X-ray studies confirmed that the anatase phase of the iron-doped
TiO2 resulted from the two preparation methods. The photocatalytic performance of
the prepared materials was monitored by LC/ESI-QTOF-MS, enabling the
identification of photoproducts: oxo-carbamates, hydroxylated benzofuranes, a
carboxamide, and one amine. By using the iron-doped TiO2 materials, 2,2-dimethyl
2,3-dihydrobenzofuran-3,7-diol was the most abundant photoproduct, and N,2,2
trimethyl-2,3-dihydrobenzofuran-7-amine was the only compound that had not been
previously reported in the photolysis and photocatalysis of carbofuran. The
product 3-hydroxy carbofuran, a cholinesterase inhibitor, was quantified and was
found to be transformed into compounds that lack this inhibitive property.
PMID- 28494204
TI - Bio- and toxic elements in mushrooms from the city of Umea and outskirts, Sweden.
AB - Edible mushrooms (Albatrellus ovinus, Boletus edulis, Clitocybe odora, Gomphidius
glutinosus, Leccinum scabrum, Leccinum versipelle, Lycoperdon perlatum, Suillus
bovinus, Suillus luteus, and Xerocomus subtomentosus) collected from unpolluted
areas of the city of Umea and its outskirts in the northern part of Sweden were
examined for contents of toxic metallic elements (Cd, Pb, and Ag) and essential
macro- and microelements (K, Na, Ca, Mg, Cu, Fe, Mn, and Zn) using a validated
method and a final measurement by flame atomic absorption spectroscopy (F-AAS).
The median values of the toxic metallic element concentrations (in mg kg-1 dry
biomass, db) ranged from: 0.12-3.9, 0.46-5.1, and 0.91-6.2 for Ag, Cd and Pb,
respectively. For the essential metallic elements, the median values of
concentrations ranged from: 24000-58000, 15-2000, 59-610, 520-1900, 2.0-97, 16
150, 15-120, and 4.3-26 mg kg-1 db for K, Na, Ca, Mg, Cu, Zn, Fe, and Mn,
respectively. The baseline concentrations of the metallic elements determined in
mushrooms were mainly affected by the fungal species. The assessed probable
maximal dietary intake of Cd (0.002 mg kg-1 body mass) solely from a mushroom
meal was only slightly below a revised value of the tolerable weekly intake for
this element, while for Pb (0.003 mg kg-1 body mass) it was tenfold below the
provisionally tolerable weekly intake.
PMID- 28494205
TI - What determines supportive behaviors following bereavement? A systematic review
and call to action.
AB - Very few factors that impact the grieving process can be modified after the fact
to the extent that social support can. However, social support has received
limited research attention, resulting in little conceptual understanding of the
mechanisms behind perceptions of, and intentions to support, grieving persons.
This systematic review aimed to explore bereaved, decedent, and respondent
related determinants of the provision of social support. The review yielded 42
studies impacted by various methodological and sampling limitations. This review
poses a call to the field for more rigorous study of social support determinants
to better assist the bereaved and their natural supporters.
PMID- 28494206
TI - Component-resolved evaluation of the content of major allergens in therapeutic
extracts for specific immunotherapy of honeybee venom allergy.
AB - Allergen-specific immunotherapy is the only curative treatment of honeybee venom
(HBV) allergy, which is able to protect against further anaphylactic sting
reactions. Recent analyses on a molecular level have demonstrated that HBV
represents a complex allergen source that contains more relevant major allergens
than formerly anticipated. Moreover, allergic patients show very diverse
sensitization profiles with the different allergens. HBV-specific immunotherapy
is conducted with HBV extracts which are derived from pure venom. The allergen
content of these therapeutic extracts might differ due to natural variations of
the source material or different down-stream processing strategies of the
manufacturers. Since variations of the allergen content of therapeutic HBV
extracts might be associated with therapeutic failure, we adressed the component
resolved allergen composition of different therapeutic grade HBV extracts which
are approved for immunotherapy in numerous countries. The extracts were analyzed
for their content of the major allergens Api m 1, Api m 2, Api m 3, Api m 5 and
Api m 10. Using allergen-specific antibodies we were able to demonstrate the
underrepresentation of relevant major allergens such as Api m 3, Api m 5 and Api
m 10 in particular therapeutic extracts. Taken together, standardization of
therapeutic extracts by determination of the total allergenic potency might imply
the intrinsic pitfall of losing information about particular major allergens.
Moreover, the variable allergen composition of different therapeutic HBV extracts
might have an impact on therapy outcome and the clinical management of HBV
allergic patients with specific IgE to particular allergens.
PMID- 28494207
TI - Psychological Vulnerability and Gambling in Later Life.
AB - OBJECTIVES: Because behavioral problems often emerge from maladaptive coping
methods, we investigated whether unmet basic psychological needs evolve toward a
level of psychological vulnerability that puts older adults who gamble at risk
for becoming problem gamblers. METHODS: Data from a community sample of 379
adults ages 60 and above were analyzed using structural equation modeling.
Participants responded to items regarding their demographics, gambling frequency,
engagement in at-risk gambling behaviors, and the extent to which their basic
psychological needs were met. RESULTS: Satisfaction of basic psychological needs
among older adults who gamble was negatively associated with their being at risk
for developing a gambling problem. Satisfaction of basic psychological needs also
mediated the negative effect of socioeconomic status on at-risk gambling
behavior. CONCLUSION: Social workers should become mindful of how older adults,
who are confronting psychological vulnerabilities in later life, might well turn
to gambling as a maladaptive coping mechanism.As per journal style, abstract must
not exceed100 words. Please amend accordingly.
PMID- 28494208
TI - Silicon nanowires enhanced proliferation and neuronal differentiation of neural
stem cell with vertically surface microenvironment.
AB - Owing to its biocompatibility, noncytotoxicity, biodegradability and three
dimensional structure, vertically silicon nanowires (SiNWs) arrays are a
promising scaffold material for tissue engineering, regenerative medicine and
relevant medical applications. Recently, its osteogenic differentiation effects,
reorganization of cytoskeleton and regulation of the fate on stem cells have been
demonstrated. However, it still remains unknown whether SiNWs arrays could affect
the proliferation and neuronal differentiation of neural stem cells (NSCs) or
not. In the present study, we have employed vertically aligned SiNWs arrays as
culture systems for NSCs and proved that the scaffold material could promote the
proliferation and neuronal differentiation of NSCs while maintaining excellent
cell viability and stemness. Immunofluorescence imaging analysis, Western blot
and RT-PCR results reveal that NSCs proliferation and neuronal differentiation
efficiency on SiNWs arrays are significant greater than that on silicon wafers.
These results implicate SiNWs arrays could offer a powerful platform for NSCs
research and NSCs-based therapy in the field of neural tissue engineering.
PMID- 28494210
TI - Tobacco-Free Policy Compliance Behaviors among College Students: A Theory of
Planned Behavior Perspective.
AB - The purpose of this study was to examine the theory of planned behavior (TPB) as
a framework for understanding tobacco-free policy compliance behaviors.
Undergraduate student smokers (n = 479) on a college campus with a tobacco-free
policy were randomly selected to report their tobacco-free compliance behaviors
and respond to TPB items. A path analysis found all constructs of the TPB model
to be significantly related to tobacco-free policy compliance behaviors. The
results obtained from this study fill gaps in the mostly atheoretical literature
regarding our understanding of tobacco-free policy compliance behaviors as well
as extend our knowledge of the TPB. Implications for this study provide
recommendations for universities, health organizations, and government agencies
currently attempting to enforce compliance with a tobacco-free policy.
PMID- 28494209
TI - Antibiotic resistance, virulence factors and biofilm formation ability in
Escherichia coli strains isolated from chicken meat and wildlife in the Czech
Republic.
AB - Attachment of pathogenic bacteria to food contact surfaces and the subsequent
biofilm formation represent a serious threat for the food industry, since these
bacteria are more resistant to antimicrobials or possess more virulence factors.
The main aim of this study was to investigate the correlation between antibiotic
resistance against 13 antibiotics, distribution of 10 virulence factors and
biofilm formation in 105 Escherichia coli strains according to their origin. The
high prevalence of antibiotic resistance that we have found in wildlife isolates
could be acquired by horizontal transfer of resistance genes from human or
domestic or farm animals. Consequently, these commensal bacteria might serve as
indicator of antimicrobial usage for human and veterinary purposes in the Czech
Republic. Further, 46 out of 66 resistant isolates (70%) were able to form
biofilm and we found out statistically significant correlation between prevalence
of antibiotic resistance and biofilm formation ability. The highest prevalence of
antibiotic resistance was observed in weak biofilm producers. Biofilm formation
was not statistically associated with any virulence determinant. However, we
confirmed the correlation between prevalence of virulence factors and host
origin. Chicken isolates possessed more virulence factors (66%), than isolates
from wildlife (37%). We can conclude that the potential spread of antibiotic
resistance pattern via the food chain is of high concern for public health. Even
more, alarming is that E. coli isolates remain pathogenic potential with ability
to form biofilm and these bacteria may persist during food processing and
consequently lead to greater risks of food contamination.
PMID- 28494211
TI - Pecoramyces ruminantium, gen. nov., sp. nov., an anaerobic gut fungus from the
feces of cattle and sheep.
AB - The anaerobic gut fungi (AGF) inhabit the rumen and alimentary tracts of multiple
ruminant and nonruminant herbivores, belong to a distinct phylum-level lineage
(Neocallimastigomycota), and play an important role in plant biomass degradation
in many herbivores. As part of a wider effort to obtain AGF with high
lignocellulolytic capacities, we isolated and characterized four different AGF
strains from the feces of cattle and sheep. Microscopically, isolates produced
monocentric thalli and monoflagellated zoospores. Phylogenetic analysis revealed
that all isolates formed a monophyletic cluster with strong bootstrap support as
a sister clade to the genus Orpinomyces and close to Neocallimastix, an
unexpected result because these two genera of AGF form polyflagellated zoospores.
Isolates displayed a smooth biofilm-like growth in liquid medium and formed small
(0.5-1 mm) pinpoint circular colonies on agar roll tubes. Both endogenous and
exogenous sporangia were observed with variable shapes and sizes. Zoospores were
mainly spherical, with diameters ranging between 3.8 and 12.5 um, and mostly a
single flagellum. All strains exhibited similar substrate utilization patterns
and comparable cellulolytic and xylanolytic activities. Similar ITS1 sequences
falling within the same distinctive clade were found on GenBank, with all
environmental samples obtained from diverse ruminant and pseudoruminant hosts
from three continents, but not from any hindgut-fermenting hosts. Given the high
level of sequence divergence between our strains and closest cultured
representatives and their distinct microscopic/macroscopic features, we propose a
new genus, Pecoramyces, from the name of the taxonomic infraorder Pecora ("horned
ruminants" or "higher ruminants"; derived from the Latin word for horned
livestock), and a new species, P. ruminantium (since occurrence seems to be
specific to ruminant/pseudoruminant foregut, but not hindgut-fermenting mammals).
PMID- 28494212
TI - Retinal Toxicity of Acai Fruit (Euterpe Oleracea) Dye Concentrations in Rabbits:
Basic Principles of a New Dye for Chromovitrectomy in Humans.
AB - PURPOSE: Evaluate toxicity of acai fruit (Euterpe oleracea) dye concentrations in
a rabbit model. METHODS: Rabbits were injected intravitreously with 10%, 25%, and
35% acai dye concentrations. Control eyes received balanced salt solution (BSS).
Electroretinogram (ERG), fundus imaging, fluorescein angiography (FA), optical
coherence tomography (OCT), and light and transmission electron microscopy
(LM/TEM) were performed. RESULTS: Fundus imaging showed increased vitreous
opacity with increased dye concentrations. FA and OCT showed normality with all
concentrations. Comparisons between BSS and dye concentrations were analyzed
using Kruskal-Wallis and Mood's median test (p < 0.05). At 24 h, ERGs showed
reduced amplitudes from baseline in all eyes. Median b-wave amplitudes
nonsignificantly decreased and latency increased with 10% and 25%; findings were
significant (p < 0.05) for 35%. LM and TEM showed no abnormalities for 10% and
25%. With 35%, TEM showed ganglion cell edema at 24 h that resolved after 7 days.
Vacuolization, multilamellar bodies, and nerve bundle damage occurred at 24 h/7
days in the inner nuclear layer. Mitochondrial cristae disruption occurred in the
inner photoreceptor segment at 24 h that decreased by 7 days. CONCLUSION: Ten and
twenty-five percent concentrations were safe and may improve identification of
the posterior hyaloid and internal limiting membrane during chromovitrectomy in
humans.
PMID- 28494213
TI - Tumor-like microenvironment in oral lichen planus: evidence of malignant
transformation?
AB - INTRODUCTION: Oral lichen planus (OLP) is a T-cell-mediated chronic inflammatory
autoimmune disease affecting 0.1% to 4% of the world population. The WHO has
already recognized it as an oral potentially malignant disorder. However, the
reasons for the malignant transformation of OLP are far from being elucidated
clearly. The purpose of this review is to clarify how the tumor-like
microenvironment in OLP mediates its potentially malignant transformation. Areas
covered: We review published articles on the microenvironment characteristics of
tumors, the pathogenesis of OLP, and clinical studies of OLP. The main sources of
literature derive from MEDLINE/Pubmed and Thomson Reuter's Web of Science. Expert
commentary: The tumor-like microenvironment, including hypoxic, inflammatory,
immune and acid microenvironment, greatly contributes to carcinogenesis of OLP
patients. In order to effectively monitor the malignant transformation of OLP,
future studies should focus on long-term follow-up and select important detection
biomarkers.
PMID- 28494214
TI - The role and therapeutic targeting of IL-6 in rheumatoid arthritis.
AB - INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune chronic disease with
joint and systemic inflammation and it has been found that interleukin-6 (IL-6)
plays a key role in RA. Indeed, various clinical studies have proved that the
first-in-class IL-6 inhibitor, tocilizumab, a humanized anti-IL-6 receptor
monoclonal antibody, showed outstanding efficacy in RA. Areas covered: We review
here the role of IL-6 in the inflammatory conditions and how IL-6 contributes to
pathogenesis of RA, what induces IL-6 and how IL-6 expression is regulated.
Furthermore, clinical studies of tocilizumab for RA are summarized, Expert
commentary: We review and discuss the prospects for future applications of IL-6
targeting therapy and new therapeutic strategies targeting IL-6. Finally, we
discuss relevant issues with regard to the clinical management of IL-6 blockade
in RA.
PMID- 28494215
TI - Potential ultrastructure predicting factors for hepatocellular carcinoma in HCV
infected patients.
AB - Hepatitis C virus represents one of the rising causes of hepatocellular carcinoma
(HCC). Although the early diagnosis of HCC is vital for successful curative
treatment, the majority of lesions are diagnosed in an irredeemable phase. This
work deals with a comparative ultrastructural study of experimentally gradually
induced HCC, surgically resected HCC, and potential premalignant lesions from HCV
infected patients, with the prospect to detect cellular criteria denoting
premalignant transformation. Among the main detected pathological changes which
are postulated to precede frank HCC: failure of normal hepatocyte regeneration
with star shape clonal fragmentation, frequent elucidation of hepatic progenitor
cells and Hering canals, hepatocytes of different electron density loaded with
small sized rounded monotonous mitochondria, increase junctional complexes
bordering bile canaliculi and in between hepatocyte membranes, abundant cellular
proteinaceous material with hypertrophied or vesiculated rough endoplasmic
reticulum (RER), sequestrated nucleus with proteinaceous granular material or
hypertrophied RER, formation of lipolysosomes, large autophagosomes, and micro
vesicular fat deposition. In conclusion, the present work has visualized new
hepatocytic division or regenerative process that mimic splitting or clonal
fragmentation that occurs in primitive creature. Also, new observations that may
be of value or assist in predicting HCC and identifying the appropriate patient
for surveillance have been reported. Moreover, it has pointed to the possible
malignant potentiality of liver stem/progenitor cells. For reliability, the
results can be subjected to cohort longitudinal study.
PMID- 28494216
TI - Cough reflex hypersensitivity: A role for neurotrophins.
AB - Cough is one of the most common complaints for which sufferers seek medical
assistance. However, currently available drugs are not very effective in treating
cough, particularly that which follows an upper respiratory tract infection.
Nonetheless, there has been a significant increase in our understanding of the
mechanisms and pathways of the defensive cough as well as the
hypersensitive/pathophysiological cough, both at airway and central nervous
system (CNS) levels. Numerous molecules and signaling pathways have been
identified as potential targets for antitussive drugs, including neurotrophins
(NTs). NTs belong to a family of trophic factors and are critical for the
development and maintenance of neurons in the central and peripheral nervous
system including sympathetic efferents, sensory neuron afferents, and immune
cells. Nerve growth factor (NGF) was the first member of the NT family to be
discovered, with wide ranging actions associated with synapse formation,
survival, proliferation, apoptosis, axonal and dendritic outgrowth, expression
and activity of functionally important proteins such as ion channels, receptors,
and neurotransmitters. In addition, NGF has been implicated in several disease
states particularly neuropathic pain and most recently in the sensitization of
the cough reflex. This review will briefly address the peripheral and central
sensitization mechanisms of airway neurons and will then focus on NGF signaling
and its role in cough hypersensitivity.
PMID- 28494217
TI - Urinary IL-8 is a marker of early and long-term graft function after renal
transplantation.
AB - In this study, we examined whether the IL-8 content of urine sampled on day 1 and
day 14 after renal transplantation is a marker of early and long-term renal
function. Moreover, we assessed whether its concentration is positively
correlated with the matrix metalloproteinase-9 (MMP-9) content of urine sampled
on day 1 and day 30 and 12 months after renal transplantation. Our analysis
covered 87 patients who underwent a kidney transplant. The patients were observed
for an average of 30 months (12-60 months). The IL-8 concentration determined on
day 1 was significantly negatively correlated with creatinine clearance early
after renal transplantation (on days 1, 7, 14 and 30), as well as during long
term observations. IL-8 concentration in urine sampled on day 1 and day 14 was
higher in patients demonstrating DGF than in those without DGF. No relationship
was found between IL-8 content and cold ischaemia time. MMP-9 activity determined
on day 1 and month 3 after renal transplantation was positively correlated with
the IL-8 content determined in urine sampled on day 1, Rs = +0.32, p < .05 and Rs
= +0.31, p < .05, respectively. The results of this study suggest that a high IL
8 content in urine sampled on day 1 after renal transplantation is an
unfavourable marker of early and long-term (years-long) graft function. A high IL
8 content in urine sampled on day 1 after renal transplantation was positively
correlated with the activity of metalloproteinase-9 in urine. This proves that
both of these chemokines cooperate in ischaemia-reperfusion injuries in
transplanted kidneys.
PMID- 28494218
TI - Maternal cigarette smoking during pregnancy and offspring DNA methylation in
midlife.
AB - Maternal smoking in pregnancy (MSP) has been associated with DNA methylation in
specific CpG sites (CpGs) in infants and children. We investigated whether MSP,
independent of own personal active smoking, was associated with midlife DNA
methylation in CpGs that were previously identified in studies of MSP-DNA
methylation in children. We used data on MSP collected from pregnant mothers of
89 adult women born in 1959-1964 and measured DNA methylation in blood
(granulocytes) collected in 2001-2007 (mean age: 43 years). Seventeen CpGs were
differentially methylated by MSP, with multiple CpGs mapping to CYP1A1, MYO1G,
AHRR, and GFI1. These associations were consistent in direction with prior
studies (e.g., MSP associated with more and less methylation in AHRR and CYP1A1,
respectively) and, with the exception of AHRR CpGs, were not substantially
altered by adjustment for active smoking. These preliminary results confirm prior
prospective reports that MSP influences the offspring DNA methylation, and
extends the timeframe to midlife, and suggest that these effects may persist into
adulthood, independently of active smoking.
PMID- 28494219
TI - Oxidative degradation of tetramethylammonium hydroxide (TMAH) by UV/persulfate
and associated acute toxicity assessment.
AB - Tetramethylammonium hydroxide (TMAH) is widely used in high-tech industries as a
developing agent. Ultraviolet (UV) light-activated persulfate (PS, S2O82-) can be
used to generate strongly oxidative sulfate radicals, and it also exhibits the
potential to treat TMAH-containing wastewater. This study initially investigated
the effect of S2O82- concentration and UV strength on the UV/S2O82- process for
the degradation of TMAH in a batch reactor. The results suggested that 15 watts
(W) of UV-activated S2O82- at concentrations of 10 or 50 mM resulted in pseudo
first-order TMAH degradation rate constants of 3.1-4.2 * 10-2 min-1, which was
adopted for determining the hydraulic retention time (HRT) in a continuous
stirred tank reactor (CSTR). The operating conditions (15 W UV/10 mM S2O82-) with
a HRT of 129 min resulted in stable residual concentrations of S2O82- and TMAH at
approximately 2.6 mM and 20 mg L-1 in effluent, respectively. Several TMAH
degradation intermediates including trimethylamine, dimethylamine, and
methylamine were also detected. The effluent was adjusted to a neutral pH and
evaluated for its biological acute toxicity using Cyprinus carpio as a bioassay
organism. The "bio-acute toxicity unit" (TUa) was determined to be 1.41, which
indicated that the effluent was acceptable for being discharged into an aquatic
ecosystem.
PMID- 28494220
TI - Effects of Recombinant Human Lactoferrin on Osteoblast Growth and Bone Status in
Piglets.
AB - Lactoferrin (LF), an ~80 kDa iron-binding glycoprotein, modulates many biological
effects, including antimicrobial and immunomodulatory activities. Recently, it
was shown that LF also regulates bone cell activity, suggesting its therapeutic
effect on postmenopausal bone loss. However, a minimal amount is known regarding
the effects of recombinant human LF (rhLF) supplementation on bone status in
young healthy infants. We found osteoblast cell differentiation was significantly
promoted in vitro. Furthermore, treatment of human osteoblast cells with rhLF
rapidly induced phosphorylation of p44/p42 mitogen-activated protein kinase
(p44/p42 MAPK, ERK1/2). In order to investigate the effects of rhLF on bone
status in vivo, we used a piglet model, which is a useful model for human
infants. Piglets were supplemented with rhLF milk for 30 days. Bone formation
markers, Serum calcium concentration, bone mineral density (BMD), bone mineral
content (BMC), tibia bone strength, and the overall metabolite profile analysis
showed that rhLF was advantageous to the bone growth in piglets. These findings
suggest that rhLF supplementation benefits neonate bone health by modulating bone
formation.
PMID- 28494221
TI - Does copy number variation of APOL1 gene affect the susceptibility to focal
segmental glomerulosclerosis?
AB - BACKGROUND: APOL1 risk variants (G1 and G2) are associated with increased
susceptibility to focal segmental glomerulosclerosis (FSGS) in African
population. However, the two risk mutations were not found in Chinese FSGS
patients. In this study, we explored the association between the copy number
variation (CNV) of APOL1 gene and FSGS. METHODS: APOL1 copy number variations
were detected by quantitative real-time PCR with TaqMan probes and compared
between 133 FSGS patients and 123 controls. The association between CNV of APOL1
gene and clinical parameters was also investigated. RESULTS: The distribution of
APOL1 CNV did not show significant difference between FSGS patients and controls.
The creatinine and proteinuria in the high copy number group (CN >= 3) were
higher than the other two groups, but the difference was not significant (p >
.05). The FSGS pathological types were different among the three groups.
CONCLUSION: There was no significant difference in the distribution of APOL1 gene
copy variants between FSGS patients and normal controls, and there was no
significant correlation between the APOL1 gene CNV and the FSGS patients'
clinical manifestations. APOL1 CNVs may be not associated with susceptibility to
FSGS.
PMID- 28494222
TI - Distribution and incorporation mode of the herbicide MCPA in soil derived organo
clay complexes.
AB - The incorporation of xenobiotics into soil, especially via covalent bonds or
sequestration has a major influence on the environmental behavior including
toxicity, mobility, and bioavailability. The incorporation mode of 4-chloro-2
methylphenoxyacetic acid (MCPA) into organo-clay complexes has been investigated
under a low (8.5 mg MCPA/kg soil) and high (1000 mg MCPA/kg soil) applied
concentration, during an incubation period of up to 120 days. Emphasis was laid
on the elucidation of distinct covalent linkages between non-extractable MCPA
residues and humic sub-fractions (humic acids, fulvic acids, and humin). The
cleavage of compounds by a sequential chemical degradation procedure (OH-, BBr3,
RuO4, TMAH thermochemolysis) revealed for both concentration levels ester/amide
bonds as the predominate incorporation modes followed by ether linkages. A
possible influence of the soil microbial activity on the mode of incorporation
could be observed in case of the high level samples. Structure elucidation
identified MCPA as the only nonextractable substance, whereas the metabolite 4
chloro-2-methylphenol was additionally found as bioavailable and bioaccessible
compound.
PMID- 28494223
TI - Audiovisual integration supports face-name associative memory formation.
AB - Prior multisensory experience influences how we perceive our environment, and
hence how memories are encoded for subsequent retrieval. This study investigated
if audiovisual (AV) integration and associative memory formation rely on
overlapping or distinct processes. Our functional magnetic resonance imaging
results demonstrate that the neural mechanisms underlying AV integration and
associative memory overlap substantially. In particular, activity in anterior
superior temporal sulcus (STS) is increased during AV integration and also
determines the success of novel AV face-name association formation. Dynamic
causal modeling results further demonstrate how the anterior STS interacts with
the associative memory system to facilitate successful memory formation for AV
face-name associations. Specifically, the connection of fusiform gyrus to
anterior STS is enhanced while the reverse connection is reduced when
participants subsequently remembered both face and name. Collectively, our
results demonstrate how multisensory associative memories can be formed for
subsequent retrieval.
PMID- 28494224
TI - Trauma, Case Studies, and Dual Diagnosis Consequences.
PMID- 28494225
TI - What about me? The loss of self through the experience of traumatic childbirth.
AB - BACKGROUND AND OBJECTIVE: birth trauma has become an increasingly recognised
maternal mental health issue and has important implications for both mother and
infant. The importance of subjective birth experience in the development of birth
trauma has been identified and may mediate the lack of theoretical consistency in
this area. The current study aims to explore the subjective experience of birth
trauma among first time mothers in Ireland. It aims to separate the potential
effects of peripartum depression (PPD) from this in limiting this qualitative
investigation to women who reported birth trauma, without PPD. DESIGN: mixed
methods: Quantitative methods facilitated the recruitment of participants, the
selection of a homogenous sample and addressed previous methodological flaws in
birth trauma research. Interpretative Phenomenological Analysis (IPA) was used to
explore the subjective experience of traumatic childbirth. PARTICIPANTS: seven,
first- time mothers who reported a traumatic childbirth, without significant
symptoms of PPD participated. MEASUREMENT AND FINDINGS: screening measures of
birth trauma and PPD were completed by participants. A semi-structured interview
was then conducted with each participant about their childbirth experience.
Interviews were transcribed and analysed using IPA. The primary superordinate
theme recounted how the identity and individuality of women is ignored and
discounted, throughout the process of childbirth. Identity is challenged and
altered as a result of women's incompatibility with the maternity system.
CONCLUSIONS: this study supports the existence of birth trauma in an Irish
context and highlights the subjective experience of women as central to the
development of birth trauma. IMPLICATIONS FOR PRACTICE: acknowledgement and
inclusion of the mother as an individual throughout the process of childbirth may
be protective in limiting the experience of birth trauma.
PMID- 28494226
TI - The effect of prior experience on children's tool innovation.
AB - Spontaneous tool innovation to solve physical problems is difficult for young
children. In three studies, we explored the effect of prior experience with tools
on tool innovation in children aged 4-7years (N=299). We also gave children an
experience more consistent with that experienced by corvids in similar studies to
enable fairer cross-species comparisons. Children who had the opportunity to use
a premade target tool in the task context during a warm-up phase were
significantly more likely to innovate a tool to solve the problem on the test
trial compared with children who had no such warm-up experience. Older children
benefited from either using or merely seeing a premade target tool prior to a
test trial requiring innovation. Younger children were helped by using a premade
target tool. Seeing the tool helped younger children in some conditions. We
conclude that spontaneous innovation of tools to solve physical problems is
difficult for children. However, children from 4years of age can innovate the
means to solve the problem when they have had experience with the solution
(visual or haptic exploration). Directions for future research are discussed.
PMID- 28494227
TI - Spontaneous quorum sensing mutation modulates electroactivity of Pseudomonas
aeruginosa PA14.
AB - Pseudomonas aeruginosa is able to interact with the anode of a bioelectrochemical
system through redox active phenazines. Earlier studies showed that this
interaction is strain and carbon source dependent. With a spontaneously formed
DeltalasR mutant of P. aeruginosa PA14 and the wildtype, we investigated the
connection between the complex quorum sensing network and current production.
Depending on the carbon source, phenazine production and subsequently current
generation are effected differently in these two populations. In glucose-fed
cultures, the lack of the LasR regulator led to a shift in phenazine
concentration, relative composition, and time profiles. In contrast, with the
common fermentation product 2,3-butanediol as carbon substrate, no phenazine
production was detected for the DeltalasR mutant. For the wildtype, this carbon
source is known to induce phenazine synthesis and elevated current production.
This work supports the earlier hypothesis of a signaling link between 2,3
butanediol and the quorum-sensing regulatory system and extends this hypothesis
to predict a lasR-dependent interaction. The wildtype and mutant population were
also evaluated in direct competition, showing strong initial dominance of the
wildtype but a higher survival rate of the DeltalasR mutant in later stages of
growth. We found no evidence for strong social interactions between these two
subpopulations.
PMID- 28494228
TI - Enhanced oxygen reducing biocathode electroactivity by using sediment extract as
inoculum.
AB - Autotrophic bacteria are able to catalyze cathodic oxygen reduction as a
renewable and sustainable inexpensive catalyst. However, the performance of
biocathode varied over reactors, and we still not know how inoculums affect this
system. Using three different inoculum of wastewater (WW), sediment extract (SE)
and soil extract (SO) in parallel reactors, we found that SE achieved the
shortest setup time (17-25% shorter) as well as the highest power density
compared to those of SO and WW. Cyclic voltammetry (CV) further revealed that the
current densities of SE biocathodes (100+/-1A/m3) was 150% and 67% higher than
those of WW biocathodes (40+/-1A/m3) and SO biocathodes (65+/-1A/m3). Community
analysis showed the selective pressure on biocathode facilitated the growth of
Proteobacteria, Bacteroidetes, Firmicutes and Actinobacteria families. Different
from WW and SO biocathodes, Nitrospirae was selectively enriched in SE
biocathodes, corresponding to an obvious increase in Unidentified Nitrospiraceae
population at genus level, which may play an important role on the cathodic
electroactivity. These results confirmed that sediment extract is a better
bacteria source than soil and wastewater for the acclimation of autotrophic
electroactive bacteria, and the community comparison provided broader knowledge
on biocathode microbiology.
PMID- 28494229
TI - An algorithm for quantitatively modeling reflected ultrasonic bounded pulses and
beams.
AB - The study of the reflected acoustic waves plays an important role in our
understanding of media. We provide an algorithm to propagate the ultrasonic
bounded beam source and study its reflection from any horizontal and homogenous
water-solid boundary. This algorithm implements a hybrid combination of the phase
advance wavefield continuation in the frequency domain and the complex analytic
solution for the acoustic reflectivity. The peak amplitude of the specularly
reflected beam is in agreement with the laboratory measured acoustic reflection
from water-Aluminum and water-Copper alloy boundaries. The algorithm is able to
model the observed critical reflection as well as the null in the reflected
amplitude at the Rayleigh critical angle from the acoustic wave. This algorithm
is a crucial tool to understand the full reflected wave from material immersed in
water in any azimuthal or incidental angles. The software of this algorithm and
acoustic reflectivity from both solid materials are provided.
PMID- 28494230
TI - Study on chemical mechanical polishing of silicon wafer with megasonic vibration
assisted.
AB - Chemical mechanical polishing (CMP) is the primary method to realize the global
planarization of silicon wafer. In order to improve this process, a novel method
which combined megasonic vibration to assist chemical mechanical polishing (MA
CMP) is developed in this paper. A matching layer structure of polishing head was
calculated and designed. Silicon wafers are polished by megasonic assisted
chemical mechanical polishing and traditional chemical mechanical polishing
respectively, both coarse polishing and precision polishing experiments were
carried out. With the use of megasonic vibration, the surface roughness values Ra
reduced from 22.260nm to 17.835nm in coarse polishing, and the material removal
rate increased by approximately 15-25% for megasonic assisted chemical mechanical
polishing relative to traditional chemical mechanical polishing. Average Surface
roughness values Ra reduced from 0.509nm to 0.387nm in precision polishing. The
results show that megasonic assisted chemical mechanical polishing is a feasible
method to improve polishing efficiency and surface quality. The material removal
and finishing mechanisms of megasonic vibration assisted polishing are
investigated too.
PMID- 28494231
TI - HIV Latency Gets a New Histone Mark.
AB - Transcriptional latency of integrated HIV-1 provirus represents a major obstacle
to curing HIV. In this issue of Cell Host & Microbe, Boehm et al. (2017) identify
a new lysine methyltransferase that writes a repressive histone mark associated
with HIV-1 latency. The results are important for strategies to pharmacologically
reverse HIV-1 latency.
PMID- 28494232
TI - RAS and ROS-A Story of Pseudomonas Survival.
AB - Some pathogens block generation of reactive oxygen species to evade neutrophil
killing, but how that is accomplished is poorly understood. In this issue of Cell
Host & Microbe, Vareechon et al. (2017) describe ADP-ribosylation of Ras as a
strategy to inhibit assembly of neutrophil NADPH oxidase.
PMID- 28494233
TI - Don't Bite the Hand that Feeds You.
AB - Eukaryotic-bacterial symbioses are ubiquitous in nature. Pathogens and symbionts
employ similar machinery, yet symbionts can minimize host damage. In this issue
of Cell Host & Microbe, Enomoto et al. (2017) demonstrate how quorum sensing
regulates expression of virulence genes at appropriate times, thereby enabling
symbiont retention throughout the host lifespan.
PMID- 28494234
TI - An Elegan(t) Screen for Drug-Microbe Interactions.
AB - Microbes affect drug responses, but mechanisms remain elusive. Two papers in Cell
exploit C. elegans to infer anticancer drug mechanisms. Through high-throughput
screens of drug-microbe-host interactions, Garcia-Gonzalez et al. (2017) and
Scott et al. (2017) determine that bacterial metabolism underpins
fluoropyrimidine cytotoxicity, providing a paradigm for unraveling bacterial
mechanisms in drug metabolism.
PMID- 28494235
TI - ADE-ing and Abetting Zika.
AB - Although dengue virus (DENV) antibodies can neutralize or enhance Zika virus
(ZIKV) infection in vitro, their contribution to ZIKV infection in vivo remains
unclear. In a recent issue of Science, Bardina et al. (2017) explore the
protective versus pathogenic roles of DENV-immune antibodies in ZIKV infection
using a mouse model.
PMID- 28494236
TI - Allied Commensal Forces against Vancomycin-Resistant Enterococci.
AB - In this issue of Cell Host & Microbe, Caballero et al. (2017) define a precise,
limited consortium of commensal bacteria that restores resistance to colonization
by clinically vexing vancomycin-resistant Enterococcus species.
PMID- 28494237
TI - Microbial Vertical Transmission during Human Pregnancy.
AB - Congenital infections with pathogens such as Zika virus, Toxoplasma gondii,
Listeria monocytogenes, Treponema pallidium, parvovirus, HIV, varicella zoster
virus, Rubella, Cytomegalovirus, and Herpesviruses are a major cause of morbidity
and mortality worldwide. Despite the devastating impact of microbial infections
on the developing fetus, relatively little is known about how pathogens
associated with congenital disease breach the placental barrier to transit
vertically during human pregnancy. In this Review, we focus on transplacental
transmission of pathogens during human gestation. We introduce the structure of
the human placenta and describe the innate mechanisms by which the placenta
restricts microbial access to the intrauterine compartment. Based on current
knowledge, we also discuss the potential pathways employed by microorganisms to
overcome the placental barrier and prospects for the future.
PMID- 28494238
TI - SMYD2-Mediated Histone Methylation Contributes to HIV-1 Latency.
AB - Transcriptional latency of HIV is a last barrier to viral eradication. Chromatin
remodeling complexes and post-translational histone modifications likely play key
roles in HIV-1 reactivation, but the underlying mechanisms are incompletely
understood. We performed an RNAi-based screen of human lysine methyltransferases
and identified the SET and MYND domain-containing protein 2 (SMYD2) as an enzyme
that regulates HIV-1 latency. Knockdown of SMYD2 or its pharmacological
inhibition reactivated latent HIV-1 in T cell lines and in primary CD4+ T cells.
SMYD2 associated with latent HIV-1 promoter chromatin, which was enriched in
monomethylated lysine 20 at histone H4 (H4K20me1), a mark lost in cells lacking
SMYD2. Further, we find that lethal 3 malignant brain tumor 1 (L3MBTL1), a reader
protein with chromatin-compacting properties that recognizes H4K20me1, was
recruited to the latent HIV-1 promoter in a SMYD2-dependent manner. We propose
that a SMYD2-H4K20me1-L3MBTL1 axis contributes to HIV-1 latency and can be
targeted with small-molecule SMYD2 inhibitors.
PMID- 28494239
TI - CRISPR/Cas9 Screens Reveal Epstein-Barr Virus-Transformed B Cell Host Dependency
Factors.
AB - Epstein-Barr virus (EBV) causes endemic Burkitt lymphoma (BL) and
immunosuppression-related lymphomas. These B cell malignancies arise by distinct
transformation pathways and have divergent viral and host expression programs. To
identify host dependency factors resulting from these EBV+, B cell-transformed
cell states, we performed parallel genome-wide CRISPR/Cas9 loss-of-function
screens in BL and lymphoblastoid cell lines (LCLs). These highlighted 57 BL and
87 LCL genes uniquely important for their growth and survival. LCL hits were
enriched for EBV-induced genes, including viral super-enhancer targets. Our
systematic approach uncovered key mechanisms by which EBV oncoproteins activate
the PI3K/AKT pathway and evade tumor suppressor responses. LMP1-induced cFLIP was
found to be critical for LCL defense against TNFalpha-mediated programmed cell
death, whereas EBV-induced BATF/IRF4 were critical for BIM suppression and MYC
induction in LCLs. Finally, EBV super-enhancer-targeted IRF2 protected LCLs
against Blimp1-mediated tumor suppression. Our results identify viral
transformation-driven synthetic lethal targets for therapeutic intervention.
PMID- 28494240
TI - Cooperating Commensals Restore Colonization Resistance to Vancomycin-Resistant
Enterococcus faecium.
AB - Antibiotic-mediated microbiota destruction and the consequent loss of
colonization resistance can result in intestinal domination with vancomycin
resistant Enterococcus (VRE), leading to bloodstream infection in hospitalized
patients. Clearance of VRE remains a challenging goal that, if achieved, would
reduce systemic VRE infections and patient-to-patient transmission. Although
obligate anaerobic commensal bacteria have been associated with colonization
resistance to VRE, the specific bacterial species involved remain undefined.
Herein, we demonstrate that a precisely defined consortium of commensal bacteria
containing the Clostridium cluster XIVa species Blautia producta and Clostridium
bolteae restores colonization resistance against VRE and clears VRE from the
intestines of mice. While C. bolteae did not directly mediate VRE clearance, it
enabled intestinal colonization with B. producta, which directly inhibited VRE
growth. These findings suggest that therapeutic or prophylactic administration of
defined bacterial consortia to individuals with compromised microbiota
composition may reduce inter-patient transmission and intra-patient dissemination
of highly antibiotic-resistant pathogens.
PMID- 28494241
TI - Gut Microbiome Function Predicts Response to Anti-integrin Biologic Therapy in
Inflammatory Bowel Diseases.
AB - The gut microbiome plays a central role in inflammatory bowel diseases (IBDs)
pathogenesis and propagation. To determine whether the gut microbiome may predict
responses to IBD therapy, we conducted a prospective study with Crohn's disease
(CD) or ulcerative colitis (UC) patients initiating anti-integrin therapy
(vedolizumab). Disease activity and stool metagenomes at baseline, and weeks 14,
30, and 54 after therapy initiation were assessed. Community alpha-diversity was
significantly higher, and Roseburia inulinivorans and a Burkholderiales species
were more abundant at baseline among CD patients achieving week 14 remission.
Several significant associations were identified with microbial function; 13
pathways including branched chain amino acid synthesis were significantly
enriched in baseline samples from CD patients achieving remission. A neural
network algorithm, vedoNet, incorporating microbiome and clinical data, provided
highest classifying power for clinical remission. We hypothesize that the
trajectory of early microbiome changes may be a marker of response to IBD
treatment.
PMID- 28494242
TI - Pseudomonas aeruginosa Effector ExoS Inhibits ROS Production in Human
Neutrophils.
AB - Neutrophils are the first line of defense against bacterial infections, and the
generation of reactive oxygen species is a key part of their arsenal. Pathogens
use detoxification systems to avoid the bactericidal effects of reactive oxygen
species. Here we demonstrate that the Gram-negative pathogen Pseudomonas
aeruginosa is susceptible to reactive oxygen species but actively blocks the
reactive oxygen species burst using two type III secreted effector proteins, ExoS
and ExoT. ExoS ADP-ribosylates Ras and prevents it from interacting with and
activating phosphoinositol-3-kinase (PI3K), which is required to stimulate the
phagocytic NADPH-oxidase that generates reactive oxygen species. ExoT also
affects PI3K signaling via its ADP-ribosyltransferase activity but does not act
directly on Ras. A non-ribosylatable version of Ras restores reactive oxygen
species production and results in increased bacterial killing. These findings
demonstrate that subversion of the host innate immune response requires ExoS
mediated ADP-ribosylation of Ras in neutrophils.
PMID- 28494243
TI - A Rab20-Dependent Membrane Trafficking Pathway Controls M. tuberculosis
Replication by Regulating Phagosome Spaciousness and Integrity.
AB - The intracellular pathogen Mycobacterium tuberculosis (Mtb) lives within
phagosomes and also disrupts these organelles to access the cytosol. The host
pathways and mechanisms that contribute to maintaining Mtb phagosome integrity
have not been investigated. Here, we examined the spatiotemporal dynamics of Mtb
containing phagosomes and identified an interferon-gamma-stimulated and Rab20
dependent membrane trafficking pathway in macrophages that maintains Mtb in
spacious proteolytic phagolysosomes. This pathway functions to promote endosomal
membrane influx in infected macrophages, and is required to preserve Mtb
phagosome integrity and control Mtb replication. Rab20 is specifically and
significantly upregulated in the sputum of human patients with active
tuberculosis. Altogether, we uncover an immune-regulated cellular pathway of
defense that promotes maintenance of Mtb within intact membrane-bound
compartments for efficient elimination.
PMID- 28494244
TI - Quorum Sensing Attenuates Virulence in Sodalis praecaptivus.
AB - Sodalis praecaptivus is a close relative and putative environmental progenitor of
the widely distributed, insect-associated, Sodalis-allied symbionts. Here we show
that mutant strains of S. praecaptivus that lack genetic components of a quorum
sensing (QS) apparatus have a rapid and potent killing phenotype following
microinjection into an insect host. Transcriptomic and genetic analyses indicate
that insect killing occurs as a consequence of virulence factors, including
insecticidal toxins and enzymes that degrade the insect integument, which are
normally repressed by QS at high infection densities. This method of regulation
suggests that virulence factors are only utilized in early infection to initiate
the insect-bacterial association. Once bacteria reach sufficient density in host
tissues, the QS circuit represses expression of these harmful genes, facilitating
a long-lasting and benign association. We discuss the implications of the
functionality of this QS system in the context of establishment and evolution of
mutualistic relationships involving these bacteria.
PMID- 28494246
TI - Catalytic hydrodechlorination of triclosan using a new class of anion-exchange
resin supported palladium catalysts.
AB - We prepared a new class of anion-exchange-resin supported Pd catalysts for
efficient hydrodechlorination of triclosan in water. The catalysts were prepared
through an initial ion-exchange uptake of PdCl42- and subsequent reduction of
Pd(II) to Pd(0) nanoparticles at ambient temperature. Two standard strong-base
anion exchange resins (IRA-900 and IRA-958) with different matrices (polystyrene
and polyacrylic) were chosen as the supports. SEM and TEM images showed that
Pd(0) nanoparticles were evenly attached on the resin surface with a mean size of
3-5 nm. The resin supported Pd catalysts (Pd@IRA-900 and Pd@IRA-958) were able to
facilitate rapid and complete hydrodechlorination of triclosan. At a Pd loading
of 2.0 wt.%, the observed pseudo first-order rate constant (kobs) was 1.25 +/-
0.06 and 1.6 +/- 0.1 L/g/min for Pd@IRA-900 and Pd@IRA-958, respectively. The
catalysts were more resistant to Cl- poisoning and natural organic matter fouling
than other supported-Pd catalysts. The presence of 10 mM NaCl suppressed the kobs
value by 31% and 23% for Pd@IRA-900 and Pd@IRA-958, whereas the presence of humic
acid at 30 mg/L as TOC lowered the rates by 28% and 27%, respectively. The better
performance of Pd@IRA-958 was attributed to the polymeric matrix properties
(i.e., hydrophobicity, pore size, and surface area) as well as Pd particle size.
GC/MS analyses indicated that very low concentrations of chlorinated
intermediates were detected in the early stage of the hydrodechlorination
process, with 2-phenoxyphenol being the main byproduct. The catalysts can be
repeatedly used in multiple operations without significant bleeding. The
catalysts eliminate the need for calcination in preparing conventional supported
catalysts, and the resin supports conveniently facilitate control of Pd loading
and material properties.
PMID- 28494247
TI - Removal of micropollutants in biofilters: Hydrodynamic effects on biofilm
assembly and functioning.
AB - Global water resources contain a variety of micropollutants (MPs), including
pharmaceuticals, personal care products, and pesticides. This study investigated
the removal of MPs during drinking water production by means of biofiltration.
The objective of this work was to investigate the influence of hydrodynamics on
biofilm growth and development in a biofiltration process and the consequent
effect on MP biotransformation rates. We operated three groups of biofiltration
columns continuously for 381 days under three distinct hydrodynamic regimes
(superficial velocity: 10, 20, 40 cm h-1) and fed them a mixture of 29
micropollutants at low concentrations. Total protein concentrations were used as
a surrogate measurement for attached biomass and periodic tracer experiments were
conducted to estimate dispersivity and assess changes in the depth of the
biological zone in each biofilter. These data revealed significant differences in
biofilm assembly among the biofilters; higher superficial velocities led to less
concentrated surface biomass but a deeper biological zone and more total biomass.
Eleven of the 29 MPs were biotransformed and nine of those could be evaluated to
estimate biotransformation rates. The second-order rate constants for all nine
MPs were not significantly different among the hydrodynamic regimes. However, a
depth-based analysis of biotransformation rates revealed significantly greater
second-order rate constants for 5 of the MPs at increasing biofilter depths,
suggesting that sparse microbial communities found in deeper and more
oligotrophic biofilters had a greater activity for the biotransformation of these
MPs. The identification of several transformation products at similar relative
distributions suggests that the greater activity was not the result of changing
metabolic processes under more oligotrophic conditions. These results improve our
fundamental understanding of biofilm assembly and functioning in biofiltration
processes.
PMID- 28494248
TI - NLR diversity, helpers and integrated domains: making sense of the NLR IDentity.
AB - Plant innate immunity relies on genetically predetermined repertoires of immune
receptors to detect pathogens and trigger an effective immune response. A large
proportion of these receptors are from the Nucletoide Binding Leucine Rich Repeat
(NLR) gene family. As plants live longer than most pathogens, maintaining
diversity of NLRs and deploying efficient 'pathogen traps' is necessary to
withstand the evolutionary battle. In this review, we summarize the sources of
diversity in NLR plant immune receptors giving an overview of genomic, regulatory
as well as functional studies, including the latest concepts of NLR helpers and
NLRs with integrated domains.
PMID- 28494245
TI - Global Reprogramming of Host Kinase Signaling in Response to Fungal Infection.
AB - Cryptococcus neoformans (Cn) is a deadly fungal pathogen whose intracellular
lifestyle is important for virulence. Host mechanisms controlling fungal
phagocytosis and replication remain obscure. Here, we perform a global
phosphoproteomic analysis of the host response to Cryptococcus infection. Our
analysis reveals numerous and diverse host proteins that are differentially
phosphorylated following fungal ingestion by macrophages, thereby indicating
global reprogramming of host kinase signaling. Notably, phagocytosis of the
pathogen activates the host autophagy initiation complex (AIC) and the upstream
regulatory components LKB1 and AMPKalpha, which regulate autophagy induction
through their kinase activities. Deletion of Prkaa1, the gene encoding
AMPKalpha1, in monocytes results in resistance to fungal colonization of mice.
Finally, the recruitment of AIC components to nascent Cryptococcus-containing
vacuoles (CnCVs) regulates the intracellular trafficking and replication of the
pathogen. These findings demonstrate that host AIC regulatory networks confer
susceptibility to infection and establish a proteomic resource for elucidating
host mechanisms that regulate fungal intracellular parasitism.
PMID- 28494249
TI - Evaluation of problematic psychoactive substances use in people placed in police
custody.
AB - INTRODUCTION AND AIMS: In France, the law states that any person held in custody
could be examined by a doctor. The main objective of the medical examination is
to give medical evidence of health compatibility with custody. This review
identifies health risks such as addictive behaviour. We wanted to know which
psychoactive substances are used in this particular population, and how
problematic these uses are. DESIGN AND METHODS: A prospective, monocentric, open
ended study conducted via a structured questionnaire was carried out on detainees
who reported having taken drugs or illegal substances. Practitioners investigated
desired effects for each substance, and characteristics of use, by means of the
dependence criteria of the Diagnostic and Statistical Manual of Mental Disorders,
4th edition (American Psychiatric Association, 1994). Problematic use was
assessed when at least 3 items of the DSM IV were positive. RESULTS: 604
questionnaires were examined. 90.7% of questionnaires reported tobacco use, 76.2%
cannabis, 57.3% alcohol, 12.5% psychostimulants, 10.0% opiates and 0.7%
benzodiazepines or Z-drugs. The frequency of problematic use was 74.6% for
opiates, 44.9% for cocaine and 25.3% for cannabis. Compared to non-problematic
users, problematic users were older, more likely to be jobless without financial
means, more likely to have a medical history, including a greater likelihood of
mental illness, and more chance of undergoing prescribed medical treatment. They
included more women and more homeless people. DISCUSSION AND CONCLUSIONS: These
results show characteristics of psychoactive substance use in a sample of people
in custody. Psychoactive substances mentioned by respondents are not different
from those observed in the general population, but for certain users, the desired
effects are far from the pharmacologically expected ones. For some, taking
substances seems to be part of their way of life, for others it is a means to
compensate for an underlying feeling of uneasiness. Furthermore, problematic
users present severity criteria which seem to be greater than in psychoactive
substance users in the general population.
PMID- 28494250
TI - Recent developments of coumarin-containing derivatives and their anti-tubercular
activity.
AB - Tuberculosis (TB) is a lift-threatening chronic deadliest infectious disease
caused predominantly by Mycobacterium tuberculosis (MTB) which affects primarily
the lungs (pulmonary TB) apart from other vital organs. The emergence of drug
resistant TB (DR-TB), multidrug-resistant TB (MDR-TB), extensively drug-resistant
TB (XDR-TB) and the recently cases of totally drug resistant (TDR) towards
currently accessible standard drugs was increased up to alarming level in the
recent decades. In pursuit of searching new anti-TB agents, numerous of
derivatives have been synthesized and screened for their anti-TB activity.
Coumarins are one of the most important classes of natural products that
exhibited various biological activities, and their derivatives regarded as a new
class of effective anti-TB candidates owing to their potential anti-TB activity.
Thus, coumarin skeleton has attracted great interest in the development of new
anti-TB agents. This review outlines the advances in the application of coumarin
containing derivatives as anti-TB agents and the critical aspects of design and
structure-activity relationship of these derivatives.
PMID- 28494251
TI - Nitric oxide-releasing derivatives of brefeldin A as potent and highly selective
anticancer agents.
AB - A series of NO-donating mono- or diester derivatives of brefeldin A were
designed, synthesized and biologically evaluated. Some derivatives exhibited
potent antiproliferative activity with low IC50 values. The most potent NO
donating hybrid 13b exhibited stronger cytotoxicity against human prostate cancer
PC-3 cells, human colon carcinoma HT-29 cells and human liver cancer HepG-2 cells
than BFA with IC50 values of 25 nM, 160 nM and 180 nM, respectively. More
importantly, compound 13b showed good selectivity between human normal and tumor
liver cells with selectivity index of 33. Additionally, 13b released higher
levels of NO in HepG-2 cells than L-02 cells. Further mechanism concerning
cellular apoptosis showed that 13b induced apoptosis and S phase cell cycle
arrest in HepG-2 cells. Incubation with 13b increased the number of HepG-2 cells
with collapsed mitochondrial membrane at low concentrations in dose-dependent
manner. In addition, by using the Human Apoptosis Protein Array kit, several
apoptosis-related proteins, including HO-1, HO-2 and survivin, were found to be
markedly downregulated by 13b in HepG-2 cells. Furthermore, in western blot
assay, 13b increased the expression of Bax, Cyt c and caspase 3, and reduced the
relative levels of Bcl-2, Bcl-xl and pro-caspase 3 in HepG-2 cells.
PMID- 28494252
TI - Design, synthesis and primary biological evaluation of the novel 2-pyridone
derivatives as potent non-nucleoside HBV inhibitors.
AB - In continuation of our efforts toward the discovery of potent non-nucleoside
hepatitis B virus (HBV) inhibitors with novel structures, we have employed
bioisosterism and hybrid pharmacophore-based strategy to explore the chemically
diverse space of bioactive compounds. Cytotoxicity, anti-HBV antigen secretion
activities and anti-HBV DNA replication activity were assayed with cell counting
kit-8 (CCK-8), enzyme linked immunosorbent assay (ELISA) and a real-time PCR,
respectively. Some of the new compounds were able to inhibit the replication of
HBV DNA activity in the low micromolar range. In particular, compound 8u
displayed the most potent activity against the replication of HBV DNA with IC50
value of 3.4 MUM. The preliminary structure-activity relationship (SAR) of these
new compounds was investigated, which may help designing more potent molecules.
PMID- 28494253
TI - Structure-activity relationship study of the tumour-targeting peptide A20FMDV2
via modification of Lys16, Leu13, and N- and/or C-terminal functionality.
AB - The 20-residue linear peptide A20FMDV2 has been shown to exhibit high selectivity
and affinity for the tumour-related alphavbeta6 integrin and has potential as a
vector for therapeutic drugs. However, it exhibits poor half-life in plasma in
part due to its high susceptibility to serum proteases. In this study fourteen
A20FMDV2 analogues incorporating non-proteinogenic substitutes of the native
Lys16 and Leu13 residues and six A20FMDV2 analogues containing modified N- and C
termini were synthesised to increase the half-life and activity of A20FMDV2. The
analogues incorporating modified terminal motifs of A20FMDV2 were found to
strongly bind to the alphavbeta6 integrin and were subsequently functionalized
with the diethylenetriaminepentaacetic acid chelating agent to facilitate
coupling with radioactive indium-111 for human plasma stability and in vivo
biodistribution studies. A20FMDV2 peptide variants incorporating an N-terminal d
Asn and C-terminal d-Thr exhibited improved relative activity in vitro and were
less susceptible to plasma degradation.
PMID- 28494254
TI - Design, synthesis and antimicrobial evaluation of novel benzimidazole
incorporated sulfonamide analogues.
AB - A novel series of benzimidazole-incorporated sulfonamide analogues were designed
and synthesized with an effort to overcome the increasing antibiotic resistance.
Compound 5c gave potent activities against Gram-positive bacteria and fungi, and
2,4-dichlorobenzyl derivative 5g showed good activities against Gram-negative
bacteria. Both of these two active molecules 5c and 5g could effectively
intercalate into calf thymus DNA to form compound-DNA complex respectively, which
might block DNA replication to exert their powerful antimicrobial activity.
Molecular docking experiments suggested that compounds 5c and 5g could insert
into base-pairs of DNA hexamer duplex by the formation of hydrogen bonds with
guanine of DNA. The transportation behavior of these highly active compounds by
human serum albumin (HSA) demonstrated that the electrostatic interactions played
major roles in the strong association of active compounds with HSA, and which was
also confirmed by the full geometry calculation optimizations.
PMID- 28494255
TI - Design and synthesis of bis(indolyl)ketohydrazide-hydrazones: Identification of
potent and selective novel tubulin inhibitors.
AB - A novel series of ketohydrazide-hydrazones as analogues of naturally occurring
coscinamides has been synthesized and evaluated for their anticancer activity
against five cancer cell lines. Of the twenty-synthesized ketohydrazide
hydrazones, compounds, 21c, 21f, 21g, 21k and 21o showed cytotoxic effects (less
than 50% cell survival) against multiple cancer cell lines when tested at a final
concentration of 10 MUM. IC50 of three compounds 21f, 21k and 21o was determined
to be less than 5 MUM for all tested cancer cell lines. Compound 21k exhibited
significant anticancer activity against MCF-7, MDA-MB-231, HCT-116 and JURKAT
cancer cell lines with IC50 values of 0.8 MUM, 0.50 MUM, 0.15 MUM, and 0.22 MUM,
respectively. Also, 21k was found to be more selectively cytotoxic against tumor
cells when compared to normal cells. Preliminary mechanism of action studies
indicated that the most active compound 21k induced caspase-dependent apoptosis
in cells. 21k arrests cell cycle in G2/M phase by inhibiting of tubulin
polymerization (IC50 = 0.6 MUM).
PMID- 28494256
TI - Designing multi-targeted agents: An emerging anticancer drug discovery paradigm.
AB - The dominant paradigm in drug discovery is to design ligands with maximum
selectivity to act on individual drug targets. With the target-based approach,
many new chemical entities have been discovered, developed, and further approved
as drugs. However, there are a large number of complex diseases such as cancer
that cannot be effectively treated or cured only with one medicine to modulate
the biological function of a single target. As simultaneous intervention of two
(or multiple) cancer progression relevant targets has shown improved therapeutic
efficacy, the innovation of multi-targeted drugs has become a promising and
prevailing research topic and numerous multi-targeted anticancer agents are
currently at various developmental stages. However, most multi-pharmacophore
scaffolds are usually discovered by serendipity or screening, while rational
design by combining existing pharmacophore scaffolds remains an enormous
challenge. In this review, four types of multi-pharmacophore modes are discussed,
and the examples from literature will be used to introduce attractive lead
compounds with the capability of simultaneously interfering with different enzyme
or signaling pathway of cancer progression, which will reveal the trends and
insights to help the design of the next generation multi-targeted anticancer
agents.
PMID- 28494257
TI - Novel 1-(7-ethoxy-1-benzofuran-2-yl) substituted chalcone derivatives: Synthesis,
characterization and anticancer activity.
AB - Cancer treatment still requires new compounds to be discovered. Chalcone and its
derivatives exhibit anticancer potential in different cancer cells. A new series
of benzofuran substituted chalcone derivatives was synthesized by the base
catalyzed Claisen-Schmidt reaction of the 1-(7-ethoxy-1-benzofuran-2-yl) ethanone
with different aromatic aldehydes to yield 1-(7-ethoxy-1-benzofuran-2-yl)
substituted chalcone derivatives 3a-j. The derivatives were characterized by
elemental analysis, FT-IR, 1H NMR and 13C NMR spectroscopy techniques. The anti
growth effect of chalcone compounds was tested in breast cancer (MCF-7), non
small cell lung cancer (A549) and prostate cancer (PC-3) cell lines by the SRB
and ATP cell viability assays. Apoptosis was detected by mitochondrial membrane
potential, Annexin V staining and caspase 3/7 activity. Formation of reactive
oxygen species was determined by DCFDA. The results revealed that chalcone
derivatives have anticancer activity with especially chalcone derivative 3a
showing cytotoxic effects on cancer cells. In addition, chalcone derivative 3a
induced apoptosis through caspase dependent pathways in prostate, lung and breast
cancer cells.
PMID- 28494258
TI - Stress-related psychosocial factors at work, fatigue, and risky driving behavior
in bus rapid transport (BRT) drivers.
AB - INTRODUCTION: There is consistent scientific evidence that professional drivers
constitute an occupational group that is highly exposed to work related
stressors. Furthermore, several recent studies associate work stress and fatigue
with unsafe and counterproductive work behaviors. This study examines the
association between stress-related work conditions of Bus Rapid Transport (BRT)
drivers and risky driving behaviors; and examines whether fatigue is a mechanism
that mediates the association between the two. METHOD: A sample of 524 male Bus
Rapid Transit (BRT) operators were drawn from four transport companies in Bogota,
Colombia. The participants answered a survey which included an adapted version of
the Driver Behavior Questionnaire (DBQ) for BRT operators, as well as the Effort
Reward Imbalance and Job Content Questionnaires, the Subjective Fatigue subscale
of the Checklist Individual Strength (CIS) and the Need for Recovery after Work
Scale (NFR). RESULTS: Utilizing Structural Equation Models (SEM) it was found
that risky driving behaviors in BRT operators could be predicted through job
strain, effort-reward imbalance and social support at work. It was also found
that fatigue and need for recovery fully mediate the associations between job
strain and risky driving, and between social support and risky driving, but not
the association between effort/reward imbalance (ERI) and risky driving.
CONCLUSIONS: The results of this study suggest that a) stress related working
conditions (Job Strain, Social Support and ERI) are relevant predictors of risky
driving in BRT operators, and b) that fatigue is the mechanism which links
another kind of stress related to working conditions (job strain and low social
support) with risky driving. The mechanism by which ERI increases risky driving
in BRT operators remains unexplained. PRACTICAL APPLICATIONS: This research
suggests that in addition to the individual centered stress-reduction
occupational programs, fatigue management interventions aimed to changing some
working conditions may reduce risky driving behaviors and promote safety in the
professional drivers' jobs and on the road.
PMID- 28494259
TI - Mechanisms underlying cognitive conspicuity in the detection of cyclists by car
drivers.
AB - OBJECTIVE: The aim of this study was to evaluate the visibility of cyclists for
motorists in a simulated car driving task. BACKGROUND: In several cases involving
collisions between cars and cyclists, car drivers failed to detect the latter in
time to avoid collision because of their low conspicuity. METHOD: 2 groups of
motorists (29.2 years old), including 12 cyclist-motorists and 13 non-cyclist
motorists, performed a vulnerable road user detection task in a car-driving
simulator. They had to detect cyclists and pedestrians in an urban setting and
evaluate the realism of the cyclists, the traffic, the city, the infrastructure,
the car driven and the situations. Cyclists appeared in critical situations
derived from previous accounts given by injured cyclists and from cyclists'
observations in real-life situations. Cyclist's levels of visibility for car
drivers were either high or low in these situations according to the cyclists.
RESULTS: Realism scores were similar and high in both groups. Cyclist-motorists
had fewer collisions with cyclists and detected cyclists at a greater distance in
all situations, irrespective of cyclist visibility. Several mechanisms underlying
the cognitive conspicuity of cyclists for car drivers were considered.
CONCLUSION: The attentional selection of a cyclist in the road environment during
car driving depends on top-down processing. APPLICATION: We consider the
practical implications of these results for the safety of vulnerable road users
and future directions of research.
PMID- 28494260
TI - Examination of the reliability of the crash modification factors using empirical
Bayes method with resampling technique.
AB - There have been plenty of studies intended to use different methods, for example,
empirical Bayes before-after methods, to get accurate estimation of CMFs. All of
them have different assumptions toward crash count if there was no treatment.
Additionally, another major assumption is that multiple sites share the same true
CMF. Under this assumption, the CMF at an individual intersection is randomly
drawn from a normally distributed population of CMFs at all intersections. Since
CMFs are non-zero values, the population of all CMFs might not follow normal
distributions, and even if it does, the true mean of CMFs at some intersections
may be different from that at others. Therefore, a bootstrap method based on
before-after empirical Bayes theory was proposed to estimate CMFs, but it did not
make distributional assumptions. This bootstrap procedure has the added benefit
of producing a measure of CMF stability. Furthermore, based on the bootstrapped
CMF, a new CMF precision rating method was proposed to evaluate the reliability
of CMFs. This study chose 29 urban four-legged intersections as treated sites,
and their controls were changed from stop-controlled to signal-controlled.
Meanwhile, 124 urban four-legged stop-controlled intersections were selected as
reference sites. At first, different safety performance functions (SPFs) were
applied to five crash categories, and it was found that each crash category had
different optimal SPF form. Then, the CMFs of these five crash categories were
estimated using the bootstrap empirical Bayes method. The results of the
bootstrapped method showed that signalization significantly decreased Angle+Left
Turn crashes, and its CMF had the highest precision. While, the CMF for Rear-End
crashes was unreliable. For KABCO, KABC, and KAB crashes, their CMFs were proved
to be reliable for the majority of intersections, but the estimated effect of
signalization may be not accurate at some sites.
PMID- 28494261
TI - Relationship between physical performance and self-reported function in healthy
individuals across the lifespan.
AB - BACKGROUND: Functional outcome measures in clinical trials of musculoskeletal
conditions need to be meaningful to individuals. OBJECTIVES: To investigate the
relationship between physical performance and self/proxy-reported function in
1000 healthy children and adults. DESIGN: Cross-sectional observational study
(1000 Norms Project). METHODS: One thousand males and females aged 3-101 years,
healthy by self-report and without major physical disability, were recruited.
Twelve performance-based tests were analysed: vertical and long jump, two hand
dexterity tests, four balance tests, stepping reaction time, 30-second chair
stand, timed up-and-down stairs, and six-minute walk. Self/proxy-reported
function was assessed using the Infant-Toddler Quality of Life questionnaire,
Child Health Questionnaire, Assessment of Quality of Life (AQoL)-6D Adolescent,
AQoL-8D, International Physical Activity Questionnaire and work ability question.
Bivariate and multivariate correlational analyses were constructed for infants (3
4y), children (5-10y), adolescents (11-17y), adults (18-59y) and older adults
(60+). RESULTS/FINDINGS: Socio-demographic characteristics were similar to the
Australian population. Among infants/children, greater jump and sit-to-stand
performance correlated with higher proxy-reported function (p < 0.05). There were
no significant relationships observed for adolescents (p > 0.05). Greater jump,
dexterity, balance, reaction time, sit-to-stand, stair-climbing and six-minute
walk performance correlated with higher self-reported function in adults (r =
0.097 to.231; p < 0.05) and older adults (r = -0.135 to 0.625; p < 0.05).
Multivariate regression modelling revealed a collection of independent
performance measures explaining up to 46% of the variance in self/proxy-reported
function. CONCLUSIONS: Many performance-based tests were significantly associated
with self/proxy-reported function. We have identified a set of physical measures
which could form the basis of age-appropriate functional scales for clinical
trials of musculoskeletal conditions.
PMID- 28494262
TI - Repositioning error, pressure pain threshold, catastrophizing and anxiety in
adolescents with chronic idiopathic neck pain.
AB - BACKGROUND: Impaired proprioception, increased pain sensitivity, higher levels of
anxiety and catastrophizing are present in adults with chronic idiopathic neck
pain. Despite the high prevalence of neck pain, studies in adolescents are
scarce. OBJECTIVES: The main aim was to compare pressure pain thresholds (PPTs)
and joint repositioning error (JRE) between adolescents with chronic idiopathic
neck pain and adolescents without neck pain. Secondary aims were to compare these
groups for catastrophizing and anxiety and to investigate the association between
PPTs, JRE and psychosocial variables and pain characteristics. METHODS: 80
adolescents (40 with and 40 without chronic neck pain) were assessed for: neck
repositioning error, neck, upper trapezius and tibialis anterior PPTs, anxiety
and catastrophizing. Neck pain was characterized in terms of intensity,
frequency, duration and associated disability. MANCOVA was used for between group
comparisons and Pearson and Spearman coefficients for correlational analysis.
RESULTS: Adolescents with neck pain showed higher levels of catastrophizing (p <
0.001) and anxiety (trait: p < 0.001; state: p = 0.028), lower PPTs (p < 0.001)
and higher JRE (p < 0.001) than asymptomatic controls. Pain intensity, frequency
and duration were moderately correlated with anxiety, and disability was
moderately correlated with anxiety (r between 0.43 and 0.50, p < 0.05) and
catastrophizing (r = 0.40, p < 0.05). CONCLUSIONS: This study suggests that
functional changes and maladaptive cognitive processes are present in adolescents
with neck pain aged 16-18 years old. These findings need to be replicated in
future studies.
PMID- 28494263
TI - Zipf's Law of Abbreviation and the Principle of Least Effort: Language users
optimise a miniature lexicon for efficient communication.
AB - The linguist George Kingsley Zipf made a now classic observation about the
relationship between a word's length and its frequency; the more frequent a word
is, the shorter it tends to be. He claimed that this "Law of Abbreviation" is a
universal structural property of language. The Law of Abbreviation has since been
documented in a wide range of human languages, and extended to animal
communication systems and even computer programming languages. Zipf hypothesised
that this universal design feature arises as a result of individuals optimising
form-meaning mappings under competing pressures to communicate accurately but
also efficiently-his famous Principle of Least Effort. In this study, we use a
miniature artificial language learning paradigm to provide direct experimental
evidence for this explanatory hypothesis. We show that language users optimise
form-meaning mappings only when pressures for accuracy and efficiency both
operate during a communicative task, supporting Zipf's conjecture that the
Principle of Least Effort can explain this universal feature of word length
distributions.
PMID- 28494265
TI - Intramyocardial fate and effect of iron nanoparticles co-injected with MACS(r)
purified stem cell products.
AB - BACKGROUND: Magnetic activated cell sorting (MACS(r)) is routinely used to
isolate stem cell subpopulations intended for the treatment of cardiovascular
diseases. In strong contrast, studies examining the amount, effect and
intramyocardial distribution of iron nanoparticles used for magnetic cell
labelling are missing, although iron excess can cause functional disorders in the
heart. METHODS AND RESULTS: CD133+ haematopoietic and CD271+ mesenchymal stem
cells were purified from bone marrow using automatically and manually MACS(r)
based systems. Flow cytometric measurements demonstrated a rapid loss of MACS(r)
MicroBeads from cells under culture conditions, while storage under hypothermic
conditions decelerated their detachment. Moreover, an average loading of ~11 fg
iron/cell caused by magnetic labelling was determined in magnetic particle
spectroscopy. Importantly, hemodynamic measurements as well as histological
examinations using a myocardial ischemia/reperfusion mouse model showed no
influence of MACS(r) MicroBeads on cardiac regeneration, while the
transplantation of stem cells caused a significant improvement. Furthermore,
immunostainings demonstrated the clearance of co-injected iron nanoparticles from
stem cells and the surrounding heart tissue within 48 h post transplantation.
CONCLUSIONS: Our results indicate that iron amounts typically co-injected with
MACS(r) purified stem cells do not harm cardiac functions and are cleared from
heart tissue within a few hours. Therefore, we conclude that MACS(r) MicroBeads
exhibit a good compatibility in the cardiac environment.
PMID- 28494266
TI - Pelvic organ prolapse surgery in Finland from 1987 to 2009: A national register
based study.
AB - OBJECTIVES: To establish the trends in pelvic floor surgery in Finnish female
population and to evaluate the age-specific incidence as well as the lifetime
risk for pelvic organ prolapse surgery. STUDY DESIGN: We conducted a population
based register study, which includes all Finnish women (n=77 906), who underwent
surgery for pelvic organ prolapse in Finland 1987-2009. The women were identified
in the Care Register for Health Care based on the procedure codes. Number of
procedures, age-adjusted incidence, age-specific incidence, cumulative incidence,
lifetime risk were calculated. RESULTS: A total of 93 226 surgical procedures for
POP were performed. The age-adjusted incidence of prolapse surgery was 1.3/1000
women in 1987. After that there was an increase which peaked in 1996 with
1.9/1000, and a decline thereafter back to 1.3/1000 in 2009. The lifetime risk
for a woman to have undergone at least one surgical procedure for prolapse was
12.8%. Surgery was most common within women aged 70 to 79 years, followed by
women aged 60 to 69 years. The most popular procedure until 1991 was cervix
amputation with colporraphies, surpassed thereafter by colporraphies only or with
combined vaginal hysterectomy. CONCLUSION: Surgery for pelvic organ prolapse is
common and more than every tenth woman underwent such surgery during lifetime.
PMID- 28494264
TI - High yield, scalable and remotely drug-loaded neutrophil-derived extracellular
vesicles (EVs) for anti-inflammation therapy.
AB - Extracellular vesicles (EVs) are nanoscale membrane-formed compartments naturally
secreted from cells, which are intercellular mediators regulating physiology and
pathogenesis, therefore they could be a novel therapeutic carrier for targeted
delivery. However, the translation of EVs is hindered by the heterogeneous
composition, low yield, inefficient drug loading and unlikely scalability. Here
we report a strategy to generate EVs using nitrogen cavitation (NC-EVs) that
instantly disrupts neutrophils to form nanosized membrane vesicles. NC-EVs are
similar to naturally secreted EVs (NS-EVs), but contain less subcellular
organelles and nuclear acids. The production of NC-EVs was increased by 16 folds
and is easy to scale up for clinical use compared to NS-EVs. To examine the
usefulness of NC-EVs as a drug delivery platform, piceatannol (an anti
inflammation drug) was remotely loaded in NC-EVs via the pH gradient. We found
that piceatannol-loaded NC-EVs dramatically alleviated acute lung
inflammation/injury and sepsis induced by lipopolysaccharide (LPS). Our studies
reveal that nitrogen cavitation is a novel approach to efficiently generate EVs
from any cell type and could be exploited for personalized nanomedicine.
PMID- 28494267
TI - Advanced glycation products' levels and mechanical properties of vaginal tissue
in pregnancy.
AB - OBJECTIVES: Non-enzymatic glycation is closely associated with altered mechanical
properties of connective tissue. Pregnancy, marked with high levels of female
hormones, confers unique alteration to the mechanical properties of pelvic
connective tissues in order to meet their physiological demands. However, there
are few studies on glycation content and its influence on the mechanical
properties of pelvic connective tissues during pregnancy. We hypothesise that the
glycation content in pelvic tissues will change with a corresponding alteration
in their mechanical properties, and that these changes are influenced by hormone
levels. This study aims to investigate the correlation of vaginal tissue
glycation content and mechanical property changes during pregnancy in association
with the expression of a key pregnancy hormone (oestrogen) receptor, and an
antioxidant enzyme, glyoxalase I. STUDY DESIGN: A rat vaginal tissue model
(tissues from non-pregnant and E15-E18 (last trimester) pregnant rats) was used
in this study. Mechanical characteristics of vaginal tissues were analysed by a
ball-indentation technique while modulus and morphology of the collagen fibrils
within the tissues were measured with atomic force microscopy. A glycation
marker, pentosidine, was quantified by a high performance liquid chromatography.
The expression of oestrogen receptor and glyoxalase I in the tissue was qualified
by immunochemical staining. The glycosaminoglycan (GAG) concentration difference
in the tissues were quantified by a biochemical assay. RESULTS: Pregnant rat
vaginal tissue was characterised by significantly lower amounts of pentosidine,
higher oestrogen receptor and glyoxalase I expression with larger creep, lower
elastic modulus, larger fibril diameter and higher GAG content than their non
pregnant counterpart. There was a negative correlation between pentosidine and
vaginal tissue creep. CONCLUSION: There was a reduction in vaginal tissue
pentosidine in pregnancy with an associated increase in oestrogen receptor and
glyoxalase I immunoexpression. Reduced glycation was associated with increased
creeping of vaginal tissue. Oestrogen may therefore play a role in the increase
of the vaginal wall's capacity to stretch through glyoxalase I up-regulation and
subsequent glycation reduction. The new insight of the correlation of women's
oestrogen level, glycation reaction and pelvic tissue mechanical property from
this study may enhance our understanding of some pelvic organ diseases.
PMID- 28494268
TI - Pregnancy outcome and cord blood cotinine level: A cross-sectional comparative
study between secondhand smokers and non-secondhand smokers.
AB - OBJECTIVE: To compare the pregnancy outcome and cord blood cotinine levels
between secondhand smokers and non-secondhand smokers. STUDY DESIGN: This was a
cross-sectional comparative study in a Malaysian tertiary obstetric hospital
involving 200 non-smoking pregnant women at term, of whom 100 were secondhand
smokers and 100 were non-secondhand smokers. Those with multiple pregnancies,
with a body mass index (BMI) of more than 30kg/m2 or who delivered by Caesarean
section were excluded. The participants' basic demographic details, delivery
details, neonatal outcome and placental weight were recorded. Umbilical cord
blood samples were obtained, and cord blood cotinine levels were measured with a
Cotinine ELISA kit. The primary outcomes were baby's birth weight, length, and
head circumference, Apgar score at 5min and placental weight. The secondary
outcome was difference in cord blood cotinine levels between the two groups and
the correlation of these differences with the neonatal outcome. RESULTS: The
secondhand smoker group had significantly lower baby weight (2.94+/-0.31kg vs
3.05+/-0.40kg), head circumference (30.87+/-2.35cm vs 37.13+/-2.36cm), length
(46.58+/-1.95cm vs 51.53+/-2.05cm) and placental weight (520+/-73.5g vs 596+/
61.3g) and significantly higher cord blood cotinine levels (16.35+/-12.84ng/mL vs
0.56+/-0.22ng/mL). Cord blood cotinine levels had significant negative
correlations with placental weight (r=-0.461), baby's weight (r=-0.297), baby's
head circumference (r=-0.501) and baby's length (r=-0.374). CONCLUSION:
Secondhand smoke increases the incidence of adverse pregnancy outcomes
(newborns'anthropometric measurements and placental weight) and causes higher
cord blood cotinine levels.
PMID- 28494269
TI - Medical conditions associated with recurrent miscarriage-Is BMI the tip of the
iceberg?
AB - BACKGROUND: In contrast to sporadic miscarriage, recurrent miscarriage (RM) is a
rare entity which affects 1% of couples attempting conception. It is distressing
for couples and healthcare professionals as the aetiology is unclear with limited
treatment options. Apart from anti-phospholipid syndrome (APS), the strength of
associations between RM and commonly investigated endocrine, autoimmune,
thrombophilic and uterine structural abnormalities remains uncertain and
variable. OBJECTIVES: To assess the prevalence of commonly investigated medical
conditions associated with RM. STUDY DESIGN: A 9-year retrospective analysis of a
prospectively collected database was conducted for 592 patients seen between 2008
and 2016, in tertiary level RM clinic in South Africa. RESULTS: In this period,
592 patients were assessed. The mean age was 29.73+/-5.46 (mean+/-SD), gravidity
4.6+/-1.82 and parity 0.98+/-1.05. The mean number of miscarriages per patient
was 3.34+/-1.63, of which two-thirds (61.3%) were in the first trimester, a third
(33%) in the second trimester and intrauterine fetal deaths (IUFDs) constituted
6% of total losses. Of the 50% of patients with no identified associated
disorders, 15% were unexplained (investigations complete but no associations
found), 10% became pregnant during investigation (investigations incomplete) and
25% were lost to follow-up (investigations incomplete). Nearly forty percent
(38%) of patients had an associated endocrine disorder (22% PCOS, 11% IGT, 3%
Diabetes Mellitus and 2% Thyroid Dysfunction) and 10% a uterine factor (4%
Cervical Incompetence, 2% Fibroids, 2% Synechiae and 2% Anomalies). APS and
Thrombophilias constituted 3% and 2% of patients respectively. The BMI (mean+/
SD) amongst patients with Unexplained RM, PCOS and IGT were 28.85+/-5.95, 30.86+/
7.79 and 33.40+/-6.47 respectively. Patients with IGT had significantly higher
mean BMI in comparison to those with Unexplained RM (p<0.0001)*** and PCOS
(p<0.001)**. CONCLUSION: PCOS, IGT and Type II Diabetes are all likely surrogates
for elevated BMI and constitute 70% of those women with RM and identified
associated medical disorders. In our population, BMI seems to have a substantial
impact on recurrent pregnancy loss and future studies should interrogate its
effect on recurrent miscarriage.
PMID- 28494270
TI - Vaginal wind: A literature review.
AB - OBJECTIVE: In the medical literature, there is little known about vaginal wind,
though from clinical expertise, it turns out to be a consistent and underreported
problem. The aim of this review was to collect the available literature about the
different aspects of vaginal wind. STUDY DESIGN: A systematic literature search
was conducted using three databases until December 2015. The search strategy was
built using relevant synonyms of vaginal wind. Study characteristics were
extracted. Risk of bias, the quality of the relevant studies and the level of
evidence was judged. RESULTS: Eleven studies met the inclusion criteria. Vaginal
wind occurs on random movements and during or after coitus. The prevalence ranges
from one to 69%. The pathophysiology is unclear and the incidence unknown. Known
risk factors are vaginal delivery and urinary incontinence. Provoking factors are
coitus, digital stimulation, cunnilingus and exercising. Female sexual function
is decreased. The sexual function of male partners with vaginal wind is not
influenced. Overall vaginal wind leads to a decrease in the quality of live and
can have cause social isolation. The treatment is related to the cause and mainly
not successful. Tampons can be used for treatment as well as prevention.
CONCLUSION: Vaginal wind is an underestimated health issue with a severe impact
on sexual functioning. Adequate research is needed regarding the influence of
sexual activity, weight, age, parity, the underlying pathophysiological
mechanisms, prevention and treatment.
PMID- 28494271
TI - Motion-robust parameter estimation in abdominal diffusion-weighted MRI by
simultaneous image registration and model estimation.
AB - Quantitative body DW-MRI can detect abdominal abnormalities as well as monitor
response-to-therapy for applications including cancer and inflammatory bowel
disease with increased accuracy. Parameter estimates are obtained by fitting a
forward model of DW-MRI signal decay to the observed data acquired with several b
values. The DW-MRI signal decay models typically used do not account for
respiratory, cardiac and peristaltic motion, however, which may deteriorate the
accuracy and robustness of parameter estimates. In this work, we introduce a new
model of DW-MRI signal decay that explicitly accounts for motion. Specifically,
we estimated motion-compensated model parameters by simultaneously solving image
registration and model estimation (SIR-ME) problems utilizing the interdependence
of acquired volumes along the diffusion-weighting dimension. To accomplish this,
we applied the SIR-ME model to the in-vivo DW-MRI data sets of 26 Crohn's disease
(CD) patients and achieved improved precision of the estimated parameters by
reducing the coefficient of variation by 8%, 24% and 8% for slow diffusion (D),
fast diffusion (D*) and fast diffusion fraction (f) parameters respectively,
compared to parameters estimated with independent registration in normal
appearing bowel regions. Moreover, the parameters estimated with the SIR-ME model
reduced the error rate in classifying normal and abnormal bowel loops to 12% for
D and 10% for f parameter with a reduction in error rate by 13% and 11% for D and
f parameters, respectively, compared to the error rate in classifying parameter
estimates obtained with independent registration. The experiments in DW-MRI of
liver in 20 subjects also showed that the SIR-ME model improved the precision of
parameter estimation by reducing the coefficient of variation to 7% for D, 23%
for D*, and 8% for the f parameter. Using the SIR-ME model, the coefficient of
variation was reduced by 4%, 14% and 6% for D, D* and f parameters, respectively,
compared to parameters estimated with independent registration. These results
demonstrate that the proposed SIR-ME model improves the accuracy and robustness
of quantitative body DW-MRI in characterizing tissue microstructure.
PMID- 28494272
TI - A new inverse method for estimation of in vivo mechanical properties of the
aortic wall.
AB - The aortic wall is always loaded in vivo, which makes it challenging to estimate
the material parameters of its nonlinear, anisotropic constitutive equation from
in vivo image data. Previous approaches largely relied on either computationally
expensive finite element models or simplifications of the geometry or material
models. In this study, we investigated a new inverse method based on aortic wall
stress computation. This approach consists of the following two steps: (1)
computing an "almost true" stress field from the in vivo geometries and loading
conditions, (2) building an objective function based on the "almost true" stress
fields, constitutive equations and deformation relations, and estimating the
material parameters by minimizing the objective function. The method was
validated through numerical experiments by using the in vivo data from four
ascending aortic aneurysm (AsAA) patients. The results demonstrated that the
method is computationally efficient. This novel approach may facilitate the
personalized biomechanical analysis of aortic tissues in clinical applications,
such as in the rupture risk analysis of ascending aortic aneurysms.
PMID- 28494274
TI - Personalized T cell-mediated cancer immunotherapy: progress and challenges.
AB - Immunotherapies are yielding effective treatments for several previously
untreatable cancers. Until recently, vaccines and adoptive cell therapies have
been designed to target public tumor antigens common to multiple patients rather
than private antigens specific to a single patient. Due to the difficulty of
identifying public antigens that are expressed exclusively on tumor cells, these
studies have yielded both clinical successes and serious immune-related adverse
events. Multiple avenues of research now underscore the centrality of tumor
specific mutated private antigens to endogenous anti-tumor immunity.
Immunotherapies that target these neoantigens may enable safer and more durable
tumor regression, but personalized targeting presents a number of challenges.
Foremost among these is to develop processes that accelerate advancement from
neoantigen discovery to use of these neoantigens as vaccines or as targets for
adoptive cell therapies. Exome sequencing has facilitated discovery of
neoantigens for melanoma and other highly mutated cancers. New technologies -
possibly proceeding from T cell receptor repertoire sequencing - are needed to
identify antigens for cancers with low mutational burden and few neoantigens. In
this review, we discuss progress toward personalizing T cell-mediated
immunotherapy for cancer as well as challenges going forward.
PMID- 28494273
TI - Fatigue limit of monolithic Y-TZP three-unit-fixed dental prostheses: Effect of
grinding at the gingival zone of the connector.
AB - OBJECTIVES: To determine the fatigue limits of three-unit monolithic zirconia
fixed dental prosthesis (FDPs) before and after grinding of the gingival areas of
connectors with diamond burs. MATERIAL AND METHODS: FDPs were milled from pre
sintered blocks of zirconia simulating the absence of the first mandibular molar.
Half of the specimens were subjected to grinding, simulating clinical adjustment,
and all of them were subjected to glazing procedure. Additional specimens were
manufactured for roughness analysis. FDPs were adhesively cemented onto glass
fiber reinforced epoxy resin abutments. Fatigue limits and standard deviations
were obtained using a staircase fatigue method (n=20, 100,000 loading
cycles/5Hz). The initial test load was 70% of the mean load-to-fracture (n=3) and
load increments were 5% of the initial test load for both the control and ground
specimens. Data were compared by Student's T-test (alpha<=0.05). RESULTS: Both
the control and ground groups exhibited similar values of load-to-fracture and
fatigue limits. Neither the surface treatments nor ageing affected the surface
roughness of the specimens. CONCLUSIONS: The damage induced by grinding with fine
grit diamond bur in the gingival area of the connectors did not decrease the
fatigue limit of the three-unit monolithic zirconia FDP.
PMID- 28494275
TI - Synthetic biological approaches for RNA labelling and imaging: design principles
and future opportunities.
AB - RNA is the most mercurial of all biomacromolecules. In contrast to DNA, where the
predominant role is the storage of genetic information, the biological role of
RNA varies; ranging from a template-based intermediary in gene expression to
playing a direct role in catalysis. Their high turnover and metabolic lability
makes the detection of specific sequences particularly challenging. This review
describes the latest synthetic biological developments that enable the direct
imaging of RNA both in vitro and in their native cellular environment.
PMID- 28494276
TI - Prediction of ligand effects in platinum-amyloid-beta coordination.
AB - Ligand field molecular mechanics (LFMM) and semi-empirical Parametric Model 7
(PM7) methods are applied to a series of six PtII-Ligand systems binding to the N
terminal domain of the amyloid-beta (Abeta) peptide. Molecular dynamics using a
combined LFMM/Assisted Model Building with Energy Refinement (AMBER) approach is
used to explore the conformational freedom of the peptide fragment, and
identifies favourable platinum binding modes and peptide conformations for each
ligand investigated. Platinum coordination is found to depend on the nature of
the ligand, providing evidence that binding mode may be controlled by suitable
ligand design. Boltzmann populations at 310K indicate that each Pt-Abeta complex
has a small number of thermodynamically accessible states. Ramachandran maps are
constructed for the sampled Pt-Abeta conformations and secondary structural
analysis of the obtained complex structures is performed and contrasted with the
free peptide; coordination of these platinum complexes disrupts existing
secondary structure in the Abeta peptide and promotes formation of ligand
specific turn-type secondary structure.
PMID- 28494277
TI - Toxicity of Quaternary Ammonium Compounds (QACs) as single compounds and mixtures
to aquatic non-target microorganisms: Experimental data and predictive models.
AB - The toxic effects of five Quaternary Ammonium Compounds (QACs) that are widely
used as active ingredients in personal care products were assessed using the
bioluminescent bacterium Aliivibrio fischeri (formerly Vibrio fischeri)
(Microtox(r) test system). The experimental results showed a relevant toxicity
for almost all of the single QACs, with IC50 values lower than 1mgL-1. Analysis
of the mode of action through the application of the Quantitative Structure
Activity Relationship (QSAR) models indicated an a-specific reactivity for most
of the QACs toward A. fischeri. Only hexadecyl trimethyl ammonium chloride (ATMAC
16) behaved as a polar-narcotic, with a low reactivity toward the bacterial cell
membrane. The concentration response curves of the different binary and
multicomponent mixtures of QACs were also evaluated with respect to the
predictions from the Concentration Addition (CA) and Independent Action (IA)
models. For almost all of the binary and multicomponent mixtures (7 out of 11
mixtures tested), an agreement between the experimental and predicted ICx was
observed and confirmed via application of the Model Deviation Ratio (MDR). In
four cases, some deviations from the expected behaviour were observed (potential
antagonistic and synergistic interactions) at concentrations on the order of
hundreds of ugL-1, which could be of environmental concern, especially in the
case of synergistic effects. The analysis of aquatic ecotoxicity data and the few
available values of the measured environmental concentrations (MECs) from the
literature for wastewaters and receiving waterbodies suggest that a potential
risk toward aquatic life cannot be excluded.
PMID- 28494278
TI - Outcomes of ultrasound-guided axillary lymph node sampling in the absence of
primary breast cancer.
AB - PURPOSE: To evaluate outcomes of lymph node sampling in patients with suspicious
axillary nodes without a diagnosis of breast cancer. MATERIALS AND METHODS: We
retrospectively identified all axillary ultrasound-guided sampling performed at
our institution from 2003 to 2016 in patients. without malignancy. RESULTS:
Seventy-eight lymph nodes met inclusion criteria. Two of the 78 sampled nodes
(2.6%) were malignant. CONCLUSION: Sampling of suspicious nodes in patients
without a history of breast cancer rarely yields malignancy. The malignancy rate
approaches the 2% BIRADS 3 threshold. Further data may demonstrate that short
interval imaging follow-up is a safe alternative to sampling in this cohort.
PMID- 28494279
TI - Gastrointestinal stromal tumor presenting as a right adnexal mass with
histopathologic correlation.
AB - The authors report and discuss a rare case of a gastrointestinal stromal tumor
(GIST) in a 35-year-old female, which was pre-procedurally characterized as a
right ovarian mass by magnetic resonance imaging (MRI) features. This manuscript
reviews the imaging and clinical features of GISTs with pathologic correlation,
and emphasizes how this entity may present a diagnostic challenge in certain
anatomic regions owing in large part to its exophytic nature. This case is unique
among similarly reported cases in that there was a "claw sign" with the right
ovary, which provided convincing evidence of its point of origin.
PMID- 28494280
TI - Iron mineralogy as a fingerprint of former steelmaking activities in river
sediments.
AB - Submerged sediment cores were collected upstream of a dam in the Orne River,
northeastern France. This dam was built in the context of steelmaking to
constitute a water reservoir for blast furnace cooling and wet cleaning of
furnace smokes. The dam also enhanced sediment deposition in the upstream zone.
This study was performed to unravel the contamination status of sediments and to
evidence possible contribution sources. The sediment layers were analyzed for
water content, grain size, chemical composition, crystalline phases at a bulk
scale and poorly crystalline and amorphous phases at a sub-micrometer scale.
Visual aspect, texture, color, and chemical and mineralogical analyses showed
that the settled sediments were mainly composed of fine black matter, certainly
comprising steelmaking by-products. Those materials were highly enriched with Fe,
Zn, Pb and other trace metals, except for a relatively thin layer of surficial
sediments that had settled more recently. Bulk mineralogy revealed crystalline
iron minerals, such as magnetite, goethite, wuestite and pyrite, in the deep
layers of the sediment cores. Furthermore, microscopic investigations evidenced
the presence of ferrospheres, goethite nanoparticles and newly formed Fe
aluminosilicates; all originating from the former steelmaking facilities. The
variation of iron mineralogy, combined with specific chemical profiles and other
sediment features, demonstrate the different contributions that constitute the
sediment deposit. Furthermore, chemical and mineralogical features of goethite
and Fe-aluminosilicates could be used as a fingerprint for such contaminated
sediments.
PMID- 28494281
TI - Using deltaDn-alkane as a proxy for paleo-environmental reconstruction: A good
choice to sample at the site dominated by woods.
AB - Some studies have demonstrated that leaf wax deltaDn-alkane values for a single
species varied significantly with seasons. However, it is still not clear that
the seasonality patterns of leaf wax deltaDn-alkane values in higher plants.
Meanwhile, few efforts have been pursued to assess the effect of the light slopes
(sunny vs. cloudy) on leaf wax deltaDn-alkane values. In this study, we
systematically investigated plant wax deltaDn-alkane values and soil n-alkane
deltaD values along different light slopes in different seasons (spring vs.
autumn), as well as the relationship of n-alkane deltaD values between plant
leaves and soil. We found that plant wax deltaDn-alkane values were D-enriched by
ca. 200/00 in spring relative to autumn, and ca. 100/00 in the sunny slope than
in the cloudy slope. Moreover, surface soil n-alkane deltaD values varied
consistently with plant wax deltaDn-alkane values for different seasons and light
slopes. More importantly, plant wax deltaDn-alkane values showed clear seasonal
variations, but varied slightly with light slopes. The variations of plant wax
deltaDn-alkane values can be recorded in soil n-alkane deltaDn-alkane values. In
addition, we found that leaf wax deltaDn-alkane values in a majority of species
differed significantly among woods, non-woods and grasses at a site. Therefore,
we suggested a good choice to sample at the site dominated by woods when leaf wax
deltaDn-alkane values are utilized as a proxy for the reconstruction of the
paleoenvironment.
PMID- 28494282
TI - Anthropogenic fibres in the Baltic Sea water column: Field data, laboratory and
numerical testing of their motion.
AB - Distribution of microplastics particles (MPs) in the water column is investigated
on the base of 95 water samples collected from various depths in the Baltic Sea
Proper in 2015-2016. Fibres are the prevalent type of MPs: 7% of the samples
contained small films; about 40% had (presumably) paint flakes, while 63%
contained coloured fibres in concentrations from 0.07 to 2.6 items per litre.
Near-surface and near-bottom layers (defined as one tenth of the local depth)
have 3-5 times larger fibre concentrations than intermediate layers. Laboratory
tests demonstrated that sinking behaviour of a small and flexible fibre can be
complicated, with 4-fold difference in sinking velocity for various random
fibres' curvature during its free fall. Numerical tests on transport of fibres in
the Baltic Sea Proper were performed using HIROMB reanalysis data (2007) for the
horizontal velocity field and laboratory order-of-magnitude estimates for the
sinking velocity of fibres. The model takes into account (i) motion of fibres
together with currents, (ii) their very slow sinking, and (iii) their low re
suspension threshold. Sensitivity of the final distribution of fibres to
variations of those parameters is examined. These experiments are the first step
towards modelling of transport of fibres in marine environment and they seem to
reproduce the main features of fibres distribution quite well.
PMID- 28494283
TI - Preliminary study of phytoremediation of brownfield soil contaminated by PAHs.
AB - Our project was aimed at improving a brownfield in the city of Kladno, where an
old steel producing facility used to be in operation. Ecological risk is mainly
caused by the processing of co-products during coal production (tars, oils).
Knowledge of toxicology and environmental aspects can help us protect human
health and the environment. Primarily, we focused on soil sampling and
identification of pollutants. Results showed that organic contamination on the
site is very high. Average concentration of total petroleum carbon in the soil
was about 13g/kg DW, which is much more than the maximum allowed concentration.
For selection of suitable plant species for phytoremediation at the site,
experiments were conducted in a greenhouse. Biomass growth, root morphology, and
pigment content in the leaves of Brassica napus var. Opus-C1 and
Sorghum*drummondii var. Honey Graze BMR plants were studied. Plant analysis
confirmed that polyaromatic hydrocarbons (PAHs) accumulated in the shoots of both
plant species. B. napus plants grown on Poldi soil in a greenhouse were able to
survive the toxicity of PAHs in soil, and their ability to accumulate PAHs from
soil was evident. However, more studies are needed to decide if the plants are
usable for phytoremediation of this brownfield.
PMID- 28494284
TI - Evaluating the impact of irrigation on surface water - groundwater interaction
and stream temperature in an agricultural watershed.
AB - Changes in groundwater discharge to streams caused by irrigation practices can
influence stream temperature. Observations along two currently flood-irrigated
reaches in the 640-square-kilometer upper Smith River watershed, an important
agricultural and recreational fishing area in west-central Montana, showed a
downstream temperature decrease resulting from groundwater discharge to the
stream. A watershed-scale coupled surface water and groundwater flow model was
used to examine changes in streamflow, groundwater discharge to the stream and
stream temperature resulting from irrigation practices. The upper Smith River
watershed was used to develop the model framework including watershed climate,
topography, hydrography, vegetation, soil properties and current irrigation
practices. Model results were used to compare watershed streamflow, groundwater
recharge, and groundwater discharge to the stream for three scenarios: natural,
pre-irrigation conditions (PreIrr); current irrigation practices involving mainly
stream diversion for flood and sprinkler irrigation (IrrCurrent); and a
hypothetical scenario with only groundwater supplying sprinkler irrigation
(IrrGW). Irrigation increased groundwater recharge relative to natural PreIrr
conditions because not all applied water was removed by crop evapotranspiration.
Groundwater storage and groundwater discharge to the stream increased relative to
natural PreIrr conditions when the source of irrigation water was mainly stream
diversion as in the IrrCurrent scenario. The hypothetical IrrGW scenario, in
which groundwater withdrawals were the sole source of irrigation water, resulted
in widespread lowering of the water table and associated decreases in groundwater
storage and groundwater discharge to the stream. A mixing analysis using model
predicted groundwater discharge along the reaches suggests that stream diversion
and flood irrigation, represented in the IrrCurrent scenario, has led to cooling
of stream temperatures relative to natural PreIrr conditions improving fish
thermal habitat. However, the decrease in groundwater discharge in the IrrGW
scenario resulting from large-scale groundwater withdrawal for irrigation led to
warmer than natural stream temperatures and possible degradation of fish habitat.
PMID- 28494285
TI - Effects of in situ exposure to tritiated natural environments: A multi-biomarker
approach using the fathead minnow, Pimephales promelas.
AB - Aquatic ecosystems are chronically exposed to radionuclides as well as other
pollutants. Increased concentrations of pollutants in aquatic environments can
present a risk to exposed organisms, including fish. The goal of this study was
to characterize the effects of tritium, in the context of natural environments,
on the health of fathead minnow, Pimephales promelas. Fish were exposed to
tritium (activity concentrations ranging from 2 to 23,000Bq/L) and also to
various concentrations of several metals to replicate multiple-stressor
environments. Fish were exposed for 60days, then transferred to the tritium
background site where they stayed for another 60days. Tritium, in the forms of
tritiated water (HTO) and organically bound tritium (OBT), and a series of fish
health indicators were measured in fish tissues at seven time points throughout
the 120days required to complete the exposure and the depuration phases. Results
showed effects of environmental exposure following the increase of tritium
activity and metals concentrations in water. The internal dose rates of tritium,
estimated from tissue HTO and OBT activity concentrations, were consistently low
(maximum of 0.2MUGy/h) compared to levels at which population effects may be
expected (>100MUGy/h) and no effects were observed on survival, fish condition,
gonado-somatic, hepato-somatic, spleno-somatic and metabolic indices (RNA/DNA,
proteins/DNA and protein carbonylation (in gonads and kidneys)). Using
multivariate analyses, we showed that several biomarkers (DNA damages, MN
frequency, gamma-H2AX, SFA/MUFA ratios, lysosomal membrane integrity, AChE, SOD,
phagocytosis and esterase activities) were exclusively correlated with fish
tritium internal dose rate, showing that tritium induced genotoxicity, DNA repair
activity, changes in fatty acid composition, and immune, neural and antioxidant
responses. Some biomarkers were responding to the presence of metals, but
overall, more biomarkers were linked to internalized tritium. The results are
discussed in the context of multiple stressors involving metals and tritium.
PMID- 28494286
TI - Slurry photocatalytic membrane reactor technology for removal of pharmaceutical
compounds from wastewater: Towards cytostatic drug elimination.
AB - The potential of photocatalytic membrane reactors (PMR) to degrade cytostatic
drugs is presented in this work as an emerging technology for wastewater
treatment. Cytostatic drugs are pharmaceutical compounds (PhCs) commonly used in
cancer treatment. Such compounds and their metabolites, as well as their degraded
by-products have genotoxic and mutagenic effects. A major challenge of cytostatic
removal stands in the fact that most drugs are delivered to ambulant patients
leading to diluted concentration in the municipal waste. Therefore safe
strategies should be developed in order to collect and degrade the micro
pollutants using appropriate treatment technologies. Degradation of cytostatic
compounds can be achieved with different conventional processes such as chemical
oxidation, photolysis or photocatalysis but the treatment performances obtained
are lower than the ones observed with slurry PMRs. Therefore the reasons why
slurry PMRs may be considered as the next generation technology will be discussed
in this work together with the limitations related to the mechanical abrasion of
polymeric and ceramic membranes, catalyst suspension and interferences with the
water matrix. Furthermore key recommendations are presented in order to develop a
renewable energy powered water treatment based on long lifetime materials.
PMID- 28494287
TI - 137Cs contamination over Transylvania region (Romania) after Chernobyl Nuclear
Power Plant Accident.
AB - Following the radionuclide releases due to Chernobyl Nuclear Power Plant
accident, various studies were completed by researchers all over the world in
order to measure the surface contaminations by artificial radionuclides. The aim
of this study was to evaluate 137Cs surface contamination and to create an
inventory distribution for Transylvania region (Romania) after the Chernobyl
event using gamma spectrometric measurements on soil samples collected from 153
locations. The results were compared to measured data from the Danube Delta and
Moldova Republic, as well as to 137Cs concentrations from the rest of Europe
reported by literature. The 137Cs surface concentrations in soil samples ranged
between 0.4+/-0.1kBqm-2 and 301.1+/-3.0kBqm-2, having an average of 8.3+/-0.2kBqm
2, with more elevated values in the mountain areas (18.3+/-0.6kBqm-2) compared to
the hills and plains (2.6+/-0.1kBqm-2). Taking into consideration the cardinal
regions, the northern and western regions received the least amount of 137Cs
(2.9+/-0.1kBqm-2), while the southern part received 16.3+/-0.6kBqm-2. Sampling
points with eastern slope exposure received the highest average (27.8+/-0.5kBqm
2), while southern, north-western and north-eastern ones received less than 8kBqm
2. Two hotspots are reported at Iezer-Ighiel (72.7+/-5.9kBqm-2) and Tulghes areas
(51.5+/-0.6kBqm-2).
PMID- 28494288
TI - Growth trends of beech and Norway spruce in Switzerland: The role of nitrogen
deposition, ozone, mineral nutrition and climate.
AB - Understanding the effects of nitrogen deposition, ozone and climate on tree
growth is important for planning sustainable forest management also in the
future. The complex interplay of all these factors cannot be covered by
experiments. Here we use observational data of mature forests for studying
associations of various biotic and abiotic factors with tree growth. A 30year
time series on basal area increment of Fagus sylvatica L. and Picea abies Karst.
in Switzerland was analyzed to evaluate the development in relation to a variety
of predictors. Basal area increment of Fagus sylvatica has clearly decreased
during the observation period. For Picea abies no trend was observed. N
deposition of more than 26 (beech) or 20-22kgNha-1year-1 (Norway spruce) was
negatively related with basal area increment, in beech stronger than in Norway
spruce. High N deposition loads and low foliar K concentrations in Fagus were
correlated with increased drought sensitivity. High air temperatures in winter
were negatively related with basal area increment in Norway spruce in general and
in beech at high N:Mg ratio or high N deposition while on an average the relation
was positive in beech. Fructification in beech was negatively related to basal
area increment. The increase of fructification observed during the last decades
contributed thus to the growth decrease. Ozone flux was significantly and
negatively correlated with basal area increment both in beech and Norway spruce.
The results show clear non-linear effects of N deposition on stem increment of
European beech and Norway spruce as well as strong interactions with climate
which have contributed to the growth decrease in beech and may get more important
in future. The results not only give suggestions for ecological processes but
also show the potential of an integral evaluation of observational data.
PMID- 28494289
TI - Observational evidence of a long-term increase in precipitation due to
urbanization effects and its implications for sustainable urban living.
AB - Although projected precipitation increases in East Asia due to future climate
change have aroused concern, less attention has been paid by the scientific
community and public to the potential long-term increase in precipitation due to
rapid urbanization. A ten-year precipitation dataset was analysed for both a
rapidly urbanized megacity and nearby suburban/rural stations in southern China.
Rapid urbanization in the megacity was evident from satellite observations. A
statistically significant, long-term, increasing trend of precipitation existed
only at the megacity station (45.6mm per decade) and not at the other stations.
The increase was attributed to thermal and dynamical modifications of the
tropospheric boundary layer related to urbanization, which was confirmed by the
results of our WRF-SLUCM simulations. The results also suggested that a long-term
regional increase in precipitation, caused by greenhouse gas-induced climate
change, for instance, was not evident within the study period. The urbanization
induced increase was found to be higher than the precipitation increase (18.3mm
per decade) expected from future climate change. The direct climate impacts due
to rapid urbanization is highlighted with strong implications for urban
sustainable development and the planning of effective adaptation strategies for
issues such as coastal defenses, mosquito-borne disease spread and heat stress
mortality.
PMID- 28494290
TI - Importance of aerosol non-sphericity in estimating aerosol radiative forcing in
Indo-Gangetic Basin.
AB - Aerosols are usually presumed spherical in shape while estimating the direct
radiative forcing (DRF) using observations or in the models. In the Indo-Gangetic
Basin (IGB), a regional aerosol hotspot where dust is a major aerosol species and
has been observed to be non-spherical in shape, it is important to test the
validity of this assumption. We address this issue using measured chemical
composition at megacity Delhi, a representative site of the western IGB. Based on
the observation, we choose three non-spherical shapes - spheroid, cylinder and
chebyshev, and compute their optical properties. Non-spherical dust enhances
aerosol extinction coefficient (betaext) and single scattering albedo (SSA) at
visible wavelengths by >0.05km-1 and >0.04 respectively, while it decreases
asymmetry parameter (g) by ~0.1. Accounting non-sphericity leads top-of-the
atmosphere (TOA) dust DRF to more cooling due to enhanced backscattering and
increases surface dimming due to enhanced betaext. Outgoing shortwave flux at TOA
increases by up to 3.3% for composite aerosols with non-spherical dust externally
mixed with other spherical species. Our results show that while non-sphericity
needs to be accounted for, choice of shape may not be important in estimating
aerosol DRF in the IGB.
PMID- 28494291
TI - Distribution and sensorial relevance of volatile organic compounds emitted
throughout wastewater biosolids processing.
AB - A diverse range of volatile organic compounds (VOCs) are emitted from wastewater
biosolids processing. Odorous emissions are predominately made up of volatile
sulfur compounds (VSCs) which are typically the only odorants measured. However,
a range of VOCs are known to contribute to malodours yet previous studies often
overlook the contribution of VOCs in comparison with VSCs. This study aims to
evaluate how emissions are affected by different biosolids processing
configurations, and if any non-sulfur VOCs should be included in odour
measurement and management. Non-sulfur VOCs emitted from biosolids throughout six
wastewater treatment plants in the Sydney, Australia region were measured at six
locations on average twice each week over 2-3weeks at each site. Variations in
types of VOCs emitted throughout and between the sites were assigned to
differences in WWTP processing configurations, plant operation and variations in
industrial and municipal flows to the sewer network, referred to as sewer
catchments. The presence of VOCs is likely due to biotic generation as well as
industrial or residential additions to the sewer network. The dewatered and
stored biosolids samples had the highest levels of VOC emissions. Sensorially
important odorants were p-cresol and butanoic acid, based on the frequency of
detection and odour activity values. Other compounds with a high risk of nuisance
impacts were trimethylamine, indole and phenol emitted from the dewatered and
stored biosolids, and volatile fatty acids from the anaerobic digester inlet and
outlet at one particular site. The findings show that non-sulfur VOCs should be
added to odorant monitoring campaigns at WWTPs. Identification of VOCs as
sensorially important odorants opens opportunities for the more efficient
management of nuisance odours, through targeted odour control or process
improvement.
PMID- 28494292
TI - Trace element levels in an area impacted by old mining operations and their
relationship with beehive products.
AB - The environmental status of an area impacted by Roman mining activities was
assessed in order to establish the current risks posed by such old mine
emplacements. For this purpose, soil samples were collected throughout the mining
area and analysed for their total, mobile and mobilizable trace element (As, Cd,
Mo, Sb and Zn) contents. Additionally, beehive products (honey and pollen) were
also sampled and evaluated for their use as environmental indicators of the area.
The results obtained were compared with those from a control non-polluted area.
The mine soils presented slightly increased levels of Cd and Sb (about 2- to -3
fold their normal soil concentrations), whereas the enrichment of As reached
considerable levels, with concentrations almost ten-fold of those considered the
threshold for causing toxicity. Leachable As contents exhibited very high values
(1.2-21.9mgkg-1), indicating the need for risk attenuation measures. All trace
elements were mainly partitioned in the soil residual fraction, especially Mo (76
99%) and Sb (61-91%). Significant partitioning levels were also found in the
reducible fraction of As (up to 35%) and Cd (up to 38%), and in the oxidizable
fraction of Mo (up to 23%). The reducible pool of As was particularly relevant
due to the eventual mobilization of this element under reducing conditions. Among
the beehive products tested, honey proved not to be useful as an environmental
indicator, whereas pollen showed great potential as an indicator when the
contamination levels were moderate to high.
PMID- 28494293
TI - Fate of arsenic before and after chemical-enhanced washing of an arsenic
containing soil in Hong Kong.
AB - This study evaluated the feasibility of 2-h chemical-enhanced washing of As
containing soil resulting from geogenic sources in Hong Kong and the fate of As
before and after remediation. The soil morphology and As speciation in soil was
elucidated by scanning electron microscopy with energy dispersive X-ray
spectroscopy, X-ray diffractometer, X-ray photoelectron spectroscopy, and X-ray
absorption spectroscopy. Integrated analysis of the results suggests that the As
(>90%) resides predominantly as arsenate bound to ferric iron oxides, with a
minor contribution (<10%) from an AsIII-sulphide phase. This accounts for the
marginal leachability, mobility, and bioaccessibility of geogenic As in the
untreated soil despite its high concentration. Among the five types of reagents
(organic ligands, reductants, alkaline solvents, inorganic acids, and chelants),
only dithionite-citrate-bicarbonate method and alkaline solvents (NaOH and
Na2CO3) extracted 37-78% and 26-42% of the As by mineral dissolution. However,
these extraction methods notably increased the leachability, mobility, and
bioaccessibility of remaining As after soil washing, suggesting that a
significant proportion of newly released As is prone to re-adsorption onto the
soil surface and becomes highly mobile and bioaccessible. While inorganic acids
and chelating agents had marginal effects on the fate of remaining As, organic
ligands (citrate, oxalate, or pyrophosphate) probably destabilized the bonding of
geogenic As and increased its mobility/bioaccessibility despite marginal
extraction. The applicability of chemical extraction of geogenic As is
questionable regardless of chemical agents, thus proper management of the As
containing soil by containment or physical encapsulation may be considered before
land development.
PMID- 28494294
TI - Quantifying the impact of climate change on crop yield and water footprint of
rice in the Nam Oon Irrigation Project, Thailand.
AB - Northeast Thailand makes a significant contribution to fragrant and high-quality
rice consumed within Thailand and exported to other countries. The majority of
rice is produced in rainfed conditions while irrigation water is supplied to rice
growers in the dry season. This paper quantifies the potential impact of climate
change on the water footprint of rice production using the DSSAT (CERES-Rice)
crop growth model for the Nam Oon Irrigation Project located in Northeast
Thailand. Crop phenology data was obtained from field experiments and used to set
up and validate the CERES-Rice model. The present and future water footprint of
rice, the amount of water evaporated during the growing period, was calculated
under current and future climatic condition for the irrigation project area. The
outputs of three regional climate models (ACCESS-CSIRO-CCAM, CNRM-CM5-CSIRO-CCAM,
and MPI-ESM-LR-CSIRO-CCAM) for scenarios RCP 4.5 and RCP 8.5 were downscaled
using quantile mapping method. Simulation results show a considerably high
increase in the water footprint of KDML-105 and RD-6 rice varieties ranging from
56.5 to 92.2% and 27.5 to 29.7%. respectively for the future period under RCP
4.5, and 71.4 to 76.5% and 27.9 to 37.6%, respectively under RCP 8.5 relative to
the simulated baseline water footprint for the period 1976-2005. Conversely, the
ChaiNat-1 variety shows a decrease in projected water footprint of 42.1 to 39.4%
under RCP 4.5 and 38.5 to 31.7% under RCP 8.5. The results also indicate a huge
increase in the future blue water footprint, which will consequently cause a high
increment in the irrigation water requirement in order to meet the plant's
evaporation demand. The research outcome highlights the importance of proper
adaptation strategies to reduce or maintain acceptable water footprints under
future climate conditions.
PMID- 28494295
TI - Using a multi-criteria analysis to identify rivers with hydromorphological
restoration priority: Braided rivers in the south-eastern Subcarpathians
(Romania).
AB - In order to systematically plan river restoration actions at a regional scale,
this paper develops a multi-criteria analysis that classifies rivers, based on
their priority for hydromorphological restoration. This priority is defined by
severe human pressures within the erodible corridor of the river, drastic
alteration of the stream channel, and low intensity of river pattern functioning.
Based on relevant indicators for three groups of features (human pressures,
channel changes, and river functionality), a Hydromorphological Restoration
Priority Index (HRPI) was designed. The high values (>66%) of HRPI reflect an
urgent need for hydromorphological restoration while low values (<33%) reveal a
less immediate necessity for restoration. The proposed methodology was applied on
braided sectors of rivers crossing the south-eastern (Curvature) Subcarpathians
(Romania). The values of the total HRPI ranged between 21% (Zabraut River) and
almost 44% (Prahova River). According to our results, most of the analyzed
sectors have a low need for hydromorphological restoration of the braided
pattern, while some have a moderate necessity for restoration. Whereas the
Prahova River has the highest HRPI, it should be given priority for restoration
at a regional scale, which corresponds to the objectives of River Basin
Management Plans for the interval beyond 2021.
PMID- 28494297
TI - Episodic acidification of 5 rivers in Canada's oil sands during snowmelt: A 25
year record.
AB - Episodic acidification during snowmelt is a natural phenomenon that can be
intensified by acidic deposition from heavy industry. In Canada's oil sands
region, acid deposition is estimated to be as much as 5% of the Canadian total
and large tracks of northeastern Alberta are considered acid-sensitive because of
extensive peatland habitats with poorly weathered soils. To identify the
frequency, duration and severity of acidification episodes during snowmelt (the
predominant hydrological period for delivery of priority pollutants from
atmospheric oil sands emissions to surface waters), a 25-year record (1989 to
2014) of automated water quality data (pH, temperature, conductivity) was
assembled for 3 rivers along with a shorter record (2012-2014) for another 2
rivers. Acidic episodes (pH<7, ANC<0) were recorded during 39% of all 83 snowmelt
events. The severity (duration x magnitude) of episodic acidification increased
exponentially over the study period (r2=0.56, P<0.01) and was strongly correlated
(P<0.01) with increasing maximum air temperature and weakly correlated with
regional land development (P=0.06). Concentrations of aluminum and 11 priority
pollutants (Sb, As, Be, Cd, Cr, Cu, Pb, Se, Ag, Tl and Zn) were greatest (P<0.01)
during low (<6.5) pH episodes, particularly when coincident with high discharge,
such that aluminum and copper concentrations were at times high enough to pose a
risk to juvenile rainbow trout (Oncorhynchus mykiss). Although low pH (pH<6.5)
was observed during only 8% of 32 acidification episodes, when present, low pH
typically lasted 10days. Episodic surface water acidification during snowmelt,
and its potential effects on aquatic biota, is therefore an important
consideration in the design of long-term monitoring of these typically alkaline
(pH=7.72+/-0.05) rivers.
PMID- 28494296
TI - Quantification of ozone exposure- and stomatal uptake-yield response
relationships for soybean in Northeast China.
AB - High ground-level O3 is a new threat to agricultural production in Northeast
China with the increasing ambient O3 concentration. Little is known about its
impacts on soybean production in this key agricultural region. Accumulated O3
exposure-response and stomatal O3 flux-response relationships were developed
during two continuous growing seasons to evaluate O3-induced yield reduction of
four typical soybean cultivars in Northeast China. Results showed that critical
levels of AOT40 (accumulated hourly O3 concentrations over a threshold of
40nmol.mol-1), SUM06 (sum of all hourly average O3 concentrations over
0.06MUmol.mol-1) and W126 (sum of O3 concentrations weighted by a sigmoidal
function) in relation to 5% reduction in relative seed yield were 4.2, 7.6 and
6.8MUmol.mol-1.h, respectively. The effect of O3 on plants was influenced by leaf
position in canopy. An improved Jarvis stomatal conductance model including leaf
(node) position fitted well with field measurements. The best linear relationship
between stomatal O3 flux and relative soybean yield was obtained when phytotoxic
ozone dose was integrated over a threshold of 9.6nmol.m-2.s-1 (POD9.6) to
represent the detoxification capacity of soybean. POD9.6 and the commonly used
POD6 in relation to 5% reduction in relative seed yield of soybean were 0.9mmol.m
2 and 1.8mmol.m-2, respectively. O3 concentrations above ~38nmol.mol-1
contributed to POD9.6 and caused seed yield loss in soybean. Current annual yield
loss of soybean at ambient O3 was estimated to range between 23.4% and 30.2%. The
O3 dose-response relationships and corresponding thresholds obtained here will
benefit regional O3 risk assessment on soybean production in Northeast China.
PMID- 28494298
TI - Remediation of PAH polluted soils using a soil microbial fuel cell: Influence of
electrode interval and role of microbial community.
AB - The soil microbial fuel cells (SMFCs) were constructed to remediate soils
contaminated by polycyclic aromatic hydrocarbons (PAHs). With a maximum power
density of 12.1mWm-2 and an internal resistance of 470Omega, a closed SMFC showed
electricity generation comparable to that by an open SMFC after 175days of
operation and meanwhile increased the removal rates of anthracene, phenanthrene,
and pyrene to 54.2+/-2.7%, 42.6+/-1.9% and 27.0+/-2.1% from 20.8+/-1.1%, 17.3+/
1.2% and 11.7+/-0.9%, respectively, by the open SMFC. Both the electricity
generation and the removal of PAHs increased with the decreased electrode
interval. When the electrode interval ranged between 4cm and 10cm, the more
closely the electrodes were positioned, the more efficient the electricity
generation and removal of PAHs became. Dominated by the genus of Geobacter, the
SMFC was enriched in electrogenic bacteria at the anode surface, and the growth
of certain microbes other than electrogenic bacteria in the soil was improved by
electrical stimulation. This finding reveals the critical mechanism underlying
electricity generation and improved the removal of PAHs.
PMID- 28494299
TI - Mycorrhization protects Betula pubescens Ehr. from metal-induced oxidative stress
increasing its tolerance to grow in an industrial polluted soil.
AB - In recent years, the use of woody plants in phytoremediation has gained
popularity due to their high biomass production and their association with
mycorrhizal fungi, which can improve their survival and development rates under
stress conditions. In this study, mycorrhized and non-mycorrhized white birch
plants (Betula pubescens Ehr.) were grown in control and a metal-polluted
industrial soil. After 60days of culture, plant growth and metal accumulation,
the content of photosynthetic pigments and oxidative-stress markers, as well as
the enzymatic activities and gene expressions of antioxidant enzymes were
measured. According to our results, mycorrhized birch plants grown in control
soil showed an increased activity and gene expression of catalase and ascorbate
peroxidase, along with hydrogen peroxide overproduction, which could support the
importance of the reactive oxygen species as signaling molecules in the
regulation of plant-fungus interactions. Additionally, in polluted soil
mycorrhized plants had higher biomass but lower metal accumulation, probably
because the symbiotic fungus acted as a barrier to the entrance of metals into
the host plants. This behavior led to mitigation in the oxidative challenge,
reduced hydrogen peroxide content and diminished activities of the antioxidant
enzymes in comparison to non-mycorrhized plants.
PMID- 28494300
TI - Behaviour of the main nonsteroidal anti-inflammatory drugs in a membrane
bioreactor treating urban wastewater at high hydraulic- and sludge-retention
time.
AB - The behaviour and removal efficiency of ibuprofen (IBU), diclofenac (DCF),
ketoprofen (KPF), and naproxen (NPX) during the real urban wastewater treatment
by an experimental full-scale MBR working at high sludge and hydraulic retention
time (SRT, HRT) were determined. The MBR worked in denitrification/nitrification
conformation at 35.4h of HRT (Q=0.45m3/h), 37 d of SRT and a recirculation flow
rate of 4Q. The experiments were made under steady-state conditions, reaching a
biodegradable organic matter removal higher than 99.5%. The MBR system showed
similar removal capacity for IBU, NPX, and KTP (>95%), whose main transformation
occurred in the aerobic reactor with a low contribution from the anoxic reactor.
The system worked with complete nitrification, also achieving an effective
retention of the unbiodegradable organic matter due to recirculation. DCF removal
was low with negative removal yields for several samplings. Both removal and
increase transformation of DCF also occurred in the aerobic reactor, this not
being observed in the anoxic one. DCF tends to accumulate in the system and to be
recirculated. Thus, during the sampling in which DCF influent concentration
decreases, removal yields turn negative. The increase of DCF concentration in the
aerobic bioreactor also contributes to the negative removal yields.
PMID- 28494301
TI - Transformation of hazardous lead into lead ferrite ceramics: Crystal structures
and their role in lead leaching.
AB - This study quantitatively determined the transformation of lead into lead ferrite
ceramics and examined the influence of structural defects in lead ferrites (i.e.
Pb2Fe2O5, PbFe4O7 and PbFe12O19) on lead leaching. Mechanisms of metal
incorporation were examined from quantifying the phase compositions of lead
ferrites in the products of sintering lead oxide with hematite. At low
temperature of 700 degrees C, Pb was preferentially incorporated into the
Pb2Fe2O5 crystals, and the incorporation efficiency ranged from 25.7 to 97.5%
depending on different Pb/Fe molar ratios. By increasing temperatures to 750-850
degrees C, Pb2Fe2O5 was subsequently reacted with hematite for the formation of
PbFe4O7 and PbFe12O19 in Pb/Fe of 1/4 and 1/12 systems. PbFe12O19 was found to be
the high-temperature (1000 degrees C) stable phase for incorporating lead, and
the incorporation efficiency ranged from 28.6 to 92.1% by different Pb/Fe molar
ratios. Leaching tests demonstrated that PbFe12O19 was more resistant to acid
attack than Pb2Fe2O5 and PbFe4O7. The crystal structural defects in Pb2Fe2O5 and
PbFe4O7 were determined to be the factors influencing their intrinsic phase
durability. On the other hand, PbFe12O19 was relatively free of structural
defects and was found to be the preferred stabilization product to reduce the
environmental hazard posed by lead.
PMID- 28494302
TI - Super high removal capacities of heavy metals (Pb2+ and Cu2+) using CNT
dendrimer.
AB - This research demonstrates the capability of carbon nanotubes (CNT) modified with
four generations of poly-amidoamine dendrimer (PAMAM, G4) to remove Cu2+ and Pb2+
heavy metals from aqueous solution in single and binary component systems.
Uniquely high adsorption capacities for copper and lead, which are 3333 and
4870mg/g respectively, were achieved. FTIR, H1 NMR, Zeta potential, SEM and TEM
techniques were employed for characterizing the synthetic nanocomposite and
indicated that the dendrimer functionalized CNTs have been synthesized. The
effects of several parameters including initial metal ion concentration, solution
pH and the nanocomposite dosage were studied. The experimental data were analyzed
by the Langmuir and Freundlich isotherms and the pseudo-first order and pseudo
second order kinetics models. The maximum adsorption occurred at pH=7. The
adsorption process for Cu2+ and Pb2+ in single and binary component systems fit
the Langmuir and extended Langmuir models respectively. This study also tested
the kinetic sorption of the metals on PAMAM/CNT in single and binary component
metal systems at various metal ions concentrations. The results showed that
PAMAM/CNT nanocomposite was a super-adsorbent, able to uptake uniquely large
quantities of heavy metal from single and binary component liquid phase.
PMID- 28494303
TI - Hemocompatibility of inhaled environmental nanoparticles: Potential use of in
vitro testing.
AB - Hemocompatibility testing is an important part in the evaluation of nano-based
medicines. However, it is not systematically used for the assessment of
environmental particles since they do not come in contact with blood immediately.
Studies on human exposure to air-borne particles and pulmonary exposure of
rodents have reported alterations in blood physiology. It is not clear, whether
these effects are majorly caused by tissue inflammation or translocated particles
in blood. This review addresses the question, if in vitro hemocompatibility
testing could help in the risk evaluation of inhaled particles. Particle blood
concentrations were estimated based on exposure levels, ventilation volume,
deposition rate, lung surface area, and permeability of the alveolar epithelium
to particles. The categories of hemocompatibility, thrombosis, coagulation,
platelets, hematology, and immunology, were introduced. Also, concentrations of
ultrafine particles, silver nanoparticles, carbon nanotubes that caused adverse
effects in human blood samples were compared to the estimated concentrations of
translocated particles. The comparison suggested that, it is unlikely for
translocated nanoparticles to be the sole cause of adverse blood effects.
Nevertheless, the testing of specific hemocompatibility parameters (hemolysis and
clotting) in healthy blood might help to compare biological effect of inhaled
particles containing different amounts of contamination. Testing of samples from
healthy and diseased persons might help to identify pathological dispositions
that increase the possibility of adverse reaction of nanoparticles in blood.
PMID- 28494304
TI - Successful sulfur recovery in low sulfurate compounds obtained from the zinc
industry: Evaporation-condensation method.
AB - The improvement of an evaporation-condensation method allows for successful
recovery of elemental sulfur from sulfide concentrates from the zinc industry.
Elemental sulfur can be obtained with this method in samples with a low (60%)
sulfur content. The effects of heating temperature between 150 degrees C and 250
degrees C and heating time up to 120min on the recovery of sulfur are also
studied. Elemental sulfur obtained in this way is of high purity and therefore,
there is no need for further purification. The treatment of these industrial
residues would help removing sulfur from the environment.
PMID- 28494306
TI - Membranes based on polymer miscibility for selective transport and separation of
metallic ions.
AB - Polymer inclusion membranes (PIM) used for selective transport and separation of
metallic ions have emerged in recent times. Their expansion depends on the method
of preparation and their suitable structure and physico-chemical characteristics.
In this paper, a novel category of membranes for ions separation is reported. The
membranes were synthesized by thermally induced phase separation using a mixture
of polyvinylidene fluoride (PVDF) and cellulose triacetate (CTA) plasticized by
tris(2-ethylhexyl) phosphate (TEHP) and with di-(2-ethylhexyl) phosphoric acid
(D2EHPA) incorporated into the polymer as carrier to increase specific
interactions between polymers. PIM membrane exhibited a hydrophobic (~100 degrees
) and thermally stable up to ~200 degrees C porous homogenous structure. The
transport of Ni(II), Zn(II) and Pb(II) from aqueous solutions was studied by
competitive transport across polymer inclusion membranes (PIM). Competitive
transport of ions in solution across PIM provide the selectivity order: Ni2+
(45%)>Pb2+ (35%)>Zn2+ (5%). A long-term transport experiment was carried out to
study the durability of the system.
PMID- 28494305
TI - Photovoltage response of (XZn)Fe2O4-BiFeO3 (X=Mg, Mn or Ni) interfaces for highly
selective Cr3+, Cd2+, Co2+ and Pb2+ ions detection.
AB - High-photostability fluorescent (XZn)Fe2O4 (X=Mg, Mn or Ni) embedded in BiFeO3
spinel-perovskite nanocomposites were successfully fabricated via a novel bio
induced phase transfer method using shewanella oneidensis MR-1. These
nanocomposites have the near-infrared fluorescence response (XZn or Fe)-O-O-(Bi)
interfaces (785/832nm), and the (XZn)Fe2O4/BiFeO3 lattices with high/low
potentials (572.15-808.77meV/206.43-548.1meV). Our results suggest that heavy
metal ion (Cr3+, Cd2+, Co2+ and Pb2+) d? orbitals hybridize with the paired-spin
X-Zn-Fe d?-d?-d?? orbitals to decrease the average polarization angles (-29.78 to
44.71 degrees ), qualitatively enhancing the photovoltage response selective
potentials (39.57-487.84meV). The fluorescent kinetic analysis shows that both
first-order and second-order equilibrium adsorption isotherms are in line and
meet the Langmuir and Freundlich modes. Highly selective fluorescence detection
of Co2+, Cr3+ and Cd2+ can be achieved using Fe3O4-BiFeO3 (Langmuir mode),
(MgZn)Fe2O4-BiFeO3 and (MnZn)Fe2O4-BiFeO3 (Freundlich mode), respectively. Where
the corresponding max adsorption capacities (qmax) are 1.5-1.94, 35.65 and 43.7
multiple, respectively, being more competitive than that of other heavy metal
ions. The present bio-synthesized method might be relevant for high
photostability fluorescent spinel-perovskite nanocomposites, for design of heavy
metal ion sensors.
PMID- 28494307
TI - A resonance Rayleigh scattering sensor for detection of Pb2+ ions via cleavage
induced G-wire formation.
AB - A resonance Rayleigh scattering (RRS) aptasensor was fabricated for detection of
Pb2+via hairpin-like label-free substrate and G-wire for signal amplification. A
hairpin-like DNA substrate contains a sequence in the loop labeled with
ribonucleobase A and c-myc sequence in the stem. When hybridized with 8-17
DNAzyme in the presence of Pb2+, the sequence in the loop was activated and
cleaved. Hundreds of c-myc sequences departing from the 8-17 DNAzyme yield
nanowires superstructure called G-wire in the presence of Mg2+. The polymer G
wire was demonstrated by the RRS spectrum, polyacrylamide gel electrophoresis,
and AFM. The RRS intensity was enhanced by the product G-wires, and the RRS
signal at 370nm was linear with the logarithm of Pb2+ concentration in the range
of 2.0nM to 5.0MUM. This method was selective for Pb2+ even coexisting with other
metal ions at high concentrations and was successfully applied to the
determination of Pb2+ in real samples. The aptasensor holds a great promise for
universal RRS sensing platform for sensitive detection of various metal ions just
by changing the sequence of the probe in the loop and DNAzyme.
PMID- 28494308
TI - Unravelling cadmium toxicity and nitric oxide induced tolerance in Cucumis
sativus: Insight into regulatory mechanisms using proteomics.
AB - Nitric oxide (NO) is a signal molecule that can mediate a wide range of
physiological processes against cadmium (Cd) toxicity in plants. However, little
information can be used to reveal the global and systematic mitigative mechanism
of NO in improving Cd stress tolerance of cucumber plants. In the present study,
we used Isobaric Tag for Relative and Absolute Quantification (iTRAQ) analysis to
identify 1691 proteins, which can be used to determine the role of NO in
regulating the molecular changes of proteome in cucumber leaves exposed to Cd
stress. Several dysregulated key proteins indicated that Cd-induced physiological
deterioration of cucumber leaves were mainly involved in metabolic process,
cellular process, response to stimulus and so on. Metabolic pathway analysis
indicated that several Cd-disruptive pathways were markedly reversed by NO
treatments, including Cd transport and localization, photosynthesis, chlorophyll
metabolism, redox homeostasis, glutathione-mediated Cd detoxification and Ca2+
signaling transduction. Taken together, this iTRAQ analysis provides more
comprehensive insights into the physiological and molecular mechanisms of NO
against Cd toxicity in cucumber plants.
PMID- 28494309
TI - Macroscopic and spectroscopic studies of the enhanced scavenging of Cr(VI) and
Se(VI) from water by titanate nanotube anchored nanoscale zero-valent iron.
AB - Herein, a promising titanate nanotubes (TNT) anchored nanoscale zero-valent iron
(NZVI) nanocomposite (NZVI/TNT) was synthesized, characterized and used for the
enhanced scavenging of Cr(VI) and Se(VI) from water. The structural
identification indicated that NZVI was uniformly loaded on TNT, thereby, the
oxidation and aggregation of NZVI was significantly minimized. The macroscopic
experimental results indicated that NZVI/TNT exhibited higher efficiency as well
as rate on Cr(VI) and Se(VI) scavenging resulted from the good synergistic effect
between adsorption and reduction. Besides, TNT can weaken the inhibitory effect
of co-existing humic acid (HA) and fulvic acid (FA) on the scavenging of Cr(VI)
and Se(VI) by NZVI, since TNT showed strong adsorption for HA and FA that inhibit
potential reactivity. XPS analysis suggested that surface-bound Fe(II) played a
critical role in Cr(VI) and Se(VI) scavenging. XANES analysis demonstrated that
TNT acted as a promoter for the almost complete transformation of Cr(VI) into
Cr(III), and Se(VI) into Se(0)/Se(-II) in NZVI system. EXAFS analysis indicated
that TNT acted as a scavenger for insoluble products, and thus more reactive
sites can be used for Cr(VI) and Se(VI) reduction. The excellent performance of
NZVI/TNT provide a potential material for purification and detoxification of
Cr(VI) and Se(VI) from wastewater.
PMID- 28494310
TI - A novel and facile strategy for highly flame retardant polymer foam composite
materials: Transforming silicone resin coating into silica self-extinguishing
layer.
AB - In this study, a novel strategy was developed to fabricate highly flame retardant
polymer foam composite materials coated by synthesized silicone resin (SiR)
polymer via a facile dip-coating processing. Applying the SiR polymer coating,
the mechanical property and thermal stability of SiR-coated polymer foam (PSiR)
composites are greatly enhanced without significantly altering their structure
and morphology. The minimum oxygen concentration to support the combustion of
foam materials is greatly increased, i.e. from LOI 14.6% for pure foam to LOI 26
29% for the PSiR composites studied. Especially, adjusting pendant group to SiOSi
group ratio (R/Si ratio) of SiRs produces highly flame retardant PSiR composites
with low smoke toxicity. Cone calorimetry results demonstrate that 44-68%
reduction in the peak heat release rate for the PSiR composites containing
different R/Si ratios over pure foam is achieved by the presence of appropriate
SiR coating. Digital and SEM images of post-burn chars indicate that the SiR
polymer coating can be transformed into silica self-extinguishing porous layer as
effective inorganic barrier effect, thus preserving the polymer foam structure
from fire. Our results show that the SiR dip-coating technique is a promising
strategy for producing flame retardant polymer foam composite materials with
improved mechanical properties.
PMID- 28494311
TI - Bromination of petroleum coke for elemental mercury capture.
AB - Activated carbon injection has been proven to be an effective control technology
of mercury emission from coal-fired power plants. Petroleum coke is a waste by
product of petroleum refining with large quantities readily available around the
world. Due to its high inherent sulfur content, petroleum coke is an attractive
raw material for developing mercury capture sorbent, converting a waste material
to a value-added product of important environmental applications. In this study,
petroleum coke was brominated by chemical-mechanical bromination. The brominated
petroleum coke was characterized for thermal stability, mercury capture capacity,
and potential mercury and bromine leaching hazards. Bromine loaded on the
petroleum coke was found to be stable up to 200 degrees C. Even after treating
the brominated petroleum coke for 30min at 600 degrees C, 1/3 bromine remained on
the solid. The sorbent from bromination of sulfur-containing petroleum coke was
shown to be a promising alternative to commercial brominated activated carbon for
capture of elemental mercury from coal combustion flue gases.
PMID- 28494312
TI - Anagyrine desensitization of peripheral nicotinic acetylcholine receptors. A
potential biomarker of quinolizidine alkaloid teratogenesis in cattle.
AB - Anagyrine, a teratogenic quinolizidine alkaloid found in Lupinus spp., is
proposed to undergo metabolism by pregnant cattle to a piperidine alkaloid which
inhibits fetal movement, the putative mechanism behind crooked calf syndrome. The
objective of this study was to test the hypothesis that anagyrine but not
lupanine or sparteine can directly, without metabolism, desensitize nicotinic
acetylcholine receptors (nAChR) in a cell culture model. SH-SY5Y cells expressing
autonomic nAChR, and TE-671 cells expressing fetal muscle-type nAChR were exposed
to lupine alkaloids or Dimethylphenylpiperazinium (DMPP) in log10 molar
increments from 10nM to 100MUM and then to a fixed concentration of acetylcholine
(ACh) (10MUM for SH-SY5Y cells and 1MUM for TE-671 cells) and the responses
measured with a membrane potential sensing dye to assess nAChR activation and
desensitization. The selective ganglionic nAChR agonist DMPP used as a positive
control, was a potent activator and desensitizer of nAChR expressed by SH-SY5Y
cells. Lupanine was a weak agonist and desensitizer in SH-SY5Y cells and
sparteine was without effect. Anagyrine acted as a partial agonist in both cell
lines with EC50 values of 4.2 and 231MUM in SH-SY5Y and TE-671 cells,
respectively. Anagyrine was a desensitizer of nAChR with DC50 values of 6.9 and
139MUM in SH-SY5Y and TE-671 cells, respectively. These results confirm the
hypothesis that anagyrine is a potent and effective desensitizer of nAChR, and
that anagyrine can directly, without metabolism, desensitize nAChR. Moreover,
serum anagyrine concentrations may be a potential biomarker for lupine
teratogenicity in cattle.
PMID- 28494313
TI - Heavy metals translocation and accumulation from the rhizosphere soils to the
edible parts of the medicinal plant Fengdan (Paeonia ostii) grown on a metal
mining area, China.
AB - Fengdan (Paeonia ostii) is one of Chinese 34 famous medicinal materials. This
study investigated the concentrations of Arsenic (As), Chromium (Cr), Cadmium
(Cd), Copper (Cu), Lead (Pb), Iron (Fe), Manganese (Mn), and Zinc (Zn) in
rhizosphere soils, cortex mouton and seeds of Fengdan planted in a metal mining
area, China. The mean concentrations of As, Cd, Cu, and Zn in the rhizosphere
soils were above the limits set by the Chinese Soil Environmental Quality
Standard (GB 15618-1995). The contamination factor (CF) of Cd was >5, while it
was >2for As, Cu, Pb, and Zn in all the soils. The integrated pollution index for
all the soils was >3 and ? 5. Metal concentrations in the edible parts of Fengdan
were in the following decreasing order: Mn>Fe>Zn>Cu>Pb>As>Cr>=Cd. The transfer
factor mean values for As, Cu, Cd and Fe in the cortex moutan of old Fengdan
(over 6 years) were significantly higher than in young Fengdan. Available metal
concentrations, pH and soil organic matter content influenced the metal
concentrations of the cortex moutan. The results indicated that mining and
smelting operations have led to heavy metals contamination of soils and medicinal
parts of Fengdan. The major metal pollutants were elemental Cd, Cu, Pb, and Zn.
Heavy metals mainly accumulated in the cortex moutan of Fengdan. The mean
concentrations of Cd, Cu, and Pb in the old cortex moutan (over 6 years) were
above those of the Chinese Green Trade Standards for Medicinal Plants and
Preparations in Foreign Trade (WM/T2-2004).
PMID- 28494314
TI - Structure and gene cluster of the O-antigen of Escherichia albertii O1 resembling
the O-antigen of Pseudomonas aeruginosa O5.
AB - The O-specific polysaccharide (O-antigen) was obtained by mild acid degradation
of the lipopolysaccharide of Escherichia albertii serotype O1 strain SP20140089
and studied by sugar analysis along with 1D and 2D 1H and 13C NMR spectroscopy.
The following structure was established for the trisaccharide repeating unit of
the O-polysaccharide: ->4)-beta-d-ManpNAc3NAcA-(1 -> 4)-beta-d-GlcpNAm3NAcA-(1 ->
3)-alpha-d-GlcpNAc-(1-> where ManNAc3NAcA and GlcNAm3NAcA indicate 2,3
diacetamido-2,3-dideoxymannuronic acid and 2-acetimidoylamino-3-acetamido-2,3
dideoxyglucuronic acid, respectively. While showing some similarity with O
polysaccharide structures of a group of Pseudomonas aeruginosa serotypes (O2, O5,
O16, O18, and O20), that of E. albertii O1 is unique among known bacterial
polysaccharide structures. The gene cluster for biosynthesis of the O1-antigen
was sequenced and functions of the genes were predicted by comparison with
sequences in the available databases, including those involved in the synthesis
of nucleotide precursors of 2,3-diamino-2,3-dideoxyhexuronic acid derivatives in
P. aeruginosa O5.
PMID- 28494315
TI - Glycoengineering and glycosite-specific labeling of serum IgGs from various
species.
AB - Chemoenzymatic glycoengineering of immunoglobulin G (IgG) catalyzed by Endo-S is
a powerful approach to remodel the heterogeneous N-glycoforms of Fc domain with a
homogeneous synthetic glycan structure for enhanced Fc receptor-mediated effector
functions. The previous researches on the method development mainly focused on
human or humanized IgGs with therapeutic potentials. Here, for the first time we
report the extended application of this method on glycan-remodeling of serum IgGs
from other species including rabbit, mouse, and goat. Harnessing an azido-tagged
non-natural N-glycan substrate and successive click reaction, glycosite-specific
fluorescent labeling of IgGs was enabled. This study provided a new avenue for
glycoengineering and Fc-specific labeling of IgGs with minimized influence on
antigen-binding domains, and this method was adaptive to thousands of commercial
antibody reagents from various species with great application potentials.
PMID- 28494316
TI - Combinatorial chemistry in drug discovery.
AB - Several combinatorial methods have been developed to create focused or diverse
chemical libraries with a wide range of linear or macrocyclic chemical molecules:
peptides, non-peptide oligomers, peptidomimetics, small-molecules, and natural
product-like organic molecules. Each combinatorial approach has its own unique
high-throughput screening and encoding strategy. In this article, we provide a
brief overview of combinatorial chemistry in drug discovery with emphasis on
recently developed new technologies for design, synthesis, screening and decoding
of combinatorial library. Examples of successful application of combinatorial
chemistry in hit discovery and lead optimization are given. The limitations and
strengths of combinatorial chemistry are also briefly discussed. We are now in a
better position to truly leverage the power of combinatorial technologies for the
discovery and development of next-generation drugs.
PMID- 28494317
TI - Consumer evaluations of processed meat products reformulated to be healthier - A
conjoint analysis study.
AB - Recent innovations in processed meats focus on healthier reformulations through
reducing negative constituents and/or adding health beneficial ingredients. This
study explored the influence of base meat product (ham, sausages, beef burger),
salt and/or fat content (reduced or not), healthy ingredients (omega 3, vitamin
E, none), and price (average or higher than average) on consumers' purchase
intention and quality judgement of processed meats. A survey (n=481) using
conjoint methodology and cluster analysis was conducted. Price and base meat
product were most important for consumers' purchase intention, followed by
healthy ingredient and salt and/or fat content. In reformulation, consumers had a
preference for ham and sausages over beef burgers, and for reduced salt and/or
fat over non reduction. In relation to healthy ingredients, omega 3 was preferred
over none, and vitamin E was least preferred. Healthier reformulations improved
the perceived healthiness of processed meats. Cluster analyses identified three
consumer segments with different product preferences.
PMID- 28494318
TI - Moving beyond description: Closing the health equity gap by redressing racism
impacting Indigenous populations.
PMID- 28494319
TI - No baby booms or birth sex ratio changes following Fifty Shades of Grey in the
United States.
AB - INTRODUCTION: The Fifty Shades of Grey (FSOG) trilogy were publicised by the
media as inflaming increased coital activity, and that this would result a baby
boom. Furthermore, increased coital activity skews the sex ratio at birth (M/T)
toward male births. This study was carried out in order to ascertain whether
there were any spikes in total births or in M/T in the United States (US) circa
nine months following the FSOG books. METHODS: Monthly male and female births for
the US were obtained directly from the website of the Centre for Disease Control
(01/2007-12/2015). RESULTS: This study analysed 36,499,163 live births (M/T
0.5117, 95% CI 0.5116-0.5119). There are no discernible spikes in total births or
M/T at annual level, or circa nine months after FSOG book releases i.e. 04/2012
and 01/2013. DISCUSSION: The absence of spikes in births or M/T may have been due
to exaggeration of the FSOG effect, it may only have provoked planned
pregnancies, or modern contraception was sufficiently effective to prevent extra
conceptions. The media build-up may also have stimulated a Hawthorne effect, with
FSOG-affected individuals employing effective contraception. This study
highlights the importance of measurement of cause and effect since anticipated
results may not always ensue from events.
PMID- 28494320
TI - Can segmental model reductions quantify whole-body balance accurately during
dynamic activities?
AB - When investigating whole-body balance in dynamic tasks, adequately tracking the
whole-body centre of mass (CoM) or derivatives such as the extrapolated centre of
mass (XCoM) can be crucial but add considerable measurement efforts. The aim of
this study was to investigate whether reduced kinematic models can still provide
adequate CoM and XCoM representations during dynamic sporting tasks. Seventeen
healthy recreationally active subjects (14 males and 3 females; age, 24.9+/
3.2years; height, 177.3+/-6.9cm; body mass 72.6+/-7.0kg) participated in this
study. Participants completed three dynamic movements, jumping, kicking, and
overarm throwing. Marker-based kinematic data were collected with 10
optoelectronic cameras at 250Hz (Oqus Qualisys, Gothenburg, Sweden). The
differences between (X)CoM from a full-body model (gold standard) and (X)CoM
representations based on six selected model reductions were evaluated using a
Bland-Altman approach. A threshold difference was set at +/-2cm to help the
reader interpret which model can still provide an acceptable (X)CoM
representation. Antero-posterior and medio-lateral displacement profiles of the
CoM representation based on lower limbs, trunk and upper limbs showed strong
agreement, slightly reduced for lower limbs and trunk only. Representations based
on lower limbs only showed less strong agreement, particularly for XCoM in
kicking. Overall, our results provide justification of the use of certain model
reductions for specific needs, saving measurement effort whilst limiting the
error of tracking (X)CoM trajectories in the context of whole-body balance
investigation.
PMID- 28494321
TI - Objective assessment of movement competence in children using wearable sensors:
An instrumented version of the TGMD-2 locomotor subtest.
AB - Movement competence (MC) is defined as the development of sufficient skill to
assure successful performance in different physical activities. Monitoring
children MC during maturation is fundamental to detect early minor delays and
define effective intervention. To this purpose, several MC assessment batteries
are available. When evaluating movement strategies, with the aim of identifying
specific skill components that may need improving, widespread MC assessment is
limited by high time consumption for scoring and the need for trained operators
to ensure reliability. This work aims to facilitate and support the assessment by
designing, implementing and validating an instrumented version of the TGMD-2
locomotor subtest based on Inertial Measurement Units (IMUs) to quantify MC in
children rapidly and objectively. 45 typically developing children, aged 6-10,
performed the TGMD-2 locomotor subtest (six skills). During the tests, children
wore five IMUs mounted on lower back, on ankles and on wrists. Sensor and video
recordings of the tests were collected. Three expert evaluators performed the
standard assessment of TGMD-2. Using theoretical and modelling approaches,
algorithms were implemented to automatically score children tests based on IMUs'
data. The automatic assessment, compared to the standard one, showed an agreement
higher than 87% on average on the entire group for each skill and a reduction of
time for scoring from 15 to 2min per participant. Results support the use of IMUs
for MC assessment: this approach will allow improving the usability of MC
assessment, supporting objectively evaluator decisions and reducing time
requirement for the evaluation of large groups.
PMID- 28494322
TI - Constituent Lower Extremity Work (CLEW) approach: A novel tool to visualize joint
and segment work.
AB - Work can reveal the mechanism by which movements occur. However, work is less
physically intuitive than more common clinical variables such as joint angles,
and are scalar quantities which do not have a direction. Therefore, there is a
need for a clearly reported and comprehensively calculated approach to easily
visualize and facilitate the interpretation of work variables in a clinical
setting. We propose the Constituent Lower Extremity Work (CLEW) approach, a
general methodology to visualize and interpret cyclic tasks performed by the
lower limbs. Using six degree-of-freedom power calculations, we calculated the
relative work of the four lower limb constituents (hip, knee, ankle, and distal
foot). In a single pie chart, the CLEW approach details the mechanical cost-of
transport, the percentage of positive and negative work performed in stance phase
and swing phase, and the individual contributions of positive and negative work
from each constituent. This approach can be used to compare the constituent-level
adaptations occurring between limbs of individuals with impairments, or within a
limb at different gait intensities. In this article, we outline how to generate
and interpret the CLEW pie charts in a clinical report. As an example of the
utility of the approach, we created a CLEW report using average reference data
from eight unimpaired adult subjects walking on a treadmill at 0.8 statures/s
(1.4m/s) compared with data from the intact and prosthetic limbs of an individual
with a unilateral amputation walking with an above-knee passive prosthesis.
PMID- 28494323
TI - Stress regulation in drug-resistant epilepsy.
AB - The prevalence of psychological distress, especially depressive and anxiety
disorders, is higher in epilepsy than in other chronic health conditions. These
comorbid conditions contribute even more than epileptic seizures themselves to
impaired quality of life in patients with epilepsy (PWE). The link between these
comorbidities and epilepsy appears to have a neurobiological basis, which is at
least partly mediated by stress through psychological and pathophysiological
pathways. The impact of stress in PWE is also particularly important because it
is the most frequently reported seizure trigger. It is therefore crucial for
clinicians to take stress-related conditions and psychiatric comorbidities into
account when managing PWE and to propose clinical support to enhance self-control
of stress. Screening tools have been specially designed and validated in PWE for
depressive disorders and anxiety disorders (e.g. NDDI-E, GAD-7). Other
instruments are useful for measuring stress-related variables (e.g. SRRS, PSS,
SCS, MHLCS, DSR-15, ERP-R, QOLIE-31) in order to help characterize the individual
"stress profile" and thus orientate patients towards the most appropriate
treatment. Management includes both pharmacological treatment and
nonpharmacological methods for enhancing self-management of stress (e.g.
mindfulness-based therapies, yoga, cognitive-behavioral therapies, biofeedback),
which may not only protect against psychiatric comorbidities but also reduce
seizure frequency.
PMID- 28494324
TI - An unexpected diagnosis of primary omental endometrial stromal sarcoma in a
patient with acute right abdominal pain: A case report and review of literature.
AB - INTRODUCTION: Extrauterine Endometrial Stromal Sarcoma (EESS) is an extremely
rare mesenchymal tumour that simulates other pathologies, and therefore poses a
diagnostic challenge. This report outlines a case of EESS arising from the
greater omentum mimicking a colonic tumour, with review of literature.
PRESENTATION OF CASE: A 47-year-old woman, with history of hysterectomy for
menorrhagia and hormone replacement therapy (HRT), presented with right sided
abdominal pain and localized peritonism. On exploratory laparoscopy an omental
tumour, suspected to arise from the transverse colon was identified and biopsied.
The histological features suggested an EESS. Colonoscopy ruled out colonic
lesion. A laparoscopic tumour resection and bilateral salpingo-oophorectomy (BSO)
was performed. Immunohistochemistry confirmed the diagnosis. No additional
lesions or associated endometriosis were found. Resection was followed by
adjuvant medroxyprogesterone-acetate therapy. DISCUSSION: We reviewed 20 cases of
EESS originating from extragenital abdominopelvic organs reported since 1990.
Acute presentation is rare, as well as upper abdominal occurrence. Isolated
omental involvement was previously reported in only one case. Endometriosis is a
risk factor for development of EESS and history and/or histological evidence for
endometriosis is usually present. HRT is another acknowledged risk factor, mostly
on the background of endometriosis. To our knowledge, this is the only report of
EESS occurring in a woman on HRT treatment without background of endometriosis.
CONCLUSION: EESS can occur without endometriosis and HRT may be an aetiological
factor. The condition can mimic a chronic or acute abdominal pathology and
laparoscopic core biopsy is the best way to achieve a diagnosis and formulate
management.
PMID- 28494325
TI - HIV-1 integrase inhibitor resistance among treatment naive patients in the West
of Scotland.
AB - BACKGROUND: Transmitted integrase inhibitor resistance is rare, with only a small
number of cases reported world-wide to date. OBJECTIVES: The aim of this study
was to assess whether transmitted integrase inhibitor resistance has occurred in
Scotland and if so, could there be a case for performing genotypic integrase
resistance testing at baseline. STUDY DESIGN: The study population consisted of
106 treatment naive, newly diagnosed, HIV positive patients. The patient samples
were collected between October 2015 and March 2016 at the time of HIV diagnosis
and prior to initiation of anti-retroviral therapy. The integrase region was
amplified and sequenced. RESULTS: We detected integrase inhibitor resistance
(T66I/T) at baseline in one patient sample. This is a non-polymorphic mutation
seen in patients receiving elvitegravir which confers high-level resistance to
elvitegravir and intermediate resistance to raltegravir. A further 10 patients
had accessory mutations which have minimal or no effect on susceptibility to
integrase inhibitors. CONCLUSIONS: Transmitted integrase inhibitor resistance
remains rare. The results of the present study do not support performing
integrase resistance testing at baseline.
PMID- 28494326
TI - MAIT cells and MR1-antigen recognition.
AB - Mucosal-associated invariant T cells (MAIT cells) are innate-like T cells that
recognise antigens presented by the monomorphic MHC-I related molecule, MR1.
Distinct from the conventional MHC-restricted T cell system, MR1 presents small
molecule precursors, derived from microbial biosynthesis of riboflavin, to
activate the innate MAIT cell effector potential. Recent data demonstrates how:
vitamin B precursors modulate intracellular trafficking of MR1 and impact on MAIT
cell development; variation in the MAIT cell antigen receptor sequence impacts
MR1-antigen recognition; and most notably, how MR1 can capture chemical
identities distinct from riboflavin precursors, including drugs and drug-like
molecules. With mounting evidence demonstrating their roles in immunity and
pathology, understanding the MAIT-MR1-antigen axis may have profound implications
for human diseases.
PMID- 28494327
TI - Magnetic field-induced effects on NMR properties.
AB - In principle, all the NMR observables, spin-spin coupling J, nuclear shielding
sigma and quadrupole coupling q, are magnetic field-dependent. The field
dependence may be classified into two categories: direct and indirect (apparent)
dependence. The former arises from the magnetic field-induced deformation of the
molecular electronic cloud, while the latter stems from a slightly anisotropic
orientation distribution of molecules, due to the interaction between the
anisotropy of the molecular susceptibility tensor and the external magnetic
field. Here we use 1,3,5-D3-benzene as a model system to investigate the indirect
effect on the one-bond 1H-13C and 2H-13C spin-spin couplings (J couplings) and
the 2H quadrupole coupling. Experiments carried out at four magnetic fields (4.7,
9.4, 14.1, and 18.8 T) show that the indirect effect is significant already at
the magnetic fields commonly used in NMR spectrometers. A joint fit of the data
extracted at the different field strengths provides experimental results for the
susceptibility anisotropy, 2H quadrupole coupling constant and the related
asymmetry parameter, as well as the one-bond CH and CD coupling constants
extrapolated to vanishing field strength. The field-induced contributions are
found to exceed the commonly assumed error margins of the latter. The data also
indicate a primary isotope effect on the one-bond CH coupling constant. There is
a tendency to further increase the magnetic field of NMR spectrometers, which
leads to more pronounced indirect contributions and eventually significant direct
effects as well.
PMID- 28494328
TI - Robust stability analysis of quaternion-valued neural networks with time delays
and parameter uncertainties.
AB - This paper addresses the problem of robust stability for quaternion-valued neural
networks (QVNNs) with leakage delay, discrete delay and parameter uncertainties.
Based on Homeomorphic mapping theorem and Lyapunov theorem, via modulus
inequality technique of quaternions, some sufficient conditions on the existence,
uniqueness, and global robust stability of the equilibrium point are derived for
the delayed QVNNs with parameter uncertainties. Furthermore, as direct
applications of these results, several sufficient conditions are obtained for
checking the global robust stability of QVNNs without leakage delay as well as
complex-valued neural networks (CVNNs) with both leakage and discrete delays.
Finally, two numerical examples are provided to substantiate the effectiveness of
the proposed results.
PMID- 28494329
TI - Hopfield networks as a model of prototype-based category learning: A method to
distinguish trained, spurious, and prototypical attractors.
AB - We present an investigation of the potential use of Hopfield networks to learn
neurally plausible, distributed representations of category prototypes. Hopfield
networks are dynamical models of autoassociative memory which learn to recreate a
set of input states from any given starting state. These networks, however, will
almost always learn states which were not presented during training, so called
spurious states. Historically, spurious states have been an undesirable side
effect of training a Hopfield network and there has been much research into
detecting and discarding these unwanted states. However, we suggest that some of
these states may represent useful information, namely states which represent
prototypes of the categories instantiated in the network's training data. It
would be desirable for a memory system trained on multiple instance tokens of a
category to extract a representation of the category prototype. We present an
investigation showing that Hopfield networks are in fact capable of learning
category prototypes as strong, stable, attractors without being explicitly
trained on them. We also expand on previous research into the detection of
spurious states in order to show that it is possible to distinguish between
trained, spurious, and prototypical attractors.
PMID- 28494330
TI - New models to support the professional education of health visitors: A
qualitative study of the role of space and place in creating 'community of
learning hubs'.
AB - BACKGROUND: In response to a policy-driven workforce expansion in England new
models of preparing health visitors for practice have been implemented.
'Community of Learning hubs' (COLHs) are one such model, involving different
possible approaches to student support in clinical practice placements (for
example, 'long arm mentoring' or 'action learning set' sessions). Such models
present opportunities for studying the possible effects of spatiality on the
learning experiences of students and newly qualified health visitors, and on team
relationships more broadly. OBJECTIVES: To explore a 'community of learning hub'
model in health visitor education and reflect on the role of space and place in
the learning experience and professional identity development of student health
visitors. DESIGN: Qualitative research conducted during first year of
implementation. SETTINGS: Three 'community of learning hub' projects based in two
NHS community Trusts in London during the period 2013-2015. PARTICIPANTS:
Managers and leads (n=7), practice teachers and mentors (n=6) and newly qualified
and student health visitors (n=16). METHODS: Semi-structured, audio-recorded
interviews analysed thematically. RESULTS: Participants had differing views as to
what constituted a 'hub' in their projects. Two themes emerged around the spaces
that shape the learning experience of student and newly qualified health
visitors. Firstly, a generalised need for a 'quiet place' which allows pause for
reflection but also for sharing experiences and relieving common anxieties.
Secondly, the role of physical arrangements in open-plan spaces to promote access
to support from more experienced practitioners. CONCLUSIONS: Attention to
spatiality can shed light on important aspects of teaching and learning
practices, and on the professional identities these practices shape and support.
New configurations of time and space as part of educational initiatives can
surface new insights into existing practices and learning models.
PMID- 28494331
TI - Graduate nurses' evaluation of mentorship: Development of a new tool.
AB - AIM: Develop and test an instrument to measure graduate-nurses' perceptions of a
structured mentorship program. BACKGROUND: New graduate nurses may experience
difficulties in the transition from student to practitioner. Mentoring is
commonly used to support graduates. However, there is a lack of published tools
measuring graduate nurses' perceptions of mentorship. As mentoring is resource
intensive, development and testing of a validated tool are important to assist in
determining program effectiveness. METHODS: A pretest-posttest interventional
design was used. Following a critical review of literature and content experts'
input, the 10-item National University Hospital Mentorship Evaluation (NUH ME)
instrument was tested with a convenience sample of 83 graduate nurses.
Psychometric tests included internal reliability, stability, content validity,
and factor analysis. Changed scores were evaluated using paired samples t-test.
RESULTS: Seventy-three graduates (88%) out of a possible 83 completed the pre-and
post-program survey. Internal reliability was excellent with a Cronbach's alpha
of 0.92. Test-retest reliability was stable over time (ICC=0.81). Exploratory
factor analysis supported a 1-factor solution explaining 58.2% of variance.
Paired samples t-test showed statistical significance between the pre- and post
program scores (p<0.001). CONCLUSIONS: The NUH-ME measure was found to be valid
and reliable. Confirmatory Factor Analysis of the tool with different groups of
nursing graduates is required. Mentorship programs can be an effective
recruitment and retention strategy, but are also resource intensive. Measuring
new graduates' perceptions of mentoring contributes to program relevance in
addressing their personal, professional and clinical skill development needs. As
mentoring engages a diverse range of mentors, feedback through measurement may
also positively alter organizational learning culture.
PMID- 28494332
TI - Polymorphism in ABC transporter genes of Dirofilaria immitis.
AB - Dirofilaria immitis, a filarial nematode, causes dirofilariasis in dogs, cats and
occasionally in humans. Prevention of the disease has been mainly by monthly use
of the macrocyclic lactone (ML) endectocides during the mosquito transmission
season. Recently, ML resistance has been confirmed in D. immitis and therefore,
there is a need to find new classes of anthelmintics. One of the mechanisms
associated with ML resistance in nematodes has been the possible role of ATP
binding cassette (ABC) transporters in reducing drug concentrations at receptor
sites. ABC transporters, mainly from sub-families B, C and G, may contribute to
multidrug resistance (MDR) by active efflux of drugs out of the cell. Gene
products of ABC transporters may thus serve as the targets for agents that may
modulate susceptibility to drugs, by inhibiting drug transport. ABC transporters
are believed to be involved in a variety of physiological functions critical to
the parasite, such as sterol transport, and therefore may also serve as the
target for drugs that can act as anthelmintics on their own. Knowledge of
polymorphism in these ABC transporter genes in nematode parasites could provide
useful information for the process of drug design. We have identified 15 ABC
transporter genes from sub-families A, B, C and G, in D. immitis, by comparative
genomic approaches and analyzed them for polymorphism. Whole genome sequencing
data from four ML susceptible (SUS) and four loss of efficacy (LOE) pooled
populations were used for single nucleotide polymorphism (SNP) genotyping. Out of
231 SNPs identified in those 15 ABC transporter genes, 89 and 75 of them were
specific to the SUS or LOE populations, respectively. A few of the SNPs
identified may affect gene expression, protein function, substrate specificity or
resistance development and may be useful for transporter inhibitor/anthelmintic
drug design, or in order to anticipate resistance development.
PMID- 28494333
TI - Implementing monitoring technologies in care homes for people with dementia: A
qualitative exploration using Normalization Process Theory.
AB - BACKGROUND: Ageing societies and a rising prevalence of dementia are associated
with increasing demand for care home places. Monitoring technologies (e.g. bed
monitoring systems; wearable location-tracking devices) are appealing to care
homes as they may enhance safety, increase resident freedom, and reduce staff
burden. However, there are ethical concerns about the use of such technologies,
and it is unclear how they might be implemented to deliver their full range of
potential benefits. OBJECTIVE: This study explored facilitators and barriers to
the implementation of monitoring technologies in care homes. DESIGN: Embedded
multiple-case study with qualitative methods. SETTING: Three dementia-specialist
care homes in North-West England. PARTICIPANTS: Purposive sample of 24 staff
(including registered nurses, clinical specialists, senior managers and care
workers), 9 relatives and 9 residents. METHODS: 36 semi-structured interviews
with staff, relatives and residents; 175h of observation; resident care record
review. Data collection informed by Normalization Process Theory, which seeks to
account for how novel interventions become routine practice. Data analysed using
Framework Analysis. RESULTS: Findings are presented under three main themes: 1.
Reasons for using technologies: The primary reason for using monitoring
technologies was to enhance safety. This often seemed to override consideration
of other potential benefits (e.g. increased resident freedom) or ethical concerns
(e.g. resident privacy); 2. Ways in which technologies were implemented: Some
staff, relatives and residents were not involved in discussions and decision
making, which seemed to limit understandings of the potential benefits and
challenges from the technologies. Involvement of residents appeared particularly
challenging. Staff highlighted the importance of training, but staff training
appeared mainly informal which did not seem sufficient to ensure that staff fully
understood the technologies; 3. Use of technologies in practice: Technologies
generated frequent alarms that placed a burden upon staff, but staff were able to
use their contextual knowledge to help to counter some of this burden. Some
technologies offered a range of data-gathering capabilities, but were not always
perceived as useful complements to practice. CONCLUSION: Implementation of
monitoring technologies may be facilitated by the extent to which the
technologies are perceived to enhance safety. Implementation may be further
facilitated through greater involvement of all stakeholders in discussions and
decision-making in order to deepen understandings about the range of potential
benefits and challenges from the use of monitoring technologies. Staff training
might need to move beyond functional instruction to include deeper exploration of
anticipated benefits and the underlying rationale for using monitoring
technologies.
PMID- 28494334
TI - Coincidence of role expectations between staff and volunteer members of drug free
community coalitions.
AB - Community coalitions have proliferated as a means of addressing a range of
complex community problems. Such coalitions often consist of a small paid staff
and volunteer members. The present study examines one likely contributor to
coalition effectiveness: the degree of agreement on role expectations between
paid staff and volunteer members. Role confusion occurs when paid staff and
volunteers differ in their expectations of who is responsible for accomplishing
specific tasks. Staff and volunteer members from 69 randomly selected Drug Free
Coalitions in the United States as well as 21 Drug Free Coalitions in Connecticut
were asked to respond to an online survey asking about 37 specific coalition
tasks critical for effective coalition functioning and the degree to which paid
staff and/or voluntary members should be responsible for accomplishing each. Our
final sample consisted of 476 individuals from 35 coalitions. Using coalitions as
the unit of analysis, we found significant differences between paid staff and
volunteer coalition members on nine tasks reflecting four domains: meeting
leadership and participation, (2) planning and implementation leadership, (3)
publicity/media relations, and (4) logistical functions. Implications of these
differences and ways that evaluators could help coalitions deal with differing
role expectations were discussed.
PMID- 28494335
TI - Ultrasound-assisted low-density solvent dispersive liquid-liquid microextraction
for the simultaneous determination of 12 new antidepressants and 2 antipsychotics
in whole blood by gas chromatography-mass spectrometry.
AB - Antidepressant drugs are widely used in the treatment of different psychiatric
disorders, as well as in conjunction with antipsychotics for the treatment of
major depressive disorder. In this study, a simple and rapid ultrasound-assisted
low-density solvent dispersive liquid-liquid microextraction (UA-LDS-DLLME)
method was developed for the simultaneous determination of 12 new antidepressants
(norfluoxetine, fluoxetine, fluvoxamine, agomelatine, mirtazapine, moclobemide,
melitracen, N-desmethylmirtazapine, maprotiline, sertraline, citalopram,
paroxetine) and 2 antipsychotics (clozapine and haloperidol) in human whole blood
by gas chromatography-mass spectrometry (GC-MS). Different parameters affecting
the UA-LDS-DLLME were optimized and the optimal conditions were as follows:
100MUL of toluene as extraction solvent, extraction pH 12 and 3min of ultrasound
stirring. Good linearity (R2>=0.991) was obtained at the concentration range of
15-1500ng/mL for norfluoxetine, fluoxetine, fluvoxamine, melitracen, maprotiline
and citalopram, and 5-500ng/mL for agomelatine, mirtazapine, moclobemide, N
desmethylmirtazapine, sertraline, paroxetine, clozapine and haloperidol. The
intra-day and inter-day precision were all less than 10%, and accuracy of intra
day and inter-day were in the range of -12.7% to 7.9% and -13.9 to 11.8%,
respectively. The extraction recoveries of most analytes were more than 60%. The
UA-LDS-DLLME/GC-MS method was demonstrated with acceptable precision, accuracy
and good specificity for the simultaneous determination of 12 antidepressants and
2 antipsychotics, and has been successfully applied in a real case.
PMID- 28494336
TI - Metabolite profiling of flavonols and in vitro antioxidant activity of young
shoots of wild Humulus lupulus L. (hop).
AB - Humulus lupulus L., commonly named hop, is well-known for its sedative and
estrogenic activity. While hop cones are widely characterized, only few works
have been carried out on the young shoots of this plant. In the light of this,
the aim of this study was to identify for the first time the flavonoids present
in young hop shoots and to compare the composition of samples harvested from
different locations in Northern Italy with their antioxidant activity. The
samples were extracted by means of dynamic maceration with methanol. The HPLC
UV/DAD, HPLC-ESI-MS and MS2 analysis were carried out by using an Ascentis C18
column (250*4.6mm I.D., 5MUm), with a mobile phase composed of 0.1M formic acid
in both water and acetonitrile, under gradient elution. Quercetin and kaempferol
glycosides were the main compounds identified and quantified in hop shoot
extracts. Total flavonols ranged from 2698+/-185 to 517+/-48MUg/g (fresh weight).
The antioxidant activity was determined by means of the radical scavenging
activity assay against diphenylpicrylhydrazyl (DPPH) and by using a
photochemiluscence assay with a Photochem(r) apparatus. The results showed that
hop shoots represent a new source of flavonols; therefore, they can be useful for
a possible incorporation in the diet as a functional food or applied in the
nutraceutical ambit.
PMID- 28494337
TI - Quantification of apigenin trimethyl ether in rat plasma by liquid chromatography
tandem mass spectrometry: Application to a pre-clinical pharmacokinetic study.
AB - Apigenin trimethyl ether (5,7,4'-trimethoxyflavone, ATE) is a naturally occurring
polymethoxyflavone with a wide range of health-promoting activities. In this
study, a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS)
method was developed and validated for the quantification of ATE in rat plasma.
Protein precipitation was applied as plasma clean-up procedure; the electrospray
ionization was operated in its positive ion mode while ATE and formononetin
(internal standard) were measured by multiple reactions monitoring (ATE: m/z
313.1->298.1; formononetin: 269.2->213.3). This LC-MS/MS method displayed good
selectivity, sensitivity (lower limit of quantification=2.5ng/ml), accuracy (both
intra- and inter-day analytical recovery within 100+/-10%) and precision (both
intra- and inter-day RSD <10%). The matrix effect was found to be insignificant.
The pharmacokinetic profiles of ATE were subsequently examined in Sprague-Dawley
rats after single oral administration (10mg/kg). When given in an aqueous
suspension, ATE was slowly absorbed with quite low plasma exposure (AUC). Fasting
further attenuated its oral absorption and led to ~70% drops in average maximal
plasma concentration (Cmax) and AUC. When dosed in a solution formulated with 2
hydroxypropyl-beta-cyclodextrin, the oral absorption of ATE was substantially
improved with ~500% increases in average Cmax and AUC. Clearly, aqueous
solubility has been identified as a barrier to the oral absorption of ATE. The
information obtained from this study will facilitate further medicinal
exploration on ATE.
PMID- 28494338
TI - Simultaneous analysis of regorafenib and sorafenib and three of their metabolites
in human plasma using LC-MS/MS.
AB - A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, performed
by electrospray ionization in positive mode using a triple quadrupole mass
spectrometry, has been developed and validated for the simultaneous determination
of regorafenib (REGO), its two metabolites regorafenib-M2 and regorafenib-M5,
sorafenib (SORA), and its N-oxide metabolite in human plasma. Separation is
achieved on an Hypersil Gold(r) column using a gradient elution of 10mM ammonium
formate containing 0.1% formic acid (A) and acetonitrile containing 0.1% formic
acid (B) at a flow rate of 0.3mL/min. After addition of two internal standards
and a protein precipitation, the supernatant is diluted two-fold in a 0.1% (v/v)
formic acid solution. Two selected reaction monitoring transitions are used, for
each analyte, one for quantitation and the second one for confirmation. The
standard curves are ranged from 50 to 5 000ng/mL for REGO and its metabolites and
80 to 5 000ng/mL for SORA and its metabolite and were fitted to a 1/x weighted
linear regression model. The method also showed satisfactory results in terms of
sensitivity, specificity, precision (intra- and inter-day CV from 2.4 to 10.2%),
accuracy (from 91.0 to 111.7%), recovery as well as stability of the analytes
under various conditions. The method is usually used in clinical practice in
order to improve the SORA treatment for renal carcinoma, REGO treatment for
colorectal cancer and both for hepatocellular carcinoma.
PMID- 28494339
TI - Application of protein A-modified capillary-channeled polymer polypropylene
fibers to the quantitation of IgG in complex matrices.
AB - Polypropylene (PP) capillary-channeled polymer (C-CP) fibers loaded with
recombinant Staphyloccocus aureus protein A (rSPA) were used as an affinity
chromatography stationary phase for the quantitation of immunoglobulin G (IgG) in
complex biological matrices. Optimization of the chromatographic method regarding
mobile phase components and load/elution conditions was performed. The six-minute
analysis, including a load step with 12mM phosphate at pH 7.4, an elution step
with 0.025% phosphoric acid and a re-equilibration step, was employed for
quantitation of IgG1 from 0.075 to 3.00mgmL-1 in an IgG-free CHO cell supernatant
matrix. Quantification of IgG1 content in a different CHO cell line was
accomplished using the external calibration curve as well as using a standard
addition approach. The high level of agreement between the two approaches
suggests that the protein A-modified C-CP fiber phase is immune from matrix
effects due to concomitant species such as host cell proteins (HCPs), host cell
DNA, media components and other leachables and extractables. The inter-day and
intra-day precision of the method were 3.1 and 3.5%RSD respectively for a single
column. Column-to-column variability was 1.31 and 6.62%RSD for elution time and
peak area, respectively, across columns prepared in different batches. The method
reported here is well-suited for IgG analysis in complex harvest cell culture
media in both the development and production environments.
PMID- 28494340
TI - Simple and rapid quantification of vancomycin in serum, urine and
peritoneal/pleural effusion via UHPLC-MS/MS applicable to personalized antibiotic
dosing research.
AB - Management of the therapy of life-threatening bacterial infection is extremely
based on an optimal antibiotic treatment. Achieving the correct vancomycin dosage
in blood and target tissues can be complicated in special situations, e.g., where
large fluid sequestration and/or acute renal failure occur. A UHPLC-MS/MS method
operating in electrospray (ESI) positive ion mode was applied for the
determination of vancomycin in serum, urine and peritoneal/pleural effusion.
Sample pretreatment was composed of dilution and simple protein precipitation
where only a small volume (50MUL) of serum, urine or peritoneal/pleural effusion
was required. The separation of vancomycin was performed on a Meteoric Core C18
BIO column (100*4.6mm, 2.7MUm) by gradient elution with 0.1% formic acid in water
and acetonitrile. The total time of analysis was 4.5min. The method was found to
be linear in the range of 2-60MUM (or 0.5-10MUM) for serum, 0.27-10MUM (or 2
60MUM) for peritoneal/pleural effusion and 25-300MUM for urine, which was
adequate for the determination of vancomycin in patient samples. The intra- and
inter-day precision was below 8% RSD, and accuracy was from 89 to 104%. The
UHPLC/MS-MS method offers a fast and reliable approach to determine vancomycin
concentrations in three different human body fluid samples (serum, urine and
peritoneal/pleural effusion) with a simple sample pretreatment that was the same
for all selected specimens. This method should be applicable to large sample
series in clinical (pharmacokinetic/pharmacodynamic) studies.
PMID- 28494341
TI - Dyospiros kaki phenolics inhibit colitis and colon cancer cell proliferation, but
not gelatinase activities.
AB - Polyphenols from persimmon (Diospyros kaki) have demonstrated radical-scavenging
and antiinflammatory activities; however, little is known about the effects of
persimmon phenolics on inflammatory bowel diseases (IBD) and colorectal cancer
(CRC). Therefore, we aimed in this work to characterize the antiinflammatory and
antiproliferative effects of a persimmon phenolic extract (80% acetone in water),
using an in vivo model of experimental colitis and a model of cancer cell
invasion. Our results show, for the first time, a beneficial effect of a
persimmon phenolic extract in the attenuation of experimental colitis and a
potential antiproliferative effect on cultured colon cancer cells. Administration
of persimmon phenolic extract to mice with TNBS-induced colitis led to a
reduction in several functional and histological markers of colon inflammation,
namely: attenuation of colon length decrease, reduction of the extent of visible
injury (ulcer formation), decrease in diarrhea severity, reduced mortality rate,
reduction of mucosal hemorrhage and reduction of general histological features of
colon inflammation. In vitro studies also showed that persimmon phenolic extract
successfully impaired cell proliferation and invasion in HT-29 cells. Further
investigation showed a decreased expression of COX-2 and iNOS in the colonic
tissue of colitis mice, two important mediators of intestinal inflammation, but
there was no inhibition of the gelatinase MMP-9 and MMP-2 activities. Given the
role of inflammatory processes in the progression of CRC and the important link
between inflammation and cancer, our results highlight the potential of persimmon
polyphenols as a pharmacological tool in the treatment of patients with IBD.
PMID- 28494342
TI - Genome sequence variation among isolates of monkey B virus (Macacine
alphaherpesvirus 1) from captive macaques.
AB - Complete genome sequences of 19 strains of monkey B virus (Macacine
alphaherpesvirus 1; BV) isolated from several macaque species were determined. A
low level of sequence variation was present among BV isolates from rhesus
macaques. Most variation among BV strains isolated from rhesus macaques was
located in regions of repetitive or quasi-repetitive sequence. Variation in
coding sequences (polypeptides and miRNAs) was minor compared to regions of non
coding sequences. Non-coding sequences in the long and short repeat regions of
the genome did however exhibit islands of conserved sequence. Oral and genital
isolates from a single monkey were identical in sequence and varied only in the
number of iterations of repeat units in several areas of repeats. Sequence
variation between BV isolates from different macaque species (different BV
genotypes) was much greater and was spread across the entire genome, confirming
the existence of different genotypes of BV in different macaque species.
PMID- 28494343
TI - Gene end-like sequences within the 3' non-coding region of the Nipah virus genome
attenuate viral gene transcription.
AB - The regulation of transcription during Nipah virus (NiV) replication is poorly
understood. Using a bicistronic minigenome system, we investigated the
involvement of non-coding regions (NCRs) in the transcriptional re-initiation
efficiency of NiV RNA polymerase. Reporter assays revealed that attenuation of
NiV gene expression was not constant at each gene junction, and that the
attenuating property was controlled by the 3' NCR. However, this regulation was
independent of the gene-end, gene-start and intergenic regions. Northern blot
analysis indicated that regulation of viral gene expression by the phosphoprotein
(P) and large protein (L) 3' NCRs occurred at the transcription level. We
identified uridine-rich tracts within the L 3' NCR that are similar to gene-end
signals. These gene-end-like sequences were recognized as weak transcription
termination signals by the viral RNA polymerase, thereby reducing downstream gene
transcription. Thus, we suggest that NiV has a unique mechanism of
transcriptional regulation.
PMID- 28494344
TI - PA-X protein contributes to virulence of triple-reassortant H1N2 influenza virus
by suppressing early immune responses in swine.
AB - Previous studies have identified a functional role of PA-X for influenza viruses
in mice and avian species; however, its role in swine remains unknown. Toward
this, we constructed PA-X deficient virus (Sw-FS) in the background of a Triple
reassortment (TR) H1N2 swine influenza virus (SIV) to assess the impact of PA-X
in viral virulence in pigs. Expression of PA-X in TR H1N2 SIV enhanced viral
replication and host protein synthesis shutoff, and inhibited the mRNA levels of
type I IFNs and proinflammatory cytokines in porcine cells. A delay of
proinflammatory responses was observed in lungs of pigs infected by wild type SIV
(Sw-WT) compared to Sw-FS. Furthermore, Sw-WT virus replicated and transmitted
more efficiently than Sw-FS in pigs. These results highlight the importance of PA
X in the moderation of virulence and immune responses of TR SIV in swine, which
indicated that PA-X is a pro-virulence factor in TR SIV in pigs.
PMID- 28494345
TI - Weight gain after STN-DBS: The role of reward sensitivity and impulsivity.
AB - Weight gain has been reported after deep brain stimulation of the subthalamic
nucleus (STN-DBS), a widely used treatment for Parkinson's disease (PD). This
nucleus has been repeatedly found to be linked both to reward and to inhibitory
control, two key aspects in the control of food intake. In this study, we
assessed whether weight gain experienced by patients with PD after STN-DBS, might
be due to an alteration of reward and inhibitory functions. Eighteen patients
with PD were compared to eighteen healthy controls and tested three times: before
surgery, in ON medication and after surgery, respectively five days after the
implantation in ON medication/OFF stimulation and at least three months after
surgery in ON medication/ON stimulation. All participants were assessed for
depression (Beck Depression Inventory), anhedonia (Snaith-Hamilton Pleasure
Scale) and impulsiveness (Barratt Impulsiveness Scale). They performed a battery
of tests assessing food reward sensitivity (Liking, Wanting and Preference) and a
food go/no-go task. Results showed that body weight significantly increased after
STN-DBS. A few days after surgery, patients were slower and more impulsive in the
go/no-go task, showed a higher preference for high calorie (HC) foods and rated
foods as less tasty. Months after subthalamic stimulation, the performance on the
go/no-go task improved while no differences were observed in reward sensitivity.
Interestingly, weight gain resulted greater in patients with higher levels of
attentional impulsiveness pre-surgery, higher wanting for low calorie (LC) foods
and impulsivity in the go/no-go task in ON medication/ON stimulation. However,
only wanting and attentional impulsivity significantly predicted weight change.
Furthermore, weight gain resulted associated with the reduction of l-Dopa after
surgery and disease's duration. In conclusion, our findings are consistent with
the view that weight gain in PD after STN-DBS has a multifactorial nature, which
reflects the complex functional organization of the STN.
PMID- 28494346
TI - Glutamatergic and neural dysfunction in postpartum depression using magnetic
resonance spectroscopy.
AB - Although postpartum depression (PPD) is a prevalent subtype of major depressive
disorder, neuroimaging studies on PPD are rare, particularly those identifying
neurochemical abnormalities obtained by proton magnetic resonance spectroscopy
(1H-MRS). The dorsolateral prefrontal (DLPF) and the anterior cingulate gyrus
(ACG) are part of the neural pathways involved in executive functions and
emotional processing, and both structures have been implicated in the
neurobiology of depressive disorders. This study aimed to evaluate brain
metabolites abnormalities in women with PPD compared with healthy postpartum (HP)
women. Thirty-six PPD (34 without antidepressants) and 25 HP women underwent a 1H
MRS acquired on a 3-T MRI system, with the volume of interest positioned in ACG
and DLPF. An ANCOVA was conducted with age, postpartum time, and contraceptive
type as covariates. PPD group presented significantly lower Glutamate+Glutamine
(Glx, -0.95mM) and N-acetylaspartate+N-acetylaspartylglutamate (NAA, -0.60mM)
values in DLPF. There were no significant differences between groups in ACG, but
we found a significant increase of Glutamate (Glu, 2.18mM) and Glx (1.84mM) in
participants using progestogen-only contraceptives. These findings suggest
glutamatergic dysfunction and neuronal damage in the DLPF of PPD patients,
similarly to other subtypes of depressive disorders. Progestogens seem to
interfere in the neurochemistry of ACG.
PMID- 28494347
TI - Structural brain abnormalities in patients with type I bipolar disorder and
suicidal behavior.
AB - Some studies have identified brain morphological changes in the frontolimbic
network (FLN) in bipolar subjects who attempt suicide (SA). The present study
investigated neuroanatomical abnormalities in the FLN to find a possible neural
signature for suicidal behavior in patients with bipolar disorder type I (BD-I).
We used voxel-based morphometry to compare euthymic patients with BD-I who had
attempted suicide (n=20), who had not attempted suicide (n=19) and healthy
controls (HCs) (n=20). We also assessed the highest medical lethality of their
previous SA. Compared to the participants who had not attempted suicide, the
patients with BD-I who had attempted suicide exhibited significantly increased
gray matter volume (GMV) in the right rostral anterior cingulate cortex (ACC),
which was more pronounced and extended further to the left ACC in the high
lethality subgroup (p<0.05, with family-wise error (FWE) correction for multiple
comparisons using small-volume correction). GMV in the insula and orbitofrontal
cortex was also related to suicide lethality (p<0.05, FWE-corrected). The current
findings suggest that morphological changes in the FLN could be a signature of
previous etiopathogenic processes affecting regions related to suicidality and
its severity in BD-I patients.
PMID- 28494348
TI - Withaferin A Inhibits Prostate Carcinogenesis in a PTEN-deficient Mouse Model of
Prostate Cancer.
AB - We recently demonstrated that AKT activation plays a role in prostate cancer
progression and inhibits the pro-apoptotic function of FOXO3a and Par-4. AKT
inhibition and Par-4 induction suppressed prostate cancer progression in
preclinical models. Here, we investigate the chemopreventive effect of the
phytonutrient Withaferin A (WA) on AKT-driven prostate tumorigenesis in a Pten
conditional knockout (Pten-KO) mouse model of prostate cancer. Oral WA treatment
was carried out at two different doses (3 and 5 mg/kg) and compared to vehicle
over 45 weeks. Oral administration of WA for 45 weeks effectively inhibited
primary tumor growth in comparison to vehicle controls. Pathological analysis
showed the complete absence of metastatic lesions in organs from WA-treated mice,
whereas discrete metastasis to the lungs was observed in control tumors.
Immunohistochemical analysis revealed the down-regulation of pAKT expression and
epithelial-to-mesenchymal transition markers, such as beta-catenin and N
cadherin, in WA-treated tumors in comparison to controls. This result
corroborates our previous findings from both cell culture and xenograft models of
prostate cancer. Our findings demonstrate that the daily administration of a
phytonutrient that targets AKT activation provides a safe and effective treatment
for prostate cancer in a mouse model with strong potential for translation to
human disease.
PMID- 28494349
TI - Trabectedin and Campthotecin Synergistically Eliminate Cancer Stem Cells in Cell
of-Origin Sarcoma Models.
AB - Trabectedin has been approved for second-line treatment of soft tissue sarcomas.
However, its efficacy to target sarcoma initiating cells has not been addressed
yet. Here, we used pioneer models of myxoid/round cell liposarcoma (MRCLS) and
undifferentiated pleomorphic sarcoma (UPS) developed from transformed human
mesenchymal stromal/stem cells (MSCs) to evaluate the effect of trabectedin in
the cell type responsible for initiating sarcomagenesis and their derived cancer
stem cells (CSC) subpopulations. We found that low nanomolar concentrations of
trabectedin efficiently inhibited the growth of sarcoma-initiating cells, induced
cell cycle arrest, DNA damage and apoptosis. Interestingly, trabectedin treatment
repressed the expression of multiple genes responsible for the development of the
CSC phenotype, including pluripotency factors, CSC markers and related signaling
pathways. Accordingly, trabectedin induced apoptosis and reduced the survival of
CSC-enriched tumorsphere cultures with the same efficiency that inhibits the
growth of bulk tumor population. In vivo, trabectedin significantly reduced the
mitotic index of MRCLS xenografts and inhibited tumor growth at a similar extent
to that observed in doxorubicin-treated tumors. Combination of trabectedin with
campthotecin (CPT), a chemotherapeutic drug that shows a robust anti-tumor
activity when combined with alkylating agents, resulted in a very strong
synergistic inhibition of tumor cell growth and highly increased DNA damage and
apoptosis induction. Importantly, the enhanced anti-tumor activity of this
combination was also observed in CSC subpopulations. These data suggest that
trabectedin and CPT combination may constitute a novel strategy to effectively
target both the cell-of-origin and CSC subpopulations in sarcoma.
PMID- 28494350
TI - Liquid chromatography-tandem mass spectrometry quantification of acetamiprid and
thiacloprid residues in butterbur grown under regulated conditions.
AB - An analytical method was developed to quantify the residual levels of the
neonicotinoid insecticides, acetamiprid and thiacloprid, in field-incurred
butterbur samples using liquid chromatography-tandem mass spectrometry (LC
MS/MS). Samples were extracted with acetonitrile and partitioned with
dichloromethane. After partitioning, purification was conducted using a
Florisil(r) cartridge. Linearity of a matrix-matched calibration curve of the two
compounds over a concentration range of 0.004-0.4MUg/g was excellent, with
determination coefficients (R2)>=0.9998. The limits of detection (LOD) and
quantitation (LOQ) for both acetamiprid and thiacloprid were 0.0006 and
0.002mg/kg, respectively. The average recoveries for acetamiprid and thiacloprid
at two spiking levels (0.02 and 0.1mg/kg, i.e., 10*LOQ and 50*LOQ) were between
78.23 to 82.17%, with relative standard deviations (RSDs)<=7.22%. The method was
successfully applied to field-incurred samples treated with a commercial
pesticide product, either once (zero or 7 days before harvest) or twice (0 and 7,
7 and 14, or 14 and 21 days before harvest). The highest and lowest residues were
obtained for the 7 and 0 days' treatment and the 21 and 14 days' treatment,
respectively. The developed method is simple and accurate and can be extrapolated
to other leafy vegetables.
PMID- 28494351
TI - Development and validation of a sensitive UPLC-MS/MS instrumentation and alkaline
nitrobenzene oxidation method for the determination of lignin monomers in wheat
straw.
AB - A method to determine the lignin monomers (p-hydroxybenzaldehyde, vanillin and
syringaldehyde) in plant cell wall of wheat internode was developed and validated
using a high-throughput nitrobenzene oxidation step and ultra performance liquid
chromatography tandem mass spectrometry (UPLC-MS/MS) for quantification. UPLC
analyses were carried out using an reversed phase C18 column (ACQUITY UPLC BEH,
1.7MUm, 2.1*100mm) and gradient elution with water and acetonitrile. This method
was completely validated in terms of analyzing speed, linearity, sensitivity,
limits of detection (LODs) and limits of quantification (LOQs).The three lignin
monomers were successfully separated within 6min and only 2min were required to
regain its equilibrium. The method linearity with regression coefficients values
(R2) greater than 0.997. Additionally, LODs ranged from 0.21 to 0.89MUgL-1 and
LOQs ranged from 0.69 to 2.95MUgL-1. The applicability of this analytical
approach for determining the three lignin monomers was confirmed by the
successful analysis of real samples of wheat stem internodes. The nitrobenzene
oxidation method was used for the analysis of lignin monomers. We have optimized
the treatment temperature (170 degrees C, 1h) and realized the high-throughput
using the microwave digestion instrument. Recovery of this extraction method
ranged from 68.4% to 77.7%. The analysis result showed that the guaiacyl unit (G)
was the major component of lignin and there was a higher content of the syringyl
unit (S) than that of the hydroxybenzyl unit (H).
PMID- 28494352
TI - IL-33 protects murine viral fulminant hepatitis by targeting coagulation hallmark
protein FGL2/fibroleukin expression.
AB - Fulminant hepatitis (FH) is characterized by rapid liver failure and high
mortality. The pathogenesis of viral FH includes virus-induced immune activation,
inflammation, and subsequent hepatic apoptosis and necrosis. However, the
mechanisms that underlie FH progression are unclear. IL-33 is a member of the IL
1-related cytokines, considered to be an "alarmin" that participates in various
diseases, but its precise role in the coagulation of FH is not very clear. In our
study, we found that IL-33 is significantly elevated in mice infected with murine
hepatitis virus strain 3 (MHV-3). This is accompanied by an increase in pro
coagulant fibrinogen-like protein 2 (FGL2) in the liver. Previous studies have
suggested that an increase in FGL2 is diagnostic of FH and liver necrosis, and
animals with no FGL2 had better survivorship during FH. Our studies showed that
IL-33 administration in a MHV-3 infection promoted survival during FH, with a
significant reduction in FGL2 expression and liver inflammation. In vitro IL-33
treatment abrogated MHV-3 and IFN-gamma induced FGL2 expression in RAW264.7 and
THP-1 cells, respectively. In conclusion, our research suggests that IL-33
protects against viral fulminant hepatitis in mice by antagonizing expression of
the pro-coagulant protein FGL2.
PMID- 28494353
TI - Removal of pesticides and ecotoxicological changes during the simultaneous
treatment of triazines and chlorpyrifos in biomixtures.
AB - Biopurification systems constitute a biological approach for the treatment of
pesticide-containing wastewaters produced in agricultural activities, and contain
an active core called biomixture. This work evaluated the performance of a
biomixture to remove and detoxify a combination of three triazine herbicides
(atrazine/terbuthylazine/terbutryn) and one insecticide (chlorpyrifos), and this
efficiency was compared with dissipation in soil alone. The potential enhancement
of the process was also assayed by bioaugmentation with the ligninolytic fungi
Trametes versicolor. Globally, the non-bioaugmented biomixture exhibited faster
pesticide removal than soil, but only in the first stages of the treatment. After
20 d, the largest pesticide removal was achieved in the biomixture, while
significant removal was detected only for chlorpyrifos in soil. However, after 60
d the removal values in soil matched those achieved in the biomixture for all the
pesticides. The bioaugmentation failed to enhance, and even significantly
decreased the biomixture removal capacity. Final removal values were 82.8% (non
bioaugmented biomixture), 43.8% (fungal bioaugmented biomixture), and 84.7%
(soil). The ecotoxicological analysis revealed rapid detoxification (from 100 to
170 TU to <1 TU in 20 d) towards Daphnia magna in the biomixture and soil, and
slower in the bioaugmented biomixture, coinciding with pesticide removal. On the
contrary, despite important herbicide elimination, no clear detoxification
patterns were observed in the phytotoxicity towards Lactuca sativa. Findings
suggest that the proposed biomixture is useful for fast removal of the target
pesticides; even though soil also removes the agrochemicals, longer periods would
be required. On the other hand, the use of fungal bioaugmentation is discouraged
in this matrix.
PMID- 28494354
TI - Development of collection, storage and analysis procedures for the quantification
of cyclic volatile methylsiloxanes in wastewater treatment plant effluent and
influent.
AB - A reliable and accurate method for collection and analysis of
octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5), and
dodecamethylcyclohexasiloxane (D6) in wastewater treatment plant influent,
effluent and surface waters was developed. Due to the use of cyclic volatile
methylsiloxanes (cVMS) in industrial and consumer products including some
personal care products, the wastewater stream represents a potential post-use
disposal route and cVMS may subsequently enter the environment through wastewater
treatment plant effluents. cVMS in the environment has come under increased
regulatory scrutiny with regard to their potential for persistence,
bioaccumulation and toxicity indicating a need for monitoring programs with
reliable analytical methods. The developed method is unique in that it utilizes
low density polyethylene (LDPE) to inhibit loss of cVMS during sampling and
transport to the laboratory. The samples are then processed with a simple solvent
extraction and analyzed by gas chromatography mass spectrometry with stable
isotope internal standard calibration. This method utilizes readily available
laboratory supplies and requires minimal field processing, reducing contamination
potential. Method detection limits of 17 ng/L, 57 ng/L, and 20 ng/L were obtained
for D4, D5, and D6, respectively. Additionally a robust quality control program
was employed to ensure sample integrity. The method described herein can readily
be adopted for use in monitoring studies where the amount of cVMS in water
samples will be quantified.
PMID- 28494355
TI - A hierarchical assembly of flower-like hybrid Turkish black radish peroxidase
Cu2+ nanobiocatalyst and its effective use in dye decolorization.
AB - Effective dye decolorization in wastewater still shows a big challenge. Although
the biological methods, especially using enzymes, offer alternative and effective
process for dye degradation and overcome the limitations of chemical and physical
methods such as the instability, lack of reusability and high cost of free
enzymes strictly, which limit their use in many scientific and technical
applications. Enzymes rapidly lose their activities in aqueous solutions and
against environmental changes due to their very susceptibility and unfavorable
conformations. Herein, we report preparation of the enzyme-inorganic hybrid
nanostructures with flower-like shape consisting of Turkish black radish
peroxidase and Cu2+ metal ions using an encouraging enzyme immobilization
approach. The peroxidase-Cu2+ hybrid nanoflowers (NFs) exhibited enhanced
stability and activity towards various pH values and provided excellent dye
decolorization efficiency for Victoria blue (VB) dye with more than 90% within 1
h. The NFs were also repeatedly used in efficient and caused 77% VB
decolorization efficiency even at tenth cycles. However, to the best of our
knowledge, for the first time, we prepared peroxidase enzyme isolated from
Turkish black radish incorporated NFs and used them for dye decolorization. We
believe that the NFs can be promising materials for dye decolorization in real
wastewater treatment.
PMID- 28494356
TI - Appraising the role of environment friendly chelants in alleviating lead by
Coronopus didymus from Pb-contaminated soils.
AB - In a screenhouse experiment, we investigated the role of two environment friendly
chelants, Ammonium molybdate and EDDS for Pb mobilisation and its extraction by
Coronopus didymus under completely randomized controlled conditions. Seedlings of
C. didymus were grown in pots having Pb-contaminated soil (1200 and 2200 mg kg-1)
for 6 weeks. Plants were harvested, 1 week after the addition of A. molybdate and
EDDS. Results revealed that A. molybdate and EDDS enhanced the uptake and
accumulation of Pb in roots and shoots of C. didymus. At 2200 mg kg-1 Pb level,
compared to Pb-alone treatment, the maximal concentration of Pb was increased
upto ~10% and ~19%, in roots whereas ~8% and ~18%, respectively, in shoots on
addition of 2 mmol kg-1 A. molybdate and EDDS. Additionally, Pb + EDDS treatments
enhanced the plant biomass and triggered strong antioxidative response, more
efficaciously than Pb + A. molybdate and Pb-alone treated plants. In this study,
EDDS relative to A. molybdate was more efficient in mobilising and extracting Pb
from soil. Although, EDDS followed by A. molybdate had good efficacy in
mitigating Pb from contaminated soils but C. didymus itself has the inherent
affinity to tolerate and accumulate Pb from contaminated soils and hence in
future, can be used either alone or with some other eco-friendly amendments for
soil remediation purposes.
PMID- 28494357
TI - Biosurfactant-producing microorganism Pseudomonas sp. SB assists the
phytoremediation of DDT-contaminated soil by two grass species.
AB - Phytoremediation together with microorganisms may confer the advantages of both
phytoremediation and microbial remediation of soils containing organic
contaminants. In this system biosurfactants produced by Pseudomonas sp. SB may
effectively help to increase the bioavailability of organic pollutants and
thereby enhance their microbial degradation in soil. Plants may enhance the
rhizosphere environment for microorganisms and thus promote the bioremediation of
contaminants. In the present pot experiment study,
dichlorodiphenyltrichloroethane (DDT) residues underwent an apparent decline
after soil bioremediation compared with the original soil. The removal efficiency
of fertilizer + tall fescue, fertilizer + tall fescue + Pseudomonas, fertilizer +
perennial ryegrass, and fertilizer + perennial ryegrass + Pseudomonas treatments
were 59.4, 65.6, 69.0, and 65.9%, respectively, and were generally higher than
that in the fertilizer control (40.3%). Principal coordinates analysis (PCoA)
verifies that plant species greatly affected the soil bacterial community
irrespective of inoculation with Pseudomonas sp. SB. Furthermore, community
composition analysis shows that Proteobacteria, Acidobacteria and Actinobacteria
were the three dominant phyla in all groups. In particular, the relative
abundance of Pseudomonas for fertilizer + tall fescue + Pseudomonas (0.25%) was
significantly greater than fertilizer + tall fescue and this was related to the
DDT removal efficiency.
PMID- 28494358
TI - Herbicide effects on the growth and photosynthetic efficiency of Cassiopea
maremetens.
AB - Herbicides from agricultural run-off have been measured in coastal systems of the
Great Barrier Reef over many years. Non-target herbicide exposure, especially
photosystem II herbicides has the potential to affect seagrasses and other marine
species. The symbiotic benthic jellyfish Cassiopea maremetens is present in
tropical/sub-tropical estuarine and marine environments. Jellyfish (n = 8 per
treatment) were exposed to four separate concentrations of agricultural
formulations of diuron or hexazinone to determine their sensitivity and potential
for recovery to pulsed herbicide exposure. Jellyfish growth, symbiont
photosynthetic activity and zooxanthellae density were analysed for herbicide
induced changes for 7 days followed by a 7 day recovery period. Both the
jellyfish and endosymbiont were more sensitive to diuron than hexazinone. The 7
day EC50 for jellyfish growth was 0.35 MUg L-1 for Diuron and 17.5 MUg L-1 for
Hexazinone respectively. Diuron exposure caused a significant decrease (p < 0.05)
in jellyfish growth at 0.1 MUg L-1, a level that is below the regional Great
Barrier Reef guideline value. Jellyfish recovery was rapid with growth rates
similar to control animals following removal from herbicide exposure. Both diuron
and hexazinone caused significant decreases in photosynthetic efficiency
(effective quantum yield) in all treatment concentrations (0.1 MUg L-1 and above)
and this effect continued in the post-exposure period. As this species is
frequently found in near-shore environments, they may be particularly vulnerable
to herbicide run-off.
PMID- 28494359
TI - Impacts of solids retention time on trace organic compound attenuation and
bacterial resistance to trimethoprim and sulfamethoxazole.
AB - Bacteria can grow in the presence of trimethoprim and sulfamethoxazole by
expressing antibiotic resistance genes or by acquiring thymine or thymidine from
environmental reservoirs to facilitate DNA synthesis. The purpose of this study
was to evaluate whether activated sludge serves as a reservoir for thymine or
thymidine, potentially impacting the quantification of antibiotic resistant
bacteria. This study also assessed the impacts of varying solids retention time
(SRT) on trimethoprim and sulfamethoxazole removal during wastewater treatment
and single and multi-drug resistance. When assayed in the presence of the
antibiotics at standard clinical concentrations, up to 40% increases in the
relative prevalence of resistant bacteria were observed with (1) samples manually
augmented with reagent-grade thymidine, (2) samples manually augmented with
sonicated biomass (i.e., cell lysate), (3) samples manually augmented with
activated sludge filtrate, and (4) activated sludge samples collected from
reactors with longer SRTs. These observations suggest that longer SRTs may select
for antibiotic resistant bacteria and/or result in false positives for antibiotic
resistance due to higher concentrations of free thymine, thymidine, or other
extracellular constituents.
PMID- 28494360
TI - Fluoride induces apoptosis in H9c2 cardiomyocytes via the mitochondrial pathway.
AB - Numerous studies have shown that chronic excessive fluoride intake can adversely
affect different organ systems. In particular, the cardiovascular system is
susceptible to disruption by a high concentration of fluoride. The objectives of
this study were to explore the mechanism of apoptosis by detecting the toxic
effects of different concentrations of sodium fluoride (NaF) in H9c2 cells
exposed for up to 96 h. NaF not only inhibited H9c2 cell proliferation but also
induced apoptosis and morphological damage. With increasing NaF concentrations,
early apoptosis of H9c2 cells was increased while the mitochondrial membrane
potential was decreased. Compared with the control group, the mRNA levels of
caspase-3, caspase-9, and cytochrome c all increased with increasing
concentrations of NaF. In summary, these data suggest that apoptosis is involved
in NaF-induced H9c2 cell toxicity and that activation of the mitochondrial
pathway may occur.
PMID- 28494361
TI - Ferrocene-functionalized graphitic carbon nitride as an enhanced heterogeneous
catalyst of Fenton reaction for degradation of Rhodamine B under visible light
irradiation.
AB - To enhance degradation of Rhodamine B (RhB), a toxic xanthene dye, an iron-doped
graphitic carbon nitride (CN) is prepared by establishing a covalent bond (-CN-)
bridging ferrocene (Fc) and CN via a Schiff base reaction. The pi-conjugation
between the aromatic Fc and CN can be much enhanced by the covalent bond, thereby
facilitating the bulk-to-surface charge transfer and separation as well as
reversible photo-redox reactions during photocatalytic reactions. Thus, the
resulting Fc-CN exhibits a much higher catalytic activity than CN to activate
hydrogen peroxide (HP) for RhB degradation, because the photocatalytically
generated electrons from CN can activate HP and effectively maintain the
bivalence state of Fe in Fc, which also induces the activation of HP. The RhB
degradation by the Fc-CN activated HP process (Fc-CN-HP) is validated to involve
OH* by examining the effect of radical probe agent as well as electron
paramagnetic resonance (EPR) spectroscopic analysis. Fc-CN is also proven to
activate HP for RhB degradation over multiple times without loss of catalytic
activity. Through determining the degradation intermediates, RhB is indeed fully
decomposed by Fc-CN-HP into much lower-molecular-weight organic compounds. These
features indicate that Fc-functionalization can be an advantageous technique to
enhance the catalytic activity of CN for activating HP. The results obtained in
this study are essential to further design and utilize Fc-functionalized CN for
Fenton-like reactions. The findings shown here, especially the degradation
mechanism and pathway, are also quite important for treating xanthene dyes in
wastewater.
PMID- 28494362
TI - Transformation of carbon tetrachloride and chloroform by trichloroethene
respiring anaerobic mixed cultures and supernatant.
AB - Carbon tetrachloride (CT) and chloroform (CF) were transformed in batch reactor
experiments conducted with anaerobic dechlorinating cultures and supernatant (ADC
+ S) harvested from continuous flow reactors. The Evanite (EV) and
Victoria/Stanford (VS) cultures, capable of respiring trichloroethene (TCE), 1,2
cis-dichloroethene (cDCE), and vinyl chloride (VC) to ethene (ETH), were grown in
continuous flow reactors receiving an influent feed of saturated TCE (10 mM; 60
mEq) and formate (45 mM; 90 mEq) but no CT or CF. Cells and supernatant were
harvested from the chemostats and inoculated into batch reactors at the onset of
each experiment. CT transformation was complete following first order kinetics
with CF, DCM and CS2 as the measurable transformation products, representing 20
40% of the original mass of CT, with CO2 likely the unknown transformation
product. CF was transformed to DCM and likely CO2 at an order of magnitude rate
lower than CT, while DCM was not further transformed. An analytical first order
model including multiple key reactions effectively simulated CT transformation,
product formation and transformation, and provided reasonable estimates of
transformation rate coefficients. Biotic and abiotic treatments indicated that CT
was mainly transformed via abiotic processes. However, the presence of live cells
was associated with the transformation of CF to DCM. In biotic tests both TCE and
CT were simultaneously transformed, with TCE transformed to ETH and approximately
15-53% less CF formed via CT transformation. A 14-day exposure to CF (CFmax = 1.4
MUM) reduced all rates of chlorinated ethene respiration by a factor of 10 or
greater.
PMID- 28494363
TI - Reductive solidification/stabilization of chromate in municipal solid waste
incineration fly ash by ascorbic acid and blast furnace slag.
AB - Fly ash is a hazardous byproduct of municipal solid waste incineration (MSWI).
Cementitious material that is based on ground-granulated blast furnace slag
(GGBFS) has been tested and proposed as a binder to stabilize Pb, Cd, and Zn in
MSWI fly ash (FA). Cr, however, still easily leaches from MSWI FA. Different
reagents, such as ascorbic acid (VC), NaAlO2, and trisodium salt nonahydrate,
were investigated as potential Cr stabilizers. The results of the toxicity
characteristic leaching procedure (TCLP) showed that VC significantly improved
the stabilization of Cr via the reduction of Cr(VI) to Cr(III). VC, however,
could interfere with the hydration process. Most available Cr was transformed
into stable Cr forms at the optimum VC content of 2 wt%. Cr leaching was strongly
pH dependent and could be represented by a quintic polynomial model. The results
of X-ray diffraction and scanning electron microscopy-energy dispersive analysis
revealed that hollow spheres in raw FA were partially filled with hydration
products, resulting in the dense and homogeneous microstructure of the solidified
samples. The crystal structures of C-S-H and ettringite retained Zn and Cr ions.
In summary, GGBFS-based cementitious material with the low addition of 2 wt% VC
effectively immobilizes Cr-bearing MSWI FA.
PMID- 28494364
TI - Novel integrated electrodialysis/electro-oxidation process for the efficient
degradation of 2,4-dichlorophenoxyacetic acid.
AB - This work presents a novel approach of wastewater treatment technology that
consists of a combined electrodialysis/electro-oxidation process, specially
designed to allow increasing the efficiency in the oxidation of ionic organic
pollutants contained in diluted waste. Respect to conventional electrolysis, the
pollutant is simultaneously concentrated and oxidized, enhancing the performance
of the cell due to the higher concentration achieved in the nearness of the
anode. A proof of concept is tested with the ionic pesticide 2,4-D (2,4
dichlorophenoxyacetic acid) and results show that the efficiency of this new
technology overcomes that electrolysis by more than double, regardless the
supporting electrolyte used (either NaCl or Na2SO4). Moreover, the removal rate
of 2,4-D when using NaCl was found to be more efficient, due to the best
performance of the electrode material selected (DSA(r)) towards the formation of
oxidants in chloride supporting electrolyte. These results open the way for
overcoming the efficiency limitations of electrochemical treatment processes for
the treatment of solutions with low concentrated ionic pollutants.
PMID- 28494365
TI - A critical review on effects, tolerance mechanisms and management of cadmium in
vegetables.
AB - Cadmium (Cd) accumulation in vegetables is an important environmental issue that
threatens human health globally. Understanding the response of vegetables to Cd
stress and applying management strategies may help to reduce the Cd uptake by
vegetables. The aim of the present review is to summarize the knowledge
concerning the uptake and toxic effects of Cd in vegetables and the different
management strategies to combat Cd stress in vegetables. Leafy vegetables grown
in Cd contaminated soils potentially accumulate higher concentrations of Cd,
posing a threat to food commodities. The Cd toxicity decreases seed germination,
growth, biomass and quality of vegetables. This reduces the photosynthesis,
stomatal conductance and alteration in mineral nutrition. Toxicity of Cd toxicity
also interferes with vegetable biochemistry causing oxidative stress and
resulting in decreased antioxidant enzyme activities. Several management options
have been employed for the reduction of Cd uptake and toxicity in vegetables. The
exogenous application of plant growth regulators, proper mineral nutrition, and
the use of organic and inorganic amendments might be useful for reducing Cd
toxicity in vegetables. The use of low Cd accumulating vegetable cultivars in
conjunction with insolubilizing amendments and proper agricultural practices
might be a useful technique for reducing Cd exposure in the food chain.
PMID- 28494366
TI - Aligned copper nanowires as a cut-and-paste exclusive electrochemical transducer
for free-enzyme highly selective quantification of intracellular hydrogen
peroxide in cisplatin-treated cells.
AB - The role and reliable quantification of intracellular hydrogen peroxide during
cancer therapy constitutes an unexplored and fascinating application. In this
work, we report the fabrication of vertically aligned copper nanowires (v-CuNWs)
using electrosynthesis on templates, and their application as a cut-and-paste
exclusive and flexible electrochemical transducer. This easily adaptable
electrodic platform is demonstrated for a fast, simple and free-enzyme selective
quantification of intracellular hydrogen peroxide in Cisplatin-treated human
renal HK-2 cells. The v-CuNWs sensor was compared with an HRP-enzyme-based
biosensor showing excellent correlation and indicates the good selectivity and
analytical performance of the v-CuNWs. This sensing approach opens novel avenues
for monitoring cell death processes and shows the potential of H2O2 as a cellular
damage biomarker, with a clear potency for further developments for in vitro
diagnosis and its implication in cancer therapy.
PMID- 28494367
TI - Enhanced detection sensitivity of carcinoembryonic antigen on a plasmonic
nanoimmunosensor by transmission grating-based total internal reflection
scattering microscopy.
AB - Carcinoembryonic antigen (CEA) is a glycoprotein associated with colorectal
carcinomas and is commonly used as a clinical tumor marker. Enhanced detection
sensitivity for the assay of CEA molecules was achieved on a plasmonic
nanoimmunosensor by wavelength-dependent transmission grating (TG)-based total
internal reflection scattering microscopy (TIRSM). The plasmonic nanoparticles
were placed in an evanescent field layer on a glass nanoimmunosensor that
produced evanescent wave scattering by the total internal reflection of light
from two lasers. The light scattered by target protein (CEA)-bound 20-nm silver
nanoparticles (plasmonic nanoprobes) was collected and spectrally isolated in
first-order spectral images (n=+1) by a TG (70 grooves/mm). The combination of
evanescent wave scattering and TG significantly enhanced the detection
sensitivity and selectivity due to the minimized spectroscopic interference and
background noise. The TG-TIRSM method detected the CEA molecules at
concentrations down to 19.75zM with a wide linear dynamic range of 19.75zM
39.50nM (correlation coefficient, R=0.9903), which was 45 to 1.25*109 times lower
than the detection limits and 2*105 to 2*1011 times wider than the dynamic ranges
of previous assay methods. In particular, by simply changing the antibody of the
target molecule, this technique can be used to detect various disease-related
protein biomarkers directly in human biological samples at the single-molecule
level.
PMID- 28494368
TI - Metal carbonyl-gold nanoparticle conjugates for highly sensitive SERS detection
of organophosphorus pesticides.
AB - The binding of organometallic osmium carbonyl clusters onto the surface of gold
nanoparticles (10OsCO-Au NPs) greatly enhanced the CO stretching vibration signal
at ~2100cm-1, which is relatively free from interference due to the absorbance of
biomolecules. By utilizing the acetylcholinesterase (AChE) mediated hydrolysis of
acetylthiocholine to thiocholine where the activity of AChE is inhibited by the
presence of organophosphate pesticides (OPPs), the subsequent thiocholine-induced
aggregation of 10OsCO-Au NPs can be monitored by the change in color of the NPs
solution and the variation in intensity of the SERS CO signal. The change in
color offers a fast pre-screening method, whereas monitoring via SERS is used for
greater accuracy and lower limit of detection (0.1 ppb) for quantitative
detection. Its potential as a quick and accurate method of OPPs monitoring in
consumer products was demonstrated in the detection of OPPs in real spiked
samples such as beer.
PMID- 28494370
TI - A novel sensitive sensor for serotonin based on high-quality of AuAg nanoalloy
encapsulated graphene electrocatalyst.
AB - A high quality graphene-encapsulated AuAg alloy (AuAg-GR) nanohybrid with
homogeneous structure and good reproducibility over a desired area was
successfully fabricated. Taking benefits of the unique architecture, such
nanohybrid was employed as an efficient electrocatalyst for sensing application.
The AuAg-GR based sensor could sensitively detected neurotransmitter serotonin (5
HT) with wide linear detection range (2.7nM to 4.82MUM), very low detection limit
(1.6nM), negligible interference, and excellent reproducibility. In addition,
AuAg-GR based sensor accurately determined 5-HT in human serum samples. This is
due to the enhanced catalytic activity of GR nanosheets-encapsulated AuAg
nanostructures, which possessed well monodispersion of AuAg alloy, greater
electrochemical active sites, and good charge transfer possibility. The obtained
results imply that such nanohybrid is a potential candidate for synthesizing
electrochemical sensors in requirement of high sensitivity, long-term stability,
and good reproducibility.
PMID- 28494369
TI - Lateral flow assay-based bacterial detection using engineered cell wall binding
domains of a phage endolysin.
AB - The development of a cost-effective and efficient bacterial detection assay is
essential for diagnostic fields, particularly in resource-poor settings. Although
antibodies have been widely used for bacterial capture, the production of soluble
antibodies is still expensive and time-consuming. Here, we developed a
nitrocellulose-based lateral flow assay using cell wall binding domains (CBDs)
from phage as a recognition element and colloidal gold nanoparticles as a
colorimetric signal for the detection of a model pathogenic bacterium, Bacillus
cereus (B. cereus). To improve conjugation efficiency and detection sensitivity,
cysteine-glutathione-S-transferase-tagged CBDs and maltose-binding protein-tagged
CBDs were produced in Escherichia coli (E. coli) and incorporated in our assays.
The sensitivity of the strip to detect B. cereus was 1*104 CFU/mL and the overall
assay time was 20min. The assay showed superior results compared to the antibody
based approach, and did not show any significant cross-reactivity. This proof of
concept study indicates that the lateral flow assay using engineered CBDs hold
considerable promise as simple, rapid, and cost-effective biosensors for whole
cell detection.
PMID- 28494371
TI - Improving surface EMG burst detection in infrahyoid muscles during swallowing
using digital filters and discrete wavelet analysis.
AB - The visual inspection is a widely used method for evaluating the surface
electromyographic signal (sEMG) during deglutition, a process highly dependent of
the examiners expertise. It is desirable to have a less subjective and automated
technique to improve the onset detection in swallowing related muscles, which
have a low signal-to-noise ratio. In this work, we acquired sEMG measured in
infrahyoid muscles with high baseline noise of ten healthy adults during water
swallowing tasks. Two methods were applied to find the combination of cutoff
frequencies that achieve the most accurate onset detection: discrete wavelet
decomposition based method and fixed steps variations of low and high cutoff
frequencies of a digital bandpass filter. Teager-Kaiser Energy operator, root
mean square and simple threshold method were applied for both techniques. Results
show a narrowing of the effective bandwidth vs. the literature recommended
parameters for sEMG acquisition. Both level 3 decomposition with mother wavelet
db4 and bandpass filter with cutoff frequencies between 130 and 180Hz were
optimal for onset detection in infrahyoid muscles. The proposed methodologies
recognized the onset time with predictive power above 0.95, that is similar to
previous findings but in larger and more superficial muscles in limbs.
PMID- 28494372
TI - Separation and preconcentration of riboflavin from human plasma using
polythionine coated magnetite/hydroxyapatite nanocomposite prior to analysis by
surfactant-enhanced fluorimetry.
AB - The exploration of novel adsorption properties of conductive polymers based on
hybridization with biocompatible nanomaterials receives an increasing interest.
In this regard, hydroxyapatite (HA) bioceramic is of critical importance mainly
owing to its facile synthesis, high surface area, economic and low toxicity in
biological environments. In this work, we first prepared and characterized a
magnetite/hydroxyapatite (Fe3O4/HA) nanocomposite using the bio-waste chicken
eggshell via an attractive green way that involved low cost and irrespective of
toxicity. Then, polythionine as a novel class of conductive polymers was in situ
coated on the synthesized magnetic bioceramic for the separation and
preconcentration of riboflavin (vitamin B2) in human plasma before its
fluorimetric determination. Considering the putative role of riboflavin in
protecting against cancer and cardiovascular diseases, it is essential to
evaluate this vitamin in biological fluids. The described method possesses a
linear range of 0.75-262.5MUgL-1 (R2=0.9985) and a detection limit of 0.20MUgL-1
(signal-to-noise ratio of 3). The relative standard deviations (RSDs) for single
sorbent repeatability and sorbent-to-sorbent reproducibility were less than 4.0%
and 7.6% (n=5), respectively. The respective enrichment factor and extraction
recovery of the method found to be 35.7 and 98.4%. The analytical performance of
method for riboflavin was characterized by good consistency of the results with
those obtained by the enzyme-linked immunosorbent assay (ELISA) conventional
method (p-value of <0.05). The optimized protocol intended for control
determinations of riboflavin in human subjects and is addressed to clinical
laboratories.
PMID- 28494373
TI - Influence of Li+ charge compensator ion on the energy transfer from Pr3+ to Gd3+
ions in Ca9Mg(PO4)6F2:Gd3+, Pr3+, Li+ phosphor.
AB - Phototherapy is a renowned treatment for curing skin diseases since ancient
times. Phototherapeutic treatment for psoriasis and many other diseases require
narrow band ultra violet-B (NB-UVB) light with peak intensity at 313nm to be
exposed to the affected part of body. In this paper, we report combustion
synthesis of NB-UVB -313nm emitting Ca9Mg(PO4)6F2 phosphors doped with Gd3+, Pr3+
and Li+ ions. The phase formation was confirmed by obtaining X-ray diffraction
(XRD) pattern and morphology was studied with the Scanning electron microscopy
(SEM) images. Photoluminescence (PL) emission spectra show intense narrow band
emission at 313nm under 274nm excitation wavelengths. Emission intensity was
enhanced when Ca9Mg(PO4)6F2 compound is co-doped with Pr3+ ions. Excitation
spectra of Ca9Mg(PO4)6F2:Gd3+, Pr3+ doped samples shows broad excitation in ultra
violet C (UVC) region. Diffuse reflectance spectra (DRS), obtained by UV-visible
spectrophotometer, measures the absorption properties of the material. By
applying Kubelka Munk function on the diffuse reflectance spectra, band gap of
the material is determined. PL decay curves were examined which indicates
efficient energy transfer between Pr3+ and Gd3+ ions. Charge compensation effect
was also studied by co-doping Li+ ion in host. Emission intensity was found to
increase with the addition of charge compensator. The prepared phosphor has
potential to convert UVC light into NB-UVB. The luminescence intensity of Gd3+
shows remarkable increase when it is sensitized with Pr3+, and an addition of
charge compensator in the form of Li+, show even better results. This phosphor
surely has the potential to be used as phototherapy lamp phosphor.
PMID- 28494374
TI - Eigenvalue-eigenvector decomposition (EED) analysis of dissimilarity and
covariance matrix obtained from total synchronous fluorescence spectral (TSFS)
data sets of herbal preparations: Optimizing the classification approach.
AB - The present work compares the dissimilarity and covariance based unsupervised
chemometric classification approaches by taking the total synchronous
fluorescence spectroscopy data sets acquired for the cumin and non-cumin based
herbal preparations. The conventional decomposition method involves eigenvalue
eigenvector analysis of the covariance of the data set and finds the factors that
can explain the overall major sources of variation present in the data set. The
conventional approach does this irrespective of the fact that the samples belong
to intrinsically different groups and hence leads to poor class separation. The
present work shows that classification of such samples can be optimized by
performing the eigenvalue-eigenvector decomposition on the pair-wise
dissimilarity matrix.
PMID- 28494375
TI - Thin film assembly of nanosized cobalt(II) bis(5-phenyl-azo-8-hydroxyquinolate)
using static step-by-step soft surface reaction technique: Structural
characterization and optical properties.
AB - Nanosized (NS) cobalt (II) bis(5-phenyl-azo-8-hydroxyquinolate) (NS Co(II)-(5PA
8HQ)2) thin films have been synthesized using static step-by-step soft surface
reaction (SS-b-SSR) technique. Structural and optical characterizations of these
thin films have been carried out using thermal gravimetric analysis (TGA),
Fourier transform infrared (FT-IR), scanning electron microscopy (SEM), high
resolution transmission electron microscopy (HR-TEM) and X-ray diffraction (XRD).
The HR-TEM results revealed that the assembled Co(II)-complex exhibited a
uniformly NS structure particles in the form of nanorods with width and length up
to 16.90nm and 506.38nm, respectively. The linear and nonlinear optical
properties have been investigated. The identified energy gap of the designed thin
film materials was found 4.01eV. The refractive index of deposited Co(II)-complex
thin film was identified by thickness-dependence and found as 1.9 at wavelength
1100nm. In addition, the refractive index was varied by about 0.15 due to an
increase in the thickness by 19nm.
PMID- 28494376
TI - Luminescent properties of heterotrinuclear 3d-4f complexes constructed from a
naphthalenediol-based acyclic bis(salamo)-type ligand.
AB - Heterotrinuclear 3d-4f complexes with a naphthalenediol-based acyclic bis(salamo)
type ligand have been synthesized and structurally characterized. Spectral
titrations clearly show that the heterotrinuclear complexes [Zn2(L)La(OAc)3] (1),
[Zn2(L)Ce(OAc)3] (2) and [Zn2(L)Dy(OAc)3(CH3OH)].CH2Cl2 (3) are acquired by the
substitution reaction of the obtained homotrinuclear Zn(II) complex with 1 equiv.
of Ln(NO3)3 (Ln3+=La3+, Ce3+ and Dy3+). Two Zn(II) ions are penta- and hexa
coordinated with geometries of distorted tetragonal pyramid and octahedron.
La(III) ion is deca-coordinated, adopting a distorted bicapped square antiprism
geometry. Ce(III) ion is nona-coordinated with geometry of distorted capped
square antiprism as well as Dy(III) ion. The different coordination modes of
acetate ions in complexes 1, 2 and 3 lead to different coordination numbers of
the lanthanide(III) ions. Furthermore, the structures and fluorescence properties
have been discussed.
PMID- 28494377
TI - Preparation and characterization of electrodeposited SnS:In thin films: Effect of
In dopant.
AB - SnS:In thin films were grown on fluorine doped tin oxide (FTO) substrate by
cathodic electrodeposition technique. The solution was containing 2mM SnCl2 and
16mM Na2S2O3 and different amounts of 1mM InCl3 as In-dopant. The pH, bath
temperature, deposition time, and deposition potential (E) were fixed at 2.1, 60
degrees C, 30min, and -1V, respectively. The XRD results showed that the
synthesized films were polycrystalline orthorhombic SnS. The XPS results
demonstrated that the films were composed of Sn, S and In. According to the FESEM
images, an increase in In-dopant concentration leads to a change in morphology
from grain-like to sheet-like having a nanoscale thickness of 20-80nm and fiber
like. The PL spectra of undoped SnS exhibited four emission peaks including a UV
peak, two blue emission peaks, and an IR emission peak. According to the UV-Vis
spectra, the direct band gap of SnS:In thin films was estimated to be 1.40
1.66eV.
PMID- 28494378
TI - FTIR cryospectroscopic and ab initio studies of desflurane-dimethyl ether H
bonded complexes.
AB - The IR spectra of mixtures of desflurane and dimethyl ether are studied with the
help of FTIR cryospectroscopy in liquefied Kr at T~118-158K. Comparative analysis
of the experimental data and results of ab initio calculations show that either
of the two C-H groups of desflurane is involved in heterodimer formation of
comparable strengths. The blue frequency shift is found for stretching vibrations
of those C-H donors which directly participate in H-bond formation. Additionally
the complexes are stabilized by weaker contacts between hydrogen atoms of
dimethyl ether and fluorine atoms of desflurane.
PMID- 28494379
TI - Study on molecular structure, spectroscopic properties (FTIR and UV-Vis), NBO,
QTAIM, HOMO-LUMO energies and docking studies of 5-fluorouracil, a substance used
to treat cancer.
AB - Cancer cells can expand to other parts of body through blood system and nodes
from a mechanism known as metastasis. Due to the large annual growth of cancer
cases, various biological targets have been studied and related to this disorder.
A very interesting target related to cancer is human epidermal growth factor
receptor 2 (HER2). In this study, we analyzed the main intermolecular
interactions between a drug used in the cancer treatment (5-fluorouracil) and
HER2. Molecular modeling methods were also employed to assess the molecular
structure, spectroscopic properties (FTIR and UV-Vis), NBO, QTAIM and HOMO-LUMO
energies of 5-FU. From the docking simulations it was possible to analyze the
interactions that occur between some residues in the binding site of HER2 and 5
FU. To validate the choice of basis set that was used in the NBO and QTAIM
analyses, theoretical calculations were performed to obtain FT-IR and UV/Vis
spectra, and the theoretical results are consistent with the experimental data,
showing that the basis set chosen is suitable. For the maximum lambda from the
theoretical calculation (254.89nm) of UV/Vis, the electronic transition from HOMO
to LUMO occurs at 4.89eV. From NBO analyses, we observed interactions between
Asp863 and 5-FU, i.e. the orbitals with high transfer of electrons are LP O15
(donor NBO) and BD* (pi) N1-H10 (acceptor NBO), being that the value of this
interaction is 7.72kcal/mol. Results from QTAIM indicate one main intermolecular
H bond, which is necessary to stabilize the complex formed between the ligands
and the biological target. Therefore, this study allowed a careful evaluation on
the main structural, spectroscopic and electronic properties involved in the
interaction between 5-FU and HER2, an important biological complex related to the
cancer treatment.
PMID- 28494380
TI - A highly sensitive turn-on fluorescent chemosensor for recognition of Zn2+ and
Hg2+ and applications.
AB - A fluorescence probe has been designed and synthesized, and applied with a
combined theoretical and experimental study. Research suggests that the probe can
be used to sense Zn2+ and Hg2+ through selective turn-on fluorescence responses
in the aqueous HEPES buffer (0.05M, pH=7.4). The limit of detection (LOD) were
determined as 1.46*10-7M (Zn2+) and 2.50*10-7M (Hg2+). Moreover, based on DFT,
the geometry optimizations of probe 1, [1-Hg2+] complex and [1-Zn2+] complex were
carried out using the Gaussian 09 program, in which the B3LYP function was used.
The electronic properties of free probe 1 and the metal complexes were studied
based on the Natural Bond Orbital (NBO) analyses. The probe 1 has also been
successfully applied to detection of Zn2+ and Hg2+ in living cells.
PMID- 28494381
TI - Spectroscopic analysis of hot-water- and dilute-acid-extracted hardwood and
softwood chips.
AB - Hot-water and dilute sulfuric acid pretreatments were performed prior to chemical
pulping for silver/white birch (Betula pendula/B. pubescens) and Scots pine
(Pinus sylvestris) chips to determine if varying pretreatment conditions on the
original wood material were detectable via attenuated total reflectance (ATR)
infrared spectroscopy. Pretreatment conditions varied with respect to temperature
(130 degrees C and 150 degrees C) and treatment time (from 30min to 120min). The
effects of the pretreatments on the composition of wood chips were determined by
ATR infrared spectroscopy. The spectral data were compared to those determined by
common wood chemistry analyses to evaluate the suitability of ATR spectroscopy
method for rapid detection of changes in the wood chemical composition caused by
different pretreatment conditions. In addition to determining wood species
dependent differences in the wood chemical composition, analytical results
indicated that most essential lignin- and carbohydrates-related phenomena taking
place during hot-water and acidic pretreatments could be described by applying
this simple spectral method requiring only a small sample amount and sample
preparation. Such information included, for example, the cleavage of essential
lignin bonds (i.e., mainly beta-O-4 linkages in guaiacyl and syringyl lignin) and
formation of newly condensed lignin structures under different pretreatment
conditions. Carbohydrate analyses indicated significant removal of hemicelluloses
(especially hardwood xylan) and hemicelluloses-derived acetyl groups during the
pretreatments, but they also confirmed the highly resistant nature of cellulose
towards mild pretreatments.
PMID- 28494382
TI - A computer-supported management of photographic documentation in plastic surgery
System development and its clinical application.
AB - Photographic documentation is very important for plastic, reconstructive, and
especially aesthetic surgery procedures. It can be used to improve patient care
as well as to carry out scientific research. The results of our previous studies
confirmed a strong demand for Information Technology (IT) systems dedicated to
plastic surgery. Unfortunately, most of the solutions of this type are not suited
to the actual needs. For this reason we decided to develop a reliable system for
photographic documentation storage. The Plastic Reconstructive Esthetic Surgery
Photo System (PRESsPhoto) was developed and finally deployed in the Plastic,
Reconstructive and Aesthetic Surgery Clinic of the Medical University in Lodz
(Poland). Preliminary single-center performance tests proved that the PRESsPhoto
system is easy to use and provides, inter alia, rapid data search and data entry
as well as data security. In the future the PRESsPhoto system should be able to
cooperate with Hospital Information Systems (HIS). The process of development and
deployment of the PRESsPhoto system is an example of good cooperation between
health care providers and the informatics, which resulted in a system that meets
the expectations of plastic surgeons.
PMID- 28494383
TI - A robust construction algorithm of the centerline skeleton for complex aortic
vascular structure using computational fluid dynamics.
AB - Centerlines of blood vessels are useful tools to make important anatomical
measurements (length, diameter, area), which cannot be accurately obtained using
2D images. In this paper a brand new method for centerline extraction of vascular
trees is presented. By using computational fluid dynamics (CFD) we are able to
obtain a robust and purely functional centerline allowing us to support better
measurements than classic purely geometrical-based centerlines. We show that the
CFD-based centerline is within a few pixels from the geometrical centerline where
the latter is defined (far away from inlet/outlets and from the branches). We
show that the centerline computed with our method is not affected by traditional
errors of other classical volume-based algorithms such as topological thinning,
and could be a potential alternative to be considered for future studies.
PMID- 28494384
TI - Attentional blink to alcohol cues in binge drinkers versus non-binge drinkers.
AB - Previous studies have shown alcohol-related attentional biases in social
drinkers; however, the temporal dynamics of these biases are not well understood.
The current study examined this issue in 94 participants (27 male) categorized as
binge drinkers (BD) or non-binge drinkers (NBD). Two versions of an alcohol
related attentional blink (AB) paradigm were used: one with words and one with
images. It was predicted that BDs (versus NBDs) would exhibit reduced AB for
alcohol cues, which would be enhanced for the pictorial version of the task
(versus words). The relationships between AB and alcohol craving, quantity and
frequency of alcohol consumption, symptoms of alcohol use disorder, and family
history of alcohol use disorder (AUD) were also examined. While an AB was
observed for both alcohol and non-alcohol targets in the NBD group, no AB was
found for alcohol targets in the BD group. Furthermore, the magnitude of the AB
was related to drinking, such that higher self-reported hazardous drinking was
associated with smaller ABs to alcohol-related targets. However, AB was not
related to craving or family history of AUD. These results suggest that alcohol
related stimuli are processed more efficiently by BDs, especially those with
hazardous alcohol consumption patterns. These results may inform treatment and
prevention efforts targeting binge drinkers.
PMID- 28494385
TI - L-leucine dietary supplementation modulates muscle protein degradation and
increases pro-inflammatory cytokines in tumour-bearing rats.
AB - Cancer cachexia is characterised by involuntary weight loss associated with
systemic inflammation and metabolic changes. Studies aimed at maintaining lean
body mass in cachectic tumour-bearing hosts have made important contributions
reducing the number of deaths and improving the quality of life. In recent years,
leucine has demonstrated effective action in maintaining lean body mass by
decreasing muscle protein degradation. Currently, there is a growing need to
understand how leucine stimulates protein synthesis and acts protectively in a
cachectic organism. Thus, this study aimed to assess the effects of a leucine
rich diet on protein degradation signalling in muscle over the course of tumour
growth. Animals were distributed into four experimental groups, which did or did
not receive 2*106 viable Walker-tumour cells. Some were fed a leucine-rich diet,
and the groups were subsequently sacrificed at three different time points of
tumour evolution (7th, 14th, and 21st days). Protein degradation signals, as
indicated by ubiquitin-proteasome subunits (11S, 19S, and 20S) and pro- and anti
inflammatory cytokines, were analysed in all experimental groups. In tumour
bearing animals without nutritional supplementation (W7, W14, and W21 groups), we
observed that the tumour growth promoted a concurrent decrease in muscle protein,
a sharp increase in pro-inflammatory cytokines (TNFalpha, IL-6, and IFNgamma),
and a progressive increase in proteasome subunits (19S and 20S). Thus, the
leucine-supplemented tumour-bearing groups showed improvements in muscle mass and
protein content, and in this specific situation, the leucine-rich diet led to an
increase on the day in cytokine profile and proteasome subunits mainly on the
14th day, which subsequently had a modulating effect on tumour growth on the 21st
day. These results indicate that the presence of leucine in the diet may modulate
important aspects of the proteasomal pathway in cancer cachexia and may prevent
muscle wasting due to the decrease in the cachexia index.
PMID- 28494386
TI - Effect of efferent activation on binaural frequency selectivity.
AB - Binaural notched-noise experiments indicate a reduced frequency selectivity of
the binaural system compared to monaural processing. The present study
investigates how auditory efferent activation (via the medial olivocochlear
system) affects binaural frequency selectivity in normal-hearing listeners.
Thresholds were measured for a 1-kHz signal embedded in a diotic notched-noise
masker for various notch widths. The signal was either presented in phase
(diotic) or in antiphase (dichotic), gated with the noise. Stimulus duration was
25 ms, in order to avoid efferent activation due to the masker or the signal. A
bandpass-filtered noise precursor was presented prior to the masker and signal
stimuli to activate the efferent system. The silent interval between the
precursor and the masker-signal complex was 50 ms. For comparison, thresholds for
detectability of the masked signal were also measured in a baseline condition
without the precursor and, in addition, without the masker. On average, the
results of the baseline condition indicate an effectively wider binaural filter,
as expected. For both signal phases, the addition of the precursor results in
effectively wider filters, which is in agreement with the hypothesis that
cochlear gain is reduced due to the presence of the precursor.
PMID- 28494387
TI - A review of sociocultural factors that may underlie differences in African
American and European American anxiety.
AB - Preliminary evidence indicates there may be differences in the prevalence and
severity of anxiety in African Americans and European Americans. A number of
sociocultural risk and protective factors have been suggested to contribute to
these group differences, such as salience of physical illnesses, discrimination,
stigma toward mental illness, religiosity, and ethnic identity. In this paper,
the literature concerning each of these factors is reviewed. Overall, the
strongest evidence was found for ethnic identity and stigma toward mental illness
as factors underlying group differences in anxiety. Ethnic identity and stigma
toward mental illness consistently differed by racial group and were associated
with anxiety in African Americans. Ethnic identity may buffer against the
negative consequences of anxiety, reducing prevalence rates in African Americans.
Stigma toward mental illness may decrease African Americans willingness to report
anxiety symptoms, reducing overall prevalence rates but increasing the severity
of treated cases. The research regarding discrimination, salience of physical
illnesses, and religiosity was less clear. Much more research is required, but
the findings of this review suggest that future studies should put particular
emphasis on stigma toward mental illness and ethnic identity as important factors
in understanding African American anxiety outcomes.
PMID- 28494388
TI - Skills-based childbirth preparation reduces stress for midwives.
AB - OBJECTIVE: to explore the potential benefits of skills-based childbirth
preparation on the work related stress levels of midwives. DESIGN: a
questionnaire was sent out to midwives who had clients participating in an RCT of
an education package for childbirth preparation (The Pink Kit (PK) Method for
Birthing Better(r)) delivered to parents. SETTING: midwives were in private
practice and acted as lead maternity carers to New Zealand first time mothers.
PARTICIPANTS: one hundred and four independent midwives participated.
MEASUREMENTS: a brief questionnaire using a Visual Analogue Scale to portray
perceptions of work-related stress and a yes/no question about expected and/or
unexpected physical complications. FINDINGS: midwives working with clients in the
intervention group experienced less work-related stress after correction for
medical complications compared to the two control groups. KEY CONCLUSIONS:
working with mothers who have used a programme that increased their childbirth
self-efficacy decreased the work-related stress experienced by midwives.
IMPLICATIONS FOR PRACTICE: encouraging pregnant women to develop childbirth
skills merits further investigation in an effort to reduce the work-related
stress experienced by midwives.
PMID- 28494389
TI - Breastfeeding support and opiate dependence: A think aloud study.
AB - OBJECTIVE: international guidelines recommend the promotion and protection of
breastfeeding for the substance exposed mother and baby. Yet few studies have
explored the facilitators, moderators and barriers to successful breastfeeding
for women enrolled on opiate maintenance treatment, or suggested targeted support
strategies. The aim of this study was to explore the views of women with opiate
dependence on proposed elements for inclusion in a breastfeeding support
intervention. DESIGN: a qualitative study using think aloud technique. SETTING:
tertiary maternity hospital in the North-East of Scotland. Interviews conducted
between November 2013 and March 2014. PARTICIPANTS: 6 opiate dependent women
within 6 months of giving birth. Participants were enrolled on opiate medication
treatment during their pregnancy, had initiated breastfeeding and accessed in
hospital breastfeeding support. FINDINGS: an intervention founded on practical,
informational and environmental elements was endorsed as supportive of continued
breastfeeding of an infant at risk of Neonatal Abstinence Syndrome. Opiate
dependent women were more receptive to strategies promoting a person-centered
approach that were specific to their individualized infant feeding needs and
delivered within an emotionally supportive environment. Barriers to the
acceptability of breastfeeding advice included discouraging, prescriptive and
judgemental healthcare actions and attitudes. KEY CONCLUSIONS: there are distinct
facilitators, modifiers and barriers to breastfeeding within the context of
opiate exposure. Using this awareness to underpin the key features of the design
should enhance maternal receptiveness, acceptability and usability of the support
intervention. IMPLICATIONS FOR PRACTICE: additional and tailored support
interventions are required to meet the specific needs of breastfeeding an infant
experiencing opiate withdrawal. The elimination of disempowering institutional
actions and attitudes is imperative if a conducive environment in which opiate
dependent women feel supported is to be achieved.
PMID- 28494390
TI - Bipolar patients treated with long-acting injectable risperidone in Taiwan: A 1
year mirror-image study using a national claims database.
AB - OBJECTIVE: Bipolar disorder (BD) is burdensome for patients and healthcare
systems. This study evaluated changes in concomitant medication patterns,
healthcare utilization, and costs after the initiation of risperidone long-acting
injection (RLAI) treatment among BD patients. METHOD: 287 BD patients receiving
regular RLAI treatment for 1 year were identified from the Taiwan National Health
Insurance Research database during 2007-2012. The bootstrapping procedure was
performed to create 1000 samples to generate normally distributed data. The
paired t-tests with a correction for multiple comparisons using Bonferroni
correction were used to compare the proportion of patients of concomitant
psychiatric medication and resource use and costs between pre- and post-RLAI
periods. Rapid and non-rapid cycling stratification was performed based on the
number of change-in-mood episodes within 1 year prior to the index date. RESULTS:
The mean annual dose of RLAI was 638.41mg, which was equal to an average dose of
24.6mg every 2 weeks. The prevalence of concomitant use of conventional
antipsychotics, atypical antipsychotics, lithium, and antidepressants decreased
from the pre-RLAI period to the post-RLAI period by 23.75%, 31.91%, 1.29%, and
7.08%, respectively. RLAI use decreased emergency room (ER) visits, hospital
admissions, length of hospital stay, and non-medication costs (all P<0.0001). The
cost savings with RLAI were attributed to lower hospitalization costs in spite of
higher medication costs. Moreover, rapid cycling patients (n=36) demonstrated
greater reduction in ER and inpatient services with RLAI than non-rapid cycling
patients (n=251). LIMITATIONS: Of the patients who initiated RLAI, 15% of them
who had regular treatment were included. Furthermore, data on measures of symptom
severity, side effects, and hyperprolactinemia were not available. CONCLUSION: BD
patients had lower inpatient and ER utilization, and non-medication costs after
using RLAI. In addition, RLAI use decreased the number of change-in-mood episodes
in rapid cycling patients; which provides additional insights into the treatment
of rapid cycling BD patients.
PMID- 28494391
TI - Living with parents or with parents-in-law and postpartum depression: A
preliminary investigation in China.
AB - BACKGROUND: Few studies have investigated the association between puerperal
women's living situation and postpartum depression. The aim of this study was to
examine the association between living with parents or with parents-in-law and
postpartum depression among Chinese puerperal women. METHODS: A total of 1126
participants who completed questionnaire were included in our analysis.
Postpartum depression status was assessed using the Edinburgh Postnatal
Depression Scale. Logistic regression models were used to estimate the
association between living with puerperal women's parents or with parents-in-law
and risk of postpartum depression after adjustment for potential confounders.
RESULTS: The prevalence of postpartum depression among participants was 11.8%. Of
the 1126 participants, 524 (46.5%) lived only with their husbands, 387 (34.4%)
lived with their parents-in-law, and 215 (19.1%) lived with their parents.
Compared with those living only with their husbands, puerperal women living with
their parents-in-law had higher risk of postpartum depression after adjustment
for potential confounders (OR=2.48; 95% CI: 1.20, 5.15). No association between
living with puerperal women's parents and postpartum depression was found after
adjustment for confounders (OR=1.05; 95%CI: 0.42, 2.65). LIMITATIONS: Although we
adjusted for a wide range of potential confounders, we cannot rule out the
possibility of residual confounding by other unmeasured factors, such as
breastfeeding, intimate partner violence, and marital relationship. CONCLUSIONS:
Our findings suggest that living with parents-in-law may be a risk factor for
postpartum depression among Chinese puerperal women. Future preventive
interventions should include strategies that target the puerperal women who lived
with parents-in-law.
PMID- 28494392
TI - Opposed effects of hyperthymic and cyclothymic temperament in substance use
disorder (heroin- or alcohol-dependent patients).
AB - INTRODUCTION: In the last decade, the comprehension of affective temperaments has
helped us to outline the boundaries of mood disorders, and to expand our
knowledge of nosographic areas other than those of affectivity, even if
affectivity is closely related to them. In the field of substance use disorders,
the temperamental profile of heroin addicts and alcoholics has been discussed
elsewhere, but no comparison has yet been made between these two patient
populations. Such a comparison would help to shed light on the pathogenetic
mechanisms that link temperament with substance abuse. METHODS: 63 Heroin Use
Disorder (HUD) and 94 Alcohol Use Disorder (AUD) patients were compared with 130
healthy controls, with the aim of outlining affective temperament quantity and
typology according to the formulation of Akiskal and Mallya. RESULTS: Cyclothymic
temperamental quantity differentiated - both at the univariate and multivariate
levels - between patients who had various different types of Substance Use
Disorder, largely irrespective of the principal substance of abuse (heroin or
alcohol); irritable temperament quantity differentiated HUD patients from AUD
patients. Hyperthymic temperament typology seemed to be more frequent in healthy
controls at both univariate and multivariate levels. LIMITATION: Cross-sectional
study. CONCLUSIONS: Our analyses suggest that cyclothymic temperament quantity
could best correspond to the temperamental profile of Substance Use Disorder
patients independently of principal substance of abuse (alcohol or heroin), and
that irritable temperament quantity may differentiate HUD from AUD patients.
Hyperthymic temperament typology seemed to be highly protective for HUD and,
though a bit less, for AUD patients, and was a typical feature of healthy
controls.
PMID- 28494393
TI - Alterations in growth, oxidative damage, and metal uptake of five aromatic rice
cultivars under lead toxicity.
AB - Lead (Pb) affects plant growth and its related physio-biochemical functions
negatively. The present study investigated the responses of five different
fragrant rice cultivars viz., Meixiangzhan (MXZ-2), Xiangyaxiangzhan (XYXZ),
Guixiangzhan (GXZ), Basmati-385 (B-385), and Nongxiang-18 (NX-18) to four
different Pb concentrations viz., 0, 400, 800 and 1200 MUM. Results depicted that
Pb toxicity significantly (P < 0.05) reduced the plant height, tillering ability
and biomass accumulation by causing oxidative damage to rice plants; nonetheless,
a significant variation was found in the sensitivity of rice cultivars to Pb
toxicity. Soluble sugars increased significantly only at 1200 MUM in GXZ and 800
MUM in B-385, whilst the maximum reductions in protein contents were observed at
1200 MUM Pb for all rice cultivars. Proline contents were reduced for XYXZ and NX
18 at Pb1200 MUM. Activities of superoxide dismutase (SOD), peroxidase (POD),
catalase (CAT) and ascorbate peroxidase (APX) as well as reduced glutathione
(GSH) and oxidized glutathione (GSSG) showed differential behavior among Pb
treatments and rice cultivars. Among rice cultivars, GXZ showed better
antioxidative defense system under Pb toxicity compared with all other cultivars.
For all rice cultivars, the trend for Pb accumulation was recorded as: roots >
stems > leaves. Furthermore, significant but negative correlations among Pb
uptake and plant height (r = -0.79), tillers per plant (r = -0.91) and plant dry
biomass (r = -0.81) were recorded for all rice cultivars whereas the values of
translocation factor (TF) from stems to leaves were higher than roots to stems.
In sum, Pb reduced the early growth and caused physio-biochemical changes in all
rice cultivars, nonetheless, GXZ proved better able to tolerate Pb stress than
all other rice cultivars under study.
PMID- 28494394
TI - Physiological and biochemical changes attenuate the effects of drought on the
Cerrado species Vatairea macrocarpa (Benth.) Ducke.
AB - Drought is considered the main abiotic stress because it influences the
distribution of plant species and limits the productivity of ecosystems. The aim
of this study was to evaluate the effects of drought on physiological and
biochemical parameters during the initial development of Vatairea macrocarpa, a
native cerrado species. Plants were subjected to daily watering (control);
suppression of watering during 90 days with field capacity (fc) 50% and 25% and
then followed by rewatering. Relative leaf water content (RWC), gas exchange,
photosynthetic pigments content, carbohydrate and amino acids content,
antioxidant activities and growth were recorded. The RWC decreased according to
the soil water restriction, causing reduction in stomatal conductance and
decrease of 76.4% in net photosynthesis in plants submitted to 25% fc. Water
restriction decreased the chlorophyll content, however increased carotenoid
content and also improved the antioxidant activities of superoxide dismutase
(SOD), ascorbate peroxidase (APX) and catalase (CAT). In addition, high levels of
sugars (sucrose, raffinose) and amino acids (proline, tryptophan, valine,
glutamine and GABA) were detected in drought stressed plants, contributing to
osmoregulation and as sources of carbon and nitrogen after rehydration. Decreases
in carbon assimilation promoted a reduction of the leaf area, however an increase
in the root surface area was observed. After rewatering, the analized parameters
became similar to the control plants indicating that the severe water stress did
not impair the survival of young plants. Instead, adjustments were made to
protect them against drought such as the maintenance of the assimilatory
metabolism at minimal levels.
PMID- 28494395
TI - Conformational and vibrational reassessment of solid paracetamol.
AB - This work provides an answer to the urge for a more detailed and accurate
knowledge of the vibrational spectrum of the widely used analgesic/antipyretic
drug commonly known as paracetamol. A comprehensive spectroscopic analysis -
including infrared, Raman, and inelastic neutron scattering (INS) - is combined
with a computational approach which takes account for the effects of
intermolecular interactions in the solid state. This allows a full reassessment
of the vibrational assignments for Paracetamol, thus preventing the propagation
of incorrect data analysis and misassignments already found in the literature. In
particular, the vibrational modes involving the hydrogen-bonded NH and OH groups
are correctly reallocated to bands shifted by up to 300cm-1 relatively to
previous assignments.
PMID- 28494396
TI - A comparative study of the spectral, fluorometric properties and photostability
of natural curcumin, iron- and boron- complexed curcumin.
AB - Curcumin is a yellow phenolic compound with a wide range of reported biological
effects. However, two main obstacles hinder the use of curcumin therapeutically,
namely its poor bioavailability and photostability. We have synthesized two
curcumin complexes, the first a boron curcumin complex (B-Cur2) and the second an
iron (Fe-Cur3) complex of curcumin. Both derivatives showed high fluorescence
efficiency (quantum yield) and greater photostability in solution. The improved
photostability could be attributed to the coordination structures and the removal
of beta-diketone group from curcumin. The fluorescence and ultra violet/visible
absorption spectra of curcumin, B-Cur2 and Fe-Cur3 all have a similar spectral
pattern when dissolved in the same organic solvent. However, a shift towards a
lower wavelength was observed when moving from polar to non-polar solvents,
possibly due to differences in solvent polarity. A plot of Stokes' shift vs the
orientation polarity parameter (Deltaf) or vs the solvent polarity parameter (ET
30) showed an improved correlation between the solvent polarity parameter than
with the orientation polarity parameter and indicating that the red shift
observed could be due to hydrogen-bonding between the solvent molecules. A
similar association was obtained when Stokes' shift was replaced by maximum
synchronous fluorescence. Both B-Cur2 and Fe-Cur3 had larger quantum yields than
curcumin, suggesting they may be good candidates for medical imaging and in vitro
studies.
PMID- 28494397
TI - Bioaccumulation and elimination of bisphenol a (BPA) in the alga Chlorella
pyrenoidosa and the potential for trophic transfer to the rotifer Brachionus
calyciflorus.
AB - In this study, we investigated the bioaccumulation and elimination of 14C-labeled
BPA by the green alga Chlorella pyrenoidosa and the subsequent transfer of 14C
BPA residues from the contaminated alga to the rotifer Brachionus calyciflorus.
After 10 days of BPA exposure, the algal cells accumulated 15% of the initial
radioactivity from the medium, with 71% of the accumulated radioactivity
occurring in the form of non-extractable bound residues. An approximate steady
state of the accumulation of the 14C-BPA residues in the algae was reached after
about 4 days of exposure. The bioconcentration factor of total radioactivity in
the algae was 106 mL (g dry weight)-1 at steady state. During the elimination
phase, only the extractable residues were released from the algae into the water
whereas the bound residues, following their ingestion by the rotifers, were
converted to extractable forms and then also released. Furthermore, our results
demonstrated the biomagnification of BPA-related residues in the food chain
between algae and rotifers. The trophic transfer of these BPA-derived residues
from the algae to rotifers and thus the environmental hazard may posed by this
pathway, because of subsequent effects on the food chain.
PMID- 28494398
TI - Oil uptake by plant-based sorbents and its biodegradation by their naturally
associated microorganisms.
AB - The plant waste-products, wheat straw, corn-cobs and sugarcane bagasse took up
respectively, 190, 110 and 250% of their own weights crude oil. The same
materials harbored respectively, 3.6 * 105, 8.5 * 103 and 2.3 * 106 g-1 cells of
hydrocarbonoclastic microorganisms, as determined by a culture-dependent method.
The molecular, culture-independent analysis revealed that the three materials
were associated with microbial communities comprising genera known for their
hydrocarbonoclastic activity. In bench-scale experiments, inoculating oily media
with samples of the individual waste products led to the biodegradation of 34.0
44.9% of the available oil after 8 months. Also plant-product samples, which had
been used as oil sorbents lost 24.3-47.7% of their oil via their associated
microorganisms, when kept moist for 8 months. In this way, it is easy to see that
those waste products are capable of remediating spilled oil physically, and that
their associated microbial communities can degrade it biologically.
PMID- 28494399
TI - Comparative toxic responses of male and female lizards (Eremias argus) exposed to
(S)-metolachlor-contaminated soil.
AB - Soil contamination caused by the widespread use of pesticides is one of the main
environmental problems facing conservation organizations. (S)-metolachlor (SM) is
a selective pre-emergent herbicide that poses potential risks to soil-related
organisms such as reptiles. The present study elucidated the toxic effects of SM
(3 and 30 mg/kg soil weight) in Eremias argus. The results showed that growth
pattern was similar between the sexes in breeding season. For males, both kidney
coefficient (KC) and testis coefficient in the exposure group were significantly
different from those in the control group, while only KC in the high-dose group
was significantly higher for females. Based on histopathological analysis, the
livers of female lizards were more vulnerable than those of males in the exposure
group. A reduction in total egg output was observed in SM exposed lizards.
Accumulation studies indicated that skin exposure may be an important route for
SM uptake in E. argus, and that the liver and lung have strong detoxification
abilities. In addition, the body burdens of the lizards increased with increasing
SM concentration in the soil.
PMID- 28494400
TI - Maternal serum lead level during pregnancy is positively correlated with risk of
preterm birth in a Chinese population.
AB - Lead (Pb) is a well-known developmental toxicant. The aim of the present study
was to analyze the association between maternal serum Pb level and risk of
preterm birth in a population-based birth cohort study. The present study
analyzed a sub-study of the China-Anhui Birth Cohort that recruited 3125 eligible
mother-and-singleton-offspring pairs. Maternal serum Pb level was measured by
graphite furnace atomic absorption spectrometry. All subjects were classified
into three groups by tertile division according to serum Pb level: Low-Pb (L-Pb,
<1.18 MUg/dl), Medium-Pb (M-Pb, 1.18-1.70 MUg/dl), and High-Pb (H-Pb, >=1.71
MUg/dl). The rate of preterm birth was 2.8% among subjects with L-Pb, 6.1% among
subjects with M-Pb, and 8.1% among subjects with H-Pb, respectively. After
controlling confounding factors, the adjusted OR for preterm birth was 2.33
(95%CI: 1.49, 3.65) among subjects with M-Pb and 3.09 (95%CI: 2.01, 4.76) among
subjects with H-Pb. Of interest, maternal Pb exposure in early gestational stage
than in middle gestational stage was more susceptible to preterm birth. Moreover,
maternal serum Pb level was only associated with increased risk of late preterm
birth. The present study provides evidence that maternal serum Pb level during
pregnancy is positively associated with risk of preterm birth in a Chinese
population.
PMID- 28494401
TI - Using two-dimensional correlation size exclusion chromatography (2D-CoSEC) to
explore the size-dependent heterogeneity of humic substances for copper binding.
AB - Knowledge of the heterogeneous distribution of humic substances (HS) reactivities
along a continuum of molecular weight (MW) is crucial for the systems where the
HS MW is subject to change. In this study, two dimensional correlation
spectroscopy combined with size exclusion chromatography (2D-CoSEC) was first
utilized to obtain a continuous and heterogeneous presence of copper binding
characteristics within bulk HS with respect to MW. HS solutions with varying
copper concentrations were directly injected into a size exclusion chromatography
(SEC) system with Tris-HCl buffer as a mobile phase. Several validation tests
confirmed neither structural disruption of HS nor competition effect of the
mobile phase used. Similar to batch systems, fluorescence quenching was observed
in the chromatograms over a wide range of HS MW. 2D-CoSEC maps of a soil-derived
HS (Elliot soil humic acid) showed the greater fluorescence quenching degrees
with respect to the apparent MW on the order of 12500 Da > 10600 Da > 7000 Da >
15800 Da. The binding constants calculated based on modified Stern-Volmer
equation were consistent with the 2D-CoSEC results. More heterogeneity of copper
binding affinities within bulk HS was found for the soil-derived HS versus an
aquatic HS. The traditional fluorescence quenching titration method using
ultrafiltered HS size fractions failed to delineate detailed distribution of the
copper binding characteristics, exhibiting a much shorter range of the binding
constants than those obtained from the 2D-CoSEC. Our proposed technique
demonstrated a great potential to describe metal binding characteristics of HS at
high MW resolution, providing a clear picture of the size-dependent metal-HS
interactions.
PMID- 28494402
TI - Polycyclic aromatic hydrocarbons in ocean sediments from the North Pacific to the
Arctic Ocean.
AB - Eighteen polycyclic aromatic hydrocarbons (PAHs) were measured in surficial
sediments along a marine transect from the North Pacific into the Arctic Ocean.
The highest average Sigma18PAHs concentrations were observed along the
continental slope of the Canada Basin in the Arctic (68.3 +/- 8.5 ng g-1 dw),
followed by sediments in the Chukchi Sea shelf (49.7 +/- 21.2 ng g-1 dw) and
Bering Sea (39.5 +/- 11.3 ng g-1 dw), while the Bering Strait (16.8 +/- 7.1 ng g
1 dw) and Central Arctic Ocean sediments (13.1 +/- 9.6 ng g-1 dw) had relatively
lower average concentrations. The use of principal components analysis with
multiple linear regression (PCA/MLR) indicated that on average oil related or
petrogenic sources contributed ~42% of the measured PAHs in the sediments and
marked by higher concentrations of two methylnaphthalenes over the non-alkylated
parent PAH, naphthalene. Wood and coal combustion contributed ~32%, and high
temperature pyrogenic sources contributing ~26%. Petrogenic sources, such as oil
seeps, allochthonous coal and coastally eroded material such as terrigenous
sediments particularly affected the Chukchi Sea shelf and slope of the Canada
Basin, while biomass and coal combustion sources appeared to have greater
influence in the central Arctic Ocean, possibly due to the effects of episodic
summertime forest fires.
PMID- 28494403
TI - HER2 status predicts for upfront AI benefit: A TRANS-AIOG meta-analysis of 12,129
patients from ATAC, BIG 1-98 and TEAM with centrally determined HER2.
AB - BACKGROUND: A meta-analysis of the effects of HER2 status, specifically within
the first 2-3 years of adjuvant endocrine therapy, has the potential to inform
patient selection for upfront aromatase inhibitor (AI) therapy or switching
strategy tamoxifen followed by AI. The pre-existing standardisation of
methodology for HER2 (immunohistochemistry/fluorescence in situ hybridization)
facilitates analysis of existing data for this key marker. METHODS: Following a
prospectively designed statistical analysis plan, patient data from 3 phase III
trials Arimidex, Tamoxifen, Alone or in Combination Trial (ATAC), Breast
International Group (BIG) 1-98 and Tamoxifen Exemestane Adjuvant Multicentre
Trial (TEAM)] comparing an AI to tamoxifen during the first 2-3 years of adjuvant
endocrine treatment were collected and a treatment-by-marker analysis of distant
recurrence-free interval-censored at 2-3 years treatment - for HER2 status * AI
versus tamoxifen treatment was performed to address the clinical question
relating to efficacy of 'upfront' versus 'switch' strategies for AIs. RESULTS: A
prospectively planned, patient-level data meta-analysis across 3 trials
demonstrated a significant treatment (AI versus tamoxifen) by marker (HER2)
interaction in a multivariate analysis; (interaction hazard ratio [HR] = 1.61,
95% CI 1.01-2.57; p < 0.05). Heterogeneity between trials did not reach
statistical significance. The HER2 negative (HER2-ve) group gained greater
benefit from AI versus tamoxifen (HR = 0.70, 95% CI 0.56-0.87) than the HER2
positive (HER2+ve) group (HR = 1.13, 95% CI 0.75-1.71). However, the small number
of HER2+ve cases (n = 1092 across the 3 trials) and distant recurrences (n = 111)
may explain heterogeneity between trials. CONCLUSIONS: A patient-level data meta
analysis demonstrated a significant interaction between HER2 status and treatment
with AI versus tamoxifen in the first 2-3 years of adjuvant endocrine therapy.
Patients with HER2-ve cancers experienced improved outcomes (distant relapse)
when treated with upfront AI rather than tamoxifen, whilst patients with HER2+ve
cancers fared no better or slightly worse in the first 2-3 years. However, the
small number of HER2+ve cancers/events may explain a large degree of
heterogeneity in the HER2+ve groups across all 3 trials. Other causes, perhaps
related to subtle differences between AIs, cannot be excluded and warrant further
exploration.
PMID- 28494404
TI - Treatment and pattern of bone metastases in 1094 patients with advanced breast
cancer - Results from the prospective German Tumour Registry Breast Cancer cohort
study.
AB - A high proportion of patients with breast cancer develop bone metastases, yet
data on routine treatment with bone-targeted agents (BTA) are rare. We report
real-life outcome data of patients with breast cancer metastasised to the bone
treated by office-based oncologists in Germany. The ongoing, prospective,
multicentre, population-based cohort study Tumour Registry Breast Cancer (TMK)
was started in 2007 in 140 centres across Germany. This interim analysis of 1094
patients with bone metastases revealed differences among the tumour subtypes: at
start of first-line therapy, 36% of the patients with hormone receptor (HR)
positive and only 20% of the patients with HR-negative tumours presented with
bone-only metastasis. The majority of patients with bone metastases (89%, n =
976) received BTA therapy. In 2014-2015, 37% of the patients received the
bisphosphonate zoledronic acid and 36% the antibody denosumab. Median duration of
BTA therapy was 20 months (interquartile range 31.5 months), starting a median of
3 weeks after diagnosis of bone metastases, and ending a median of 7 weeks before
death. The median overall survival (OS) also varied among the types of metastasis
at start of first-line therapy ranging from 54 months (95% confidence interval
[CI] 37.6-70.8), 38 months (95% CI 29.4-44.2) to 28 months (95% CI 24.2-31.0) for
patients with bone-only metastases, non-visceral with or without bone metastases
and visceral with or without bone metastases respectively. We show that choice
and duration of BTA therapies are in conformity with guidelines applicable in
Germany. To our knowledge, this is the first presentation of data on incidence,
metastatic pattern, treatment and survival of patients with bone metastases in
routine practice.
PMID- 28494405
TI - Radical treatment of oligometastatic non-small cell lung cancer: Ready for prime
time?
AB - Oligometastatic non-small cell lung cancer (NSCLC), defined as a disease with low
metastatic burden and limited organ involvement, is conceived as an intermediate
condition between a truly localised disease and a widely metastatic tumour.
Traditionally, local ablative therapies (LATs), such as surgery and radiotherapy,
have been limited to symptoms' palliation in advanced NSCLC. Several
retrospective studies suggest that using local ablative therapy for
oligometastatic disease could offer good local control of the disease and
improvement in terms of progression-free survival. The first randomised study of
local consolidative therapy versus maintenance therapy or observation in
oligometastatic NSCLC has been recently published. The results of this phase II
trial showed an impressive improvement in median progression-free survival with
local therapy and a delay in the appearance of new lesions, suggesting a
systemically extended benefit of consolidation therapies. Nevertheless, further
confirmation of this evidence with additional future trials is needed to
definitively consider the combination of local treatment techniques with novel
systemic agents recently approved for NSCLC therapy, such as immune checkpoint
inhibitors.
PMID- 28494406
TI - Relative dose intensity as a proxy measure of quality and prognosis in adjuvant
chemotherapy for breast cancer in daily clinical practice.
AB - AIM: Adjuvant chemotherapy treatment of women with breast cancer is frequently
complicated by toxic side-effects, resulting in dose reduction and delay. In
Dutch guidelines, a relative dose intensity (RDI) of at least 85% is recommended
for optimal treatment. The aim was to investigate predictors of low RDI and its
effect on prognosis. METHODS: All patients treated in the St. Antonius Hospital
with adjuvant chemotherapy for breast cancer between 2008 and 2013 were included
(N = 605). RDI was calculated for each single chemotherapeutic agent and for
chemotherapy regimens in total. Incidence and causes of RDI <85% were studied, as
well as the effect of RDI on prognosis. RESULTS: About 10% of 605 patients had
RDIs <85%. Predictive factors included age, episodes of febrile neutropenia and
grade III or IV hypersensitivity reaction to taxanes. Other adverse events, such
as peripheral neuropathy, did not affect RDI. The incidence of febrile
neutropenia in the 5-fluorouracil, epirubicin, cyclofosfamide, docetaxel (FEC-D)
protocol was 24% and therefore was above the threshold set by the European
Organisation for Research and Treatment of Cancer for primary granulocyte colony
stimulating factor (G-CSF) prophylaxis. No relationship between RDI and (disease
free) survival was found with a median follow-up of 38 months. Apart from the
stage of disease, obesity is a predictor of poor outcome. CONCLUSIONS: RDI <85%
is predicted by patients' age, febrile neutropenia and hypersensitivity reactions
to taxanes. The incidence of febrile neutropenia in FEC-D treatment indicates
primary prophylaxis with G-CSF following docetaxel treatment. No relationship was
found between RDI and (disease-free) survival, but longer follow-up is needed.
PMID- 28494407
TI - Streptococcus mutans membrane lipid composition: Virulence factors and structural
parameters.
AB - OBJECTIVE: The aim of the present work was to analyze whether the location of the
dental biofilm was associated with shifts in the membrane fatty acid profile, and
whether such shifts could affect certain virulence factors of strains of
Streptococcus mutans. DESIGN: An experimental study was conducted to assess the
behavior of S. mutans strains isolated from dental biofilm collected from sound
and carious smooth and occlusal surfaces of the oral cavity of children. The
lipid composition of the bacterial membrane, structural membrane parameters, acid
survival, and ATPase activity were tested at pH 7 and 5. RESULTS: At pH 5, an
increase in both the unsaturated and the long chain fatty acids as well as in
proton ATPase hydrolytic activity was observed in strains isolated from carious
smooth surface biofilm but not in carious occlusal surface strains. The observed
changes correlated with the studied structural parameters, and were found to be
associated with membrane organization. The changes correlated with a decreased in
DeltaC (sn-1 and sn-2 acyl chain inequivalence), indicative of increased acyl
chain interaction. CONCLUSIONS: The obtained results suggest that the acidic
environment (pH 5) of smooth surface caries affects membrane organization,
inducing a shift in membrane lipid profile, which would likely induce better
protein/lipid hydrophobic matching, resulting in increased ATPase activity and
higher acid survival.
PMID- 28494408
TI - Solubilisation of oils in aqueous solutions of a random cationic copolymer.
AB - HYPOTHESIS: Reports of random copolymers capable of solubilising hydrophobic oils
are rare. This is primarily because random copolymers are unlikely to self
assemble into suitable aggregates (or micelles) in water. A random copolymer with
a "blocky" (or lumpy) microstructure may have potential to solubilise hydrophobic
oils in water. This type of polymer would have advantages over block copolymers
which are more laborious and costly to synthesise. EXPERIMENTS: The solubilising
capacity of a blocky random copolymer, namely poly(methyl methacrylate-co-2
dimethylaminoethyl methacrylate) (PMMA-co-PDMAEMA) is assessed by UV-visible
spectroscopy and compared with common reference surfactants. The relative
solubilising performance of random copolymers (across a narrow range of DMAEMA
mol % fraction) for aromatic and aliphatic oils was also studied. The morphology
of the aggregates was monitored as a function of the solubilisation capacity by
small-angle neutron scattering (SANS) and dynamic-light scattering (DLS).
FINDINGS: Similarly to well-defined block copolymers, these random copolymers
have a specific preference for solubilising aromatic over aliphatic oils.
Increasing hydrophobicity of the copolymer enhances the solubilisation capacity.
SANS has highlighted that aggregates become swollen and more uniform/spherical
with increasing concentration of aromatic solubilisate, and that the aromatic
solubilisate partitions throughout the random copolymer aggregates.
PMID- 28494409
TI - Effect of alkaline pretreatment on mesophilic and thermophilic anaerobic
digestion of a submerged macrophyte: Inhibition and recovery against dissolved
lignin during semi-continuous operation.
AB - The long-term effect of alkaline pretreatment on semi-continuous anaerobic
digestion (AD) of the lignin-rich submerged macrophyte Potamogeton maackianus was
investigated using mesophilic and thermophilic conditions. In pretreated
reactors, dissolved lignin accumulated to high levels. CH4 production under the
pretreated condition was higher than that of the untreated condition, but
decreased from Days 22 (mesophilic) and 42 (thermophilic). However, CH4
production subsequently recovered, although dissolved lignin accumulated.
Further, the change in the microbial community was observed between conditions.
These results suggest that dissolved lignin temporarily inhibited AD, although
acclimatization to dissolved lignin occurred during long-term operation. During
the steady state period, mesophilic conditions achieved a 42% increase in the CH4
yield using pretreatment, while thermophilic conditions yielded an 8% increment.
Because volatile fatty acids accumulated even after acclimatization during the
thermophilic pretreated condition and was discharged with the effluent,
improvement of the methanogenic step would enable enhanced CH4 recovery.
PMID- 28494410
TI - Carboxylic acid functionalized sesame straw: A sustainable cost-effective
bioadsorbent with superior dye adsorption capacity.
AB - This study prepared a carboxylic functionalized bioadsorbent that met the "4-E"
criteria: Efficient, Economical, Environmentally friendly, and Easily-produced.
Sesame straw (Sesamum indicum L.) was functionalized through treatment with
citric acid (SSCA) and tartaric acid (SSTA). The products were examined for
adsorption capacity and mechanisms. Langmuir model gave the best fit for the
isotherm data, and the maximum monolayer adsorption capacity of SSCA was 650mgg-1
for methylene blue (MB). The excellent dye adsorption capacity of SSCA can be
attributed to the introduction of ester groups during citric-acid modification
and the tube-like structures (i.e., sesame straw cell wall remnants). At last,
the cost of carboxylic acid functionalized bioadsorbents was evaluated, which
showed that SSCA would be the most cost-effective bioadsorbent. Additionally,
this study presents a thermo-decomposition methodology for contaminant-loaded
bioadsorbent. Results showed that SSCA is probably one of the few bioadsorbents
that can be produced and applied in industrial scale.
PMID- 28494411
TI - Deep eutectic solvents' ability to solubilize lignin, cellulose, and
hemicellulose; thermal stability; and density.
AB - An environmentally-friendly method to separate cellulose and hemicelluloses from
lignin in recalcitrant biomass for subsequent conversion is desirable to reduce
greenhouse gas generation. Easily-prepared, deep eutectic solvents (DESs) have
low volatility, wide liquid range, non-flammability, nontoxicity,
biocompatibility, and biodegradability. This study shows the DESs (formic
acid:choline chloride, lactic acid:choline chloride, acetic acid:choline
chloride, lactic acid:betaine, and lactic acid:proline) to be capable of
preferentially dissolving lignin at 60 degrees C. Thermogravimetric analysis show
DES to be stable at typical biomass processing temperatures. Pretreating loblolly
pine in one DES increased glucose yield after enzymatic hydrolysis to more than
seven times that of raw or glycerol-pretreated pine. The density of DES
pretreated biomass was found to be 40% higher than the untreated pine's density.
PMID- 28494412
TI - Long-term reliability and stability of behavioral measures among adolescents: The
Delay Discounting and Stroop tasks.
AB - Delay Discounting (DD) and the Stroop test are two fundamental tasks for the
assessment of impulsivity and inhibitory control, core features of several
behavioral disorders. Although the study of reliability and temporal stability is
important, only studies with adults and small samples have been carried out. The
aim of this study is to assess the one-year reliability and temporal stability of
both tasks among adolescents. A total of 1375 adolescents (M = 13.08 years old,
SD = 0.51) made up the final sample (53.5% males). The results showed moderate
stability and good reliability for both DD (alpha = 0.90) and Stroop (alpha =
0.85). Indices based on the reaction times and not the number of errors are
recommended when using the Stroop test. These results support the use of both
behavioral tasks in longitudinal research among adolescents.
PMID- 28494414
TI - Relationship violence victimization and binge drinking trajectories among a
nationally representative sample of adolescents.
AB - The present study evaluated the impact of relationship violence (RV)
victimization on the longitudinal trajectory of binge drinking (BD) among 3614 US
adolescents (51.2% male) who participated in an initial telephone interview
regarding physical and sexual RV victimization and binge drinking. Two follow-up
phone interviews were completed over approximately three years. Multilevel
modeling revealed small, but significant, increases in BD over time; older
adolescents and those who had ever experienced RV victimization were more likely
to report BD at Wave 1 compared to younger adolescents and non-victims. Although
new RV victimization reported during the study predicted an increase in the
likelihood of BD at that occasion, those who had ever experienced RV
victimization were less likely to report BD over time compared to non-victims.
Contrary to expectations, no sex differences emerged. Findings indicate that BD
may precede RV. Interventions to reduce alcohol-related RV may be especially
useful in this population.
PMID- 28494413
TI - Household chaos as a context for intergenerational transmission of executive
functioning.
AB - Executive functioning (EF) may be transmitted across generations such that
strengths or deficiencies in parent EF are similarly manifested in the child. The
present study examined the contributions of parent EF and impulsivity on
adolescent EF, and investigated whether household chaos is an environmental
moderator that alters these transmission processes. American adolescents (N =
167, 47% female, 13-14 years old at Time 1) completed behavioral measures of EF
and reported household chaos at Time 1 and one year later at Time 2. Parents
completed behavioral measures of EF and self-reported impulsivity at Time 1.
Results indicated that lower parent EF at Time 1 predicted lower adolescent EF at
Time 2 (controlling for adolescent EF and IQ at Time 1), but only in the context
of high household chaos. Findings suggest that household chaos may be a risk
factor that compounds influences of poor parent EF and compromises adolescent EF
development.
PMID- 28494415
TI - Studies on curative efficacy of monoterpene eugenol on anti- leukemic drug
arsenic trioxide induced cardiotoxicity.
AB - BACKGROUND: Arsenic trioxide (As2O3) is emerging as a frontline agent for the
treatment of acute promyelocytic leukemia (APL) but the therapeutic application
is limited by its toxicity. QT prolongation, torsades de pointes and sudden
cardiac death have been implicated in the As2O3 therapy. So eugenol is a
monoterpene compound is well known for its antioxidant properties and protective
effect on the cardiovascular system. OBJECTIVE: In this study, the
cardioprotective effect of eugenol on cardiac electrical conductivity, tissue
electrolytes, myocardial markers, antioxidant system, lipid peroxidation and
nitric oxide production was investigated in male Wistar rats treated with arsenic
trioxide. RESULTS: The Inductively coupled plasma emission spectroscopic (ICP
OES) analysis pointed out the accumulation of arsenic in heart tissue. The rats
administered with arsenic trioxide (4mg/kg body wt) exhibited myocardial damage
that was manifested by the elevation of cardiac markers (LDH, CK-MB) enzymes and
deterioration in the antioxidant enzymes (GSH, GST, GPx). Combination treatment
with eugenol (5mg/kg of body wt) upholds the tissue antioxidant level, Na+/K+ -
ATPase and Ca2+- ATPase activity and brings the cytosolic Ca2+, K+ and Na +
levels near to normal value. Conjoined therapy with eugenol ameliorated the
membrane peroxidation, restored the normal heart rate and rectified the
prolongation of QT interval in the electrocardiogram. Histological examination of
cardiac segments also supported the beneficial role of eugenol against arsenic
induced oxidative damages. CONCLUSION: Our in vivo experimental findings suggest
that monoterpenoid eugenol could be a potent and novel cytoprotective agent of
clinical application against As2O3 induced cardiotoxicity.
PMID- 28494416
TI - Ameliorative effect of vitamin E and selenium against oxidative stress induced by
sodium azide in liver, kidney, testis and heart of male mice.
AB - The study purported to define the effects of daily administration of vitamin E
(Vit E) and selenium (Se) on antioxidant enzyme activity in mice treated with
high doses of sodium azide (SA). Male mice were randomly split into nine groups.
Groups 1, 2 and 3 were injected daily with saline, Vit E, and Se, respectively,
while groups 4, 5 and 6 administrated with different doses of SA (low, medium and
high, respectively). The mice in groups 7, 8 and 9 received 100mg/kg Vit E,
17.5mg/kg Se, and a combination of Vit E and Se, respectively before the SA
treatment. Hepatic, renal, testis and heart, antioxidant enzymes as well as
levels of lipid peroxidation and total antioxidant capacity levels were
determined. Vit E alone affected on the antioxidant parameters of the examined
tissues. Se had a preventive effect on the decrease of antioxidant parameters
caused by SA and improved the diminished activities of all of them. The study
demonstrates that a high dose of SA may alter the effects of normal level
antioxidant/oxidative status of male mice and that Se is effective in reducing
the SA-damage. Se acts as a synergistic agent with the effect of Vit E in various
damaged caused by SA.
PMID- 28494417
TI - The role of free kappa and lambda light chains in the pathogenesis and treatment
of inflammatory diseases.
AB - Kappa (kappa) or lambda (lambda) free light chains (FLCs) are produced from B
cells during immunoglobulin synthesis. FLCs have been shown to participate in
several key processes of immune responses. They are necessary to adjust PMN
functions and assist PMN pre-stimulation. Moreover, they cause mast cell
degranulation which releases pro-inflammatory mediators and stimulates local
inflammatory responses in some conditions such as inflammatory bowel disease
(IBD). Having low molecular weights which may straightly be toxic to proximal
tubule cells (PTCs), FLCs can also have an important role in renal diseases. In
this review we have highlighted the involvement of light chains in the
pathogenesis of some inflammatory diseases and discussed their potential to be
the targets of therapeutic purposes.
PMID- 28494418
TI - Zingiber officinale and 6-gingerol alleviate liver and kidney dysfunctions and
oxidative stress induced by mercuric chloride in male rats: A protective
approach.
AB - Mercury toxicity is an emerging problem in the world as its concentration is
rising continuously due to increased industrial, medicinal and domestic uses.
Exposure to mercury represents a serious challenge to humans and other living
biomes. The aim of the present study was to assess the protective effect of
natural products as Zingiber officinale extract and its active compound (6
gingerol) against mercuric chloride-induced hepatorenal toxicity and oxidative
stress in male rats. Male Sprague-Dawley rats (150+/-10g, n=6 per group) were
administered HgCl2 (12MUmol/kg, ip; once only) the treatment of Zingiber
officinale Rosc. extract (ZO: 125mg/kg, po) and 6-gingerol (GG: 50mg/kg, po) for
three days after 24h of HgCl2 administration. Acute HgCl2 administration altered
various biochemical parameters, including transaminases, alkaline phosphatase,
lactate dehydrogenase, bilirubin, gamma-glutamyl transferase, triglycerides and
cholesterol, urea, creatinine, uric acid and blood urea nitrogen contents with a
concomitant decline in protein and albumin concentration in serum. In addition, a
significant rise in lipid peroxidation level with concomitant decrease in reduced
glutathione content and the antioxidant enzymes activities of superoxide
dismutase, catalase, glutathione reductase, glutathione peroxidase and
glutathione-S-transferase after acute HgCl2 exposure. Results of the present
investigation clearly showed that both treatments as Zingiber officinale extract
and 6-gingerol provide protection against acute mercuric chloride-intoxication by
preventing oxidative degradation of a biological membrane from metal mediated
free radical attacks. Biochemical data were well supported by histopathological
findings. In conclusion, natural products may be an ideal choice against
oxidative damage induced by mercury poisoning.
PMID- 28494419
TI - Neuroprotective effects of total flavonoid fraction of the Epimedium koreanum
Nakai extract on dopaminergic neurons: In vivo and in vitro.
AB - Flavonoids, the active components of Epimedii Genus, have been demonstrated to
protect against osteoporosis, cardiovascular diseases and rheumatoid arthritis.
The present study aimed to investigate the neuroprotective effects of total
flavonoid (TF) fraction of Epimedium koreanum Nakai on dopaminergic neurons in
the cellular and mice models of Parkinson's disease (PD). TF pretreatment could
ameliorate the decrease of striatal dopamine (DA) content and the loss of
tyrosine hydroxylase (TH)-immunoreactive neurons in the substantia nigra pars
compacta (SNpc) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
TF treatment could reverse the changes of Bcl-2 and Bax protein expressions in
the striatum of PD mice. 1-Methyl-4-phenylpyridinium ion (MPP+) significantly
decreased the cell viability and mitochondrial membrane potential in MES23.5
cells. These effects could be reversed by TF treatment. In addition, MPP+-induced
changes of Bcl-2 and Bax mRNA and protein expressions were also reversed by TF
pretreatment. These data demonstrated that TF of E. koreanum Nakai could protect
against MPTP-induced dopaminergic neuronal death in mice and MPP+-induced
neurotoxicity in dopaminergic MES23.5 cells. Anti-apoptosis might be involved in
this process.
PMID- 28494420
TI - Egg shell waste as heterogeneous nanocatalyst for biodiesel production: Optimized
by response surface methodology.
AB - Worldwide consumption of hen eggs results in availability of large amount of
discarded egg waste particularly egg shells. In the present study, the waste
shells were utilized for the synthesis of highly active heterogeneous calcium
oxide (CaO) nanocatalyst to transesterify dry biomass into methyl esters
(biodiesel). The CaO nanocatalyst was synthesied by calcination-hydration
dehydration technique and fully characterized by infrared spectroscopy, X-ray
powder diffraction (XRD), scanning electron microscope (SEM), transmission
electron microscope (TEM), brunauer-emmett-teller (BET) elemental and
thermogravimetric analysis. TEM image showed that the nano catalyst had spherical
shape with average particle size of 75 nm. BET analysis indicated that the
catalyst specific surface area was 16.4 m2 g-1 with average pore diameter of 5.07
nm. The effect of nano CaO catalyst was investigated by direct
transesterification of dry biomass into biodiesel along with other reaction
parameters such as catalyst ratio, reaction time and stirring rate. The impact of
the transesterification reaction parameters and microalgal biodiesel yield were
analyzed by response surface methodology based on a full factorial, central
composite design. The significance of the predicted mode was verified and 86.41%
microalgal biodiesel yield was reported at optimal parameter conditions 1.7%
(w/w), catalyst ratio, 3.6 h reaction time and stirring rate of 140.6 rpm. The
biodiesel conversion was determined by 1H nuclear magnetic resonance spectroscopy
(NMR). The fuel properties of prepared biodiesel were found to be highly comply
with the biodiesel standard ASTMD6751 and EN14214.
PMID- 28494421
TI - Forest protected areas governance in Zimbabwe: Shift needed away from a long
history of local community exclusion.
AB - In this literature review based paper we explored the concept of exclusion of
local communities from accessing resources in forest protected areas (FPAs) in
Zimbabwe. We discussed the colonial and post-colonial forms, causes and
mechanisms of exclusion and their social, economic and ecological outcomes. We
examined the range of powers embodied in and exercised through various
mechanisms, processes and social relations and their impact on local communities'
access to FPA resources and associated benefits along the historical trajectory
of forest governance in Zimbabwe. Results showed that the forms and extent of
exclusion changed over time in tandem with the shifting political and economic
landscape. During the colonial period, it was total exclusion whereby people were
evicted from forest land as well as being denied access to basic resources for
their livelihoods. Local communities' access to low value FPA resources improved
during the post-colonial period but access to high value resources like
commercial timber as well as sharing income benefits derived from FPA commercial
activities remained a pipe dream. Regulation, legitimation, force and markets
constituted the mixture of the power elements that FPA governing authorities used
to exclude local communities. These powers remained intact despite attempts at
collaborative governance in the 1990s. However, from the year 2000, local
communities expressed their dissatisfaction with the centralised exclusionary
governance system by invading the FPAs rendering them ungovernable. There is
therefore a need for policy reform within the FPA sector to improve the current
dire situation.
PMID- 28494422
TI - Cyanobacteria blooms before and during the restoration process of a shallow urban
lake.
AB - Swarzedzkie Lake (near Poznan) has been heavily polluted. To improve the water
quality, the restoration of lake by three methods: aeration, phosphorus
inactivation using small doses of iron sulphate and magnesium chloride (FeSO4 and
MgCl2) and biomanipulation was initiated at the end of 2011. The aim of the
present study was to determine whether sustainable restoration has a significant
impact on phytoplankton, especially cyanobacterial blooms in a shallow, urban,
degraded lake. Therefore, phytoplankton and the physico-chemical parameters of
water at the summer thermal stratification and autumn water mixing before (2011)
and during restoration (2012-2014) was studied. Samples were collected at the
deepest place of the lake in depth profile, every 1 m. Phytoplankton samples were
preserved with Lugol's solution. The phytoplankton was counted using a Sedgewick
Rafter chamber with a volume of 0.46 ml. Measurements of water temperature were
made in the field with a YSI multiparameter meter, transparency - using a Secchi
disk. Concentrations of nitrogen, phosphorus and chlorophyll a were analysed in
the laboratory according to Polish standards. As a result of restoration the
water quality of the lake has improved. Cyanobacteria had almost disappeared
during the first year of restoration, however, a short bloom was observed
(dominated by Pseudanabeana limnetica) in the second year. The main reason for
this reappearance was a higher water temperature stimulating cyanobacteria
growth, but an increased supply of phosphorus from the bottom sediments also
contributed. A decrease in the temperature in the third year of restoration
limited the growth of cyanobacteria again. Although the decrease in the
phosphorus concentration as a result of restoration proved to be sufficient for
average climatic conditions, it is highly likely to be more intense in the case
of increased water temperature caused by global warming.
PMID- 28494423
TI - Investigating sources of pharmaceutical pollution: Survey of over-the-counter and
prescription medication purchasing, use, and disposal practices among university
students.
AB - Pharmaceutical pollution in surface waters poses a range of risks to public
health and aquatic ecosystems. Consumers contribute to pharmaceutical pollution
via use and disposal of medications, though data on such behaviors is limited.
This paper investigates the purchasing, use, and disposal practices among a
population that has been researched only minimally to date, yet will determine
pharmaceutical pollution for decades to come: young adults represented by a
university student population. We employed an online, 21-question survey to
examine behaviors related to pharmaceuticals among students at the University of
Vermont (n = 358). Results indicate that the majority of respondents had
purchased medications in the previous 12 months (94%), and had leftover drugs
(61%). Contrary to previous studies of older populations, only a small proportion
of students had disposed of drugs (18%); municipal trash was the primary route of
drug disposal (25%), and very few students disposed drugs via flushing (1%). Less
than a quarter of students were aware of drug take-back programs (24%), and only
4% had ever used take-back services. These findings indicate that the university
student population may be storing a large volume of unused drugs that will
require future disposal. Increasing awareness of, access to, and participation in
pro-environment pharmaceutical behaviors, such as purchasing over-the-counter
medication in smaller quantities and utilizing drug take-back programs, could
minimize future pharmaceutical pollution from this population.
PMID- 28494424
TI - Is environmental sustainability a strategic priority for logistics service
providers?
AB - Despite an increasing number of third-party logistics service providers (3PLs)
regard environmental sustainability as a key area of management, there is still
great uncertainty on how 3PLs implement environmental strategies and on how they
translate green efforts into practice. Through a multiple case study analysis,
this paper explores the environmental strategies of a sample of medium-sized 3PLs
operating in Italy and the UK, in terms of environmental organizational culture,
initiatives, and influencing factors. Our analysis shows that, notwithstanding
environmental sustainability is generally recognised as a strategic priority, a
certain degree of diversity in the deployment of environmental strategies still
exists. This paper is original since the extant literature on green strategies of
3PLs provides findings predominantly from a single country perspective and mainly
investigates large/multinational organizations. It also provides indications to
help managers of medium-sized 3PLs in positioning their business. This is
particularly meaningful in the 3PL industry, where medium-sized organizations
significantly contribute to the generated turnover and market value.
PMID- 28494425
TI - Application of the WEAP model in strategic environmental assessment: Experiences
from a case study in an arid/semi-arid area in China.
AB - This article investigated how the use of a water resources assessment model
contributed to one of the first strategic environmental assessments (SEA)
conducted for arid/semi-arid regions in China. The study was based on the SEA of
a coal industry development plan in Ordos, an arid/semi-arid region of northwest
China, where a temporally and spatially simplified version of the WEAP (Water
Evaluation And Planning System) model was applied for assessing the impact of the
planned activities on local water resource system. Four scenarios were developed
to simulate various alternatives using a diverse range of water utilisation
measures such as irrigation efficiency, treatment and the reuse of water. The
WEAP model itself was found to be a useful tool for efficient water resources
assessment in SEA: 1) WEAP provides built-in simulation modules for water
assessment, which improve the SEA's efficiency significantly; 2) WEAP temporally
has the flexibility in both delivering information on a reasonably aggregated
level by evaluating water resource on an annual time step, which fits most SEA
cases, and being possible to take a finer time step analysis monthly, weekly even
daily; 3) Spatially, WEAP has advantage in dealing with distributed demand sites
in large spatial scale. However, although WEAP appears as a useful tool in
providing support for decision-making, in this SEA case we experienced difficulty
in building a feasible scenario to mitigate the impact of the proposed activities
on the local water system, so that solution had to be found outside of the
assessed scenarios - which led to the discussion on the fact that the proposed
activities in SEA cases are rarely regarded as an uncertainty. Therefore future
research on the scope of SEA scenarios could be valuable.
PMID- 28494426
TI - The performance of the intensified constructed wetlands for organic matter and
nitrogen removal: A review.
AB - The effects of different aeration strategies including tidal flow (TF), effluent
recirculation (ER) and artificial aeration (AA) on performance of vertical flow
constructed wetland (VFCW), horizontal flow constructed wetland (HFCW) and hybrid
constructed wetland (HCW) are comprehensively and critically reviewed in this
paper. The removal efficiencies of nine types of intensified constructed wetlands
(CWs) were examined in detail and their mean and standard deviation were
estimated at 89 +/- 11%, 84 +/- 12%, 81 +/- 17% and 63 +/- 20% for total
suspended solids (TSS), chemical oxygen demand (COD), ammonium-nitrogen (NH4+N)
and total nitrogen (TN), respectively. From the studied CWs, ER-HCW, TF-HCW, AA
VFCW and ER-VFCW emerged as the four best performing systems. The overall removal
efficiency of TSS, COD, NH4+N and TN by ER-HCW was 98 +/- 2%, 85 +/- 11%, 83 +/-
15% and 73 +/- 11%, respectively. Specifically, the ER enhances the interactions
between pollutants and micro-organisms, consequently, the efficient removal of
NH4+N and TN has been achieved in ER-HCW. The TF has a positive effect in
refreshing the wetland with fresh air to enhance the dissolved oxygen (DO) in the
system. In case of AA, intermittent aeration is more effective than continuous
aeration, as it facilitates the establishment of aerobic and anaerobic conditions
suitable for nitrification and denitrification. Statistical analysis shows that
DO, organic loading rate and specific surface area requirement are the most
significant factors that influence the performance of intensified CWs.
PMID- 28494427
TI - On-line detection of Escherichia coli intrusion in a pilot-scale drinking water
distribution system.
AB - Improvements in microbial drinking water quality monitoring are needed for the
better control of drinking water distribution systems and for public health
protection. Conventional water quality monitoring programmes are not always able
to detect a microbial contamination of drinking water. In the drinking water
production chain, in addition to the vulnerability of source waters, the
distribution networks are prone to contamination. In this study, a pilot-scale
drinking-water distribution network with an on-line monitoring system was
utilized for detecting bacterial intrusion. During the experimental Escherichia
coli intrusions, the contaminant was measured by applying a set of on-line
sensors for electric conductivity (EC), pH, temperature (T), turbidity, UV
absorbance at 254 nm (UVAS SC) and with a device for particle counting. Monitored
parameters were compared with the measured E. coli counts using the integral
calculations of the detected peaks. EC measurement gave the strongest signal
compared with the measured baseline during the E. coli intrusion. Integral
calculations showed that the peaks in the EC, pH, T, turbidity and UVAS SC data
were detected corresponding to the time predicted. However, the pH and
temperature peaks detected were barely above the measured baseline and could
easily be mixed with the background noise. The results indicate that on-line
monitoring can be utilized for the rapid detection of microbial contaminants in
the drinking water distribution system although the peak interpretation has to be
performed carefully to avoid being mixed up with normal variations in the
measurement data.
PMID- 28494429
TI - Decompose the association between heatwave and mortality: Which type of heatwave
is more detrimental?
AB - BACKGROUND: Heatwaves is the most hazardous natural disaster in Australia and its
health impacts need to be well unveiled, but how to properly define a heatwave is
still debatable. This study aimed to identify which type of heatwave is more
detrimental to health and to elucidate which temperature indicator is more
suitable for heatwave definition and early warning. METHODS: We categorized
temperature into extremely-hot and not-extremely-hot, and extremely-hot
temperature refers to temperature at least >=96th percentile of the monthly
temperature distribution, and accordingly, heatwaves were categorized into four
types: 1) Type I: extremely-hot days followed by extremely-hot nights (HWboth);
2) Type II: extremely-hot days followed by not-extremely-hot nights (HWday); 3)
Type III: not-extremely-hot days followed by extremely-hot nights (HWnight); and
4) Type IV: not-extremely-hot days followed by not-extremely-hot nights (HWwarm).
A Poisson regression allowing for over-dispersion was used to examine the
relationship between different types of heatwaves and mortality in Sydney,
Melbourne and Brisbane using the data from 1988 to 2011. RESULTS: Mortality in
Brisbane increased significantly during HWboth and HWwarm, and mortality in
Melbourne increased significantly during HWboth and HWday. For Sydney, HWboth,
HWwarm, and HWday were all associated with mortality increase, although no
appreciable difference in the magnitudes of mortality increase among these three
heatwave types was observed. HWnight was not associated with any significant
mortality increase in these cities. Mean temperature is the best temperature
indicator for heatwaves in Brisbane and maximum temperature is the best
temperature indicator for heatwaves in Melbourne. CONCLUSIONS: Extremely-hot days
rather than extremely-hot nights played a critical role in heatwave-related
mortality. City-specific heatwave early warning may be optimal for Australia.
PMID- 28494428
TI - Shotgun lipidomics in substantiating lipid peroxidation in redox biology: Methods
and applications.
AB - Multi-dimensional mass spectrometry-based shotgun lipidomics (MDMS-SL) has made
profound advances for comprehensive analysis of cellular lipids. It represents
one of the most powerful tools in analyzing lipids directly from lipid extracts
of biological samples. It enables the analysis of nearly 50 lipid classes and
thousands of individual lipid species with high accuracy/precision. The redox
imbalance causes oxidative stress, resulting in lipid peroxidation, and
alterations in lipid metabolism and homeostasis. Some lipid classes such as
oxidized fatty acids, 4-hydroxyalkenal species, and plasmalogen are sensitive to
oxidative stress or generated corresponding to redox imbalance. Therefore,
accurate assessment of these lipid classes can provide not only the redox states,
but also molecular insights into the pathogenesis of diseases. This review
focuses on the advances of MDMS-SL in analysis of these lipid classes and
molecular species, and summarizes their recent representative applications in
biomedical/biological research. We believe that MDMS-SL can make great
contributions to redox biology through substantiating the aberrant lipid
metabolism, signaling, trafficking, and homeostasis under oxidative stress
related condition.
PMID- 28494430
TI - Novel cosmetic formulations containing a biosurfactant from Lactobacillus
paracasei.
AB - Cosmetic and personal care products including toothpaste, shampoo, creams,
makeup, among others, are usually formulated with petroleum-based surfactants,
although in the last years the consume trend for "green" products is inducing the
replacement of surface-active agents in these formulations by natural
surfactants, so-called biosurfactants. In addition to their surfactant capacity,
many biosurfactants can act as good emulsifiers, which is an extra advantage in
the preparation of green cosmetic products. In this work, a biosurfactant
obtained from Lactobacillus paracasei was used as a stabilizing agent in oil-in
water emulsions containing essential oils and natural antioxidant extract. In the
presence of biosurfactant, maximum percentages of emulsion volumes (EV=100%) were
observed, with droplets sizes about 199nm. These results were comparable with the
ones obtained using sodium dodecyl sulfate (SDS), a synthetic well known
surfactant with high emulsify capacity. Moreover, the biosurfactant and emulsions
cytotoxicity was evaluated using a mouse fibroblast cell line. Solutions
containing 5g/L of biosurfactant presented cell proliferation values of 97%,
whereas 0.5g/L of SDS showed a strong inhibitory effect. Overall, the results
herein gathered are very promising towards the development of new green cosmetic
formulations.
PMID- 28494431
TI - Silica nanoparticles as sources of silicic acid favoring wound healing in vitro.
AB - There is good evidence that certain silicon-containing materials promote would
healing and their common feature is the delivery of orthosilicic acid (Si(OH)4)
either directly or following metabolism. In this respect, amorphous silica
nanoparticles (NP), which dissolve in aqueous environments releasing up to 2mM
orthosilicic acid, may be appropriate 'slow release' vehicles for bioactive
silicon. Here we studied the impact of silica NP suspensions (primary
particles~10nm) in undersaturated conditions (below 2mM Si) with differing
degrees of surface charge and dissolution rate on human dermal fibroblasts (CCD
25SK cells) viability, proliferation and migration in a cellular wound model.
Silica was shown to be non-toxic for all forms and concentrations tested and
whilst the anticipated stimulatory effect of orthosilicic acid was observed, the
silica NPs also stimulated fibroblast proliferation and migration. In particular,
the amine-functionalized particles promoted wound closure more rapidly than
soluble orthosilicic acid alone. We suggest that this effect is related to easy
cellular internalization of these particles followed by their intracellular
dissolution releasing silicic acid at a faster rate than its direct uptake from
the medium. Our findings indicate that amorphous silica-based NPs may favour the
delivery and release of bioactive silicic acid to cells, promoting wound healing.
PMID- 28494432
TI - Synthesis and evaluation of mucoadhesive acryloyl-quaternized PDMAEMA nanogels
for ocular drug delivery.
AB - Poly((2-dimethylamino)ethyl methacrylate) (PDMAEMA) nanogels were synthesized via
surfactant-free free-radical polymerization technique in aqueous conditions
utilizing N,N'-methylene-bis-acrylamide (MBA) as a crosslinking agent. The
PDMAEMA nanogels were subsequently quaternized with acryloyl chloride in order to
yield mucoadhesive materials which incorporate two mucoadhesive concepts;
electrostatic interactions and covalent bond forming acrylate groups. The native
PDMAEMA nanogels were found to exhibit good mucoadhesive properties on ex vivo
bovine conjunctival tissues, which was found to increase proportionally with the
degree of quaternization. With a view to determine the ocular drug delivery
capabilities of the materials, both quaternized and native nanogels were loaded
with pilocarpine hydrochloride via an absorption method, and their in vitro
release profiles were analysed. The nanogels were found to exhibit a high loading
capacity (>20% of total weight) and a sustained release over 6h.
PMID- 28494433
TI - Electrospun ultrathin PBAT/nHAp fibers influenced the in vitro and in vivo
osteogenesis and improved the mechanical properties of neoformed bone.
AB - Combining polyester scaffolds with synthetic nanohydroxyapatite (nHAp), which is
bioactive and osteoconductive, is a plausible strategy to improve bone
regeneration. Here, we propose the combination of PBAT [poly(butylene-adipate-co
terephthalate)] and synthetic nHAp (at 3 and 5wt%). PBAT is a relatively a new
polymer with low crystallinity and attractive biodegradability and mechanical
properties for orthopedic applications, however, with a still underexplored
potential for in vivo applications. Then, we performed a careful biological in
vitro and in vivo set of experiments to evaluate the influence of PBAT containing
two different nHAp loads. For in vitro assays, osteoblast-like MG63 cells were
used and the bioactivity and gene expression related to osteogenesis were
evaluated by qRT-PCR. For in vivo experiments, twenty-four male rats were used
and a tibial defect model was applied to insert the scaffolds. Micro-computed
tomography (Micro-CT) and histological analysis were used to assess e bone
neoformation after 6 weeks of implantation. Three point flexural tests measured
the mechanical properties of the neoformed bone. All scaffolds showed promising
in vitro properties, since they were not cytotoxic against MG-63 cells and
promoted high cell proliferation and formation of mineralized nodules. From a
mechanistic point-of-view, nHAp loading increased hydrophilicity, which in turn
allowed for a better adsorption of proteins and consequent changes in the
phenotypic expression of osteoblasts. nHAp induced better cellular responses
on/in the scaffolds, which was mainly attributed to its osteoconductive and
osteoinductive properties. Micro-CT images showed that nHAp at 3% and 5wt% led to
more effective bone formation, presenting the highest bone volume after 6 weeks
of implantation. Considering the three point flexural tests, 5wt% of nHAp
positively influenced the flexural mode of the neoformed bone, but the stiffiness
was similar between the 3% and 5wt% groups. In summary, this investigation
demonstrated great potential for the application of these novel scaffolds towards
bone regeneration and, thus, should be further studied.
PMID- 28494434
TI - P-Cadherin is necessary for retinal stem cell behavior in vitro, but not in vivo.
AB - Adult retinal stem cells (RSCs) are rare quiescent cells within the ciliary
epithelium of the eye, which is made up of non-pigmented N-Cadherin+ve inner and
pigmented P-Cadherin+ve outer cell layers. Through FACs and single cell analyses,
we have shown that RSCs arise from single cells from within the pigmented CE and
express P-Cadherin. However, whether the expression of P-Cadherin is required for
maintenance of the stem cell in vivo or in the formation of the clonal stem cell
spheres in vitro is not known. Using cadherin functional blocking antibody
experiments and a P-Cadherin -/- mouse to test whether the RSC population is
affected by the loss of P-Cadherin expression, our experiments demonstrate that
the RSCs reside in the pigmented CE layer and express P-Cadherin, which is
important to the formation of adherent sphere colonies in vitro, however P
Cadherin is not required for maintenance of RSCs in vivo.
PMID- 28494435
TI - Impact of respiratory viruses in hospital-acquired pneumonia in the intensive
care unit: A single-center retrospective study.
AB - BACKGROUND: Data on the frequency and role of respiratory viruses (RVs) in
hospital-acquired pneumonia (HAP) are still scarce. OBJECTIVES: We assessed the
proportion of RVs and their impact on the outcome of hospital-acquired pneumonia
(HAP) in the intensive care unit (ICU). STUDY DESIGN: Cases of HAP were
retrospectively selected among patients who underwent screening for RVs by
multiplex PCR (mPCR) in the ICU of a French tertiary care hospital from May 2014
to April 2016. ICU length of stay and in-hospital mortality were compared between
four groups defined according to the identified pathogens: virus only (V),
virus/bacteria (V/B), bacteria only (B) and no pathogen (Neg). When available,
previous mPCR was retrieved in order to assess possible chronic viral carriage.
RESULTS: Overall, 95/999 (10%) ICU patients who underwent mPCR had HAP
(V(17,18%), V/B(13,14%), B(60,63%), Neg(5,5%)). Median age was 61 years and 45
(47%) were immunocompromised. Influenza (27%) and rhinovirus (27%) were the most
common RVs. V/B group had higher mortality rate than B and V groups (62% vs. 40%
and 35%, p=0.3) and a significantly longer length of stay (31days (18-48)) than V
group (5days (3-11), p=0.0002)) and B group (14.5days (5.5-25.5), p=0.007)).
Among the 15 patients with available mPCR tests before viral HAP, seven were
negative and eight were positive corresponding to long-term carriage of community
acquired viruses. DISCUSSION: RVs were detected in 32% of HAP patients who
underwent mPCR. Two situations were encountered: (i) acute acquired viral
infection; (ii) long-term viral carriage (mostly rhinovirus) especially in
immunocompromised patients complicated by a virus/bacteria coinfection. The
latter was associated with a longer length of stay and a trend toward a higher
mortality.
PMID- 28494436
TI - Neuronal tetraploidization in the cerebral cortex correlates with reduced
cognition in mice and precedes and recapitulates Alzheimer's-associated
neuropathology.
AB - A controversy exists as to whether de novo-generated neuronal tetraploidy (dnNT)
occurs in Alzheimer's disease. In addition, the presence of age-associated dnNT
in the normal brain remains unexplored. Here we show that age-associated dnNT
occurs in both superficial and deep layers of the cerebral cortex of adult mice,
a process that is blocked in the absence of E2F1, a known regulator of cell cycle
progression. This blockage correlates with improved cognition despite compromised
neurogenesis in the adult hippocampus was confirmed in mice lacking the E2f1
gene. We also show that the human cerebral cortex contains tetraploid neurons. In
normal humans, age-associated dnNT specifically occurs in the entorhinal cortex
whereas, in Alzheimer, dnNT also affects association cortices prior to
neurofibrillary tangle formation. Alzheimer-associated dnNT is likely potentiated
by altered amyloid precursor protein (APP) processing as it is enhanced in the
cerebral cortex of young APPswe/PS1deltaE9 mice, long before the first amyloid
plaques are visible in their brains. In contrast to age-associated dnNT, enhanced
dnNT in APPswe/PS1deltaE9 mice mostly affects the superficial cortical layers.
The correlation of dnNT with reduced cognition in mice and its spatiotemporal
course, preceding and recapitulating Alzheimer-associated neuropathology, makes
this process a potential target for intervention in Alzheimer's disease.
PMID- 28494437
TI - Nanosecond pulsed electric field induced changes in cell surface charge density.
AB - This study reports that the surface charge density changes in Jurkat cells with
the application of single 60 nanosecond pulse electric fields, using atomic force
microscopy. Using an atomic force microscope tip and Jurkat cells on silica in a
0.01M KCl ionic concentration, we were able to measure the interfacial forces,
while also predicting surface charge densities of both Jurkat cell and silica
surfaces. The most important finding is that the pulsing conditions varyingly
reduced the cells' surface charge density. This offers a novel way in which to
examine cellular effects of pulsed electric fields that may lead to the
identification of unique mechanical responses. Compared to a single low field
strength NsPEF (15kV/cm) application, exposure of Jurkat cells to a single high
field strength NsPEF (60kV/cm) resulted in a further reduction in charge density
and major morphological changes. The structural, physical, and chemical
properties of biological cells immensely influence their electrostatic force; we
were able to investigate this through the use of atomic force microscopy by
measuring the surface forces between the AFM's tip and the Jurkat cells under
different pulsing conditions as well as the interfacial forces in ionic
concentrations.
PMID- 28494438
TI - Assessment of Intra- and Inter-Rater Reliability of Three Methods for Measuring
Atopic Dermatitis Severity: EASI, Objective SCORAD, and IGA.
AB - BACKGROUND: Numerous different scoring systems have been proposed for assessing
the severity of atopic dermatitis (AD). Many of these methods did not undergo
proper validation and reliability testing. OBJECTIVE: The aim of our study was to
compare the reliability and reproducibility of the Eczema Area and Severity Index
(EASI), objective Scoring Atopic Dermatitis (oSCORAD), and Investigator Global
Assessment (IGA). METHODS: On the scoring day, 10 trained dermatologists
evaluated 10 adult patients with AD using the EASI, oSCORAD, and IGA. All
subjects were assessed twice by each physician. Correlations between measures
were analysed using the Pearson correlation coefficient. The intra-class
correlation coefficient (ICC) was calculated to assess intra-rater reliability;
the coefficient of variation (CV) was used to assess inter-rater variability.
RESULTS: Significant positive correlations were observed between each scale in
both assessments. The ICCs for the EASI and oSCORAD were 0.71 and 0.66,
respectively, indicating good reliability, while the ICC for the IGA (0.54)
indicated only fair reliability. The CVs for the oSCORAD and IGA were 28.1 and
33.0, respectively, indicating moderate variability. The CV for the EASI was
66.5, indicating high variability. CONCLUSION: Among the 3 compared scales, the
oSCORAD had the highest inter-rater reliability, whereas the EASI had the highest
intra-rater reliability. None of the 3 scoring methods showed a significant
advantage over the other. Thus, a reliable assessment of AD severity requires the
use of at least 2 independent measurements simultaneously.
PMID- 28494439
TI - Centromere Repositioning in Cattle (Bos taurus) Chromosome 17.
AB - Eukaryotic organisms have developed a structure, called centromere, able to
preserve the integrity of the genome during cell division. A young bull from the
Marchigiana breed, with a normal external phenotype, underwent routine
cytogenetic analysis to enter the reproduction center. All metaphases analyzed
showed an unusual biarmed chromosome of medium size despite a diploid set of
chromosomes (2n = 60,XY). FISH analysis excluded a pericentric inversion or a
reciprocal translocation, but highlighted a repositioning of the centromere in
BTA17. The satellite DNA was still in an acrocentric position. The telomeres were
normally present. The primary constriction on the abnormal chromosome was C-band
negative. Finally, the absence of a large genomic deletion in the BTA17
pericentromeric region was demonstrated by both array-CGH analysis and SNP array.
To our knowledge, this is the first case of centromere repositioning reported in
cattle.
PMID- 28494440
TI - Nuclear Architecture of Mouse Spermatocytes: Chromosome Topology,
Heterochromatin, and Nucleolus.
AB - The nuclear organization of spermatocytes in meiotic prophase I is primarily
determined by the synaptic organization of the bivalents that are bound by their
telomeres to the nuclear envelope and described as arc-shaped trajectories
through the 3D nuclear space. However, over this basic meiotic organization, a
spermatocyte nuclear architecture arises that is based on higher-ordered patterns
of spatial associations among chromosomal domains from different bivalents that
are conditioned by the individual characteristics of chromosomes and the
opportunity for interactions between their domains. Consequently, the nuclear
architecture is species-specific and prone to modification by chromosomal
rearrangements. This model is valid for the localization of any chromosomal
domain in the meiotic prophase nucleus. However, constitutive heterochromatin
plays a leading role in shaping nuclear territories. Thus, the nuclear
localization of nucleoli depends on the position of NORs in nucleolar bivalents,
but the association among nucleolar chromosomes mainly depends on the presence of
constitutive heterochromatin that does not affect the expression of the ribosomal
genes. Constitutive heterochromatin and nucleoli form complex nuclear territories
whose distribution in the nuclear space is nonrandom, supporting the hypothesis
regarding the existence of a species-specific nuclear architecture in first
meiotic prophase spermatocytes.
PMID- 28494441
TI - Different Successful Management Strategies for Obstructing Renal Parapelvic
Cysts.
AB - Parapelvic cysts originate in the renal parenchyma and extend into the renal
sinus. A series of 3 patients with symptomatic obstructing parapelvic cysts is
described, 2 with acute presentations, and 1 with chronic symptoms. In 2 of the 3
cases, there was a significant delay in establishing a diagnosis. Although one
individual was successfully managed by image-guided cyst aspiration, the second
patient required repeated aspiration due to cyst re-accumulation. A high index of
clinical suspicion and a combination of imaging modalities, including serial
ultrasound, excretory-phase CT, and MAG3 renogram, are necessary to establish the
diagnosis and monitor response to treatment.
PMID- 28494442
TI - Efficacy of Hyaluronic Acid/Carboxymethyl Cellulose-Based Bioresorbable Membranes
in Reducing Perihepatic Adhesion Formation: A Prospective Cohort Study.
AB - BACKGROUND: Perihepatic adhesions induced by hepatectomy make the subsequent
repeat hepatectomy technically demanding. The aim of this study was to verify the
effect of hyaluronic acid/carboxymethyl cellulose-based bioresorbable membrane
(HA membrane) in preventing posthepatectomy adhesion formation by focusing on the
ease of the adhesiolysis in subsequent hepatectomy for recurrent tumors. METHODS:
A total of 201 patients who underwent hepatectomy using HA membrane were
prospectively followed-up for 3 years. Thirty of the 201 patients underwent a
repeat hepatectomy for recurrence. The operative data of 85 cases of repeat
hepatectomy, the primary hepatectomy of which had been performed without the use
of HA membrane, served as the historical control data. The primary endpoint was
the time interval between the skin incision and the start of hepatic parenchymal
transection (the preparation time) including adhesiolysis. Secondary endpoints
were blood loss during the operation, incidence of postoperative complications,
and the biochemical data. RESULTS: The median preparation time (183 vs. 228 min;
p = 0.027) and total operation time (374 vs. 439 min; p = 0.041) were
significantly shorter in the HA membrane group than in the control group.
CONCLUSION: Use of HA membranes during hepatectomy enabled significant shortening
of the adhesiolysis time during the sequential hepatectomy performed for
recurrent tumors.
PMID- 28494443
TI - Short-Term Clinical and Oncological Outcomes after Single-Incision Plus One Port
Laparoscopic Anterior Resection for Rectal Cancer.
AB - AIM: In the past, we developed and reported single-incision plus one port
laparoscopic anterior resection (SILS + 1-AR) of the rectum. In this study, we
reviewed our experiences with 141 consecutive patients admitted in a community
hospital for undergoing SILS + 1-AR for rectal cancer and evaluated the short
term clinical and oncological outcomes. METHODS: A lap protector (LP) was
inserted through a 2.5 cm transumbilical incision; an EZ-access was mounted to
the LP and three 5-mm ports were placed. A 12-mm port was inserted in the right
lower quadrant. RESULTS: One hundred thirty-six patients (96.5%) completed their
treatment with SILA+1-AR. The number of tumor locations in the rectosigmoid,
rectum area above the peritoneal reflection (Ra), and rectum area below the
peritoneal reflection (Rb) were 44, 63, and 29 respectively. Six (5.6%) tumor
recurrences or metastasis occurred in 107 patients with stages I-III disease with
a median follow-up of 30 months. One patient with a positive surgical margin
rejected additional resection of the positive margin and died of recurrent
disease. CONCLUSION: Our initial experiences suggested that SILS + 1-AR is a
feasible and a safe treatment option for rectal cancer patients treated by
experienced surgeons specialized in SILS. However, further studies are needed to
demonstrate the advantages of this procedure compared to the benefits of
conventional laparoscopic AR.
PMID- 28494444
TI - Associations of Usual 24-Hour Sodium and Potassium Intakes with Blood Pressure
and Risk of Hypertension among Adults in China's Shandong and Jiangsu Provinces.
AB - BACKGROUND/AIMS: High sodium intake and low intake of potassium can increase
blood pressure (BP) and risk of developing hypertension. Few studies have
examined the association between 24-h urinary sodium and potassium excretion and
BP or risk of hypertension in China, and most used only a single 24-h urinary
sample. METHODS: We analyzed data on 2281 participants aged 18-69 years by using
two 24-h urinary sodium and potassium excretions from the supplemental baseline
survey of the Shandong-Ministry of Health Action on Salt Reduction and
Hypertension (SMASH) project. We used measurement error models to estimate usual
intakes, multivariable linear regression to assess their association with B P,
and logistic regression to estimate the risk of hypertension. RESULTS: The
average usual intakes of sodium and potassium, and the mean sodium-potassium
ratio, were 166.9 mmol/day, 25.3 mmol/day, and 6.8, respectively. All three
measures were significantly associated with systolic BP (SBP) and diastolic BP
(DBP), with an increase of 1.39 mmHg (95% confidence interval [CI] 0.44?2.34) in
SBP and 0.94 mmHg (95% CI 0.34?1.55) in DBP for a 1-standard deviation (SD)
(25.6mmol/day) increase in sodium intake, a decrease of 1.42 mmHg (95% CI -2.37?
0.47) in SBP and 0.91 mmHg (95% CI -1.52? -0.30) in DBP for a 1-SD (3.4 mmol/day)
increase in potassium intake, and an increase of 0.97 mmHg (95% CI 0.36?1.58) in
SBP and of 0.65 mmHg (95% CI 0.26?1.04) in DBP per unit increase in the sodium-to
potassium ratio. The adjusted odds ratios comparing the risk of hypertension
among adults in the highest with those in the lowest quintile differ
significantly for potassium (0.51; 95% CI 0.29?0.88) and sodium-to-potassium
ratio (1.40; 95% CI 1.01?1.94). CONCLUSIONS: Our results suggested that higher
sodium and lower potassium intakes are associated with increased BP and risk of
hypertension in the Shandong and Jiangsu adults.
PMID- 28494445
TI - Mechanisms of Improved Exercise Performance under Hyperoxia: On Haldane, Geppert,
Zunz, and Eschenbacher Transformations.
PMID- 28494446
TI - Mutation Load of Multiple Ion Channel Gene Mutations in Brugada Syndrome.
AB - Brugada syndrome is a primary arrhythmic syndrome that accounts for 20% of all
sudden cardiac death cases in individuals with a structurally normal heart.
Pathogenic variants associated with Brugada syndrome have been identified in over
19 genes, with SCN5A as a pivotal gene accounting for nearly 30% of cases. In
contrast to other arrhythmogenic channelopathies (such as long QT syndrome),
digenic inheritance has never been reported in Brugada syndrome. Exploring 66
cardiac genes using a new custom next-generation sequencing panel, we identified
a double heterozygosity for pathogenic mutations in SCN5A and TRPM4 in a Brugada
syndrome patient. The parents were heterozygous for each variation. This novel
finding highlights the role of mutation load in Brugada syndrome and strongly
suggests the adoption of a gene panel to obtain an accurate genetic diagnosis,
which is mandatory for risk stratification, prevention, and therapy.
PMID- 28494447
TI - Stromal Growth Differentiation Factor 15 and Its Association with Ovarian Cancer.
AB - BACKGROUND/AIMS: Growth differentiation factor 15 (GDF-15) is induced by pro
inflammatory cytokines. Higher levels of GDF-15 have been associated with
malignancy. The aim of the study was to evaluate both tissue and serum levels of
GDF-15 in ovarian neoplasms. METHODS: A cohort study evaluated 31 patients with
benign ovarian tumors and 34 patients with ovarian cancer were evaluated in 2
years. The inclusion criterion was histopathological diagnosis of ovarian
epithelial neoplasia. Exclusion criteria were secondary malignant ovarian
neoplasia and preoperative treatment. Serum and tissue levels of GDF-15 were
assessed by enzyme-linked immunosorbent assay and immunohistochemistry,
respectively. Chi-square test and unpaired t test were performed. RESULTS: Serum
levels were higher in the patients with malignant neoplasms than in the patients
with benign tumors, yet the difference was not statistically significant. GDF-15
immunostaining was significantly more frequent in the stroma of the malignant
tumors than in the stroma of the benign tumors (p = 0.0034). CONCLUSION: GDF-15
staining is elevated in the stroma of ovarian cancer, demonstrating that it may
be a potential diagnostic and therapeutic target.
PMID- 28494448
TI - Effects of CYP2C19 Variants on Fluoxetine Metabolism in vitro.
AB - AIMS: CYP2C19 is an important member of the cytochrome P450 enzyme superfamily.
We recently identified 31 CYP2C19 alleles in the Han Chinese population. The aim
of this study was to assess the catalytic activities of these allelic isoforms
and their effects on the metabolism of fluoxetine in vitro. METHODS: The wild
type and 30 CYP2C19 variants were expressed in insect cells and each variant was
characterized using fluoxetine as the substrate. Reactions were performed at 37
degrees C with 20-1,000 umol/L substrate for 30 min. By using ultra-high
performance liquid chromatography-mass spectrometry to detect the products, the
kinetic parameters Km, Vmax, and intrinsic clearance (Vmax/Km) of norfluoxetine
were determined. RESULTS: Among the CYP2C19 variants tested, T130M showed similar
intrinsic clearance (Vmax/Km) values with CYP2C19*1, while the intrinsic
clearance values of other variants were significantly decreased (from 9.56 to
77.77%). In addition, CYP2C19*3 and *35FS could not be detected because they have
no detectable enzyme activity. CONCLUSION: In China, the assessment of CYP2C19
variants in vitro offers valuable information relevant to the personalized
medicine for CYP2C19-metabolized drug.
PMID- 28494449
TI - Effect of the Serum Inhibited Gene (Si1) on Autophagy and Apoptosis in MCF-7
Breast Cancer Cells.
AB - BACKGROUND/AIMS: The serum inhibited gene (Si1) was named according to its
inhibited expression in response to serum exposure. Si1 has an important
relationship with tumors. Autophagy and apoptosis are two types of cell death.
However, there are few studies regarding the association between Si1 and
autophagy, or apoptosis in tumors. In this, we investigated the effect of Si1 on
the proliferation and cell cycle progression of MCF-7 cells and its influence on
autophagy and apoptosis in MCF-7 cells. METHODS: To investigate these functions
of Si1 in tumor cells, we firstly constructed a pEGFP-Si1 overexpression vector
and a pSilencer-Si1 interference vector, and we subsequently tested the
proliferation and cell cycle progression of MCF-7 cells using the MTT assay and
flow cytometry, and we then detected autophagy by western blotting and MDC
(Monodansylcadaverine) staining as well as apoptosis by western blotting and
Hoechst 33258 staining. RESULTS: We found that the Si1 gene can significantly
inhibit the viability of MCF-7 cells and arrest the cell cycle at the G2/M phase.
Si1 can induce autophagy through upregulation of LC3-II and Beclin1, it can
induce apoptosis through cleavage of PARP in MCF-7 cells. CONCLUSION: Altogether,
our study indicated that Si1 can inhibit cell proliferation of MCF-7, and also
induces autophagy and apoptosis. This study firstly investigated the effect of
Si1 on autophagy and apoptosis in MCF-7 cells. Moreover, it also improves the
current understanding of the mechanisms related to the effect of Si1 on tumor
cells and also provides a foundation for gene-targeted therapy.
PMID- 28494450
TI - Stachydrine Protects Against Pressure Overload-Induced Cardiac Hypertrophy by
Suppressing Autophagy.
AB - BACKGROUND: Autophagy is required for the maintenance of cardiomyocyte
homeostasis. However, excessive autophagy plays a maladaptive role in pressure
overload-induced heart failure. To identify mechanisms by which Stachydrine
inhibits pressure overload-induced cardiac hypertrophy, we determined inhibitory
activities against activation of NADPH oxidase, reactive oxygen species(ROS)
production and excessive activation of autophagy. METHODS: Stachydrine was
administered intragastrically to Wistar rats after Transverse aortic
constriction(TAC) and H9c2 cells were treated with Stachydrine after Angiotension
II stimulation. The activation of NADPH oxidase2 required the membrane
translocation of p47phox and p67phox. Cell membrane fraction was isolated by
ultracentrifuge in sucrose. The expression of p67phox, p47phox, gp91phox subunit
in the cell membrane were determined by western blot. The combination of p67phox
and gp91 phox subunit was detected by immunofluorescence staining. The expression
of phosphorylated p47phox subunit was determined by western blot. The
intracellular ROS were measured with DCF-DA fluoresence. The autophagic flux was
measured by recording the fluorescence emission of the fusion protein mRFP-GFP
LC3 by dynamic live-cell imaging. Reuslts: We report here that stachydrine, a
major constituent of Leonurus heterophyllus Sweet, inhibited AngII-induced
excessive autophagy within H9c2 cells. Stachydrine blocked the over
phosphorylation of the p47phox subunit, decreased the translocation of p47phox
and p67phox to the membrane, inhibited the activity of NOX2, and reduced the
generation of ROS. We also demonstrated that stachydrine ameliorated TAC-induced
cardiac hypertrophy, dysfunction and excessive autophagy in vivo. CONCLUSIONS:
Our study highlights the importance of regulating NOX2 when autophagy is
obviously activated. By inhibiting NOX2, Stachydrine inhibits ROS production,
thus exerting a remarkable activity of inhibiting hypertrophy, which could have
considerable effect on clinical practice.
PMID- 28494451
TI - Anthocyanins Prevent Colorectal Cancer Development in a Mouse Model.
AB - BACKGROUND: Colorectal cancer is the main leading cause of cancer-related deaths
worldwide. Present data suggest that plant-derived anthocyanins have anti
inflammatory and chemopreventive properties. This study was aimed at evaluating
the effect of an anthocyanin-rich extract from bilberries on colorectal tumour
development and growth in the administration of azoxymethan (AOM)/dextran sodium
sulfate (DSS) mouse model. METHODS: Colonic carcinogenesis was induced by AOM and
DSS 3 or 5%, respectively, in 50 female Balb/c mice. Mice received either normal
food (controls) or a diet containing either 10 or 1% anthocyanin-rich bilberry
extract. Colonoscopy took place at week 4 and 9 after initiation of
carcinogenesis. After termination at week 9, colon samples were analysed
macroscopically and microscopically. RESULTS: Mice receiving 10% anthocyanins
showed significantly (p < 0.004) less reduced colon length (12.1 cm [8.5-14.4
cm]) as compared to controls (11.2 cm [9.8-12.3]) indicating less inflammation.
Mice fed with 10% anthocyanin-rich extract revealed significantly less mean
tumour numbers (n = 1.2) compared to control (n = 14) and anthocyanin 1% treated
mice (n = 10.6, p < 0.001). CONCLUSION: Anthocyanins prevented the formation and
growth of colorectal cancer in AOM/DSS-treated Balb/c mice. Further studies
should investigate the mechanisms of how anthocyanins influence the development
of colorectal cancer.
PMID- 28494452
TI - The Novel Ser18del AVP Variant Causes Inherited Neurohypophyseal Diabetes
Insipidus by Mechanisms Shared with Other Signal Peptide Variants.
AB - BACKGROUND/AIM: Variability in the severity and age at onset of autosomal
dominant familial neurohypophyseal diabetes insipidus (adFNDI) may be associated
with certain types of variants in the arginine vasopressin (AVP) gene. In this
study, we aimed to describe a large family with an apparent predominant female
occurrence of polyuria and polydipsia and to determine the underlying cause.
METHODS: The family members reported their family demography and symptoms. Two
subjects were diagnosed by fluid deprivation and dDAVP challenge tests. Eight
subjects were tested genetically. The identified variant along with 3 previously
identified variants in the AVP gene were investigated by heterologous expression
in a human neuronal cell line (SH-SY5Y). RESULTS: Both subjects investigated
clinically had a partial neurohypophyseal diabetes insipidus phenotype. A
g.276_278delTCC variant in the AVP gene causing a Ser18del deletion in the signal
peptide (SP) of the AVP preprohormone was perfectly co-segregating with the
disease. When expressed in SH-SY5Y cells, the Ser18del variant along with 3 other
SP variants (g.227G>A, Ser17Phe, and Ala19Thr) resulted in reduced AVP mRNA,
impaired AVP secretion, and partial AVP prohormone degradation and retention in
the endoplasmic reticulum. Impaired SP cleavage was demonstrated directly in
cells expressing the Ser18del, g.227G>A, and Ala19Thr variants, using state-of
the-art mass spectrometry. CONCLUSION: Variants affecting the SP of the AVP
preprohormone cause adFNDI with variable phenotypes by a mechanism that may
involve impaired SP cleavage combined with effects at the mRNA, protein, and
cellular level.
PMID- 28494453
TI - The Peptidoglycan Recognition Proteins PGRPLA and PGRPLB Regulate Anopheles
Immunity to Bacteria and Affect Infection by Plasmodium.
AB - Peptidoglycan recognition proteins (PGRPs) form a family of immune regulators
that is conserved from insects to mammals. In the malaria vector mosquito
Anophelescoluzzii, the peptidoglycan receptor PGRPLC activates the immune
deficiency (Imd) pathway limiting both the microbiota load and Plasmodium
infection. Here, we carried out an RNA interference screen to examine the role of
all 7 Anopheles PGRPs in infections with Plasmodium berghei and P. falciparum. We
show that, in addition to PGRPLC, PGRPLA and PGRPS2/PGRPS3 also participate in
antiparasitic defenses, and that PGRPLB promotes mosquito permissiveness to P.
falciparum. We also demonstrate that following a mosquito blood feeding, which
promotes growth of the gut microbiota, PGRPLA and PGRPLB positively and
negatively regulate the activation of the Imd pathway, respectively. Our data
demonstrate that PGRPs are important regulators of the mosquito epithelial
immunity and vector competence.
PMID- 28494454
TI - Acceleration of Apoptosis by Extracellular Basic pH in a 3D Human Skin Equivalent
System.
AB - Previously, we have shown that extracellular basic pH plays a significant role in
both the direct and indirect regulation of cellular processes in a wound; this in
turn affects the wound-healing process. Several studies have demonstrated the
importance of apoptosis modulation in the wound-healing process, especially in
removing inflammatory cells and in inhibiting scar formation. However, the
effects of extracellular basic pH on wound healing-related skin damage are yet to
be examined. Therefore, we investigated the induction of accelerated apoptosis by
extracellular basic pH in skin. Apoptosis-related protein levels were measured
using an array kit, target protein expression levels were detected by
immunostaining, lactate dehydrogenase was analyzed spectrophotometrically, and
Annexin V levels were measured by fluorescence staining. Basic pH (8.40) strongly
upregulated extrinsic apoptosis proteins (Fas, high temperature requirement A,
and p21) and slightly upregulated intrinsic apoptosis proteins (cytochrome c, B
cell lymphoma 2 [Bcl-2], Bcl-2-associated death promoter, and Bcl-2-like protein
4) in a 3D human skin equivalent system. Moreover, basic pH (8.40) induced heat
shock protein (HSP) 60 and 70. In addition, basic pH-exposed Fas- and HSP60
knockdown cells showed significantly decreased levels of apoptosis. Taken
together, these results indicate that extracellular basic pH increases early
stage apoptosis through Fas/FasL via modulation of HSP60 and HSP70.
PMID- 28494455
TI - The Clinical Impact of Bet v 6 in Birch Pollen-Sensitized Patients.
AB - BACKGROUND: Bet v 6, a minor birch pollen allergen, is commercially available for
allergen-specific IgE antibody testing. However, there is hardly any literature
on the clinical impact of Bet v 6. The aim of the present study was to analyze if
testing specific IgE against Bet v 6 can add valuable benefit to the standard
diagnostics of birch pollen-sensitized patients, especially in patients with
unknown sensitization-eliciting allergens. METHODS: Birch pollen-sensitized
patients with missing IgE reactivity against Bet v 1, 2, and 4 were tested for
specific IgE antibodies against Bet v 6. For comparison, an equal number of
randomly selected patients with birch pollen sensitization, regardless of their
individual sensitization patterns, were tested for specific anti-Bet v 6.
RESULTS: Of 57 cases with missing reactivity against the standard birch pollen
allergens, 2 patients were positive for Bet v 6. In the representative sample, 3
patients showed specific IgE against Bet v 6 - resulting in a total prevalence of
5%. None of the Bet v 6-positive patients showed allergic symptoms after exposure
to birch pollen or an oral allergy syndrome. An increased prevalence of asthma
and a higher degree of sensitization were the only distinctive clinical features
in Bet v 6-positive patients. CONCLUSIONS: Among birch pollen-sensitized
patients, the prevalence of specific IgE against Bet v 6 is low. Further,
sensitization to Bet v 6, which shows characteristics of a panallergen, remains
clinically silent. Therefore, determination of anti-Bet v 6 is not considered
useful in the clinical routine.
PMID- 28494456
TI - Proton Magnetic Resonance Spectroscopy Study on the Metabolism Changes of
Cerebellum in Patients with Post-Stroke Depression.
AB - OBJECTIVE: To study the metabolic changes of cerebellum by proton magnetic
resonance Spectroscopy (1H-MRS) and discuss the relationships between the
cerebellar changes and depression severity in patients with post-stroke
depression. METHODS AND RESULTS: Data of demographic characteristics, individual
history and life style of all subjects were collected. 40 patients with stroke
and 20 controls were enrolled. All groups received T1WI, T2WI, DWI and 1H-MRS
examination. The cerebral infarction volume and the distribution and severity of
leukoaraiosis were evaluated. The ratios of NAA/Cr, Cho/Cr and Cho/NAA in the
cerebellum were calculated. There were no statistical significant difference in
the NAA/Cr, Cho/Cr and Cho/NAA ratios in bilateral cerebellum between CONT group
and NORM group. The Cho/Cr and Cho/NAA ratios in the cerebellum contralateral to
the stroke region were higher in PSD group than those in NORM and CONT groups,
and the Cho/Cr and Cho/NAA ratios in the cerebellum ipsilateral to the stroke
region were similar with those in NORM and CONT groups. However, there were no
statistical significant difference in the NAA/Cr ratios in bilateral cerebellum
among three groups. CONCLUSION: The result shows preliminarily that the
cerebellum involves in the development of post-stroke depression.
PMID- 28494457
TI - Resveratrol Protects Against Pulmonary Arterial Hypertension in Rats via
Activation of Silent Information Regulator 1.
AB - BACKGROUND/OBJECTIVES: The polyphenol resveratrol (Rev) has been found to exhibit
various beneficial effects including prevention of pulmonary arterial
hypertension (PAH). The present study was designed to investigate the action and
potential mechanism of Rev on PAH, focusing on the role of SIRT1 (Silent
Information Regulator 1) in apoptosis of pulmonary artery smooth muscle cells
(PASMCs). METHODS: PAH rats were established by exposure to hypoxia for 21 days.
Rev and SRT1720 (a selective SIRT1 activator) were used to reverse PAH by
gavaging rats. PASMCs were confronted with hypoxia for 24 h or 48 h and were then
treated with Rev or SRT1720 in vitro. Western blot was performed to detect the
protein expression of SIRT1. CCK-8 and scratch wound experiments were carried out
to verify cell proliferation. In addition, the TUNEL positive assay and flow
cytometry assay were used to measure PASMC apoptosis. Mitochondrial permeability
transition (mPT) was identified by confocal microscopy. Right ventricular
systolic pressure (RVSP) was determined with a Gould pressure transducer, and
right ventricular hypertrophy (RVH) was determined by weighing the cardiac
muscle. RESULTS: We demonstrated that Rev could reverse the remodelling of the
pulmonary vasculature, thus contributing to alleviating the severity of PAH. Down
regulation of SIRT1 was observed in PAH, but administration of Rev had no obvious
effect on the protein expression of SIRT1. In addition, Rev could induce
mitochondrial swelling and nuclear pyknosis, leading to small, dense, and
dysmorphic mitochondria in rats exposed to hypoxia alone. Rev treatment inhibited
PASMC proliferation in a dose-dependent manner in vitro. Incubation with SRT1720,
a specific activator of SIRT1, significantly retarded PASMC proliferation and
promoted PASMC apoptosis in vitro. The mechanism could be associated with
inducing mPT damage in PASMCs. Rev and SRT1720 treatment mitigated RVSP and
reduced RVH. CONCLUSION: Rev produced a beneficial effect partially by enhancing
the activation of SIRT1, thus improving RVSP and reducing RVH. SIRT1 activation
increased PASMC apoptosis by inducing mPT dysfunction, which might be a novel
future strategy for the treatment of PAH.
PMID- 28494458
TI - Improvement of Anal Function by Adipose-Derived Stem Cell Sheets.
AB - AIM: One of the most troublesome complications of anal preserving surgery is anal
sphincter dysfunction. The aim of this study was to evaluate functional recovery
after implantation of adipose-derived stem cell (ADSC) sheets, novel
biotechnology, for an anal sphincter resection animal model. METHODS: Eighteen
female Sprague-Dawley rats underwent removal of the nearest half of the internal
and external anal sphincter muscle. Nine rats received transplantation with ADSC
sheets to the resected area while the remaining rats received no transplantation.
The rats were evaluated for the anal function by measuring their resting pressure
before surgery and on postoperative days 1, 7, 14, 28, and 56. In addition, the
rats were examined for the presence of smooth muscle and also to determine its
origin. RESULTS: The improvement of the anal pressure was significantly greater
in the ADSC sheet transplantation group compared with the control group.
Histologically, at the vicinity of the remaining smooth muscle, reproduction of
smooth muscle was detected. Using in fluorescence in situ hybridization, the
cells were shown to be from the recipient. CONCLUSION: Regenerative therapy using
ADSC sheet has the potential to recover anal sphincter dysfunction due to
anorectal surgery.
PMID- 28494459
TI - Influence of Bovine Serum Lipids and Fetal Bovine Serum on the Expression of Cell
Surface Markers in Cultured Bovine Preadipocytes.
AB - To establish the influence of fetal bovine serum (FBS) and bovine serum lipids
(BSL) on cell differentiation marker expression, bovine adipose-derived stem
cells from subcutaneous tissue were incubated for 14 days in 4 types of
differentiation media containing 10% FBS and 10 uL/mL BSL (TRT-1), no FBS and 10
uL/mL of BSL (TRT-2), 10% FBS and no BSL (TRT-3), or no supplements (TRT-4).
Cells were subjected to Nile red staining, immunocytochemistry (CD73, CD90,
CD105, DLK1, FabP4), and quantitative real-time PCR (CD73, CD90, CD105, FabP4).
The number of cells presenting FabP4 and the percentage of mature adipocytes with
large lipid droplets were increased in TRT-2, accompanied by a robust increase in
FabP4 mRNA abundance and a decrease in DLK1-positive cells. In preadipocytes,
CD73 was present around the nucleus and translocated towards cell membranes
during differentiation. Although the percentage of CD73-positive cells was not
different among treatments, its mRNA abundance, immunocytochemical staining
intensity, and translocation towards cell membranes were decreased when the
medium contained no FBS (TRT-2 and TRT-4). All cells showed a diffuse
distribution of CD90 and CD105 and remained positive for these markers
irrespective of the treatment. However, the CD90 and CD105 mRNA abundance was
decreased in TRT-2 and TRT-4; i.e., in media containing no FBS. The presence of
FBS increased the absolute number of cell nuclei as assessed by DAPI
fluorescence. Our results suggest that bovine subcutaneous preadipocytes display
typical stem cell markers. The differentiation into mature adipocytes is promoted
by BSL, whereas FBS endorses cell proliferation.
PMID- 28494460
TI - Persistently Altered Metabolic Phenotype following Perinatal Excitotoxic Brain
Injury.
AB - Excitotoxicity plays a key role during insults to the developing brain such as
neonatal encephalopathy, stroke, and encephalopathy of prematurity. Such insults
affect many thousands of infants each year. Excitotoxicity causes frank lesions
due to cell death and gliosis and disturbs normal developmental process, leading
to deficits in learning, memory, and social integration that persist into
adulthood. Understanding the underlying processes of the acute effects of
excitotoxicity and its persistence during brain maturation provides an
opportunity to identify mechanistic or diagnostic biomarkers, thus enabling and
designing possible therapies. We applied mass spectrometry to provide metabolic
profiles of brain tissue and plasma over time following an excitotoxic lesion
(intracerebral ibotenate) to the neonatal (postnatal day 5) mouse brain. We found
no differences between the plasma from the control (PBS-injected) and excitotoxic
(ibotenate-injected) groups over time (on postnatal days 8, 9, 10, and 30). In
the brain, we found that variations in amino acids (arginine, glutamine,
phenylananine, and proline) and glycerophospholipids were sustaining acute and
delayed (tertiary) responses to injury. In particular, the effect of the
excitotoxic lesion on the normal profile of development was linked to alterations
in a fingerprint of glycerophospolipids and amino acids. Specifically, we
identified increases in the amino acids glutamine, proline, serine, threonine,
tryptophan, valine, and the sphingolipid SM C26:1, and decreases in the
glycerophospholipids, i.e., the arachidonic acid-containing phosphatidylcholine
(PC aa) C30:2 and the PC aa C32:3. This study demonstrates that metabolic
profiling is a useful approach to identify acute and tertiary effects in an
excitotoxic lesion model, and generating a short list of targets with future
potential in the hunt for identification, stratification, and possibly therapy.
PMID- 28494461
TI - Accuracy of Pancreatic Neuroendocrine Tumour Grading by Endoscopic Ultrasound
Guided Fine Needle Aspiration: Analysis of a Large Cohort and Perspectives for
Improvement.
AB - INTRODUCTION: Since the WHO Classification of Tumours of the Digestive System has
been published in 2010, resected pancreatic neuroendocrine tumours (pNETs) are
graded as grade 1 (G1), grade 2 (G2) or grade 3 (G3) using the Ki67 labelling
index (Ki67-LI). Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is
often used for diagnosis, but few studies have assessed its value for grading.
AIMS: The aims of this study were to compare the Ki67-LI obtained by cytological
grading (cG) with that obtained by histological grading (hG) and to assess (1)
the influence of tumour size and the number of counted cells on FNA grading as
well as (2) the overall survival (OS) and progression-free survival based on cG.
MATERIALS AND METHODS: EUS-FNA was performed for 102 pNETs (57 resected). cG (200
cells counted) was done on all FNAs. For 29 FNAs, >2,000 cells were counted (14
resected). A comparison was made between hG and cG for the 57 resected patients.
Patients were followed up until June 2016. RESULTS: cG was consistent with hG in
39 of 57 patients with a concordance rate of 72% using a Ki67-LI cut-off of 5%
for G1/G2. For Ki67-LI absolute values, the correlation was r = 0.443 and
increased to r = 0.824 (p < 0.001) when only FNAs with >2,000 cells were counted.
Twenty-one of 22 pNETs <2 cm had the same grading on cG and hG, whereas grading
was discordant for 15 of 16 pNETs >2 cm. Thirty-eight patients died after 70.5
months of follow-up. OS for the whole cohort was 235 months and differed between
cG1 (235 months), cG2 (36.3 months) and cG3 (10.9 months). CONCLUSION: cG of
pNETs is more accurate when tumours measure <2 cm and more cells are counted on
FNA. Discrepancies are seen between G2 tumours which are often considered G1 on
FNA due to tumour heterogeneity. EUS-FNA is valuable to distinguish between
patients with good (cG1) and poor (cG3) prognosis.
PMID- 28494462
TI - In vitro Growth Pattern of Primary Human Osteoblasts on Calcium Phosphate- and
Polymethylmethacrylate-Based Bone Cement.
AB - BACKGROUND/PURPOSE: Polymethylmethacrylate (PMMA) and calcium phosphate (Ca-P)
cements are widely used for arthroplasty surgery and augmentation of bone
defects. However, aseptic implant loosening in absence of wear-induced osteolysis
indicates an unfavourable interaction between the cement surface and human
osteoblasts. Our underlying hypothesis is that cement surfaces directly modify
cell viability, proliferation rate, and cell differentiation. METHODS: To test
this hypothesis, we examined primary human osteoblasts harvested from six
individuals. These cells were pooled and subsequently seeded directly on cement
pellets prepared from Palacos(r) R, Palacos(r) R+G, and Norian(r) Drillable
cements. After incubation for 24 and 72 h, cell viability, proliferation rate,
apoptosis rate, and cell differentiation were analysed. RESULTS: Upon cultivation
of human osteoblasts on cement surfaces, we observed a significantly reduced cell
viability and DNA content compared to the control. Analysis of the apoptosis rate
revealed an increase for cells on Palacos R and Norian Drillable, but a
significant decrease on Palacos R+G compared to the control. Regarding osteogenic
differentiation, significantly lower values of alkaline phosphatase enzyme
activity were identified for all cement surfaces after 24 and 72 h compared to
cultivation on tissue culture plastic, serving as control. CONCLUSIONS: In
summary, these data suggest a limited biocompatibility of both PMMA and Ca-P
cements, necessitating further research to reduce unfavourable cell-cement
interactions and consequently extend implant survival.
PMID- 28494463
TI - Plasma Drug Concentrations in Patients with Pulmonary Arterial Hypertension on
Combination Treatment.
AB - BACKGROUND: Combination therapy with the phosphodiesterase type 5 inhibitors (PDE
5i) sildenafil or tadalafil and the endothelin receptor antagonists (ERA)
bosentan, ambrisentan, or macitentan may cause mutual pharmacokinetic
interactions in patients with pulmonary arterial hypertension (PAH). OBJECTIVE:
The objective of this study was to analyze plasma drug concentrations in PAH
patients receiving different combination treatments. METHODS: PAH patients
receiving a stable combination treatment with ERA and PDE-5i with targeted dosage
for at least 1 month were routinely assessed, including clinical parameters and
plasma drug concentrations. Concentrations were normalized considering dose and
time from last medication intake and presented as multiples of the expected mean
(MoM) of the respective monotherapies. RESULTS: A total of 125 PAH patients (84
female, 41 male, 57% idiopathic/heritable) were included. Sildenafil and
tadalafil concentrations were lowest in combination with bosentan (MoM 0.44 +/-
0.42, 95% confidence interval [CI] 0.30-0.57, and MoM 0.89 +/- 0.53, 95% CI 0.50
1.28, respectively) compared to the combination with ambrisentan (MoM 1.3 +/-
0.97, 95% CI 0.86-1.73, and MoM 1.67 +/- 0.63, 95% CI 1.40-1.94, respectively)
and macitentan (MoM 1.16 +/- 0.87, 95% CI 0.86-1.46, and MoM 1.59 +/- 0.99, 95%
CI 0.80-2.38, respectively). The combination of sildenafil and bosentan led to
more than twice the expected bosentan concentrations in 53.8%. Patients switching
from sildenafil-bosentan to macitentan showed a significant increase in
sildenafil concentrations (p < 0.001). CONCLUSIONS: Only the combination with
macitentan or ambrisentan led to targeted mean PDE-5i plasma concentrations and
should therefore be preferred to combination with bosentan. Sildenafil-bosentan
showed the strongest interaction, with low sildenafil and high bosentan
concentrations. The study was not powered to analyze whether lower PDE-5i
concentrations cause unsatisfying clinical response. However, plasma
concentrations within a targeted range are desirable and may become of increasing
importance.
PMID- 28494464
TI - Immunoregulatory Role of MicroRNA-21 in Macrophages in Response to Bacillus
Calmette-Guerin Infection Involves Modulation of the TLR4/MyD88 Signaling
Pathway.
AB - BACKGROUND/AIMS: The purpose of this study is to explore the immunoregulatory
role of microRNA-21 (miR-21) targeting of the TLR4/MyD88 signaling pathway in
macrophages in response to Bacillus Calmette-Guerin (BCG) infection. METHODS:
After infection with BCG, mouse RAW246.7 cells were assigned into control, BCG,
miR-21 mimic + BCG, mimic-negative control (NC) + BCG, miR-21 inhibitor + BCG,
inhibitor-NC + BCG, BCG + TAK242 (an inhibitor of the TLR4 signaling pathway),
and miR-21 inhibitor + TAK242 + BCG groups. Western blotting and qRT-PCR were
used to detect the expression of miR-21, TLR4 and MyD88. The levels of TNF-a, IL
6 and IL-10 were detected by enzyme-linked immunosorbent assay (ELISA). Cell
viability was measured using an MTT assay. Cell apoptosis and necrosis rates were
detected using flow cytometry. RESULTS: Compared with the control group, miR-21
expression and levels of TNF-a, IL-6 and IL-10, as well as cell apoptosis and
necrosis rates, were elevated, while expression of TLR4 and MyD88, as well as
cell viability, were reduced in BCG infection groups. Compared with the BCG
group, miR-21 expression was increased in the miR-21 mimic + BCG group but
decreased in the miR-21 inhibitor + BCG and miR-21 inhibitor + TAK242 + BCG
groups. The expression of TLR4 and MyD88, as well as the cell viability, were
decreased, while levels of TNF-a, IL-6 and IL-10, as well as cell apoptosis and
necrosis rates, were increased in the miR-21 mimic + BCG and TAK242 + BCG groups.
The opposite trends were found in the miR-21 inhibitor + BCG group. Compared with
the TAK242 + BCG group, the miR-21 inhibitor + TAK242 + BCG group had higher
expression of TLR4 and MyD88 as well as higher cell viability and lower levels of
TNF-a, IL-6, IL-10, cell apoptosis and necrosis rates. However, the miR-21
inhibitor + TAK242 + BCG group exhibited the opposite trends when compared with
the miR-21 inhibitor + BCG group. CONCLUSION: Our results suggest that miR-21 can
negatively modulate the TLR4/MyD88 signaling pathway, resulting in decreased cell
viability, increased cell apoptosis and increased levels of inflammatory factors
following BCG infection in macrophages.
PMID- 28494465
TI - Congenital Salivary Gland Anlage Tumor: An Unusual Anterior Skull Base Mass in
the Neonatal Period.
AB - Congenital salivary gland anlage tumor (SGAT) is a benign nasopharyngeal mass
that presents with respiratory distress in infancy. Prior case reports have
characterized SGAT as a lesion of the nasopharynx without intracranial extension.
We report a unique case of SGAT extending through the anterior skull base and
discuss the differential diagnosis and management of this unusual entity.
PMID- 28494466
TI - Let-7a Inhibits T-Cell Proliferation and IFN-gamma Secretion by Down-Regulating
STAT3 Expression in Patients with Psoriasis.
AB - OBJECTIVE: This study aimed to explore the effects of STAT3 targeting by let-7a
on T-cell proliferation and IFN-gamma secretion in psoriasis. METHODS: From
January 2013 to January 2015, 40 patients with psoriasis (psoriasis group) and 38
volunteers undergoing plastic surgery (control group) were enrolled in this
study. Pearson correlation analysis was performed to evaluate the correlation
between let-7a and STAT3 expression. T-cells were isolated and subjected to
different transfection methods. A dual luciferase reporter assay was carried out
to confirm STAT3 as a target gene of let-7a. Let-7a, STAT3 and IFN-gamma mRNA
expression was detected by quantitative real-time fluorescent polymerase chain
reaction (qRT-PCR), and pSTAT3 protein levels were determined by Western blot. T
cell proliferation was evaluated with a cell counting kit-8 (CCK-8) assay.
RESULTS: The level of STAT3 mRNA and pSTAT3 was higher, but let-7a expression was
lower in the psoriasis group than the control group. Pearson correlation analysis
indicated that STAT3 expression was negatively correlated with let-7a expression.
T-cells transfected with inhibitors exhibited greater IFN-gamma mRNA expression
and T-cell proliferation than transfected T-cells and T-cells transfected with a
non-sense sequence, while T-cells transfected with let-7a mimics exhibited lower
IFN-gamma mRNA expression and T-cell proliferation than transfected T-cells and T
cells transfected with a non-sense sequence. This suggested that siRNA-STAT3
could reverse the increase in IFN-y mRNA expression and T-cell proliferation
induced by let-7a inhibitors. CONCLUSION: Our results demonstrated that let-7a
inhibits T-cell proliferation and IFN-gamma secretion by down-regulating STAT3 in
psoriasis.
PMID- 28494467
TI - Expression and Characterization of Functional Recombinant Bet v 1.0101 in the
Chloroplast of Chlamydomonas reinhardtii.
AB - BACKGROUND: Allergen immunotherapy (AIT) still plays a minor role in the
treatment of allergic diseases. To improve the acceptance of AIT by allergic
patients, the treatment has to become more convenient and efficacious. One
possibility is the oral application of allergens or derivatives thereof.
Therefore, we sought to produce a recombinant allergen in the green alga
Chlamydomonas reinhardtii as a novel production platform. METHODS: The major
birch pollen allergen Bet v 1 was selected as candidate molecule, and a codon
optimized gene was synthesized and stably integrated into the microalga C.
reinhardtii FUD50. Positive transformants were identified by PCR, cultured, and
thereafter cells were disrupted by sonication. Bet v 1 was purified from algal
total soluble protein (TSP) by affinity chromatography and characterized
physicochemically as well as immunologically. RESULTS: All transformants showed
expression of the allergen with yields between 0.01 and 0.04% of TSP. Algal
derived Bet v 1 displayed similar secondary structure elements as the Escherichia
coli-produced reference allergen. Moreover, Bet v 1 produced in C. reinhardtii
showed binding comparable to human IgE as well as murine Bet v 1-specific IgG.
CONCLUSION: We could successfully produce recombinant Bet v 1 in C. reinhardtii.
As microalgae are classified as GRAS (generally recognized as safe), the pilot
study supports the development of novel allergy treatment concepts such as the
oral administration of allergen-containing algal extracts for therapy.
PMID- 28494468
TI - Genes Involved in Neurodevelopment, Neuroplasticity, and Bipolar Disorder:
CACNA1C, CHRNA1, and MAPK1.
AB - BACKGROUND: Bipolar disorder (BPD) is a common and severe mental disorder. The
involvement of genetic factors in the pathophysiology of BPD is well known. In
the present study, we tested the association of several single-nucleotide
polymorphisms (SNPs) within 3 strong candidate genes (CACNA1C, CHRNA7, and MAPK1)
with BPD. These genes are involved in monoamine-related pathways, as well as in
dendrite development, neuronal survival, synaptic plasticity, and
memory/learning. METHODS: One hundred and thirty-two subjects diagnosed with BPD
and 326 healthy controls of Korean ancestry were genotyped for 40 SNPs within
CACNA1C, CHRNA17, and MAPK1. Distribution of alleles and block of haplotypes
within each gene were compared in cases and controls. Interactions between
variants in different loci were also tested. RESULTS: Significant differences in
the distribution of alleles between the cases and controls were detected for
rs1016388 within CACNA1C, rs1514250, rs2337980, rs6494223, rs3826029 and
rs4779565 within CHRNA7, and rs8136867 within MAPK1. Haplotype analyses also
confirmed an involvement of variations within these genes in BPD. Finally,
exploratory epistatic analyses demonstrated potential interactive effects,
especially regarding variations in CACNA1C and CHRNA7. LIMITATIONS: Limited
sample size and risk of false-positive findings. DISCUSSION: Our data suggest a
possible role of these 3 genes in BPD. Alterations of 1 or more common brain
pathways (e.g., neurodevelopment and neuroplasticity, calcium signaling) may
explain the obtained results.
PMID- 28494470
TI - Comorbid conditions delay diagnosis of colorectal cancer: a cohort study using
electronic primary care records.
AB - BACKGROUND: Pre-existing non-cancer conditions may complicate and delay
colorectal cancer diagnosis. METHOD: Incident cases (aged ?40 years, 2007-2009)
with colorectal cancer were identified in the Clinical Practice Research
Datalink, UK. Diagnostic interval was defined as time from first symptomatic
presentation of colorectal cancer to diagnosis. Comorbid conditions were
classified as 'competing demands' (unrelated to colorectal cancer) or
'alternative explanations' (sharing symptoms with colorectal cancer). The
association between diagnostic interval (log-transformed) and age, gender,
consultation rate and number of comorbid conditions was investigated using linear
regressions, reported using geometric means. RESULTS: Out of the 4512 patients
included, 72.9% had ?1 competing demand and 31.3% had ?1 alternative explanation.
In the regression model, the numbers of both types of comorbid conditions were
independently associated with longer diagnostic interval: a single competing
demand delayed diagnosis by 10 days, and four or more by 32 days; and a single
alternative explanation by 9 days. For individual conditions, the longest delay
was observed for inflammatory bowel disease (26 days; 95% CI 14-39). CONCLUSIONS:
The burden and nature of comorbidity is associated with delayed diagnosis in
colorectal cancer, particularly in patients aged ?80 years. Effective clinical
strategies are needed for shortening diagnostic interval in patients with
comorbidity.
PMID- 28494469
TI - Mutation status among patients with sinonasal mucosal melanoma and its impact on
survival.
AB - BACKGROUND: Sinonasal mucosal melanoma (SNMM) comprises <1% of all melanomas and
lacks well-characterised molecular markers. Our aim was to determine the
frequencies of common mutations and examine their utility as molecular markers in
a large series of primary SNMMs. METHODS: SNMM patients seen at our institution
from August 1991 through July 2016 were identified. Genomic DNA was extracted
from 66 formalin-fixed paraffin-embedded tumours and screened for mutations by
direct sequencing. We investigated the association of mutations with
clinicopathological features and survival outcomes. RESULTS: Overall, 41% (27 out
of 66) of the SNMMs harboured mutations. BRAF and KIT mutations were identified
in 8% (five patients) and 5% (three patients) of SNMMs, respectively, whereas
NRAS mutations were detected in 30% (20 patients) of SNMMs. Mutation rates in
these oncogenes were similar between SNMMs located in the paranasal sinuses and
those in the nasal cavity (30% and 13%, respectively, P=0.09). In a multivariate
analysis, patients with negative margins had significantly better overall
survival (hazard ratio 5.43, 95% confidence interval 1.44-21.85, P=0.01) and
disease-specific survival (hazard ratio 21.9, 95% confidence interval 3.71-180,
P=0.0004). The mutation status of the tumours showed no association with survival
outcomes. CONCLUSIONS: In SNNM, mutation status does not affect survival
outcomes, but NRAS mutations are relatively frequent and could be targeted in
this disease by MEK inhibitors.
PMID- 28494472
TI - A tale of two islands-trauma care in New Zealand.
PMID- 28494473
TI - Improving outcomes in orthopaedic care.
PMID- 28494471
TI - Inhibition of neurotensin receptor 1 induces intrinsic apoptosis via let-7a
3p/Bcl-w axis in glioblastoma.
AB - : Backgroud:Glioblastoma is a kind of highly malignant and aggressive tumours in
the central nervous system. Previously, we found that neurotensin (NTS) and its
high-affinity receptor 1 (NTSR1) had essential roles in cell proliferation and
invasiveness of glioblastoma. Unexpectedly, cell death also appeared by
inhibition of NTSR1 except for cell cycle arrest. However, the mechanisms were
remained to be further explored. METHODS: Cells treated with SR48692, a selective
antagonist of NTSR1, or NTSR1 shRNA were stained with Annexin V-FITC/PI and the
apoptosis was assessed by flow cytometry. Cytochrome c release was detected by
using immunofluorescence. Mitochondrial membrane potential (MMP, DeltaPsim) loss
was stained by JC-1 and detected by immunofluorescence or flow cytometry.
Apoptosis antibody array and microRNA microarray were performed to seek the
potential regulators of NTSR1 inhibition-induced apoptosis. Interaction between
let-7a-3p and Bcl-w 3'UTR was evaluated by using luciferase assay. RESULTS:
SR48692 induced massive apoptosis, which was related to mitochondrial cytochrome
c release and MMP loss. Knockdown of NTSR1 induced slight apoptosis and
significant MMP loss. In addition, NTSR1 inhibition sensitised glioblastoma cells
to actinomycin D or doxorubicin-induced apoptosis. Consistently, NTSR1 inhibition
induced mitochondrial apoptosis was accompanied by downregulation of Bcl-w and
Bcl-2. Restoration of Bcl-w partly rescued NTSR1 deficiency-induced apoptosis. In
addition, NTSR1 deficiency promoted higher let-7a-3p expression and inhibition
let-7a-3p partly rescued NTSR1 inhibition-induced apoptosis. In addition, let-7a
3p inhibition promoted 3'UTR activities of Bcl-w and the expression of c-Myc and
LIN28, which were the upstream of let-7a-3p, decreased after NTSR1 inhibition.
CONCLUSIONS: NTSR1 had an important role in protecting glioblastoma from
intrinsic apoptosis via c-Myc/LIN28/let-7a-3p/Bcl-w axis.
PMID- 28494474
TI - The 'six hour target' in New Zealand is associated with reduced mortality and
greater efficiency.
PMID- 28494475
TI - Impact of a national time target for ED length of stay on patient outcomes.
AB - AIM: The impact of national targets for emergency department (ED) length of stay
(LOS) on patient care is unclear. This study aimed to determine the effect of New
Zealand's six-hour time target (95% of ED patients discharged or admitted to
hospital within six hours) on a range of quality indicators. METHODS: A
nationwide observational study from 2006 to 2012 modelled differences in changes
over time before and after target introduction in 2009. The observed model
estimates in 2012 were compared to those predicted if pre-target trends had
continued. Differences are absolute values except for morality, which is
presented as a relative change. RESULTS: There were 5,793,767 ED presentations
and 2,082,374 elective admissions from 18 out of a possible 20 district health
boards included in the study. There were clinically important reductions in
hospital LOS (-0.29 days), EDLOS (-1.1 hours), admitted patients EDLOS (-2.9
hours), ED crowding (-26.8%), ED mortality (-57.8%), elective inpatient mortality
(-42.2%) and the proportion not waiting for assessment (-2.8%). Small changes
were seen in time to assessment in the ED (-3.4 minutes), re-presentation to ED
within 48 hours of the index ED discharge (-0.7%), re-presentation to ED within
48 hours from ward discharge (+0.4%) and acute admissions (+3.9%). An increase
was observed in re-admission to a ward within 30 days of discharge (1.0%). These
changes were all statistically significant (p<0.001). CONCLUSION: Most outcomes
we investigated either improved or were unchanged after the introduction of the
time target policy in New Zealand. However, attention is required to ensure that
reductions in hospital length of stay are not at the expense of subsequent re
admissions.
PMID- 28494476
TI - Effect of the Shorter Stays in Emergency Departments time target policy on key
indicators of quality of care.
AB - AIM: To determine whether implementation of a national health target called
Shorter Stays in Emergency Departments impacted on clinical markers of quality of
care. METHOD: A retrospective pre- and post-intervention study from 2006 to 2012
examined quality of care metrics for five different indicators at different sites
in relation to the implementation of the target using a general linear model for
times to treatment. Explanatory variables included period (pre- or post-target),
ethnicity, age, deprivation and severity of condition. Back transformed least
square means were used to describe the outcomes. RESULTS: The times to treatment
for ST elevation myocardial infarction; 36.9 (28-49) vs 47.6 (36-63) minutes
p=0.14, antibiotics for severe sepsis; 105.9 (73-153) vs 104.3 (70-155) minutes
p=0.93, analgesia for moderate or severe pain; 48 (31-75) vs 46 (32-66) minutes p
=0.77, theatre for fractured neck of femur; 35.4 (32.1-39.1) vs 32.4 (29.2-36.1)
hours, and to theatre for appendicitis; 14.1 (12-17) vs 16.4 (14-20) hours were
unchanged after implementation of the target. Treatment adequacy was also
unchanged for these indicators. CONCLUSION: Introduction of the Shorter Stays in
Emergency Departments target was not associated with any clinically important or
statistically significant changes in the time to treatment and adequacy of care
for five different clinical indicators of quality of care in Aotearoa New
Zealand. For those indicators measured at one site only, it is unknown whether
these results can be generalised to other sites.
PMID- 28494477
TI - New Zealand plastic surgeons' life-time contribution to peer-reviewed literature.
AB - AIM: The New Zealand Medical Association commits the New Zealand doctor to
evidence-based medicine, scholarship, teaching, collaboration and communication.
To assess this commitment, one measure, contribution to the peer-reviewed
literature, was examined for one group of New Zealand doctors: plastic surgeons.
METHOD: Plastic surgeons with a current practising certificate were identified on
the New Zealand medical register (April 2016). Scopus database was searched for
publications by each. RESULTS: Sixty-five surgeons authored 541 unique items in
134 journals, generating 8,047 citations. Between medical graduation and
specialty qualification, a mean 1.8 items were published per practitioner (range
0-11). Twenty-three practitioners (35.4%) did not publish during this time.
Between specialty qualification and the end of 2015, mean number of items
published per surgeon was 7.3 (range 0-97). Thirteen (20.0%) surgeons had not
published since specialist qualification. The general trend was for surgeons to
become less productive with increasing time in practice. Mean surgeon h-index was
4.4 (range 0-26). Four surgeons (6.2%) had not published at any time. CONCLUSION:
As a group, but with exceptions and less so in later practice, New Zealand
plastic surgeons would seem to demonstrate commitment to evidence-based medicine,
scholarship, teaching, collaboration and communication expected of a New Zealand
doctor, as evidenced by peer-review publication.
PMID- 28494478
TI - Survival of Legionella in earthquake-induced soil disturbance (liquefaction) in
residential areas, Christchurch, New Zealand: implications for disease.
AB - AIM: To investigate a possible link between liquefaction dust exposure and the
noticeable increase in legionellosis cases in response to major earthquakes in
2010 and 2011 that resulted in widespread soil disturbance (liquefaction) in
parts of Christchurch, New Zealand. METHOD: We culture tested liquefaction
affected soil for Legionella spp. in the six months following the first
earthquake in 2010. Thirty silt samples were collected randomly from locations
within Christchurch's metropolitan area that were affected by liquefaction. The
samples were tested to determine the presence of Legionella using qualitative and
quantitative methods. Liquefaction-affected soil samples from three sites were
further subjected to particle size distribution analysis and determination of
major oxides. A controlled field study was established using six silt samples and
one control (commercial compost), seeded with a wild-type strain of Legionella
bozemanae serogroup (sg) 1 and persistence monitored over a 60-day period by
culturing for the presence of Legionella. Dry matter determinations were
undertaken so that total Legionella could be calculated on a dry weight basis.
RESULTS: Legionella bacteria were undetectable after day one in the silt samples.
However, L. bozemanae sg1 was detected in the control sample for the entire study
period. CONCLUSION: This study showed that the liquefaction-affected soil could
not contribute directly to the observed increase in legionellosis cases after the
earthquakes due to its inability to support growth and survival of the Legionella
bacteria.
PMID- 28494479
TI - A walking stick in one hand and a chainsaw in the other: patients' perspectives
of living with multimorbidity.
AB - AIMS: Multimorbidity is common, yet there are major gaps in research,
particularly among younger and indigenous populations. This research aimed to
understand patients' perspectives of living with multimorbidity. METHODS: A
qualitative study of 61 people living with multimorbidity, 27 of whom were Maori
and a third aged under 65, from urban and rural regions in New Zealand. Six focus
groups and 14 interviews were conducted, recorded, transcribed and analysed.
RESULTS: For many participants, living with multimorbidity disrupted their
'normal' lives, posing challenges in everyday activities such as eating and
toileting, working and managing medications. Dealing with the health system posed
challenges such as accessing appointments and having enough time in
consultations. Cultural competency, good communication and continuity of care
from healthcare providers were all valued. Participants had many recommendations
to improve management, including a professional single point of contact to
coordinate all specialist care. CONCLUSIONS: Living with multimorbidity is often
challenging requiring people to manage their conditions while continuing to live
their lives. This research suggests changes are needed in the health system in
New Zealand and elsewhere to better manage multimorbidity thus improving
patient's lives and reducing costs to the health sector and wider society.
PMID- 28494480
TI - Implementation and effects of Enhanced Recovery After Surgery for hip and knee
replacements and fractured neck of femur in New Zealand orthopaedic services.
AB - AIM: The National Orthopaedic Enhanced Recovery After Surgery (ERAS)
Collaborative was launched in November 2013 to implement ERAS protocols for hip
and knee total joint arthroplasty (TJA) and fractured neck of femur (NOF) in
participating district health boards (DHBs) by December 2014. This paper reports
on the results. METHOD: ERAS protocols were developed for hip and knee TJA and
fractured NOF. Breakthrough Series collaborative methodology was used to
implement the ERAS protocols in 18 DHBs. We collected monthly data on compliance
with protocols and average length of stay (ALOS). Data were analysed using run
charts and Shewhart control charts. RESULTS: The national percentage of ERAS
components achieved across all DHBs rose from 33% to 75% on the elective knee TJA
pathway, from 31% to 78% on the elective hip TJA pathway and from 29% to 51% on
the acute fractured NOF pathway. The ALOS for knee TJA reduced from 5.4 days to
4.5 days. The ALOS for hip TJA reduced from 5.1 days to 4.3 days. There was no
change in the ALOS for fractured NOF. CONCLUSION: The National Orthopaedic ERAS
Collaborative increased uptake of ERAS protocols across all three pathways and
decreased ALOS for the elective pathways among participating DHBs. There was no
decrease in ALOS for the fractured NOF pathway. Collaborative improvement
methodology can be used successfully to implement orthopaedic ERAS across New
Zealand DHBs.
PMID- 28494481
TI - Enhanced hip fracture management: use of statistical methods and dataset to
evaluate a fractured neck of femur fast track pathway-pilot study.
AB - The increasing elderly population and subsequent rise in total hip fracture(s) in
this group means more effective management strategies are necessary to improve
efficiency. We have changed our patient care strategy from the emergency
department (ED), acute orthopaedic wards, operating theatre, post-operation and
rehabilitation, and called it Fracture Neck of Femur Fast Track Pathway. All
clinical data and actions were captured, integrated and displayed on a weekly
basis using 'signalfromnoise' (SFN) software. The initial four months analysis of
this project showed significant improvement in patient flow within the hospitals.
The overall length of stay was reduced by four days. Time in ED was reduced by 30
minutes, and the wait for rehabilitation reduced by three days. Overall time in
rehabilitation reduced by 3-7 days depending on facility. On average, fast track
patients spent 95 less hours in hospital, resulting in 631 bed days saved in this
period, with projected savings of NZD700,000. No adverse effects were seen in
mortality, readmission and functional improvement status. Fractured neck of femur
has increasing clinical demand in a busy tertiary hospital. Length of stay, co
morbidities and waiting time for theatres are seen as major barriers to treatment
for these conditions. Wait for rehabilitation can significantly lengthen hospital
stay; also poor communication between the individual hospital management facets
of this condition has been an ongoing issue. Lack of instant and available
electronic information on this patient group has also been seen as a major
barrier to improvement. This paper demonstrates how integration of service
components that are involved in fractured neck of femur can be achieved. It also
shows how the use of electronic data capture and analysis can give a very quick
and easily interpretable data trend that will enable change in practice. This
paper indicates that cooperation between health professionals and practitioners
can significantly improve the length of stay and the time in which patients can
be returned home. Full interdisciplinary involvement was the key to this
approach. The use of electronic data capture and analysis can be used in many
other health pathways within the health system.
PMID- 28494482
TI - Increased use of police and health-related services among those with heavy
drinkers in their lives in New Zealand.
AB - AIMS: To report population estimates of service use because of someone else's
drinking in New Zealand, investigate whether greater exposure to heavy drinkers
relates to greater service use and examine demographic predictors of such service
use. METHODS: A general population survey of respondents aged 12-80 years was
conducted in New Zealand. The sample size was 3,068 and response rate 64%.
Respondents' use of police and health-related services because of someone else's
drinking were measured along with self-reports of heavy drinkers in their lives,
demographic variables and own drinking. RESULTS: Ten percent of New Zealanders
reported having called the police at least once in the past 12 months because of
someone else's drinking-corresponding to 378,843 New Zealanders making at least
one call to police. Almost 7% of the sample, representing 257,613 New Zealanders,
reported requiring health-related services at least once for the same reason.
CONCLUSIONS: There are considerable numbers of New Zealanders requiring
intervention from police or health-related services due to the effects of someone
else's drinking. Further, increased exposure to heavy drinkers among respondents
predicted increased service use. Heavy drinkers place increased burden on police
and health-related services, not only because of directly attributable effects
but because they impact others.
PMID- 28494483
TI - The cost of major head and neck cancer surgery.
AB - AIM: This study quantified the cost of major head and neck cancer (HNC) surgery.
METHODS: Consecutive patients undergoing major HNC surgery between July 2007 and
June 2012 were identified from our head and neck database. Patient demographics,
tumour type, site, stage and types of resection and reconstruction, length of
stay and surgical complications occurring within six months of initial surgery
were retrospectively analysed. The actual cost of initial surgical treatment and
hospital income were calculated. RESULTS: Two hundred and forty-five patients
underwent major HNC surgery, most commonly for mucosal squamous cell carcinoma
(SCC) and metastatic and/or locally advanced cutaneous SCC. Neck dissection and
parotidectomy were the commonest resection procedures and free flaps the
commonest reconstructive procedures performed. Forty-two patients developed
surgical complications within six months of the initial major HNC surgery. Over
the five-year period, surgery cost a total of NZ$5,130,639.00, averaging
NZ$20,941.38 per patient, not including costs such as incidentals, while the
hospital received NZ$4,976,559.61 averaging NZ$20,229.91/patient. On average,
oral cavity cancer, metastatic and/or locally advanced skin cancer, and skull
base cancer cost NZ$22,694.72/patient, NZ$17,373.64/patient and
NZ$47,295.95/patient, respectively. CONCLUSION: Calculated hospital income
marginally covered the actual cost of major HNC surgery, which places substantial
financial burden on the hospital. The anatomic site of the tumour determines the
cost of treatment.
PMID- 28494484
TI - Is high-quality trauma care "business as usual" in New Zealand?
AB - New Zealand is on the cusp of establishing a world-class trauma system. Many of
the building blocks are in place with national and regional guidelines in both
the pre-hospital and hospital phases of care established. A dedicated clinical
workforce is available in all DHBs and national data available through the Major
Trauma Registry. The greatest threat to achieving high-quality trauma care in New
Zealand at this point is governance stability rather than clinical variability.
Now is the time to lock the trauma system into a framework not subject to
political or bureaucratic whims.
PMID- 28494485
TI - Rotorua, hydrogen sulphide and Parkinson's disease-A possible beneficial link?
AB - AIM: Rotorua city (New Zealand) is known for its 'rotten egg' smell, due to high
levels of hydrogen sulphide (H2S) concentrations emitted from local geothermal
vents. Studies have shown H2S as potentially toxic if too high in concentration.
However, some health benefits have been observed at lower concentrations. This
article summarises what is known about effects of H2S on health and postulates
whether ambient air inhalation levels of H2S in Rotorua might have a therapeutic
role in the management of motor symptoms in Parkinson's disease (PD). RESULTS:
Chronic H2S inhalation has been shown to have a protective factor on dopaminergic
neurons of animal models of PD. A large-scale survey of long-term Rotorua
residents showed no evidence of health detriment nor impairment of cognitive
functions. Intriguingly, however, participants in higher H2S exposures showed a
tendency for faster motor response times in a finger tapping test. One of the PD
Motor Rating Scale examination tests for PD is finger tapping speed, as this is
associated with motor performance. Might it be that relatively high, but safe,
H2S levels in Rotorua could help protect the degradation of dopaminergic neurons
associated with PD? CONCLUSION: An observed beneficial link between chronic H2S
inhalation in PD animal models and improved finger tapping scores in a sample of
the Rotorua population, linked to dopaminergic nerve function, is worth
investigating further.
PMID- 28494486
TI - Acute calcific tendinitis of the longus colli muscle.
PMID- 28494487
TI - A case of confirmed primary hyperaldosteronism diagnosed despite normal screening
investigations.
AB - Primary hyperaldosteronism is a common cause of hypertension in the adult
population. We report a case of histologically and biochemically confirmed
hyperaldosteronism related to an adrenal adenoma, where initial screening and
biochemical tests were potentially misleading. The case highlights the importance
of clinical suspicion in the current diagnostic approach to primary
hyperaldosteronism.
PMID- 28494488
TI - Unmet need and antenatal care.
PMID- 28494489
TI - Coeliac disease and fertility in New Zealand women.
PMID- 28494490
TI - Biomechanical Responses of Lamina Cribrosa to Intraocular Pressure Change
Assessed by Optical Coherence Tomography in Glaucoma Eyes.
AB - Purpose: The purpose of this study was to measure change in anterior lamina
cribrosa depth (ALD) globally and regionally in glaucoma eyes at different
intraocular pressures (IOP). Methods: Twenty-seven glaucoma patients were imaged
before and after IOP-lowering procedures using optical coherence tomography. The
anterior lamina was marked in approximately 25 locations in each of six radial
scans to obtain global and regional estimates of ALD. ALD and its change with IOP
were compared with optic disc damage, nerve fiber layer thickness, and visual
field loss. Results: Variables associated with deeper baseline ALD included
larger cup/disc ratio, thinner rim area, larger cup volume, thinner central
corneal thickness, and male sex (all P <= 0.02). When IOP was lowered, ALD
position became more anterior, more posterior, or was unchanged. The mean ALD
change after lowering was 27 +/- 142 MUm (P = 0.3). The mean absolute value of
ALD change was 112 +/- 90 MUm (P = 0.002). Change in ALD was greater in eyes with
lower IOP in paired comparisons (P = 0.006) but was not associated with the
magnitude of IOP lowering between imaging sessions (P = 0.94). Eyes with no
significant change in ALD tended to have more visual field loss than those with
significant anterior ALD displacement (P = 0.07). Areas within each optic nerve
head that corresponded to zones with thicker nerve fiber layer had greater ALD
positional change (P = 0.0007). Conclusions: The lamina can move either
anteriorly or posteriorly with IOP decrease, with greater displacement at lower
IOP. Glaucoma eyes and regions within glaucoma eyes associated with greater
glaucoma damage exhibited smaller responses.
PMID- 28494491
TI - Topical Delivery of Anti-VEGF Drugs to the Ocular Posterior Segment Using Cell
Penetrating Peptides.
AB - Purpose: To evaluate the efficacy of anti-VEGF agents for treating choroidal
neovascularization (CNV) when delivered topically using novel cell-penetrating
peptides (CPPs) compared with delivery by intravitreal (ivit) injection. Methods:
CPP toxicity was investigated in cell cultures. Ivit concentrations of
ranibizumab and bevacizumab after topical administration were measured using
ELISA. The biological efficacy of topical anti-VEGF + CPP complexes was compared
with ivit anti-VEGF injections using an established model of CNV. Results: CPPs
were nontoxic in vitro. In vivo, after topical eye drop delivery, CPPs were
present in the rat anterior chamber within 6 minutes. A single application of CPP
+ bevacizumab eye drop delivered clinically relevant concentrations of
bevacizumab to the posterior chamber of the rat eye in vivo. Similarly,
clinically relevant levels of CPP + ranibizumab and CPP + bevacizumab were
detected in the porcine vitreous and retina ex vivo. In an established model of
CNV, mice treated with either a single ivit injection of anti-VEGF, twice daily
CPP + anti-VEGF eye drops or daily dexamethasone gavage for 10 days all had
significantly reduced areas of CNV when compared with lasered eyes without
treatment. Conclusions: CPPs are nontoxic to ocular cells and can be used to
deliver therapeutically relevant doses of ranibizumab and bevacizumab by eye drop
to the posterior segment of mouse, rat, and pig eyes. The CPP + anti-VEGF drug
complexes were cleared from the retina within 24 hours, suggesting a daily eye
drop dosing regimen. Daily, topically delivered anti-VEGF with CPP was as
efficacious as a single ivit injection of anti-VEGF in reducing areas of CNV in
vivo.
PMID- 28494492
TI - Biomechanical Differences Between Femtosecond Lenticule Extraction (FLEx) and
Small Incision Lenticule Extraction (SmILE) Tested by 2D-Extensometry in Ex Vivo
Porcine Eyes.
AB - Purpose: To evaluate the biomechanical stability of ex vivo porcine corneas after
femtosecond lenticule extraction (FLEx) and small incision lenticule extraction
(SmILE) refractive surgeries. Methods: Forty-five porcine eyes were equally
divided into three groups: Groups 1 and 2 were treated with FLEx and SmILE
procedure, respectively. Group 3 served as control. A refractive correction of
14 diopters (D) with a 7-mm zone using either a 160-MUm flap (FLEx) or a 160-MUm
cap (SmILE) was performed. For two-dimensional (2D) elastic and viscoelastic
biomechanical characterization, two testing cycles (preconditioning stress-strain
curve from 1.27 to 12.5 N, stress-relaxation at 12.5 N during 120 seconds) were
conducted. Young's modulus and Prony constants were calculated. Results: At 0.8%
of strain, FLEx (370 +/- 36 kPa) could resist a significantly lower stress than
SmILE (392 +/- 19 kPa, P = 0.046) and the control group (402 +/- 30 kPa, P =
0.013). Also, FLEx (46.1 +/- 4.5 MPa) had a significantly lower Young's modulus
than the control group (50.2 +/- 3.4 MPa, P = 0.008). The Young's modulus of
SmILE (48.6 +/- 2.5 MPa) had values situated between untreated corneas and FLEx
treated corneas. When compared to untreated controls, the stress resistance
decreased by 8.0% with FLEx and 2.5% with SmILE; Young's modulus decreased by
5.1% with FLEx and 1.04% with SmILE. With a cap-based procedure, both anterior
cap and stromal bed carry the intraocular pressure, while in a flap-based
procedure, only the stromal bed does. Conclusions: Compared to flap-based
procedures like FLEx, the cap-based technique SmILE can be considered superior in
terms of biomechanical stability, when measured experimentally in ex vivo porcine
corneas.
PMID- 28494493
TI - Flexible Optical Waveguides for Uniform Periscleral Cross-Linking.
AB - Purpose: Scleral cross-linking (SXL) with a photosensitizer and light is a
potential strategy to mechanically reinforce the sclera and prevent progressive
axial elongation responsible for severe myopia. Current approaches for light
delivery to the sclera are cumbersome, do not provide uniform illumination, and
only treat a limited area of sclera. To overcome these challenges, we developed
flexible optical waveguides optimized for efficient, homogeneous light delivery.
Methods: Waveguides were fabricated from polydimethylsiloxane elastomer. Blue
light (445 nm) is coupled into the waveguide with an input fiber. Light delivery
efficiency from the waveguide to scleral tissue was measured and fit to a
theoretical model. SXL was performed on fresh porcine eyes stained with 0.5%
riboflavin, using irradiances of 0, 25, and 50 mW/cm2 around the entire equator
of the eye. Stiffness of scleral strips was characterized with tensiometry.
Results: Light delivery with a waveguide of tapered thickness (1.4-0.5 mm)
enhanced the uniformity of light delivery, compared to a flat waveguide,
achieving a coefficient of variation of less than 10%. At 8% strain, sclera cross
linked with the waveguides at 50 mW/cm2 for 30 minutes had a Young's modulus of
10.7 +/- 1.0 MPa, compared to 5.9 +/- 0.5 MPa for no irradiation, with no
difference in stiffness between proximally and distally treated halves. The
stiffness of waveguide-irradiated samples did not differ from direct irradiation
at the same irradiance. Conclusions: We developed flexible waveguides for
periscleral cross-linking. We demonstrated efficient and uniform stiffening of a
5-mm-wide equatorial band of scleral tissue.
PMID- 28494494
TI - Multifocal ERG Responses in Subjects With a History of Preterm Birth.
AB - Purpose: The purpose of this study is to assess cone-mediated central retinal
function in children with a history of preterm birth, including subjects with and
without retinopathy of prematurity (ROP). The multifocal electroretinogram
(mfERG) records activity of the postreceptor retinal circuitry. Methods: mfERG
responses were recorded to an array of 103 hexagonal elements that subtended 43
degrees around a central fixation target. The amplitude and latency of the first
negative (N1) and first positive (P1) response were evaluated in six concentric
rings centered on the fovea. Responses were recorded from 40 subjects with a
history of preterm birth (severe ROP, mild ROP, no ROP) and 19 term-born control
subjects. Results: The amplitude of N1 and P1 varied significantly with
eccentricity and ROP severity. For all four groups, these amplitudes were largest
in the center and decreased with eccentricity. At all eccentricities, N1
amplitude was significantly smaller in severe ROP and did not differ
significantly among the other three groups (mild ROP, no ROP, term-born
controls). P1 amplitude in all preterm groups was significantly smaller than in
controls; P1 amplitude was similar in no ROP and mild ROP and significantly
smaller in severe ROP. Conclusions: These results provide evidence that premature
birth alone affects cone-mediated central retinal function and that the magnitude
of the effect varies with severity of the antecedent ROP. The lack of difference
in mfERG amplitude between the mild and no ROP groups is evidence that the effect
of ROP on the neurosensory retina may not depend solely on appearance of abnormal
retinal vasculature.
PMID- 28494495
TI - Mutations in LRP5,FZD4, TSPAN12, NDP, ZNF408, or KIF11 Genes Account for 38.7% of
Chinese Patients With Familial Exudative Vitreoretinopathy.
AB - Purpose: Familial exudative vitreoretinopathy (FEVR) is a severe hereditary
retinal disorder characterized by defects in retinal vascular development. To
date, six genes have been reported to be responsible for this disease, including
LRP5, FZD4, TSPAN12, NDP, ZNF408, and KIF11. The purpose of our study was to
investigate the genetic defects in Chinese patients with FEVR through mutational
analyses of 31 pedigrees. Methods: Clinical data and peripheral blood were
collected from 31 pedigrees with FEVR. All coding sequences and intron/exon
junctions were amplified and sequenced comprehensively, followed by cosegregation
testing to verify suspected variants in the family members. Finally, we assessed
clinical relevance of the identified mutations, according to the standards and
guidelines from the American College of Medical Genetics and Genomics. Results:
Twelve index cases (12/31, 38.7%) were confirmed to harbor mutations in the known
genes, including one previously reported mutation and 11 novel mutations. Among
the detected mutations, LRP5 accounted for the largest proportion with a mean
mutation rate of 16.1% (5/31, 16.1%), followed by NDP (3/31, 9.7%), FZD4 (2/31,
6.5%), TSPAN12 (1/31, 3.2%), and KIF11 (1/31, 3.2%). All the novel changes were
predicted to be pathogenic by a series of bioinformatics analyses. Conclusions:
We comprehensively screened six known disease-causing genes in 31 pedigrees with
FEVR and achieved a clear picture of the mutation spectrum in Chinese patients
with FEVR, which highlights the importance and utility of clinical genetic
diagnosis.
PMID- 28494496
TI - Sensitivity to Binocular Disparity is Reduced by Mild Traumatic Brain Injury.
AB - Purpose: The impairment of visual functions is one of the most common complaints
following mild traumatic brain injury (mTBI). Traumatic brain injury-associated
visual deficits include blurred vision, reading problems, and eye strain. In
addition, previous studies have found evidence that TBI can diminish early
cortical visual processing, particularly for second-order stimuli. We
investigated whether cortical processing of binocular disparity is also affected
by mTBI. Methods: In order to investigate the influence of mTBI on global
stereopsis, we measured the quick Disparity Sensitivity Function (qDSF) in 22
patients with mTBI. Patients with manifest strabismus and double vision were
excluded. Compared with standard clinical tests, the qDSF is unique in that it
offers a quick and accurate estimate of thresholds across the whole spatial
frequency range. Results: Results show that disparity sensitivity in the mTBI
patients were significantly reduced compared with the normative dataset (n = 61).
The peak spatial frequency was not affected. Conclusions: Our results suggest
that the reduced disparity sensitivity in patients with mTBI is more likely
caused by cortical changes (e.g., axonal shearing, or reduced interhemispheric
communication) rather than oculomotor dysfunction.
PMID- 28494497
TI - Effect of Anatomical and Developmental Factors on the Risk of Unplanned
Extubation in Critically Ill Newborns.
PMID- 28494498
TI - Antenatal Exposure to Magnesium Sulfate and Spontaneous Intestinal Perforation
and Necrotizing Enterocolitis in Extremely Preterm Neonates.
PMID- 28494499
TI - ?
AB - The present study aimed to evaluate the diagnostic value of echocardiography in
measuring the thickness of epicardial adipose tissue (EAT) of the patients of
type 2 diabetes mellitus (T2DM) and its correlation with the intimal-medial
thickness of the carotid artery (cIMT) to investigate the relationship between
EAT and cIMT. 68 patients of T2DM were enrolled and were divided into 2 groups:
group of T2DM with duration<=10 years (35 cases) and group of T2DM with
duration>10 years (33 cases). And 30 healthy subjects were enrolled as the
control group. The thickness of EAT and cIMT were measured by echocardiography
and high-frequency ultrasonography. The thickness of EAT and IMT of the carotid
artery of 2 type 2 diabetic groups (duration<=10 years and>10 years) were
significantly higher than that of the control group (all p<0.05), and the
thickness of EAT and cIMT of the group of T2DM with duration>10 years were
significantly higher than that of the group of T2DM with duration<=10 years
(p<0.05). In univariate analysis, the thickness of EAT was positively and
significantly associated with age (r=0.412, p<0.05), BMI (r=0.566, p<0.05), waist
circumference (r=0.475, p<0.05), LDL (r=0.425, p<0.05), TG (r=0.496, p<0.05),
duration of diabetes (r=0.384, p<0.05) and cIMT (r=0.456, p<0.05). In multiple
stepwise regression analyses, age, BMI and IMT of carotid artery were appeared to
be significantly associated with EAT (p<0.05 for all). In conclusion, routine
screening of EAT and cIMT by ultrasonography in type 2 diabetic patients helps us
to predict cardiovascular risks and prevent further development of cardiovascular
complications.
PMID- 28494500
TI - ?
AB - Metabolic syndrome (MetS) consist in a combination of cardiovascular risk factors
including elevated blood pressure, dyslipidemia, insulin resistance,
hyperglycemia and abdominal obesity. Exercise performed before, during and after
pregnancy can exert positive effects to counteract MetS risk factors. Here this
review aims to analyze the effects of exercise performed before (fathers and
mothers) and after periconception (mothers) by using experimental models and its
effects on MetS risk factors in offspring. All selected studies investigated the
effects of aerobic exercise before, during and after periconception on MetS risk
factors in offspring, while no studies utilizing resistance exercise were found.
Exercise performed before, and after periconception exerted preventive effects in
the offspring, with regards to MetS risk factors. However, more studies focusing
on the dose-response of exercise before, and after periconception may reveal
interesting results on MetS risk factor in offspring. Thus, the prevention from
chronic degenerative diseases can be improved by mother exercise and might be
associated with epigenetic mechanisms, such as DNA methylation, hPTMs (histone
post translational modifications), non-coding RNAs (ex: MicroRNAs) which results
phenotypic modifications by individual genome reprograming. Otherwise, results
from paternal exercise are inconclusive at this time.
PMID- 28494501
TI - European Pediatric Surgical Training.
PMID- 28494502
TI - Role of New Media for the Young Pediatric Surgeon: Fighting Exponential Knowledge
Growth with Moore's Law.
PMID- 28494503
TI - Leadership in Pediatric Surgery from a Trainee's Perspective.
PMID- 28494504
TI - Metabolic Syndrome and Aggressive Prostate Cancer at Initial Diagnosis.
AB - Links between metabolic syndrome and prostate cancer after androgen deprivation
therapy are emerging. The aim of the research was to investigate the association
of metabolic syndrome and aggressive prostate malignancy, at initial diagnosis,
without the influence of hormonal treatment. Retrospective analysis of 133
patients with prostate tumor diagnosis between 2007 and 2009 was conducted.
Patients with prostate cancer were subdivided in 2 groups according to Gleason
score: Gleason score>=7 as high-grade prostate tumor (Group 1) and <7 (Group 2)
as low-grade prostate tumor. Metabolic syndrome was defined according to
International Diabetes Federation and the American Heart Association/National
Heart, Lung, and Blood Institute definition. Metabolic syndrome was significantly
associated with aggressive prostate cancer (OR 1.87, p<0.05) and a reduced risk
of low-grade prostate cancer (OR 0.53, p<0.05) at initial diagnosis, without the
influence of endocrine therapy. In our study, patients with metabolic syndrome
were more likely to present with more aggressive prostate carcinoma vs. patients
without metabolic syndrome. Further research should elucidate these relations in
larger samples to confirm these associations and to stabilize future prevention
and therapeutic strategies.
PMID- 28494505
TI - Genome-wide analysis of somatic copy number alterations and chromosomal breakages
in osteosarcoma.
AB - Osteosarcoma (OS) is the most common primary malignant bone tumor in children and
adolescents. It is characterized by highly complex karyotypes with structural and
numerical chromosomal alterations. The observed OS-specific characteristics in
localization and frequencies of chromosomal breakages strongly implicate a
specific set of responsible driver genes or a specific mechanism of fragility
induction. In this study, a comprehensive assessment of somatic copy number
alterations (SCNAs) was performed in 160 OS samples using whole-genome CytoScan
High Density arrays (Affymetrix, Santa Clara, CA). Genes or regions frequently
targeted by SCNAs were identified. Breakage analysis revealed OS specific
unstable regions in which well-known OS tumor suppressor genes, including TP53,
RB1, WWOX, DLG2 and LSAMP are located. Certain genomic features, such as
transposable elements and non-B DNA-forming motifs were found to be significantly
enriched in the vicinity of chromosomal breakage sites. A complex breakage
pattern-chromothripsis-has been suggested as a widespread phenomenon in OS. It
was further demonstrated that hyperploidy and in particular chromothripsis were
strongly correlated with OS patient clinical outcome. The revealed OS-specific
fragility pattern provides novel clues for understanding the biology of OS.
PMID- 28494507
TI - Subepidermal moisture detection of pressure induced tissue damage on the trunk:
The pressure ulcer detection study outcomes.
AB - We examined the relationship between subepidermal moisture measured using surface
electrical capacitance and visual skin assessment of pressure ulcers at the trunk
location (sacral, ischial tuberosities) in 417 nursing home residents residing in
19 facilities. Participants were on average older (mean age of 77 years), 58%
were female, over half were ethnic minorities (29% African American, 12% Asian
American, and 21% Hispanic), and at risk for pressure ulcers (mean score for
Braden Scale for Predicting Pressure Ulcer Risk of 15.6). Concurrent visual
assessments and subepidermal moisture were obtained at the sacrum and right and
left ischium weekly for 16 weeks. Visual assessment was categorized as normal,
erythema, stage 1 pressure ulcer, Deep Tissue Injury or stage 2+ pressure ulcer
using the National Pressure Ulcer Advisory Panel 2009 classification system.
Incidence of any skin damage was 52%. Subepidermal moisture was measured with a
dermal phase meter where higher readings indicate greater moisture (range: 0-70
tissue dielectric constant), with values increasing significantly with the
presence of skin damage. Elevated subepidermal moisture values co-occurred with
concurrent skin damage in generalized multinomial logistic models (to control for
repeated observations) at the sacrum, adjusting for age and risk. Higher
subepidermal moisture values were associated with visual damage 1 week later
using similar models. Threshold values for subepidermal moisture were compared to
visual ratings to predict skin damage 1 week later. Subepidermal moisture of 39
tissue dielectric constant units predicted 41% of future skin damage while visual
ratings predicted 27%. Thus, this method of detecting early skin damage holds
promise for clinicians, especially as it is objective and equally valid for all
groups of patients.
PMID- 28494508
TI - Look into my eyes: An unusual first presentation of sickle cell disease.
PMID- 28494506
TI - Minimal residual disease eradication with epigenetic therapy in core binding
factor acute myeloid leukemia.
AB - Recurrent translocations, t(8;21) or inv(16), in core binding factor acute
myeloid leukemia (CBF-AML) are amenable to monitoring for minimal residual
disease (MRD) with reverse transcriptase polymerase chain reaction (RTPCR).
Despite a favorable prognosis, disease relapse remains the single cause of
treatment failure in CBF-AML. Fusion products of these translocations recruit
epigenetic silencing complexes resulting in hematopoietic maturation arrest. We
hypothesized that maintenance therapy with hypomethylating agents (HMA),
including decitabine (DAC) and azacitidine (AZA) after induction/consolidation,
can be used for MRD elimination to ultimately prolong relapse free survival. Real
time quantitative (RTPCR) trends were reviewed in 23 patients (median age 53
years) with CBF-AML that received HMA therapy following induction/consolidation
with fludarabine, cytarabine, and G-CSF (FLAG) with low dose gemtuzumab or
idarubicin (NCT00801489). Of the 23 patients evaluated, 17 had a detectable RTPCR
at HMA initiation. Five patients had progressive disease and a notable increase
in RTPCR values over 1-2 cycles of HMA therapy. Twelve patients did not fail HMA
and had a median RTPCR at HMA initiation of 0.06 (range, 0.01-0.91). Unlike the
HMA failure subset, 11 of these patients had a reduction in RTPCR after the first
or second cycle of HMA. Our data suggests that CBF-AML patients with low levels
of RTPCR (between 0.01 and 0.05) at the conclusion of induction/consolidation
chemotherapy benefit most from maintenance HMA, particularly those that have a
reduction in the RTPCR within the first two cycles of HMA therapy.
PMID- 28494509
TI - Estimates of total body iron indicate 19 mg and 38 mg oral iron are equivalent
for the mitigation of iron deficiency in individuals experiencing repeated
phlebotomy.
AB - Iron deficiency anemia is a common clinical condition often treated with tablets
containing 65 mg of elemental iron. Such doses can elicit gastrointestinal side
effects lowering patient compliance. Oral iron supplements also increase hepcidin
production causing decreased fractional absorption of subsequent doses. Frequent
blood donors often become iron deficient. Therefore, they were enrolled in a two
year study involving continued blood donations and randomization to receive no
pill, placebo, 19, or 38 mg ferrous gluconate for 60 days. Total body iron (TBI)
did not change for the subset of donors in the no pill and placebo groups who
completed both enrollment and final visits (P = .21 and P = .28, respectively).
However, repeated measures regression analysis on the complete dataset estimated
a significant decrease in TBI of 52 mg/year for the placebo and no pill groups (P
= .001). The effects of 19 and 38 mg iron supplementation on TBI were
indistinguishable (P = .54). TBI increased by 229 mg after the initial 60 days of
iron supplementation (P < .0001) and was maintained at this higher level with
continued iron supplementation following each subsequent donation. The TBI
increase was apportioned 51 mg to red cell iron (P < .0001) and 174 mg to storage
iron (P < .0001). Changes in storage iron were negatively impacted by 57 mg due
to concurrent antacid use (P = .04). These findings in blood donors suggest that
much lower doses of iron than are currently used will be effective for clinical
treatment of iron deficiency anemia.
PMID- 28494510
TI - Response to 'Colorectal cancer resection in the Australian nonagenarian patient'.
PMID- 28494511
TI - The ethnic distribution of sessile serrated polyps in the United States is
inversely associated with Helicobacter pylori prevalence.
AB - AIM: Little is known about the epidemiology of sessile serrated polyps (SSP). Our
study aimed to investigate the influence of Helicobacter pylori gastritis and
patient demographic characteristics (age, gender, ethnicity) on the prevalence of
SSP using a large national database of patients undergoing bi-directional
endoscopy. METHOD: De-identified patient data were extracted from the Miraca Life
Sciences electronic database of histopathological reports. Using multivariate
logistic regression analysis, the influence of H. pylori gastritis and
demographic characteristics on the occurrence of SSP were expressed as odds
ratios (OR) with their 95% confidence intervals (CI). RESULTS: The total study
population comprised 228 506 subjects, of whom 28 890 carried a diagnosis of H.
pylori gastritis and 11 285 SSP. Age (OR 4.35, 95% CI: 3.82-4.96), female gender
(0.92, 0.88-0.95) and H. pylori gastritis (0.94, 0.88-0.99) exerted the strongest
influence on the occurrence of SSP. In comparison with the population comprising
Caucasians and African Americans, SSP were less common among subjects of Hispanic
(0.67, 0.62-0.73), East Asian (0.59, 0.50-0.69), Indian (0.43, 0.27-0.64) or
Middle Eastern descent (0.61, 0.41-0.87). All these ethnic subgroups were also
characterized by a higher prevalence of H. pylori than the comparison group. A
low prevalence of H. pylori was significantly associated with a high prevalence
of SSP (R2 = 0.82, P < 0.001). CONCLUSION: The prevalence of SSP within the
United States is characterized by a marked ethnic variation. The inverse
correlation between the prevalence of H. pylori and SSP suggests that gastric
infection with H. pylori may be partly responsible for the observed ethnic
distribution of SSP.
PMID- 28494512
TI - Gene expression profiling of skeletal muscle after volumetric muscle loss.
AB - Volumetric muscle loss (VML), usually occurring following traumatic injury,
results in a composite loss of muscle mass. These injuries manifest as decreased
strength and functional impairments. Clinically, these injuries often heal with
fibrosis, as opposed to skeletal muscle regeneration. This study examines the
healing patterns of a skeletal muscle following VML in a murine model. Eight-week
old male C57BL/6J mice used in the study underwent either bilateral VML injury or
cryoinjury, a widely used model known to induce skeletal muscle regeneration.
Skeletal muscle was harvested at 2 and 4 weeks following injury and subjected to
histological analysis. H&E staining demonstrated skeletal muscle regeneration
following cryoinjury, but not VML, at either timepoint post-injury. Additionally,
samples were analyzed using a wound-healing PCR array to identify differentially
regulated genes of interest in VML and cryoinjury, as compared to noninjured
controls. The gene array data further demonstrated prolonged inflammation and
increased pro-fibrotic activity in the VML injured muscles, as compared to
cryoinjury. In addition, IGF1, a known myogenic factor, was significantly
decreased following VML, as compared to cryoinjury, in both ELISA and PCR. This
study offers an insight into the pathophysiology of VML injury and reveals a gene
profile of a nonregenerating skeletal muscle.
PMID- 28494513
TI - Patients with 'interval' colorectal cancers have worse outcomes compared with
cancers in patients who decline the National Bowel Cancer Screening Programme -
Results from a Multicentre Study.
PMID- 28494514
TI - Urinary prednisolone excretion is a determinant of serum hepcidin levels in renal
transplant recipients.
PMID- 28494515
TI - Potent and selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1
labeled with carbon-13 and carbon-14.
AB - (S)-6-(2-Hydroxy-2-methylpropyl)-3-((S)-1-(4-(1-methyl-2-oxo-1,2-dihydropyridin-4
yl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one (1) and (4aR,9aS)-1-(1H
benzo[d]midazole-5-carbonyl)-2,3,4,4a,9,9a-hexahydro-1-H-indeno[2,1-b]pyridine-6
carbonitrile hydrochloride (2) are potent and selective inhibitor of 11beta
hydroxysteroid dehydrogenase type 1 enzyme. These 2 drug candidates developed for
the treatment of type-2 diabetes were prepared labeled with carbon-13 and carbon
14 to enable drug metabolism, pharmacokinetics, bioanalytical, and other studies.
In the carbon-13 synthesis, benzoic-13 C6 acid was converted in 7 steps and in
16% overall yield to [13 C6 ]-(1). Aniline-13 C6 was converted in 7 steps to 1H
benzimidazole-1-2,3,4,5,6-13 C6 -5-carboxylic acid and then coupled to a
tricyclic chiral indenopiperidine to afford [13 C6 ]-(2) in 19% overall yield.
The carbon-14 labeled (1) was prepared efficiently in 2 radioactive steps in 41%
overall yield from an advanced intermediate using carbon-14 labeled methyl
magnesium iodide and Suzuki-Miyaura cross coupling via in situ boronate
formation. As for the synthesis of [14 C]-(2), 1H-benzimidazole-5-carboxylic-14 C
acid was first prepared in 4 steps using potassium cyanide-14 C, then coupled to
the chiral indenopiperidine using amide bond formation conditions in 26% overall
yield.
PMID- 28494516
TI - The Modulation of the Startle Reflex as Predictor of Alcohol Use Disorders in a
Sample of Heavy Drinkers: A 4-Year Follow-Up Study.
AB - BACKGROUND: Previous studies demonstrated that patients with alcohol use
disorders (AUDs) show altered startle reflex responses to alcohol-related
stimuli. However, there is little information about the role of these altered
responses in the development of AUDs. This study examined the startle reflex
response to different visual stimuli and the role of these patterns in the
development of AUDs in a 4-year follow-up. METHODS: Two hundred and thirty-nine
(nondependent) heavy-drinking participants were selected. In the baseline period,
the startle reflex responses to alcohol-related, aversive, appetitive, and
neutral pictures were assessed. Startle reflex responses to these pictures were
used as predictive variables. Status drinking (alcohol dependence and
nondependence) assessed at 4-year follow-up was used as outcome measure. RESULTS:
At the 4-year follow-up assessment, 46% of participants fulfilled DSM-IV alcohol
abuse or dependence criteria. Alcohol dependence status was predicted by an
attenuated startle reflex response to alcohol-related and aversive pictures.
CONCLUSIONS: This study revealed that an attenuated modulation of startle reflex
response to alcohol-related and aversive stimuli could be used as a clinical
marker to predict the development of AUDs in participants with previous alcohol
consumption.
PMID- 28494517
TI - Exploration of peripapillary vessel density in highly myopic eyes with
peripapillary intrachoroidal cavitation and its relationship with ocular
parameters using optical coherence tomography angiography.
AB - IMPORTANCE: Identifying changes of peripapillary vessel density in highly myopic
eyes with peripapillary intrachoroidal cavitation by optical coherence tomography
angiography. BACKGROUND: To investigate peripapillary vessel density and its
relationship with other ocular parameters in highly myopic eyes with
peripapillary intrachoroidal cavitation. DESIGN: Hospital-based, cross-sectional
study. PARTICIPANTS: Thirty-five highly myopic eyes with peripapillary
intrachoroidal cavitation, 46 highly myopic eyes without peripapillary
intrachoroidal cavitation and 36 normal eyes were included in this study.
METHODS: All participants underwent optical coherence tomography angiography to
image the retinal vasculature in the peripapillary areas, including the radial
peripapillary capillaries and optic nerve head layer. Correlations between vessel
density and ocular metrics were analysed. MAIN OUTCOME MEASURES: Peripapillary
vessel density. RESULTS: In highly myopic eyes, vessel density was significantly
lower in eyes with peripapillary intrachoroidal cavitation than in those without
in peripapillary (P = 0.014, P = 0.037), inferotemporal (P < 0.001, P < 0.001)
and superotemporal (P = 0.014, P = 0.009) areas. In the radial peripapillary
capillaries layer, vessel density was negatively correlated with peripapillary
atrophy area (P = 0.012) and myopic maculopathy (P = 0.002), and in the optic
nerve head layer, it was negatively associated with a diagnosis of peripapillary
intrachoroidal cavitation (P = 0.012) and myopic maculopathy (P < 0.001). In
addition, it was positively correlated with retinal nerve fibre layer thickness
in both layers (P < 0.001). CONCLUSIONS AND RELEVANCE: Highly myopic eyes with
peripapillary intrachoroidal cavitation had lower peripapillary vessel densities,
especially in the temporal area, than those without.
PMID- 28494518
TI - Correlates of resistance and relapse during blinatumomab therapy for
relapsed/refractory acute lymphoblastic leukemia.
AB - We retrospectively analyzed 65 patients with refractory/relapsed (r/r) ALL who
were treated with blinatumomab for predictors of leukemia response as well as
clinical patterns of relapse and resistance with particular focus on
downregulation of CD19 expression and extramedullary disease (EM-ALL). The
complete remission (CR) rate was 51%, and 15 (45%) responders underwent
allogeneic hematopoietic cell transplantation (HCT) in CR. High leukemia burden
(bone marrow blasts >50%) (P = .02), history of prior EM-ALL (P = .005), and
active EM-ALL at the time of initiating blinatumomab (P = .05) predicted lower CR
rate. Among refractory cases, 13 (41%) had evidence of EM-ALL progression, and
CD19 expression was negative or dim in 18% and 23%, respectively. Among
responders, 20 (61%) subsequently relapsed among whom EM-ALL relapse occurred in
8 (40%) patients, and CD19 expression was negative or dim in 35 and 6% of
evaluable cases, respectively. Pretreatment moderate/strong CD19 expression (P =
.01) and history of prior EM-ALL during ALL course (P = .04) were risk factors
for developing EM-ALL at progression/relapse. However, no pretreatment factors
predicted progression/relapse with CD19-negative ALL. Overall-survival (OS) and
even-free survival were improved for patients underwent allogeneic HCT compared
to responders who did not. Furthermore, OS was superior for patients responded to
blinatumomab compared to those who did not. Extramedullary and CD19-negative
disease are common during blinatumomab failure in r/r ALL. In addition to high
leukemia burden, concurrent or prior history EM-ALL were associated with lower
response to blinatumomab. Higher CD19 expression as well as prior history of EM
ALL were associated with EM-ALL at the time of blinatumomab failure.
PMID- 28494519
TI - Molecular insights into Cassava brown streak virus susceptibility and resistance
by profiling of the early host response.
AB - Cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV)
are responsible for significant cassava yield losses in eastern sub-Saharan
Africa. To study the possible mechanisms of plant resistance to CBSVs, we
inoculated CBSV-susceptible and CBSV-resistant cassava varieties with a mixed
infection of CBSVs using top-cleft grafting. Transcriptome profiling of the two
cassava varieties was performed at the earliest time point of full infection (28
days after grafting) in the susceptible scions. The expression of genes encoding
proteins in RNA silencing, salicylic acid pathways and callose deposition was
altered in the susceptible cassava variety, but transcriptional changes were
limited in the resistant variety. In total, the expression of 585 genes was
altered in the resistant variety and 1292 in the susceptible variety.
Transcriptional changes led to the activation of beta-1,3-glucanase enzymatic
activity and a reduction in callose deposition in the susceptible cassava
variety. Time course analysis also showed that CBSV replication in susceptible
cassava induced a strong up-regulation of RDR1, a gene previously reported to be
a susceptibility factor in other potyvirus-host pathosystems. The differences in
the transcriptional responses to CBSV infection indicated that susceptibility
involves the restriction of callose deposition at plasmodesmata. Aniline blue
staining of callose deposits also indicated that the resistant variety displays a
moderate, but significant, increase in callose deposition at the plasmodesmata.
Transcriptome data suggested that resistance does not involve typical antiviral
defence responses (i.e. RNA silencing and salicylic acid). A meta-analysis of the
current RNA-sequencing (RNA-seq) dataset and selected potyvirus-host and virus
cassava RNA-seq datasets revealed that the conservation of the host response
across pathosystems is restricted to genes involved in developmental processes.
PMID- 28494520
TI - Characterization of TP53 mutations in clonal cytopenia of undetermined
significance.
PMID- 28494521
TI - Topical 1% propranolol cream promotes cutaneous wound healing in spontaneously
diabetic mice.
AB - : Diabetic foot ulcers (DFUs) are a constant threat to diabetic patients and can
lead to amputations and even death. Intralesional administration of propranolol
in diabetic wounds has not been reported previously. This study aimed to
investigate the efficacy of propranolol cream in diabetic wounds. Fifty-six
spontaneously diabetic mice were divided into the propranolol group and the
control group. After preparing full-thickness wounds on the back of the mice, 1%
propranolol cream was topically applied to wounds in the experimental group and
0% propranolol cream in controls. The wound sizes were measured and calculated
against the original area. The wounds were analyzed up to 21 days after injury.
At all evaluation time-points, the wound size (%) in the propranolol group was
significantly smaller than in the controls. Epidermal growth factor (EGF) protein
expression increased in the experimental vs. CONTROL GROUP: Vascular endothelial
growth factor (VEGF) expression was significantly lower in the experimental vs.
control group whereas NG2 proteoglycan was increased throughout the study.
However, matrix metallopeptidase (MMP)-9 expression was at first significantly
higher in the experimental vs. control group then the MMP-9 protein level in the
control group increased and surpassed that in the experimental group. In
conclusion, intralesional administration of 1% propranolol cream promotes
reepithelialization and regulates abnormal angiogenesis in diabetic wounds.
Propranolol cream may become a new drug for the treatment of DFUs.
PMID- 28494522
TI - Response to Bethune et al.
PMID- 28494523
TI - Korean Thyroid Imaging Reporting and Data System features of follicular thyroid
adenoma and carcinoma: a single-center study.
AB - PURPOSE: This study aimed to assess the diagnostic efficacy of Korean Thyroid
Imaging Reporting and Data System (K-TIRADS) features for distinguishing
follicular thyroid adenoma (FTA) from follicular thyroid carcinoma (FTC).
METHODS: From January 2013 to July 2016, 46 follicular neoplasms in 45 patients
who underwent preoperative thyroid ultrasonography (US) and thyroid surgery were
included. The US features of each thyroid nodule were retrospectively evaluated
by a single radiologist using a picture archiving and communication system. The
diagnostic indices of K-TIRADS for follicular neoplasms were calculated according
to whether K-TIRADS category 4 lesions were excluded or classified as benign or
malignant. RESULTS: Of the 46 follicular neoplasms (mean size, 3.1+/-1.6 cm), 37
were FTAs (mean size, 3.1+/-1.7 cm) and nine were FTCs (mean size, 3.0+/-1.5 cm).
A statistically significant difference was found between FTAs and FTCs regarding
the margin (P=0.035), while no significant differences were observed in the
composition, echogenicity, shape, orientation, calcification, or vascularity of
the lesions (P<0.05). The FTAs belonged to K-TIRADS categories 3 (n=22) and 4
(n=15), while the FTCs belonged to K-TIRADS categories 3 (n=4), 4 (n=4), and 5
(n=1). However, there was no statistically significant difference in the
distribution of K-TIRADS categories between FTAs and FTCs (P=0.184). CONCLUSION:
K-TIRADS features were not helpful for distinguishing FTA from FTC, although
follicular neoplasms showed a high prevalence of K-TIRADS categories 3 and 4.
PMID- 28494524
TI - Ultrasonographic findings of posterior interosseous nerve syndrome.
AB - PURPOSE: The purpose of this study was to evaluate the ultrasonographic findings
associated with posterior interosseous nerve (PIN) syndrome. METHODS: Approval
from the Institutional Review Board was obtained. A retrospective review of 908
patients' sonographic images of the upper extremity from January 2001 to October
2010 revealed 10 patients suspicious for a PIN abnormality (7 male and 3 female
patients; mean age of 51.8+/-13.1 years; age range, 32 to 79 years). The
ultrasonographic findings of PIN syndrome, including changes in the PIN and
adjacent secondary changes, were evaluated. The anteroposterior diameter of the
pathologic PIN was measured in eight patients and the anteroposterior diameter of
the contralateral asymptomatic PIN was measured in six patients, all at the level
immediately proximal to the proximal supinator border. The size of the pathologic
nerves and contralateral asymptomatic nerves was compared using the Mann-Whitney
U test. RESULTS: Swelling of the PIN proximal to the supinator canal by
compression at the arcade of Frohse was observed in four cases. Swelling of the
PIN distal to the supinator canal was observed in one case. Loss of the
perineural fat plane in the supinator canal was observed in one case. Four soft
tissue masses were noted. Secondary denervation atrophy of the supinator and
extensor muscles was observed in two cases. The mean anteroposterior diameter of
the pathologic nerves (n=8, 1.79+/-0.43 mm) was significantly larger than that of
the contralateral asymptomatic nerves (n=6, 1.02+/-0.22 mm) (P=0.003).
CONCLUSION: Ultrasonography provides high-resolution images of the PIN and helps
to diagnose PIN syndrome through visualization of its various causes and adjacent
secondary changes.
PMID- 28494526
TI - Ultrasonographic evaluation of women with pathologic nipple discharge.
AB - Nipple discharge is a common symptom that is alarming for the patient since it
can be a presenting symptom of breast cancer. Breast imaging is used to examine
women with pathologic nipple discharge in order to detect any lesions that may be
present and to assist in the differential diagnosis. The modalities of breast
imaging include mammography, breast ultrasonography (US), and magnetic resonance
imaging. Breast US is currently considered to be useful for the visualization of
ductal structures and intraductal lesions that cause nipple discharge. In this
review, we discuss US techniques that assist in the clear visualization of ductal
structures and intraductal lesions in patients with nipple discharge. Controversy
remains regarding the evaluation and management of patients with nipple
discharge, and we summarize the results available in the currently published
literature.
PMID- 28494525
TI - Ultrasonography of pediatric urogenital emergencies: review of classic and new
techniques.
AB - Urogenital emergencies are fairly common in the pediatric population, and a
timely and correct diagnosis is necessary to avoid possible future infertility.
In this field, ultrasonography is essential, as it has the advantages of being
radiation-free and readily accessible. In particular, a high-frequency transducer
allows precise evaluation of the morphology and vascularity of the scrotum, which
is on the surface of the body. Beyond conventional techniques, new advanced
imaging techniques have been developed, including elastography and contrast
enhanced ultrasonography. However, several pitfalls remain in the diagnosis of
urogenital diseases using ultrasonography. Thus, accurate knowledge and
sufficient experience with the technique are essential for making a correct
diagnosis. This review provides an overview of pediatric urogenital emergency
pathologies and recent ultrasonography techniques.
PMID- 28494527
TI - Relationships Among Factors Relevant to Abdominal Fat and Age-Related Hearing
Loss.
AB - OBJECTIVES: Metabolic syndrome is related with abdominal fat and with age-related
hearing loss (ARHL). In this study, we evaluated the association between a
variety of factors relevant to abdominal fat (FRAs) and hearing thresholds.
METHODS: We reviewed retrospectively the medical records of 2,602 subjects aged
over 40 years with symmetrical sensorineural hearing loss who underwent abdominal
fat computed tomography (CT) scans. Univariate and multivariate linear regression
analyses were used to demonstrate the association between each FRA and hearing
thresholds at low and high frequencies. RESULTS: Four of 5 FRAs were associated
with hearing thresholds at high frequencies in males. All FRAs examined showed a
relationship with hearing thresholds at low frequencies in females. Diabetes
mellitus (DM) among clinical factors and visceral adipose tissue (VAT) among the
5 FRAs were the most reflective of hearing thresholds in both males and females.
CONCLUSION: We found that FRAs were associated with hearing loss with frequency
specific characteristics according to sex and reinforced that DM and VAT is
particularly an important role for hearing.
PMID- 28494528
TI - A comparative study of sorafenib and metronomic chemotherapy for Barcelona Clinic
Liver Cancer-stage C hepatocellular carcinoma with poor liver function.
AB - BACKGROUND/AIMS: Metronomic chemotherapy (MET) is frequently administered in
comparatively low doses as a continuous chemotherapeutic agent. The aim of this
study was to evaluate the feasibility and overall survival (OS) of MET compared
to sorafenib for advanced hepatocellular carcinoma (HCC) patients with portal
vein tumor thrombosis (PVTT). METHODS: A total of 54 patients with advanced HCC
and PVTT who had undergone MET were analyzed between 2005 and 2013. A total of 53
patients who had undergone sorafenib therapy were analyzed as the control group.
The primary endpoint of this study was OS. RESULTS: The median number of MET
cycles was two (1-15). The OS values for the MET group and sorafenib group were
158 days (132-184) and 117 days (92-142), respectively (P=0.029). The Cox
proportional-hazard model showed that a higher risk of death was correlated with
higher serum alpha fetoprotein level (>=400 mg/dL, hazard ratio [HR]=1.680,
P=0.014) and Child-Pugh class B (HR=1.856, P=0.008). CONCLUSIONS: MET was
associated with more favorable outcomes in terms of overall survival than was
sorafenib in patients with advanced HCC with PVTT, especially in patients with
poor liver function. Therefore, MET can be considered as a treatment option in
patients with advanced HCC with PVTT and poor liver function.
PMID- 28494529
TI - NASH Therapy: omega 3 supplementation, vitamin E, insulin sensitizers and statin
drugs.
AB - Non-alcoholic steatohepatitis (NASH) is the more aggressive form of non-alcoholic
fatty liver disease (NAFLD). NASH can progress to hepatic fibrosis, cirrhosis,
portal hypertension and primary liver cancer. Therapy is evolving with a
substantial number of trials of promising new agents now in progress. In this
article however, we will examine data for several older forms of therapy which
have been fairly extensively studied over the years: Polyunsaturated Fatty Acid
(PUFA) supplements, vitamin E, insulin sensitizing agents with a focus on
pioglitazone and statin agents. Early interest in PUFA derived from their
potential benefit in cardio-metabolic disease and the close association of
NAFLD/NASH with Metabolic Syndrome. Results have been variable although most
studies show reduction of liver fat without other major effects and their effects
are influenced by concomitant weight loss and underlying genetic factors. Vitamin
E has had some efficacy in pediatric NASH but questionable efficacy in even mild
NASH among adults. Pioglitazone has shown significant histological benefit in a
number of trials but concern over side-effects (especially weight gain) have
dampened enthusiasm. A newer insulin sensitizer, liraglutide, has also shown
promise in a small randomized, controlled trial. Very limited data exists
regarding the histological effects of the statins in NASH and these agents appear
to be fairly neutral with neither clear cut benefit nor detriment. Their use is
best guided by cardiovascular risks rather than liver histology.
PMID- 28494530
TI - Radioembolization for the treatment of hepatocellular carcinoma.
AB - Transarterial radioembolization (TARE) with yttrium 90 (90Y), an intra-arterial
procedure performed by interventional radiologists, has begun being utilized in
managing hepatocellular carcinoma (HCC) in Korea. There are two available TARE
products: glass and resin microspheres with different physical characteristics.
All patients undergoing TARE must be assessed with clinical examination and
laboratory tests as well as a thorough angiographic evaluation. TARE is safe and
effective in the treatment of unresectable HCC, as it has longer time-to
progression, greater ability to downsize tumors for liver transplantation, less
post-embolization syndrome, and shorter hospitalization compared with
chemoembolization. TARE can also serve as an alternative to ablation, surgical
resection, portal vein embolization, and sorafenib. The utility of TARE continues
to expand with new insights in interventional oncology.
PMID- 28494531
TI - Stages of Adoption for Fecal Occult Blood Test and Colonoscopy Tests for
Colorectal Cancer Screening in Korea.
AB - PURPOSE: While colorectal cancer (CRC) is common in Asian countries, screening
for CRC is not. Moreover, CRC screening behaviors in Asian populations remain
largely unknown. The present study aimed to investigate the stages of adopting
CRC screening in Korea according to screening modality. MATERIALS AND METHODS:
Data were obtained from the 2014 Korean National Cancer Screening Survey, a cross
sectional survey that utilized nationally representative random sampling to
investigate cancer screening rates. A total of 2,066 participants aged 50-74
years were included in this study. Chi-square test and multinomial logistic
regressionwere applied to determine stages of adoption for fecal occult blood
test (FOBT) and colonoscopy and factors associated with each stage. RESULTS: Of
1,593 participants included in an analysis of stage of adoption for FOBT, 36%
were in action/maintenance stages, while 18%, 40%, and 6% were in
precontemplation, contemplation, and relapse/relapse risk stages, respectively.
Of 1,371 subjects included in an analysis of stage of adoption for colonoscopy,
48% were in action/maintenance stages, with 21% in precontemplation, 21% in
contemplation, and 11% in relapse/relapse risk stages. Multinomial logistic
regression highlighted sex, household income, place of residency, family history
of cancer, having private cancer insurance, smoking status, alcohol use, and
regular exercise as being associated with stages of adoption for FOBT and
colonoscopy. CONCLUSION: This study outlines the distributions of stages of
adoption for CRC screening by screening modality. Interventions to improve
screening rates should be tailored to individuals in particular stages of
adoption for CRC screening by modality.
PMID- 28494532
TI - Risk of Second Primary Cancer in People with Non-melanoma Skin Cancer: A
Nationwide Cohort Study.
AB - PURPOSE: Previous western studies have found Caucasians with skin cancer, either
melanoma or nonmelanoma skin cancer (NMSC), have an elevated risk of second
primary cancer. Our objective was to assess the risk of second primary cancer in
Taiwanese with NMSC. MATERIALS AND METHODS: By using data from Taiwan's National
Health Insurance Research Database, we conducted a population-based cohort study
to assess the risk of incident second primary cancer in Taiwanese affected by
NMSC. RESULTS: We identified 505 subjects with NMSC and 2,020 matched controls.
After adjustment for potential confounders including age, sex, urbanization, and
Charlson Comorbidity Index, people who had NMSC had a 1.43-fold (95% confidence
interval [CI], 1.05 to 1.96) risk for the development of second primary cancer as
comparedwith control group. Menwith NMSC had a 2.99-fold (95% CI, 1.00 to 9.10)
risk for second primary cancer involving the lip, oral cavity, and pharynx and a
3.51-fold (95% CI, 1.21 to 10.17) risk for second primary cancer involving the
genitourinary organs when compared to the control group. By contrast, women with
NMSC did not have an increased risk of second primary cancer. CONCLUSION: This
study revealed Asians with NMSC have an increased risk of second primary cancer.
Our findings can be a useful reference for health care for people diagnosed with
NMSC.
PMID- 28494533
TI - Awareness of and Attitudes toward Human Papillomavirus Vaccination among Adults
in Korea: 9-Year Changes in Nationwide Surveys.
AB - PURPOSE: Human papillomavirus (HPV) vaccination has been included in the National
Immunization Program in Korea since 2016. We aimed to evaluate changes in the
awareness of and attitudes toward HPV vaccination, among adults in Korea since
the first introduction of the vaccines in 2007. MATERIALS AND METHODS: A
nationwide population-based survey was conducted in 2016 for 1,200 nationally
representative Korean men and women; the data obtained were compared with the
data from the nationwide survey conducted in 2007. RESULTS: A significant
increase in the awareness of HPV infection (35.8%) and vaccination (36.9%) was
observed in 2016 from 13.3% and 8.6% in 2007, respectively. Willingness to be
vaccinated against HPV decreased from 55.0% in 2007 to 25.8% in 2016, and the
proportion of respondents expressing uncertainty increased from 28.3% in 2007 to
43.3% in 2016. Only 12.1% of men and 22.0% of women knew about the free national
HPV vaccination program for girls, launched in June 2016. Younger women, with
higher income level, awareness of the HPV vaccine, and perception of the
seriousness of infections had a higher willingness to be vaccinated. A high
education level, awareness of HPV infection and vaccination, and perception of
the seriousness of infection were positively associated with the willingness of
respondents to vaccinate their daughters. CONCLUSION: Raising the awareness of
HPV infection and vaccination with appropriate knowledge is necessary for the
successful implementation of the national HPV vaccination program.
PMID- 28494534
TI - Ferroptosis: A Novel Anti-tumor Action for Cisplatin.
AB - PURPOSE: Ferroptosis is a new mode of regulated cell death, which is completely
distinct from other cell death modes based on morphological, biochemical, and
genetic criteria. This study evaluated the therapeutic role of ferroptosis in
classic chemotherapy drugs, including the underlying mechanism. MATERIALS AND
METHODS: Cell viabilitywas detected by using the methylthiazoltetrazlium dye
uptake method. RNAiwas used to knockout iron-responsive element binding protein
2, and polymerase chain reaction, western blot was used to evaluate the
efficiency. Intracellular reduced glutathione level and glutathione peroxidases
activitywere determined by related assay kit. Intracellularreactive oxygen
species levelswere determined by flowcytometry. Electron microscopywas used to
observe ultrastructure changes in cell. RESULTS: Among five chemotherapeutic
drugs screened in this study, cisplatin was found to be an inducer for both
ferroptosis and apoptosis in A549 and HCT116 cells. The depletion of reduced
glutathione caused by cisplatin and the inactivation of glutathione peroxidase
played the vital role in the underlying mechanism. Besides, combination therapy
of cisplatin and erastin showed significant synergistic effect on their anti
tumor activity. CONCLUSION: Ferroptosis had great potential to become a new
approach in anti-tumor therapies and make up for some classic drugs, which open
up a new way for their utility in clinic.
PMID- 28494535
TI - TAK-264 (MLN0264) in Previously Treated Asian Patients with Advanced
Gastrointestinal Carcinoma Expressing Guanylyl Cyclase C: Results from an Open
Label, Non-randomized Phase 1 Study.
AB - PURPOSE: This phase 1 dose-escalation portion of the study evaluated the safety,
pharmacokinetics (PK), and antitumor activity of TAK-264 in Asian patients with
advanced gastrointestinal (GI) carcinoma or metastatic or recurrent gastric or
gastroesophageal junction adenocarcinoma expressing guanylyl cyclase C (GCC).
MATERIALS AND METHODS: Adult patients with advanced GI malignancies expressing
GCC (H-score >= 10) received TAK-264 on day 1 of 3-week cycles as 30-minute
intravenous infusions for up to 1 year or until disease progression or
unacceptable toxicity. The primary objectives were to evaluate the safety profile
including dose-limiting toxicities (DLTs) during cycle 1, determine the maximum
tolerated dose (MTD), and characterize the PK profile of TAK-264. RESULTS: Twelve
patients were enrolled and treated with 1.2 mg/kg (n=3), 1.5 mg/kg (n=3), or 1.8
mg/kg TAK-264 (n=6). Median number of treatment cycles received was two (range, 1
to 10). None of the patients experienced a DLT and the MTD was not determined.
Ten patients (83%) experienced adverse events (AEs). The most common were
neutropenia, anorexia, and nausea (each reported by four patients). Five patients
(42%) experienced grade >= 3 AEs consisting of tumor hemorrhage and hypertension,
ascites, adrenal insufficiency, neutropenia and asthenia. Serum exposure to TAK
264 increased proportionally with the dose and the median half-life was
approximately 5.5-6.6 days. No patients experienced an objective response.
CONCLUSION: TAK-264 demonstrated a manageable safety profile with limited
antitumor activity consistent with studies conducted in Western patients with
advanced GI malignancies. TAK-264 exposure increased proportionally with the
dose.
PMID- 28494536
TI - Clinical Significance of Discordance between Carcinoembryonic Antigen Levels and
RECIST in Metastatic Colorectal Cancer.
AB - PURPOSE: The purpose of this study was to investigate the prognostic implications
of carcinoembryonic antigen (CEA) levels that are inconsistent with Response
Evaluation Criteria in Solid Tumor (RECIST) responses in metastatic colorectal
cancer patients. MATERIALS AND METHODS: We retrospectively evaluated 360 patients
with at least one measurable lesion who received first-line palliative
chemotherapy. CEA-response was defined as CEA-complete response (CR; CEA
normalization), CEA-partial response (PR; >= 50% decrease in CEA levels), CEA
progressive disease (PD; >= 50% increase in CEA levels), and CEA-stable disease
(SD; non-CR/PR/PD). Overall survival (OS) and progression-free survival (PFS)
were evaluated according to CEA-response. RESULTS: In RECIST-PR patients, poorer
CEA-response was associated with disease progression at the subsequent
evaluation. In RECIST-SD patients, CEA-CR and -PR were associated with lower
disease progression rates than CEA-PD at the subsequent evaluation. Correlations
between survival outcome and CEA-response in same-category RECIST patients were
assessed. In RECIST-PR patients, discordant CEA-response (CEA-PD/SD) was
associated with poorer survival than CEA-CR/PR (median OS and PFS, 44.0 and 15.4
[CEA-CR], 28.9 and 12.5 [CEA-PR], 21.0 and 9.8 [CEA-SD], and 13.0 and 7.0 [CEA
PD] months, respectively; all p < 0.001). In RECIST-SD patients, favorable CEA
response produced better survival (median OS and PFS, 26.8 and 21.0 [CEA-CR],
21.0 and 11.0 [CEA-PR], 16.1 and 8.2 [CEA-SD], and 12.2 and 6.0 [CEA-PD] months,
respectively; all p < 0.001). RECIST-PD patients with CEA-CR showed longer OS
than those with CEA-PD. Multivariate analysis demonstrated that discordant CEA
response is a powerful prognostic factor for RECIST-PR and RECIST-SD patients.
CONCLUSION: Among patients of the same RECIST-response categories, CEA-response
patterns are significantly prognostic and strongly predictive of subsequent
evaluation outcomes.
PMID- 28494537
TI - Interstitial Lung Disease and Lung Cancer Development: A 5-Year Nationwide
Population-Based Study.
AB - PURPOSE: In this nationwide 5-year longitudinal population-based study, we aimed
at investigating the incidence of lung cancer among patients with interstitial
lung disease. MATERIALS AND METHODS: Data was collected from the Korean National
Health Insurance Research Database from 49,773,195 Korean residents in 2009.
Thirteen thousand six hundred and sixty-six patients with interstitial lung
disease diagnosed January-December 2009. The end of follow-up was June 30, 2014.
Up to four matching chronic obstructive pulmonary disease controls were selected
to compare the lung cancer high-risk group based on age, sex, diagnosis date
(within 30 days), and hospital size. The number of patients with newly developed
lung cancer was determined. RESULTS: The incidences of lung cancer were 126.98,
156.62, and 370.38 cases per 10,000 person-years (2,732, 809, and 967 cases of
cancer, respectively) in the chronic obstructive pulmonary disease, interstitial
lung disease, and chronic obstructive pulmonary disease with interstitial lung
disease groups, respectively. Of the 879 patients with idiopathic pulmonary
fibrosis, 112 developed lung cancer (incidence, 381.00 cases per 10,000 person
years). CONCLUSION: Incidence of lung cancer among patients with interstitial
lung disease was high. Interstitial lung diseases have a high potential for
developing into lung cancer, even when concurrent with chronic obstructive
pulmonary disease.
PMID- 28494538
TI - The exposome and the future of epidemiology: a vision and prospect.
AB - It is widely accepted that a relatively small proportion of chronic disease can
be explained by genetic factors alone. Although information about environmental
exposure is important to comprehensively evaluate chronic diseases, this
information is not sufficiently or accurately assessed by comparison with genomic
factors. To emphasize the importance of more complete evaluation of environmental
exposure, the concept of the exposome, which indicates the entirety of
environmental exposure from conception onwards, was introduced in 2005. Since the
2010s several epidemiological studies, such as the Human Early-Life Exposome
project, have applied the exposome concept. The exposome consists of three
overlapping domains: the general external, the specific external, and the
internal environments. General external factors include the broader socioeconomic
environment, and specific external factors include lifestyles, occupations, and
pollutant exposures. Internal factors include biological effects and responses.
Because the exposome covers exposures from conception to death, the birth cohort
is an important part of the exposome study. Although there is not yet an
established consensus in selecting what, when, and where to measure concerning
the exposome, the use of omics analyses, especially analysis of the metabolome,
should be considered in order to implement the exposome concept in the birth
cohort. The exposome needs to be measured repeatedly in certain important phases
of life, such as during pregnancy and infancy. To perform exposome-informed
epidemiological studies, untargeted data-driven approaches in conjunction with
dimension reduction techniques need to be developed and refined. The exposome
concept has the potential to make a breakthrough in overcoming some of the
limitations of conventional epidemiology. Concerted national and international
efforts are required for future exposome studies.
PMID- 28494539
TI - [Current status and perspectives of diagnosis and treatment of complications
related to liver cirrhosis].
AB - Liver cirrhosis is the severe period of chronic liver diseases, especially
decompensated liver cirrhosis and its complications, such as ascites,
esophagogastric variceal bleeding, hepatic encephalopathy, acute kidney injury,
and hepatocellular carcinoma, which greatly affect patients' quality of life and
even threaten their lives. Early prevention and treatment of the causes of
development and progression and pathogenic mechanism may slow down or reverse
liver cirrhosis and its severe complications. Once the disease progresses to
portal hypertension and related complications, it is very important to select
preventive measures for acute exacerbation of different complications, as well as
the methods and timing for treatment in acute stage, which may help to save
patients' lives and improve their prognosis.
PMID- 28494540
TI - [Research advances in pathophysiology and diagnosis and treatment of hepatorenal
syndrome].
AB - Hepatorenal syndrome (HRS) is functional renal injury in patients with liver
cirrhosis or fulminant liver failure and is one of the complications of
progressive liver failure which threatens patients' lives. With the progression
of liver diseases, hemodynamic disturbance may eventually cause HRS. Achievements
have been made in the pathophysiology, diagnostic criteria, and treatment of HRS.
This article introduces the research advances in the pathophysiology, diagnosis,
and treatment of HRS.
PMID- 28494541
TI - [New therapeutic paradigm and concepts for patients with cirrhotic refractory
ascites].
AB - The activation of renin-angiotensin-aldosterone-vasopressin system is a key
factor in the formation of ascites due to splanchnic vasodilation in cirrhosis.
In theory, aldosterone antagonists, contraction of blood vessels, vasopressin V2
receptor, and angiotensin receptor antagonists are important targets for the
prevention and treatment of cirrhotic ascites. The 15%-20% of patients with
cirrhotic ascites that show no response to at least one week's treatment with
potent diuretics (spironolactone 160 mg/d combined with furosemide 80 mg/d) are
considered to have refractory ascites. At present, effective treatments for
refractory ascites include tolvaptan, large-volume paracentesis (4000-6000
ml/time/day) combined with albumin (4 g/L ascites), ascites ultrafiltration and
reinfusion, transjugular intrahepatic portosystemic shunt, and liver
transplantation. In the future, with the development of vasoactive drugs,
rifaximin, ascites drainage pump, and other new therapies, the treatment of
refractory ascites may be more effective to reduce the need for liver
transplantation.
PMID- 28494542
TI - [Management algorithm for interrupting mother-to-child transmission of hepatitis
B].
PMID- 28494543
TI - [Effects of Anluohuaxianwan on transforming growth factor-beta1 and related
signaling pathways in rats with carbon tetrachloride-induced liver fibrosis].
AB - Objective: The traditional Chinese medicine Anluohuaxianwan (ALHXW) has been used
to treat liver fibrosis induced by chronic hepatitis B virus (HBV) infection.
However, the anti-fibrosis mechanisms of ALHXW remain to be investigated. This
study used a rat model of carbon tetrachloride (CCl(4))-induced liver fibrosis to
explore the potential antifibrogenic mechanisms of ALHXW. Methods: Twenty-seven
male Wistar rats were randomly assigned to control group, model group, and
treatment group (n = 9 per group). Rats in the model and treatment group were
injected intraperitoneally with 40% CCl(4)(2 ml/kg), and rats in the control
group were administered saline twice a week for 6 weeks. Starting at week 4
following model construction, rats in the treatment group received daily gavages
with ALHXW solution (concentration 0.15 g/ml) daily, while rats in the control
and model groups were given saline for a total of 6 weeks. Alanine
aminotransferase (ALT) and aspartate aminotransferase (AST) were measured from
blood samples collected at the end of weeks 3, 6 and 9. Histopathological
examination of liver tissue was performed to evaluate liver fibrosis at week 9.
At the same time, the mRNA expression of TGF-beta1 and Smads in liver tissues was
quantified by real-time reverse transcription polymerase chain reaction (RT-PCR),
and TGF-beta1 protein level in the liver was measured by Western blot. Inter
group comparison was performed using analysis of variance (ANOVA) when the
continuous data were normally distributed and satisfied the homogeneity of
variance; otherwise, nonparametric tests were used. Categorical data were
compared between groups using nonparametric tests. Results: ALHXW markedly
alleviated liver injury in the treatment group after 3 weeks of therapy as
indicated by a significantly reduced level of ALT compared with the model group
[(162.98 +/- 73.14)U/L vs (322.52 +/- 131.76)U/L, P = 0.047], and a 39.8%
reduction in AST level compared with the model group[ (537.56 +/- 306.06)U/L vs
(892.98 +/- 358.19)U/L, P = 0.053]. Moreover, at the end of the 6-week therapy,
histopathological diagnosis showed that liver fibrosis was significantly reduced
in the ALHXW-treated group compared with that in the model group (P = 0.002). The
relative expression of TGF-beta1 mRNA and protein in the liver were significantly
lower in ALHXW-treated rats than that in model rats (1.34 +/- 0.31 vs 1.78 +/-
0.45, P = 0.025; 0.39 +/- 0.02 vs 0.57 +/- 0.04, P = 0.003). Conclusion: ALHXW
treatment can reverse CCl(4)-induced liver fibrosis in rats. Its mechanisms of
anti-fibrosis may occur through the inhibition of TGF-beta1 synthesis and TGF
beta1/Smads signaling pathway, which in turn suppress the activation of hepatic
stellate cells and thereby reverses fibrosis.
PMID- 28494544
TI - [Association between high expression of intrahepatic programmed death-1 and liver
inflammation in patients with autoimmune hepatitis].
AB - Objective: To investigate the expression of programmed death-1 (PD-1) in liver
tissue and its association with liver pathology in patients with autoimmune
hepatitis (AIH). Methods: A total of 54 AIH patients (38 in the active stage and
16 in the remission stage) were enrolled, and 9 healthy volunteers were enrolled
as control group. Immunohistochemistry combined with quantitative image analysis
was used to measure the expression of PD-1 in liver tissue. The t-test, rank sum
test, one-way analysis of variance, least significant difference t-test, Mann
Whitney U test, and Pearson relation analysis were used for statistical analysis
of different types of data. Results: The AIH group had a significantly higher
positive rate of PD-1 in liver tissue than the control group (13.57%+/-6.84% vs
2.22%+/-0.66%, P < 0.01), and the patients in the active stage of AIH had a
significantly higher positive rate of PD-1 in liver tissue than those in the
remission stage (16.53%+/-7.72% vs 6.56%+/-3.16%, P < 0.01). The positive rate of
PD-1 in liver tissue was 6.56%+/-3.16% in G0 group, 14.33%+/-5.08% in G1-2 group,
and 19.23%+/-5.41% in G3-4 group (P < 0.01), but there was no significant
difference in the positive rate of PD-1 between S0, S1-2, and S3-4 groups (P >
0.05). In AIH patients, the positive rate of PD-1 in liver tissue was positively
correlated with the levels of total bilirubin, alanine aminotransferase,
aspartate aminotransferase, and IgG (r = 0.665, 0.721, 0.711, and 0.813, all P <
0.01). Conclusion: AIH patients have regulated PD-1 expression in liver tissue,
which is closely associated with liver inflammation and is not associated with
fibrosis degree, suggesting that PD-1 is involved in the development and
progression of inflammation in AIH patients.
PMID- 28494545
TI - [Regulatory effect of faciogenital dysplasia 6 gene on hepatic stem cell
differentiation].
AB - Objective: To investigate the regulatory effect of faciogenital dysplasia 6
(FGD6) gene on hepatic stem cell differentiation. Methods: FGD6 gene was selected
for the co-intervention of target sequence, the AdEasy system was used for the
construction of adenovirus vector and the packaging and multiplication of the
recombinant adenovirus vector pSES-FGD6-siRNA, and the HP14.5 cells were
infected. Immunofluorescence assay was used to measure the expression of FGD6
protein in HP14.5 cells, quantitative real-time PCR was used to measure the mRNA
expression of FGD6, alpha-fetoprotein (AFP), and albumin (Alb), and Western blot
was used to measure the protein expression of FGD6, AFP, and Alb. The empty pSES
Ad-RFP adenovirus vector was constructed as control in each group. All data were
expressed as x+/-s, and a one-way analysis of variance was performed. Results:
FGD6 protein was mainly expressed in the nucleus of HP14.5 cells. The pSES-FGD6
siRNA adenovirus vector was successfully constructed and it downregulated the
expression of FGD6 gene and the mRNA and protein expression of AFP in HP14.5
cells and upregulated the mRNA and protein expression of Alb (P < 0.01).
Conclusion: The inhibition of the expression of FGD6 gene in HP14.5 cells may
differentiate HP14.5 cells into hepatocytes. Therefore, FGD6 gene plays an
important role in the differentiation regulation of hepatic stem cells.
PMID- 28494546
TI - [Regulatory effect of bone marrow mesenchymal stem cells on polarization of
macrophages].
AB - Objective: To examine the regulatory effect of bone marrow mesenchymal stem cells
(BM-MSCs) on the polarization of bone marrow-derived macrophages, and to provide
a theoretical support for the application of mesenchymal stem cells in the
treatment of liver fibrosis. Methods: MSCs and macrophages were first isolated
from the bone marrow of mice. Macrophages were polarized to M1 macrophages with
lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma), and to M2 macrophages
with interleukin-4 (IL-4). The macrophages were then co-cultured with BM-MSCs in
a Transwell for 24 h, and changes in the percentages of M1 and M2 macrophages
were examined using flow cytometry. The mRNA levels of the M1 macrophage
associated cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-23a
(IL-23a), and M2 macrophage-associated molecules, arginase-1 (Arg-1) and CD163,
were measured by real-time quantitative PCR. The two samples were compared using
the t test, and P < 0.05 was considered as statistically significant. Results:
Flow cytometry showed that the percentage of M1 macrophages was significantly
lower in the (macrophage + LPS + IFN-gamma + BM-MSC) co-culture group than in the
(macrophage + LPS + IFN-gamma) group (62.5% +/- 4.6% vs 86.6% +/- 6.9%, t =
5.034, P = 0.0073). In addition, the relative mRNA expression of TNF-alpha and IL
23a was also significantly reduced in the co-culture group compared with those in
the macrophage control group as measured by RT-qPCR (t = 11.57 and 10.57,
respectively, P < 0.05). Compared with that in the macrophage control group, the
percentage of M2 macrophages in the (macrophage+BM-MSC) co-culture group was
significantly increased (89.5% +/- 5.8% vs 70.1% +/- 6.3%, t = 3.924, P =
0.0172), along with significantly elevated relative mRNA expression of Arg1
(14.35+/-1.05 vs 1.00+/-0.03, t = 21.96, P < 0.05) and CD163 (3.04 +/- 0.27 vs
1.00 +/- 0.03, t = 13.14, P < 0.05). Conclusion: BM-MSCs can inhibit LPS + IFN
gamma-induced polarization to M1 macrophages and promote polarization to M2
macrophages through the release of paracrine factors.
PMID- 28494547
TI - [Dynamic expression of carnitine palmitoyltransferase II in the mitochondrial
inner membrane during hepatocyte malignant transformation induced by lipid
accumulation].
AB - Objective: To investigate the dynamic expression of hepatic carnitine
palmitoyltransferase-II (CPT-II) in the mitochondrial inner membrane during
hepatocyte malignant transformation induced by lipid accumulation. Methods: Male
Sprague-Dawley rats were divided randomly into control, fatty liver, and induced
cancer groups, which were fed with normal, high-fat (HF), and HF containing 2
fluorenylacetamide (0.05%, 2-FAA) diets, respectively, for 14 weeks. One rat from
each group was sacrificed every two weeks and the blood and liver samples were
collected. Liver morphological changes were evaluated with hematoxylin and eosin
staining, and the liver tissue samples were divided into control, fatty liver,
degeneration, precancerous, and cancerous groups accordingly. Hepatic lipids were
dyed by the oil red O method. The CPT-II expression was measured by
immunohistochemistry and compared with the specific CPT-II concentration (ng/mg
liver protein, ng/mg P) among different groups. Serum levels of circulating total
cholesterol (Tch), triglyceride (TG), alanine aminotransferase (ALT), and
aspartate aminotransferase (AST) were quantitatively analyzed. Results: Massive
lipid accumulation hepatocytes was seen in rats on HF and HF containing 2-FAA
diets. The lipid levels in the control group were significantly lower than those
in the fatty liver (t = -11.556, P < 0.001), degeneration (t = -4.847, P = 0.04),
precancerous (t = -13.652, P = 0.005), and cancerous groups (t = -10.896, P =
0.008). The serum TG and Tch levels in the degeneration, precancerous, and
cancerous groups were 2-3 times higher than those in the control group (P <
0.05). After 2-FAA treatment, the morphological changes of rat hepatocytes showed
the progression from degeneration and precancerosis to cancerosis, with
hepatocyte injury. The serum AST and ALT levels in the degeneration,
precancerous, and cancerous groups were significantly higher (4-8 times) than
those in the control group (P < 0.05). The specific concentration of liver CPT-II
expression was significantly reduced during hepatocyte malignant transformation,
as confirmed by immunohistochemistry, with the CPT-II levels significantly lower
in the cancerous group than in any of other groups (P < 0.05). Conclusion: Low
hepatic CPT-II expression might lead to abnormal lipid accumulation in
hepatocytes, which should promote the malignant transformation of hepatocytes.
PMID- 28494548
TI - [The role of cytochrome P450 in nonalcoholic fatty liver induced by high-fat
diet: a gene expression profile analysis].
AB - Objective: To clarify the role of cytochrome P450 in nonalcoholic fatty liver
disease (NAFLD) by RNA-Seq and bioinformatics analysis. Methods: A total of 20
male C57BL/6 mice were used. Ten mice were fed with high-fat diet (D12492, 60%
kcal fat) for 16 weeks to establish a mouse model of NAFLD, and the other 10 mice
were fed with low-fat diet (D12450B, 10% kcal fat) as control group. At the end
of the experiment, the body weight, liver weight, and hepatic triglyceride (TG)
content were measured. Meanwhile, HE staining and RNA-Seq analysis were performed
for the liver tissues. The differentially expressed genes were screened out and
subjected to bioinformatics analysis, including KEGG and GO BP enrichment
analyses and interaction network analysis. Comparison of means between the two
groups was made using t-test. Results: Compared with the control group, the mice
in the model group were obviously obese, with significantly increased body weight
(41.41 +/- 6.01 g vs 28.78 +/- 1.79 g, t = 6.04, P < 0.01) and liver weight (1.38
+/- 0.30 g vs 1.08 +/- 0.10 g, t = 2.89, P < 0.01). The mice in the model group
showed obvious steatosis, accompanied by a small amount of inflammatory cell
infiltration, but with no obvious fibrosis, according to the results of HE
staining. In addition, the hepatic TG content in the model group was
significantly increased compared with that in the control group (0.64 +/- 0.01
mg/mg vs 0.29 +/- 0.06 mg/mg, t = 10.11, P = 0.04). Compared with the control
group, a total of 367 differentially expressed genes, including 211 down
regulated and 156 up-regulated ones, were identified in the model group according
to the RNA-seq results. Meanwhile, 19 CYP450 subtypes, accounting for 5% of the
differentially expressed genes, were identified, and CYP2E1, CYP2C70, CYP3A11,
CYP3A25, CYP2D26, CYP4A10, CYP17A1, CYP2B10, and CYP2C38 were involved in
oxidative stress, steroid hormone metabolism, fatty acid metabolism, arachidonic
acid metabolism, and the PPAR signaling pathway. An interaction network was
constructed with 30 nodes, and CYP2E1 and CYP2C70 were identified as key nodes.
RT-PCR validation results showed that the expression changes of CYP450 subtypes
and lipid metabolism-related genes were consistent with the findings of
sequencing. Conclusion: The CYP450 family plays a vital role in the pathogenesis
of fatty liver by regulating lipid metabolism-related pathways, including
oxidative stress, arachidonic acid metabolism, steroid hormone metabolism , and
fatty acid metabolism.
PMID- 28494549
TI - [Changes in the composition of intestinal microbiota in mice with acute liver
failure induced by D-galactosamine].
AB - Objective: To investigate the changes in the composition of intestinal microbiota
in mice with acute liver failure and identify characteristic bacteria, and to
provide a basis for the diagnosis and treatment of acute liver failure with
intestinal microbiota disorders. Methods: A total of 30 specific pathogen-free
male BALB/c mice were used in this study, including 25 mice in the model group
and 5 mice in the control group. An acute liver failure model was induced by D
galactosamine. Microbial DNA was extracted from intestinal contents in different
segments of the lower digestive tract (ileum and colon) and feces and then were
amplified using PCR. The regions of 16S V3-V4 were subjected to high-throughput
sequencing, followed by bioinformatics analyses, including OTU hierarchical
clustering, species annotation, alpha-diversity analysis, and LEfSe (LDA Effect
Size) analysis. Comparison of continuous data was made using t-test, while
comparison of categorical data was made using chi2 test. Results: A total of 10
mice survived in the two groups, with 80% mortality rate in the model group. The
alpha-diversity analysis revealed increased bacterial diversity and abundance in
the ileum, increased bacterial diversity and reduced bacterial abundance in the
colon, and reduced bacterial diversity and insignificantly changed bacterial
abundance in feces in the model group compared with the control group. Based on
the optimized classification level, significantly reduced abundance of
Clostridiaceae (44.95% +/- 19.28% vs 7.51% +/- 16.57%, P = 0.011) in the ileum,
whereas significantly increased abundance of Rikenellaceae (1.08% +/- 1.01% vs
4.18% +/- 2.39%, P = 0.028), S24-7 (4.75% +/- 4.87% vs 22.77% +/- 13.05%, P =
0.020), and F16 (0.24% +/- 0.28% vs 2.18% +/- 1.61%, P = 0.029) in the colon were
found in model group compared with the control group. The LEfSe analysis
demonstrated that there were significant differences in Staphylococcaceae and S24
7 between the two groups, and S24-7 could be defined as the characteristic
bacteria. Conclusion: Intestinal microbiota disorders, especially the excessive
growth of microbes in the ileum, are observed in mice with acute liver failure.
Moreover, acute liver failure may be closely associated with the excessive growth
of S24-7.
PMID- 28494550
TI - [Regulatory effect of vitamin D on proliferation and apoptosis of hepatic
stellate cells].
PMID- 28494551
TI - [Value of liver transplantation in treatment of angiosarcoma: a report of 2
cases].
PMID- 28494552
TI - [Liver cirrhosis with liver hemochromatosis: a case report].
PMID- 28494553
TI - [Glycogenosis type IX caused by a novel mutation of phosphorylase kinase alpha
subunit: a family analysis].
PMID- 28494554
TI - [Minutes of the 26th Conference of the Asian Pacific Association for the Study of
the Liver].
PMID- 28494555
TI - [Liver sinusoidal endothelial cells regulate adaptive immune tolerance in the
liver].
AB - Liver sinusoidal endothelial cells are a major group of nonparenchymal cells in
the liver and are involved in immunological surveillance of the liver through the
expression of various scavenger receptors and pattern recognition receptors.
However, in case of several physiological states, viral infections, and tumor
environment, liver sinusoidal endothelial cells maintain immune tolerance in the
liver through various mechanisms and cause persistent viral infection and tumor
metastasis. This article reviews the mechanisms of immune tolerance of CD4 + T
cells and CD8 + T cells in the liver induced by liver sinusoidal endothelial
cells.
PMID- 28494556
TI - [Clinical value of health-related quality of life evaluation in community
patients with hepatitis B].
AB - Chronic hepatitis B (CHB) is a major infectious disease which threatens people's
health around the world. Health-related quality of life (HRQoL) has become an
important index for evaluating the treatment and prognosis of patients with CHB.
Many studies abroad have shown that the HRQoL of patients with CHB is influenced
by various factors. Disease severity, clinical symptoms, and low self-efficacy
are important influencing factors for patients' quality of life. Anti-viral
therapy, proper physical therapy, or psychological intervention can significantly
improve the HRQoL of community CHB patients, and HRQoL is even significantly
improved in patients undergoing liver transplantation one year ago. These studies
provide valid evidence for antiviral therapy for hepatitis B patients and liver
transplantation techniques from the psychological level. At present, there still
lacks studies on HRQoL of CHB patients in China. This article summarizes the
measurement tools for HRQoL widely used in recent years in China and foreign
countries, reviews the research advances in HRQoL in community patients with CHB,
and discusses the perspectives for future studies.
PMID- 28494557
TI - [Clinicopathologic features of drug-induced vanishing bile duct syndrome].
AB - Vanishing bile duct syndrome (VBDS) manifests as progressive destruction and
disappearance of the intrahepatic bile duct caused by various factors and
cholestasis. VBDS associated with drug-induced liver injury (D-VBDS) is an
important etiology of VBDS, and immune disorder or immune imbalance may be the
main pathogenesis. According to its clinical symptoms, serological markers, and
course of the disease, D-VBDS is classified into major form and minor form, and
its clinical features are based on various pathomorphological findings. Its
prognosis is associated various factors including regeneration of bile duct
cells, number of bile duct injuries, level and range of bile duct injury, bile
duct proliferation, and compensatory shunt of bile duct branches. This disease
has various clinical outcomes; most patients have good prognosis after drug
withdrawal, and some patients may experience cholestatic cirrhosis, liver
failure, and even death. Due to the clinical manifestation and biochemical
changes are similar to the primary biliary cholangitis (PBC) and primary
sclerosing cholangitis (PSC), it need to identify by clinical physician.
PMID- 28494558
TI - [Complications of minimally invasive vitreous surgery can not be ignored].
AB - Pars plana vitrectomy (PPV) has become an important means of treating complex
vitreoretinopathy, and the introduction of small-gauge PPV instrumentation and
techniques has even considerably widened the surgery choice. Though the small
gauge PPV systems have many advantages, ophthalmologists must realize that the
small-gauge PPV does not necessarily refer to minimally invasive PPV.
Ophthalmologists should not just pursue the small incision, ignore the principle
of minimally invasive PPV and the rational choice of indications, and
underestimate surgical risks and postoperative complications. Ophthalmologists
must be familiar with the advantages and limitations of minimally invasive PPV so
as to achieve the best therapeutic effects with minimized trauma. (Chin J
Ophthalmol, 2017, 53: 321-324).
PMID- 28494559
TI - [Comparative study of the effects of sterilized air and perfluoropropane gas
tamponades on recovery after idiopathic full-thickness macular hole surgery].
AB - Objective: To compare the effects of sterilized air and perfluoropropane
(C(3)F(8)) tamponades on recovery after vitrectomy for the treatment of
idiopathic full-thickness macular hole (IFTMH). Methods: Case control study.
Seventy-three eyes of 69 consecutive cases underwent vitrectomy with air (53
eyes) or 10% C(3)F(8) gas (20 eyes) tamponade. Surgical outcomes were
retrospectively analyzed between the two groups, including logarithm of the
minimal angle of resolution (logMAR) and optical coherence tomography findings
like the size of the macular hole and the photoreceptor layer defect. Results:
Preoperatively, the mean best corrected visual acuity (BCVA) was (0.10+/-0.49),
the mean hole diameter was (777.9+/-320.7) MUm, and the mean diameter of the
photoreceptor layer defect was (1 709.3+/-516.0) MUm in the sterilized air group,
while in the C(3)F(8) group, the mean BCVA was (0.07+/-0.50), the mean hole
diameter was (853.9+/-355.0) MUm, and the mean defect diameter was (1 480.5+/
429.9) MUm. The primary closure rate was 90.6% in the sterilized air group and
95.0% in the C(3)F(8) group. One month after surgery, the mean BCVA was (0.17+/
0.41), and the mean diameter of the photoreceptor layer defect was (820.5+/
598.0) MUm in the sterilized air group, while in the C(3)F(8) group, the mean
BCVA was 0.12+/-0.49, and the mean defect diameter was (762.5+/-658.0) MUm. There
was no statistically significant difference in the closure rate (chi(2)=0.019),
BCVA (t=-1.689), hole diameter (t=0.837) and diameter of the photoreceptor layer
defect (t=0.338) between the two groups(P>0.05). Conclusions: Vitrectomy with
sterilized air tamponade is safe and effective for the treatment of IFTMH and
even cases with relatively large diameters. (Chin J Ophthalmol, 2017, 53: 327
331).
PMID- 28494560
TI - [Visual impact of sub-tenon's anesthesia during surgery for retinal detachment].
AB - Objective: To investigate the visual impact and influence factors of sub-Tenon's
anesthesia in retinal detachment patients during pars plana vitrectomy (PPV) or
combined phacoemulsification and PPV surgery. Methods: In this prospective case
series study, 104 consecutive patients who underwent PPV or combined
phacoemulsification and PPV under sub-Tenon's anesthesia between October 2012 and
December 2013 were enrolled. Intraoperatively, the patients were asked whether
they could see the light of the operating microscope or not at 5 minutes after
sub-Tenon's anesthesia, and at the end of phacoemulsification, core vitreous
removal, peripheral vitreous removal and the whole surgery, with their
contralateral eyes being covered tightly and no photobleaching. The best
corrected visual acuity and visual evoked potentials were examined and compared
with each other preoperatively and at 1.5 months and 3 months postoperatively.
Chi-square test was used to compare the detection rate of amaurosis between
different modus operandi and whether covered contra-lateral eye. Student-t test
was used to compare the difference of age and preoperative BCVA between the
patients with or without experienced amaurois. Lastly, BCVA between different
times were tested by one-way ANOVA analysis. Results: Without covering the
contralateral eyes, the incidence of no light perception in various surgical
steps was 0%, while it was 72.1%(75/104), 93.8%(75/80), 96.2%(100/104),
96.2%(100/104) and 86.5%(90/104) at the five timepoints, respectively, when the
contralateral eyes were covered tightly. The incidence was 51.9%(54/104),
85.0%(68/80), 85. 6%(89/104), 84.6%(69/104) and 66.3%(88/104), respectively,
after photobleaching was excluded. Approximately 95.2%(99/104) of patients
reported no light perception at least once, 54.5%(54/99) reported no light
perception 5 minutes after sub-Tenon's anesthesia, and 30.3%(30/99) recovered
light perception when the surgery was finished. All eyes recovered to at least
light perception on the first postoperative day. The best corrected visual acuity
and visual evoked potentials at 1.5 months and 3 months postoperatively were
significantly better than those before surgery. The BCVA was 1.75+/-0.78
preoperative, 0.96+/-0.63 1.5 months after operation, and 0.92+/-0.57 3 months
after operation. There was a significant statistical difference between
preoperative BCVA and postoperative BCVA (F=50.61, P<0.01) . In patients without
waveform detection preoperatively, PVEP waveform could be found in 43.6% and
61.4% of the pactients at 1.5 months and 3 months after operation respectively.
In those had certain waveform preoperatively, PVEP amplitudes rise significantly
after surgery (t(1.5)=-2.69, t(3)=-2.97, P<0.05) . Conclusions: No light
perception was detected in various surgical steps of vitrectomy under sub-Tenon's
anesthesia in most patients. The blocking of optic nerve conduction may be caused
by sub-Tenon' s anesthesia. Photobleaching can also have some effect. The
incidence of no light perception during the surgery was not correlated with
preoperative visual acuity, age and gender. Moreover, the effect was transient
and harmless to visual function.(Chin J Ophthalmol, 2017, 53: 332-337).
PMID- 28494561
TI - [Observation of single-layered inverted internal limiting membrane flap technique
for macular hole with retinal detachment in high myopia].
AB - Objective: To compare the outcome of pars plana vitrectomy (PPV) with a single
layered inverted internal limiting membrane (ILM) flap versus PPV with ILM
peeling for the treatment of macular hole associated retinal detachment (MHRD) in
high myopia. Methods: In a retrospective cohort study, PPV with 2 kinds of
adjuvant surgical procedures were used in 35 moderately high myopia eyes with
MHRD. These eyes were divided into 2 groups: group 1 (17 eyes) receiving PPV and
ILM peeling and group 2 (18 eyes) receiving PPV with a single-layered inverted
ILM flap. Anatomical reattachment of the retina, macular hole closure, and best
corrected visual acuity (BCVA) were measured at 6 months after surgery. Results:
The retina was successfully reattached in all cases. The difference of the
retinal reattachment rate between the two groups was not statistically
significant (Fisher's exact test, P=1.000). The rate of macular hole closure was
47.1% in group 1 (8 eyes) and 88.9% in group 2 (16 eyes). The difference of the
macular hole closure rate between the two groups was statistically significant
(Fisher's exact test, P= 0.012). Significant improvement in logarithm of minimal
angle of resolution (logMAR) BCVA was achieved in both groups. There was no
difference in the initial, final, or improved logMAR BCVA in the 2 groups.
Conclusion: Single-layered inverted ILM flap technique effectively helps close
the macular hole in moderately high myopia with MHRD. This may prevent the
possible redetachment from the macular hole. (Chin J Ophthalmol, 2017, 53: 338
343).
PMID- 28494562
TI - [Intraoperative risk factors associated with visual acuity outcomes of pars plana
vitrectomy in idiopathic epiretinal membrane].
AB - Objective: To evaluate intraoperative risk factors related to the postoperative
visual acuity in idiopathic epiretinal membrane (IERM) . Methods: According to
the well-established study criterion, a retrospective observational study was
carried out on 37 eyes of 37 patients with epiretinal membrane peeling surgery
for IERM between January 2014 and January 2015. Intraoperative situations during
membrane peeling were documented, including complexity of operation, superficial
hemorrhage and the state of indocyanine green (ICG) staining. Best-corrected
visual acuity (BCVA) measurement and optical coherence tomography were performed
before and 1, 3, 6 and 12 months after surgery. Multifocal electroretinography
and fundus fluorescein angiography were conducted at 6 months postoperatively.
The patients were divided into two groups based on the BCVA (>=0.5 and<0.5) at 6
months after surgery. The BCVA was converted to logarithm of the minimum angle of
resolution (logMAR) equivalents for statistical analysis. The relationship
between intraoperative factors and postoperative visual acuity was analyzed by
multiple logistic regression analysis. Results: All patients completed follow-ups
in an average duration of (14.41+/-2.33) months. Among the 37 patients, 28
patients (75.7%) were in the BCVA >=0.5 group. and 9 patients (24.3%) were in the
BCVA<0.5 group. Statistical analysis revealed that superficial hemorrhage during
membrane peeling was associated with poor visual acuity after surgery (OR: 7.221,
95% CI: 1.775-29.372, P=0.006) . The peeling complexity was positively increased
with presence of superficial hemorrhage (gamma=0.336, P=0.042) and ICG staining
(gamma=0.593, P=0.000) . The electroretinography revealed that the average
latency of N1 wave at ring 1 in eyes with superficial hemorrhage (16.88+/-1.27)ms
was longer than that in eyes without superficial hemorrhage (12.80+/-4.21)ms at 6
months postoperatively (t=-2.187, P= 0.042). The fluorescein angiography showed 8
in 10 eyes with superficial hemorrhage had leakage on the macular fovea.
Conclusions: Superficial hemorrhage in IERM peeling is a risk factor for the poor
postoperative visual function. Complex peeling contributes to superficial
hemorrhage and the positive staining of ICG. (Chin J Ophthalmol, 2017, 53:344
351).
PMID- 28494563
TI - [The clinical manifestations and imaging characteristics of acute syphilitic
posterior placoid chorioretinitis].
AB - Objective: To investigate the clinical manifestations and imaging characteristics
of acute syphilitic posterior placoid chorioretinitis (ASPPC). Methods:
Retrospective study of 10 patients diagnosed ASPPC in the Department of
Ophthalmology, Beijing Tongren Hospital from 2011 to 2016, including 6 males (10
eyes involved) and 4 females (8 eyes involved) with an age of (43.4+/-11.6) years
(range, 26-60 years). Their clinical manifestations and imaging characteristics
were summarized. Results: All 10 ASPPC patients complained about the reduction of
visual acuity, and the majority of them had both eyes involved. The initial
visual acuity ranged from finger count to 0.8, with an average of 0.4 and a
median visual acuity of 0.3. The intraocular pressure was in the normal range.
The inflammation of anterior chamber occurred in only one patient (1/10). The
lesions were located at the posterior pole as shown on fundus photographs. There
are six placoid lesions, four yellowish massive lesions and seven mixed lesions
(placoid and yellowish massive lesions). Partial or whole disappearance,
abnormality and opacity of the ellipsoid layer, retinal pigment epithelial (RPE)
nodules, and cells in the vitreous body were observed by optical coherence
tomography. There were partial detachment between the neuronal retina and RPE
layer with fine-sand like hypereflective dots. The lesion size and morphology on
autofluorescence (AF), fundus fluorescence angiography (FFA) and indocyanine
green angiography (ICG) were almost consistent with those on fundus photography.
The lesions were hyperautofluorescent in a placoid or massive shape. The lesions
on FFA showed slight hyperfluorescence with unclear edges from the venous phase,
and the fluorescence increased with the time and leaked in the late phase.
Vascular walls showed blood staining in the late phase. The lesions on ICG showed
hypofluorescence with hyperfluorescence and hypofluorescence dots like fine
needles in the middle and late phases. Conclusion: ASPPC mainly occurs among the
young adults without gender difference. The characteristic is the contradiction
between sever clinical symptoms and slight signs on the fundus. The lesion area
shown on fundus photography, FFA, ICG and AF is consistent, as well as injuries
of the ellipsoid layer, RPE nodules and cells in the vitreous body. The above
manifestations and imaging characteristics of ASPPC are significant for the
diagnosis and differential diagnosis. (Chin J Ophthalmol, 2017, 53:352-357).
PMID- 28494564
TI - [Clinical observation and related factors analysis of neonatal asphyxia
complicated with retinal hemorrhage].
AB - Objective: To observe and analyze related factors of neonatal asphyxia
complicated with retinal hemorrhage. Methods: It was a retrospective case series.
Seven hundred and twenty-one cases with neonatal asphyxia after 72 hours of birth
were enrolled in this study. Fundus examination was performed on these newborns
using the third generation wide-angle digital retina imaging system (RetCamIII),
and the bleeding level was divided into level I, level II and level III. The
conditions of the newborn and the mother during pregnancy were correlatively
analyzed. The other factors were also analyzed including delivery mode, birth
weight, gestational age, gender, grade of neonatal asphyxia, scalp hematoma,
intracranial hemorrhage, fetal intrauterine distress, mother's age and antenatal
complications. Single factor chi(2) test and multivariate logistic regression
analysis were used to screen and judge risk factors causing retinal hemorrhage
related to neonatal asphyxia. Results: In 721 cases of neonatal asphyxia, retinal
hemorrhage was found in 204 newborns (28.29%). The hemorrhage was at level I in
77 cases (37.75%) , at level II in 38 cases (18.63%) and at level III in 89 cases
(43.63%) . Four cases also had vitreous hemorrhage. Asphyxia was mild in 673
infants (93.34%) and severe in 48 infants (6.66%). The difference in the degree
of retinal hemorrhage between the patients with mild and severe asphyxia was
significant (chi(2)=22.336, P=0.000). When asphyxia was aggravated, the degree of
retinal hemorrhage increased. Relative factors analysis showed that delivery mode
(chi(2)=158.643, P<0.05), gestational age (chi(2)=24.522, P<0.05), birth weight
(chi(2)=11.916, P<0.05) and grade of neonatal asphyxia (chi(2)=19.809, P<0.05)
had correlations with retinal hemorrhage. Logistic regression analysis indicated
that grade of neonatal asphyxia and delivery mode were risk factors of retinal
hemorrhage in neonatal asphyxia (OR=0.304, 0.085). Conclusion: The incidence of
retinal hemorrhage in neonatal asphyxia was 28.29%. The degree of neonatal
asphyxia and delivery mode may play roles in the occurrence of retinal hemorrhage
in newborns with asphyxia. With aggravation of asphyxia, the degree of retinal
hemorrhage may increase. (Chin J Ophthalmol, 2017, 53: 358-362).
PMID- 28494565
TI - [The protection of hydrogen-rich saline on a rat dry eye model induced by
scopolamine hydrobromide].
AB - Objective: To evaluate the effect of hydrogen-rich saline (HRS) on dry eye rats
induced by subcutaneous injection of scopolamine hydrobromide. Methods:
Experiment research. Thirty female Wistar rats at about six weeks old were
randomly divided into the normal group, dry eye group, HRS eyedrops group, normal
saline eyedrops group (NS), HRS intraperitoneal injection group and NS
intraperitoneal injection group, with 5 rats in each group. The dry eye was
induced by subcutaneous injection of scopolamine hydrobromide in the latter five
groups. The clinical signs of dry eye such as tear volume (SIt), tear break-up
time (BUT) and corneal epithelial fluorescein staining scores were evaluated on
day 7, 14, 21 and 28. On the 28th day, ten eyes in each group were enucleated and
processed for paraffin sections for HE, PAS and immunohistochemistry stainings.
Analysis of variance was used to test the data, and independent samples t-test
was used for comparison between the two groups. Two-way repeated measure ANOVA
was used to compare the difference among groups at different time points, one-way
ANOVA was used to test the comparisons of the clinical signs at one time, and LSD
was used to for comparison between two groups. Results: Before and after the
experiment of the day 7, 14, 21, 28, the values of SIt in HRS eyedrops group and
HRS intraperitoneal injection group were respectively:(3.625+/-1.157),(3.313+/
0.704),(3.250+/-0.535),(3.313+/-0.372), (3.375+/-0.582)mm and (3.500+/-1.019),
(2.893+/-0.656), (3.321+/-0.668), (3.179+/-0.575), (3.214+/-0.871)mm. The values
of BUT were respectively: (2.750+/-0.707), (2.688+/-0.594), (2.813+/-0.753),
(3.000+/-0.756), (2.750+/-0.707)s and (3.000+/-0.679), (2.321+/-0.464), (2.750+/
0.753), (3.214+/-0.699), (2.679+/-0.608)s. The values of fluorescein staining
score were respectively: (6.250+/-0.707), (8.875+/-0.641), (8.750+/-0.707),
(9.250+/-0.463), (8.250+/-1.282) and (6.000+/-0.679), (9.143+/-1.027), (8.857+/
0.770), (9.143+/-0.949), (8.500+/-0.760). The difference of SIt, BUT and
fluorescein staining score between the groups was statistically significant on
the 14th day(F=5.194, 3.894, 16.487, P<0.05), the values of SIt, BUT and
fluorescein staining score of HRS eyedrops group showed significantly better than
NS eyedrops group(P<0.05), HRS intraperitoneal injection group showed
significantly better than NS intraperitoneal injection group(P<0.05), and there
was no significant difference between HRS eyedrops group and HRS intraperitoneal
injection group(P>0.05), which remained stable until the day 28. On the 28(th)
day, HE, PAS and immunohistochemistry stainings showed the corneal and
conjunctival epithelia became smooth and regular, the cell layer number
decreased, the tissue hyperplasia and edema were lightened, and the size of
goblet cells tended to be normal, and the squamous metaplasia and inflammation
were relieved. In HRS eyedrops group and HRS intraperitoneal injection group.
Conclusions: HRS eyedrops group and HRS intraperitoneal injection group can
relieve the signs of dry eye, improve the pathological damage of cornea and
conjunctiva, and protect the ocular surface of a rat dry eye model, which is
better than NS groups from the 14(th) day. (Chin J Ophthalmol, 2017, 53: 363
372).
PMID- 28494567
TI - [The advances in research on precisely inducing retinal ganglion cells from stem
cells].
AB - The injury and repair of retinal neurons is a common scientific problem in the
occurrence, development and prognosis of neuronal visual impairment. Transplant
of retinal ganglion cells (RGCs) differentiated from stem cells opens a new
avenue for treatment of glaucoma and optic neuronal degenerative diseases. For
the goal to explore the optimal method for RGCs replacement, this review
summarizes the current information regarding the classification and application
of stem cells, the growth characteristics of RGCs and the precise methods to
induce RGCs, and discusses some important issues that need resolving and are
related to RGCs transplantation. It is hoped that this article will provide
useful theoretical basis for the research of this field. (Chin J Ophthalmol,
2017, 53: 381-385).
PMID- 28494566
TI - [The prevalence of blindness caused by primary angle closure glaucoma in middle
aged Chinese population: a systematic review and meta-analysis].
AB - Objective: To evaluate the rate of blindness caused by primary angle closure
glaucoma (PACG) in Chinese population of more than 40 years old, and to explore
the effectiveness of a prevention and treatment system on PACG. Methods: We
searched the databases of Pubmed, ScienceDirect, Springer Link, CNKI and Wanfang
Data and collected all the original studies of the prevalence and blindness of
angle closure glaucoma in China. The population was limited to over 40 years old.
The research site was limited to the community-based, while the published time
was not limited. Two researchers completed the literature search, data extraction
and methodological quality assessment independently, with same criteria. Meta
analysis was performed using R software. Results: Five papers were included in
this study finally. A total of 26 437 cases of natural population over the age of
40 were observed, and 306 cases of angle closure glaucoma were found, of which
113 cases had binocular or monocular blindness caused by PACG. The random effect
model meta-analysis results showed that the overall blindness rate was 38.3%
[95%CI (28.1%, 49.6%)]. In Beijing, where the prevention and treatment system was
well established, the blindness rate was far lower than that in the areas where
the system was poorly established. Compared with the past, the blindness rate
caused by PACG in Beijing decreased sharply. Conclusions: The rate of blindness
caused by PACG is still high in the mainland of China. The prevention and
treatment system is effective and worth promoting. (Chin J Ophthalmol, 2017, 53:
373-377).
PMID- 28494568
TI - [The research advances and applications of genome editing in hereditary eye
diseases].
AB - Genome editing is a cutting-edge technology that generates DNA double strand
breaks at the specific genomic DNA sequence through nuclease recognition and
cleavage, and then achieves insertion, replacement, or deletion of the target
gene via endogenous DNA repair mechanisms, such as non-homologous end joining,
homology directed repair, and homologous recombination. So far, more than 600
human hereditary eye diseases and systemic hereditary diseases with ocular
phenotypes have been found. However, most of these diseases are of incompletely
elucidated pathogenesis and without effective therapies. Genome editing
technology can precisely target and alter the genomes of animals, establish
animal models of the hereditary diseases, and elucidate the relationship between
the target gene and the disease phenotype, thereby providing a powerful approach
to studying the pathogenic mechanisms underlying the hereditary eye diseases. In
addition, correction of gene mutations by the genome editing brings a new hope to
gene therapy for the hereditary eye diseases. This review introduces the
molecular characteristics of 4 major enzymes used in the genome editing,
including homing endonucleases, zinc finger nucleases, transcription activator
like effector nucleases, and clustered regularly interspaced short palindromic
repeats (CRISPR)/ CRISPR-associated protein 9 (Cas9), and summarizes the current
applications of this technology in investigating the pathogenic mechanisms
underlying the hereditary eye diseases. (Chin J Ophthalmol, 2017, 53: 386-371).
PMID- 28494569
TI - [Research advances on cortical functional and structural deficits of amblyopia].
AB - Previous studies have observed functional deficits in primary visual cortex. With
the development of functional magnetic resonance imaging and electrophysiological
technique, the research of the striate, extra-striate cortex and higher-order
cortical deficit underlying amblyopia reaches a new stage. The neural mechanisms
of amblyopia show that anomalous responses exist throughout the visual processing
hierarchy, including the functional and structural abnormalities. This review
aims to summarize the current knowledge about structural and functional deficits
of brain regions associated with amblyopia. (Chin J Ophthalmol, 2017, 53: 392
395).
PMID- 28494570
TI - Investigation of Bulk Traps by Conductance Method in the Deep Depletion Region of
the Al2O3/GaN MOS Device.
AB - Conductance method was employed to study the physics of traps (e.g., interface
and bulk traps) in the Al2O3/GaN MOS devices. By featuring only one single peak
in the parallel conductance (G p/omega) characteristics in the deep depletion
region, one single-level bulk trap (E C-0.53 eV) uniformly distributed in GaN
buffer was identified. While in the subthreshold region, the interface traps with
continuous energy of E C-0.4~0.57 eV and density of 0.6~1.6 * 1012 cm-2 were
extracted from the commonly observed multiple G p/omega peaks. This methodology
can be used to investigate the traps in GaN buffer and facilitates making the
distinction between bulk and interface traps.
PMID- 28494571
TI - Synthesis of n-type Mg2Si/CNT Thermoelectric Nanofibers.
AB - Magnesium silicide (Mg2Si)/carbon nanotube (CNT) thermoelectric nanofibers for
use as a flexible thermoelectric material were successfully synthesized through
the combined processes of the sol-gel method, magnesiothermic reduction, and
liquid-solid phase reaction. In the resulting product, each CNT was coated with
Mg2Si which was an approximately 60-nm-thick single crystal. The synthesized
Mg2Si-coated CNTs exhibited n-type thermoelectric behavior confirming that n-type
thermoelectric composite nanofibers were successfully obtained.
PMID- 28494572
TI - SERS Detection of Biomolecules by Highly Sensitive and Reproducible Raman
Enhancing Nanoparticle Array.
AB - This paper describes the preparation of nanoarrays composed of silver
nanoparticles (AgNPs: 20-50 nm) for use as surface-enhanced Raman scattering
(SERS) substrates. The AgNPs were grown on porous anodic aluminum oxide (AAO)
templates by electrochemical plating, and the inter-channel gap of AAO channels
is between 10 and 20 nm. The size and interparticle gap of silver particles were
adjusted in order to achieve optimal SERS signals and characterized by scanning
electron microscopy, atomic force microscopy, and Raman spectroscopy. The
fluctuation of SERS intensity is about 10-20% when measuring adenine solutions,
showing a great reproducible SERS sensing. The nanoparticle arrays offer a large
potential for practical applications as shown by the SERS-based quantitative
detection and differentiation of adenine (A), thymine (T), cytosine (C), guanine
(G), beta-carotene, and malachite green. The respective detection limits are <1
ppb for adenine and <0.63 ppm for beta-carotene and malachite green,
respectively. Uniform and reproducible Raman enhancement enabled by Ag
nanoparticle array embedded in anodic aluminum oxide differentiates and helps
quantify DNA canonical nucleobases (adenine, thymine, cytosine, and guanine).
PMID- 28494573
TI - Hysteresis of Low-Temperature Thermal Conductivity and Boson Peak in Glassy (g)
As2S3: Nanocluster Contribution.
AB - Experimental results of the thermal conductivity (k(T)) of nanostructured g-As2S3
during cooling and heating processes within the temperature range from 2.5 to 100
K have been analysed. The paper has considered thermal conductivity is weakly
temperature k(T) dependent from 2.5 to 100 K showing a plateau in region from 3.6
to 10.7 K during both cooling and heating regimes. This paper is the first
attempt to consider the k(T) hysteresis above plateau while heating in the range
of temperature from 11 to 60 K. The results obtained have not been reported yet
in the scientific literature. Differential curve Deltak(T) of k(T) (heating k(T)
curve minus cooling k(T) curve) possesses a complex asymmetric peak in the energy
range from 1 to 10 meV. Deltak(T) reproduces the density of states in a
g(omega)/omega 2 representation estimated from a boson peak experimentally
obtained by Raman measurement within the range of low and room temperatures.
Theoretical and experimental spectroscopic studies have confirmed a glassy
structure of g-As2S3 in cluster approximation. The origin of the low-frequency
excitations resulted from a rich variety of vibrational properties. The
nanocluster vibrations can be created by disorder on atomic scale.
PMID- 28494574
TI - Endoscopic Management of Peri-Pancreatic Fluid Collections.
AB - In the past decade, there has been a progressive paradigm shift in the management
of peri-pancreatic fluid collections after acute pancreatitis. Refinements in the
definitions of fluid collections from the updated Atlanta classification have
enabled better communication amongst physicians in an effort to formulate optimal
treatments. Endoscopic ultrasound (EUS)-guided drainage of pancreatic pseudocysts
has emerged as the procedure of choice over surgical cystogastrostomy. The
approach provides similar success rates with low complications and better quality
of life compared with surgery. However, an endoscopic "step up" approach in the
management of pancreatic walled-off necrosis has also been advocated. Both
endoscopic and percutaneous drainage routes may be used depending on the
anatomical location of the collections. New-generation large diameter EUS
specific stent systems have also recently been described. The device allows
precise and effective drainage of the collections and permits endoscopic
necrosectomy through the stents.
PMID- 28494575
TI - Combination Therapy for Chronic Hepatitis B: Current Updates and Perspectives.
AB - Nucleos(t)ide analogues (NUCs) and interferon have been used for several decades
to treat chronic hepatitis B; however, the therapeutic response remains
unsatisfactory. Although NUC therapy exhibits potent on-treatment viral
suppression, frequent off-therapy virological relapses suggest an indefinite
treatment course. Interferon modulates the innate and adaptive antiviral immune
responses and thus increases the chance of viral eradication. Interferon therapy
has the advantage of a finite duration, absence of drug resistance, and durable
posttreatment responses. Therefore, the combination of NUCs and interferon can
theoretically facilitate a synergistic therapeutic effect. This paper summarizes
the current strategies of various combination therapies into three categories:
the simultaneous "dual" strategy, sequential combination "add-on" strategy, and
"switch" strategy. Generally, dual therapy exhibits greater on-treatment and off
therapy viral suppression and lower drug resistance compared with NUC
monotherapy. Compared with interferon monotherapy, dual therapy has greater on
treatment viral suppression but shows no difference in off-therapy sustained
virological responses. Specific add-on or switch strategies provide promising on
treatment efficacy in select patients. Pretreatment or on-treatment quantitative
hepatitis B surface antigen and e antigen are predictive for the treatment
efficacy of combination therapy. The optimal schedule of combination regimens and
individualized therapy remain to be comprehensively evaluated.
PMID- 28494576
TI - Diverticular Disease: An Update on Pathogenesis and Management.
AB - Diverticular disease is one of the most common conditions in the Western world
and one of the most common findings identified at colonoscopy. Recently, there
has been a significant paradigm shift in our understanding of diverticular
disease and its management. The pathogenesis of diverticular disease is thought
to be multifactorial and include both environmental and genetic factors in
addition to the historically accepted etiology of dietary fiber deficiency.
Symptomatic uncomplicated diverticular disease (SUDD) is currently considered a
type of chronic diverticulosis that is perhaps akin to irritable bowel syndrome.
Mesalamine, rifaximin and probiotics may achieve symptomatic relief in some
patients with SUDD, although their role(s) in preventing complications remain
unclear. Antibiotic use for acute diverticulitis and elective prophylactic
resection surgery are considered more individualized treatment modalities that
take into account the clinical status, comorbidities and lifestyle of the
patient. Our understanding of the pathogenesis of diverticular disease continues
to evolve and is likely to be diverse and multifactorial. Paradigm shifts in
several areas of the pathogenesis and management of diverticular disease are
explored in this review.
PMID- 28494578
TI - Early and late ureteral complications after renal transplant.
AB - BACKGROUND: Ureteral strictures occur in approximately 3-8% of kidney transplant
(KTx) recipients. They are usually a late event which needs surgical re
intervention with a subsequent increased risk of graft loss. This retrospective
study presents a single-centre experience in managing ureteral complications
using firstly a minimally invasive approach. METHODS: Between January 2000 and
November 2012, 838 patients underwent KTx with Lich-Gregoire uretero-vesical
anastomosis. Ureteral complications consisting in 6 fistulas and 18 strictures
were observed in 24 grafts, with an overall incidence of 2.6%. The retrograde
placement of a double J stent was attempted first in 16 grafts and succeeded in
12 (75%); the remaining 4 cases underwent open repair with anastomosis to the
native ureter. Antegrade/combined ureteral stenting via a percutaneous
nephrostomy was attempted in 8 grafts and succeeded in 4 (50%); the remaining 4
(2 fistulas and 2 strictures) underwent open repair with anastomosis to the
native ureter. RESULTS: After an average period of 8.36 months (range 1-36) the
double J stents were removed and the ureters were unobstructed in 11 (45.8%),
while open surgical treatment was necessary in the remaining 5. Repeated
cystoscopic stent changes were successfully performed in 13 patients. Early onset
ureteral stenoses were found in 10 out of 19 patients and successfully treated by
a mini-invasive approach in 50% of the cases. Three renal grafts were lost, but
this was not due to ureteral complications. CONCLUSIONS: Minimally invasive
procedures are recommended in early complications, although open reconstructive
surgery maintains a role in late severe obstructions after KTx.
PMID- 28494577
TI - Sessile Serrated Adenomas: How to Detect, Characterize and Resect.
AB - Serrated polyps are important contributors to the burden of colorectal cancers
(CRC). These lesions were once considered to have no malignant potential, but
currently up to 30% of all CRC are recognized to arise from the serrated
neoplasia pathway. The primary premalignant lesions are sessile serrated
adenomas/polyps (SSA/Ps), although traditional serrated adenomas are relatively
uncommon. Compared to conventional adenomas, SSA/Ps are morphologically subtle
with indistinct borders, may be difficult to detect endoscopically, are more
prevalent than previously thought, are associated with synchronous and
metachronous advanced neoplasia, and have a higher risk of incomplete resection.
Although many lesions remain "dormant," progressive disease is associated with
the development of dysplasia and more rapid progression to CRC. As a result,
SSA/Ps are strongly implicated in the development of interval cancers. These
factors represent unique challenges that require a meticulous approach to their
management. In this review, we summarize the contemporary literature on the
characterization, detection and resection of SSA/Ps.
PMID- 28494579
TI - Multiparametric prostate MRI: technical conduct, standardized report and clinical
use.
AB - Multiparametric prostate MRI (mp-MRI) is an emerging imaging modality for
diagnosis, characterization, staging, and treatment planning of prostate cancer
(PCa). The technique, results reporting, and its role in clinical practice have
been the subject of significant development over the last decade. Although mp-MRI
is not yet routinely used in the diagnostic pathway, almost all urological
guidelines have emphasized the potential role of mp-MRI in several aspects of PCa
management. Moreover, new MRI sequences and scanning techniques are currently
under evaluation to improve the diagnostic accuracy of mp-MRI. This review
presents an overview of mp-MRI, summarizing the technical applications, the
standardized reporting systems used, and their current roles in various stages of
PCa management. Finally, this critical review also reports the main limitations
and future perspectives of the technique.
PMID- 28494580
TI - Access to Chiral Silicon Centers for Application to Circularly Polarized
Luminescence Materials.
AB - Asymmetric arylation of secondary silanes catalyzed by a Pd-chiral
phosphoramidite complex was developed for application to low-molecular-weight
circularly polarized luminescence (CPL) materials. The asymmetric arylation
provided a convenient, efficient synthetic method for a variety of chiral
tertiary silanes (2-21), which were key intermediates for preparing the
quaternary silicon center. A stepwise, one-pot procedure was used to transform
the appropriate aryl iodide to the quaternary silane (22) with good yield and
enantioselectivity. Among compounds synthesized in this work, four optically pure
tertiary silanes (18-21) were selected to investigate the relationship between
the structure and optical properties. Optically pure (S,S)-21 displayed the
highest CPL emission with a high fluorescence quantum yield (glum: +0.008, PhiF:
0.42). This simple molecular design provides new strategies for developing small
organic CPL dyes.
PMID- 28494581
TI - Synthesis of 5-Amino and 3,5-Diamino Substituted 1,2,4-Thiadiazoles by I2
Mediated Oxidative N-S Bond Formation.
AB - An oxidative N-S bond formation reaction has been established for 1,2,4
thiadiazole synthesis employing molecular iodine as the sole oxidant. The
features of the present reaction include no use of transition metals, mild
reaction conditions, simple operation, and short reaction time. This versatile
synthetic approach is broadly applicable to a variety of imidoyl and guanyl
thiourea substrates to produce 5-amino and 3,5-diamino substituted 1,2,4
thiadiazole derivatives, respectively, in an efficient and scalable fashion.
PMID- 28494583
TI - Isolation, Identification, and Biological Evaluation of Phenolic Compounds from a
Traditional North American Confectionery, Maple Sugar.
AB - Maple sap, collected from the sugar maple (Acer saccharum) tree, is boiled to
produce the popular plant-derived sweetener, maple syrup, which can then be
further evaporated to yield a traditional North American confectionery, maple
sugar. Although maple sap and maple syrup have been previously studied, the
phytochemical constituents of maple sugar are unknown. Herein, 30 phenolic
compounds, 1-30, primarily lignans, were isolated and identified (by HRESIMS and
NMR) from maple sugar. The isolates included the phenylpropanoid-based lignan
tetramers (erythro,erythro)-4",4'''-dihydroxy-3,3',3",3''',5,5'-hexamethoxy
7,9';7',9-diepoxy-4,8";4',8'''-bisoxy-8,8'-dineolignan-7",7''',9",9'''-tetraol,
29, and (threo,erythro)-4",4'''-dihydroxy-3,3',3",3''',5,5'-hexamethoxy-7,9';7',9
diepoxy-4,8";4',8'''-bisoxy-8,8'-dineolignan-7",7''',9",9'''-tetraol, 30, neither
of which have been identified from maple sap or maple syrup before. Twenty of the
isolates (selected on the basis of sample quantity available) were evaluated for
their potential biological effects against lipopolysaccharide-induced
inflammation in BV-2 microglia in vitro and juglone-induced oxidative stress in
Caenorhabditis elegans in vivo. The current study increases scientific knowledge
of possible bioactive compounds present in maple-derived foods including maple
sugar.
PMID- 28494582
TI - Highly Oxygenated Grayanane Diterpenoids from Flowers of Pieris japonica and
Structure-Activity Relationships of Antifeedant Activity against Pieris
brassicae.
AB - Six new highly oxygenated grayanane diterpenoids, neopierisoids G-L, 1-6,
together with 10 known related compounds, 7-16, were identified from the flowers
of the poisonous plant Pieris japonica. The structures were elucidated on the
basis of comprehensive NMR spectroscopy and mass analysis. The relative
configurations of 1-6 were elucidated by analysis of ROESY spectra and comparison
of NMR data with the analogues. The absolute configurations of 1-6 were
established by the X-ray diffraction analysis of 1 and comparison of the CD
spectra of 1-6. Compared with the skeleton of the normal grayanane diterpenoids,
compounds 1-6 shared an unusual seco A ring moiety. The antifeedant activities of
compounds 1-16 against Pieris brassicae were evaluated by using a dual-choice
bioassay, and compounds 1-10 with a normal grayanane skeleton showed potent
antifeedant activity against P. brassicae. The structure-activity relationships
of antifeedant activities of 1-16 against P. brassicae are discussed.
PMID- 28494584
TI - Development of a Common Procedure for the Determination of Methylmercury,
Ethylmercury, and Inorganic Mercury in Human Whole Blood, Hair, and Urine by
Triple Spike Species-Specific Isotope Dilution Mass Spectrometry.
AB - We report the first common methodology for the simultaneous determination of
methylmercury (MeHg), ethylmercury (EtHg), and inorganic mercury (Hg(II)) in
human blood hair and urine. With the exception of the initial sample mass (0.15 g
for blood, 0.5 g for urine, and 0.1 g for hair), the same sample preparation and
gas chromatography-inductively coupled plasma mass spectrometry (GC-ICPMS)
measurement conditions are employed for the three matrixes providing experimental
values in agreement with the certified values in the analysis of NIST SRM 955c
(Caprine Blood) Level 3 and the certified human hairs IAEA 085 and IAEA 086.
Also, the method provides quantitative recoveries for the three Hg species in the
analysis of fortified human urine samples at 1, 2, and 5 ng Hg g-1. Mercury
species concentrations for levels 2 and 4 of SRM 955c are reported here for the
first time. A systematic interconversion of EtHg into Hg(II) was obtained for all
matrixes reaching values up to 95% in blood, 29% in hair, and 11% in urine. MeHg
dealkylation was also observed in a lesser extent in blood and hair analyses, but
it was not observed when analyzing urine samples. Hg methylation was not observed
in any matrix. The amount of NaBPr4 added for derivatization has been found to be
the main factor responsible for Hg species interconversion. This work
demonstrates for the first time that experimental conditions optimized for SRM
955c (caprine blood) are not valid for human blood samples as the optimum initial
sample amount for a real sample is more than 3 times lower than that for SRM
955c.
PMID- 28494585
TI - Induced Fit Is a Special Case of Conformational Selection.
AB - Conformational selection (CS) and induced fit (IF) are two widely used
interpretations of binding of a ligand to biological macromolecules. Both
mechanisms envision a two-step reaction in which a conformational transition
either precedes (CS) or follows (IF) the binding step. Under pseudo-first-order
conditions where the ligand is in excess compared to the macromolecule, both
mechanisms produce two relaxations. A fast one eventually increases linearly with
ligand concentration and reflects the binding interaction. A slow one saturates
to a constant value after decreasing or increasing hyperbolically with ligand
concentration. This relaxation is the one most often accessible to experimental
measurements and is potentially diagnostic of the mechanism involved. A
relaxation that decreases unequivocally identifies CS, but a hyperbolic increase
is compatible with both CS and IF. The potential ambiguity between the two
mechanisms is more than qualitative. Here we show that the entire kinetic
repertoire of IF is nothing but a mathematical special case of CS as revealed by
a simple transformation of the rate constants, which emphasizes the need for
independent support of either mechanism from additional experimental evidence. We
discuss a simple strategy for distinguishing between IF and CS under the most
common conditions encountered in practice, i.e., when the ligand is in excess
compared to the macromolecule and a single relaxation is accessible to
experimental measurements.
PMID- 28494586
TI - Thermodynamic Study of the Interaction of Bovine Serum Albumin and Amino Acids
with Cellulose Nanocrystals.
AB - The interaction of bovine serum albumin (BSA) with sulfated, carboxylated, and
pyridinium-grafted cellulose nanocrystals (CNCs) was studied as a function of the
degree of substitution by determining the adsorption isotherm and by directly
measuring the thermodynamics of interaction. The adsorption of BSA onto
positively charged pyridinium-grafted cellulose nanocrystals followed Langmuirian
adsorption with the maximum amount of adsorbed protein increasing linearly with
increasing degree of substitution. The binding mechanism between the positively
charged pyridinum-grafted cellulose nanocrystals and BSA was found to be
endothermic and based on charge neutralization. A positive entropy of adsorption
associated with an increase of the degree of disorder upon addition of BSA
compensated for the unfavorable endothermic enthalpy and enabled formation of
pyridinium-g-CNC-BSA complexes. The endothermic enthalpy of adsorption was
further found to decrease as a function of increasing degree of substitution.
Negatively charged cellulose nanocrystals bearing sulfate and/or carboxylic
functionalities were found to not interact significantly with the BSA protein. To
investigate in more detail the role of single amino acids in the adsorption of
proteins onto cellulose nanocrystals, we also studied the interaction of
different types of amino acids with CNCs, i.e., charged (lysine, aspartic acid),
aromatic (tryptophan, tyrosine), and polar (serine) amino acids. We found that
none of the single amino acids bound with CNCs irrespective of surface charge and
that therefore the binding of proteins with CNCs appears to require larger amino
acid sequences that induce a greater entropic contribution to stabilize binding.
Single amino acids are thus not adsorbed onto cellulose nanocrystals.
PMID- 28494587
TI - Fabrication and Electrochemical Performance of Structured Mesoscale Open Shell
V2O5 Networks.
AB - Crystalline vanadium pentoxide (V2O5) has attracted significant interest as a
potential cathode material for energy storage applications due to its high
theoretical capacity. Unfortunately, the material suffers from low conductivity
as well as slow lithium ion diffusion, both of which affect how fast the
electrode can be charged/discharged and how many times it can be cycled.
Colloidal crystal templating (CCT) provides a simple approach to create well
organized 3-D nanostructures of materials, resulting in a significant increase in
surface area that can lead to marked improvements in electrochemical performance.
Here, a single layer of open shell V2O5 architectures ca. 1 MUm in height with
ca. 100 nm wall thickness was fabricated using CCT, and the electrochemical
properties of these assemblies were evaluated. A decrease in polarization
effects, resulting from the higher surface area mesostructured features, was
found to produce significantly enhanced electrochemical performance. The
discharge capacity of an unpatterned thin film of V2O5 (~8.1 MUAh/cm2) was found
to increase to ~10.2 MUAh/cm2 when the material was patterned by CCT, affording
enhanced charge storage capabilities as well as a decrease in the irreversible
degradation during charge-discharge cycling. This work demonstrates the
importance of creating mesoscale electrode surfaces for improving the performance
of energy storage devices and provides fundamental understanding of the means to
improve device performance.
PMID- 28494588
TI - Cyclization of Methyl-Coumalate-Derived Methyl 1-Benzamido-6-oxo-1,6
dihydropyridine-3-carboxylates: Assembly of the [1,2,4]Triazolo[1,5-a]pyridine
Ring System.
AB - An efficient three-step synthesis of a series of fused bicyclic s
[1,2,4]triazolo[1,5-a]pyridines 1 was accomplished utilizing novel intermediates
derived from inexpensive, commercially available hydrazides A and methyl
coumalate B. A significant feature of this approach was the formation of a
dihydrazide intermediate 2, bypassing the need for oxidative N-N bond formation
in the 1,2,4-triazole synthesis. Further purification of the dihydrazides 2,
beyond simple isolation, proved to be unnecessary owing to the impurity rejection
afforded by the crystalline oxadiazolium salts 3. Additionally, the prepared
oxadiazolium perchlorate salts showed excellent moisture stability, an unusual
feature in compounds of this type.
PMID- 28494589
TI - Complexes Covered with Phosphorylcholine Groups Prepared by Mixing Anionic
Diblock Copolymers and Cationic Surfactants.
AB - Anionic diblock copolymers (PmAn) composed of biocompatible polybetaine, poly(2
(methacryloyloxy)ethyl phosphorylcholine) (PMPC), and anionic poly(sodium 2
(acrylamido)-2-methylpropanesulfonate) (PAMPS) were synthesized via reversible
addition-fragmentation chain transfer (RAFT) radical polymerization. Two types of
diblock copolymers (P24A217 and P100A99) were prepared with different
compositions. The PmAn/CTAB complexes were formed by a stoichiometrically charge
neutralized mixture of anionic PmAn and cationic cetyltrimethylammonium bromide
(CTAB) micelles in water. The complexes prepared using P24A217 and P100A99 were
vesicles and micelles, respectively, and were covered with hydrophilic PMPC
shells. The complexes dissociated upon addition of NaCl because the complex was
maintained through electrostatic interactions. The P24A217/CTAB vesicles could
encapsulate uncharged hydrophilic guest molecules into the interior of the
aqueous phase.
PMID- 28494590
TI - Linking Silica Support Morphology to the Dynamics of Aminopolymers in Composites.
AB - A combined computational and experimental approach is used to elucidate the
effect of silica support morphology on polymer dynamics and CO2 adsorption
capacities in aminopolymer/silica composites. Simulations are based on coarse
grained molecular dynamics simulations of aminopolymer composites where a
branched aminopolymer, representing poly(ethylenimine) (PEI), is impregnated into
different silica mesoporous supports. The morphology of the mesoporous supports
varies from hexagonally packed cylindrical pores representing SBA-15, double
gyroids representing KIT-6 and MCM-48, and cagelike structures representing SBA
16. In parallel, composites of PEI and the silica supports SBA-15, KIT-6, MCM-48,
and SBA-16 are synthesized and characterized, including measuring their CO2
uptake. Simulations predict that a 3D pore morphology, such as those of KIT-6,
MCM-48, and SBA-16, will have faster segmental mobility and have lower
probability of primary amine and surface silanol associations, which should
translate to higher CO2 uptake in comparison to a 2D pore morphology such as that
of SBA-15. Indeed, it is found that KIT-6 has higher CO2 uptake than SBA-15 at
equivalent PEI loading, even though both supports have similar surface area and
pore volume. However, this is not the case for the MCM-48 support, which has
smaller pores, and SBA-16, whose pore structure rapidly degrades after PEI
impregnation.
PMID- 28494591
TI - In Situ Multimodal 3D Chemical Imaging of a Hierarchically Structured Core@Shell
Catalyst.
AB - A Cu/ZnO/Al2O3@ZSM-5 core@shell catalyst active for one-step conversion of
synthesis gas to dimethyl ether (DME) was imaged simultaneously and in situ using
synchrotron-based micro X-ray fluorescence (MU-XRF), X-ray diffraction (MU-XRD),
and scanning transmission X-ray microscopy (STXM) computed tomography (CT) with
micrometer spatial resolution. An identical sample volume was imaged stepwise,
first under oxidizing and reducing atmospheres (imitating calcination and
activation processes), and then under model reaction conditions for DME synthesis
(H2:CO:CO2 ratio of 16:8:1, up to 250 degrees C). The multimodal imaging methods
offered insights into the active metal structure and speciation within the
catalyst, and allowed imaging of both the catalyst core and zeolite shell in a
single acquisition. Dispersion of nanosized Cu species was observed in the
catalyst core during reduction, with formation of a metastable Cu+ phase at the
core-shell interface. Under DME reaction conditions at 1 bar, the coexistence of
Cu0 in the active catalyst core together with partially oxidized Cu species was
unraveled. The zeolite shell and core-shell interface remained stable under all
conditions, preserving the bifunctional nature of the catalyst. These
observations are inaccessible using standard bulk techniques like X-ray
absorption spectroscopy (XAS) and XRD, demonstrating the potential of multimodal
in situ X-ray CT for characterization of hierarchically designed materials, which
stand to benefit tremendously from such 3D spatially resolved measurements.
PMID- 28494592
TI - ACS Infectious Diseases Special Issue Focused on Drug Discovery for Global
Health.
PMID- 28494593
TI - Laser irradiation of Mg-Al-Zn alloy: Reduced electrochemical kinetics and
enhanced performance in simulated body fluid.
AB - As a lightweight metal with mechanical properties similar to natural bone, Mg and
its alloys are great prospects for biodegradable, load bearing implants. However,
rapid degradation and H2 gas production in physiological media has prevented
widespread use of Mg alloys. Surface heterogeneities in the form of intermetallic
particles dominate the corrosion response. This research shows that surface
homogenization significantly improved the biological corrosion response observed
during immersion in simulated body fluid (SBF). The laser processed Mg alloy
exhibited a 50% reduction in mass loss and H2 evolution after 24 h of immersion
in SBF when compared to the wrought, cast alloy. The laser processed samples
exhibited increased wettability as evident from wetting angle studies, further
suggesting improved biocompatibility. Electrochemical analysis by potentiodynamic
polarization measurements showed that the anodic and cathodic kinetics were
reduced following laser processing and are attributed to the surface chemical
homogeneity.
PMID- 28494594
TI - Caring for baby's teeth starts before birth.
AB - Care for a child's teeth and gums can start even before the baby is born.
Pregnancy causes many hormonal changes, among these the rise of estrogen and
progesterone increases the risk of developing oral health problems, like
gingivitis and periodontitis.The presence of maternal periodontal diseases and
active infections has been associated with adverse pregnancy outcomes, such as
preterm birth, preeclampsia, gestational diabetes and foetal loss. Therefore, it
is important to educate pregnant women about their oral hygiene and the
importance of taking care of their newborn's oral health. J. Courtad and A.
Horowitz devised six steps to help us in promoting oral health (ADA Convention-
2016 Denver): 1. Asking right questions such as "Has there been any change in
your health history since your last visit?" and "When did you brush your teeth
last?" is recommended in order to find out wether your patient is pregnant and to
get to know her dental care better. 2. Know your audience: Mothers are
increasingly informed about childbearing, however not every piece of information
is correct! Let them know what they are doing well and do not sound like you are
preaching to them. 3. Use informal language. 4. Emphasize the need to get dental
treatments and to prevent decay: Parents can pass bacteria to their newborns,
therefore we want mothers to have a healthy mouth before they give birth! 5. Mom
and dad as first dentists: Teach parents about nutrition and when and how to
clean their children's mouth. 6. Listen to patients and confirm what they heard:
Ask the patient to tell you what she is going to do at home and confirm. As
pregnant women are more receptive to oral health information than in any other
moment in their life, our aim is to take this opportunity by providing good
prevention information and instilling healthy habits as early as possible.
PMID- 28494595
TI - Clinical performance of a glass ionomer sealant protected with two different
resin-based agents over a 2-year follow-up period.
AB - AIM: To evaluate the effects of two different resin coating materials on the
clinical performance of a conventional glass ionomer sealant. MATERIALS AND
METHODS: Permanent first mandibular molars of 60 children aged 6-9 years were
sealed with Fuji VII. In each child, G-Coat Plus coating agent was applied to
molars on one side and Heliobond coating agent to molars on the opposite side of
the mouth. Clinical evaluations were carried out at 1, 6, 12, 18 and 24 months
after sealant and coating application. RESULTS: At 1, 6, 12, 18 and 24 months
after sealant and coating application, total sealant retention rates were 88%,
40%, 19%, 15% and 9% for molars coated with G-Coat Plus, and 93%, 47%, 17%, 15%
and 7% for those coated with Heliobond. The differences between the two coating
agents were not statistically significant (p>0.05). No incidence of caries was
observed in either group during the two-year evaluation period. STATISTICS:
Wilcoxon signed rank test was used to compare differences in retention rates and
caries incidence by coating agent. CONCLUSION: Although retention rates of Fuji
VII were relatively low and similar for both resin coating agents tested, dental
caries were not observed in either group during the 24-month study period. In
children with a high risk of caries and partially erupted molars, the use of a
glass ionomer sealant with a resin-based coating agent should be encouraged.
PMID- 28494596
TI - Dental caries, parents educational level, family income and dental service
attendance among children in Italy.
AB - AIM: The aim of this study was to verify whether socioeconomic determinants, such
as parents' educational level, family income and dental service attendance by
children, are associated with the presence of caries among an Italian population
of children. MATERIALS AND METHODS: An observational retrospective study was
carried out in a population of children aged 4-14 years who visited the
Paediatric Dentistry Department of the University of Perugia, Italy. Children
were stratified according to familial socioeconomic level (father's and mother's
educational level, family income) and dental service attendance of children. Age-
and sex- adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs) were
calculated by means of multivariate logistic regression models. RESULTS: A sample
of 231 children (mean age 8.1 yrs, SD 2.6; 127 males, 104 females) was recruited.
One hundred and sixty three (70.46%) children in the study had caries. Caries
presence in children was higher in children where the mothers' educational level
was lower (OR =6.1; 95% CI = 3.1 to 12.7), in children where the fathers'
educational level was lower (OR =2.9; 95% CI =1.6 to 5.5) and in children with
lower family income (OR = 9.9; 95% 95% CI = 5.1 to 20.1). No statistically
significant difference were observed in terms of caries presence between the
children who were visited at least once by a dentist and children who were not
previously seen by a dental practitioner (OR = 0.8; 95% CI = 0.4 to 1.6).
CONCLUSION: Socioeconomic level was an important predictor of caries presence
among children. Both low income and low parental educational level were related
to an increased presence of caries, whereas previous dental visits experience did
not affect caries presence in children.
PMID- 28494597
TI - Surgical management of impacted primary teeth: report of two cases.
AB - AIM: Impaction of deciduous teeth is an uncommon event. The purpose of this
report is to describe two unusual eruption failures of a second primary molar and
their treatment management. CASE REPORT: The diagnostic and therapeutic protocol
of two cases selected at the Unit of Paediatric Dentistry, Department of Oral and
Maxillofacial Science, "Sapienza" University of Rome, Italy, are presented. In
both cases, the second deciduous molar was impacted, while no mechanical obstacle
like odontomas or supernumerary teeth were present. CONCLUSION: The two case
reports presented in this work are of scientific relevance, due to the rarity of
this type of pathology.
PMID- 28494598
TI - Dental trauma in Italian children and adolescents with special health care needs.
A cross-sectional retrospective study.
AB - AIM: Dental trauma is a frequent finding in people with special health care
needs. The aim of this study was to determine the prevalence of dental trauma in
a sample of Italian children and adolescents with special health care needs.
MATERIALS AND METHODS: 556 medical and dental records of children and adolescents
visited from January 2010 to March 2015 were examined. Information about medical
diagnosis, gender, site and type of dental trauma (DT) were collected. According
to age and reflecting the dentition stage, the sample was divided into 3 groups:
subjects aged 0-5 years (group A, primary dentition), 6-11 years (group B, mixed
dentition), 12-18 years (group C, permanent dentition). RESULTS: 113 individuals
experienced a DT (prevalence 20.3%), with no difference in relation to gender.
Individuals with cerebral palsy and autism showed the highest frequency of DT:
39.6% and 30.4%, respectively. The highest frequency of DT occurred both in group
A (21.8%) and B (21.5%), which differed significantly from group C (9%). Avulsion
was the most frequent type of DT in the primary dentition (24%) and enamel-dentin
fracture without pulp exposure in the permanent dentition (60%). Upper central
incisors were the most affected teeth. CONCLUSION: The prevalence of DT in a
sample of Italian children and adolescents with special health care needs is
high, especially in young individuals with cerebral palsy and autism. Preventive
strategies for those patients should be developed in order to reduce the risk of
DT.
PMID- 28494599
TI - A combined approach with passive and active repositioning of a traumatically
intruded immature permanent incisor.
AB - BACKGROUND: Severe damage to the tooth, periodontal ligament, and pulpal tissue
often occurs with intrusive luxation, and outcomes are quite unpredictable
because of the variable ways in which the injury may occur, which influences both
the choice of treatment and prognosis. CASE REPORT: This case presents a novel
method for the management of an intruded permanent maxillary central incisor with
an immature apex. At first, watchful waiting for spontaneous re-eruption was the
chosen treatment option. A palatal gingivectomy was performed and endodontic
access was established, following which, an intracanal medicament of calcium
hydroxide was applied. A root canal treatment was completed, and apexification
with mineral trioxide aggregate was performed. Re-eruption failed to reach
completion, so complete repositioning was performed with the aid of orthodontics
for two months. CONCLUSION: The present case illustrates the partial re-eruption
of a severely intruded immature permanent tooth with the use of interim
medication in the root canal. This case also shows complete re-eruption with the
aid of timely orthodontic repositioning after apexification.
PMID- 28494600
TI - Cephalometric changes after headgear anchored to the deciduous second molars in
the early mixed dentition.
AB - AIM: The present study aimed to evaluate the cephalometric effects of a headgear
anchored to the deciduous second molars in the early mixed dentition. MATERIALS
AND METHODS: Study design: The study followed a retrospective longitudinal design
and enrolled 31 consecutive patients (17 females and 14 males) treated with high
pull (HP) headgear anchored to the deciduous second molars, average age 8y 5m+/-
5m at pre-treatment time (T0) and 9y 8m+/- 6m at post-treatment time (T1). All
the patients wore the headgear for approximately 8-10 hours at night, with a
force of 250 g per side. The active phase of treatment ended once patients
obtained a distal step on permanent molars of at least 2 mm. Lateral cephalograms
at T0 and T1 were taken; 10 angular measurements were chosen as variables of the
study. The paired sample t-test was employed to assess the significance of the
differences of each variable between T0 and T1. RESULTS AND CONCLUSION: In this
group of Class II patients, HP headgear anchored to the deciduous second molars
in the early mixed dentition produced: significant reduction of SNA angle,
significant increase of SN/NL angle with no significant change in SN/ML angle,
significant labial flaring of upper incisors. As clinically evaluated, the
correction of the Class II occlusal relationship and the anterior crowding of
maxillary arch were also accomplished.
PMID- 28494601
TI - Relationship between oro and nasopharynx permeability and the direction of facial
growth.
AB - AIM: Most scientific literature relates vertical growth to individuals with
decreased upper airway permeability. However, we often find subjects with a long
face and a normal breathing pattern, most likely caused by other aetiological
factors. And, frequently, we also find decreased upper airway permeability with
horizontal growth. The aim of the study was to compare the cephalometric
measurements of the oro and nasopharynx permeability with the facial growth
direction and to identify the most common facial growth direction in individuals
with decreased upper airway permeability. MATERIALS AND METHODS: Cephalometric
analysis was carried out in 158 pre-adolescent patients at the Orthodontic
appointment, using facial profile teleradiographs. Parameters used were Jabarak's
ratio and measurement of oro-nasopharynx space. Data collected were submitted to
statistical treatment. RESULTS: This study points to the presence of an
intermediate growth in individuals with diminished oro and nasopharynx
permeability, either simultaneous or separate. The number of individuals with
diminished permeability and vertical growth is close to the number of individuals
with horizontal growth. CONCLUSIONS: The individuals with diminished permeability
of the upper airway present an intermediate growth direction, representing the
most frequent type. In the less common growth directions, there is a slight
tendency to horizontal facial growth verified in individuals with diminished
nasopharynx permeability. Also, a light tendency to vertical facial growth is
present when oropharynx permeability is reduced.
PMID- 28494602
TI - Are there any differences between first and second primary molar pulpectomy
prognoses? A retrospective clinical study.
AB - AIM: To determine if there are any significant differences between the prognoses
of pulpectomies done on first and second primary molars of the upper and lower
dental arch. MATERIALS AND METHODS: Study Design: The clinical study included 55
children who had undergone 86 pulpectomy treatments, 41 on the first molars and
45 on the second molars. The root canal filling material consisted of a paste
based on Walkhoff formula, containing Kri-1, calcium hydroxide and meta-cresol
formaldehyde. The same clinician carried out all pulpectomies. RESULTS: After the
analysis there were a total of 7 treatment failures (3 in the upper arch and 4 in
the lower). Four of the 7 failures were first primary molars and three were
second primary molars. STATISTICS: There were no significant differences in the
prognoses of the different kinds of primary molars. CONCLUSION: The anatomy of
the primary molars changes considerably. Significant differences were not
observed in the prognosis of different types of primary molars after pulpectomy.
PMID- 28494603
TI - Dental fear and caries in 6-12 year old children in Greece. Determination of
dental fear cut-off points.
AB - AIM: To present: the normative data on dental fear and caries status; the dental
fear cut-off points of young children in the city of Thessaloniki, Greece.
METHODS: Study Design: This is a cross-sectional study with two independent study
groups. A first representative sample consisted of 1484 children from 15 primary
public schools of Thessaloniki. A second sample consisted of 195 randomly
selected age-matched children, all patients of the Postgraduate Paediatric Dental
Clinic of Aristotle University of Thessaloniki. First sample: In order to select
data on dental fear and caries, dental examination took place in the classroom
with disposable mirrors and a penlight. All the children completed the Dental
Subscale of the Children's Fear Survey Schedule (CFSS-DS). Second sample: In
order to define the cut-off points of the CFSS-DS, dental treatment of the 195
children was performed at the University Clinic. Children⁁s dental fear
was assessed using the CFSS-DS and their behaviour during dental treatment was
observed by one calibrated examiner using the Venham scale. STATISTICS:
Statistical analysis of the data was performed with IBM SPSS Statistics 20 at a
statistical significance level of <0.05. RESULTS: First sample: The mean CFSS-DS
score was 27.1±10.8. Age was significantly (p<0.05) related to dental fear.
Mean differences between boys and girls were not significant. Caries was not
correlated with dental fear. Second sample: CFSS-DS< 33 was defined as 'no dental
fear', scores 33-37 as 'borderline' and scores > 37 as 'dental fear'. In the
first sample, 84.6% of the children did not suffer from dental fear (CFSS-DS<33).
CONCLUSION: Dental fear was correlated to age and not to caries and gender. The
dental fear cut-off point for the CFSS-DS was estimated at 37 for 6-12 year old
children (33-37 borderlines).
PMID- 28494604
TI - Use of bioactive materials and limited FOV CBCT in the treatment of a replanted
permanent tooth affected by inflammatory external root resorption: a case report.
AB - BACKGROUND: Inflammatory external root resorption is one of the possible
complications of replantation of an avulsed tooth. Several studies have shown
that limited FOV CBCT is an efficient diagnostic support and in treatment
planning of these cases in paediatric patients because of its high resolution
combined with low radiation doses. The recent literature has suggested that
Biodentine is an effective material for resolution of inflammatory root
resorption. CASE REPORT: This article describes the successful therapy of a
replanted tooth affected by inflammatory root resorption. In the present case, a
CBCT exam was performed to detect the extent of the damage, and the canal was
filled with Biodentine in the apical third. At present, the threated tooth is
asymptomatic, and the twelve months follow-up examination showed healing of
periradicular hard tissues.
PMID- 28494605
TI - Intra-pulpal and subsurface temperature rise during tooth irradiation with 808 nm
diode laser: an in vitro study.
AB - AIM: This in vitro study evaluated the pulpal and subsurface temperatures during
proximal tooth surface irradiation with different settings of an 808 nm diode
laser. MATERIALS AND METHODS: The elevation of pulpal and subsurface temperature
during irradiation was measured using thermocouples positioned in the centre of
the pulp chamber (n=30) and in the centre of a prepared 1.5 mm deep coronal
cavity (n=30). Each sample was irradiated 3 times within one-week interval using
different exposure settings. A temperature increase of 3.5 degrees C was regarded
as critical value for pulpal heath. Results were analysed with one-way ANOVA and
Duncan post hoc tests. Micromorphological investigation by digital microscopy was
carried out for the irradiated and non-irradiated tooth surface. RESULTS
Measurable temperature increase within the pulp chamber (delta PT) and the
subsurface (delta ST) were observed with all laser settings tested. The highest
recorded delta PT and delta ST were 3.1 degrees C and 8.5 degrees C,
respectively. Delivery mode, beam diameter, and exposure time influenced the
temperature rise. No alterations on the enamel surface were observed when
inspected by the digital microscope after undergoing irradiation with the tested
parameters. Cconclusion: From the thermal point of view, under the conditions of
the present study the application of an 808 nm diode laser on the outer surface
of the tooth at 1W in the continuous mode and at 5W in the pulsed mode for two
cycles of 30 s each proved to be safe.
PMID- 28494606
TI - Split-mouth design in Paediatric Dentistry clinical trials.
AB - AIM: The aim of this article was to describe the essential concepts of the split
mouth design, its underlying assumptions, advantages, limitations, statistical
considerations, and possible applications in Paediatric Dentistry clinical
investigation. DISCUSSION: In Paediatric Dentistry clinical investigation, and as
part of randomised controlled trials, the split-mouth design is commonly used.
The design is characterised by subdividing the child's dentition into halves
(right and left), where two different treatment modalities are assigned to one
side randomly, in order to allow further outcome evaluation. Each participant
acts as their own control by making within- patient rather than between-patient
comparisons, thus diminishing inter-subject variability and increasing study
accuracy and power. However, the main problem with this design comprises the
potential contamination of the treatment effect from one side to the other, or
the "carry-across effect"; likewise, this design is not indicated when the oral
disease to be treated is not symmetrically distributed (e.g. severity) in the
mouth of children. Thus, in spite of its advantages, the split-mouth design can
only be applied in a limited number of strictly selected cases. CONCLUSION: In
order to obtain valid and reliable data from split mouth design studies, it is
necessary to evaluate the risk of carry-across effect as well as to carefully
analise and select adequate inclusion criteria, sample-size calculation and
method of statistical analysis.
PMID- 28494607
TI - SCN9A channelopathy associated autosomal recessive Congenital Indifference to
Pain. A case report.
AB - BACKGROUND: Congenital Indifference to Pain (CIP) is a rare condition that
inhibits the ability of patients to perceive physical pain but otherwise keeps
normal sensory modalities. The condition has been mapped to an autosomal
recessive trait to chromosome 2q 24.3 with mutations on the SCN9A gene. CASE
REPORT: A 2 year old Caucasian female presented with CIP. Bite injuries, tongue
wounds and unaccounted dental trauma episodes were frequently reported.
Preventive instructions and possible treatment modalities were discussed with the
parents. CONCLUSION: The cornerstone of treating CIP patients is an extensive
preventive approach alongside regular oral examination at home by parents as well
as routine recall appointments with dentists.
PMID- 28494608
TI - Parenteral nutrition in childhood and consequences for dentition and gingivae.
AB - AIM: Assessment of dentition in children under parenteral nutrition, risk factors
for caries, and dental developmental abnormalities. MATERIALS AND METHODS: The
study involved 63 patients (aged 2.25-16.6 years), i.e. 32 subjects receiving
parenteral nutrition for a mean period of 5.6±2.94 years, and 31 healthy
control subjects. Oral hygiene (OHI-S, PL-I), gingival (GI), and dentition status
(caries, DMFT/dmft, enamel defects, shape alterations), frequency of oral meals
and frequency of cariogenic snacks consumption were evaluated. Medical records
provided information on parenteral meals per week, age parenteral nutrition
started, birth body mass, Apgar score, weight deficiency, and antibiotic therapy
until aged 1 year. The Mann-Whitney test, chi-squared test, and Spearman rank
correlation coefficient were used (p≤0.05). RESULTS: Dental developmental
abnormalities occurred more often in PN subjects (71.87% vs. 25.80%). The
prevalence of caries in PN (56.25% vs. 90.32%) and dmft (2.00±3.30 vs.
4.21±3.33) and DMFT (2.47±4.08 vs. 3.33±3.50) were lower. Positive
caries Spearman's rank correlation coefficients: frequency of oral meals and
frequency of cariogenic snacks consumption, and GI. Negative correlation
coefficients: low birth body mass, antibiotic therapy, and low body mass in the
first year of life. Positive dental developmental abnormality Spearman's
coefficients: low birth body mass, Apgar score < 7, parenteral nutrition
duration, low body mass and antibiotic therapy in the first year of life. Beta-
lactam, aminoglycoside, glycopeptide and nitroimidazole treatments were related
to enamel hypoplasia. CONCLUSION: Parenteral nutrition in childhood is related to
the risk of dental developmental abnormalities, promoted by malnutrition and
antibiotic therapy in infancy. Limiting the number of meals and cariogenic
snacks, and most probably administration of antibiotics, decreases the risk of
caries.
PMID- 28494609
TI - Odontomas in developmental age: confocal laser scanning microscopy analysis of a
case.
AB - BACKGROUND: Odontomas are the most common benign odontogenic tumors (especially
in children and adolescents) and consist of odontogenic ectomesenchyma and
odontogenic epithelium with the formation of dental hard tissues. They are also
simply considered hamartomas. The WHO Classification defines them as complex and
compound odontomas. The diagnosis is often occasional, in conjunction with x-ray
routine examinations, or it is suggested by eruption disorders or abnormal
position of teeth in the dental arch. The mainstay therapy is surgical excision
of the lesion followed by orthodontic treatment to take in the arch the impacted
teeth. CASE REPORT: The aim of this work is the presentation of a case of
mandibular bilateral compound odontoma in a young patient, and the confocal laser
scanning microscopic analysis of the surgical specimens.
PMID- 28494610
TI - Paediatric laser dentistry. Part 1: General introduction.
AB - AIM: Knowledge of the physical characteristics of different laser lights and
optical and thermal properties of oral tissues is very important to understand
the interaction of dental lasers with biological tissues. Choosing the correct
dental laser is crucial to match specific wavelengths with target chromophores of
different tissues; this affinity makes laser irradiation selective and therefore
minimally invasive. Various types of lasers are used in dentistry, offering a
viable alternative to low and high-speed handpieces and surgical blades, and also
minimising fear and discomfort of the patient. Lasers can provide innovative and
minimally invasive therapies in different branches of dentistry including
preventive and restorative dentistry, traumatic injury treatments and surgical
procedures. Laser has also biostimulating and anti-inflammatory effects, as well
as analgesic effect.
PMID- 28494611
TI - Development of a return-to-work planning tool for cancer survivors: Elaboration
d'un outil de planification du retour au travail pour les survivants du cancer.
AB - BACKGROUND: The ability to return to work (RTW) after a cancer diagnosis can
present significant challenges for survivors and can be an important predictor of
their long-term quality of life. Survivors report concerns related to disclosing
their cancer diagnosis, describing ongoing late effects of cancer, and
negotiating workplace accommodations. PURPOSE: This paper outlines the
development of an RTW planning template (RTW-PT) designed to improve
communication with stakeholders involved in the RTW process. Lessons learned
throughout the process of developing the RTW-PT and implications for clinical
practice are presented. KEY ISSUES: The RTW-PT assists the survivor and his or
her health care provider to prioritize job demands during a graded RTW and to
identify potential accommodations. The RTW-PT also helps survivors plan how they
will communicate their RTW needs, particularly with employers and insurance
representatives. IMPLICATIONS: The RTW-PT offers a structured approach to support
communication among stakeholders involved in the RTW process and to assist
survivors in negotiating workplace accommodations.
PMID- 28494612
TI - Oxidative Stress and Inflammation Induced by Environmental and Psychological
Stressors: A Biomarker Perspective.
AB - SIGNIFICANCE: The environment can elicit biological responses such as oxidative
stress (OS) and inflammation as a consequence of chemical, physical, or
psychological changes. As population studies are essential for establishing these
environment-organism interactions, biomarkers of OS or inflammation are critical
in formulating mechanistic hypotheses. Recent Advances: By using examples of
stress induced by various mechanisms, we focus on the biomarkers that have been
used to assess OS and inflammation in these conditions. We discuss the difference
between biomarkers that are the result of a chemical reaction (such as lipid
peroxides or oxidized proteins that are a result of the reaction of molecules
with reactive oxygen species) and those that represent the biological response to
stress, such as the transcription factor NRF2 or inflammation and inflammatory
cytokines. CRITICAL ISSUES: The high-throughput and holistic approaches to
biomarker discovery used extensively in large-scale molecular epidemiological
exposome are also discussed in the context of human exposure to environmental
stressors. FUTURE DIRECTIONS: We propose to consider the role of biomarkers as
signs and to distinguish between signs that are just indicators of biological
processes and proxies that one can interact with and modify the disease process.
Antioxid. Redox Signal. 28, 852-872.
PMID- 28494613
TI - New natural product -an efficient antimicrobial applications of new newly
synthesized pyrimidine derivatives by the electrochemical oxidation of hydroxyl
phenol in the presence of 2-mercapto-6-(trifluoromethyl) pyrimidine-4-ol as
nucleophile.
AB - Some new pyrimidine derivatives have been synthesised by electrochemical
oxidation of catechol (1a) in the existence of 2-mercapto-6-(trifluoromethyl)
pyrimidine-4-ol (3) as a nucleophile in aqueous solution using Cyclic
Voltammetric and Controlled Potential Coulometry. The catechol has been oxidised
to o-quinone through electrochemical method and participative in Michael addition
reaction, leading to the development of some new pyrimidine derivatives. The
products were achieved in good yield with high pureness. The mechanism of the
reaction has been conformed from the Cyclic Voltammetric data and Controlled
Potential Coulometry. After purification, the compounds were characterised using
modern techniques. The synthesised materials were screened for antimicrobial
actions using Gram positive and Gram negative strain of bacteria. These new
synthesised pyrimidine derivatives showed very good antimicrobial activity.
PMID- 28494614
TI - Evaluation of pigments from methanolic extract of Tagetes erecta and Beta
vulgaris as antioxidant and antibacterial agent.
AB - The Total Phenolic Content (TPC), antioxidant and antibacterial activities of
methanolic extract of Marigold flower (MF) (Tagetes erecta) and Beet root (BR)
(Beta vulgaris) were examined. The present work reveals that MF contained greater
amount of TPC (42.5 mg/g GAE) as compared to BR (39.4 mg/g GAE). Methanolic
extract of MF exhibited excellent DPPH free radical scavenging power (IC50 0.0716
mg/mL) and reducing power at 1 mg/mL concentration. Similar results have been
obtained in FTC and TBA method. The results of antibacterial test indicated that
the methanolic extract of MF and BR is significantly effective against both type
of Gram-negative (Escherichia coli, Shigella dysenteriae) and Gram-positive
(Bacillus subtilis, Staphylococcus aureus) bacterial strains. Therefore, the
present study suggests that the Marigold and BR are promising source of herbal
medicinal products with noteworthy antioxidant and antibacterial activity.
PMID- 28494615
TI - Effects of time perspective and self-control on procrastination and Internet
addiction.
AB - Background and aims College students experiencing stress show tendencies to
procrastinate and can develop Internet addiction problems. This study
investigated the structural relationship between time perspective and self
control on procrastination and Internet addiction. Methods College students (N =
377) residing in South Korea completed the following questionnaires: the
Pathological Internet Use Behavior Symptom Scale for Adults, the Zimbardo Time
Perspective Inventory, the Self-Control Rating Scale, and the Aitken
Procrastination Inventory. The sample variance-covariance matrix was analyzed
using AMOS 20.0. Results Time perspective had a direct effect on self-control and
an indirect effect on Internet use and procrastination. In addition, self-control
affected procrastination and Internet use. Conclusions Individuals with a present
oriented time perspective tend to evidence poorer self-control, increasing the
likelihood of procrastination and Internet addiction. Individuals with a future
oriented time perspective, on the other hand, tend to have stronger self-control,
decreasing their risk of procrastination and Internet addiction.
PMID- 28494616
TI - Breakdown of Thalamo-Cortical Connectivity Precedes Spike Generation in Focal
Epilepsies.
AB - Electroencephalography (EEG) spikes and focal epileptic seizures are generated in
circumscribed cerebral networks that have been insufficiently described. For
precise time and spatial domain network characterization, we applied in patients
with focal epilepsy dense array 256-channel EEG recordings with causal
connectivity estimation by using time-resolved partial directed coherence and 3T
magnetic resonance imaging-derived cortical and thalamus integrity
reconstruction. Before spike generation, significant theta and alpha bands driven
information flows alterations were noted from both temporal and frontal lobes to
the thalamus and from the thalamus to the frontal lobe. Medial dorsal and ventral
anterior nuclei of the thalamus were delimited as possible pacemakers. Markedly
reduced thalamic volumes and impaired cortical integrity in widespread areas
predicted the altered information flows. Our data reveal distinct patterns of
connectivity involving the thalamus and frontal cortex that are both directly and
causally involved in spike generation. These structures might play an essential
role in epileptogenesis and could be targeted in future therapeutic approaches.
PMID- 28494617
TI - First report of the in vitro antileishmanial properties of extremophile plants
from the Algarve Coast.
AB - This work reports for the first time the in vitro anti Leishmania infantum
activity of acetone and dichloromethane (DCM) extracts from 25 extremophile
plants from Southern Portugal. DCM extracts from Inula chritmoides and
Spergularia rubra were active against axenic promastigotes and intracellular
amastigotes, had anti-inflammatory properties on lipopolysaccharide (LPS)
stimulated macrophages, inhibited acetylcholinesterase and had no haemolytic
activity on human erythrocytes. Eleven phenolics were identified by high
performance liquid chromatography with diode-array detection (HPLC-DAD) in I.
crithmoides and one phenolic in S. rubra. Isolation and identification of the
active molecules is in progress.
PMID- 28494618
TI - Machine Learning Methods to Predict Diabetes Complications.
AB - One of the areas where Artificial Intelligence is having more impact is machine
learning, which develops algorithms able to learn patterns and decision rules
from data. Machine learning algorithms have been embedded into data mining
pipelines, which can combine them with classical statistical strategies, to
extract knowledge from data. Within the EU-funded MOSAIC project, a data mining
pipeline has been used to derive a set of predictive models of type 2 diabetes
mellitus (T2DM) complications based on electronic health record data of nearly
one thousand patients. Such pipeline comprises clinical center profiling,
predictive model targeting, predictive model construction and model validation.
After having dealt with missing data by means of random forest (RF) and having
applied suitable strategies to handle class imbalance, we have used Logistic
Regression with stepwise feature selection to predict the onset of retinopathy,
neuropathy, or nephropathy, at different time scenarios, at 3, 5, and 7 years
from the first visit at the Hospital Center for Diabetes (not from the
diagnosis). Considered variables are gender, age, time from diagnosis, body mass
index (BMI), glycated hemoglobin (HbA1c), hypertension, and smoking habit. Final
models, tailored in accordance with the complications, provided an accuracy up to
0.838. Different variables were selected for each complication and time scenario,
leading to specialized models easy to translate to the clinical practice.
PMID- 28494619
TI - Improving quality of care for end-stage respiratory disease: Changes in attitude,
changes in service.
AB - The illness trajectory for many patients with severe respiratory disease is
characterized by steady decline. Yet most healthcare resources are poured into
managing acute exacerbations that are only temporarily effective. Further, 'bad
deaths' can result from inappropriate medical interventions at times of crisis.
In this article, we describe a range of changes in attitudes, behaviour and
service provision that together focus on improving quality of care for
respiratory patients with frequent crises. These changes include prognostic
conversations, developing and implementing anticipatory care plans both in
hospital and in the outpatient settings, and establishing a supportive care
clinic devoted to complex disease and optimizing palliative care. The
underpinning philosophy is that common sense and compassion should motivate
broader and more flexible care much more than adherence to the 'curative
restorative' guidelines-based model.
PMID- 28494620
TI - Genetic testing improves identification of transthyretin amyloid (ATTR) subtype
in cardiac amyloidosis.
AB - Amyloidosis is a group of conditions characterized by the accumulation of amyloid
deposits in various tissues. Among these disorders, ATTR amyloidosis occurs
either with or without a TTR pathogenic variant. Treatment for amyloidosis
depends on the subtype, which is often identified through a tissue biopsy
followed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Genetic
testing may be done to confirm these results for patients with ATTR amyloidosis;
however, the necessity of genetic testing after LC-MS/MS has not been evaluated.
A retrospective review identified 153 patients diagnosed with biopsy-proven ATTR
amyloidosis, and 56 of these patients underwent both genetic testing and LC
MS/MS. LC-MS/MS and proteomics correctly reported the mutant peptide and
heterozygosity in 47/56 (84%) cases. It failed to identify two individuals who
were homozygous for the ATTRV122I mutation and failed to detect the following
mutations in six other individuals: ATTRA19D, ATTRF44L, ATTRT60A, ATTRI68L and
ATTRV122I. Therefore, LC-MS/MS is not sufficient to rule out a pathogenic
mutation in cases of ATTR amyloid, and genetic testing should be performed in
most cases of ATTR amyloidosis. Correct recognition of hereditary ATTR
amyloidosis is important for estimating prognosis, proper familial counselling
and guiding use of therapies, such as liver transplantation.
PMID- 28494621
TI - Chinese cross-cultural adaptation and validation of the Foot Function Index as
tool to measure patients with foot and ankle functional limitations.
AB - PURPOSE: To perform a cross-cultural adaptation and validation of the Foot
Function Index (FFI) questionnaire to develop the Chinese version. MATERIALS AND
METHODS: Three hundred and six patients with foot and ankle neuromusculoskeletal
diseases participated in this observational study. Construct validity, internal
consistency and criterion validity were calculated for the FFI Chinese version
after the translation and transcultural adaptation process. RESULTS: Internal
consistency ranged from 0.996 to 0.998. Test-retest analysis ranged from 0.985 to
0.994; minimal detectable change 90: 2.270; standard error of measurement: 0.973.
Load distribution of the three factors had an eigenvalue greater than 1. Chi
square value was 9738.14 (p < 0.001). Correlations with the three factors were
significant between Factor 1 and the other two: r = -0.634 (Factor 2) and r =
0.191 (Factor 1). Foot Function Index (Taiwan Version), Short-Form 12 (Version 2)
and EuroQol-5D were used for criterion validity. Factors 1 and 2 showed
significant correlation with 15/16 and 14/16 scales and subscales, respectively.
CONCLUSIONS: Foot Function Index Chinese version psychometric characteristics
were good to excellent. Chinese researchers and clinicians may use this tool for
foot and ankle assessment and monitoring. Implications for rehabilitation A cross
cultural adaptation of the FFI has been done from original version to Chinese.
Consistent results and satisfactory psychometric properties of the Foot Function
Index Chinese version have been reported. For Chinese speaking researcher and
clinician FFI-Ch could be used as a tool to assess patients with foot disease.
PMID- 28494622
TI - Presence of inflammatory proteins S100A8 and S100A9 in a giant intracranial
aneurysm after flow diverter treatment.
AB - We demonstrate the presence of S100A8 and S100A9 proteins in the wall and
thrombosed lumen of an enlarged intracranial aneurysm after flow diverter
treatment. These proteins have shown to play an important role in vascular
inflammation and may serve as a biomarker and potential therapeutic target for
intracranial aneurysms.
PMID- 28494623
TI - Validity of the Wisconsin Card Sorting Test in patients with stroke.
AB - BACKGROUND: The Wisconsin Card Sorting Test (WCST) is the most widely used
measure for assessing executive functions in patients with stroke. However, no
study has examined the ecological, discriminative and convergent validities of
the WCST in patients with stroke. This study aimed to examine the above
validities of the WCST in patients with stroke. METHODS: Ninety-eight patients
were administered the WCST, two measures of activities of daily living and one
cognitive measure. Seven indexes of the WCST were used in this study. RESULTS:
Two WCST indexes ("total number correct" and "number of categories completed")
had moderate correlations with two measures of activities of daily living
(Pearson's r = 0.39-0.49). The other indexes showed low or moderate correlations
with two measures of activities of daily living (r = 0.26-0.53). The results of
independent t-test showed statistically significant difference between patients
with and without disability for the seven WCST indexes (p = 0.001-0.013) and
nonsignificant differences between patients with different affected regions of
the brain (p > 0.05). Moderate correlations (r = 0.35-0.54) were found among the
seven WCST indexes and one cognitive measure. CONCLUSIONS: The WCST has poor to
adequate ecological validity, acceptable discriminative validity and acceptable
convergent validity in patients with stroke. The two WCST indexes ("total number
correct" and "number of categories completed") are recommended for use to reflect
the degree of living independence in patients with stroke. Implications for
rehabilitation The Wisconsin Card Sorting Test showed poor to adequate ecological
validity, acceptable discriminative validity, and acceptable convergent validity
in patients with stroke. Two indexes of the Wisconsin Card Sorting Test (i.e.,
"total number correct" and "number of categories completed") can adequately
reveal the degrees of living independence in patients with stroke.
PMID- 28494624
TI - An Overview of the Performance Improvement Initiatives by the Ministry of Health
in the Kingdom of Saudi Arabia.
AB - Saudi Arabia's Ministry of Health (MOH) use corporate performance improvement
methodologies to develop and implement performance improvement initiatives
designed to continue building on the Ministry's vision of transforming hospital
operations and instituting a culture of quality and performance focused on the
"patient first" principle. We evaluated the feasibility of setting up a
performance improvement unit (PIU) within the MOH to apply the principles of Lean
Six Sigma and to change management methodologies. The MOH collaborated with
external consultants to implement PIU initiatives in 4 steps: PIU Setup, PIU
Capability Building, High-Impact Project Implementation, and Project
Sustainability and Knowledge Transfer. PIU units were setup across the 13
provinces over 90 days. The process included the promotion of knowledge sharing
to strengthen the skill set of Saudi health care professionals and develop local
performance improvement champions within the MOH who could lead, implement, and
sustain future projects. Implementation was a challenge; though, early results
from the High-Impact Project Implementation phase were encouraging. However, the
sustainability of PIU interventions was poor, with performance improvement
processes returning to baseline levels within 9 months. This case study shows
that PIU implementation is a feasible approach for improving health care delivery
in Saudi Arabia. Poor sustainability despite initial success highlights the need
to further improve the engagement, incentivization, and training of team leaders
and members to achieve long-term success with the program.
PMID- 28494625
TI - S100-alarmins: potential therapeutic targets for arthritis.
AB - INTRODUCTION: In arthritis, inflammatory processes are triggered by numerous
factors that are released from joint tissues, promoting joint destruction and
pathological progression. During inflammation, a novel family of pro-inflammatory
molecules called alarmins is released, amplifying inflammation and joint damage.
Areas covered: With regard to the role of the alarmins S100A8 and S100A9 in the
pathogenesis of arthritis, recent advances and the future prospects in terms of
therapeutic implications are considered. Expert opinion: There is still an urgent
need for novel treatment strategies addressing the local mechanisms of joint
inflammation and tissue destruction, offering promising therapeutic alternatives.
S100A8 and S100A9, which are the most up-regulated alarmins during arthritis, are
endogenous triggers of inflammation, defining these proteins as promising targets
for local suppression of arthritis. In murine models, the blockade of
S100A8/S100A9 ameliorates inflammatory processes, including arthritis, and there
are several lines of evidence that S100-alarmins may already be targeted in
therapeutic approaches in man.
PMID- 28494626
TI - Desoximetasone 0.25% spray, adrenal suppression and efficacy in extensive plaque
psoriasis.
AB - BACKGROUND: In extensive psoriasis, topical corticosteroids are generally only
used to supplement phototherapy and systemic therapy. Spray formulations are
easier than other vehicle preparations to apply and may be an option for treating
extensive psoriasis. OBJECTIVE: To evaluate the potential for hypothalamic
pituitary-adrenal axis suppression and efficacy of topical desoximetasone 0.25%
spray formulation in patients with extensive psoriasis. METHODS: A multicenter,
open label, nonrandomized, clinical trial was conducted. Two groups of 12 adults
with moderate to severe plaque-type psoriasis were treated with 0.25%
desoximetasone spray for 28 days. Physician global assessment (PGA) and body
surface area (BSA) were assessed. Cortisol-induced suppression test was performed
at baseline, day 14 and day 28 to assess safety. RESULTS: No statistically
significant difference was seen in adrenal suppression; odds ratio of 0.779 (p =
.85). The mean PGA improvement from baseline was 1.83 and 1.33 for moderate and
severe psoriasis, respectively. Mean BSA involvement at baseline for moderate and
severe psoriasis was 11% and 23%, respectively, improving to 5% and 19%,
respectively. CONCLUSIONS: Considerable improvement can be achieved with short
term potent topical corticosteroid treatment even in patients with severe,
extensive psoriasis. For such use, topical desoximetasone has less risk of HPA
suppression than does topical clobetasol.
PMID- 28494627
TI - Problem-based learning in occupational therapy curriculum - implications and
challenges.
AB - PURPOSE: Problem-based learning (PBL) is an educational method that fosters self
directed study in small groups. The purpose of this study was to describe the Tel
Aviv University's occupational therapy (OT) program and the challenges
implementing such program. In addition, the study compared the PBL grades
obtained by students who are native Hebrew speakers with those students who are
native Arabic speakers; and, assessed the correlation between the grades in the
PBL course and the grades in the clinical fieldwork studies. METHOD: 166-second
year OT undergraduate students participated. All completed three PBL courses and
seven weeks of clinical fieldwork studies. Data collection included students'
grades in PBL course (based on PBL evaluation forms) and in clinical fieldwork
studies (based on preceptor's evaluation and a written assignment). RESULTS:
Pearson correlations revealed significant correlations between PBL grades and
clinical fieldwork studies grades. T-test analysis between students who are
native Hebrew speakers and those who are native Arabic speakers revealed
significant differences in PBL grades. CONCLUSIONS: Findings imply partial
congruence between students' grades in the PBL course and their achievements in
the fieldwork studies. Findings might suggest that adjustments should be made in
order to assist students from minorities (challenged by language requirements) in
gaining higher grades in the PBL program. Implications for Rehabilitation Problem
Based Learning (PBL) is an educational method, which fosters independent, self
directed study in small groups. PBL studies have the potential to prepare
students for their clinical experience during studies. The PBL program should be
adjusted for students from minorities (challenged by language requirements and
different cultural backgrounds) in order to assist them in gaining more benefits
from the program.
PMID- 28494628
TI - Probabilistic risk assessment of emerging materials: case study of titanium
dioxide nanoparticles.
AB - The development and use of emerging technologies such as nanomaterials can
provide both benefits and risks to society. Emerging materials may promise to
bring many technological advantages but may not be well characterized in terms of
their production volumes, magnitude of emissions, behaviour in the environment
and effects on living organisms. This uncertainty can present challenges to
scientists developing these materials and persons responsible for defining and
measuring their adverse impacts. Human health risk assessment is a method of
identifying the intrinsic hazard of and quantifying the dose-response
relationship and exposure to a chemical, to finally determine the estimation of
risk. Commonly applied deterministic approaches may not sufficiently estimate and
communicate the likelihood of risks from emerging technologies whose uncertainty
is large. Probabilistic approaches allow for parameters in the risk assessment
process to be defined by distributions instead of single deterministic values
whose uncertainty could undermine the value of the assessment. A probabilistic
approach was applied to the dose-response and exposure assessment of a case study
involving the production of nanoparticles of titanium dioxide in seven different
exposure scenarios. Only one exposure scenario showed a statistically significant
level of risk. In the latter case, this involved dumping high volumes of nano
TiO2 powders into an open vessel with no personal protection equipment. The
probabilistic approach not only provided the likelihood of but also the major
contributing factors to the estimated risk (e.g. emission potential).
PMID- 28494629
TI - Cisplatin and paclitaxel co-delivered by folate-decorated lipid carriers for the
treatment of head and neck cancer.
AB - CONTEXT: For head and neck cancer therapy, co-delivery of two drugs, cisplatin
(DDP) plus paclitaxel (PTX), are more effective than single drug therapy. Lipid
carriers are promising drug carriers for anti-cancer delivery. OBJECTIVE: The aim
of this study is to construct a folate (FA) decorated nanostructured lipid
carriers (NLCs) as nanocarriers for DDP and PTX delivery. MATERIALS AND METHODS:
In this study, DDP and PTX were incorporated into NLCs. Folate-PEG-DSPE (FA-PEG
DSPE) was synthesized and decorated the drugs-loaded NLCs (FA-DDP/PTX NLCs).
Their average size, zeta potential, drug encapsulation efficiency, drug loading
capacity, and in vitro drug release were evaluated. Head and neck cancer cells
(FaDu cells) were used for the testing of in vitro cytotoxicity, and in vivo
transfection efficiency of NLC was evaluated on mice bearing FaDu cells model.
RESULTS: The size of FA-DDP/PTX NLCs was around 127 nm, with a positive zeta
potential of 26.7 mV. FA-DDP/PTX NLCs showed the highest cytotoxicity and
synergistic effect of two drugs in head and neck cancer cells (FaDu cells) in
vitro. The in vivo study revealed the greatest anti-tumor activity than all the
other formulations in murine-bearing head and neck cancer model. DISCUSSION AND
CONCLUSION: FA-DDP/PTX NLCs effectively improves anticancer efficiency for head
and neck cancer in vitro and in vivo. The constructed NLCs could be used as a
novel carrier to co-delivery DDP and PTX for head and neck cancer therapy.
PMID- 28494630
TI - Harnessing public domain data to discover and validate therapeutic targets.
AB - INTRODUCTION: Discovering, developing and validating new disease treatments is a
challenging and time-consuming endeavor. Successful drug discovery hinges on
selecting the best drug targets with relevance to human disease and evidence that
modulating them will be beneficial for patients. Open data initiatives are
increasingly placing such knowledge into the public domain. Areas covered: In
this review, the authors discuss emerging resources such as Open Targets which
integrate key information to prioritize target-disease connections. Researchers
can use it, along with other resources, to select potential new therapeutic
targets to initiate drug discovery projects. They also discuss public resources
such as DrugBank and ChEMBL that offer potential tools to interrogate these
targets. Expert opinion: In our opinion, publically available resources are
democratizing and connecting information, enabling disease experts to access and
prioritize targets of interest in ways that were not possible a few years ago.
Moreover, there are several modalities in addition to small molecule perturbation
to modulate a target's activity. Drug discovery scientists can now utilize these
new resources to simultaneously evaluate a much larger number of targets than
previously possible.
PMID- 28494631
TI - Learning from the failures of drug discovery in B-cell non-Hodgkin lymphomas and
perspectives for the future: chronic lymphocytic leukemia and diffuse large B
cell lymphoma as two ends of a spectrum in drug development.
AB - INTRODUCTION: Despite substantial recent advances, there is still an unmet need
for better therapies in B-cell non Hodgkin lymphomas (B-NHL), especially in
relapsed or refractory disease. Many novel targeted drugs have been developed
based on a better molecular understanding of B-NHL. Areas covered: This article
focuses on chronic lymphocytic leukemia (CLL) as a representative for indolent
lymphomas and paradigmatic for the tremendous progress in treating B-NHL on the
one hand and diffuse large B-cell lymphoma (DLBCL) as a representative for
aggressive lymphomas and paradigmatic for many unsolved problems in lymphoma
treatment or the other hand. We highlight salient points in current therapies
targeting genetic, epigenetic, immunological and microenvironmental alterations.
Possible reasons for drug failure in clinical trials like tumor heterogeneity,
clonal evolution and drug resistance mechanisms are discussed. Based thereon,
some perspectives for further drug discovery are given. Expert opinion: In view
of the pathogenetic complexity of lymphomas, therapies targeting exclusively a
single alteration may fail because resistance mechanisms are present either
initially or evolve during treatment. Therefore, future therapies in B-NHL may
have to target the greatest possible number of genetic, immunological or
epigenetic alterations still allowing tolerability and to monitor these
alterations during therapy.
PMID- 28494632
TI - Children's and teachers' perspectives on adjustments needed in school settings
after acquired brain injury.
AB - BACKGROUND: Children with acquired brain injury (ABI) often present with
functional deficits that influence their societal participation and well-being.
Successful reintegration into school calls for individual support to meet each
child's adjustment needs. The adjustment needs of children with ABI in school
settings have not previously been explored. AIM: The objectives of the present
study were (a) to describe adjustment needs in school settings for children with
ABI and (b) to explore differences and similarities between reports from the
children and their teachers. METHODS: In this cross-sectional study, 20 children
with ABI (mean age 12.8 +/- 3.4 years; class grade 1-10) and their teachers were
interviewed individually, using the School Setting Interview (SSI). Data were
analyzed with descriptive and with non-parametric statistics. RESULTS: (a) In the
overall group, children rated that 55.6% of the 16 activities in the SSI needed
no adjustment. The corresponding percentage for teachers was 48.4%. (b) In the
child-teacher pairs, there was a positive relationship between teachers' and
children's responses only in 3 out of 16 school activities and agreement varied
strongly according to the activity in question. CONCLUSIONS AND SIGNIFICANCE: It
is important for occupational therapists and other professionals to specifically
consider adjustment needs relating to school activities from various perspectives
when aiming to provide individualized interventions.
PMID- 28494633
TI - Comparison of in-clinic point-of-care and reference laboratory total thyroxine
immunoassays for diagnosis and post-treatment monitoring of hyperthyroid cats.
AB - Objectives The Catalyst One Chemistry Analyzer (IDEXX Laboratories) is a point-of
care instrument that can measure total thyroxine (TT4) by immunoassay. The aims
of this study were to evaluate the analytic performance of the Catalyst TT4 assay
in feline sera and to examine agreement of the Catalyst TT4 results with those
measured by immunoassay at a veterinary reference laboratory. Methods Assay
precision, reproducibility and linearity were evaluated for the Catalyst TT4
assay. For method comparison, TT4 concentrations in serum samples from 157 cats
(127 hyperthyroid, 30 radioiodine-treated cats) were analyzed by both in-clinic
and reference laboratory methods. Results The Catalyst TT4 demonstrated good
precision and reproducibility (coefficients of variation ?8.5%) and excellent
linearity in the diagnostic range of 6-150 nmol/l. Differences between the two
TT4 methods showed no proportional or fixed bias (Bland-Altman plots) but did
demonstrate greater spread of values at higher TT4 concentrations. Statistical
analysis of percent differences between methods indicated 95% limits of agreement
of +/- 30%. When serum TT4 concentrations were classified as low, high or within
the reference interval (12-50 nmol/l) for each assay, there was strong agreement
(96.8%) in classification between methods. Conclusions and relevance The Catalyst
TT4 assay provided precise serum TT4 concentrations in the 157 samples analyzed,
which agreed well with results provided by a reference laboratory. Cats with
Catalyst TT4 concentrations near decision thresholds (eg, normal vs high) should
either have TT4 concentration repeated a few weeks later and/or undergo further
testing (eg, free T4, serum thyroid-stimulating hormone, thyroid scintigraphy) to
determine thyroid status.
PMID- 28494635
TI - Trends in Management and Mortality in Adults Hospitalized With Cardiac Arrest in
the United States.
AB - BACKGROUND: We sought to examine temporal trends in management (ie, use of
extracorporeal membrane oxygenation [ECMO], therapeutic hypothermia [TH],
coronary angiogram, and percutaneous coronary intervention [PCI]) and in-hospital
mortality in adults hospitalized with cardiac arrest. METHODS: Utilizing the
Nationwide Inpatient Sample, medical history, clinical management, and in
hospital mortality were assessed in 942 495 hospitalizations in adults with
cardiac arrest (identified through International Classification of Diseases-9
codes) from 2006 to 2012. RESULTS: From 2006 to 2012, there was an overall rise
in the use of coronary angiogram (12.8%, 13.0%, 14.7%, 15.0%, 14.3%, 14.7%, and
15.8%), PCI (7.5%, 7.1%, 8.4%, 8.1%, 8.1%, 8.4%, and 8.9%), TH (0.2%, 0.3%, 0.6%,
1.2%, 1.9%, 2.8%, and 3.0%), and ECMO (0.1%, 0.1%, 0.1%, 0.2%, 0.2%, 0.3%, and
0.4%; P < .001 for all). In-hospital mortality significantly decreased over the 7
year study period (65.5%, 63.4%, 59.3%, 57.9%, 57.0%, 56.0%, and 56.3% from 2006
to 2012). In multivariable analysis, a 31% decrease in mortality was accompanied
by a concomitant 24% and 27% increase in coronary angiogram and PCI,
respectively, during the study period. Therapeutic hypothermia and ECMO were
associated with an approximate 11-fold and 7-fold increase, respectively, from
2006 to 2012. The strongest predictors of use of ECMO, TH, coronary angiogram,
and PCI were younger age and the presence of coronary artery disease. CONCLUSION:
During 2006 to 2012, a decline in mortality was accompanied by a steady rise in
the use of ECMO, TH, coronary angiogram, and PCI in adults hospitalized with
cardiac arrest. Patients of younger age and with coronary artery disease were
more likely to receive these advanced therapies.
PMID- 28494634
TI - Changing place of death in children who died after discharge from paediatric
intensive care units: A national, data linkage study.
AB - BACKGROUND: Although child mortality is decreasing, more than half of all deaths
in childhood occur in children with a life-limiting condition whose death may be
expected. AIM: To assess trends in place of death and identify characteristics of
children who died in the community after discharge from paediatric intensive care
unit. DESIGN: National data linkage study. SETTING/PARTICIPANTS: All children
resident in England and Wales when admitted to a paediatric intensive care unit
in the United Kingdom (1 January 2004 and 31 December 2014) were identified in
the Paediatric Intensive Care Audit Network dataset. Linkage to death certificate
data was available up to the end of 2014. Place of death was categorised as
hospital (hospital or paediatric intensive care unit) or community (hospice, home
or other) for multivariable logistic modelling. RESULTS: The cohort consisted of
110,328 individuals. In all, 7709 deaths occurred after first discharge from
paediatric intensive care unit. Among children dying, the percentage in-hospital
at the time of death decreased from 83.8% in 2004 to 68.1% in 2014; 852 (0.8%) of
children were discharged to palliative care. Children discharged to palliative
care were eight times more likely to die in the community than children who died
and had not been discharged to palliative care (odds ratio = 8.06 (95% confidence
interval = 6.50-10.01)). CONCLUSIONS: The proportion of children dying in
hospital is decreasing, but a large proportion of children dying after discharge
from paediatric intensive care unit continue to die in hospital. The involvement
of palliative care at the point of discharge has the potential to offer choice
around place of care and death for these children and families.
PMID- 28494636
TI - Higher iron bioavailability of a human-like collagen iron complex.
AB - Iron deficiency remains a public health problem around the world due to low iron
intake and/or bioavailability. FeSO4, ferrous succinate, and ferrous glycinate
chelate are rich in iron but have poor bioavailability. To solve the problem of
iron deficiency, following previous research studies, a thiolated human-like
collagen-ironcomplex supplement with a high iron content was prepared in an
anaerobic workstation. In addition, cell viability tests were evaluated after
conducting an MTT assay, and a quantitative analysis of the thiolated human-like
collagen-iron digesta samples was performed using the SDS-PAGE method coupled
with gel filtration chromatography. The iron bioavailability was assessed using
Caco-2 cell monolayers and iron-deficiency anemia mice models. The results showed
that (1) one mole of thiolated human-like collagen-iron possessed approximately
35.34 moles of iron; (2) thiolated human-like collagen-iron did not exhibit
cytotoxity and (3) thiolated human-like collagen- iron digesta samples had higher
bioavailability than other iron supplements, including FeSO4, ferrous succinate,
ferrous glycine chelate and thiolated human-like collagen-Fe iron. Finally, the
iron bioavailability was significantly enhanced by vitamin C. These results
indicated that thiolated human-like collagen-iron is a promising iron supplement
for use in the future.
PMID- 28494637
TI - Does Anxiety Enhance or Hinder Attentional and Impulse Control in Youth With
ADHD? An ERP Analysis.
AB - OBJECTIVE: Youth with ADHD and comorbid anxiety (ADHD+ANX) experience increased
social and academic impairment compared with youth with ADHD without anxiety
(ADHD). Group differences in attentional and impulse control may underlie this
increased impairment. Examination of group differences using behavioral measures
of attentional and impulse control has yielded inconsistent findings. This study
explored group differences using event-related potentials (ERPs), which provide
neural information concerning early information processing. METHOD: ERPs (early
frontal positivity [EFP], N2) were collected while youth aged 11 to 17 with ADHD
( n = 31) and ADHD+ANX ( n = 35) completed a visual and an auditory computer
task. RESULTS: Compared with the ADHD group, the ADHD+ANX group exhibited larger
N2 amplitudes to no-go stimuli and larger EFP amplitudes to target auditory
stimuli, with variable attention allocation to nontarget stimuli. CONCLUSION: The
addition of anxiety to ADHD appears to alter early attentional processing, which
may be an important aspect of this comorbidity.
PMID- 28494638
TI - An environmental scan of emergency response systems and services in remote First
Nations communities in Northern Ontario.
AB - BACKGROUND: Approximately 24,000 Ontarians live in remote Indigenous communities
with no road access. These communities are a subset of Nishnawbe Aski Nation
(NAN), a political grouping of 49 First Nations communities in Northern Ontario,
Canada. Limited information is available regarding the status of emergency care
in these communities. OBJECTIVE: We aimed to understand emergency response
systems, services, and training in remote NAN communities. DESIGN: We used an
environmental scan approach to compile information from multiple sources
including community-based participatory research. This included the analysis of
data collected from key informant interviews (n=10) with First Nations community
health leaders and a multi-stakeholder roundtable meeting (n=33) in October 2013.
RESULTS: Qualitative analysis of the interview data revealed four issues related
to emergency response systems and training: (1) inequity in response capacity and
services, (2) lack of formalised dispatch systems, (3) turnover and burnout in
volunteer emergency services, and (4) challenges related to first aid training.
Roundtable stakeholders supported the development of a community-based emergency
care system to address gaps. CONCLUSIONS: Existing first response, paramedical,
and ambulance service models do not meet the unique geographical, epidemiological
and cultural needs in most NAN communities. Sustainable, context-appropriate, and
culturally relevant emergency care systems are needed.
PMID- 28494639
TI - Photocatalytic degradation of polyvinylpyrrolidone in aqueous solution using
TiO2/H2O2/UV system.
AB - The photocatalytic degradation of high molecular weight polyvinylpyrrolidone
(PVP), a water-soluble polymer, using a TiO2/H2O2/UV system was studied in an
annular photoreactor using a mercury vapor lamp (125 W) as the radiation source.
The effect of the initial hydrogen peroxide concentration and the operating
conditions, such as initial concentration of PVP, photocatalyst dosage and
initial pH, on the reaction rate was also evaluated. It was observed that the
efficiency of the TiO2/H2O2/UV system was 33% higher than that of a system
without H2O2, reaching total organic carbon removals of above 80% in 6 h of
reaction, depending on the experimental conditions. The optimal photocatalyst
dosage was found to be 0.50 g L-1. Also, the results demonstrate that the
reaction rate increases as the pH and initial concentration of PVP decrease. This
treatment can be carried out successfully under optimal conditions and enhance
the biodegradability of the organic matter remaining at the end of the
application of the TiO2/H2O2/UV system, as assessed by biochemical oxygen
demand/chemical oxygen demand measurements.
PMID- 28494640
TI - Identification of 3-MCPD esters to verify the adulteration of extra virgin olive
oil.
AB - The adulteration of olive oil is an important issue around the world. This paper
reports an indirect method by which to identify 3-monochloropropane-1,2-diol (3
MCPD) esters in olive oils. Following sample preparation, the samples were spiked
with 1,2-bis-palmitoyl-3-chloropropanediol standard for analysis using gas
chromatograph-tandem mass spectrometry. The total recovery ranged from 102.8% to
105.5%, the coefficient of variation ranged from 1.1% to 10.1%, and the limit of
quantification was 0.125 mg/kg. The content of 3-MCPD esters in samples of
refined olive oil (0.97-20.53 mg/kg) exceeded those of extra virgin olive oil
(non-detected to 0.24 mg/kg). These results indicate that the oil refining
process increased the content of 3-MCPD esters, which means that they could be
used as a target compound for the differentiation of extra virgin olive oil from
refined olive oil in order to prevent adulteration.
PMID- 28494641
TI - Establishment and Evaluation of Patient-Specific Virtual Ureteroscopy in
Assisting Flexible Ureteroscopy for Urolithiasis.
AB - OBJECTIVES: To establish virtual ureteroscopy (VU) through computed tomography
urography (CTU) data from patients with upper urinary tract (UUT) stones
indicated for flexible ureteroscopy (fURS) and to validate its effectiveness.
METHODS: Patient-specific VU generation was accomplished through incorporating
CTU data into specialized software (Crusher) developed on the open access
Visualization Tools Kit (VTK). These were then presented to fURS experts and
novice urologists for evaluation and comparison using modified Likert-type
questionnaire of 10-point rating scales (1 = not at all useful/not at all
realistic/poor, 10 = very useful/very realistic/ excellent). RESULTS: Face and
content validation of VU from 5 fURS experts in 3 different centers: overall
usefulness 7.4 +/- 0.5, graphics 7.4 +/- 0.5, intrarenal anatomy 8.4 +/- 0.5,
stone details 7.8 +/- 0.4, usefulness in surgical planning and training 7.6 +/-
0.9. Significant increase of detection in the number of calyces and stones was
found from using CTU only to CTU-VU combined in the novice group ( P = .000).
Before VU observation, novices found much fewer calyces and stones than experts (
P = .004 and .000, respectively). However, this gap disappeared after VU
observation ( P = .327 and .292, respectively). VU feedback from the novices was
superb. CONCLUSIONS: Establishing patient-specific VU through CTU data from renal
stone patients is feasible. The present VU can significantly improve novice
urologists' comprehension of intrarenal anatomy and stone information before fURS
procedures. Face and content validity is also proved. This novel modality may
serve as an important tool for fURS surgical planning, navigation, and training.
PMID- 28494642
TI - Normal anatomy and variations in the confluence of sinuses using digital
subtraction angiography.
AB - OBJECTIVES: The configuration of the confluence of sinuses differs not only
between individuals, but also between the two brain hemispheres, making the
anatomical classification of this region difficult. In this study, we evaluated
the anatomy of the confluence of sinuses and ascertained the accuracy and
usefulness of digital subtraction angiography (DSA) in the evaluation of cerebral
veins. METHODS: Bilateral carotid and vertebral artery angiographies were
performed in 500 adult patients to evaluate the anatomy of the confluence of
sinuses and contributory venous sinuses. We appraised the anatomy of the sinuses
adjacent to the confluence, the lateralization of venous draining into the
transverse sinuses (TSs), the communications between the TSs, and the
presentation of the occipital sinus (OS). RESULTS: Based on the anatomical
descriptions of Osborn's Brain (Diagnostic Cerebral Angiography, 2nd edition), we
delineated 10 different configurations of the confluence of sinuses that showed
connections among the superior sagittal sinus, the straight sinus, and the left
and right TSs. Right side dominant transverse sinus accounted for 49% of the
cases. Direct communication between the TSs accounted for 46.4% of the cases.
Indirect communication accounted for 51.6% of the case, and absence of
communication between the left and the right TS accounted for 2%. Lastly, the
presence of OS was observed in 6% of the cases. CONCLUSION: DSA promises to be an
effective technique for studying the anatomy and normal variations of the
confluence of sinuses, providing useful information for the diagnosis of cerebral
venous diseases, and ensuring safer surgical procedures.
PMID- 28494643
TI - Randomised clinical trial of early specialist palliative care plus standard care
versus standard care alone in patients with advanced cancer: The Danish
Palliative Care Trial.
AB - BACKGROUND: Beneficial effects of early palliative care have been found in
advanced cancer, but the evidence is not unequivocal. AIM: To investigate the
effect of early specialist palliative care among advanced cancer patients
identified in oncology departments. SETTING/PARTICIPANTS: The Danish Palliative
Care Trial (DanPaCT) (ClinicalTrials.gov NCT01348048) is a multicentre randomised
clinical trial comparing early referral to a specialist palliative care team plus
standard care versus standard care alone. The planned sample size was 300. At
five oncology departments, consecutive patients with advanced cancer were
screened for palliative needs. Patients with scores exceeding a predefined
threshold for problems with physical, emotional or role function, or
nausea/vomiting, pain, dyspnoea or lack of appetite according to the European
Organisation for Research and Treatment of Cancer Quality of Life Questionnaire
(EORTC QLQ-C30) were eligible. The primary outcome was the change in each
patient's primary need (the most severe of the seven QLQ-C30 scales) at 3- and 8
week follow-up (0-100 scale). Five sensitivity analyses were conducted. Secondary
outcomes were change in the seven QLQ-C30 scales and survival. RESULTS: Totally
145 patients were randomised to early specialist palliative care versus 152 to
standard care. Early specialist palliative care showed no effect on the primary
outcome of change in primary need (-4.9 points (95% confidence interval -11.3 to
+1.5 points); p = 0.14). The sensitivity analyses showed similar results.
Analyses of the secondary outcomes, including survival, also showed no
differences, maybe with the exception of nausea/vomiting where early specialist
palliative care might have had a beneficial effect. CONCLUSION: We did not
observe beneficial or harmful effects of early specialist palliative care, but
important beneficial effects cannot be excluded.
PMID- 28494644
TI - The Alpha 7 Nicotinic Acetylcholine Receptor of Deciduous Dental Pulp Stem Cells
Regulates Osteoclastogenesis During Physiological Root Resorption.
AB - The physiological root resorption of deciduous teeth is a normal phenomenon, but
the mechanisms underlying this process are still unclear. In this study,
deciduous dental pulp stem cells (DDPSCs) and permanent dental pulp stem cells
(DPSCs) were derived from deciduous teeth and normal permanent teeth at different
stages of resorption. In the middle stage of root resorption, DDPSCs exhibited an
increase in the ability to induce osteoclast differentiation. Activation of the
alpha 7 nicotinic acetylcholine receptor (alpha7 nAChR) by secretory mammalian Ly
6 urokinase-type plasminogen activator receptor-associated protein 1 (SLURP-1)
caused a significant increase in the expression levels of NF-kappaB, receptor
activator of nuclear factor-kappa B ligand (RANKL), and the ratio of
RANKL/osteoprotegerin (OPG). These effects were inhibited by alpha-bungarotoxin
(alpha-BTX). Furthermore, the expression levels of RANKL/OPG were significantly
reduced following inhibition of NF-kappaB. High-strength, dynamic positive
pressure increased the expression of SLURP-1 and alpha7 nAChR in DDPSCs in the
stable stage. These data indicated that mechanical stress stimulated the
expression of SLURP-1 and alpha7 nAChR in DDPSCs. Additionally, SLURP-1 activated
alpha7 nAChR, thereby upregulating the expression of NF-kappaB and enhancing its
activity, thus regulating RANKL/OPG expression and affecting the ability of
DDPSCs to influence osteoclastogenesis, which likely enhances root resorption and
leads to the physiological loss of deciduous teeth.
PMID- 28494645
TI - Whistle-blowing process in healthcare: From suspicion to action.
AB - BACKGROUND: Whistle-blowing is an ethical activity that tries to end wrongdoing.
Wrongdoing in healthcare varies from inappropriate behaviour to illegal action.
Whistle-blowing can have negative consequences for the whistle-blower, often in
the form of bullying or retribution. Despite the wrongdoing and negative tone of
whistle-blowing, there is limited literature exploring them in healthcare.
OBJECTIVE: The aim was to describe possible wrongdoing in Finnish healthcare and
to examine whistle-blowing processes described on the basis of the existing
literature in healthcare as perceived by healthcare professionals. RESEARCH
DESIGN: The study was a cross-sectional descriptive survey. The data were
collected using the electronic questionnaire Whistle-blowing in Health Care and
analysed statistically. Participants and research context: A total of 397 Finnish
healthcare professionals participated, 278 of whom had either suspected or
observed wrongdoing in healthcare, which established the data for this article.
Ethical considerations: Ethical approval was obtained from the Ethics Committee
of the University (20/2015). Permission to conduct the study was received
according to the organisation's policies. FINDINGS: Wrongdoing occurs in
healthcare, as 96% of the participants had suspected and 94% had observed
wrongdoing. Regarding the frequency, wrongdoing was suspected (57%) and observed
(52%) more than once a month. Organisation-related wrongdoing was the most common
type of wrongdoing (suspected 70%, observed 66%). In total, two whistle-blowing
processes were confirmed in healthcare: (1) from suspicion to consequences
occurred to 27%, and (2) from observation to consequences occurred to 37% of the
participants. DISCUSSION AND CONCLUSION: Wrongdoing occurs in healthcare quite
frequently. Whistle-blowing processes were described based on the existing
literature, but two separate processes were confirmed by the empirical data. More
research is needed on wrongdoing and whistle-blowing on it in healthcare.
PMID- 28494646
TI - A Randomized Study Comparing Stem Cell Transplantation Versus Conventional
Therapy for Low- and Intermediate-Risk Myelodysplastic Syndromes Patients.
AB - The treatment of myelodysplastic syndromes (MDS) involves improving patient
survival and quality of life (QoL) and decreasing the likelihood of progression
to AML. Although the treatment outcomes of MDS remain unsatisfactory, few
comparative studies have been performed while comparing the outcomes of low-risk
and intermediate-risk patients treated with supportive care and chemotherapeutics
to those of patients treated with allogeneic hematopoietic stem cell
transplantation (allo-HSCT). Therefore, we designed a clinical control study to
compare the outcomes of supportive care and chemotherapeutics versus allo-HSCT
treatment in MDS patients. A total of 182 patients with MDS were enrolled in the
study, including 91 in the no-HSCT (control) group and 91 in the allo-HSCT group.
The complete remission (CR) rate in the allo-HSCT group was significantly higher
than that in the control group (53.8% vs. 33.0%; P < 0.05). The QoL of patients
in the HSCT group was much higher than that in the control group (53.8% vs.
37.4%; P < 0.05). The overall survival (OS) rates were 79.0% and 56.0% (P < 0.05)
in the HSCT group and the control group, respectively. In conclusion, a high-dose
fludarabine (Flu), busulfan (Bu), cyclophosphamide (CTX)-based conditioning
regimen was well tolerated and significantly speeded hematopoietic recovery. In
addition, this regimen increased procedure-related toxicity and improved QoL and
OS.
PMID- 28494647
TI - Which dimensions of impulsivity are related to problematic practice of physical
exercise?
AB - Background and aims Problematic practice of physical exercise (PPPE) has been
suggested to be a behavioral addiction. Impulsivity represents a core dimension
of behavioral addictions. However, little is known about impulsivity facets in
PPPE. The aim of this study was to investigate the role of impulsivity facets in
PPPE. Methods A total of 684 students (between 18 and 25 years) took part in this
study and filled up a battery of questionnaire, which consisted of following
measures - Global Physical Activity Questionnaire, Exercise Dependence Scale -
Revised, and the UPPS Impulsive Behavior Scale. Multiple regression analyses were
utilized to investigate the predictive role of each impulsivity facet in PPPE.
Results Age, the total level of physical activity per day, sex (male), negative
urgency, and sensation seeking were found to be significant predictors of PPPE. A
categorical analysis of PPPE revealed that negative urgency, positive urgency,
and sensation seeking were significantly higher in the dependent category of
PPPE. Discussion and conclusions Associations to negative urgency and sensation
seeking might indicate that PPPE serves to regulate or alleviate negative affect
or aversive emotional states. Thus, PPPE could be conceptualized as a short-term
coping strategy dedicated to relieving negative affective states, like other
maladaptive behaviors such as binge eating, binge drinking, or compulsive buying.
PMID- 28494648
TI - Social networking addiction, attachment style, and validation of the Italian
version of the Bergen Social Media Addiction Scale.
AB - Aim Research into social networking addiction has greatly increased over the last
decade. However, the number of validated instruments assessing addiction to
social networking sites (SNSs) remains few, and none have been validated in the
Italian language. Consequently, this study tested the psychometric properties of
the Italian version of the Bergen Social Media Addiction Scale (BSMAS), as well
as providing empirical data concerning the relationship between attachment styles
and SNS addiction. Methods A total of 769 participants were recruited to this
study. Confirmatory factor analysis (CFA) and multigroup analyses were applied to
assess construct validity of the Italian version of the BSMAS. Reliability
analyses comprised the average variance extracted, the standard error of
measurement, and the factor determinacy coefficient. Results Indices obtained
from the CFA showed the Italian version of the BSMAS to have an excellent fit of
the model to the data, thus confirming the single-factor structure of the
instrument. Measurement invariance was established at configural, metric, and
strict invariances across age groups, and at configural and metric levels across
gender groups. Internal consistency was supported by several indicators. In
addition, the theoretical associations between SNS addiction and attachment
styles were generally supported. Conclusion This study provides evidence that the
Italian version of the BSMAS is a psychometrically robust tool that can be used
in future Italian research into social networking addiction.
PMID- 28494649
TI - Herbicidal activity of pure compound isolated from rhizosphere inhabiting
Aspergillus flavus.
AB - In the quest for bioactive natural products of fungal origin, Aspergillus flavus
was isolated from rhizosphere of Mentha piperita using Potato Dextrose Agar (PDA)
and Czapec Yeast Broth (CYB) nutrient media for metabolites production. In total,
three different metabolites were purified using HPLC/LCMS and the structures were
established using 500 Varian NMR experiments. Further the isolated metabolites in
different concentrations (10, 100, 1000 MUg/mL) were tested for herbicidal
activity using Completely Randomized design (CRD) against the seeds of Silybum
marianum and Avena fatua which are major threats to wheat crop in Pakistan. Among
the isolated metabolites, one compound was found active against the test weed
species whose activity is reported in the present work. The chemical name of the
compound is 2-(1, 4-dihydroxybutan-2-yl)-1, 3-dihydroxy-6, 8-dimethoxyanthracene
9, 10(4aH, 9aH)-dione with mass of 388. Results showed that all seeds germinated
in control treatment; however, with the metabolite treated, the growth was
retarded to different levels in all parts of the weeds. At a dose of 1000 MUg/mL
of the pure compound, 100% seeds of S. marianum and 60% seeds of A. fatua were
inhibited. Interestingly, the pure compound exhibited less inhibition of 10%
towards the seeds of common wheat (Triticum aestivum).
PMID- 28494650
TI - Spinal metastatic lung adenocarcinoma with dural invasion and concomitant
intradural and extradural components: a case report.
AB - We report the case of a metastatic lung carcinoma that had metastasized to the
thoracic extradural space and penetrated the dura, resulting in a combined extra
and intradural spinal tumour. To our knowledge this is the first such report of a
metastatic lung adenocarcinoma demonstrating direct dural invasion.
PMID- 28494651
TI - Isolation and structure elucidation of a new compound from the fungus Aspergillus
flavipes PJ03-11.
AB - A new diphenyl ether 3-methylpentyl-2, 4-dichloroasterrate (2), along with a
known diphenyl ether butyl 2, 4-dichloroasterrate (1) were isolated from the
metabolites of a wetland fungus Aspergillus flavipes. PJ03-11. The structures of
1 and 2 were determined by extensive NMR and HR-ESI-MS experiments. Compounds 1
and 2 showed weak cytotoxic activity, but both of them showed no antimicrobial
activity.
PMID- 28494652
TI - The Keap1-Nrf2 Stress Response Pathway Promotes Mitochondrial Hyperfusion Through
Degradation of the Mitochondrial Fission Protein Drp1.
AB - AIMS: Mitochondrial function is coupled to metabolic and survival pathways
through both direct signaling cascades and dynamic changes in mitochondrial
morphology. For example, a hyperfused mitochondrial reticulum is activated upon
cellular stress and is protective against cell death. As part of a genome-wide
small inhibitory ribonucleic acid screen, we identified the central redox
regulator, Keap1, as a novel regulator of mitochondrial morphology. Here, we
aimed to determine the mechanism through which redox signaling and Keap1 mediate
changes in mitochondrial morphology. RESULTS: We found that the Nrf2
transcription factor is required for mitochondrial hyperfusion induced by
knockdown of Keap1. Nrf2, which is negatively regulated by Keap1, mediates the
cell's response to stress by controlling the expression of several hundred genes,
including proteasome expression. We next showed that increased proteasome
activity, a result of increased Nrf2 activity, is responsible for the degradation
of the mitochondrial fission protein Drp1, which occurs in an ubiquitin
independent manner. INNOVATION: Our study described a novel pathway by which Nrf2
activation, known to occur in response to increased oxidative stress, decreases
mitochondrial fission and contributes to a hyperfused mitochondrial network.
CONCLUSION: This study has identified the Keap1-Nrf2 nexus and modulation of
proteasomal activity as novel avenues to inhibit mitochondrial fission. These
findings are important, because inhibiting mitochondrial fission is a promising
therapeutic approach to restore the balance between fission and fusion, which is
attractive for an increasing number of disorders linked to mitochondrial
dysfunction. Antioxid. Redox Signal. 27, 1447-1459.
PMID- 28494653
TI - Patterns and Yearly Time Trends in the Use of Radiation Therapy During the Last
30 Days of Life Among Patients With Metastatic Rectal Cancer in the United States
From 2004 to 2012.
AB - PURPOSE: Although radiation therapy (RT) can provide palliative benefits for
patients with metastatic rectal cancer, its role at the end of life remains
unclear. The objective of this study was to assess sociodemographic and clinical
factors associated with the use of RT during the last 30 days of life and to
evaluate yearly time trends in RT utilization among stage IV patients with rectal
cancer. METHODS: The 2004 to 2012 National Cancer DataBase was queried for
patients with metastatic rectal cancer who had a documented death during follow
up. A Bayesian multilevel logistic regression model was used to characterize
predictive factors and yearly time trends associated with RT use in the last 30
days of life. RESULTS: Among 10 431 patients who met inclusion criteria, 345 (3%)
received RT during the last 30 days of life. Factors independently associated
with RT use included older age, female sex, African American race, nonprivate
insurance, higher comorbidity burden, and worse grade. The odds of RT use at the
end of life decreased by 28% between 2007 and 2009 (odds ratio [OR] = 0.72, 95%
Credible Interval (CI) = 0.58-0.93), but then increased by 16% from 2010 to 2012
(OR = 1.16, 95% CI = 1.13-1.33), relative to 2004 to 2006. CONCLUSION: Radiation
therapy use for patients with metastatic rectal cancer is beneficial, and efforts
to optimize its appropriate use are important. Several factors associated with RT
use during the last 30 days of life included disparities in sociodemographic and
clinical subgroups. Research is needed to understand the underlying causes of
these inequalities and the role of predictive models in clinical decision-making.
PMID- 28494654
TI - New formulations of tacrolimus and prevention of acute and chronic rejections in
adult kidney-transplant recipients.
AB - : Introduction: As tolerance is not yet achievable, the kidney-transplanted
patients have to take on a daily-basis immunosuppressive drugs in order to avoid
acute rejection-AR-. The cornerstone of immunosuppression relies on tacrolimus
therapy which is potentially nephrotoxic. Areas Covered: We identified from the
studies published in the recent years those who were reporting on AR in de novo
kidney-transplant recipients under tacrolimus-based therapy, as well as those who
reported on the attempt to minimize tacrolimus-therapy. RESULTS: There are many
formulations of tacrolimus: immediate-release (Prograf(r)), slow-release
(Advagraf(r)), or extended-release (Envarsus(r)). All demonstrate a very good
efficacy in preventing AR episodes. Studies in which tacrolimus was minimized or
even weaned-off have shown that it was unsafe, i.e. in resulting in AR episode
and/or de novo donor-specific alloantibodies. Recent data show that Tacrobell(r),
a generic of tacrolimus, was as efficient as Prograf(r) in the short- and long
term. Expert-opinion: Tacrolimus-based immunosuppression is very effective in
preventing rejection in kidney-transplant recipients. It might be associated with
nephrotoxicity, that can be reduced by avoiding tacrolimus trough levels too high
in the long-term. Conversely, tacrolimus ultraminimization should not be
attempted.
PMID- 28494656
TI - In-Service Training for Increasing Teachers' ADHD Knowledge and Self-Efficacy.
AB - OBJECTIVE: The aim of this article is to evaluate the efficacy of a brief in
service training workshop at increasing primary school teachers' ADHD knowledge
and sense of self-efficacy. METHOD: Teachers from 10 schools participated in the
study ( n = 274) and were allocated into either an intervention or waitlist
control group. Teachers' ADHD knowledge and self-efficacy were assessed following
the provision of a brief training workshop on ADHD. Knowledge and self-efficacy
retention were also assessed at a 1-month follow-up. RESULTS: Within the
intervention group, ADHD knowledge and self-efficacy increased following the
intervention (both ps < .001). Knowledge increased more than twofold, from very
low to high levels, although increases in self-efficacy were more modest. Both
knowledge and self-efficacy decreased at the 1-month follow-up but, nevertheless,
remained higher than baseline levels ( p < .001). CONCLUSION: Results demonstrate
that a brief training workshop can increase primary school teachers' ADHD
knowledge and self-efficacy. Whilst increases in self-efficacy were modest, our
findings suggest that a brief professional development intervention can be
utilized to greatly increase teachers' ADHD knowledge, providing a cost
effective, practical solution to address this well-evidenced gap in teachers'
training and knowledge about the disorder.
PMID- 28494657
TI - Ward sister in Swansea is RCNi Nurse of the Year.
AB - The ultimate prize at the 2017 RCNi Nurse Awards has gone to Melanie Davies for
her work championing the wellbeing of people with learning disabilities.
PMID- 28494658
TI - 'Be honest with yourself'.
AB - What is your job? I am trainee consultant practitioner emergency care at Health
Education England in Wessex. The three-year consultant practitioner development
programme prepares practitioners for consultant practice. It provides high-level
training and mentoring across professional leadership, education, service
development and expert clinical practice. It also combines academic study with
clinical placements in different settings and trusts.
PMID- 28494660
TI - Young people's changing demands for emergency services.
AB - A ten-year study has highlighted some eye-opening statistics concerning children
and emergency care: significantly more children are now being admitted for
jaundice, acute bronchitis, acute and chronic tonsillitis, and viral infections.
PMID- 28494661
TI - Duty of care has never been more relevant.
AB - The recent attack on Westminster Bridge in London sparked an immediate response
from the emergency services who tried to save the lives of the many people who
had been mowed down by a single perpetrator. The emergency teams should be
commended for their work during such an extreme and difficult situation.
PMID- 28494662
TI - Make your vote count at the general election.
AB - Before any general election the NHS is an important subject of every manifesto,
where each party sets out the aims - some may say promises - that it will follow
if it is elected: its 'big sell'.
PMID- 28494663
TI - What is person-centred care and can it be achieved in emergency departments?
AB - Contemporary nursing in all disciplines focuses on the concept of person-centred
care, and how this improves patients' experiences. This article defines person
centred care, and considers whether it can be upheld in emergency departments,
which are facing unprecedented pressures, and in which staff resilience and
morale are challenged continually.
PMID- 28494664
TI - Handwashing.
AB - Our clinical update on new National Institute for Health and Care Excellence
(NICE) guidance on tackling antimicrobial resistance.
PMID- 28494665
TI - Remote clinical decision-making: a clinician's definition.
AB - Aims Remote clinical decision-making (RCDM), commonly known as 'telephone triage'
or 'hear and treat', describes clinicians' non-face-to-face involvement with
patient care, and is an established strategy in UK ambulance services for
managing increasing demand. However, there is no suitable definition of RCDM that
fully explains the roles undertaken by clinicians in 999 hubs, or for its use as
an ambulance quality indicator (AQI). The aim of this study, which is part of a
larger evaluation of a new RCDM module in higher education, is to determine how
clinicians define RCDM. Methods Three participants were asked, during semi
structured interviews, to define RCDM. The interviews were recorded, transcribed
and thematically analysed. Results Clinicians do not focus on outcomes when
defining RCDM, but on the efficacy of the process and the appropriateness of the
determined outcome. Conclusion There is no precise description of the role of
healthcare professionals in 999 clinical hubs, but there is a need for role
clarity, for employees and organisations. The study questions the suitability of
the definition of hear and treat as an AQI, as it does not appear to represent
fully the various duties undertaken by 999 clinical hub healthcare professionals.
More research is needed to consider the definition of RCDM in all its forms.
PMID- 28494666
TI - Unlocking the NMC code of conduct.
AB - A new student resource, Unlocking the Code, aims to help nursing students get to
grips with the Nursing and Midwifery Council (NMC) code of conduct.
PMID- 28494667
TI - Meet Drew - winner in the Child Health category.
AB - 'My goal as a nurse is to ensure that every child attending our department is
given the best care possible. We should treat the families as if they were our
own, and I knew we were not good enough at dealing with sepsis.'
PMID- 28494655
TI - Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide
Association Study of Anorexia Nervosa.
AB - OBJECTIVE: The authors conducted a genome-wide association study of anorexia
nervosa and calculated genetic correlations with a series of psychiatric,
educational, and metabolic phenotypes. METHOD: Following uniform quality control
and imputation procedures using the 1000 Genomes Project (phase 3) in 12 case
control cohorts comprising 3,495 anorexia nervosa cases and 10,982 controls, the
authors performed standard association analysis followed by a meta-analysis
across cohorts. Linkage disequilibrium score regression was used to calculate
genome-wide common variant heritability (single-nucleotide polymorphism [SNP]
based heritability [h2SNP]), partitioned heritability, and genetic correlations
(rg) between anorexia nervosa and 159 other phenotypes. RESULTS: Results were
obtained for 10,641,224 SNPs and insertion-deletion variants with minor allele
frequencies >1% and imputation quality scores >0.6. The h2SNP of anorexia nervosa
was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based
heritability arises from common genetic variation. The authors identified one
genome-wide significant locus on chromosome 12 (rs4622308) in a region harboring
a previously reported type 1 diabetes and autoimmune disorder locus. Significant
positive genetic correlations were observed between anorexia nervosa and
schizophrenia, neuroticism, educational attainment, and high-density lipoprotein
cholesterol, and significant negative genetic correlations were observed between
anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes.
CONCLUSIONS: Anorexia nervosa is a complex heritable phenotype for which this
study has uncovered the first genome-wide significant locus. Anorexia nervosa
also has large and significant genetic correlations with both psychiatric
phenotypes and metabolic traits. The study results encourage a
reconceptualization of this frequently lethal disorder as one with both
psychiatric and metabolic etiology.
PMID- 28494669
TI - Bedside handovers 'improve rapport'.
AB - Staff at a hospital emergency assessment unit have introduced bedside nurse
handovers to boost interaction with patients.
PMID- 28494668
TI - Hands-on senior clinicians 'could reduce demand'.
AB - Having senior clinicians on hand to assess emergency department (ED) patients can
transform patient demand, according to a new report from the Institute of
Healthcare Management.
PMID- 28494670
TI - Number of children being admitted rises.
AB - Emergency department admissions for babies and young children have risen by
almost one third in a decade, a report has found.
PMID- 28494671
TI - More MS nurses needed to reduce waiting lists.
AB - New analysis shows the number of emergency department admissions for people with
multiple sclerosis (MS) continues to rise, costing the NHS millions.
PMID- 28494672
TI - Nursing and Healthcare Research at a Glance Glasper Alan Rees Colin Nursing and
Healthcare Research at a Glance 224pp L26.99 Wiley Blackwell 9781118778791
1118778790 [Formula: see text].
AB - This book could appeal to all levels of nursing researchers, academics, students
and anyone trying to rise up the clinical research ladder.
PMID- 28494673
TI - Law and Ethics in Nursing and Healthcare: An Introduction Avery Graham Law and
Ethics in Nursing and Healthcare: An Introduction 392pp L26.99 Sage 9781412961745
1412961742 [Formula: see text].
AB - The aim of this book, now in its second edition, is to set out the main concepts
of law and ethics in healthcare. Its content is up to date, comprehensive and
practical, and encourages readers to seek out further resources.
PMID- 28494675
TI - Cornstarch gel found to be an alternative for ultrasound use.
AB - Ultrasound images produced using cornstarch-based (known as cornflour in the UK)
gel are of similar quality to those using commercial gel, according to a study in
Emergency Medicine Journal.
PMID- 28494674
TI - Should nurses receive formal commendations?
AB - On 22 March news broke that an incident had occurred at the Palace of Westminster
in London. The Metropolitan Police, London Ambulance Service and the Helicopter
Emergency Medical Service responded and, as details emerged, it became clear
there had been a terrorist attack.
PMID- 28494679
TI - First rib fracture treatment should focus on other injuries.
AB - Management of patients with fractures of the first rib should focus on
identifying and treating associated life-threatening injuries, says a study in
Emergency Medicine Journal.
PMID- 28494680
TI - End of life care in emergency departments: a review of the literature.
AB - Providing end of life care (EOLC) in emergency departments (EDs) is challenging
because of minimal resources, lack of staff education and outdated models of
care. Dynamic, chaotic environments like EDs require systematic, clear and
concise principles and goals for patient care. Death in EDs is inevitable,
therefore staff should be equipped to provide optimal care to this vulnerable
patient group. This article reviews the literature on the barriers to providing
EOLC in EDs, and makes recommendations for clinical practice and further
research. EOLC refers to care of terminally and critically ill patients in their
final days and hours of life.
PMID- 28494681
TI - Acute and sub-chronic toxicity of Cajanus cajan leaf extracts.
AB - CONTEXT: The leaves of Cajanus cajan (L.) Millsp. (Fabaceae) have diverse
bioactivities, but little safety data are reported. OBJECTIVE: This study
examines the toxicological profiles of C. cajan leaf extracts. MATERIALS AND
METHODS: The leaves were extracted by water or 90% ethanol to obtain water or
ethanol extract (WEC or EEC). EEC was suspended in water and successively
fractionated into dichloroform and n-butanol extracts (DEC and BEC). Marker
compounds of the extracts were monitored by high-performance liquid
chromatography (HPLC). Kunming mice were administered with a single maximum
acceptable oral dose (15.0 g/kg for WEC, EEC and BEC and 11.3 g/kg for DEC) to
determine death rate or maximal tolerated doses (MTDs). In sub-chronic toxicity
investigation, Sprague-Dawley rats were orally given WEC or EEC at 1.5, 3.0 or
6.0 g/kg doses for four weeks and observed for two weeks after dosing to
determine toxicological symptoms, histopathology, biochemistry and haematology.
RESULTS: Flavonoids and stilbenes in the extracts were assayed. In acute toxicity
test, no mortality and noted alterations in weight and behavioural abnormality
were observed, and the maximum oral doses were estimated as MTDs. In sub-chronic
toxicity study, no mortality and significant variances in haematological and
biochemical parameters or organ histopathology were observed, but increased
kidney weight in 3.0 g/kg WEC- or 3.0 and 6.0 g/kg EEC-treated female rats, and
reduced testes and epididymis weight in EEC-treated male rats were recorded.
These changes returned to the level of control after recovery period. CONCLUSION:
Acute and sub-chronic toxicity of Cajanus cajan leaf extracts was not observed.
PMID- 28494682
TI - Operative transvaginal hydrolaparoscopy improve ovulation rate after clomiphene
failure in polycystic ovary syndrome.
AB - Aim of our study was to assess the ovulation rate, with mid-luteal progesterone
level and ultrasound follicles monitoring, in PCOS CC-resistant patients
undergone transvaginal hydrolaparoscopy ovarian drilling. A prospective
observational study was carried out in 123 PCOS, infertile, CC-resistant patients
who undergone THL ovarian drilling. Each woman was evaluated by hormonal
measurement, and ultrasound evaluation during 6 months follow-up. Progesterone
serum levels were assessed on days 20-24 of the cycle after surgical treatment.
Pg levels >3 ng/mL were considered as ovulation. Ovulation frequency and the
highest mean follicular diameters during the monitoring were recorded. 117
patients complete the study, since six patients were lost to follow-up. Mean
follicular diameter during ovulation monitoring was 16.37 mm. Ovulation rate at
the follow up was 64.1% one month after treatment, 79.5% after three months and
82.9% after six months. 28 patients conceived during follow-up period. Pregnancy
rate was 70.1%. Our study has shown that THL ovarian drilling improves ovulation
and pregnancy rate in women with CC-resistant PCOS. We believe that this approach
should be offered as second-line therapy at all PCOS CC-resistant women who fail
the medical methods of ovulation induction.
PMID- 28494683
TI - What is clearance worth? Patients' stated risk tolerance for psoriasis
treatments.
AB - PURPOSE: The purpose of this study was to provide quantitative evidence of
patients' tolerance for therapeutic risks associated with psoriasis treatments
that could offer psoriasis improvements beyond the PASI 75 benchmark. MATERIALS
AND METHODS: We used a discrete-choice experiment in which respondents chose
between competing psoriasis treatments characterized by benefits (i.e. reduced
plaque severity, reduced plaque area), risks (i.e. 10-year risk of tuberculosis,
10-year risk of death from infection), and treatment regimen. We analyzed choice
data using random-parameters logit models for psoriasis affecting the body, face,
or hands. RESULTS: Of 927 eligible members of the National Psoriasis Foundation
who completed the survey, 28% were unwilling to accept any greater risk of
treatment-related infection mortality. Among the remaining 72%, respondents were
willing to accept higher risks of infection-related mortality associated with
treatment to completely remove plaques covering only 1% of the body, compared to
reducing lesions from 10 to 1% of the affected area. This finding was more
pronounced for lesions on the face. CONCLUSIONS: Most patients placed greater
value on eliminating even very small plaques compared to avoiding treatment
related risks. The perceived importance of complete versus near-complete
clearance was stronger than previously documented.
PMID- 28494684
TI - Effectiveness of Telementoring in Surgery Compared With On-site Mentoring: A
Systematic Review.
AB - BACKGROUND: Mentorship is important but may not be feasible for distance
learning. To bridge this gap, telementoring has emerged. The purpose of this
systematic review was to evaluate the effectiveness of telementoring compared
with on-site mentoring. METHODS: A search was done up to March 2015. Studies were
included if they used telementoring between surgeons during a clinical encounter
and if they compared on-site mentoring and telementoring. RESULTS: A total of 11
studies were included. All reported no difference in complication rates, and 9
(82%) reported similar operative times; 4 (36%) reported technical issues, which
was 3% of the total number of cases in the 11 studies. No study reported on
higher levels of evidence for effectiveness of telementoring as an educational
intervention. CONCLUSION: Studies reported that telementoring is associated with
similar complication rates and operative times compared with on-site mentoring.
However, the level of evidence to support the effectiveness of telementoring as a
training tool is limited. There is a need for studies that provide evidence for
the equivalence of the effectiveness of telementoring as an educational
intervention in comparison with on-site mentoring.
PMID- 28494685
TI - Greek Surgeon Pavlos Ioannou's Possible Influence on William Halsted's Famous
Radical Mastectomy.
AB - Pavlos Ioannou performed an innovative surgical operation for breast cancer in
Vienna University Hospital in 1861. A few years later, after his return to
Greece, an operation performed on his closest friend's child, which led to fatal
complications, led him to retire from surgical practice. William Halsted
travelled to Europe in order to master European surgery, including at Vienna
University, and about 20 years later he published his famous method for radical
mastectomy, which appears to be identical to Ioannou's operation. This article
debates whether Halsted studied Ioannou's method in the archives of Vienna
University (and was encouraged by Ioannou's retirement to develop this
technique), whether he learned about it through his peers, or whether this was
simply a historical coincidence.
PMID- 28494688
TI - Evolution in psoriasis management.
PMID- 28494686
TI - Clinical pharmacology, efficacy, and safety of selexipag for the treatment of
pulmonary arterial hypertension.
AB - INTRODUCTION: Selexipag is the first oral, non-prostanoid, selective prostacyclin
receptor (IP receptor) agonist, approved for the long-term treatment of pulmonary
arterial hypertension (PAH) in adult patients. Areas covered: This article
reviews the clinical pharmacology, efficacy, and safety of selexipag in the
treatment of PAH. Expert opinion: Selexipag is the first oral drug that
selectively targets the prostacyclin pathway, and has evidence of long-term
efficacy and safety. In the global phase 3 study GRIPHON (NCT01106014) in PAH
patients, selexipag significantly reduced the risk of the primary composite
outcome of morbidity/mortality (M/M). The adverse events in the selexipag group
were consistent with the known side effects of prostacyclin, including headache,
nausea, jaw pain, and diarrhea. Importantly, selexipag was efficacious and safe
irrespective of whether or not patients were already receiving other PAH
therapies. With selexipag approval, triple oral combination therapy addressing
three important pathways is available for patients with PAH. Selexipag has one
major metabolite, ACT-333679, which is also a selective IP receptor agonist, with
37-fold higher potency than selexipag. Pharmacokinetic properties of ACT-333679
permit twice-daily dosing of selexipag, providing a more convenient treatment
compared to prostacyclin or its analogs. For patients with moderate hepatic
impairment a once-daily regimen is recommended.
PMID- 28494690
TI - Acrylamide in thermal-processed carbohydrate-rich foods from Chinese market.
AB - Acrylamide content in food market in China was determined with the goal to
evaluate related health concern. In this survey, products of rice, potato corn,
wheat as well as dried fruit slices and instant foods were analysed. All these
types of thermal-processed carbohydrate-rich foods were frequently consumed in
China. They were purchased from markets in Zhejiang province and analysed using a
liquid chromatography tandem/mass spectrometry method. Acrylamide was detected in
94.3% of 105 investigated samples, ranging from 10 to 3649 MUg/kg with an average
value of 231 MUg/kg and a median of 114 MUg/kg. In this study, high levels were
found in potato products (564 +/- 285 MUg/kg), corn products (524 +/- 187 MUg/kg)
and instant foods (180 +/- 35 MUg/kg) while low levels were measured in rice
products (82 +/- 17 MUg/kg), wheat products (96 +/- 29 MUg/kg) and dried fruit
slices (83 +/- 13 MUg/kg).
PMID- 28494691
TI - Central poststroke pain: A systematic review.
AB - Background Physical, psychological, and/or social impairment can result after a
stroke and can be exacerbated by pain. One type of pain after stroke, central
poststroke pain, is believed to be due to primary central nervous system
mechanisms. Estimated prevalence of central poststroke pain ranges widely from 8%
to 55% of stroke patients, suggesting a difficulty in reliably, accurately, and
consistently identifying central poststroke pain. This may be due to the absence
of a generally accepted definition. Aim We aimed to clarify the role of thalamic
strokes and damage to the spinothalamic pathway in central poststroke pain
patients. Also, we aimed to gain a current understanding of anatomic substrates,
brain imaging, and treatment of central poststroke pain. Summary of review Two
independent reviewers identified 10,144 publications. Based on Preferred
Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we extracted
data from 23 papers and categorized the articles' aims into four sections:
somatosensory deficits, pathway stimulation, clinical trials, and brain imaging.
Conclusions Our systematic review suggests that damage to the spinothalamic
pathway is associated with central poststroke pain and this link could provide
insights into mechanisms and treatment. Moreover, historical connection of
strokes in the thalamic region of the brain and central poststroke pain should be
reevaluated as many studies noted that strokes in other regions of the brain have
high occurrence of central poststroke pain as well.
PMID- 28494693
TI - Keeping up with stroke meetings from around the world.
PMID- 28494692
TI - Capsular warning syndrome as a manifestation of isolated middle cerebral artery
dissection in a Latin American patient.
PMID- 28494694
TI - Antagonizing dabigatran by idarucizumab in cases of ischemic stroke or
intracranial hemorrhage in Germany - A national case collection.
AB - Background Idarucizumab is a monoclonal antibody fragment with high affinity for
dabigatran that reverses its anticoagulant effects within minutes. It may exhibit
the potential for patients under dabigatran therapy suffering ischemic stroke to
regain eligibility for thrombolysis with rt-PA and may inhibit lesion growth in
patients with intracerebral hemorrhage on dabigatran. Aims To provide insights
into the clinical use of idarucizumab in patients under effective dabigatran
anticoagulation presenting with signs of ischemic stroke or intracranial
hemorrhage. Methods Retrospective data collected from German
neurological/neurosurgical departments administering idarucizumab following
product launch from January to August 2016 were used. Results Thirty-one patients
presenting with signs of stroke received idarucizumab in 22 stroke centers.
Nineteen patients treated with dabigatran presented with ischemic stroke and 12
patients suffered from intracranial bleeding. In patients receiving rt-PA
thrombolysis following idarucizumab, 79% benefitted from i.v. thrombolysis with a
median improvement of five points in NIHSS. No bleeding complications occurred.
Hematoma growth was observed in 2 out of 12 patients with intracranial
hemorrhage. The outcome was favorable with a median NIHSS improvement of 5.5
points and mRS 0-3 in 67%. Overall, mortality was low with 6.5% (one patient in
each group). Conclusion Administration of rt-PA after reversing dabigatran
activity with idarucizumab in case of ischemic stroke is feasible, easy to
manage, effective, and appears to be safe. In dabigatran-associated intracranial
hemorrhage, idarucizumab has the potential to prevent hematoma growth and improve
outcome. Idarucizumab represents a new therapeutic option for patients under
dabigatran treatment presenting with ischemic stroke or intracranial hemorrhage.
PMID- 28494696
TI - Oxidative injuries induced by maternal low-protein diet in female brainstem.
AB - Many studies have shown that a maternal low-protein diet increases the
susceptibility of offspring to cardiovascular disease in later-life. Moreover, a
lower incidence of cardiovascular disease in females than in males is understood
to be largely due to the protective effect of high levels of estrogens throughout
a woman's reproductive life. However, to our knowledge, the role of estradiol in
moderating the later-life susceptibility of offspring of nutrient-deprived
mothers to cardiovascular disease is not fully understood. The present study is
aimed at investigating whether oxidative stress in the brainstem caused by a
maternal low-protein diet administered during a critical period of fetal/neonatal
brain development (i.e during gestation and lactation) is affected by estradiol
levels. Female Wistar rat offspring were divided into four groups according to
their mothers' diets and to the serum estradiol levels of the offspring at the
time of testing: (1) 22 days of age/control diet: (2) 22 days of age/low-protein
diet; (3) 122 days of age/control diet: (4) 122 days of age/low-protein diet.
Undernutrition in the context of low serum estradiol compared to undernutrition
in a higher estradiol context resulted in increased levels of oxidative stress
biomarkers and a reduction in enzymatic and non-enzymatic antioxidant defenses.
Total global oxy-score showed oxidative damage in 22-day-old rats whose mothers
had received a low-protein diet. In the 122-day-old group, we observed a decrease
in oxidative stress biomarkers, increased enzymatic antioxidant activity, and a
positive oxy-score when compared to control. We conclude from these results that
following a protein deficiency in the maternal diet during early development of
the offspring, estrogens present at high levels at reproductive age may confer
resistance to the oxidative damage in the brainstem that is very apparent in pre
pubertal rats.
PMID- 28494697
TI - Talking Circles to Improve Diabetes Self-care Management.
AB - Purpose The purpose of this study was to determine if the use of both the Talking
Circles (TCs) and diabetes self-management education (DSME) results in better
adherence and outcomes for diabetes self-management than DSME alone in American
Indians (AIs) with type 2 diabetes mellitus (T2DM). Methods A quasiexperimental,
mixed-methods approach was used for AIs with uncontrolled T2DM, defined by an A1C
> 7.0%. The experimental group (n = 20) participated in a TC and received DSME.
The control group (n = 19) received only DSME. Talking Circles were audio-taped
and analyzed qualitatively. Quantitative data were analyzed using the generalized
estimating equation and Fisher exact test for all study participants every 3
months for 1 year. Results Themes identified by TC participants were
spirituality, gratitude, and sharing. Major topics of discussion were the
experiences of living with T2DM, including challenges and coping. Evidence of
positive trends for the experimental group who received the TC intervention
included lower systolic blood pressure, lower A1C, lower weight over time, and
increased adherence without incentives. Conclusion Talking Circles may have
utility in improving adherence in AI adults with uncontrolled T2DM. Further
studies are warranted, including extending the use of the TCs after completion of
DSME sessions.
PMID- 28494695
TI - The Role of Integrin alpha6 (CD49f) in Stem Cells: More than a Conserved
Biomarker.
AB - Stem cells have the capacity for self-renewal and differentiation into
specialized cells that form and repopulated all tissues and organs, from
conception to adult life. Depending on their capacity for differentiation, stem
cells are classified as totipotent (ie, zygote), pluripotent (ie, embryonic stem
cells), multipotent (ie, neuronal stem cells, hematopoietic stem cells,
epithelial stem cells, etc.), and unipotent (ie, spermatogonial stem cells).
Adult or tissue-specific stem cells reside in specific niches located in, or
nearby, their organ or tissue of origin. There, they have microenvironmental
support to remain quiescent, to proliferate as undifferentiated cells (self
renewal), and to differentiate into progenitors or terminally differentiated
cells that migrate from the niche to perform specialized functions. The presence
of proteins at the cell surface is often used to identify, classify, and isolate
stem cells. Among the diverse groups of cell surface proteins used for these
purposes, integrin alpha6, also known as CD49f, may be the only biomarker
commonly found in more than 30 different populations of stem cells, including
some cancer stem cells. This broad expression among stem cell populations
indicates that integrin alpha6 may play an important and conserved role in stem
cell biology, which is reaffirmed by recent demonstrations of its role
maintaining self-renewal of pluripotent stem cells and breast and glioblastoma
cancer stem cells. Therefore, this review intends to highlight and synthesize new
findings on the importance of integrin alpha6 in stem cell biology.
PMID- 28494698
TI - Extemporaneously preparative biodegradable injectable polymer systems exhibiting
temperature-responsive irreversible gelation.
AB - On clinical application of biodegradable injectable polymer (IP) systems, quick
extemporaneous preparation of IP formulations and longer duration time gel state
after injection into the body are the important targets to be developed.
Previously, we had reported temperature-responsive covalent gelation systems via
bio-orthogonal thiol-ene reaction by 'mixing strategy' of amphiphilic
biodegradable tri-block copolymer (tri-PCG) attaching acryloyl groups on both
termini (tri-PCG-Acryl) with reactive polythiol. In other previous works, we
found 'freeze-dry with PEG/dispersion' method as quick extemporaneous preparation
method of biodegradable IP formulations. In this study, we applied this quick
preparative method to the temperature-triggered covalent gelation system. The
instant formulation (D-sample) could be prepared by 'freeze-dry with
PEG/dispersion' just mixing of tri-PCG-Acryl micelle dispersion and tri-PCG/DPMP
micelle dispersion with PEG, that can be prepared in 30 s from the dried samples.
The obtained D-sample showed irreversible gelation and long duration time of gel
state, which was basically the same as the formulations prepared by the usual
heating dissolution method (S-sample). Interestingly, the D-sample could maintain
its sol state for a longer time (24 h) after preparing the formulation at r.t.
compared with the S-sample, which became a gel in 3 h after preparing. The IP
system showed good biocompatibility and long duration time of the gel state after
subcutaneous implantation. These characteristics of D-samples, quick
extemporaneous preparation and high stability in the sol state before injection,
would be very convenient in a clinical setting.
PMID- 28494699
TI - Lens Capsule Perforation Without Inflammation in 4 Rabbits From Intravitreal
Injection Studies.
AB - Historically, it was thought that lens protein was sequestered, and injury to the
lens capsule causing release of lens material into the eye would always result in
ocular inflammation. Currently, it is believed that lens antigens are recognized
as self, subject to normal T-cell tolerance. Three different single-dose
intravitreal injection/implantation studies of 4 different test materials,
ranging from 4 to 6 weeks in length, were performed in New Zealand White rabbits.
The test materials included polymer microspheres, polymer rods, a solvent, and a
hydrogel. Intravitreal injection/implantation procedures were performed on day 1,
and indirect ophthalmoscopy and slit-lamp biomicroscopy examinations were
performed by board-certified veterinary ophthalmologists periodically throughout
the course of each study. None of the affected animals received corticosteroids
or other immunomodulatory agents during the course of the studies. Four rabbits
had perforation of the posterior lens capsule during the injection/implantation
procedure on day 1, visible on clinical ophthalmic examination as lens capsule
alterations described as "lens hits" and/or incipient posterior cataracts.
Findings on slit-lamp biomicroscopy examination were limited to vitreous cells in
2 of the animals, although not centered on the area of lens capsule disturbance.
Histologically, there was no evidence of inflammation in association with
extruded lens protein material in any of the affected eyes. These results
indicate that iatrogenic damage to the lens capsule during aseptically performed
intravitreal injections/implantations does not appear to induce inflammation in
rabbits.
PMID- 28494700
TI - Invasive Front Grading and Epithelial-Mesenchymal Transition in Canine Oral and
Cutaneous Squamous Cell Carcinomas.
AB - Oral and cutaneous tissues are the most frequent origin in canine squamous cell
carcinoma (SSC). In SCC, changes in adhesion molecule expression and transition
from epithelial to mesenchymal phenotype are thought to be important in
development of invasive behavior of neoplastic cells at the leading front of the
tumor. We therefore investigated histological invasive front grading and
epithelial-mesenchymal transition (EMT) in both oral SCCs and cutaneous SCCs. EMT
was assessed by evaluating immunohistochemical expression of E-cadherin, beta
catenin, desmoglein, vimentin, and N-cadherin. Regardless of the anatomic
location, invasive front grading resulted in higher histological grades than
grading of the surface. Most oral SCCs were of significantly higher histologic
grade than cutaneous SCCs ( P < .01). Expression of E-cadherin, beta-catenin, and
desmoglein was significantly lower in oral SCC compared with cutaneous SCC ( P <
.01). A significant association was found between invasive front grading and loss
of E-cadherin, beta-catenin, and desmoglein ( P < .01). Also, vimentin-positive
neoplastic cells had low immunoreactivity of these adhesion molecules, and a few
of these neoplastic cells were positive for N-cadherin. These results suggest not
only E-cadherin and beta-catenin but also desmoglein as markers for predicting
biological behavior of canine SCC. Depending on their primary sites, EMT
correlates with biological behavior and therefore histological grade of canine
SCC. We suggest that combining invasive front grading with assessment of
immunohistochemical expression of E-cadherin, beta-catenin, and desmoglein may
allow more accurate prediction of biological behavior of canine SCCs.
PMID- 28494701
TI - Spindle Cell Lipoma in Dogs.
AB - Spindle cell lipoma (SCL) is a benign neoplasm of the adipose tissue that may
resemble an undifferentiated soft tissue sarcoma (STS). This report describes the
histopathological features of 6 SCLs in dogs. All SCLs were located in the
subcutis and were composed of bland, occasionally vacuolated spindle cells
intermixed with ropey collagen and myxoid matrix. Sudan IV stain performed in 1
case demonstrated the lipid content of vacuoles. Mature adipocytes represented
less than 10% of the neoplasm in 3 cases and were absent in the remaining 3.
Average mitotic count in 10 high-power fields was 0.17. Neoplastic cells were
immunohistochemically positive for vimentin and negative for S100 protein, smooth
muscle actin, factor VIII-ra, and MDM2. Awareness of SCL and its specific
histopathological features is essential to diagnose this specific tumor. Further
studies are needed to document the biological behavior of these tumors in dogs.
PMID- 28494702
TI - An Australian Newcastle Disease Virus With a Virulent Fusion Protein Cleavage
Site Produces Minimal Pathogenicity in Chickens.
AB - Newcastle disease is an important disease of poultry caused by virulent strains
of Newcastle disease virus (NDV). During the 1998 to 2002 outbreaks of Newcastle
disease in Australia, it was observed that the mild clinical signs seen in some
chickens infected with NDV did not correlate with the viruses' virulent fusion
protein cleavage site motifs or standard pathogenicity indices. The pathogenicity
of 2 Australian NDV isolates was evaluated in experimentally challenged chickens
based on clinical evaluation, histopathology, immunohistochemistry, and molecular
techniques. One of these virus isolates, Meredith/02, was shown to induce only
very mild clinical signs with no mortalities in an experimental setting, in
contrast to the velogenic Herts 33/56 and Texas GB isolates. This minimal
pathogenicity was associated with decreased virus replication and antigen
distribution in tissues. This demonstrates that the Australian Meredith/02 NDV,
despite possessing a virulent fusion protein cleavage site, did not display a
velogenic phenotype.
PMID- 28494703
TI - Globule Leukocytes and Other Mast Cells in the Mouse Intestine.
AB - Only 2 major mast cell (MC) subtypes are commonly recognized in the mouse: the
large connective tissue mast cells (CTMCs) and the mucosal mast cells (MMCs).
Interepithelial mucosal inflammatory cells, most commonly identified as globule
leukocytes (GLs), represent a third MC subtype in mice, which we term
interepithelial mucosal mast cells (ieMMCs). This term clearly distinguishes
ieMMCs from lamina proprial MMCs (lpMMCs) while clearly communicating their
common MC lineage. Both lpMMCs and ieMMCs are rare in normal mouse intestinal
mucosa, but increased numbers of ieMMCs are seen as part of type 2 immune
responses to intestinal helminth infections and in food allergies. Interestingly,
we found that increased ieMMCs were consistently associated with decreased
mucosal inflammation and damage, suggesting that they might have a role in
controlling helminth-induced immunopathology. We also found that ieMMC
hyperplasia can develop in the absence of helminth infections, for example, in
Treg-deficient mice, Arf null mice, some nude mice, and certain graft-vs-host
responses. Since tuft cell hyperplasia plays a critical role in type 2 immune
responses to intestinal helminths, we looked for (but did not find) any direct
relationship between ieMMC and tuft cell numbers in the intestinal mucosa. Much
remains to be learned about the differing functions of ieMMCs and lpMMCs in the
intestinal mucosa, but an essential step in deciphering their roles in mucosal
immune responses will be to apply immunohistochemistry methods to consistently
and accurately identify them in tissue sections.
PMID- 28494705
TI - Brucellosis in Endangered Hector's Dolphins (Cephalorhynchus hectori).
AB - Brucella spp infections of marine mammals are often asymptomatic but have been
associated with reproductive losses and deaths. Zoonotic infections originating
from marine isolates have also been described. Hector's dolphins (Cephalorhynchus
hectori) are an endangered species with a declining population, and the role of
infectious disease in population dynamics is not fully understood. In this study,
27 Hector's dolphins found dead around the New Zealand coastline between November
2006 and October 2010 were evaluated for lesions previously associated with
cetacean brucellosis. Tissues were examined using histological,
immunohistochemical, and molecular (polymerase chain reaction [PCR]) techniques.
Seven of 27 dolphins (26%) had at least 1 tissue that was positive on PCR for
Brucella spp. Lesions consistent with brucellosis were present in 10 of 27 (37%)
dolphins, but in 8 of these dolphins Brucella infection could not be demonstrated
in lesional tissues. Two dolphins (7%) were diagnosed with active brucellosis: 1
female with placentitis and metritis, and 1 stillborn male fetus. Brucella
identified in these 2 dolphins had genetic similarity (99%) to Brucella
pinnipedialis. The omp2a gene amplicon from the uterus of the female had 100%
homology with ST27 genotype isolates from a human in New Zealand and a bottlenose
dolphin of Pacific origin. The remaining 5 PCR-positive dolphins were assessed as
having asymptomatic or latent infection. While most Brucella infections
identified in this study appeared to be subclinical, the finding of 2 dolphins
with reproductive disease due to Brucella infection suggests that this disease
has the potential to affect reproductive success in this species.
PMID- 28494704
TI - Endoscopic Cytology for the Diagnosis of Chronic Enteritis and Intestinal
Lymphoma in Dogs.
AB - Although cytology is a rapid diagnostic procedure in dogs, the cytologic criteria
of endoscopic biopsies for chronic enteritis and intestinal lymphoma are not well
defined. An immediate diagnosis using cytology would benefit patients by enabling
prompt initiation of therapy. The objective of this study was to investigate the
correlation between the results of endoscopic cytology and histopathology. In
this study, 167 dogs with clinical signs of chronic gastrointestinal disease were
included. On the basis of histopathology, the following diagnoses were
determined: lymphocytic-plasmacytic enteritis in 93 dogs; eosinophilic enteritis
in 5 dogs; small cell intestinal lymphoma in 45 dogs; and large cell intestinal
lymphoma in 24 dogs. Two clinical pathologists retrospectively evaluated the
endoscopic cytology of squash-smear preparations. The cytologic diagnoses of
inflammation, small cell lymphoma, and large cell lymphoma were based on the
severity of lymphocyte infiltration, the size of infiltrated lymphocytes, and
eosinophil/mast cell infiltration. The clinical severity score was significantly
increased along with the degree of lymphocyte infiltration evaluated by cytology.
The cytologic diagnosis was in complete agreement with the histopathologic
diagnosis in 136 of 167 (81.4%) cases. For the differentiation between enteritis
and lymphoma, endoscopic cytology had a sensitivity of 98.6%, a specificity of
73.5%, a positive predictive value of 72.3%, and a negative predictive value of
98.6%. The log-rank test and Cox regression analysis showed that the results of
cytology predicted the prognosis. These results suggest that endoscopic cytology
is a useful technique to aid diagnosis of intestinal inflammation and lymphoma in
dogs.
PMID- 28494706
TI - Ranid Herpesvirus 3 and Proliferative Dermatitis in Free-Ranging Wild Common
Frogs (Rana Temporaria).
AB - Amphibian pathogens are of current interest as contributors to the global decline
of amphibians. However, compared with chytrid fungi and ranaviruses,
herpesviruses have received relatively little attention. Two ranid herpesviruses
have been described: namely, Ranid herpesvirus 1 (RHV1) and Ranid herpesvirus 2
(RHV2). This article describes the discovery and partial characterization of a
novel virus tentatively named Ranid herpesvirus 3 (RHV3), a candidate member of
the genus Batrachovirus in the family Alloherpesviridae. RHV3 infection in wild
common frogs (Rana temporaria) was associated with severe multifocal epidermal
hyperplasia, dermal edema, a minor inflammatory response, and variable mucous
gland degeneration. Intranuclear inclusions were numerous in the affected
epidermis together with unique extracellular aggregates of herpesvirus-like
particles. The RHV3-associated skin disease has features similar to those of a
condition recognized in European frogs for the last 20 years and whose cause has
remained elusive. The genome of RHV3 shares most of the features of the
Alloherpesviruses. The characterization of this presumptive pathogen may be of
value for amphibian conservation and for a better understanding of the biology of
Alloherpesviruses.
PMID- 28494707
TI - Histologic and Ultrastructural Findings in Dogs With Chronic Respiratory Disease
Suspected of Ciliary Dyskinesia.
AB - Mucociliary clearance is a main defense mechanism of the respiratory tract, which
can be inherently impaired in primary ciliary dyskinesia (PCD) or reversibly
altered in secondary ciliary dyskinesia (SCD). Limited diagnostic test
availability likely leads to misdiagnosis or underdiagnosis of PCD in animals.
This study evaluated the light and transmission electron microscopy (TEM) changes
in the respiratory mucosa of 15 dogs with chronic respiratory disease suspected
of PCD. Necropsy was performed in 1 case and 2 dogs were used as negative
controls. PCD was confirmed in 1 dog, which presented with chronic otitis,
bronchopneumonia, hydrocephalus and ultrastructural abnormalities in 84% of the
assessed cilia, including absence of dynein arms and microtubular changes. The 14
other cases showed only nonspecific alterations, such as ciliary disorientation,
compound cilia, ciliary edema, and axoneme bubbles in a minority of the evaluated
cilia and were classified as SCD. Ciliary ultrastructural analysis can confirm a
diagnosis of PCD if specific abnormalities exist. TEM remains an important
investigational tool in veterinary medicine, as no other specific test for PCD in
dogs has been standardized yet.
PMID- 28494708
TI - Ovis aries Papillomavirus 3 in Ovine Cutaneous Squamous Cell Carcinoma.
AB - Squamous cell carcinoma (SCC) is a common malignancy affecting humans and other
animals. Papillomaviruses (PVs) are frequently reported as causal agents of
cutaneous benign and malignant epithelial lesions in different animal species,
but only few studies have investigated their role in ovine SCC. In this study, we
explore the possible involvement of the Ovine aries PVs (OaPV1, OaPV2, OaPV3) in
cutaneous SCC using an integrated histological and molecular approach. Forty
cutaneous SCCs from different anatomical locations of Sardinian sheep and 40
matched non-SCC samples were evaluated histologically and by polymerase chain
reaction (PCR) to assess the presence of ovine PVs. In addition, DNA in situ
hybridization (ISH) and reverse transcription-polymerase chain reaction (RT-PCR)
were carried out to evaluate the cellular localization and viral transcriptional
activity, respectively. OaPV3 DNA was detected in 26 of 40 (65%) SCCs and in 12
of 40 (30%) non-SCC samples using PCR. OaPV1 and OaPV2 were not detected. OaPV3
viral DNA was observed by ISH in malignant epithelial squamous cells of 18 of 40
(45%) SCCs. In addition, the viral transcriptional activity was identified in 24
of 40 (60%) SCCs by RT-PCR. Notably, a higher viral positivity was observed in
SCCs compared with non-SCC samples. The considerable infection rate of OaPV3 in
the most common skin tumor of the sheep suggests that PV could represent a key
factor in the onset of ovine SCC.
PMID- 28494709
TI - Hypervirulent Klebsiella pneumoniae in California Sea Lions ( Zalophus
californianus): Pathologic Findings in Natural Infections.
AB - Tissues of stranded California sea lions ( Zalophus californianus) naturally
infected with a hyperviruluent strain of Klebsiella pneumoniae were examined by
histopathology and immunohistochemistry against the K. pneumoniae K2 capsular
antigen. In 7 of 8 animals, there was severe purulent bronchopneumonia, sometimes
complicated by fibrinonecrotizing pleuritis with pyothorax. In affected areas of
lung, large numbers of degenerate neutrophils and macrophages were admixed with
rare large extracellular and intracellular gram-negative bacilli surrounded by a
prominent capsule. Through serotyping, polymerase chain reaction, sequencing, and
immunohistochemistry, these bacteria were confirmed to be a K2 serotype of K.
pneumoniae. The same bacteria were identified through double immunolabeling
within macrophages in blood vessels, lymph nodes, spleen, and liver. Intact K.
pneumoniae were identified on epithelial surfaces of the nasopharyngeal,
tracheal, and small intestine mucosae and within distal renal tubules. Our
findings indicate that hypervirulent K. pneumoniae causes severe respiratory
disease and intrahistiocytic bacteremia in California sea lions.
PMID- 28494711
TI - Abstracts to be presented at the 28th Annual Scientific Sessions.
PMID- 28494712
TI - Membership spotlight.
PMID- 28494710
TI - 2016 AHA/ACC Guideline on the Management of Patients with Lower Extremity
Peripheral Artery Disease: Executive Summary.
PMID- 28494713
TI - Vascular complications associated with transcatheter aortic valve replacement.
AB - Transcatheter aortic valve replacement (TAVR) is now an accepted pathway for
aortic valve replacement for patients who are at prohibitive, severe and
intermediate risk for traditional aortic valve surgery. However, with this rising
uptrend and adaptation of this new technology, vascular complications and their
management remain an Achilles heel for percutaneous aortic valve replacement. The
vascular complications are an independent predictor of mortality for patients
undergoing TAVR. Early recognition of these complications and appropriate
management is paramount. In this article, we review the most commonly encountered
vascular complications associated with currently approved TAVR devices and their
optimal percutaneous management techniques.
PMID- 28494714
TI - Is the Hepatic Factor a miRNA that Maintains the Integrity of Pulmonary
Microvasculature by Inhibiting the Vascular Endothelial Growth Factor?
AB - BACKGROUND: The "hepatic factor," a molecule or group of molecules present in the
hepatic venous blood, essential for the prevention of the development of
pulmonary arteriovenous malformations (PAVMs) and right-to-left shunting has been
a conceptual enigma in the understanding of many related conditions. METHODS:
Patients with various forms of liver diseases including acute hepatic failure,
and others with normal hepatic function like hereditary hemorrhagic
telangiectasia (HHT), inflammatory and parasitic disorders, cardiogenic
hepatopulmonary syndrome (cHPS) and skin disorders like Dyskeratosis congenita
are all known to cause PAVMs. Over a period of the last two decades our
understanding of the pathogenesis of PAVMs has changed, but the mechanisms are
still not clearly understood. The presence of PAVMs once considered a
contraindication for liver transplantation is now a cure for PAVMs in patients
with HPS. RESULTS: In this article the molecular mechanisms and the underlying
pathogenesis of PAVMs are discussed and the role of microRNA (miRNA) in its
pathogenesis is favorably argued. Identifying and preventing or treating the
underlying mechanisms will significantly influence the management of a large
group of patients who at present cannot be effectively treated with a very poor
prognosis. Progressive polycythemia, desaturation, stroke, and infection are
serious complications of PAVMs. CONCLUSION: The clinical data and current
understanding leads to the possible role of miRNA, which inhibits Vascular
Endothelial Growth Factor (VEGF) synthesis as a pathogenic mechanism for the
development of PAVMs.
PMID- 28494715
TI - The Click Test: A Novel Tool to Quantify the Age-Related Decline of Fast Motor
Sequencing of the Thumb.
AB - BACKGROUND: The thumb plays a critical role for manual tasks during the
activities of daily life and the incidence of neurological or musculoskeletal
disorders affecting the voluntary movements of the thumb is high in the elderly.
There is currently no tool to assess repetitive motor sequencing of the thumb
during ageing. OBJECTIVES: To report a novel procedure (the Click Test) assessing
the effects of ageing on fast motor sequencing of the thumb. METHOD: Healthy
subjects (n = 252; mean age +/- SD: 49.76 +/- 19.97 years; range: 19-89 years;
F/M: 151/101) were asked to perform fast repeated flexion/extension movements of
the thumb using a mechanical counter. RESULTS: Motor performances (assessed by
the number of clicks during 3 time periods: 15, 30 and 45 sec), significantly
decreased as a function of age for both the dominant (age effect; p< 0.0001 for
15, 30 and 45 sec) and the non-dominant hand (p<0.0001 for 15, 30 and 45 sec).
The number of clicks was significantly higher in males (gender effect; p<0.001)
and was higher on the dominant side as compared to the non-dominant side
(handedness effect: p<0.001). The Click Test is characterized by high
repeatability (coefficients of variation from 3.20 to 4.47%), excellent intra
rater reliability (intra-class coefficients ICC ranging from 0.89 to 0.98), high
inter-rater reproducibility (Pearson's product correlation ranging from 0.85 to
0.96), high internal consistency (Cronbach alpha coefficient=0.95) and is highly
correlated in terms of relative performances with the box and block test and the
9-hole peg test (positive linear correlation with the results of the box and
block test: p<0.001 for 15, 30 and 45 sec for both the dominant and the non
dominant hand; negative linear correlation with the results of the 9-hole peg
test: p<0.001 for 15, 30 and 45 sec for both the dominant and the non-dominant
hand). CONCLUSION: The Click Test is an entirely novel and very low cost tool to
reliably discriminate the ageing effects upon the performances during fast
repetitive motor sequencing of the thumb. The potential clinical and research
applications for motor functions are multiple, especially in acute and chronic
neurological disorders affecting the thumb as well as in the field of
rheumatology and orthopedics.
PMID- 28494716
TI - Gender Medicine and Pharmacoeconomics: A Narrative Review of the International
Literature of the Last 5 Years. A Revision of Evidences about the Relationship
Between Gender and Economic Consumption in Health.
AB - INTRODUCTION: The influence of patient gender on the economic impact of health
care has increasingly been examined in the recent literature. Gender appears to
have an impact on healthcare resource consumption, due to possible differences in
the patient's response to a chosen therapeutic management strategy or to a
healthcare intervention. OBJECTIVE: The present work is aimed at collecting and
reviewing evidences about the relationship between gender and economic
consumption in health based on worldwide scientific literature published in the
last 5 years. METHOD: We conducted a narrative review of evidence from an initial
pool of 904 articles, selecting information about gender-specific economic impact
in any therapeutic area. RESULTS: After title, abstract and full text review, 111
articles were relevant to the paper scope. The reviewed studies seem to be
confirming that a difference exists between males and females in the economic
implications of healthcare management and that those differences are particularly
relevant for cardiovascular and metabolic pathologies. Preliminary evidence
suggests overall healthcare costs are slightly higher in females than males,
while some specific and non-quantitative items of resource consumption, such as
quality of prescriptions, might favour male patients. Results do not allow to
clearly claiming an overall cost shift towards males or females, since their
polarization varies depending on the considered cost item or event category.
CONCLUSION: Studies suggested the presence of a gender difference in overall
healthcare resource consumption and costs. Nevertheless, these aspects still lack
thorough examination in literature and further analyses would be required on
longer time periods.
PMID- 28494717
TI - Gelatin as Biomaterial for Tissue Engineering.
AB - Tissue engineering is considered one of the most important therapeutic strategies
of regenerative medicine. The main objective of these new technologies is the
development of substitutes made with biomaterials that are able to heal, repair
or regenerate injured or diseased tissues and organs. These constructs seek to
unlock the limited ability of human tissues and organs to regenerate. In this
review, we highlight the convenient intrinsic properties of gelatin for the
design and development of advanced systems for tissue engineering. Gelatin is a
natural origin protein derived from collagen hydrolysis. We outline herein a
state of the art of gelatin-based composites in order to overcome limitations of
this polymeric material and modulate the properties of the formulations. Control
release of bioactive molecules, formulations with conductive properties or
systems with improved mechanical properties can be obtained using gelatin
composites. Many studies have found that the use of calcium phosphate ceramics
and diverse synthetic polymers in combination with gelatin improve the mechanical
properties of the structures. On the other hand, polyaniline and carbon-based
nanosubstrates are interesting molecules to provide gelatin-based systems with
conductive properties, especially for cardiac and nerve tissue engineering.
Finally, this review provides an overview of the different types of gelatin-based
structures including nanoparticles, microparticles, 3D scaffolds, electrospun
nanofibers and in situ gelling formulations. Thanks to the significant progress
that has already been made, along with others that will be achieved in a near
future, the safe and effective clinical implementation of gelatin-based products
is expected to accelerate and expand shortly.
PMID- 28494718
TI - 'Osteoimmunology' Offers New Perspectives for the Treatment of Pathological Bone
Loss.
AB - New evidence of the interactions between the immune system and bone has
accumulated in bone diseases, including osteoporosis, periodontitis and
rheumatoid arthritis. A marked imbalance between bone resorption and formation is
central to the onset of pathological bone loss. Osteoimmunology has revealed that
the immune system, including T cells, B cells and inflammatory cytokines, is a
key regulator of both osteoclasts and osteoblasts. Th1 cells, which differentiate
from CD4+T cells, are thought to play a major function during bone loss.
Moreover, the correlated expression of Th1 cytokines (interleukin-12 (IL-12),
interferon-gamma (IFN-gamma)) and bone-resorbing cytokines (tumor necrosis factor
alpha (TNF-alpha), IL-1) also plays a key role during inflammatory induced bone
resorption. Furthermore, a relatively new member of the CD4+T cell family Th17
displays the ability to promote osteoclast activity. The effect of IFN-gamma and
IL-17 released by Th 17 cells on pre-osteoclast proliferation, differentiation
and apoptosis provides the preliminary basis for the immune mechanism of
pathological bone loss. The role of B cells in osteoimmunological interactions
has long been suspected based on findings of B cells as active regulators of the
RANK/RANKL/OPG axis. Pathological bone loss, including osteoporosis and human
immunodeficiency virus-associated bone loss, are related to the altered RANKL/OPG
through modified production by B cells, supporting this assumption. All of the
above evidence may provide new theoretical explanations for the relationship
between bone metabolism and the immune system as well as offer perspectives for
the prevention and treatment of pathological bone loss.
PMID- 28494720
TI - HLA-C Single Nucleotide Polymorphism Associated with Increased Viral Load Level
in HIV-1 Infected Individuals from Northeast Brazil.
AB - BACKGROUND: Genetic variations in Human leukocyte antigen C (HLA-C), Zinc ribbon
domain containing 1 (ZNRD1) and its antisense RNA (ZNRD1-AS1) genes are known to
influence the HIV-1 replication and disease progression. OBJECTIVE AND METHOD: We
evaluated the distribution of HLA-C (rs10484554, rs9264942) and ZNRD1 (rs8321)
and ZNRD1-AS1 (rs3869068), single nucleotide polymorphisms (SNPs) in 266 HIV-1
infected and 223 unexposed-uninfected individuals from Northeast Brazil and their
relation to HIV-1 infection, CD4 T cells count and viral load pre-treatment.
RESULTS: HLA-C SNPs were in Linkage Disequilibrium (D'=0.84), constituting four
possible haplotypes. Our results showed that HLA-C, ZNRD1 and ZNRD1-AS1 SNPs as
well as HLA-C haplotypes frequencies were not significantly different between HIV
1-infected and unexposed-uninfected individuals. In addition, we analyzed HLA-C
and ZNRD-1 and ZNRD1-AS1 SNPs considering CD4+ T cell counts and viral load
before the antiretroviral treatment. Individuals carrying HLA-C rs9264942 TT
genotype showed a significant increased level of HIV-1 viral load pre-treatment,
in comparison with individuals carrying the CC genotype (p-value = 0.0092).
Finally, we stratified our findings according to CCR5Delta32 allele presence
along with the studied SNPs: no statistically significant influence over viral
load pre-treatment has been found. CONCLUSION: The association between HLA-C
rs9264942 SNP and viral load prior treatment in an admixed population from North
East Brazil was in agreement with findings from previous studies obtained on
different ethnic groups; however more studies should be conducted in order to
clarify how HLA-C impair the HIV-1 replication.
PMID- 28494721
TI - m6A Modification and Implications for microRNAs.
AB - OBJECTIVE: RNA is chemically modified with over 100 distinct reactions. Among
these reactions, methylation is probably the most extensively studied
modification on the RNA molecule. Studies suggest methylation of Adenine residues
(m6A) to be widespread in the transcriptome with potentially important roles in
biological processes. METHOD: Here, we review recent literature on m6A
modification and potential implications for microRNA (miRNA) mediated gene
expression regulation. These implications involve miRNA biogenesis, mRNA-miRNA
interactions and m6A target selection. CONCLUSION: Understanding the extent and
functions of m6A is likely to improve our understanding of the complexities of
the transcriptome regulation in normal and in disease states.
PMID- 28494719
TI - Levodopa in Parkinson's Disease: Current Status and Future Developments.
AB - BACKGROUND: Ever since the pioneering reports in the 60s, L-3,4
Dioxyphenylalanine (levodopa) has represented the gold standard for the treatment
of Parkinson's Disease (PD). However, long-term levodopa (LD) treatment is
frequently associated with fluctuations in motor response with serious impact on
patient quality of life. The pharmacokinetic and pharmacodynamic properties of LD
are pivotal to such motor fluctuations: discontinuous drug delivery, short half
life, poor bioavailability, and narrow therapeutic window are all crucial for
such fluctuations. During the last 60 years, several attempts have been made to
improve LD treatment and avoid long-term complications. METHODS: Research and
trials to improve the LD pharmacokinetic since 1960s are reviewed, summarizing
the progressive improvements of LD treatment. RESULTS: Inhibitors of peripheral
amino acid decarboxylase (AADC) have been introduced to achieve proper LD
concentration in the central nervous system reducing systemic adverse events.
Inhibitors of catechol-O-methyltransferase (COMT) increased LD half-life and
bioavailability. Efforts are still being made to achieve a continuous
dopaminergic stimulation, with the combination of oral LD with an AADC inhibitor
and a COMT inhibitor, or the intra-duodenal water-based LD/ carbidopa gel.
Further approaches to enhance LD efficacy are focused on new non-oral
administration routes, including nasal, intra-duodenal, intrapulmonary (CVT-301)
and subcutaneous (ND0612), as well as on novel ER formulations, including IPX066,
which recently concluded phase III trial. CONCLUSION: New LD formulations, oral
compounds as well as routes have been tested in the last years, with two main
targets: achieve continuous dopaminergic stimulation and find an instant deliver
route for LD.
PMID- 28494722
TI - Adult Stem Cells and Hydrogels for Cartilage Regeneration.
AB - Cartilage tissue engineering is emerging as a therapeutic approach for the repair
and regeneration of cartilage tissue defects resulting from trauma and disease.
It is still essential to explore approaches that employ combinations of ideal
seed cells, biomaterials, and growth factors to repair defect areas because
cartilage lacks spontaneous regenerative capabilities and traditional treatments
do not fully satisfy clinical requirements. The purpose of this review is to
summarize key advances in this area with an emphasis on adult stem cells because
these cells possess a self-renewal ability and the potential for multi
directional differentiation when cultured under appropriate conditions, such as
chondrocyte differentiation to synthesize cartilage-specific matrix proteins.
Additionally, hydrogels and their synergistic action with growth factors to co
regulate cell behaviors and cartilage regeneration will be addressed. Hydrogels
are three-dimensional water-swollen networks that provide a unique
microenvironment to promote the chondrogenic phenotype by encapsulating cells as
a functional cartilage substitute in a defect area. Ultimately, this review
presents the prospect of combining adult stem cells, hydrogels, and growth
factors using interdisciplinary approaches that may lead to significant
breakthroughs in cartilage regeneration in the future.
PMID- 28494723
TI - Recent Advances in Vaccines Against Leishmania Based on Patent Applications.
AB - BACKGROUND: Leishmaniasis is caused by parasites of the genus Leishmania, and
represents a group of chronic diseases with an epidemiological and clinical
diversity. The disease is endemic in tropical regions, being found in 98
countries, affecting around 12 million people, with an estimated increase of 1.5
million per year. METHODS: The present review aims to analyze recent and most
important patents regarding development of vaccines to improve immunization
against leishmaniasis. For this purpose, the Web of Science - Derwent Innovations
Index was consulted. There is also a short description of the licensed vaccines
already on the market for commercialization, and a critical opinion on future
developments. RESULTS: The data herein presented comprises national and
international filings, thus considering the patent's country of origin, and can
be used an indicator of a country's technological development regarding a
specific field. Several types of vaccines against Leishmania were studied. The
main classes comprise: vaccines using live cells (virulent or attenuated); dead
cells; containing recombinant protein; using DNA of the parasite. United States
(74 patents) leads the ranking of patent applications for vaccines against
Leishmania, followed by Brazil (36 patents), which is an endemic region of
leishmaniasis with 20,000 human cases of cutaneous leishmaniasis and over 3,000
cases of visceral form. CONCLUSION: This review showed that there is still a lot
of space for development regarding the creation of a feasible, effective vaccine
against leishmaniasis. The scientific community appears to be taking steps in the
right direction, though.
PMID- 28494724
TI - C-type Lectin Receptor: Old Friend and New Player.
AB - During the last two decades, C-type lectin receptors (CLRs) have been
demonstrated to play key roles in initiating the host immune response against
fungal infection. It is well established that CLRs, such as Dectin-1, Dectin-2,
Dectin-3 and Mincle recognize the cell wall component from the infected
microorganisms by using their carbohydrate recognition domain (CRD). Upon
stimulation, CLRs induce multiple signal transduction cascades through their own
immunereceptor tyrosine-based activation motifs (ITAMs) or interacting with ITAM
containing adaptor proteins such as FcRgamma, which then lead to the activation
of nuclear factor kappa B (NF-kappaB) through Syk- and CARD9-dependent pathway.
Dissecting CLR signal cascades and their effects on host immune cells is
essential to understand the molecular mechanisms in regulating host antifungal
immunity. Recently, the activated CLRs including Dectin-1 and Dectin-2 are
reported to undergo lysome-mediated degradation by an E3 ubiquitin ligase CBL-b.
Moreover, structural analysis will help understand the molecular mechanism of
these CLRs and provide clues to rational design for effective anti-fungal drugs.
Overall, we summarize the current knowledge on activating and inhibitory CLRs and
discuss how to boost host immune system to fight against invasive fungal
infection.
PMID- 28494725
TI - Computational Methods for Predicting ncRNA-protein Interactions.
AB - BACKGROUND: RNA-protein interactions (RPIs) play an important role in many
cellular processes. In particular, noncoding RNA-protein interactions (ncRPIs)
are involved in various gene regulations and human complex diseases. High
throughput experiments have provided a large number of valuable information about
ncRPIs, but these experiments are expensive and timeconsuming. Therefore, some
computational approaches have been developed to predict ncRPIs efficiently and
effectively. METHODS: In this work, we will describe the recent advance of
predicting ncRPIs from the following aspects: i) the dataset construction; ii)
the sequence and structural feature representation, and iii) the machine learning
algorithm. RESULTS: The current methods have successfully predicted ncRPIs, but
most of them trained and tested on the small benchmark datasets derived from
ncRNA-protein complexes in PDB database. The generalization performance and
robust of these existing methods need to be further improved. CONCLUSION:
Concomitant with the large numbers of ncRPIs generated by high-throughput
technologies, three future directions for predicting ncRPIs with machine learning
should be paid attention. One direction is that how to effectively construct the
negative sample set. Another is the selection of novel and effective features
from the sequences and structures of ncRNAs and proteins. The third is the design
of powerful predictor.
PMID- 28494726
TI - Chlorella vulgaris Induces Apoptosis of Human Non-Small Cell Lung Carcinoma
(NSCLC) Cells.
AB - OBJECTIVE: Chlorella vulgaris (C. vulgaris), a unicellular green microalga, has
been widely used as a food supplement and reported to have antioxidant and
anticancer properties. The current study was designed to assess the cytotoxic,
apoptotic, and DNA-damaging effects of C. vulgaris growth factor (CGF), hot water
C. vulgaris extracts, inlung tumor A549 and NCI-H460 cell lines. METHODS: A549
cells, NCI-H460 cells, and normal human fibroblasts were treated with CGF at
various concentrations (0-300 MUg/ml) for 24 hr. The comet assay and gammaH2AX
assay showed DNA damage in A549 and NCI-H460 cells upon CGF exposure. Evaluation
of apoptosis by the TUNEL assay and DNA fragmentation analysis by agarose gel
electrophoresis showed that CGF induced apoptosis in A549 and NCI-H460 cells.
RESULTS: Chlorella vulgaris hot water extract induced apoptosis and DNA damage in
human lung carcinoma cells. CONCLUSION: CGF can thus be considered a potential
cytotoxic or genotoxic drug for treatment of lung carcinoma.
PMID- 28494727
TI - Expression of Toll-like Receptor 2 and Toll-like Receptor 4 in Tuberculous
Pleural Effusion.
AB - BACKGROUND: Toll-like receptor-2 (TLR2) and Toll-like receptor-4 (TLR4) have been
reported to play a crucial role in tuberculosis, however, little is known about
their expression in tuberculous pleuritis. OBJECTIVE: The goal of this work is to
explore the expressions of TLR2 and TLR4 in tuberculous pleuritis and their
predominant expressions on cells. METHODS: Levels of soluble TLR2 and TLR4 by
enzyme linked immunosorbent assay (ELISA) in 58 patients with tuberculous pleural
effusion (PE) and 43 patients with malignant PE were determined. The related
genes were analyzed by RT-PCR and the membrane expressions of TLR2 and TLR4 on
CD3+, CD14+, and CD19+ monocytes were assessed by using flow cytometry in 20 of
58 patients with tuberculous pleuritis. RESULTS: Our results showed that the
levels of ADA, IL-27 and IFN-gamma in tuberculous PE were obviously higher than
in malignant PE. Moreover, the concentrations of soluble TLR2 and soluble TLR4 in
PE were significantly higher than those in peripheral blood of the same patients,
as well as the levels of soluble TLR2 in tuberculous PE were significantly higher
than those in malignant effusions. Furthermore, the levels of TLR2, TLR4 and IFN
gamma mRNA expression were marked increased in the tuberculous PE when compared
with the correspondent serum. Importantly, we found that the predominant
expressions of TLR2 in monocyte were on CD19 B cells, and the predominant
expressions of TLR4 were on CD14 monocytes/macrophages. CONCLUSION: Our findings
provided the evidence of a role for TLRs expression in tuberculous PE.
PMID- 28494728
TI - Design of Ru-arene Complexes for Antitumor Drugs.
AB - Recently, a number of promising ruthenium complexes have been investigated as
anticancer drugs. Ru-arene complexes with [(eta6-arene)Ru(X)(Y)(Z)] type, which
exhibit a great structural variety, offer much potential in drug design. In this
review we provide an overview of the progress in the field of arene ruthenium
chemistry. We focus our attention particularly on the molecular structures and
the anticancer applications of the Ru-arene complexes. Recent developments in the
chemistry of arene ruthenium complexes will provide information for the
investigation of novel anticancer organometallic drugs.
PMID- 28494729
TI - Synthetic Methods of Quinoline Derivatives as Potent Anticancer Agents.
AB - BACKGROUND: On account of significant biological activities, quinoline
derivatives have drawn more attention to the synthesis and biological activities
in the search for new therapeutic agents. Several new synthetic approaches have
been implemented to derive new molecules from quinoline and all the synthesized
molecules showed effective anticancer activity. METHOD: Some molecules are
synthesized using quinolones as precursor reactant, which is another effective
product of quinoline, also showing significant activity against malignant tumors.
The presence of nitrogen in it and its ability to bind with enzymes like gyrase,
topoisomerase II and kinase have also proven it with antitumor activity.
CONCLUSION: This review encapsulates the recent advances in the synthesis and
anticancer activity of Quinoline derivatives.
PMID- 28494730
TI - Small Molecule Efflux Pump Inhibitors in Mycobacterium tuberculosis: A Rational
Drug Design Perspective.
AB - Drug resistance in Mycobacterium tuberculosis (M. tuberculosis) complicates
management of tuberculosis. Efflux pumps contribute to low level resistance and
acquisition of additional high level resistance mutations through sub-therapeutic
concentrations of intracellular antimycobacterials. Various efflux pump
inhibitors (EPIs) have been described for M. tuberculosis but little is known
regarding the mechanism of efflux inhibition. As knowledge relating to the
mechanism of action and drug target is central to the rational drug design of
safe and sufficiently selective EPIs, this review aims to examine recent
developments in the study of EPIs in M. tuberculosis from a rational drug
development perspective and to provide an overview to facilitate systematic
development of therapeutically effective EPIs. Review of literature points to a
reduction in cellular energy or direct binding to the efflux pump as likely
mechanisms for most EPIs described for M. tuberculosis. This review demonstrates
that, where a direct interaction with efflux pumps is expected, both molecular
structure and general physicochemical properties should be considered to
accurately predict efflux pump substrates and inhibitors. Non-competitive EPIs do
not necessarily demonstrate the same requirements as competitive inhibitors and
it is therefore essential to differentiate between competitive and non
competitive inhibition to accurately determine structure activity relationships
for efflux pump inhibition. It is also evident that there are various
similarities between inhibitors of prokaryotic and eukaryotic efflux pumps but,
depending on the specific chemical scaffolds under investigation, it may be
possible to design EPIs that are less prone to inhibition of human P
glycoprotein, thereby reducing side effects and drug-drug interactions.
PMID- 28494731
TI - Microwave Assisted Grafting of Gums and Extraction of Natural Materials.
AB - BACKGROUND: Microwave assisted modification of polymers has become an established
technique for modifying the functionality of polymers. Microwave irradiation
reduces reaction time as well as the use of toxic solvents with enhanced
sensitivity and yields of quality products. OBJECTIVE: In this review article
instrumentation and basic principles of microwave activation have been discussed.
Microwave assisted grafting of natural gums, characterization of grafted polymers
and their toxicological parameters have also been listed. Pharmaceutical
applications viz. drug release retardant, mucoahesion and tablet
superdisintegrant potential of microwave assisted gums has also been discussed.
CONCLUSION: An overview of microwave assisted extraction of plant based natural
materials has also been presented.
PMID- 28494732
TI - Pharmacokinetics of Botanical Drugs and Plant Extracts.
AB - BACKGROUND: Botanical drugs contain plant extracts, which are complex mixtures of
compounds. As with conventional drugs, it is necessary to validate their efficacy
and safety through preclinical and clinical studies. However, pharmacokinetic
studies for active constituents or characteristic markers in botanical drugs are
rare. OBJECTIVE: The objective of this review was to investigate the global state
of the art in pharmacokinetic studies of active ingredients present in plant
extracts and botanical drugs. A review of pharmacokinetics studies of chemical
constituents of plant extracts and botanical drugs was performed, with a total of
135 studies published between January 2004 and February 2015 available in
recognized scientific databases. Botanical preparations were mainly found in the
form of aqueous extracts of roots and rhizomes. The most widely studied species
was Salvia miltiorrhiza Bunge, and the compound most frequently used as a
pharmacokinetic marker was berberine. CONCLUSION: Most studies were performed
using the Sprague Dawley rat model, and the preparations were mainly administered
orally in a single dose. Quantification of plasma concentrations of
pharmacokinetic markers was performed mainly by liquid-liquid extraction,
followed by high performance liquid chromatography coupled to mass spectrometry
detector. In conclusion, in recent years there has been an increasing interest
among researchers worldwide in the study of pharmacokinetics of bioactive
compounds in botanical drugs and plant extracts, especially those from the
Traditional Chinese Medicine.
PMID- 28494733
TI - Phage-Mediated Gene Therapy.
AB - BACKGROUND: Bacteriophages (bacterial viruses) have long been under investigation
as vectors for gene therapy. Similar to other viral vectors, the phage coat
proteins have evolved over millions of years to protect the viral genome from
degradation post injection, offering protection for the valuable therapeutic
sequence. MATERIALS AND METHODS: However, what sets phage apart from other viral
gene delivery vectors is their safety for human use and the relative ease by
which foreign molecules can be expressed on the phage outer surface, enabling
highly targeted gene delivery. The latter property also makes phage a popular
choice for gene therapy target discovery through directed evolution. Although
promising, phage-mediated gene therapy faces several outstanding challenges, the
most notable being lower gene delivery efficiency compared to animal viruses,
vector stability, and nondesirable immune stimulation. RESULT: This review
presents a critical review of promises and challenges of employing phage as gene
delivery vehicles as well as an introduction to the concept of phage-based
microbiome therapy as the new frontier and perhaps the most promising application
of phage-based gene therapy.
PMID- 28494734
TI - Recent Advances in Skin Penetration Enhancers for Transdermal Gene and Drug
Delivery.
AB - There is a growing interest in transdermal delivery systems because of their
noninvasive, targeted, and on-demand delivery of gene and drugs. However,
efficient penetration of therapeutic compounds into the skin is still challenging
largely due to the impermeability of the outermost layer of the skin, known as
stratum corneum. Recently, there have been major research activities to enhance
the skin penetration depth of pharmacological agents. This article reviews recent
advances in the development of various strategies for skin penetration
enhancement. We show that approaches such as ultrasound waves, laser, and
microneedle patches have successfully been employed to physically disrupt the
stratum corneum structure for enhanced transdermal delivery. Rather than physical
approaches, several non-physical route have also been utilized for efficient
transdermal delivery across the skin barrier. Finally, we discuss some clinical
applications of transdermal delivery systems for gene and drug delivery. This
paper shows that transdermal delivery devices can potentially function for
diverse healthcare and medical applications while further investigations are
still necessary for more efficient skin penetration of gene and drugs.
PMID- 28494735
TI - Perspectives of Gene Therapies in Autosomal Dominant Polycystic Kidney Disease.
AB - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most
common inherited kidney disease in the clinic. The predominant clinical
manifestation is bilateral and progressive cysts formation in the kidneys,
impairs normal renal parenchyma, and ultimately leads to endstage renal disease
(ESRD). ADPKD is a heterogenic disease which is resulted from the mutations of
PKD1 or PKD2 genes which encode polycystin-1 (PC1) and -2 (PC2), thereby multiple
cell signaling pathways are involved. METHOD: Although causative genes and
aberrant signaling pathways have been investigated for decades, lack of effective
and less side-effect treatment for the disease still perplex vast clinicians.
Therefore, development of new therapeutic approaches for ADPKD is currently very
much desired. CONCLUSION: This review will center on pathogenesis of ADPKD, and
thereafter gene transfer will be discussed as potential treatment for the
disease. New therapeutic interventions will bring further hope to improve
prognosis of this incurable disease.
PMID- 28494736
TI - Smart Micro/Nano-robotic Systems for Gene Delivery.
AB - BACKGROUND: Small scale robotics have attracted growing attention for the
prospect of targeting and accessing cell-sized sites, necessary for high
precision biomedical applications and drug/gene delivery. The loss of controlled
gene therapy, inducing systemic side effects and reduced therapeutic efficiency,
can be settled utilizing these intelligent carriers. METHODS: Newly proposed
solutions for the main challenges of control, power supplying, gene release and
final carrier extraction/degradation have shifted these smart miniature robots to
the point of being employed for practical applications of transferring
oligonucleotides (pDNA, siRNA, mRNA, etc.) in near future. CONCLUSION: In this
paper, different scenarios and their endeavors to address the vital working
demands and steps, in particular, carrier attachment and release, cell
internalization, manipulation concerns as well as actuation systems are
discussed.This review highlights some promising experimental results showing
controlled gene release of robotic systems in comparison with current non
specific gene delivery methods.
PMID- 28494737
TI - Lipid Nanoparticles as Potential Gene Therapeutic Delivery Systems for Oral
Administration.
AB - BACKGROUND: Gene therapy has experimented an increasing attention in the last
decades, due to its enormous potential applications in the medical field. It can
be defined as the use of genes or genetic material (DNA, RNA, oligonucleotides)
to treat or prevent a disease state, generally a geneticbased one. APPLICATION:
Other applications, like treating viral, bacterial or parasite infections or
development of vaccines are gaining also interest. Efficient gene therapy is
mainly dependent on the ability of the highly labile genetic material to reach
the therapeutic target. For this purpose, different delivery systems have been
designed and extensively investigated. Nanoparticles offer a broad range of
possibilities in design, being prepared using biocompatible and biodegradable
excipients, being therefore generally considered as safe. CONCLUSION: Oral
delivery of the genetic material is also a great challenge, due to the complexity
of this specific biological barrier. Special attention to all the intrinsic
hazards for gene delivery due to the barrier must be taken into account during
the particle design process. Particle design will also allow targeting to
specific sites of the gastrointestinal tract. Solid lipid nanoparticles have been
extensively studied in the oral drug delivery field, and also in gene delivery
through other administration routes, but still not explored in oral gene
delivery. In this manuscript, design considerations and particle-cell interaction
mechanisms will be extensively reviewed, focusing on the oral route to encourage
the scientific community to explore these valuable carriers for oral gene
delivery.
PMID- 28494738
TI - Smart and Controllable rAAV Gene Delivery Carriers in Progenitor Cells for Human
Musculoskeletal Regenerative Medicine with a Focus on the Articular Cartilage.
AB - Cell therapy using mesenchymal stem cells (MSCs) is a powerful tool for the
treatment of various diseases and injuries. Still, important limitations
including the large amounts of cells required for application in vivo and the age
related decline in lifespan, proliferation, and potency may hinder the use of
MSCs in patients. In this regard, gene therapy may offer strong approaches to
optimize the use of MSCs for regenerative medicine. Diverse nonviral and viral
gene vehicles have been manipulated to genetically modify MSCs, among which the
highly effective and relatively safe recombinant adeno-associated viral (rAAV)
vectors that emerged as the preferred gene delivery system to treat human
disorders. Yet, clinical adaptation of such gene vehicles may be limited by
several hurdles, including the possibility of dissemination to nontarget sites
and the presence of immune and toxic responses in the host organism that may
impair their therapeutic actions. The use of smart biomaterials acting as
interfaces to enhance the temporal and spatial presentation of therapeutic agents
in the target place and/or acting as scaffolding for MSC growth is an innovative,
valuable approach to overcome these shortcomings that else restrain the efficacy
of such potent cell populations. Here, we provide an overview on the most recent
tissue engineering approaches based on the use of biomaterials acting as vehicles
for rAAV vectors to target MSCs directly in the recipient (in vivo strategy) or
as supportive matrices for rAAV-modified MSCs for indirect cell reimplantation
(ex vivo strategy) as means to activate the reparative processes in tissues of
the musculoskeletal system.
PMID- 28494739
TI - Gene Delivery Particle Engineering Strategies for Shape-dependent Targeting of
Cells and Tissues.
AB - BACKGROUND: Successful gene delivery requires overcoming both systemic and
intracellular obstacles before the nucleic acid cargo can successfully reach its
tissue and subcellular target location. Materials & Methods: Non-viral mechanisms
to enable targeting while avoiding off-target delivery have arisen via
biological, chemical, and physical engineering strategies. DISCUSSION: Herein we
will discuss the physical parameters in particle design that promote tissue- and
cell-targeted delivery of genetic cargo. We will discuss systemic concerns, such
as circulation, tissue localization, and clearance, as well as cell-scale
obstacles, such as cellular uptake and nucleic acid packaging. CONCLUSION: In
particular, we will focus on engineering particle shape and size in order to
enhance delivery and promote precise targeting. We will also address methods to
program or change particle shape in situ using environmentally triggered cues.
PMID- 28494740
TI - Nucleic Acids-based Nanotherapeutics Crossing the Blood Brain Barrier.
AB - The restless endeavors revealing the molecular pathways underlying many
neurodegenerative diseases and brain tumors have paved the way for the
introduction of the selective exogenous gene-based therapeutics. The implicated
active biomolecules encompass mainly negatively-charged nucleic acids ranging
from DNA, mRNA, non-coding RNAs (small-interfering RNA, siRNA, and microRNA,
miRNA), to antisense oligonucleotides. They selectively interfere with the genes
translational and/or transcriptional processes. Although many reviews previously
addressed brain targeting, a thorough correlation between the molecular
properties of these biomacromolecules, the nature of blood brain barrier (BBB) in
the accompanying pathological condition, the intracellular targets, as well as
the design of the delivery system which will transport the bioactive cargo to the
target cells attempting efficient delivery to the active sites in the brain will
be appraised. In this review, we will further discuss the tremendous advances in
non-viral gene delivery nanosystems currently investigated (starting from self
assembled nanoplexes using cationic polymers or lipids and going through
liposomes, aptamers, polymersomes, exosomes, dendrimers and nanoparticles).
Unlike previous reviews on this topic, functionalization strategies of the
nanocarriers promoting either surface receptor binding or intracellular targeting
of the cranial cells will be highlighted, with special emphasis on tailoring
smart nanomedicines according to the CNS disease condition. In addition, newly
developed evaluation approaches, cell culture models studying BBB permeability
and manipulation of the barrier function of the brain via focused ultrasound will
be addressed.
PMID- 28494741
TI - Delivering siRNA with Dendrimers: In Vivo Applications.
AB - Over the last decades, gene therapy has emerged as a pioneering therapeutic
approach to treat or prevent several diseases. Among the explored strategies, the
short-term silencing of protein coding genes mediated by siRNAs has a good
therapeutic potential in a clinical setting. However, the widespread use of siRNA
will require the development of clinically suitable, safe and effective vehicles
with the ability to complex and deliver siRNA into target cells with minimal
toxicity. Lately, dendrimers have gained considerable attention as non-viral
vectors in nucleic acid delivery due to their unique structural characteristics
(globular, well defined and highly branched structure, multivalency, low
polydispersity and tunable nanosize), along with their relevant capacity to
complex and protect nucleic acids in compact nanostructures, which can be
functionalized with targeting moieties in order to get cell specificity. Here, we
present an overview of the state-of-the-art of the most significant and recent
advances on the use of dendrimers as siRNA delivery vectors, with particular
focus on the in vivo applications. We will cover the use of different dendrimers,
distinct administration routes, toxicity issues, as well as the target tissue or
disease, highlighting the potential of dendrimers as nanocarriers for therapeutic
and biomedical applications.
PMID- 28494742
TI - Potential Gene Therapy Towards Treating Neurodegenerative Disea ses Employing
Polymeric Nanosystems.
AB - BACKGROUND: Recent integrated approaches involving nanotechnology and gene
therapy have accelerated development of efficient drug delivery to the central
nervous system (CNS). Neurodegenerative disorders are closely associated with
genetic inheritance and mutation. MATERIALS: Nanotechnology has allowed effective
engineering of various such polymeric structures. Moreover, availability of a
wide array of polymeric materials has enabled fabrication of biocompatible and
biodegradable delivery vehicles. Our manuscript focuses on the ideal features and
properties of polymeric nanoparticles that have enabled successful gene therapy
for neurodegenerative disorders, as well as the challenges that are posing
difficulties in their practical application. We have highlighted these aspects
through examples of polymeric nanoparticles that have exhibited therapeutic
promise in the treatment of neurological disorders and mutations. METHODS:
Complete cure of these diseases is a challenging task and gene therapy appears as
a realistic approach for their treatment. Gene therapy allows effective
replacement or suppression of faulty genes, thereby increasing chances for neuron
survival and repair. However, successful delivery of naked genetic material to
CNS faces severe obstacles due to possible degradation and restricted
transportation of these biological entities across the blood brain barrier (BBB).
Structurally, the BBB is composed of several tight junctions, making the membrane
highly selective towards the entry of molecules. CONCLUSION: In order to target
BBB for treating neurodegenerative diseases, it is essential to develop a tailor
made system that may not only cross this barrier, but also effectively modulate
the expression of disease-causing genes. Stabilization of therapeutic genes and
their effective, targeted delivery may be possible using polymeric nanoparticles
as carriers.
PMID- 28494743
TI - Osteonecrosis of the Jaw and Angiogenesis inhibitors: A Revival of a Rare but
Serous Side Effect.
AB - Osteonecrosis of the jaw (ONJ) is a rare treatment related side effect that was
firstly described in 2002 through a case report in metastatic bone cancer patient
treated with bisphosphonates (BPs) therapy. ONJ is defined as an eight weeks or
longer clinical finding of exposed bone in the oral cavity without response to
appropriate therapy. The diagnosis is mainly clinical but often requires a
radiological confirmation with an orthopantomography. So it must be made by a
dental specialist with sufficient experience on ONJ and requires a detailed
anamnestic exploration of comorbidities and treatments history. In particular,
ONJ affects a wide number of oncologic patients treated with BPs for bone
metastatic cancers and, more recently, with anti-angiogenic drugs. The aim of
this this paper is to describe diagnosis and classification of this rare but
serious side effect and its pathophysiology. In particular, we provide a detailed
description of clinical evidences upon the relationship between anti-angiogenic
drugs and ONJ. Considering the evolving of cancer epidemiology with a greater
number of cancer surviving patients, this side effect always deserves more
attention. We conclude that ONJ must be always carefully investigated and
prevented with a multidisciplinary approach involving oncologist, radiation
oncologist and skilled dental practitioner when a cancer patient must begin a BP
or an antiangiogenic treatment.
PMID- 28494744
TI - Targeting Nrf2 in Protection Against Renal Disease.
AB - BACKGROUND: Renal disease is a serious health problem, with increasing incidence
and prevalence. Oxidative stress and inflammation play a key role in the
pathogenesis and progression of renal disease. Therefore, therapeutic approaches
to decrease oxidative stress should be of interest. OBJECTIVE: This review aims
to provide a comprehensive and updated overview of the protective mechanisms
mediated by Nrf2 (nuclear factor erythroid 2-related factor 2), a description of
novel compounds that target Nrf2, its effectiveness to prevent renal disease and
the on-going clinical trials for this pathological condition. METHODS: We
undertook a structured search of bibliographic databases for peer-reviewed
research in literature about Nrf2 activators and renal disease. RESULTS: The
transcription factor Nrf2 is an emerging regulator of cellular resistance to
oxidants and inflammation. Nrf2 controls the basal and induced expression of a
couple of cytoprotective and antiinflammatory genes that regulate the
physiological and pathophysiological outcomes of oxidant exposure. We have
analyzed numerous findings showing that Nrf2 induction protects against oxidative
stress and modulates inflammation in acute kidney injury and chronic kidney
disease progression. However, few clinical trials have been performed in humans.
Recent studies suggested that renoprotective effects of Nrf2 activation are
observed at low doses, whereas harmful effects appear at higher concentrations.
CONCLUSION: The findings of this review confirm that novel studies are necessary
to address whether Nrf2-targeting may be a safe therapeutic approach to decrease
renal disease progression in humans.
PMID- 28494745
TI - Global View on Rare Diseases: A Mini Review.
AB - BACKGROUND: Rare diseases are often serious, life-threatening and debilitating
group of disorders. Nowadays, there are approximately 8,000 rare diseases and it
is estimated that 350 million people are affected by these conditions worldwide.
Unfortunately, rare diseases are quite complex and chronic, only a small number
of these diseases can be relevantly diagnosed and treated, and lifelong treatment
is often required. OBJECTIVE: The purpose of this mini review is to explore the
issue of rare diseases, describe their classification, discuss the current
treatment and management and set future research in this field. METHODS: The
methods applied in this review include literature review of the world's
acknowledged databases such as PubMed, Springer and Web of Science, especially in
the period of 2000 to 2015. Furthermore, a method of comparison and evaluation of
the findings from the relevant sources is used. RESULTS: The findings confirm
that rare diseases are still quite difficult to diagnose due to their
comorbidities. Once they are diagnosed, they demand costly and long-term
treatment, which raises concerns of national governments. CONCLUSION: Therefore
more research should be done in the space of rare diseases in order to broaden
knowledge about them, their diagnosis and treatment, which will then lead to
better training of medical staff, and ultimately will benefit the patients.
PMID- 28494746
TI - Fungal Anticancer Metabolites: Synthesis Towards Drug Discovery.
AB - BACKGROUND: Fungi are a well-known and valuable source of compounds of
therapeutic relevance, in particular of novel anticancer compounds. Although
seldom obtainable through isolation from the natural source, the total organic
synthesis still remains one of the most efficient alternatives to resupply them.
Furthermore, natural product total synthesis is a valuable tool not only for
discovery of new complex biologically active compounds but also for the
development of innovative methodologies in enantioselective organic synthesis.
METHODS: We undertook an in-depth literature searching by using chemical
bibliographic databases (SciFinder, Reaxys) in order to have a comprehensive
insight into the wide research field. The literature has been then screened,
refining the obtained results by subject terms focused on both biological
activity and innovative synthetic procedures. RESULTS: The literature on fungal
metabolites has been recently reviewed and these publications have been used as a
base from which we consider the synthetic feasibility of the most promising
compounds, in terms of anticancer properties and drug development. In this paper,
compounds are classified according to their chemical structure. CONCLUSION: This
review summarizes the anticancer potential of fungal metabolites, highlighting
the role of total synthesis outlining the feasibility of innovative synthetic
procedures that facilitate the development of fungal metabolites into drugs that
may become a real future perspective. To our knowledge, this review is the first
effort to deal with the total synthesis of these active fungi metabolites and
demonstrates that total chemical synthesis is a fruitful means of yielding fungal
derivatives as aided by recent technological and innovative advancements.
PMID- 28494747
TI - New Diagnostic and Therapeutic Aspects of Pancreatic Ductal Adenocarcinoma.
AB - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is devastating. Because of
its silent nature, the disease is often only diagnosed once it has reached an
advanced, frequently inoperable stage. To date, we have no biomarkers that
facilitate earlier diagnosis, leaving sufficient time for curative therapy that
effectively lowers the very high mortality rate of this cancer entity. Because of
this, the life expectancy of patients with PDAC is low (i.e. <= 6% five-year
survival rates). New data, including particular genetic signatures and features
of the stromal architecture of PDAC tumors, may better explain their
aggressiveness, their relatively long-lasting painless expansion, and why
chemotherapy so frequently fails. The typical tumor-induced stromal desmoplasia
is characterized by cancer-associated fibroblasts (CAFs), decreased immune
surveillance, cancer-associated neural remodeling, and a very low vascular
density. This stromal microenvironment generates hypoxia, nutrient deficiency,
immune suppression, and chemoresistance. The combination of factors results in a
vicious disease that begins with the long-lasting, asymptomatic development of a
large tumor mass, followed by a delayed diagnosis with a high percentage of
inoperable states, exhibiting a poor response to all conservative therapeutic
options, including radiation, and which ends with metastasis resulting in a rapid
fatal outcome. OBJECTIVE: In this article, we review coherences on genetic,
cellular, immunological, Nano medical and stromal characteristics of PDAC tissue,
and discuss metabolic abnormalities associated with and/or preceding the tumor
progression rate. CONCLUSION: A more comprehensive understanding of the
underlying mechanisms can improve the diagnostic and therapeutic management of
patients suffering from this devastating type of cancer.
PMID- 28494748
TI - The novelty of bupropion as a dopaminergic antidepressant for the treatment of
adult attention deficit hyperactive disorder.
AB - Attention deficit hyperactive disorder (ADHD), a hyperactivity disorder that is
prevalent among children may continue as an adulthood attention deficit. To date,
treating an individual with an adult ADHD may be an arduous task as it involved
numerous challenges, such as a need for high index of suspicion to diagnose this
medical condition. Many psychiatric disorders masquerade as ADHD and delayed the
necessary assessment and proper treatment for the debilitating medical condition.
Adult ADHD would also be misdiagnosed (or under diagnosed) due to the facts that
this medical condition is being masked by his or her high level of
intellectuality achievement. As the ADHD in adult persisted, it may end-up with
impairment in the personal-social-occupational function, in which the management
became a great challenge. The treatment of ADHD can be optimized by using various
drugs targets agents like a norepinephrine-dopamine reuptake inhibitor (NDRI),
with or without psycho stimulants like methylphenidate, which was marketed as
ritalin. Bupropion, a NDRI has a novel effect on ADHD as the molecule exerts its
effects by modulating the reward-pleasure mesolimbic dopaminergic system, and at
the same time regulating the elevating mood dimension of the noradrenergic
neurotransmission. The role of bupropion in the neural and psychopharmacological
perspective treatment of ADHD was deliberated. This review highlights the novelty
effects of bupropion in treating ADHD, together with the help of other successful
bio-psycho-social measures, which may offer a great assistance to the
psychiatrists in treating their patients to the level best.
PMID- 28494749
TI - Alcohol Addiction- Metabotropic Glutamate Receptor Subtype 5 and its Ligands: How
They All Come Together?
AB - In the past decade, many studies have highlighted the role of metabotropic
glutamate receptor subtype 5 (mGlu5) modulators in attenuating alcohol-related
biological effects such as alcohol consumption, alcohol-seeking and relapse-like
behaviors. Taken together, these findings suggest that pharmacological agents
acting at mGlu5 could be promising tools in curbing inebriation. mGlu5s are
present abundantly in brain regions known to be involved in emotion regulation,
motivation and drug administration. On a cellular level, they are primarily
located at the postsynaptic part of the neuron where the receptor is functionally
linked to various downstream proteins that are involved in cell signaling and
gene transcription that mediate the alcohol-induced neuroplasticity. As well, the
discovery of a functional link between mGlu5 and a specific isozyme, Protein
Kinase C epsilon (PKCepsilon) in mediating the attenuating effects of selective
negative allosteric modulators of mGlu5 such as methyl- 6(phenylethynyl)pyridine
(MPEP) and 3-((2-methyl-4-thiazolyl)ethynyl)pyridine (MTEP) has sparked
interesting speculations. In this article, we shall review the following: the
effects of acute and chronic alcohol intake on mGlu5 signaling; the effects of
mGlu5 ligands on alcohol-related neurobehavioral changes that are currently being
studied both at pre-clinical and clinical stages; and the mechanisms underlying
the pharmacological effects of these drugs.
PMID- 28494750
TI - Direct and indirect risk associated with the use of dietary supplements among
persons with dementia in a Norwegian memory clinic.
AB - BACKGROUND: The use of dietary supplements (DS) is common among persons with
dementia. Direct risks associated with DS use include adverse events and DS-drug
interactions. A direct risk is a risk caused by the treatment itself. Indirect
risks are related to the treatment setting, such as the conditions of use, and
not to the treatment itself. Because dementia symptoms may reduce a person's
ability to cope with the administration of DS, the use of DS may pose a threat to
safety as an indirect risk. The aim of this study was to describe the extent of
DS use among persons with dementia in ambulatory care and to identify some
relevant direct and indirect risks related to DS use. METHODS: We conducted a
survey among 151 persons with dementia attending an outpatient memory clinic in
Northern Norway. Study measurements included: the participants' characteristics,
cognitive functioning, functioning in the activities of daily living (ADL), and
the use of DS and prescription drugs (PD). We assessed direct risks by evaluating
potential DS-drug interactions and indirect risks by evaluating the conditions
under which it was used. RESULTS: Forty-six percent (n = 70) of the persons with
dementia used DS. Ninety-seven percent (n = 147) used PD. We found potentially
clinically relevant DS-drug interactions representing a direct risk in eight
persons with dementia (11% of users). While only 36% (n = 26) of the participants
received assistance with the administration of DS, 73% (n = 106) received
assistance with the administration of PD. Persons with dementia living alone were
at risk of not receiving assistance, as home care service seldom was involved in
DS administration. Data indicated that assistance with DS administration was not
provided for all persons with dementia in need, representing an indirect risk to
these persons. Only one-third of the persons with dementia and half of the
caregivers were aware of the general risks of adverse events and interactions
associated with the use of DS. CONCLUSIONS: Persons with dementia use DS
frequently, yet DS use may be associated with direct and indirect risks to
patient safety as potentially clinically relevant interactions were discovered
and DS intake often was unsupervised.
PMID- 28494751
TI - Integrated analysis of droxidopa trials for neurogenic orthostatic hypotension.
AB - BACKGROUND: Droxidopa, a prodrug of norepinephrine, was approved for treatment of
neurogenic orthostatic hypotension (nOH) due to primary autonomic disorders based
on 3 randomized double-blind studies. We performed safety and efficacy analyses
of this pooled dataset (n = 460). METHODS: Efficacy was assessed using
Orthostatic Hypotension Questionnaire (OHQ) scores (composite and individual
items). Safety and tolerability were also examined. RESULTS: Droxidopa improved
virtually all nOH symptom scores compared with placebo, significantly reducing
OHQ composite score (-2.68 +/- 2.20 vs -1.82 +/- 2.34 units; P < 0.001),
dizziness/lightheadedness score (-3.0 +/- 2.9 vs -1.8 +/- 3.1 units; P < 0.001),
and 3 of 5 other symptom assessments (visual disturbances, weakness, and fatigue
[P <= 0.010]). Droxidopa significantly improved 3 of 4 measures of activities of
daily living (standing a long time, walking a short time, and walking a long time
[P <= 0.003]) and significantly increased upright systolic blood pressure (11.5
+/- 20.5 vs 4.8 +/- 21.0 mmHg for placebo; P < 0.001). Droxidopa was effective in
patients using inhibitors of dopa decarboxylase (DDCI; the enzyme that converts
droxidopa to norepinephrine), but its efficacy was numerically greater in non
DDCI users. Droxidopa was well-tolerated. Rates of most adverse events were
similar between groups. Supine hypertension rates were low, but slightly higher
in patients receiving droxidopa (<=7.9% vs <=4.6% for placebo); patients with
severe hypertension at screening were excluded from these studies. CONCLUSIONS:
Droxidopa is effective for the treatment of nOH in patients with primary
autonomic disorders and is generally well-tolerated. A longer trial is underway
to confirm efficacy beyond the <=2 to 10 - week period assessed in the current
trials. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT00782340 , first
received October 29, 2008; NCT00633880 , first received March 5, 2008; and
NCT01176240 , first received July 30, 2010.
PMID- 28494752
TI - MDA-MET-conditioned-medium augments the chemoattractant-dependent migration of
MDA-MET cells towards hFOB-conditioned medium and increases collagenase activity.
AB - BACKGROUND: Metastasis of breast cancer displays site-specificity towards bone.
Recently, studies have emerged indicating that primary tumors may remotely
influence creation of a pre-metastatic niche. In this study, we used human fetal
osteoblastic cells and MDA-MET, a metastatic and preferentially bone homing
derivative of the breast cancer cell line MDA-MB-231. We examined 1) whether
secreted factors from MDA-MET cells increase generation of chemoattractants by
human foetal osteoblastic cells 2) whether MDA-MET cells were responsive to these
chemoattractants and 3) the identity of these chemoattractants. METHODS: Human
foetal osteoblastic cells were treated with conditioned medium of MDA-MET cells
for 24 hours and then washed with phosphate-buffered saline. Serum-free
replacement medium was conditioned by treated hFOB cells for 18 hours, before its
use in in vitro quantification of MDA-MET migration. We also quantified collagen
levels and collagenase activity in conditioned medium from human foetal
osteoblastic cells. RESULTS: Conditioned medium from human foetal osteoblastic
cells that had been treated with MDA-MET-conditioned medium attracted more MDA
MET cells than hFOB cells pre-exposed to their own medium. This conditioned
medium had increased collagenase activity. The addition of bacterial collagenase
removed the ability of conditioned medium from human foetal osteoblastic cells to
attract MDA-MET cells. CONCLUSIONS: Our data suggest that an increase in
collagenase activity in osteoblastic cells induced by their exposure to breast
cancer cell-secreted factors may increase their ability to attract breast cancer
cells.
PMID- 28494753
TI - Preventing sickness absenteeism among employees with common mental disorders or
stress-related symptoms at work: Design of a cluster randomized controlled trial
of a problem-solving based intervention versus care-as-usual conducted at the
Occupational Health Services.
AB - BACKGROUND: Common mental disorders (CMDs) are among the leading causes of sick
leave in Sweden and other OECD countries. They result in suffering for the
individual and considerable financial costs for the employer and for society at
large. The occupational health service (OHS) can offer interventions in which
both the individual and the work situation are taken into account. The aim of
this paper is to describe the design of a study evaluating the effectiveness of
an intervention given at the OHS to employees with CMDs or stress-related
symptoms at work. In addition, intervention fidelity and its relation to the
outcome will be assessed in a process analysis. METHODS: The study is designed as
a cluster randomized trial in which the participating OHS consultants are
randomized into either delivering the intervention or performing care as usual.
Employees with CMDs or stress-related symptoms at work are recruited
consecutively by the OHS consultants. The intervention aims to improve the match
between the employee and the job situation. Interviews are held individually with
the employee and the nearest supervisor, after which a joint meeting with both
the employee and the supervisor takes place. A participatory approach is applied
by which the supervisor and the employee are guided by the OHS consultant and
encouraged to actively take part in problem solving concerning the work
situation. Outcomes will be assessed at baseline and at six and 12 months. A long
term follow-up at 3 years will also be performed. The primary outcome is
registered sickness absence during a 1-year period after study inclusion.
Secondary outcomes are mental health and work ability. The intervention's cost
effectiveness, compared to treatment as usual, both for society and for the
employer will be evaluated. A process evaluation by both the OHS consultants and
the employee will be carried out. DISCUSSION: The study includes analyses of the
effectiveness of the intervention (clinical and economic) as well as an analysis
of its implementation at the participating OHSs. Possible methodological
challenges such as selection bias and risk of contamination between OHS
consultants delivering the experimental condition and consultants giving usual
care are discussed. TRIAL REGISTRATION: ClinicalTrials NCT02563743 Sep 28 2015.
PMID- 28494754
TI - Circulating cathelicidin levels correlate with mucosal disease activity in
ulcerative colitis, risk of intestinal stricture in Crohn's disease, and clinical
prognosis in inflammatory bowel disease.
AB - BACKGROUND: Cathelicidin (LL-37) is an antimicrobial peptide known to be
associated with various autoimmune diseases. We attempt to determine if
cathelicidin can accurately reflect IBD disease activity. We hypothesize that
serum cathelicidin correlates with mucosal disease activity, stricture, and
clinical prognosis of IBD patients. METHODS: Serum samples were collected from
two separate cohorts of patients at the University of California, Los Angeles.
Cohort 1 consisted of 50 control, 23 UC, and 28 CD patients. Cohort 2 consisted
of 20 control, 57 UC, and 67 CD patients. LL-37 levels were determined by ELISA.
Data from both cohorts were combined for calculation of accuracies in indicating
mucosal disease activity, relative risks of stricture, and odds ratios of
predicting disease development. RESULTS: Serum cathelicidin levels were inversely
correlated with Partial Mayo Scores of UC patients and Harvey-Bradshaw Indices of
CD patients. Among IBD patients with moderate or severe initial disease activity,
the patients with high initial LL-37 levels had significantly better recovery
than the patients with low initial LL-37 levels after 6-18 months, suggesting
that high LL-37 levels correlate with good prognosis. Co-evaluation of LL-37 and
CRP levels was more accurate than CRP alone or LL-37 alone in the correlation
with Mayo Endoscopic Score of UC patients. Low LL-37 levels indicated a
significantly elevated risk of intestinal stricture in CD patients. CONCLUSION:
Co-evaluation of LL-37 and CRP can indicate mucosal disease activity in UC
patients. LL-37 can predict future clinical activity in IBD patients and indicate
risk of intestinal stricture in CD patients.
PMID- 28494755
TI - Transcriptome analysis of the whitefly, Bemisia tabaci MEAM1 during feeding on
tomato infected with the crinivirus, Tomato chlorosis virus, identifies a
temporal shift in gene expression and differential regulation of novel orphan
genes.
AB - BACKGROUND: Whiteflies threaten agricultural crop production worldwide, are
polyphagous in nature, and transmit hundreds of plant viruses. Little is known
how whitefly gene expression is altered due to feeding on plants infected with a
semipersistently transmitted virus. Tomato chlorosis virus (ToCV; genus
Crinivirus, family Closteroviridae) is transmitted by the whitefly (Bemisia
tabaci) in a semipersistent manner and infects several globally important
agricultural and ornamental crops, including tomato. RESULTS: To determine
changes in global gene regulation in whiteflies after feeding on tomato plants
infected with a crinivirus (ToCV), comparative transcriptomic analysis was
performed using RNA-Seq on whitefly (Bemisia tabaci MEAM1) populations after 24,
48, and 72 h acquisition access periods on either ToCV-infected or uninfected
tomatoes. Significant differences in gene expression were detected between
whiteflies fed on ToCV-infected tomato and those fed on uninfected tomato among
the three feeding time periods: 447 up-regulated and 542 down-regulated at 24 h,
4 up-regulated and 7 down-regulated at 48 h, and 50 up-regulated and 160 down
regulated at 72 h. Analysis revealed differential regulation of genes associated
with metabolic pathways, signal transduction, transport and catabolism,
receptors, glucose transporters, alpha-glucosidases, and the uric acid pathway in
whiteflies fed on ToCV-infected tomatoes, as well as an abundance of
differentially regulated novel orphan genes. Results demonstrate for the first
time, a specific and temporally regulated response by the whitefly to feeding on
a host plant infected with a semipersistently transmitted virus, and advance the
understanding of the whitefly vector-virus interactions that facilitate virus
transmission. CONCLUSION: Whitefly transmission of semipersistent viruses is
believed to require specific interactions between the virus and its vector that
allow binding of virus particles to factors within whitefly mouthparts. Results
provide a broader understanding of the potential mechanism of crinivirus
transmission by whitefly, aid in discerning genes or loci in whitefly that
influence virus interactions or transmission, and subsequently facilitate
development of novel, genetics-based control methods against whitefly and
whitefly-transmitted viruses.
PMID- 28494756
TI - Solving the master equation for Indels.
AB - BACKGROUND: Despite the long-anticipated possibility of putting sequence
alignment on the same footing as statistical phylogenetics, theorists have
struggled to develop time-dependent evolutionary models for indels that are as
tractable as the analogous models for substitution events. MAIN TEXT: This paper
discusses progress in the area of insertion-deletion models, in view of recent
work by Ezawa (BMC Bioinformatics 17:304, 2016); (BMC Bioinformatics 17:397,
2016); (BMC Bioinformatics 17:457, 2016) on the calculation of time-dependent gap
length distributions in pairwise alignments, and current approaches for extending
these approaches from ancestor-descendant pairs to phylogenetic trees.
CONCLUSIONS: While approximations that use finite-state machines (Pair HMMs and
transducers) currently represent the most practical approach to problems such as
sequence alignment and phylogeny, more rigorous approaches that work directly
with the matrix exponential of the underlying continuous-time Markov chain also
show promise, especially in view of recent advances.
PMID- 28494757
TI - COPD monocytes demonstrate impaired migratory ability.
AB - BACKGROUND: Increased lung macrophage numbers in COPD may arise from upregulation
of blood monocyte recruitment into the lungs. CCR5 is a monocyte chemokine
receptor regulated by interleukin-6 (IL-6); the concentration of CCR5 ligands are
known to be elevated in COPD lungs. The objective of this study was to
investigate mechanisms of monocyte recruitment to the lung in COPD, including the
role of CCR5 signalling. METHODS: Ninety one COPD patients, 29 smokers (S) and 37
non-smokers (NS) underwent sputum induction, plasma sampling (to measure IL-6 and
soluble IL-6 receptor [sIL-6R] by immunoassay), monocyte characterization (by
flow cytometry) and monocyte isolation for cell migration and quantitative
polymerase chain reaction studies. Lung tissue was used for immunohistochemistry.
RESULTS: Plasma IL-6 and sIL-6R levels were increased in COPD. Greater
proportions of COPD CD14++CD16+ monocytes expressed CCR5 compared to controls.
Monocyte stimulation with IL-6 and sIL-6R increased CCR5 gene expression. COPD
monocytes demonstrated impaired migration towards sputum supernatant compared to
NS (% migration, 4.4 vs 11.5, respectively; p < 0.05). Pulmonary microvessels
showed reduced monocyte recruitment (% marginated cells) in COPD compared to NS,
(9.3% vs 83.1%, respectively). The proportion of replicating Ki67+ alveolar
macrophages was reduced in COPD compared to NS. All alveolar macrophages from
COPD and S expressed the anti-apoptosis marker BCL2; this protein was not present
in non-smokers or COPD ex-smokers. CONCLUSION: COPD monocytes show decreased
migratory ability despite increased CCR5 expression. Increased COPD lung
macrophage numbers may be due to delayed apoptosis.
PMID- 28494758
TI - Physician job satisfaction related to actual and preferred job size.
AB - BACKGROUND: Job satisfaction is essential for physicians' well-being and patient
care. The work ethic of long days and hard work that has been advocated for
decades is acknowledged as a threat for physicians' job satisfaction, well-being,
and patient safety. Our aim was to determine the actual and preferred job size of
physicians and to investigate how these and the differences between them
influence physicians' job satisfaction. METHOD: Data were retrieved from a
larger, longitudinal study among physicians starting medical training at
Groningen University in 1982/83/92/93 (N = 597). Data from 506 participants (85%)
were available for this study. We used regression analysis to investigate the
influence of job size on physicians' job satisfaction (13 aspects) and ANOVA to
examine differences in job satisfaction between physicians wishing to retain,
reduce or increase job size. RESULTS: The majority of the respondents (57%) had
an actual job size less than 1.0 FTE. More than 80% of all respondents preferred
not to work full-time in the future. Respondents' average actual and preferred
job sizes were .85 FTE and .81 FTE, respectively. On average, respondents who
wished to work less (35% of respondents) preferred a job size reduction of 0.18
FTE and those who wished to work more (12%) preferred an increase in job size of
0.16 FTE. Job size influenced satisfaction with balance work-private hours most
(beta = -.351). Physicians who preferred larger job sizes were - compared to the
other groups of physicians - least satisfied with professional accomplishments.
CONCLUSIONS: A considerable group of physicians reported a gap between actual and
preferred job size. Realizing physicians' preferences as to job size will hardly
affect total workforce, but may greatly benefit individual physicians as well as
their patients and society. Therefore, it seems time for a shift in work ethic.
PMID- 28494760
TI - The Picture Talk Project: Starting a Conversation with Community Leaders on
Research with Remote Aboriginal Communities of Australia.
AB - BACKGROUND: Researchers are required to seek consent from Indigenous communities
prior to conducting research but there is inadequate information about how
Indigenous people understand and become fully engaged with this consent process.
Few studies evaluate the preference or understanding of the consent process for
research with Indigenous populations. Lack of informed consent can impact on
research findings. METHODS: The Picture Talk Project was initiated with senior
Aboriginal leaders of the Fitzroy Valley community situated in the far north of
Western Australia. Aboriginal people were interviewed about their understanding
and experiences of research and consent processes. Transcripts were analysed
using NVivo10 software with an integrated method of inductive and deductive
coding and based in grounded theory. Local Aboriginal interpreters validated
coding. Major themes were defined and supporting quotes sourced. RESULTS:
Interviews with Aboriginal leaders (n = 20) were facilitated by a local
Aboriginal Community Navigator who could interpret if necessary and provide
cultural guidance. Participants were from all four major local language groups of
the Fitzroy Valley; aged 31 years and above; and half were male. Themes emerging
from these discussions included Research-finding knowledge; Being respectful of
Aboriginal people, Working on country, and Being flexible with time; Working
together with good communication; Reciprocity-two-way learning; and Reaching
consent. CONCLUSION: The project revealed how much more there is to be learned
about how research with remote Aboriginal communities should be conducted such
that it is both culturally respectful and, importantly, meaningful for
participants. We identify important elements in community consultation about
research and seeking consent.
PMID- 28494759
TI - Time-resolved dual transcriptomics reveal early induced Nicotiana benthamiana
root genes and conserved infection-promoting Phytophthora palmivora effectors.
AB - BACKGROUND: Plant-pathogenic oomycetes are responsible for economically important
losses in crops worldwide. Phytophthora palmivora, a tropical relative of the
potato late blight pathogen, causes rotting diseases in many tropical crops
including papaya, cocoa, oil palm, black pepper, rubber, coconut, durian, mango,
cassava and citrus. Transcriptomics have helped to identify repertoires of host
translocated microbial effector proteins which counteract defenses and reprogram
the host in support of infection. As such, these studies have helped in
understanding how pathogens cause diseases. Despite the importance of P.
palmivora diseases, genetic resources to allow for disease resistance breeding
and identification of microbial effectors are scarce. RESULTS: We employed the
model plant Nicotiana benthamiana to study the P. palmivora root infections at
the cellular and molecular levels. Time-resolved dual transcriptomics revealed
different pathogen and host transcriptome dynamics. De novo assembly of P.
palmivora transcriptome and semi-automated prediction and annotation of the
secretome enabled robust identification of conserved infection-promoting
effectors. We show that one of them, REX3, suppresses plant secretion processes.
In a survey for early transcriptionally activated plant genes we identified a N.
benthamiana gene specifically induced at infected root tips that encodes a
peptide with danger-associated molecular features. CONCLUSIONS: These results
constitute a major advance in our understanding of P. palmivora diseases and
establish extensive resources for P. palmivora pathogenomics, effector-aided
resistance breeding and the generation of induced resistance to Phytophthora root
infections. Furthermore, our approach to find infection-relevant secreted genes
is transferable to other pathogen-host interactions and not restricted to plants.
PMID- 28494762
TI - The North American opioid epidemic: current challenges and a call for treatment
as prevention.
AB - There is a need for creative, public health-oriented solutions to the
increasingly intractable problems associated with the North American opioid
epidemic. This epidemic is a fundamentally continental problem, as routes of
migration, drug demand, and drug exchange link the USA with Mexico and Canada.
The challenges faced throughout North America include entrenched prescribing
practices of opioid medications, high costs and low availability of medication
assisted treatment (MAT), and policy approaches that present substantial barriers
to care.We advocate for the scale up of a low-threshold treatment model for MAT
that incorporates the best practices in addiction treatment. Such a model would
remove barriers to care through widespread treatment availability and
affordability and also a policy of decriminalization. Given that MAT reduces the
frequency of drug injecting among opioid injectors, this treatment model should
also be guided by an understanding of the socially communicable nature of
injection drug use, such that increasing MAT availability may also prevent the
spread of injecting practices to individuals at risk of transitions from non
injection to injection drug use. To that end, the "Treatment as Prevention" model
employed to respond to the individual- and population-level risks for HIV/AIDS
prevention could be adapted to efforts to halt the North American opioid
epidemic.
PMID- 28494761
TI - Production of fuels and chemicals from xylose by engineered Saccharomyces
cerevisiae: a review and perspective.
AB - Efficient xylose utilization is one of the most important pre-requisites for
developing an economic microbial conversion process of terrestrial
lignocellulosic biomass into biofuels and biochemicals. A robust ethanol
producing yeast Saccharomyces cerevisiae has been engineered with heterologous
xylose assimilation pathways. A two-step oxidoreductase pathway consisting of
NAD(P)H-linked xylose reductase and NAD+-linked xylitol dehydrogenase, and one
step isomerase pathway using xylose isomerase have been employed to enable xylose
assimilation in engineered S. cerevisiae. However, the resulting engineered yeast
exhibited inefficient and slow xylose fermentation. In order to improve the yield
and productivity of xylose fermentation, expression levels of xylose assimilation
pathway enzymes and their kinetic properties have been optimized, and additional
optimizations of endogenous or heterologous metabolisms have been achieved. These
efforts have led to the development of engineered yeast strains ready for the
commercialization of cellulosic bioethanol. Interestingly, xylose metabolism by
engineered yeast was preferably respiratory rather than fermentative as in
glucose metabolism, suggesting that xylose can serve as a desirable carbon source
capable of bypassing metabolic barriers exerted by glucose repression.
Accordingly, engineered yeasts showed superior production of valuable metabolites
derived from cytosolic acetyl-CoA and pyruvate, such as 1-hexadecanol and lactic
acid, when the xylose assimilation pathway and target synthetic pathways were
optimized in an adequate manner. While xylose has been regarded as a sugar to be
utilized because it is present in cellulosic hydrolysates, potential benefits of
using xylose instead of glucose for yeast-based biotechnological processes need
to be realized.
PMID- 28494764
TI - Possible benefits of tomato juice consumption: a pilot study on irradiated human
lymphocytes from healthy donors.
AB - BACKGROUND: Reactive oxygen species (ROS) mediate much of the DNA damage caused
by ionizing radiation. Among carotenoids, lycopene and beta-carotene, present in
tomato juice, are known to be strong radical scavengers. The aim of the study was
to investigate the effect of tomato juice intake on the levels of DNA damage and
oxidative stress in human whole blood induced by in vitro exposure to X-rays.
METHODS: Ten healthy adults were asked to drink 190 g of tomato juice, containing
17 mg lycopene and 0.25 mg beta-carotene, per day for 3 weeks and then refrain
from drinking it for 3 weeks. Peripheral whole blood samples were collected
before and after the intake period of tomato juice and after the washout period.
The blood samples were exposed in vitro to X-ray doses of 0, 0.1, 0.5, and 2 Gy.
Cytogenetic damage was measured using the cytokinesis-block micronucleus (CBMN)
assay and the dicentrics (DIC) assay. The level of oxidative stress was
determined using serum 8-oxo-7, 8-dihydro-2-deoxyguanosine (8-oxo-dG) and plasma
reactive oxygen metabolite-derived compounds (d-ROMs). The concentration of
carotenoids in plasma was measured at the three time points. RESULTS: The levels
of 8-oxo-dG tended to decrease during the intake period and increase during the
washout period. A non-significant inverse correlation was noted between the
plasma concentration of lycopene plus beta-carotene and the level of 8-oxo-dG (P
= 0.064). The radiation-induced MN and DIC frequencies increased in a dose
dependent manner, and when compared at the same dose, the MN and DIC frequencies
decreased during the intake period compared with those at baseline and then
increased during the washout period. The results suggest that continuous tomato
juice consumption non-significantly decreases extracellular 8-oxo-dG, d-ROMs, and
MN. Tomato juice intake had minimal or no effect on radiation-induced 8-oxo-dG
and d-ROMs. For most radiation doses, continuously tomato juice intake lowered
the levels of MN and DIC. CONCLUSION: Tomato juice consumption may suppress human
lymphocyte DNA damage caused by radiation, but further examination is required.
TRIAL REGISTRATION: 2014-001 and 2014-R06.
PMID- 28494763
TI - Artemisinin resistance without pfkelch13 mutations in Plasmodium falciparum
isolates from Cambodia.
AB - BACKGROUND: Artemisinin resistance is associated with delayed parasite clearance
half-life in vivo and correlates with ring-stage survival under
dihydroartemisinin in vitro. Both phenotypes are associated with mutations in the
PF3D7_1343700 pfkelch13 gene. Recent spread of artemisinin resistance and
emerging piperaquine resistance in Southeast Asia show that artemisinin
combination therapy, such as dihydroartemisinin-piperaquine, are losing clinical
effectiveness, prompting investigation of drug resistance mechanisms and
development of strategies to surmount emerging anti-malarial resistance. METHODS:
Sixty-eight parasites isolates with in vivo clearance data were obtained from two
Tracking Resistance to Artemisinin Collaboration study sites in Cambodia, culture
adapted, and genotyped for pfkelch13 and other mutations including pfmdr1 copy
number; and the RSA0-3h survival rates and response to antimalarial drugs in
vitro were measured for 36 of these isolates. RESULTS: Among these 36 parasites
one isolate demonstrated increased ring-stage survival for a PfKelch13 mutation
(D584V, RSA0-3h = 8%), previously associated with slow clearance but not yet
tested in vitro. Several parasites exhibited increased ring-stage survival, yet
lack pfkelch13 mutations, and one isolate showed evidence for piperaquine
resistance. CONCLUSIONS: This study of 68 culture-adapted Plasmodium falciparum
clinical isolates from Cambodia with known clearance values, associated the D584V
PfKelch13 mutation with increased ring-stage survival and identified parasites
that lack pfkelch13 mutations yet exhibit increased ring-stage survival. These
data suggest mutations other than those found in pfkelch13 may be involved in
conferring artemisinin resistance in P. falciparum. Piperaquine resistance was
also detected among the same Cambodian samples, consistent with reports of
emerging piperaquine resistance in the field. These culture-adapted parasites
permit further investigation of mechanisms of both artemisinin and piperaquine
resistance and development of strategies to prevent or overcome anti-malarial
resistance.
PMID- 28494765
TI - Duration of the common cold and similar continuous outcomes should be analyzed on
the relative scale: a case study of two zinc lozenge trials.
AB - BACKGROUND: The relative scale has been used for decades in analysing binary data
in epidemiology. In contrast, there has been a long tradition of carrying out
meta-analyses of continuous outcomes on the absolute, original measurement,
scale. The biological rationale for using the relative scale in the analysis of
binary outcomes is that it adjusts for baseline variations; however, similar
baseline variations can occur in continuous outcomes and relative effect scale
may therefore be often useful also for continuous outcomes. The aim of this study
was to determine whether the relative scale is more consistent with empirical
data on treating the common cold than the absolute scale. METHODS: Individual
patient data was available for 2 randomized trials on zinc lozenges for the
treatment of the common cold. Mossad (Ann Intern Med 125:81-8, 1996) found 4.0
days and 43% reduction, and Petrus (Curr Ther Res 59:595-607, 1998) found 1.77
days and 25% reduction, in the duration of colds. In both trials, variance in the
placebo group was significantly greater than in the zinc lozenge group. The
effect estimates were applied to the common cold distributions of the placebo
groups, and the resulting distributions were compared with the actual zinc
lozenge group distributions. RESULTS: When the absolute effect estimates, 4.0 and
1.77 days, were applied to the placebo group common cold distributions, negative
and zero (i.e., impossible) cold durations were predicted, and the high level
variance remained. In contrast, when the relative effect estimates, 43 and 25%,
were applied, impossible common cold durations were not predicted in the placebo
groups, and the cold distributions became similar to those of the zinc lozenge
groups. CONCLUSIONS: For some continuous outcomes, such as the duration of
illness and the duration of hospital stay, the relative scale leads to a more
informative statistical analysis and more effective communication of the study
findings. The transformation of continuous data to the relative scale is simple
with a spreadsheet program, after which the relative scale data can be analysed
using standard meta-analysis software. The option for the analysis of relative
effects of continuous outcomes directly from the original data should be
implemented in standard meta-analysis programs.
PMID- 28494767
TI - Intestinal differentiated mucinous adenocarcinoma of the endometrium with
sporadic MSI high status: a case report.
AB - BACKGROUND: Intestinal differentiation of primary mucinous adenocarcinoma of the
uterine corpus is exceedingly rare in comparison to the approximately 25% rate in
endocervical and ovarian mucinous carcinoma. Additionally, little is known about
the related genetic and epigenetic alterations, even though large-scale molecular
characterisation of the different types of endometrial cancer took place in the
TCGA project along the entities defined by the recent WHO classification. CASE
PRESENTATION: We present a 62-year-old patient harbouring a primary mucinous
carcinoma of the uterine corpus with a morphological resemblance to mucinous
colorectal adenocarcinoma. The intestinal differentiation was substantiated by
CDX2 and CK20 positivity in the absence of PAX8, p16, WT1, p53, ER, PgR, AFP,
SALL4 and Glypican3. A high MSI status with MLH1 hypermethylation was revealed by
molecular testing. CONCLUSION: Intestinal differentiation of mucinous
adenocarcinoma of the endometrium is a unique observation. Besides morphology, it
obviously can share molecular features of sporadic MSI colorectal cancers. It can
be speculated that either CDX2 positive morula formation or intestinal metaplasia
of the endometrium as rare conditions might be the origin of carcinogenesis for
this type II endometrial cancer. Both conditions were not detectable in this
case. Of note, categorising endometrial cancers in genetic subgroups like MSI
high cancers alone might lead to the integration of likewise morphologically
different tumours like the case presented here with intestinal differentiation.
Hence, careful genotype-phenotype correlations are warranted for studies of
mucinous adenocarcinoma of the endometrium.
PMID- 28494769
TI - Retraction Note: Anti-cancer effects of grailsine-al-glycoside isolated from
Rhizoma Sparganii.
PMID- 28494766
TI - FilmArrayTM GI panel performance for the diagnosis of acute gastroenteritis or
hemorragic diarrhea.
AB - BACKGROUND: Acute gastroenteritis is a common cause of morbidity and mortality in
humans worldwide. The rapid and specific identification of infectious agents is
crucial for correct patient management. However, diagnosis of acute
gastroenteritis is usually performed with diagnostic panels that include only a
few pathogens. In the present bicentric study, the diagnostic value of
FilmArrayTM GI panels was assessed in unformed stool samples of patients with
acute gastroenteritis and in a series of samples collected from pediatric
patients with heamorragic diarrhea. The clinical performance of the FilmArrayTM
gastrointestinal (GI) panel was assessed in 168 stool samples collected from
patients with either acute gastroenteritis or hemorragic diarrhea. Samples
showing discordant results between FilmArray and routine methods were further
analyzed with an additional assay. RESULTS: Overall, the FilmArrayTM GI panel
detected at least one potential pathogen in 92/168 (54.8%) specimens. In 66/92
(71.8%) samples, only one pathogen was detected, while in 26/92 (28.2%) multiple
pathogens were detected. The most frequent pathogens were rotavirus 13.9%
(22/168), Campylobacter 10.7% (18/168), Clostridium difficile 9.5% (16/168), and
norovirus 8.9% (15/168). Clostridium difficile was identified only in patients
with acute gastroenteritis (p < 0.01), while STEC was detected exclusively in
patients with hemorragic diarrhea (p < 0.01). In addition, Campylobacter spp.,
Salmonella spp., EPEC and E. coli producing Shiga-like toxin were more frequently
detected in patients with hemorragic diarrhea (p < 0.05). The overall percent
agreement calculated in samples was 73.8% and 65.5%, while 34.5% were discordant.
After additional confirmatory analyses, the proportion of discordant samples
decreased to 7.7%. Rotavirus and astrovirus were the most frequently unconfirmed
pathogens. CONCLUSION: In conclusion, the FilmArrayTM GI panel has proved to be a
valuable new diagnostic tool for improving the diagnostic efficiency of GI
pathogens.
PMID- 28494770
TI - Exploring linkages between research, policy and practice in the Netherlands:
perspectives on sexual and reproductive health and rights knowledge flows.
AB - BACKGROUND: The attention to and demand for stronger linkages between research,
policy and practice are increasing, especially in fields concerned with sensitive
and challenging issues such as sexual and reproductive health and rights (SRHR).
The study described in this article was conducted in the Netherlands among actors
working in international development, especially the domain of SRHR. It explores
the perceived flow of knowledge between research, policy and practice, the
perceived impeding factors, and suggested strategies for improvement. METHODS: A
narrative literature review was performed and 28 key informants were interviewed
between May and August 2015. Most interviewees were either active or passive
members of Share-Net Netherlands, an SRHR knowledge platform. All interviews,
which lasted 70 minutes on average, were recorded, transcribed verbatim and coded
in MAXQDA. RESULTS: Linkages between research, policy and practice are many and
diffuse. The demands for and supplies of knowledge within and across the fields
vary and do not always match, which is shown by participants' research purposes
and approaches. Participants identified various barriers to strengthening
knowledge flows, including a lack of familiarity with practices in other fields,
power relations and the undervaluation of tacit knowledge. They suggested a more
visible and concrete demand for and supply of knowledge, the development of a
joint knowledge agenda, more opportunities for the interdisciplinary creation of
knowledge, and the development of a system for learning and sharing knowledge.
CONCLUSION: This study shows the willingness to undertake, and the perceived
advantages of, interdisciplinary dialogues and joint creation of knowledge to
advance SRHR research, policies and practices. Whereas barriers to the flow of
knowledge may maintain present understandings of knowledge and of whose knowledge
is valid, enabling factors, such as interactions between research, policy and
practice in knowledge-sharing activities, may challenge such perceptions and
create an enabling environment for generating innovative knowledge and increasing
knowledge use. Knowledge platforms are recommended to place more emphasis on
sharing and documenting tacit knowledge through interdisciplinary dialogues, to
address power relations and to set criteria for interdisciplinary funding.
PMID- 28494771
TI - Probable DRESS syndrome induced by IL-1 inhibitors.
AB - Interleukin (IL)-1 inhibitors have been increasingly used for treating
autoinflammatory diseases during the last 10 years, but the spectrum of their
possible side effects is not yet fully known. Here, we bring physicians'
attention to a new severe complication of IL-1 inhibitors, manifesting as a
probable drug reaction with eosinophilia and systemic symptoms (DRESS) in two
patients.
PMID- 28494768
TI - Inhibition of CD40-TRAF6 interactions by the small molecule inhibitor 6877002
reduces neuroinflammation.
AB - BACKGROUND: The influx of leukocytes into the central nervous system (CNS) is a
key hallmark of the chronic neuro-inflammatory disease multiple sclerosis (MS).
Strategies that aim to inhibit leukocyte migration across the blood-brain barrier
(BBB) are therefore regarded as promising therapeutic approaches to combat MS. As
the CD40L-CD40 dyad signals via TNF receptor-associated factor 6 (TRAF6) in
myeloid cells to induce inflammation and leukocyte trafficking, we explored the
hypothesis that specific inhibition of CD40-TRAF6 interactions can ameliorate
neuro-inflammation. METHODS: Human monocytes were treated with a small molecule
inhibitor (SMI) of CD40-TRAF6 interactions (6877002), and migration capacity
across human brain endothelial cells was measured. To test the therapeutic
potential of the CD40-TRAF6-blocking SMI under neuro-inflammatory conditions in
vivo, Lewis rats and C57BL/6J mice were subjected to acute experimental
autoimmune encephalomyelitis (EAE) and treated with SMI 6877002 for 6 days (rats)
or 3 weeks (mice). RESULTS: We here show that a SMI of CD40-TRAF6 interactions
(6877002) strongly and dose-dependently reduces trans-endothelial migration of
human monocytes. Moreover, upon SMI treatment, monocytes displayed a decreased
production of ROS, tumor necrosis factor (TNF), and interleukin (IL)-6, whereas
the production of the anti-inflammatory cytokine IL-10 was increased. Disease
severity of EAE was reduced upon SMI treatment in rats, but not in mice. However,
a significant reduction in monocyte-derived macrophages, but not in T cells, that
had infiltrated the CNS was eminent in both models. CONCLUSIONS: Together, our
results indicate that SMI-mediated inhibition of the CD40-TRAF6 pathway skews
human monocytes towards anti-inflammatory cells with reduced trans-endothelial
migration capacity, and is able to reduce CNS-infiltrated monocyte-derived
macrophages during neuro-inflammation, but minimally ameliorates EAE disease
severity. We therefore conclude that SMI-mediated inhibition of the CD40-TRAF6
pathway may represent a beneficial treatment strategy to reduce monocyte
recruitment and macrophage activation in the CNS and has the potential to be used
as a co-treatment to combat MS.
PMID- 28494772
TI - Anti-claudin 18.2 antibody as new targeted therapy for advanced gastric cancer.
AB - Targeted therapy and immunotherapy have revolutionized treatment of various
cancers in the past decade. Despite targeted therapy with trastuzumab in Her2
positive gastric cancer patients, survival has been dismal, mostly due to disease
progression and toxicity related to the treatments. One area of active
development is looking for ideal monoclonal antibodies (IMAB) specific to the
proteins only on the tumor and hence avoiding unnecessary side effects. Claudin
proteins with isoform 2 are one such protein, specific for several cancers,
particularly gastric cancer and its metastases, leading to the development of
anti-claudin 18.2 specific antibody, claudiximab. This review will highlight the
latest development of claudiximab as first in class IMAB for the treatment of
gastric cancer.
PMID- 28494773
TI - Domains of quality of life freely expressed by cancer patients and their
caregivers: contribution of the SEIQoL.
AB - BACKGROUND: The purposes of this study, performed on a large sample of cancer
patient-caregiver dyads, were: i) to simultaneously investigate, using an
individualized quality of life (QoL) measure (Schedule for the Evaluation of
Individual QoL, SEIQoL), the QoL domains freely expressed by cancer patients and
their caregivers, and ii) to explore overlapping between the SEIQoL assessment
and QoL assessment using traditional instruments. METHODS: The study employed a
cross-sectional design including cancer patients who were going to receive
chemotherapy treatment and their caregivers. Quality of life was assessed using
condition-specific questionnaires (EORTC QLQ-C30 and CarGOQoL), generic health
related questionnaire (SF-36), and open individualized measure (SEIQoL). RESULTS:
The final sample included 205 patient-caregiver dyads. From the SEIQoL, Family,
Health, and Leisures were the most freely expressed QoL domains by patients and
caregivers, but reported with different weights. Love life and financial issues
were less spontaneously mentioned. The SEIQoL index was moderately correlated to
the condition-specific QoL questionnaires (R lower than |0.40|) and to SF-36
(correlation coefficients: R ranging from 0.17 to 0.31). CONCLUSION:
Individualized QoL measures allow individuals to spontaneously express important,
non-predefined domains. This study highlights the need to explore QoL using a
combination of individualized questionnaires and standardized questionnaires,
capturing complementary facets that patients consider important in their life.
PMID- 28494774
TI - Expanding conceptualizations of harm reduction: results from a qualitative
community-based participatory research study with people who inject drugs.
AB - BACKGROUND: The perspectives of people who use drugs are critical in
understanding why people choose to reduce harm in relation to drug use, what
practices are considered or preferred in conceptualizations of harm reduction,
and which environmental factors interfere with or support the use of harm
reduction strategies. This study explores how people who inject drugs (PWID)
think about harm reduction and considers the critical imperative of equity in
health and social services delivery for this community. METHODS: This community
based participatory research study was conducted in a Canadian urban centre.
Using a peer-based recruitment and interviewing strategy, semi-structured
qualitative interviews were conducted by and with PWID. The Vidaview Life Story
Board, an innovative tool where interviewers and participant co-construct a
visual "life-scape" using a board, markers, and customized picture magnets, was
used to facilitate the interviews. The topics explored included injection drug
use and harm reduction histories, facilitators and barriers to using harm
reduction strategies, and suggestions for improving services and supports.
RESULTS: Twenty-three interviews with PWID (14 men and 9 women) were analysed,
with a median age of 50. Results highlighted an expanded conceptualization of
harm reduction from the perspectives of PWID, including motivations for adopting
harm reduction strategies and a description of harm reduction practices that went
beyond conventional health-focused concerns. The most common personal practices
that PWID used included working toward moderation, employing various cognitive
strategies, and engaging in community activities. The importance of social or
peer support and improving self-efficacy was also evident. Further, there was a
call for less rigid eligibility criteria and procedures in health and social
services, and the need to more adequately address the stigmatization of drug
users. CONCLUSIONS: These findings demonstrated that PWID incorporate many
personal harm reduction practices in their daily lives to improve their well
being, and these practices highlight the importance of agency, self-care, and
community building. Health and social services are needed to better support these
practices because the many socio-structural barriers this community faces often
interfere with harm reduction efforts. Finally, "one size does not fit all" when
it comes to harm reduction, and more personalized or de-medicalized
conceptualizations are recommended.
PMID- 28494775
TI - Gender blind? An analysis of global public-private partnerships for health.
AB - BACKGROUND: The Global Public Private Partnerships for Health (GPPPH) constitute
an increasingly central part of the global health architecture and carry both
financial and normative power. Gender is an important determinant of health
status, influencing differences in exposure to health determinants, health
behaviours, and the response of the health system. We identified 18 GPPPH -
defined as global institutions with a formal governance mechanism which includes
both public and private for-profit sector actors - and conducted a gender
analysis of each. RESULTS: Gender was poorly mainstreamed through the
institutional functioning of the partnerships. Half of these partnerships had no
mention of gender in their overall institutional strategy and only three
partnerships had a specific gender strategy. Fifteen governing bodies had more
men than women - up to a ratio of 5:1. Very few partnerships reported sex
disaggregated data in their annual reports or coverage/impact results. The
majority of partnerships focused their work on maternal and child health and
infectious and communicable diseases - none addressed non-communicable diseases
(NCDs) directly, despite the strong role that gender plays in determining risk
for the major NCD burdens. CONCLUSIONS: We propose two areas of action in
response to these findings. First, GPPPH need to become serious in how they "do"
gender; it needs to be mainstreamed through the regular activities, deliverables
and systems of accountability. Second, the entire global health community needs
to pay greater attention to tackling the major burden of NCDs, including
addressing the gendered nature of risk. Given the inherent conflicts of interest
in tackling the determinants of many NCDs, it is debatable whether the emergent
GPPPH model will be an appropriate one for addressing NCDs.
PMID- 28494776
TI - Aggregated N-of-1 trials for unlicensed medicines for small populations: an
assessment of a trial with ephedrine for myasthenia gravis.
AB - BACKGROUND: Inexpensive medicines with a long history of use may currently be
prescribed off-label for rare indications. Reimbursement is at the discretion of
health insurance companies, and may be unpredictable. The example addressed was
ephedrine as add-on treatment for myasthenia gravis. Stakeholders from academia,
a patient organization, the Dutch National Health Care Institute (NHCI) and Dutch
Medicines Evaluation Board (MEB) advised on the trial design. The NHCI and MEB
agreed to provide scientific advice on the suitability of the evidence generated
by the trial, for regulatory decisions. This paper describes the feasibility of
the trial and the utility of its aggregated results. RESULTS: The trialists
experienced the trial as feasible. Retrospective interviews showed that the trial
as performed was acceptable to patients. The treatment effect in the primary
outcome measure, muscle strength, was statistically significant when inferred to
the population level, though the effect size was modest. Secondary outcomes were
statistically significant in a preplanned, fixed effects analysis within the four
patients. The NHCI advised that it could potentially make reimbursement decisions
based on the Fitting Evidence framework, should the trialists decide to apply for
reimbursement. The MEB advised that for a licensing decision, the N-of-1 design
is a last-resort option for demonstrating treatment benefit in a rare disease. N
of-1 trials alone do not provide enough evidence on potential risk. The MEB found
the current trial inconclusive. It suggested doing a 2-armed trial of longer
duration, possibly with a different outcome measure (postponement of
corticosteroid use). It suggested engaging a consultancy or commercial sponsor,
should the trialists decide to seek market authorization of the drug.
CONCLUSIONS: In theory, evidence from aggregated N-of-1 trials is suitable for
use in licensing and reimbursement decisions. The current example illustrates
differences in interpretation of N-of-1 results by health authorities. In the era
of personalized medicine, consensus is required on the interpretation of data
from study designs geared to small groups. Demonstrating effectiveness of
inexpensive medicines in small populations may require involvement of non
commercial parties, to preserve affordability.
PMID- 28494777
TI - Platelet desialylation is a novel mechanism and a therapeutic target in
thrombocytopenia during sepsis: an open-label, multicenter, randomized controlled
trial.
AB - BACKGROUND: Studies in murine models suggested that platelet desialylation was an
important mechanism of thrombocytopenia during sepsis. METHODS: First, we
performed a prospective, multicenter, observational study that enrolled septic
patients with or without thrombocytopenia to determine the association between
platelet desialylation and thrombocytopenia in patients with sepsis, severe
sepsis, and septic shock. Gender- and age-matched healthy adults were selected as
normal controls in analysis of the platelet desialylation levels (study I). Next,
we conducted an open-label randomized controlled trial (RCT) in which the
patients who had severe sepsis with thrombocytopenia (platelet counts <=50 *
109/L) were randomly assigned to receive antimicrobial therapy alone (control
group) or antimicrobial therapy plus oseltamivir (oseltamivir group) in a 1:1
ratio (study II). The primary outcomes were platelet desialylation level at study
entry, overall platelet response rate within 14 days post-randomization, and all
cause mortality within 28 days post-randomization. Secondary outcomes included
platelet recovery time, the occurrence of bleeding events, and the amount of
platelets transfused within 14 days post-randomization. RESULTS: The platelet
desialylation levels increased significantly in the 127 septic patients with
thrombocytopenia compared to the 134 patients without thrombocytopenia. A
platelet response was achieved in 45 of the 54 patients in the oseltamivir group
(83.3%) compared with 34 of the 52 patients in the control group (65.4%; P =
0.045). The median platelet recovery time was 5 days (interquartile range 4-6) in
the oseltamivir group compared with 7 days (interquartile range 5-10) in the
control group (P = 0.003). The amount of platelets transfused decreased
significantly in the oseltamivir group compared to the control group (P = 0.044).
There was no difference in the overall 28-day mortality regardless of whether
oseltamivir was used. The Sequential Organ Failure Assessment score and platelet
recovery time were independent indicators of oseltamivir therapy. The main reason
for all of the mortalities was multiple-organ failure. CONCLUSIONS:
Thrombocytopenia was associated with increased platelet desialylation in septic
patients. The addition of oseltamivir could significantly increase the platelet
response rate, shorten platelet recovery time, and reduce platelet transfusion.
TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IPR-16008542 .
PMID- 28494778
TI - Lysophosphatidylcholine acyltransferase 1 upregulation and concomitant
phospholipid alterations in clear cell renal cell carcinoma.
AB - BACKGROUND: The involvement of lipid metabolism in tumourigenesis and the
progression of clear cell renal cell carcinoma (ccRCC) have been reported.
However, the role of phospholipid profile alterations in ccRCC has not yet been
systematically explored. In the present study, we compared the phospholipid
compositions between ccRCC and paired normal renal tissues. METHODS: The
phospholipid compositions of paired ccRCC and normal renal tissues were evaluated
using liquid chromatography tandem mass spectrometry (LC/MS/MS). To evaluate the
mRNA and protein levels of lysophosphatidylcholine acyltransferase (LPCAT), which
converts lysophosphatidylcholine (LPC) to phosphatidylcholine (PC), qRT-PCR,
western blotting and immunohistochemistry were performed. The correlations of
LPCAT1 expression with clinicopathological features and prognosis were assessed.
In addition, siRNAs were used to knockdown LPCAT1 expression in ccRCC cell lines,
and its effect on cell proliferation, cell cycle, migration and invasion were
investigated. RESULTS: The phospholipid compositions of ccRCC and normal renal
tissues were significantly different. Multiple LPC species were decreased and
corresponding PC species were increased in cancer tissues. The mRNA and protein
levels of LPCAT1 were up-regulated in ccRCC tissues compared with normal renal
tissues, and LPCAT1 expression was significantly correlated with unfavourable
pathological features (higher tumour grade, higher TNM stage and larger tumour
size) and overall survival. In cell line experiments, LPCAT1 knockdown depleted
PCs, inhibited cell proliferation, migration and invasion and induced cell cycle
arrest at the G0/G1 phase. CONCLUSION: Selective changes in PC and LPC
composition were observed in ccRCC tissues. The overexpression of LPCAT1 promotes
the development and progression of ccRCC, likely through the conversion of LPC to
PC.
PMID- 28494779
TI - Blood homocysteine concentration and mood disorders with mixed features among
patients with alcohol use disorder.
AB - BACKGROUND: Blood homocysteine concentration (BHC) is higher in patients with
alcohol use disorder (AUD). Previous studies have found a relationship between
depressive symptoms severity and BHC in AUD patients and recently some authors
have found high BHC among patients with bipolar disorder, both during manic and
depressive episodes and in euthymic state. However, BHC in patients with mixed
mood episode has not yet been investigated. The aim of this study was to evaluate
the BHC of patients with AUD and mixed mood episode. METHODS: A sample of AUD
outpatients was assessed by Mini-International Neuropsychiatric Interview (MINI
Plus): those with a DSM-IV-TR mood disorder with mixed features were included in
the MIXED group (n = 45), whereas those without mood episode were gathered in the
NO MOOD group (n = 23). Two subgroups, MIXMANIA and MIXDEPRESSION, were formed
according to the prevalence of manic or depressive symptoms, assessed by Young
Mania Rating Scale (YMRS), and Hamilton Rating Scale for Depression (HDRS). The
Alcohol Use Disorder Identification Test (AUDIT) was used to appraise the AUD.
BHC was determined by High-Performance Liquid Chromatography. RESULTS: The MIXED
group showed greater severity of both depressive (26.35 +/- 9.96 vs. 4.77 +/-
0.92; p < 0.001) and manic (22.35 +/- 3.30 vs. 6.14 +/- 1.12; p < 0.001)
symptoms, and higher BHC (28.80 +/- 11.47 vs. 10.83 +/- 2.81; p < 0.001), than
the NO MOOD group. BHC was strongly correlated to the HDRS, YMRS and AUDIT
scores, just as HDRS was to YMRS, and AUDIT was to both HDRS and YMRS, in the
MIXED group only (p < 0.001). The MIXDEPRESSION subgroup showed higher BHC than
the MIXMANIA subgroup (Mdn = 42.96, IQR = 10.44 vs. Mdn = 19.77, IQR = 5.93; p <
0.001). A linear regression model conducted on the MIXED group found a
significant predictive value for BHC of both HDRS (beta = 0.560, t = 2.43, p =
0.026) and AUDIT (beta = 0.348, t = 2.17, p = 0.044). CONCLUSIONS: Depressive
symptoms seem to be mainly implicated in the BHC elevation among patients with
both mixed features mood disorder and AUD.
PMID- 28494780
TI - Metastatic non-muscle invasive bladder cancer with meningeal carcinomatosis: case
report of an unexpected response.
AB - BACKGROUND: Non-muscle invasive bladder cancer (NMIBC) is usually treated with
local therapy including transurethral resection of the bladder tumor and
intravesical therapy depending on the stage of the tumor. NMIBC is a rarely a
metastatic diseases with lymph node invasion in less of 10%. In the other hand
meningeal carcinomatosis is a rare location for metastases with extremely poor
outcomes. We described a case report of a patient presenting a metastatic disease
to bones and meninges, several years after the treatment of NMIBC, which had been
in complete response (CR) for 4 years after chemotherapy treatment. CASE
PRESENTATION: A 63-years old men was treated by TURBT in 2008 for a high grade
NMIBC, pT1b. Three years later he presented an acute binocular diplopy with right
trochlear nerve paralysis, and labial hypoesthesia. Brain scan and MRI were
performed finding a clivus infiltration and a pachymeningitis. A vertebral biopsy
was performed finding an invasive carcinoma, CK7+/CK20+, TTF1-, PSA-,
Thyroglobulin- and GATA3+. The metastatic event was in relation to the high grade
NMIBC treated 3 years previously. Palliative chemotherapy was started with
cisplatin gemcitabine. After 6 cycles and to date, 4 years later, the patient is
therefore considered in complete response. CONCLUSION: Metastasis in non-muscle
invasive urothelial carcinoma is rare. Meningeal carcinomatosis outcome is poor,
usually appearing in widely metastatic and progressive cancers but also because
most systemic agents fail to pass the blood-brain barrier and penetrate into the
cerebrospinal fluid. We described an unexpected response with complete response
after chemotherapy for meningeal carcinomatosis of non muscle invasive urothelial
carcinoma.
PMID- 28494781
TI - Preparation and characterization of small-diameter decellularized scaffolds for
vascular tissue engineering in an animal model.
AB - BACKGROUND: The development of a suitable extracellular matrix (ECM) scaffold is
the first step in vascular tissue engineering (VTE). Synthetic vascular grafts
are available as an alternative to autologous vessels in large-diameter arteries
(>8 mm) and medium-diameter arteries (6-8 mm). In small-diameter vessels (<6 mm),
synthetic vascular grafts are of limited use due to poor patency rates. Compared
with a vascular prosthesis, natural tissue ECM has valuable advantages. Despite
considerable progress in recent years, identifying an optimal protocol to create
a scaffold for use in small-diameter (<6 mm) fully natural tissue-engineered
vascular grafts (TEVG), remains elusive. Although reports on different
decellularization techniques have been numerous, combination of and comparison
between these methods are scarce; therefore, we have compared five different
decellularization protocols for making small-diameter (<6 mm) ECM scaffolds and
evaluated their characteristics relative to those of fresh vascular controls.
RESULTS: The protocols differed in the choice of enzymatic digestion solvent, the
use of non-ionic detergent, the durations of the individual steps, and UV
crosslinking. Due to their small diameter and ready availability, rabbit arteria
carotis were used as the source of the ECM scaffolds. The scaffolds were
subcutaneously implanted in rats and the results were evaluated using various
microscopy and immunostaining techniques. CONCLUSIONS: Our findings showed that a
2 h digestion time with 1* EDTA, replacing non-ionic detergent with double
distilled water for rinsing and the application of UV crosslinking gave rise to
an ECM scaffold with the highest biocompatibility, lowest cytotoxicity and best
mechanical properties for use in vivo or in situ pre-clinical research in VTE in
comparison.
PMID- 28494782
TI - Health workforce and governance: the crisis in Nigeria.
AB - BACKGROUND: In Nigeria, several challenges have been reported within the health
sector, especially in training, funding, employment, and deployment of the health
workforce. We aimed to review recent health workforce crises in the Nigerian
health sector to identify key underlying causes and provide recommendations
toward preventing and/or managing potential future crises in Nigeria. METHODS: We
conducted a scoping literature search of PubMed to identify studies on health
workforce and health governance in Nigeria. A critical analysis, with extended
commentary, on recent health workforce crises (2010-2016) and the health system
in Nigeria was conducted. RESULTS: The Nigerian health system is relatively weak,
and there is yet a coordinated response across the country. A number of health
workforce crises have been reported in recent times due to several months'
salaries owed, poor welfare, lack of appropriate health facilities and emerging
factions among health workers. Poor administration and response across different
levels of government have played contributory roles to further internal crises
among health workers, with different factions engaged in protracted supremacy
challenge. These crises have consequently prevented optimal healthcare delivery
to the Nigerian population. CONCLUSIONS: An encompassing stakeholders' forum in
the Nigerian health sector remain essential. The national health system needs a
solid administrative policy foundation that allows coordination of priorities and
partnerships in the health workforce and among various stakeholders. It is hoped
that this paper may prompt relevant reforms in health workforce and governance in
Nigeria toward better health service delivery in the country.
PMID- 28494783
TI - Genome-wide association study confirm major QTL for backfat fatty acid
composition on SSC14 in Duroc pigs.
AB - BACKGROUND: Fatty acid composition contributes importantly to meat quality and is
essential to the nutritional value of the meat. Identification of genetic factors
underlying levels of fatty acids can be used to breed for pigs with healthier
meat. The aim of this study was to conduct genome-wide association studies (GWAS)
to identify QTL regions affecting fatty acid composition in backfat from the pig
breeds Duroc and Landrace. RESULTS: Using data from the Axiom porcine 660 K
array, we performed GWAS on 454 Duroc and 659 Landrace boars for fatty acid
phenotypes measured by near-infrared spectroscopy (NIRS) technology (C16:0,
C16:1n-7, C18:0, C18:1n-9, C18:2n-6, C18:3n-3, total saturated fatty acids,
monounsaturated fatty acids and polyunsaturated fatty acids). Two QTL regions on
SSC4 and SSC14 were identified in Duroc for the de novo synthesized fatty acids
traits, whereas one QTL on SSC8 was detected in Landrace for C16:1n-7. The QTL
region on SSC14 has been reported in previous studies and a putative causative
mutation has been suggested in the promoter region of the SCD gene. Whole genome
re-sequencing data was used for genotype imputation and to fine map the SSC14 QTL
region in Norwegian Duroc. This effort confirms the location of the QTL on this
chromosome as well as suggesting other putative candidate genes in the region.
The most significant single nucleotide polymorphisms (SNPs) located on SSC14
explain between 55 and 76% of the genetic variance and between 27 and 54% of the
phenotypic variance for the de novo synthesized fatty acid traits in Norwegian
Duroc. For the QTL region on SSC8 in Landrace, the most significant SNP explained
19% of the genetic variance and 5% of the phenotypic variance for C16:1n-7.
CONCLUSIONS: This study confirms a major QTL affecting fatty acid composition on
SSC14 in Duroc, which can be used in genetic selection to increase the level of
fatty acid desaturation. The SSC14 QTL was not segregating in the Landrace
population, but another QTL on SSC8 affecting C16:1n-7 was identified and might
be used to increase the level of desaturation in meat products from this breed.
PMID- 28494784
TI - Influence of neoadjuvant chemotherapy on prognosis of patients with synovial
sarcoma.
AB - BACKGROUND: This study aimed to explore the clinical efficacy of neoadjuvant
chemotherapy combined with surgery in primary synovial sarcoma of the limbs and
trunk through retrospective analysis of patients with primary synovial sarcoma of
the limbs and trunk treated by this treatment in our hospital. METHODS: A total
of 89 patients diagnosed with synovial sarcoma were enrolled in this study
between January 2005 and December 2011 in PLA General Hospital. Most of the
patients received neoadjuvant chemotherapy combined with operative treatment
(84.3%), 10.1% of them received adjuvant chemotherapy combined with operative
treatment, and only 5.6% received merely operative treatment. The influence on
the prognosis of patients with synovial sarcoma was analyzed by the statistics
overall survival (OS), progression-free survival (PFS), local control (LC), and
freedom from distant metastasis (FFDM). RESULTS: The median follow-up time was
68.6 months. The 5-year OS, 5-year PFS, 5-year LC, and 5-year FFDM of the
patients were 80.2, 60.5, 78.8, and 80.8%, respectively. The OS of the patients
with a tumor size >5 cm was lower (91.4 vs 73.1%, P < 0.05). Besides, the OS and
FFDM of neoadjuvant chemotherapy were better than those of adjuvant chemotherapy
(84.5 vs 55.6%, P = 0.015, and 83.8 vs 55.6%, P = 0.028, respectively). However,
there was no significant difference in the LC and PFS. CONCLUSIONS: Neoadjuvant
chemotherapy was beneficial for patients with synovial sarcoma, and it could
improve survival time and control distant metastasis. Tumor size was an important
factor influencing patients' prognosis.
PMID- 28494785
TI - Assessing pre- and postoperative activity levels with an accelerometer: a proof
of concept study.
AB - BACKGROUND: Postoperative recovery after abdominal surgery is measured mostly
based on subjective or self-reported data. In this article we aim to evaluate
whether recovery of daily physical activity levels can be measured
postoperatively with the use of an accelerometer. METHODS: In this multicenter,
observational pilot study, 30 patients undergoing laparoscopic abdominal surgery
(hysterectomy, adnexal surgery, cholecystectomy and hernia inguinal surgery) were
included. Patients were instructed to wear an Actigraph wGT3X-BT accelerometer
during one week before surgery (baseline) and during the first, third and fifth
week after surgery. Wear time, steps taken and physical activity intensity levels
(sedentary, light, moderate and vigorous) were measured. Patients were blinded
for the accelerometer outcomes. Additionally, an activity diary comprising
patients' self-reported time of being recovered and a list of 18 activities, in
which the dates of resumption of these 18 activities were recorded after surgery,
was completed by the patient. RESULTS: Five patients were excluded from analyses
because of technical problems with the accelerometer (n = 1) and protocol non
adherence (n = 4). Light, moderate, vigorous, combined moderate and vigorous
intensity physical activity (MVPA), and step counts showed a clear recovery curve
after surgery. Patients who underwent minor surgery reached their baseline step
count and MVPA three weeks after surgery. Patients who underwent intermediate
surgery had not yet reached their baseline step count during the last measuring
week (five weeks after surgery). The results of the activity diaries showed a
fair agreement with the accelerometer results (Cohens Kappa range: 0.273-0.391).
Wearing the accelerometer was well tolerated and not regarded as being burdensome
by the patients. CONCLUSIONS: The accelerometer appeared to be a feasible way to
measure recovery of postoperative physical activity levels in this study and was
well tolerated by the patients. The agreement with self-reported physical
recovery times was fair.
PMID- 28494787
TI - Missing heritability and where to find it.
AB - A report on the 11th Genomics of Rare Disease meeting held at the Wellcome Genome
Campus, Hinxton, Cambridge, UK, 5-7 April, 2017.
PMID- 28494786
TI - Compositionally and functionally distinct sinus microbiota in chronic
rhinosinusitis patients have immunological and clinically divergent consequences.
AB - BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized
by persistent sinonasal inflammation and sinus microbiome dysbiosis. The basis of
this heterogeneity is poorly understood. We sought to address the hypothesis that
a limited number of compositionally distinct pathogenic bacterial microbiota
exist in CRS patients and invoke discrete immune responses and clinical
phenotypes in CRS patients. RESULTS: Sinus brushings from patients with CRS (n =
59) and healthy individuals (n = 10) collected during endoscopic sinus surgery
were analyzed using 16S rRNA gene sequencing, predicted metagenomics, and RNA
profiling of the mucosal immune response. We show that CRS patients cluster into
distinct sub-groups (DSI-III), each defined by specific pattern of bacterial co
colonization (permutational multivariate analysis of variance (PERMANOVA); p =
0.001, r 2 = 0.318). Each sub-group was typically dominated by a pathogenic
family: Streptococcaceae (DSI), Pseudomonadaceae (DSII), Corynebacteriaceae
[DSIII(a)], or Staphylococcaceae [DSIII(b)]. Each pathogenic microbiota was
predicted to be functionally distinct (PERMANOVA; p = 0.005, r 2 = 0.217) and
encode uniquely enriched gene pathways including ansamycin biosynthesis (DSI),
tryptophan metabolism (DSII), two-component response [DSIII(b)], and the PPAR
gamma signaling pathway [DSIII(a)]. Each is also associated with significantly
distinct host immune responses; DSI, II, and III(b) invoked a variety of pro
inflammatory, TH1 responses, while DSIII(a), which exhibited significantly
increased incidence of nasal polyps (Fisher's exact; p = 0.034, relative risk =
2.16), primarily induced IL-5 expression (Kruskal Wallis; q = 0.045).
CONCLUSIONS: A large proportion of CRS patient heterogeneity may be explained by
the composition of their sinus bacterial microbiota and related host immune
response-features which may inform strategies for tailored therapy in this
patient population.
PMID- 28494788
TI - Comprehensive analysis of treatment response phenotypes in rheumatoid arthritis
for pharmacogenetic studies.
AB - BACKGROUND: An individual patient's response to a particular drug is influenced
by multiple factors, which may include genetic predisposition. Pharmacogenetic
studies attempt to discover and estimate the contributions of genetic variants to
the variability in response to a drug treatment. The task of identifying the
genetic contribution is often complicated by response phenotypes that are based
on imprecise or subjective clinical observations. Because the success of a
pharmacogenetic study depends on the analysis of a heritable phenotype, it is
important to identify phenotypes with a significant heritable component to ensure
reliable and reproducible results in subsequent genetic association studies.
METHODS: We retrospectively analyzed data collected from 436 rheumatoid arthritis
patients treated with golimumab during the phase III GO-FURTHER study. We
investigated the reliability of several potential response outcomes after
golimumab treatment. Using whole-genome sequencing of the clinical trial cohort,
we estimated the heritability of each potential outcome measure. We further
performed a longitudinal analysis of the clinical data to estimate variability of
outcome measures over time and the degree to which each response metric could be
confounded by placebo response. RESULTS: We determined that the high degree of
within-patient variation over time makes a single follow-up visit insufficient to
assess an individual patient's response to golimumab treatment. We found that
different potential response outcomes had varying degrees of heritability and
that averaging across multiple follow-up visits yielded higher heritability
estimates than single follow-up estimates. Importantly, we found that the change
in swollen and tender joint counts were the most heritable outcome metrics we
tested; however, we showed that they are also more likely to be confounded by a
placebo response than objective phenotypes like the change in C-reactive protein
levels. CONCLUSIONS: Our rigorous approach to finding robust and heritable
response phenotypes could be beneficial to all pharmacogenetic studies and may
lead to more reliable and reproducible results. TRIAL REGISTRATION:
Clinicaltrials.gov NCT00973479 . Registered 4 September 2009.
PMID- 28494789
TI - microRNAs: important regulators of stem cells.
AB - Stem cells are undifferentiated cells and have multi-lineage differentiation
potential. Generally, stem cells are classified into adult stem cells, embryonic
stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Stem cells have
great potential in clinical therapy due to their pluripotency and self-renewal
ability. microRNAs (miRNAs) are small non-coding RNAs which are evolutionarily
conserved and participate in the pathogenesis of many diseases, cell cycle
regulation, apoptosis, aging, cell fate decisions, and different signaling
pathways. Different kinds of stem cells possess distinct miRNA expression
profiles. Our review summarizes the critical roles of miRNAs in stem cell
reprogramming, pluripotency maintenance, and differentiation. In the future,
miRNAs may greatly contribute to stem cell clinical therapy and have potential
applications in regenerative medicine.
PMID- 28494790
TI - Erratum to: Keratinocyte growth factor in acute lung injury to reduce pulmonary
dysfunction - a randomised placebo-controlled trial (KARE): study protocol.
PMID- 28494791
TI - A cohort study examining emergency department visits and hospital admissions
among people who use drugs in Ottawa, Canada.
AB - BACKGROUND: The health of people who use drugs (PWUD) is characterized by
multimorbidity and chronicity of health conditions, necessitating an
understanding of their health care utilization. The objective of this study was
to evaluate emergency department (ED) visits and hospital admissions among a
cohort of PWUD. METHODS: We used a retrospective observational design between
2012 and 2013. The population was a marginalized cohort of PWUD (the PROUD study)
for whom survey data was linked (n = 663) to provincial health administrative
data housed at the Institute for Clinical Evaluative Sciences. We constructed a
5:1 comparison group matched by age, sex, income quintile, and region. The main
outcomes were defined as having two or more ED visits, or one or more hospital
admissions, in the year prior to survey completion. We used multivariable
logistic regression analyses to identify factors associated with these outcomes.
RESULTS: Compared to the matched cohort, PWUD had higher rates of ED visits (rate
ratio [RR] 7.0; 95% confidence interval [95% CI] 6.5-7.6) and hospitalization (RR
7.7; 95% CI 5.9-10.0). After adjustment, factors predicting more ED visits were
receiving disability (adjusted odds ratio [AOR] 3.0; 95% CI 1.7-5.5) or income
assistance (AOR 2.7; 95% CI 1.5-5.0), injection drug use (AOR 2.1; 95% CI 1.3
3.4), incarceration within 12 months (AOR 1.6; 95% CI 1.1-2.4), mental health
comorbidity (AOR 2.1; 95% CI 1.4-3.1), and a suicide attempt within 12 months
(AOR 2.1; 95% CI 1.1-3.4). Receiving methadone (AOR 0.5; 95% CI 0.3-0.9) and
having a regular family physician (AOR 0.5; 95% CI 0.2-0.9) were associated with
lower odds of having more ED visits. Factors associated with more hospital
admissions included Aboriginal identity (AOR 2.4; 95% CI 1.4-4.1), receiving
disability (AOR 2.4; 95% CI 1.1-5.4), non-injection drug use (opioids and non
opioids) (AOR 2.2; 95% CI 1.1-4.4), comorbid HIV (AOR 2.4; 95% CI 1.2-5.6),
mental health comorbidity (AOR 2.4; 95% CI 1.3-4.2), and unstable housing (AOR
1.9; 95% CI 1.0-3.4); there were no protective factors for hospitalization.
CONCLUSIONS: Improved post-incarceration support, housing services, and access to
integrated primary care services including opioid replacement therapy may be
effective interventions to decrease acute care use among PWUD, including targeted
approaches for people receiving social assistance or with mental health concerns.
PMID- 28494792
TI - Heterosis as a consequence of regulatory incompatibility.
AB - BACKGROUND: The merging of genomes in inter-specific hybrids can result in novel
phenotypes, including increased growth rate and biomass yield, a phenomenon known
as heterosis. Heterosis is typically viewed as the opposite of hybrid
incompatibility. In this view, the superior performance of the hybrid is
attributed to heterozygote combinations that compensate for deleterious mutations
accumulating in each individual genome, or lead to new, over-dominating
interactions with improved performance. Still, only fragmented knowledge is
available on genes and processes contributing to heterosis. RESULTS: We describe
a budding yeast hybrid that grows faster than both its parents under different
environments. Phenotypically, the hybrid progresses more rapidly through cell
cycle checkpoints, relieves the repression of respiration in fast growing
conditions, does not slow down its growth when presented with ethanol stress, and
shows increased signs of DNA damage. A systematic genetic screen identified
hundreds of S. cerevisiae alleles whose deletion reduced growth of the hybrid.
These growth-affecting alleles were condition-dependent, and differed greatly
from alleles that reduced the growth of the S. cerevisiae parent. CONCLUSIONS:
Our results define a budding yeast hybrid that is perturbed in multiple
regulatory processes but still shows a clear growth heterosis. We propose that
heterosis results from incompatibilities that perturb regulatory mechanisms,
which evolved to protect cells against damage or prepare them for future
challenges by limiting cell growth.
PMID- 28494793
TI - Real-time PCR assays for hepatitis B virus DNA quantification may require two
different targets.
AB - BACKGROUND: Quantification Hepatitis B virus (HBV) DNA plays a critical role in
the management of chronic HBV infections. However, HBV is a DNA virus with high
levels of genetic variation, and drug-resistant mutations have emerged with the
use of antiviral drugs. If a mutation caused a sequence mismatched in the primer
or probe of a commercial DNA quantification kit, this would lead to an
underestimation of the viral load of the sample. The aim of this study was to
determine whether commercial kits, which use only one pair of primers and a
single probe, accurately quantify the HBV DNA levels and to develop an improved
duplex real-time PCR assay. METHODS: We developed a new duplex real-time PCR
assay that used two pairs of primers and two probes based on the conserved S and
C regions of the HBV genome. We performed HBV DNA quantitative detection of HBV
samples and compared the results of our duplex real-time PCR assays with the
COBAS TaqMan HBV Test version 2 and Daan real-time PCR assays. The target region
of the discordant sample was amplified, sequenced, and validated using plasmid.
RESULTS: The results of the duplex real-time PCR were in good accordance with the
commercial COBAS TaqMan HBV Test version 2 and Daan real-time PCR assays. We
showed that two samples from Chinese HBV infections underestimated viral loads
when quantified by the Roche kit because of a mismatch between the viral sequence
and the reverse primer of the Roche kit. The HBV DNA levels of six samples were
undervalued by duplex real-time PCR assays of the C region because of mutations
in the primer of C region. CONCLUSIONS: We developed a new duplex real-time PCR
assay, and the results of this assay were similar to the results of commercial
kits. The HBV DNA level could be undervalued when using the COBAS TaqMan HBV Test
version 2 for Chinese HBV infections owing to a mismatch with the primer/probe. A
duplex real-time PCR assay based on the S and C regions could solve this problem
to some extent.
PMID- 28494794
TI - Juvenile idiopathic arthritis in relation to perinatal and maternal
characteristics: a case control study.
AB - BACKGROUND: Existing data on associations between maternal and early childhood
exposures and juvenile idiopathic arthritis (JIA) risk is scant and inconsistent
with previous studies showing potential role for prematurity, number of siblings
and infections. We explored JIA and International League of Associations for
Rheumatology (ILAR) JIA categories in relation to selected infant (birthweight,
size-for-gestational-age, gestational age), and maternal (parity, delivery type,
prior fetal loss) characteristics that may be markers for exposures related to
two pathways (hygiene hypothesis, microchimerism) potentially associated with
autoimmune disorder occurrence. METHODS: A case-control analysis with 1,234 JIA
cases and 5,993 birth year-matched controls was conducted. Exposure information
was obtained from WA state birth certificates. Multivariable logistic regression
was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI)
for associations with maternal and early life exposures for JIA and JIA
categories. RESULTS: Greater maternal parity was associated with a decreased OR
for JIA (most marked for persistent oligoarticular JIA, OR 0.32, 95% CI 0.15;
0.71, p for trend = 0.0001). Prior fetal loss (except for oligoarticular JIA) was
associated with an increased OR for JIA. Prematurity was associated with
increased risk of enthesitis related arthritis (OR 1.9, 95% CI: 1.3-2.9) and
rheumatoid factor positive polyarticular JIA (OR 2.2, 95% CI: 1.0-4.8).
CONCLUSIONS: We observed associations of selected maternal factors with JIA, some
of which varied across JIA categories. The findings of decreased ORs for JIA in
relation to greater maternal parity may be consistent with the hygiene and
microchimerism hypotheses. Future studies with biomarkers relevant to these
hypotheses will help elucidate any associations.
PMID- 28494795
TI - A bio-behavioral intervention to decrease intravaginal practices and bacterial
vaginosis among HIV infected Zambian women, a randomized pilot study.
AB - BACKGROUND: Intravaginal practices (IVP) (cleansing or introducing products
inside the vagina for hygiene, health or to please sexual partners) are common
among women with HIV. IVP increase the risk of developing bacterial Vaginosis
(BV), the most common genital infection associated with transmission of sexually
transmitted infections and HIV. This study tested a pilot intervention to reduce
IVP and BV in HIV infected women in Zambia. METHODS: One hundred twenty-eight HIV
infected women engaging in IVP were randomized to two conditions: enhanced
standard of care (n = 70) and experimental (n = 58) from May 1, 2013 to February
28, 2014. All participants received a brief educational counseling session on
discontinuation of IVP, and those with BV, were provided with medical treatment
for BV. Women in the experimental condition received an additional group-based,
culturally tailored intervention. Participants completed questionnaires assessing
sexual risk factors and IVP and were assessed for BV using Nugent criteria at
baseline, 6 months and 12 months. RESULTS: At 12-month, the proportion of self
reported use of IVPs decreased in the experimental condition: soap (28% vs. 47%);
cloth or a rag (19% vs. 38%); and traditional medicines (22% vs. 42%) (all p <
0.05)) compared with the enhanced standard of care condition. The prevalence of
BV at 6 and 12 months did not differ by study condition but averaging over study
condition, prevalence of BV decreased from 64.2% at baseline to 15.6% at 6 months
(p < 0.01) and to 23.6% at 12 months (p = 0.15). Using an enhanced standard of
care approach and an enhanced standard of care + a group intervention, IVP and BV
decreased over time, but the experimental condition had greater reduction in self
reported use of IVP. CONCLUSIONS: Future studies should address interventions in
communities with high burden of IVP, BV and HIV. Interventions that could be
administered during routine medical care and decrease IVP and BV are needed, and
should be considered part of women's health programs. TRIAL REGISTRATION NUMBER:
NCT03134924 (retrospectively registered 21st April 2017).
PMID- 28494796
TI - A malignant solitary fibrous tumour arising from the first lumbar vertebra and
mimicking an osteosarcoma: a case report.
AB - BACKGROUND: A solitary fibrous tumour (SFT) is an unusual neoplasm typically
found in soft tissues. Although SFTs can arise in the bones, they very rarely
arise in the vertebral arch. Here, we describe a case of a SFT that arose in the
vertebral arch of the first lumbar (L1) spinal vertebrae and mimicked
osteosarcoma. CASE PRESENTATION: A 49-year-old woman presented with a 2-month
history of lower back pain and a lumbar region mass. Magnetic resonance imaging
demonstrated a heterogeneously enhanced mass in the L1 vertebral arch. The
patient received neoadjuvant chemotherapy, followed by a surgical procedure
comprising an anterior spinal fusion and en bloc resection. Histologically, our
initial diagnosis was osteosarcoma. The postoperative course was uneventful, and
the patient received adjuvant chemotherapy. However, the tumour metastasised to
the lung 5 years after the first surgery, and a second surgery was performed for
lung tumour resection. The histology of the metastatic lung tumour appeared
similar to that of the malignant SFT, and the specimen from the first surgery was
re-examined. Immunohistochemically, the tumour was positive for STAT6. Reverse
transcription-polymerase chain reaction revealed a NAB2-STAT6 fusion gene, thus
confirming our final diagnosis of malignant SFT. The patient died of disease
progression 8 years after the first surgery; however, there was no evidence of
local recurrence. CONCLUSIONS: Malignant SFT in the vertebral arch is extremely
rare and very difficult to distinguish histologically an osteoid from lace-like
collagen. STAT6 immunostaining is useful for distinguishing malignant SFTs from
other neoplasms. Although it is difficult to completely resect a SFT arising from
the spine, we demonstrated the feasibility of an en bloc resection of spinal
tumours arising from posterior elements, without local recurrence.
PMID- 28494797
TI - AHNAK suppresses tumour proliferation and invasion by targeting multiple pathways
in triple-negative breast cancer.
AB - BACKGROUND: AHNAK, also known as desmoyokin, is a giant protein with the
molecular size of approximately 700 kDa and exerts diverse functions in different
types of cancer. RESULTS: In the present study, we demonstrated that AHNAK mRNA
levels were down-regulated in 7 out of 8 human breast cancer cell lines,
especially in triple - negative breast cancer (TNBC) cell lines. Moreover, in
patients with TNBC, the expression of AHNAK gene was inversely correlated with
the tumor status (P = 0.015), lymph node status (P < 0.001), lymph node (LN)
infiltration (P < 0.001) and TNM stage (P < 0.001). Moreover, down-regulated
AHNAK expression was considered an independent prognostic factor associated with
the poor survival of patients with TNBC. Overexpression of AHNAK in two TNBC cell
lines, MDA-MB-231 and BT549, suppressed the in vitro TNBC cell proliferation and
colony formation, and inhibited the in vivo TNBC xenograft growth and lung
metastasis. The tumor suppressing effect of AHNAK in TNBC was associated with the
AKT/MAPK signaling pathway and Wnt/beta-catenin pathway. Consistent results were
observed when AHNAK was knockdown in BT20 and MDA-MB-435 cells. CONCLUSIONS:
Taken together, our results suggest that AHNAK acts as a tumor suppressor that
negatively regulates TNBC cell proliferation, TNBC xenograft growth and
metastasis via different signaling pathways.
PMID- 28494798
TI - Androstenedione response to recombinant human FSH is the most valid predictor of
the number of selected follicles in polycystic ovarian syndrome: (a case-control
study).
AB - BACKGROUND: We aimed to test the hypothesis that the correlation of the changes
in the blood Androstenedione (A4) levels to the number of selected follicles
during ovulation induction with low-dose recombinant human follicle stimulating
hormone (rhFSH) is as strong as the correlation to changes in the blood Estradiol
(E2) levels in polycystic ovary syndrome (PCOS). METHODS: Prospective Case
control study conducted from October 2014 to January 2016. 61 non-PCOS control
(Group I) and 46 PCOS (Group II) patients treated with the chronic low-dose step
up protocosl with rhFSH. A4, E2, progesterone blood levels and follicular growth
were monitored.. Univariate and hierarchical multivariable analysis were
performed for age, BMI, HOMA-IR, A4 and E2 (with the number of selected follicles
as the dependent variable in both groups). ROC analysis was performed to define
threshold values for the significant determinants of the number of selected
follicles to predict cyle cancellations due to excessive ovarian response.
RESULTS: The control group (Group I) was comprised of 61 cycles from a group of
primary infertile non-PCOS patients, and the study group (Group II) of 46 cycles
of PCOS patients. The analysis revealed that the strongest independent predictor
of the total number of selected follicles in Group I was the E2(AUC) (B =
0.0006[0.0003-0.001]; P < 0.001); whereas for Group II, it was the A4 (AUC) (B =
0.114[0.04-0.25]; P = 0.01). Optimum thresholds for the A4 related parameters
were defined to predict excessive response within Group II were 88.7%, 3.1 ng/mL
and 5.4 ng*days for the percentage increase in A4, the maximum A4 value and area
under the curve values for A4, respectively. CONCLUSION: A4 response to low-dose
rhFSH in PCOS has a stronger association with the number of follicles selected
than the E2 reponse. A4 response preceding the E2 response is essential for
progressive follicle development. Monitoring A4 rather than E2 may be more
preemptive to define the initial ovarian response and accurate titration of the
rhFSH doses. TRIAL REGISTRATION: The study was registered as a prospective case
control study in the ClinicalTrials.gov registry with the identifier NCT02329483
.
PMID- 28494799
TI - A systematic review of electronic audit and feedback: intervention effectiveness
and use of behaviour change theory.
AB - BACKGROUND: Audit and feedback is a common intervention for supporting clinical
behaviour change. Increasingly, health data are available in electronic format.
Yet, little is known regarding if and how electronic audit and feedback (e-A&F)
improves quality of care in practice. OBJECTIVE: The study aimed to assess the
effectiveness of e-A&F interventions in a primary care and hospital context and
to identify theoretical mechanisms of behaviour change underlying these
interventions. METHODS: In August 2016, we searched five electronic databases,
including MEDLINE and EMBASE via Ovid, and the Cochrane Central Register of
Controlled Trials for published randomised controlled trials. We included studies
that evaluated e-A&F interventions, defined as a summary of clinical performance
delivered through an interactive computer interface to healthcare providers. Data
on feedback characteristics, underlying theoretical domains, effect size and risk
of bias were extracted by two independent review authors, who determined the
domains within the Theoretical Domains Framework (TDF). We performed a meta
analysis of e-A&F effectiveness, and a narrative analysis of the nature and
patterns of TDF domains and potential links with the intervention effect.
RESULTS: We included seven studies comprising of 81,700 patients being cared for
by 329 healthcare professionals/primary care facilities. Given the extremely high
heterogeneity of the e-A&F interventions and five studies having a medium or high
risk of bias, the average effect was deemed unreliable. Only two studies
explicitly used theory to guide intervention design. The most frequent
theoretical domains targeted by the e-A&F interventions included 'knowledge',
'social influences', 'goals' and 'behaviour regulation', with each intervention
targeting a combination of at least three. None of the interventions addressed
the domains 'social/professional role and identity' or 'emotion'. Analyses
identified the number of different domains coded in control arm to have the
biggest role in heterogeneity in e-A&F effect size. CONCLUSIONS: Given the high
heterogeneity of identified studies, the effects of e-A&F were found to be highly
variable. Additionally, e-A&F interventions tend to implicitly target only a
fraction of known theoretical domains, even after omitting domains presumed not
to be linked to e-A&F. Also, little evaluation of comparative effectiveness
across trial arms was conducted. Future research should seek to further unpack
the theoretical domains essential for effective e-A&F in order to better support
strategic individual and team goals.
PMID- 28494800
TI - Somatic extracts of Marshallagia marshalli downregulate the Th2 associated immune
responses in ovalbumin-induced airway inflammation in BALB/c mice.
AB - BACKGROUND: Recently the role of gastrointestinal nematodes in modulating the
immune responses in inflammatory and immune-mediated conditions such as allergy
and autoimmune diseases has been introduced. This is mainly due to the
suppressive effects of somatic and excretory secretory (ES) products of nematodes
on the immune responses. In this study, we evaluated the immunomodulatory
potentials of somatic products of Marshallagia marshalli, a gastrointestinal
nematodes of sheep, to suppress the immune-mediated responses in a murine model
of allergic airway inflammation. BALB/c mice were intraperitoneally (IP)
sensitized with ovalbumin (OVA)/Alum and then challenged with 1% OVA. Somatic
products of M. marshalli were administered during each sensitization. The effects
of somatic products on development of allergic airway inflammation were evaluated
by analyzing inflammatory cells recruitment, histopathological changes, cytokines
production (IL-4, IL-13, IL-10, TGF-beta) and serum antibody titers (IgG1,
IgG2a). RESULTS: Somatic products of M. marshalli were able to suppress the
induction of allergic airway inflammation in mice. Modulation of Th2 type
responses (IL-4, IL-13, IgG1) via upregulations of IL-10 and TGF-beta production
was observed after injection of somatic products of M. marshalli. In addition,
inflammatory cells infiltration and pathological disorders were significantly
diminished following administration of somatic products. CONCLUSIONS: Our data
raised the possibility that helminths could be a potential therapeutic candidate
to alleviate the inflammatory conditions in allergic asthma. According to these
results, we concluded that M. marshalli may contain immune-modulatory molecules
that attenuate allergic airway inflammation via induction of regulatory
cytokines. Further investigations are required to identify molecules that might
have potentials for development of novel therapeutic targets.
PMID- 28494801
TI - Spectral imaging toolbox: segmentation, hyperstack reconstruction, and batch
processing of spectral images for the determination of cell and model membrane
lipid order.
AB - BACKGROUND: Spectral imaging with polarity-sensitive fluorescent probes enables
the quantification of cell and model membrane physical properties, including
local hydration, fluidity, and lateral lipid packing, usually characterized by
the generalized polarization (GP) parameter. With the development of commercial
microscopes equipped with spectral detectors, spectral imaging has become a
convenient and powerful technique for measuring GP and other membrane properties.
The existing tools for spectral image processing, however, are insufficient for
processing the large data sets afforded by this technological advancement, and
are unsuitable for processing images acquired with rapidly internalized
fluorescent probes. RESULTS: Here we present a MATLAB spectral imaging toolbox
with the aim of overcoming these limitations. In addition to common operations,
such as the calculation of distributions of GP values, generation of pseudo
colored GP maps, and spectral analysis, a key highlight of this tool is reliable
membrane segmentation for probes that are rapidly internalized. Furthermore,
handling for hyperstacks, 3D reconstruction and batch processing facilitates
analysis of data sets generated by time series, z-stack, and area scan microscope
operations. Finally, the object size distribution is determined, which can
provide insight into the mechanisms underlying changes in membrane properties and
is desirable for e.g. studies involving model membranes and surfactant coated
particles. Analysis is demonstrated for cell membranes, cell-derived vesicles,
model membranes, and microbubbles with environmentally-sensitive probes Laurdan,
carboxyl-modified Laurdan (C-Laurdan), Di-4-ANEPPDHQ, and Di-4-AN(F)EPPTEA (FE),
for quantification of the local lateral density of lipids or lipid packing.
CONCLUSIONS: The Spectral Imaging Toolbox is a powerful tool for the segmentation
and processing of large spectral imaging datasets with a reliable method for
membrane segmentation and no ability in programming required. The Spectral
Imaging Toolbox can be downloaded from
https://uk.mathworks.com/matlabcentral/fileexchange/62617-spectral-imaging
toolbox .
PMID- 28494802
TI - Reducing depressive symptomatology with a smartphone app: study protocol for a
randomized, placebo-controlled trial.
AB - BACKGROUND: Depression has become one of the leading contributors to the global
disease burden. Evidence-based treatments for depression are available, but
access to them is still limited in some instances. As technology has become more
integrated into mental health care, computerized cognitive behavioral therapy
(CBT) protocols have become available and have been recently transposed to mobile
environments (e.g., smartphones) in the form of "apps." Preliminary research on
some depression apps has shown promising results in reducing subthreshold or mild
to moderate depressive symptoms. However, this small number of studies reports a
low statistical power and they have not yet been replicated. Moreover, none of
them included an active placebo comparison group. This is problematic, as a
"digital placebo effect" may explain some of the positive effects documented
until now. The aim of this study is to test a newly developed mobile app firmly
grounded in the CBT theory of depression to determine whether this app is
clinically useful in decreasing moderate depressive symptoms when compared with
an active placebo. Additionally, we are interested in the app's effect on
emotional wellbeing and depressogenic cognitions. METHODS/DESIGN: Romanian
speaking adults (18 years and older) with access to a computer and the Internet
and owning a smartphone are included in the study. A randomized, three-arm
clinical trial is being conducted (i.e., active intervention, placebo
intervention and delayed intervention). Two hundred and twenty participants with
moderate depressive symptoms (i.e., obtaining scores >9 and <=16 on the Patient
Health Questionnaire, PHQ-9) will be randomized to the three conditions.
Participants undergoing therapy, presenting serious mental health problems, or
legal or health issues that would prevent them from using the app, as well as
participants reporting suicidal ideation are excluded. Participants randomized to
the active and placebo interventions will use the smartphone app for 6 weeks. A
short therapist check-in via phone will take place every week. Participants in
the delayed-intervention condition will be given access to the app after 6 weeks
from randomization. The primary outcome is the level of depressive
symptomatology. The intervention delivered through the app to the active
condition includes psychoeducational materials and exercises based on CBT for
depression, while the placebo intervention uses a sham version of the app (i.e.,
similar structure of courses and exercises). DISCUSSION: To our knowledge, this
study protocol is the first to test the efficacy of a smartphone app for
depressive symptomatology in the form of a randomized controlled trial (RCT) that
includes an active placebo condition. As such, this can substantially add to the
body of evidence supporting the use of apps designed to decrease depression.
TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT03060200 . Registered on 1
February 2017. The first participant was enrolled on 17 February 2017.
PMID- 28494803
TI - Alzheimer's disease, dementia, and stem cell therapy.
AB - Alzheimer's disease (AD) represents arguably the most significant social,
economic, and medical crisis of our time. Characterized by progressive
neurodegenerative pathology, AD is first and foremost a condition of neuronal and
synaptic loss. Repopulation and regeneration of depleted neuronal circuitry by
exogenous stem cells is therefore a rational therapeutic strategy. This review
will focus on recent advances in stem cell therapies utilizing animal models of
AD, as well as detailing the human clinical trials of stem cell therapies for AD
that are currently undergoing development.
PMID- 28494804
TI - Validity of the posttraumatic stress disorders (PTSD) checklist in pregnant
women.
AB - BACKGROUND: The PTSD Checklist-civilian (PCL-C) is one of the most commonly used
self-report measures of PTSD symptoms, however, little is known about its
validity when used in pregnancy. This study aims to evaluate the reliability and
validity of the PCL-C as a screen for detecting PTSD symptoms among pregnant
women. METHODS: A total of 3372 pregnant women who attended their first prenatal
care visit in Lima, Peru participated in the study. We assessed the reliability
of the PCL-C items using Cronbach's alpha. Criterion validity and performance
characteristics of PCL-C were assessed against an independent, blinded Clinician
Administered PTSD Scale (CAPS) interview using measures of sensitivity,
specificity and receiver operating characteristics (ROC) curves. We tested
construct validity using exploratory and confirmatory factor analytic approaches.
RESULTS: The reliability of the PCL-C was excellent (Cronbach's alpha =0.90). ROC
analysis showed that a cut-off score of 26 offered optimal discriminatory power,
with a sensitivity of 0.86 (95% CI: 0.78-0.92) and a specificity of 0.63 (95% CI:
0.62-0.65). The area under the ROC curve was 0.75 (95% CI: 0.71-0.78). A three
factor solution was extracted using exploratory factor analysis and was further
complemented with three other models using confirmatory factor analysis (CFA). In
a CFA, a three-factor model based on DSM-IV symptom structure had reasonable fit
statistics with comparative fit index of 0.86 and root mean square error of
approximation of 0.09. CONCLUSION: The Spanish-language version of the PCL-C may
be used as a screening tool for pregnant women. The PCL-C has good reliability,
criterion validity and factorial validity. The optimal cut-off score obtained by
maximizing the sensitivity and specificity should be considered cautiously; women
who screened positive may require further investigation to confirm PTSD
diagnosis.
PMID- 28494806
TI - What makes weekend allied health services effective and cost-effective (or not)
in acute medical and surgical wards? Perceptions of medical, nursing, and allied
health workers.
AB - BACKGROUND: There is strong public support for acute hospital services to move to
genuine 7-day models, including access to multidisciplinary team assessment. This
study aimed to identify factors that might enable an effective and cost-effective
weekend allied health services on acute hospital wards. METHODS: This qualitative
study included 22 focus groups within acute wards with a weekend allied health
service and 11 telephone interviews with weekend service providers. Data were
collected from 210 hospital team members, including 17 medical, 97 nursing, and
96 allied health professionals from two Australian tertiary public hospitals. All
were recorded and imported into nVivo 10 for analysis. Thematic analysis methods
were used to develop a coding framework from the data and to identify emerging
themes. RESULTS: Key themes identified were separated into issues perceived as
being enablers or barriers to the effective or cost-effective delivery of weekend
allied health services. Perceived enablers of effectiveness and cost
effectiveness included prioritizing interventions that prevent decline, the right
person delivering the right service, improved access to the patient's family, and
ability to impact patient flow. Perceived barriers were employment of
inexperienced weekend staff, insufficient investment to see tangible benefit,
inefficiencies related to double-handling, unnecessary interventions and/or
inappropriate referrals, and difficulty recruiting and retaining skilled staff.
CONCLUSIONS: Suggestions for ensuring effective and cost effective weekend allied
health care models include minimization of task duplication and targeting
interventions so that the right patients receive the right interventions at the
right time. Further research into the effectiveness and cost effectiveness of
these services should factor in hidden costs, including those associated with
managing the service.
PMID- 28494805
TI - Relative incidence and individual-level severity of seasonal influenza A H3N2
compared with 2009 pandemic H1N1.
AB - BACKGROUND: Two subtypes of influenza A currently circulate in humans: seasonal
H3N2 (sH3N2, emerged in 1968) and pandemic H1N1 (pH1N1, emerged in 2009). While
the epidemiological characteristics of the initial wave of pH1N1 have been
studied in detail, less is known about its infection dynamics during subsequent
waves or its severity relative to sH3N2. Even prior to 2009, few data was
available to estimate the risk of severe outcomes following infection with one
circulating influenza strain relative to another. METHODS: We analyzed antibodies
in quadruples of sera from individuals in Hong Kong collected between July 2009
and December 2011, a period that included three distinct influenza virus
epidemics. We estimated infection incidence using these assay data and then
estimated rates of severe outcomes per infection using population-wide clinical
data. RESULTS: Cumulative incidence of infection was high among children in the
first epidemic of pH1N1. There was a change towards the older age group in the
age distribution of infections for pH1N1 from the first to the second epidemic,
with the age distribution of the second epidemic of pH1N1 more similar to that of
sH3N2. We found no serological evidence that individuals were infected in both
waves of pH1N1. The risks of excess mortality conditional on infection were
higher for sH3N2 than for pH1N1, with age-standardized risk ratios of 2.6 [95%
CI: 1.8, 3.7] for all causes and 1.5 [95% CI: 1.0, 2.1] for respiratory causes
throughout the study period. CONCLUSIONS: Overall increase in clinical incidence
of pH1N1 and higher rates of severity in older adults in post pandemic waves were
in line with an age-shift in infection towards the older age groups. The absence
of repeated infection is good evidence that waning immunity did not cause the
second wave. Despite circulating in humans since 1968, sH3N2 is substantially
more severe per infection than the pH1N1 strain. Infection-based estimates of
individual-level severity have a role in assessing emerging strains; updating
seasonal vaccine components; and optimizing of vaccination programs.
PMID- 28494807
TI - Concordant clear cell "mesonephric" carcinoma of the bladder and lung
adenocarcinoma with clear cell features - multiple primaries versus metastatic
neoplasms: a case report.
AB - BACKGROUND: Clear cell carcinoma of the bladder is a rare variant of urinary
bladder adenocarcinoma. We report a case of a patient with clear cell carcinoma
of the bladder and a concordant right upper lobe pulmonary adenocarcinoma with
clear cell features, and we address the role of immunohistochemistry and
cytogenetic analysis in distinguishing the two primary malignancies. CASE
PRESENTATION: Our patient was a 59-year-old African American woman who presented
with hematuria. Her past medical history included invasive mammary carcinoma and
end-stage renal disease treated with hemodialysis. A computed tomographic urogram
revealed a 3-cm polypoid bladder mass. A follow-up chest computed tomographic
scan revealed a 1-cm right upper lobe nodule. The patient underwent transurethral
biopsy and subsequent radical cystectomy, as well as a transthoracic core needle
biopsy of the lung nodule. Histologically, the bladder tumor consisted of flat,
cuboidal to columnar cells with clear or eosinophilic cytoplasm and a hobnail
appearance, organized in tubulocystic and papillary patterns. The neoplastic
cells were diffusely positive for alpha-methylacyl-coenzyme A racemase, cancer
antigen 125, and cytokeratin 7; focally positive for cytokeratin 20, P53, and
carcinoembryonic antigen; and negative for thyroid transcription factor 1. The
lung tumor demonstrated a glandular architecture with mucin production (positive
for mucin with mucicarmine and periodic acid-Schiff with diastase stain). The
neoplastic cells were diffusely positive for cytokeratin 7, napsin A, and thyroid
transcription factor 1, and they were negative for cytokeratin 20 and cancer
antigen 125. Genetic testing of the pulmonary neoplasm demonstrated ARID2 genomic
alterations. CONCLUSIONS: The presence of clear cell features in both neoplasms
raised the possibility of lung metastasis from the primary bladder tumor.
However, the glandular architecture of the lung neoplasm along with its
distinctive immunohistochemical and genetic profiles confirmed the presence of
two separate primaries.
PMID- 28494808
TI - Observational studies: goldmines of information on rare diseases.
AB - The article by Savina et al. from the large METASARC database of the French
Sarcoma Group (BMC Med 15:78, 2017) provides a wealth of information about the
natural history and therapy of patients with metastatic soft tissue sarcomas. The
information complements - and in some cases surpasses - that obtained from
randomized clinical trials, and should not be overlooked because of its
retrospective nature. For rare diseases, retrospective data are often more
important than data from randomized trials because of the inherent restrictions
on sample size. The article provides clear information regarding the different
behaviors of different histological types of sarcoma, the importance of localized
therapy for metastatic disease, and the critical role of combination chemotherapy
in initial treatment to improve survival.Please see related article:
https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0831-7.
PMID- 28494810
TI - Education and equipment for people who smoke crack cocaine in Canada: progress
and limits.
AB - BACKGROUND: People who smoke crack cocaine experience a wide variety of health
related issues. However, public health programming designed for this population
is limited, particularly in comparison with programming for people who inject
drugs. Canadian best practice recommendations encourage needle and syringe
programs (NSPs) to provide education about safer crack cocaine smoking practices,
distribute safer smoking equipment, and provide options for safer disposal of
used equipment. METHODS: We conducted an online survey of NSP managers across
Canada to estimate the proportions of NSPs that provide education and distribute
safer smoking equipment to people who smoke crack cocaine. We also assessed
change in pipe distribution practices between 2008 and 2015 in the province of
Ontario. RESULTS: Analysis of data from 80 programs showed that the majority
(0.76) provided education to clients on reducing risks associated with sharing
crack cocaine smoking equipment and about when to replace smoking equipment
(0.78). The majority (0.64) also distributed safer crack cocaine smoking
equipment and over half of these programs (0.55) had done so for less than 5
years. Among programs that distributed pipes, 0.92 distributed the recommended
heat-resistant Pyrex and/or borosilicate glass pipes. Only 0.50 of our full
sample reported that their program provides clients with containers for safer
disposal of used smoking equipment. The most common reasons for not distributing
safer smoking equipment were not enough funding (0.32) and lack of client demand
(0.25). Ontario-specific sub-analyses showed a significant increase in the
proportion of programs distributing pipes in Ontario from 0.15 (2008) to 0.71
(2015). CONCLUSIONS: Our findings point to important efforts by Canadian NSPs to
reduce harm among people who smoke crack cocaine through provision of education
and equipment, but there are still limits that could be addressed. Our study can
provide guidance for future cross-jurisdiction studies to describe relationships
involving harm reduction programs and provision of safer crack cocaine smoking
education and equipment.
PMID- 28494809
TI - The PED-t trial protocol: The effect of physical exercise -and dietary therapy
compared with cognitive behavior therapy in treatment of bulimia nervosa and
binge eating disorder.
AB - BACKGROUND: Sufferers from bulimia nervosa (BN) and binge eating disorder (BED)
underestimate the severity risk of their illness and, therefore, postpone seeking
professional help for years. Moreover, less than one in five actually seek
professional help and only 50% respond to current treatments, such as cognitive
behavioral therapy (CBT). The impetus for the present trial is to explore a novel
combination treatment approach adapted from physical exercise- and dietary
therapy (PED-t). The therapeutic underpinnings of these separate treatment
components are well-known, but their combination to treat BN and BED have never
been previously tested. The purpose of this paper is to provide the rationale for
this new treatment approach and to outline the specific methods and procedures.
METHODS: The PED-t trial uses a prospective randomized controlled design. It
allocates women between 18 and 40 years (BMI range 17.5-35.0) to groups
consisting of 5-8 members who receive either CBT or PED-t for 16 weeks. Excess
participants are allocated to a waiting list control group condition. All
participants are assessed at baseline, post-treatment, 6, 12 and 24 months' post
follow-up, respectively, and monitored for changes in biological, psychological
and therapy process variables. The primary outcome relates to the ED symptom
severity, while secondary outcomes relates to treatment effects on physical
health, treatment satisfaction, therapeutic alliance, and cost-effectiveness. We
aim to disseminate the results in high-impact journals, preferable open access,
and at international conferences. DISCUSSION: We expect that the new treatment
will perform equal to CBT in terms of behavioral and psychological symptoms, but
better in terms of reducing somatic symptoms and complications. We also expect
that the new treatment will improve physical fitness and thereby, quality of
life. Hence, the new treatment will add to the portfolio of evidence-based
therapies and thereby provide a good treatment alternative for females with BN
and BED. TRIAL REGISTRATION: Prospectively registered in REC the 16th of December
2013 with the identifier number 2013/1871 , and in Clinical Trials the 17th of
February 2014 with the identifier number NCT02079935 .
PMID- 28494811
TI - The association between implementation strategy use and the uptake of hepatitis C
treatment in a national sample.
AB - BACKGROUND: Hepatitis C virus (HCV) is a common and highly morbid illness. New
medications that have much higher cure rates have become the new evidence-based
practice in the field. Understanding the implementation of these new medications
nationally provides an opportunity to advance the understanding of the role of
implementation strategies in clinical outcomes on a large scale. The Expert
Recommendations for Implementing Change (ERIC) study defined discrete
implementation strategies and clustered these strategies into groups. The present
evaluation assessed the use of these strategies and clusters in the context of
HCV treatment across the US Department of Veterans Affairs (VA), Veterans Health
Administration, the largest provider of HCV care nationally. METHODS: A 73-item
survey was developed and sent to all VA sites treating HCV via electronic survey,
to assess whether or not a site used each ERIC-defined implementation strategy
related to employing the new HCV medication in 2014. VA national data regarding
the number of Veterans starting on the new HCV medications at each site were
collected. The associations between treatment starts and number and type of
implementation strategies were assessed. RESULTS: A total of 80 (62%) sites
responded. Respondents endorsed an average of 25 +/- 14 strategies. The number of
treatment starts was positively correlated with the total number of strategies
endorsed (r = 0.43, p < 0.001). Quartile of treatment starts was significantly
associated with the number of strategies endorsed (p < 0.01), with the top
quartile endorsing a median of 33 strategies, compared to 15 strategies in the
lowest quartile. There were significant differences in the types of strategies
endorsed by sites in the highest and lowest quartiles of treatment starts. Four
of the 10 top strategies for sites in the top quartile had significant
correlations with treatment starts compared to only 1 of the 10 top strategies in
the bottom quartile sites. Overall, only 3 of the top 15 most frequently used
strategies were associated with treatment. CONCLUSIONS: These results suggest
that sites that used a greater number of implementation strategies were able to
deliver more evidence-based treatment in HCV. The current assessment also
demonstrates the feasibility of electronic self-reporting to evaluate ERIC
strategies on a large scale. These results provide initial evidence for the
clinical relevance of the ERIC strategies in a real-world implementation setting
on a large scale. This is an initial step in identifying which strategies are
associated with the uptake of evidence-based practices in nationwide healthcare
systems.
PMID- 28494812
TI - Whole blood gene expression in adolescent chronic fatigue syndrome: an
exploratory cross-sectional study suggesting altered B cell differentiation and
survival.
AB - BACKGROUND: Chronic fatigue syndrome (CFS) is a prevalent and disabling condition
affecting adolescents. The pathophysiology is poorly understood, but immune
alterations might be an important component. This study compared whole blood gene
expression in adolescent CFS patients and healthy controls, and explored
associations between gene expression and neuroendocrine markers, immune markers
and clinical markers within the CFS group. METHODS: CFS patients (12-18 years
old) were recruited nation-wide to a single referral center as part of the
NorCAPITAL project. A broad case definition of CFS was applied, requiring 3
months of unexplained, disabling chronic/relapsing fatigue of new onset, whereas
no accompanying symptoms were necessary. Healthy controls having comparable
distribution of gender and age were recruited from local schools. Whole blood
samples were subjected to RNA sequencing. Immune markers were blood leukocyte
counts, plasma cytokines, serum C-reactive protein and immunoglobulins.
Neuroendocrine markers encompassed plasma and urine levels of catecholamines and
cortisol, as well as heart rate variability indices. Clinical markers consisted
of questionnaire scores for symptoms of post-exertional malaise, inflammation,
fatigue, depression and trait anxiety, as well as activity recordings. RESULTS: A
total of 29 CFS patients and 18 healthy controls were included. We identified 176
genes as differentially expressed in patients compared to controls, adjusting for
age and gender factors. Gene set enrichment analyses suggested impairment of B
cell differentiation and survival, as well as enhancement of innate antiviral
responses and inflammation in the CFS group. A pattern of co-expression could be
identified, and this pattern, as well as single gene transcripts, was
significantly associated with indices of autonomic nervous activity, plasma
cortisol, and blood monocyte and eosinophil counts. Also, an association with
symptoms of post-exertional malaise was demonstrated. CONCLUSION: Adolescent CFS
is characterized by differential gene expression pattern in whole blood
suggestive of impaired B cell differentiation and survival, and enhanced innate
antiviral responses and inflammation. This expression pattern is associated with
neuroendocrine markers of altered HPA axis and autonomic nervous activity, and
with symptoms of post-exertional malaise. Trial registration Clinical Trials
NCT01040429.
PMID- 28494814
TI - Erratum to: Analysis of necroptotic proteins in failing human hearts.
PMID- 28494815
TI - Association between fluid intake and mortality in critically ill patients with
negative fluid balance: a retrospective cohort study.
AB - BACKGROUND: Compared to positive fluid balance (FB), negative FB is associated
with improved clinical outcomes in critically ill patients. However, as to
whether achieving more negative FB can further improve outcomes has not been
investigated. This study aimed to investigate whether more negative FB and
restricted fluid intake were associated with improved outcomes in critically ill
patients. METHOD: Data were extracted from the Multi-parameter Intelligent
Monitoring in Intensive Care III Database. Patients achieving negative FB at 48
hours after intensive care unit (ICU) admission were screened. The primary
outcome was hospital mortality. Logistic models were built to explore the
association between FB, fluid intake and mortality, using FB and fluid intake
(both four levels) as design variables and using the linear spline function
method. RESULTS: There were 2068 patients meeting the inclusion criteria.
Compared to slight negative FB (level 1), there was a decreased tendency towards
mortality with FB level 2 (OR 0.88, 95% CI 0.69-1.11) and level 3 (OR 0.79, 95%
CI 0. 65-1.11); however, only extreme negative FB (level 4) was significant (OR
0.56, 95% CI 0. 33-0.95). Fluid intake and urine output were evenly distributed
over the first 48 hours after ICU admission. Fluid intake was inversely
associated with hospital mortality, with the OR decreased stepwise from level 2
(OR 0.73, 95% CI 0.56-0.96) to level 4 (OR 0.47, 95% CI 0.30-0.74), referred to
level 1. Urine output also showed a similar pattern. Diuretic use was associated
with higher mortality in both models. CONCLUSION: In critically ill patients with
negative FB, both increased fluid intake and urine output were associated with
decreased hospital mortality. However, compared to slight FB, achieving more
negative FB was not associated with reduced mortality.
PMID- 28494813
TI - Not only dominant, not only optic atrophy: expanding the clinical spectrum
associated with OPA1 mutations.
AB - BACKGROUND: Heterozygous mutations in OPA1 are a common cause of autosomal
dominant optic atrophy, sometimes associated with extra-ocular manifestations.
Few cases harboring compound heterozygous OPA1 mutations have been described
manifesting complex neurodegenerative disorders in addition to optic atrophy.
RESULTS: We report here three patients: one boy showing an early-onset
mitochondrial disorder with hypotonia, ataxia and neuropathy that was severely
progressive, leading to early death because of multiorgan failure; two unrelated
sporadic girls manifesting a spastic ataxic syndrome associated with peripheral
neuropathy and, only in one, optic atrophy. Using a targeted resequencing of 132
genes associated with mitochondrial disorders, in two probands we found compound
heterozygous mutations in OPA1: in the first a 5 nucleotide deletion, causing a
frameshift and insertion of a premature stop codon (p.Ser64Asnfs*7), and a
missense change (p.Ile437Met), which has recently been reported to have clinical
impact; in the second, a novel missense change (p.Val988Phe) co-occurred with the
p.Ile437Met substitution. In the third patient a homozygous mutation, c.1180G > A
(p.Ala394Thr) in OPA1 was detected by a trio-based whole exome sequencing
approach. One of the patients presented also variants in mitochondrial DNA that
may have contributed to the peculiar phenotype. The deleterious effect of the
identified missense changes was experimentally validated in yeast model. OPA1
level was reduced in available patients' biological samples, and a clearly
fragmented mitochondrial network was observed in patients' fibroblasts.
CONCLUSIONS: This report provides evidence that bi-allelic OPA1 mutations may
lead to complex and severe multi-system recessive mitochondrial disorders, where
optic atrophy might not represent the main feature.
PMID- 28494816
TI - A giant squamous cell carcinoma of the skin of the thoracic wall: a case report
and review of the literature.
AB - BACKGROUND: We report a case of a 48-year-old white woman who presented with a
huge cutaneous protruding tumor of the thoracic wall below her left breast. CASE
PRESENTATION: The lesion was excised with clear margins from the adjacent skin,
and subcutaneous tissue was left to heal with second intention. A histological
examination of the surgical specimen revealed a well-differentiated infiltrative
cutaneous squamous cell carcinoma. Our patient neglected to attend our
Oncological Department to receive chemotherapy. Today, 12 months after surgery,
she is alive and without evidence of disease recurrence. CONCLUSIONS: Cutaneous
squamous cell carcinoma can reach a huge size if left untreated. Surgery is the
primary mode of treatment, followed by chemotherapy if applicable.
PMID- 28494817
TI - Comparison of cognitive functioning as measured by the Ruff Figural Fluency Test
and the CogState computerized battery within the LifeLines Cohort Study.
AB - BACKGROUND: The Ruff Figural Fluency Test (RFFT; a pencil and paper test) and the
CogState (a computerized cognitive test battery) are well-validated and suitable
tests to evaluate cognitive functioning in large observational studies at the
population level. The LifeLines Cohort Study includes the RFFT as baseline
measurement and incorporated the CogState as replacement for the RFFT at follow
up. It is unknown how these two tests relate to each other. Therefore, the aim of
this study is to examine the correlation between the RFFT and the CogState and
the impact of demographic characteristics on this association. METHODS: A
subcohort of the LifeLines Cohort Study, a large population based cohort study,
participated in this study. Correlations between the RFFT and six subtasks of the
CogState were examined. Subgroup analyses were performed to investigate the
influence of age, education, and gender on the results. With sensitivity analyses
we investigated the influence of computer experience and (physical) impairments.
RESULTS: A total of 509 participants (mean age (SD): 53 years (14.6); range 18-87
years) participated in this study. All correlations between the RFFT and the
CogState were statistically significant (except for the correlation between the
RFFT error ratio and the CogState One Back Task), ranging from -0.39 to 0.28.
Stratifying the analyses for age, education, and gender did not substantially
affect our conclusions. Sensitivity analyses showed no substantial influence of
level of computer experience or (physical) impairments. CONCLUSIONS: Correlations
found in the present study were only weak to moderate, indicating that cognitive
functioning measured by the RFFT does not measure the same components of
cognitive functioning as six subtasks of the CogState. Computerized testing such
as the CogState may be very well suited for large cohort studies to assess
cognitive functioning in the general population and to identify cognitive changes
as early as possible, as it is a less time- and labor intensive tool.
PMID- 28494818
TI - Is there echinococcosis in West Africa? A refugee from Niger with a liver cyst.
AB - BACKGROUND: Italy is presently facing an increase in immigration from sub-Saharan
Africa through the Mediterranean Sea. Case reports of human cystic echinococcosis
(CE) have been reported from most sub-Saharan countries. Therefore, an increase
in the number of patients with CE coming from these areas in the Italian and
European centers for infectious diseases is expected. Unfortunately, the
epidemiology of CE in sub-Saharan countries is poorly known, which makes clinical
suspicion and diagnosis of such infection difficult in patients coming from these
areas. RESULTS: Here we report a case of hepatic CE in a patient from Niger who
arrived in Italy through Libya and visited in a Tropical Medicine referral center
in Northern Italy. The parasite was identified molecularly as the G6 "camel"
strain of Echinococcus granulosus (E. canadensis). The diagnosis and management
of a chronic and clinically complex infection like CE in such situation is
difficult. Only 40 cases of CE from Niger have been reported; of these, 75% had
extra-hepatic localization. To our knowledge, no strain characterization of human
isolates from Niger has been reported so far. The CE cyst of the patient was in
CE3a stage, indicating active transmission from the area in which the patient
came. However, prevalence data from Niger, and from any other country in West
Africa, are almost inexistent. CONCLUSIONS: We argue that population epidemiology
surveys with ultrasound are warranted in Sahelian countries, including Niger.
These studies could improve the knowledge of CE epidemiology, provide health
authorities with important information for public health interventions targeting
this zoonosis, and shed light on any difference between tissue tropism and
clinical manifestations caused by the different E. granulosus strains.
PMID- 28494819
TI - Mild Cognitive Impairment in Parkinson's Disease: Clustering and Switching
Analyses in Verbal Fluency Test.
AB - OBJECTIVES: Mild cognitive impairment is common in non-demented Parkinson disease
patients (PD-MCI) and is considered as a risk factor for dementia. Executive
dysfunction has been widely described in PD and the Verbal Fluency Tests (VFT)
are often used for executive function assessment in this pathology. The Movement
Disorder Society (MDS) published guidelines for PD-MCI diagnosis in 2012.
However, no investigation has focused on the qualitative analysis of VFT in PD
MCI. The aim of this work was to study the clustering and switching strategies in
VFT in PD-MCI patients. Moreover, these variables are considered as predictors
for PD-MCI diagnosis. METHODS: Forty-three PD patients and twenty normal controls
were evaluated with a neuropsychological protocol and the MDS criteria for PD-MCI
were applied. Clustering and switching analysis were conducted for VFT. RESULTS:
The percentage of patients diagnosed with PD-MCI was 37.2%. The Mann-Whitney U
test analysis showed that PD-MCI performed poorly in different cognitive measures
(digit span, Wisconsin Card Sorting Test, judgment of line orientation, and
comprehension test), compared to PD patients without mild cognitive impairment
(PD-nMCI). Phonemic fluency analyses showed that PD-MCI patients produced fewer
words and switched significantly less, compared to controls and PD-nMCI.
Concerning semantic fluency, the PD-MCI group differed significantly, compared to
controls and PD-nMCI, in switches. Discriminant function analyses and logistic
regression analyses revealed that switches predicted PD-MCI. CONCLUSIONS: PD-MCI
patients showed poor performance in VFT related to the deficient use of
production strategies. The number of switches is a useful predictor for incident
PD-MCI. (JINS, 2017, 23, 511-520).
PMID- 28494820
TI - Positive and Negative Consequences of Making Coffee among Breakfast Related
Irrelevant Objects: Evidence from MCI, Dementia, and Healthy Ageing.
AB - OBJECTIVES: Previous studies have reported impairments in activities of daily
living (ADL) performance in the presence of irrelevant but
physically/functionally related objects in dementia patients. The aim of the
present study was to increase our knowledge about the impact of the presence of
contextually related non-target objects on ADL execution in patients with multi
domain mild cognitive impairment (MCI) and dementia. METHODS: We compared ADL
execution in patients with MCI, dementia, and healthy elderly participants under
two experimental conditions: One in which the target objects were embedded with
contextually related non-target items that constituted the object set necessary
to complete two additional (but unrequired) ADL tasks related to the target task,
and a second, control condition where target objects were surrounded by isolated
objects (they never constituted a whole set needed to complete an alternative ADL
task). RESULTS: Separate analysis of ADL errors associated with the target task
versus errors involving the non-target objects revealed that, although the
presence of contextually related objects facilitated the accomplishment of the
target task, such a condition also led to errors involving the use of irrelevant
objects in dementia and MCI. CONCLUSIONS: The presence of contextually related
non-target items produces both positive and negative effects on ADL performance.
These types of non-target objects might help to cue the retrieval of the action
schema related to the target task, particularly in patients with MCI. In
contrast, the presence of these objects might also lead to distraction in
dementia and MCI. (JINS, 2017, 23, 481-492).
PMID- 28494821
TI - Abstracts for the 24th Annual Meeting of the American Society for Neural Therapy
and Repair.
PMID- 28494822
TI - Nursing: The Balance of Mind, Body, and Spirit.
PMID- 28494823
TI - An Introduction to Epigenetics.
AB - Epigenetics refers to the heritable information that is exclusive of DNA. Several
syndromes have been found to occur as the result of the process of epigenetics.
This process causes changes in the expression of genes, without changing the
actual DNA sequence. The factors influencing this process include both internal
and external triggers, leading to modulation of the epigenome through different
mechanisms. This article aims to describe how the process of epigenetics gives
rise to the multitude of possible syndromes seen in neonates. The article will
also discuss the role of assisted reproductive technology may play in epigenetic
changes when compared with the naturally conceived embryo.
PMID- 28494824
TI - Beckwith-Wiedemann Syndrome Review: A Guide for the Neonatal Nurse.
AB - Beckwith-Wiedemann syndrome (BWS) is the most common pediatric overgrowth
syndrome. Features characteristic of the BWS phenotype include both physical
attributes, such as macroglossia, abdominal wall defects, gigantism, nevus
flammeus, visceromegaly, and mid-face hypoplasia, as well as biochemical
abnormalities such as hypoglycemia. It is essential for the neonatal nurse to be
able to recognize BWS in the patient's early years of life because of the
increased frequency of medical complications, malformations, and the increased
risk of embryonic malignancies. This article focuses on the presentation of BWS
as an aid to early detection.
PMID- 28494825
TI - Prader-Willi Syndrome: Background and Management.
AB - The imprinting disorder, Prader-Willi syndrome, is a condition associated with
the gene region 15q11.2-q.13. The phenotype includes multiple characteristics,
most of which are endocrine-related. An accurate diagnosis is done mostly through
pre- or postnatal genetic testing. Management is mainly aimed at correcting the
endocrine dysfunctions present in these patients. Genetic testing is also
important to distinguish between the different causes and to calculate the
recurrence risk for parents with affected children. Although a lot has been
discovered and this syndrome can be managed to a satisfactory degree, further
research is still important especially regarding new potential treatments with
greater efficiency and reduced invasiveness. The neonatal nurse has an important
role because the management requires thorough monitoring as well as high
compliance from both the patient and the carers. Thus, it is essential for the
neonatal nurse to have a good knowledge of this condition.
PMID- 28494826
TI - Angelman Syndrome: Identification and Management.
AB - Angelman syndrome (AS) is a neurobehavioral and genetically determined condition,
which affects approximately 1 in 15,000 individuals. It is caused by various
genetic mutations and deletions of the maternally-inherited UBE3A gene, on the
15q11-13 chromosomal region. The UBE3A gene, which encodes E3 ubiquitin ligase,
shows tissue-specific imprinting, being expressed entirely from the maternal
allele.The diagnosis of AS is confirmed either by methylation test or by mutation
analysis. A more severe clinical picture is linked with the deletion
phenotype.Patients with AS have a behavioral and motor pattern defined as "happy
puppet" because it is characterized by puppet-like ataxic jerky movements; a
happy, sociable disposition; and paroxysms of laughter. There is currently no
cure for AS, and management is mainly symptomatic. Novel therapeutic options are
directed toward the possibility of activating the silenced paternal copy of the
UBE3A gene.
PMID- 28494827
TI - Use of Placental/Umbilical Blood Sampling for Neonatal Admission Blood Cultures:
Benefits, Challenges, and Strategies for Implementation.
AB - Placental blood remains an underused resource for early neonatal care despite
ample evidence that placental blood provides the same clinical decision making
information without the need for painful, invasive blood sampling procedures.
Potential benefits of placental/umbilical blood sampling (PUBS) for neonatal
admission labs include decreases in pain reactivity, rates of anemia, need for
blood transfusions, use of vasopressors, and rates of intraventricular
hemorrhage. Here, we present a unique case study of a critically ill infant with
contradictory blood culture results from PUBS and direct infant sampling. A
negative admission direct sample blood culture result compared with a positive
admission PUBS blood culture result suggests that infection may have been missed
in the direct infant sample. Relevant placental embryology and circulation is
also described, as well as the benefits of PUBS for neonatal admission labs (with
focus on the blood culture), challenges associated with PUBS practice, and
strategies for implementation of PUBS.
PMID- 28494829
TI - Faith's Lodge: A Place of Peace for NICU Families in Grief or in Complex Health
Situations.
AB - Parents confronting the death of a child or working through the complex health
needs of a child often feel isolated in their communities. They seek a personal
connection with others who are going through similar emotions. Faith's Lodge is a
unique respite for those families to find a place to reflect, find peace, and
more.
PMID- 28494830
TI - Continuing Education Course.
PMID- 28494828
TI - Treatment of Persistent Pulmonary Hypertension of the Newborn: Use of Pulmonary
Vasodilators in Term Neonates.
AB - Persistent pulmonary hypertension of the newborn (PPHN) represents a challenging
condition associated with significant morbidity. A successful transition from
intrauterine to extrauterine life is contingent on adequate pulmonary
vasodilation. Several pathophysiologies contribute to the failure of this cascade
and may result in life-threatening hypoxia and acidosis in the newborn.
Management includes optimal respiratory support, adequate sedation and analgesia,
and support of vascular tone and cardiac function. Pulmonary vasodilation has the
potential to overcome the cycle of hypoxia and acidosis, improving outcome in
these infants. Oxygen and inhaled nitric oxide represent the foundation of
therapy. Tertiary pulmonary vasodilators represent a greater challenge, selecting
between therapies that include prostanoids, sildenafil, and milrinone. Variable
levels of evidence exist for each agent. Thorough review of available data
informing efficacy and adverse effects contributes to the development of an
informed approach to neonates with refractory PPHN.
PMID- 28494831
TI - News of the Academy of Neonatal Nursing.
PMID- 28494834
TI - Prediction of 10-year Atherosclerotic Cardiovascular Disease Risk among Adults
Aged 40-79 Years in China: a Nationally Representative Survey.
AB - OBJECTIVE: To establish the distribution of 10-year atherosclerotic
cardiovascular disease (ASCVD) risk among Chinese adults. METHODS: We estimated
the 10-year ASCVD risk by applying the 2013 American College of Cardiology/
American Heart Association pooled cohort equations (PCEs) to the data obtained
from the 2010 China Chronic Disease and Risk Factor Surveillance that involved
61,541 participants (representing 520,158,652 Chinese adults) aged 40-79 years.
We also compared the ASCVD risk with the 10-year ischemic cardiovascular disease
(ICVD) risk, which was calculated using the simplified scoring tables recommended
by the Chinese Guidelines for Prevention of Cardiovascular Diseases (Chinese
model). RESULTS: Based on the PCEs, the average 10-year ASCVD risk among adults
without self-reported stroke or myocardial infraction was 12.5%. Approximately
247 million (47.4%) and 107 million (20.6%) adults had ? 7.5% and > 20% 10-year
ASCVD risks, respectively. The 10-year ASCVD risk > 20% was higher among men,
less educated individuals, smokers, drinkers, and physically inactive individuals
than among their counterparts. Overall, 29.0% of adults categorized using the
Chinese model were overclassified with the PCEs. CONCLUSION: Our results define
the distribution of 10-year ASCVD risk among Chinese adults. The 10-year ASCVD
risk predicted by the PCEs was higher than the ICVD risk predicted by the Chinese
model.
PMID- 28494833
TI - Impact of Smoking Status on Lipoprotein Subfractions: Data from an Untreated
Chinese Cohort.
AB - OBJECTIVE: Cigarette smoking is one of the established risk factors of
atherosclerotic cardiovascular disease, however, its impact on lipids is not
completely understood, especially in the Chinese population. Therefore, this
study evaluated the impact of smoking status (non, former, and current smoking)
on the distribution of lipoprotein subfractions in untreated patients with angina
like chest pain. METHODS: A total of 877 patients were consecutively enrolled and
divided into nonsmoking (n = 518), former smoking (n = 103), and current smoking
(n = 256) groups. Both low- and high-density lipoprotein cholesterol (LDL-C and
HDL-C) subfractions were measured using the Quantimetrix Lipoprint System. The
distributions of lipoprotein subfractions were evaluated among the groups.
RESULTS: Compared with nonsmoking subjects, the current smoking group had
significantly lower large/medium HDL-C (both P < 0.001) concentration and large
HDL subfraction percentage but higher small HDL-C and medium LDL-C concentrations
as well as medium LDL subfraction percentage. Importantly, former smoking
subjects showed elevated levels of large HDL-C concentration, large HDL particle
percentage, and mean LDL particle size and attenuation in small HDL/LDL
percentages and small LDL-C concentration, but these levels did not reach the
optimal status compared with those of the non-smoking group (data not shown).
CONCLUSION: Smoking has an adverse impact on the lipoprotein subfractions,
presented as lower large HDL particles besides higher small HDL and medium LDL
particles, whereas smoking cessation could reverse these change to a certain
degree.
PMID- 28494835
TI - Validation of the Simplified Chinese-character Version of the International
Physical Activity Questionnaire-Long Form in Urban Community-dwelling Adults: a
Cross-sectional Study in Hangzhou, China.
AB - OBJECTIVE: To assess the test-retest reliability and criterion validity of the
Simplified Chinese-character version of the International Physical Activity
Questionnaire Long form (IPAQ-L) in urban community-dwelling adults in Hanghzou,
China. METHODS: A total of 158 eligible participants aged 25-59 years from 6
neighbourhoods in two central districts of Hangzhou completed the IPAQ-L
questionnaire twice within a 7-day interval. Half of the subjects wore pedometers
during the first 7 days. Test-retest reliability was examined by comparing the
first (Day 1) and the second (Day 9) survey of IPAQ-L. Criterion validity was
assessed by comparing IPAQ-L with pedometer data. RESULTS: Modest to good test
retest reliability was found with intraclass correlation coefficients of 0.67 for
total PA, 0.37 to 0.73 for specific dimensions, and 0.56 to 0.71 for different
intensities of PA. Total PA measured by IPAQ-L was moderately correlated with
exercise levels (partial r = 0.27, P = 0.020) and walking distance (partial r =
0.31, P = 0.007), which were measured by a pedometer, after adjusting for gender,
age, educational attainment and employment status. CONCLUSION: Our results
indicate that the IPAQ-L is a reliable and validated measure for assessing
physical activity levels in this population and possibly the adult population in
other mainland Chinese cities.
PMID- 28494836
TI - Pulmonary Toxicity in Rats Caused by Exposure to Intratracheal Instillation of
SiO2 Nanoparticles.
AB - OBJECTIVE: The effect of the silica nanoparticles (SNs) on lungs injury in rats
was investigated to evaluate the toxicity and possible mechanisms for SNs.
METHODS: Male Wistar rats were instilled intratracheally with 1 mL of saline
containing 6.25, 12.5, and 25.0 mg of SNs or 25.0 mg of microscale SiO2 particles
suspensions for 30 d, were then sacrificed. Histopathological and ultrastructural
change in lungs, and chemical components in the urine excretions were
investigated by light microscope, TEM and EDS. MDA, NO and hydroxyproline (Hyp)
in lung homogenates were quantified by spectrophotometry. Contents of TNF-alpha,
TGF-beta1, IL-1beta, and MMP-2 in lung tissue were determined by
immunohistochemistry staining. RESULTS: There is massive excretion of Si
substance in urine. The SNs lead pulmonary lesions of rise in lung/body
coefficients, lung inflammation, damaged alveoli, granuloma nodules formation,
and collagen metabolized perturbation, and lung tissue damage is milder than
those of microscale SiO2 particles. The SNs also cause increase lipid
peroxidation and high expression of cytokines. CONCLUSION: The SNs result into
pulmonary fibrosis by means of increase lipid peroxidation and high expression of
cytokines. Milder effect of the SNs on pulmonary fibrosis comparing to microscale
SiO2 particles is contributed to its elimination from urine due to their
ultrafine particle size.
PMID- 28494837
TI - The Association between the C5263T Mutation in the Mitochondrial ND2 Gene and
Coronary Heart Disease among Young Chinese Han People.
AB - OBJECTIVE: This study aimed to investigate the genetic background of
mitochondrial genes in young patients with Coronary heart disease (CHD) to
provide a foundation for the early prevention of young patients with CHD.
METHODS: 115 cases of young (? 45 years) CHD Chinese Han patients (case group),
100 cases of older (> 45 years) Chinese Han CHD patients (experimental group)
hospitalized and 100 cases of healthy people through physical examination
(control group) at the General Hospital of PLA between January 2014 and December
2015 were selected. General information, clinical assessment, pedigree analysis,
and mitochondrial full sequence scanning were performed. The pedigrees of one
patient harbouring the C5263T mutation were recruited. Mitochondrial functional
analysis including cellular reactive oxygen species (ROS) levels and
mitochondrial membrane potential (MMP) were performed on pedigrees with the
C5263T mutation (mutation group) and without the mutation (non-mutation group).
RESULTS: The differences in biochemical tests (P > 0.05) between the case group
and experimental group were not significant. The C5263T single-nucleotide
mutation of the mitochondrial ND2 gene was observed in 2 young CHD patients in
the case group. The premature CHD of these 2 patients followed a pattern of
maternal inheritance. The mutation group (I1, II2) had higher ROS levels (4750.82
+/- 1045.55 vs. 3888.58 +/- 487.60, P = 0.022) and lower MMP levels (P = 0.045)
than the non-mutation group (II1, III1, III2). CONCLUSION: We speculated that the
mitochondrial C5263T mutation might be associated with the occurrence CHD in
Chinese Han young people.
PMID- 28494838
TI - Association between the SUMO4 M55V Polymorphism and Susceptibility to Type 2
Diabetes Mellitus: A Meta-analysis.
AB - OBJECTIVE: The aim of this study is to determine whether the SUMO4 M55V
polymorphism is associated with susceptibility to type 2 diabetes mellitus
(T2DM). METHODS: A meta-analysis was performed to detect the potential
association of the SUMO4 M55V polymorphism and susceptibility to T2DM under
dominant, recessive, co-dominant (homogeneous and heterogeneous), and additive
models. RESULTS: A total of eight articles including 10 case-control studies,
with a total of 2932 cases and 2679 controls, were included in this meta
analysis. The significant association between the SUMO4 M55V polymorphism and
susceptibility to T2DM was observed in the dominant model (GG + GA versus AA: OR
= 1.21, 95% CI = 1.05-1.40, P = 0.009), recessive model (GG versus GA + AA: OR =
1.29, 95% CI = 1.07-1.356, P = 0.010), homozygous model (GG versus AA: OR = 1.41,
95% CI = 1.06-1.56, P = 0.001), and additive model (G versus A: OR = 1.18, 95% CI
= 1.08-1.29, P = 0.001), and marginally significant in the heterozygous model (GA
versus AA: OR = 1.16, 95% CI = 0.98-1.36, P = 0.080). In subgroup analyses,
significant associations were observed in the Chinese population under four
genetic models excluding the heterozygous model, whereas no statistically
significant associations were observed in the Japanese population under each of
the five genetic models. CONCLUSION: The meta-analysis demonstrated that the G
allele of the SUMO4 M55V polymorphism could be a susceptible risk locus to T2DM,
mainly in the Chinese population, while the association in other ethnic
population needs to be further validated in studies with relatively large
samples.
PMID- 28494839
TI - Hexabromocyclododecane-induced Genotoxicity in Cultured Human Breast Cells
through DNA Damage.
AB - To investigate the genotoxicity and reveal the potential toxicological mechanisms
of Hexabromocyclododecane (HBCD), human breast cells HBL-100 were exposed to a
sequence of HBCD concentrations (0, 5, 10, and 50 mg/L) for 24 h. With a series
of zymology and molecular biology methods, we found that HBCD induced dose
dependent oxidative stress on HBL-100 DNA. As revealed in qRT-PCR, activated
prognostic factor ATM down-regulated tumor suppressor gene BRCA1 and prompted DNA
repair genes hOGG1 and hMTH1 expression in lower concentrations of HBCD (< 10
mg/L). However, DNA repair were inhibited as well as cell proliferation rate by
higher concentrations of HBCD (50 mg/L). The results inferred that the
genotoxicity of HBCD was dose-dependent and related to DNA repair pathway.
PMID- 28494840
TI - Differential Proteomics Reveals the Potential Injury Mechanism Induced by Heavy
Ion Radiation in Mice Ovaries.
AB - In the present study, we used a proteomics approach based on a two-dimensional
electrophoresis (2-DE) reference map to investigate protein expression in the
ovarian tissues of pubertal Swiss-Webster mice subjected to carbon ion radiation
(CIR). Among the identified proteins, ubiquitin carboxy-terminal hydrolase L1
(UCH-L1) is associated with the cell cycle[1] and that it influences
proliferation in ovarian tissues. We analyzed the expression of UCH-L1 and the
proliferation marker proliferation cell nuclear antigen (PCNA) following CIR
using immunoblotting and immunofluorescence. The proteomics and biochemical
results provide insight into the underlying mechanisms of CIR toxicity in ovarian
tissues.
PMID- 28494841
TI - Quercetin Attenuates Benzo(alpha)pyrene-induced CYP1A Expression.
AB - We studied effects of nutrient quercetin on cytochromes' R450 1A (CYP1A)
activities (measured spectrofluorimetrically using 7-ethoxy-resorufin for CYP1A1
and 7-methoxy-resorufin for CYP1A2 as substrates), on mRNA levels (measured by RT
PCR), and on DNA-binding activities (evaluated by an electrophoretic mobility
shift assay) of proteins regulating CYP1A expression in untreated and
benzo(alpha)pyrene (BaP)-treated rats. Wistar rats received quercetin, BaP, or
both once daily for 1-3 days. Quercetin did not influence CYP1A1 in untreated
rats but inhibited BaP-mediated CYP1A induction on the transcriptional level
decreasing positive input (AhR functional activity) and increasing negative input
(AhRR/ARNT expression and Oct-1 and C/EBP functional activities).
PMID- 28494842
TI - Two consecutive large outbreaks of Salmonella Muenchen linked to pig farming in
Germany, 2013 to 2014: Is something missing in our regulatory framework?
AB - In 2013, raw pork was the suspected vehicle of a large outbreak (n = 203 cases)
of Salmonella Muenchen in the German federal state of Saxony. In 2014, we
investigated an outbreak (n = 247 cases) caused by the same serovar affecting
Saxony and three further federal states in the eastern part of Germany. Evidence
from epidemiological, microbiological and trace-back investigations strongly
implicated different raw pork products as outbreak vehicles. Trace-back analysis
of S. Muenchen-contaminated raw pork sausages narrowed the possible source down
to 54 pig farms, and S. Muenchen was detected in three of them, which traded
animals with each other. One of these farms had already been the suspected source
of the 2013 outbreak. S. Muenchen isolates from stool of patients in 2013 and
2014 as well as from food and environmental surface swabs of the three pig farms
shared indistinguishable pulsed-field gel electrophoresis patterns. Our results
indicate a common source of both outbreaks in the primary production of pigs.
Current European regulations do not make provisions for Salmonella control
measures on pig farms that have been involved in human disease outbreaks. In
order to prevent future outbreaks, legislators should consider tightening
regulations for Salmonella control in causative primary production settings.
PMID- 28494843
TI - Passive enhanced safety surveillance for Vaxigrip and Intanza 15 ug in the United
Kingdom and Finland during the northern hemisphere influenza season 2015/16.
AB - Enhanced safety surveillance (ESS) was conducted in the United Kingdom and
Finland for Vaxigrip and Intanza 15 ug to comply with the European Medicines
Agency interim guidance aimed to detect any potential increase in reactogenicity
in near real time following the annual update of the influenza vaccine strain
composition. This pilot passive ESS was established to strengthen safety
monitoring by facilitating spontaneous vaccinee reports and estimating near real
time vaccinee exposure. The primary objective was to estimate the reporting rates
of suspected adverse reactions (ARs) occurring within 7 days post vaccination
during the northern hemisphere 2015/16 influenza season. Among the Vaxigrip
vaccinees (n = 1,012), 32 (3.2%) reported a total of 122 suspected ARs, including
110 suspected ARs that occurred within 7 days post vaccination. Among the Intanza
15 ug vaccinees (n = 1,017), 31 (3.0%) reported a total of 114 suspected ARs,
including 99 that occurred within 7 days post-vaccination. These results were
consistent with the known safety profile of the two vaccines and did not show any
change in reactogenicity or safety concerns. This passive ESS showed improved
data reporting and demonstrated its suitability to health authorities'
requirements; further fine tuning of the methodology is under discussion between
all stakeholders.
PMID- 28494844
TI - West Nile virus surveillance in Europe: moving towards an integrated animal-human
vector approach.
AB - This article uses the experience of five European countries to review the
integrated approaches (human, animal and vector) for surveillance and monitoring
of West Nile virus (WNV) at national and European levels. The epidemiological
situation of West Nile fever in Europe is heterogeneous. No model of surveillance
and monitoring fits all, hence this article merely encourages countries to
implement the integrated approach that meets their needs. Integration of
surveillance and monitoring activities conducted by the public health
authorities, the animal health authorities and the authorities in charge of
vector surveillance and control should improve efficiency and save resources by
implementing targeted measures. The creation of a formal interagency working
group is identified as a crucial step towards integration. Blood safety is a key
incentive for public health authorities to allocate sufficient resources for WNV
surveillance, while the facts that an effective vaccine is available for horses
and that most infected animals remain asymptomatic make the disease a lesser
priority for animal health authorities. The examples described here can support
other European countries wishing to strengthen their WNV surveillance or
preparedness, and also serve as a model for surveillance and monitoring of other
(vector-borne) zoonotic infections.
PMID- 28494845
TI - Monitoring influenza virus susceptibility to oseltamivir using a new rapid assay,
iART.
AB - A new rapid assay for detecting oseltamivir resistance in influenza virus, iART,
was used to test 149 clinical specimens. Results were obtained for 132, with iART
indicating 41 as 'resistant'. For these, sequence analysis found known and
suspected markers of oseltamivir resistance, while no such markers were detected
for the remaining 91 samples. Viruses isolated from the 41 specimens showed
reduced or highly reduced inhibition by neuraminidase inhibition assay. iART may
facilitate broader antiviral resistance testing.
PMID- 28494846
TI - Can a science-based definition of acupuncture improve clinical outcomes?
AB - Research on acupuncture has been muddled by attempts to bridge the ancient with
the modern. Barriers to effectiveness research are reflected in recurring
conflicts that include disagreement on use of the most basic terms, lack of
standard intervention controls, and the absence of functional measures for
assessing treatment effect. Acupuncture research has stalled at the "placebo
barrier" wherein acupuncture is "no better than placebo." The most widely
recognized comparative effectiveness research in acupuncture does not compare
acupuncture treatment protocols within groups, thereby, mutating large scale
effectiveness studies into large scale efficacy trials. Too often research in
acupuncture attempts to tie outcomes to traditional belief systems thereby
limiting usefulness of the research. The acupuncture research paradigm needs to
focus more closely on a scientific definition of treatments and outcomes that
compare protocols in terms of prevalent clinical issues such as relative
effectiveness for treating pain.
PMID- 28494847
TI - History of cupping (Hijama): a narrative review of literature.
AB - Cupping (Hijama in Arabic) is an ancient, holistic method for the treatment of a
variety of diseases. Though the exact origin of cupping therapy is a matter of
controversy, its use has been documented in early Egyptian and Chinese medical
practices. Diverse human civilizations have contributed to the historical
development and continuation of cupping therapy. This narrative review describes
the history of cupping, historical definitions, cupping instruments and uses of
cupping therapy. Electronic searches of relevant databases (PubMed, Google
Scholar and OvidSP) were conducted using keywords and Boolean operators. Manual
searches and references of published articles and books were also conducted. A
number of articles (N = 625) were retained for extensive review, and finally 83
articles were included in this paper. The historical descriptions of cupping
therapy were found in ancient human civilizations of the Eastern and Western
world. There were inconsistent data concerning the origin of cupping,
definitions, instruments, procedures, definite advancements and research in
Hijama over centuries. Cupping therapy fell out of favor in 17th and mid-18th
centuries but recovered popularity in modern medicine. Currently, cupping therapy
is used for health promotion, prophylaxis and treatment of a variety of diseases
around the world. Cupping therapy with a good safety profile has a checkered
history and is a well-recognized traditional method for managing medical
conditions. Currently, the scope of cupping therapy is expanding, and a growing
body of research is providing additional evidence-based data for the further
advancement of cupping therapy in the treatment of a variety of diseases.
PMID- 28494848
TI - Standards of Reporting Kampo Products (STORK) in research articles.
AB - There had been no standardized rules for citing ethical Kampo products used in
clinical trials in journal articles. Although the name of a Kampo manufacturer
was described in 77.9% of research articles, the name and ratios of crude drug
components of Kampo formulas were not described in 77.5% of these papers.
Considering the importance of proper characterization of interventions in the
Consolidated Standards of Reporting Trials (CONSORT) checklist, we hereby propose
the use of the Standards of Reporting Kampo Products (STORK) website,
http://mpdb.nibiohn.go.jp/stork, as a reference for Kampo products. This will
provide an official source on the internet for verified information on individual
Kampo formulations for citation purposes in clinical research articles.
PMID- 28494849
TI - Identification and classification of traditional Chinese medicine syndrome types
among senior patients with vascular mild cognitive impairment using latent tree
analysis.
AB - OBJECTIVE: To treat patients with vascular mild cognitive impairment (VMCI) using
traditional Chinese medicine (TCM), it is necessary to classify the patients into
TCM syndrome types and to apply different treatments to different types. In this
paper, we investigate how to properly carry out the classification for patients
with VMCI aged 50 or above using a novel data-driven method known as latent tree
analysis (LTA). METHOD: A cross-sectional survey on VMCI was carried out in
several regions in Northern China between February 2008 and February 2012 which
resulted in a data set that involves 803 patients and 93 symptoms. LTA was
performed on the data to reveal symptom co-occurrence patterns, and the patients
were partitioned into clusters in multiple ways based on the patterns. The
patient clusters were matched up with syndrome types, and population statistics
of the clusters are used to quantify the syndrome types and to establish
classification rules. RESULTS: Eight syndrome types are identified: Qi
deficiency, Qi stagnation, Blood deficiency, Blood stasis, Phlegm-dampness, Fire
heat, Yang deficiency, and Yin deficiency. The prevalence and symptom occurrence
characteristics of each syndrome type are determined. Quantitative classification
rules are established for determining whether a patient belongs to each of the
syndrome types. CONCLUSION: A solution for the TCM syndrome classification
problem for patients with VMCI and aged 50 or above is established based on the
LTA of unlabeled symptom survey data. The results can be used as a reference in
clinic practice to improve the quality of syndrome differentiation and to reduce
diagnosis variances across physicians. They can also be used for patient
selection in research projects aimed at finding biomarkers for the syndrome types
and in randomized control trials aimed at determining the efficacy of TCM
treatments of VMCI.
PMID- 28494850
TI - Efficacy of a traditional Persian medicine preparation for radiation-induced
xerostomia: a randomized, open-label, active-controlled trial.
AB - BACKGROUND: Xerostomia is one of the most common side effects of radiation
therapy among patients with head and neck cancers (HNC). However, conventional
medicine lacks an effective treatment for radiation-induced xerostomia.
OBJECTIVE: Synthesizing the traditional use of Alcea digitata and Malva
sylvestris with their known beneficial effects from recent studies, we evaluated
the efficacy of the herbs in the quality of life (QOL) of HNC patients with
radiation-induced xerostomia. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS:
This study is a randomized, double-arm, open-label active-controlled clinical
trial. We evaluated the effect of A. digitata and M. sylvestris on QOL of HNC
patients with radiation-induced xerostomia compared with Hypozalix (artificial
saliva). Patients were enrolled from the Imam Hossein Hospital's oncology clinic
in Shahid Beheshti University of Medical Sciences, Tehran, Iran. MAIN OUTCOME
MEASURES: Primary outcome measures in this trial were changes in patients' QOL
assessed by the European Organization for Research and Treatment of Cancer
Quality of Life Questionnaire, Head and Neck Module (EORTC QLQ-H&N 35). RESULTS:
Between-group analysis showed that the intervention group patients obtained
significantly lower (better) total EORTC QLQ-H&N 35 scores as compared to the
control group at the end of the intervention period (P = 0.007). Mean scores of
dry mouth of EORTC QLQ-H&N 35 was also significantly lower (better) in the
intervention group as compared to the control group (P = 0.017). CONCLUSION:
Traditional Persian medicine preparation of hollyhocks and common mallow should
be considered as a suitable treatment for xerostomia and improving QOL in HNC
patients with radiation-induced xerostomia. TRIAL REGISTRATION: The trial was
registered in ClinicalTrials.gov with Identifier: NCT02854358.
PMID- 28494851
TI - Effects of homoeopathic ultrahigh dilutions of Aconitum napellus on Baker's yeast
induced fever in rabbits.
AB - OBJECTIVE: To evaluate the effects of homoeopathic ultrahigh dilutions of
Aconitum napellus in Baker's yeast-induced fever in rabbits. METHODS: Rabbits
were divided into 4 groups and each group contained 6 rabbits. Baker's yeast
suspension (20%) was injected subcutaneously. After fever induction, paracetamol
and homoeopathic ultrahigh dilutions (A. napellus 200c and 1 000c) were given
orally. Rectal temperature was measured with digital thermometer hourly. RESULTS:
Fever was induced in all the rabbits after 4 hours of Baker's yeast
administration. A. napellus 200c and 1000c significantly reduced the temperature
(P < 0.05). In positive control, temperature decrease was more significant (P <
0.001). CONCLUSION: The above findings indicate the effectiveness of ultrahigh
dilutions of A. napellus in Baker's yeast-induced fever in rabbits. However, the
effects were slower and less significant than standard medicine. Moreover, future
research is required to know their mechanism of reducing temperature.
PMID- 28494852
TI - Atomic force microscopy correlates antimetastatic potentials of HepG2 cell line
with its redox/energy status: effects of curcumin and Khaya senegalensis.
AB - OBJECTIVE: The fatality of cancer is mostly dependent on the possibility of
occurrence of metastasis. Thus, if the development of metastasis can be prevented
through novel therapeutic strategies targeted against this process, then the
success of cancer treatment will drastically increase. In this study, therefore,
we evaluated the antimetastatic potentials of an extract of Khaya senegalensis
and curcumin on the metastatic liver cell line HepG2, and also assessed the
anticancer property of the extract. METHODS: Cells were cultured and treated with
graded concentrations of test substances for 24, 48, or 72 h with provisions made
for negative controls. Treated cells were assessed as follows:
nanotechnologically - atomic force microscopy (AFM) was used to determine cell
stiffness; biochemically - cell cytotoxicity, glutathione level and adenosine
triphosphate status, caspase activation and mitochondrial toxicity were
considered; and microbiologically - a carrot disk assay was used to assess the
anticancer property of the extract of K. senegalensis. RESULTS: Curcumin and K.
senegalensis increased the cell stiffness by 2.6- and 4.0-fold respectively,
indicating their antimetastatic effects. Corresponding changes in redox
(glutathione level) and energy (adenosine triphosphate) status of the cells were
also demonstrated. Further mechanistic studies indicated that curcumin was not
mitotoxic in HepG2 cells unlike the K. senegalensis extract. In addition, the
extract potently inhibited the Agrobacterium tumefaciens-induced genetic
transformation based on carrot disk assay. CONCLUSION: Cell elasticity
measurement data, using AFM, strongly suggested, for the first time, that both
curcumin and the extract of K. senegalensis exhibited antimetastatic properties
on HepG2 cells.
PMID- 28494853
TI - In vitro antioxidant assessment and a rapid HPTLC bioautographic method for the
detection of anticholinesterase inhibitory activity of Geophila repens.
AB - OBJECTIVE: Geophila repens (L.) I. M. Johnst. (Rubiaceae), a small, creeping,
perennial herb, is claimed to have memory-enhancing property. The goal of this
study was to assess its antioxidant and anticholinesterase activity and conduct a
rapid bioautographic enzyme assay for screening acetylcholinesterase (AChE) and
butyrylcholinesterase (BChE) inhibition of G. repens extracts. METHODS:
Antioxidant activity of G. repens extracts was assessed by performing 1,1
diphenyl-2-picrylhydrazyl (DPPH), nitric oxide (NO), superoxide (SOD), hydroxyl
(OH) and total antioxidant capacity (TAC) assays. Anticholinesterase activity was
investigated by quantifying the AChE and BChE inhibitory activities of chloroform
(CGR), ethyl acetate (EGR) and methanol (MGR) extract fractions from G. repens
leaves. A rapid high-performance thin-layer chromatography (HPTLC) bioautographic
method for the detection of AChE and BChE inhibition was performed. RESULTS:
Among all extract fractions, EGR exhibited the highest half maximal inhibitory
concentration (IC50) in DPPH, SOD, NO, OH and TAC assays, with IC50 of (38.33 +/-
3.21), (45.14 +/- 1.78), (59.81 +/- 1.32), (39.45 +/- 0.79) and (43.76 +/- 0.81)
MUg/mL respectively. EGR displayed competitive, reversible inhibition of AChE and
BChE activities with IC50 of (68.63 +/- 0.45) and (59.45 +/- 0.45) MUg/mL,
respectively. Total phenolic and flavonoids contents of EGR were found to be
360.42 mg gallic acid equivalents and 257.31 mg quercetin equivalents per gram of
extract. Phytoconstituents of the EGR extract that were inhibitors of
cholinesterase produced white spots on the yellow background of HPTLC plates in
the bioautographic test. CONCLUSION: The results of this study revealed that
phenols and flavonoids could be responsible for the antioxidant,
anticholinesterase activities of G. repens.
PMID- 28494854
TI - Yangfei Kongliu Formula, a compound Chinese herbal medicine, combined with
cisplatin, inhibits growth of lung cancer cells through transforming growth
factor-beta1 signaling pathway.
AB - OBJECTIVE: To investigate the tumor inhibition effect of Yangfei Kongliu Formula
(YKF), a compound Chinese herbal medicine, combined with cisplatin (DDP) and its
action mechanisms. METHODS: C57BL/6 mice with Lewis lung carcinoma were divided
into six groups: control group (C), DDP group (2 mg/kg, DDP), low-dose YKF group
(2.43 g/kg, L), high-dose YKF group (24.3 g/kg, H), low-dose YKF combined with
DDP group (L + DDP) and high-dose YKF combined with DDP group (H + DDP).
Transforming growth factor-beta1 (TGF-beta1), mothers against decapentaplegic
homolog 3 (Smad3) and Smad7 levels were measured with quantitative real-time
polymerase chain reaction (qPCR), Western blotting and immunohistochemistry. An
enzyme-linked immunosorbent assay was used to analyze the expressions of
interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha). RESULTS: YKF
combined with DDP significantly inhibited the growth and metastasis of tumors
relative to the control group, and YKF groups (P < 0.05). There was no
significant difference between high-dose YKF group and low-dose YKF group (P >
0.05). We also found that the expression levels of TGF-beta1 and Smad3 were both
significantly decreased by YKF relative to the control group (P < 0.05).
Furthermore, after treatment with YKF combined with DDP, the expression levels of
TGF-beta1 and Smad3 were decreased but the expression level of Smad7 was
increased relative to the DDP group (P < 0.05). Compared to the DDP group, the
combination of YKF and DDP enhanced the effect of tumor inhibition (P < 0.05),
showing obvious synergy between YKF and DDP. Treatment with DDP or YKF decreased
serum levels of IL-2 and TNF-alpha relative to the control group (P < 0.05).
Furthermore, the expression levels of IL-2 and TNF-alpha were significantly
decreased when treated with YKF in combination with DDP. Co-treatment with YKF
and DDP significantly inhibited tumor growth, decreased the expressions of TGF
beta1, Smad3, IL-2 and TNF-alpha and increased the expression of Smad7; these
differences were significant relative to both YKF groups and the control group (P
< 0.05). CONCLUSION: YKF can inhibit tumor growth synergistically with DDP,
mainly through the TGF-beta1 signaling pathway.
PMID- 28494855
TI - A complication of wet cupping therapy: vesiculobullous plaque on an erythematous
base.
PMID- 28494856
TI - Addressing the ethical issues raised by synthetic human entities with embryo-like
features.
AB - The "14-day rule" for embryo research stipulates that experiments with intact
human embryos must not allow them to develop beyond 14 days or the appearance of
the primitive streak. However, recent experiments showing that suitably cultured
human pluripotent stem cells can self-organize and recapitulate embryonic
features have highlighted difficulties with the 14-day rule and led to calls for
its reassessment. Here we argue that these and related experiments raise more
foundational issues that cannot be fixed by adjusting the 14-day rule, because
the framework underlying the rule cannot adequately describe the ways by which
synthetic human entities with embryo-like features (SHEEFs) might develop morally
concerning features through altered forms of development. We propose that limits
on research with SHEEFs be based as directly as possible on the generation of
such features, and recommend that the research and bioethics communities lead a
wide-ranging inquiry aimed at mapping out solutions to the ethical problems
raised by them.
PMID- 28494857
TI - Correction: Addressing the ethical issues raised by synthetic human entities with
embryo-like features.
PMID- 28494858
TI - mTORC1 Balances Cellular Amino Acid Supply with Demand for Protein Synthesis
through Post-transcriptional Control of ATF4.
AB - The mammalian target of rapamycin complex 1 (mTORC1) is a master regulator of
cell growth that is commonly deregulated in human diseases. Here we find that
mTORC1 controls a transcriptional program encoding amino acid transporters and
metabolic enzymes through a mechanism also used to regulate protein synthesis.
Bioinformatic analysis of mTORC1-responsive mRNAs identified a promoter element
recognized by activating transcription factor 4 (ATF4), a key effector of the
integrated stress response. ATF4 translation is normally induced by the
phosphorylation of eukaryotic initiation factor 2 alpha (eIF2alpha) through a
mechanism that requires upstream open reading frames (uORFs) in the ATF4 5' UTR.
mTORC1 also controls ATF4 translation through uORFs, but independently of changes
in eIF2alpha phosphorylation. mTORC1 instead employs the 4E-binding protein (4E
BP) family of translation repressors. These results link mTORC1-regulated demand
for protein synthesis with an ATF4-regulated transcriptional program that
controls the supply of amino acids to the translation machinery.
PMID- 28494860
TI - Overexpression of Trophoblast Stem Cell-Enriched MicroRNAs Promotes Trophoblast
Fate in Embryonic Stem Cells.
AB - The first cell fate choice of the preimplantation embryo generates the
extraembryonic trophoblast and embryonic epiblast lineages. Embryonic stem cells
(ESCs) and trophoblast stem cells (TSCs) can be utilized to investigate molecular
mechanisms of this first cell fate decision. It has been established that ESCs
can be induced to acquire trophoblast lineage characteristics upon manipulation
of lineage-determining transcription factors. Here, we have interrogated the
potential of microRNAs (miRNAs) to drive trans-differentiation of ESCs into the
trophoblast lineage. Analysis of gene expression data identified a network of TSC
enriched miRNAs that were predicted to target mRNAs enriched in ESCs. Ectopic
expression of these miRNAs in ESCs resulted in a stable trophoblast phenotype,
supported by gene expression changes and in vivo contribution potential. This
process is highly miRNA-specific and dependent on Hdac2 inhibition. Our
experimental evidence suggests that these miRNAs promote a mural trophectoderm
(TE)-like cell fate with physiological properties that differentiate them from
the polar TE.
PMID- 28494859
TI - HIV Reprograms Human Airway Basal Stem/Progenitor Cells to Acquire a Tissue
Destructive Phenotype.
AB - While highly active anti-retroviral therapy has dramatically improved the
survival of HIV-infected individuals, there is an increased risk for other co
morbidities, such as COPD, manifesting as emphysema. Given that emphysema
originates around the airways and that human airway basal cells (BCs) are adult
airway stem/progenitor cells, we hypothesized that HIV reprograms BCs to a
distinct phenotype that contributes to the development of emphysema. Our data
indicate that HIV binds to but does not replicate in BCs. HIV binding to BCs
induces them to acquire an invasive phenotype, mediated by upregulation of MMP-9
expression through activation of MAPK signaling pathways. This HIV-induced
"destructive" phenotype may contribute to degradation of extracellular matrix and
tissue damage relevant to the development of emphysema commonly seen in HIV+
individuals.
PMID- 28494861
TI - Excitatory Microcircuits within Superficial Layers of the Medial Entorhinal
Cortex.
AB - The distinctive firing pattern of grid cells in the medial entorhinal cortex
(MEC) supports its role in the representation of space. It is widely believed
that the hexagonal firing field of grid cells emerges from neural dynamics that
depend on the local microcircuitry. However, local networks within the MEC are
still not sufficiently characterized. Here, applying up to eight simultaneous
whole-cell recordings in acute brain slices, we demonstrate the existence of
unitary excitatory connections between principal neurons in the superficial
layers of the MEC. In particular, we find prevalent feed-forward excitation from
pyramidal neurons in layer III and layer II onto stellate cells in layer II,
which might contribute to the generation or the inheritance of grid cell
patterns.
PMID- 28494862
TI - Asynchronous Cholinergic Drive Correlates with Excitation-Inhibition Imbalance
via a Neuronal Ca2+ Sensor Protein.
AB - Excitation-inhibition imbalance in neural networks is widely linked to
neurological and neuropsychiatric disorders. However, how genetic factors alter
neuronal activity, leading to excitation-inhibition imbalance, remains unclear.
Here, using the C. elegans locomotor circuit, we examine how altering neuronal
activity for varying time periods affects synaptic release pattern and animal
behavior. We show that while short-duration activation of excitatory cholinergic
neurons elicits a reversible enhancement of presynaptic strength, persistent
activation results to asynchronous and reduced cholinergic drive, inducing
imbalance between endogenous excitation and inhibition. We find that the neuronal
calcium sensor protein NCS-2 is required for asynchronous cholinergic release in
an activity-dependent manner and dampens excitability of inhibitory neurons non
cell autonomously. The function of NCS-2 requires its Ca2+ binding and membrane
association domains. These results reveal a synaptic mechanism implicating
asynchronous release in regulation of excitation-inhibition balance.
PMID- 28494864
TI - Distinct Translaminar Glutamatergic Circuits to GABAergic Interneurons in the
Neonatal Auditory Cortex.
AB - GABAergic activity is important in neocortical development and plasticity.
Because the maturation of GABAergic interneurons is regulated by neural activity,
the source of excitatory inputs to GABAergic interneurons plays a key role in
development. We show, by laser-scanning photostimulation, that layer 4 and layer
5 GABAergic interneurons in the auditory cortex in neonatal mice (300 previously unpublished samples, we
identify cancer cell and tumor archetypes and suggest the tumor microenvironment
as a major prognostic determinant that can be influenced by the microbiome.
Notably, our subtyping strategy allowed identification of archetype-specific
prognostic biomarkers that provided information beyond and independent of UICC
TNM staging, MSI status, and consensus molecular subtyping. The results
illustrate that our extended subtyping framework, combining subtyping and subtype
specific biomarkers, could contribute to improved patient prognostication and may
form a strong basis for future studies.
PMID- 28494876
TI - Comparing performance of Fastrach ILMA vs flexible bronchoscope for awake
intubation.
PMID- 28494877
TI - Prevalence of malignant hyperthermia diagnosis in hospital discharge records in
California, Florida, New York, and Wisconsin.
AB - STUDY OBJECTIVE: Malignant hyperthermia (MH) is a rare yet potentially fatal
pharmacogenetic disorder triggered by exposure to inhalational anesthetics and
the depolarizing neuromuscular blocking agent succinylcholine. Epidemiologic data
on the geographic variation in MH prevalence is scant. The objective of this
study is to examine the prevalence of recorded MH diagnosis in patients
discharged from hospitals in four states in the United States. DESIGN:
Observational study. SETTING: Healthcare Cost and Utilization Project (HCUP)
State Inpatient Database (SID) for California (2011), Florida (2011), New York
(2012) and Wisconsin (2012). PATIENTS: A total of 164 hospital discharges that
had a recorded diagnosis of MH using the International Classification of Disease,
9th Revision, Clinical Modification code 995.86. METHODS: MH prevalence was
assessed by patient demographic and clinical characteristics. MAIN RESULTS: The
prevalence of MH per 100,000 hospital discharges ranged from 1.23 (95% Confidence
Interval [CI], 0.80-1.66) in New York to 1.91 (95% CI, 1.48-2.34) in California,
and the prevalence of MH per 100,000 surgical discharges ranged from 1.47 (95%
CI, 0.93-2.02) in New York to 2.86 (95% CI, 2.00-3.71) in Florida. The prevalence
of MH in male patients was more than twice the prevalence in female patients. Of
the 164 patients with MH diagnosis, 11% were dead on discharge. CONCLUSIONS:
There exists a modest variation in the prevalence of recorded MH diagnosis in
hospital discharges in California, Florida, New York and Wisconsin. Epidemiologic
patterns of MH diagnosis in hospital discharges appear to be similar across the
four states. Further research is needed to better understand the geographic
variation and contributing factors of MH in different populations.
PMID- 28494879
TI - Could Brugada Syndrome complicate anesthesia?
PMID- 28494878
TI - Factors influencing postoperative pain following discharge in pediatric
ambulatory surgery patients.
AB - STUDY OBJECTIVE: To identify demographic, intraoperative, and parental factors
that influence the postoperative pain experience in ambulatory surgery pediatric
patients. We also monitored postoperative maladaptive behavior changes (PMBCs) to
investigate the relationship between pain and PMBCs. DESIGN: Prospective cohort
study. SETTING: Discharge period after ambulatory surgery. PATIENTS: 204 patients
ages 1-6years undergoing ambulatory orthopedic, urology, general surgery, and
otolaryngology surgical procedures who were American Society of Anesthesiologists
(ASA) physical status I or II. INTERVENTIONS: None. MEASUREMENTS: We administered
telephone questionnaires to parents of ambulatory surgery patients 1-6years old
exploring pain ratings, behavior change ratings, and medication compliance at 2
3days and 1-2weeks after surgery. Pain and behavioral change scores were obtained
using the Parents Postoperative Pain Measure (PPPM) and Post-Hospital Behavior
Questionnaire (PHBQ). Parental medication compliance was defined as parents who
followed the discharge instructions for pain medication administration. MAIN
RESULTS: For our cohort, 69% of patients experienced pain after 2-3days and 17%
after 1-2weeks post-discharge. PMBCs were reported in 55% after 2-3days, and in
15% after 1-2weeks. In addition, PMBCs occurred in the absence of pain (PPPM=0)
at rates of 20% and 5% at 2-3days and 1-2weeks after surgery, respectively.
Female sex, anesthesia duration, and otolaryngology procedures correlated with
higher postoperative pain (PPPM) scores in univariate and multivariate analysis.
Intraoperative medications did not correlate with PPPM or PHBQ scores. Higher
pain scores were associated with parents who were compliant with discharge
instructions for pain medications. CONCLUSIONS: Many pediatric patients
experienced short-term pain and PMBCs after ambulatory surgery, but these largely
resolved by 1-2weeks following discharge. Patient sex, anesthesia duration, and
surgical procedure influenced postoperative pain and/or PMBCs. Furthermore, PMBCs
were associated with, but not solely a manifestation of, postoperative pain.
PMID- 28494880
TI - Noninvasive mechanical ventilation during spontaneous breathing anaesthesia: Can
electrical impedance tomography be a useful bedside tool to titrate PEEP level?
PMID- 28494881
TI - Effective nasal mask ventilation of a difficult airway in a patient with advanced
salivary gland cancer.
PMID- 28494882
TI - Use of the Laryngeal Mask Airway (LMA) ProtectorTM for shoulder surgeries in
beach-chair position.
PMID- 28494883
TI - Optimal timing for telescoping endotracheal tube into an introducer during
nasotracheal intubation.
PMID- 28494884
TI - Less postoperative sore throat after nasotracheal intubation using a fiberoptic
bronchoscope than using a Macintosh laryngoscope: A double-blind, randomized,
controlled study.
AB - STUDY OBJECTIVE: To evaluate whether nasotracheal intubation using a fiberoptic
bronchoscope reduces postoperative sore throat. DESIGN: Prospective, double
blinded, randomized, and controlled study. SETTING: Postoperative areas and
surgical ward of a university hospital. PATIENTS: Seventy-four patients with
American Society of Anesthesiologists physical status I-II who were scheduled for
elective general anesthesia requiring nasotracheal intubation. INTERVENTIONS:
Patients were randomized to one of two intubation groups, F (fiberoptic
bronchoscope-guided) and M (Macintosh laryngoscope-guided), and after induction
of general anesthesia, the patients' tracheas were intubated via the nose.
MEASUREMENTS: The intensity of postoperative sore throat was evaluated using a
numerical rating score (0=none, 10=severe) at 24 hours postoperatively, and the
incidence of nasal mucosal trauma, time to completion of intubation, and
hemodynamic responses were recorded and compared between groups. MAIN RESULTS:
The numerical rating score value was significantly lower in group F than in group
M (P=.0047), but the incidence of nasal mucosal trauma was comparable between the
two groups. The median time to completion of intubation was shorter for group F
than group M (P<.0001). Hemodynamic responses were not significantly different.
CONCLUSIONS: Fiberoptic bronchoscope-guided intubation is associated with less
sore throat after nasotracheal intubation than M intubation. The time to
completion of intubation was significantly shorter using the fiberoptic
bronchoscope than that using the Macintosh laryngoscope.
PMID- 28494885
TI - Importance of relying on examples for both anesthesiologists and other physicians
to assign unbiased American Society of Anesthesiologists Physical Status
Classifications.
PMID- 28494886
TI - Determining predictive value of preoperative tests for difficult intubation.
PMID- 28494887
TI - Preoperative risk stratification of critically ill patients.
AB - STUDY OBJECTIVE: Risk assessment historically emphasized cardiac morbidity and
mortality in elective, outpatient, non-cardiac surgery. However, critically ill
patients increasingly present for therapeutic interventions. Our study
investigated the relationship of American Society of Anesthesiologists (ASA)
class, revised cardiac risk index (RCRI), and sequential organ failure assessment
(SOFA) score with survival to discharge in critically ill patients with
respiratory failure. DESIGN: Retrospective cohort analysis over a 21-month
period. SETTING: Five adult intensive care units (ICUs) at a single tertiary
medical center. PATIENTS: Three hundred fifty ICU patients in respiratory
failure, who underwent 501 procedures with general anesthesia. MEASUREMENTS:
Demographic, clinical, and surgical variables were collected from the pre
anesthesia evaluation forms and preoperative ICU charts. The primary outcome was
survival to discharge. MAIN RESULTS: Ninety-six patients (27%) did not survive to
discharge. There were significant differences between survivors and non-survivors
for ASA (3.7 vs. 3.9, p=0.001), RCRI (1.6 vs. 2.0, p=0.003), and SOFA score (8.1
vs. 11.2, p<0.001). Based on the area under the receiver operating characteristic
curve for these relationships, there was only modest discrimination between the
groups, ranging from the most useful SOFA (0.68) to less useful RCRI (0.60) and
ASA (0.59). CONCLUSIONS: This single center retrospective study quantified a high
perioperative risk for critically ill patients with advanced airways: one in four
did not survive to discharge. Preoperative ASA score, RCRI, and SOFA score only
partially delineated survivors and non-survivors. Given the existing limitations,
future research may identify assessment tools more relevant to discriminating
survival outcomes for critically ill patients in the perioperative environment.
PMID- 28494888
TI - Cerebral infarction in cervical plexus block.
PMID- 28494889
TI - Influence of the perioperative administration of magnesium sulfate on the total
dose of anesthetics during general anesthesia. A systematic review and meta
analysis.
AB - BACKGROUND: Magnesium sulfate displays numerous characteristics that make it a
useful drug in anesthesiology (N-methyl-d-aspartate receptor antagonist,
vasodilator, antiarrhythmic, inhibitor of catecholamine release and of
acetylcholine in the terminal motor plate). The perioperative use of this drug as
an adjuvant capable of decreasing the required dose of anesthetics, has been
proposed. OBJECTIVES: To assess the influence of intravenous magnesium sulfate
administration during general anesthesia on the overall dose of required
anesthetics. DESIGN: A systematic review of controlled randomized trials and meta
analysis. DATA SOURCES: An electronic bibliography search in MEDLINE and in the
Cochrane Database of Controlled trials (CENTRAL) up to 2015. STUDY ELIGIBILITY
CRITERIA, PARTICIPANTS AND INTERVENTIONS: Randomized, double-blind trials
relating to general anesthesia in elective surgery using intravenous magnesium
sulfate that provide information about the anesthetic requirements in ASA I and
II patients. RESULTS: 20 clinical trials were selected for the qualitative
analysis and 19 for the quantitative one. The use of perioperative intravenous
magnesium sulfate reduces the requirement of the anesthetic, propofol during
induction (-28.52mg; CI 95% -35.22-1.82; p<0.001) and maintenance (-213.56mg; CI
95% -322.93, -104.18; p<0.001) of anesthesia. Additionally, magnesium sulfate
reduces the requirement of neuromuscular non-despolarizing blocking agents (
2.99mg; CI 95% -44.47, -1.99; p<0.001) and the intraoperative consumption of
fentanile(-53.57 mcg; CI 95% -75.01, -32.12; p<0.001). CONCLUSIONS: We conclude
that perioperative magnesium sulfate acts as a coadjuvant drug capable of
reducing anesthetic requirements.
PMID- 28494890
TI - The predictive value of pre-recruitment achievement on resident performance in
anesthesiology.
AB - STUDY OBJECTIVE: Selecting candidates for residency positions is challenging and
there is little research on the correlation between commonly used selection
criteria and subsequent performance in anesthesiology. This study examined the
association between the selection measures and post-recruitment performance in
residency. DESIGN: Retrospective review of archival data. SETTING: Anesthesiology
residency program at a large academic anesthesiology department. SUBJECTS:
Residents who were matched to the anesthesiology program over 9years (graduation
classes of 2006 to 2014). INTERVENTIONS: None. MEASUREMENTS: The pre-recruitment
achievements included a comprehensive list of measures obtained from residents'
application portfolios in conjunction with interview performance. The post
recruitment examination outcomes consisted of the in-training examination (ITE)
scores in the three clinical anesthesia (CA) years and first-attempt success on
the written board certification examination administered by the American Board of
Anesthesiology (ABA). Scholarly output during residency was measured by
publication record. Clinical performance at the conclusion of residency was
independently rated by three faculty members. Bivariate analysis and regression
models were conducted to examine association between predictors and outcomes.
MAIN RESULTS: High United States Medical Licensing Examination (USMLE) scores,
class rank in medical school and interview performance were predictive of high
examination scores in residency and good clinical performance. Class rank
appeared to be the best predictor of scholarly publication and pursuing an
academic career beyond residency. CONCLUSIONS: Comparative performance with
classmates (i.e., class rank) in medical school appeared to be an effective
predictor of overall performance in residency, which warrants more attention in
future study. Although interview performance is subject to recruitment team
members' interpretation, it is an important measure to include in recruitment
decisions.
PMID- 28494891
TI - Clinical experiences of ultrasound-guided lateral thoracolumbar Interfascial
plane (TLIP) block.
PMID- 28494892
TI - Postoperative analgesic efficacy of single-shot and continuous transversus
abdominis plane block after laparoscopic cholecystectomy: A randomized controlled
clinical trial.
AB - STUDY OBJECTIVE: To compare the analgesic efficacy of ultrasound-guided single
shot and continuous transversus abdominis plane (TAP) block to that of IV-PCA in
patients undergoing laparoscopic cholecystectomy. DESIGN: Prospective randomized
controlled trial. SETTING: Post-anesthesia care unit and General ward. PATIENTS:
108 American Society of Anesthesiologist (ASA) physical status I-II patients
undergoing laparoscopic cholecystectomy. INTERVENTIONS: Group A received IV-PCA;
group B received both ultrasound-guided single-shot TAP block with 0.2%
ropivacaine (20mL) and IV-PCA; and group C received continuous TAP block using an
ultrasound-guidance-inserted indwelling catheter. In group C, infusion of 0.2%
ropivacaine at a basal rate of 3mL/h, bolus dose of 4mL, and a lockout interval
of 30min was maintained for 48h postoperatively. The primary outcome was
evaluated analgesic efficacy using the numeric rating scale (NRS) for 48h
postoperatively. Other outcomes included the number of patients requiring
additional analgesics, patient satisfaction with postoperative pain control, and
incidence of postoperative adverse events. MAIN RESULTS: Compared to other
groups, group C had higher deep abdominal NRS at 1h postoperatively (P<0.05), and
lower incidence of postoperative urinary retention (P<0.05). There were no
significant intergroup differences in the number of patients requiring additional
analgesics, and patient satisfaction with postoperative pain control.
CONCLUSIONS: Compared to IV-PCA with or without single-shot TAP block, ultrasound
guided continuous TAP block provided similar analgesia in somatic pain and less
analgesia in visceral pain. Moreover, the latter resulted in a lower incidence of
postoperative urinary retention.
PMID- 28494893
TI - Successful tracheal intubation with the McGRATHTM MAC during chest compression in
a difficult airway patient.
PMID- 28494894
TI - Dexamethasone for nerve blocks: Design matters!
PMID- 28494895
TI - The efficacy of Labetalol versus Nitroglycerin for induction of controlled
hypotension during sinus endoscopic surgery. A prospective, double-blind and
randomized study.
AB - OBJECTIVE: To assess the efficacy of labetalol versus nitroglycerin for induction
of controlled hypotension during sinus endoscopic surgery. DESIGN: A prospective,
double-blind and randomized study. SETTING: Carried out in operating room in
university hospital. PATIENTS: 60 patients of both sexes, American Society of
Anesthesiologists (ASA) physical status I and II, age range from 20 to 60years;
scheduled for elective sinus endoscopic surgery under general anesthesia (GA).
INTERVENTIONS: Patients were divided into two groups (30 each). NTG group
received nitroglycerin infusion at a dose of 2-5MUg/kg/min, LAB group received
labetalol infusion at a dose of 0.5-2mg/min. MEASUREMENTS: Surgical condition was
assessed by surgeon using average category scale (ACS) of 0-5, a value of 2-3
being ideal. In both groups mean arterial blood pressure (MAP) was gradually
reduced till the ideal ACS for assessment of surgical condition, the target of
ACS was 2-3 or lower. RESULTS: Both studied drugs achieved desired hypotension
and improved visualization of surgical field by decreasing bleeding in the
surgical site, but ideal surgical conditions were created at mild hypotension
(MAP 70-75) in LAB group while same conditions were created at MAP of 65-69mmHg
in NTG group. Mean heart rate (HR) was significantly higher in NTG group as
compared to LAB group. Blood loss decreased significantly in LAB group.
CONCLUSION: Both labetalol and NTG are effective and safe drugs for induction of
controlled hypotension during sinus endoscopic surgery. While, labetalol was
better as it offered optimum operative condition with mild decrease in blood
pressure, decreased surgical bleeding and less tachycardia during the surgery.
PMID- 28494896
TI - Occupational stress of anesthesia: Effects on aging.
AB - BACKGROUND: Anesthesiology has been identified as a stressful specialty. Chronic
psychological stress may lead to biological aging and skin aging. STUDY
OBJECTIVE: The primary outcome was to measure physical health and emotional well
being. Secondary outcomes include skin aging analysis, telomere shortening in
anesthetists. DESIGN: This is a prospective observational study. SETTINGS:
University of Alexandria. PATIENTS: Study was carried out on 366 ASA I-II
physicians 30-50yr. INTERVENTIONS: Physicians were categorized into two equal
groups, Group A (183) were anesthesia physicians and Group B (183) were
physicians in less stressful specialties (laboratory specialties). Subgroup
analysis was performed comparing 10years' intervals from (30-40) and from (40
50). MEASUREMENTS: Physical health and emotional well-being were evaluated. All
physicians were exposed to validated assessment scales for the upper face and the
lower face for skin aging analysis. Blood sampling were drowned from all
physicians during their working hours for analysis of telomere length, markers of
oxidative stress. RESULTS: The two studied groups showed comparable demographic
data and years of work. Physical health score and emotional health score showed
higher values in Group A than Group B. Upper and lower face aesthetic unit
summary score showed higher values in Group A than Group B. Telomere (TTAGGG)
repeats for terminal restriction fragments (TRF) of Group A individuals revealed
a significant decrease of TRF compared to Group B (p=0.001*). CONCLUSION:
Biological and skin aging is evident in anesthetists who are chronically exposed
to occupational stress, with obvious shorter telomere length, higher lower and
upper face scores, and free radicals.
PMID- 28494897
TI - Successful one-lung ventilation using a bronchial blocker tube for a large
tracheal carcinoma resection.
PMID- 28494898
TI - The effect of desflurane versus propofol anesthesia on postoperative delirium in
elderly obese patients undergoing total knee replacement: A randomized,
controlled, double-blinded clinical trial.
AB - STUDY OBJECTIVE: The goal of this study was to investigate the incidence of
delirium, wake-up times and early post-operative cognitive decline in one hundred
obese elderly patients undergoing total knee arthroplasty. DESIGN: Prospective
randomized trial. SETTINGS: Operating room, postoperative recovery area, hospital
wards. PATIENTS: 100 obese patients (ASA II and III) undergoing primary total
knee replacement under general anesthesia with a femoral nerve block catheter.
INTERVENTION: Patients were prospectively randomized to maintenance anesthesia
with either propofol or desflurane. MEASUREMENTS: The primary endpoint assessed
by a blinded investigator was delirium as measured by the Confusion Assessment
Method. Secondary endpoints were wake-up times and a battery of six different
tests of cognitive function. MAIN RESULTS: Four of the 100 patients that gave
informed consent withdrew from the study. Of the remaining 96 patients, 6
patients did not complete full CAM testing. Preoperative pain scores, durations
of surgery and anesthesia, and amount of intraoperative fentanyl were not
different between groups. One patient in the propofol group developed delirium
compared to zero in desflurane. One patient in desflurane group developed a
confused state not characterized as delirium. Fifty percent of the patients
exhibited a 20% decrease in the results of at least one cognitive test on the
first 2days after surgery, with no difference between groups. There were no
differences in the time to emergence from anesthesia, incidence of postoperative
nausea and vomiting, and length of postanesthesia care unit (PACU) stay between
the two groups. CONCLUSIONS: In conclusion we found a low incidence of delirium
but significant cognitive decline in the first 48h after surgery. In this
relatively small sample size of a hundred patients there was no difference in the
incidence of postoperative delirium, early cognitive outcomes, or wake up times
between the desflurane or propofol group.
PMID- 28494899
TI - Perioperative management of patients with renal cell carcinoma with high level of
IVC tumor thrombus invasion revisited.
PMID- 28494900
TI - Perioperative strokes after coronary artery bypass grafting with staged carotid
endarterectomy: A nationwide perspective.
AB - STUDY OBJECTIVE: To examine the risk of perioperative stroke on in-hospital
morbidity and mortality in staged coronary artery bypass grafting (CABG) and
carotid endarterectomy (CEA) procedures. DESIGN: The National Inpatient Sample
(NIS) database was used to extract data on all patients who underwent staged CABG
CEA procedures. They were identified using the ICD-9 (International
Classification of Diseases, Ninth Revision-Clinical Modification) diagnosis and
procedure codes. SETTING: Multi-institutional. PATIENTS: Patients who underwent
staged CABG and CEA from 1999 to 2011. INTERVENTIONS: Staged CABG and CEA
procedures. MEASUREMENTS: Various pre-operative, and perioperative risk factors
and their association with in-hospital mortality and morbidity were studied. MAIN
RESULTS: The study cohort was grouped into 2761 patients who underwent staged CEA
and CABG. The average age of the patient population was 69years. An in-hospital
mortality of 4.96% (137) was observed. Staged procedures showed a morbidity rate
of 69.21%. Patients with perioperative strokes had a mortality rate of 16.73%
following staged procedures. Other notable risk factors for mortality and
morbidity were post-operative myocardial infarction (MI) and congestive heart
failure (CHF). CONCLUSION: Analysis of 2761 patients over a period of 12years
(1999-2011) indicate perioperative stroke to be a strong post-operative
predicator of in-hospital mortality and morbidity for staged procedures. Other
significant factors such as advancing age, female gender and comorbidities like
CHF, left ventricular dysfunction (LVD) and post-operative MI should also be
considered when determining patient risk. Further investigative studies on staged
CABG and CEA procedures are needed for better patient selection and for
implementing preventative strategies such as neuroprotective medication and
neuromonitoring to minimize the risk of ischemic strokes.
PMID- 28494901
TI - A novel skin traction method to facilitate ultrasound-guided femoral nerve block
in morbidly obese patients.
PMID- 28494902
TI - Intraoperative anxiety and acute glaucoma: A possible link?
PMID- 28494903
TI - Mom....Stop stressing me out!! Parental presence and its effect on cortisol
levels in children.
PMID- 28494904
TI - Complex regional pain syndrome type 1 predictors - Epidemiological perspective
from a national database analysis.
AB - OBJECTIVE: Complex regional pain syndrome type 1 is a disabling pain disorder
with unclear etiology. It is usually triggered by an injury to a limb with or
without specific nerve injury. The objective of this study is to explore the risk
factors and predictors for this disease utilizing a large national database.
DESIGN: Retrospective analysis of the Nationwide Inpatient Sample database from
2007 to 2011 in the United States. SETTING AND PATIENTS: Adult inpatients
diagnosed with complex regional pain syndrome type 1. STATISTICAL ANALYSIS: Chi
square, simple and multivariate logistic regression analyses were conducted. The
regression model was adjusted to the patient's demographics and comorbidities.
MAIN RESULTS: There were 22,533 patients with the discharge diagnosis of complex
regional pain syndrome type 1 of an inpatient sample of 33,406,123. It peaks
between age 45 and 55. Female gender, Caucasian race, higher median household
income, headache, depression, drug abuse and private insurance patients (vs
Medicaid patients) were associated with higher rate of complex regional pain
syndrome type 1. On the other hand, diabetes, obesity, hypothyroidism, and anemia
were associated with a lower rate. CONCLUSIONS: Utilizing a large database, our
study added more information to the risk profile of the complex regional pain
syndrome type 1 in an inpatient population. Such information should be useful for
physician for early recognition, diagnosis of patients at risk.
PMID- 28494905
TI - Role of sugammadex in accelerating postoperative discharge: A meta-analysis.
AB - STUDY OBJECTIVE: Sugammadex has been introduced for reversal of neuromuscular
blockade (NMB) induced by rocuronium (or vecuronium). Although its efficacy and
safety have been established, data are conflicting as to whether it accelerates
discharge to the surgical ward compared with neostigmine, which is traditionally
used for reversing NMB. The object of this systematic review and meta-analysis
was to review the research comparing sugammadex and neostigmine in the context of
patient discharge after general anesthesia. DESIGN: Systematic review and meta
analysis. SETTING: University medical hospital. PATIENTS: Five-hundred eighteen
patients from six studies were included. METHODS: A comprehensive search was
conducted using PubMed, Web of Science, Google Scholar, and Cochrane Library
electronic databases to identify randomized controlled trials written in English.
Two reviewers independently selected the studies, extracted data regarding
postoperative discharge, and assessed the trials' methodological quality and
evidence level. Postoperative discharge time was determined from the operating
room (OR) to the postanesthesia care unit (PACU) and from the PACU to the
surgical ward. This study was conducted using PRISMA methodology. MEASUREMENTS:
Time to discharge after NMB reversal with sugammadex or neostigmine. MAIN
RESULTS: Compared with neostigmine, sugammadex was associated with a
significantly faster discharge from the OR to the PACU (mean difference
[MD]=22.14min, 95% CI (14.62, 29.67), P<0.0001, I2=0%) and from the PACU to the
surgical ward (MD=16.95min, 95% CI (0.23, 33.67), P=0.0469, I2=98.4%). Similarly,
discharge-readiness was shorter for sugammadex than for neostigmine from the OR
to the PACU (MD=5.58min, 95% CI (3.03, 8.14), P<=0.0001, I2=0%). However,
discharge-readiness was similar in both groups for patients moving from the PACU
to the surgical ward (MD=-1.10min, 95% CI (-5.69, 3.50), P=0.6394, I2=25.3%).
CONCLUSIONS: Results from this meta-analysis suggest that sugammadex accelerates
postoperative discharge of patients after general anesthesia compared with
neostigmine.
PMID- 28494906
TI - The effect of morphine added to bupivacaine in ultrasound guided transversus
abdominis plane (TAP) block for postoperative analgesia following lower abdominal
cancer surgery, a randomized controlled study.
AB - OBJECTIVES: Transversus abdominis plane (TAP) block used for management of
surgical abdominal pain by injecting local anesthetics into the plane between the
internal oblique and transversus abdominis muscles. We aimed to explore the
effect of adding morphine to bupivacaine in ultrasound guided TAP-block in
patients undergoing lower abdominal cancer surgery. STUDY DESIGN: Randomized,
double-blind, prospective study. Clinical trial identifier: NCT02566096. SETTING:
Academic medical center. PATIENTS: Sixty patients were enrolled in this study
after ethical committee approval. INTERVENTIONS: Patients divided into 2 groups
(30 each): Bupivacaine group (GB): given ultrasound guided TAP-block 20ml 0.5%
bupivacaine diluted in 20ml saline; Morphine group (GM): given ultrasound guided
TAP-block with 20ml 0.5% bupivacaine+10mg morphine sulphate diluted in 20ml
saline. MEASUREMENTS: Patients were observed for total morphine consumption, time
for first request of rescue analgesia, sedation scores, hemodynamics and side
effects for 24h postoperatively. RESULTS: Morphine added to bupivacaine in TAP
block compared to bupivacaine alone reduced total morphine consumption (5.33+/
1.28mg) (10.70+/-3.09mg) respectively (p<0.001), prolonged the time to first
request of analgesia (10.40+/-4.96h) (6.97+/-3.26h) respectively (p<0.008), with
a statistically significant decrease in (VAS-M) in GM compared with GB at 12h
postoperatively (p<0.002). No significant differences in hemodynamics,
respiratory rate, oxygen saturation, sedation score, and side effects except for
nausea were observed (p>0.05). CONCLUSION: Addition of morphine to bupivacaine in
TAP block is effective method for pain management in patients undergoing major
abdominal cancer surgery without serious side effects.
PMID- 28494907
TI - Internet-delivered, preoperative, preparation program (I-PPP): Development and
examination of effectiveness.
AB - STUDY OBJECTIVE: Limited evidence-based, interactive, Internet-delivered
preoperative preparation programs for children and their parents exist. The
purpose of this investigation was to develop and examine the effectiveness of the
Internet-delivered, preoperative program (I-PPP) in alleviating prepoperative
anxiety in children undergoing outpatient surgery. In Study 1, the I-PPP was
developed and then evaluated by parent/child dyads and health care professionals.
In Study 2, the effectiveness of I-PPP was examined. DESIGN: This study was a
development and effectiveness study. SETTING: For Study 1, participants were
recruited from the community. For Study 2, participants were recruited from the
Royal University Hospital. PATIENTS: In Study 1, participants were 9 parent/child
dyads and 5 health care professionals. In Study 2, participants were 32 children
(3-7years) scheduled for outpatient surgery and one parent for each child.
INTERVENTION: In Study 1, I-PPP modules were created and parent/child dyads and
health care professionals evaluated I-PPP modules and treatment credibility. In
Study 2, child patients and their parents completed the I-PPP prior to day of
surgery. MEASUREMENTS: Observer-rated anxiety of child participants was measured
during the day surgery experience. Parent state anxiety was measured prior to
completing I-PPP, pre- and post-surgery. Post-surgery parents provided comments
regarding the I-PPP. Post-surgery child behaviour change was assessed. MAIN
RESULTS: For Study 1, ratings for I-PPP components and treatment credibility
surpassed our acceptability criterion. Minor changes were made to I-PPP. For
Study 2, mYPAS scores were stable across day surgery. mYPAS scores in current
study at induction did not differ significantly from benchmark studies.
Significant reduction in parent anxiety was observed pre- to post-surgery.
Parents positively endorsed the program. Negative post-operative behaviours were
observed in a proportion of children. CONCLUSIONS: Our findings suggest that I
PPP represents a viable option for preoperative preparation for children and
their parents.
PMID- 28494908
TI - For assessment of changes in intraoperative red blood cell transfusion practices
over time, the pooled incidence of transfusion correlates highly with total units
transfused.
AB - STUDY OBJECTIVE: Multiple studies nationwide and at single hospitals have
examined changes over time in the incidence of perioperative red blood cell (RBC)
transfusion. However, the cost of RBC transfusions is related to the number of
RBC units transfused, not to the incidence. We evaluate whether the readily
available incidence of RBC transfusion can be used as a valid surrogate measure.
DESIGN: Observational retrospective study. SETTING: One tertiary, academic
hospital. PATIENTS: 394,789 cases of 1885 procedures over N=42 quarters of the
year. INTERVENTIONS: None. MEASUREMENT: Incidence and number of RBC units
transfused intraoperatively. MAIN RESULTS: The number of RBC units transfused per
case did not follow a Poisson distribution, confirming that the number of units
and incidence of transfusion are not interchangeable for analyzing decisions by
case. However, with all cases of each quarter combined, the Spearman correlation
was 0.98+/-0.01 between each quarter's incidence of RBC transfusion and mean RBC
units transfused per case (P<0.0001). CONCLUSIONS: For assessment of changes in
intraoperative RBC transfusion practices over years, it is sufficient to analyze
the pooled incidence of transfusion, rather than to calculate the number of units
transfused.
PMID- 28494909
TI - Remifentanil as an alternative to epidural analgesia for vaginal delivery: A meta
analysis of randomized trials.
AB - OBJECTIVES: Although epidural analgesia is considered the gold standard for labor
pain management, its use may be restricted in some conditions due to clinical
contraindications or availability, and suitable alternatives may be required. The
objective of this meta-analysis was to determine whether evidence from randomized
trials suggests remifentanil PCA (R-PCA) results in significant differences in
maternal satisfaction, analgesic efficacy, and safety compared with conventional
epidural analgesia (EA). DESIGN: We conducted a meta-analysis after
systematically searching MEDLINE, EMBASE and Cochrane Library for all randomized
controlled trials (RCTs) allocating parturients to R-PCA or EA and reporting at
least one outcome of interest. PATIENTS: Eight randomized trials of R-PCA vs EA
with 2351 patients were included. MEASUREMENTS: The primary outcome of interest
was maternal satisfaction. Secondary outcomes included visual analog pain score
(VAS at 1, 2, 3h postoperatively), nausea, vomiting, pruritus, hypoxemia, acute
respiratory depression or death (maternal or neonatal), need for Cesarean
section, and neonatal Apgar score. MAIN RESULTS: Meta-analysis of the randomized
trials showed no significant differences between the R-PCA and EA groups for
maternal satisfaction, VAS at 2 or 3h, nausea, vomiting, need for cesarean
section, respiratory depression, umbilical pH, and neonatal Apgar score at 1min
and 5min. However, incidence of hypoxemia was higher [OR 7.48, 95%CI 3.42-16.36]
and VAS at 1h was slightly higher [WMD 1.33, 95%CI 0.30-2.36] with R-PCA versus
EA. Pruritus was less frequent in the R-PCA group [OR 0.54, 95%CI 0.32-0.89].
Acute respiratory failure and death were not reported in any of the studies.
CONCLUSIONS: While no significant differences were detected for maternal
satisfaction or for most clinical outcomes, this meta-analysis remains
underpowered to rule out clinically-important differences due to the few existing
randomized trials. For obstetric patients who are not candidates for EA, R-PCA
may provide an alternative for analgesia in the peri-partum period, but caution
is warranted particularly regarding hypoxemia, and suggests the need for
increased surveillance and monitoring for R-PCA. Further adequately powered
randomized trials with a focus on clinically-relevant maternal and neonatal
outcomes are required to more accurately characterize the relative benefits and
risks of R-PCA versus EA in this population.
PMID- 28494910
TI - The effects of maternal presence during anesthesia induction on salivary cortisol
levels in children undergoing tonsillectomy and/or adenoidectomy.
AB - OBJECTIVE: Although parental presence during anesthesia induction is suggested to
diminish operative stress level in children, there have been conflicting results
about this strategy. The aim of this study was to evaluate the effects of
maternal presence during induction on operative stress level in children who had
tonsillectomy and/or adenoidectomy by determining the salivary cortisol levels.
DESIGN: Non-randomized clinical study. SETTING: Preoperative and postoperative
recovery rooms, operating room. PATIENTS: The study included 48 children between
the ages of 5-12years who underwent tonsillectomy and/or adenoidectomy.
INTERVENTIONS: The patients were divided into 2 groups. The children in group 1
were separated from their mothers at the preparation room. The children in group
2 stayed together with their mothers till the anesthesia induction. MEASUREMENTS:
State Trait Anxiety Inventory (STAI) was performed to the mothers and children
preoperatively. Salivary cortisol levels were evaluated in 4 different time
frames: 1) in preparation room, 2) after anesthesia induction, 3) at the 30th
minute of operation, and 4) in postoperative recovery room. MAIN RESULTS: There
were no statistically significant differences between groups regarding
demographic features, and operation or anesthesia times. The child's or mothers'
preoperative anxiety scores were not different between the groups. Salivary
cortisol levels in group 1 were significantly increased after induction and in
recovery room compared to those in group 2 (p: 0.001, and p: 0.02, respectively).
CONCLUSIONS: We have determined decreased salivary cortisol levels during
anesthesia induction and recovery in the maternal presence revealing diminished
stress in these periods. Further studies are warranted to determine the effects
of parental presence during anesthesia induction especially on surgical outcomes.
PMID- 28494912
TI - ASA physical status classification system: Is it consistent amongst providers and
useful in determining need for pre-operative evaluation resources?
PMID- 28494911
TI - Levosimendan does not provide mortality benefit over dobutamine in adult patients
with septic shock: A meta-analysis of randomized controlled trials.
AB - OBJECTIVES: Despite of advancement in intensive care medicine, sepsis and septic
shock carry a high mortality. Levosimendan, an inodilator, may be promising for
septic shock patients with myocardial dysfunction; however, firm evidence is
lacking. In this meta- analysis of randomized controlled trials, levosimendan has
been compared with dobutamine in adult patients with sepsis and septic shock.
DESIGN: Meta-analysis of randomized controlled trial. SETTING: Intensive-care
unit. PARTICIPANTS: Adult septic shock patients. INTERVENTION: Adult septic shock
patients received dobutamine or levosimendan. MAIN OUTCOME MEASURE: Mortality at
longest follow-up, blood lactate level, cardiac index and noradrenaline
requirement. RESULTS: Data from 7 randomized trials have been included in this
meta-analysis. Levosimendan has no benefit in terms of mortality at longest
follow up in comparison to dobutamine (Odds ratio 0.77, 95% CI 0.45, 132; p=0.34)
and length of ICU stay (MD -4.7days, 95% CI -10.3, 0.9days, p=0.10). Patients
received levosimendan had less blood lactate level (standardized mean difference
0.95; 95% CI -1.64, -0.27; p=0.006) and higher cardiac index (mean difference
0.44; 95% CI 0.17, 0.71; p=0.001). Noradrenaline requirements are similar in both
the groups. CONCLUSION: There is no evidence that levosimendan is superior to
dobutamine in adult patients with sepsis and septic shock. Further large
randomized trials are necessary in this area.
PMID- 28494913
TI - Epidural catheter cutting: mechanisms and management.
PMID- 28494914
TI - The effect of melatonin on early postoperative cognitive decline in elderly
patients undergoing hip arthroplasty: A randomized controlled trial.
AB - STUDY OBJECTIVE: The purpose of the present study was to investigate whether
exogenous melatonin supplementation could ameliorate early postoperative
cognitive decline (POCD) in aged patients undergoing hip arthroplasty with spinal
anesthesia. DESIGN: Prospective cohort study. SETTING: Department of
Anesthesiology, Jinling Hospital, Nanjing University, Nanjing, China. PATIENTS:
One hundred and thirty-nine patients with ASA I-III, older than 65yr of age (mean
age: 74.5+/-5.5; gender: male 53 and female 86), scheduled for hip arthroplasty
were included in the present study. INTERVENTIONS: Patients were randomized to
receive 1mg oral melatonin or placebo daily 1h before bedtime one day before
surgery and for another 5 consecutive days postoperatively. MEASUREMENTS: The
subject assessment, including Mini-Mental State Examination (MMSE) score,
subjective sleep quality, general well-being, postoperative fatigue, and visual
analogue scale for pain were evaluated pre-operatively and at days 1, 3, 5, and 7
after surgery. MAIN RESULTS: The MMSE score in the control group decreased
significantly after surgery when compared with its own preoperative value or the
melatonin group at days 1, 3, and 5. However, the MMSE score in the melatonin
group remained unchanged during the 7days of monitoring. In addition, significant
postoperative impairments of subjective sleep quality, general well-being, and
fatigue were found in the control group when compared with the melatonin group.
CONCLUSION: Peroperative melatonin supplementation might improve early POCD,
suggesting restoration of normal circadian function with good sleep quality may
be one of the key factors in preventing or treating POCD.
PMID- 28494915
TI - Injection speed of spinal anaesthesia for Caesarean delivery in Asian women and
the incidence of hypotension: A randomised controlled trial.
AB - STUDY OBJECTIVE: The purpose of this investigation was to determine if a slower
speed of spinal anaesthesia injection would reduce the incidence of hypotension.
STUDY DESIGN: Randomised controlled trial. SETTING: Tertiary level hospital in
Malaysia. PATIENTS: 77 patients undergoing elective Caesarean delivery.
INTERVENTION: Differing speeds of spinal injection. MEASUREMENTS: Systolic blood
pressure was assessed every minute for the first 10min and incidence of
hypotension (reduction in blood pressure of >30% of baseline) was recorded. The
use of vasopressor and occurrence of nausea/vomiting were also recorded. MAIN
RESULTS: 36 patients in SLOW group and 41 patients in FAST group were recruited
into the study. There was no significant difference in blood pressure drop of
>30% (p=0.497) between the two groups. There was no difference in the amount of
vasopressor used and incidence of nausea/vomiting in both groups. CONCLUSION: In
our study population, there was no difference in incidence of hypotension and
nausea/vomiting when spinal injection time is prolonged beyond 15s to 60s. TRIAL
REGISTRATION: ClinicalTrials.govNCT02275897. Registered on 15 October 2014.
PMID- 28494916
TI - Best practices for our most delicate patients.
PMID- 28494918
TI - Do we need another short-acting beta-blocker? A definite maybe....
PMID- 28494917
TI - Validation of the Nexfin(r) non-invasive continuous blood pressure monitoring
validated against Riva-Rocci/Korotkoff in a bariatric patient population.
AB - STUDY OBJECTIVE: The present study aimed to validate the Nexfin(r) monitor and to
assess the accuracy compared to classical sphygmomanometry (Riva-Rocci/Korotkoff
(RRK)) blood pressure (BP) measurements in patients with obesity scheduled for
bariatric surgery. DESIGN: Validation study. SETTING: Outpatient clinic for
bariatric surgery. PATIENTS: 33 patients scheduled for bariatric surgery.
MEASUREMENTS: The validation process was done according to the protocols
developed by the European Society of Hypertension from 2010. The Nexfin(r)
monitor (Edwards Lifesciences/BMEYE B.V., Amsterdam, The Netherlands) calculates
beat-to-beat blood pressure from finger pulse wave analysis. Measurements of
systolic and diastolic BP were obtained using classical sphygmomanometry and the
Nexfin(r) alternatingly. MAIN RESULTS: In total 99 pairs of BP measurements were
used. The device failed pass phase 1 as 65 systolic readings fell within 5mmHg
(73 required). And 61, 76 and 90 diastolic readings fell within 5, 10 and 15mmHg
respectively. Finally, it failed to pass phase 2 as 23 patients for systolic and
25 for diastolic had at least 2/3 of their comparisons falling within 5mmHg (24
required) but 10 subjects for systolic and 8 for diastolic had all three
comparisons more than 5mmHg different from the RRK readings (zero allowed). Mean
differences were 7.8+/-6.9mmHg for SBP and 8.0+/-7.2mmHg for DBP. CONCLUSION:
Using the revised protocol, the Nexfin(r) device was not able to pass validation.
However using the original protocol, the Nexfin(r) device passed phase 1 and 2.1
of the validation process and failed to pass phase 2.2.
PMID- 28494919
TI - Multimodal therapy facilitates a fast-track recovery after surgery - are
potential drug-drug interactions of clinical significance in the perioperative
period?
PMID- 28494921
TI - Proliferative diabetic retinopathy: laser or eye injection?
PMID- 28494920
TI - Clinical efficacy of intravitreal aflibercept versus panretinal photocoagulation
for best corrected visual acuity in patients with proliferative diabetic
retinopathy at 52 weeks (CLARITY): a multicentre, single-blinded, randomised,
controlled, phase 2b, non-inferiority trial.
AB - BACKGROUND: Proliferative diabetic retinopathy is the most common cause of severe
sight impairment in people with diabetes. Proliferative diabetic retinopathy has
been managed by panretinal laser photocoagulation (PRP) for the past 40 years. We
report the 1 year safety and efficacy of intravitreal aflibercept. METHODS: In
this phase 2b, single-blind, non-inferiority trial (CLARITY), adults (aged >=18
years) with type 1 or 2 diabetes and previously untreated or post-laser treated
active proliferative diabetic retinopathy were recruited from 22 UK ophthalmic
centres. Patients were randomly assigned (1:1) to repeated intravitreal
aflibercept (2 mg/0.05 mL at baseline, 4 weeks, and 8 weeks, and from week 12
patients were reviewed every 4 weeks and aflibercept injections were given as
needed) or PRP standard care (single spot or mutlispot laser at baseline,
fractionated fortnightly thereafter, and from week 12 patients were assessed
every 8 weeks and treated with PRP as needed) for 52 weeks. Randomisation was by
minimisation with a web-based computer generated system. Primary outcome
assessors were masked optometrists. The treating ophthalmologists and
participants were not masked. The primary outcome was defined as a change in best
corrected visual acuity at 52 weeks with a linear mixed-effect model that
estimated adjusted treatment effects at both 12 weeks and 52 weeks, having
excluded fluctuations in best corrected visual acuity owing to vitreous
haemorrhage. This modified intention-to-treat analysis was reapplied to the per
protocol participants. The non-inferiority margin was prespecified as -5 Early
Treatment Diabetic Retinopathy Study letters. Safety was assessed in all
participants. This trial is registered with ISRCTN registry, number 32207582.
FINDINGS: We recruited 232 participants (116 per group) between Aug 22, 2014 and
Nov 30, 2015. 221 participants (112 in aflibercept group, 109 in PRP group)
contributed to the modified intention-to-treat model, and 210 participants (104
in aflibercept group and 106 in PRP group) within per protocol. Aflibercept was
non-inferior and superior to PRP in both the modified intention-to-treat
population (mean best corrected visual acuity difference 3.9 letters [95% CI 2.3
5.6], p<0.0001) and the per-protocol population (4.0 letters [2.4-5.7],
p<0.0001). There were no safety concerns. The 95% CI adjusted difference between
groups was more than the prespecified acceptable margin of -5 letters at both 12
weeks and 52 weeks. INTERPRETATION: Patients with proliferative diabetic
retinopathy who were treated with intravitreal aflibercept had an improved
outcome at 1 year compared with those treated with PRP standard care. FUNDING:
The Efficacy and Mechanism Evaluation Programme, a Medical Research Council and
National Institute for Health Research partnership.
PMID- 28494922
TI - Analysis of JAK-STAT signaling pathway genes and their microRNAs in the
intestinal mucosa of genetically disparate chicken lines induced with necrotic
enteritis.
AB - The JAK-STAT signaling pathway plays a key role in cytokine and growth factor
activation and is involved in several cellular functions and diseases. The main
objective of this study was to investigate the expression of candidate JAK-STAT
pathway genes and their regulators and interactors in the intestinal mucosal
layer of two genetically disparate chicken lines [Marek's disease (MD)-resistant
line 6.3 and MD-susceptible line 7.2] induced with necrotic enteritis (NE).
Through RNA-sequencing, we investigated 116 JAK-STAT signaling pathway-related
genes that were significant and differentially expressed between the intestinal
mucosa of the two lines compared with respective uninfected controls. About 15
JAK-STAT pathway genes were further verified by qRT-PCR, and the results were in
agreement with our sequencing data. All the identified 116 genes were annotated
through Gene Ontology and mapped to the KEGG chicken JAK-STAT signaling pathway.
To the best of our knowledge, this is the first study to represent the
transcriptional analysis of a large number of candidate genes, regulators, and
potential interactors in the JAK-STAT pathway of the two chicken lines induced
with NE. Several key genes of the interactome, namely, STAT1/3/4, STAT5B, JAK1-3,
TYK2, AKT1/3, SOCS1-5, PIAS1/2/4, PTPN6/11, and PIK3, were determined to be
differentially expressed in the two lines. Moreover, we detected 68 known miRNAs
variably targeting JAK-STAT pathway genes and differentially expressed in the two
lines induced with NE. The RNA-sequencing and bioinformatics analyses in this
study provided an abundance of data that will be useful for future studies on JAK
STAT pathways associated with the functions of two genetically disparate chicken
lines induced with NE.
PMID- 28494923
TI - Effects of serum amyloid A on matrix metalloproteinase-9 production in feline
lymphoma-derived cell lines.
AB - Serum amyloid A (SAA) concentration and plasma matrix metalloproteinase-9 (MMP-9)
levels are increased in cats with lymphoma. In the present study, the association
between SAA and MMP-9 production was evaluated using recombinant feline SAA
(rfSAA) and three feline lymphoma-derived cell lines: 3201, MS4, and MCC. MMP-9
mRNA expression was significantly increased by rfSAA stimulation only in MCC
cells. Secreted MMP-9 protein in culture media was confirmed by gelatin
zymography, with clear bands of MMP-9 detected in MCC cells following rfSAA
stimulation. A significant increase in semi-quantified MMP-9 levels was observed
with 5 and 25MUg/ml of rfSAA stimulation. The infiltrative activities of feline
lymphoma cells, assessed by the matrigel transwell assay, showed that rfSAA
stimulated cell infiltration in MCC cells, in addition to MMP-9 expression.
Although the response to rfSAA stimulation varied between cell lines, the results
showed that rfSAA can stimulate MMP-9 production and infiltration of feline
lymphoma-derived cells. The findings of this study have identified a novel role
for SAA in the progression of some forms of feline lymphoma.
PMID- 28494924
TI - Loss of CD45 cell surface expression in canine T-zone lymphoma results from
reduced gene expression.
AB - Canine T-zone lymphoma (TZL) is a peculiar lymphoma subtype characterized by an
indolent clinical course and aberrant CD45-negative phenotype, commonly
recognized by flow cytometry (FC). Recent studies have described clinical
presentation and behavior, but to date the mechanisms behind the loss of CD45
protein expression have never been investigated. The aims of this study were: 1)
to confirm the absence of CD45 in canine TZL via the concomitant use of FC and
immunohistochemistry with two different sources of antibody; and 2) to
investigate the amount of CD45 transcript and the presence of CD45 gene in the
neoplastic cells of dogs affected by TZL. 57 lymph node aspirates were included
in the present study: 40 (70.2%) TZLs, 7 (12.3%) high grade T-cell lymphomas and
10 (17.5%) reactive lymph nodes. Neoplastic cells and normal T-cells were
isolated from TZL and reactive lymph nodes, respectively, via cell sorting.
Immunohistochemistry was performed on 2 TZL, 2 reactive lymph nodes and 2
Peripheral T-cell Lymphomas. Total RNA and genomic DNA were extracted from lymph
nodes aspirates. Two different quantitative real-time PCR experiments were
designed, to determine the amount of the CD45 transcript and of the corresponding
gene fragment. All TZL cases were negative for CD45 at immunohistochemistry. CD45
transcript amount was significantly lower in TZL compared to controls (p<0.001).
This difference was not significant (p=0.584) for CD45 DNA load, that was similar
between TZL and controls. Moreover, CD45 transcript amount was inversely
correlated with the percentage of neoplastic cells in each TZL sample (p=0.010).
These results confirm that CD45 protein is lacking on cell surface irrespective
of the technique and antibody source adopted. This phenotypic aberrancy is
apparently due to the absence of gene transcription, as CD45 DNA was present,
whereas CD45 transcript was virtually absent in the neoplastic cells. The data
here reported support further studies investigating possible factors impairing
CD45 gene transcription.
PMID- 28494925
TI - Comparison of humoral and T-cell-mediated immune responses to a single dose of
Bovela(r) live double deleted BVDV vaccine or to a field BVDV strain.
AB - The objective of this study was to determine and compare the humoral and cellular
immune responses of calves exposed to a single dose of Bovela(r) bovine viral
diarrhea virus (BVDV) live double deleted vaccine or a field strain virus (FSV)
of BVDV type 2 (strain 890). Thirty seronegative, colostrum-deprived 5 month-old
Holstein steer calves that tested negative for persistent BVDV by ear notch
immunohistochemistry and seronegative to BVDV types 1 and 2 were used. Calves
were screened by multi-parameter flow cytometry (MP-FCM) 1 week before
vaccination to ensure that they were negative for T cell responses to the BVDV
types 1 and 2 viruses in the Bovela(r) vaccine. Calves were assigned to 3
treatment groups: control (PBS), FSV inoculated, and Bovela(r) vaccinated. The
humoral response was tested by standard serum virus neutralization (SVN) test to
BVDV types 1 (Singer strain) and 2 (strain 125). The response by CD4, CD8, and
gamma delta (gammadelta TCR) T cells was evaluated by MP-FCM using individual
BVDV types 1 and 2 from Bovela(r) vaccine as recall antigens at 5, 6, and 7 weeks
after vaccination. Activation markers used were upregulation of surface CD25 (IL
2R), intracellular interferon gamma (IFNgamma) and intracellular interleukin 4
(IL-4). Each T cell subset was evaluated for increased expression of each
activation marker compared to non-antigen stimulated cells of the same animal.
All Bovela(r) vaccinated and FSV inoculated calves produced SVN antibodies to
both BVDV types 1 and 2 while control animals remained seronegative throughout
the study. The mean (weeks 5, 6, and 7) T cell recall responses to Bovela(r) BVDV
type 1 and type 2 recall antigens were numerically higher in all three T cell
subsets (CD4, CD8, and gammadelta TCR) for all three activation markers (CD25,
IFNgamma, and IL-4) when compared to either the control animals or to the FSV
inoculated animals. These differences were often, but not always, statistically
significant (P<0.05).
PMID- 28494926
TI - Gastrokine mRNA expression in gastric tissue from dogs with helicobacter
colonisation but without inflammatory change during treatment.
AB - Gastrokines (GKNs) are bioactive substances secreted by gastric cells. Evidence
supports functional roles for GKNs in gastric homeostasis, immune responses and
tumour suppression. Down-regulation has been reported in Helicobacter pylori
associated gastritis and other inflammatory gastrointestinal conditions in mice
and people. The aim of this study was to evaluate GKN gene expression in dogs
positive for other Helicobacter spp. both before and after treatment. Expression
of Gkn-1 and Gkn-2 mRNA was studied in endoscopic biopsy samples collected from
seven healthy dogs over three time-points pre- (T0) and at 1 and 18 weeks post
treatment for Helicobacter spp. colonisation (T1 & T2). The relative expression
software tool (REST) was used to provide efficiency corrected expression ratios
for comparisons between groups and these results were compared to a standard
2DeltaDeltaCT methodology. Compared with T1 Gkn1 and Gkn2 mRNA expression was
greater at T0 by a mean factor of 2.53 (SE=1.83-3.54) for Gkn1 (P=0.000) and 2.85
(SE=2.23-3.75) for Gkn2 (P=0.000). This difference was attenuated when
comparisons were made between T0 and T2. Histopathological evidence of gastritis
was not present in any Helicobacter spp. positive sample. When compared to post
eradication samples Gkn gene expression is increased in the presence of
Helicobacter spp. in dogs without evidence for concurrent inflammation. Further
evaluation is required to determine the relevance of this finding, however given
a suspected role in gastric homeostasis, up-regulation of GKN1 and GKN2 could
limit development of gastritis in Helicobacter spp. positive dogs.
PMID- 28494927
TI - Comparison of interferon and bovine herpesvirus-1-specific IgA levels in nasal
secretions of dairy cattle administered an intranasal modified live viral vaccine
prior to calving or on the day of calving.
AB - Thirty-two Holstein cows were allocated to receive intranasal vaccination with
modified live bovine herpesvirus-1 (BHV-1), bovine respiratory syncytial virus
(BRSV) and parainfluenza type 3 virus (PI3V) vaccine either two weeks prior to
their projected calving date, or within 24h after calving. Nasal secretions were
collected twice at a 12-h interval on the day prior to vaccination (day 0) and at
2, 4, 7, 10 and 14days post vaccination to measure interferon (IFN) alpha, IFN
beta, IFN-gamma, and BHV-1-specific IgA by ELISA. Serum neutralizing antibody
titers to BHV-1 and BRSV were measured on days 0, 7, and 14. There was a
significant treatment effect (p<0.0004) and interaction (p<0.05) on nasal BHV-1
IgA levels, with higher IgA levels in cows vaccinated within 24h after calving.
There was a significant treatment effect on nasal IFN-gamma concentration
(p<0.05) and on nasal total IFN concentration (p<0.05), with higher IFN-gamma and
total IFN concentrations seen in cows vaccinated within 24h after calving. There
was no significant treatment or interaction effect on nasal IFN-alpha or IFN-beta
concentrations, or on serum neutralizing titers to BRSV. In spite of prior viral
vaccination during the previous lactation, cows vaccinated on the day of calving
responded to an intranasal viral vaccination with increased concentrations of IFN
gamma and increased titers of IgA following vaccination which was significantly
higher than cows vaccinated precalving. This study is the first to examine
respiratory mucosal responses in immunologically mature dairy cattle vaccinated
intranasally before and after calving.
PMID- 28494928
TI - Shotgun proteomic analysis of the secretome of bovine endometrial mesenchymal
progenitor/stem cells challenged or not with bacterial lipopolysaccharide.
AB - The use of the conditioned medium (CM) for diseases treatment is based on its
enrichment with biomolecules with therapeutic properties and themselves have a
beneficial effect. Secretome of bovine endometrial mesenchymal progenitor/stem
cells (eMSCs) using a proteomics approach is until now unknown. This work aimed
to evaluate the secretome of bovine eMSCs-CM challenged or not with
lipopolysaccharide (LPS). For this, eMSCs characterized were challenged (TG) or
not (CG). The CM was collected 12h after stimulation and submitted to mass
spectrometry analysis. The classification of identified proteins was done by
PANTHER according to biological processes, molecular function, cellular component
and protein class. 397 protein groups were identified in TG and 302 in CG. We
observed positive enrichment for antibacterial response proteins, macrophage
activation function, receptor-mediated endocytosis, hydrolase activity,
inhibitory enzyme in TG, and for activity structural molecule and intermediate
filament cytoskeleton in the CG. Our experimental model shows that eMSCs respond
to LPS in the concentration used and can be used to study immune-inflammatory
response, besides of the secretion of proteins mainly related to tissue
remodeling, immune response and angiogenesis which is an interesting feature for
use in cell therapy.
PMID- 28494929
TI - Investigation of corneal autoantibodies in horses with immune mediated keratitis
(IMMK).
AB - Immune mediated keratitis (IMMK) is primarily a non-ulcerative keratitis in
horses causing intermittent ocular pain, eventually resulting in visual
impairment. Affected horses typically respond to immunomodulatory treatment.
However, the underlying cause of the disease remains enigmatic. The current study
was undertaken to investigate the presence of autoantibodies in horses with
immune mediated keratitis. Using 28 horses with IMMK and 27 healthy controls
screening for serum autoantibodies against the corneal proteome using indirect
immunofluorescence, one-dimensional (1DE) and two-dimensional electrophoresis
(2DE) with subsequent western blot analysis was performed followed by mass
spectrometric identification of bands or spots of interest. Indirect
immunofluorescence did not reveal a difference in immune response towards corneal
proteins between healthy horses and those with IMMK. Using western blot analysis
some horses affected by IMMK (4/28) showed a single band (1D) or a single spot
(2DE) (5/28) not detected in healthy controls. The corresponding spot was
identified as maspin (SERPINB5), a protein responsible for the inhibition of
corneal vascularisation, cell migration and cell adhesion to the extracellular
matrix. Tests with a recombinant human protein commercially available did not
verify blot findings, but the human protein may not be fully cross-reactive.
Still, maspin might play a role in some cases of equine IMMK. Further research is
needed to clarify the etiology of this disease.
PMID- 28494931
TI - Hemophagocytic lymphohistiocytosis in acute African swine fever clinic.
AB - INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) usually has been defined
as the combination of a proliferation of cytologically benign, actively
phagocytic macrophages in bone marrow, spleen, lymph nodes, etc. in association
with fever, cytopenia, splenomegaly, and hypertriglyceridemia. HLH is often
triggered by viral infection. The aim of this study was to ascertain the features
of HLH involvement in African swine fever virus (ASFV) (genotype II)
pathogenesis. METHODS: The serum levels of macrophage colony-stimulating factor
(MCSF) and granulocyte-macrophage colony-stimulating factor (GMCSF), as well as
the histological constitution (for hemophagocytic macrophages detection) of
various organs of pigs infected with ASFV genotype II were investigated. The
diagnosis of HLH was made according to universally accepted human criteria.
RESULTS: The association of fever, cytopenias, splenomegaly, and hemophagocytosis
was present in 87.5% of the infected pigs (absence of hyperthermia in one of
eight pigs). Marked hypertriglyceridemia was observed at 3-4days post infection.
Previously it was shown that ASFV induced a significant decrease in the level of
fibrinogen from day 5 till the end of experiment. Progression of the HLH
coincided with a temporary increase in the serum levels of MCSF levels (early
stage of disease) and GMCSF levels (2-3 pays post infection). CONCLUSIONS:
Hemophagocytic syndrome should be suspected in ASFV (genotypeII) infected pigs.
PMID- 28494930
TI - A ROS-dependent and Caspase-3-mediated apoptosis in sheep bronchial epithelial
cells in response to Mycoplasma Ovipneumoniae infections.
AB - Mycoplasma Ovipneumoniae (M. ovipneumoniae) is a primary etiological agent of
enzootic pneumonia in sheep and goats. It can enter and colonize ovine
respiratory epithelial cells to establish an infection, which leads a serious
cell death of epithelial cells. However, the nature of the interaction between
pathogen of M. ovipneumoniae and host cells in the cell injury is currently not
well understood. In this study, we investigated the epithelial cell apoptosis
caused by an infection of M. ovipneumoniae in sheep primary air-liquid interface
(ALI) epithelial cultures. The results showed that M. ovipneumoniae could
specifically bind to ciliated cells at early stage of infection. Flow cytometric
analysis demonstrated that an infection of M. ovipneumoniae induced a time
dependent cell apoptotic cell death, accompanied with an increased production of
extracellular nitric oxide (NO), intracellular reactive oxygen species (ROS)
production and activation of caspase-3 signaling in sheep bronchial epithelial
cells. The induced cell apoptosis was further confirmed by a transferase-mediated
deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) assay. Interestingly,
the M. ovipneumoniae-induced apoptosis and activation of caspase-3 were
correlated with the production of ROS but not NO. Mechanistically, M.
ovipneumoniae-induced cell apoptosis was mediated by a mechanism by increasing
the expression of phosphorylation of p38 and pro-apoptotic proteins, and
activating caspase-3, caspase-8 and poly ADP-ribose polymerase (PARP) cleavage.
These results suggest a ROS-dependent and caspase-3-mediated cell apoptosis in
sheep bronchial epithelial cells in response to M. ovipneumoniae infections.
PMID- 28494932
TI - Comparison of growth performance and immune parameters of three commercial
chicken lines used in organic production.
AB - Owing to the higher demands for avoiding medication and antibiotics, health
status of the production animals plays an important role in the poultry industry,
especially in organic poultry systems. Immunity plays a major role in keeping the
host free from disease, and it is evident that the host's genetic make-up
influences immunity and disease resistance/susceptibility in chickens.
Previously, breeding strategies aimed at selection for resistance against
specific diseases with the risk of creating less disease resistance against other
pathogens. Changing breeding strategies towards selection of chickens with a more
general and broad disease resistance or robustness may therefore improve the
overall health status, animal welfare, and food security in the poultry
production. The aim of this study was therefore to compare the immunocompetence
of the presumed "robust" Hellevad chickens with two chicken lines widely used in
organic production, Bovans Brown (Bovans) and Hisex White (Hisex). The chickens
were subjected to a routine vaccination program comprising one parasite and four
viral vaccines. The current study indicates that considerable differences in
immunocompetence may exist between commercial layer lines used in organic
production. The Hellevad chickens were found to have higher body weight at the
end of the experiment (17 weeks of age) than the other two lines. Furthermore,
Hellevad and Hisex chickens were found to have higher levels of humoral innate
immunity with regard to sample to positive ratio of natural antibodies in serum
and concentration of mannose-binding lectin in serum as compared to Bovans.
Moreover, indications of an inflammatory response were observed in the Bovans at
week 5, corresponding to 1 week after vaccination with live infectious bursal
disease virus. With regard to adaptive immune parameters such as IgY
concentration in blood and infectious bursal disease virus (IBDV)-specific
antibody titres, the Hellevad and Hisex chickens had lower levels than the
Bovans. How the differences observed in growth and immune parameters in the three
chicken lines influence the immune protection against infection needs to be
studied further.
PMID- 28494933
TI - Comparative phenotypic and functional analyses of the effects of autologous
plasma and recombinant human macrophage-colony stimulating factor (M-CSF) on
porcine monocyte to macrophage differentiation.
AB - Porcine monocyte-derived macrophages (moMPhi) have been employed as a model cell
in numerous studies of the porcine immune system. However, the lack of a
standardized method for moMPhi differentiation hampers the comparison of results
coming from the use of different laboratory protocols. In this study we compared
the use of varying concentrations of autologous plasma (10, 20 and 30% v/v) or
recombinant human macrophage-colony stimulating factor (hM-CSF; 50, 100, and
200ng/ml) to differentiate porcine monocytes into macrophages. Changes in cell
morphology and surface marker expression were assessed by confocal microscopy and
flow cytometry. Macrophage differentiation was evaluated by analysing TNF-alpha
response to LPS stimulation and determining cytokine secretion patterns under
both basal conditions and after classical and alternative activation. The effects
of the differentiation methods on metabolic activity and susceptibility to
infection with the myelotropic African swine fever virus (ASFV) were also
evaluated. Monocytes cultured using the different culture conditions tested
augmented in dimension and cellular complexity, but increasing porcine plasma
concentrations resulted in a dose dependent enhancement in granularity and a
marked pleomorphism. As expected, CD163, MHC class II DR and CD203a expression
were up-regulated in both hM-CSF (M-CSF-moMPhi) and autologous plasma cultured
macrophages (AP-moMPhi), although a lower percentage of CD163+ cells were found
following differentiation with high percentages of porcine plasma. We observed
enhanced number of viable cells using high concentration of hM-CSF compared to
porcine plasma, suggesting a proliferative effect. Irrespective of
differentiation conditions, monocyte differentiation into macrophages resulted in
an increased susceptibility to ASFV and yielded larger amounts of LPS-induced TNF
alpha. AP-moMPhi showed a higher basal release of IL-1RA compared to those
cultured with hM-CSF and displayed a reduced ability to respond to classical
activation, suggesting that the use of high percentages of porcine plasma led to
the acquisition of a M2-like phenotype. We conclude that all the protocols tested
in this study can be considered as suitable to produce porcine moMPhi, although
the use of hM-CSF provides high responsiveness to M1 polarization. Since a higher
phenotypic and functional inter-animal variability was observed in AP-moMPhi, we
propose that the use of low concentration of hM-CSF should be adopted as the
method of choice to provide a better reproducibility between experiments.
PMID- 28494934
TI - The expression of NKG2D on porcine IEL and its possible relation to the adaptive
intestinal immune system.
AB - The gastrointestinal tract contains a multitude of components which include
intraepithelial lymphocytes (IEL). IELs have been reported to express a variety
of surface receptors that enable cross talk among various cell populations. The
purpose of the reported investigation was to determine which IEL populations
express the natural killer cell receptor NKG2D which is an activating receptor
that plays a role in cytolytic responses. In a feeding experiment with piglets,
IELs were isolated from jejunal tissue at three different stages post weaning.
The time dependent development of different cell populations was evaluated and an
elevated number of lymphocytes (CD45+) shortly after weaning was observed
compared to later time points. The number of T cells (CD3), including cytotoxic T
cells (CD8beta/CD16-), appeared to be particularly affected by the weaning
period. Correlation analysis revealed an association between the NKG2D expression
in jejunal tissue and the frequency of lymphocytes, esp. CD8beta+ cytotoxic T
cells. Gene expression analysis of NKG2D were performed on several isolated IEL
populations and support the hypothesis that cytotoxic T cells (CD8beta) in the
porcine gut epithelium are capable of communicating with the surrounding
enterocytes and inducing immune reactions via NKG2D. Unlike previous observations
in porcine blood, the gammadelta T cells of the gut epithelium also showed
expression of the stress factor binding NKG2D receptor. Subsequent analysis of
the isolated IELs revealed that T cells appear to only express the receptor after
isolation with an anti-CD3 mab, indicating that a previous stimulation of the
TCR/CD3 complex may reinforce this signal transduction pathway.
PMID- 28494935
TI - Corrigendum to "Transplantation of VEGFl65-overexpressing vascular endothelial
progenitor cells relieves endothelial injury after deep vein thrombectomy"
[Thromb. Res. 137 (2016) 41-45].
PMID- 28494936
TI - Functional Analysis of Dendritic Cells Generated from T-iPSCs from CD4+ T Cell
Clones of Sjogren's Syndrome.
AB - Although it is important to clarify the pathogenic functions of T cells in human
samples, their examination is often limited due to difficulty in obtaining
sufficient numbers of dendritic cells (DCs), used as antigen-presenting cells,
especially in autoimmune diseases. We describe the generation of DCs from induced
pluripotent stem cells derived from T cells (T-iPSCs). We reprogrammed CD4+ T
cell clones from a patient with Sjogren's syndrome (SS) into iPSCs, which were
differentiated into DCs (T-iPS-DCs). T-iPS-DCs had dendritic cell-like
morphology, and expressed CD11c, HLA-DR, CD80, CD86, and also BDCA-3. Compared
with monocyte-derived DCs, the capacity for antigen processing was similar, and T
iPS-DCs induced the proliferative response of autoreactive CD4+ T cells.
Moreover, we could evaluate T cell functions of the patient with SS. In
conclusion, we obtained adequate numbers of DCs from T-iPSCs, which could be used
to characterize pathogenic T cells in autoimmune diseases such as SS.
PMID- 28494937
TI - MSC-derived Extracellular Vesicles Attenuate Immune Responses in Two Autoimmune
Murine Models: Type 1 Diabetes and Uveoretinitis.
AB - Accumulating evidence shows that extracellular vesicles (EVs) produced by
mesenchymal stem/stromal cells (MSCs) exert their therapeutic effects in several
disease models. We previously demonstrated that MSCs suppress autoimmunity in
models of type 1 diabetes (T1D) and experimental autoimmune uveoretinitis (EAU).
Therefore, here, we investigated the therapeutic potential of MSC-derived EVs
using our established mouse models for autoimmune diseases affecting the pancreas
and the eye: T1D and EAU. The data demonstrate that MSC-derived EVs effectively
prevent the onset of disease in both T1D and EAU. In addition, the mixed
lymphocyte reaction assay with MSC-derived EVs indicated that EVs inhibit
activation of antigen-presenting cells and suppress development of T helper 1
(Th1) and Th17 cells. These results raise the possibility that MSC-derived EVs
may be an alternative to cell therapy for autoimmune disease prevention.
PMID- 28494938
TI - PI3K/AKT/mTOR Signaling Mediates Valproic Acid-Induced Neuronal Differentiation
of Neural Stem Cells through Epigenetic Modifications.
AB - Although valproic acid (VPA), has been shown to induce neuronal differentiation
of neural stem cells (NSCs), the underlying mechanisms remain poorly understood.
Here we investigated if and how mammalian target of rapamycin (mTOR) signaling is
involved in the neuronal differentiation of VPA-induced NSCs. Our data
demonstrated that mTOR activation not only promoted but also was necessary for
the neuronal differentiation of NSCs induced by VPA. We further found that
inhibition of mTOR signaling blocked demethylation of neuron-specific gene
neurogenin 1 (Ngn1) regulatory element in induced cells. These are correlated
with the significant alterations of passive DNA demethylation and the active DNA
demethylation pathway in the Ngn1 promoter, but not the suppression of lysine
specific histone methylation and acetylation in the promoter region of Ngn1.
These findings highlight a potentially important role for mTOR signaling, by
working together with DNA demethylation, to influence the fate of NSCs via
regulating the expression of Ngn1 in VPA-induced neuronal differentiation of
NSCs.
PMID- 28494939
TI - Cardiosphere-Derived Cells Require Endoglin for Paracrine-Mediated Angiogenesis.
AB - Clinical trials of stem cell therapy to treat ischemic heart disease primarily
use heterogeneous stem cell populations. Small benefits occur via paracrine
mechanisms that include stimulating angiogenesis, and increased understanding of
these mechanisms would help to improve patient outcomes. Cardiosphere-derived
cells (CDCs) are an example of these heterogeneous stem cell populations,
cultured from cardiac tissue. CDCs express endoglin, a co-receptor that binds
specific transforming growth factor beta (TGFbeta) family ligands, including bone
morphogenetic protein 9 (BMP9). In endothelial cells endoglin regulates
angiogenic responses, and we therefore hypothesized that endoglin is required to
promote the paracrine pro-angiogenic properties of CDCs. Cre/LoxP technology was
used to genetically manipulate endoglin expression in CDCs, and we found that the
pro-angiogenic properties of the CDC secretome are endoglin dependent both in
vitro and in vivo. Importantly, BMP9 pre-treatment of endoglin-depleted CDCs
restores their pro-angiogenic paracrine properties. As BMP9 signaling is normally
required to maintain endoglin expression, we propose that media containing BMP9
could be critical for therapeutic CDC preparation.
PMID- 28494940
TI - Differentiation-Defective Human Induced Pluripotent Stem Cells Reveal Strengths
and Limitations of the Teratoma Assay and In Vitro Pluripotency Assays.
AB - The ability to form teratomas in vivo containing multiple somatic cell types is
regarded as functional evidence of pluripotency for human pluripotent stem cells
(hPSCs). Since the Teratoma assay is animal dependent, laborious, and only
qualitative, the PluriTest and the hPSC ScoreCard assay have been developed as in
vitro alternatives. Here we compared normal hPSCs, induced hPSCs (hiPSCs) with
reactivated reprogramming transgenes, and human embryonal carcinoma cells (hECs)
in these assays. While normal hPSCs gave rise to typical teratomas, the
xenografts of the hECs and the hiPSCs with reactivated reprogramming transgenes
were largely undifferentiated and malignant. The hPSC ScoreCard assay confirmed
the line-specific differentiation propensities in vitro. However, when
undifferentiated cells were analyzed by the PluriTest, only hECs were identified
as abnormal whereas all other cell lines were indistinguishable and resembled
normal hPSCs. Our results indicate that pluripotency assays are best selected on
the basis of intended downstream applications.
PMID- 28494941
TI - Efficient Recreation of t(11;22) EWSR1-FLI1+ in Human Stem Cells Using
CRISPR/Cas9.
AB - Efficient methodologies for recreating cancer-associated chromosome
translocations are in high demand as tools for investigating how such events
initiate cancer. The CRISPR/Cas9 system has been used to reconstruct the genetics
of these complex rearrangements at native loci while maintaining the architecture
and regulatory elements. However, the CRISPR system remains inefficient in human
stem cells. Here, we compared three strategies aimed at enhancing the efficiency
of the CRISPR-mediated t(11;22) translocation in human stem cells, including
mesenchymal and induced pluripotent stem cells: (1) using end-joining DNA
processing factors involved in repair mechanisms, or (2) ssODNs to guide the
ligation of the double-strand break ends generated by CRISPR/Cas9; and (3) all-in
one plasmid or ribonucleoprotein complex-based approaches. We report that the
generation of targeted t(11;22) is significantly increased by using a combination
of ribonucleoprotein complexes and ssODNs. The CRISPR/Cas9-mediated generation of
targeted t(11;22) in human stem cells opens up new avenues in modeling Ewing
sarcoma.
PMID- 28494943
TI - Kinematic analysis of the scaphoid using gated four-dimensional CT.
AB - AIM: To investigate the kinematics of the scaphoid while the wrist was in
radioulnar motion using gated four-dimensional computed tomography (4DCT)
imaging. MATERIALS AND METHODS: Six cadaveric wrist specimens were scanned in the
following order of capsulotomy and ligament sectioning: (1) ligaments intact, (2)
capsulotomy, (3) scapholunate ligament division, and lastly, (4) lunotriquetral
ligament division. A three-dimensional model was then reconstructed to analyse
the translation and angular displacements of the scaphoid. RESULTS: The magnitude
of displacement was found to increase with each consecutive ligament sectioning.
Translation along the y-axis was statistically significant, with the scaphoid
shifting up to 1.39 mm from its original position after complete sectioning of
the ligaments while the wrist was deviating radially. Angular displacement about
all three axes was statistically significant, with the highest occurring in the
flexion-extension plane when the scaphoid flexed by 9.1 degrees from its
original position after total sectioning of the ligaments. CONCLUSION: The
present study showed that changes in the kinematics of the scaphoid can be
detected using 4DCT, thus demonstrating its feasibility in the diagnosis of
dynamic carpal instability, which only presents during motion.
PMID- 28494942
TI - RNA Polymerase III Subunit POLR3G Regulates Specific Subsets of PolyA+ and
SmallRNA Transcriptomes and Splicing in Human Pluripotent Stem Cells.
AB - POLR3G is expressed at high levels in human pluripotent stem cells (hPSCs) and is
required for maintenance of stem cell state through mechanisms not known in
detail. To explore how POLR3G regulates stem cell state, we carried out deep
sequencing analysis of polyA+ and smallRNA transcriptomes present in hPSCs and
regulated in POLR3G-dependent manner. Our data reveal that POLR3G regulates a
specific subset of the hPSC transcriptome, including multiple transcript types,
such as protein-coding genes, long intervening non-coding RNAs, microRNAs and
small nucleolar RNAs, and affects RNA splicing. The primary function of POLR3G is
in the maintenance rather than repression of transcription. The majority of
POLR3G polyA+ transcriptome is regulated during differentiation, and the key
pluripotency factors bind to the promoters of at least 30% of the POLR3G
regulated transcripts. Among the direct targets of POLR3G, POLG is potentially
important in sustaining stem cell status in a POLR3G-dependent manner.
PMID- 28494944
TI - How to Make a Worm Twitch.
PMID- 28494945
TI - Tug of War at the Cell-Matrix Interface.
PMID- 28494947
TI - AESOP: A Python Library for Investigating Electrostatics in Protein Interactions.
AB - Electric fields often play a role in guiding the association of protein
complexes. Such interactions can be further engineered to accelerate complex
association, resulting in protein systems with increased productivity. This is
especially true for enzymes where reaction rates are typically diffusion limited.
To facilitate quantitative comparisons of electrostatics in protein families and
to describe electrostatic contributions of individual amino acids, we previously
developed a computational framework called AESOP. We now implement this
computational tool in Python with increased usability and the capability of
performing calculations in parallel. AESOP utilizes PDB2PQR and Adaptive Poisson
Boltzmann Solver to generate grid-based electrostatic potential files for protein
structures provided by the end user. There are methods within AESOP for
quantitatively comparing sets of grid-based electrostatic potentials in terms of
similarity or generating ensembles of electrostatic potential files for a library
of mutants to quantify the effects of perturbations in protein structure and
protein-protein association.
PMID- 28494946
TI - Tropomodulins and Leiomodins: Actin Pointed End Caps and Nucleators in Muscles.
AB - Cytoskeletal structures characterized by actin filaments with uniform lengths,
including the thin filaments of striated muscles and the spectrin-based membrane
skeleton, use barbed and pointed-end capping proteins to control subunit
addition/dissociation at filament ends. While several proteins cap the barbed
end, tropomodulins (Tmods), a family of four closely related isoforms in
vertebrates, are the only proteins known to specifically cap the pointed end.
Tmods are ~350 amino acids in length, and comprise alternating tropomyosin- and
actin-binding sites (TMBS1, ABS1, TMBS2, and ABS2). Leiomodins (Lmods) are
related in sequence to Tmods, but display important differences, including most
notably the lack of TMBS2 and the presence of a C-terminal extension featuring a
proline-rich domain and an actin-binding WASP-Homology 2 domain. The Lmod
subfamily comprises three somewhat divergent isoforms expressed predominantly in
muscle cells. Biochemically, Lmods differ from Tmods, acting as powerful
nucleators of actin polymerization, not capping proteins. Structurally, Lmods and
Tmods display crucial differences that correlate well with their different
biochemical activities. Physiologically, loss of Lmods in striated muscle results
in cardiomyopathy or nemaline myopathy, whereas complete loss of Tmods leads to
failure of myofibril assembly and developmental defects. Yet, interpretation of
some of the in vivo data has led to the idea that Tmods and Lmods are
interchangeable or, at best, different variants of two subfamilies of pointed-end
capping proteins. Here, we review and contrast the existing literature on Tmods
and Lmods, and propose a model of Lmod function that attempts to reconcile the in
vitro and in vivo data, whereby Lmods nucleate actin filaments that are
subsequently capped by Tmods during sarcomere assembly, turnover, and repair.
PMID- 28494948
TI - Microvessel Chaste: An Open Library for Spatial Modeling of Vascularized Tissues.
AB - Spatial models of vascularized tissues are widely used in computational
physiology. We introduce a software library for composing multiscale,
multiphysics models for applications including tumor growth, angiogenesis,
osteogenesis, coronary perfusion, and oxygen delivery. Composition of such models
is time consuming, with many researchers writing custom software. Recent advances
in imaging have produced detailed three-dimensional (3D) datasets of vascularized
tissues at the scale of individual cells. To fully exploit such data there is an
increasing need for software that allows user-friendly composition of efficient,
3D models of vascularized tissues, and comparison of predictions with in vivo or
in vitro experiments and alternative computational formulations. Microvessel
Chaste can be used to build simulations of vessel growth and adaptation in
response to mechanical and chemical stimuli; intra- and extravascular transport
of nutrients, growth factors and drugs; and cell proliferation in complex 3D
geometries. In addition, it can be used to develop custom software for
integrating modeling with experimental data processing workflows, facilitated by
a comprehensive Python interface to solvers implemented in C++. This article
links to two reproducible example problems, showing how the library can be used
to build simulations of tumor growth and angiogenesis with realistic vessel
networks.
PMID- 28494949
TI - Molecular Counting with Localization Microscopy: A Bayesian Estimate Based on
Fluorophore Statistics.
AB - Superresolved localization microscopy has the potential to serve as an accurate,
single-cell technique for counting the abundance of intracellular molecules.
However, the stochastic blinking of single fluorophores can introduce large
uncertainties into the final count. Here we provide a theoretical foundation for
applying superresolved localization microscopy to the problem of molecular
counting based on the distribution of blinking events from a single fluorophore.
We also show that by redundantly tagging single molecules with multiple, blinking
fluorophores, the accuracy of the technique can be enhanced by harnessing the
central limit theorem. The coefficient of variation then, for the number of
molecules M estimated from a given number of blinks B, scales like ~1/Nl, where
Nl is the mean number of labels on a target. As an example, we apply our theory
to the challenging problem of quantifying the cell-to-cell variability of plasmid
copy number in bacteria.
PMID- 28494950
TI - Simultaneous Determination of Two Subdomain Folding Rates Using the "Transfer
Quench" Method.
AB - The investigation of the mechanism of protein folding is complicated by the
context dependence of the rates of intramolecular contact formation. Methods
based on site-specific labeling and ultrafast spectroscopic detection of
fluorescence signals were developed for monitoring the rates of individual
subdomain folding transitions in situ, in the context of the whole molecule.
However, each site-specific labeling modification might affect rates of folding
of near-neighbor structural elements, and thus limit the ability to resolve fine
differences in rates of folding of these elements. Therefore, it is highly
desirable to be able to study the rates of folding of two or more neighboring
subdomain structures using a single mutant to facilitate resolution of the order
and interdependence of such steps. Here, we report the development of the
"Transfer-Quench" method for measuring the rate of formation of two structural
elements using a single triple-labeled mutant. This method is based on Forster
resonance energy transfer combined with fluorescence quenching. We placed the
donor and acceptor at the loop ends, and a quencher at an alpha-helical element
involved in the node forming the loop. The folding of the triple-labeled mutant
is monitored by the acceptor emission. The formation of nonlocal contact (loop
closure) increases the time-dependent acceptor emission, while the closure of the
labeled helix turn reduces this emission. The method was applied in a study of
the folding mechanism of the common model protein, the B domain of staphylococcal
protein A. Only natural amino acids were used as probes, and thus possible
structural perturbations were minimized. Tyr and Trp residues served as donor and
acceptor at the ends of a long loop between helices I and II, and a Cys residue
as a quencher for the acceptor. We found that the closure of the loop (segment 14
33) occurs with the same rate constant as the nucleation of helix HII (segment 33
29), in line with the nucleation-condensation model.
PMID- 28494951
TI - The N-Terminal Domain of Ribosomal Protein L9 Folds via a Diffuse and Delocalized
Transition State.
AB - The N-terminal domain of L9 (NTL9) is a 56-residue mixed alpha-beta protein that
lacks disulfides, does not bind cofactors, and folds reversibly. NTL9 has been
widely used as a model system for experimental and computational studies of
protein folding and for investigations of the unfolded state. The role of side
chain interactions in the folding of NTL9 is probed by mutational analysis. phi
values, which represent the ratio of the change in the log of the folding rate
upon mutation to the change in the log of the equilibrium constant for folding,
are reported for 25 point mutations and 15 double mutants. All phi-values are
small, with an average over all sites probed of only 0.19 and a largest value of
0.4. The effect of modulating unfolded-state interactions is studied by measuring
phi-values in second- site mutants and under solvent conditions that perturb
unfolded-state energetics in a defined way. Neither of these alterations
significantly affects the distribution of phi-values. The results, combined with
those of earlier studies that probe the role of hydrogen-bond formation in
folding and the burial of surface area, reveal that the transition state for
folding contains extensive backbone structure and buries a significant fraction
of hydrophobic surface area, but lacks well developed side-chain-side-chain
interactions. The folding transition state for NTL9 does not contain a specific
"nucleus" consisting of a few key residues; rather, it involves extensive
backbone hydrogen bonding and partially formed structure delocalized over almost
the entire domain. The potential generality of these observations is discussed.
PMID- 28494952
TI - Fast Protein Translation Can Promote Co- and Posttranslational Folding of
Misfolding-Prone Proteins.
AB - Chemical kinetic modeling has previously been used to predict that fast
translating codons can enhance cotranslational protein folding by helping to
avoid misfolded intermediates. Consistent with this prediction, protein
aggregation in yeast and worms was observed to increase when translation was
globally slowed down, possibly due to increased cotranslational misfolding.
Observation of similar behavior in molecular simulations would confirm
predictions from the simpler chemical kinetic model and provide a molecular
perspective on cotranslational folding, misfolding, and the impact of translation
speed on these processes. All-atom simulations cannot reach the timescales
relevant to protein synthesis, and most conventional structure-based coarse
grained models do not allow for nonnative structure formation. Here, we introduce
a protocol to incorporate misfolding using the functional forms of publicly
available force fields. With this model we create two artificial proteins that
are capable of undergoing structural transitions between a native and a misfolded
conformation and simulate their synthesis by the ribosome. Consistent with the
chemical kinetic predictions, we find that rapid synthesis of misfolding-prone
nascent-chain segments increases the fraction of folded proteins by kinetically
partitioning more molecules through on-pathway intermediates, decreasing the
likelihood of sampling misfolded conformations. Novel to this study, to our
knowledge, we observe that differences in protein dynamics, arising from
different translation-elongation schedules, can persist long after the nascent
protein has been released from the ribosome, and that a sufficient level of
energetic frustration is needed for fast-translating codons to be beneficial for
folding. These results provide further evidence that fast-translating codons can
be as biologically important as pause sites in coordinating cotranslational
folding.
PMID- 28494953
TI - Analysis of O2-binding Sites in Proteins Using Gas-Pressure NMR Spectroscopy:
Outer Surface Protein A.
AB - Internal cavities in proteins produce conformational fluctuations and enable the
binding of small ligands. Here, we report a NMR analysis of O2-binding sites by
O2-induced paramagnetic relaxation enhancements (PREs) on amide groups of
proteins in solution. Outer surface protein A contains a nonglobular single-layer
beta-sheet that connects the N- and C-terminal globular domains. Several cavities
have been observed in both domains of the crystallized protein structure. The
receptor-binding sites are occluded and line the largest cavity of the C-terminal
domain. We observed significant O2-induced PREs for amide protons located around
the largest cavity and at the central beta-sheet. We suggested three potential O2
accessible sites in the protein based on the 1/r6 distance dependence of the PRE.
Two sites were in or close to the largest cavity and the third site was in the
surface crevice of the central beta-sheet. These results provide, to our
knowledge, the first evidence of ligand binding to the surface crevice and cavity
of the protein in solution. Because O2 generally binds more specifically to
hydrophobic rather than hydrophilic cavities within a protein, the results also
indicated that the receptor-binding sites lining the largest cavity were in the
hydrophobic environment in the ground-state conformation. Molecular dynamics
simulations permitted the visualization of the rotational and translational
motions of O2 within the largest cavity, egress of O2 from the cavity, and
ingress of O2 in the surface crevice of the beta-sheet. These molecular dynamics
simulation results qualitatively explained the O2-induced changes in NMR
observations. Exploring cavities that are sufficiently dynamic to enable access
by small molecules can be a useful strategy for the design of stable proteins and
their ligands.
PMID- 28494954
TI - Competing Pathways and Multiple Folding Nuclei in a Large Multidomain Protein,
Luciferase.
AB - Proteins obtain their final functional configuration through incremental folding
with many intermediate steps in the folding pathway. If known, these intermediate
steps could be valuable new targets for designing therapeutics and the sequence
of events could elucidate the mechanism of refolding. However, determining these
intermediate steps is hardly an easy feat, and has been elusive for most
proteins, especially large, multidomain proteins. Here, we effectively map part
of the folding pathway for the model large multidomain protein, Luciferase, by
combining single-molecule force-spectroscopy experiments and coarse-grained
simulation. Single-molecule refolding experiments reveal the initial nucleation
of folding while simulations corroborate these stable core structures of
Luciferase, and indicate the relative propensities for each to propagate to the
final folded native state. Both experimental refolding and Monte Carlo
simulations of Markov state models generated from simulation reveal that
Luciferase most often folds along a pathway originating from the nucleation of
the N-terminal domain, and that this pathway is the least likely to form
nonnative structures. We then engineer truncated variants of Luciferase whose
sequences corresponded to the putative structure from simulation and we use
atomic force spectroscopy to determine their unfolding and stability. These
experimental results corroborate the structures predicted from the folding
simulation and strongly suggest that they are intermediates along the folding
pathway. Taken together, our results suggest that initial Luciferase refolding
occurs along a vectorial pathway and also suggest a mechanism that chaperones may
exploit to prevent misfolding.
PMID- 28494955
TI - Environmental Calcium Controls Alternate Physical States of the Caulobacter
Surface Layer.
AB - Surface layers (S-layers) are paracrystalline, proteinaceous structures found in
most archaea and many bacteria. Often the outermost cell envelope component, S
layers serve diverse functions including aiding pathogenicity and protecting
against predators. We report that the S-layer of Caulobacter crescentus exhibits
calcium-mediated structural plasticity, switching irreversibly between an
amorphous aggregate state and the crystalline state. This finding invalidates the
common assumption that S-layers serve only as static wall-like structures. In
vitro, the Caulobacter S-layer protein, RsaA, enters the aggregate state at
physiological temperatures and low divalent calcium ion concentrations. At higher
concentrations, calcium ions stabilize monomeric RsaA, which can then transition
to the two-dimensional crystalline state. Caulobacter requires micromolar
concentrations of calcium for normal growth and development. Without an S-layer,
Caulobacter is even more sensitive to changes in environmental calcium
concentration. Therefore, this structurally dynamic S-layer responds to
environmental conditions as an ion sensor and protects Caulobacter from calcium
deficiency stress, a unique mechanism of bacterial adaptation. These findings
provide a biochemical and physiological basis for RsaA's calcium-binding
behavior, which extends far beyond calcium's commonly accepted role in aiding S
layer biogenesis or oligomerization and demonstrates a connection to cellular
fitness.
PMID- 28494956
TI - Resolution of Submillisecond Kinetics of Multiple Reaction Pathways for Lactate
Dehydrogenase.
AB - Enzymes are known to exhibit conformational flexibility. An important consequence
of this flexibility is that the same enzyme reaction can occur via multiple
reaction pathways on a reaction landscape. A model enzyme for the study of
reaction landscapes is lactate dehydrogenase. We have previously used temperature
jump (T-jump) methods to demonstrate that the reaction landscape of lactate
dehydrogenase branches at multiple points creating pathways with varied
reactivity. A limitation of this previous work is that the T-jump method makes
only small perturbations to equilibrium and may not report conclusively on all
steps in a reaction. Therefore, interpreting T-jump results of lactate
dehydrogenase kinetics has required extensive computational modeling work. Rapid
mixing methods offer a complementary approach that can access large perturbations
from equilibrium; however, traditional enzyme mixing methods like stopped-flow do
not allow for the observation of fast protein dynamics. In this report, we apply
a microfluidic rapid mixing device with a mixing time of <100 MUs that allows us
to study these fast dynamics and the catalytic redox step of the enzyme reaction.
Additionally, we report UV absorbance and emission T-jump results with improved
signal-to-noise ratio at fast times. The combination of mixing and T-jump results
yields an unprecedented view of lactate dehydrogenase enzymology, confirming the
timescale of substrate-induced conformational change and presence of multiple
reaction pathways.
PMID- 28494957
TI - Antioxidant and Membrane Binding Properties of Serotonin Protect Lipids from
Oxidation.
AB - Serotonin (5-hydroxytryptamine, 5-HT) is a well-known neurotransmitter that is
involved in a growing number of functions in peripheral tissues. Recent studies
have shown nonpharmacological functions of 5-HT linked to its chemical
properties. Indeed, it was reported that 5-HT may, on the one hand, bind lipid
membranes and, on the other hand, protect red blood cells through a mechanism
independent of its specific receptors. To better understand these underevaluated
properties of 5-HT, we combined biochemical, biophysical, and molecular dynamics
simulations approaches to characterize, at the molecular level, the antioxidant
capacity of 5-HT and its interaction with lipid membranes. To do so, 5-HT was
added to red blood cells and lipid membranes bearing different degrees of
unsaturation. Our results demonstrate that 5-HT acts as a potent antioxidant and
binds with a superior affinity to lipids with unsaturation on both alkyl chains.
We show that 5-HT locates at the hydrophobic-hydrophilic interface, below the
glycerol group. This interfacial location is stabilized by hydrogen bonds between
the 5-HT hydroxyl group and lipid headgroups and allows 5-HT to intercept
reactive oxygen species, preventing membrane oxidation. Experimental and
molecular dynamics simulations using membrane enriched with oxidized lipids
converge to further reveal that 5-HT contributes to the termination of lipid
peroxidation by direct interaction with active groups of these lipids and could
also contribute to limit the production of new radicals. Taken together, our
results identify 5-HT as a potent inhibitor of lipid peroxidation and offer a
different perspective on the role of this pleiotropic molecule.
PMID- 28494959
TI - Mechanosensitive Conformation of Vinculin Regulates Its Binding to MAPK1.
AB - Extracellular matrix stiffness sensing by living cells is known to play a major
role in a variety of cell mechanobiological processes, such as migration and
differentiation. Various membrane and cytoplasmic proteins are involved in
transmitting and transducing environmental signals to biochemical cascades.
Protein kinases play a key role in regulating the activity of focal adhesion
proteins. Recently, an interaction between mitogen-activated protein kinase
(MAPK1) and vinculin was experimentally shown to mediate this process. Here, we
adopt a molecular modeling approach to further investigate this interaction and
its possible regulatory effects. Using a combination of data-driven flexible
docking and molecular dynamics simulations guided by previous experimental
studies, we predict the structure of the MAPK1-vinculin complex. Furthermore, by
comparing the association of MAPK1 with open versus closed vinculin, we
demonstrate that MAPK1 exhibits preferential binding toward the open conformation
of vinculin, suggesting that the MAPK1-vinculin interaction is conformationally
selective. Finally, we demonstrate that changes in the size of the D3-D4 cleft
provide a structural basis for the conformational selectivity of the interaction.
PMID- 28494958
TI - Integrated Analysis of Intracellular Dynamics of MenaINV Cancer Cells in a 3D
Matrix.
AB - The intracellular environment is composed of a filamentous network that exhibits
dynamic turnover of cytoskeletal components and internal force generation from
molecular motors. Particle tracking microrheology enables a means to probe the
internal mechanics and dynamics. Here, we develop an analytical model to capture
the basic features of the active intracellular mechanical environment, including
both thermal and motor-driven effects, and show consistency with a diverse range
of experimental microrheology data. We further perform microrheology experiments,
integrated with Brownian dynamics simulations of the active cytoskeleton, on
metastatic breast cancer cells embedded in a three-dimensional collagen matrix
with and without the presence of epidermal growth factor to probe the
intracellular mechanical response in a physiologically mimicking scenario. Our
results demonstrate that EGF stimulation can alter intracellular stiffness and
power output from molecular motor-driven fluctuations in cells overexpressing an
invasive isoform of the actin-associated protein Mena.
PMID- 28494960
TI - Laser-Activated Polymeric Microcapsules for Ultrasound Imaging and Therapy: In
Vitro Feasibility.
AB - Polymeric microcapsules with a light-absorbing dye incorporated in their shell
can generate vapor microbubbles that can be spatiotemporally controlled by pulsed
laser irradiation. These contrast agents of 6-8 MUm in diameter can circulate
through the vasculature, offering possibilities for ultrasound (molecular)
imaging and targeted therapies. Here, we study the impact of such vapor bubbles
on human endothelial cells in terms of cell poration and cell viability to
establish the imaging and therapeutic windows. Two capsule formulations were
used: the first one consisted of a high boiling point oil (hexadecane), whereas
the second was loaded with a low boiling point oil (perfluoropentane). Poration
probability was already 40% for the smallest bubbles that were formed (<7.5 MUm
diameter), and reached 100% for the larger bubbles. The hexadecane-loaded
capsules also produced bubbles while their shell remained intact. These
encapsulated bubbles could therefore be used for noninvasive ultrasound imaging
after laser activation without inducing any cell damage. The controlled and
localized cell destruction achieved by activation of both capsule formulations
may provide an innovative approach for specifically inducing cell death in vivo,
e.g., for cancer therapy.
PMID- 28494961
TI - Rolling Adhesion of Schizont Stage Malaria-Infected Red Blood Cells in Shear
Flow.
AB - To avoid clearance by the spleen, red blood cells infected with the human malaria
parasite Plasmodium falciparum (iRBCs) adhere to the vascular endothelium through
adhesive protrusions called "knobs" that the parasite induces on the surface of
the host cell. However, the detailed relation between the developing knob
structure and the resulting movement in shear flow is not known. Using flow
chamber experiments on endothelial monolayers and tracking of the parasite inside
the infected host cell, we find that trophozoites (intermediate-stage iRBCs) tend
to flip due to their biconcave shape, whereas schizonts (late-stage iRBCs) tend
to roll due to their almost spherical shape. We then use adhesive dynamics
simulations for spherical cells to predict the effects of knob density and
receptor multiplicity per knob on rolling adhesion of schizonts. We find that
rolling adhesion requires a homogeneous coverage of the cell surface by knobs and
that rolling adhesion becomes more stable and slower for higher knob density. Our
experimental data suggest that schizonts are at the border between transient and
stable rolling adhesion. They also allow us to establish an estimate for the
molecular parameters for schizont adhesion to the vascular endothelium and to
predict bond dynamics in the contact region.
PMID- 28494962
TI - Nuclear Positioning and Its Translational Dynamics Are Regulated by Cell
Geometry.
AB - The collective activity of several molecular motors and other active processes
generate large forces for directional motion within the cell, which is vital for
a multitude of cellular functions such as migration, division, contraction,
transport, and positioning of various organelles. These processes also generate a
background of fluctuating forces, which influence intracellular dynamics and
thereby create unique biophysical signatures, which are altered in many diseases.
In this study, we have used the nucleus as a probe particle to understand the
microrheological properties of altered intracellular environments by using
micropatterning to confine cells in two structurally and functionally extreme
geometries. We find that nuclear positional dynamics is sensitive to the
cytoskeletal organization by studying the effect of actin polymerization and
nuclear rigidity on the diffusive behavior of the nucleus. Taken together, our
results suggest that mapping nuclear positional dynamics provides important
insights into biophysical properties of the active cytoplasmic medium. These
biophysical signatures have the potential to be used as an ultrasensitive single
cell assay for early disease diagnostics.
PMID- 28494964
TI - Near-Membrane Refractometry Using Supercritical Angle Fluorescence.
AB - Total internal reflection fluorescence (TIRF) microscopy and its variants are key
technologies for visualizing the dynamics of single molecules or organelles in
live cells. Yet truly quantitative TIRF remains problematic. One unknown
hampering the interpretation of evanescent-wave excited fluorescence intensities
is the undetermined cell refractive index (RI). Here, we use a combination of
TIRF excitation and supercritical angle fluorescence emission detection to
directly measure the average RI in the "footprint" region of the cell during
image acquisition. Our RI measurement is based on the determination on a back
focal plane image of the critical angle separating evanescent and far-field
fluorescence emission components. We validate our method by imaging mouse
embryonic fibroblasts and BON cells. By targeting various dyes and fluorescent
protein chimeras to vesicles, the plasma membrane, as well as mitochondria and
the endoplasmic reticulum, we demonstrate local RI measurements with subcellular
resolution on a standard TIRF microscope, with a removable Bertrand lens as the
only modification. Our technique has important applications for imaging axial
vesicle dynamics and the mitochondrial energy state or detecting metabolically
more active cancer cells.
PMID- 28494963
TI - Design and Properties of Genetically Encoded Probes for Sensing Macromolecular
Crowding.
AB - Cells are highly crowded with proteins and polynucleotides. Any reaction that
depends on the available volume can be affected by macromolecular crowding, but
the effects of crowding in cells are complex and difficult to track. Here, we
present a set of Forster resonance energy transfer (FRET)-based crowding
sensitive probes and investigate the role of the linker design. We investigate
the sensors in vitro and in vivo and by molecular dynamics simulations. We find
that in vitro all the probes can be compressed by crowding, with a magnitude that
increases with the probe size, the crowder concentration, and the crowder size.
We capture the role of the linker in a heuristic scaling model, and we find that
compression is a function of size of the probe and volume fraction of the
crowder. The FRET changes observed in Escherichia coli are more complicated,
where FRET-increases and scaling behavior are observed solely with probes that
contain the helices in the linker. The probe with the highest sensitivity to
crowding in vivo yields the same macromolecular volume fractions as previously
obtained from cell dry weight. The collection of new probes provides more
detailed readouts on the macromolecular crowding than a single sensor.
PMID- 28494965
TI - Multiscale Determinants of Delayed Afterdepolarization Amplitude in Cardiac
Tissue.
AB - Spontaneous calcium (Ca) waves in cardiac myocytes underlie delayed
afterdepolarizations (DADs) that trigger cardiac arrhythmias. How these
subcellular/cellular events overcome source-sink factors in cardiac tissue to
generate DADs of sufficient amplitude to trigger action potentials is not fully
understood. Here, we evaluate quantitatively how factors at the subcellular scale
(number of Ca wave initiation sites), cellular scale (sarcoplasmic reticulum (SR)
Ca load), and tissue scale (synchrony of Ca release in populations of myocytes)
determine DAD features in cardiac tissue using a combined experimental and
computational modeling approach. Isolated patch-clamped rabbit ventricular
myocytes loaded with Fluo-4 to image intracellular Ca were rapidly paced during
exposure to elevated extracellular Ca (2.7 mmol/L) and isoproterenol (0.25
MUmol/L) to induce diastolic Ca waves and subthreshold DADs. As the number of
paced beats increased from 1 to 5, SR Ca content (assessed with caffeine pulses)
increased, the number of Ca wave initiation sites increased, integrated Ca
transients and DADs became larger and shorter in duration, and the latency period
to the onset of Ca waves shortened with reduced variance. In silico analysis
using a computer model of ventricular tissue incorporating these experimental
measurements revealed that whereas all of these factors promoted larger DADs with
higher probability of generating triggered activity, the latency period variance
and SR Ca load had the greatest influences. Therefore, incorporating quantitative
experimental data into tissue level simulations reveals that increased
intracellular Ca promotes DAD-mediated triggered activity in tissue predominantly
by increasing both the synchrony (decreasing latency variance) of Ca waves in
nearby myocytes and SR Ca load, whereas the number of Ca wave initiation sites
per myocyte is less important.
PMID- 28494966
TI - Mechanotransduction Dynamics at the Cell-Matrix Interface.
AB - The ability of cells to sense and respond to mechanical cues from the surrounding
environment has been implicated as a key regulator of cell differentiation,
migration, and proliferation. The extracellular matrix (ECM) is an oft-overlooked
component of the interface between cells and their surroundings. Cells assemble
soluble ECM proteins into insoluble fibrils with unique mechanical properties
that can alter the mechanical cues a cell receives. In this study, we construct a
model that predicts the dynamics of cellular traction force generation and
subsequent assembly of fibrils of the ECM protein fibronectin (FN). FN fibrils
are the primary component in primordial ECM and, as such, FN assembly is a
critical component in the cellular mechanical response. The model consists of a
network of Hookean springs, each representing an extensible domain within an
assembling FN fibril. As actomyosin forces stretch the spring network,
simulations predict the resulting traction force and FN fibril formation. The
model accurately predicts FN fibril morphometry and demonstrates a mechanism by
which FN fibril assembly regulates traction force dynamics in response to
mechanical stimuli and varying surrounding substrate stiffness.
PMID- 28494967
TI - Visualizing Calcium Flux in Freely Moving Nematode Embryos.
AB - The lack of physiological recordings from Caenorhabditis elegans embryos stands
in stark contrast to the comprehensive anatomical and gene expression datasets
already available. Using light-sheet fluorescence microscopy to address the
challenges associated with functional imaging at this developmental stage, we
recorded calcium dynamics in muscles and neurons and developed analysis
strategies to relate activity and movement. In muscles, we found that the
initiation of twitching was associated with a spreading calcium wave in a dorsal
muscle bundle. Correlated activity in muscle bundles was linked with early
twitching and eventual coordinated movement. To identify neuronal correlates of
behavior, we monitored brainwide activity with subcellular resolution and
identified a particularly active cell associated with muscle contractions.
Finally, imaging neurons of a well-defined adult motor circuit, we found that
reversals in the eggshell correlated with calcium transients in AVA interneurons.
PMID- 28494968
TI - Bistability and Nonmonotonic Induction of the lac Operon in the Natural Lactose
Uptake System.
AB - The Escherichia coli lac operon is regulated by a positive feedback loop whose
potential to generate an all-or-none response in single cells has been a paradigm
for bistable gene expression. However, so far bistable lac induction has only
been observed using gratuitous inducers, raising the question about the
biological relevance of bistable lac induction in the natural setting with
lactose as the inducer. In fact, the existing experimental evidence points to a
graded rather than an all-or-none response in the natural lactose uptake system.
In contrast, predictions based on computational models of the lactose uptake
pathway remain controversial. Although some argue in favor of bistability, others
argue against it. Here, we reinvestigate lac operon expression in single cells
using a combined experimental/modeling approach. To this end, we parameterize a
well-supported mathematical model using transient measurements of LacZ activity
upon induction with different amounts of lactose. The resulting model predicts a
monostable induction curve for the wild-type system, but indicates that
overexpression of the LacI repressor would drive the system into the bistable
regime. Both predictions were confirmed experimentally supporting the view that
the wild-type lac induction circuit generates a graded response rather than
bistability. More interestingly, we find that the lac induction curve exhibits a
pronounced maximum at intermediate lactose concentrations. Supported by our data,
a model-based analysis suggests that the nonmonotonic response results from
saturation of the LacI repressor at low inducer concentrations and dilution of
Lac enzymes due to an increased growth rate beyond the saturation point. We
speculate that the observed maximum in the lac expression level helps to save
cellular resources by limiting Lac enzyme expression at high inducer
concentrations.
PMID- 28494969
TI - Rate-Dependent Role of IKur in Human Atrial Repolarization and Atrial
Fibrillation Maintenance.
AB - The atrial-specific ultrarapid delayed rectifier K+ current (IKur) inactivates
slowly but completely at depolarized voltages. The consequences for IKur rate
dependence have not been analyzed in detail and currently available mathematical
action-potential (AP) models do not take into account experimentally observed
IKur inactivation dynamics. Here, we developed an updated formulation of IKur
inactivation that accurately reproduces time-, voltage-, and frequency-dependent
inactivation. We then modified the human atrial cardiomyocyte Courtemanche AP
model to incorporate realistic IKur inactivation properties. Despite markedly
different inactivation dynamics, there was no difference in AP parameters across
a wide range of stimulation frequencies between the original and updated models.
Using the updated model, we showed that, under physiological stimulation
conditions, IKur does not inactivate significantly even at high atrial rates
because the transmembrane potential spends little time at voltages associated
with inactivation. Thus, channel dynamics are determined principally by
activation kinetics. IKur magnitude decreases at higher rates because of AP
changes that reduce IKur activation. Nevertheless, the relative contribution of
IKur to AP repolarization increases at higher frequencies because of reduced
activation of the rapid delayed-rectifier current IKr. Consequently, IKur block
produces dose-dependent termination of simulated atrial fibrillation (AF) in the
absence of AF-induced electrical remodeling. The inclusion of AF-related ionic
remodeling stabilizes simulated AF and greatly reduces the predicted
antiarrhythmic efficacy of IKur block. Our results explain a range of
experimental observations, including recently reported positive rate-dependent
IKur-blocking effects on human atrial APs, and provide insights relevant to the
potential value of IKur as an antiarrhythmic target for the treatment of AF.
PMID- 28494971
TI - Introduction to Biophysics Week: What is Biophysics?
PMID- 28494970
TI - Image-Based Measurement of H2O2 Reaction-Diffusion in Wounded Zebrafish Larvae.
AB - Epithelial injury induces rapid recruitment of antimicrobial leukocytes to the
wound site. In zebrafish larvae, activation of the epithelial NADPH oxidase Duox
at the wound margin is required early during this response. Before injury,
leukocytes are near the vascular region, that is, ~100-300 MUm away from the
injury site. How Duox establishes long-range signaling to leukocytes is unclear.
We conceived that extracellular hydrogen peroxide (H2O2) generated by Duox
diffuses through the tissue to directly regulate chemotactic signaling in these
cells. But before it can oxidize cellular proteins, H2O2 must get past the
antioxidant barriers that protect the cellular proteome. To test whether, or on
which length scales this occurs during physiological wound signaling, we
developed a computational method based on reaction-diffusion principles that
infers H2O2 degradation rates from intravital H2O2-biosensor imaging data. Our
results indicate that at high tissue H2O2 levels the peroxiredoxin-thioredoxin
antioxidant chain becomes overwhelmed, and H2O2 degradation stalls or ceases.
Although the wound H2O2 gradient reaches deep into the tissue, it likely
overcomes antioxidant barriers only within ~30 MUm of the wound margin. Thus,
Duox-mediated long-range signaling may require other spatial relay mechanisms
besides extracellular H2O2 diffusion.
PMID- 28494973
TI - Retention in high-performance liquid chromatography at -196 degrees C.
AB - Recently, we have developed ultralow-temperature high-performance liquid
chromatography (HPLC) at -196 degrees C using liquid nitrogen-based mobile
phases. In this study, a retention model for ultralow-temperature HPLC, in which
adsorption exchange and "pseudo partition" modes are combined, is proposed to
describe the effect of the mobile phase composition on the retention of analytes.
The experimental results agreed well with the equation of the proposed model. It
was revealed that, in the low and high additive concentration regions, adsorption
exchange and pseudo partition retention, respectively, dominate the analyte
retention. The difference in the retention behavior between bare-silica and
octadecylsilyl-modified silica (ODS) columns was also studied. Retention of
alkanes in the ODS column was greater than that in the bare-silica one. Addition
of both ethane and ethylene to the mobile phase in the ODS column afforded the
elution of propylene, which was not eluted with the bare-silica column at -196
degrees C.
PMID- 28494972
TI - Synaptic Impairment in Alzheimer's Disease: A Dysregulated Symphony.
AB - Alzheimer's disease (AD) is characterized by memory loss, cognitive decline, and
devastating neurodegeneration, not only as a result of the extracellular
accumulation of beta-amyloid peptide (Abeta) and intracellular accumulation of
tau, but also as a consequence of the dysfunction and loss of synapses. Although
significant advances have been made in our understanding of the relationship of
the pathological role of Abeta and tau in synapse dysfunction, several questions
remain as to how Abeta and tau interdependently cause impairments in synaptic
function in AD. Overall, more insight into these questions should enable
researchers in this field to develop novel therapeutic targets to mitigate or
delay the cognitive deficits associated with this devastating disease.
PMID- 28494975
TI - Navigating Choices Among a Sea of Comorbidities.
PMID- 28494974
TI - Multiple Comorbidities and Response to Cardiac Resynchronization Therapy: MADIT
CRT Long-Term Follow-Up.
AB - BACKGROUND: Data regarding cardiac resynchronization therapy (CRT) in patients
with multiple comorbidities are limited. OBJECTIVES: This study evaluated the
association of multiple comorbidities with the benefits of CRT over implantable
cardioverter-defibrillator (ICD) alone. METHODS: We examined 1,214 MADIT-CRT
(Multicenter Automatic Defibrillator Implantation Trial with Cardiac
Resynchronization Therapy) study patients with left bundle branch block (LBBB)
and 0, 1, 2, or >=3 comorbidities, including renal dysfunction, hypertension
(HTN), diabetes, coronary artery disease, history of atrial arrhythmias, history
of ventricular arrhythmias, current smoking, and cerebrovascular accident. In an
adjusted analysis, we analyzed risk of heart failure (HF) events or death by
comorbidity group in all patients and in patients with CRT with defibrillator
(CRT-D) versus ICD. Then we examined percent change in left ventricular (LV) end
diastolic volume, LV end-systolic volume, LV ejection fraction, left atrial
volume, and LV dyssynchrony at 1-year in CRT-D patients by comorbidity group.
RESULTS: There was an inverse relationship between comorbidity burden and
improvements in LV end-systolic volume, LV end-diastolic volume, left ventricular
ejection fraction, left atrial volume, and LV dyssynchrony. In an adjusted model,
there was an increasing risk of death or nonfatal HF events with increasing
comorbidity burden regardless of treatment group (p < 0.001). During a mean
follow-up of 4.65 years, there was no interaction with respect to comorbidity
burden and the benefit of CRT-D versus ICD only for death or nonfatal HF events
(interaction p = 0.943). In the groups with greatest comorbidity burden (2 and
>=3), the absolute risk reduction associated with CRT-D over ICD alone appeared
greater than that seen for groups with less comorbidity burden (0 and 1).
CONCLUSIONS: During long-term follow-up of MADIT-CRT study patients with LBBB
randomized to CRT-D, there were differences in HF or death risk and in the degree
of reverse remodeling among comorbidity groups. However, the burden of
comorbidity does not appear to compromise the clinical benefits of CRT-D compared
with ICD alone.
PMID- 28494977
TI - Aortic Stenosis Is Still Very Tricky, Especially When it Is Moderate.
PMID- 28494976
TI - Prognostic Implications of Moderate Aortic Stenosis in Patients With Left
Ventricular Systolic Dysfunction.
AB - BACKGROUND: Left ventricular (LV) systolic dysfunction and moderate aortic
stenosis (AS) are more frequent with advancing age and often coexist. Afterload
reduction is the mainstay of pharmacological treatment of heart failure (HF).
Aortic valve replacement (AVR) is only formally indicated for symptomatic severe
AS. OBJECTIVES: This study sought to determine the clinical outcome of patients
with concomitant moderate AS and LV systolic dysfunction. METHODS:
Echocardiographic and clinical data of patients with moderate AS and LV systolic
dysfunction between 2010 and 2015 from 4 large academic institutions were
retrospectively analyzed. Moderate AS was defined as aortic valve area between
1.0 and 1.5 cm2 and LV systolic dysfunction defined as LV ejection fraction <50%.
The primary endpoint was a composite of all-cause death, AVR, and HF
hospitalization. RESULTS: A total of 305 patients (mean age 73 +/- 11 years; 75%
male) were included. The majority were symptomatic at the time of index
echocardiogram (New York Heart Association [NYHA] functional class II: 42%; NYHA
functional class III: 28%; and NYHA functional class IV: 4%). Ischemic heart
disease was present in 72% of patients. At 4-year follow-up, the primary
composite endpoint occurred in 61%. The main predictors for the primary endpoint
were male sex (p = 0.022), NYHA functional class III or IV (p < 0.001), and peak
aortic jet velocity (p < 0.001). The rate of the composite of all-cause death or
HF hospitalization was 48%, rate of all-cause death was 36%, and rate of HF
hospitalization was 27%. AVR occurred in 24% of patients. CONCLUSIONS: Patients
with concomitant moderate AS and LV systolic dysfunction are at high risk for
clinical events. Further studies are needed to determine if earlier AVR in these
patients might improve clinical outcome.
PMID- 28494978
TI - Post-Operative Chylothorax in Patients With Congenital Heart Disease.
AB - BACKGROUND: Post-operative chylothorax in patients with congenital heart disease
is a challenging problem with substantial morbidity and mortality. Currently, the
etiology of chylothorax is poorly understood and treatment options are limited.
OBJECTIVES: This study aimed to report lymphatic imaging findings, determine the
mechanism of chylothorax after cardiac surgery, and analyze the outcomes of
lymphatic embolization. METHODS: We conducted a retrospective review of 25
patients with congenital heart disease and post-operative chylothorax who
presented for lymphatic imaging and intervention between July 2012 and August
2016. RESULTS: Based on dynamic contrast-enhanced magnetic resonance
lymphangiography and intranodal lymphangiography, we identified 3 distinct
etiologies of chylothorax: 2 patients (8%) with traumatic leak from a thoracic
duct (TD) branch, 14 patients (56%) with pulmonary lymphatic perfusion syndrome
(PLPS), and 9 patients (36%) with central lymphatic flow disorder (CLFD), the
latter defined as abnormal central lymphatic flow, effusions in more than 1
compartment, and dermal backflow. Patients with traumatic leak and PLPS were
combined into 1 group of 16 patients without CLFD, of whom 14 (88%) had an intact
TD. Sixteen patients underwent lymphatic intervention, including complete TD
embolization. All 16 patients had resolution of chylothorax, with a median of 7.5
days from intervention to chest tube removal and 15 days from intervention to
discharge. The 9 patients with CLFD were considered a separate group, of whom 3
(33%) had an intact TD. Seven patients underwent lymphatic intervention but none
survived. CONCLUSIONS: Most patients in this study had nontraumatic chylothorax
and dynamic contrast-enhanced magnetic resonance lymphangiography was essential
to determine etiology. Lymphatic embolization was successful in patients with
traumatic leak and PLPS and, thus, should be considered first-line treatment.
Interventions in patients with CLFD were not successful to resolve chylothorax
and alternate approaches need to be developed.
PMID- 28494979
TI - Lymphodynamics in Congenital Heart Disease: The Forgotten Circulation.
PMID- 28494982
TI - Advocacy for Health Care: All Hands on Deck!
PMID- 28494983
TI - Chest Pain Unit Network in Germany: Its Effect on Patients With Acute Coronary
Syndromes.
PMID- 28494981
TI - Using Predicted Cardiovascular Disease Risk in Conjunction With Blood Pressure to
Guide Antihypertensive Medication Treatment.
AB - Using cardiovascular disease (CVD) risk instead of or in addition to blood
pressure (BP) to guide antihypertensive treatment is an active area of research.
The purpose of this review is to provide an overview of studies that could inform
this treatment paradigm. We review data from randomized trials on relative and
absolute CVD risk reduction that can occur when antihypertensive treatment is
guided by CVD risk. We also review population-level data on using CVD risk in
conjunction with BP to guide antihypertensive treatment, the broad distribution
in CVD risk for people with similar BP levels, and the use of CVD risk for
guiding antihypertensive treatment among subgroups including older adults, young
adults, and those with diabetes mellitus or chronic kidney disease. In addition,
we review potential challenges in implementing antihypertensive treatment
recommendations that incorporate CVD risk. In closing, we provide recommendations
for using CVD risk in combination with BP to guide antihypertensive treatment.
PMID- 28494980
TI - Extracorporeal Ultrafiltration for Fluid Overload in Heart Failure: Current
Status and Prospects for Further Research.
AB - More than 1 million heart failure hospitalizations occur annually, and congestion
is the predominant cause. Rehospitalizations for recurrent congestion portend
poor outcomes independently of age and renal function. Persistent congestion
trumps serum creatinine increases in predicting adverse heart failure outcomes.
No decongestive pharmacological therapy has reduced these harmful consequences.
Simplified ultrafiltration devices permit fluid removal in lower-acuity hospital
settings, but with conflicting results regarding safety and efficacy.
Ultrafiltration performed at fixed rates after onset of therapy-induced increased
serum creatinine was not superior to standard care and resulted in more
complications. In contrast, compared with diuretic agents, some data suggest that
adjustment of ultrafiltration rates to patients' vital signs and renal function
may be associated with more effective decongestion and fewer heart failure
events. Essential aspects of ultrafiltration remain poorly defined. Further
research is urgently needed, given the burden of congestion and data suggesting
sustained benefits of early and adjustable ultrafiltration.
PMID- 28494984
TI - Global Cardiovascular Health: A Role for the Interventionalist.
PMID- 28494985
TI - Role of Acquired Cardiovascular Disease in Tetralogy of Fallot Patients >50 Years
of Age.
PMID- 28494986
TI - Truncating Variants in Titin Independently Predict Early Arrhythmias in Patients
With Dilated Cardiomyopathy.
PMID- 28494987
TI - Neurocognitive Risk With PCSK9 Inhibitors: Need for More Robust Evidence.
PMID- 28494988
TI - The Enigma of Left Ventricular Hypertrabeculation: Knowledge About Pregnancies,
Sports, and Neuromuscular Disorders Is Needed.
PMID- 28494989
TI - Reply: The Enigma of Left Ventricular Non-Compaction.
PMID- 28494990
TI - Reply: Mortality and Acute Kidney Injury in Asians With Atrial Fibrillation
Treated With Dabigatran or Warfarin.
PMID- 28494992
TI - Correction.
PMID- 28494991
TI - Mortality and Acute Kidney Injury in Asians With Atrial Fibrillation Treated With
Dabigatran or Warfarin.
PMID- 28494993
TI - Robust activation detection methods for real-time and offline fMRI analysis.
AB - We propose two contributions with novel approaches to fMRI activation analysis.
The first is to apply confidence intervals to locate activations in real-time,
and second is a new metric based on robust regression of fMRI signals. These
contributions are implemented in our four proposed methods; Instantaneous
Activation Method (IAM), Instantaneous Activation Method with Past Blocks (IAMP)
for real-time analysis, Task Robust Regression Distance Method (TRRD) for the new
metric with robust regression and Instantaneous Robust Regression Distance Method
(IRRD) for both contributions. For comparison, a statistical offline method
called Task Activation Method (TAM) and a correlation analysis method are also
implemented. The methods are initially evaluated with synthetic data generated
using two different approaches; first using varying hemodynamic response function
signals to simulate a wide range of stimuli responses, along with a Gaussian
white noise, and second using no activity state data of a real fMRI experiment,
which removes the need to generate noise. The methods are also tested with real
fMRI experiments and compared with the results obtained by the widely used SPM
tool. The results show that instantaneous methods reveal activations that are
lost statistically in an offline analysis. They also reveal further improvements
by robust fitting application, which minimizes the outlier effect. TRRD has an
area under the ROC curve of 0,7127 for very noisy synthetic images, is reaching
up to 0,9608 as the noise decreases, while the instantaneous score is in the
range of 0,6124 to 0,8019 in the same noise levels.
PMID- 28494994
TI - Predicting return visits to the emergency department for pediatric patients:
Applying supervised learning techniques to the Taiwan National Health Insurance
Research Database.
AB - BACKGROUND AND OBJECTIVE: Return visits (RVs) to the emergency department (ED)
consume medical resources and may represent a patient safety issue. The
occurrence of unexpected RVs is considered a performance indicator for ED care
quality. Because children are susceptible to medical errors and utilize
considerable ED resources, knowing the factors that affect RVs in pediatric
patients helps improve the quality of pediatric emergency care. METHODS: We
collected data on visits made by patients aged <=18years to EDs from the National
Health Insurance Research Database. The outcome of interest was a RV within 3days
of the initial visit. Potential factors were categorized into demographics,
medical history, features of ED visits, physician characteristics, hospital
characteristics, and treatment-seeking behavior. A multivariate logistic
regression was used to identify independent predictors of RVs. We compared the
performance of various data mining techniques, including Naive Bayes,
classification and regression tree (CART), random forest, and logistic
regression, in predicting RVs. Finally, we developed a decision tree to stratify
the risk of RVs. RESULTS: Of 125,940 visits, 6,282 (5.0%) were followed by a RV
within 3 days. Predictors of RVs included younger age, higher acuity, intravenous
fluid, more examination types, complete blood count, consultation, lower hospital
level, hospitalization within one week before the initial visit, frequent ED
visits in the past one year, and visits made in Spring or on Saturdays. Patients
with allergic diseases and those underwent ultrasound examination were less
likely to return. Decision tree models performed better in predicting RVs in
terms of area under curve. The decision tree constructed using the CART technique
showed that the number of ED visits in the past one year, diagnosis category,
testing of complete blood count, and age were important discriminators of risk of
RVs. CONCLUSIONS: We identified several factors which are associated with RVs to
the ED in pediatric patients. The knowledge of these factors may help assess risk
of RVs in the ED and guide physicians to reevaluate and provide interventions to
children belonging to the high risk groups before ED discharge.
PMID- 28494995
TI - High-accuracy detection of airway obstruction in asthma using machine learning
algorithms and forced oscillation measurements.
AB - BACKGROUND AND OBJECTIVES: The main pathologic feature of asthma is episodic
airway obstruction. This is usually detected by spirometry and body
plethysmography. These tests, however, require a high degree of collaboration and
maximal effort on the part of the patient. There is agreement in the literature
that there is a demand of research into new technologies to improve non-invasive
testing of lung function. The purpose of this study was to develop automatic
classifiers to simplify the clinical use and to increase the accuracy of the
forced oscillation technique (FOT) in the diagnosis of airway obstruction in
patients with asthma. METHODS: The data consisted of FOT parameters obtained from
75 volunteers (39 with obstruction and 36 without). Different supervised machine
learning (ML) techniques were investigated, including k-nearest neighbors (KNN),
random forest (RF), AdaBoost with decision trees (ADAB) and feature-based
dissimilarity space classifier (FDSC). RESULTS: The first part of this study
showed that the best FOT parameter was the resonance frequency (AUC = 0.81),
which indicates moderate accuracy (0.70-0.90). In the second part of this study,
the use of the cited ML techniques was investigated. All the classifiers improved
the diagnostic accuracy. Notably, ADAB and KNN were very close to achieving high
accuracy (AUC = 0.88 and 0.89, respectively). Experiments including the cross
products of the FOT parameters showed that all the classifiers improved the
diagnosis accuracy and KNN was able to reach a higher accuracy range (AUC =
0.91). CONCLUSIONS: Machine learning classifiers can help in the diagnosis of
airway obstruction in asthma patients, and they can assist clinicians in airway
obstruction identification.
PMID- 28494996
TI - Prediction of labor onset type: Spontaneous vs induced; role of
electrohysterography?
AB - BACKGROUND AND OBJECTIVE: Induction of labor (IOL) is a medical procedure used to
initiate uterine contractions to achieve delivery. IOL entails medical risks and
has a significant impact on both the mother's and newborn's well-being. The
assistance provided by an automatic system to help distinguish patients that will
achieve labor spontaneously from those that will need late-term IOL would help
clinicians and mothers to take an informed decision about prolonging pregnancy.
With this aim, we developed and evaluated predictive models using not only
traditional obstetrical data but also electrophysiological parameters derived
from the electrohysterogram (EHG). METHODS: EHG recordings were made on singleton
term pregnancies. A set of 10 temporal and spectral parameters was calculated to
characterize EHG bursts and a further set of 6 common obstetrical parameters was
also considered in the predictive models design. Different models were
implemented based on single layer Support Vector Machines (SVM) and with
aggregation of majority voting of SVM (double layer), to distinguish between the
two groups: term spontaneous labor (<=41 weeks of gestation) and IOL late-term
labor. The areas under the curve (AUC) of the models were compared. RESULTS: The
obstetrical and EHG parameters of the two groups did not show statistically
significant differences. The best results of non-contextualized single input
parameter SVM models were achieved by the Bishop Score (AUC= 0.65) and GA at
recording time (AUC= 0.68) obstetrical parameters. The EHG parameter median
frequency, when contextualized with the two obstetrical parameters improved these
results, reaching AUC= 0.76. Multiple input SVM obtained AUC= 0.70 for all EHG
parameters. Aggregation of majority voting of SVM models using contextualized EHG
parameters achieved the best result AUC= 0.93. CONCLUSIONS: Measuring the
electrophysiological uterine condition by means of electrohysterographic
recordings yielded a promising clinical decision support system for
distinguishing patients that will spontaneously achieve active labor before the
end of full term from those who will require late term IOL. The importance of
considering these EHG measurements in the patient's individual context was also
shown by combining EHG parameters with obstetrical parameters. Clinicians
considering elective labor induction would benefit from this technique.
PMID- 28494997
TI - Multiple model predictive control for optimal drug administration of mixed
immunotherapy and chemotherapy of tumours.
AB - BACKGROUND: Mixed immunotherapy and chemotherapy of tumours is one of the most
efficient ways to improve cancer treatment strategies. However, it is important
to 'design' an effective treatment programme which can optimize the ways of
combining immunotherapy and chemotherapy to diminish their imminent side effects.
Control engineering techniques could be used for this. METHODS: The method of
multiple model predictive controller (MMPC) is applied to the modified Stepanova
model to induce the best combination of drugs scheduling under a better health
criteria profile. The proposed MMPC is a feedback scheme that can perform global
optimization for both tumour volume and immune competent cell density by
performing multiple constraints. RESULTS: Although current studies usually assume
that immunotherapy has no side effect, this paper presents a new method of mixed
drug administration by employing MMPC, which implements several constraints for
chemotherapy and immunotherapy by considering both drug toxicity and autoimmune.
With designed controller we need maximum 57% and 28% of full dosage of drugs for
chemotherapy and immunotherapy in some instances, respectively. Therefore,
through the proposed controller less dosage of drugs are needed, which contribute
to suitable results with a perceptible reduction in medicine side effects.
CONCLUSION: It is observed that in the presence of MMPC, the amount of required
drugs is minimized, while the tumour volume is reduced. The efficiency of the
presented method has been illustrated through simulations, as the system from an
initial condition in the malignant region of the state space (macroscopic tumour
volume) transfers into the benign region (microscopic tumour volume) in which the
immune system can control tumour growth.
PMID- 28494998
TI - A novel method for planning liver resections using deformable Bezier surfaces and
distance maps.
AB - BACKGROUND AND OBJECTIVE: For more than a decade, computer-assisted surgical
systems have been helping surgeons to plan liver resections. The most widespread
strategies to plan liver resections are: drawing traces in individual 2D slices,
and using a 3D deformable plane. In this work, we propose a novel method which
requires low level of user interaction while keeping high flexibility to specify
resections. METHODS: Our method is based on the use of Bezier surfaces, which can
be deformed using a grid of control points, and distance maps as a base to
compute and visualize resection margins (indicators of safety) in real-time.
Projection of resections in 2D slices, as well as computation of resection volume
statistics are also detailed. RESULTS: The method was evaluated and compared with
state-of-the-art methods by a group of surgeons (n=5, 5-31 years of experience).
Our results show that theproposed method presents planning times as low as state
of-the-art methods (174 s median time) with high reproducibility of results in
terms of resected volume. In addition, our method not only leads to smooth
virtual resections easier to perform surgically compared to other state-of-the
art methods, but also shows superior preservation of resection margins.
CONCLUSIONS: Our method provides clinicians with a robust and easy-to-use method
for planning liver resections with high reproducibility, smoothness of resection
and preservation of resection margin. Our results indicate the ability of the
method to represent any type of resection and being integrated in real clinical
work-flows.
PMID- 28494999
TI - Modeling and control of operator functional state in a unified framework of fuzzy
inference petri nets.
AB - BACKGROUND AND OBJECTIVE: In human-machine (HM) hybrid control systems, human
operator and machine cooperate to achieve the control objectives. To enhance the
overall HM system performance, the discrete manual control task-load by the
operator must be dynamically allocated in accordance with continuous-time
fluctuation of psychophysiological functional status of the operator, so-called
operator functional state (OFS). The behavior of the HM system is hybrid in
nature due to the co-existence of discrete task-load (control) variable and
continuous operator performance (system output) variable. METHODS: Petri net is
an effective tool for modeling discrete event systems, but for hybrid system
involving discrete dynamics, generally Petri net model has to be extended.
Instead of using different tools to represent continuous and discrete components
of a hybrid system, this paper proposed a method of fuzzy inference Petri nets
(FIPN) to represent the HM hybrid system comprising a Mamdani-type fuzzy model of
OFS and a logical switching controller in a unified framework, in which the task
load level is dynamically reallocated between the operator and machine based on
the model-predicted OFS. Furthermore, this paper used a multi-model approach to
predict the operator performance based on three electroencephalographic (EEG)
input variables (features) via the Wang-Mendel (WM) fuzzy modeling method. The
membership function parameters of fuzzy OFS model for each experimental
participant were optimized using artificial bee colony (ABC) evolutionary
algorithm. Three performance indices, RMSE, MRE, and EPR, were computed to
evaluate the overall modeling accuracy. RESULTS: Experiment data from six
participants are analyzed. The results show that the proposed method (FIPN with
adaptive task allocation) yields lower breakdown rate (from 14.8% to 3.27%) and
higher human performance (from 90.30% to 91.99%). CONCLUSION: The simulation
results of the FIPN-based adaptive HM (AHM) system on six experimental
participants demonstrate that the FIPN framework provides an effective way to
model and regulate/optimize the OFS in HM hybrid systems composed of continuous
time OFS model and discrete-event switching controller.
PMID- 28495000
TI - Prognostic value of tumor volume for patients with advanced lung cancer treated
with chemotherapy.
AB - BACKGROUND AND OBJECTIVE: We aim to develop a reference system utilizing computed
tomography to calculate changes in tumor volume of lung cancer patients after
chemotherapy to assist physicians in clinical treatment and evaluation. METHODS:
Image processing techniques were used to analyze the computed tomography of lung
cancer, locate the tumor, and calculate the tumor volume. The medical indicator
was then evaluated and analyzed. We examined the correlation between reduced
tumor volume and survival duration of 88 patients after chemotherapy at Tri
Service General Hospital, Taiwan. The innovative survival prediction index was
obtained by four statistical methods: receiver operating characteristic curve,
Youden index, Kaplan-Meier method, and log rank test. RESULTS: From the image
processing techniques, tumor volume from each patient were obtained within an
average of 7.25 seconds. The proposed method was shown to achieve rapid
positioning of lung tumors and volume reconstruction with an estimation error of
1.92% when calibrated with an irregularly shaped stone. In medical indicator
evaluation and analysis, the area below the receiver operating characteristic
curve is greater than 0.8, indicating good predictability of the medical index
used herein. The Youden index spotted the best cut-off point of volume, and the
correlation between the volume's cut-off point and survival time was confirmed
again by Kaplan-Meier and log rank test. The p-values were all less than 0.05,
presenting a high degree of correlation between the two, indicating that this
medical indicator is highly reliable. CONCLUSIONS: The proposed techniques can
automatically find the location of tumors in the lung, reconstruct the volume,
and calculate changes in volume before and after treatment, thus obtaining an
innovative survival prediction index. This will help facilitate early and
accurate predictions of disease outcomes during the course of therapy, and
categorize patient stratification into risk groups for more efficient therapies.
PMID- 28495002
TI - A hybrid energy model for region based curve evolution - Application to CTA
coronary segmentation.
AB - BACKGROUND AND OBJECTIVE: State-of-the-art medical imaging techniques have
enabled non-invasive imaging of the internal organs. However, high volumes of
imaging data make manual interpretation and delineation of abnormalities
cumbersome for clinicians. These challenges have driven intensive research into
efficient medical image segmentation. In this work, we propose a hybrid region
based energy formulation for effective segmentation in computed tomography
angiography (CTA) imagery. METHODS: The proposed hybrid energy couples an
intensity-based local term with an efficient discontinuity-based global model of
the image for optimal segmentation. The segmentation is achieved using a level
set formulation due to the computational robustness. After validating the
statistical significance of the hybrid energy, we applied the proposed model to
solve an important clinical problem of 3D coronary segmentation. An improved seed
detection method is used to initialize the level set evolution. Moreover, we
employed an auto-correction feature that captures the emerging peripheries during
the curve evolution for completeness of the coronary tree. RESULTS: We evaluated
the segmentation accuracy of the proposed energy model against the existing
techniques in two stages. Qualitative and quantitative results demonstrate the
effectiveness of the proposed framework with a consistent mean sensitivity and
specificity measures of 80% across the CTA data. Moreover, a high degree of
agreement with respect to the inter-observer differences justifies the
generalization of the proposed method. CONCLUSIONS: The proposed method is
effective to segment the coronary tree from the CTA volume based on hybrid image
based energy, which can improve the clinicians ability to detect arterial
abnormalities.
PMID- 28495001
TI - A comparison between swallowing sounds and vibrations in patients with dysphagia.
AB - The cervical auscultation refers to the observation and analysis of sounds or
vibrations captured during swallowing using either a stethoscope or
acoustic/vibratory detectors. Microphones and accelerometers have recently become
two common sensors used in modern cervical auscultation methods. There are open
questions about whether swallowing signals recorded by these two sensors provide
unique or complementary information about swallowing function; or whether they
present interchangeable information. This study aims to compare of swallowing
signals recorded by a microphone and a tri-axial accelerometer from 72 patients
(mean age 63.94 +/- 12.58 years, 42 male, 30 female), who had videofluoroscopic
examination. The participants swallowed one or more boluses of thickened liquids
of different consistencies, including thin liquids, nectar-thick liquids, and
pudding. A comfortable self-selected volume from a cup or a controlled volume by
the examiner from a 5 ml spoon was given to the participants. A broad feature set
was extracted in time, information-theoretic, and frequency domains from each of
881 swallows presented in this study. The swallowing sounds exhibited
significantly higher frequency content and kurtosis values than the swallowing
vibrations. In addition, the Lempel-Ziv complexity was lower for swallowing
sounds than those for swallowing vibrations. To conclude, information provided by
microphones and accelerometers about swallowing function are unique and these two
transducers are not interchangeable. Consequently, the selection of transducer
would be a vital step in future studies.
PMID- 28495003
TI - Viral warts (Human Papilloma Virus) as a potential risk for breast cancer among
younger females.
AB - INTRODUCTION: There have been several reports on the role of human papillomavirus
(HPV) in the etiology of breast cancer. To our knowledge, this is first study to
use disease-disease association data-mining approach to analyzing viral warts and
breast cancer to be conducted in Taiwanese population. MATERIALS AND METHODS: We
analyzed the Taiwan's National Health Insurance database (NHIDM data comprising
of 23 million patient data) to examine the association between viral warts and
female breast carcinoma. The patients were categorized into three groups: breast
cancer only, viral warts only, and those with both breast cancer and viral warts.
The Cox proportion hazard regression analysis was used to measure the effect of
HPV on the time to breast cancer diagnosis. Multivariable analyzes and stratified
analyzes using hazard ratios (HRs) were presented with 95% confidence intervals
(CIs) after adjusting for age, and CCI. RESULT: Among 807,578 HPV population, we
identified 6014 breast cancer cases. The HPV group was associated with a
significantly higher risk of developing breast cancer (HR, 1.18; 95% CI, 1.15
1.21; p< 0.001) compared with the non-HPV group. HPV patients with age group 18
39 was slightly higher risk of breast cancer occurrence (HR, 1.07; 95% CI, 1.01
1.13; p<.05). The risk of breast cancer in 10-year incidence was 7% higher for
females less than 40 years and 23% for over 40 year's patients when compared with
non-HPV patients of the same age group. CONCLUSION: Our study indicates that
women who develop viral warts are at a significantly higher risk of developing
breast cancer than women who have not diagnosed with viral warts. Thus, the
presence of viral warts is a potential risk to breast cancer. Therefore, we
suggest patients diagnosed with viral warts may get early screening for breast
cancer.
PMID- 28495004
TI - Optimized PID control of depth of hypnosis in anesthesia.
AB - BACKGROUND AND OBJECTIVE: This paper addresses the use of proportional-integral
derivative controllers for regulating the depth of hypnosis in anesthesia by
using propofol administration and the bispectral index as a controlled variable.
In fact, introducing an automatic control system might provide significant
benefits for the patient in reducing the risk for under- and over-dosing.
METHODS: In this study, the controller parameters are obtained through genetic
algorithms by solving a min-max optimization problem. A set of 12 patient models
representative of a large population variance is used to test controller
robustness. The worst-case performance in the considered population is minimized
considering two different scenarios: the induction case and the maintenance case.
RESULTS: Our results indicate that including a gain scheduling strategy enables
optimal performance for induction and maintenance phases, separately. Using a
single tuning to address both tasks may results in a loss of performance up to
102% in the induction phase and up to 31% in the maintenance phase. Further on,
it is shown that a suitably designed low-pass filter on the controller output can
handle the trade-off between the performance and the noise effect in the control
variable. CONCLUSIONS: Optimally tuned PID controllers provide a fast induction
time with an acceptable overshoot and a satisfactory disturbance rejection
performance during maintenance. These features make them a very good tool for
comparison when other control algorithms are developed.
PMID- 28495005
TI - Developing a ubiquitous health management system with healthy diet control for
metabolic syndrome healthcare in Taiwan.
AB - BACKGROUND AND OBJECTIVE: Self-management in healthcare can allow patients
managing their health data anytime and everywhere for prevention of chronic
diseases. This study established a prototype of ubiquitous health management
system (UHMS) with healthy diet control (HDC) for people who need services of
metabolic syndrome healthcare in Taiwan. METHODS: System infrastructure comprises
of three portals and a database tier with mutually supportive components to
achieve functionality of diet diaries, nutrition guides, and health risk
assessments for self-health management. With the diet, nutrition, and personal
health database, the design enables the analytical diagrams on the interactive
interface to support a mobile application for diet diary, a Web-based platform
for health management, and the modules of research and development for medical
care. For database integrity, dietary data can be stored at offline mode prior to
transformation between mobile device and server site at online mode. RESULTS: The
UHMS-HDC was developed by open source technology for ubiquitous health management
with personalized dietary criteria. The system integrates mobile, internet, and
electronic healthcare services with the diet diary functions to manage healthy
diet behaviors of users. The virtual patients were involved to simulate the self
health management procedure. The assessment functions were approved by capturing
the screen snapshots in the procedure. The proposed system development was
capable for practical intervention. CONCLUSION: This approach details the
expandable framework with collaborative components regarding the self-developed
UHMS-HDC. The multi-disciplinary applications for self-health management can
support the healthcare professionals to reduce medical resources and improve
healthcare effects for the patient who requires monitoring personal health
condition with diet control. The proposed system can be practiced for
intervention in the hospital.
PMID- 28495006
TI - E-health internationalization requirements for audit purposes.
AB - BACKGROUND AND OBJECTIVE: In the 21st century, e-health is proving to be one of
the strongest drivers for the global transformation of the health care industry.
Health information is currently truly ubiquitous and widespread, but in order to
guarantee that everyone can appropriately access and understand this information,
regardless of their origin, it is essential to bridge the international gap. The
diversity of health information seekers languages and cultures signifies that e
health applications must be adapted to satisfy their needs. METHODS: In order to
achieve this objective, current and future e-health programs should take into
account the internationalization aspects. This paper presents an
internationalization requirements specification in the form of a reusable
requirements catalog, obtained from the principal related standards, and
describes the key methodological elements needed to perform an e-health software
audit by using the internationalization knowledge previously gathered. RESULTS: S
Health, a relevant, well-known Android application that has more than 150 million
users in over 130 countries, was selected as a target for the e-health
internationalization audit method and requirements specification presented above.
This application example helped us to put into practice the proposal and show
that the procedure is realistic and effective. CONCLUSIONS: The approach
presented in this study is subject to continuous improvement through the
incorporation of new knowledge originating from additional information sources,
such as other standards or stakeholders. The application example is useful for
early evaluation and serves to assess the applicability of the
internationalization catalog and audit methodology, and to improve them. It would
be advisable to develop of an automated tool with which to carry out the audit
method.
PMID- 28495007
TI - A lightweight QRS detector for single lead ECG signals using a max-min difference
algorithm.
AB - BACKGROUND AND OBJECTIVES: Detection of the R-peak pertaining to the QRS complex
of an ECG signal plays an important role for the diagnosis of a patient's heart
condition. To accurately identify the QRS locations from the acquired raw ECG
signals, we need to handle a number of challenges, which include noise, baseline
wander, varying peak amplitudes, and signal abnormality. This research aims to
address these challenges by developing an efficient lightweight algorithm for QRS
(i.e., R-peak) detection from raw ECG signals. METHODS: A lightweight real-time
sliding window-based Max-Min Difference (MMD) algorithm for QRS detection from
Lead II ECG signals is proposed. Targeting to achieve the best trade-off between
computational efficiency and detection accuracy, the proposed algorithm consists
of five key steps for QRS detection, namely, baseline correction, MMD curve
generation, dynamic threshold computation, R-peak detection, and error
correction. Five annotated databases from Physionet are used for evaluating the
proposed algorithm in R-peak detection. Integrated with a feature extraction
technique and a neural network classifier, the proposed ORS detection algorithm
has also been extended to undertake normal and abnormal heartbeat detection from
ECG signals. RESULTS: The proposed algorithm exhibits a high degree of robustness
in QRS detection and achieves an average sensitivity of 99.62% and an average
positive predictivity of 99.67%. Its performance compares favorably with those
from the existing state-of-the-art models reported in the literature. In regards
to normal and abnormal heartbeat detection, the proposed QRS detection algorithm
in combination with the feature extraction technique and neural network
classifier achieves an overall accuracy rate of 93.44% based on an empirical
evaluation using the MIT-BIH Arrhythmia data set with 10-fold cross validation.
CONCLUSIONS: In comparison with other related studies, the proposed algorithm
offers a lightweight adaptive alternative for R-peak detection with good
computational efficiency. The empirical results indicate that it not only yields
a high accuracy rate in QRS detection, but also exhibits efficient computational
complexity at the order of O(n), where n is the length of an ECG signal.
PMID- 28495008
TI - A fully automatic approach for multimodal PET and MR image segmentation in gamma
knife treatment planning.
AB - BACKGROUND AND OBJECTIVES: Nowadays, clinical practice in Gamma Knife treatments
is generally based on MRI anatomical information alone. However, the joint use of
MRI and PET images can be useful for considering both anatomical and metabolic
information about the lesion to be treated. In this paper we present a co
segmentation method to integrate the segmented Biological Target Volume (BTV),
using [11C]-Methionine-PET (MET-PET) images, and the segmented Gross Target
Volume (GTV), on the respective co-registered MR images. The resulting volume
gives enhanced brain tumor information to be used in stereotactic neuro
radiosurgery treatment planning. GTV often does not match entirely with BTV,
which provides metabolic information about brain lesions. For this reason, PET
imaging is valuable and it could be used to provide complementary information
useful for treatment planning. In this way, BTV can be used to modify GTV,
enhancing Clinical Target Volume (CTV) delineation. METHODS: A novel fully
automatic multimodal PET/MRI segmentation method for Leksell Gamma Knife(r)
treatments is proposed. This approach improves and combines two computer-assisted
and operator-independent single modality methods, previously developed and
validated, to segment BTV and GTV from PET and MR images, respectively. In
addition, the GTV is utilized to combine the superior contrast of PET images with
the higher spatial resolution of MRI, obtaining a new BTV, called BTVMRI. A total
of 19 brain metastatic tumors, undergone stereotactic neuro-radiosurgery, were
retrospectively analyzed. A framework for the evaluation of multimodal PET/MRI
segmentation is also presented. Overlap-based and spatial distance-based metrics
were considered to quantify similarity concerning PET and MRI segmentation
approaches. Statistics was also included to measure correlation among the
different segmentation processes. Since it is not possible to define a gold
standard CTV according to both MRI and PET images without treatment response
assessment, the feasibility and the clinical value of BTV integration in Gamma
Knife treatment planning were considered. Therefore, a qualitative evaluation was
carried out by three experienced clinicians. RESULTS: The achieved experimental
results showed that GTV and BTV segmentations are statistically correlated
(Spearman's rank correlation coefficient: 0.898) but they have low similarity
degree (average Dice Similarity Coefficient: 61.87 +/- 14.64). Therefore, volume
measurements as well as evaluation metrics values demonstrated that MRI and PET
convey different but complementary imaging information. GTV and BTV could be
combined to enhance treatment planning. In more than 50% of cases the CTV was
strongly or moderately conditioned by metabolic imaging. Especially, BTVMRI
enhanced the CTV more accurately than BTV in 25% of cases. CONCLUSIONS: The
proposed fully automatic multimodal PET/MRI segmentation method is a valid
operator-independent methodology helping the clinicians to define a CTV that
includes both metabolic and morphologic information. BTVMRI and GTV should be
considered for a comprehensive treatment planning.
PMID- 28495010
TI - Predictive Analytics through Machine Learning in the clinical settings.
PMID- 28495009
TI - A two-step convolutional neural network based computer-aided detection scheme for
automatically segmenting adipose tissue volume depicting on CT images.
AB - Accurately assessment of adipose tissue volume inside a human body plays an
important role in predicting disease or cancer risk, diagnosis and prognosis. In
order to overcome limitation of using only one subjectively selected CT image
slice to estimate size of fat areas, this study aims to develop and test a
computer-aided detection (CAD) scheme based on deep learning technique to
automatically segment subcutaneous fat areas (SFA) and visceral fat areas (VFA)
depicting on volumetric CT images. A retrospectively collected CT image dataset
was divided into two independent training and testing groups. The proposed CAD
framework consisted of two steps with two convolution neural networks (CNNs)
namely, Selection-CNN and Segmentation-CNN. The first CNN was trained using 2,240
CT slices to select abdominal CT slices depicting SFA and VFA. The second CNN was
trained with 84,000pixel patches and applied to the selected CT slices to
identify fat-related pixels and assign them into SFA and VFA classes. Comparing
to the manual CT slice selection and fat pixel segmentation results, the accuracy
of CT slice selection using the Selection-CNN yielded 95.8%, while the accuracy
of fat pixel segmentation using the Segmentation-CNN was 96.8%. This study
demonstrated the feasibility of applying a new deep learning based CAD scheme to
automatically recognize abdominal section of human body from CT scans and segment
SFA and VFA from volumetric CT data with high accuracy or agreement with the
manual segmentation results.
PMID- 28495011
TI - Solitary fibrous tumour of pleura: CT differentiation of benign and malignant
types.
AB - AIM: To analyse and compare the computed tomography (CT) features of benign and
malignant types of histopathologically proven cases of solitary fibrous tumours
of pleura (SFTP). MATERIALS AND METHODS: Retrospective analysis of preoperative
CT images of 28 cases of histopathologically proven and classified SFTP from
three participating institutions was performed. Patient demographics and lesion
characteristics including size, borders, presence of a pedicle, extension into
the fissure, attenuation, enhancement, pleural effusion, and calcifications were
recorded and correlated with the final histopathological diagnosis. Type and
results of preoperative biopsy were also recorded. Follow-up imaging and the
clinical charts were reviewed to identify recurrence. RESULTS: Out of 28 cases
(15 women and 13 men), 18 were proven to be benign and 10 were malignant. The
mean age of patients was 58.1+/-15.9 and 66.5+/-11.8 years (p=0.1564) for benign
and malignant tumours, respectively. The median (interquartile range) diameter
was 6.05 (3.2-10.9) cm for benign and 15.7 (7.1-17.5) cm for malignant type
tumours (p=0.0291). Tumours had lobulate borders in 28% (5/18) of benign cases
and in 80% (8/10) of malignant cases (p=0.0163). Extension into adjacent fissure
was seen in 22% (4/18) of benign lesions and 40% (4/10) of malignant lesions
(p=0.40). A pedicle was present in 17% (3/18) of benign and 10% (1/10) of
malignant lesions (p=1). Heterogeneous attenuation was present in 61% (11/18) of
benign and 90% (9/10) of malignant lesions (p=0.19). Calcification was present in
17% (3/18) of benign tumours and in 70% (7/10) of malignant tumours (p=0.0113).
Pleural effusion was present in 6% (1/18) of benign and 40% (4/10) of malignant
lesions (p=0.04). Only 1/13 preoperative fine-needle aspirates yielded diagnosis
of SFTP. Preoperative diagnosis of SFTP was made in all cases (11/11) with core
biopsies. At follow-up (1-10 years, mean 3 years), local recurrence occurred in
3/6 (50%) patients with malignant SFTP and in none of the 10 patients with benign
SFTP. CONCLUSION: No definite imaging feature to differentiate benign from
malignant SFTP was found. Large size, lobulate borders, presence of
calcification, and ipsilateral pleural effusion were the only CT features
predictive of malignancy. In suspected cases, core biopsies should be performed
rather than fine-needle aspiration.
PMID- 28495012
TI - What do clinicians treat: Diagnoses or symptoms? The incremental validity of a
symptom-based, dimensional characterization of emotional disorders in predicting
medication prescription patterns.
AB - BACKGROUND: Although practice guidelines are based on disorders specified in
diagnostic manuals, such as the DSM, practitioners appear to follow symptoms when
making treatment decisions. Psychiatric medication is generally prescribed in a
transdiagnostic manner, further highlighting how symptoms, not diagnoses, often
guide clinical practice. A quantitative approach to nosology promises to provide
better guidance as it describes psychopathology dimensionally and its
organization reflects patterns of covariation among symptoms. AIM: To investigate
whether a quantitative classification of emotional disorders can account for
naturalistic medication prescription patterns better than traditional diagnoses.
METHODS: Symptom dimensions and DSM diagnoses of emotional disorders, as well as
prescribed medications, were assessed using interviews in a psychiatric
outpatient sample (N=318, mean age 42.5years old, 59% female, 81% Caucasian).
RESULTS: Each diagnosis was associated with prescription of multiple medication
classes, and most medications were associated with multiple disorders. This was
largely due to heterogeneity of clinical diagnoses, with narrow, homogenous
dimensions underpinning diagnoses showing different medication profiles. Symptom
dimensions predicted medication prescription better than DSM diagnoses,
irrespective of whether this was examined broadly across all conditions, or
focused on a specific disorder and medication indicated for it. CONCLUSIONS:
Psychiatric medication was prescribed in line with symptoms rather than DSM
diagnoses. A quantitative approach to nosology may better reflect treatment
planning and be a more effective guide to pharmacotherapy than traditional
diagnoses. This adds to a diverse body of evidence about superiority of the
quantitative system in practical applications and highlights its potential to
improve psychiatric care.
PMID- 28495014
TI - Bisphosphonates or denosumab discontinuation and risk of fractures.
PMID- 28495013
TI - The ACTTION-APS-AAPM Pain Taxonomy (AAAPT) Multidimensional Approach to
Classifying Acute Pain Conditions.
AB - OBJECTIVE: With the increasing societal awareness of the prevalence and impact of
acute pain, there is a need to develop an acute pain classification system that
both reflects contemporary mechanistic insights and helps guide future research
and treatment. Existing classifications of acute pain conditions are limiting,
with a predominant focus on the sensory experience (eg, pain intensity) and
pharmacologic consumption. Consequently, there is a need to more broadly
characterize and classify the multidimensional experience of acute pain. SETTING:
Consensus report following expert panel involving the Analgesic, Anesthetic, and
Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks
(ACTTION), American Pain Society (APS), and American Academy of Pain Medicine
(AAPM). METHODS: As a complement to a taxonomy recently developed for chronic
pain, the ACTTION public-private partnership with the US Food and Drug
Administration, the APS, and the AAPM convened a consensus meeting of experts to
develop an acute pain taxonomy using prevailing evidence. Key issues pertaining
to the distinct nature of acute pain are presented followed by the agreed-upon
taxonomy. The ACTTION-APS-AAPM Acute Pain Taxonomy will include the following
dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4)
impact/functional consequences, and 5) putative pathophysiologic pain mechanisms.
Future efforts will consist of working groups utilizing this taxonomy to develop
diagnostic criteria for a comprehensive set of acute pain conditions.
PERSPECTIVE: The ACTTION-APS-AAPM Acute Pain Taxonomy (AAAPT) is a
multidimensional acute pain classification system designed to classify acute pain
along the following dimensions: 1) core criteria, 2) common features, 3)
modulating factors, 4) impact/functional consequences, and 5) putative
pathophysiologic pain mechanisms. CONCLUSIONS: Significant numbers of patients
still suffer from significant acute pain, despite the advent of modern multimodal
analgesic strategies. Mismanaged acute pain has a broad societal impact as
significant numbers of patients may progress to suffer from chronic pain. An
acute pain taxonomy provides a much-needed standardization of clinical diagnostic
criteria, which benefits clinical care, research, education, and public policy.
For the purposes of the present taxonomy, acute pain is considered to last up to
seven days, with prolongation to 30 days being common. The current understanding
of acute pain mechanisms poorly differentiates between acute and chronic pain and
is often insufficient to distinguish among many types of acute pain conditions.
Given the usefulness of the AAPT multidimensional framework, the AAAPT undertook
a similar approach to organizing various acute pain conditions.
PMID- 28495015
TI - Erratum to 'Pleiotropic protective effects of vitamin D against high fat diet
induced metabolic syndrome in rats: One for all' [Eur. J. Pharmacol. 792 (2016)
38-47].
PMID- 28495016
TI - Corrigendum to "Diethyl-4,4'-dihydroxy-8,3'-neolign-7,7'-dien-9,9'-dionate
exhibits antihypertensive activity in rats through increase in intracellular cGMP
level and blockade of calcium channels" [Eur. J. Pharmacol. 799 (2017) 84-93].
PMID- 28495017
TI - Graphene for the development of the next-generation of biocomposites for dental
and medical applications.
AB - OBJECTIVE: Graphene and its derivatives, graphene oxide (GO) and reduced graphene
oxide (rGO), are 2D carbon-based materials with remarkable physical, chemical and
biological properties. Graphene sheets have high specific surface area and
mechanical strength. Moreover, they have been shown to influence the
differentiation of stem cells and to improve properties of biomaterials. METHODS:
Here, we present the recent achievements on the use of graphene and its
derivatives to improve properties and enhance bioactivity of biomaterials. We
also discuss the biosafety constraints to be solved to translate these
carbonaceous materials to the clinic. RESULTS: Graphene and its derivatives can
be functionalized and further modified with several bioactive molecules. They can
be combined with several biomaterials used in regenerative and reconstructive
dentistry and medicine. The resultant graphene-modified composites often present
improved physico-mechanical properties and enhanced bioactivity. Moreover,
graphene-modified composites are promising candidates to deliver growth factors,
drugs and others bioactive compounds. SIGNIFICANCE: Graphene can improve the
physical, chemical and mechanical properties of biomaterials. As it can be
functionalized and combined with several biomolecules, graphene holds enormous
potential to be used as drug carriers or substrates and scaffolds for cell-based
tissue engineering strategies.
PMID- 28495018
TI - Effects of leptin administration on development, vascularization and function of
Corpus luteum in alpacas submitted to pre-ovulatory fasting.
AB - The objective of this study was to determine the effect of leptin administration
on the development, vascularization and function of Corpus luteum (CL) in alpacas
submitted to pre-ovulatory fasting. Fourteen alpacas were kept in fasting
conditions for 72h and received five doses of o-leptin (2MUg/kg e.v.; Leptin
group) or saline (Control group) every 12h. Ovulation was induced with a GnRH
dose (Day 0). The ovaries were examined every other day by trans-rectal
ultrasonography (7.5MHz; mode B and power Doppler) from Day 0 to 13 to determine
the pre-ovulatory follicle diameter and ovulation, and then to monitor CL
diameter and vascularization until the regression phase. Serial blood samples
were taken after GnRH treatment to determine plasma LH concentration; and every
other day from Days 1 to 13 to determine plasma progesterone and leptin
concentrations. The pre-ovulatory follicle and CL diameter, LH, progesterone and
leptin plasma concentrations were not affected by treatment (P>0.05). The
vascularization area of the CL was, nevertheless, affected by the treatment
(P<0.01) with significant differences between groups at Days 3, 7 and 9 (P<0.05).
The Leptin group had a larger maximum vascularization area (0.67+/-0.1 compared
with 0.35+/-0.1cm2; P<0.05). In addition, there was a positive correlation
between CL vascularization, CL diameter and plasma progesterone. The exogenous
administration of leptin during pre-ovulatory fasting increased the
vascularization of the CL in alpacas in vivo.
PMID- 28495019
TI - Response to letter: Psychometric properties of the Tinnitus Functional Index
(TFI): Assessment in a UK research volunteer population.
PMID- 28495020
TI - UPLC-MS/MS method for determination of sofosbuvir in human plasma.
AB - INTRODUCTION: A sensitive and rapid method for quantitation of Sofosbuvir in
human plasma has been established using ultra performance liquid chromatography
electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). MATERIALS AND
METHODS: Sofosbuvir d3 was used as an internal standard. Sofosbuvir and internal
standard in plasma sample were extracted using ethyl acetate (liquid liquid
extraction). A centrifuged upper layer was then evaporated and reconstituted with
the mobile phase of 0.5% formic acid: methanol (30:70, v/v). The reconstituted
samples were injected into a Gemini C18 (50*4.6mm, 5MUm) column. RESULTS: Using
MS/MS in the multiple reaction monitoring mode, Sofosbuvir and Sofosbuvir d3 were
detected without severe interferences from human plasma matrix. Sofosbuvir
produced a protonated precursor ion ([M+H]+) at m/z 428.35 and a corresponding
product ion at m/z 279.26. The internal standard produced a protonated precursor
ion ([M+H]+) at m/z 431.38 and a corresponding product ion at m/z 282.37. The
calibration curves for the analyte was linear (R2>=0.9956, n=4) over the
concentration range of 4.063-8000.010ng/mL. Stability studies revealed that
Sofosbuvir was stable in plasma during bench top (7h at room temperature), in
injector (20h), at the end of five successive freeze and thaw cycles and long
term at -70 degrees C+/-15 degrees C for 15 days. CONCLUSION: The developed
method was validated as per the guidelines of USFDA and the obtained results were
found to be within the limits and could be successfully employed for the
determination of Sofosbuvir in human plasma for regular and pharmacokinetic
studies.
PMID- 28495021
TI - Damage control and intramedullary nailing for long bone fractures in polytrauma
patients.
AB - The early fracture treatment in patients with multiple injuries should be focused
on damage control. The fracture type and its location, local soft tissue
condition as well as the patient's physiological condition shall determine the
time and type of fracture treatment. Prevention of local and systemic
complications must be immediately considered and included in the treatment
planning. The use of external fixator (ExFix), which will be replaced by IM
implants in most cases at a later stage, provides adequate temporary fracture
stabilization with less collateral damage. Good clinical results can be expected
in patients with long bone fractures if the principles of damage control surgery
are applied and local complications are prevented through proper reduction, firm
fixation, early soft tissue reconstruction, and early rehabilitation.
PMID- 28495023
TI - Reduction of SPECT MPI Radiation Dose Using Contemporary Protocols and
Technology.
PMID- 28495022
TI - Delineating the joint hierarchical structure of clinical and personality
disorders in an outpatient psychiatric sample.
AB - BACKGROUND: A large body of research has focused on identifying the optimal
number of dimensions - or spectra - to model individual differences in
psychopathology. Recently, it has become increasingly clear that ostensibly
competing models with varying numbers of spectra can be synthesized in
empirically derived hierarchical structures. METHODS AND MATERIALS: We examined
the convergence between top-down (bass-ackwards or sequential principal
components analysis) and bottom-up (hierarchical agglomerative cluster analysis)
statistical methods for elucidating hierarchies to explicate the joint
hierarchical structure of clinical and personality disorders. Analyses examined
24 clinical and personality disorders based on semi-structured clinical
interviews in an outpatient psychiatric sample (n=2900). RESULTS: The two methods
of hierarchical analysis converged on a three-tier joint hierarchy of
psychopathology. At the lowest tier, there were seven spectra - disinhibition,
antagonism, core thought disorder, detachment, core internalizing, somatoform,
and compulsivity - that emerged in both methods. These spectra were nested under
the same three higher-order superspectra in both methods: externalizing, broad
thought dysfunction, and broad internalizing. In turn, these three superspectra
were nested under a single general psychopathology spectrum, which represented
the top tier of the hierarchical structure. CONCLUSIONS: The hierarchical
structure mirrors and extends upon past research, with the inclusion of a novel
compulsivity spectrum, and the finding that psychopathology is organized in three
superordinate domains. This hierarchy can thus be used as a flexible and
integrative framework to facilitate psychopathology research with varying levels
of specificity (i.e., focusing on the optimal level of detailed information,
rather than the optimal number of factors).
PMID- 28495024
TI - Live-Cell Nanoscopy in Antiadhesion Therapy.
AB - Live-cell nanoscopy has contributed significantly to assessing the inhibition of
adhesion of uropathogenic Escherichia coli and Staphylococcus aureus by
glycoconjugates and monoclonal antibodies, respectively, and of S. aureus surface
attachment and cell-cell association by a synthetic peptide. This new technology
shows promise for the development of antiadhesion therapies against bacterial
pathogens.
PMID- 28495025
TI - The cognitive neuroscience of source memory: Moving the ball forward.
PMID- 28495026
TI - Neck-Related Physical Function, Self-Efficacy, and Coping Strategies in Patients
With Cervical Radiculopathy: A Randomized Clinical Trial of Postoperative
Physiotherapy.
AB - OBJECTIVE: The purpose of this study was to compare postoperative rehabilitation
with structured physiotherapy to the standard approach in patients with cervical
radiculopathy (CR) in a prospective randomized study at 6 months follow-up based
on measures of neck-related physical function, self-efficacy, and coping
strategies. METHODS: Patients with persistent CR and scheduled for surgery (N =
202) were randomly assigned to structured postoperative physiotherapy or a
standard postoperative approach. Structured postoperative physiotherapy combined
neck-specific exercises with a behavioral approach. Baseline, 3-month, and 6
month evaluations included questionnaires and clinical examinations. Neck muscle
endurance, active cervical range of motion, self-efficacy, pain catastrophizing
(CSQ-CAT), perceived control over pain, and ability to decrease pain were
analyzed for between-group differences using complete case and per-protocol
approaches. RESULTS: No between-group difference was reported at the 6-month
follow-up (P = .05-.99), but all outcomes had improved from baseline (P < .001).
Patients undergoing structured postoperative physiotherapy with >=50% attendance
at treatment sessions had larger improvements in CSQ-CAT (P = .04) during the
rehabilitation period from 3 to 6 months after surgery compared with the patients
who received standard postoperative approach. CONCLUSIONS: No between-group
difference was found at 6 months after surgery based on measures of neck-related
physical function, self-efficacy, and coping strategies. However, the results
confirm that neck-specific exercises are tolerated by patients with CR after
surgery and may suggest a benefit from combining surgery with structured
postoperative physiotherapy for patients with CR.
PMID- 28495027
TI - Medial Femoral Condyle Microvascular Bone Transfer as a Treatment for Capitate
Avascular Necrosis: Surgical Technique and Case Report.
AB - : Avascular necrosis (AVN) of the capitate is a rare clinical entity for which a
variety of treatment options have been described, ranging from immobilization to
microvascular bone transfer. Outcomes following medial femoral condyle
corticocancellous free flap reconstruction have not been reported for this
specific pathology. We present the case of a 16-year-old girl with posttraumatic
capitate AVN who was treated with curettage and medial femoral condyle
corticocancellous vascularized bone grafting. At 18 months after surgery, the
patient remains pain-free and had resumed all activities including lifeguarding
by 6 months after surgery. This microsurgical technique, described previously for
AVN of the scaphoid and lunate, may be applied in a similar fashion for the
capitate with promising clinical results. TYPE OF STUDY/LEVEL OF EVIDENCE:
Therapeutic V.
PMID- 28495028
TI - Real-world Clinical Outcomes Among Patients With Type 2 Diabetes Receiving
Canagliflozin at a Specialty Diabetes Clinic: Subgroup Analysis by Baseline HbA1c
and Age.
AB - PURPOSE: Canagliflozin, a sodium glucose co-transporter 2 inhibitor developed for
the treatment of type 2 diabetes mellitus (T2DM), has demonstrated effectiveness
in patients with T2DM receiving care at a specialty diabetes clinic. We report
the outcomes in these patients in subgroups classified by baseline hemoglobin A1c
(HbA1c) and age. METHODS: This subgroup analysis was based on a review of data
from the electronic health records of adults with T2DM who were prescribed
canagliflozin at a specialty diabetes clinic and who returned for >=1 follow-up
office visit. Mean changes from baseline to the first and second follow-up office
visits in HbA1c, body weight, and systolic and diastolic blood pressure (BP) were
calculated in each subgroup classified by baseline HbA1c (>=7.0%, >=8.0%, and
>9.0%) and age (<65 and >=65 years). FINDINGS: Of the 462 patients included in
the study, 430, 305, and 169 patients had baseline HbA1c >=7.0%, >=8.0%, and
>9.0%, respectively; 396 and 66 patients were aged <65 and >=65 years,
respectively. With canagliflozin use, patients across subgroups classified by
baseline HbA1c and age experienced clinically and statistically significant
reductions from baseline in HbA1c, body weight, and systolic BP that were
sustained over 2 office visits; diastolic BP was also reduced across baseline
HbA1c and age subgroups. Greater reductions in HbA1c were seen among the
canagliflozin-treated patients with higher baseline HbA1c and among younger
versus older patients. IMPLICATION: These findings from clinical practice
demonstrate real-world effectiveness of canagliflozin in lowering HbA1c, body
weight, and systolic BP among patients with T2DM, regardless of baseline HbA1c
levels or age.
PMID- 28495029
TI - The Pharmacokinetics of the CYP3A Substrate Midazolam After Steady-state Dosing
of Delafloxacin.
AB - PURPOSE: Delafloxacin is a novel anionic fluoroquinolone in Phase III development
for the treatment of serious skin infections. The objective of this study was to
evaluate the effects of delafloxacin on the pharmacokinetics of midazolam, a
cytochrome P450 (CYP) 3A substrate. METHODS: CYP3A activity using midazolam as a
probe was assessed before and after multiple doses of delafloxacin to reach
steady state. In this nonrandomized, open-label, single-sequence, Phase I study,
22 healthy male and female subjects were administered a single 5-mg oral dose of
midazolam on days 1 and 8, with oral delafloxacin 450 mg every 12 hours
administered from days 3 to 8. Full pharmacokinetic profiles were obtained on
days 1 and 8 (midazolam and 1-hydroxymidazolam) and days 3 and 7 (delafloxacin).
FINDINGS: The geometric mean ratios (90% CIs) for AUC0-infinity and Cmax of
midazolam coadministered with delafloxacin versus midazolam alone were 89.4 (83.2
96.0) and 93.6 (83.7-104.6). Similarly, the geometric ratio for the AUC0-infinity
of 1-hydroxymidazolam, the primary metabolite of midazolam, was 105.7 (97.7
114.3); the ratio of Cmax was not equivalent at 116.1 (101.7-132.4), which was
outside the CI of 80% to 125%. Multiple doses of oral delafloxacin for 6 days
were generally well tolerated. IMPLICATIONS: Steady-state dosing of delafloxacin
produced no significant changes in midazolam pharmacokinetics, except for a small
but not clinically relevant change in the Cmax of 1-hydroxymidazolam.
ClinicalTrials.gov identifier: NCT02505997.
PMID- 28495030
TI - Intubation and salicylate overdose.
PMID- 28495031
TI - A pilot mobile integrated healthcare program for frequent utilizers of emergency
department services.
AB - PURPOSE: To examine whether or not a mobile integrated health (MIH) program may
improve health-related quality of life while reducing emergency department (ED)
transports, ED admissions, and inpatient hospital admissions in frequent
utilizers of ED services. METHODS: A small retrospective evaluation assessing pre
and post-program quality of life, ED transports, ED admissions, and inpatient
hospital admissions was conducted in patients who frequently used the ED for non
emergent or emergent/primary care treatable conditions. RESULTS: Pre- and post
program data available on 64 program completers are reported. Of those with
mobility problems (n=42), 38% improved; those with problems performing usual
activities (N=45), 58% reported improvement; and of those experiencing moderate
to extreme pain or discomfort (N=48), 42% reported no pain or discomfort after
program completion. Frequency of ED transports decreased (5.34+/-6.0 vs. 2.08+/
3.3; p <0.000), as did ED admissions (9.66+/-10.2 vs. 3.30+/-4.6; p<0.000), and
inpatient hospital admissions (3.11+/-5.5 vs. 1.38+/-2.5; p=0.003). CONCLUSION:
Results suggest that MIH participation is associated with improved quality of
life, reduced ED transports, ED admissions, and inpatient hospital admissions.
The MIH program may have potential to improve health outcomes in patients who are
frequent ED users for non-emergent or emergent/primary care treatable conditions
by teaching them how to proactively manage their health and adhere to therapeutic
regimens. Programmatic reasons for these improvements may include psychosocial
bonding with participants who received in-home care, health coaching, and the MIH
team's 24/7 availability that provided immediate healthcare access.
PMID- 28495032
TI - Meat science from 1976: A history of the journal.
AB - The journal Meat Science was first published in 1976/77 and it initially
comprised 4 issues per year. The first issue contained 4 papers and the first
volume (4 issues) contained 27 articles, a mixture of papers and research notes.
Its growth/popularity increased, and it has continued to thrive and in 2016 of
the 1010 papers processed 292 were accepted. Over 90% of the papers published in
the first volume were concerned with muscle biochemistry/meat properties. During
the last years of the 20th century, meat products and their properties became a
far larger proportion of the submissions as did those concerned with nutrition
and safety. More recently there has been a resurgence of papers concerned with
meat quality. Over the last 40years, the journal has reported on the major
developments in meat science research and this paper will discuss both the
history of the journal, and aspects of meat research as reflected in its
publications. Possible future research trends are also discussed.
PMID- 28495033
TI - Clinical applications of 3-dimensional printing in radiation therapy.
AB - Three-dimensional (3D) printing is suitable for the fabrication of complex
radiotherapy bolus. Although investigated from dosimetric and feasibility
standpoints, there are few reports to date of its use for actual patient
treatment. This study illustrates the versatile applications of 3D printing in
clinical radiation oncology through a selection of patient cases, namely, to
create bolus for photon and modulated electron radiotherapy (MERT), as well as
applicators for surface high-dose rate (HDR) brachytherapy. Photon boluses were
3D-printed to treat a recurrent squamous cell carcinoma (SCC) of the nasal septum
and a basal cell carcinoma (BCC) of the posterior pinna. For a patient with a
mycosis fungoides involving the upper face, a 3D-printed MERT bolus was used. To
treat an SCC of the nose, a 3D-printed applicator for surface brachytherapy was
made. The structures' fit to the anatomy and the radiotherapy treatment plans
were assessed. Based on the treatment planning computed tomography (CT), the size
of the largest air gap at the interface of the 3D-printed structure was 3 mm for
the SCC of the nasal septum, 3 mm for the BCC of the pinna, 2 mm for the mycosis
fungoides of the face, and 2 mm for the SCC of the nose. Acceptable treatment
plans were obtained for the SCC of the nasal septum (95% isodose to 99.8% of
planning target volume [PTV]), the BCC of the pinna (95% isodose to 97.7% of
PTV), and the mycosis fungoides of the face (90% isodose to 92.5% of PTV). For
the latter, compared with a plan with a uniform thickness bolus, the one
featuring the MERT bolus achieved relative sparing of all the organs at risk
(OARs) distal to the target volume, while maintaining similar target volume
coverage. The surface brachytherapy plan for the SCC of the nose had adequate
coverage (95% isodose to 95.6% of clinical target volume [CTV]), but a relatively
high dose to the left eye, owing to its proximity to the tumor. 3D printing can
be implemented effectively in the clinical setting to create highly conformal
bolus for photon and MERT, as well as applicators for surface brachytherapy.
PMID- 28495034
TI - [Presence of Acanthamoeba spp. in watering trough in La Pampa province,
Argentina].
AB - Free-living Amoebae of Acanthamoeba genus include non-pathogenic and pathogenic
strains that are currently classified in 18 different genotypes, T1-T18. In this
study, a survey was carried out to evaluate the presence of Acanthamoeba strains
inwatering trough sample in La Pampa province, Argentina. Sample were inoculated
onto non-nutrient agar plates and were checked for the presence of Acanthamoeba.
Polymerase chain reaction was performed with genus-specific primers JDP1/JDP2,
followed by direct sequencing of the polymerase chain reaction product for
molecular identification. Sequencing results revealed the presence of T4, T5 and
T15 genotypes within the studied samples. Sequencing revealed presence of T4, T5
and T15 in the samples studied genotypes, the most frequent T4. Our study reveals
importance of the presence of Acanthamoeba in the livestock environment and the
need for further studies to associate the presence of these organisms and the
role in veterinary pathology. To the best of our knowledge, this is the first
report demonstrating the presence Acanthamoeba in La Pampa province and the first
study at the genotype level in Argentina.
PMID- 28495035
TI - Selection of Bacillus thuringiensis strains toxic to cotton boll weevil
(Anthonomus grandis, Coleoptera: Curculionidae) larvae.
AB - Preliminary bioassays with whole cultures (WC) of 124 Bacillus thuringiensis
strains were performed with neonate larvae of Anthonomus grandis, a major cotton
pest in Argentina and other regions of the Americas. Three exotic and four native
strains were selected for causing more than 50% mortality. All of them were beta
exotoxin producers. The native strains shared similar morphology of parasporal
crystals, similar protein pattern and identical insecticidal gene profiles. These
features resembled Lepidoptera-toxic strains. Furthermore, these strains showed a
Rep-PCR pattern identical to lepidoptericidal strain HD-1, suggesting that these
strains may belong to serovar kurstaki. However, some differences were observed
in the plasmid profiles and in the production of beta-exotoxin. To determine the
culture fractions where the insecticidal metabolites were present, bioassays
including resuspended spore-crystal pellets, filtered supernatants (FS) were
compared with those of WC. Both fractions tested showed some level of
insecticidal activity. The results may suggest that the main toxic factors can be
found in FS and could be directly correlated with the presence of beta-exotoxin.
Based on the bioassays with FS and autoclaved FS, the participation of
thermolabile virulence factors such as Cry1I in toxicity is neither discarded. In
the selected strains, beta-exotoxin would be the major associated virulence
factor; therefore, their use in biological control of A. grandis should be
restricted. Nevertheless, these strains could be the source of genes (e.g.,
cry1Ia) to produce transgenic cotton plants resistant to this pest.
PMID- 28495036
TI - Fungal endophytes isolated from Protium heptaphyllum and Trattinnickia rhoifolia
as antagonists of Fusarium oxysporum.
AB - Control of fungal pathogens is mainly addressed by the use of chemically
synthesized fungicides which result in environmental pollution, developing
resistance after prolonged use. In this context, endophytes have been recognized
as potential biocontrollers, and also as a promising source of antifungal
metabolites. Therefore, as part of our research on phytopathogen controllers, 355
fungal endophytes were isolated from Protium heptaphyllum and Trattinnickia
rhoifolia (Burseraceae), both ethnobotanically important tree species that
produce secondary metabolites of agronomic and industrial interest. Endophytes
were tested by in vitro dual culture against Fusarium oxysporum, a phytopathogen
of agronomic importance. Five endophytes exerted at least 40% inhibition on F.
oxysporum growth. Ethyl acetate (EtOAc) extracts were obtained from the most
active antagonistic fungi, after growing them in three different liquid media.
The extracts were tested against a conidial suspension of F. oxysporum by direct
bioautography. Two extracts derived from fungi identified as Chaetomium globosum,
F211_UMNG and Meyerozima sp. F281_UMNG showed inhibition of pathogen growth.
Isolate C. globosum, F211_UMNG was selected for a chemical analysis by RP-HPLC
DAD-ESI-MS and antifungal molecules such as cladosporin, chaetoatrosin A and
chaetoviridin A were annotated and identified based on their MS data.
PMID- 28495037
TI - Efforts to Increase Global Food Security: Implications for International
Nutrition Education.
PMID- 28495038
TI - More Than Reading, Writing, and Arithmetic.
PMID- 28495039
TI - Emotional Symptoms and Dietary Patterns in Early Adolescence: A School-Based
Follow-up Study.
AB - OBJECTIVE: To examine the relationship between early emotional symptoms and
dietary patterns over 3 years in a school-based sample. DESIGN: Three-year
longitudinal prospective study. SETTING: Thirteen schools in Reus, Spain.
PARTICIPANTS: From a sample of 562 preadolescents with and without emotional
symptoms, 165 were observed and were classified as either showing (n = 100) or
not showing emotional symptoms (n = 65). MAIN OUTCOME MEASURE: Emotional symptoms
were assessed at baseline and after 1 and 3 years. In the third year, data were
collected on food consumption, adherence to the Mediterranean diet (MD), and
physical activity. ANALYSIS: Dietary patterns were created by principal component
analysis. Multivariate logistic regression was conducted with P < .05 considered
significant. RESULTS: Girls with emotional symptoms scored significantly lower in
assessments for MD (score of 5.41 +/- 2.19) and physical activity (score of 4.97
+/- 2.05) than did girls who had no emotional symptoms (scores: MD, 6.19 +/-
1.67; physical activity: 5.86 +/- 1.94). Approximately 39.68% of girls with
emotional symptoms showed high adherence to a sweet and fatty food pattern. After
adjusted logistic regression, girls with emotional symptoms were 4 times as
likely to have high adherence to a sweet and fatty food pattern (odds ratio,
4.79; 95% confidence interval, 1.55-15.10). No differences were observed among
boys. CONCLUSIONS AND IMPLICATIONS: Girls with emotional symptoms during early
adolescence have high adherence to a pattern rich in sweet and fat foods and low
adherence to MD, and engage in low levels of physical activity. These findings
highlight the importance of managing emotional distress to prevent it from having
a negative effect on eating behavior.
PMID- 28495040
TI - Overweight and Obesity, Weight Perception, and Weight Management Practices Among
Supplemental Nutrition Assistance Program-Education (SNAP-Ed) Participants in
Georgia: A Needs Assessment.
AB - OBJECTIVE: Examine associations among weight status, weight perception, and
weight management practices of Supplemental Nutrition Assistance Program
Education (SNAP-Ed) participants in Georgia. METHODS: Self-reported weight,
height, and weight-related practices were assessed and analyzed in 270 SNAP-Ed
participants. RESULTS: Almost three quarters of the sample self-reported
overweight or obesity. Among overweight and obese subjects, 39% and 69%,
respectively, accurately perceived themselves as overweight. More than half of
the sample desired weight loss and 44% had attempted weight loss in the past
year. Overweight/obese subjects who accurately perceived their weight were more
likely to desire and to have attempted weight loss than those who under-perceived
their weight. Approximately 58% of all subjects who had attempted to lose weight
reported use of both methods suggested for weight loss: exercise and dietary
changes. CONCLUSIONS AND IMPLICATIONS: The high prevalence of self-reported
overweight/obesity combined with a desire to lose weight among the study sample
demonstrated the necessity to develop SNAP-Ed curricula emphasizing weight
management.
PMID- 28495041
TI - Staff Workshop Improves Child Care Center Menus in South Central Texas: A Best
Food for Families, Infants, and Toddlers (Best Food FITS) Intervention.
AB - OBJECTIVE: To assess the efficacy of an educational workshop for child care
center staff to improve menus. METHODS: Staff from 18 centers attended a
nutrition educational workshop that included an activity that compared center
menus to MyPlate standards. Four weeks of menus collected before and after the
workshop were imported into SuperTracker; the Food Details report produced menu
data clustered by day and center. Changes in pre-post menus were assessed using
Healthy Eating Index scores and the SAS software macro, MIXCORR. RESULTS: After
the workshop, there was a lower probability that fruit juice (P = .03) and
starchy vegetables (P = .004) and a higher probability that non-starchy
vegetables (P < .001) and whole grains (P = .004) were on menus; amounts of
refined grains (P = .004), savory snacks (P < .001), and cheese (P = .004) were
significantly lower. Total Healthy Eating Index scores improved after the
workshop (P = .009). CONCLUSIONS AND IMPLICATIONS: Comparing 4 weeks of menus
revealed menu changes. Workshop interventions show promise for improving
children's health.
PMID- 28495042
TI - Confirming the Reliability and Validity of Others' Evaluation Tools Before
Adopting for Your Programs.
AB - OBJECTIVE: To confirm the reliability and validity of a previously validated
evaluation instrument in a new context. METHODS: In a cross-sectional study, the
processes and results of testing Cooking Matters' (CM) use of the Expanded Food
and Nutrition Education Program's Behavior Checklist as a retrospective
pretest/posttest were described. The researchers determined reliability, face and
content validity, and response-shift bias with 95 CM participants. RESULTS: Most
items had acceptable face validity and moderate reliability; other items lacked
reliability, or face or content validity (were unrelated to the CM curriculum).
CONCLUSIONS AND IMPLICATIONS: Proper match between evaluation tools and curricula
is needed for appropriate program assessment without which outcome data can be
misleading or potentially invalid. Confirmation of validity is essential when
adopting others' evaluation tools in new contexts, particularly for programs with
widespread use such as federally funded programs and national nonprofit
organizations.
PMID- 28495043
TI - Setting Research Priorities for Kidney Cancer.
AB - Defining disease-specific research priorities in cancer can facilitate better
allocation of limited resources. Involving patients and caregivers as well as
expert clinicians in this process is of value. We undertook this approach for
kidney cancer as an example. The Kidney Cancer Research Network of Canada
sponsored a collaborative consensus-based priority-setting partnership that
identified ten research priorities in the management of kidney cancer. These are
discussed in the context of current initiatives and gaps in knowledge.
PMID- 28495045
TI - Deterioration in gait and functional ambulation in children and adolescents with
Charcot-Marie-Tooth disease over 12 months.
AB - Children and adolescents with Charcot-Marie-Tooth disease (CMT) report problems
with gait. Little is known about gait changes over time in children with this
degenerative disease. This prospective longitudinal study investigated change in
spatio-temporal gait parameters and functional ambulation. Two assessments were
conducted 12 months apart. Assessments included: barefoot gait on an electronic
walkway; functional ambulation with a six minute walk test and the Functional
Mobility Scale; and disease severity with the CMT Pediatric Scale. Gait and
strength data were normalised to body anthropometrics. Twenty-seven children
(mean age 12.2, SD 3.7 years) with various CMT subtypes (CMT1A 52%) were
evaluated. Over 12 months, normalised variables of gait speed, stride length and
six minute walk distance significantly decreased. The CMT Pediatric Scale
increased 0.7 points, indicating marginal but not significant worsening of
disease; notably calf strength decreased significantly over 12 months. Baseline
maximum ankle dorsiflexion angle, gastrocnemius and hamstrings length, and calf
strength correlated with decline in gait speed, with maximum ankle dorsiflexion
angle as the strongest predictor. Deterioration over one year in normalised
variables of gait speed, stride length and distance walked in six minutes are
indicators of functional decline and disease progression in children and
adolescents with CMT.
PMID- 28495044
TI - Cognitive and academic outcomes in long-term survivors of infantile-onset Pompe
disease: A longitudinal follow-up.
AB - This study examines the long-term cognitive and academic outcomes of 11
individuals with infantile onset Pompe disease (IOPD) (median age=11years,
1month, range=5years, 6months through 17years of age) treated with enzyme
replacement therapy from an early age. All participants (7 males, 4 females) were
administered individual intelligence tests (Wechsler or Leiter scales or both), a
measure of their academic skill levels (Woodcock-Johnson Tests of Achievement),
and a screening measure of visual-motor integration ability (Beery-Buktenica).
Consistent with our earlier findings, median IQ scores for the entire group on
the Wechsler (median=84) and Leiter (median=92) scales continue to fall at the
lower end of the average range compared to same-aged peers. The median scores for
the group on a measure of visual-motor integration (median=76), visual perception
(median=74) and motor coordination (median=60) were below average. Two distinct
subgroups emerged based on participants' average or below average performance on
the majority of academic subtests. Those participants with below average academic
skills (n=6) demonstrated average nonverbal cognitive abilities on the Leiter,
but had weaknesses in speech and language skills and greater medical involvement.
Their profiles were more consistent with a learning disability diagnosis than an
intellectual disability. Two of these participants showed a significant decline
(15 and 23 points, respectively) on repeated Wechsler scales, but one continued
to earn average scores on the Leiter scales where the verbal and motor demands
are minimal. Participants with average academic skills (n=5) demonstrated average
cognitive abilities (verbal and nonverbal) on the Wechsler scales and less
medical involvement. Their speech and language skills appeared to be more intact.
However, both groups earned below average median scores on the Beery-Buktenica
motor coordination task. This study highlights the importance of using
appropriate tests to capture both verbal and nonverbal abilities, considering
each individual's motor skills, speech and language abilities, hearing status and
native language. This will allow for a more accurate assessment of whether there
is a learning disability or an intellectual disability. Long-term outcomes may be
related to the stability of an individual's expressive and/or receptive language
abilities over time. Changes in the speech and language domain may account for
the decline in IQ observed in some IOPD long-term survivors, reflecting a
learning disability rather than a decline in overall cognition or an intellectual
disability. These observations, in conjunction with neuroimaging, will further
our understanding of the neurocognitive profile of long-term IOPD survivors.
PMID- 28495046
TI - Transient neonatal myasthenia gravis due to a mother with ocular onset of anti
muscle specific kinase myasthenia gravis.
AB - We describe a 27-year-old pregnant female with new onset of conjugate gaze
deficit during the third trimester of pregnancy. Repetitive nerve stimulation
tests, neostigmine tests, and acetylcholine receptor antibody assays were all
negative. The patient delivered a normal healthy baby at a local clinic via
cesarean section. The baby became hypotonic and had respiratory failure several
minutes after birth. The result of acetylcholine receptor antibody was negative
in the neonate. The neonate became healthy spontaneously and was extubated after
21 days of ventilation care. Two months after delivery, the mother developed
ptosis and generalized symptoms and subsequent workup revealed she was muscle
specific kinase (MuSK) antibody positive. The neonate was presumed to have an
anti-MuSK-mediated transient neonatal myasthenia gravis. Although MuSK antibody
testing is rarely indicated in ocular myasthenia gravis, MuSK antibody testing is
necessary in pregnant women who are presumed ocular myasthenia gravis to warn
occurrence of transient neonatal myasthenia gravis.
PMID- 28495047
TI - Similar clinical, pathological, and genetic features in Chinese patients with
autosomal recessive and dominant Charcot-Marie-Tooth disease type 2K.
AB - Mutations in the ganglioside-induced differentiation-associated protein 1 gene
(GDAP1) cause rare subtypes of Charcot-Marie-Tooth disease (CMT2K and CMT4A).
CMT2K is an axonal neuropathy while CMT4A is a demyelinating type. In a series of
169 Chinese CMT patients (79 CMT1, 52 CMT2 and 38 unclassified), four unrelated
patients (2.37%) were identified with GDAP1 mutations, including two with
autosomal recessive CMT2K (AR-CMT2K) and two dominant CMT2K (AD-CMT2K). All
patients had disease onset before 5 years of age, and presented with muscle
weakness, atrophy, and mild sensory disturbance in distal limbs. Motor nerve
conduction velocities of the median nerve were within normal ranges, and compound
muscle action potential ranged from 1.5 to 3.8 mV. Sural nerve biopsy revealed
loss of large myelinated fibers with regeneration clusters and a few onion bulbs.
Electron microscopy showed mitochondrial aggregation in both axons and Schwann
cells, and neurofilament accumulation in giant unmyelinated fibers. The p.H256R
mutation was found in all patients with GDAP1 compound heterozygous mutations,
suggesting that it might be a common mutation in Chinese patients. This study
observed no difference in the disease onset, phenotype severity,
electrophysiological findings, or pathological changes between AR-CMT2K and AD
CMT2K patients.
PMID- 28495049
TI - Selective or predominant triceps muscle weakness in African-American patients
with myasthenia gravis.
AB - Myasthenia gravis (MG) can lead to weakness in different patterns of muscle
groups. Limb muscle weakness is most typically seen in a limb girdle pattern,
although variants exist. In the current study, we aimed to describe a unique MG
phenotype consisting of selective or predominant triceps muscle weakness. We
performed a retrospective review of MG patients who developed focal or
predominant triceps muscle weakness between 2006 and 2016. The clinical,
electrophysiological and serological characteristics of these patients were
examined. 8 MG patients were identified, including 7 males, all of whom were
African-American. Two patients underwent muscle biopsy, and one patient underwent
cervical spine decompression surgery. All showed significant improvement
following immunosuppressive treatment, although one patient experienced a relapse
of muscle weakness. This case series highlights a relatively uncommon MG clinical
phenotype of selective triceps muscle weakness, mainly in African-American males,
in line with previous literature. Familiarity with this phenotype is important in
order to facilitate diagnosis and appropriate treatment for this group, and avoid
unnecessary investigations or treatments.
PMID- 28495048
TI - HLA and age of onset in myasthenia gravis.
AB - The aetiology of MG is unknown, but both genetic and environmental factors are
important. Over the years association of MG with Human Leucocyte Antigens (HLA)
has been described in different populations. We investigated a possible
association between HLA-DRB1 alleles and age of onset in MG. One hundred and
fourteen MG patients (82 females) and 282 control individuals (CP) were studied.
Patients were classified according to the age of onset (early-onset <50, n = 74
and late-onset >= 50, n = 20). Patients with thymoma (n = 20) were analyzed
separately. HLA-DRB1 and HLA-B*08 genotyping was performed using PCR-SSP
methodology. HLA-DRB1*03 allele was overrepresented in the global MG. When the
early-onset subgroup was considered, this association became even stronger.
Regarding the late-onset subgroup, the frequency of HLA-DRB1*01 allele was higher
than in the CP. For the thymoma subgroup, the HLA-DRB1*10 allele frequency was
significantly higher when compared to the CP. These results have shown a strong
association of HLA-DRB1*03 with MG, especially for EOMG also in our population.
HLA-DRB1*01 was associated to LOMG suggesting that is a susceptibility factor for
this subgroup of the disease. This study confirms a different genetic background
of MG subgroups regarding age of onset.
PMID- 28495050
TI - Deep intronic variants introduce DMD pseudoexon in patient with muscular
dystrophy.
AB - Dystrophinopathies are X-linked muscle diseases caused by mutations in the large
DMD gene. The most common mutations are detected by standard diagnostic
techniques. However, some patients remain without detectable mutation, most
likely due to changes in the non-coding sequence. We report on a boy with
complete absence of dystrophin in muscle biopsy but no causative mutation
according to standard diagnostics. To search for deep intronic variations (DIV)
in the DMD gene we isolated mRNA from muscle tissue and amplified overlapping
cDNA fragments using RT-PCR. One cDNA product revealed an augmented fragment size
showing an insertion of 77 bp between the exons 7 and 8 by sequencing. We
sequenced the flanking sequences of gDNA and found two hemizygous single
nucleotide variants (c.650-39575 A>C and c.650-39498 A>G) surrounding the
inserted fragment. Both variants create cryptic splice sites which initiate the
formation of a pseudoexon that produces a frameshift in the DMD gene.
PMID- 28495051
TI - Bone histological correlates of soaring and high-frequency flapping flight in the
furculae of birds.
AB - The furcula is a specialized bone in birds involved in flight function. Its
morphology has been shown to reflect different flight styles from soaring/gliding
birds, subaqueous flight to high-frequency flapping flyers. The strain
experienced by furculae can vary depending on flight type. Bone remodeling is a
response to damage incurred from different strain magnitudes and types. In this
study, we tested whether a bone microstructural feature, namely Haversian bone
density, differs in birds with different flight styles, and reassessed previous
work using phylogenetic comparative methods that assume an evolutionary model
with additional taxa. We show that soaring birds have higher Haversian bone
densities than birds with a flapping style of flight. This result is probably
linked to the fact that the furculae of soaring birds provide less protraction
force and more depression force than furculae of birds showing other kinds of
flight. The whole bone area is another explanatory factor, which confirms the
fact that size is an important consideration in Haversian bone development. All
birds, however, display Haversian bone development in their furculae, and other
factors like age could be affecting the response of Haversian bone development.
PMID- 28495052
TI - Geographic variation in factors that influence timing of moult and breeding in
waterfowl.
AB - Waterfowl flight-feather moult is expected to occur when energy is not needed for
breeding and when a suitable safe habitat is available. Flight-feather regrowth
is an energetically costly stage in the annual cycle of waterfowls. In this
study, we tested the hypothesis that moult will coincide with the time of year
when food and aquatic habitats are most abundant. We investigated how the timing
of rainfall relates to the timing of breeding and flight-feather moult in five
common southern African waterfowl at two sites in South Africa with opposite
rainfall regimes (one summer, one winter). We then incorporated published data to
compare and contrast the relative timing of breeding and moult in southern
hemisphere (southern African and Australian) waterfowl with northern hemisphere
(European and North American) species. Our results showed that southern African
waterfowl breed in the wet season and moult during the dry season. Tadorna cana
was an exception, breeding in the dry season and moulting during the wet season
in the summer-rainfall area. There was also a long lag period between peak
breeding and peak moult in southern hemisphere waterfowl species, the longest lag
being that of birds in the summer-rainfall area. By comparison, northern
hemisphere waterfowl species breed and moult during the warm season, with a
shorter lag period between peak breeding and peak moult compared to southern
hemisphere species. We concluded that waterfowl in southern Africa (with the
exception of T. cana), southeast Australia, Europe and North America time their
breeding period to coincide with peaks in the availability of both food and
breeding sites. Northern hemisphere species moult where chances of predation are
low, when temperatures are warm, and before food and aquatic habitats approach
their winter minima. By contrast, southern hemisphere waterfowl delay the onset
of moult until the dry season, opting to moult when both food and aquatic
moulting habitats are scarce.
PMID- 28495053
TI - Evaluation of Preoperative Aspartate Transaminase/Alanine Transaminase Ratio as
an Independent Predictive Biomarker in Patients With Metastatic Renal Cell
Carcinoma Undergoing Cytoreductive Nephrectomy: A Propensity Score Matching
Study.
AB - BACKGROUND: The usefulness of the aspartate transaminase (AST)/alanine
transaminase (ALT) ratio (De Ritis ratio) as a predictive biomarker for patients
with metastatic renal cell carcinoma (mRCC) undergoing cytoreductive nephrectomy
(CN) remains unclear. PATIENTS AND METHODS: The data from 118 patients were
retrospectively evaluated. The endpoints were cancer-specific survival (CSS) and
overall survival (OS) after CN. We compared these according to the AST/ALT ratio
before and after 1:1 propensity score matching. The independent predictors for
CSS and OS were also analyzed. RESULTS: The area under the receiver operating
characteristic curve was 0.603. The maximum Youden index indicated that the
cutoff value for the AST/ALT ratio was 1.24. Before matching, a high AST/ALT
ratio was significantly associated with inferior CSS and OS (P < .05 for all).
After matching, 34 patients each were allocated to the high and low AST/ALT ratio
groups. In the matched cohort, CSS and OS tended to be lower in the high AST/ALT
ratio group, although the results were not statistically significant (median CSS,
18.4 months vs. not reached, P = .121; OS, 18.4 months vs. not reached, P =
.0957). Furthermore, multivariate analyses revealed that the AST/ALT ratio was an
independent predictor for CSS and OS (CSS hazard ratio, 2.17, P = .0472; OS
hazard ratio, 2.30, P = .0258). CONCLUSION: The preoperative AST/ALT ratio can be
an effective predictive biomarker for CSS and OS in patients with mRCC.
PMID- 28495054
TI - Phasic availability of terminal electron acceptor on oxygen reduction reaction in
microbial fuel cell.
AB - Oxygen-reduction reactions (ORR) plays a pivotal role in determining microbial
fuel cells (MFC) performance. In this study, an attempt to determine the
influence of the phasic availability of terminal electron acceptor (TEA) on ORR
was made. Two MFCs operated with dissolved oxygen (MFC-DC) and air (MFC-SC) as
TEA were constructed and analyzed in continuous mode under open and closed
circuit conditions. The bio-electrochemical analysis showed a marked influence of
dissolved oxygen resulting in a maximum power density with MFC-DC (769mW/m2)
compared to MFC-SC (684mW/m2). The availability of O2 in dissolved phase has
lowered the activation losses during the MFC operation as a result of effective
ORR. The cyclic voltammetry analysis revealed the TEA dependent biocatalyst
activity of NADH and cytochrome complex which enabled electron transfer kinetics
and improved substrate utilization. Finally, the study evidenced the critical
role of TEA phasic availability to regulate the bio-electrogenic and substrate
degradation potential in MFC.
PMID- 28495055
TI - Production and characterization of chars from cherry pulp via pyrolysis.
AB - Pyrolysis is an eco-friendly process to achieve valuable products like bio-oil,
char and gases. In the last decades, biochar production from pyrolysis of a wide
variety of industrial and agricultural wastes become popular, which can be
utilized as adsorbent instead of the expensive activated carbons. In this study,
cherry pulp was pyrolyzed in a fixed bed tubular reactor at five different
temperatures (400, 500,550, 600 and 700 degrees C) and three different heating
rates (10, 100 and 200 degrees C/min) to obtain biochar. Proximate, ultimate,
nitrogen adsorption/desorption isotherms, scanning electron microscopy,
thermogravimetric analysis, x-ray fluorescence, x-ray diffraction, and Fourier
transform infrared spectroscopy were performed on cherry pulp and its chars to
examine the chemical alterations after the pyrolysis process. Biochar yields were
decreased with increasing pyrolysis temperature and heating rate, based on
experimental results. Porous biochars are carbon rich and includes high potassium
content. The aromaticity of biochars increased and O/C mass ratio reduced with an
increase in the pyrolysis temperature as a result of the development of compact
aromatic structure in char. Pyrolysis provides a promising conversion procedure
for the production of high energy density char which has promising applications
in existing coal-fired boilers without any upgrading.
PMID- 28495056
TI - A novel minimally invasive near-infrared thoracoscopic localization technique of
small pulmonary nodules: A phase I feasibility trial.
AB - OBJECTIVES: Localization and resection of nonvisible, nonpalpable pulmonary
nodules during video-assisted thoracoscopic surgery are challenging. Our study
was to determine the feasibility and safety of indocyanine green fluorescence
localization and resection of small nodules using a near-infrared fluorescence
thoracoscope. METHODS: Twenty patients with undiagnosed peripheral nodules
smaller than 3 cm scheduled for computed tomography-guided microcoil placement
followed by video-assisted thoracoscopic surgery wedge resection were enrolled.
After microcoil deployment, 100 to 150 MUL of diluted indocyanine green was
injected percutaneously near the nodule. The nodule initially was localized
solely by using a near-infrared thoracoscope to visualize indocyanine green
fluorescence. Thoracoscopic instruments were used to determine the staple line.
Wedge resection was performed after confirmation of the location of the microcoil
using fluoroscopy. RESULTS: Twenty patients underwent near-infrared, image
guided, video-assisted thoracoscopic surgery resection. The median computed
tomography tumor size was 1.2 cm. The median depth from the pleural surface was
1.4 cm (range, 0.2-4.8 cm). The median computed tomography-guided intervention
time was 35 minutes, and video-assisted thoracoscopic surgery procedural time was
54 minutes. Indocyanine green fluorescence was clearly identified in 18 of 20
patients (90%). The surgical margins were all negative on final pathology without
the need for additional resection. The final diagnoses included 18 primary lung
cancers, 1 metastatic lung cancer, and 1 benign lung tumor. CONCLUSIONS: Computed
tomography-guided percutaneous indocyanine green injection and intraoperative
near-infrared localization of small nodules are safe and feasible. These offer
surgeons the ease of localization through direct indocyanine green fluorescence
imaging without the use of fluoroscopy and may be a complementary technique to
preoperative microcoil placement for nonvisible, nonpalpable intrapulmonary
nodules.
PMID- 28495057
TI - Cardiac surgery training in Canada: Current state and future perspectives.
PMID- 28495058
TI - miRNA profiling of primary lung and head and neck squamous cell carcinomas:
Addressing a diagnostic dilemma.
AB - OBJECTIVE: To determine whether microRNA (miRNA) profiling of primary lung and
head and neck squamous cell carcinomas could be useful to identify a specific
miRNA signature that can be used to further discriminate between primary lung
squamous carcinomas and metastatic lesions in patients with a history of head and
neck squamous cell cancer. METHODS: Specimens of resected primary head and neck
and lung squamous cell carcinomas were obtained from formalin-fixed, paraffin
embedded blocks. Paraffin blocks were sectioned and deparaffinized, and total RNA
was isolated and profiled. Quantitative polymerase chain reaction was performed
to verify array results. RESULTS: Twelve head and neck and 16 lung squamous cell
carcinoma samples met quality control metrics and were included for analysis.
Forty-eight miRNAs were differentially expressed (P < .05) between the 2 groups.
Of these, 30 were also significantly associated (q < .25) with tumor type in 2
independent sets of primary head and neck and lung squamous carcinomas profiled
by The Cancer Genome Atlas consortium, including miR-34a and miR-10a. The ratio
of miR-10a and miR-10b was especially predictive of primary cancer site in all 3
data sets, with area under the (receiver operating characteristics) curve values
ranging from 0.922 to 0.982. Quantitative polymerase chain reaction confirmed the
association of miR-34a expression and the miR-10:miR-10b ratio with tumor type.
CONCLUSIONS: MicroRNA expression may be useful for discriminating between head
and neck and lung squamous cell carcinomas, including miR-34a and the miR-10a:miR
10b ratio. This differentiation has clinical importance because it could help
determine the appropriate therapeutic approach.
PMID- 28495059
TI - Bicuspid aortic valve aortopathy is not cancer.
PMID- 28495060
TI - Hot nodules and histologic features: The emerging story of stage IA lung
adenocarcinoma.
PMID- 28495061
TI - High-risk cardiac surgery as an alternative to transplant or mechanical support
in patients with end-stage heart failure.
AB - OBJECTIVE: Although the results of cardiac surgery in patients with poor left
ventricular function have been widely published, the outcomes in patients with
end-stage heart failure who meet criteria for advanced therapies are not well
investigated. As access to transplantation and ventricular assist device therapy
remains limited, we explored the possibility of conventional surgery as an
alternative option for highly selected patients with end-stage heart failure.
METHODS: We identified patients with left ventricular ejection fraction <20% and
VO2 max <14 mL/min/m2, who were initially referred for advanced therapies but
were instead offered a conventional procedure from 2002 to 2012. We examined the
short- and midterm outcomes and compared survival with that after our advanced
therapies in the same era. RESULTS: A total of 133 patients were identified; 68
were deemed to be transplant-eligible, whereas 65 were transplant-ineligible.
Seventy-nine percent were in New York Heart Association class III/IV. In-hospital
mortality was 12%. Actuarial survival at 5 and 10 years was 72% +/- 4% and 39% +/
8%, respectively. Nonischemic etiology was identified as a predictor of late
mortality. In the propensity-adjusted model, our transplant-eligible patients had
comparable long-term survival to our transplantation patients (HR 1.48 [95%
confidence interval, 0.66-3.2], P = .34), whereas the survival in our transplant
ineligible subset was comparable to the survival after our left ventricular
assist device therapy (HR 0.49 [95% confidence interval, 0.16-1.50], P = .21).
CONCLUSIONS: Despite high perioperative risk, the midterm survival after
conventional surgery in patients eligible for advanced therapies seems to be
acceptable and may be an alternative option for highly selected patients with end
stage heart failure.
PMID- 28495062
TI - Discussion.
PMID- 28495064
TI - Discussion.
PMID- 28495063
TI - Topical amiodarone during cardiac surgery: Does epicardial application of
amiodarone prevent postoperative atrial fibrillation?
AB - OBJECTIVES: Atrial fibrillation (AF) is a common complication after cardiac
surgery. Topical amiodarone on the epicardium may help prevent postoperative AF
while avoiding the side effects of its systemic administration. The purpose of
this study was to evaluate the all-comer strategy of epicardial amiodarone
application for the prevention of postoperative AF. METHODS: A retrospective
observational study was performed that evaluated the incidence of new-onset AF in
a consecutive series of cardiac surgery patients who were treated with either no
amiodarone (historical control, n = 100), epicardial application of amiodarone
mixed in a topical hydrogel (n = 50), or epicardial application of an amiodarone
soaked sealant patch (n = 50). Perioperative data were compared between the 3
groups, with all patients receiving continuous postoperative telemetry to monitor
for new-onset AF. RESULTS: The cohort consisted of 200 cardiac surgery patients
(coronary bypass 82%, valve surgery 24%) who had no history of AF (mean age 71.0
years, 28% female). Among the 3 groups, the incidence of postoperative AF did not
significantly differ, with 29 of 100 (29%) patients in the historical control
group having new AF, compared with 18 of 50 (36%) in the amiodarone-hydrogel
group, and 18 of 50 (36%) in the amiodarone-patch group (P = .56). The results
did not differ when the analysis was restricted to coronary bypass patients only
(n = 142, 27% vs 38% vs 32%, no-amiodarone vs amiodarone-hydrogel vs amiodarone
patch, respectively, P = .56). In multivariate logistic regression analysis, only
older age (P = .001) was significantly associated with new-onset AF, but the use
of topical amiodarone was not. CONCLUSIONS: Routine epicardial application of
topical amiodarone was not associated with a reduction in the incidence of new
onset postoperative AF in this observational study of older patients, leading us
to question its role in contemporary cardiac surgical practice.
PMID- 28495065
TI - The miniaturized pediatric continuous-flow device: Preclinical assessment in the
chronic sheep model.
AB - BACKGROUND: The Infant Jarvik 2015 is an implantable axial-flow ventricular
assist device (VAD) that has undergone the major evolutionary design
modifications to improve hemocompatibility. This study was conducted in
anticipation of data submission to the US Food and Drug Administration to obtain
Investigational Device Exemption approval. METHODS: The VAD was implanted via a
left thoracotomy in Barbado sheep (n = 10, 26 (19-34] kg). Anticoagulation was
maintained with coumadin, with a target international normalized ratio of greater
than the individual sheep's baseline values. The VAD was managed at the highest
possible speed as clinically tolerable. Complete necropsy was performed at the
end of the study. RESULTS: There were 2 early mortalities: tension pneumothorax
(n = 1) and shower emboli of the fragmented myocardium (n = 1). The remaining 8
sheep (2 with 30-day and 6 with 60-day protocols) completed the anticipated study
duration in excellent condition, with the 6 completing 60-day sheep showing
appropriate weight gain during support. There were no signs of clinically
significant hemolysis, with the final plasma-free hemoglobin of 2 (1-17) mg/dL.
Necropsy showed old renal infarction in 7 sheep. Although thromboembolism can be
the potential etiology, given the mild anticoagulation regimen, other sources of
emboli were identified in 2 sheep (graft coating material and fragmented
myocardium). Flow study demonstrated favorable increase in flow (up to 3.0 L/min)
in proportion to change in pump speed. CONCLUSIONS: This study has demonstrated
that the Infant Jarvik 2015 VAD is capable of maintaining its functionality for
an extended period of time with minimal hemolysis.
PMID- 28495066
TI - Salvage pulmonary resection after stereotactic body radiotherapy: A feasible and
safe option for local failure in selected patients.
AB - OBJECTIVE: For inoperable patients with pulmonary malignancy, stereotactic body
radiotherapy is a reasonable therapeutic option. Despite good early tumor
control, local failure occurs in up to 10% of patients by 3 years. Because
management of local recurrence after stereotactic body radiotherapy is unclear,
we evaluated use of surgery as a salvage option. METHODS: A retrospective review
was conducted of consecutive patients from a single institution who underwent
salvage resection of primary and metastatic pulmonary malignancies previously
treated with stereotactic body radiotherapy. In addition, a literature search was
conducted to identify previous reports of pulmonary resection for local
stereotactic body radiotherapy failures, to allow cumulative analyses with
previously published cases. RESULTS: A total of 21 patients met inclusion
criteria. The median time between stereotactic body radiotherapy and salvage
surgery was 16.2 months (range, 6.4-71.5). Postoperative complications occurred
in 7 patients (18.9%), in whom atrial arrhythmias and prolonged air leaks (>5
days) were most frequent (n = 2 each, 5.4%). There was no local recurrence after
salvage surgery. Distant failure occurred in 5 of 21 patients (23.8%) at a median
of 36.2 months, and median disease-free survival was 19.2 months. The 30- and 90
day mortality was 4.8% (1 patient). Cumulative analysis included 37 patients from
4 institutions and comprised 26 (78.8%) primary non-small cell lung cancers and
11 (29.7%) lung metastases. Median overall survival after salvage surgery was
46.9 months, and 3-year survival was 71.8%. CONCLUSIONS: After local failure of
stereotactic body radiotherapy, salvage resection remains a viable option for
operable patients, with acceptable morbidity and survival. As use of stereotactic
body radiotherapy continues to expand, further studies to evaluate the optimal
management for local failure are needed.
PMID- 28495067
TI - Discussion.
PMID- 28495068
TI - Discussion.
PMID- 28495069
TI - The importance of arch geometry after Norwood reconstruction.
PMID- 28495071
TI - Perioperative and economic analysis of surgical treatments for benign prostatic
hyperplasia: A study of the French committee on LUT.
AB - PURPOSE: To evaluate perioperative cost related to surgical treatments of benign
prostatic obstruction (BPO): photoselective vaporization of the prostate (pvp),
holmium/thullium laser enucleation (HoLEP/ThuLEP), transurethral resection of the
prostate (TURP) and open prostatectomy (OP). MATERIAL AND METHODS: We
retrospectively collected data from 237 patients who consecutively underwent a
surgical treatment for BPH between January 2012 and June 2013 at nine
institutions in France. An economic simulation model was constructed to estimate
the cost of hospitalization related to surgical procedure from the hospital
perspective and a cost minimization analysis was performed. RESULTS: TURP, OP,
HoLEP/ThuLEP and PVP were performed in 99 (42%), 23 (10%), 64 (27%) and 51 (21%)
patients, respectively. For men with prostate size<80mL: mean operative time was
shorter with mTURP and PVP than HoLEP/thuLEP (P<0.001); Mean postoperative length
of stay were 1.9, 3 vs. 3.4 days, for HoLEP/Thulep, PVP and TURP respectively
(P=0.006); Costs of first hospitalization were comparable between HoLEP/ThuLEP
and TURP but higher with PVP (P<0.001). For men with prostate size>=80mL:
Compared to PVP and HoLEP/ThuLEP, OP was associated with shorter operative time
(P<0.001) but longer length of stay (2.4, 4.2 vs. 7.8 days, respectively,
P<0.0001); Costs of first hospitalization were significantly higher with OP than
HoLEP/ThuLEP or PVP (P<0.001). CONCLUSIONS: PVP and HoLEP/ThuLEP were associated
with a shorter LOS than TURP and OP. This benefit suggests these procedures could
be more cost effective than OP, but still not cheaper alternatives to TURP. LEVEL
OF EVIDENCE: 5.
PMID- 28495072
TI - Reprint of "Application of next generation sequencing in clinical microbiology
and infection prevention".
AB - Current molecular diagnostics of human pathogens provide limited information that
is often not sufficient for outbreak and transmission investigation. Next
generation sequencing (NGS) determines the DNA sequence of a complete bacterial
genome in a single sequence run, and from these data, information on resistance
and virulence, as well as information for typing is obtained, useful for outbreak
investigation. The obtained genome data can be further used for the development
of an outbreak-specific screening test. In this review, a general introduction to
NGS is presented, including the library preparation and the major characteristics
of the most common NGS platforms, such as the MiSeq (Illumina) and the Ion PGMTM
(ThermoFisher). An overview of the software used for NGS data analyses used at
the medical microbiology diagnostic laboratory in the University Medical Center
Groningen in The Netherlands is given. Furthermore, applications of NGS in the
clinical setting are described, such as outbreak management, molecular case
finding, characterization and surveillance of pathogens, rapid identification of
bacteria using the 16S-23S rRNA region, taxonomy, metagenomics approaches on
clinical samples, and the determination of the transmission of zoonotic micro
organisms from animals to humans. Finally, we share our vision on the use of NGS
in personalised microbiology in the near future, pointing out specific
requirements.
PMID- 28495070
TI - Is social support associated with post-transplant medication adherence and
outcomes? A systematic review and meta-analysis.
AB - Although social support is used to determine transplant eligibility, the
relationship between social support, medication adherence, and survival among
transplant recipients remains unclear. We estimated the relationship between
social support and post-transplant medication adherence and outcomes using 10
electronic databases from inception to January 2016. Study quality was assessed
and all review stages were conducted independently by 2 reviewers. Systematic
review and meta-analysis were conducted. Thirty-two studies (9102 participants)
met inclusion criteria: 21 assessed medication adherence (5197 participants), and
13 assessed clinical outcomes (3905 participants). Among high quality studies,
neither social support nor marital status was predictive of medication adherence
or post-transplant outcomes. Social support was not associated with medication
adherence. It was associated with superior post-transplant outcomes, but the
relationship was not significant among high quality studies. Compared to
unmarried recipients, married recipients were more likely to adhere to medication
post-transplant, but this relationship was not significant among high quality
studies. Marital status was not significantly associated with transplant success.
Social support is weakly and inconsistently associated with post-transplant
adherence and outcomes. Larger prospective studies using consistent and validated
measures are needed to justify the use of inadequate social support as a
contraindication to transplantation.
PMID- 28495074
TI - The Rationale for GesEPOC in Our Environment.
PMID- 28495073
TI - Expert Statement on the Single-Agent Use of Inhaled Bronchodilator in the
Treatment of Stable Mild-Moderate Chronic Obstructive Pulmonary Disease.
AB - OBJECTIVE: To describe the evidence- and experience-based expert consensus on the
use of single-agent bronchodilators in patients with stable mild-moderate chronic
obstructive pulmonary disease (COPD). METHODS: Using Delphi methodology, a panel
of 7 respiratory medicine experts was established, who, in the first nominal
group meeting defined the scope, users, and document sections. The panel drew up
14 questions on the use of single-agent bronchodilators in patients with mild
moderate stable COPD to be answered with a systematic review of the literature.
The results of the review were discussed in a second nominal group meeting and 17
statements were generated. Agreement/disagreement with the statements was tested
among16 different experts including respiratory medicine experts and primary care
physicians. Statements were scored from1 (total disagreement) to10 (total
agreement). Agreement was considered if at least 70% voted >=7. The level of
evidence and grade of recommendation of the systematic literature review was
assessed using the Oxford Centre for Evidence-based Medicine levels. RESULTS: A
total of 12 of the 17 statements were selected. Specific statements were
generated on different profiles of patients with stable mild-moderate COPD in
whom single-agent bronchodilators could be prescribed. CONCLUSIONS: These
statements on the use of single-agent bronchodilators might improve the outcomes
and prognosis of patients with stable mild-moderate COPD.
PMID- 28495075
TI - Relationship Between Chronic Obstructive Pulmonary Disease and Air Pollutants
Depending on the Origin and Trajectory of Air Masses in the North of Spain.
AB - OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a common respiratory
condition and one of the leading causes of death. Our aim was to analyze the
association between emergency room visits due to this disease and meteorological
variables and atmospheric contaminant levels in Santander, depending on the
origin and trajectory of air masses. METHODS: Data from emergency room visits at
Hospital Marques de Valdecilla were collected on a daily basis during an 8-year
period. Data on concentrations of the main atmospheric pollutants and
meteorological variables were also recorded.Retrotrajectories leading to
Santander at a height of1,500 meters above sea level were then calculated.
Finally, a correlation model was produced to evaluate the effect of the
contaminants on emergency visitsdue to COPD. RESULTS: There is a direct
association between PM 10 levels and the number of visits to the emergency room
due to COPD. For every 10MUg/m3 increase in pollutantlevels, emergency
visitsincrease by3.34% (p=0.00005), and thiseffect is enhanced in individualsover
74 years of age. This effect is heightened when PM10 levels depend on air masses
from the South and when air recirculation occurs. There is no association
betweenother pollutants and the number of visits to the emergency room.
CONCLUSIONS: Exposure to high levels of PM10 causes exacerbations in COPD
patients. By studying the atmospheric circulation pattern, we can predict whether
PM10 levels will be inappropriately high, and we can also obtain information
about the particle components.
PMID- 28495076
TI - Fungal Empyema: An Uncommon Entity With High Mortality.
PMID- 28495077
TI - Consensus on the Asthma-COPD Overlap Syndrome (ACOS) Between the Spanish COPD
Guidelines (GesEPOC) and the Spanish Guidelines on the Management of Asthma
(GEMA).
AB - Following a proposal by the Spanish Society of Pulmonology and Thoracic Surgery
(SEPAR), sponsor of the Spanish COPD Guidelines (GesEPOC) and the Spanish
Guidelines on the Management of Asthma (GEMA), authors of both papers have
unified the criteria for the diagnosis of asthma-COPD overlap syndrome (ACOS).
This consensus defines ACOS as the presence in a given patient of three elements:
significant smoking exposure, chronic airflow limitation and asthma. Diagnosis is
confirmed when a patient (35years of age or older), smoker or ex-smoker of more
than 10 pack-years, presents airflow limitation (post-bronchodilator
FEV1/FVC<0.7) that persists after treatment with bronchodilators and inhaled
corticosteroids (even after systemic corticosteroids in selected cases), and an
objective current diagnosis of asthma (according to GEMA criteria). In cases in
which the diagnosis of asthma cannot be demonstrated, marked positive results on
a bronchodilator test (FEV1>=15% and >=400mL) or elevated blood eosinophil count
(>=300eosinophils/MUL) will also be diagnostic of ACOS. The opinion of another 33
experts who had not participated in the consensus was sought using a modified
Delphi survey. Up to 80% of respondents gave a very positive opinion of the
consensus, and declared that it was better than other previous proposals. The
GesEPOC-GEMA consensus on ACOS provides a unique perspective of the diagnostic
problem, using a simple proposal and a pragmatic diagnostic algorithm that can be
applied at any healthcare level.
PMID- 28495078
TI - Favourable effect of early versus late start of enzyme replacement therapy on
plasma globotriaosylsphingosine levels in men with classical Fabry disease.
AB - BACKGROUND: The level of plasma globotriaosylsphingosine (lysoGb3) is an
indication of disease severity in Fabry disease (FD) and its decrease during
enzyme replacement therapy could be a reflection of treatment efficacy. Early
treatment of FD may improve clinical outcome, but data to support this hypothesis
are scarce. In this study we compared lysoGb3 decrease after ERT initiation in
men with classical FD who started ERT before the age of 25 (early-treatment) with
those who started later in life (late-treatment). METHODS: Treatment naive men
with classical FD from three centers of excellence in Europe were included.
Measurements of lysoGb3 levels by tandem mass spectroscopy and antibodies by an
inhibitory assay were performed in a single laboratory. Results were adjusted for
lysoGb3 at baseline, first ERT (i.e. agalsidase alfa or beta) and the average ERT
dose. RESULTS: 85 patients were included, 21 in the early-treatment and 64 in the
late-treatment group. LysoGb3 level at baseline was not different between the two
groups (112 vs 114nmol/L, p=0.92). The adjusted odds ratio for reaching a lysoGb3
level<20nmol/L was 7.38 for the early-treatment versus late-treatment group (95%
CI: 1.91-34.04, p=0.006). The adjusted lysoGb3 levels one year after ERT
initiation was 12.9nmol/L lower in the early-treatment (95% CI: -20.1--5.8,
p<0.001) compared to the late-treatment group. CONCLUSION: The current
retrospective cohort study shows that initiation of ERT at younger age in men
with classical Fabry disease results in a better biochemical response.
PMID- 28495079
TI - Behavior of macroporous vinyl silica and silica monolithic columns in high
pressure gas chromatography.
AB - 80% vinyltrimethoxysilane-based hybrid silica monoliths (80-VTMS), which have
been initially developed for separation in reversed-phase liquid chromatography,
have been investigated in high pressure gas chromatography separations (carrier
gas pressure up to 60bar) and compared to silica monolithic columns. The behavior
of both silica and 80-VTMS monolithic columns was investigated using helium,
nitrogen and carbon dioxide as carrier gas. The efficiency of 80-VTMS monolithic
columns was shown to vary differently than silica monolithic columns according to
the temperature and the carrier gas used. Carrier gas nature was a significant
parameter on the retention for both silica and vinyl columns in relation to its
adsorption onto the stationary phase in such high pressure conditions. The
comparison of retention and selectivity between 80-VTMS monoliths and silica was
performed under helium using the logarithm of the retention factor according to
the number of carbon atoms combined to Kovats indexes. The very good performances
of these columns were demonstrated, allowing the separation of 8 compounds in
less than 1min.
PMID- 28495080
TI - Determine equilibrium dissociation constant of drug-membrane receptor affinity
using the cell membrane chromatography relative standard method.
AB - The equilibrium dissociation constant (KD) of drug-membrane receptor affinity is
the basic parameter that reflects the strength of interaction. The cell membrane
chromatography (CMC) method is an effective technique to study the
characteristics of drug-membrane receptor affinity. In this study, the KD value
of CMC relative standard method for the determination of drug-membrane receptor
affinity was established to analyze the relative KD values of drugs binding to
the membrane receptors (Epidermal growth factor receptor and angiotensin II
receptor). The KD values obtained by the CMC relative standard method had a
strong correlation with those obtained by the frontal analysis method.
Additionally, the KD values obtained by CMC relative standard method correlated
with pharmacological activity of the drug being evaluated. The CMC relative
standard method is a convenient and effective method to evaluate drug-membrane
receptor affinity.
PMID- 28495082
TI - Synthesis and alpha-glucosidase inhibition activity of dihydroxy pyrrolidines.
AB - A new series of Deacetylsarmentamide A and B derivatives, amides and sulfonamides
of 3,4-dihydroxypyrrolidines as alpha-glucosidase inhibitors were designed and
synthesized. The biological screening test against alpha-glucosidase showed that
some of these compounds have the positive inhibitory activity against alpha
glucosidase. Saturated aliphatic amides were more potent than the olefinic
amides. Among all the compounds, 5o/6o having polar -NH2 group, 10f/11f having
polar -OH group on phenyl ring displayed 3-4-fold more potent than the standard
drugs. Acarbose, Voglibose and Miglitol were used as standard references. The
promising compounds 6i, 5o, 6o, 10a, 11a, 10f and 11f have been identified.
Molecular docking simulations were done for compounds to identify important
binding modes responsible for inhibition activity of alpha-glucosidase.
PMID- 28495081
TI - Phytochemical and cytotoxic studies on the leaves of Calotropis gigantea.
AB - A new lignan, 9'-methoxypinoresinol (1), and two new glycosylated 5
hydroxymethylfurfurals, calofurfuralside A (2), and calofurfuralside B (3),
together with nine known compounds (4-12) have been isolated from the active
fractions, CHCl3 (IC50, 0.32MUgmL-1) and EtOAc (IC50, 0.55MUgmL-1) fractions of
the leaves of Calotropis gigantea. Their structures were elucidated based on NMR
and MS data. Among the isolated compounds, compounds 1 and 9 exhibited potent
cytotoxicity against PANC-1 human pancreatic cancer cell line under the
normoglycemic condition with IC50 values of 3.7 and 3.3MUM, respectively. 9'
Methoxypinoresinol (1) significantly inhibited the colony formation of PANC-1
cells in a concentration-dependent manner.
PMID- 28495083
TI - Design and synthesis of potent inhibitors of the mono(ADP-ribosyl)transferase,
PARP14.
AB - A series of (Z)-4-(3-carbamoylphenylamino)-4-oxobut-2-enyl amides were
synthesized and tested for their ability to inhibit the mono-(ADP
ribosyl)transferase, PARP14 (a.k.a. BAL-2; ARTD-8). Two synthetic routes were
established for this series and several compounds were identified as sub
micromolar inhibitors of PARP14, the most potent of which was compound 4t,
IC50=160nM. Furthermore, profiling other members of this series identified
compounds with >20-fold selectivity over PARP5a/TNKS1, and modest selectivity
over PARP10, a closely related mono-(ADP-ribosyl)transferase.
PMID- 28495084
TI - Structural insight into the active site of mushroom tyrosinase using
phenylbenzoic acid derivatives.
AB - So far, many inhibitors of tyrosinase have been discovered for cosmetic and
clinical agents. However, the molecular mechanisms underlying the inhibition in
the active site of tyrosinase have not been well understood. To explore this
problem, we examined here the inhibitory effects of 4'-hydroxylation and
methoxylation of phenylbenzoic acid (PBA) isomers, which have a unique scaffold
to inhibit mushroom tyrosinase. The inhibitory effect of 3-PBA, which has the
most potent inhibitory activity among the isomers, was slightly decreased by 4'
hydroxylation and further decreased by 4'-methoxylation against mushroom
tyrosinase. Surprisingly, 4'-hydroxylation but not methoxylation of 2-PBA
appeared inhibitory activity. On the other hand, both 4'-hydroxylation and
methoxylation of 4-PBA increased the inhibitory activity against mushroom
tyrosinase. In silico docking analyses using the crystallographic structure of
mushroom tyrosinase indicated that the carboxylic acid or 4'-hydroxyl group of
PBA derivatives could chelate with cupric ions in the active site of mushroom
tyrosinase, and that the interactions of Asn260 and Phe264 in the active site
with the adequate-angled biphenyl group are involved in the inhibitory activities
of the modified PBAs, by parallel and T-shaped pi-pi interactions, respectively.
Furthermore, Arg268 could fix the angle of the aromatic ring of Phe264, and
Val248 is supposed to interact with the inhibitors as a hydrophobic manner. These
results may enhance the structural insight into mushroom tyrosinase for the
creation of novel tyrosinase inhibitors.
PMID- 28495085
TI - Reevaluation of fenpropimorph as a sigma receptor ligand: Structure-affinity
relationship studies at human sigma1 receptors.
AB - Fenpropimorph (1) is considered a "super high-affinity" sigma1 receptor ligand
(Ki=0.005nM for guinea pig sigma1 receptors). Here, we examine the binding of 1
and several of its deconstructed analogs at human sigma1 (hsigma1) receptors. We
monitored their subtype selectivity by determining the binding affinity at sigma2
receptors. In addition, we validated an existing pharmacophore model at the
molecular level by conducting 3D molecular modeling studies, using the crystal
structure of hsigma1 receptors, and Hydrophatic INTeractions (HINT) analysis. Our
structure affinity relationship studies showed that 1 binds with lower affinity
at hsigma1 receptors (Ki=17.3nM) compared to guinea pig; moreover, we found that
none of the fenpropimorph methyl groups is important for its binding at hsigma1
receptors, nor is stereochemistry. For example, removal of all methyl groups as
seen in 4 resulted in an almost 5-fold higher affinity at hsigma1 receptors
compared to 1 and 350-fold selectivity versus sigma2 receptors. In addition,
although the O atom of the morpholine ring does not contribute to affinity at
hsigma1 receptors (and might even detract from it), it plays role in subtype
(sigma1 versus sigma2 receptor) selectivity.
PMID- 28495086
TI - Cell line studies and analytical measurements of three paclitaxel complex
variations.
AB - The copper(II) cation, sucrose, and hydroxychloroquine were complexed with the
chemotherapy agent paclitaxel and studied for medicinal activity. Data (GI50,
LD50) from single dose and five dose National Cancer Institute sixty cell line
panels are presented. Analytical measurements of different complexes were made
using Nuclear Magnetic Resonance (1H NMR), Matrix Assisted Laser Desorption
Ionization-Time of Flight-Mass Spectrometry (MALDI-TOF-MS) and Fourier Transform
Ion Cyclotron Resonance (FT-ICR). Molecular modeling is utilized to better
understand the impact that species could have on physical parameters associated
with Lipinski's Rule of Five, such as logP and TPSA. On average, Cu(II) and
hydroxychloroquine decreased GI50 values, while sucrose increased GI50 values of
paclitaxel.
PMID- 28495087
TI - Gemcitabine anti-proliferative activity significantly enhanced upon conjugation
with cell-penetrating peptides.
AB - Gemcitabine proven efficiency against a wide range of solid tumors and undergoes
deamination to its inactive uridine metabolite, which underlies its low
bioavailability, and tumour resistance was also associated with nucleoside
transporter alterations. Hence, we have conjugated gemcitabine to cell
penetrating peptides (CPP), in an effort to both mask its aniline moiety and
facilitate its delivery into cancer cells. Two CPP-drug conjugates have been
synthesized and studied regarding both the time-dependent kinetics of gemcitabine
release and their anti-proliferative activity on three different human cancer
cell lines. Results obtained reveal a dramatic increase in the anti-proliferative
activity of gemcitabine in vitro, upon conjugation with the CPPs. As such, CPP
gemcitabine conjugates emerge as promising leads for cancer therapy.
PMID- 28495088
TI - Fluorescence guided resection with 5-aminolevulinic acid of a pilomyxoid
astrocytoma of the third ventricle.
AB - Fluorescence-guided resection with 5-aminolevulinic acid has been shown to be
useful in the resection of certain brain tumors other than high grade gliomas,
facilitating the intraoperative differentiation of neoplastic tissue. The
technique enables the surgeon to ensure that no tumor fragments remain, thereby
achieving higher rates of complete resection. Tihan first described pilomyxoid
astrocytomas in 1999. They are currently classified as grade II astrocytoma
according to the WHO classification system and, because of their tendency to
recur and their dissemination through the cerebrospinal fluid pathways, they are
considered to be more aggressive than pilocytic astrocytoma. As a result,
management of these tumors must be more aggressive, always aiming for complete
macroscopic resection whenever possible. In this article, we present a case of
pilomyxoid astrocytoma of the third ventricle in which the use of fluorescence
guided resection with 5-ALA facilitated complete resection. Imaging tests
performed after five years revealed no signs of recurrence and no adjuvant
radiotherapy or chemotherapy was required. This article also comprises a review
of the literature concerning the characteristics and management of this tumor,
which was recently considered to be a different histopathological entity.
PMID- 28495089
TI - Simultaneous measurements of cations and anions using diffusive gradients in thin
films with a ZrO-Chelex mixed binding layer.
AB - A new method for the simultaneous measurements of eight cations [Fe(II), Mn(II),
Co(II), Ni(II), Cu(II), Zn(II), Cd(II), and Pb(II)] and eight oxyanions [P(V),
V(V), Cr(VI), As(III)/As(V), Se(VI), Mo(VI), Sb(V), and W(VI)] was established in
this study using the diffusive gradients in thin films (DGT) technique with an
improved ZrO-Chelex binding gel. The binding kinetics of each analyte in a mixed
solution indicated a rapid uptake on the ZrO-Chelex gel. The anions exhibited
slower absorption rates compared to the cations, which did not affect the DGT
uptake. Stable elution efficiencies for these cations and anions were obtained
based on a two-step extraction procedure using 1.0 M HNO3 for elution of the
cations followed by a mixed solution containing 0.2 M NaOH and 0.5 M H2O2 for
elution of the anions. Simultaneous measurements of the cations and anions with
the ZrO-Chelex DGT were validated in mixed solutions and found to be independent
of solution pH (5-9) and ionic strength (2-3 mM to 750 mM). The capacities of the
ZrO-Chelex DGT for single measurements of Fe(II), P(V), Cd(II), As(III), and
As(V) were determined at 99.5, 127.6, 301.2, 33.3, and 87.4 MUg cm-2. Except for
Se(VI) in seawater, accurate measurements of all of these cations and anions in
natural freshwater and seawater were obtained using the ZrO-Chelex DGT. The
performance of this technique for simultaneous measurements of 16 elements was
also tested in sediments.
PMID- 28495090
TI - Separation of ten phosphorylated mono-and disaccharides using HILIC and ion
pairing interactions.
AB - Phosphorylated carbohydrates are indispensable cogs in several key metabolic
wheels for all forms of life. Here, a straightforward liquid chromatography
method coupled to mass spectrometry detection was developed for phosphorylated
sugars. For separation of the targeted compounds, hydrophilic interaction
chromatography (HILIC) was used with a bridged-ethylene hybrid amide column under
alkaline conditions using triethylamine as a mobile phase modifier.
Methylphosphonic acid was added to the aqueous mobile phase to reduce the tailing
of compounds containing phosphate groups, which are known to interact with
stainless steel components of the separation system. Under alkaline conditions
and addition of methylphosphonic acid, the retention behavior can be attributed
to both conventional HILIC mechanisms as well as ion-pairing interactions in the
mobile phase. This hypothesis is supported by comparing the retention behavior of
phosphorylated sugars and unmodified sugars. The HILIC method resolved eight
biologically important phosphorylated sugars and thereby enables simultaneous
detection and quantification of these compounds: fructose-1,6-bisphosphate,
glucose-1-phosphate, glucose-6-phosphate, lactose-1-phosphate, mannose-6
phosphate, ribose-5-phosphate, sucrose-6-phosphate, and threhalose-6-phosphate.
Fructose-1-phosphate and fructose-6-phosphate were not resolved but
quantification of total fructose-phosphate is possible.
PMID- 28495091
TI - Commentary: Comments regarding Becker et al. (Analytica Chimica Acta, 835, 2014,
1-18).
PMID- 28495092
TI - Response-surface fits and calibration transfer for the correction of the oxygen
effect in the quantification of carbon dioxide via FTIR spectroscopy.
AB - During routine Fourier-Transform Infrared Spectroscopy (FTIR) based
quantification of carbon dioxide in breath, it is necessary to account for a non
linear signal response to the analyte concentration and disturbance factors
arising from the gas background matrix. These factors as well as day-to-day
fluctuation should be corrected via calibration. We present a novel strategy to
combine the information of previous calibrations with a minimal number of actual
calibration measurements to obtain a precise calibration. After decomposition of
the FTIR spectra via principal component analysis (PCA) into scores
(corresponding to intensity) and loadings (corresponding to spectral curves), an
empirical response surface fit equation between scores, analyte concentration and
disturbance factors is established. The fit equation can be characterized via the
coefficients determined by calibration. Out of a pool of coefficients gained from
several calibrations, a multivariate inter-day distribution is generated. By
requiring the coefficient set of the actual calibration to be a sample of the
multivariate inter-day distribution, the number of necessary routine calibration
samples is reduced to two. The corresponding coefficients are determined using
the Lagrange Multipliers approach and the inter-day variability of coefficients
is estimated using Bayesian statistics and Hierarchical models. The best
calibration parameters in terms of calibration equation, wavelength region,
preprocessing options and choice of routine calibration samples were determined;
optimized for minimal number of calibration samples.
PMID- 28495093
TI - Microfabricated disposable nanosensor based on CdSe quantum dot/ionic liquid
mediated hollow fiber-pencil graphite electrode for simultaneous electrochemical
quantification of uric acid and creatinine in human samples.
AB - In this research, a novel sensitive electrochemical nanosensor based on the
cadmium selenide quantum dots (QDs)/ionic liquid mediated hollow fiber-pencil
graphite electrode (HF-PGE) was prepared and applied for simultaneous
determination of uric acid (UA) and creatinine (Crn) in urine and serum samples.
The electrocatalytic oxidation of the analytes was investigated via differential
pulse (DPV) and cyclic voltammetry (CV). The experiments were designed, in two
different steps, according to Taguchi's method; OA9 L9 (33) and OA9 L9 (34)
orthogonal array to optimize experimental runs. The results revealed that the
electrode response was initially influenced by the types of sensor and types of
ionic liquids and their ratios. The amount of QD, buffer pH, equilibration time
and scan rate also influenced electrode response efficiency. According to the
results of Taguchi analysis, the amount of tetra phenyl phosphonium chloride
(TPPC) and QD were the most influencing parameters on the yield response of the
modified electrodes. Linear ranges were obtained between 0.297-2.970 * 103 and
0.442-8.840 * 103 MUM, with the detection limits of 0.083 and 0.229 MUM and
relative standard deviations (RSD) of 2.4% and 1.8%, for UA and Crn,
respectively. Finally, the proposed method was successfully examined for
simultaneous determination of UA and Crn in human urine and serum samples.
PMID- 28495094
TI - Determination of diclofenac using electromembrane extraction coupled with
stripping FFT continuous cyclic voltammetry.
AB - For the first time, on-line and ultra-sensitive determination of trace amount of
diclofenac in whole blood sample was performed by coupling of electromembrane
extraction (EME) and stripping fast Fourier transform continuous cyclic
voltammetry (SFFTCCV). In SFFTCCV, the potential waveform was continuously
applied on a carbon paste electrode and the electrode response was obtained by
subtracting the background current and integrating the current in potential range
of the analyte oxidation. A central composite design was used for the
optimization of the parameters influencing the extraction efficiency. By applying
a DC potential of 20 V during 28 min of extraction, diclofenac was migrated from
the sample solution (pH 5), into a thin layer of 1-octanol immobilized in the
pores of a porous flat sheet membrane and then into the acceptor solution (pH 7).
The method presented a good linearity within the range of 5-1000 ng mL-1 with a
determination coefficient of 0.993 in whole blood samples. Limits of detection
(LOD) and quantification (LOQ) were found to be 1.0 ng mL-1 and 5.0 ng mL-1
respectively.
PMID- 28495095
TI - On-cartridge derivatisation using matrix solid phase dispersion for the
determination of cyclamate in foods.
AB - A novel method for determination of sodium cyclamate in foods was developed. In
this method, a syringe was loaded with the homogeneous mixture of the sample,
KMnO4 powder and silica dispersant and used as a matrix solid phase dispersion
(MSPD) reactor. As the reactor was infiltrated with small amounts of concentrated
HCl, cyclamate was converted to 2-chlorocyclohexanone quickly and effectively
within 5 min and determined by HPLC on a reversed-phase column using UV detection
at a wavelength of 310 nm. Comparing with the traditional derivatisation in
solution, the better clean-up was provided using on-cartridge derivatisation of
MSPD, and much time, labor, and expense were saved. The results showed good
linearity (r2 = 0.9998) over the concentration range of 1-500 mg/L. The limit of
detection (LOD) and limits of quantification (LOQ) of the cyclamate were 0.3 mg/L
and 1 mg/L respectively. The recoveries ranged from 91.6% to 101.3% with the
relative standard deviations (RSDs) in the range of 2.5%-4.3%.
PMID- 28495096
TI - Sequential extraction protocol for organic matter from soils and sediments using
high resolution mass spectrometry.
AB - A vast number of organic compounds are present in soil organic matter (SOM) and
play an important role in the terrestrial carbon cycle, facilitate interactions
between organisms, and represent a sink for atmospheric CO2. The diversity of
different SOM compounds and their molecular characteristics is a function of the
organic source material and biogeochemical history. By understanding how SOM
composition changes with sources and the processes by which it is
biogeochemically altered in different terrestrial ecosystems, it may be possible
to predict nutrient and carbon cycling, response to system perturbations, and
impact of climate change will have on SOM composition. In this study, a
sequential chemical extraction procedure was developed to reveal the diversity of
organic matter (OM) in different ecosystems and was compared to the previously
published protocol using parallel solvent extraction (PSE). We compared six
extraction methods using three sample types, peat soil, spruce forest soil and
river sediment, so as to select the best method for extracting a representative
fraction of organic matter from soils and sediments from a wide range of
ecosystems. We estimated the extraction yield of dissolved organic carbon (DOC)
by total organic carbon analysis, and measured the composition of extracted OM
using high resolution mass spectrometry. This study showed that OM composition
depends primarily on soil and sediment characteristics. Two sequential extraction
protocols, progressing from polar to non-polar solvents, were found to provide
the highest number and diversity of organic compounds extracted from the soil and
sediments. Water (H2O) is the first solvent used for both protocols followed by
either co-extraction with methanol-chloroform (MeOH-CHCl3) mixture, or
acetonitrile (ACN) and CHCl3 sequentially. The sequential extraction protocol
developed in this study offers improved sensitivity, and requires less sample
compared to the PSE workflow where a new sample is used for each solvent type.
Furthermore, a comparison of SOM composition from the different sample types
revealed that our sequential protocol allows for ecosystem comparisons based on
the diversity of compounds present, which in turn could provide new insights
about source and processing of organic compounds in different soil and sediment
types.
PMID- 28495097
TI - Workflow development for targeted lipidomic quantification using parallel
reaction monitoring on a quadrupole-time of flight mass spectrometry.
AB - Advances in high-resolution mass spectrometers with faster scanning capabilities
and higher sensitivities have expanded these instruments' functionality beyond
traditional data-dependent acquisition in targeted metabolomics. Apart from the
traditional multiple reaction monitoring strategy, the parallel reaction
monitoring (PRM) strategy is also used for targeted metabolomics quantification.
The high resolution and mass accuracy of full-scan (MS1) and tandem mass
spectrometry (MS/MS) scan result in sufficient selectivity by monitoring all
MS/MS fragment ions for each target precursor and simultaneously providing
flexibility in assay method construction and post-acquisition data analysis. In
this study, using an orthogonal quadrupole-time of flight liquid chromatography
mass spectrometry system (QTOF LC-MS), we investigated the applicability of a
large-scale targeted lipidomic assay using scheduled PRM. This method monitored
222 lipids belonging to 15 lipid species in serum. Robustness, reproducibility,
and quantitative performance were assessed using chemical standards and serum
samples. Finally, we demonstrated the application of this PRM-based targeted
metabolomic workflow to systemic lupus erythematosus, a severe autoimmunological
disease. Results showed that 63 lipids belonging to 11 lipid species were
significantly changed. In summary, at the first time, a robust targeted lipidomic
workflow was established using PRM acquisition strategy on a Q-TOF platform,
providing another powerful tool for targeted metabolomic analysis.
PMID- 28495098
TI - Polarization-dependent surface-enhanced Raman scattering (SERS) from microarrays.
AB - The convergence between nanometric sensing (e.g. surface-enhanced Raman
scattering - SERS) and lab-on-chip technologies has emerged as a potential
revolutionary approach for a variety of "real-world" applications. Surface
plasmons (SPs) can be excited on metal interfaces through light coupling to
metallic surface gratings. The generation of SPs is a fundamental requirement for
SERS. The work reported in this paper demonstrates a versatile procedure to
prepare both large area (i.e. one inch2) and microarrays (MUarrays) metallic
gratings structures capable of supporting SP excitation (and SERS). Laser
interference lithography (LIL), either alone or combined with traditional laser
photolithography (LPL), was used to generate the periodic patterns. The
fabrication procedure was simple, high-throughput, and reproducible, with array
to-array variations in geometrical parameters of less than 5%. Since the basic
pattern of the nanostructures was a one-dimensional grating, the polarization
anisotropy nature of the substrates was also explored. The use of these
polarization-dependent properties to eliminate non-polarization sensitive
interferences (e.g. spurious spectral background) was demonstrated. Lastly, the
nanostructured gold MUarrays were integrated on a chip for SERS detection of ppm
levels of 8-quinolinol, an emerging pharmaceutical contaminant in aquatic
systems. A low-cost structure for fluid handling was realized by simply using
perforated epoxy membranes. The results demonstrated that the procedure described
here is suitable for the generation of simple integrated MUarrays for SERS
applications in environmental analysis.
PMID- 28495099
TI - A new colorimetric chemosensors for Cu2+ and Cd2+ ions detection: Application in
environmental water samples and analytical method validation.
AB - A new heterocyclic thiophene-2-caboxylic acid hydrazide based chemosensor R1 to
R4 were designed, synthesized and characterized by various spectroscopic
techniques like FT-IR, UV-Vis, 1H NMR, 13C NMR, Mass and SC-XRD. The chemosensor
R3 showed a significant color change from colorless to yellow in the presence of
Cu2+ ions and chemosensor R4 showed a significant color change from colorless to
yellow in the presence of Cd2+ ions over the other tested cations such as Cr3+,
Mn2+, Fe2+, Fe3+, Co2+, Ni2+, Zn2+, Ag2+, Al3+, Pb2+, Hg2+, K+, Ca2+ and Mg2+.
The high selective and sensitivity of R3 towards Cu2+ and R4 towards Cd2+ ions
was confirmed by UV-Vis spectroscopic study. The R3 showed a red shift in the
presence of Cu2+ ions by Deltalambdamax 67 nm and R4 showed a red shift in the
presence of Cd2+ ions by Deltalambdamax 105 nm in the absorption spectrum. The
binding stoichiometric ratio of the complex between R3 - Cu2+ and R4 - Cd2+ ions
have been found to be 1:1 using the B-H plot. Under optimized experimental
conditions, the R3 and R4 exhibits a dynamic linear absorption response range,
from 0 to 50 MUM for Cu2+ ions and 0 to 30 MUM for Cd2+ ions, with the detection
limit of 2.8 * 10-6 M for Cu2+ and 2.0 * 10-7 M for Cd2+ ions. The proposed
analytical method for the quantitative determination of Cu2+ and Cd2+ ions was
validated and successfully applied for the environmental samples with good
precision and accuracy.
PMID- 28495100
TI - Ultrasensitive direct competitive FLISA using highly luminescent quantum dot
beads for tuning affinity of competing antigens to antibodies.
AB - Herein, for the first time we report a novel direct competitive fluorescence
linked immunosorbent assay (dcFLISA) for the ultrasensitive detection of
ochratoxin A (OTA) by introducing a large size polymer beads loaded with quantum
dots (QBs) as carrier of competing antigen for decreasing binding affinity to
antibody and enhancing the fluorescent signal intensity. When using 255 nm QBs as
carrier of competing antigen, the equilibrium dissociation constant of QB based
competing antigen to antibodies can be tuned to 100 times higher than that of the
horseradish peroxidase (HRP) based competing antigen by controlling labeled
amounts of antigen on the surface of QBs. Various parameters that influenced the
sensitivity of dcFLISA were investigated and optimized. Under optimum detection
parameters, the dynamic linear range of developed dcFLISA for detecting OTA was
established at 0.05 pg/mL to 1.56 pg/mL with a half maximal inhibitory
concentration at 0.14 +/- 0.04 pg/mL (n = 5), which is three orders of magnitude
lower than that of conventional HRP-based dcELISA (0.24 ng/mL). The developed
FLISA is also highly accurate, reliable, and shows no cross reaction to other
mycotoxins. In summary, the proposed method offers a straightforward approach to
improve the sensitivity of direct competitive immunoassay for trace small
chemical molecule detection in food quality control, environmental monitoring,
and clinical diagnosis.
PMID- 28495101
TI - Maternal and child health in Israel: building lives.
AB - Israel is home to a child-oriented society that values strong family ties,
universal child benefits, and free education for all children from 3 years of age
to school grade 12. Alongside the universal health-care services that are
guaranteed by the National Health Insurance Law and strong, community-based
primary and preventive care services, these values have resulted in good maternal
and child health. In 2015, infant and maternal mortality (3.1 deaths per 1000
livebirths and 2.0 deaths per 100 000 livebirths, respectively) were lower than
the mean infant and maternal mortality of countries within the Organisation for
Economic Co-operation and Development. Israel has already exceeded the developed
regions' Sustainable Development Goal 2030 targets for maternal mortality,
neonatal mortality, and mortality in children younger than 5 years in all
population groups. Yet these accomplishments are marred by Israel's high
prevalence of child poverty (more than 30%), particularly among Arabs (63%) and
ultra-Orthodox Jews (67%). Although infant mortality has improved in all
subpopulations since Israel was founded in 1948, infant mortality among Arabs is
still more than twice as high as among Jews. To address these disparities in
health, the Israeli Ministry of Health has created a special division and has
funded an intervention programme to reduce the infant mortality among Bedouin
Arabs. Other interventions include targeted and culturally appropriate health
care programmes and services for communities with a high number of at-risk
children and young adults, dental health service for all children up to 15 years,
and improved collaboration between health, education, and welfare services. The
challenges faced by the Israeli health-care system include a growing trend
towards medicalisation of prenatal care, ensuring staff are trained to treat
developmental, behavioural, and psychosocial issues in children and their
families, securing sustainable funding for health promotion and injury prevention
programmes, expanding and improving the coordination of services for children
with special needs or who are at risk, and programme assessment. Ensuring
adequate funding for dedicated, preventive paediatric care and taking action on a
nationwide scale to reduce child poverty are essential for maintaining health
gains in children. In this Series paper, we describe the health indices,
highlight disparities, and discuss the challenges in delivering and maintaining
maternal and child health care in Israel.
PMID- 28495102
TI - Dr David Nabarro is the best candidate for WHO Director-General.
PMID- 28495103
TI - Orly Manor: public health leader in Israel's health system.
PMID- 28495104
TI - Rafael Beyar: a meeting of medicine, science, and technology.
PMID- 28495105
TI - Digital health nation: Israel's global big data innovation hub.
PMID- 28495106
TI - Israel: health and beyond.
AB - The principle that global human identity and dignity supersede other values is a
broadly accepted conviction that guides practice and policies in the realm of
human health in most of the world. An assessment of the level of success that
Israel has achieved in health, in the face of formidable challenges, including
rapid population growth, diverse and often divided ethnic affiliations, and
existential security threats, leads us to propose that extension of this
principle of global human identity and dignity, together with the objective of a
decent society, as overriding values beyond health to other domains of human
endeavour within Israel and in its relations with neighbouring peoples,
represents an entirely achievable imperative. The result will be to further
advance Israel's aspiration to serve as a model for societal decency with wide
international acceptance and engagement. We have identified several determinants
of Israel's advancement in health, including: articulation of a clear vision,
national purpose, and long-term commitment that seeks to take the health of its
citizens seriously; a multi-ethnic population that brings diversity and energy to
national progress; a political democracy, which is characterised by robust debate
and discussion about the nation's future; national legislation governing cardinal
health-care processes; cultural and religious histories that respect and revere
scholarship, learning, research, and charitable donation; an expanding economy,
with recent but increasing appreciation of the economic, social, and political
underpinnings of health and health inequalities; a strong base of international
support from the Diaspora Jewish community; and a strong desire for acceptance by
the international community in key arenas, especially science and health. As a
result, despite the fewer than seven decades since its establishment, Israel has
achieved important milestones in health. Nevertheless, this trajectory of
achievement is threatened by several serious challenges, including the capacity
to sustain high-quality universal health coverage, especially for an ageing
population living with multiple comorbidities in the face of a stagnant level of
the percentage of treasury funding to health care at a level that is well below
the average of the Organisation for Economic Co-operation and Development; ever
increasing transfer of services and care covered by the mandatory public health
services basket to private programmes; insufficient progress in resolving health
disparities among and between communities, populations, and regions of the
country congruent with disparities in income and employment; gender inequities; a
looming increase in the already alarming shortfall in health-care professionals;
and failure to match inpatient and acute care facilities to manage growing needs.
These challenges within Israel are magnified in the context of health disparities
with the neighbouring Palestinian population, a situation in which ongoing-but
fragile and limited-health cooperation and training arrangements cannot stand in
for a solution that will address Palestinian national aspirations. We come away
from this Series with a great sense of optimism, but with specific
recommendations that are based on the foregoing challenges. We believe that by
increasing the investment in the health sector, which includes investing in the
societal, political, educational, and environmental underpinnings of health, far
more can be achieved to move Israel to a model international leadership position
in health care, education, and research, and turn health into an engine for
economic wellbeing and development. Religious leadership in Israel, with its
formidable political influence, can be harnessed to promote health initiatives in
areas ranging from smoking cessation and healthy diet to organ transplantation,
and most of all condemnation of hostility and its replacement by peaceful
resolution of even the deepest conflicts. Most of all, this Series showed that
there is an enormous opportunity, which Israel can lead, to leverage the
universally accepted principles of health as a sanctuary against conflict and
inequity, to achieve a brighter future for a deeply troubled region of the world.
PMID- 28495107
TI - Helping hands across a war-torn border: the Israeli medical effort treating
casualties of the Syrian Civil War.
PMID- 28495108
TI - Medical genetics in Israel's diverse population.
PMID- 28495109
TI - Health and health care in Israel: an introduction.
AB - Starting well before Independence in 1948, and over the ensuing six decades,
Israel has built a robust, relatively efficient public system of health care,
resulting in good health statistics throughout the life course. Because of the
initiative of people living under the British Mandate for Palestine (1922-48),
the development of many of today's health services predated the state's
establishment by several decades. An extensive array of high-quality services and
technologies is available to all residents, largely free at point of service, via
the promulgation of the 1994 National Health Insurance Law. In addition to a
strong medical academic culture, well equipped (albeit crowded) hospitals, and a
robust primary-care infrastructure, the country has also developed some model
national projects such as a programme for community quality indicators, an annual
update of the national basket of services, and a strong system of research and
education. Challenges include increasing privatisation of what was once largely a
public system, and the underfunding in various sectors resulting in, among other
challenges, relatively few acute hospital beds. Despite substantial
organisational and financial investment, disparities persist based on ethnic
origin or religion, other socioeconomic factors, and, regardless of the country's
small size, a geographic maldistribution of resources. The Ministry of Health
continues to be involved in the ownership and administration of many general
hospitals and the direct payment for some health services (eg, geriatric
institutional care), activities that distract it from its main task of planning
for and supervising the whole health structure. Although the health-care system
itself is very well integrated in relation to the country's two main ethnic
groups (Israeli Arabs and Israeli Jews), we think that health in its widest sense
might help provide a bridge to peace and reconciliation between the country and
its neighbours.
PMID- 28495110
TI - Women and health in Israel.
PMID- 28495111
TI - Medical ethics in Israel-bridging religious and secular values.
PMID- 28495112
TI - Inequalities in non-communicable diseases between the major population groups in
Israel: achievements and challenges.
AB - Israel is a high-income country with an advanced health system and universal
health-care insurance. Overall, the health status has improved steadily over
recent decades. We examined differences in morbidity, mortality, and risk factors
for selected non-communicable diseases (NCDs) between subpopulation groups.
Between 1975 and 2014, life expectancy in Israel steadily increased and is
currently above the average life expectancy for the Organisation for Economic Co
operation and Development countries. Nevertheless, life expectancy has remained
lower among Israeli Arabs than Israeli Jews, and this gap has recently widened.
Age-adjusted mortality as a result of heart disease, stroke, or diabetes remains
higher in Arabs, whereas age-adjusted incidence and mortality of cancer were
higher among Jews. The prevalence of obesity and low physical activity in Israel
is considerably higher among Arabs than Jews. Smoking prevalence is highest for
Arab men and lowest for Arab women. Health inequalities are also evident by the
indicators of socioeconomic position and in subpopulations, such as immigrants
from the former Soviet Union, ultra-Orthodox Jews, and Bedouin Arabs. Despite
universal health coverage and substantial improvements in the overall health of
the Israeli population, substantial inequalities in NCDs persist. These
differences might be explained, at least in part, by gaps in social determinants
of health. The Ministry of Health has developed comprehensive programmes to
reduce these inequalities between the major population groups. Sustained
coordinated multisectoral efforts are needed to achieve a greater impact and to
address other social inequalities.
PMID- 28495113
TI - The medical education system in Israel.
PMID- 28495115
TI - A personal perspective on health in Israel.
PMID- 28495114
TI - Coming of age: health-care challenges of an ageing population in Israel.
AB - Although Israel is still young in years, with relatively high birth rates and
older people (individuals aged 65 years or older) constituting only about 11% of
its population, the absolute number of older people is growing rapidly. Life
expectancy is high, and increasing numbers of people are living to advanced old
age (older than 85 years). A wide spectrum of geriatric care is provided within a
universal system providing health services to all citizens. Community and
institutional care is available, and many innovative programmes are being
developed. The unique demographic characteristics of the ageing society in Israel
reflect cultural and multiethnic diversity, in addition to a high rate of
immigration of older people. To meet the growing challenges, address disparities,
and search for innovation will require planning and development of adequate
services at the highest level.
PMID- 28495116
TI - Israel: a start-up life science nation.
PMID- 28495117
TI - First experience with the Watchman FLX occluder for percutaneous left atrial
appendage closure.
AB - BACKGROUND: We aimed to evaluate efficacy and safety of left atrial appendage
(LAA) closure with the new Watchman FLX and analyze procedural features in a
consecutive series of high risk non-valvular atrial fibrillation patients.
METHODS AND RESULTS: Twelve consecutive non-valvular atrial fibrillation patients
(age 76.6+/-7.8years) at high risk for stroke (CHA2DS2-VASc-Score 5.5+/-0.9) and
bleeding (HAS-BLED-Score 3.8+/-0.9), received LAA closure with the Watchman FLX.
Bench testing demonstrated easy repositioning as well as optimized sealing and
anchoring. Follow-up was done at 30days, and at 3 and 6months including
transesophageal echocardiography after 3months. Compression was calculated as
occluder size to diameter at shoulder in final position. The device was
successfully implanted in all patients. Partial recapture was necessary in 6
(50%) of cases, and full recapture in one (8.3%). There were no procedure-related
complications. In 83.3% of cases (N=10/12) compression was between 10 and 27%,
and mean compression was 24.0+/-11.1%. Mean implantation depth was 4.0+/-4.4mm
distal of LAA ostium. There was no residual flow. Proximal shift in device
position was noticed in 2 patients. One device was embolized at 30day follow-up,
and another device showed thrombus formation. There was no disabling or non
disabling stroke through 6months of follow-up with dual antiplatelet therapy for
3months. CONCLUSION: LAA closure with the new Watchman FLX is associated with a
good periprocedural safety, complete sealing of the LAA and simple repositioning.
SUMMARY: We evaluated the efficacy and safety of left atrial appendage (LAA)
closure with the new Watchman FLX and analyzed procedural features in a
consecutive series of high risk non-valvular atrial fibrillation patients. This
is a first observational study demonstrating procedural safety, complete sealing
of the LAA and simple technique for repositioning. There was no stroke within a
6month follow-up.
PMID- 28495118
TI - Complication of descompressive craniectomy: An early "syndrome of the trephined".
PMID- 28495119
TI - Toll-like receptor 3 mediates UVB-induced MMP-13 and MMP-3 expressions in mice.
PMID- 28495120
TI - Combined treatment with H1 and H4 receptor antagonists reduces inflammation in a
mouse model of atopic dermatitis.
AB - BACKGROUND: Histamine 4 receptor (H4R) antagonists are considered as new
therapeutics for the treatment of atopic dermatitis (AD) and first clinical
trials have already shown promising results. Histamine 1 receptor (H1R)
antagonists are traditionally used to treat AD although the evidence for the
efficacy is weak. The combined blockade of both, H1R and H4R, might provide
synergistic anti-inflammatory. OBJECTIVE: The study was performed to test the
anti-inflammatory potential of a combined treatment with an H1R and an H4R
antagonist in a mouse AD model. METHODS: The development of ovalbumin-induced AD
like skin lesions was analysed mice treated with the H1R inverse agonist
mepyramine, the H4R antagonist JNJ-39758979 or a combination of both. RESULTS:
Mice treated with mepyramine plus JNJ-39758979 showed less severe skin lesions,
with a diminished influx of inflammatory cells, a reduced epidermal thickening
and a lower level of IL-33 in lesional skin. Scratching behaviour was ameliorated
in mice treated with the combination. Moreover, total numbers of skin-draining
lymph node cells and splenocytes were significantly reduced. Both substances
given alone did not elicit this strong anti-inflammatory effect. CONCLUSION: H1R
and H4R antagonists provide synergistic anti-inflammatory effects in a mouse
model of AD. The combined therapy with H1R and H4R antagonists might represent a
new strategy for the treatment of AD.
PMID- 28495121
TI - Approaches to appropriate care delivery from a policy perspective: A case study
of Australia, England and Switzerland.
AB - BACKGROUND: Appropriateness is a conceptual way for health systems to balance
Triple Aim priorities for improving population health, containing per capita
cost, and improving the patient experience of care. Comparing system approaches
to appropriate care delivery can help health systems establish priorities and
facilitate appropriate care practices. METHODS: We conceptualized system
appropriateness by identifying policies that aim to achieve the Triple Aim and
their consequent trade-offs for financing, clinical practice, and the individual
patient. We used secondary data sources to compare the appropriate care
approaches of Australia, England, and Switzerland according to financial,
clinical, and individual appropriateness policies. FINDINGS: Health system
approaches to appropriate care delivery varied. England prioritizes public
health, equity and efficiency at the expense of individual choice, while
Switzerland focuses on individual patient preferences, but has higher per capita
and out of pocket costs. Australia provides equity in public care access and
private health care options that allows for more patient choice, with health care
costs falling between the two. CONCLUSIONS: Integrating the Triple Aim into
health system design and policy can facilitate appropriate care delivery at the
system, clinical, and individual levels. Approaches will vary and require
countries to negotiate and justify priorities and trade-offs within the context
of thehealth system.
PMID- 28495123
TI - In Response to "Hypothermia for Neuroprotection in Convulsive Status
Epilepticus".
PMID- 28495122
TI - Next Generation Sequencing uncovers within-host differences in the genetic
diversity of Cryptosporidium gp60 subtypes.
AB - The extent of within-host genetic diversity of parasites has implications for our
understanding of the epidemiology, disease severity and evolution of parasite
virulence. As with many other species, our understanding of the within-host
diversity of the enteric parasite Cryptosporidium is changing. The present study
compared Sanger and Next Generation Sequencing of glycoprotein 60 (gp60)
amplicons from Cryptosporidium hominis (n=11), Cryptosporidium parvum (n=22) and
Cryptosporidium cuniculus (n=8) DNA samples from Australia and China. Sanger
sequencing identified only one gp60 subtype in each DNA sample: one C. hominis
subtype (IbA10G2) (n=11), four C. parvum subtypes belonging to IIa (n=3) and IId
(n=19) and one C. cuniculus subtype (VbA23) (n=8). Next Generation Sequencing
identified the same subtypes initially identified by Sanger sequencing, but also
identified additional gp60 subtypes in C. parvum and C. cuniculus but not in C.
hominis, DNA samples. The number of C. parvum and C. cuniculus subtypes
identified by Next Generation Sequencing within individual DNA samples ranged
from two to four, and both C. parvum IIa and IId subtype families were identified
within the one host in two samples. The finding of the present study has
important implications for Cryptosporidium transmission tracking as well as
vaccine and drug studies.
PMID- 28495124
TI - Using visual demonstrations in young adults to promote smoking cessation:
Preliminary findings from a French pilot study.
AB - BACKGROUND: A personalised, smoking cessation message was successfully delivered
in Australian community pharmacies to motivate behavioural change in young
smoking adults. OBJECTIVE: The purpose of this pilot study was to test the
acceptability and effectiveness of the innovative, proven smoking cessation
intervention to another population of young adults with a higher prevalence of
smoking and associated morbidities. METHODS: Ninety eight university students in
Paris, France were recruited to a pilot study (50 intervention: 48 control). All
students received smoking cessation counselling sessions and half also received a
visual demonstration of themselves, both as a lifelong smoker and non-smoker.
RESULTS: There was no statistical significant difference between the groups in
smoking dependence at recruitment. At the three month follow-up, the proportion
who had attempted to quit smoking were 37% (control) vs 46% (intervention). These
percentages suggested a positive result for the intervention, although the
difference was not statistically significant (p = 0.39). CONCLUSION: This is one
of the first studies conducted in France using visual demonstrations combined
with healthcare counselling to promote smoking cessation amongst young adult
smokers. Further research, recruiting from the general French public, is needed
to better understand if the innovative personalised health message can motivate
young French adult smokers to quit.
PMID- 28495125
TI - Comparative study of presurgical hand hygiene with hydroalcoholic solution versus
traditional presurgical hand hygiene.
AB - OBJECTIVE: To compare presurgical hand hygiene with hydroalcoholic solution
following the WHO protocol with traditional presurgical hand hygiene. METHODS:
Cultures of the hands of surgeons and surgical nurses were performed before and
after presurgical hand hygiene and after removing gloves at the end of surgery.
Cultures were done in 2different days: the first day after traditional
presurgical hand hygiene, and the second day after presurgical hand hygiene with
hydroalcoholic solution following the WHO protocol. The duration of the
traditional hand hygiene was measured and compared with the duration (3min) of
the WHO protocol. The cost of the products used in the traditional technique was
compared with the cost of the hydroalcoholic solution used. The variability of
the traditional technique was determined by observation. RESULTS: Following
presurgical hand hygiene with hydroalcoholic solution, colony-forming units (CFU)
were detected in 5 (7.3%) subjects, whereas after traditional presurgical hand
hygiene CFU were detected in 14 subjects (20.5%) (p < 0.05). After glove removal,
the numbers of CFU were similar. The time employed in hand hygiene with
hydroalcoholic solution (3min) was inferior to the time employed in the
traditional technique (p < 0.05), its cost was less than half, and there was no
variability. CONCLUSIONS: Compared with other techniques, presurgical hand
hygiene with hydroalcoholic solution significantly decreases CFU, has similar
latency time, a lower cost, and saves time.
PMID- 28495126
TI - Recanalisation of Bronchial Venous Plexuses in Superior Venous Cava Occlusion.
PMID- 28495127
TI - Spontaneous Regression of a Gigantic Cardiac Rhabdomyoma.
PMID- 28495128
TI - Ulcerative nodules on the perineum.
PMID- 28495129
TI - [Generic drugs controversy in oncology].
PMID- 28495130
TI - Prognostic value of oligoclonal IgG bands in Japanese clinically isolated
syndrome converting to clinically definite multiple sclerosis.
AB - We evaluated the impact of brain MRI findings and oligoclonal IgG bands (OCBs) on
conversion to clinically definite multiple sclerosis (CDMS) in 26 Japanese
patients with clinically isolated syndrome (CIS). 19.2% had OCBs positivity and
3.8% had fulfillment of Barkhof criteria at baseline. 60.0% of CIS patients with
positive OCBs and 9.5% of those with negative OCBs developed CDMS during
60.6months. Japanese CIS patients with positive OCBs have an equivalent risk of
developing CDMS. A hypothesis that Japanese CIS patients may have substantially
less OCBs positivity, MRI lesions, and conversion ratio than Caucasians, should
be further tested.
PMID- 28495131
TI - Massive intracerebral Epstein-Barr virus reactivation in lethal multiple
sclerosis relapse after natalizumab withdrawal.
AB - Rebound of disease activity in multiple sclerosis patients after natalizumab
withdrawal is a potentially life-threatening event. To verify whether highly
destructive inflammation after natalizumab withdrawal is associated with Epstein
Barr virus (EBV) reactivation in central nervous system infiltrating B-lineage
cells and cytotoxic immunity, we analyzed post-mortem brain tissue from a patient
who died during a fulminating MS relapse following natalizumab withdrawal.
Numerous EBV infected B cells/plasma cells and CD8+ T cells infiltrated all white
matter lesions; the highest frequency of EBV lytically infected cells and
granzyme B+ CD8+ T cells was observed in actively demyelinating lesions. These
results may encourage switching to B-cell depleting therapy after natalizumab
discontinuation.
PMID- 28495132
TI - Predicting the effects of potentially therapeutic modified peptides on polyclonal
T cell populations in a mouse model of multiple sclerosis.
AB - Altered peptide ligands (APLs) have routinely been studied in clonal populations
of Th cells that express a single T cell receptor (TCR), but results generated in
this manner poorly predict the effects of APLs on polyclonal Th cells in vivo,
contributing to the failure of phase II clinical trials of APLs in autoimmune
diseases such as multiple sclerosis (MS). We have used a panel of APLs derived
from an encephalitogenic epitope of myelin proteolipid protein to investigate the
relationship between antigen cross-reactivity in a polyclonal environment,
encephalitogenicity, and the capacity of an APL to provide protection against
experimental autoimmune encephalomyelitis (EAE) in SJL mice. In general,
polyclonal Th cell lines specific for encephalitogenic APLs cross-reacted with
other encephalitogenic APLs, but not with non-encephalitogenic APLs, and vice
versa. This, alongside analysis of TCR Vbeta usage, suggested that
encephalitogenic and non-encephalitogenic subgroups of APLs expand largely non
cross-reactive Th cell populations. As an exception to the rule, one non
encephalitogenic APL, L188, induced proliferation in polyclonal CD4+ T cells
specific for the native encephalitogen, with minimal induction of cytokine
production. Co-immunization of L188 alongside the native encephalitogen slightly
enhanced disease development. In contrast, another APL, A188, which induced IL-10
production without proliferation in CD4+ T cells specific for the native
encephalitogen, was able to protect against development of EAE in a dose
dependent fashion when co-immunized alongside the native encephalitogen. These
results suggest that testing against polyclonal Th cell lines in vitro may be an
effective strategy for distinguishing between potentially therapeutic and non
therapeutic APLs.
PMID- 28495134
TI - Reevaluating the role of IDO1: Examining NAD+ metabolism in inflammation.
PMID- 28495133
TI - Multiple sclerosis in India: Iceberg or volcano.
AB - Multiple sclerosis (MS)1 is a chronic neurodegenerative disease involving
destruction of the myelin sheath around axons of the brain, spinal cord and optic
nerve. There has been a tremendous transformation in its perspective across
globe. In recent years, its prevalence has changed dramatically worldwide and
India is no exception. Initially, MS was believed to be more common in the
Caucasians of Northern Europe and United States; however, it has been found to be
present in Indian subcontinent as well. There has been a considerable shift in MS
prevalence in India and this has really changed the notion of considering India
as a low risk zone for MS. In this review, a concise overview and latest update
on changing scenario of MS in India is presented along with some major challenges
regarding it persisting across globe even today. In India, remarkable upsurge is
needed in carrying out large scale population-based epidemiological studies to
get an idea about the true incidence and prevalence rates of MS viz a viz disease
burden. Through this review, we have probably tried to identify the actual
picture of MS prevalence in India and this could serve as harbinger for upcoming
research and at the same time it would definitely aid in working out future
strategies for MS management in the country.
PMID- 28495135
TI - Inflammatory cytokines and functional impairment in drug-free subjects with mood
disorder.
AB - OBJECTIVE: To assess the association between peripheral levels of inflammatory
cytokines and functional impairment in subjects with Bipolar Disorder (BD), Major
Depressive Disorder (MDD) and population controls. METHODS: This was a cross
sectional study with a matched sample of drug-free young adults with BD (n=48),
MDD (n=48) and population controls (n=48). Mood disorder was confirmed by a
certified psychologist using the Structured Clinical Interview for DSM-IV (SCID
I). Functional impairment was assessed using the Functional Assessment Short Test
(FAST). Serum levels of IL-6 and IL-10 were measured by ELISA. RESULTS:
Peripheral levels of IL-6 and IL-10 were not significantly different between
subjects with BD, MDD compared to controls. Higher levels of functional
impairment were verified in subjects with BD and MDD compared to population
controls (p<=0.001). In addition, IL-6 and IL-10 levels were positively
correlated with functional impairment in subjects with BD (IL-6: r=0.349,
p=0.016; and IL-10: r=0.351, p=0.016). CONCLUSION: Inflammatory dysregulation was
associated with functional impairment among drug-free subjects with BD. This
finding suggests that inflammatory dysregulation may be involved in the
neuroprogression of BD.
PMID- 28495137
TI - Early predictors of rapidly evolving multiple sclerosis: A case report.
AB - : Objective The aim of this case report is to highlight some important features
of rapidly evolving Multiple Sclerosis. BACKGROUND: In a small proportion of
patients, Multiple Sclerosis (MS) can present as a fulminant disease
characterised by severe and frequent relapses. This form of rapidly evolving MS
is associated with significant morbidity and mortality. It is therefore important
to identify these patients as early as possible, so that they can be managed
effectively. However, due to the rarity of fulminant forms of MS, there is
limited data on the natural history and management of this condition. CASE
REPORT: We present a young man with rapidly evolving Multiple Sclerosis (MS) who
had 2 disabling relapses within 14weeks. He had an unusually high CSF white cell
count at presentation (86per mm3; 100% lymphocytes, 97% T cells, 3% B cells),
with positive oligoclonal bands. Brain MRI showed large, cavitating lesions, with
no enhancement. He required a prolonged course of intravenous methyl-prednisolone
and plasma exchange. CONCLUSIONS: This case suggests that male gender, young age
at onset, time to second relapse, relapse severity, high CSF white cell count at
presentation, large and cavitating lesions on MRI may be early predictors of
rapidly evolving MS. It also highlights the therapeutic value of plasma exchange
and longer courses of intravenous methylprednisolone in managing severe MS
relapses. Enhancement may not always be a reliable indicator of disease activity,
particularly in clinical settings where single dose gadolinium is used, due to
its low sensitivity in detecting blood brain barrier leakage.
PMID- 28495136
TI - Heritability of plasma neopterin levels in the Old Order Amish.
AB - BACKGROUND: We examined the heritability of neopterin, a biomarker for cell
mediated immunity and oxidative stress, and potentially for psychiatric
disorders, in the Old Order Amish. METHODS: Plasma neopterin levels were
determined in 2015 Old Order Amish adults. Quantitative genetic procedures were
used to estimate heritability of neopterin. RESULTS: Heritability of log
neopterin was estimated at 0.07 after adjusting for age, gender, and household
(p=0.03). The shared household effect was 0.06 (p<0.02). CONCLUSIONS: We found a
low heritability of neopterin and small household effect, suggesting that non
household environmental factors are more important determinants of variance of
neopterin levels in the Amish.
PMID- 28495138
TI - Effect of ethnic origin and gender on the clinical manifestations of myasthenia
gravis among the Jewish population in Israel.
AB - Reports on patients with myasthenia gravis (MG) of different ethnic origins
demonstrated differences in weakness distribution and serological results. We
studied MG characteristics in a cohort of Ashkenazi (ASH) and non-Ashkenazi
(NASH) Jewish origin according to their ethnic origins and gender. The frequency
of age of MG onset was distributed in a bi-modal fashion in the female patients
and increased gradually over time, with a peak around 70years of age in the male
patients. Ocular MG was more frequent in males and ASH patients. Unlike previous
reports, our male patients had a higher proportion of positive serum anti-acetyl
choline receptor (AChR) than female patients, with no ethnic-based differences in
the rates of anti-AChR or anti-muscle specific kinase. Comorbidity with another
autoimmune disease was more frequent among female patients with late-onset MG and
NASH patients (mainly Israel-born). Male MG patients tended to have more
malignant comorbidities than female MG patients. These results demonstrate the
effect of ethnicity on clinical aspects of MG within the Jewish population in
Israel, and reveal novel effects of gender-associated comorbidities in patients
with MG.
PMID- 28495139
TI - High yield primary microglial cultures using granulocyte macrophage-colony
stimulating factor from embryonic murine cerebral cortical tissue.
AB - BACKGROUND: Microglia play vital roles in neurotrophic support and modulating
immune or inflammatory responses to pathogens or damage/stressors during disease.
This study describes the ability to establish large numbers of microglia from
embryonic tissues with the addition of granulocyte-macrophage stimulating factor
(GM-CSF) and characterizes their similarities to adult microglia examined ex vivo
as well as their responses to inflammatory mediators. METHOD: Microglia were
seeded from a primary embryonic mixed cortical suspension with the addition of GM
CSF. Microglial expression of CD45, CD11b, CD11c, MHC class I and II, CD40, CD80,
and CD86 was analyzed by flow cytometry and compared to those isolated using
different culture methods and to the BV-2 cell line. GM-CSF microglia
immunoreactivity and cytokine production was examined in response to
lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). RESULTS: Our results
demonstrate GM-CSF addition during microglial culture yields higher cell numbers
with greater purity than conventionally cultured primary microglia. We found that
the expression of immune markers by GM-CSF microglia more closely resemble adult
microglia than other methods or an immortalized BV-2 cell line. Primary
differences amongst the different groups were reflected in their levels of CD39,
CD86 and MHC class I expression. GM-CSF microglia produce CCL2, tumor necrosis
factor-alpha, IL-6 and IL-10 following exposure to LPS and alter costimulatory
marker expression in response to LPS or IFN-gamma. Notably, GM-CSF microglia were
often more responsive than the commonly used BV-2 cell line which produced
negligible IL-10. CONCLUSION: GM-CSF cultured microglia closely model the
phenotype of adult microglia examined ex vivo. GM-CSF microglia are robust in
their responses to inflammatory stimuli, altering immune markers including Iba-1
and expressing an array of cytokines characteristic of both pro-inflammatory and
reparative processes. Consequently, the addition of GM-CSF for the culturing of
primary microglia serves as a valuable method to increase the potential for
studying microglial function ex vivo.
PMID- 28495140
TI - Multiple sclerosis risk pathways differ in Caucasian and Chinese populations.
AB - Large-scale genome-wide association study (GWAS) datasets provide strong support
for investigations of the mechanisms underlying multiple sclerosis (MS) by using
pathway analysis methods. In our recent study, we conducted a three-stage pathway
analysis of GWAS and expression datasets. After identifying 15 shared MS pathways
in separate MS GWAS datasets, we found that dysregulated MS genes were
significantly enriched in 10 of the 15 MS risk pathways. Evidence showed that 17%
30% of genes are differentially expressed among individual ethnic populations. We
then verified the potential disruption of genes in the 10 MS risk pathways cited
above in Chinese MS patients. Here, we investigated potential up- and down
regulation of 42 MS genes in these 10 MS risk pathways using 132 Chinese MS
patients and 76 healthy control subjects. We then identified 31 differentially
expressed genes in Chinese MS patients compared to healthy control subjects.
Moreover, the expression patterns of 28 of these genes were consistent with those
obtained from Caucasian (European and American) MS patients, although 14 genes
differed from the latter group's. Our results provide clinically useful clues
about the link between these risk genes and MS susceptibility in the Chinese
population.
PMID- 28495141
TI - Association of lower serum Brain-derived neurotrophic factor levels with larger
infarct volumes in acute ischemic stroke.
AB - OBJECTIVE: Brain-derived neurotrophic factor (BDNF) plays a potential role in
stroke recovery, as it promotes plasticity. The aim of this study is to
investigate the association between infarct volume using DWI and BDNF at
admission in patients with acute ischemic stroke (AIS). METHODS: The study
population comprised consecutive patients with an AIS diagnosis who had been
referred to our hospital between January 2015 and June 2016. The severity of
stroke was evaluated by the National Institutes of Health Stroke Scale (NIHSS) at
admission. Infarct volumes indicated by DWI were measured with MIPAV software.
The relationship between median DWI infarct volume and serum BDNF level quartiles
was evaluated using a semiparametric approach with univariate and multivariate
quartile regression analysis. RESULTS: In this study, 270 patients were included
and met the study criteria. The median DWI infarct volumes for the serum BDNF
level quartiles (lowest to highest) were 10.56, 5.13, 3.75 and 2.43ml.
Nonparametric Spearman rank correlation revealed a statistically significant
negative correlation between serum BDNF level and DWI infarct volume (r=-0.363;
P<0.001). The median DWI infarct volume in the lowest BDNF quartile was
significantly larger than those in the upper 3 quartiles (P<0.001). Further,
median adjusted DWI infarct volumes (IQR) for each of the BDNF level quartiles
were 7.77, 4.56, 3.75, and 2.43ml from lowest to highest quartiles. CONCLUSIONS:
Larger stroke infarct volumes using DWI are associated with lower levels of BDNF
at admission. Further investigations are suggested to elucidate the role of BDNF
as part of a potential neuroprotective strategy.
PMID- 28495142
TI - N-methyl-d-aspartate receptor-mediated calcium overload and endoplasmic reticulum
stress are involved in interleukin-1beta-induced neuronal apoptosis in rat
hippocampus.
AB - Increased levels of interleukin (IL)-1beta and its gene expression are implicated
in the etiology of Alzheimer's disease (AD). IL-1beta activates microglia and
stimulates glutamatergic N-methyl-d-aspartate receptor NMDA receptor expression,
thereby disturbing intracellular Ca2+ homeostasis. Ca2+ disequilibrium, in turn,
may trigger endoplasmic reticulum (ER) stress, contributing to overall
excitotoxicity and neuronal death that evoke AD. However, it is unclear whether
IL-1beta-induced neuronal apoptosis is mediated by the glutamatergic system, ER
stress and/or Ca2+ dysfunction. The present study investigated the role of NMDA
receptor (NMDAR) in ER stress and IL-1beta-evoked neuronal death by assessing
NMDAR-induced Ca2+ overload and NMDA-mediated ER stress. Male Long Evans rats
were treated with IL-1beta (with or without NMDAR antagonist MK801) injected
intracerebroventricularly for 8days. Glutamate concentration was measured by
HPLC, and mRNA and protein expression of microglial biomarkers and NMDAR, as well
as markers of Ca2+ overload (caplain2) and ER stress (glucose-regulated protein
78, GRP78, and C/EBP homologous protein-10, CHOP), were assessed by real-time PCR
and western blot. Apoptosis was also evaluated in the hippocampal neurons using
TUNEL. Overall, IL-1beta induced robust neuronal apoptosis, accompanied by
upregulated NMDAR, caplain2, GRP78 and CHOP. MK801 pretreatment significantly
attenuated neuronal apoptosis and NMDA up-regulation, also reducing GRP78 and
CHOP expression. In summary, these results suggest that IL-1beta may disturb
intracellular Ca2+ homeostasis via NMDAR-mediated mechanism, thereby triggering
neuronal apoptosis by enhancing ER stress.
PMID- 28495143
TI - Central and peripheral nervous system immune-mediated demyelinating disease after
allogeneic hematopoietic stem cell transplantation.
AB - OBJECTIVE: We aimed to evaluate clinical and diagnostic features of central and
peripheral immune-mediated demyelinating disease (CPID) in allogeneic
hematopoietic stem cell transplantation (aHSCT) recipients. BACKGROUND: CPID
refers to the late-onset, immune-mediated neurological complications following
aHSCT, when other frequent differential diagnoses have been ruled out, and when
symptoms and signs of systemic GvHD manifestations are absent. METHODS: Case
records at the University of Tuebingen, between 2001 and 2015, were screened to
identify patients with CPID after aHSCT. RESULTS: Seven patients who developed
CPID after aHSCT were identified. The average time interval from aHSCT until
onset of CPID was 2.6 (+/-2.8) years (mean+/-SD). The most prevalent
manifestations of CPID were optic neuritis and/or myelitis and polyneuropathy.
Cerebrospinal fluid analyses involved elevated protein concentration and
lymphocytic pleocytosis, while oligoclonal bands in CSF, but not in serum, were
detected in 28% of cases. Aquaporin-4-antibodies were consistently absent. MRI
studies showed features suggestive of demyelination processes, with cerebral
and/or spinal cord white-matter involvement, and features compatible with
cerebral vasculitis. Corticosteroids, Immunoglobulins, Cyclophosphamide,
Rituximab and Interferon beta-1a showed marginal treatment responses, whereas
plasma exchange resulted in marked clinical improvement in two treated patients.
A chronic disease-course with persisting neurological deficits was prevalent.
CONCLUSIONS: CPID may comprise a rare complication of aHSCT, which manifests as
optic neuritis and/or myelitis and is accompanied by sensorimotor polyneuropathy.
A concomitant systemic manifestation of GvHD is not mandatory for CPID diagnosis.
Usually, CPID exhibits a chronic, persisting disease course. Thus, clinical
awareness is required, as early diagnosis and aggressive treatment may be
prognostically advantageous.
PMID- 28495144
TI - Expansion of IL-6+ Th17-like cells expressing TLRs correlates with microbial
translocation and neurological disabilities in NMOSD patients.
AB - Different microbial antigens, by signaling through toll-like receptors (TLR), may
contribute to Th17-mediated autoimmune diseases, such as neuromyelitis optica
spectrum disorder (NMOSD). The objective of this study was to determine the
proportion of different Th17-like cell subsets that express TLR in NMOSD
patients. For this study, the frequency of different Th17 cell subsets expressing
TLR subsets in healthy individuals (n=20) and NMOSD patients (n=20) was evaluated
by cytometry. The peripheral levels of soluble CD14 (sCD14) and cytokines were
determined by ELISA. Our results demonstrated that the proportion of peripheral
CD4+ T cells expressing TLR2, 4 and 9 was significantly higher in NMOSD samples
than in healthy subjects. In NMOSD, these cells are CD28+PD-1-CD57- and produce
elevated levels of IL-17. Among different TLRs+ Th17-like subsets, the proportion
of those that co-express IL-17 and IL-6 was significantly higher in NMOSD
patients, which was positively correlated with sCD14 levels and EDSS score. By
contrast, the percentage of TLRs+Treg17 cells (IL-10+IL-17+) was negatively
related to sCD14 and the severity of NMOSD. In conclusion, the expansion of
peripheral IL-6-producing TLR+ Th17-like cells in NMOSD patients was associated
with both bacterial translocation and disease severity.
PMID- 28495145
TI - Medication discrepancy rates among Medicaid recipients at hospital discharge.
AB - OBJECTIVES: To compare the rate of discrepancies per patient for medications
changed during hospitalization in patients with and without prescription provider
comments at hospital discharge. Secondary objectives included comparing 35-day
readmission rates, describing the overall medication discrepancy rate stratified
by age group and type of discrepancy, collecting average number of medication
changes, and reporting percentage change in admission medications at discharge.
METHODS: This single-center prospective cohort included NC Medicaid recipients
discharged from East Carolina University Family Medicine service from November 1,
2015, to January 31, 2016. Patients were assigned to a group based on presence or
absence of provider comments on discharge prescriptions. Outpatient pharmacy
claims were compared with the discharge summary to identify medication
discrepancies. Medication discrepancy rates between groups were to be compared by
means of independent-samples t test. Medication discrepancy rates were compared
according to 35-day readmission status, age group, and type of discrepancy by
means of independent-samples t tests and analysis of variance. Descriptive
statistics were used for other secondary outcomes. RESULTS: Of 118 patients
included, only 1 had provider comments. Therefore, a medication discrepancy rate
comparison was not performed. Patients had a mean of 4 medication changes made to
their regimen and 21.3% change in admission medications. Sixty-one percent of
patients had at least 1 medication discrepancy, with an overall rate of 1.19.
Patients readmitted within 35 days had a significantly greater medication
discrepancy rate than those not readmitted (1.63 vs. 1.05, respectively; P =
0.044). Patients 18-49 years of age had the highest discrepancy rate and those
older than 80 years of age the lowest (1.58 and 0.50, respectively). New or
changed discharge medication not filled accounted for 69% of discrepancies.
CONCLUSION: Although medication discrepancies were common, use of provider
comments was rare. Future studies should address more effective ways to
communicate pertinent information to community pharmacists and methods to improve
adherence in obtaining new medications.
PMID- 28495146
TI - Neonatal Vein of Labbe Infarction Size is Associated With Long-Term Language
Outcomes.
AB - BACKGROUND: The vein of Labbe is a superficial cortical vein, which drains the
lateral surface of the temporal lobe. Thrombosis of the vein of Labbe can occur
in the neonatal period. The developmental outcomes of infants who had vein of
Labbe thrombosis are unknown as few studies of outcomes exist. METHODS: We
completed a retrospective review of infants born >=34 weeks of gestation,
diagnosed with vein of Labbe thrombosis, and/or infarction on neuroimaging during
the first 30 days of life. Size of each temporal lobe infarction was estimated
based on the number of temporal lobe segments involved. Primary outcomes were the
presence of major neurodevelopmental impairments in childhood and Bayley scores
at two years. RESULTS: Our cohort of 19 infants had a median gestational age of
38 weeks (interquartile range 36 to 39) and mean birth weight 2892 +/- 920 grams.
The most common presenting symptoms of vein of Labbe thrombosis and infarction of
surrounding tissue were seizures, apnea, lethargy, and either hypertonia or
hypotonia. At the latest clinical follow-up appointment documented in the
electronic medical record (mean 4.4 +/- 3.08 years), 44% had major
neurodevelopmental impairment. Patients with large vein of Labbe infarctions had
significantly worse average Bayley scores than those with small to moderate
lesions, and differences in language composite were statistically significant
(72.7 vs 107.8, P = 0.017). CONCLUSIONS: Neonates with large vein of Labbe
infarctions are more likely to have poor language outcomes. This finding suggests
a need for targeted surveillance to ensure early identification of deficits and
referral for intervention.
PMID- 28495148
TI - Analysis of urinary PSA glycosylation is not indicative of high-risk prostate
cancer.
AB - The levels of core fucosylation and alpha2,3-linked sialic acid in serum Prostate
Specific Antigen (PSA), using the lectins Pholiota squarrosa lectin (PhoSL) and
Sambucus nigra agglutinin (SNA), can discriminate between Benign Prostatic
Hyperplasia (BPH) and indolent prostate cancer (PCa) from aggressive PCa. In the
present work we evaluated whether these glycosylation determinants could also be
altered in urinary PSA obtained after digital rectal examination (DRE) and could
also be useful for diagnosis determinations. For this purpose, alpha2,6-sialic
acid and alpha1,6-fucose levels of urinary PSA from 53 patients, 18 biopsy
negative and 35 PCa patients of different aggressiveness degree, were analyzed by
sandwich ELLA (Enzyme Linked Lectin Assay) using PhoSL and SNA. Changes in the
levels of specific glycosylation determinants, that in serum PSA samples were
indicative of PCa aggressiveness, were not found in PSA from DRE urine samples.
Although urine is a simpler matrix for analyzing PSA glycosylation compared to
serum, an immunopurification step was necessary to specifically detect the
glycans on the PSA molecule. Those specific glycosylation determinants on urinary
PSA were however not useful to improve PCa diagnosis. This could be probably due
to the low proportion of PSA from the tumor in urine samples, which precludes the
identification of aberrantly glycosylated PSA.
PMID- 28495147
TI - Discrepancies between two immunoassays for the determination of MPO and PR3
autoantibodies.
AB - BACKGROUND: Testing for autoantibodies to myeloperoxidase (MPO) and proteinase 3
(PR3) is part of anti-neutrophil cytoplasmic antibodies (ANCA) test that aids the
diagnosis of a number of autoimmune diseases including small-vessel vasculitis.
We characterized the differences between two automated immunoassays at three
facilities for measuring MPO- and PR3-ANCA autoantibodies. METHODS: 117 serum
samples were analyzed for MPO and PR3 autoantibodies. The INOVA QUANTA Lite(r)
IgG assay (INOVA Diagnostics) were performed at two facilities and the Bio
Plex(r) 2200 Vasculitis Panel (Bio-Rad) were performed at a third reference lab.
The results were compared both qualitatively (between INOVA QUANTA Lite(r) and
Bio-Plex(r) methods) and quantitatively (between two sites performing INOVA
QUANTA Lite(r) assays). RESULTS: Comparison of the INOVA QUNATA Lite(r) assays at
two different facilities (n=36) demonstrated high concordance (97.2% for MPO and
94.4% for PR3) and quantitative correlation (R2=0.973 for MPO and R2=0.935 for
PR3). Conversely, INOVA QUNATA Lite(r) and Bio-Plex(r) methods showed poor
concordance at 70.4% for MPO (n=81; 95% CI: 59.7% to 79.2%) and at 76.5% for PR3
(n=81; 95% CI: 66.2% to 84.4%). CONCLUSION: This study demonstrated low
concordance between two methods for MPO-ANCA and PR3-ANCA measurements. Given the
discrepancies, the performance of different autoantibody immunoassay methods
should be taken into consideration when evaluating MPO-ANCA and PR3-ANCA results.
PMID- 28495151
TI - Research integrity-have we made progress?
PMID- 28495149
TI - United States Multicenter Clinical Trial of Corneal Collagen Crosslinking for
Keratoconus Treatment.
AB - PURPOSE: To evaluate the safety and efficacy of corneal collagen crosslinking
(CXL) for the treatment of progressive keratoconus. DESIGN: Prospective,
randomized, multicenter, controlled clinical trial. PARTICIPANTS: Patients with
progressive keratoconus (n = 205). METHODS: The treatment group underwent
standard CXL and the sham control group received riboflavin alone without removal
of the epithelium. MAIN OUTCOME MEASURES: The primary efficacy criterion was the
change over 1 year of topography-derived maximum keratometry value, comparing
treatment with control group. Secondary outcomes evaluated were corrected
distance visual acuity (CDVA), uncorrected distance visual acuity (UDVA),
manifest refraction spherical equivalent, endothelial cell count, and adverse
events. RESULTS: In the CXL treatment group, the maximum keratometry value
decreased by 1.6 diopters (D) from baseline to 1 year, whereas keratoconus
continued to progress in the control group. In the treatment group, the maximum
keratometry value decreased by 2.0 D or more in 28 eyes (31.5%) and increased by
2.0 D or more in 5 eyes (5.6%). The CDVA improved by an average of 5.7 logarithm
of the minimum angle of resolution (logMAR) units. Twenty-three eyes (27.7%)
gained and 5 eyes lost (6.0%) 10 logMAR or more. The UDVA improved 4.4 logMAR.
Corneal haze was the most frequently reported CXL-related adverse finding. There
were no significant changes in endothelial cell count 1 year after treatment.
CONCLUSIONS: Corneal collagen crosslinking was effective in improving the maximum
keratometry value, CDVA, and UCVA in eyes with progressive keratoconus 1 year
after treatment, with an excellent safety profile. Corneal collagen crosslinking
affords the keratoconic patient an important new option to decrease progression
of this ectatic corneal process.
PMID- 28495152
TI - An ounce of prevention.
PMID- 28495150
TI - Personalized Prognosis of Uveal Melanoma Based on Cytogenetic Profile in 1059
Patients over an 8-Year Period: The 2017 Harry S. Gradle Lecture.
AB - PURPOSE: To determine the personalized rate of uveal melanoma-related metastasis
on the basis of individual tumor cytogenetic profile. DESIGN: Retrospective case
series. PARTICIPANTS: A total of 1059 patients with uveal melanoma. METHODS: Fine
needle aspiration biopsy (FNAB) for DNA amplification and whole genome array
based assay were performed for analysis of chromosomes 3, 6, and 8. MAIN OUTCOME
MEASURES: Melanoma-related metastasis. RESULTS: The mean patient age was 57
years, and most were white (1026/1059, 97%). The melanoma involved the choroid
(938/1059, 89%), ciliary body (85/1059, 8%), or iris (36/1059, 3%), with 19%
being macular in location. The mean largest basal diameter was 11 mm (median, 12
mm; range, 3-24 mm), and mean thickness was 5 mm (median, 4 mm; range, 1-20 mm).
On the basis of individual chromosomal mutations, risk for metastasis was
increased for chromosome 3 partial monosomy (hazard ratio [HR], 2.84; P = 0.001),
3 complete monosomy (HR, 6.7, P < 0.001), 6q loss (HR, 3.1, P = 0.003), 8p loss
(HR, 21.5, P < 0.001), and 8q gain (HR, 9.8, P < 0.001). Kaplan-Meier estimate
for melanoma-related metastasis in 1, 3, 5, and 7 years for 3 partial monosomy
was 1%, 5%, 14%, and 17%; for 3 complete monosomy was 3%, 19%, 28%, and 37%; for
6q loss was 8%, 23%, 49%, and 49%; for 8p loss was 8%, 29%, not estimable (NE),
and NE; and for 8q gain was 6%, 21%, 35%, 48%, respectively. On the basis of
personalized cytogenetic profiles, Kaplan-Meier estimates (1, 3, and 5 years) for
melanoma-related metastasis for 3, 6, and 8 disomy (1%, 1%, 4% [HR, 1]) were low
compared with the higher-risk combinations of 3 complete monosomy, 6p gain, and
8q gain (0%, 29%, 29% [HR, 10.6, P = 0.02]); 3 complete monosomy, 6 disomy, 8q
gain, and 8p gain (14%, 14%, NE [HR, 18.3, P = 0.02]); 3 complete monosomy, 6
disomy, and 8q gain (8%, 27%, 39% [HR, 19.5, P < 0.001]); and 3 complete
monosomy, 6 disomy, 8q gain, and 8p loss (3%, 28%, NE [HR, 31.6, P < 0.001]),
respectively. CONCLUSIONS: Risk for melanoma-related metastasis strongly
correlates with personalized cytogenetic profiles, with 5-year Kaplan-Meier
estimates ranging from 4% with chromosomes 3, 6, and 8 disomy up to 39% for 3
complete monosomy, 6 disomy, and 8q gain.
PMID- 28495153
TI - The next chapter in malaria eradication.
PMID- 28495154
TI - The prescribing cascade revisited.
PMID- 28495155
TI - Making sense of polycystic kidney disease.
PMID- 28495156
TI - Offline: Is the NHS in crisis?
PMID- 28495157
TI - Concern over India's move to cut funds for PHFI.
PMID- 28495158
TI - Frontline: Providing care in the midst of the crisis in Yemen.
PMID- 28495159
TI - Health care in Turkey in the Erdogan era.
PMID- 28495160
TI - Who is responsible for the health care of refugees?
PMID- 28495161
TI - Early use of the microscope.
PMID- 28495162
TI - Mortality decrease according to socioeconomic groups.
PMID- 28495163
TI - Mortality decrease according to socioeconomic groups.
PMID- 28495164
TI - Steroid withdrawal and bone disease after kidney transplantation.
PMID- 28495165
TI - Mortality decrease according to socioeconomic groups - Authors' reply.
PMID- 28495166
TI - Steroid withdrawal and bone disease after kidney transplantation - Authors'
reply.
PMID- 28495167
TI - Bioresorbable vascular scaffolds and late lumen loss.
PMID- 28495168
TI - Bioresorbable vascular scaffolds and late lumen loss - Authors' reply.
PMID- 28495169
TI - An error of omission in the report on the clinical trial scene in India.
PMID- 28495170
TI - Targeted enrichment sequencing in two midterm pregnancies with severe
abnormalities on ultrasound.
PMID- 28495171
TI - Tailored genetic testing provides answer to fetal anomaly.
PMID- 28495172
TI - Cysteine cathepsins B and X promote epithelial-mesenchymal transition of tumor
cells.
AB - Cathepsins B and X are lysosomal cysteine carboxypeptidases suggested as having a
redundant role in cancer. They are involved in a number of processes leading to
tumor progression but their role in the epithelial-mesenchymal transition (EMT)
remains unknown. We have investigated the contribution of both cathepsins B and X
in EMT using tumor cell lines differing in their expression of epithelial and
mesenchymal markers and cell morphology. Higher levels of both cathepsins are
shown to promote EMT and are associated with the mesenchymal-like cell phenotype.
Moreover, simultaneous knockdown of the two peptidases triggers a reverse,
mesenchymal to epithelial transition. Of the two cathepsins, cathepsin B appears
to be the stronger promotor of EMT. Furthermore, we evaluated the involvement of
cathepsin B and X in the transforming growth factor-beta1 (TGF-beta1) signaling
pathway, one of the key signaling mechanisms triggering EMT in cancer. In MCF-7
cells the expression of cathepsin B was shown to depend on their activation with
TGF-beta1 while, for cathepsin X, a TGF-beta1 independent mechanism of induction
during EMT is indicated. EMT is thus shown to be another mechanism linking
cathepsins B and X with tumor progression. With silencing of their expression or
inhibition of enzymatic activity, the tumor cells could be reverted to less
aggressive epithelial-like phenotype.
PMID- 28495173
TI - Late treatment of obstetrical brachial plexus palsy by humeral rotational
osteotomy and lengthening with an intramedullary elongation nail.
AB - To date, all the authors who have recommended external rotation osteotomy (ERO)
in the late treatment of obstetrical brachial plexus palsy (OBPP), have neglected
upper limb length discrepancy, which is an another sequelae of OBPP. In this
paper, a new technique is reported for the late treatment of OBPP patients with
upper limb length discrepancy, in which both humeral external rotation osteotomy
(ERO) and lengthening are applied with an intramedullary elongation nail. With
this technique, upper limb function is improved through re-orientation of the
shoulder arc to a more functional range, and further improvements will be seen in
the appearance of the upper limb with the elimination of length discrepancy. It
is also advocated that there is a potentiating effect of the humeral lengthening
on shoulder movements gained by ERO when the osteotomy is applied above the
deltoid insertion, as this allows more lateralized placement of the deltoid
insertion.
PMID- 28495174
TI - PPARgamma-mediated G-protein coupled receptor 120 signaling pathway promotes
transcriptional activation of miR-143 in adipocytes.
AB - MicroRNAs (miRNAs), the small noncoding RNAs, regulate various biological
processes such as adipogenesis. MicroRNA-143 (miR-143) promotes adipocyte
differentiation, and is correlated with obesity in mice fed a high-fat diet.
However, the transcriptional regulation of miR-143 is largely unknown. In this
study, we identified that miR-143 is a target of peroxisome proliferator
activated receptor gamma (PPARgamma), a key transcription factor in adipogenesis.
Four putative peroxisome proliferator response elements (PPREs) were identified
in the miR-143 promoter region. Using chromatin immune-precipitation, we observed
that PPARgamma was bound with two PPRE regions of the miR-143 promoter in 3T3-L1
adipocytes. A luciferase reporter assay showed that the PPRE1 region (-1330/
1309) of the miR-143 promoter played an important role in PPARgamma
transcriptional activation. In addition, we determined that G-protein coupled
receptor 120 (GPR 120), which functions as an omega 3 fatty acid receptor,
affected miR-143 expression in adipocytes. GPR120 silencing in adipocytes
inhibited the expression of PPARgamma and miR-143, whereas GPR120 overexpression
led to increased expressions of PPARgamma and miR-143. Silencing of PPARgamma
inhibited the induction of miR-143 by GPR-120. These results suggested that a
PPARgamma-mediated GPR120 signaling pathway promotes transcriptional activation
of miR-143 in adipocytes.
PMID- 28495175
TI - A case of ureteric polypoid endometriosis presenting in a post-menopausal woman.
PMID- 28495176
TI - Pubertal Timing and Cardiometabolic Markers at Age 16 Years.
AB - OBJECTIVE: To examine the association between pubertal timing and cardiometabolic
markers among adolescents. STUDY DESIGN: We used data from Dutch adolescents
participating in a birth cohort study. The study population for the current study
consisted of 799 adolescents of whom data were available for at least 1 of the
exposure variables (pubertal timing and/or age at menarche) and any of the
cardiometabolic markers (waist circumference, cholesterol, blood pressure [BP],
glycated hemoglobin) measured at age 16 years. Adolescents self-reported pubertal
development at ages 11, 14, and 16 years. We categorized participants with early
(84 girls, 88 boys), intermediate (240 girls, 211 boys), or late pubertal timing
(89 girls, 85 boys). We estimated differences in cardiometabolic markers using
linear regression analysis. RESULTS: Girls with early pubertal timing had 1.54 cm
larger waist circumference (95% CI .05; 3.03) and 3.98 mm Hg higher systolic BP
(95% CI 1.69; 6.27) at age 16 years than girls with intermediate pubertal timing.
The association with systolic BP remained after adjusting for childhood body mass
index (BMI) (age 8 years) but attenuated after adjusting for BMI in adolescence
(age 16 years). Boys with early pubertal timing had 0.79 mmol/mol lower glycated
hemoglobin (95%CI -1.38; -0.20) than boys with intermediate pubertal timing.
CONCLUSIONS: Girls with early pubertal timing had unfavorable BP levels at age 16
years, independent of BMI in childhood. Girls and boys with late pubertal timing
had a tendency for lower waist circumference, but no differences in other
cardiometabolic markers. Late pubertal timing does not appear to be a risk factor
for unfavorable cardiometabolic markers in adolescence.
PMID- 28495177
TI - Three-Month Old with a Tongue Mass.
PMID- 28495178
TI - Transurethral resection of ejaculatory ducts: a step-by-step guide.
AB - OBJECTIVE: To demonstrate the key components for completing a successful
transurethral resection of ejaculatory ducts (TURED) for completely obstructed
ejaculatory ducts (EDs). DESIGN: Video presentation. SETTING: University
Hospital. PATIENT(S): A 40-year-old man presenting with primary infertility and
abnormal semen analysis (pH 6.4, volume of 0.7 cc, concentration 16 million/cc,
and 7% motility) in whom a transrectal ultrasonography revealed dilated seminal
vesicles measuring more than 1.5 cm and seminal vesicle aspiration detected no
sperm in the aspirate. INTERVENTION(S): Transurethral resection of ejaculatory
ducts. MAIN OUTCOME MEASURE(S): Intraoperative technique with commentary
highlighting tips for a successful TURED. RESULT(S): This video provides a step
by-step guide for TURED, including transrectal ultrasonography-guided seminal
vesicle puncture for instillation of methylene blue to allow more precise
identification of EDs. Vesiculography was performed near the end of the procedure
to assess for patency of EDs and confirm both sides had been opened.
(Institutional review board approval was obtained for this presentation.)
CONCLUSION(S): The key portions for performing a successful TURED includes
seminal vesicle instillation of methylene blue for easier identification of EDs.
Vesiculography is performed near the end of the procedure to ensure both EDs have
been opened as well as to assess for passive drainage of the seminal vesicles
through the newly open EDs.
PMID- 28495179
TI - Impact of Hypertriglyceridemia on Carotid Stenosis Progression under Normal Low
Density Lipoprotein Cholesterol Levels.
AB - BACKGROUND: Dyslipidemia is a well-known risk factor for carotid stenosis
progression, but triglycerides have attracted little attention. The aim of this
study was to assess if serum triglycerides affect progression of carotid stenosis
in patients with well-controlled low-density lipoprotein cholesterol (LDL-C)
levels. METHODS: This is a retrospective study in a single hospital consisting of
71 Japanese patients with internal carotid artery stenosis greater than or equal
to 50% and normal serum LDL-C levels who underwent angiographic examination with
or without the resultant carotid artery stenting or endarterectomy from 2007 to
2011, and were subsequently followed up for 4 years. Clinical factors including
fasting serum triglyceride values were compared between the progression (>=10%
increase in degree of carotid stenosis on ultrasonography) and the nonprogression
groups. RESULTS: During 4 years, 15 patients (21.1%) had carotid stenosis
progression on either side. Cox regression analysis demonstrated that symptomatic
cases (hazard ratio [HR], 4.327; P = .019), coexisting intracranial
arteriosclerotic stenosis (HR, 5.341; P = .005), and hypertriglyceridemia (HR,
6.228; P = .011) were associated with subsequent progression of carotid stenosis.
Kaplan-Meier plots demonstrated that the progression-free survival rate was
significantly higher in patients without hypertriglyceridemia and intracranial
arteriosclerotic stenosis at baseline. CONCLUSIONS: Among patients with moderate
to severe carotid stenosis and well-controlled LDL-C, hypertriglyceridemia was an
important risk factor for progression of carotid stenosis irrespective of
surgical treatments. It would be worthwhile to test if triglyceride-lowering
medications suppress carotid stenosis progression.
PMID- 28495180
TI - Conicity index: An anthropometric measure to be evaluated.
PMID- 28495181
TI - Assessment of left ventricular function with tissue Doppler echocardiography and
of B-type natriuretic peptide levels in patients undergoing transcatheter aortic
valve implantation.
AB - INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is an emerging
minimally invasive treatment modality in high surgical risk or inoperable
patients. AIM: The aim of this study was to ascertain the effect of TAVI on left
ventricular (LV) systolic and diastolic function and serum B-type natriuretic
peptide (BNP) levels in high surgical risk or inoperable patients with severe
aortic stenosis. METHODS: Fifty-five patients were included in our retrospective
study. LV systolic and diastolic function was assessed with conventional and
tissue Doppler imaging (TDI) prior to and after TAVI. Additionally, BNP was
measured 24 h before and three months after the procedure. Echocardiographic
controls were performed at one, three and six months and one year and mean values
were taken. At the end of the study, LV systolic and diastolic function, serum
BNP levels and New York Heart Association functional capacity were assessed and
compared to baseline parameters. RESULTS: The TAVI procedure was successful in
all patients. In-hospital mortality was 1.8% (one patient). There was a
substantial improvement in LV function and functional capacity at follow-up. In
addition, a statistically significant decrease was detected in serum BNP levels
post-TAVI (median 380 pg/ml [176.6-929.3] vs. 215 pg/ml [96.0-383.0], p=0.0001).
Only one patient required a permanent pacemaker (1.8%) and there was no mortality
after TAVI during follow-up. There were significant increases in LV ejection
fraction and aortic valve area (51.0+/-13.1% vs. 58.4+/-9.1%, p<0.001, and 0.6+/
0.1 cm2 vs. 2.1+/-0.2 cm2, p=0.0001, respectively). At the end of the study,
conventional Doppler echocardiography revealed improvement in diastolic function,
with an increase in mitral E wave, a decrease in mitral A wave and an increase in
E/A ratio. Deceleration time and isovolumetric relaxation time were shortened and
myocardial performance (Tei) index decreased. TDI showed an increase in systolic
myocardial velocity (Sm) and early diastolic velocity (Em). Septal mitral annular
Sm and Em were increased, whereas MPI was reduced. CONCLUSION: We found that LV
structural changes and diastolic dysfunction occur in patients with severe aortic
stenosis and that TAVI is able to reverse these abnormalities, which we
demonstrated by both conventional echocardiography and TDI. In addition, serum
BNP levels were decreased after TAVI.
PMID- 28495182
TI - Threats to internal validity in renal sympathetic denervation trials.
PMID- 28495183
TI - IDF Clinical Practice Recommendation on the Diabetic Foot: A guide for healthcare
professionals.
PMID- 28495184
TI - Interleukin-1beta as emerging therapeutic target in hematological malignancies
and potentially in their complications.
AB - Interleukin-1beta (IL-1beta) is a pleiotropic cytokine that exerts multiple roles
in both physiological and pathological conditions. It is produced by different
cell subsets, and drives a wide range of inflammatory responses in numerous
target cells. Enhanced IL-1beta signaling is a common event in patients of
hematological malignancies. Recent body of evidence obtained in preclinical
models shows the pathogenic role of these alterations, and the promising
therapeutic value of IL-1 targeting. In this review, we further highlight a
potential contribution of IL-1beta linking to complications and autoimmune
disease that should be investigated in future studies. Hence, drugs that target
IL-1 may be helpful to improve outcome or reduce morbidity in patients. Some of
them are FDA-approved, and used efficiently against autoimmune diseases, like IL
1 receptor antagonist. In the clinic, however, this agent seems to have limited
properties. Current improved drugs will allow to determine the true potential of
IL-1 and IL-1beta targeting as therapy in hematological malignancies and their
related complications.
PMID- 28495185
TI - Association of circulatory asymmetric dimethylarginine (ADMA) with diabetic
nephropathy in Asian Indians and its causative role in renal cell injury.
AB - AIM: Asymmetric dimethylarginine (ADMA) is involved in the regulation of nitric
oxide synthesis and in the maintenance of vascular tone and structure. But the
role and status of ADMA in diabetes induced kidney injury is not clear. Hence
this study is investigating the role of ADMA in the progression of kidney injury
and its circulatory status in Asian Indians with and without diabetic
nephropathy. METHODS: Recruited study subjects were divided into normal glucose
tolerance (NGT), type 2 diabetes mellitus (T2DM) and T2DM with micro or
macroalbuminuria. Albuminuria was calculated using urinary albumin and creatinine
ratio (UACR). ADMA was measured using ELISA. Kidney cell damage in terms of
fibrotic markers and ADMA metabolism in terms of DDAH activity were investigated
in kidney fibroblasts and mesangial cells. RESULTS: There was a significant
elevation in plasma ADMA levels in micro and macroalbuminuric diabetic patients.
We found a significant positive correlation between ADMA and UACR, serum
creatinine, HbA1C and fasting plasma glucose. A cut-off value of ADMA, 0.666MUM/l
had a sensitivity and specificity of 70.0% and 65.6%, respectively for detecting
diabetic nephropathy. DDAH activity was significantly decreased and fibrotic
markers such as fibronectin and alpha-SMA were significantly increased upon high
glucose and ADMA treatment. CONCLUSION: We are suggesting a causative role of
ADMA in the development of kidney injury in terms of renal fibrosis and also a
cut point of 0.666MUM/l of plasma ADMA level appears to be a predictive risk
threshold for diabetic nephropathy in south Asian Indian population.
PMID- 28495186
TI - Puerperal uterine inversion from two viewpoints: Its recurrence at the next
pregnancy and "unavoidable"-procedure-associated inversion.
PMID- 28495187
TI - Comment on "Potentized estrogen in homeopathic treatment of endometriosis
associated pelvic pain: A 24-week, randomized, double-blind, placebo-controlled
study".
PMID- 28495188
TI - Comparison of two environmental sampling tools for the detection of Clostridium
difficile spores on hard bathroom surfaces in the hospital setting.
PMID- 28495189
TI - Genetic analysis of Rhipicephalus sanguineus sensu lato ticks parasites of dogs
in Africa north of the Sahara based on mitochondrial DNA sequences.
AB - The aim of this work was to determine the evolutionary relationship among tick
populations of Rhipicephalus sanguineus sensu lato distributed in Africa north of
the Sahara and different lineages of R. sanguineus s.l. distributed in different
regions of Sub-Saharan Africa, America and Europe through the analysis of DNA
sequences of two mitochondrial genes. One hundred and thirty six 16S rRNA gene
sequences and twenty-seven 12S rRNA gene sequences of R. sanguineus s.l. were
analyzed. Phylogenetic analyses were performed including different lineages of R.
sanguineus s.l. from America, Europe and Africa, and species belonging to the R.
sanguineus group as Rhipicephalus camicasi, Rhipicephalus guilhoni, Rhipicephalus
sulcatus, Rhipicephalus rossicus, Rhipicephalus pusillus, Rhipicephalus turanicus
and Rhipicephalus leporis. At least two different lineages of R. sanguineus s.l.
are living in sympatry in Africa north of the Sahara. One of these mitochondrial
lineages belongs to the same evolutionary entity that R. sanguineus s.l. from
tropical areas of America, R. sanguineus s.l. from Sub-Saharan Africa, R.
camicasi and R. guilhoni. The other mitochondrial lineage of R. sanguineus s.l.
present in Africa north of the Sahara is phylogenetically associated to R.
sanguineus s.l. ticks from southeastern Europe (Romania, Turkey and Greece). Both
evolutionary entities are clearly different to the evolutionary entity formed by
R. sanguineus s.l. from western Europe and temperate areas of America. Thus, the
name R. sanguineus s.s. cannot be assigned to any of the two evolutionary
entities present in Africa north of the Sahara. The taxonomic status of these
taxa will remain unresolved until new lines of evidence become available to
complement the current results based on mitochondrial DNA.
PMID- 28495190
TI - Antibodies to Toxoplasma gondii and Leishmania spp. in domestic cats from Luanda,
Angola.
AB - Toxoplasma gondii and Leishmania spp. are zoonotic protozoa of importance to
animal and public health. The present study aimed to assess for the first time
the seroprevalence of these zoonotic parasites in a domestic feline population
living in Luanda, Angola. One hundred and two cats were sampled at a veterinary
medical centre, from May 2014 to February 2016. The age of the cats ranged from
2.5 to 143 months (median: 12 months; interquartile range: 7.5-24). Serum samples
were tested for immunoglobulin (Ig) G antibodies to T. gondii at two-fold
dilutions of 1:20 to 1:2560 with a modified agglutination test (MAT) commercial
kit. The direct agglutination test (DAT) for titration of IgG antibodies specific
to Leishmania spp. used a standard freeze-dried antigen at a concentration of
5*107 promastigotes per milliliter, following a predefined protocol. Two-fold
dilution series ranging from 1:25 to 1:800 were tested, with a cut-off titre of
100 chosen for seropositivity. Four out of 102 cats (3.9%; 95% confidence
interval [CI]: 1.1-9.7) had antibodies to T. gondii: one had a titer of 20, one a
titer of 160, and two had a titer>=2560. No cat (0.0%; CI: 0.0-3.5) was found
seropositive for Leishmania spp. A statistically significant difference was found
between T. gondii seroprevalence and Leishmania spp. seroprevalence (p=0.043).
The odds of a cat being seropositive to T. gondii increased by an average factor
of 1.58 for each 1-year increase in age (p=0.003). The sampled cats were well
cared animals and may not represent the overall feline population of Angola at
the national and city levels. The fact that only 12 out of the 102 sampled cats
ate or had access to raw or undercooked meat and/or viscera may have reduced the
likelihood of finding seropositive results. Under these circumstances, additional
studies, including a larger number of cats, are necessary for a more
comprehensive assessment of the zoonotic risk posed by these animals in Angola.
PMID- 28495191
TI - Review on the immunological and molecular diagnosis of neosporosis (years 2011
2016).
AB - Neosporosis, caused by the apicomplexan protozoan Neospora caninum, is a disease
which affects a wide range of mammalian hosts (mainly cattle and dogs). N.
caninum infection is considered the major cause of livestock abortions worldwide,
and therefore is responsible for great losses in the industry. Because there are
no effective treatments or vaccines, diagnosis is essential for pathogen control.
Studies of N. caninum mechanisms of pathogenesis have led to the identification
of new antigens, including NcSRS2, NcSAG1, Ncp40, NcSUB1, NcMIC10, and NcGRAs;
and a variety of molecular and immunological assays, based on these molecules,
have been proposed to detect N. caninum in tissues or serum samples. We report
advances achieved in the last five years in neosporosis control, based on the
immunological and molecular diagnostic tests.
PMID- 28495192
TI - Effect of creep-fed supplement on the susceptibility of pasture-grazed suckling
lambs to gastrointestinal helminths.
AB - This study evaluated the effect of creep feeding a protein supplement on the
susceptibility of suckling lambs to infection with gastrointestinal helminths.
Male and female lambs were grazed on Brachiaria spp. pastures next to their
mothers. Animals were allocated to one of two treatments: creep feeding (261g/d)
and control (no supplementation). The trial period was the suckling of lambs
during two years of study: May-October 2013 and March-July 2014. Supplementary
creep feeding of lambs improved animal performance (P<0.05). Creep-fed lambs
reached 18kg body weight in 64 d, but unsupplemented lambs required 77 d to reach
the same weight. Lambs were susceptible to helminth infection during lactation;
lambs in both treatments had high fecal egg counts (FECs), with means >1000 eggs
per gram, as early as 45days of age, when the daily grazing time per animal
increased. Creep feeding reduced the FECs of suckling lambs >60days of age in
infections dominated by Haemonchus contortus. Totals of 20 and 48 anthelmintic
treatments were administered to the supplemented and unsupplemented animals,
respectively. The effect of this variable, however, was significant (P<0.05) only
after 60days, when nine and 28 treatments had been administered to the
supplemented and unsupplemented lambs, respectively. The number of strongyloid
larvae recovered from the paddock did not differ significantly (P >0.05) between
the two treatments, indicating similar challenges by infective larvae to both
groups. The supplementation of lambs by creep feeding can thus be a strategy for
the sustainable control of helminth infection, because it reduces the dependence
on anthelmintic treatment.
PMID- 28495193
TI - First genetic characterization of Toxoplasma gondii in stray cats from Algeria.
AB - Toxoplasmosis is a parasitic disease with worldwide distribution and a major
public health problem. In Algeria, no data are currently available about
genotypes of Toxoplasma gondii isolated from animals or humans. The present study
assesses for the first time the seroprevalence of toxoplasmosis in stray cats,
and provides molecular characterization of T. gondii strains circulating in this
feline population in Algiers, the capital city of Algeria. Sera from 96 stray
cats were tested for the presence of antibodies against T. gondii using the
modified agglutination test. The seroprevalence was 50% (48/96) using 1:6 as the
positivity cut-off. Different organs samples from stray cats, including heart
samples, were tested for the presence of Toxoplasma DNA using real-time PCR. T.
Gondii DNA was detected in 90.6% (87/96) of hearts. Of these parasitic DNAs, 22
were submitted to genotyping through the analysis of 15 microsatellite markers.
The identified genotypes (12 of 22) mainly belonged to the type II lineage.
PMID- 28495194
TI - Neospora caninum abortion in a Malayan tapir (Tapirus indicus).
AB - A captive 17-year old female Malayan tapir (Tapirus indicus) aborted a fetus with
a crown rump length of 19cm in early pregnancy. The fetus showed an early state
of mummification. Histologically, a multifocal mononuclear encephalitis,
myocarditis and periportal hepatitis was present indicating a possible protozoal
cause of abortion. Although immunohistologically, Neospora (N.) caninum antigen
could not be demonstrated, N. caninum DNA was detected by Polymerase Chain
Reaction (PCR) in brain, heart, liver and lung of the fetus. N. caninum DNA was
extracted from the aborted fetus and the microsatellite marker MS10 was amplified
by PCR and sequenced. The obtained MS10 microsatellite pattern has not been
described in Germany yet. Nevertheless, the MS10 pattern was very similar to
those reported for N. caninum isolated from dogs and cattle in Germany. Because
of the histological pattern and extent of the lesions, neosporosis was suspected
as the cause of fetal death and abortion. This case report describes for the
first time transplacental transmission of N. caninum and abortion due to
neosporosis in a tapir.
PMID- 28495195
TI - In vitro repellency of DEET and beta-citronellol against the ticks Rhipicephalus
sanguineus sensu lato and Amblyomma sculptum.
AB - Rhipicephalus sanguineus sensu lato and Amblyomma sculptum can parasite humans
and domestic animals and are vectors of pathogens, including zoonoses. Repellents
are an important tool of tick control. This study aimed to compare the efficacy
of N,N-diethyl- 3-methylbenzamide (DEET), a standard repellent, versus beta
citronellol in a Petri dish bioassay. A semicircle of filter paper (31.8cm2) was
treated with 87MUl of one of four concentrations (0.200, 0.100, 0.050 and
0.025mg/cm2) of beta-citronellol, DEET or solvent (ethanol). A head-to-head test
was developed treating one side with increasing concentrations of beta
citronellol as above mentioned, against the highest concentration of DEET.
Besides that a blank assay was performed. Three males and three females were
placed in the middle of the plate and their location was evaluated 5, 10 and
30min after the test was initiated. As a result, the time had no significant
effect on repellency response of the ticks exposed to both compounds and their
concentrations. The repellency response raised according with the increase of
concentration. Additionally, our findings indicate that the tick A. sculptum was
more sensitive to the compounds tested and beta-citronellol showed a higher
efficacy than DEET. In addition, beta-citronellol could be formulated to protect
humans and other animals from R. sanguineus s. l. and A. sculptum infestation, as
well as the diseases transmitted by these species.
PMID- 28495196
TI - Pharmacokinetics of a novel spot-on formulation of praziquantel for dogs.
AB - Praziquantel (PZQ) is an anthelmintic drug used both in humans and animals that
can be administered through various routes. There are transdermal formulations
for cats, but only oral or subcutaneous dosage forms for dogs. Given the fact
that the cat's skin and the dog's skin have different characteristics, which in
turn affect bioavailability, we developed a PZQ spot-on formulation for dogs.
This study was aimed at determining the plasmatic behavior of topically
administered PZQ (Labyes(r)) in adult dogs. Dogs were administered PZQ (14.5mg/kg
PZQ, from a solution of 100mg/ml). Blood samples were drawn before treatment
onset and at the following time points after PZQ administration: 1, 2, 4, 6, 12,
24 and 48h. PZQ plasma concentration was determined by ultra-high performance
liquid chromatography (UPLC) coupled to tandem mass spectrometry (MS/MS).
Observed maximum concentration (Cmax), area under the concentration-time curve
from the time of drug administration to infinity (AUCinf) and time to maximum
concentration (Tmax) were calculated for each animal, and mean+/-SD for each
parameter was obtained. Results were as follows: Cmax=56.0+/-15ng/ml;
AUCinf=910.2+/-220ng*h/ml, Tmax=5.0+/-1.1h. This is the first study to provide
pharmacokinetic data of a praziquantel spot-on formulation for dogs.
PMID- 28495197
TI - Randomized, allopurinol-controlled trial of the effects of dietary nucleotides
and active hexose correlated compound in the treatment of canine leishmaniosis.
AB - First-line treatment for canine leishmaniosis (CanL) is N-methylglucamine
antimoniate (MGA) combined with allopurinol. However, in some dogs allopurinol
may induce hyperxanthinuria leading to urolithiasis. Moreover, allopurinol
resistance has recently been described in Leishmania infantum isolates from
treated dogs with a relapse of the disease. Alternative treatments are thus
needed. Since the type of host immune response strongly influences CanL
progression and prognosis, dogs could benefit from treatments targeted at
modulating such response, such as nucleotides and active hexose correlated
compound (AHCC). The aim of this study was to evaluate the effects of an oral
combination of nucleotides and AHCC in dogs with clinical leishmaniosis. Sixty
nine dogs with naturally-occurring clinical leishmaniosis were included in this
multicenter, open-label, positively-controlled clinical trial and randomized to
receive 10mg/kg allopurinol PO BID (allopurinol group) or 17mg/kg AHCC plus
32mg/kg nucleotides PO SID (supplement group) for 180 days. All dogs were also
given 50mg/kg MGA SC BID during the first 28 days. At the time points 0, 30, and
180 days of the trial, dogs underwent a clinical examination, and blood, urine,
and bone marrow samples were submitted for analytical tests. Final data analyses
(allopurinol group: n=29; supplement group: n=24) revealed a significant
improvement in both groups in clinical scores and ELISA-determined antibody
titers after treatment. However, the supplement group showed a significantly
lower clinical score (P=0.005) and significantly higher antibody titers (P=0.032)
after 180 days, compared to the allopurinol group. RT-PCR parasite loads were
reduced in groups (mean+/-SD supplement: 0.38+/-0.56 vs 5.23+/-18.9; allopurinol:
0.45+/-1.47 vs 3.09+/-8.36 parasites/ng of DNA), but there were no significant
differences over time or between groups. During the study, 12 dogs in the
allopurinol group developed xanthinuria (41%) compared to no dogs (0%) in the
supplement group (P=0.000). Both treatments led to significantly increased
CD4+/CD8+ ratio, and improvements in protein electrophoretic pattern and acute
phase response. In conclusion, 6-month oral treatment with nucleotides and AHCC
in addition to MGA showed similar efficacy to the current first-line treatment
for CanL, without producing xanthinuria. This combination could be a good
alternative to MGA-allopurinol combination treatment for CanL, especially for
dogs suffering allopurinol-related adverse events.
PMID- 28495198
TI - Phenotypic expression of parasite susceptibility to Haemonchus contortus in
Pelibuey sheep.
AB - The objective of this study was to determine if the mean faecal egg count (FEC)
from a first experimental Haemonchus contortus infection could be used to
classify parasite-naive Pelibuey hair sheep as parasite-resistant high responders
and parasite-susceptible low responders. Twenty 6- to 7-month-old Pelibuey male
sheep raised free of gastrointestinal nematodes were challenged with 7500+/-1412
H. contortus L3 larvae administrated orally on day 0 of the study. Faecal samples
from each lamb were obtained daily from 21 to 41days post-infection (Stage I).
Lambs received a second artificial infection of 8420+/-1545L3 larvae on day 42,
with faecal samples collected from day 65 to day 78 (Stage III). The mean FEC for
each lamb in Stage I was used to classify 8 lambs with means for FEC that were
more than two standard errors (SE) below the overall mean (i.e., <4764 eggs per
gram of feces; epg) as high responders. The remaining 12 lambs were classified as
low responders. Means for FEC in Stage I were 2449+/-194 epg for high responders
and 14,461+/-1044 epg for low responders (P<0.05). High responders also had lower
FEC than low responders in Stage III (actual means of 650+/-220 vs. 5933+/-1990
epg; P<0.05 following log transformation to normalize the FEC distribution).
Lambs were then reclassified as high and low responders based on their mean FEC
in Stage III. Fourteen lambs with means for FEC that were more than one standard
error (SE) below the overall mean (i.e., below 1537 epg) were classified as high
responders. The remaining six lambs were classified as low responders. Use of the
Stage I responder class to predict the Stage III responder class resulted in an
83.3% sensitivity but only a 50% specificity. The positive predictive value was
41.7% and the negative predictive value was 87.5%. The poor positive predictive
value was caused by 5 animals with high FEC in Stage I, but low FEC in Stage III.
The first infection thus identified most high-responder lambs, but a second
infection may improve accuracy by separating lambs with an intermediate level of
resistance from truly susceptible lambs. This protocol now requires additional
validation under more practical conditions involving natural parasite infections
and larger lamb numbers.
PMID- 28495199
TI - An automated, multiplex-tandem PCR platform for the diagnosis of gastrointestinal
nematode infections in cattle: An Australian-European validation study.
AB - Detecting the genera and species of gastrointestinal (GI) nematode infections in
faecal samples obtained from cattle requires the incubation of faeces ('larval
culture') followed by identification of the third-stage larvae that are harvested
after 10-14days. Substantial research in the development of PCR-based methods for
the rapid and specific identification GI nematodes has been conducted for small
ruminants, whilst only few such assays have been developed for cattle. In the
present paper we describe the development of an automated, robotic PCR platform
for the detection and genus and/or species-specific identification of GI
nematodes from bovine faecal samples. This test was then validated using samples
from different regions of three countries (Australia, Belgium and Scotland). The
PCR platform was found to be highly sensitive and specific for the identification
of the important GI nematodes in naturally infected cattle (both estimates >90%).
The PCR platform can also estimate the percentage of genera or species present in
a mixed-species infection, and was found superior to larval culture in terms of
speed (1-2days versus 1-2 weeks for culture), sensitivity and specificity. The
PCR was simple to use and the operator requires no knowledge or experience to
identify the nematodes present, compared to larval culture where even experienced
operators can make substantial errors due to considerable overlap in the
published characteristics of key species.
PMID- 28495200
TI - Genotyping of Theileria lestoquardi from sheep and goats in Sudan to support
control of Malignant Ovine Theileriosis.
AB - Theileriosis, caused by parasitic protozoa of the genus Theileria parasites, are
among the major tick-borne diseases of ruminant livestock. The largest economic
losses are attributed in particular to those caused by the leukoproliferative
species of Theileria: T. parva, T. annulata and T. lestoquardi. Theileria
lestoquardi is transmitted by Hyalomma ticks and causes malignant ovine
theileriosis (MOT), a disease that is particularly prevalent in Sudan. The
disease is considered of a high economic importance in Sudan, where export of
sheep is a major component of the national economy. A live vaccine based on a
Sudanese isolate of T. lestoquardi (Atbara strain) was previously developed for
the control of MOT in Sudan, but not yet deployed in the field. The present study
aims to genetically characterize and compare samples of T. lestoquardi
circulating in Sudan as well as the live vaccine isolate in order to understand
vaccine breakthroughs and failure that may occur. Sheep and goats blood samples
were collected from six regions in Sudan that are known to be endemic for T.
lestoquardi infection or have experienced outbreaks of MOT. Blood samples
infected with T. lestoquardi were identified by PCR or RLB. Genotyping was
carried out by (1) sequencing the homologues of two T. parva CD8+ T cell antigen
genes, Tp1 and Tp2, and (2) using a panel of seven micro- and mini-satellite
markers. A total of 100 T. lestoquardi positive field samples and the T.
lestoquardi (Atbara) vaccine were genotyped. The results showed that all samples
had mixed genotypes, with several alleles identified at one or more loci. The
gene diversity ranged from 0.7840 (TS8) to 0.2133 (TS12) with mean values of
0.5470. PCA revealed three clusters of the parasite in Sudan; interestingly one
independent cluster was clearly seen, corresponding to the vaccine isolate. The
T. lestoquardi Tp1 homologue showed higher homology with T. annulata than with T.
parva sequences included the defined single CD8+ T cell target epitope region.
The result indicates that multiple genotypes are a common feature of T.
lestoquardi infection in Sudan. Both genotyping and the sequencing results
clearly showed that the vaccine isolate is highly distinct from the field
samples. This finding raised the question whether vaccination with the prepared
lived vaccine will effectively protect animals against challenges by the field
isolates of T. lestoquardi. The results of this work will inform on the best
approach for controlling MOT in Sudan.
PMID- 28495201
TI - Self-reported balance status is not a reliable indicator of balance performance
in adolescents at one-month post-concussion.
AB - OBJECTIVES: To determine if self-reported balance symptoms can be used as a proxy
for measures of the center of pressure (COP) to identify balance deficits in a
group of concussed adolescents. DESIGN: Case-control. METHODS: Thirteen
adolescents 1-month post-concussion who reported ongoing balance problems
(Balance+), 20 adolescent 1-month post-concussion who reported no balance
problems (Balance-), and 30 non-injured adolescents (control) completed a series
of balance tests. Participants completed two 2-min trials standing on a Nintendo
Wii Balance BoardTM during which the COP under their feet was recorded: i) double
leg stance, eyes open; ii) double-leg stance, eyes closed. Participants also
completed a dual-task condition combining a double-leg stance and a Stroop Colour
word test. RESULTS: Participants in both the Balance+ and Balance- group swayed
over a larger ellipse area compared to the control group while completing the
Eyes Closed (Balance+, p=0.002; Balance-, p=0.002) and Dual-Task (Balance+,
p=0.001; Balance-, p=0.004) conditions and performed the Dual-Task condition with
faster medio-lateral velocity (Balance+, p=0.003; Balance-, p=0.009). The
participants in the Balance- group also swayed over a larger ellipse area
compared to the control group while completing the Eyes Open condition (p=0.005).
No significant differences were identified between the Balance+ and Balance-
groups. CONCLUSIONS: At 1-month post-concussion, adolescents demonstrated balance
deficits compared to non-injured adolescents regardless of whether they reported
balance problems. These results suggest that self-reported balance status might
not be an accurate reflection of balance performance following a concussion in
adolescents.
PMID- 28495202
TI - Editor's Perspectives - May 2017.
PMID- 28495203
TI - Treatment of air leak in polytrauma patients with blunt chest injury.
AB - INTRODUCTION: Precise diagnostics and an adequate therapeutic approach are
mandatory in the treatment of air leak in polytrauma patients with blunt chest
trauma. The aim of this study was to evaluate the incidence, characteristics, and
management of air leak following this injury pattern. PATIENTS AND METHODS: Data
from 110 polytrauma patients was collected retrospectively. Fifty-four patients
received initial treatment by chest tube placement for pneumothorax. These
patients were classified into two groups, one with severe air leak and one with
minor air leak. An evaluation of injury pattern, chest wall injuries in
particular, duration of air leak, reason for drainage maintenance in place,
hospital length of stay, ICU stay, ventilator duration, type of treatment, and
the delay to surgical intervention was performed. RESULTS: Whereas 4 patients
showed severe air leak and were subsequently scheduled for timely surgical
intervention, the remaining 50 patients only showed minor air leak. Only 7
patients with minor air leak suffered from prolonged air leak (>5days), which
spontaneously resolved in all of them after a mean duration of 7.7days (range 6
12days). Absence of a prolonged air leak resulted in a shorter length of stay and
a shorter duration of mechanical ventilation, although no statistical
significance was observed. CONCLUSIONS: Early spontaneous cessation of most minor
air leaks as well as early surgical intervention for severe air leak lead to very
satisfactory patient outcomes with a relatively short hospital stay in our
patients. We therefore advocate early surgery for lacerations of the pulmonary
parenchyma resulting in severe air leak, whereas minor air leaks can usually be
treated conservatively.
PMID- 28495204
TI - Intracranial pressure monitoring in severe traumatic brain injuries: a closer
look at level 1 trauma centers in the United States.
AB - INTRODUCTION: The Brain Trauma Foundation (BTF) recently updated recommendations
for intracranial pressure (ICP) monitoring in severe traumatic brain injury
(TBI). The effect of ICP monitoring on outcomes is controversial, and compliance
with BTF guidelines is variable. The purpose of this study was to assess both
compliance and outcomes at level I trauma centers. MATERIALS AND METHODS: The
American College of Surgeons Trauma Quality Improvement Program database was
queried for all patients admitted to level I trauma centers with isolated blunt
severe TBI (AIS>3, GCS<9) who met criteria for ICP monitoring. Patients who had
severe extracranial injuries, craniectomy, or death in the first 24h were
excluded. Comparison between groups with and without ICP monitoring was made,
analyzing demographics, comorbidities, mechanism of injury, head Abbreviated
Injury Scale (AIS), vital signs on admission, head CT scan findings. Outcomes
included in-hospital mortality, mechanical ventilation days, intensive care unit
(ICU) length of stay, hospital length of stay, systemic complications, and
functional independence at discharge. Multivariable analysis was used to identify
independent risk factors for each of the outcomes. RESULTS: Overall, 4880
patients were included. ICP monitoring was used in 529 patients (10.8%). Stepwise
logistic regression analysis identified ICP monitor placement as an independent
risk factor for mortality (OR 1.63; 95% CI 1.28-2.07; p<0.001), mechanical
ventilation (OR 5.74 95% CI 4.42-7.46; p<0.001), ICU length of stay (OR 4.03; 95%
CI 2.94-5.52; p<0.001), systemic complications (OR 2.78; 95% CI 2.29-3.37;
p<0.001), and decreased functional independence at discharge (OR 1.71 95% CI 1.29
2.26; p<0.001). Subgroup analysis of patients with head AIS 3, 4, and 5 confirmed
that ICP monitors remained an independent risk factor for mortality in both head
AIS 4 and 5. CONCLUSIONS: Compliance with BTF guidelines for ICP monitoring is
low, even at level I trauma centers. In this study, ICP monitoring was associated
with poor outcomes, and was found to be an independent risk factor for mortality.
Further studies are needed to determine the optimal role of ICP monitoring in the
management of severe TBI.
PMID- 28495205
TI - Gatekeeping and the utilization of physician services in France: Evidence on the
Medecin traitant reform.
AB - In 2005, France implemented a gatekeeping reform designed to improve care
coordination and to reduce utilization of specialists' services. Under this
policy, patients designate a medecin traitant, typically a general practitioner,
who will be their first point of contact during an episode of care and who will
provide referrals to specialists. A key element of the policy is that patients
who self-refer to a specialist face higher cost sharing than if they received a
referral from their medecin traitant. We consider the effect of this policy on
the utilization of physician services. Our analysis of administrative claims data
spanning the years 2000-2008 indicates that visits to specialists, which were
increasing in the years prior to the implementation of the reform, fell after the
policy was in place. Additional evidence from the administrative claims as well
as survey data suggest that this decline arose from a reduction in self
referrals, which is consistent with the objectives of the policy. Visits fell
significantly both for specialties targeted by the policy and specialties for
which self-referrals are still allowed for certain treatments. This apparent
spillover effect may suggest that, at least initially, patients did not
understand the subtleties of the policy.
PMID- 28495206
TI - Universal block diagram based modeling and simulation schemes for fractional
order control systems.
AB - Universal block diagram based schemes are proposed for modeling and simulating
the fractional-order control systems in this paper. A fractional operator block
in Simulink is designed to evaluate the fractional-order derivative and integral.
Based on the block, the fractional-order control systems with zero initial
conditions can be modeled conveniently. For modeling the system with nonzero
initial conditions, the auxiliary signal is constructed in the compensation
scheme. Since the compensation scheme is very complicated, therefore the
integrator chain scheme is further proposed to simplify the modeling procedures.
The accuracy and effectiveness of the schemes are assessed in the examples, the
computation results testify the block diagram scheme is efficient for all Caputo
fractional-order ordinary differential equations (FODEs) of any complexity,
including the implicit Caputo FODEs.
PMID- 28495207
TI - Targeting the Hsp90 C-terminal domain to induce allosteric inhibition and
selective client downregulation.
AB - BACKGROUND: Inhibition of Hsp90 is desirable due to potential downregulation of
oncogenic clients. Early generation inhibitors bind to the N-terminal domain
(NTD) but C-terminal domain (CTD) inhibitors are a promising class because they
do not induce a heat shock response. Here we present a new structural class of
CTD binding molecules with a unique allosteric inhibition mechanism. METHODS: A
hit molecule, NSC145366, and structurally similar probes were assessed for
inhibition of Hsp90 activities. A ligand-binding model was proposed indicating a
novel Hsp90 CTD binding site. Client protein downregulation was also determined.
RESULTS: NSC145366 interacts with the Hsp90 CTD and has anti-proliferative
activity in tumor cell lines (GI50=0.2-1.9MUM). NSC145366 increases Hsp90
oligomerization resulting in allosteric inhibition of NTD ATPase activity
(IC50=119MUM) but does not compete with NTD or CTD-ATP binding. Treatment of
LNCaP prostate tumor cells resulted in selective client protein downregulation
including AR and BRCA1 but without a heat shock response. Analogs had similar
potencies in ATPase and chaperone activity assays and variable effects on
oligomerization. In silico modeling predicted a binding site at the CTD dimer
interface distinct from the nucleotide-binding site. CONCLUSIONS: A set of
symmetrical scaffold molecules with bisphenol A cores induced allosteric
inhibition of Hsp90. Experimental evidence and molecular modeling suggest that
the binding site is independent of the CTD-ATP site and consistent with unique
induction of allosteric effects. GENERAL SIGNIFICANCE: Allosteric inhibition of
Hsp90 via a mechanism used by the NSC145366-based probes is a promising avenue
for selective oncogenic client downregulation.
PMID- 28495209
TI - Young children consider individual authority and collective agreement when
deciding who can change rules.
AB - Young children demonstrate awareness of normativity in various domains of social
learning. It is unclear, however, whether children recognize that rules can be
changed in certain contexts and by certain people or groups. Across three
studies, we provided empirical evidence that children consider individual
authority and collective agreement when reasoning about who can change rules. In
Study 1, children aged 4-7years watched videos of children playing simply sorting
and stacking games in groups or alone. Across conditions, the group game was
initiated (a) by one child, (b) by collaborative agreement, or (c) by an adult
authority figure. In the group games with a rule initiated by one child, children
attributed ability to change rules only to that individual and not his or her
friends, and they mentioned ownership and authority in their explanations. When
the rule was initiated collaboratively, older children said that no individual
could change the rule, whereas younger children said that either individual could
do so. When an adult initiated the rule, children stated that only the adult
could change it. In contrast, children always endorsed a child's decision to
change his or her own solitary rule and never endorsed any child's ability to
change moral and conventional rules in daily life. Age differences corresponded
to beliefs about friendship and agreement in peer play (Study 2) and disappeared
when the decision process behind and normative force of collaboratively initiated
rules were clarified (Study 3). These results show important connections between
normativity and considerations of authority and collaboration during early
childhood.
PMID- 28495208
TI - Presence of Viral microRNA in Extracellular Environments.
PMID- 28495210
TI - 3 Tesla 23Na Magnetic Resonance Imaging During Acute Kidney Injury.
AB - RATIONALE AND OBJECTIVES: Sodium and proton magnetic resonance imaging (23Na/1H
MRI) have shown that muscle and skin can store Na+ without water. In chronic
renal failure and in heart failure, Na+ mobilization occurs, but is variable
depending on age, dialysis vintage, and other features. Na+ storage depots have
not been studied in patients with acute kidney injury (AKI). MATERIALS AND
METHODS: We studied 7 patients with AKI (mean age: 51.7 years; range: 25-84) and
14 age-matched and gender-matched healthy controls. All underwent 23Na/1H-MRI at
the calf. Patients were studied before and after acute hemodialysis therapy
within 5-6 days. The 23Na-MRI produced grayscale images containing Na+ phantoms,
which served to quantify Na+ contents. A fat-suppressed inversion recovery
sequence was used to quantify H2O content. RESULTS: Plasma Na+ levels did not
change. Mean Na+ contents in muscle and skin did not significantly change
following four to five cycles of hemodialysis treatment (before therapy: 32.7 +/-
6.9 and 44.2 +/- 13.5 mmol/L, respectively; after dialysis: 31.7 +/- 10.2 and
42.8 +/- 11.8 mmol/L, respectively; P > .05). Water content measurements did not
differ significantly before and after hemodialysis in muscle and skin (P > .05).
Na+ contents in calf muscle and skin of patients before hemodialysis were
significantly higher than in healthy subjects (16.6 +/- 2.1 and 17.9 +/- 3.2) and
remained significantly elevated after hemodialysis. CONCLUSIONS: Na+ in muscle
and skin accumulates in patients with AKI and, in contrast to patients receiving
chronic hemodialysis and those with acute heart failure, is not mobilized with
hemodialysis within 5-6 days.
PMID- 28495211
TI - Maximum Aortic Valve Opening Phase for Annulus Sizing in Pre-TAVR CTA.
AB - RATIONALE AND OBJECTIVES: The optimal phase for the measurement of the aortic
annular area for transcatheter aortic valve replacement (TAVR) is not
standardized, although most agree that systolic measurements are preferred, when
the annulus is larger. We hypothesized that the maximum annular area occurs at
the cardiac phase of the maximum aortic valve opening (MAVO) and that this phase
can be accurately and reproducibly assessed by visual inspection only. MATERIALS
AND METHODS: The aortic valve opening area was inspected visually by two readers
to determine the MAVO phase. The annular area was measured at the MAVO phase and
the typical systolic phase (35% of the R-R interval). Differences in the annular
area that would change valve sizing for prostheses were noted. RESULTS: Fifty
patients (mean age 81) were studied. Ninety percent had the MAVO at the 15%-25% R
R interval. There was high interobserver correlation (0.89) for determining the
MAVO phase by visual inspection. For 49 out of 50 patients, the annular area was
maximal at the MAVO phase. The mean difference in the annular area between the
MAVO phase and 35% was 22.3 (+/-4.57) mm2. In 12% of the patients, the difference
in the annular area changed the recommended size of a self-expanding prosthesis
and would have altered the procedure in 32% for balloon-expandable prostheses.
CONCLUSIONS: Visually assessed MAVO occurs in early systole for most patients and
is almost always the cardiac phase of the maximal aortic annular area. This
method allows rapid and reproducible determination of the appropriate phase for
TAVR planning measurements. Consideration should be given to optimizing pre-TAVR
computed tomography acquisitions for early systolic reconstruction and visual
determination of the MAVO.
PMID- 28495212
TI - Quantification of Mouse Renal Perfusion Using Arterial Spin Labeled MRI at 1 T.
AB - RATIONALE AND OBJECTIVES: Quantitative measurement of renal perfusion in murine
models provides important information on the organ physiology and disease states.
The 1-T desktop magnetic resonance imaging has a small footprint and a self
contained fringe field. This resultant flexibility in siting makes the system
ideal for preclinical imaging research. Our objective was to evaluate the
capability of the 1-T desktop magnetic resonance imaging to measure mouse renal
perfusion without the administration of exogenous contrast agents. MATERIALS AND
METHODS: We implemented a flow-sensitive alternating inversion recovery (FAIR)
based arterial spin labeling sequence with a mouse volume coil on a 1-T desktop
magnetic resonance scanner. The validity of the implementation was tested by
comparing obtained renal perfusion results with literature values for normal mice
and challenging the technique with mice treated with furosemide, a blood vessel
vasoconstrictor drug. RESULTS: The measured cortical and medullary perfusions
were quantified to be 402 +/- 95 and 184 +/- 52 mL/100 g/min, respectively, in
agreement with literature values. The ratio of cortical to medullary renal blood
flow was between 2 and 3 and was independent of the mouse weight. As expected,
upon furosemide injection, a decrease (~50%) in cortical perfusion was observed
in the mice population, at 1 hour post injection compared to baseline (P <
0.0001), which returned to baseline after 24 hours (P = 0.68). CONCLUSIONS: We
reported the successful application of FAIR-based arterial spin labeling for
noncontrast perfusion measurement of mouse kidneys using a 1-T desktop scanner.
The easy implementation of FAIR sequence on a 1-T desktop scanner offers the
potential for longitudinal perfusion studies in limited access areas such as
behind the barrier in mouse facilities and in multimodality preclinical imaging
laboratories without the administration of exogenous contrast agents.
PMID- 28495213
TI - Breast Density Legislation in New England: A Survey Study of Practicing
Radiologists.
AB - RATIONALE AND OBJECTIVES: This study aimed to assess radiologists' knowledge
about breast density legislation as well as perceived practice changes resulting
from the enactment of breast density legislation. MATERIALS AND METHODS: This is
an institutional review board-exempt anonymous email survey of 523 members of the
New England Roentgen Ray Society. In addition to radiologist demographics, survey
questions addressed radiologist knowledge of breast density legislation,
knowledge of breast density as a risk factor for breast cancer, recommendations
for supplemental screening, and perceived practice changes resulting from density
notification legislation. RESULTS: Of the 523 members, 96 responded, yielding an
18% response rate. Seventy-three percent of respondents practiced in a state with
breast density legislation. Sixty-nine percent felt that breast density
notification increased patient anxiety about breast cancer, but also increased
patient (74%) and provider (66%) understanding of the effect of breast density on
mammographic sensitivity. Radiologist knowledge of the relative risk of breast
cancer when comparing breasts of different density was variable. CONCLUSIONS:
Considerable confusion and controversy regarding breast density persists, even
among practicing radiologists.
PMID- 28495214
TI - Lesson Learned with the Use of Iliac Branch Devices: Single Centre 10 Year
Experience in 157 Consecutive Procedures.
AB - OBJECTIVE/BACKGROUND: Absence of an adequate iliac seal rarely represents an
absolute contraindication to endovascular abdominal aortic aneurysm repair. Iliac
branch devices (IBD) are increasingly used in patients with extensive aorto-iliac
aneurysmal disease, but few data are available on the long-term results of these
procedures. METHODS: Between 2006 and 2016, 157 consecutive IBD procedures
performed at a single centre were entered into a prospective database.
Indications included unilateral or bilateral common iliac artery aneurysms
combined or not with abdominal aortic aneurysms. Long-term results were reported
according to the Kaplan-Meier method. RESULTS: During the study period 149
patients were treated with an iliac branched endograft. Isolated IBD was
implanted in 17.8% of the cases; technical success rate was 97.5%. Peri-operative
procedure failure occurred in seven patients, four during surgery and three
within 30 days of the procedure. Presence of ipsilateral hypogastric aneurysm (p
= .031; Exp [B] = 6.72) and intervention performed during the initial study
period (p = .006; Exp [B] = 10.40) were predictive of early failure on
multivariate analysis. After a mean follow-up of 44.2 months actuarial freedom
from IBD related re-intervention was 97.4%, 95.6%, 94.0%, and 91.8% at 1, 3, 5,
and 9 years, respectively. Hypogastric artery patency was 94.7%, 92.6%, and 90.4%
at 1, 3, and 10 years, respectively. Presence of a hypogastric aneurysm was an
independent predictor of target artery occlusion during follow-up on multivariate
analysis (p = .007; Exp [B] = 5.93). CONCLUSION: Iliac branched endografting can
now be performed with a high technical success rate; long-term freedom from re
intervention is comparable with patients treated with standard aortic
endografting. IBD should be considered a first-option treatment in patients with
adequate vascular anatomy unsuitable for standard endovascular aortic repair.
PMID- 28495215
TI - Vertebral Penetration of an Inferior Vena Cava Filter.
PMID- 28495216
TI - What it should mean for an algorithm to pass a statistical Turing test for
detection of epileptiform discharges.
PMID- 28495217
TI - Individuals with mild MS with poor sleep quality have impaired visuospatial
memory and lower perceived functional abilities.
AB - BACKGROUND: Sleep disturbances are common in individuals with Multiple Sclerosis
(MS), but the impact of poor sleep quality on cognitive and physical function in
individuals with MS is less clear. OBJECTIVE/HYPOTHESIS: The purpose of this
study was to examine the relationship between sleep quality and cognitive and
physical function in individuals with mild MS. METHODS: Forty individuals with
relapsing-remitting or secondary-progressive MS (50.3 +/- 11.6 years of age)
participated. The Pittsburgh Sleep Quality Index (PSQI) was used to index sleep
quality. A PSQI of <=5 was considered good sleep quality and >5 was considered
poor sleep quality. Cognitive function was assessed using a battery of cognitive
tests, and physical function was assessed using 2 objective measures and a self
report measure. RESULTS: Thirteen individuals (32.5%) indicated good sleep
quality and 27 (67.5%) of the participants reported poor sleep quality. Those
with good sleep quality performed significantly better on a visuospatial memory
test (p = 0.025) and reported higher functional abilities (p < 0.001) compared to
those with poor sleep quality. There was no difference in performance on the
cognitive tests of verbal memory, information processing, or executive function,
or the objective function measures. Individuals with poor sleep quality had
higher levels of fatigue, depression, and anxiety, and lower quality of life.
CONCLUSIONS: Visuospatial memory appears to be the memory domain particularly
associated with poor sleep quality in people with mild MS. Also, individuals with
mild MS with poor sleep quality may underestimate their functional abilities.
PMID- 28495218
TI - Effects of hippocampal low-frequency stimulation in idiopathic non-human primate
epilepsy assessed via a remote-sensing-enabled neurostimulator.
AB - Individuals with pharmacoresistant epilepsy remain a large and under-treated
patient population. Continued technologic advancements in implantable
neurostimulators have spurred considerable research efforts directed towards the
development of novel antiepileptic stimulation therapies. However, the lack of
adequate preclinical experimental platforms has precluded a detailed
understanding of the differential effects of stimulation parameters on neuronal
activity within seizure networks. In order to chronically monitor seizures and
the effects of stimulation in a freely-behaving non-human primate with idiopathic
epilepsy, we employed a novel simultaneous video-intracranial EEG recording
platform using a state-of-the-art sensing-enabled, rechargeable clinical
neurostimulator with real-time seizure detection and wireless data streaming
capabilities. Using this platform, we were able to characterize the
electrographic and semiologic features of the focal-onset, secondarily
generalizing tonic-clonic seizures stably expressed in this animal. A series of
acute experiments exploring low-frequency (2Hz) hippocampal stimulation
identified a pulse width (150MUs) and current amplitude (4mA) combination which
maximally suppressed local hippocampal activity. These optimized stimulation
parameters were then delivered to the seizure onset-side hippocampus in a series
of chronic experiments. This long-term testing revealed that the suppressive
effects of low-frequency hippocampal stimulation 1) diminish when delivered
continuously but are maintained when stimulation is cycled on and off, 2) are
dependent on circadian rhythms, and 3) do not necessarily confer seizure
protective effects.
PMID- 28495219
TI - Increases in Use and Activity Due to Urban Renewal: Effect of a Natural
Experiment.
AB - INTRODUCTION: Urban green space and other recreational facilities are associated
with physical activity. For adolescents living in multistory housing, public
outdoor spaces that support physical activity may play an important role in
activity promotion strategies. However, stronger evidence for a relation between
the built environment and adolescent physical activity is scarce. DESIGN: A
natural experiment with a pre-experimental design was used with data collected in
2010 and 2012 before and after an urban renewal. Data were analyzed in 2016.
SETTING/PARTICIPANTS: Adolescents aged 11-16 years spending a minimum of 10
minutes daily within a 400-m buffer of the renewal district were included in the
analyses, resulting in 354 adolescents at baseline and 319 post-renewal.
INTERVENTION: A multicomponent urban renewal project of approximately 35 million
Euros in a disadvantaged neighborhood in the capital of Denmark occurred between
2010 and 2012. MAIN OUTCOME MEASURES: The main outcomes were changes in time
spent and physical activity within the area among adolescents, measured by
accelerometry (ActiGraph GT3X) and GPS devices (Qstarz BT-Q1000XT). RESULTS: Time
spent in the area was greater in 2012 than 2010 with an additional 24.6 minutes
per day (p=0.017). Of this time, 7.8 minutes were spent in light and 4.5 minutes
in moderate to vigorous physical activity. CONCLUSIONS: The present study
indicates that a multicomponent urban renewal strategy in a disadvantaged
district has the potential to increase time spent and physical activity in the
district for adolescents living in or close to the district.
PMID- 28495220
TI - Other Tobacco Product Use Among Sexual Minority Young Adult Bar Patrons.
AB - INTRODUCTION: Lesbian, gay, and bisexual (LGB) individuals smoke at rates 1.5-2
times higher than the general population, but less is known about LGB consumption
of other tobacco products (OTPs) and gender differences. OTP use among young
adult LGB bar patrons and the relationship among past quit attempts, intention to
quit, and binge drinking with OTP use was examined. METHODS: A cross-sectional
survey of young adults (aged 18-26) in bars/nightclubs in seven U.S. cities
between 2012 and 2014 (N=8,010; 1,101 LGB participants) was analyzed in 2016.
Logistic regressions examined current use of five OTPs (cigarillos, electronic
cigarettes, hookah, chewing tobacco, and snus) and sexual minority status,
adjusting for demographics and comparing LB women and GB men with their
heterosexual counterparts. RESULTS: LGB bar/nightclub patrons used all OTPs more
than their heterosexual counterparts. LB women were more likely than heterosexual
women to use cigarillos, electronic cigarettes, hookah, chew, and snus. GB men
were more likely than heterosexual men to smoke cigarillos, electronic
cigarettes, hookah, and use chew and snus. Past-year quit attempt was associated
with increased odds of electronic cigarette use in men and women, and increased
odds of dual use (cigarettes and OTPs) among men. Intention to quit was
negatively associated with dual use among women. Binge drinking was associated
with increased use of all OTPs across genders. CONCLUSIONS: LGB bar-going young
adults are at higher risk for OTP use than their heterosexual counterparts. Bar
based interventions are needed to address all forms of tobacco use in this high
risk group.
PMID- 28495221
TI - Impact of Provider Recommendation on Tdap Vaccination of Adolescents Aged 13-17
Years.
AB - INTRODUCTION: Tetanus, diphtheria, and acellular pertussis (Tdap) vaccination has
been recommended for adolescents in the U.S. since 2006. Information on Tdap
vaccination by provider recommendation is limited. The purpose of this study is
to assess recent Tdap vaccination by provider recommendation status among
adolescents aged 13-17 years. METHODS: The 2013 National Immunization Survey-Teen
data (N=18,948) were analyzed in 2016 to assess national and state-specific Tdap
vaccination coverage disparities among adolescents by provider recommendation
status, and other demographic and access to care variables. Multivariable
logistic regression analysis and predictive marginal modeling evaluated
associations between Tdap vaccination and provider recommendation status and
other factors among adolescents aged 13-17 years. RESULTS: Overall, only 56.9% of
adolescents aged 13-17 years received a provider recommendation for Tdap.
Coverage was significantly higher among adolescents with a provider
recommendation (88.6%) compared with those without a provider recommendation
(80.5%) (p<0.05). Multivariable logistic regression showed that characteristics
independently associated with a higher likelihood of Tdap vaccination included
receiving a provider recommendation, Hispanic ethnicity, having two to three
physician contacts in the past 12 months, having one or two vaccination
providers, and receiving vaccinations from more than one type of facility
(p<0.05). CONCLUSIONS: Provider recommendations were significantly associated
with Tdap vaccination among adolescents aged 13-17 years. However, 43% of parents
of adolescents did not receive a provider recommendation. Evidence-based
strategies such as standing orders and provider reminders alone or health systems
interventions in combination should be taken to improve provider recommendation
and Tdap vaccination coverage.
PMID- 28495222
TI - Job Characteristics Associated With Self-Rated Fair or Poor Health Among U.S.
Workers.
AB - INTRODUCTION: Approximately 60% of the U.S. adult population is employed. Many
aspects of a person's job may influence health, but it is unclear which job
characteristics are most strongly associated with health at a population level.
The purpose of this study was to identify important associations between job
characteristics and workers' self-rated health in a nationally representative
survey of U.S. workers. METHODS: Data from the 2010 National Health Interview
Survey were used to calculate weighted prevalence rates for self-reported
fair/poor health for five categories of job characteristics: occupation;
pay/benefits (economic); work organization; chemical/environmental hazards; and
psychosocial factors. Backward elimination methods were used to build a
regression model for self-reported health with the significant job
characteristics, adjusting for sociodemographic variables and health behaviors.
Data were collected in 2010 and analyzed in 2012-2016. RESULTS: After adjusting
for covariates, workers were more likely to have fair/poor health if they were
employed in business operations occupations (e.g., buyers, human resources
workers, event planners, marketing specialists; adjusted prevalence ratio
[APR]=1.85, 95% CI=1.19, 2.88); had no paid sick leave (APR=1.35, 95% CI=1.11,
1.63); worried about becoming unemployed (APR=1.43, 95% CI=1.22, 1.69); had
difficulty combining work and family (APR=1.23, 95% CI=1.01, 1.49); or had been
bullied/threatened on the job (APR=1.82, 95% CI=1.44, 2.29). CONCLUSIONS:
Occupation, lack of paid sick leave, and multiple psychosocial factors were
associated with fair/poor health among U.S. workers at the population level in
2010. Public health professionals and employers should consider these factors
when developing interventions to improve worker health.
PMID- 28495223
TI - Feasibility of Text Message Influenza Vaccine Safety Monitoring During Pregnancy.
AB - INTRODUCTION: The feasibility and accuracy of text messaging to monitor events
after influenza vaccination throughout pregnancy and the neonatal period has not
been studied, but may be important for seasonal and pandemic influenza vaccines
and future maternal vaccines. METHODS: This prospective observational study was
conducted during 2013-2014 and analyzed in 2015-2016. Enrolled pregnant women
receiving inactivated influenza vaccination at a gestational age <20 weeks were
sent text messages intermittently through participant-reported pregnancy end to
request fever, health events, and neonatal outcomes. Text message response rates,
Day 0-2 fever (>=100.4 degrees F), health events, and birth/neonatal outcomes
were assessed. RESULTS: Most (80.2%, n=166) eligible women enrolled. Median
gestational age was 8.9 (SD=3.9) weeks at vaccination. Response rates remained
high (80.0%-95.2%). Only one Day 0-2 fever was reported. Women reported via text
both pregnancy- and non-pregnancy-specific health events, not all associated with
medical visits. Most pregnancy-specific events in the electronic medical record
(EMR) were reported via text message. Of all enrollees, 84.9% completed the study
(131 reported live birth, ten reported pregnancy loss). Two losses reported via
text were not medically attended; there was one additional EMR-identified loss.
Gestational age and weight at birth were similar between text message-reported
and EMR-abstracted data and 95% CIs were overlapping for proportions of
prematurity, low birth weight, small for gestational age, and major birth
defects, as identified by text message-reported versus EMR-abstracted plus text
message-reported versus EMR-abstracted data only. CONCLUSIONS: This study
demonstrated the feasibility of text messaging for influenza vaccine safety
surveillance sustained throughout pregnancy. In these women receiving inactivated
influenza vaccination during pregnancy, post-vaccination fever was infrequent and
a typical pattern of maternal and neonatal health outcomes was observed.
PMID- 28495224
TI - A solid swing and ... contact [or miss]? Commentary on "Towards a Grand Unified
Theory of sports performance".
PMID- 28495225
TI - Detection and molecular status of Isospora sp. from the domestic pigeon (Columba
livia domestica).
AB - The domestic pigeon, Columba livia domestica, is reared for meat production, as a
pet, or for racing. Few reports have characterized the parasitic protists from
the genus Isospora isolated from Columbiformes. We detected Isospora-like oocysts
from C. livia reared for racing. The oocyst contained two sporocysts, and each
sporocyst included four sporozoites. The sporulated oocysts (n=4) were spherical;
their mean diameters were 25.6 (24.0-27.2)*24.7 (23.4-26.0) MUm. Micropyles,
polar granules, and oocyst residuum were absent. The mean length and width of the
sporocysts (n=8) were 19.5 (18.5-20.5) and 11.2 (10.2-12.1) MUm, respectively.
Stieda and sub-Stieda bodies were observed. Single-oocyst PCR revealed two
different 18S rRNA gene sequences and one 28S rRNA gene sequence in a single
oocyst of Isospora sp. Based on a phylogenetic analysis of the 18S rRNA gene, the
two sequences made a group which fell within a cluster of known avian Isospora
species. A tree based on the 28S rRNA gene sequence indicated that sequences from
the pigeon Isospora sp. fell within a cluster of avian Isospora species. Both
trees failed to clarify the phylogenetic relationships among the avian Isospora
species due to limited resolution. Because the morphological description of
Isospora sp. is based on only four oocysts, Isospora sp. is not proposed as a
novel species here. This is the first description of Isospora sp. isolated from
the domestic pigeon C. livia.
PMID- 28495226
TI - A gas flow model for layered landfills with vertical extraction wells.
AB - This paper developed a two-dimensional axisymmetric analytical model for layered
landfills with vertical wells. The model uses a horizontal layered structure to
describe the waste non-homogeneity with depth in gas generation, permeability and
temperature. The governing equations in the cylindrical coordinate system were
transformed to dimensionless forms and solved using a method of eigenfunction
expansion. After verification, the effects of different well boundary conditions
and gas extraction systems on recovery efficiency were investigated. A
dimensionless double-layer system, consisting of a cover and a waste layer, was
also explored. The results show that a constant vacuum pressure boundary
condition can be enough to describe a perforated pipe surrounded by drainage
gravel with a reasonable value of well radius, such as half the radius of gravel
fill. Also, the 7 independent variables (one marked with an asterisk is
dimensionless) of a double-layer system can be integrated into 3 dimensionless
ones: Cover permeability Kv1*/(Vertical gas permeability of waste Kv2**Cover
thickness h1*),-Vacuum pressure pw*PatmKv2*/(MURgT2*Gas generation rate of waste
s2) and ln(Well radius rw*)/(Anisotropy degree of waste k2*). The integration is
based on the inherent mechanism of this flow system with certain simplification.
The effects of these variables are then quantitatively characterized for a better
understanding of gas recovery efficiency. Same recovery efficiency can be
achieved with different variable combinations. For example, increasing h1* (such
as doubling it) has the same effect with decreasing Kv1* (such as halving it).
Along with the reduction of variables by half, the integration can facilitate the
preliminary design, and is a small but important advance in the consideration of
MSW non-homogeneity.
PMID- 28495227
TI - Lab-scale co-digestion of kitchen waste and brown water for a preliminary
performance evaluation of a decentralized waste and wastewater management.
AB - An overall interaction is manifested between wastewater and solid waste
management schemes. At the Laboratory of Environmental Engineering (LISA) of the
University of Padova, Italy, the scientific and technical implications of putting
into practice a decentralized waste and wastewater treatment based on the
separation of grey water, brown water (BW - faecal matter) and yellow water (YW -
urine) are currently undergoing investigation in the Aquanova Project. An
additional aim of this concept is the source segregation of kitchen waste (KW)
for subsequent anaerobic co-digestion with BW. To determine an optimal mixing
ratio and temperature for use in the treatment of KW, BW, and eventually YW, by
means of anaerobic digestion, a series of lab-scale batch tests were performed.
Organic mixtures of KW and BW performed much better (max. 520mlCH4/gVS) in terms
of methane yields than the individual substrates alone (max. 220mlCH4/gVS). A
small concentration of urine proved to have a positive effect on anaerobic
digestion performance, possibly due to the presence of micronutrients in YW. When
considering high YW concentrations in the anaerobically digested mixtures, no
ammonia inhibition was observed until a 30% and 10% YW content was added under
mesophilic and thermophilic conditions, respectively.
PMID- 28495228
TI - Post-operative spondylodiscitis due to Propionibacterium acnes: A case report.
AB - Post-operative spondylodiscitis due to Propionibacterium acnes is rare, with only
a few cases reported in the literature. In this article, we report the case of a
76-year-old patient who suffered from spondylodiscitis T12-L1 discovered after 1
month of pain and fever. Antibiotic treatment was administered for 6 weeks
without revision surgery. Diagnosis remains incomplete, and preventive therapy
against this infection is not well known. There is no link between
immunosuppression and this infection. A cure has been reported in 98% of cases,
but further investigation is still required for the establishment of treatment
guidelines.
PMID- 28495229
TI - Intramedullary epidermoid cysts in adults: Case report and updated literature
review.
AB - Epidermoid cysts are classical tumors in neurosurgery, but spinal locations are
rare and intramedullary locations represent only approximately 80 cases in the
literature. Intramedullary epidermoid cysts arise from ectodermic tissue
inclusion during neural tube closure. Intramedullary epidermoid cysts are more
frequent in young patients and in a thoracic location. We report the case of a 61
year-old patient consulting for bilateral asymmetrical progressive paraparesis
and proprioceptive ataxia revealing a T3-T4 exophytic medullar epidermoid cyst.
The tumor was surgically removed with a favorable outcome. The capsule was
partially removed. The authors present an updated literature review of
intramedullary epidermoid cyst diagnosis, management and recommendations.
PMID- 28495230
TI - Electrocardiogram voltage discordance: Interpretation of low QRS voltage only in
the precordial leads.
AB - OBJECTIVES: To define clinical correlates of low voltage isolated to precordial
leads on the surface electrocardiogram (ECG). INTRODUCTION: Low voltage (V) on
the ECG is defined as QRS V<5mm in all limb leads and <10mm in all precordial
leads. The diagnostic use of ECGs with low voltage isolated to the precordial
leads with normal limb lead voltages is unclear. METHODS: Twelve-lead ECGs with
QRS V>5mm in one or more limb leads and <10mm in all precordial leads were
collected. Associated clinical conditions were determined from clinical data,
echocardiograms, and chest radiographs. RESULTS: Low precordial voltage was found
in 256 of 150,000 ECGs (~0.2%). 50.4% of patients had discordant ECGs that
correlated with classic etiologies, with a higher incidence of LV dilation in
those with classic etiologies than those without. CONCLUSION: Low precordial
voltage is associated with classic etiologies and LV dilation.
PMID- 28495231
TI - Descriptive study of the parkinsonian population in the north of France:
Epidemiological analysis and healthcare consumption.
AB - BACKGROUND: The "neurodegenerative diseases plan" under elaboration for the Hauts
de-France region requires better knowledge of the patient population and care
pathways. In France, the prevalence of Parkinson's disease (PD) has been
estimated from cohorts to be about 1-3 per 1000 inhabitants, but exhaustive data
are scarce for the general population. The purpose of this study was to evaluate
the prevalence of PD in the Hauts-de-France region and to assess PD-related
healthcare consumption. METHOD: A descriptive study was conducted to identify the
parkinsonian population in the Hauts-de-France region (including the
administrative districts of Pas-de-Calais and Picardie) for the year 2014.
Parkinsonian patients were identified from health insurance fund reimbursement
data using the following criteria: (i) reimbursement for a PD-specific
medication; (ii) attribution of long-duration disease status coded as PD; (iii)
hospital stay with PD diagnosis in the standard discharge report contained in the
French medico-economic database on hospital activity (PMSI). RESULTS: The raw
prevalence of PD in the region was 5.03 per 1000 inhabitants aged 20 years and
older. The standardized prevalence by health territory ranged from 4.0 to 9.0 per
1000 inhabitants aged 20 years and older. During the 1-year study period, 33.5%
of patients had a neurology consultation, 57.1% attended a physiotherapy session,
and 7.7% received speech therapy. Most of patients (79.6%) were treated with
levodopa, sometimes in combination with a catechol-O-methyl transferase inhibitor
(14.4%). Dopaminergic agonists were prescribed in 33.5% of cases. A neuroleptic
was prescribed for 6.9% of the population (clozapine for 25.9%). CONCLUSION: The
prevalence of PD is high in the Hauts-de-France region with a heterogeneous
distribution by health territory. Neurology consultations were attended by a
minority of patients in 2014. This work provides perspectives for necessary
improvement in specialized care for this disease, both in terms of follow-up
consultations and home care.
PMID- 28495232
TI - Management and outcome of cerebral venous thrombosis after head trauma: A case
series.
AB - Cerebral venous thrombosis (CVT) is an underdiagnosed complication of head
trauma. To date, initiation of anticoagulation is still a matter of debate
because of the risk of worsening traumatic hemorrhage. This report describes a
case series of five patients admitted for head injury complicated by CVT. The
main associated radiological signs were skull fractures crossing the venous sinus
and adjacent traumatic hematoma. In four patients, anticoagulation was introduced
within 48-72h of CVT diagnosis, with no subsequent hemorrhagic complications. The
present report and data from the literature raise the question of systematic
additional venoscans when confronted by associated radiological features of post
traumatic CVT. The safety of anticoagulation in selected patients is also
discussed.
PMID- 28495233
TI - Sorption and speciation of iodine in groundwater system: The roles of organic
matter and organic-mineral complexes.
AB - Characterizing the properties of main host of iodine in soil/sediment and the
geochemical behaviors of iodine species are critical to understand the mechanisms
of iodine mobilization in groundwater systems. Four surface soil and six
subsurface sediment samples were collected from the iodine-affected area of
Datong basin in northern China to conduct batch experiments and to evaluate the
effects of NOM and/or organic-mineral complexes on iodide/iodate geochemical
behaviors. The results showed that both iodine contents and kf-iodate values had
positive correlations with solid TOC contents, implying the potential host of NOM
for iodine in soil/sediment samples. The results of chemical removal of easily
extracted NOM indicated that the NOM of surface soils is mainly composed of
surface embedded organic matter, while sediment NOM mainly occurs in the form of
organic-mineral complexes. After the removal of surface sorbed NOM, the decrease
in kf-iodate value of treated surface soils indicates that surface sorbed NOM
enhances iodate adsorption onto surface soil. By contrast, kf-iodate value
increases in several H2O2-treated sediment samples, which was considered to
result from exposed rod-like minerals rich in Fe/Al oxyhydroxide/oxides. After
chemical removal of organic-mineral complexes, the lowest kf-iodate value for
both treated surface soils and sediments suggests the dominant role of organic
mineral complexes on controlling the iodate geochemical behavior. In comparison
with iodate, iodide exhibited lower affinities on all (un)treated soil/sediment
samples. The understanding of different geochemical behaviors of iodine species
helps to explain the occurrence of high iodine groundwater with iodate and iodide
as the main species in shallow (oxidizing conditions) and deep (reducing
conditions) groundwater.
PMID- 28495234
TI - Oxidative stress-induced Akt downregulation mediates green tea toxicity towards
prostate cancer cells.
AB - Green tea consumption has been shown to possess cancer chemopreventive activity.
Polyphenol E (PE) is a widely used standardized green tea extract formulation.
This study was designed to investigate the impact of PE on prostate cancer cells
(PC3), analyze the potential signals involved and elucidate whether anti- or pro
oxidant effects may be implicated. Treatment of PC3 cells with 30 and 100MUg/ml
PE significantly decreased cell viability and proliferation. At the tested
concentrations, PE did not exert any antioxidant activity, eliciting instead a
pro-oxidant effect at concentrations 30 and 100MUg/ml, which was consistent with
the observed PE cytotoxicity. PE-induced cell death was associated with
mitochondrial dysfunction and downregulation of Akt activation, thus suggesting
their implication in the PE-elicited cell dysfunction. Cell exposure to the ROS
scavenger N-Acetyl Cysteine prevented PE-induced ROS increase, pAkt impairment,
and cell death, clearly indicating the causative role of ROS in the observed
phenomena. Failure of PE to induce PC3 damage in cells overexpressing Akt further
confirms its implication in the PE-elicited cell death. Our findings showed an
association between the antiproliferative and the pro-oxidant effect elicited by
PE on PC3 cells and delineates a molecular signaling pattern potentially
implicated in the toxicity of PE towards prostate cancer cells.
PMID- 28495235
TI - Prenatal detection of megacystis: not always an adverse prognostic factor.
Experience in 25 consecutive cases in a tertiary referral center, with complete
neonatal outcome and follow-up.
AB - INTRODUCTION: Megacystis is a condition of abnormal enlarged fetal bladder for
gestational age, which is usually associated with urological malformations that
may constitute a life-threatening condition for the baby. OBJECTIVE: The purpose
of this study was to assess the prognostic and etiological criteria of fetal
megacystis and to describe the neonatal outcome in a large series collected in a
single tertiary center. STUDY DESIGN: A retrospective observational study was
conducted between 2008 and 2012. We reviewed all consecutive cases of fetal
megacystis diagnosed during routine ultrasound (US) screening. The following data
were collected and analyzed: maternal age, gestational age at diagnosis, prenatal
ultrasonographic details of the urinary system, extra-urinary ultrasonographic
anomalies, fetal karyotype, pregnancy outcome, postnatal diagnosis, and
medical/surgical follow-up. RESULTS: Of the 25 fetuses included in this study,
76% were males. The mean gestational age (GA) at diagnosis was 23.1 +/- 7.5 weeks
(range 12-34), among them only four (16%) were diagnosed during the first
trimester. Associated urological malformations were detected in 92% (n = 23) of
the cases, while other malformations were detected in 36% (n = 9).
Oligohydramnios or anyhydramnios were observed in 52% (n = 13) of the cases.
Twelve (48%) fetuses were considered as having poor prognosis for renal function.
Vesicocentesis with or without vesico-amniotic infusion were performed in 28% (n
= 7) of the cases. Pregnancy outcome was surprisingly good, with only one case of
prenatal death and survival rate of 96% (n = 24) of liveborn babies. Posterior
urethral valve (PUV) (n = 9, 36%) was the most common etiology of the fetal
megacystis, followed by persistent urogenital sinus (n = 2, 8%), Prune belly
syndrome (n = 2, 8%) and bilateral vescico-ureteral reflux (VUR) (n = 2, 8%).
Surgical or endoscopic procedures were performed in 75% (n = 18) of the cases.
Six (24%) newborns presented with moderate/severe respiratory distress that
requested invasive assisted ventilation. Three cases (n = 3, 12%) of perinatal
death were observed due to severe impaired renal function. After a median follow
up of 29 months renal function was good in 79% (n = 19) of the cases.
CONCLUSIONS: Fetal megacystis may underline a wide range of associated
pathologies with the highest prevalence of urinary malformation. Optimal
counseling of the involved parents requires a multidisciplinary approach to allow
the best management during the pregnancy and the perinatal period. Despite the
high risk of renal failure, lung hypoplasia, and severe associated anomalies, the
outcome of fetuses with megacystis could be improved thanks to an appropriate
perinatal diagnosis and neonatal management.
PMID- 28495236
TI - Fireworks type, injury pattern, and permanent impairment following severe
fireworks-related injuries.
AB - BACKGROUND: There is a paucity of clinical data on severe fireworks-related
injuries, and the relationship between firework types, injury patterns, and
magnitude of impairment is not well understood. Our objective was to describe the
relationship between fireworks type, injury patterns, and impairment. METHODS:
Retrospective case series (2005-2015) of patients who sustained consumer
fireworks-related injuries requiring hospital admission and/or an operation at a
Level 1 Trauma/Burn Center. Fireworks types, injury patterns (body region, injury
type), operation, and permanent impairment were examined. RESULTS: Data from 294
patients 1 to 61years of age (mean 24years) were examined. The majority (90%)
were male. 119 (40%) patients were admitted who did not undergo surgery, 163
(55%) patients required both admission and surgery, and 12 (5%) patients
underwent outpatient surgery. The greatest proportion of injuries was related to
shells/mortars (39%). There were proportionally more rocket injuries in children
(44%), more homemade firework injuries in teens (34%), and more shell/mortar
injuries in adults (86%). Brain, face, and hand injuries were disproportionately
represented in the shells/mortars group. Seventy percent of globe-injured
patients experienced partial or complete permanent vision loss. Thirty-seven
percent of hand-injured patients required at least one partial or whole
finger/hand amputation. The greatest proportion of eye and hand injuries
resulting in permanent impairment was in the shells/mortars group, followed by
homemade fireworks. Two patients died. CONCLUSIONS: Severe fireworks-related
injuries from homemade fireworks and shells/mortars have specific injury
patterns. Shells/mortars disproportionately cause permanent impairment from eye
and hand injury.
PMID- 28495237
TI - Multigene panels in Ashkenazi Jewish patients yield high rates of actionable
mutations in multiple non-BRCA cancer-associated genes.
AB - OBJECTIVE: To evaluate the results of multigene panel testing among Ashkenazi
Jewish compared with non-Ashkenazi Jewish patients. METHODS: We reviewed the
medical records for all patients who underwent multigene panel testing and
targeted BRCA1/2 testing at a single institution between 6/2013-1/2015. Clinical
actionability for identified pathogenic mutations was characterized based on the
National Comprehensive Cancer Network (NCCN) guidelines and consensus statements
and expert opinion for genes not addressed by these guidelines. RESULTS: Four
hundred and fifty-four patients underwent multigene panel screening, including
138 Ashkenazi Jewish patients. The median patient age was fifty-two years. Three
hundred and fifty-four patients (78%) had a personal history of cancer. Two
hundred and fifty-one patients had breast cancer, 49, ovarian cancer, 26, uterine
cancer and 20, colorectal cancer. We identified 62 mutations in 56 patients and
291 variants of uncertain significance in 196 patients. Among the 56 patients
with mutations, 51 (91%) had actionable mutations. Twenty mutations were
identified by multigene panels among Ashkenazi Jewish patients, 18 of which were
in genes other than BRCA1/2. A review of targeted BRCA1/2 testing performed over
the same study period included 103 patients and identified six mutations in
BRCA1/2, all of which occurred in Ashkenazi Jewish patients. Among all Ashkenazi
Jewish patients undergoing genetic testing, 25/183 (14%) had a mutation, 24/25 of
which were actionable (96%) and 17/25 patients (68%) had mutations in non BRCA1/2
genes. CONCLUSIONS: With the rapid acceptance of multigene panels there is a
pressing need to understand how this testing will affect patient management.
While traditionally many Ashkenazi Jewish patients have undergone targeted
BRCA1/2 testing, our data suggest consideration of multigene panels in this
population as the majority of the results are clinically actionable and often in
genes other than BRCA1/2.
PMID- 28495238
TI - Uncovering the role of nuclear Lysyl oxidase (LOX) in advanced high grade serous
ovarian cancer.
AB - OBJECTIVE: Lysyl oxidase (LOX) is an enzyme that catalyzes the cross-linking of
collagen and elastin in the extracellular matrix, thus controlling the tensile
strength of tissues. Along with this primary function, there are evidences
supporting a role for LOX in many critical biological functions, including gene
expression regulation, cell growth, adhesion and migration. Accordingly, recent
studies have supported a pivotal role for LOX in cancer progression and
metastasis. The current study aimed at investigating the prognostic significance
and the functional role of intracellular LOX in ovarian cancer. METHODS: To this
end, we analyzed LOX expression by immunohistochemistry in archived tumor
material from advanced high grade serous ovarian cancer (HGSOC) patients (n=70)
and correlated data with clinicopathological parameters and with response to
chemotherapy. In vitro experiments were also used to investigate the functional
consequences of LOX expression on behavioral aspects of HGSOC cells. RESULTS: Our
results showed that nuclear LOX expression is associated with unfavorable outcome
in advanced HGSOC, being an independent prognostic factor for disease recurrence.
Besides, high nuclear levels were seen to be associated with resistance to first
line chemotherapy. Through gene expression modulation experiments in HGSOC cell
lines, we demonstrate that LOX positively regulates cell proliferation, migration
and anchorage-independent growth. CONCLUSIONS: Collectively, our data suggest
that LOX functions as a tumor promoter in HGSOC and positively regulates several
aspects of the metastatic cascade.
PMID- 28495239
TI - Prognostic value of miliary versus non-miliary sub-staging in advanced ovarian
cancer.
AB - OBJECTIVE: The presence of miliary disease during initial ovarian cancer
debulking may reflect a distinct mode of peritoneal spread independent from size
based tumor staging and may explain variation in response to treatment and
survival outcomes. To infer the prevalence, presentation and clinical
implications of miliary disease we reviewed existing surgical records. METHODS:
Reports were available for 1008 primary debulking surgeries for ovarian, primary
peritoneal or fallopian tube cancer between 2001 and 2015 (685 reports from 2005
to 2015). Clinical outcome data was available for 938 patients. We analyzed a
high-stage sub-cohort for survival (N=436). RESULTS: Most records were evaluable
for miliary disease (761/938); for these, the miliary phenotype was highly
prevalent (249/761, 32.7%) and often accompanied by ascites (185/249, 74%). While
optimal debulking rates were unaffected by miliary disease, total resection (R0)
rates were poorer. Liver, stomach, spleen or bladder appeared to be sporadically
involved while the omentum, mesentery, bowel, peritoneum and diaphragm were
affected simultaneously (Spearman rho>0.5). Overall, miliary disease was
associated with worse progression free survival, overall survival, and time from
relapse to death independent of stage. Survival effects were particularly strong
for Stage IV disease where median overall survival varied by over 30months (log
rank p=0.002). CONCLUSIONS: Miliary disease is an identifiable surgical phenotype
reflecting a distinct clinical trajectory that adds prognostic information to
standard disease burden-based staging. These findings should permit further
retrospective investigation in a wider cohort and prompt the consideration of
prospective structured operative reporting standards and treatment strategies.
PMID- 28495240
TI - Risk factors for pulmonary complication following fixation of spine fractures.
AB - BACKGROUND CONTEXT: Previous studies have suggested pulmonary complications are
common among patients undergoing fixation for traumatic spine fractures. This
leads to prolonged hospital stay, worse functional outcomes, and increased
economic burden. However, only limited prognostic information exists regarding
which patients are at greatest risk for pulmonary complications. PURPOSE: This
study aimed to identify factors predictive of perioperative pulmonary
complications in patients undergoing fixation of spine fractures. STUDY
DESIGN/SETTING: A retrospective review in a level 1 trauma center was carried
out. PATIENT SAMPLE: The patient sample comprised 302 patients with spinal
fractures who underwent operative fixation. OUTCOME MEASURES: The outcome
measures were postoperative pulmonary complications (physiological and functional
measures). MATERIALS AND METHODS: Demographic and injury features were recorded,
including age, gender, body mass index (BMI), American Society of
Anesthesiologists (ASA) classification, mechanism of injury, injury
characteristics, and neurologic status. Treatment details, including surgery
length, timing, and approach were reviewed. Postoperative pulmonary complications
were recorded after a minimum of 6 months' follow-up. RESULTS: Forty-seven
pulmonary complications occurred in 42 patients (14%), including pneumonia (35),
adult respiratory distress syndrome (ARDS) (10), and pulmonary embolism (2).
Logistic regression found spinal cord injury (SCI) to be most predictive of
pulmonary complications (odds ratio [OR]=4.4, 95% confidence interval [CI] 1.9
10.1), followed by severe chest injury (OR 2.7, 95% CI 1.1-6.9), male gender (OR
2.7, 95% CI 1.1-6.8), and ASA classification (OR 2.3, 95% CI 1.4-4.0). Pulmonary
complications were associated with significantly longer hospital stays (23.9 vs.
7.7 days, p<.01), stays in the intensive care unit (ICU) (19.9 vs. 3.4 days,
p<.01), and increased ventilator times (13.8 days vs. 1.9 days, p<.01).
CONCLUSIONS: Several factors predicted development of pulmonary complications
after operative spinal fracture, including SCI, severe chest injury, male gender,
and higher ASA classification. Practitioners should be especially vigilant for of
postoperative complications and associated injuries following upper-thoracic
spine fractures. Future study must focus on appropriate interventions necessary
for reducing complications in these high-risk patients.
PMID- 28495241
TI - The natural course of prevertebral soft tissue swelling after anterior cervical
spine surgery: how long will it last?
AB - BACKGROUND CONTEXT: Prevertebral soft tissue swelling (PSTS) after anterior
cervical spine surgery (ACSS) has been regarded as one of the critical
complications that cause airway obstruction. Still, however, no research has
dealt with how PSTS returns to presurgery status after ACSS; most recommendations
are being performed without information about its natural course, focusing on
acute-phase swelling after surgery. PURPOSE: The study aimed to examine how long
postsurgery PSTS lasts and when it returns to its presurgery state, and to
analyze the actual influence of a number of factors to observe the natural
progress of postsurgery PSTS. STUDY DESIGN/SETTING: This is a prospective
observational study. PATIENT SAMPLE: The sample included a total of 160 patients
who underwent ACSS, including anterior cervical discectomy and fusion (ACDF) and
cervical total disc replacement (TDR). OUTCOME MEASURES: The diameter of PSTS
measured at each set time point after surgeries was compared with PSTS
measurements before surgery, and analyzed with factors influencing PSTS. METHODS:
Anterior and posterior diameters of the anterior soft tissue of C3 (pharyngeal
airway) and C6 (laryngeal airway) were measured using simple lateral radiography
before surgery, immediately after surgery, at 2 weeks, 1, 3, 6, and 12 months
after surgery. The progress of postsurgery PSTS was analyzed according to
patients' individual characteristics, such as age, gender, weight, body mass
index (BMI), smoking status, use of antiplatelet therapy, hypertension and
diabetes mellitus, complaints of dysphagia, along with surgical factors such as
anesthesia time, operation time, numbers of involved operation segments,
transfusion, estimated blood loss , and operation method. Multivariable analysis
by generalized linear mixed model was used to perform additional univariable
analysis on variables found to be related to PSTS. In addition, to find the
postsurgery interval at which PSTS naturally stabilizes, repeated measures
analysis of variance and Bonferroni method were used to perform post-hoc tests.
There were no sources of funding and no conflicts of interest associated with
this study. RESULTS: For ACDF, the mean values (95% confidence interval [CI]) of
PSTS in C3 were 4.38 (4.04~4.71), 10.40 (9.64~11.17), 7.72 (7.10~8.35), 6.24
(5.74~6.69), 5.43 (5.03~5.82), 5.14 (4.77~5.50), and 4.96 (4.59~5.33) mm at each
follow-up time, respectively. In C6, the average values (95% CI) of PSTS were
14.43 (13.96~14.91), 19.18 (18.59~19.77), 17.92 (17.37~18.47), 16.98
(16.45~17.51), 16.18 (15.67~16.69), 15.95 (15.50~16.40), and 15.49 (15.50~16.40)
mm. For cervical TDR, the mean values (95% CI) of PSTS in C3 were 3.67
(3.45~3.89), 8.05 (7.17~8.93), 5.42 (4.92~5.91), 4.57 (4.21~4.92), 4.12
(3.99~4.36), 4.10 (3.87~4.34), and 3.90 (3.66~4.14) mm at each follow-up time,
respectively. In C6, the average values (95% CI) of PSTS were 13.61
(12.96~14.25), 16.51 (15.80~17.21), 15.77 (15.13~16.42), 15.24 (14.61~15.87),
14.62 (14.01~15.22), 14.52 (13.88~15.17), and 13.94 (13.20~14.68) mm. It is
discovered that PSTS after surgery returned to presurgery status within 1 to 3
months in the pharyngeal airway (C3) and within 3 to 6 months in the laryngeal
airway (C6), and gender, BMI, and surgery method (ACDF) were determined to be the
factors having influence on PSTS after surgery. CONCLUSIONS: It is necessary to
pay attention to PSTS and patient conditions after ACSS for at least 1 to 6
months postsurgery, depending on surgical method and operation levels.
PMID- 28495242
TI - The association between the Hospital Consumer Assessment of Healthcare Providers
and Systems (HCAHPS) survey and real-world clinical outcomes in lumbar spine
surgery.
AB - BACKGROUND CONTEXT: The patient experience of care as measured by the Hospital
Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey is
currently used to determine hospital reimbursement. The current literature
inconsistently demonstrates an association between patient satisfaction and
surgical outcomes. PURPOSE: To determine whether patient satisfaction with
hospital experience is associated with better clinical outcomes in lumbar spine
surgery. STUDY DESIGN: A retrospective cohort study conducted at a single
institution. PATIENT SAMPLE: A total of 249 patients who underwent lumbar spine
surgery between 2013 and 2015 and completed the HCAHPS survey. OUTCOME MEASURES:
Self-reported health status measures, including the EuroQol 5 Dimensions (EQ-5D),
Pain Disability Questionnaire (PDQ), and visual analog score for back pain (VAS
BP). METHODS: All patients undergoing lumbar spine surgery between 2013 and 2015
who completed an HCAHPS survey were studied. Patients were excluded from the
study if they had been diagnosed with spinal malignancy, scoliosis, or had less
than 1 year of follow-up. Patients who selected a 9 or 10 overall hospital rating
(OHR) on HCAHPS were placed in the satisfied group, and the remaining patients
comprised the unsatisfied group. The primary outcomes of this study include
patient-reported health status measures such as EQ-5D, PDQ, and VAS-BP. No funds
were received in support of this study, and the authors report no conflict of
interest-associated biases. RESULTS: Our study population consisted of 249
patients undergoing lumbar spine surgery. Of these, 197 (79%) patients selected
an OHR of 9 or 10 on the HCAHPS survey and were included in the satisfied group.
The only preoperative characteristics that differed significantly between the
twogroups were gender, a diagnosis of degenerative disc disease (DDD), heavy
preoperative narcotic use, and a diagnosis of chronic renal failure. At 1 year
follow-up, no statistically significant differences in EQ-5D, PDQ, or VAS-BP were
observed. After using multivariable linear regression models to assess the
association between patient satisfaction and pre- to 1-year postoperative changes
in health status measures, selecting a top-box OHR was not found to be
significantly associated with change in either EQ-5D (beta=0.055 [95% confidence
interval {CI}: -0.035 to 0.145]), PDQ (beta=-9.013 [95% CI: -23.782 to 5.755]),
or VAS-BP (beta=-0.849 [95% CI: -2.125 to 0.426]). These results suggest high
satisfaction with the hospital experience may not necessarily correlate with
favorable clinical outcomes. CONCLUSIONS: Top-box OHR was not associated with pre
to 1-year postoperative improvement in EQ-5D, PDQ, and VAS-BP. Although the
associations between high satisfaction and improvement in health status did not
reach statistical significance, the best estimates from our multivariable models
reflect greater clinical improvement with top-box satisfaction. Future studies
should seek to investigate whether HCAHPS are a reliable indicator of quality
care in lumbar spine surgery.
PMID- 28495243
TI - Validation of topographic hybrid single-photon emission computerized tomography
with computerized tomography scan in patients with and without nonspecific
chronic low back pain. A prospective comparative study.
AB - BACKGROUND CONTEXT: The evidence for the treatment for nonspecific chronic low
back pain (ns CLBP) is very weak. Besides the complexity of the pain experience,
a good biological marker or tool enabling identification of a pain generator is
lacking. Hybrid imaging, combining single-photon emission computerized tomography
(SPECT) with computerized tomography (CT) scan, has been proposed as useful in
the diagnostic workup of patients with CLBP. PURPOSE: To evaluate the sensitivity
of SPECT-CT in patients with ns CLBP (Group I) as compared with patients without
CLBP (Group II). STUDY DESIGN: A prospective comparative study. PATIENT SAMPLE:
Two hundred patients were enrolled: 96 in Group I and 104 in Group II. OUTCOME
MEASURES: Only the physiological measurement of the incidence of hot spots was
performed. The hot spots were rated as follows: 0=normal; 1=slightly colored (no
hot spot on whole-body bone scan); and 2=clear hot spot (can be identified on the
whole-body bone scan and confirmed on SPECT). To analyze the interobserver
agreement when using this scoring system, a second independent reading was
performed for 50 randomly chosen records. METHODS: Two hundred patients divided
into two groups were referred to the department of Medical and Molecular Imaging
for a topographic SPECT-CT. The first group consisted of patients with ns CLBP,
diagnosed by a neurosurgeon. The control group consisted of patients referred for
SPECT-CT for non-spinal conditions. Hot spots were assessed for all patients. A
second independent reading, blinded for the results of the first reader, was
performed on 25 randomly selected patients in each group. This study was
investigator initiated, and no funding was received. None of the authors or their
proxies have a potential conflict of interest. RESULTS: The odds of finding a
normal image in the control group are 2.05 times higher than in Group I. The
sensitivity score equals 2.37, meaning that the probability of detecting a hot
spot (levels 1 or 2) is more than two times higher in Group I. When focusing on
level 2 hot spots only, this score rises to 7.02, indicative of a high
sensitivity. CONCLUSIONS: Single-photon emission computerized tomography with
computerized tomography might have potential in the diagnostic workup of patients
with ns CLBP, owing to its higher sensitivity when compared with other advanced
medical imaging modalities.
PMID- 28495245
TI - Massive parallel sequencing identifies RAPSN and PDHA1 mutations causing fetal
akinesia deformation sequence.
AB - INTRODUCTION: Fetal akinesia deformation sequence (FADS) or arthrogryposis
multiplex congenita (AMC) is characterized by clinical ambiguity and genetic
heterogeneity, hampering genetic diagnosis via traditional sequencing methods.
Next generation sequencing (NGS) of all known disease-causing genes offers an
elegant solution to identify the genetic etiology of AMC/FADS in a diagnostic
setting. METHODS: An in-house developed disease-associated gene panel was
conducted in two unrelated fetuses with FADS. First, a de novo analysis was
performed on the entire disease-associated gene panel. If no pathogenic mutation
was identified, analysis of variants retained in a specific subpanel with
arthrogryposis/fetal akinesia-causing genes was performed. RESULTS: In the first
family, FADS relates to a homozygous c.484G > A (p.Glu162Lys) mutation in the
gene RAPSN. The second case concerns a sporadic patient with brain anomalies and
arthrogryposis due to a de novo hemizygous c.498C > T splice-site mutation in the
pyruvate dehydrogenase-alpha 1 (PDHA1) gene. DISCUSSION: NGS facilitated genetic
diagnosis, and hence genetic counseling, for both families with AMC/FADS.
Biallelic RAPSN mutations typically result in congenital myasthenia syndrome, or
occasionally in FADS. This is the first report attributing the RAPSN mutation
c.484G > A, identified in a homozygous state in patient 1, to FADS. The second
patient represents the first case of AMC due to a PDHA1 mutation, advocating that
pyruvate dehydrogenase deficiency should be considered in the differential
diagnosis of fetal akinesia. This study illustrates the relevance of a disease
associated-gene panel as a diagnostic tool in pregnancies complicated by this
genetically heterogeneous condition.
PMID- 28495244
TI - Rumen prokaryotic communities of ruminants under different feeding paradigms on
the Qinghai-Tibetan Plateau.
AB - Yak and Tibetan sheep are the major indigenous ruminants on the Qinghai-Tibetan
Plateau in China. The aim of this work was to study the differences in ruminal
fermentation parameters and rumen prokaryotic community composition between hosts
and feeding paradigms. The 16S rRNA genes targeting bacteria and archaea were
sequenced using the MiSeq platform. The results showed that the prokaryotic
community structure between yak and Tibetan sheep was significantly different
(P<0.01). A significant difference in structure was also found between groups of
yaks barn fed with a total mixed ration (TMR) and those naturally grazing (NG)
(P=0.034), as well as for Tibetan sheep of the two groups (P=0.026). The core
prokaryotic populations that existed in the rumen mostly dominated the structure.
There was an obvious correlation of the prokaryotic community composition at the
phylum and genus levels with the host or the feeding pattern. In addition,
Tibetan sheep showed significantly higher yields of volatile fatty acids (VFAs)
than yak, as did the NG group compared with the TMR group. In conclusion, both
the host and feeding pattern may influence rumen microbial ecology system, with
host effects being more important than those of the feeding pattern.
PMID- 28495246
TI - Clonidine adhesive patch for the treatment of tic disorders: A systematic review
and meta-analysis.
AB - OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of
clonidine adhesive patch for tic disorders (TDs). METHODS: Medline, Embase,
Cochrane central register of controlled trials and Chinese databases of CBM, CNKI
were searched from inception to 08.2016 for randomized controlled studies (RCTs),
open-label control studies of clonidine adhesive patch versus other medications
or/and placebo for TDs. The cochrane Handbook for Systematic Reviews of
Interventions was used to guide our study. RESULTS: Six studies involving 1145
participants were included in this study. Among these studies, two study (N = 513
patients) used placebo as a control and four studies (N = 632 patients) used
positive drug controls. The results of meta-analysis suggested that clonidine
adhesive patch may be as effective as haloperidol or tiapride for TDs. Adverse
events (AEs) were reported in all studies, and the most common AEs of clonidine
adhesive patch were rash (8.9%), lightheadedness (8.0%), dry mouth (4.0%). The
AEs of clonidine adhesive patch were slight. CONCLUSION: These data provide
moderate quality evidence that clonidine adhesive patch might be an effective and
safe treatment option for TDs, and results from further trials are urgently
needed to extend the evidence base.
PMID- 28495248
TI - Clinical benefits, echocardiographic and MRI assessment after pulmonary
sequestration treatment.
AB - BACKGROUND: This study aimed to explore systematically procedural results,
clinical benefits with echocardiographic and chest-MRI assessment of pulmonary
sequestration percutaneous treatment. METHODS: 13 consecutive infants and
children with diagnosis of isolated pulmonary sequestration (PS) had percutaneous
closure of the aberrant artery supplying pulmonary sequestration between 2010 and
2015. By protocol, echocardiographic and chest-MRI assessment was performed
before and respectively at 6-12months and 1year with the aim to study the effects
of embolization on heart volume overload and regression of pulmonary
sequestration. RESULTS: Median age at diagnosis was 1year (95%CI 0-2.6); median
age at treatment was 1.3years (95%CI1.01-2.85). In all pts the PS was confirmed
by chest-MRI. Procedural success was 100%. After treatment, pts experiencing
previously respiratory symptoms/infections remained asymptomatic at 2.9year
follow-up. In pts with significant shunt due to PS, treatment resulted in
amelioration in left or right cardiac chamber enlargement at 6 and 12month follow
up. At distance from PS closure (median 14months), chest-MRI confirmed the
closure of the aberrant artery and PS regression in 12 patients. In one case,
despite the acute procedural success and the supplying artery remained closed,
MRI detected residual PS revascularization. CONCLUSIONS: Percutaneous PS closure
in infants and children is safe and provide regression in respiratory symptoms
and heart chamber dilatation if significant shunt is present. MRI is able to
define aberrant artery course and PS parenchima, and might represent a valid
instrument to study residual PS parenchima during growth.
PMID- 28495247
TI - Hospital variation in treatment and outcomes in acute coronary syndromes:
Insights from the Alberta Contemporary Acute Coronary Syndrome Patients Invasive
Treatment Strategies (COAPT) study.
AB - BACKGROUND: We examined variation in hospital treatment and its relationship to
clinical outcome in a large population-based cohort of ACS patients within a
single payer-government funded health care system. METHODS: Patients hospitalized
in 106 hospitals in Alberta, Canada with a primary diagnosis of ACS were included
(July 1, 2010-March 31, 2013) with comparisons made across the three cardiac
catheterization-capable hospitals (Sites A-C). Cox proportional-hazard regression
models were used to examine the multivariable-adjusted association between site
and 1-year death or repeat cardiovascular (CV) hospitalization (primary
endpoint). RESULTS: Of 14,155 patients, 1938 (13.7%) were admitted to a community
hospital without transfer to an invasive hospital (10.7% in-hospital death). The
remaining were admitted (n=4514, 36.9%) or transferred (n=7703, 63.1%) to an
invasive hospital (A:5480; B:3621; C:3116) where 11,247 (92.1%) underwent
catheterization. Comorbidities and angiographic disease burden differed across
sites. Variation in 30-day revascularization (PCI: 71.3%, 72.0%, 68.7%, p<0.001;
CABG: 6.2%, 6.4%, 9.3%, p<0.001) and drug-eluting stent use for PCI (24.3%,
54.6%, 50.5%, p<0.001) were observed. After adjustment for patient demographics
and comorbidities, variation in rates of 1-year death or CV hospitalization was
observed among those with 30-day revascularization (p(interaction)<0.001; B
versus A: HR 0.78, 95%CI 0.66-0.91; C versus A: HR 0.77, 95%CI 0.65-0.91; B
versus C: HR 1.01, 95%CI 0.84-1.21). CONCLUSIONS: Despite a government funded
health system, we have shown variation in hospital treatment exists. Following
adjustment hospital site was associated with differences in clinical outcome
within 1year. Hence, further efforts may be warranted to help address potential
disparities in ACS care.
PMID- 28495249
TI - Heart rate variability to monitor performance in elite athletes: Criticalities
and avoidable pitfalls.
AB - BACKGROUND: Spectral analysis of Heart Rate Variability (HRV) is a simple, non
invasive technique that is widely used in sport to assess sympatho-vagal
regulation of the heart. Its employment is increasing partly due to the rising
usage of wearable devices. However data acquisition using these devices may be
suboptimal because they cannot discriminate between sinus and non-sinus beats and
do not record any data regarding respiratory frequency. This information is
mandatory for a correct clinical interpretation. METHODS: This study involved 974
elite athletes, all of them underwent a complete autonomic assessment, by way of
Autoregressive HRV analysis. RESULTS: In 91 subjects (9% of the total population)
we observed criticalities of either cardiac rhythm or respiration. Through
perusal of one-lead ECG analysis we observed that 77 subjects had atrial or
ventricular ectopy, i.e. conditions which impair stationarity and sinus rhythm.
Running anyway autonomic nervous system analysis in this population, we observed
that RR variance and raw values of LF and HF regions are significantly higher in
arrhythmic subjects. In addition 14 subjects had slow (about 6 breath/min, 0.1Hz)
respiration. This condition clouds the separation between LF from HF spectral
regions of RR interval variability, respectively markers of the prevalent
sympathetic and vagal modulation of SA node and of their synergistic interaction.
CONCLUSIONS: Caution must be payed when assessing HRV with non-ECG wearable
devices. Recording ECG signal and ensuring that respiratory rate is higher than
10 breath/min are both prerequisites for a more reliable analysis of HRV
particularly in athletes.
PMID- 28495250
TI - Austerity and its implications for immigrant health in France.
AB - The ongoing economic crisis in France increasingly has affected immigrant rights,
including access to health care. Consistent with a 2014 League Against Cancer
survey, we identify the ways in which sickness produces a "double penalty" for
immigrants with serious illness. Immigrants with chronic illnesses such as
cancer, diabetes, and other debilitating conditions divert vital funds from daily
needs to deal with sickness and loss of work while at the same time national
austerity measures shred the state's traditional safety net of social services
and support. We examine how immigrants strategize to manage financial exigencies,
therapeutic itineraries and social relations in the face of these converging
pressures. We base our findings on two studies related by this theme: an
investigation of health inequalities in the Medoc region, in which 88 women, 44
of North African and Eastern European origin, were interviewed over a three-year
period (2010-2013); and a three-year study (2014-2017) of West African immigrant
women with breast cancer seeking treatment in the greater Paris region, 70
members of immigrant associations, and clinical personnel in three hospitals.
PMID- 28495251
TI - Vector control: time for a planetary health approach.
PMID- 28495252
TI - Smoking status and HIV in low-income and middle-income countries.
PMID- 28495253
TI - Every breath you take....
PMID- 28495254
TI - Maternal hepatitis B virus infection and risk of preterm birth in China.
PMID- 28495255
TI - Women leaders in global health.
PMID- 28495256
TI - Research capacity building-obligations for global health partners.
PMID- 28495257
TI - The Lancet Global Health Commission on High Quality Health Systems-where's the
complexity?
PMID- 28495258
TI - The Lancet Global Health Commission on High Quality Health Systems-where's the
complexity? - Authors' reply.
PMID- 28495259
TI - Unreliable estimation of prevalence of fetal alcohol syndrome.
PMID- 28495260
TI - Unreliable estimation of prevalence of fetal alcohol syndrome.
PMID- 28495261
TI - Unreliable estimation of prevalence of fetal alcohol syndrome - Authors' reply.
PMID- 28495262
TI - Access to Chagas disease treatment in non-endemic countries: the case of Spain.
PMID- 28495263
TI - Tobacco use among people living with HIV: analysis of data from Demographic and
Health Surveys from 28 low-income and middle-income countries.
AB - BACKGROUND: Tobacco use among people living with HIV results in excess morbidity
and mortality. However, very little is known about the extent of tobacco use
among people living with HIV in low-income and middle-income countries (LMICs).
We assessed the prevalence of tobacco use among people living with HIV in LMICs.
METHODS: We used Demographic and Health Survey data collected between 2003 and
2014 from 28 LMICs where both tobacco use and HIV test data were made publicly
available. We estimated the country-specific, regional, and overall prevalence of
current tobacco use (smoked, smokeless, and any tobacco use) among 6729 HIV
positive men from 27 LMICs (aged 15-59 years) and 11 495 HIV-positive women from
28 LMICs (aged 15-49 years), and compared them with those in 193 763 HIV-negative
men and 222 808 HIV-negative women, respectively. We estimated prevalence
separately for males and females as a proportion, and the analysis accounted for
sampling weights, clustering, and stratification in the sampling design. We
computed pooled regional and overall prevalence estimates through meta-analysis
with the application of a random-effects model. We computed country, regional,
and overall relative prevalence ratios for tobacco smoking, smokeless tobacco
use, and any tobacco use separately for males and females to study differences in
prevalence rates between HIV-positive and HIV-negative individuals. FINDINGS: The
overall prevalence among HIV-positive men was 24.4% (95% CI 21.1-27.8) for
tobacco smoking, 3.4% (1.8-5.6) for smokeless tobacco use, and 27.1% (22.8-31.7)
for any tobacco use. We found a higher prevalence in HIV-positive men of any
tobacco use (risk ratio [RR] 1.41 [95% CI 1.26-1.57]) and tobacco smoking (1.46
[1.30-1.65]) than in HIV-negative men (both p<0.0001). The difference in
smokeless tobacco use prevalence between HIV-positive and HIV-negative men was
not significant (1.26 [1.00-1.58]; p=0.050). The overall prevalence among HIV
positive women was 1.3% (95% CI 0.8-1.9) for tobacco smoking, 2.1% (1.1-3.4) for
smokeless tobacco use, and 3.6% (95% CI 2.3-5.2) for any tobacco use. We found a
higher prevalence in HIV-positive women of any tobacco use (RR 1.36 [95% CI 1.10
1.69]; p=0.0050), tobacco smoking (1.90 [1.38-2.62]; p<0.0001), and smokeless
tobacco use (1.32 [1.03-1.69]; p=0.030) than in HIV-negative women.
INTERPRETATION: The high prevalence of tobacco use in people living with HIV in
LMICs mandates targeted policy, practice, and research action to promote tobacco
cessation and to improve the health outcomes in this population. FUNDING: South
African Medical Research Council and the UK Medical Research Council.
PMID- 28495264
TI - Community engagement and integrated health and polio immunisation campaigns in
conflict-affected areas of Pakistan: a cluster randomised controlled trial.
AB - BACKGROUND: Pakistan faces huge challenges in eradicating polio due to widespread
poliovirus transmission and security challenges. Innovative interventions are
urgently needed to strengthen community buy-in, to increase the coverage of oral
polio vaccine (OPV) and other routine immunisations, and to enhance immunity
through the introduction of inactivated polio vaccine (IPV) in combination with
OPV. We aimed to evaluate the acceptability and effect on immunisation coverage
of an integrated strategy for community engagement and maternal and child health
immunisation campaigns in insecure and conflict-affected polio-endemic districts
of Pakistan. METHODS: We did a community-based three-arm cluster randomised trial
in healthy children aged 1 month to 5 years that resided within the study sites
in three districts of Pakistan at high risk of polio. Clusters were randomly
assigned by a computer algorithm using restricted randomisation in blocks of 20
by an external statistician (1:1:1) to receive routine polio programme activities
(control, arm A), additional interventions with community outreach and
mobilisation using an enhanced communication package and provision of short-term
preventive maternal and child health services and routine immunisation (health
camps), including OPV (arm B), or all interventions of arm B with additional
provision of IPV delivered at the maternal and child health camps (arm C). An
independent team conducted surveys at baseline, endline, and after each round of
supplementary immunisation activity for acceptability and effect. The primary
outcome measures for the study were coverage of OPV, IPV, and routine extended
programme on immunisation vaccines and changes in the proportion of unvaccinated
and fully vaccinated children. This trial is registered with ClinicalTrials.gov,
number NCT01908114. FINDINGS: Between June 4, 2013, and May 31, 2014, 387
clusters were randomised (131 to arm A, 127 to arm B, and 129 to arm C). At
baseline, 28 760 children younger than 5 years were recorded in arm A, 30 098 in
arm B, and 29 126 in arm C. 359 clusters remained in the trial until the end (116
in arm A, 120 in arm B, and 123 in arm C; with 23 334 children younger than 5
years in arm A, 26 110 in arm B, and 25 745 in arm C). The estimated OPV coverage
was 75% in arm A compared with 82% in arm B (difference vs arm A 6.6%; 95% CI 4.8
8.3) and 84% in arm C (8.5%, 6.8-10.1; overall p<0.0001). The mean proportion of
routine vaccine doses received by children younger than 24 months of age was 43%
in arm A, 52% in arm B (9%, 7-11) and 54% in arm C (11%, 9-13; overall p<0.0001).
No serious adverse events requiring hospitalisation were reported after
immunisation. INTERPRETATION: Despite the challenges associated with the polio
end-game in high-risk, conflict-affected areas of Pakistan, a strategy of
community mobilisation and targeted community-based health and immunisation camps
during polio immunisation campaigns was successful in increasing vaccine
coverage, including polio vaccine coverage. FUNDING: Bill & Melinda Gates
Foundation.
PMID- 28495265
TI - Continuous positive airway pressure for children with undifferentiated
respiratory distress in Ghana: an open-label, cluster, crossover trial.
AB - BACKGROUND: In low-income and middle-income countries, invasive mechanical
ventilation is often not available for children at risk of death from respiratory
failure. We aimed to determine if continuous positive airway pressure (CPAP), a
form of non-invasive ventilation, decreases all-cause mortality in children with
undifferentiated respiratory distress in Ghana. METHODS: This open-label,
cluster, crossover trial was done in two Ghanaian non-tertiary hospitals where
invasive mechanical ventilation is not routinely available. Eligible participants
were children aged from 1 month to 5 years with a respiratory rate of more than
50 breaths per min in children 1-12 months old, or more than 40 breaths per min
in children older than 12 months, and use of accessory muscles or nasal flaring.
CPAP machines were allocated to one hospital during each study block, while the
other hospital served as the control site. The initial intervention site was
randomly chosen using a coin toss. 5 cm of water pressure was delivered via CPAP
nasal prongs. The primary outcome measure was all-cause mortality rate at 2 weeks
after enrolment in patients for whom data were available after 2 weeks. We also
did post-hoc regression analysis and subgroup analysis of children by malaria
status, oxygen saturation, and age. This study is registered with
ClinicalTrials.gov, number NCT01839474. FINDINGS: Between Jan 20, 2014, and Dec
5, 2015, 2200 children were enrolled: 1025 at the intervention site and 1175 at
the control site. Final analysis included 1021 patients in the CPAP group and
1160 patients in the control group. 2 weeks after enrolment, 26 (3%) of 1021
patients in the CPAP group, and 44 (4%) of 1160 patients in the control group,
had died (relative risk [RR] of mortality 0.67, 95% CI 0.42-1.08; p=0.11). In
children younger than 1 year, all-cause mortality was ten (3%) of 374 patients in
the CPAP group, and 24 (7%) of 359 patients in the control group (RR 0.40, 0.19
0.82; p=0.01). After adjustment for study site, time, and clinically important
variables, the odds ratio for 2-week mortality in the CPAP group versus the
control group was 0.4 in children aged up to 6 months, 0.5 for children aged 12
months, 0.7 for children aged 24 months, and 1.0 for those aged 36 months. 28
patients (3%) in the CPAP group and 24 patients (2%) in the control group had
CPAP-related adverse events, such as vomiting, aspiration, and nasal, skin, or
eye trauma. No serious adverse events were observed. INTERPRETATION: In the
unadjusted analysis the use of CPAP did not decrease all-cause 2-week mortality
in children 1 month to 5 years of age with undifferentiated respiratory distress.
After adjustment for study site, time, and clinically important variables, 2-week
mortality in the CPAP group versus the control group was significantly decreased
in children 1 year of age and younger. CPAP is safe and improves respiratory rate
in a non-tertiary setting in a lower-middle-income country. FUNDING: General
Electric Foundation.
PMID- 28495266
TI - Maternal pre-pregnancy infection with hepatitis B virus and the risk of preterm
birth: a population-based cohort study.
AB - BACKGROUND: Preterm birth is the leading cause of child death in children younger
than 5 years. Large cohort studies in developed countries have shown that
maternal hepatitis B virus infection is associated with preterm birth, but there
is little reliable evidence from China and other developing countries, where
hepatitis B virus prevalence is intermediate or high. Hence, we designed this
study to investigate the association between pre-pregnancy hepatitis B virus
infection and risk of preterm and early preterm birth. METHODS: Between Jan 1,
2010, and Dec 31, 2012, we did a population-based cohort study using data from
489 965 rural women aged 21-49 years who had singleton livebirths from 220
counties of China who participated in the National Free Preconception Health
Examination Project. Participants were divided into three groups according to
their pre-pregnancy status of hepatitis B virus infection: women uninfected with
hepatitis B virus (control group), women who were HBsAg positive and HBeAg
negative (exposure group 1), and women who were both HBsAg and HBeAg positive
(exposure group 2). The primary outcome was preterm birth (gestation at less than
37 weeks). We used log-binomial regression to estimate adjusted risk ratios (aRR)
of preterm birth for women with pre-pregnancy hepatitis B virus infection, and
risk of early preterm birth (gestation less than 34 weeks). FINDINGS: 489 965
women met inclusion criteria and were included in this study; of these, 20 827
(4.3%) were infected with hepatitis B virus. Compared with women who were not
infected with hepatitis B virus, women who were HBsAg positive and HBeAg negative
had a 26% higher risk of preterm birth (aRR 1.26, 95% CI 1.18-1.34) and women who
were both HBsAg and HBeAg positive had a 20% higher risk of preterm birth (aRR
1.20, 1.08-1.32). Compared with women who were not infected with hepatitis B
virus, women who were HBsAg positive and HBeAg negative manifested an 18% higher
risk of early preterm birth (gestation less than 34 weeks; aRR 1.18, 1.04-1.34)
and women who were both HBsAg and HBeAg positive had a 34% higher risk of early
preterm birth (aRR 1.34, 1.10-1.61). Maternal pre-pregnancy hepatitis B virus
infection was independently associated with higher risk of preterm birth and
early preterm birth. These associations were similar in subgroups of participants
as defined by baseline characteristics. INTERPRETATION: Besides mother-to-child
transmission, the risk of preterm birth in women infected with hepatitis B virus
should not be neglected. Comprehensive programmes that focus on early detection
of hepatitis B virus infection before pregnancy and provide appropriate medical
intervention for women infected with hepatitis B virus before and during
pregnancy would be helpful in improving maternal and neonatal outcomes and
reducing child mortality. FUNDING: Chinese Association of Maternal and Child
Health Studies.
PMID- 28495267
TI - The Evolutionary Interplay between Adaptation and Self-Fertilization.
AB - Genome-wide surveys of nucleotide polymorphisms, obtained from next-generation
sequencing, have uncovered numerous examples of adaptation in self-fertilizing
organisms, especially regarding changes to climate, geography, and reproductive
systems. Yet existing models for inferring attributes of adaptive mutations often
assume idealized outcrossing populations, which risks mischaracterizing
properties of these variants. Recent theoretical work is emphasizing how various
aspects of self-fertilization affects adaptation, yet empirical data on these
properties are lacking. We review theoretical and empirical studies demonstrating
how self-fertilization alters the process of adaptation, illustrated using
examples from current sequencing projects. We propose ideas for how future
research can more accurately quantify aspects of adaptation in self-fertilizers,
including incorporating the effects of standing variation, demographic history,
and polygenic adaptation.
PMID- 28495268
TI - The presence of VEGF and Notch2 during preantral-antral follicular transition in
infantile rats: Anatomical evidence and its implications.
AB - Folliculogenesis is a process that depends on angiogenesis, in which VEGF and
Notch signaling pathway members are involved. Although this pathway is present in
preantral and antral follicular structures during the second stage of
folliculogenesis, this association has not been described. Therefore, this study
aimed to identify VEGF and Notch2 in ovary structures of infantile rats after
induction of follicular development with a gonadotropin stimulus. In order to
explore this possibility we analyzed rat ovary morphology from days 10-25 after
birth; subsequently, the transition from preantral follicle to an antral stage
was analyzed by the induction of follicular development with equine chorionic
gonadotropin (eCG) and VEGF and Notch were identified in the rat ovary by
fluorescence. The histological analysis revealed that the ovary of a 10-day-old
rat has the highest percentage of preantral follicles and based on this a 10IU
eCG dose promoted an increase in the number of antral follicles, as well as a
decrease in the number of preantral follicles, related to which there was an
increase in ovary weight and size. In addition, a higher concentration of
circulating estradiol was observed, proliferation of granulosa cells in both
follicle groups was stimulated, and the accumulation of VEGF in granulosa and
theca cells and in the antral follicle oocyte was increased (p<0.05), whereas the
presence of Notch2 was limited to mural granulosa cells, in granulosa cells that
formed the cumulus oophorus and in the oocyte of both groups of follicles. The
multiple correspondence analysis allowed us to support an association between
VEGF and Notch2 during the transition from preantral to antral follicles in the
ovary of an infantile rat.
PMID- 28495269
TI - Identification of novel regulatory GRE-binding elements in the porcine IP3R1 gene
promoter and their transcriptional activation under glucocorticoid stimulation.
AB - Inositol 1,4,5-trisphosphate receptor 1 (IP3R1) is a type of ligand-gated calcium
channel that is expressed predominantly in mammalian skeletal muscle, where it
acts as a key regulator of calcium homeostasis. In meat, calcium disequilibrium
is accompanied by the deterioration of meat quality. Here we show that serum
cortisol concentration was higher and the IP3R1 gene expression level increased
markedly in pigs exposed to high stress. In porcine primary muscle cells,
dexamethasone (DEX, a synthetic glucocorticoid) increased the protein levels of
porcine IP3R1 and GRalpha, and cell apoptosis, and the specific GRalpha inhibitor
RU486 attenuated these effects. DEX also increased the expression of IP3R1 at
both the gene and protein levels, and this expression was attenuated by RU486,
siRNA against GRalpha, and the transcriptional inhibitor actinomycin D. DEX
significantly reduced cell viability and increased the intracellular calcium
concentration, and these effects were attenuated by siRNA against GRalpha.
Bioinformatics analyses predicted a potential glucocorticoid response element
(GRE) located in the region -326 to -309 upstream of the IP3R1 promoter and
highly conserved in pigs and other mammalian species. Promoter analysis showed
that this region containing the GRE was critical for transcriptional activity of
porcine IP3R1 under DEX stimulation. This was confirmed by deletion and site
mutation methods. EMSA and ChIP assays showed that this potential GRE bound
specifically to GRalpha and this complex activated the transcription of the IP3R1
gene. Taken together, these data suggest that DEX-mediated induction of IP3R1
influences porcine muscle cells through the transcriptional activation of a
mechanism involving interactions between GRalpha and a GRE present in the
proximal IP3R1 promoter. This process can lead to an imbalance in intracellular
calcium concentration, which may subsequently activate the apoptosis signal and
decrease cell activity, and cause deterioration of meat quality.
PMID- 28495270
TI - Egg deposition of maternal testosterone is primarily controlled by the
preovulatory peak of luteinizing hormone in Japanese quail.
AB - Differential transfer of maternal testosterone (T) into egg yolk provides a means
of adjusting an offspring's phenotype to ambient environmental conditions. While
the environmental and genetic driven variability in yolk T levels is widely
described, the underlying mechanisms are poorly understood. Here, we investigated
whether neuroendocrine mechanisms controlling ovulatory processes are associated
with the regulation of yolk T deposition. Circulatory profiles of luteinizing
hormone (LH), T and estradiol levels were analysed during the last 7h before
ovulation in Japanese quail selected for contrasting yolk T concentrations.
Moreover, the pituitary responsiveness to a single challenge with gonadotropin
releasing hormone (GnRH) was evaluated. High egg T (HET) birds displayed higher
concentrations of LH at 3.5h before ovulation than low egg T (LET) birds while no
differences were found around the time of expected ovulation. The pre-ovulatory
profile of T and estradiol levels did not differ between LET and HET females but
pre-ovulatory plasma T positively correlated with LH concentrations at 6.5h and
3.5h before ovulation. The LH response to GnRH did not differ between LET and HET
females. Our results demonstrate that the pre-ovulatory LH surge can determine
the amount of T transferred into the egg yolk. This link between yolk T
deposition and the ovulatory cycle driven variation of reproductive hormones may
explain balance between the effects of circulating T on female's reproductive
physiology and yolk T on offspring phenotype.
PMID- 28495271
TI - The melanocortin-2 receptor of the rainbow trout: Identifying a role for critical
positions in transmembrane domain 4, extracellular loop 2, and transmembrane
domain 5 in the activation of rainbow trout MC2R.
AB - The activation of either teleost or tetrapod melanocortin-2 receptor (MC2R)
orthologs requires interaction between the HFRW motif and R/KKRRP motif in the
primary sequence of ACTH, and two corresponding sites on the melanocortin 2
receptor. While the HFRW contact site on MC2R appears to involve residues in TM2,
TM3, and TM6, several studies on human MC2R point to the EC2/TM5 region of MC2R
as a possible location for the R/KKRRP contact site. In this study nineteen
single-alanine mutants of rainbow trout (rt) MC2R were made beginning at V153 in
TM4, at all positions in EC2 (extracellular loop 2), to F175 in TM5. For twelve
of these alanine mutants (i.e., V153, G155, C162, D163, T165, V166, I167, H169,
F170, H172, V173, L174), alanine substitution did not have a statistically
significant effect on activation of the receptor. For four of these alanine
mutations (i.e., V157, M158, F161, K168), while the negative shift in ligand
sensitivity was statistically significant, the magnitude of the negative shift in
activation was fivefold or less. However, for substitution at V159 in TM4
(negative shift in activation: 110 fold), F171 in TM5 (negative shift in
activation: 48-fold), and F175 in TM5 (negative shift in activation: 100 fold),
the effect on activation was both statistically significant and may be
physiologically relevant. To support this conclusion, a triple alanine mutant of
rtMC2R (V159/A, F171/A, F175/A), and this mutant receptor could not be activated
by ACTH at concentrations as high as 10-6M. A Cell Surface ELISA analysis
indicated that the trafficking of the triple alanine mutant rtMC2R to the plasma
membrane was not impaired by the alanine substitutions. Collectively, these
observations point to a critical role for TM4 and TM5 in the activation of the
rainbow trout melanocortin-2 receptor.
PMID- 28495272
TI - Pannexins in vision, hearing, olfaction and taste.
AB - In mammals, the pannexin gene family consists of three members (Panx1, 2, 3),
which represent a class of integral membrane channel proteins sharing some
structural features with chordate gap junction proteins, the connexins. Since
their discovery in the early 21st century, pannexin expression has been detected
throughout the vertebrate body including eye, ear, nose and tongue, making the
investigation of the roles of this new class of channel protein in health and
disease very appealing. The localization in sensory organs, coupled with unique
channel properties and associations with major signaling pathways make Panx1, and
its relative's, significant contributors for fundamental functions in sensory
perception. Until recently, cell-based studies were at the forefront of pannexin
research. Lately, the availability of mice with genetic ablation of pannexins
opened new avenues for testing pannexin functions and behavioural phenotyping.
Although we are only at the beginning of understanding the roles of pannexins in
health and disease, this review summarizes recent advances in elucidating the
various emerging roles pannexins play in sensory systems, with an emphasis on
unresolved conflicts.
PMID- 28495273
TI - The Key of the Maze: The role of mental imagery and cognitive flexibility in
navigational planning.
AB - Spatial navigation planning ability relies on both mental imagery and cognitive
flexibility. Considering the importance of planning ability in everyday life,
several neuropsychological tests are used in clinical practice for its
assessment, although some of these are not aimed at assessing the strategies of
navigational planning. The Porteus Maze Test (PMT) and the Key Search Task (KST)
require to plan a strategy in a maze and in an imagined space, respectively. To
the best of our knowledge, although these two tests share some features, the
relationship between them has never been explored. The purpose of the present
study was to investigate, for the first time, the relationship between the PMT
and the KST performances in 38 healthy subjects in order to understand the
implications of this association for the assessment of spatial navigation
ability. Subjects were subdivided in bad or good navigation planners on the basis
of the their KST score. The results of the study have revealed a significant
difference (t=2.35; p=0.03) in the number of errors made at the PMT by bad
navigational planners (0.78+/-0.28) and good navigational planners (0.10+/-0.06).
The first group (bad navigational planners) made more errors at the PMT than the
good navigational planners (who made less errors at the PMT). This provides
evidence of the possibility to use the KST and the PMT in a combined way as a new
tool for the assessment of spatial navigational planning ability. Furthermore,
this finding highlights the importance of mental imagery and cognitive
flexibility in spatial navigation, suggesting that these functions could be the
link between a good planning ability and a successful spatial navigation. In
conclusion, this study suggests that an efficient navigation would not be
possible without a good navigational planning ability.
PMID- 28495274
TI - Females are sensitive to unpleasant human emotions regardless of the emotional
context of photographs.
AB - Previous studies have demonstrated that females exhibit higher sensitivity than
males to the emotional state of a person in a photograph. The present study
examined whether such females' sensitivity to human emotions could be observed
even when the background emotional contexts were incongruent with facial
expressions. The late positive potential (LPP) was measured while 19-female and
15-male participants viewed a photograph of a face with varied emotional
expressions (pleasant, neutral, or unpleasant) superimposed on a background
photograph with varied valences (pleasant, neutral, or unpleasant). The results
showed that unpleasant background photographs elicited a larger LPP compared to
pleasant and neutral background photographs in both female and male participants.
In contrast, a larger LPP for the unpleasant face photographs was observed only
in female participants. Furthermore, the effect of face photographs did not
interact with the effect of background photographs. These results suggest that
females are sensitive to human emotions regardless of the emotional context.
PMID- 28495275
TI - Cancer risk paradox: grand plans fall short?
PMID- 28495276
TI - Immune checkpoint inhibitors in malignant pleural mesothelioma.
PMID- 28495277
TI - Poorly specified fasting conditions in clinical research could lead to treatment
failure.
PMID- 28495278
TI - Engaging specialist oncologists in the assessment of oncology drugs in Canada.
PMID- 28495279
TI - Beauties of the Night.
PMID- 28495280
TI - Sentinel-lymph-node mapping in endometrial cancer.
PMID- 28495281
TI - Sentinel-lymph-node mapping in endometrial cancer.
PMID- 28495282
TI - Sentinel-lymph-node mapping in endometrial cancer - Authors' reply.
PMID- 28495283
TI - Molecular diagnoses of century-old childhood tumours.
PMID- 28495284
TI - Genomic biomarkers for precision radiation medicine.
PMID- 28495285
TI - Genomic biomarkers for precision radiation medicine - Authors' reply.
PMID- 28495286
TI - Widening the gap: additional concerns with crowdfunding in health care.
PMID- 28495287
TI - Peri-operative chemotherapy with or without bevacizumab in operable
oesophagogastric adenocarcinoma.
PMID- 28495288
TI - Peri-operative chemotherapy with or without bevacizumab in operable
oesophagogastric adenocarcinoma.
PMID- 28495289
TI - Peri-operative chemotherapy with or without bevacizumab in operable
oesophagogastric adenocarcinoma - Authors' reply.
PMID- 28495290
TI - Correction to Lancet Oncol 2017; 18: e186.
PMID- 28495291
TI - Mid-face bone destruction involving the palate.
PMID- 28495292
TI - The living organism: Strengthening the basis.
AB - In spite of the considerable amount of literature dedicated to the living
organism, it retains its mysteries. One of the most discussed aspects nowadays is
whether the term "cognition" can be attributed to all classes of organisms, or
whether it only refers to a metaphoric use of one human reality. Our approach
consists of retaining the term "cognition" and making it a technical term, in
order to propose a generic model. In this way, cognition becomes what finally
characterises an organism as an autonomous agent. This perspective eliminates
some misplaced questions, and helps to reframe old ones. The cognitive dimension
can be apprehended indirectly only through its appearances. These direct us
towards a modular model of cognition and orientate research towards the
clarification of specific modules for each class of organisms.
PMID- 28495293
TI - [How to organize hospital discharge after COPD exacerbation?]
PMID- 28495294
TI - [Which inhaled pharmacological treatment during acute COPD exacerbation in
community-based practice?]
PMID- 28495295
TI - [Guidelines to integrate palliative management in patients with acute COPD
exacerbation].
PMID- 28495297
TI - [Non-pharmacological management in acute COPD exacerbations].
PMID- 28495296
TI - [Non-pharmacological management of acute COPD exacerbations in community-based
practice].
PMID- 28495298
TI - [Antibiotics during acute COPD exacerbations].
PMID- 28495299
TI - A randomized comparison of a novel nitinol-frame low-dose-copper intrauterine
contraceptive and a copper T380S intrauterine contraceptive.
AB - OBJECTIVE: We sought to compare VeraCept (VC175), a novel nitinol intrauterine
contraceptive (IUC) with 175 square-mm of copper surface area, to a copper T380S
IUC. STUDY DESIGN: We enrolled parous women into a randomized subject-blinded
comparison of VC175 and a copper T380S in a 2:1 fashion at a single clinic. The
primary outcomes were total adverse events and continuation at 12 months. We also
examined pain on insertion, ease of placement, expulsion, tolerability and
pregnancy. Subjective ratings were on a 5-point Likert scale (0, no pain to 5,
worst pain). We followed subjects through 24-month follow-up. RESULTS: We
enrolled 300 women with 199 randomized to VC175 and 101 to the T380S. Insertion
was successful in 198 subjects for VC175 and 100 for the T380S. Mean age was 25
years (range 18, 41), and median parity was 2 (range 1, 8), with 39% having only
had Cesarean deliveries. No subjects developed clinical infection or reported
serious adverse events. In the VC175 and T380S groups, mean pain at insertion was
1.4 and 2.4, respectively (p<.01). At the 12-month primary endpoint for VC175 and
T380S, respectively, continuation was 84% and 68% (p<.002) with expulsions in
5.0% and 12.0% (p<.05) and removal for pain/bleeding in 3.5% and 17.0% (p<.01).
At the 24-month visit for VC175 and T380S, respectively, continuation was 77% and
62% (p<.02 by log-rank). One ectopic pregnancy was identified at the 12-month
follow-up in a VC175 user. No other pregnancies were diagnosed. With 297.3 and
132.4 woman-years, pregnancy rates were 0.3 and 0.0 per 100 woman-years for VC175
and T380S, respectively. CONCLUSIONS: VC175 resulted in less pain at insertion,
fewer expulsions and higher total continuation than the T380S, with similar
contraceptive efficacy. IMPLICATIONS: VC175 is a promising new intrauterine
copper contraceptive on a nitinol frame that warrants further clinical trials.
PMID- 28495300
TI - Aortic Valve Stenosis Increases Helical Flow and Flow Complexity: A Study of
Intra-Operative Cardiac Vector Flow Imaging.
AB - Aortic valve stenosis alters blood flow in the ascending aorta. Using intra
operative vector flow imaging on the ascending aorta, secondary helical flow
during peak systole and diastole, as well as flow complexity of primary flow
during systole, were investigated in patients with normal, stenotic and replaced
aortic valves. Peak systolic helical flow, diastolic helical flow and flow
complexity during systole differed between the groups (p < 0.0001), and
correlated to peak systolic velocity (R = 0.94, 0.87 and 0.88, respectively). The
study indicates that aortic valve stenosis increases helical flow and flow
complexity, which are measurable with vector flow imaging. For assessment of
aortic stenosis and optimization of valve surgery, vector flow imaging may be
useful.
PMID- 28495301
TI - 2017 ISHNE-HRS expert consensus statement on ambulatory ECG and external cardiac
monitoring/telemetry.
AB - Ambulatory ECG (AECG) is very commonly employed in a variety of clinical contexts
to detect cardiac arrhythmias and/or arrhythmia patterns which are not readily
obtained from the standard ECG. Accurate and timely characterization of
arrhythmias is crucial to direct therapies that can have an important impact on
diagnosis, prognosis or patient symptom status. The rhythm information derived
from the large variety of AECG recording systems can often lead to appropriate
and patient-specific medical and interventional management. The details in this
document provide background and framework from which to apply AECG techniques in
clinical practice, as well as clinical research.
PMID- 28495302
TI - Optically stimulated luminescence of natural NaCl mineral from Dead Sea exposed
to gamma radiation.
AB - In this work, the continuous wave - optically stimulated luminescence (CW-OSL)
emissions of natural salt minerals, collected from Dead Sea in summer of 2015,
were studied. The CW-OSL dose response of natural salt showed a linear range
between 0.5Gy and 10Gy of gamma radiation of 60Co. Samples exposed at 3Gy
exhibited good repeatability with a variation coefficient of 4.6%. The CW-OSL
response as function of the preheating temperature (50-250 degrees C) was
analyzed. An increase of 15% of the CW-OSL response was observed in NaCl samples
during storage period of 336h. The results showed that the natural Dead Sea salt
minerals could be applied as natural dosimeter of gamma radiation.
PMID- 28495303
TI - The characteristics of salivary pepsin in patients with severe motor and
intellectual disabilities.
AB - PURPOSE: The aim of the present study was to determine the utility of measuring
the salivary pepsin level (SPL) as an objective assessment of gastroesophageal
reflux disease (GERD) in severe motor and intellectual disabilities (SMID)
patients. SUBJECTS AND METHODS: This prospective study included 26 SMID patients
who underwent simultaneous 24-h multichannel intraluminal impedance pH
measurement (pH/MII) and SPL evaluation. The enrolled patients were divided into
GERD (+) or GERD (-) groups according to the pH/MII findings. The age, gender and
pH/MII parameters were compared between the two groups. A correlation analysis
was also conducted for the SPL following early-morning fasting and post-enteral
feeding and the age, gender, presence of gastrostomy and tracheostomy and pH/MII
parameters. The SPL was compared between the two sampling groups. RESULTS:
Fifteen patients were classified as GERD (+), and 11 patients were classified as
GERD (-). The mean SPL following early-morning fasting and post-enteral feeding
among all patients were 104.3 (median: 38, 25th and 75th percentile: 12, 361)
ng/ml and 222.2 (median: 152:0, 500) ng/ml, respectively. Regarding positivity,
76.9% and 73.1% of SPL values in early-morning fasting and post-enteral feeding
SMID patients, respectively, were positive (?16ng/ml). The SPL following early
morning fasting demonstrated a weak but significant positive correlation with
age. In contrast, we noted no correlation between the pH/MII parameters and the
SPL for either the early-morning fasting or post-enteral feeding patients, and no
significant difference in the SPL was observed between the GERD (+) and (-)
patients. CONCLUSIONS: The present study showed that a high proportion of SMID
patients had a relatively high SPL, regardless of the presence of GERD. The SPL
in SMID patients might be affected by several distinctive factors in addition to
gastroesophageal reflux.
PMID- 28495304
TI - [Large cervicodorsal epidural abscess].
PMID- 28495305
TI - Mechanism for optimization of signal-to-noise ratio of dopamine release based on
short-term bidirectional plasticity.
AB - Repeated electrical stimulation of dopamine (dopamine) fibers can cause variable
effects on further dopamine release; sometimes there are short-term decreases
while in other cases short-term increases have been reported. Previous studies
have failed to discover what factors determine in which way dopamine neurons will
respond to repeated stimulation. The aim of the present study was therefore to
investigate what determines the direction and magnitude of this particular form
of short-term plasticity. Fixed potential amperometry was used to measure
dopamine release in the nucleus accumbens in response to two trains of electrical
pulses administered to the ventral tegmental area of anesthetized mice. When the
pulse trains were of equal magnitude we found that low magnitude stimulation was
associated with short-term suppression and high magnitude stimulation with short
term facilitation of dopamine release. Secondly, we found that the magnitude of
the second pulse train was critical for determining the sign of the plasticity
(suppression or facilitation), while the magnitude of the first pulse train
determined the extent to which the response to the second train was suppressed or
facilitated. This form of bidirectional plasticity might provide a mechanism to
enhance signal-to-noise ratio of dopamine neurotransmission.
PMID- 28495306
TI - Long-term effects of enriched environment following neonatal hypoxia-ischemia on
behavior, BDNF and synaptophysin levels in rat hippocampus: Effect of combined
treatment with G-CSF.
AB - Increasing evidence shows that exposure to an enriched environment (EE) is
neuroprotective in adult and neonatal animal models of brain ischemia. However,
the mechanisms underlying this effect remain unclear. The aim of the current
study was to investigate whether post-weaning EE would be effective in preventing
functional deficits and brain damage by affecting markers of synaptic plasticity
in a neonatal rat model of hypoxia-ischemia (HI). We also examined the
possibility that granulocyte-colony stimulating factor (G-CSF), a growth factor
with known neuroprotective effects in a variety of experimental brain injury
models, combined with EE stimulation could enhance the potential beneficial
effect of EE. Seven-day-old Wistar rats of either sex were subjected to permanent
ligation of the left common carotid artery followed by 60min of hypoxia (8% O2)
and immediately after weaning (postnatal day 21) were housed in enriched
conditions for 4weeks. A group of enriched-housed rats had been treated with G
CSF immediately after HI for 5 consecutive days (50MUg/kg/day). Behavioral
examination took place approximately at three months of age and included
assessments of learning and memory (Morris water maze) as well as motor
coordination (Rota-Rod). Infarct size and hippocampal area were estimated
following behavioral assessment. Synaptic plasticity was evaluated based on BDNF
and synaptophysin expression in the dorsal hippocampus. EE resulted in recovery
of post-HI motor deficits and partial improvement of memory impairments which was
not accompanied by reduced brain damage. Increased synaptophysin expression was
observed in the contralateral to carotid ligation hemisphere. Hypoxia-ischemia
alone or followed by enriched conditions did not affect BDNF expression which was
increased only in enriched-housed normal rats. The combined therapy of G-CSF and
EE further enhanced cognitive function compared to EE provided as monotherapy and
prevented HI-induced brain damage by altering synaptic plasticity as reflected by
increased synaptophysin expression. The above findings demonstrate that
combination of neuroprotective treatments may result in increased protection and
it might be a more effective strategy for the treatment of neonatal hypoxic
ischemic brain injury.
PMID- 28495307
TI - Event-related potentials during encoding: Comparing unitization to relational
processing.
AB - Context details are typically encoded into episodic memory via arbitrary
associations to the relevant item, known as relational binding. Subsequent
retrieval of those context details is primarily supported by recollection.
Research suggests that context retrieval can rely on familiarity if the context
details are "unitized" and thereby encoded as features of the item itself in a
single new representation. With most investigations into unitization focusing on
the contributions of familiarity and recollection during retrieval, little is
known about unitization during encoding. In an effort to begin understanding
unitization as an encoding process, we used event-related potentials to monitor
brain activity while participants were instructed to encode words with color
information using relational association or unitization. Results showed that
unitization-based encoding elicited significantly more negative potentials in the
left parietal region than relational encoding during presentation of the second
segment of strategically-specific sentences. This difference continued through
presentation of the third sentence segment, becoming less lateralized, and ended
before the final two segments were presented. During the mental imagery period,
unitization-based encoding elicited significantly more positive potentials than
relational encoding in the first 200ms centrally and from 400 through 1000ms in
left fronto-temporal and parieto-occipital regions. Our findings indicate that
unitization and relational processing diverged at approximately the time that the
context item was presented in the relational condition. During mental imagery,
unitization diverged from relational processing immediately, suggesting that
unitization affected the nature of the item representation, and possibly the
brain regions involved, during memory encoding.
PMID- 28495308
TI - Pharmaceutical prospects of naturally occurring quinazolinone and its
derivatives.
AB - Quinazolinones belong to a family of heterocyclic nitrogen compounds that have
attracted increasing interest because of their broad spectrum of biological
functions. This review describes three types of natural quinazolinones and their
synthesized derivatives and summarizes their various pharmacological activities,
including antifungal, anti-tumor, anti-malaria, anticonvulsant, anti-microbial,
anti-inflammatory and antihyperlipidemic activities. In addition, structure
activity relationships of quinazolinone derivatives are also reviewed.
PMID- 28495309
TI - Group II introns in wheat mitochondria have degenerate structural features and
varied splicing pathways.
AB - Mitochondrial introns in flowering plant genes are virtually all classified as
members of the group II ribozyme family although certain structural features have
degenerated to varying degrees over evolutionary time. We are interested in the
impact that unconventional intron architecture might have on splicing
biochemistry in vivo and we have focused in particular on intronic domains V and
VI, which for self-splicing introns provide a key component of the catalytic core
and the bulged branchpoint adenosine, respectively. Notably, the two
transesterification steps in classical group II splicing are the same as for
nuclear spliceosomal introns and release the intron as a lariat. Using RT-PCR and
circularized RT-PCR, we had previously demonstrated that several wheat
mitochondrial introns which lack a branchpoint adenosine have atypical splicing
pathways, and we have now extended this analysis to the full set of wheat
introns, namely six trans-splicing and sixteen cis-splicing ones. A number of
introns are excised using non-lariat pathways and interestingly, we find that
several introns which do have a conventional domain VI also use pathways that
appear to exploit other internal or external nucleophiles, with the lariat form
being relatively minor. Somewhat surprisingly, several introns with weakly
structured domain V/VI helices still exhibit classical lariat splicing,
suggesting that accessory factors aid in restoring a splicing-competent
conformation. Our observations illustrate that the loss of conventional group II
features during evolution is correlated with altered splicing biochemistry in an
intron-distinctive manner.
PMID- 28495310
TI - Resveratrol inhibits urban particulate matter-induced COX-2/PGE2 release in human
fibroblast-like synoviocytes via the inhibition of activation of NADPH
oxidase/ROS/NF-kappaB.
AB - Human fibroblast-like synoviocytes (FLSs) play a role in joint synovial
inflammation in rheumatoid arthritis (RA). Some evidence indicates that
particulate matter (PM) in air pollution could contribute to the progression of
RA. However, more research is needed to clarify this relationship. Up-regulation
of cyclooxygenase (COX)-2 and its metabolite prostaglandin E2 (PGE2) are
implicated in various inflammatory diseases. Resveratrol, a polyphenol found
mainly in grapes and red wine, has antioxidant and anti-inflammatory activities.
In the present study, we demonstrated that resveratrol reduced PM-induced COX
2/PGE2 expression in human FLSs, and attenuated PM-enhanced NADPH oxidase
activity and ROS generation. In addition, PM induced Akt, ERK1/2, or p38 MAPK
activation, which was inhibited by resveratrol. Finally, we demonstrated that PM
enhanced NF-kappaB p65 phosphorylation and the NF-kappaB promoter activity, which
were reduced by pretreatment with a ROS inhibitor or resveratrol. Thus, we
concluded that resveratrol functions as a suppressor of PM-induced inflammatory
signaling pathways by inhibiting COX-2/PGE2 expression.
PMID- 28495312
TI - Considerations of critical quality attributes in the analytical comparability
assessment of biosimilar products.
AB - Based on experience in clinical trial approvals and marketing authorizations for
biosimilar products in Korea, we suggest principles for the analytical
comparability assessment of biosimilar products with respect to regulatory
considerations. The composition and manufacturing processes of biosimilar
products can differ from those of the reference product depending on the
information available for the reference product and the time of product
development; however, the analytical characteristics of biosimilar products
should be highly similar to those of the reference product. Although
manufacturing an identical product in terms of the quality profile is nearly
impossible due to the high molecular weight and complex structure of biological
products, the developer of the biosimilar product should attempt to establish a
quality level as similar to that of the reference product as possible. When
comparing the similarity of quality attributes, the criticality of the quality
attributes and the characteristics of orthogonal quality attributes need to be
considered carefully. Based on the results from the analytical comparability
assessment, the comparability results of non-clinical and clinical studies should
be evaluated before claiming biosimilarity to the reference product. In this
review, we focus on quality attribute evaluation based on our regulatory
experience.
PMID- 28495311
TI - An Update on Memory Reconsolidation Updating.
AB - The reactivation of a stored memory in the brain can make the memory transiently
labile. During the time it takes for the memory to restabilize (reconsolidate)
the memory can either be reduced by an amnesic agent or enhanced by memory
enhancers. The change in memory expression is related to changes in the brain
correlates of long-term memory. Many have suggested that such retrieval-induced
plasticity is ideally placed to enable memories to be updated with new
information. This hypothesis has been tested experimentally, with a translational
perspective, by attempts to update maladaptive memories to reduce their
problematic impact. We review here progress on reconsolidation updating studies,
highlighting their translational exploitation and addressing recent challenges to
the reconsolidation field.
PMID- 28495313
TI - Posterior hypothalamus glutamate infusion decreases pentylenetetrazol-induced
seizures of male rats through hippocampal histamine increase.
AB - OBJECTIVES: Seizures are epileptic manifestations that are intrinsically
modulated through different neurotransmitters and receptor systems. Although
glutamate increases excitation and hence seizures, it activates other systems
which could potentially terminate seizures. Histamine originates from neurons of
the posterior hypothalamus (PH) and can mediate anticonvulsant properties, but
the effect of local PH glutamate on hippocampal histamine content is unknown.
Therefore, in this study, the effect of PH glutamate and the involvement of
hippocampal histamine in pentylenetetrazol (PTZ) induced seizure activity was
studied. MATERIALS AND METHODS: OX2R antagonist (TCS OX2 29, 40nmol/1MUl, intra
PH), AMPA/Kainate receptor antagonist (CNQX, 3mM, intra-PH) and glutamate (1mM)
were injected bilaterally into PH using stereotaxic surgery. The intravenous PTZ
infusion model was used to generate behavioral convulsions and the amount of
hippocampal histamine content was then measured using a biochemical method.
RESULTS: Administration of glutamate into PH decreased both seizure stage and the
duration of tonic-clonic convulsion (TCC) with increasing TCC latency and
hippocampal histamine content. Blocking OX2Rs alone or coinhibition of OX2Rs and
AMPA/kainate receptors reversed these effects by increasing both seizure stage
and TCC duration, and by decreasing both latency and consequent histamine
content. CONCLUSIONS: Our findings suggest that glutamate administration into PH
may control seizures (stages and duration) through increasing the hippocampal
histamine content.
PMID- 28495314
TI - A novel approach for construction of an inactivated typhoid vaccine candidate
that effectively augments both humoral and cellular immune responses.
AB - Salmonella enterica serovar Typhi ghost was constructed as a vaccine candidate
against typhoid fever. An asd+ plasmid pJHL187 harboring a ghost cassette
comprised of PhiX 174 E lysis gene stringently controlled under the convergent
promotor components and was transformed into the asd gene-deleted mutant S. Typhi
Ty21a strain (STG). Twenty female BALB/c mice randomly assigned into two groups
were subcutaneously vaccinated at 5weeks of age to assess immunogenic
characteristics of the constructed STG. The level of serum IgG in the immunized
mice was significantly increased during the observational period (P<0.001) as the
mice showed the significant elevation of secretory IgA at week 6 compared to
those in the non-immunized mice (P<0.05). The CD3+CD4+ T cell subpopulation in
the primed splenocytes showed approximately twofold increase in the immunized
group. Further, the gene expression of various immunomodulatory cytokines
associated with Th-1, Th-2 and Th-17 immunity was observed in in vitro
restimulated splenocytes isolated from the immunized mice. Serum Bactericidal
activity of antibodies produced in the rabbits immunized with STG was proved by
the elimination of almost all of wild-type S. Typhi in the presence of exogenous
complement over an hour at week 6 after the first immunization. The immuno
stimulatory traits of STG demonstrated that the construct effectively enhanced
the immunological responses, providing a potential of STG as the vaccine
candidate against typhoid fever.
PMID- 28495315
TI - Accelerated mass production of influenza virus seed stocks in HEK-293 suspension
cell cultures by reverse genetics.
AB - Despite major advances in developing capacities and alternative technologies to
egg-based production of influenza vaccines, responsiveness to an influenza
pandemic threat is limited by the time it takes to generate a Candidate Vaccine
Virus (CVV) as reported by the 2015 WHO Informal Consultation report titled
"Influenza Vaccine Response during the Start of a Pandemic". In previous work, we
have shown that HEK-293 cell culture in suspension and serum free medium is an
efficient production platform for cell culture manufacturing of influenza
candidate vaccines. This report, took advantage of, recombinant DNA technology
using Reverse Genetics of influenza strains, and advances in the large-scale
transfection of suspension cultured HEK-293 cells. We demonstrate the efficient
generation of H1N1 with the PR8 backbone reassortant under controlled bioreactor
conditions in two sequential steps (transfection/rescue and
infection/production). This approach could deliver a CVV for influenza vaccine
manufacturing within two-weeks, starting from HA and NA pandemic sequences.
Furthermore, the scalability of the transfection technology combined with the HEK
293 platform has been extensively demonstrated at >100L scale for several
biologics, including recombinant viruses. Thus, this innovative approach is
better suited to rationally engineer and mass produce influenza CVV within
significantly shorter timelines to enable an effective global response in
pandemic situations.
PMID- 28495316
TI - Effect of infectious bursal disease (IBD) vaccine on Salmonella Enteritidis
infected chickens.
AB - BACKGROUND: Chickens infected with both infectious bursal disease virus (IBDV)
and Salmonella had higher mortality. In this work, we investigated the effect of
IBDV vaccine (modified live-virus bursal disease vaccine, Nobilis strain 228E(r))
on experimentally infected chickens with Salmonella Enteritidis (SE). METHODS:
Four experimental groups were included in this study, negative control group,
228E(r)group, 228E(r)+SE infected group, and SE infected group. Chickens were
ocularly administrated 228E(r) at 12days of age and orally infected with S.
Enteritidis at 13days of age. Sera, intestinal fluid, blood, cloacal swabs and
tissue samples were collected at 1, 2 and 3weeks post vaccination (PV). RESULTS:
The recorded mortalities were higher in the 228E(r)+SE infected group, compared
to the SE infected group. The anti-S. Enteritidis serum antibody titer and the
intestinal mucosal IgA level were higher in the SE infected group at 2 and 3weeks
PV, compared to 228E(r)+SE infected group. S. Enteritidis fecal shedding and
organ colonization were significantly higher in the 228E(r)+SE infected group
than the SE infected group at 2 and 3weeks PV. The 228E(r)+SE group had
significantly lower bursa to body weight ratios at 2 and 3weeks PV, as well as
had higher bursal lesion scores than the SE infected group. IBDV vaccine
depressed the specific-SE systemic and mucosal antibody responses, but did not
affect the specific-SE cellular immune responses. CONCLUSION: Chickens
administrated IBDV vaccine, followed by S. Enteritidis infection, could cause a
significant effect on the bursa of Fabricius, resulting in failure of systemic
and mucosal antibody responses to the S. Enteritidis and reduce the elimination
and the clearance of S. Enteritidis.
PMID- 28495318
TI - The reno-cardiovascular connection in the patient with Diabetes mellitus: What's
new?
PMID- 28495317
TI - Cross-sectional study involving healthcare professionals in a Vaccinia virus
endemic area.
AB - Orthopoxviruses (OPV) are emerging viruses with great importance in human and
veterinary medicine, such as Vaccinia virus (VACV), which causes outbreaks of
bovine vaccinia (BV) in South America. The clinical aspects of BV are similar to
other vesicular infections, complicating the clinical diagnosis. This cross
sectional study evaluated the knowledge of Healthcare Professionals about BV and
revealed their unpreparedness about BV in a VACV hyper-endemic area in Brazil,
highlighting the public health issues associated with VACV infections. This study
presents an opportunity to discuss the importance of vaccination for healthcare
professionals who work in areas of VACV circulation and brings an educational
measure on VACV infections for health professionals around the world.
PMID- 28495319
TI - Clinical characteristics and mortality in patients treated in a Multidisciplinary
Diabetic Foot Unit.
AB - BACKGROUND AND OBJECTIVE: This study reviews the clinical characteristics of
patients with diabetic foot ulcer treated in a Multidisciplinary Diabetic Foot
Unit (MDFU) and analyzes the mortality and factors associated with its survival.
MATERIAL AND METHODS: Data from all patients who attended the MDFU for the first
time for a diabetic foot ulcer during the 2008-2014 period were analized. The
patients were followed until their death or until June 30, 2016, for up to 8
years. RESULTS: A total of 345 patients were included, with a median age (P25
P75) of 71 (61.5-80) years, and 321 (93%) had type 2 diabetes. They were
characterized as patients with inadequate glycemic control, 48% had HbA1c >= 8%
and high prevalence of chronic complications: 60.2% retinopathy, 43.8%
nephropathy and 47.2% ischemic heart disease and/or cerebrovascular disease. A
total of 126 (36.5%) patients died and 69 (54.8%) were due to cardiovascular
disease. Survival measured by Kaplan-Meier declined over time to 69, 60 and 45%
at 3, 5 and 7 years respectively. Cox's multivariate regression analysis showed
the following variables associated with mortality, HR (95% CI): age 1.08 (1.05
1.11); previous amputation 2.24 (1.34-3.73); active smoking 2.10 (1.12-3.97);
cerebrovascular disease 1.75 (1.05-2.92); renal dysfunction 1.65 (1.04-2.61) and
ischemic heart disease 1.60 (1.01-2.51). CONCLUSIONS: Patients with diabetic foot
ulcer are characterized by high morbidity and mortality, with cardiovascular
disease being the most frequent cause of death. It is necessary to pay more
attention to this risk group, tailoring objectives and treatments to their
situation and life expectancy.
PMID- 28495320
TI - Comparison of 2 intravenous insulin protocols: Glycemia variability in critically
ill patients.
AB - OBJECTIVE: Glycemic variability is an independent predictor of mortality in
critically ill patients. The objective of this study was to compare two
intravenous insulin protocols in critically ill patients regarding the glycemic
variability. MATERIAL AND METHODS: This was a retrospective observational study
performed by reviewing clinical records of patients from a Critical Care Unit for
4 consecutive months. First, a simpler Scale-Based Intravenous Insulin Protocol
(SBIIP) was reviewed and later it was compared for the same months of the
following year with a Sliding Scale-Based Intravenous Insulin Protocol (SSBIIP).
All adult patients admitted to the unit during the referred months were included.
Patients in whom the protocol was not adequately followed were excluded. A total
of 557 patients were reviewed, of whom they had needed intravenous insulin 73 in
the first group and 52 in the second group. Four and two patients were excluded
in each group respectively. RESULTS: Glycemic variability for both day 1 (DS1)
and total stay (DST) was lower in SSBIIP patients compared to SBIIP patients: SD1
34.88 vs 18.16 and SDT 36.45 vs 23.65 (P<.001). CONCLUSION: A glycemic management
protocol in critically ill patients based on sliding scales decreases glycemic
variability.
PMID- 28495321
TI - Increased salivary oxidative stress parameters in patients with type 2 diabetes:
Relation with periodontal disease.
AB - OBJECTIVE: The aim of this study was to determine whether there are differences
in salivary oxidative stress between patients with diabetes mellitus type 2 (DM2)
and healthy non-diabetic patients, and whether this oxidative stress is
associated with the presence of periodontal disease in diabetic patients.
MATERIAL AND METHODS: This observational study included 70 patients divided into
three groups according to metabolic control levels: 19 non-diabetic patients
(control group); 24 patients with good metabolic control (HbA1c<7%), and 27
patients DM2 with poor metabolic control (HbA1c>7%). The following oxidative
stress parameters were measured in all subjects: glutathione peroxidase (GPx),
glutathione reductase (GRd), reduced glutathione (GSH) and oxidized glutathione
(GSSG). Periodontal health was determined by means of the community periodontal
index (CPI) recommended by the WHO. RESULTS: The diabetic group with good
metabolic control showed a significant increase in GPx and GRd activity in
comparison with the control group (P<.001). The activity of the enzymes measured
was significantly less in patients with poor metabolic control in comparison with
the control group and well-controlled diabetic groups (P<.001). Both diabetic
groups showed higher GSSG/GSH quotients and CPI in comparison with the control
group, and both parameters were significantly higher in diabetic patients with
poor metabolic control in comparison with well-controlled diabetic patients.
CONCLUSIONS: Poor metabolic control in DM2 patients is associated with higher
levels of salivary oxidative stress and worse periodontal health.
PMID- 28495322
TI - Prevalence and control of type 2 diabetes mellitus among primary care physicians
in Spain. PRISMA Study.
AB - OBJECTIVE: To describe the prevalence of known and ignored type 2 diabetes
mellitus (T2DM) among primary care physicians (PCP), as well as the treatment
used and the degree of metabolic control reached. MATERIAL AND METHODS:
Descriptive cross-sectional study on national level. The participants were
randomly selected PCPs, members of the redGDPS Foundation. A total of 495 PCP
were enrolled. Capillary HbA1c measurement was done with a A1CNow+(r) device and
a diabetes-related survey specifically designed for the study was administered to
the participants. RESULTS: The total prevalence of T2DM was 11.1% (95% CI 8.33
13.9) (known disease 8,1% and ignored disease 3.0%). The prevalence of
prediabetes was 16.2% (95% CI 13.0-19.4). A total of 62.5% of PCPs with known
T2DM reached HbA1c<7% and 15% had HbA1c>8.5%. Control of blood pressure
(BP<140/90mmHg) was reached in 87.5% and control of LDL cholesterol<130mg/dl with
no history of cardiovascular disease was reached in 88.6% of cases of known T2DM.
In the PCPs with a history of macrovascular disease, good control of LDL was
reached in 42.9% of the cases. A total of 12.5% were active smokers. A total of
71.4% of PCPs with known T2DM self-treated their own disease, usually with 2 or
more drugs (51.4%). The most commonly used drug was metformin (74.3%) followed by
iDPP4 (48.6%). CONCLUSIONS: PCPs with T2DM have better metabolic control than the
general population. It is necessary to study whether PCPs with T2DM may have
greater adherence to treatment and do they achieve a better metabolic control.
PMID- 28495323
TI - Criteria for frusemide reduction or withdrawal.
PMID- 28495324
TI - Biology of the somatotroph axis (after the pituitary).
AB - Normal growth requires that pituitary-secreted growth hormone (GH) bind to its
specific receptor and activate a complex signaling cascade, leaving to production
of insulin-like growth factor-I (IGF-I), which, in turn, activates its own
receptor (IGF1R). The GH receptor (GHR) is preformed as a dimer and is
transported in a nonligand bound state to the cell surface. Binding of GH to the
GHR dimer, results in a conformational change of the dimer, activation of the
intracellular Janus Kinase 2 (JAK2) and phosphorylation of signal transducer and
activator of transcription (STAT) 5B. Phosphorylated STAT5B dimers are then
translocated to the nucleus, where they transcriptionally activate multiple
genes, including those for IGF-I, IGF binding protein-3 and the acid-labile
subunit (ALS).
PMID- 28495325
TI - Endocrine perturbations in POEMS syndrome: Misunderstood features of a rare
paraneoplastic syndrome.
PMID- 28495326
TI - Bone dysplasia.
AB - Bone dysplasia is a large group that encompasses 436 rare diseases. Many of them
are characterized by short stature or decreased growth velocity during puberty.
The diagnosis of short stature due to skeletal dysplasia relies on (i) physical
features such as disproportionate trunk/limbs, short limbs or extremities and/or
stocky build, (ii) radiographic features to analyze mineralization, maturation
and bone morphology, and (iii) whenever possible, the genetic characterization.
Bone dysplasia mostly affect many organs, and therefore require multidisciplinary
follow-up and care. The role of the pediatric endocrinologist is to assess the
growth potential of these patients in coordination with the other caregivers,
offer the best management of the growth to limit the psychosocial consequences of
the extreme short stature and bone deformities.
PMID- 28495327
TI - Vocal Change Patterns During a Teaching Day: Inter- and Intra-subject
Variability.
AB - OBJECTIVES: To describe the mean voice changes of 22 female teachers during a
typical workday, examine the inter- and intra-subject variability, and establish
a typology of different voice patterns during the workday. METHODS: For each
participant, fundamental frequency (F0), harmonics-to-noise ratio (HNR), jitter,
and shimmer were measured on sustained vowels at the beginning and at the end of
the workday, at three different times during the school year. RESULTS: The group
mean pattern showed significant increases in F0 and HNR during the workday and
significant decreases in jitter and shimmer. However, considerable inter- and
intra-subject variability was observed. Based on the variation in the acoustic
parameters during the workday, three different voice patterns were identified.
The first is characterized by a greater F0 increase during the day, interpreted
as a common, appropriate adaptation to vocal load. The second is characterized by
a greater increase in HNR during the day and greater decreases in jitter and
shimmer, interpreted as hyperfunctional voice production. The third is
characterized by greater decreases in F0 and HNR and greater increases in jitter
and shimmer, suggesting acute inflammation or muscle fatigue following the
workday. CONCLUSIONS: The observed variety of vocal patterns during the workday
emphasizes the need to study this phenomenon individually and target different
types of behaviors to develop tailored prevention and treatment methods.
PMID- 28495328
TI - Flow Glottogram and Subglottal Pressure Relationship in Singers and Untrained
Voices.
AB - This article combines results from three earlier investigations of the glottal
voice source during phonation at varying degrees of vocal loudness (1) in five
classically trained baritone singers (Sundberg et al., 1999), (2) in 15 female
and 14 male untrained voices (Sundberg et al., 2005), and (3) in voices rated as
hyperfunctional by an expert panel (Millgard et al., 2015). Voice source data
were obtained by inverse filtering. Associated subglottal pressures were
estimated from oral pressure during the occlusion for the consonant /p/. Five
flow glottogram parameters, (1) maximum flow declination rate (MFDR), (2) peak-to
peak pulse amplitude, (3) level difference between the first and the second
harmonics of the voice source, (4) closed quotient, and (5) normalized amplitude
quotient, were averaged across the singer subjects and related to associated MFDR
values. Strong, quantitative relations, expressed as equations, are found between
subglottal pressure and MFDR and between MFDR and each of the other flow
glottogram parameters. The values for the untrained voices, as well as those for
the voices rated as hyperfunctional, deviate systematically from the values
derived from the equations.
PMID- 28495329
TI - Dynamics of the Driving Force During the Normal Vocal Fold Vibration Cycle.
AB - Intraglottal pressure is the driving force of vocal fold vibration.
Theoretically, simultaneous quantification of glottal area and transglottal
airflow allows the calculation of the intraglottal pressure waveform during a
single vibration cycle. In this study, we show that, by combining
photoglottography (transglottal light transmission) and airflow (Rothenberg mask)
measurements during sustained vocal emissions in vivo, the intraglottal pressure
wave can be approximated in a way similar to what has been done in models. The
results confirm in vivo that the intraglottal pressure is systematically larger
during the opening phase than during the closing phase, so that over one whole
cycle, the driving force performs net positive work, accounting for sustained
vocal fold motion. A component of this driving force asymmetry is related to
vocal tract inertance, which also accounts for the skewing of the airflow
waveform compared with the area waveform. Furthermore, the intraglottal pressure
ratio (opening:closing) increases with voicing intensity, reaches a maximum
around 76 dB, and significantly decreases at higher intensities. This rise and
fall suggests that there is a range of intensity values in which, mechanically, a
maximum of the driving force is imparted to the vocal fold mass. This finding
could have implications for voice economy in professional speakers.
PMID- 28495330
TI - Relationships between age and microarchitectural descriptors of iliac trabecular
bone determined by microCT.
AB - AIM: Estimation of age at death is a major issue in anthropology. The main
anthropological histological methods propose studying the architecture of
cortical bone. In bone histomorphometry, researches on metabolic bone diseases
have provided normative tables for trabecular bone volume (BV/TV) according to
age and gender of individuals on trans-iliac bone biopsies. We have used microCT,
a non-destructive tool for measuring bone volume and trabecular descriptors to
compare the French tables to a series of forensic anthropological population and
if the two iliac bones could be used interchangeably. METHODOLOGY: Coxal bone of
a personal forensic collection whose age and gender were known (DNA
identification) were used. Bone samples, centered on the same area than bone
biopsy. MicroCT (pixel size: 36MUm) was used to measure BV/TV and morphometric
trabecular parameters of microarchitecture. An adjusted Z-score was calculated
for BV/TV to compare with normative tables and a right/left comparison of
trabecular parameters was provided. RESULTS: Twenty-seven iliac bones, which 20
forming 10 complete pelvises, aged between 24 and 73y.o. (average of 47.7 y.o.)
were used. All adjusted Z-score were within normal values. There was a strong
positive correlation between right and left sides for Tb.Th, Tb.N and Tb.Sp, but
an insignificant correlation was obtained for BV/TV. CONCLUSION: Normative tables
between age and BV/TV are valid and therefore usable in anthropology. They may
represent an alternative to determine the age at death. Nevertheless, it requires
a precise technique that could be a drawback in current practice.
PMID- 28495331
TI - Corrigendum to "Land use regression modelling of air pollution in high density
high rise cities: A case study in Hong Kong" [Sci. Total Environ. 592 (2017) 306
315].
PMID- 28495332
TI - The neural correlates of theory of mind and their role during empathy and the
game of chess: A functional magnetic resonance imaging study.
AB - Chess involves the capacity to reason iteratively about potential intentional
choices of an opponent and therefore involves high levels of explicit theory of
mind [ToM] (i.e. ability to infer mental states of others) alongside clear,
strategic rule-based decision-making. Functional magnetic resonance imaging was
used on 12 healthy male novice chess players to identify cortical regions
associated with chess, ToM and empathizing. The blood-oxygenation-level-dependent
(BOLD) response for chess and empathizing tasks was extracted from each ToM
region. Results showed neural overlap between ToM, chess and empathizing tasks in
right-hemisphere temporo-parietal junction (TPJ) [BA40], left-hemisphere superior
temporal gyrus [BA22] and posterior cingulate gyrus [BA23/31]. TPJ is suggested
to underlie the capacity to reason iteratively about another's internal state in
a range of tasks. Areas activated by ToM and empathy included right-hemisphere
orbitofrontal cortex and bilateral middle temporal gyrus: areas that become
active when there is need to inhibit one's own experience when considering the
internal state of another and for visual evaluation of action rationality.
Results support previous findings, that ToM recruits a neural network with each
region sub-serving a supporting role depending on the nature of the task itself.
In contrast, a network of cortical regions primarily located within right- and
left-hemisphere medial-frontal and parietal cortex, outside the internal
representational network, was selectively recruited during the chess task. We
hypothesize that in our cohort of novice chess players the strategy was to employ
an iterative thinking pattern which in part involved mentalizing processes and
recruited core ToM-related regions.
PMID- 28495333
TI - Sensory experience-dependent formation of perineuronal nets and expression of Cat
315 immunoreactive components in the mouse somatosensory cortex.
AB - Perineuronal nets (PNNs) are structures of extracellular matrix molecules
surrounding the cell bodies and proximal dendrites of certain neurons. While PNNs
are present throughout the mouse cerebral cortex, recent studies have shown that
the components differ among cortical sub-regions and layers, suggesting region
specific functions. Parvalbumin-expressing interneurons (PV neurons) may be
important regulators of cortical plasticity during the early "critical period"
that is sensitive to sensory input. Here we examined the distribution and
developmental functions of PNN components associated with PV neurons in the
somatosensory cortex during the critical period. Aggrecan, brevican, neurocan,
phosphacan, and tenascin-R were identified as PNN components in the mouse
somatosensory cortex. High-magnification analysis revealed that some lectin
Wisteria floribunda agglutinin (WFA)-reactive molecules did not co-localize with
monoclonal antibody Cat-315 recognition molecules around the cell body. During
postnatal development, Cat-315-positive (Cat-315+) PNNs appeared later than PNNs
binding to the lectin WFA (WFA+ PNNs). These WFA+ PNNs changed from granular-like
to reticular-like structures during normal cortical development, while this
transition was delayed by sensory deprivation. This study indicates that the
formation of reticular-like WFA+ PNNs is dependent on sensory experience in the
mouse somatosensory cortex. We suggest that Cat-315+ molecules and WFA expression
in PNNs are involved in the early critical period of input-dependent cortical
plasticity.
PMID- 28495334
TI - Found in Translation: Applying Lessons from Model Systems to Strigolactone
Signaling in Parasitic Plants.
AB - Strigolactones (SLs) are small molecules that act as endogenous hormones to
regulate plant development as well as exogenous cues that help parasitic plants
to infect their hosts. Given that parasitic plants are experimentally challenging
systems, researchers are using two approaches to understand how they respond to
host-derived SLs. The first involves extrapolating information on SLs from model
genetic systems to dissect their roles in parasitic plants. The second uses
chemicals to probe SL signaling directly in the parasite Striga hermonthica.
These approaches indicate that parasitic plants have co-opted a family of
alpha/beta hydrolases to perceive SLs. The importance of this genetic and
chemical information cannot be overstated since parasitic plant infestations are
major obstacles to food security in the developing world.
PMID- 28495335
TI - 50 years of prehospital resuscitation: Reflection and celebration.
PMID- 28495336
TI - The ability of older adults to use customized online medical databases to improve
their health-related knowledge.
AB - INTRODUCTION: Patient compliance with medical advice and recommended treatment
depends on perception of health condition, medical knowledge, attitude, and self
efficacy. This study investigated how use of customized online medical databases,
intended to improve knowledge in a variety of relevant medical topics, influenced
senior adults' perceptions. METHOD: Seventy-nine older adults in residence homes
completed a computerized, tablet-based questionnaire, with medical scenarios and
related questions. Following an intervention, control group participants answered
questions without online help while an experimental group received internet links
that directed them to customized, online medical databases. RESULTS: Medical
knowledge and test scores among the experimental group significantly improved
from pre- to post-intervention (p<0.0001) and was higher in comparison with the
control group (p<0.0001). No significant change occurred in the control group.
CONCLUSION: Older adults improved their knowledge in desired medical topic areas
using customized online medical databases. The study demonstrated how such
databases help solve health-related questions among older adult population
members, and that older patients appear willing to consider technology usage in
information acquisition.
PMID- 28495337
TI - Development and validation of detailed clinical models for nursing actions in
perinatal care.
AB - OBJECTIVES: The aim of this study was to develop and evaluate detailed clinical
models (DCMs) for nursing actions in perinatal care. We propose the use of action
target dyads as entities in DCMs for nursing actions. METHODS: We identified
action and target concepts, attributes, and value sets by analyzing nursing
documentation and reviewing the wider literature, in addition to published
standards and models. We developed the DCMs by linking entities, attributes, and
value sets. DCMs were classified by action type based on the Clinical Care
Classification, and by target type based on the axes of the International
Classification for Nursing Practice (ICNP). Attributes in the DCMs were also
classified by ICNP axes. The quality of the DCMs was evaluated by domain experts,
and their coverage was evaluated by mapping narrative nursing statements.
RESULTS: Nursing DCMs consisting of 233 entities (dyads comprising 34 action and
212 target concepts), 214 attributes and 541 values were developed. The most
frequent action type was hands-on care (43.3%). The focus axis was used most
frequently for the targets (51.9%) and attributes (38.8%). The quality scores of
the DCMs ranged from 0.80 to 0.96. Most (174/192; 90.6%) of the statements were
fully mapped, while 7 (3.7%) were partially mapped and 11 (5.7%) were not mapped.
We modified the DCMs in accordance with these results. CONCLUSIONS: In total, 240
DCMs were developed with action-target dyads as entities. The DCMs developed in
this study could be implemented in an electronic nursing record system to enhance
nursing practices and ensure semantic interoperability of nursing data.
PMID- 28495338
TI - Adoption of medication alert systems in hospital outpatient departments in
Taiwan.
AB - OBJECTIVE: The adoption of medication alert systems in the health care sector
varies among regions. In Taiwan, the health authority introduced policies in 2005
to encourage the adoption of medication alert systems in hospitals. This study
aimed to understand the adoption of medication alert systems in the outpatient
departments of hospitals in Taiwan using a nationwide survey. METHODS: A
questionnaire was developed and mailed to 380 accredited general hospitals in
Taiwan in 2013. The information collected from the questionnaire concerning the
outpatient department included (1) the time of adoption of a medication alert
system; (2) the operation of individual alert functions: availability,
management, and stability; and (3) hospital characteristics: accreditation level,
teaching status, ownership, and number of beds. RESULTS: A total of 216 hospitals
completed and returned the questionnaire, corresponding to a response rate of
56.8%. The adoption rate of medication alert systems in hospital outpatient
departments increased from less than 10% in 1997-95.83% in 2012. Approximately
two-thirds of the hospitals developed and maintained the alert systems
independently or collaboratively with vendors. Teaching and large hospitals
tended to develop more advanced alert functions such as drug-drug interaction
functions. Improving the safety and quality of pharmaceutical services and
meeting the policy requirements are reasons for hospitals to establish medication
alert systems. CONCLUSION: The adoption rate of medication alert systems reached
95% in accredited general hospitals in Taiwan. Government policy and available
health information professionals and vendors may somewhat contribute to the high
adoption rate.
PMID- 28495339
TI - User experience analysis of an eHealth system for tuberculosis in resource
constrained settings: A nine-country comparison.
AB - BACKGROUND: e-TB Manager, a web-based eHealth system has been successfully
institutionalized in 10 resource-constrained countries that account for one-third
of the world's tuberculosis (TB) burden, but user experience has never been
evaluated. METHODS: A cross-sectional, anonymous survey in eight unique languages
based on the targeted countries. e-TB Manager users included nurses, doctors,
pharmacists, statisticians/data officers, laboratory professionals/assistants,
health workers, and administrators. RESULTS: With an 86.3% completion rate for
all required questions, 1,511 completed responses were analyzed. Users had worked
in TB programs for a median of five years and had used e-TB Manager for a median
of two years. Overall, 60.2% of respondents were female, 65% were clustered in
the age groups of 30-39 and 40-49 years old, and nearly half (49%) were using e
TB Manager at the district and sub-district levels of a country's health system.
Older respondents aged over 50, regardless of location and with at least 6 or
more years of experience in public-sector TB programs, had higher mean
satisfaction scores than did their younger counterparts. Overall, those who had
used e-TB Manager for more than two years had significantly higher mean scores
for the majority of the survey statements than did those who had used e-TB
Manager for less than two years. Ukraine had significantly higher mean scores for
finding patient information available in e-TB Manager and in its benefit in
improving patient care compared to Brazil, Armenia, Nigeria, and Indonesia.
Brazil and Ukraine differed significantly from five other countries in that they
did not need additional training, thereby demonstrating their institutional
capacity after more than five years of using e-TB Manager. CONCLUSION: Although
users gave high ratings to e-TB Manager in terms of helping to improve patient
care, found it to be reliable, and were generally satisfied, there is need for a
combination of refresher training and e-learning methodologies to keep pace with
programmatic changes.
PMID- 28495340
TI - Investigating the determinants of Chinese adult children's intention to use
online health information for their aged parents.
AB - BACKGROUND: The increasing number of older people and the dissemination of health
information via the Internet have emerged and both are challenging to Chinese
society. Available online health information highlights the importance of
decision making processes, specially in relation to the elderly who almost have
no online presence and depend on their adult children's help. The researchers
mostly focus on parents' health information search for their children, however,
they overlook the adult children's intention to use online health information for
their aged parents. OBJECTIVE: This study fills this gap by extending the Theory
of Planned Behavior (TPB) to identify the determinants of adult children's
intention to use online health information for their aged parents. METHOD:
Relying on survey method, the data were collected from teachers and students at
different participating Universities in Wuhan, China. The Partial Least Squares
(PLS), a structural equation modeling technique, was employed to test the
research model. RESULTS: This study found that attitude, subjective norm,
perceived behavioral control and risk (p<0.05) were the predictors of intention
to use online health information, whereas, trust (p>0.05) was not listed among
the predictors. CONCLUSIONS: This study is a significant addition to the
literature, in that it confirms the utility of the TPB with additional variables
in predicting adults' children intention to use online health information for
their aged parents.
PMID- 28495341
TI - Estimation of the prevalence of adverse drug reactions from social media.
AB - This work aims to estimate the degree of adverse drug reactions (ADR) for
psychiatric medications from social media, including Twitter, Reddit, and
LiveJournal. Advances in lightning-fast cluster computing was employed to process
large scale data, consisting of 6.4 terabytes of data containing 3.8 billion
records from all the media. Rates of ADR were quantified using the SIDER database
of drugs and side-effects, and an estimated ADR rate was based on the prevalence
of discussion in the social media corpora. Agreement between these measures for a
sample of ten popular psychiatric drugs was evaluated using the Pearson
correlation coefficient, r, with values between 0.08 and 0.50. Word2vec, a novel
neural learning framework, was utilized to improve the coverage of variants of
ADR terms in the unstructured text by identifying syntactically or semantically
similar terms. Improved correlation coefficients, between 0.29 and 0.59,
demonstrates the capability of advanced techniques in machine learning to aid in
the discovery of meaningful patterns from medical data, and social media data, at
scale.
PMID- 28495342
TI - A method for cohort selection of cardiovascular disease records from an
electronic health record system.
AB - INTRODUCTION: An electronic healthcare record (EHR) system, when used by
healthcare providers, improves the quality of care for patients and helps to
lower costs. Information collected from manual or electronic health records can
also be used for purposes not directly related to patient care delivery, in which
case it is termed secondary use. EHR systems facilitate the collection of this
secondary use data, which can be used for research purposes like observational
studies, taking advantage of improvement in the structuring and retrieval of
patient information. However, some of the following problems are common when
conducting a research using this kind of data: (i) Over time, systems and data
storage methods become obsolete; (ii) Data concerns arise since the data is being
used in a context removed from its original intention; (iii) There are privacy
concerns when sharing data about individual subjects; (iv) The partial
availability of standard medical vocabularies and natural language processing
tools for non-English language limits information extraction from structured and
unstructured data in the EHR systems. A systematic approach is therefore needed
to overcome these, where local data processing is performed prior to data
sharing. METHOD: The proposed study describes a local processing method to
extract cohorts of patients for observational studies in four steps: (1) data
reorganization from an existing local logical schema into a common external
schema over which information can be extracted; (2) cleaning of data, generation
of the database profile and retrieval of indicators; (3) computation of derived
variables from original variables; (4) application of study design parameters to
transform longitudinal data into anonymized data sets ready for statistical
analysis and sharing. Mapping from the local logical schema into a common
external schema must be performed differently for each EHR and is not subject of
this work, but step 2, 3 and 4 are common to all EHRs. The external schema
accepts parameters that facilitate the extraction of different cohorts for
different studies without having to change the extraction algorithms, and ensures
that, given an immutable data set, can be done by the idempotent process.
Statistical analysis is part of the process to generate the results necessary for
inclusion in reports. The generation of indicators to describe the database
allows description of its characteristics, highlighting study results. The set
extraction/statistical processing is available in a version controlled repository
and can be used at any time to reproduce results, allowing the verification of
alterations and error corrections. This methodology promotes the development of
reproducible studies and allows potential research problems to be tracked upon
extraction algorithms and statistical methods RESULTS: This method was applied to
an admissions database, SI3, from the InCor-HCFMUSP, a tertiary referral hospital
for cardiovascular disease in the city of Sao Paulo, as a source of secondary
data with 1116848 patients records from 1999 up to 2013. The cleaning process
resulted in 313894 patients records and 27698 patients in the cohort selection,
with the following criteria: study period: 2003-2013, gender: Male, Female,
age:>=18years old, at least 2 outpatient encounters, diagnosis of cardiovascular
disease (ICD-10 codes: I20-I25, I64-I70 and G45). An R script provided
descriptive statistics of the extracted cohort. CONCLUSION: This method
guarantees a reproducible cohort extraction for use of secondary data in
observational studies with enough parameterization to support different study
designs and can be used on diverse data sources. Moreover it allows observational
electronic health record cohort research to be performed in a non-English
language with limited international recognized medical vocabulary.
PMID- 28495343
TI - Multimedia patient education to assist oral impression taking during dental
treatment: A pilot study.
AB - INTRODUCTION: Proper cooperation between patient and dentist is of great help to
make a good oral impression. However, patients are frequently confused when
information is given through traditional verbal description. The present study
compared the effectiveness of the multimedia information delivery ways with the
traditional verbal manner on patients' understanding level in oral impression
taking. METHODS: The recruited 191 participating patients were randomly assigned
to the control group (the verbal group) and two intervention groups (the video
group and the picture group) according to the information delivery manner. After
intervention, the patients' understanding degree was measured by questionnaire
and performance evaluation of behavior feedback on the provided information
quantitatively. Also, patients' self-assessment of satisfaction was interviewed
by telephone. All data was analyzed by SPSS 14.0 software, and p<=0.05 was set as
significant difference in advance. RESULTS: One-Way ANOVA and Chi-square showed
there were no statistically significant differences in the mean age, gender
composition, and educational level among the three groups (P>0.05). In both
questionnaire assessment and performance evaluation, One-Way ANOVA followed by
LSD indicate that the video group gained a higher score than the verbal group or
the picture group (P<0.05). The questionnaire score in the picture group is
significantly higher than in the control group (P<0.05), but no significant
difference was shown between these two groups in patients' performance evaluation
(P>0.05). Higher percentage of satisfaction was reported by patients in the two
multimedia groups than that in the control group. DISCUSSION: Oral impression
taking is a consecutive process that requires action cooperation between dentists
and patients simultaneously. This particularity makes it more suitable for
multimedia delivery. The delivery of tailored information using multimedia in
this study was favored by most patients and could improve the degree of patient
understanding of the oral impression taking procedures.
PMID- 28495344
TI - Does adoption of electronic health records improve the quality of care management
in France? Results from the French e-SI (PREPS-SIPS) study.
AB - BACKGROUND: Electronic health records (EHR) are increasingly being adopted by
healthcare systems worldwide. In France, the "Hopital numerique 2012-2017"
program was implemented as part of a strategic plan to modernize health
information technology (HIT), including the promotion of widespread EHR use. With
significant upfront investment costs as well as ongoing operational expenses, it
is important to assess this system in terms of its ability to result in
improvements in hospital performances. OBJECTIVE: The aim of this study was to
evaluate the impact of EHR use on the quality of care management in acute care
hospitals throughout France. METHODS: This retrospective study was based on data
derived from three national databases for the year 2011: IPAQSS (indicators of
improvement in the quality and the management of healthcare, "IPAQSS"), Hospi
Diag (French hospital performance indicators), and the national accreditation
database. Several multivariate models were used to examine the association
between the use of EHRs and specific EHR features with four quality indicators:
the quality of patient record, the delay in sending information at hospital
discharge, the pain status evaluation, and the nutritional status evaluation,
while also adjusting for hospital characteristics. RESULTS: The models revealed a
significant positive impact of EHR use on the four quality indicators.
Additionally, they showed a differential impact according to the functionality of
the element of the health record that was computerized. All four quality
indicators were also impacted by the type of hospital, the geographical region,
and the severity of the pathology. CONCLUSION: These results suggest that, to
improve the quality of care management in hospitals, EHR adoption represents an
important lever. They complete previous work dealing with EHR and the
organizational performance of hospital surgical units.
PMID- 28495345
TI - The Georges Pompidou University Hospital Clinical Data Warehouse: A 8-years
follow-up experience.
AB - BACKGROUND: When developed jointly with clinical information systems, clinical
data warehouses (CDWs) facilitate the reuse of healthcare data and leverage
clinical research. OBJECTIVE: To describe both data access and use for clinical
research, epidemiology and health service research of the "Hopital Europeen
Georges Pompidou" (HEGP) CDW. METHODS: The CDW has been developed since 2008
using an i2b2 platform. It was made available to health professionals and
researchers in October 2010. Procedures to access data have been implemented and
different access levels have been distinguished according to the nature of
queries. RESULTS: As of July 2016, the CDW contained the consolidated data of
over 860,000 patients followed since the opening of the HEGP hospital in July
2000. These data correspond to more than 122 million clinical item values, 124
million biological item values, and 3.7 million free text reports. The ethics
committee of the hospital evaluates all CDW projects that generate secondary data
marts. Characteristics of the 74 research projects validated between January 2011
and December 2015 are described. CONCLUSION: The use of HEGP CDWs is a key
facilitator for clinical research studies. It required however important
methodological and organizational support efforts from a biomedical informatics
department.
PMID- 28495346
TI - Changing the electronic request form proves to be an effective tool for
optimizing laboratory test utilization in the emergency department.
AB - OBJECTIVES: Appropriate laboratory utilization more often than not needs to be
initiated by the laboratory. This study was performed to analyze the impact on
test ordering patterns in the emergency department obtained by omitting certain
tests from the electronic tick box request form. The tests could still be ordered
by writing the full name of the test or by a phone call. METHODS: Erythrocyte
sedimentation rate (ESR), fibrinogen, aspartate aminotransferase (AST), calcium
and lipase were omitted from the electronic request form and could subsequently
be ordered either by phone or a typed-in request. A reflex testing protocol was
elaborated for reduction of creatine kinase (CK) and CK-MB analyses. All
interventions were introduced with prior consultation with clinical staff and
according to current guidelines. The reduction of test orders and costs in the
post-intervention period was assessed. All data were retrieved retrospectively
from the laboratory information system (LIS). RESULTS: Disappearance from the
tick box request form resulted in a significant decrease in the number of
requests for targeted tests in the post-intervention year, mostly affecting AST
and fibrinogen (83% and 79% reduction of ordering, respectively), followed by a
58% reduction in calcium orders, and 54% and 43% reductions in ESR and lipase
requests, respectively. A substantial reduction in CK requests was also observed,
while CK-MB requests almost disappeared. Annual cost savings that emerged from
all implemented interventions were estimated to be 19,445?. CONCLUSION:
Significant reduction in ordering of selected tests was achieved simply by
limiting their availability in hospital computerized order entry (COE) system.
The present data suggest that removal of laboratory tests from the electronic
request form can be an effective tool for changing physicians' test ordering
behavior.
PMID- 28495347
TI - A web-based clinical decision support system for gestational diabetes: Automatic
diet prescription and detection of insulin needs.
AB - BACKGROUND: The growth of diabetes prevalence is causing an increasing demand in
health care services which affects the clinicians' workload as medical resources
do not grow at the same rate as the diabetic population. Decision support tools
can help clinicians with the inspection of monitoring data, providing a
preliminary analysis to ease their interpretation and reduce the evaluation time
per patient. This paper presents Sinedie, a clinical decision support system
designed to manage the treatment of patients with gestational diabetes. Sinedie
aims to improve access to specialized healthcare assistance, to prevent patients
from unnecessary displacements, to reduce the evaluation time per patient and to
avoid gestational diabetes adverse outcomes. METHODS: A web-based telemedicine
platform was designed to remotely evaluate patients allowing them to upload their
glycaemia data at home directly from their glucose meter, as well as report other
monitoring variables like ketonuria and compliance to dietary treatment.
Glycaemia values, not tagged by patients, are automatically labelled with their
associated meal by a classifier based on the Expectation Maximization clustering
algorithm and a C4.5 decision tree learning algorithm. Two finite automata are
combined to determine the patient's metabolic condition, which is analysed by a
rule-based knowledge base to generate therapy adjustment recommendations. Diet
recommendations are automatically prescribed and notified to the patients,
whereas recommendations about insulin requirements are notified also to the
physicians, who will decide if insulin needs to be prescribed. The system
provides clinicians with a view where patients are prioritized according to their
metabolic condition. A randomized controlled clinical trial was designed to
evaluate the effectiveness and safety of Sinedie interventions versus standard
care and its impact in the professionals' workload in terms of the clinician's
time required per patient; number of face-to-face visits; frequency and duration
of telematics reviews; patients' compliance to self-monitoring; and patients'
satisfaction. RESULTS: Sinedie was clinically evaluated at "Parc Tauli University
Hospital" in Spain during 17 months with the participation of 90 patients with
gestational diabetes. Sinedie detected all situations that required a therapy
adjustment and all the generated recommendations were safe. The time devoted by
clinicians to patients' evaluation was reduced by 27.389% and face-to-face visits
per patient were reduced by 88.556%. Patients reported to be highly satisfied
with the system, considering it useful and trusting in being well controlled.
There was no monitoring loss and, in average, patients measured their glycaemia
3.890 times per day and sent their monitoring data every 3.477days. CONCLUSIONS:
Sinedie generates safe advice about therapy adjustments, reduces the clinicians'
workload and helps physicians to identify which patients need a more urgent or
more exhaustive examination and those who present good metabolic control.
Additionally, Sinedie saves patients unnecessary displacements which contributes
to medical centres' waiting list reduction.
PMID- 28495348
TI - Development of a tripolar model of technology acceptance: Hospital-based
physicians' perspective on EHR.
AB - BACKGROUND AND PURPOSE: In health care, information technologies (IT) hold a
promise to harness an ever-increasing flow of health related information and
bring significant benefits including improved quality of care, efficiency, and
cost containment. One of the main tools for collecting and utilizing health data
is the Electronic Health Record (EHR). EHRs implementation can face numerous
barriers to acceptance including attitudes and perceptions of potential users,
required effort attributed to their implementation and usage, and resistance to
change. Various theories explicate different aspects of technology deployment,
implementation, and acceptance. One of the common theories is the Technology
Acceptance Model (TAM), which helps to study the implementation of different
healthcare IT applications. The objectives of this study are: to understand the
barriers of EHR implementation from the perspective of physicians; to identify
major determinants of physicians' acceptance of technology; and develop a model
that explains better how EHRs (and technologies in general) are accepted by
physicians. METHODS: The proposed model derives from a cross-sectional survey of
physicians selected through multi-stage cluster sampling from the hospitals of
Yerevan, Armenia. The study team designed the survey instrument based on a
literature review on barriers of EHR implementation. The analysis employed
exploratory structural equation modeling (ESEM) with a robust weighted least
squares (WLSMV) estimator for categorical indicators. The analysis progressed in
two steps: appraisal of the measurement model and testing of the structural
model. RESULTS: The derived model identifies the following factors as direct
determinants of behavioral intention to use a novel technology: projected
collective usefulness; personal innovativeness; patient influence; and resistance
to change. Other factors (e.g., organizational change, professional
relationships, administrative monitoring, organizational support and computer
anxiety) exert their effects through projected collective usefulness, perceived
usefulness, and perceived ease of use. The model reconciles individual-oriented
and environment-oriented theoretical approaches and proposes a Tripolar Model of
Technology Acceptance (TMTA), bringing together three key pillars of the
healthcare: patients, practitioners, and provider organizations. The proposed
TMTA explains 85% of variance of behavioral intention to use technology.
CONCLUSIONS: The current study draws from the barriers of EHR implementation and
identifies major determinants of technology acceptance among physicians. The
study proposes TMTA as affording stronger explanative and predictive abilities
for the health care system. TMTA paves a long overlooked gap in TAM and its
descendants, which, in organizational settings, might distort construal of
technology acceptance. It also explicates with greater depth the interdependence
of different participants of the healthcare and complex interactions between
healthcare and technologies.
PMID- 28495349
TI - Factors that impact Patient Web Portal Readiness (PWPR) among the underserved.
AB - OBJECTIVE: Healthcare organizations in the US are increasingly using Patient
Portals as a means to provide patients with partial access to their health
records and thereby comply with the 'meaningful use' of Health Information
Technology policy issued by the US federal government. Patient portals are used
to not only provide access to parts of the health records such as lab results but
also offer services such as customized educational materials and appointment
scheduling. While prior studies examining the adoption rates of these patient
portals have not offered consistent findings, many of the studies have reported
limited adoption and use [1] of patient portals, especially among the underserved
population. This study explores the factors behind the reduced adoption rate of
patient portals among the underserved by focusing on their Patient Web Portal
Readiness (PWPR). DESIGN: The study empirically evaluates the impact of three
important variables on PWPR among the underserved: (a) Personal Health
Information Management (PHIM) activities, (b) patient attitude toward personal
health record keeping; and (c) use of Internet for health information seeking.
The study also incorporates three other factors: (d) access to Internet; (e)
demographics; and (f) presence of chronic illness. MEASUREMENTS: Data were
collected through a survey from 132 patients from the underserved population who
visited 5 free clinics in the Northern Virginia area in the US. The paper-based
survey was administered to the patients who visited these free clinics for care.
RESULTS: The study findings show support for the hypotheses related to the impact
of the two key factors - Personal Health Information Management (PHIM) activities
and attitude toward personal health record keeping - on PWPR. The findings also
indicate that the use of Internet for health information seeking has relatively
more impact than patient's Internet access on PWPR. Overall, the findings imply
the critical importance of complementary activities - e.g., PHIM activities,
Internet-based health information seeking - to enhance PWPR among the underserved
population.
PMID- 28495351
TI - Electronic health record in the internal medicine clinic of a Brazilian
university hospital: Expectations and satisfaction of physicians and patients.
AB - PURPOSE: To evaluate the satisfaction and expectations of patients and physicians
before and after the implementation of an electronic health record (EHR) in the
outpatient clinic of a university hospital. METHODS: We conducted 389 interviews
with patients and 151 with physicians before and after the implementation of a
commercial EHR at the internal medicine clinic of Hospital das Clinicas of the
Faculty of Medicine of the University of Sao Paulo (HC-FMUSP), Brazil. The
physicians were identified by their connection to the outpatient clinic and
categorized by their years since graduation: residents and preceptors (with 10
years or less of graduation) or assistants (with more than 10 years of
graduation). The answers to the questionnaire given by the physicians were
classified as favorable or against the use of EHR, before and after the
implementation of this system in this clinic, receiving 1 or 0 points,
respectively. The sum of these points generated a multiple regression score to
determine which factors contribute to the acceptance of EHR by physicians. We
also did a third survey, after the EHR was routinely established in the
outpatient clinic. RESULTS: The degree of patient satisfaction was the same
before and after implementation, with more than 90% positive evaluations. They
noted the use of the computer during the consultation and valued such use.
Resident (younger) physicians had more positive expectations than assistants
(older physicians) before EHR implementation. This optimism was reduced after
implementation. In the third evaluation the use of EHR was higher among resident
physicians. Resident physicians perceived and valued the EHR more and used it
more. In 28 of the 57 questions on performance of clinical tasks, resident
physicians found it easier to use EHR than assistant physicians with significant
differences (p<0.05). When questioned specifically about EHR satisfaction,
resident physicians responded "good" and "excellent" to a greater extent than
assistant physicians (p=0.002). CONCLUSIONS: Our results reinforce the idea that
the EHR introduction in a clinical setting should be preceded by careful planning
to improve physician's adherence to the use of EHR. Patients do not seem to
notice much difference to the quality of the consultation done using paper or
EHR. It became clear after the third evaluation with the physicians that the
younger (residents and some preceptors) perceived the advantages of the EHR more
than the older physicians. Resident physicians use the EHR more and are more
satisfied with it.
PMID- 28495350
TI - Decaying relevance of clinical data towards future decisions in data-driven
inpatient clinical order sets.
AB - OBJECTIVE: Determine how varying longitudinal historical training data can impact
prediction of future clinical decisions. Estimate the "decay rate" of clinical
data source relevance. MATERIALS AND METHODS: We trained a clinical order
recommender system, analogous to Netflix or Amazon's "Customers who bought A also
bought B..." product recommenders, based on a tertiary academic hospital's
structured electronic health record data. We used this system to predict future
(2013) admission orders based on different subsets of historical training data
(2009 through 2012), relative to existing human-authored order sets. RESULTS:
Predicting future (2013) inpatient orders is more accurate with models trained on
just one month of recent (2012) data than with 12 months of older (2009) data
(ROC AUC 0.91 vs. 0.88, precision 27% vs. 22%, recall 52% vs. 43%, all P<10-10).
Algorithmically learned models from even the older (2009) data was still more
effective than existing human-authored order sets (ROC AUC 0.81, precision 16%
recall 35%). Training with more longitudinal data (2009-2012) was no better than
using only the most recent (2012) data, unless applying a decaying weighting
scheme with a "half-life" of data relevance about 4 months. DISCUSSION: Clinical
practice patterns (automatically) learned from electronic health record data can
vary substantially across years. Gold standards for clinical decision support are
elusive moving targets, reinforcing the need for automated methods that can adapt
to evolving information. CONCLUSIONS AND RELEVANCM: Prioritizing small amounts of
recent data is more effective than using larger amounts of older data towards
future clinical predictions.
PMID- 28495352
TI - Reliability of commercially available sleep and activity trackers with manual
switch-to-sleep mode activation in free-living healthy individuals.
AB - INTRODUCTION: Wearable health devices have become trendy among consumers, but it
is not known whether they accurately measure sleep and physical activity
parameters. To address this question, we have studied the measured data of two
consumer-level activity monitors (Up Move Jawbone(r) (U) and Withings Pulse 02(r)
(W)) and compared it with reference methods for sleep and activity recordings,
namely the Bodymedia SenseWear Pro Armband(r) actigraph (SWA) and home
polysomnography (H-PSG). METHODS: Twenty healthy patients were assessed at home,
during sleep, with the four devices. An additional 24-h period of recording was
then planned during which they wore the 2 trackers and the SWA. Physical activity
and sleep parameters obtained with the 4 devices were analyzed. RESULTS:
Significant correlations with H-PSG were obtained for total sleep time (TST) for
all the devices: r=0.48 for W (p=0.04), r=0.63 for U (p=0.002), r=0.7 for SWA
(p=0.0003). The best coefficient was obtained with SWA. Significant correlations
were also obtained for time in bed (TIB) for U and SWA vs PSG (r=0.79 and r=0.76,
p<0.0001 for both) but not for W (r=0.45, p=0.07). No significant correlations
were obtained for deep sleep, light sleep, and sleep efficiency (SE) measurements
with W, U and SWA. Sleep latency (SL) correlated with H-PSG only when measured
against SWA (r=0.5, p=0.02). Physical activity assessment revealed significant
correlations for U and W with SWA for step count (both r=0.95 and p<0.0001) and
active energy expenditure (EE) (r=0.65 and 0.54; p=0.0006 and p<0.0001). Total EE
was also correctly estimated (r=0.75 and 0.52; p<0.0001 and p=0.001). CONCLUSION:
Sleep and activity monitors are only able to produce a limited set of reliable
measurements, such as TST, step count, and active EE, with a preference for U
which performs globally better. Despite the manual activation to sleep mode, U
and W were not suitable for giving correct data such as sleep architecture, SE,
and SL. In the future, to enhance accuracy of such monitors, researchers and
providers have to collaborate to write algorithms based reliably on sleep
physiology. It could avoid misleading the consumer.
PMID- 28495353
TI - Identifying patient-related information problems: A study of information use by
patient-care teams during morning rounds.
AB - OBJECTIVE: This study identifies the types of patient-related information
problems (PIPs) that patient-care teams encounter during morning rounds, and how
those PIPs are identified and managed. PIPs are any issues related to patient
information (e.g., wrong, missing, incomplete information) that affect the
patient-care team's ability to perform their work. Not addressing PIPs can lead
to workflow challenges, delayed patient-care decisions, and negative impacts to
the patient. MATERIALS AND METHODS: We employed qualitative data collection
methods by shadowing patient-care teams during 29 morning rounds resulting in
155h of observation. We observed the interactions between the rounding physicians
and other patient-care team members, including: nurses, consulting physicians,
care coordinators, pharmacists, social workers, and therapists. RESULTS: This
study resulted in identifying seven types of PIPs that occur during morning
rounds. Additionally, the study presents the different ways that participants
identified and managed the PIPs. DISCUSSION: We discuss the potential negative
effects of PIPs on the patient-care workflow. We also discuss socio-technical
recommendations for organizational policies and training, as well as electronic
health record (EHR) design improvements that could help patient-care teams more
effectively identify and manage PIPs. CONCLUSION: Hospital teams rely on
accurate, available, and up-to-date information in order to make informed
decisions on patient care. However, PIPs exist in EHR systems, paper documents,
and verbal conversations. This study identifies a set of PIPs and how they are
currently being identified and managed.
PMID- 28495354
TI - Tafenoquine for malaria prophylaxis in adults: An integrated safety analysis.
AB - BACKGROUND: Tafenoquine is a new prophylactic antimalarial drug. The current
analysis presents an integrated safety assessment of the Tafenoquine Anticipated
Clinical Regimen (Tafenoquine ACR) from 5 clinical trials, including 1 conducted
in deployed military personnel and 4 in non-deployed residents, which also
incorporated placebo and mefloquine comparator groups. METHODS: Adverse events
(AEs) were coded according to the Medical Dictionary for Regulatory Activities
(MedDRA(r), Version 15.0) and summarized. Among all subjects who had received the
Tafenoquine ACR, safety findings were compared for subjects who were deployed
military personnel from the Australian Defence Force (Deployed ADF) versus non
deployed residents (Resident Non-ADF). RESULTS: The incidence of at least one AE
was 80.6%, 64.1%, 67.6% and 94.9% in the mefloquine, placebo, tafenoquine
Resident Non-ADF and tafenoquine Deployed ADF groups, respectively. The latter
group had a higher incidence of AEs related to military deployment. AEs that
occurred at >= 1% incidence in both tafenoquine sub-groups and at a higher
frequency than placebo included diarrhea, nausea, vomiting, gastroenteritis,
nasopharyngeal tract infections, and back/neck pain. CONCLUSIONS: Weekly
administration of tafenoquine for up to six months increased the incidence of
gastrointestinal AEs, certain infections, and back/neck pain, but not the overall
incidence of AEs versus placebo. CLINICAL TRIAL REGISTRATION
NUMBERS/CLINICALTRIALS. GOV IDENTIFIERS: NCT02491606; NCT02488980; NCT02488902.
PMID- 28495355
TI - Tafenoquine is not neurotoxic following supertherapeutic dosing in rats.
AB - BACKGROUND: Tafenoquine is a new drug for malaria prevention. The goal of the
present work was to conduct a specific neurobehavioral study in rats with
histopathological assessment of the brain. METHODS: The clinical, hematological,
behavioral, motor activity, and neurohistopathologic changes induced by different
dose levels of tafenoquine were evaluated following single super-therapeutic dose
administration. Toxicokinetic data were generated to allow extrapolation to
clinical exposures. RESULTS: At the highest dose (500 mg/kg), two animals (of 12)
died. Surviving animals showed clinical signs of toxicity and had reduced body
weight 7-8 days after dosing. Decreases in motor activity were observed on more
than one occasion at doses > 9-fold higher than the clinical exposure. No
statistically significant changes were observed for other behavioral endpoints.
No neurohistopathological changes were noted. Changes in hematological and
clinical pathology endpoints were observed at the lowest dose level (125 mg/kg).
For context, the human dosing regimen is a 10 mg/kg load followed by 3.3 mg/kg
weekly (in a 60 kg person). CONCLUSIONS: As in humans, adverse events other than
neurotoxicity were dose-limiting for tafenoquine in rats. This raises the
prospect that a new weekly prophylactic, without neurologic liability, may become
available in the near future.
PMID- 28495356
TI - Scleral topography analysed by optical coherence tomography.
AB - PURPOSE: A detailed evaluation of the corneo-scleral-profile (CSP) is of
particular relevance in soft and scleral lenses fitting. The aim of this study
was to use optical coherence tomography (OCT) to analyse the profile of the
limbal sclera and to evaluate the relationship between central corneal radii,
corneal eccentricity and scleral radii. METHODS: Using OCT (Optos OCT/SLO;
Dunfermline, Scotland, UK) the limbal scleral radii (SR) of 30 subjects (11M,
19F; mean age 23.8+/-2.0SD years) were measured in eight meridians 45 degrees
apart. Central corneal radii (CR) and corneal eccentricity (CE) were evaluated
using the Oculus Keratograph 4 (Oculus, Wetzlar, Germany). Differences between SR
in the meridians and the associations between SR and corneal topography were
assessed. RESULTS: Median SR measured along 45 degrees (58.0; interquartile
range, 46.8-84.8mm) was significantly (p<0.001) flatter than along 0 degrees
(30.7; 24.5-44.3mm), 135 degrees (28.4; 24.9-30.9mm), 180 degrees (23.40; 21.3
25.4mm), 225 degrees (25.8; 22.4-32.4mm), 270 degrees (28.8; 25.3-33.1mm), 315
degrees (30.0; 25.0-36.9mm), and 90 degrees (37.1; 29.1-43.4mm). In addition,
the nasal SR along 0 degrees were significant flatter than the temporal SR along
180 degrees (p<0.001). Central corneal radius in the flat meridian (7.83+/
0.26mm) and in the steep meridian (7.65+/-0.26mm) did not correlate with SR
(p=0.186 to 0.998). There was no statistically significant correlation between
corneal eccentricity and scleral radii in each meridian (p=0.422). CONCLUSIONS:
With the OCT device used in this study it was possible to measure scleral radii
in eight different meridians. Scleral radii are independent of corneal topography
and may provide additional data useful in fitting soft and scleral contact
lenses.
PMID- 28495357
TI - European survey on forensic applications of massively parallel sequencing.
PMID- 28495359
TI - Gender differences in obstructive sleep apnoea, insomnia and restless legs
syndrome in adults - What do we know? A clinical update.
AB - Research in sleep medicine over the last decades has involved a broad variety of
sleep disorders in both men and women. Gender differences have been identified in
sleep physiology as well as in the three most common sleep disorders: obstructive
sleep apnoea (OSA), insomnia and restless legs syndrome (RLS). However, research
on gender differences in sleep medicine appears limited. This clinical review
aims to give an updated overview of gender differences, in relation to
prevalence, clinical presentation, treatment and quality of life in OSA, insomnia
and RLS. Future research directions in the adult population will also be
discussed.
PMID- 28495360
TI - Fractures and Osteomalacia in a Patient Treated With Frequent Home Hemodialysis.
AB - Bone deformities and fractures are common consequences of renal osteodystrophy in
the dialysis population. Persistent hypophosphatemia may be observed with more
frequent home hemodialysis regimens, but the specific effects on the skeleton are
unknown. We present a patient with end-stage renal disease treated with frequent
home hemodialysis who developed severe bone pain and multiple fractures,
including a hip fracture and a tibia-fibula fracture complicated by nonunion,
rendering her nonambulatory and wheelchair bound for more than a year. A bone
biopsy revealed severe osteomalacia, likely secondary to chronic hypophosphatemia
and hypocalcemia. Treatment changes included the addition of phosphate to the
dialysate, a higher dialysate calcium concentration, and increased calcitriol
dose. Several months later, the patient no longer required a wheelchair and was
able to ambulate without pain. Repeat bone biopsy revealed marked improvements in
bone mineralization and turnover parameters. Also, with increased dialysate
phosphate and calcium concentrations, as well as increased calcitriol,
circulating fibroblast growth factor 23 levels increased.
PMID- 28495358
TI - Animal to human translational paradigms relevant for approach avoidance conflict
decision making.
AB - Avoidance behavior in clinical anxiety disorders is often a decision made in
response to approach-avoidance conflict, resulting in a sacrifice of potential
rewards to avoid potential negative affective consequences. Animal research has a
long history of relying on paradigms related to approach-avoidance conflict to
model anxiety-relevant behavior. This approach includes punishment-based
conflict, exploratory, and social interaction tasks. There has been a recent
surge of interest in the translation of paradigms from animal to human, in
efforts to increase generalization of findings and support the development of
more effective mental health treatments. This article briefly reviews animal
tests related to approach-avoidance conflict and results from lesion and
pharmacologic studies utilizing these tests. We then provide a description of
translational human paradigms that have been developed to tap into related
constructs, summarizing behavioral and neuroimaging findings. Similarities and
differences in findings from analogous animal and human paradigms are discussed.
Lastly, we highlight opportunities for future research and paradigm development
that will support the clinical utility of this translational work.
PMID- 28495362
TI - Editorial Comment.
PMID- 28495361
TI - What lies in the near future for the treatment of rheumatoid arthritis?
PMID- 28495364
TI - Moxifloxacin is an effective and safe candidate agent for tuberculosis treatment:
a meta-analysis.
AB - BACKGROUND: To evaluate the efficacy and safety of the introduction of
moxifloxacin into the recommended regimen for tuberculosis (TB) treatment.
METHODS: A meta-analysis was performed of nine eligible studies regarding the
effect of moxifloxacin plus the recommended regimen compared to the recommended
regimen alone for the treatment of TB. RESULTS: In the efficacy analysis, the
overall odds ratio (OR) for sputum culture conversion was 1.895 (95% confidence
interval (CI) 1.355-2.651, p=0.000), indicating that when moxifloxacin is
combined with the recommended regimen, the rate of sputum culture conversion is
elevated compared to the recommended regimen alone. The overall OR for recurrence
was 0.516 (95% CI 0.342-0.920, p=0.022), suggesting that the introduction of
moxifloxacin into the recommended regimen reduces TB relapse after treatment. In
the safety analysis, the overall OR was estimated to be 1.001 (95% CI 0.855
1.172, p=0.989), demonstrating that adding moxifloxacin to the recommended
regimen does not cause more adverse events during TB treatment. CONCLUSIONS: This
meta-analysis suggests that the introduction of moxifloxacin into the recommended
regimen for the treatment of non-drug resistant TB improves the clinical outcome
by elevating the culture conversion rate and reducing the recurrence rate.
PMID- 28495363
TI - APP, APLP2 and LRP1 interact with PCSK9 but are not required for PCSK9-mediated
degradation of the LDLR in vivo.
AB - Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that
post-transcriptionally regulates the levels of hepatic low-density lipoprotein
receptors (LDLRs). PCSK9 binds to the extracellular domain of the LDLR, and the
PCSK9-LDLR complex is internalized through canonical clathrin-dependent
endocytosis and then delivered to lysosomes for degradation. The mechanism by
which PCSK9 blocks recycling of the LDLR has not been fully defined. Previous
reports showed that amyloid precursor-like protein 2 (APLP2) interacts with
PCSK9, but its role in PCSK9-mediated LDLR degradation remains controversial.
Here we found that amyloid precursor protein (APP), APLP2 and LDL receptor
related protein 1 (LRP1) interact with PCSK9. To test whether any of these
proteins are required for PCSK9-mediated LDLR degradation, we examined the
effects of disrupting these proteins in mice. Infusion of PCSK9 into App-/-,
Aplp2-/-, Aplp2-depleted App-/-, or liver-specific Lrp1-/- mice resulted in
similar reductions in the levels of hepatic LDLR as seen in wild-type (WT) mice.
Infusion of PCSK9 into WT mice also had no effect on the levels of hepatic APP,
APLP2 or LRP1. Thus, APP, APLP2 and LRP1 are not required for PCSK9-mediated LDLR
degradation and are not regulated by PCSK9 in vivo.
PMID- 28495365
TI - The yin and yang of apolipoprotein CIII.
PMID- 28495366
TI - Multimorbidity With HIV: Views of Community-Based People Living With HIV and
Other Chronic Conditions.
AB - People living with HIV (PLWH) experience an increase in chronic conditions with
aging, but little is known about experiences of living with multimorbidity with
HIV. Because early palliative care services may improve well-being for
individuals with multimorbidity, we planned to test an intervention to provide
these services to community-dwelling PLWH with other chronic conditions. To
tailor our intervention to the target population, we conducted four focus groups
(n = 22) that elicited health-related needs, experiences, and views regarding
palliative and other health services. We identified four themes related to
patients' needs and experiences: views of HIV as background to other chronic
conditions, challenges managing medications and provider interactions, concerns
about coping with future health needs, and persistence of HIV stigma. In
addressing multimorbidity with HIV, providers and patients may benefit from
enhanced attention to communication when crossing specialty areas and from
additional support to decrease stressors associated with HIV stigma.
PMID- 28495367
TI - In vivo effects of Allium cepa L. on the selected gut microflora and intestinal
histomorphology in broiler.
AB - The experiment was conducted to evaluate the effect of onion (Allium cepa L.,) on
the performance, gut microflora and intestinal histomorphology of broiler chicks.
Three hundred and twenty day old broiler chicks (Ross) were randomly divided into
four groups as A, B, C and D. Group A served as control without any
supplementation, group B, C and D was supplemented with onion powder at the rate
of 1.5, 2 and 2.5g/kg of feed respectively. Supplementation of onion
significantly (P<0.05) increased weight gain and feed consumption.
Supplementation of onion showed a significant (P<0.05) reduction in the
population of E. coli and increased significantly Lactobacillus and Streptococcus
species. Onion supplementation significantly (P<0.05) increased the morphometry
of length, width, crypt depth and surface area of the villus in duodenum, jejunum
and ileum of the small intestine. In conclusion, onion supplementation in broiler
produced a positive effect on performance, gut microflora and intestinal
histomorphology.
PMID- 28495368
TI - The dynamic programming high-order Dynamic Bayesian Networks learning for
identifying effective connectivity in human brain from fMRI.
AB - BACKGROUND: Determination of effective connectivity (EC) among brain regions
using fMRI is helpful in understanding the underlying neural mechanisms. Dynamic
Bayesian Networks (DBNs) are an appropriate class of probabilistic graphical
temporal-models that have been used in past to model EC from fMRI, specifically
order-one. NEW-METHOD: High-order DBNs (HO-DBNs) have still not been explored for
fMRI data. A fundamental problem faced in the structure-learning of HO-DBN is
high computational-burden and low accuracy by the existing heuristic search
techniques used for EC detection from fMRI. In this paper, we propose using
dynamic programming (DP) principle along with integration of properties of
scoring-function in a way to reduce search space for structure-learning of HO
DBNs and finally, for identifying EC from fMRI which has not been done yet to the
best of our knowledge. The proposed exact search-&-score learning approach HO-DBN
DP is an extension of the technique which was originally devised for learning a
BN's structure from static data (Singh and Moore, 2005). RESULTS: The
effectiveness in structure-learning is shown on synthetic fMRI dataset. The
algorithm reaches globally-optimal solution in appreciably reduced time
complexity than the static counterpart due to integration of properties. The
proof of optimality is provided. COMPARISON: The results demonstrate that HO-DBN
DP is comparably more accurate and faster than currently used structure-learning
algorithms used for identifying EC from fMRI. The real data EC from HO-DBN-DP
shows consistency with previous literature than the classical Granger Causality
method. CONCLUSION: Hence, the DP algorithm can be employed for reliable EC
estimates from experimental fMRI data.
PMID- 28495369
TI - Group-level spatio-temporal pattern recovery in MEG decoding using multi-task
joint feature learning.
AB - BACKGROUND: The use of machine learning models to discriminate between patterns
of neural activity has become in recent years a standard analysis approach in
neuroimaging studies. Whenever these models are linear, the estimated parameters
can be visualized in the form of brain maps which can aid in understanding how
brain activity in space and time underlies a cognitive function. However, the
recovered brain maps often suffer from lack of interpretability, especially in
group analysis of multi-subject data. NEW METHOD: To facilitate the application
of brain decoding in group-level analysis, we present an application of multi
task joint feature learning for group-level multivariate pattern recovery in
single-trial magnetoencephalography (MEG) decoding. The proposed method allows
for recovering sparse yet consistent patterns across different subjects, and
therefore enhances the interpretability of the decoding model. RESULTS: Our
experimental results demonstrate that the mutli-task joint feature learning
framework is capable of recovering more meaningful patterns of varying spatio
temporally distributed brain activity across individuals while still maintaining
excellent generalization performance. COMPARISON WITH EXISTING METHODS: We
compare the performance of the multi-task joint feature learning in terms of
generalization, reproducibility, and quality of pattern recovery against
traditional single-subject and pooling approaches on both simulated and real MEG
datasets. CONCLUSIONS: These results can facilitate the usage of brain decoding
for the characterization of fine-level distinctive patterns in group-level
inference. Considering the importance of group-level analysis, the proposed
approach can provide a methodological shift towards more interpretable brain
decoding models.
PMID- 28495371
TI - Detecting joint pausiness in parallel spike trains.
AB - BACKGROUND: Transient periods with reduced neuronal discharge - called 'pauses' -
have recently gained increasing attention. In dopamine neurons, pauses are
considered important teaching signals, encoding negative reward prediction
errors. Particularly simultaneous pauses are likely to have increased impact on
information processing. COMPARISON WITH EXISTING METHODS: Available methods for
detecting joint pausing analyze temporal overlap of pauses across spike trains.
Such techniques are threshold dependent and can fail to identify joint pauses
that are easily detectable by eye, particularly in spike trains with different
firing rates. NEW METHOD: We introduce a new statistic called pausiness that
measures the degree of synchronous pausing in spike train pairs and avoids
threshold-dependent identification of specific pauses. A new graphic termed the
cross-pauseogram compares the joint pausiness of two spike trains with its time
shifted analogue, such that a (pausiness) peak indicates joint pausing. When
assessing significance of pausiness peaks, we use a stochastic model with
synchronous spikes to disentangle joint pausiness arising from synchronous spikes
from additional 'joint excess pausiness' (JEP). Parameter estimates are obtained
from auto- and cross-correlograms, and statistical significance is assessed by
comparison to simulated cross-pauseograms. RESULTS: Our new method was applied to
dopamine neuron pairs recorded in the ventral tegmental area of awake behaving
mice. Significant JEP was detected in about 20% of the pairs. CONCLUSION: Given
the neurophysiological importance of pauses and the fact that neurons integrate
multiple inputs, our findings suggest that the analysis of JEP can reveal
interesting aspects in the activity of simultaneously recorded neurons.
PMID- 28495370
TI - An optimized method for enumerating CNS derived memory B cells during viral
induced inflammation.
AB - BACKGROUND: CNS inflammation resulting from infection, injury, or
neurodegeneration leads to accumulation of diverse B cell subsets. Although
antibody secreting cells (ASC) within the inflamed CNS have been extensively
examined, memory B cell (Bmem) characterization has been limited as they do not
secrete antibody without stimulation. Moreover, unlike human Bmem, reliable
surface markers for murine Bmem remain elusive. NEW METHOD: Using a viral
encephalomyelitis model we developed a modified limiting dilution in vitro
stimulation assay to convert CNS-derived virus specific Bmem into ASC. COMPARISON
WITH EXISTING METHODS: Stimulation methods established for lymphoid tissue cells
using prolonged stimulation with viral lysate resulted in substantial ASC loss
and minimal Bmem to ASC conversion of CNS-derived cells. By varying stimulation
duration, TLR activators, and culture supplements, we achieved optimal conversion
by culturing cells with TLR7/8 agonist R848 in the presence of feeder cells for
2days. RESULTS: Flow cytometry markers CD38 and CD73 characterizing murine Bmem
from lymphoid tissue showed more diverse expression patterns on corresponding CNS
derived B cell subsets. Using the optimized TLR7/8 stimulation protocol, we
compared virus-specific IgG Bmem versus pre-existing ASC within the brain and
spinal cord. Increasing Bmem frequencies during chronic infection mirrored
kinetics of ASC. However, despite initially similar Bmem and ASC accumulation,
Bmem prevailed in the brain, but were lower than ASC in the spinal cord during
persistence. CONCLUSION: Simultaneous enumeration of antigen-specific Bmem and
ASC using the Bmem assay optimized for CNS-derived cells enables characterization
of temporal changes during microbial or auto-antigen induced neuroinflammation.
PMID- 28495372
TI - Learning to recognize rat social behavior: Novel dataset and cross-dataset
application.
AB - BACKGROUND: Social behavior is an important aspect of rodent models. Automated
measuring tools that make use of video analysis and machine learning are an
increasingly attractive alternative to manual annotation. Because machine
learning-based methods need to be trained, it is important that they are
validated using data from different experiment settings. NEW METHOD: To develop
and validate automated measuring tools, there is a need for annotated rodent
interaction datasets. Currently, the availability of such datasets is limited to
two mouse datasets. We introduce the first, publicly available rat social
interaction dataset, RatSI. RESULTS: We demonstrate the practical value of the
novel dataset by using it as the training set for a rat interaction recognition
method. We show that behavior variations induced by the experiment setting can
lead to reduced performance, which illustrates the importance of cross-dataset
validation. Consequently, we add a simple adaptation step to our method and
improve the recognition performance. COMPARISON WITH EXISTING METHODS: Most
existing methods are trained and evaluated in one experimental setting, which
limits the predictive power of the evaluation to that particular setting. We
demonstrate that cross-dataset experiments provide more insight in the
performance of classifiers. CONCLUSIONS: With our novel, public dataset we
encourage the development and validation of automated recognition methods. We are
convinced that cross-dataset validation enhances our understanding of rodent
interactions and facilitates the development of more sophisticated recognition
methods. Combining them with adaptation techniques may enable us to apply
automated recognition methods to a variety of animals and experiment settings.
PMID- 28495373
TI - Amyloid-beta neurotoxicity and clearance are both regulated by glial group II
metabotropic glutamate receptors.
AB - Astrocytes are now fully endorsed as key players in CNS functionality and
plasticity. We recently showed that metabotropic glutamate receptor 3 (mGlu3R)
activation by LY379268 promotes non-amyloidogenic cleavage of amyloid precursor
protein (APP) in cultured astrocytes, leading to increased release of
neuroprotective sAPPalpha. Furthermore, mGlu3R expression is reduced in
hippocampal astrocytes from PDAPP-J20 mice, suggesting a role for these receptors
in Alzheimer's disease. The present study enquires into the role of astroglial
derived neurotrophins induced by mGlu3R activation in neurotoxicity triggered by
amyloid beta (Abeta). Conditioned medium from LY379268-treated astrocytes
protected hippocampal neurons from Abeta-induced cell death. Immunodepletion of
sAPPalpha from the conditioned medium prevented its protective effect. LY379268
induced brain-derived neurotrophic factor (BDNF) expression in astrocytes, and
neutralizing BDNF from conditioned medium also prevented its neuroprotective
effect on Abeta neurotoxicity. LY379268 was also able to decrease Abeta-induced
neuron death by acting directly on neuronal mGlu3R. On the other hand, LY379268
increased Abeta uptake in astrocytes and microglia. Indeed, and more importantly,
a reduction in Abeta-induced neuron death was observed when co-cultured with
LY379268-pretreated astrocytes, suggesting a link between neuroprotection and
increased glial phagocytic activity. Altogether, these results indicate a double
function for glial mGlu3R activation against Abeta neurotoxicity: (i) it
increases the release of protective neurotrophins such as sAPPalpha and BDNF, and
(ii) it induces amyloid removal from extracellular space by glia-mediated
phagocytosis.
PMID- 28495374
TI - Metyrapone prevents brain damage induced by status epilepticus in the rat lithium
pilocarpine model.
AB - The status epilepticus (SE) induced by lithium-pilocarpine is a well
characterized rodent model of the human temporal lobe epilepsy (TLE) which is
accompanied by severe brain damage. Stress and glucocorticoids markedly
contribute to exacerbate neuronal damage induced by seizures but the underlying
mechanisms are poorly understood. Herein we sought to investigate whether a
single administration of metyrapone (150 mg/kg, i.p.), an 11beta-hydroxylase
inhibitor, enzyme involved in the peripheral and central synthesis of
corticosteroids, had neuroprotective properties in this model. Two experiments
were carried out. In exp. 1, metyrapone was administered 3 h before pilocarpine
injection whereas in exp. 2, metyrapone administration took place at the onset of
the SE. In both experiments, 3 days after the insult, brain metabolism was
assessed by in vivo 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) positron emission
tomography (PET). Brains were processed for analyses of markers of hippocampal
integrity (Nissl staining), neurodegeneration (Fluoro-Jade C), astrogliosis
(glial fibrillary acidic protein (GFAP) immunohistochemistry) and, for a marker
of activated microglia by in vitro autoradiography with the TSPO (18 kDa
translocator protein) radioligand [18F]GE180. The SE resulted in a consistent
hypometabolism in hippocampus, cortex and striatum and neuronal damage,
hippocampal neurodegeneration, neuronal death and gliosis. Interestingly,
metyrapone had neuroprotective effects when administered before, but not after
the insult. In summary, we conclude that metyrapone administration prior but not
after the SE protected from brain damage induced by SE in the lithium-pilocarpine
model. Therefore, it seems that the effect of metyrapone is preventive in nature
and likely related to its antiseizure properties.
PMID- 28495375
TI - Methylene blue stimulates substrate-level phosphorylation catalysed by succinyl
CoA ligase in the citric acid cycle.
AB - Methylene blue (MB), a potential neuroprotective agent, is efficient in various
neurodegenerative disease models. Beneficial effects of MB have been attributed
to improvements in mitochondrial functions. Substrate-level phosphorylation (SLP)
results in the production of ATP independent from the ATP synthase (ATP-ase). In
energetically compromised mitochondria, ATP produced by SLP can prevent the
reversal of the adenine nucleotide translocase and thus the hydrolysis of
glycolytic ATP. The aim of the present study was to investigate the effect of MB
on mitochondrial SLP catalysed by succinyl-CoA ligase. Measurements were carried
out on isolated guinea pig cortical mitochondria respiring on alpha
ketoglutarate, glutamate, malate or succinate. The mitochondrial functions and
parameters like ATP synthesis, oxygen consumption, membrane potential, and
NAD(P)H level were followed online, in parallel with the redox state of MB. SLP
mediated ATP synthesis was measured in the presence of inhibitors for ATP-ase and
adenylate kinase. In the presence of the ATP-ase inhibitor oligomycin MB
stimulated respiration with all of the respiratory substrates. However, the rate
of ATP synthesis increased only with substrates alpha-ketoglutarate and glutamate
(forming succinyl-CoA). MB efficiently stimulated SLP and restored the membrane
potential in mitochondria also with the combined inhibition of Complex I and ATP
synthase. ATP formed by SLP alleviated the energetic insufficiency generated by
the lack of oxidative phosphorylation. Thus, the MB-mediated stimulation of SLP
might be important in maintaining the energetic competence of mitochondria and in
preventing the mitochondrial hydrolysis of glycolytic ATP. The mitochondrial
effects of MB are explained by the ability to accept electrons from reducing
equivalents and transfer them to cytochrome c bypassing the respiratory Complexes
I and III.
PMID- 28495376
TI - GABAA receptor positive allosteric modulators modify the abuse-related behavioral
and neurochemical effects of methamphetamine in rhesus monkeys.
AB - GABAA receptor positive allosteric modulators (GABAA receptor modulators) are
commonly used for the treatment of insomnia. Nevertheless, the effects of these
compounds on psychostimulant-induced sleep impairment are poorly understood.
Because GABAA receptor modulators have been shown to decrease the abuse-related
effects of psychostimulants, the aim of the present study was to evaluate the
effects of temazepam (0.3, 1.0 or 3.0 mg/kg) and eszopiclone (0.3, 1.0 or 3.0
mg/kg), two GABAA receptor modulators, on the behavioral neuropharmacology of
methamphetamine in adult rhesus macaques (n = 5). Sleep-like measures and general
daytime activity were evaluated with Actiwatch monitors. Methamphetamine self
administration (0.03 mg/kg/inf) was evaluated during morning sessions.
Methamphetamine-induced dopamine overflow was assessed through in vivo
microdialysis targeting the nucleus accumbens. Nighttime treatment with either
temazepam or eszopiclone was ineffective in improving sleep-like measures
disrupted by methamphetamine self-administration. Acute pretreatment with a low
dose of temazepam before self-administration sessions increased methamphetamine
self-administration without affecting normal daytime home-cage activity. At a
high dose, acute temazepam pretreatment decreased methamphetamine self
administration and attenuated methamphetamine-induced increases in dopamine in
the nucleus accumbens, without decreasing general daytime activity. Acute
eszopiclone treatment exerted no effects on methamphetamine intake or drug
induced increases in dopamine. Our study suggests that treatments based on GABAA
receptor modulators are not effective for the treatment of sleep disruption in
the context of psychostimulant use. In addition, distinct GABAA receptor
modulators differentially modulated the abuse-related effects of methamphetamine,
with acute treatment with the high efficacy GABAA receptor modulator temazepam
decreasing the behavioral and neurochemical effects of methamphetamine.
PMID- 28495377
TI - Assembling a supercapacitor electrode with dual metal oxides and activated carbon
using a liquid phase plasma.
AB - Developing supercapacitor electrodes at an affordable cost while improving their
energy and/or power density values is still a challenging task. This study
introduced a recipe which assembled a novel electrode composite using a liquid
phase plasma that was applied to a reactant solution containing an activated
carbon (AC) powder with dual metal precursors of iron and manganese. A comparison
was made between the composites doped with single and dual metal components as
well as among those synthesized under different precursor concentrations and
plasma durations. The results showed that increasing the precursor concentration
and plasma duration raised the content of both metal oxides in the composites,
whereas the deposition conditions were more favorable to iron oxide than
manganese oxide, due to its higher standard potential. The composite treated with
the longest plasma duration and highest manganese concentration was superior to
the others in terms of cyclic stability and equivalent series resistance. In
addition, the new composite selected out of them showed better electrochemical
performance than the raw AC material only and even two types of single metal
based composites, owing largely to the synergistic effect of the two metal
oxides. Therefore, the proposed methodology can be used to modify existing and
future composite electrodes to improve their performance with relatively cheap
host and guest materials.
PMID- 28495378
TI - Performance of biomorphic Silicon Carbide as particulate filter in diesel
boilers.
AB - Biomorphic Silicon Carbide (bioSiC) is a novel porous ceramic material with
excellent mechanical and thermal properties. Previous studies have demonstrated
that it may be a good candidate for its use as particle filter media of exhaust
gases at medium or high temperature. In order to determine the filtration
efficiency of biomorphic Silicon Carbide, and its adequacy as substrate for
diesel particulate filters, different bioSiC-samples have been tested in the flue
gases of a diesel boiler. For this purpose, an experimental facility to extract a
fraction of the boiler exhaust flow and filter it under controlled conditions has
been designed and built. Several filter samples with different microstructures,
obtained from different precursors, have been tested in this bench. The
experimental campaign was focused on the measurement of the number and size of
particles before and after placing the samples. Results show that the initial
efficiency of filters made from natural precursors is severely determined by the
cutting direction and associated microstructure. In biomorphic Silicon Carbide
derived from radially cut wood, the initial efficiency of the filter is higher
than 95%. Nevertheless, when the cut of the wood is axial, the efficiency depends
on the pore size and the permeability, reaching in some cases values in the range
70-90%. In this case, the presence of macropores in some of the samples reduces
their efficiency as particle traps. In continuous operation, the accumulation of
particles within the porous media leads to the formation of a soot cake, which
improves the efficiency except in the case when extra-large pores exist. For all
the samples, after a few operation cycles, capture efficiency was higher than
95%. These experimental results show the potential for developing filters for
diesel boilers based on biomorphic Silicon Carbide.
PMID- 28495379
TI - Transthoracic Echocardiography for Diagnosing Pulmonary Embolism: A Systematic
Review and Meta-Analysis.
AB - OBJECTIVE: Pulmonary embolism (PE) is a common diagnosis with significant
mortality if not appropriately treated. The use of transthoracic echocardiography
in patients with PE is common; however, its diagnostic capabilities in this use
are unclear. With the increased use of ultrasonography in medical settings, it is
important to understand the strengths and limitations of echocardiography for the
diagnosis of PE. METHODS: We conducted a systematic review of PubMed, CINAHL, and
EMBASE through 2016 for articles assessing the diagnostic accuracy of
transthoracic echocardiography for PE. Two authors independently abstracted
relevant data from the studies. We assessed quality using the QUADAS-2 tool for
diagnostic studies. RESULTS: Undefined "right heart strain" was the most common
sign used, and it had a sensitivity of 53% (95% CI, 45%-61%) and a specificity of
83% (95% CI, 74%-90%). Eleven other distinct signs were identified: ventricle
size ratio, abnormal septal motion, tricuspid regurgitation, 60/60 sign,
McConnell's sign, right heart thrombus, right ventricle hypokinesis, pulmonary
hypertension, right ventricular end-diastolic diameter, tricuspid annular plane
systolic excursion, and right ventricular systolic pressure. CONCLUSIONS: Studies
show a consistently high specificity and low sensitivity for echocardiography in
the diagnosis of PE, making it potentially adequate as a rule-in test at the
bedside in critical care settings such as the emergency department and intensive
care unit for patients with a suspicion of PE, especially those unable to get
other confirmatory studies. Future research may continue to clarify the role of
bedside echocardiography in conjunction with other tests and imaging in the
overall management of PE.
PMID- 28495380
TI - Outcomes associated with antibiotic regimens for treatment of Mycobacterium
abscessus in cystic fibrosis patients.
AB - BACKGROUND: Mycobacterium abscessus infection is associated with declining lung
function in cystic fibrosis (CF), but there is little evidence on clinical
efficacy to guide treatment. METHODS: Retrospective review of 37 CF patients
treated for M. abscessus respiratory infection at a single center from 2006 to
2014. Outcomes included change in FEV1 at 30, 60, 90, 180, and 365days after
treatment and clearance of M. abscessus from sputum cultures. RESULTS: Lung
function was significantly improved after 30 and 60days of treatment, but not at
later time points. Gains were inversely related to starting lung function.
Antibiotic choices did not influence outcomes except for greater clearance with
clarithromycin. CONCLUSIONS: Treatment of M. abscessus resulted in short term
improvement in lung function that is inversely related to pre-treatment FEV1.
PMID- 28495381
TI - A fragment-based approach leading to the discovery of a novel binding site and
the selective CK2 inhibitor CAM4066.
AB - Recently we reported the discovery of a potent and selective CK2alpha inhibitor
CAM4066. This compound inhibits CK2 activity by exploiting a pocket located
outside the ATP binding site (alphaD pocket). Here we describe in detail the
journey that led to the discovery of CAM4066 using the challenging fragment
linking strategy. Specifically, we aimed to develop inhibitors by linking a high
affinity fragment anchored in the alphaD site to a weakly binding warhead
fragment occupying the ATP site. Moreover, we describe the remarkable impact that
molecular modelling had on the development of this novel chemical tool. The work
described herein shows potential for the development of a novel class of CK2
inhibitors.
PMID- 28495382
TI - Synthesis and structure-activity relationship of teixobactin analogues via
convergent Ser ligation.
AB - Convergent Ser/Thr ligation has been used to prepare a series of teixobactin
analogues (28 in total) to establish a structure-activity relationship of
teixobactin. anti-bacterial evaluations of these synthetic analogues have
revealed the critical amino acid residues and the sites tolerable of
modifications. These studies will shed lights on the further development of
teixobactin analogues with improved antibacterial activities.
PMID- 28495383
TI - Zinc complex of tryptophan appended 1,4,7,10-tetraazacyclododecane as potential
anticancer agent: Synthesis and evaluation.
AB - With the rising incidences of cancer cases, the quest for new metal based
anticancer drugs has led to extensive research in cancer biology. Zinc complexes
of amino acid residue side chains are well recognized for hydrolysis of
phosphodiester bond in DNA at faster rate. In the presented work, a Zn(II)
complex of cyclen substituted with two l-tryptophan units, Zn(II)-Cyclen-(Trp)2
has been synthesized and evaluated for antiproliferative activity. Zn(II)-Cyclen
(Trp)2 was synthesized in ~70% yield and its DNA binding potential was evaluated
through QM/MM study which suggested good binding (G=-9.426) with B-DNA. The
decrease in intensity of the positive and negative bands of CT-DNA at 278nm and
240nm, respectively demonstrated an effective unwinding of the DNA helix with
loss of helicity. The complex was identified as an antiproliferative agent
against U-87MG cells with 5 fold increase in apoptosis with respect to control
(2h post incubation, IC50 25uM). Electrophoresis and comet assay studies
exhibited an increase in DNA breakage after treatment with complex while caspase
3/beta-actin cleavage established a caspase-3 dependent apoptosis pathway in U-87
MG cells after triggering DNA damage. In vivo tumor specificity of the developed
ligand was validated after radiocomplexation with 99mTc (>98% radiochemical yield
and specific activity of 2.56GBq/umol). Avid tumor/muscle ratio of >6 was
depicted in biodistribution and SPECT imaging studies in U-87 MG xenograft model
nude mice.
PMID- 28495384
TI - Medicinal chemistry of antischistosomal drugs: Praziquantel and oxamniquine.
AB - Neglected tropical diseases (NTDs) are a group of diseases that, besides
prevailing in poverty conditions, contribute to the maintenance of social
inequality, being a strong barrier to a country development. Schistosomiasis, a
NTD, is a tropical and subtropical disease caused by the trematode Schistosoma
mansoni (Africa, Middle East, Caribbean, Brazil, Venezuela, Suriname), japonicum
(China, Indonesia, the Philippines), mekongi (several districts of Cambodia and
the Lao People's Democratic Republic), intercalatum and guianensis (areas of
tropical rainforests in Central Africa) and hematobium (Middle East Africa,
Corsica, France) whose adult forms inhabit the mesenteric vessels of the host,
while the intermediate forms are found in the aquatic gastropod snails of the
genus Biomphalaria. Currently, praziquantel (PZQ) is the first line drug chosen
for the treatment of schistosomiasis according to the World Health Organization
(WHO) Model List of Essential Medicines, 2015. PZQ chemotherapy is considered to
be the most important development for decades in the treatment of
schistosomiasis. Beside the PZQ, oxamniquine (OXA) has been first described in
1969 and launched in Brazil by Pfizer under the name of Mansil(r) for oral
administration. It has a lower cost when compared to PZQ, being active in the
intestinal and hepatosplenic infections caused exclusively by S. mansoni, single
species in Brazil. Both PZQ and OXA have limitations, as low efficacy in the
treatment of acute schistosomiasis, low activity against S. mansoni in immature
stages and resistance or tolerance, which is the reason why further research are
still necessary for the development of a second generation of antischistosomal
drugs. For the development of new PZQ analogs, three main strategies can be
adopted: (a) synthesis and evaluation of PZQ analogues; (b) rational design of
new pharmacophores; (c) discovery of new active compounds from screening programs
on a large scale. Such (b) approach is difficult as the target of PZQ still
unknown, the synthesis of new active analogues is possible from delineation of
structure-activity relationships for PZQ. Thus, we proposed for a review article
an accurate analysis of PZQ and OXA medicinal properties and uses, focusing on
the pharmacochemical aspects of both drugs through 178 bibliographic references.
The mechanisms of action will be discussed, with the latest information available
in the literature (for the first time in the case of the oxamniquine). Cases of
resistance are also discussed. As both drugs are available as a racemic mixture
the biological impact of their stereochemistry to activity and side effects are
reviewed. The results obtained for the combination of PZQ and artemisinin
derivatives against immature worms are also introduced in the discussion. Using
the information about more than 200 PZQ new derivatives synthetized during almost
35years since its discovery, a deep structure-activity relationship (SAR) is also
proposed in this study.
PMID- 28495385
TI - Derivatives of caffeic acid, a natural antioxidant, as the basis for the
discovery of novel nonpeptidic neurotrophic agents.
AB - Neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease,
threaten the lives of millions of people and the number of affected patients is
constantly growing with the increase of the aging population. Small molecule
neurotrophic agents represent promising therapeutics for the pharmacological
management of neurodegenerative diseases. In this study, a series of caffeic acid
amide analogues with variable alkyl chain lengths, including ACAF3 (C3), ACAF4
(C4), ACAF6 (C6), ACAF8 (C8) and ACAF12 (C12) were synthesized and their
neurotrophic activity was examined by different methods in PC12 neuronal cells.
We found that all caffeic acid amide derivatives significantly increased survival
in PC12 neuronal cells in serum-deprived conditions at 25MUM, as measured by the
MTT assay. ACAF4, ACAF6 and ACAF8 at 5uM also significantly enhanced the effect
of nerve growth factor (NGF) in inducing neurite outgrowth, a sign of neuronal
differentiation. The neurotrophic effects of amide derivatives did not seem to be
mediated by direct activation of tropomyosin receptor kinase A (TrkA) receptor,
since K252a, a potent TrkA antagonist, did not block the neuronal survival
enhancement effect. Similarly, the active compounds did not activate TrkA as
measured by immunoblotting with anti-phosphoTrkA antibody. We also examined the
effect of amide derivatives on signaling pathways involved in survival and
differentiation by immunoblotting. ACAF4 and ACAF12 induced ERK1/2
phosphorylation in PC12 cells at 5 and 25uM, while ACAF12 was also able to
significantly increase AKT phosphorylation at 5 and 25uM. Molecular docking
studies indicated that compared to the parental compound caffeic acid, ACAF12
exhibited higher binding energy with phosphoinositide 3-kinase (PI3K) as a
putative molecular target. Based on Lipinski's rule of five, all of the compounds
obeyed three molecular descriptors (HBD, HBA and MM) in drug-likeness test. Taken
together, these findings show for the first time that caffeic amides possess
strong neurotrophic effects exerted via modulation of ERK1/2 and AKT signaling
pathways presumably by activation of PI3K and thus represent promising agents for
the discovery of neurotrophic compounds for management of neurodegenerative
diseases.
PMID- 28495386
TI - Development of molecular tools based on the dopamine D3 receptor ligand FAUC 329
showing inhibiting effects on drug and food maintained behavior.
AB - Dopamine D3 receptor-mediated networks have been associated with a wide range of
neuropsychiatric diseases, drug addiction and food maintained behavior, which
makes D3 a highly promising biological target. The previously described dopamine
D3 receptor ligand FAUC 329 (1) showed protective effects against dopamine
depletion in a MPTP mouse model of Parkinson's disease. We used the radioligand
[18F]2, a [18F]fluoroethoxy substituted analog of the lead compound 1 as a
molecular tool for visualization of D3-rich brain regions including the islands
of Calleja. Furthermore, structural modifications are reported leading to the
pyrimidylpiperazine derivatives 3 and 9 displaying superior subtype selectivity
and preference over serotonergic receptors. Evaluation of the lead compound 1 on
cocaine-seeking behavior in non-human primates showed a substantial reduction in
cocaine self-administration behavior and food intake.
PMID- 28495387
TI - Meta-analysis of serum non-high-density lipoprotein cholesterol and risk of
coronary heart disease in the general population.
AB - BACKGROUND: Non-high-density lipoprotein cholesterol (non-HDL-C) has been
proposed an independent risk factor for coronary heart disease (CHD). However,
the magnitude of this association in the general population varied considerably.
OBJECTIVE: To investigate the association of baseline non-HDL-C level with CHD
risk in the general population by conducting a meta-analysis. METHODS: A
comprehensive literature search was performed in the Pubmed and Embase until
January 2017. Prospective observational studies that investigated the association
between baseline non-HDL-C level and CHD risk in the general population were
included. Pooled hazard ratio (HR) and corresponding 95% confidence interval (CI)
were calculated for the highest vs. the lowest non-HDL-C category. RESULTS: Seven
articles with 9 independent prospective studies involving 448,732 individuals
were included. Meta-analysis showed that individuals with the highest non-HDL-C
level at baseline were associated with greater risk of CHD (RR 1.79; 95% CI 1.68
1.91) than those in the lowest non-HDL-C level category. Subgroup analysis
suggested that the risk of CHD seemed more pronounced among men (HR 1.98; 95% CI
1.70-2.30) than among women (HR 1.63; 95% CI 1.35-1.96). CONCLUSIONS: Higher
baseline non-HDL-C level is associated with increased risk of CHD in the general
population. This risk seems more pronounced in men than in women. However, gender
difference in non-HDL-C level associated with CHD risk should be verified by more
well-designed prospective studies.
PMID- 28495388
TI - Recognizing and differentiating uncommon body fluids: Considerations and tools
for a proper practical approach.
AB - Clinical laboratories are regularly requested to inspect uncommon body fluids
obtained from patients because clinicians are uncertain as to the origin of the
collected material. They may need this information for the actual diagnosis, to
confirm a supposition, or for guiding treatment and invasive operations like
draining and puncturing. Often there is also a need to know more precisely what
is going on in the cavity that gave rise to the fluid, for instance a local
infection or metastasis, or whether the cavity is connected to organs or fluid
compartments nearby etcetera. The results of the laboratory investigations often
have () direct consequences. As the investigation of uncommon body fluids is
distinct from routine laboratory analyses it requires special attention. This
paper presents an overview of the characteristics of uncommon human body fluids,
constituents useful as markers for recognizing and differentiating fluids and
considerations that have to be taken into account when interpreting the results
of analyses. In addition a number of practical recommendations for approaching
the task of identifying uncommon body fluids are given.
PMID- 28495389
TI - Clinical trainees' responses to parents who question evidence-based
recommendations.
AB - OBJECTIVE: We examined clinicians' attitudes, beliefs, and behavioral intentions
about discussing evidence and eliciting values when patients question
recommendations. METHODS: We randomized trainees to read one of three scenarios
about a parent of a one-year-old: 1) overuse (parent requests antibiotics for
presumed viral infection); 2) equipoise (tubes for recurrent ear infections); 3)
underuse (parent hesitates about vaccination). Participants then answered survey
questions. Outcomes included time spent clarifying values (primary), attitudes
and beliefs about the parent (secondary). RESULTS: 132 medical students and
pediatric residents enrolled; 119 (90%) completed the study. There were no
differences in time participants would spend clarifying values (antibiotics 26+/
12%; equipoise 28+/-11%; vaccine-hesitancy 22+/-11%; p=0.058). Participants in
the vaccine-hesitancy group (vs. other groups) would spend less time answering
questions (p=0.006). Participants in the antibiotics (vs. equipoise) group
perceived the parent as difficult (p=0.0002). Those in the vaccine-hesitancy
group (vs. other groups) perceived the parent as difficult, saw less value in the
conversation, and had lower respect for the parent's views (all ps<0.0001). Most
(76%) wanted additional training navigating these discussions. CONCLUSION:
Clinicians' attitudes may impact conversations when patients question evidence
based recommendations. PRACTICE IMPLICATIONS: Clinicians should consider ways to
discuss evidence and clarify patients' values to optimize health without damaging
patient-clinician relationships.
PMID- 28495390
TI - Interaction-A missing piece of the jigsaw in interpreter-mediated medical
consultation models.
AB - In 2015, at the International Conference on Communication in Healthcare in New
Orleans, USA, we formed a symposium panel to discuss and debate how
interdisciplinary research can inform interpreter-mediated medical consultation
training. In all our work, a recurring theme is not just the strengths but also
the shortcomings of the guidelines proposed in the textbooks and widely used in
medical education. This paper is an account of our multidisciplinary reflections
on a prominent issue of the lack of attention to interaction in communications,
which shed light on the limitations of these guidelines and clinical
communication models. We propose that an international network be established for
all stakeholders to foster interprofessional and interdisciplinary collaboration
for research and clinical interventions, and to inform training and policy
making.
PMID- 28495392
TI - Elderly polypharmacy patients' needs and concerns regarding medication assessed
using the structured patient-pharmacist consultation model.
AB - OBJECTIVE: To evaluate elderly polypharmacy patients' needs and concerns
regarding medication through the Structured Patient-Pharmacist Consultation
(SPPC). METHODS: Older patients on chronic treatment with >=5 medications were
asked to fill in the SPPC form at home. A consultation with the community
pharmacist, structured according to patient's answers, followed within 2-4 weeks.
Logistic regression associated patients' individual treatment with care issues
and consultation outcomes. RESULTS: Out of 440 patients, 39.5% experienced
problems, and 46.1% had concerns about medication use. 122 patients reported
reasons for discontinuing treatment. The main outcome of the consultation was a
better understanding of medication use (75.5%). Side effects and/or non-adherence
were identified in 50% of patients, and 26.6% were referred to the doctor. Atrial
fibrillation, COPD, anticoagulants, benzodiazepines, and beta
agonists/corticosteroids were associated with problems during medication use.
Patients with diabetes improved their understanding of medication use
significantly. CONCLUSION: Patients on benzodiazepines, anticoagulants, and beta
agonists/corticosteroids, with atrial fibrillation and/or COPD, may have a higher
potential for non-adherence. Counseling patients based on the SPPC model may be
particularly useful for patients with diabetes. PRACTICE IMPLICATIONS: The SPPC
model is a useful tool for counseling based on patient needs.
PMID- 28495391
TI - Engaging women with an embodied conversational agent to deliver mindfulness and
lifestyle recommendations: A feasibility randomized control trial.
AB - OBJECTIVE: This randomized controlled trial evaluates the feasibility of using an
Embodied Conversational Agent (ECA) to teach lifestyle modifications to urban
women. METHODS: Women were randomized to either 1) an ECA (content included:
mindfulness, stress management, physical activity, and healthy eating) or 2)
patient education sheets mirroring same content plus a meditation CD/MP3 once a
day for one month. General outcome measures included: number of stress management
techniques used, physical activity levels, and eating patterns. RESULTS: Sixty
one women ages 18 to 50 were enrolled. On average, 51% identified as white, 26%
as black, 23% as other races; and 20% as Hispanic. The major stress management
techniques reported at baseline were: exercise (69%), listening to music (70%),
and social support (66%). After one month, women randomized to the ECA
significantly decreased alcohol consumption to reduce stress (p=0.03) and
increased daily fruit consumption by an average of 2 servings compared to the
control (p=0.04). CONCLUSION: It is feasible to use an ECA to promote health
behaviors on stress management and healthy eating among diverse urban women.
PRACTICE IMPLICATIONS: Compared to patient information sheets, ECAs provide
promise as a way to teach healthy lifestyle behaviors to diverse urban women.
PMID- 28495393
TI - Correction of chin ptosis.
AB - Chin ptosis is described as a descent of the soft tissue from the symphyseal
region to a position under the lower contour of the mandible. Given its
multifactorial causes, treatment must be determined on a patient-by-patient
basis. While augmentation of the submental crease is a versatile option for the
correction of chin ptosis, this only corrects the soft tissue component. A
technical modification to treat dynamic chin ptosis, associated with bone
reduction in the mandibular symphysis, is presented here.
PMID- 28495394
TI - Chronic temporomandibular joint pain: two cases of osteoid osteoma and a review
of the literature.
AB - Osteoid osteoma is a benign bone tumour with self-limiting growth potential
occurring in any part of the body. Two rare cases of a pathologically proven
osteoid osteoma invading the temporomandibular joint (TMJ) are reported herein.
This article also reviews the cases of osteoid osteoma of the craniofacial
complex reported in the English-language literature to date. Although the
clinical presentation of osteoid osteoma in the jaw differs from that of osteoid
osteoma in the more common locations, the radiographic features are similar. In
both cases presented, computed tomography revealed a small round osseous lesion
with sharp margins in the TMJ. Bone scintigraphy was performed in order to
differentiate the lesions from other osseous lesions. Both patients underwent
surgical excision of the lesion with immediate relief of the pain. The importance
of early recognition of the clinical and imaging characteristics of an osteoid
osteoma of the TMJ is emphasized, in order to prevent misdiagnosis and avoid
discouraging therapies.
PMID- 28495395
TI - Study of the variables associated with local complement activation in IgA
nephropathy.
AB - OBJECTIVES: 1. To identify the variables that are associated with urinary levels
of properdin, MBL, C4d, and C5b-9 in patients with idiopathic IgA nephropathy. 2.
To analyse whether urinary levels of MBL and/or C4d are useful for identifying
the presence of mesangial deposits of C4d/MBL. PATIENTS AND METHOD: A total of 96
patients with IgA nephropathy were studied. Demographic, clinical and biochemical
variables were recorded at the time of diagnosis. Renal lesions were quantified
using the Oxford classification. Immunohistochemical staining for MBL, MASP-2,
properdin, C4d, and C5b-9 was performed in kidney biopsies, and in urine, the
levels of properdin, MBL, C4d and C5b-9 were determined. RESULTS: In multivariate
analysis, the independent predictors of C4d and MBL levels in urine were the
mesangial deposits of each protein and, to a lesser extent, the urinary protein
excretion. The independent predictors of urinary levels of C5b-9 were MBL
properdin and proteinuria. Urinary excretion of C4d had a sensitivity of 90% (95%
CI: 58,7 to 99) and a specificity of 73% (95% CI: 54-87) for detecting mesangial
C4d deposits, and the level of MBL had a sensitivity of 83.9% (95% CI: 62-95) and
a specificity of 81.6% (95% CI: 65-92) for identifying mesangial deposits of MBL.
CONCLUSION: The main predictor of urinary concentration of C4d and MBL was the
presence of their respective mesangial deposits. Urine MBL may contribute to
complement activation in the tubular luz through the lectin pathway. Urinary
levels of MBL and C4d could be sensitive and specific biomarkers for the
identification of patients with mesangial deposits of MBL and C4d.
PMID- 28495396
TI - Cardiovascular risk prediction in chronic kidney disease patients.
AB - INTRODUCTION: Scores underestimate the prediction of cardiovascular risk (CVR) as
they are not validated in patients with chronic kidney disease (CKD). Two of the
most commonly used scores are the Framingham Risk Score (FRS-CVD) and the ASCVD
(AHA/ACC 2013). The aim of this study is to evaluate the predictive ability of
experiencing a cardiovascular event (CVE) via these 2scores in the CKD
population. MATERIAL AND METHODS: Prospective, observational study of 400
prevalent patients with CKD (stages 4 and 5 according the KDOQI; not on
dialysis). Cardiovascular risk was calculated according to the 2scores and the
predictive capacity of cardiovascular events (atherosclerotic events: myocardial
infarction, ischaemic and haemorrhagic stroke, peripheral vascular disease; and
non-atherosclerotic events: heart failure) was analysed. RESULTS: Forty-nine
atherosclerotic cardiovascular events occurred in 40.3+/-6.6 months of follow-up.
Most of the patients were classified as high CVR by both scores (59% by the FRS
CVD and 75% by the ASCVD). All cardiovascular events occurred in the high CVR
patients and both scores (FRS-CVD log-rank 12.2, P<.001, HR 3.1 [95% CI: 1.3-7.1]
P: 0.006 and ASCVD log-rank 8.5 P<.001, HR 3.2 [95% CI: 1.1-9.4] P: 0.03) were
independent predictors adjusted to renal function, albuminuria and previous
cardiovascular events. CONCLUSION: The cardiovascular risk scores (FRS-CVD and
ASCVD [AHA/ACC 2013]) can estimate the probability of atherosclerotic
cardiovascular events in patients with CKD regardless of renal function,
albuminuria and previous cardiovascular events.
PMID- 28495397
TI - Safety profile and long-term engraftment of human CD31+ blood progenitors in bone
tissue engineering.
AB - BACKGROUND: Endothelial progenitor cells (EPCs) participate in angiogenesis and
induce favorable micro-environments for tissue regeneration. The efficacy of EPCs
in regenerative medicine is extensively studied; however, their safety profile
remains unknown. Therefore, our aims were to evaluate the safety profile of human
peripheral blood-derived EPCs (hEPCs) and to assess the long-term efficacy of
hEPCs in bone tissue engineering. METHODS: hEPCs were isolated from peripheral
blood, cultured and characterized. beta tricalcium phosphate scaffold (betaTCP,
control) or 106 hEPCs loaded onto betaTCP were transplanted in a nude rat
calvaria model. New bone formation and blood vessel density were analyzed using
histomorphometry and micro-computed tomography (CT). Safety of hEPCs using
karyotype analysis, tumorigenecity and biodistribution to target organs was
evaluated. RESULTS: On the cellular level, hEPCs retained their karyotype during
cell expansion (seven passages). Five months following local hEPC
transplantation, on the tissue and organ level, no inflammatory reaction or
dysplastic change was evident at the transplanted site or in distant organs.
Direct engraftment was evident as CD31 human antigens were detected lining vessel
walls in the transplanted site. In distant organs human antigens were absent,
negating biodistribution. Bone area fraction and bone height were doubled by hEPC
transplantation without affecting mineral density and bone architecture.
Additionally, local transplantation of hEPCs increased blood vessel density by
nine-fold. CONCLUSIONS: Local transplantation of hEPCs showed a positive safety
profile. Furthermore, enhanced angiogenesis and osteogenesis without mineral
density change was found. These results bring us one step closer to first-in
human trials using hEPCs for bone regeneration.
PMID- 28495398
TI - True and false contraindications to vaccines.
AB - Nowadays, the awareness of risks related to infectious diseases has decreased,
whereas THE perception of risks related to vaccination is growing. Therefore, it
may be difficult for health care providers to convince people of the importance
of vaccination and adherence to the immunisation schedule. Selected situations
that might raise uncertainties about vaccine recommendations are discussed in
order to help health care providers to identify real and perceived
contraindications to vaccines, and cases to be referred to specialised pre
vaccination consultation due to an increased risk of adverse events to vaccines.
PMID- 28495400
TI - Rapid breakthrough of 131I in an in vitro human epidermis model.
AB - Skin contamination with radionuclides may cause local radiation damage, but also
systemic distribution if the nuclides penetrate the epidermal membrane. Detailed
information of the skin absorption of radionuclides is of importance for e.g.
dose estimations and development of decontamination strategies. In the present
study, penetration of 131I through human epidermis was studied using an in vitro
flow through diffusion chamber. Epidermis was exposed to a Na131I-solution, used
in nuclear medicine, and the potential concentration-dependency of skin
penetration was examined by including two concentrations of non-radioactive NaI.
Penetration of 131I occurred after a few minutes of exposure and steady state
penetration rate was obtained after about 50-70min independently of the iodine
concentration and receptor solution used. The two receptor solutions evaluated;
phosphate buffered saline solution and an ethanol and water-mixture (1:1),
resulted in significantly higher penetration rate of 131I using the ethanol and
water-mixture. The penetration of iodine was calculated to be concentration
dependent independently of the receptor solution utilized. In addition,
radioactive iodine did not accumulate in epidermis in the in vitro-model used. In
conclusion, the present study provides detailed information on the rapid iodine
penetration at the early phase of radionuclide exposure, defined as the first
30min of the experiment, and is clearly suitable for decontamination studies. In
addition, methodological aspects, e.g. impact of the receptor solution, should
carefully be considered in studies of radionuclide skin penetration using in
vitro-techniques.
PMID- 28495399
TI - Evaluation of Toll-like-receptor gene family variants as prognostic biomarkers in
rheumatoid arthritis.
AB - Rheumatoid arthritis (RA) is a systemic autoimmune disease whose main feature is
persistent joint inflammation. Toll-like receptors (TLRs) play critical roles in
the activation of innate and adaptive immune responses, and influence the
activity of NFkappaB, a key player in chronic inflammation. We aimed at
investigating the association of TLR allelic variants with susceptibility and
severity of RA through a systematic, high-throughput, analysis of TLR genes. All
coding exons and flanking regions of nine members of the TLR family (TLR1-9) were
analyzed in 66 patients with RA and 30 healthy controls by next generation
sequencing. We focussed on three single allelic variants, N248S in TLR1, Q11L in
TLR7 and M1V in TLR8 based on the allelic frequencies in both patient and control
populations, the predicted impact on protein function and the novelty in RA
research. Analysis of these selected variants in a larger cohort of 402 patients
with RA and in 208 controls revealed no association with susceptibility. However,
the M1V allele was associated with a lower need for disease-modifying
antirheumatic drugs (DMARDs) (p=0.008) and biologic treatments (p=0.021).
Functional studies showed that the M1V variant leads to a reduced production of
inflammatory cytokines, IL-1beta, IL-6 and TNFalpha, in response to TLR8
agonists. Thus, the presence of this variant confers a significant protective
effect on disease severity. These results show for the first time the association
between the M1V variant of TLR8 and reduced disease severity in RA, which could
have prognostic value for these patients.
PMID- 28495402
TI - Associations of tumor necrosis factor-alpha-308 polymorphism with dengue
infection: A systematic review and meta-analysis.
AB - Inconsistency of reported associations between the tumor necrosis factor-alpha
308 (TNFalpha-308) polymorphism (rs1800629) and dengue virus infection prompted a
meta-analysis, to obtain more precise estimates. A literature search yielded 14
case-control studies. We calculated pooled odds ratios (OR) and 95% confidence
intervals in three groups according to severity, dengue fever (DF), dengue
hemorrhagic fever (DHF) and dengue (DEN) using standard genetic models. Pooled
ORs were subjected to modifier treatment where re-analysis was confined to Hardy
Weinberg compliant (HWC) studies. Heterogeneity of outcomes warranted examining
their sources with outlier treatment. In subgroup analysis, we compared Asian and
South/Central American (SCA)/Brazilian effects. Overall pooled outcomes yielded
no significant effects (OR 0.66-1.44, P=0.08-0.96). In the dominant-codominant
model, pooled effects were heterogeneous (I2=47%-71%) which was lost/reduced
(I2=0%-43%) when outlier treatment was applied. This also yielded significant
associations (OR 0.68-0.77, P=0.02-0.05). Our results are best seen in the Asian
subgroup, which in itself already yielded significant effects in DEN (OR 0.62
0.67, P=0.01-0.02). These reduced risk findings were significant from the tests
of interaction (P=0.001-0.02) which highlights the protective effects of TNFalpha
308 among Asians. TNFalpha-308 effects on dengue are based on significance and
non-heterogeneity of the post-outlier outcomes in the dominant and codominant
models. Here, pooled effects may also be ethnic specific, where Asians are
protected but not SCA. Both modified and Asian effects are up to 38% protective.
PMID- 28495401
TI - Transcriptomic analysis of porcine PBMCs in response to FMDV infection.
AB - Foot-and-mouth disease (FMD) is a significant zoonotic infectious disease. It has
an important economic impact throughout the world. As well, it is a considerable
threat to food security. At present, the molecular mechanism of FMDV infection is
not clear to a large extent. Innate immune response is the first line of defense
against infectious diseases. The systematic analysis of the host immune response
to infection has an important role in understanding the pathogenesis of
infection. However, there are few reports about effect of immune regulation on
virus replication in the interaction of virus and host cellular. High-throughput
RNA-seq technology as a powerful and efficient means for transcript analysis
provides a new insight into FMDV study. In this study, RNA extracted from pig
PBMCs infected with O subtype FMDV at 4 dpi. A total of 29942658 and 31452917
Illumina read pairs were obtained from the non-infected (NI) group and infected
(I) group, respectively. The clean bases for all samples are 3.61G (NI group) and
3.79G (I group), respectively. The clean reads of the NI and I group that mapped
to pig genome data were 47195073 (81.82%) and 46556714 (76.85%), respectively.
Most of the clean reads were distributed in the exon region, followed by intron
region and intergenic region. Differently expressed (DE) genes were analyzed
using edgeR software. 451 genes were differentially expressed between the
infected and the non-infected groups. According to the comparison analysis, more
genes were down-regulated in the non-infected samples than in those infected with
FMDV.66 out of 451 genes were down-regulated, 385 out of 451 genes were up
regulated following FMDV infection. For function classification and pathway
analysis, among 17741 assembled unigenes, there are 349 genes which are different
genes of GO notes. Moreover, 49 genes were down-regulated, 300 genes were up
regulated associate with GO term. 1621 were successfully annotated by GO
assignments, belonging to one or more of the three categories: biological
process, cellular component, and molecular function. According to KEGG
analysis,the main pathway was represented including protein processing in
endoplasmic reticulum, phagosome, cell cycle and cytokine-cytokine receptor
interaction. Some key DE genes related to immune process and signaling pathways
were analyzed and quantified by RT-PCR. This is the first systematical
transcriptome analysis of pig PBMCs infected by FMDV. These findings will help us
better understand the host Cell-FMDV interaction and its relationship to
pathogenesis, as well as contribute to the prevention and control of FMDV.
PMID- 28495403
TI - Effect of insecticide-treated bed nets on house-entry by malaria mosquitoes: The
flight response recorded in a semi-field study in Kenya.
AB - Insecticide-treated nets are currently a major tool to reduce malaria
transmission. Their level of repellency affects contact of the mosquito with the
net, but may also influence the mosquito's entry into the house. The response of
host-seeking malaria mosquitoes approaching the eave of an experimental house was
recorded within a large screen house. We compared entry- and exit rates in
relation to the presence in the house of different insecticide-treated bed nets
(ITNs) with an untreated net. Mosquitoes were lured towards the house by
dispensing a synthetic host-odour blend from within the net in the house.
Complementary WHO bioassays revealed that the treated nets caused high knock-down
and mortality responses to the Anopheles gambiae sensu stricto strain tested.
The proportion of mosquitoes that came into view of the cameras and subsequently
entered the house did not differ between treated nets and the untreated net.
Treated nets did not affect proportions of mosquitoes that exited the house and
departed from view around the eave. However, the percentage of house-leaving and
re-entering mosquitoes when an insecticide- treated net was present, was lower
than in the presence of an untreated net. Our results indicated that there was no
spatial repellent effect from pyrethroid-treated nets that influences house-entry
at eave level. It is argued that the toxic effect of treated bed nets resulted in
a reduced number of mosquitoes re-entering the house, which could thereby affect
malaria transmission in neighbouring, unprotected houses.
PMID- 28495404
TI - Does Aedes albopictus (Diptera: Culicidae) play any role in Usutu virus
transmission in Northern Italy? Experimental oral infection and field evidences.
AB - This study evaluated the vector competence of Aedes albopictus in transmitting
USUV after oral infection under laboratory conditions. Ae. albopictus showed a
low vector competence for USUV, although the positive body sample found with a
very high number of viral copies at one week post infection indicates that a
replication in the mosquito body can occur, and that USUV can escape the midgut
barrier. Field data from an extensive entomological arboviruses surveillance
program showed a relevant incidence of Ae. albopictus USUV positive pools in the
period 2009-2012 while all pools were negative from 2013 on. No conceivable
explanation regarding this field evidence was addressed, suggesting that
attention must be paid to the trend of development of this vector-pathogen
association, being aware of the potential rapid arbovirus' adaptation to new
vectors, to prevent possible new disease's emergence.
PMID- 28495405
TI - Trypanosoma cruzi I: Towards the need of genetic subdivision?, Part II.
AB - Chagas disease is a complex zoonosis caused by the kinetoplastid parasite
Trypanosoma cruzi. This protozoan exhibits remarkable genetic diversity evinced
in at least six Discrete Typing Units (DTUs) with the foreseen emergence of a
genotype associated to bats (TcBat). T. cruzi I is the DTU with the broadest
geographical distribution and associated to severe cardiomyopathies. In 2011, we
published a review questioning the need for genetic subdivision within TcI.
However, after six years of intensive research. Herein, we attempted to determine
if TcI should be subdivided or not in the light of the current genetic,
biological, clinical and ecological data. The future perspectives are discussed.
PMID- 28495407
TI - In Reply: The Only Thing We Have to Blame Is Blame Itself.
PMID- 28495408
TI - Is the Level of Nitric Oxide in the Dental Follicular Tissues of Impacted Third
Molars With a History of Recurrent Pericoronitis a True Marker of Oxidative
Stress?
AB - PURPOSE: Nitric oxide (NO) is an indicator of oxidative stress in several
tissues. Its role in dental follicular (DF) tissues of impacted third molars with
a history of recurrent pericoronitis is not well elucidated. The present study
compared NO levels between inflamed and noninflamed DF tissues of impacted third
molars with a history of recurrent pericoronitis. MATERIALS AND METHODS: A cross
sectional study was designed. The study sample included inflamed DF tissues (test
group) with certain local inflammatory symptoms, such as pain, tenderness,
swelling, and erythema and noninflamed DF tissues (control group) without local
inflammatory symptoms of impacted mandibular third molars. Each patient
contributed only 1 specimen to the samples. All tissues samples were
biochemically investigated for NO levels as an indicator of oxidative stress. The
primary predictor variable was inflammatory status; secondary predictor variables
were age and gender. The primary outcome variable was NO level. Descriptive and
comparative analyses were conducted. RESULTS: The test group consisted of 57
patients (28 men, 29 women; mean age, 23.28 +/- 5.16 yr) and the control group
consisted of 57 patients (30 men, 27 women; mean age, 23.02 +/- 5.42 yr). No
relevant intergroup differences were noted for demographic findings such as age
and gender. NO levels were significantly higher in inflamed DF tissues of
impacted third molars than in noninflamed DF tissues (P < .05). CONCLUSION:
Results of this study showed that NO might be used as an indicator of oxidative
stress and the necessity to remove impacted mandibular third molars with a
history of recurrent pericoronitis.
PMID- 28495406
TI - Nuclear Receptor Function through Genomics: Lessons from the Glucocorticoid
Receptor.
AB - Unlocking the therapeutic potential of the glucocorticoid receptor (GR) has
motivated a search for small molecules that selectively modulate its ability to
activate or repress gene transcription. Recently, breakthrough studies in the
field of genomics have reinvigorated debate over longstanding transcriptional
models explaining how GR controls tissue-specific gene expression. Here, we
highlight these genomic studies with the dual goals of advancing understanding of
nuclear receptor-mediated transcription and stimulating thought on the
development of anti-inflammatory and immunosuppressive ligands for GR that have
reduced harmful effects on metabolism.
PMID- 28495409
TI - Effect of Asymptomatic Visible Third Molars on Periodontal Health of Adjacent
Second Molars: A Cross-Sectional Study.
AB - PURPOSE: Evidence that asymptomatic third molars (M3s) negatively affect their
adjacent second molars (A-M2s) is limited. The present study evaluated the
association between visible M3s (V-M3s) of various clinical status with the
periodontal pathologic features of their A-M2s. PATIENTS AND METHODS: Subjects
with at least 1 quadrant having intact first and second molars, either with V-M3s
and symptom free or without adjacent V-M3s, were enrolled in the present cross
sectional investigation. Periodontal parameters, including plaque index (PLI),
bleeding on probing (BOP), probing pocket depth (PPD), and at least 1 site with a
PPD of 5 mm or more (PPD5+), obtained from M2s were analyzed according to the
presence or absence of V-M3s or the status of the M3s. The chi2 test or t test
was used to compare the mean PLI, PPD, BOP percentage, and PPD5+ percentage. The
association of PPD5+ with V-M3 status was assessed using a multivariable logistic
regression model (quadrant-based analysis), and variances were adjusted for
clustered observations within subjects. RESULTS: In total, 572 subjects were
enrolled in the study, and 423 had at least 1 V-M3. At the in-quadrant level, the
presence of a V-M3 significantly increased M2 pathologic parameters, including
PLI, PPD, BOP, and PPD5+. When analyzed using a multivariate logistic regression
model, impacted M3s and normally erupted M3s significantly elevated the risk of
PPD5+ on their A-M2s (odds ratio 3.20 and 1.67, respectively). Other factors
associated with an increased odds of PPD5+ were mandibular region and older age.
Finally, the patient-matched comparison showed that the percentage of BOP and
PPD5+ on M2s increased when V-M3s were present. CONCLUSIONS: Irrespective of
their status, the presence of V-M3s is a risk factor for the development of
periodontal pathologic features in their A-M2s. Although the prophylactic removal
of asymptomatic V-M3s remains controversial, medical decisions should be made as
early as possible, because, ideally, extraction should be performed before
symptom onset.
PMID- 28495410
TI - A Case-and-Control, Multisite, Positive Controlled, Prospective Study of the
Safety and Effectiveness of Immediate Inferior Alveolar Nerve Processed Nerve
Allograft Reconstruction With Ablation of the Mandible for Benign Pathology.
AB - PURPOSE: This study determined whether immediate reconstruction of the inferior
alveolar nerve with a long (>4.5 cm) processed nerve allograft (PNA) in
conjunction with simultaneous ablation and reconstruction of the mandible would
be effective in safely restoring subjective sensation and achieving functional
sensory recovery. MATERIALS AND METHODS: Patients (5 to 70 yr old) requiring
resection of the unilateral or bilateral mandible for benign pathology were
included. The graft had to be longer than 4.5 cm. Results of sensory nerve tests
and 3 different surveys (Direct Path, Numerical Rating Scale, Word Choice) were
collected before surgery and at 3, 6, and 12 months after surgery. Safety data
were recorded. RESULTS: Twenty-six patients participated in this study. Three
patients served as positive controls (no nerve repair). Five in the repair group
and 1 in the positive control group were lost to follow-up. Data during a 1-year
period were collected on 18 patients (7 male and 11 female; mean age, 26.4 yr;
range, 10 to 64 yr). The mean length of the PNA was 62.7 mm (range, 45 to 70 mm).
Seventeen of 18 patients had S4 sensory scores preoperatively and the
postoperative score was S4 at 3 months in 3, at 6 months in 3, and at 1 year in
12. Scores for positive control patients never exceeded S2. Numerical rating
scales and word choices were not statistically different from presurgical scores
at 6 and 12 months. There were no adverse events. CONCLUSIONS: The PNA is safe
and effective when immediately inserted with resection and reconstruction of the
mandible: 90% of patients achieved functional sensory recovery and reported
similar sensations to preoperative subjective values.
PMID- 28495411
TI - Is Low-Level Laser Therapy Effective for Treatment of Neurosensory Deficits
Arising From Sagittal Split Ramus Osteotomy?
AB - PURPOSE: This study investigated the effectiveness of low-level laser therapy
(LLLT) for treating neurosensory impairment after bilateral sagittal split
osteotomy (BSSO). MATERIALS AND METHODS: This randomized, double-blinded, split
mouth trial included patients requiring BSSO. After surgery, 1 side of each
patient was randomly assigned to laser therapy and the other side served as the
control. At 24, 48, and 72 hours after surgery, LLLT was accomplished by
intraoral application of a 660-nm laser around the surgical site (200 mW, 10
seconds, 2 J, 1.5 J/cm2) followed by extraoral irradiation by an 810-nm laser
(200 mW, 10 seconds, 2 J, 7 J/cm2) along the distribution of the inferior
alveolar nerve. Subsequently, extraoral irradiation was repeated 2 times per week
for 3 weeks along the path of the inferior alveolar nerve, lower lip, and chin.
On the control side, the treatment was similar to the laser side but with laser
simulation. The main outcome was assessing nerve damage by a "2-point
discrimination test" before and up to 60 days after surgery. RESULTS: The sample
consisted of 16 patients. No significant difference was found between the laser
and control sides before and after surgery and on postoperative days 15 and 30 (P
> .05). The 2-point discrimination distance was significantly shorter on the
laser side than on the control side on postoperative days 45 and 60 (P < .05).
CONCLUSION: LLLT was effective in the treatment of neurosensory disturbances
arising from BSSO. Therefore, LLLT can be recommended to accelerate the recovery
of sensory aberrations in patients undergoing BSSO.
PMID- 28495412
TI - Radiofrequency Microdebridement Versus Surgical Decompression for Achilles
Tendinosis: A Randomized Controlled Trial.
AB - Achilles tendinosis is primarily managed nonoperatively with activity
modification and physiotherapy, although surgery can be required. This has
classically involved surgical decompression of the Achilles tendon, although the
use of radiofrequency microdebridement has been suggested as a novel minimally
invasive alternative. We present a randomized controlled trial comparing
radiofrequency microdebridement using the Topaz(r) microdebrider wand and
traditional surgical decompression. All patients with Achilles tendinosis
referred to a single surgeon and meeting the inclusion criteria were invited to
participate in our single-blinded, randomized controlled study. The Victorian
Institute of Sports Assessment-Achilles (VISA-A) questionnaire and the visual
analog scale were used as measures at baseline and 6 months postoperatively. From
2009 to 2014, 16 patients were randomized to traditional decompression treatment
and 20 to Topaz(r) treatment. All surgical procedures were performed as day-case
procedures with the patient under general anesthetic by a single surgeon. No
significant differences were found between the groups in demographic data. At 6
months after intervention, both groups demonstrated an improvement in the
Victorian Institute of Sports Assessment-Achilles and visual analog scale scores
compared with baseline, with no difference found between treatment modalities at
6 months. The Topaz(r) microdebrider resulted in variable outcomes after surgery
and is not without complications. Regarding the patient-reported outcome
measures, Topaz(r) conferred no additional benefit compared with traditional
surgical decompression and we have stopped using Topaz(r) in our treatment of
Achilles tendinosis.
PMID- 28495413
TI - The Central Vacuole of the Diatom Phaeodactylum tricornutum: Identification of
New Vacuolar Membrane Proteins and of a Functional Di-leucine-based Targeting
Motif.
AB - Diatoms are unicellular organisms evolved by secondary endosymbiosis. Although
studied in many aspects, the functions of vacuolar-like structures of these
organisms are rarely investigated. One of these structures is a dominant central
vacuole-like compartment with a marbled phenotype, which is supposed to represent
a chrysolaminarin-storing and carbohydrate mobilization compartment. However,
other functions as well as targeting of proteins to this compartment are not
shown experimentally. In order to study trafficking of membrane proteins to the
vacuolar membrane, we scanned the genome for intrinsic vacuolar membrane proteins
and used one representative for targeting studies. Our work led to the
identification of several proteins located in the vacuolar membrane as well as
the sub-compartmentalized localization of one protein. In addition, we show that
a di-leucine-based motif is an important signal for correct targeting to the
central vacuole of diatoms, like it is in plants.
PMID- 28495414
TI - The NHS is no place for immigration enforcement.
PMID- 28495415
TI - Rhinovirus - From bench to bedside.
AB - Rhinovirus has been neglected in the past because it was generally perceived as a
respiratory virus only capable of causing mild common cold. Contemporary
epidemiological studies using molecular assays have shown that rhinovirus is
frequently detected in adult and pediatric patients with upper or lower
respiratory tract infections. Severe pulmonary and extrapulmonary complications
are increasingly recognized. Contrary to popular belief, some rhinoviruses can
actually replicate well at 37 degrees C and infect the lower airway in humans.
The increasing availability of multiplex PCR panels allows rapid detection of
rhinovirus and provides the opportunity for timely treatment and early
recognition of outbreaks. Recent advances in the understanding of host factors
for viral attachment and replication, and the host immunological response in both
asthmatic and non-asthmatic individuals, have provided important insights into
rhinovirus infection which are crucial in the development of antiviral treatment.
The identification of novel drugs has been accelerated by repurposing clinically
approved drugs. As humoral antibodies induced by past exposure and vaccine
antigen of a particular serotype cannot provide full coverage for all rhinovirus
serotypes, novel vaccination strategies are required for inducing protective
response against all rhinoviruses.
PMID- 28495416
TI - Invasive fungal rhinosinusitis presenting as Bell's palsy in a kidney and liver
transplant recipient.
PMID- 28495417
TI - False positive ketamine urine immunoassay screen result induced by quetiapine: A
case report.
AB - Ketamine immunoassay urine drug screen (UDS) is commonly used in Taiwan. However,
there was limited report about possible drug which may cause false positive
results in ketamine screen test. We report two cases who used quetiapine showed
positive in ketamine urine immunoassay screen initially, and found to be false
positive in confirmation test. Clinicians should be aware of the false positive
result of ketamine UDS caused by currently used medication.
PMID- 28495418
TI - Structural study of the cremaster muscle in patients with retractile testis.
AB - OBJECTIVE: To analyze the structure of the cremaster in patients with retractile
testis (RT), comparing the distribution of nerves, elastic system and muscles
with patients having cryptorchidism and inguinal hernia (IH). PATIENTS AND
METHODS: We studied 31 patients, 17 with RT (mean age=5.17years); 9 with IH (mean
age=2.6) and 5 with cryptorchidism (mean age=3). A cremaster biopsy was performed
and submitted to routine histological processing and studied using histochemistry
and immunohistochemistry. The samples were photographed under an Olympus BX51
microscope. The images were processed with the Image J software and the cremaster
muscle structures were quantified. Means were compared statistically using ANOVA
and the unpaired t-test (p<0.05). RESULTS: There were no differences (p=0.08) in
diameter of muscle fiber between the groups. The muscle fiber density differed
between patients with RT and IH (p=0.02): RT (mean=17.71%, SD=16.67), IH
(mean=38.06%, SD=14) and cryptorchidism (mean=21.47%, SD=16.18). There was no
difference (p=0.07) in the density of elastic fibers in the three groups. We
observed a lower concentration of cremaster nerves of patients with RT compared
with IH (p=0.0362): RT (mean=1.72%, SD=0.58), IH (mean=3.28% SD=0.94) and
cryptorchidism (mean=2.52%, SD=0.53). CONCLUSIONS: Retractile testis is not a
normal variant, and presented a similar cremaster muscle structure as in patients
with cryptorchidism. LEVEL OF EVIDENCE: II; prospective comparative study.
PMID- 28495419
TI - Factors associated with thrombotic complications in pediatric patients with
vascular malformations: Methodological issue.
PMID- 28495420
TI - The Vacuum Bell device as a sternal lifter: An immediate effect even with a short
time use.
AB - BACKGROUND: To minimize cardiac perforation during the minimally invasive repair
of pectus excavatum (MIRPE), several surgeons have suggested using a suction
device to intraoperatively lift the sternum. Whether or not this technique is
effective for all PE patients is not yet known. As such, our aim was to quantify
the extent to which a suction device is capable of lifting the sternum with a
short duration of use. METHODS: 30 PE patients received a low-dose CT scan as
part of standard PE evaluation. A Vacuum Bell suction was then applied for only
two minutes, and a repeat CT scan was obtained only at the deepest point of the
chest wall deformity. We compared chest dimensions before and after Vacuum Bell
suction. RESULTS: The Vacuum Bell lifted the sternum in all 29 patients included
in the analysis. The absolute change in depth ranged from 0.29 to 23.67mm
(M=11.02, SD=6.05). The average improvement in Haller index was 0.76. The suction
was most effective for individuals with low BMI and smaller chest depths.
Efficacy was not associated with gender, age, or chest morphology. CONCLUSIONS:
The Vacuum Bell device effectively lifted the sternum in PE patients with
different demographics and chest morphologies. Future research is needed to
address whether or not the device reduces risk of cardiac perforation during
MIRPE. LEVELS OF EVIDENCE: Prognosis Study Level IV.
PMID- 28495421
TI - Association of aldose reductase gene polymorphism (C-106T) in susceptibility of
diabetic peripheral neuropathy among north Indian population.
AB - AIM/HYPOTHESIS: Polymorphism in aldose reductase (ALR) gene at nucleotide C(
106)T (rs759853) in the promoter region is associated with susceptibility to
development of diabetic peripheral neuropathy. The aim of this study was to
detect the association of the C (-106)T polymorphism of ALR gene and its
frequency among patients with type 2 diabetes mellitus with and without
peripheral neuropathy. METHODS: The study subjects were divided into three
groups. Group I included 356 patients with diabetes having peripheral neuropathy.
Group II included 294 patients with diabetes without peripheral neuropathy and
group III included 181 healthy subjects. Genotyping of ALR C(-106)T SNPs was
performed using polymerase chain reaction-restriction fragment length
polymorphism (PCR-RFLP) and direct sequencing methods. The genetic risk among the
groups was compared and tested by calculating odds ratio with 95% class interval.
RESULTS: ALR 106TT genotype was significantly higher in group I compared to group
II with an odds ratio of 2.12 (95% CI: 1.22-3.67; p<0.01). Recessive model (CC+CT
vs. TT), as well as T allele distribution also showed significant association to
develop neuropathy with relative risk of 1.97 (95% CI: 1.16-3.35; p<0.01) and
1.36 (95% CI: 1.07-1.72; p=0.01) respectively. CONCLUSION/INTERPRETATION: In
conclusion, the ALR C-106T polymorphism was associated with higher risk of
peripheral neuropathy in patients with type 2 diabetes mellitus.
PMID- 28495422
TI - Reduced frequency of severe hypoglycemia at mild ambient temperatures between 10
and 20 degrees C: A population-based study under marine west coast climate
conditions.
AB - AIMS: To determine the association between ambient temperature and severe
hypoglycemia. METHODS: This was a prospective observational study performed in a
prehospital setting. Data from the Emergency Medical Service in Hamburg (Germany)
and data from the local weather station were evaluated over a 5-year period.
Lowess-regression analysis was conducted to assess the relationship between
ambient temperature and frequency of severe hypoglycemia. Additionally, three
temperature-ranges were defined in order to compare them with each other with
regard to frequency of severe hypoglycemia (<10 degrees C vs. 10-20 degrees C vs.
>20 degrees C). RESULTS: In 2592 patients severe hypoglycemia was diagnosed and
treated by emergency physicians (T1DM: n=829/32%; T2DM: n=1763/68%). The median
age of patients was 64 (57-72 [20-85]) years. Compared to mild temperatures (10
20 degrees C) the frequency of severe hypoglycemia increased significantly at
temperatures above 20 degrees C (+18% (95%-CI: [7%; 22%], p=0.007) and below 10
degrees C (+15% (95%-CI: [6%; 24%], p<0.001). CONCLUSIONS: The results suggest
the existence of a "thermal comfort zone" covering a temperature range from 10 to
20 degrees C in which the frequency of severe hypoglycemia was significantly
lower than below 10 degrees C and above 20 degrees C.
PMID- 28495423
TI - The current evidence of statin use affecting glioblastoma prognosis.
AB - Cholesterol-lowering statins have been postulated to improve cancer outcomes by
many unconfirmed mechanisms. The prognosis of glioblastoma (GBM) remains dismal,
and there is a paucity of evidence regarding the potential for preoperative
statins to exert a benefit upon prognosis. In light of a recent report, the
current evidence in the literature regarding statin use affecting GBM prognosis
is discussed.
PMID- 28495424
TI - Clinical and radiographic outcomes following hinge fracture during open-door
cervical laminoplasty.
AB - To investigate the clinical and radiographic fate of fractured hinges in open
door cervical laminoplasty, 135 segments of 36 patients who had undergone follow
up for more than two years after open-door cervical laminoplasty due to
compressive cervical myelopathy were reviewed clinically and radiographically.
Hinge fractures were identified by the intraoperative finding of obvious
instability or click sounds (an obvious fracture), or by immediate postoperative
computed tomography (CT) images showing a discontinuity of both the inner and
outer cortex or a displacement of more than 1mm at the lamina hinge site (an
occult fracture). At two years post-surgery, union and displacement of the
fractured hinges were evaluated with CT and the clinical outcome was assessed by
the Japanese Orthopedic Association (JOA) and Neck Disability Index (NDI) scores.
Immediate postoperative CT scans revealed 28 hinge fractures in 16 patients. Only
three fractures were identified during surgery, with most being identified on
postoperative CT. Nineteen laminae showed non-displaced cortical discontinuity,
five were anteriorly displaced by more than 1mm, and four were displaced
posteriorly. Twenty-five laminae (89.3%) had achieved union according to the two
year postoperative CT scan. No de novo neurologic symptoms were found to be
associated with hinge fracture. The two-year postoperative JOA and NDI scores did
not differ significantly between patients with or without a hinge fracture. Most
fractures at the hinge site occurred without intraoperative recognition, and
usually re-unified without significant displacement or adverse clinical effects.
When hinge fractures occur, careful observation without additional intervention
is recommended.
PMID- 28495425
TI - Volume-staged stereotactic radiosurgery for large intracranial arteriovenous
malformations.
AB - Stereotactic radiosurgery (SRS) is an effective treatment option for intracranial
arteriovenous malformations (AVM). However, the treatment of large AVMs (nidus
volume >=12cm3) with single-session SRS alone yields generally poor outcomes.
Volume-staged SRS (VS-SRS) is a therapeutic strategy for large AVMs which seeks
to avoid the disadvantages of single-session SRS, but reports regarding its
efficacy remain limited. The aim of this retrospective cohort study is to assess
the outcomes of VS-SRS for large AVMs. We identified all AVM patients who
underwent VS-SRS at our institution from 2000 to 2015 with >=12months follow-up.
Baseline and outcomes data were analyzed. A total of 12 patients were selected
for the study cohort, with a median age of 30years. The median maximum AVM
diameter and nidus volume were 4.3cm and 13.6cm3, respectively. The Spetzler
Martin grade was III and IV each in six AVMs (50%). All patients underwent VS-SRS
in two stages, and the median margin dose was 17Gy for both VS-SRS procedures.
The median time interval between the two procedures was three months. After a
median radiologic follow-up duration of 39months, the median degree of AVM volume
reduction (evaluable in nine patients) was 87% (range 12-99%). The rates of
radiologically evident, symptomatic, and permanent radiation-induced changes were
58%, 25%, and 8%, respectively. There were no cases of post-SRS hemorrhage. VS
SRS substantially reduces the size of large AVMs. A potential role for VS-SRS may
be to facilitate subsequent definitive intervention to obliterate a shrunken,
residual nidus.
PMID- 28495426
TI - Pressure volume curves in cirrhosis: More than meets the eye.
PMID- 28495427
TI - O-GlcNAcylation: Undesired tripmate but an opportunity for treatment in NAFLD
HCC.
PMID- 28495428
TI - Cytotoxic bilirubin metabolites overlooked so far.
PMID- 28495429
TI - Superoxide-hydrogen peroxide genetic imbalance modulates differentially the
oxidative metabolism on human peripheral blood mononuclear cells exposed to
seleno-L-methionine.
AB - Superoxide-hydrogen peroxide (S-HP) imbalance genetically caused by a gene
polymorphism in the human manganese superoxide dismutase enzyme (Val16Ala-MnSOD)
is associated with several diseases. Into mitochondria, MnSOD catalyses
superoxide radical producing HP and oxygen. Ala-MnSOD genotype presents a high
MnSOD efficiency and generates the highest HP concentrations that has been
associated with the risk of several cancer types. Cellular selenoenzymes
glutathione peroxidase and thioredoxin reductase (TrxR) and catalase (CAT) are
essential to HP removal produced in excess in cells. Since, synthesis and
activities of selenoenzymes are selenium dependent, we hypothesized that AA-MnSOD
cells could have an improvement on antioxidant status undergoing Seleno-L
methionine (SeMet) treatment. This study performed an in vitro protocol to
evaluate the response of peripheral blood mononuclear cells (PBMC) carriers of
different Val16Ala-MnSOD genotypes exposed to SeMet. SeMet effects on cell
viability, apoptosis induction and modulation of oxidative variables were
determined using spectrophotometric, flow cytometry, fluorimetric and
immunoassays. Gene modulation of antioxidant enzymes was also performed by qRT
PCR. From an initial protocol using heterozygous (AV) cells was determined that
1nM SeMet presented a cytoprotective effect. However, whereas this concentration
did not change AA viability, in VV cells it was cytotoxic by increasing necrosis
events. SeMet induced higher selenoenzymes levels in AA and VV cells and
decreased oxidative markers levels including DNA damage. The results suggest a
pharmacogenetic positive response of SeMet effect on AA-cells. Future studies in
vivo could be essential to evaluate the potential clinical impact of S-HP
imbalance after use of foods or supplements containing SeMet.
PMID- 28495430
TI - Patient Versus Physician Variation in Use of Transradial Percutaneous Coronary
Intervention.
AB - The prevalence of radial access for transradial catheterization remains low in
the United States, occurring in only 28% of cases in the National Cardiovascular
Data Registry (NCDR) CathPCI. It is unknown whether the low adoption rate has
been influenced by patient characteristics or is more operator dependent. In a 10
center study, we compared clinical and demographic characteristics among 323
radial and 1,506 femoral access percutaneous coronary intervention (PCIs)
performed by 65 interventionists capable of radial PCI. We created a hierarchical
logistic regression model to identify operator and patient characteristics
associated with radial PCI and the median rate ratio to quantify the variation
across operators. A subset was interviewed to assess health literacy and
preferences in shared medical decision making. Radial access was used in 17.7% of
patients. Patient factors associated with lower rate of radial PCI were previous
PCI (33.4% vs 41.4%, p = 0.008), history of coronary artery bypass graft (8.4% vs
23.0%, p <0.001), and chronic total occlusion PCI (10.2% vs 17.9%, p <0.001).
Operator characteristics associated with lower rate of radial PCI are being
older, being longer in practice, lower number of publications, and Southern
practice location. The range of radial use across operators was 1% to 99% and the
median rate ratio was 1.97. Patients with radial access had lower health
literacy, as assessed by the Rapid Estimate of Adult Literacy in Medicine Revised
(REALM) score (6.6 +/- 2.6 vs 7.1 +/- 2.0, p = 0.03) but did not differ in their
preferences for shared decision making. In conclusion, our study demonstrates a
high degree of variability of radial access for PCI among different operators,
with few differences in patient characteristics, suggesting that improvement
efforts should focus on operators.
PMID- 28495432
TI - Changes in Coagulation and Platelet Activation Markers Following Transcatheter
Left Atrial Appendage Closure.
AB - The recommendations for antithrombotic treatment after left atrial appendage
closure (LAAC) remain empirical, and no data exist on the changes in hemostatic
markers associated with LACC. The objective of the present study is to determine
the presence, degree, and timing of changes in the markers of platelet and
coagulation activation after LAAC. Forty-three patients (mean age 76 +/- 9 years,
23 men) with atrial fibrillation who underwent successful LACC with the Watchman
(n = 27) or Amplatzer Cardiac Plug (n = 16) devices were included in the study.
Patients received antiplatelet therapy after LAAC (aspirin + clopidogrel: 27
patients; single antiplatelet therapy with aspirin or clopidogrel: 16 patients).
Prothrombin fragment 1+2 and thrombin-antithrombin III were used as markers of
coagulation activation, and soluble P-selectin and soluble CD40 ligand were used
as markers of platelet activation. Measurements of all hemostatic markers were
performed at baseline just before the procedure, followed by days 7, 30, and 180
after LAAC. Prothrombin fragment 1+2 and thrombin-antithrombin levels increased
from 0.27 nmol/L and 4.68 ng/ml, respectively, at baseline to peak values of 0.43
nmol/L and 9.76 ng/ml, respectively, at 7 days, partially returning to baseline
levels at days 30 and 180 after LAAC (p <0.001 for both markers). No clinical or
procedural factors were associated with a greater increase in the markers of
coagulation activation after LAAC. Levels of soluble P-selectin and soluble CD40
ligand did not change at any time after LAAC. In conclusion, transcatheter LAAC
is associated with significant activation of the coagulation system, yet without
evidence of significant platelet activation.
PMID- 28495433
TI - Ventricular and Supraventricular Ectopy in Subjects With Early Repolarization.
AB - Early repolarization (ER) is a common electrocardiographic (ECG) finding that is
associated with an increased risk of idiopathic ventricular fibrillation and
sudden cardiac death. This study investigated whether the presence of ER is a
predictor of ventricular and supraventricular ectopy as a marker for electrical
instability. Standard 12-lead electrocardiograms of the first follow-up in the
population-based Study of Health in Pomerania (SHIP-1) (n = 3,300, age 20 to 79
years) were analyzed to identify subjects with an ER pattern. Ventricular and
supraventricular ectopy was assessed via portable tele-ECG cards recording 2
electrocardiograms daily over the course of 4 weeks. Data of 1,630 subjects (n =
83,833 ECG card recordings, average 51.4 per subject) were analyzed for
ventricular and supraventricular ectopy using a standardized automated algorithm.
Associations of ER and several forms of arrhythmias were assessed using a 2-sided
Fisher's exact test or t test, where appropriate. Overall, prevalence of ER in
the SHIP-1 population was 4.8%. Presence of ER was not associated with the
occurrence of ventricular and supraventricular arrhythmias (p >=0.05 for all
analyses). Furthermore, subgroup analyzes for ER localization (inferior) and ST
segment morphology (horizontal/descending) did not show any association with
arrhythmic events. In conclusion, presence of the ER pattern is not associated
with an increased occurrence of ventricular or supraventricular arrhythmias as
assessed by serial ECG card recordings in this large population-based sample.
PMID- 28495431
TI - Evolution of Australian Percutaneous Coronary Intervention (from the Melbourne
Interventional Group [MIG] Registry).
AB - Percutaneous coronary intervention (PCI) continues to evolve with shifting
patient demographics, treatments, and outcomes. We sought to document the
specific changes observed over a 9-year period in a contemporary Australian PCI
cohort. The Melbourne Interventional Group is an established multicenter PCI
registry in Melbourne, Australia. Data were collected prospectively with 30-day
and 12-month follow-ups. Demographic, procedural, and outcome data for all
consecutive patients were analyzed with a year-to-year comparison from 2005 to
2013. National Death Index linkage was performed for long-term mortality
analysis; 19,858 procedures were captured over 9 years. Patient complexity and
acuity increased with a higher proportion of traditional risk factors and more
elderly patients who underwent PCI. Angiographic lesion complexity increased with
more multivessel coronary artery disease and more American College of
Cardiology/American Heart Association type B2/C lesions proceeding to PCI. The 30
day rate of death, myocardial infarction, or target vessel revascularization has
not changed nor has 12-month mortality, myocardial infarction, or major adverse
cardiovascular event rates. The strongest independent predictor of long-term
mortality was cardiogenic shock at presentation (hazard ratio [HR] 2.95, p
<0.01). Drug-eluting stent use (HR 0.83, p <0.01) and a history of dyslipidemia
(HR 0.81, p <0.01) were associated with long-term survival. In conclusion, from
2005 to 2013, we observed a cohort of higher risk clinical and angiographic
characteristics, with stable long-term mortality.
PMID- 28495434
TI - Patterns of recurrence and long-term outcomes in patients who underwent
pancreatectomy for intraductal papillary mucinous neoplasms with high grade
dysplasia: implications for surveillance and future management guidelines.
AB - BACKGROUND: While intraductal papillary mucinous neoplasms (IPMNs) with high
grade dysplasia (HGD) are thought to represent non-invasive, high-risk lesions,
its natural history following resection is unknown. METHODS: A retrospective
review of HGD-IPMN patients (1999-2015) was performed. Recurrence patterns and
clinical outcomes following pancreatectomy were analyzed and the indications for
surgery were explored based on current guidelines. RESULTS: HGD was diagnosed in
100 of 314 patients (32%) following pancreatectomy for IPMN. IPMNs were
classified as main duct, branch duct, or mixed in 15, 58 and 27 patients,
respectively. Following resection, 25 patients had low-risk residual disease in
the remnant pancreas. With a median follow-up of 35 months (range 1-129), 9
patients developed progressive or recurrent disease, 4 of whom underwent
additional pancreatectomy. Three patients developed invasive adenocarcinoma.
Median time to recurrence was 15 months (range 7-72). Based on the management
algorithm from the international consensus guidelines, resection was indicated in
76 patients (76%). Other indications for surgery included mixed-duct IPMN(13),
increased cyst size(7) and other(4). CONCLUSION: The prognosis of HGD-IPMN
following resection is good; however, HGD may be a marker for developing IPMN
recurrence or adenocarcinoma. Current guidelines regarding surgical indications
for IPMN can miss a significant number of patients with HGD.
PMID- 28495435
TI - Validation of clinical risk score for colorectal liver metastases resected in a
contemporary multicenter cohort.
AB - BACKGROUND: Recent advances in care for colorectal liver metastases (CRLM) have
lengthened 5-year survival. In this new era, prognostic tools such as the
clinical risk score (CRS) for colorectal liver metastases require reevaluation.
METHODS: Patients undergoing resection for CRLM between 2008 and 2012 at 4
specialty hepatobiliary centers in Canada (N = 740) were stratified by CRS and
analyzed in Kaplan-Meier survival curves. Primary outcome of overall survival
(OS) and secondary outcome of recurrence-free survival (RFS). Multivariate Cox
regression compared CRS to patient factors. RESULTS: Median OS not reached (>60
months), median RFS 16 months. Original CRS strata was a significant (p < 0.001)
predictor of both OS (5-year OS: 0; 75%, 1; 71%, 2; 57%, 3; 57%, 4; 46%) and RFS
(5-year RFS: 0; 39%, 1; 33%, 2; 21%, 3; 21%, 4; 8%). The presence of extrahepatic
colorectal metastatic disease increased recurrence risk (RFS hazard ratio of 1.32
(1.06-1.65)), and the use of intraoperative portal pedicle clamping reduced
recurrence risk (RFS hazard ratio of 0.78 (0.61-0.99)). CONCLUSIONS: The CRS
remains a relevant tool for predicting long-term outcomes for patients undergoing
resection of CRLM. Additional factors such as the presence of extrahepatic
colorectal metastatic disease and the use of intraoperative portal pedicle
clamping may improve the prognostic power of the CRS.
PMID- 28495436
TI - Factors relevant to persistent upper abdominal pain after cholecystectomy.
AB - BACKGROUND: Cholecystectomy is a routine procedure for treatment of upper
abdominal pain (UAP) and other atypical symptoms associated with gallstones. UAP,
however, persists in some cases postoperatively. The present study was to
identify the risk factors relevant to persistent UAP after cholecystectomy.
METHODS: 1714 symptomatic patients undergoing cholecystectomy for gallstones were
enrolled. All the patients were asked to complete a biliary symptom
questionnaire. The risk factors for persistent postcholecystectomy UAP and
features related to sustained relief of postcholecystectomy UAP were evaluated.
RESULTS: 172 (10%) patients complained UAP after cholecystectomy. In multivariate
analysis, female gender, preoperative UAP occurring >24h before admission, and
each episode of UAP >30min were independently associated with persistent
postoperative UAP (all p < 0.05). 132 (76.7%) patients reported sustained relief
of postcholecystectomy UAP, the causes of which remained unknown but were
attributed to functional postcholecystectomy syndrome. Shorter duration of
preoperative UAP (occurring within 24 h before admission), less frequency of
postoperative UAP (<=1 episode per day) and administration of choleretic
medications were independently associated with postoperative UAP relief (all p <
0.05). CONCLUSION: Females with longer historical and more frequent preoperative
UAP are more likely to develop postcholecystectomy UAP. Choleretic medications
are effective in relieving postoperative UAP.
PMID- 28495437
TI - Case-controlled study comparing peri-operative and cancer-related outcomes after
major hepatectomy and parenchymal sparing hepatectomy for metastatic colorectal
cancer.
AB - INTRODUCTION: Liver resection is potentially curative in selected patients with
colorectal liver metastases (CLM). There has been a trend towards parenchyma
sparing hepatectomy (PSH) rather than major hepatectomy (MH) due to lower
perioperative morbidity. Although data from retrospective series suggest that
long-term survival after PSM are similar to MH, these reports may be subject to
selection bias. The aim of this study was to compare outcomes of PSH and MH in a
case-controlled study. PATIENTS AND METHODS: 917 consecutive patients who
underwent liver resection for CLM during 2000-2010 were identified from a
prospective database. 238 patients who underwent PSH were case-matched with 238
patients who had MH, for age, gender, tumour number, maximum tumour diameter,
primary Dukes' stage, synchronicity and chemotherapy status using a propensity
scoring system. Peri-operative outcomes, recurrence and long-term survival were
compared. RESULTS: Fewer PSH patients received peri-operative blood transfusions
(p < 0.0001). MH patients had greater incidence of complications (p = 0.04),
grade III/IV complications (p = 0.01) and 90-day mortality (p = 0.03). Hospital
stay was greater in the MH group (p = 0.04). There was no difference in
overall/disease-free survival. CONCLUSION: Patients with resectable CLM should be
offered PSH if technically feasible. PSH is safer than MH without compromising
long-term survival.
PMID- 28495438
TI - African Americans have a lower prevalence of portal vein thrombosis at the time
of liver transplantation.
AB - BACKGROUND: Perioperative vascular thrombotic events in patients undergoing liver
transplantation (LT) are associated with significant morbidity and mortality.
METHODS: In this retrospective UNOS database analysis, we evaluated the
prevalence of portal vein thrombosis (PVT) and factors contributing to PVT
development in different ethnic groups. RESULTS: Of the 47 953 LT performed
between 2002 and 2015, we identified 3642 cases of PVT. African Americans (AA)
had a significantly lower prevalence of PVT compared to other ethnic groups (p =
0.0001). Multivariable regression analysis confirmed that AA were less likely
than other ethnicities to have PVT (OR = 0.6). AA cohort was more likely to have
infectious or autoimmune causes of liver failure (OR = 1.6, 1.7 respectively) as
well as higher creatinine and INR compared to other groups (OR = 1.6, 1.3
respectively). AA's were less likely to have encephalopathy, ascites, or variceal
bleeding, which might indicate lower portal pressures. AA's were listed for LT
later than other ethnicities and had both a lower functional status and higher
MELD score at the time of registration. DISCUSSION: AA's had a significantly
lower prevalence of preoperative PVT despite having a greater number of factors
predisposing to thrombosis. This predisposition should be considered before
instituting perioperative antithrombotic therapy.
PMID- 28495439
TI - The impact of expanded indications on short-term outcomes for resection of
malignant tumours of the liver over a 30 year period.
AB - BACKGROUND: There are two philosophical approaches to planning liver resection
for malignancy: one strives towards zero postoperative mortality by stringent
selection of candidates, thus inherently limiting patients selected; the other,
accepts a low yet definite postoperative mortality rate, and offers surgery to
all those with potential gain in survival. The aim of this study was to
retrospectively analyse an alternative and evolving strategy, and its impact on
short-term outcomes. METHOD: 3118 consecutive hepatectomies performed in 2627
patients over 3 decades (1980-2011) were analysed. Patient demographics, tumour
characteristics, operative details, and postoperative outcomes were analysed.
RESULTS: 1528 patients (58%) were male. Colorectal liver metastases (1221
patients, 47%) and hepatocellular carcinoma (584 patients, 22%) were the most
common diagnoses. Anatomical resections were performed in 2045 (66%), some form
of vascular clamping was used in 2385 (72%), and blood transfusion was required
in 1130 (36%) patients. Use of preoperative techniques to increase feasibility
and safety of complex liver resections allowed expansion of indications to
include sicker patients with larger tumours in the later period of the study.
Overall morbidity and mortality rates were 31% and 3% respectively. During the
first vs. second half of the study period the postoperative morbidity and
mortality were 19% vs. 36% (p < 0.001) and 2% vs. 4% (p = 0.006) respectively.
CONCLUSION: With increasing experience, more patients were accepted for complex
hepatectomies. However, there was a definite yet contained increase in
postoperative morbidity and mortality.
PMID- 28495441
TI - Ventriculo-caval Shunt Migration.
PMID- 28495440
TI - Corrigendum to 'Live birth derived from oocyte spindle transfer to prevent
mitochondrial disease' [Reproductive BioMedicine Online 34 (2017) 361-368].
PMID- 28495442
TI - Validation of plastic scintillation detectors for applications in low-dose-rate
brachytherapy.
AB - PURPOSE: To develop a plastic scintillation detector (PSD) capable of accurately
measuring dose around a low-dose-rate (LDR) iodine-125 (125I) radioactive seed as
a first step toward in vivo dosimetry for prostate LDR brachytherapy. METHODS:
Using a GEANT4 based Monte Carlo code, photon energy distribution at any position
around a realistic 125I source model was obtained. This energy distribution was
convolved with the expected energy response from a plastic scintillator and
dosimetry accuracy was evaluated. A PSD was constructed and validated in a water
phantom for the entire range of clinically relevant positions around an 125I
radioactive seed. RESULTS: The effect of energy dependence on dosimetry accuracy
was shown to be limited, with a maximum relative difference of 1.2% from the
calibration condition. A sophisticated approach to account for the energy
dependence of PSDs is, therefore, not required if the detector is calibrated
using the same model of radioactive seed or a geometrically similar one. The
measurements were in good agreement with theoretical models for the entire
clinical range. CONCLUSIONS: This study shows that PSDs can be used for accurate
dosimetry in real time around a single 125I seed used in LDR prostate
brachytherapy and is promising for clinical applications.
PMID- 28495443
TI - Dose-volume correlation of cumulative vaginal doses and late toxicity after
adjuvant external radiation and brachytherapy for cervical cancer.
AB - PURPOSE: To investigate dose-response relationship between vaginal doses and long
term morbidity. METHODS AND MATERIALS: Patients receiving adjuvant pelvic (chemo)
radiation and brachytherapy for cervical cancer from January 2011 to December
2014 were included. Baseline vaginal length was determined clinically and from
imaging at BT planning. Dose points were defined along mucosa and at 5 mm depth
at 12, 3, 6, and 9 'o' clock positions at every 2 cm from apex to introitus.
Cumulative equivalent doses in 2 Gy were calculated. Vaginal stenosis was
reported in reference to baseline length according to CTCAE version 3.0. Receiver
operator characteristics curve was used to identify dose thresholds for
univariate and multivariate analysis. RESULTS: Overall, 78 women with median age
of 49 (32-71) years were included. The median dose at vaginal apex mucosa and 5
mm depth was 118 Gy3 (78-198) and 81 Gy3 (70-149) respectively. At median follow
up of 36 (18-60) months, vaginal stenosis >=25%, and grade >= II telangiectasia
was observed in 33.3% and 45.7%, respectively. On receiver operator
characteristics analysis, apical mucosal dose >142 Gy3 and recto-vaginal point
dose >86 Gy3 predicted for stenosis on univariate (p = 0.02, p = 0.06) and
multivariate analysis (p = 0.04). The probability of stenosis increased from 32%
at 70 Gy3, 38% at 80 Gy3, and 45% at 90 Gy3 rectovaginal point dose. No
correlation was observed between vaginal doses and telangiectasia and vaginal
stenosis and sexual quality of life. CONCLUSION: Vaginal apex mucosal dose >142
Gy3 independently predicts for vaginal stenosis.
PMID- 28495444
TI - Comparing the RTOG/EORTC and LENT-SOMA scoring systems for the evaluation of late
skin toxicity after 125I seed brachytherapy for parotid gland cancer.
AB - PURPOSE: The Radiation Therapy Oncology Group (RTOG) and Late Effects Normal
Tissue Task Force-Subjective, Objective, Management and Analytic (LENT-SOMA)
scoring systems were compared for grading late skin effects after iodine-125 seed
brachytherapy in parotid gland cancer patients. METHODS AND MATERIALS: A total of
109 patients diagnosed with parotid gland carcinoma were treated postoperatively
with iodine-125 seed brachytherapy at a dose of 100-120 Gy. After 6-24 months of
followup, telangiectasia, skin pigmentation, atrophy, fibrosis, and ulceration
were scored according to both RTOG and LENT-SOMA scale criteria. The strength of
correlation between the scores and the interobserver variability were calculated.
RESULTS: Of 109 patients, 22.9% had telangiectasia; 78.9%, pigmentation; 28.4%,
fibrosis; 4.6%, edema; 0.9%, ulceration; 37.6%, retraction and/or atrophy; 22.9%,
sensation change; and 11%, scaliness and/or roughness. Compared with RTOG, LENT
SOMA criteria resulted in the upgrading of pigmentation in 17% of cases, the
downgrading of all instances of telangiectasia and the downgrading of one
instance of Grade 4 ulceration to Grade 3. Between the two scales, fibrosis and
atrophy correlated well (Spearman rho, 0.992, 0.986). An additional 229 side
effects were observed using LENT-SOMA criteria. CONCLUSIONS: The LENT-SOMA scale
was more accurate than the RTOG scale for the evaluation of late skin and
subcutaneous toxicity. The downgrading of telangiectasia and upgrading of
pigmentation with the LENT-SOMA scale reflected the patients' conditions better
than the scores obtained with the RTOG scale. The assessment of fibrosis and
atrophy correlated well between the two scales. The use of the sum of the
individual scores of the LENT-SOMA is therefore advocated. The addition of
decreased sweating and the removal of the alopecia (scalp) metric should be
considered to standardize the reporting of late radiation morbidity.
PMID- 28495445
TI - Preservation of von Willebrand factor multimers and function in patients with an
EVAHEART centrifugal-type, continuous-flow left ventricular assist device.
PMID- 28495446
TI - Mechanism of HRP-catalyzed nitrite oxidation by H2O2 revisited: Effect of
nitroxides on enzyme inactivation and its catalytic activity.
AB - The peroxidative activity of horseradish peroxidase (HRP) undergoes progressive
inactivation while catalyzing the oxidation of nitrite by H2O2. The extent of
inactivation increases as the pH increases, [nitrite] decreases or [H2O2]
increases, and is accompanied by a loss of the Soret peak of HRP along with
yellow-greenish coloration of the solution. HRP-catalyzed nitrite oxidation by
H2O2 involves not only the formation of compounds I and II as transient heme
species, but also compound III, all of which in turn, oxidize nitrite yielding
*NO2. The rate constant of nitrite oxidation by compound III is at least 10-fold
higher than that by compound II, which is also reducible by *NO2 where its
reduction by nitrite is the rate-determining step of the catalytic cycle. The
extent of the loss of the Soret peak of HRP is lower than the loss of its
peroxidative activity implying that deterioration of the heme moiety leading to
iron release only partially contributes toward heme inactivation. Cyclic stable
nitroxide radicals, such as 2,2,6,6-tetramethyl-piperidine-N-oxyl (TPO), 4-OH-TPO
and 4-NH2-TPO at uM concentrations detoxify *NO2 thus protecting HRP against
inactivation mediated by this radical. Hence, HRP inactivation proceeds via
nitration of the porphyrin ring most probably through compound I reaction with
*NO2, which partially leads to deterioration of the heme moiety. The nitroxide
acts catalytically since its oxidation by *NO2 yields the respective oxoammonium
cation, which is readily reduced back to the nitroxide by H2O2, superoxide ion
radical, and nitrite. In addition, the nitroxide catalytically inhibits tyrosine
nitration mediated by HRP/H2O2/nitrite reactions system as it efficiently
competes with tyrosyl radical for *NO2. The inhibition by nitroxides of tyrosine
nitration is demonstrated also in the case of microperoxidase (MP-11) and
cytochrome c revealing an additional role played by nitroxide antioxidants.
PMID- 28495447
TI - Characterization of gene expression associated with the adaptation of the
nematode C. elegans to hypoxia and reoxygenation stress reveals an unexpected
function of the neuroglobin GLB-5 in innate immunity.
AB - Oxygen (O2) is a double-edged sword to cells, for while it is vital for energy
production in all aerobic animals and insufficient O2 (hypoxia) can lead to cell
death, the reoxygenation of hypoxic tissues may trigger the generation of
reactive oxygen species (ROS) that can destroy any biological molecule. Indeed,
both hypoxia and hypoxia-reoxygenation (H/R) stress are harmful, and may play a
critical role in the pathophysiology of many human diseases, such as myocardial
ischemia and stroke. Therefore, understanding how animals adapt to hypoxia and
H/R stress is critical for developing better treatments for these diseases.
Previous studies showed that the neuroglobin GLB-5(Haw) is essential for the fast
recovery of the nematode Caenorhabditis elegans (C. elegans) from H/R stress.
Here, we characterize the changes in neuronal gene expression during the
adaptation of worms to hypoxia and recovery from H/R stress. Our analysis shows
that innate immunity genes are differentially expressed during both adaptation to
hypoxia and recovery from H/R stress. Moreover, we reveal that the prolyl
hydroxylase EGL-9, a known regulator of both adaptation to hypoxia and the innate
immune response, inhibits the fast recovery from H/R stress through its activity
in the O2-sensing neurons AQR, PQR, and URX. Finally, we show that GLB-5(Haw)
acts in AQR, PQR, and URX to increase the tolerance of worms to Pseudomonas
aeruginosa pathogenesis. Together, our studies suggest that innate immunity and
recovery from H/R stress are regulated by overlapping signaling pathways.
PMID- 28495449
TI - Peripheral circulatory disorders in essential thrombocythemia.
AB - A significant number of patients with essential thrombocythemia (ET) complain of
symptoms including distal parts of the extremities (e.g., paresthesias or
Raynaud's phenomenon). The aim of the present study was to examine peripheral
circulation in the upper extremities of individuals with ET. The study included
45 ET patients and 30 control subjects. All participants were subjected to
thermography, photoplethysmography, impedance plethysmography, and applanation
tonometry pulse wave analysis. The patients with ET differed significantly from
the control subjects in terms of 3rd finger skin temperature (mean 31.04 vs.
32.45 degrees C), skin temperature gradient (mean 1.82 vs. 0.11 degrees C),
photoplethysmographic amplitude (median 0.25 vs. 0.74%), and pulse waveform in
the radial artery (more frequent occurrence of type B waveform). Pulse wave
parameters correlated with the skin temperature gradient. The study findings
imply the altered regulation of peripheral circulation in ET, including a
decreased flow and an increased resistance.
PMID- 28495448
TI - Nrf2 in keratinocytes modulates UVB-induced DNA damage and apoptosis in
melanocytes through MAPK signaling.
AB - Responses of melanocytes (MC) to ultraviolet (UV) irradiation can be influenced
by their neighbouring keratinocytes (KC). We investigated the role of Nrf2 in
regulating paracrine effects of KC on UVB-induced MC responses through
phosphorylation of MAPKs in association with oxidative stress in primary human MC
cocultured with primary human KC using a transwell co-culture system and small
interfering RNA-mediated silencing of Nrf2 (siNrf2). The mechanisms by which Nrf2
modulated paracrine factors including alpha-melanocyte-stimulating hormone (alpha
MSH) and paracrine effects of KC on UVB-mediated apoptosis were also assessed.
Our findings showed that co-culture of MC with siNrf2-transfected KC enhanced UVB
mediated cyclobutane pyrimidine dimer (CPD) formation, apoptosis and oxidant
formation, together with phosphorylation of ERK, JNK and p38 in MC. Treatment of
MC with conditioned medium (CM) from Nrf2-depleted KC also increased UVB-mediated
MC damage, suggesting that KC modulated UVB-mediated MC responses via paracrine
effects. Additionally, depletion of Nrf2 in KC suppressed UVB-induced alpha-MSH
levels as early as 30min post-irradiation, although pretreatment with N
acetylcysteine (NAC) elevated its levels in CM from siNrf2-transfected KC.
Furthermore, NAC reversed the effect of CM from Nrf2-depleted KC on UVB-induced
apoptosis and inflammatory response in MC. Our study demonstrates for the first
time that KC provided a rescue effect on UVB-mediated MC damage, although
depletion of Nrf2 in KC reversed its protective effects on MC in a paracrine
fashion in association with elevation of ROS levels and activation of MAPK
pathways in MC. Nrf2 may indirectly regulate the paracrine effects of KC probably
by affecting levels of the paracrine factor alpha-MSH via a ROS-dependent
mechanism.
PMID- 28495450
TI - Rho guanine nucleotide exchange factor (RGNEF) is a prosurvival factor under
stress conditions.
AB - Rho guanine nucleotide exchange factor (RGNEF) is a 190kDa RNA binding protein
(RBP) that also contains a Dbl/PH domain capable of RhoA activation. Consistent
with a key role in the pathogenesis of amyotrophic lateral sclerosis (ALS), RGNEF
forms pathological neuronal cytoplasmic inclusions in degenerating spinal motor
neurons. To further understand the role of RGNEF in the stress response, we first
observed that the expression of RGNEF is upregulated in murine spinal motor
neurons following distal sciatic nerve injury. Secondly, in response to in vitro
cellular stress (500MUM sodium arsenite for 1h; or 400mM sorbitol 1 hour
exposure; as an oxidative or osmotic stress, respectively), we observed a
significant survival benefit in RGNEF-transfected HEK293T cells. Using deletion
constructs, we found that the NH2-terminus domain is essential for this
protective effect. Interestingly, we observed that under stress conditions RGNEF
associates with Staufen1 positive granules but not TIA-1-positive stress
granules. These findings support the hypothesis that RGNEF plays a critical role
both in RNA homeostasis and in the response to cell stress.
PMID- 28495451
TI - Comparison of Image Quality and Diagnostic Performance of Cone-Beam CT during
Drug-Eluting Embolic Transarterial Chemoembolization and Multidetector CT in the
Detection of Hepatocellular Carcinoma.
AB - PURPOSE: To compare image quality and diagnostic performance of cone-beam
computed tomography (CT) and multidetector CT in the detection of hypervascular
hepatocellular carcinoma (HCC) in patients with cirrhosis undergoing
transarterial chemoembolization with drug-eluting embolic agents. MATERIALS AND
METHODS: Fifty-five consecutive patients referred for chemoembolization of
hypervascular HCC were prospectively enrolled. Imaging included preprocedural
multidetector CT within 1 month before planned treatment, intraprocedural cone
beam CT, and 1-month follow-up multidetector CT. Analysis of image quality was
performed with calculations of lesion-to-liver contrast-to-noise ratio (LLCNR)
and lesion-to-liver signal-to-noise-ratio (LLSNR). One-month follow-up
multidetector CT was considered the reference standard for the detection of HCC
nodules. RESULTS: Median LLCNR values were 3.94 (95% confidence interval [CI],
3.06-5.05) for preprocedural multidetector CT and 6.90 (95% CI, 5.17-7.77) for
intraprocedural cone-beam CT (P < .0001). Median LLSNR values were 11.53 (95% CI,
9.51-12.44) for preprocedural multidetector CT and 9.36 (95% CI, 8.12-10.39) for
intraprocedural cone-beam CT (P < .0104). Preprocedural multidetector CT detected
115 hypervascular nodules with typical HCC behavior, and cone-beam CT detected 15
additional hypervascular nodules that were also visible on 1-month follow-up
multidetector CT. CONCLUSIONS: Cone-beam CT has a significantly higher diagnostic
performance compared with preprocedural multidetector CT in the detection of HCCs
and can influence management of patients with cirrhosis by identifying
particularly aggressive tumors.
PMID- 28495452
TI - Society of Interventional Radiology Position Statement on Parental Leave.
PMID- 28495453
TI - Relative Initial Weight Is Associated with Improved Survival without Altering
Tumor Latency in a Translational Rat Model of Diethylnitrosamine-Induced
Hepatocellular Carcinoma and Transarterial Embolization.
AB - PURPOSE: To test the hypotheses that (i) heavier rats demonstrate improved
survival with diminished fibrosis in a diethylnitrosamine (DEN)-induced model of
hepatocellular carcinoma (HCC) and (ii) transarterial embolization via femoral
artery access decreases procedure times versus carotid access. MATERIALS AND
METHODS: One hundred thirty-eight male Wistar rats ingested 0.01% DEN in water ad
libitum for 12 weeks. T2-weighted magnetic resonance imaging was used for tumor
surveillance. Rats underwent selective embolization of >= 5 mm tumors via carotid
or femoral artery catheterization under fluoroscopic guidance. Rats were
retrospectively categorized into 3 groups by initial weight (< 300, 300-400, >
400 g) for analyses of survival, tumor latency, and fibrosis. Access site was
compared relative to procedural success, mortality, and time. RESULTS: No
significant differences in tumor latency were related to weight group (P = .310).
Rats weighing < 300 g had shorter survival than both heavier groups (mean, 88 vs
108 d; P < .0001), and more severe fibrosis (< 300 g median, 4.0; 300-400 g
median, 1.5; > 400 g median, 1.0; P = .015). No significant difference was found
in periprocedural mortality based on access site; however, procedure times were
shorter via femoral approach (mean, 71 +/- 23 vs 127 +/- 24 min; P < .0001).
CONCLUSIONS: Greater initial body weight resulted in improved survival without
prolonged tumor latency for rats with DEN-induced HCCs and was associated with
less severe fibrosis. A femoral approach for embolization resulted in decreased
procedure time. These modifications provide a translational animal model of HCC
and transarterial embolization that may be suited for short-term survival
studies.
PMID- 28495454
TI - Intratesticular and incisional line infiltration with ropivacaine for castration
in medetomidine-butorphanol-midazolam sedated dogs.
AB - OBJECTIVE: To evaluate whether intratesticular and incisional ropivacaine
infiltration produces sufficient intra- and postoperative analgesia for
castrating dogs under sedation. STUDY DESIGN: Randomized, blinded, controlled
clinical study. ANIMALS: Twenty-three healthy dogs weighing 5.8-35.6 kg admitted
for castration. METHODS: Dogs were sedated with medetomidine (0.01 mg kg-1),
butorphanol (0.2 mg kg-1) and midazolam (0.2 mg kg-1) intramuscularly, and were
randomly assigned to group R, 0.2-0.4 mL kg-1 of ropivacaine 0.5%, or group S, an
equivalent volume of saline injected intratesticularly and along the incision
line. If persistent motion was observed during surgery, sedation was considered
to be insufficient and general anaesthesia was induced. Carprofen 2.2 mg kg-1 was
administered postoperatively. Pain was evaluated in all dogs before sedation and
postoperatively following atipamezole administration at 1, 2, 4, 8 and 24 hours
using an interactive visual analogue scale (IVAS; 0-100), the Glasgow composite
pain scale-short form (CMPS-SF; 0-24), and a mechanical algometer. Methadone 0.3
mg kg-1 was administered intravenously to dogs if IVAS >30 or CMPS-SF >4.
RESULTS: There was no significant difference between groups for the number of
dogs administered general anaesthesia. The time from the beginning of surgery to
induction of general anaesthesia was significantly shorter [median (range)] in
group S [6 (3-25) minutes] than in group R [56 (36-76) minutes]. At 8 hours IVAS
was significantly higher in group S (14 +/- 10) than in group R (6 +/- 4).
CONCLUSIONS AND CLINICAL RELEVANCE: Intratesticular and incisional ropivacaine
infiltration delayed the time to anaesthesia induction, and provided analgesia
after castration performed under deep sedation in dogs. Intratesticular local
anaesthesia can be an important part of the anaesthetic plan for castration.
PMID- 28495455
TI - Increased Left Ventricular Diastolic Stiffness Is Associated With Heart Failure
Symptoms in Aortic Stenosis Patients With Preserved Ejection Fraction.
AB - BACKGROUND: Clinical risk factors associated with heart failure (HF) symptoms in
aortic stenosis (AS) patients with preserved ejection fraction (EF) have not been
fully identified. We hypothesized that left ventricular (LV) diastolic stiffness
is associated with HF symptoms in patients with AS. METHODS AND RESULTS: We
retrospectively evaluated 275 patients with at least moderate AS (aortic valve
area <1.5 cm2) and preserved EF (>=50%). LV diastolic stiffness was evaluated
with the use of echocardiographic parameters, diastolic wall strain (DWS, a
measure of LV wall stiffness), and KLV (a marker of LV chamber stiffness). There
were 69 patients with HF. Patients with HF were older, were more likely to be
African American, had a higher body mass index, and had more hypertension and
coronary artery disease (P < .05 for all). Aortic valve area index and mean
pressure gradient across the aortic valve were not different between patients
with and without HF. Despite similar echocardiographic parameters of AS severity,
patients with HF had stiffer LV (DWS 0.21 +/- 0.06 vs 0.25 +/- 0.06 [P < .01],
KLV 0.17 +/- 0.11 vs 0.13 +/- 0.08 [P < .01]). Logistic regression analyses
revealed that after adjusting for age, race, body mass index, history of
hypertension, and coronary artery disease, LV diastolic stiffness parameters
remained significantly associated with HF symptoms. CONCLUSIONS: LV diastolic
stiffness is independently associated with HF in AS patients with preserved EF.
PMID- 28495457
TI - Effects of arsenic on adipocyte metabolism: Is arsenic an obesogen?
AB - The environmental obesogen model proposes that in addition to a high-calorie diet
and diminished physical activity, other factors such as environmental pollutants
and chemicals are involved in the development of obesity. Although arsenic has
been recognized as a risk factor for Type 2 Diabetes with a specific mechanism,
it is still uncertain whether arsenic is also an obesogen. The impairment of
white adipose tissue (WAT) metabolism is crucial in the onset of obesity, and
distinct studies have evaluated the effects of arsenic on it, however only in
some of them for obesity-related purposes. Thus, the known effects of arsenic on
WAT/adipocytes were integrated based on the diverse metabolic and physiological
processes that occur in WAT and are altered in obesity, specifically: adipocyte
growth, adipokine secretion, lipid metabolism, and glucose metabolism. The
currently available information suggests that arsenic can negatively affect WAT
metabolism, resulting in arsenic being a potential obesogen.
PMID- 28495456
TI - Crosstalk between STAT5 activation and PI3K/AKT functions in normal and
transformed mammary epithelial cells.
AB - Janus kinases (JAKs) and signal transducers and activators of transcription
(STATs) have been shown to function downstream of several peptide hormones and
cytokines that are required for postnatal development and secretory function of
the mammary gland. As part of an extended network, these signal transducers can
engage in crosstalk with other pathways to facilitate synergistic, and sometimes
antagonistic, actions of different growth factors. Specifically, signaling
through the JAK2/STAT5 cascade has been demonstrated to be indispensable for the
specification, proliferation, differentiation, and survival of secretory mammary
epithelial cells. Following a concise description of major cellular programs in
mammary gland development and the role of growth factors that rely on JAK/STAT
signaling to orchestrate these programs, this review highlights the significance
of active STAT5 and its crosstalk with the PI3 kinase and AKT1 for mediating the
proliferation of alveolar progenitors and survival of their functionally
differentiated descendants in the mammary gland. Based on its ability to provide
self-sufficiency in growth signals that are also capable of overriding intrinsic
cell death programs, persistently active STAT5 can serve as a potent oncoprotein
that contributes to the genesis of breast cancer. Recent experimental evidence
demonstrated that, similar to normal developmental programs, oncogenic functions
of STAT5 rely on molecular crosstalk with PI3K/AKT signaling for the initiation,
and in some instances the progression, of breast cancer. The multitude by which
STATs can interact with individual mediators of the PI3K/AKT signaling cascade
may provide novel avenues for targeting signaling nodes within molecular networks
that are crucial for the survival of cancer cells.
PMID- 28495458
TI - Demonstration of a bronchobiliary fistula using magnetic resonance image with
hepatospecific contrast agent.
AB - Bronchobiliary fistulas are a rare entity of difficult diagnosis. The utility of
magnetic resonance image (MRI) with hepatospecific contrast agents to demonstrate
such condition is seldom described in the literature. This case reports a patient
with pulmonary infection with a past history of hepatic surgery for hydatid
disease in whom the presence of bile in the sputum rose the suspicious of a
bronchobiliary fistula. MRI with hepatospecific contrast agents showed the
communication between the biliary and bronchial tree and provided anatomic data
to allow a therapeutic approach.
PMID- 28495459
TI - Anaphylactic shock secondary to ruptured hydatid cyst of liver into the pleural
cavity.
PMID- 28495460
TI - Dual-energy computed tomography for the detection of focal liver lesions.
AB - OBJECTIVE: To qualitatively and quantitatively explore the spectral study of
focal liver lesions, comparing it with the usual polychromatic assessment with
single-energy computed tomography. MATERIAL AND METHODS: We prospectively studied
50 patients with at least one focal liver lesion who were referred for abdominal
multidetector computed tomography with intravenous contrast material. The portal
phase was acquired with dual energy sources. The density of the lesions and of
the surrounding liver parenchyma was measured both in the baseline polychromatic
acquisition and in the posterior monochromatic reconstructions at 40 keV, 70 keV,
and 140 keV. Spectral curves were traced and the dual-energy indices and contrast
to-noise ratio were calculated. Lastly, the quality of the images and the
detectability of the lesions were assessed qualitatively. RESULTS: Densitometric
differences between the different types of lesions (avascular and vascularized)
and the liver were greater at low energy levels (left side of the spectral curve)
than in the polychromatic evaluation. In the subjective assessment, the 40keV
energy level had the greatest lesion detectability. CONCLUSIONS: Monochromatic
spectral study with dual-energy computed tomography provides better lesion
detectability at 40keV compared to that provided by the ordinary polychromatic
evaluation.
PMID- 28495461
TI - [Placental metastasis of breast adenocarcinoma].
PMID- 28495462
TI - Birth preference in women undergoing treatment for childbirth fear: A randomised
controlled trial.
AB - BACKGROUND: Childbirth fear is the most common underlying reason for requesting a
caesarean section without medical reason. The aim of this randomised controlled
study was to investigate birth preferences in women undergoing treatment for
childbirth fear, and to investigate birth experience and satisfaction with the
allocated treatment. METHODS: Pregnant women classified with childbirth fear
(>=60 on the Fear Of Birth Scale) (n=258) were recruited at one university
hospital and two regional hospitals over one year. The participants were
randomised (1:1) to intervention (Internet-based Cognitive Behaviour Therapy
(ICBT)) (n=127) or standard care (face-to-face counselling) (n=131). Data were
collected by questionnaires in pregnancy week 20-25 (baseline), week 36 and two
months after birth. RESULTS: Caesarean section preference decreased from 34% to
12% in the ICBT group and from 24% to 20% in the counselling group. Two months
after birth, the preference for caesarean increased to 20% in the ICBT group and
to 29% in the counselling group, and there was no statistically significant
change over time. Women in the ICBT group were less satisfied with the treatment
(OR 4.5). The treatment had no impact on or worsened their childbirth fear (OR
5.5). There were no differences between the groups regarding birth experience.
CONCLUSION: Women's birth preferences fluctuated over the course of pregnancy and
after birth regardless of treatment method. Women felt their fear was reduced and
were more satisfied with face-to-face counselling compared to ICBT. A higher
percentage were lost to follow-up in ICBT group suggesting a need for further
research.
PMID- 28495463
TI - Development of an animal model of progressive vaccinia in nu/nu mice and the use
of bioluminescence imaging for assessment of the efficacy of monoclonal
antibodies against vaccinial B5 and L1 proteins.
AB - Bioluminescence imaging (BLI) was used to follow dissemination of recombinant
vaccinia virus (VACV) expressing luciferase (IHD-J-Luc) in BALB/c nu/nu mice
treated post-challenge with monoclonal antibodies (MAbs) against L1 and B5 VACV
proteins in a model of Progressive Vaccinia (PV). Areas Under the flux Curve
(AUC) were calculated for viral loads in multiple organs in individual mice.
Following scarification with 105 pfu, IHD-J-Luc VACV undergoes fast replication
at the injection site and disseminates rapidly to the inguinal lymph nodes
followed by spleen, liver, and axillary lymph nodes within 2-3 days and before
primary lesions are visible at the site of scarification. Extension of survival
in nude mice treated with a combination of anti-B5 and anti-L1 MAbs 24 h post
challenge correlated with a significant reduction in viral load at the site of
scarification and delayed systemic dissemination. Nude mice reconstituted with
104 T cells prior to challenge with IHD-J-Luc, and treated with MAbs post
challenge, survived infection, cleared the virus from all organs and
scarification site, and developed anti-VACV IgG and VACV-specific polyfunctional
CD8+ T cells that co-expressed the degranulation marker CD107a, and IFNgamma and
TNFalpha cytokines. All T cell reconstituted mice survived intranasal re
challenge with IHD-J-Luc (104 pfu) two months after the primary infection. Thus,
using BLI to monitor VACV replication in a PV model, we showed that anti-VACV
MAbs administered post challenge extended survival of nude mice and protected T
cell reconstituted nude mice from lethality by reducing replication at the site
of scarification and systemic dissemination of VACV.
PMID- 28495464
TI - MicroRNA-21 via Dysregulation of WW Domain-Containing Protein 1 Regulate Atrial
Fibrosis in Atrial Fibrillation.
AB - BACKGROUND: microRNAs (miRs) have been reported to regulate cell biological
functions. To explore the underlying mechanism of miR-21 involvement in patients
with atrial fibrosis and atrial fibrillation (AF). METHODS: In total, 49 patients
(24 AF, sinus rhythm 25) aged 33-68 years old, including heart valve replacement
surgery and cardiac catheterisation. The pathological changes and collagen
depositions was analysed by Masson's Trichrome Staining. miR-21, TGF-beta1,
Smad2, p-Smad2, WWP-1, collagen I and collagen III expression were analysed by
Western blotting, qRT-PCR, miR one step qRT-PCR, respectively. Treatment human
cardiac fibroblasts with TGF-beta1, qRT-PCR and Western blotting to find changes
in miR-21, Smad2 and WWP-1 levels. Transfected human cardiac fibroblasts with miR
21 mimic and miR-21 inhibitor. Finally, cell proliferation ability was assessed
by the MTT assay and flow cytometry. RESULTS: Compared to sinus rhythm (SR)
group, the collagen volume fraction was significantly increased in AF patients.
The levels of the TGF-beta1, collagen I and collagen III were significantly
elevated in AF group. In AF patients, the expression of miR-21 was increased,
while the expression of WWP-1 was decreased. Transfected cardiac fibroblasts with
miR-21 mimic increased miR-21 expression and decreased WWP-1 expression, whereas
miR-21 inhibitor causes the opposite effects. Additionally, we demonstrated that
knockdown miR-21 targeted up-regulation of WWP-1 may suppress cardiac fibroblasts
proliferation. CONCLUSION: These indicated that miR-21 inhibits cardiac
fibroblasts proliferation by inactivating the TGF-beta1/Smad2 signaling pathway
via up-regulation of WWP-1.
PMID- 28495465
TI - The effect of blue-enriched white light on cognitive performances and sleepiness
of night-shift workers: A field study.
AB - INTRODUCTION: Night-shift works are basically accompanied by reduced cognitive
performance, sleepiness, and higher possibility for human error and related
incidents. It is therefore crucial to improve individuals' performance and
alertness in sensitive places like industries' control room with the ultimate
goal of increasing efficiency and reducing the number of possible incidents.
Previous research has indicated that blue light is a critical cue for entraining
circadian rhythm. As a result, the present study was an attempt to investigate
whether blue-enriched white light illumination was a practical strategy to
decrease sleepiness and improve cognitive performance during night shifts.
MARTIAL AND METHODS: The study, which adopted a before-after interventional
design, was conducted among 30 control room staff members of petrochemical
industry. After baseline assessments under existing lighting conditions, every
participant was exposed to two new lighting conditions (namely, 17,000K and 6500K
blue-enriched white light), each lasting for a week. Assessments were conducted
again at the end of these treatments. In order to measure the subjective
sleepiness, Karolinska Sleepiness Scale (KSS) was utilized. Subjects also
performed the Conners' Continuous Performance Test II (CPT-II) and 1-back test in
order to gauge their cognitive performance, and melatonin assessment was carried
out using salivary and Eliza technique. The data was analyzed using two-way
repeated measure ANOVA. RESULTS: The results indicated that, compared to normal
lighting conditions, participants' sleepiness and melatonin rhythm significantly
declined when they were exposed to blue-enriched white light. Furthermore, the
experimental condition had a significant effect on the reduction of working
memory errors. It also decreased omission errors and the reaction time during the
sustained attention task. CONCLUSIONS: Thus, using blue-enriched white light may
be a proper ergonomic strategy for improving performance and alertness,
especially during night, in sensitive environments like control rooms.
PMID- 28495466
TI - Methicillin-resistant Staphylococcus aureus Screening PCR adapted to locally
emerging variants-Evaluation of novel SCCmec primers.
AB - Infections with multi-resistant bacteria, such as Methicillin-resistant
Staphylococcus aureus (MRSA), represent a world-wide health-care problem. The
original MRSA Screening TaqMan PCR was based on the detection of the SCCmec-orfX
junction as described by the group of Huletsky in 2004. In the recent years, this
assay increasingly failed to detect new MRSA variants in swab specimens. In this
work, we analyzed the usefulness of 17 additional SCCmec primers to increase PCR
sensitivity by testing 290 collected samples with negative PCR results and
positive MRSA culture in a retrospective analysis, and 380 samples of the daily
routine diagnostics. Sequencing of the PCR products revealed that locally new
MRSA variants became detectable by nine of these forward primers. Four primers
were solely responsible for the detection of 85.4% (117/123) of the PCR products:
F13 (n=76), F11 (n=6), F14 (n=15) and F25 (n=8). These four primers were
integrated in the Screening PCR and the novel primer collection was validated by
testing 71 MRSA isolates, which covered SCCmec types I to VI, 50 MSSA isolates
and 100 swab specimens. The sensitivity of MRSA Screening PCR increased from 93%
to 98.6% without affecting the detection of the common MRSA strains. Phylogenetic
analysis of the PCR products suggests that the adapted MRSA Screening PCR is able
to detect SCCmec types I-X, including CA- and LA-MRSA variants by the SCCmec
primers F11 and F25.
PMID- 28495467
TI - Mobile Health Technology in Late-Life Mental Illness: A Focused Literature
Review.
AB - OBJECTIVE: In an era of rising geriatric mental health care needs worldwide,
technological advances can help address care needs in a cost-effective fashion.
Our objective in this review was to assess whether mobile health technology, such
as tablets and smartphones, are feasible to use in patients with late-life mental
and cognitive disorders, as well as whether they were generally reliable modes of
mental health/cognitive assessment. METHODS: We performed a focused literature
review of MEDLINE, PsychInfo, and Embase databases, including papers specifically
assessing the implementation of mobile health technologies: electronic tablets
(e.g., iPad), smartphones, and other mobile computerized equipment in older
adults (age >=65 years) diagnosed with or at risk of a mental and/or cognitive
disorder. RESULTS: A total of 2,079 records were assessed, of which 7 papers were
of direct relevance. Studies investigated a broad variety of mobile health
technologies. Almost all examined samples with dementia/cognitive dysfunction or
at risk for those disorders. All studies exclusively examined the use of mobile
health technologies for the assessment of cognitive and or mental illness
symptoms or disorders. None of the studies reported participants having any
difficulties using the mobile health technology assessments and overall
reliability was similar to paper-and-pencil modes of assessment. CONCLUSION:
Overall, mobile health technologies were found to be feasible by patients and had
promising reliability for the assessment of cognitive and mental illness domains
in older adults. Future clinical trials will be necessary to assess whether
portable communication interventions (e.g., symptom tracking) can improve
geriatric mental health outcomes.
PMID- 28495468
TI - Commentary for "Steeper Slope of Age-Related Changes in White Matter
Microstructure and Processing Speed in Bipolar Disorder".
PMID- 28495469
TI - Clock Copying Predicts Mortality in Adult Protective Services Clients.
AB - OBJECTIVE: The objective of this study was to determine if a clock copying task
predicts 18-month mortality in an Adult Protective Services (APS) sample referred
for a decision-making capacity assessment. METHODS: The authors performed a
retrospective medical record review of clients (N = 233) referred by APS for a
decision-making capacity assessment during a 3-year time period. Information
extracted included demographic data and neuropsychological performance on a
battery sensitive to executive function, visuospatial ability, depression,
memory, and general cognition. A Cox proportional hazards models was constructed
to determine the relationship between Executive Clock Drawing Task Part 2 (CLOX2)
performance and survival. RESULTS: Poor clock copying, as measured by CLOX2,
predicted 18-month mortality when covaried for age, education, sex, rural
dwelling status, depression, and general cognition. CONCLUSIONS: Clock copying is
an easily administered visuospatial task that may inform survival in this
vulnerable population.
PMID- 28495471
TI - Quantitative outcome measures for systemic sclerosis-related Microangiopathy -
Reliability of image acquisition in Nailfold Capillaroscopy.
AB - BACKGROUND: Nailfold capillaroscopic parameters hold increasing promise as
outcome measures for clinical trials in systemic sclerosis (SSc). Their inclusion
as outcomes would often naturally require capillaroscopy images to be captured at
several time points during any one study. Our objective was to assess
repeatability of image acquisition (which has been little studied), as well as of
measurement. METHOD: 41 patients (26 with SSc, 15 with primary Raynaud's
phenomenon) and 10 healthy controls returned for repeat high-magnification (300*)
videocapillaroscopy mosaic imaging of 10 digits one week after initial imaging
(as part of a larger study of reliability). Images were assessed in a random
order by an expert blinded observer and 4 outcome measures extracted: (1) overall
image grade and then (where possible) distal vessel locations were marked,
allowing (2) vessel density (across the whole nailfold) to be calculated (3) apex
width measurement and (4) giant vessel count. Intra-rater, intra-visit and intra
rater inter-visit (baseline vs. 1week) reliability were examined in 475 and 392
images respectively. A linear, mixed-effects model was used to estimate variance
components, from which intra-class correlation coefficients (ICCs) were
determined. RESULTS: Intra-visit and inter-visit reliability estimates (ICCs)
were (respectively): overall image grade, 0.97 and 0.90; vessel density, 0.92 and
0.65; mean vessel width, 0.91 and 0.79; presence of giant capillary, 0.68 and
0.56. These estimates were conditional on each parameter being measurable.
CONCLUSION: Within-operator image analysis and acquisition are reproducible.
Quantitative nailfold capillaroscopy, at least with a single observer, provides
reliable outcome measures for clinical studies including randomised controlled
trials.
PMID- 28495472
TI - Matrix-specific distribution and diastereomeric profiles of
hexabromocyclododecane (HBCD) in a multimedia environment: Air, soil, sludge,
sediment, and fish.
AB - Hexabromocyclododecane (HBCD) contamination and its diastereomeric profile were
investigated in a multi-media environment along a river at the local scale in
air, soil, sludge, sediment, and fish samples. The spatial distribution of HBCD
in each matrix showed a different result. The highest concentrations of HBCD in
air and soil were detected near a general industrial complex; in the sediment and
sludge samples, they were detected in the down-stream region (i.e., urban area).
Each matrix showed the specific distribution patterns of HBCD diastereomers,
suggesting continuous inputs of contaminants, different physicochemical
properties, or isomerizations. The particle phases in air, sludge, and fish
matrices were dominated by alpha-HBCD, owing to HBCD's various isomerization
processes and different degradation rate in the environment, and metabolic
capabilities of the fish; in contrast, the sediment and soil matrices were
dominated by gamma-HBCD because of the major composition of the technical
mixtures and the strong adsorption onto solid particles. Based on these results,
the prevalent and matrix-specific distribution of HBCD diastereomers suggested
that more careful consideration should be given to the characteristics of the
matrices and their effects on the potential influence of HBCD at the
diastereomeric level.
PMID- 28495470
TI - Cognitive Effects of Chemotherapy and Cancer-Related Treatments in Older Adults.
AB - Advances in cancer treatment are producing a growing number of cancer survivors;
therefore, issues surrounding quality of life during and following cancer
treatment have become increasingly important. Chemotherapy-related cognitive
impairment (CRCI) is a problem that is commonly reported following the
administration of chemotherapy treatment in patients with cancer. Research
suggests that CRCI can persist for months to years after completing treatment,
which has implications for the trajectory of normal and pathologic cognitive
aging for the growing number of long-term cancer survivors. These problems are
particularly relevant for older individuals, given that cancer is largely a
disease of older age, and the number of patients with cancer who are aged 65
years or older will increase dramatically over the coming decades. This review
will briefly summarize empirical findings related to CRCI, discuss CRCI in older
patients with cancer, propose potential causative hypotheses, and provide a
canonical patient case to illustrate how CRCI presents clinically. Finally,
potential intervention strategies for CRCI will be highlighted and issues to
consider when evaluating older patients with a history of cancer will be
discussed.
PMID- 28495473
TI - Genetic polymorphisms of the P2X7 gene associated with susceptibility to and
prognosis of pulmonary tuberculosis.
AB - In this population-based case control study, we recruited 1601 pulmonary
tuberculosis cases and 1526 healthy controls, aiming to investigate the
association of genetic polymorphisms of the P2X7 gene with the susceptibility to
and prognosis of pulmonary tuberculosis in a Chinese Han population. Five single
nucleotide polymorphisms (SNPs) in the P2X7 gene were genotyped. The odds ratio
(OR) or relative risk (RR) together with 95% confidence interval (CI) were used
to estimated the effect of genetic polymorphisms on the disease. After correction
for multiple comparisons, the SNP rs1718119 remained significant. The allele A of
rs1718119 was related to a reduced risk for all active tuberculosis (OR for each
additional allele A: 0.81, 95% CI: 0.69-0.94) and sputum smear-positive cases (OR
for each additional allele A: 0.78, 95% CI: 0.66-0.93). The effects of these
genetic variations were more evident among smokers. Survival analysis showed a
weak association between rs7958311 and treatment outcome, where each additional
allele A of the SNP rs7958311 contributed to a 59% increase in the probability of
a successful treatment outcome (adjusted RR: 1.59, 95% CI: 1.05-2.40, P=0.028);
but it wasn't significant after the Bonferroni correction. We demonstrated that
genetic variations of the P2X7 gene might be involved in the risk and prognosis
of human tuberculosis.
PMID- 28495474
TI - Late effect of developmental exposure to glycidol on hippocampal neurogenesis in
mice: Loss of parvalbumin-expressing interneurons.
AB - Developmental exposure to glycidol of rats causes axonal injury targeting axon
terminals in dams and transient disruption of late-stage differentiation of
hippocampal neurogenesis, accompanying sustained increase in the number of reelin
producing or calretinin-expressing interneurons in offspring. The molecular
mechanism of disruptive neurogenesis probably targets the newly generating nerve
terminals. We previously found differences between mice and rats in the effects
on hippocampal neurogenesis after developmental exposure to the same neurotoxic
substances. In the present study, we examined the effects and underlying
mechanisms of developmental exposure to glycidol on hippocampal neurogenesis in
mice. Glycidol (800 or 1600ppm) was administered in drinking water to mated
female mice from gestational day 6 to postnatal day 21. Compared to mice drinking
water without glycidol (control), the exposed dams showed axon terminal injury at
both concentrations of glycidol. The offspring of the dams that had received
1600ppm glycidol had fewer parvalbumin (PVALB)+ gamma-aminobutyric acid (GABA)
ergic interneurons and neuron-specific nuclear protein+ postmitotic neurons in
the hilus of the hippocampal dentate gyrus. Thus, exposure of glycidol to adult
mice induced axonal degeneration equivalent to that seen in the rat; however, the
target mechanism for the disruption of hippocampal neurogenesis by developmental
exposure was different from that in rats, with the hilar neuronal population not
affected until adulthood. Considering the role of PVALB+ GABAergic interneurons
in the brain, developmental glycidol exposure in mice may cause a decline in
cognitive function in later life, and involve a different mechanism from that
targeting axon terminals in rats.
PMID- 28495475
TI - Ameliorative effects of Achillea millefolium inflorescences alcoholic extract
against nicotine-induced reproductive failure in rat.
AB - BACKGROUND: Nicotine (Nic) is a major risk factor in the development of
functional disorders of male reproductive system. Achillea millefolium; is highly
regarded for medicinal activities, due to its antioxidant and anti-inflammatory
properties. This study was carried out to evaluate whether Achillea millefolium
(Achm) inflorescences alcoholic extract could serve as a protective agent in male
reproductive male failures during Nic exposure in a rat model. METHODS: Twenty
five adult male Wistar rats were categorized into the five groups. Tests 1 and 3
groups were received Nic at dose levels of 0.2 and 0.4mg/kg BW/day, respectively
by IP injection. Tests 2 and 4 groups were received Nic at the same doses along
with Achm at dose level of 120mg/kg BW/day. The study period took forty-eight
days for all experimental groups. RESULTS: Nic groups showed significant
decreases in tubule differentiation index (TDI), sperm count, motility,
stereological parameters and an increase in dead and abnormal sperms. Moreover,
the reduction in total antioxidant capacity (TAC), superoxide dismutase (SOD)
activity, serum levels of FSH, LH and testosterone, along with increased serum
concentration of LDH were observed in the Nic groups. Total nitrite and
malondealdehyde levels increased and total thiol molecules (TTM) levels decreased
in testicular tissue in the Nic groups. Notably, Achm co-administration caused a
contemporary recovery in above-mentioned parameters. CONCLUSION: Nic exerts major
toxicity in testicular tissue and causes damages in several ways including,
oxidative stress, whilst Achm imposes protective effect against Nic-induced
reproductive failure, which may attribute to its antioxidant capacity.
PMID- 28495476
TI - Studies on diagnostic biomarkers and therapeutic mechanism of Alzheimer's disease
through metabolomics and hippocampal proteomics.
AB - Alzheimer's disease (AD) is the main cause of dementia, but precise diagnosis and
treatment are not sufficient so far. The purpose of this study is to develop
biomarkers and therapeutic targets for diagnosis and better understanding of AD.
As a result, lysophosphatidylcholine and intermediates of sphingolipid metabolism
including sphinganine-1-phosphate, sphingosine-1-phosphate, sphingomyelin, and
sphingosine in plasma were annotated as potential biomarkers by using UPLC-Q-TOF
MS and UHPLC-Q-Exactive-MS. Besides, glutathione S-transferases (GSTs) including
GstA3, Gstm1, Gstm5, Gstm3, Gstk1 and Gstp1 were significantly enhanced in AD
hippocampus by using label free nano-LC-MS/MS. Thus, pathogenesis of AD was
involved with increasing of choline, decreasing of ACh, enhancement of GSTs and
increasing of glutamate which led to oxidative stress and excitotoxity. Effects
of donepezil and a natural medicine were evaluated through metabolomics and
proteomics. In summary, proteomic and metabolomic analysis on constructed AD rat
model were performed through rapid, sensitive and high resolution LC-MS methods
to reveal candidate biomarkers. The data suggested that GSTs have great value as
therapeutic targets. This study provided valuable information for the diagnosis
mechanism and drug discovery of AD.
PMID- 28495477
TI - Quantification of saxitoxin in human blood by ELISA.
AB - Saxitoxin (STX) is a potent marine toxin that causes paralytic shellfish
poisoning (PSP) which can result in significant morbidity and mortality in
humans. Low lethal doses, rapid onset of PSP symptoms, and brief STX half-life in
vivo require sensitive and rapid diagnostic techniques to monitor human
exposures. Our laboratory has validated an enzyme-linked immunosorbent assay
(ELISA) for quantitative detection of STX from 0.020 to 0.80 ng/mL in human whole
blood and from 0.06 to 2.0 ng/mL in dried human blood which is simple, sensitive,
rapid, and cost-effective. To our knowledge, this is the first validated method
for the quantitation of saxitoxin in whole blood. Microsampling devices were used
in sample collection which allows for standardized collection of blood, stable
storage, and cost-efficient shipping. Quality control precision and accuracy were
evaluated over the course of validation and were within 20% of theoretical
concentrations. No detectable background concentrations of STX were found among
fifty whole blood and dried blood convenience samples. Additionally, ten spiked
individual whole blood and dried blood samples were tested for accuracy and
precision and were within 20% of theoretical concentrations. Gonyautoxins 2&3
(GTX2&3) cross-reacted with this ELISA by 21%, but all other structurally related
PSP toxins tested cross-reacted less than two percent. While clinical diagnosis
or treatment of PSP would be unaffected by GTX2&3 cross-reactivity by ELISA, to
accurately quantify individual PSP toxins, these results should be coupled with
high performance liquid chromatography mass spectrometry measurements.
PMID- 28495479
TI - Limited sampling strategies for determining the area under the plasma
concentration-time curve for isoniazid might be a valuable approach for
optimizing treatment in adult patients with tuberculosis.
AB - This study aimed to develop clinically feasible models of limited sampling
strategy (LSS) for estimation of the area under the concentration-time curve
(AUC24h) for isoniazid, that could be applied easily in daily clinical practice
for dosage adjustment in adult patients with tuberculosis. Isoniazid plasma
concentrations (n = 1665) from 185 adult tuberculous patients were used for the
development and validation of LSS models to estimate AUC24h following
administration of the standard 5 mg/kg dose of isoniazid. Population
pharmacokinetic analysis for appropriate estimation of isoniazid pharmacokinetic
parameters was performed in a modelling group (n = 100). The Bayesian estimates
of AUC24h (AUCref) obtained for each individual were used as the dependent
variable in the regression analysis for the development of various LSS models.
The LSS models were validated in a separate cohort (n = 85). Several three and
four time point LSS models were built and tested. Model H (AUC24h = -1.88 + 1.05
* C1 + 0.78 * C2 + 9.44 * C5) and Model I (AUC24h = -0.65 + 1.00 * C1 + 1.94 * C2
+ 15.45 * C9) had the best performances [adj-R2 = 0.93, median prediction error
(MPE) = -0.20, root median squared prediction error (RMSE) = 4.65 for Model H;
adj-R2 = 0.96, MPE = -0.05 RMSE = 3.56 for Model I]. The very high R2 values
(>=0.94) of these regression equations in the validation cohort confirmed their
high reliability. These LSS models could be applied in the context of therapeutic
drug monitoring programmes aiming to personalize isoniazid dosing regimens for
adult patients with tuberculosis.
PMID- 28495480
TI - [Fabien Arcelin (1876-1942), or how to become a radiation oncologist when born an
archeologist].
AB - Fabien Arcelin, physician working in Lyon, pioneer of radiology and radiotherapy,
was both mentored by Destot (one of the fathers of the French radiology for his
thesis of medicine) and by his own father Adrien Arcelin (one of the two
codiscoverers of the prehistorical site of the Roche-de-Solutre in Burgundy) for
archeological works. Hence, radiologist in Lyon during the week and archeologist
during the weekend, Fabien Arcelin made significant advances in both radiation
research and archeology. He was notably the discoverer of the first tombs of
Aurignacian men. In radiology, he examined about 2000 radiographic heart views
with the Destot's orthodiagraph to assess the cardiothoracic ratio and wrote a
reference book about the use of X-rays to detect kidney stones. He made the first
survey about the secondary effects of radiotherapy, important database for
pointing out individual radiosensitivity. In parallel to the radiotherapy trials
of Regaud at Curie institute (Paris), he performed the first series of anticancer
treatments in Lyon.
PMID- 28495478
TI - Determinants of Sugar-Sweetened Beverage Consumption among Low-Income Children:
Are There Differences by Race/Ethnicity, Age, and Sex?
AB - BACKGROUND: Understanding determinants of high consumption of sugar-sweetened
beverages (SSBs), a highly prevalent obesogenic behavior, will help build
effective customized public health interventions. OBJECTIVE: Our aim was to
identify child and parent lifestyle and household demographic factors predictive
of high SSB consumption frequency in children from low-income, ethnically diverse
communities that may help inform public health interventions. DESIGN: We used a
cross-sectional telephone household survey. PARTICIPANTS/SETTING: Participants
were 717 boys and 686 girls aged 3 to 18 years old from the New Jersey Childhood
Obesity Study living in five low-income cities (Camden, New Brunswick, Newark,
Trenton, and Vineland). The adult most knowledgeable about household food
shopping completed a questionnaire over the telephone inquiring about their and
their child's dietary and physical activity habits, and household-, parent-, and
child-level demographics. MAIN OUTCOME MEASURES: Child's SSB consumption
frequency was measured. STATISTICAL ANALYSIS PERFORMED: Multivariate ordered
logit models were designed to investigate a variety of variables hypothesized to
affect the frequency of SSB consumption. Exploratory stratified analyses by race,
sex, and age were also conducted. RESULTS: Eight percent of our study
participants never consumed SSBs, 45% consumed SSBs at least once per day, and
23% consumed twice or more per day. SSB consumption was higher among children 12
to 18 years vs 3 to 5 years (P<0.0001), of non-Hispanic black vs non-Hispanic
white race/ethnicity (P=0.010), who were moderate fast food consumers vs never
consumers (P=0.003), and those whose parents were high vs low SSB consumers
(P<0.0001). Living in a non-English-speaking household (P=0.030), having a parent
with a college or higher education vs less than high school (P=0.003), and having
breakfast 6 to 7 days/wk vs never to 2 days/wk or less were associated with lower
SSB consumption (P=0.001). CONCLUSIONS: We identified a number of household-,
parent-, and child-level predictors of SSB consumption, which varied by race,
sex, and age, useful for building customized interventions targeting certain
behaviors in ethnically diverse, low-income children.
PMID- 28495481
TI - Prediction of local control in early glottic carcinoma using the maximum
standardised uptake value.
AB - PURPOSE: This retrospective study aimed to determine whether the maximum
standardised uptake value (SUVmax) can predict local tumour control in early
glottic cancer (Tis, T1, and T2). PATIENTS AND METHODS: Fifty-nine patients
treated with definitive radiotherapy for early glottic cancer between 2003 and
2011 were enrolled. We evaluated the SUVmax in the region of interest around the
original tumour site. Local tumour control and survival were estimated using
Kaplan-Meier curves. Receiver operating characteristic curves were used to assess
the optimal SUVmax cut-off for predicting local control. RESULTS: As determined
by laryngoscopy, all patients achieved a complete response. Eleven patients
experienced local recurrence, while no distant metastasis occurred. One patient
died due to local recurrence, while five lost their larynxes. The median follow
up was 61.5 (range: 6.2-123.4) months. The five-year local progression-free
survival was 84.7%, and larynx preservation was possible in 89.6% of cases. The
median SUVmax was 2.2. The optimal SUVmax for predicting local tumour control was
identified as 3.4. Patients with glottic cancers with an SUVmax>3.4 showed a
significantly lower local progression-free survival rate than those with tumours
with an SUVmax<3.4 (five-year local progression-free survival rate: 53.4% vs.
95.4%, P<0.01). Multivariate analysis confirmed that a high SUVmax was an
independent predictive factor for local progression-free survival (P=0.006).
CONCLUSION: The use of (18F)-fluorodeoxyglucose-positron emission tomography for
evaluation of the SUVmax is useful to predict local progression-free survival in
patients with early glottic cancer treated by radiation. Early glottic cancer
with a high SUVmax may require aggressive local treatment and careful
surveillance.
PMID- 28495483
TI - Breast cancer: Is radiotherapy of internal mammary nodes the "state of the art"
or "reheating the cold dish"? About a discussion, review of the literature and
own opinion.
PMID- 28495482
TI - [Recurrence of a glassy cell carcinoma of the vagina: An exceptional situation].
AB - Glassy cell carcinoma is a rare neoplasm that occurs most frequently in the
uterine cervix. We describe the second reported case of glassy cell carcinoma
arising in the vagina. We present a case of a 24-year-old woman with a history of
post-coital bleeding associated with menometrorrhagia. Different explorations
have concluded in a glassy cell carcinoma arising in the vagina, with clinical
staging III according to the International Federation of Obstetrics and
Gynecology. The patient received three cycles of neoadjuvant chemotherapy with a
good response. Then she had a para-aortic lymphadenectomy and ovarian
transposition. Following the surgery, she had radiotherapy. The gynecological
examination showed no budding lesion and the biopsy was negative. Six months
later, the patient complained of a pelvic pain. The examination revealed a
locoregional recurrence. Surgical revision was not possible and the patient was a
candidate for a palliative chemotherapy. Although, glassy cell carcinoma runs an
aggressive clinical course, an early diagnosis may help in a more effective
management and offer a better prognosis.
PMID- 28495484
TI - Insights on Heme Synthesis in the Malaria Parasite.
AB - The malaria parasite has a functional heme-biosynthetic pathway, although it can
access host hemoglobin-heme. The heme pathway is dispensable for blood stages,
but essential in the mosquito stages which do not acquire hemoglobin-heme. We
propose that the blood stage parasites maintain a dynamic heme pool through
multiple back-up mechanisms.
PMID- 28495485
TI - Mosquito Biting Modulates Skin Response to Virus Infection.
AB - Mosquito-borne infections are increasing in number and are spreading to new
regions at an unprecedented rate. In particular, mosquito-transmitted viruses,
such as those that cause Zika, dengue, West Nile encephalitis, and chikungunya,
have become endemic or have caused dramatic epidemics in many parts of the world.
Aedes and Culex mosquitoes are the main culprits, spreading infection when they
bite. Importantly, mosquitoes do not act as simple conduits that passively
transfer virus from one individual to another. Instead, host responses to
mosquito-derived factors have an important influence on infection and disease,
aiding replication and dissemination within the host. Here, we discuss the latest
research developments regarding this fascinating interplay between mosquito,
virus, and the mammalian host.
PMID- 28495486
TI - March 2017 (vol. 216, no. 3, page 250).
PMID- 28495487
TI - Effect of Psychiatric Illness on Acute Care Utilization at End of Life From
Serious Medical Illness.
AB - CONTEXT: Little is known about psychiatric illness and utilization of end-of-life
care. OBJECTIVES: We hypothesized that preexisting psychiatric illness would
increase hospital utilization at end of life among patients with chronic medical
illness due to increased severity of illness and care fragmentation. METHODS: We
reviewed electronic health records to identify decedents with one or more of
eight chronic medical conditions based on International Classification of
Diseases-9 codes. We used International Classification of Diseases-9 codes and
prescription information to identify preexisting psychiatric illness. Regression
models compared hospital utilization among patients with and without psychiatric
illness. Path analyses examined the effect of severity of illness and care
fragmentation. RESULTS: Eleven percent of 16,214 patients with medical illness
had preexisting psychiatric illness, which was associated with increased risk of
death in nursing homes (P = 0.002) and decreased risk of death in hospitals (P <
0.001). In the last 30 days of life, psychiatric illness was associated with
reduced inpatient and intensive care unit utilization but increased emergency
department utilization. Path analyses confirmed an association between
psychiatric illness and increased hospital utilization mediated by severity of
illness and care fragmentation, but a stronger direct effect of psychiatric
illness decreasing hospitalizations. CONCLUSION: Our findings differ from the
increased hospital utilization for patients with psychiatric illness in
circumstances other than end-of-life care. Path analyses confirmed hypothesized
associations between psychiatric illness and increased utilization mediated by
severity of illness and care fragmentation but identified more powerful direct
effects decreasing hospital use. Further investigation should examine whether
this effect represents a disparity in access to preferred care.
PMID- 28495488
TI - Vascular Age, RR, ALLY, RALLY and Vascular Speed, Based on SCORE: Relations
Between New Concepts of Cardiovascular Prevention.
PMID- 28495489
TI - Optical Coherence Tomography Findings in Patients With Stent Thrombosis.
AB - INTRODUCTION AND OBJECTIVES: Stent thrombosis (ST) is a rare but potentially
serious complication. Optical coherence tomography (OCT) provides high-resolution
images and additional information to angiography in the study of this event.
METHODS: Prospective study of patients with ST undergoing reintervention with OCT
imaging. RESULTS: The study included a total of 40 consecutive patients with ST.
Mean age was 69 +/- 13 years and 83% were male. Early ST (<= 30 days) was
observed in 16 patients and late ST (> 30 days) in 24 patients. Stent thrombosis
occurred in 17 bare-metal stents and 23 drug-eluting stents. In 34 patients
(85%), adequate OCT images were obtained at the time of the ST. The predominant
mechanism in early ST was stent malapposition (39%). In late ST, high frequencies
of uncovered (46%) and malapposed struts (17%) were observed, especially in
patients with drug-eluting stents. Furthermore, the presence of
neoatherosclerosis was very high (67%) in patients with late ST. After
intervention, improvements were observed in malapposition length and the amount
of residual thrombus. CONCLUSIONS: OCT allows identification of the underlying
mechanisms potentially involved in ST. This imaging modality is helpful in
guiding reintervention in these patients, which improves the area and length of
malapposition, as well as the maximal residual thrombus area.
PMID- 28495490
TI - Further evidence for the association between LRP8 and schizophrenia.
AB - Previous studies (including genome-wide association study (GWAS) and candidate
gene studies) have revealed the important roles of genetic risk factors in
schizophrenia, and RELN has been identified as a risk gene for this illness. We
recently found that the low-density lipoprotein receptor-related protein 8
(LRP8), a receptor of Reelin (the protein encoded by RELN), was significantly
associated with schizophrenia and bipolar disorder in European populations. To
further enhance our understanding of its role in the risk of psychiatric
illnesses, we conducted meta-analyses of a higher density of single nucleotide
polymorphisms (SNPs, N=173) in LRP8 to understand their associations with
schizophrenia in much larger samples (39,400 cases and 50,357 controls) from
populations of European, Chinese and African American ancestries. The significant
risk SNPs then underwent further analyses to understand their correlations with
bipolar disorder and anxiety disorders, as well as LRP8 expression. We observed
that rs5177 in the 3' untranslated region (3'UTR) of LRP8 was associated with
schizophrenia and other psychiatric disorders, and rs5177 was also associated
with LRP8 mRNA expression. These data further support LRP8 as a schizophrenia
susceptibility gene, and suggest that this variant is likely a risk locus in
general populations.
PMID- 28495491
TI - A computational algorithm for personalized medicine in schizophrenia.
AB - Despite advances in sequencing candidate genes and whole genomes, no method has
accurately predicted who will or will not benefit from a specific antipsychotic
medication among patients with schizophrenia. We propose a computational
algorithm that utilizes a person-centered approach that directly identifies
individual patients who will respond to a specific antipsychotic medication. The
algorithm was applied to the data obtained from the Clinical Antipsychotic Trials
of Intervention Effectiveness (CATIE) study. The predictors were either (1) 13
single-nucleotide polymorphisms (SNPs) and 53 baseline variables or (2) 25 SNPs
and the same 53 baseline variables, depending on the existing findings and data
availability. The outcome variables were either (1) improvement in the Positive
and Negative Syndrome Scale (PANSS) (Yes/No) or (2) completion of phase 1/1A
(Yes/No). Each of those four predictor-outcome combinations was tried for each of
the five antipsychotic medications (Perphenazine, Olanzapine, Quetiapine,
Risperidone, and Ziprasidone), leading to 20 prediction experiments. For 18 out
of 20 experiments, all three performance measures were greater than 0.50
(sensitivity 0.51-0.79, specificity 0.52-0.79, accuracy 0.52-0.74). Notably, the
model provided a promising prediction for Ziprasidone for the case involving
completion of phase 1/1A (Yes/No) predicted by 13 SNPs and 53 baseline variables
(sensitivity 0.75, specificity 0.74, accuracy 0.74). The proposed algorithm
simultaneously used both genetic information and clinical profiles to predict
individual patients' response to antipsychotic medications. As the method is not
disease-specific but a general algorithm, it can be easily adopted in many other
clinical practices for personalized medicine.
PMID- 28495492
TI - The complex relationship between self-reported 'personal recovery' and clinical
recovery in schizophrenia.
AB - Self-reported 'personal recovery' and clinical recovery in schizophrenia (SRPR
and CR, respectively) reflect different perspectives in schizophrenia outcome,
not necessarily concordant with each other and usually representing the
consumer's or the therapist's point of view. By means of a cluster analysis on
SRPR-related variables, we identified three clusters. The first and third cluster
included subjects with the best and the poorest clinical outcome respectively.
The second cluster was characterized by better insight, higher levels of
depression and stigma, lowest self-esteem and personal strength, and highest
emotional coping. The first cluster showed positive features of recovery, while
the third cluster showed negative features. The second cluster, with the most
positive insight, showed a more complex pattern, a somewhat 'paradoxical' mixture
of positive and negative personal and clinical features of recovery. The present
results suggest the need for a characterization of persons with schizophrenia
along SRPR and CR dimensions to design individualized and integrated treatment
programs aimed to improve insight and coping strategies, reduce stigma, and shape
recovery styles.
PMID- 28495494
TI - Unlimited niche packing in a Lotka-Volterra competition game.
AB - A central question in the study of ecology and evolution is: "Why are there so
many species?" It has been shown that certain forms of the Lotka-Volterra (L-V)
competition equations lead to an unlimited number of species. Furthermore, these
authors note how any change in the nature of competition (the competition kernel)
leads to a finite or small number of coexisting species. Here we build upon these
works by further investigating the L-V model of unlimited niche packing as a
reference model and evolutionary game for understanding the environmental factors
restricting biodiversity. We also examine the combined eco-evolutionary dynamics
leading up to the species diversity and traits of the ESS community in both
unlimited and finite niche-packing versions of the model. As an L-V game with
symmetric competition, we let the strategies of individuals determine the
strength of the competitive interaction (like competes most with like) and also
the carrying capacity of the population. We use a mixture of analytic proofs (for
one and two species systems) and numerical simulations. For the model of
unlimited niche packing, we show that a finite number of species will evolve to
specific convergent stable minima of the adaptive landscape (also known as
species archetypes). Starting with a single species, faunal buildup can proceed
either through species doubling as each diversity-specific set of minima are
reached, or through the addition of species one-by-one by randomly assigning a
speciation event to one of the species. Either way it is possible for an
unlimited number or species to evolve and coexist. We examine two simple and
biologically likely ways for breaking the unlimited niche-packing: (1) some
minimum level of competition among species, and (2) constrain the fundamental
niche of the trait space to a finite interval. When examined under both
ecological and evolutionary dynamics, both modifications result in convergent
stable ESSs with a finite number of species. When the number of species is held
below the number of species in an ESS coalition, we see a diverse array of
convergent stable niche archetypes that consist of some species at maxima and
some at minima of the adaptive landscape. Our results support those of others and
suggest that instead of focusing on why there are so many species we might just
as usefully ask, why are there so few species?
PMID- 28495493
TI - The value of novelty in schizophrenia.
AB - Influential models of schizophrenia suggest that patients experience incoming
stimuli as excessively novel and motivating, with important consequences for
hallucinatory experience and delusional belief. However, whether schizophrenia
patients exhibit excessive novelty value and whether this interferes with
adaptive behaviour has not yet been formally tested. Here, we employed a three
armed bandit task to investigate this hypothesis. Schizophrenia patients and
healthy controls were first familiarised with a group of images and then asked to
repeatedly choose between familiar and unfamiliar images associated with
different monetary reward probabilities. By fitting a reinforcement-learning
model we were able to estimate the values attributed to familiar and unfamiliar
images when first presented in the context of the decision-making task. In line
with our hypothesis, we found increased preference for newly introduced images
(irrespective of whether these were familiar or unfamiliar) in patients compared
to healthy controls and this to correlate with severity of hallucinatory
experience. In addition, we found a correlation between value assigned to novel
images and task performance, suggesting that excessive novelty value may
interfere with optimal learning in patients, putatively through the disruption of
the mechanisms regulating exploration versus exploitation. Our results suggest
excessive novelty value in patients, whereby even previously seen stimuli acquire
higher value as the result of their exposure in a novel context - a form of
'hyper novelty' which may explain why patients are often attracted by familiar
stimuli experienced as new.
PMID- 28495496
TI - Aggressive digital papillary adenocarcinoma: A clinicopathological study of 19
cases.
AB - BACKGROUND: Aggressive digital papillary adenocarcinomas (ADPA) are malignant
tumors of sweat glands having recurrence/metastatic potential. OBJECTIVE: We
sought to describe the clinical/histopathological characteristics of a series of
ADPA. METHODS: This is a retrospective case series of 19 ADPA. RESULTS: The
tumors occurred in 17 men and 2 women (mean age: 47 years). They involved digits
(15), big toe (3), and palm (1), and measured from 3 to 30 mm. They were mostly
solid and cystic, with papillary projections and tubular structures. Atypia was
mostly mild to moderate. Tumors tested positive for p63, keratin 7, keratin 77
(eccrine duct-specific), PHLDA1, and epithelial membrane antigen in most cases,
and for carcinoembryonic antigen, smooth muscle actin, S100 protein, estrogen,
progesterone, and androgen receptors in 50%. Mean Ki67 proliferation index was
15%. Local recurrence was observed in 4 cases. One patient had axillary lymph
node metastasis. Histopathologic parameters were not predictive of evolution.
Conservative surgical treatment, performed in 7 of 19 cases, did not result in
more recurrences than amputation. LIMITATIONS: The study was retrospective and
the number of cases is small. CONCLUSION: ADPA are histologically variable, but
papillary projections are always present. Keratin 77 expression suggests an
eccrine origin. P63 is helpful to exclude metastasis. Conservative surgery may be
sufficient in some cases.
PMID- 28495498
TI - Venous thromboembolism in patients with pemphigus: A cohort study.
AB - BACKGROUND: Venous thromboembolism (VTE) has been reported to be a significant
cause of death in patients with pemphigus. OBJECTIVE: We sought to assess the
incidence and characteristics of VTE in patients with pemphigus. METHODS: A
retrospective study following a cohort of 172 patients with newly diagnosed
pemphigus for the development of VTE was conducted. RESULTS: Over a mean follow
up time of 4 years, 10 patients (6%) had development of VTE at a median of 4
months from pemphigus diagnosis. The highest risk was found in the first year, at
5 VTE events per 100 patient-years or a 5% VTE risk for that first year. Five
patients had deep vein thromboses, 4 had pulmonary embolisms, and 1 had both. Age
and gender were not related to the VTE risk. Most patients had VTE risk factors,
either hereditary or acquired as the result of pemphigus treatments and their
complications, including hospitalization, immobilization, and infections.
LIMITATIONS: The use of existing health records limited the assessment of
asymptomatic VTE and VTE risk factors; a matched control population was not
studied. CONCLUSIONS: VTEs are not rare in patients with pemphigus, more so in
the first year after diagnosis. VTE risk must be assessed in all patients,
especially when hospitalized, and thrombo-prophylaxis should be initiated in
qualifying cases.
PMID- 28495495
TI - Translating in vitro ligand bias into in vivo efficacy.
AB - It is increasingly apparent that ligand structure influences both the efficiency
with which G protein-coupled receptors (GPCRs) engage their downstream effectors
and the manner in which they are activated. Thus, 'biased' agonists, synthetic
ligands whose intrinsic efficacy differs from the native ligand, afford a
strategy for manipulating GPCR signaling in ways that promote beneficial signals
while blocking potentially deleterious ones. Still, there are significant
challenges in relating in vitro ligand efficacy, which is typically measured in
heterologous expression systems, to the biological response in vivo, where the
ligand is acting on natively expressed receptors and in the presence of the
endogenous ligand. This is particularly true of arrestin pathway-selective
'biased' agonists. The type 1 parathyroid hormone receptor (PTH1R) is a case in
point. Parathyroid hormone (PTH) is the principal physiological regulator of
calcium homeostasis, and PTH1R expressed on cells of the osteoblast lineage are
an established therapeutic target in osteoporosis. In vitro, PTH1R signaling is
highly sensitive to ligand structure, and PTH analogs that affect the
selectivity/kinetics of G protein coupling or that engage arrestin-dependent
signaling mechanisms without activating heterotrimeric G proteins have been
identified. In vivo, intermittent administration of conventional PTH analogs
accelerates the rate of osteoblastic bone formation, largely through known cAMP
dependent mechanisms. Paradoxically, both intermittent and continuous
administration of an arrestin pathway-selective PTH analog, which in vivo would
be expected to antagonize endogenous PTH1R-cAMP signaling, also increases bone
mass. Transcriptomic analysis of tissue from treated animals suggests that
conventional and arrestin pathway-selective PTH1R ligands act in largely
different ways, with the latter principally affecting pathways involved in the
regulation of cell cycle, survival, and migration/cytoskeletal dynamics. Such
multi-dimensional in vitro and in vivo analyses of ligand bias may provide
insights into the physiological roles of non-canonical arrestin-mediated
signaling pathways in vivo, and provide a conceptual framework for translating
arrestin pathway-selective ligands into viable therapeutics.
PMID- 28495497
TI - Risk for hepatitis B and C virus reactivation in patients with psoriasis on
biologic therapies: A retrospective cohort study and systematic review of the
literature.
AB - BACKGROUND: Patients with psoriasis on biologic therapies and a history of viral
hepatitis carry a risk for reactivation. OBJECTIVE: We evaluated safety of
biologic therapies in psoriasis patients seropositive for hepatitis B or C
viruses (HBV, HCV). METHODS: A retrospective cohort study design was used.
Clinical and laboratory data for 30 patients undergoing biologic therapy who were
seropositive for HBV or HCV were evaluated. Next, a systematic review was
performed. Primary outcomes were hepatitis and viral reactivation during therapy.
Treatment duration and antiviral prophylaxis were also recorded. RESULTS:
Serology indicated HCV infection in 4 patients, past HBV infection in 17
patients, isolated core antibody in 8 patients, and chronic HBV infection in 1
patient. During follow-up (mean 4.85 +/- 3.1 years), no patients experienced
hepatitis or viral reactivation. The systematic review of the literature included
49 studies comprising 312 patients followed for a mean of 30.9 months. Viral
reactivation occurred in 2/175 patients who were seropositive for core antibody
and 3/97 with HCV infection (yearly rates, 0.32% and 2.42%, respectively)
compared with 8/40 patients with chronic HBV infection (yearly rate, 13.92%).
Three of these 8 patients with reactivated HBV infection received antiviral
prophylaxis. LIMITATIONS: We pooled heterogeneous studies evaluating different
biologic therapies. CONCLUSION: Biologic therapies pose minimal risk for viral
reactivation in low-risk patients without hepatitis seropositive for HCV or HBV
core antibody but are a considerable risk in patients with chronic HBV infection,
highlighting the necessity of antiviral prophylaxis.
PMID- 28495499
TI - Definitive radiotherapy for Merkel cell carcinoma confers clinically meaningful
in-field locoregional control: A review and analysis of the literature.
AB - BACKGROUND: Merkel cell carcinoma (MCC) is an uncommon radiosensitive,
neuroendocrine malignancy. Treatment often involves surgery; however, older,
sicker patients may not be candidates for an operation. Institutions have
published data favoring the role of definitive radiotherapy for macroscopic
locoregional disease. OBJECTIVE: Our objective was to report the outcome of
patients treated with definitive radiotherapy. METHODS: We performed a systematic
review of Medline, PubMed, and Embase databases for reported cases or series of
definitive radiotherapy for macroscopic locoregional MCC. RESULTS: The mean
radiation dose did not significantly differ between primary and regional sites
(48.7 +/- 13.2 vs 49.4 +/- 10.1 Gy, P = .74). The rate of recurrence was
calculated on the basis of the site of disease (11.7%) and per patient (14.3%).
Recurrence was significantly more likely to occur at regional than at primary
irradiated sites (16.3% vs 7.6%, P = .02). There was no association between
radiotherapy dose and incidence of recurrence or nonrecurrence; primary (42.7 +/-
23 vs 49.3 +/- 11.8 Gy, P = .197) and regional (48.6 +/- 10 vs 49.5 +/- 10.3 Gy,
P = .77). LIMITATIONS: A limitation of this report is that most publications were
retrospective; heterogeneity was present in the size of MCC and in radiotherapy
details. CONCLUSIONS: Definitive radiotherapy for locoregional macroscopic MCC
was found to confer clinically meaningful local and regional in-field control.
PMID- 28495500
TI - Microemulsion utility in pharmaceuticals: Implications for multi-drug delivery.
AB - Emulsion technology has been utilized extensively in the pharmaceutical industry.
This article presents a comprehensive review of the literature on an important
subcategory of emulsions, microemulsions. Microemulsions are optically
transparent, thermodynamically stable colloidal systems, 10-100nm diameter, that
form spontaneously upon mixing of oil, water and emulsifier. This review is the
first to address advantages and disadvantages, as well as considerations and
challenges in multi-drug delivery. For the period 1 January 2011-30 April 2016,
431 publications related to microemulsion drug delivery were identified and
screened according to microemulsion, drug classification, and surfactant types.
Results indicate the use of microemulsions predominantly in lipophilic drug
delivery (79.4%) via oil-in-water microemulsions and non-ionic surfactants (90%)
for oral or topical administration. Cancer is the disease state most targeted
followed by inflammatory diseases, microbial infections and cardiovascular
disease. Key generalizations from this analysis include: 1) microemulsion
formulation is largely based on trial-and-error despite over 1200 publications
related to microemulsion drug delivery since their discovery in 1943; 2)
characterization using methods including interfacial tension, droplet size,
electrical conductivity, turbidity and viscosity may provide additional
information for greater predictability; 3) microemulsion drug delivery
publications arise primarily from China (27%) and India (21%) suggesting
additional research opportunities elsewhere.
PMID- 28495501
TI - Semen modulated secretory activity of oviductal epithelial cells is linked to
cellular proteostasis network remodeling: Proteomic insights into the early phase
of interaction in the oviduct in vivo.
AB - : The oviductal epithelium is crucial for the integrity of the female organ.
Previously we got evidence that the surface proteome of oviductal epithelial
cells (Oecs) is promptly altered in response to insemination and thus suggested
that this early phase plays a notable regulatory role in maintaining cellular
function. This study further aimed to assess the effect of semen on the cellular
and molecular mechanisms in rabbit Oecs. A quantitative gel-based proteomic
approach was applied to analyze changes at three time points (0h, 1h, 2h) after
intrauterine insemination (IUI) compared to time matched controls. Within two
hours the abundance of 22 protein species was evidently altered in the
intracellular fraction. Functional analysis revealed that the proteins were
primarily involved in proteostasis as well as metabolic processes. The analysis
of phosphoproteins specified a role of mitogen-activated protein kinase (MAPK)
signaling molecules. Concurrently, semen increased oviduct-specific glycoprotein
(OVGP1) secretion. A correlation between OVGP1 abundance and microtubule
associated proteins 1A/1B-light chain 3 lipidation was observed. The localization
and changes in abundance of selected proteins were corroborated by antibody-based
methods. These results clearly show that the early phase of interaction acts as a
trigger for cellular adaptation to meet an altered demand in the female organ.
SIGNIFICANCE: The oviductal epithelium and its secreted proteins exert a pivotal
role in reproductive processes, including the final maturation of male gametes.
Thereby, the regulation and subsequently the functionality of the oviductal
epithelial cell layer are important factors for the establishment of the
appropriate milieu in the female reproductive tract. Notably, male gametes
themselves have been shown to be an extrinsic modulatory factor of the oviductal
epithelium. Accordingly a comprehensive knowledge about the underlying cellular
and molecular mechanisms in the epithelial cells is of interest, also with regard
to in vitro purposes. So far, the role of the early phase of interaction in the
female organ has not been considered in detail. To get a further insight into the
underlying cellular and molecular mechanisms, herein we analyzed the effect of
semen on oviductal epithelial cells (Oecs) on the intracellular proteome level
within the first two hours after insemination. The present study revealed a
directed response of Oecs in vivo and disclosed intracellular pathways that are
affected by the interplay between semen and the female reproductive tract. The
prompt adaptation of the secretory activity and remodeling of the oviductal
epithelium was accompanied by the concerted alterations of protein species that
are primarily involved in the maintenance of cellular homeostasis. Besides
emphasizing the importance of the early interaction phase for subsequent
reproductive processes, the gained knowledge might further be implemented for in
vitro applications as well.
PMID- 28495502
TI - Multipronged quantitative proteomics reveals serum proteome alterations in breast
cancer intrinsic subtypes.
AB - : Being molecularly heterogeneous, breast cancer tends to be a complicated
oncological disease with high incidence rates throughout the world. The primary
aim of this study was to identify the set of serum proteins with discriminatory
capabilities towards the four major subtypes of breast cancer. We employed
multipronged quantitative proteomic approaches like 2D-DIGE, iTRAQ and SWATH-MS
and identified 307 differentially regulated proteins. Luminal A subtype consisted
of 24, Luminal B subtype 38, HER2 Enriched subtype 17 and Triple negative breast
cancer subtype 10 differentially regulated subtype specific proteins. These
specific proteins were further subjected to bioinformatic tools which revealed
the involvement in platelet degranulation, fibrinolysis, lipid metabolism, immune
response, complement activation, blood coagulation, glycolysis and cancer
signaling pathways in the subtypes of the breast cancer. The significant
discrimination efficiency of the models generated through multivariate
statistical analysis was decent to distinguish each of the four subtypes from
controls. Further, some of the statistically significant differentially regulated
proteins were verified and validated by immunoblotting and mass spectrometry
based selected reaction monitoring (SRM) approach. Our Multipronged proteomics
approaches revealed panel of serum proteins specifically altered for individual
subtypes of breast cancer. The mass spectrometry data are available via
ProteomeXchange with identifier PXD006441. BIOLOGICAL SIGNIFICANCE: Worldwide,
breast cancer continues to be one of the leading causes of cancer related deaths
in women and it encompasses four major molecular subtypes. As breast cancer
treatment majorly depends on identification of specific subtype, it is important
to diagnosis the disease at subtype level. Our results using multipronged
quantitative proteomics identified 307 differentially regulated proteins in which
24 were specific for Luminal A, 38 for Luminal B, 17 for HER2 enriched and 10
proteins were specific for TN subtype. Bioinformatic analysis of these proteins
revealed certain biological processes and pathways altered at subtype level and
validation experiments of some of these proteins using immunoblotting and SRM
assays are consistent with discovery data. This is the first comprehensive
proteomic study on serum proteome alterations at subtype level which will not
only help to distinguish subtype of breast cancer but also contribute to a better
understanding of the molecular characteristic of breast cancer at individual
subtype level.
PMID- 28495503
TI - Sex-differences in the prevalence of Helicobacter pylori infection in pediatric
and adult populations: Systematic review and meta-analysis of 244 studies.
AB - BACKGROUND: The main outcome of Helicobacter pylori infection, i.e. gastric
cancer, is more frequent in men, but there is no comprehensive synthesis of the
evidence on a potential role of sex in the acquisition and/or persistence of
infection. AIMS: To quantify the association between sex and H. pylori infection
in pediatric and adult populations, through systematic review and meta-analysis.
METHODS: PubMed(r) was searched, from inception to September 2015, to identify
population-based studies reporting the prevalence and/or incidence of H. pylori
infection in both sexes. Odds ratios (OR) or data to compute them were extracted;
adjusted estimates were preferred, whenever available. The DerSimonian and Laird
method was used to compute summary estimates and respective 95% confidence
intervals (95%CI), separately for children and adults. RESULTS: Among a total of
244 studies, mostly cross-sectional, male sex was associated with a greater
prevalence of H. pylori infection, both in children (102 studies, OR=1.06, 95%CI:
1.01, 1.12, I2=43.7%) and adults (169 studies, OR=1.12, 95%CI: 1.09, 1.15,
I2=68.5%). An underrepresentation of studies showing a negative association
between male sex and infection was observed (Egger's test: p=0.006). CONCLUSIONS:
Although further research is needed to understand the mechanisms by which sex may
influence the acquisition and/or persistence of infection, our results support a
small contribution of sex differences in the prevalence of infection to the male
predominance of H. pylori-related outcomes, including gastric cancer.
PMID- 28495504
TI - Renal Arterial Mycotic Aneurysm After Kidney Transplantation.
AB - Mycotic aneurysm is a rare condition mostly attributable to Candida or
Aspergillus species. About 20 cases of Candida-related arteritis have been
reported in kidney transplant patients. Herein, we report the case of a 40-year
old man who received a kidney from a deceased donor in whom an accidental
digestive wound was made during organ retrieval. He presented with sudden anuria
47 days after renal transplantation, revealing a large mycotic aneurysm of the
kidney graft renal artery. Organs derived from donors in whom a digestive breach
is noticed should be used with caution.
PMID- 28495505
TI - Penile Fracture Following a Fall in a 7-Year-Old Male.
AB - We report a rare case of isolated penile fracture in a prepubescent male caused
by an accidental fall. The patient presented with swelling and ecchymosis on the
base of the penis and along the penile shaft. A flexible cystoscopy was
performed, which did not reveal any concomitant urethral injury. The penis was
degloved and the corporal tear was closed with absorbable suture. Due to the
location of the injury, ventral mobilization of the urethra was required. The
pathophysiology of penile fracture as well as the diagnosis and management of
this rare injury are discussed in this report.
PMID- 28495506
TI - Use of Bipedicled Dorsal Penile Flap With Z Release Incision: A New Option in
Redo Hypospadias Surgery.
AB - OBJECTIVE: To solve the challenge in redo hypospadias surgery, we tried to use a
bipedicled dorsal penile flap with a Z release incision in failed hypospadias
cases and reported the outcome. MATERIALS AND METHODS: Thirty male children with
3 or 4 previous unsuccessful hypospadias surgeries were included in our study.
Our technique was done after at least 6 months from the last surgery. A flap of
the dorsal penile skin was preserved and the skin lateral to the flap was
dissected on each side. A small opening was done in the dartos proximal to flap.
The glans was withdrawn through this opening with a ventral transposition of the
flap. Z-plasty was used to compensate for the deficient dorsal skin; the Z-plasty
had 3 limbs and all were made of equal length. RESULTS: The mean age of the
patients was 5.4 +/- 1.8 years and the mean follow-up was 2.1 +/- 0.7 years. The
technique was successful in 80%. Reoperation was required in 3 cases; all cases
were managed using a 2-stage buccal mucosal graft. A small fistula at the coronal
level developed in 2 cases but closed spontaneously within 1 month. All patients
were voiding well and had a vertically oriented meatus at the tip of the glans
and satisfactory cosmetic results. CONCLUSION: Repair of failed hypospadias using
a bipedicled dorsal penile skin flap with Z release incision is a safe and simple
procedure offering high success rates.
PMID- 28495507
TI - Up and Away: Five Decades of Urologic Investigation in Microgravity.
AB - A renewed global interest in manned space exploration has emerged, propelled by
the challenge of reaching a new frontier: travel to the Red Planet, Mars. As the
physiological changes induced by microgravity bear direct relevance to the safety
and viability of these goals, we provide a historical narrative of the urologic
investigations in space. We review the significant contributions to the
understanding of the urologic consequences associated with exposure to
microgravity, considerations for prolonged missions, and forward-looking efforts
to manage emergent conditions remotely. Historical insights gleaned are poised to
inform interplanetary travel, where urologic pathology will remain an important
practical consideration.
PMID- 28495508
TI - The effect of ALA-PDT under normoxia and cobalt chloride (CoCl2)-induced hypoxia
on adhesion molecules (ICAM-1, VCAM-1) secretion by colorectal cancer cells.
AB - BACKGROUND: The most fundamental problem in cancer biology research is to
understand the mechanisms of cancer cell resistance to oncological therapies.
Literature reports emphasize the important role of adhesion molecules:
intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 (ICAM-1
and VCAM-1) in cancer progression and resistance to treatment. Photodynamic
therapy (PDT) could become the component of a personalized approach to colorectal
cancer, therefore we examined the effects of ALA (delta-aminolevulinic) acid PDT
in normoxia and under cobalt chloride (CoCl2)-induced hypoxia on ICAM-1 and VCAM
1 secretion by colorectal cancer cells. METHODS: Human colorectal cancer cells of
different malignant potential SW480 and SW620 were used in the experiment. Cell
lines were treated ALA, in order to achieve conditions comparable to in vivo
hypoxia, CoCl2 was added, then cells were irradiated both in normoxia and in
hypoxia-like conditions. Cell viability was assessed using the LDH and MTT assays
and apoptosis. ICAM-1 and VCAM-1 concentrations were determined with the Bio -
Plex ProTM Assay and System. RESULTS: The experiment revealed that ALA PDT under
normoxia and CoCl2-induced hypoxia had no significant effect on ICAM-1 and VCAM-1
dependent adhesion of colorectal cancer cells. The secretion of ICAM-1 by SW480
ell line was more pronounced compared to ICAM-1 secretion by SW620 cells.
CONCLUSION: Determination of tumor marker levels and especially adhesion
molecules involved in metastatic spread is necessary. Our experiment reveals,
that ALA PDT in normoxia and CoCl2-induced hypoxia has no effect on adhesion
molecules secretion by colon cancer cells in vitro.
PMID- 28495509
TI - Cloning of three heat shock protein genes (HSP70, HSP90alpha and HSP90beta) and
their expressions in response to thermal stress in loach (Misgurnus
anguillicaudatus) fed with different levels of vitamin C.
AB - Heat shock protein 70 (HSP70) and 90 (HSP90) are the most broadly studied
proteins in HSP families. They play key roles in cells as molecular chaperones,
in response to stress conditions such as thermal stress. In this study, full
length cDNA sequences of HSP70, HSP90alpha and HSP90beta from loach Misgurnus
anguillicaudatus were cloned. The full-length cDNA of HSP70 in loach was 2332bp
encoding 644 amino acids, while HSP90alpha and HSP90beta were 2586bp and 2678bp
in length, encoding 729 and 727 amino acids, respectively. The deduced amino acid
sequences of HSP70 in loach shared the highest identity with those of Megalobrama
amblycephala and Cyprinus carpio. The deduced amino acid sequences of HSP90alpha
and HSP90beta in loach both shared the highest identity with those of M.
amblycephala. Their mRNA tissue expression results showed that the maximum
expressions of HSP70, HSP90alpha and HSP90beta were respectively present in the
intestine, brain and kidney of loach. Quantitative real-time PCR was employed to
analyze the temporal expressions of HSP70, HSP90alpha and HSP90beta in livers of
loaches fed with different levels of vitamin C under thermal stress. Expression
levels of the three HSP genes in loach fed the diet without vitamin C
supplemented at 0 h of thermal stress were significantly lower than those at 2 h,
6 h, 12 h and 24 h of thermal stress. It indicated that expressions of the three
HSP genes were sensitive to thermal stress in loach. The three HSP genes in
loaches fed with 1000 mg/kg vitamin C expressed significantly lower than other
vitamin C groups at many time points of thermal stress, suggesting 1000 mg/kg
dietary vitamin C might decrease the body damages caused by the thermal stress.
This study will be of value for further studies into thermal stress tolerance in
loach.
PMID- 28495510
TI - In vitro characterization of grass carp (Ctenopharyngodon idella) IL-26 in
regulating inflammatory factors.
AB - Interleukin 26 (IL-26) gene has been identified in human, amphibian and teleost
but not in rodents. It is well accepted that IL-26 was a crucial member of IL-10
family which acts as a pro-inflammatory cytokine in human. However, the role of
IL-26 in regulating inflammation in lower vertebrates including teleost has not
been defined yet. In the present study, grass carp IL-26 (gcIL-26) coding
sequence was isolated and identified. Its chromosomal synteny was also analyzed,
showing that gcIL-26 gene is flanked by IL-22 and IFN-gamma genes with the same
transcriptional orientation as seen in human, amphibian and zebrafish. Given that
zebrafish and grass carp IL-26 shared relatively low amino acid identities with
human IL-26, the functional roles of fish IL-26 are indispensable to be
elucidated. Accordingly, recombinant gcIL-26 (rgcIL-26) was prepared by using
Pichia pastoris expression system, and it was found to be partially glycosylated.
Using grass carp head kidney leucocytes as cell model, rgcIL-26 displayed the
bioactivity to stimulate the mRNA expression of some pro-inflammatory cytokines
including IL-8, IL-1beta and IL-6, while inhibit mRNA expression of an anti
inflammatory cytokine, IL-10. Moreover, rgcIL-26 also up-regulated inos
expression and NO production in grass carp monocytes/macrophages, strengthening
its pro-inflammatory properties in fish. Those results collectively demonstrated
the functional role of IL-26 in regulating inflammatory response in fish.
PMID- 28495511
TI - Biomolecular NMR: Past and future.
AB - The editors of this special volume suggested this topic, presumably because of
the perspective lent by our combined >90-year association with biomolecular NMR.
What follows is our personal experience with the evolution of the field, which we
hope will illustrate the trajectory of change over the years. As for the future,
one can confidently predict that it will involve unexpected advances. Our
narrative is colored by our experience in using the NMR Facility for Biomedical
Studies at Carnegie-Mellon University (Pittsburgh) and in developing similar
facilities at Purdue (1977-1984) and the University of Wisconsin-Madison (1984-).
We have enjoyed developing NMR technology and making it available to
collaborators and users of these facilities. Our group's association with the
Biological Magnetic Resonance data Bank (BMRB) and with the Worldwide Protein
Data Bank (wwPDB) has also been rewarding. Of course, many groups contributed to
the early growth and development of biomolecular NMR, and our brief personal
account certainly omits many important milestones.
PMID- 28495512
TI - Modulation of CASC2/miR-21/PTEN pathway sensitizes cervical cancer to cisplatin.
AB - Cisplatin (DDP) -based chemotherapy is a standard strategy for cervical cancer,
while chemoresistance remains a challenge. Recent evidence highlights the crucial
regulatory roles of long non-coding RNAs (lncRNA) in tumor biology. However, the
roles and regulatory mechanisms of the novel lncRNA, cancer susceptibility
candidate 2 (CASC2), in cervical cancer tumorigenesis and chemoresistance are
poorly understood. In this study, CASC2 expression was down-regulated in cervical
cancer tissues, and was related to a shorter survival time and poorer
clinicopathologic features. Exogenous CACS2 alone was sufficient to inhibit
cervical cancer cell proliferation and amplified DDP-induced repression of cell
proliferation. A lower expression of CACS2 was observed in the DDP-resistant
cervical cancer tissues, compared to DDP-sensitive cancer tissues; CACS2
overexpression could sensitize DDP-resistant cervical cancer cell (HeLa/DDP and
CaSki/DDP) to DDP. Further functional experiments indicate that CASC2 upregulated
PTEN expression by direct inhibiting miR-21 in the DDP-resistant cancer cells,
leading to the down-regulation of p-AKT protein. In DDP-resistant cervical cancer
tissues, miR-21 was up-regulated while PTEN was down-regulated. Taken together,
these observations suggest CASC2 up-regulates PTEN as a ceRNA of miR-21 and plays
an important role in cervical cancer sensitivity to DDP and may serve as a
potential target for cancer diagnosis and treatment.
PMID- 28495513
TI - High hydrostatic pressure affects antigenic pool in tumor cells: Implication for
dendritic cell-based cancer immunotherapy.
AB - High hydrostatic pressure (HHP) can be used to generate dendritic cell (DC)-based
active immunotherapy for prostate, lung and ovarian cancer. We showed here that
HHP treatment of selected human cancer cell lines leads to a degradation of tumor
antigens which depends on the magnitude of HHP applied and on the cancer cell
line origin. Whereas prostate or ovarian cell lines displayed little protein
antigen degradation with HHP treatment up to 300MPa after 2h, tumor antigens are
hardly detected in lung cancer cell line after treatment with HHP 250MPa at the
same time. On the other hand, quick reduction of tumor antigen-coding mRNA was
observed at HHP 200MPa immediately after treatment in all cell lines tested. To
optimize the DC-based active cellular therapy protocol for HHP-sensitive cell
lines the immunogenicity of HHP-treated lung cancer cells at 150, 200 and 250MPa
was compared. Lung cancer cells treated with HHP 150MPa display characteristics
of immunogenic cell death, however cells are not efficiently phagocytosed by DC.
Despite induction of the highest number of antigen-specific CD8+ T cells, 150 MPa
treated lung cancer cells survive in high numbers. This excludes their use in DC
vaccine manufacturing. HHP of 200MPa treatment of lung cancer cells ensures the
optimal ratio of efficient immunogenic killing and delivery of protein antigens
in DC. These results represent an important pre-clinical data for generation of
immunogenic killed lung cancer cells in ongoing NSCLC Phase I/II clinical trial
using DC-based active cellular immunotherapy (DCVAC/LuCa).
PMID- 28495514
TI - Neurobehavioral risks of SSRIs in pregnancy: Comparing human and animal data.
AB - During the last twenty years, in spite of extensive literature regarding the use
of SSRIs in pregnancy, confusion still exists as to possible long-term risks of
these drugs on the offspring. Possible negative effects relate to
neurodevelopmental outcome and association with Autism Spectrum Disorder (ASD).
Most neurodevelopmental follow up studies did not find significant cognitive
impairment except from some apparently transient, gross motor delay and slight
impairment of language abilities. The literature on the possible association of
SSRIs with ASD is inconsistent, and if an association exists it is apparently
throughout pregnancy. There is a higher risk for psychiatric problems which might
be related to the maternal psychiatric disease for which SSRIs were prescribed.
Most animal studies did not demonstrate teratogenicity, and the observed
neurodevelopmental problems are of models with depression induced during
pregnancy. Depression seems to be associated with up regulation of hypothalamic
pituitary adrenal (HPA) axis and prenatal SSRIs also seem to affect the HPA axis
in animals and man, but the possible long-term outcome has yet to be established.
SSRIs might apparently also induce epigenetic changes. There is, however, little
proof for significant damaging effects of SSRIs in pregnancy. When evaluating the
risk/benefit ratio of SSRI treatment in pregnancy, the risk associated with
treatment discontinuation e.g. higher frequency of relapse and postpartum
depression appears to outweigh the potential risks of treatment. Moreover,
maternal depression may negatively affect the child's development, emphasizing
the importance of prevention by appropriate treatment during pregnancy with the
least minimal effective dose.
PMID- 28495515
TI - Renal protective effects of thymoquinone against sodium nitrite-induced chronic
toxicity in rats: Impact on inflammation and apoptosis.
AB - AIMS: Sodium nitrite is a widely used color fixative and preservative. However,
it has been reported to exert deleterious toxic effects on various body organs.
Moreover, thymoquinone (TQ), the active constituent of Nigella sativa oil is
known to possess beneficial antioxidant and anti-inflammatory effects. The
present study was conducted to evaluate the potential protective effects of TQ
against sodium nitrite-induced renal toxicity. MAIN METHODS: Male Sprague-Dawley
rats were treated with sodium nitrite (80mg/kg, po, daily) in presence or absence
of TQ (25 and 50mg/kg, po, daily). Morphological changes in renal sections were
assessed by staining with Hematoxylin/Eosin and Periodic acid-Schiff. Renal
homogenate was used for measurement of oxidative stress markers (MDA and GSH),
inflammatory markers (CRP, TNF-alpha, IL-6, IL-1beta), anti-inflammatory
cytokines (IL-10 and IL-4) and apoptotic markers (caspase-3/caspase-8/caspase-9).
KEY FINDINGS: Treatment with sodium nitrite significantly increased markers of
renal dysfunction, oxidative stress, inflammation and apoptosis. These effects
were markedly attenuated by TQ in dose dependent manner. SIGNIFICANCE: TQ has a
potential protective effect against sodium nitrite-induced renal toxicity. This
can be attributed to its ability to dampen oxidative stress, restore the normal
balance between pro- and anti-inflammatory cytokines and protect renal tissue
form extrinsic and intrinsic apoptosis.
PMID- 28495516
TI - 7-O-geranylquercetin-induced autophagy contributes to apoptosis via ROS
generation in human non-small cell lung cancer cells.
AB - AIMS: To investigate the antitumor effects of 7-O-geranylquercetin (GQ), a novel
O-alkylated derivative of quercetin, against non-small cell lung cancer (NSCLC)
cell lines A549 and NCI-H1975 and the corresponding mechanisms. MAIN METHODS:
Cell viability was assessed using MTT assay. The expression of proteins involved
in apoptosis and autophagy was measured using western blotting. Besides,
apoptosis was determined with DAPI staining, Annexin V-PI staining and
transmission electron microscopy (TEM) assay, and autophagy was observed with TEM
assay. Cell cycle and reactive oxygen species (ROS) level were detected using
flow cytometry. KEY FINDINGS: GQ inhibited viability of A549 and NCI-H1975 cells
in a dose- and time-dependent manner without apparent cytotoxicity to normal
human lung fibroblast cells. GQ down-regulated the expression of apoptosis
related proteins pro-caspase 3 and Bcl-2, and up-regulated the expression of
cleaved-PARP and Bax in A549 and NCI-H1975 cells. Meanwhile, GQ-induced cell
apoptosis could be attenuated by caspase inhibitor Z-VAD-FMK. Besides, GQ induced
autophagosome formation in A549 and NCI-H1975 cells, promoted the expression of
autophagy-related proteins LC3-II and Beclin 1, and suppressed the expression of
p62. Autophagy inhibition with chloroquine or Beclin 1 siRNA could effectively
inhibit GQ-induced apoptosis. Furthermore, GQ treatment increased the generation
of ROS, and ROS inhibitor N-acetylcysteine could reverse GQ-induced autophagy and
apoptosis. Taken together, GQ could induce apoptosis and autophagy via ROS
generation in A549 and NCI-H1975 cells, and GQ-induced autophagy contributed to
apoptosis. SIGNIFICANCE: Our findings highlight that GQ is a promising anticancer
agent for the treatment of lung cancer.
PMID- 28495517
TI - Berberine confers neuroprotection in coping with focal cerebral ischemia by
targeting inflammatory cytokines.
AB - SCOPE: Existing research indicates that anti-inflammatory and antioxidant
properties of berberine play major roles in coping with oxidative stress in
neurodegenerative diseases, but it is not known if this isoquinoline alkaloid
affects inflammatory cytokines such as interleukin 10 in focal cerebral ischemia.
METHODS AND RESULTS: Male Wistar rats (10 weeks old) were treated with 40mg/kg
concentration of berberine 1h after focal cerebral ischemia and the anti
inflammatory properties of berberine were evaluated by immunohistochemical
analysis, water content measure and behavioral tests. Evaluation of infarct
volume was performed by TTC staining. Immunohistochemistry and behavioral
assessment indicated recovery in treatment group compared to only ischemia group.
The infarct volume decreased in treatment group compared to ischemia group.
Berberine administration significantly decreased brain edema and contributed to
the restoration of motor function. Moreover, berberine potently contributed to
neuroprotection in motor area through downregulation of pro-inflammatory
cytokines and upregulation of anti-inflammatory cytokines. CONCLUSIONS: These
findings confirm the validity of berberine as a potent anti-inflammatory agent in
treatment of ischemic stroke.
PMID- 28495518
TI - Prenatal exposure to low-dose diclofenac sodium does not affect total neuron
numbers in spinal segment T13 in rats.
AB - The main purpose of the present study was to investigate the effects of
diclofenac sodium (DS) on the total number of neurons in segment T13 of the
spinal cord of offspring of pregnant rats using stereological methods. Eighteen
adult female Wistar albino rats weighing 150-200g were used. Pregnant female rats
were divided into three groups; a control group, a sham group and a DS (1mg/kg,
intramuscular) exposed group. The DS and sham groups received injection from the
5th day of gestation to the 19th. Twenty eight days after birth, the offspring
rats were perfused with 4% buffered formalin. T13, which is one of transverse
spinal cord segments, were isolated and processed for routine paraffin histology.
5MUm sections were obtained using a rotary microtome according to systematic
random sampling strategies. Every 40th section was taken and sections were
stained with modified Giemsa. All types of motor neuron cell were identified
according to their morphology. In this study, the "disector-Cavalieri
combination" method was used in the stereological examination of neurons. The
motor neurons were counted in the right gray matter of the ventral horn in the
spinal cord segment. The Kruskal-Wallis test was used for comparison the groups.
In terms of motoneuron number, no significant difference among the groups was
found (p>0.05). In conclusion, our results indicated that prenatal exposure to DS
has no effect on the total number of motor neuron of the offspring rats.
PMID- 28495519
TI - The involvement of autophagy and cytoskeletal regulation in TDCIPP-induced SH
SY5Y cell differentiation.
AB - Exposure and toxicity to organophosphate-based flame retardants are an increasing
health concern. Neurons appear to be particularly vulnerable to the effects of
these chemicals. For example, in vitro studies have shown that tris(1,3-dichloro
2-propyl) phosphate (TDCIPP) induces apoptosis and autophagy in neural cells. In
the present study, we investigated the cell biological mechanisms of TDCIPP
induced neurotoxicity using undifferentiated human SH-SY5Y neuroblastoma cells as
a model. Interestingly, TDCIPP treatment promoted differentiation in SH-SY5Y
cells, which displayed various alterations including neurite elongation, an
expansion of the numbers of neurite-bearing cells, and an increase in expression
of cytoskeletal components normally enriched in neurons. Furthermore, the
upregulation of microtubule-associated protein light chain 3, the degradation of
p62/sequestosome 1, and the formation of autophagosomes occurred in treated
cells, suggesting that TDCIPP exposure induces autophagy. However, pretreatment
with the autophagy inhibitor 3-methyladenine suppressed TDCIPP-induced autophagy
and reduced expression of the aforementioned cytoskeletal components. This
correlated with a reduction in neurite outgrowth and numbers of neurite-bearing
cells. Taken together, these results indicate that autophagy might promote TDCIPP
induced SH-SY5Y cell differentiation, which leads to an increase in expression of
cytoskeletal components and neurite outgrowth. This study offers key insights
into the mechanisms of neurotoxicity associated with this commonly used
organophosphate.
PMID- 28495520
TI - Brain uptake of deltamethrin in rats as a function of plasma protein binding and
blood-brain barrier maturation.
AB - Pyrethroids, including permethrin and deltamethrin (DLM), are very widely used of
insecticides. It was hypothesized that lower plasma binding and increased blood
brain barrier (BBB) penetration of DLM in immature rats contribute to the higher
brain concentrations of DLM and more pronounced neurotoxicity reported in this
age group. The left brain of anesthetized adult rats was perfused for 2min via a
carotid artery with 1MUM 14C-DLM in: 2-5% human serum albumin (HSA); plasma from
adult and 15- and 21-d-old rats; and plasma from human donors of: birth-1 week, 1
4 weeks, 4 weeks-1 year, 1-3 years and adults. The fraction of DLM bound and
brain uptake of DLM did not vary significantly with the HSA concentration nor
with the age of rat or human plasma donors. One, 10 and 50MUM 14C-DLM were
perfused into the left-brain of anesthetized adult, 15- and 21-d-old rats. DLM
deposition in the brain was linear over this range of concentrations and
inversely related to age. The results of this investigation indicate that
increased BBB permeability in the youngest rats enhances brain deposition of the
insecticide. Plasma protein binding of DLM in immature rats and humans is not
sufficiently diminished to impact its brain uptake.
PMID- 28495521
TI - Efficacy of local glucocorticoid after local anesthetic in low back pain with
lumbosacral transitional vertebra: A randomized placebo-controlled double-blind
trial.
AB - OBJECTIVE: The primary objective of this study was to compare the efficacy of
local injection of a local anesthetic with a glucocorticoid versus a local
anesthetic with saline to treat low back pain due to lumbosacral transitional
vertebras (LSTV) with a pseudoarticulation. METHODS: A randomized placebo
controlled double-blind study was conducted in patients with unilateral low back
pain ascribed clinically to LSTV. Patients were randomized to lidocaine plus
saline (LS group) or lidocaine plus cortivazol (LC group) injected locally under
computed tomography guidance. The primary outcome measure was the 24-hour mean
visual analog scale (VAS) score for low back pain 4 weeks after the injection.
RESULTS: Of 16 randomized patients, 15 were included in the analysis, 8 in the LS
group and 7 in the LC group. The mean VAS pain score at week 4 was not
significantly different between the two groups. In the two groups pooled, the
mean VAS pain score decreased significantly from baseline to week 4, from 5.52+/
0.99 to 3.86+/-2.55 (P<=0.05). The difference remained significant at week 12.
Significant improvements occurred in the EIFEL disability index and items of the
Dallas Pain Questionnaire. No adverse events were recorded. CONCLUSION: In
patients with chronic low back pain consistent with a symptomatic LSTV type II or
IV in the Castellvi classification, a local injection of lidocaine with or
without cortivazol may provide sustained improvements in pain and function. The
underlying mechanism is unclear.
PMID- 28495522
TI - Spondyloarthritis: An expanding cast of cellular actors.
PMID- 28495523
TI - Hyaluronic acid: Still useful in knee osteoarthritis?
PMID- 28495524
TI - Granulomatosis with polyangiitis (Wegener granulomatosis): A proteinase-3 driven
disease?
AB - Granulomatosis with polyangiitis (GPA, Wegener granulomatosis) is a systemic
autoimmune vasculitis that affects small arteries, arterioles, and capillaries,
most notably in the kidneys and lungs. In this disease, proteinase-3 (PR3),
produced by neutrophils, is targeted by antineutrophil cytoplasmic antibodies
(ANCA). Recent work by our group has shown how PR3 impairs the resolution of
inflammation and deregulates the immune system. Normally, the clearance of
activated neutrophils triggers an anti-inflammatory, pro-resolution process. In
patients with GPA, however, macrophages phagocytose apoptotic neutrophils then
release massive amounts of pro-inflammatory mediators, notably interleukin-1,
thereby generating a pro-inflammatory microenvironment conducive to autoimmunity.
This deregulation of immune processes is accompanied with activation of
plasmacytoid dendritic cells and with polarization of T-helper-2 (Th2), Th9, and
Th17 cells. These recent data highlight the dual role of PR3, both auto-antigenic
and auto-inflammatory, thus potentially opening up new therapeutic avenues.
PMID- 28495526
TI - Multidrug-resistant Pseudomonas aeruginosa skin and soft-tissue infection
successfully treated with ceftolozane/tazobactam.
AB - Ceftolozane/tazobactam (C/T) is a novel beta-lactam/beta-lactamase inhibitor
combination antibiotic approved by the US Food and Drug Administration for the
treatment of complicated intra-abdominal and urinary tract infections due to Gram
negative bacteria, particularly extended-spectrum beta-lactamase-producing
Enterobacteriaceae and multidrug-resistant (MDR) Pseudomonas aeruginosa strains.
Here we report a case of MDR P. aeruginosa skin and soft-tissue infection
successfully treated with C/T.
PMID- 28495525
TI - Latent tuberculosis infection: the final frontier of tuberculosis elimination in
the USA.
AB - Since 1989, the USA has been pursuing the goal of tuberculosis elimination. After
substantial progress during the past two decades, the rate of tuberculosis cases
in the USA each year has now levelled off and remains well above the elimination
threshold. Both epidemiological data and modelling underline the necessity of
addressing latent tuberculosis infection if further progress is to be made in
eliminating the disease. In this Personal View we explore next steps towards
elimination. Given the estimated prevalence of latent tuberculosis infection,
compared with the limited testing and treatment that currently occur, a major new
effort is required. This effort should consist of a surveillance system or
registry to monitor progress, scale-up of targeted testing for latent
tuberculosis infection in at-risk populations, scale-up of short-course treatment
regimens, engagement of affected communities and medical providers who serve
those communities, and increased public health staffing for implementation and
oversight. Such an effort would benefit greatly from the development of new
tools, such as tests that better indicate reactivation risk, and even shorter
latent tuberculosis infection treatment regimens than currently exist.
PMID- 28495527
TI - Facilitating State-Wide Collaboration around Family Planning Care in the Context
of Zika.
AB - INTRODUCTION: Family planning providers have an important role to play in the
response to the public health challenge posed by Zika. In the United States,
there are high rates of unintended pregnancy, especially in states most at risk
for mosquito-borne transmission of the Zika virus. This paper describes efforts
by eight of these states (Arizona, California, Florida, Georgia, Louisiana,
Mississippi, South Carolina, and Texas) to build capacity for quality family
planning care in the context of Zika. METHODS: Drawing on resources developed by
the Office of Population Affairs, including a toolkit for family planning care in
the context of Zika, agencies and stakeholders involved in the family planning
delivery system in Southern states at risk for mosquito-borne transmission met
over several months in the summer of 2016 to coordinate efforts to respond to the
risk of Zika in their jurisdictions. RESULTS: Through proactive communication and
collaboration, states took steps to integrate Zika-related family planning care,
including screening for Zika risk and providing appropriate, client-centered
counseling. Challenges faced by the states included not having family planning
included as a component of their state's Zika response effort, limited funding
for family planning activities, and the need for robust communication networks
between multiple state and federal agencies. CONCLUSIONS: The efforts described
in this paper can help other states to integrate family planning into their Zika
response. This is relevant to all states; even when mosquito-borne transmission
is not occurring or expected, all states experience travel-related and sexually
transmitted Zika infections.
PMID- 28495528
TI - Hepatic ischemia/reperfusion injury disrupts the homeostasis of kidney primary
cilia via oxidative stress.
AB - Acute kidney injury (AKI) is a major complication of hepatic surgeries. The
primary cilium protrudes to the lumen of kidney tubules and plays an important
role in renal functions. Disruption of primary cilia homeostasis is highly
associated with human diseases including AKI. Here, we investigated whether
transient hepatic ischemia induces length change and deciliation of kidney
primary cilia, and if so, whether reactive oxygen species (ROS)/oxidative stress
regulates those. HIR induced damages to the liver and kidney with increases in
ROS/oxidative stress. HIR shortened the cilia of kidney epithelial cells and
caused them to shed into the urine. This shortening and shedding of cilia was
prevented by Mn(III) tetrakis(1-methyl-4-pyridyl) porphyrin (MnTMPyP, an
antioxidant). The urine of patient undergone liver resection contained ciliary
proteins. These findings indicate that HIR induces shortening and deciliation of
kidney primary cilia into the urine via ROS/oxidative stress, suggesting that
primary cilia is associated with HIR-induced AKI and that the presence of ciliary
proteins in the urine could be a potential indication of kidney injury.
PMID- 28495529
TI - MEK/ERK- and calcineurin/NFAT-mediated mechanism of cerebral hyperemia and brain
injury following NMDA receptor activation.
AB - N-methyl-d-aspartate (NMDA) receptor activation increases regional cerebral blood
flow (rCBF) and induces neuronal injury, but similarities between these processes
are poorly understood. In this study, by measuring rCBF in vivo, we identified a
clear correlation between cerebral hyperemia and brain injury. NMDA receptor
activation induced brain injury as a result of rCBF increase, which was
attenuated by an inhibitor of mitogen-activated protein kinase or calcineurin.
Moreover, NMDA induced phosphorylation of extracellular signal-regulated kinase
(ERK) and nuclear translocation of nuclear factor of activated T-cell (NFAT) in
neurons. Therefore, a MEK/ERK- and calcineurin/NFAT-mediated mechanism of
neurovascular coupling underlies the pathophysiology of neurovascular disorders.
PMID- 28495530
TI - Erythrocyte membrane nanoparticles improve the intestinal absorption of
paclitaxel.
AB - Paclitaxel (PTX) is a cytotoxic chemotherapy drug with encouraging activity in
human malignancies. However, free PTX has a very low oral bioavailability due to
its low aqueous solubility and the gastrointestinal drug barrier. In order to
overcome this obstacle, we have designed erythrocyte membrane nanoparticles
(EMNP) using sonication method. The permeability of PTX by EMNP was 3.5-fold
(Papp = 0.425 nm/s) and 16.2-fold (Papp = 394.1 nm/s) higher than free PTX in
MDCK-MDR1 cell monolayers and intestinal mucosal tissue, respectively. The in
vivo pharmacokinetics indicated that the AUC0-t (MUg/mL.h) and Cmax (MUg/mL) of
EMNP were 14.2-fold and 6.0-fold higher than that of free PTX, respectively. In
summary, the EMNP appears to be a promising nanoformulation to enhance the oral
bioavailability of insoluble and poorly permeable drugs.
PMID- 28495531
TI - The forkhead-like transcription factor (Fhl1p) maintains yeast replicative
lifespan by regulating ribonucleotide reductase 1 (RNR1) gene transcription.
AB - In eukaryotes, numerous genetic factors contribute to the lifespan including
metabolic enzymes, signal transducers, and transcription factors. As previously
reported, the forkhead-like transcription factor (FHL1) gene was required for
yeast replicative lifespan and cell proliferation. To determine how Fhl1p
regulates the lifespan, we performed a DNA microarray analysis of a heterozygous
diploid strain deleted for FHL1. We discovered numerous Fhl1p-target genes, which
were then screened for lifespan-regulating activity. We identified the
ribonucleotide reductase (RNR) 1 gene (RNR1) as a regulator of replicative
lifespan. RNR1 encodes a large subunit of the RNR complex, which consists of two
large (Rnr1p/Rnr3p) and two small (Rnr2p/Rnr4p) subunits. Heterozygous deletion
of FHL1 reduced transcription of RNR1 and RNR3, but not RNR2 and RNR4. Chromatin
immunoprecipitation showed that Fhl1p binds to the promoter regions of RNR1 and
RNR3. Cells harboring an RNR1 deletion or an rnr1-C428A mutation, which abolishes
RNR catalytic activity, exhibited a short lifespan. In contrast, cells with a
deletion of the other RNR genes had a normal lifespan. Overexpression of RNR1,
but not RNR3, restored the lifespan of the heterozygous FHL1 mutant to the wild
type (WT) level. The Deltafhl1/FHL1 mutant conferred a decrease in dNTP levels
and an increase in hydroxyurea (HU) sensitivity. These findings reveal that Fhl1p
regulates RNR1 gene transcription to maintain dNTP levels, thus modulating
longevity by protection against replication stress.
PMID- 28495533
TI - MicroRNA-27a reduces mutant hutingtin aggregation in an in vitro model of
Huntington's disease.
AB - Huntington's disease (HD) is a fatal genetic disease caused by abnormal
aggregation of mutant huntingtin protein (mHtt). Reduction of mHtt aggregation
decreases cell death of the brain and is a promising therapeutic strategy of HD.
MicroRNAs are short non-coding nucleotides which modulate various genes and
dysregulated in many diseases including HD. MicroRNA miR-27a was reported to be
reduced in the brain of R6/2 HD mouse model and modulate multidrug resistance
protein-1 (MDR-1). Using subventricular zone-derived neuronal stem cells (NSCs),
we used in vitro HD model to test the effect of miR-27a on MDR-1 and mHtt
aggregation. R6/2-derived NSCs can be differentiated under condition of growth
factor deprivation, and the progression of differentiation leads to a decrease of
MDR-1 level and efflux function of cells. Immunocytochemistry result also
confirmed that mHtt aggregation was increased with differentiation. We
transfected miR-27a in the R6/2-derived differentiated NSCs, and examined
phenotype of HD, mHtt aggregation. As a result, miR-27a transfection resulted in
reduction of mHtt aggregation in HD cells. In addition, MDR-1, which can
transport mHtt, protein level was increased by miR-27a transfection. Conversely,
knock-down of MDR-1 through MDR-1 siRNA increased mHtt aggregation in vitro. Our
results indicate that miR-27a could reduce mHtt level of the HD cell by
augmenting MDR-1 function.
PMID- 28495534
TI - Hybrid Treatment of the Aberrant Right Subclavian Artery (Arteria Lusoria):
Feasibility Study on 180 Angio-CTs.
AB - BACKGROUND: The aberrant right subclavian artery or arteria lusoria (AL) is the
most frequent anatomical variation of the supra-aortic trunks (SAT). Treatment is
only warranted in the presence of an aneurysm because of the risk of rupture, or
in symptomatic cases with signs of compression of the esophagus or the trachea,
with embolisms causing right upper limb ischemia of vertebrobasilar
cerebrovascular accidents. The conventional surgical treatment of AL is the
closure of the origin of AL and the revascularization of the right subclavian
artery through a left thoracotomy. With the appearance of endovascular
techniques, some of these patients can be treated with minimally invasive hybrid
techniques. The aim of this study is to evaluate the feasibility of the
endovascular treatment of AL based on the radioanatomical analysis of the
thoracic angio-computed tomographies. METHODS: We analyzed 180 thoracic angio
computed tomographies using millimeter cuts (<1.2 mm) performed between 2010 and
2015 in the Nancy University Hospital in which an AL was fortuitously discovered.
Symptomatic ALs and pediatric patients were excluded. The diameters of the SATs
and the aorta and the distances between the SATs were measured. The data were
processed with the t-test using the SPSS 22 software. RESULTS: Our results showed
the presence of a Kommerell diverticulum in 36 cases (20%) and of a bi-carotid
trunk in 91 cases (50.5%). The average distance between the left subclavian
artery (LSCA) and AL was 5.4 +/- 4.3 mm. To obtain a proximal neck >20 mm for the
implantation of a thoracic stent graft, a double transposition or bypass was
always necessary (LSCA to left common carotid artery, AL to right common
carotid). An additional debranching of the left common carotid artery was
necessary in 33.8% of the cases and of all the SATs in 2.9% of the cases.
CONCLUSIONS: The radio-anatomical study showed that no patient was eligible for
conventional thoracic endovascular aneurysm repair to treat an aneurysmal AL. The
hybrid approach is feasible using a double transposition or a bypass before the
implantation of a stent graft, if needed associated with a debranching of the
common carotid arteries.
PMID- 28495532
TI - New insights into the role of mitochondrial calcium homeostasis in cell
migration.
AB - Mitochondria are dynamic organelles involved in numerous physiological functions.
Beyond their function in ATP production, mitochondria regulate cell death,
reactive oxygen species (ROS) generation, immunity and metabolism. Mitochondria
also play a key role in the buffering of cytosolic calcium, and calcium
transported into the matrix regulates mitochondrial metabolism. Recently, the
identification of the mitochondrial calcium uniporter (MCU) and associated
regulators has allowed the characterization of new physiological roles for
calcium in both mitochondrial and cellular homeostasis. Indeed, recent work has
highlighted the importance of mitochondrial calcium homeostasis in regulating
cell migration. Cell migration is a property common to all metazoans and is
critical to embryogenesis, cancer progression, wound-healing and immune
surveillance. Previous work has established that cytoplasmic calcium is a key
regulator of cell migration, as oscillations in cytosolic calcium activate
cytoskeletal remodelling, actin contraction and focal adhesion (FA) turnover
necessary for cell movement. Recent work using animal models and in cellulo
experiments to genetically modulate MCU and partners have shed new light on the
role of mitochondrial calcium dynamics in cytoskeletal remodelling through the
modulation of ATP and ROS production, as well as intracellular calcium
signalling. This review focuses on MCU and its regulators in cell migration
during physiological and pathophysiological processes including development and
cancer. We also present hypotheses to explain the molecular mechanisms by which
MCU may regulate mitochondrial dynamics and motility to drive cell migration.
PMID- 28495535
TI - Endoluminal Dilation Technique to Remove Stuck Port-A-Cath: A Case Report.
AB - Port-a-cath is a type of central venous catheter (CVC) designed to allow repeated
access to the venous system for parenteral delivery of medications, fluids, and
nutritional solutions and for sampling venous blood. After years of use or in
case of damage, CVC must be removed and eventually replaced: the recovery of the
device should normally be easy, with a small surgical incision of the skin and
tissues surrounding the device and pulling the catheter. Sometimes, scar tissue
can develop around the device, making it resistant to removal even after
application of forceful traction. We report a case of stuck port-a-cath that was
extracted by using endoluminal dilatation technique.
PMID- 28495536
TI - Neoaortoiliac System Procedure to Treat Infected Aortic Grafts.
AB - BACKGROUND: The aim of this case series is to report the results of our center in
the surgical treatment of infected abdominal aortic grafts using the
neoaortoiliac system (NAIS) procedure. METHODS: Four male and 2 female patients
underwent an NAIS repair after endovascular (n = 3), open (n = 2), or combined
surgery (n = 1) in our center. Mean age was 73 +/- 5.2 years. Graft infection was
diagnosed by computed tomography angiography (CTA), and only in 2 cases further
imaging was necessary. The diagnosis was set at average 6.2 years after the
initial procedure. RESULTS: Four patients underwent a standard pantaloon NAIS
procedure, 1 patient with a small aortic diameter received 1 femoral vein as
aortoaortic interposition graft, and 1 patient received a unilateral aortoiliac
bypass; all patients received autologous femoral veins grafts. Thirty-day
mortality was zero, with in-hospital mortality of 1 patient (16.7%). Mean
hospital stay was 27 +/- 4.9 days, with mean intensive care unit stay of 2.2 days
(range: 1-3). During follow-up (mean: 6.17 months, range: 1-24 months), 2
patients presented with thigh wound complications, one of which required surgical
revision. One patient was readmitted due to upper gastrointestinal (GI) bleeding
as a side effect of anticoagulation, without the presence of ulcer or other GI
pathology. CONCLUSIONS: In our early experience, NAIS showed to be a demanding
procedure for both the patient and the surgical team. It avoids however the
disadvantages of extra-anatomic bypass and other methods used to treat aortic
graft infection. Larger study groups are necessary to support these findings.
PMID- 28495537
TI - Impact of Nutritional State on Critical Limb Ischemia Early Outcomes (DENUCRITICC
Study).
AB - BACKGROUND: Despite current progress, the prognosis of critical limb ischemia
(CLI) remains poor. The ageing of the population, the increasing prevalence of
diabetes mellitus, and the stability of tobacco use will increase the prevalence
of CLI. CLI patients have risk factors for malnutrition, and the impact of
malnutrition on morbidity and mortality has been demonstrated in the general
population. However, we have little information on the consequences of
undernutrition in the CLI population. The aim of this study is to assess the
impact of malnutrition on the early outcomes in CLI patients. METHODS: This is a
double-center prospective study that included all consecutive hospitalized
patients with CLI. All patients were screened for malnutrition and divided into 2
groups: severe malnourished patients (group A) and moderate malnourished and well
nourished (group B). This distribution was based on age-indexed clinical and
biological data and the patient's general condition: the Nutritional Risk Index
for patients younger than 75 years, the Mini Nutritional Assessment, or the
Geriatric Nutritional Risk Index for those older than 75 years. The primary end
point was defined as the rate of 30-day death. Outcomes were compared in a
univariate analysis. Stepwise logistic regression was used for the multivariate
analysis. Variables with a P value <0.2 in the univariate analysis were
introduced in the multivariate model. RESULTS: We included 106 patients. The
prevalence of malnutrition was 75.5%, divided into moderate malnutrition (51.9%)
and severe malnutrition (23.6%). Six patients (24%) died in group A compared with
8 in group B (4.9%) (P = 0.01). By univariate analysis, severe malnutrition was
the only factor associated with death at 30 days. By stepwise logistic
regression, severe malnutrition (odds ratio 6.1, 95% confidence interval 1.6
23.7, P = 0.006) was found to be the significant risk factors for death at 30
days. CONCLUSIONS: This study is the first to demonstrate prospectively the major
importance of malnutrition in the early prognosis of CLI patients.
PMID- 28495538
TI - Clinical Outcome of Carotid Artery Stenting According to Provider Specialty and
Volume.
AB - BACKGROUND: Several studies have demonstrated better outcomes for carotid
endarterectomy with high-volume hospitals and providers. However, only a few
studies have reported on the impact of operator specialty/volume on the
perioperative outcome of carotid artery stenting (CAS). This study will analyze
the correlation of CAS outcomes and provider specialty and volume. METHODS:
Prospectively collected data of CAS procedures done at our institution during a
10-year period were analyzed. Major adverse events (MAEs; 30-day stroke,
myocardial infarction, and death) were compared according to provider specialty
(vascular surgeons [VSs], interventional cardiologists [ICs], interventional
radiologists [IRs], interventional vascular medicine [IVM]), and volume (>=5
CAS/year vs. <5 CAS/year). RESULTS: Four hundred fourteen CAS procedures (44% for
symptomatic indications) were analyzed. Demographics/clinical characteristics
were somewhat similar between specialties. MAE rates were not significantly
different between various specialties: 3.1% for IC, 6.3% for VS, 7.1% for IR,
6.7% for IVM (P = 0.3121; 6.3% for VS and 3.8% for others combined, P = 0.2469).
When physicians with <5 CAS/year were excluded: the MAE rates were 3.1% for IC,
4.7% for VS, and 6.7% for IVM (P = 0.5633). When VS alone were compared with
others, and physicians with <5 CAS/year were excluded, the MAE rates were 4.7%
for VS vs. 3.6% for non-VS (P = 0.5958). The MAE rates for low-volume providers,
regardless of their specialty, were 9.5% vs. 4% for high-volume providers (P =
0.1002). Logistic regression analysis showed that the odds ratio of MAE was 0.4
(0.15-1.1, P = 0.0674) for high-volume providers, while the odds ratio for VS was
1.3 (0.45-3.954, P = 0.5969). CONCLUSIONS: Perioperative MAE rates for CAS were
similar between various providers, regardless of specialties, particularly for
vascular surgeons with similar volume to nonvascular surgeons. Low-volume
providers had higher MAE rates.
PMID- 28495539
TI - Ureteroarterial Fistulas: Diagnosis, Management, and Clinical Evolution.
AB - BACKGROUND: Ureteroarterial fistulas (UAFs) have a low incidence but are a
potentially fatal cause of hematuria. Initially treated by open surgery,
endovascular techniques have decreased potential complications. MATERIAL AND
METHODS: We present a short series of UAFs (n = 5) treated in our institution in
the last 10 years: 1 case showed up after aorta-iliac bypass surgery, 1 case
after endovascular aortic repair and embolization of right hypogastric artery,
and 3 cases after oncological surgeries. We review the published literature via
PubMed. RESULTS: The different approaches (2 open and 3 endovascular procedures)
were based on the clinical situation of the patients and on technical
limitations. Three patients died after the procedure (2 after open surgery and 1
after endovascular treatment). In our institution, endovascular treatment showed
good results in terms of early complications and associated mortality compared
with open surgery. CONCLUSIONS: UAF is a rare but a potentially fatal
complication in patients with predisposing factors. No long-term follow-up has
been published to assess the possible complications arising from the technique,
such as prosthetic infection. No antibiotic treatment protocols have been
established, so long-term follow-up is necessary to determine late complications.
PMID- 28495540
TI - Results of the French Multicentric Study of ANACONDATM Fenestrated Endografts in
the Treatment of Complex Aortic Pathologies (EFEFA Registry).
AB - BACKGROUND: Most of the experience on fenestrated endovascular aneurysm repair
involves the custom-made Zenith(r) endograft (Cook). The fenestrated Anaconda(r)
endograft (Vascutek) was introduced with the potential advantages of complete
repositioning and lack of stent material on the main aortic body for more
versatility. However, few data are available. Our objective was to assess its mid
term results in the treatment of complex aortic aneurysms. METHODS: Consecutive
patients treated with the custom-made fenestrated Anaconda endograft in France
and the Principality of Monaco, from December 2010 to October 2015, were
included. RESULTS: Eighty-six patients were included over 16 centers (82 men,
mean age 73.4 +/- 8.1 years, 16 (18.6%) symptomatic aneurysms). The repositioning
system was used in 68 cases (79.1%). Two hundred ninety-two visceral/renal
vessels were targeted, with a mean number of 3.4 +/- 0.6 target vessels/patient
and a successful reconstruction in 99.3% of the cases (290/292 vessels).
Perioperative technical success was achieved in 86.0% (74/86 patients). In
hospital and 30-day mortality rates were 3.5% (3 patients) and 7.0% (6 patients),
respectively. At 12 and 24 months, estimated overall survival rate was 88.3% and
85.2%, target vessel's patency rate was 97.2% and 96.3%, and freedom from
aneurysm-related reintervention rate was 96.3% and 88.0%, respectively. At 24
months, there were 7 type II endoleaks (12.7%) and a significant reduction in
aneurysm maximum transverse diameter in 70.4%. Five limb occlusions occurred at 1
year and 1 at 2-year follow-up (7.0%). CONCLUSIONS: The fenestrated Anaconda
stent-graft system offers acceptable technical success rates, mid-term efficacy,
and durability with respect to aneurysm sac regression, target vessel patency,
overall mortality, and reintervention rates. Long-term results are still awaited,
until then, the rate of graft limb occlusion is of concern and should be further
investigated, especially in case of particularly complex aortic anatomies.
PMID- 28495541
TI - Endovascular Repair of a Short Neck Abdominal Aortic Aneurysm with a Physician
Modified Vascutek Anaconda Stent Graft.
AB - An 81-year-old woman was referred for the treatment of a 79-mm-diameter short
neck abdominal aortic aneurysm with highly tortuous iliac arteries. She was
considered at high risk for open repair and not suitable for standard
endovascular repair given the short length of the proximal neck. Delay for a
manufactured custom-made fenestrated stent graft was too long given the diameter
of the aneurysm. A flexible stent graft was preferred because of severe iliac
tortuosity. Endovascular repair was performed using a physician-modified Anaconda
stent graft with 1 fenestration for the left renal artery. The technique for
device modification and implantation is described. Postoperative course was
uneventful and 1-year computed tomography scan showed complete exclusion of the
aneurysm sac and patent left renal artery.
PMID- 28495542
TI - Endothelial Function Is Preserved in Veins Harvested by Either Endoscopic or
Surgical Techniques.
AB - BACKGROUND: Endoscopic vein harvest for lower extremity arterial bypass grafting
has been questioned due to concern for endothelial damage during procurement. We
sought to compare nitric oxide (NO)-mediated endothelial-dependent relaxation
(EDR) in vein segments harvested using open surgical techniques (OH) versus
endoscopic vein harvest (EH) techniques. METHODS: Saphenous vein segments were
harvested for lower extremity bypass, and a single, minimally handled section of
saphenous vein, free of branches, was taken from the end of the graft. Four 4-mm
venous ring segments were then cut and mounted on force transducers. Segments
were mounted in 37 degrees oxygenated Krebs-Henseleit solution and maximally
contracted using KCl. Individual ring segments that did not react to KCl were
excluded from the study. Norepinephrine (NE) was used to achieve submaximal
contraction. EDR was determined using increasing concentrations of bradykinin
(BDK). Endothelial-independent relaxation (EIR) was confirmed using sodium
nitroprusside. Two-way analysis of variance (ANOVA) was used to analyze
differences between harvest techniques across BDK concentration and a Student's t
test was used to analyze single comparisons. RESULTS: Vein segments harvested
from patients (n = 13) led to 28 viable rings that exhibited a positive reaction
to KCl (11 rings; 5 patients EH vs. 17 rings; 8 patients OH). Both vein groups
achieved moderate relaxation to maximal BDK concentration, [10-6 M]; (49.5% EH
vs. 40.55% OH, P = 0.270). Analysis by 2-way ANOVA for mean % relaxation for BDK
concentration [10-11-10-6 M] showed improved EDR in EH samples compared with OH
(P = 0.029). Mean nitrite/nitrate (NO(x)) tissue bath concentration measurements
post-BDK were 139.8 nM (EH) vs. 97.2 nM (OH; P = 0.264). Histology and positive
factor VIII immunohistochemistry staining provided evidence for the presence of
intact endothelium in our sample segments. EIR was preserved and was similar in
the two groups. CONCLUSIONS: Endothelial function is preserved when utilizing
endoscopic harvesting techniques. The advantages of minimally invasive vein
procurement for lower extremity bypass can be obtained without concern for
damaging venous endothelium.
PMID- 28495543
TI - Trans-pericardal Color Doppler Ultra Sound to Assess Blood Flow in the Visceral
Branches during Type A Dissection Procedures Complicated with Mesenteric
Malperfusion.
AB - Aortic dissection is a complex disease associated with high mortality and
morbidity. Among the different possible clinical presentations, type A aortic
dissection complicated at the onset by mesenteric malperfusion is characterized
by poor outcome compared with patients not presenting such complication. We
report the case of a patient with acute type A aortic dissection presenting with
mesenteric malperfusion, in whom trans-pericardial color Doppler ultrasound
(CDUS) examination was used to assess intraoperative and postoperative blood flow
in the mesenteric artery. Trans-pericardial CDUS is demonstrated as a fast and
simple diagnostic method with a good matching compared with contrast-enhanced
computed tomography scan imaging, if correctly approached. We believe that this
technique could be an important adjunctive tool for the intraoperative and
perioperative management and decision-making in all patients with type A
dissection presenting with mesenteric ischemia.
PMID- 28495545
TI - Asymptotic tracking and disturbance rejection of the blood glucose regulation
system.
AB - Type 1 diabetes patients need external insulin to maintain blood glucose within a
narrow range from 65 to 108 mg/dl (3.6 to 6.0 mmol/l). A mathematical model for
the blood glucose regulation is required for integrating a glucose monitoring
system into insulin pump technology to form a closed-loop insulin delivery system
on the feedback of the blood glucose, the so-called "artificial pancreas". The
objective of this paper is to treat the exogenous glucose from food as a glucose
disturbance and then develop a closed-loop feedback and feedforward control
system for the blood glucose regulation system subject to the exogenous glucose
disturbance. For this, a mathematical model for the glucose disturbance is
proposed on the basis of experimental data, and then incorporated into an
existing blood glucose regulation model. Because all the eigenvalues of the
disturbance model have zero real parts, the center manifold theory is used to
establish blood glucose regulator equations. We then use their solutions to
synthesize a required feedback and feedforward controller to reject the
disturbance and asymptotically track a constant glucose reference of 90 mg/dl.
Since the regulator equations are nonlinear partial differential equations and
usually impossible to solve analytically, a linear approximation solution is
obtained. Our numerical simulations show that, under the linear approximate
feedback and feedforward controller, the blood glucose asymptotically tracks its
desired level of 90 mg/dl approximately.
PMID- 28495544
TI - Modeling glucose metabolism and lactate production in the kidney.
AB - The metabolism of glucose provides most of the ATP required for energy-dependent
transport processes. In the inner medulla of the mammalian kidney, limited blood
flow and O2 supply yield low oxygen tension; therefore, a substantial fraction of
the glucose metabolism in that region is anaerobic. Lactate is considered to be a
waste product of anaerobic glycolysis, which yields two lactate molecules for
each glucose molecule consumed, thereby likely leading to the production and
accumulation of a significant amount of lactate in the inner medulla. To gain
insights into the transport and metabolic processes in the kidney, we have
developed a detailed mathematical model of the renal medulla of the rat kidney.
The model represents the radial organization of the renal tubules and vessels,
which centers around the vascular bundles in the outer medulla and around
clusters of collecting ducts in the inner medulla. Model simulations yield
significant radial gradients in interstitial fluid oxygen tension and glucose and
lactate concentrations in the outer medulla and upper inner medulla. In the deep
inner medulla, interstitial fluid concentrations become much more homogeneous, as
the radial organization of tubules and vessels is not distinguishable. Using this
model, we have identified parameters concerning glucose transport and basal
metabolism, as well as lactate production via anaerobic glycolysis, that yield
predicted blood glucose and lactate concentrations consistent with experimental
measurements in the papillary tip. In addition, simulations indicate that the
radial organization of the rat kidney may affect lactate buildup in the inner
medulla.
PMID- 28495546
TI - Subcortical brain volume differences in participants with attention deficit
hyperactivity disorder in children and adults.
PMID- 28495547
TI - Corrections.
PMID- 28495548
TI - Subcortical brain volume differences in participants with attention deficit
hyperactivity disorder in children and adults - Authors' reply.
PMID- 28495550
TI - Subcortical brain volume differences in participants with attention deficit
hyperactivity disorder in children and adults.
PMID- 28495549
TI - A blind spot on the global mental health map: a scoping review of 25 years'
development of mental health care for people with severe mental illnesses in
central and eastern Europe.
AB - Just over 25 years have passed since the major sociopolitical changes in central
and eastern Europe; our aim was to map and analyse the development of mental
health-care practice for people with severe mental illnesses in this region since
then. A scoping review was complemented by an expert survey in 24 countries.
Mental health-care practice in the region differs greatly across as well as
within individual countries. National policies often exist but reforms remain
mostly in the realm of aspiration. Services are predominantly based in
psychiatric hospitals. Decision making on resource allocation is not transparent,
and full economic evaluations of complex interventions and rigorous
epidemiological studies are lacking. Stigma seems to be higher than in other
European countries, but consideration of human rights and user involvement are
increasing. The region has seen respectable development, which happened because
of grassroots initiatives supported by international organisations, rather than
by systematic implementation of government policies.
PMID- 28495551
TI - Subcortical brain volume differences in participants with attention deficit
hyperactivity disorder in children and adults.
PMID- 28495552
TI - Subcortical brain volume differences in participants with attention deficit
hyperactivity disorder in children and adults.
PMID- 28495554
TI - Collecting duct carcinoma of the kidney: Disease characteristics and treatment
outcomes from the National Cancer Database.
AB - OBJECTIVE: To use a large population-level database to assess survival outcomes
for collecting duct renal cell carcinoma (CDRCC). MATERIALS AND METHODS: The
National Cancer Database was queried for all cases of CDRCC and clear cell renal
cell carcinoma (CCRCC) from 2004 to 2013. After removing patients with other
cancer diagnoses, the analytic cohort was composed of 201,686 CCRCC and 577 CDRCC
cases. Kaplan-Meier and cox proportional hazards analysis were employed to model
survival. RESULTS: Compared to CCRCC, patients with CDRCC presented with higher
grade and stage, node positive, and metastatic disease (70.7% vs. 30.0% with
metastasis; P<0.001). Overall median survival for CDRCC was 13.2 months (95% CI:
11.0-15.5) compared to the 122.5 months (95% CI: 121.0-123.9) for CCRCC. On
multivariate analysis of the CDRCC cohort, increasing T stage, high-grade
disease, and metastasis were predictors of mortality. Of 184 patients with
metastatic CDRCC, 113 underwent cytoreductive nephrectomy (CNx) whereas the rest
were treated with chemo/radiation or observed. Survival outcomes were improved in
patients who received both CNx with chemo/radiation compared to CNx alone (hazard
ratio = 0.51, 95% CI: 0.32-0.79) or chemo/radiation alone (hazard ratio = 0.57,
95% CI: 0.37-0.89) on multivariate analysis. CONCLUSION: CDRCC is an aggressive
subtype of renal cell carcinoma. Median survival is 13 months after diagnosis,
drastically lower than for CCRCC. More than 70% of patients have metastatic
disease at diagnosis. Chemo/radiation in addition to CNx is associated with a
survival benefit over single mode therapy.
PMID- 28495553
TI - The expanding repertoire of targets for immune checkpoint inhibition in bladder
cancer: What lies beneath the tip of the iceberg, PD-L1.
AB - Over the last decade, a new understanding of tumor-immune system interplay has
been ushered in, lead in large part by the discovery of immune checkpoints
mediated through B7-CD28 family interactions. Therapeutic blockade of the PD-L1
immune checkpoint pathway has already shown great success as a cancer
immunotherapy for advanced urothelial carcinoma, leading to durable clinical
remissions in an otherwise incurable disease. There are newly described members
of the B7-CD28 family including B7-H3, B7x, and HHLA2. These ligands are thought
to play an essential role in suppressing T-cell response, leading to immune
tolerance of tumors. This feature makes them attractive targets for novel
immunotherapy treatment paradigms. Here, we review the literature of current
strategies and future directions of immune checkpoint blockade therapy for
bladder cancer.
PMID- 28495555
TI - Oncological and functional outcomes of sexual function-preserving cystectomy
compared with standard radical cystectomy in men: A systematic review.
AB - INTRODUCTION: Different sexual function-preserving surgical techniques aimed at
improving voiding and sexual function in patients undergoing radical cystectomy
for bladder cancer have been described. The objective of this systematic review
is to determine the effect of sexual function-preserving cystectomy (SPC) on
functional and oncological outcomes. MATERIALS AND METHODS: Relevant databases
were searched covering the time frame 2000 to 2015. All publications presenting
data on any type of SPC reporting oncological or functional outcomes with a
minimum follow-up of 1 year were identified. Comparative studies including a
minimum of 30 patients and single-arm case series with a minimum of 50 patients
were selected. No language restrictions were applied. RESULTS: In a total of
8,517 identified abstracts, 12 studies were eligible for inclusion. SPC described
included prostate-, capsule-, seminal vesicle, and nerve-sparing techniques.
Local recurrence ranged from 1.2% to 61.1% (vs. 16.0%-55.0% in the control group)
and metastatic disease from 0% to 33.3% (vs. 33.0%). No differences were found in
comparative studies reporting oncological outcomes. Postoperative potency was
significantly better in the SPC groups in 6 studies comparing sexual function
preserving cystectomy vs. radical cystectomy (P<0.05). No major effect on
continence was found. Overall, there was moderate to high risk of bias and
confounding. CONCLUSIONS: The evidence base for prostate-, capsule-, or nerve
sparing cystectomy suggests that these procedures may yield better sexual
outcomes than standard cystectomy, without compromising oncological outcomes.
However, the overall quality of the evidence was moderate, and hence if offered,
patients must be carefully selected, counseled, and closely monitored.
PMID- 28495556
TI - Synthesis, crystal structure determination, biological screening and docking
studies of N1-substituted derivatives of 2,3-dihydroquinazolin-4(1H)-one as
inhibitors of cholinesterases.
AB - Pursuing the strategy of developing potent AChE inhibitors, we attempted to carry
out the N1-substitution of 2,3-dihydroquinazolin-4(1H)-one core. A set of 32 N
alkylated/benzylated quinazoline derivatives were synthesized, characterized and
evaluated for their inhibition against cholinesterases. N-alkylation of the
series of the compounds reported previously (N-unsubstituted) resulted in
improved activity. All the compounds showed inhibition of both enzymes in the
micromolar to submicromolar range. Structure activity relationship (SAR) of the
32 derivatives showed that N-benzylated compounds possess good activity than N
alkylated compounds. N-benzylated compounds 2ad and 2af were found very active
with their IC50 values toward AChE in submicromolar range (0.8uM and 0.6uM
respectively). Binding modes of the synthesized compounds were explored by using
GOLD (Genetic Optimization for Ligand Docking) suit v5.4.1. Computational
predictions of ADMET studies reveal that all the compounds have good
pharmacokinetic properties with no AMES toxicity and carcinogenicity. Moreover,
all the compounds are predicted to be absorbed in human intestine and also have
the ability to cross blood brain barrier. Overall, the synthesized compounds have
established a structural foundation for the design of new inhibitors of
cholinesterase.
PMID- 28495557
TI - DNA fluorescent labeling with naphtho[1,2,3-cd]indol-6(2H)-one for investigation
of protein-DNA interactions.
AB - Fluorescently labeled DNA to study protein-DNA interactions was synthesized using
the Cu(I)-catalysed cycloaddition (CuAAC) reaction. For this purpose, a new azido
containing fluorophore based on the naphtho[1,2,3-cd]indol-6(2H)-one derivative
was obtained. The fluorescent properties of naphtho[1,2,3-cd]indol-6(2H)-one
derivatives and labeled DNA were studied. The new fluorescent DNA conjugate was
shown to be a useful tool to study complex mechanisms of protein-DNA
interactions.
PMID- 28495558
TI - Acute psychosocial stress and everyday moral decision-making in young healthy
men: The impact of cortisol.
AB - In everyday life, moral decisions must frequently be made under acute stress.
Although there is increasing evidence that both stress and cortisol affect moral
judgment and behavior as well as decision-making in various domains unrelated to
morality, surprisingly few attempts have been made to explore the effects of
stress on everyday moral decision-making. Therefore, in the present study, we
exposed 50 young healthy men to the Trier Social Stress Test (TSST) or its non
stressful placebo version (PTSST). We investigated the impact of acute stress
exposure and stress-related cortisol levels on decision-making, decision
certainty, and emotions in 28 everyday moral conflict situations with altruistic
versus egoistic response alternatives. Results showed that the TSST-exposed group
made more altruistic decisions than the non-stress control group, while groups
did not differ in decision certainty and emotion ratings. Moreover, in
correlational as well as regression analyses, additionally controlling for
confounding variables, we observed significant positive associations between
cortisol levels and altruistic decision-making. Further analyses revealed that
altruistic decisions came along with significantly higher decision certainty and
significantly more positive emotion ratings than egoistic decisions. Notably, our
data also raise the idea that the personality trait agreeableness plays an
important role in everyday moral decision-making. In sum, our findings provide
initial evidence that both acute stress exposure and cortisol levels have
prosocial effects on everyday moral decision-making in young healthy men.
PMID- 28495560
TI - Characterization of two cryptic plasmids from Kocuria palustris IPUFS-1 and
construction of novel Escherichia coli-Kocuria shuttle vector for biocatalysis.
AB - Two cryptic plasmids, designated pKPAL1 and pKPAL2, were identified from the gram
positive bacterium Kocuria palustris IPUFS-1, which was isolated from a fish
source. The 2251-bp and 2488-bp circular genomes of pKPAL1 and pKPAL2,
respectively, were sequenced. Subsequent open reading frame (ORF) and homology
search analyses suggested that pKPAL1 and pKPAL2 possess two and three ORFs,
respectively, and encode the putative replication proteins, RepA and RepB, like
the genomes of several plasmids in gram-positive bacteria. Thus, pKPAL1 and
pKPAL2 were inferred to belong to the ColE2 plasmid family. We constructed novel
Escherichia coli-Kocuria shuttle vectors pKITE101-103 based on pKPAL1. The
constructed shuttle vector was stably maintained in Kocuria transformant cells,
and vector copy number was estimated to be about 60 per cell. Leifsonia sp. S749
alcohol dehydrogenase (LSADH) was efficiently expressed in Kocuria rhizophila
DC2201 using the pKITE103P vector under the control of the promoter of
glyceraldehyde 3-phosphate dehydrogenase (gapdh). Herein, we demonstrate that the
novel shuttle vector is a useful tool for developing biocatalysts based on
organic solvent-tolerant Kocuria cells.
PMID- 28495559
TI - Influence of adhesive strategy on clinical parameters in cervical restorations: A
systematic review and meta-analysis.
AB - OBJECTIVES: We aimed to answer the following PICO question: "Is the risk of
postoperative sensitivity (POS), retention rates and marginal discoloration of
composite restorations [CR] bonded with self-etch (SE) in non-carious cervical
lesions (NCCLs) of adults equals to etch-and-rinse (ER) adhesives?". METHODS: A
comprehensive search was performed in May 2016 in the MEDLINE, Scopus, Web of
Science, LILACS, BBO and Cochrane Library and SIGLE, abstracts of IADR,
unpublished and ongoing trials registries, dissertations and theses without
restrictions. Only randomized clinical trials that compared composite resin
restorations placed with self-etch and etch-and-rinse in NCCLs were included.
After removal of duplicates and non-eligible articles, 50 articles from 42
studies (follow-ups of the same study were merged) remained for synthesis of the
risk of bias (Cochrane Risk of bias tool). RESULTS: Thirteen studies were at
"high" risk of bias, yielding 29 studies for meta-analysis. No difference on the
POS after restoration placement (risk ratio [RR] 1.04; 95% CI 0.81 to 1.34) as
well as in the retention rates for all follow-up periods was observed. The etch
and-rinse approach produced less marginal discoloration at 18 months to 2 years
(RR 1.51; 95% CI 1.21 to 1.90) and at 4 to 5 years (RR 1.81; 95% CI 1.28 to 2.55)
(p<0.0007). CONCLUSIONS: The adhesive strategy did not influence the POS and the
retention rates of composite resin in NCCLs in any of the follow-up periods; but
less marginal discoloration was found in etch-and-rinse adhesives. CLINICAL
SIGNIFICANCE: Composite resin restorations placed with self-etch and etch-and
rinse adhesives produce restoration with the similar clinical service and POS,
however using etch-and-rinse adhesives one can reduce marginal discoloration.
PROSPERO registration number: CRD42015019533.
PMID- 28495561
TI - Function of a thermophilic archaeal chaperonin is enhanced by electrostatic
interactions with its targets.
AB - Molecular chaperonin CpkB from Thermococcus kodakarensis possesses a unique
negatively charged carboxy-terminal region that functions in target protein
recognition. In the present study, green fluorescent protein (GFP), 4
oxalocrotonate tautomerase (4OTA) and glutamine:fructose-6-phosphate
amidotransferase (GFAT) were fused with a positively charged tag, selected using
docking simulation in silico, to enhance their electrostatic interactions with
CpkB. Target proteins were heated at 75 degrees C in the presence or absence of
CpkB, and the remaining enzymatic activity was measured. The half-life (t1/2) of
the positively charged tagged targets was significantly longer than that of their
tagless counterparts. Escherichia coli cell extracts containing heterologously
expressed targets (GFP, 4OTA and GFAT and their tagged variants) were incubated
at 75 degrees C in the presence or absence of CpkB, and the proportion remaining
in the soluble fraction was evaluated by SDS-PAGE. Only positively charged tagged
targets remained predominantly in the soluble fraction in the presence of CpkB
but not in the absence of CpkB. When tagless or negatively charged tagged targets
were employed, the targets were barely detected in the soluble fraction,
suggesting that CpkB protected positively charged tagged proteins more
efficiently than tagless targets. Attachment of a positively charged tag may be a
generally applicable method for enhancing target recognition by chaperonins
carrying negatively charged carboxy-terminal regions, such as the archaeal
chaperonin CpkB.
PMID- 28495563
TI - Resistance matters in EARNEST.
PMID- 28495564
TI - Characterization of Toll-like receptor 22 in turbot (Scophthalmus maximus).
AB - Toll-like receptors (TLRs) are essential for activation of the innate immune
system in response to invading pathogens. In this paper, expression profiles of
the turbot (Scophthalmus maximus) TLR22 gene (tbTLR22) were analyzed with RT-PCR
and in situ hybridization. Then its expression patterns simulated with ligands or
pathogens were investigated. Streptococcus iniae, Edwardsiella tarda, Hirame
rhabdovirus virus (HIRRV), polyinosinic: polycytidylic acid (Poly I:C),
peptidoglycan (PGN), or lipopolysaccharides (LPS) was injected to turbot; poly
I:C, PGN, or LPS was added into cultured peripheral blood leukocytes (PBL); and
then the tbTLR22 in liver, spleen, gill, kidney and cultured PBL was measured
using Quantitative PCR. The recombinant protein of tbTLR22 (rp-tbTLR22) and its
antibody were produced, then the reactions of antibody to tissues were detected
by Western-blotting, and the binding of rp-tbTLR22 to all the stimulants was
detected using ELISA. The results showed tbTLR22 expression was significantly up
regulated by PolyI: C, but no significant change in PGN and LPS groups; tbTLR22
significantly increased in liver and spleen after S. iniae infection with the
maximum of 3.6 times and 3.3 times; in liver and kidney after E. tarda infection
with the maximum of 3.4 times and 4.1 times; and then in gill and kidney after
HIRRV infection by 4.8 and 4.1 times. Rp-tbTLR22 antibody could recognize the
total protein from liver, kidney, gill and spleen at 40 kDa, 90 kDa and 120 kDa,
respectively. The rp-tbTLR22 could bind to three ligands and pathogens in vitro.
The expression and reaction data gave a clear recognization model of tbTLR22.
PMID- 28495565
TI - On the Post-Compaction Evolution of Tensile Strength of Sodium Chloride-Starch
Mixture Tablets.
AB - This study focuses on the evolution of mechanical behavior of starch and sodium
chloride (NaCl) mixture tablets after compaction. This type of mixture has
attracted attention in the past because such tablets exhibit lower tensile
strengths than the ones of its individual components. Here we demonstrate that
the strengths of NaCl-starch mixtures and NaCl tablets evolve after compaction in
an opposite way. When stored at relative humidity of 60%, NaCl tablets strengthen
with time, whereas NaCl-starch mixtures weaken. To explain this behavior, we
propose that in the NaCl-starch mixture, the presence of 2 materials with
significantly different elastic moduli leads to creation of tensile stresses at
the stiffer NaCl-NaCl contacts. Such tensile stresses lead to a reduction in
strength of the compacted mixtures by negating a local dissolution
reprecipitation mechanism, which strengthens the NaCl-NaCl in pure NaCl tablet.
This effect is proven by experimental results from NaCl specimens diametrically
loaded during storage.
PMID- 28495566
TI - The Constraints, Construction, and Verification of a Strain-Specific
Physiologically Based Pharmacokinetic Rat Model.
AB - The use of in vitro-in vivo extrapolation (IVIVE) techniques, mechanistically
incorporated within physiologically based pharmacokinetic (PBPK) models, can
harness in vitro drug data and enhance understanding of in vivo pharmacokinetics.
This study's objective was to develop a user-friendly rat (250 g, male Sprague
Dawley) IVIVE-linked PBPK model. A 13-compartment PBPK model including
mechanistic absorption models was developed, with required system data
(anatomical, physiological, and relevant IVIVE scaling factors) collated from
literature and analyzed. Overall, 178 system parameter values for the model are
provided. This study also highlights gaps in available system data required for
strain-specific rat PBPK model development. The model's functionality and
performance were assessed using previous literature-sourced in vitro properties
for diazepam, metoprolol, and midazolam. The results of simulations were compared
against observed pharmacokinetic rat data. Predicted and observed concentration
profiles in 10 tissues for diazepam after a single intravenous (i.v.) dose making
use of either observed i.v. clearance (CLiv) or in vitro hepatocyte intrinsic
clearance (CLint) for simulations generally led to good predictions in various
tissue compartments. Overall, all i.v. plasma concentration profiles were
successfully predicted. However, there were challenges in predicting oral plasma
concentration profiles for metoprolol and midazolam, and the potential reasons
and according solutions are discussed.
PMID- 28495567
TI - Transporters Involved in Metformin Pharmacokinetics and Treatment Response.
AB - Metformin, widely used as first-line treatment for type 2 diabetes, exists
primarily as a hydrophilic cation at physiological pHs. As such, membrane
transporters play a substantial role in its absorption, tissues distribution, and
renal elimination. Multiple organic cation transporters are determinants of the
pharmacokinetics of metformin, and many of them are important in its
pharmacological action, as mediators of metformin entry into target tissues.
Furthermore, a recent genome-wide association study in a large multi-ethnic
population implicated polymorphisms in SLC2A2, encoding the glucose transporter,
GLUT2, as important determinants of response to metformin. Here, we describe the
key transporters associated with metformin pharmacokinetics and response.
PMID- 28495568
TI - Quantitative Analyses of the Influence of Parameters Governing Rate-Determining
Process of Hepatic Elimination of Drugs on the Magnitudes of Drug-Drug
Interactions via Hepatic OATPs and CYP3A Using Physiologically Based
Pharmacokinetic Models.
AB - Physiologically based pharmacokinetic models were constructed for hepatic organic
anion-transporting polypeptides (OATPs) and cytochrome P450 3A (CYP3A) substrates
(bosentan, repaglinide, clarithromycin, and simeprevir), a CYP3A probe substrate
(midazolam), and selective inhibitors for OATPs (rifampicin) and CYP3A
(itraconazole), although the role of OATPs in the hepatic uptake of
clarithromycin is unclear. The pharmacokinetic data were obtained from our
previous clinical drug-drug interaction (DDI) study. Parameters optimized from
clinical PK data were confirmed to reproduce their blood concentrations in
control phase. DDIs with rifampicin and itraconazole were simulated using in vivo
Rdif (ratio of diffusional uptake to active uptake) and beta (the fraction of the
sum of intrinsic clearances for metabolism and biliary excretion in all possible
itineraries of intracellular drugs including basolateral efflux) estimated by
static analyses based on the extended clearance concept, in vivo inhibition
constant (Ki) for hepatic OATPs reported previously, and in vivo Ki for CYP3A
determined from DDI data with midazolam and itraconazole. Sensitivity analyses
showed the magnitudes of DDIs largely depended on Rdif and beta. In conclusion,
our approach using physiologically based pharmacokinetic modeling showed that the
rational estimation of parameters governing rate-determining process of hepatic
elimination is critical to accurately predict DDI magnitudes involving
OATPs/CYP3A inhibition.
PMID- 28495562
TI - Nucleoside reverse-transcriptase inhibitor cross-resistance and outcomes from
second-line antiretroviral therapy in the public health approach: an
observational analysis within the randomised, open-label, EARNEST trial.
AB - BACKGROUND: Cross-resistance after first-line antiretroviral therapy (ART)
failure is expected to impair activity of nucleoside reverse-transcriptase
inhibitors (NRTIs) in second-line therapy for patients with HIV, but evidence for
the effect of cross-resistance on virological outcomes is limited. We aimed to
assess the association between the activity, predicted by resistance testing, of
the NRTIs used in second-line therapy and treatment outcomes for patients
infected with HIV. METHODS: We did an observational analysis of additional data
from a published open-label, randomised trial of second-line ART (EARNEST) in sub
Saharan Africa. 1277 adults or adolescents infected with HIV in whom first-line
ART had failed (assessed by WHO criteria with virological confirmation) were
randomly assigned to a boosted protease inhibitor (standardised to ritonavir
boosted lopinavir) with two to three NRTIs (clinician-selected, without
resistance testing); or with raltegravir; or alone as protease inhibitor
monotherapy (discontinued after week 96). We tested genotypic resistance on
stored baseline samples in patients in the protease inhibitor and NRTI group and
calculated the predicted activity of prescribed second-line NRTIs. We measured
viral load in stored samples for all patients obtained every 12-16 weeks. This
trial is registered with Controlled-Trials.com (number ISRCTN 37737787) and
ClinicalTrials.gov (number NCT00988039). FINDINGS: Baseline genotypes were
available in 391 (92%) of 426 patients in the protease inhibitor and NRTI group.
176 (89%) of 198 patients prescribed a protease inhibitor with no predicted
active NRTIs had viral suppression (viral load <400 copies per mL) at week 144,
compared with 312 (81%) of 383 patients in the protease inhibitor and raltegravir
group at week 144 (p=0.02) and 233 (61%) of 280 patients in the protease
inhibitor monotherapy group at week 96 (p<0.0001). Compared with results with no
active NRTIs, 95 (85%) of 112 patients with one predicted-active NRTI had viral
suppression (p=0.3) and 20 (77%) of 26 patients with two or three active NRTIs
had viral suppression (p=0.08). Over all follow-up, greater predicted NRTI
activity was associated with worse viral load suppression (global p=0.0004).
INTERPRETATION: Genotypic resistance testing might not accurately predict NRTI
activity in protease inhibitor-based second-line ART. Our results do not support
the introduction of routine resistance testing in ART programmes in low-income
settings for the purpose of selecting second-line NRTIs. FUNDING: European and
Developing Countries Clinical Trials Partnership, UK Medical Research Council,
Institito de Salud Carlos III, Irish Aid, Swedish International Development
Cooperation Agency, Instituto Superiore di Sanita, WHO, Merck.
PMID- 28495569
TI - Plasma Lipidomics of Healthy Japanese Adults Reveals Gender- and Age-Related
Differences.
AB - Lipid metabolites in the blood are expected to be biomarker candidates to reflect
disease states and responses to therapeutic drugs. However, their profiles are
influenced by subject background, which may lead to confounding results. This
study aimed to evaluate whether age and gender affect lipid metabolite levels in
the plasma of healthy Japanese adults. Comprehensive lipidomic analysis was
performed using liquid chromatography-mass spectrometry for overnight fasted
volunteers consisting of 4 groups of 15 subjects each: young males (25-35 years),
elderly males (55-64 years), young females (25-35 years), and elderly females (55
65 years). Of 326 detected lipids, none showed significant gender-associated
differences in the young groups and 3 metabolites showed significant gender
associated differences in the elderly groups, suggesting that age has little
impact on plasma lipid levels in Japanese subjects. We found age-associated
differences in 111 (34%) and 115 (35%) metabolites in males and females,
respectively, indicating that the subjects' age should be considered an important
confounding factor for lipid biomarker exploration and validation studies in
Japanese populations. These findings provide fundamental information on biomarker
discovery, validation, and qualification processes in Japanese populations, and
facilitate the evaluation of biomarker candidates found in other populations.
PMID- 28495570
TI - Effect of chronic heart failure in older rats on respiratory muscle and hindlimb
blood flow during submaximal exercise.
AB - Submaximal exercise diaphragm blood flow (BF) is elevated in young chronic heart
failure (CHF) rats, while it is unknown if this occurs in older animals.
Respiratory and hindlimb muscle BFs (radiolabeled microspheres) were measured at
rest and during submaximal exercise (20m/min, 5% grade) in older healthy (n=7)
and CHF (n=6) Fischer 344X Brown Norway rats (27-29 mo old). Older CHF, compared
to healthy, rats had greater (p<0.01) left ventricular end-diastolic pressure and
right ventricle and lung weight (normalized to body weight). During submaximal
exercise, respiratory and hindlimb muscle BFs increased (p<0.02) in both groups,
while diaphragm BF was higher (CHF: 257+/-32; healthy: 121+/-9mL/min/100g,
p<0.01) and hindlimb BF lower (CHF: 111+/-10; healthy: 133+/-12mL/min/100g,
p=0.04) in older CHF compared to healthy rats. Submaximal exercise hindlimb BF
was negatively related (r=-0.93; p=0.03) to diaphragm BF in older CHF rats.
During submaximal exercise, diaphragm BF is elevated in older CHF compared to
healthy rats in proportion to the compromised hindlimb BF.
PMID- 28495571
TI - Role of iron in the pathogenesis of respiratory disease.
AB - Iron is essential for many biological processes, however, too much or too little
iron can result in a wide variety of pathological consequences, depending on the
organ system, tissue or cell type affected. In order to reduce pathogenesis, iron
levels are tightly controlled in throughout the body by regulatory systems that
control iron absorption, systemic transport and cellular uptake and storage.
Altered iron levels and/or dysregulated homeostasis have been associated with
several lung diseases, including chronic obstructive pulmonary disease, lung
cancer, cystic fibrosis, idiopathic pulmonary fibrosis and asthma. However, the
mechanisms that underpin these associations and whether iron plays a key role in
the pathogenesis of lung disease are yet to be fully elucidated. Furthermore, in
order to survive and replicate, pathogenic micro-organisms have evolved
strategies to source host iron, including freeing iron from cells and proteins
that store and transport iron. To counter these microbial strategies, mammals
have evolved immune-mediated defence mechanisms that reduce iron availability to
pathogens. This interplay between iron, infection and immunity has important
ramifications for the pathogenesis and management of human respiratory infections
and diseases. An increased understanding of the role that iron plays in the
pathogenesis of lung disease and respiratory infections may help inform novel
therapeutic strategies. Here we review the clinical and experimental evidence
that highlights the potential importance of iron in respiratory diseases and
infections.
PMID- 28495572
TI - A Tumor Ultrasound-guided Incision (TUGI) Approach to Nipple-sparing Mastectomy:
Balancing Oncologic Safety and Technical Outcomes.
AB - BACKGROUND: Nipple-sparing mastectomy (NSM) is a prevalent operation for patients
with breast cancer. Indications have been limited to tumors accessible via
radial, infra-mammary, or periareolar incisions out of concern for oncologic and
technical safety. We study an alternative approach to NSM based on tumor
ultrasound-guided incisions (TUGI) and report its oncologic and technical
outcomes. MATERIALS AND METHODS: A retrospective chart review examined patients
who underwent TUGI NSM between 2013 and 2016. Operative notes, postoperative
notes, pathology reports, and postoperative photography were analyzed. RESULTS:
Ninety-four patients had mastectomy with reconstruction performed over a 3-year
period by the senior authors. Of those, 31 (33%) were NSM and 13 (14%) had the
TUGI technique, forming the study group. The median tumor size was 1.5 cm, with a
median distance from the nipple areolar complex of 5 cm. Sixty-two percent of the
incisions were in the upper quadrants of the breast. Median operative time was
207 minutes. Zero patients had positive margins. One hundred percent of patients
underwent immediate tissue expander placement, 46% with acellular dermal matrix.
For final reconstruction, 23% had a free flap, 69% implant, and 8% are still
pending. Eight percent of patients had wound infection, and 15% of patients had
NAC necrosis. No cancer recurrence has been observed at a median follow-up of 17
months. CONCLUSION: TUGI offers a valuable, oncologically sound alternative
approach to traditional NSM. The technical results and outcomes support its use
in selected patients with breast cancer undergoing NSM.
PMID- 28495573
TI - Spatial mapping of humeral head bone density.
AB - BACKGROUND: Short-stem humeral replacements achieve fixation by anchoring to the
metaphyseal trabecular bone. Fixing the implant in high-density bone can provide
strong fixation and reduce the risk of loosening. However, there is a lack of
data mapping the bone density distribution in the proximal humerus. The aim of
the study was to investigate the bone density in proximal humerus. METHODS: Eight
computed tomography scans of healthy cadaveric humeri were used to map bone
density distribution in the humeral head. The proximal humeral head was divided
into 12 slices parallel to the humeral anatomic neck. Each slice was then divided
into 4 concentric circles. The slices below the anatomic neck, where short-stem
implants have their fixation features, were further divided into radial sectors.
The average bone density for each of these regions was calculated, and regions of
interest were compared using a repeated-measures analysis of variance with
significance set at P < .05. RESULTS: Average apparent bone density was found to
decrease from proximal to distal regions, with the majority of higher bone
density proximal to the anatomic neck of the humerus (P < .05). Below the
anatomic neck, bone density increases from central to peripheral regions, where
cortical bone eventually occupies the space (P < .05). In distal slices below the
anatomic neck, a higher bone density distribution in the medial calcar region was
also observed. CONCLUSION: This study indicates that it is advantageous with
respect to implant fixation to preserve some bone above the anatomic neck and
epiphyseal plate and to use the denser bone at the periphery.
PMID- 28495574
TI - Does acromioplasty result in favorable clinical and radiologic outcomes in the
management of chronic subacromial pain syndrome? A double-blinded randomized
clinical trial with 9 to 14 years' follow-up.
AB - BACKGROUND: The treatment effect of acromioplasty for chronic subacromial pain
syndrome (SAPS) on long-term shoulder function and rotator cuff deterioration has
still to be determined. This study aimed to determine the long-term clinical and
radiologic treatment effect of arthroscopic acromioplasty in patients with
chronic SAPS. METHODS: In this double-blind, randomized clinical trial, 56
patients with chronic SAPS (median age, 47 years; age range, 31-60 years) were
randomly allocated to arthroscopic bursectomy alone or to bursectomy combined
with acromioplasty and were followed up for a median of 12 years. The primary
outcome was the Constant score. Secondary outcomes included the Simple Shoulder
Test, visual analog scale (VAS) for pain, VAS for shoulder functionality, and
rotator cuff integrity assessed with magnetic resonance imaging or ultrasound.
RESULTS: A total of 43 patients (77%) were examined at a median of 12 years'
follow-up. Intention-to-treat analysis at 12 years' follow-up did not show a
significant additional treatment effect of acromioplasty on bursectomy alone in
improvement in Constant score (5 points; 95% confidence interval, -5.1 to 15.6),
Simple Shoulder Test score, VAS score for pain, or VAS score for shoulder
function. The prevalence of rotator cuff tears was not significantly different
between the bursectomy group (17%) and acromioplasty group (10%). CONCLUSIONS:
There were no relevant additional effects of arthroscopic acromioplasty on
bursectomy alone with respect to clinical outcomes and rotator cuff integrity at
12 years' follow-up. These findings bring the effectiveness of acromioplasty into
question and may support the idea of a more conservative approach in the initial
treatment of SAPS.
PMID- 28495575
TI - The relationship between the incidence of adhesive capsulitis and hemoglobin A1c.
AB - BACKGROUND: Previous studies have shown no correlation between adhesive
capsulitis and hemoglobin A1c (HbA1c). However, HbA1c is only a measure of short
term blood sugar control. We created a previously nonvalidated variable,
cumulative HbA1c, that uses HbA1c values over time to estimate the total disease
burden a single individual experiences over a period. In this study, we aimed to
evaluate whether a correlation exists between cumulative HbA1c levels in diabetic
patients and the prevalence of frozen shoulder. We hypothesized that poor long
term glucose control would be correlated with increased incidence of adhesive
capsulitis. METHODS: A retrospective analysis at a single institution was
performed. Data from all patients from a single institution with any HbA1c values
were collected. A total of 24,417 patients met the inclusion criteria. A variable
was created establishing the cumulative magnitude of abnormal HbA1c values over
time, termed "cumulative HbA1c." Logistic regression analysis was performed to
determine whether long-term glucose control was predictive of the development of
adhesive capsulitis. RESULTS: Cumulative HbA1c was positively associated with
adhesive capsulitis (7.6 * 10-5) (ie, odds ratio of 1.000076). The effect size of
cumulative HbA1c on adhesive capsulitis was significant; for each unit of time
that the HbA1c level was greater than 7, there was a 2.77% increase in the risk
of adhesive capsulitis. DISCUSSION: Cumulative HbA1c was associated with an
increased incidence of adhesive capsulitis. This finding suggests that the
effects of diabetes that predispose patients to the development of adhesive
capsulitis are dose dependent. Patients with worse blood sugar control over a
longer period are at an increased risk of the development of adhesive capsulitis.
PMID- 28495576
TI - Quantitative assessment of fatty infiltration and muscle volume of the rotator
cuff muscles using 3-dimensional 2-point Dixon magnetic resonance imaging.
AB - BACKGROUND: In patients with rotator cuff tears, muscle degeneration is known to
be a predictor of irreparable tears and poor outcomes after surgical repair.
Fatty infiltration and volume of the whole muscles constituting the rotator cuff
were quantitatively assessed using 3-dimensional 2-point Dixon magnetic resonance
imaging. METHODS: Ten shoulders with a partial-thickness tear, 10 shoulders with
an isolated supraspinatus tear, and 10 shoulders with a massive tear involving
supraspinatus and infraspinatus were compared with 10 control shoulders after
matching age and sex. With segmentation of muscle boundaries, the fat fraction
value and the volume of the whole rotator cuff muscles were computed. After
reliabilities were determined, differences in fat fraction, muscle volume, and
fat-free muscle volume were evaluated. RESULTS: Intra-rater and inter-rater
reliabilities were regarded as excellent for fat fraction and muscle volume.
Tendon rupture adversely increased the fat fraction value of the respective
rotator cuff muscle (P < .002). In the massive tear group, muscle volume was
significantly decreased in the infraspinatus (P = .035) and increased in the
teres minor (P = .039). With subtraction of fat volume, a significant decrease of
fat-free volume of the supraspinatus muscle became apparent with a massive tear
(P = .003). CONCLUSION: Three-dimensional measurement could evaluate fatty
infiltration and muscular volume with excellent reliabilities. The present study
showed that chronic rupture of the tendon adversely increases the fat fraction of
the respective muscle and indicates that the residual capacity of the rotator
cuff muscles might be overestimated in patients with severe fatty infiltration.
PMID- 28495578
TI - Expression pattern and functional analysis of fundc1 in rare minnow (Gobiocypris
rarus).
AB - Fundc1 is a mitochondrial outer membrane protein and plays important roles in
mitochondria fission and hypoxia-induced mitophagy in mammalian cells. However,
there is no relevant report of fundc1 in fish. In the present study, we cloned a
942bp fundc1 cDNA from rare minnow. The cDNA, designated as Grfundc1 cDNA,
contains an open reading frame (ORF) of 459bp which encodes a polypeptide of 152
amino acid residues. Comparisons of deduced amino acid sequences demonstrated
that Grfundc1 was highly homologous with those of other vertebrates. RT-PCR and
real time PCR detection revealed that the transcripts of Grfundc1 were not
detectable in the unfertilized eggs and had high levels at blastula and gastrula
stages. Whole mount in situ hybridization analysis observed that Grfundc1 was
ubiquitously expressed at early stage and later riched in specific regions, such
as brain, branchial arch, eye and somite during embryogenesis. Grfundc1 was
expressed in all the tissues of rare minnow adult, including brain, liver, gill,
eyes, heart, kidney, intestine, muscle, testis and ovary. The expression of
Grfundc1 in the brain, gill, heart and eye of rare minnow adult was significantly
down-regulated by hypoxia. Similar hypoxic response was observed in the rare
minnow embryos at 48hpf following hypoxia exposure. Functional analysis showed
that knockdown of Grfundc1 significantly caused defects in the body axis and
dorsal neural tissues of rare minnow embryos. These results indicate that
Grfundc1 may play important roles in embryogenesis in fish.
PMID- 28495577
TI - Delivery of anti-inflammatory peptides from hollow PEGylated poly(NIPAM)
nanoparticles reduces inflammation in an ex vivo osteoarthritis model.
AB - Targeted delivery of anti-inflammatory osteoarthritis treatments have the
potential to significantly decrease undesirable systemic side effects and reduce
required therapeutic dosage. Here we present a targeted, non-invasive drug
delivery system to decrease inflammation in an osteoarthritis model. Hollow
thermoresponsive poly(N-isopropylacrylamide) (pNIPAM) nanoparticles have been
synthesized via degradation of a N,N'-bis(acryloyl)cystamine (BAC) cross-linked
core out of a non-degradable pNIPAM shell. Sulfated 2-acrylamido-2-methyl-1
propanesulfonic acid (AMPSA) was copolymerized in the shell to increase passive
loading of an anti-inflammatory mitogen-activated protein kinase-activated
protein kinase 2 (MK2)-inhibiting cell-penetrating peptide (KAFAK). The drug
loaded hollow nanoparticles were effective at delivering a therapeutically active
dose of KAFAK to bovine cartilage explants, suppressing pro-inflammatory
interleukin-6 (IL-6) expression after interleukin-1 beta (IL-1beta) stimulation.
This thermosensitive hollow nanoparticle system provides an excellent platform
for the delivery of peptide therapeutics into highly proteolytic environments
such as osteoarthritis.
PMID- 28495579
TI - A new chemotherapy agent-free theranostic system composed of graphene oxide nano
complex and aptamers for treatment of cancer cells.
AB - The common cancer treatment strategies like chemotherapy and radiotherapy are
nonspecific and can trigger severe side effects by damaging normal cells. So,
targeted cancer therapies, such as apoptosis induction, have attracted great
attention in recent years. In this project, two nano-complexes, MUC1 aptamer-NAS
24 aptamer-Graphene oxide (GO) and MUC1 aptamer-Cytochrome C aptamer-GO, were
designed to induce cell programmed death in MDA-MB-231 and MCF-7 cells (breast
cancer cell lines) and to verify the level of apoptosis in both cell lines. MUC1
aptamer was a molecular recognition probe that led the internalization of two
nano-complexes into MDA-MB-231 and MCF-7 cells (MUC1 positive cells) but not into
HepG2 cell (liver cancer cell line, MUC1 negative cells). The apoptosis induction
relied on binding of NAS-24 aptamer to its target, vimentin, in MDA-MB-231 and
MCF-7 (target cells) with different levels of vimentin content. The function of
first nano-complex was confirmed by binding of FAM-labeled cytochrome C aptamer
to its target (cytochrome C) which was released from mitochondria, based on the
function of the first nano-complex. Fluorometric analysis and gel retardation
assay proved the formation of nano-complexes. The results of flow cytometry and
fluorescence microscopy indicated efficient apoptosis induction just in target
cells (MDA-MB-231 and MCF-7 cells) but not in non-target cells (HepG2 cell). The
results of MTT assay also confirmed cell death process. Overall, our results
proved excellent targeted apoptosis in breast cancer cells by designed nano
complexes which can be applied as an efficient cancer therapy method.
PMID- 28495580
TI - Novel Curcumin loaded nanoparticles engineered for Blood-Brain Barrier crossing
and able to disrupt Abeta aggregates.
AB - The formation of extracellular aggregates built up by deposits of beta-amyloid
(Abeta) is a hallmark of Alzheimer's disease (AD). Curcumin has been reported to
display anti-amyloidogenic activity, not only by inhibiting the formation of new
Abeta aggregates, but also by disaggregating existing ones. However, the uptake
of Curcumin into the brain is severely restricted by its low ability to cross the
blood-brain barrier (BBB). Therefore, novel strategies for a targeted delivery of
Curcumin into the brain are highly desired. Here, we encapsulated Curcumin as
active ingredient in PLGA (polylactide-co-glycolic-acid) nanoparticles (NPs),
modified with g7 ligand for BBB crossing. We performed in depth analyses of
possible toxicity of these NPs, uptake, and, foremost, their ability to influence
Abeta pathology in vitro using primary hippocampal cell cultures. Our results
show no apparent toxicity of the formulated NPs, but a significant decrease of
Abeta aggregates in response to Curcumin loaded NPs. We thus conclude that brain
delivery of Curcumin using BBB crossing NPs is a promising future approach in the
treatment of AD.
PMID- 28495581
TI - Dipicolinic acid as a novel spore-inspired excipient for antibody formulation.
AB - Ionic excipients are commonly used in aqueous therapeutic monoclonal antibody
(mAb) formulations. Novel excipients are of industrial interest, with a recent
focus on Arg salt forms and their application as viscosity reducing and
stabilizing additives. Here, we report that the calcium salt of dipicolinic acid
(DPA, pyridine-2,6-dicarboxylic acid), uniquely present in nature in the core of
certain bacterial spores, reduces the viscosity of a mAb formulated at 150mg/mL,
below that achieved by Arg hydrochloride at the same concentration (10mM). DPA
also reduced the reversible phase separation of the same formulation, which
characteristically occurs for this mAb upon cooling to 4 degrees C. Differential
scanning calorimetry and differential scanning fluorimetry did not reveal a
conformation destabilisation of the mAb in the presence of 10mM DPA, or by the
related quinolinic acid (QA, pyridine-2,3-dicarboxylic acid). However,
fluorescence spectrophotometry did reveal localised (aromatic) conformational
changes to the mAb attributed to DPA, dependent on the salt form. While precise
mechanisms of action remain to be identified, our preliminary data suggest that
these DPA salts are worthy of further investigation as novel ionic excipient for
biologics formulation.
PMID- 28495582
TI - Evaluation of lipid-stabilised tripropionin nanodroplets as a delivery route for
combretastatin A4.
AB - Lipid-based nanoemulsions are a cheap and elegant route for improving the
delivery of hydrophobic drugs. Easy and quick to prepare, nanoemulsions have
promise for the delivery of different therapeutic agents. Although multiple
studies have investigated the effects of the oil and preparation conditions on
the size of the nanoemulsion nanodroplets for food applications, analogous
studies for nanoemulsions for therapeutic applications are limited. Here we
present a study on the production of lipid-stabilised oil nanodroplets (LONDs)
towards medical applications. A number of biocompatible oils were used to form
LONDs with phospholipid coatings, and among these, squalane and tripropionin were
chosen as model oils for subsequent studies. LONDs were formed by high pressure
homogenisation, and their size was found to decrease with increasing production
pressure. When produced at 175MPa, all LONDs samples exhibited sizes between 100
and 300nm, with polydispersity index PI between 0.1 and 0.3. The LONDs were
stable for over six weeks, at 4 degrees C, and also under physiological
conditions, showing modest changes in size (<10%). The hydrophobic drug
combretastatin A4 (CA4) was encapsulated in tripropionin LONDs with an efficiency
of approximately 76%, achieving drug concentration of approximately 1.3mg/ml. SVR
mouse endothelial cells treated with CA4 tripropionin LONDs showed the
microtubule disruption, characteristic of drug uptake for all tested doses, which
suggests successful release of the CA4 from the LONDs.
PMID- 28495583
TI - Application of miscibility analysis and determination of Soluplus solubility map
for development of carvedilol-loaded nanofibers.
AB - Electrospinning was used to produce carvedilol-loaded Soluplus polymer nanofibers
using a systematic approach. Miscibility between drug and polymer was determined
through calculation of the interaction parameter, chi, and the difference between
the total solubility parameters, Deltadt. A solubility map for Soluplus was
obtained by examining different solvent systems, carrying out electrospinning,
and characterizing the nanofibers formed. Miscibility studies showed that
carvedilol and Soluplus can form a miscible system (chi=-2.3054;
Deltadeltat<7.0MPa1/2). Based on the Soluplus solubility map, acetone: chloroform
(90:10; w/w) represents a suitable solvent system for electrospinning of
carvedilol-loaded Soluplus nanofibers. Scanning electron microscopy of these
nanofiber samples showed smooth surface morphology. The nanofibers had a regular
cylindrical morphology. Beads appeared along the nanofibers more frequently in
formulations with lower percentages of carvedilol. Differential scanning
calorimetry showed no melting endothermic peak for carvedilol, which suggests its
complete conversion from the crystalline to the amorphous form (at polymer:
carvedilol 1:1). The infrared spectrum of the carvedilol-loaded Soluplus
nanofibers showed no characteristic carvedilol peak at 3344.5cm-1, which suggests
interactions between carvedilol and Soluplus. Dissolution studies of these
nanofibers showed improved pure carvedilol dissolution properties, with >85% of
the carvedilol released in the first 15min, versus 20% for pure carvedilol. The
use of miscibility analysis and polymer solubility studies demonstrate great
technological potential to tackle the challenge for inadequate dissolution of
poorly water-soluble drugs.
PMID- 28495584
TI - Food effects in paediatric medicines development for products Co-administered
with food.
AB - A small amount of food is commonly used to aid administration of medicines to
children to improve palatability and/or swallowability. However the impact of
this co-administered food on the absorption and subsequent pharmacokinetic
profile of the drug is unknown. Existing information on food effects is limited
to standard protocols used to evaluate the impact of a high fat meal in an adult
population using the adult medication. In the absence of a substantial body of
data, there are no specific guidelines available during development of paediatric
products relating to low volumes of potentially low calorie food. This paper
brings together expertise to consider how the impact of co-administered food can
be risk assessed during the development of a paediatric medicine. Two case
studies were used to facilitate discussions and seek out commonalities in risk
assessing paediatric products; these case studies used model drugs that differed
in their solubility, a poorly soluble drug that demonstrated a positive food
effect in adults and a highly soluble drug where a negative food effect was
observed. For poorly soluble drugs risk assessments are centred upon
understanding the impact of food on the in vivo solubility of the drug which
requires knowledge of the composition of the food and the volumes present within
the paediatric gastrointestinal tract. Further work is required to develop age
appropriate in vitro and in silico models that are representative of paediatric
populations. For soluble drugs it is more important to understand the mechanisms
that may lead to a food effect, this may include interactions with transporters
or the impact of the food composition on gastro-intestinal transit or even
altered gastric motility. In silico models have the most promise for highly
soluble drug products although it is essential that these models reflect the
relevant mechanisms involved in potential food effects. The development of
appropriate in vitro and in silico tools is limited by the lack of available
clinical data that is critical to validate any tool. Further work is required to
identify globally acceptable and available vehicles that should be the first
option for co-administration with medicines to enable rapid and relevant risk
assessment.
PMID- 28495585
TI - Rapid separation of very low concentrations of bacteria from blood.
AB - A rapid and accurate diagnosis of the species and antibiotic resistance of
bacteria in septic blood is vital to increase survival rates of patients with
bloodstream infections, particularly those with carbapenem-resistant
enterobacteriaceae (CRE) infections. The extremely low levels in blood (1 to
100CFU/ml) make rapid diagnosis difficult. In this study, very low concentrations
of bacteria (6 to 200CFU/ml) were separated from 7ml of whole blood using rapid
sedimentation in a spinning hollow disk that separated plasma from red and white
cells, leaving most of the bacteria suspended in the plasma. Following less than
a minute of spinning, the disk was slowed, the plasma was recovered, and the
bacteria were isolated by vacuum filtration. The filters were grown on nutrient
plates to determine the number of bacteria recovered from the blood. Experiments
were done without red blood cell (RBC) lysis and with RBC lysis in the recovered
plasma. While there was scatter in the data from blood with low bacterial
concentrations, the mean average recovery was 69%. The gender of the blood donor
made no statistical difference in bacterial recovery. These results show that
this rapid technique recovers a significant amount of bacteria from blood
containing clinically relevant low levels of bacteria, producing the bacteria in
minutes. These bacteria could subsequently be identified by molecular techniques
to quickly identify the infectious organism and its resistance profile, thus
greatly reducing the time needed to correctly diagnose and treat a blood
infection.
PMID- 28495586
TI - Solid-phase synthesis of highly repetitive chromatin assembly templates.
AB - DNA templates for assembling chromatin model systems typically consist of
numerous repeats of nucleosome positioning sequences, making their synthesis
challenging. Here we describe a solid-phase strategy for generating such
templates using sequential enzymatic ligation of DNA monomers. Using single
nucleosome site monomers, we can either generate a twelve-nucleosome site target,
or systematically access intermediate-sized templates. Using twelve nucleosome
positioning site monomers, longer templates can be generated. Our synthesized
templates assemble into well-defined chromatin model systems, demonstrating the
utility of our solid-phase approach. Moreover, our strategy should be more widely
applicable to generating other DNAs containing highly repetitive DNA sequences.
PMID- 28495587
TI - Dose-response analysis of epigenetic, metabolic, and apical endpoints after short
term exposure to experimental hepatotoxicants.
AB - Identification of sensitive and novel biomarkers or endpoints associated with
toxicity and carcinogenesis is of a high priority. There is increasing interest
in the incorporation of epigenetic and metabolic biomarkers to complement apical
data; however, a number of questions, including the tissue specificity, dose
response patterns, early detection of those endpoints, and the added value need
to be addressed. In this study, we investigated the dose-response relationship
between apical, epigenetic, and metabolomics endpoints following short-term
exposure to experimental hepatotoxicants, clofibrate (CF) and phenobarbital (PB).
Male F344 rats were exposed to PB (0, 5, 25, and 100 mg/kg/day) or CF (0, 10, 50,
and 250 mg/kg/day) for seven days. Exposure to PB or CF resulted in dose
dependent increases in relative liver weights, hepatocellular hypertrophy and
proliferation, and increases in Cyp2b1 and Cyp4a1 transcripts. These changes were
associated with altered histone modifications within the regulatory units of
cytochrome genes, LINE-1 DNA hypomethylation, and altered microRNA profiles.
Metabolomics data indicated alterations in the metabolism of bile acids. This
study provides the first comprehensive analysis of the apical, epigenetic and
metabolic alterations, and suggests that the latter two occur within or near the
dose response curve of apical endpoint alterations following exposure to
experimental hepatotoxicants.
PMID- 28495588
TI - RIFM fragrance ingredient safety assessment, Isoamyl butyrate, CAS Registry
Number 106-27-4.
PMID- 28495591
TI - The HLA-DR mediated signalling increases the migration and invasion of melanoma
cells, the expression and lipid raft recruitment of adhesion receptors, PD-L1 and
signal transduction proteins.
AB - The constitutive expression of Major Histocompatibility Complex (MHC) class II
molecules is restricted to professional Antigen-Presenting Cells (APCs),
nevertheless almost 50% of melanomas express constitutively the MHC class II
molecules. Therefore, in two MHC class II constitutive expressing melanoma cell
lines we studied the signalling mediated by the HLA-DR molecules in the aim to
understand the consequence of class II mediated signalling on metastatic
dissemination of melanoma. In particular, we reported that the HLA-DR mediated
signalling play a new role in melanoma progression, increasing the migration and
invasion of melanoma cells. Furthermore, we showed that the HLA-DR mediated
signalling increases the expression and the lipid raft localisation of class II
molecules, PD-L1 receptor, Integrin and CAM adhesion receptors, FAK, AKT and
STAT3 signalling proteins. We also showed that the HLA-DR mediated signalling
increases the activation of FAK, AKT, ERK, PKC and STAT3 signalling proteins and
the expression of ILK, PAX, BRAF, ERK and PKC. Indeed, the results showed suggest
that the HLA-DR mediated signalling provides a platform useful to frustrate an
effective anti-tumour response and to increase melanoma migration and metastatic
dissemination of this cancer.
PMID- 28495590
TI - Concurrent activation of beta2-adrenergic receptor and blockage of GPR55 disrupts
pro-oncogenic signaling in glioma cells.
AB - Activation of beta2-adrenergic receptor (beta2AR) and deorphanized GPR55 has been
shown to modulate cancer growth in diverse tumor types in vitro and in xenograft
models in vivo. (R,R')-4'-methoxy-1-naphthylfenoterol [(R,R')-MNF] is a bivalent
compound that agonizes beta2AR but inhibits GPR55-mediated pro-oncogenic
responses. Here, we investigated the molecular mechanisms underlying the anti
tumorigenic effects of concurrent beta2AR activation and GPR55 blockade in C6
glioma cells using (R,R')-MNF as a marker ligand. Our data show that (R,R')-MNF
elicited G1-phase cell cycle arrest and apoptosis, reduced serum-inducible cell
motility, promoted the phosphorylation of PKA target proteins, and inhibited
constitutive activation of ERK and AKT in the low nanomolar range, whereas high
nanomolar levels of (R,R')-MNF were required to block GPR55-mediated cell
motility. siRNA knockdown and pharmacological inhibition of beta2AR activity were
accompanied by significant upregulation of AKT and ERK phosphorylation, and
selective alteration in (R,R')-MNF responsiveness. The effects of agonist
stimulation of GPR55 on various readouts, including cell motility assays, were
suppressed by (R,R')-MNF. Lastly, a significant increase in phosphorylation
mediated inactivation of beta-catenin occurred with (R,R')-MNF, and we provided
new evidence of (R,R')-MNF-mediated inhibition of oncogenic beta-catenin
signaling in a C6 xenograft tumor model. Thus, simultaneous activation of beta2AR
and blockade of GPR55 may represent a novel therapeutic approach to combat the
progression of glioblastoma cancer.
PMID- 28495589
TI - Reduced FAK-STAT3 signaling contributes to ER stress-induced mitochondrial
dysfunction and death in endothelial cells.
AB - Excessive endoplasmic reticulum (ER) stress leads to cell loss in many diseases,
e.g., contributing to endothelial cell loss after spinal cord injury. Here, we
determined whether ER stress-induced mitochondrial dysfunction could be explained
by interruption of the focal adhesion kinase (FAK)-mitochondrial STAT3 pathway we
recently discovered. ER stress was induced in brain-derived mouse bEnd5
endothelial cells by thapsigargin or tunicamycin and caused apoptotic cell death
over a 72h period. In concert, ER stress caused mitochondrial dysfunction as
shown by reduced bioenergetic function, loss of mitochondrial membrane potential
and increased mitophagy. ER stress caused a reduction in mitochondrial
phosphorylated S727-STAT3, known to be important for maintaining mitochondrial
function. Normal activation or phosphorylation of the upstream cytoplasmic FAK
was also reduced, through mechanisms that involve tyrosine phosphatases and
calcium signaling, as shown by pharmacological inhibitors, bisperoxovanadium
(bpV) and 2-aminoethoxydiphenylborane (APB), respectively. APB mitigated the
reduction in FAK and STAT3 phosphorylation, and improved endothelial cell
survival caused by ER stress. Transfection of cells rendered null for STAT3 using
CRISPR technology with STAT3 mutants confirmed the specific involvement of S727
STAT3 inhibition in ER stress-mediated cell loss. These data suggest that loss of
FAK signaling during ER stress causes mitochondrial dysfunction by reducing the
protective effects of mitochondrial STAT3, leading to endothelial cell death. We
propose that stimulation of the FAK-STAT3 pathway is a novel therapeutic approach
against pathological ER stress.
PMID- 28495592
TI - miR-21 Promotes Fibrogenesis in Peritoneal Dialysis.
AB - Peritoneal dialysis (PD) is a life-saving form of renal replacement therapy for
those with end-stage kidney disease. Mesothelial cells (MCs) line the peritoneal
cavity and help define peritoneal response to treatment-associated injury, a
major reason for treatment failure. miRNAs are important regulators, but their
roles in peritoneal fibrosis are largely unknown. In this study, miR-21 was one
of the most abundant miRNAs in primary MCs, and was up-regulated by the
profibrotic cytokine transforming growth factor-beta1 and in PD effluent-derived
MCs exhibiting mesenchymal phenotypic change. Increased miR-21 was found in
peritoneal membrane biopsy specimens from PD patients compared to healthy
controls (PD biocompatible, 5.86*, P = 0.0001; PD conventional, 7.09*, P <
0.0001, n = 11 per group). In PD effluent from a cohort of 230 patients, miR-21
was higher in those receiving the therapy long-term compared to new starters (n =
230, miR-21 3.26*, P = 0.001) and associated with icodextrin use (R = 0.52; 95%
CI, 0.20-0.84), peritonitis count (R = 0.16; 95% CI, 0.03-0.29), and dialysate
cytokines. miR-21 down-regulated programmed cell death 4 and programmed cell
death 4 protein was decreased in peritoneal membrane biopsy specimens from PD
patients compared to healthy controls. New miR-21 targets were identified that
may be important during PD fibrogenesis. These data identify miR-21 as an
important effector of fibrosis in the peritoneal membrane, and a promising
biomarker in the dialysis effluent for membrane change in patients receiving PD.
PMID- 28495593
TI - Enhanced air dispersion modelling at a typical Chinese nuclear power plant site:
Coupling RIMPUFF with two advanced diagnostic wind models.
AB - An enhanced air dispersion modelling scheme is proposed to cope with the building
layout and complex terrain of a typical Chinese nuclear power plant (NPP) site.
In this modelling, the California Meteorological Model (CALMET) and the
Stationary Wind Fit and Turbulence (SWIFT) are coupled with the Riso Mesoscale
PUFF model (RIMPUFF) for refined wind field calculation. The near-field diffusion
coefficient correction scheme of the Atmospheric Relative Concentrations in the
Building Wakes Computer Code (ARCON96) is adopted to characterize dispersion in
building arrays. The proposed method is evaluated by a wind tunnel experiment
that replicates the typical Chinese NPP site. For both wind speed/direction and
air concentration, the enhanced modelling predictions agree well with the
observations. The fraction of the predictions within a factor of 2 and 5 of
observations exceeds 55% and 82% respectively in the building area and the
complex terrain area. This demonstrates the feasibility of the new enhanced
modelling for typical Chinese NPP sites.
PMID- 28495595
TI - Low plasma leptin level at admission predicts delirium in critically ill
patients: A prospective cohort study.
AB - The pathophysiology of delirium remains poorly understood. Low leptin level has
been associated with features leading to delirium such as dysregulated immune
functions and loss of neuroprotective effects. The purpose of the present study
was to investigate the relationship between plasma leptin level at intensive care
unit (ICU) entry and subsequent occurrence of delirium in critically ill
patients. This single-center prospective cohort study in China allocated 336
critically ill patients admitted to ICU between 05/2015 and 05/2016 into a
delirium group (n=102) and non-delirium group (n=234) based on whether delirium
occurred during their stay at the ICU. Patients were examined at least twice
daily and delirium was diagnosed using the Confusion Assessment Method for the
ICU (CAM-ICU). Blood samples were obtained after ICU entry. Plasma leptin
concentrations were measured by ELISA. Delirium occurred in 30.4% (102/336) of
patients. Patients who developed delirium showed significantly lower leptin level
at ICU entry than those who did not (6.1+/-3.2 vs. 9.2+/-5.9ng/mL; P<0.001). Low
plasma leptin level at ICU entry was independently associated with subsequent
occurrence of delirium (OR, 0.865; 95%CI, 0.802-0.934; P<0.001). Other
independent risk factors for delirium included increasing age (OR, 1.050; 95%CI,
1.020-1.080; P=0.001) and Acute Physiology and Chronic Health Evaluation-II
(APACHE-II) score (OR, 1.148; 95%CI, 1.092-1.208; P<0.001). Patients who
developed delirium had a prolonged duration of ICU stay and higher mortality. Low
plasma leptin level at ICU entry was associated with the occurrence of delirium
in critically ill patients.
PMID- 28495594
TI - Elevated MUs-ms timescale backbone dynamics in the transition state analog form
of arginine kinase.
AB - Arginine kinase catalyzes reversible phosphoryl transfer between arginine and
ATP. Crystal structures of arginine kinase in an open, substrate-free form and
closed, transition state analog (TSA) complex indicate that the enzyme undergoes
substantial domain and loop rearrangements required for substrate binding,
catalysis, and product release. Nuclear magnetic resonance (NMR) has shown that
substrate-free arginine kinase is rigid on the ps-ns timescale (average S2=0.84+/
0.08) yet quite dynamic on the us-ms timescale (35 residues with Rex, 12%), and
that movements of the N-terminal domain and the loop comprising residues I182
G209 are rate-limiting on catalysis. Here, NMR of the TSA-bound enzyme shows
similar rigidity on the ps-ns timescale (average S2=0.91+/-0.05) and
substantially increased MUs-ms timescale dynamics (77 residues; 22%). Many of the
residues displaying MUs-ms dynamics in NMR Carr-Purcell-Meiboom-Gill (CPMG) 15N
backbone relaxation dispersion experiments of the TSA complex are also dynamic in
substrate-free enzyme. However, the presence of additional dynamic residues in
the TSA-bound form suggests that dynamics extend through much of the C-terminal
domain, which indicates that in the closed form, a larger fraction of the protein
takes part in conformational transitions to the excited state(s). Conformational
exchange rate constants (kex) of the TSA complex are all approximately 2500s-1,
higher than any observed in the substrate-free enzyme (800-1900s-1). Elevated MUs
ms timescale protein dynamics in the TSA-bound enzyme is more consistent with
recently postulated catalytic networks involving multiple interconnected states
at each step of the reaction, rather than a classical single stabilized
transition state.
PMID- 28495596
TI - The role of Omega-3 and Omega-9 fatty acids for the treatment of neuropathic pain
after neurotrauma.
AB - Omega-3 polyunsaturated fatty acids (PUFAs), such as docosaexaenoic acid (DHA)
and eicosapentaenoic acid (EPA), mediate neuroactive effects in experimental
models of traumatic peripheral nerve and spinal cord injury. Cellular mechanisms
of PUFAs include reduced neuroinflammation and oxidative stress, enhanced
neurotrophic support, and activation of cell survival pathways. Bioactive Omega-9
monounsaturated fatty acids, such as oleic acid (OA) and 2-hydroxy oleic acid (2
OHOA), also show therapeutic effects in neurotrauma models. These FAs reduces
noxious hyperreflexia and pain-related anxiety behavior following peripheral
nerve injury and improves sensorimotor function following spinal cord injury
(SCI), including facilitation of descending inhibitory antinociception. The
relative safe profile of neuroactive fatty acids (FAs) holds promise for the
future clinical development of these molecules as analgesic agents. This article
is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting
Biomembranes edited by Pablo V. Escriba.
PMID- 28495597
TI - The learned reinterpretation of fluency in amnesia.
AB - Fluency is one of many cues that are involved in memory decisions. To date,
however, the extent to which fluency-based decisions are preserved in amnesia is
not yet clear. In this study, we tested and found differences in how patients
with amnesia (n=8) and control participants (n=16) use fluency when making
recognition decisions (Experiment 1). Our results suggested that these
differences could be due to changes in the readiness with which patients
attribute the subjective feeling of fluency to pre-exposure when an alternative
explanation is available (i.e., the perceptual quality of the item). Secondly, we
explored the hypothesis that changes in attribution processes in patients with
amnesia are explained by a decrease in contingency between processing fluency and
previous occurrence of stimuli in patients' daily lives, leading them to consider
that fluency is not a relevant cue for memory (Experiment 2). Specifically, 42
healthy participants were put either in a condition where the positive
contingency between fluent processing and previous encounters with an item was
systematically confirmed (classic condition) or in a condition where the
classical association between fluency and prior exposure was systematically
reversed (reversed condition). Results indicated that participants more readily
attribute fluency to the alternative external source than to past experience in
the reversed condition than in the classic condition, mimicking the pattern of
results shown by participants with amnesia in Experiment 1. Implications of these
findings are discussed.
PMID- 28495598
TI - Mental arithmetic in the bilingual brain: Language matters.
AB - How do bilinguals solve arithmetic problems in each of their languages? We
investigated this question by exploring the neural substrates of mental
arithmetic in bilinguals. Critically, our population was composed of a
homogeneous group of adults who were fluent in both of their instruction
languages (i.e., German as first instruction language and French as second
instruction language). Twenty bilinguals were scanned with fMRI (3T) while
performing mental arithmetic. Both simple and complex problems were presented to
disentangle memory retrieval occuring in very simple problems from arithmetic
computation occuring in more complex problems. In simple additions, the left
temporal regions were more activated in German than in French, whereas no brain
regions showed additional activity in the reverse constrast. Complex additions
revealed the reverse pattern, since the activations of regions for French
surpassed the same computations in German and the extra regions were located
predominantly in occipital regions. Our results thus highlight that highly
proficient bilinguals rely on differential activation patterns to solve simple
and complex additions in each of their languages, suggesting different solving
procedures. The present study confirms the critical role of language in
arithmetic problem solving and provides novel insights into how highly proficient
bilinguals solve arithmetic problems.
PMID- 28495599
TI - Effects of the Brain-Derived Neurotrophic Factor Val66Met polymorphism and
resting brain functional connectivity on individual differences in tactile
cognitive performance in healthy young adults.
AB - Cognitive processes involve input from multiple sensory modalities and obvious
differences in the level of cognitive function can be observed between
individuals. Evidence to date understanding the biological basis of tactile
cognitive variability, however, is limited compared with other forms of sensory
cognition. Data from auditory and visual cognition research suggest that
variations in both genetics and intrinsic brain function might contribute to
individual differences in tactile cognitive performance. In the present study, by
using the tactual performance test (TPT), a widely used neuropsychological
assessment tool, we investigated the effects of the brain-derived neurotrophic
factor (BDNF) Val66Met polymorphism and resting-state brain functional
connectivity (FC) on interindividual variability in TPT performance in healthy,
young Chinese adults. Our results showed that the BDNF genotypes and resting
state FC had significant effects on the variability in TPT performance, together
accounting for 32.5% and 19.1% of the variance on TPT total score and Memory
subitem score respectively. Having fewer Met alleles, stronger anticorrelations
between left posterior superior temporal gyrus and somatosensory areas (right
postcentral gyrus and right parietal operculum cortex), and greater positive
correlation between left parietal operculum cortex and left central opercular
cortex, all correspond with better performance of TPT task. And FC between left
parietal operculum cortex and left central opercular cortex might be a mediator
of the relationship between BDNF genotypes and Memory subitem score. These data
demonstrate a novel contribution of intrinsic brain function to tactile cognitive
capacity, and further confirm the genetic basis of tactile cognition. Our
findings might also explain the interindividual differences in cognitive ability
observed in those who are blind and/or deaf from a new perspective.
PMID- 28495600
TI - The effect of cortical and subcortical lesions on spontaneous expression of
memory-encoded and emotionally infused information: Evidence for a role of the
ventral stream.
AB - The ventral stream of language processing has been implicated in the spontaneous
expression of memory-encoded and emotionally infused information. The present
study investigated whether left hemispheric lesions in post-stroke right-handed
aphasic patients may be selectively associated with specific language functions.
Speech rate was assessed with two tasks, one based on autobiographical memory of
an emotionally infused event (stroke story narration) and the other based on
information that is visually available at the time of speech generation ("cookie
theft" picture description). CT and/or MRI scans were obtained for each patient
and lesions located in 16 regions of the left hemisphere were identified and
coded. The total number of cortical and subcortical areas affected served as a
measure of lesion extent. While mean speech rates were similar across conditions,
there were different patterns of association between each index and specific
lesion sites. Non-parametric quantile regression statistical models constructed
to assess dependence of both speech rate indices on each lesion locus indicated
that the speech rate in the stroke story had significant inverse associations
with total number of lesioned areas, as well as lesions in the inferior frontal
gyrus and the external/extreme capsule region. The cookie theft speech rate had
significant inverse associations with total number of lesioned areas as well as
lesion in the inferior frontal gyrus, but not with the external/extreme capsule
region. In sum, integrity of the extreme/external capsule region appears to be
important selectively for the Stroke Story task, supporting the hypothesis that
the ventral stream plays a central role in spontaneous expression of memory
encoded and emotionally infused information.
PMID- 28495601
TI - Structural connectivity subserving verbal fluency revealed by lesion-behavior
mapping in stroke patients.
AB - Tests of verbal fluency have been widely used to assess the cognitive functioning
of persons, and are typically classified into two categories (semantic and
phonological fluency). While widely-distributed divergent and convergent brain
regions have been found to be involved in semantic and phonological fluency, the
anatomical connectivity underlying the fluency is not well understood. The
present study aims to construct a comprehensive white-matter network associated
with semantic and phonological fluency by investigating the relationship between
the integrity of 22 major tracts in the whole brain and semantic fluency
(measured by 3 cues) and phonological fluency (measured by 2 cues) in a group of
51 stroke patients. We found five left-lateralized tracts including the anterior
thalamic radiation (ATR), inferior fronto-occipital fasciculus (IFOF), uncinate
fasciculus (UF), superior longitudinal fasciculus (SLF) and frontal aslant tract
(FAT) were significantly correlated with the scores of both semantic and
phonological fluencies. These effects persisted even when we ruled out the
influence of potential confounding factors (e.g., total lesion volume). Moreover,
the damage to the first three tracts caused additional impairments in the
semantic compared to the phonological fluency. These findings reveal the white
matter neuroanatomical connectivity underlying semantic and phonological fluency,
and deepen the understanding of the neural network of verbal fluency.
PMID- 28495602
TI - A review of traditional uses, phytochemistry and pharmacology of Portulaca
oleracea L.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Portulaca oleracea L. is a widespread medicinal
plant that is used not only as an edible plant, but also as a traditional
medicine for alleviating a wide spectrum of diseases. It is a well-known plant in
the European Traditional Medicine. PA is mentioned by Dioscorides (40-90 CE),
with the name of "andrachne". AIM OF THE REVIEW: In this study, we provide
detailed information on botany, traditional uses, phytochemistry, pharmacological
uses, pharmacokinetics and safety of P. oleracea. MATERIALS AND METHODS: An
extensive search on electronic databases including PubMed, Web of Science, Google
Scholar, ScienceDirect, Scopus, conference papers, local herbal encyclopedias,
articles, books (in English, French, Arabic, Persian, etc.) and also a number of
unpublished handwritten manuscripts was done to find articles have been published
between 1956 and 2015 on pharmacology and phytochemistry of P. oleracea. RESULTS:
P. oleracea has been addressed in De Materia Medica as an astringent, and a
remedy for headaches, inflammation of the eyes and other organs, burning of the
stomach, erysipela, disorders of the bladder, numbness of the teeth, excessive
sexual desire, burning fevers, worms, dysentery, hemorrhoids, eruptions of blood,
and bites. Phytochemical investigations revealed that this plant a wide range of
secondary metabolites including alkaloids, terpenoids, flavonoids and organic
acids. The most important pharmacological activities are renoprotective
activities and effects on metabolism. P. oleracea could successfully decrease
blood glucose and lipid profile of patients with metabolic syndrome. The safety
of P. oleracea has been reported in many clinical trials. CONCLUSION: Modern
pharmacological studies have now proven many traditional uses of P. oleracea,
including anti-hyperglycemic and anti-hyperlipidemic, renoprotective and
hepatoprotective effects. In addition, in many clinical trials P. oleracea showed
no adverse effects and constipation was reported as the most frequent adverse
effect.
PMID- 28495603
TI - Ethnopharmacological uses, phytochemistry, biological activities, and therapeutic
applications of Clinacanthus nutans (Burm. f.) Lindau: A comprehensive review.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Clinacanthus nutans (Burm. f.) Lindau, a widely
used medicinal plant, is extensively grown in tropical Asia and Southeast Asian
countries. C. nutans, with its broad spectrum of pharmacological activities, has
been traditionally used to treat cancer, inflammatory disorders, diabetes, insect
bites, and skin problems, consumed as a vegetable, mixed with fresh juices, in
concoctions, and as a whole plant. The present review analyzes the advances in
the ethnopharmacology, phytochemistry, pharmacology, and toxicology of C. nutans.
In addition, the needs and perspectives for future investigation of this plant
are addressed. AIM OF THE REVIEW: This review aims to provide a comprehensive
report on the ethnomedicinal use, phytochemistry, pharmacological activities,
molecular mechanisms, and nutritional values of C. nutans. The present review
will open new avenues for further in-depth pharmacological studies of C. nutans
for it to be developed as a potential nutraceutical and to improve the available
products in the market. MATERIAL AND METHODS: All the available information on C.
nutans was collected using the key words "Clinacanthus nutans" and/or
"ethnomedicine" and/or "phytochemicals" and/or "anticancer" and/or "anti
inflammatory" and/or "antiviral" through an electronic search of the following
databases: PubMed, Web of Science, EMBASE, Cochrane Library, Clinical Trials.org,
SciFinder Scholar, Scopus, and Google Scholar. In addition, unpublished
materials, Ph.D. and M.Sc. dissertations, conference papers, and ethnobotanical
textbooks were used. The Plant List (www.theplantlist.org) and International
Plant Name Index databases were used to validate the scientific name of the
plant. RESULTS: The literature supported the ethnomedicinal uses of C. nutans as
recorded in Thailand, Indonesia, and Malaysia for various purposes. Bioactivities
experimentally proven for C. nutans include cytotoxic, anticancer, antiviral,
anti-inflammatory, immunomodulatory, antidiabetic, antioxidant,
antihyperlipidemic, antimicrobial, and chemotherapeutic (in aquaculture)
activities. Most of these activities have so far only been investigated in
chemical, cell-based, and animal assays. Various groups of phytochemicals
including five sulfur-containing glycosides, eight chlorophyll derivatives, nine
cerebrosides, and a monoacylmonogalactosyl glycerol are present in C. nutans. The
presence of two glycerolipids, four sulfur-containing compounds, six known
flavones, a flavanol, four flavonols, two phytosterols, one polypeptide, and
various phenolics and fatty acids largely influences its diverse bioactivities.
Numerous reports justify the ethnomedicinal use of C. nutans as an antiviral
agent in treating herpes simplex virus and varicella-zoster virus infections and
as part of a traditional anticancer anti-inflammatory concoction agent for
various inflammatory diseases. C. nutans tea was reported to have a good
percentage of carbohydrate, crude protein, minerals, essential amino acids,
nonessential amino acids, and essential fatty acids. Acute, subacute, and
subchronic toxicity studies demonstrated that oral administration of ethanol and
methanol extracts of C. nutans to male Swiss albino mice and male Sprague-Dawley
(SD) rats, respectively, did not lead to any toxicity or adverse effects on the
animal behavior and organs when used in amounts as high as 2g/kg. CONCLUSION: The
collected literatures demonstrated that, as an important traditional medicine, C.
nutans is a promising ethnomedicinal plant with various extracts and bioactive
compounds exhibiting multifarious bioactivities. However, it is important for
future studies to conduct further in vitro and in vivo bioactivity evaluations
systematically, following the standard pharmacology guidelines. It is crucial to
elucidate in-depth molecular mechanisms, structure-activity relationships, and
potential synergistic and antagonistic effects of multi-component extracts and
bioactive constituents derived from C. nutans. Further studies should also focus
on comprehensive toxicity that includes long-term effects and adverse effects on
target organs of C. nutans and bioactive compounds in correlation with the
specific pharmacological effects.
PMID- 28495604
TI - Conditioning with spatio-temporal patterns: Constraining the contribution of the
hippocampus to configural learning.
AB - The conditions under which the hippocampus contributes to learning about spatio
temporal configural patterns are not fully established. The aim of Experiments 1
4 was to investigate the impact of hippocampal lesions on learning about where or
when a reinforcer would be delivered. In each experiment, the rats received
exposure to an identical set of patterns (i.e., spotted+morning, checked+morning,
spotted+afternoon and checked+afternoon); and the contexts (Experiment 1), times
of day (Experiment 2), or their configuration (Experiments 3 and 4) signalled
whether or not a reinforcer would be delivered. The fact that hippocampal damage
did not disrupt the formation of simple or configural associations involving
spatio-temporal patterns is surprising, and suggests that the contribution of the
hippocampus is restricted to mediated learning (or updating) involving spatio
temporal configurations.
PMID- 28495605
TI - Inactivation of basolateral amygdala prevents chronic immobilization stress
induced memory impairment and associated changes in corticosterone levels.
AB - Chronic stress causes detrimental effects on various forms of learning and
memory. The basolateral amygdala (BLA) not only plays a crucial role in mediating
certain forms of memory, but also in the modulation of the effects of stress.
Chronic immobilization stress (CIS) results in hypertrophy of the BLA, which is
believed to be one of the underlying causes for stress' effects on learning.
Thus, it is plausible that preventing the effects of CIS on amygdala would
preclude its deleterious cognitive effects. Accordingly, in the first part, we
evaluated the effect of excitotoxic lesion of the BLA on chronic stress-induced
hippocampal-dependent spatial learning using a partially baited radial arm maze
task. The BLA was ablated bilaterally using ibotenic acid prior to CIS.
Chronically stressed rats showed impairment in spatial learning with decreased
percentage correct choice and increased reference memory errors. Excitotoxic
lesion of the BLA prevented the impairment in spatial learning and reference
memory. In the retention test, lesion of the BLA was able to rescue the chronic
stress-induced impairment. Interestingly, stress-induced enhanced plasma
corticosterone levels were partially prevented by the lesion of BLA. These
results motivated us to evaluate if the same effects can be observed with
temporary inactivation of BLA, only during stress. We found that chronic stress
induced spatial learning deficits were also prevented by temporary inactivation
of the BLA. Additionally, temporary inactivation of BLA partially precluded the
stress-induced increase in plasma corticosterone levels. Thus, inactivation of
BLA precludes stress-induced spatial learning deficits, and enhanced plasma
corticosterone levels. It is speculated that BLA inactivation-induced reduction
in corticosterone levels during stress, might be crucial in restoring spatial
learning impairments. Our study provides evidence that amygdalar modulation
during stress might be beneficial for strategic management of stress-related
cognitive deficits.
PMID- 28495606
TI - The synthetic cannabinoid WIN-55,212 induced-apoptosis in cytotrophoblasts cells
by a mechanism dependent on CB1 receptor.
AB - The endocannabinoid system has evolved as a key regulator in several pathological
and physiological processes, including placentation, decidualization and
implantation. In addition, it is known that Cannabis and cannabinoids negatively
affect female reproduction. Although, the biological action of synthetic
cannabinoids, such as WIN-55,212, in human fertility and pregnancy outcome remain
to be unveiled. A tight balance between proliferation, differentiation and
apoptosis of trophoblast cells is required for placental development and
pregnancy outcome. Therefore, in this work, the effects of the synthetic
cannabinoid WIN-55,212 in placental cytotrophoblast cells were explored. For
that, it was used a human choriocarcinoma cell line, BeWo cells, and primary
cultures of human cytotrophoblasts isolated from term placentas. Results
demonstrate that this synthetic cannabinoid induces cell cycle arrest. We also
observed that cell viability loss was associated with a disruption of
mitochondrial membrane potential and activation of caspases -9 and -3/-7
independently of reactive oxygen species (ROS) production or recruitment of the
endoplasmic reticulum stress marker CHOP. Moreover, these effects were prevented
by pre-incubation with a selective cannabinoid receptor 1 (CBR1) antagonist
(AM281). Thus, our results provide strong evidences of the apoptotic process
induced by WIN-55,212 through the activation of the CBR1, which may reveal the
impact of cannabinoids consumption during placental development.
PMID- 28495607
TI - Prenatal exposure to lambda-cyhalothrin alters brain dopaminergic signaling in
developing rats.
AB - The present study is focused to decipher the molecular mechanisms associated with
dopaminergic alterations in corpus striatum of developing rats exposed prenatally
to lambda-cyhalothrin (LCT), a new generation type II synthetic pyrethroid. There
was no significant change in the mRNA and protein expression of DA-D1 receptors
at any of the doses of LCT (0.5, 1 and 3mg/kg body weight) in corpus striatum of
developing rats exposed prenatally to LCT on PD22 and PD45. Prenatal exposure to
LCT (1 and 3mg/kg body weight) resulted to decrease the levels of mRNA and
protein of DA-D2 receptors in corpus stratum of developing rats on PD22 as
compared to controls. Decrease in the binding of 3H-Spiperone in corpus striatum,
known to label DA-D2 receptors was also distinct in developing rats on PD22.
These rats also exhibited decrease in the expression of proteins - TH, DAT and
VMAT2 involved in pre-dopaminergic signaling. Further, decrease in the expression
of DARPP-32 and pCREB associated with increased expression of PP1alpha was
evident in developing rats on PD22 as compared to controls. Interestingly, a
trend of recovery in the expression of these proteins was observed in developing
rats exposed to LCT at moderate dose (1.0mg/kg body weight) while alteration in
the expression of these proteins continued to persist in those exposed at high
dose (3.0mg/kg body weight) on PD45 as compared to respective controls. No
significant change in the expression of any of these proteins was observed in
corpus striatum of developing rats prenatally exposed to LCT at low dose
(0.5mg/kg body weight) on PD22 and PD45 as compared to respective controls. The
results provide interesting evidence that alterations in dopaminergic signaling
on LCT exposure are due to selective changes in DA-D2 receptors in corpus
striatum of developing rats. Further, these changes could be attributed to
impairment in spontaneous motor activity on LCT exposure in developing rats.
PMID- 28495608
TI - Short-term caloric restriction exerts neuroprotective effects following mild
traumatic brain injury by promoting autophagy and inhibiting astrocyte
activation.
AB - Cognitive deficits may occur after mild traumatic brain injury (mTBI), but
effective treatment modalities are presently unavailable. Caloric restriction
(CR) has beneficial effects on neurodegenerative diseases and brain injury.
However, the underlying mechanisms have not yet been clearly defined. Therefore,
the aim of the present study was to investigate the short-term effects of CR
treatment on cognitive function in mice after mTBI. Forty-five 12-week-old
C57/BL6 mice were subjected to closed-head mTBI using a weight drop device. The
mice were then randomly divided into three groups according to their diet for 30
days: the normal calorie group (mTBI+NC group, n=15), the caloric restriction
group (mTBI+CR group, n=15), and the high energy group (mTBI+HE group, n=15).
After 30 days, the Morris water maze test was performed to evaluate learning
abilities. Nissl staining, immunohistochemistry, and western blotting were used
to monitor pathological changes and changes in autophagy-associated proteins in
the hippocampus. The average escape latency was significantly shorter in the
mTBI+CR group than in the mTBI+NC and mTBI+HE groups, and the number of target
platform crossings in the mTBI+CR group was significantly higher than in the
other two groups. In the hippocampus, the expression of GFAP and mTOR was
increased in the mTBI+HE group and decreased in the mTBI+CR group. Conversely,
the expression of LC3B was decreased in the mTBI+HE group and increased in the
mTBI+CR group. Our findings suggest that short-term CR after mTBI may ameliorate
cognitive dysfunction induced by mTBI by increasing the level of autophagy and
suppressing astrocyte activation.
PMID- 28495609
TI - Acute low-level alcohol consumption reduces phase locking of event-related
oscillations in rodents.
AB - Event-related oscillations (EROs) are rhythmic changes that are evoked by a
sensory and/or cognitive stimulus that can influence the dynamics of the EEG.
EROs are defined by the decomposition of the EEG signal into magnitude (energy)
and phase information and can be elicited in both humans and animals. EROs have
been linked to several relevant genes associated with ethanol dependence
phenotypes in humans and are altered in selectively bred alcohol-preferring rats.
However, pharmacological studies are only beginning to emerge investigating the
impact low intoxicating doses of ethanol can have on event-related neural
oscillations. The main goal of this study was to investigate the effects of low
levels of voluntary consumption of ethanol, in rats, on phase locking of EROs in
order to give further insight into the acute intoxicating effects of ethanol on
the brain. To this end, we allow rats to self-administer unsweetened 20% ethanol
over 15 intermittent sessions. This method results in a stable low-dose
consumption of ethanol. Using an auditory event-related potential "oddball"
paradigm, we investigated the effects of alcohol on the phase variability of EROs
from electrodes implanted into the frontal cortex, dorsal hippocampus, and
amygdala. We found that intermittent ethanol self-administration was sufficient
to produce a significant reduction in overall intraregional synchrony across all
targeted regions. These data suggest that phase locking of EROs within brain
regions known to be impacted by alcohol may represent a sensitive biomarker of
low levels of alcohol intoxication.
PMID- 28495610
TI - "Allergic mood" - Depressive and anxiety symptoms in patients with seasonal
allergic rhinitis (SAR) and their association to inflammatory, endocrine, and
allergic markers.
AB - A growing number of studies show an association between seasonal allergic
rhinitis (SAR) with depression and anxiety. The underlying mechanisms of a link
between SAR and affect, however, are still unclear. The objective of the present
study was to investigate depressive symptoms and anxiety in SAR patients and
their association to inflammatory and endocrine parameters. SAR patients (n=41)
and non-allergic, healthy controls (n=42) were assessed during (pollen season)
and out of symptomatic periods (non-pollen season). Inflammatory cytokine profile
(Interleukin [IL]-2, IL-4, IL-6, IL-8, IL-10, IL-17, IFN-gamma, TNF-alpha),
Immunoglobulin-E (IgE), hair cortisol concentrations (HCC), as well as sleep
quality were measured. The present data show that during acute allergic
inflammation SAR patients experienced a significant increase in Beck Depression
Inventory (BDI-) II scores when (a) compared to the asymptomatic period and (b)
when compared to the non-allergic controls, while no differences in anxiety were
observed. Increased BDI-II scores in SAR patients were significantly associated
with levels of IL-6 as well as IL-6/IL-10 and IFN-gamma/IL-10 ratios and further,
to an early age at manifestation of SAR and poor sleep quality. These findings
support a close relationship between acute allergic processes and affective
states, with inflammatory cytokines, sleep, and age of manifestation as
potentially relevant mediators.
PMID- 28495612
TI - Effect of infrared light on live blood cells: Role of beta-carotene.
AB - We have utilized Raman tweezers to measure and assign micro-Raman spectra of
optically trapped, live red blood cells (RBCs), white blood cells (WBCs) and
platelets. Various types of WBCs- both granulocytes, lymphocytes, and their
different types have been studied. The Raman bands are assigned to different
biomolecules of blood cells. The Raman spectra thus obtained has been enabled
detection of beta-carotene in these blood cells, the spectral features of which
act as a signature that facilitates experimental probing of the effect of 785nm
laser light on different blood cells as a function of incident laser power in the
mW range. The spectral changes that we obtain upon laser irradiation indicate
that, both haemoglobin as well as the cell membrane sustains damage. In case of
lymphocytes and platelets the peaks corresponding to beta-carotene showed drastic
changes. Thorough analysis of the spectral changes indicates possibility of free
radical induced damage of beta-carotene in lymphocytes and platelets. Among
different blood cells, RBCs have a power threshold of only 10mW. The power
threshold for other types of blood cells is somewhat higher, but always below
about 30mW. These values are likely to serve as useful guides for Raman tweezers
based experiments on live cells.
PMID- 28495611
TI - HIV-1 TAT protein enhances sensitization to methamphetamine by affecting
dopaminergic function.
AB - Methamphetamine abuse is common among humans with immunodeficiency virus (HIV).
The HIV-1 regulatory protein TAT induces dysfunction of mesolimbic dopaminergic
systems which may result in impaired reward processes and contribute to
methamphetamine abuse. These studies investigated the impact of TAT expression on
methamphetamine-induced locomotor sensitization, underlying changes in dopamine
function and adenosine receptors in mesolimbic brain areas and neuroinflammation
(microgliosis). Transgenic mice with doxycycline-induced TAT protein expression
in the brain were tested for locomotor activity in response to repeated
methamphetamine injections and methamphetamine challenge after a 7-day abstinence
period. Dopamine function in the nucleus accumbens (Acb) was determined using
high performance liquid chromatography. Expression of dopamine and/or adenosine A
receptors (ADORA) in the Acb and caudate putamen (CPu) was assessed using RT-PCR
and immunohistochemistry analyses. Microarrays with pathway analyses assessed
dopamine and adenosine signaling in the CPu. Activity-dependent neurotransmitter
switching of a reserve pool of non-dopaminergic neurons to a dopaminergic
phenotype in the ventral tegmental area (VTA) was determined by
immunohistochemistry and quantified with stereology. TAT expression enhanced
methamphetamine-induced sensitization. TAT expression alone decreased striatal
dopamine (D1, D2, D4, D5) and ADORA1A receptor expression, while increasing
ADORA2A receptors expression. Moreover, TAT expression combined with
methamphetamine exposure was associated with increased adenosine A receptors
(ADORA1A) expression and increased recruitment of dopamine neurons in the VTA.
TAT expression and methamphetamine exposure induced microglia activation with the
largest effect after combined exposure. Our findings suggest that dopamine
adenosine receptor interactions and reserve pool neuronal recruitment may
represent potential targets to develop new treatments for methamphetamine abuse
in individuals with HIV.
PMID- 28495613
TI - Mode of action and human relevance of THF-induced mouse liver tumors.
AB - In a National Toxicology Program (NTP) bioassay, inhalation of tetrahydrofuran
(THF) induced liver tumors in female B6C3F1 mice but not in male mice or rats of
either sex. Since THF is not genotoxic, the NTP concluded this carcinogenic
activity was likely mediated via non-genotoxic modes of action (MOA). Based on
evidence that THF and phenobarbital share a similar MOA, female Car/Pxr knock-out
mice were orally exposed to THF to evaluate the potential role of CAR activation
in the MOA for THF-induced liver tumors. Because data from this oral study with
Car/Pxr knock-out mice (C57Bl/6) and the inhalation studies with wild type mice
(B6C3F1) reported by NTP and others were derived from different strains, oral
studies with wild type B6C3F1 and C57Bl/6 mice were conducted to ensure THF
responses in both strains were comparable. As seen in inhalation studies with
THF, oral exposure of wild type female mice to a maximum tolerated dose of THF
increased total P450 content, CAR-related P450 activities, and hepatocyte
proliferation; these effects were not observed in Car/Pxr knock-out female mice.
This finding supports the hypothesis THF-induced carcinogenicity is likely
mediated via CAR activation that has limited, if any, relevance to humans.
PMID- 28495614
TI - Protective potential of different compounds and their combinations with MESNA
against sulfur mustard-induced cytotoxicity and genotoxicity.
AB - The purpose of this study was to evaluate the efficacy of potential candidate
molecules or their combinations against strong alkylation agent sulfur mustard
(SM) on the human lung alveolar epithelial cell line A-549. Candidate molecules
were chosen on the basis of their previously observed protective effects in
vitro. The tested compounds, including antioxidants, sulfhydryl or other sulfur
containing molecules, nitrogen-containing molecules, PARP inhibitors and a NO
synthase inhibitor, were applicated 30min before SM treatment. The efficiency of
candidate molecules to protect cells against DNA damage and cell death induced by
SM was determined using single-cell gel electrophoresis (comet assay) and 3-(4,5
dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction by viable
cells. The damage of DNA was assessed 1 and 24h after dose 50MUM SM. Cell
survival was assessed 24 and 72h after the exposure. To achieve maximal
cytoprotection, combinations of selected compounds with sodium 2-mercaptoethane
sulphonate (MESNA) were tested. We found significant protective effects by
several drugs used individually and also in combination with MESNA. High
protection was achieved by sodium thiosulphate, which was further potentiated
when combined with MESNA. Most of the selected compounds or mixture provided only
moderate genoptotection without having any effect towards cell viability.
PMID- 28495615
TI - A novel function of TLR4 in mediating the immunomodulatory effect of
Benzanthrone, an environmental pollutant.
AB - Our prior studies have reported that Benzanthrone (BA) manifests inflammatory
responses in the spleen of Balb/c mice. The present investigation was carried out
to study the impact of BA on macrophages, which are the primary scavenger cells
in the body that act as a connecting link between innate and adaptive immunity.
Parenteral administration of BA (daily for one week) to mice resulted in enhanced
levels of nitric oxide (NO) and overexpression of inflammatory markers (COX-2,
MMP-9 and PGE-2) in macrophages; however the level of MHC class-I and MHC class
II receptors were down regulated. Further, the potential membrane receptor
targets (TLRs) of BA and its interaction with TLRs was investigated using
computational methods. Professional phagocytes play pivotal roles in sensing
bacteria through pathogen-associated molecular patterns (PAMPs) by various
pathogen recognition receptors (PRRs), including Toll-like receptors (TLRs).
Several studies have implicated these TLRs in the amplification of the
inflammatory responses, however the fundamental role played by TLRs in mediating
the inflammation associated with xenobiotics is still obscure and not understood.
From the in silico analysis, it was evident that BA showed the highest binding
affinity with TLR4 as compared to other TLRs. The western blotting studies
confirmed that BA exposure indeed upregulated the expression of TLR 4, 5 and 9.
Moreover, the downstream signaling cascade proteins of TLRs such as myeloid
differentiation primary response protein-88 (MyD88), IL-1 receptor associated
kinase (IRAK-1), and TNFR-associated factor (TRAF-6) were found to be enhanced in
the BA treated groups. It was also observed that BA treatment increased the
expression of ICAM-1, p-Lyn, p-Syk, p-PI3-K, IP3, PLC-gamma, cAMP and Ca+2
influx, which are known to play a critical role in TLR mediated inflammation.
Earlier we found that toxic effects of BA in spleen were mediated by oxidative
stress which was partially neutralized by NAC exposure. Hereby, we report that
NAC treatment in conjunction with BA attenuated the expression of BA induced
TLR4, as well as the inflammatory markers such as COX2 and p-NFkB in macrophages.
These findings demonstrated the critical role of TLRs in the regulation of the BA
induced inflammation.
PMID- 28495616
TI - Salvianolic acid B attenuates doxorubicin-induced ER stress by inhibiting TRPC3
and TRPC6 mediated Ca2+ overload in rat cardiomyocytes.
AB - Doxorubicin (DOX)-induced cardiotoxicity is a clinically complex syndrome that
leads to significant pain to cancer survivors. Endoplasmic reticulum (ER) stress
has been suggested to be an important contributor to myocardium dysfunction
during this phenomenon. Our previous study proved that Salvianolic acid B (Sal B)
protected against doxorubicin induced cardiac dysfunction by inhibiting ER stress
and cardiomyocyte apoptosis. However, the underlying molecular mechanism is not
yet clearly. In this study, we investigated the protective effect and mechanisms
of Sal B againest DOX-induced cardiac injury and ER stress in vivo and in vitro.
After pretreatment with Sal B (0.25, 0.5, 1mg/kg i.v.) for 7 days, male SD rats
were intraperitoneally injected with a single dose of DOX (3mg/kg) every 2 days
for three injections. The cardioprotective effect of Sal B was observed 2 weeks
after the first administration. Adult rat ventricular myocytes were isolated and
treated with Sal B (20MUg/ml) for 6h and then exposed in DOX (1MUm) for 4h. The
cardiomyocyte contractility and the level of intracellular Ca2+ were determined.
Sal B ameliorated DOX-induced apoptosis damage in heart tissues. In vitro studies
showed that DOX induced adult rat ventricular myocytes contractile dysfunction
and intracellular Ca2+ handling derangement, disrupted mitochondrial membrane
potential, raised the level of ER stress related proteins. However, Sal B
pretreatment suppressed all of these adverse effects of DOX. The effects of Sal B
were closely related to the inhibition of transient receptor potential canonical
(TRPC) channels, as characterized by inhibiting the expression of TRPC 3 and
TRPC6. These results indicate that Sal B protects against DOX-induced cardiac
apoptosis and ER stress via TRPC3 and TRPC6 inhibition.
PMID- 28495617
TI - The adaptor protein ARA55 and the nuclear kinase HIPK1 assist c-Myb in recruiting
p300 to chromatin.
AB - LIM-domain proteins, containing multiple cysteine-rich zinc finger-like motifs,
have been shown to play diverse roles in several cellular processes. A common
theme is that they mediate important protein-protein interactions that are key to
their function. Androgen receptor-associated protein 55 (ARA55) belongs to this
family of bridging proteins containing four C-terminal LIM domains. It has a dual
role with functions both at focal adhesions and in the nucleus, apparently
shuttling between the two compartments. In the present work, we have expanded our
understanding of its nuclear functions by showing that it interacts with three
nuclear regulators not previously linked to ARA55. We first identified ARA55 as a
novel interaction partner of the nuclear kinase HIPK1 and found that ARA55, like
HIPK1, also interacts with the transcription factor c-Myb. In search of a
function for these associations, we observed that the coactivator p300 not only
binds to c-Myb, but to ARA55 as well. When combined, c-Myb, p300, HIPK1 and ARA55
caused strong synergistic activation of a chromatinized reporter gene. In
parallel, all partners, including p300, were efficiently recruited to chromatin
at the c-Myb-bound promoter. Consistent with this cooperation, we found that c
Myb and ARA55 share a common set of target genes in an osteosarcoma cellular
context. We propose that ARA55 and HIPK1 assist c-Myb in recruiting the
coactivator and acetyltransferase p300 to chromatin.
PMID- 28495618
TI - A model of acute renal allograft rejection in outbred Yorkshire piglets.
AB - Pigs represent a desirable animal model for the study of rejection in kidney
transplantation with inbred Yucatan miniature swine (YMS) the most commonly
studied strain due to well defined swine leukocyte antigen (SLA) genotypes.
However, limitations to YMS may include cost and availability. Outbred Yorkshire
pigs are widely available and significantly cheaper than YMS. Recent advances in
SLA genotyping have allowed its application to outbred strains. On this basis, we
theorized that Yorkshire pigs would be a viable alternative to YMS for the study
of rejection in kidney transplantation. To address this question, we performed
auto (Auto) and allotransplants (Allo) in 24 Yorkshire pigs, and assessed SLA
genotypes and acute rejection after 72h. At sacrifice, and when compared to
autotransplants, allotransplants had significant elevations in serum creatinine
(8.4+/-1.3 vs 2.8+/-2.0mg/dL for Allo vs autotransplants, respectively) and BUN
(61+/-9 vs 19.2+/-15mg/dL for Allo vs autotransplants, respectively). Warm
ischemia times between the two groups did not differ (24+/-2.3 vs 26.4+/-1.4min
for Auto vs Allo, respectively). There were 16 distinct SLA haplotypes identified
from pigs undergoing allotransplantion, no matched donor-recipient pairs, and all
allografts demonstrated rejection. Type IIA cellular rejection (Banff) was the
most common. One allograft demonstrated hyperacute rejection due a blood group
incompatibility. Histologically, the expression of regulatory Tcells and
dendritic cells was increased in allografts. These data suggest that Yorkshire
pigs may be a useful model for the study of acute rejection in experimental
kidney transplantation.
PMID- 28495619
TI - The RESPIRE trials: Two phase III, randomized, multicentre, placebo-controlled
trials of Ciprofloxacin Dry Powder for Inhalation (Ciprofloxacin DPI) in non
cystic fibrosis bronchiectasis.
AB - : The primary goals of long-term disease management in non-cystic fibrosis
bronchiectasis (NCFB) are to reduce the number of exacerbations, and improve
quality of life. However, currently no therapies are licensed for this.
Ciprofloxacin Dry Powder for Inhalation (Ciprofloxacin DPI) has potential to be
the first long-term intermittent therapy approved to reduce exacerbations in NCFB
patients. The RESPIRE programme consists of two international phase III
prospective, parallel-group, randomized, double-blinded, multicentre, placebo
controlled trials of the same design. Adult patients with idiopathic or post
infectious NCFB, a history of >=2 exacerbations in the previous 12months, and
positive sputum culture for one of seven pre-specified pathogens, undergo
stratified randomization 2:1 to receive twice-daily Ciprofloxacin DPI 32.5mg or
placebo using a pocket-sized inhaler in one of two regimens: 28days on/off
treatment or 14days on/off treatment. The treatment period is 48weeks plus an 8
week follow-up after the last dose. The primary efficacy endpoints are time to
first exacerbation after treatment initiation and frequency of exacerbations
using a stringent definition of exacerbation. Secondary endpoints, including
frequency of events using different exacerbation definitions, microbiology,
quality of life and lung function will also be evaluated. The RESPIRE trials will
determine the efficacy and safety of Ciprofloxacin DPI. The strict entry criteria
and stratified randomization, the inclusion of two treatment regimens and a
stringent definition of exacerbation should clarify the patient population best
positioned to benefit from long-term inhaled antibiotic therapy. Additionally
RESPIRE will increase understanding of NCFB treatment and could lead to an
important new therapy for sufferers. TRIAL REGISTRATION: The RESPIRE trials are
registered in ClinicalTrials.gov, ID number NCT01764841 (RESPIRE 1; date of
registration January 8, 2013) and NCT02106832 (RESPIRE 2; date of registration
April 4, 2014).
PMID- 28495621
TI - A reusable multipurpose magnetic nanobiocatalyst for industrial applications.
AB - A multipurpose magnetic nanobiocatalyst is developed by conjugating Pectinex 3XL
(a commercial enzyme containing pectinase, xylanase and cellulase activities) on
3-aminopropyl triethoxysilane activated magnetic nanoparticles. The
nanobiocatalyst retained 87% of pectinase, 69% of xylanase and 58% of cellulase
activity after conjugation on modified nanoparticles as compared to their soluble
counterparts. Thermal stability data at 70 degrees C showed increase in enzyme
stability after conjugation to nanoparticles and the kinetic parameters (Km and
Vmax) remain unaltered after immobilization. The immobilized enzyme system can be
successfully used upto 5th cycle after that slight decrease in enzyme activities
was observed. The nanobiocatalyst retained high pectinase activities in organic
solvents and chemical reagents as compared to free enzymes. DLS data shows that
the nanoparticles size increases from 63nm to 86nm after immobilization. Atomic
Force Microscopy data confirms the deposition of enzymes on the nanoparticles.
The nanobiocatalyst was used for the clarification of pine apple and orange juice
and was also used for the production of bioethanol. Hydrolysis of pretreated
wheat straw produced 1.39g/l and 1.59g/l after treatment with free Pectinex 3xL
and nanobiocatalyst respectively. The concentration of bioethanol also increases
by 1.4 fold as compared to the free enzyme.
PMID- 28495622
TI - A new l-amino acid oxidase from Bothrops jararacussu snake venom: Isolation,
partial characterization, and assessment of pro-apoptotic and antiprotozoal
activities.
AB - A new l-amino acid oxidase (LAAO) from Bothrops jararacussu venom (BjussuLAAO-II)
was isolated by using a three-step chromatographic procedure based on molecular
exclusion, hydrophobicity, and affinity. BjussuLAAO-II is an acidic enzyme with
pI=3.9 and molecular mass=60.36kDa that represents 0.3% of the venom proteins and
exhibits high enzymatic activity (4884.53U/mg/mim). We determined part of the
primary sequence of BjussuLAAO-II by identifying 96 amino acids, from which 34
compose the N-terminal of the enzyme (ADDRNPLEECFRETDYEEFLEIARNGLSDTDNPK).
Multiple alignment of the partial BjussuLAAO-II sequence with LAAOs deposited in
the NCBI database revealed high similarity (95-97%) with other LAAOs isolated
from Bothrops snake venoms. BjussuLAAO-II exerted a strong antiprotozoal effect
against Leishmania amazonensis (IC50=4.56MUg/mL) and Trypanosoma cruzi
(IC50=4.85MUg/mL). This toxin also induced cytotoxicity (IC50=1.80MUg/mL) and
apoptosis in MCF7 cells (a human breast adenocarcinoma cell line) by activating
the intrinsic and extrinsic apoptosis pathways, but were not cytotoxic towards
MCF10A cells (a non-tumorigenic human breast epithelial cell line). The results
reported herein add important knowledge to the field of Toxinology, especially
for the development of new therapeutic agents.
PMID- 28495620
TI - Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function
(VCSIP): Rationale, design, and methods of a randomized, controlled trial of
vitamin C supplementation in pregnancy for the primary prevention of effects of
in utero tobacco smoke exposure on infant lung function and respiratory health.
AB - Despite strong anti-smoking efforts, at least 12% of American women cannot quit
smoking when pregnant resulting in >450,000 smoke-exposed infants born yearly.
Smoking during pregnancy is the largest preventable cause of childhood
respiratory illness including wheezing and asthma. Recent studies have shown a
protective effect of vitamin C supplementation on the lung function of offspring
exposed to in utero smoke in a non-human primate model and an initial human
trial. Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung
Function (VCSIP) is a randomized, double-blind, placebo-controlled trial to
evaluate pulmonary function at 3months of age in infants delivered to pregnant
smokers randomized to 500mg/day of vitamin C versus placebo during pregnancy.
Secondary aims evaluate the incidence of wheezing through 12months and pulmonary
function testing at 12months of age. Women are randomized between 13 and 23weeks
gestation from clinical sites in Portland, Oregon at Oregon Health & Science
University and PeaceHealth Southwest Medical Center and in Indianapolis, Indiana
at Indiana University and Wishard Hospital. Vitamin C supplementation occurs from
randomization to delivery. Monthly contact with participants and monitoring of
medical records is performed to document medication adherence, changes in smoking
and medical history, and adverse events. Pulmonary function testing of offspring
occurs at 3 and 12months of age and incidence of wheezing and respiratory illness
through 12months is captured via at least quarterly questionnaires. Ancillary
studies are investigating the impact of vitamin C on placental blood flow and DNA
methylation.
PMID- 28495623
TI - Polycaprolactone nanocomposite reinforced by bioresource starch-based
nanoparticles.
AB - Biodegradable polymer nanocomposites with bioresource starch-based nanoparticles
(SNPs) as reinforcing fillers for polycaprolactone (PCL) were prepared by melt
blending. Scanning electron microscopy observation revealed that SNPs as
spherical particles were evenly dispersed in the PCL matrix without any
aggregation even with the content of SNPs increasing to 10wt% in the
nanocomposite. Consequently, the rheological performances of PCL have been
improved efficaciously after incorporation with SNPs as well as mechanical
properties, especially with a percolation network structure of SNPs in the PCL
matrix formed. In addition, the enzymatic hydrolysis experiments showed a more
interesting behavior that the hydrolysis rates had been accelerated apparently in
the nanocomposites than that in the neat PCL as observed. Such high performance
nanocomposites may have great potential in expanding the utilization of starch
from sustainable resources and the practical application of PCL-based
biodegradable materials.
PMID- 28495624
TI - Mechanistic insight into interaction of Sodium Dodecyl Sulphate to asialylated
form of glycoprotein: A mimic of membrane protein-lipid system.
AB - The SDS-glycoprotein system is mimic of membrane protein-lipid system. Fate of
glycoprotein, conformation and the interactive forces involved in membrane milieu
are expected to be decided by the net charge on glycoprotein that may change
during acidic environment in a range of pathological states, including cancer,
stroke, and ischemia. Asialofetuin (ASF; asialylated form of glycoprotein) and
SDS interaction is studied when glycoprotein bears varying range of net charge
(i.e. at different pH's) by steady state and time-resolved spectroscopic,
calorimetric and microscopic approaches. SDS interacts differently with ASF when
protein is in cationic (at pH 2, 3 and 4) and in anionic states (pH 7.4). ASF
undergo aggregation at pH 2, 3 and 4 whereas have enhancement in alpha-helical
structure at pH 7.4 at sub-micellar concentrations of SDS. At pH 2, 3 and 4, the
positively charged ASF interacts electrostatically with negatively charged head
groups of SDS, leaving its hydrophobic tail free to interact with other protein
SDS complex and consequently lead to amyloid formation. However, at pH 7.4, the
ASF interacts hydrophobically with SDS and an increase in alpha-helical content
occurs that constrains the environment of Trp51 and consequently decreases
movement of Trp conformers.
PMID- 28495625
TI - Nickel nanoparticle synthesis using Camellia Sinensis as reducing and capping
agent: Growth mechanism and photo-catalytic activity evaluation.
AB - Recently, the biosynthesis of nanoparticle attracted the attention of scientific
community due to its simplicity, ease and eco-friendly nature. In the present
study, Camellia Sinensis (C. Sinensis) leaves extract was employed for the
synthesis of nickel nanoparticles (NiNPs). The fabricated NiNPs were
characterized by scanning electron microscopy (SEM) and energy-dispersive X-ray
(EDX) and X-ray diffraction techniques. The photocatalytic activity (PCA) was
evaluated by degrading crystal violet (CV) dye. The NiNPs size was in the range
of 43.87-48.76nm, spherical in shape and uniformly distributed with magnetization
saturation of 0.073 emu/g. The NiNPs showed promising PCA under solar light
irradiation. At optimized conditions, up to 99.5% CV dye degradation was
achieved. Results revealed that biosynthesis can be adopted for the synthesis of
NiNPs in nano-size range since it is simple, cost effective and eco-friendly in
nature versus physico-chemical methods.
PMID- 28495626
TI - Promising biocidal activity of thymol loaded chitosan silver nanoparticles (T
C@AgNPs) as anti-infective agents against perilous pathogens.
AB - The advent of biodegradable polymer-encapsulated drug nanoparticles has made an
exciting area of drug delivery research. The present study investigated novel and
simple route for synthesis of thymol loaded chitosan silver nanoparticles (T
C@AgNPs) using chitosan and thymol as reducing, capping agent respectively to
understand the therapeutic efficacy. The UV-vis spectroscopy, DLS, FT-IR, SEM,
EDS, XRD used for characterization and radical scavenging activity, anti
microbial and biocompatibility was taken to ascertain an efficacy of novel T
C@AgNPs. The T-C@AgNPs intense peak at 490nm indicates the formation of
nanoparticles and had average particle size of 28.94nm with spherical shape,
monodisperse state in water, also exhibited excellent biocompatibility of cubic
shaped pure silver element containing T-C@AgNPs. The antibacterial activity was
studied for gram positive and gram negative food-borne pathogens and effective
inhibition at 100MUgmL-1 to S. aureus, S. epidermidis, S. haemolyticus (10.08,
10.00, 11.23mm) and S. typhimurium, P. aeruginosa and S. flexneri (9.28, 9.33,
12.03mm) compared to antibiotic Streptomycin. This study revealed the efficacy
against multiple food-borne pathogens and therapeutic efficacy of T-C@AgNPs
offers a valuable contribution in the area of nanotechnology. This proved to be a
first-class novel antimicrobial material for the first time in this study.
PMID- 28495627
TI - Effects of site-specific phosphorylation on the mechanical properties of
ovalbumin-based hydrogels.
AB - An efficient one-step grafting approach was developed to modify ovalbumin (OVA)
by phosphorylation through selective reaction with the hydroxyl group of Ser and
Thr residues present in OVA. The site-specific phosphorylated conjugates were
characterized by Matrix-Assisted Laser Desorption Ionization-Time-of-Flight Mass
Spectrometry (MALDI-TOF/MS) and the results indicated that the Ser residue could
be more readily phosphorylated, and the typical phosphopeptides
264LTEWTSSNVMEER276 and 340EVVGSAEAGVDAASVSEEFR359 demonstrated the formation of
monophosphoester. Moreover, 13C NMR analysis showed that the betaCH2 of Ser acted
as a hydroxyl donor to react with sodium tripolyphosphate (STPP), and the
conjugates with variable phosphorylation sites could improve the weak network and
the resulting poor mechanical properties of ovalbumin-based hydrogels.
Furthermore, small-amplitude oscillatory measurements, creep recovery tests and
texture profile analysis of hardness and stickiness indicated that
phosphorylation can strengthen the intermolecular cross-linking of protein
molecules and produce significant influence on the rheological behavior and
texture properties, suggesting that a suitable conjugation site is essential for
the best gelation properties at a different pH. The integrated results indicate
that phosphorylation change significantly modify the viscoelastic and mechanical
properties of OVA-based hydrogels by changing molecular dynamics upon heating.
PMID- 28495628
TI - Optimization of functional nanoparticles formation in associative mixture of
water-soluble portion of Farsi gum and beta-lactoglobulin.
AB - Electrostatic interaction between beta-lactoglobulin (beta-Lg) and water-soluble
fraction of Farsi gum (WSFPG) was studied under the influence of pH, beta
Lg:WSFPG mixing ratio (MR) and total concentration (TC) through performing
various experiments such as turbidity, particle size and zeta potential
measurements. Changes in the relative viscosity during in-situ acidification were
studied at various ionic strengths. Lower amounts of absorbance and sedimentation
were observed by decreasing the MR. An increase in the TC increased the
absorbance of complexed samples. The smallest particle sizes, obtained at a same
MR (1:3), were 108 and 188nm at TCs of 0.1 and 0.3wt%, respectively. The
decreased relative viscosity upon acidification was a proof for the wrapping
phenomenon in the biopolymer mixture. A further decrease in the relative
viscosity was observed at higher ionic strength. The results of this study may
facilitate the rational design of functional nanoparticles in associative
mixtures of beta-Lg and WSFPG.
PMID- 28495629
TI - Improving stability and reusability of Rhodococcus pyridinivorans NIT-36
nitrilase by whole cell immobilization using chitosan.
AB - Immobilized enzymes have great significance for industrial processes. In this
study whole cell immobilization of Rhodococcus pyridinivorans NIT-36 has been
undertaken using chitosan microspheres as an immobilized matrix. R.
pyridinivorans NIT-36 harbors a significant intracellular enzyme nitrilase.
Chitosan microspheres were generated by supplementing chitosan with
glutaraldehyde and results, supported the porous microsphere structure via SEM.
The resultant microspheres exhibited cell immobilization capacity of 450mg/g. The
immobilized cells exhibited a considerable increase in temperature tolerance at
60 degrees C as compared to free cells. The immobilized microspheres also
demonstrated higher substrate tolerance. The immobilized nitrilase retained 80%
activity when stored at 4 degrees C for 10 days and retained 50% activity after 7
reuse cycles. It may be concluded that chitosan microspheres are a novel
immobilization agent for whole cell immobilization which enhances the stability
and reusability of nitrilase enzyme.
PMID- 28495630
TI - alpha-chymotrypsin activated and stabilized by self-assembled polypseudorotaxane
fabricated with bis-thiolated poly(ethylene glycol) and alpha-cyclodextrin:
Spectroscopic and mechanistic analysis.
AB - The self-assembled polypseudorotaxane (PPRX) fabricated with bis-thiolated
poly(ethylene glycol) (PEG) and alpha-cyclodextrin (alpha-CyD) acted as an
activator for alpha-chymotrypsin (CT) and retained the activity of CT for a long
time up to 7days. The stabilization mechanism was studied, and the interaction
between CT and PPRX was analyzed by using circular dichroism, fluorescence
spectra and X-ray powder diffraction (XRD). The bis-thiolated PEG and its
assembled PPRX with alpha-CyD exhibited the interaction with the C-terminal
region of the CT's B-chain probably through PEGylation of the surface disulfide
bridge of CT. It caused the aromatic chromophores more exposed to the hydrophilic
microenvironment, leading to conformational variation of CT that was revealed by
spectroscopic analysis. It rendered the peptide chains in a more flexible and
active state. As a comparison, the non-thiolated components could not decorate
the surface of CT and performed almost no effect on its stability, which
demonstrated that the decoration of the surface disulfide bridge was a key factor
in retaining the activity of CT. Due to the activation and stabilization effect,
bis-thiolated PEG/alpha-CyD PPRX was an excellent soft-immobilized carrier for
CT, and provided an intriguing method for enzyme's stabilization.
PMID- 28495631
TI - Synthesis and characterization of Ag2S decorated chitosan nanocomposites and
chitosan nanofibers for removal of lincosamides antibiotic.
AB - We report the synthesis of Ag2S-Chitosan nanocomposites and Ag2S-chitosan
nanohybrids as performance adsorbents for Lincosamides such as Clindamycin
antibiotic removal. Isotherms and kinetic studies were determined to understand
the adsorption behavior both two adsorbent. At low adsorbent dose, removals are
increased in the adsorption process, and performance is better with Ag2S-chitosan
nanohybrids due to the special surface area increased. The average sizes and
surface area of Ag2S-Chitosan nanocomposites and Ag2S-chitosan nanohybrids were
found as 50nm, 70nm and 180.18, 238.24m2g-1, respectively. In particular, Ag2S
Chitosan nanocomposites and Ag2S-chitosan nanohybrids show high maximum
Clindamycin adsorption capacity (qmax) of 153.21, and 181.28mgg-1, respectively.
More strikingly, Ag2S-Chitosan nanocomposites and Ag2S-chitosan nanohybrids are
also demonstrated to nearly completely remove Clindamycin from drinking water.
The excellent adsorption performance along with their cost effective, convenient
synthesis makes this range of adsorbents highly promising for commercial
applications in drinking water and wastewater treatment.
PMID- 28495632
TI - Evaluation of dermal wound healing activity and in vitro antibacterial and
antioxidant activities of a new exopolysaccharide produced by Lactobacillus
sp.Ca6.
AB - The present study aimed to evaluate the in vitro antibacterial and antioxidant
activities and the in vivo wound healing performance of a noval
exopolysaccharides (EPS-Ca6) produced by Lactobacillus sp.Ca6 strain. The results
showed that EPS-Ca6 had a potential antioxidant activity determined through four
different assays: DPPH scavenging activity, reducing power, beta-carotene
bleaching by linoleic acid assay, and Metal chelating activities. It also
exhibited significant antibacterial activity against pathogenic bacteria
Salmonella enterica and Micrococcus luteus. The wound healing activity of the EPS
Ca6, using excision wound model in rats, showed that this novel EPS accelerated
significantly wound healing activity as compared to the control group, and a
total closure was achieved after 14days of wound induction. Furthermore,
histological examination of biopsies showed fully re-epithelialized wound with a
complete epidermal regeneration. Overall the finding indicates that the EPS-Ca6
might be useful as a wound healing agent in modern medicine.
PMID- 28495633
TI - Mechanical reinforcement of gelatin hydrogel with nanofiber cellulose as a
function of percolation concentration.
AB - Given a variety of distinguished aspect ratio-related characteristics of
nanofiber cellulose (NFC), the impact of NFC on gelatin hydrogel performance
involving strength, rheology, microstructure was investigated, focusing on
concentration percolation mechanism for it. The inner topography displayed a
compact three-dimensional network structure in the NFC-added gelatin gel,
however, an NFC amount of 7.5gkg-1 caused more inhomogeneous aggregation. Texture
profile analysis showed that the addition of NFC increased the hardness but
reduced the elasticity of gelatin gel at 10 degrees C, depending on NFC
concentration. For static rheology, adding NFC transformed gelatin solution from
the Newtonian action into pseudoplastic behavior at 60 degrees C, with a marked
increase of viscosity. Furthermore, NFC improved the temperature of sol-gel
transition of gelatin, even no obvious transformation as >=5gkg-1 NFC used. NFC
reinforcement provides the potential to use as texture modifier along with
gelatin in food field.
PMID- 28495635
TI - Can we detect the effect of spines and leaflets on the diffusion of brain
intracellular metabolites?
AB - Prior models used to clarify which aspects of tissue microstructure mostly affect
intracellular diffusion and corresponding diffusion-weighted magnetic resonance
(DW-MR) signal have focused on relatively simple geometrical descriptions of the
cellular microenvironment (spheres, randomly oriented cylinders, etc...),
neglecting finer morphological details which may have an important role. Some
types of neurons present high density of spines; and astrocytes and macroglial
cells processes present leaflets, which may all impact the diffusion process.
Here, we use Monte-Carlo simulations of many particles diffusing in cylindrical
compartments with secondary structures mimicking spines and leaflets of neuronal
and glial cell fibers, to investigate to what extent the diffusion-weighted
signal of intracellular molecules is sensitive to spines/leaflets density and
length. In order to study the specificity of DW-MR signal to these kinds of
secondary structures, beading-like geometry is simulated as "control" deviation
from smooth cylinder too. Results suggest that: a) the estimated intracellular
tortuosity increases as spines/leaflets density or length (beading amplitude)
increase; b) the tortuosity limit is reached for diffusion time td>200 ms for
metabolites and td>70 ms for water molecules, suggesting that the effects of
these finer morphological details are negligible at td longer than these
threshold values; c) fiber diameter is overestimated, while intracellular
diffusivity is underestimated, when simple geometrical models based on hollow
smooth cylinders are used; d) apparent surface-to-volume, S/V, ratio estimated by
linear fit of high frequency OG data appears to be an excellent estimation of the
actual S/V ratio, even in the presence of secondary structures, and it increases
as spines and leaflets density or length increase (while decreasing as beadings
amplitude increases). Comparison between numerical simulations and multimodal
metabolites DW-MRS experiments in vivo in mouse brain shows that these fine
structures may affect the DW-MRS signal and the derived diffusion metrics
consistently with their expected density and geometrical features. This work
suggests that finer structures of cell morphology have non-negligible effects on
intracellular molecules' diffusion that may be measured by using multimodal DW
MRS approaches, stimulating future developments and applications.
PMID- 28495636
TI - Optimal experimental designs for fMRI when the model matrix is uncertain.
AB - This study concerns optimal designs for functional magnetic resonance imaging
(fMRI) experiments when the model matrix of the statistical model depends on both
the selected stimulus sequence (fMRI design), and the subject's uncertain
feedback (e.g. answer) to each mental stimulus (e.g. question) presented to
her/him. While practically important, this design issue is challenging. This
mainly is because that the information matrix cannot be fully determined at the
design stage, making it difficult to evaluate the quality of the selected
designs. To tackle this challenging issue, we propose an easy-to-use optimality
criterion for evaluating the quality of designs, and an efficient approach for
obtaining designs optimizing this criterion. Compared with a previously proposed
method, our approach requires a much less computing time to achieve designs with
high statistical efficiencies.
PMID- 28495634
TI - Network-targeted cerebellar transcranial magnetic stimulation improves
attentional control.
AB - Developing non-invasive brain stimulation interventions to improve attentional
control is extremely relevant to a variety of neurological and psychiatric
populations, yet few studies have identified reliable biomarkers that can be
readily modified to improve attentional control. One potential biomarker of
attention is functional connectivity in the core cortical network supporting
attention - the dorsal attention network (DAN). We used a network-targeted
cerebellar transcranial magnetic stimulation (TMS) procedure, intended to enhance
cortical functional connectivity in the DAN. Specifically, in healthy young
adults we administered intermittent theta burst TMS (iTBS) to the midline
cerebellar node of the DAN and, as a control, the right cerebellar node of the
default mode network (DMN). These cerebellar targets were localized using
individual resting-state fMRI scans. Participants completed assessments of both
sustained (gradual onset continuous performance task, gradCPT) and transient
attentional control (attentional blink) immediately before and after stimulation,
in two sessions (cerebellar DAN and DMN). Following cerebellar DAN stimulation,
participants had significantly fewer attentional lapses (lower commission error
rates) on the gradCPT. In contrast, stimulation to the cerebellar DMN did not
affect gradCPT performance. Further, in the DAN condition, individuals with worse
baseline gradCPT performance showed the greatest enhancement in gradCPT
performance. These results suggest that temporarily increasing functional
connectivity in the DAN via network-targeted cerebellar stimulation can enhance
sustained attention, particularly in those with poor baseline performance. With
regard to transient attention, TMS stimulation improved attentional blink
performance across both stimulation sites, suggesting increasing functional
connectivity in both networks can enhance this aspect of attention. These
findings have important implications for intervention applications of TMS and
theoretical models of functional connectivity.
PMID- 28495637
TI - Veridical stimulus localization is linked to human area V5/MT+ activity.
AB - How the brain represents visual space is an unsolved mystery. Spatial
localization becomes particularly challenging when visual information processing
is briefly disrupted, as in the case of saccadic eye movements, blinks, or visual
masks. As we have recently reported, a compression of visual space, illustrated
by displacements of shortly flashed stimuli, can be observed in the temporal
vicinity of masking stimuli during ocular fixation (Zimmermann et al., 2013). We
here aimed at investigating the neural mechanisms underlying these displacements
using functional magnetic resonance imaging. On the behavioral level, we detected
significant stimulus displacement when visual masks were simultaneously
presented. At the neural level, we observed decreased human motion complex V5/MT+
activation associated with these displacements: When comparing trials with a
perceived stimulus shift in space to trials of veridical perception of stimulus
localization, human V5/MT+ was significantly less activated although no
differences in perceived motion can account for this. Data suggest an important
role of human V5/MT+ in the process of spatial localization of briefly presented
objects and thus extend current concepts of the functions of human V5/MT+.
PMID- 28495638
TI - Targeting metabolism in pancreatic cancer.
PMID- 28495640
TI - Sources of Hematopoietic Stem and Progenitor Cells and Methods to Optimize Yields
for Clinical Cell Therapy.
AB - Bone marrow (BM) aspirates, mobilized peripheral blood, and umbilical cord blood
(UCB) have developed as graft sources for hematopoietic stem and progenitor cells
(HSPCs) for stem cell transplantation and other cellular therapeutics.
Individualized techniques are necessary to enhance graft HSPC yields and cell
quality from each graft source. BM aspirates yield adequate CD34+ cells but can
result in relative delays in engraftment. Granulocyte colony-stimulating factor
(G-CSF)-primed BM HSPCs may facilitate faster engraftment while minimizing graft
versus-host disease in certain patient subsets. The levels of circulating HSPCs
are enhanced using mobilizing agents, such as G-CSF and/or plerixafor, which act
via the stromal cell-derived factor 1/C-X-C chemokine receptor type 4 axis.
Alternate niche pathway mediators, including very late antigen-4/vascular cell
adhesion molecule-1, heparan sulfate proteoglycans, parathyroid hormone, and
coagulation cascade intermediates, may offer promising alternatives for graft
enhancement. UCB grafts have been expanded ex vivo with cytokines, notch-ligand,
or mesenchymal stromal cells, and most studies demonstrated greater quantities of
CD34+ cells ex vivo and improved short-term engraftment. No significant changes
were observed in long-term repopulating potential or in patient survival. Early
phase clinical trials using nicotinamide and StemReginin1 may offer improved
short- and long-term repopulating ability. Breakthroughs in genome editing and
stem cell reprogramming technologies may hasten the generation of pooled, third
party HSPC grafts. This review elucidates past, present, and potential future
approaches to HSPC graft optimization.
PMID- 28495639
TI - Safety and tolerability of the first-in-class agent CPI-613 in combination with
modified FOLFIRINOX in patients with metastatic pancreatic cancer: a single
centre, open-label, dose-escalation, phase 1 trial.
AB - BACKGROUND: Pancreatic cancer statistics are dismal, with a 5-year survival of
less than 10%, and more than 50% of patients presenting with metastatic disease.
Metabolic reprogramming is an emerging hallmark of pancreatic adenocarcinoma. CPI
613 is a novel anticancer agent that selectively targets the altered form of
mitochondrial energy metabolism in tumour cells, causing changes in mitochondrial
enzyme activities and redox status that lead to apoptosis, necrosis, and
autophagy of tumour cells. We aimed to establish the maximum tolerated dose of
CPI-613 when used in combination with modified FOLFIRINOX chemotherapy
(comprising oxaliplatin, leucovorin, irinotecan, and fluorouracil) in patients
with metastatic pancreatic cancer. METHODS: In this single-centre, open-label,
dose-escalation phase 1 trial, we recruited adult patients (aged >=18 years) with
newly diagnosed metastatic pancreatic adenocarcinoma from the Comprehensive
Cancer Center of Wake Forest Baptist Medical Center (Winston-Salem, NC, USA).
Patients had good bone marrow, liver and kidney function, and good performance
status (Eastern Cooperative Oncology Group [ECOG] performance status 0-1). We
studied CPI-613 in combination with modified FOLFIRINOX (oxaliplatin at 65 mg/m2,
leucovorin at 400 mg/m2, irinotecan at 140 mg/m2, and fluorouracil 400 mg/m2
bolus followed by 2400 mg/m2 over 46 h). We applied a two-stage dose-escalation
scheme (single patient and traditional 3+3 design). In the single-patient stage,
one patient was accrued per dose level. The starting dose of CPI-613 was 500
mg/m2 per day; the dose level was then escalated by doubling the previous dose if
there were no adverse events worse than grade 2 within 4 weeks attributed as
probably or definitely related to CPI-613. The traditional 3+3 dose-escalation
stage was triggered if toxic effects attributed as probably or definitely related
to CPI-613 were grade 2 or worse. The dose level for CPI-613 for the first cohort
in the traditional dose-escalation stage was the same as that used in the last
cohort of the single-patient dose-escalation stage. The primary objective was to
establish the maximum tolerated dose of CPI-613 (as assessed by dose-limiting
toxicities). This trial is registered with ClinicalTrials.gov, number
NCT01835041, and is closed to recruitment. FINDINGS: Between April 22, 2013, and
Jan 8, 2016, we enrolled 20 patients. The maximum tolerated dose of CPI-613 was
500 mg/m2. The median number of treatment cycles given at the maximum tolerated
dose was 11 (IQR 4-19). Median follow-up of the 18 patients treated at the
maximum tolerated dose was 378 days (IQR 250-602). Two patients enrolled at a
higher dose of 1000 mg/m2, and both had a dose-limiting toxicity. Two unexpected
serious adverse events occurred, both for the first patient enrolled. Expected
serious adverse events were: thrombocytopenia, anaemia, and lymphopenia (all for
patient number 2; anaemia and lymphopenia were dose-limiting toxicities);
hyperglycaemia (in patient number 7); hypokalaemia, hypoalbuminaemia, and sepsis
(patient number 11); and neutropenia (patient number 20). No deaths due to
adverse events were reported. For the 18 patients given the maximum tolerated
dose, the most common grade 3-4 non-haematological adverse events were
hyperglycaemia (ten [55%] patients), hypokalaemia (six [33%]), peripheral sensory
neuropathy (five [28%]), diarrhoea (five [28%]), and abdominal pain (four [22%]).
The most common grade 3-4 haematological adverse events were neutropenia (five
[28%] of 18 patients), lymphopenia (five [28%]), anaemia (four [22%], and
thrombocytopenia in three [17%]). Sensory neuropathy (all grade 1-3) was recorded
in 17 (94%) of the 18 patients and was managed with dose de-escalation or
discontinuation per standard of care. No patients died while on active treatment;
11 study participants died, with cause of death as terminal pancreatic cancer. Of
the 18 patients given the maximum tolerated dose, 11 (61%) achieved an objective
(complete or partial) response. INTERPRETATION: A maximum tolerated dose of CPI
613 was established at 500 mg/m2 when used in combination with modified
FOLFIRINOX in patients with metastatic pancreatic cancer. The findings of
clinical activity will require validation in a phase 2 trial. FUNDING:
Comprehensive Cancer Center of Wake Forest Baptist Medical Center.
PMID- 28495641
TI - Safety and Efficacy of Infliximab Therapy in the Setting of Steroid-Refractory
Acute Graft-versus-Host Disease.
AB - Acute graft-versus-host disease (aGVHD) is the leading cause of morbidity and
mortality after allogenic hematopoietic cell transplantation (HCT).
Corticosteroids are the first-line treatment; however, less than one-half of
patients achieve durable remission. Studies suggest that TNF-alpha, a cytokine
released from the bone marrow during conditioning, is involved in the
pathogenesis of aGVHD. We retrospectively evaluated the outcome of anti-TNF-alpha
therapy with infliximab in 35 patients with steroid refractory (SR) aGVHD.
Infliximab was administered intravenously at 10 mg/kg for a median of 4 doses
(range, 1 to 6) on a weekly basis. The overall response rates were 40% (17%
complete response [CR], 23% partial response [PR]) at 4 weeks, 23% (9% CR, 14%
PR) at 8 weeks, and 17% (all CR) at 12 weeks. Twenty-nine (83%) patients had
infectious complications within 12 weeks of initiation of infliximab. These
infections included 40 bacterial infections, 6 invasive fungal infections, and 5
viral reactivations. Twelve patients (34%) died secondary to infections. Overall
survival at 12 weeks and 6 months from the start of infliximab therapy was 37%
(13 of 35) and 17% (6 of 35), respectively; with most deaths secondary to
complications from GVHD and infections. In conclusion; the use of infliximab
therapy in patients with SR-aGVHD is associated with a modest poorly sustained
response along with a heightened risk of severe infections. Future studies with
more effective and less toxic therapies are needed for these patients.
PMID- 28495642
TI - Feasibility of Lenalidomide Therapy for Persistent Chronic Lymphocytic Leukemia
after Allogeneic Transplantation.
AB - In patients with chronic lymphocytic leukemia (CLL), persistence of disease after
allogeneic stem cell transplantation (alloSCT) can result in poor outcomes. In an
effort to improve these outcomes, patients with persistent CLL who were 90 to 100
days beyond alloSCT with no evidence of graft-versus-host-disease (GVHD) were
randomized to receive lenalidomide or standard care (withdrawal of
immunosuppression followed by donor lymphocyte infusion). Lenalidomide was
initiated at 5 mg every other day and increased to 10 mg daily, if tolerated, in
each patient. Of 38 patients enrolled, 17 (45%) met the eligibility criteria for
randomization. Of these 17 patients, 8 were randomized to undergo lenalidomide
therapy. Five (62%) patients had to stop taking the drug because of toxicity. The
main reason for drug discontinuation was acute GVHD in 43% of patients. This
incidence was 11% in the patients who were randomized to not receive
lenalidomide. With a median follow-up of 2.6 years, the median survival was 3.4
years for those receiving lenalidomide. This was not reached in patients
randomized to not receive lenalidomide and in patients in complete remission who
were not randomized. These results suggested that treatments other than
lenalidomide are needed for persistent CLL after alloSCT.
PMID- 28495643
TI - Humoral Immune Reconstitution Kinetics after Allogeneic Hematopoietic Stem Cell
Transplantation in Children: A Maturation Block of IgM Memory B Cells May Lead to
Impaired Antibody Immune Reconstitution.
AB - Although T cell immune reconstitution after allogeneic hematopoietic stem cell
transplantation (allo-HSCT) has been well studied, long-term B cell immune
reconstitution remains less characterized. We evaluated humoral immune
reconstitution among 71 pediatric allo-HSCT recipients. Although tetanus toxoid
antibody levels were normal at 1 year after allo-HSCT, antipolysaccharide
carbohydrate antibodies remained persistently low for up to 5 years. While naive
B cell counts normalized by 6 months, IgM memory B cell deficiency persisted for
up to 2 years (P = .01); switched memory B cell deficiency normalized by 1 year
after allo-HSCT. CD4+ T cell immune reconstitution correlated with that of
switched memory B cells as early as 6 months after allo-HSCT (r = .55, P = .002)
but did not correlate with IgM memory B cells at any time point after allo-HSCT.
Taken together, this suggests that allo-HSCT recipients have impaired antibody
immune reconstitution, mainly due to IgM memory B cell maturation block, compared
with more prompt T cell-dependent switched memory cell immune reconstitution. We
further explored other factors that might affect humoral immune reconstitution.
The use of total body irradiation was associated with lower naive B cells counts
at 6 months after HSCT (P = .04) and lower IgM (P = .008) and switched (P = .003)
memory B cells up to 2 years. Allo-HSCT recipients with extensive chronic graft
versus-host disease had lower IgM memory B cell counts (P = .03) up to 2 years
after allo-HSCT. The use of cord blood was associated with better naive (P =
.01), IgM (P = .0005), and switched memory (P = .006) B cells immune
reconstitution. These findings may inform future prophylaxis and treatment
strategies regarding risk of overwhelming infection, graft-versus-host disease,
and post-allogeneic HSCT revaccination.
PMID- 28495644
TI - Improving core outcome set development: qualitative interviews with developers
provided pointers to inform guidance.
AB - OBJECTIVES: The objective of the study was to explore core outcome set (COS)
developers' experiences of their work to inform methodological guidance on COS
development and identify areas for future methodological research. STUDY DESIGN
AND SETTING: Semistructured, audio-recorded interviews with a purposive sample of
32 COS developers. Analysis of transcribed interviews was informed by the
constant comparative method and framework analysis. RESULTS: Developers found COS
development to be challenging, particularly in relation to patient participation
and accessing funding. Their accounts raised fundamental questions about the
status of COS development and whether it is consultation or research. Developers
emphasized how the absence of guidance had affected their work and identified
areas where guidance or evidence about COS development would be useful including,
patient participation, ethics, international development, and implementation.
They particularly wanted guidance on systematic reviews, Delphi, and consensus
meetings. CONCLUSION: The findings raise important questions about the funding,
status, and process of COS development and indicate ways that it could be
strengthened. Guidance could help developers to strengthen their work, but over
specification could threaten quality in COS development. Guidance should
therefore highlight common issues to consider and encourage tailoring of COS
development to the context and circumstances of particular COS.
PMID- 28495645
TI - Inflammatory pseudotumour of the infratemporal fossa visualized with 18F-FDG
PET/CT.
AB - The inflammatory pseudotumour of the head and neck is a benign lesion, extremely
rare outside the cranial orbits. A case is presented of an inflammatory
pseudotumour not associated with the IgG4-related disease. The pseudotumour was
found as a solitary mass in the infratemporal fossa of a young woman who
complained of otalgia and hearing loss. A clear image of the lesion was obtained
using an 18F-fluoro-deoxy-glucose (18F-FDG) PET. After the histopathological
diagnosis, and treatment with corticosteroids, a second 18F-FDG PET was
performed. The metabolic image had returned to normal, and the previously
observed mass disappeared. A brief review is presented of the studies examining
this type of lesion.
PMID- 28495646
TI - 18F-FDG PET/CT in the detection of a primary radiation-induced metastatic
angiosarcoma.
PMID- 28495647
TI - Prevalence of human cosavirus and saffold virus with an emergence of saffold
virus genotype 6 in patients hospitalized with acute gastroenteritis in Chiang
Mai, Thailand, 2014-2016.
AB - Human cosavirus and saffold virus are both newly discovered members of the
Picornaviridae family. It has been suggested that these viruses may be the
causative agents of acute gastroenteritis. In this study, 1093 stool samples
collected from patients with acute gastroenteritis between January 2014 and
December 2016, were screened for cosavirus and saffold virus using reverse
transcription-polymerase chain reaction. The viral genotypes were then
established via nucleotide sequencing. Here, cosavirus was detected in 16 of 1093
stool samples (1.5%) and saffold virus was detected in 18 of 1093 stool samples
(1.6%). The saffold virus genotypes 1 (16.7%), 2 (50%) and 6 (33.3%), and the
cosavirus genetic groups A (87.5%), C (6.25%) and D (6.25%), were all identified
across the three-year study period. Interestingly, saffold virus genotype 6 has
now been detected for the first time in Thailand. The present study provides the
prevalence of cosavirus and saffold virus with the emergence of saffold virus
genotype 6 in Thailand.
PMID- 28495648
TI - Complete genome sequences of two avian infectious bronchitis viruses isolated in
Egypt: Evidence for genetic drift and genetic recombination in the circulating
viruses.
AB - Avian infectious bronchitis virus (IBV) is highly prevalent in chicken
populations and is responsible for severe economic losses to poultry industry
worldwide. In this study, we report the complete genome sequences of two IBV
field strains, CU/1/2014 and CU/4/2014, isolated from vaccinated chickens in
Egypt in 2014. The genome lengths of the strains CU/1/2014 and CU/4/2014 were
27,615 and 27,637 nucleotides, respectively. Both strains have a common genome
organization in the order of 5'-UTR-1a-1b-S-3a-3b-E-M-4b-4c-5a-5b-N-6b-UTR
poly(A) tail-3'. Interestingly, strain CU/1/2014 showed a novel 15-nt deletion in
the 4b-4c gene junction region. Phylogenetic analysis of the full S1 genes showed
that the strains CU/1/2014 and CU/4/2014 belonged to IBV genotypes GI-1 lineage
and GI-23 lineage, respectively. The genome of strain CU/1/2014 is closely
related to vaccine strain H120 but showed genome-wide point mutations that lead
to 27, 14, 11, 1, 1, 2, 2, and 2 amino acid differences between the two strains
in 1a, 1b, S, 3a, M, 4b, 4c, and N proteins, respectively, suggesting that strain
CU/1/2014 is probably a revertant of the vaccine strain H120 and evolved by
accumulation of point mutations. Recombination analysis of strain CU/4/2014
showed evidence for recombination from at least three different IBV strains,
namely, the Italian strain 90254/2005 (QX-like strain), 4/91, and H120. These
results indicate the continuing evolution of IBV field strains by genetic drift
and by genetic recombination leading to outbreaks in the vaccinated chicken
populations in Egypt.
PMID- 28495649
TI - Identification and molecular characterization of novel primate bocaparvoviruses
from wild western lowland gorillas of Moukalaba-Doudou National Park, Gabon.
AB - Bocaparvoviruses have been studied extensively owing to their ability to cause
respiratory illness or gastroenteritis in humans. Some bocaparvoviruses have been
detected in non-human primates (gorillas and chimpanzees), but the diversity and
evolution of these viruses are not fully understood. In this study, we collected
107 fecal samples from wild western lowland gorillas in Moukalaba-Doudou National
Park in Gabon to investigate the presence of bocaparvoviruses. Using a
combination of pan-bocaparvovirus PCR and individual identification by
microsatellite genotyping, we found that two samples from two apparently healthy
infant gorillas were positive for bocaparvovirus. Sequencing and phylogenetic
analyses revealed that the two gorilla bocaparvovirus strains are nearly
identical and are closely related to viruses in the species Primate
bocaparvovirus 2 (with 86.0% nucleotide identity to a human bocavirus 2 isolate).
To our knowledge, this is the first report showing the presence of a non-human
primate bocaparovirus within Primate bocaparvovirus 2. Our findings provide novel
insights into the diversity and evolution of bocaparvoviruses and highlight the
importance of surveying these viruses for the safe management of gorilla-based
ecotourism.
PMID- 28495650
TI - Extent of coronary artery disease in patients undergoing angiography for stable
or acute coronary syndromes.
AB - BACKGROUND: We aimed to investigate whether the angiographic extent of coronary
artery disease (CAD) differs in patients undergoing coronary angiography for
stable CAD or acute coronary syndrome (ACS) and identify predictors of CAD extent
in these patients. METHODS: We enrolled 584 consecutive patients (463 with stable
CAD, 121 with ACS) with angiographically established CAD (>=1 stenosis >25%). The
Gensini score was used to assess the extent of coronary atherosclerosis. RESULTS:
Stable CAD patients had greater Framingham risk score and greater prevalence of
hypertension, hypercholesterolemia, and diabetes (p<0.05 for all). Fasting
glucose and systolic and diastolic blood pressure were higher, while high
sensitivity C-reactive protein (hsCRP) levels were lower in patients with stable
CAD than in those with ACS (p<0.05 for all). No difference in Gensini score was
observed between the two groups (p=0.118), but patients with ACS were more likely
to have at least one significant epicardial angiographic lesion (>50% stenosis)
(OR 2.0, p=0.022). Higher Gensini score was independently associated with (i)
higher hsCRP and glucose levels, hypercholesterolemia, and increased age in
stable CAD patients (R2 0.15, p<0001) and (ii) increased age and higher glucose
and hsCRP levels in patients with ACS (R2 0.17, p<0001). CONCLUSIONS: Patients
undergoing coronary angiography for ACS or stable CAD presented with a similar
extent of angiographic CAD, although patients with ACS had a higher prevalence of
significant lesions in the presence of a better cardiovascular risk profile and
higher inflammation levels. The extent of angiographic CAD in both the groups
shared common determinants such as hsCRP, age, and hyperglycemia, but these
appeared to explain only a small part of the variation of coronary
atherosclerosis.
PMID- 28495651
TI - Percentile categorization of QT interval as an approach for identifying adult
patients at risk for cardiovascular death.
AB - BACKGROUND: The results from studies of the association of QT prolongation with
cardiovascular death (CVD) have been inconsistent. OBJECTIVE: The purpose of this
study was to compare the major correction formulas to percentile values of QT for
heart rate ranges as to their ability to remove the relationship of QT to heart
rate and to predict CVD. METHODS: Participants were 16,531 veterans who had an
initial ECG at the Veterans Affairs Medical Center, Palo Alto, between March 31,
1987, and December 20, 1999, and were followed for CVD. The 4 major correction
formulas (Bazett, Fridericia, Framingham, and Hodges) were used to correct QT
interval. In addition, the percentiles for heart rate ranges as proposed by
Schwartz were calculated. RESULTS: During median follow-up of 17.8 years, 455 CVD
events occurred. When compared to the other equations, QTc Bazett had the
greatest dependence on heart rate (R2 = 0.18). The hazard ratio (95% confidence
interval) for CVD was 2.08 (1.28-3.9) for the 98th percentile of QT interval by
heart rate ranges, 2.05 (1.27-3.33) for QTc Bazett, 1.39 (0.44-4.34) for QTc
Fridericia, 1.05 (0.26-4.24) for QTc Hodges, and 1.12 (0.28-4.52) for QTc
Framingham. The hazard ratio of QTc Bazett was significantly higher than the
other formulas except for the 98th percentile method. CONCLUSION: The Framingham,
Hodges, and Fridericia equations remove the effect of heart rate on QT interval
significantly better than the Bazett equation. Using QT-interval percentiles
based on heart rate provides a consistent approach both for identifying those
whose QT intervals prolong due to drugs or other stressors and for assessing CVD
risk.
PMID- 28495653
TI - In search of the holy grail in the channelopathy field: Proving pathogenicity of
long QT syndrome-associated variants?
PMID- 28495652
TI - Acute efficacy, safety, and long-term clinical outcomes using the second
generation cryoballoon for pulmonary vein isolation in patients with a left
common pulmonary vein: A multicenter study.
AB - BACKGROUND: Second-generation cryoballoon (CB2)-based pulmonary vein isolation
(PVI) has demonstrated encouraging clinical results in the treatment of
paroxysmal (PAF) and persistent atrial fibrillation (PersAF). However, the CB2
features a maximal diameter of 28 mm, and its adaptability to anatomic variations
of the pulmonary veins (PVs) might be challenging. OBJECTIVE: The purpose of this
study was to assess the acute efficacy, safety, and long-term clinical results of
CB2-based PVI in patients with a left common pulmonary vein (LCPV). METHODS: Six
hundred seventy consecutive patients underwent CB2-based PVI in 3
electrophysiology centers. In 74 patients (11%), an LCPV was identified (LCPV
group). The data were compared to those from matched patients (n = 74) with
normal PV anatomy and comparable baseline characteristics (control group). An
antral occlusion of the complete LCPV ostium was feasible in 50% of patients in
the LCPV group. If an antral occlusion could not be obtained, a sequential
isolation of the first superior and inferior branches was applied. RESULTS: All
74 LCPVs were successfully isolated. A total of 64% patients (LCPV group) and 66%
patients (control group) remained in sinus rhythm after mean follow-up of 1.9 +/-
0.9 years (P = .820). In 18 of 26 patients (69%) with atrial tachyarrhythmia
recurrence, a repeat procedure using radiofrequency energy was performed, and a
total of 56% LCPVs were found to be persistently isolated (control group: 61% of
left-sided PVs, P = .801). CONCLUSION: Patients with an LCPV undergoing CB2-based
PVI demonstrate a high acute success rate. Comparable results with regard to
clinical success and durability of PVI were shown when comparing patients of the
LCPV group and the control group.
PMID- 28495654
TI - Minimally invasive surgical ablation: Should we ablate harder or smarter?
PMID- 28495655
TI - Increased sodium/calcium exchanger activity enhances beta-adrenergic-mediated
increase in heart rate: Whole-heart study in a homozygous sodium/calcium
exchanger overexpressor mouse model.
AB - BACKGROUND: The cardiac sodium/calcium (Na+/Ca2+) exchanger (NCX) contributes to
diastolic depolarization in cardiac pacemaker cells. Increased NCX activity has
been found in heart failure and atrial fibrillation. The influence of increased
NCX activity on resting heart rate, beta-adrenergic-mediated increase in heart
rate, and cardiac conduction properties is unknown. OBJECTIVE: The purpose of
this study was to investigate the influence of NCX overexpression in a homozygous
transgenic whole-heart mouse model (NCX-OE) on sinus and AV nodal function.
METHODS: Langendorff-perfused, beating whole hearts of NCX-OE and the
corresponding wild-type (WT) were studied +/- isoproterenol (ISO; 0.2 MUM).
Epicardial ECG, AV nodal Wenckebach cycle length (AVN-WCL), and retrograde AVN
WCL were obtained. RESULTS: At baseline, basal heart rate was unaltered between
NCX-OE and WT (WT: cycle length [CL] 177.6 +/- 40.0 ms, no. of hearts [n] = 20;
NCX-OE: CL 185.9 +/- 30.5 ms, n = 18; P = .21). In the presence of ISO, NCX-OE
exhibited a significantly higher heart rate compared to WT (WT: CL 133.4 +/- 13.4
ms, n = 20; NCX-OE: CL 117.7 +/- 14.2 ms, n = 18; P <.001). ISO led to a
significant shortening of the anterograde and retrograde AVN-WCL without
differences between NCX-OE and WT. CONCLUSION: This study is the first to
demonstrate that increased NCX activity enhances beta-adrenergic increase of
heart rate. Mechanistically, increased NCX inward mode activity may promote
acceleration of diastolic depolarization in sinus nodal pacemaker cells, thus
enhancing chronotropy in NCX-OE. These findings suggest a novel potential
therapeutic target for heart rate control in the presence of increased NCX
activity, such as heart failure.
PMID- 28495656
TI - Dehydroepiandrosterone sulfate augments blood-brain barrier and tight junction
protein expression in brain endothelial cells.
AB - Tight junctions (TJ) between brain endothelial cells are essential for formation
and maintenance of the blood-brain barrier (BBB). Although loss of BBB integrity
is associated with several neuropathological disorders, treatments that augment
or stabilise the BBB are scarce. Here we show that physiological concentrations
of dehydroepiandrosterone sulfate (DHEAS) stimulate the expression of the TJ
proteins zonula occludens-1 (ZO-1) and claudin-3 in the brain-derived endothelial
cell line bEnd.3 and promote TJ formation between neighbouring cells,
demonstrated by augmented transendothelial resistance across cell monolayers.
Silencing androgen receptor expression by siRNA does not prevent DHEAS-induced
stimulation of ZO-1 expression, indicating that conversion of DHEAS into
testosterone is not required for its actions. Suppression of Gnalpha11 expression
by siRNA prevents DHEAS actions, pointing towards a G-protein-coupled receptor as
being a mediator of the DHEAS effects. These results are consistent with the idea
that DHEAS, acting as a hormone in its own right, supports the integrity of the
BBB. The current findings might help in developing new strategies for the
prevention or treatment of neurological disorders associated with BBB defects.
PMID- 28495657
TI - Outer membrane vesicles extracted from Neisseria meningitidis serogroup X for
prevention of meningococcal disease in Africa.
AB - Meningococcal disease is caused mainly by serogroups A, B, C, Y, W of N.
meningitidis. However, numerous cases of meningitis caused by serogroup X N.
meningitidis (MenX) have recently been reported in several African countries.
Currently, there are no licensed vaccines against this pathogen and most of the
MenX cases have been caused by meningococci from clonal complex (c.c) 181.
Detergent extracted meningococcal outer membrane vesicle (dOMV) vaccines have
previously shown to be safe and effective against epidemics of serogroup B
meningococcal disease in all age groups. The aim of this work is therefore to
obtain, characterize and evaluate the vaccine potential of dOMVs derived from a
MenX strain (OMVx). Three experimental lots of OMVx were prepared by deoxycholate
extraction from the MenX strain BF 2/97. Size and morphology of the vesicles was
determined by Dynamic Light Scattering and electron microscopy, whereas the
antigenic composition was characterized by gel electrophoresis and
immunoblotting. OMVx were thereafter adsorbed to aluminium hydroxide (OMVx/AL)
and two doses of OMVx were administered s.c. to groups of Balb/c mice three weeks
apart. The immunogenicity and functional antibody activities in sera were
evaluated by ELISA (anti-OMVx specific IgG responses) and serum bactericidal
activity (SBA) assay. The size range of OMVx was shown to be between 90 and
120nm, whereas some of the antigens detected were the outer membrane proteins
PorA, OpcA and RmpM. The OMVx/AL elicited high anti-OMVx antibody responses with
bactericidal activity and no bactericidal activity was observed in the control
group of no immunised mice. The results demonstrate that OMVx are immunogenic and
could form part of a future vaccine to prevent the majority of meningococcal
disease in the African meningitis belt.
PMID- 28495658
TI - Genomics of hypertension.
AB - A complex network of interacting pathways involving renal, neural, endocrine,
vascular and other mechanisms controls the main determinants of blood pressure -
cardiac output and total peripheral resistance. Multiple genes within each of
these systems contribute to the specialized functions regulating blood pressure.
The monogenic forms of blood pressure dysregulation have provided valuable
insights into blood pressure regulation and expanded our understanding of both
the mechanisms and the treatment of hypertension. Genome wide association studies
have identified over 100 single nucleotide polymorphisms associated with blood
pressure phenotypes and have identified plausible novel pathways of BP regulation
and putative drug targets.
PMID- 28495659
TI - Social inclusion of individuals with intellectual disabilities in the military.
AB - BACKGROUND: Despite policies advocating the social inclusion of persons with
disabilities in all settings that are a part of everyday life within society,
individuals with intellectual disabilities (ID) are usually excluded from service
in the military. AIMS: This study examined the meaning of service in the military
for individuals with ID from the perspective of various stakeholder groups.
METHODS AND PROCEDURES: Semi-structured qualitative interviews were conducted
with 31 individuals with ID, 36 relatives, and 28 commanders. The recent model
for social inclusion developed by Simplican et al. (2015) served as the basis for
analyses. OUTCOMES AND RESULTS: Findings suggest a successful social inclusion
process for individuals with ID, which resulted in them feeling as an integral
part and as contributing members of the military unit and of society at large.
Social inclusion in the military was described with reference to two overlapping
and interacting domains of interpersonal relationships and community
participation. CONCLUSIONS AND IMPLICATIONS: The interaction between
interpersonal relationships within the military and community participation has
led to positive outcomes for soldiers with ID. Recommendations are provided for
the continued inclusion of individuals with ID in the military and in other
everyday settings.
PMID- 28495660
TI - Geriatric Patient Safety Indicators Based on Linked Administrative Health Data to
Assess Anticoagulant-Related Thromboembolic and Hemorrhagic Adverse Events in
Older Inpatients: A Study Proposal.
AB - BACKGROUND: Frail older people with multiple interacting conditions,
polypharmacy, and complex care needs are particularly exposed to health care
related adverse events. Among these, anticoagulant-related thromboembolic and
hemorrhagic events are particularly frequent and serious in older inpatients. The
growing use of anticoagulants in this population and their substantial risk of
toxicity and inefficacy have therefore become an important patient safety and
public health concern worldwide. Anticoagulant-related adverse events and the
quality of anticoagulation management should thus be routinely assessed to
improve patient safety in vulnerable older inpatients. OBJECTIVE: This project
aims to develop and validate a set of outcome and process indicators based on
linked administrative health data (ie, insurance claims data linked to hospital
discharge data) assessing older inpatient safety related to anticoagulation in
both Switzerland and France, and enabling comparisons across time and among
hospitals, health territories, and countries. Geriatric patient safety indicators
(GPSIs) will assess anticoagulant-related adverse events. Geriatric quality
indicators (GQIs) will evaluate the management of anticoagulants for the
prevention and treatment of arterial or venous thromboembolism in older
inpatients. METHODS: GPSIs will measure cumulative incidences of thromboembolic
and bleeding adverse events based on hospital discharge data linked to insurance
claims data. Using linked administrative health data will improve GPSI risk
adjustment on patients' conditions that are present at admission and will capture
in-hospital and postdischarge adverse events. GQIs will estimate the proportion
of index hospital stays resulting in recommended anticoagulation at discharge and
up to various time frames based on the same electronic health data. The GPSI and
GQI development and validation process will comprise 6 stages: (1) selection and
specification of candidate indicators, (2) definition of administrative data
based algorithms, (3) empirical measurement of indicators using linked
administrative health data, (4) validation of indicators, (5) analyses of
geographic and temporal variations for reliable and valid indicators, and (6)
data visualization. RESULTS: Study populations will consist of 166,670 Swiss and
5,902,037 French residents aged 65 years and older admitted to an acute care
hospital at least once during the 2012-2014 period and insured for at least 1
year before admission and 1 year after discharge. We will extract Swiss data from
the Helsana Group data warehouse and French data from the national health
insurance information system (SNIIR-AM). The study has been approved by Swiss and
French ethics committees and regulatory organizations for data protection.
CONCLUSIONS: Validated GPSIs and GQIs should help support and drive quality and
safety improvement in older inpatients, inform health care stakeholders, and
enable international comparisons. We discuss several limitations relating to the
representativeness of study populations, accuracy of administrative health data,
methods used for GPSI criterion validity assessment, and potential confounding
bias in comparisons based on GQIs, and we address these limitations to strengthen
study feasibility and validity.
PMID- 28495661
TI - Virtual Reality as an Adjunct Home Therapy in Chronic Pain Management: An
Exploratory Study.
AB - BACKGROUND: Virtual reality (VR) therapy has been successfully used as an adjunct
therapy for the management of acute pain in adults and children, and evidence of
potential efficacy in other health applications is growing. However, minimal
research exists on the value of VR as an intervention for chronic pain.
OBJECTIVE: This case series examined the value of VR to be used as an adjunctive
therapy for chronic pain patients in their own homes. METHODS: An exploratory
approach using a case series and personal interviews was used. Ten chronic pain
patients received VR therapy for 30 min on alternate days for 1 month. Pre- and
postexposure (immediately afterwards, 3 h, and at 24 h) pain assessment was
recorded using the Numerical Rating Scale (NRS), and weekly using the Brief Pain
Inventory (BPI) and Self-completed Leeds Assessment of Neuropathic Symptoms and
Signs pain scale (S-LANSS). Terminal semistructured personal interviews with the
patients were also undertaken. RESULTS: Of the 8 patients who completed the
study, 5 of them reported that pain was reduced during the VR experience but no
overall treatment difference in pain scores postexposure was observed. VR was not
associated with any serious adverse events, although 60% of patients reported
some cybersickness during some of the experiences. CONCLUSIONS: Of note is that
the majority of these study participants reported a reduction in pain while using
the VR but with highly individualized responses. One patient also reported some
short-term improved mobility following VR use. Some evidence was found for the
short-term efficacy of VR in chronic pain but no evidence for persistent
benefits.
PMID- 28495663
TI - Brexit is bad for health, and doctors should say so.
PMID- 28495664
TI - What do NHS doctors think about their work?
PMID- 28495662
TI - The Development, Validation, and User Evaluation of Foodbook24: A Web-Based
Dietary Assessment Tool Developed for the Irish Adult Population.
AB - BACKGROUND: The application of technology in the area of dietary assessment has
resulted in the development of an array of tools, which are often specifically
designed for a particular country or region. OBJECTIVE: The aim of this study was
to describe the development, validation, and user evaluation of a Web-based
dietary assessment tool "Foodbook24." METHODS: Foodbook24 is a Web-based, dietary
assessment tool consisting of a 24-hour dietary recall (24HDR) and food frequency
questionnaire (FFQ) alongside supplementary questionnaires. Validity of the 24HDR
component was assessed by 40 participants, who completed 3 nonconsecutive, self
administered 24HDR using Foodbook24 and a 4-day semi-weighed food diary at
separate time points. Participants also provided fasted blood samples and 24-hour
urine collections for the identification of biomarkers of nutrient and food group
intake during each recording period. Statistical analyses on the nutrient and
food group intake data derived from each method were performed in SPSS version
20.0 (SPSS Inc). Mean nutrient intakes (and standard deviations) recorded using
each method of dietary assessment were calculated. Spearman and Pearson
correlations, Wilcoxon Signed Rank and Paired t test were used to investigate the
agreement and differences between the nutritional output from Foodbook24 (test
method) and the 4-day semi-weighed food diary (reference method). Urinary and
plasma biomarkers of nutrient intake were used as an objective validation of
Foodbook24. To investigate the user acceptability of Foodbook24, participants
from different studies involved with Foodbook24 were asked to complete an
evaluation questionnaire. RESULTS: For nutrient intake, correlations between the
dietary assessment methods were acceptable to very good in strength and
statistically significant (range r=.32 to .75). There were some significant
differences between reported mean intakes of micronutrients recorded by both
methods; however, with the exception of protein (P=.03), there were no
significant differences in the reporting of energy or macronutrient intake. Of
the 19 food groups investigated in this analysis, there were significant
differences between 6 food groups reported by both methods. Spearman correlations
for biomarkers of nutrient and food group intake and reported intake were similar
for both methods. A total of 118 participants evaluated the acceptability of
Foodbook24. The tool was well-received and the majority, 67.8% (80/118), opted
for Foodbook24 as the preferred method for future dietary intake assessment when
compared against a traditional interviewer led recall and semi-weighed food
diary. CONCLUSIONS: The results of this study demonstrate the validity and user
acceptability of Foodbook24. The results also highlight the potential of
Foodbook24, a Web-based dietary assessment method, and present a viable
alternative to nutritional surveillance in Ireland.
PMID- 28495665
TI - General anaesthesia under the age of 4 years has minimal impact on future
academic performance.
PMID- 28495666
TI - How to use nasal nitric oxide in a child with suspected primary ciliary
dyskinesia.
AB - Measuring nasal nitric oxide (nNO) is increasingly used as part of testing for
primary ciliary dyskinesia (PCD). The diagnosis of PCD is often delayed until
after bronchiectasis is established and auditory damage has occurred. It is
important that all paediatricians are aware of clinical features that are
suggestive of PCD that should prompt diagnostic testing. nNO levels are
recognised to be low in people with PCD and results generated by static
chemiluminescence analysers using velum closure technique in older children have
good sensitivity and specificity. However, to conclusively rule PCD in or out,
further tests of ciliary function are required and assessment of cilia
ultrastructure, immunohistochemistry studies and genotyping may also be
indicated. These tests are more complex, invasive and expensive than nNO. nNO is
less well studied in younger children where tidal breathing measurements are
required. Portable nitric oxide analysers are also increasingly used in practice.
This paper discusses when to consider PCD as a possible diagnosis in a child
along with the indications, physiological and technical background and clinical
utility of nNO as a test for PCD in children.
PMID- 28495667
TI - Fifteen-minute consultation in the normal child: Challenges relating to sexuality
and gender identity in children and young people.
AB - Lesbian, gay, bisexual and transgender (LGBT+) young people face several
challenges in their daily lives, including specific healthcare inequalities.
Negative societal attitudes towards sexual and gender minorities, and the effects
of regular experiences of bullying and homophobia/transphobia exacerbate the
normal trials and tribulations of childhood and adolescence. Barriers to
accessing healthy activities, such as sport, are created by perceived stigma and
real-life experiences. Healthcare environments are by default heteronormative and
contribute to the isolation and exclusion of LGBT+ young people. Paediatricians
are well placed to act on these healthcare inequalities and to advocate for LGBT+
youth, through simple changes to individual practice as well as system-wide
improvements.
PMID- 28495668
TI - Price cap could mean patients miss out on newest stents, cardiologists warn.
PMID- 28495670
TI - Do rapid diagnostic tests improve overall quality of care?
PMID- 28495671
TI - Waiting times at their "worst," but quality of care holds up.
PMID- 28495672
TI - Elevated serum levels of sonic hedgehog are associated with fibrotic and vascular
manifestations in systemic sclerosis.
PMID- 28495673
TI - Parallel imaging of Drosophila embryos for quantitative analysis of genetic
perturbations of the Ras pathway.
AB - The Ras pathway patterns the poles of the Drosophila embryo by downregulating the
levels and activity of a DNA-binding transcriptional repressor Capicua (Cic). We
demonstrate that the spatiotemporal pattern of Cic during this signaling event
can be harnessed for functional studies of mutations in the Ras pathway in human
diseases. Our approach relies on a new microfluidic device that enables parallel
imaging of Cic dynamics in dozens of live embryos. We found that although the
pattern of Cic in early embryos is complex, it can be accurately approximated by
a product of one spatial profile and one time-dependent amplitude. Analysis of
these functions of space and time alone reveals the differential effects of
mutations within the Ras pathway. Given the highly conserved nature of Ras
dependent control of Cic, our approach provides new opportunities for functional
analysis of multiple sequence variants from developmental abnormalities and
cancers.
PMID- 28495674
TI - Noncentral Nervous System Systemic Embolism in Patients With Atrial Fibrillation:
Results From ROCKET AF (Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition
Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in
Atrial Fibrillation).
PMID- 28495675
TI - High-Value Home Health Care for Patients With Heart Failure: An Opportunity to
Optimize Transitions From Hospital to Home.
PMID- 28495676
TI - The Review and Editorial Process at Circulation: Cardiovascular Quality and
Outcomes: The Worst System, Except for All the Others.
PMID- 28495677
TI - High-throughput and site-specific identification of 2'-O-methylation sites using
ribose oxidation sequencing (RibOxi-seq).
AB - Ribose methylation (2'-O-methylation, 2'-OMe) occurs at high frequencies in rRNAs
and other small RNAs and is carried out using a shared mechanism across
eukaryotes and archaea. As RNA modifications are important for ribosome
maturation, and alterations in these modifications are associated with cellular
defects and diseases, it is important to characterize the landscape of 2'-O
methylation. Here we report the development of a highly sensitive and accurate
method for ribose methylation detection using next-generation sequencing. A key
feature of this method is the generation of RNA fragments with random 3'-ends,
followed by periodate oxidation of all molecules terminating in 2',3'-OH groups.
This allows only RNAs harboring 2'-OMe groups at their 3'-ends to be sequenced.
Although currently requiring microgram amounts of starting material, this method
is robust for the analysis of rRNAs even at low sequencing depth.
PMID- 28495678
TI - Sphingolipid metabolic flow controls phosphoinositide turnover at the trans-Golgi
network.
AB - Sphingolipids are membrane lipids globally required for eukaryotic life. The
sphingolipid content varies among endomembranes with pre- and post-Golgi
compartments being poor and rich in sphingolipids, respectively. Due to this
different sphingolipid content, pre- and post-Golgi membranes serve different
cellular functions. The basis for maintaining distinct subcellular sphingolipid
levels in the presence of membrane trafficking and metabolic fluxes is only
partially understood. Here, we describe a homeostatic regulatory circuit that
controls sphingolipid levels at the trans-Golgi network (TGN). Specifically, we
show that sphingomyelin production at the TGN triggers a signalling pathway
leading to PtdIns(4)P dephosphorylation. Since PtdIns(4)P is required for
cholesterol and sphingolipid transport to the trans-Golgi network, PtdIns(4)P
consumption interrupts this transport in response to excessive sphingomyelin
production. Based on this evidence, we envisage a model where this homeostatic
circuit maintains a constant lipid composition in the trans-Golgi network and
post-Golgi compartments, thus counteracting fluctuations in the sphingolipid
biosynthetic flow.
PMID- 28495679
TI - Autophagosome formation is initiated at phosphatidylinositol synthase-enriched ER
subdomains.
AB - The autophagosome, a double-membrane structure mediating degradation of
cytoplasmic materials by macroautophagy, is formed in close proximity to the
endoplasmic reticulum (ER). However, how the ER membrane is involved in autophagy
initiation and to which membrane structures the autophagy-initiation complex is
localized have not been fully characterized. Here, we were able to biochemically
analyze autophagic intermediate membranes and show that the autophagy-initiation
complex containing ULK and FIP200 first associates with the ER membrane. To
further characterize the ER subdomain, we screened phospholipid biosynthetic
enzymes and found that the autophagy-initiation complex localizes to
phosphatidylinositol synthase (PIS)-enriched ER subdomains. Then, the initiation
complex translocates to the ATG9A-positive autophagosome precursors in a PI3P
dependent manner. Depletion of phosphatidylinositol (PI) by targeting bacterial
PI-specific phospholipase C to the PIS domain impairs recruitment of downstream
autophagy factors and autophagosome formation. These findings suggest that the
autophagy-initiation complex, the PIS-enriched ER subdomain, and ATG9A vesicles
together initiate autophagosome formation.
PMID- 28495680
TI - DNA-binding determinants and cellular thresholds for human telomerase repeat
addition processivity.
AB - The reverse transcriptase telomerase adds telomeric repeats to chromosome ends.
Purified human telomerase catalyzes processive repeat synthesis, which could
restore the full ~100 nucleotides of (T2AG3)n lost from replicated chromosome
ends as a single elongation event. Processivity inhibition is proposed to be a
basis of human disease, but the impacts of different levels of processivity on
telomere maintenance have not been examined. Here, we delineate side chains in
the telomerase active-site cavity important for repeat addition processivity,
determine how they contribute to duplex and single-stranded DNA handling, and
test the cellular consequences of partial or complete loss of repeat addition
processivity for telomere maintenance. Biochemical findings oblige a new model
for DNA and RNA handling dynamics in processive repeat synthesis. Biological
analyses implicate repeat addition processivity as essential for telomerase
function. However, telomeres can be maintained by telomerases with lower than
wild-type processivity. Furthermore, telomerases with low processivity
dramatically elongate telomeres when overexpressed. These studies reveal distinct
consequences of changes in telomerase repeat addition processivity and expression
level on telomere elongation and length maintenance.
PMID- 28495682
TI - A recurring theme in pulmonary fibrosis genetics.
PMID- 28495681
TI - A comparative analysis of costs of single and dual rapid HIV and syphilis
diagnostics: results from a randomised controlled trial in Colombia.
AB - BACKGROUND: HIV and congenital syphilis are major public health burdens
contributing to substantial perinatal morbidity and mortality globally. Although
studies have reported on the costs and cost-effectiveness of rapid diagnostic
tests (RDTs) for syphilis screening within antenatal care in a number of resource
constrained settings, empirical evidence on country-specific cost and estimates
of single RDTs compared with dual RDTs for HIV and syphilis are limited. METHODS:
A cluster randomised controlled study design was used to compare the incremental
costs of two testing algorithms: (1) single RDTs for HIV and syphilis and (2)
dual RDTs for HIV and syphilis, in 12 health facilities in Bogota and Cali,
Colombia. The costs of single HIV and syphilis RDTs and dual HIV and syphilis
RDTs were collected from each of the health facilities. The economic costs per
woman tested for HIV and syphilis and costs per woman treated for syphilis
defined as the total costs required to test and treat one woman for syphilis were
estimated. RESULTS: A total of 2214 women were tested in the study facilities.
Cost per pregnant woman tested and cost per woman treated for syphilis were
US$10.26 and US$607.99, respectively in the single RDT arm. For the dual RDTs,
the cost per pregnant woman tested for HIV and syphilis and cost per woman
treated for syphilis were US$15.89 and US$1859.26, respectively. Overall costs
per woman tested for HIV and syphilis and cost per woman treated for syphilis
were lower in Cali compared with Bogota across both intervention arms. Staff
costs accounted for the largest proportion of costs while treatment costs
comprised <1% of the preventive programme. CONCLUSIONS: Findings show lower
average costs for single RDTs compared with dual RDTs with costs sensitive to
personnel costs and the scale of output at the health facilities. TRIAL
REGISTRATION NUMBER: NCT02454816; results.
PMID- 28495683
TI - Pleuroparenchymal fibroelastosis associated with telomerase reverse transcriptase
mutations.
PMID- 28495684
TI - The Art of Breathing: Pranayama.
PMID- 28495685
TI - "Characterisation of patients with interstitial pneumonia with autoimmune
features." Justin M. Oldham, Ayodeji Adegunsoye, Eleanor Valenzi, Cathryn Lee,
Leah Witt, Lena Chen, Aliya N. Husain, Steven Montner, Jonathan H. Chung, Vincent
Cottin, Aryeh Fischer, Imre Noth, Rekha Vij and Mary E. Strek. Eur Respir J 2016;
47: 1767-1775.
PMID- 28495686
TI - Incidence of non-pulmonary cancer and lung cancer by amount of emphysema and
airway wall thickness: a community-based cohort.
AB - There is limited knowledge about the prognostic value of quantitative computed
tomography (CT) measures of emphysema and airway wall thickness in cancer.The aim
of this study was to investigate if using CT to quantitatively assess the amount
of emphysema and airway wall thickness independently predicts the subsequent
incidence of non-pulmonary cancer and lung cancer.In the GenKOLS study of 2003
2005, 947 ever-smokers performed spirometry and underwent CT examination. The
main predictors were the amount of emphysema measured by the percentage of low
attenuation areas (%LAA) on CT and standardised measures of airway wall thickness
(AWT-PI10). Cancer data from 2003-2013 were obtained from the Norwegian Cancer
Register. The hazard ratio associated with emphysema and airway wall thickness
was assessed using Cox proportional hazards regression for cancer
diagnoses.During 10 years of follow-up, non-pulmonary cancer was diagnosed in 11%
of the subjects with LAA <3%, in 19% of subjects with LAA 3-10%, and in 17% of
subjects with LAA >=10%. Corresponding numbers for lung cancer were 2%, 3% and
11%, respectively. After adjustment, the baseline amount of emphysema remained a
significant predictor of the incidence of non-pulmonary cancer and lung cancer.
Airway wall thickness did not predict cancer independently.This study offers a
strong argument that emphysema is an independent risk factor for both non
pulmonary cancer and lung cancer.
PMID- 28495687
TI - Phenotypes of COPD patients with a smoking history in Central and Eastern Europe:
the POPE Study.
AB - Chronic obstructive pulmonary disease (COPD) represents a major health problem in
Central and Eastern European (CEE) countries; however, there are no data
regarding clinical phenotypes of these patients in this region.Participation in
the Phenotypes of COPD in Central and Eastern Europe (POPE) study was offered to
stable patients with COPD in a real-life setting. The primary aim of this study
was to assess the prevalence of phenotypes according to predefined criteria.
Secondary aims included analysis of differences in symptom load, comorbidities
and pharmacological treatment.3362 patients with COPD were recruited in 10 CEE
countries. 63% of the population were nonexacerbators, 20.4% frequent
exacerbators with chronic bronchitis, 9.5% frequent exacerbators without chronic
bronchitis and 6.9% were classified as asthma-COPD overlap. Differences in the
distribution of phenotypes between countries were observed, with the highest
heterogeneity observed in the nonexacerbator cohort and the lowest heterogeneity
observed in the asthma-COPD cohort. There were statistically significant
differences in symptom load, lung function, comorbidities and treatment between
these phenotypes.The majority of patients with stable COPD in CEE are
nonexacerbators; however, there are distinct differences in surrogates of disease
severity and therapy between predefined COPD phenotypes.
PMID- 28495689
TI - Pleuroparenchymal fibroelastosis associated with telomerase reverse transcriptase
mutations.
PMID- 28495688
TI - The development and validation of the Bronchiectasis Health Questionnaire.
AB - Health-related quality of life or health status is significantly impaired in
bronchiectasis. There is a paucity of brief, simple-to-use, disease-specific
health status measures. The aim of this study was to develop and validate the
Bronchiectasis Health Questionnaire (BHQ), a new health status measure that is
brief and generates a single overall score.Patients with bronchiectasis were
recruited from two outpatient clinics, during a clinically stable stage. The
development of the questionnaire followed three phases: item generation and item
reduction using Rasch analysis, validation, and repeatability testing. The BHQ
was translated into 11 languages using standardised methodology.206 patients with
bronchiectasis completed a preliminary 65-item questionnaire. 55 items were
removed due to redundancy or poor fit to the Rasch model. The final version of
the BHQ consisted of 10 items. Internal consistency was good (Cronbach's
alpha=0.85). Convergent validity of the BHQ with the St George's Respiratory
Questionnaire was high (r= -0.82; p<0.001) and moderate with lung function
(forced expiratory volume in 1 s % predicted r= -0.27; p=0.001). There was a
significant association between BHQ scores and number of exacerbations of
bronchiectasis in the last 12 months (p<0.001), hospital admissions (p=0.001) and
computed tomography scan bronchiectasis pulmonary lobe counts (p<0.001). BHQ
scores were significantly worse in patients with sputum bacterial colonisation
versus no colonisation (p=0.048). The BHQ was highly repeatable after 2 weeks
(intraclass correlation coefficient 0.89).The BHQ is a brief, valid and
repeatable, self-completed health status questionnaire for bronchiectasis that
generates a single total score. It can be used in the clinic to assess
bronchiectasis from the patient's perspective.
PMID- 28495690
TI - Intensive care in thoracic oncology.
AB - The admission of lung cancer patients to intensive care is related to
postprocedural/postoperative care and medical complications due to cancer or its
treatment, but is also related to acute organ failure not directly related to
cancer.Despite careful preoperative risk management and the use of modern
surgical and anaesthetic techniques, thoracic surgery remains associated with
high morbidity, related to the extent of resection and specific comorbidities.
Fast-tracking processes with timely recognition and treatment of complications
favourably influence patient outcome. Postoperative preventive and therapeutic
management has to be carefully planned in order to reduce postoperative morbidity
and mortality.For patients with severe complications, intensive care unit (ICU)
mortality rate ranges from 13% to 47%, and hospital mortality ranges from 24% to
65%. Common predictors of in-hospital mortality are severity scores, number of
failing organs, general condition, respiratory distress and the need for
mechanical ventilation or vasopressors. When considering long-term survival after
discharge, cancer-related parameters retain their prognostic value.Thoracic
surgeons, anesthesiologists, pneumologists, intensivists and oncologists need to
develop close and confident partnerships aimed at implementing evidence-based
patient care, securing clinical pathways for patient management while promoting
education, research and innovation. The final decision on admitting a patient
with lung to the ICU should be taken in close partnership between this medical
team and the patient and his or her relatives.
PMID- 28495691
TI - Screening for pulmonary arterial hypertension in an unselected prospective
systemic sclerosis cohort.
AB - Screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc)
improves outcomes. The DETECT screening algorithm is recommended in a high-risk
SSc subgroup. This study aims to compare prospectively the positive predictive
value of screening using the DETECT algorithm and the 2009 European Society of
Cardiology/European Respiratory Society (ESC/ERS) guidelines, and to compare
their cost-effectiveness in an unselected, day-to-day SSc population. Post hoc,
screening according to the 2015 ESC/ERS guidelines using echocardiographic
parameters alone ("2015 echo screening") or combined with the DETECT algorithm
("2015 combined screening") in high-risk subjects was analysed.195 consecutive
SSc patients included in the Ghent University Hospital SSc cohort were screened
using different algorithms.The referral rate for right heart catheterisation was
32% (63 out of 195 patients) (46/4/13/34/40 patients using the DETECT
algorithm/2009 guidelines/both/2015 echo screening/2015 combined screening).
Right heart catheterisation was performed in 53 patients (84%) (36 (78%)/four
(100%)/13 (100%)/28 (82%)/32 (80%) patients recommended by the DETECT
algorithm/2009 guidelines/both/2015 echo screening/2015 combined screening). PAH
was diagnosed in three patients (incidence 1.5%.year-1, 95% CI 0.5-4.4), in whom
all algorithms recommended a right heart catheterisation. The positive predictive
value was 6% (95% CI 2-17%; three out of 49 patients) for the DETECT algorithm,
18% (95% CI 6-41%; three out of 17 patients) for the 2009 guidelines, 23% (95% CI
8-50%; three out of 13 patients) for both, 11% (95% CI 4-27%; three out of 28
patients) for the 2015 echo screening and 9% (95% CI 3-24%; three out of 32
patients) for the 2015 combined screening. The cost was EUR224/80/90/112 per
patient using the DETECT algorithm/2009 guidelines/2015 echo screening/2015
combined screening.Echocardiography may remain a candidate first step for PAH
screening in SSc.
PMID- 28495693
TI - Tropical Australia is a potential reservoir of non-tuberculous mycobacteria in
cystic fibrosis.
PMID- 28495694
TI - Phenotypes contribute to treatments.
PMID- 28495692
TI - Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease
and familial pulmonary fibrosis.
AB - Despite its high prevalence and mortality, little is known about the pathogenesis
of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Given that
familial pulmonary fibrosis (FPF) and RA-ILD frequently share the usual pattern
of interstitial pneumonia and common environmental risk factors, we hypothesised
that the two diseases might share additional risk factors, including FPF-linked
genes. Our aim was to identify coding mutations of FPF-risk genes associated with
RA-ILD.We used whole exome sequencing (WES), followed by restricted analysis of a
discrete number of FPF-linked genes and performed a burden test to assess the
excess number of mutations in RA-ILD patients compared to controls.Among the 101
RA-ILD patients included, 12 (11.9%) had 13 WES-identified heterozygous mutations
in the TERT, RTEL1, PARN or SFTPC coding regions. The burden test, based on 81 RA
ILD patients and 1010 controls of European ancestry, revealed an excess of TERT,
RTEL1, PARN or SFTPC mutations in RA-ILD patients (OR 3.17, 95% CI 1.53-6.12;
p=9.45*10-4). Telomeres were shorter in RA-ILD patients with a TERT, RTEL1 or
PARN mutation than in controls (p=2.87*10-2).Our results support the contribution
of FPF-linked genes to RA-ILD susceptibility.
PMID- 28495695
TI - Haemodynamically proven pulmonary hypertension in a patient with GATA2 deficiency
associated pulmonary alveolar proteinosis and fibrosis.
PMID- 28495696
TI - Health-related quality of life questionnaires in bronchiectasis: the simplest way
to quantify complexity.
PMID- 28495697
TI - Haemodynamically proven pulmonary hypertension in a patient with GATA2 deficiency
associated pulmonary alveolar proteinosis and fibrosis.
PMID- 28495698
TI - Pulmonary arterial hypertension: screening challenges in systemic sclerosis and
future directions.
PMID- 28495699
TI - American College of Cardiology/American Heart Association (ACC/AHA) Class I
Guidelines for the Treatment of Cholesterol to Reduce Atherosclerotic
Cardiovascular Risk: Implications for US Hispanics/Latinos Based on Findings From
the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).
AB - BACKGROUND: The prevalence estimates of statin eligibility among Hispanic/Latinos
living in the United States under the new 2013 American College of
Cardiology/American Heart Association (ACC/AHA) cholesterol treatment guidelines
are not known. METHODS AND RESULTS: We estimated prevalence of statin eligibility
under 2013 ACC/AHA and 3rd National Cholesterol Education Program Adult Treatment
Panel (NCEP/ATP III) guidelines among Hispanic Community Health Study/Study of
Latinos (n=16 415; mean age 41 years, 40% males) by using sampling weights
calibrated to the 2010 US census. We examined the characteristics of
Hispanic/Latinos treated and not treated with statins under both guidelines. We
also redetermined the statin-therapy eligibility by using black risk estimates
for Dominicans, Cubans, Puerto Ricans, and Central Americans. Compared with
NCEP/ATP III guidelines, statin eligibility increased from 15.9% (95% CI 15.0
16.7%) to 26.9% (95% CI 25.7-28.0%) under the 2013 ACC/AHA guidelines. This was
mainly driven by the >=7.5% atherosclerotic cardiovascular disease risk criteria
(prevalence 13.9% [95% CI 13.0-14.7%]). Of the participants eligible for statin
eligibility under NCEP/ATP III and ACC/AHA guidelines, only 28.2% (95% CI 26.3
30.0%) and 20.6% (95% CI 19.4-21.9%) were taking statins, respectively. Statin
eligible participants who were not taking statins had a higher prevalence of
cardiovascular risk factors compared with statin-eligible participants who were
taking statins. There was no significant increase in statin eligibility when
atherosclerotic cardiovascular disease risk was calculated by using black
estimates instead of recommended white estimates (increase by 1.4%, P=0.12) for
Hispanic/Latinos. CONCLUSIONS: The eligibility of statin therapy increased
consistently across all Hispanic/Latinos subgroups under the 2013 ACC/AHA
guidelines and therefore will potentially increase the number of undertreated
Hispanic/Latinos in the United States.
PMID- 28495700
TI - Visualizing dynamic microvillar search and stabilization during ligand detection
by T cells.
AB - During immune surveillance, T cells survey the surface of antigen-presenting
cells. In searching for peptide-loaded major histocompatibility complexes
(pMHCs), they must solve a classic trade-off between speed and sensitivity. It
has long been supposed that microvilli on T cells act as sensory organs to enable
search, but their strategy has been unknown. We used lattice light-sheet and
quantum dot-enabled synaptic contact mapping microscopy to show that anomalous
diffusion and fractal organization of microvilli survey the majority of opposing
surfaces within 1 minute. Individual dwell times were long enough to discriminate
pMHC half-lives and T cell receptor (TCR) accumulation selectively stabilized
microvilli. Stabilization was independent of tyrosine kinase signaling and the
actin cytoskeleton, suggesting selection for avid TCR microclusters. This work
defines the efficient cellular search process against which ligand detection
takes place.
PMID- 28495703
TI - News at a glance.
PMID- 28495702
TI - Academia under fire in Hungary.
PMID- 28495701
TI - Poor human olfaction is a 19th-century myth.
AB - It is commonly believed that humans have a poor sense of smell compared to other
mammalian species. However, this idea derives not from empirical studies of human
olfaction but from a famous 19th-century anatomist's hypothesis that the
evolution of human free will required a reduction in the proportional size of the
brain's olfactory bulb. The human olfactory bulb is actually quite large in
absolute terms and contains a similar number of neurons to that of other mammals.
Moreover, humans have excellent olfactory abilities. We can detect and
discriminate an extraordinary range of odors, we are more sensitive than rodents
and dogs for some odors, we are capable of tracking odor trails, and our
behavioral and affective states are influenced by our sense of smell.
PMID- 28495704
TI - Pinpointing HIV spread in Africa poses risks.
PMID- 28495705
TI - Who will watch the Amazon?
PMID- 28495706
TI - In a first, natural selection defeats a biocontrol insect.
PMID- 28495707
TI - Newest member of human family is surprisingly young.
PMID- 28495708
TI - Pocket-sized sequencers start to pay off big.
PMID- 28495709
TI - China cracks down on coastal fisheries.
PMID- 28495710
TI - NIH to cap grants for well-funded investigators.
PMID- 28495711
TI - Fears of Ebola resurgence quickly dispelled in Liberia.
PMID- 28495712
TI - Where have all the insects gone?
PMID- 28495713
TI - Saying goodbye to glaciers.
PMID- 28495714
TI - Charge delivery goes the distance.
PMID- 28495715
TI - Coupling and sharing when life is hard.
PMID- 28495716
TI - Keeping in touch with the ER network.
PMID- 28495718
TI - Biodefense in the 21st century.
PMID- 28495717
TI - Myriad take two: Can genomic databases remain secret?
PMID- 28495719
TI - Faulty logic.
PMID- 28495721
TI - Tracing our ancestors in cave sediments.
PMID- 28495720
TI - Why science? Scientists share their stories.
PMID- 28495722
TI - Personalized printing for human health.
PMID- 28495723
TI - Shipping iron around in small packages.
PMID- 28495724
TI - Intricacy anchored by uranium.
PMID- 28495725
TI - How much water is in that exoplanet?
PMID- 28495726
TI - Resolution achieved.
PMID- 28495727
TI - ER-PM contacts in nonclathrin endocytosis.
PMID- 28495729
TI - Cancer immunotherapy according to GARP.
PMID- 28495728
TI - Mapping the world's dry forests.
PMID- 28495731
TI - Search and capture in space and time.
PMID- 28495730
TI - Humans have a good sense of smell.
PMID- 28495732
TI - As with donuts, the holes matter.
PMID- 28495733
TI - Maximizing growth by sharing.
PMID- 28495734
TI - Toward a world without glaciers.
PMID- 28495735
TI - A more pathological amyloid-beta oligomer.
PMID- 28495737
TI - Disrupting housefly gene reverses sex.
PMID- 28495736
TI - Tug of war with anti-PD-1.
PMID- 28495739
TI - Targeting senescence to combat osteoarthritis.
PMID- 28495738
TI - Macrophages feel the heart beat.
PMID- 28495740
TI - Crop resistance to parasites.
PMID- 28495742
TI - Quantum dots visibly forge carbon bonds.
PMID- 28495741
TI - An elusive magnet in an atomic cloud.
PMID- 28495743
TI - A probable dwarf planet beyond Neptune.
PMID- 28495744
TI - Selection acts on the neighbors.
PMID- 28495745
TI - Three-dimensional holey-graphene/niobia composite architectures for ultrahigh
rate energy storage.
AB - Nanostructured materials have shown extraordinary promise for electrochemical
energy storage but are usually limited to electrodes with rather low mass loading
(~1 milligram per square centimeter) because of the increasing ion diffusion
limitations in thicker electrodes. We report the design of a three-dimensional
(3D) holey-graphene/niobia (Nb2O5) composite for ultrahigh-rate energy storage at
practical levels of mass loading (>10 milligrams per square centimeter). The
highly interconnected graphene network in the 3D architecture provides excellent
electron transport properties, and its hierarchical porous structure facilitates
rapid ion transport. By systematically tailoring the porosity in the holey
graphene backbone, charge transport in the composite architecture is optimized to
deliver high areal capacity and high-rate capability at high mass loading, which
represents a critical step forward toward practical applications.
PMID- 28495748
TI - HAT-P-26b: A Neptune-mass exoplanet with a well-constrained heavy element
abundance.
AB - A correlation between giant-planet mass and atmospheric heavy elemental abundance
was first noted in the past century from observations of planets in our own Solar
System and has served as a cornerstone of planet-formation theory. Using data
from the Hubble and Spitzer Space Telescopes from 0.5 to 5 micrometers, we
conducted a detailed atmospheric study of the transiting Neptune-mass exoplanet
HAT-P-26b. We detected prominent H2O absorption bands with a maximum base-to-peak
amplitude of 525 parts per million in the transmission spectrum. Using the water
abundance as a proxy for metallicity, we measured HAT-P-26b's atmospheric heavy
element content ([Formula: see text] times solar). This likely indicates that HAT
P-26b's atmosphere is primordial and obtained its gaseous envelope late in its
disk lifetime, with little contamination from metal-rich planetesimals.
PMID- 28495747
TI - Reticulon 3-dependent ER-PM contact sites control EGFR nonclathrin endocytosis.
AB - The integration of endocytic routes is critical to regulate receptor signaling. A
nonclathrin endocytic (NCE) pathway of the epidermal growth factor receptor
(EGFR) is activated at high ligand concentrations and targets receptors to
degradation, attenuating signaling. Here we performed an unbiased molecular
characterization of EGFR-NCE. We identified NCE-specific regulators, including
the endoplasmic reticulum (ER)-resident protein reticulon 3 (RTN3) and a specific
cargo, CD147. RTN3 was critical for EGFR/CD147-NCE, promoting the creation of
plasma membrane (PM)-ER contact sites that were required for the formation and/or
maturation of NCE invaginations. Ca2+ release at these sites, triggered by
inositol 1,4,5-trisphosphate (IP3)-dependent activation of ER Ca2+ channels, was
needed for the completion of EGFR internalization. Thus, we identified a
mechanism of EGFR endocytosis that relies on ER-PM contact sites and local Ca2+
signaling.
PMID- 28495749
TI - Holliday junction resolvases mediate chloroplast nucleoid segregation.
AB - Holliday junctions, four-stranded DNA structures formed during homologous
recombination, are disentangled by resolvases that have been found in prokaryotes
and eukaryotes but not in plant organelles. Here, we identify monokaryotic
chloroplast 1 (MOC1) as a Holliday junction resolvase in chloroplasts by
analyzing a green alga Chlamydomonas reinhardtii mutant defective in chloroplast
nucleoid (DNA-protein complex) segregation. MOC1 is structurally similar to a
bacterial Holliday junction resolvase, resistance to ultraviolet (Ruv) C, and
genetically conserved among green plants. Reduced or no expression of MOC1 in
Arabidopsis thaliana leads to growth defects and aberrant chloroplast nucleoid
segregation. In vitro biochemical analysis and high-speed atomic force
microscopic analysis revealed that A. thaliana MOC 1 (AtMOC1) binds and cleaves
the core of Holliday junctions symmetrically. MOC1 may mediate chloroplast
nucleoid segregation in green plants by resolving Holliday junctions.
PMID- 28495746
TI - Restored iron transport by a small molecule promotes absorption and
hemoglobinization in animals.
AB - Multiple human diseases ensue from a hereditary or acquired deficiency of iron
transporting protein function that diminishes transmembrane iron flux in distinct
sites and directions. Because other iron-transport proteins remain active, labile
iron gradients build up across the corresponding protein-deficient membranes.
Here we report that a small-molecule natural product, hinokitiol, can harness
such gradients to restore iron transport into, within, and/or out of cells. The
same compound promotes gut iron absorption in DMT1-deficient rats and ferroportin
deficient mice, as well as hemoglobinization in DMT1- and mitoferrin-deficient
zebrafish. These findings illuminate a general mechanistic framework for small
molecule-mediated site- and direction-selective restoration of iron transport.
They also suggest that small molecules that partially mimic the function of
missing protein transporters of iron, and possibly other ions, may have potential
in treating human diseases.
PMID- 28495753
TI - Lucking into science.
PMID- 28495750
TI - The extent of forest in dryland biomes.
AB - Dryland biomes cover two-fifths of Earth's land surface, but their forest area is
poorly known. Here, we report an estimate of global forest extent in dryland
biomes, based on analyzing more than 210,000 0.5-hectare sample plots through a
photo-interpretation approach using large databases of satellite imagery at (i)
very high spatial resolution and (ii) very high temporal resolution, which are
available through the Google Earth platform. We show that in 2015, 1327 million
hectares of drylands had more than 10% tree-cover, and 1079 million hectares
comprised forest. Our estimate is 40 to 47% higher than previous estimates,
corresponding to 467 million hectares of forest that have never been reported
before. This increases current estimates of global forest cover by at least 9%.
PMID- 28495751
TI - Male sex in houseflies is determined by Mdmd, a paralog of the generic splice
factor gene CWC22.
AB - Across species, animals have diverse sex determination pathways, each consisting
of a hierarchical cascade of genes and its associated regulatory mechanism.
Houseflies have a distinctive polymorphic sex determination system in which a
dominant male determiner, the M-factor, can reside on any of the chromosomes. We
identified a gene, Musca domesticamale determiner (Mdmd), as the M-factor. Mdmd
originated from a duplication of the spliceosomal factor gene CWC22
(nucampholin). Targeted Mdmd disruption results in complete sex reversal to
fertile females because of a shift from male to female expression of the
downstream genes transformer and doublesex The presence of Mdmd on different
chromosomes indicates that Mdmd translocated to different genomic sites. Thus, an
instructive signal in sex determination can arise by duplication and
neofunctionalization of an essential splicing regulator.
PMID- 28495754
TI - PHD3 is a transcriptional coactivator of HIF-1alpha in nucleus pulposus cells
independent of the PKM2-JMJD5 axis.
AB - The role of prolyl hydroxylase (PHD)-3 as a hypoxia inducible factor (HIF)-1alpha
cofactor is controversial and remains unknown in skeletal tissues. We
investigated whether PHD3 controls HIF-1 transcriptional activity in nucleus
pulposus (NP) cells through the pyruvate kinase muscle (PKM)-2-Jumonji domain-
containing protein (JMJD5) axis. PHD3-/- mice (12.5 mo old) showed increased
incidence of intervertebral disc degeneration with a concomitant decrease in
expression of the HIF-1alpha targets VEGF-A, glucose transporter-1, and lactate
dehydrogenase A. PHD3 silencing decreased hypoxic activation of HIF-1alpha C
terminal transactivation domain (C-TAD), but not HIF-1alpha-N-terminal-(N)-TAD or
HIF-2alpha-TAD. Moreover, PHD3 suppression in NP cells resulted in decreased HIF
1alpha enrichment on target promoters and lower expression of select HIF-1
targets. Contrary to other cell types, manipulation of PKM2 and JMJD5 levels had
no effect on HIF-1 activity in NP cells. Likewise, stabilization of tetrameric
PKM2 by a chemical approach had no effect on PHD3-dependent HIF-1 activity.
Coimmunoprecipitation assays showed lack of association between HIF-1alpha and
PKM2 in NP cells. Results support the role of the PHD3 as a cofactor for HIF-1,
independent of PKM2-JMJD5.-Schoepflin, Z. R., Silagi, E. S., Shapiro, I. M.,
Risbud, M. V. PHD3 is a transcriptional coactivator of HIF-1alpha in nucleus
pulposus cells independent of the PKM2-JMJD5 axis.
PMID- 28495755
TI - Intestinal microbiota contributes to colonic epithelial changes in simulated
microgravity mouse model.
AB - Exposure to microgravity leads to alterations in multiple systems, but
microgravity-related changes in the gastrointestinal tract and its clinical
significance have not been well studied. We used the hindlimb unloading (HU)
mouse model to simulate a microgravity condition and investigated the changes in
intestinal microbiota and colonic epithelial cells. Compared with ground-based
controls (Ctrls), HU affected fecal microbiota composition with a profile that
was characterized by the expansion of Firmicutes and decrease of Bacteroidetes.
The colon epithelium of HU mice showed decreased goblet cell numbers, reduced
epithelial cell turnover, and decreased expression of genes that are involved in
defense and inflammatory responses. As a result, increased susceptibility to
dextran sulfate sodium-induced epithelial injury was observed in HU mice.
Cohousing of Ctrl mice with HU mice resulted in HU-like epithelial changes in
Ctrl mice. Transplantation of feces from Ctrl to HU mice alleviated these
epithelial changes in HU mice. Results indicate that HU changes intestinal
microbiota, which leads to altered colonic epithelial cell homeostasis, impaired
barrier function, and increased susceptibility to colitis. We further demonstrate
that alteration in gastrointestinal motility may contribute to HU-associated
dysbiosis. These animal results emphasize the necessity of evaluating astronauts'
intestinal homeostasis during distant space travel.-Shi, J., Wang, Y., He, J.,
Li, P., Jin, R., Wang, K., Xu, X., Hao, J., Zhang, Y., Liu, H., Chen, X., Wu, H.,
Ge, Q. Intestinal microbiota contributes to colonic epithelial changes in
simulated microgravity mouse model.
PMID- 28495756
TI - Cystic fibrosis transmembrane conductance regulator mediates tenogenic
differentiation of tendon-derived stem cells and tendon repair: accelerating
tendon injury healing by intervening in its downstream signaling.
AB - Tendons are a mechanosensitive tissue, which enables them to transmit to bone
forces that are derived from muscle. Patients with tendon injuries, such as
tendinopathy or tendon rupture, were often observed with matrix degeneration, and
the healing of tendon injuries remains a challenge as a result of the limited
understanding of tendon biology. Our study demonstrates that the stretch-mediated
activation channel, cystic fibrosis transmembrane conductance regulator (CFTR),
was up-regulated in tendon-derived stem cells (TDSCs) during tenogenic
differentiation under mechanical stretching. Tendon tissues in CFTR-dysfunctional
DF508 mice exhibited irregular cell arrangement, uneven fibril diameter
distribution, weak mechanical properties, and less matrix formation in a tendon
defect model. Moreover, both tendon tissues and TDSCs isolated from DF508 mice
showed significantly decreased levels of tendon markers, such as scleraxis,
tenomodulin, Col1A1 (collagen type I alpha 1 chain), and decorin Furthermore, by
RNA sequencing analysis, we demonstrated that Wnt/beta-catenin signaling was
abnormally activated in TDSCs from DF508 mice, thereby further activating the
pERK1/2 signaling pathway. Of most importance, we found that intervention in
pERK1/2 signaling could promote tenogenic differentiation and tendon regeneration
both in vitro and in vivo Taken together, our study demonstrates that CFTR plays
an important role in tenogenic differentiation and tendon regeneration by
inhibiting the beta-catinin/pERK1/2 signaling pathway. The therapeutic strategy
of intervening in the CFTR/beta-catenin/pERK1/2 regulatory axis may be helpful
for accelerating tendon injury healing, which has implications for tendon injury
management.-Liu, Y., Xu, J., Xu, L., Wu, T., Sun, Y., Lee, Y.-W., Wang, B., Chan,
H.-C., Jiang, X., Zhang, J., Li, G. Cystic fibrosis transmembrane conductance
regulator mediates tenogenic differentiation of tendon-derived stem cells and
tendon repair: accelerating tendon injury healing by intervening in its
downstream signaling.
PMID- 28495757
TI - Complete Genome Sequence of a Novel Multidrug-Resistant Klebsiella pneumoniae
Phage, vB_Kpn_IME260.
AB - Klebsiella pneumoniae is the most common clinically important opportunistic
bacterial pathogen and its infection is often iatrogenic. Its drug resistance
poses a grave threat to public health. The genomic data reported here comprise an
important resource for research on phage therapy in the control of drug-resistant
bacteria.
PMID- 28495758
TI - Draft Genome Sequences of Enterohemorrhagic Escherichia coli O103:H2 Strains
Isolated from Feces of Feedlot Cattle.
AB - The enterohemorrhagic pathotype represents a minor proportion of the Escherichia
coli O103 strains shed in the feces of cattle. We report here the genome
sequences of 43 strains of enterohemorrhagic E. coli (EHEC) O103:H2 isolated from
feedlot cattle feces. The genomic analysis will provide information on the
genetic diversity and virulence potential of bovine EHEC O103.
PMID- 28495759
TI - Complete Genome Sequences of Two Phage-Like Plasmids Carrying the CTX-M-15
Extended-Spectrum beta-Lactamase Gene.
AB - Two similar phage-like plasmids carrying CTX-M-15 resistance cassettes were
identified from two environmental Escherichia coli isolates. They demonstrate
strong nucleotide sequence identity to the phage-like plasmid pECOH89 and
Salmonella bacteriophage SSU5.
PMID- 28495760
TI - AnCo3, a New Member of the Emerging Family of Phage-Like Plasmids.
AB - A phage-like plasmid isolated from a clinical isolate of Salmonella enterica
serovar Derby has strong nucleotide sequence identity to the phage-like plasmids
pSTM_phi isolated from Salmonella enterica serovar Typhimurium L495, AnCo1 and
AnCo2 from Escherichia coli 243 and Escherichia coli 244, and the virulent
Salmonella-specific SSU5 bacteriophage.
PMID- 28495761
TI - Genome Sequence of a Bovine Rhinitis B Virus Identified in Cattle in Sweden.
AB - A bovine rhinitis B virus, identified in a calf from Sweden, was genetically
characterized. The complete polyprotein was recovered, and phylogenetic analysis
showed that this virus has the highest similarity to a bovine rhinitis B virus
previously identified in Mexico.
PMID- 28495763
TI - Draft Genome Sequences of Serratia marcescens Strains CAPREx SY13 and CAPREx SY21
Isolated from Yams.
AB - Serratia marcescens strains CAPREx SY13 and CAPREx SY21 were isolated from
Ghanaian yams from a London market. The draft genomes suggest that the strains
are similar, with genomes of 5,308,004 and 5,157,134 bp and 59.35 and 59.62 G+C%,
respectively. The genes necessary for prodigiosin biosynthesis were present in
both strains.
PMID- 28495762
TI - Draft Genome Sequences of 25 Listeria monocytogenes Isolates Associated with
Human Clinical Listeriosis in Ireland.
AB - Listeria monocytogenes is a Gram-positive opportunistic pathogen that is the
causative agent of listeriosis. Here, we report the draft genome sequences of 25
L. monocytogenes strains isolated from patients with clinical listeriosis in the
Republic of Ireland between 2013 and 2015.
PMID- 28495764
TI - Draft Genome Sequence of Geobacillus sp. LEMMY01, a Thermophilic Bacterium
Isolated from the Site of a Burning Grass Pile.
AB - We report here the 3,586,065-bp draft genome of Geobacillus sp. LEMMY01, which
was isolated (axenic culture) from a thermophilic chemolitoautotrophic consortium
obtained from the site of a burning grass pile. The genome contains biosynthetic
gene clusters coding for secondary metabolites, such as terpene and lantipeptide,
confirming the biotechnological potential of this strain.
PMID- 28495765
TI - Complete Genome Sequence of Bacteriophage SEN8, a Temperate Phage Isolated from
Salmonella enterica subsp. salamae.
AB - A temperate phage, SEN8, having a broad activity against pathogenic Salmonella
serovars, was isolated from Salmonella enterica subsp. salamae strain Sen8. The
complete genome sequence of phage SEN8 was determined (35,203 bp) and showed
relatedness to P2-like phages (Salmonella phages Fels-2 and RE-2010).
PMID- 28495766
TI - Ten Genome Sequences of Human and Livestock Isolates of Bacillus anthracis from
the Country of Georgia.
AB - Bacillus anthracis causes the acute fatal disease anthrax, is a proven biological
weapon, and is endemic in Georgia, where human and animal cases are reported
annually. Here, we present whole-genome sequences of 10 historical B. anthracis
strains from Georgia.
PMID- 28495767
TI - Complete Genome Sequences of 12 Isolates of Listeria monocytogenes Belonging to
Serotypes 1/2a, 1/2b, and 4b Obtained from Food Products and Food-Processing
Environments in Canada.
AB - Listeria monocytogenes is the etiological agent for an often fatal foodborne
illness known as listeriosis. Here, we present the complete genome sequences of
12 L. monocytogenes isolates representing the three most common serotypes of this
pathogen (1/2a, 1/2b, and 4b), collected in Canada from different food products
and environmental sources.
PMID- 28495768
TI - Complete Genome Sequence of an Enterovirus 71 Strain Isolated from the
Cerebrospinal Fluid of a Child with Severe Hand-Foot-and-Mouth Disease in Yunnan,
China, 2013.
AB - The complete genome sequence of the enterovirus 71 strain CSF15/YN/CHN/2013,
first isolated from cerebrospinal fluid of a child in Yunnan, China, in 2013, was
determined. According to the phylogenetic and homogeneity analyses, the isolate
was assigned to subgenotype C4a.
PMID- 28495769
TI - Draft Genome Sequence of Bacillus toyonensis VU-DES13, Isolated from Folsomia
candida (Collembola: Entomobryidae).
AB - We present here the draft genome of Bacillus toyonensis VU-DES13, which was
isolated from the midgut of the soil-living springtail Folsomia candida Previous
research revealed the presence of gene clusters for the biosynthesis of various
secondary metabolites, including beta-lactam antibiotics, in the host's genome.
The genome data are discussed in the light of the antimicrobial properties
against fungi and oomycetes and a high level of beta-lactam resistance of the
isolate.
PMID- 28495770
TI - Complete Genome Sequence of the Bacterium Bacillus circulans Jordan Strain 32352.
AB - Here, we report the complete genome sequence for the Bacillus circulans Jordan
strain 32352. This species is a soil dwelling bacterium that expresses glycosyl
hydrolase enzymes degrading pneumococcal capsular polysaccharides.
PMID- 28495771
TI - Complete Genome Sequence of the Disinfectant Susceptibility Testing Reference
Strain Staphylococcus aureus subsp. aureus ATCC 6538.
AB - We report here the complete genome sequence of the methicillin-sensitive
Staphylococcus aureus subsp. aureus strain ATCC 6538 (FDA 209, DSM 799, WDCM
00032, and NCTC 10788).
PMID- 28495772
TI - Complete Genome Sequence of the Livestock-Associated Methicillin-Resistant Strain
Staphylococcus aureus subsp. aureus 08S00974 (Sequence Type 398).
AB - We report here the complete genome sequence of the livestock-associated
methicillin-resistant Staphylococcus aureus strain 08S00974 from sequence type
398 (ST398 LA-MRSA) isolated from a fatting pig at a farm in Germany.
PMID- 28495773
TI - New Sequence Types of Vibrio parahaemolyticus Isolated from a Malaysian
Aquaculture Pond, as Revealed by Whole-Genome Sequencing.
AB - The acquisition of Photorhabdus insect-related (Pir) toxin-like genes in Vibrio
parahaemolyticus has been linked to hepatopancreatic necrosis disease in shrimp.
We report the whole-genome sequences of genetically virulent and avirulent V.
parahaemolyticus isolated from a Malaysian aquaculture pond and show that they
represent previously unreported sequence types of V. parahaemolyticus.
PMID- 28495774
TI - Whole-Genome Sequence of Endophytic Plant Growth-Promoting Escherichia coli
USML2.
AB - Escherichia coli strain USML2 was originally isolated from the inner leaf tissues
of surface-sterilized phytopathogenic-free oil palm (Elaeis guineensis Jacq.). We
present here the whole-genome sequence of this plant-endophytic strain. The
genome consists of a single circular chromosome of 4,502,758 bp, 4,315 predicted
coding sequences, and a G+C content of 50.8%.
PMID- 28495775
TI - Complete Coding Sequence of a Case of Chikungunya Virus Imported into Australia.
AB - A case of chikungunya virus infection was imported from India into Australia in
late 2016. Infection was diagnosed by real-time reverse transcription-PCR and
confirmed by culture isolation and genome sequencing. Phylogenetic analysis of
the genome sequence indicated that the virus grouped with the east/central/south
African genotype.
PMID- 28495776
TI - Analysis of an RNA-seq Strand-Specific Library from an East Timorese Cucumber
Sample Reveals a Complete Cucurbit aphid-borne yellows virus Genome.
AB - Analysis of an RNA-seq library from cucumber leaf RNA extracted from a fast
technology for analysis of nucleic acids (FTA) card revealed the first complete
genome of Cucurbit aphid-borne yellows virus (CABYV) from East Timor. We compare
it with 35 complete CABYV genomes from other world regions. It most resembled the
genome of the South Korean isolate HD118.
PMID- 28495777
TI - Complete Annotated Genome Sequences of Two Shiga Toxin-Producing Escherichia coli
Strains and One Atypical Enteropathogenic E. coli Strain, Isolated from Naturally
Colonized Cattle of German Origin.
AB - Shiga toxin-producing Escherichia coli (STEC) strains are important zoonotic
enteric pathogens with the main reservoir in cattle. Here, we present the genomes
of two STEC strains and one atypical enteropathogenic E. coli strain from cattle
origin, obtained during a longitudinal study in German cattle herds.
PMID- 28495778
TI - Draft Genome of the Heterotrophic Iron-Oxidizing Bacterium "Acidibacillus
ferroxidans" Huett2, Isolated from a Mine Drainage Ditch in Freiberg, Germany.
AB - Here, we communicate the draft genome of "Acidibacillus ferrooxidans" Huett2, a
novel strain of an acidophilic, heterotrophic, iron-oxidizing bacterium belonging
to the phylum Firmicutes It was isolated from a water drainage system of a former
minefield in Freiberg, Germany.
PMID- 28495779
TI - Complete Genome Sequence of Mycoplasma bovis Strain 08M.
AB - Mycoplasma bovis is a major bacterial pathogen that can cause respiratory
disease, mastitis, and arthritis in cattle. We report here the complete and
annotated genome sequence of M. bovis strain 08M, isolated from a calf lung with
pneumonia in China.
PMID- 28495780
TI - Genome Sequences of Listeria monocytogenes Strains with Resistance to Arsenic.
AB - Listeria monocytogenes frequently exhibits resistance to arsenic. We report here
the draft genome sequences of eight genetically diverse arsenic-resistant L.
monocytogenes strains from human listeriosis and food-associated environments.
The availability of these genomes will help elucidate the role of heavy-metal
resistance in the ecology of L. monocytogenes.
PMID- 28495781
TI - Draft Genome Sequence of Lawsonia intracellularis Strain E40504, Isolated from a
Horse Diagnosed with Equine Proliferative Enteropathy.
AB - Reported herein is the draft genome sequence of equine-origin Lawsonia
intracellularis strain E40504, an obligate intracellular bacterium and the
etiological agent of equine proliferative enteropathy. The 1.69-Mb draft genome
sequence includes 1,380 protein-coding genes and 49 RNA genes, and it lacks a
genomic island reported in swine-origin L. intracellularis strain PHE/MN1-00.
PMID- 28495782
TI - Draft Genome Sequence of Staphylococcus fleurettii Strain MBTS-1 Isolated from
Cucumber.
AB - The draft genome of Staphylococcus fleurettii MBTS-1, isolated from cucumber in
northern Germany, was sequenced. Analysis showed that the assembled genome had a
size of 2,582,128 bp with a predicted total of 2,491 protein-encoding genes, 9
rRNAs, 5 ncRNAs, and 44 tRNAs. This strain did not contain plasmid DNA.
PMID- 28495783
TI - Draft Genome Sequence of Streptococcus dysgalactiae subsp. equisimilis Strain
C161L1 Isolated in Vellore, India.
AB - Streptococcus dysgalactiae subsp. equisimilis belongs to the beta-hemolytic group
C and G pyogenic group of streptococci. Here, we report the draft genome of the
S. dysgalactiae subsp. equisimilis strain C161L1 from Vellore, a region in
southern India with a high incidence rate of S. dysgalactiae subsp. equisimilis
infection. This genome is 2.1 Mb long, with a 39.82% G+C content, and encodes
2,022 genes.
PMID- 28495784
TI - Implication of Sialidases in Salmonella Infection: Genome Release of Sialidase
Knockout Strains from Salmonella enterica Serovar Typhimurium LT2.
AB - Sialidases, which are widely distributed in nature, cleave the alpha-ketosidic
bond of terminal sialic acid residue. These emerging virulence factors degrade
the host glycan. We report here the release of seven sialidase and one sialic
acid transporter deletion in Salmonella enterica serovar Typhimurium strain LT2,
which are important in cellular invasion during infection.
PMID- 28495785
TI - Draft Genome Sequence of Plant Growth-Promoting Endophytic Streptomyces sp. GKU
895 Isolated from the Roots of Sugarcane.
AB - Streptomyces sp. GKU 895 is an endophytic actinomycete isolated from the roots of
sugarcane. GKU 895 has a genome of 8.3 Mbp and the genome exhibits adaptations
related to plant growth-promoting activity. It also has extensive specialized
metabolite biosynthetic gene clusters apparent in its genome.
PMID- 28495786
TI - Speaking fluently with baclofen?
AB - Baclofen is a new and promising pharmacological compound for the treatment of
alcohol dependence (AD). Although several randomised trials found a reduction of
craving and higher abstinence rates with low and high doses of baclofen, others
failed to show positive effects. In this case study, the successful treatment of
a patient with AD with daily 120 mg of baclofen is described. In addition to a
decrease in alcohol use, we observed the cessation of stuttering during treatment
with baclofen, reoccurrence of stuttering following discontinuation, and
cessation of stuttering after reinstatement of the treatment. Based on this
observation, the direct effects of baclofen on muscle relaxation and anxiety
reduction and its indirect effect on dopaminergic inhibition, we believe that
baclofen might be a new treatment for stuttering. Further research into the
effect of baclofen on stuttering is warranted.
PMID- 28495787
TI - Screening contacts of patients with extrapulmonary TB for latent TB infection.
AB - 2016 TB National Institute for Health and Care Excellence (NICE) guidelines imply
that contacts of extrapulmonary TB do not require screening for latent TB
infection. At our high TB prevalence site, we identified 189 active cases of TB
for whom there were 698 close contacts. 29.1% of the contacts of pulmonary TB and
10.7% of the contacts of extrapulmonary TB had active or latent TB infection.
This supports screening contacts of extrapulmonary TB at our site and presents a
way to access high-risk individuals. We propose to continue to screen the
contacts of our patients with extrapulmonary TB and recommend other TB units
audit their local results.
PMID- 28495788
TI - Contraception advice for women with epilepsy.
PMID- 28495789
TI - Dietary, nondigestible oligosaccharides and Bifidobacterium breve M-16V suppress
allergic inflammation in intestine via targeting dendritic cell maturation.
AB - Dietary intervention with short-chain galacto-oligosaccharides (scGOS), long
chain fructo-oligosaccharides (lcFOS) and Bifidobacterium breve M-16V (Bb)
(GF/Bb) suppresses food allergic symptoms in mice, potentially via intestinal
epithelial cell (IEC)-derived galectin-9. Furthermore, in vitro studies showed
galacto- and fructo-oligosaccharides (GF) to enhance the immunomodulatory
capacity of a TLR9 ligand representing bacterial CpG DNA when exposed to IEC. In
this study, we investigated whether GF/Bb modulates dendritic cells (DCs) and
subsequent Th2 and regulatory T cell (Treg) frequency in the small intestinal
lamina propria (SI-LP). BALB/c mice were fed GF/Bb during oral OVA sensitization.
DC and T cell phenotype were determined in SI-LP mononuclear cells using flow
cytometry. Murine bone marrow-derived DCs (BMDCs) were exposed to recombinant
galectin-9 or human monocyte-derived DCs (moDCs) and were cultured in IEC
conditioned medium from GF and TLR9 ligand-exposed HT-29 cells. GF/Bb reduced
allergic symptoms and enhanced serum galectin-9 levels, while suppressing
activation, restoring phagocytic capacity, and normalizing CD103 expression of SI
LP DCs of OVA-allergic mice. In vitro, galectin-9 suppressed LPS-induced
activation markers and cytokine secretion by BMDCs, and IEC-conditioned medium
suppressed moDC activation in a galectin-9-dependent manner. Besides suppression
of SI-LP DC activation, dietary GF/Bb also lowered the frequency of activated Th2
cells, while enhancing Treg in the SI-LP of OVA-allergic mice compared to the
control diet. Dietary intervention with GF/Bb enhances galectin-9 and suppresses
allergic symptoms of OVA-allergic mice in association with reduced intestinal DC
and Th2 activation and increased Treg frequency in these mice.
PMID- 28495790
TI - Systemic inflammatory response syndrome-related lymphopenia is associated with
adenosine A1 receptor dysfunction.
AB - SIRS is associated with lymphopenia, and prolonged lymphopenia of septic patients
has been associated with increased mortality risk. We hypothesize that elevated
adenosine during SIRS down-regulates Gi-coupled A1R, which signals an effect that
sensitizes a cAMP-dependent lymphotoxic response. In this study, we evaluate the
role of adenosine in SIRS-mediated lymphopenia and impaired IL-15 production.
Cecal ligation and puncture was used to induce sepsis-associated SIRS in mice.
BMDCs were cultured and used to measure the effect of adenosine on IL-15. We
found that A1R mRNA levels were significantly down-regulated and A1R-dependent Gi
activity was abolished in T cells of septic mice. In accordance, cAMP was
elevated in isolated T cells from cecal ligation and puncture compared with sham
treated mice. Similar to septic mice, leukopenia was evident in sham A1R-KO mice,
after treatment with the A1R antagonist (8-cyclopentyl-1,3-dipropylxanthine), or
after A1R desensitization. In contrast, A2AR-KO mice were protected from
leukopenia. In addition, we observed that septic A1R-KO mice exhibited low IL-15
levels. Cultured BMDC agonists of A2AR and A2BR inhibited IL-15 production and
adenosine blocked IL-15-dependent proliferation of cytotoxic T cells that were
cocultured with stimulated BMDCs. To conclude, we suggest that SIRS-associated
lymphopenia is initiated by A1R desensitization and adenosine-mediated inhibition
of IL-15 production is part of the mechanism that accounts for the delay in
leukopenia recovery in patients with severe sepsis. Interference with adenosine
signaling may thus be potentially beneficial for septic patients with leukopenia.
PMID- 28495791
TI - Death rate now rising in UK's poorest infants.
PMID- 28495792
TI - CD70 reverse signaling enhances NK cell function and immunosurveillance in CD27
expressing B-cell malignancies.
AB - The interaction of the tumor necrosis factor receptor (TNFR) CD27 with its ligand
CD70 is an emerging target to treat cancer. CD27 signaling provides costimulatory
signals to cytotoxic T cells but also increases the frequency of regulatory T
cells. Similar to other TNFR ligands, CD70 has been shown to initiate
intracellular signaling pathways (CD70 reverse signaling). CD27 is expressed on a
majority of B-cell non-Hodgkin lymphoma, but its role in the immune control of
lymphoma and leukemia is unknown. We therefore generated a cytoplasmic deletion
mutant of CD27 (CD27-trunc) to study the role of CD70 reverse signaling in the
immunosurveillance of B-cell malignancies in vivo. Expression of CD27-trunc on
malignant cells increased the number of tumor-infiltrating interferon gamma
producing natural killer (NK) cells. In contrast, the antitumoral T-cell response
remained largely unchanged. CD70 reverse signaling in NK cells was mediated via
the AKT signaling pathway and increased NK cell survival and effector function.
The improved immune control by activated NK cells prolonged survival of CD27
trunc-expressing lymphoma-bearing mice. Finally, CD70 reverse signaling enhanced
survival and effector function of human NK cells in a B-cell acute lymphoblastic
leukemia xenotransplants model. Therefore, CD70 reverse signaling in NK cells
contributes to the immune control of CD27-expressing B-cell lymphoma and
leukemia.
PMID- 28495793
TI - USP7 inhibition alters homologous recombination repair and targets CLL cells
independently of ATM/p53 functional status.
AB - The role of deubiquitylase ubiquitin-specific protease 7 (USP7) in the regulation
of the p53-dependent DNA damage response (DDR) pathway is well established.
Whereas previous studies have mostly focused on the mechanisms underlying how
USP7 directly controls p53 stability, we recently showed that USP7 modulates the
stability of the DNA damage responsive E3 ubiquitin ligase RAD18. This suggests
that targeting USP7 may have therapeutic potential even in tumors with defective
p53 or ibrutinib resistance. To test this hypothesis, we studied the effect of
USP7 inhibition in chronic lymphocytic leukemia (CLL) where the ataxia
telangiectasia mutated (ATM)-p53 pathway is inactivated with relatively high
frequency, leading to treatment resistance and poor clinical outcome. We
demonstrate that USP7 is upregulated in CLL cells, and its loss or inhibition
disrupts homologous recombination repair (HRR). Consequently, USP7 inhibition
induces significant tumor-cell killing independently of ATM and p53 through the
accumulation of genotoxic levels of DNA damage. Moreover, USP7 inhibition
sensitized p53-defective, chemotherapy-resistant CLL cells to clinically
achievable doses of HRR-inducing chemotherapeutic agents in vitro and in vivo in
a murine xenograft model. Together, these results identify USP7 as a promising
therapeutic target for the treatment of hematological malignancies with DDR
defects, where ATM/p53-dependent apoptosis is compromised.
PMID- 28495794
TI - An endpoint associated with clinical benefit after initial treatment of chronic
graft-versus-host disease.
AB - No gold standard has been established as a primary endpoint in trials of initial
treatment of chronic graft-versus-host disease (GVHD), and evidence showing the
association of any proposed primary endpoint with clinical benefit has not been
conclusively demonstrated. To address this gap, we analyzed outcomes in a cohort
of 328 patients enrolled in a prospective, multicenter, observational study
within 3 months after diagnosis of chronic GVHD. Complete and partial response,
stable disease, and progressive disease were defined according to the 2014
National Institutes of Health Consensus Development Conference on Criteria for
Clinical Trials in Chronic Graft-Versus-Host Disease. Success was defined as
complete or partial response with no secondary systemic treatment or recurrent
malignancy at 1 year after enrollment. Success was observed in fewer than 20% of
the patients. The burden of disease manifestations at 1 year was lower for
patients in this category than for those with stable or progressive disease.
Systemic treatment ended earlier, and subsequent mortality was lower among
patients with complete or partial response than among those with stable or
progressive disease and those who had received secondary systemic treatment. We
conclude that survival with a complete or partial response and no previous
secondary systemic treatment or recurrent malignancy at 1 year after initial
systemic therapy is associated with clinical benefit, a critical characteristic
for consideration as a primary endpoint in a pivotal clinical trial. This
prospective observational study was registered at www.clinicaltrials.gov as
#NCT00637689.
PMID- 28495795
TI - The desmoplakin-intermediate filament linkage regulates cell mechanics.
AB - The translation of mechanical forces into biochemical signals plays a central
role in guiding normal physiological processes during tissue development and
homeostasis. Interfering with this process contributes to cardiovascular disease,
cancer progression, and inherited disorders. The actin-based cytoskeleton and its
associated adherens junctions are well-established contributors to mechanosensing
and transduction machinery; however, the role of the desmosome-intermediate
filament (DSM-IF) network is poorly understood in this context. Because a force
balance among different cytoskeletal systems is important to maintain normal
tissue function, knowing the relative contributions of these structurally
integrated systems to cell mechanics is critical. Here we modulated the
interaction between DSMs and IFs using mutant forms of desmoplakin, the protein
bridging these structures. Using micropillar arrays and atomic force microscopy,
we demonstrate that strengthening the DSM-IF interaction increases cell-substrate
and cell-cell forces and cell stiffness both in cell pairs and sheets of cells.
In contrast, disrupting the interaction leads to a decrease in these forces.
These alterations in cell mechanics are abrogated when the actin cytoskeleton is
dismantled. These data suggest that the tissue-specific variability in DSM-IF
network composition provides an opportunity to differentially regulate tissue
mechanics by balancing and tuning forces among cytoskeletal systems.
PMID- 28495796
TI - Phosphorylation of NHE3-S719 regulates NHE3 activity through the formation of
multiple signaling complexes.
AB - Casein kinase 2 (CK2) binds to the NHE3 C-terminus and constitutively
phosphorylates a downstream site (S719) that accounts for 40% of basal NHE3
activity. The role of CK2 in regulation of NHE3 activity in polarized Caco-2/bbe
cells was further examined by mutation of NHE3-S719 to A (not phosphorylated) or
D (phosphomimetic). NHE3-S719A but not -S719D had multiple changes in NHE3
activity: 1) reduced basal NHE3 activity-specifically, inhibition of the PI3K/AKT
dependent component; 2) reduced acute stimulation of NHE3 activity by LPA/LPA5R
stimulation; and 3) reduced acute inhibition of NHE3 activity-specifically,
elevated Ca2+ related (carbachol/Ca2+ ionophore), but there was normal inhibition
by forskolin and hyperosmolarity. The S719A mutant had reduced NHE3 complex size,
reduced expression in lipid rafts, increased BB mobile fraction, and reduced
binding to multiple proteins that bind throughout the NHE3 intracellular C
terminus, including calcineurin homologous protein, the NHERF family and SNX27
(related PDZ domains). These studies show that phosphorylation of the NHE3 at a
single amino acid in the distal part of the C-terminus affects multiple aspects
of NHE3 complex formation and changes the NHE3 lipid raft distribution, which
cause changes in specific aspects of basal as well as acutely stimulated and
inhibited Na+/H+ exchange activity.
PMID- 28495798
TI - A role for Sar1 and ARF1 GTPases during Golgi biogenesis in the protozoan
parasite Trypanosoma brucei.
AB - A single Golgi stack is duplicated and partitioned into two daughter cells during
the cell cycle of the protozoan parasite Trypanosoma brucei The source of
components required to generate the new Golgi and the mechanism by which it forms
are poorly understood. Using photoactivatable GFP, we show that the existing
Golgi supplies components directly to the newly forming Golgi in both intact and
semipermeabilized cells. The movement of a putative glycosyltransferase, GntB,
requires the Sar1 and ARF1 GTPases in intact cells. In addition, we show that
transfer of GntB from the existing Golgi to the new Golgi can be recapitulated in
semipermeabilized cells and is sensitive to the GTP analogue GTPgammaS. We
suggest that the existing Golgi is a key source of components required to form
the new Golgi and that this process is regulated by small GTPases.
PMID- 28495797
TI - Ixazomib enhances parathyroid hormone-induced beta-catenin/T-cell factor
signaling by dissociating beta-catenin from the parathyroid hormone receptor.
AB - The anabolic action of PTH in bone is mostly mediated by cAMP/PKA and Wnt
independent activation of beta-catenin/T-cell factor (TCF) signaling. beta
Catenin switches the PTH receptor (PTHR) signaling from cAMP/PKA to PLC/PKC
activation by binding to the PTHR. Ixazomib (Izb) was recently approved as the
first orally administered proteasome inhibitor for the treatment of multiple
myeloma; it acts in part by inhibition of pathological bone destruction.
Proteasome inhibitors were reported to stabilize beta-catenin by the ubiquitin
proteasome pathway. However, how Izb affects PTHR activation to regulate beta
catenin/TCF signaling is poorly understood. In the present study, using
CRISPR/Cas9 genome-editing technology, we show that Izb reverses beta-catenin
mediated PTHR signaling switch and enhances PTH-induced cAMP generation and cAMP
response element-luciferase activity in osteoblasts. Izb increases active forms
of beta-catenin and promotes beta-catenin translocation, thereby dissociating
beta-catenin from the PTHR at the plasma membrane. Furthermore, Izb facilitates
PTH-stimulated GSK3beta phosphorylation and beta-catenin phosphorylation. Thus
Izb enhances PTH stimulation of beta-catenin/TCF signaling via cAMP-dependent
activation, and this effect is due to its separating beta-catenin from the PTHR.
These findings provide evidence that Izb may be used to improve the therapeutic
efficacy of PTH for the treatment of osteoporosis and other resorptive bone
diseases.
PMID- 28495799
TI - Truncating mutations of SPAST associated with hereditary spastic paraplegia
indicate greater accumulation and toxicity of the M1 isoform of spastin.
AB - The SPAST gene, which produces two isoforms (M1 and M87) of the microtubule
severing protein spastin, is the chief gene mutated in hereditary spastic
paraplegia. Haploinsufficiency is a popular explanation for the disease, in part
because most of the >200 pathogenic mutations of the gene are truncating and
expected to produce only vanishingly small amounts of shortened proteins. Here we
studied two such mutations, N184X and S245X, and our results suggest another
possibility. We found that the truncated M1 proteins can accumulate to notably
higher levels than their truncated M87 or wild-type counterparts. Reminiscent of
our earlier studies on a pathogenic mutation that generates full-length M1 and
M87 proteins, truncated M1 was notably more detrimental to neurite outgrowth than
truncated M87, and this was true for both N184X and S245X. The greater toxicity
and tendency to accumulate suggest that, over time, truncated M1 could damage the
corticospinal tracts of human patients. Curiously, the N184X mutation triggers
the reinitiation of translation at a third start codon in SPAST, resulting in
synthesis of a novel M187 spastin isoform that is able to sever microtubules.
Thus microtubule severing may not be as reduced as previously assumed in the case
of that mutation.
PMID- 28495800
TI - Mechanically patterned neuromuscular junctions-in-a-dish have improved functional
maturation.
AB - Motor neuron (MN) diseases are progressive disorders resulting from degeneration
of neuromuscular junctions (NMJs), which form the connection between MNs and
muscle fibers. NMJ-in-a-dish models have been developed to examine human MN
associated dysfunction with disease; however such coculture models have randomly
oriented myotubes with immature synapses that contract asynchronously.
Mechanically patterned (MP) extracellular matrix with alternating soft and stiff
stripes improves current NMJ-in-a-dish models by inducing both mouse and human
myoblast durotaxis to stripes where they aligned, differentiated, and fused into
patterned myotubes. Compared to conventional culture on rigid substrates or
unpatterned hydrogels, MP substrates supported increased differentiation and
fusion, significantly larger acetylcholine (ACh) receptor clusters, and increased
expression of MuSK and Lrp4, two cell surface receptors required for NMJ
formation. Robust contractions were observed when mouse myotubes were stimulated
by ACh, with twitch duration and frequency most closely resembling those for
mature muscle on MP substrates. Fused myotubes, when cocultured with MNs, were
able to form even larger NMJs. Thus MP matrices produce more functionally active
NMJs-in-a-dish, which could be used to elucidate disease pathology and facilitate
drug discovery.
PMID- 28495802
TI - A common NHE3 single-nucleotide polymorphism has normal function and sensitivity
to regulatory ligands.
AB - Na+/H+ exchanger NHE3 mediates the majority of intestinal and renal
electroneutral sodium absorption. Dysfunction of NHE3 is associated with a
variety of diarrheal diseases. We previously reported that the NHE3 gene (SLC9A3)
has more than 400 single-nucleotide polymorphisms (SNPs) but few nonsynonymous
polymorphisms. Among the latter, one polymorphism (rs2247114-G>A), which causes a
substitution from arginine to cysteine at amino acid position 799 (p.R799C), is
common in Asian populations. To improve our understanding of the population
distribution and potential clinical significance of the NHE3-799C variant, we
investigated the frequency of this polymorphism in different ethnic groups using
bioinformatics analyses and in a cohort of Japanese patients with cardiovascular
or renal disease. We also characterized the function of human NHE3-799C and its
sensitivity to regulatory ligands in an in vitro model. NHE3-799C had an allele
frequency of 29.5-57.6% in Asian populations, 11.1-23.6% in European populations,
and 10.2-22.7% in African populations. PS120/FLAG-NHERF2 fibroblasts stably
expressing NHE3-799C had lower total protein expression but a higher percentage
of surface expression than those expressing NHE3-799R. NHE3-799C had similar
basal activity to NHE3-799R and was similarly stimulated or inhibited, by serum
or forskolin, respectively. Tenapanor, a small-molecule NHE3 inhibitor, dose
dependently inhibited NHE3-799R and NHE3-799C activities. The IC50 values of
tenapanor for NHE3-799C and NHE3-799R were significantly different, but both were
in the nanomolar range. These results suggest that NHE3-799C is a common variant
enriched in Asian populations, is not associated with compromised function or
abnormal regulation, and is unlikely to contribute to clinical disease.NEW &
NOTEWORTHY This study reports results on the functional significance of human
NHE3-799C under basal conditions and in response to regulatory ligands, including
a novel NHE3 inhibitor called tenapanor. We demonstrate that NHE3-799C is a
common variant of NHE3 that is enriched in Asian populations; however, in
contrast to our previous studies using rabbit NHE3, its presence seems to have
limited clinical significance in humans and is not associated with compromised
function or abnormal transport regulation.
PMID- 28495805
TI - Hans Tol #PromiseAndDeliver #ToughBrainyStraightforward.
PMID- 28495804
TI - Sham surgery versus labral repair or biceps tenodesis for type II SLAP lesions of
the shoulder: a three-armed randomised clinical trial.
AB - BACKGROUND: Labral repair and biceps tenodesis are routine operations for
superior labrum anterior posterior (SLAP) lesion of the shoulder, but evidence of
their efficacy is lacking. We evaluated the effect of labral repair, biceps
tenodesis and sham surgery on SLAP lesions. METHODS: A double-blind, sham
controlled trial was conducted with 118 surgical candidates (mean age 40 years),
with patient history, clinical symptoms and MRI arthrography indicating an
isolated type II SLAP lesion. Patients were randomly assigned to either labral
repair (n=40), biceps tenodesis (n=39) or sham surgery (n=39) if arthroscopy
revealed an isolated SLAP II lesion. Primary outcomes at 6 and 24 months were
clinical Rowe score ranging from 0 to 100 (best possible) and Western Ontario
Shoulder Instability Index (WOSI) ranging from 0 (best possible) to 2100.
Secondary outcomes were Oxford Instability Shoulder Score, change in main
symptoms, EuroQol (EQ-5D and EQ-VAS), patient satisfaction and complications.
RESULTS: There were no significant between-group differences at any follow-up in
any outcome. Between-group differences in Rowe scores at 2 years were: biceps
tenodesis versus labral repair: 1.0 (95% CI -5.4 to 7.4), p=0.76; biceps
tenodesis versus sham surgery: 1.6 (95% CI -5.0 to 8.1), p=0.64; and labral
repair versus sham surgery: 0.6 (95% CI -5.9 to 7.0), p=0.86. Similar results-no
differences between groups-were found for WOSI scores. Postoperative stiffness
occurred in five patients after labral repair and in four patients after
tenodesis. CONCLUSION: Neither labral repair nor biceps tenodesis had any
significant clinical benefit over sham surgery for patients with SLAP II lesions
in the population studied. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov
identifier: NCT00586742.
PMID- 28495806
TI - Infographic: Athlete monitoring in sport-top tips.
PMID- 28495807
TI - Neurologic Serious Adverse Events Associated with Nivolumab Plus Ipilimumab or
Nivolumab Alone in Advanced Melanoma, Including a Case Series of Encephalitis.
AB - BACKGROUND: Despite unprecedented efficacy across multiple tumor types, immune
checkpoint inhibitor therapy is associated with a unique and wide spectrum of
immune-related adverse events (irAEs), including neurologic events ranging from
mild headache to potentially life-threatening encephalitis. Here, we summarize
neurologic irAEs associated with nivolumab and ipilimumab melanoma treatment,
present cases of treatment-related encephalitis, and provide practical guidance
on diagnosis and management. METHODS: We searched a Global Pharmacovigilance and
Epidemiology database for neurologic irAEs reported over an 8-year period in
patients with advanced melanoma receiving nivolumab with or without ipilimumab
from 12 studies sponsored by Bristol-Myers Squibb. Serious neurologic irAEs were
reviewed, and relationship to nivolumab or ipilimumab was assigned. RESULTS: In
our search of 3,763 patients, 35 patients (0.93%) presented with 43 serious
neurologic irAEs, including neuropathy (n = 22), noninfective meningitis (n = 5),
encephalitis (n = 6), neuromuscular disorders (n = 3), and nonspecific adverse
events (n = 7). Study drug was discontinued (n = 20), interrupted (n = 8), or
unchanged (n = 7). Most neurologic irAEs resolved (26/35 patients; 75%). Overall,
median time to onset was 45 days (range 1-170) and to resolution was 32 days (2
809+). Median time to onset of encephalitis was 55.5 days (range 18-297); four
cases resolved and one was fatal. CONCLUSION: Both oncologists and neurologists
need to be aware of signs and symptoms of serious but uncommon neurologic irAEs
associated with checkpoint inhibitors. Prompt diagnosis and management using an
established algorithm are critical to minimize serious complications from these
neurologic irAEs. IMPLICATIONS FOR PRACTICE: With increasing use of checkpoint
inhibitors in cancer, practicing oncologists need to be aware of the potential
risk of neurologic immune-related adverse events and be able to provide prompt
treatment of this uncommon, but potentially serious, class of adverse events. We
summarize neurologic adverse events related to nivolumab alone or in combination
with ipilimumab in patients with advanced melanoma from 12 studies and examine in
depth 6 cases of encephalitis. We also provide input and guidance on the existing
neurologic adverse events management algorithm for nivolumab and ipilimumab.
PMID- 28495808
TI - Comprehensive Genomic Profiling of Esthesioneuroblastoma Reveals Additional
Treatment Options.
AB - BACKGROUND: Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma,
is a rare malignant neoplasm of the olfactory mucosa. Despite surgical resection
combined with radiotherapy and adjuvant chemotherapy, ENB often relapses with
rapid progression. Current multimodality, nontargeted therapy for relapsed ENB is
of limited clinical benefit. MATERIALS AND METHODS: We queried whether
comprehensive genomic profiling (CGP) of relapsed or refractory ENB can uncover
genomic alterations (GA) that could identify potential targeted therapies for
these patients. CGP was performed on formalin-fixed, paraffin-embedded sections
from 41 consecutive clinical cases of ENBs using a hybrid-capture, adaptor
ligation based next-generation sequencing assay to a mean coverage depth of 593X.
The results were analyzed for base substitutions, insertions and deletions,
select rearrangements, and copy number changes (amplifications and homozygous
deletions). RESULTS: Clinically relevant GA (CRGA) were defined as GA linked to
drugs on the market or under evaluation in clinical trials. A total of 28 ENBs
harbored GA, with a mean of 1.5 GA per sample. Approximately half of the ENBs
(21, 51%) featured at least one CRGA, with an average of 1 CRGA per sample. The
most commonly altered gene was TP53 (17%), with GA in PIK3CA, NF1, CDKN2A, and
CDKN2C occurring in 7% of samples. CONCLUSION: We report comprehensive genomic
profiles for 41 ENB tumors. CGP revealed potential new therapeutic targets,
including targetable GA in the mTOR, CDK and growth factor signaling pathways,
highlighting the clinical value of genomic profiling in ENB. IMPLICATIONS FOR
PRACTICE: Comprehensive genomic profiling of 41 relapsed or refractory ENBs
reveals recurrent alterations or classes of mutation, including amplification of
tyrosine kinases encoded on chromosome 5q and mutations affecting genes in the
mTOR/PI3K pathway. Approximately half of the ENBs (21, 51%) featured at least one
clinically relevant genomic alteration (CRGA), with an average of 1 CRGA per
sample. The most commonly altered gene was TP53 (17%), and alterations in PIK3CA,
NF1, CDKN2A, or CDKN2C were identified in 7% of samples. Responses to treatment
with the kinase inhibitors sunitinib, everolimus, and pazopanib are presented in
conjunction with tumor genomics.
PMID- 28495810
TI - Management of lipid-lowering therapy in patients with cardiovascular events in
the UK: a retrospective cohort study.
AB - OBJECTIVES: To describe low-density lipoprotein (LDL) cholesterol management and
lipid-lowering treatment patterns in patients with a cardiovascular (CV) event.
DESIGN: Retrospective cohort study using Clinical Practice Research Datalink
records linked with Hospital Episode Statistics data. SETTING: Routine clinical
practice in the UK from 2006 to 2012. PARTICIPANTS: Individuals >=18 years were
selected at their first CV-related hospitalisation (first event cohort) if they
had received >=2 lipid-lowering therapy prescriptions within 180 days beforehand.
Patients were stratified into four mutually exclusive subgroups based on the
presence or absence of vascular disease and of diabetes. Those with a second CV
hospitalisation within 36 months were included in a separate cohort (second event
cohort). PRIMARY AND SECONDARY OUTCOME MEASURES: LDL levels in the year prior to
the CV event and 12 months later as well as measures of adherence to lipid
lowering therapy during the 12 months after the CV hospitalisation. RESULTS:
There were 24 093 patients in the first event cohort, of whom 5274 were included
in the second event cohort. Most received moderate intensity statins at baseline
and 12 months. Among the four first event cohort subgroups at baseline, the
proportions with an LDL of <1.8 mmol/L was similar between the two diabetic
cohorts (36% to 38%) and were higher than those in the two non-diabetic cohorts
(17% to 22%) and in the second event cohort (31%). An incremental 5% to 9% had an
LDL below 1.8 mmol/L at 12 months, suggesting intensification of therapy. The
proportion of adherent patients (medication possession ratio of>=0.8) was highest
for statins, ranging from 68% to 72%. For ezetimibe, the range was 65% to 70%,
and for fibrates, it was 48% to 62%. CONCLUSIONS: Despite the existence of
effective therapies for lowering cholesterol, patients do not reach achievable
LDL targets.
PMID- 28495809
TI - Comparison of enteral versus intravenous potassium supplementation in
hypokalaemia in paediatric patients in intensive care post cardiac surgery: open
label randomised equivalence trial (EIPS).
AB - OBJECTIVES: The primary objective was to compare the efficacy of enteral
potassium replacement (EPR) and intravenous potassium replacement (IVPR) as first
line therapy. Secondary objectives included comparison of adverse effects and
number of doses required to resolve the episode of hypokalaemia. TRIAL DESIGN:
The EIPS trial is designed as a randomised, equivalence trial between two
treatment arms. STUDY SETTING: The study was conducted at the paediatric cardiac
intensive care unit (PCICU) at Aga Khan University Hospital, Karachi.
PARTICIPANTS: 41 patients (aged 1 month to 15 years) who were admitted to PCICU
post cardiac surgery were recruited (23 IVPR arm and 18 EPR arm). INTERVENTION:
Intervention arms were block randomised on alternate weeks for IVPR and EPR.
OUTCOME MEASURE: Change in serum potassium levels in (mmol/L) and percentage
change after each event of potassium replacement by the intravenous or enteral
route. RESULTS: Both groups (41 patients) had similar baseline characteristics.
Mean age was 4.7 (SD+/-4) years while the most common surgical procedure was
ventricular septal defect repair (12 patients, 29.3%). No mortality was observed
in either arm. Four episodes of vomiting and one arrhythmia were seen in the EPR
group. After adjusting for age, potassium level at the beginning of the episode,
average urine output, inotropic score and diuretic dose, it was found that there
was no statistically significant difference in change in potassium levels after
EPR and IVPR: 0.86 mmol/L (+/-0.8) and 0.82 mmol/L (+/-0.7) respectively (p=0.86,
95% CI -0.08 to 1.10), or percentage change in potassium level after enteral and
intravenous replacement: 26% (+/-30) and 24% (+/-20) (95% CI -3.42 to 4.03,
p=0.87). CONCLUSION: EPR may be an equally efficacious alternative first-line
therapy in treating hypokalaemia after surgery in selective patients with
congenital heart disease. ETHICS AND DISSEMINATION: This study has been approved
by Ethics Review Committee at AKU. TRIAL REGISTRATION NUMBER: NCT02015962.
PMID- 28495811
TI - Randomised controlled trial of online continuing education for health
professionals to improve the management of chronic fatigue syndrome: a study
protocol.
AB - INTRODUCTION: Chronic fatigue syndrome (CFS) is a serious and debilitating
illness that affects between 0.2%-2.6% of the world's population. Although there
is level 1 evidence of the benefit of cognitive behaviour therapy (CBT) and
graded exercise therapy (GET) for some people with CFS, uptake of these
interventions is low or at best untimely. This can be partly attributed to poor
clinician awareness and knowledge of CFS and related CBT and GET interventions.
This trial aims to evaluate the effect of participation in an online education
programme, compared with a wait-list control group, on allied health
professionals' knowledge about evidence-based CFS interventions and their levels
of confidence to engage in the dissemination of these interventions. METHODS AND
ANALYSIS: A randomised controlled trial consisting of 180 consenting allied
health professionals will be conducted. Participants will be randomised into an
intervention group (n=90) that will receive access to the online education
programme, or a wait-list control group (n=90). The primary outcomes will be: 1)
knowledge and clinical reasoning skills regarding CFS and its management,
measured at baseline, postintervention and follow-up, and 2) self-reported
confidence in knowledge and clinical reasoning skills related to CFS. Secondary
outcomes include retention of knowledge and satisfaction with the online
education programme. The influence of the education programme on clinical
practice behaviour, and self-reported success in the management of people with
CFS, will also be assessed in a cohort study design with participants from the
intervention and control groups combined. ETHICS AND DISSEMINATION: The study
protocol has been approved by the Human Research Ethics Committee at The
University of New South Wales (approval number HC16419). Results will be
disseminated via peer-reviewed journal articles and presentations at scientific
conferences and meetings. TRIAL REGISTRATION: ACTRN12616000296437.
PMID- 28495803
TI - On the Run for Hippocampal Plasticity.
AB - Accumulating research in rodents and humans indicates that exercise benefits
brain function and may prevent or delay onset of neurodegenerative conditions. In
particular, exercise modifies the structure and function of the hippocampus, a
brain area important for learning and memory. This review addresses the central
and peripheral mechanisms underlying the beneficial effects of exercise on the
hippocampus. We focus on running-induced changes in adult hippocampal
neurogenesis, neural circuitry, neurotrophins, synaptic plasticity,
neurotransmitters, and vasculature. The role of peripheral factors in hippocampal
plasticity is also highlighted. We discuss recent evidence that systemic factors
released from peripheral organs such as muscle (myokines), liver (hepatokines),
and adipose tissue (adipokines) during exercise contribute to hippocampal
neurotrophin and neurogenesis levels, and memory function. A comprehensive
understanding of the body-brain axis is needed to elucidate how exercise improves
hippocampal plasticity and cognition.
PMID- 28495812
TI - Value of pulmonary artery pressure in predicting in-hospital and one-year
mortality after valve replacement surgery in middle-aged and aged patients with
rheumatic mitral disease: an observational study.
AB - OBJECTIVES: To investigate the role of pulmonary artery pressure (PAP) in
predicting in-hospital death after valve replacement surgery in middle-aged and
aged patients with rheumatic mitral disease. DESIGN: An observational study.
SETTING: Guangdong General Hospital, China. PARTICIPANTS: 1639middle-aged and
aged patients (mean age 57+/-6 years) diagnosed with rheumatic mitral disease,
undergoing valve replacement surgery and receiving coronary angiography and
transthoracic echocardiography before operation, were enrolled. INTERVENTIONS:
All participants underwent valve replacement surgery and received coronary
angiography before operation. PRIMARY AND SECONDARY OUTCOME MEASURES: In-hospital
death and 1-year mortality after operation. METHODS: Included patients were
divided into four groups based on the preoperative PAP obtained by
echocardiography: group A (PAP<=30 mm Hg); group B (>30 mm Hg50 mm Hg70 mm Hg). The relationship
between PAP and in-hospital death and cumulative rate of 1-year mortality was
evaluated. RESULTS: In-hospital mortality rate increased gradually but
significantly as the PAP level increased, with 1.9% in group A (n=268), 2.3% in
group B (n=771), 4.7% in group C (n=384) and 10.2% in group D (n=216) (p<0.001).
Multivariate analysis showed that PAP>70 mm Hg was an independent predictor of in
hospital death (OR=2.93, 95% CI 1.61 to 5.32, p<0.001). PAP>52.5 mm Hg had a
sensitivity of 60.3% and specificity of 67.7% in predicting in-hospital death
(area under the curve=0.672, 95% CI 0.602 to 0.743, p<0.001). Kaplan-Meier
analysis showed that patients with PAP>52.5 mm Hg had higher 1-year mortality
after operation than those without (log-rank=21.51, p<0.001). CONCLUSIONS: PAP
could serve as a predictor of postoperative in-hospital and 1-year mortality
after valve replacement surgery in middle-aged and aged patients with rheumatic
mitral disease.
PMID- 28495813
TI - Trends in the supply of California's emergency departments and inpatient
services, 2005-2014: a retrospective analysis.
AB - OBJECTIVES: Given increasing demand for emergency care, there is growing concern
over the availability of emergency department (ED) and inpatient resources.
Existing studies of ED bed supply are dated and often overlook hospital capacity
beyond ED settings. We described recent statewide trends in the capacity of ED
and inpatient hospital services from 2005 to 2014. DESIGN: Retrospective
analysis. SETTING: Using California hospital data, we examined the absolute and
per admission changes in ED beds and inpatient beds in all hospitals from 2005 to
2014. PARTICIPANTS: Our sample consisted of all patients inpatient and
outpatient) from 501 hospital facilities over 10-year period. OUTCOME MEASURES:
We analysed linear trends in the total annual ED visits, ED beds, licensed and
staffed inpatient hospital beds and bed types, ED beds per ED visit, and
inpatient beds per admission (ED and non-ED). RESULTS: Between 2005 and 2014, ED
visits increased from 9.8 million to 13.2 million (an increase of 35.0%,
p<0.001). ED beds also increased (by 29.8%, p<0.001), with an average annual
increase of 195.4 beds. Despite this growth, ED beds per visit decreased by 3.9%,
from 6.0 ED beds per 10 000 ED visits in 2005 to 5.8 beds in 2014 (p=0.01). While
overall admission numbers declined by 4.9% (p=0.06), inpatient medical/surgical
beds per visit grew by 11.3%, from 11.6 medical/surgical beds per 1000 admissions
in 2005 to 12.9 beds in 2014 (p<0.001). However, there were reductions in
psychiatric and chemical dependency beds per admission, by -15.3% (p<0.001) and
22.4% (p=0.05), respectively. CONCLUSIONS: These trends suggest that, in its
current state, inadequate supply of ED and specific inpatient beds cannot keep
pace with growing patient demand for acute care. Analysis of ED and inpatient
supply should capture dynamic variations in patient demand. Our novel 'beds
pervisit' metric offers improvements over traditional supply measures.
PMID- 28495814
TI - Automated control of mechanical ventilation during general anaesthesia: study
protocol of a bicentric observational study (AVAS).
AB - INTRODUCTION: Automated control of mechanical ventilation during general
anaesthesia is not common. A novel system for automated control of most of the
ventilator settings was designed and is available on an anaesthesia machine.
METHODS AND ANALYSIS: The 'Automated control of mechanical ventilation during
general anesthesia study' (AVAS) is an international investigator-initiated
bicentric observational study designed to examine safety and efficacy of the
system during general anaesthesia. The system controls mechanical breathing
frequency, inspiratory pressure, pressure support, inspiratory time and trigger
sensitivity with the aim to keep a patient stable in user adoptable target zones.
Adult patients, who are classified as American Society of Anesthesiologists
physical status I, II or III, scheduled for elective surgery of the upper or
lower limb or for peripheral vascular surgery in general anaesthesia without any
additional regional anaesthesia technique and who gave written consent for study
participation are eligible for study inclusion. Primary endpoint of the study is
the frequency of specifically defined adverse events. Secondary endpoints are
frequency of normoventilation, hypoventilation and hyperventilation, the time
period between switch from controlled ventilation to assisted ventilation,
achievement of stable assisted ventilation of the patient, proportion of time
within the target zone for tidal volume, end-tidal partial pressure of carbon
dioxide as individually set up for each patient by the user, frequency of alarms,
frequency distribution of tidal volume, inspiratory pressure, inspiration time,
expiration time, end-tidal partial pressure of carbon dioxide and the number of
re-intubations. ETHICS AND DISSEMINATION: AVAS will be the first clinical study
investigating a novel automated system for the control of mechanical ventilation
on an anaesthesia machine. The study was approved by the ethics committees of
both participating study sites. In case that safety and efficacy are acceptable,
a randomised controlled trial comparing the novel system with the usual practice
may be warranted. TRIAL REGISTRATION: DRKS DRKS00011025, registered 12 October
2016; clinicaltrials.gov ID. NCT02644005, registered 30 December 2015.
PMID- 28495815
TI - Understanding the implementation and adoption of an information technology
intervention to support medicine optimisation in primary care: qualitative study
using strong structuration theory.
AB - OBJECTIVES: Using strong structuration theory, we aimed to understand the
adoption and implementation of an electronic clinical audit and feedback tool to
support medicine optimisation for patients in primary care. DESIGN: This is a
qualitative study informed by strong structuration theory. The analysis was
thematic, using a template approach. An a priori set of thematic codes, based on
strong structuration theory, was developed from the literature and applied to the
transcripts. The coding template was then modified through successive readings of
the data. SETTING: Clinical commissioning group in the south of England.
PARTICIPANTS: Four focus groups and five semi-structured interviews were
conducted with 18 participants purposively sampled from a range of stakeholder
groups (general practitioners, pharmacists, patients and commissioners). RESULTS:
Using the system could lead to improved medication safety, but use was determined
by broad institutional contexts; by the perceptions, dispositions and skills of
users; and by the structures embedded within the technology. These included
perceptions of the system as new and requiring technical competence and skill;
the adoption of the system for information gathering; and interactions and
relationships that involved individual, shared or collective use. The dynamics
between these external, internal and technological structures affected the
adoption and implementation of the system. CONCLUSIONS: Successful implementation
of information technology interventions for medicine optimisation will depend on
a combination of the infrastructure within primary care, social structures
embedded in the technology and the conventions, norms and dispositions of those
utilising it. Future interventions, using electronic audit and feedback tools to
improve medication safety, should consider the complexity of the social and
organisational contexts and how internal and external structures can affect the
use of the technology in order to support effective implementation.
PMID- 28495816
TI - Determinants of treatment duration in the prevention of recurrent venous
thromboembolism: a protocol for a balanced vignette experiment.
AB - INTRODUCTION: Venous thromboembolism (VTE) is a condition that annually occurs in
approximately 10/00 of the world's population. Patients who have already had a
VTE are at elevated risk for a recurrent VTE. Recurrent events increase the risk
of long-term sequelae and can be fatal. Adequate secondary prophylaxis is thus
needed to prevent such events. Patients with VTE are often prone to bleeding, and
pharmacological prophylaxis exacerbates bleeding risk. Expert opinions on the
optimum duration of secondary prophylaxis in VTE still vary substantially. The
existence of treatment guidelines has not led to uniformity of VTE secondary
prophylaxis strategies, which means that physicians still adhere to individual
risk calculi in determining treatment duration. METHODS AND ANALYSIS: The aim of
this study is to establish what factors lie at the root of this variance in VTE
secondary prophylactic treatment strategies, and what risk factors are deemed of
particular importance in determining the perceived risks and benefits of variable
treatment durations. To do this, we created a survey based on a D-efficient and G
efficient balanced experimental vignette design. This protocol covers all aspects
of how this survey was set up and how it was implemented. The analysis of the
experimental data will be carried out using mixed-effects methods, which are
beneficial in scenarios with high interindividual variance and correlated (eg,
repeated-measures) responses. We propose the use of maximal random effects
structures insofar as possible. ETHICS AND DISSEMINATION: All data are de
identified, and any identifying characteristics of the respondents will not be
reported in a final manuscript or elsewhere. A paper describing the expert
interviews is currently under peer review. A manuscript that contains the
analysis of the results of the experiment described in this protocol is being
drafted, and will also be submitted to a peer-reviewed journal.
PMID- 28495817
TI - Estimating the prevalence, hospitalisation and mortality from type 2 diabetes
mellitus in Nigeria: a systematic review and meta-analysis.
AB - BACKGROUND: There is not yet a comprehensive evidence-based epidemiological
report on type 2 diabetes mellitus (T2DM) in Nigeria. We aimed to estimate
country-wide and zonal prevalence, hospitalisation and mortality rates of T2DM in
Nigeria. METHODS: We searched MEDLINE, EMBASE, Global Health, Africa Journals
Online (AJOL) and Google Scholar for population and hospital-based studies on
T2DM in Nigeria. We conducted a random-effects meta-analysis on extracted crude
estimates, and applied a meta-regression epidemiological model, using the United
Nations demographics for Nigeria in 1990 and 2015 to determine estimates of
diabetes in Nigeria for the two years. RESULTS: 42 studies, with a total
population of 91 320, met our selection criteria. Most of the studies selected
were of medium quality (90.5%). The age-adjusted prevalence rates of T2DM in
Nigeria among persons aged 20-79 years increased from 2.0% (95% CI 1.9% to 2.1%)
in 1990 to 5.7% (95% CI 5.5% to 5.8%) in 2015, accounting for over 874 000 and
4.7 million cases, respectively. The pooled prevalence rate of impaired glucose
tolerance was 10.0% (95% CI 4.5% to 15.6%), while impaired fasting glucose was
5.8% (95% CI 3.8% to 7.8%). Hospital admission rate for T2DM was 222.6 (95% CI
133.1 to 312.1) per 100 000 population with hyperglycaemic emergencies, diabetic
foot and cardiovascular diseases being most common complications. The overall
mortality rate was 30.2 (95% CI 14.6 to 45.8) per 100 000 population, with a case
fatality rate of 22.0% (95% CI 8.0% to 36.0%). CONCLUSION: Our findings suggest
an increasing burden of T2DM in Nigeria with many persons currently undiagnosed,
and few known cases on treatment.
PMID- 28495820
TI - Next government must tackle public health "ticking time bomb," says BMA.
PMID- 28495821
TI - How to Image Repaired Tetralogy of Fallot.
PMID- 28495818
TI - Application of minimal important differences in degenerative knee disease
outcomes: a systematic review and case study to inform BMJ Rapid Recommendations.
AB - OBJECTIVES: To identify the most credible anchor-based minimal important
differences (MIDs) for patient important outcomes in patients with degenerative
knee disease, and to inform BMJ Rapid Recommendations for arthroscopic surgery
versus conservative management DESIGN: Systematic review. OUTCOME MEASURES:
Estimates of anchor-based MIDs, and their credibility, for knee symptoms and
health-related quality of life (HRQoL). DATA SOURCES: MEDLINE, EMBASE and
PsycINFO. ELIGIBILITY CRITERIA: We included original studies documenting the
development of anchor-based MIDs for patient-reported outcomes (PROs) reported in
randomised controlled trials included in the linked systematic review and meta
analysis and judged by the parallel BMJ Rapid Recommendations panel as critically
important for informing their recommendation: measures of pain, function and
HRQoL. RESULTS: 13 studies reported 95 empirically estimated anchor-based MIDs
for 8 PRO instruments and/or their subdomains that measure knee pain, function or
HRQoL. All studies used a transition rating (global rating of change) as the
anchor to ascertain the MID. Among PROs with more than 1 estimated MID, we found
wide variation in MID values. Many studies suffered from serious methodological
limitations. We identified the following most credible MIDs: Western Ontario and
McMaster University Osteoarthritis Index (WOMAC; pain: 12, function: 13), Knee
injury and Osteoarthritis Outcome Score (KOOS; pain: 12, activities of daily
living: 8) and EuroQol five dimensions Questionnaire (EQ-5D; 0.15). CONCLUSIONS:
We were able to distinguish between more and less credible MID estimates and
provide best estimates for key instruments that informed evidence presentation in
the associated systematic review and judgements made by the Rapid Recommendation
panel. TRIAL REGISTRATION NUMBER: CRD42016047912.
PMID- 28495819
TI - Knee arthroscopy versus conservative management in patients with degenerative
knee disease: a systematic review.
AB - OBJECTIVE: To determine the effects and complications of arthroscopic surgery
compared with conservative management strategies in patients with degenerative
knee disease. DESIGN: Systematic review. MAIN OUTCOME MEASURES: Pain, function,
adverse events. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Central Register of
Controlled Trials (CENTRAL), Google Scholar and Open Grey up to August 2016.
ELIGIBILITY CRITERIA: For effects, randomised clinical trials (RCTs) comparing
arthroscopic surgery with a conservative management strategy (including sham
surgery) in patients with degenerative knee disease. For complications, RCTs and
observational studies. REVIEW METHODS: Two reviewers independently extracted data
and assessed risk of bias for patient-important outcomes. A parallel guideline
committee (BMJ Rapid Recommendations) provided input on the design and
interpretation of the systematic review, including selection of patient-important
outcomes. We used the GRADE approach to rate the certainty (quality) of the
evidence. RESULTS: We included 13 RCTs and 12 observational studies. With respect
to pain, the review identified high-certainty evidence that knee arthroscopy
results in a very small reduction in pain up to 3 months (mean difference =5.4 on
a 100-point scale, 95% CI 2.0 to 8.8) and very small or no pain reduction up to 2
years (mean difference =3.1, 95% CI -0.2 to 6.4) when compared with conservative
management. With respect to function, the review identified moderate-certainty
evidence that knee arthroscopy results in a very small improvement in the short
term (mean difference =4.9 on a 100-point scale, 95% CI 1.5 to 8.4) and very
small or no improved function up to 2 years (mean difference =3.2, 95% CI -0.5 to
6.8). Alternative presentations of magnitude of effect, and associated
sensitivity analyses, were consistent with the findings of the primary analysis.
Low-quality evidence suggested a very low probability of serious complications
after knee arthroscopy. CONCLUSIONS: Over the long term, patients who undergo
knee arthroscopy versus those who receive conservative management strategies do
not have important benefits in pain or function. TRIAL REGISTRATION NUMBER:
PROSPERO CRD42016046242.
PMID- 28495822
TI - How to Image Congenital Left Heart Obstruction in Adults.
PMID- 28495823
TI - How to Image the Adult Patient With Fontan Circulation.
PMID- 28495825
TI - Congenital Heart Disease: Multimodal Imaging Is Every Day's Routine.
PMID- 28495824
TI - How to Image the Dilated Right Ventricle.
PMID- 28495826
TI - Genetic Drivers of von Willebrand Factor Levels in an Ischemic Stroke Population
and Association With Risk for Recurrent Stroke.
AB - BACKGROUND AND PURPOSE: von Willebrand factor (vWF) plays an important role in
thrombus formation during cerebrovascular damage. We sought to investigate the
potential role of circulating vWF in recurrent cerebrovascular events and
identify genetic contributors to variation in vWF level in an ischemic stroke
population. METHODS: We analyzed the effect of circulating vWF on risk of
recurrent stroke using survival models in the VISP trial (Vitamin Intervention
for Stroke Prevention) and the use of vWF in reclassification over traditional
factors. We conducted a genome-wide association study) with imputation, based on
1000 Genomes Project data, for circulating vWF levels and then interrogated loci
previously associated with vWF levels. We performed expression quantitative trait
locus analysis for vWF across different tissues. RESULTS: Elevated vWF levels
were associated with increased risk for recurrent stroke in VISP. Adding vWF to
traditional clinical parameters also improved recurrent stroke risk prediction.
We identified single-nucleotide polymorphisms significantly associated with
circulating vWF at the ABO locus (P<5*10-8) and replicated findings from previous
genetic associations of vWF levels in humans. Expression quantitative trait locus
analyses demonstrate that most associated ABO single-nucleotide polymorphisms
were also associated with vWF gene expression. CONCLUSIONS: Elevated vWF levels
are associated with recurrent stroke in VISP. In the VISP population, genetic
determinants of vWF levels that impact vWF gene expression were identified. These
data add to our knowledge of the pathophysiologic and genetic basis for recurrent
stroke risk and may have implications for clinical care decision making.
PMID- 28495828
TI - Letter by McGowan Regarding Article, "Quality of Acute Care and Long-Term Quality
of Life and Survival: The Australian Stroke Clinical Registry".
PMID- 28495827
TI - Hyperbaric Oxygen Reduces Infarction Volume and Hemorrhagic Transformation
Through ATP/NAD+/Sirt1 Pathway in Hyperglycemic Middle Cerebral Artery Occlusion
Rats.
AB - BACKGROUND AND PURPOSE: Energy depletion is a critical factor leading to cell
death and brain dysfunction after ischemic stroke. In this study, we investigated
whether energy depletion is involved in hyperglycemia-induced hemorrhagic
transformation after ischemic stroke and determined the pathway underlying the
beneficial effects of hyperbaric oxygen (HBO). METHODS: After 2-hour middle
cerebral artery occlusion, hyperglycemia was induced by injecting 50% dextrose (6
mL/kg) intraperitoneally at the onset of reperfusion. Immediately after it, rats
were exposed to HBO at 2 atmospheres absolutes for 1 hour. ATP synthase inhibitor
oligomycin A, nicotinamide phosphoribosyl transferase inhibitor FK866, or silent
mating type information regulation 2 homolog 1 siRNA was administrated for
interventions. Infarct volume, hemorrhagic volume, and neurobehavioral deficits
were recorded; the level of blood glucose, ATP, and nicotinamide adenine
dinucleotide and the activity of nicotinamide phosphoribosyl transferase were
monitored; the expression of silent mating type information regulation 2 homolog
1, acetylated p53, acetylated nuclear factor-kappaB, and cleaved caspase 3 were
detected by Western blots; and the activity of matrix metalloproteinase-9 was
assayed by zymography. RESULTS: Hyperglycemia deteriorated energy metabolism and
reduced the level of ATP and nicotinamide adenine dinucleotide and exaggerated
hemorrhagic transformation, blood-brain barrier disruption, and neurological
deficits after middle cerebral artery occlusion. HBO treatment increased the
levels of the ATP and nicotinamide adenine dinucleotide and consequently
increased silent mating type information regulation 2 homolog 1, resulting in
attenuation of hemorrhagic transformation, brain infarction, as well as
improvement of neurological function in hyperglycemic middle cerebral artery
occlusion rats. CONCLUSIONS: HBO induced activation of ATP/nicotinamide adenine
dinucleotide/silent mating type information regulation 2 homolog 1 pathway and
protected blood-brain barrier in hyperglycemic middle cerebral artery occlusion
rats. HBO might be promising approach for treatment of acute ischemic stroke
patients, especially patients with diabetes mellitus or treated with r-tPA
(recombinant tissue-type plasminogen activator).
PMID- 28495829
TI - Association Between Brain-Derived Neurotrophic Factor Genotype and Upper
Extremity Motor Outcome After Stroke.
AB - BACKGROUND AND PURPOSE: The identification of intrinsic factors for predicting
upper extremity motor outcome could aid the design of individualized treatment
plans in stroke rehabilitation. The aim of this study was to identify prognostic
factors, including intrinsic genetic factors, for upper extremity motor outcome
in patients with subacute stroke. METHODS: A total of 97 patients with subacute
stroke were enrolled. Upper limb motor impairment was scored according to the
upper limb of Fugl-Meyer assessment score at 3 months after stroke. The
prediction of upper extremity motor outcome at 3 months was modeled using various
factors that could potentially influence this impairment, including patient
characteristics, baseline upper extremity motor impairment, functional and
structural integrity of the corticospinal tract, and brain-derived neurotrophic
factor genotype. Multivariate ordinal logistic regression models were used to
identify the significance of each factor. RESULTS: The independent predictors of
motor outcome at 3 months were baseline upper extremity motor impairment, age,
stroke type, and corticospinal tract functional integrity in all stroke patients.
However, in the group with severe motor impairment at baseline (upper limb score
of Fugl-Meyer assessment <25), the number of Met alleles in the brain-derived
neurotrophic factor genotype was also an independent predictor of upper extremity
motor outcome 3 months after stroke. CONCLUSIONS: Brain-derived neurotrophic
factor genotype may be a potentially useful predictor of upper extremity motor
outcome in patients with subacute stroke with severe baseline motor involvement.
PMID- 28495830
TI - Establishing Recommendations for Stroke Systems in the Thrombectomy Era: The
Upstate New York Stakeholder Proceedings.
AB - BACKGROUND AND PURPOSE: The American Heart Association/American Stroke
Association and Department of Health Stroke Coverdell Program convened a
stakeholder meeting in upstate NY to develop recommendations to enhance stroke
systems for acute large vessel occlusion. METHODS: Prehospital, hospital, and
Department of Health leadership were invited (n=157). Participants provided
goals/concerns and developed recommendations for prehospital triage and
interfacility transport, rating each using a 3-level impact (A [high], B, and C
[low]) and implementation feasibility (1 [high], 2, and 3 [low]) scale. Six weeks
later, participants finalized recommendations. RESULTS: Seventy-one stakeholders
(45% of invitees) attended. Six themes around goals/concerns emerged: (1)
emergency medical services capacity, (2) validated prehospital screening tools,
(3) facility capability, (4) triage/transport guidelines, (5) data
capture/feedback tools, and (6) facility competition. In response, high-impact
(level A) prehospital recommendations, stratified by implementation feasibility,
were (1) use of online medical control for triage (6%); (2) regional
transportation strategy (31%), standardized emergency medical services checklists
(18%), quality metrics (14%), standardized prehospital screening tools (13%), and
feedback for performance improvement (7%); and (3) smartphone application
algorithm for screening/decision-making (6%) and ambulance-based telemedicine
(6%). Level A interfacility transfer recommendations were (1) standardized
transfer process (32%)/timing goals (16%)/regionalized systems (11%), performance
metrics (11%), image sharing capabilities (7%); (2) provider education (9%) and
stroke toolbox (5%); and (3) interfacility telemedicine (7%) and feedback (2%).
CONCLUSIONS: The methods used and recommendations generated provide models for
stroke system enhancement. Implementation may vary based on geographic
need/capacity and be contingent on establishing standard care practices. Further
research is needed to establish optimal implementation strategies.
PMID- 28495833
TI - Dequalinium for bacterial vaginosis.
AB - Bacterial vaginosis is an infection characterised by overgrowth of anaerobic
bacteria in the vagina with an accompanying loss of lactobacilli, and is thought
to be the most common cause of abnormal vaginal discharge in women of child
bearing age.1 Standard treatment for symptomatic bacterial vaginosis consists of
a short course of an oral or topical antibiotic.2 Dequalinium, a topical
antiseptic agent, has been available for many years as a treatment for oral
infections.3 A new formulation, dequalinium 10mg vaginal tablets (Fluomizin-Kora
Healthcare), was licensed in the UK in June 2015 for the treatment of bacterial
vaginosis.4 Here, we review evidence for the effectiveness and safety of
dequalinium vaginal tablets in the management of bacterial vaginosis.
PMID- 28495831
TI - Clinical Correlates, Ethnic Differences, and Prognostic Implications of
Perivascular Spaces in Transient Ischemic Attack and Ischemic Stroke.
AB - BACKGROUND AND PURPOSE: Perivascular spaces (PVSs) are considered markers of
small vessel disease. However, their long-term prognostic implications in
transient ischemic attack/ischemic stroke patients are unknown. Ethnic
differences in PVS prevalence are also unknown. METHODS: Two independent
prospective studies were conducted, 1 comprising predominantly whites with
transient ischemic attack/ischemic stroke (OXVASC [Oxford Vascular] study) and 1
comprising predominantly Chinese with ischemic stroke (University of Hong Kong).
Clinical and imaging correlates, prognostic implications for stroke and death,
and ethnic differences in basal ganglia (BG) and centrum semiovale (CS) PVSs were
studied with adjustment for age, sex, vascular risk factors, and scanner
strength. RESULTS: Whites with transient ischemic attack/ischemic stroke (n=1028)
had a higher prevalence of both BG and CS-PVSs compared with Chinese (n=974; >20
BG-PVSs: 22.4% versus 7.1%; >20 CS-PVSs: 45.8% versus 10.4%; P<0.0001). More than
20 BG or CS-PVSs were both associated with increasing age and white matter
hyperintensity, although associations with BG-PVSs were stronger (all P<0.0001).
During 6924 patient-years of follow-up, BG-PVSs were also independently
associated with an increased risk of recurrent ischemic stroke (adjusted hazard
ratio compared with <11 PVSs, 11-20 PVSs: HR, 1.15; 95% confidence interval, 0.78
1.68; >20 PVSs: HR, 1.82; 1.18-2.80; P=0.011) but not intracerebral hemorrhage
(P=0.10) or all-cause mortality (P=0.16). CS-PVSs were not associated with
recurrent stroke (P=0.57) or mortality (P=0.072). Prognostic associations were
similar in both cohorts. CONCLUSIONS: Over and above ethnic differences in
frequency of PVSs in transient ischemic attack/ischemic stroke patients, BG and
CS-PVSs had similar risk factors, but although >20 BG-PVSs were associated with
an increased risk of recurrent ischemic stroke, CS-PVSs were not.
PMID- 28495834
TI - Testosterone therapy for menopausal women.
AB - It has been suggested that there is a link between low circulating concentrations
of testosterone and reduced sexual functioning in postmenopausal women,1 and it
has been more than 60 years since the effects of testosterone therapy for the
management of menopausal symptoms were first reported.2 Since then, testosterone
supplementation has received growing attention for its potential role in
maintaining sexual function in menopausal women. The National Institute for
Health and Care Excellence guideline on the diagnosis and management of menopause
recommends considering testosterone supplementation for women with low sexual
desire if hormone replacement therapy (HRT) alone has been ineffective.3 However,
in the UK no testosterone products are licensed for such use. A testosterone
patch authorised by the European Medicines Agency in 2006 for use in women with
surgical menopause was withdrawn from the market in 2012 for commercial reasons.4
Here, we provide an update on the evidence of the effectiveness and safety of
testosterone supplementation in menopausal women.
PMID- 28495835
TI - UK poverty has "devastating" effect on children's health, doctors warn.
PMID- 28495836
TI - Spatial regulation of organelle release from myosin V transport by p21-activated
kinases.
AB - Correct positioning of organelles is essential to eukaryotic cells. Molecular
motors transport organelles to their proper destinations, yet little is known
about the pathways that define these destinations. In Saccharomyces cerevisiae,
the myosin V motor Myo2 binds the vacuole-specific adapter Vac17 to attach to the
vacuole/lysosome and initiate transport. After arrival in the bud, Myo2 releases
the vacuole, and Vac17 is degraded. However, the mechanisms that spatially
regulate this release were not established. In this study, we report that the bud
cortex is a landmark that signals a successful delivery of the vacuole to the
bud. We demonstrate that upon arrival at the bud cortex, Vac17 is phosphorylated
by Cla4. Cla4-dependent phosphorylation is required for the ubiquitylation and
subsequent degradation of Vac17 and the release of the vacuole from Myo2. Our
study reveals a critical step in the spatial regulation of myosin V-dependent
organelle transport and may reveal common mechanisms for how molecular motors
accurately deposit cargoes at the correct locations.
PMID- 28495837
TI - Congressing kinetochores progressively load Ska complexes to prevent force
dependent detachment.
AB - Kinetochores mediate chromosome congression by either sliding along the lattice
of spindle microtubules or forming end-on attachments to their depolymerizing
plus-ends. By following the fates of individual kinetochores as they congress in
live cells, we reveal that the Ska complex is required for a distinct substep of
the depolymerization-coupled pulling mechanism. Ska depletion increases the
frequency of naturally occurring, force-dependent P kinetochore detachment
events, while being dispensable for the initial biorientation and movement of
chromosomes. In unperturbed cells, these release events are followed by
reattachment and successful congression, whereas in Ska-depleted cells, detached
kinetochores remain in a futile reattachment/detachment cycle that prevents
congression. We further find that Ska is progressively loaded onto bioriented
kinetochore pairs as they congress. We thus propose a model in which kinetochores
mature through Ska complex recruitment and that this is required for improved
load-bearing capacity and silencing of the spindle assembly checkpoint.
PMID- 28495839
TI - Medical residents' interest in and current status of Japanese postgraduate
education in acupuncture and moxibustion: a follow-up survey.
AB - BACKGROUND: Japanese traditional medicine (Kampo medicine) is an important
subject in Japanese medical schools. Acupuncture and moxibustion (AM), essential
categories of Kampo medicine, are taught in a few medical schools today. However,
the current state of postgraduate AM education is unknown. OBJECTIVE: To compare
medical residents' awareness of AM before their AM education in the 4th year of
medical school with that after completion of their 2-year postgraduate medical
residency. METHODS: We conducted a postal questionnaire survey of medical
residents at the end of their 2-year residency. We required a signature on this
questionnaire so that we could examine for changes in their awareness of AM with
those determined by similar, signed, former questionnaire surveys conducted
before and at the end of their 4th-year AM lectures in medical school (reported
previously). The completed questionnaires were returned by mail or facsimile.
RESULTS: Among 93 residents, there were 72 (77.4%) effective responses. Only
three residents (4%) had opportunities to learn AM during residency. Among the 68
residents who were not afforded the opportunity to do so, after completing their
two-year residency, 32(47%) stated that they would like to study AM. Interest in
AM was significantly less than that of the proportion of medical students (81%)
who were initially interested in AM when surveyed just before their fourth year
lectures on AM. CONCLUSIONS: Postgraduate AM education for medical residents
appears to be relatively scarce in Japan. Moreover, medical residents' levels of
interest in AM were lower than those demonstrated before their 4th-year AM
lectures in medical school.
PMID- 28495838
TI - Usher syndrome type 1-associated cadherins shape the photoreceptor outer segment.
AB - Usher syndrome type 1 (USH1) causes combined hearing and sight defects, but how
mutations in USH1 genes lead to retinal dystrophy in patients remains elusive.
The USH1 protein complex is associated with calyceal processes, which are
microvilli of unknown function surrounding the base of the photoreceptor outer
segment. We show that in Xenopus tropicalis, these processes are connected to the
outer-segment membrane by links composed of protocadherin-15 (USH1F protein).
Protocadherin-15 deficiency, obtained by a knockdown approach, leads to impaired
photoreceptor function and abnormally shaped photoreceptor outer segments. Rod
basal outer disks displayed excessive outgrowth, and cone outer segments were
curved, with lamellae of heterogeneous sizes, defects also observed upon
knockdown of Cdh23, encoding cadherin-23 (USH1D protein). The calyceal processes
were virtually absent in cones and displayed markedly reduced F-actin content in
rods, suggesting that protocadherin-15-containing links are essential for their
development and/or maintenance. We propose that calyceal processes, together with
their associated links, control the sizing of rod disks and cone lamellae
throughout their daily renewal.
PMID- 28495840
TI - Nonlinearities of heart rate variability in animal models of impaired cardiac
control: contribution of different time scales.
AB - Heart rate variability (HRV) has been extensively explored by traditional linear
approaches (e.g., spectral analysis); however, several studies have pointed to
the presence of nonlinear features in HRV, suggesting that linear tools might
fail to account for the complexity of the HRV dynamics. Even though the prevalent
notion is that HRV is nonlinear, the actual presence of nonlinear features is
rarely verified. In this study, the presence of nonlinear dynamics was checked as
a function of time scales in three experimental models of rats with different
impairment of the cardiac control: namely, rats with heart failure (HF),
spontaneously hypertensive rats (SHRs), and sinoaortic denervated (SAD) rats.
Multiscale entropy (MSE) and refined MSE (RMSE) were chosen as the discriminating
statistic for the surrogate test utilized to detect nonlinearity. Nonlinear
dynamics is less present in HF animals at both short and long time scales
compared with controls. A similar finding was found in SHR only at short time
scales. SAD increased the presence of nonlinear dynamics exclusively at short
time scales. Those findings suggest that a working baroreflex contributes to
linearize HRV and to reduce the likelihood to observe nonlinear components of the
cardiac control at short time scales. In addition, an increased sympathetic
modulation seems to be a source of nonlinear dynamics at long time scales.
Testing nonlinear dynamics as a function of the time scales can provide a
characterization of the cardiac control complementary to more traditional markers
in time, frequency, and information domains.NEW & NOTEWORTHY Although heart rate
variability (HRV) dynamics is widely assumed to be nonlinear, nonlinearity tests
are rarely used to check this hypothesis. By adopting multiscale entropy (MSE)
and refined MSE (RMSE) as the discriminating statistic for the nonlinearity test,
we show that nonlinear dynamics varies with time scale and the type of cardiac
dysfunction. Moreover, as complexity metrics and nonlinearities provide
complementary information, we strongly recommend using the test for nonlinearity
as an additional index to characterize HRV.
PMID- 28495841
TI - Lower-body negative pressure decreases noninvasively measured intracranial
pressure and internal jugular vein cross-sectional area during head-down tilt.
AB - Long-term spaceflight induces a near visual acuity change in ~50% of astronauts.
In some crew members, postflight cerebrospinal fluid (CSF) opening pressures by
lumbar puncture are as high as 20.9 mmHg; these members demonstrated optic disc
edema. CSF communicates through the cochlear aqueduct to affect perilymphatic
pressure and tympanic membrane motion. We hypothesized that 50 mmHg of lower-body
negative pressure (LBNP) during 15 degrees head-down tilt (HDT) would mitigate
elevations in internal jugular vein cross-sectional area (IJV CSA) and
intracranial pressure (ICP). Fifteen healthy adult volunteers were positioned in
sitting (5 min), supine (5 min), 15 degrees HDT (5 min), and 15 degrees HDT
with LBNP (10 min) postures for data collection. Evoked tympanic membrane
displacements (TMD) quantified ICP noninvasively. IJV CSA was measured using
standard ultrasound techniques. ICP and IJV CSA increased significantly from the
seated upright to the 15 degrees HDT posture (P < 0.05), and LBNP mitigated
these increases. LBNP at 25 mmHg reduced ICP during HDT (TMD of 322.13 +/- 419.17
nl) to 232.38 +/- 445.85 nl, and at 50 mmHg ICP was reduced further to TMD of
199.76 +/- 429.69 nl. In addition, 50 mmHg LBNP significantly reduced IJV CSA
(1.50 +/- 0.33 cm2) during 15 degrees HDT to 0.83 +/- 0.42 cm2 LBNP counteracts
the headward fluid shift elevation of ICP and IJV CSA experienced during
microgravity as simulated by15 degrees HDT. These data provide quantitative
evidence that LBNP shifts cephalic fluid to the lower body, reducing IJV CSA and
ICP.NEW & NOTEWORTHY The current study provides new evidence that 25 or 50 mmHg
of lower body negative pressure reduces jugular venous pooling and intracranial
pressure during simulated microgravity. Therefore, spaceflight countermeasures
that sequester fluid to the lower body may mitigate cephalic venous congestion
and vision impairment.
PMID- 28495844
TI - Molecular imaging of postprandial metabolism.
AB - Disordered postprandial metabolism of energy substrates is one of the main
defining features of prediabetes and contributes to the development of several
chronic diseases associated with obesity, such as type 2 diabetes and
cardiovascular diseases. Postprandial energy metabolism has been studied using
classical isotopic tracer approaches that are limited by poor access to
splanchnic metabolism and highly dynamic and complex exchanges of energy
substrates involving multiple organs and systems. Advances in noninvasive
molecular imaging modalities, such as PET and MRI/magnetic resonance spectroscopy
(MRS), have recently allowed important advances in our understanding of
postprandial energy metabolism in humans. The present review describes some of
these recent advances, with particular focus on glucose and fatty acid metabolism
in the postprandial state, and discusses current gaps in knowledge and new
perspectives of application of PET and MRI/MRS for the investigation and
treatment of human metabolic diseases.
PMID- 28495843
TI - Treating fructose-induced metabolic changes in mice with high-intensity interval
training: insights in the liver, white adipose tissue, and skeletal muscle.
AB - Fructose-rich caloric sweeteners induce adverse changes in the metabolism of
humans. The study evaluated the effects of high-intensity interval training
(HIIT) on a fructose feeding model, focusing on the liver, white adipose tissue
(WAT), skeletal muscle, and their interplay. Male C57BL/6 mice were fed for 18 wk
one of the following diets: control (C; 5% of total energy from fructose) or
fructose (F; 55% of total energy from fructose). In the 10th week, for an
additional 8-wk period, the groups were divided into nontrained (NT) or HIIT
groups, totaling four groups: C-NT, C-HIIT, F-NT, and F-HIIT. At the end of the
experiment, fructose consumption in the F-NT group led to a high systolic blood
pressure, high plasma triglycerides, insulin resistance with glucose intolerance,
and lower insulin sensitivity. We also observed liver steatosis, adipocyte
hypertrophy, and diminished gene expressions of peroxisome proliferator-activated
receptor-gamma coactivator 1-alpha and fibronectin type III domain containing 5
(FNDC5; irisin) in this F-NT group. These results were accompanied by decreased
gene expressions of nuclear respiratory factor 1 and mitochondrial transcription
factor A (markers of mitochondrial biogenesis), and peroxisome proliferator
activated receptor-alpha and carnitine palmitoyltransferase 1 (markers of beta
oxidation). HIIT improved all of these data in the C-HIIT and F-HIIT groups. In
conclusion, in mice fed a fructose diet, HIIT improved body mass, blood pressure,
glucose metabolism, and plasma triglycerides. Liver, WAT, and skeletal muscle
were positively modulated by HIIT, indicating HIIT as a coadjutant treatment for
diseases affecting these tissues.NEW & NOTEWORTHY We investigated the effects of
high-intensity interval training (HIIT) in mice fed a fructose-rich diet and the
resulting severe negative effect on the liver, white adipose tissue (WAT), and
skeletal muscle, which reduced the expression of fibronectin type III domain
containing 5 (FNDC5, irisin) and PGC1alpha and, consequently, affected markers of
mitochondrial biogenesis and beta-oxidation. Because HIIT may block these adverse
effects in all of these three tissues, it might be suggested that it functions as
a coadjutant treatment in combatting the alterations caused by high-fructose
intake.
PMID- 28495842
TI - The impact of ocular hemodynamics and intracranial pressure on intraocular
pressure during acute gravitational changes.
AB - Exposure to microgravity causes a bulk fluid shift toward the head, with
concomitant changes in blood volume/pressure, and intraocular pressure (IOP).
These and other factors, such as intracranial pressure (ICP) changes, are
suspected to be involved in the degradation of visual function and ocular
anatomical changes exhibited by some astronauts. This is a significant health
concern. Here, we describe a lumped-parameter numerical model to simulate
volume/pressure alterations in the eye during gravitational changes. The model
includes the effects of blood and aqueous humor dynamics, ICP, and IOP-dependent
ocular compliance. It is formulated as a series of coupled differential equations
and was validated against four existing data sets on parabolic flight, body
inversion, and head-down tilt (HDT). The model accurately predicted acute IOP
changes in parabolic flight and HDT, and was satisfactory for the more extreme
case of inversion. The short-term response to the changing gravitational field
was dominated by ocular blood pressures and compliance, while longer-term
responses were more dependent on aqueous humor dynamics. ICP had a negligible
effect on acute IOP changes. This relatively simple numerical model shows
promising predictive capability. To extend the model to more chronic conditions,
additional data on longer-term autoregulation of blood and aqueous humor dynamics
are needed.NEW & NOTEWORTHY A significant percentage of astronauts present
anatomical changes in the posterior eye tissues after spaceflight. Hypothesized
increases in ocular blood volume and intracranial pressure (ICP) in space have
been considered to be likely factors. In this work, we provide a novel numerical
model of the eye that incorporates ocular hemodynamics, gravitational forces, and
ICP changes. We find that changes in ocular hemodynamics govern the response of
intraocular pressure during acute gravitational change.
PMID- 28495845
TI - Edmund Goodwyn and the first description of diving bradycardia.
AB - Diving bradycardia is a primordial oxygen-conserving reflex by which the heart
rate of air-breathing vertebrates, including humans, slows down in response to
water immersion. Its discovery is attributed to Paul Bert, whose seminal
observation was published in 1870 as part of a series of experiments that
examined physiological adaptations to asphyxia in ducks and other animals.
However, Edmund Goodwyn, a British physician who studied medicine at the
University of Edinburgh, had already described this reflex in his doctoral
thesis, which was originally published in Latin in 1786 and again in English in
1788. Ironically, even though Goodwyn's work has yet to be recognized in the
diving physiology literature, it was referenced in the very publication that
contains Bert's original observation. Thus this article brings Goodwyn's work and
its historical context to light and argues that he should be credited with the
first description of diving bradycardia.
PMID- 28495846
TI - Dispelling the myth that habitual caffeine consumption influences the performance
response to acute caffeine supplementation.
AB - This study investigates the influence of habitual caffeine intake on aerobic
exercise-performance responses to acute caffeine supplementation. A double-blind,
crossover, counterbalanced study was performed. Forty male endurance-trained
cyclists were allocated into tertiles, according to their daily caffeine intake:
low (58 +/- 29 mg/d), moderate (143 +/- 25 mg/d), and high (351 +/- 139 mg/d)
consumers. Participants completed three trials in which they performed simulated
cycling time trials (TTs) in the fastest time possible following ingestion of the
following: caffeine (CAF: 6 mg/kg body mass), placebo (PLA), and no supplement
(CON). A mixed-model analysis revealed that TT performance was significantly
improved in CAF compared with PLA and CON (29.92 +/- 2.18 vs. 30.81 +/- 2.67 and
31.14 +/- 2.71 min, respectively; P = 0.0002). Analysis of covariance revealed no
influence of habitual caffeine intake as a covariate on exercise performance (P =
0.47). TT performance was not significantly different among tertiles (P = 0.75).
No correlation was observed between habitual caffeine intake and absolute changes
(CAF - CON) in TT performance with caffeine (P = 0.524). Individual analysis
showed that eight, seven, and five individuals improved above the variation of
the test in CAF in the low, moderate, and high tertiles, respectively. A Fisher's
exact test did not show any significant differences in the number of individuals
who improved in CAF among the tertiles (P > 0.05). Blood lactate and ratings of
perceived exertion were not different between trials and tertiles (P > 0.05).
Performance effects of acute caffeine supplementation during an ~30-min cycling
TT performance were not influenced by the level of habitual caffeine
consumption.NEW & NOTEWORTHY There has been a long-standing paradigm that
habitual caffeine intake may influence the ergogenicity of caffeine
supplementation. Low, moderate, and high caffeine consumers showed similar
absolute and relative improvements in cycling time-trial performance following
acute supplementation of 6 mg/kg body mass caffeine. Performance effects of acute
caffeine were not influenced by the level of habitual caffeine consumption,
suggesting that high habitual caffeine intake does not negate the benefits of
acute caffeine supplementation.
PMID- 28495847
TI - Inflammatory responses to acute elevations of carbon dioxide in mice.
AB - Health risks are described from elevated indoor air carbon dioxide (CO2), which
often ranges from 1,000 to 4,000 ppm, but the mechanisms are unknown. Here, we
demonstrate that mice exposed for 2 h to 2,000 or 4,000 ppm CO2 exhibit,
respectively, 3.4 +/- 0.9-fold (SE, n = 6) and 4.1 +/- 0.7-fold (n = 10)
elevations in circulating microparticles (MPs); neutrophil and platelet
activation, and vascular leak in brain, muscle, and distal colon. Interleukin
(IL)-1beta content of MPs also increases after 2,000 ppm by 3.8 +/- 0.6-fold (n =
6) and after 4,000 ppm CO2 by 9.3 +/- 1.1-fold (n = 10) greater than control. CO2
induced vascular damage is abrogated by treating mice with an antibody to IL
1beta or an IL-1beta receptor inhibitor. Injecting naive mice with CO2-induced
MPs expressing a protein found on mature neutrophils recapitulates vascular
damage as seen with elevated CO2, and destruction of MPs in CO2-exposed mice
abrogates vascular injuries without altering neutrophil or platelet activation.
We conclude that environmentally relevant elevations of CO2 trigger neutrophils
to generate MPs containing high concentrations of IL-1beta that cause diffuse
inflammatory vascular injury.NEW & NOTEWORTHY Elevated levels of CO2 are often
found in indoor air and cause adverse health effects, but the mechanisms have not
been identified. In a murine model, environmentally relevant levels of CO2 were
found to cause diffuse vascular damage because neutrophils are stimulated to
produce microparticles that contain high concentrations of interleukin-1beta.
PMID- 28495850
TI - A young man with elbow pain.
PMID- 28495848
TI - Physical activity modulates corticospinal excitability of the lower limb in young
and old adults.
AB - Aging is associated with reduced neuromuscular function, which may be due in part
to altered corticospinal excitability. Regular physical activity (PA) may
ameliorate these age-related declines, but the influence of PA on corticospinal
excitability is unknown. The purpose of this study was to determine the influence
of age, sex, and PA on corticospinal excitability by comparing the stimulus
response curves of motor evoked potentials (MEP) in 28 young (22.4 +/- 2.2 yr; 14
women and 14 men) and 50 old adults (70.2 +/- 6.1 yr; 22 women and 28 men) who
varied in activity levels. Transcranial magnetic stimulation was used to elicit
MEPs in the active vastus lateralis muscle (10% maximal voluntary contraction)
with 5% increments in stimulator intensity until the maximum MEP amplitude.
Stimulus-response curves of MEP amplitudes were fit with a four-parameter
sigmoidal curve and the maximal slope calculated (slopemax). Habitual PA was
assessed with tri-axial accelerometry and participants categorized into either
those meeting the recommended PA guidelines for optimal health benefits (>10,000
steps/day, high-PA; n = 21) or those not meeting the guidelines (<10,000
steps/day, low-PA; n = 41). The MEP amplitudes and slopemax were greater in the
low-PA compared with the high-PA group (P < 0.05). Neither age nor sex influenced
the stimulus-response curve parameters (P > 0.05), suggesting that habitual PA
influenced the excitability of the corticospinal tract projecting to the lower
limb similarly in both young and old adults. These findings provide evidence that
achieving the recommended PA guidelines for optimal health may mediate its
effects on the nervous system by decreasing corticospinal excitability.NEW &
NOTEWORTHY Transcranial magnetic stimulation was used to determine whether
achieving the recommended 10,000 steps/day for optimal health influenced the
excitability of the corticospinal tract projecting to the knee extensor muscles.
Irrespective of age and sex, individuals who achieved >10,000 steps/day had lower
corticospinal excitability than those who performed <10,000 steps/day, possibly
representing greater control of inhibitory and excitatory networks. Physical
activity involving >10,000 steps/day may mediate its effects on the nervous
system by decreasing corticospinal excitability.
PMID- 28495849
TI - Neoadjuvant Trials in ER+ Breast Cancer: A Tool for Acceleration of Drug
Development and Discovery.
AB - Neoadjuvant therapy trials offer an excellent strategy for drug development and
discovery in breast cancer, particularly in triple-negative and HER2
overexpressing subtypes, where pathologic complete response is a good surrogate
of long-term patient benefit. For estrogen receptor-positive (ER+) breast
cancers, however, use of this strategy has been challenging because of the lack
of validated surrogates of long-term efficacy and the overall good prognosis of
the majority of patients with this cancer subtype. We review below the clinical
benefits of neoadjuvant endocrine therapy for ER+/HER2-negative breast cancer,
its use and limitations for drug development, prioritization of adjuvant and
metastatic trials, and biomarker discovery.Significance: Neoadjuvant endocrine
therapy is an excellent platform for the development of investigational drugs,
triaging of novel combinations, biomarker validation, and discovery of mechanisms
of drug resistance. This review summarizes the clinical and investigational
benefits of this approach, with a focus on how to best integrate predictive
biomarkers into novel clinical trial designs. Cancer Discov; 7(6); 561-74.
(c)2017 AACR.
PMID- 28495851
TI - Different macrophages equally induce EMT in endometria of adenomyosis and normal.
AB - Endometrial cells and microenvironment are two important factors in the
pathogenesis of adenomyosis. Our previous study demonstrated that macrophages can
induce eutopic epithelial cells of adenomyosis to suffer from epithelial
mesenchymal transition (EMT). The aim of this study is to detect whether
macrophages interacting with epithelial cells equally induce the EMT process in
normal and eutopic endometria of healthy and adenomyotic patients; and whether
macrophages parallelly polarize to M2. We investigated the expression levels of
epithelial cadherin (E-cadherin), neural cadherin (N-cadherin), cytokeratin7
(CK7), vimentin, transforming growth factor-beta1 (TGFB1), SMAD3 and pSMAD3 using
immunohistochemistry and western blot, and then estimated the genetic levels of
CD163, IL10 and MMP12 using real-time quantitative polymerase chain reaction (RT
PCR) in macrophages. Eutopic and normal endometrial tissues were obtained from 20
patients with adenomyosis and 11 control patients without adenomyosis,
respectively. The immunohistochemical analysis shows distinct EMT in eutopic
endometria in secretory phase; the expression levels of TGFB1, SMAD3 and pSMAD3
that indicate signal pathway of EMT were also higher in secretory phase.
Macrophages can induce EMT process in primary endometrial epithelial cells
derived from normal and eutopic endometria. After co-culturing, THP-1-derived
macrophages polarized to M2. Compared with the eutopic endometrium group, further
polarization to M2 was observed in the normal endometrium group. These results
indicate that adenomyosis may be promoted by the pathologic EMT of epithelial
cells, which is induced by macrophages that incapably polarize to M2.
PMID- 28495852
TI - High-throughput mRNA sequencing of stromal cells from endometriomas and
endometrium.
AB - The aetiology of endometriosis is still unclear and to find mechanisms behind the
disease development, it is important to study each cell type from endometrium and
ectopic lesions independently. The objective of this study was to uncover
complete mRNA profiles in uncultured stromal cells from paired samples of
endometriomas and eutopic endometrium. High-throughput mRNA sequencing revealed
over 1300 dysregulated genes in stromal cells from ectopic lesions, including
several novel genes in the context of endometriosis. Functional annotation
analysis of differentially expressed genes highlighted pathways related to cell
adhesion, extracellular matrix-receptor interaction and complement and
coagulation cascade. Most importantly, we found a simultaneous upregulation of
complement system components and inhibitors, indicating major imbalances in
complement regulation in ectopic stromal cells. We also performed in vitro
experiments to evaluate the effect of endometriosis patients' peritoneal fluid
(PF) on complement system gene expression levels, but no significant impact of PF
on C3, CD55 and CFH levels was observed. In conclusion, the use of isolated
stromal cells enables to determine gene expression levels without the background
interference of other cell types. In the future, a new standard design studying
all cell types from endometriotic lesions separately should be applied to reveal
novel mechanisms behind endometriosis pathogenesis.
PMID- 28495853
TI - Transgenerational transmission of asthma risk after exposure to environmental
particles during pregnancy.
AB - Exposure to environmental particles during pregnancy increases asthma
susceptibility of the offspring. We tested the hypothesis that this transmission
continues to F2 and F3 generations and occurs via epigenetic mechanisms. We
compared allergic susceptibility of three generations of BALB/c offspring after a
single maternal exposure during pregnancy to diesel exhaust particles or
concentrated urban air particles. After pregnant dams received intranasal
instillations of particle suspensions or control, their F1, F2, and F3 offspring
were tested in a low-dose ovalbumin protocol for sensitivity to allergic asthma.
We found that the elevated susceptibility after maternal exposure to particles
during pregnancy persists into F2 and, with lesser magnitude, into F3
generations. This was evident from elevated eosinophil counts in bronchoalveolar
lavage (BAL) fluid, histopathological changes of allergic airway disease, and
increased BAL levels of IL-5 and IL-13. We have previously shown that dendritic
cells (DCs) can mediate transmission of risk upon adoptive transfer. Therefore,
we used an enhanced reduced representation bisulfite sequencing protocol to
quantify DNA methylation in DCs from each generation. Distinct methylation
changes were identified in F1, F2, and F3 DCs. The subset of altered loci shared
across the three generations were not linked to known allergy genes or pathways
but included a number of genes linked to chromatin modification, suggesting
potential interaction with other epigenetic mechanisms (e.g., histone
modifications). The data indicate that pregnancy airway exposure to diesel
exhaust particles (DEP) triggers a transgenerationally transmitted asthma
susceptibility and suggests a mechanistic role for epigenetic alterations in DCs
in this process.
PMID- 28495855
TI - Marijuana smoke induces severe pulmonary hyperresponsiveness, inflammation, and
emphysema in a predictive mouse model not via CB1 receptor activation.
AB - Sporadic clinical reports suggested that marijuana smoking induces spontaneous
pneumothorax, but no animal models were available to validate these observations
and to study the underlying mechanisms. Therefore, we performed a systematic
study in CD1 mice as a predictive animal model and assessed the
pathophysiological alterations in response to 4-mo-long whole body marijuana
smoke with integrative methodologies in comparison with tobacco smoke. Bronchial
responsiveness was measured with unrestrained whole body plethysmography, cell
profile in the bronchoalveolar lavage fluid with flow cytometry, myeloperoxidase
activity with spectrophotometry, inflammatory cytokines with ELISA, and
histopathological alterations with light microscopy. Daily marijuana inhalation
evoked severe bronchial hyperreactivity after a week. Characteristic
perivascular/peribronchial edema, atelectasis, apical emphysema, and neutrophil
and macrophage infiltration developed after 1 mo of marijuana smoking; lymphocyte
accumulation after 2 mo; macrophage-like giant cells, irregular or destroyed
bronchial mucosa, goblet cell hyperplasia after 3 mo; and severe atelectasis,
emphysema, obstructed or damaged bronchioles, and endothelial proliferation at 4
mo. Myeloperoxidase activity, inflammatory cell, and cytokine profile correlated
with these changes. Airway hyperresponsiveness and inflammation were not altered
in mice lacking the CB1 cannabinoid receptor. In comparison, tobacco smoke
induced hyperresponsiveness after 2 mo and significantly later caused
inflammatory cell infiltration/activation with only mild emphysema. We provide
the first systematic and comparative experimental evidence that marijuana causes
severe airway hyperresponsiveness, inflammation, tissue destruction, and
emphysema, which are not mediated by the CB1 receptor.
PMID- 28495854
TI - Role of apoptosis and autophagy in tuberculosis.
AB - Tuberculosis (TB) is one of the oldest known human diseases and is transmitted by
the bacteria Mycobacterium tuberculosis (Mtb). TB has a rich history with
evidence of TB infections dating back to 5,800 bc TB is unique in its ability to
remain latent in an individual for decades, with the possibility of later
reactivation, causing widespread systemic symptoms. Currently, it is estimated
that more than one-third of the world's population (~2 billion people) are
infected with Mtb. Prolonged periods of therapy and complexity of treatment
regimens, especially in active infection, have led to poor compliance in patients
being treated for TB. Therefore, it is vitally important to have a thorough
knowledge of the pathophysiology of Mtb to understand the disease progression, as
well as to develop novel diagnostic tests and treatments. Alveolar macrophages
represent both the primary host cell and the first line of defense against the
Mtb infection. Apoptosis and autophagy of macrophages play a vital role in the
pathogenesis and also in the host defense against Mtb. This review will outline
the role of these two cellular processes in defense against Mtb with particular
emphasis on innate immunity and explore developing therapies aimed at altering
host responses to the disease.
PMID- 28495856
TI - Flavored e-cigarette liquids and cinnamaldehyde impair respiratory innate immune
cell function.
AB - Innate immune cells of the respiratory tract are the first line of defense
against pathogenic and environmental insults. Failure of these cells to perform
their immune functions leaves the host susceptible to infection and may
contribute to impaired resolution of inflammation. While combustible tobacco
cigarettes have been shown to suppress respiratory immune cell function, the
effects of flavored electronic cigarette liquids (e-liquids) and individual
flavoring agents on respiratory immune cell responses are unknown. We
investigated the effects of seven flavored nicotine-free e-liquids on primary
human alveolar macrophages, neutrophils, and natural killer (NK) cells. Cells
were challenged with a range of e-liquid dilutions and assayed for their
functional responses to pathogenic stimuli. End points included phagocytic
capacity (neutrophils and macrophages), neutrophil extracellular trap formation,
proinflammatory cytokine production, and cell-mediated cytotoxic response (NK
cells). E-liquids were then analyzed via mass spectrometry to identify individual
flavoring components. Three cinnamaldehyde-containing e-liquids exhibited dose
dependent broadly immunosuppressive effects. Quantitative mass spectrometry was
used to determine concentrations of cinnamaldehyde in each of the three e
liquids, and cells were subsequently challenged with a range of cinnamaldehyde
concentrations. Cinnamaldehyde alone recapitulated the impaired function observed
with e-liquid exposures, and cinnamaldehyde-induced suppression of macrophage
phagocytosis was reversed by addition of the small-molecule reducing agent 1,4
dithiothreitol. We conclude that cinnamaldehyde has the potential to impair
respiratory immune cell function, illustrating an immediate need for further
toxicological evaluation of chemical flavoring agents to inform regulation
governing their use in e-liquid formulations.
PMID- 28495857
TI - TGF-beta1 induces Fstl1 via the Smad3-c-Jun pathway in lung fibroblasts.
AB - Transforming growth factor (TGF)-beta1 has long been regarded as a central
mediator of tissue fibrosis. Follistatin-like 1 (Fstl1) is a crucial profibrotic
glycoprotein that is upregulated in fibrotic lung tissues, and it promotes
fibrogenesis via facilitating TGF-beta signaling. Here we examined the signaling
pathway by which TGF-beta1 upregulates Fstl1 expression in mouse pulmonary
fibroblasts. TGF-beta1 regulated Fstl1 expression at both the transcriptional and
translational levels. Although TGF-beta1 rapidly activated the Smad, MAPK, and
Akt pathways in lung fibroblasts, only Smad2/3 inhibition eliminated TGF-beta1
induced Fstl1 expression. Analysis of the luciferase reporter activity identified
a functional c-Jun transcription site in the Fstl1 promoter. Our results
suggested a critical role for the Smad3-c-Jun pathway in the regulation of Fstl1
expression by TGF-beta1 during fibrogenesis.
PMID- 28495858
TI - Comparative functional analysis of ribonuclease 1 homologs: molecular insights
into evolving vertebrate physiology.
AB - Pancreatic-type ribonucleases (ptRNases) comprise a class of highly conserved
secretory endoribonucleases in vertebrates. The prototype of this enzyme family
is ribonuclease 1 (RNase 1). Understanding the physiological roles of RNase 1 is
becoming increasingly important, as engineered forms of the enzyme progress
through clinical trials as chemotherapeutic agents for cancer. Here, we present
an in-depth biochemical characterization of RNase 1 homologs from a broad range
of mammals (human, bat, squirrel, horse, cat, mouse, and cow) and nonmammalian
species (chicken, lizard, and frog). We discover that the human homolog of RNase
1 has a pH optimum for catalysis, ability to degrade double-stranded RNA, and
affinity for cell-surface glycans that are distinctly higher than those of its
homologs. These attributes have relevance for human health. Moreover, the
functional diversification of the 10 RNase 1 homologs illuminates the regulation
of extracellular RNA and other aspects of vertebrate evolution.
PMID- 28495859
TI - alpha-Synuclein may cross-bridge v-SNARE and acidic phospholipids to facilitate
SNARE-dependent vesicle docking.
AB - Misfolded alpha-synuclein (A-syn) is widely recognized as the primal cause of
neurodegenerative diseases including Parkinson's disease and dementia with Lewy
bodies. The normal cellular function of A-syn has, however, been elusive. There
is evidence that A-syn plays multiple roles in the exocytotic pathway in the
neuron, but the underlying molecular mechanisms are unclear. A-syn has been known
to interact with negatively charged phospholipids and with vesicle SNARE protein
VAMP2. Using single-vesicle docking/fusion assays, we find that A-syn promotes
SNARE-dependent vesicles docking significantly at 2.5 uM. When phosphatidylserine
(PS) is removed from t-SNARE-bearing vesicles, the docking enhancement by A-syn
disappears and A-syn instead acts as an inhibitor for docking. In contrast,
subtraction of PS from the v-SNARE-carrying vesicles enhances vesicle docking
even further. Moreover, when we truncate the C-terminal 45 residues of A-syn that
participates in interacting with VAMP2, the promotion of vesicle docking is
abrogated. Thus, the results suggest that the A-syn's interaction with v-SNARE
through its C-terminal tail and its concurrent interaction with PS in trans
through its amphipathic N-terminal domain facilitate SNARE complex formation,
whereby A-syn aids SNARE-dependent vesicle docking.
PMID- 28495860
TI - P2X7 receptor cross-talk regulates ATP-induced pannexin 1 internalization.
AB - In the nervous system, extracellular ATP levels transiently increase in
physiological and pathophysiological circumstances, effecting key signalling
pathways in plasticity and inflammation through purinergic receptors. Pannexin 1
(Panx1) forms ion- and metabolite-permeable channels that mediate ATP release and
are particularly enriched in the nervous system. Our recent study demonstrated
that elevation of extracellular ATP triggers Panx1 internalization in a
concentration- and time-dependent manner. Notably, this effect was sensitive to
inhibition of ionotropic P2X7 purinergic receptors (P2X7Rs). Here, we report our
novel findings from the detailed investigation of the mechanism underlying P2X7R
Panx1 cross-talk in ATP-stimulated internalization. We demonstrate that
extracellular ATP triggers and is required for the clustering of P2X7Rs and Panx1
on Neuro2a cells through an extracellular physical interaction with the Panx1
first extracellular loop (EL1). Importantly, disruption of P2X7R-Panx1 clustering
by mutation of tryptophan 74 within the Panx1 EL1 inhibits Panx1 internalization.
Notably, P2X7R-Panx1 clustering and internalization are independent of P2X7R
associated intracellular signalling pathways (Ca2+ influx and Src activation).
Further analysis revealed that cholesterol is required for ATP-stimulated P2X7R
Panx1 clustering at the cell periphery. Taken together, our data suggest that
extracellular ATP induces and is required for Panx1 EL1-mediated, cholesterol
dependent P2X7R-Panx1 clustering and endocytosis. These findings have important
implications for understanding the role of Panx1 in the nervous system and
provide important new insights into Panx1-P2X7R cross-talk.
PMID- 28495861
TI - Testosterone treatment and cardiovascular and venous thromboembolism risk: what
is 'new'?
AB - In men, testosterone (T) production declines as a function of ageing. Late-onset
hypogonadism (LOH) is the most commonly used term to indicate this age-related
condition. In LOH, the relative clinical significance and the potential benefit
of testosterone treatment (TTh) are still the subject of strong criticisms in the
scientific community. The debate is further complicated by the recent position
statement of the US Food and Drug Administration (FDA) emphasizing that, in LOH,
the benefits and safety of TTh have not been fully established. Hence, the FDA
required a labeling change to inform patients about a possible increased
cardiovascular (CV) risk of TTh. Similar considerations were previously released
by the FDA and by Health Canada concerning a TTh-related venous thromboembolism
(VTE) risk. In this review, we will summarize the available evidence concerning a
possible link among TTh and CV and VTE risks. For this purpose, data derived from
epidemiological studies analyzing relationships between the aforementioned risks
and endogenous T levels will be analyzed. In addition, evidence deriving from
interventional studies including pharmacoepidemiological and placebo-controlled
randomized controlled trials (RCTs) will be examined. Our analysis shows that
available data do not support an increased CV risk related to TTh. Similar
considerations can be drawn for the relationship between TTh and VTE. The
previously reported cases of TTh-related VTE were frequently related to a
previously undiagnosed thrombophilia-hypofibrinolysis status. Hence, an
anamnestic screening for thrombophilia before starting TTh is recommended, just
as it is for the use of oral contraceptives.
PMID- 28495862
TI - The Diagnosis-Wide Landscape of Hospital-Acquired AKI.
AB - BACKGROUND AND OBJECTIVES: The exploration of electronic hospital records offers
a unique opportunity to describe in-depth the prevalence of conditions associated
with diagnoses at an unprecedented level of comprehensiveness. We used a
diagnosis-wide approach, adapted from phenome-wide association studies (PheWAS),
to perform an exhaustive analysis of all diagnoses associated with hospital
acquired AKI (HA-AKI) in a French urban tertiary academic hospital over a period
of 10 years. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We retrospectively
extracted all diagnoses from an i2b2 (Informatics for Integrating Biology and the
Bedside) clinical data warehouse for patients who stayed in this hospital between
2006 and 2015 and had at least two plasma creatinine measurements performed
during the first week of their stay. We then analyzed the association between HA
AKI and each International Classification of Diseases (ICD)-10 diagnostic
category to draw a comprehensive picture of diagnoses associated with AKI.
Hospital stays for 126,736 unique individuals were extracted. RESULTS:
Hemodynamic impairment and surgical procedures are the main factors associated
with HA-AKI and five clusters of diagnoses were identified: sepsis, heart
diseases, polytrauma, liver disease, and cardiovascular surgery. The ICD-10 code
corresponding to AKI (N17) was recorded in 30% of the cases with HA-AKI
identified, and in this situation, 20% of the diagnoses associated with HA-AKI
corresponded to kidney diseases such as tubulointerstitial nephritis, necrotizing
vasculitis, or myeloma cast nephropathy. Codes associated with HA-AKI that
demonstrated the greatest increase in prevalence with time were related to
influenza, polytrauma, and surgery of neoplasms of the genitourinary system.
CONCLUSIONS: Our approach, derived from PheWAS, is a valuable way to
comprehensively identify and classify all of the diagnoses and clusters of
diagnoses associated with HA-AKI. Our analysis delivers insights into how
diagnoses associated with HA-AKI evolved over time. On the basis of ICD-10 codes,
HA-AKI appears largely underestimated in this academic hospital.
PMID- 28495865
TI - Ceramide counteracts the effects of ghrelin on the metabolic control of food
intake in rainbow trout.
AB - In mammals, ceramides are involved in the modulation of the orexigenic effects of
ghrelin (GHRL). We previously demonstrated in rainbow trout that
intracerebroventricular (ICV) treatment with ceramide (2.5 ug/100 g fish)
resulted in an anorexigenic response, i.e. a response opposed to that described
in mammals, where ceramide treatment is orexigenic. Therefore, we hypothesized
that the putative interaction between GHRL and ceramide must be different in
fish. Accordingly, in a first experiment, we observed that ceramide levels in the
hypothalamus of rainbow trout did not change after ICV treatment with GHRL. In a
second experiment, we assessed whether the effects of GHRL treatment on the
regulation of food intake in rainbow trout changed in the presence of ceramide.
Thus, we injected ICV GHRL and ceramide alone or in combination to evaluate in
hypothalamus and hindbrain changes in parameters related to the metabolic control
of food intake. The presence of ceramide generally counteracted the effects
elicited by GHRL on fatty acid-sensing systems, the capacity of integrative
sensors (AMPK, mTOR and SIRT-1), proteins involved in cellular signalling
pathways (Akt and FoxO1) and neuropeptides involved in the regulation of food
intake (AgRP, NPY, POMC and CART). The results are discussed in the context of
regulation of food intake by metabolic and endocrine inputs.
PMID- 28495863
TI - Soluble Urokinase Plasminogen Activator Receptor and Outcomes in Patients with
Diabetes on Hemodialysis.
AB - BACKGROUND AND OBJECTIVES: Soluble urokinase plasminogen activator receptor is a
novel biomarker strongly predictive of cardiovascular outcomes implicated in the
pathogenesis of kidney disease. Soluble urokinase plasminogen activator receptor
levels, however, correlate with declining kidney function. It is unclear whether
soluble urokinase plasminogen activator receptor levels remain associated with
outcomes in patients with ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We
measured plasma soluble urokinase plasminogen activator receptor levels in 1175
patients (mean age =66+/-8 years old, 54% men) with type 2 diabetes mellitus on
hemodialysis participating in the German Diabetes and Dialysis Study followed for
a median of 4 years for outcomes including all-cause death, cardiovascular
events, and infection-related mortality. Survival analysis was performed using
stepwise Cox proportional hazards models adjusted for potential confounders.
Also, adjustments were made for inflammatory markers (C-reactive protein and
leukocyte count) and the oxidative stress marker asymmetric dimethyl arginine to
investigate potential mediators of the relationship between soluble urokinase
plasminogen activator receptor and outcomes. RESULTS: Median soluble urokinase
plasminogen activator receptor levels were 10,521 pg/ml (interquartile range,
9105-12,543 pg/ml). When stratified by tertiles, patients with soluble urokinase
plasminogen activator receptor >11,633 pg/ml (third tertile) had adjusted 1.6
fold higher mortality (hazard ratio, 1.60; 95% confidence interval, 1.27 to 2.03)
compared with those with low soluble urokinase plasminogen activator receptor
<9599 pg/ml (first tertile). Risks of sudden death and stroke were higher
(adjusted hazard ratio, 1.98; 95% confidence interval, 1.27 to 3.09 and adjusted
hazard ratio, 1.74; 95% confidence interval, 1.05 to 2.90, respectively),
together accounting for higher incidence of cardiovascular events (adjusted
hazard ratio, 1.48; 95% confidence interval, 1.15 to 1.89). Associations with
outcomes persisted after adjusting for C-reactive protein, leukocyte count, and
asymmetric dimethyl arginine. Addition of soluble urokinase plasminogen activator
receptor to a risk factor model modestly improved risk discrimination for all
cause death (DeltaC statistic, 0.02; 95% confidence interval, 0.00 to 0.03) and
cardiovascular events (DeltaC statistic, 0.02; 95% confidence interval, 0.00 to
0.05). CONCLUSIONS: The association of soluble urokinase plasminogen activator
receptor levels with outcomes persists in patients on hemodialysis. Additional
study is warranted to characterize the underlying pathways of that association,
which may yield opportunities to develop new therapeutic strategies.
PMID- 28495866
TI - Sources of variance in immunological traits: evidence of congruent latitudinal
trends across species.
AB - Among-population differences in immunological traits allow assessment of both
evolutionary and plastic changes in organisms' resistance to pathogens. Such
knowledge also provides information necessary to predict responses of such traits
to environmental changes. Studies on latitudinal trends in insect immunity have
so far yielded contradictory results, suggesting that multispecies approaches
with highly standardised experimental conditions are needed. Here, we studied
among-population differences of two parameters reflecting constitutive immunity
phenoloxidase (PO) and lytic activity, using common-garden design on three
distantly related moth species represented by populations ranging from northern
Finland to Georgia (Caucasus). The larvae were reared at different temperatures
and on different host plants under a crossed factors experimental design.
Haemolymph samples for measurement of immune status were taken from the larvae
strictly synchronously. Clear among-population differences could be shown only
for PO activity in one species (elevated activity in the northern populations).
There was some indication that the cases of total absence of lytic activity were
more common in southern populations. The effects of temperature, host and sex on
the immunological traits studied remained highly species specific. Some evidence
was found that lytic activity may be involved in mediating trade-offs between
immunity and larval growth performance. In contrast, PO activity rarely covaried
with fitness-related traits, and neither were the values of PO and lytic activity
correlated with each other. The relatively inconsistent nature of the detected
patterns suggests that studies on geographic differences in immunological traits
should involve multiple species, and rely on several immunological indices if
general trends are a point of interest.
PMID- 28495867
TI - Sex differences in the utilization of essential and non-essential amino acids in
Lepidoptera.
AB - The different reproductive strategies of males and females underlie differences
in behavior that may also lead to differences in nutrient use between the two
sexes. We studied sex differences in the utilization of two essential amino acids
(EAAs) and one non-essential amino acid (NEAA) by the Carolina sphinx moth
(Manduca sexta). On day one post-eclosion from the pupae, adult male moths
oxidized greater amounts of larva-derived AAs than females, and more nectar
derived AAs after feeding. After 4 days of starvation, the opposite pattern was
observed: adult females oxidized more larva-derived AAs than males. Adult males
allocated comparatively small amounts of nectar-derived AAs to their first
spermatophore, but this allocation increased substantially in the second and
third spermatophores. Males allocated significantly more adult-derived AAs to
their flight muscle than females. These outcomes indicate that adult male and
female moths employ different strategies for allocation and oxidation of dietary
AAs.
PMID- 28495868
TI - Transforming growth factor beta-1 (TGF-beta1) stimulates collagen synthesis in
cultured rainbow trout cardiac fibroblasts.
AB - Cold acclimation of rainbow trout, Oncorhynchus mykiss, causes collagen to
increase within the extracellular matrix (ECM) of the myocardium, while warm
acclimation has the opposite effect. The mechanism responsible for this
remodelling response is not known. In mammals, transforming growth factor beta-1
(TGF-beta1) stimulates collagen deposition within the myocardial ECM. Therefore,
we hypothesized that TGF-beta1 regulates trout myocardial ECM turnover and
predicted that TGF-beta1 would induce collagen deposition in cultured rainbow
trout cardiac fibroblasts. We found that treatment of trout cardiac fibroblasts
with 15 ng ml-1 human recombinant TGF-beta1 caused an increase in total collagen
at 48 and 72 h and an increase in collagen type I protein after 7 days. We also
found that TGF-beta1 treatment caused an increase in the transcript abundance of
tissue inhibitor of metalloproteinase 2 (timp-2) and matrix metalloproteinase 9
(mmp-9) at 24 h. Cells treated with TGF-beta1 also had lower levels of the gene
transcript for mmp-2 after 48 h and higher levels of the gene transcript for
collagen type I alpha1 (col1a1) after 72 h. These changes in gene expression
suggest that the increase in collagen deposition is due to a decrease in the
activity of matrix metalloproteinases and an increase in collagen synthesis.
Together, these results indicate that TGF-beta1 is a regulator of ECM composition
in cultured trout cardiac fibroblasts and suggest that this cytokine may play a
role in regulating collagen content in the trout heart during thermal
acclimation.
PMID- 28495869
TI - Kinematics of ram filter feeding and beat-glide swimming in the northern anchovy
Engraulis mordax.
AB - In the dense aquatic environment, the most adept swimmers are streamlined to
reduce drag and increase the efficiency of locomotion. However, because they open
their mouth to wide gape angles to deploy their filtering apparatus, ram filter
feeders apparently switch between diametrically opposite swimming modes: highly
efficient, streamlined 'beat-glide' swimming, and ram filter feeding, which has
been hypothesized to be a high-cost feeding mode because of presumed increased
drag. Ram filter-feeding forage fish are thought to play an important role in the
flux of nutrients and energy in upwelling ecosystems; however, the biomechanics
and energetics of this feeding mechanism remain poorly understood. We quantified
the kinematics of an iconic forage fish, the northern anchovy, Engraulis mordax,
during ram filter feeding and non-feeding, mouth-closed beat-glide swimming.
Although many kinematic parameters between the two swimming modes were similar,
we found that swimming speeds and tailbeat frequencies were significantly lower
during ram feeding. Rather than maintain speed with the school, a speed which
closely matches theoretical optimum filter-feeding speeds was consistently
observed. Beat-glide swimming was characterized by high variability in all
kinematic parameters, but variance in kinematic parameters was much lower during
ram filter feeding. Under this mode, body kinematics are substantially modified,
and E. mordax swims more slowly and with decreased lateral movement along the
entire body, but most noticeably in the anterior. Our results suggest that
hydrodynamic effects that come with deployment of the filtering anatomy may limit
behavioral options during foraging and result in slower swimming speeds during
ram filtration.
PMID- 28495870
TI - Early life experience drives short-term acclimation of metabolic and
osmoregulatory traits in the leaf-eared mouse.
AB - We studied the putative effect of early life experience on the physiological
flexibility of metabolic and osmoregulatory traits in the leaf-eared mouse,
Phyllotis darwini, an altricial rodent inhabiting seasonal Mediterranean
environments. Adult individuals were collected in central Chile and maintained in
breeding pairs. Pups were isolated after weaning and acclimated to different
temperatures (cold or warm) and water availability (unrestricted and restricted)
until adulthood. Subsequently, individuals were re-acclimated to the opposite
treatment. Rodents reared in the warm and subjected to water restriction had
lower basal metabolic rate (BMR), total evaporative water loss (TEWL) and body
mass (Mb) compared with those developing in the cold treatment; nevertheless,
individuals subjected to warm temperatures had greater relative medullary
thickness (RMT) and urine concentrating ability (UCA). Cold-reared rodents re
acclimated to warm conditions exhibited physiological flexibility of metabolic
traits; however, their osmoregulatory attributes did not vary. Conversely, warm
reared rodents re-acclimated to cold had reduced RMT and UCA, but the metabolic
traits of these individuals did not change. These results suggest a trade-off
between metabolic performance and renal capabilities that might hinder
physiological acclimation. Our results support the hypothesis of ontogenetic
dependence of short-term acclimation in osmoregulatory and metabolic traits in P.
darwini.
PMID- 28495871
TI - Embryonic hypoxia programmes postprandial cardiovascular function in adult common
snapping turtles (Chelydra serpentina).
AB - Reduced oxygen availability (hypoxia) is a potent stressor during embryonic
development, altering the trajectory of trait maturation and organismal
phenotype. We previously documented that chronic embryonic hypoxia has a lasting
impact on the metabolic response to feeding in juvenile snapping turtles
(Chelydra serpentina). Turtles exposed to hypoxia as embryos [10% O2 (H10)]
exhibited an earlier and increased peak postprandial oxygen consumption rate,
compared with control turtles [21% O2 (N21)]. In the current study, we measured
central blood flow patterns to determine whether the elevated postprandial
metabolic response in H10 turtles is linked to lasting impacts on convective
transport. Five years after hatching, turtles were instrumented to quantify
systemic ([Formula: see text]) and pulmonary ([Formula: see text]) blood flows
and heart rate (fH) before and after a ~5% body mass meal. In adult N21 and H10
turtles, fH was increased significantly by feeding. Although total stroke volume
(VS,tot) remained at fasted values, this tachycardia contributed to an elevation
in total cardiac output ([Formula: see text]). However, there was a postprandial
reduction in a net left-right (L-R) shunt in N21 snapping turtles only. Relative
to N21 turtles, H10 animals exhibited higher [Formula: see text] due to increased
blood flow through the right systemic outflow vessels of the heart. This effect
of hypoxic embryonic development, reducing a net L-R cardiac shunt, may support
the increased postprandial metabolic rate we previously reported in H10 turtles,
and is further demonstration of adult reptile cardiovascular physiology being
programmed by embryonic hypoxia.
PMID- 28495872
TI - The planarian TRPA1 homolog mediates extraocular behavioral responses to near
ultraviolet light.
AB - Although light is most commonly thought of as a visual cue, many animals possess
mechanisms to detect light outside of the eye for various functions, including
predator avoidance, circadian rhythms, phototaxis and migration. Here we confirm
that planarians (like Caenorhabditis elegans, leeches and Drosophila larvae) are
capable of detecting and responding to light using extraocular photoreception. We
found that, when either eyeless or decapitated worms were exposed to near
ultraviolet (near-UV) light, intense wild-type photophobic behaviors were still
observed. Our data also revealed that behavioral responses to green wavelengths
were mediated by ocular mechanisms, whereas near-UV responses were driven by
extraocular mechanisms. As part of a candidate screen to uncover the genetic
basis of extraocular photoreception in the planarian species Schmidtea
mediterranea, we identified a potential role for a homolog of the transient
receptor potential channel A1 (TRPA1) in mediating behavioral responses to
extraocular light cues. RNA interference (RNAi) to Smed-TrpA resulted in worms
that lacked extraocular photophobic responses to near-UV light, a mechanism
previously only identified in Drosophila These data show that the planarian TRPA1
homolog is required for planarian extraocular-light avoidance and may represent a
potential ancestral function of this gene. TRPA1 is an evolutionarily conserved
detector of temperature and chemical irritants, including reactive oxygen species
that are byproducts of UV-light exposure. Our results suggest that planarians
possess extraocular photoreception and display an unconventional TRPA1-mediated
photophobic response to near-UV light.
PMID- 28495873
TI - Intestinal digestive enzyme modulation in house sparrow nestlings occurs within
24 h of a change in diet composition.
AB - Nestling house sparrows near fledging age (12 days) were previously found to
reversibly modulate the activity of their intestinal digestive enzymes in
response to changes in diet composition. However, it is not known how quickly
nestlings can adjust to new diets with different substrate compositions, nor is
it known how early in life nestlings can modulate their enzyme activity in
response to changes in diet. In the present study, 3-day-old nestlings were
captured from the wild and fed and switched among contrasting diets - one high in
protein and low in carbohydrate and another higher in carbohydrate and with
lower, but adequate, protein - in order to determine (1) how quickly house
sparrow nestlings could adjust to changes in diet composition, (2) how early in
life nestlings could modulate their digestive enzyme activity in response to
these changes and (3) which digestive enzymes could be modulated in house sparrow
nestlings earlier in life. We found that house sparrow nestlings as young as 3
days post-hatch were capable of modulating their intestinal disaccharidase
activity within 24 h of a change in diet composition, and nestlings gained the
ability to modulate aminopeptidase-N by 6 or 7 days of age. To our knowledge,
this is the first evidence of digestive enzyme modulation completed within 24 h
of a change in diet in an avian species and the first study to show intestinal
digestive enzyme modulation in response to changes in diet composition in any
animal this early in development.
PMID- 28495874
TI - Cranking up the heat: relationships between energetically costly song features
and the increase in thorax temperature in male crickets and katydids.
AB - Sexual displays of acoustically signalling insects are used in the context of
mate attraction and mate choice. While energetic investment in sound production
can increase the reproductive success of the sender, this entails metabolic
costs. Resource allocation to sexually selected, reproductive traits can trade
off against allocation to naturally selected traits (e.g. growth, immunity) when
individuals' energy budgets are limited. Estimating the magnitude of the costs
invested in acoustic signalling is necessary to understand this trade-off and its
influence on fitness and life history. To compare the costs associated with
acoustic signalling for two ensiferan species, we simultaneously took respiratory
measurements to record the rate of CO2 production and used infrared thermography
to measure the increase in thorax temperature. Furthermore, to identify what
combinations of acoustic parameters were energetically costly for the sender, we
recorded the calling songs of 22 different cricket and katydid species for a
comparative analysis and measured their thorax temperature while they sang.
Acoustic signalling was energetically costly for Mecopoda sp. and Anurogryllus
muticus, requiring a 12- and 16-fold increase over resting levels in the CO2
production rate. Moreover, calling increased thorax temperature, on average by
7.6 and 5.8 degrees C, respectively. We found that the song intensity and
effective calling rate, not simply the chirp/trill duty cycle or the pulse rate
alone, were good predictors for the thorax temperature increase in males.
PMID- 28495875
TI - Macrophage function in tissue repair and remodeling requires IL-4 or IL-13 with
apoptotic cells.
AB - Tissue repair is a subset of a broad repertoire of interleukin-4 (IL-4)- and IL
13-dependent host responses during helminth infection. Here we show that IL-4 or
IL-13 alone was not sufficient, but IL-4 or IL-13 together with apoptotic cells
induced the tissue repair program in macrophages. Genetic ablation of sensors of
apoptotic cells impaired the proliferation of tissue-resident macrophages and the
induction of anti-inflammatory and tissue repair genes in the lungs after
helminth infection or in the gut after induction of colitis. By contrast, the
recognition of apoptotic cells was dispensable for cytokine-dependent induction
of pattern recognition receptor, cell adhesion, or chemotaxis genes in
macrophages. Detection of apoptotic cells can therefore spatially
compartmentalize or prevent premature or ectopic activity of pleiotropic, soluble
cytokines such as IL-4 or IL-13.
PMID- 28495876
TI - A subcellular map of the human proteome.
AB - Resolving the spatial distribution of the human proteome at a subcellular level
can greatly increase our understanding of human biology and disease. Here we
present a comprehensive image-based map of subcellular protein distribution, the
Cell Atlas, built by integrating transcriptomics and antibody-based
immunofluorescence microscopy with validation by mass spectrometry. Mapping the
in situ localization of 12,003 human proteins at a single-cell level to 30
subcellular structures enabled the definition of the proteomes of 13 major
organelles. Exploration of the proteomes revealed single-cell variations in
abundance or spatial distribution and localization of about half of the proteins
to multiple compartments. This subcellular map can be used to refine existing
protein-protein interaction networks and provides an important resource to
deconvolute the highly complex architecture of the human cell.
PMID- 28495877
TI - A maternal-effect selfish genetic element in Caenorhabditis elegans.
AB - Selfish genetic elements spread in natural populations and have an important role
in genome evolution. We discovered a selfish element causing embryonic lethality
in crosses between wild strains of the nematode Caenorhabditis elegans The
element is made up of sup-35, a maternal-effect toxin that kills developing
embryos, and pha-1, its zygotically expressed antidote. pha-1 has long been
considered essential for pharynx development on the basis of its mutant
phenotype, but this phenotype arises from a loss of suppression of sup-35
toxicity. Inactive copies of the sup-35/pha-1 element show high sequence
divergence from active copies, and phylogenetic reconstruction suggests that they
represent ancestral stages in the evolution of the element. Our results suggest
that other essential genes identified by genetic screens may turn out to be
components of selfish elements.
PMID- 28495879
TI - Dual-comb spectroscopy of water vapor with a free-running semiconductor disk
laser.
AB - Dual-comb spectroscopy offers the potential for high accuracy combined with fast
data acquisition. Applications are often limited, however, by the complexity of
optical comb systems. Here we present dual-comb spectroscopy of water vapor using
a substantially simplified single-laser system. Very good spectroscopy
measurements with fast sampling rates are achieved with a free-running dual-comb
mode-locked semiconductor disk laser. The absolute stability of the optical comb
modes is characterized both for free-running operation and with simple microwave
stabilization. This approach drastically reduces the complexity for dual-comb
spectroscopy. Band-gap engineering to tune the center wavelength from the
ultraviolet to the mid-infrared could optimize frequency combs for specific gas
targets, further enabling dual-comb spectroscopy for a wider range of industrial
applications.
PMID- 28495880
TI - SOX4 Allows Facultative beta-Cell Proliferation Through Repression of Cdkn1a.
AB - The high-mobility group box transcription factor SOX4 is the most highly
expressed SOX family protein in pancreatic islets, and mutations in Sox4 are
associated with an increased risk of developing type 2 diabetes. We used an
inducible beta-cell knockout mouse model to test the hypothesis that Sox4 is
essential for the maintenance of beta-cell number during the development of type
2 diabetes. Knockout of Sox4 at 6 weeks of age resulted in time-dependent
worsening of glucose tolerance, impairment of insulin secretion, and diabetes by
30 weeks of age. Immunostaining revealed a decrease in beta-cell mass in knockout
mice that was caused by a 39% reduction in beta-cell proliferation. Gene
expression studies revealed that induction of the cell cycle inhibitor Cdkn1a was
responsible for the decreased proliferation in the knockout animals. Altogether,
this study demonstrates that SOX4 is necessary for adult beta-cell replication
through direct regulation of the beta-cell cycle.
PMID- 28495878
TI - Local amplifiers of IL-4Ralpha-mediated macrophage activation promote repair in
lung and liver.
AB - The type 2 immune response controls helminth infection and maintains tissue
homeostasis but can lead to allergy and fibrosis if not adequately regulated. We
have discovered local tissue-specific amplifiers of type 2-mediated macrophage
activation. In the lung, surfactant protein A (SP-A) enhanced interleukin-4 (IL
4)-dependent macrophage proliferation and activation, accelerating parasite
clearance and reducing pulmonary injury after infection with a lung-migrating
helminth. In the peritoneal cavity and liver, C1q enhancement of type 2
macrophage activation was required for liver repair after bacterial infection,
but resulted in fibrosis after peritoneal dialysis. IL-4 drives production of
these structurally related defense collagens, SP-A and C1q, and the expression of
their receptor, myosin 18A. These findings reveal the existence within different
tissues of an amplification system needed for local type 2 responses.
PMID- 28495881
TI - Dynamic expression and regulatory mechanism of TGF-beta signaling in chicken
embryonic stem cells differentiating into spermatogonial stem cells.
AB - The present study investigated the dynamic expression and regulatory mechanism of
transforming growth factor beta (TGF-beta) signaling involved in embryonic stem
cells (ESCs) differentiation into male germ cells. Candidate genes involved in
TGF-beta signaling pathway were screened from RNA-sequencing (RNA-seq), which
were further validated by quantitative real-time PCR (qRT-PCR). Bone
morphogenetic protein 4 (BMP4) was used to induce differentiation of ESCs in
vitro Inhibition of TGF-beta signaling pathway was reflected by Western blot of
SMAD2 and SMAD5 expression. Differentiating efficiency of germ cells was
evaluated by immunofluorescence and fluorescence-activated cell sorting (FACS).
Germ cell marker genes were assessed by qRT-PCR in the differentiation process,
with activation or inhibition of TGF-beta signaling pathway. In the process of in
vitro induction, SMAD2 and SMAD5 were found to significantly up-regulated in BMP4
group versus the control and inhibition groups after 4 and 14 days. Expression of
CKIT, CVH, DAZL, STRA8, and INTEGRIN alpha6 were significantly increased in the
BMP4 group compared with the control group, while down-regulated in the
inhibition groups. The proportion of germ cell-like cells was decreased from
17.9% to 2.2% after 4 days induction, and further decreased from 14.1% to 2.1%
after 14 days induction. Correspondingly, expression of marker genes in germ
cells was significantly lower. In vivo inhibition of TGF-beta signaling pathway
reduced germ cells formation from 5.5% to 1.6%, and down-regulated the expression
of CKIT, CVH, DAZL, STRA8, and INTEGRIN alpha6 In conclusion, our study reveals
the mechanism regulating spermatogonial stem cells (SSCs) and lays the basis for
further understanding of the regulatory network.
PMID- 28495883
TI - A systems biology analysis connects insulin receptor signaling with glucose
transporter translocation in rat adipocytes.
AB - Type 2 diabetes is characterized by insulin resistance, which arises from
malfunctions in the intracellular insulin signaling network. Knowledge of the
insulin signaling network is fragmented, and because of the complexity of this
network, little consensus has emerged for the structure and importance of the
different branches of the network. To help overcome this complexity, systems
biology mathematical models have been generated for predicting both the
activation of the insulin receptor (IR) and the redistribution of glucose
transporter 4 (GLUT4) to the plasma membrane. Although the insulin signal
transduction between IR and GLUT4 has been thoroughly studied with modeling and
time-resolved data in human cells, comparable analyses in cells from commonly
used model organisms such as rats and mice are lacking. Here, we combined
existing data and models for rat adipocytes with new data collected for the
signaling network between IR and GLUT4 to create a model also for their
interconnections. To describe all data (>140 data points), the model needed three
distinct pathways from IR to GLUT4: (i) via protein kinase B (PKB) and Akt
substrate of 160 kDa (AS160), (ii) via an AS160-independent pathway from PKB, and
(iii) via an additional pathway from IR, e.g. affecting the membrane
constitution. The developed combined model could describe data not used for
training the model and was used to generate predictions of the relative
contributions of the pathways from IR to translocation of GLUT4. The combined
model provides a systems-level understanding of insulin signaling in rat
adipocytes, which, when combined with corresponding models for human adipocytes,
may contribute to model-based drug development for diabetes.
PMID- 28495882
TI - Endoplasmic reticulum (ER) Ca2+-channel activity contributes to ER stress and
cone death in cyclic nucleotide-gated channel deficiency.
AB - Endoplasmic reticulum (ER) stress and mislocalization of improperly folded
proteins have been shown to contribute to photoreceptor death in models of
inherited retinal degenerative diseases. In particular, mice with cone cyclic
nucleotide-gated (CNG) channel deficiency, a model for achromatopsia, display
both early-onset ER stress and opsin mistrafficking. By 2 weeks of age, these
mice show elevated signaling from all three arms of the ER-stress pathway, and by
1 month, cone opsin is improperly distributed away from its normal outer segment
location to other retinal layers. This work investigated the role of Ca2+-release
channels in ER stress, protein mislocalization, and cone death in a mouse model
of CNG-channel deficiency. We examined whether preservation of luminal Ca2+
stores through pharmacological and genetic suppression of ER Ca2+ efflux protects
cones by attenuating ER stress. We demonstrated that the inhibition of ER Ca2+
efflux channels reduced all three arms of ER-stress signaling while improving
opsin trafficking to cone outer segments and decreasing cone death by 20-35%.
Cone-specific gene deletion of the inositol-1,4,5-trisphosphate receptor type I
(IP3R1) also significantly increased cone density in the CNG-channel-deficient
mice, suggesting that IP3R1 signaling contributes to Ca2+ homeostasis and cone
survival. Consistent with the important contribution of organellar Ca2+ signaling
in this achromatopsia mouse model, significant differences in dynamic
intraorganellar Ca2+ levels were detected in CNG-channel-deficient cones. These
results thus identify a novel molecular link between Ca2+ homeostasis and cone
degeneration, thereby revealing novel therapeutic targets to preserve cones in
inherited retinal degenerative diseases.
PMID- 28495884
TI - The uniqueness of subunit alpha of mycobacterial F-ATP synthases: An evolutionary
variant for niche adaptation.
AB - The F1F0 -ATP (F-ATP) synthase is essential for growth of Mycobacterium
tuberculosis, the causative agent of tuberculosis (TB). In addition to their
synthase function most F-ATP synthases possess an ATP-hydrolase activity, which
is coupled to proton-pumping activity. However, the mycobacterial enzyme lacks
this reverse activity, but the reason for this deficiency is unclear. Here, we
report that a Mycobacterium-specific, 36-amino acid long C-terminal domain in the
nucleotide-binding subunit alpha (Mtalpha) of F-ATP synthase suppresses its
ATPase activity and determined the mechanism of suppression. First, we employed
vesicles to show that in intact membrane-embedded mycobacterial F-ATP synthases
deletion of the C-terminal domain enabled ATPase and proton-pumping activity. We
then generated a heterologous F-ATP synthase model system, which demonstrated
that transfer of the mycobacterial C-terminal domain to a standard F-ATP synthase
alpha subunit suppresses ATPase activity. Single-molecule rotation assays
indicated that the introduction of this Mycobacterium-specific domain decreased
the angular velocity of the power-stroke after ATP binding. Solution X-ray
scattering data and NMR results revealed the solution shape of Mtalpha and the 3D
structure of the subunit alpha C-terminal peptide 521PDEHVEALDEDKLAKEAVKV540 of
M. tubercolosis (Mtalpha(521-540)), respectively. Together with cross-linking
studies, the solution structural data lead to a model, in which Mtalpha(521-540)
comes in close proximity with subunit gamma residues 104-109, whose interaction
may influence the rotation of the camshaft-like subunit gamma. Finally, we
propose that the unique segment Mtalpha(514-549), which is accessible at the C
terminus of mycobacterial subunit alpha, is a promising drug epitope.
PMID- 28495885
TI - Proteolytic cleavage of the hydrophobic domain in the CaValpha2delta1 subunit
improves assembly and activity of cardiac CaV1.2 channels.
AB - Voltage-gated L-type CaV1.2 channels in cardiomyocytes exist as heteromeric
complexes with the pore-forming CaValpha1, CaVbeta, and CaValpha2delta1 subunits.
The full complement of subunits is required to reconstitute the native-like
properties of L-type Ca2+ currents, but the molecular determinants responsible
for the formation of the heteromeric complex are still being studied. Enzymatic
treatment with phosphatidylinositol-specific phospholipase C, a phospholipase C
specific for the cleavage of glycosylphosphatidylinositol (GPI)-anchored
proteins, disrupted plasma membrane localization of the cardiac CaValpha2delta1
prompting us to investigate deletions of its hydrophobic transmembrane domain.
Patch-clamp experiments indicated that the C-terminally cleaved CaValpha2delta1
proteins up-regulate CaV1.2 channels. In contrast, deleting the residues before
the single hydrophobic segment (CaValpha2delta1 Delta1059-1063) impaired current
up-regulation. CaValpha2delta1 mutants G1060I and G1061I nearly eliminated the
cell-surface fluorescence of CaValpha2delta1, indicated by two-color flow
cytometry assays and confocal imaging, and prevented CaValpha2delta1-mediated
increase in peak current density and modulation of the voltage-dependent gating
of CaV1.2. These impacts were specific to substitutions with isoleucine residues
because functional modulation was partially preserved in CaValpha2delta1 G1060A
and G1061A proteins. Moreover, C-terminal fragments exhibited significantly
altered mobility in denatured immunoblots of CaValpha2delta1 G1060I and
CaValpha2delta1 G1061I, suggesting that these mutant proteins were impaired in
proteolytic processing. Finally, CaValpha2delta1 Delta1059-1063, but not
CaValpha2delta1 G1060A, failed to co-immunoprecipitate with CaV1.2. Altogether,
our data support a model in which small neutral hydrophobic residues facilitate
the post-translational cleavage of the CaValpha2delta1 subunit at the predicted
membrane interface and further suggest that preventing GPI anchoring of
CaValpha2delta1 averts its cell-surface expression, its interaction with
CaValpha1, and modulation of CaV1.2 currents.
PMID- 28495887
TI - A man with chest tightness and burning limbs.
PMID- 28495886
TI - The sigma-1 receptor modulates dopamine transporter conformation and cocaine
binding and may thereby potentiate cocaine self-administration in rats.
AB - The dopamine transporter (DAT) regulates dopamine (DA) neurotransmission by
recapturing DA into the presynaptic terminals and is a principal target of the
psychostimulant cocaine. The sigma-1 receptor (sigma1R) is a molecular chaperone,
and its ligands have been shown to modulate DA neuronal signaling, although their
effects on DAT activity are unclear. Here, we report that the prototypical
sigma1R agonist (+)-pentazocine potentiated the dose response of cocaine self
administration in rats, consistent with the effects of the sigmaR agonists PRE
084 and DTG (1,3-di-o-tolylguanidine) reported previously. These behavioral
effects appeared to be correlated with functional changes of DAT. Preincubation
with (+)-pentazocine or PRE-084 increased the Bmax values of [3H]WIN35428 binding
to DAT in rat striatal synaptosomes and transfected cells. A specific interaction
between sigma1R and DAT was detected by co-immunoprecipitation and
bioluminescence resonance energy transfer assays. Mutational analyses indicated
that the transmembrane domain of sigma1R likely mediated this interaction.
Furthermore, cysteine accessibility assays showed that sigma1R agonist
preincubation potentiated cocaine-induced changes in DAT conformation, which were
blocked by the specific sigma1R antagonist CM304. Moreover, sigma1R ligands had
distinct effects on sigma1R multimerization. CM304 increased the proportion of
multimeric sigma1Rs, whereas (+)-pentazocine increased monomeric sigma1Rs.
Together these results support the hypothesis that sigma1R agonists promote
dissociation of sigma1R multimers into monomers, which then interact with DAT to
stabilize an outward-facing DAT conformation and enhance cocaine binding. We
propose that this novel molecular mechanism underlies the behavioral potentiation
of cocaine self-administration by sigma1R agonists in animal models.
PMID- 28495890
TI - Paleoecology, Ploidy, Paleoatmospheric Composition, and Developmental Biology: A
Review of the Multiple Uses of Fossil Stomata.
PMID- 28495891
TI - Trimethylguanosine Synthase1 (TGS1) Is Essential for Chilling Tolerance.
AB - Chilling stress is a major factor limiting plant development and crop
productivity. Because the plant response to chilling is so complex, we are far
from understanding the genes important in the response to chilling. To identify
new genes important in chilling tolerance, we conducted a novel mutant screen,
combining a confirmed SALK T-DNA insertion collection with traditional forward
genetics. We screened a pool of more than 3700 confirmed homozygous SALK T-DNA
insertion lines for visible defects under prolonged growth at 5 degrees C. Of the
chilling-sensitive mutants we observed, mutations at one locus were characterized
in detail. This gene, At1g45231, encodes an Arabidopsis (Arabidopsis thaliana)
trimethylguanosine synthase (TGS1), previously uncharacterized in the plant
kingdom. We confirmed that Arabidopsis TGS1 is a functional ortholog of other
trimethylguanosine synthases based both on its in vitro methyltransferase
activity and on its ability to rescue the cold-growth inhibition of a
Saccharomyces cerevisiae tgs1Delta mutant in vivo. While tgs1 mutant plants grew
normally at 22 degrees C, their vegetative and reproductive growth was severely
compromised under chilling conditions. When we transgenically expressed TGS1 in
the mutant plants, the chilling-sensitive phenotype was relieved, demonstrating
that TGS1 is required for chilling tolerance.
PMID- 28495892
TI - Bacterial Biosensors for in Vivo Spatiotemporal Mapping of Root Secretion.
AB - Plants engineer the rhizosphere to their advantage by secreting various nutrients
and secondary metabolites. Coupling transcriptomic and metabolomic analyses of
the pea (Pisum sativum) rhizosphere, a suite of bioreporters has been developed
in Rhizobium leguminosarum bv viciae strain 3841, and these detect metabolites
secreted by roots in space and time. Fourteen bacterial lux fusion bioreporters,
specific for sugars, polyols, amino acids, organic acids, or flavonoids, have
been validated in vitro and in vivo. Using different bacterial mutants (nodC and
nifH), the process of colonization and symbiosis has been analyzed, revealing
compounds important in the different steps of the rhizobium-legume association.
Dicarboxylates and sucrose are the main carbon sources within the nodules; in
ineffective (nifH) nodules, particularly low levels of sucrose were observed,
suggesting that plant sanctions affect carbon supply to nodules. In contrast,
high myo-inositol levels were observed prior to nodule formation and also in nifH
senescent nodules. Amino acid biosensors showed different patterns: a gamma
aminobutyrate biosensor was active only inside nodules, whereas the phenylalanine
bioreporter showed a high signal also in the rhizosphere. The bioreporters were
further validated in vetch (Vicia hirsuta), producing similar results. In
addition, vetch exhibited a local increase of nod gene-inducing flavonoids at
sites where nodules developed subsequently. These bioreporters will be
particularly helpful in understanding the dynamics of root exudation and the role
of different molecules secreted into the rhizosphere.
PMID- 28495894
TI - Morbidity and Mortality Associated With Balloon Aortic Valvuloplasty: A National
Perspective.
AB - BACKGROUND: The introduction of transcatheter aortic valve replacement (TAVR) led
to renewed interest in balloon aortic valvuloplasty (BAV). We sought to assess
contemporary trends in BAV utilization and their outcomes. METHODS AND RESULTS:
The Nationwide Inpatient Sample was used to identify patients who underwent BAV
between 2004 and 2013. In-hospital morbidity and mortality, and predictors of
death after BAV were assessed. Outcomes of propensity-matched groups of patients
undergoing elective BAV or TAVR were evaluated. BAV utilization increased from
707 cases in 2004 to 3715 cases in 2013 (national estimates). Procedural and in
hospital mortality were 1.4% and 8.5%, respectively. Vascular complications
occurred in 7.0% of cases, blood transfusion in 17.5%, clinical stroke in 1.8%,
and pacemaker implantation in 3.0%. The strongest predictors of in-hospital death
were cardiogenic shock (odds ratio, 6.01; 95% confidence interval, 4.19-8.61;
P<0.001), need for left ventricular assist device (odds ratio, 3.48; 95%
confidence interval, 2.25-5.36; P<0.001), coagulopathy (odds ratio, 2.19; 95%
confidence interval, 1.51-3.18; P<0.001), and low institutional volume of BAV
(odds ratio, 1.58; 95% confidence interval, 1.06-2.37; P=0.03). In propensity
matched patients undergoing elective BAV or TAVR, rates of in-hospital mortality
(2.9% versus 3.5%; P=0.60), clinical stroke (1.6% versus 3.1%; P=0.10), and
vascular complications (8.2% versus 10.9%; P=0.14) were similar. However, BAV was
associated with lower rates of pacemaker implantation (2.9% versus 8.0%; P<0.001)
and blood transfusion (12.8% versus 22.9%; P<0.001). CONCLUSIONS: In a
contemporary national registry, BAV is associated with significant morbidity and
mortality that are similar to TAVR. With the substantial increase in BAV
utilization and the continuous improvement in TAVR outcomes, these data have
important implications to aid clinicians in the selection of appropriate BAV
candidates.
PMID- 28495893
TI - Rice Sucrose Partitioning Mediated by a Putative Pectin Methyltransferase and
Homogalacturonan Methylesterification.
AB - Homogalacturonan (HG) is the main component of pectins. HG methylesterification
has recently emerged as a key determinant controlling cell attachment, organ
formation, and phyllotaxy. However, whether and how HG methylesterification
affects intercellular metabolite transport has rarely been reported. Here, we
identified and characterized knockout mutants of the rice (Oryza sativa) OsQUA2
gene encoding a putative pectin methyltransferase. Osqua2 mutants exhibit a
remarkable decrease in the degree of methylesterification of HG in the culm-sieve
element cell wall and a markedly reduced grain yield. The culm of Osqua2 mutant
plants contains excessive sucrose (Suc), and a 13CO2 feeding experiment showed
that the Suc overaccumulation in the culm was caused by blocked Suc
translocation. These and other findings demonstrate that OsQUA2 is essential for
maintaining a high degree of methylesterification of HG in the rice culm-sieve
element cell wall, which may be critical for efficient Suc partitioning and grain
filling. In addition, our results suggest that the apoplastic pathway is involved
in long-distance Suc transport in rice. The identification and characterization
of the OsQUA2 gene and its functionality revealed a previously unknown
contribution of HG methylesterification and provided insight into how
modification of the cell wall regulates intercellular transport in plants.
PMID- 28495895
TI - Management of Patients With Cardiac Arrest Complicating Myocardial Infarction in
New York Before and After Public Reporting Policy Changes.
AB - BACKGROUND: In 2010, New York State began excluding selected patients with
cardiac arrest and coma from publicly reported mortality statistics after
percutaneous coronary intervention. We evaluated the effects of this exclusion on
rates of coronary angiography, revascularization, and mortality among patients
with acute myocardial infarction and cardiac arrest. METHODS AND RESULTS: Using
statewide hospitalization files, we identified discharges for acute myocardial
infarction and cardiac arrest January 2003 to December 2013 in New York and
several comparator states. A difference-in-differences approach was used to
evaluate the likelihood of coronary angiography, revascularization, and in
hospital mortality before and after 2010. A total of 26 379 patients with acute
myocardial infarction and cardiac arrest (5619 in New York) were included. Of
these, 17 141 (65%) underwent coronary angiography, 12 183 (46.2%) underwent
percutaneous coronary intervention, and 2832 (10.7%) underwent coronary artery
bypass grafting. Before 2010, patients with cardiac arrest in New York were less
likely to undergo percutaneous coronary intervention compared with referent
states (adjusted relative risk, 0.79; 95% confidence interval, 0.73-0.85;
P<0.001). This relationship was unchanged after the policy change (adjusted
relative risk, 0.82; 95% confidence interval, 0.76-0.89; interaction P=0.359).
Adjusted risks of in-hospital mortality between New York and comparator states
after 2010 were also similar (adjusted relative risk, 0.94; 95% confidence
interval, 0.87-1.02; P=0.152 for post- versus pre-2010 in New York; adjusted
relative risk, 0.88; 95% confidence interval, 0.84-0.92; P<0.001 for comparator
states; interaction P=0.103). CONCLUSIONS: Exclusion of selected cardiac arrest
cases from public reporting was not associated with changes in rates of
percutaneous coronary intervention or in-hospital mortality in New York. Rates of
revascularization in New York for cardiac arrest patients were lower throughout.
PMID- 28495896
TI - Percutaneous Coronary Intervention of Saphenous Vein Graft.
AB - BACKGROUND: Percutaneous coronary intervention (PCI) of saphenous vein grafts
(SVGs) has historically been associated with a high risk of adverse ischemic
events, but there is a paucity of contemporary data on the second-generation drug
eluting stent use within SVG, and the relative importance of high platelet
reactivity (HPR) in SVG PCI versus native lesion PCI is unknown. We studied
ischemic and bleeding events after SVG PCI and their association with HPR.
METHODS AND RESULTS: Subjects in the prospective, multicenter ADAPT-DES study
(Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) were
stratified according to whether they had PCI of an SVG or a non-SVG lesion. Two
year outcomes were compared between groups using univariate and multivariable Cox
proportional hazards models. HPR was defined as on-clopidogrel P2Y12 platelet
reaction units >208 as measured by the VerifyNow assay; major adverse cardiac
events were defined as the composite of cardiac death, myocardial infarction, or
stent thrombosis. Among 8582 subjects in ADAPT-DES, 405 (4.7%) had SVG PCI. SVG
PCI was independently associated with a higher 2-year risk of major adverse
cardiac events (adjusted hazard ratio, 2.34; 95% confidence interval, 1.69-3.23;
P<0.0001), ischemia-driven target vessel revascularization (adjusted hazard
ratio, 1.82; 95% confidence interval, 1.37-2.42; P<0.0001), and stent thrombosis
(adjusted hazard ratio, 2.26; 95% confidence interval, 1.42-3.59; P=0.0006), but
not of bleeding (adjusted hazard ratio, 0.99; 95% confidence interval, 0.68-1.46;
P=0.97). There was no statistical interaction between HPR and SVG PCI in regard
to major adverse cardiac events (adjusted Pinteraction=0.99). CONCLUSIONS: SVG
PCI is associated with a considerably higher risk of 2-year adverse ischemic
events, with HPR conferring similar risk in SVG and non-SVG PCI. More potent and
longer antiplatelet therapy may be beneficial for patients undergoing SVG PCI.
CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
identifier: NCT00638794.
PMID- 28495897
TI - Geographical Difference of the Interaction of Sex With Treatment Strategy in
Patients With Multivessel Disease and Left Main Disease: A Meta-Analysis From
SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery), PRECOMBAT (Bypass
Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left
Main Coronary Artery Disease), and BEST (Bypass Surgery and Everolimus-Eluting
Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery
Disease) Randomized Controlled Trials.
AB - BACKGROUND: The impact of sex on clinical outcomes of percutaneous coronary
intervention and coronary artery bypass graft for patients with multivessel
coronary disease and unprotected left main disease could be dissimilar between
Western and Asian populations. METHODS AND RESULTS: To assess clinical outcomes
after percutaneous coronary intervention or coronary artery bypass graft in women
and men with multivessel coronary disease and unprotected left main disease, a
pooled analysis (n=3280) was performed using the patient-level data from 3 large
randomized trials: SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery),
PRECOMBAT (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in
Patients With Left Main Coronary Artery Disease), and BEST (Bypass Surgery and
Everolimus-Eluting Stent Implantation in the Treatment of Patients with
Multivessel Coronary Artery Disease) trials. The primary end point was all-cause
death. Of 3280 patients, 794 patients (24.2%) were women. The median follow-up
period was 1806 days (1611-1837 days). In women, a high heterogeneity of the
treatment effect among the 3 trials was found for all-cause death (I2>50%),
whereas in men, it was consistent across the 3 trials. In the Western trial
(SYNTAX), female sex favored coronary artery bypass graft compared with
percutaneous coronary intervention (hazard ratio(percutaneous coronary
intervention) 2.213; 95% confidence interval, 1.242-3.943; P=0.007), whereas in
the Asian women (PRECOMBAT and BEST), the treatment effect was neutral between
both strategies. Sex interaction with treatment strategy was evident in the
Western trial (Pinteraction=0.019) but not in the Asian trials (PRECOMBAT
Pinteraction=0.469 and BEST Pinteraction=0.472; I2=58%). CONCLUSIONS: The present
meta-analysis suggested the presence of the heterogeneous sex-treatment
interaction across Asian and Western trials. Considering the ongoing
globalization of our medical practice, the heterogeneity of the sex-treatment
interaction needs to be well recognized and taken into account during the
decision making of the treatment strategy. CLINICAL TRIAL REGISTRATIONS: URL:
https://www.clinicaltrials.gov. Unique identifiers: NCT00114972, NCT00997828,
NCT00422968.
PMID- 28495898
TI - Balloon Aortic Valvuloplasty: Is It Still Relevant?
PMID- 28495899
TI - Public Reporting: Small Changes Lead to Minimal Impact.
PMID- 28495900
TI - Sex, Region, and Outcomes After Revascularization.
PMID- 28495901
TI - Red meat: another inconvenient truth.
PMID- 28495902
TI - Regio- and Stereo-Selective Oxidation of a Cardiovascular Drug, Metoprolol,
Mediated by Cytochrome P450 2D and 3A Enzymes in Marmoset Livers.
AB - A beta-blocker, metoprolol, is one of the in vivo probes for human cytochrome
P450 (P450) 2D6. Investigation of nonhuman primate P450 enzymes helps to improve
the accuracy of the extrapolation of pharmacokinetic data from animals into
humans. Common marmosets (Callithrix jacchus) are a potential primate model for
preclinical research, but the detailed roles of marmoset P450 enzymes in
metoprolol oxidation remain unknown. In this study, regio- and stereo-selectivity
of metoprolol oxidations by a variety of P450 enzymes in marmoset and human
livers were investigated in vitro. Although liver microsomes from cynomolgus
monkeys and rats preferentially mediated S-metoprolol O-demethylation and R
metoprolol alpha-hydroxylation, respectively, those from humans, marmosets,
minipigs, and dogs preferentially mediated R-metoprolol O-demethylation, in
contrast to the slow rates of R- and S-metoprolol oxidation in mouse liver
microsomes. R- and S-metoprolol O-demethylation activities in marmoset livers
were strongly inhibited by quinidine and ketoconazole, and were significantly
correlated with bufuralol 1'-hydroxylation and midazolam 1'-hydroxylation
activities and also with P450 2D and 3A4 contents, which is different from the
case in human livers that did not have any correlations with P450 3A-mediated
midazolam 1'-hydroxylation. Recombinant human P450 2D6 enzyme and marmoset P450
2D6/3A4 enzymes effectively catalyzed R-metoprolol O-demethylation, comparable to
the activities of human and marmoset liver microsomes, respectively. These
results indicated that the major roles of P450 2D enzymes for the regio- and
stereo-selectivity of metoprolol oxidation were similar between human and
marmoset livers, but the minor roles of P450 3A enzymes were unique to marmosets.
PMID- 28495903
TI - Health Care Service and Outcomes Among an Estimated 6.7 Million Ambulatory Care
Diabetic Foot Cases in the U.S.
AB - OBJECTIVE: To evaluate ambulatory clinical cases of diabetic foot ulcers (DFUs)
and diabetic foot infections (DFIs) in the U.S. from 2007 to 2013 and to assess
outcomes of emergency department or inpatient (ED/IP) admission, number of clinic
visits per year, and physician time spent per visit. RESEARCH DESIGN AND METHODS:
A cross-sectional historical cohort analysis was conducted by using the
nationally representative Centers for Disease Control and Prevention National
Ambulatory Medical Care Survey data from 2007 to 2013, including patients age
>=18 years with diabetes and either DFIs or DFUs. Study outcomes were analyzed by
using generalized linear models controlling for key demographics and chronic
conditions. RESULTS: Across the estimated 5.6 billion ambulatory care visits
between 2007 and 2013, 784.8 million involved diabetes and ~6.7 million (0.8%)
were for DFUs (0.3%) or DFIs (0.5%). Relative to other ambulatory clinical cases,
multivariable analyses indicated that DFUs were associated with a 3.4 times
higher odds of direct ED/IP admission (CI 1.01-11.28; P = 0.049), 2.1 times
higher odds of referral to another physician (CI 1.14-3.71; P = 0.017), 1.9 times
more visits in the past 12 months (CI 1.41-2.42; P < 0.001), and 1.4 times longer
time spent per visit with the physician (CI 1.03-1.87; P = 0.033). DFIs were
independently associated with a 6.7 times higher odds of direct ED referral or IP
admission (CI 2.25-19.51; P < 0.001) and 1.5 times more visits in the past 12
months (CI 1.14-1.90; P = 0.003). CONCLUSIONS: This investigation of an estimated
6.7 million diabetic foot cases indicates markedly greater risks for both ED/IP
admissions and number of outpatient visits, with DFUs also associated with a
higher odds of referrals to other physicians and longer physician visit times.
PMID- 28495905
TI - Long-term outcomes of the Boston type I keratoprosthesis in eyes with previous
herpes simplex virus keratitis.
AB - PURPOSE: To report the long-term outcomes of the Boston type I keratoprosthesis
(Kpro) in eyes with prior herpes simplex virus (HSV) keratitis. METHODS:
Retrospective review of all Kpro procedures performed by a single surgeon from 1
May 2004 to 1 January 2015. RESULTS: 13 of 173 Kpro procedures were performed in
11 eyes with prior HSV keratitis. There was not a significant difference in the
percentage of eyes with and without prior HSV keratitis with preoperative (9% vs
8%, p=1.00) or postoperative (57% vs 60%, p=1.00) corrected distance visual
acuity (CDVA) >=20/200 or in the percentage of contralateral eyes with
preoperative CDVA >=20/50 (55% vs 30%, p=0.18). While several postoperative
complications occurred approximately twice as often in eyes with prior HSV
keratitis, including persistent epithelial defect (63.6% vs 34.1%; p=0.10),
corneal infiltrate (27.3% vs 12.3%; p=0.17) and sterile vitritis (18.2% vs 9.4%;
p=0.31), only cystoid macular oedema (45.5% vs 12.3%; p=0.01) was significantly
more common. Similarly, while the Kpro retention failure rate in eyes with prior
HSV keratitis was twice than that in eyes without it (0.15 vs 0.07 per year), the
difference was not statistically significant (p=0.09). CONCLUSION: As greater
than half of patients with unilateral HSV keratitis undergoing Kpro implantation
have CDVA >=20/50 in the contralateral eye, and as the Kpro retention failure
rate in eyes with prior HSV keratitis is twice than that in eyes without prior
HSV keratitis, caution should be exercised when considering Kpro implantation in
these patients.
PMID- 28495904
TI - Assessing total retinal blood flow in diabetic retinopathy using multiplane en
face Doppler optical coherence tomography.
AB - AIM: To assess total retinal blood flow (TRBF) in diabetic retinopathy (DR) using
multiplane en face Doppler optical coherence tomography (OCT). METHODS: A 70 kHz
spectral-domain OCT system scanned a 2*2 mm area centred at the optic disc of the
eyes with DR and healthy participants. The multiplane en face Doppler OCT
algorithm generated a three-dimensional volumetric data set consisting of 195 en
face planes. The TRBF was calculated from the maximum flow values of each
branching retinal vein at an optimised en face plane. DR severity was graded
according to the international clinical classification system. The generalised
linear model method was used to compare flow values between DR groups and the
control group. RESULTS: A total of 71 eyes from 71 participants were included.
Ten eyes were excluded due to poor image quality. The within-visit repeatability
of scans was 4.1% (coefficient of variation). There was no significant difference
in the TRBF between the healthy (46.7+/-10.2 uL/min) and mild/moderate non
proliferative DR (44.9+/-12.6 uL/min) groups. The TRBF in severe non
proliferative DR (39.1+/-12.6 uL/min) and proliferative DR (28.9+/-8.85 uL/min)
groups were significantly lower (p=0.04 and p<0.0001, respectively) than that of
the healthy group. TRBF was correlated with DR disease severity (p<0.0001, linear
trend test). CONCLUSION: The novel multiplane en face Doppler OCT method provided
reliable measurements of TRBF in DR eyes. This may be a useful tool in
understanding the pathophysiology of DR.
PMID- 28495906
TI - Emergency corneal grafting in the UK: a 6-year analysis of the UK Transplant
Registry.
AB - BACKGROUND: Corneal graft (CG) surgery is the most common and successful tissue
transplant worldwide. A small and important group of patients are operated in
emergency situations, typically to save a perforated eye. Our knowledge of the
indications and outcomes of emergency corneal graft (eCG) is limited. METHODS:
Retrospective, multifactorial analysis of all CGs registered by the UK Transplant
Service from April 1999 to March 2005. RESULTS: A total of 12 976 CGs were
performed. 1330 (11.4%) were eCGs including 433 regrafts. Actual perforation
occurred in 876 (65.9%) patients. 420 (31.5%) grafts were for tectonic purposes
alone and 217 (16.3%) were also grafted for visual rehabilitation. The main
diagnostic categories were infection (39.4%), non-infectious ulcerative keratitis
(32.2%) and other causes (ectasias, previous ocular surgery, injury, dystrophies
and opacification). Graft survival of first eCG at 1, 2 and 5 years was 78%, 66%
and 47%, respectively. Best-corrected visual acuity of surviving grafts at 1 year
was: 6/12 or better in 29.9%, 6/18 to 6/60 in 38.4%, counting finger to LP in
30.6% and NPL in 1%, with worsening of vision in only 8.7% of the patients.
CONCLUSION: This study which is the largest of its kind shows that despite the
seriousness of the critical corneal pathology and the surgical challenges that it
poses, the outcomes of eCG are favourable with most patients keeping their
eyesight and avoiding immediate rejection. These clinical outcomes show the value
of eye banking facilities that are developed to support corneal tissue supply for
eCG.
PMID- 28495907
TI - Interdevice comparison of retinal sensitivity assessments in a healthy
population: the CenterVue MAIA and the Nidek MP-3 microperimeters.
AB - BACKGROUND: To compare and correlate the retinal sensitivity measurements
obtained with Nidek Microperimetry-3 (MP-3) and the CenterVue Macular Integrity
Assessment (MAIA) microperimeters among healthy subjects. METHODS: In this
prospective comparative study, 31 eyes of 23 subjects underwent complete
ophthalmological examination including retinal sensitivity assessments using two
microperimeters, the MP-3 (Nidek Technologies) and the MAIA (CenterVue). The mean
retinal sensitivity (dB) and its corresponding luminance (asb) and contrast (log
units) were analysed between the two instruments. The interdevice reproducibility
and level of agreement between the sensitivity values of the devices were
assessed. RESULTS: The mean retinal sensitivity (dB) measured by the MP-3
(25.02+/-1.06 dB, range: 20.90-26.70) was significantly (p<0.0001) lower compared
with the MAIA (30.68+/-0.74 dB, range: 28-31.84). The luminosity levels were
significantly (p<0.0001) higher with the MP3 (7.75+/-1.31 asb, range: 6.44-9.06)
compared with the MAIA (0.92+/-0.14 asb, range: 0.78-1.06). The contrast
sensitivity was significantly higher for the MP-3 (0.94+/-0.33 log units, range:
0.61-1.27) compared with the MAIA (0.23+/-0.03 log units, range: 0.20-0.26).
Despite these absolute differences, the intraclass coefficient was 0.85 (95% CI
0.70 to 0.92) between the two devices after applying a standard correction factor
to each data point (MAIA sensitivity=MP-3 sensitivity+5.65) with a mean
difference between MAIA and MP-3 of 0.01. CONCLUSION: Retinal sensitivity
measures higher, but luminance and contrast sensitivity measure lower for MAIA
generated values compared with the MP-3. The relationships, however, appeared
fairly consistent, and application of a standard correction factor allowed the
data to be inter-related, at least for normal eyes.
PMID- 28495908
TI - Towards cultural materialism in the medical humanities: the case of blood
rejuvenation.
AB - This paper argues for an approach within the medical humanities that draws on the
theoretical legacy of cultural materialism as a framework for reading cultural
practices and their relationship to the social and economic order. It revisits
the origins and development of cultural materialism in cultural studies and
literary studies between the 1970s and 1990s and considers how, with adaptation,
this methodology might facilitate ideological criticism focused on material
formations of health, disease and the human body. I outline three key
characteristics of a medicocultural materialist approach along these lines: (a)
interdisciplinary work on a broad range of medical and cultural sources,
including those drawn from 'popular' forms of culture; (b) the combination of
historicist analysis with scrutiny of present-day contexts; (c) analyses that
engage with political economy perspectives and/or the work of medical sociology
in this area. The subsequent sections of the paper employ a medicocultural
materialist approach to examine conjectural understandings of, and empirical
investigations into, the capacity of transfused human blood to rejuvenate the
ageing body. I trace textual faultlines that expose the structures of power which
inform the movement of blood between bodies in 'medical gothic' fictions from the
19th-century fin de siecle, including Mary Elizabeth Braddon's 'Good Lady
Ducayne' (1896) and Bram Stoker's Dracula (1897). I conclude with a critique of
biomedical innovations in blood rejuvenation in the era of medical neoliberalism,
before considering the potential applications of medicocultural materialism to
other topics within the field of the medical humanities.
PMID- 28495909
TI - Pulse wave velocity is associated with cognitive impairment in hemodialysis
patients.
AB - Cognitive impairment in hemodialysis patients is common and associated with
adverse outcomes. So far, the underlying pathogenesis remains unclear. Therefore,
we examined the potential relationship between cognitive impairment and three
different categories of risk factors with particular focus on arterial stiffness
measured by pulse wave velocity (PWV). A total of 201 chronic hemodialysis
patients underwent cognitive testing under standardized conditions using the
Montreal Cognitive Assessment (MoCA). Demographic data including cardiovascular
risk factors, dialysis-associated factors as well as factors related to chronic
kidney disease (CKD) were analyzed. To account for arterial stiffness, PWV was
measured by ambulatory blood pressure monitoried with an oscillometric device
that records brachial blood pressure along with pulse waves. In our cohort, 60.2%
of patients showed pathological MoCA test results indicating cognitive
impairment. PWV was significantly associated with cognitive impairment apart from
age, educational level, diabetes, and hypercholesterolemia. High prevalence of
cognitive impairment in hemodialysis patients was confirmed. For the first time,
an association between cognitive impairment and arterial stiffness was detected
in a larger cohort of hemodialysis patients. Concerning the underlying
pathogenesis of cognitive impairment, current results revealed a potential
involvement of arterial stiffness, which has to be further evaluated in future
studies.
PMID- 28495910
TI - Oxidative imbalance and kidney damage in spontaneously hypertensive rats:
activation of extrinsic apoptotic pathways.
AB - In both humans and animals, essential hypertension acts as a risk factor for
subclinical kidney damage and precedes renal dysfunction. Several lines of
evidence indicate that hypertension and oxidative stress are closely related. The
increase in vascular oxidative stress plays a key role in the pathophysiological
consequences of hypertension, including kidney disease. Our study examined this
issue in spontaneously hypertensive rat (SHR), a reliable model of essential
hypertension. We used SHR 20 weeks old when hypertension is stably developed,
vascular remodeling started, but kidney function is preserved. We examined
plasmatic pro-oxidant and antioxidant status showing a significant alteration in
oxidative balance in SHR. As index of oxidative damage, we evaluated lipid
peroxidation in kidney, liver, and skeletal muscle, detecting a significant rise
in lipid peroxidation levels in all SHR tissues, particularly relevant in kidney.
In addition, we analyzed the expression of cytoplasmic antioxidant enzymes,
superoxide dismutase 1 (SOD1) and glutatione S-tranferasi P1 (GSTP1). In SHR
liver, SOD1 expression slight increased while we have not detected any variation
in other tissues. Concerning GSTP1, SHR renal tissues did not display variations
in enzyme expression, while in the other tissues, we observed a significant
increase in both monomeric and pro-apoptotic dimeric form of the enzyme. By
analyzing apoptotic signal, we founded c-Jun N-terminal kinase (JNK) activation
in all SHR tissues, but only kidney presented extrinsic apoptotic pathway
activation. Our results suggest that, in hypertensive animals with preserved
renal function, despite the remarkable oxidative damage of renal tissues, only
the extrinsic apoptotic pathway is activated.
PMID- 28495911
TI - Intratumoral Injection of HSV1716, an Oncolytic Herpes Virus, Is Safe and Shows
Evidence of Immune Response and Viral Replication in Young Cancer Patients.
AB - Purpose: HSV1716 is an oncolytic herpes simplex virus-1 (HSV-1) studied in adults
via injection into the brain and superficial tumors. To determine the safety of
administering HSV1716 to pediatric patients with cancer, we conducted a phase I
trial of image-guided injection in young patients with relapsed or refractory
extracranial cancers.Experimental Design: We delivered a single dose of 105 to
107 infectious units of HSV1716 via computed tomography-guided intratumoral
injection and measured tumor responses by imaging. Patients were eligible for up
to three more doses if they achieved stable disease. We monitored HSV-1 serum
titers and shedding by PCR and culture.Results: We administered a single dose of
HSV1716 to eight patients and two doses to one patient. We did not observe any
dose-limiting toxicities. Adverse events attributed to virus included low-grade
fever, chills, and mild cytopenias. Six of eight HSV-1 seronegative patients at
baseline showed seroconversion on day 28. Six of nine patients had detectable HSV
1 genomes by PCR in peripheral blood appearing on day +4 consistent with de novo
virus replication. Two patients had transient focal increases in metabolic
activity on 18fluorine-deoxyglucose PET, consistent with inflammatory reactions.
In one case, the same geographic region that flared later appeared necrotic on
imaging. No patient had an objective response to HSV1716.Conclusions:
Intratumoral HSV1716 is safe and well-tolerated without shedding in children and
young adults with late-stage, aggressive cancer. Viremia consistent with virus
replication and transient inflammatory reactions hold promise for future HSV1716
studies. Clin Cancer Res; 23(14); 3566-74. (c)2017 AACR.
PMID- 28495912
TI - Uncertainty in medicine.
PMID- 28495913
TI - Longitudinal fluorescence in situ hybridization reveals cytogenetic evolution in
myeloma relapsing after autologous transplantation.
AB - To investigate cytogenetic evolution after upfront autologous stem cell
transplantation for newly diagnosed myeloma we retrospectively analyzed
fluorescence in situ hybridization results of 128 patients with paired bone
marrow samples from the time of primary diagnosis and at relapse. High-risk
cytogenetic abnormalities (deletion 17p and/or gain 1q21) occurred more
frequently after relapse (odds ratio: 6.33; 95% confidence interval: 1.86-33.42;
P<0.001). No significant changes were observed for defined IGH translocations
[t(4;14); t(11;14); t(14;16)] or hyperdiploid karyotypes between primary
diagnosis and relapse. IGH translocations with unknown partners occurred more
frequently at relapse. New deletion 17p and/or gain 1q21 were associated with
cytogenetic heterogeneity, since some de novo lesions with different copy numbers
were present only in subclones. No distinct baseline characteristics were
associated with the occurrence of new high-risk cytogenetic abnormalities after
progression. Patients who relapsed after novel agent-based induction therapy had
an increased risk of developing high-risk aberrations (odds ratio 10.82; 95%
confidence interval: 1.65-127.66; P=0.03) compared to those who were treated with
conventional chemotherapy. Survival analysis revealed dismal outcomes regardless
of whether high-risk aberrations were present at baseline (hazard ratio, 3.53;
95% confidence interval: 1.53-8.14; P=0.003) or developed at relapse only (hazard
ratio, 3.06; 95% confidence interval: 1.09-8.59; P=0.03). Our results demonstrate
cytogenetic evolution towards high-risk disease after autologous transplantation
and underline the importance of repeated genetic testing in relapsed myeloma
(EudraCT number of the HD4 trial: 2004-000944-26).
PMID- 28495914
TI - E14a2 BCR-ABL1 transcript is associated with a higher rate of treatment-free
remission in individuals with chronic myeloid leukemia after stopping tyrosine
kinase inhibitor therapy.
PMID- 28495915
TI - Extracellular glycine is necessary for optimal hemoglobinization of erythroid
cells.
AB - Vertebrate heme synthesis requires three substrates: succinyl-CoA, which
regenerates in the tricarboxylic acid cycle, iron and glycine. For each heme
molecule synthesized, one atom of iron and eight molecules of glycine are needed.
Inadequate delivery of iron to immature erythroid cells leads to a decreased
production of heme, but virtually nothing is known about the consequence of an
insufficient supply of extracellular glycine on the process of hemoglobinization.
To address this issue, we exploited mice in which the gene encoding glycine
transporter 1 (GlyT1) was disrupted. Primary erythroid cells isolated from fetal
livers of GlyT1 knockout (GlyT1-/-) and GlyT1-haplodeficient (GlyT1+/-) embryos
had decreased cellular uptake of [2-14C]glycine and heme synthesis as revealed by
a considerable decrease in [2-14C]glycine and 59Fe incorporation into heme. Since
GlyT1-/- mice die during the first postnatal day, we analyzed blood parameters of
newborn pups and found that GlyT1-/- animals develop hypochromic microcytic
anemia. Our finding that Glyt1-deficiency causes decreased heme synthesis in
erythroblasts is unexpected, since glycine is a non-essential amino acid. It also
suggests that GlyT1 represents a limiting step in heme and, consequently,
hemoglobin production.
PMID- 28495916
TI - Myelodysplasia and liver disease extend the spectrum of RTEL1 related
telomeropathies.
PMID- 28495917
TI - Combining flow cytometry and WT1 assessment improves the prognostic value of pre
transplant minimal residual disease in acute myeloid leukemia.
PMID- 28495920
TI - The British Cardiovascular Society Annual Conference, Manchester, 5-7 June 2017:
the Vice-President's message.
PMID- 28495919
TI - Alternative TSSs are co-regulated in single cells in the mouse brain.
AB - Alternative transcription start sites (TSSs) have been extensively studied genome
wide for many cell types and have been shown to be important during development
and to regulate transcript abundance between cell types. Likewise, single-cell
gene expression has been extensively studied for many cell types. However, how
single cells use TSSs has not yet been examined. In particular, it is unknown
whether alternative TSSs are independently expressed, or whether they are co
activated or even mutually exclusive in single cells. Here, we use a previously
published single-cell RNA-seq dataset, comprising thousands of cells, to study
alternative TSS usage. We find that alternative TSS usage is a regulated process,
and the correlation between two TSSs expressed in single cells of the same cell
type is surprisingly high. Our findings indicate that TSSs generally are
regulated by common factors rather than being independently regulated or
stochastically expressed.
PMID- 28495921
TI - Heartbeat: Managing cardiovascular disease as a family of diseases in the
community.
PMID- 28495918
TI - Bone marrow morphology is a strong discriminator between chronic eosinophilic
leukemia, not otherwise specified and reactive idiopathic hypereosinophilic
syndrome.
AB - Chronic eosinophilic leukemia, not otherwise specified can be difficult to
distinguish from idiopathic hypereosinophilic syndrome according to the current
World Health Organization guideline. To examine whether the morphological
features of bone marrow might aid in the differential diagnosis of these two
entities, we studied a total of 139 patients with a diagnosis of chronic
eosinophilic leukemia, not otherwise specified (n=17) or idiopathic
hypereosinophilic syndrome (n=122). As a group, abnormal bone marrow
morphological features, resembling myelodysplastic syndromes, myeloproliferative
neoplasm or myelodysplastic/myeloproliferative neoplasm, were identified in
40/139 (27%) patients: 16 (94%) of those with chronic eosinophilic leukemia and
24 (20%) of those with hypereosinophilic syndrome. Abnormal bone marrow
correlated with older age (P<0.001), constitutional symptoms (P<0.001), anemia
(P=0.041), abnormal platelet count (P=0.002), organomegaly (P=0.008), elevated
lactate dehydrogenase concentration (P=0.005), abnormal karyotype (P<0.001), as
well as the presence of myeloid neoplasm-related mutations (P<0.001). Patients
with abnormal bone marrow had shorter survival (48.1 months versus not reached,
P<0.001), a finding which was independent of other confounding factors (P<0.001).
The association between abnormal bone marrow and shorter survival was also
observed in hypereosinophilic syndrome patients alone. In summary, most patients
with chronic eosinophilic leukemia, not otherwise specified and a proportion of
those with idiopathic hypereosinophilic syndrome show abnormal bone marrow
features similar to the ones encountered in patients with myelodysplastic
syndromes, myelodysplastic/myeloproliferative neoplasm or BCR-ABL1-negative
myeloproliferative neoplasm. Among patients who are currently considered to have
idiopathic hypereosinophilic syndrome, abnormal bone marrow is a strong indicator
of clonal hematopoiesis. Similar to other myeloid neoplasms, bone marrow
morphology should be one of the major criteria to distinguish patients with
chronic eosinophilic leukemia, not otherwise specified or clonal
hypereosinophilic syndrome from those with truly reactive idiopathic
hypereosinophilic syndrome.
PMID- 28495922
TI - Rituximab immunotherapy: it's getting personal.
PMID- 28495923
TI - Neutrophils: positive or negative?
PMID- 28495924
TI - A mitochondrial drug to treat AML.
PMID- 28495925
TI - Indoxyl sulfate, a uremic trigger for platelets.
PMID- 28495926
TI - Mobilizing plasmacytoid dendritic cells.
PMID- 28495927
TI - An infant with Pearson syndrome: a rare cause of congenital sideroblastic anemia
and bone marrow failure.
PMID- 28495928
TI - Cyclin D1-negative blastoid mantle cell lymphoma exhibiting cleaved to bilobated
cytomorphology.
PMID- 28495931
TI - Neutrophil Extracellular Traps Drive Endothelial-to-Mesenchymal Transition.
AB - OBJECTIVE: An excessive release and impaired degradation of neutrophil
extracellular traps (NETs) leads to the continuous exposure of NETs to the
endothelium in a variety of hematologic and autoimmune disorders, including lupus
nephritis. This study aims to unravel the mechanisms through which NETs
jeopardize vascular integrity. APPROACH AND RESULTS: Microvascular and
macrovascular endothelial cells were exposed to NETs, and subsequent effects on
endothelial integrity and function were determined in vitro and in vivo. We found
that endothelial cells have a limited capacity to internalize NETs via the
receptor for advanced glycation endproducts. An overflow of the phagocytic
capacity of endothelial cells for NETs resulted in the persistent extracellular
presence of NETs, which rapidly altered endothelial cell-cell contacts and
induced vascular leakage and transendothelial albumin passage through elastase
mediated proteolysis of the intercellular junction protein VE-cadherin.
Furthermore, NET-associated elastase promoted the nuclear translocation of
junctional beta-catenin and induced endothelial-to-mesenchymal transition in
cultured endothelial cells. In vivo, NETs could be identified in kidney samples
of diseased MRL/lpr mice and patients with lupus nephritis, in whom the
glomerular presence of NETs correlated with the severity of proteinuria and with
glomerular endothelial-to-mesenchymal transition. CONCLUSIONS: These results
indicate that an excess of NETs exceeds the phagocytic capacity of endothelial
cells for NETs and promotes vascular leakage and endothelial-to-mesenchymal
transition through the degradation of VE-cadherin and the subsequent activation
of beta-catenin signaling. Our data designate NET-associated elastase as a
potential therapeutic target in the prevention of endothelial alterations in
diseases characterized by aberrant NET release.
PMID- 28495929
TI - Tissue Factor Prothrombotic Activity Is Regulated by Integrin-arf6 Trafficking.
AB - OBJECTIVE: Coagulation initiation by tissue factor (TF) is regulated by cellular
inhibitors, cell surface availability of procoagulant phosphatidylserine, and
thiol-disulfide exchange. How these mechanisms contribute to keeping TF in a
noncoagulant state and to generating prothrombotic TF remain incompletely
understood. APPROACH AND RESULTS: Here, we study the activation of TF in primary
macrophages by a combination of pharmacological, genetic, and biochemical
approaches. We demonstrate that primed macrophages effectively control TF cell
surface activity by receptor internalization. After cell injury, ATP signals
through the purinergic receptor P2rx7 induce release of TF+ microvesicles. TF
cell surface availability for release onto microvesicles is regulated by the
GTPase arf6 associated with integrin alpha4beta1. Furthermore, microvesicles
proteome analysis identifies activation of Galphai2 as a participating factor in
the release of microvesicles with prothrombotic activity in flowing blood. ATP
not only prevents TF and phosphatidylserine internalization but also induces TF
conversion to a conformation with high affinity for its ligand, coagulation
factor VII. Although inhibition of dynamin-dependent internalization also exposes
outer membrane procoagulant phosphatidylserine, the resulting TF+ microvesicles
distinctly lack protein disulfide isomerase and high affinity TF and fail to
produce fibrin strands typical for microvesicles generated by thrombo
inflammatory P2rx7 activation. CONCLUSIONS: These data show that procoagulant
phospholipid exposure is not sufficient and that TF affinity maturation is
required to generate prothrombotic microvesicles from a variety of cell types.
These findings are significant for understanding TF-initiated thrombosis and
should be considered in designing functional microvesicles-based diagnostic
approaches.
PMID- 28495930
TI - ADAMTS13 Retards Progression of Diabetic Nephropathy by Inhibiting Intrarenal
Thrombosis in Mice.
AB - OBJECTIVE: ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type I
repeats-13) prevents microvascular thrombosis by cleaving prothrombogenic
ultralarge von Willebrand factor (VWF) multimers. Clinical studies have found
association between reduced ADAMTS13-specific activity, ultralarge VWF multimers,
and thrombotic angiopathy in patients with diabetic nephropathy. It remains
unknown, however, whether ADAMTS13 deficiency or ultralarge VWF multimers have a
causative effect in diabetic nephropathy. APPROACH AND RESULTS: The extent of
renal injury was evaluated in wild-type (WT), Adamts13-/- and Adamts13-/-Vwf-/-
mice after 26 weeks of streptozotocin-induced diabetic nephropathy. We found that
WT diabetic mice exhibited low plasma ADAMTS13-specific activity and increased
VWF levels (P<0.05 versus WT nondiabetic mice). Adamts13-/- diabetic mice
exhibited deterioration of kidney function (increased albuminuria, plasma
creatinine, and urea; P<0.05 versus WT diabetic mice), independent of
hyperglycemia and hypertension. Deterioration of kidney function in Adamts13-/-
diabetic mice was concomitant with aggravated intrarenal thrombosis (assessed by
plasminogen activator inhibitor, VWF, fibrin(ogen), and CD41-positive
microthrombi), increased mesangial cell expansion, and extracellular matrix
deposition (P<0.05 versus WT diabetic mice). Genetic deletion of VWF in Adamts13
/- diabetic mice improved kidney function, inhibited intrarenal thrombosis, and
alleviated histological changes in glomeruli, suggesting that exacerbation of
diabetic nephropathy in the setting of ADAMTS13 deficiency is VWF dependent.
CONCLUSIONS: ADAMTS13 retards progression of diabetic nephropathy, most likely by
inhibiting VWF-dependent intrarenal thrombosis. Alteration in ADAMTS13-VWF
balance may be one of the key pathophysiological mechanisms of thrombotic
angiopathy in diabetes mellitus.
PMID- 28495932
TI - Effectiveness and Adoption of a Drawing-to-Learn Study Tool for Recall and
Problem Solving: Minute Sketches with Folded Lists.
AB - Drawing by learners can be an effective way to develop memory and generate visual
models for higher-order skills in biology, but students are often reluctant to
adopt drawing as a study method. We designed a nonclassroom intervention that
instructed introductory biology college students in a drawing method, minute
sketches in folded lists (MSFL), and allowed them to self-assess their recall and
problem solving, first in a simple recall task involving non-European alphabets
and later using unfamiliar biology content. In two preliminary ex situ
experiments, students had greater recall on the simple learning task, non
European alphabets with associated phonetic sounds, using MSFL in comparison with
a preferred method, visual review (VR). In the intervention, students studying
using MSFL and VR had ~50-80% greater recall of content studied with MSFL and, in
a subset of trials, better performance on problem-solving tasks on biology
content. Eight months after beginning the intervention, participants had shifted
self-reported use of drawing from 2% to 20% of study time. For a small subset of
participants, MSFL had become a preferred study method, and 70% of participants
reported continued use of MSFL. This brief, low-cost intervention resulted in
enduring changes in study behavior.
PMID- 28495933
TI - Curriculum Alignment with Vision and Change Improves Student Scientific Literacy.
AB - The Vision and Change in Undergraduate Biology Education final report challenged
institutions to reform their biology courses to focus on process skills and
student active learning, among other recommendations. A large southeastern
university implemented curricular changes to its majors' introductory biology
sequence in alignment with these recommendations. Discussion sections focused on
developing student process skills were added to both lectures and a lab, and one
semester of lab was removed. This curriculum was implemented using active
learning techniques paired with student collaboration. This study determined
whether these changes resulted in a higher gain of student scientific literacy by
conducting pre/posttesting of scientific literacy for two cohorts: students
experiencing the unreformed curriculum and students experiencing the reformed
curriculum. Retention of student scientific literacy for each cohort was also
assessed 4 months later. At the end of the academic year, scientific literacy
gains were significantly higher for students in the reformed curriculum (p =
0.005), with those students having double the scientific literacy gains of the
cohort in the unreformed curriculum. Retention of scientific literacy did not
differ between the cohorts.
PMID- 28495934
TI - How Should I Study for the Exam? Self-Regulated Learning Strategies and
Achievement in Introductory Biology.
AB - In college introductory science courses, students are challenged with mastering
large amounts of disciplinary content while developing as autonomous and
effective learners. Self-regulated learning (SRL) is the process of setting
learning goals, monitoring progress toward them, and applying appropriate study
strategies. SRL characterizes successful, "expert" learners, and develops with
time and practice. In a large, undergraduate introductory biology course, we
investigated: 1) what SRL strategies students reported using the most when
studying for exams, 2) which strategies were associated with higher achievement
and with grade improvement on exams, and 3) what study approaches students
proposed to use for future exams. Higher-achieving students, and students whose
exam grades improved in the first half of the semester, reported using specific
cognitive and metacognitive strategies significantly more frequently than their
lower-achieving peers. Lower-achieving students more frequently reported that
they did not implement their planned strategies or, if they did, still did not
improve their outcomes. These results suggest that many students entering
introductory biology have limited knowledge of SRL strategies and/or limited
ability to implement them, which can impact their achievement. Course-specific
interventions that promote SRL development should be considered as integral
pedagogical tools, aimed at fostering development of students' lifelong learning
skills.
PMID- 28495935
TI - Metacognition in Upper-Division Biology Students: Awareness Does Not Always Lead
to Control.
AB - Students with awareness and control of their own thinking can learn more and
perform better than students who are not metacognitive. Metacognitive regulation
is how you control your thinking in order to learn. It includes the skill of
evaluation, which is the ability to appraise your approaches to learning and then
modify future plans based on those appraisals. We asked when, why, and how upper
division biology students evaluated their approaches to learning. We used self
evaluation assignments to identify students with potentially high metacognition
and conducted semistructured interviews to collect rich qualitative data from
them. Through content analysis, we found that students evaluated their approaches
to learning when their courses presented novel challenges. Most students
evaluated in response to an unsatisfactory grade. While evaluating study
strategies, many students considered performance and learning simultaneously. We
gained insights on the barriers students face when they try to change their
approaches to learning based on their evaluations. A few students continued to
use ineffective study strategies even though they were aware of the
ineffectiveness of those strategies. A desire to avoid feeling uncomfortable was
the primary reason they avoided strategies that they knew were more effective. We
examined the behavioral change literature to help interpret these findings.
PMID- 28495936
TI - ASPECT: A Survey to Assess Student Perspective of Engagement in an Active
Learning Classroom.
AB - The primary measure used to determine relative effectiveness of in-class
activities has been student performance on pre/posttests. However, in today's
active-learning classrooms, learning is a social activity, requiring students to
interact and learn from their peers. To develop effective active-learning
exercises that engage students, it is important to gain a more holistic view of
the student experience in an active-learning classroom. We have taken a mixed
methods approach to iteratively develop and validate a 16-item survey to measure
multiple facets of the student experience during active-learning exercises. The
instrument, which we call Assessing Student Perspective of Engagement in Class
Tool (ASPECT), was administered to a large introductory biology class, and
student responses were subjected to exploratory factor analysis. The 16 items
loaded onto three factors that cumulatively explained 52% of the variation in
student response: 1) value of activity, 2) personal effort, and 3) instructor
contribution. ASPECT provides a rapid, easily administered means to measure
student perception of engagement in an active-learning classroom. Gaining a
better understanding of students' level of engagement will help inform instructor
best practices and provide an additional measure for comprehensively assessing
the impact of different active-learning strategies.
PMID- 28495937
TI - An Analysis of the Perceptions and Resources of Large University Classes.
AB - Large class learning is a reality that is not exclusive to the first-year
experience at midsized, comprehensive universities; upper-year courses have
similarly high enrollment, with many class sizes greater than 200 students.
Research into the efficacy and deficiencies of large undergraduate classes has
been ongoing for more than 100 years, with most research associating large
classes with weak student engagement, decreased depth of learning, and
ineffective interactions. This study used a multidimensional research approach to
survey student and instructor perceptions of large biology classes and to
characterize the courses offered by a department according to resources and
course structure using a categorical principal components analysis. Both student
and instructor survey results indicated that a large class begins around 240
students. Large classes were identified as impersonal and classified using
extrinsic qualifiers; however, students did identify techniques that made the
classes feel smaller. In addition to the qualitative survey, we also attempted to
quantify courses by collecting data from course outlines and analyzed the data
using categorical principal component analysis. The analysis maps institutional
change in resource allocation and teaching structure from 2010 through 2014 and
validates the use of categorical principal components analysis in educational
research. We examine what perceptions and factors are involved in a large class
that is perceived to feel small. Our analysis suggests that it is not the
addition of resources or difference in the lecturing method, but it is the
instructor that determines whether a large class can feel small.
PMID- 28495938
TI - Allergen immunotherapy for the treatment of allergic rhinitis and/or asthma: an
umbrella review.
AB - BACKGROUND: Allergic rhinitis and asthma are important public health concerns,
yet there is no consensus about the benefits and harms of allergen-specific
immunotherapy to treat these conditions. We performed an umbrella review of
systematic reviews summarizing the current evidence for the benefits and harms of
subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). METHODS:
We searched MEDLINE, Embase, the Cochrane Library and the grey literature from
Jan. 1, 2010 to Nov. 20, 2016 for systematic reviews of randomized controlled
trials or prospectively controlled studies involving children or adults with
allergic rhinitis or asthma. Outcomes were summarized narratively (benefits:
total combined symptom-medication score, symptom score, medication score, disease
specific quality of life, adherence; harms: anaphylaxis, death, local and
systemic reactions). RESULTS: Twenty-three systematic reviews were included. SCIT
and SLIT were more effective than placebo for most outcomes. SCIT was better than
SLIT at improving medication and symptom scores, with no differences in quality
of life; however, data were limited for this comparison. Anaphylaxis and death
were infrequently reported. Few reviews assessed benefits or harms among
children. INTERPRETATION: Allergen immunotherapy appears to be effective among
patients with allergic rhinitis and asthma. The safety of allergen immunotherapy
is not conclusively established, although death and anaphylaxis appear to be
rare. PROSPERO no.: CRD42015024590.
PMID- 28495939
TI - APOE*E4 Is Associated with Gray Matter Loss in the Posterior Cingulate Cortex in
Healthy Elderly Controls Subsequently Developing Subtle Cognitive Decline.
AB - BACKGROUND AND PURPOSE: The presence of apolipoprotein E4 (APOE*E4) is the
strongest currently known genetic risk factor for Alzheimer disease and is
associated with brain gray matter loss, notably in areas involved in Alzheimer
disease pathology. Our objective was to assess the effect of APOE*E4 on brain
structures in healthy elderly controls who subsequently developed subtle
cognitive decline. MATERIALS AND METHODS: This prospective study included 382
community-dwelling elderly controls. At baseline, participants underwent MR
imaging at 3T, extensive neuropsychological testing, and genotyping. After
neuropsychological follow-up at 18 months, participants were classified into
cognitively stable controls and cognitively deteriorating controls. Data analysis
included whole-brain voxel-based morphometry and ROI analysis of GM. RESULTS:
APOE*E4-related GM loss at baseline was found only in the cognitively
deteriorating controls in the posterior cingulate cortex. There was no APOE*E4
related effect in the hippocampus, mesial temporal lobe, or brain areas not
involved in Alzheimer disease pathology. Controls in the cognitively
deteriorating group had slightly lower GM concentration in the hippocampus at
baseline. Higher GM densities in the hippocampus, middle temporal lobe, and
amygdala were associated with a decreased risk for cognitively deteriorating
group status at follow-up. CONCLUSIONS: APOE*E4-related GM loss in the posterior
cingulate cortex (an area involved in Alzheimer disease pathology) was found only
in those elderly controls who subsequently developed subtle cognitive decline but
not in cognitively stable controls. This finding might explain the partially
conflicting results of previous studies that typically did not include detailed
neuropsychological assessment and follow-up. Most important, APOE*E4 status had
no impact on GM density in areas affected early by neurofibrillary tangle
formation such as the hippocampus and mesial temporal lobe.
PMID- 28495940
TI - Neuroimaging Changes in Menkes Disease, Part 2.
AB - This is the second part of a retrospective and review MR imaging study aiming to
define the frequency rate, timing, imaging features, and evolution of gray matter
changes in Menkes disease, a rare multisystem X-linked disorder of copper
metabolism characterized by early, severe, and progressive neurologic
involvement. According to our analysis, neurodegenerative changes and focal basal
ganglia lesions already appear in the early phases of the disease. Subdural
collections are less common than generally thought; however, their presence
remains important because they might challenge the differential diagnosis with
child abuse and might precipitate the clinical deterioration. Anecdotal findings
in our large sample seem to provide interesting clues about the protean
mechanisms of brain injury in this rare disease and further highlight the broad
spectrum of MR imaging findings that might be expected while imaging a child with
the suspicion of or a known diagnosis of Menkes disease.
PMID- 28495941
TI - Pontomesencephalic Atrophy and Postural Instability in Wilson Disease.
AB - BACKGROUND AND PURPOSE: The MR Parkinsonism index helps in differentiating
progressive supranuclear palsy from Parkinson disease and multisystem atrophy.
Pontomesencephalic involvement is common in neurologic Wilson disease, but there
is no prior study evaluating the MR Parkinsonism index and its indices in Wilson
disease. We report the MR Parkinsonism index and its indices in Wilson disease
and correlate these changes with clinical severity and postural reflex. MATERIALS
AND METHODS: Thirteen individuals with neurologic Wilson disease were included,
and their clinical details, including neurologic severity, postural reflex
abnormality, and location of signal changes on MR imaging, were noted. The 3D
BRAVO T1 sequence was used for measurement of the MR Parkinsonism index and its
indices. The MR Parkinsonism index and its indices were also obtained in 6 age-
and sex-matched controls. The morphometric parameters in Wilson disease were
compared with those in with healthy controls and among the patients with and
without abnormal postural reflex. RESULTS: The midbrain area was reduced in
patients with Wilson disease compared with controls (112.08 +/- 27.94 versus
171.95 +/- 23.66 mm2, P = .002). The patients with an abnormal postural reflex
had an increased MR Parkinsonism index and pons-to-midbrain ratio compared with
controls, whereas these parameters were equivalent in patients with normal
postural reflex and controls. The patients with abnormal postural reflex had more
severe illness, evidenced by higher Burke-Fahn-Marsden scores (51.0 +/- 32.27
versus 13.75 +/- 12.37, P = .04) and neurologic severity grades (2.57 +/- 0.53
versus 1.67 +/- 0.82, P = .04). CONCLUSIONS: An increase in the MR Parkinsonism
index in Wilson disease is mainly due to midbrain atrophy and it correlates with
neurologic severity and abnormal postural reflex.
PMID- 28495942
TI - TIPIC Syndrome: Beyond the Myth of Carotidynia, a New Distinct Unclassified
Entity.
AB - BACKGROUND AND PURPOSE: The differential diagnosis of acute cervical pain
includes nonvascular and vascular causes such as carotid dissection, carotid
occlusion, or vasculitis. However, some patients present with unclassified
vascular and perivascular changes on imaging previously reported as carotidynia.
The aim of our study was to improve the description of this as yet unclassified
clinico-radiologic entity. MATERIALS AND METHODS: From January 2009 through April
2016, 47 patients from 10 centers presenting with acute neck pain or tenderness
and at least 1 cervical image showing unclassified carotid abnormalities were
included. We conducted a systematic, retrospective study of their medical charts
and diagnostic and follow-up imaging. Two neuroradiologists independently
analyzed the blinded image datasets. RESULTS: The median patient age was 48
years. All patients presented with acute neck pain, and 8 presented with
transient neurologic symptoms. Imaging showed an eccentric pericarotidian
infiltration in all patients. An intimal soft plaque was noted in 16 patients,
and a mild luminal narrowing was noted in 16 patients. Interreader
reproducibility was excellent. All patients had complete pain resolution within a
median of 13 days. At 3-month follow-up, imaging showed complete disappearance of
vascular abnormalities in 8 patients, and a marked decrease in all others.
CONCLUSIONS: Our study improved the description of an unclassified, clinico
radiologic entity, which could be described by the proposed acronym: TransIent
Perivascular Inflammation of the Carotid artery (TIPIC) syndrome.
PMID- 28495943
TI - Retention of Gadolinium-Based Contrast Agents in Multiple Sclerosis:
Retrospective Analysis of an 18-Year Longitudinal Study.
AB - BACKGROUND AND PURPOSE: Gadolinium-based contrast agents have been associated
with lasting high T1-weighted signal intensity in the dentate nucleus and globus
pallidus, with histopathologically confirmed gadolinium retention. We aimed to
longitudinally investigate the relationship of multiple gadolinium-based contrast
agent administrations to the Signal Intensity Index in the dentate nucleus and
globus pallidus and any associations with cognitive function in multiple
sclerosis. MATERIALS AND METHODS: The Signal Intensity Index in the dentate
nucleus and globus pallidus was retrospectively evaluated on T1-weighted MR
imaging in an 18-year longitudinal cohort study of 23 patients with MS receiving
multiple gadolinium-based contrast agent administrations and 23 healthy age- and
sex-matched controls. Participants also underwent comprehensive
neuropsychological testing. RESULTS: Patients with MS had a higher Signal
Intensity Index in the dentate nucleus (P < .001), but not in the globus pallidus
(P = .19), compared with non-gadolinium-based contrast agent-exposed healthy
controls by an unpaired t test. Increasing numbers of gadolinium-based contrast
agent administrations were associated with an increased Signal Intensity Index in
the dentate nucleus (beta = 0.45, P < .001) and globus pallidus (beta = 0.60, P <
.001). This association remained stable with corrections for the age, disease
duration, and physical disability for both the dentate nucleus (beta = 0.43, P =
.001) and globus pallidus (beta = 0.58, P < .001). An increased Signal Intensity
Index in the dentate nucleus among patients with MS was associated with lower
verbal fluency scores, which remained significant after correction for several
aspects of disease severity (beta = -0.40 P = .013). CONCLUSIONS: Our data
corroborate previous reports of lasting gadolinium retention in brain tissues. An
increased Signal Intensity Index in the dentate nucleus and globus pallidus was
associated with lower verbal fluency, which does not prove causality but
encourages further studies on cognition and gadolinium-based contrast agent
administration.
PMID- 28495944
TI - What Does the Boxed Warning Tell Us? Safe Practice of Using Ferumoxytol as an MRI
Contrast Agent.
AB - BACKGROUND AND PURPOSE: Despite the label change and the FDA's boxed warning
added to the Feraheme (ferumoxytol) label in March 2015, radiologists have shown
increasing interest in using ferumoxytol as an MR imaging contrast agent as a
supplement or alternative to gadolinium. The goals of this study were to provide
information regarding ferumoxytol safety as an imaging agent in a single center
and to assess how the Feraheme label change may affect this potential, currently
off-label indication. MATERIALS AND METHODS: This retrospective study evaluated
the overall frequency of ferumoxytol-related adverse events when used for CNS MR
imaging. Patients with various CNS pathologies were enrolled in institutional
review board-approved imaging studies. Ferumoxytol was administered as multiple
rapid bolus injections. The risk of adverse events was correlated with
demographic data/medical history. RESULTS: The safety of 671 ferumoxytol-enhanced
MR studies in 331 patients was analyzed. No anaphylactic, life-threatening, or
fatal (grade 4 or 5) adverse events were recorded. The overall proportion of
ferumoxytol-related grade 1-3 adverse events was 10.6% (8.6% occurring within 48
hours), including hypertension (2.38%), nausea (1.64%), diarrhea (1.04%), and
headache (1.04%). History of 1 or 2 allergies was associated with an increased
risk of adverse events (14.61% versus 7.51% [no history]; P = .007). CONCLUSIONS:
The frequency of mild ferumoxytol-related adverse events was comparable with
literature results, and no serious adverse event was recorded. Although the
recommendations in the boxed warning should be followed, serious adverse events
appear to be rare, and with proper precautions, ferumoxytol may be a valuable MR
imaging agent.
PMID- 28495945
TI - Role of High-Resolution Dynamic Contrast-Enhanced MRI with Golden-Angle Radial
Sparse Parallel Reconstruction to Identify the Normal Pituitary Gland in Patients
with Macroadenomas.
AB - BACKGROUND AND PURPOSE: Preoperative localization of the pituitary gland with
imaging in patients with macroadenomas has been inadequately explored. The
pituitary gland enhancing more avidly than a macroadenoma has been described in
the literature. Taking advantage of this differential enhancement pattern, our
aim was to evaluate the role of high-resolution dynamic MR imaging with golden
angle radial sparse parallel reconstruction in localizing the pituitary gland in
patients undergoing trans-sphenoidal resection of a macroadenoma. MATERIALS AND
METHODS: A retrospective study was performed in 17 patients who underwent trans
sphenoidal surgery for pituitary macroadenoma. Radial volumetric interpolated
brain examination sequences with golden-angle radial sparse parallel technique
were obtained. Using an ROI-based method to obtain signal-time curves and
permeability measures, 3 separate readers identified the normal pituitary gland
distinct from the macroadenoma. The readers' localizations were then compared
with the intraoperative location of the gland. Statistical analyses were
performed to assess the interobserver agreement and correlation with operative
findings. RESULTS: The normal pituitary gland was found to have steeper
enhancement-time curves as well as higher peak enhancement values compared with
the macroadenoma (P < .001). Interobserver agreement was almost perfect in all 3
planes (kappa = 0.89). In the 14 cases in which the gland was clearly identified
intraoperatively, the correlation between the readers' localization and the true
location derived from surgery was also nearly perfect (kappa = 0.95).
CONCLUSIONS: This study confirms our ability to consistently and accurately
identify the normal pituitary gland in patients with macroadenomas with the
golden-angle radial sparse parallel technique with quantitative permeability
measurements and enhancement-time curves.
PMID- 28495946
TI - Neuroimaging Changes in Menkes Disease, Part 1.
AB - Menkes disease is a rare multisystem X-linked disorder of copper metabolism.
Despite an early, severe, and progressive neurologic involvement, our knowledge
of brain involvement remains unsatisfactory. The first part of this retrospective
and review MR imaging study aims to define the frequency rate, timing, imaging
features, and evolution of intracranial vascular and white matter changes.
According to our analysis, striking but also poorly evolutive vascular
abnormalities characterize the very early phases of disease. After the first
months, myelination delay becomes evident, often in association with protean
focal white matter lesions, some of which reveal an age-specific brain
vulnerability. In later phases of the disease, concomitant progressive
neurodegeneration might hinder the myelination progression. The currently
enriched knowledge of neuroradiologic finding evolution provides valuable clues
for early diagnosis, identifies possible MR imaging biomarkers of new treatment
efficacy, and improves our comprehension of possible mechanisms of brain injury
in Menkes disease.
PMID- 28495948
TI - Introduction of a Dedicated Emergency Department MR Imaging Scanner at the Barrow
Neurological Institute.
AB - Use of advanced imaging in the emergency department has been increasing in the
United States during the past 2 decades. This trend has been most notable in CT,
which has increased concern over the effects of increasing levels of medical
ionizing radiation. MR imaging offers a safe, nonionizing alternative to CT and
is diagnostically superior in many neurologic conditions encountered in the
emergency department. Herein, we describe the process of developing and
installing a dedicated MR imaging scanner in the Neuroscience Emergency
Department at the Barrow Neurological Institute and its effects on neuroradiology
and the emergency department in general.
PMID- 28495947
TI - Mechanical Thrombectomy with the Embolus Retriever with Interlinked Cages in
Acute Ischemic Stroke: ERIC, the New Boy in the Class.
AB - BACKGROUND AND PURPOSE: The Embolus Retriever with Interlinked Cages (ERIC)
device is a novel stent retriever for mechanical thrombectomy. It consists of
interlinked cages and could improve procedural benchmarks and clinical outcome
compared with classic stent retrievers. This study compares the rates of
recanalization, favorable clinical outcome, procedural adverse events, and
benchmarks between the ERIC device and classic stent retrievers. MATERIALS AND
METHODS: From 545 patients treated with thrombectomy between 2012 and 2015, 316
patients were included. The mean age was 69 +/-13 years, the mean baseline NIHSS
score was 17 +/- 5, and 174 (55%) were men. The ERIC was used as the primary
thrombectomy device in 59 (19%) patients. In a propensity score matched analysis
including the NIHSS score, clot location, delay to groin puncture,
neurointerventionalist, and anesthetic management, 57 matched pairs were
identified. RESULTS: Patients treated with the ERIC device compared with classic
stent retrievers showed equal rates of recanalization (86% versus 81%, P = .61),
equal favorable 3-month clinical outcome (mRS 0-2: 46% versus 40%, P = .71), and
procedural adverse events (28% versus 30%, P = 1.00). However, in patients
treated with the ERIC device, thrombectomy procedures were less time-consuming
(67 versus 98 minutes, P = .009) and a rescue device was needed less often (18%
versus 39%, P = .02) compared with classic stent retrievers. CONCLUSIONS:
Mechanical thrombectomy with the ERIC device is effective and safe. Rates of
favorable procedural and clinical outcomes are at least as good as those with
classic stent retrievers. Of note, the ERIC device might be time-saving and
decrease the need for rescue devices. These promising results call for
replication in larger prospective clinical trials.
PMID- 28495949
TI - The Central Bright Spot Sign: A Potential New MR Imaging Sign for the Early
Diagnosis of Anterior Ischemic Optic Neuropathy due to Giant Cell Arteritis.
AB - BACKGROUND AND PURPOSE: A rapid identification of the etiology of anterior
ischemic optic neuropathy is crucial because it determines therapeutic
management. Our aim was to assess MR imaging to study the optic nerve head in
patients referred with anterior ischemic optic neuropathy, due to either giant
cell arteritis or the nonarteritic form of the disease, compared with healthy
subjects. MATERIALS AND METHODS: Fifteen patients with giant cell arteritis
related anterior ischemic optic neuropathy and 15 patients with nonarteritic
anterior ischemic optic neuropathy from 2 medical centers were prospectively
included in our study between August 2015 and May 2016. Fifteen healthy subjects
and patients had undergone contrast-enhanced, flow-compensated, 3D T1-weighted MR
imaging. The bright spot sign was defined as optic nerve head enhancement with a
3-grade ranking system. Two radiologists and 1 ophthalmologist independently
performed blinded evaluations of MR imaging sequences with this scale.
Statistical analysis included interobserver agreement. RESULTS: MR imaging scores
were significantly higher in patients with giant cell arteritis-related anterior
ischemic optic neuropathy than in patients with nonarteritic anterior ischemic
optic neuropathy (P <= .05). All patients with giant cell arteritis-related
anterior ischemic optic neuropathy (15/15) and 7/15 patients with nonarteritic
anterior ischemic optic neuropathy presented with the bright spot sign. No
healthy subjects exhibited enhancement of the anterior part of the optic nerve.
There was a significant relationship between the side of the bright spot and the
side of the anterior ischemic optic neuropathy (P <= .001). Interreader agreement
was good for observers (kappa = 0.815). CONCLUSIONS: Here, we provide evidence of
a new MR imaging sign that identifies the acute stage of giant cell arteritis
related anterior ischemic optic neuropathy; patients without this central bright
spot sign always had a nonarteritic pathophysiology and therefore did not require
emergency corticosteroid therapy.
PMID- 28495950
TI - Carotid Bulb Webs as a Cause of "Cryptogenic" Ischemic Stroke.
AB - BACKGROUND AND PURPOSE: Carotid webs are intraluminal shelf-like filling defects
at the carotid bulb with recently recognized implications in patients with
recurrent ischemic stroke. We sought to determine whether carotid webs are an
under-recognized cause of "cryptogenic" ischemic stroke and to estimate their
prevalence in the general population. MATERIALS AND METHODS: A retrospective
review of neck CTA studies in young patients with cryptogenic stroke over the
past 6 years (n = 33) was performed to determine the prevalence of carotid webs
compared with a control group of patients who received neck CTA studies for
reasons other than ischemic stroke (n = 63). RESULTS: The prevalence of carotid
webs in the cryptogenic stroke population was 21.2% (95% CI, 8.9%-38.9%).
Patients with symptomatic carotid webs had a mean age of 38.9 years (range, 30-48
years) and were mostly African American (86%) and women (86%). In contrast, only
1.6% (95% CI, 0%-8.5%) of patients in the control group demonstrated a web. Our
findings demonstrate a statistically significant association between carotid webs
and ischemic stroke (OR = 16.7; 95% CI, 2.78-320.3; P = .01). CONCLUSIONS:
Carotid webs exhibit a strong association with ischemic stroke, and their
presence should be suspected in patients lacking other risk factors, particularly
African American women.
PMID- 28495951
TI - Biochemical analysis of cerebrospinal fluid in the laboratories of deployed
medical treatment facilities: are Multistix 10 SG strip and iSTAT useful?
AB - INTRODUCTION: During military deployment, the diagnosis and the management of
acute bacterial meningitis can be problematic, as deployed Medical Treatment
Facilities (MTFs) often have a limited laboratory diagnostic capability. However,
French Role 2 and 3 MTFs have point-of-care (POC) testing to perform urinary
(Multistix 10 SG strip) and blood (iSTAT handheld analyser) biochemical testing
mentioned in AMedP8.5. The purpose of this study was to compare the accuracy of
this urine test strip and of the iSTAT CHEM8 and CG4 cartridges with a standard
hospital bench top analyser in order to determine if these POC devices have a
potential role in the biochemical analysis of cerebrospinal fluid (CSF protein,
CSF glucose and CSF lactate, respectively). METHODS: Agreement between the index
methods and the reference methods (suitable kits on the Cobas 6 000 System) was
evaluated by parallel testing of 30 CSF samples by both techniques. For CSF
protein, agreement between the strip and the reference method was evaluated
determining the kappa coefficient. For CSF glucose and CSF lactate subgroups,
least squares linear regressions were calculated and Bland-Altman analyses were
performed. RESULTS: The Multistix 10 SG strip can be used to make a
semiquantitative determination of CSF protein. A good agreement between the strip
and the reference method was observed (kappa coefficient: 0.93 (IC95 0.82 to 1)).
This strip is thus well adapted to demonstrate an elevation of CSF protein level
as observed in acute bacterial meningitis. The iSTAT CHEM8 and CG4+ cartridges
correlated well with the reference methods for the determination of CSF glucose
and CSF lactate, respectively (r2>0.98) but exhibited a negative bias (~ -7% and
~ -15%, respectively). CONCLUSIONS: The combined use of the Multistix 10 SG strip
and of the iSTAT system appears to be an attractive solution for the biochemical
investigation of CSF in medical treatment facilities with limited laboratory
diagnostic capability.
PMID- 28495952
TI - Deep and profound hypothermia in haemorrhagic shock, friend or foe? A systematic
review.
AB - INTRODUCTION: Survival in exsanguinating cardiac arrest patients is poor, as is
neurological outcome in survivors. Hypothermia has traditionally been seen as
harmful to trauma patients and associated with increased mortality; however,
there has been speculation that cooling to very low temperatures (<=20 degrees C)
could be used to treat haemorrhagic trauma patients by the induction of a
suspended animation period through extreme cooling, which improves survival and
preserves neurological function. This has been termed emergency preservation and
resuscitation (EPR). METHODS: A systematic review of the literature was used to
examine the evidence base behind the use of deep and profound hypothermia in
haemorrhagic shock (HS). It included original research articles (human or animal)
with cooling to <=20 degrees C after HS or an experimental model replicating it.
Normovolaemic cardiac arrest, central nervous system injury and non-HS models
were excluded. RESULTS: Twenty articles using 456 animal subjects were included,
in which 327 were cooled to <=20 degrees C. All studies describing good survival
rates were possible using EPR and 19/20 demonstrated that EPR can preserve
neurological function after prolonged periods of circulatory arrest or minimal
circulatory flow. This additional period can be used for surgical intervention to
arrest haemorrhage in HS that would otherwise be lethal. CONCLUSIONS: The
outcomes of this review have significant implications for application to human
patients and the ongoing human clinical trial (EPR for Cardiac Arrest from
Trauma). Current evidence suggests that hypothermia <=20 degrees C used in the
form of EPR could be beneficial to the HS patient.
PMID- 28495954
TI - The Heavy Heart: Metabolic Mechanisms and Myocardial Mechanics.
PMID- 28495955
TI - Anisakiasis: a growing cause of abdominal pain!
PMID- 28495953
TI - Cardiometabolic Traits and Systolic Mechanics in the Community.
AB - BACKGROUND: Obesity and cardiometabolic dysfunction are associated with increased
risk of heart failure and other cardiovascular diseases. We sought to examine the
association of cardiometabolic traits with left ventricular (LV) cardiac
mechanics. We hypothesized that specific obesity-related phenotypes are
associated with distinct aspects of LV strain. METHODS AND RESULTS: We evaluated
the associations of obesity-related phenotypes, including central adiposity,
diabetes mellitus, insulin resistance, and circulating adipokine concentrations
with echocardiographic measures of LV mechanical function among participants of
the Framingham Heart Study Offspring and Third Generation cohorts. Among 6231
participants, the mean age was 51+/-16 years, and 54% were women. Greater body
mass index was associated with worse LV longitudinal strain, radial strain
(apical view), and longitudinal synchrony (multivariable-adjusted P<0.0001).
After accounting for body mass index, we found that central adiposity, as
measured by waist circumference, was associated with worse global longitudinal
strain and synchrony (P<=0.006). Measures of insulin resistance, dyslipidemia,
and diabetes mellitus also were associated with distinct aspects of LV mechanical
function. Circulating leptin concentrations were associated with global
longitudinal and radial strain (apical view, P<0.0001), whereas no such
association was found with leptin receptor, adiponectin, or C-reactive protein.
CONCLUSIONS: Our findings highlight the association of central obesity and
related cardiometabolic phenotypes above and beyond body mass index with
subclinical measures of LV mechanical function. Interestingly, obesity-related
traits were associated with distinct aspects of LV mechanics, underscoring
potential differential effects along specific LV planes of deformation. These
findings may shed light onto obesity-related cardiac remodeling and heart
failure.
PMID- 28495956
TI - Sharing of Genes and Pathways Across Complex Phenotypes: A Multilevel Genome-Wide
Analysis.
AB - Evidence from genome-wide association studies (GWAS) suggest that pleiotropic
effects on human complex phenotypes are very common. Recently, an atlas of
genetic correlations among complex phenotypes has broadened our understanding of
human diseases and traits. Here, we examine genetic overlap, from a gene-centric
perspective, among the same 24 phenotypes previously investigated for genetic
correlations. After adopting the multilevel pipeline (freely available at
http://grass.cgs.hku.hk/limx/kgg/), which includes intragenic single nucleotide
polymorphisms (SNPs), genes, and gene-sets, to estimate genetic similarities
across phenotypes, a large amount of sharing of several biologically related
phenotypes was confirmed. In addition, significant genetic overlaps were also
found among phenotype pairs that were previously unidentified by SNP-level
approaches. All these pairs with new genetic links are supported by earlier
epidemiological evidence, although only a few of them have pleiotropic genes in
the GWAS Catalog. Hence, our gene and gene-set analyses are able to provide new
insights into cross-phenotype connections. The investigation on genetic sharing
at three different levels presents a complementary picture of how common DNA
sequence variations contribute to disease comorbidities and trait manifestations.
PMID- 28495957
TI - Resolving the Complex Genetic Basis of Phenotypic Variation and Variability of
Cellular Growth.
AB - In all organisms, the majority of traits vary continuously between individuals.
Explaining the genetic basis of quantitative trait variation requires
comprehensively accounting for genetic and nongenetic factors as well as their
interactions. The growth of microbial cells can be characterized by a lag
duration, an exponential growth phase, and a stationary phase. Parameters that
characterize these growth phases can vary among genotypes (phenotypic variation),
environmental conditions (phenotypic plasticity), and among isogenic cells in a
given environment (phenotypic variability). We used a high-throughput microscopy
assay to map genetic loci determining variation in lag duration and exponential
growth rate in growth rate-limiting and nonlimiting glucose concentrations, using
segregants from a cross of two natural isolates of the budding yeast,
Saccharomyces cerevisiae We find that some quantitative trait loci (QTL) are
common between traits and environments whereas some are unique, exhibiting gene
by-environment interactions. Furthermore, whereas variation in the central
tendency of growth rate or lag duration is explained by many additive loci,
differences in phenotypic variability are primarily the result of genetic
interactions. We used bulk segregant mapping to increase QTL resolution by
performing whole-genome sequencing of complex mixtures of an advanced intercross
mapping population grown in selective conditions using glucose-limited
chemostats. We find that sequence variation in the high-affinity glucose
transporter HXT7 contributes to variation in growth rate and lag duration. Allele
replacements of the entire locus, as well as of a single polymorphic amino acid,
reveal that the effect of variation in HXT7 depends on genetic, and allelic,
background. Amplifications of HXT7 are frequently selected in experimental
evolution in glucose-limited environments, but we find that HXT7 amplifications
result in antagonistic pleiotropy that is absent in naturally occurring variants
of HXT7 Our study highlights the complex nature of the genotype-to-phenotype map
within and between environments.
PMID- 28495958
TI - Maternal Torso-Like Coordinates Tissue Folding During Drosophila Gastrulation.
AB - The rapid and orderly folding of epithelial tissue during developmental processes
such as gastrulation requires the precise coordination of changes in cell shape.
Here, we report that the perforin-like protein Torso-like (Tsl), the key
extracellular determinant for Drosophila embryonic terminal patterning, also
functions to control epithelial morphogenesis. We find that tsl null mutants
display a ventral cuticular hole phenotype that is independent of the loss of
terminal structures, and arises as a consequence of mesoderm invagination
defects. We show that the holes are caused by uncoordinated constriction of
ventral cell apices, resulting in the formation of an incomplete ventral furrow.
Consistent with these data, we find that loss of tsl is sensitive to gene dosage
of RhoGEF2, a critical mediator of Rho1-dependent ventral cell shape changes
during furrow formation, suggesting that Tsl may act in this pathway. In
addition, loss of tsl strongly suppressed the effects of ectopic expression of
Folded Gastrulation (Fog), a secreted protein that promotes apical constriction.
Taken together, our data suggest that Tsl controls Rho1-mediated apical
constriction via Fog. Therefore, we propose that Tsl regulates extracellular Fog
activity to synchronize cell shape changes and coordinate ventral morphogenesis
in Drosophila Identifying the Tsl-mediated event that is common to both terminal
patterning and morphogenesis will be valuable for our understanding of the
extracellular control of developmental signaling by perforin-like proteins.
PMID- 28495959
TI - Potential Nematode Alarm Pheromone Induces Acute Avoidance in Caenorhabditis
elegans.
AB - It is crucial for animal survival to detect dangers such as predators. A good
indicator of dangers is injury of conspecifics. Here we show that fluids released
from injured conspecifics invoke acute avoidance in both free-living and
parasitic nematodes. Caenorhabditis elegans avoids extracts from closely related
nematode species but not fruit fly larvae. The worm extracts have no impact on
animal lifespan, suggesting that the worm extract may function as an alarm
instead of inflicting physical harm. Avoidance of the worm extract requires the
function of a cGMP signaling pathway that includes the cGMP-gated channel TAX
2/TAX-4 in the amphid sensory neurons ASI and ASK. Genetic evidence indicates
that the avoidance behavior is modulated by the neurotransmitters GABA and
serotonin, two common targets of anxiolytic drugs. Together, these data support a
model that nematodes use a nematode-specific alarm pheromone to detect
conspecific injury.
PMID- 28495960
TI - Inferring the Joint Demographic History of Multiple Populations: Beyond the
Diffusion Approximation.
AB - Understanding variation in allele frequencies across populations is a central
goal of population genetics. Classical models for the distribution of allele
frequencies, using forward simulation, coalescent theory, or the diffusion
approximation, have been applied extensively for demographic inference, medical
study design, and evolutionary studies. Here we propose a tractable model of
ordinary differential equations for the evolution of allele frequencies that is
closely related to the diffusion approximation but avoids many of its limitations
and approximations. We show that the approach is typically faster, more
numerically stable, and more easily generalizable than the state-of-the-art
software implementation of the diffusion approximation. We present a number of
applications to human sequence data, including demographic inference with a five
population joint frequency spectrum and a discussion of the robustness of the out
of-Africa model inference to the choice of modern population.
PMID- 28495961
TI - An Evolutionarily Conserved Role of Presenilin in Neuronal Protection in the
Aging Drosophila Brain.
AB - Mutations in the Presenilin genes are the major genetic cause of Alzheimer's
disease. Presenilin and Nicastrin are essential components of gamma-secretase, a
multi-subunit protease that cleaves Type I transmembrane proteins. Genetic
studies in mice previously demonstrated that conditional inactivation of
Presenilin or Nicastrin in excitatory neurons of the postnatal forebrain results
in memory deficits, synaptic impairment, and age-dependent neurodegeneration. The
roles of Drosophila Presenilin (Psn) and Nicastrin (Nct) in the adult fly brain,
however, are unknown. To knockdown (KD) Psn or Nct selectively in neurons of the
adult brain, we generated multiple shRNA lines. Using a ubiquitous driver, these
shRNA lines resulted in 80-90% reduction of mRNA and pupal lethality-a phenotype
that is shared with Psn and Nct mutants carrying nonsense mutations. Furthermore,
expression of these shRNAs in the wing disc caused notching wing phenotypes,
which are also shared with Psn and Nct mutants. Similar to Nct, neuron-specific
Psn KD using two independent shRNA lines led to early mortality and rough eye
phenotypes, which were rescued by a fly Psn transgene. Interestingly, conditional
KD (cKD) of Psn or Nct in adult neurons using the elav-Gal4 and tubulin-Gal80ts
system caused shortened lifespan, climbing defects, increases in apoptosis, and
age-dependent neurodegeneration. Together, these findings demonstrate that,
similar to their mammalian counterparts, Drosophila Psn and Nct are required for
neuronal survival during aging and normal lifespan, highlighting an
evolutionarily conserved role of Presenilin in neuronal protection in the aging
brain.
PMID- 28495962
TI - Dietary supplementation of heat-treated Gracilaria and Ulva seaweeds enhanced
acute hypoxia tolerance in gilthead sea bream (Sparus aurata).
AB - Intensive aquaculture practices involve rearing fish at high densities. In these
conditions, fish may be exposed to suboptimal dissolved O2 levels with an
increased formation of reactive O2 species (ROS) in tissues. Seaweeds (SW)
contain biologically active substances with efficient antioxidant capacities.
This study evaluated the effects of dietary supplementation of heat-treated SW
(5% Gracilaria vermiculophylla or 5% Ulva lactuca) on stress bioindicators in sea
bream subjected to a hypoxic challenge. 168 fish (104.5 g average weight) were
distributed in 24 tanks, in which eight tanks were fed one of three experimental
diets for 34 days: (i) a control diet without SW supplementation, (ii) a control
diet supplemented with Ulva, or (iii) a control diet with Gracilaria Thereafter,
fish from 12 tanks (n=4 tanks/dietary treatment) were subjected to 24 h hypoxia
(1.3 mg O2 l-1) and subsequent recovery normoxia (8.6 mg O2 l-1). Hypoxic fish
showed an increase in hematocrit values regardless of dietary treatment. Dietary
modulation of the O2-carrying capacity was conspicuous during recovery, as fish
fed SW supplemented diets displayed significantly higher haemoglobin
concentration than fish fed the control diet. After the challenge, survival rates
in both groups of fish fed SW were higher, which was consistent with a decrease
in hepatic lipid peroxidation in these groups. Furthermore, the hepatic
antioxidant enzyme activities were modulated differently by changes in
environmental O2 condition, particularly in sea bream fed the Gracilaria diet.
After being subjected to hypoxia, the gene expression of antioxidant enzymes and
molecular chaperones in liver and heart were down regulated in sea bream fed SW
diets. This study suggests that the antioxidant properties of heat-treated SW may
have a protective role against oxidative stress. The nature of these compounds
and possible mechanisms implied are currently being investigated.
PMID- 28495963
TI - Arabidopsis DNA topoisomerase I alpha is required for adaptive response to light
and flower development.
AB - DNA topoisomerase I alpha (TOP1alpha) plays a specific role in Arabidopsis
thaliana development and is required for stem cell regulation in shoot and floral
meristems. Recently, a new role independent of meristem functioning has been
described for TOP1alpha, namely flowering time regulation. The same feature had
been detected by us earlier for fas5, a mutant allele of TOP1alpha In this study
we clarify the effects of fas5 on bolting initiation and analyze the molecular
basis of its role on flowering time regulation. We show that fas5 mutation leads
to a constitutive shade avoidance syndrome, accompanied by leaf hyponasty,
petiole elongation, lighter leaf color and early bolting. Other alleles of
TOP1alpha demonstrate the same shade avoidance response. RNA sequencing confirmed
the activation of shade avoidance gene pathways in fas5 mutant plants. It also
revealed the repression of many genes controlling floral meristem identity and
organ morphogenesis. Our research further expands the knowledge of TOP1alpha
function in plant development and reveals that besides stem cell maintenance
TOP1alpha plays an important new role in regulating the adaptive plant response
to light stimulus and flower development.
PMID- 28495964
TI - Transition zone cells reach G2 phase before initiating elongation in maize root
apex.
AB - Root elongation requires cell divisions in the meristematic zone and cell
elongation in the elongation zone. The boundary between dividing and elongating
cells is called the transition zone. In the meristem zone, initial cells are
continuously dividing, but on the basal side of the meristem cells exit the
meristem through the transition zone and enter in the elongation zone, where they
stop division and rapidly elongate. Throughout this journey cells are accompanied
by changes in cell cycle progression. Flow cytometry analysis showed that
meristematic cells are in cycle, but exit when they enter the elongation zone. In
addition, the percentage of cells in G2 phase (4C) strongly increased from the
meristem to the elongation zone. However, we did not observe remarkable changes
in the percentage of cells in cell cycle phases along the entire elongation zone.
These results suggest that meristematic cells in maize root apex stop the cell
cycle in G2 phase after leaving the meristem.
PMID- 28495965
TI - Pias3 is necessary for dorso-ventral patterning and visual response of retinal
cones but is not required for rod photoreceptor differentiation.
AB - Protein inhibitor of activated Stat 3 (Pias3) is implicated in guiding
specification of rod and cone photoreceptors through post-translational
modification of key retinal transcription factors. To investigate its role during
retinal development, we deleted exon 2-5 of the mouse Pias3 gene, which resulted
in complete loss of the Pias3 protein. Pias3-/- mice did not show any overt
phenotype, and retinal lamination appeared normal even at 18 months. We detected
reduced photopic b-wave amplitude by electroretinography following green light
stimulation of postnatal day (P)21 Pias3-/- retina, suggesting a compromised
visual response of medium wavelength (M) cones. No change was evident in response
of short wavelength (S) cones or rod photoreceptors until 7 months. Increased S
opsin expression in the M-cone dominant dorsal retina suggested altered
distribution of cone photoreceptors. Transcriptome profiling of P21 and 18-month
old Pias3-/- retina revealed aberrant expression of a subset of photoreceptor
genes. Our studies demonstrate functional redundancy in SUMOylation-associated
transcriptional control mechanisms and identify a specific, though limited, role
of Pias3 in modulating spatial patterning and optimal function of cone
photoreceptor subtypes in the mouse retina.
PMID- 28495966
TI - Lynn Margulis and the endosymbiont hypothesis: 50 years later.
AB - The 1967 article "On the Origin of Mitosing Cells" in the Journal of Theoretical
Biology by Lynn Margulis (then Lynn Sagan) is widely regarded as stimulating
renewed interest in the long-dormant endosymbiont hypothesis of organelle
origins. In her article, not only did Margulis champion an endosymbiotic origin
of mitochondria and plastids from bacterial ancestors, but she also posited that
the eukaryotic flagellum (undulipodium in her usage) and mitotic apparatus
originated from an endosymbiotic, spirochete-like organism. In essence, she
presented a comprehensive symbiotic view of eukaryotic cell evolution
(eukaryogenesis). Not all of the ideas in her article have been accepted, for
want of compelling evidence, but her vigorous promotion of the role of symbiosis
in cell evolution unquestionably had a major influence on how subsequent
investigators have viewed the origin and evolution of mitochondria and plastids
and the eukaryotic cell per se.
PMID- 28495967
TI - Streptococcus pneumoniae capsular polysaccharide is linked to peptidoglycan via a
direct glycosidic bond to beta-D-N-acetylglucosamine.
AB - For many bacteria, including those important in pathogenesis, expression of a
surface-localized capsular polysaccharide (CPS) can be critical for survival in
host environments. In Gram-positive bacteria, CPS linkage is to either the
cytoplasmic membrane or the cell wall. Despite the frequent occurrence and
essentiality of these polymers, the exact nature of the cell wall linkage has not
been described in any bacterial species. Using the Streptococcus pneumoniae
serotype 2 CPS, which is synthesized by the widespread Wzy mechanism, we found
that linkage occurs via the reducing end glucose of CPS and the beta-D-N
acetylglucosamine (GlcNAc) residues of peptidoglycan (PG). Hydrofluoric acid
resistance, 31P-NMR, and 32P labeling demonstrated the lack of phosphodiester
bonds, which typically occur in PG-polysaccharide linkages. Component sugar
analysis of purified CPS-PG identified only CPS and PG sugars in the appropriate
ratios, suggesting the absence of an oligosaccharide linker. Time of flight mass
spectrometry confirmed a direct glycosidic linkage between CPS and PG and showed
that a single CPS repeat unit can be transferred to PG. The linkage was
acetolysis susceptible, indicative of a 1,6 glycosidic bond between CPS and the
GlcNAc C-6. The acetylation state of GlcNAc did not affect linkage. A direct
glycosidic linkage to PG was also demonstrated for serotypes 8 and 31, whose
reducing end sugars are glucose and galactose, respectively. These results
provide the most detailed descriptions of CPS-PG linkages for any microorganism.
Identification of the linkage is a first step toward identifying the linking
enzyme and potential inhibitors of its activity.
PMID- 28495968
TI - Laboratory measurements of HDO/H2O isotopic fractionation during ice deposition
in simulated cirrus clouds.
AB - The stable isotopologues of water have been used in atmospheric and climate
studies for over 50 years, because their strong temperature-dependent
preferential condensation makes them useful diagnostics of the hydrological
cycle. However, the degree of preferential condensation between vapor and ice has
never been directly measured at temperatures below 233 K (-40 degrees C),
conditions necessary to form cirrus clouds in the Earth's atmosphere, routinely
observed in polar regions, and typical for the near-surface atmospheric layers of
Mars. Models generally assume an extrapolation from the warmer experiments of
Merlivat and Nief [Merlivat L, Nief G (1967) Tellus 19:122-127]. Nonequilibrium
kinetic effects that should alter preferential partitioning have also not been
well characterized experimentally. We present here direct measurements of HDO/H2O
equilibrium fractionation between vapor and ice ([Formula: see text]) at cirrus
relevant temperatures, using in situ spectroscopic measurements of the evolving
isotopic composition of water vapor during cirrus formation experiments in a
cloud chamber. We rule out the recent proposed upward modification of [Formula:
see text], and find values slightly lower than Merlivat and Nief. These
experiments also allow us to make a quantitative validation of the kinetic
modification expected to occur in supersaturated conditions in the ice-vapor
system. In a subset of diffusion-limited experiments, we show that kinetic
isotope effects are indeed consistent with published models, including allowing
for small surface effects. These results are fundamental for inferring processes
on Earth and other planets from water isotopic measurements. They also
demonstrate the utility of dynamic in situ experiments for studying fractionation
in geochemical systems.
PMID- 28495969
TI - Fold-change detection and scale invariance of cell-cell signaling in social
amoeba.
AB - Cell-cell signaling is subject to variability in the extracellular volume, cell
number, and dilution that potentially increase uncertainty in the absolute
concentrations of the extracellular signaling molecules. To direct cell
aggregation, the social amoebae Dictyostelium discoideum collectively give rise
to oscillations and waves of cyclic adenosine 3',5'-monophosphate (cAMP) under a
wide range of cell density. To date, the systems-level mechanism underlying the
robustness is unclear. By using quantitative live-cell imaging, here we show that
the magnitude of the cAMP relay response of individual cells is determined by
fold change in the extracellular cAMP concentrations. The range of cell density
and exogenous cAMP concentrations that support oscillations at the population
level agrees well with conditions that support a large fold-change-dependent
response at the single-cell level. Mathematical analysis suggests that invariance
of the oscillations to density transformation is a natural outcome of combining
secrete-and-sense systems with a fold-change detection mechanism.
PMID- 28495970
TI - High-throughput biochemical profiling reveals sequence determinants of dCas9 off
target binding and unbinding.
AB - The bacterial adaptive immune system CRISPR-Cas9 has been appropriated as a
versatile tool for editing genomes, controlling gene expression, and visualizing
genetic loci. To analyze Cas9's ability to bind DNA rapidly and specifically, we
generated multiple libraries of potential binding partners for measuring the
kinetics of nuclease-dead Cas9 (dCas9) interactions. Using a massively parallel
method to quantify protein-DNA interactions on a high-throughput sequencing flow
cell, we comprehensively assess the effects of combinatorial mismatches between
guide RNA (gRNA) and target nucleotides, both in the seed and in more distal
nucleotides, plus disruption of the protospacer adjacent motif (PAM). We report
two consequences of PAM-distal mismatches: reversal of dCas9 binding at long time
scales, and synergistic changes in association kinetics when other gRNA-target
mismatches are present. Together, these observations support a model for Cas9
specificity wherein gRNA-DNA mismatches at PAM-distal bases modulate different
biophysical parameters that determine association and dissociation rates. The
methods we present decouple aspects of kinetic and thermodynamic properties of
the Cas9-DNA interaction and broaden the toolkit for investigating off-target
binding behavior.
PMID- 28495971
TI - Cilia- and Flagella-Associated Protein 69 Regulates Olfactory Transduction
Kinetics in Mice.
AB - Animals detect odorous chemicals through specialized olfactory sensory neurons
(OSNs) that transduce odorants into neural electrical signals. We identified a
novel and evolutionarily conserved protein, cilia- and flagella-associated
protein 69 (CFAP69), in mice that regulates olfactory transduction kinetics. In
the olfactory epithelium, CFAP69 is enriched in OSN cilia, where olfactory
transduction occurs. Bioinformatic analysis suggests that a large portion of
CFAP69 can form Armadillo-type alpha-helical repeats, which may mediate protein
protein interactions. OSNs lacking CFAP69, remarkably, displayed faster kinetics
in both the on and off phases of electrophysiological responses at both the
neuronal ensemble level as observed by electroolfactogram and the single-cell
level as observed by single-cell suction pipette recordings. In single-cell
analysis, OSNs lacking CFAP69 showed faster response integration and were able to
fire APs more faithfully to repeated odor stimuli. Furthermore, both male and
female mutant mice that specifically lack CFAP69 in OSNs exhibited attenuated
performance in a buried food pellet test when a background of the same odor to
the food pellet was present even though they should have better temporal
resolution of coding olfactory stimulation at the peripheral. Therefore, the role
of CFAP69 in the olfactory system seems to be to allow the olfactory transduction
machinery to work at a precisely regulated range of response kinetics for robust
olfactory behavior.SIGNIFICANCE STATEMENT Sensory receptor cells are generally
thought to evolve to respond to sensory cues as fast as they can. This idea is
consistent with mutational analyses in various sensory systems, where mutations
of sensory receptor cells often resulted in reduced response size and slowed
response kinetics. Contrary to this idea, we have found that there is a kinetic
"damper" present in the olfactory transduction cascade of the mouse that slows
down the response kinetics and, by doing so, it reduces the peripheral temporal
resolution in coding odor stimuli and allows for robust olfactory behavior. This
study should trigger a rethinking of the significance of the intrinsic speed of
sensory transduction and the pattern of the peripheral coding of sensory stimuli.
PMID- 28495972
TI - Multiple Transient Signals in Human Visual Cortex Associated with an Elementary
Decision.
AB - The cerebral cortex continuously undergoes changes in its state, which are
manifested in transient modulations of the cortical power spectrum. Cortical
state changes also occur at full wakefulness and during rapid cognitive acts,
such as perceptual decisions. Previous studies found a global modulation of beta
band (12-30 Hz) activity in human and monkey visual cortex during an elementary
visual decision: reporting the appearance or disappearance of salient visual
targets surrounded by a distractor. The previous studies disentangled neither the
motor action associated with behavioral report nor other secondary processes,
such as arousal, from perceptual decision processing per se. Here, we used
magnetoencephalography in humans to pinpoint the factors underlying the beta-band
modulation. We found that disappearances of a salient target were associated with
beta-band suppression, and target reappearances with beta-band enhancement. This
was true for both overt behavioral reports (immediate button presses) and silent
counting of the perceptual events. This finding indicates that the beta-band
modulation was unrelated to the execution of the motor act associated with a
behavioral report of the perceptual decision. Further, changes in pupil-linked
arousal, fixational eye movements, or gamma-band responses were not necessary for
the beta-band modulation. Together, our results suggest that the beta-band
modulation was a top-down signal associated with the process of converting graded
perceptual signals into a categorical format underlying flexible behavior. This
signal may have been fed back from brain regions involved in decision processing
to visual cortex, thus enforcing a "decision-consistent" cortical
state.SIGNIFICANCE STATEMENT Elementary visual decisions are associated with a
rapid state change in visual cortex, indexed by a modulation of neural activity
in the beta-frequency range. Such decisions are also followed by other events
that might affect the state of visual cortex, including the motor command
associated with the report of the decision, an increase in pupil-linked arousal,
fixational eye movements, and fluctuations in bottom-up sensory processing. Here,
we ruled out the necessity of these events for the beta-band modulation of visual
cortex. We propose that the modulation reflects a decision-related state change,
which is induced by the conversion of graded perceptual signals into a
categorical format underlying behavior. The resulting decision signal may be fed
back to visual cortex.
PMID- 28495973
TI - Contrasting the Role of xCT and GLT-1 Upregulation in the Ability of Ceftriaxone
to Attenuate the Cue-Induced Reinstatement of Cocaine Seeking and Normalize AMPA
Receptor Subunit Expression.
AB - Long-term treatment with ceftriaxone attenuates the reinstatement of cocaine
seeking while increasing the function of the glutamate transporter 1 (GLT-1) and
system xC- (Sxc) in the nucleus accumbens core (NAc). Sxc contributes the
majority of nonsynaptic extracellular glutamate in the NAc, while GLT-1 is
responsible for the majority of glutamate uptake. Here we used antisense to
decrease the expression of GLT-1 and xCT (a catalytic subunit of Sxc) to
determine the relative importance of both proteins in mediating the ability of
ceftriaxone to prevent cue-induced reinstatement of cocaine seeking and normalize
glutamatergic proteins in the NAc of rats. Intra-NAc xCT knockdown prevented
ceftriaxone from attenuating reinstatement and from upregulating GLT-1 and
resulted in increased surface expression of AMPA receptor subunits GluA1 and
GluA2. Intra-NAc GLT-1 knockdown also prevented ceftriaxone from attenuating
reinstatement and from upregulating xCT expression, without affecting GluA1 and
GluA2 expression. In the absence of cocaine or ceftriaxone treatment, xCT
knockdown in the NAc increased the expression of both GluA1 and GluA2 without
affecting GLT-1 expression while GLT-1 knockdown had no effect. PCR and
immunoprecipitation of GLT-1 revealed that ceftriaxone does not upregulate GLT-1
and xCT through a transcriptional mechanism, and their coregulation by
ceftriaxone is not mediated by physical interaction. These data support important
and distinct roles for xCT and GLT-1 in the actions of ceftriaxone and add to a
body of literature finding evidence for coregulation of these transporters. Our
results also point to xCT expression and subsequent basal glutamate levels as
being a key mediator of AMPA receptor expression in the NAc.SIGNIFICANCE
STATEMENT Ceftriaxone attenuates the reinstatement of cocaine, alcohol, and
heroin seeking. The mechanism of action of this behavioral effect has been
attributed to glutamate transporter 1 (GLT-1) and xCT (a catalytic subunit of
Sxc)/Sxc upregulation in the nucleus accumbens core. Here we used an antisense
strategy to knock down GLT-1 or xCT in the nucleus accumbens core and examined
the behavioral and molecular consequences. While upregulation of both xCT and GLT
1 are essential to the ability of ceftriaxone to attenuate cue-induced
reinstatement of cocaine seeking, each protein uniquely affects the expression of
other glutamate receptor and transporter proteins. We also report that reducing
basal glutamate levels through the manipulation of xCT expression increases the
surface expression of AMPA receptor subunits, providing insight to the mechanism
by which cocaine alters AMPA surface expression.
PMID- 28495974
TI - Long-Term Depression of Intrinsic Excitability Accompanied by Synaptic Depression
in Cerebellar Purkinje Cells.
AB - Long-term depression (LTD) at the parallel fiber (PF)-to-cerebellar Purkinje cell
(PC) synapse is implicated in the output of PCs, the sole output of the
cerebellar cortex. In addition to synaptic plasticity, intrinsic excitability is
also one of the components that determines PC output. Although long-term
potentiation of intrinsic excitability (LTP-IE) has been suggested, it has yet to
be investigated how PF-PC LTD modifies intrinsic excitability of PCs. Here, we
show that pairing of the PF and climbing fiber (CF) for PF-PC LTD induction
evokes LTD-IE in cerebellar PCs from male C57BL/6 mice. Interestingly, this
intrinsic plasticity showed different kinetics from synaptic plasticity, but both
forms of plasticity share Ca2+ signaling and protein kinase C pathway as their
underlying mechanism. Although small-conductance Ca2+-activated K+ channels play
important roles in LTP-IE, no direct implication has been found. After PF-PC LTD
induction, neither the temporal summation of dendritic EPSP nor the power of
spike frequency adaptation is changed, indicating that cerebellar LTD executes
the information processing in a quantitative way without quality changes of
synaptic integration and generation of output signals. Our results suggest that
LTD-IE may have a synergistic effect with synaptic depression on the total net
output of neurons by amplifying the modification of PF synaptic
transmission.SIGNIFICANCE STATEMENT Although the output of Purkinje cells (PCs)
is a critical component of cerebellum-dependent learning and memory, the changes
of PC excitability when synaptic LTD occurs are unclear. Here, we show that the
induction of PF-PC LTD evokes LTD-IE in PCs. Our observation complements previous
intrinsic plasticity phenomenon of long-term potentiation of intrinsic
excitability (LTP-IE), providing evidence for the idea that intrinsic plasticity
has bidirectionality as synaptic plasticity. LTD-IE occurs together with synaptic
LTD and both phenomena are dependent on the Ca2+ signaling pathway. Furthermore,
our findings raise the prospect that this synaptic and intrinsic plasticity acts
synergistically in PCs to modify neuronal activity in the same direction when
learning occurs.
PMID- 28495979
TI - Meet the First Authors.
PMID- 28495976
TI - Optogenetic Inhibition of Ventral Pallidum Neurons Impairs Context-Driven Salt
Seeking.
AB - Salt appetite, in which animals can immediately seek out salt when under a novel
state of sodium deprivation, is a classic example of how homeostatic systems
interface with learned associations to produce an on-the-fly updating of
motivated behavior. Neural activity in the ventral pallidum (VP) has been shown
to encode changes in the value of salt under such conditions, both the value of
salt itself (Tindell et al., 2006) and the motivational value of its predictive
cues (Tindell et al., 2009; Robinson and Berridge, 2013). However, it is not
known whether the VP is necessary for salt appetite in terms of seeking out salt
or consuming salt following sodium depletion. Here, we used a conditioned place
preference procedure to investigate the effects of optogenetically inhibiting the
VP on context-driven salt seeking and the consumption of salt following
deprivation. Male rats learned to associate one context with sucrose and another
context with less-desirable salt. Following sodium depletion, and in the absence
of either sucrose or salt, we found that inhibiting the VP selectively reduced
the elevation in time spent in the salt-paired context. VP inhibition had minimal
effects on the consumption of salt once it was made available. To our knowledge,
this is the first evidence that the VP or any brain region is necessary for the
ability to use contextual cues to guide salt seeking. These results highlight a
dissociation between deficit-driven reward seeking and reward consumption to
replenish those deficits, with the former process being particularly sensitive to
on-line VP activity.SIGNIFICANCE STATEMENT Salt appetite, in which rats will
immediately seek out a once-undesirable concentrated salt solution after being
depleted of bodily sodium despite never having tasted salt as a positive reward,
is a phenomenon showing how animals can update their motivational goals without
any new learning or conditioning. This salt-seeking behavior is also observed
when the animal is presented with salt-paired cues. The neural circuitry
necessary for context-driven salt-seeking behavior is unknown. We used a novel
conditioned place preference procedure to show that optogenetic inhibition of the
ventral pallidum (VP), a region known for processing reward, impairs context
driven salt seeking and has minimal effects on the consumption of salt itself
following sodium depletion. These results highlight the importance of the VP in
context-driven reward-seeking behavior.
PMID- 28495975
TI - Short-Term Depression of Sprouted Mossy Fiber Synapses from Adult-Born Granule
Cells.
AB - Epileptic seizures potently modulate hippocampal adult neurogenesis, and adult
born dentate granule cells contribute to the pathologic retrograde sprouting of
mossy fiber axons, both hallmarks of temporal lobe epilepsy. The characteristics
of these sprouted synapses, however, have been largely unexplored, and the
specific contribution of adult-born granule cells to functional mossy fiber
sprouting is unknown, primarily due to technical barriers in isolating sprouted
mossy fiber synapses for analysis. Here, we used DcxCreERT2 transgenic mice to
permanently pulse-label age-defined cohorts of granule cells born either before
or after pilocarpine-induced status epilepticus (SE). Using optogenetics, we
demonstrate that adult-born granule cells born before SE form functional
recurrent monosynaptic excitatory connections with other granule cells.
Surprisingly, however, although healthy mossy fiber synapses in CA3 are well
characterized "detonator" synapses that potently drive postsynaptic cell firing
through their profound frequency-dependent facilitation, sprouted mossy fiber
synapses from adult-born cells exhibited profound frequency-dependent depression,
despite possessing some of the morphological hallmarks of mossy fiber terminals.
Mature granule cells also contributed to functional mossy fiber sprouting, but
exhibited less synaptic depression. Interestingly, granule cells born shortly
after SE did not form functional excitatory synapses, despite robust sprouting.
Our results suggest that, although sprouted mossy fibers form recurrent
excitatory circuits with some of the morphological characteristics of typical
mossy fiber terminals, the functional characteristics of sprouted synapses would
limit the contribution of adult-born granule cells to hippocampal
hyperexcitability in the epileptic hippocampus.SIGNIFICANCE STATEMENT In the
hippocampal dentate gyrus, seizures drive retrograde sprouting of granule cell
mossy fiber axons. We directly activated sprouted mossy fiber synapses from adult
born granule cells to study their synaptic properties. We reveal that sprouted
synapses from adult-born granule cells have a diminished ability to sustain
recurrent excitation in the epileptic hippocampus, which raises questions about
the role of sprouting and adult neurogenesis in sustaining seizure-like activity.
PMID- 28495977
TI - Modelling the implications of reducing smoking prevalence: the public health and
economic benefits of achieving a 'tobacco-free' UK.
AB - INTRODUCTION: Smoking is still the most preventable cause of cancer, and a
leading cause of premature mortality and health inequalities in the UK. This
study modelled the health and economic impacts of achieving a 'tobacco-free'
ambition (TFA) where, by 2035, less than 5% of the population smoke tobacco
across all socioeconomic groups. METHODS: A non-linear multivariate regression
model was fitted to cross-sectional smoking data to create projections to 2035.
These projections were used to predict the future incidence and costs of 17
smoking-related diseases using a microsimulation approach. The health and
economic impacts of achieving a TFA were evaluated against a predicted baseline
scenario, where current smoking trends continue. RESULTS: If trends continue, the
prevalence of smoking in the UK was projected to be 10% by 2035-well above a TFA.
If this ambition were achieved by 2035, it could mean 97 300 +/- 5 300 new cases
of smoking-related diseases are avoided by 2035 (tobacco-related cancers: 35
900+/- 4 100; chronic obstructive pulmonary disease: 29 000 +/- 2 700; stroke: 24
900 +/- 2 700; coronary heart disease: 7600 +/- 2 700), including around 12 350
diseases avoided in 2035 alone. The consequence of this health improvement is
predicted to avoid L67 +/- 8 million in direct National Health Service and social
care costs, and L548 million in non-health costs, in 2035 alone. CONCLUSION:
These findings strengthen the case to set bold targets on long-term declines in
smoking prevalence to achieve a tobacco 'endgame'. Results demonstrate the health
and economic benefits that meeting a TFA can achieve over just 20 years.
Effective ambitions and policy interventions are needed to reduce the disease and
economic burden of smoking.
PMID- 28495980
TI - Get Your Cell K.O. in the First Round.
PMID- 28495981
TI - Pacing Discovery: G-Protein beta Subunit Mutations in Sinus Node Dysfunction.
PMID- 28495982
TI - A New Role of Mister (MR) T in Hypertension: Mineralocorticoid Receptor, Immune
System, and Hypertension.
PMID- 28495983
TI - Immunomodulation Is the Key to Cardiac Repair.
PMID- 28495984
TI - "Pound-Years": Effects on the Heart of Long-Term Exposure to Obesity.
PMID- 28495985
TI - Oliver Smithies, DPhil: 1925-2017.
PMID- 28495986
TI - PCSK9 Inhibition to Reduce Cardiovascular Risk: Tempering Expectations.
PMID- 28495987
TI - A Multidisciplinary and Multicultural Adventure: From Materials Engineering to
Cardiovascular Science.
PMID- 28495988
TI - Rong Tian: Finding What Feeds the Heart.
PMID- 28495990
TI - The Texas Heart Institute: Part 2-Working Toward the Next Breakthrough in
Cardiovascular Medicine.
PMID- 28495989
TI - The Texas Heart Institute: Part 1-An Historical Perspective.
PMID- 28495991
TI - It's 10 pm; Do You Know Where Your Data Are? Data Provenance, Curation, and
Storage.
PMID- 28495992
TI - Scientific Discovery, Contextual Factors, and Cardiometabolic Health Research:
Back to the Future.
PMID- 28495993
TI - Safe and Effective Cardiac Regenerative Therapy With Human-Induced Pluripotent
Stem Cells: How Should We Prepare Pure Cardiac Myocytes?
PMID- 28495994
TI - Methodological Guidelines to Study Extracellular Vesicles.
AB - Owing to the relationship between extracellular vesicles (EVs) and physiological
and pathological conditions, the interest in EVs is exponentially growing. EVs
hold high hopes for novel diagnostic and translational discoveries. This review
provides an expert-based update of recent advances in the methods to study EVs
and summarizes currently accepted considerations and recommendations from sample
collection to isolation, detection, and characterization of EVs. Common
misconceptions and methodological pitfalls are highlighted. Although EVs are
found in all body fluids, in this review, we will focus on EVs from human blood,
not only our most complex but also the most interesting body fluid for
cardiovascular research.
PMID- 28495995
TI - Extracellular Vesicles in Cardiovascular Disease: Potential Applications in
Diagnosis, Prognosis, and Epidemiology.
AB - Extracellular vesicles originate from diverse subcellular compartments and are
released in the extracellular space. By transferring their cargoes into target
cells and tissues, they now emerge as novel regulators of intercellular
communication between adjacent and remote cells. Because vesicle composition and
biological content are specific signatures of cellular activation and injury,
their potential as diagnostic and prognostic biomarkers has raised significant
interest in cardiovascular diseases. Characterization of circulating vesicles- or
nonvesicles-bound nucleic acids represents a valuable tool for diagnosing and
monitoring cardiovascular diseases, recently referred to as a liquid biopsy.
Circulating extracellular vesicles offer a noninvasive and almost continuous
access to circulating information on the disease state in epidemiological
investigations. Finally, genetic engineering and cell-specific application of
extracellular vesicles could display a novel therapeutic option for the treatment
of cardiovascular diseases. In this review, we summarize the current knowledge
about extracellular vesicles as diagnostic and prognostic biomarkers, as well as
their potential applications for longitudinal epidemiological studies in
cardiovascular diseases.
PMID- 28495997
TI - Extracellular Vesicles in Metabolic Syndrome.
AB - Metabolic syndrome defines a cluster of interrelated risk factors for
cardiovascular disease and diabetes mellitus. These factors include metabolic
abnormalities, such as hyperglycemia, elevated triglyceride levels, low high
density lipoprotein cholesterol levels, high blood pressure, and obesity, mainly
central adiposity. In this context, extracellular vesicles (EVs) may represent
novel effectors that might help to elucidate disease-specific pathways in
metabolic disease. Indeed, EVs (a terminology that encompasses microparticles,
exosomes, and apoptotic bodies) are emerging as a novel mean of cell-to-cell
communication in physiology and pathology because they represent a new way to
convey fundamental information between cells. These microstructures contain
proteins, lipids, and genetic information able to modify the phenotype and
function of the target cells. EVs carry specific markers of the cell of origin
that make possible monitoring their fluctuations in the circulation as potential
biomarkers inasmuch their circulating levels are increased in metabolic syndrome
patients. Because of the mixed components of EVs, the content or the number of
EVs derived from distinct cells of origin, the mode of cell stimulation, and the
ensuing mechanisms for their production, it is difficult to attribute specific
functions as drivers or biomarkers of diseases. This review reports recent data
of EVs from different origins, including endothelial, smooth muscle cells,
macrophages, hepatocytes, adipocytes, skeletal muscle, and finally, those from
microbiota as bioeffectors of message, leading to metabolic syndrome. Depicting
the complexity of the mechanisms involved in their functions reinforce the
hypothesis that EVs are valid biomarkers, and they represent targets that can be
harnessed for innovative therapeutic approaches.
PMID- 28495998
TI - Correction to: Experimental, Systems, and Computational Approaches to
Understanding the MicroRNA-Mediated Reparative Potential of Cardiac Progenitor
Cell-Derived Exosomes From Pediatric Patients.
PMID- 28495996
TI - Extracellular Vesicles in Angiogenesis.
AB - During the past decade, extracellular vesicles (EVs), which include apoptotic
bodies, microvesicles, and exosomes, have emerged as important players in cell-to
cell communication in normal physiology and pathological conditions. EVs
encapsulate and convey various bioactive molecules that are further transmitted
to neighboring or more distant cells, where they induce various signaling
cascades. The message delivered to the target cells is dependent on EV
composition, which, in turn, is determined by the cell of origin and the
surrounding microenvironment during EV biogenesis. Among their multifaceted role
in the modulation of biological responses, the involvement of EVs in vascular
development, growth, and maturation has been widely documented and their
potential therapeutic application in regenerative medicine or angiogenesis
related diseases is drawing increasing interest. EVs derived from various cell
types have the potential to deliver complex information to endothelial cells and
to induce either pro- or antiangiogenic signaling. As dynamic systems, in
response to changes in the microenvironment, EVs adapt their cargo composition to
fine-tune the process of blood vessel formation. This article reviews the current
knowledge on the role of microvesicles and exosomes from various cellular origins
in angiogenesis, with a particular emphasis on the underlying mechanisms, and
discusses the main challenges and prerequisites for their therapeutic
applications.
PMID- 28495999
TI - beta-Arrestin-Mediated Regulation of the Human Ether-a-go-go-Related Gene
Potassium Channel.
AB - The rapidly activating delayed rectifier K+ channel (IKr) is encoded by the human
ether-a-go-go-related gene (hERG), which is important for the repolarization of
the cardiac action potential. Mutations in hERG or drugs can impair the function
or decrease the expression level of hERG channels, leading to long QT syndrome.
Thus, it is important to understand hERG channel trafficking and its regulation.
For this purpose, G protein-coupled receptors (GPCRs), which regulate a vast
array of cellular processes, represent a useful route. The development of
designer GPCRs known as designer receptors exclusively activated by designer
drugs (DREADDs) has made it possible to dissect specific GPCR signaling pathways
in various cellular systems. In the present study, by expressing an arrestin
biased M3 muscarinic receptor-based DREADD (M3D-arr) in stable hERG-expressing
human embryonic kidney (HEK) cells, we demonstrate that beta-arrestin signaling
plays a role in hERG regulation. By exclusively activating M3D-arr using the
otherwise inert compound, clozapine-N-oxide, we found that M3D-arr activation
increased mature hERG expression and current. Within this paradigm, M3D-arr
recruited beta-arrestin-1 to the plasma membrane, and promoted phosphoinositide 3
kinase-dependent activation of protein kinase B (Akt). The activated Akt acted
through phosphatidylinositol 3-phosphate 5-kinase and Rab11 to facilitate hERG
recycling to the plasma membrane. Potential beta-arrestin signaling-mediated
increases in hERG and IKr were also observed in hERG-HEK cells as well as in
neonatal rat ventricular myocytes treated with the muscarinic agonist carbachol.
These findings provide novel insight into hERG trafficking and regulation.
PMID- 28496000
TI - Stratification according to recursive partitioning analysis predicts outcome in
newly diagnosed glioblastomas.
AB - Glioblastoma accounts for more than half of diffuse gliomas. The prognosis of
patients with glioblastoma remains poor despite comprehensive and intensive
treatments. Furthermore, the clinical significance of molecular parameters and
routinely available clinical variables for the prognosis prediction of
glioblastomas remains limited. The authors describe a novel model may help in
prognosis prediction and clinical management of glioblastoma patients. We
performed a recursive partitioning analysis to generate three independent
prognostic classes of 103 glioblastomas patients from TCGA dataset. Class I (MGMT
promoter methylated, age <58), class II (MGMT promoter methylation, age >=58;
MGMT promoter unmethylation, age <54, KPS >=70; MGMT promoter unmethylation, age
>59, KPS >=70), class III (MGMT promoter unmethylation, age 54-58, KPS >=70; MGMT
promoter unmethylation, KPS <70). Age, KPS and MGMT promoter methylation were the
most significant prognostic factors for overall survival. The results were
validated in CGGA dataset.This was the first study to combine various molecular
parameters and clinical factors into recursive partitioning analysis to predict
the prognosis of patients with glioblastomas. We included MGMT promoter
methylation in our study, which could give better suggestion to patients for
their chemotherapy. This clinical study will serve as the backbone for the future
incorporation of molecular prognostic markers currently in development. Thus, our
recursive partitioning analysis model for glioblastomas may aid in clinical
prognosis evaluation.
PMID- 28496001
TI - DDX11-AS1 as potential therapy targets for human hepatocellular carcinoma.
AB - Hepatocellular Carcinoma (HCC) is one of the most fatal cancers, whose incidence
and death rates are still rising. Here, we report the identification of long non
coding RNAs (IncRNAs) that associated with HCC progression and metabolism based
on the systematically analysis of large scale RNA-seq data from HCC patients. We
identified seven lncRNAs with high confidence which were highly related with
prognostic of HCC. Of note, three of them had quite different expression patterns
between the control samples and the patients, and their critical roles in cancer
progression were validated. We proposed that DDX11-AS1 play important role during
HCC oncogenesis and may serve as potential therapy target for HCC.
PMID- 28496002
TI - Risk of cancer in patients with heart failure who use digoxin: a 10-year follow
up study and cell-based verification.
AB - Heart failure (HF) is the leading cause of death in the world and digoxin remains
one of the oldest therapies for HF. However, its safety and efficacy have been
controversial since its initial use and there is uncertainty about its long-term
efficacy and safety. Recently, the repositioning of cardiac glycosides is to
function in anti-tumor activity via multiple working pathways. It is interesting
to compare the potential effects of digoxin in clinical patients and cell lines.
First, we analyze patient information retrieved from the National Health
Insurance Research database of Taiwan between January 1, 2000 and December 31,
2000. This retrospective study included a study cohort (1,219 patients) and a
comparison cohort. Our analytical data suggested that patients taking digoxin are
at an increased risk of cancers, including breast, liver, and lung cancers,
during the 10-year follow-up period. In contrast to the anti-tumor function of
digoxin, we further examined the potential pathway of digoxin via the cell-based
strategy using several breast cancer cell lines, including MCF-7, BT-474, MAD-MB
231, and ZR-75-1. Digoxin consistently exerted its cytotoxicity to these four
cell lines with various range of concentration. However, the proliferation of ZR
75-1 cells was the only cell lines induced by digoxin and the others were
dramatically suppressed by digoxin. The responsiveness of SRSF3 to digoxin might
be involved with cell-type differences. In summary, we combined a cohort study
for digoxin treatment for HF patients with a cell-based strategy that addresses
the translation issue, which revealed the complexity of personalized medicine.
PMID- 28496003
TI - Peiminine inhibits colorectal cancer cell proliferation by inducing apoptosis and
autophagy and modulating key metabolic pathways.
AB - Peiminine, a compound extracted from the bulbs of Fritillaria thunbergii and
traditionally used as a medication in China and other Asian countries, was
reported to inhibit colorectal cancer cell proliferation and tumor growth by
inducing autophagic cell death. However, its mechanism of anticancer action is
not well understood, especially at the metabolic level, which was thought to
primarily account for peiminine's efficacy against cancer. Using an established
metabolomic profiling platform combining ultra-performance liquid
chromatography/tandem mass spectrometry with gas chromatography/mass
spectrometry, we identified metabolic alterations in colorectal cancer cell line
HCT-116 after peiminine treatment. Among the identified 236 metabolites, the
levels of 57 of them were significantly (p < 0.05) different between peiminine
treated and -untreated cells in which 45 metabolites were increased and the other
12 metabolites were decreased. Several of the affected metabolites, including
glucose, glutamine, oleate (18:1n9), and lignocerate (24:0), may be involved in
regulation of the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin
(mTOR) pathway and in the oxidative stress response upon peiminine exposure.
Peiminine predominantly modulated the pathways responsible for metabolism of
amino acids, carbohydrates, and lipids. Collectively, these results provide new
insights into the mechanisms by which peiminine modulates metabolic pathways to
inhibit colorectal cancer cell growth, supporting further exploration of
peiminine as a potential new strategy for treating colorectal cancer.
PMID- 28496004
TI - The lymph node ratio as an independent prognostic factor for node-positive triple
negative breast cancer.
AB - BACKGROUND: We aimed to evaluate the prognostic value of the lymph node ratio
(LNR) in patients with axillary lymph node-positive triple-negative breast cancer
(TNBC). METHODS: The prognostic efficacy was investigated in the first cohort
from the Surveillance, Epidemiology, and End Results (SEER) dataset (n=4114) and
was further validated in an independent cohort from Fudan University Shanghai
Cancer Center (n=417). Patients were classified into low-, medium- and high-risk
LNR groups. RESULTS: Multivariate analysis revealed that the LNR was an
independent predictor of overall survival (hazard ratio (HR) for high-risk LNR:
3.24; 95% confidence interval (CI): 2.56 to 4.09) and breast cancer-specific
survival (HR for high-risk LNR: 3.57; 95% CI: 2.76 to 4.62) in the SEER
population and also for disease-free survival (HR for high-risk LNR: 4.29; 95%
CI: 2.24-8.21) in the validation population. Subgroup analysis revealed that
patient classification according to the LNR could discriminate among groups of
patients with different survival rates based on pathological nodal (pN) staging.
CONCLUSION: The LNR shows potential for use as an additional prognostic factor
for TNBC patients with positive lymph node involvement. Considering the
heterogeneity of TNBC, use of the LNR might allow for optimization of the pN
staging system and should be considered when making treatment decisions.
PMID- 28496005
TI - Circulating plasma microRNAs as potential markers to identify EGFR mutation
status and to monitor epidermal growth factor receptor-tyrosine kinase inhibitor
treatment in patients with advanced non-small cell lung cancer.
AB - We aimed to identify a panel of circulating plasma microRNAs that can predict
EGFR mutation status and monitor epidermal growth factor receptor-tyrosine kinase
inhibitor treatment in patients with non-small cell lung cancer. Microarrays were
performed for the preliminary screening of dysregulated microRNAs in 9 EGFR
mutation-positive patients versus healthy controls. MiR-107 was upregulated and
miR-195 was downregulated in the exon 19 deletion versus wild-type group. The
areas under the receiver operating characteristic curves for miR-107, miR-195,
and a panel of these 2 microRNAs were 0.72, 0.75, and 0.74, with sensitivities
and specificities of 64.7% and 76.6%, 71.8% and 69.1%, and 71.7% and 78.9%,
respectively. MiR-122 was significantly upregulated in the p.L858R versus wild
type group. An area under the receiver operative characteristic curve of 0.75
suggests that miR-122 might be a specific biomarker for patients with the p.L858R
mutation. In addition, dynamic changes in these 3 microRNAs were also found to
correlate with responses to epidermal growth factor receptor-tyrosine kinase
inhibitor treatment, indicating that circulating plasma microRNAs may represent
potential biomarkers for monitoring epidermal growth factor receptor-tyrosine
kinase inhibitor treatment. This study demonstrates the prospective application
of circulating plasma microRNAs as potential non-invasive, convenient biomarkers
for patients with EGFR-sensitive mutations.
PMID- 28496006
TI - Gene expression signature of Gleason score is associated with prostate cancer
outcomes in a radical prostatectomy cohort.
AB - Prostate cancer (PCa) is a leading cause of cancer-related mortality worldwide.
Gleason score (GS) is one of the best predictors of PCa aggressiveness, but
additional tumor biomarkers may improve its prognostic accuracy. We developed a
gene expression signature of GS to enhance the prediction of PCa outcomes.
Elastic net was used to construct a gene expression signature by contrasting GS 8
10 vs. <=6 tumors in The Cancer Genome Atlas (TCGA) dataset. The constructed
signature was then evaluated for its ability to predict recurrence and metastatic
lethal (ML) progression in a Fred Hutchinson (FH) patient cohort (N=408;
NRecurrence=109; NMLprogression=27). The expression signature included
transcripts representing 49 genes. In the FH cohort, a 25% increase in the
signature was associated with a hazard ratio (HR) of 1.51 (P=2.7*10-5) for
recurrence. The signature's area under the curve (AUC) for predicting recurrence
and ML progression was 0.68 and 0.76, respectively. Compared to a model with age
at diagnosis, pathological stage and GS, the gene expression signature improved
the AUC for recurrence (3%) and ML progression (6%). Higher levels of the
signature were associated with increased expression of genes in cell cycle
related pathways and decreased expression of genes in androgen response, estrogen
response, oxidative phosphorylation, and apoptosis. This gene expression
signature based on GS may improve the prediction of recurrence as well as ML
progression in PCa patients after radical prostatectomy.
PMID- 28496007
TI - Association between tea consumption and risk of cognitive disorders: A dose
response meta-analysis of observational studies.
AB - BACKGROUND: The epidemiological evidence for a dose-response relationship between
tea consumption and risk of cognitive disorders is sparse. The aim of the study
was to summarize the evidence for the association of tea consumption with risk of
cognitive disorders and assess the dose-response relationship. METHODS: We
searched electronic databases of Pubmed, Embase, and Cochrane Library (from 1965
to Jan 19, 2017) for eligible studies that published in the international
journals. A random-effects model was used to pool the most adjusted odds ratios
(ORs) and the corresponding 95% confidence intervals (CIs). RESULTS: Seventeen
studies involving 48,435 participants were included in our study. The meta
analysis showed that a higher tea consumption was associated with a significant
reduction in the risk of cognitive disorders (OR=0.73, 95% CI: 0.65-0.82). When
considering the specific types of tea consumption, the significantly inverse
association is only found in green tea consumption (OR=0.64, 95% CI: 0.53-0.77)
but not in black/oolong tea consumption (OR=0.75, 95% CI: 0.55-1.01). Dose
response meta-analysis indicated that tea consumption is linearly associated with
a reduced risk of cognitive disorders. An increment of 100 ml/day, 300 ml/day,
and 500 ml/day of tea consumption was associated with a 6% (OR=0.94, 95% CI: 0.92
0.96), 19% (OR=0.81, 95% CI: 0.74-0.88), and 29% (OR=0.71, 95% CI: 0.62-0.82)
lower risk of cognitive disorders. CONCLUSIONS: Tea consumption is inversely and
linearly related to the risk of cognitive disorders. More studies are needed to
further confirm our findings.
PMID- 28496009
TI - Dynamic changes in clonal cytogenetic architecture during progression of chronic
lymphocytic leukemia in patients and patient-derived murine xenografts.
AB - Subclonal heterogeneity and clonal selection influences disease progression in
chronic lymphocytic leukemia (CLL). It is therefore important that therapeutic
decisions are made based on an understanding of the CLL clonal architecture and
its dynamics in individual patients. Identification of cytogenetic abnormalities
by FISH remains the cornerstone of contemporary clinical practice and provides a
simple means for prognostic stratification. Here, we demonstrate that multiplexed
FISH can enhance recognition of CLL subclonal repertoire and its dynamics during
disease progression, both in patients and CLL patient-derived xenografts (PDX).
We applied a combination of patient-specific FISH probes to 24 CLL cases before
treatment and at relapse, and determined putative ancestral relationships between
subpopulations with different cytogenetic features. We subsequently established 7
CLL PDX models in NOD/Shi-SCID/IL-2Rgammactm1sug/Jic (NOG) mice. Application of
multiplexed-FISH to these models demonstrated that all of the identified
cytogenetic subpopulations had leukemia propagating activity and that changes in
their representation during disease progression could be spontaneous, accelerated
by treatment or treatment-induced. We conclude that multiplexed-FISH in
combination with PDX models have the potential to distinguish between spontaneous
and treatment-induced clonal selection, and therefore provide a valuable tool for
the pre-clinical evaluation of novel therapies.
PMID- 28496010
TI - Characteristics of delayed intracerebral hemorrhage after ventriculoperitoneal
shunt insertion.
AB - BACKGROUND: Delayed intracerebral hemorrhage after ventriculoperitoneal (VP)
shunt insertion is rare and has not been well investigated previously. Its
characteristics is still unknown. OBJECTIVE: We reported 12 patients with delayed
intracerebral hemorrhage after VP shunt to investigate the potential risk factors
and the outcome. RESULTS: 12 patients (1.59%) of all the 754 hydrocephalus had
delayed intracerebral hemorrhage after VP shunt insertion. 4 patients were women
and 8 patients were men, ranging in age from 50 to 76 years. The delayed cerebral
hemorrhage from day 3 to day 7 post operation was diagnosed by repeated CT. The
delayed intracerebral hemorrhage was significantly related to age, prior
craniotomy operation history and manipulation of valve system (3-7 days). Neither
gender sexuality nor potential risk factors for postoperative hemorrhage
(including anticoagulation/antiplatelet status, liver disease, diabetes,
hypertension), time of shunt attempt affected the happen of delayed intracerebral
hemorrhage. MATERIALS AND METHODS: The clinical characteristics including sex,
age, anticoagulation/antiplatelet status, liver disease, diabetes, hypertension,
craniotomy operation history, manipulation of valve system and time of shunt
attempt of 754 patients who were surgically treated of VP shunt at the first
affiliated hospital of Soochow University between 2007 and 2013 were reviewed
retrospectively. The potential risk factors of the delayed intracerebral
hemorrhage were statistically analyzed. CONCLUSIONS: This study summarizes the
presentation and outcome of a series of 12 patients with delayed intracerebral
hemorrhage after VP shunt. Age >= 60 years, prior craniotomy operation and
manipulation of the valve system are statistically significant to the delayed
hematoma secondary to VP shunt.
PMID- 28496011
TI - Polymer toxicity in neurodegeneration FENIB.
PMID- 28496012
TI - Daytime behavior of Pteropus vampyrus in a natural habitat: the driver of viral
transmission.
AB - Flying foxes, the genus Pteropus, are considered viral reservoirs. Their colonial
nature and long flight capability enhance their ability to spread viruses
quickly. To understand how the viral transmission occurs between flying foxes and
other animals, we investigated daytime behavior of the large flying fox (Pteropus
vampyrus) in the Leuweung Sancang conservation area, Indonesia, by using
instantaneous scan sampling and all-occurrence focal sampling. The data were
obtained from 0700 to 1700 hr, during May 11-25, 2016. Almost half of the flying
foxes (46.9 +/- 10.6% of all recorded bats) were awake and showed various levels
of activity during daytime. The potential behaviors driving disease transmission,
such as self-grooming, mating/courtship and aggression, peaked in the early
morning. Males were more active and spent more time on sexual activities than
females. There was no significant difference in time spent for negative social
behaviors between sexes. Positive social behaviors, especially maternal cares,
were performed only by females. Sexual activities and negative/positive social
behaviors enable fluid exchange between bats and thus facilitate intraspecies
transmission. Conflicts for living space between the flying foxes and the ebony
leaf monkey (Trachypithecus auratus) were observed, and this caused daily
roosting shifts of flying foxes. The ecological interactions between bats and
other wildlife increase the risk of interspecies infection. This study provides
the details of the flying fox's behavior and its interaction with other wildlife
in South-East Asia that may help explain how pathogen spillover occurs in the
wild.
PMID- 28496013
TI - Enhancement of bactericidal effects of sodium hypochlorite in chiller water with
food additive grade calcium hydroxide.
AB - An alkaline agent, namely food additive grade calcium hydroxide (FdCa(OH)2) in
solution at 0.17%, was evaluated for its bactericidal efficacies in chiller water
with sodium hypochlorite (NaOCl) at a concentration of 200 ppm total residual
chlorine. Without organic material presence, NaOCl could inactivate Salmonella
Infantis and Escherichia coli within 5 sec, but in the presence of fetal bovine
serum (FBS) at 0.5%, the bactericidal effects of NaOCl were diminished
completely. FdCa(OH)2 solution required 3 min to inactivate bacteria with or
without 5% FBS. When NaOCl and FdCa(OH)2 were mixed at the final concentration of
200 ppm and 0.17%, respectively, the mixed solution could inactivate bacteria at
acceptable level (103 reduction of bacterial titer) within 30 sec in the presence
of 0.5% FBS. The mixed solution also inhibited cross-contamination with S.
Infantis or E. coli on chicken meats. It was confirmed and elucidated that
FdCa(OH)2 has a synergistic effect together with NaOCl for inactivating
microorganisms.
PMID- 28496014
TI - Prognostic Factors for In-Hospital and Long-Term Survival in Patients with Acute
ST-Segment Elevation Myocardial Infarction after Percutaneous Coronary
Intervention.
AB - Acute ST segment elevation myocardial infarction (STEMI) is one of the causes of
death and disability in patients with cardiovascular diseases. This study aimed
to investigate the prognostic factors of in-hospital and long-term survival in
patients with acute STEMI undergoing percutaneous coronary intervention (PCI).
Patients with STEMI undergoing PCI were divided into the death group (n = 54) and
the survival group (n = 306) based on the outcomes during hospitalization. The
routine blood and biochemistry tests, Killip classes and global registry of acute
coronary events (GRACE) risk score were detected. The 1-, 2- and 3-year survival
rates after PCI was observed through a 3-year follow-up. The survival factors,
survival rates and multivariate analyses were conducted using Logistic regression
analysis, Kaplan-Meier survival analysis and Cox proportional hazards regression.
The incidence of cardiogenic shock and anterior wall MI (AWMI), the serum levels
of gamma-glutamyl endopeptidase (gamma-GGT) and creatine kinase isoenzyme MB (CK
MB), Killip classes and GRACE risk score were higher in the death group, compared
with the survival group. AWMI, cardiogenic shock, high serum levels of gamma-GGT
and CK-MB, Killip class III-IV and high GRACE risk scores were associated with in
hospital mortality. AWMI, cardiogenic shock, Killip class III-IV and high GRACE
risk scores were correlated with a poor long-term survival. Our findings have
demonstrated that AWMI, cardiogenic shock, high serum levels of gamma-GGT and CK
MB, Killip class III-IV, and high GRACE risk scores are risk factors for in
hospital and long-term prognosis of acute STEMI patients.
PMID- 28496015
TI - Determining the Possible Etiology of Hospital-Acquired Pneumonia Using a Clone
Library Analysis in Japan.
AB - Obtaining precise etiological information regarding causative bacteria is
important for the proper use of antimicrobials in hospital-acquired pneumonia
(HAP), which is associated with a high rate of mortality. The aim of this study
was to comparatively investigate the bacterial diversity in bronchoalveolar
lavage fluid (BALF) in Japanese patients with HAP by the clone library method
using the 16S rRNA gene. This study included Japanese patients with HAP who were
treated at our hospital and referring hospitals. BALF specimens were obtained
from pneumonia lesions identified on chest radiographs and/or computed
tomography. Sputum specimens were also evaluated in patients with sputum
production. Sixty-eight patients were ultimately enrolled. BALF cultivation
revealed bacterial positivity in 53 of 68 (77.9%) patients, and Staphylococcus
aureus (30.9%) was the most frequently isolated, followed by Pseudomonas
aeruginosa (16.2%), and Escherichia coli (10.3%). In contrast, the clone library
analysis identified the presence of some bacterial phenotype in 65 of 68 (95.6%)
patients, and streptococci (16.2%), Corynebacterium species (11.8%), anaerobes
(10.3%) were frequently detected as the predominant phylotypes. Both methods
tended to detect S. aureus, Klebsiella pneumoniae, and E. coli in patients with
late-onset pneumonia. In addition, the cases that phylotypes of S. aureus and P.
aeruginosa were found to account for > 5% of the bacterial flora of each case
were 42.9% and 72.7%, respectively. These results indicate that attention should
be paid to the roles of gram-positive bacilli such as streptococci,
Corynebacterium species and anaerobes, in addition to Gram-negative bacilli, in
the pathogenesis of HAP.
PMID- 28496016
TI - Effects of a Rebamipide Mouthwash on Stomatitis Caused by Cancer Chemotherapy
Evaluation of the Efficacy by Patients Themselves.
AB - Anticancer drug-induced stomatitis develops in 30% to 40% of cancer cases that
undergo chemotherapy. However, medications for this condition are not
commercially available in Japan. Upon obtaining approval of the ethics committee,
a mouthwash containing rebamipide as the active ingredient (rebamipide mouthwash)
was administered to one inpatient and four outpatients, who had developed
stomatitis caused by cancer chemotherapy. Starting from 14 d after the
administration of the rebamipide mouthwash, the patients scored a stomatitis
survey on oral state, pain level, and diet and recorded the number of times they
gargled, as well as any stomatitis observations, in a stomatitis diary. The total
scores for the points for each of the three types of survey sections were
classified into Grades 0 to 4 and evaluated as a stomatitis evaluation score
(SES). The SES became "0" in three out of the five patients within 14 d of
treatment. No change in SES was found in one patient. In the remaining patients,
SES became "0" once but increased again later. Using image analysis software
(ImageJ), the area at which the stomatitis was observed was measured. When
comparing SES and change in the area in patients who agreed to participate,
gradual reductions in the extent of stomatitis was observed even during the
period when SES did not change. Having patients fill in an observation chart was
effective for grasping changes in symptoms in outpatients.
PMID- 28496017
TI - Comparison of the Incidence of Complications and Secondary Surgical Interventions
Necessary in Patients with Chronic Lower Limb Ischemia Treated by Both Open and
Endovascular Surgeries.
AB - BACKGROUND: Peripheral arterial disease (PAD) affects 3%-10% of the population
before the age of 70 years and 15%-20% after that age.The aim of the study was to
compare the incidence of complications and secondary interventions in patients
who underwent each type of treatment. METHODS: We analyzed 734 medical records of
the Department of Surgery at the 4th Military Teaching Hospital in Wroclaw, In
total, 394 were operated on with open surgery; an endarterectomy (59.39%), a
vascular prosthesis implantation (31.01%), or both of these techniques (6.6%),
and 340 patients had angioplasty with (50.59%) or without stenting (49.41%).
RESULTS: There were no statistically significant differences in the incidence of
corresponding complications. The exception was the infection of the wound;
significantly fewer were reported in the case of endovascular procedures (p =
0.0087). There were 12 occasions (3.53%) during endovascular surgeries when
intraoperative conversion or re-operation using the open method occurred. In the
case of open surgery, the mean hospital stay was 7.77 days (median: 8, mode: 8),
while for endovascular management it was equal to 4.68 days (median: 4, mode: 3),
p <0.0001. CONCLUSION: The endovascular method results in a similar re-operation
rate and number of complications as open surgery.
PMID- 28496018
TI - Effects of heat stress on bovine preimplantation embryos produced in vitro.
AB - Summer heat stress decreases the pregnancy rate in cattle and has been thought to
be associated with the early embryonic death caused by the elevation of maternal
body temperature. In vitro cultures have been widely used for the evaluation of
effects of heat stress on oocytes, fertilization, preimplantation, and embryonic
development. Susceptibility to heat stress is present in developmental stages
from oocytes to cleavage-stage (before embryonic gene activation, EGA) embryos,
leading to a consequent decrease in developmental competence. On the other hand,
advanced-stage embryos such as morula or blastocysts have acquired
thermotolerance. The mechanism for the developmental stage-dependent change in
thermotolerance is considered to be the accumulation of antioxidants in embryos
in response to heat-inducible production of reactive oxygen species. The
supplementation of antioxidants to the culture media has been known to neutralize
the detrimental effects of heat stress. Besides, EGA could be involved in
acquisition of thermotolerance in later stages of embryos. Morulae or blastocysts
can repair heat-induced unfolded proteins or prevent DNA damage occurring in
processes such as apoptosis. Therefore, embryo transfer (ET) that can bypass the
heat-sensitive stage could be a good solution to improve the pregnancy rate under
heat stress. However, frozen-thawed ET could not improve the pregnancy rate as
expected. Frozen-thawed blastocysts were more sensitive to heat stress and showed
less proliferation upon heat exposure, compared to fresh blastocysts. Therefore,
further research is required to improve the reduction in pregnancy rates due to
summer heat stress.
PMID- 28496019
TI - Age-associated changes in granulosa cells and follicular fluid in cows.
AB - Age-associated decline in oocyte quality is common in mammals. Oocytes take a
long time to reach their full-grown size in large animals, and maternal physical
conditions profoundly affect follicle development. Aging affects the oocyte
itself as well as the surrounding environment, such as granulosa cells and
follicular fluid. This review discusses age-associated changes that occur in
granulosa cells and follicular fluid in cows and suggests that age-associated
decline in granulosa cells and follicular fluid hampers proper oocyte
development.
PMID- 28496020
TI - Predictors of Long-Term Mortality in Patients With Acute Heart Failure.
AB - To investigate parameters which were related with long-term mortality in patients
hospitalized for acute heart failure (AHF).A total of 287 patients with AHF
presenting to the First Affiliated Hospital of Nanjing Medical University were
enrolled into the registry from April 2012 to January 2015. The primary endpoint
was all-cause mortality within 1 year; the association between variables and
prognosis was assessed after 1 year.Among the 287 patients, 17 did not continue
follow-up and 47 (17.4%) passed away. Baseline NT-proBNP and sST2 concentrations
were higher amongst deceased than among survivors (P < 0.001). Serum sodium
concentrations of patients who died were lower (P < 0.001). In receiver operator
characteristics (ROC) analyses, the area under the curve (AUC) values for NT
proBNP, sST2, and serum sodium to predict 1-year mortality were 0.699 (95%CI
0.639-0.755), 0.692, (95%CI 0.634-0.747), and 0.694 (95%CI 0.634-0.750),
respectively. The optimal cut-off points for NT-proBNP, sST2, and serum sodium
were 2137.0 ng/L, 35.711 ng/mL, and 136.6 mmol/L, respectively. In Cox regression
analysis, ln-transformed NT-proBNP (HR 1.546, P = 0.039), ln-transformed sST2
(HR1.542, P = 0.049), and serum sodium (HR 0.880, P = 0.000) values reliably
predicted long-term mortality after multivariable adjustment.In patients with
acute heart failure, NT-proBNP, sST2 and serum sodium are potential predictors of
1-year mortality.
PMID- 28496021
TI - Feasibility and Safety of Transulnar Catheterization in Ipsilateral Radial Artery
Occlusion.
AB - To investigate the postprocedural cardiovascular events and vascular outcomes,
including hand ischemia and neurological compromise, after transulnar (TU)
catheterization in ipsilateral radial artery occlusion.Previous randomized trials
have shown that the transulnar (TU) approach for coronary angiogram and
intervention has safety and outcomes similar to those of the transradial (TR)
approach. However, the safety of the TU procedure when ipsilateral radial artery
occlusion occurs is unknown.We retrospectively reviewed 87 TU cases with
ipsilateral radial artery occlusion confirmed by a forearm angiogram. Eighty
percent of these patients had a history of ipsilateral radial artery cannulation
or surgery. We avoided the use of over-sized sheaths or applied a sheathless
approach during surgery.No ulnar artery occlusion was observed by subsequent
Doppler ultrasound or pulse oximetry. No patient developed hand ischemia or
serious complications requiring surgery or blood transfusion during the follow-up
period of 32.2 +/- 24.0 months. Review of the preprocedural forearm angiograms
showed that 95.7% of the patients possessed significant collaterals supplying
flow from the interosseous artery to the occluded radial artery remnant. Thus,
the blood circulation to the palmar arch and digital vessels was maintained even
when the ulnar artery was temporarily occluded by an in-dwelling ulnar arterial
sheath.TU catheterization was safe in patients with coexisting ipsilateral radial
artery occlusions and feasible for use in complex intervention procedures.
Cautious manipulation of ulnar artery cannulation and hemostasis helped decrease
the risk of hand ischemia.
PMID- 28496022
TI - Comparison of Efficacy and Safety of Azilsartan and Olmesartan in Patients With
Essential Hypertension.
AB - Many patients still have high blood pressure (BP) after treatment with
angiotensin II type 1 (AT1) receptor blockers (ARBs). We compared the efficacy
and safety of azilsartan to those of olmesartan in a prospective randomized
clinical trial. Sixty-four hypertensive patients who were treated with ARBs other
than azilsartan and olmesartan were enrolled in this study. We randomly assigned
patients to changeover from their prior ARBs to either azilsartan or olmesartan,
and followed the patients for 3 months. Systolic BP (SBP) in the azilsartan group
was significantly decreased at 3 months, and diastolic BP (DBP) and pulse rate
(PR) in the olmesartan group showed significant reductions after 3 months. There
were no significant differences in DeltaSBP, DeltaDBP, or DeltaPR (Delta = the
value at 3 months minus the value at 0 months) between the groups. Serum levels
of creatinine (Cr), uric acid (UA), and potassium (K) in the azilsartan group
significantly increased after 3 months. While the changes in Cr, UA, and K were
within the respective normal ranges, DeltaSBP was positively associated with
DeltaCr in the azilsartan group. In conclusion, there was no difference in the
depressor effects of azilsartan and olmesartan, and there were no serious changes
in biochemical parameters with azilsartan and olmesartan.
PMID- 28496023
TI - Bilateral Coronary-Pulmonary Artery Fistulas in Pulmonary Atresia With
Ventricular Septal Defect.
AB - We present a very rare case of bilateral coronary to pulmonary artery fistulas
associated with pulmonary atresia with ventricular septal defect. The courses of
coronary to pulmonary artery fistulas have to be clearly delineated by detailed
angiography prior to corrective surgery.
PMID- 28496024
TI - A Survival Case of Fulminant Right-Side Dominant Eosinophilic Myocarditis.
AB - A 59-year-old Japanese woman was admitted to a nearby hospital with dyspnea and
general malaise. Transthoracic echocardiography revealed right ventricular (RV)
dilatation with severely reduced systolic function and leftward shift of the
intraventricular septum. She was initially diagnosed with acute right heart
failure, and fell into cardiogenic shock requiring an intra-aortic balloon pump
and inotropic agents. An endomyocardial biopsy (EMB) demonstrated extensive
interstitial edema, infiltration of inflammatory cells including numerous
eosinophils, and myocytolysis with eosinophil degranulation. She was
histologically diagnosed with eosinophilic myocarditis. Steroid pulse therapy was
initiated, and her hemodynamic status improved along with dramatic recovery of
the RV function. EMB 6 days after the initiation of steroid pulse therapy showed
the disappearance of infiltration and degranulation of eosinophils, although
lymphocytic infiltration still remained. Positron emission tomography-computed
tomography (PET/CT) 23 days after steroid pulse therapy showed an increased 18F
FDG uptake in the intraventricular septum and left ventricle, suggesting
persistent myocardial inflammation. She was then treated with a maintenance dose
of prednisolone. She became free of symptoms and follow-up echocardiography
showed normal cardiac function 3 months after the initiation of corticosteroid
treatment. In addition, EMB and PET/CT showed no inflammation. This is the first
case report of fulminant and right-sided dominant eosinophilic myocarditis
successfully treated with corticosteroid.
PMID- 28496025
TI - Identification of a Novel GLA Gene Mutation, p.Ile239Met, in Fabry Disease With a
Predominant Cardiac Phenotype.
AB - Fabry disease (FD) is an X-linked inherited lysosomal storage disorder caused by
mutations in the GLA gene, encoding for the enzyme alpha-galactosidase A.
Although hundreds of mutations in the GLA gene have been described, many of them
are variants of unknown significance. Here we report a novel GLA mutation,
p.Ile239Met, identified in a large Hungarian three-generation family with FD. A
69 year-old female index patient with a clinical history of renal failure,
hypertrophic cardiomyopathy, and 2nd degree AV block was screened for mutation in
the GLA gene. Genetic screening identified a previously unreported heterozygous
mutation in exon 5 of the GLA gene (c.717A>G; p.Ile239Met). Family screening
indicated that altogether 6 family members carried the mutation (5 females, 1
male, average age: 55 +/- 16 years). Three family members, including the index
patient, manifested the cardiac phenotype of hypertrophic cardiomyopathy, while
two other family members were diagnosed with left ventricular hypertrophy. Taking
affection status as the presence of hypertrophic cardiomyopathy, left ventricular
hypertrophy or elevated lyso-Gb3 levels, all affected family members carried the
mutation. Linkage analysis of the family gave a two-point LOD score of 2.01
between the affection status and the p.Ile239Met GLA mutation. Lyso-Gb3 levels
were elevated in all carrier family members (range: 2.4-13.8 ng/mL; upper limit
of normal +2STD: <= 1.8 ng/mL). The GLA enzyme level was markedly reduced in the
affected male family member (< 0.2 umol/L/hour; upper limit of normal +/- 2STD:
>= 2.6 umol/L/hour). We conclude that the p. Ile239Met GLA mutation is a
pathogenic mutation for FD associated with predominant cardiac phenotype.
PMID- 28496026
TI - Computed tomography angiography reveals stenosis and aneurysmal dilation of an
aberrant right subclavian artery causing systemic blood pressure misreading in an
old Pekinese dog.
AB - A 14-year-old dog weighing 4 kg presented with hypotension only in the right
forelimb. Thoracic radiography revealed a round soft tissue opacity near the
aortic arch and below the second thoracic vertebra on a lateral view. Three
dimensional computed tomography angiography clearly revealed stenosis and
aneurysmal dilation of an aberrant right subclavian artery. Stenosis and aneurysm
of an aberrant subclavian artery should be included as a differential diagnosis
in dogs showing a round soft tissue opacity near the aortic arch and below the
thoracic vertebra on the lateral thoracic radiograph.
PMID- 28496027
TI - Expression profile of matricellular proteins in hypertrophied right ventricle of
monocrotaline-induced pulmonary hypertensive rats.
AB - Matricellular proteins, a non-structural extracellular matrix (ECM) component,
bind to and modulate various molecules including growth factor, cytokine,
protease, other ECM components and cell membrane receptors. While most
matricellular proteins are hardly expressed in normal adult tissue, they are re
expressed in heart tissue during cardiac diseases. The present study aimed to
clarify the mRNA expression profile of matricellular proteins [secreted protein
acidic and rich in cysteine: SPARC, hevin, thrombospondin (TSP)-1, -2 and -4,
CCN1 and 5, tenascin (Tn) C and N, periostin and osteopontin (OPN)] in
hypertrophied right ventricle (RV) of monocrotaline (MCT)-induced pulmonary
hypertensive rats. Male Wistar rats were intraperitoneally treated with MCT or
saline. Two or three weeks after MCT treatment, echocardiography was performed,
and mRNA expression of matricellular proteins was measured by real-time
polymerase chain reaction. MCT (2 weeks) induced pulmonary hypertension, RV
dysfunction and hypertrophy, which were all worsened 3 weeks after MCT treatment.
Expression of mRNA for SPARC, hevin, TnC, TSP-1, -2 and -4, CCN1 and 5, periostin
and OPN but not TnN was significantly upregulated in RV of MCT (2 weeks)-treated
rats. Expression of mRNA for TSP-4, CCN1 and 5 and periostin was continuously
increased in RV of MCT (3 weeks)-treated rats. The present study for the first
time revealed the mRNA expression profile for matricellular proteins in RV of MCT
treated rats for 2 or 3 weeks, which will be helpful to clarify the relationship
for matricellular proteins and pathogenesis of MCT-induced RV hypertrophy.
PMID- 28496028
TI - 10-year trends of educational differences in long sickness absence due to mental
disorders.
AB - OBJECTIVES: Mental disorders are a key cause of sickness absence (SA) and
challenge prolonging working careers. Thus, evidence on the development of SA
trends is needed. In this study, educational differences in long SAs due to
mental disorders were examined in two age groups among employees of the City of
Helsinki from 2004 to 2013. METHODS: All permanently and temporarily employed
staff aged 18-34 and 35-49 were included in the analyses (n=~27800 per year). SA
spells of >=14 days due to mental disorders were examined annually. Education was
classified to higher and lower levels. Joinpoint regression was used to identify
major turning points in SA trends. RESULTS: Joinpoint regression models showed
that lower educated groups had more long SAs spells due to mental disorders than
those groups with higher education. SA trends decreased during the study period
in all studied age and educational groups. Lower educated age groups had similar
SA trends. Younger employees with higher education had the fewest SAs.
CONCLUSIONS: A clear educational gradient was found in long SAs due to mental
disorders during the study period. SA trends decreased from 2004 to 2013.
PMID- 28496029
TI - A Newly Established Severity Scoring System in Predicting the Prognosis of
Patients with Severe Fever with Thrombocytopenia Syndrome.
AB - Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious
disease caused by novel Bunyavirus. Due to the peculiarity of SFTS, accurate
assessment is difficult to achieve with the current score systems. This study
aimed to establish a new severity scoring system in predicting the prognosis of
patients with SFTS. We included 123 patients with SFTS: 92 patients (45 males and
47 females), aged 59 +/- 12 years, in survive group and 31 patients (17 males and
14 females), aged 61 +/- 10 years, in death group. The lactate dehydrogenase
(LDH), the activated partial thromboplastin time (APTT), the saturation of pulse
oximeter oxygen (SpO2) and Glasgow Coma Scale (GCS) were measured. SFTS severity
scoring system was set up based on the above four factors and compared with the
Rapid Emergency Medicine Scores (REMS) and Acute Physiology and Chronic Health
Evaluation (APACHE II) Scores. Four parameters in the death group were all
significantly higher than survival group. The areas under the curves (AUC) of
REMS, APACHE II scores and SFTS severity scores were 0.734, 0.746 and 0.780
respectively. The Youden index of the SFTS severity score was the highest among
all the three scores (P < 0.01). If 15 was used as the cutoff value, the
sensitivity and specificity of SFTS severity score in predicting the death risk
for the patients were 74.2% and 76.1% respectively. The newly established SFTS
severity scoring system is more efficient to predict the prognosis of patients
with SFTS, compared with REMS and APACHE II.
PMID- 28496030
TI - Underuse of Cardiac Rehabilitation in Workers With Coronary Artery Disease -
Claims Database Survey in Japan.
AB - BACKGROUND: Workers with coronary artery disease (CAD) require evidence-based
care in order to return to work safely. We assessed the use of cardiac
rehabilitation (CR) among workers with CAD, and identified the factors associated
with CR use.Methods and Results:A retrospective cohort study based on data from a
health insurance claims database was conducted. We identified workers aged >=18
years who underwent percutaneous coronary intervention (PCI) or coronary artery
bypass grafting (CABG) between 2006 and 2013, and reviewed the utilization of
inpatient or outpatient CR. Logistic regression was used to identify the factors
associated with CR use. A total of 1,699 patients were included. The frequency of
inpatient and outpatient CR use was 23.7% (n=402) and 4.2% (n=72), respectively.
Patients diagnosed with ST-elevated myocardial infarction were most likely to
receive inpatient CR, and patients undergoing CABG were more likely to receive
inpatient CR than those undergoing PCI. Moreover, inpatient CR use was associated
with longer hospitalization duration, catecholamine use, and no history of
chronic kidney disease. Furthermore, both unstable and stable angina were
negatively correlated with outpatient CR use. CONCLUSIONS: Most of the Japanese
workers with CAD in this study did not undergo CR. The type of CAD was strongly
associated with inpatient and outpatient CR use. Thus, a strong evidence-practice
gap exists in secondary preventative care within this group of patients.
PMID- 28496031
TI - Atrial Septostomy for Left Atrial Decompression During Extracorporeal Membrane
Oxygenation by Inoue Balloon Catheter.
AB - BACKGROUND: Refractory pulmonary edema is an infrequent but serious complication
in patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO)
for myocardial failure. Left atrial (LA) decompression in this setting is
important. Although a few methods have been reported, the experience is mostly
limited to children. We aimed to evaluate the feasibility of Inoue balloon
catheter in percutaneous trans-septal LA decompression in adult cardiogenic
patients.Methods and Results:We retrospectively analyzed 16 procedures of trans
septal LA decompression by Inoue balloon catheter in 15 VA-ECMO patients (aged 22
65 years, 6 men) with refractory pulmonary edema from May 2012 to December 2014.
Mean left ventricular ejection fraction was 15%. The cause of cardiogenic shock
included 7 cases of ischemic heart disease, 1 of dilated cardiomyopathy, 5 of
myocarditis, and 2 of fatal ventricular arrhythmia.The procedures were performed
4.3 days after ECMO. Inoue balloon size was 24-27 mm. LA septostomy were
successfully created in 14 patients. Procedure time on average was 36.8 min
(range, 15-85 min). There were no procedure-related complications.Radiography on
the next day showed rapid resolution of pulmonary edema. CONCLUSIONS: Trans
septal LA decompression by Inoue balloon catheter is a feasible alternative
method for adult patients with refractory pulmonary edema under ECMO.
PMID- 28496032
TI - Farnesoid X receptor regulates the growth of renal adenocarcinoma cells without
affecting that of a normal renal cell-derived cell line.
AB - The farnesoid X receptor (FXR) is a bile acid-activated nuclear receptor which is
abundant in the liver, intestine, and kidney. FXR is a pivotal factor in
cholesterol/bile acid homeostasis but is involved in the growth of hepatocellular
carcinoma cells. In the present study, we investigated whether FXR is also
involved in the growth of renal adenocarcinoma cells. The cell growth of renal
adenocarcinoma cell line ACHN was inhibited by FXR knockdown and stimulated by
FXR ligand, while that of a normal renal cell-derived cell line, HK-2, was not
affected. The carcinoma-specific stimulation of cell growth by FXR was found to
arise from down-regulation of p53 and p21/Cip1 mRNA expression. Our study showed
that FXR stimulates proliferation of renal adenocarcinoma cells and that FXR
knockdown is useful for growth suppression of renal adenocarcinoma without
cytotoxicity to normal renal cells.
PMID- 28496033
TI - Joint toxicity of fluoroquinolone and tetracycline antibiotics to zebrafish
(Danio rerio) based on biochemical biomarkers and histopathological observation.
AB - Herein, we report on the joint toxicity of four fluoroquinolones and two
tetracyclines (beta-diketone antibiotics-DKAs) to zebrafish based on a series of
toxicological endpoints and histopathological observations. A positive dose
dependence was observed in DKA-exposure groups with a 72-hpf EC50 of 130.3 mg/L
for hatching rate, 120-hpf LC50 of 149.8 mg/L, and 120-hpf EC50 of 135.1 mg/L for
malformation rate. When zebrafish at 60 dpf were exposed to a series of DKA
concentrations (45, 60 and 90 mg/L) for 7, 14 and 21 days, creatine kinase and
AChE activities were significantly induced, and intracellular malondialdehyde
increased in all treatments except for the 45 mg/L treatment. The transcription
levels of AHRRa from livers were significantly (p < 0.05) up-regulated in all
treatments after two months of DKA exposure. CKma expression from skeletal muscle
was significantly down-regulated in the 90 mg/L treatment. A remarkable down
regulation of CYP3A65 was observed in the 60 mg/L treatment. DKA exposure
resulted in severe tissue damage including mitochondria swelling, reduction of
mitochondrial cristae, deepening of mitochondrial cristae bands, and decreasing
and even disappearance of the rough endoplasmic reticulum. Total sperm motility
was decreased by ca. 30% due to DKA exposure. These results provide important
information for toxicity and health risks due to mixed DKA exposure in aquatic
environments.
PMID- 28496034
TI - Effect of perinatal exposure to Bisphenol-A on DNA methylation and histone
acetylation in cerebral cortex and hippocampus of postnatal male mice.
AB - Bisphenol-A (BPA) is an estrogenic endocrine disruptor mostly used for the
production of polycarbonate plastics and epoxy resins. Recently we have reported
that perinatal BPA exposure impaired spatial memory through upregulation of
synaptic proteins Neurexin1 and Neuroligin3 in male mice. As epigenetic mechanism
is a key regulator of memory, we hypothesized that BPA might influence memory
through epigenetic regulation of gene expression. Here we provide evidence that
perinatal exposure to BPA decreased 5-mC DNA but increased histone H3 acetylation
in cerebral cortex and hippocampus of postnatal 3 and 8 weeks male mice. BPA
exposure also increased mRNA levels of DNMT1 and DNMT3a in cerebral cortex of 3
and 8 weeks; whereas in hippocampus DNMT1 mRNA increased in 3 weeks but decreased
in 8 weeks and DNMT3a showed no change. Further, HDAC2 mRNA and protein increased
in cerebral cortex of both ages and in hippocampus it increased in 3 weeks but
decreased in 8 weeks. Altogether, our results demonstrate that the perinatal BPA
exposure induces epigenetic changes that possibly underlie the enduring effect of
BPA on brain function and behavior.
PMID- 28496035
TI - Alleviating effects of artificial tear instillation on S-1-induced ocular
toxicity in dogs.
AB - S-1 is an anticancer agent that consists of tegafur, gimeracil, and oteracil
potassium at a molar ratio of 1:0.4:1. S-1 is used to treat metastatic and
resectable gastric cancer. However, the extensive use of S-1 in clinical practice
results in watery eyes, a serious clinical problem, which worsens patients'
quality of life. Although repeated instillation of artificial tears is
recommended, therapy or prophylaxis against S-1-induced ocular toxicity has not
been established. In the present study, we evaluated the alleviating effects of
repeated artificial tear instillation on S-1-induced ocular toxicity in dogs. Ten
beagle dogs (5 males and 5 females) were orally administered 3 mg/kg/day of S-1
for up to 21 days. Five drops of artificial tears were instilled to the left eye,
eight times daily, within 6 hr after S-1 administration. The mean cornea staining
score tended to be low in the left eye with repeated artificial tear
instillation. In 4 out of 10 dogs, the corneal staining score of the left eye was
more than 2-fold lower than that of the right eye. The incidence of dogs
indicating normal tear drainage increased and stenosed tear drainage decreased by
repeated artificial tear instillation. In conclusion, we demonstrated that
artificial tear instillation can alleviate corneal surface damage induced by S-1
in dogs.
PMID- 28496037
TI - Mono-butyl phthalate-induced mouse testis injury is associated with oxidative
stress and down-regulated expression of Sox9 and Dazl.
AB - Mono-butyl phthalate (MBP) has reproductive toxicity but the related mechanisms
have not been fully elucidated in vivo. We exposed male Balb/c mice to MBP by
gavage at doses of 0, 25, 50, 100, 200 mg/kg for 14 days, and then evaluated the
testicular alterations at the histological and molecular levels. MBP reduced
mouse sperm count along with sperm malformation and seminiferous tubule
degeneration in a dose-dependent manner. MBP dosed at 200 mg/kg significantly
increased reactive oxygen species and malondialdehyde content in mouse testes.
High doses of MBP (200 mg/kg) also significantly reduced mRNA expressions of
testis growth and function related genes (Sox9 and Dazl). Our findings suggest
that oxidative stress and down-regulated expression of Sox9 and Dazl may play
important roles in MBP-induced testis injury.
PMID- 28496036
TI - Tissue toxicokinetics of perfluoro compounds with single and chronic low doses in
male rats.
AB - To examine the kinetics of low doses of perfluoro compounds (PFCs), we
administered perfluorohexanoic acid (C6A), perfluorooctanoic acid (C8A),
perfluorononanoic acid (C9A) and perfluorooctane sulfonate (C8S) with a single
oral dose (50-100 MUg/kg BW), and in drinking water at 1, 5, and 25 MUg/L for one
and three months to male rats; and examined the distribution in the brain, heart,
liver, spleen, kidney, whole blood and serum. C6A was very rapidly absorbed,
distributed and eliminated from the tissues with nearly the same tissue t1/2 of 2
3 hr. Considering serum Vd, and the tissue delivery, C6A was mainly in the serum
with the lowest delivery to the brain; and no tissue accumulation was observed in
the chronic studies as estimated from the single dose study. For the other PFCs,
the body seemed to be an assortment of independent one-compartments with a longer
elimination t1/2 for the liver than the serum. The concentration ratio of
liver/serum increased gradually from C0 to a steady state. The high binding
capacity of plasma protein may be the reason for the unusual kinetics, with only
a very small fraction of free PFCs moving gradually to the liver. Although the
tissue specific distribution was time dependent and different among the PFCs, the
Vd and ke of each tissue were constant throughout the study. The possibility of
extremely high C6A accumulation in the human brain and liver was suggested, by
comparing the steady state tissue concentration of this study with the human data
reported by Perez et al. (2013).
PMID- 28496038
TI - Methylmercury induces hyaluronan synthesis in cultured human brain microvascular
endothelial cells and pericytes via different mechanisms.
AB - In a cerebrum damaged by methylmercury, where neuropathological lesions tend to
localize along deep sulci and fissures, edematous changes in white matter have
been proposed as the cause of such localization. Since hyaluronan has a high
water-retention capability and can contribute to the progression of edematous
changes, we hypothesize that methylmercury increases hyaluronan in brain
microvascular cells. Our experimental results indicate that methylmercury induces
the expression of hyaluronan in cultured human microvascular endothelial cells
and pericytes through the induction of expressed UDP-glucose dehydrogenase and
hyaluronan synthase 2, respectively. After exposure to methylmercury, hyaluronan
largely accumulates in perivascular space, where it contributes to the
progression of edematous changes.
PMID- 28496039
TI - Pyrolysis of UR-144, a synthetic cannabinoid, augments an affinity to human CB1
receptor and cannabimimetic effects in mice.
AB - Drug abusers most often smoke 'herbal incense' as a cigarette or inhale it using
a smoking tool. Smoking may cause pyrolysis of the drug and produce decomposed
products of which biological effect has never been investigated. The synthetic
cannabinoid UR-144 is known to undergo thermal degradation, giving a ring-opened
isomer, so-called UR-144 degradant. The present study demonstrates by using UR
144 as a model drug that the smoke of burned UR-144 contains the UR-144
degradant. The UR-144 degradant showed approximately four fold higher agonist
activity to human CB1 receptor and augmented hypothermic and akinetic actions in
mice compared to UR-144. These results indicate that smoking behavior may
increase psychological actions of the certain synthetic cannabinoids.
PMID- 28496041
TI - A rapid mitochondrial toxicity assay utilizing rapidly changing cell energy
metabolism.
AB - Drug-induced liver injury is a major cause of safety-related drug-marketing
withdrawals. Several drugs have been reported to disrupt mitochondrial function,
resulting in hepatotoxicity. The development of a simple and effective in vitro
assay to identify the potential for mitochondrial toxicity is thus desired to
minimize the risk of causing hepatotoxicity and subsequent drug withdrawal. An in
vitro test method called the "glucose-galactose" assay is often used in drug
development but requires prior-culture of cells over several passages for
mitochondrial adaptation, thereby restricting use of the assay. Here, we report a
rapid version of this method with the same predictability as the original method.
We found that replacing the glucose in the medium with galactose resulted in
HepG2 cells immediately shifting their energy metabolism from glycolysis to
oxidative phosphorylation due to drastic energy starvation; in addition, the
intracellular concentration of ATP was reduced by mitotoxicants when glucose in
the medium was replaced with galactose. Using our proposed rapid method,
mitochondrial dysfunction in HepG2 cells can be evaluated by drug exposure for
one hour without a pre-culture step. This rapid assay for mitochondrial toxicity
may be more suitable for high-throughput screening than the original method at an
early stage of drug development.
PMID- 28496040
TI - Induction of human cytochrome P450 3A enzymes in cultured placental cells by
thalidomide and relevance to bioactivation and toxicity.
AB - Evidence has been presented for auto-induced human cytochrome P450 3A enzyme
involvement in the teratogenicity and clinical outcome of thalidomide due to
oxidation to 5-hydroxythalidomide and subsequent metabolic activation in livers.
In this study, more relevant human placenta preparations and placental BeWo cells
showed low but detectable P450 3A4/5 mRNA expression and drug oxidation
activities. Human placental microsomal fractions from three subjects showed
detectable midazolam 1'- and 4-hydroxylation and thalidomide 5-hydroxylation
activities. Human placental BeWo cells, cultured in the recommended media, also
indicated detectable midazolam 1'- and 4-hydroxylation and thalidomide 5
hydroxylation activities. To reduce any masking effects by endogenous hormones
used in the recommended media, induction of P450 3A4/5 mRNA and oxidation
activities were measured in placental BeWo cells cultured with a modified medium
containing 5% charcoal-stripped fetal bovine serum. Thalidomide significantly
induced P450 3A4/5, 2B6, and pregnane X receptor (PXR) mRNA levels 2 to 3-fold,
but rifampicin only enhanced P450 3A5 and PXR mRNA under the modified media
conditions. Under these modified conditions, thalidomide also significantly
induced midazolam 1'-hydroxylation and thalidomide 5-hydroxylaion activities 3
fold but not bupropion hydroxylation activity. Taken together, activation of
thalidomide to 5-hydroxythalidomide with autoinduction of P450 3A enzymes in
human placentas, as well as livers, is suggested in vivo.
PMID- 28496042
TI - High sensitivity of testicular function to titanium nanoparticles.
AB - Titanium dioxide nanoparticles (TiNPs) present toxicity in organs such as the
liver, lung, and intestine. The testis has also been reported as a target organ
of TiNPs. We recently reported that TiNPs had no genotoxic effect in the liver
and bone marrow, while showing clear testicular dysfunction. In this paper,
therefore, we systematically compared the sensitivity of hepatic function using
biochemical markers and testicular function against TiNPs. Male C57BL/6J mice
were injected intravenously with TiNPs (Aeroxide-P25, at doses of 0.1, 1, 2, and
10 mg/kg body weight) once per week for 4 consecutive weeks. Mice were sacrificed
three days after the last injection. Body weights, liver weights, and testicular
related organ weights were not found to be changed by TiNP treatment. Moreover,
TiNPs caused no hepatic damage, as evaluated by alanine aminotransferase and
aspartate aminotransferase indexes. The testicular function, however, was clearly
impaired by TiNP treatment; reduction in two sperm motion parameters (motile
percent and progressive percent) and sperm numbers in cauda epididymides was
seen. We observed Ti accumulation in the liver but not in the testis, as well as
no change in plasma levels of sex hormones related to spermatogenesis. Our
findings indicate that the testis is highly sensitive to TiNPs, as compared to
the liver. We believe that, when considering the biological effects of TiNPs,
testicular function (especially motility ability) may be a sensitive indicator.
PMID- 28496043
TI - Length effects of single-walled carbon nanotubes on pulmonary toxicity after
intratracheal instillation in rats.
AB - We aimed to evaluate the effects of the length of single-walled carbon nanotubes
(SWCNTs) on pulmonary toxicity in rats. Each rat received a single intratracheal
instillation of short (S-) (average length of 0.40 MUm) or long (L-) (average
length of 2.77 MUm) SWCNTs at a dose of 1 mg/kg and was observed for the next 6
months. Neither S- nor L-SWCNTs affected clinical signs, body weight, or autopsy
findings. An increase in lung weight was observed after instillation of S- or L
SWCNTs; however, lung weights were slightly higher in the rats that were
administered the S-SWCNTs. Distinct differences in bronchoalveolar lavage fluid
(BALF) composition were observed between the S- and L-SWCNT-treated rats as early
as 7 days after the intratracheal instillations of the SWCNTs. The S-SWCNTs
caused persistent lung injury and inflammation during the 6-month observational
period. However, the L-SWCNTs induced minimal lung injury and inflammation.
Although the S- and L-SWCNTs changed BALF parameters and histopathological
features of the lung, the magnitudes of the changes observed after the S-SWCNT
treatment were greater than the respective changes observed after the L-SWCNT
treatment. These findings indicate that the severity of the pulmonary toxicity
caused after intratracheal instillation of SWCNT depends on the length of the
SWCNTs. It appears that shorter SWCNTs induce greater pulmonary toxicity than
longer SWCNTs do.
PMID- 28496044
TI - Comparison of nephrotoxicity between two gadolinium-contrasts, gadodiamide and
gadopentetate in patients with mildly diminished renal failure.
AB - Although gadolinium (Gd)-based contrast media have been found to be nephrotoxic,
their nephrotoxicity, and the dependence of nephrotoxicity on chelate types, have
not been assessed in patients with normal or mildly diminished renal failure.
This prospective, randomized study compared the nephrotoxicity of low doses of
the nonionic Gd-based contrast medium gadodiamide (Omniscan(r)) and the ionic Gd
based contrast medium gadopentetate (Magnevist(r)) in patients with serum
creatinine < 1.6 mg/dL. Patients aged 20 to 80 years, weighing 45 to 70 kg and
with normal or < 1.6 mg/dL Serum-creatinine in the 3 months prior to undergoing
magnetic resonance imaging (MRI) of brain, were enrolled. Patients were
randomized to receive 0.1 mol/kg gadodiamide or gadopentetate. Serum-creatinine,
serum cystatin-C, estimated glomerular filtration rate (eGFR) using the
Modification of Diet in Renal Disease (MDRD) formula, and estimated creatinine
clearance rate (eCCr) using the Cockcroft-Gault formula were measured just before
and 16-80 hr after MRI. Groups were compared statistically by Mann-Whitney U
tests and Wilcoxon signed-rank tests. There were no significant differences in
clinical characteristics between the gadodiamide (n = 43) and gadopentetate (n =
59) groups. Serum-creatinine, eGFR and eCCr before and 16-80 hr after MRI did not
differ significantly within either group or between the two groups. Serum
cystatin-C was significantly higher 16-80 hr after than before MRI only in the
gadodiamide group (0.79 +/- 0.21 vs. 0.74 +/- 0.14 mg/L, p = 0.028). The ionic
contrast medium, gadopentetate, did not affect renal function during MRI, whereas
the nonionic contrast medium, gadodiamide, affected renal function transiently.
PMID- 28496046
TI - Soluble Vascular Cell Adhesion Molecule and Cardiovascular Disease: An
Epidemiological View.
PMID- 28496045
TI - Cholic Acid Enhances Visceral Adiposity, Atherosclerosis and Nonalcoholic Fatty
Liver Disease in Microminipigs.
AB - AIM: We have recently established a novel swine model for studies of
atherosclerosis using MicrominipigsTM (uMPs) fed a high-fat/high-cholesterol diet
(HcD). Using this swine model, we re-evaluated the effects of dietary cholic acid
(CA) on serum lipid profile, atherosclerosis and hepatic injuries. METHODS: The
uMPs were fed HcD supplemented with 0.7% CA (HcD+CA) for eight weeks, and the
effect of CA on serum lipoprotein levels, expression of oxidative stress markers,
adiposity and lesion formation in the aorta, liver, and other organs was
investigated. RESULTS: The HcD+CA-fed group exhibited more visceral adiposity,
progression of atherosclerosis and higher serum levels of oxidative stress
markers than the HcD-fed group, even though they showed similar serum lipid
levels. The liver demonstrated increased lipid accumulation, higher expression of
oxidative stress markers, accelerated activation of foamy Kupffer cells and
stellate cells, and increased hepatocyte apoptosis, indicating non-alcoholic
fatty liver disease (NAFLD). Intriguingly, foamy macrophage mobilization was
observed in various organs, including the reticuloendothelial system, pulmonary
capillary vessels and skin very often in HcD+CA-fed uMPs. CONCLUSION: To our
knowledge, this is the first large animal model, in which visceral obesity, NAFLD
and atherosclerosis are concomitantly induced by dietary manipulation. These data
suggest the detrimental effects of CA, potentially through local and systemic
activation of oxidative stress-induced signaling to macrophage mobilization, on
the acceleration of visceral adiposity, atherosclerosis and NAFLD.
PMID- 28496047
TI - Histopathology of Asymptomatic Iliac Atherosclerosis: From Autopsy to Practice.
PMID- 28496048
TI - Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors and Stroke.
PMID- 28496049
TI - Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors and Stroke - Reply.
PMID- 28496050
TI - Multiple system atrophy: clinicopathological characteristics in Japanese
patients.
AB - Multiple system atrophy (MSA) is an adult-onset neurodegenerative disorder that
has both clinical and pathological variants. Clinical examples include MSA with
predominant cerebellar ataxia (MSA-C) and MSA with predominant parkinsonism (MSA
P), whereas olivopontocerebellar atrophy and striatonigral degeneration represent
pathological variants. We performed systematic reviews of studies that addressed
the relative frequencies of clinical or pathological variants of MSA in various
populations to determine the clinicopathological characteristics in Japanese MSA.
The results revealed that the majority of Japanese patients have MSA-C, while the
majority of patients in Europe and North America have MSA-P. A comparative study
of MSA pathology showed that the olivopontocerebellar-predominant pathology was
more frequent in Japanese MSA than in British MSA. Demonstrated differences in
pathological subtype thus appear consistent with differences in the clinical
subtype of MSA demonstrated between Japan and European populations. We concluded
that olivopontocerebellar-predominant pathology and MSA-C may represent
clinicopathological characteristics in Japanese MSA. Factors determining
predominant involvement of olivopontocerebellar regions in MSA should therefore
be explored.
PMID- 28496051
TI - Molecular investigations of development and diseases of the brain of higher
mammals using the ferret.
AB - The brains of higher mammals such as primates and carnivores contain well
developed unique brain structures. Uncovering the physiological functions,
developmental mechanisms and evolution of these brain structures would greatly
facilitate our understanding of the human brain and its diseases. Although the
anatomical and electrophysiological features of these brain structures have been
intensively investigated, our knowledge about their molecular bases is still
limited. To overcome this limitation, genetic techniques for the brains of
carnivores and primates have been established, and molecules whose expression
patterns correspond to these brain structures were identified recently. To
investigate the functional roles of these molecules, rapid and efficient genetic
manipulation methods for higher mammals have been explored. In this review,
recent advances in molecular investigations of the brains of higher mammals are
discussed, mainly focusing on ferrets (Mustela putorius furo).
PMID- 28496052
TI - Data management issues in mobile ad hoc networks.
AB - Research on mobile ad hoc networks (MANETs) has become a hot research topic since
the middle 1990's. Over the first decade, most research focused on networking
techniques, ignoring data management issues. We, however, realized early the
importance of data management in MANETs, and have been conducting studies in this
area for 15 years. In this review, we summarize some key technical issues related
to data management in MANETs, and the studies we have done in addressing these
issues, which include placement of data replicas, update management, and query
processing with security management. The techniques proposed in our studies have
been designed with deep considerations of MANET features including network
partitioning, node participation/disappearance, limited network bandwidth, and
energy efficiency. Our studies published in early 2000's have developed a new
research field as data management in MANETs. Also, our recent studies are
expected to be significant guidelines of new research directions. We conclude the
review by discussing some future directions for research.
PMID- 28496054
TI - Days weaving the lagging strand synthesis of DNA - A personal recollection of the
discovery of Okazaki fragments and studies on discontinuous replication
mechanism.
AB - At DNA replication forks, the overall growth of the antiparallel two daughter DNA
chains appears to occur 5'-to-3' direction in the leading-strand and 3'-to-5'
direction in the lagging-strand using enzyme system only able to elongate 5'-to
3' direction, and I describe in this review how we have analyzed and proved the
lagging strand multistep synthesis reactions, called Discontinuous Replication
Mechanism, which involve short RNA primer synthesis, primer-dependent short DNA
chains (Okazaki fragments) synthesis, primer removal from the Okazaki fragments
and gap filling between Okazaki fragments by RNase H and DNA polymerase I, and
long lagging strand formation by joining between Okazaki fragments with DNA
ligase.
PMID- 28496053
TI - Chemical and structural biology of protein lysine deacetylases.
AB - Histone acetylation is a reversible posttranslational modification that plays a
fundamental role in regulating eukaryotic gene expression and chromatin
structure/function. Key enzymes for removing acetyl groups from histones are
metal (zinc)-dependent and NAD+-dependent histone deacetylases (HDACs). The
molecular function of HDACs have been extensively characterized by various
approaches including chemical, molecular, and structural biology, which
demonstrated that HDACs regulate cell proliferation, differentiation, and
metabolic homeostasis, and that their alterations are deeply involved in various
human disorders including cancer. Notably, drug discovery efforts have achieved
success in developing HDAC-targeting therapeutics for treatment of several
cancers. However, recent advancements in proteomics technology have revealed much
broader aspects of HDACs beyond gene expression control. Not only histones but
also a large number of cellular proteins are subject to acetylation by histone
acetyltransferases (HATs) and deacetylation by HDACs. Furthermore, some of their
structures can flexibly accept and hydrolyze other acyl groups on protein lysine
residues. This review mainly focuses on structural aspects of HDAC enzymatic
activity regulated by interaction with substrates, co-factors, small molecule
inhibitors, and activators.
PMID- 28496057
TI - Optical Elemental Analysis of Metals Using Shewanella oneidensis.
AB - A simple method for the detection of metal ions in solution is proposed, using
Shewanella oneidensis, which has the ability to reduce metal ions into metal
nanoparticles on the cell surface. The method can be used to identify metal ions
in solution using the light-scattering characteristics of the metal nanoparticles
formed on the cells.
PMID- 28496056
TI - Stat3 inhibitor abrogates the expression of PD-1 ligands on lymphoma cell lines.
AB - Recent studies have indicated the significance of immune checkpoint molecules
including programmed death-1 (PD-1), cytotoxic T-lymphocyte associated protein 4,
and T-cell immunoglobulin and mucin domain-containing molecule-3 for anti-tumor
immune responses. We previously investigated PD-1 ligand 1/2 (PD-L1/2) expression
in lymphoma cell lines, and found that PD-L1/2 is expressed on the adult T-cell
leukemia/lymphoma (ATL-T) and B-cell lymphoma (SLVL) cell lines. In the present
study, we investigated whether the Stat3 inhibitor WP1066 abrogated PD-L1/2
expression in lymphoma cell lines. Incubation with WP1066 inhibited lymphoma cell
growth and induced cell apoptosis. PD-L1/2 expression in the ATL-T, SLVL, and
human brain malignant lymphoma (HKBML) cell lines was significantly abrogated by
WP1066 treatment. These data indicated that a Stat3 inhibitor abrogated PD-L1/2
expression in lymphoma cells. Such an inhibitor is therefore considered to be
useful for additional immunotherapy in patients with advanced lymphoma.
PMID- 28496055
TI - Organization and dynamics of yeast mitochondrial nucleoids.
AB - Mitochondrial DNA (mtDNA) is packaged by association with specific proteins in
compact DNA-protein complexes named mitochondrial nucleoids (mt-nucleoids). The
budding yeast Saccharomyces cerevisiae is able to grow either aerobically or
anaerobically. Due to this characteristic, S. cerevisiae has been extensively
used as a model organism to study genetics, morphology and biochemistry of
mitochondria for a long time. Mitochondria of S. cerevisiae frequently fuse and
divide, and perform dynamic morphological changes depending on the culture
conditions and the stage of life cycle of the yeast cells. The mt-nucleoids also
dynamically change their morphology, accompanying morphological changes of
mitochondria. The mt-nucleoids have been isolated morphologically intact and
functional analyses of mt-nucleoid proteins have been extensively performed.
These studies have revealed that the functions of mt-nucleoid proteins are
essential for maintenance of mtDNA. The aims of this review are to summarize the
history on the research of yeast mt-nucleoids as well as recent findings on the
organization of the mt-nucleoids and mitochondrial dynamics.
PMID- 28496058
TI - Derivatization-based High-throughput Bioanalysis by LC-MS.
AB - Liquid chromatography coupled with mass spectrometry (LC-MS) is one of the most
prominent analytical techniques due to its inherent selectivity and sensitivity.
LC-MS is currently the first choice for high-throughput bioanalysis due to the
advancements in MS instruments and the analytical software. Based on this
situation, we are developing various types of derivatization reagents, including
chiral reagents for MS and/or MS/MS detection. These developed reagents are
adopted for the detection of biomarker candidates related to diseases. The
biomarker candidates include not only achiral molecules, but also chiral ones.
Although determining the already-identified chiral molecules is relative easy, it
is very difficult to identify and/or determine unknown enantiomer(s) in real
samples. To solve this difficulty, we proposed a new strategy to identify unknown
enantiomeric biomarkers related to diseases. This review paper deals with the
development of derivatization reagents for amines and carboxylic acids in LC-MS
analysis and their application to bioanalysis.
PMID- 28496059
TI - Rapid Photoluminescence Quenching Based Detection of Cu2+ in Aqueous Medium by
CdS Quantum Dots Surface Passivated by Thiourea.
AB - Presented here is a simple yet rapid and efficient analytical method for visual
as well as spectroscopic method for sensing of trace concentrations of Cu2+ ions
in aqueous medium by systematic photoluminescence quenching of a highly water
soluble probe made of CdS quantum dots surface modified by thiourea. The salient
features of this work describe rapid detection (2 min equilibration time) of Cu2+
ions at wider linear concentration range (0.025 - 10 mg/L) corresponding to a
sensitivity of 2.81(mg/L)-1 and limit of quantification of 47.3 MUg/L,
respectively, suitable for Cu2+ sensing in drinking water and ground water.
Further, the detection of Cu2+ ion was free from most interfering cations and
anions, except for minor interference from Cr3+, Hg2+ and Pb2+. The robustness of
our probe for Cu2+ sensing is demonstrated from efficient Cu2+ spike recovery
analysis in groundwater and river water samples.
PMID- 28496061
TI - Application of Electron Paramagnetic Resonance and Solid-state 13C Nuclear
Magnetic Resonance of Cross-polarization/Magic Angle Spinning to Study Enzymatic
Degradation of Silk Fabrics.
AB - The enzymatic degradation of silk by protease XIV has been investigated by using
scanning electron microscopy (SEM), Fourier transfer infrared spectroscopy
(FTIR), solid-state 13C nuclear magnetic resonance of cross-polarization/magic
angle spinning (13C CP/MAS solid state NMR) and electron paramagnetic resonance
(EPR). Micro-morphology of protease XIV aged samples showed that microfilaments
were stripped out from the surface of silk fibers. The results of FTIR and 13C
CP/MAS solid-state NMR indicated that the enzymatic degradation process could be
divided into two stages. The EPR spectra indicated that the enzymatic degradation
process was related to the free radical with the g-factor value of 2.0043. We
also proposed that at the first degradation stage, the free radicals were apt to
lose activities due to the loose structure of the non-crystalline region; at the
second degradation stage, the free radicals produced in the crystalline region
tended to be stored.
PMID- 28496060
TI - Rapid Detection of Small Molecule Metabolites in Serum of Hepatocellular
Carcinoma Patients Using Ultrafast Liquid Chromatography-Ion Trap-Time of Flight
Tandem Mass Spectrometry.
AB - A method was developed for analyzing broad spectrum small molecule metabolites in
the serum of hepatocellular carcinoma (HCC) patients based on ultrafast liquid
chromatography-ion trap-time of flight tandem mass spectrometry (UFLC-IT-TOF MS).
Serum samples were collected from 80 HCC patients and healthy persons. After
pretreatment process for protein precipitation, the supernatant was analyzed with
the UFLC-IT-TOF MS to obtain information on the metabonomics of small molecules.
The eight compounds of glycocholic acid, choline glycerophosphate, acetyl-L
phenylalanine, oleamide, tetradecanamide, acetylcarnitine, lysolecithin and
glycochenodeoxycholic acid in the HCC group were identified with significant
differences from those in the health group (P <0.01). By using multidimensional
analysis of variation coefficient and principal component analysis for the
repeatability and 48 h stability, the method was demonstrated to have good
repeatability, excellent precision, and high stability, which can satisfy the
metabonomics research requirement. The high throughput and practical usability of
the method further shows perspective for metabonomic analysis of large-batch
serum samples.
PMID- 28496062
TI - A Novel Electrochemical Sensor Based on [Ru(NH3)6]Cl3 as a Redox Indicator for
the Detection of G-G Mismatched DNA.
AB - In this paper, a novel electrochemical sensor was developed for the rapid
detection of G-G mismatched DNA based on hexaammineruthenium(III) chloride
([Ru(NH3)6]Cl3) as a redox indicator. The sensor platform was constructed by
immobilizing small molecules (NC-linker) on the gold electrode via amide bonds.
The as-prepared NC-linker as the nucleic acids recognition molecule can interact
with the G base of DNA. After the sensor was incubated with G-G mismatched DNA,
the double-stranded DNA (dsDNA) acted as carriers of the signal tags
[Ru(NH3)6]Cl3, which resulted in a remarkable electrochemical signal. More
binding of [Ru(NH3)6]Cl3 led to increases of the electrochemical signal. Other
mismatched DNA produced only a low response, as well as complementary DNA. Thus G
G mismatched DNA can be easily discriminated from other mismatched and
complementary DNA based on the sensor. Furthermore, the method was simple, rapid
and repeatable for the detection of G-G mismatched DNA. The selective detection
of target dsDNA was achieved by a relative current ratio of the target and
control DNA. These results demonstrated that this strategy could provide great
promise for the rapid and specific detection of other sequence-specific DNA.
PMID- 28496063
TI - Fabrication of Water-soluble Fluorescent Polymeric Micelles for Selective
Detection of Hg2+ in Blood Serum.
AB - In this study, amphiphilic diblock copolymers were designed and synthesized via
the incorporation of reversible addition-fragmentation chain transfer radical
polymerization (RAFT) and a subsequent grafting technique. Subsequently, Hg2+
sensitive water-soluble fluorescent polymeric micelles (FNs) were prepared by a
reprecipitation strategy. The spectroscopic characteristics demonstrate that the
fluorescein isothiocyanate (FITC) was successfully linked into the polymer. Due
to the promoted reaction of desulfurization cyclization by Hg2+, the fluorescence
of fluorescein in FNs was obviously quenched. The as-prepared FNs showed
admirable Hg2+-sensitivity (detection limit: 54 nM), excellent water-solubility
and high selectivity. In addition, FNs were successfully used to determine Hg2+
in blood serum. We expected that the as-prepared FNs could perform potential
applications in imaging, sensing, and bioanalytic chemistry.
PMID- 28496064
TI - Colorimetric Ion Sensors Based on Polystyrenes Bearing Side Chain Triazole and
Donor-Acceptor Chromophores.
AB - Side chain clicked polystyrene derivatives formed by the Cu(I)-catalyzed azide
alkyne cycloaddition (CuAAC) reaction showed colorimetric ion sensing behaviors
when donor-acceptor chromophores, prepared by a [2+2] cylcoladdition
retroelectrocyclization between electron-rich alkynes and tetracyanoethylene
(TCNE)/7,7,8,8-tetracyanoquinodimethane (TCNQ), were attached to the triazole
rings. The metal ion sensing behaviors could be explained according to the theory
of hard and soft acids and bases (HSAB). Hard acidic metal ions were mainly
recognized by the hard basic anilino-nitrogen moieties, resulting in a decrease
in the charge-transfer (CT) bands. In contrast, soft acidic metal ions led to a
bathochromic shift in the CT bands due to the selective interactions with the
soft basic cyano-nitrogen atoms. With the triazole spacers, more soft (and/or
borderline) metal ions were recognized by the donor-acceptor chromophores
probably due to more space for the various sized metal ions. The chemodocimetric
anion sensing behaviors of the clicked polystyrenes were almost the same as those
of the counter polystyrenes without the triazole spacers. Overall, the triazoles
in this study do not serve as colorimetric sensor units towards both metal ions
and anions, but they are effective spacers between the polymer main chain and ion
sensing donor-acceptor side chain chromophores.
PMID- 28496065
TI - Solid Sampling in Analysis of Soils by Two-jet Plasma Atomic Emission
Spectrometry.
AB - The possibility of direct analysis of soils by two-jet plasma atomic emission
spectrometry was investigated using certified reference materials of black earth,
grey desert and red soils. It was shown that As, B, Cd, Cu, Hg, P, and V could be
determined after a 2-fold, and Be, Co, Cr, Ga, Nb, Pb, and Zn-after a 10-fold
dilution of the samples by a spectroscopic buffer using calibration samples based
on graphite powder. The strongest matrix effects were revealed for red soil
having the highest Al and Fe concentration, which led to the overstated
concentrations of some elements. The overstating factor depended on analyte
concentration and was no more than 2. A clear advantage of the suggested
technique over existing methods is the simple sample preparation process, which
requires no reagents except a spectroscopic buffer, and possibility of using the
same calibration samples for analysis of different soils.
PMID- 28496066
TI - Application of Deep Eutectic Solvents in Hybrid Molecularly Imprinted Polymers
and Mesoporous Siliceous Material for Solid-Phase Extraction of Levofloxacin from
Green Bean Extract.
AB - Deep eutectic solvents (DES) are potential ecofriendly surfactants for the
preparation of materials. In this study, both molecularly imprinted polymers
(MIPs) and mesoporous siliceous materials (MSMs) were modified by betaine-based
DES. Six materials were employed as solid phase extraction (SPE) adsorbents for
the rapid purification of levofloxacin. The DES-based materials showed better
selective adsorption than the conventional materials. The adsorption curves of
DES-MIP showed superior molecular recognition ability and binding capability for
levofloxacin compared to the other materials. The limit of detection and limit of
quantitation of the method were 0.01 and 0.03 MUg/mL for levofloxacin,
respectively. The method recoveries at three spiked levels were 97.2 - 100.2% for
DES-MIP, with an RSD <1.8%. DES-MIP showed the highest selective recovery (95.2%)
for levofloxacin from the green bean extract, and could remove the interferent
effectively.
PMID- 28496067
TI - Retention Behavior of Inorganic Anions in Hydrophilic Interaction Chromatography.
AB - The retention behavior of inorganic anions was studied in hydrophilic interaction
chromatography (HILIC). In this study, five kinds of HILIC stationary phases
(amino, imidazole, amide, pyridine and zwitterionic) were investigated. It was
found that only amino and imidazole columns exhibited the separation of inorganic
anions under HILIC conditions. The retention mechanism was further investigated
under both columns. A reversed elution order of inorganic anions was observed
under the HILIC condition compared with those observed under the ion-exchange
chromatography mode (IEC). The effect of salt species and their concentration in
the eluent were investigated under constant acetonitrile (ACN) content. Sodium
chloride and sodium perchlorate were chosen as the salt, and the salt (sodium
perchlorate) concentration was varied from 10 to 40 mM to confirm the effect of
the electrostatic interaction. The slope values of the plots of the log retention
factor (k) versus the log eluent concentration were calculated to be between
0.43 and -0.45 for the amino column, while those obtained on the imidazole column
were between -0.68 and -0.73. Various concentrations of ACN were also examined
with 20 mM sodium perchlorate, and the typical HILIC retention behavior was
observed on both amino and imidazole columns. Due to the obtained results, it is
considered that the separation of inorganic anions under the HILIC condition was
achieved by both electrostatic interaction and partition.
PMID- 28496068
TI - The Use of a Gas Chromatography/Milli-whistle Technique for the On-line
Monitoring of Ethanol Production Using Microtube Array Membrane Immobilized Yeast
Cells.
AB - Hollow, poly(L-lactic acid) microtube array membranes (MTAM) were used in
preparing membranes that contained immobilized yeast cells. To evaluate the
performance of the developed system for continuous and fed-batch fermentation, a
gas chromatography/milli-whistle device was used to on-line monitor the
production of ethanol. The milli-whistle was connected to the outlet of a GC
capillary, and when the fermentation gases and the GC carrier gas passed through
it, a sound with a fundamental frequency was produced. The online data obtained
for frequency-change vs. retention time can be recorded after a fast Fourier
transform. In typical bioethanol fermentation, the yeast cells cannot be
recycled, whereas the artificial yeast-MTAMs can be. The hollow-MTAM containing
immobilized yeast cells significantly enhanced to bioethanol productivity, and
represent a novel, promising technology for bioethanol fermentation. Our data
indicate that the gas chromatography/milli-whistle device, which is economical
and stable, is a very useful detector for long-term monitoring.
PMID- 28496069
TI - Optimization and Investigation of Zwitterionic Monolithic Stationary Phases for
Capillary Ion Chromatography.
AB - Zwitterionic monolithic columns were synthesized by a one-pot reaction using [2
(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide, ethylene
dimethacrylate, methanol and 2,2'-azobis(isobutyronitrile) as the monomer, cross
linker, porogen and initiator, respectively. The optimum conditions for
polymerization and the efficiency of the prepared columns were examined for ion
chromatography. The separation of five kinds of inorganic anions was achieved.
The back pressures were monitored as increasing flow-rate, and the resulting
plate heights (i.e. height equivalent of a theoretical plate, HETP) of SCN- were
calculated at the inspected flow-rates. It was found that the increment rates of
both the back pressure and HETP were rather slight. Mobile phases containing
various cations or acid increased the retention times of the anions. Divalent
cations could be separated, while monovalent cations could not be resolved due to
their weak retention on the stationary phases.
PMID- 28496070
TI - Trace Elemental Determination Using a Portable Total Reflection X-Ray
Fluorescence Spectrometer with a Collodion Film Sample Holder.
AB - Using a portable total-reflection X-ray fluorescence (TXRF) spectrometer with a
collodion film sample holder, a spectrum of an analyte containing 50 ng of
aluminum was measured. The Al Kalpha line (1.49 keV) that partially overlaps with
the Si Kalpha line (1.74 keV) from a quartz glass substrate usually used as a
sample holder for TXRF analysis, was clearly detected when using the collodion
film sample holder. To investigate the quantitative performance of the portable
spectrometer with a collodion film sample holder, the concentrations of Cr, Mn,
and Fe in a certified reference material of river water (JSAC 0302-3b), whose
certified values are 10.0, 5.1, and 59.6 MUg/L, respectively, were determined by
the internal-standard method. We showed that approximate concentrations of these
elements were determined.
PMID- 28496071
TI - Solubility-based Separation and Purification of Long-Chain Chitin
Oligosaccharides with an Organic-Water Mixed Solvent.
AB - A simple and rapid method for separation and purification of chitin
oligosaccharides, (GlcNAc)n, with n >= 5 is presented. A commercially available
chitin oligosaccharides sample, consisting of (GlcNAc)n with n = 1 - 7, was used
as the starting material. Ten milligrams of the material was mixed with 100 MUL
of the 1 mol/L HCl. All the (GlcNAc)n species were dissolved in the aqueous
medium. The aqueous solution was mixed with 900 MUL of EtOH; the mixture was
centrifuged, and the supernatant was removed to obtain a precipitate. The
precipitate was found to consist mainly of (GlcNAc)n with n >= 5, indicating the
significant difference in solubility between the short-chain (GlcNAc)n species
with n <= 3 and the longer ones. By the repetition of the operations, a high
purity long-chain (GlcNAc)n sample with n >= 5 could be prepared successfully.
Since the long-chain (GlcNAc)n species are known to have excellent elicitor
activity, this sample would be useful in the study of plant pathology, as well as
chitin and chitosan chemistry.
PMID- 28496072
TI - Improvement of Chromium(VI) Extraction from Acidic Solutions Using a Poly(vinyl
chloride)-based Polymer Inclusion Membrane with Aliquat 336 as the Carrier.
AB - An important reason for the inefficient extraction of Cr(VI) from its acidic
solutions into polymer inclusion membranes (PIMs), consisting of poly(vinyl
chloride) as the base-polymer and Aliquat 336 as the carrier, was found to be
associated with the leaching of Aliquat 336 from the PIMs into the solutions,
where it subsequently reduced the anionic Cr(VI) species to cationic Cr(III)
species. The PIM extraction efficiency for Cr(VI) was significantly improved by
the addition of NaNO3 to the solutions, which suppressed the leaching of Aliquat
336 and the reduction of Cr(VI) to Cr(III).
PMID- 28496073
TI - Mass Transfer in Mesoporous Microparticles Studied by Confocal Fluorescence
Recovery after Photobleaching.
AB - The intraparticle diffusion of a fluorescent dye in single microparticles in an
aqueous solution was analyzed using fluorescence recovery after photobleaching,
with a confocal fluorescence microscope. The fluorescence depth profile of single
microparticles, and the fluorescence recovery at the particle center, were
measured; further, the intraparticle diffusion coefficient was determined through
simulations of three-dimensional diffusion in the respective microparticles. The
intraparticle diffusion of coumarin 102 in octadecylsilyl silica gel was limited
by the surface diffusion.
PMID- 28496075
TI - Determination of Fasting and Non-Fasting Cholesterol Levels of Low- and High
Density Lipoproteins with Homogenous Assays: A Promising Reliable Way to
Assessment of Dyslipidemia.
PMID- 28496076
TI - [Early Results of Complex Fractionated Atrial Electrogram Mapping Guided Atrial
Fibrillation Surgery].
AB - OBJECTIVE: Although the Cox-maze operation is the standard surgical procedure for
permanent atrial fibrillation(AF), conversion to sinus rhythm is limited by
patient characteristics, including the duration of AF, atrial size, and voltage
of fibrillation waves. A surgical strategy based on structural alteration of the
electrical substrates of AF is required to achieve better outcomes of AF surgery.
Complex fractionated atrial electrogram (CFAE) plays an important role in the
electrical substrate of AF. We performed AF surgery guided by preoperative CFAE
mapping using a 3-dimensional (3D) mapping system. This study evaluated the early
results of our procedure. METHODS: From January 2015 to August 2016, 8 patients
(mean age:66.5+/-6.4 years) underwent CFAE mapping-guided AF surgery. In the
preoperative electrophysiological study using 3D mapping, CFAE was defined by a
low voltage electrogram (0.05~0.25 mV) with a highly fractionated potential
(short cycle length <120 msec). First, right atrial CFAE sites were ablated by
using a catheter ablation system. Several days after right-sided CFAE ablation, a
modified Cox-maze operation was performed with additional cryoablation of CFAE
sites. RESULTS: There were 1~3 (mean:2.5 +/-0.8) CFAE sites in the right atrium
and 2~4 (mean:2.4+/-0.7) sites in the left atrium. Mean CFAE mapping time was
87.6+/-24.6 minutes, fluoroscopy time was 53.1+/-22.2 minutes, and volume of
contrast agent was 44+/-3 ml. Concomitant cardiac surgery included mitral valve
plasty in 6 patients, and aortic valve replacement and mitral valve replacement
in 1 patient each. The mean time for CFAE mapping-guided AF surgery was 25.7+/
5.6 minutes. At discharge, 7 patients were in sinus rhythm and 1 patient still
had AF, but sinus rhythm recovered at 3 months postoperatively without anti
arrhythmic medication. After a mean follow-up of 11.7+/-8.5 months, all patients
remained in sinus rhythm. CONCLUSIONS: Early results suggest that CFAE mapping
guided atrial fibrillation surgery is feasible and effective. Although the long
term effect of CFAE ablation on maintenance of sinus rhythm and atrial function
should be evaluated, this novel method could provide an alternative strategy for
the surgical treatment of AF.
PMID- 28496077
TI - [Surgical Training Utilizing Swine Under General Anesthesia and Animal Ethics].
AB - A cross-sectional study is conducted with primary residents attended wet labs at
Tohoku University Hospital Advanced Medical Training Center in order to
investigate the efficacy of the training, especially focused on the animal
ethics. The 41 participants answered questionnaires in regard to non-technical
skills, technical skills and ethics before and after the practice. To identify
differences in each ethical question between 2 time points, Wilcoxon signed ranks
test was used because the data was not normally distributed. As the result of it,
all animal ethical questions showed significant differences(0.0016<=p<=0.0380,
alpha=0.05 level of significance). Beside them, only 1 out of 5 general ethical
questions showed it (p=0.0137). This outcome verified that the lecture of animal
ethics and the observation of animal care in this center fixed in the training
curriculum clearly induced participants' psychological movements.
PMID- 28496078
TI - [Trial of the Profit Optimization of the Department of Cardiac Surgery in the
Local National University Hospital].
AB - In recent years economic sense is required in hospital management, the national
university hospital is also no exception. We performed duty improvement efforts
as well as the current state analysis in the department of cardiac surgery for
the purpose of revenue optimization in our hospital. At result, we succeeded in
the improvement of the medical index as well as medical profit and found the key
of solution to the serious problem that national university hospital has.
PMID- 28496079
TI - [Surgical Treatment for Anomalous Aortic Origin of Coronary Arteries].
AB - Anomalous aortic origin of coronary arteries is rare. We report 3 cases of
surgical treatment for anomalous aortic origin of coronary arteries. Case 1 was a
38-year-old man who was saved by the use of an automated external defibrillator
from cardiopulmonary arrest while exercising. The coronary angiogram showed the
right coronary artery arising from the left coronary sinus of Valsalva and being
located between the aorta and the pulmonary trunk. He underwent coronary artery
bypass grafting (CABG) using the right internal thoracic artery with ligation of
proximal part of right coronary artery to prevent sudden death. Case 2 was a 76
year-old woman with the left coronary artery arising from the right coronary
sinus of Valsalva and proximal left anterior descending coronary artery stenosis.
She underwent CABG. Case 3 was a 58-year-old man with severe aortic valve
regurgitation. He underwent aortic valve replacement. During weaning from
cardiopulmonary bypass, the electrocardiogram revealed ST-segment elevation.
Transesophageal echocardiography showed intramural segment of the left coronary
artery and obstruction of the left coronary blood flow. Repair was accomplished
by unroofing the intramural segment. All the cases were successfully treated by
surgical treatment.
PMID- 28496081
TI - [Salvage Surgery Following Chemoradiotherapy for Thymic Basaloid Cell Carcinoma].
AB - We performed salvage surgery after chemoradiotherapy(CRT) in a patient with
thymic basaloid cell carcinoma. A 46-year-old man with an abnormal chest shadow
on X-ray findings was referred to our hospital. Computed tomography revealed a
partially solid tumor along with a multilocular cyst in the anterior mediastinum
with mediastinal lymph node swelling infiltrating to the superior vena cava(SVC).
Positron emission tomography revealed FDG accumulation (SUVmax 7.94)in the tumor.
Pathological findings of a tumor biopsy specimen obtained by thoracoscopy led to
a diagnosis of thymic basaloid cell carcinoma. Following CRT (ADOC+RT:60 Gy), a
complete resection (R0)with replacement of the SVC was performed. The
postoperative course was uneventful, and the patient was alive at 20 months after
surgery with metastasis to the cervical lymph nodes and bone.
PMID- 28496080
TI - [Surgical Experience of Infective Aneurysm of Brachial Artery Complicated with
Infective Mitral Valve Endocarditis].
AB - We report a rare case of aneurysmal formation of the left brachial artery
complicated with infective endocarditis of the mitral valve. A 67-year-old man
was referred to our institution for further examination of pulsatile mass at the
left upper extremity. Computed tomography showed a left brachial arterial
aneurysm with a diameter of 4 cm and gradual expansion of the aneurysm was also
recognized. Furthermore, echocardiography revealed severe mitral valve
regurgitation with a vegetation. There was no feature of congestive heart
failure. He was diagnosed with subacute infective endocarditis and infective left
brachial arterial aneurysm. Considering these clinical findings, staged surgical
treatment was planned. He underwent resection of the brachial arterial aneurysm
and bypass grafting with an autologous saphenous vein on an urgent basis. One
month after the initial operation, elective mitral valve plasty was successfully
performed. Although aneurysmal formation of the brachial artery subsequent to
infective endocarditis is rare, we should keep this potentially serious
complication in mind.
PMID- 28496083
TI - [Retrograde Type A Aortic Dissection after Thoracic Endovascular Aortic
Repair;Report of a Case].
AB - A 72-year-old man presented with aneurysms of the distal aortic arch and the
distal descending aorta due to chronic type B aortic dissection. We first
performed thoracic endovascular aortic repair (TEVAR) in the distal descending
aorta, and the aneurysm was successfully excluded using a Gore Tag stentgraft.
Seven days after TEVAR, computed tomography revealed retrograde type A aortic
dissection occurring from the ascending aorta to the distal aortic arch. In
emergency surgery, ascending aorta and total arch replacement were performed
under selective cerebral perfusion with moderate hypothermia, and after coming
off cardiopulmonary bypass, the distal aortic arch aneurysm was excluded using a
Gore Tag stentgraft.
PMID- 28496082
TI - [Slowly progressive Basaloid Squamous Cell Carcinoma of the Lung].
AB - Basaloid squamous cell carcinoma (BSC) of the lung is a rare variant of squamous
cell carcinoma (SCC) and is reported to show poor prognosis. A 70-year-old man
presented to the clinic complaining of a productive cough. Computed tomography(
CT) of the chest revealed a nodule in the left lower lobe of the lung. A
bronchoscopy and transbronchial lung biopsy(TBB) were performed twice;no evidence
of malignancy was found. So we followed up by periodic chest CT. One year and 4
months after the 1st visit, the nodule increased in size from 14 to 19 mm. TBB
was performed again and the tumor was diagnosed as SCC. The patient underwent a
left lower lobectomy and the tumor was diagnosed as BSC by postoperative
pathological examination. Two years and 6 months after surgery, no recurrence has
been observed in the patient.
PMID- 28496084
TI - [Redissection of the Aortic Root Three Months after Replacement of the Ascending
Aorta for Acute Stanford Type A Dissection;Report of a Case].
AB - We report a case of redissection of the aortic root after graft replacement for
acute aortic dissection using BioGlue to approximate the false lumen. A 49-year
old man underwent graft replacement of the ascending aorta for acute aortic
dissection. In this operation, BioGlue was applied to the false lumen of the
aortic root. Three months later, computed tomography revealed an ulcer-like
projection and an intramural hematoma in the aortic root. Aortic root replacement
was performed, in which operative findings showed a new intimal tear and a patent
false lumen contained with hematomas and a fragment of BioGlue. Histological
examination showed no evidence of adhesion between the intimal media and the
adventitia of the aorta, or toxic effect of BioGlue. We conclude that care should
be taken in applying the BioGlue to a false lumen and that cautious follow-up is
mandatory not to overlook redissection.
PMID- 28496085
TI - [Graft Pseudoaneurysm after Ascending to Abdominal Aorta Bypass for Atypical
Coarctation Due to Aortitis Syndrome;Report of a Case].
AB - We present a case of a 44-year-old woman, with pseudoaneurysm formation at the
middle of the prosthetic graft, 60 mm in diameter. She had been diagnosed with
atypical coarctation due to aortitis 27 years before, and had undergone a bypass
operation with 14 mm-diameter Cooley double velour graft from the ascending aorta
to the abdominal aorta. This time, endovascular aortic repair was performed to
prevent rupture of the pseudoaneurysm. Though a knitted Dacron graft has a risk
of psuedaneurysm formation long patency could be obtained when used in ascending
aorta-abdominal aorta bypass.
PMID- 28496086
TI - [Surgical Treatment of Left Main Trunk Coronary Artery Aneurysm with Asymptomatic
Myocardial Ischemia;Report of a Case].
AB - Coronary artery aneurysm is rare, and there is no established protocol for
surgical indication. On preoperative examination of orthopedic surgery, a 76-year
old male was found with asymptomatic myocardial ischemia. Radiological
examinations revealed triple vessel disease and a coronary artery aneurysm, 10 mm
in size, at the bifurcation of the left main trunk. Combined with quintuple
coronary artery bypass grafting, surgical repair of the aneurysm was peformed
under cardiopulmonary bypass on beating heart. Epicardial echocardiography was
used to detect the site and the blood flow on the aneurysm. Postoperative course
was uneventful. Epicardial echocardiography was useful for detecting the coronary
artery aneurysm in the myocardium and the residual aneurysmal blood flow.
PMID- 28496087
TI - [Rupture of an Aneurysm of the Right Sinus of Valsalva Into the
Pericardium;Report of a Case].
AB - A sinus of Valsalva aneurysm is an uncommon cardiac anomaly. The aneurysm usually
ruptures into the cardiac cavity, and rupture into the pericardial cavity is
unusual. A 69-year-old man was admitted to our hospital after collapse due to
cardiac tamponade. Computed tomography revealed a ruptured right sinus of
Valsalva aneurysm (5 cm) with massive pericardial effusion. The right coronary
artery arose from the aneurysm. Severe aortic regurgitation due to the lack of
coaptation of the valves was detected by echocardiography. Emergency patch
closure of the aneurysm orifice, aortic valve replacement, and coronary artery
bypass grafting to the right coronary artery were performed. The postoperative
course was uneventful and the patient was discharged on postoperative day 28 in
good health.
PMID- 28496088
TI - [Lung Abscess with Acute Empyema Which Improved after Performing by Video
Assissted Thoracic Surgery( Including Pneumonotomy and Lung Abscess
Drainage);Report of a Case].
AB - We herein report the case of a patient demonstrating a lung abscess with acute
empyema which improved after performing pnemumonotomy and lung abscess drainage.
A 60-year-old male was referred to our hospital to receive treatment for a lung
abscess with acute empyema. At surgery, the lung parenchyma was slightly torn
with pus leakage. After drainage of lung abscess by enlarging the injured part,
curettage in the thoracic cavity and decortication were performed. The
postoperative course was uneventful. Direct drainage of an abscess into the
thoracic cavity is thought to be a choice for the treatment of lung abscesses.
PMID- 28496089
TI - [Malignant Pleural Mesothelioma Presenting Refractory Pneumothorax Successfully
Treated by Intrapleural Administration of Diluted Fibrin Glue;Report of a Case].
AB - Malignant pleural mesothelioma sometimes accompanies intractable neumothorax due
to the visceral pleural invasion of the tumor. A 68-years-old man was found to
have massive pleural effusion and pleural mass combined with pneumothorax by
computed tomography(CT). CT guided biopsy revealed the mass to be malignant
pleural mesothelioma. Since continuous air leakage was observed by chest
drainage, pleurodesis by OK-432 twice and bronchial occlusion by Endobronchial
Watanabe Spigot (EWS)were performed. But air leakage continued, and the surgery
was performed, however the treatment failed to stop the air leakage. Finally, the
intrapleural administration of diluted fibrin glue was challenged and the air
leakage stopped immediately after the treatment.
PMID- 28496090
TI - [Mediastinal Thyroid Carcinoma;Report of a Case].
AB - 71-year-old woman was pointed out to have an asymptomatic mediastinal tumor.
Chest computed tomography(CT) showed a well-demarcated mass measuring 7 cm in
diameter in the anterior mediastinum. We resected the mass through a median
sternotomy. The tumor had a clear margin without invasion to the surrounding
tissue and did not show continuity with the cervical thyroid gland.
Histopathologically, the tumor was diagnosed as follicular thyroid carcinoma with
capsular invasion. This is an exceptionally rare case.
PMID- 28496091
TI - Mobilization of Hematopoietic Stem Cells for Hematopoietic Cells Autologous
Transplantation with Use of Plerixafor.
AB - BACKGROUND To increase the number of circulating hematopoietic stem cells (HSC)
in the blood, mobilization treatments are currently being used. G-CSF and G-CSF
plus chemotherapy are the most common methods of hematopoietic stem cells
separation used in Poland. MATERIAL AND METHODS We observed patients who failed
an effective hematopoietic stem cell mobilization with G-CSF or with G-CSF plus
chemotherapy. The separation was considered unsuccessful if within a period of 4
consecutive days of separation, the number of obtained CD 34+ cells was lower
than 2.0*10^6/kg of bodyweight. The study involved 32 patients whose CD34+ cells
were collected and the collection for autologous transplantation failed. The
study included 20 men and 12 women. Among all 32 patients, 28 had multiple
myeloma, 3 had DLBCL lymphoma, and 1 had Hodgkin's disease. RESULTS Separation
was unsuccessful in only 3 patients; the remaining 29 achieved an average of
4.83*10^6 CD34+ cells per kg of bodyweight. We conclude that plerixafor is an
important tool in obtaining sufficient quantities of cells for hematopoietic stem
cells separation. CONCLUSIONS The use of plerixafor is a sufficient and safe
option for stem cells mobilization in autologous transplantations.
PMID- 28496092
TI - Usefulness of Contrast-Enhanced Ultrasonography for Predicting Esophageal Varices
in Patients with Hepatitis B Virus (HBV)-Related Cirrhosis.
AB - BACKGROUND The aim of this study was to investigate the usefulness of contrast
enhanced ultrasonography (CEUS) in predicting of esophageal varices (EV) and
assessing high-risk EV in patients with hepatitis B virus (HBV)-related
cirrhosis. MATERIAL AND METHODS Patients with HBV-related cirrhosis who had
undergone endoscopy were prospectively recruited. Hepatic dynamic CEUS was
performed. Regions of interest (ROI) were drawn on the hepatic artery, hepatic
vein, portal vein, and liver parenchyma to measure the corresponding features,
such as arrival times. Spearman's correlation analysis was used to determine the
relations between several dynamic CEUS features and the degree of EV. Receiver
operating characteristics (ROC) curves were constructed to investigate the
diagnostic performance of CEUS in assessing the presence of EV and high-risk EV.
RESULTS Fifty-eight patients (44 men; mean age 51.3 years) were included in this
study. Of these, 18 (31.0%), 12 (20.7%), 11 (19.0%), and 17 (29.3%) of patients
had grade 0, 1, 2, and 3 EV, respectively. Grade 2 and grade 3 EV were considered
high-risk EV. Among the CEUS features, the area under the ROC curves of
intrahepatic transit time (HV-HA, i.e., the difference between hepatic vein
arrival time and hepatic artery arrival time) both for assessment of the presence
of EV and high-risk EV (0.883 and 0.915, respectively) were larger than the other
indices. HV-HA was negatively correlated with the grade of EV. An HV-HA of under
8.2 s indicated the presence of EV and under 7 s indicated high-risk EV.
CONCLUSIONS Dynamic CEUS imaging is useful in assessing the presence of EV and
high-risk EV in patients with HBV-related cirrhosis.
PMID- 28496094
TI - Apical Hypertrophic Cardiomyopathy: Case Report and Literature Review.
AB - BACKGROUND Apical hypertrophic cardiomyopathy (ApHCM) is a relatively rare form
of hypertrophic cardiomyopathy that predominantly affects the apex of the left
ventricle and typically has a nonobstructive physiology. Its variable
presentation and clinical course render ApHCM a commonly delayed or missed
diagnosis. CASE REPORT A 53-year-old Caucasian woman presented with chronic
progressive chest pain. She was initially started on treatment for acute coronary
syndrome. Diagnosis of ApHCM was initially missed on echocardiography, but made
on subsequent cardiac catheterization and cardiac MRI. She improved clinically
with metoprolol, had a work-up for implantable cardioverter-defibrillator
placement, and was referred for genetic testing. CONCLUSIONS Despite earlier
studies suggesting a more benign clinical course of ApHCM, recent studies report
increased morbidity and mortality, which is comparable to the prognosis of other
variants of hypertrophic cardiomyopathy such as hypertrophic obstructive
cardiomyopathy. Thus, when formulating a differential diagnosis for chest pain,
it is important to include structural heart disease including apical and other
variants of hypertrophic cardiomyopathy as part of that differential, as
appropriate management can prevent these devastating sequelae. Furthermore, when
screening tests such as echocardiography cannot adequately establish the
diagnosis of ApHCM, then cardiac MRI or invasive hemodynamic testing is necessary
to establish or refute the diagnosis.
PMID- 28496093
TI - Prediction of New-Onset and Recurrent Atrial Fibrillation by Complete Blood Count
Tests: A Comprehensive Systematic Review with Meta-Analysis.
AB - BACKGROUND Atrial fibrillation (AF) is one of the most critical and frequent
arrhythmias precipitating morbidities and mortalities. The complete blood count
(CBC) test is an important blood test in clinical practice and is routinely used
in the workup of cardiovascular diseases. This systematic review with meta
analysis aimed to determine the strength of evidence for evaluating the
association of hematological parameters in the CBC test with new-onset and
recurrent AF. MATERIAL AND METHODS We conducted a meta-analysis of observational
studies evaluating hematologic parameters in patients with new-onset AF and
recurrent AF. A comprehensive subgroup analysis was performed to explore
potential sources of heterogeneity. RESULTS The literature search of all major
databases retrieved 2150 studies. After screening, 70 studies were analyzed in
the meta-analysis on new-onset AF and 23 studies on recurrent AF. Pooled analysis
on new-onset AF showed platelet count (PC) (weighted mean difference (WMD)=WMD of
-26.39*10^9/L and p<0.001), mean platelet volume (MPV) (WMD=0.42 FL and p<0.001),
white blood cell (WBC) (WMD=-0.005*10^9/L and p=0.83), neutrophil to lymphocyte
ratio (NLR) (WMD=0.89 and p<0.001), and red blood cell distribution width (RDW)
(WMD=0.61% and p<0.001) as associated factors. Pooled analysis on recurrent AF
revealed PC (WMD=-2.71*109/L and p=0.59), WBC (WMD=0.20*10^9/L (95% CI: 0.08 to
0.32; p=0.002), NLR (WMD=0.37 and p<0.001), and RDW (WMD=0.28% and p<0.001).
CONCLUSIONS Hematological parameters have significant ability to predict
occurrence and recurrence of AF. Therefore, emphasizing the potential predictive
role of hematological parameters for new-onset and recurrent AF, we recommend
adding the CBC test to the diagnostic modalities of AF in clinical practice.
PMID- 28496096
TI - Direct atomic scale determination of magnetic ion partition in a room temperature
multiferroic material.
AB - The five-layer Aurivillius phase Bi6TixFeyMnzO18 system is a rare example of a
single-phase room temperature multiferroic material. To optimise its properties
and exploit it for future memory storage applications, it is necessary to
understand the origin of the room temperature magnetisation. In this work we use
high resolution scanning transmission electron microscopy, EDX and EELS to
discover how closely-packed Ti/Mn/Fe cations of similar atomic number are
arranged, both within the perfect structure and within defect regions. Direct
evidence for partitioning of the magnetic cations (Mn and Fe) to the central
three of the five perovskite (PK) layers is presented, which reveals a marked
preference for Mn to partition to the central layer. We infer this is most
probably due to elastic strain energy considerations. The observed increase (>8%)
in magnetic cation content at the central PK layers engenders up to a 90%
increase in potential ferromagnetic spin alignments in the central layer and this
could be significant in terms of creating pathways to the long-range room
temperature magnetic order observed in this distinct and intriguing material
system.
PMID- 28496095
TI - Duration of motherhood has incremental effects on mothers' neural processing of
infant vocal cues: a neuroimaging study of women.
AB - The transition to motherhood, and the resultant experience of caregiving, may
change the way women respond to affective, infant signals in their environments.
Nonhuman animal studies have robustly demonstrated that mothers process both
infant and other salient signals differently from nonmothers. Here, we
investigated how women with and without young infants respond to vocalisations
from infants and adults (both crying and neutral). We examined mothers with
infants ranging in age (1-14 months) to examine the effects of duration of
maternal experience. Using functional magnetic resonance imaging, we found that
mothers showed greater activity than nonmothers to vocalisations from adults or
infants in a range of cortical regions implicated in the processing of affective
auditory cues. This main effect of maternal status suggests a general difference
in vocalisation processing across infant and adult sounds. We found that a longer
duration of motherhood, and therefore more experience with an infant, was
associated with greater infant-specific activity in key parental brain regions,
including the orbitofrontal cortex and amygdala. We suggest that these
incremental differences in neural activity in the maternal brain reflect the
building of parental capacity over time. This is consistent with
conceptualizations of caregiving as a dynamic, learning process in humans.
PMID- 28496097
TI - Hepatitis B Virus e Antigen Activates the Suppressor of Cytokine Signaling 2 to
Repress Interferon Action.
AB - Hepatitis B virus (HBV) infection causes acute hepatitis B (AHB), chronic
hepatitis B (CHB), liver cirrhosis (LC), and eventually hepatocellular carcinoma
(HCC). The presence of hepatitis B e antigen (HBeAg) in the serum generally
indicates ongoing viral replication and disease progression. However, the
mechanism by which HBeAg regulates HBV infection remains unclear. Interferons
(IFNs) are pleiotropic cytokines that participate in host innate immunity. After
binding to receptors, IFNs activate the JAK/STAT pathway to stimulate expression
of IFN-stimulated genes (ISGs), leading to induction of antiviral responses.
Here, we revealed that HBeAg represses IFN/JAK/STAT signaling to facilitate HBV
replication. Initially, HBeAg stimulates the expression of suppressor of cytokine
signaling 2 (SOCS2). Subsequently, SOCS2 impairs IFN/JAK/STAT signaling through
reducing the stability of tyrosine kinase 2 (TYK2), downregulating the expression
of type I and III IFN receptors, attenuating the phosphorylation and nucleus
translocation of STAT1. Finally, SOCS2 inhibits the expression of ISGs, which
leads to the repression of IFN action and facilitation of viral replication.
These results demonstrate an important role of HBeAg in the regulation of IFN
action, and provide a possible molecular mechanism by which HBV resists the IFN
therapy and maintains persistent infection.
PMID- 28496098
TI - Combined treatment with Metformin and 2-deoxy glucose induces detachment of
viable MDA-MB-231 breast cancer cells in vitro.
AB - Triple naegative breast cancer has an increased rate of distant metastasis and
consequently poor prognosis. To metastasize, breast cancer cells must detach from
the main tumour mass and resist anoikis, a programmed cell death induced by lack
of cell-extracellular matrix communication. Although cancer cells must detach to
metastasize in vivo, the viability of floating cancer cells in vitro is rarely
investigated. Here we show that co-treatment of anoikis-resistant MDA-MB-231
cells with metformin and 2-deoxy-D-glucose (2-DG) increased the percentage of
floating cells, of which about 95% were viable. Floating cells resumed their
proliferation once they were reseeded in the pharmacological compound-free
medium. Similar effects on detachment were observed on anoikis-prone MCF-7 cells.
Co-treatment of MDA-MB-231 cells with metformin and 2-DG induced a strong
activation of AMP-activated protein kinase (AMPK), which was reduced by AMPK
inhibitor compound C that prevented detachment of MDA-MB-231 cells. However,
direct AMPK activators A-769662 and AICAR did not have any major effect on the
percentage of floating MDA-MB-231 cells, indicating that AMPK activation is
necessary but not sufficient for triggering detachment of cancer cells. Our
results demonstrate that separate analysis of floating and attached cancer cells
might be important for evaluation of anti-cancer agents.
PMID- 28496099
TI - Reentrant Resistive Behavior and Dimensional Crossover in Disordered
Superconducting TiN Films.
AB - A reentrant temperature dependence of the normal state resistance often referred
to as the N-shaped temperature dependence, is omnipresent in disordered
superconductors - ranging from high-temperature cuprates to ultrathin
superconducting films - that experience superconductor-to-insulator transition.
Yet, despite the ubiquity of this phenomenon its origin still remains a subject
of debate. Here we investigate strongly disordered superconducting TiN films and
demonstrate universality of the reentrant behavior. We offer a quantitative
description of the N-shaped resistance curve. We show that upon cooling down the
resistance first decreases linearly with temperature and then passes through the
minimum that marks the 3D-2D crossover in the system. In the 2D temperature range
the resistance first grows with decreasing temperature due to quantum
contributions and eventually drops to zero as the system falls into a
superconducting state. Our findings demonstrate the prime importance of disorder
in dimensional crossover effects.
PMID- 28496100
TI - Structure and function of a broad-specificity chitin deacetylase from Aspergillus
nidulans FGSC A4.
AB - Enzymatic conversion of chitin, a beta-1,4 linked polymer of N-acetylglucosamine,
is of major interest in areas varying from the biorefining of chitin-rich waste
streams to understanding how medically relevant fungi remodel their chitin
containing cell walls. Although numerous chitinolytic enzymes have been studied
in detail, relatively little is known about enzymes capable of deacetylating
chitin. We describe the structural and functional characterization of a 237
residue deacetylase (AnCDA) from Aspergillus nidulans FGSC A4. AnCDA acts on
chito-oligomers, crystalline chitin, chitosan, and acetylxylan, but not on
peptidoglycan. The K m and k cat of AnCDA for the first deacetylation of penta-N
acetyl-chitopentaose are 72 uM and 1.4 s-1, respectively. Combining mass
spectrometry and analyses of acetate release, it was shown that AnCDA catalyses
mono-deacetylation of (GlcNAc)2 and full deacetylation of (GlcNAc)3-6 in a non
processive manner. Deacetylation of the reducing end sugar was much slower than
deacetylation of the other sugars in chito-oligomers. These enzymatic
characteristics are discussed in the light of the crystal structure of AnCDA,
providing insight into how the chitin deacetylase may interact with its
substrates. Interestingly, AnCDA activity on crystalline chitin was enhanced by a
lytic polysaccharide monooxygenase that increases substrate accessibility by
oxidative cleavage of the chitin chains.
PMID- 28496101
TI - Stretchable, Twisted Conductive Microtubules for Wearable Computing, Robotics,
Electronics, and Healthcare.
AB - Stretchable and flexible multifunctional electronic components, including sensors
and actuators, have received increasing attention in robotics, electronics,
wearable, and healthcare applications. Despite advances, it has remained
challenging to design analogs of many electronic components to be highly
stretchable, to be efficient to fabricate, and to provide control over electronic
performance. Here, we describe highly elastic sensors and interconnects formed
from thin, twisted conductive microtubules. These devices consist of twisted
assemblies of thin, highly stretchable (>400%) elastomer tubules filled with
liquid conductor (eutectic gallium indium, EGaIn), and fabricated using a simple
roller coating process. As we demonstrate, these devices can operate as
multimodal sensors for strain, rotation, contact force, or contact location. We
also show that, through twisting, it is possible to control their mechanical
performance and electronic sensitivity. In extensive experiments, we have
evaluated the capabilities of these devices, and have prototyped an array of
applications in several domains of stretchable and wearable electronics. These
devices provide a novel, low cost solution for high performance stretchable
electronics with broad applications in industry, healthcare, and consumer
electronics, to emerging product categories of high potential economic and
societal significance.
PMID- 28496102
TI - Partial microduplication in the histone acetyltransferase complex member KANSL1
is associated with congenital heart defects in 22q11.2 microdeletion syndrome
patients.
AB - 22q11.2 microdeletion syndrome (22q11.2DS) is the most common microdeletion
disorder in humans, with an incidence of 1/4000 live births. It is caused by a
heterozygous deletion of 1.5-3 Mb on chromosome region 22q11.2. Patients with the
deletion present features that include neuropsychiatric problems, craniofacial
abnormalities and cardiovascular malformations. However, the phenotype is highly
variable and the factors related to the clinical heterogeneity are not fully
understood. About 65% of patients with 22q11.2DS have congenital heart defects
(CHD). The main goal of this study was to identify common CNVs in 22q11.2DS
patients that could be associated with the incomplete penetrance of CHD. Analysis
of genomic DNA from 253 patients with 22q11.2DS using array technology showed an
association between a microduplication located in region 17q21.31 and CHD (p
value = 0.023, OR = 2.75, 95% CI = 1.17-7.03). This region includes the first
three exons of KANSL1 gene. Bioinformatic analysis showed that KANSL1 and CRKL, a
gene in the commonly deleted region of 22q11.2DS, are part of the same regulatory
module in a miRNA-mRNA network. These results show that a KANSL1
microduplication, in combination with the 22q11.2 deletion, is associated with
increased risk of CHD in these patients, suggesting that KANSL1 plays a role as a
modifier gene in 22q11.2DS patients.
PMID- 28496103
TI - In situ printing of mesenchymal stromal cells, by laser-assisted bioprinting, for
in vivo bone regeneration applications.
AB - Bioprinting has emerged as a novel technological approach with the potential to
address unsolved questions in the field of tissue engineering. We have recently
shown that Laser Assisted Bioprinting (LAB), due to its unprecedented cell
printing resolution and precision, is an attractive tool for the in situ printing
of a bone substitute. Here, we show that LAB can be used for the in situ printing
of mesenchymal stromal cells, associated with collagen and nano-hydroxyapatite,
in order to favor bone regeneration, in a calvaria defect model in mice. Also, by
testing different cell printing geometries, we show that different cellular
arrangements impact on bone tissue regeneration. This work opens new avenues on
the development of novel strategies, using in situ bioprinting, for the building
of tissues, from the ground up.
PMID- 28496104
TI - Gender Differences in Bile Acids and Microbiota in Relationship with Gender
Dissimilarity in Steatosis Induced by Diet and FXR Inactivation.
AB - This study aims to uncover how specific bacteria and bile acids (BAs) contribute
to steatosis induced by diet and farnesoid X receptor (FXR) deficiency in both
genders. A control diet (CD) and Western diet (WD), which contains high fat and
carbohydrate, were used to feed wild type (WT) and FXR knockout (KO) mice
followed by phenotyping characterization as well as BA and microbiota profiling.
Our data revealed that male WD-fed FXR KO mice had the most severe steatosis and
highest hepatic and serum lipids as well as insulin resistance among the eight
studied groups. Gender differences in WD-induced steatosis, insulin sensitivity,
and predicted microbiota functions were all FXR-dependent. FXR deficiency
enriched Desulfovibrionaceae, Deferribacteraceae, and Helicobacteraceae, which
were accompanied by increased hepatic taurine-conjugated cholic acid and beta
muricholic acid as well as hepatic and serum lipids. Additionally, distinct
microbiota profiles were found in WD-fed WT mice harboring simple steatosis and
CD-fed FXR KO mice, in which the steatosis had a potential to develop into liver
cancer. Together, the presented data revealed FXR-dependent concomitant
relationships between gut microbiota, BAs, and metabolic diseases in both
genders. Gender differences in BAs and microbiota may account for gender
dissimilarity in metabolism and metabolic diseases.
PMID- 28496105
TI - Off-Stoichiometry Driven Carrier Density Variation at the Interface of
LaAlO3/SrTiO3.
AB - The interface between LaAlO3 (LAO) and SrTiO3 (STO) has attracted enormous
interests due to its rich physical phenomena, such as metallic nature, magnetism
and superconductivity. In this work, we report our experimental investigations on
the influence of the LAO stoichiometry to the metallic interface. Taking
advantage of the oxide molecular beam epitaxy (MBE) technique, a series of high
quality LAO films with different nominal La/Al ratios and LAO thicknesses were
grown on the TiO2-terminated STO substrates, where systematic variations of the
LAO lattice constant and transport property were observed. In particular, the
sheet density can be largely reduced by nearly an order of magnitude with merely
about 20% increase in the nominal La/Al ratio. Our finding provides an effective
method on tuning the electron density of the two-dimensional electron liquid
(2DEL) at the LAO/STO interface.
PMID- 28496106
TI - Neuregulin 1 improves complex 2-mediated mitochondrial respiration in skeletal
muscle of healthy and diabetic mice.
AB - It has been reported that neuregulin1 (NRG1) improves glucose tolerance in
healthy and diabetic rodents. In vitro studies also suggest that NRG1 regulates
myocyte oxidative capacity. To confirm this observation in vivo, we evaluated the
effect on mitochondrial function of an 8-week treatment with NRG1 in db/db
diabetic mice and C57BL/6JRJ healthy controls. NRG1 treatment improved complex 2
mediated mitochondrial respiration in the gastrocnemius of both control and
diabetic mice and increased mitochondrial complex 2 subunit content by 2-fold.
This effect was not associated with an increase in mitochondrial biogenesis
markers. Enhanced ERBB4 phosphorylation could mediate NRG1 effects on
mitochondrial function through signalling pathways, independently of ERK1/2, AKT
or AMPK.
PMID- 28496107
TI - CD163+CD204+ tumor-associated macrophages contribute to T cell regulation via
interleukin-10 and PD-L1 production in oral squamous cell carcinoma.
AB - Tumor-associated macrophages (TAMs) promote cancer cell proliferation, invasion,
and metastasis by producing various mediators. Although preclinical studies
demonstrated that TAMs preferentially express CD163 and CD204, the TAM subsets in
oral squamous cell carcinoma (OSCC) remain unknown. In this study, we examined
the expression and role of TAM subsets in OSCC. Forty-six patients with OSCC were
analyzed for expression of TAMs in biopsy samples by immunohistochemistry. We
examined TAM subsets and their production of immune suppressive molecules (IL-10
and PD-L1) in peripheral blood mononuclear cells from three OSCC patients by flow
cytometry. CD163 was detected around the tumor or connective tissue, while CD204
was detected in/around the tumors. Flow cytometric analysis revealed that
CD163+CD204+ TAMs strongly produced IL-10 and PD-L1 in comparison with
CD163+CD204- and CD163-CD204+ TAMs. Furthermore, the number of activated CD3+ T
cells after co-culture with CD163+CD204+ TAMs was significantly lower than that
after co-culture with other TAM subsets. In clinical findings, the number of
CD163+CD204+ TAMs was negatively correlated with that of CD25+ cells and 5-year
progression-free survival. These results suggest that CD163+CD204+ TAMs possibly
play a key role in the invasion and metastasis of OSCC by T-cell regulation via
IL-10 and PD-L1 production.
PMID- 28496108
TI - Alpha7 nicotinic acetylcholine receptor agonist promotes retinal ganglion cell
function via modulating GABAergic presynaptic activity in a chronic glaucomatous
model.
AB - Alpha-7 nicotinic acetylcholine receptor (alpha7-nAChR) agonists can prevent
glutamate-induced excitotoxicity in cultured retinal ganglion cells (RGCs).
However, the neuroprotective effects and the mechanism of action of PNU-282987,
an alpha7-nAChR agonist, in a chronic in vivo rat glaucoma model are poorly
understood. We found that elevated intraocular pressure (IOP) downregulated
retinal alpha7-nAChR expression. Electroretinography revealed that the amplitude
of the photopic negative response (PhNR) decreased in parallel with the loss of
RGCs caused by elevated IOP. PNU-282987 enhanced RGC viability and function and
decreased terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)
positive signals in RGCs. Patch-clamp recordings revealed differences in the
baseline frequencies and decay times of the miniature GABAergic inhibitory
postsynaptic currents (mIPSCs) of RGCs between control and glaucomatous retinal
slices. The results of western blotting and immunostaining showed that glutamic
acid decarboxylase 65/67 and GABA deficits persisted in glaucomatous retinas and
that these deficits were reversed by PNU-282987. Patch-clamp recordings also
showed that PNU-282987 significantly increased the frequency and amplitude of the
GABAergic mIPSCs of RGCs. The protective effects of PNU-292987 were blocked by
intravitreal administration of selective GABAA receptor antagonists. The
modulation of GABAergic synaptic transmission by PNU-282987 causes de-excitation
of ganglion cell circuits and suppresses excitotoxic processes.
PMID- 28496109
TI - The quantum Zeno and anti-Zeno effects with strong system-environment coupling.
AB - To date, studies of the quantum Zeno and anti-Zeno effects focus on quantum
systems that are weakly interacting with their environment. In this paper, we
investigate what happens to a quantum system under the action of repeated
measurements if the quantum system is strongly interacting with its environment.
We consider as the quantum system a single two-level system coupled strongly to a
collection of harmonic oscillators. A so-called polaron transformation is then
used to make the problem in the strong system-environment coupling regime
tractable. We find that the strong coupling case exhibits quantitative and
qualitative differences as compared with the weak coupling case. In particular,
the effective decay rate does not depend linearly on the spectral density of the
environment. This then means that, in the strong coupling regime that we
investigate, increasing the system-environment coupling strength can actually
decrease the effective decay rate. We also consider a collection of two-level
atoms coupled strongly with a common environment. In this case, we find that
there are further differences between the weak and strong coupling cases since
the two-level atoms can now indirectly interact with one another due to the
common environment.
PMID- 28496110
TI - The association between psychological stress and miscarriage: A systematic review
and meta-analysis.
AB - This systematic review and meta-analysis was designed to investigate whether
maternal psychological stress and recent life events are associated with an
increased risk of miscarriage. A literature search was conducted to identify
studies reporting miscarriage in women with and without history of exposure to
psychological stress (the only exposure considered). The search produced 1978
studies; 8 studies were suitable for analysis. A meta-analysis was performed
using a random-effects model with effect sizes weighted by the sampling variance.
The risk of miscarriage was significantly higher in women with a history of
exposure to psychological stress (OR 1.42, 95% CI 1.19-1.70). These findings
remained after controlling for study type (cohort and nested case-control study
OR 1.33 95% CI 1.14-1.54), exposure types (work stress OR 1.27, 95% CI 1.10
1.47), types of controls included (live birth OR 2.82 95% CI: 1.64-4.86). We
found no evidence that publication bias or study heterogeneity significantly
influenced the results. Our finding provides the most robust evidence to date,
that prior psychological stress is harmful to women in early pregnancy.
PMID- 28496111
TI - Indirect meta-analysis comparing clinical outcomes of total cervical disc
replacements with fusions for cervical degenerative disc disease.
AB - Anterior cervical discectomy and fusion (ACDF) and total cervical disc
replacement (TDR) are considered effective treatments for patients with cervical
degenerative disc disease (CDDD). An indirect meta-analysis including 19
randomized controlled trials (5343 patients) was conducted to compare the
clinical outcomes of ACDF with TDR. Primary outcomes including functional
indicators (NDI [neck disability index] score, neurological success and patient
satisfaction), secondary outcomes including surgical outcomes (operation time,
blood loss and length of stay) and secondary surgical procedures (secondary
surgery at an adjacent level, secondary surgery at the index level, secondary
surgery at both levels, removal, reoperation, revision and supplemental fixation)
were included in the study. TDR using the Bryan disc was associated with a
greater improvement in NDI score than ACDF (MD = -5.574, 95% CrIs [credible
intervals] -11.73--0.219). For neurological success, the Bryan (odds ratio [OR] =
0.559, 95% CrIs 0.323-0.955) and Prestige (OR = 0.474, 95% CrIs 0.319-0.700)
discs were superior to ACDF. However, no differences in the patient satisfaction
rate were shown between TDR and ACDF. For patients with CDDD, ACDF using
allograft and a plate is most effective for determining the surgical parameters.
Moreover, TDR using the ProDisc-C, Mobi-C, Prestige and Bryan discs are good
choices for improving functional outcomes and reducing secondary surgeries.
PMID- 28496112
TI - "TORNADO" - Theranostic One-Step RNA Detector; microfluidic disc for the direct
detection of microRNA-134 in plasma and cerebrospinal fluid.
AB - Diagnosis of seizure disorders such as epilepsy currently relies on clinical
examination and electroencephalogram recordings and is associated with
substantial mis-diagnosis. The miRNA, miR-134 (MIR134 in humans), has been found
to be elevated in brain tissue after experimental status epilepticus and in human
epilepsy cells and their detection in biofluids may serve as unique biomarkers.
miRNAs from unprocessed human plasma and human cerebrospinal fluid samples were
used in a novel electrochemical detection based on electrocatalytic platinum
nanoparticles inside a centrifugal microfluidic device where the sandwich assay
is formed using an event triggered release system, suitable for the rapid point
of-care detection of low abundance biomarkers of disease. The device has the
advantage of controlling the rotation speed of the centrifugal device to pump
nanoliter volumes of fluid at a set time and manipulate the transfer of liquids
within the device. The centrifugal platform improves reaction rates and yields by
proposing efficient mixing strategies to overcome diffusion-limited processes and
improve mass transport rates, resulting in reduced hybridization times with a
limit of detection of 1 pM target concentration. Plasma and cerebrospinal fluid
samples (unprocessed) from patients with epilepsy or who experienced status
epilepticus were tested and the catalytic response obtained was in range of the
calibration plot. This study demonstrates a rapid and simple detection for
epilepsy biomarkers in biofluid.
PMID- 28496113
TI - The Beneficial Role of Mobility for the Emergence of Innovation.
AB - Innovation is a key ingredient for the evolution of several systems, including
social and biological ones. Focused investigations and lateral thinking may lead
to innovation, as well as serendipity and other random discovery processes. Some
individuals are talented at proposing innovation (say innovators), while others
at deeply exploring proposed novelties, at getting further insights on a theory,
or at developing products, services, and so on (say developers). This separation
in terms of innovators and developers raises an issue of paramount importance:
under which conditions a system is able to maintain innovators? According to a
simple model, this work investigates the evolutionary dynamics that characterize
the emergence of innovation. In particular, we consider a population of
innovators and developers, in which agents form small groups whose composition is
crucial for their payoff. The latter depends on the heterogeneity of the formed
groups, on the amount of innovators they include, and on an award-factor that
represents the policy of the system for promoting innovation. Under the
hypothesis that a "mobility" effect may support the emergence of innovation, we
compare the equilibria reached by our population in different cases. Results
confirm the beneficial role of "mobility", and the emergence of further
interesting phenomena.
PMID- 28496115
TI - Erratum: A two-qubit photonic quantum processor and its application to solving
systems of linear equations.
PMID- 28496114
TI - New quaternary half-metallic ferromagnets with large Curie temperatures.
AB - New magnetic materials with high Curie temperatures for spintronic applications
are perpetually sought for. In this paper, we present an ab initio study of the
structural, electronic and magnetic properties of Quaternary Heusler compounds
CoX'Y'Si where X' is a transition metal with 4d electrons and Y' is either Fe or
Mn. We find five new half-metallic ferromagnets with spin polarisation nearly
100% with very high Curie temperatures. The variation of Curie temperatures as a
function of valence electrons can be understood from the calculated inter-atomic
exchange interaction parameters. We also identify a few other compounds, which
could be potential half-metals with suitable application of pressure or with
controlled doping. Our results reveal that the half-metallicity in these
compounds is intricately related to the arrangements of the magnetic atoms in the
Heusler lattice and hence, the interatomic exchange interactions between the
moments. The trends in the atomic arrangements, total and local magnetic moments,
interatomic magnetic exchange interactions and Curie temperatures are discussed
with fundamental insights.
PMID- 28496116
TI - Antinociceptive effects of caloric restriction on post-incisional pain in
nonobese rats.
AB - Caloric restriction (CR) increases lifespan, retards physiological signs of
aging, and delays a variety of diseases. Reduction of inflammatory response was
proposed as one of the molecular mechanisms for how CR exerts beneficial effects.
The present study investigated the effects of CR on postoperative pain in rats.
Adult nonobese rats were divided into two dietary groups, an ad libitum fed group
(AL) and a caloric restriction group (CR) that was provided with 60% of the food
intake of AL rats. After 6 weeks, the effects of CR on pain behaviors and
inflammation induced by plantar incision were examined. CR rats displayed
significantly reduced nonevoked pain, mechanical allodynia and thermal
hyperalgesia induced by incision, and showed decreased levels of pro-inflammatory
cytokines in serum, peri-incisional skin tissue and ipsilateral spinal cord
dorsal horn at 6 h and 24 h after incision. The analgesic efficiency of parecoxib
and morphine, two agents widely used for the management of postoperative pain
clinically, was reinforced by CR. Together, CR generates antinociceptive effects
on postoperative incisional pain in rats, perhaps providing some improvement of
QOL in patients with postoperative pain, and the beneficial effects may be
attributable to the inhibition of excessive inflammation induced by surgical
injury.
PMID- 28496117
TI - The Guanacaste Volcanic Arc Sliver of Northwestern Costa Rica.
AB - Recent studies have shown that the Nicoya Peninsula of northwestern Costa Rica is
moving northwestward ~11 mm a-1 as part of a tectonic sliver. Toward the
northwest in El Salvador the northern sliver boundary is marked by a dextral
strike-slip fault system active since Late Pleistocene time. To the southeast
there is no consensus on what constitutes the northern boundary of the sliver,
although a system of active crustal faults has been described in central Costa
Rica. Here we propose that the Haciendas-Chiripa fault system serves as the
northeastern boundary for the sliver and that the sliver includes most of the
Guanacaste volcanic arc, herein the Guanacaste Volcanic Arc Sliver. In this paper
we provide constraints on the geometry and kinematics of the boundary of the
Guanacaste Volcanic Arc Sliver that are timely and essential to any models aimed
at resolving the driving mechanism for sliver motion. Our results are also
critical for assessing geological hazards in northwestern Costa Rica.
PMID- 28496118
TI - Quantum interference and heteroaromaticity of para- and meta-linked bridged
biphenyl units in single molecular conductance measurements.
AB - Is there a correlation between the (hetero)aromaticity of the core of a molecule
and its conductance in a single molecular junction? To address this question,
which is of fundamental interest in molecular electronics, oligo(arylene
ethynylene) (OAE) molecular wires have been synthesized with core units
comprising dibenzothiophene, carbazole, dibenzofuran and fluorene. The biphenyl
core has been studied for comparison. Two isomeric series have been obtained with
4-ethynylpyridine units linked to the core either at para-para positions (para
series 1-5) or meta-meta positions (meta series 6-10). A combined experimental
and computational study, using mechanically controlled break junction
measurements and density functional theory calculations, demonstrates
consistently higher conductance in the para series compared to the meta series:
this is in agreement with increased conjugation of the pi-system in the para
series. Within the para series conductance increases in the order of decreasing
heteroaromaticity (dibenzothiophene < carbazole < dibenzofuran). However, the
sequence is very different in the meta series, where dibenzothiophene ~
dibenzofuran < carbazole. Excellent agreement between theoretical and
experimental conductance values is obtained. Our study establishes that both
quantum interference and heteroaromaticity in the molecular core units play
important and inter-related roles in determining the conductance of single
molecular junctions.
PMID- 28496119
TI - Clinical experience with the artificial bone graft substitute Calcibon used
following curettage of benign and low-grade malignant bone tumors.
AB - Artificial bone graft substitutes, such as Calcibon, are becoming increasingly
interesting as they do not cause donor site morbidity which is an advantage
compared to autologous bone grafts. The aim of this study was to evaluate the
efficacy and potential complications associated with the use of Calcibon. Twenty
seven patients with benign and low-grade malignant bone tumors were treated with
curettage and refilling of the bony cavity. Based on the radiological
classification system of Neer, these lesions only comprised Grade I lesions,
describing cysts that only require curettage and filling, but no additional
treatment. At a mean follow up of six months we observed radiological
consolidation without resorption of the bone graft substitute. These observations
were also made at a mean follow-up of 13 and 32 months, respectively. According
to the classification system of Goslings and Gouma we observed six surgical
complications. Summing up, Calcibon seems to be a reliable bone graft substitute
with low complication rates. However, delayed resorption should be expected.
Calcibon seems to be an alternative to autologous bone grafts or allografts in
adequate indications.
PMID- 28496120
TI - Band Gap Engineering of Multi-Junction Solar Cells: Effects of Series Resistances
and Solar Concentration.
AB - Multi-junction (MJ) solar cells are one of the most promising technologies
achieving high sunlight to electricity conversion efficiency. Resistive losses
constitute one of the main underlying mechanisms limiting their efficiency under
high illumination. In this paper, we study, by numerical modeling, the extent to
which a fine-tuning of the different electronic gaps involved in MJ stacks may
mitigate the detrimental effects of series resistance losses for concentration
dependent and independent series resistances. Our results demonstrate that
appropriate bandgap engineering may lead to significantly higher conversion
efficiency at illumination levels above ~1000 suns and series resistance values
typically exceeding 0.02 Omega cm2, due to lower operating current and, in turn,
series resistance losses. The implications for future generations of solar cells
aiming at an improved conversion of the solar spectrum are also addressed.
PMID- 28496121
TI - ZnO@C (core@shell) microspheres derived from spent coffee grounds as applicable
non-precious electrode material for DMFCs.
AB - Although numerous reports have introduced non precious electrocatalysts for
methanol oxidation, most of those studies did not consider the corresponding high
onset potential which restricts utilization in real fuel cells. In this study, an
-90 mV [vs. Ag/AgCl] onset potential non-precious electrocatalyst is introduced
as an applicable anode material for the direct methanol fuel cells. Moreover, the
proposed material was prepared from a cheap and abundantly existing resource; the
spent coffee grounds. Typically, the spent coffee grounds were facilely converted
to core@shell (ZnO@C) microspheres through a two-step approach, involving
chemical activation and a subsequent calcination at temperature of 700 degrees
C. Activation of the carbon derived from the spent coffee grounds was performed
with ZnCl2 which acts as pore-forming agent as well as a precursor for the ZnO.
The structure and morphology were characterized by (XRD), (SEM), and (TEM)
analyses while the electrochemical characterizations was evaluated by cyclic
voltammetry (CV) technique. Besides the comparatively very low onset potential,
the introduced microspheres exhibited relatively high current density; 17 mA/cm2.
Overall, based on the advantages of the green source of carbon and the good
electrocatalytic activity, the spent coffee grounds-derived carbon can be
considered a promise anode material for the DMFCs.
PMID- 28496124
TI - Intelligibility of locally time-reversed speech: A multilingual comparison.
AB - A set of experiments was performed to make a cross-language comparison of
intelligibility of locally time-reversed speech, employing a total of 117 native
listeners of English, German, Japanese, and Mandarin Chinese. The experiments
enabled to examine whether the languages of three types of timing-stress-,
syllable-, and mora-timed languages-exhibit different trends in intelligibility,
depending on the duration of the segments that were temporally reversed. The
results showed a strikingly similar trend across languages, especially when the
time axis of segment duration was normalised with respect to the deviation of a
talker's speech rate from the average in each language. This similarity is
somewhat surprising given the systematic differences in vocalic proportions
characterising the languages studied which had been shown in previous research
and were largely replicated with the present speech material. These findings
suggest that a universal temporal window shorter than 20-40 ms plays a crucial
role in perceiving locally time-reversed speech by working as a buffer in which
temporal reorganisation can take place with regard to lexical and semantic
processing.
PMID- 28496122
TI - Structural insights into a 20.8-kDa tegumental-allergen-like (TAL) protein from
Clonorchis sinensis.
AB - Survival of Clonorchis sinensis, a cause of human clonorchiasis, requires
tegument proteins, which are localized to the tegumental outer surface membrane.
These proteins play an important role in a host response and parasite survival.
Thus, these proteins are interesting molecular targets for vaccine and drug
development. Here, we have determined two crystal structures of the calmodulin
like domain (amino acid [aa] positions 1-81) and dynein light chain (DLC)-like
domain (aa 83-177) of a 20.8-kDa tegumental-allergen-like protein from Clonorchis
sinensis (CsTAL3). The calmodulin like domain has two Ca2+-binding sites (named
CB1 and CB2), but Ca2+ binds to only one site, CB1. The DLC-like domain has a
dimeric conformation; the interface is formed mainly by hydrogen bonds between
the main chain atoms. In addition, we have determined full-length structure of
CsTAL3 in solution and showed the conformational change of CsTAL3 induced by Ca2+
ion binding using small-angle X-ray scattering analysis and molecular dynamics
simulations. The Ca2+-bound form has a more extended conformation than the Ca2+
free from does. These structural and biochemical analyses will advance the
understanding of the biology of this liver fluke and may contribute to our
understanding of the molecular mechanism of calcium-responsive and tegumental
allergen-like proteins.
PMID- 28496123
TI - Systematic evaluation for effects of urine pH on calcium oxalate crystallization,
crystal-cell adhesion and internalization into renal tubular cells.
AB - Urine pH has been thought to be an important factor that can modulate kidney
stone formation. Nevertheless, there was no systematic evaluation of such pH
effect. Our present study thus addressed effects of differential urine pH (4.0
8.0) on calcium oxalate (CaOx) crystallization, crystal-cell adhesion, crystal
internalization into renal tubular cells, and binding of apical membrane proteins
to the crystals. Microscopic examination revealed that CaOx monohydrate (COM),
the pathogenic form, was crystallized with greatest size, number and total mass
at pH 4.0 and least crystallized at pH 8.0, whereas COD was crystallized with the
vice versa order. Fourier-transform infrared (FT-IR) spectroscopy confirmed such
morphological study. Crystal-cell adhesion assay showed the greatest degree of
crystal-cell adhesion at the most acidic pH and least at the most basic pH.
Crystal internalization assay using fluorescein isothiocyanate (FITC)-labelled
crystals and flow cytometry demonstrated that crystal internalization into renal
tubular cells was maximal at the neutral pH (7.0). Finally, there were no
significant differences in binding capacity of the crystals to apical membrane
proteins at different pH. We concluded that the acidic urine pH may promote CaOx
kidney stone formation, whereas the basic urine pH (i.e. by alkalinization) may
help to prevent CaOx kidney stone disease.
PMID- 28496126
TI - Fabrication-constrained nanophotonic inverse design.
AB - A major difficulty in applying computational design methods to nanophotonic
devices is ensuring that the resulting designs are fabricable. Here, we describe
a general inverse design algorithm for nanophotonic devices that directly
incorporates fabrication constraints. To demonstrate the capabilities of our
method, we designed a spatial-mode demultiplexer, wavelength demultiplexer, and
directional coupler. We also designed and experimentally demonstrated a compact,
broadband 1 * 3 power splitter on a silicon photonics platform. The splitter has
a footprint of only 3.8 * 2.5 MUm, and is well within the design rules of a
typical silicon photonics process, with a minimum radius of curvature of 100 nm.
Averaged over the designed wavelength range of 1400-1700 nm, our splitter has a
measured insertion loss of 0.642 +/- 0.057 dB and power uniformity of 0.641 +/-
0.054 dB.
PMID- 28496125
TI - Enhancing Specific Disruption of Intracellular Protein Complexes by Hydrocarbon
Stapled Peptides Using Lipid Based Delivery.
AB - Linear peptides can mimic and disrupt protein-protein interactions involved in
critical cell signaling pathways. Such peptides however are usually protease
sensitive and unable to engage with intracellular targets due to lack of membrane
permeability. Peptide stapling has been proposed to circumvent these limitations
but recent data has suggested that this method does not universally solve the
problem of cell entry and can lead to molecules with off target cell lytic
properties. To address these issues a library of stapled peptides was synthesized
and screened to identify compounds that bound Mdm2 and activated cellular p53. A
lead peptide was identified that activated intracellular p53 with negligible
nonspecific cytotoxicity, however it still bound serum avidly and only showed a
marginal improvement in cellular potency. These hurdles were overcome by
successfully identifying a pyridinium-based cationic lipid formulation, which
significantly improved the activity of the stapled peptide in a p53 reporter cell
line, principally through increased vesicular escape. These studies underscore
that stapled peptides, which are cell permeable and target specific, can be
identified with rigorous experimental design and that these properties can be
improved through use with lipid based formulations. This work should facilitate
the clinical translation of stapled peptides.
PMID- 28496127
TI - Controlling magnetic transition of monovacancy graphene by shear distortion.
AB - The effect of shear distortion on the vacancy induced magnetism in graphene is
investigated using extensive first-principles calculations. It is found that
shear distortion can lead to magnetic transition between two states with high and
low magnetic moments. Such a transition is reversible and results from the
breaking of the in-plane symmetry of the local atoms, which reverses spin
polarization of the pi bands of the vacancy states near the Fermi level and leads
to the change of magnetic transition by 1 uB. This finding opens the possibility
for nanomechanical control of graphene magnetism and has potential applications
in spintronics and magnetic sensing.
PMID- 28496129
TI - Acoustoelectric Current in Graphene Nanoribbons.
AB - Surface acoustic waves (SAWs) propagating on piezoelectric substrates offer a
convenient, contactless approach to probing the electronic properties of low
dimensional charge carrier systems such as graphene nanoribbons (GNRs). SAWs can
also be used to transport and manipulate charge for applications such as
metrology and quantum information. In this work, we investigate the
acoustoelectric effect in GNRs, and show that an acoustoelectric current can be
generated in GNRs with physical widths as small as 200 nm at room temperature.
The positive current in the direction of the SAWs, which corresponds to the
transportation of holes, exhibits a linear dependence on SAW intensity and
frequency. This is consistent with the description of the interaction between the
charge carriers in the GNRs and the piezoelectric fields associated with the SAWs
being described by a relatively simple classical relaxation model. Somewhat
counter-intuitively, as the GNR width is decreased, the measured acoustoelectric
current increases. This is thought to be caused by an increase of the carrier
mobility due to increased doping arising from damage to the GNR edges.
PMID- 28496128
TI - A Systems Genetics Approach Identified GPD1L and its Molecular Mechanism for
Obesity in Human Adipose Tissue.
AB - To explore novel molecular mechanisms underlying obesity, we applied a systems
genetics framework to integrate risk genetic loci from the largest body mass
index (BMI) genome-wide association studies (GWAS) meta-analysis with mRNA and
microRNA profiling in adipose tissue from 200 subjects. One module was identified
to be most significantly associated with obesity and other metabolic traits. We
identified eight hub genes which likely play important roles in obesity
metabolism and identified microRNAs that significantly negatively correlated with
hub genes. This module was preserved in other three test gene expression
datasets, and all hub genes were consistently downregulated in obese subjects
through the meta-analysis. Gene GPD1L had the highest connectivity and was
identified a key causal regulator in the module. Gene GPD1L was significantly
negatively correlated with the expression of miR-210, which was experimentally
validated that miR-210 regulated GPD1L protein level through direct interaction
with its mRNA three prime untranslated region (3'-UTR). GPD1L was found to be
upregulated during weight loss and weight maintenance induced by low calorie diet
(LCD), while downregulated during weight gain induced by high-fat diet (HFD). The
results indicated that increased GPD1L in adipose tissue may have a significant
therapeutic potential in reducing obesity and insulin resistance.
PMID- 28496130
TI - An Aqueous-Based Approach for Fabrication of PVDF/MWCNT Porous Composites.
AB - In this paper, we demonstrate the fabrication of conductive porous polymers based
on foaming of an aqueous dispersion of polymeric particles and multi-walled
carbon nanotubes (CNT). By tuning the surface energy of the constituents, we
direct their preferential adsorption at the air-liquid (bubble) interface or
within the liquid film between the bubbles. Sintering this bi-constituent foam
yields solid closed-cell porous structure which can be electrically conductive if
CNT are able to form a conductive path. We measure transport (electrical and
thermal), mechanical, and morphological properties of such porous structures as a
function of CNT loading and the method used for their surface functionalization.
For a fixed polymer volume fraction, we demonstrate the limit in which increasing
CNT results in decreasing the mechanical strength of the sample due to lack of
adequate polymer-CNT bond. Such lightweight conductive porous composites are
considered in applications including EMI shielding, electrostatic discharge
protection, and electrets.
PMID- 28496131
TI - Leveraging multiple genomic data to prioritize disease-causing indels from exome
sequencing data.
AB - The emergence of exome sequencing in recent years has enabled rapid and cost
effective detection of genetic variants in coding regions and offers a great
opportunity to combine sequencing experiments with subsequent computational
analysis for dissecting genetic basis of human inherited diseases. However, this
strategy, though successful in practice, still faces such challenges as limited
sample size and substantial number or diversity of candidate variants. To
overcome these obstacles, researchers have been concentrated in the development
of advanced computational methods and have recently achieved great progress for
analysing single nucleotide variant. Nevertheless, it still remains unclear on
how to analyse indels, another type of genetic variant that accounts for
substantial proportion of known disease-causing variants. In this paper, we
proposed an integrative method to effectively identify disease-causing indels
from exome sequencing data. Specifically, we put forward a statistical method to
combine five functional prediction scores, four genic association scores and a
genic intolerance score to produce an integrated p-value, which could then be
used for prioritizing candidate indels. We performed extensive simulation studies
and demonstrated that our method achieved high accuracy in uncovering disease
causing indels. Our software is available at
http://bioinfo.au.tsinghua.edu.cn/jianglab/IndelPrioritizer/.
PMID- 28496132
TI - Serum sonic hedgehog (SHH) and interleukin-(IL-6) as dual prognostic biomarkers
in progressive metastatic breast cancer.
AB - Serum from one hundred and ten breast cancer patients and thirty healthy female
volunteers, were prospectively collected and evaluated for serum levels of Shh
and IL-6 using human Shh and IL-6 specific enzyme-linked immunoassays. All
patients were regularly monitored for event free survival (EFS) and overall
survival (OS). Overall outcome analysis was based on serum Shh and IL-6 levels.
In patients with progressive metastatic BC, both serum Shh and IL-6
concentrations were elevated in 44% (29 of 65) and 63% (41 of 65) of patients,
respectively, at a statistically significant level [Shh (p = 0.0001) and IL-6 (p
= 0.0001)] compared to the low levels in healthy volunteers. Serum levels tended
to increase with metastatic progression and lymph node positivity. High serum Shh
and IL-6 levels were associated with poor EFS and OS opposite to the negative or
lower levels in serum Shh and IL-6. The elevated levels of both serum Shh and IL
6 were mainly observed in BC patients who had a significantly higher risk of
early recurrence and bone metastasis, and associated with a worse survival for
patients with progressive metastatic BC. Further studies are warranted for
validating these biomarkers as prognostic tools in a larger patient cohort and in
a longer follow-up study.
PMID- 28496133
TI - Folate Metabolism Regulates Oligodendrocyte Survival and Differentiation by
Modulating AMPKalpha Activity.
AB - Folate, an essential micronutrient, is a critical cofactor in one-carbon
metabolism for many cellular pathways including DNA synthesis, metabolism and
maintenance. Folate deficiency has been associated with an increased risk of
neurological disease, cancer and cognitive dysfunction. Dihydrofolate reductase
(DHFR) is a key enzyme to regulate folate metabolism, however folate/DHFR
activity in oligodendrocyte development has not been fully understood. Here we
show that folate enhances oligodendrocyte maturation both in vitro and in vivo,
which is accompanied with upregulation of oligodendrocyte-specific DHFR
expression. On the other hand, pharmacological inhibition of DHFR by methotrexate
(MTX) causes severe defects in oligodendrocyte survival and differentiation,
which could be reversed by folate intake. We further demonstrate that folate
activates a metabolic regulator AMPKalpha to promote oligodendrocyte survival and
differentiation. Moreover, activation of AMPKalpha partially rescues
oligodendrocyte defects caused by DHFR-inhibition both in vitro and in vivo.
Taken together, these findings identify a previously uncharacterized role of
folate/DHFR/AMPKalpha axis in regulating oligodendrocyte survival and myelination
during CNS development.
PMID- 28496134
TI - Inkjet printing of NiO films and integration as hole transporting layers in
polymer solar cells.
AB - Stability concerns of organic solar cell devices have led to the development of
alternative hole transporting layers such as NiO which lead to superior device
life times over conventional Poly(3,4-ethylenedioxythiophene) Polystyrene
sulfonate (PEDOT:PSS) buffered solar cells. From the printability of such
devices, it is imperative to be able to print NiO layers in the organic solar
cell devices with normal architecture which has so far remained unreported. In
this manuscript, we report on the successful ink-jet printing of very thin NiO
thin films with controlled thickness and morphology and their integration in
organic solar cell devices. The parameters that were found to strongly affect the
formation of a thin yet continuous NiO film were substrate surface treatment,
drop spacing, and substrate temperature during printing. The effect of these
parameters was investigated through detailed morphological characterization using
optical and atomic force microscopy and the results suggested that one can
achieve a transmittance of ~89% for a ~18 nm thin NiO film with uniform structure
and morphology, fabricated using a drop spacing of 50 MUm and a heat treatment
temperature of 400 degrees C. The devices fabricated with printed NiO hole
transporting layers exhibit power conversion efficiencies comparable to the
devices with spin coated NiO films.
PMID- 28496135
TI - Isolated Bacillus subtilis strain 330-2 and its antagonistic genes identified by
the removing PCR.
AB - Plant growth-promoting bacteria (PGPB) may trigger tolerance against
biotic/abiotic stresses and growth enhancement in plants. In this study, an
endophytic bacterial strain from rapeseed was isolated to assess its role in
enhancing plant growth and tolerance to abiotic stresses, as well as banded leaf
and sheath blight disease in maize. Based on 16S rDNA and BIOLOG test analysis,
the 330-2 strain was identified as Bacillus subtilis. The strain produced indole
3-acetic acid, siderophores, lytic enzymes and solubilized different sources of
organic/inorganic phosphates and zinc. Furthermore, the strain strongly
suppressed the in vitro growth of Rhizoctonia solani AG1-IA, Botrytis cinerea,
Fusarium oxysporum, Alternaria alternata, Cochliobolus heterostrophus, and
Nigrospora oryzae. The strain also significantly increased the seedling growth
(ranging 14-37%) of rice and maize. Removing PCR analysis indicated that 114
genes were differentially expressed, among which 10%, 32% and 10% were involved
in antibiotic production (e.g., srfAA, bae, fen, mln, and dfnI), metabolism
(e.g., gltA, pabA, and ggt) and transportation of nutrients (e.g., fhu, glpT, and
gltT), respectively. In summary, these results clearly indicate the effectiveness
and mechanisms of B. subtilis strain 330-2 in enhancing plant growth, as well as
tolerance to biotic/abiotic stresses, which suggests that the strain has great
potential for commercialization as a vital biological control agent.
PMID- 28496136
TI - The S. aureus 4-oxalocrotonate tautomerase SAR1376 enhances immune responses when
fused to several antigens.
AB - A persistent goal of vaccine development is the enhancement of the immunogenicity
of antigens while maintaining safety. One strategy involves alteration of the
presentation of the antigen by combining antigens with a multimeric scaffold.
Multi-antigen vaccines are under development, and there are presently far more
candidate antigens than antigen scaffolding strategies. This is potentially
problematic, since prior immunity to a scaffold may inhibit immune responses to
the antigen-scaffold combination. In this study, a series of domains from S.
aureus which have been shown to crystallise into multimeric structures have been
examined for their scaffolding potential. Of these domains, SAR1376, a 62 amino
acid member of the 4-oxalocrotonate tautomerase (4-OT) family, was pro
immunogenic in mice when fused to a range of pathogen antigens from both S.
aureus and P. falciparum, and delivered by either DNA vaccination, viral vector
vaccines or as protein-in-adjuvant formulations. The adjuvant effect did not
depend on enzymatic activity, but was abrogated by mutations disrupting the
hexameric structure of the protein. We therefore propose that SAR1376, and
perhaps other members of the 4-OT protein family, represent very small domains
which can be fused to a wide range of antigens, enhancing immune responses
against them.
PMID- 28496137
TI - Tumor suppressor menin is required for subunit-specific nAChR alpha5
transcription and nAChR-dependent presynaptic facilitation in cultured mouse
hippocampal neurons.
AB - In the central nervous system (CNS), cholinergic transmission induces synaptic
plasticity that is required for learning and memory. However, our understanding
of the development and maintenance of cholinergic circuits is limited, as the
factors regulating the expression and clustering of neuronal nicotinic
acetylcholine receptors (nAChRs) remain poorly defined. Recent studies from our
group have implicated calpain-dependent proteolytic fragments of menin, the
product of the MEN1 tumor suppressor gene, in coordinating the transcription and
synaptic clustering of nAChRs in invertebrate central neurons. Here, we sought to
determine whether an analogous cholinergic mechanism underlies menin's
synaptogenic function in the vertebrate CNS. Our data from mouse primary
hippocampal cultures demonstrate that menin and its calpain-dependent C-terminal
fragment (C-menin) regulate the subunit-specific transcription and synaptic
clustering of neuronal nAChRs, respectively. MEN1 knockdown decreased nAChR
alpha5 subunit expression, the clustering of alpha7 subunit-containing nAChRs at
glutamatergic presynaptic terminals, and nicotine-induced presynaptic
facilitation. Moreover, the number and function of glutamatergic synapses was
unaffected by MEN1 knockdown, indicating that the synaptogenic actions of menin
are specific to cholinergic regulation. Taken together, our results suggest that
the influence of menin on synapse formation and synaptic plasticity occur via
modulation of nAChR channel subunit composition and functional clustering.
PMID- 28496138
TI - Severe bilateral ischemic-reperfusion renal injury: hyperacute and acute changes
in apparent diffusion coefficient, T1, and T2 mapping with immunohistochemical
correlations.
AB - The aim of this study was to investigate the hyperacute and acute changes in
apparent diffusion coefficient (ADC), T1, and T2 mapping in rat kidneys after
severe bilateral renal ischemic-reperfusion injury (IRI). After baseline MRI, 24
Spraque-Dawley rats with renal IRI were divided equally as group 1 (post-IRI MRI
at 6 hours, days 1, 3, and 7) and groups 2, 3, and 4 (post-IRI MRI at 6 hours; 6
hours and day 1; 6 hours, days 1 and 3, respectively), while six other rats
without IRI (group 5) were used as sham control. ADC, T1, and T2 values of the
cortex and outer and inner stripes of outer medulla (OSOM and ISOM), and
immunohistochemical studies assessing monocyte chemoattractant protein-1 (MCP-1),
CD68+ cells, tubular cast formation, and collagen deposition in three zones at
different time points were evaluated. Significantly reduced ADCs in OSOM and ISOM
are noninvasive biomarkers denoting hyperacute damages after IRI. Linear
regression analysis revealed a significant inverse correlation between 6
hour/baseline ADC ratios and MCP-1 staining (P < 0.001, r2 = 0.738). ADC, T1, and
T2 values are useful for assessing variable IRI changes in different layers
depending on underlying microstructural and histopathological changes at
different time points.
PMID- 28496139
TI - Operational lifetimes of organic light-emitting diodes dominated by Forster
resonance energy transfer.
AB - Organic light-emitting diodes are a key technology for next-generation
information displays because of their low power consumption and potentially long
operational lifetimes. Although devices with internal quantum efficiencies of
approximately 100% have been achieved using phosphorescent or thermally activated
delayed fluorescent emitters, a systematic understanding of materials suitable
for operationally stable devices is lacking. Here we demonstrate that the
operational stability of phosphorescent devices is nearly proportional to the
Forster resonance energy transfer rate from the host to the emitter when
thermally activated delayed fluorescence molecules are used as the hosts. We find
that a small molecular size is a requirement for thermally activated delayed
fluorescence molecules employed as phosphorescent hosts; in contrast, an
extremely small energy gap between the singlet and triplet excited states, which
is essential for an efficient thermally activated delayed fluorescent emitter, is
unnecessary in the phosphorescent host.
PMID- 28496140
TI - The Impact of a Severe Drought on Dust Lifting in California's Owens Lake Area.
AB - Mineral dust aerosols are responsible for some of the largest sources of
uncertainties in our current understanding of climate change. Here we show that a
severe drought is having a significant impact in one of largest sources of
mineral dust aerosols of the U.S., the Owens Lake area in California's southwest.
Measurements of aerosol concentration (PM2.5 particle matter) in the Owens Lake
salty playa show that the annual mean concentration of PM2.5 aerosol has been
increasing steadily since the beginning of the current drought, with periods of
high aerosol concentration increasing from 4 months in 2013 to 9 months in 2015.
Interestingly, the PM2.5 aerosol concentration usually increases abruptly from
less than ~0.05 mg/m3 to ~0.25 mg/m3. This occurs when saltation events break
salt crusts produced by the efflorescence of brine in the salty playa. The brine
is produced by either rainfall or runoff water. Based on this observation, we
hypothesize that there is an upper limit of ~0.25 mg/m3 in the annual mean PM2.5
aerosols concentration in the Owens Lake basin that might limit the impact of
mineral dust aerosols on climate. Indeed, the upper annual limit of ~0.25 mg/m3
has been nearly reached during the current drought.
PMID- 28496141
TI - A randomized comparison of the prone ventilation endotracheal tube versus the
traditional endotracheal tube in adult patients undergoing prone position
surgery.
AB - Endotracheal tube displacement or dislocation is a severe complication that can
occur in patients who require prone position ventilation. We hypothesized the
prone position tube (PPT) would reduce the incidence of displacement of an
endotracheal tube in an adult prone operation compared to a traditional tube
(TT). A total of 80 adult patients undergoing neurosurgery or spine surgery were
recruited. Sixty patients with prone position ventilation were randomly divided
into the traditional routine endotracheal tube group (Group TT, n = 30) and the
prone position ventilation endotracheal tube group (Group PPT, n = 30). The
primary outcome measures were the incidence of the endotracheal tube displacement
during surgery, and the secondary outcomes were symptoms of sore throat,
dysphagia and dysphonia during follow-up in the post-anesthesia care unit (PACU).
The incidence of tube displacement was significantly lower in the PPT group (0
[0%] of 30 patients) compared to the TT group (22 [73.3%] of 30 patients; odds
ratio [OR] 0.73, 95% CI 0.591-0.910; P = 0.005). There was no statistical
difference in sore throat, dysphagia and vocal function between the two groups (P
> 0.05) during follow-up. Compared to the traditional tube, the improved prone
positon tube reduced the incidence of displacement of the endotracheal tube. This
study was registered with ClinicalTrials.gov on April 29, 2015 (No. NCT02449356).
PMID- 28496142
TI - Src-homology protein tyrosine phosphatase-1 agonist, SC-43, reduces liver
fibrosis.
AB - This study aimed to investigate the role of src-homology protein tyrosine
phosphatase-1 (SHP-1)-signal transducer and activator of transcription 3 (STAT3)
pathway in liver fibrogenesis and the anti-fibrotic effect of SHP-1 agonist. The
antifibrotic activity of SC-43, a sorafenib derivative with an enhanced SHP-1
activity, was evaluated in two fibrosis mouse models by carbon tetrachloride
induction and bile duct ligation. Rat, human, and primary mouse hepatic stellate
cells (HSCs) were used for mechanistic investigations. The results showed that
SHP-1 protein primarily localized in fibrotic areas of human and mouse livers. SC
43 treatment reduced the activated HSCs and thus effectively prevented and
regressed liver fibrosis in both fibrosis mouse models and improved mouse
survival. In vitro studies revealed that SC-43 promoted HSC apoptosis, increased
the SHP-1 activity and inhibited phospho-STAT3. The enhanced SHP-1 activity in
HSCs significantly inhibited HSC proliferation, whereas SHP-1 inhibition rescued
SC-43-induced HSC apoptosis. Furthermore, SC-43 interacted with the N-SH2 domain
of SHP-1 to enhance the activity of SHP-1 as its antifibrotic mechanism. In
conclusion, the SHP-1-STAT3 pathway is crucial in fibrogenesis. SC-43
significantly ameliorates liver fibrosis through SHP-1 upregulation. A SHP-1
targeted antifibrotic therapy may represent a druggable strategy for antifibrotic
drug discovery.
PMID- 28496143
TI - Serum Metabolomic Profiles for Breast Cancer Diagnosis, Grading and Staging by
Gas Chromatography-Mass Spectrometry.
AB - Detection of metabolic signature for breast cancer (BC) has the potential to
improve patient prognosis. This study identified potentially significant
metabolites differentiating between breast cancer patients and healthy controls
to help in diagnosis, grading, staging and determination of neoadjuvant status.
Serum was collected from 152 pre-operative breast cancer (BC) patients and 155
healthy controls in this case-controlled study. Gas chromatography-mass
spectrometry (GC-MS) was used to obtain metabolic profiles followed by
chemometric analysis with the identification of significantly differentiated
metabolites including 7 for diagnosis, 18 for grading, 23 for staging, 15 for
stage III subcategory and 10 for neoadjuvant status (p-value < 0.05). Partial
Least Square Discriminant Analysis (PLS-DA) model revealed a distinct separation
between healthy controls and BC patients with a sensitivity of 96% and
specificity of 100% on external validation. Models for grading, staging and
neoadjuvant status were built with Decision Tree Algorithm with predictive
accuracy of 71.5%, 71.3% and 79.8% respectively. Pathway analysis revealed
increased glycolysis, lipogenesis, and production of volatile organic metabolites
indicating the metabolic alterations in breast cancer.
PMID- 28496144
TI - Alkali-created rich properties in grapheme nanoribbons: Chemical bondings.
AB - The alkali-adsorbed graphene nanoribbons exhibit the feature-rich electronic and
magnetic properties. From the first-principles calculations, there are only few
adatom-dominated conduction bands, and the other conduction and valence bands are
caused by carbon atoms. A lot of free electrons are revealed in the occupied
alkali- and carbon-dependent conduction bands. Energy bands are sensitive to the
concentration, distribution and kind of adatom and the edge structure, while the
total linear free carrier density only relies on the first one. These mainly
arise from a single s - 2p z orbital hybridization in the adatom-carbon bond.
Specifically, zigzag systems can present the anti-ferromagnetic ordering across
two edges, ferromagnetic ordering along one edge and non-magnetism, being
reflected in the edge-localized energy bands with or without spin splitting. The
diverse energy dispersions contribute many special peaks in density of states.
The critical chemical bonding and the distinct spin configuration could be
verified from the experimental measurements.
PMID- 28496145
TI - Market watch: Trends in pharmaceutical company R&D spending: 2005-2015.
PMID- 28496147
TI - Combination products: modernizing the regulatory paradigm.
AB - New opportunities to develop innovative - and often complex - products that
combine drugs, devices and/or biological components are rapidly emerging, raising
questions about how such products should be regulated. Here, we discuss the
ongoing efforts of the FDA to develop a modern, transparent, flexible and
consistent science-based regulatory approach for combination products.
PMID- 28496148
TI - Genetic structure of Cercospora beticola populations on Beta vulgaris in New York
and Hawaii.
AB - Cercospora leaf spot (CLS), caused by Cercospora beticola, is a major disease of
Beta vulgaris worldwide. No sexual stage is known for C. beticola but in its
asexual form it overwinters on infected plant debris as pseudostromata, and
travels short distances by rain splash-dispersed conidiospores. Cercospora
beticola infects a broad range of host species and may be seedborne. The relative
contribution of these inoculum sources to CLS epidemics on table beet is not well
understood. Pathogen isolates collected from table beet, Swiss chard and common
lambsquarters in mixed-cropping farms and monoculture fields in New York and
Hawaii, USA, were genotyped (n = 600) using 12 microsatellite markers. All
isolates from CLS symptoms on lambsquarters were identified as C. chenopodii.
Sympatric populations of C. beticola derived from Swiss chard and table beet were
not genetically differentiated. Results suggested that local (within field)
inoculum sources may be responsible for the initiation of CLS epidemics in mixed
cropping farms, whereas external sources of inoculum may be contributing to CLS
epidemics in the monoculture fields in New York. New multiplex PCR assays were
developed for mating-type determination for C. beticola. Implications of these
findings for disease management are discussed.
PMID- 28496146
TI - The antifungal pipeline: a reality check.
AB - Invasive fungal infections continue to appear in record numbers as the
immunocompromised population of the world increases, owing partially to the
increased number of individuals who are infected with HIV and partially to the
successful treatment of serious underlying diseases. The effectiveness of current
antifungal therapies - polyenes, flucytosine, azoles and echinocandins (as
monotherapies or in combinations for prophylaxis, or as empiric, pre-emptive or
specific therapies) - in the management of these infections has plateaued.
Although these drugs are clinically useful, they have several limitations, such
as off-target toxicity, and drug-resistant fungi are now emerging. New
antifungals are therefore needed. In this Review, I discuss the robust and
dynamic antifungal pipeline, including results from preclinical academic efforts
through to pharmaceutical industry products, and describe the targets,
strategies, compounds and potential outcomes.
PMID- 28496149
TI - The active site structure and catalytic mechanism of arsenite oxidase.
AB - Arsenite oxidase is thought to be an ancient enzyme, originating before the
divergence of the Archaea and the Bacteria. We have investigated the nature of
the molybdenum active site of the arsenite oxidase from the Alphaproteobacterium
Rhizobium sp. str. NT-26 using a combination of X-ray absorption spectroscopy and
computational chemistry. Our analysis indicates an oxidized Mo(VI) active site
with a structure that is far from equilibrium. We propose that this is an entatic
state imposed by the protein on the active site through relative orientation of
the two molybdopterin cofactors, in a variant of the Ray-Dutt twist of classical
coordination chemistry, which we call the pterin twist hypothesis. We discuss the
implications of this hypothesis for other putatively ancient molybdopterin-based
enzymes.
PMID- 28496150
TI - Long non-coding RNA PARTICLE bridges histone and DNA methylation.
AB - PARTICLE (Gene PARTICL- 'Promoter of MAT2A-Antisense RadiaTion Induced
Circulating LncRNA) expression is transiently elevated following low dose
irradiation typically encountered in the workplace and from natural sources. This
long non-coding RNA recruits epigenetic silencers for cis-acting repression of
its neighbouring Methionine adenosyltransferase 2A gene. It now emerges that
PARTICLE operates as a trans-acting mediator of DNA and histone lysine
methylation. Chromatin immunoprecipitation sequencing (ChIP-seq) and
immunological evidence established elevated PARTICLE expression linked to
increased histone 3 lysine 27 trimethylation. Live-imaging of dbroccoli-PARTICLE
revealing its dynamic association with DNA methyltransferase 1 was confirmed by
flow cytometry, immunoprecipitation and direct competitive binding interaction
through electrophoretic mobility shift assay. Acting as a regulatory docking
platform, the long non-coding RNA PARTICLE serves to interlink epigenetic
modification machineries and represents a compelling innovative component
necessary for gene silencing on a global scale.
PMID- 28496151
TI - Exploring nonlinear topological states of matter with exciton-polaritons: Edge
solitons in kagome lattice.
AB - Matter in nontrivial topological phase possesses unique properties, such as
support of unidirectional edge modes on its interface. It is the existence of
such modes which is responsible for the wonderful properties of a topological
insulator - material which is insulating in the bulk but conducting on its
surface, along with many of its recently proposed photonic and polaritonic
analogues. We show that exciton-polariton fluid in a nontrivial topological phase
in kagome lattice, supports nonlinear excitations in the form of solitons built
up from wavepackets of topological edge modes - topological edge solitons. Our
theoretical and numerical results indicate the appearance of bright, dark and
grey solitons dwelling in the vicinity of the boundary of a lattice strip. In a
parabolic region of the dispersion the solitons can be described by envelope
functions satisfying the nonlinear Schrodinger equation. Upon collision, multiple
topological edge solitons emerge undistorted, which proves them to be true
solitons as opposed to solitary waves for which such requirement is waived.
Importantly, kagome lattice supports topological edge mode with zero group
velocity unlike other types of truncated lattices. This gives a finer control
over soliton velocity which can take both positive and negative values depending
on the choice of forming it topological edge modes.
PMID- 28496152
TI - Rapid, Self-driven Liquid Mixing on Open-Surface Microfluidic Platforms.
AB - Self-driven surface micromixers (SDSM) relying on patterned-wettability
technology provide an elegant solution for low-cost, point-of-care (POC) devices
and lab-on-a-chip (LOC) applications. We present a SDSM fabricated by
strategically patterning three wettable wedge-shaped tracks onto a non-wettable,
flat surface. This SDSM operates by harnessing the wettability contrast and the
geometry of the patterns to promote mixing of small liquid volumes (uL droplets)
through a combination of coalescence and Laplace pressure-driven flow. Liquid
droplets dispensed on two juxtaposed branches are transported to a coalescence
station, where they merge after the accumulated volumes exceed a threshold.
Further mixing occurs during capillary-driven, advective transport of the
combined liquid over the third wettable track. Planar, non-wettable "islands" of
different shapes are also laid on this third track to alter the flow in such a
way that mixing is augmented. Several SDSM designs, each with a unique
combination of island shapes and positions, are tested, providing a greater
understanding of the different mixing regimes on these surfaces. The study offers
design insights for developing low-cost surface microfluidic mixing devices on
open substrates.
PMID- 28496153
TI - Michaelis-Menten kinetics of soil respiration feedbacks to nitrogen deposition
and climate change in subtropical forests.
AB - China experiences some of the highest rates of anthropogenic nitrogen deposition
globally, with further increases projected. Understanding of soil feedbacks to
the combined anthropogenic influences of climate change and nitrogen deposition
in these systems is critical to improve predictive abilities for future climate
scenarios. Here we used a Michaelis-Menten substrate-based kinetics framework to
explore how soil CO2 production (Rsoil) responds to changes in temperature and
available soil nitrogen (N) by combining field experiments with laboratory
manipulations from sites experiencing elevated rates of anthropogenic N
deposition but varying in soil N availabiltiy. The temperature sensitivity of
Rsoil was strongly influenced by labile C additions. Furthermore, estimation of
the temperature response of the Michaelis-Menten parameters supports the use of
substrate-based kinetics in modeling efforts. Results from both field and
laboratory experiments demonstrated a general decrease in Rsoil with increasing
soil available N that was variably dependent on carbon (C) availability. Both the
field and the laboratory measurements demonstrated a consistent decrease in the
Michaelis-Menten parameter kM with increasing soil available N, indicating an
increase in the efficiency of soil C decomposition with increasing N.
Furthermore, these results provide evidence of interactions between N deposition
and temperature sensitivity, which could influence C storage under combined
anthropogenic global change drivers.
PMID- 28496154
TI - Young children copy cumulative technological design in the absence of action
information.
AB - The ratchet effect - the accumulation of beneficial changes in cultural products
beyond a level that individuals could reach on their own - is a topic of
increasing interest. It is currently debated which social learning mechanisms
allow for the generation and transmission of cumulative culture. This study
focused on transmission, investigating whether 4- to 6-year-old children were
able to copy cumulative technological design and whether they could do so without
action information (emulation). We adapted the spaghetti tower task, previously
used to test for accumulation of culture in human adults. A baseline condition
established that the demonstrated tower design was beyond the innovation skills
of individual children this age and so represented a culture-dependent product
for them. There were 2 demonstration conditions: a full demonstration (actions
plus (end-)results) and an endstate- demonstration (end-results only). Children
in both demonstration conditions built taller towers than those in the baseline.
Crucially, in both demonstration conditions some children also copied the
demonstrated tower. We provide the first evidence that young children learn from,
and that some of them even copy, cumulative technological design, and that - in
line with some adult studies - action information is not always necessary to
transmit culture-dependent traits.
PMID- 28496155
TI - Selection of reference genes for microRNA analysis associated to early stress
response to handling and confinement in Salmo salar.
AB - MicroRNAs are key non-coding RNA molecules that play a relevant role in the
regulation of gene expression through translational repression and/or transcript
cleavage during normal development and physiological adaptation processes like
stress. Quantitative reverse transcription polymerase chain reaction (RT-qPCR)
has become the approach normally used to determine the levels of microRNAs.
However, this approach needs the use of endogenous reference. An improper
selection of endogenous references can result in confusing interpretation of
data. The aim of this study was to identify and validate appropriate endogenous
reference miRNA genes for normalizing RT-qPCR survey of miRNAs expression in four
different tissues of Atlantic salmon, under handling and confinement stress
conditions associated to early or primary stress response. Nine candidate
reference normalizers, including microRNAs and nuclear genes, normally used in
vertebrate microRNA expression studies were selected from literature, validated
by RT-qPCR and analyzed by the algorithms geNorm and NormFinder. The results
revealed that the ssa-miR-99-5p gene was the most stable overall and that ssa-miR
99-5p and ssa-miR-23a-5p genes were the best combination. Moreover, the
suitability of ssa-miR-99-5p and ssa-miR-23a-5p as endogeneuos reference genes
was demostrated by the expression analysis of ssa-miR-193-5p gene.
PMID- 28496156
TI - Hybrid Three-Mode Correlation and Squeezing in a Pr3+:YSO Crystal.
AB - We report the generation of three-mode hybrid intensity-noise correlation and
intensity-difference squeezing of spontaneous parametric four-wave mixing (SP
FWM) and fourth-order fluorescence (FL) signals in the heteronuclear-like (three
level Lambda-type) molecular structure of a Pr3+:Y2SiO5 (Pr3+:YSO) crystal using
the nonlinear cross-Kerr effect under a polarized dressing effect. In the semi
classical view of a Kerr nonlinear medium, the amplitude of two-mode hybrid
correlations of this kind is subject to a limit determined by the hybrid
maximally entangled state. Whereas the degree of correlation and squeezing is
determined by the dressing effects of the input laser fields participating in the
SP-FWM process. We also find that the variations in magnitude of three-mode
hybrid intensity-noise correlation and intensity-difference squeezing are
consistent with nonlinear cross-Kerr processes. Such a three-mode hybrid signal
may have potential applications in long-distance communication, dense coding, all
optical communication and quantum storage on photonic chips.
PMID- 28496157
TI - RNA-Seq based genome-wide analysis reveals loss of inter-chromosomal regulation
in breast cancer.
AB - Breast cancer is a complex heterogeneous disease. Common hallmark features of
cancer can be found. Their origin may be traced back to their intricate
relationships governing regulatory programs during the development of this
disease. To unveil distinctive features of the transcriptional regulation program
in breast cancer, a pipeline for RNA-seq analysis in 780 breast cancer and 101
healthy breast samples, at gene expression and network level, was implemented.
Inter-chromosomal relationships between genes resulted strikingly scarce in a
cancer network, in comparison to its healthy counterpart. We suggest that inter
chromosomal regulation loss may be a novel feature in breast cancer. Additional
evidence was obtained by independent validation in microarray and Hi-C data as
well as supplementary computational analyses. Functional analysis showed
upregulation in processes related to cell cycle and division; while migration,
adhesion and cell-to-cell communication, were downregulated. Both the BRCA1 DNA
repairing signalling and the Estrogen-mediated G1/S phase entry pathways were
found upregulated. In addition, a synergistic underexpression of the gamma
protocadherin complex, located at Chr5q31 is also shown. This region has
previously been reported to be hypermethylated in breast cancer. These findings
altogether provide further evidence for the central role of transcriptional
regulatory programs in shaping malignant phenotypes.
PMID- 28496158
TI - Microbiota: Clostridia protect from gut infections in early life.
PMID- 28496160
TI - Corrigendum: Metal homeostasis and resistance in bacteria.
PMID- 28496161
TI - Bacterial physiology: Hsp90 is the hot guy for Shewanella oneidensis.
PMID- 28496159
TI - A comprehensive guide to pilus biogenesis in Gram-negative bacteria.
AB - Pili are crucial virulence factors for many Gram-negative pathogens. These
surface structures provide bacteria with a link to their external environments by
enabling them to interact with, and attach to, host cells, other surfaces or each
other, or by providing a conduit for secretion. Recent high-resolution structures
of pilus filaments and the machineries that produce them, namely chaperone-usher
pili, type IV pili, conjugative type IV secretion pili and type V pili, are
beginning to explain some of the intriguing biological properties that pili
exhibit, such as the ability of chaperone-usher pili and type IV pili to stretch
in response to external forces. By contrast, conjugative pili provide a conduit
for the exchange of genetic information, and recent high-resolution structures
have revealed an integral association between the pilin subunit and a
phospholipid molecule, which may facilitate DNA transport. In addition, progress
in the area of cryo-electron tomography has provided a glimpse of the overall
architecture of the type IV pilus machinery. In this Review, we examine recent
advances in our structural understanding of various Gram-negative pilus systems
and discuss their functional implications.
PMID- 28496162
TI - Viral pathogenesis: Masked by macrophages.
PMID- 28496163
TI - Reshaping the tree of life.
AB - This month's Genome Watch highlights how metagenomics is continuing to reveal the
diversity of microorganisms in the environment and how it is challenging and
expanding our understanding of how life evolved on Earth.
PMID- 28496164
TI - Biofilms: New ways for streptococci to settle down.
PMID- 28496165
TI - Corrigendum: Assembly, structure, function and regulation of type III secretion
systems.
PMID- 28496166
TI - Measurement of local temperature increments induced by cultured HepG2 cells with
micro-thermocouples in a thermally stabilized system.
AB - To monitor the temperature distribution of a cell and its changes under varied
conditions is currently a technical challenge. A variety of non-contact methods
used for measuring cellular temperature have been developed, where changes of
local temperature at cell-level and sub-cell-level are indirectly calculated
through the changes in intensity, band-shape, bandwidth, lifetime or polarization
anisotropy of the fluorescence spectra recorded from the nano-sized fluorescent
materials pre-injected into the target cell. Unfortunately, the optical
properties of the fluorescent nano-materials may be affected by complicated
intracellular environment, leading to unexpected measurement errors and
controversial arguments. Here, we attempted to offer an alternative approach for
measuring the absolute increments of local temperature in micro-Testing Zones
induced by live cells. In this method, built-in high-performance micro
thermocouple arrays and double-stabilized system with a stability of 10 mK were
applied. Increments of local temperature close to adherent human hepatoblastoma
(HepG2) cells were continuously recorded for days without stimulus, showing
frequent fluctuations within 60 mK and a maximum increment by 285 mK. This method
may open a door for real-time recording of the absolute local temperature
increments of individual cells, therefore offering valuable information for cell
biology and clinical therapy in the field of cancer research.
PMID- 28496168
TI - Biomechanical analysis of prey capture in the carnivorous Southern bladderwort
(Utricularia australis).
AB - We recorded capture events (CEs) of the daphniid Ceriodaphnia dubia by the
carnivorous Southern bladderwort with suction traps (Utricularia australis).
Independent to orientation and behavior during trap triggering, the animals were
successfully captured within 9 ms on average and sucked in with velocities of up
to 4 m/s and accelerations of up to 2800 g. Phases of very high acceleration
during onsets of suction were immediately followed by phases of similarly high
deceleration (max.: -1900 g) inside the bladders, leading to immobilization of
the prey which then dies. We found that traps perform a 'forward strike' during
suction and that almost completely air-filled traps are still able to perform
suction. The trigger hairs on the trapdoors can undergo strong bending
deformation, which we interpret to be a safety feature to prevent fracture. Our
results highlight the elaborate nature of the Utricularia suction traps which are
functionally resilient and leave prey animals virtually no chance to escape.
PMID- 28496167
TI - Effect of Trichoderma harzianum on maize rhizosphere microbiome and biocontrol of
Fusarium Stalk rot.
AB - Fusarium stalk rot (FSR) caused by Fusarium graminearum (FG) significantly
affects the productivity of maize grain crops. Application of agrochemicals to
control the disease is harmful to environment. In this regard, use of biocontrol
agent (BCA) is an alternative to agrochemicals. Although Trichoderma species are
known as BCA, the selection of host-pathogen specific Trichoderma is essential
for the successful field application. Hence, we screened a total of 100
Trichoderma isolates against FG, selected Trichoderma harzianum (CCTCC-RW0024)
for greenhouse experiments and studied its effect on changes of maize rhizosphere
microbiome and biocontrol of FSR. The strain CCTCC-RW0024 displayed high
antagonistic activity (96.30%), disease reduction (86.66%), biocontrol-related
enzyme and gene expression. The root colonization of the strain was confirmed by
eGFP tagging and qRT-PCR analysis. Pyrosequencing revealed that exogenous
inoculation of the strain in maize rhizosphere increased the plant growth
promoting acidobacteria (18.4%), decreased 66% of FG, and also increased the
plant growth. In addition, metabolites of this strain could interact with
pathogenicity related transcriptional cofactor FgSWi6, thereby contributing to
its inhibition. It is concluded that T. harzianum strain CCTCC-RW0024 is a
potential BCA against FSR.
PMID- 28496169
TI - Exploring the link between cadmium and psoriasis in a nationally representative
sample.
AB - Psoriasis, a skin inflammatory disease, originates from dysregulated interactions
of the immune system. Cadmium, an environment pollutant, increases the levels of
inflammation markers and influences the immune system. To clarify the
relationship between cadmium and psoriasis, 5,927 participants, >=20 years, in
the National Health and Nutrition Examination Survey (NHANES) 2003-2006 were
studied. Psoriasis severity was assessed using self-reported dermatology
questionnaires. Cadmium was measured using blood chemistry. Three adjusted models
were applied for the interaction between serum cadmium and severity of psoriasis.
Psoriasis patients had significantly higher blood cadmium (0.67 vs. 0.52 MUg/L, p
= 0.006). There was a strong linear increase in predicted blood cadmium values
with an increase in severity of psoriasis (p for trend = 0.002). The beta
coefficient of the predicted serum cadmium in the "few patches to extensive
psoriasis" group was 0.234 (p = 0.002) after adjusting covariates. Participants
with severe psoriasis have higher blood cadmium. Environmental exposure to
cadmium can predispose to the worsening of psoriasis. Although there are still
limitations in this study, such as not included treatment data, these results
have substantial public health implications for the general population, as they
demonstrate the importance of cadmium exposure prevention, particularly among
psoriasis patients.
PMID- 28496172
TI - Acute D3 Antagonist GSK598809 Selectively Enhances Neural Response During
Monetary Reward Anticipation in Drug and Alcohol Dependence.
PMID- 28496170
TI - Anomalous in-plane anisotropic Raman response of monoclinic semimetal 1 T'-MoTe
2.
AB - The recently discovered two-dimensional (2D) semimetal 1 T'-MoTe2 exhibits
colossal magnetoresistance and superconductivity, driving a strong research
interest in the material's quantum phenomena. Unlike the typical hexagonal
structure found in many 2D materials, the 1 T'-MoTe2 lattice has strong in-plane
anisotropy. A full understanding of the anisotropy is necessary for the
fabrication of future devices which may exploit these quantum and topological
properties, yet a detailed study of the material's anisotropy is currently
lacking. While angle resolved Raman spectroscopy has been used to study
anisotropic 2D materials, such as black phosphorus, there has been no in-depth
study of the Raman dependence of 1 T'-MoTe2 on different layer numbers and
excitation energies. Here, our angle resolved Raman spectroscopy shows intricate
Raman anisotropy dependences of 1 T'-MoTe2 on polarization, flake thickness (from
single layer to bulk), photon, and phonon energies. Using a Paczek approximation,
the anisotropic Raman response can be captured in a classical framework. Quantum
mechanically, first-principle calculations and group theory reveal that the
anisotropic electron-photon and electron-phonon interactions are nontrivial in
the observed responses. This study is a crucial step to enable potential
applications of 1 T'-MoTe2 in novel electronic and optoelectronic devices where
the anisotropic properties might be utilized for increased functionality and
performance.
PMID- 28496171
TI - Altered balance of excitatory and inhibitory learning in a genetically modified
mouse model of glutamatergic dysfunction relevant to schizophrenia.
AB - The GluA1 AMPAR subunit (encoded by the Gria1 gene) has been implicated in
schizophrenia. Gria1 knockout in mice results in recently experienced stimuli
acquiring aberrantly high salience. This suggests that GluA1 may be important for
learning that is sensitive to the temporal contiguity between events. To test
this, mice were trained on a Pavlovian trace conditioning procedure in which the
presentation of an auditory cue and food were separated by a temporal interval.
Wild-type mice initially learnt, but with prolonged training came to withhold
responding during the trace-conditioned cue, responding less than for another cue
that was nonreinforced. Gria1 knockout mice, in contrast, showed sustained
performance over training, responding more to the trace-conditioned cue than the
nonreinforced cue. Therefore, the trace-conditioned cue acquired inhibitory
properties (signalling the absence of food) in wild-type mice, but Gria1 deletion
impaired the acquisition of inhibition, thus maintaining the stimulus as an
excitatory predictor of food. Furthermore, when there was no trace both groups
showed successful learning. These results suggest that cognitive abnormalities in
disorders like schizophrenia in which gluatamatergic signalling is implicated may
be caused by aberrant salience leading to a change in the nature of the
information that is encoded.
PMID- 28496173
TI - Memories of Opiate Withdrawal Emotional States Correlate with Specific Gamma
Oscillations in the Nucleus Accumbens.
PMID- 28496174
TI - NPP: Our Designs for the Future.
PMID- 28496175
TI - Thomas Hanlon.
PMID- 28496176
TI - Efficacy and safety of thiazolidinediones in diabetes patients with renal
impairment: a systematic review and meta-analysis.
AB - We conducted a systematic review and meta-analysis to evaluate the efficacy and
safety of TZDs in treatment of diabetes mellitus patients with renal impairment.
We searched PubMed, EMBASE and Cochrane Central Register of Controlled Trials.
Randomized controlled trials (RCTs), cohort studies, and case-control studies
that investigated the effects of TZDs in patients with diabetes and renal
impairment were eligible. Outcomes included glycosylated hemoglobin, fasting
plasma glucose, serum lipids, and patient-important outcomes (i.e. hypoglycemia,
weight, edema, cardiovascular events and mortality). 19 RCTs and 3 cohort studies
involving 21,803 patients with diabetes and renal impairment were included. Meta
analysis of RCTs showed that TZDs could significantly reduce HbA1c (MD -0.64,
95%CI -0.93 to -0.35), FPG (MD -26.27, 95%CI -44.90 to -7.64) and increase HDL
levels (MD 3.70, 95%CI 1.10, 6.29). TZDs could increase weight (MD 3.23, 95% CI
2.29 to 4.16) and risk of edema (RR 2.96, 95% CI 1.22 to 7.20). Their effects on
risk of hypoglycemia (RR 1.46, 95% CI 0.65 to 3.29), heart failure (RR 0.64, 95%
CI 0.15 to 2.66), angina (RR 1.45, 95% CI 0.23 to 8.95) and all-cause mortality
(RR 0.40, 95% CI 0.08 to 2.01) are uncertain. Results from cohort studies were
similar to RCTs.
PMID- 28496177
TI - Targeting FLT3 by chimeric antigen receptor T cells for the treatment of acute
myeloid leukemia.
PMID- 28496178
TI - Adsorption energy of oxygen molecules on graphene and two-dimensional tungsten
disulfide.
AB - Adsorption of gas molecules on the surface of atomically layered two-dimensional
(2D) materials, including graphene and transition metal dichalcogenides, can
significantly affect their electrical and optical properties. Therefore, a
microscopic and quantitative understanding of the mechanism and dynamics of
molecular adsorption and desorption has to be achieved in order to advance device
applications based on these materials. However, recent theoretical calculations
have yielded contradictory results, particularly on the magnitude of the
adsorption energy. Here, we have experimentally determined the adsorption energy
of oxygen molecules on graphene and 2D tungsten disulfide using temperature
programmed terahertz (THz) emission microscopy (TPTEM). The temperature
dependence of THz emission from InP surfaces covered with 2D materials reflects
the change in oxygen concentration due to thermal desorption, which we used to
estimate the adsorption energy of oxygen molecules on graphene (~0.15 eV) and
tungsten disulphide (~0.24 eV). Furthermore, we used TPTEM to visualize relative
changes in the spatial distribution of oxygen molecules on monolayer graphene
during adsorption and desorption. Our results provide much insight into the
mechanism of molecular adsorption on the surface of 2D materials, while
introducing TPTEM as a novel and powerful tool for molecular surface science.
PMID- 28496179
TI - Microfluidic system for monitoring temporal variations of hemorheological
properties and platelet adhesion in LPS-injected rats.
AB - Sepsis causes multiple organs failures and eventually death. Changes in blood
constituents due to sepsis lead to alterations in hemorheological properties, and
cell adhesiveness. In this study, a new microfluidic system is proposed to
measure temporal variations in biophysical properties of blood after injecting
lipopolysaccharide (LPS) into a rat extracorporeal model under ex vivo condition.
To measure blood viscosity, the interfacial line between blood and a reference
fluid is formed in a Y-shaped channel. Based on the relation between interfacial
width and pressure ratio, the temporal variation in blood viscosity is estimated.
Optical images of blood flows are analyzed by decreasing flow rate for
examination of red blood cell (RBC) aggregation. Platelets initiated by shear
acceleration around the stenosis adhere to the post-stenosed region. By applying
a correlation map that visualizes the decorrelation of the streaming blood flow,
the area of adhered platelets can be quantitatively attained without labeling of
platelets. To assess sepsis inflammation, conventional biomarkers (PCT and IL-8)
are also monitored. The increasing tendency for blood viscosity, RBC aggregation,
platelet adhesion, and septic biomarkers are observed after LPS injection. This
microfluidic system would be beneficial for monitoring the changes in
hemorheological properties and platelet activation caused by sepsis.
PMID- 28496180
TI - Clinicopathologic significance of MYD88 L265P mutation in diffuse large B-cell
lymphoma: a meta-analysis.
AB - The precise clinicopathologic significance of myeloid differentiation primary
response gene (MYD88) L265P mutation in diffuse large B-cell lymphomas (DLBCLs)
remains elusive. To investigate the frequency and clinicopathologic significance
of the MYD88 L265P mutation in DLBCLs, we conducted a meta-analysis of 40
published studies on 2736 DLBCL patients. We collected relevant published
research findings identified using the PubMed and Embase databases. The effect
sizes of outcome parameters were calculated using a random-effects model. In this
meta-analysis, the MYD88 L265P mutation in DLBCL showed a significant difference
according to tumor sites. The overall incidence of the MYD88 L265P mutation in
DLBCLs, excluding the central nervous system and testicular DLBCLs, was 16.5%.
Notably, the MYD88 L265P mutation rates of CNS and testicular DLBCL patients were
60% and 77%, respectively. Interestingly, the MYD88 L265P mutation was more
frequently detected in activated B-cell-like (ABC) or non-germinal center B-cell
like (GCB) than GCB subtype (OR = 3.414, p < 0.001). The MYD88 L265P mutation was
significantly associated with old age and poor overall survival, but not with sex
and clinical stage. This pooled analysis demonstrates that the MYD88 L265P
mutation is significantly associated with the tumor sites and molecular subtypes
in DLBCL patients.
PMID- 28496182
TI - Characterization of off-odours and potentially harmful substances in a fancy
dress accessory handbag for children.
AB - A fancy dress accessory handbag for children was claimed by consumers to exhibit
an offensive smell. Sensory characterization by an expert panel revealed, amongst
others, rubber- and car tire - like notes. For elucidation of the molecular
reasons of this sensory defect, the volatile fraction of the product was isolated
by means of solvent extraction and high vacuum distillation. Identification of
the main odorants was accomplished by means of one- and two-dimensional gas
chromatography, with parallel mass spectrometric and olfactometric detection. In
total more than 60 odorants were detected in the sample and more than 30 of these
odour-active substances could be identified. Amongst them were a number of
naphthalene derivatives as well as saturated and mono- or di-unsaturated carbonyl
compounds. The naphthalene derivatives that were identified in the children's
article appeared to be mainly responsible for the characteristic off-odour.
Additionally, a GC-MS-screening for polycyclic aromatic hydrocarbons (PAHs) was
performed, which revealed the presence of 15 PAHs in total. However, 14 of them
were of no relevance for the smell of the product.
PMID- 28496181
TI - The neuronal K+Cl- co-transporter 2 (Slc12a5) modulates insulin secretion.
AB - Intracellular chloride concentration ([Cl-]i) in pancreatic beta-cells is kept
above electrochemical equilibrium due to the predominant functional presence of
Cl- loaders such as the Na+K+2Cl- co-transporter 1 (Slc12a2) over Cl-extruders of
unidentified nature. Using molecular cloning, RT-PCR, Western blotting,
immunolocalization and in vitro functional assays, we establish that the "neuron
specific" K+Cl- co-transporter 2 (KCC2, Slc12a5) is expressed in several
endocrine cells of the pancreatic islet, including glucagon secreting alpha
cells, but particularly in insulin-secreting beta-cells, where we provide
evidence for its role in the insulin secretory response. Three KCC2 splice
variants were identified: the formerly described KCC2a and KCC2b along with a
novel one lacking exon 25 (KCC2a-S25). This new variant is undetectable in brain
or spinal cord, the only and most abundant known sources of KCC2. Inhibition of
KCC2 activity in clonal MIN6 beta-cells increases basal and glucose-stimulated
insulin secretion and Ca2+ uptake in the presence of glibenclamide, an inhibitor
of the ATP-dependent potassium (KATP)-channels, thus suggesting a possible
mechanism underlying KCC2-dependent insulin release. We propose that the long
time considered "neuron-specific" KCC2 co-transporter is expressed in pancreatic
islet beta-cells where it modulates Ca2+-dependent insulin secretion.
PMID- 28496183
TI - Everyday cognition scales are related to cognitive function in the early stage of
probable Alzheimer's disease and FDG-PET findings.
AB - We applied the Everyday Cognition (ECog) scale in normal aging adults and
patients with Alzheimer's disease (AD) to investigate associations between
neuropsychological tests and neuroimaging markers. A total of 160 normal aging
adults and 40 patients with the early stage of probable AD were included.
Neuropsychological performance was assessed using the Consortium to Establish a
Registry for Alzheimer's Disease Neuropsychological Assessment Battery (CERAD
NAB). 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scans were
used to measure AD-related hypometabolism. Nonparametric Spearman correlation
analysis was used to study associations between ECog and z-transformed total
CERAD-NAB scores in both groups. The results revealed a significant correlation
between total ECog and CERAD-NAB scores (rho = -0.28, p < 0.01), and category
verbal fluency test with the executive domain of the ECog scale (rho = -0.20, p <
0.01). The CERAD-NAB scores were also significantly correlated with AD-related
hypometabolism (rho = -0.49, p < 0.01). The memory domain of the ECog scale was
significantly correlated with FDG uptake in the angular gyrus and posterior
cingulum gyrus (rho = -0.41 and -0.46, P < 0.01). In conclusion, both total and
memory domain ECog scores were correlated with the neuropsychological tests and
neuroimaging biomarkers.
PMID- 28496184
TI - El Nino increases the risk of lower Mississippi River flooding.
AB - Mississippi River floods rank among the costliest climate-related disasters in
the world. Improving flood predictability, preparedness, and response at seasonal
to decadal time-scales requires an understanding of the climatic controls that
govern flood occurrence. Linking flood occurrence to persistent modes of climate
variability like the El Nino-Southern Oscillation (ENSO) has proven challenging,
due in part to the limited number of high-magnitude floods available for study in
the instrumental record. To augment the relatively short instrumental record, we
use output from the Community Earth System Model (CESM) Last Millennium Ensemble
(LME) to investigate the dynamical controls on discharge extremes of the lower
Mississippi River. We show that through its regional influence on surface water
storage, the warm phase of ENSO preconditions the lower Mississippi River to be
vulnerable to flooding. In the 6-12 months preceding a flood, El Nino generates a
positive precipitation anomaly over the lower Mississippi basin that gradually
builds up soil moisture and reduces the basin's infiltration capacity, thereby
elevating the risk of a major flood during subsequent rainstorms. Our study
demonstrates how natural climate variability mediates the formation of extreme
floods on one of the world's principal commercial waterways, adding significant
predictive ability to near- and long-term forecasts of flood risk.
PMID- 28496185
TI - 'Gardos Channelopathy': a variant of hereditary Stomatocytosis with complex
molecular regulation.
AB - The Gardos channel is a Ca2+ sensitive, K+ selective channel present in several
tissues including RBCs, where it is involved in cell volume regulation. Recently,
mutations at two different aminoacid residues in KCNN4 have been reported in
patients with hereditary xerocytosis. We identified by whole exome sequencing a
new family with two members affected by chronic hemolytic anemia carrying
mutation R352H in the KCNN4 gene. No additional mutations in genes encoding for
RBCs cytoskeletal, membrane or channel proteins were detected. We performed
functional studies on patients' RBCs to evaluate the effects of R352H mutation on
the cellular properties and eventually on the clinical phenotype. Gardos channel
hyperactivation was demonstrated in circulating erythrocytes and erythroblasts
differentiated ex-vivo from peripheral CD34+ cells. Pathological alterations in
the function of multiple ion transport systems were observed, suggesting the
presence of compensatory effects ultimately preventing cellular dehydration in
patient's RBCs; moreover, flow cytometry and confocal fluorescence live-cell
imaging showed Ca2+ overload in the RBCs of both patients and hypersensitivity of
Ca2+ uptake by RBCs to swelling. Altogether these findings suggest that the
'Gardos channelopathy' is a complex pathology, to some extent different from the
common hereditary xerocytosis.
PMID- 28496186
TI - An ancient selective sweep linked to reproductive life history evolution in
sockeye salmon.
AB - Study of parallel (or convergent) phenotypic evolution can provide important
insights into processes driving sympatric, ecologically-mediated divergence and
speciation, as ecotype pairs may provide a biological replicate of the underlying
signals and mechanisms. Here, we provide evidence for a selective sweep creating
an island of divergence associated with reproductive behavior in sockeye salmon
(Oncorhynchus nerka), identifying a series of linked single nucleotide
polymorphisms across a ~22,733 basepair region spanning the leucine-rich repeat
containing protein 9 gene exhibiting signatures of divergent selection associated
with stream- and shore-spawning in both anadromous and resident forms across
their pan-Pacific distribution. This divergence likely occurred ~3.8 Mya (95% HPD
= 2.1-6.03 Mya), after sockeye separated from pink (O. gorbuscha) and chum (O.
keta) salmon, but prior to the Pleistocene glaciations. Our results suggest
recurrent evolution of reproductive ecotypes across the native range of O. nerka
is at least partially associated with divergent selection of pre-existing genetic
variation within or linked to this region. As sockeye salmon are unique among
Pacific salmonids in their flexibility to spawn in lake-shore benthic
environments, this region provides great promise for continued investigation of
the genomic basis of O. nerka life history evolution, and, more broadly, for
increasing our understanding of the heritable basis of adaptation of complex
traits in novel environments.
PMID- 28496187
TI - Geometric explanation of the rich-club phenomenon in complex networks.
AB - The rich club organization (the presence of highly connected hub core in a
network) influences many structural and functional characteristics of networks
including topology, the efficiency of paths and distribution of load. Despite its
major role, the literature contains only a very limited set of models capable of
generating networks with realistic rich club structure. One possible reason is
that the rich club organization is a divisive property among complex networks
which exhibit great diversity, in contrast to other metrics (e.g. diameter,
clustering or degree distribution) which seem to behave very similarly across
many networks. Here we propose a simple yet powerful geometry-based growing model
which can generate realistic complex networks with high rich club diversity by
controlling a single geometric parameter. The growing model is validated against
the Internet, protein-protein interaction, airport and power grid networks.
PMID- 28496188
TI - Preclinical evaluation of PAC1 targeting with radiolabeled Maxadilan.
AB - There is an ongoing search for new tracers to optimize imaging of beta cell
derived tumors (insulinomas). The PAC1 receptor, expressed by insulinomas, can be
used for targeting of these tumors. Here, we investigated whether radiolabeled
maxadilan could be used for insulinoma imaging. Maxadilan was C- or N-terminally
conjugated with DTPA (termed maxadilan-DPTA or DTPA-maxadilan respectively).
BALB/c nude mice bearing subcutaneous INS-1 tumors were injected with either In
111-labeled maxadilan-DTPA or In-111-DTPA-maxadilan. Biodistribution studies were
carried out at 1, 2 and 4 hours after injection and SPECT/CT imaging 1 and 4
hours after injection of maxadilan-DTPA-111In. Radiolabeling of maxadilan-DTPA
(680 MBq/nmol) was more efficient than of DTPA-maxadilan (55 MBq/nmol).
Conjugation with DTPA slightly reduced receptor binding affinity in vitro: IC50
values were 3.2, 21.0 and 21.0 nM for maxadilan, natIn-DTPA-maxadilan and
maxadilan-DTPA-natIn respectively. Upon i.v. injection maxadilan-DTPA-111In
accumulated specifically in INS-1 tumors (7.30 +/- 1.87%ID/g) and in the pancreas
(3.82 +/- 0.22%ID/g). INS-1 tumors were clearly visualized by small animal
SPECT/CT. In conclusion, this study showed that the high affinity of maxadilan to
the PAC1 receptor was maintained after DTPA conjugation. Furthermore,
radiolabeled maxadilan-DTPA accumulated specifically in INS-1 tumors and,
therefore, may qualify as a useful tracer to image insulinomas.
PMID- 28496189
TI - Impacts of carbon nanomaterials on the diversity of microarthropods in turfgrass
soil.
AB - Nanoscale materials have been produced with unprecedented speed due to their
widespread use, and they may eventually be released into the environment. As
effective adsorbents for heavy metals, carbon nanomaterials can be used to
immobilize metals in contaminated soil, but little information is available
regarding their effects on soil microarthropods. This study was designed to
investigate the influence of three types of carbon nanomaterials, graphene (G),
graphene oxide (GO) and carbon nanotubes (CNTs) on soil microarthropod
communities under turfgrass growth conditions. The application of carbon
nanomaterials resulted in increased abundance of all soil microarthropods,
especially in the GO and CNT treatments. GO also significantly increased the
abundances of multiple trophic functional groups, including predators,
detritivores, herbivores and fungivores. Further, the dominant genera varied
among the treatments. Herbivorous microarthropods predominated in the control,
whereas predatory species predominated in the carbon nanomaterial treatments.
Carbon nanomaterials also increased the total taxonomic richness, Shannon
diversity index, and dominance index of the microarthropod community, but they
decreased the evenness index. Higher diversity of soil microarthropods indicates
an environment suitable for soil mesofauna and for enhanced decomposition and
nutrient cycling in the soil food web.
PMID- 28496191
TI - Breed, sex, and litter effects in 2-month old puppies' behaviour in a
standardised open-field test.
AB - A considerable number of studies have reported differences among dog breeds with
respect to their genetic profile, cognitive abilities or personality traits. Each
dog breed is normally treated as a homogeneous group, however, researchers have
recently questioned whether the behavioural profile of modern breeds still
reflects their historical function or if the intense divergent selective
pressures and geographical barriers have created a more fragmented picture. The
majority of studies attempting to assess and compare modern breeds' personality
focused on the evaluation of adult dogs where the potential effects of
environmental/human factors on the dogs' behaviour are hard to discern from their
genetic heritage. In the following study, we aimed at investigating between- and
within-breed differences in the personality of two-months-old puppies by direct
behavioural observation of 377 puppies from 12 breeds. Results showed that there
was no effect of sex, however both breed and litter, significantly affected all
personality traits. Breed on average explained 10% of the variance, whereas the
effect of litter was noticeably higher, explaining on average 23% of the
variance. Taken together, our results suggest that breed does have some influence
on personality traits, but they also highlight the importance of taking litter
effects into account.
PMID- 28496190
TI - Beta-agonist overuse and delay in obtaining medical review in high risk asthma: a
secondary analysis of data from a randomised controlled trial.
AB - : Asthma mortality surveys report delays in seeking medical review and overuse of
beta-agonist therapy as factors contributing to a fatal outcome. However, the
strength of these associations is limited because many asthma deaths are
unwitnessed. We undertook a secondary analysis of data from a 24-week randomised
controlled trial of 303 patients with high-risk asthma, randomised to combination
budesonide/formoterol inhaler according to a single maintenance and reliever
therapy regimen or fixed dose budesonide/formoterol with salbutamol as reliever
(Standard) regimen. Medication use was measured by electronic monitors. The
thresholds for high, marked and extreme beta-agonist use days were defined in the
single maintenance and reliever therapy arm as: >8, >12 and >16 actuations of
budesonide/formoterol in excess of four maintenance doses, respectively; and in
the Standard arm as: >16, >24 and >32 actuations of salbutamol, respectively.
Whether a medical review was obtained within 48 h of an overuse episode was
determined by review of data collected during the study by participant report.
The mean (standard deviation) proportion of days in which high, marked and
extreme beta-agonist overuse occurred without medical review within 48 h was
0.94(0.20), 0.94(0.15) and 0.94(0.17), and 0.92(0.19), 0.90(0.26) and 0.94(0.15)
for single maintenance and reliever therapy and Standard regimens, respectively.
In at least 90% of days, in which beta-agonist overuse occurred, patients did not
obtain medical review within 48 h of beta-agonist overuse, regardless of the
magnitude of overuse or the inhaled corticosteroid/long-acting beta-agonist
regimen. RELIEVER INHALER OVERUSE AND DELAY IN MEDICAL REVIEW IN ASTHMA: In
asthma, overuse of beta-agonist reliever medication and delay in seeking medical
review in an exacerbation are linked to asthma deaths. Janine Pilcher at the
Medical Research Institute of New Zealand, and co-workers, conducted a review of
data from a study of 303 adult patients with severe asthma, followed over 24
weeks. The patients were allocated to either a budesonide/formoterol, or a
salbutamol inhaler to take for symptom relief, in addition to their maintenance
treatment. Inhalers were fitted with electronic monitors, to accurately document
every use. In both groups, on 90% of days when an exacerbation requiring excess
use of an inhaler occurred, patients did not follow-up with medical professionals
within 48 h as advised. Further, in both groups, 'extreme' reliever inhaler use
was recorded at least once in around one in four patients.
PMID- 28496192
TI - Magnetic field tuning of an excitonic insulator between the weak and strong
coupling regimes in quantum limit graphite.
AB - The excitonic insulator phase has long been predicted to form in proximity to a
band gap opening in the underlying band structure. The character of the pairing
is conjectured to crossover from weak (BCS-like) to strong coupling (BEC-like) as
the underlying band structure is tuned from the metallic to the insulating side
of the gap opening. Here we report the high-magnetic field phase diagram of
graphite to exhibit just such a crossover. By way of comprehensive angle-resolved
magnetoresistance measurements, we demonstrate that the underlying band gap
opening occurs inside the magnetic field-induced phase, paving the way for a
systematic study of the BCS-BEC-like crossover by means of conventional condensed
matter probes.
PMID- 28496193
TI - Exendin-4 Exhibits Enhanced Anti-tumor Effects in Diabetic Mice.
AB - Type 2 diabetes (T2D) is associated with increased risk of cancers. In this
connection, we previously demonstrated the promoting effect of diabetes on HPV
associated carcinogenesis using a xenograft model in db/db diabetic mice. The
underlying mechanism of this observation might be partly contributed by
dysregulated immune response in diabetes. In this study, we hypothesized that the
impaired anti-tumor immune response in diabetic status could be modulated by
exendin-4, a glucagon-like protein receptor agonist which exhibits anti-diabetic
effects. We inoculated 10-week old db/db mice with 2 * 107 CUP-1 cells (Human
Papilloma Virus (HPV)-16 E7 transfected continuous cell line) subcutaneously
underneath the scruff, and treated mice with high (30 nmol/kg) or low (10
nmol/kg) dose of exendin-4 for 13 days. Compared with control groups, exendin-4
suppressed subcutaneous tumor growth in a dose-dependent manner, accompanied by
increased interferon (IFN)-gamma secreting CD8+ cytotoxic T lymphocyte
(CTL)/Foxp3+ regulatory T cell (Treg) ratio as well as Th1 proinflammatory
cytokines IFN-gamma and IL-2. Collectively, these findings suggested an anti
tumor effect of exendin-4 in diabetic conditions, which might be resulted from
direct immunomodulation.
PMID- 28496194
TI - Zooplankton Community Profiling in a Eutrophic Freshwater Ecosystem-Lake Tai
Basin by DNA Metabarcoding.
AB - Communities of zooplankton, a critical portion of aquatic ecosystems, can be
adversely affected by contamination resulting from human activities.
Understanding the influence of environmental change on zooplankton communities
under field-conditions is hindered by traditional labor-intensive approaches that
are prone to taxonomic and enumeration mistakes. Here, metabarcoding of
cytochrome c oxidase I (COI) region of mitochondrial DNA was used to characterize
the genetic diversity of zooplankton. The species composition of zooplankton
communities determined by metabarcoding was consistent with the results based on
the traditional morphological approach. The spatial distribution of common
species (frequency of occurrence >10 samples) by metabarcoding exhibited good
agreement with morphological data. Furthermore, metabarcoding can clearly
distinguish the composition of the zooplankton community between lake and river
ecosystems. In general, rotifers were more abundant in riverine environments than
lakes and reservoirs. Finally, the sequence read number of different taxonomic
groups using metabarcoding was positively correlated with the zooplankton biomass
inferred by density and body length of zooplankton. Overall, the utility of
metabarcoding for taxonomic profiling of zooplankton communities was validated by
the morphology-based method on a large ecological scale. Metabarcoding of COI
could be a powerful and efficient biomonitoring tool to protect local aquatic
ecosystems.
PMID- 28496195
TI - Symmetry breaking during homodimeric assembly activates an E3 ubiquitin ligase.
AB - C-terminus of Hsc/p70-Interacting Protein (CHIP) is a homodimeric E3 ubiquitin
ligase. Each CHIP monomer consists of a tetratricopeptide-repeat (TPR), helix
turn-helix (HH), and U-box domain. In contrast to nearly all homodimeric
proteins, CHIP is asymmetric. To uncover the origins of asymmetry, we performed
molecular dynamics simulations of dimer assembly. We determined that a CHIP
monomer is most stable when the HH domain has an extended helix that supports
intra-monomer TPR-U-box interaction, blocking the E2-binding surface of the U
box. We also discovered that monomers first dimerize symmetrically through their
HH domains, which then triggers U-box dimerization. This brings the extended
helices into close proximity, including a repulsive stretch of positively charged
residues. Unable to smoothly unwind, this conflict bends the helices until the
helix of one protomer breaks to relieve the repulsion. The abrupt snapping of the
helix forces the C-terminal residues of the other protomer to disrupt that
protomer's TPR-U-box tight binding interface, swiftly exposing and activating one
of the E2 binding sites. Mutagenesis and biochemical experiments confirm that C
terminal residues are necessary both to maintain CHIP stability and function.
This novel mechanism indicates how a ubiquitin ligase maintains an inactive
monomeric form that rapidly activates only after asymmetric assembly.
PMID- 28496196
TI - TaPIMP2, a pathogen-induced MYB protein in wheat, contributes to host resistance
to common root rot caused by Bipolaris sorokiniana.
AB - MYB transcription factors (TFs) have been implicated in various biology processes
in model plants. However, functions of the great majority of MYB TFs in wheat
(Triticum aestivum L.) have not been characterized. The soil-borne fungal
pathogens Bipolaris sorokiniana and Rhizoctonia cerealis are the causal agents of
important destructive diseases of wheat. Here, the TaPIMP2 gene, encoding a
pathogen-induced MYB protein in wheat, was isolated through comparative
transcriptomic analysis, and its defensive role was studied. TaPIMP2 was proved
to localize in nuclei. TaPIMP2 responded in a different extent and speed upon
infections of B. sorokiniana or R. cerealis. TaPIMP2 displayed different
expression patterns after exogenous application of phytohormones, including
abscisic acid, ethylene, and salicylic acid. Silencing of TaPIMP2 repressed
resistance of wheat cultivar Yangmai 6 to B. sorokiniana, but did not alter
resistance of wheat line CI12633 to R. cerealis. TaPIMP2 overexpression
significantly improved resistance to B. sorokiniana rather than R. cerealis in
transgenic wheat. Moreover, TaPIMP2 positively modulated the expression of
pathogenesis-related genes, including PR1a, PR2, PR5, and PR10. Collectively,
TaPIMP2 positively contributes to wheat resistance to B. sorokiniana possibly
through regulating the expression of defense-related genes, and TaPIMP2 plays
distinct roles in defense responses to different fungal infection.
PMID- 28496197
TI - Helicobacter pylori-derived extracellular vesicles increased in the gastric
juices of gastric adenocarcinoma patients and induced inflammation mainly via
specific targeting of gastric epithelial cells.
AB - Evidence indicates that Helicobacter pylori is the causative agent of chronic
gastritis and perhaps gastric malignancy. Extracellular vesicles (EVs) play an
important role in the evolutional process of malignancy due to their genetic
material cargo. We aimed to evaluate the clinical significance and biological
mechanism of H. pylori EVs on the pathogenesis of gastric malignancy. We
performed 16S rDNA-based metagenomic analysis of gastric juices either from
endoscopic or surgical patients. From each sample of gastric juices, the bacteria
and EVs were isolated. We evaluated the role of H. pylori EVs on the development
of gastric inflammation in vitro and in vivo. IVIS spectrum and confocal
microscopy were used to examine the distribution of EVs. The metagenomic analyses
of the bacteria and EVs showed that Helicobacter and Streptococcus are the two
major bacterial genera, and they were significantly increased in abundance in
gastric cancer (GC) patients. H. pylori EVs are spherical and contain CagA and
VacA. They can induce the production of tumor necrosis factor-alpha, interleukin
(IL)-6 and IL-1beta by macrophages, and IL-8 by gastric epithelial cells. Also,
EVs induce the expression of interferon gamma, IL-17 and EV-specific
immunoglobulin Gs in vivo in mice. EVs were shown to infiltrate and remain in the
mouse stomach for an extended time. H. pylori EVs, which are abundant in the
gastric juices of GC patients, can induce inflammation and possibly cancer in the
stomach, mainly via the production of inflammatory mediators from gastric
epithelial cells after selective uptake by the cells.
PMID- 28496198
TI - Bone-forming peptide-2 derived from BMP-7 enhances osteoblast differentiation
from multipotent bone marrow stromal cells and bone formation.
AB - Strategies for efficient osteogenic differentiation and bone formation from stem
cells would have clinical applications in treating nonunion fracture healing.
Many researchers have attempted to develop adjuvants as specific stimulators of
bone formation for therapeutic use in patients with bone resorption. Therefore,
development of specific stimulators of bone formation has therapeutic
significance in the treatment of osteoporosis. To date, investigations of the
mature forms of bone morphogenetic proteins (BMPs) have focused on regulation of
bone generation. However, we previously identified new peptides from the immature
precursor of BMP, and further analysis of these proteins should be performed. In
this study, we identified a new peptide called bone-forming peptide-2 (BFP-2),
which has stronger osteogenic differentiation-promoting activity than BMP-7. BFP
2 treatment of multipotent bone marrow stromal cells (BMSCs) induced expression
of active alkaline phosphatase. In addition, BFP-2 enhanced CD44 and CD51
expression levels and increased Ca2+ content in BMSCs. Moreover, radiography at 8
weeks revealed that animals that had received transplants of BFP-2-treated BMSCs
showed substantially increased bone formation compared with animals that had
received BMSCs treated with BMP-7. Our findings indicate that BFP-2 may be useful
in the development of adjuvant therapies for bone-related diseases.
PMID- 28496199
TI - Upregulation and biological function of transmembrane protein 119 in
osteosarcoma.
AB - Osteosarcoma is suggested to be caused by genetic and molecular alterations that
disrupt osteoblast differentiation. Recent studies have reported that
transmembrane protein 119 (TMEM119) contributes to osteoblast differentiation and
bone development. However, the level of TMEM119 expression and its roles in
osteosarcoma have not yet been elucidated. In the present study, TMEM119 mRNA and
protein expression was found to be up-regulated in osteosarcoma compared with
normal bone cyst tissues. The level of TMEM119 protein expression was strongly
associated with tumor size, clinical stage, distant metastasis and overall
survival time. Moreover, gene set enrichment analysis (GSEA) of the Gene
Expression Omnibus (GEO) GSE42352 dataset revealed TMEM119 expression in
osteosarcoma tissues to be positively correlated with cell cycle, apoptosis,
metastasis and TGF-beta signaling. We then knocked down TMEM119 expression in
U2OS and MG63 cells using small interfering RNA, which revealed that
downregulation of TMEM119 could inhibit the proliferation of osteosarcoma cells
by inducing cell cycle arrest in G0/G1 phase and apoptosis. We also found that
TMEM119 knockdown significantly inhibited cell migration and invasion, and
decreased the expression of TGF-beta pathway-related factors (BMP2, BMP7 and TGF
beta). TGF-beta application rescued the inhibitory effects of TMEM119 knockdown
on osteosarcoma cell migration and invasion. Further in vitro experiments with a
TGF-beta inhibitor (SB431542) or BMP inhibitor (dorsomorphin) suggested that
TMEM119 significantly promotes cell migration and invasion, partly through TGF
beta/BMP signaling. In conclusion, our data support the notion that TMEM119
contributes to the proliferation, migration and invasion of osteosarcoma cells,
and functions as an oncogene in osteosarcoma.
PMID- 28496200
TI - microRNA-200a-3p increases 5-fluorouracil resistance by regulating dual
specificity phosphatase 6 expression.
AB - Acquisition of resistance to anti-cancer drugs is a significant obstacle to
effective cancer treatment. Although several efforts have been made to overcome
drug resistance in cancer cells, the detailed mechanisms have not been fully
elucidated. Here, we investigated whether microRNAs (miRNAs) function as pivotal
regulators in the acquisition of anti-cancer drug resistance to 5-fluorouracil (5
FU). A survey using a lentivirus library containing 572 precursor miRNAs revealed
that five miRNAs promoted cell survival after 5-FU treatment in human
hepatocellular carcinoma Hep3B cells. Among the five different clones, the clone
expressing miR-200a-3p (Hep3B-miR-200a-3p) was further characterized as a 5-FU
resistant cell line. The cell viability and growth rate of Hep3B-miR-200a-3p
cells were higher than those of control cells after 5-FU treatment. Ectopic
expression of a miR-200a-3p mimic increased, while inhibition of miR-200a-3p
downregulated, cell viability in response to 5-FU, doxorubicin, and CDDP
(cisplatin). We also showed that dual-specificity phosphatase 6 (DUSP6) is a
novel target of miR-200a-3p and regulates resistance to 5-FU. Ectopic expression
of DUSP6 mitigated the pro-survival effects of miR-200a-3p. Taken together, these
results lead us to propose that miR-200a-3p enhances anti-cancer drug resistance
by decreasing DUSP6 expression.
PMID- 28496201
TI - Engulfment signals and the phagocytic machinery for apoptotic cell clearance.
AB - The clearance of apoptotic cells is an essential process for tissue homeostasis.
To this end, cells undergoing apoptosis must display engulfment signals, such as
'find-me' and 'eat-me' signals. Engulfment signals are recognized by multiple
types of phagocytic machinery in phagocytes, leading to prompt clearance of
apoptotic cells. In addition, apoptotic cells and phagocytes release tolerogenic
signals to reduce immune responses against apoptotic cell-derived self-antigens.
Here we discuss recent advances in our knowledge of engulfment signals, the
phagocytic machinery and the signal transduction pathways for apoptotic cell
engulfment.
PMID- 28496203
TI - Common Variants in OPG Confer Risk to Bone Mineral Density Variation and
Osteoporosis Fractures.
AB - Although many common variants have been identified for bone mineral density (BMD)
and osteoporosis fractures, all the identified risk variants could only explain a
small portion of heritability of BMD and osteoporosis fractures. OPG belongs to
the tumor necrosis factor receptor superfamily, which plays a crucial role in
bone remodeling and is thus a promising candidate gene of osteoporosis. Several
studies have explored the association of OPG variants with BMD or osteoporosis
fractures, however, the results remain inconsistent among different populations.
In the study, we first assessed the relationship between OPG variants and BMD or
osteoporosis fractures in our sample size (227 subjects with postmenopausal
osteoporosis and 189 controls), and then performed a systematic meta-analysis.
Among the nine SNPs genotyped, rs6469804 and rs2073618 showed significant
associations with both BMD and osteoporotic fractures, while rs3102735 was only
associated with BMD in our samples (P < 0.05). For meta-analyses, data for a
total of 12 SNPs were pooled (4725 patients and 37804 controls), and five SNPs,
including rs6993813, rs6469804, rs3134070, rs2073618 and rs3102734, showed
association with osteoporosis fractures (P < 0.05). On light of the above
analysis, we believe that OPG is one promising susceptibility gene of BMD or
osteoporotic fractures.
PMID- 28496202
TI - Inhibition of Jak/STAT signaling reduces the activation of pancreatic stellate
cells in vitro and limits caerulein-induced chronic pancreatitis in vivo.
AB - Chronic pancreatitis (CP) is a fibro-inflammatory disease leading to pain,
maldigestion, and pancreatic insufficiency. No therapeutic options exist due to a
limited understanding of the biology of CP pathology. Recent findings implicate
pancreatic stellate cells (PSC) as prominent mediators of inflammatory and
fibrotic processes during CP. Here, we utilized primary and immortalized PSC
obtained from mice and patients with CP or pancreatic cancer to examine the
effect of Jak/STAT and MAPK pathway inhibition in vitro. The well-characterized
caerulein model of CP was used to assess the therapeutic efficacy of Jak1/2
inhibition in vivo. Treatment of cultured PSC with the Jak1/2 inhibitor
ruxolitinib reduced STAT3 phosphorylation, cell proliferation, and expression of
alpha-smooth muscle actin (alpha-SMA), a marker of PSC activation. Treatment with
the MAPK inhibitor, MEK162, had less consistent effects on PSC proliferation and
no impact on activation. In the caerulein-induced murine model of CP,
administration of ruxolitinib for one week significantly reduced biomarkers of
inflammation and fibrosis. These data suggest that the Jak/STAT pathway plays a
prominent role in PSC proliferation and activation. In vivo treatment with the
Jak1/2 inhibitor ruxolitinib reduced the severity of experimental CP, suggesting
that targeting Jak/STAT signaling may represent a promising therapeutic strategy
for CP.
PMID- 28496204
TI - A Photochemical Avenue to Photoluminescent N-Dots and their Upconversion Cell
Imaging.
AB - A photochemical avenue to synthesize nitrogen-rich quantum dots (N-dots) using 2
azido imidazole as the starting material was established for the first time. A
production yield of up to 92.7% was obtained. The N-dots were then fully
characterized by elemental analysis, IR, XPS, XRD, AFM and TEM. On the basis of
the N2 production and in situ IR results, the underlying mechanism for the
photochemical formation of N-dots was proposed. These N-dots showed promising
optical properties including wavelength-dependent upconversion photoluminescence,
and were successfully used in upconversion cell imaging.
PMID- 28496205
TI - Characterisation of a 3-hydroxypropionic acid-inducible system from Pseudomonas
putida for orthogonal gene expression control in Escherichia coli and Cupriavidus
necator.
AB - 3-hydroxypropionic acid (3-HP) is an important platform chemical used as a
precursor for production of added-value compounds such as acrylic acid.
Metabolically engineered yeast, Escherichia coli, cyanobacteria and other
microorganisms have been developed for the biosynthesis of 3-HP. Attempts to
overproduce this compound in recombinant Pseudomonas denitrificans revealed that
3-HP is consumed by this microorganism using the catabolic enzymes encoded by
genes hpdH, hbdH and mmsA. 3-HP-inducible systems controlling the expression of
these genes have been predicted in proteobacteria and actinobacteria. In this
study, we identify and characterise 3-HP-inducible promoters and their
corresponding LysR-type transcriptional regulators from Pseudomonas putida
KT2440. A newly-developed modular reporter system proved possible to demonstrate
that PpMmsR/P mmsA and PpHpdR/P hpdH are orthogonal and highly inducible by 3-HP
in E. coli (12.3- and 23.3-fold, respectively) and Cupriavidus necator (51.5- and
516.6-fold, respectively). Bioinformatics and mutagenesis analyses revealed a
conserved 40-nucleotide sequence in the hpdH promoter, which plays a key role in
HpdR-mediated transcription activation. We investigate the kinetics and dynamics
of the PpHpdR/P hpdH switchable system in response to 3-HP and show that it is
also induced by both enantiomers of 3-hydroxybutyrate. These findings pave the
way for use of the 3-HP-inducible system in synthetic biology and biotechnology
applications.
PMID- 28496206
TI - WISP1/CCN4 inhibits adipocyte differentiation through repression of PPARgamma
activity.
AB - WISP1 (Wnt1-inducible signaling pathway protein-1, also known as CCN4) is a
member of the CCN family able to mediate cell growth, transformation and survival
in a tissue-specific manner. Here, we report that WISP1 expression was highly
increased in preadipocytes and decreased during adipocyte differentiation.
Moreover, we observed an increase in WISP1 gene expression in adipose tissue from
both diet-induced and leptin-deficient ob/ob obese mice, suggesting that WISP1
could be involved in the pathophysiological onset of obesity. Interestingly,
overexpression of WISP1 in 3T3-F442A cells prevented adipocyte differentiation
via downregulation of peroxisome proliferator-activated receptor (PPARgamma)
transcriptional activity thereby attenuating the expression of adipogenic
markers. Conversely, silencing of WISP1 enhanced adipocyte differentiation. We
further show that the inactivation of PPARgamma transcriptional activity was
mediated, at least in part, by a direct physical association between WISP1 and
PPARgamma, followed by proteasome-dependent degradation of PPARgamma. These
results suggest for the first time that WISP1 interacts with PPARgamma and that
this interaction results in the inhibition of PPARgamma activity. Taken together
our results suggest that WISP1 functions as a negative regulator of adipogenesis.
PMID- 28496207
TI - Selective doping of Ni2+ in highly transparent glass-ceramics containing nano
spinels ZnGa2O4 and Zn1+x Ga2-2x Ge x O4 for broadband near-infrared fiber
amplifiers.
AB - Selective doping of Ni2+ in octahedral sites provided by nanocrystals embedded in
glass-ceramics (GCs) is crucial to the enhancement of broadband near-infrared
(NIR) emission. In this work, a NIR emission with a full-width-at-half-maximum
(FWHM) of 288 nm is first reported from ZnGa2O4: Ni2+ nano-spinels embedded GCs
with excellent transparency. A comparison is made of the NIR luminescence
properties of Ni2+ doped GCs containing ZnGa2O4, germanium-substituted ZnGa2O4
nano-spinels (Zn1+x Ga2-2x Ge x O4), and Zn2GeO4/Li2Ge4O9 composite nanocrystals
that are free of Ga3+. The results show that ZnGa2O4: Ni2+ GCs exhibit a
significantly enhanced NIR emission. The incorporation of the nucleating agent
TiO2 is favored in terms of the increased luminescence intensity and prolonged
lifetime. The possible causes for the enhancement effect are identified from the
crystal structure/defects viewpoint. The newly developed GCs incorporate good
reproducibility to allow for a tolerance of thermal treatment temperature and
hence hold great potential of fiberization via the recently proposed "melt-in
tube" method. They can be considered as promising candidates for broadband fiber
amplifiers.
PMID- 28496208
TI - Ethylenation of aldehydes to 3-propanal, propanol and propanoic acid derivatives.
AB - Methodology has been developed for the synthesis of 3-propanaldehydes through a
five-step process in 11-67% yield from aldehydes. Aldehydes were reacted with
Meldrum's acid through a Knoevenagel condensation to give materials that upon
reduction with sodium borohydride and subsequent hydrolysis decarboxylation
generated the corresponding 3-propanoic acid derivatives. The -propanoic acid
derivatives were reduced to give 3-propanol derivatives, which were readily
oxidised to target 3-propanal derivatives.
PMID- 28496209
TI - Single-cell pH imaging and detection for pH profiling and label-free rapid
identification of cancer-cells.
AB - Single-cell pH-sensing and accurate detection and label-free fast identification
of cancer-cells are two long-standing pursuits in cell and life science, as
intracellular pH plays a crucial role in many cellular events and fates, while
the latter is vital for early cancer theranostics. Numerous methods based on
functionalized nanoparticles and fluorescence probes have been developed for cell
pH-sensing, but are often hindered for single-cell studies by their main
drawbacks of complicated probe preparation and labeling, low sensitivity and poor
reproducibility. Here we report a simple and reliable method for single-cell pH
imaging and sensing by innovative combined use of UV-Vis microspectroscopy and
common pH indicators. Accurate and sensitive pH detection on single-cell or sub
cell level with good reproducibility is achieved by the method, which enables
facile single-cell pH profiling and label-free rapid identification of cancer
cells (due to distinguishable intracellular pH levels) for early cancer
diagnosis, and may open a new avenue for pH-related single-cell studies.
PMID- 28496210
TI - The caterpillar fungus, Ophiocordyceps sinensis, genome provides insights into
highland adaptation of fungal pathogenicity.
AB - To understand the potential genetic basis of highland adaptation of fungal
pathogenicity, we present here the ~116 Mb de novo assembled high-quality genome
of Ophiocordyceps sinensis endemic to the Qinghai-Tibetan Plateau. Compared with
other plain-dwelling fungi, we find about 3.4-fold inflation of the O. sinensis
genome due to a rapid amplification of long terminal repeat retrotransposons that
occurred ~38 million years ago in concert with the uplift of the plateau. We also
observe massive removal of thousands of genes related to the transport process
and energy metabolism. O. sinensis displays considerable lineage-specific
expansion of gene families functionally enriched in the adaptability of low
temperature of cold tolerance, fungal pathogenicity and specialized host
infection. We detect signals of positive selection for genes involved in
peroxidase and hypoxia to enable its highland adaptation. Resequencing and
analyzing 31 whole genomes of O. sinensis, representing nearly all of its
geographic range, exhibits latitude-based population divergence and nature
selection for population inhabitation towards higher altitudes on the Qinghai
Tibetan Plateau.
PMID- 28496211
TI - How to design a randomised controlled trial.
AB - This practical paper explains how to design an randomised controlled trial (RCT)
for those who have little prior knowledge of the topic. It covers the basics of
radomisation, statistical testing, sample size caluclations, bias and the role of
Clinical Trial Units.
PMID- 28496217
TI - Fear of the dentist.
AB - The oral health of individuals with dental phobia: a multivariate analysis of the
Adult Dental Health Survey, 2009.
PMID- 28496215
TI - Consent - an update.
AB - Following the judgement in Montgomery in March 2015 which brought the law of
consent up to speed with what the GDC 's ethical and professional guidance
expected registrants to do, this article looks at how other cases have
interpreted Montgomery subsequently and the impact and implications for dentists.
The importance of excellent communication is emphasised in order to provide
sufficient and relevant information to the particular patient you have sitting in
your dental chair.
PMID- 28496218
TI - Case report: Giant cell arteritis warning.
PMID- 28496219
TI - The Flipped Classroom for pre-clinical dental skills teaching - a reflective
commentary.
AB - A Flipped Classroom method for teaching of adult practical pre-clinical dental
skills was introduced to the BDS curriculum in Glasgow during the 2015/2016
academic session. This report provides a commentary of the first year of
employing this method - from the identification of the need to optimise teaching
resources, through the planning, implementation and development of the method,
with an early indication of performance.
PMID- 28496221
TI - Is the novelty wearing off?
AB - Investigation of the erosive potential of sour novelty sweets.
PMID- 28496220
TI - Using a situational judgement test for selection into dental core training: a
preliminary analysis.
AB - Objective and setting This paper describes the evaluation of a pilot situational
judgement test (SJT) for selection into UK Dental Core Training (DCT). The SJT's
psychometric properties, group differences based on gender and ethnicity, and
candidate reactions were assessed.Methods The SJT targets four non-academic
attributes important for success in DCT. Data were collected alongside live
selection processes from five Health Education England local teams in the UK (N =
386). Candidates completed the pilot SJT and an evaluation questionnaire to
examine their reactions to the test.Results SJT scores were relatively normally
distributed and showed acceptable levels of internal reliability (alpha = 0.68).
Difficulty level and partial correlations between scenarios and SJT total score
were in the expected ranges (64.61% to 90.03% and r = 0.06 to 0.41,
respectively). No group differences were found for gender, and group differences
between White and BME candidates were minimal. Most candidates perceived the SJT
as relevant to the target role, appropriate and fair.Conclusions This study
demonstrated the potential suitability of an SJT for use in DCT selection. Future
research should replicate these preliminary findings in other cohorts, and assess
the predictive validity of the SJT for predicting key training and practice-based
outcomes.
PMID- 28496222
TI - EFP launch European Gum Health Day 2017 in Spain.
PMID- 28496224
TI - Case report: Odontalgia and facial pain.
PMID- 28496225
TI - Altmetric analysis of 2015 dental literature: a cross sectional survey.
AB - Introduction To report and analyse Altmetric data of all dental articles and
journals in 2015.Methods To identify all 2015 dental articles, PubMed was
searched via Altmetric platform using the following query: ("2015/1/1"[PDAT]:
"2015/12/31"[PDAT]) AND jsubsetd[text] NOT 2016[PDAT] on November 12, 2016.
Altmetric data of all 2015 dental articles and journals were extracted and
analysed by Microsoft Office Excel 2016 using descriptive statistics, graphs and
trend-line analysis. To find the most important and influential Altmetric
factors, multi-layered perceptron artificial neural network was employed using
SPSS 22.Results A total of 14,884 dental articles published in 2015 using PubMed
database were found, from which 5,153 (34.62%) articles had an Altmetric score.
The mean Altmetric score was 2.94 +/- 9.2 (95% C.I:2.703.22). Mendeley readers
(73.19%), Twitter (21.48%), Facebook walls (3.67%), news outlets (0.69%) and
bloggers (0.57%) were the most popular Altmetric data resources. At journal
level, 147 dental journals with valid Altmetric data were included in the study.
The British Dental Journal had the first rank, followed by Journal of Dental
Research, Journal of Clinical Periodontology and Journal of the American Dental
Association. Sensitivity analysis showed news outlets, tweeters and scientific
bloggers were the most important and influential Altmetric data
resources.Discussion In comparison with all science subjects and medical and
health sciences, 2015 Altmetric scores in dentistry were very low. Uses of new
and emerging scholarly tools such as social media, scientific blogs and post
publication peer-review were not common in the dental science. This negligence
may be due to lack of knowledge and attitude. An Altmetric score is dynamic and
may fluctuate over time.
PMID- 28496226
TI - Oral cancer: Early/delayed diagnosis.
PMID- 28496227
TI - Who regulates the regulator?
PMID- 28496228
TI - Roy Storer.
PMID- 28496230
TI - Invasive cervical resorption and the oro-facial cleft patient: a review and case
series.
AB - Introduction Invasive cervical resorption (ICR) has an unknown aetiology, yet it
exhibits very aggressive behaviour compared with typical external root
resorption, posing a high risk of tooth loss.Aim To investigate the number of
patients at the Dublin Cleft Prosthodontic Department with an oro-facial cleft
who experienced ICR and to identify any possible aetiological factors.Materials
and method A retrospective investigation of all oro-facial cleft patients treated
at the Dublin Cleft Prosthodontic Department, St James's Hospital, Dublin. All
patients' clinical and radiological records were reviewed. Patients where tooth
loss became inevitable due to Class 4 ICR were analysed.Results From 588 oro
facial cleft patients, 14 (2.38%) patients with ICR were identified. Of these
eight (57%) were female and six (43%) were male. Mean age at diagnosis was 28
years (range = 16-49 years). Cleft type: six (42.1%) unilateral cleft lip and
palate, eight (57.9%) bilateral cleft lip and palate. Seventeen ICR affected
teeth in total, with eleven (65%) maxillary central incisors, two (12%) maxillary
lateral incisors, four (23%) maxillary canines, and one (7%) central, lateral and
canine affected. Some, (N = 10, 71.4%) presented with ICR resulting in immediate
tooth loss. Other patients (N = 4, 28.6%) developed ICR during or following
prosthodontic treatment at the Cleft Centre. Tooth loss for this cohort, though
not immediate, was inevitable. All had undergone fixed orthodontic appliance
treatment and twelve had received dento-alveolar bone grafts. A number (N = 7,
50%) had undergone osteotomy, two (14%) had received night guard vital dental
whitening and one had a history of trauma.Conclusions ICR, given its aggressive
nature and ill-understood aetiology, poses significant treatment challenges. The
most severe form of ICR (Class 4) leads inevitably to tooth loss. The slow
moderate progression of ICR may explain the late presentation found in this
study, reinforcing the importance of long-term follow-up of this special dental
care group.
PMID- 28496231
TI - Comparing the profile of child patients attending dental general anaesthesia and
conscious sedation services.
AB - Aims To compare the profile of paediatric patients receiving dental treatment
under general anaesthesia (GA) or conscious sedation (CS). A second aim was to
explore whether there is an overlap between the two patient groups.Design This
service evaluation study was based on sociodemographic and clinical data
extracted from clinical records of patients attending dental appointments for GA
or CS services at King's College Hospital. Sociodemographic and clinical
differences between GA and CS groups were explored using logistic regression
models.Results Data from 113 children (58 GA and 55 CS) were analysed. There were
differences between groups in terms of age and numbers of quadrants and teeth
treated, but not in terms of sex, ethnicity or deprivation scores. In the
adjusted model, older children and those having more teeth treated were more
likely to be in the GA than in the CS group. An overlap between the GA and CS
groups was found, with 50% of children aged four to nine years having two to four
teeth treated in both groups.Conclusion Age and number of teeth treated were the
main characteristics associated with receiving care under GA or CS. Some overlap
between children receiving dental treatment under GA or CS existed despite
demographic and clinical differences between both groups.
PMID- 28496232
TI - Mystery object: Denture drop.
PMID- 28496234
TI - Water fluoridation: It really is this simple.
PMID- 28496235
TI - Dentists fully support HPV jabs for boys.
PMID- 28496238
TI - OMFS: Dental fitness prior to cardiac surgery.
PMID- 28496239
TI - Dental practice: Loyal and caring staff.
PMID- 28496244
TI - Systematic review and meta-analysis of randomised controlled trials on the
effectiveness of school-based dental screening versus no screening on improving
oral health in children.
AB - No effect of school-based dental screening programmes on caries or dental
attendance.
PMID- 28496240
TI - Beyond ONJ - A review of the potential uses of bisphosphonates in dentistry.
AB - There is evidence, although limited, for beneficial effects of bisphophonates
(BPs) across multiple dental specialties. Within implant dentistry BP coatings
have been shown to significantly increase pull out forces and bone density in
animal models, and significantly increase implant stability whilst reducing
marginal bone loss in humans. Adjunctive topical and systemic application of BPs
during conventional periodontal treatment have shown significant improvements in
probing depth and clinical attachment level in various forms of periodontal
disease. Within orthodontics, BPs have been shown to significantly reduce root
resorption and have benefits with respect to anchorage maintenance. Case reports
have suggested the use of BPs in the management of diffuse sclerosing
osteomylitis. Whilst this review highlights these potential benefits and
acknowledges there are no reported cases of osteonecrosis of the jaw associated
with locally applied BP, there remains a paucity of human and long-term studies
exploring BPs in the context of significant clinical benefit. Further human
studies are required to understand the long-term clinical outcomes of these drugs
when used as primary therapeutic agents, or adjuncts to conventional treatment.
PMID- 28496246
TI - Harold Andreas Priestland.
PMID- 28496248
TI - Fluoride varnish: our only hope?
AB - Outcomes and costs of pre-school and school-based fluoride varnish pilots.
PMID- 28496250
TI - First Chinese student in Plymouth as part of dental partnership.
PMID- 28496251
TI - The management of cracked tooth syndrome in dental practice.
AB - Cracked tooth syndrome is a commonly encountered condition in dental practice
which frequently causes diagnostic and management challenges. This paper provides
an overview of the diagnosis of this condition and goes on to discuss current
short and long-term management strategies applicable to dental practitioners.
This paper also covers the diagnosis and management of this common condition and
aims to inform clinicians of the current thinking, as well as to provide an
overview of the techniques commonly used in managing cracked tooth syndrome.
PMID- 28496253
TI - Survey on the use of CAD-CAM technology by UK and Irish dental technicians.
AB - Statement of the problem Digital workflows (CAD/CAM) have been introduced in
dentistry during recent years. No published information exists on dental
technicians' use and reporting of this technology.Purpose The aim of this cross
sectional survey was to identify the extent digital technology has infiltrated
the workplace and to investigate the factors affecting the use of CAD-CAM
technology by dental laboratory technicians within Ireland and the UK.Materials
and methods A web-based questionnaire was composed (Opinio, Object Planet Inc.
Oslo, Norway) and distributed to UK and Irish dental technicians. Answers to all
questions were anonymous and grouped such that general information was gathered
initially, followed by branching of the survey into two sections depending on
whether or not the respondent worked with CAD-CAM technology. Results were
compiled and statistical analysis (Fisher's Exact test, SPSS, IBM, Armonk, New
York, USA) was performed in order to investigate any correlation between various
demographic variables and the answers provided.Results The survey was distributed
to 760 UK technicians and 77 Irish technicians. The total number of completed
surveys was 105, which yielded a total response rate of 14%. Most technicians
reported using some form of CAD/CAM aspect in the workflow, and this was more
significant for technicians working in large laboratories. Most training received
was company-led. Large laboratories were also significantly correlated with less
outsourcing of CAD/CAM work and a change in dental material use leading to the
increase of zirconia and the decrease of noble alloys. Dental technicians did not
report any significant change in working relationships and staffing as a result
of CAD/CAM incorporation. High initial investment cost was the most common reason
quoted from non-users, along with the lack of such technology in their working
environment.
PMID- 28496255
TI - Enhanced skills in periodontology: evaluation of a pilot scheme for general
dental practitioners and dental care professionals in London.
AB - Background The need for periodontal management is great and increasing; thus, the
oral and dental workforce should be suitably equipped to deliver contemporary
care. Health Education London developed a training scheme to extend the skills of
dentists and dental care professionals (DCPs).Aim To examine the feasibility of
assessing a skill-mix initiative established to enhance skills in clinical
periodontology involving the views of patients, clinicians and key stakeholders,
together with clinical and patient outcomes in London.Methods This mixed methods
feasibility and pilot study involved four parallel elements: a postal
questionnaire survey of patients; analysis of clinical logbooks; self-completion
questionnaire survey of clinicians; and semi-structured interviews of key
stakeholders, including clinicians.Results Twelve of the 19 clinicians
participated in the evaluation, returning completed questionnaires (63%) and
providing access to log diaries and patients. Periodontal data from 42 log-diary
cases (1,103 teeth) revealed significant improvement in clinical outcomes (P =
0.001 for all). Eighty-four percent (N = 99) of the 142 patients returning a
questionnaire reported improved dental health; however, responses from hospital
patients greatly exceeded those from dental practice. Interviews (N = 22)
provided evidence that the programme contributed to professional healthcare
across four key domains: 'service', 'quality care', 'professional' and
'educational'. Clinicians, while supportive of the concept, raised concerns
regarding the mismatch of their expectations and its educational and service
outcomes.Discussion The findings suggest that it is feasible to deliver and
evaluate inter-professional extended skills training for dentists and dental care
professionals, and this may be evaluated using mixed methods to examine outcomes
including clinical log diaries, patient questionnaires and stakeholder
interviews. This inter-professional course represents a positive development for
patient care using the expertise of different members of the dental team;
however, its formal integration to the health and educational sectors require
further consideration.
PMID- 28496257
TI - Case report: Osteonecrosis as a complication of GA.
PMID- 28496258
TI - A systematic review of the survival and complication rates of inlayretained fixed
dental prostheses.
AB - Difficult to make any clear recommendations, as many combinations of mechanical
and biological characteristics may contribute to the survival of such
restorations.
PMID- 28496261
TI - Making Students' Thinking Visible During Active Learning.
PMID- 28496260
TI - Overexpression of a cytochrome P450 and a UDP-glycosyltransferase is associated
with imidacloprid resistance in the Colorado potato beetle, Leptinotarsa
decemlineata.
AB - Current control of insect pests relies on chemical insecticides, however,
insecticide resistance development by pests is a growing concern in pest
management. The main mechanisms for insecticide resistance typically involve
elevated activity of detoxifying enzymes and xenobiotic transporters that break
down and excrete insecticide molecules. In this study, we investigated the
molecular mechanisms of imidacloprid resistance in the Colorado potato beetle,
Leptinotarsa decemlineata (Say) (Coleoptera: Chrysomelidae), an insect pest
notorious for its capacity to develop insecticide resistance rapidly. We compared
the transcriptome profiles of imidacloprid-resistant and sensitive beetle strains
and identified 102 differentially expressed transcripts encoding detoxifying
enzymes and xenobiotic transporters. Of these, 74 were up-regulated and 28 were
down-regulated in the resistant strain. We then used RNA interference to knock
down the transcript levels of seven up-regulated genes in the resistant beetles.
Ingestion of double-stranded RNA successfully knocked down the expression of the
genes for three cytochrome P450s (CYP6BQ15, CYP4Q3 and CYP4Q7), one ATP binding
cassette (ABC) transporter (ABC-G), one esterase (EST1), and two UDP
glycosyltransferases (UGT1 and UGT2). Further, we demonstrated that silencing of
CYP4Q3 and UGT2 significantly increased susceptibility of resistant beetles to
imidacloprid, indicating that overexpression of these two genes contributes to
imidacloprid resistance in this resistant strain.
PMID- 28496262
TI - Recruiting the Right Students.
PMID- 28496263
TI - Lessons From a Recovering Department Chair.
PMID- 28496264
TI - Current and Future Opportunities and Challenges in Continuing Pharmacy Education.
AB - The Accreditation Council for Pharmacy Education (ACPE) convened a consensus
seeking invitational conference on October 29-30, 2015, in Chicago, Ill. ACPE's
desire to have stakeholder guidance on its role in the future of continuing
pharmacy education and continuing professional development led to the convening
of the conference. The purpose of this article is to summarize the proceedings of
the conference, including the recommendations from the stakeholders.
PMID- 28496265
TI - A Pharmacotherapy Capstone Course to Target Student Learning and Programmatic
Curricular Assessment.
AB - Objective. To describe how a pharmacotherapy capstone course was used for student
learning and programmatic curricular assessment. Design. A pharmacotherapy
capstone course was included in the University of Colorado curriculum for 13
years from 2002 through 2014. This 9-credit hour course was the last course prior
to Advanced Pharmacy Practice Experiences (APPEs). Students were held accountable
for prior learning using complex patient cases and other activities that are seen
in APPEs. Application of knowledge, skills, and critical thinking were integrated
in this course using exclusively active learning methodologies. Students were
expected to actively participate and learn independently, from peers and through
self-assessment. Assessment. Evidence of student learning was demonstrated based
on student performance on written and verbal evaluations analyzed from 2012 to
2014. Survey and self-evaluation data indicated that students learned within the
course. An increase in student confidence in critical thinking, problem-solving,
decision making, and lifelong learning was also seen during APPEs. Student
performance in this course prompted changes to prerequisite courses and guided
development of a renewed curriculum. Conclusion. The University of Colorado
pharmacotherapy capstone course prepared students for the rigor of APPEs,
provided insight that facilitated improvements in prerequisite courses, and was a
nexus for the development of a renewed curriculum, which includes a new clinical
capstone course.
PMID- 28496267
TI - Performance and Perceptions of Student Teams Created and Stratified Based on
Academic Abilities.
AB - Objective. To compare student performance, elements of peer evaluation and
satisfaction of teams created according to students' course entrance grade point
average (GPA). Methods. Two course sections were divided into teams of four to
five students utilizing Comprehensive Assessment of Team Member Effectiveness
(CATME) software. Results. Of 336 students enrolled, 324 consented to
participation. Weekly team quiz averages were 99.1% (higher GPA), 97.2% (lower
GPA), 97.7% (mixed GPA). Weekly individual quiz averages were 87.2% (higher GPA),
83.3% (lower GPA), 85.2% (mixed GPA). Students with same GPA performed similarly
individually independent of team assignment. Satisfaction ranged from 4.52
(higher GPA), 4.73 (lower GPA), 4.53 (mixed GPA). Conclusion. Academically
stronger students in mixed GPA teams appeared to be at a slight disadvantage
compared to similar students in higher GPA teams. There was no difference in team
performance for academically weaker students in lower GPA versus mixed GPA teams.
Team satisfaction was higher in lower GPA teams.
PMID- 28496266
TI - Computer-Assisted Decision Support for Student Admissions Based on Their
Predicted Academic Performance.
AB - Objective. To develop predictive computational models forecasting the academic
performance of students in the didactic-rich portion of a doctor of pharmacy
(PharmD) curriculum as admission-assisting tools. Methods. All PharmD candidates
over three admission cycles were divided into two groups: those who completed the
PharmD program with a GPA >= 3; and the remaining candidates. Random Forest
machine learning technique was used to develop a binary classification model
based on 11 pre-admission parameters. Results. Robust and externally predictive
models were developed that had particularly high overall accuracy of 77% for
candidates with high or low academic performance. These multivariate models were
highly accurate in predicting these groups to those obtained using undergraduate
GPA and composite PCAT scores only. Conclusion. The models developed in this
study can be used to improve the admission process as preliminary filters and
thus quickly identify candidates who are likely to be successful in the PharmD
curriculum.
PMID- 28496268
TI - Effect of a Dedicated Pharmacy Student Summer Research Program on Publication
Rate.
AB - Objectives. This study investigated the impact of an optional 12-week summer
research program on the publication outcomes and satisfaction with the required
research projects of doctor of pharmacy (PharmD) students at the Skaggs School of
Pharmacy and Pharmaceutical Sciences (SSPPS) at the University of California San
Diego. Methods. PubMed and Google searches provided student publications, and
satisfaction surveys submitted by students provided their perceptions of the
research project value. Results. Of the studied cohort, the 130 students who
fulfilled the requirement through the optional summer research program provided
61 full-text manuscripts and 113 abstracts. The 305 students who chose the
standard pathway provided 35 full-text manuscripts and 34 abstracts. Students in
both pathways agreed or strongly agreed that the research project was a valuable
experience. Conclusions. The 12-week intensive summer research program improved
the publication rate of pharmacy students and provided a high overall
satisfaction with this independent learning experience.
PMID- 28496269
TI - Best Practices for Use of Blended Learning.
AB - Objective. To determine instructional best practice recommendations for use of
blended learning from the students' perspective. Methods. Three focus groups were
created, one for each of the first three years at a school of pharmacy. The focus
group discussions were audio recorded and transcribed for content analysis.
Results. Ten instructional best practices were identified from the focus groups:
setting the stage, consistency when team teaching, timeliness in posting
materials, time on task, accountability for online activities, use of structured
active learning, instructor use of feedback on student preparation, incorporation
of student feedback into the course, short reviews of online material during
class, and ensuring technologies are user friendly. Conclusion. Instructors using
blended learning should consider incorporating these best practices into their
course design and management. More evaluation is needed to see if implementation
of these practices affects student performance.
PMID- 28496270
TI - Exercise as a Stress Coping Mechanism in a Pharmacy Student Population.
AB - Objective. To assess the coping mechanisms used by pharmacy students and their
relationship to perceived stress. Methods. Data were gathered utilizing the
Perceived Stress Scale (PSS10) and Brief COPE with the additional coping
mechanisms of exercise and use of prescribed medications. Results. A survey that
was sent to 368 students had an 81% response rate. Perceived stress was
significantly higher than standard populations, but consistent with other
pharmacy student populations. The most frequently reported coping mechanisms were
the adaptive strategies of active coping, acceptance and planning. Maladaptive
strategies of behavioral disengagement, venting and self-blame were significantly
associated with higher perceived stress scores and the new addition of an
exercise coping mechanism significantly associated with lower perceived stress
scores. Use of prescribed medications was not significantly associated with
perceived stress levels. Conclusion. Inclusion of exercise as a coping mechanism
may be beneficial in similar populations.
PMID- 28496271
TI - An Analysis of Quality Improvement Education at US Colleges of Pharmacy.
AB - Objective. Analyze quality improvement (QI) education across US pharmacy
programs. Methods. This was a two stage cross-sectional study that inspected each
accredited school website for published QI curriculum or related content, and e
mailed a questionnaire to each school asking about QI curriculum or content. T
test and chi square were used for analysis with an alpha a priori set at .05.
Results. Sixty responses (47% response rate) revealed the least-covered QI
topics: quality dashboards /sentinel systems (30%); six-sigma or other QI
methodologies (45%); safety and quality measures (57%); Medicare Star measures
and payment incentives (58%); and how to implement changes to improve quality
(60%). More private institutions covered Adverse Drug Events than public
institutions and required a dedicated QI class; however, required QI projects
were more often reported by public institutions. Conclusion. Despite the need for
pharmacists to understand QI, it is not covered well in school curricula.
PMID- 28496272
TI - Evaluation of a Longitudinal Advanced Pharmacy Practice Experience.
AB - Objective. To describe satisfaction and career path of students who participated
in the longitudinal advanced pharmacy practice experience (APPE). Methods. A 3
part survey was administered to students enrolled between January 1, 2010, and
December 31, 2013. The sections of the survey evaluated respondents' baseline
characteristics, satisfaction, and career path. Results. Majority of the
respondents had a GPA above 3.0 (91%), pharmacy school honors (84%), work
experience in retail (16%) or multiple pharmacy sites (38%), and were members of
at least one professional organization (76%). Sixty-nine percent reported that
the program exceeded their expectations. Strengths included practice site
consistency, rotation diversity, preceptors, presentations, and collaboration
with health care professionals. Students gained approximately 76 hours of
additional clinical experience, compared to if they completed rotations at
individual sites. After graduation, more than half of the respondents accepted a
pharmacy practice residency (67%). Conclusion. The results of this study support
the need for APPE programs that prepare students to deliver advanced patient
care, while providing them with professional development.
PMID- 28496273
TI - Predictive Relationships Between Students' Evaluation Ratings and Course
Satisfaction.
AB - Objective. To assess the reliability and validity of course evaluation data.
Methods. A correlation study was conducted using archival data from pharmacy
student course evaluations. Bivariate relationships between eight course-rating
items and overall rating item and the extent to which course type, level, and
grade point average moderated these relationships were analyzed. Results.
Significant bivariate relationships were found between the eight course
evaluation rating variables and the overall course rating variable. Pharmacy
practice course type significantly moderated the relationship between all
predictor and criterion variables. Conclusion. Pharmacy school administrators
should consider individual course evaluation item ratings when making decisions
regarding course offerings or faculty promotion and tenure.
PMID- 28496274
TI - Student Self-Assessment and Faculty Assessment of Performance in an
Interprofessional Error Disclosure Simulation Training Program.
AB - Objectives. To conduct a prospective evaluation for effectiveness of an error
disclosure assessment tool and video recordings to enhance student learning and
metacognitive skills while assessing the IPEC competencies. Design. The
instruments for assessing performance (planning, communication, process, and team
dynamics) in interprofessional error disclosure were developed. Student self
assessment of performance before and after viewing the recordings of their
encounters were obtained. Faculty used a similar instrument to conduct real-time
assessments. An instrument to assess achievement of the Interprofessional
Education Collaborative (IPEC) core competencies was developed. Qualitative data
was reviewed to determine student and faculty perceptions of the simulation.
Assessment. The interprofessional simulation training involved a total of 233
students (50 dental, 109 nursing and 74 pharmacy). Use of video recordings made a
significant difference in student self-assessment for communication and process
categories of error disclosure. No differences in student self-assessments were
noted among the different professions. There were differences among the family
member affects for planning and communication for both pre-video and post-video
data. There were significant differences between student self-assessment and
faculty assessment for all paired comparisons, except communication in student
post-video self-assessment. Students' perceptions of achievement of the IPEC core
competencies were positive. Conclusion. The use of assessment instruments and
video recordings may have enhanced students' metacognitive skills for assessing
performance in interprofessional error disclosure. The simulation training was
effective in enhancing perceptions on achievement of IPEC core competencies. This
enhanced assessment process appeared to enhance learning about the skills needed
for interprofessional error disclosure.
PMID- 28496275
TI - Qualitative Analysis of Student Perceptions Comparing Team-based Learning and
Traditional Lecture in a Pharmacotherapeutics Course.
AB - Objective. To qualitatively compare students' attitudes and perceptions regarding
team-based learning (TBL) and lecture. Design. Students were exposed to TBL and
lecture in an elective pharmacotherapeutics course in a randomized, prospective,
cross-over design. After completing the course, students provided their attitudes
and perceptions through a written self-reflection and narrative questions on the
end-of-course evaluation. Student responses were reviewed using a grounded theory
coding method. Assessment. Students' responses yielded five major themes: impact
of TBL on learning, perceptions about TBL learning methods, changes in approaches
to learning, building skills for professional practice, and enduring challenges.
Overall, students report TBL enhances their learning of course content (knowledge
and application), teamwork skills, and lifelong learning skills. Conclusion.
Students' attitudes and perceptions support TBL as a viable pedagogy for teaching
pharmacotherapeutics.
PMID- 28496276
TI - Using Patient Case Video Vignettes to Improve Students' Understanding of Cross
cultural Communication.
AB - Objective. To develop, implement, and assess whether simulated patient case
videos improve students' understanding of and attitudes toward cross-cultural
communication in health care. Design. Third-year pharmacy students (N=159) in a
health care communications course participated in a one-hour lecture and two-hour
workshop on the topic of cross-cultural communication. Three simulated pharmacist
patient case vignettes highlighting cross-cultural communication barriers, the
role of active listening, appropriate use of medical interpreters, and useful
models to overcome communication barriers were viewed and discussed in groups of
20 students during the workshop. Assessment. A pre-lecture and post-workshop
assessed the effect on students' understanding of and attitudes toward cross
cultural communication. Understanding of cross-cultural communication concepts
increased significantly, as did comfort level with providing cross-cultural care.
Conclusion. Use of simulated patient case videos in conjunction with an
interactive workshop improved pharmacy students' understanding of and comfort
level with cross-cultural communication skills and can be useful tools for
cultural competency training in the curriculum.
PMID- 28496277
TI - A Framework for Integrating Biosimilars Into the Didactic Core Requirements of a
Doctor of Pharmacy Curriculum.
AB - Biologic drugs approved via the abbreviated United States biosimilar approval
pathway are anticipated to improve access to medications by addressing increasing
health care expenditures. Surveys of health care practitioners indicate that
there is inadequate knowledge and understanding about biosimilars; this must be
addressed to ensure safe and effective use of this new category of products.
Concepts of biosimilar development, manufacturing, regulation, naming, formulary,
and inventory considerations, as well as patient and provider education should be
included within the doctor of pharmacy (PharmD) curriculum as preparation for
clinical practice. Based on these considerations, we propose that PharmD
graduates be required to have knowledge in the following domains regarding
biologics and biosimilars: legal definition, development and regulation, state
pharmacy practice laws, and pharmacy practice management. We link these general
biosimilar concepts to the Accreditation Council for Pharmacy Education (ACPE)
Standards 2016 and Center for the Advancement of Pharmacy Education (CAPE)
Outcomes 2013, and provide example classroom learning objectives, in-class
activities, and assessments to guide implementation.
PMID- 28496278
TI - Point/Counterpoint: Are Outstanding Leaders Born or Made?
AB - The question of whether outstanding leaders are born or made has been debated for
years. There are numerous examples of historical figures that came naturally to
leadership, while others developed their leadership skills through tenacity and
experience. To understand leadership, both nature (the genetic component) and
nurture (the environmental influences) must be considered. This article
represents the work of two Academic Leadership Fellows Program groups who debated
each position at the 2016 American Association of Colleges of Pharmacy (AACP)
Interim Meeting in Tampa, Fla., in February 2016.
PMID- 28496279
TI - Professional Attire Dress Codes for PharmD Programs Should Not Be Mandatory.
PMID- 28496280
TI - Expanding Dress Code Requirements in the Doctor of Pharmacy Program.
PMID- 28496281
TI - Comparison of Herbarium Label Data and Published Medicinal Use: Herbaria as an
Underutilized Source of Ethnobotanical Information.
AB - The use of herbarium specimens as vouchers to support ethnobotanical surveys is
well established. However, herbaria may be underutilized resources for
ethnobotanical research that depends on the analysis of large datasets compiled
across multiple sites. Here, we compare two medicinal use datasets, one sourced
from published papers and the other from online herbaria to determine whether
herbarium and published data are comparable and to what extent herbarium
specimens add new data and fill gaps in our knowledge of geographical extent of
plant use. Using Brazilian legumes as a case study, we compiled 1400 use reports
from 105 publications and 15 Brazilian herbaria. Of the 319 species in 107 genera
with cited medicinal uses, 165 (51%) were recorded only in the literature and 55
(17%) only on herbarium labels. Mode of application, plant part used, or
therapeutic use was less often documented by herbarium specimen labels (17% with
information) than publications (70%). However, medicinal use of 21 of the 128
species known from only one report in the literature was substantiated from
independently collected herbarium specimens, and 58 new therapeutic applications,
25 new plant parts, and 16 new modes of application were added for species known
from the literature. Thus, when literature reports are few or information-poor,
herbarium data can both validate and augment these reports. Herbarium data can
also provide insights into the history and geographical extent of use that are
not captured in publications.
PMID- 28496282
TI - A comparison of race-related pain stereotypes held by White and Black
individuals.
AB - Pain judgments are the basis for pain management. The purpose of this study was
to assess Black and White participants' race-related pain stereotypes.
Undergraduates (n=551) rated the pain sensitivity and willingness to report pain
for the typical Black person, White person, and themselves. Participants,
regardless of race, rated the typical White person as being more pain sensitive
and more willing to report pain than the typical Black person. White participants
rated themselves as less sensitive and less willing to report pain than same-race
peers; however, Black participants rated themselves as more pain sensitive and
more willing to report pain than same-race peers. These findings highlight
similarities and differences in racial stereotypic pain beliefs held by Black and
White individuals.
PMID- 28496283
TI - The 9/11 Dust Cloud and Pregnancy Outcomes: A Reconsideration.
AB - The events of 9/11 released a million tons of toxic dust into lower Manhattan, an
unparalleled environmental disaster. It is puzzling then that the literature has
shown little effect of fetal exposure to the dust. However, inference is
complicated by pre-existing differences between the affected mothers and other
NYC mothers as well as heterogeneity in effects on boys and girls. Using all
births in utero on 9/11 in NYC and comparing them to their siblings, we show that
residence in the affected area increased prematurity and low birth weight,
especially for boys.
PMID- 28496284
TI - Using Hydrazine to Link Ferrocene with Re(CO)3: A Modular Approach.
AB - Acetyl ferrocene and diacetyl ferrocene both readily react with an excess of
hydrazine to afford the corresponding hydrazone compounds. These compounds can
then be linked to Re(CO)3 via a metal-mediated Schiff base reaction, resulting in
a series of ferrocene-Re(CO)3 conjugates with different stoichiometries.
Conjugates with 1:1, 1:2, and 2:1 ferrocene: Re(CO)3 ratios can be produced via
this "modular" type synthesis approach. Several examples of these conjugates were
structurally characterized, and their spectroscopic, electrochemical, and
spectroelectrochemical behaviors were investigated. The electronic structures of
these compounds were also probed using DFT and TDDFT calculations.
PMID- 28496285
TI - Partial identification in the statistical matching problem.
AB - The statistical matching problem involves the integration of multiple datasets
where some variables are not observed jointly. This missing data pattern leaves
most statistical models unidentifiable. Statistical inference is still possible
when operating under the framework of partially identified models, where the goal
is to bound the parameters rather than to estimate them precisely. In many
matching problems, developing feasible bounds on the parameters is equivalent to
finding the set of positive-definite completions of a partially specified
covariance matrix. Existing methods for characterising the set of possible
completions do not extend to high-dimensional problems. A Gibbs sampler to draw
from the set of possible completions is proposed. The variation in the observed
samples gives an estimate of the feasible region of the parameters. The Gibbs
sampler extends easily to high-dimensional statistical matching problems.
PMID- 28496286
TI - Mental Health Interventions for Children in Foster Care: A Systematic Review.
AB - Children in foster care have high rates of adverse childhood experiences and are
at risk for mental health problems. These problems can be difficult to
ameliorate, creating a need for rigorous intervention research. Previous research
suggests that intervening with children in foster care can be challenging for
several reasons, including the severity and complexity of their mental health
problems, and challenges engaging this often transitory population in mental
health services. The goal of this article was to systematically review the
intervention research that has been conducted with children in foster care, and
to identify future research directions. This review was conducted on mental
health interventions for children, ages 0 to 12, in foster care, using ERIC,
CINAHL, PsycINFO, PubMed, ProQuest's Dissertation and Theses Database, Social
Services Abstracts, and Social Work Abstracts. It was restricted to interventions
that are at least "possibly efficacious" (i.e., supported by evidence from at
least one randomized controlled trial). Studies were evaluated for risk of bias.
Ten interventions were identified, with diverse outcomes, including mental health
and physiological. Six interventions were developed for children in foster care.
Interventions not developed for children in foster care were typically adapted to
the foster context. Most interventions have yet to be rigorously evaluated in
community-based settings with children in foster care. Little research has been
conducted on child and family engagement within these interventions, and there is
a need for more research on moderators of intervention outcomes and subgroups
that benefit most from these interventions. In addition, there is not consensus
regarding how to adapt interventions to this population. Future research should
focus on developing and testing more interventions with this population,
rigorously evaluating their effectiveness in community-based settings,
determining necessary adaptations, and identifying which interventions work best
for whom.
PMID- 28496287
TI - A systems theoretic approach to analysis and control of mammalian circadian
dynamics.
AB - The mammalian circadian clock is a complex multi-scale, multivariable biological
control system. In the past two decades, methods from systems engineering have
led to numerous insights into the architecture and functionality of this system.
In this review, we examine the mammalian circadian system through a process
systems lens. We present a mathematical framework for examining the cellular
circadian oscillator, and show recent extensions for understanding population
scale dynamics. We provide an overview of the routes by which the circadian
system can be systemically manipulated, and present in silico proof of concept
results for phase resetting of the clock via model predictive control.
PMID- 28496288
TI - Mesopredator behavioral response to olfactory signals of an apex predator.
AB - Olfactory signals constitute an important mechanism in interspecific
interactions, but little is known regarding their role in communication between
predator species. We analyzed the behavioral responses of a mesopredator, the red
fox (Vulpes vulpes), to an olfactory cue (scat) of an apex predator, the lynx
(Lynx lynx) in Bialowieza Primeval Forest, Poland, using video camera traps. Red
fox visited sites with scats more often than expected and the duration of their
visits was longer at scat sites than at control sites (no scat added). Vigilant
behavior, sniffing and scent marking (including over-marking) occurred more often
at scat sites compared to control sites, where foxes mainly passed by. Vigilance
was most pronounced during the first days of the recordings. Red fox behavior was
also influenced by foxes previously visiting scat sites. They sniffed and scent
marked (multiple over-marking) more frequently when the lynx scat had been over
marked previously by red fox. Fox visits to lynx scats may be seen as a trade-off
between obtaining information on a potential food source (prey killed by lynx)
and the potential risk of predation by an apex predator.
PMID- 28496289
TI - What if Reading is Easy but Unimportant? How Students' Patterns of Affirming and
Undermining Motivation for Reading Information Texts Predict Different Reading
Outcomes.
AB - Many affirming and undermining motivational constructs affect students as they
read information texts, but few researchers have explored how these motivations
are patterned within students. In this study we used cluster analysis to classify
middle school students (n = 1,134) based on their patterns of self-efficacy,
perceived difficulty, value, and devalue for reading school information texts. We
then compared how the patterns predicted students' language arts grades, science
information text comprehension, and dedication to reading school information
texts. We found and validated a four-cluster solution. One cluster included a
pattern of high affirming and low undermining motivations, and another included
low affirming and high undermining motivations. Students with these patterns
earned the highest and lowest scores, respectively, on all outcomes. A third
pattern showed high self-efficacy/low difficulty with low value/high devalue, and
a fourth showed moderate levels of all four motivational constructs. Students
with the high efficacy and devalue pattern showed high information text
comprehension but relatively low dedication. Students with the moderate pattern
showed high dedication but low initial information text comprehension. Students
with these two patterns earned similar grades. We discuss the implications of our
findings for motivation theories and for school instruction that involves
information text reading.
PMID- 28496290
TI - Quantitative analysis of amphiphilic N-alkyloxypyridinecarboximidamide by liquid
chromatography-tandem mass spectrometry.
AB - LC-MS/MS method to determine hydrophobic N-alkyloxy substituted amidines: N-(2
ethylhexyloxy)pyridine-2-carboximidamide, N-(2-ethylhexyloxy)pyridine-3
carboximidamide, N-(2-ethylhexyloxy)pyridine-4-carboximidamide, N-decyloxy
pyridine-2-carboximidamide, N-decyloxypyridine-3-carboximidamide and N
decyloxypyridine-4-carboximidamide was developed and validated in terms of
linearity, precision and accuracy. The developed method was successfully applied
to monitor and control the synthesis process. The experimental data points
indicated that the straight chain alkyl bromide reacted most rapidly than
branched alkyl bromide and the enhancement of the reaction efficiency strongly
depended on reaction temperature.
PMID- 28496291
TI - Family Functioning and Predictors of Runaway Behavior Among At-Risk Youth.
AB - PURPOSE: Adolescent runaway behavior is associated with a host of negative
outcomes in young adulthood. Therefore, it is important to understand the factors
that predict running away in youth. METHODS: Longitudinal data from 111 at-risk
families were used to identify proximal predictors of runaway behavior over a 12
week period. On average, youth were 14.96 years old, and 45% were female. Ten
percent of youth ran away during the 12-week follow-up period. RESULTS: In
bivariate analyses, running away was predicted by poorer youth- and parent-rated
family functioning, past runaway behavior, and other problem behaviors (e.g.,
substance use, delinquency), but not poorer perceived academic functioning.
Results of a hierarchical logistic regression revealed a relationship between
youth-rated family functioning and runaway behavior. However, this effect became
non-significant after accounting for past runaway behavior and other problem
behaviors, both of which remained significant predictors in the multivariable
model. CONCLUSION: These findings suggest that youth who run away may be engaged
in a more pervasive pattern of problematic behavior, and that screening and
prevention programs need to address the cycle of adolescent defiant behavior
associated with running away. Recommendations for clinical practice with this at
risk population are discussed.
PMID- 28496292
TI - Speaker verification based on the fusion of speech acoustics and inverted
articulatory signals.
AB - We propose a practical, feature-level and score-level fusion approach by
combining acoustic and estimated articulatory information for both text
independent and text dependent speaker verification. From a practical point of
view, we study how to improve speaker verification performance by combining
dynamic articulatory information with the conventional acoustic features. On text
independent speaker verification, we find that concatenating articulatory
features obtained from measured speech production data with conventional Mel
frequency cepstral coefficients (MFCCs) improves the performance dramatically.
However, since directly measuring articulatory data is not feasible in many real
world applications, we also experiment with estimated articulatory features
obtained through acoustic-to-articulatory inversion. We explore both feature
level and score level fusion methods and find that the overall system performance
is significantly enhanced even with estimated articulatory features. Such a
performance boost could be due to the inter-speaker variation information
embedded in the estimated articulatory features. Since the dynamics of
articulation contain important information, we included inverted articulatory
trajectories in text dependent speaker verification. We demonstrate that the
articulatory constraints introduced by inverted articulatory features help to
reject wrong password trials and improve the performance after score level
fusion. We evaluate the proposed methods on the X-ray Microbeam database and the
RSR 2015 database, respectively, for the aforementioned two tasks. Experimental
results show that we achieve more than 15% relative equal error rate reduction
for both speaker verification tasks.
PMID- 28496293
TI - The Effect of Dopaminergic Medication on Joint Kinematics during Haptic Movements
in Individuals with Parkinson's Disease.
AB - This study examined whether altered joint angular motion during haptic
exploration could account for a decline in haptic sensitivity in individuals with
PD by analyzing joint position data during haptic exploration of a curved
contour. Each participant's hand was passively moved by a robotic arm along the
edges of a virtual box (5 cm * 15 cm) with a curved left wall. After each trial,
participants indicated whether the contour was curved or straight. Visual,
auditory, and tactile cues were occluded, and an electrogoniometer recorded
shoulder and elbow joint angles during each trial. The PD group in the OFF state
had a higher mean detection threshold (4.67 m-1) than the control group (3.06 m
1). Individuals with PD in the OFF state also had a significantly greater
magnitude of shoulder abduction than those in the ON state (p = 0.003) and a
smaller magnitude of elbow flexion than those in the ON state or compared to the
control group (both p < 0.001). These findings suggest that individuals with PD
employ joint configurations that may contribute to haptic insensitivity. Dopamine
replacement therapy improved joint configurations during haptic exploration in
patients with PD, suggesting a role for dopaminergic dysfunction in PD-related
haptic insensitivity.
PMID- 28496294
TI - Policing 'Vancouver's Mental Health Crisis': A Critical Discourse Analysis.
AB - In Canada and other western nations there has been an unprecedented expansion of
criminal justice systems and a well documented increase of contact between people
with mental illness and the police. Canadian police, especially in Vancouver,
British Columbia, have been increasingly at the forefront of discourse and
regulation specific to mental health. Drawing on critical discourse analysis,
this paper to explores this claim through a case study of four Vancouver Police
Department (VPD) policy reports on "Vancouver's mental health crisis" from 2008
2013, which include recommendations for action. Analyzed is the VPD's role in
framing issues of mental health in one urban space. This study is the first
analysis to critically examine the VPD reports on mental health in Vancouver,
B.C. The reports reproduce negative discourses about deinstitutionalization,
mental illness and dangerousness that may contribute to further stigma and
discrimination of persons with mental illness. Policing reports are widely drawn
upon, thus critical analyses are particularly significant for policy makers and
public health professionals in and outside of Canada.
PMID- 28496295
TI - Convergence analysis of an iterative algorithm for the extended regularized
nonconvex variational inequalities.
AB - In this paper, we suggest and analyze a new system of extended regularized
nonconvex variational inequalities and prove the equivalence between the
aforesaid system and a fixed point problem. We introduce a new perturbed
projection iterative algorithm with mixed errors to find the solution of the
system of extended regularized nonconvex variational inequalities. Furthermore,
under moderate assumptions, we research the convergence analysis of the suggested
iterative algorithm.
PMID- 28496297
TI - SemiContour: A Semi-supervised Learning Approach for Contour Detection.
AB - Supervised contour detection methods usually require many labeled training images
to obtain satisfactory performance. However, a large set of annotated data might
be unavailable or extremely labor intensive. In this paper, we investigate the
usage of semi-supervised learning (SSL) to obtain competitive detection accuracy
with very limited training data (three labeled images). Specifically, we propose
a semi-supervised structured ensemble learning approach for contour detection
built on structured random forests (SRF). To allow SRF to be applicable to
unlabeled data, we present an effective sparse representation approach to capture
inherent structure in image patches by finding a compact and discriminative low
dimensional subspace representation in an unsupervised manner, enabling the
incorporation of abundant unlabeled patches with their estimated structured
labels to help SRF perform better node splitting. We re-examine the role of
sparsity and propose a novel and fast sparse coding algorithm to boost the
overall learning efficiency. To the best of our knowledge, this is the first
attempt to apply SSL for contour detection. Extensive experiments on the BSDS500
segmentation dataset and the NYU Depth dataset demonstrate the superiority of the
proposed method.
PMID- 28496296
TI - A Systematic Review of the Literature on Parenting of Young Children with Visual
Impairments and the Adaptions for Video-Feedback Intervention to Promote Positive
Parenting (VIPP).
AB - Secure parent-child attachment may help children to overcome the challenges of
growing up with a visual or visual-and-intellectual impairment. A large
literature exists that provides a blueprint for interventions that promote
parental sensitivity and secure attachment. The Video-feedback Intervention to
promote Positive Parenting (VIPP) is based on that blueprint. While it has been
adapted to several specific at risk populations, children with visual impairment
may require additional adjustments. This study aimed to identify the themes that
should be addressed in adapting VIPP and similar interventions. A Delphi
consultation was conducted with 13 professionals in the field of visual
impairment to select the themes for relationship-focused intervention. These
themes informed a systematic literature search. Interaction, intersubjectivity,
joint attention, exploration, play and specific behavior were the themes
mentioned in the Delphi-group. Paired with visual impairment or vision disorders,
infants or young children (and their parents) the search yielded 74 articles,
making the six themes for intervention adaptation more specific and concrete. The
rich literature on six visual impairment specific themes was dominated by the
themes interaction, intersubjectivity, and joint attention. These themes need to
be addressed in adapting intervention programs developed for other populations,
such as VIPP which currently focuses on higher order constructs of sensitivity
and attachment.
PMID- 28496298
TI - Feature-based Analysis of Large-scale Spatio-Temporal Sensor Data on Hybrid
Architectures.
AB - Analysis of large sensor datasets for structural and functional features has
applications in many domains, including weather and climate modeling,
characterization of subsurface reservoirs, and biomedicine. The vast amount of
data obtained from state-of-the-art sensors and the computational cost of
analysis operations create a barrier to such analyses. In this paper, we describe
middleware system support to take advantage of large clusters of hybrid CPU-GPU
nodes to address the data and compute-intensive requirements of feature-based
analyses in large spatio-temporal datasets.
PMID- 28496299
TI - Response of eyes with age-related macular degeneration to anti-VEGF drugs and
implications for therapy planning.
AB - PURPOSE: To evaluate the response to and dependence on aflibercept or ranibizumab
in patients with age-related macular degeneration (AMD). METHODS: We
retrospectively reviewed AMD patients who received induction therapy with
aflibercept or ranibizumab for the following parameters: whether complete
resolution of the retinal fluid ("good response") was achieved and whether
recurrence was observed within 3 months ("dependent") after the induction
treatment. With aflibercept treatment, treatment-naive eyes with a good
response/non-dependence were recommended a pro re nata regimen, and other eyes
were recommended a proactive bimonthly regimen, followed by monitoring of visual
acuity (VA) for 12 months. The measured values of the groups were compared using
one-way analysis of variance with Tukey's test to evaluate the difference between
baseline and postinjection VA. RESULTS: Among the treatment-naive eyes, 76% had a
good response to aflibercept and 37% of these were aflibercept-dependent, while
58% had a good response to ranibizumab but 51% of these were ranibizumab
dependent. Among the eyes that converted from ranibizumab treatment, 92% of the
good responders to ranibizumab with dependence and 76% of the poor responders on
ranibizumab had a good response to aflibercept. With aflibercept treatment, the
mean VA of treatment-naive patients was significantly better than the baseline VA
over 12 months (P<0.001), and the VA of the converted group improved
significantly with proactive treatment and the improvement was continuously
maintained from 6 to 12 months. CONCLUSION: The evaluation of response to and
dependence on anti-vascular endothelial growth factor therapies in AMD was useful
and practical in managing therapeutic protocols to obtain a good VA.
PMID- 28496300
TI - Prospective evaluation of intense pulsed light and meibomian gland expression
efficacy on relieving signs and symptoms of dry eye disease due to meibomian
gland dysfunction.
AB - PURPOSE: The aim of this study was to estimate the efficacy of intense pulsed
light (IPL), followed by meibomian gland expression (MGX), for reducing the
number and severity of signs and symptoms of dry eye disease (DED) secondary to
meibomian gland dysfunction (MGD). PATIENTS AND METHODS: In a prospective study
conducted in two sites, 40 subjects (80 eyes) with moderate to severe MGD were
enrolled. Major inclusion criteria consisted of at least two of the following
measures being compatible with DED in both eyes: tear breakup time (TBUT),
meibomian gland score (MGS), corneal fluorescein staining (CFS), Standard Patient
Evaluation of Eye Dryness (SPEED) questionnaire, and tear film osmolarity (TFO).
Enrolled patients underwent four treatment sessions, 3 weeks apart. Each
treatment included the administration of 10-15 pulses of IPL on the cheeks and
nose, followed by MGX of the upper and lower eyelids. TBUT, MGS, CFS, SPEED, TFO,
and lipid layer thickness (LLT) were measured at baseline (BL) and at 9, 12, and
15 weeks after BL. RESULTS: Due to different staining methods used for TBUT
measurements, TBUT and CFS were analyzed separately for each site. From BL to the
final follow-up, the number of signs compatible with DED decreased from 3.3+/-0.1
to 1.4+/-0.1. TBUT improved by +93% (n=38; P<0.0001) and +425% (n=42; P<0.0001)
for sites 1 and 2, respectively. SPEED, MGS, and CFS improved by -55% (n=80;
P<0.0001), -36% (n=80; P<0.0001), and -58% (n=38; P<0.0001), respectively. In 20
eyes with abnormally elevated TFO at BL, TFO improved by -7% (n=20; P<0.005). LLT
did not change (n=38; P=0.88). CONCLUSION: In subjects with moderate to severe
MGD, IPL combined with MGX reduced the number and severity of symptoms and signs
of DED. Except for LLT, all examined outcome measures significantly improved
after 15 weeks. These results support the efficacy of IPL + MGX in relieving both
signs and symptoms of DED secondary to MGD.
PMID- 28496301
TI - Short-term outcomes in patients with branch retinal vein occlusion who received
intravitreal aflibercept with or without intravitreal ranibizumab.
AB - PURPOSE: The purpose of this study was to determine the short-term outcomes for
patients who received intravitreal aflibercept (IVA) with or without intravitreal
ranibizumab (IVR) for macular edema (ME) due to branch retinal vein occlusion
(BRVO). PATIENTS AND METHODS: Patients received IVA for ME due to BRVO. Patients
who initially received IVA were defined as the treatment-naive group and those
who were switched from IVR to IVA after ME recurrence were defined as the
switching group. Patient outcomes were examined at 1 week and 1 month
postinjection. RESULTS: Both groups comprised 27 eyes from 27 patients. There was
a significant decrease in central macular thickness (CMT) at 1 week and 1 month
postinjection in both groups. There was also a significant improvement in best
corrected visual acuity (BCVA) at 1 week and 1 month postinjection in the
treatment-naive group and 1 month in the switching group. Younger age was
associated with a good BCVA at 1 month postinjection in the switching group, and
the absence of epiretinal membrane was associated with a reduction in CMT at 1
month postinjection in the switching group. CONCLUSION: IVA is temporarily
effective for treating ME due to BRVO regardless of a history of IVR use.
PMID- 28496302
TI - Goldmann tonometer error correcting prism: clinical evaluation.
AB - PURPOSE: Clinically evaluate a modified applanating surface Goldmann tonometer
prism designed to substantially negate errors due to patient variability in
biomechanics. METHODS: A modified Goldmann prism with a correcting applanation
tonometry surface (CATS) was mathematically optimized to minimize the intraocular
pressure (IOP) measurement error due to patient variability in corneal thickness,
stiffness, curvature, and tear film adhesion force. A comparative clinical study
of 109 eyes measured IOP with CATS and Goldmann prisms. The IOP measurement
differences between the CATS and Goldmann prisms were correlated to corneal
thickness, hysteresis, and curvature. RESULTS: The CATS tonometer prism in
correcting for Goldmann central corneal thickness (CCT) error demonstrated a
reduction to <+/-2 mmHg in 97% of a standard CCT population. This compares to
only 54% with CCT error <+/-2 mmHg using the Goldmann prism. Equal reductions of
~50% in errors due to corneal rigidity and curvature were also demonstrated.
CONCLUSION: The results validate the CATS prism's improved accuracy and expected
reduced sensitivity to Goldmann errors without IOP bias as predicted by
mathematical modeling. The CATS replacement for the Goldmann prism does not
change Goldmann measurement technique or interpretation.
PMID- 28496303
TI - Development of a potent invigorator of immune responses endowed with both
preventive and therapeutic properties.
AB - This article reviews briefly the making of an immunoprophylactic-cum
immunotherapeutic vaccine against leprosy. The vaccine is based on cultivable,
heat-killed atypical mycobacteria, whose gene sequence is now known. It has been
named Mycobacterium indicus pranii. It has received the approval of the Drug
Controller General of India and the US Food and Drug Administration. Besides
leprosy, M. indicus pranii has found utility in the treatment of category II
("difficult to treat") tuberculosis. It also heals ugly anogenital warts. It has
preventive and therapeutic action against SP2/O myelomas. It is proving to be a
potent adjuvant for enhancing antibody titers of a recombinant vaccine against
human chorionic gonadotropin, with the potential of preventing pregnancy without
derangement of ovulation and menstrual regularity in sexually active women.
PMID- 28496304
TI - Evaluation of the antitumor activity of NOV202, a novel microtubule targeting and
vascular disrupting agent.
AB - PURPOSE: Overall, ~65% of patients diagnosed with advanced ovarian cancer (OC)
will relapse after primary surgery and adjuvant first-line platinum- and taxane
based chemotherapy. Significant improvements in the treatment of OC are expected
from the development of novel compounds having combined cytotoxic and
antiangiogenic properties that make them effective on refractory tumors. METHODS:
Permeability of NOV202 was determined with Caco-2 monolayer assay. The compound's
pharmacokinetic profile and plasma:brain distribution were assessed in male
C57Bl/6 mice. The compound's impacts on tubulin, microtubules and cell cycle were
investigated by using in vitro tubulin polymerization assay, cell-based
immunofluorescence and live cell microscopy. The IC50 concentrations of NOV202
were assessed in a panel of eight cancer cell lines. Impact of the compound on
vascular tube formation was determined using the StemKit and Chick
chorioallantoic membrane assays. The in vivo efficacy of the compound was
analyzed with an OC xenograft mouse model. RESULTS: NOV202 was found to suppress
cancer cell proliferation at low nanomolar concentrations (IC50 2.3-12.0 nM) and
showed equal efficacy between OC cell line A2780 (IC50 2.4 nM) and its multidrug
resistant subline A2780/Adr (IC50 2.3 nM). Mechanistically, NOV202 targeted
tubulin polymerization in vitro in a dose-dependent manner and in cells induced
an M phase arrest. In vivo, NOV202 caused a dose-dependent reduction of tumor
mass in an A2780 xenograft model, which at the highest dose (40 mg/kg) was
comparable to the effect of paclitaxel (24 mg/kg). Interestingly, NOV202
exhibited vascular disrupting properties that were similar to the effects of
Combretastatin A4. CONCLUSION: NOV202 is a novel tubulin and vascular targeting
agent that shows strong anticancer efficacy in cells and OC xenograft models. The
finding that the compound induced significantly more cell death in Pgp/MDR1
overexpressing OC cells compared to vincristine and paclitaxel warrants further
development of the compound as a new therapy for OC patients with treatment
refractory tumors and/or relapsing disease.
PMID- 28496306
TI - Erratum: Combined letrozole and clomiphene versus letrozole and clomiphene alone
in infertile patients with polycystic ovary syndrome [Erratum].
AB - [This corrects the article on p. 1427 in vol. 7.][This corrects the article on p.
1427 in vol. 7.].
PMID- 28496305
TI - Methanol leaf extract of Actinodaphne sesquipedalis (Lauraceae) enhances gastric
defense against ethanol-induced ulcer in rats.
AB - Actinodaphne sesquipedalis Hook. F. Var. Glabra (Kochummen), also known as
"Medang payung" by the Malay people, belongs to the Lauraceae family. In this
study, methanol leaf extract of A. sesquipedalis was investigated for their acute
toxicity and gastroprotective effects to reduce ulcers in rat stomachs induced by
ethanol. The rats were assigned to one of five groups: normal group (group 1),
ulcer group (group 2), control positive drug group (group 3) and two experimental
groups treated with 150 mg/kg (group 4) and 300 mg/kg (group 5) of leaf extract.
The rats were sacrificed an hour after pretreatment with extracts, and their
stomach homogenates and tissues were collected for further evaluation.
Macroscopic and histological analyses showed that gastric ulcers in rats
pretreated with the extract were significantly reduced to an extent that it
allowed leukocytes penetration of the gastric walls compared with the ulcer
group. In addition, an ulcer inhibition rate of >70% was detected in rats treated
with both doses of A. sesquipedalis extract, showing a notable protection of
gastric layer. Severe destruction of gastric mucosa was prevented with a high
production of mucus and pH gastric contents in both omeprazole-treated and
extract-treated groups. Meanwhile, an increase in glycoprotein uptake was
observed in pretreated rats through accumulation of magenta color in Periodic
Acid Schiff staining assay. Analysis of gastric homogenate from pretreated rats
showed a reduction of malondialdehyde and elevation of nitric oxide, glutathione,
prostaglandin E2, superoxide dismutase and protein concentration levels in
comparison with group 2. Suppression of apoptosis in gastric tissues by
upregulation of Hsp70 protein and downregulation of Bax protein was also observed
in rats pretreated with extract. Consistent results of a reduction of gastric
ulcer and the protection of gastric wall were obtained for rats pretreated with
A. sesquipedalis extract, which showed its prominent gastroprotective potential
in rats' stomach against ethanol-induced ulcer.
PMID- 28496307
TI - Developing selective histone deacetylases (HDACs) inhibitors through ebselen and
analogs.
AB - Histone deacetylases (HDACs) are key regulators of gene expression in cells and
have been investigated as important therapeutic targets for cancer and other
diseases. Different subtypes of HDACs appear to play disparate roles in the cells
and are associated with specific diseases. Therefore, substantial effort has been
made to develop subtype-selective HDAC inhibitors. In an effort to discover
existing scaffolds with HDAC inhibitory activity, we screened a drug library
approved by the US Food and Drug Administration and a National Institutes of
Health Clinical Collection compound library in HDAC enzymatic assays. Ebselen, a
clinical safe compound, was identified as a weak inhibitor of several HDACs,
including HDAC1, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, and HDAC9 with half
maximal inhibitory concentrations approximately single digit of uM. Two ebselen
analogs, ebselen oxide and ebsulfur (a diselenide analog of ebselen), also
inhibited these HDACs, however with improved potencies on HDAC8. Benzisothiazol,
the core structure of ebsulfur, specifically inhibited HDAC6 at a single digit of
uM but had no inhibition on other HDACs. Further efforts on structure-activity
relationship based on the core structure of ebsulfur led to the discovery of a
novel class of potent and selective HDAC6 inhibitors with RBC-2008 as the lead
compound with single-digit nM potency. This class of histone deacetylase
inhibitor features a novel pharmacophore with an ebsulfur scaffold selectively
targeting HDAC6. Consistent with its inhibition on HDAC6, RBC-2008 significantly
increased the acetylation levels of alpha-tubulin in PC-3 cells. Furthermore,
treatment with these compounds led to cell death of multiple tumor cell lines in
a dose-dependent manner. These results demonstrated that ebselen and ebsulfur
analogs are inhibitors of HDACs, supporting further preclinical development of
this class of compounds for potential therapeutic applications.
PMID- 28496308
TI - Atorvastatin, a double weapon in osteoporosis treatment: an experimental and
clinical study.
AB - OBJECTIVE: The aim of this study was to evaluate the effect of atorvastatin on
the bone formation and resorption markers in ovariectomized rats (experimental
study), and to study its effect on the bone mineral density (BMD) in
postmenopausal osteoporotic women (clinical study). MATERIALS AND METHODS: The
study involved experimental and clinical aspects. In the experimental aspect, 42
female Wistar rats were divided into five groups: Group I (n=6; sham-operated),
Group II (n=6; 1 mL of carboxymethyl cellulose [CMC] was administered orally),
Group III (n=6; 20 mg/kg orally of atorvastatin was administered), Group IV
(n=12; untreated ovariectomized [OVX] rats and served as a model of osteoporosis
[OP]) and Group V (n=12; 20 mg/kg orally of atorvastatin was administered to
ovariectomized rats). After 4 weeks, serum acid phosphatase, alkaline
phosphatase, osteocalcin, total calcium and inorganic phosphorus were assessed.
Then, 3 um thickness lumbar and femur sections were examined using a light
microscope to assess cortical thickness, trabecular area, numbers of osteoblasts
and osteoclasts. In the clinical aspect, 85 post-menopausal osteoporotic females
with recently detected hyperlipidemia participated in the study. Atorvastatin 40
mg/day, calcium carbonate 500 mg/day and vitamin D 800 international units were
given to all patients for a period of 18 months. BMD was measured at the start
and at the end of the study by dual-energy X-ray absorptiometry (DEXA). RESULTS:
In the experiment aspect, the biomarkers of bone remodeling were notably elevated
in the OVX group. Administration of atorvastatin produced a significant decrease
in the level of these bone metabolic markers. Atorvastatin significantly
ameliorates osteoporotic changes induced by ovariectomy. In the clinical aspect,
after 18 months the DEXA showed improvement in the T-score for the three measured
zones; however, these changes were statistically significant only in the femoral
neck area. CONCLUSION: Atorvastatin was able to decrease the rate of bone
metabolism and increase osteogenic activity. It has dual mode of action; both
anabolic and antiresorptive effect on bone. This lipophilic statin member may act
as a double weapon drug.
PMID- 28496309
TI - Effect of electromagnetic fields and antioxidants on the trace element content of
rat teeth.
AB - The purpose of this study was to examine the possible effect of extremely low
frequency electromagnetic fields (ELF-EMFs), from a high-voltage source, on rat
teeth in terms of changes in trace elements (TEs) and the effect of antioxidants
(melatonin [MLT] and Ganoderma lucidum [GL]) in counteracting these effects. We
used adult male Wistar albino rats with a mean weight of 250-300 g and divided
the rats into eight groups. The groups were subjected to an ELF-EMF that was
applied with a high-voltage line for 8 hours/day for 26 days (Groups I, II, and
III) or 52 days (Groups V, VI, and VII). Groups IV and VIII were the 26- and 52
day control/sham groups, respectively. Groups II and VI were treated with GL, and
Groups III and VII were treated with MLT. MLT and GL were administered daily
based on the weight of the animals and appropriate standards. At the end of the
study, the rats were euthanized, and their anterior teeth were extracted. The
teeth were preserved in pure water before evaluating the major TEs. At the end of
the study, TE concentrations (in mg/kg) were assessed in the control and test
groups. Compared with Group V, statistically significant differences in the
concentrations of zinc (Zn) and strontium (Sr) were found for Group VII (ELF-EMF
+ MLT) (P<0.05). Therefore, ELF-EMF exposure can change the content of certain
TEs in teeth and, after administering MLT and GL, the values of some of the TEs
return to normal.
PMID- 28496310
TI - Patient satisfaction with fixed-combination bimatoprost/timolol ophthalmic
solution: a survey study in patients with glaucoma in China.
AB - BACKGROUND: Poor adherence to treatment is a problem in glaucoma, and patient
dissatisfaction with topical glaucoma medication is a barrier to adherence. The
objective of this study was to evaluate glaucoma patients' satisfaction with
fixed-combination bimatoprost/timolol ophthalmic solution (BTFC). METHODS: This
observational, multicenter study was conducted in China in adults with glaucoma
treated with BTFC for 1-3 months. Five hundred patients answered a questionnaire
concerning their demographic characteristics, history of glaucoma and topical
glaucoma treatment, and use of BTFC. The primary endpoint was patient
satisfaction with BTFC assessed on a 10-point scale (1= very dissatisfied, 10=
very satisfied). RESULTS: Patients received BTFC alone (65%) or with other
treatments (35%), most commonly a carbonic anhydrase inhibitor. Most patients
(87%) used BTFC as a replacement for other medication, usually a beta-blocker or
prostaglandin analog; 13% received BTFC as add-on treatment. Key reasons for
initiating BTFC therapy were poor efficacy of previous treatment (72% of
patients) and side effects of previous treatment (32% of patients). Most patients
agreed or very much agreed that BTFC provided better control of intraocular
pressure (85% of patients), had a simpler administration (87% of patients), and
was associated with better tolerance and comfort (82% of patients) compared with
their previous treatment. Mean satisfaction scores were significantly higher for
BTFC than for previous treatments among all patients (7.8 versus 6.0; P<0.0001)
and within patient subgroups based on demographic characteristics, pattern of
BTFC use, and previous treatment. CONCLUSION: Patients were highly satisfied with
BTFC used alone or concomitantly with another topical medication. Patients
previously treated with a beta-blocker, prostaglandin analog, carbonic anhydrase
inhibitor, alpha-adrenergic agonist, or combination of two medications were more
satisfied with BTFC than with their previous treatment. Most reported that
intraocular pressure control, tolerability, and ease of administration improved
with BTFC.
PMID- 28496311
TI - Letter regarding the article "The impact of hypomagnesemia on erectile
dysfunction in elderly, non-diabetic, stage 3 and 4 chronic kidney disease
patients: a prospective cross-sectional study".
PMID- 28496312
TI - Body mass index is associated with type 2 diabetes mellitus in Chinese elderly.
AB - BACKGROUND: There is limited information on the association between metabolic
syndrome components including body mass index (BMI) and type 2 diabetes mellitus
in elderly Chinese population. Therefore, we investigated whether components of
metabolic syndrome are associated with type 2 diabetes mellitus in elderly.
METHODS: A total of 479 hospitalized patients (aged 65-95 years) with recently
diagnosed type 2 diabetes mellitus were studied retrospectively in a cross
sectional study and compared with 183 subjects with prediabetes and 62 subjects
without glucose metabolism abnormalities. RESULTS: BMI (24.69+/-3.59 versus
23.92+/-3.08 and 23.56+/-3.25 kg/m2), blood pressure, cholesterol, triglyceride,
liver enzymes and prevalence of fatty liver were higher in patients with type 2
diabetes mellitus as compared with elderly subjects with prediabetes or normal
glucose metabolism separately (all P<0.05). Multivariable regression analysis
showed that BMI was associated positively with insulin resistance and inversely
with insulin sensitivity in type 2 diabetes mellitus group (all P<0.05).
CONCLUSION: Higher BMI was associated with increased insulin resistance and
decreased insulin sensitivity in elderly Asian population with type 2 diabetes
mellitus.
PMID- 28496313
TI - Relationships of pancreatic beta-cell function with microalbuminuria and
glomerular filtration rate in middle-aged and elderly population without type 2
diabetes mellitus: a Chinese community-based analysis.
AB - BACKGROUND: Relationships of pancreatic beta-cell function abnormality with
microalbuminuria (MA) and glomerular filtration rate (GFR) may differ by age,
ethnicity and accompanied diseases. Previous studies were generally conducted in
Western adult patients with type 2 diabetes mellitus (T2DM), and it is uncertain
whether pancreatic beta-cell function is associated with MA and GFR in Chinese
community-dwelling middle-aged and elderly population without T2DM. We therefore
examined the relationships of pancreatic beta-cell function with two indices of
renal damage, MA and GFR, in Chinese community-dwelling middle-aged and elderly
population without T2DM. METHODS: This analysis focused on 380 Beijing residents
older than 45 years who were free of T2DM and completed the evaluation of
pancreatic beta-cell function. RESULTS: Median age was 67 (49-80) years. Levels
of triglyceride, diastolic blood pressure and homeostasis model assessment-beta
(HOMA-beta) index were positively related to urine microalbumin (P<0.05 for all).
Age, low-density lipoprotein cholesterol levels and HOMA-beta index were
inversely correlated with GFR, while high-density lipoprotein cholesterol levels
were positively correlated with GFR (P<0.05 for all). In all three adjustment
models, there was a significant positive association between HOMA-beta index and
MA; subjects with higher beta-cell function had higher odds of MA (P<0.05 for
all). There was no association between HOMA-beta index and GFR <60 mL/min/1.73 m2
in any model (P>0.05 for all). CONCLUSION: Modeling the pancreatic beta-cell
function with different adjusted variables provided the same conclusion of
association with MA; beta-cell function was positively associated with MA.
Additionally, there was a specific difference in the adjusted associations of
pancreatic beta-cell function with MA and GFR <60 mL/min/1.73 m2; beta-cell
function was not independently associated with GFR <60 mL/min/1.73 m2. This
result indicated that abnormal pancreatic beta-cell function plays an important
role in the development of MA.
PMID- 28496314
TI - Treatment of lung disease in alpha-1 antitrypsin deficiency: a systematic review.
AB - BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a rare genetic condition
predisposing individuals to chronic obstructive pulmonary disease (COPD). The
treatment is generally extrapolated from COPD unrelated to AATD; however, most
COPD trials exclude AATD patients; thus, this study sought to systematically
review AATD-specific literature to assist evidence-based patient management.
METHODS: Standard review methodology was used with meta-analysis and narrative
synthesis (PROSPERO-CRD42015019354). Eligible studies were those of any treatment
used in severe AATD. Randomized controlled trials (RCTs) were the primary focus;
however, case series and uncontrolled studies were eligible. All studies had >=10
participants receiving treatment or usual care, with baseline and follow-up data
(>3 months). Risk of bias was assessed appropriately according to study
methodology. RESULTS: In all, 7,296 studies were retrieved from searches; 52
trials with 5,632 participants met the inclusion criteria, of which 26 studies
involved alpha-1 antitrypsin augmentation and 17 concerned surgical treatments
(largely transplantation). Studies were grouped into four management themes: COPD
medical, COPD surgical, AATD specific, and other treatments. Computed tomography
(CT) density, forced expiratory volume in 1 s, diffusing capacity of the lungs
for carbon monoxide, health status, and exacerbation rates were frequently used
as outcomes. Meta-analyses were only possible for RCTs of intravenous
augmentation, which slowed progression of emphysema measured by CT density
change, 0.79 g/L/year versus placebo (P=0.002), and associated with a small
increase in exacerbations 0.29/year (P=0.02). Mortality following lung transplant
was comparable between AATD- and non-AATD-related COPD. Surgical reduction of
lung volume demonstrated inferior outcomes compared with non-AATD-related
emphysema. CONCLUSION: Intravenous augmentation remains the only disease-specific
therapy in AATD and there is evidence that this slows decline in emphysema
determined by CT density. There is paucity of data around other treatments in
AATD. Treatments for usual COPD may not be as efficacious in AATD, and further
studies may be required for this disease group.
PMID- 28496315
TI - Hydrogen coadministration slows the development of COPD-like lung disease in a
cigarette smoke-induced rat model.
AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive
pulmonary disease caused by harmful gases or particles. Recent studies have shown
that 2% hydrogen or hydrogen water is effective in the treatment and prevention
of a variety of diseases. This study investigated the beneficial effects and the
possible mechanisms of different hydrogen concentrations on COPD. METHODS: A rat
COPD model was established through smoke exposure methods, and inhalation of
different concentrations of hydrogen was used as the intervention. The daily
condition of rats and the weight changes were observed; lung function and right
ventricular hypertrophy index were assessed. Also, white blood cells were
assessed in bronchoalveolar lavage fluid. Pathologic changes in the lung tissue
were analyzed using light microscopy and electron microscopy; cardiovascular
structure and pulmonary arterial pressure changes in rats were observed using
ultrasonography. Tumor necrosis factor alpha, interleukin (IL)-6, IL-17, IL-23,
matrix metalloproteinase-12, tissue inhibitor of metalloproteinase-1, caspase-3,
caspase-8 protein, and mRNA levels in the lung tissue were determined using
immunohistochemistry, Western blot, and real-time polymerase chain reaction.
RESULTS: The results showed that hydrogen inhalation significantly reduced the
number of inflammatory cells in the bronchoalveolar lavage fluid, and the mRNA
and protein expression levels of tumor necrosis factor alpha, IL-6, IL-17, IL-23,
matrix metalloproteinase-12, caspase-3, and caspase-8, but increased the tissue
inhibitor of metalloproteinase-1 expression. Furthermore, hydrogen inhalation
ameliorated lung pathology, lung function, and cardiovascular function and
reduced the right ventricular hypertrophy index. Inhalation of 22% and 41.6%
hydrogen showed better outcome than inhalation of 2% hydrogen. CONCLUSION: These
results suggest that hydrogen inhalation slows the development of COPD-like lung
disease in a cigarette smoke-induced rat model. Higher concentrations of hydrogen
may represent a more effective way for the rat model.
PMID- 28496316
TI - The effect of indacaterol/glycopyrronium versus tiotropium or
salmeterol/fluticasone on the prevention of clinically important deterioration in
COPD.
AB - BACKGROUND: Endpoints that evaluate deterioration rather than improvement of
disease may have clinical utility in COPD. In this analysis, we compared the
effects of different maintenance treatments on the prevention of clinically
important deterioration (CID) in moderate-to-severe COPD patients. METHODS: Data
were analyzed from three 26-week studies comparing indacaterol/glycopyrronium
(IND/GLY) with tiotropium (TIO) or salmeterol/fluticasone (SFC). Two definitions
of CID were used; each was a composite of three outcome measures typically
associated with COPD. Definition 1 (D1) comprised a >=100 mL decrease in forced
expiratory volume in 1 second (FEV1), a >=4-unit increase in St George's
Respiratory Questionnaire, and a moderate-to-severe COPD exacerbation. In
Definition 2 (D2), a >=1-unit decrease in transition dyspnea index replaced FEV1.
RESULTS: Using D1, IND/GLY significantly reduced the risk of first or sustained
CID versus either TIO (hazard ratio 0.72 [0.61, 0.86], P=0.0003 and 0.73 [0.61,
0.89], P=0.001) or SFC (0.67 [0.57, 0.80] and 0.63 [0.52, 0.77], both P<0.0001).
With D2, IND/GLY significantly reduced the risk of first, but not sustained, CID
versus TIO (0.80 [0.64 to 0.99], P=0.0359 and 0.85 [0.66, 1.10], P=0.2208) and
both first and sustained CID versus SFC (0.73 [0.61, 0.88], P=0.001 and 0.72
[0.58, 0.90], P=0.0036). CONCLUSION: These data confirm the utility of the CID
endpoint as a means of monitoring COPD worsening in patients with moderate-to
severe COPD. Using the CID measure, we demonstrated that dual bronchodilation
with IND/GLY significantly reduced the risk of CID versus either long-acting
muscarinic antagonist or long-acting beta2-agonist/inhaled corticosteroid
treatment, providing further evidence for the benefit of dual bronchodilation in
this patient population.
PMID- 28496318
TI - Pri-microRNA-124 rs531564 polymorphism minor allele increases the risk of
pulmonary artery hypertension by abnormally enhancing proliferation of pulmonary
artery smooth muscle cells.
AB - MicroRNA-124 (miR-124) has been reported to be downregulated in the cells exposed
to hypoxia, which was confirmed in our study. We then used online microRNA target
prediction tools to identify GRB2, SMAD5, and JAG1 as the candidate target genes
of miR-124, and we next validated GRB2 as a direct gene by using luciferase
reporter system. We also established the regulatory relationship between miR-124
and GRB2 by showing the negative linear relationship between GRB2 and miR-124
expression. Furthermore, we investigated the miR-124 and GRB2 expression levels
of different genotypes including CC (n=30), GC (n=18), and GG (n=4), which
supported the hypothesis that the presence of minor allele (C) of rs531564
polymorphism compromised the expression of miR-124. Meanwhile, we also conducted
real-time polymerase chain reaction and Western blot analysis to study the
expression of GRB2 among different genotypes or pulmonary artery smooth muscle
cells (PASMCs) treated with miR-124 mimics, GRB2 small interfering RNA, and miR
124 inhibitors, respectively, and found that introduction of miR-124 or GRB2
small interfering RNA could reduce the expression of GRB2 and inhibit the
proliferation of PASMCs, while miR-124 upregulated the expression of GRB2 and
promoted the proliferation of PASMCs. A total of 412 COPD patients with PAH
(n=182) or without PAH (n=230) were recruited in this study, and more individuals
carrying at least one minor allele of rs531564 were found in the COPD patients
with PAH than in those without PAH (odds ratio: 0.61, 95% confidence interval:
0.41-0.91; P=0.166). In conclusion, the presence of rs531564 minor allele may
increase the risk of PAH in COPD by reducing miR-124 expression, increasing GRB2
expression, and promoting the proliferation of PASMCs.
PMID- 28496317
TI - Is periodontitis a comorbidity of COPD or can associations be explained by shared
risk factors/behaviors?
AB - COPD is recognized as having a series of comorbidities potentially related to
common inflammatory processes. Periodontitis is one of the most common human
inflammatory diseases and has previously been associated with COPD in numerous
observational studies. As periodontitis and COPD are both chronic, progressive
conditions characterized by neutrophilic inflammation with subsequent proteolytic
destruction of connective tissue, it has been proposed that they share common
pathophysiological processes. The mechanisms proposed to link COPD and
periodontitis include mechanical aspiration of oral contents into the respiratory
tree, overspill of locally produced inflammatory mediators into the systemic
circulation or oral or lung-derived bacteremia activating an acute-phase response
and also reactive oxygen species (ROS) and cytokine release by systemic
neutrophils at distant sites. Studies of systemic neutrophils in COPD and chronic
periodontitis describe altered cellular functions that would predispose to
inflammation and tissue destruction both in the lung and in the mouth, again
potentially connecting these conditions. However, COPD and periodontitis also
share risk factors such as age, chronic tobacco smoke exposure, and social
deprivation that are not always considered in observational and interventional
studies. Furthermore, studies reporting associations have often utilized
differing definitions of both COPD and periodontitis. This article reviews the
current available evidence supporting the hypothesis that COPD and inflammatory
periodontal disease (periodontitis) could be pathologically associated, including
a review of shared inflammatory mechanisms. It highlights the potential
limitations of previous studies, in particular, the lack of uniformly applied
case definitions for both COPD and periodontitis and poor recognition of shared
risk factors. Understanding associations between these conditions may inform why
patients with COPD suffer such a burden of comorbid illness and new therapeutic
strategies for both the diseases. However, further research is needed to clarify
factors that may be directly causal as opposed to confounding relationships.
PMID- 28496319
TI - In vivo toxicologic study of larger silica nanoparticles in mice.
AB - Silica nanoparticles (SiNPs) are being studied and used for medical purposes. As
nanotechnology grows rapidly, its biosafety and toxicity have frequently raised
concerns. However, diverse results have been reported about the safety of SiNPs;
several studies reported that smaller particles might exhibit toxic effects to
some cell lines, and larger particles of 100 nm were reported to be genotoxic to
the cocultured cells. Here, we investigated the in vivo toxicity of SiNPs of 150
nm in various dosages via intravenous administration in mice. The mice were
observed for 14 days before blood examination and histopathological assay. All
the mice survived and behaved normally after the administration of nanoparticles.
No significant weight change was noted. Blood examinations showed no definite
systemic dysfunction of organ systems. Histopathological studies of vital organs
confirmed no SiNP-related adverse effects. We concluded that 150 nm SiNPs were
biocompatible and safe for in vivo use in mice.
PMID- 28496320
TI - Induction of mitophagy-mediated antitumor activity with folate-appended methyl
beta-cyclodextrin.
AB - Mitophagy is the specific autophagic elimination system of mitochondria, which
regulates cellular survival via the removal of damaged mitochondria. Recently, we
revealed that folate-appended methyl-beta-cyclodextrin (FA-M-beta-CyD) provides
selective antitumor activity in folate receptor-alpha (FR-alpha)-expressing cells
by the induction of autophagy. In this study, to gain insight into the detailed
mechanism of this antitumor activity, we focused on the induction of mitophagy by
the treatment of FR-alpha-expressing tumor cells with FA-M-beta-CyD. In contrast
to methyl-beta-cyclodextrin, FA-M-beta-CyD entered KB cells, human epithelial
cells from a fatal cervical carcinoma (FR-alpha (+)) through FR-alpha-mediated
endocytosis. The transmembrane potential of isolated mitochondria after treatment
with FA-M-beta-CyD was significantly elevated. In addition, FA-M-beta-CyD lowered
adenosine triphosphate (ATP) production and promoted reactive oxygen species
production in KB cells (FR-alpha (+)). Importantly, FA-M-beta-CyD enhanced light
chain 3 (LC3) conversion (LC3-I to LC3-II) in KB cells (FR-alpha (+)) and induced
PTEN-induced putative kinase 1 (PINK1) protein expression, which is involved in
the induction of mitophagy. Furthermore, FA-M-beta-CyD had potent antitumor
activity in BALB/c nu/nu mice xenografted with KB cells (FR-alpha (+)) without
any significant side effects. Taken together, these findings demonstrate that the
autophagic cell death elicited by FA-M-beta-CyD could be associated with
mitophagy induced by an impaired mitochondrial function.
PMID- 28496321
TI - Development of 99mTc-radiolabeled nanosilica for targeted detection of HER2
positive breast cancer.
AB - The human epidermal growth factor receptor 2 (HER2) is normally associated with a
highly aggressive and infiltrating phenotype in breast cancer lesions with
propensity to spread into metastases. In clinic, the detection of HER2 in primary
tumors and in their metastases is currently based on invasive methods. Recently,
nuclear molecular imaging techniques, including positron emission tomography and
single photon emission computed tomography (SPECT), allowed the detection of HER2
lesions in vivo. We have developed a 99mTc-radiolabeled nanosilica system,
functionalized with a trastuzumab half-chain, able to act as drug carrier and
SPECT radiotracer for the identification of HER2-positive breast cancer cells. To
this aim, nanoparticles functionalized or not with trastuzumab half-chain, were
radiolabeled using the 99mTc-tricarbonyl approach and evaluated in HER2 positive
and negative breast cancer models. Cell uptake experiments, combined with flow
cytometry and fluorescence imaging, suggested that active targeting provides
higher efficiency and selectivity in tumor detection compared to passive
diffusion, indicating that our radiolabeling strategy did not affect the
nanoconjugate binding efficiency. Ex vivo biodistribution of 99mTc-nanosilica in
a SK-BR-3 (HER2+) tumor xenograft at 4 h postinjection was higher in targeted
compared to nontargeted nanosilica, confirming the in vitro data. In addition,
viability and toxicity tests provided evidence on nanoparticle safety in cell
cultures. Our results encourage further assessment of silica 99mTc-nanoconjugates
to validate a safe and versatile nanoreporter system for both diagnosis and
treatment of aggressive breast cancer.
PMID- 28496322
TI - Photoresponsive nanocapsulation of cobra neurotoxin and enhancement of its
central analgesic effects under red light.
AB - Cobra neurotoxin (CNT), a peptide isolated from snake venom of Naja naja atra,
shows central analgesic effects in our previous research. In order to help CNT
pass through blood-brain barrier (BBB) and improve its central analgesic effects,
a new kind of CNT nanocapsules were prepared by double emulsification with
soybean lecithin and cholesterol as the shell, and pheophorbide as the
photosensitizer added to make it photoresponsive. The analgesic effects were
evaluated by hot plate test and acetic acid-induced writhing in mice. The CNT
nanocapsules had an average particle size of 229.55 nm, zeta potential of -53.00
mV, encapsulation efficiency of 84.81% and drug loading of 2.98%, when the
pheophorbide content was 1% of lecithin weight. Pheophorbide was mainly
distributed in outer layer of the CNT nanocapsules and increased the release of
the CNT nanocapsules after 650 nm illumination. The central analgesic effects
were improved after intraperitoneal injection of CNT at 25 and 50 ug.kg-1 under
650 nm irradiation for 30 min in the nasal cavity. Activation of pheophorbide by
red light generated reactive oxygen species which opened the nanocapsules and BBB
and helped the CNT enter the brain. This research provides a new drug delivery
for treatment of central pain.
PMID- 28496323
TI - A novel nanoemulsion-based method to produce ultrasmall, water-dispersible
nanoparticles from chitosan, surface modified with cell-penetrating peptide for
oral delivery of proteins and peptides.
AB - A simple and reproducible water-in-oil (W/O) nanoemulsion technique for making
ultrasmall (<15 nm), monodispersed and water-dispersible nanoparticles (NPs) from
chitosan (CS) is reported. The nano-sized (50 nm) water pools of the W/O
nanoemulsion serve as "nano-containers and nano-reactors". The entrapped polymer
chains of CS inside these "nano-reactors" are covalently cross-linked with the
chains of polyethylene glycol (PEG), leading to rigidification and formation of
NPs. These NPs possess excessive swelling properties in aqueous medium and
preserve integrity in all pH ranges due to chemical cross-linking with PEG. A
potent and newly developed cell-penetrating peptide (CPP) is further chemically
conjugated to the surface of the NPs, leading to development of a novel peptide
conjugated derivative of CS with profound tight-junction opening properties. The
CPP-conjugated NPs can easily be loaded with almost all kinds of proteins,
peptides and nucleotides for oral delivery applications. Feasibility of this
nanoparticulate system for oral delivery of a model peptide (insulin) is
investigated in Caco-2 cell line. The cell culture results for translocation of
insulin across the cell monolayer are very promising (15%-19% increase), and
animal studies are actively under progress and will be published separately.
PMID- 28496324
TI - Preparation of zein nanoparticles by using solution-enhanced dispersion with
supercritical CO2 and elucidation with computational fluid dynamics.
AB - Nanoparticles have attracted more and more attention in the medicinal field. Zein
is a biomacromolecule and can be used as a carrier for delivering active
ingredients to prepare controlled release drugs. In this article, we presented
the preparation of zein nanoparticles by solution-enhanced dispersion by
supercritical CO2 (SEDS) approach. Scanning electron microscopy and transmission
electron microscopy were applied to characterize the size and morphology of the
obtained particles. The nozzle structure and the CO2 flow rate greatly affected
the morphology and the size of the particles. The size of zein was able to be
reduced to 50-350 nm according to the different conditions. The morphologies of
the resultant zein were either sphere or the filament network consisted of
nanoparticles. The influence of the nozzle structure and the CO2 flow rate on the
velocity field was elucidated by using computational fluid dynamics. The nozzle
structure and the CO2 flow rate greatly affected the distribution of the velocity
field. However, a similar velocity field could also be obtained when the nozzle
structure or the CO2 flow rate, or both were different. Therefore, the influence
of the nozzle structure and the CO2 flow rate on the size and morphology of the
particles, can boil down to the velocity field. The results demonstrated that the
velocity field can be a potential criterion for producing nanoparticles with
controllable morphology and size, which is useful to scale-up the SEDS process.
PMID- 28496325
TI - Multifunctional and biomimetic fish collagen/bioactive glass nanofibers:
fabrication, antibacterial activity and inducing skin regeneration in vitro and
in vivo.
AB - The development of skin wound dressings with excellent properties has always been
an important challenge in the field of biomedicine. In this study, biomimetic
electrospun fish collagen/bioactive glass (Col/BG) nanofibers were prepared.
Their structure, tensile strength, antibacterial activity and biological effects
on human keratinocytes, human dermal fibroblasts and human vascular endothelial
cells were investigated. Furthermore, the Sprague Dawley rat skin defect model
was used to validate their effect on wound healing. The results showed that
compared with pure fish collagen nanofibers, the tensile strength of the Col/BG
nanofibers increased to 21.87+/-0.21 Mpa, with a certain degree of antibacterial
activity against Staphylococcus aureus. It was also found that the Col/BG
nanofibers promoted the adhesion, proliferation and migration of human
keratinocytes. Col/BG nanofibers induced the secretion of type one collagen and
vascular endothelial growth factor by human dermal fibroblasts, which further
stimulated the proliferation of human vascular endothelial cells. Animal
experimentation indicated that the Col/BG nanofibers could accelerate rat skin
wound healing. This study developed a type of multifunctional and biomimetic fish
Col/BG nanofibers, which had the ability to induce skin regeneration with
adequate tensile strength and antibacterial activity. The Col/BG nanofibers are
also easily available and inexpensive, providing the possibility for using as a
functional skin wound dressing.
PMID- 28496326
TI - Gold nanoparticles attenuate metastasis by tumor vasculature normalization and
epithelial-mesenchymal transition inhibition.
AB - Angiogenesis is a process by which vessels are formed through preexisting ones,
and this plays a key role in the progression of solid tumors. However, tumor
vessels are influenced by excessive pro-angiogenic factors, resulting in deformed
structures that facilitate the intravasation of tumor cells into the circulation
and subsequent metastasis. Moreover, abnormal tumor vessels have low blood
perfusion and thereby decreased oxygen infusion into tumors. This results in a
hostile microenvironment that promotes epithelial-mesenchymal transition (EMT), a
process in which epithelial cells lose their polarity and gain increased
motility, which is associated with metastasis and invasion. Here, we demonstrate
that gold nanoparticles (AuNPs) facilitate tumor vasculature normalization,
increase blood perfusion and alleviate hypoxia in melanoma tumors. Additionally,
AuNPs were observed to reverse EMT in tumors, accompanied by the alleviation of
lung metastasis. These AuNPs inhibited the migration of B16F10 cells and reversed
EMT in B16F10 cells, indicating that AuNPs could directly regulate EMT
independent of improvements in hypoxia. Taken together, our data demonstrated
that AuNPs could induce tumor vasculature normalization and reverse EMT,
resulting in decreased melanoma tumor metastasis.
PMID- 28496327
TI - Anorexia nervosa of the restrictive type and celiac disease in adolescence.
AB - BACKGROUND: Anorexia nervosa (AN) is usually present in adolescence with symptoms
partially overlapping celiac disease (CD), but the relationship between these two
conditions has received little attention in the literature. The aim of this work
was to explore this relationship, considering if CD could be associated with
specific baseline AN-related clinical features. METHODS: In this retrospective
study, 82 adolescent female out- and inpatients with AN of the restrictive type
(ANr), according to the Diagnostic and Statistical Manual of Mental Disorders,
Fifth Edition criteria, were recruited. CD diagnosis and related serology were
recorded, including tissue transglutaminase type-2 antibodies, endomysial
antibodies, and antibodies against deamidated forms of gliadin peptides. Eating
disorder inventory-3, Children's Depression Inventory, body mass index, age, and
disease duration data recorded at the time of blood withdrawal were also obtained
from each patient. RESULTS: Five (6.1%) subjects presented a CD disorder
associated with AN: none of the collected psychometric measures was significantly
correlated with any CD-related parameter or characterized as a specific subgroup.
CONCLUSION: CD diagnosis or serology does not relate to ANr clinical or
demographic characteristics. However, a slight increase in prevalence with
respect to the general population might be hypothesized and possibly elucidated
by further studies with an appropriate design.
PMID- 28496328
TI - Association between use of disease-modifying antirheumatic drugs and diabetes in
patients with ankylosing spondylitis, rheumatoid arthritis, or
psoriasis/psoriatic arthritis: a nationwide, population-based cohort study of
84,989 patients.
AB - PURPOSE: The aim of this study is to investigate the association between the use
of disease-modifying antirheumatic drugs (DMARDs) and diabetes mellitus (DM) in
patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA), or
psoriasis/psoriatic arthritis (PS/PSA). PATIENTS AND METHODS: This retrospective
cohort study used a nationwide, population-based administrative database to
enroll 84,989 cases with AS, RA, or PS/PSA who initiated treatment with anti
tumor necrosis factor (anti-TNF) drugs or nonbiologic DMARDs. Multivariable
analysis was used to estimate the effect of different therapies on the risk of
DM. RESULTS: The incidence rates of DM per 1,000 person-years were 8.3 for users
of anti-TNF drugs, 13.3 for users of cyclosporine (CSA), 8.4 for users of
hydroxychloroquine (HCQ), and 8.1 for users of other nonbiologic DMARDs. Compared
with the users of nonbiologic DMARDs, the multivariate-adjusted hazard ratios
(aHRs) for DM were significantly lower for those who used anti-TNF drugs with HCQ
(aHR: 0.49, 95% confidence interval [CI]: 0.36-0.66) and those who used HCQ alone
(aHR: 0.70, 95% CI: 0.63-0.78), but not for those who used anti-TNFs without HCQ
(aHR: 1.23, 95% CI: 0.94-1.60) or CSA (aHR: 1.14, 95% CI: 0.77-1.70). CONCLUSION:
The aHR for DM was lowest for patients with RA and PS/PSA who initiated treatment
with an anti-TNF agent with concomitant HCQ, followed by HCQ users. Those who
used anti-TNF agents without HCQ and other nonbiologic DMARDs had a similar risk
of DM.
PMID- 28496329
TI - Minimally invasive endoscopic resection for the treatment of sinonasal
malignancy: the outcomes and risk factors for recurrence.
AB - PURPOSE: The role of minimally invasive endoscopic resection (MIER) in the
treatment of sinonasal malignancy is controversial. Herein, we performed a
retrospective review of a large case series of sinonasal malignancy patients
treated with MIER aimed at evaluating the outcomes and identifying the risk
factors for recurrence. METHODS: Patients with sinonasal malignancy who underwent
MIER from March 2000 to May 2015 were enrolled, and their clinical data were
collected. The clinical outcomes were evaluated by determining the 5-year overall
survival (OS) and disease-free survival (DFS). The predictive factors for
survival and potential independent risk factors for recurrence were explored.
RESULTS: A total of 120 patients were enrolled, including 62 males and 58
females. The mean follow-up period was 51.4 (95% confidence interval: 44.0-59.1)
months. The most frequent histological type was mucosal malignant melanoma. The
positive margin rate was 19.2% (23/120). Seventy-one patients had the safety
anatomic plane (SAP). Age >=50 years, nodal metastasis, and not having the SAP
were found to be predictive factors for survival, and absence of SAP was found to
be an independent risk factor for recurrence. CONCLUSION: Our study indicated
that MIER is an effective and safe surgical procedure in appropriately selected
patients. Tumor resection with a safety anatomic boundary is likely to lead to
improved survival and decreased recurrence. However, a larger sample and long
term prospective observation are still required to establish the role of MIER in
treatment of sinonasal malignancy.
PMID- 28496330
TI - Differential cardiovascular profiles of sodium-glucose cotransporter 2
inhibitors: critical evaluation of empagliflozin.
AB - One of the most feared repercussions of type 2 diabetes mellitus is the risk of
adverse cardiovascular outcomes. The current antidiabetic agents on the market
have had difficulty in showing cardiovascular outcome improvement. The EMPA-REG
OUTCOME trial studied the sodium-glucose cotransporter 2 inhibitor empagliflozin
in type 2 diabetic patients at high risk of cardiovascular events. The trial
results revealed a decrease in the composite primary end points of death from
cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke in
those taking empagliflozin vs placebo. Those taking the medication also had a
significant decrease in death from any cause, death from cardiovascular cause,
and hospitalization for heart failure. The EMPA-REG trial is paradigm shifting
because it demonstrates a clear mortality benefit to cardiovascular outcomes with
a low side-effect profile, in contrast to prior outcome studies of hypoglycemic
agents. Further studies are required to better clarify the long-term safety and
efficacy of this promising class of diabetic drugs.
PMID- 28496331
TI - Clinical and genetic characteristics in a group of 45 patients with Turner
syndrome (monocentric study).
AB - INTRODUCTION: Recent years have seen a shift in perspective on Turner syndrome,
as it is no longer considered a significant disability due to therapeutic
advances. The delay of diagnosis and the underdiagnosis are common in Turner
syndrome, especially because of the great phenotypic variability and lack of firm
diagnostic criteria. AIM: Our first aim was to assess the clinical and the
cytogenetic characteristics and growth rate in growth hormone (GH)-treated
patients as compared to those with spontaneous growth. The second aim was to
analyze the Y chromosomal sequences. MATERIALS AND METHODS: We analyzed 45
patients diagnosed with Turner syndrome in Genetic Pathology Centre of Cluj
Emergency Children's Hospital. We carried out a study of the clinical features,
the correlations between the karyotype and the phenotype, and we also made a
research of Y chromosome sequences. RESULTS: The average age at diagnosis was
8.9+/-5.4 years. A significant association was observed between the number of
external phenotypical abnormalities and internal malformations (r=0.45),
particularly the cardiovascular ones (r=0.44). Patients treated with GH showed
improvement in growth rate, with final stature significantly better than in
untreated patients; benefits following treatment were greater if diagnosis was
made before the age of 5 years. Thirteen percent of patients experienced
spontaneous and complete puberty, whereas 30% experienced incomplete puberty.
Patients with the 45,X genotype had a greater stature deficit and a higher
incidence of cardiac malformations, compared with patients with 45,X/46,XX mosaic
karyotype. Y chromosome sequences were found in only one patient, who
subsequently underwent gonadectomy. CONCLUSION: The importance of this study
resides, to the best of our knowledge, in the fact that the largest group of
patients in Romania was analyzed and assessed. To draw firm conclusions on the
most valuable clinical indicators for Turner syndrome diagnosis in clinical
practice, studies on large groups of patients should be conducted.
PMID- 28496332
TI - Epithelial-to-mesenchymal transition correlates with gefitinib resistance in
NSCLC cells and the liver X receptor ligand GW3965 reverses gefitinib resistance
through inhibition of vimentin.
AB - The role of epithelial-to-mesenchymal transition in cancer drug resistance is
increasingly acknowledged. We examined whether epithelial-to-mesenchymal
transition affects gefitinib resistance in non-small cell lung cancer (NSCLC)
cells. Cell viability was detected by CCK-8 assay, VIM expression levels were
determined by quantitative real-time polymerase chain reaction. Western blot and
immunocytochemistry were performed to determine the protein expression level of
vimentin. We observed morphologic differences between gefitinib-sensitive and
insensitive cells. Compared with the sensitive parental cell line, HCC827,
vimentin expression levels were increased in HCC827 cells with acquired gefitinib
resistance. Vimentin expression was also markedly upregulated in cells with
intrinsic gefitinib resistance, and upregulated vimentin expression was
correlated with gefitinib sensitivity. Our previous study demonstrated that
coadministration of gefitinib and GW3965 resulted in decreased cell proliferation
and induced apoptosis. Therefore, we investigated the relationship among GW3965,
vimentin, and gefitinib resistance in NSCLC cells by analysis of the expression
of vimentin in cells treated with a combination of gefitinib and GW3965.
Gefitinib treatment led to increased levels of intracellular vimentin, while
combined treatment with gefitinib and GW3965 resulted in decreased vimentin
expression levels through reduction of gefitinib drug resistance in NSCLC cells.
Overall, these findings suggest that vimentin expression is associated with
sensitivity to gefitinib, and our study highlights the potential usefulness of
the drug, GW3965, for reversal of gefitinib resistance through inhibition of
vimentin expression.
PMID- 28496334
TI - Erratum: Lead identification for the K-Ras protein: virtual screening and
combinatorial fragment-based approaches [Corrigendum].
AB - [This corrects the article on p. 2575 in vol. 9, PMID: 27217775.].
PMID- 28496333
TI - Immune checkpoint blockade: the role of PD-1-PD-L axis in lymphoid malignancies.
AB - The co-inhibitory receptor programmed cell death (PD)-1, expressed by immune
effector cells, is credited with a protective role for normal tissue during
immune responses, by limiting the extent of effector activation. Its presently
known ligands, programmed death ligands (PD-Ls) 1 and 2, are expressed by a
variety of cells including cancer cells, suggesting a role for these molecules as
an immune evasion mechanism. Blocking of the PD-1-PD-L signaling axis has
recently been shown to be effective and was clinically approved in
relapsed/refractory tumors such as malignant melanoma and lung cancer, but also
classical Hodgkin's lymphoma. A plethora of trials exploring PD-1 blockade in
cancer are ongoing. Here, we review the role of PD-1 signaling in lymphoid
malignancies, and the latest results of trials investigating PD-1 or PD-L1
blocking agents in this group of diseases. Early phase studies proved very
promising, leading to the clinical approval of a PD-1 blocking agent in Hodgkin's
lymphoma, and Phase III clinical studies are either planned or ongoing in most
lymphoid malignancies.
PMID- 28496335
TI - Knockdown of a DIS3L2 promoter upstream long noncoding RNA (AC105461.1) enhances
colorectal cancer stem cell properties in vitro by down-regulating DIS3L2.
AB - A large number of studies have identified plentiful long noncoding RNAs (lncRNAs)
associated with the development of multiple cancers. Some lncRNAs have also been
found to be strongly linked with stem cell properties such as pluripotency and
differentiation. However, only in a few cases have cancer stem cell (CSC)-related
lncRNAs been studied. Commonly, the expression and function of lncRNAs are
associated with adjacent protein coding transcripts. In the present study, we
found an lncRNA (AC105461.1), a promoter upstream transcript of DIS3 mitotic
control homolog (Saccharomyces cerevisiae)-like 2 (DIS3L2), may be closely
connected with "stem cell-like" properties. We firstly investigated whether the
expression of AC105461.1 was down-regulated in colorectal cancer (CRC) tissue
samples. Subsequently, we explored the expression pattern of the lncRNA/mRNA gene
pair between AC105461.1 and DIS3L2 in 47 CRC specimens by real-time polymerase
chain reaction. The results showed that the expression of AC105461.1 was
positively correlated with that of DIS3L2. Through CRC cell lines screening
experiment, we found that AC105461.1 expression was highest in SW480 and lowest
in SW620 cells. Moreover, the results obtained by overexpression experiment
indicated that AC105461.1 expression was markedly elevated and DIS3L2 expression
level was also apparently upregulated by plasmid cDNA-AC105461.1. In contrast, we
further found that AC105461.1 expression level in AC105461.1 siRNA group was
significantly knocked down in SW480 cells. Meanwhile, DIS3L2 expression was also
markedly decreased. Importantly, we noticed that AC105461.1 overexpression
impaired CSC properties, while its knockdown enhanced CSC properties, including
self-renewal, migration, and invasion abilities. To further identify the
influence of AC105461.1 expression on CSCs properties in CRC, CD133 and CD44, as
current universal markers for characterizing CRC stem cells, were selected to
perform flow cytometry analysis. As a result, we found that AC105461.1
overexpression reduced the percentage of CD133+CD44+, whereas its knockdown
increased the percentage of CD133+CD44+. Taken together, our findings indicated
that AC105461.1 may be a regulator of DIS3L2 and a mediator of CRC stem cells,
and we speculate that AC105461.1 could be regarded as a promising biomarker and
therapeutic target for CRC.
PMID- 28496336
TI - Curcumin exerts its antitumor activity through regulation of miR-7/Skp2/p21 in
nasopharyngeal carcinoma cells.
AB - Curcumin, a natural polyphenol compound, exhibits tumor suppressive activity in a
wide spectrum of cancers, including nasopharyngeal carcinoma cells. However, the
exact molecular mechanisms governing this tumor suppressive activity remain
elusive. Multiple studies have revealed that miRNAs are critically involved in
tumorigenesis, indicating that targeting miRNAs could be a therapeutic strategy
for treating human cancer. In the current study, we set out to determine whether
curcumin regulates miR-7 expression in nasopharyngeal carcinoma cells. We found
that curcumin inhibited cell growth, induced apoptosis, retarded cell migration
and invasion, and triggered cell cycle arrest in the human nasopharyngeal
carcinoma cell lines CNE1 and CNE2. Importantly, we observed that curcumin
upregulated the expression of miR-7 and subsequently inhibited Skp2, a direct miR
7 target. Our results identified that upregulation of miR-7 by curcumin could
benefit nasopharyngeal carcinoma patients.
PMID- 28496337
TI - Immunogenicity of oncolytic vaccinia viruses JX-GFP and TG6002 in a human
melanoma in vitro model: studying immunogenic cell death, dendritic cell
maturation and interaction with cytotoxic T lymphocytes.
AB - Oncolytic virotherapy is an emerging immunotherapeutic modality for cancer
treatment. Oncolytic viruses with genetic modifications can further enhance the
oncolytic effects on tumor cells and stimulate antitumor immunity. The oncolytic
vaccinia viruses JX-594-GFP+/hGM-CSF (JX-GFP) and TG6002 are genetically modified
by secreting granulocyte-macrophage colony-stimulating factor (GM-CSF) or
transforming 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU). We compared
their properties to kill tumor cells and induce an immunogenic type of cell death
in a human melanoma cell model using SK29-MEL melanoma cells. Their influence on
human immune cells, specifically regarding the activation of dendritic cells
(DCs) and the interaction with the autologous cytotoxic T lymphocyte (CTL) clone,
was investigated. Melanoma cells were infected with either JX-GFP or TG6002 alone
or in combination with 5-FC and 5-FU. The influence of viral infection on cell
viability followed a time- and multiplicity of infection dependent manner.
Combination of virus treatment with 5-FU resulted in stronger reduction of cell
viability. TG6002 in combination with 5-FC did not significantly strengthen the
reduction of cell viability in this setting. Expression of calreticulin and high
mobility group 1 protein (HMGB1), markers of immunogenic cell death (ICD), could
be detected after viral infection. Accordingly, DC maturation was noted after
viral oncolysis. DCs presented stronger expression of activation and maturation
markers. The autologous CTL clone IVSB expressed the activation marker CD69, but
viral treatment failed to enhance cytotoxicity marker. In summary, vaccinia
viruses JX-GFP and TG6002 lyse melanoma cells and induce additional
immunostimulatory effects to promote antitumor immune response. Further
investigation in vivo is needed to consolidate the data.
PMID- 28496338
TI - The voice quality after laser surgery versus radiotherapy of T1a glottic
carcinoma: systematic review and meta-analysis.
AB - BACKGROUND AND OBJECTIVES: The voice quality assessment of laser surgery (LS) in
comparison with radiotherapy (RT) remains uncertain in T1a glottic carcinoma
treatment. This systematic review and meta-analysis were conducted to compare the
voice quality of the two treatments. METHODS: Searches were conducted in PubMed,
EMBASE, and Cochrane with the following index words: glotti*, layn*, vocal cord,
vocal, surgery, cordectomy, laser, radiation, irradiation, radiotherapy, cancer,
and carcinoma for relative studies that compared the voice quality between LS and
RT. Random-effect models were used, and heterogeneity was assessed. RESULTS: A
total of 14 studies were included in the analysis, consisting of 1 randomized
controlled trial, 1 prospective study, and 12 retrospective studies. RT has
increased the maximum phonation time (MPT; mean difference [MD] =-1.89, 95%
confidence interval [CI] =-3.66 to -0.11, P=0.04) and decreased the fundamental
frequency (MD =14.06, 95% CI =10.30-17.83, P<0.00001) in comparison with LS. No
statistical difference was observed between the two groups in terms of Voice
Handicap Index, Jitter, Shimmer, and airflow rate. CONCLUSION: RT may be a better
choice for T1a glottic carcinoma treatment compared with LS because patients
undergoing RT may have the advantage of increased MPT and decreased fundamental
frequency. However, more multicenter, randomized, controlled trials are urgently
needed to verify these differences.
PMID- 28496339
TI - FAM172A expression in circulating tumor cells for prediction of high-risk
subgroups of colorectal cancer [Retraction].
AB - [This retracts the article on p. 1933 in vol. 10, PMID: 28408845.].
PMID- 28496340
TI - Characteristics of circulating tumor cells in organ metastases, prognosis, and T
lymphocyte mediated immune response.
AB - Circulating tumor cells (CTCs) possess profound influence on tumor metastases and
disease progression. This study aimed to investigate the correlation of CTCs with
clinical characteristics and T-cell immunity, and to explore whether CTCs and the
subpopulations can serve as an independent prognostic factor in advanced non
small cell lung cancer (NSCLC). A prospective study was conducted in late stages
of NSCLC patients. The levels of overall CTCs and the three subpopulation CTCs
were enumerated using the CanPatrolTM CTC enrichment system. The information
about the patients which included the clinical characteristics, survival status
at the 200th day postdiagnosis, and the levels of T cells was collected. Mann
Whitney U test, Kruskal-Wallis H test, Cox regression, and Spearman's rank
correlation coefficient were the statistical methods used in this study. We
detected CTCs in 27 of the 31 eligible patients; the level of epithelial
mesenchymal circulating tumor cells (EMCTCs) was higher than that of epithelial
circulating tumor cells and that of mesenchymal circulating tumor cells (MCTCs)
in the majority of NSCLC patients. Organ metastases were positively associated
with the levels of overall CTCs, EMCTCs, and MCTCs (P<0.05). EMCTCs and MCTCs
were associated with worse clinical outcomes. Additionally, the levels of EMCTCs
were negatively associated with the levels of CD3+ T cells (P=0.01) and CD8+ T
cells (P=0.04). In conclusion, the levels of CTCs were positively associated with
organ metastases, particularly bone metastases, but were negatively associated
with T-cell levels. The levels of EMCTCs and MCTCs had negative prognostic value.
PMID- 28496341
TI - The coexpression of EphB4 and EphrinB2 is associated with poor prognosis in HER2
positive breast cancer [Retraction].
AB - [This retracts the article on p. 1735 in vol. 10, PMID: 28356761.].
PMID- 28496342
TI - Sialylation facilitates self-assembly of 3D multicellular prostaspheres by using
cyclo-RGDfK(TPP) peptide.
AB - BACKGROUND: Prostaspheres-based three dimensional (3D) culture models have
provided insight into prostate cancer (PCa) biology, highlighting the importance
of cell-cell interactions and the extracellular matrix (EMC) in the tumor
microenvironment. Although these 3D classical spheroid platforms provide a
significant advance over 2D models mimicking in vivo tumors, the limitations
involve no control of assembly and structure with only limited spatial or
glandular organization. Here, matrix-free prostaspheres from human metastatic
prostate carcinoma PC3 and DU145 cell lines and their respective gemcitabine
resistant (GemR) variants were generated by using cyclic Arg-Gly-Asp-D-Phe-Lys
peptide modified with 4-carboxybutyl-triphenylphosphonium bromide (cyclo
RGDfK(TPP)). MATERIALS AND METHODS: Microscopic imaging, immunocytochemistry
(ICC), flow cytometry, sialidase, and WST-1 cell viability assays were used to
evaluate the formation of multicellular tumor spheroid (MCTS), cell survival,
morphologic changes, and expression levels of alpha2,6 and alpha2,3 sialic acid
(SA) and E- and N-cadherin in DU145, PC3, and their GemR variants. RESULTS: By
using the cyclo-RGDfK(TPP) peptide platform in a dose- and time-dependent manner,
both DU145 and DU145GemR cells formed small MCTS. In contrast, PC3 and PC3GemR
cells formed irregular multicellular aggregates at all concentrations of cyclo
RGDfK(TPP) peptide, even after 6 days of incubation. ICC and flow cytometry
results revealed that DU145 cells expressed higher amounts of E-cadherin but
lower N-cadherin compared with PC3 cells. By using Maackia amurensis (alpha2,3-SA
specific MAL-II) and Sambucus nigra (alpha2,6-SA specific SNA) lectin-based
cytochemistry staining and flow cytometry, it was found that DU145 and DU145GemR
cells expressed 5 times more alpha2,6-SA than alpha2,3-SA on the cell surface.
PC3 cells expressed 4 times more alpha2,3-SA than alpha2,6-SA, and the PC3GemR
cells showed 1.4 times higher alpha2,6-SA than alpha2,3-SA. MCTS volume was dose
dependently reduced following pretreatment with alpha2,6-SA-specific
neuraminidase (Vibrio cholerae). Oseltamivir phosphate enhanced cell aggregation
and compaction of 3D MCTS formed with PC3 cells. CONCLUSION: The relative levels
of specific sialoglycan structures on the cell surface correlate with the ability
of PCa cells to form avascular multicellular prostaspheres.
PMID- 28496343
TI - Gastroenterologist and nurse management of symptoms after pelvic radiotherapy for
cancer: an economic evaluation of a clinical randomized controlled trial (the
ORBIT study).
AB - BACKGROUND: Over 20 distressing gastrointestinal symptoms affect many patients
after pelvic radiotherapy, but in the United Kingdom few are referred for
assessment. Algorithmic-based treatment delivered by either a consultant
gastroenterologist or a clinical nurse specialist has been shown in a randomized
trial to be statistically and clinically more effective than provision of a self
help booklet. In this study, we assessed cost-effectiveness. METHODS: Outcomes
were measured at baseline (pre-randomization) and 6 months. Change in quality
adjusted life years (QALYs) was the primary outcome for the economic evaluation;
a secondary analysis used change in the bowel subset score of the modified
Inflammatory Bowel Disease Questionnaire (IBDQ-B). Intervention costs, British
pounds 2013, covered visits with the gastroenterologist or nurse, investigations,
medications and treatments. Incremental outcomes and incremental costs were
estimated simultaneously using multivariate linear regression. Uncertainty was
handled non-parametrically using bootstrap with replacement. RESULTS: The mean
(SD) cost of treatment was L895 (499) for the nurse and L1101 (567) for the
consultant. The nurse was dominated by usual care, which was cheaper and achieved
better outcomes. The mean cost per QALY gained from the consultant, compared to
usual care, was L250,455; comparing the consultant to the nurse, it was L25,875.
Algorithmic care produced better outcomes compared to the booklet only, as
reflected in the IBDQ-B results, at a cost of ~L1,000. CONCLUSION: Algorithmic
treatment of radiation bowel injury by a consultant or a nurse results in
significant symptom relief for patients but was not found to be cost-effective
according to the National Institute for Health and Care Excellence (NICE)
criteria.
PMID- 28496344
TI - Adherence to disease-modifying therapies and its impact on relapse, health
resource utilization, and costs among patients with multiple sclerosis.
AB - PURPOSE: To evaluate adherence to disease-modifying therapies (DMTs) among
patients with multiple sclerosis (MS) initiating oral and injectable DMTs, and to
estimate the impact of adherence on relapse, health resource utilization, and
medical costs. PATIENTS AND METHODS: Commercially insured MS patients (aged 18-65
years, two or more MS diagnoses, one or more DMT claims) with continuous
eligibility 12 months before and after the first DMT claim date (index date) and
no DMT claim during the pre-index period were identified from a large commerical
claims database for the period from January 1, 2008, to September 30, 2015.
Adherence to the index DMT was measured by the 12-month post-index proportion of
days covered (PDC) and compared between oral and injectable DMT initiators. After
adjustment for sex, age at index DMT, and comorbidities, regression models
examined the relationship between adherence and relapse risk, MS-related health
resource utilization, and non-drug medical costs (2015 US$). RESULTS: The study
covered 12,431 patients and nine DMTs. Adherence to the index DMT did not differ
significantly between oral (n=1,018) and injectable (n=11,413) DMTs when assessed
by mean PDC (0.7257+/-0.2934 vs 0.7259+/-0.2869, respectively; P=0.0787), or
percentages achieving PDC >=0.8 (61.4% vs 58.6%, respectively; P=0.0806).
Compared to non-adherence, adherence to DMT significantly reduced the likelihood
of relapse in the post-index 12 months by 42%, hospitalization by 52%, and
emergency visits by 38% (all, P<0.0001). Adherent patients would be expected to
have on average 0.7 fewer outpatient visits annually versus non-adherent patients
(P<0.0001). Based on the differences in predicted mean costs, adherence (vs non
adherence) would decrease the total annual medical care costs by $5,816 per
patient, including hospitalization costs by $1,953, emergency visits by $171, and
outpatient visits by $2,802. CONCLUSION: Adherence remains suboptimal but
comparable between oral and injectable DMTs. Potential health and economic
benefits underscore the importance of improving adherence in MS.
PMID- 28496345
TI - Glucose-lowering therapies, adequacy of metabolic control, and their relationship
with comorbid depression in outpatients with type 2 diabetes in a tertiary
hospital in Kenya.
AB - BACKGROUND: Depression and diabetes mellitus are important comorbid conditions
with serious health consequences. When depression and diabetes are comorbid,
depression negatively affects self-management activities of diabetes with serious
consequences. Relationship between treatment regimens of diabetes, the adequacy
of glycemic control, and occurrence of comorbid depression is not known among our
patients. PATIENTS AND METHODS: This was a cross-sectional descriptive study at
the outpatient diabetes clinic of the Kenyatta National Hospital where 220
ambulatory patients with type 2 diabetes on follow-up were systematically
sampled. Sociodemographic data and clinical information were documented. The
Patient Health Questionnaire-9 (PHQ-9) was used to assess depression.
Ethylenediaminetetraacetic acid-anticoagulated blood was used for glycated
hemoglobin (HbA1C) assay on automated system, COBAS INTEGRA machine. RESULTS: Two
hundred twenty patients with type 2 diabetes were enrolled. The prevalence of
comorbid depression by PHQ-9 was 32.3% (95% confidence interval: 26.4%-38.6%).
The majority, 69.5%, had poor glycemic control, HbA1C >7.0%, mean HbA1C was
8.9%+/-2.4%. Half, 50.4%, of the study subjects were on insulin-containing
regimens. Over 8% (84.5%) of the participants with comorbid depression had poor
glycemic control, which worsened with increasing severity of depression. There
was significant correlation between comorbid depression and poor glycemic
control, which is more consistent in the insulin-treated patients. However,
patients on oral agents only, both with and without comorbid depression, were
similar in their glycemic control. CONCLUSION: Among our type 2 diabetic
population with comorbid depression, a large proportion had poor glycemic
control, which worsened with increasing severity of depression. The insulin
treatment increased the odds of comorbid depression and poor glycemic control in
patients. It is justifiable to screen for comorbid depression in patients with
type 2 diabetes who are in poor glycemic control, especially the insulin-treated,
and then provide specific and appropriate interventions that are necessary to
optimize their metabolic outcomes.
PMID- 28496346
TI - Do we need to measure vitamin B12 and magnesium in morbidly obese patients with
type 2 diabetes mellitus?
AB - OBJECTIVE: We aimed to investigate the prevalence of B12 deficiency in metformin
treated, morbidly obese, type 2 diabetes mellitus (T2DM) patients, compared to
morbidly obese controls, as well as to evaluate the magnesium status. DESIGN:
Retrospective cross-sectional analysis of plasma vitamin B12, plasma magnesium,
glucometabolic status and clinical measurements in all consecutive morbidly obese
patients was conducted during 1 year. SETTING: Outpatient Clinic of Obesity Care.
SUBJECTS: One hundred forty-seven patients were evaluated: 107 morbidly obese
controls and 40 metformin-treated, morbidly obese patients with T2DM. MAIN
OUTCOME MEASURES: Circulating plasma concentrations of vitamin B12 (cobalamin),
magnesium, clinical measurements and metformin medication. RESULTS: There were
differences between the two groups regarding age, sagittal diameter, glucose
parameters and magnesium concentrations. Longer diabetes duration was associated
with lower magnesium. Metformin-treated T2DM patients had lower magnesium (0.76+/
0.07 mmol/L) than controls (0.82+/-0.07 mmol/L). A subgroup analysis of 26 non
metformin-treated T2DM patients showed a normal magnesium concentration compared
to controls, that is, 0.81+/-0.06 mmol/L. We found no statistical difference in
B12 concentrations between the two groups. CONCLUSION: To fully benefit from
metformin medication, routine testing of B12 as well as magnesium in metformin
treated, morbidly obese patients should be performed, with consideration of
substitution to avoid low levels.
PMID- 28496347
TI - Hearing thresholds in adult Nigerians with diabetes mellitus: a case-control
study.
AB - OBJECTIVES: To determine the prevalence, types and severity of hearing loss and
associated factors in a hospital population of adult Nigerians with diabetes
mellitus. SUBJECTS AND METHODS: This study was a prospective hospital-based study
conducted at the Otorhinolaryngology and Diabetic Clinics of the University of
Nigeria Teaching Hospital (UNTH) Ituku-Ozalla, Enugu, for a period of 12 months.
Consecutively presenting eligible adult diabetics and their age- and sex-matched
healthy controls were recruited. Each case and control participant had clinical
and otologic examination, followed by pure tone audiometry. Data were analyzed
using descriptive and comparative statistics. RESULTS: There were 224 patients
and 192 control participants. The patients comprised 112 males and 112 females
(sex ratio=1:1), whose mean age was 47.6 years (range: 26-80 years). The
prevalence of hearing loss was 46.9%. This comprised 43.8% sensorineural and 3.1%
conductive hearing losses. The distribution of hearing loss by severity was mild
25.0%, moderate 15.6% and severe 6.3%. The controls comprised 96 males and 96
females whose mean age was 44.6 years (range: 25-79 years). The prevalence of
hearing loss was significantly higher overall and by type (sensorineural hearing
loss, conductive hearing loss) in cases compared with controls. CONCLUSION: The
prevalence of hearing loss among diabetic adults at UNTH, Enugu, is comparatively
high. Hearing loss is predominantly sensorineural and often mild to moderate in
severity. Routine audiometric evaluation of all adult diabetics at UNTH is
recommended.
PMID- 28496348
TI - Role of sodium glucose cotransporter-2 inhibitors in type I diabetes mellitus.
AB - The burden of diabetes mellitus (DM) in general has been extensively increasing
over the past few years. Selective sodium glucose cotransporter-2 (SGLT2)
inhibitors were extensively studied in type 2 DM and found to have sustained
urinary glucose loss, improvement of glycemic control, in addition to their
proven metabolic effects on weight, blood pressure, and cardiovascular benefits.
Type 1 DM (T1D) patients clearly depend on insulin therapy, which till today
fails to achieve the optimal glycemic control and metabolic targets that are
needed to prevent risk of complications. New therapies are obviously needed as an
adjunct to insulin therapy in order to try to achieve optimal control in T1D.
Many oral diabetic medications have been tried in T1D patients as an adjunct to
insulin treatment and have shown conflicting results. Adjunctive use of SGLT2
inhibitors in addition to insulin therapies in T1D was found to have the
potential to improve glycemic control along with decrease in the insulin doses,
as has been shown in certain animal and short-term human studies. Furthermore,
larger well-randomized studies are needed to better evaluate their efficacy and
safety in patients with T1D. Euglycemic diabetic ketoacidosis incidences were
found to be increased among users of SGLT2 inhibitors, although the incidence
remains very low. Recent beneficial effects of ketone body production and this
shift in fuel energetics have been suggested based on the findings of protective
cardiovascular benefits associated with one of the SGLT2 inhibitors.
PMID- 28496349
TI - Effect of vitamin K supplementation on insulin sensitivity: a meta-analysis.
AB - OBJECTIVE: To perform a systematic review and meta-analysis of randomized,
placebo-controlled trials to assess the effect of vitamin K supplementation on
insulin sensitivity. DATA SOURCES: MEDLINE, the Cochrane Library, CINAHL, Web of
Science, Scopus, clinicaltrials.gov, and clinicaltrialresults.org were searched
up to January 2017. Reference lists of related papers were also scanned. STUDY
SELECTION: Randomized controlled trials were selected if they compared vitamin K
supplementation with placebo or no treatment and reported homeostasis model
assessment of insulin resistance, fasting plasma glucose, fasting plasma insulin,
C-reactive protein, adiponectin, leptin, or interleukin-6 levels. DATA
EXTRACTION: Data extraction and study quality assessment were performed
independently by two investigators using a standardized data extraction form. Any
inconsistencies were resolved by a third reviewer. Effect estimates were pooled
using inverse-variance weighted method. Heterogeneity was assessed by the I2 and
Q statistic. RESULTS: A total of eight trials involving 1,077 participants met
the inclusion criteria. A wide variety of participants were enrolled, including
older men, postmenopausal women, prediabetic premenopausal women, and
participants with a history of diabetes, hypertension, or vascular disease.
Vitamin K1 and vitamin K2 (MK-4 and MK-7 subtypes) were assessed. Supplementation
period ranged from 4 weeks to 3 years. Vitamin K supplementation did not affect
insulin sensitivity as measured by homeostasis model assessment of insulin
resistance, fasting plasma glucose, fasting plasma insulin, C-reactive protein,
adiponectin, leptin, and interleukin-6 levels. CONCLUSION: Our analysis suggests
no effect of vitamin K supplementation on insulin sensitivity.
PMID- 28496350
TI - Intravenous citrulline generation test to assess intestinal function in intensive
care unit patients.
AB - BACKGROUND: Assessment of a quantifiable small intestinal function test is
cumbersome. Fasting citrulline concentrations have been proposed as a measure of
enterocyte function and elaborated into a citrulline generation test (CGT), which
is applicable only when glutamine is administered orally. CGT is an oral test,
limiting its use, for example, in critically ill patients. OBJECTIVE: Assessment
of normative values and feasibility of an intravenously performed CGT in
intensive care unit (ICU) patients with presumed gastrointestinal motility
disturbances, especially when performed intravenously. DESIGN: CGT reference
values were determined in 16 stable ICU patients using two different CGT methods,
namely following either enteral or intravenous glutamine administration and both
with simultaneous arterial and venous plasma citrulline sampling at six time
points. Plasma amino acid analysis was performed using reverse-phase high
performance liquid chromatography. RESULTS: The median total generation of
citrulline in 90 min (CGT iAUCT90) was markedly higher with arterial citrulline
sampling compared with venous citrulline sampling, being 724+/-585 and 556+/-418
umol/L/min for enteral glutamine, respectively (p=0.02) and 977+/-283 and 769+/
231 umol/L/min for intravenous glutamine, respectively (p=0.0004). The median
slope (time-dependent increase) for plasma arterial and venous citrulline during
the CGT was 0.20+/-0.16 and 0.18+/-0.12 umol/L/min for enteral glutamine,
respectively (p=0.004) and 0.22+/-0.16 and 0.19+/-0.05 umol/L/min for intravenous
glutamine, respectively (p=0.02). CONCLUSION: Intravenous glutamine
administration combined with arterial plasma citrulline sampling yielded the
least variation in CGT characteristics in stable ICU patients. A 2-point
measurement test had comparable test characteristics as a 6-point measurement CGT
and seems promising.
PMID- 28496351
TI - Fatigue in patients with inflammatory bowel disease is associated with distinct
differences in immune parameters.
AB - BACKGROUND: Although it is well recognized that fatigue is an important problem
in many of the quiescent inflammatory bowel disease (IBD) patients, it is unknown
whether the immune status is different in fatigued versus non-fatigued patients.
In this study, we contrasted various characteristics of the immune system in
fatigued against non-fatigued patients with IBD in clinical remission. PATIENTS
AND METHODS: Patients with IBD in clinical remission were phenotyped according to
the Montreal classification, and the checklist individual strength-fatigue (CIS
fatigue) was used to assess fatigue (CIS-fatigue >= 35). Flow cytometry on
peripheral blood samples was used to investigate differences in leukocyte
subsets. The expression of various cytokines was determined in stimulated whole
blood and serum samples using enzyme-linked immunosorbent assay. Differences
between fatigued and non-fatigued patients with IBD were assessed. RESULTS: In
total, 55 patients were included in the fatigue group (FG) and 29 patients in the
non-fatigue group (NFG). No differences in demographic and clinical
characteristics were observed between the groups. Flow cytometry data showed a
significantly lower percentage of monocytes (p = 0.011) and a higher percentage
of memory T-cells (p = 0.005) and neutrophils (p = 0.033) in the FG compared with
the NFG. Whole blood stimulation showed increased TNF-alpha (p = 0.022) and IFN
gamma (p = 0.047) in the FG. The median serum level was significantly higher for
IL-12 (p < 0.001) and IL-10 (p = 0.005) and lower for IL-6 (p = 0.002) in the FG
compared with NFG. CONCLUSION: Significant differences in immune profile between
fatigued and non-fatigued patients with IBD in clinical remission were found,
which point out to a chronically active and Th1-skewed immune system in patients
with fatigue. Whether these immune differences are directly involved in the
fatigue complaints via immune-to-brain communication pathways remains to be
determined. As such, further exploration of the underlying immune effects
associated with fatigue is warranted to determine potential treatment options.
PMID- 28496352
TI - Identification of expanded T-cell clones by spectratyping in nonfunctioning
kidney transplants.
AB - BACKGROUND: The aim of this study was the application of complementarity
determining region-3 spectratyping analysis to determine T-cell-repertoire
complexity and to detect T-cell-clone expansion, as a measure of immune response
in nonfunctioning kidney transplants (group hemodialysis-transplant [HD-Tx]),
nontransplanted dialysis patients (group hemodialysis [HD]), and normal subjects
as controls (group C). PATIENTS AND METHODS: Analysis of T-cell receptor (TCR)
diversity by spectratyping was applied to peripheral blood samples collected from
21 subjects: eight in group HD-Tx, seven in group HD, and six in group C.
RESULTS: Considering the extent of the skew in TCR variable region repertoires as
a measure of clonal T cells, we found that the number of altered spectra showed a
progressive increase from normal subjects to dialysis patients and to
nonfunctioning kidney transplants, respectively. Healthy subjects had the lowest
number of altered spectra, and patients with nonfunctioning kidney transplants
the highest. Differences were significant for group HD-Tx vs group C (P=0.017)
and group HD vs group C (P=0.015), but not between nonfunctioning kidney
transplant recipients and dialysis patients (group HD-Tx vs group HD).
CONCLUSION: Although dialysis appears to be a weaker trigger for clonal expansion
of T cells, our data suggest that the utilization of complementarity-determining
region-3 spectratyping analysis of the TCR repertoire might be useful to monitor
specific immunoactivation in patients before and after kidney transplantation.
PMID- 28496353
TI - Early manifestations of renal disease in patients with tuberous sclerosis
complex.
AB - OBJECTIVES: Renal manifestations are the second most significant cause of
morbidity and mortality in patients with tuberous sclerosis complex (TSC), and
include renal cysts, angiomyolipomas, fat-poor lesions, and malignant tumors.
These lesions begin in childhood and often lead to chronic kidney disease (CKD).
Little is known on the incidence of early modifiable risk factors of CKD, such as
proteinuria and hypertension, or subtle decreases in glomerular filtration rate
that correspond to the early stages of CKD in children with TSC. The impact of
genotype on these early manifestations of CKD has not been investigated. DESIGN:
Retrospective chart review of 84 children and young adults with TSC.
MEASUREMENTS: This study assessed the prevalence of hypertension, renal
impairment, and proteinuria, as well as the genotype-phenotype correlations.
RESULTS: Children and young adults with TSC2 mutations had a significantly higher
rate of renal lesions, hypertension (36% vs 14%), and decreased renal function
than those with TSC1 mutations. CONCLUSION: On the basis of estimated glomerular
filtration rate and blood pressure, our findings are consistent with the
hypothesis that TSC2 mutations are associated with more severe early renal
involvement in children. There is a compelling need for close collaboration of
nephrologists and neurologists to provide care to pediatric patients with TSC to
improve screening and management of early manifestations of renal disease.
PMID- 28496354
TI - Factors associated with prescription opioid misuse in a cross-sectional cohort of
patients with chronic non-cancer pain.
AB - OBJECTIVE: To examine demographic features, psychosocial characteristics, pain
specific behavioral factors, substance abuse history, sleep, and indicators of
overall physical function as predictors of opioid misuse in patients presenting
for new patient evaluation at a tertiary pain clinic. METHODS: Overall, 625
patients with chronic non-cancer pain prospectively completed the Collaborative
Health Outcomes Information Registry, assessing pain catastrophizing, National
Institutes of Health Patient-Reported Outcomes Measurement Information System
standardized measures (pain intensity, pain behavior, pain interference, physical
function, sleep disturbance, sleep-related impairment, anger, depression,
anxiety, and fatigue), and substance use history. Additional information
regarding current opioid prescriptions and opioid misuse was examined through
retrospective chart review. RESULTS: In all, 41 (6.6%) patients presented with
some indication of prescription opioid misuse. In the final multivariable
logistic regression model, those with a history of illicit drug use (odds ratio
[OR] 5.45, 95% confidence interval [CI] 2.48-11.98, p<0.0001) and a current
opioid prescription (OR 4.06, 95% CI 1.62-10.18, p=0.003) were at elevated risk
for opioid misuse. Conversely, every 1-h increase in average hours of nightly
sleep decreased the risk of opioid misuse by 20% (OR 0.80, 95% CI 0.66-0.97,
p=0.02). CONCLUSION: These findings indicate the importance of considering
substance use history, current opioid prescriptions, and sleep in universal
screening of patients with chronic non-cancer pain for opioid misuse. Future work
should target longitudinal studies to verify the causal relationships between
these variables and subsequent opioid misuse.
PMID- 28496355
TI - Cannabis as a substitute for prescription drugs - a cross-sectional study.
AB - BACKGROUND: The use of medical cannabis is increasing, most commonly for pain,
anxiety and depression. Emerging data suggest that use and abuse of prescription
drugs may be decreasing in states where medical cannabis is legal. The aim of
this study was to survey cannabis users to determine whether they had
intentionally substituted cannabis for prescription drugs. METHODS: A total of
2,774 individuals were a self-selected convenience sample who reported having
used cannabis at least once in the previous 90 days. Subjects were surveyed via
an online anonymous questionnaire on cannabis substitution effects. Participants
were recruited through social media and cannabis dispensaries in Washington
State. RESULTS: A total of 1,248 (46%) respondents reported using cannabis as a
substitute for prescription drugs. The most common classes of drugs substituted
were narcotics/opioids (35.8%), anxiolytics/benzodiazepines (13.6%) and
antidepressants (12.7%). A total of 2,473 substitutions were reported or
approximately two drug substitutions per affirmative respondent. The odds of
reporting substituting were 4.59 (95% confidence interval [CI], 3.87-5.43)
greater among medical cannabis users compared with non-medical users and 1.66
(95% CI, 1.27-2.16) greater among those reporting use for managing the
comorbidities of pain, anxiety and depression. A slightly higher percentage of
those who reported substituting resided in states where medical cannabis was
legal at the time of the survey (47% vs. 45%, p=0.58), but this difference was
not statistically significant. DISCUSSION: These patient-reported outcomes
support prior research that individuals are using cannabis as a substitute for
prescription drugs, particularly, narcotics/opioids, and independent of whether
they identify themselves as medical or non-medical users. This is especially true
if they suffer from pain, anxiety and depression. Additionally, this study
suggests that state laws allowing access to, and use of, medical cannabis may not
be influencing individual decision-making in this area.
PMID- 28496357
TI - Incidence and risk factors of persistent low back pain following posterior
decompression and instrumented fusion for lumbar disk herniation.
AB - INTRODUCTION: The aim of this study was to explore the incidence and risk factors
of persistent low back pain (PLBP) following posterior decompression and
instrumented fusion for lumbar disk herniation and to provide references in
decision-making and surgical planning for both spinal surgeons and surgically
treated patients. PATIENTS AND METHODS: By retrieving the medical records from
January 2013 to December 2016, 221 patients were retrospectively reviewed.
Patients were classified as having PLBP if numeric rating scale (NRS) scores were
>50 at all postoperative follow-up time points (3 months, 6 months, and 12
months). According to the occurrence of PLBP, patients were divided into two
groups: PLBP group and non (N)-PLBP group. To investigate risk values for PLBP,
the following three categorized factors were analyzed statistically. Patient
characteristics: age, gender, body mass index (BMI), preoperative low back pain,
comorbidity, smoking, and drinking. Surgical variables: surgical strategy,
surgical segment, the number of fusion levels, surgery time, blood loss, and size
of incision. Radiographic parameters: preoperative lumbar lordosis (LL),
correction of LL at immediate postoperation, Modic changes, and preoperative
paraspinal muscle degeneration. RESULTS: PLBP was detected in 16 patients and
were enrolled into the PLBP group. There was no difference between the two groups
in age, gender, BMI, comorbidity, smoking, and drinking. The preoperative low
back pain was more severe in the PLBP group than that in the N-PLBP group. There
was no difference in surgery time, blood loss, surgical strategy, number of
fusion levels, and the size of incision. Surgery segment at L5-S1 was more
prevalent in the PLBP group than that in the N-PLBP group, and there was no
difference in preoperative LL, correction of LL, preoperative lumbar mobility,
and Modic changes. The fatty infiltration rate (FIR) was larger in the PLBP group
than that in the N-PLBP group. Multivariate logistic regression model revealed
that preoperative low back pain (NRS > 35), surgery segment at L5-S1, and FIR >
15% were independently associated with PLBP. CONCLUSION: The incidence of PLBP
following posterior decompression and instrumented fusion for lumbar disk
herniation is 7.2%, and the risk factors include preoperative low back pain,
surgery segment at L5-S1, and preoperative paraspinal muscle degeneration.
PMID- 28496356
TI - Evaluation of a specialized yoga program for persons with a spinal cord injury: a
pilot randomized controlled trial.
AB - OBJECTIVES: The purpose of this randomized controlled trial was to evaluate the
effects of a specialized yoga program for individuals with a spinal cord injury
(SCI) on pain, psychological, and mindfulness variables. MATERIALS AND METHODS:
Participants with SCI (n=23) were outpatients or community members affiliated
with a rehabilitation hospital. Participants were randomized to an Iyengar yoga
(IY; n=11) group or to a 6-week wait-list control (WLC; n=12) group. The IY group
participated in a twice-weekly 6-week seated IY program; the WLC group
participated in the same yoga program, after the IY group's yoga program had
ended. Pain, psychological, and mindfulness measures were collected at two time
points for both groups (within 1-2 weeks before and after program 1 and at a
third time point for the WLC group (within 1 week after program 2). RESULTS:
Linear mixed-effect growth models were conducted to evaluate the main effects of
group at T2 (postintervention), controlling for T1 (preintervention) scores. T2
depression scores were lower (F1,18=6.1, P<0.05) and T2 self-compassion scores
higher (F1,18=6.57, P< 0.05) in the IY group compared to the WLC group. To
increase sample size and power, the two groups were combined and analyzed across
time by comparing pre- and postintervention scores. Main effects of time were
found for depression scores, (F1,14.83=6.62, P<0.05), self-compassion,
(F1,16.6=4.49, P<0.05), mindfulness (F1,16.79=5.42, P<0.05), mindful observing
(F1,19.82=5.06, P<0.05), and mindful nonreactivity, (F1,16.53=4.92, P<0.05), all
showing improvement after the intervention. DISCUSSION: The results indicated
that a specialized 6-week yoga intervention reduced depressive symptoms and
increased self-compassion in individuals with SCI, and may also have fostered
greater mindfulness.
PMID- 28496358
TI - Analgesic efficacy, adverse effects, and safety of oxycodone administered as
continuous intravenous infusion in patients after total hip arthroplasty.
AB - BACKGROUND: Total hip arthroplasty (THA) causes extensive tissue damage and
severe pain. This study aimed to assess the analgesic efficacy, adverse effects
(AEs), and safety of continuous intravenous (iv) oxycodone infusion with
ketoprofen (injected into the iv line) in patients after THA, and to assay serum
oxycodone levels. PATIENTS AND METHODS: Fourteen patients, aged 59-82 years with
American Society of Anesthesiologists (ASA) classification I or III, underwent
THA with intrathecal analgesia and sedation induced by iv propofol. After the
surgery, oxycodone (continuous iv infusion) at a dose of 1 mg/h (five patients)
or 2 mg/h (nine patients) with 100 mg ketoprofen (injected into the iv line) was
administered to each patient every 12 h. Pain was assessed using a numerical
rating scale (NRS: 0 - no pain, 10 - the most severe pain) at rest and during
movement. AEs, including hemodynamic unsteadiness, nausea, vomiting, pruritus,
cognitive impairment, and respiratory depression, were registered during the
first 24 h after surgery. RESULTS: Oxycodone (continuous iv infusion) at a dose
of 2 mg/h with ketoprofen (100 mg) administered every 12 h provided satisfactory
analgesia in all nine patients without the need of rescue analgesics within the
first 24 h after THA. In three out of five patients, oxycodone at 1 mg/h was
effective. Oxycodone did not induce drowsiness, vomiting, pruritus, respiratory
depression, or changes in blood pressure. Bradycardia appeared in two patients,
and nausea was observed in one patient. CONCLUSION: Oxycodone infusion with
ketoprofen administered by iv is effective in patients after THA. Intravenous
infusion of oxycodone is a predictable, stable, and safe method of drug
administration.
PMID- 28496359
TI - Efficacy of CR4056, a first-in-class imidazoline-2 analgesic drug, in comparison
with naproxen in two rat models of osteoarthritis.
AB - PURPOSE: CR4056, (2-phenyl-6-(1H-imidazol-1yl) quinazoline), an imidazoline-2
(I2) receptor ligand, is a promising analgesic drug that has been reported to be
effective in several animal models of pain. The aim of this study was to evaluate
the effects of CR4056 in two well-established rat models of osteoarthritis (OA),
mimicking the painful and structural components of human OA. METHODS: Knee OA was
induced either by single intra-articular injection of monoiodoacetate (MIA) or by
medial meniscal tear (MMT) in the right knee of male rats. In the MIA model,
allodynia and hyperalgesia were measured as paw withdrawal threshold to
mechanical stimulation. In the MMT model, pain behavior was analyzed as weight
bearing asymmetry (i.e. difference in hind paw weight distribution, HPWD) between
the injured and the contralateral limbs. RESULTS: Acute oral administration of
CR4056, 14 days after MIA injection, significantly and dose-dependently reduced
allodynia and hyperalgesia 90 minutes after treatment, whereas acute naproxen
administration significantly reduced allodynia but not hyperalgesia. After 7 days
of repeated treatment, both CR4056 and naproxen showed significant anti-allodynic
and anti-hyperalgesic effects in the MIA model. Rats undergoing MMT surgery
developed a significant and progressive asymmetry in HPWD compared with sham
operated animals. Repeated treatment with CR4056 significantly reduced the
progression of the pain behavior, whereas naproxen had no effects. CONCLUSION:
The data presented here show that the I2 ligand CR4056 could be a new effective
treatment for OA pain. The compound is currently under Phase II clinical
evaluation for this indication.
PMID- 28496360
TI - Epidural anesthesia for labor and delivery in a patient with May-Hegglin anomaly:
a case report.
AB - We report a case of May-Hegglin anomaly (MHA) in a woman who had a successful
labor and delivery under epidural anesthesia. MHA is an inherited
thrombocytopenia easily misdiagnosed as idiopathic (immune) thrombocytopenic
purpura (ITP). Early and appropriate diagnosis of MHA during pregnancy is
essential for optimal maternal and neonatal delivery outcome. Additionally, it
can avoid unnecessary diagnostic studies, such as bone marrow aspiration and
biopsy, and even harmful therapies with corticosteroids, immunosuppressive
agents, and splenectomy. Consequently, the most serious impacts of this disease
are iatrogenic managements due to misdiagnosis. It seems that in patients with
MHA, adequate clinical coagulation is far more dependent on adequate platelet
function than any particular platelet count. The diagnosis of MHA may pose a
challenge for clinicians managing pregnant women with thrombocytopenia.
PMID- 28496362
TI - Metaplastic breast carcinoma with upper limb gangrene.
AB - Metaplastic breast carcinomas (MBCs) are rapidly growing tumors with histological
heterogeneity, and triple negative receptor status. The aim of this case report
is to highlight a case of advanced MBC with axillary artery infiltration leading
to gangrene of the ipsilateral upper limb, in a young woman.
PMID- 28496361
TI - Improved immediate breast reconstruction as a result of oncoplastic
multidisciplinary meeting.
AB - INTRODUCTION: The National Institute for Health and Clinical Excellence
guidelines recommend that breast reconstruction should be available to all women
undergoing mastectomy and discussed at the initial surgical consultation (2002,
and updated 2009). The National Mastectomy and Breast Reconstruction Audit (2009)
showed that 21% of mastectomy patients underwent immediate breast reconstruction
(IBR) and 11% had delayed breast reconstruction (DBR). Breast reconstruction has
been shown to have a positive effect on quality of life postmastectomy. This
retrospective study investigated the impact of the introduction of a dedicated
oncoplastic multidisciplinary meeting (OP MDM) on our unit's breast
reconstruction rate. PATIENTS AND METHODS: A retrospective analysis of 229 women
who underwent mastectomy, of whom 81 (35%) underwent breast reconstruction
between April 2014 and March 2016. Data were analyzed before and after
introduction of OP MDM in April 2015. Data on patient age, type of surgery
(mastectomy only, mastectomy and reconstruction), timing of reconstruction (IBR,
DBR), and type of reconstruction (implant, autologous) were collected. RESULTS:
Between April 2015 and March 2016, following establishment of OP
multidisciplinary team in April 2015, of the 120 patients who had mastectomy, 50
(42%) underwent breast reconstruction with 78% (39/50) choosing IBR (56% implant
reconstruction and 22% autologous). Compared to the period between April 2014 and
March 2015 preceding the OP MDM, of 109 patients who underwent mastectomy, only
31 (28%) had breast reconstruction with 64% (20/31) choosing IBR (45% implant
reconstruction and 19% autologous). The rate of DBR was lower, 22% (11/50),
following OP MDM compared to 35% (11/31) before OP MDM. CONCLUSION: There has
been an increased uptake of breast reconstruction surgery from 28% to 42%. The
biggest impact was on those opting for the immediate type reconstruction option
(78%). The OP MDM has significantly contributed to this increased rate of
reconstruction.
PMID- 28496363
TI - Prognostic value of histone chaperone FACT subunits expression in breast cancer.
AB - Understanding the underlying reasons for tumor aggressiveness, such as why some
tumors grow slowly and locally, while others rapidly progress to a lethal
metastatic disease, is still limited. This is especially critical in breast
cancer (BrCa) due to its high prevalence and also due to the possibility that it
can be detected early. Several oncogenes and tumor suppressors have been
identified and are used in the prognosis and treatment of BrCa. However, even
with these markers, the outcome within BrCa subtypes is highly variable.
Chromatin organization has long been acknowledged as a factor that plays an
important role in tumor progression, but molecular mechanisms defining chromatin
dynamics are largely missing. We have recently found that histone chaperone FACT
(facilitates chromatin transcription) is overexpressed in ~18-20% of BrCa cases.
FACT is elevated upon transformation of mammary epithelial cells and is essential
for viability of tumor cells. BrCa cells with high FACT have a more aggressive
transcriptional program than those with low FACT cells. Based on this we propose
that FACT may be a marker of aggressive BrCa. In this study, we aimed to
comprehensively characterize the pattern of FACT expression in BrCa in relation
to other molecular and clinical prognostic markers. We developed and tested an
assay for the detection and quantitation of protein levels of both FACT subunits,
SSRP1, and SPT16, in clinical samples. We compared the value of mRNA and protein
as potential markers of disease aggressiveness using a large cohort of patients
(n=1092). We demonstrated that only SSRP1 immunohistochemical staining is a
reliable indicator of FACT levels in tumor samples. High SSRP1 correlated with
known markers of poor prognosis, such as negative hormone receptor status,
presence of Her2, high-grade tumors, and tumors of later clinical stage. At the
same time, no strong correlation between SSRP1 expression and survival was
detected when all samples were analyzed together. Clear trend toward longer
survival of patients with low or no SSRP1 expression in tumor samples was seen in
several subgroups of patients, and most importantly significant association of
high SSRP1 expression with shorter disease-free survival was detected in patients
with early-stage and low-grade BrCa, the category of patients with the highest
demand in predictive marker of disease progression.
PMID- 28496364
TI - Oligodendrogliomas in pediatric and adult patients: an outcome-based study from
the Surveillance, Epidemiology, and End Result database.
AB - INTRODUCTION: Oligodendrogliomas (OGs) account for <20% of all intracranial
tumors and 25% of gliomas. Despite improvements in imaging techniques allowing
for earlier diagnosis, OG is rare among the pediatric population. This study
examines a large cohort of OG patients in an effort to define the demographic,
clinical, and pathologic factors associated with clinical and survival outcomes.
METHODS: Data on 7,001 OG patients were abstracted from the Surveillance,
Epidemiology, and End Result (SEER) database (1973-2013). Pediatric patients were
defined as <=19 years old, and adult patients were defined as age >=20 years.
RESULTS: Among 7,001 OG patients, 6.5% were pediatric (mean age 12 +/- 6 years),
and 93.5% were adult (mean age 46 +/- 15 years). Overall, OGs were more common
among males, with a male-to-female ratio of 1.28:1. Overall, OGs were more common
among Caucasians (76.9%) and also among the African American (10.8% pediatric vs.
4.0% adult) and Hispanic (12.8% pediatric vs. 11.8% adult). OGs occurred most
commonly in the temporal lobe of pediatric patients and the frontal lobes of
adults. Surgical resection was the primary treatment modality for both pediatric
and adult populations (70.6% and 40.5%), followed by combined surgery and
radiation (19.7% and 41.2%). Surgical resection was associated with significantly
improved survival in both groups. Pediatric patients had a lower overall
mortality (19.8% vs. 48.5%) and lower cancer-specific mortality (17.6% vs.
36.8%). CONCLUSION: OGs most often present in Caucasian males in their fifth
decade of life with tumors >4 cm in size. Children typically present with tumors
in the temporal lobe, while adults present with tumors in the frontal lobe.
Surgical resection confers a survival advantage among all patients, especially
pediatric patients. Overall survival (OS) and cancer-specific survival are higher
in the pediatric population. Further studies on novel treatment techniques,
including bevacizumab and immunotherapy approaches, are required.
PMID- 28496365
TI - Prevalence and prognosis of stress disorders: a review of the epidemiologic
literature.
AB - Given the ubiquity of traumatic events, it is not surprising that posttraumatic
stress disorder (PTSD) - a common diagnosis following one of these experiences -
is characterized as conferring a large burden for individuals and society.
Although there is recognition of the importance of PTSD diagnoses throughout
psychiatry, the literature on other diagnoses one may receive following a
stressful or traumatic event is scant. This review summarizes the literature on
stress disorders (classified according to the International Classification of
Diseases, 10th Edition [ICD-10]), including acute stress reaction, PTSD,
adjustment disorder and unspecified stress reactions. This review focuses on the
literature related to common psychiatric and somatic consequences of these
disorders. The prevalence and incidence of each disorder are described. A review
of epidemiologic studies on comorbid mental health conditions, including
depression, anxiety and substance abuse, is included, as well as a review of
epidemiologic studies on somatic outcomes, including cancer, cardiovascular
disease and gastrointestinal disorders. Finally, the current literature on all
cause mortality and suicide following stress disorder diagnoses is reviewed.
Stress disorders are a critical public health issue with potentially deleterious
outcomes that have a significant impact on those living with these disorders, the
health care system and society. It is only through an awareness of the impact of
stress disorders that appropriate resources can be allocated to prevention and
treatment. Future research should expand the work done to date beyond the
examination of PTSD, so that the field may obtain a more complete picture of the
impact all stress disorders have on the many people living with these diagnoses.
PMID- 28496366
TI - Factors associated with psychological distress among young women in Kisumu,
Kenya.
AB - BACKGROUND: Attention to mental health issues is growing globally. In many
countries, including Kenya, however, assessment of psychological distress,
especially in rural areas, is limited. METHODS: We analyzed data from young women
screened for a longitudinal contraceptive ring study in Kisumu, Kenya.
Multivariable regression analysis was used to assess factors associated with
recent moderate and high psychological distress, as measured by the Kessler (K-6)
psychological distress scale. RESULTS: Among the 461 women screened, most (58.4%)
were categorized as having moderate psychological distress, 20.8% were
categorized as having low or no psychological distress, and 20.8% were
categorized as having high psychological distress. Moderate psychological
distress (vs low/no) was significantly more likely among women who reported a
history of forced sex and were concerned about recent food insecurity. High (vs
low/no) psychological distress was significantly more likely among women who
reported a history of forced sex, who were concerned about recent food
insecurity, and who self-reported a sexually transmitted infection. CONCLUSION:
To reduce psychological distress, a focus on prevention as well as care methods
is needed. Girls need a path toward a healthy and productive adulthood with a
focus on education, which would help them gain skills to avoid forced sex. Women
would benefit from easy access to social services and supports that would help
them with basic needs like food security among other things. A holistic or
ecological approach to services that would address mental, educational, social,
health, and economic issues may have the highest chance of having a long-term
positive impact on public health.
PMID- 28496367
TI - Radiation-induced vaginal stenosis: current perspectives.
AB - Treatment of gynecological cancer commonly involves pelvic radiation therapy (RT)
and/or brachytherapy. A commonly observed side effect of such treatment is
radiation-induced vaginal stenosis (VS). This review analyzed the incidence,
pathogenesis, clinical manifestation(s) and assessment and grading of radiation
induced VS. In addition, risk factors, prevention and treatment options and
follow-up schedules are also discussed. The limited available literature on many
of these aspects suggests that additional studies are required to more precisely
determine the best management strategy of this prevalent group after RT.
PMID- 28496369
TI - Efficacy and safety of a flexible extended regimen of
ethinylestradiol/drospirenone for the treatment of dysmenorrhea: a multicenter,
randomized, open-label, active-controlled study.
AB - BACKGROUND: Dysmenorrhea is a common condition in women, which is characterized
by menstrual pain. Low-dose estrogen/progestin combined oral contraceptives have
been shown to reduce the severity of dysmenorrhea symptoms, and a 28-day cyclic
regimen of ethinylestradiol/drospirenone (28d regimen) is approved for this
indication in Japan. AIM: The aim of this study was to assess the safety and
efficacy of a flexible extended regimen of ethinylestradiol/drospirenone
(flexible regimen) in Japanese women with dysmenorrhea. METHODS: This
multicenter, open-label study was performed in Japanese women with dysmenorrhea
who, after a baseline observational phase, were randomized to receive
ethinylestradiol 20 MUg/drospirenone 3 mg in a flexible regimen (one tablet each
day for 24-120 days followed by a 4-day tablet-free interval) or in the standard
28d regimen (one tablet each day for 24 days, followed by 4 days of placebo
tablets for six cycles). The primary endpoint was the number of days with
dysmenorrhea of at least mild intensity over a 140-day evaluation period.
Dysmenorrhea scores, bleeding patterns, and other pain-related parameters were
also assessed. RESULTS: A total of 216 women (mean age 29.7 years) were
randomized to the flexible regimen (n=108) or 28d regimen (n=108) and 212 were
included in the full analysis sets (flexible regimen, n=105; 28d regimen, n=107).
Women in the flexible-regimen group reported a mean of 3.4 fewer days with
dysmenorrheic pain than women in the 28d-regimen group, with similar decreases in
disease severity reported in both treatment groups. According to the
investigators, 64.8% and 59.4% of women in the flexible-regimen and 28d-regimen
treatment groups had "very much improved" or "much improved" disease, while 54.3%
and 50.9% of patients reported being "very much satisfied" or "much satisfied"
with their treatment, respectively. CONCLUSION: In Japanese women with
dysmenorrhea, a flexible extended regimen of ethinylestradiol/drospirenone
decreased the number of days with dysmenorrheic pain versus the traditional 28d
regimen.
PMID- 28496370
TI - Trends and causes of maternal mortality in Jimma University Specialized Hospital,
southwest Ethiopia: a matched case-control study.
AB - INTRODUCTION: Measures of maternal death are fundamental to a country's health
and development status. In developing countries, it remains a daunting and
largely unmet public health challenge. There were two studies completed over 10
years ago in Jimma University Specialized Hospital to identify trends, but
recently there have been many changes in Ethiopia to reduce maternal death.
Therefore, it is important to track the achievements made in Ethiopia in the
context of Jimma University Specialized Hospital. No study undertaken in the
country has quantified deaths of women from specific causes after controlling
confounders. OBJECTIVE: To assess trends and causes of maternal death in Jimma
University Specialized Hospital, southwest Ethiopia. METHODS: A time-matched case
control study was conducted on 600 (120 cases and 480 controls) females who
utilized obstetrics and gynecology services from January 2010 to December 2014.
To observe trends in maternal death, maternal mortality ratio was calculated for
each year. Stata version 13 was used to analyze causal inference using propensity
score matching method. RESULTS: Maternal mortality ratio was 857/100,000 and had
a decreasing trend from it's highest in 2010 of 1,873/100,000 to it's lowest of
350/100,000 in 2014. The leading cause of maternal death was hemorrhage (54%)
(beta=0.477, 95% confidence interval [CI]: 0.307, 0.647), followed by pregnancy
induced hypertension (20%) (beta=0.232, 95% CI: 0.046, 0.419), and anemia (12%)
(beta=0.110, 95% CI: 0.017, 0.204). CONCLUSION: There is a decreasing trend of
maternal death. Hemorrhage was the major cause of death identified in each year
of study.
PMID- 28496368
TI - Self-management and psychological-sexological interventions in patients with
endometriosis: strategies, outcomes, and integration into clinical care.
AB - Endometriosis has a multifactorial etiology. The onset and progression of the
disease are believed to be related to different pathogenic mechanisms. Among
them, the environment and lifestyle may play significant roles. Diet, dietary
supplements, physical exercise, osteopathy, massage, acupuncture, transcutaneous
electrical nerve stimulation, and Chinese herbal medicine may represent a
complementary and feasible approach in the treatment of symptoms related to the
disease. In this narrative review, we aimed to examine the most updated evidence
on these alternative approaches implicated in the self-management of the disease.
In addition, several studies have demonstrated that endometriosis may negatively
impact mental health and quality of life, suggesting that affected women may have
an increased risk of developing psychological suffering as well as sexual
problems due to the presence of pain. In light of these findings, we discuss the
importance of integrating psychological interventions (including psychotherapy)
and sexual therapy in endometriosis treatment.
PMID- 28496371
TI - Dyschromatosis symmetrica hereditaria with cutaneous lupus erythematosus and
hyperthyroidism.
AB - Dyschromatosis symmetrica hereditaria (DSH) is a rare genodermatosis
characterized by various sizes of both hyper- and hypopigmented macules arranged
in reticulated patterns on the face and the dorsal aspects of the extremities.
There are also cutaneous and extracutaneous abnormalities, but they are rare. As
far as we know, DSH associated with immune-mediated conditions has not been
reported. We report the first case of DSH, which is associated with cutaneous
lupus erythematosus and hyperthyroidism.
PMID- 28496372
TI - Choroidal extranodal marginal zone lymphoma diagnosed by full-thickness
retinochoroidal biopsy: case report and review of the literature.
AB - The case of an 89-year-old man who was referred for a painless decrease of vision
in his right eye (RE) is reported. Fundus examination of the RE showed an
elevated amelanotic lesion located in the posterior pole with an adjacent focal
round pigmented lesion. There was also a more peripheral amelanotic lesion
extending from 6 to 9 o'clock clockwise inferotemporally. Uveitis workup and
imaging studies of brain and orbits were normal. A retinochoroidal biopsy was
done and showed the presence of choroidal extranodal marginal zone lymphoma. The
patient was treated with external beam radiotherapy. This report presents a
review of the literature of all reported cases of choroidal extranodal marginal
zone lymphoma.
PMID- 28496373
TI - Multimodal images of chronic branch retinal vein occlusion.
AB - Two illustrative cases of chronic branch retinal vein occlusion are presented
with multimodal imaging, including commercially available optical coherence
tomography angiography. In these two patients, retinal ischemia and collateral
vessels were well imaged without the need to use traditional fluorescein
angiography. Optical coherence tomography angiography provides useful information
for the diagnosis and management of patients with branch retinal vein occlusion
and other retinal vascular diseases.
PMID- 28496374
TI - Gender differences and psychological factors associated with suicidal ideation
among youth in Malaysia.
AB - Suicide is a global phenomenon that has been showing an upward trend in recent
years. It is the second leading cause of death among youth. Studies on suicidal
ideation warrant greater attention, as it leads to suicide attempts and other
health risk behaviors. Thus, the objective of this study was to compare gender
differences in suicidal ideation and determine the predictors of suicidal
ideation among youth. This cross-sectional study was carried out among 232 youths
aged between 15 and 25 years from selected urban areas in Malaysia. The results
showed that suicidal ideation was higher among male participants compared with
female participants. Age was the predictor of suicidal ideation for males, while
depression and loss of motivation, as components of hopelessness, were the
predictors of suicidal ideation among females. Hence, it is important that
professionals conduct early identification tests for suicidality among young
people. This will facilitate the early detection of depression and hopelessness,
which is important, in order to prevent suicidal behaviors or other problems
before these occur.
PMID- 28496375
TI - Revisiting the etiological aspects of dissociative identity disorder: a
biopsychosocial perspective.
AB - Dissociative identity disorder (DID) is a chronic post-traumatic disorder where
developmentally stressful events in childhood, including abuse, emotional
neglect, disturbed attachment, and boundary violations are central and typical
etiological factors. Familial, societal, and cultural factors may give rise to
the trauma and/or they may influence the expression of DID. Memory and the
construction of self-identity are cognitive processes that appear markedly and
centrally disrupted in DID and are related to its etiology. Enduring decoupling
of psychological modes may create separate senses of self, and metamemory
processes may be involved in interidentity amnesia. Neurobiological differences
have been demonstrated between dissociative identities within patients with DID
and between patients with DID and controls. Given the current evidence, DID as a
diagnostic entity cannot be explained as a phenomenon created by iatrogenic
influences, suggestibility, malingering, or social role-taking. On the contrary,
DID is an empirically robust chronic psychiatric disorder based on
neurobiological, cognitive, and interpersonal non-integration as a response to
unbearable stress. While current evidence is sufficient to firmly establish this
etiological stance, given the wide opportunities for innovative research, the
disorder is still understudied. Comparison of well-selected samples of DID
patients with non-dissociative subjects who have other psychiatric disorders
would further delineate the neurobiological and cognitive features of the
disorder, whereas genetic research on DID would further illuminate the
interaction of the individual with environmental stress. As such, DID may be seen
as an exemplary disease model of the biopsychosocial paradigm in psychiatry.
PMID- 28496376
TI - Changing trends in residents-as-teachers across graduate medical education.
AB - BACKGROUND: Teaching residents how to teach is a critical part of residents'
training in graduate medical education (GME). The purpose of this study was to
assess the change in resident-as-teacher (RaT) instruction in GME over the past
15 years in the US. METHODS: We used a quantitative and qualitative survey of all
program directors (PDs) across specialties. We compared our findings with a
previous work from 2000-2001 that studied the same matter. Finally, we
qualitatively analyzed PDs' responses regarding the reasons for implementing and
not implementing RaT instruction. RESULTS: Two hundred and twenty-one PDs
completed the survey, which yields a response rate of 12.6%. Over 80% of PDs
implement RaT, an increase of 26.34% compared to 2000-2001. RaT instruction uses
multiple methods with didactic lectures reported as the most common, followed by
role playing in simulated environments, then observing and giving feedback.
Residents giving feedback, clinical supervision, and bedside teaching were the
top three targeted skills. Through our qualitative analysis we identified five
main reasons for implementing RaT: teaching is part of the residents' role;
learners desire formal RaT training; regulatory bodies require RaT training; RaT
improves residents' education; and RaT prepares residents for their current and
future roles. CONCLUSION: The use of RaT instruction has increased significantly
in GME. More and more PDs are realizing its importance in the residents'
formative training experience. Future studies should examine the effectiveness of
each method for RaT instruction.
PMID- 28496377
TI - Advances in medical education and practice: student perceptions of the flipped
classroom.
PMID- 28496378
TI - Ethnopsychiatry fosters creativity and the adoption of critical and reflexive
thinking in higher education students: insights from a qualitative analysis of a
preliminary pilot experience at the Faculty of Medicine and Surgery, University
of Genoa, Italy.
AB - Creativity is an ability that plays a major role in the modern economy and
society. It should represent an important component of the medical syllabus.
However, it is often overlooked by the formal courses at universities. The
current study aimed at evaluating whether the interactive educational models,
recently adopted by the Faculty of Medicine and Surgery, at the University of
Genoa, Italy, would favor the adoption of critical thinking, attitudes to
changes, cultural diversity acceptance, and the adoption of relational soft
skills versus traditional and frontal didactic teaching. Thirty students, who
attended the last year of health care professional course at the Faculty of
Medicine, volunteered to take part in the study and were randomly allocated to
two groups: one group receiving an innovative, interactive excellence course and
the other group receiving a more traditional approach. Ethnopsychiatry was chosen
as the topic since it was hypothesized that it would have contributed to
generation of a new approach toward diseases and patients. The first group of
students, exposed to interactive lectures with the aim of promoting the adoption
of critical thinking, were more satisfied than the second group. Participants who
were involved in an active manner and had to work in small groups, actively
finding their own solutions to solve the problems, perceived the utilized
teaching method and experience more stimulating, involving, and effective.
Implications for education policy makers are also envisaged.
PMID- 28496379
TI - Self-organization of Nucleic Acids in Lipid Constructs.
AB - Lipids and nucleic acids (NAs) can hierarchically self-organize into a variety of
nanostructures of increasingly complex geometries such as the 1D lamellar, 2D
hexagonal, and 3D bicontinuous cubic phases. The diversity and complexity of
those lipid-NA assemblies are interesting from a fundamental perspective as well
as being relevant to the performance in gene delivery and gene silencing
applications. The finding that not only the chemical make of the lipid-NA
constructs, but their actual supramolecular organization, affects their gene
transfection and silencing efficiencies has inspired physicists, chemists, and
engineers to this field of research. At the moment it remains an open question
how exactly the different lipid-NA structures interact with cells and organelles
in order to output an optimal response. This article reviews our current
understanding of the structures of different lipid-NA complexes and the
corresponding cellular interaction mechanisms. The recent advances in designing
optimal lipid-based NA carriers will be introduced with an emphasis on the
structure-function relations.
PMID- 28496380
TI - Use of the PIXEL method to investigate gas adsorption in metal-organic
frameworks.
AB - PIXEL has been used to perform calculations of adsorbate-adsorbent interaction
energies between a range of metal-organic frameworks (MOFs) and simple guest
molecules. Interactions have been calculated for adsorption between MOF-5 and Ar,
H2, and N2; Zn2(BDC)2(TED) (BDC = 1,4-benzenedicarboxylic acid, TED =
triethylenediamine) and H2; and HKUST-1 and CO2. The locations of the adsorption
sites and the calculated energies, which show differences in the Coulombic or
dispersion characteristic of the interaction, compare favourably to experimental
data and literature energy values calculated using density functional theory.
PMID- 28496381
TI - Hydrophilic Pt nanoflowers: synthesis, crystallographic analysis and catalytic
performance.
AB - Water-soluble Pt nanoflowers (NFs) were prepared by diethylene glycol-mediated
reduction of Pt acetylacetonate (Pt(acac)2) in the presence of polyethylenimine.
Advanced electron microscopy analysis showed that the NFs consist of multiple
branches with a truncated cubic morphology and different crystallographic
orientations. We demonstrate that the nature of the solvent strongly influences
the resulting morphology. The catalytic performance of the Pt NFs in 4
nitrophenol reduction was found to be superior to that of other nanoparticle
based catalysts. Additionally, the Pt NFs display good catalytic reusability with
no loss of activity after five consecutive cycles.
PMID- 28496383
TI - Renata S. Maricevich, MD, and Tuan A. Truong, MD.
PMID- 28496382
TI - Elements of Family-Centered Care in the Pediatric Intensive Care Unit: An
Integrative Review.
AB - This paper reports result from a systematic search and thematic analysis of
qualitative literature to identify key issues related to family-centered care,
behaviors, and communication skills that support the parental role and improve
patient and family outcomes in the PICU. Five themes were identified: 1) sharing
information; 2) hearing parental voices; 3) making decisions for or with parents;
4) negotiating roles; and 5) individualizing communication. These themes
highlight several gaps between how parents want to be involved and perceive
clinicians engage them in the care of their child. Parental preferences for
involvement differ in the domains of information sharing, decision making, and
power-sharing across a spectrum of parental roles from parents as care provider
to care recipient. The PICU setting may place clinicians in a double bind trying
to both engage families and protect them from distress. Asking families of
critically ill children about their preferences for participation across these
domains may improve clinician-family relationships.
PMID- 28496384
TI - Facial Trauma.
PMID- 28496385
TI - Initial Assessment and Evaluation of Traumatic Facial Injuries.
AB - The care of the facial trauma patient continues to evolve in the ever-changing
face of medicine. Patients can be reassured that their care is managed by a
variety of specialists knowledgeable in the assessment and management of complex
facial injuries. Thanks in part to advances in imaging modalities, bone fixation
techniques and technology, and a wider array of reconstructive procedures, the
foundation upon which the reconstructive ladder of facial injuries rests
continues to expand. The overall goal of repair is a return to a preinjury state
of form and function.
PMID- 28496386
TI - Soft Tissue Management in Facial Trauma.
AB - The management of soft tissue injury after facial trauma poses unique challenges
to the plastic surgeon, given the specialized nature of facial tissue and the
aesthetic importance of the face. The general principles of trauma management and
wound care are applied in all cases. The management of severe injuries to the
face is discussed in relation to the location and the mechanism of injury. Facial
transplants have arisen in the past decade for the management of catastrophic
soft tissue defects, although high morbidity and mortality after these non-life
saving operations must be considered in patient selection.
PMID- 28496387
TI - Frontal Sinus Fractures.
AB - The frontal bone serves a protective role, representing the transition between
the facial skeleton and the cranium. Within its enclosure, the frontal sinus lies
adjacent to many important intracranial structures, and injury to this region has
severe complications if not properly managed. Historically, the goals of frontal
sinus fracture management have been to best prevent intracranial complications
with invasive procedures, but a recent shift favoring conservative management now
aims to preserve the form and function of the frontal sinus and its outflow
tract. With the advancement of endoscopic techniques and the development of new
technologies, many alternatives to aggressive surgical management are available.
PMID- 28496388
TI - Midface Fractures I.
AB - Facial fractures are a common source of emergency department consultations for
the plastic surgeon. A working understanding of evaluation, assessment,
management, and prevention of further injury when dealing with these fractures is
vital. This two-part series detailing the management of midface fractures serves
as a guide for the appropriate workup and management of the wide variety of
fracture patterns that are commonly encountered.
PMID- 28496389
TI - Midface Fractures II.
AB - Facial fractures are a common source of emergency department consultations for
the plastic surgeon. A working understanding of the evaluation, the assessment,
the management, and the prevention of further injury when dealing with these
fractures is vital. This second of a two-part series detailing the management of
midfacial fractures serves as a guide for the appropriate workup and management
of the wide variety of fracture patterns that are commonly encountered.
PMID- 28496391
TI - Management of Panfacial Fracture.
AB - Traumatic panfacial fracture repair is one of the most complex and challenging
reconstructive procedures to perform. Several principles permeate throughout
literature regarding the repair of panfacial injuries in a stepwise fashion. The
primary goal of management in most of these approaches is to restore the occlusal
relationship at the beginning of sequential repair so that other structures can
fall into alignment. Through proper positioning of the occlusion and the
mandibular-maxillary unit with the skull base, the spatial relationships and
stability of midface buttresses and pillars can then be re-established. Here, the
authors outline the sequencing of panfacial fracture repair for the restoration
of anatomical relationships and the optimization of functional and structural
outcomes.
PMID- 28496392
TI - Differences in the Management of Pediatric Facial Trauma.
AB - Craniofacial trauma is common in the pediatric population, with most cases
limited to soft tissue and dentoalveolar injury. Although facial fractures are
relatively rare in children compared with adults, they are often associated with
severe injury and cause significant morbidity and disability. Initial evaluation
of a child with facial trauma generally involves stabilizing the patient and
identifying any severe concomitant injuries before diagnosing and managing facial
injuries. The management of pediatric facial fractures is relatively more
conservative than that of adults, and nonsurgical management is preferred when
possible to prevent the disruption of future growth and development. Outcomes
depend on the site of the injury, management plan, and subsequent growth, so
children must be followed longitudinally for monitoring and the identification of
any complications.
PMID- 28496390
TI - Mandible Fractures.
AB - Mandible fractures account for a significant portion of maxillofacial injuries
and the evaluation, diagnosis, and management of these fractures remain
challenging despite improved imaging technology and fixation techniques.
Understanding appropriate surgical management can prevent complications such as
malocclusion, pain, and revision procedures. Depending on the type and location
of the fractures, various open and closed surgical reduction techniques can be
utilized. In this article, the authors review the diagnostic evaluation,
treatment options, and common complications of mandible fractures. Special
considerations are described for pediatric and atrophic mandibles.
PMID- 28496393
TI - Subtlety of Ambient-Language Effects in Babbling: A Study of English- and Chinese
Learning Infants at 8, 10, and 12 Months.
AB - Prior research on ambient-language effects in babbling has often suggested
infants produce language-specific phonological features within the first year.
These results have been questioned in research failing to find such effects and
challenging the positive findings on methodological grounds. We studied English-
and Chinese-learning infants at 8, 10, and 12 months and found listeners could
not detect ambient-language effects in the vast majority of infant utterances,
but only in items deemed to be words or to contain canonical syllables that may
have made them sound like words with language-specific shapes. Thus, the present
research suggests the earliest ambient-language effects may be found in emerging
lexical items or in utterances influenced by language-specific features of
lexical items. Even the ambient-language effects for infant canonical syllables
and words were very small compared with ambient-language effects for meaningless
but phonotactically well-formed syllable sequences spoken by adult native
speakers of English and Chinese.
PMID- 28496394
TI - Triazaspirocycles: Occurrence, Synthesis, and Applications.
AB - Natural products bearing a triazaspirocyclic motif have received significant
attention in recent years. These compounds, which feature three nitrogen atoms
attached to one quaternary carbon forming a spirocyclic scaffold, exhibit a wide
range of biological activity and have promising applications in materials as well
as in drug discovery. In this review article, we will discuss triazaspirocycles
in Nature, their biological activity, and applications. Methods for the synthesis
of triazaspirocycles as well as the reactivity of triazaspirocyclic scaffolds
will be reviewed.
PMID- 28496395
TI - A relative quantitative positive/negative ion switching method for untargeted
lipidomics via high resolution LC-MS/MS from any biological source.
AB - INTRODUCTION: Advances in high-resolution mass spectrometry have created renewed
interest for studying global lipid biochemistry in disease and biological
systems. OBJECTIVES: Here, we present an untargeted 30 min. LC-MS/MS platform
that utilizes positive/negative polarity switching to perform unbiased data
dependent acquisitions (DDA) via higher energy collisional dissociation (HCD)
fragmentation to profile more than 1000-1500 lipid ions mainly from methyl-tert
butyl ether (MTBE) or chloroform:methanol extractions. METHODS: The platform uses
C18 reversed-phase chromatography coupled to a hybrid QExactive Plus/HF Orbitrap
mass spectrometer and the entire procedure takes ~10 h from lipid extraction to
identification/quantification for a data set containing 12 samples (~4 h for a
single sample). Lipids are identified by both accurate precursor ion mass and
fragmentation features and quantified using Lipid-Search and Elements software.
RESULTS: Using this approach, we are able to profile intact lipid ions from up to
18 different main lipid classes and 66 subclasses. We show several studies from
different biological sources, including cultured cancer cells, resected tissues
from mice such as lung and breast tumors and biological fluids such as plasma and
urine. CONCLUSIONS: Using mouse embryonic fibroblasts, we showed that TSC2-/- KD
significantly abrogates lipid biosynthesis and that rapamycin can rescue
triglyceride (TG) lipids and we show that SREBP-/- shuts down lipid biosynthesis
significantly via mTORC1 signaling pathways. We show that in mouse EGFR driven
lung tumors, a large number of TGs and phosphatidylmethanol (PMe) lipids are
elevated while some phospholipids (PLs) show some of the largest decrease in
lipid levels from ~ 2000 identified lipid ions. In addition, we identified more
than 1500 unique lipid species from human blood plasma.
PMID- 28496396
TI - Interventions for reducing self-stigma in people with mental illnesses: a
systematic review of randomized controlled trials.
AB - Background: Self-stigma occurs when people with mental illnesses internalize
negative stereotypes and prejudices about their condition. It can reduce help
seeking behaviour and treatment adherence. The effectiveness of interventions
aimed at reducing self-stigma in people with mental illness is systematically
reviewed. Results are discussed in the context of a logic model of the broader
social context of mental illness stigma. Methods: Medline, Embase, PsycINFO,
ERIC, and CENTRAL were searched for randomized controlled trials in November
2013. Studies were assessed with the Cochrane risk of bias tool. Results: Five
trials were eligible for inclusion, four of which provided data for statistical
analyses. Four studies had a high risk of bias. The quality of evidence was very
low for each set of interventions and outcomes. The interventions studied
included various group based anti-stigma interventions and an anti-stigma
booklet. The intensity and fidelity of most interventions was high. Two studies
were considered to be sufficiently homogeneous to be pooled for the outcome self
stigma. The meta-analysis did not find a statistically significant effect (SMD
[95% CI] at 3 months: -0.26 [-0.64, 0.12], I2=0%, n=108). None of the individual
studies found sustainable effects on other outcomes, including recovery, help
seeking behaviour and self-stigma. Conclusions: The effectiveness of
interventions against self-stigma is uncertain. Previous studies lacked
statistical power, used questionable outcome measures and had a high risk of
bias. Future studies should be based on robust methods and consider practical
implications regarding intervention development (relevance, implementability, and
placement in routine services).
PMID- 28496397
TI - Conflicts at work are associated with a higher risk of cardiovascular disease.
AB - Background: Only few authors have analyzed the impact of workplace conflicts and
the resulting stress on the risk of developing cardiovascular disorders. The goal
of this study was to analyze the association between workplace conflicts and
cardiovascular disorders in patients treated by German general practitioners.
Methods: Patients with an initial documentation of a workplace conflict
experience between 2005 and 2014 were identified in 699 general practitioner
practices (index date). We included only those who were between the ages of 18
and 65 years, had a follow-up time of at least 180 days after the index date, and
had not been diagnosed with angina pectoris, myocardial infarction, coronary
heart diseases, or stroke prior to the documentation of the workplace mobbing. In
total, the study population consisted of 7,374 patients who experienced conflicts
and 7,374 controls for analysis. The main outcome measure was the incidence of
angina pectoris, myocardial infarction, and stroke correlated with workplace
conflict experiences. Results: After a maximum of five years of follow-up, 2.9%
of individuals who experienced workplace conflict were affected by cardiovascular
diseases, while only 1.4% were affected in the control group (p-value <0.001).
Workplace conflict was associated with a 1.63-fold increase in the risk of
developing cardiovascular diseases. Finally, the impact of workplace conflict was
higher for myocardial infarction (OR=2.03) than for angina pectoris (OR=1.79) and
stroke (OR=1.56). Conclusions: Overall, we found a significant association
between workplace conflicts and cardiovascular disorders.
PMID- 28496399
TI - The Effect of Wealth Shocks on Loss Aversion: Behavior and Neural Correlates.
AB - Kahneman and Tversky (1979) first demonstrated that when individuals decide
whether or not to accept a gamble, potential losses receive more weight than
possible gains in the decision. This phenomenon is referred to as loss aversion.
We investigated how loss aversion in risky financial decisions is influenced by
sudden changes to wealth, employing both behavioral and neurobiological measures.
We implemented an fMRI experimental paradigm, based on that employed by Tom et
al. (2007). There are two treatments, called RANDOM and CONTINGENT. In RANDOM,
the baseline setting, the changes to wealth, referred to as wealth shocks in
economics, are independent of the actual choices participants make. Under
CONTINGENT, we induce the belief that the changes in income are a consequence of
subjects' own decisions. The magnitudes and sequence of the shocks to wealth are
identical between the CONTINGENT and RANDOM treatments. We investigated whether
more loss aversion existed in one treatment than another. The behavioral results
showed significantly greater loss aversion in CONTINGENT compared to RANDOM after
a negative wealth shock. No differences were observed in the response to positive
shocks. The fMRI results revealed a neural loss aversion network, comprising the
bilateral striatum, amygdala and dorsal anterior cingulate cortex that was common
to the CONTINGENT and RANDOM tasks. However, the ventral prefrontal cortex,
primary somatosensory cortex and superior occipital cortex, showed greater
activation in response to a negative change in wealth due to individual's own
decisions than when the change was exogenous. These results indicate that
striatum activation correlates with loss aversion independently of the source of
the shock, and that the ventral prefrontal cortex (vPFC) codes the experimental
manipulation of agency in one's actions influencing loss aversion.
PMID- 28496398
TI - Growth of Thalamocortical Fibers to the Somatosensory Cortex in the Human Fetal
Brain.
AB - Thalamocortical (TH-C) fiber growth begins during the embryonic period and is
completed by the third trimester of gestation in humans. Here we determined the
timing and trajectories of somatosensory TH-C fibers in the developing human
brain. We analyzed the periods of TH-C fiber outgrowth, path-finding, "waiting"
in the subplate (SP), target selection, and ingrowth in the cortical plate (CP)
using histological sections from post-mortem fetal brain [from 7 to 34
postconceptional weeks (PCW)] that were processed with acetylcholinesterase
(AChE) histochemistry and immunohistochemical methods. Images were compared with
post mortem diffusion tensor imaging (DTI)-based fiber tractography (code No NO1
HD-4-3368). The results showed TH-C axon outgrowth occurs as early as 7.5 PCW in
the ventrolateral part of the thalamic anlage. Between 8 and 9.5 PCW, TH-C axons
form massive bundles that traverse the diencephalic-telencephalic boundary. From
9.5 to 11 PCW, thalamocortical axons pass the periventricular area at the pallial
subpallial boundary and enter intermediate zone in radiating fashion. Between 12
and 14 PCW, the TH-C axons, aligned along the fibers from the basal forebrain,
continue to grow for a short distance within the deep intermediate zone and enter
the deep CP, parallel with SP expansion. Between 14 and 18 PCW, the TH-C
interdigitate with callosal fibers, running shortly in the sagittal stratum and
spreading through the deep SP ("waiting" phase). From 19 to 22 PCW, TH-C axons
accumulate in the superficial SP below the somatosensory cortical area; this
occurs 2 weeks earlier than in the frontal and occipital cortices. Between 23 and
24 PCW, AChE-reactive TH-C axons penetrate the CP concomitantly with its initial
lamination. Between 25 and 34 PCW, AChE reactivity of the CP exhibits an uneven
pattern suggestive of vertical banding, showing a basic 6-layer pattern. In
conclusion, human thalamocortical axons show prolonged growth (4 months), and
somatosensory fibers precede the ingrowth of fibers destined for frontal and
occipital areas. The major features of growing TH-C somatosensory fiber
trajectories are fan-like radiation, short runs in the sagittal strata, and
interdigitation with the callosal system. These results support our hypothesis
that TH-C axons are early factors in SP and CP morphogenesis and synaptogenesis
and may regulate cortical somatosensory system maturation.
PMID- 28496400
TI - LRP1 Modulates APP Intraneuronal Transport and Processing in Its Monomeric and
Dimeric State.
AB - The low-density lipoprotein receptor-related protein 1, LRP1, interacts with APP
and affects its processing. This is assumed to be mostly caused by the impact of
LRP1 on APP endocytosis. More recently, also an interaction of APP and LRP1 early
in the secretory pathway was reported whereat retention of LRP1 in the ER leads
to decreased APP cell surface levels and in turn, to reduced Abeta secretion.
Here, we extended the biochemical and immunocytochemical analyses by showing via
live cell imaging analyses in primary neurons that LRP1 and APP are transported
only partly in common (one third) but to a higher degree in distinct fast axonal
transport vesicles. Interestingly, co-expression of LRP1 and APP caused a change
of APP transport velocities, indicating that LRP1 recruits APP to a specific type
of fast axonal transport vesicles. In contrast lowered levels of LRP1 facilitated
APP transport. We further show that monomeric and dimeric APP exhibit similar
transport characteristics and that both are affected by LRP1 in a similar way, by
slowing down APP anterograde transport and increasing its endocytosis rate. In
line with this, a knockout of LRP1 in CHO cells and in primary neurons caused an
increase of monomeric and dimeric APP surface localization and in turn
accelerated shedding by meprin beta and ADAM10. Notably, a choroid plexus
specific LRP1 knockout caused a much higher secretion of sAPP dimers into the
cerebrospinal fluid compared to sAPP monomers. Together, our data show that LRP1
functions as a sorting receptor for APP, regulating its cell surface localization
and thereby its processing by ADAM10 and meprin beta, with the latter exhibiting
a preference for APP in its dimeric state.
PMID- 28496401
TI - Monitoring the Right Collection: The Central Cholinergic Neurons as an
Instructive Example.
AB - Some neurons are more equal than others: neuroscience relies heavily on the
notion that there is a division of labor among different subtypes of brain cells.
Therefore, it is important to recognize groups of neurons that participate in the
same computation or share similar tasks. However, what the best ways are to
identify such collections is not yet clear. Here, we argue that monitoring the
activity of genetically defined cell types will lead to new insights about neural
mechanisms and improve our understanding of disease vulnerability. Through
highlighting how central cholinergic neurons encode reward and punishment that
can be captured by a unified framework of reinforcement surprise, we hope to
provide an instructive example of how studying a genetically defined cell type
may further our understanding of neural function.
PMID- 28496403
TI - Hysteresis in Center of Mass Velocity Control during the Stance Phase of
Treadmill Walking.
AB - Achieving a soft landing during walking can be quantified by analyzing changes in
the vertical velocity of the body center of mass (CoM) just prior to the landing
of the swing limb. Previous research suggests that walking speed and step length
may predictably influence the extent of this CoM control. Here we ask how stable
this control is. We altered treadmill walking speed by systematically increasing
or decreasing it at fixed intervals. We then reversed direction. We hypothesized
that the control of the CoM vertical velocity during the late stance of the
walking gait may serve as an order parameter which has an attribute of
hysteresis. The presence of hysteresis implies that the CoM control is not based
on simply knowing the current input conditions to predict the output response.
Instead, there is also the influence of previous speed conditions on the ongoing
responses. We found that the magnitudes of CoM control were different depending
on whether the treadmill speed (as the control parameter) was ramped up or down.
Changes in step length also influenced CoM control. A stronger effect was
observed when the treadmill speed was speeded up compared to down. However, the
effect of speed direction remained significant after controlling for step length.
The hysteresis effect of CoM control as a function of speed history demonstrated
in the current study suggests that the regulation of CoM vertical velocity during
late stance is influenced by previous external conditions and constraints which
combine to influence the desired behavioral outcome.
PMID- 28496404
TI - GABA Concentrations in the Anterior Cingulate Cortex Are Associated with Fear
Network Function and Fear Recovery in Humans.
AB - Relapse of fear after successful treatment is a common phenomenon in patients
with anxiety disorders. Animal research suggests that the inhibitory
neurotransmitter gamma-aminobutyric acid (GABA) plays a key role in the
maintenance of extinguished fear. Here, we combined magnetic resonance
spectroscopy and functional magnetic resonance imaging to investigate the role of
GABA in fear recovery in 70 healthy male participants. We associated baseline
GABA levels in the dorsal anterior cingulate cortex (dACC) to indices of fear
recovery as defined by changes in skin conductance responses (SCRs), blood oxygen
level dependent responses, and functional connectivity from fear extinction to
fear retrieval. The results showed that high GABA levels were associated with
increased SCRs, enhanced activation of the right amygdala, and reduced amygdala
ventromedial prefrontal cortex connectivity during fear recovery. Follow-up
analyses exclusively for the extinction phase showed that high GABA levels were
associated with reduced amygdala activation and enhanced amygdala-ventromedial
prefrontal cortex connectivity, despite the absence of correlations between GABA
and physiological responses. Follow-up analyses for the retrieval phase did not
show any significant associations with GABA. Together, the association between
GABA and increases in SCRs from extinction to retrieval, without associations
during both phases separately, suggests that dACC GABA primarily inhibits the
consolidation of fear extinction. In addition, the opposite effects of GABA on
amygdala activity and connectivity during fear extinction compared to fear
recovery suggest that dACC GABA may initially facilitate extinction learning.
PMID- 28496402
TI - Cortico-Striatal-Thalamic Loop Circuits of the Orbitofrontal Cortex: Promising
Therapeutic Targets in Psychiatric Illness.
AB - Corticostriatal circuits through the orbitofrontal cortex (OFC) play key roles in
complex human behaviors such as evaluation, affect regulation and reward-based
decision-making. Importantly, the medial and lateral OFC (mOFC and lOFC) circuits
have functionally and anatomically distinct connectivity profiles which
differentially contribute to the various aspects of goal-directed behavior. OFC
corticostriatal circuits have been consistently implicated across a wide range of
psychiatric disorders, including major depressive disorder (MDD), obsessive
compulsive disorder (OCD), and substance use disorders (SUDs). Furthermore,
psychiatric disorders related to OFC corticostriatal dysfunction can be addressed
via conventional and novel neurostimulatory techniques, including deep brain
stimulation (DBS), electroconvulsive therapy (ECT), repetitive transcranial
magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS).
Such techniques elicit changes in OFC corticostriatal activity, resulting in
changes in clinical symptomatology. Here we review the available literature
regarding how disturbances in mOFC and lOFC corticostriatal functioning may lead
to psychiatric symptomatology in the aforementioned disorders, and how
psychiatric treatments may exert their therapeutic effect by rectifying abnormal
OFC corticostriatal activity. First, we review the role of OFC corticostriatal
circuits in reward-guided learning, decision-making, affect regulation and
reappraisal. Second, we discuss the role of OFC corticostriatal circuit
dysfunction across a wide range of psychiatric disorders. Third, we review
available evidence that the therapeutic mechanisms of various neuromodulation
techniques may directly involve rectifying abnormal activity in mOFC and lOFC
corticostriatal circuits. Finally, we examine the potential of future
applications of therapeutic brain stimulation targeted at OFC circuitry;
specifically, the role of OFC brain stimulation in the growing field of
individually-tailored therapies and personalized medicine in psychiatry.
PMID- 28496406
TI - Neural Correlates of Phrase Rhythm: An EEG Study of Bipartite vs. Rondo Sonata
Form.
AB - This paper introduces the neural correlates of phrase rhythm. In short, phrase
rhythm is the rhythmic aspect of phrase construction and the relationships
between phrases. For the sake of establishing the neural correlates, a musical
experiment has been designed to induce music-evoked stimuli related to phrase
rhythm. Brain activity is monitored through electroencephalography (EEG) by using
a brain-computer interface. The power spectral value of each EEG channel is
estimated to obtain how power variance distributes as a function of frequency.
Our experiment shows statistical differences in theta and alpha bands in the
phrase rhythm variations of two classical sonatas, one in bipartite form and the
other in rondo form.
PMID- 28496405
TI - Temporal Dynamics of Proactive and Reactive Motor Inhibition.
AB - Proactive motor inhibition refers to endogenous preparatory mechanisms
facilitating action inhibition, whereas reactive motor inhibition is considered
to be a sudden stopping process triggered by external signals. Previous studies
were inconclusive about the temporal dynamics of involved neurocognitive
processes during proactive and reactive motor control. Using
electroencephalography (EEG), we investigated the time-course of proactive and
reactive inhibition, measuring event-related oscillations and event-related
potentials (ERPs). Participants performed in a cued go/nogo paradigm with cues
indicating whether the motor response might or might not have to be inhibited.
Based on the dual mechanisms of control (DMC) framework by Braver, we
investigated the role of attentional effects, motor preparation in the
sensorimotor cortex and prefrontal cognitive control mechanisms, separating
effects before and after target onset. In the cue-target interval, proactive
motor inhibition was associated with increased attention, reflected in reduced
visual alpha power and an increased contingent negative variation (CNV). At the
same time, motor inhibition was modulated by reduced sensorimotor beta power.
After target onset, proactive inhibition resulted in an increased N1, indicating
allocation of attention towards relevant stimuli, increased prefrontal beta power
and a modulation of sensorimotor mu activity. As in previous studies, reactive
stopping of motor actions was associated with increased prefrontal beta power and
increased sensorimotor beta activity. The results stress the relevance of
attentional mechanisms for proactive inhibition and speak for different
neurocognitive mechanisms being involved in the early preparation for and in
later implementation of motor inhibition.
PMID- 28496407
TI - Unsupervised Idealization of Ion Channel Recordings by Minimum Description
Length: Application to Human PIEZO1-Channels.
AB - Researchers can investigate the mechanistic and molecular basis of many
physiological phenomena in cells by analyzing the fundamental properties of
single ion channels. These analyses entail recording single channel currents and
measuring current amplitudes and transition rates between conductance states.
Since most electrophysiological recordings contain noise, the data analysis can
proceed by idealizing the recordings to isolate the true currents from the noise.
This de-noising can be accomplished with threshold crossing algorithms and Hidden
Markov Models, but such procedures generally depend on inputs and supervision by
the user, thus requiring some prior knowledge of underlying processes. Channels
with unknown gating and/or functional sub-states and the presence in the
recording of currents from uncorrelated background channels present substantial
challenges to such analyses. Here we describe and characterize an idealization
algorithm based on Rissanen's Minimum Description Length (MDL) Principle. This
method uses minimal assumptions and idealizes ion channel recordings without
requiring a detailed user input or a priori assumptions about channel conductance
and kinetics. Furthermore, we demonstrate that correlation analysis of
conductance steps can resolve properties of single ion channels in recordings
contaminated by signals from multiple channels. We first validated our methods on
simulated data defined with a range of different signal-to-noise levels, and then
showed that our algorithm can recover channel currents and their substates from
recordings with multiple channels, even under conditions of high noise. We then
tested the MDL algorithm on real experimental data from human PIEZO1 channels and
found that our method revealed the presence of substates with alternate
conductances.
PMID- 28496409
TI - Rapid Screening for alpha-Glucosidase Inhibitors from Gymnema sylvestre by
Affinity Ultrafiltration-HPLC-MS.
AB - Gymnema sylvestre R. Br. (Asclepiadaceae) has been known to posses potential anti
diabetic activity, and the gymnemic acids were reported as the main bioactive
components in this plant species. However, the specific components responsible
for the hypoglycemic effect still remain unknown. In the present study, the in
vitro study revealed that the extract of G. sylvestre exhibited significant
inhibitory activity against alpha-glucosidase with IC50 at 68.70 +/- 1.22 MUg/mL
compared to acarbose (positive control) at 59.03 +/- 2.30 MUg/mL, which further
indicated the potential anti-diabetic activity. To this end, a method based on
affinity ultrafiltration coupled with liquid chromatography mass spectrometry (UF
HPLC-MS) was established to rapidly screen and identify the alpha-glucosidase
inhibitors from G. sylvestre. In this way, 9 compounds with higher enrichment
factors (EFs) were identified according to their MS/MS spectra. Finally, the
structure-activity relationships revealed that glycosylation could decrease the
potential antisweet activity of sapogenins, and other components except gymnemic
acids in G. sylvestre could also be good alpha-glucosidase inhibitors due to
their synergistic effects. Taken together, the proposed method combing alpha
glucosidase and UF-HPLC-MS presents high efficiency for rapidly screening and
identifying potential inhibitors of alpha-glucosidase from complex natural
products, and could be further explored as a valuable high-throughput screening
(HTS) platform in the early anti-diabetic drug discovery stage.
PMID- 28496408
TI - The Impact of Microbiota-Gut-Brain Axis on Diabetic Cognition Impairment.
AB - Progressive cognitive dysfunction is a central characteristic of diabetic
encephalopathy (DE). With an aging population, the incidence of DE is rising and
it has become a major threat that seriously affects public health. Studies within
this decade have indicated the important role of risk factors such as oxidative
stress and inflammation on the development of cognitive impairment. With the
recognition of the two-way communication between gut and brain, recent
investigation suggests that "microbiota-gut-brain axis" also plays a pivotal role
in modulating both cognition function and endocrine stability. This review aims
to systemically elucidate the underlying impact of diabetes on cognitive
impairment.
PMID- 28496410
TI - Clinical Applications of Iso-Inertial, Eccentric-Overload (YoYoTM) Resistance
Exercise.
AB - In the quest for a viable non-gravity dependent method to "lift weights" in
space, our laboratory introduced iso-inertial resistance (YoYoTM) exercise using
spinning flywheel(s), more than 25 years ago. After being thoroughly tested in
individuals subjected to various established spaceflight analogs, a multi-mode
YoYoTM exercise apparatus was eventually installed on the International Space
Station in 2009. The method, applicable to any muscle group, provides
accommodated resistance and optimal muscle loading through the full range of
motion of concentric actions, and brief episodes of eccentric overload. This
exercise intervention has found terrestrial applications and shown success in
enhancing sports performance and preventing injury and aiding neurological or
orthopedic rehabilitation. Research has proven that this technique offers unique
physiological responses not possible with other exercise hardware solutions. This
paper provides a brief overview of research that has made use, and explored the
efficacy, of this method in healthy sedentary or physically active individuals
and populations suffering from muscle wasting, disease or injury. While the
collective evidence to date suggests YoYoTM offers a potent stimulus to optimize
the benefits of resistance exercise, systematic research to support clinical use
of this method has only begun to emerge. Thus, we also offer perspectives on
unresolved issues, unexplored applications for clinical conditions, and how this
particular exercise paradigm could be implemented in future clinical research and
eventually being prescribed. Fields of particular interest are those aimed at
promoting muscle health by preventing injury or combating muscle wasting and
neurological or metabolic dysfunction due to aging or illness, or those serving
in rehabilitation following trauma and/or surgery.
PMID- 28496411
TI - Calf Compression Sleeves Change Biomechanics but Not Performance and
Physiological Responses in Trail Running.
AB - Introduction: The aim of this study was to determine whether calf compression
sleeves (CS) affects physiological and biomechanical parameters, exercise
performance, and perceived sensations of muscle fatigue, pain and soreness during
prolonged (~2 h 30 min) outdoor trail running. Methods: Fourteen healthy trained
males took part in a randomized, cross-over study consisting in two identical 24
km trail running sessions (each including one bout of running at constant rate on
moderately flat terrain, and one period of all-out running on hilly terrain)
wearing either degressive CS (23 +/- 2 mmHg) or control sleeves (CON, <4 mmHg).
Running time, heart rate and muscle oxygenation of the medial gastrocnemius
muscle (measured using portable near-infrared spectroscopy) were monitored
continuously. Muscle functional capabilities (power, stiffness) were determined
using 20 s of maximal hopping before and after both sessions. Running
biomechanics (kinematics, vertical and leg stiffness) were determined at 12 km.h
1 at the beginning, during, and at the end of both sessions. Exercise-induced
Achilles tendon pain and delayed onset calf muscles soreness (DOMS) were assessed
using visual analog scales. Results: Muscle oxygenation increased significantly
in CS compared to CON at baseline and immediately after exercise (p < 0.05),
without any difference in deoxygenation kinetics during the run, and without any
significant change in run times. Wearing CS was associated with (i) higher aerial
time and leg stiffness in running at constant rate, (ii) with lower ground
contact time, higher leg stiffness, and higher vertical stiffness in all-out
running, and (iii) with lower ground contact time in hopping. Significant DOMS
were induced in both CS and CON (>6 on a 10-cm scale) with no difference between
conditions. However, Achilles tendon pain was significantly lower after the trial
in CS than CON (p < 0.05). Discussion: Calf compression did not modify muscle
oxygenation during ~2 h 30 of trail running but significantly changed running
biomechanics and lower limb muscle functional capabilities toward a more dynamic
behavior compared to control session. However, wearing compression sleeves did
not affect performance and exercise-induced DOMS, while it minimized Achilles
tendon pain immediately after running.
PMID- 28496412
TI - Nitric Oxide Synthase Activity Correlates with OGG1 in Ozone-Induced Lung Injury
Animal Models.
AB - Background: NO is an important cellular signaling molecule which is derived from
L-arginine by nitric oxide synthase (NOS) and the effects of NOS signaling in
lung injury is conflicting. The present study was designed to observe the effect
of NOS and Arginase signaling in the occurrence and development of lung injury
and its mechanism. Methods: An ozone-stressed lung injury animal model was
established by exposure to 2.0 ppm O3 for 30 min every day for consecutive 12 day
with or without the administration of NO precursor L-arginine or non-selective
NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME). Then, the lung
histopathology, the releases of inflammatory mediators and the production of ROS
were assayed by immunohistochemistry, ELISA and flow cytometry respectively. The
activities and expression of NOS and Arginase were assayed by biochemical methods
and western blot. Correspondingly, the release of 8-oxoguanine glycosylase 1(8
OxoG) and 8-oxoguanine glycosylase 1 (OGG1) were assayed by ELISA and western
blot. The correlation between NOS/Arginase signaling with 8-OxoG/ OGG1 was also
analyzed by Pearson correlation coefficients and immunofluorescence in NOS
deficient bronchial epithelial cells. Results: In ozone-induced rat lung injury
models, lung inflammation as well as lung architecture was disrupted in a time
dependent manner. Ozone treatment with L-arginine showed a substantial
attenuation of adverse lung histopathological changes and treatment with L-NAME
promoted the inflammation and remodeling. Importantly, the expression of NOS was
promoted by L-arginine and inhibited by L-NAME and the expression of Arginase was
promoted by L-NAME treatment. Further, we observed significantly higher levels of
8-OxoG and lower levels of OGG1 in ozone group which was reversed by L-arginine
and promoted by L-NAME. The expression of NOS is closely related with 8-OxoG
/OCG1. Conclusion: These findings give further evidence that the NOS signaling is
related with base excise repair.
PMID- 28496414
TI - The Systematic Bias of Ingestible Core Temperature Sensors Requires a Correction
by Linear Regression.
AB - An accurate measure of core body temperature is critical for monitoring
individuals, groups and teams undertaking physical activity in situations of high
heat stress or prolonged cold exposure. This study examined the range in
systematic bias of ingestible temperature sensors compared to a certified and
traceable reference thermometer. A total of 119 ingestible temperature sensors
were immersed in a circulated water bath at five water temperatures (TEMP A:
35.12 +/- 0.60 degrees C, TEMP B: 37.33 +/- 0.56 degrees C, TEMP C: 39.48 +/-
0.73 degrees C, TEMP D: 41.58 +/- 0.97 degrees C, and TEMP E: 43.47 +/- 1.07
degrees C) along with a certified traceable reference thermometer. Thirteen
sensors (10.9%) demonstrated a systematic bias > +/-0.1 degrees C, of which 4
(3.3%) were > +/- 0.5 degrees C. Limits of agreement (95%) indicated that
systematic bias would likely fall in the range of -0.14 to 0.26 degrees C,
highlighting that it is possible for temperatures measured between sensors to
differ by more than 0.4 degrees C. The proportion of sensors with systematic bias
> +/-0.1 degrees C (10.9%) confirms that ingestible temperature sensors require
correction to ensure their accuracy. An individualized linear correction achieved
a mean systematic bias of 0.00 degrees C, and limits of agreement (95%) to 0.00
0.00 degrees C, with 100% of sensors achieving +/-0.1 degrees C accuracy.
Alternatively, a generalized linear function (Corrected Temperature ( degrees C)
= 1.00375 * Sensor Temperature ( degrees C) - 0.205549), produced as the average
slope and intercept of a sub-set of 51 sensors and excluding sensors with
accuracy outside +/-0.5 degrees C, reduced the systematic bias to < +/-0.1
degrees C in 98.4% of the remaining sensors (n = 64). In conclusion, these data
show that using an uncalibrated ingestible temperature sensor may provide
inaccurate data that still appears to be statistically, physiologically, and
clinically meaningful. Correction of sensor temperature to a reference
thermometer by linear function eliminates this systematic bias (individualized
functions) or ensures systematic bias is within +/-0.1 degrees C in 98% of the
sensors (generalized function).
PMID- 28496413
TI - Cholera Toxin Induces Sustained Hyperexcitability in Myenteric, but Not
Submucosal, AH Neurons in Guinea Pig Jejunum.
AB - Background and Aims: Cholera toxin (CT)-induced hypersecretion requires
activation of secretomotor pathways in the enteric nervous system (ENS). AH
neurons, which have been identified as a population of intrinsic sensory neurons
(ISNs), are a source of excitatory input to the secretomotor pathways. We
therefore examined effects of CT in the intestinal lumen on myenteric and
submucosal AH neurons. Methods: Isolated segments of guinea pig jejunum were
incubated for 90 min with saline plus CT (12.5 MUg/ml) or CT + neurotransmitter
antagonist, or CT + tetrodotoxin (TTX) in their lumen. After washing CT away,
submucosal or myenteric plexus preparations were dissected keeping
circumferentially adjacent mucosa intact. Submucosal AH neurons were impaled
adjacent to intact mucosa and myenteric AH neurons were impaled adjacent to, more
than 5 mm from, and in the absence of intact mucosa. Neuronal excitability was
monitored by injecting 500 ms current pulses through the recording electrode.
Results: After CT pre-treatment, excitability of myenteric AH neurons adjacent to
intact mucosa (n = 29) was greater than that of control neurons (n = 24), but
submucosal AH neurons (n = 33, control n = 27) were unaffected. CT also induced
excitability increases in myenteric AH neurons impaled distant from the mucosa (n
= 6) or in its absence (n = 5). Coincubation with tetrodotoxin or SR142801 (NK3
receptor antagonist), but not SR140333 (NK1 antagonist) or granisetron (5-HT3
receptor antagonist) prevented the increased excitability induced by CT.
Increased excitability was associated with a reduction in the characteristic AHP
and an increase in the ADP of these neurons, but not a change in the
hyperpolarization-activated inward current, Ih . Conclusions: CT increases
excitability of myenteric, but not submucosal, AH neurons. This is neurally
mediated and depends on NK3, but not 5-HT3 receptors. Therefore, CT may act to
amplify the secretomotor response to CT via an increase in the activity of the
afferent limb of the enteric reflex circuitry.
PMID- 28496415
TI - Inflammatory Effects of Menthol vs. Non-menthol Cigarette Smoke Extract on Human
Lung Epithelial Cells: A Double-Hit on TRPM8 by Reactive Oxygen Species and
Menthol.
AB - Clinical studies suggest that smokers with chronic obstructive pulmonary disease
who use menthol cigarettes may display more severe lung inflammation than those
who smoke non-menthol cigarette. However, the mechanisms for this difference
remain unclear. Menthol is a ligand of transient receptor potential melastatin-8
(TRPM8), a Ca2+-permeant channel sensitive to reactive oxygen species (ROS). We
previously reported that exposure of human bronchial epithelial cells (HBECs) to
non-menthol cigarette smoke extract (Non-M-CSE) triggers a cascade of
inflammatory signaling leading to IL-8 induction. In this study, we used this in
vitro model to compare the inflammatory effects of menthol cigarette smoke
extract (M-CSE) and Non-M-CSE and delineate the mechanisms underlying the
differences in their impacts. Compared with Non-M-CSE, M-CSE initially increased
a similar level of extracellular ROS, suggesting the equivalent oxidant potency.
However, M-CSE subsequently produced more remarkable elevations in intracellular
Ca2+, activation of the mitogen-activated protein kinases (MAPKs)/nuclear factor
kappaB (NF-kappaB) signaling, and IL-8 induction. The extracellular ROS responses
to both CSE types were totally inhibited by N-acetyl-cysteine (NAC; a ROS
scavenger). The intracellular Ca2+ responses to both CSE types were also totally
prevented by NAC, AMTB (a TRPM8 antagonist), or EGTA (an extracellular Ca2+
chelator). The activation of the MAPK/NF-kappaB signaling and induction of IL-8
to both CSE types were suppressed to similar levels by NAC, AMTB, or EGTA. These
results suggest that, in addition to ROS generated by both CSE types, the menthol
in M-CSE may act as another stimulus to further activate TRPM8 and induce the
observed responses. We also found that menthol combined with Non-M-CSE induced
greater responses of intracellular Ca2+ and IL-8 compared with Non-M-CSE alone.
Moreover, we confirmed the essential role of TRPM8 in these responses to Non-M
CSE or M-CSE and the difference in these responses between the both CSE types
using HBECs with TRPM8 knockdown and TRPM8 knockout, and using HEK293 cells
transfected with hTRPM8. Thus, compared with exposure to Non-M-CSE, exposure to M
CSE induced greater TRPM8-mediated inflammatory responses in HBECs. These
augmented effects may be due to a double-hit on lung epithelial TRPM8 by ROS
generated from CSE and the menthol in M-CSE.
PMID- 28496416
TI - Lysophosphatidic Acid Is Associated with Atherosclerotic Plaque Instability by
Regulating NF-kappaB Dependent Matrix Metalloproteinase-9 Expression via LPA2 in
Macrophages.
AB - Lysophosphatidic acid (LPA), one of the simplest phospholipid signaling
molecules, participates in formation and disruption of atherosclerotic plaque.
Matrix metalloproteinases (MMPs) contribute to atherosclerotic plaque rupture by
involving in extracellular matrix (ECM) degradation and then thinning fibrous
cap. Our previous study demonstrated that macrophage-derived MMP-9 was associated
with coronary plaque instability, but the relationship between LPA and MMP-9
remains unclear. The present work therefore aimed at elucidating association
between LPA and MMP-9 and the regulation mechanism of LPA on MMP-9 in
macrophages. We found that plasma LPA and MMP-9 levels were correlated positively
(r = 0.31, P < 0.05) and both elevated significantly in patients with acute
myocardial infarct (AMI). Consistent with peripheral blood levels, histochemical
staining indicated that autotaxin (ATX), LPA-producing ectoenzyme, and MMP-9 were
expressed frequently in the necrotic core and fibrous cap of human unstable
plaques, which might increase the instability of plaque. Experiments in vitro
were done with THP-1-derived macrophages and showed that LPA enhanced the
expression, secretion and activity of MMP-9 in a time- and dose-dependent manner.
Induction of LPA on pro-MMP-9 and active-MMP-9 was confirmed in human peripheral
blood monocyte-derived macrophages. PDTC, NF-kappaB inhibitor, but not inhibitor
of AP-1 and PPARgamma, effectively prevented LPA-induced MMP-9 expression and NF
kappaB p65 siRNA decreased MMP-9 transcription, confirming that LPA might induce
MMP-9 elevation by activating NF-kappaB pathway. In addition, knockdown of LPA2
attenuated LPA-induced MMP-9 expression and nucleus p65 levels. These findings
revealed that LPA upregulated the expression of MMP-9 through activating NF
kappaB pathway in the LPA2 dependent manner, hence blocking LPA receptors
signaling may provide therapeutic strategy to target plaque destabilization.
PMID- 28496417
TI - Corrigendum: Characterization of Reproductive Dormancy in Male Drosophila
melanogaster.
AB - [This corrects the article on p. 572 in vol. 7, PMID: 27932997.].
PMID- 28496419
TI - Comparison and Outcome Analysis of Patients with Takotsubo Cardiomyopathy
Triggered by Emotional Stress or Physical Stress.
AB - Background: Previous studies revealed that takotsubo cardiomyopathy (TTC) is
triggered by physical and emotional stresses. This study was performed to
determine the short- and long-term prognostic impact of emotional- and physical
stress associated with TTC. Methods and results: Our institutional database
constituted a collective of 84 patients diagnosed with TTC between 2003 and 2015.
The patients were divided into two groups as per the presence of emotional stress
(n = 24, 21%) or physical stress (n = 60, 52.6%). The endpoint was a composite of
in-hospital events (thromboembolic events and life-threatening arrhythmias),
myocardial infarction, all-cause of mortality, re-hospitalization due to heart
failure, stroke, and recurrence of TTC. A Kaplan-Meier analysis indicated a
significantly lower event-free survival rate over a mean follow-up of 5 years in
the emotional group than the physical stress group (log-rank, p < 0.01).
Multivariate Cox regression analysis revealed only emotional stress (HR 0.4, 95%
CI: 0.2-0.9, p < 0.05) as a negative independent predictor of the primary
endpoint. Conclusion: Rates of in-hospital events and short- as well as long-term
events were significantly lower in TTC patients suffering from emotional stress
as compared to patients with physical stress.
PMID- 28496420
TI - Impaired Maintenance of Interpersonal Synchronization in Musical Improvisations
of Patients with Borderline Personality Disorder.
AB - Borderline personality disorder (BPD) is a serious and complex mental disorder
with a lifetime prevalence of 5.9%, characterized by pervasive difficulties with
emotion regulation, impulse control, and instability in interpersonal
relationships and self-image. Impairments in interpersonal functioning have
always been a prominent characteristic of BPD, indicating a need for research to
identify the specific interpersonal processes that are problematic for diagnosed
individuals. Previous research has concentrated on self-report questionnaires,
unidirectional tests, and experimental paradigms wherein the exchange of social
signals between individuals was not the focus. We propose joint musical
improvisation as an alternative method to investigate interpersonal processes.
Using a novel, carefully planned, ABA' accompaniment paradigm, and taking into
account the possible influences of mood, psychotropic medication, general
attachment, and musical sophistication, we recorded piano improvisations of 16
BPD patients and 12 matched healthy controls. We hypothesized that the insecure
attachment system associated with BPD would be activated in the joint
improvisation and manifest in measures of timing behavior. Results indicated that
a logistic regression model, built on differences in timing deviations, predicted
diagnosis with 82% success. More specifically, over the course of the
improvisation B section (freer improvisation), controls' timing deviations
decreased (temporal synchrony became more precise) whereas that of the patients
with BPD did not, confirming our hypothesis. These findings are in accordance
with previous research, where BPD is characterized by difficulties in attachment
relationships such as maintaining strong attachment with others, but it is novel
to find empirical evidence of such issues in joint musical improvisation. We
suggest further longitudinal research within the field of music therapy, to study
how recovery of these timing habits are related to attachment experiences and
interpersonal functioning in general.
PMID- 28496418
TI - Toward the Identification of a Specific Psychopathology of Substance Use
Disorders.
AB - Addiction is a mental illness in which psychiatric conditions imply a prominent
burden. Psychopathological symptoms in substance use disorder (SUD) patients are
usually viewed as being assignable to the sphere of a personality trait or of
comorbidity, leaving doubts about the presence of a specific psychopathology that
could only be related to the toxicomanic process. Our research group at the
University of Pisa has shed light on the possible definition of a specific
psychopathological dimension in SUDs. In heroin use disorder patients, performing
an exploratory principal component factor analysis (PCA) on all the 90 items
included in the SCL-90 questionnaire led to a five-factor solution. The first
factor accounted for a depressive "worthlessness and being trapped" dimension;
the second factor picked out a "somatic symptoms" dimension; the third identified
a "sensitivity-psychoticism" dimension; the fourth a "panic-anxiety" dimension;
and the fifth a "violence-suicide" dimension. These same results were replicated
by applying the PCA to another Italian sample of 1,195 heroin addicts entering a
Therapeutic Community Treatment. Further analyses confirmed the clusters of
symptoms, independently of demographic and clinical characteristics, active
heroin use, lifetime psychiatric problems, kind of treatment received, and,
especially, other substances used by the patient such as alcohol or cocaine.
Moreover, these clusters were able to discriminate patients affected by addiction
from those affected by psychiatric diseases such as major depressive disorder.
Our studies seem to suggest the trait-dependent, rather than the state-dependent,
nature of the introduced psychopathology dimensions of SUDs.
PMID- 28496421
TI - The Positivity Bias Phenomenon in Face Perception Given Different Information on
Ability.
AB - The negativity bias has been shown in many fields, including in face processing.
We assume that this bias stems from the potential threat inlayed in the stimuli
(e.g., negative moral behaviors) in previous studies. In the present study, we
conducted one behavioral and one event-related potentials (ERPs) experiments to
test whether the positivity bias rather than negativity bias will arise when
participants process information whose negative aspect involves no threat, i.e.,
the ability information. In both experiments, participants first completed a
valence rating (negative-to-positive) of neutral facial expressions. Further, in
the learning period, participants associated the neutral faces with high-ability,
low-ability, or control sentences. Finally, participants rated these facial
expressions again. Results of the behavioral experiment showed that compared with
pre-learning, the expressions of the faces associated with high ability sentences
were classified as more positive in the post-learning expression rating task, and
the faces associated with low ability sentences were evaluated as more negative.
Meanwhile, the change in the high-ability group was greater than that of the low
ability group. The ERP data showed that the faces associated with high-ability
sentences elicited a larger early posterior negativity, an ERP component
considered to reflect early sensory processing of the emotional stimuli, than the
faces associated with control sentences. However, no such effect was found in
faces associated with low-ability sentences. To conclude, high ability sentences
exerted stronger influence on expression perception than did low ability ones.
Thus, we found a positivity bias in this ability-related facial perceptual task.
Our findings demonstrate an effect of valenced ability information on face
perception, thereby adding to the evidence on the opinion that person-related
knowledge can influence face processing. What's more, the positivity bias in non
threatening surroundings increases scope for studies on processing bias.
PMID- 28496422
TI - Systematic Observation of an Expert Driver's Gaze Strategy-An On-Road Case Study.
AB - In this paper we present and qualitatively analyze an expert driver's gaze
behavior in natural driving on a real road, with no specific experimental task or
instruction. Previous eye tracking research on naturalistic tasks has revealed
recurring patterns of gaze behavior that are surprisingly regular and repeatable.
Lappi (2016) identified in the literature seven "qualitative laws of gaze
behavior in the wild": recurring patterns that tend to go together, the more so
the more naturalistic the setting, all of them expected in extended sequences of
fully naturalistic behavior. However, no study to date has observed all in a
single experiment. Here, we wanted to do just that: present observations
supporting all the "laws" in a single behavioral sequence by a single subject. We
discuss the laws in terms of unresolved issues in driver modeling and open
challenges for experimental and theoretical development.
PMID- 28496423
TI - The Inhibitory Mechanism in Learning Ambiguous Words in a Second Language.
AB - Ambiguous words are hard to learn, yet little is known about what causes this
difficulty. The current study aimed to investigate the relationship between the
representations of new and prior meanings of ambiguous words in second language
(L2) learning, and to explore the function of inhibitory control on L2 ambiguous
word learning at the initial stage of learning. During a 4-day learning phase,
Chinese-English bilinguals learned 30 novel English words for 30 min per day
using bilingual flashcards. Half of the words to be learned were unambiguous (had
one meaning) and half were ambiguous (had two semantically unrelated meanings
learned in sequence). Inhibitory control was introduced as a subject variable
measured by a Stroop task. The semantic representations established for the
studied items were probed using a cross-language semantic relatedness judgment
task, in which the learned English words served as the prime, and the targets
were either semantically related or unrelated to the prime. Results showed that
response latencies for the second meaning of ambiguous words were slower than for
the first meaning and for unambiguous words, and that performance on only the
second meaning of ambiguous words was predicted by inhibitory control ability.
These results suggest that, at the initial stage of L2 ambiguous word learning,
the representation of the second meaning is weak, probably interfered with by the
representation of the prior learned meaning. Moreover, inhibitory control may
modulate learning of the new meanings, such that individuals with better
inhibitory control may more effectively suppress interference from the first
meaning, and thus learn the new meaning more quickly.
PMID- 28496424
TI - The German Version of the Strengths Use Scale: The Relation of Using Individual
Strengths and Well-being.
AB - Theoretical perspectives in positive psychology have considered the possession
and use of strengths equally but in applied research more studies focused on
having them, probably due to the absence of psychometrically adequate scales.
Therefore, the aim of this study was to assess the psychometric characteristics
of the German language version of the Strengths Use Scale (SUS) and to explore
relationships between strengths use and several indicator measures of well-being:
the presence of positive and the absence of negative affect, self-esteem as
identity aspect, vitality as self-regulatory resource, and stress for capturing
the evaluation of difficulties and obstacles impinging on well-being. The
original English version of the SUS was translated following recommended
independent forward-backward translation techniques. Exploratory and confirmatory
factor analyses were conducted, including a German-speaking convenience sample of
university students (N = 374). Additionally, the relations of strengths use and
well-being indicators were analyzed. Factorial validity revealed a single-factor
structure of the German version of the SUS, explaining 58.4% variance (factor
loadings: 0.58 to 0.86), approving the scale's design and showing high internal
consistency (Cronbach's alpha 0.95). The hypothesized positive relationships of
strengths use with positive affect, self-esteem, and vitality were confirmed as
well as the negative relationships with negative affect and stress. The German
version of the SUS is psychometrically sound and data indicate that individual
strengths use and well-being related measures interact. The instrument can be
recommended for future research questions such as if and how the promotion of
applying individual strengths during education enhances levels of well-being, or
how the implementation of strengths use in job-design guidelines or working
conditions can result in higher levels of well-being or healthiness.
PMID- 28496425
TI - Verbalizations Affect Visuomotor Control in Hitting Objects to Distant Targets.
AB - There is a long-standing proposal for the existence of two neuroanatomically and
functionally separate visual systems; one supported by the dorsal pathway to
control action and the second supported by the ventral pathway to handle explicit
perceptual judgments. The dorsal pathway requires fast access to egocentric
information, while the ventral pathway primarily requires allocentric
information. Despite the evidence for functionally distinct systems, researchers
have posited important interactions. This paper examines evidence to what degree
the interaction becomes more important when target-identity, the perception of
which is supported by the ventral stream, is verbalized during the execution of a
target-directed far-aiming movement. In the experiment reported here participants
hit balls toward distant targets while concurrently making explicit perceptual
judgments of target properties. The endpoint of a shaft served as the target,
with conditions including illusory arrow fins at the endpoint. Participants
verbalized the location of the target by comparing it to a reference line and
calling out "closer" or "further" while propelling the ball to the target. The
impact velocity at ball contact was compared for hits toward three shafts of
lengths, 94, 100, and 106 cm, with and without verbalizations and delays. It was
observed that the meaning of the expressed words modulated movement execution
when the verbalizations were consistent with the action characteristics. This
effect of semantic content was evident regardless of target visibility during
movement execution, demonstrating it was not restricted to movements that rely on
visual memory. In addition to a direct effect of semantic content we anticipated
an indirect effect of verbalization to result in action shifting toward the use
of context-dependent allocentric information. This would result in an illusion
bias on the impact velocity when the target is embedded in a Muller-Lyer
configuration. We observed an ubiquitous effect of illusory context on movement
execution, and not only when verbalizations were made. We suggest that the
current experimental design with a far-aiming task where most conditions required
reporting or retaining spatial characteristics of targets for action over time
may have elicited a strong reliance on allocentric information to guide action.
PMID- 28496426
TI - Chronic Pain as a Hypothetical Construct: A Practical and Philosophical
Consideration.
AB - Pain has been defined by the International Association for the Study of Pain
(IASP) as "an unpleasant sensory and emotional experience associated with actual
or potential tissue damage, or described in terms of such damage." Chronic pain
is usually described as pain that has persisted for 3-6 months and/or beyond the
expected time of healing. The numerical pain rating (NPR) is the customary metric
and often considered as a proxy for the subjective experience of chronic pain.
This definition of pain (chronic) has been of significant heuristic value.
However, the definition and the models it has spawned tend to encourage the
interpretation of pain as a measurable entity and implies that the patient's
experience of pain can be fully comprehended by someone other than the person in
pain. Several major models of pain have been scrutinized and found to propagate
the notion of pain as a 'thing' and fall prey to biomedical reductionism and
Cartesian (mind-body) dualism. Furthermore, the NPR does not appear to capture
the complexity of chronic pain and correlates poorly with other clinically
meaningful outcomes. It, and other aspects of the current notion of chronic pain,
appear to be an extension of our reliance on the philosophical principles of
reductionism and materialism. These and other shortcomings identified in the IASP
definition have resulted in an increased interest in a reexamination and possible
updating of our view of pain (chronic) and its definition. The present paper
describes an alternative view of pain, in particular chronic pain. It argues that
chronic pain should be understood as a separate phenomenon from, rather than an
extension of, acute pain and interpreted as a hypothetical construct (HC). HCs
are contrasted to intervening variables (IV) and the use of HCs in science is
illustrated. The acceptance of the principles of nonlinearity and emergence are
seen as important characteristics. The practical implications and barriers of
this philosophical shift for assessment, treatment, and education are explored.
The patient's narrative is presented as a potential source of important
phenomenological data relating to their 'experience' of pain. It is further
proposed that educational and academic endeavors incorporate a discussion of the
process of chronification and the role of complexity theory.
PMID- 28496427
TI - The Relationship between SES and Reading Comprehension in Chinese: A Mediation
Model.
AB - An increasing body of research provides evidence that socioeconomic status (SES)
was significantly related to children's reading development; however, the
psychological mechanism underlying the association between them remained an open
question. The present study is designed to test the hypothesized three-path
effect of vocabulary knowledge and morphological awareness as mediators between
SES and sentence reading comprehension in Chinese first-graders. Results of
mediation model showed that SES exerted its effect on sentence reading
comprehension through the indirect path via the simple mediating effect of
morphological awareness and the three-path mediating effect of vocabulary
knowledge and morphological awareness. The findings highlight a previously
unidentified mechanism of the relationship between SES and reading comprehension
in Chinese young children.
PMID- 28496428
TI - Effect of Cyclosporine on Lesion Growth and Infarct Size within the White and
Gray Matter.
AB - BACKGROUND: In a recent trial, cyclosporine A (CsA) failed to reduce infarct size
in acute stroke patients treated with intravenous thrombolysis. White matter (WM)
and gray matter (GM) may have distinct vulnerability to ischemia and response to
therapy. Using final infarct size and lesion growth as endpoints, our objectives
were to (1) investigate any tissue-specific effect of CsA and (2) compare WM and
GM response to thrombolysis. MATERIALS AND METHODS: We analyzed 84 patients from
the randomized and placebo-controlled CsA-Stroke trial, who underwent MRI both on
admission and at 1 month. Lesion growth was defined voxel-wise as infarcted
tissue at 1 month with no visible lesion on baseline diffusion-weighted imaging.
After automatic segmentation of GM/WM, final infarct size and lesion growth were
compared within the GM and WM. RESULTS: Occlusion level was distal (>M1) in 51%
of cases. No significant difference in GM/WM proportions was observed within
final infarcts between treatment groups (P = 0.21). Infarct size within the GM or
WM was similar between the CsA and control groups [GM: 9.2 (2.4; 22.8) with CsA
vs 8.9 (3.7; 28.4) mL with placebo, P = 0.74; WM: 9.9 (4.7; 25.4) with CsA vs
14.1 (5.6; 34.1) mL with placebo, P = 0.26]. There was no significant effect of
CsA on lesion growth in either the GM or WM. Pooling all patients, a trend for
increased relative lesion growth in WM compared to GM was observed [49.0% (14.7;
185.7) vs 43.1% (15.4; 117.1), respectively; P = 0.12]. CONCLUSION: No
differential effect of CsA was observed between WM and GM. Pooling all patients,
a trend toward greater lesion growth in WM was observed.
PMID- 28496429
TI - Molecular Mechanisms Regulating Temperature Compensation of the Circadian Clock.
AB - An approximately 24-h biological timekeeping mechanism called the circadian clock
is present in virtually all light-sensitive organisms from cyanobacteria to
humans. The clock system regulates our sleep-wake cycle, feeding-fasting,
hormonal secretion, body temperature, and many other physiological functions.
Signals from the master circadian oscillator entrain peripheral clocks using a
variety of neural and hormonal signals. Even centrally controlled internal
temperature fluctuations can entrain the peripheral circadian clocks. But, unlike
other chemical reactions, the output of the clock system remains nearly constant
with fluctuations in ambient temperature, a phenomenon known as temperature
compensation. In this brief review, we focus on recent advances in our
understanding of the posttranslational modifications, especially a phosphoswitch
mechanism controlling the stability of PER2 and its implications for the
regulation of temperature compensation.
PMID- 28496430
TI - Cholinergic Nociceptive Mechanisms in Rat Meninges and Trigeminal Ganglia:
Potential Implications for Migraine Pain.
AB - BACKGROUND: Parasympathetic innervation of meninges and ability of carbachol,
acetylcholine (ACh) receptor (AChR) agonist, to induce headaches suggests
contribution of cholinergic mechanisms to primary headaches. However,
neurochemical mechanisms of cholinergic regulation of peripheral nociception in
meninges, origin place for headache, are almost unknown. METHODS: Using
electrophysiology, calcium imaging, immunohistochemistry, and staining of
meningeal mast cells, we studied effects of cholinergic agents on peripheral
nociception in rat hemiskulls and isolated trigeminal neurons. RESULTS: Both ACh
and carbachol significantly increased nociceptive firing in peripheral terminals
of meningeal trigeminal nerves recorded by local suction electrode. Strong
nociceptive firing was also induced by nicotine, implying essential role of
nicotinic AChRs in control of excitability of trigeminal nerve endings.
Nociceptive firing induced by carbachol was reduced by muscarinic antagonist
atropine, whereas the action of nicotine was prevented by the nicotinic blocker d
tubocurarine but was insensitive to the TRPA1 antagonist HC-300033. Carbachol but
not nicotine induced massive degranulation of meningeal mast cells known to
release multiple pro-nociceptive mediators. Enzymes terminating ACh action,
acetylcholinesterase (AChE) and butyrylcholinesterase, were revealed in
perivascular meningeal nerves. The inhibitor of AChE neostigmine did not change
the firing per se but induced nociceptive activity, sensitive to d-tubocurarine,
after pretreatment of meninges with the migraine mediator CGRP. This observation
suggested the pro-nociceptive action of endogenous ACh in meninges. Both nicotine
and carbachol induced intracellular Ca2+ transients in trigeminal neurons
partially overlapping with expression of capsaicin-sensitive TRPV1 receptors.
CONCLUSION: Trigeminal nerve terminals in meninges, as well as dural mast cells
and trigeminal ganglion neurons express a repertoire of pro-nociceptive nicotinic
and muscarinic AChRs, which could be activated by the ACh released from
parasympathetic nerves. These receptors represent a potential target for novel
therapeutic interventions in trigeminal pain and probably in migraine.
PMID- 28496431
TI - Sex Differences in Outcomes among Stroke Survivors with Non-Valvular Atrial
Fibrillation in China.
AB - Atrial fibrillation (AF) significantly increases the risk of stroke and disease
burden and is an established predictor of poor outcomes after stroke. However,
data regarding sex differences in long-term outcomes following stroke in patients
with AF are scarce. We thus aimed to assess these differences. We recruited 951
consecutive patients with acute ischemic stroke and non-valvular atrial
fibrillation (NVAF) treated at three hospitals in Tianjin, China, from January
2006 to September 2014. Information regarding stroke subtype, severity, risk
factors, and outcomes (mortality, dependency, and recurrence) at 3, 12, and 36
months after stroke was recorded. The prevalence of NVAF was 8.4% overall, with a
higher frequency in women than in men (11.3 vs. 6.9%, P < 0.001). Among patients
with NVAF, women were older than men. Women were more likely than men to have
severe stroke (38.8 vs. 29.5%, P < 0.001), high levels of total cholesterol and
high- and low-density lipoprotein cholesterol (all P < 0.001), hypertension (69.1
vs. 61.2%, P = 0.012), dyslipidemia (29.8 vs. 20.7%, P = 0.001), and obesity
(18.5 vs. 11.6%, P = 0.003); they were less likely than men to be current smokers
(12.2 vs. 33.6%, P < 0.001) and to consume alcohol (0.9 vs. 13.9%, P < 0.001).
There were greater risks of dependency and recurrence at 36 months after stroke
in women than in men [odds ratios (95% confidence intervals), 1.64 (1.02-2.64)
for dependency, P = 0.043; and 2.03 (1.28-3.20) for recurrence, P = 0.002] after
adjustment for stroke subtype, severity, and risk factors. These findings suggest
that it is crucial to emphasize the need for individualized stroke prevention
education and promotion of healthy lifestyles in order to improve NVAF-related
stroke outcomes and reduce disease burden in women.
PMID- 28496432
TI - Vestibular Loss in Older Adults Is Associated with Impaired Spatial Navigation:
Data from the Triangle Completion Task.
AB - BACKGROUND: Vestibular inputs have been shown to play a critical role in spatial
navigation. In this study, we sought to evaluate whether vestibular loss due to
aging contributes to impaired spatial navigation as measured by the triangle
completion task (TCT). MATERIALS AND METHODS: We recruited three types of
participants: young controls <55 years of age, older controls >=55 years of age,
and older patients from a Neurotology Clinic with evidence of vestibular
physiologic impairment but who did not have any known vestibular disorder. We
performed the cervical vestibular-evoked myogenic potential to evaluate saccular
function and video head impulse testing to quantify horizontal semicircular canal
vestibulo-ocular reflex gain. To assess spatial navigation ability, we
administered the TCT, in which participants were conveyed along two segments of a
pre-drawn triangular path and instructed to complete the final segment
independently. We measured the angle (degrees) and distance (centimeters) of
deviation from the correct trajectory. We evaluated the influence of vestibular
inputs on TCT performance. RESULTS: Forty-eight adults participated in the study
(mean age: 62.0 years; 52.1% females), including 9 young controls, 15 older
controls, and 24 clinic patients. Clinic patients had the greatest distance of
deviation (67.7 cm), followed by older controls (45.4 cm), then young controls
(27.8 cm; p < 0.01). Similarly, clinic patients had greater rotational angles
(22.1 degrees ) compared to older (13.3 degrees ) and younger controls (12.4
degrees ; p < 0.01). Following multivariate linear regression adjusting for
demographic variables, loss of otolith function was associated with an 18.2 cm
increase in distance of deviation (95% CI: 15.2-47.4) and a 9.2 degrees increase
in rotational angle (95% CI: 3.0-15.5). Abnormal semicircular canal function was
associated with a 26.0 cm increase in distance of deviation (95% CI: 0.2-51.8)
and a 10.8 degrees increase in rotational angle (95% CI: 3.0-15.5). Participants
with both otolith and canal abnormalities had a larger distance error (beta =
25.3, 95% CI: 6.2-44.4) and angle of deviation (beta = 18.1, 95% CI: 10.1-26.2)
than with either condition alone. CONCLUSION: Vestibular loss in older adults was
associated with poorer performance on a dynamic spatial navigation task relative
to old and young controls.
PMID- 28496433
TI - Interplay between Mutations and Efflux in Drug Resistant Clinical Isolates of
Mycobacterium tuberculosis.
AB - Numerous studies show efflux as a universal bacterial mechanism contributing to
antibiotic resistance and also that the activity of the antibiotics subject to
efflux can be enhanced by the combined use of efflux inhibitors. Nevertheless,
the contribution of efflux to the overall drug resistance levels of clinical
isolates of Mycobacterium tuberculosis is poorly understood and still is ignored
by many. Here, we evaluated the contribution of drug efflux plus target-gene
mutations to the drug resistance levels in clinical isolates of M. tuberculosis.
A panel of 17 M. tuberculosis clinical strains were characterized for drug
resistance associated mutations and antibiotic profiles in the presence and
absence of efflux inhibitors. The correlation between the effect of the efflux
inhibitors and the resistance levels was assessed by quantitative drug
susceptibility testing. The bacterial growth/survival vs. growth inhibition was
analyzed through the comparison between the time of growth in the presence and
absence of an inhibitor. For the same mutation conferring antibiotic resistance,
different MICs were observed and the different resistance levels found could be
reduced by efflux inhibitors. Although susceptibility was not restored, the
results demonstrate the existence of a broad-spectrum synergistic interaction
between antibiotics and efflux inhibitors. The existence of efflux activity was
confirmed by real-time fluorometry. Moreover, the efflux pump genes mmr, mmpL7,
Rv1258c, p55, and efpA were shown to be overexpressed in the presence of
antibiotics, demonstrating the contribution of these efflux pumps to the overall
resistance phenotype of the M. tuberculosis clinical isolates studied,
independently of the genotype of the strains. These results showed that the drug
resistance levels of multi- and extensively-drug resistant M. tuberculosis
clinical strains are a combination between drug efflux and the presence of target
gene mutations, a reality that is often disregarded by the tuberculosis
specialists in favor of the almost undisputed importance of antibiotic target
gene mutations for the resistance in M. tuberculosis.
PMID- 28496435
TI - Serum Metabolomic Profiling of Piglets Infected with Virulent Classical Swine
Fever Virus.
AB - Classical swine fever (CSF) is a highly contagious swine infectious disease and
causes significant economic losses for the pig industry worldwide. The objective
of this study was to determine whether small molecule metabolites contribute to
the pathogenesis of CSF. Birefly, serum metabolomics of CSFV Shimen strain
infected piglets were analyzed by ultraperformance liquid
chromatography/electrospray ionization time-of-flight mass spectrometry (UPLC/ESI
Q-TOF/MS) in combination with multivariate statistical analysis. In CSFV-infected
piglets at days 3 and 7 post-infection changes were found in metabolites
associated with several key metabolic pathways, including tryptophan catabolism
and the kynurenine pathway, phenylalanine metabolism, fatty acid and lipid
metabolism, the tricarboxylic acid and urea cycles, branched-chain amino acid
metabolism, and nucleotide metabolism. Several pathways involved in energy
metabolism including fatty acid biosynthesis and beta-oxidation, branched-chain
amino acid metabolism, and the tricarboxylic acid cycle were significantly
inhibited. Changes were also observed in several metabolites exclusively
associated with gut microbiota. The metabolomic profiles indicate that CSFV-host
gut microbiome interactions play a role in the development of CSF.
PMID- 28496436
TI - Myxococcus xanthus DK1622 Coordinates Expressions of the Duplicate groEL and
Single groES Genes for Synergistic Functions of GroELs and GroES.
AB - Chaperonin GroEL (Cpn60) requires cofactor GroES (Cpn10) for protein refolding in
bacteria that possess single groEL and groES genes in a bicistronic groESL
operon. Among 4,861 completely-sequenced prokaryotic genomes, 884 possess
duplicate groEL genes and 770 possess groEL genes with no neighboring groES. It
is unclear whether stand-alone groEL requires groES in order to function and, if
required, how duplicate groEL genes and unequal groES genes balance their
expressions. In Myxococcus xanthus DK1622, we determined that, while duplicate
groELs were alternatively deletable, the single groES that clusters with groEL1
was essential for cell survival. Either GroEL1 or GroEL2 required interactions
with GroES for in vitro and in vivo functions. Deletion of groEL1 or groEL2
resulted in decreased expressions of both groEL and groES; and ectopic
complementation of groEL recovered not only the groEL but also groES expressions.
The addition of an extra groES gene upstream groEL2 to form a bicistronic operon
had almost no influence on groES expression and the cell survival rate, whereas
over-expression of groES using a self-replicating plasmid simultaneously
increased the groEL expressions. The results indicated that M. xanthus DK1622
cells coordinate expressions of the duplicate groEL and single groES genes for
synergistic functions of GroELs and GroES. We proposed a potential regulation
mechanism for the expression coordination.
PMID- 28496434
TI - A Critical Assessment of the Microorganisms Proposed to be Important to Enhanced
Biological Phosphorus Removal in Full-Scale Wastewater Treatment Systems.
AB - Understanding the microbiology of phosphorus (P) removal is considered essential
to knowledge-based optimization of enhanced biological P removal (EBPR) systems.
Biological P removal is achieved in these systems by promoting the growth of
organisms collectively known as the polyphosphate accumulating organisms (PAOs).
Also considered important to EBPR are the glycogen accumulating organisms (GAOs),
which are theorized to compete with the PAOs for resources at the expense of P
removal efficiency. Numerous studies have sought to identify the PAOs and their
GAOs competitors, with several candidates proposed for each over the last few
decades. The current study collectively assessed the abundance and diversity of
all proposed PAOs and GAOs in 18 Danish full-scale wastewater treatment plants
with well-working biological nutrient removal over a period of 9 years using 16S
rRNA gene amplicon sequencing. The microbial community structure in all plants
was relatively stable over time. Evidence for the role of the proposed PAOs and
GAOs in EBPR varies and is critically assessed, in light of their calculated
amplicon abundances, to indicate which of these are important in full-scale
systems. Bacteria from the genus Tetrasphaera were the most abundant of the PAOs.
The "Candidatus Accumulibacter" PAOs were in much lower abundance and appear to
be biased by the amplicon-based method applied. The genera Dechloromonas,
Microlunatus, and Tessaracoccus were identified as abundant putative PAO that
require further research attention. Interestingly, the actinobacterial
Micropruina and sbr-gs28 phylotypes were among the most abundant of the putative
GAOs. Members of the genera Defluviicoccus, Propionivibrio, the family
Competibacteraceae, and the spb280 group were also relatively abundant in some
plants. Despite observed high abundances of GAOs (periodically exceeding 20% of
the amplicon reads), P removal performance was maintained, indicating that these
organisms were not outcompeting the PAOs in these EBPR systems. Phylogenetic
diversity within each of the PAOs and GAOs genera was observed, which is
consistent with reported metabolic diversity for these. Whether or not key traits
can be assigned to sub-genus level clades requires further investigation.
PMID- 28496437
TI - Bacillus anthracis Peptidoglycan Integrity Is Disrupted by the Chemokine CXCL10
through the FtsE/X Complex.
AB - The antimicrobial activity of the chemokine CXCL10 against vegetative cells of
Bacillus anthracis occurs via both bacterial FtsE/X-dependent and-independent
pathways. Previous studies established that the FtsE/X-dependent pathway was
mediated through interaction of the N-terminal region(s) of CXCL10 with a
functional FtsE/X complex, while the FtsE/X-independent pathway was mediated
through the C-terminal alpha-helix of CXCL10. Both pathways result in cell lysis
and death of B. anthracis. In other bacterial species, it has been shown that
FtsE/X is involved in cellular elongation though activation of complex-associated
peptidoglycan hydrolases. Thus, we hypothesized that the CXCL10-mediated killing
of vegetative cells of B. anthracis through the FtsE/X-dependent pathway resulted
from the disruption of peptidoglycan processing. Immunofluorescence microscopy
studies using fluorescent peptidoglycan probes revealed that incubation of B.
anthracis Sterne (parent) strain with CXCL10 or a C-terminal truncated CXCL10
(CTTC) affected peptidoglycan processing and/or incorporation of precursors into
the cell wall. B. anthracis DeltaftsX or ftsE(K123A/D481N) mutant strains, which
lacked a functional FtsE/X complex, exhibited little to no evidence of disruption
in peptidoglycan processing by either CXCL10 or CTTC. Additional studies
demonstrated that the B. anthracis parent strain exhibited a statistically
significant increase in peptidoglycan release in the presence of either CXCL10 or
CTTC. While B. anthracis DeltaftsX strain showed increased peptidoglycan release
in the presence of CXCL10, no increase was observed with CTTC, suggesting that
the FtsE/X-independent pathway was responsible for the activity observed with
CXCL10. These results indicate that FtsE/X-dependent killing of vegetative cells
of B. anthracis results from a loss of cell wall integrity due to disruption of
peptidoglycan processing and suggest that FtsE/X may be an important
antimicrobial target to study in the search for alternative microbial
therapeutics.
PMID- 28496438
TI - Identification of Cleavage Sites Recognized by the 3C-Like Cysteine Protease
within the Two Polyproteins of Strawberry Mottle Virus.
AB - Strawberry mottle virus (SMoV, family Secoviridae, order Picornavirales) is one
of several viruses found in association with strawberry decline disease in
Eastern Canada. The SMoV genome consists of two positive-sense single-stranded
RNAs, each encoding one large polyprotein. The RNA1 polyprotein (P1) includes the
domains for a putative helicase, a VPg, a 3C-like cysteine protease and an RNA
dependent RNA polymerase at its C-terminus, and one or two protein domains at its
N-terminus. The RNA2 polyprotein (P2) is predicted to contain the domains for a
movement protein (MP) and one or several coat proteins at its N-terminus, and one
or more additional domains for proteins of unknown function at its C-terminus.
The RNA1-encoded 3C-like protease is presumed to cleave the two polyproteins in
cis (P1) and in trans (P2). Using in vitro processing assays, we systematically
scanned the two polyproteins for cleavage sites recognized by this protease. We
identified five cis-cleavage sites in P1, with cleavage between the putative
helicase and VPg domains being the most efficient. The presence of six protein
domains in the SMoV P1, including two upstream of the putative helicase domain,
is a feature shared with nepoviruses but not with comoviruses. Results from trans
cleavage assays indicate that the RNA1-encoded 3C-like protease recognized a
single cleavage site, which was between the predicted MP and coat protein domains
in the P2 polyprotein. The cleavage site consensus sequence for the SMoV 3C-like
protease is AxE (E or Q)/(G or S).
PMID- 28496439
TI - Bortezomib Warhead-Switch Confers Dual Activity against Mycobacterial
Caseinolytic Protease and Proteasome and Selectivity against Human Proteasome.
AB - Mycobacteria harbor two main degradative proteolytic machineries, the
caseinolytic protease ClpP1P2 and a proteasome. We recently showed that
Bortezomib inhibits ClpP1P2 and exhibits whole cell activity against
Mycobacterium tuberculosis. Bortezomib, a dipeptide with a boronic acid warhead,
is a human proteasome inhibitor approved for cancer therapy. The boronic acid
warhead of the compound has been shown to drive potency against both the human
proteasome and ClpP1P2 protease. Selectivity for the bacterial ClpP1P2 protease
over the human proteasome is lacking but needs to be achieved to move this new
anti-tuberculosis lead forward. In this study we explored whether an alternative
warhead could influence Bortezomib's selectivity. We synthesized an analog
containing a chloromethyl ketone instead of the boronic acid warhead and
determined potencies against the bacterial and human enzymes. Surprisingly, the
analog retained activity against mycobacterial ClpP1P2 and was active against the
mycobacterial proteasome, but was devoid of activity against the human
proteasome. Interrogation of a set of chloromethyl ketone peptides identified
three additional compounds similarly inhibiting both ClpP1P2 and the proteasome
in the bacteria while leaving the human proteasome untouched. Finally, we showed
that these compounds display bactericidal activity against M. tuberculosis with
cytotoxicity ranging from acceptable to undetectable. These results suggest that
selectivity over the human proteasome is achievable. Selectivity, together with
dual-targeting of mycobacterial ClpP1P2 and proteasome makes this new scaffold an
attractive starting point for optimization.
PMID- 28496440
TI - FCgamma Chimeric Receptor-Engineered T Cells: Methodology, Advantages,
Limitations, and Clinical Relevance.
AB - For many years, disappointing results have been generated by many investigations,
which have utilized a variety of immunologic strategies to enhance the ability of
a patient's immune system to recognize and eliminate malignant cells. However, in
recent years, immunotherapy has been used successfully for the treatment of
hematologic and solid malignancies. The impressive clinical responses observed in
many types of cancer have convinced even the most skeptical clinical oncologists
that a patient's immune system can recognize and reject his tumor if appropriate
strategies are implemented. The success immunotherapy is due to the development
of at least three therapeutic strategies. They include tumor-associated antigen
(TAA)-specific monoclonal antibodies (mAbs), T cell checkpoint blockade, and TAA
specific chimeric antigen receptors (CARs) T cell-based immunotherapy. However,
the full realization of the therapeutic potential of these approaches requires
the development of strategies to counteract and overcome some limitations. They
include off-target toxicity and mechanisms of cancer immune evasion, which
obstacle the successful clinical application of mAbs and CAR T cell-based
immunotherapies. Thus, we and others have developed the Fc gamma chimeric
receptors (Fcgamma-CRs)-based strategy. Like CARs, Fcgamma-CRs are composed of an
intracellular tail resulting from the fusion of a co-stimulatory molecule with
the T cell receptor zeta chain. In contrast, the extracellular CAR single-chain
variable fragment (scFv), which recognizes the targeted TAA, has been replaced
with the extracellular portion of the FcgammaRIIIA (CD16). Fcgamma-CR T cells
have a few intriguing features. First, given in combination with mAbs, Fcgamma-CR
T cells mediate anticancer activity in vitro and in vivo by an antibody-mediated
cellular cytotoxicity mechanism. Second, CD16-CR T cells can target multiple
cancer types provided that TAA-specific mAbs with the appropriate specificity are
available. Third, the off-target effect of CD16-CR T cells may be controlled by
withdrawing the mAb administration. The goal of this manuscript was threefold.
First, we review the current state-of-the-art of preclinical CD16-CR T cell
technology. Second, we describe its in vitro and in vivo antitumor activity.
Finally, we compare the advantages and limitations of the CD16-CR T cell
technology with those of CAR T cell methodology.
PMID- 28496442
TI - A Proteomic Study of Hemocyte Proteins from Mud Crab (Scylla paramamosain)
Infected with White Spot Syndrome Virus or Vibrio alginolyticus.
AB - In this study, we investigated the hemocytes' immune response to white spot
syndrome virus (WSSV) or Vibrio alginolyticus infection at the protein level. The
differential proteomes from crab hemocytes infected with WSSV or V. alginolyticus
were analyzed using the isobaric tags for relative and absolute quantitation
approach immediately after infection. Using this approach, we identified 1,799
proteins by their by LC-MS/MS spectra and sequencing data. These included 157
upregulated proteins and 164 downregulated proteins after WSSV infection.
Similarly, 243 proteins were determined to be differentially expressed during V.
alginolyticus infection, of these, 121 were upregulated and 122 were
downregulated after infection. Interestingly, among these differentially
expressed proteins, 106 were up- or downregulated significantly in both WSSV and
V. alginolyticus infection. Six genes, beta-actin, myosin-9, anti
lipopolysaccharide factor isoform 4, anti-lipopolysaccharide factor 4,
transketolase-like protein 2-like isoform 1, and sarcoplasmic calcium-binding
protein 1 were chosen for further study. The expression of these genes all showed
a trend of upregulation at 24 h post-WSSV or V. alginolyticus infection except
for myosin-9 in response to WSSV. To confirm the protective effects of the six
genes, crabs were injected with specific dsRNAs before WSSV or V. alginolyticus
challenge. The results showed that the knockdown of these genes led to an
increase in the morbidity and mortality (P < 0.01) rate, and a decrease in
infection time in WSSV-infected crabs. During the first 84 h, knockdown of these
genes also led to an increase in the morbidity rates in V. alginolyticus
infected crabs, and results of four genes showed a higher mortality rate than
that of the control after they were knocked down. This is the first report of the
proteome response in crab hemocytes during WSSV or V. alginolyticus infection.
These findings will contribute to our understanding of the immune response to
WSSV and V. alginolyticus infection in crabs.
PMID- 28496441
TI - Discovery of Novel Leptospirosis Vaccine Candidates Using Reverse and Structural
Vaccinology.
AB - Leptospira spp. are diderm (two membranes) bacteria that infect mammals causing
leptospirosis, a public health problem with global implications. Thousands of
people die every year due to leptospirosis, especially in developing countries
with tropical climates. Prophylaxis is difficult due to multiple factors,
including the large number of asymptomatic hosts that transmit the bacteria, poor
sanitation, increasing numbers of slum dwellers, and the lack of an effective
vaccine. Several leptospiral recombinant antigens were evaluated as a replacement
for the inactivated (bacterin) vaccine; however, success has been limited. A
prospective vaccine candidate is likely to be a surface-related protein that can
stimulate the host immune response to clear leptospires from blood and organs. In
this study, a comprehensive bioinformatics approach based on reverse and
structural vaccinology was applied toward the discovery of novel leptospiral
vaccine candidates. The Leptospira interrogans serovar Copenhageni strain L1-130
genome was mined in silico for the enhanced identification of conserved beta
barrel (betab) transmembrane proteins and outer membrane (OM) lipoproteins.
Orthologs of the prospective vaccine candidates were screened in the genomes of
20 additional Leptospira spp. Three-dimensional structural models, with a high
degree of confidence, were created for each of the surface-exposed proteins.
Major histocompatibility complex II (MHC-II) epitopes were identified, and their
locations were mapped on the structural models. A total of 18 betab transmembrane
proteins and 8 OM lipoproteins were identified. These proteins were conserved
among the pathogenic Leptospira spp. and were predicted to have epitopes for
several variants of MHC-II receptors. A structural and functional analysis of the
sequence of these surface proteins demonstrated that most betab transmembrane
proteins seem to be TonB-dependent receptors associated with transportation.
Other proteins identified included, e.g., TolC efflux pump proteins, a BamA-like
OM component of the betab transmembrane protein assembly machinery, and the LptD
like LPS assembly protein. The structural mapping of the immunodominant epitopes
identified the location of conserved, surface-exposed, immunogenic regions for
each vaccine candidate. The proteins identified in this study are currently being
evaluated for experimental evidence for their involvement in virulence, disease
pathogenesis, and physiology, in addition to vaccine development.
PMID- 28496443
TI - Higher Levels of Secretory IgA Are Associated with Low Disease Activity Index in
Patients with Reactive Arthritis and Undifferentiated Spondyloarthritis.
AB - INTRODUCTION: Both reactive arthritis (ReA) and undifferentiated
spondyloarthritis (uSpA) belong to the group of autoinflammatory diseases called
spondyloarthritis (SpA). Hypotheses have been proposed about a relationship
between the intestinal mucosa and inflammation of joint tissues. The role of
immunoglobulin IgA or secretory immunoglobulin A (SIgA) in the inflammatory
and/or clinical activity of patients with SpA remains poorly understood.
OBJECTIVE: To evaluate the status of total IgA and SIgA, and the association
among the levels of SIgA, IgA, IgA anti-Chlamydia trachomatis, and anti-Shigella
spp. with the disease activity measures, erythrocyte sedimentation rate (ESR) and
C-reactive protein (CRP) levels, was compared in a cohort of patients with ReA
and uSpA and healthy subjects. METHODS: This was a cross-sectional study. The
serum concentrations of SIgA, IgA anti-C. trachomatis, anti-Shigella spp., and
total IgA were measured. Disease activity was measured in each patient by means
of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing
Spondylitis Disease Activity Score (ASDAS). Statistical analysis did include as
bivariate evaluation, comparisons by Student's t-test, Kruskal-Wallis test, and U
Mann-Whitney test, with a multivariate evaluation by principal components
analysis (PCA). A correlation analysis was carried out using the Pearson
correlation coefficient and a linear regression models. All analysis were made
using Stata version 11.2(r) for Windows, R V3.3.21. Statistical significance was
defined a p-value <0.05. RESULTS: In all, 46 patients (78.2% men; mean age, 34.8
+/- 12.3 years) and 53 controls (41% men; mean age, 32 +/- 11.4 years) were
included in the study. The mean serum levels of SIgA were higher in SpA patients
than in healthy subjects (p < 0.001). Only SIgA levels correlated with disease
activity: BASDAI (r = -0.42, p = 0.0046), ASDAS-CRP (r = -0.37, p = 0.014), and
ASDAS-ESR (r = -0.45, p = 0.0021). The negative correlation between SIgA and all
activity indices was higher in HLA-B27-positive patients (BASDAI r = -0.70, p =
0.0009, ASDAS-CRP r = -0.58, p = 0.0093, and ASDAS-ESR r = -0.57, p = 0.0083).
The PCA showed three factors: the first component was constituted by variables
referred as clinical activity measures, the second did include the serological
activity markers, and the last component was compounded by age and symptoms time.
CONCLUSION: Elevated serum levels of SIgA were found to be related with low
disease activity in patients with ReA and uSpA.
PMID- 28496444
TI - The Transcription Factor c-Maf Promotes the Differentiation of Follicular Helper
T Cells.
AB - Follicular helper T cells (Tfh) have been identified as the primary cell
subpopulation regulating B cell responses in germinal centers, thus supporting
high-affinity antibody production. Among the transcription factors orchestrating
Tfh cell differentiation and function, the role played by the proto-oncogene c
Maf remains poorly characterized. We report herein that selective loss of c-Maf
expression in the T cell compartment results in defective development of Tfh
cells in response to both antigen/adjuvant vaccinations and commensal intestinal
bacteria. Accordingly, c-Maf expression in T cells was essential for the
development and high-affinity antibody secretion in vaccinated animals. c-Maf was
expressed early, concomitantly to BCL6, in Tfh cell precursors and found to
regulate Tfh fate in a cell-autonomous fashion. Altogether, our findings reveal a
novel, non-redundant, function for c-Maf in the differentiation of Tfh cells and
the regulation of humoral immune responses to T-cell-dependent antigens.
PMID- 28496446
TI - Toward an Inclusive, Congruent, and Precise Definition of Autoinflammatory
Diseases.
AB - Autoinflammatory disease was introduced as a concept in 1999, demarcating an
entirely new group of diseases in clinical, immunological, and conceptual terms.
During recent years, the preconditions for the definition of autoinflammatory
conditions have changed. This includes the recent discovery of a number of
monogenic autoinflammatory conditions with complex phenotypes that combine
autoinflammation with defects of the adaptive and/or innate immune system,
resulting in the occurrence of infection, autoimmunity, and/or uncontrolled
hyperinflammation in addition to autoinflammation. Further, there are strong
indications that classical IL-1-driven autoinflammatory diseases are associated
with activation of adaptive immunity. As suggested by this development, we are of
the opinion that an all-encompassing definition of autoinflammatory diseases
should regard autoinflammatory conditions and innate dysregulation as inseparable
and integral parts of the immune system as a whole. Hence, in this article, we
try to advance the conceptual understanding of autoinflammatory disease by,
proposing a modification of the definition by Daniel Kastner et al., which allows
for a congruent and precise description of conditions that expand the
immunological spectrum of autoinflammatory disease.
PMID- 28496448
TI - Corrigendum: ACKR2: An Atypical Chemokine Receptor Regulating Lymphatic Biology.
AB - [This corrects the article on p. 691 in vol. 7, PMID: 28123388.].
PMID- 28496447
TI - Inosine Released from Dying or Dead Cells Stimulates Cell Proliferation via
Adenosine Receptors.
AB - INTRODUCTION: Many antitumor therapies induce apoptotic cell death in order to
cause tumor regression. Paradoxically, apoptotic cells are also known to promote
wound healing, cell proliferation, and tumor cell repopulation in multicellular
organisms. We aimed to characterize the nature of the regenerative signals
concentrated in the micromilieu of dead and dying cells. METHODS: Cultures of
viable melanoma B16F10 cells, mouse fibroblasts, and primary human fibroblast
like synoviocytes (FLS) in the presence of dead and dying cells, their
supernatants (SNs), or purified agonists and antagonists were used to evaluate
the stimulation of proliferation. Viable cell quantification was performed by
either flow cytometry of harvested cells or by crystal violet staining of
adherent cells. High-performance liquid chromatography and liquid chromatography
coupled with mass spectrometry of cell SNs were deployed to identify the nature
of growth-promoting factors. Coimplantation of living cells in the presence of
SNs collected from dead and dying cells and specific agonists was used to
evaluate tumor growth in vivo. RESULTS: The stimulation of proliferation of few
surviving cells by bystander dead cells was confirmed for melanoma cells, mouse
fibroblasts, and primary FLS. We found that small soluble molecules present in
the protein-free fraction of SNs of dead and dying cells were responsible for the
promotion of proliferation. The nucleoside inosine released by dead and dying
cells acting via adenosine receptors was identified as putative inducer of
proliferation of surviving tumor cells after irradiation and heat treatment.
CONCLUSION: Inosine released by dead and dying cells mediates tumor cell
proliferation via purinergic receptors. Therapeutic strategies surmounting this
pathway may help to reduce the rate of recurrence after radio- and chemotherapy.
PMID- 28496449
TI - Differences in Flower Transcriptome between Grapevine Clones Are Related to Their
Cluster Compactness, Fruitfulness, and Berry Size.
AB - Grapevine cluster compactness has a clear impact on fruit quality and health
status, as clusters with greater compactness are more susceptible to pests and
diseases and ripen more asynchronously. Different parameters related to
inflorescence and cluster architecture (length, width, branching, etc.),
fruitfulness (number of berries, number of seeds) and berry size (length, width)
contribute to the final level of compactness. From a collection of 501 clones of
cultivar Garnacha Tinta, two compact and two loose clones with stable differences
for cluster compactness-related traits were selected and phenotyped. Key organs
and developmental stages were selected for sampling and transcriptomic analyses.
Comparison of global gene expression patterns in flowers at the end of bloom
allowed identification of potential gene networks with a role in determining the
final berry number, berry size and ultimately cluster compactness. A large
portion of the differentially expressed genes were found in networks related to
cell division (carbohydrates uptake, cell wall metabolism, cell cycle, nucleic
acids metabolism, cell division, DNA repair). Their greater expression level in
flowers of compact clones indicated that the number of berries and the berry size
at ripening appear related to the rate of cell replication in flowers during the
early growth stages after pollination. In addition, fluctuations in auxin and
gibberellin signaling and transport related gene expression support that they
play a central role in fruit set and impact berry number and size. Other
hormones, such as ethylene and jasmonate may differentially regulate indirect
effects, such as defense mechanisms activation or polyphenols production. This is
the first transcriptomic based analysis focused on the discovery of the
underlying gene networks involved in grapevine traits of grapevine cluster
compactness, berry number and berry size.
PMID- 28496450
TI - High-Density Genetic Map Construction and Gene Mapping of Basal Branching Habit
and Flowers per Leaf Axil in Sesame.
AB - A good genetic map can provide the framework for quantitative trait loci (QTL)
analysis, map-based gene cloning, and genome sequence assembling. The main
objectives of this study were to develop a high-density genetic linkage map using
specific length amplified fragment sequencing (SLAF-seq) in sesame. In the
result, a high-resolution genetic map with 9,378 SLAF markers and 13 linkage
groups (LGs) was constructed. The map spanned a total genetic distance of
1,974.23 cM, and the mean LG length was 151.86 cM, with an average genetic
distance of 0.22 cM between adjacent markers. Based on the newly constructed
genetic map, genes for basal branching habit (SiBH) and flowers per leaf axil
(SiFA) were mapped to LG5 and LG11, respectively.
PMID- 28496445
TI - Eosinophils in Autoimmune Diseases.
AB - Eosinophils are multifunctional granulocytes that contribute to initiation and
modulation of inflammation. Their role in asthma and parasitic infections has
long been recognized. Growing evidence now reveals a role for eosinophils in
autoimmune diseases. In this review, we summarize the function of eosinophils in
inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune
myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with
polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil
targeted therapies, and experimental models have contributed to our understanding
of the regulation and function of eosinophils in these diseases. By examining the
role of eosinophils in autoimmune diseases of different organs, we can identify
common pathogenic mechanisms. These include degranulation of cytotoxic granule
proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of
proteases degrading extracellular matrix, immune modulation through cytokines,
antigen presentation, and prothrombotic functions. The association of
eosinophilic diseases with autoimmune diseases is also examined, showing a
possible increase in autoimmune diseases in patients with eosinophilic
esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we
summarize key future research needs.
PMID- 28496452
TI - Transcriptome Analyses Reveal Candidate Pod Shattering-Associated Genes Involved
in the Pod Ventral Sutures of Common Vetch (Vicia sativa L.).
AB - The seed dispersion caused by pod shattering is a form of propagation used by
many wild species. Loss of seeds from pod shattering is frequent in the common
vetch (Vicia sativa L.), an important self-pollinating annual forage legume.
However, pod shattering is one of the most important defects that limits the
reproduction of the vetch in the field and the usage as a leguminous forage crop.
To better understand the vetch pod shattering mechanism, we used high-throughput
RNA sequencing to assess the global changes in the transcriptomes of the pod
ventral sutures of shattering-susceptible and shattering-resistant vetch
accessions screened from 541 vetch germplasms. A total of 1,285 significantly
differentially expressed unigenes (DEGs) were detected, including 575 up
regulated unigenes and 710 down-regulated unigenes. Analyses of Gene Ontology and
KEGG metabolic enrichment pathways of 1,285 DEGs indicated that 22 DEGs encoding
cell wall modifications and hydrolases associated with pod shattering were highly
expressed in shattering-susceptible accessions. These genes were mainly enriched
in "hydrolase activity," "cytoplasm," and "carbohydrate metabolic process"
systems. These cell wall modifications and hydrolases genes included beta
glucosidase and endo-polygalacturonase, which work together to break down the
glycosidic bonds of pectin and cellulose, and to promote the dissolution and
disappearance of the cell wall in the ventral suture of the pod and make the pod
more susceptible to shattering. We demonstrated the differences in gene
transcription levels between the shattering-susceptible and shattering-resistant
vetch accessions for the first time and our results provided valuable information
for the identifying and characterizing of pod shattering regulation networks in
vetch. This information may facilitate the future identification of pod
shattering-related genes and their underlying molecular mechanisms in the common
vetch.
PMID- 28496451
TI - Genome-Wide Identification of Histone Modifiers and Their Expression Patterns
during Fruit Abscission in Litchi.
AB - Modifications to histones, including acetylation and methylation processes, play
crucial roles in the regulation of gene expression in plant development as well
as in stress responses. However, limited information on the enzymes catalyzing
histone acetylation and methylation in non-model plants is currently available.
In this study, several histone modifier (HM) types, including six histone
acetyltransferases (HATs), 11 histone deacetylases (HDACs), 48 histone
methyltransferases (HMTs), and 22 histone demethylases (HDMs), are identified in
litchi (Litchi chinensis Sonn. cv. Feizixiao) based on similarities in their
sequences to homologs in Arabidopsis (A. thaliana), tomato (Solanum
lycopersicum), and rice (Oryza sativa). Phylogenetic analyses reveal that HM
enzymes can be grouped into four HAT, two HDAC, two HMT, and two HDM subfamilies,
respectively, while further expression profile analyses demonstrate that 17 HMs
were significantly altered during fruit abscission in two field treatments.
Analyses reveal that these genes exhibit four distinct patterns of expression in
response to fruit abscission, while an in vitro assay was used to confirm the
HDAC activity of LcHDA2, LcHDA6, and LcSRT2. Our findings are the first in-depth
analysis of HMs in the litchi genome, and imply that some are likely to play
important roles in fruit abscission in this commercially important plant.
PMID- 28496453
TI - Grapevine Grafting: Scion Transcript Profiling and Defense-Related Metabolites
Induced by Rootstocks.
AB - Rootstocks are among the main factors that influence grape development as well as
fruit and wine composition. In this work, rootstock/scion interactions were
studied using transcriptomic and metabolic approaches on leaves of the
"Gaglioppo" variety, grafted onto 13 different rootstocks growing in the same
vineyard. The whole leaf transcriptome of "Gaglioppo" grafted onto five selected
rootstocks showed high variability in gene expression. In particular, significant
modulation of transcripts linked to primary and secondary metabolism was
observed. Interestingly, genes and metabolites involved in defense responses
(e.g., stilbenes and defense genes) were strongly activated particularly in the
GAG-41B combination, characterized in addition by the down-regulation of abscisic
acid (ABA) metabolism. On the contrary, the leaves of "Gaglioppo" grafted onto
1103 Paulsen showed an opposite regulations of those transcripts and metabolites,
together with the greater sensitivity to downy mildew in a preliminary in vitro
assay. This study carried out an extensive transcriptomic analysis of rootstock
effects on scion leaves, helping to unravel this complex interaction, and
suggesting an interesting correlation among constitutive stilbenes, ABA compound,
and disease susceptibility to a fungal pathogen.
PMID- 28496454
TI - Expression Analyses of Embryogenesis-Associated Genes during Somatic
Embryogenesis of Adiantum capillus-veneris L. In vitro: New Insights into the
Evolution of Reproductive Organs in Land Plants.
AB - An efficient in vitro regeneration system via somatic embryogenesis (SE) was
developed for a fern species Adiantum capillus-veneris. Adventitious shoots,
green globular bodies (GGBs) and calli were obtained with the maximal induction
rate on the Murashige and Skoog (MS) medium of low concentrations of 6
benzyladenine (BA) (0-1.0 mg/L), 2.0 mg/L BA without 2,4-dichlorophenoxyacetic
acid (2,4-D), 0.5 mg/L 2,4-D and 0.5-1.0 mg/L 6-BA, respectively. Cyto
morphological and histological changes in the shoot development via calli and
GGBs were examined. For a better understanding of these developmental events,
expression patterns of six genes, AcLBD16, AcAGL, AcBBM, AcWUS, AcRKD, and
AcLEC1, were characterized during SE. AcBBM and AcLEC1 were ubiquitously
expressed in direct SE (adventitious shoots and GGBs) the maximal expression of
AcBBM in mature GGBs, and the high expression of AcLEC1 in GGB initiation and
adventitious shoots. During the indirect SE, AcLBD16, AcLEC1, AcRKD, and AcWUS
were highly expressed in mature calli. Additionally, phylogenetic analyses showed
that AcWUS, AcBBM, AcLBD, AcAGL, AcRKD, and their homologs of other green plants
formed monophyletic clades, respectively. Some of these gene families, however,
diversified rapidly with the occurrence of embryophytes, suggesting that
embryogenesis-associated genes could experience a rapid evolution with the
colonization of plants to terrestrial environments. Expression and phylogenetic
analyses of those embryogenesis-associated genes by the aid of in vitro
regeneration system of A. capillus-veneris provide new insights into the
evolution of reproductive organs in land plants.
PMID- 28496455
TI - Comparative Proteomic Analysis of the Graft Unions in Hickory (Carya cathayensis)
Provides Insights into Response Mechanisms to Grafting Process.
AB - Hickory (Carya cathayensis), a tree with high nutritional and economic value, is
widely cultivated in China. Grafting greatly reduces the juvenile phase length
and makes the large scale cultivation of hickory possible. To reveal the response
mechanisms of this species to grafting, we employed a proteomics-based approach
to identify differentially expressed proteins in the graft unions during the
grafting process. Our study identified 3723 proteins, of which 2518 were
quantified. A total of 710 differentially expressed proteins (DEPs) were
quantified and these were involved in various molecular functional and biological
processes. Among these DEPs, 341 were up-regulated and 369 were down-regulated at
7 days after grafting compared with the control. Four auxin-related proteins were
down-regulated, which was in agreement with the transcription levels of their
encoding genes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis
showed that the 'Flavonoid biosynthesis' pathway and 'starch and sucrose
metabolism' were both significantly up-regulated. Interestingly, five flavonoid
biosynthesis-related proteins, a flavanone 3-hyfroxylase, a cinnamate 4
hydroxylase, a dihydroflavonol-4-reductase, a chalcone synthase, and a chalcone
isomerase, were significantly up-regulated. Further experiments verified a
significant increase in the total flavonoid contents in scions, which suggests
that graft union formation may activate flavonoid biosynthesis to increase the
content of a series of downstream secondary metabolites. This comprehensive
analysis provides fundamental information on the candidate proteins and secondary
metabolism pathways involved in the grafting process for hickory.
PMID- 28496456
TI - Swallowing Disorders after Oral Cavity and Pharyngolaryngeal Surgery and Role of
Imaging.
AB - Head and neck squamous cell carcinoma is the sixth most common cancer diagnosed
worldwide and the eighth most common cause of cancer death. Malignant tumors of
the oral cavity, oropharynx, and larynx can be treated by surgical resection or
radiotheraphy with or without chemotheraphy and have a profound impact on quality
of life functions, including swallowing. When surgery is the chosen treatment
modality, the patient may experience swallowing impairment in the oral and
pharyngeal phases of deglutition. A videofluoroscopic study of swallow enables
the morphodynamics of the pharyngeal-esophageal tract to be accurately examined
in patients with prior surgery. These features allow an accurate tracking of the
various phases of swallowing in real time, identifying the presence of functional
disorders and of complications during the short- and long-term postoperative
recovery. The role of imaging is fundamental for the therapist to plan
rehabilitation. In this paper, the authors aim to describe the videofluoroscopic
study of swallow protocol and related swallowing impairment findings in
consideration of different types of surgery.
PMID- 28496457
TI - Trends in Iran Pharmaceutical Market.
PMID- 28496458
TI - Preparation, Optimization and Toxicity Evaluation of (SPION-PLGA) +/-PEG
Nanoparticles Loaded with Gemcitabine as a Multifunctional Nanoparticle for
Therapeutic and Diagnostic Applications.
AB - The aim of this study was to develop a novel multifunctional nanoparticle, which
encapsulates SPION and Gemcitabine in PLGA +/- PEG to form multifunctional drug
delivery system. For this aim, super paramagnetic iron oxide nanoparticles
(SPIONs) were simultaneously synthesized and encapsulated with Gemcitabine (Gem)
in PLGA +/- PEG copolymers via W/O/W double emulsification method. Optimum size
and encapsulation efficiency for radiosensitization, hyperthermia and diagnostic
applications were considered and the preparation parameters systematically were
investigated and physicochemical characteristics of optimized nanoparticle were
studied. Then SPION-PLGA and PLGA-Gem nanoparticles were prepared with the same
optimized parameters and the toxicity of these nanoparticles was compared with
Gemcitabine in human breast cancer cell line (MCF-7). The optimum preparation
parameters were obtained with Gem/polymer equal to 0.04, SPION/polymer equal to
0.8 and 1% sucrose per 20 mg of polymer. The hydrodynamic diameters of all
nanoparticles were under 200 nm. Encapsulation efficiency was adjusted between
13.2% to 16.1% for Gemcitabine and 48.2% to 50.1% for SPION. In-vitro Gemcitabine
release kinetics had controlled behavior. Enhancement ratios for PLGA-Gem and
SPION-PLGA-Gem at concentration of nanoparticles equal to IC50 of Gemcitabine
were 1.53 and 1.89 respectively. The statistical difference was significant (p
value = 0.006 for SPION-PLGA-Gem and p-value = 0.015 for PLGA-Gem compared with
Gemcitabine). In conclusion, we have successfully developed a Gemcitabine loaded
super paramagnetic PLGA-Iron Oxide multifunctional drag delivery system. Future
work includes in-vitro and in-vivo investigation of radiosensitization and other
application of these nanoparticles.
PMID- 28496459
TI - Fabrication and in-vitro Evaluation of Ketotifen Fumarate-loaded PLGA
Nanoparticles as a Sustained Delivery System.
AB - Ketotifen fumarate is a non-bronchodilator anti-asthmatic drug which inhibits the
effects of certain endogenous substances known to be inflammatory mediators, and
thereby exerts antiallergic activity. The present study describes the formulation
of a sustained release nanoparticle (NP) drug delivery system containing
ketoftifen, using poly (D,L lactide-co-glycolide) acid (PLGA). Biodegradable NPs
were prepared using 50 : 50 PLGA by a water in-oil-in-water (w/o/w) double
emulsion-solvent evaporation procedure and characterized for drug content, DSC
(differential scanning calorimetry, XRD (X-ray diffractionl), FTIR (Fourier
transform spectroscopy), particle size , surface morphology using scanning
electron microscopy, and drug release rate. The effects of different drug-to
polymer ratios on the characteristics of the NPs were investigated. NPs prepared
were spherical with a smooth surface. Size of NPs was dependent on the
concentration of polymer (10 mg/mL, 754.6 nm). Increasing the external organic
phase volume (primary emulsion) resulted in larger particles with higher
encapsulation efficiency (55%). The best drug to polymer ratio in the NP was F3
(1:10 ratio) which showed loading efficiency of 55%, and mean particle size of
754.6 nm, respectively. The FTIR, XRPD, and DSC results ruled out any chemical
interaction between the drug and PLGA. The NPs prepared with low ratio of drug to
polymer (1:5) F1 formulation showed faster dissolution rate than those with high
drug to polymer ratio (1:10) F3 formulation. In conclusion, by selecting an
appropriate level of the investigated parameters, spherical NPs with
encapsulation efficiencies higher than 55% and a prolonged drug release over 24h
(73.67-90.05%) were obtained.
PMID- 28496460
TI - Doxorubicin Loaded DNA Aptamer Linked Myristilated Chitosan Nanogel for Targeted
Drug Delivery to Prostate Cancer.
AB - Recently, specific attention has been paid to aptamers, short DNA or RNA, as a
tool for cancer diagnosis and therapy. In the present study MCS nanogels were
prepared by Myristate: Chitosan at 1:9 ratio and were characterized by several
techniques. A selected ssDNA aptamer (Apt) capable of detecting LNCaP cells was
linked to Myristilated Chitosan nanogels (Apt-MCS) by glutaraldehyde and loaded
with Doxorubicin (DOX) to be used in targeted drug delivery against the Prostate
cancer cells. LNCaP and PC-3 cells were treated with Apt-MCS-DOX complex and the
binding efficiency was estimated by flow cytometry. The binding affinity of the
selected aptamers was above 70% compared to the initial library. The loading
capacity of the nanogel was as high as 97% and up to 40% of DOX were released
from MCS within 15 days. Cytotoxicity of nanodrug on LNCaP cells was determined
by MTT assay. Apt-MCS-DOX was specifically binded to LNCaP cells whereas it
didn't show any specificity to PC-3 cells as a negative control. Both MCS-DOX and
Apt-MCS-DOX showed a lethal effect on LNCaP cells. Our results can lead to an
aptamer based simple and applicable technique for early diagnosis and treatment
of cancerous cells.
PMID- 28496461
TI - Simultaneous Optimization of Multiple Response Variables for the Gelatin-chitosan
Microcapsules Containing Angelica Essential Oil.
AB - Angelica essential oil (AO), a major pharmacologically active component of
Angelica sinensis (Oliv.) Diels, possesses hemogenesis, analgesic activities, and
sedative effect. The application of AO in pharmaceutical systems had been limited
because of its low oxidative stability. The AO-loaded gelatin-chitosan
microcapsules with prevention from oxidation were developed and optimized using
response surface methodology. The effects of formulation variables (pH at complex
coacervation, gelatin concentration, and core/wall ratio) on multiple response
variables (yield, encapsulation efficiency, antioxidation rate, percent of drug
released in 1 h, and time to 85% drug release) were systemically investigated. A
desirability function that combined these five response variables was
constructed. All response variables investigated were found to be highly
dependent on the formulation variables, with strong interactions observed between
the formulation variables. It was found that optimum overall desirability of AO
microcapsules could be obtained at pH 6.20, gelatin concentration 25.00%, and
core/wall ratio 40.40%. The experimental values of the response variables highly
agreed with the predicted values. The antioxidation rate of optimum formulation
was approximately 8 times higher than that of AO. The in-vitro drug release from
microcapsules was followed Higuchi model with super case-II transport mechanism.
PMID- 28496462
TI - Synthesis and Characterization of Biodegradable Semi-Interpenetrating Polymer
Networks Based on Star-Shaped Copolymers of E-Caprolactone and Lactide.
AB - In this paper, the focus is on a new kind of biodegradable semi-interpenetrating
polymer networks, which is derived from E-caprolactone, lactide, 1,4-butane
diisocyanate and ethylenediamine and also its potential has been investigated in
soft tissue engineering applications. The polymers were characterized by nuclear
magnetic resonance (NMR) spectrometry, Fourier transform infrared spectroscopy
(FT-IR), differential thermal analysis (DTA), differential scanning calorimetry
(DSC), and thermogravimetric analysis (TGA). These experiments show that the
polymers with the right composition and the expected molecular weight were
achieved. Also, the in-vitro degradation of polymer network was examined in
phosphate buffer solutions (pH 7.4) at 37 degrees C. Moreover, cell viability
and adhesion tests were carried out with fibroblast cells by the MTT assay, which
confirmed biocompatibility. Polyurethane materials have superior mechanical
properties, so these biodegradable and biocompatible films demonstrate potential
for future application as cell scaffolds in soft tissue engineering applications.
PMID- 28496463
TI - Antibacterial Loaded Spray Dried Chitosan Polyelectrolyte Complexes as Dry Powder
Aerosol for the Treatment of Lung Infections.
AB - Inhalation delivery of aerosolized antibacterials is preferred over conventional
methods of delivery for targeting lung infection. The present study is concerned
with the development and characterization of a novel, spray dried, aerosolized,
chitosan polyelectrolyte complex (PEC) based microparticles containing
antibacterials for the treatment of lung infections. Chitosan polyelectrolyte
complex microparticles were formulated by spray drying process. Prepared spray
dried chitosan PEC microparticles were studied for surface morphology, drug
encapsulation efficiency, moisture content, Carr's index, solid state interaction
by XRD, aerosolization behaviour and in-vitro drug release. In-vitro cytotoxicity
studies of microparticles were carried out on H1299 alveolar cell lines.
Antibacterial efficacy of microparticles was assessed on the basis of
determination of pharmacokinetic parameters in bronchial alveolar lavage (BAL) of
rats using PK/PD analysis. The PEC microparticles were mostly spherical and
exhibited high drug encapsulation efficiency. Release profiles showed an initial
burst phase followed by a secondary sustained release phase. Good aerosolization
behaviour as dry powder inhaler was demonstrated by microparticles with high
values of recovered dose, emitted dose, and fine particle fraction. No overt
cytotoxicity of microparticles was detected against H1299 alveolar cell line.
More than 8 to 9 folds higher Cmax values were obtained in BAL fluid with
microparticles as compared to intravenously administered antibacterial solution.
The findings of the study suggest that chitosan polyelectrolyte complex based
microparticles as dry powder inhaler can be an efficient antibacterial delivery
system for sustained and effective management of lung infection.
PMID- 28496464
TI - Using beta-cyclodextrin and Arabic Gum as Wall Materials for Encapsulation of
Saffron Essential Oil.
AB - Saffron essential oil has a pleasant aroma and medicinal activities. However, it
is sensible into the environmental condition. Therefore, it should be protected
against unwanted changes during storage or processing. Encapsulation is
introduced as a process by which liable materials are protected from unwanted
changes. In the present study, different ratios (0:100, 25:75, 50:50, 75:25, and
100:0) of beta-cyclodextrin (beta-CD) and arabic gum (GA) were used as wall
martial for encapsulation saffron essential oil. In order to calculate of loading
capacity (LC) and encapsulation efficiency (EE), and release (RE), safranal was
determined as indicator of saffron essential oil using GC. According to the
results, the highest LC and EE were related to the mixture of beta-CD/GA at a
75:25 ratio. In contrast, the lowest encapsulate hygroscopicity (EH) and RE were
observed when only beta-CD was applied as wall material (P<=0.05). Comparing the
differential scanning calorimetry (DSC) thermograms of the control and
encapsulate of beta-CD/GA (75:25) confirmed encapsulation of saffron essential
oil. Scanning electron microscopy (SEM) images with high magnifications showed
the rhombic structure that partially coated by GA. The mixture of beta-CD/GA at a
75:25 ratio can be recommended for saffron essential oil encapsulation.
PMID- 28496465
TI - Effect of Nonionic Surfactants (Dodecyl Maltoside and Polysorbate 20) on
Prevention of Aggregation and Conformational Changes of Recombinant Human
IFNbeta_1b Induced by Light.
AB - Liquid protein formulations are prone to form aggregates. The effect of nonionic
surfactants such as Polysorbate 20 (PS 20) and n-Dodecyl beta-D-maltoside (DDM)
on the prevention of aggregation and conformational changes of recombinant human
IFNbeta-1b (rhIFN beta_1b) was explored. Polysorbate has been used in
formulations of protein pharmaceuticals. There have been concerns about using PS
20 due to its residual peroxide content which may negatively affect protein
efficacy. n-Dodecyl beta-D-maltoside has been of interest and shown to be highly
effective in prevention of aggregation. Fresh bulk of rhIFN beta_1b was
formulated using DDM or different concentrations of PS 20. Formulations were
exposed to light stress condition according to the ICH guideline of Q1b. The
overall conformational integrity of individual samples was characterized by a
combination of Circular dichroism (CD), Fluorescence spectroscopy and RP_HPLC
techniques. The CD spectrum depicting the conformational integrity of rhIFN
beta_1b showed 31.9% and 31.2% decreases in alpha-helix content of protein
samples with 0.2% or 0.02% of PS20 compared to only18.2% of that containing 0.2%
DDM. The RP-HPLC analysis also showed that the oxidized impurity in formulation
containing DDM is less than those contain PS 20. Complementary analysis of the
liquid formulations using IFR and UV methods also was in compliance with the data
obtained by CD. Compared to PS 20, the sample of rhIFN beta_1b formulation with
DDM was more resistant to the destruction effect of light. Results were in
accordance with previous studies and could suggest DDM as a reliable anti
aggregation surfactant in biopharmaceutical formulations.
PMID- 28496466
TI - Validated Spectrophtometric Method for Simultaneous Determination of
Buprenorphine and Naloxone in Pharmaceutical Dosage Forms.
AB - Buprenorphine is a partial mu agonist and kappa antagonist which is used for the
treatment of pain and opioid addiction. A mixture of buprenorphine hydrochloride
and naloxone hydrochloride has been approved for the treatment of opioid
dependence. In this study a third order derivative spectrophotometric method
based on zero-crossing technique has been used for the simultaneous determination
of buprenorphine hydrochloride and naloxone hydrochloride in tablets. The
measurements were carried out at wavelengths of 257.8 (zero-crossing point of
naloxone hydrochloride) and 252.2 nm (zero-crossing point of buprenorphice
hydrochloride) for buprenorphine hydrochloride and naloxone hydrochloride,
respectively in the third order derivative spectra obtained in methanol and 0.1 M
NaOH (50:50) as solvent. The method was found to be linear in the range of 20-80
ug/mL for buprenorphine hydrochloride and 5-20 ug/mL for naloxone hydrochloride.
The within-day and between-day coefficient of variation and error values were
less than 2.5% and 1.8%, respectively. The proposed method was successfully used
for simultaneous determination of these drugs in pharmaceutical dosage form
without any interference from excipients or need to prior separation before
analysis.
PMID- 28496467
TI - Interference-free Determination of Carbamazepine in Human Serum Using High
Performance Liquid Chromatography: A Comprehensive Research with Three-way
Calibration Methods.
AB - In the present study, a comprehensive and systematic strategy was described to
evaluate the performance of several three-way calibration methods on a bio
analytical problem. Parallel factor analysis (PARAFAC), alternating trilinear
decomposition (ATLD), self-weighted alternating trilinear decomposition (SWATLD),
alternating penalty trilinear decomposition (APTLD), and unfolded partial least
squares combined with the residual bilinearization procedure (U-PLS/RBL) were
applied on high performance liquid chromatography with photodiode-array detection
(HPLC-DAD) data to quantify carbamazepine (CBZ) in different serum samples. Using
the proposed approach, successfully quantification of CBZ in human plasma, even
in the presence of diverse uncalibrated serious interfering components was
achieved. Moreover, the accuracy and precision of each algorithm for analyzing
CBZ in serum samples were compared using root mean square error of prediction
(RMSEP), the recovery values and figures of merits and reproducibility of the
analysis. Satisfying recovery values for the analyte of interest were obtained by
HPLC-DAD on a Bonus-RP column using an isocratic mode of elution with
acetonitrile/K2HPO4 (pH = 7.5) buffer solution (45:55) coupled with second-order
calibrations. Decreas of the analysis time and less solvent consumption are some
of the pluses of this method. The analysis of real samples showed that the
modeling of complex chromatographic profiles containing CBZ as the target drug
using any of the mentioned algorithms can be potentially benefit drug monitoring
in therapeutic research.
PMID- 28496468
TI - A Simple and Specific Stability- Indicating RP-HPLC Method for Routine Assay of
Adefovir Dipivoxil in Bulk and Tablet Dosage Form.
AB - A simple and reliable stability-indicating RP-HPLC method was developed and
validated for analysis of adefovir dipivoxil (ADV).The chromatographic separation
was performed on a C18 column using a mixture of acetonitrile-citrate buffer (10
mM at pH 5.2) 36:64 (%v/v) as mobile phase, at a flow rate of 1.5 mL/min.
Detection was carried out at 260 nm and a sharp peak was obtained for ADV at a
retention time of 5.8 +/- 0.01 min. No interferences were observed from its
stress degradation products. The method was validated according to the
international guidelines. Linear regression analysis of data for the calibration
plot showed a linear relationship between peak area and concentration over the
range of 0.5-16 MUg/mL; the regression coefficient was 0.9999and the linear
regression equation was y = 24844x-2941.3. The detection (LOD) and quantification
(LOQ) limits were 0.12 and 0.35 MUg/mL, respectively. The results proved the
method was fast (analysis time less than 7 min), precise, reproducible, and
accurate for analysis of ADV over a wide range of concentration. The proposed
specific method was used for routine quantification of ADV in pharmaceutical bulk
and a tablet dosage form.
PMID- 28496469
TI - Development of an Analytical Method for Dibutyl Phthalate Determination Using
Surrogate Analyte Approach.
AB - Dibutyl phthalate (DBP) is a phthalic acid ester and is widely used in polymeric
products to make them more flexible. DBP is found in almost every plastic
material and is believed to be persistent in the environment. Various analytical
methods have been used to measure DBP in different matrices. Considering the
ubiquitous nature of DBP, the most important challenge in DBP analyses is the
contamination of even analytical grade organic solvents with this compound and
lack of availability of a true blank matrix to construct the calibration line.
Standard addition method or using artificial matrices reduce the precision and
accuracy of the results. In this study a surrogate analyte approach that is based
on using deuterium labeled analyte (DBP-d4) to construct the calibration line was
applied to determine DBP in hexane samples.
PMID- 28496470
TI - QSAR Studying of Oxidation Behavior of Benzoxazines as an Important
Pharmaceutical Property.
AB - In this work the electrooxidation half-wave potentials of some Benzoxazines were
predicted from their structural molecular descriptors by using quantitative
structure-property relationship (QSAR) approaches. The dataset consist the half
wave potential of 40 benzoxazine derivatives which were obtained by DC
polarography. Descriptors which were selected by stepwise multiple selection
procedure are: HOMO energy, partial positive surface area, maximum valency of
carbon atom, relative number of hydrogen atoms and maximum electrophilic reaction
index for nitrogen atom. These descriptors were used for development of multiple
linear regression (MLR) and artificial neural network (ANN) models. The
statistical parameters of MLR model are standard errors of 0.016 and 0.018 for
training and test sets, respectively. Also, these values are 0.012 and 0.017 for
training and test sets of ANN model, respectively. The predictive power of these
models was further examined by leave-eight-out cross validation procedure. The
obtained statistical parameters are Q2 = 0.920 and SPRESS = 0.020 for MLR model
and Q2 = 0.949 and SPRESS = 0.015 for ANN model, which reveals the superiority of
ANN over MLR model. Moreover, the results of sensitivity analysis on ANN model
indicate that the order of importance of descriptors is: Relative number of H
atom > HOMO energy > Maximum electrophyl reaction index for N atom > Partial
positive surface area (order-3) > maximum valency of C atom.
PMID- 28496471
TI - Ionic Liquid-assisted Synthesis of Celexocib Using Tris-(2-hydroxyethyl) Ammonium
Acetate as an Efficient and Reusable Catalyst.
AB - Celecoxib is classified as none traditional nonsteroidal anti-inflammatory drugs
(NSAIDs). This compound has conventional properties of NSAIDs such as anti
inflammatory, analgesic, and antipyretic activities beside reduced risk of
gastrointestinal side effect of traditional NSAIDs such as ibuprofen. This
compound gets a second sale rank of NSAIDs market at 2016 in the world and sales
more than 17000 Kg in Iran during the past 6 month. So, a simple, rapid and green
method for synthesis of this compound is important. In the present study, a novel
green method was suggested for the synthesis of celecoxib using the ionic liquid.
Celecoxib was provided by the reaction of trifluoroacetone, 4
methylbenzoylchloride, and 4-hydrazinobenzenesulfonamide hydrochloride. The tris
(2-hydroxyethyl) ammonium acetate as ionic liquid was prepared by mixing tris-(2
hydroxyethyl) ammonium and acetic acid, and used as an efficient catalyst. The
structure of the synthetic products was confirmed by analytical and spectroscopic
methods including 1HNMR, 13CNMR, IR, MS and elemental analysis. This ionic liquid
can play dual roles in the synthesis of celecoxib, as a catalyst to improve
electrophilicity of carbonyl group and also as a solvent of reaction. The
reaction rate and yield (86%) were improved considerably. Moreover IL showed the
same efficiency when used in 4 consecutive reactions.
PMID- 28496472
TI - Synthesis and Biological Evaluation of N-(5-(pyridin-2-yl)-1,3,4-thiadiazol-2
yl)benzamide Derivatives as Lipoxygenase Inhibitor with Potential Anticancer
Activity.
AB - In the recent years, the role of LOX enzymes in the origin of neoplastic diseases
such as colorectal, skin, pancreatic and renal cancers has been confirmed. A new
series of 1,3,4-thiadiazole derivatives bearing 2-pyridyl moiety was synthesized
and the cytotoxicity of the members of this series was assessed using MTT
protocol. Enzyme inhibitory activity of the prepared compounds was also tested
against 15-lipoxygenase-1 as a novel target for the discovery of anticancer
drugs. PC3, HT29 and SKNMC cell lines were utilized and the obtained results were
compared with doxorubicin. Overall, nitro containing derivatives exerted a higher
cytotoxic activity against PC3 cell line and methoxylated derivatives showed an
acceptable activity against SKNMC cell line. Methoxylated derivatives were also
the most potent enzyme inhibitors especially at position ortho of the phenyl
residue.
PMID- 28496473
TI - Molecular Dynamics and Docking Investigations of Several Zoanthamine-Type Marine
Alkaloids as Matrix Metaloproteinase-1 Inhibitors.
AB - Zoanthamine-type alkaloids display a wide spectrum of biological effects. This
study aimed to examine the inhibitory effects of norzoanthamine and its ten
homologues of zoanthamine class on human fibroblast collagenase by modeling a
three-dimensional structure of the ligands at collagenase using energy
minimization, docking, molecular dynamics simulation and MM-PB/GBSA binding free
energy calculations. The results showed that zoanthamide, zooxathellamine and
enol-iminium form of norzoanthamine, with lower binding free energies than other
compounds, are potent inhibitors of collagenase. However, the enol-iminium form
of norzoanthamine showed a more inhibitory activity against collagenase than its
keto form. This suggests that it can be used for treatment of many diseases such
as osteoporosis, autoimmune diseases, and cancer. Zinc-binding residues such as
His 118, His 122 and His 128 for hydrogen bonds and Leu 81, Tyr 110, Val 115, Leu
126, Pro 138, Ser 139 for hydrophobic interactions should be considered for
designing an inhibitor for collagenase. Our theoretical results and MM/GBSA
binding free energy calculations are consistent with experimental studies.
PMID- 28496474
TI - Enhancement of Antinociceptive Effect by Co-administration of Amitriptyline and
Crocus Sativus in a Rat Model of Neuropathic Pain.
AB - The aim of this study was to evaluate the anti-nociceptive effects of a low, sub
effective dose of amitriptyline, in combination with the different doses of
ethanolic and aqueous extracts of Crocus sativus following sciatic nerve chronic
constriction injury (CCI) in rats. Amitriptyline (3, 10 and 30 mg/Kg, i.p.) and
the extracts (25, 50 and 100 mg/Kg, i.p.), were separately administered at the
time of CCI for 7 consecutive days. In combination therapy, the sub
antinociceptive dose of amitriptyline (3 mg/Kg) was given with the three
different doses of extracts for seven days. Mechanical allodynia, thermal
allodynia and thermal hyperalgesia were evaluated by von Frey, acetone and
radiant heat tests, respectively, 1 day before and on days 3, 5 and 7 after
surgery. Co-administration of amitriptyline (3 mg/Kg) with aqueous extract (50,
100 mg/Kg,) produced more potent cold anti-allodynic (P < 0.01 and P < 0.001,
respectively) as well as thermal anti-hyperalgesic (P < 0.05) effects than that
produced by each of them. Amitriptyline (3 mg/Kg) plus ethanolic extract (50, 100
mg/Kg) produced more potent cold anti-allodynic (P < 0.05 and P < 0.001,
respectively) as well as thermal anti-hyperalgesic (P < 0.05) effects as compared
with the sum effects produced by each of them. Mechanical anti-allodynia effect
was only potentiated with the co-administration of amitriptyline with the high
dose of aqueous extract (100 mg/Kg, P < 0.001). Our study supports the use of
saffron as an adjunctive to amitriptyline to improve the therapeutic outcome in
the management of neuropathic pain.
PMID- 28496475
TI - The Effect of Green Tea Extract on Oxidative Stress and Spatial Learning in
Streptozotocin-diabetic Rats.
AB - : Diabetes mellitus is associated with distribution of cognitive functioning.
Hyperglycemia induced oxidative stress has been proposed as a cause of memory
complications of diabetes including cognitive impairment. The aim of this study
was to examine total green tea extract (TGTE), a potent free radical scavenger
against spatial impairment in Streptozotocin-diabetic rats. Eight weeks after
diabetes induction, TGTE was administrated throught drinking water 3 mg/L. The
learning and memory behavior was evaluated with Morris water maze task in male
rats. Then, for estimation of oxidative stress parameters such as lipid
peroxidation (LPO), total antioxidant capacity (FRAP) and total thiol groups in
blood were measured. The total green tea extract showed improved cognitive
impairment in diabetic groups but these changes weren't significant. There was
also significant increase FRAP level and total thiol groups in treated green tea
groups vs. CONTROL: group. This study demonstrated the effectiveness of TGTE on
spatial impairment and oxidative stress induced in diabetes mellitus.
PMID- 28496476
TI - In-vitro Antioxidant, Cytotoxic, Cholinesterase Inhibitory Activities and Anti
Genotoxic Effects of Hypericum retusum Aucher Flowers, Fruits and Seeds Methanol
Extracts in Human Mononuclear Leukocytes.
AB - The present study investigates the antioxidant, anticancer, anticholinesterase,
anti-genotoxic activities and phenolic contents of flower, fruit and seed
methanol extracts of Hypericum retusum AUCHER. The amounts of protocatechuic
acid, catechin, caffeic acid and syringic acid in methanol extracts were
determined by HPLC. Total phenolic content of H. retusum seed extract was found
more than fruit and flower extracts. The DPPH free radical scavenging activity of
flower and seed methanol extracts showed close activity versus BHT as control.
Among three extracts of H. retusum only flower methanol extract was exhibited
considerable cytotoxic activities against to HeLa and NRK-52E cell lines.
Moreover, seed methanol extract showed both acetyl and butyrl-cholinesterase
inhibitory activity. The highest anti-genotoxic effects were seen 25 and 50
MUg/mL concentrations. In this study, the extracts showed a strong antioxidant
and anti-genotoxic effect. The seed extract was more efficient- than extracts of
fruit and flowers. Our results suggest that the antioxidant and anti-genotoxic
effects of extracts depend on their phenolic contents. Further studies should
evaluate the in-vitro and in-vivo the benefits of H. retusum seed methanol
extracts.
PMID- 28496477
TI - Cytotoxic Properties of Three Isolated Coumarin-hemiterpene Ether Derivatives
from Artemisia armeniaca Lam.
AB - Considering multiple reports on cytotoxic activity of the Artemisia genus and its
phytochemicals, in the current study A. armeniaca Lam. and the three components
isolated from the plant were subjected to cytotoxic studies. Analytical
fractionation of A. armeniaca aerial parts for the first time was directed to the
isolation of 7-hydroxy-8-(4-hydroxy-3-methylbutoxy) comarin (armenin), 8-hydroxy
7-(4-hydroxy-3-methylbutoxy) comarin (isoarmenin) and deoxylacarol. Cytotoxicity
assessed with alamalBlue(r) assay and apoptosis was detected by PI staining and
western blot analysis of Bax and PARP proteins. Extracts and all compounds
exhibited cytotoxic activity against apoptosis-proficient HL-60 and apoptosis
resistant K562 cells, with the lowest cytotoxic activity on J774 cell line as non
malignant cell. Armenin as the most potent component decreased the viability of
cell with IC50 of 22.5 and 71.1 uM for K562 and HL-60 cells respectively and
selected for further mechanistic study. Armenin increased the sub-G1 peak in flow
cytometry histogram of HL-60 and K562 treated cells and increase in the amount of
Bax protein and the cleavage of PARP in comparison with the control after
treatment for 48 h in K562 treated cells verified the apoptotic activity of the
armenin. Taken together, according to the finding of this study armenin was
introduced as a novel cytotoxic compound with apoptotic activity, which is
encouraging for further mechanistic and clinical studies.
PMID- 28496478
TI - Study of Crocin & Radiotherapy-induced Cytotoxicity and Apoptosis in the Head and
Neck Cancer (HN-5) Cell Line.
AB - Malignant tumors of head and neck carcinomas are the sixth most common type of
cancer. Current systemic therapies for cancer show side effects in normal tissues
and short-term efficacy due to drug resistance. Consequently, there is much
interest in identifying new drugs for cancer treatment. Crocin (an active
ingredient of saffron) has been shown to have cytotoxic effects on cancer cell
lines. Chemo radiotherapy is the standard treatment for head and neck cancer. In
the present study, the cytotoxic effects, inducing apoptosis and the radiation
sensitivity of crocin were evaluated in the head and neck cancer cell line (HN
5). HN-5 cells were cultured in a DMEM medium and incubated with different
concentrations of crocin (12.5-1000 ug/mL). They were exposed to 2 Gy gamma-rays.
Cell viability was quantified by the MTT assay. Apoptotic cells were determined
using PI staining of DNA fragmentation by flowcytometry (sub-G1 peak). Crocin
decreased cell viability in HN-5 cells in a time and concentration dependent
manner. Crocin also induced a sub-G1 peak in the flowcytometery histogram of
treated cells compared with the control, suggesting that apoptotic cell death is
caused by its toxicity. Crocin was also shown to sensitize cells to radiation
induced toxicity and apoptosis. The simultaneous use of crocin and radiation
therefore increases radiation sensitivity and cell death. Thus, after further
study crocin can be considered as a potential drug and sensitizer in cancer
treatment.
PMID- 28496479
TI - A Comparison of Hepatocyte Cytotoxic Mechanisms for Docetaxel and PLGA-Docetaxel
Nanoparticls.
AB - Docetaxel (DTX) is one of the most widely used drugs in oncology due to its high
efficacy against several cancers. Though, its routine clinical administration,
formulated in tween 80, causes serious side effects. Polylactide-co-glycolide
(PLGA), biodegradable polyester synthesized and approved for human use, is
employed to overcome these problems. In this investigation, we compare the
cytotoxic mechanisms of DTX and PLGA-DTX in isolated rat hepatocytes.
Cytotoxicity of DTX and PLGA-DTX were associated with reactive oxygen species
formation, activation of caspases cascade, collapse of mitochondrial membrane
potential (MMP), lysosomal membrane leakiness and ATP depletion. Our results also
showed that CYP2E1 is involved in the oxidative stress cytotoxicity mechanism and
both drugs are detoxified via phase II metabolic methylation. Furthermore, we
concluded that PLGA-DTX is bioactivated by GSH. It could also potentiate
hepatocyte toxicity through a mitochondrial/lysosomal toxic cross-talk. In
addition to these observed differences, it is likely that mode of hepatocyte
membrane penetration is different between these compounds.
PMID- 28496480
TI - In-vitro Pro Apoptotic Effect of Crude Saponin from Ophiocoma erinaceus against
Cervical Cancer.
AB - Ophiocoma erinaceus Muller &Troschel (Ophiocomidae) is part of the extensive
group of echinoderm that contains bioactive metabolites. As the anti cancer
potential of brittle star saponin has not been reported against cervical cancer,
the present study was conducted to evaluate the anticancer effect of extracted
crude saponin. Saponin extraction was conducted using conventional method such as
froth test, TLC, FTIR and erythrolysis assay. The Hela-S3 cervical carcinoma and
HNCF-PI52 normal cells were treated with different concentrations of saponin
fraction for 24 and 48 h. The cytotoxicity was examined by MTT, DAPI, AO/PI,
Annexin V-FITC and flow cytometry. In addition, the apoptotic induced pathway was
studied using caspase assay, evaluation of ROS generation and Bcl-2 mRNA level.
Crude saponin showed cytotoxic properties in Hela-S3 cells (IC50of 23.4 ug/mL)
without significant impact against normal cells. In addition, the crude saponin
increased sub-G1 peak in flow cytometry histogram of treated cells, ROS
generation and caspase-3 and -9 activity (IC50 of 11.10, 11.27 ug/mL). The dose
dependent down regulation of Bcl-2 in treated cells demonstrated that saponin
fraction can trigger intrinsic apoptotic pathway in cancer cells. This study
provides valuable information about the apoptotic inducing effect of saponin
fraction, which can offer new insights into the anticancer potential of saponin
as a promising candidate against human cervical carcinoma.
PMID- 28496481
TI - Evaluation of Various Biological Activities of the Aerial Parts of Scrophularia
frigida Growing in Iran.
AB - The current study was assigned to evaluate the total phenol, total flavonoid
content (TPC, TFC) and antioxidant properties of extracts from the aerial parts
of Scrophularia frigida (S. frigida). Extracts were also tested by preliminary
phytochemical screening as well as cytotoxic activity against Artemia salina, MCF
7 (human breast carcinoma) and SW-480 (colon carcinoma) and L-929 (normal) cell
lines along with antimicrobial characteristic. DPPH, MTT and Brine shrimp
lethality tests and disc diffusion method were carried out to determine the
biological activities of the different extracts of S. frigida. In addition, the
extracts which had more potent antioxidant and antiproliferative activity were
further analyzed by NMR and GC-MS. 40% methanol-water (from MeOH extract)
fraction showed higher amounts of TPC, TFC and antioxidant property. Findings of
the study for general toxicity effect showed that dichloromethane (DCM) and MeOH
extracts had weak to moderate effects. Furthermore, DCM extract indicated the
most potent anti-proliferative activity against cancer cell lines. No evidence of
antibacterial activity was determined. On the other hand, analysis of the potent
extract DCM in cytotoxic assay showed the presence of trans-phytol and cis-oleic
acid in GC-MS. Furthermore, NMR analysis of potent methanolic fractions in
antioxidant tests revealed the presence of iridoids and phenolics. Generally, the
results of TPC, TFC and antioxidant activity of extracts and fractions were in
agreement with each other.
PMID- 28496482
TI - Evaluation of the Synergistic Effect of Tomatidine with Several Antibiotics
against Standard and Clinical Isolates of Staphylococcus aureus, Enterococcus
faecalis, Pseudomonas aeruginosa and Escherichia coli.
AB - Antibiotic resistance is an important problem in antibiotic treatment of
infections, particularly in hospitals. Tomatidine is a plant secondary metabolite
with antimicrobial and antifungal effects. This study examined the possible
synergistic effect tomatidine with several antibiotics against standard and
clinical strains of Staphylococcus aureus, Enterococcus faecalis, Pseudomonas
aeruginosa and Escherichia coli. After determining the minimum inhibitory
concentrations (MICs) of antibiotics and tomatidine against the bacterial
isolates using broth microdilution method, the synergistic effect between
tomatidine and antibiotics was evaluated by checkerboard method and calculation
of FIC indices. Tomatidine alone did not show any antimicrobial effect. However,
it had synergistic effect with gentamicin and cefepime against standard and
clinical isolates of S. aureus and P. aeruginosa, respectively. It also had
synergistic effect with ampicillin and ciprofloxacin only against standard
strains of E. faecalis and P. aeruginosa, respectively. In conclusion, tomatidine
could be considered as a potential antibiotic potentiator for gentamicin,
cefepime and ciprofloxacin, and ampicillin against Staphylococcus aureus,
Pseudomonas aeruginosa, and Enterococcus faecalis infections, respectively.
However, the toxicological and pharmacological properties of tomatidine for use
as a therapeutic agent remain to be determined.
PMID- 28496483
TI - Antibacterial Activity of Isolated Immunodominant Proteins of Naja Naja (Oxiana)
Venom.
AB - The aim of this study is to investigate antibacterial effects of immunodominant
proteins isolated from the venom of Naja Naja Oxiana snake against Staphylococcus
aureus, Escherichia coli, Bacillus subtilis and Pseudomonas aeruginosa. The
innate immune system is an important line of defense against bacterial diseases.
Antibacterial peptides and proteins produced by snake venoms have recently
attracted significant attention due to their relevance to bacterial diseases and
the potential of being converted into new therapeutic agents. Identification of
immunodominant proteins of the venom of Naja Naja Oxiana snake was performed by
SDS-PAGE and western blot analysis. Identified proteins were isolated directly
from preparative gel electrophoresis by Electro-elution. In the next step,
antibacterial effects of immunodominant proteins were tested against several
strains of clinical isolates, including S.aureus, B.subtilis (Gram-positive
bacteria) P.aeruginosa and E.coli (Gram-negative bacteria) using broth
microdilution and disc-diffusion assays. In order to compare the results of the
disc-diffusion assay, antibacterial effects of several antibiotics (Gentamicin,
Ampicillin, Penicillin, Amoxicillin and Ciprofloxacin) were also examined using
the same conditions. Results showed that immunodominant proteins of (14, and
65kDa) with high immunogenicity were very effective in inhibiting the growth of
two Gram-positive bacteria (S.aureus, B.sub) that were tested. However, they were
only moderately effective in inhibiting the growth of the two tested Gram
negative bacteria (P.aeruginosa and E.coli). However, immunodominant proteins of
22 kDa and 32kDa with high immunogenicity, showed slight effectiveness in
inhibiting the growth of two; the Gram-positive and Gram-negative bacteria that
were tested. To the best of our knowledge, these immunodominant proteins are
novel antigens for potent antimicrobial effects against two gram-positive
bacteria (S.aureus, B.subtilis ) and less antimicrobial effect against two gram
negative bacteria (E.coli, P.aeruginosa) that were prepared .
PMID- 28496484
TI - In-vitro Bioactivity and Phytochemical Screening of Extracts from Rhizomes of
Eremostachys azerbaijanica rech. f. Growing in Iran.
AB - The current study evaluated the general toxicity, antioxidant, antimicrobial, and
cytotoxic activity of extracts obtained from the rhizomes of Eremostachys
azerbaijanica (Labiatae) as well as analyzed the potent extracts using GC-MS.
Extracts of E. azerbaijanica in n-hexane, dichloromethane (DCM) and methanol
(MeOH) were prepared using a Soxhlet apparatus. The antioxidant activity of the
extracts was evaluated for free radical scavenging activity by DPPH assay. The
antimicrobial activity of samples was determined by disc diffusion and brine
shrimp lethality assay (BSLA) was used to assess general toxicity. The
cytotoxicity of each extract was determined by MTT assay against human colorectal
adenocarcinoma (HT29), human lung carcinoma (A549) and a normal cell line (human
umbilical vein endothelial cells, HUVEC). The MeOH extract showed significant
antioxidant activity and the n-hexane and DCM extracts showed promising activity
against gram-positive species when compared with amikacin as a standard.
Moreover, the n-hexane extract displayed the most potent activity in general
toxicity assay. The results showed that all three extracts have cytotoxic effects
against the A549 cell line. In the case of HT29 cell lines, only the DCM extract
exhibited cytotoxicity. Interestingly, none of the extracts showed significant
cytotoxic activity against the HUVEC cell line. The bioassay-guided
identification of constituents showed the presence of fatty acids and steroids as
the compounds responsible for bioactivity in the non-polar extracts.
PMID- 28496485
TI - Phytochemicals, Antioxidant and Antiproliferative Properties of Rosmarinus
officinalis L on U937 and CaCo-2 Cells.
AB - Rosmarinus officinalis L., a medicinal herb from the labiates family, has been
reported to have potential benefit in the treatment and prevention of several
diseases. In particular its phenolics have demonstrated protective effects on
various types of cancer through several mechanisms. The present study aimed to
determine the effects of rosemary phenolic extracts on human cell functions, with
particular regard to their anti-proliferative properties in three cell types
U937, CaCo-2 and the peripheral blood mononuclear cells (PBMCs). The radical
scavenging and Ferric reducing abilities of the extracts have been assessed as
well as their cyto-toxicity and effects on cell cycle distribution and apoptosis.
About 13 compounds were identified with dominance of rosmarinic acid in the
methanolic extract and phenolic diterpens in the ethyl acetate fraction
(Carnosol, Carnosic acid and methyl Carnosate). The total polyphenolic content
was important in the first extract with 2.589 +/- 0.005 g/100 g in gallic acid
equivalent compared to 0.763 +/- 0.005 g/100 g. The methanolic fraction displayed
higher antioxidant activity (DPPHIC50: 0.510 mg/mL and FRAP: 1.714 +/- 0.068 mmol
Fe2+/g) while ethyl acetate showed pronounced antiproliferative effects (IC50:
14.85 +/- 0.20ug/mL and 14.95 +/- 2.32 ug/mL respectively for U937 and CaCo-2
cells). The anti-proliferative effect was associated with a cell cycle arrest in
S phase for U937 (62% of the population at 5 ug/mL) with a concomitant decrease
in G1 and G2/M phases. Tested extracts displayed in addition early apoptotic
effects in U937 and late apoptosis in CaCo-2 cells. The obtained data indicate
that the identified phenolics are at least partially responsible for the observed
cytotoxicity.
PMID- 28496486
TI - Chemical Composition and Antimicrobial Activities of Essential Oils of Some
Coniferous Plants Cultivated in Egypt.
AB - Family Cupressaceae is the largest coniferous plant family. Essential oils of
many species belonging to family Cupressaceae are known to have several
biological activities specially antimicrobial activity. The essential oils from
aerial parts of Calocedrus decurrens Torr., Cupressus sempervirens stricta L. and
Tetraclinis articulata (Vahl) Mast. were prepared by hydrodistillation. The
chemical composition of the essential oils has been elucidated by gas
chromatography-mass spectroscopy analysis. The prepared essential oils were
examined against selected species of Gram-positive, Gram-negative bacteria and
Candida species. Broth dilution methods were used to detect minimum inhibitory
concentration (MIC), minimum bactericidal concentration (MBC) and minimum
fungicidal concentration (MFC). Sixteen compounds were identified in the
essential oils of both Calocedrus decurrens and Cupressus sempervirens L. and
fifteen compounds were identified in the essential oil of Tetraclinis articulata.
delta-3-Carene (43.10%), (+)-Cedrol (74.03%) and Camphor (21.23%) were the major
constituents in the essential oils of Calocedrus decurrens, Cupressus
sempervirens L. and Tetraclinis articulata, respectively. The essential oils
showed strong antimicrobial activities against the selected microorganisms in
concentration range 0.02 3- 3.03 uL/mL. This study could contribute to the
chemotaxonomic characterization of family Cupressaceae. In addition, it proved
that the essential oils under investigation possess potential antimicrobial
properties.
PMID- 28496487
TI - Chemical Composition and Biological Activities of Methanolic Extract of
Scrophularia Oxysepala Boiss.
AB - Isolated five known iridoids glycosides (Scrophuloside A, Harpagoside B, 5
hydroxyloganin, 8-O-acetylharpagide and 6-O-methyl,1-glucopyranosyl catalpol),
one phenyl ethanoid glycoside (Verbascoside) and a phenyl ethanol amine (2-(4
Chlorobenzyl amino) ethanol) compound from the methanolic extract of aerial parts
of Scrophularia oxysepala using by high performance liquid chromatographyare
based on isocratic and liner gradients by C18 column. The structure elucidations
of the isolated compounds were performed by spectroscopic methods including1H
NMR, 13C-NMR, 2 D NMR technique such as HMBC( in deuterated methanol as solvent),
GC-MS and UV, also methanolic extract and fractions( fractionated on solid phase
extraction on C18 cartridge(Spack-C18)) of this plant was tested for free radical
scavenging properties toward the 1, 1-diphenyl-1-picrylhydrazyl (DPPH), general
toxicity (Brine shrimp toxicity assay) , insecticidal ( Contact toxicity
insecticidal assay) and antimalarial activities (hemebiocrystallization
inhibition assay).
PMID- 28496488
TI - Purification, Characterization and Antioxidant Activities of Enzymolysis
Polysaccharide from Grifola frondosa.
AB - Our previous study revealed that the antioxidant activity of polysaccharide
(coded as FGFP) extracted from Grifola frondosa by enzymolysis treatment was
significantly superior than that (coded as GFP) extracted by boiling-water. In
this study, one purified polysaccharide fractions (coded as FGFP-11) was obtained
from FGFP by purified using DEAE-52 column and Sephacryl S-500HR column. Results
indicated that FGFP-11 with MW of 59.82 kDa consisted of mannose, glucose and
galactose with a molar ratio of 1.00:16.36:5.25. Fourier Transform Infrared
Spectroscopy (FTIR spectrum) of FGFP-11 was similar with that of polysaccharide
extracted by boiling-water from Grifola frondosa. These indicated the enzymolysis
did not destroy the polysaccharide structure. NMR spectrum showed that FGFP-11
possess alpha-(1->6) glycosidic bond and alpha-(1->3) glycosidic bond
configuration. The experiment of Congo red also revealed that FGFP-11 had triple
helix stereo-configuration. Moreover, the antioxidant activities of FGFP-11 were
improved compared with that of GFP, especially in scavenging of hydroxyl radical
and diphenyl picryl hydrazinyl (DPPH) radical.
PMID- 28496489
TI - Homoisoflavonoids and the Antioxidant Activity of Ophiopogon japonicus Root.
AB - The root of Ophiopogon japonicus has been used as a traditional Chinese medicine
and also a functional food ingredient for a long time in China. In the present
study, 17 different homoisoflavonoid compounds were identified in the root
extract of O. japonicus by HPLC-DAD and LCMS/MS analyses. The antioxidant
activity of the of chloroform/methanol (1:1, v/v), methanol and 70% ethanol
extracts, and two major isolated homoisoflavonoid compounds
(methylophiopogonanone A and methylophiopogonanone B) from O. japonicus root were
investigated by various in-vitro assays. Methylophiopogonanone B showed the
highest antioxidant ability according to four antioxidant methods. Among the
extracts, the chloroform/methanol extract which contained high amounts of
homoisoflavonoids was found to exhibit the strongest antioxidant activity. The
results showed that O. japonicus root can be regarded as a potential source of
homoisoflavonoids and natural antioxidant.
PMID- 28496490
TI - Chitin from the Mollusc Chiton: Extraction, Characterization and Chitosan
Preparation.
AB - This study presents the first ever data of extracting chitin from the Chiton
shell, which was then converted to the soluble chitosan by soaking in the 45%
NaOH solution. The obtained chitin and chitosan were characterized by the seven
different methods. Antioxidant activity of the extracted chitosan was also
evaluated using the two methods. The shell content was divided into calcium
carbonate (90.5 %), protein (5.2%), and chitin (4.3 %). Due to the results of
element analysis and 1H NMR, the final degree of deacetylation of chitosan was
90%. Surprisingly, a significant amount of Fe was accidentally found in the shell
after demineralization, and removed from the solution through the filtering.
Nonetheless, remained Fe in the extracted chitin and chitosan was 20 times higher
than those previously reported from the shell of shrimps and crabs. Presence of
this amount of Fe could describe why the produced chitosan was darker compared to
the commercial chitosan. Antioxidant activity tests showed that the IC50 of the
extracted chitosan was higher than one estimated for the commercial chitosan.
Antioxidant activity of the extracted chitosan is even better than the commercial
version and may be used in pharmaceutical industry as a source of antioxidant.
PMID- 28496491
TI - The Effects of Transdermal Estrogen Delivery on Bone Mineral Density in
Postmenopausal Women: A Meta-analysis.
AB - Due to its minimal systematic adverse effects, transdermal estrogen is widely
used for the prevention of osteoporosis in postmenopausal women. The present meta
analysis aimed to clarify the effects of transdermal estrogen on bone mineral
density (BMD) of postmenopausal women. Studies were identified by searching
electronic databases including Cochrane Library, MEDLINE, Embase , and CINAHL
databases, and also the Sciences Citation Index. Systematic review of articles
was published between January 1989 to February 2016.Reference lists of the
included articles were also evaluated and consultations were made with relevant
experts. While 132 studies included the desired keywords, only nine clinical
trials met the inclusion criteria and were finally reviewed. The pooled percent
change in BMD was statistically significant in favor of transdermal estrogen.
According to resulting pooled estimate, lumbar spine BMD one and two years after
transdermal estrogen therapy was respectively 3.4% (95% CI: 1.7-5.1) and 3.7%
(95% CI: 1.7-5.7) higher than the baseline values. The test for heterogeneity was
not statistically significant based on the I2 heterogeneity index. One-two years
of transdermal estrogen delivery can effectively increase BMD and protect the
bone structure in postmenopausal women.
PMID- 28496493
TI - Relationship Between the Provision of Injection Services in Ambulatory Physician
Offices and Prescribing Injectable Medicines.
AB - Overuse of injections is a common problem in many low-income and middle income
countries. While cultural factors and attitudes of both physicians and patients
are important factors, physicians> financial intensives may play an important
role in overprescribing of injections. This study was designed to assess the
effects of providing injection- services in physicians> ambulatory offices on
prescribing injectable medicines. This cross-sectional study was conducted in
Tehran in 2012 -2013and included a random sample of general physicians,
pediatricians and infectious disease specialists. We collected data on the
provision of injection services in or in proximity of physician offices, and
obtained data from physicians> prescriptions in the previous three-month period.
We analyzed the data using ANOVA, Student>s t-test and linear regression methods.
We obtained complete data from 465 of 600 sampled physicians. Overall 41.9% of
prescriptions contained injectable medicines. 75% of physicians offered injection
services in their offices. Male physicians and general physicians were more
likely to offer the services, and more likely to prescribe injectables. We
observed a clear linear relationship between the injection service working hours
and the proportion of prescriptions containing injectables (p-value<0.001).
Providing injection service in the office was directly linked with the proportion
of prescriptions containing injectables. While provision of injection services
may provide a direct financial benefit to physicians, it is unlikely to be able
to substantially reduce injectable medicines> prescription without addressing the
issue.
PMID- 28496492
TI - Infective endocarditis; report from a main referral teaching hospital in Iran.
AB - BACKGROUND/OBJECTIVE: The aim of the present preliminary study was to assess the
demographic, clinical, paraclinical, microbiological, echocardiographic, and
therapeutic profile as well as in-hospital outcome of patients with infective
endocarditis at a referral center for various infectious diseases in Iran.
METHODS: Required demographic, clinical, plausible complications and paraclinical
data were collected from patients' medical charts. Echocardiographic findings
were obtained by performing transthoracic and/or transesophageal echocardiography
as clinically indicated. In addition, details of management modalities and in
hospital outcome of patients were recorded. RESULTS: During a 3-year period, 55
patients with definite or possible diagnosis of Infective endocarditis were
admitted to the ward. Twenty one (38.2%) patients were injection drug users.
Staphylococcus aureus and S.epidermidis were the most commonly isolated
microorganisms. Management modalities of Infective endocarditis included
antimicrobial therapy alone (48 cases) and the combination of antimicrobial
therapy and surgery (7 cases). CONCLUSION: The rate of negative blood culture in
our cohort is high. S. aureus and S.epidermidis were the most commonly isolated
microorganisms from positive blood cultures. Congestive heart failure was the
most frequent infective endocarditis complication as well as indication for
surgery. In-hospital mortality rate of patients was unexpectedly low.
PMID- 28496494
TI - Effect of Inhalation of Lavender Essential Oil on Vital Signs in Open Heart
Surgery ICU.
AB - This study evaluated the effects of inhalation of Lavender essential oil on vital
signs in open heart surgery ICU. The main complaint of patients after open-heart
surgery is dysrhythmia, tachycardia, and hypertension due to stress and pain. Due
to the side effects of chemical drugs, such as opioids, use of non-invasive
methods such as aromatherapy for relieving stress and pain parallel to chemical
agents could be an important way to decrease the dose and side effects of
analgesics. In a multicenter, single-blind trial, 40 patients who had open-heart
surgery were recruited. Inclusion criteria were full consciousness, lack of
hemorrhage, heart rate >60 beats/min, systolic blood pressure > 100 mmHg, and
diastolic blood pressure > 60 mmHg, not using beta blockers in the operating room
or ICU, no history of addiction to opioids or use of analgesics in regular,
spontaneous breathing ability and not receiving synthetic opioids within 2 h
before extubation. Ten minutes after extubation, the patients> vital signs
[including BP, HR, Central Venous Pressure (CVP), SPO2, and RR] were measured.
Then, a cotton swab, which was impregnated with 2 drops of Lavender essential oil
2%, was placed in patients' oxygen mask and patients breathed for 10 min. Thirty
minutes after aromatherapy, the vital signs were measured again. Main objective
of this study was the change in vital sign before and after aromatherapy.
Statistical significance was accepted for P < 0.05. There was a significant
difference in systolic blood pressure (p > 0.001), diastolic blood pressure (p =
0.001), and heart rate (p = 0.03) before and after the intervention using paired
t-test. Although, the results did not show any significant difference in
respiratory rate (p = 0.1), SpO2 (p = 0.5) and CVP (p = 0.2) before and after
inhaling Lavender essential oil. Therefore, the aromatherapy could effectively
reduce blood pressure and heart rate in patients admitted to the open heart
surgery ICU and can be used as an independent nursing intervention in stabilizing
mentioned vital signs. The limitations of our study were sample size and lack of
control group. Randomized clinical trials with larger sample size are
recommended.
PMID- 28496495
TI - Cortical Alpha Activity in Schizoaffective Patients.
AB - Objective: Electrophysiological studies have identified abnormal oscillatory
activities in the cerebral cortex in schizophrenia and mood disorders. Biological
and pathophysiological evidence suggests specific deficits in serotonin (5-HT)
receptor function in schizoaffective disorder (SA), a clinical syndrome with
characteristics of both schizophrenia and bipolar disorder. This study
investigated alpha oscillations in patients with SA. Method:
Electroencephalography was used to measure ongoing and evoked alpha oscillations
in 38 adults meeting Diagnostic and Statistical Manual of Mental Disorders-Fourth
Edition (DSM-IV) criteria for SA, and in 39 healthy controls. Results:
Spontaneous alpha power of the participants with SA was significantly lower than
that of healthy participants [F (1, 75) = 8.81, P < 0.01]. Evoked alpha activity
was also decreased in SA compared to controls [F (1, 75) = 5.67, P = 0.025].
Conclusion: A strong reduction of alpha power in the posterior regions may
reflect abnormality in the thalamocortical circuits. It is shown that hypoxia and
reduced cerebral blood flow is associated with reduced alpha activity among
different regions of the brain. Therefore, it can be concluded that greatly
decreased alpha activity, particularly in centro-parietal and occipital regions,
is related to SA symptoms such as hallucinations.
PMID- 28496496
TI - Environmental Enrichment Prevents Methamphetamine-Induced Spatial Memory Deficits
and Obsessive-Compulsive Behavior in Rats.
AB - Objective: This study was designed to examine the effect of environmental
enrichment during methamphetamine (METH) dependency and withdrawal on
methamphetamine-induced spatial learning and memory deficits and obsessive
compulsive behavior. Method: Adult male Wistar rats (200 +/- 10 g) chronically
received bi-daily doses of METH (2 mg/kg, sc, with 12 hours intervals) for 14
days. Rats reared in standard (SE) or enriched environment (EE) during the
development of dependence on METH and withdrawal. Then, they were tested for
spatial learning and memory (the water maze), and obsessive-compulsive behavior
as grooming behavior in METH-withdrawn rats. Results: The results revealed that
the Sal/EE and METH/EE rats reared in EE spent more time in the target zone on
the water maze and displayed significantly increased proximity to the platform
compared to their control groups. METH withdrawn rats reared in EE displayed less
grooming behavior than METH/SE group. Conclusion: Our findings revealed EE
ameliorates METH-induced spatial memory deficits and obsessive-compulsive
behavior in rats.
PMID- 28496497
TI - Investigation of Content and Face Validity and Reliability of Sociocultural
Attitude towards Appearance Questionnaire-3 (SATAQ-3) among Female Adolescents.
AB - Objective: This study aimed to determine the psychometric properties of
sociocultural attitude towards appearance questionnaire in female adolescents.
Method: This was a methodological study. The English version of the questionnaire
was translated into Persian, using forward-backward method. Then the face
validity, content validity and reliability were checked. To ensure face validity,
the questionnaire was given to 25 female adolescents, a psychologist and three
nurses, who were required to evaluate the items with respect to problems,
ambiguity, relativity, proper terms and grammar, and understandability. For
content validity, 15 experts in psychology and nursing, who met the inclusion
criteria, were required. They were asked to assess the qualitative of content
validity. To determine the quantitative content validity, content validity index
and content validity ratio were calculated. At the end, internal consistency of
the items was assessed, using Cronbach's alpha method. Results: According to the
expert judgments, content validity ratio was 0.81 and content validity index was
0.91. Besides, the reliability of the questionnaire was confirmed with Cronbach's
alpha = 0.91, and physical and developmental areas showed the highest reliability
indices. Conclusion: The aforementioned questionnaire could be used in researches
to assess female adolescents' self-concept. This can be a stepping-stone towards
identification of problems and improvement of adolescents' body image.
PMID- 28496498
TI - Effectiveness of Psychoeducational Group Training on Quality of Life and
Recurrence of Patients with Bipolar Disorder.
AB - Objective: Bipolar disorder (BD) is a disabling psychiatric disorder with
frequent recurrences. Besides pharmacotherapy, psychoeducation could be helpful
in reducing symptoms as well as recurrence of this disorder, leading to
improvement of patients' quality of life. This study aimed at investigating the
effectiveness of a culturally adjusted structured program for training Iranian BD
patients. Method: In a 6-month course (spring and summer 2014), 24 BD patients,
visiting the outpatient clinic of Ibn-Sina Hospital in Mashhad and experiencing
euthymic phase, were allocated in to 2 groups of intervention and control. The
intervention group received 8 sessions of psychoeducation in four weeks. Patients
in the control group received the usual treatment. The patients were evaluated
with Hamilton Depression Rating Scale, Young Mania Rating Scale, and Short Form
36 before the intervention and 4 weeks later, and the results were compared using
independent t test. The patients were reexamined after 6 months for recurrence,
hospitalization, treatment adherence, and visiting a psychiatrist, and were
compared with patients in the control groups. Results: There was a significant
difference in the intervention group in improvement in quality of life before and
after treatment (p<0.003). In addition, the difference was significant between
the 2 groups in the number of recurrence (p<0.001) and hospitalization (p<0.000)
in 6 months. Conclusion: In addition to pharmacotherapy, psychoeducation of
patients with BD can improve their quality of life and decrease the risk of
disorder recurrence.
PMID- 28496500
TI - Transition of Mental Health to a More Responsible Service in Iran.
AB - Objective: This study proposed a model for provision of an effective universal
coverage for mental health services based on global and national experiences,
available resources and the nature of primary health care system of Iran to
reduce the burden of mental health conditions. Method: A framework with
prioritized mental and social health services was devised through a review of
literature and policy documents. It was then adapted using inputs from the
stakeholders and experts. Results: The new model included 2 basic and specialized
service strata: a PHC-based infrastructure and essential requirements needed to
establish the service. Our proposed socio-mental health approach is based on a
WHO recommendation. Conclusion: The key features of the model, which is going to
be tested in a pilot study in 2015, are setting up a system for organized
referrals to specialized mental facilities and compatibility with the existing
primary health care system. Moreover, to achieve this goal, socio-mental health
technicians should be employed.
PMID- 28496499
TI - Psychiatric Comorbidities and Environmental Triggers in Patients with Chronic
Daily Headache: A Lifestyle Study.
AB - Objective: Patients with chronic daily headache (CDH) suffer from several
significant psychiatric comorbidities and have unhealthy lifestyle. We aimed at
studying psychiatric comorbidities, environmental triggers, lifestyle factors,
and intensity of CDH in patients referred by the department of neurology from
2011 to 2014. Method: Through medical and psychiatric interviews and using 0 to
10 visual analogue scale (VAS), we assessed patients with CDH, using a checklist,
to elicit psychiatric comorbidities, intensity of CDH, environmental factors, and
lifestyle derangement. Results: We interviewed 413 (age 16-80 years, mean 40 +/-
14.0) out of 548 patients; 312 (75.5%) were married, and 282 (68.1%) were female.
Environmental triggers (374, 90.6%) were the most common cause of CDH, while 214
(51.8%) had no compliance to recommended nutrition. Exercise avoidance (201,
48.7%) was the less prevalent lifestyle factor. Of the patients, 372 (90.1%) were
stressed and 162 (39.2%) had obsessive-compulsive disorder (OCD), which were the
most and less prevalent psychiatric comorbidities, respectively. Intensity of
pain was moderate to severe (mean score = 7.1+/- 1.9), while females reported
higher VAS scores (p<0.02). Patients with previous history of psychotherapy
reported higher score of VAS (p<0.001). Those patients living with a person
suffering from head pain reported more VAS score (p<0.003). Conclusion: Notable
psychiatric comorbidities were found in patients with CDH, many of which are
modifiable such as environmental triggers and unhealthy lifestyle. In heavily
populated cities, these factors may double the burden of the CDH by precipitating
new or exacerbating previous psychiatric comorbidities. We, thus, suggest
conducting more studies on this subject.
PMID- 28496501
TI - Evaluation of Knowledge and Attitude of Parents of Attention
Deficit/Hyperactivity Disorder Children towards Attention Deficit/Hyperactivity
Disorder in Clinical Samples.
AB - Objective: Knowledge and attitude of parents about attention
deficit/hyperactivity disorder (ADHD) is an important factor in management of the
disorder in children. This study investigates the parents' knowledge and attitude
towards ADHD, its symptoms, diagnosis, treatment and prognosis. Method: In this
cross-sectional descriptive study, the subjects were 150 parents (120 mother and
30 father) of ADHD children who were referred to a child psychiatry clinic
affiliated in university of social welfare and rehabilitation sciences in Tehran.
The diagnosis was made by a child psychiatrist according to DSM-IV TR criteria.
The parents completed a 40 items questionnaire that was prepared by the authors
and assessed their knowledge and attitude towards ADHD and source of their
information. Results: The most common source of parent's information about ADHD
was TV. The parent's knowledge about the symptoms of the disorder was relatively
good. But in regard to diagnosis, treatment and prognosis of the disorder, they
have very low knowledge and even incorrect beliefs. The parent's knowledge
significantly correlated with their educational level (p=0.01). Conclusion: In
general, knowledge of the parents was low and it can lead to misdiagnosis or
mismanagement of this common and important disorder and need to further
consideration in terms of educating parents about the disorder in media specially
TV.
PMID- 28496502
TI - The Effect of Creative Tasks on Electrocardiogram: Using Linear and Nonlinear
Features in Combination with Classification Approaches.
AB - Objective: Interest in the subject of creativity and its impacts on human life is
growing extensively. However, only a few surveys pay attention to the relation
between creativity and physiological changes. This paper presents a novel
approach to distinguish between creativity states from electrocardiogram signals.
Nineteen linear and nonlinear features of the cardiac signal were extracted to
detect creativity states. Method: ECG signals of 52 participants were recorded
while doing three tasks of Torrance Tests of Creative Thinking (TTCT/ figural B).
To remove artifacts, notch filter 50 Hz and Chebyshev II were applied. According
to TTCT scores, participants were categorized into the high and low creativity
groups: Participants with scores higher than 70 were assigned into the high
creativity group and those with scores less than 30 were considered as low
creativity group. Some linear and nonlinear features were extracted from the
ECGs. Then, Support Vector Machine (SVM) and Adaptive Neuro-Fuzzy Inference
System (ANFIS) were used to classify the groups. Results: Applying the Wilcoxon
test, significant differences were observed between rest and each three tasks of
creativity. However, better discrimination was performed between rest and the
first task. In addition, there were no statistical differences between the second
and third task of the test. The results indicated that the SVM effectively
detects all the three tasks from the rest, particularly the task 1 and reached
the maximum accuracy of 99.63% in the linear analysis. In addition, the high
creative group was separated from the low creative group with the accuracy of
98.41%. Conclusion: the combination of SVM classifier with linear features can be
useful to show the relation between creativity and physiological changes.
PMID- 28496503
TI - Sexual Therapy for Women with Multiple Sclerosis and Its Impact on Quality of
Life.
AB - Objective: Multiple Sclerosis (MS) is a disease with a detrimental effect on
functional status. The present study investigated the effect of a sexual therapy
program on the quality of life (QOL) of women with multiple sclerosis. Method:
Women with multiple sclerosis and sexual dysfunction (n = 30) were selected, and
were randomly assigned into the treatment (n = 15), or the control groups (n =
15). Participants of the treatment group (n = 15) received 12 weekly sessions of
sexual therapy. Participants in both groups completed the Female Sexual Function
Inventory (FSFI) and the MS Quality of Life- 54 (MSQOL-54) in the onset of the
program and at the end of the program. Results: ANCOVA(s) using pre-test scores
as covariate(s) revealed that in comparison to the control condition, MS patients
within the treatment group showed a significant improvement in their sexual
desire (0.0001), arousal (0.022), lubrication (0.001), orgasm (0.001),
satisfaction (0.0001), overall quality of life (0.001), energy (0.023), cognitive
function (0.005), and social function (0.001) at the end of the program. In
addition, they were less limited in their roles due to the emotional and health
problems. Conclusion: The present study revealed that addressing sexual
dysfunction in MS patients could improve their quality of life. In the future,
this research can extend its results, and apply the same method to men with MS to
find whether sexual therapy enhances their quality of life.
PMID- 28496504
TI - Epidemiology of Psychiatric Disorders in Iranian Children and Adolescents (IRCAP)
and Its Relationship with Social Capital, Life Style and Parents' Personality
Disorders: Study Protocol.
AB - Objective: We aimed at designing a cross sectional study to investigate the
prevalence of psychiatric disorders in Iranian children and adolescents (IRCAP)
and to determine its relationship with social capital, life style, and parents'
personality disorders. Method: This cross sectional study was a national project
implemented in all provinces of Iran. In this community-based study, using
multistage cluster sampling method, we selected 1000 children and adolescents
aged 6 to 18 years in each province. The total sample size reached to 31 000. We
randomly collected 170 blocks. Then, of each cluster head, we selected 6 cases
including 3 cases of each gender in different age groups (6- 9 years, 10- 14
years, and 15- 18 years). The clinical psychologists instructed the participants
to complete the Persian version of Kiddie-Sads-Present and Lifetime Version (K
SADS-PL). In addition, demographic data (gender, age, education, parent
education, and economic situation) and information on lifestyle, social capital,
and parents' personality disorders were obtained from the participants.
Discussion: IRCAP study presents a protocol for an epidemiological survey on the
first estimates for the prevalence of psychiatric disorders in children and
adolescents across the country. This large body of data, on a range of individual
behavioural and emotional items and scores, allows us to compare the rates and
patterns of deviance between urban and rural places of residence in 31 provinces
of Iran with non Iranian samples surveyed with the same measures.
PMID- 28496505
TI - Suicide in Iran: The Facts and the Figures from Nationwide Reports.
AB - Objective: Data on national rates of suicide is limited in Iran, preventing an
action plan for health scope of suicide prevention. The current brief study was
conducted to review available national published data on suicide and to interpret
the probable discrepancies. Method: We evaluated all 20-year recent published
original articles on committed suicides searching Iranian scientific databases,
PubMed, and Google Scholar with the keywords of suicide, mortality, and Iran.
Results: Articles showed an overall increased trend of suicidal deaths in Iran.
Discrepancies existed regarding suicide rate and demographic characteristics
among 9 English and Persian published articles. Although a suicide rate of 6.2
per 100 000 was reported in 2003, almost 31 times greater than 1991, an average
suicide rate of 9.9 per 100 000 was calculated based on data interpretations.
Conclusion: Apparently, Iran has had the highest increase in suicide-related
deaths among Eastern Mediterranean Region (EMR) and Islamic countries during the
recent decades. National policies to prevent suicide have not been efficient
enough, and urgent intervention is needed.?.
PMID- 28496506
TI - Prevalence of Hypertension in Iran 1980-2012: A Systematic Review.
AB - Background: The high prevalence of hypertension and concomitant increase in the
risk of its related disease makes it an important health concern all over the
world. Hypertension is one of the 5 global leading causes of mortality in the
world. Little is known about the current prevalence of hypertension in Iran,
however. This systematic review aimed to investigate the current prevalence of
hypertension in Iran. Methods: A systematic review of hypertension was conducted
using international databases, including Medline (PubMed) and Science Direct
(Scopus), and Persian scientific databases. The searched keywords were
"hypertension", "raised blood pressure", "prevalence", and "Iran". All original
articles in English published from 1980 to 2012 were included. After data
extraction, heterogeneity between studies and publication bias was assessed and
effect size was pooled by the random effect model. Results: Forty-two studies
with 402 282 subjects were included. The estimated prevalence of hypertension
varied all around Iran (I2 = 99%). The overall pooled prevalence of hypertension
was 22% (95%CI: 20.2 - 23.8). The prevalence of hypertension was 23.6% (95%CI:
21.1 - 26.1) in men and 23.5% (95%CI: 20.2 - 23.8) in women. In urban areas, the
prevalence of hypertension was 22.1% (95%CI: 19.4 - 24.7). Ten studies
investigated the prevalence of hypertension in rural areas and according to the
random effect model, the prevalence of hypertension in rural areas was 18.6%
(95%CI: 13.6 - 23.6). Nonsignificant publication bias was found in this review (p
value = 0.18). In our meta-regression analysis, only mean age and study quality
were associated with significant variability. Conclusion: According to this
study, hypertension is one of the most common health problems in Iran. Around one
quarter of the adult population is hypertensive and its prevalence increases by
aging. Timely and appropriate public health strategies are essential for the
improvement of the screening, treatment, and control of hypertension.
PMID- 28496508
TI - Venoplasty and Venous Stenting in Patients with Chronic Venous Insufficiency in
the Lower Extremities.
AB - Background: Venoplasty and stenting is a minimally invasive therapy that can be
used for patients with deep venous insufficiency in the lower extremities. This
study aimed at investigating the effect of venoplasty and venous stenting in
patients with chronic venous insufficiency in the lower limbs. Methods: This
prospective case-series study recruited patients with chronic deep venous
insufficiency in the lower limbs candidated for venoplasty in the Vascular Clinic
of Sina Hospital in Tehran, Iran. Venoplasty and stenting was done if the deep
venous system in the lower extremities had stenosis or obstruction on venography.
The patients were visited 1, 3, and 6 months after venoplasty to assess their
symptoms, venous clinical severity, and venous disability. Primary and secondary
patency was evaluated with Doppler ultrasound. Results: Seventy-three patients
were included in the study. The follow-up of the patients' clinical symptoms
showed significant improvement rates of about 90%, 88.7%, 92.5%, and 100% in
claudication, edema, pain, and ulcers-respectively- only 1 month after the
procedure. The stent patency rates were 93.2, 91.5, and 92.4 in the 1st, 2nd,
3rd, and 6th postprocedural months, correspondingly. The venous clinical severity
score and the venous disability score before the procedure were 14.2 and 2.73,
respectively, which were decreased to 5 and 1.1, correspondingly, at 6 months'
follow-up (p value < 0.001). Conclusion: Venoplasty and stenting in our patients
with chronic deep venous insufficiency in the lower extremities conferred a
significant improvement in clinical symptoms and a high percentage of patency.
PMID- 28496507
TI - Depression and Associated Factors in Patients with Implantable Cardioverter
Defibrillators.
AB - Background: Psychological problems such as depression constitute a dilemma that
patients with the implantable cardioverter-defibrillator (ICD) usually encounter
and may impact their quality of life. The purpose of this study was to evaluate
the prevalence of depression among adults with the ICD and the relationship
between depression and associated factors. Methods: Totally, 115 individuals with
the ICD participated in this cross-sectional study in Tehran, Iran, and
depression and other related risk factors were evaluated in them. Two
questionnaires, one for demographic characteristics and the Beck Depression
Inventory, were applied for data acquisition. The data were analyzed, and the
factors associated with depression in the patients with the ICD were assessed.
Results: The mean age of the study population was 59.85 +/- 11.46 years. Males
comprised 88 (76.5%) and females 27 (23.5%) of the patients. The multivariate
analysis on the 115 patients revealed that frequency of ICD shocks (OR = 1.08,
95%CI: 1.02 - 1.10), male sex (OR = 2.28, 95%CI: 1.027 - 5.07), more hospital
admissions (OR = 1.19, 95%CI: 1.11 - 1.25), smoking cessation (OR = 9.8, 95%CI:
4.48 - 20.07), presence of ICD shocks (OR = 4.5, 95%CI: 2.45 - 7.38),
dyslipidemia (OR = 2.8, 95%CI: 1.22 - 4.95), and family history of depression (OR
= 6.4, 95%CI: 3.0 - 13.46) were significantly and independently associated with
the Beck score classifications. Conclusion: These findings suggest that a poor
psychosocial outcome in patients with the ICD may occur as a result of a variety
of associated factors, most of which are predictable and preventable.
PMID- 28496509
TI - Effects of the Health Belief Model (HBM)-Based Educational Program on the
Nutritional Knowledge and Behaviors of CABG Patients.
AB - Background: Reducing blood pressure through diet decreases the possibility of
heart attacks, and lowering blood cholesterol can reduce the risk of coronary
artery disease. The aim of the present study was to examine the effects of
education based on the Health Belief Model on the dietary behavior of patients
following coronary artery bypass graft surgery (CABG) at the Heart Surgery
Department of Shahid Beheshti Hospital of Qom. Methods: In this semi-experimental
clinical trial, data were collected on 64 patients, at an average age of 59.9 +/-
7.26 years in the intervention group and 58.5 +/- 7.6 years in the control group.
Seventy percent of the study subjects were male and 30% were female. Intervention
and control groups were given a questionnaire, comprising 56 questions in 5
parts. The educational intervention was aimed at creating perceived
susceptibility and perceived severity in the intervention group. After 1 month.
Both groups were tested, and the resulting data were analyzed to investigate the
effects of the educational intervention on the nutritional knowledge and behavior
of the patients. Results: According to the results, educational intervention
caused a significant increase in the mean scores of knowledge (p value = 0.001),
perceived severity (p value = 0.007), and perceived benefits and barriers (p
value = 0.003) in the intervention group but did not cause a significant increase
in the mean score of nutritional behavior (p value = 0.390). Conclusion:
Education based on the Health Belief Model seems to be effective in improving
nutritional knowledge, but more consistent and comprehensive educational programs
are necessary in order to change behavior and improve nutritional behavior.
PMID- 28496511
TI - Evaluation of Coronary Arteries in Non-Ischemic Cardiomyopathies: A Case Report.
AB - Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a
congenital cardiac disease with myocardial involvement, most probably right
ventricular (RV) dysfunction, accounting for 20% of sudden cardiac deaths.
Characterized by the fibro-fatty infiltration of the RV free wall, ARVD/C
presents in adolescents with ventricular arrhythmias and heart failure symptoms
and as biventricular failure in adults. The coronary risk in these patients is
not clear. We present an incidental finding: the left anterior descending artery
cut-off in a middle-aged man with ARVD/C. He had been under treatment for heart
failure symptoms, which had decompensated frequently commencing 6 months earlier,
and therefore he was scheduled for stem cell injection. He had no chest pain or
coronary artery disease risk factors. Two-dimensional transthoracic
echocardiography demonstrated RV enlargement with moderate to severe dysfunction
and left ventricular ejection fraction (LVEF) of 35-40%, which was 45-50% two
years before. Selective coronary angiography performed 8 years previously was
normal but a new one revealed the cut-off of the left anterior descending artery
at the proximal portion, for which percutaneous coronary intervention was
performed and showed no significant lesion in the other vessels. One should
consider coronary artery disease in uncontrolled heart failure with LVEF
reduction, even in the absence of typical chest pain. It may not be the natural
course of the underlying disease.
PMID- 28496510
TI - Constrictive Pericarditis and Primary Amenorrhea with Syndactyly in an Iranian
Female: Mulibrey Nanism Syndrome.
AB - Mulibrey nanism is a rare autosomal recessive syndrome caused by a mutation in
the TRIM37 gene with severe growth retardation and multiple organ involvement.
Early diagnosis is important because 50% of the patients develop congestive heart
failure owing to constrictive pericarditis, and this condition plays a critical
role in the final prognosis. A 37-year-old female patient presented with symptoms
of dyspnea on exertion and shortness of breath. She had severe growth failure and
craniofacial dysmorphic feature. Cardiac evaluation showed constrictive
pericarditis, moderate pulmonary hypertension, and mild pericardial effusion. The
patient underwent pericardiectomy, but her thick and adhesive pericardium forced
the surgeon to do partial pericardiotomy. Our report underlines the importance of
attention to probable Mulibrey nanism when confronting patients with primary
amenorrhea, growth retardation, and dysmorphic features. Early cardiac
examination is of great significance in the course of the disorder, and patients
must be pericardiectomized to relieve the symptoms and increase survival.
PMID- 28496512
TI - Takayasu's Arteritis Presenting with Headache and Peripheral Facial Palsy: A Case
Report.
AB - Takayasu's arteritis (TA) is a rare case of granulomatous arteritis which mainly
involves the aorta and its large branches. Although arterial hypertension is the
most common feature of the disease in both adults and children, patients with TA
may present with numerous clinical manifestations. Our patient was a 45-year-old
woman, known to have hypertension from 3 years earlier following assessments made
for severe headache. One year after the diagnosis of hypertension, she developed
a left-sided lower motor neuron facial palsy, which was treated with oral
corticosteroids (Prednisolone). Notably, the patient's headache was relieved
after she took corticosteroid therapy. Transthoracic echocardiography revealed
severe aortic insufficiency and aneurysmal changes in the ascending aorta, and
she was referred to our center for further evaluation. In multi-slice computed
tomography angiography, significant long stenosis of the left subclavian artery
was seen and the diameter of the ascending aorta was 50 mm. The patient underwent
the Bentall operation. The pathologic examination of the aortic wall specimen was
compatible with giant cell aortitis and more in favor of TA with the ascending
aortic aneurysm. At 6months' follow-up, the patient was in good condition and had
almost recovered from facial palsy.
PMID- 28496513
TI - Dog Footprint in the Heart.
AB - Cardiac manifestations of the hydatid cyst are relatively uncommon. Cardiac
involvement may lead to the compression of vital organs, pulmonary hypertension,
pericardial effusion, and even anaphylaxis. A 45-year-old woman presented to the
Emergency Department of Tehran Heart Center with chest pain. Cardiac examination
revealed relatively muffled heart sounds. Echocardiography demonstrated a round
echolucent well-defined mass (47 * 25 mm) on the base and the mid lateral wall of
the left ventricle (LV) without septation. Computed tomography angiography and
cardiac magnetic resonance imaging revealed a large (52 mm) exophytic mass
originating from the lateral wall of the LV with upward growth between the left
anterior descending artery (LAD) and the left circumflex artery with no LV cavity
obliteration. Coronary angiography showed upward displacement in the LAD with
significant compressive narrowing. The patient underwent mass resection and
grafting of the LAD. During surgery after the incision of the pericardium, the
hydatid cyst entity of the mass was revealed. Hydatid cysts covered the
anterolateral surface of the LV with adhesion to the pericardium. The patient
recovered from the surgery uneventfully. Pathology report and immunological
assays confirmed the diagnosis. During a 6-month postoperative follow-up period,
she remained asymptomatic with complete recovery and no recurrence.
PMID- 28496514
TI - Anomalous Intercoronary Communication with Unidirectional Flow in the Absence of
Obstructive Coronary Artery Disease: A Case Report.
AB - Large intercoronary communications in the absence of obstructive coronary artery
disease constitute a very rare coronary artery anomaly in which there is a
readily visible connection between the 2 coronary arteries with a unidirectional
or bidirectional blood flow; consequently, this anomaly may be misinterpreted as
a functioning collateral vessel, indicative of an unrecognized proximal coronary
artery occlusion. In contrast to collateral vessels that are seen in the presence
of critical coronary artery stenosis and total occlusions, these arterial
communications are vessels that are single, extramural, straight, and large in
diameter. Myocardial ischemia could result from the coronary steal phenomenon by
a unidirectional intercoronary communication. Herein, we describe a 57-year-old
female with chest pain who was found in coronary angiography to have a single
large intercoronary channel between the posterolateral branch of the right
coronary artery and the distal left circumflex artery with a unidirectional flow.
PMID- 28496515
TI - The importance of atrial anatomy.
PMID- 28496516
TI - Effect of Corticosteroids on Pain Relief Following Root Canal Treatment: A
Systematic Review.
AB - INTRODUCTION: Post-operative pain and flare-up may occur in up to 58% of patients
following root canal treatment. The aim was to conduct a systematic review and a
possible meta-analysis to determine the effect of glucocorticosteroid (GCS) on
pain following root canal treatment. METHODS AND MATERIALS: Scopus, MEDLINE and
CENTRAL databases were searched up to 30th January 2017 with broad key words. In
addition, the reference lists in eligible papers and text books were hand
searched. Assessment of the eligibility of papers and data extraction were
performed by two independent reviewers. RESULTS: Of 9891 articles, 18 were
recruited as eligible papers. Most of these papers showed pain reducing effect of
GCS on post-endodontic pain. Because of wide heterogeneity among the recruited
papers, it was not possible to perform meta-analysis. CONCLUSION: Based on the
results of this systematic review, there is a vast heterogeneity amongst articles
regarding the use of GCS and their effect on post-operative pain after endodontic
treatment. Further investigations with similar methods and materials are needed
before meta-analysis on the effect of GCS on post-operative pain following root
canal treatment can be performed.
PMID- 28496517
TI - Root Canal Irrigants and Dentin Bonding: An Update.
AB - The purpose of the review was to assess the effect of root canal irrigants on
dentin bonding. A PubMed-based search was conducted on the articles published
from 1980 to 2016. A brief overview and reviewing the effect on dentin bonding of
common root canal irrigation solutions such as sodium hypochlorite (NaOCl),
chlorhexidine (CHX), ethylenediaminetetraacetic acid (EDTA), mixture of a
tetracycline, acid and a detergent (MTAD) and ozone was conducted. Findings
showed that, depending on the type of dentin bonding, using NaOCl may decrease,
increase or not affect the bond strength. In addition, due to its broad-spectrum
matrix metalloproteinase-inhibitory effect, CHX as well as MTAD can significantly
improve the resin-dentin bond stability. However, the effect of ozone therapy on
bond strength was controversial.
PMID- 28496518
TI - Cytotoxicity of Selected Nanoparticles on Human Dental Pulp Stem Cells.
AB - INTRODUCTION: Nanoparticles are being increasingly applied in dentistry due to
their antimicrobial and mechanical properties. This in vitro study aimed to
assess and compare the cytotoxicity of four metal oxide nanoparticles (TiO2,
SiO2, ZnO, and Al2O3) on human dental pulp stem cells. METHODS AND MATERIALS:
Four suspension with different concentrations (25, 50, 75, 100 ug/mL) of each
nanoparticle were prepared and placed into cavities of three 96-well plates
(containing 1*104 cells per well that were seeded 24 earlier). All specimens were
incubated in a humidified incubator with 5% CO2 at 37 degrees C. Mosmann's
Tetrazolium Toxicity (MTT) assay was used to determine in vitro cytotoxicity of
test materials on pulpal stem cells. Cell viability was determined at 24, 48, and
72 h after exposure. Data comparisons were performed using a general linear model
for repeated measures and Tukey's post hoc test. The level of significance was
set at 0.05. RESULTS: The tested nanoparticles showed variable levels of
cytotoxicity and were dose and time dependant. The minimum cell viability was
observed in ZnO followed by TiO2, SiO2 and Al2O3. CONCLUSION: The results
demonstrated that cell viability and morphological modifications occurred at the
concentration range of 25 to 100 ug/mL and in all nanoparticles. The higher
concentration and longer duration of exposure increased cellular death. Our
results highlight the need for a more discrete use of nanoparticles for
biomedical applications.
PMID- 28496519
TI - Letter to the Editor.
PMID- 28496520
TI - A Behavioral Process Model of Familism.
AB - Familismo, or familism, an important Latino cultural construct associated with
youth adjustment, describes the importance of family regarding support, comfort,
and services. Increased research on familism among Latino families in the past
decade has called for a theoretical process model of familism that can guide
research on familism, family processes, and youth development. In this article,
we propose the behavioral process model of familism (BPMF), which identifies
proximal mechanisms through which familism is expected to promote youth
psychological adjustment. Specifically, we propose that parenting behaviors
(e.g., monitoring, discipline strategies) are a mechanism by which parent
familism relates to youth familism and psychological adjustment both directly and
via their familism-consistent behaviors. We hypothesize direct and mediated
pathways in the BPMF and consider how sociodemographic variables modify the
described processes.
PMID- 28496521
TI - On-Chip Fluorescent Labeling using Reversed-phase Monoliths and Microchip
Electrophoretic Separations of Selected Preterm Birth Biomarkers.
AB - On-chip preconcentration, purification, and fluorescent labeling are desirable
sample preparation steps to achieve complete automation in integrated
microfluidic systems. In this work, we developed electrokinetically operated
microfluidic devices for solid-phase extraction and fluorescent labeling of
preterm birth (PTB) biomarkers. Reversed-phase monoliths based on different
acrylate monomers were photopolymerized in cyclic olefin copolymer microdevices
and studied for the selective retention and elution of a fluorescent dye and PTB
biomarkers. Octyl methacrylate-based monoliths with desirable retention and
elution characteristics were chosen and used for on-chip fluorescent labeling of
three PTB biomarkers. Purification of on-chip labeled samples was done by
selective elution of unreacted dye prior to sample. Automated and rapid on-chip
fluorescent labeling was achieved with similar efficiency to that obtained for
samples labeled off chip. Additionally, protocols for microchip electrophoresis
of several off-chip-labeled PTB biomarkers were demonstrated in poly(methyl
methacrylate) microfluidic devices. This study is an important step toward the
development of integrated on-chip labeling and separation microfluidic devices
for PTB biomarkers.
PMID- 28496522
TI - Synthesis, characterisation and Pickering emulsifier performance of poly(stearyl
methacrylate)-poly(N-2-(methacryloyloxy)ethyl pyrrolidone) diblock copolymer nano
objects via RAFT dispersion polymerisation in n-dodecane.
AB - A near-monodisperse poly(stearyl methacrylate) macromolecular chain transfer
agent (PSMA macro-CTA) was prepared via reversible addition-fragmentation chain
transfer (RAFT) solution polymerisation in toluene. This PSMA macro-CTA was then
utilised as a stabiliser block for the RAFT dispersion polymerisation of a highly
polar monomer, N-2-(methacryloyloxy)ethyl pyrrolidone (NMEP), in n-dodecane at 90
degrees C. 1H NMR studies confirmed that the rate of NMEP polymerisation was
significantly faster than that of a non-polar monomer (benzyl methacrylate, BzMA)
under the same conditions. For example, when targeting a PSMA14-PNMEP100 diblock
copolymer, more than 99% NMEP conversion was achieved within 30 min, whereas only
19% BzMA conversion was obtained on the same time scale for the corresponding
PSMA14-PBzMA100 synthesis. The resulting PSMA-PNMEP diblock copolymer chains
underwent polymerisation-induced self-assembly (PISA) during growth of the
insoluble PNMEP block to form either spherical micelles, highly anisotropic worms
or polydisperse vesicles, depending on the target DP of the PNMEP chains.
Systematic variation of this latter parameter, along with the solids content,
allowed the construction of a phase diagram which enabled pure morphologies to be
reproducibly targeted. Syntheses conducted at 10% w/w solids led to the formation
of kinetically-trapped spheres. A monotonic increase in particle diameter with
PNMEP DP was observed for such PISA syntheses, with particle diameters of up to
462 nm being obtained for PSMA14-PNMEP960. Increasing the copolymer concentration
to 15% w/w solids led to worm-like micelles, while vesicles were obtained at
27.5% w/w solids. High (>=95%) NMEP conversions were achieved in all cases and 3
: 1 chloroform/methanol GPC analysis indicated relatively high blocking
efficiencies. However, relatively broad molecular weight distributions (Mw/Mn >
1.50) were observed when targeting PNMEP DPs greater than 150. This indicates
light branching caused by the presence of a low level of dimethacrylate impurity.
Finally, PSMA14-PNMEP49 spheres were evaluated as Pickering emulsifiers.
Unexpectedly, it was found that either water-in-oil or oil-in-water Pickering
emulsions could be obtained depending on the shear rate employed for
homogenisation. Further investigation suggested that high shear rates lead to in
situ inversion of the initial hydrophobic PSMA14-PNMEP49 spheres to form
hydrophilic PNMEP49-PSMA14 spheres.
PMID- 28496523
TI - Probing the causes of thermal hysteresis using tunable Nagg micelles with linear
and brush-like thermoresponsive coronas.
AB - Self-assembled thermoresponsive polymers in aqueous solution have great potential
as smart, switchable materials for use in biomedical applications. In recent
years, attention has turned to the reversibility of these polymers' thermal
transitions, which has led to debate over what factors influence discrepancies in
the transition temperature when heating the system compared to the temperature
obtained when cooling the system, known as the thermal hysteresis. Herein, we
synthesize micelles with tunable aggregation numbers (Nagg) whose cores contain
poly(n-butyl acrylate-co-N,N-dimethylacrylamide) (p(nBA-co-DMA)) and four
different thermoresponsive corona blocks, namely poly(N-isopropylacrylamide)
(pNIPAM), poly(N,N-diethylacrylamide) (pDEAm), poly(diethylene glycol monomethyl
ether methacrylate) (pDEGMA) and poly(oligo(ethylene glycol) monomethyl ether
methacrylate) (pOEGMA). By studying their thermoresponsive behavior, we elucidate
the effects of changing numerous important characteristics both in the
thermoresponsive chain chemistry and architecture, and in the structure of their
self-assemblies. Our findings demonstrate large deviations in the reversibility
between the self-assemblies and the corresponding thermoresponsive homopolymers;
specifically we find that micelles whose corona consist of polymers with a brush
like architecture (pDEGMA and pOEGMA) exhibit irreversible phase transitions at a
critical chain density. These results lead to a deeper understanding of stimuli
responsive self-assemblies and demonstrate the potential of tunable Nagg micelles
for uncovering structure-property relationships in responsive polymer systems.
PMID- 28496524
TI - Long-term stability and reusability of molecularly imprinted polymers.
AB - Molecularly imprinted materials are man-made mimics of biological receptors.
Their polymer network has recognition sites complementary to a substrate in terms
of size, shape and chemical functionality. They have diverse applications in
various chemical, biomedical and engineering fields such as solid phase
extraction, catalysis, drug delivery, pharmaceutical purification, (bio)sensors,
water treatment, membrane separations and proteomics. The stability and
reusability of molecularly imprinted polymers (IPs) have crucial roles in
developing applications that are reliable, economic and sustainable. In the
present article the effect of crosslinkers, functional monomers and conditions
for template extraction on the long-term stability and reusability of IPs was
systematically investigated. Adsorption capacity, selectivity, morphology and
thermal decomposition of eleven different l-phenylalanine methyl ester imprinted
polymers were studied to reveal performance loss over 100 adsorption-regeneration
cycles. Furthermore, crosslinker and functional monomer specific reversible and
irreversible decomposition of imprinted polymers as a result of adsorbent
regeneration were investigated through adsorption studies, electron microscopy,
N2 adsorption and thermogravimetric analysis. A decomposition mechanism was
proposed and revealed using NMR spectroscopy. Solutions to avoid or overcome the
limitations of the most common crosslinkers, functional monomers and extraction
techniques were proposed and experimentally validated.
PMID- 28496525
TI - IL-10 and IL-10 Receptor Mutations in Very Early Onset Inflammatory Bowel
Disease.
AB - Very early onset inflammatory bowel disease (VEO-IBD) is a unique disease entity
with a complex genetic susceptibility in affected patients. Next-generation gene
sequencing techniques have revealed various monogenetic mutations contributing to
the pathogenesis of VEO-IBD, including interleukin 10 (IL-10) and IL-10 receptor
(IL-10R) mutations. In this article, we reviewed the features of and effective
therapeutic options for VEO-IBD with IL-10 and/or IL-10R mutations. The IL-10
signal pathway inhibits the release of several key cytokines and thereby has a
significant anti-inflammatory effect in the gastrointestinal tract. Mutations of
the genes encoding IL-10 and/or IL-10R have been detected in VEO-IBD patients
among myriad populations throughout the world. VEO-IBD patients with IL-10 or IL
10R mutations often present with repeated bouts of bloody diarrhea, marked weight
loss, growth retardation, and recurrent perianal problems, including abscesses,
fistulas, and significant fissures. Moreover, some patients may have folliculitis
and present with pulmonary infections. While the therapeutic efficacy of
immunosuppressants is typically poor in these patients, allogeneic hematopoietic
stem cell transplantation (HSCT) has been reported to improve symptoms
significantly. However, the long-term prognosis of VEO-IBD patients with IL-10 or
IL-10R gene mutations treated with HSCT requires further exploration to verify
the efficacy and safety of this treatment. We concluded that clinicians should
recognize the clinical phenotype of VEO-IBD, as mutational analysis of the IL-10
pathway can support the diagnosis and prompt early treatment of this complicated
disease.
PMID- 28496526
TI - Changing Trends in Age, Gender, Racial Distribution and Inpatient Burden of
Achalasia.
AB - BACKGROUND: Achalasia is an idiopathic esophageal motility disorder characterized
by dysphagia, regurgitation, chest discomfort and weight loss. The aim of this
study was to evaluate the temporal trends in demographic variables,
interventions, and inpatient burden in achalasia-related hospitalizations.
METHODS: We evaluated the National Inpatient Sample Database (NIS) for all
patients in whom achalasia (ICD-9 code: 530.0) was the principal discharge
diagnosis from 1997 to 2013. Data regarding the patient demographics, number of
hospitalizations, length of stay, associated hospital costs and temporal trends
over the study period were obtained. RESULTS: In 1997, there were 2,493
admissions with a principal discharge diagnosis of achalasia as compared to 5,195
in 2013 with an average increase of 4% per year (P < 0.001). In 1997, the
proportion of patients under 65 years of age was 53.8% versus 60.1% in 2013.
Increasing prevalence in African Americans was noted (11.1% to 17.1%). Inflation
adjusted hospital charges related to achalasia showed a mean increase of $2,521
per year (P < 0.001). There was an increase in Heller myotomy procedures over the
study period (P < 0.001). CONCLUSIONS: The number of hospitalizations for
achalasia and associated costs has significantly increased significantly over the
last 16 years in the United States with disproportionate increase in patients
under 65 years of age and racial minorities. Further research on cost-effective
evaluation and management of achalasia is required.
PMID- 28496527
TI - Correlation Between Symptom Severity and Health-Related Life Quality of a
Population With Gastroesophageal Reflux Disease.
AB - BACKGROUND: Gastroesophageal reflux disease (GERD) is a chronic disease with a
negative impact on the quality of life. The aim of this study was to investigate
the reflux symptoms and the health-related quality of life in a population with
GERD. METHODS: Data from patients with GERD, according to the Montreal
definition, were collected between January and December 2009. The enrolled
patients were classified by different reflux symptoms according to the modified
Chinese GERDQ. The general demographic data, the modified GERD impact scores and
the SF-36 questionnaire scores of these groups of patients were analyzed.
RESULTS: A total of 173 patients were enrolled, and the general data, endoscopic
findings and lifestyle habits of the participants with different severity of
heartburn or regurgitation were all similar. The patients with moderate severity
of reflux symptoms had significant lower SF-36 scores than those with mild
severity. The cases with advanced heartburn severity owned the lowest scores
among all cases. The impact on the daily activity of each affected individual had
a positive association with the stronger severity of reflux symptom. CONCLUSION:
The life quality of a population with GERD achieved the meaningful declination in
participants with the moderate severity of heartburn or regurgitation. The
severity of the reflux symptoms had a greater impact on the normal daily activity
of the patients with GERD. The cases with advanced severity of heartburn had the
worst well-being.
PMID- 28496528
TI - Long-Term Study of Children With ROME III Functional Gastrointestinal Disorders
Managed Symptomatically in a Biopsychosocial Model.
AB - BACKGROUND: Our study evaluated progression of and identified potential factors
contributing to outcomes of ROME III defined-functional gastrointestinal
disorders (FGIDs) in children treated symptomatically in a biopsychosocial model
of care with a long-term follow-up. METHODS: We performed a retrospective review
of pediatric patients who were diagnosed with ROME III defined-FGIDs including
functional abdominal pain, functional dyspepsia, irritable bowel syndrome and
abdominal migraine. Patients were managed symptomatically in a biopsychosocial
model of care from the time of initial diagnosis. Demographics, management,
progression and response to treatment assessed as complete, partial, and no
improvement were reviewed. RESULTS: Two hundred fifty-eight patients were
included with mean age of 10.6 years, female 55.4%, mean number of encounters 3.3
visits, and mean follow-up was 18.7 months (range 2 - 59, SD 15.8). Diagnoses
were functional abdominal pain 45%, irritable bowel syndrome 20.9%, multiple
13.2%, functional dyspepsia 12.8%, and abdominal migraine 8.1%. Investigations
were performed in most patients: laboratory studies in 93.4% (non-contributory
abnormal 23.6%), imaging studies in 45.3% (non-contributory abnormal 5%) and
endoscopies in 43.0% (non-contributory abnormal 1.2%). Treatment included
medication in 93.7%, and surgery in 1.9% (normal pathology). There were new
functional gastrointestinal diagnosis in 11.6%, evolution of FGIDs, from one to
another in 12.0%, and recurrence found in 35.7% of patients. There were 60.1%
patients in the complete improvement group (CIG) and 39.1% in the partial/no
improvement group (PIG/NIG). No statistical difference was found between CIG and
PIG/NIG regarding demographics or evaluation. PIG/NIG had more encounters (mean
3.63 vs. 3.11; P = 0.03), had non-contributory lab abnormalities (34.4% vs.
20.0%; P = 0.01), needed more endoscopies (52.4% vs. 36.8%; P = 0.02), required
more treatment changes (mean 1.41 vs. 0.81; P < 0.01) and developed new
functional gastrointestinal diagnoses (19.4% vs. 6.5%; P < 0.01) with long-term
follow-up. CONCLUSIONS: Patients with ROME III defined-FGIDs who experience
partial or no improvement with treatment develop new FGID diagnosis, need more
number of follow-up visits, require more number of endoscopies, need more
treatment changes, and have more non-contributory laboratory abnormalities,
compared to those who experience complete improvement. Symptomatic treatment
offered in a biopsychosocial model of care is possibly beneficial in managing
children with FGIDs.
PMID- 28496529
TI - Discontinuation of Scheduled Infliximab in Crohn's Patients With Clinical
Remission: A Retrospective Single-Center Study.
AB - BACKGROUND: It is crucial to determine whether infliximab (IFX) therapy could be
safely interrupted in Crohn's disease (CD) patients with clinical remission. The
outcome and risk predictors of relapse after IFX therapy stopped are
controversial. The aim was to assess the relapse and predictive factors after IFX
discontinuation in CD patients with clinical remission. METHODS: A retrospective
cohort of CD patients with clinical remission who discontinued scheduled IFX
therapy at Nanfang Hospital were included. The primary outcome was relapse. All
patients were followed up for more than 3 months. Demographic, clinical, and
laboratory parameters were evaluated for their predictive value of relapse.
RESULTS: After a median follow-up period of 12.2(4.8 - 21.2) months, 55.7%
(59/106) patients experienced a relapse. The cumulative relapse rate was 39%, 48%
and 61% at 6 months, 1 year and 2 years, respectively. Based on multivariable
analysis, CD-related surgery before infusion (P = 0.013, hazard ratio (HR):
2.671, 95% confidential interval (CI): 1.230 - 5.798), step-up therapeutic
regimen (P = 0.035, HR: 2.073, 95%CI: 1.054 - 4.080), low albumin (Alb) level at
week 0 (P = 0.022, HR: 3.431, 95%CI: 1.196 - 9.846) and high C-reactive protein
(CRP) level at week 30 (P = 0.007, HR: 2.643, 95%CI: 1.310 - 5.332) were
associated with clinical relapse. CONCLUSIONS: After cessation of scheduled IFX
therapy in CD patients with clinical remission, nearly half of the patients
experienced a relapse within 1 year. In the event of the presence of certain
predictive factors, IFX scheduled therapy should probably be continued.
PMID- 28496530
TI - Assessment of the Relation Between SNP in MxA Gene and the Responsiveness of
Egyptian HCV Genotype 4 Patients to Pegylated Interferon and Ribavirin Treatment.
AB - BACKGROUND: Pegylated interferon (PegIFN) is used in the treatment of chronic
hepatitis C virus (HCV) patients especially in resource limited countries.
Treatment with PegIFN stimulates the expression of a number of host genes
encoding enzymes with antiviral activities, including myxovirus resistance gene-A
(MxA gene). MxA gene was found to have a single nucleotide polymorphism (SNP) at
position -88 in the promoter region that affects the expression of MxA gene
protein and was suggested to affect the treatment outcome. The aim of the work
was to assess the relation between the SNP in the MxA gene and its impact on
treatment of chronic HCV patients with PegIFN and ribavirin. METHODS: We
therefore genotyped the biallelic G/T SNP in the promoter region of MxA gene at
position -88 from the transcription start site by restriction fragment length
polymorphism (RFLP) in 70 chronic HCV genotype 4 interferon naive Egyptians and
40 healthy controls. RESULTS: G allele was the prevalent one in both HCV patients
group (105, 74.5%) and control group (66, 82.5%), while T allele was less
expressed in patients group (36, 25.5%) and control group (14, 17.5%). There is
no correlation between genotypes and response to IFN-alpha therapy: GG (OR:
0.958, 95% CI: 0.541 - 1.698, P = 0.884), GT (OR: 0.667, 95% CI: 0.188 - 2.362, P
= 0.530), and TT (OR: 0.300, 95% CI: 0.083 - 1.090, P = 0.067). CONCLUSION: MxA
nt-88 SNP did not affect the sustained virological response (SVR) rates after
PegIFN and ribavirin combined treatment and did not act as a biological marker to
potentially identify responders and non-responders to treatment. Our results call
for additional large studies and/or meta-analysis of all currently available data
to examine the role of MxA nt-88 SNP in predicting response to PegIFN and
ribavirin in patients with IFN-alpha naive HCV genotype 4.
PMID- 28496531
TI - Differential Simultaneous Liver and Kidney Transplant Benefit Based on Severity
of Liver Damage at the Time of Transplantation.
AB - BACKGROUND: We evaluated the concept of whether liver failure patients with a
superimposed kidney injury receiving a simultaneous liver and kidney transplant
(SLKT) have similar outcomes compared to patients with liver failure without a
kidney injury receiving a liver transplantation (LT) alone. METHODS: Using data
from the United Network of Organ Sharing (UNOS) database, patients were divided
into five groups based on pre-transplant model for end-stage liver disease (MELD)
scores and categorized as not having (serum creatinine (sCr) <= 1.5 mg/dL) or
having (sCr > 1.5 mg/dL) renal dysfunction. Of 30,958 patients undergoing LT,
14,679 (47.5%) had renal dysfunction, and of those, 5,084 (16.4%) had dialysis.
RESULTS: Survival in those (liver failure with renal dysfunction) receiving SLKT
was significantly worse (P < 0.001) as compared to those with sCr < 1.5 mg/dL
(liver failure only). The highest mortality rate observed was 21% in the 36+ MELD
group with renal dysfunction with or without SLKT. In high MELD recipients (MELD
> 30) with renal dysfunction, presence of renal dysfunction affects the outcome
and SLKT does not improve survival. In low MELD recipients (16 - 20), presence of
renal dysfunction at the time of transplantation does affect post-transplant
survival, but survival is improved with SLKT. CONCLUSIONS: SLKT improved 1-year
survival only in low MELD (16 - 20) recipients but not in other groups.
Performance of SLKT should be limited to patients where a benefit in survival and
post-transplant outcomes can be demonstrated.
PMID- 28496532
TI - Lack of Association Between the Clinical Outcome of Clostridium difficile
Infection and Current Steroids Use.
AB - BACKGROUND: The purpose of this study was to compare the outcome of Clostridium
difficile infection (CDI) in patients on systemic steroids for various
indications to patients not on steroids in term of disease severity, and
associated morbidity and mortality. METHODS: We retrospectively reviewed records
of all patients with CDI at our hospital from January 2011 to December 2016.
Patients were evaluated for baseline characteristics, comorbidities, medications,
disease severity, disease-related length of stay (LOS) from the diagnosis of CDI
to discharge, need for surgical intervention, and disease-related mortality.
Based on systemic steroids use, patients who were using steroids for different
indications constituted the study population, and those with no steroids use were
clustered as a control group. RESULTS: Of the 258 patients included, males were
127 (49%). Severe and severe-complicated CDI developed in 21/63 (33.3%) and 1/63
(1.6%) of patients on steroids (average daily dose of 20 mg), and in 73/195
(37.4%) and 5/195 (2.6%) of patients with no steroids use (P = 0.56 and P = 0.66,
respectively). Surgical intervention was not required in the steroids group and
5/195 (2.7%) of patients not on steroids underwent bowel surgeries (P = 0.38).
Mean LOS (days) was 11.6 +/- 1.5 in the steroids group and 10.4 +/- 0.7 in the no
steroids group (P = 0.4). CDI-related mortality occurred in 9/63(14.3%) of
patients on steroids, and in 15/195 (7.7%) of patients not on steroids (P = 0.12;
odds ratio (OR): 2; 95% confidence interval (CI): 0.8 - 4.8). CONCLUSION: There
was no significant difference in the severity of CDI, need for surgical
interventions, disease-related LOS and mortality in systemic steroids users
compared to patients not on steroids.
PMID- 28496533
TI - The Diagnostic Value of Alarm Features for Identifying Types and Stages of Upper
Gastrointestinal Malignancies.
AB - BACKGROUND: Upper gastrointestinal (GI) malignancies are an uncommon cause of
dyspepsia but of great concern. The aim of this study was to determine the
association between alarm features and each type and stage of upper GI
malignancies. METHODS: Patients who underwent endoscopy for symptoms of dyspepsia
between January 2008 and December 2009 were retrospectively collected. Alarm
features studied in this study were dysplasia, body weight loss and GI bleeding.
Patients were classified according to the findings of endoscopy and histological
reports. RESULTS: A total of 3,926 patients were included in the study, with 82
(2.1%) cases with GI malignancies. The specificity and negative predictive value
of alarm features ranged from 93.8% to 99.8%, but the sensitivity and positive
predictive value ranged from 11.6% to 29.3%. The only variable with a positive
predictive value was dysphagia (66.7%). The patients with esophageal cancers and
upper gastric cancers had the highest ratio of alarm features, most body weight
loss and dysphagia. There was a positive correlation between alarm features and
advanced stages of gastric cancers, with the exception of GI bleeding sign.
CONCLUSION: Although alarm features had a low sensitivity in identifying patients
with upper GI malignancies, the presence of alarm features did help diagnose
esophageal or upper gastric cancer and the sign of GI bleeding for early gastric
cancer. In addition, dysphagia and weight loss are associated with higher stages
of gastric cancer.
PMID- 28496534
TI - Collagenous Gastritis in a Young Female With IgA Deficiency.
AB - Collagenous gastritis, without colonic involvement, is exceptionally rare. It is
not known to be associated with IgA deficiency and scleroderma. This is the first
report of this type of association. We present a 26-year-old white female with a
past medical history of gastroesophageal reflux disease and scleroderma. She was
evaluated for complaints of abdominal pain and diarrhea.
Esophagogastroduodenoscopy showed gastritis and duodenitis. Colonoscopy was
normal. The histopathological report showed collagenous gastritis and focal
lymphocytic duodenitis. A definitive treatment has not been established for this
condition. Reporting such cases furthers understanding of the disease and will
help to establish diagnostic criteria and to develop therapeutic strategies.
PMID- 28496535
TI - Spontaneous Rupture of a Choledochal Cyst During Post Partum: A Rare
Presentation.
AB - With the advent of newer radiological investigations, choledochal cysts are being
diagnosed more often in present era. These cysts are commonly diagnosed in early
childhood and infancy, although some go undetected to be diagnosed in adulthood.
These malformations are associated with multiple complications like cholangitis,
jaundice, pancreatitis, rupture or even malignancy. Here we describe a post
partum female, who was diagnosed to have choledochal cyst during sixth month of
pregnancy. She presented with obstructive jaundice in cholangitis and was
subjected to endoscopic retrograde cholangiopancreatography (ERCP) with stenting.
This female delivered normally at term. She again had jaundice with cholangitis
during early post partum period. Endoscopic stenting could be performed. She had
features of peritonitis after 1 week of stenting. Investigations were performed
and a diagnosis of spontaneous rupture of choledochal cyst was made. She
underwent laparotomy and lavage with complete excision of the choledochal cyst
and Roux-en-Y hepaticojejunostomy.
PMID- 28496536
TI - Percutaneous Endoscopic Gastrostomy in a Patient With Continuous Intrathecal
Baclofen Infusion Therapy.
AB - Percutaneous endoscopic gastrostomy (PEG) is the method of choice in patients
requiring long-term enteral tube feeding. In patients with intrathecal baclofen
infusion therapy (IBT) pump implantation, infection via the skin and soft tissue
may be an issue of concern. The introducer technique for gastrostomy tube
insertion may be useful in reducing the risk of peristomal infection. Although
the presence of a PEG tube has been reported as a risk factor for implantation
site infection (for newly inserted IBT pumps), whether existing IBT pumps are at
risk for infection during or after the placement of a PEG tube is not clear. We
report a case where PEG was successfully performed using the introducer technique
on a patient with an IBT pump implant.
PMID- 28496537
TI - Post-Colonoscopy Colonic Perforation Presenting With Subcutaneous Emphysema: A
Case Report.
AB - Colonoscopy is performed for both diagnostic and therapeutic indications.
Although rare, associated complications can be quite serious. The frequency of
these complications depends mainly on the skills of the physicians doing the
procedure, and the diagnostic or therapeutic indications. Major complications
include adverse anesthetic related events, aspiration pneumonia, bleeding, and
colonic perforation. We present a rare case of a post-colonoscopy perforation
presenting with subcutaneous emphysema and free mediastinal, and intra-peritoneal
air. The patient was successfully managed conservatively with complete resolution
of symptoms.
PMID- 28496538
TI - Iron Pill Gastritis: An Under Diagnosed Condition With Potentially Serious
Outcomes.
AB - Given the ubiquitous use of oral iron therapy, their side effects are often
encountered and well recognized in clinical practice. However, iron pill
gastritis remains an often under-reported and elusive diagnosis. An astute
clinician should be aware of this condition in order to promptly discontinue oral
iron and institute timely treatment. Here in, we present a case of a 46-year-old
woman who presented to the gastroenterology clinic with vague epigastric pain and
microcytic anemia. Esophagogastroduodenoscopy revealed multiple gastric erosions
and non-bleeding gastric antral ulcer with biopsies showing excessive iron
deposition suggestive of iron pill gastritis. We reviewed the clinical features,
pathology, and treatment of iron pill gastritis along with the review of the
literature.
PMID- 28496539
TI - Efficacy and Safety of Direct-Acting Oral Anticoagulants Use in Acute Portal Vein
Thrombosis Unrelated to Cirrhosis.
AB - In acute portal vein thrombosis (APVT) unrelated to cirrhosis, anticoagulant
therapy is classically started with low molecular weight heparin or vitamin K
antagonists. New direct-acting oral anticoagulants (DOACs) are used in the
treatment of venous thrombosis outside the splanchnic vascular bed, but not in
the latter. We report a young female with APVT occurring in a non-cirrhotic liver
linked to heterozygosity of factor V-Leiden and prothrombin G20210A gene
mutations. Rivaroxaban was started, with total recanalization of the left and
partial recanalization of the right portal vein branches, without complications.
New DOACs do not need daily subcutaneous injections nor routinely blood
coagulation control tests, making its use attractive, eventually increasing
patient's compliance. If proved to be safe and effective in the future studies,
its use may be extended to PVT treatment. This case shows that rivaroxaban was
safe, not only prevented the extension of thrombosis in the portal tract, but
also resolved PVT, at least partially.
PMID- 28496541
TI - Atypical Presentation of Gastric Volvulus.
AB - Gastric volvulus has been reported in all age groups; however, it is typically
diagnosed in the elderly. Organo-axial volvulus is the most common type, followed
by the mesentero-axial and the combined types. Depending on the etiology, gastric
volvulus can also be classified as primary (idiopathic) or secondary. Treatment
of acute gastric volvulus involves laparoscopic or endoscopic
procedures/maneuvers, depending on the severity of symptoms and surgical
eligibility of the patient. Chronic gastric volvulus is typically managed
conservatively, although laparoscopic or endoscopic interventions can also be
employed depending on the severity of presentation.
PMID- 28496540
TI - Recombinant Factor VIIa Use for Endoscopic Retrograde Cholangiopancreatography
With Sphincterotomy in a Patient With Choledocholithiasis and Unusual
Coagulopathy.
AB - Endoscopic retrograde cholangiopancreatography (ERCP) is a procedure that
combines the use of endoscopy and fluoroscopy to diagnose and treat
pancreaticobiliary disorders. The risks of ERCP include pancreatitis, infection,
bleeding and perforation. Bleeding during ERCP typically develops after
sphincterotomy, hence patients should be screened and tested for coagulopathy
before undergoing ERCP. Coagulopathy is a major risk factor for ERCP-related
bleeding. Inherited factor VII (FVII) deficiency is a rare autosomal recessive
hemorrhagic disorder that can lead to significant coagulopathy and severe
bleeding if not appropriately recognized and treated preoperatively. Clinically,
the disease ranges between an asymptomatic state to lethal hemorrhage and the
degree of FVII deficiency does not correlate with the severity of bleeding. The
use of FVII replacement therapy has been reported to prevent bleeding during
surgery. We present the first report of a patient with a rare cause of
coagulopathy due to inherited FVII deficiency who successfully underwent ERCP
with sphincterotomy without bleeding where we used recombinant factor VIIa before
and after the procedure.
PMID- 28496542
TI - Multiple Duodenal Lipomas as a Rare Cause of Upper Gastrointestinal Obstruction:
Case Report and Literature Review.
AB - Duodenal lipomas are rare benign tumors and pose a diagnostic challenge as their
symptoms are non-specific. In this article, we reported a case of duodenal lipoma
presenting as upper gastrointestinal obstruction and reviewed the literature on
relevant clinical manifestation, diagnosis and treatment. Our review of
literature indicated that multiple duodenal lipomas as a cause of upper
gastrointestinal obstruction as reported here are extremely rare. The
preoperative computed tomography and magnetic resonance imaging are the key to
diagnosis, and surgical resection is the most effective means for the management
of such duodenal lipomas.
PMID- 28496544
TI - Hemodynamic Effects of Sodium-Glucose Cotransporter 2 Inhibitors.
AB - It is widely accepted that obesity and type 2 diabetes mellitus (T2DM) increase
the risk of heart failure (HF) independently of underlying coronary artery
disease. The changes in myocardial structure or function associated with diabetes
have been termed diabetic cardiomyopathy. Corresponding to changes in the risk
factors for HF, an epidemiologic transition is underway from HF with a reduced
ejection fraction to HF with a preserved ejection fraction. Hyperglycemia can
damage the myocardium, even before diagnosis of diabetes, but intensive glycemic
control has no impact on the risk of HF in patients with T2DM. Recent clinical
studies have demonstrated that sodium-glucose cotransporter 2 (SGLT2) inhibitors,
which inhibit renal reabsorption of glucose, decrease the risk of HF in T2DM
patients. The cardioprotective mechanisms involved appear to be multifactorial
and have been the subject of considerable debate. This review focuses on the
hemodynamic effects of SGLT2 inhibitors in T2DM patients and the mechanisms by
which these drugs decrease the risk of HF.
PMID- 28496543
TI - Combination Antifungal Therapy: A Review of Current Data.
AB - The incidence of invasive fungal infections has been on the rise, particularly in
transplant recipients and in patients with hematological malignancies and other
forms of immunosuppression. There is a mismatch between the rate of antifungal
resistance and the development of new antifungal agents. Based on this, the idea
of combining antifungals in the treatment of invasive fungal infections appears
tempting for many clinicians, particularly after many in vitro studies showed
synergism between many antifungal agents. Several randomized controlled trials
have been published regarding the efficacy and safety of combination of
antifungals, but the high cost, the limited number of cases and the multitude of
confounding factors lead in some instances to weak and sometimes contradictory
results. The lack of consensus in many clinical scenarios raises the importance
of the need for more studies about combination antifungal therapies and should
incite infectious disease societies to develop specific recommendations for the
clinicians to follow while approaching patients with invasive fungal infections.
PMID- 28496545
TI - C-Reactive Protein and Frailty in the Elderly: A Literature Review.
AB - Chronic inflammation is a well-established background process in many age-related
diseases. Many recent studies investigate the use of various inflammatory
biomarkers such as C-reactive protein (CRP), interleukin-6, and interleukin-1 as
predictors of physical and cognitive performance among elders. The phenotype of
frailty has also been associated with underlying inflammatory mechanisms. The aim
of this article was to review the literature referring to the correlation of CRP
serum levels and frailty in older individuals. We tried to identify all relevant
publications regarding the relation of CRP as an index of frailty in the elderly
and its potential use. Although many studies in the recent medical literature
positively associate serum CRP levels and frailty in older individuals, some do
not, and some raise some interesting questions and set the basis for future
studies. The association of CRP and frailty in elder patients should be
considered when clinicians interpret inflammatory biomarkers in various clinical
settings in such patients. Well-designed, prospective clinical trials are
warranted to better assess the role and pathophysiology of frailty in the elderly
and its mechanisms as also the exact role of CRP as an inflammatory marker and as
a prognostic index in this syndrome.
PMID- 28496546
TI - The Epidemiology and Risk Factors for Postoperative Pneumonia.
AB - Postoperative pneumonia is a common complication of surgery, and is associated
with marked morbidity and mortality. Despite advances in surgical and anesthetic
technique, it persists as a frequent postoperative complication. Many studies
have aimed to assess its burden, as well as associated risk factors. However,
this complication varies among the different surgical specialties, and there is a
paucity of reports that comprehensively evaluate this complication. Therefore,
the purpose of this study was to review the epidemiology and risk factors of
postoperative pneumonia in the setting of: 1) general surgery; 2) cardiothoracic
surgery; 3) orthopedic and spine surgery; and 4) head and neck surgery.
PMID- 28496547
TI - Effect of Ezetimibe Monotherapy on Low-Density Lipoprotein Cholesterol and on
Markers of Cholesterol Synthesis and Absorption in Japanese Patients With
Hypercholesterolemia.
AB - BACKGROUND: The aim of this study was to evaluate effect of ezetimibe monotherapy
on serum low-density lipoprotein cholesterol (LDL-C) in Japanese patients and to
investigate the association between changes of LDL-C and changes of markers for
cholesterol synthesis and absorption. METHODS: Seventy-six hypercholesterolemic
patients without statin therapy were enrolled and randomized to two groups, which
were an ezetimibe group (group E, n = 44) and a control group without ezetimibe
treatment that received diet therapy alone (group C, n = 32). The study period
was 12 weeks. In group E, 10 mg of ezetimibe was administered daily after
breakfast. Serum lipids were measured every 4 weeks, while lathosterol (a
cholesterol synthesis marker) and campesterol and sitosterol (cholesterol
absorption markers) were examined at baseline and at 12 weeks. RESULTS: A
significant reduction of LDL-C was observed in group E at both 4 and 12 weeks
(from 155 +/- 3.9 to 128 +/- 3.4 mg/dL and 132 +/- 3.9 mg/dL, respectively, both
P < 0.01), associated with an increase of high-density lipoprotein cholesterol
(HDL-C)at 12 weeks (from 53 +/- 1.3 to 55 +/- 1.5 mg/dL, P < 0.05) and no change
of triglycerides. In contrast, none of these lipids changed in group C. An
increase of lathosterol and a decrease of campesterol and sitosterol were
observed in group E, while none of these markers changed in group C. When group E
was divided into two subgroups according to the reduction of LDL-C, which were a
good response group (reduction >= 20 mg/dL, DeltaLDL-C = -27.9 +/- 1.3 mg/dL, n =
18) and a poor response group (reduction < 20 mg/dL, DeltaLDL-C = -3.7 +/- 2.5
mg/dL, n = 26), baseline levels of campesterol and sitosterol were higher in the
good response group. CONCLUSION: Ezetimibe monotherapy reduced LDL-C and
increased HDL-C, with the reduction of LDL-C being greater in patients with
higher levels of cholesterol absorption markers.
PMID- 28496548
TI - Palliative Thoracic Radiotherapy for Lung Cancer: What Is the Impact of Total
Radiation Dose on Survival?
AB - BACKGROUND: Effective symptom palliation can be achieved with low-dose palliative
thoracic radiotherapy. In several studies, median survival was not improved with
higher doses of radiation. More controversy exists regarding the impact of higher
doses on 1- and 2-year survival rates. Therefore, a comparison of survival
outcomes after radiotherapy with different biologically equivalent doses
(equivalent dose in 2-Gy fractions, EQD2) was performed. METHODS: This was a
retrospective single-institution study of 232 patients with small or non-small
cell lung cancer. Most commonly 2 fractions of 8.5 Gy were prescribed (34%),
followed by 10 fractions of 3 Gy or equivalent regimens (30%, EQD2 circa 33 Gy).
The highest EQD2 consisted of 45 Gy. Intention-to-treat analyses were performed.
RESULTS: Survival was significantly shorter with regimens of intended EQD2 < 33
Gy, e.g., 2 fractions of 8.5 Gy (median 2.5 months compared to 5.0 and 7.5 months
with EQD2 of circa 33 and 45 Gy, respectively). The 2-year survival rates were
0%, 7% and 11%, respectively. In 128 prognostically favorable patients, median
survival was comparable for the three different dose levels (6 - 8.3 months). The
2-year survival rates were 0%, 10%, and 13%, respectively (not statistically
significant). CONCLUSION: Although most of the observed survival differences
diminished after exclusion of poor prognosis patients with reduced performance
status and/or progressive extrathoracic disease, a slight increase in 2-year
survival rates with higher EQD2 cannot be excluded. Because of relatively small
improvements, a confirmatory randomized trial in this subgroup would have to
include a large number of patients.
PMID- 28496549
TI - Phosphodiesterase-5 Inhibitors Improve Clinical Outcomes, Exercise Capacity and
Pulmonary Hemodynamics in Patients With Heart Failure With Reduced Left
Ventricular Ejection Fraction: A Meta-Analysis.
AB - BACKGROUND: Several studies have compared the use of phosphodiesterase-5 (PDE5)
inhibitors sildenafil or udenafil with the placebo in patients suffering from
pulmonary hypertension (PH) due to left chronic heart failure (CHF),
corresponding to group 2 (PH due to left heart disease) of the PH classification
(according to 2015 ESC/ERS guidelines for the diagnosis and treatment of PH). The
results of the use of PDE5 inhibitors in the PH due to left heart disease were
inconsistent and heterogeneous. Therefore, we carried out a meta-analysis to
assess the effect of PDE5 inhibitors in this clinical setting, i.e., patients
with left CHF. METHODS: A systematic search was conducted using the PubMed and
Embase electronic archives. Studies had to be prospective randomized controlled
trials (RCTs). In each of the RCTs admitted to meta-analysis, a comparison was
made between a group of CHF patients taking a PDE5 inhibitor and a second group
assigned a placebo. Studies were incorporated in the meta-analysis provided that
they had sufficient information about two or more of the following clinical,
ergospirometric or hemodynamic outcomes: the composite of all-cause death and
hospitalization, adverse events, peak VO2, 6-min walking distance (6MWD), left
ventricular ejection fraction (LVEF), E/e' ratio, mean pulmonary arterial
pressure (mPAP), pulmonary arterial systolic pressure (PASP), and pulmonary
vascular resistance (PVR). RESULTS: Fourteen studies enrolling a total of 928
patients were incorporated in the meta-analysis. Among them,13 were RCTs and one
was a subgroup analysis. Among patients with CHF with reduced left ventricular
ejection fraction (HFREF, n = 555), a significant benefit was conferred by PDE5
inhibitors against the risk of the composite endpoint of death and
hospitalizations (odds ratio (OR): 0.28; 95% confidence interval (CI): 0.10 -
0.74; P = 0.03). Furthermore, among HFREF patients, PDE5 inhibitors were
associated with a significant improvement in peak VO2 (difference in means (MD):
3.76 mL/min/kg; 95% CI: 3.27 - 4.25) as well as in 6MWD (MD: 22.7 m; 95% CI: 8.19
- 37.21) and LVEF (MD: 4.30%; 95% CI: 2.18% to 6.42%). For patients with HFREF,
PDE5 inhibitors caused a non-significant reduction in mPAP, while PASP was
significantly reduced (MD: -11.52 mm Hg; 95% CI: -15.56 to -7.49; P < 0.001). By
contrast, in the RCTs of patients with CHF with preserved left ventricular
ejection fraction (HFpEF, n = 373), no benefit ensued from PDE5 inhibitor use
regarding all of the investigated clinical, ergospirometric or hemodynamic
endpoints. CONCLUSIONS: PDE5 inhibitors improved clinical outcomes, exercise
capacity and pulmonary hemodynamics in patients with HFREF, but not in HFpEF.
However, considering the relatively small size of the HFpEF subset enrolled so
far in the RCTs that explored the PDE5 inhibitor effects, further research in
this field is undoubtedly warranted.
PMID- 28496550
TI - Efficacy and Safety of SGLT2 Inhibitors in Reducing Glycated Hemoglobin and
Weight in Emirati Patients With Type 2 Diabetes.
AB - BACKGROUND: SGLT2 inhibitors are a new class of drugs that act by inhibiting
glucose reabsorption in the proximal renal tubules. Many trials have demonstrated
their effectiveness in reducing glycated hemoglobin (HbA1c) and weight, but they
have never been examined in Arab or Emirati populations. METHODS: We assessed the
efficacy of SGLT2 inhibitors in reducing HbA1c and weight in our population and
specifically in an Emirati cohort. We also assessed the effect on fasting blood
glucose, blood pressure, lipid profile, serum creatinine, and side effects.
RESULTS: The total number of patients was 307. The baseline HbA1c in the Emirati
cohort was 8.9+/-1.7%, which dropped significantly to 8+/-1.5% at 6 months (P =
0.0001). At 1 year, the mean HbA1c was 8+/-1.4%, which was significantly
different from baseline (P = 0.0001). However, the change in mean HbA1c from 6
months (8+/-1.5%) to 1 year (8+/-1.4%) was not statistically significant (P =
0.88). A similar highly significant change was observed when comparing weights at
baseline and 6 months in the Emirati population (85.7 +/- 17.8 kg vs. 84 +/- 17.2
kg, P = 0.0001). Total cholesterol dropped significantly at 6 months (P = 0.008),
as did low-density lipoprotein (LDL) (P = 0.005). CONCLUSIONS: The use of SGLT2
inhibitors is associated with significant reductions in HbA1c and weight. Unlike
all previous trials, the inhibitors significantly reduced total cholesterol and
LDL. Larger trials are needed to reassess their effects on lipid parameters.
PMID- 28496551
TI - Lack of Association Between Toxoplasma gondii Infection and Diabetes Mellitus: A
Matched Case-Control Study in a Mexican Population.
AB - BACKGROUND: Very little is known about the association between infection with
Toxoplasma gondii (T. gondii) and diabetes mellitus. We perform an age- and
gender-matched case-control study to determine the association of T. gondii
infection and diabetes mellitus. METHODS: Cases included 156 patients with
diabetes mellitus and 156 controls without diabetes mellitus who attended in two
public clinics in Durango City, Mexico. Sera of cases and controls were tested
for the presence of anti-Toxoplasma IgG and IgM antibodies using commercially
available enzyme-linked fluorescence assays (ELFA). RESULTS: Anti-T. gondii IgG
antibodies were found in 10 (6.4%) of the 156 cases and in five (3.2%) of the 156
controls (odds ratio (OR): 2.06; 95% confidence interval (CI): 0.69 - 6.19; P =
0.18). The frequency of high (> 150 IU/mL) anti-T. gondii IgG levels in
seropositive cases (1/10: 10.0%) was comparable to the one (1/5: 20%) in
seropositive controls (OR: 0.44; 95% CI: 0.02 - 9.03; P = 1.00). None of the 10
cases and five controls with seropositivity to anti-T. gondii IgG antibodies were
positive for anti-T. gondii IgM antibodies. Stratification by gender showed
similar frequencies of T. gondii infection in female cases (7/107: 6.5%) and
female controls (4/107: 3.7%) (OR: 1.80; 95% CI: 0.51 - 6.34; P = 0.53), and in
male cases (3/49: 6.1%) and male controls (1/49: 2.0%) (OR: 3.13; 95% CI: 0.31 -
31.19; P = 0.61). CONCLUSIONS: We conclude that there is not serological evidence
of an association between T. gondii infection and diabetes mellitus in the
studied subjects in Durango City, Mexico. Further studies to elucidate the role
of T. gondii in diabetes should be conducted.
PMID- 28496552
TI - Screening for Depressive and Anxiety Symptoms During Pregnancy and Postpartum at
a Japanese Perinatal Center.
AB - BACKGROUND: We examined the current status of depressive and anxiety symptoms in
Japanese women during pregnancy and postpartum. METHODS: We asked 220 Japanese
women who gave birth to singleton babies at term to answer the two self
administered questionnaires (Whooley's two questions and two-item generalized
anxiety disorder scale) at first, second and third trimester of pregnancy and 1
month after delivery. RESULTS: The rates of women with depressive symptoms were
common during the first trimester of pregnancy (25%) and the postpartum (17%),
while the women with anxiety symptoms were common during the first trimester of
pregnancy (36%). Eight percent women had histories of mental disorders, and 95%
of them showed depressive and/or anxiety symptoms somewhere during pregnancy. Of
the women who had depressive symptoms during postpartum, 86% showed depressive
and/or anxiety symptoms somewhere during pregnancy. CONCLUSION: Screening for
depressive and anxiety symptoms during pregnancy was suggested to be useful to
detect high risk women of postpartum depression.
PMID- 28496553
TI - Does Syncope Predict Mortality in Patients With Acute Pulmonary Embolism? A
Retrospective Review.
AB - BACKGROUND: Acute pulmonary embolism (APE) is a potentially fatal disease with
high mortality. Prior studies have shown an increased frequency of central
localization of the clot, right ventricular dysfunction and elevated troponin in
patients who present with syncope and APE. Existing evidence regarding mortality
and length of hospital stay in these patients is unclear. METHODS: We
retrospectively reviewed electronic medical records of patients who were admitted
in a tertiary care hospital in rural Upstate New York and diagnosed with APE from
July 2014 to July 2016. Two hundred nineteen patients were reviewed in two
groups: patients who presented with syncope and those without syncope. RESULTS:
The prevalence of syncope was found to be 6.8% (15/219). Hypotension on admission
was more common among patients with syncope compared to no syncope (26.7% and
7.4%, respectively, P = 0.03). A clinically significant difference was found in
30-day mortality among those with syncope versus no syncope (21.3% vs. 7.4%, P =
0.096). No significant difference was found in length of stay (mean 6.7 days in
patients with syncope vs. 6.4 without syncope, P = 0.783), central localization
(26.7% with syncope vs. 43.2% without syncope, P = 0.21) or troponin elevation
(46.2% in patients with syncope vs. 27.9% without syncope, P = 0.205). On
multivariable analysis, hypotension was significantly higher among those with
syncope (odds ratio: 5.23, P = 0.0148). CONCLUSION: This study suggests 30-day
mortality may be higher among patients with syncope. It is important to risk
stratify patients on admission in order to reduce mortality and morbidity
associated with lethal disease.
PMID- 28496555
TI - Effect of Acupressure, Acupuncture and Moxibustion in Women With Pregnancy
Related Anxiety and Previous Depression: A Preliminary Study.
AB - BACKGROUND: In this preliminary study, we examined the effect of acupressure,
acupuncture and moxibustion (oriental treatments) to prevent of the
relapse/deterioration of perinatal depression in women with pregnancy-related
anxiety and previous depression. METHODS AND RESULTS: Between 2014 and 2016,
there were 48 women with pregnancy-related anxiety and previous depression who
had delivery at >= 22 weeks' gestation in our institute. Of these, oriental
treatments were performed in eight and two women (totally 10, 21%) during
pregnancy and postpartum, respectively. One of the 10 (10%) who received oriental
treatments admitted depressive symptoms during pregnancy or postpartum, while 18
of the rest 38 who did not receive oriental treatments admitted depressive
symptoms (47%, P = 0.065). CONCLUSION: The oriental treatments may be useful for
pregnant women who need perinatal mental health care.
PMID- 28496554
TI - Relationship Between Body Mass Index and Obesity Awareness in School Students.
AB - BACKGROUND: The primary aim was to assess the prevalence of overweight and
obesity among the participants and its relationship to obesity awareness.
METHODS: A cross-sectional study that included intermediate and high schools
students was conducted between April 2014 and June 2015. Anthropometric
measurements were obtained by the researchers and body mass index (BMI) was
calculated. We used the obesity risk knowledge (ORK-10) scale to assess obesity
awareness. Participants who answered >= 5 out of 10 questions correctly were
considered to be aware. RESULT: A total of 528 students were enrolled (mean age,
15.58 years). The mean BMI was 22.37 kg/m2, and 27.6% were either overweight or
obese. The mean ORK-10 score was 3.15 and 25.4% were considered to be aware.
Compared to those who were non-aware, participants in the aware group were more
likely to be older (P < 0.001), male (P < 0.001), attend high school (P < 0.001),
eat dinner with their families (P = 0.021), eat fruit at least daily (P = 0.027),
and consider obesity to be a disease (P < 0.001). CONCLUSION: Only 25.4% of
students who participated were considered to be aware about obesity. Those who
were aware were more likely to be older male high school students.
PMID- 28496556
TI - Epidemiological Profile of Hispanics Admitted With Acute Myocardial Infarction in
Puerto Rico: The Experience of 2007, 2009 and 2011.
AB - BACKGROUND: A limited number of studies have been published about coronary artery
disease in Hispanics, particularly among the Puerto Rican population. The aim of
this study was to present a clinical epidemiological profile and management
practices in patients hospitalized in Puerto Rico with acute myocardial
infarction (AMI). METHODS: This secondary data analysis from the Puerto Rico
Cardiovascular Surveillance Study included 6,162 patients at 19 hospitals in
Puerto Rico, during years 2007, 2009 and 2011. RESULTS: The mean age of the
patients diagnosed with AMI was 67 +/- 13.6 years old, with women being older
than men (P < 0.001). Women had a different risk factor burden when compared to
men. Car/walked in was the principal mode of hospital transportation (65.9%).
Women received less medications and cardiac procedures when compared to men.
While no significant differences in length of hospital stay (LOS) were observed
between genders, in-hospital mortality rate was higher in females when compared
with males (6.5% vs. 4.5%; P < 0.001). CONCLUSION: Prompt initiatives should be
implemented to raise awareness, reduce gender disparities and improve outcomes in
patients hospitalized with an AMI in Puerto Rico.
PMID- 28496557
TI - In-Stent Restenosis due to Stent Recoil After Third-Generation Drug-Eluting Stent
Implantation.
AB - A 72-year-old man with a heavily calcified coronary lesion underwent percutaneous
coronary intervention (PCI) using a third-generation drug-eluting stent (DES)
with thin stent struts. Two months after the PCI, in-stent restenosis due to
stent recoil (SR) occurred. An intravascular ultrasound (IVUS) revealed deformed
stent struts and heavily calcified coronary plaque. The SR probably occurred due
to persistent vessel compression as a result of heavily calcified coronary
plaque. We should consider using a DES with thick stent struts rather than a
third-generation DES with thin stent struts in patients with a heavily calcified
coronary lesion.
PMID- 28496558
TI - Using the Native Afferent Nervous System to Sense Bladder Fullness: State of the
Art.
AB - The regulation of micturition involves complex neurophysiologic pathways, and its
understanding has grown immensely over the past decade. Alternative approaches
and applied technologies in the treatment of bladder dysfunction have minimized
the complications that result from neurogenic bladder. The use of natural bladder
mechanoreceptors and electroneneurographic (ENG) signal recordings from afferent
nerves to chronically monitor bladder volume is a promising concept, but the
technology to accomplish this has proven to be a great biomedical engineering
challenge. The focus of this paper will be to describe the current state of ENG
signal recording as a method to detect bladder fullness.
PMID- 28496559
TI - Harvest of Hope: The impact of a church garden project on African American youth
and adults in the rural American South.
AB - A pilot study was conducted of the feasibility of a church garden program to
impact health outcomes in rural African American youth and adults. Thirty-six
workdays were held at a Black church. Pre and post-intervention attitudes, diet,
weight and blood pressure were measured. T-tests were used to test for
significant within group differences. Spearman's rank correlation coefficients
were used to test for significant bivariate associations. Youth showed improved
attitudes about farming and gardening. No statistically significant changes were
observed in adults. Church garden interventions can improve farming and gardening
attitudes for rural, African American youth.
PMID- 28496560
TI - Transmodal Learning of Functional Networks for Alzheimer's Disease Prediction.
AB - Functional connectivity describes neural activity from resting-state functional
magnetic resonance imaging (rs-fMRI). This noninvasive modality is a promising
imaging biomarker of neurodegenerative diseases, such as Alzheimer's disease
(AD), where the connectome can be an indicator to assess and to understand the
pathology. However, it only provides noisy measurements of brain activity. As a
consequence, it has shown fairly limited discrimination power on clinical groups.
So far, the reference functional marker of AD is the fluorodeoxyglucose positron
emission tomography (FDG-PET). It gives a reliable quantification of metabolic
activity, but it is costly and invasive. Here, our goal is to analyze AD
populations solely based on rs-fMRI, as functional connectivity is correlated to
metabolism. We introduce transmodal learning: leveraging a prior from one
modality to improve results of another modality on different subjects. A
metabolic prior is learned from an independent FDG-PET dataset to improve
functional connectivity-based prediction of AD. The prior acts as a
regularization of connectivity learning and improves the estimation of
discriminative patterns from distinct rs-fMRI datasets. Our approach is a two
stage classification strategy that combines several seed-based connectivity maps
to cover a large number of functional networks that identify AD physiopathology.
Experimental results show that our transmodal approach increases classification
accuracy compared to pure rs-fMRI approaches, without resorting to additional
invasive acquisitions. The method successfully recovers brain regions known to be
impacted by the disease.
PMID- 28496561
TI - Effects of Disasters on Smoking and Relapse: An Exploratory Study of Hurricane
Katrina Victims.
AB - BACKGROUND: Psychosocial stress maintains cigarette use and precipitates relapse,
but little is known about how natural disasters in particular affect smoking.
PURPOSE: To determine the feasibility of recruiting victims soon after a natural
disaster for a survey study, and to assess the types and determinants of changes
in smoking behavior resulting from exposure to the disaster. METHODS: A
convenience sample of 35 Hurricane Katrina refugees who had smoked more than 100
cigarettes in their lifetime were surveyed one month after the storm to evaluate
changes in smoking behavior. RESULTS: Among a small sample of former smokers,
more than half relapsed after Katrina, citing stress, urge, and sadness. Among
current smokers, 52% increased their smoking after Katrina by more than half a
pack per day on average. Most individuals who increased their smoking or relapsed
expressed interest in receiving cessation assistance within the next month.
DISCUSSION: Stress-related increases in smoking and relapse may be common after a
natural disaster. TRANSLATION TO HEALTH EDUCATION PRACTICE: Health education
professionals have an important role to play in responding to changes in tobacco
use in the aftermath of disasters. Educational interventions to discourage
tobacco use as a coping strategy may be especially warranted given the high level
of interest expressed in smoking cessation.
PMID- 28496562
TI - Epigenetics of Lipid Phenotypes.
AB - Dyslipidemia is a well-established risk factor for cardiovascular disease, the
main cause of death worldwide. Blood lipid profiles are patterned by both genetic
and environmental factors. In recent years, epigenetics has emerged as a paradigm
that unifies these influences. In this review, we have summarized the latest
evidence implicating epigenetic mechanisms-DNA methylation, histone modification,
and regulation by RNAs-in lipid homeostasis. Key findings have emerged in a
number of novel epigenetic loci located in biologically plausible genes (e.g.
CPT1A, ABCG1, SREBF1, and others), as well as microRNA-33a/b. Evidence from
animal and cell culture models suggests a complex interplay between different
classes of epigenetic processes in the lipid-related genomic regions. While
epigenetic findings hold the potential to explain the interindividual variability
in lipid profiles as well as the underlying mechanisms, they have yet to be
translated into effective therapies for dyslipidemia.
PMID- 28496563
TI - Facilitators and Barriers to HIV Status Disclosure Among HIV-positive MSM Age 50
and Older.
AB - OBJECTIVE: Most HIV-positive men who have sex with men (MSM) ages 50 and older
feel a responsibility to protect their sex partners from HIV transmission risk.
For some, this is enacted through HIV disclosure, for others, this is realized
through reduced risk behaviors. METHODS: To examine this, we analyzed interviews
of 23 HIV-positive MSM ages 50 and older. RESULTS: We identified several
contextual, relational, and psychosocial factors that served as either barriers
or facilitators to HIV disclosure. CONCLUSIONS: Our findings suggest HIV status
disclosure is multifaceted and continues to impact sexual communication in the
lives of MSM as they enter middle age.
PMID- 28496564
TI - In-flight allergic emergencies.
AB - Allergic and hypersensitivity reactions such as anaphylaxis and asthma
exacerbations may occur during air travel. Although the exact incidence of in
flight asthma and allergic emergencies is not known, we have concerns that this
subject has not received the attention it warrants. There is a need to provide
passengers at risk and airlines with the necessary measures to prevent and manage
these emergencies. A review of the epidemiology, management and approaches to
prevention of allergic and asthma emergencies during air travel is presented with
the goal of increasing awareness about these important, potentially preventable
medical events.
PMID- 28496565
TI - An Improved QT Correction Method for use in Atrial Fibrillation and a Comparison
with the Assessment of QT in Sinus Rhythm.
AB - BACKGROUND: Conventional QT corrections may be inappropriate inatrial
fibrillation (AF) due to RR variability and QT lag. Existing formulashave been
modified by the formula RRmod to account for this lag. Wedeveloped a novel
correction formula for use in AF (QTAF) based onthe slope ?QT/?RRmod and report
its performance in AF.We also compare QTAF obtained in AF with rate
independentcorrections in NSR. MATERIALS AND METHODS: A total of 3063 RR/QT pairs
from 28 patients with AFwere measured, 22 of whom also had measurements during
sinus rhythm. QTc (theBazett equation), QTLC (the Framingham linear correction),
and QTAFwere calculated utilizing RRmod, and the rate-independence of eachformula
in AF tested. Mean QTAF values in AF were compared to QTintervals corrected with
QTLC in normal sinus rhythm. RESULTS: ?QTc/?RRmod and?QTLC/?RRmod slopes were
significantlynon-zero whereas ?QTAF/?RRmod was not. QTLCand QTc corrections were
imperfect at extremes of RRmod whileQTAF was constant. QTAF corrections in AF
were shorterthan QTc or QTLC corrections in NSR. CONCLUSIONS: QTAF is a novel QT
correction with adefined relationship to correction in NSR that performs better
than existingstrategies.
PMID- 28496566
TI - Transesophageal Echocardiographyfor Detection Of Left Atrial Appendage Thrombi:
Is It Good Enough?
PMID- 28496567
TI - Classification, Etiology and Clinical Evaluation of Atrial Fibrillation.
PMID- 28496568
TI - Surgical Treatment of Atrial Fibrillation.
AB - Atrial fibrillation (AF) is now commonly treated at the time of valvular heart
surgery or coronary artery bypass grafting. Surgical ablation of AF, which is
predicated upon the Maze procedure, includes creation of lines of conduction
block and excision of the left atrial appendage. A full bi-atrial lesion set is
associated with success in 80% to 95% of patients and virtually eliminates the
risk of late stroke. A complex but safe operation, the classic cut-and-sew Maze
procedure has been applied by relatively few surgeons. However, recent advances
in understanding of the pathogenesis of AF and development of new ablation
technologies enable surgeons to perform pulmonary vein isolation, create linear
left and right atrial lesions, and remove the left atrial appendage rapidly and
safely. Lesions are created under direct vision, minimizing the risk of damage to
the pulmonary veins and adjacent mediastinal structures. Recently developed
instrumentation now enables thoracoscopic and keyhole approaches, facilitating
extension of epicardial AF ablation and excision of the left atrial appendage to
patients with isolated AF and no other indication for cardiac surgery. In
addition, novel devices designed specifically for minimally invasive epicardial
exclusion of the left atrial appendage will broaden the range of treatment
options for patients with AF, possibly eliminating the need for anticoagulation
in selected patients.
PMID- 28496570
TI - Preparing The Electrophysiology Lab to Treat Atrial Fibrillation.
PMID- 28496569
TI - Rate Versus Rhythm Control Pharmacotherapy For Atrial Fibrillation: Where are We
in 2008?
AB - Atrial fibrillation (AF) is the most common sustainedcardiac rhythm disturbance
encountered by physicians. The management of AF isfocused on control of heart
rate, correction of rhythm disturbance, andrisk-determined prophylaxis of
thromboembolism. The goals of AF therapy are, aswith other serious disorders, to
reduce mortality (if possible) and morbidity(improve quality of life, [QOL]). To
this end, several large studies haveexamined rhythm-control versus rate-control
strategies. Although a survivaladvantage to using rhythm control with currently
available antiarrhythmic drugshas not been proven, neither has there been a
significant excess risk versusrate control. Therefore, using our current
therapies, the results have notsupported rate control or rhythm control as being
a preferable first-linetherapy for AF as regards survival; importantly, neither
do they disprove the hypothesis thatmaintenance of sinus rhythm is preferable to
the continuation of AF,particularly if rate control fails to restore adequate
QOL. Many post-hocanalyses and substudies have assessed QOL, functional status,
and exercisetolerance, with the majority demonstrating important benefits
associated withachievement of rhythm control. This review examines rate and
rhythm controloptions, the clinical outcomes of several important AF trials,
discusses thelimitations in applying the major morbidity/mortality findings to
everydayclinical practice, and summarizes the lessons learned.
PMID- 28496571
TI - Characterization of Left Atrial Tachyarrhythmias in Patients Following Atrial
Fibrillation Ablation:Correlation of surface ECG with Intracardiac Mapping.
AB - With expected success rates in excess of 80% for achieving long term arrhythmia
control, catheter based ablation has become a popular treatment strategy in the
management of patients with atrial fibrillation (AF). However, the success of AF
ablation has been tempered by the occurrence of post procedure left atrial
tachycardias and / or flutters, which can be seen in up to 30% of the patients.
These arrhythmias are perpetuated either due to abnormalities of impulse
formation (abnormal automaticity / triggered activity), or abnormalities of
impulse conduction (micro / macroreentry). Regardless of the underlying
mechanism, these tachycardias manifest distinct "P" or flutter waves on the
surface ECG, recognition of which may facilitate their characterization /
localization. However, because of the frequent overlap in the morphology of P
waves, intracardiac mapping is often the only way to distinguish them apart. This
is accomplished using a combination of activation, entrainment and
electroanatomic mapping techniques. Tachycardias resulting from abnormalities of
impulse formation and / or microreentry are characteristically focal and usually
confined in and around pulmonary vein (PV) segments which have reconnected
(septal aspect of right PVs and anterior aspect of left PVs). In contrast,
macroreentrant tachycardias manifest a large circuit dimension involving zone(s)
of slow conduction. These are most commonly seen to occur around the mitral valve
but can develop in any part of the left atrium where "gaps" across prior ablation
lesion sets create altered conduction. Successful ablation of focal tachycardias
is usually accomplished by isolating the reconnected PV segment(s). In case of
macroreentrant arrhythmias however, a more extensive ablation approach is
typically required in order to achieve conduction block across isthmus of the
circuit. Using these strategies, the majority of left atrial tachycardias
occurring post AF ablation can be successfully cured with excellent long term
results.
PMID- 28496573
TI - Antiarrhythmic Effect of Statin Therapy and Atrial Fibrillation A Meta-Analysis
of Randomized Controlled Trials.
AB - The aim of this meta-analysis was to improve the evaluation of the possible
antiarrhythmic effect of statins on atrial fibrillation (AF) incidence
orrecurrence.
PMID- 28496572
TI - Success of Radiofrequency Catheter Ablation of Atrial Fibrillation: Does Obesity
Influence the Outcomes?
AB - Background: Catheter ablation of atrial fibrillation (AF) is an increasingly
popular therapeutic option for symptomatic patients who have failed multiple
antiarrhythmic drugs (AADs). Patients of higher body mass index often fail direct
current cardioversion. The role of body mass index (BMI) on the success of AF
ablation is not well understood. Methods: We prospectively studied 511 patients
who underwent AF ablation at the Cleveland Clinic Foundation between 2002 and
2005. Patients were divided into four classes based on their BMI: Class I ( 25);
Class II (25.1-30); Class III (30.1-35) and Class IV (>35). These groups were
compared for baseline demographic and clinical characteristics. Any recurrence of
AF after 3 months of ablation was considered as failure. All classes were
followed for at least 12 months and rates of failure were compared. Results:
Based on their BMI, 25% of patients were assigned to class I, 37% in class II,
21% in class III and 16% in class IV. Patients of higher classification (class
III or IV) were more likely to be male (p<0.001), diabetic (p<0.001), smokers
(p=0.002), with coronary artery disease (=0.018), left atrial enlargement
(p=0.015) and longstanding AF (p=0.007). Severity of obesity as measured by BMI
had a direct correlation to early (p=0.05) and late (p=0.01) recurrence of AF.
Conclusion: Obesity is significantly associated with long-term AF recurrence
after catheter ablation. Higher incidence of smoking & left atrial enlargement
may possibly contribute to higher failure rates in this sub-group of patients.
PMID- 28496574
TI - Long-Termendurance Sport Practice Increases The Incidence Of Lone Atrial
Fibrillation Inmen: A Follow-Up Study.
PMID- 28496575
TI - AF Termination: the Holy Grail of Persistent AF Ablation?
PMID- 28496576
TI - Pre-Procedural Imaging to Direct Catheter Ablation of Atrial Fibrillation:
Anatomy and Ablation Strategy.
AB - Successful catheter ablation of atrial fibrillation (AF) requires a detailed
understanding of left atrial anatomy in order to maximize the safety and efficacy
of the procedure. Common and rare variants of left atrial and pulmonary venous
anatomy have been described which can affect the optimal ablation strategy for
each individual patient. These variants include the presence of a right or left
middle pulmonary vein, a left or right common pulmonary vein, a common inferior
pulmonary vein, a right top pulmonary vein, and other rare forms of anomalous
pulmonary venous drainage. There are also important patient-specific differences
in pulmonary venous ridges and left atrial roof morphology. Pre-procedural CT or
MR imaging can define these anatomic variants in exquisite detail and be used
with image-integration strategies to direct the ablation procedure. In this
review, we describe common and uncommon variants that can be identified by pre
procedural imaging, and suggest ablation strategies tailored to these anatomic
variants.
PMID- 28496577
TI - Trigger Versus Substrate Ablation for Atrial Fibrillation.
AB - Elimination of triggers has become the hallmark of catheter ablation of atrial
fibrillation (AF). In particular, much attention has been paid to the elimination
of triggering impulses from the pulmonary veins via pulmonary vein ablation
procedures. While this approach has a proven track record for paroxysmal AF, the
efficacy in non-paroxysmal AF has been less convincing. Thus, attention has been
paid to elimination of the substrate responsible for AF perpetuation, including
complex fractionated electrograms, dominant frequency sites, and autonomic
ganglionated plexi. None of these targets has yet become mainstream, but they are
all under active investigation. As our knowledge of these targets increases and
clinical studies are performed, a more refined approach to AF ablation will
surely emerge.
PMID- 28496579
TI - Intracardiac ECHO Integration with Three Dimensional Mapping: Role in AF
Ablation.
AB - Background: Catheter ablation of atrial fibrillation (AF) is typically guided by
3D mapping. This involves point-by-point reconstruction of the 3D virtual anatomy
and may be time consuming and require substantial fluoroscopy exposure.
Intracardiac echocardiography (ICE) affords real time imaging of the cardiac
structures during mapping and ablation. Methods: Between February and May 2007,
15 patients (100% men, 10 with paroxysmal AF) presenting for AF ablation were
offered mapping using a novel system integrating 3D mapping and ICE. A modified
ICE probe with a location sensor tracked by the mapping system was positioned in
the right atrium (RA). This allowed acquisition of ECG gated images of the left
atrium (LA). Endocardial contours were traced on each image and were used to
generate a registered 3D map. Results: 3D maps took a mean of 51+/-25 minutes to
create, PRIOR to entering the LA and without fluoroscopy. Pulmonary veins and the
esophagus were rendered in 3D. A complete map was built from a mean of 46+/-19
contours. Upon instrumentation of the left atrium, the maps were easily distorted
if points collected by the mapping catheter were combined with the original map,
due to deformation of the left atrial geometry by the relatively stiff ablation
catheter. Pulmonary vein antrum isolation was guided by a circular mapping
catheter. Since this catheter could not be visualized on the CARTO map,
fluoroscopy was used to track its position and the contact between the ablation
catheter and the circular mapping catheter. No substantial reduction in
fluoroscopy time was thus realized, as expected. At 10+/-1 months of followup,
73% of the patients were in sinus rhythm after the initial three month blanking
period. No patient suffered any complications related to the procedure or in
follow-up. Conclusions: A mapping system combining ICE and 3D electroanatomical
mapping can feasibly reconstruct a 3D shell of the LA and the pulmonary veins
without the need to enter the left heart. The map created is sensitive to
distortion during point-by-point mapping with the standard ablation catheter.
PMID- 28496580
TI - Skin Burn at the Site of Indifferent Electrode after Radiofrequency Catheter
Ablation of AV Node for Atrial Fibrillation.
AB - Radiofrequency Ablation of AV node with permanent pacemaker has been used to
achieve rate control in persistent symptomatic atrial fibrillation. Although RF
Ablation is safe, complications may occur in up to 3% of the procedures. A rare
complication of 2nd degree skin burn at indifferent electrode site has been
described here. This report highlights the rare but possible complication in
patients undergoing such a procedure and help in preventing by taking appropriate
measures.
PMID- 28496581
TI - Is Empirical Four Pulmonary Vein Isolation Necessary for Focally Triggered
Paroxysmal Atrial Fibrillation? Comparison of Selective Pulmonary Vein Isolation
Versus Empirical Four Pulmonary Vein Isolation.
PMID- 28496582
TI - Catheter Ablation for Atrial Fibrillation in Patients with Obesity.
PMID- 28496584
TI - Design of an Outpatient Atrial Fibrillation of Excellence: Current Experience
with the Deliver of Pre and Post Procedure Care.
PMID- 28496583
TI - Atrial Fibrillation and Heart Failure.
AB - Atrial fibrillation is common in heart failure patients and is associated with
increased mortality. Pharmacologic trials have not shown any survival benefit for
a rhythm control over a rate control strategy. It has been suggested that sinus
rhythm is associated with a survival benefit, but that the risks of anti
arrhythmic drug treatment and poor efficacy offset the beneficial effect.
Catheter ablation for atrial fibrillation can establish sinus rhythm without the
risks of anti-arrhythmic drug therapy. Data from randomized trials demonstrating
a survival benefit for patients undergoing an ablation procedure for atrial
fibrillation are still lacking. Ablation of the AV junction and permanent pacing
remain a treatment alternative in otherwise refractory cases. Placement of a
biventricular system may prevent or reduce negative consequences of chronic right
ventricular pacing. Current objectives and options for treatment of atrial
fibrillation in heart failure patients are reviewed.
PMID- 28496585
TI - Cardiac Image Registration.
AB - Long procedure time and somewhat suboptimal results hinder the widespread use of
catheter ablation of complex arrhythmias such as atrial fibrillation (AF). Due to
lack of contrast differentiation between the area of interest and surrounding
structures in a moving organ like heart, there is a lack of proper
intraprocedural guidance using current imaging techniques for ablation. Cardiac
image registration is currently under investigation and is in clinical use for AF
ablation. Cardiac image registration, which involves integration of two images in
the context of the left atrium (LA), is intermodal, with the acquired image and
the real-time reference image residing in different image spaces, and involves
optimization, where one image space is transformed into the other. Unlike rigid
body registration, cardiac image registration is unique and challenging due to
cardiac motion during the cardiac cycle and due to respiration. This review
addresses the basic principles of the emerging technique of registration and the
inherent limitations as they relate to cardiac imaging and registration.
PMID- 28496586
TI - Sinus Node Dysfunction in Atrial Fibrillation: Cause or Effect?
PMID- 28496587
TI - Impact of Smoking on the Atrial Substrate Characteristics in Patients with Atrial
Fibrillation.
PMID- 28496589
TI - Echocardiographic Predictors of Symptomatic Atrial Fibrillation In Patients with
Rheumatic Mitral Stenosis and Normal Sinus Rhythm.
AB - : Introduction: Rheumatic mitral stenosis (RMS) increases the risk of both atrial
fibrillation (AF) and thromboembolism. Methods: Patients with mitral stenosis and
normal sinus rhythm were enrolled in the study prospectively.The present study
was designed to study whether echocardiographic evaluation in patients with
mitral stenosis and normal sinus rhythm could predict the occurrence of
symptomatic AF . RESULTS: Sixty-two patients (51 females) with mitral stenosis
and normal sinus rhythm were included in the study. Seven patients (11.3%)
developed symptomatic AF and the remaining 55 were free of AF during a followed
up of 22+/-5 months. The following echocardiographic parameters were
significantly increased and predicted the development of AF; left atrial (LA)
mediolateral diameter (5.5 +/- 0.5 cm vs 4.7 +/- 0.7 cm), right atrial
mediolateral diameter (4,7 +/- 1.0 cm vs 3.6 +/- 1.3 cm), LA area in the apical
two chamber view ( 31 +/- 3.2 cm2 vs 25 +/- 5.8 cm2), right atrial volume (52 +/-
22 cm3 vs 34 +/- 19 cm3), and interatrial conduction time (IACT) (142 +/- 22 msec
vs 115 +/- 16 msec). Conclusions: This study revealed that echocardiography can
be used to predict symptomatic AF in patients with RMS and sinus rhythm.
PMID- 28496590
TI - GIANT Flutter Waves in ECG Lead V1: a Marker of Pulmonary Hypertension.
AB - Atrial flutter (AFl) may exist with or without underlying structural heart
disease. Typical AFl presents as a "sawtooth" pattern on the ECG - with inverted
flutter (F) waves in the inferior leads and upright F waves in V1. This
morphology offers no direct clues as to the underlying cardiac disorder, if any.
Occasionally we have encountered giant F waves, most prominently in lead V1,
reaching 5 mv or more in height - sometimes exceeding the QRS voltage. The
significance of this pattern has not been investigated and reported on. To
determine if giant F waves in V1 provide any insight into the
presence/type/absence of specific underlying cardiac pathology, the history of 6
consecutive patients with giant F waves was reviewed. Upon review, the only
factor common to each patient was the presence of or history of pulmonary
hypertension. Right ventricular dilation and/or dysfunction and right atrial
enlargement with or without tricuspid insufficiency were present in each by
echocardiography. Giant F waves appear to occur in the setting of right heart
dysfunction in patients with a history of or the continued presence of pulmonary
hypertension. Their detection should indicate the need for right heart
evaluation.
PMID- 28496588
TI - Atrial Septal Defect and Atrial Fibrillation: The Known and Unknown.
AB - Atrial fibrillation (AF) is a common complication in patients with atrial septal
defects (ASDs). The link between AF and ASD is fairly complex and entails
modifications in electrophysiologic, contractile and structural properties, at
the cellular and tissue level, of both atria, mainly due to chronic atrial
stretch and dilation. Surgical repair or percutaneous closure of ASDs are equally
effective in reducing mortality and symptoms but limited in preventing or curbing
AF, unless combined with an arrhythmia-specific procedure. Transesophageal
echocardiography (TEE) and intracardiac echocardiography (ICE) have improved the
safety and success of the above procedures. Finally, clearer understanding of the
pathophysiology of AF in patients with ASD (and CHF, in general) has led to
target-specific advances in medical management.
PMID- 28496591
TI - Underutilization of Warfarin Therapy in Elderly Patients with Atrial Fibrillation
- Fear or False Sense of Security!
AB - Background: Under utilization of warfarin in elderly patients with atrial
fibrillation (AF) has been recognized as a significant health care issue. This
study examines the rate and reasons for warfarin underutilization in elderly
patients with AF at the Kansas City Veterans Affairs Medical Center. Methods:
Retrospective study reviewing electronic medical records of all patients aged 65
and older with the diagnosis of atrial fibrillation. Patients on warfarin were
excluded. Reasons for not using warfarin were extracted by reviewing the
electronic medical record. Anticoagulation indications for these patients were
determined based on the ACC/AHA/ESC 2006 Guidelines for the Management of
Patients with Atrial Fibrillation. Results: Warfarin was not used by 407 patients
(25%) with known AF. Average age was 79+6.2 years. 60% of patients had persistent
or permanent AF. Prevalence of risk factors for thromboembolism included
hypertension (74%), heart failure or ejection fraction of <40% (21%), diabetes
(27%) and coronary artery disease (48%). CHADS (2) scores were documented in the
charts less than 1% of the times. Only 11 patients had CHADS (2) score of 0 and
70 had a score of 1. A class I or IIa indication for warfarin therapy was present
in 298 (73%) of patients. Return to sinus rhythm (37%) was the most common reason
for not using warfarin. In 30% of cases the reason not to use warfarin was not
addressed. Other reasons not to use warfarin included fear of falls (7%), prior
head or GI bleed (14%), patient refusal & noncompliance (12%). History of CVA or
TIA was documented in 12% of patients. Conclusions: Underutilization of warfarin
in elderly patients with atrial fibrillation remains a common problem despite
their high risk for thromboembolic events. A false sense of security about the
paroxysmal nature of AF, lack of proper insight about stroke risk (CHADS (2)),
and fear of bleeding are the most common reasons for non use of warfarin.
PMID- 28496592
TI - Physical Activity and Incidence of Atrial Fibrillation in Older Adults: The
Cardiovascular Health Study.
PMID- 28496593
TI - Left Atrial Image Registration to Guide Catheter Ablation of Atrial Fibrillation:
In the Eye of the Technology.
PMID- 28496594
TI - Periablative Anticoagulation Strategies in Patients with Atrial Fibrillation.
AB - Atrial fibrillation is associated with thromboembolic events that may cause
important impairment on quality of life. Pulmonary vein isolation is the
treatment of choice in cases that are refractory to medical therapy. Once sheaths
and catheters are manipulated inside the left atrium, anticoagulation with
heparin must be used during the procedure to protect patients from thromboembolic
phenomena. Different strategies of anticoagulation are used at different centers.
This review summarizes the pathophysiology of thrombus formation in the left
atrium, defines which patients are under high risk and describes the main
strategies used for anticoagulation.
PMID- 28496595
TI - Catheter Abalation for AF : Past, Present and Future.
PMID- 28496596
TI - Leukocyte-Aprotinin Atrial Fibrillation Study (LAFFS): Impact of Aprotinin and
Leukofiltration on Atrial Fibrillation, Renal Insufficiency and Encephalopathy
Post-Cardiopulmonary Bypass.
AB - Purpose: Atrial fibrillation remains the leading postoperative complication
following cardiopulmonary bypass. A randomized trial was undertaken to evaluate
the effectiveness of leukocyte filtration and aprotinin, applied separately and
in combination, on the incidence of post-operative atrial fibrillation. A
secondary component of the study was the impact of these adjunct interventions on
post-surgical renal and neurological dysfunction. Methods: A total of 1,220
patients undergoing primary isolated coronary artery bypass grafting were
randomly assigned to one of four treatment groups. The control group (305
patients) received standard cardiopulmonary bypass with moderately hypothermic
(34oC) cardioplegic arrest. In the filtration group (310 patients) leukocyte
reducing filters were incorporated into the bypass circuit and deployed
strategically. The aprotinin group (285 patients) received full Hammersmith dose
aprotinin. The combination therapy group (320 patients) received both aprotinin
and leukocyte filtration. Results: The incidences of atrial fibrillation were 25%
in the control group, 16% in the filtration group, 19% in the aprotinin group and
10% in the combination therapy group (P < 0.001). Renal dysfunction was detected
in 3% of the control group, 2% of the filtration group, 8% of the aprotinin
group, and 5% of the combination group (P < 0.005). Neurological dysfunction
occurred in 2% of the control group, 2% of the filtration group, 1% of the
aprotinin group, and 2% of the combination group (P = n.s.). Conclusions:
Combination therapy with aprotinin and leukocyte filtration markedly reduced
atrial fibrillation post-cardiopulmonary bypass, and was more effective than the
individual treatments. Aprotinin treatment increased the incidence of renal
dysfunction, and the addition of leukocyte filtration partially mitigated this
detrimental effect of aprotinin. Thus, strategic leukocyte filtration augments
aprotinin's anti-arrhythmic effects while suppressing its nephrotoxic sequelae.
PMID- 28496597
TI - Typical Flutter Ablation as an Adjunct to Catheter Ablation of Atrial
Fibrillation.
AB - During the past decades there has been a consistent evolution of both surgical
and catheter-based techniques for the treatment of stand-alone atrial
fibrillation, as alternatives or in combination with anti-arrhythmic drugs.
Transcatheter ablation has significantly improved outcomes, despite often
requiring multiple procedures and with limited success rates especially in
presence of persistent atrial fibrillation. Surgical procedures have dramatically
evolved from the original cut-and-sew Maze operation, allowing nowadays for
closed-chest epicardial ablations on the beating heart. Recently, the concept of
a close collaboration between the cardiac surgeon and the electrophysiologist has
emerged as an intriguing option in order to overcome the drawbacks and suboptimal
results of both techniques; therefore, the hybrid approach has been proposed as a
potentially more successful strategy, allowing for a patient-tailored
therapeutical approach. We reviewed the recent advancements either from the
transcatheter and surgical standpoint, with a peculiar focus on the current
option to merge both techniques along with an up-to-date review of the
preliminary clinical experiences with the hybrid, surgical-transcatheter
treatment of stand-alone atrial fibrillation.
PMID- 28496598
TI - Extra Atrial Disease in Patients with "Lone" Atrial Fibrillation.
AB - AIMS: Lone atrial fibrillation (LAF) is considered by some to be a primary atrial
electrophysiologic disorder. However, we have frequently observed evidence of
"extraatrial" diseases - atherosclerosis and associated metabolic disorders - in
our LAF patients. We sought to characterize and quantify extraatrial disease
burden in LAF patients, and to correlate this burden with features of the
arrhythmia including pattern (paroxysmal versus persistent) and response to
catheter ablation. METHODS AND RESULTS: Forty-six consecutive patients with non
familial LAF underwent assessment for evidence of atherosclerosis (computed
tomographic vascular calcification and elevated arterial pulse wave velocity) and
associated metabolic diseases (dyslipidemia, insulin resistance and
inflammation), and then catheter ablation. The cohort had a significant incidence
of atherosclerosis (57%) and metabolic (70%) diseases. Patients with persistent
AF tended to have a greater extraatrial disease burden than those with paroxysmal
AF. A significant inverse relationship between the rate of ablation success and
extraatrial disease burden was demonstrated. CONCLUSIONS: Extraatrial disease was
common in this LAF cohort. Correlations between extraatrial disease burden and
features of the arrhythmia would, if verified, challenge the notion that LAF is a
"primary" electrophysiologic disorder.
PMID- 28496599
TI - The Anticoagulated Atrial Fibrillation Patient Who Requires "Curative" Therapy
for Prostate Carcinoma: a Bleeding Conundrum.
PMID- 28496600
TI - Role of the Auotnomic Nerves system in the Creation of Substrate for Atrial
Fibrillation.
PMID- 28496601
TI - Quality of Life, Exercise Capacity and Comorbidity in Old Patients with Permanent
Atrial Fibrillation.
AB - : Background: The impact of atrial fibrillation (AF) on quality of life (QoL)
differs with the AF population studied and is influenced by comorbidity. In
hospital-based studies younger and highly symptomatic patients may be
overrepresented. We performed an observational cross sectional study in two
municipalities, comparing 75 year-old patients with and without permanent atrial
fibrillation, with respect to health-related QoL and exercise capacity, with
adjustment for the effects of confounders. Methods: Maximal treadmill exercise
testing provided peak oxygen uptake (VO2 peak). Health-related QoL was assessed
by self-completed SF-36 questionnaires. The lowest quartile identified poor
outcomes. RESULTS: 27 subjects with permanent AF and 71 subjects in sinus rhythm
participated. AF patients had higher prevalence of compensated chronic heart
failure (p < 0.001), valvular heart disease (p < 0.001), lower mean VO2 peak
(22.7 +/- 5.5 vs. 28.6 +/- 6.3 ml/kg/min; p < 0.001), and more often poor VO2
peak; crude OR 5.3 (95%CI 1.8, 15.3), adjusted OR 7.5 (2.0, 28.3). Median
Physical Component Summary score (with 25th and 75th percentile) was 41 (31, 51)
in AF vs. 52 (45, 55) in controls (p < 0.001). Furthermore, the AF group had
higher odds for poor physical QoL scores; crude OR 5.0 (1.8, 13.7), adjusted OR
4.3 (1.5, 12.4). Median Mental Component Summary score was 56 (42, 61) in the AF
group vs. 57 (51, 60) in controls (p=0.565). The AF group had non-significantly
increased odds for poor mental QoL scores; crude OR 2.3 (0.8, 6.2), adjusted OR
2.8 (1.0, 8.4). Conclusion: Also after adjustment for confounders, older patients
with permanent AF had higher odds for poor exercise capacity and poor physical
QoL compared to subjects in sinus rhythm.
PMID- 28496602
TI - The A That Did Not Fib:Two Roads Both Traveled By.
AB - Case: A 64-year-old woman presented with palpitations. Her 24-hour Holter monitor
revealed runs of presumed atrial fibrillation (AF). The patient was referred for
EP study and AF ablation. EPS: At EPS, an anterograde A-H jump was noted.
Spontaneous bursts of tachycardia were seen, consisting of sinus atrial beats
with dual ventricular responses, each preceded by a His deflection. There was no
atrial fibrillation during the study. Radiofrequency ablation of the slow AV node
pathway was performed. There were no inducible tachycardias and no A-H jump
following the ablation. The patient had no recurrence post-procedure. Discussion:
This case presents a rare example of simultaneous dual anterograde AV-nodal
conduction. The conditions leading to this phenomenon include dual AVN pathways,
markedly slowed conduction in the slow pathway, and lack of retrograde conduction
up either pathway such that reentry was impossible. An irregular, narrow-complex
tachycardia resulted, initially interpreted as AF. Slow-pathway ablation was
curative.
PMID- 28496603
TI - Atrial Fibrillation: a Patient's Guide to Understanding Drug Therapy.
PMID- 28496604
TI - Do Statins Decrease the Arrhythmia Burden in Patients with Paroxysmal Atrial
Fibrillation?
PMID- 28496605
TI - Is Rhythm Control with Pulmonary Vein Isolation Superior to Rate Control with AV
Nodal Ablation in Patients with Heart Failure?
PMID- 28496606
TI - Are Balloon Based Strategies Better Than Conventional Radiofrequency Catheter
Ablation: Exploring New Frontiers In The Treatment Of Atrial Fibrillation.
AB - Paroxysmal atrial fibrillation can be eliminated with continuous circular linear
lesions around the pulmonary veins using radiofrequency ablation. Due to the
technical complexity of this procedure balloon-based devices have been developed
to simplify pulmonary vein isolation. Cryoballoon ablation provides excellent
safety and is technically less demanding when compared to radiofrequency catheter
ablation in selected patients. In this review, advantages as well as drawbacks of
this emerging technology in relation to standard catheter ablation are discussed.
PMID- 28496607
TI - QT Prolongation Following Ectopic Beats: Initial Data Regarding The Upper Limit
Of Normal With Possible Implications For Antiarrhythmic Therapy And Concealed
(Unexpressed) Long QT.
AB - : Background: Ectopic beats are frequently associated with morphologic
repolarization alterations of ensuing sinus beats. Less is known about
repolarization duration alterations of post-ectopic sinus beats. In one patient
who developed long QT and torsades de pointes upon exposure to a class III
antiarrhythmic drug, and was later genotyped as being a carrier for long QT
syndrome (LQTS) type 1, review of a pre-drug Holter monitor study revealed marked
QT prolongation of post-ectopic sinus beats. In wondering whether this might be a
common clue to "concealed" unexpressed LQTS, we realized that we must first
characterize the range of post-ectopic QT prolongation present in normals.
Prolongation beyond the upper limit of this range might then raise suspicion of
possible LQTS and alter the antiarrhythmic drug selection process for the
suppression of atrial fibrillation or other arrhythmias. Methods: Accordingly, we
assessed the presence/degree of repolarization prolongation following premature
ectopic impulses in 166 subjects with normal conduction intervals and normal
repolarization on their resting 12-lead ECG, 75 of whom had no known associated
cardiovascular disorder of any kind. That is, in our subjects, the maximal
prolongation of the QT interval of the sinus beat following isolated ventricular
and atrial premature complexes was characterized. Results: QT prolongation is
common in post ectopic sinus beats. However, in our subjects the uncorrected QT
interval of post-ectopic sinus beats never exceeded 480 ms in duration [which was
much shorter than that seen (510-590 ms) in our gene carrier]. CONCLUSIONS: The
QT interval in normal subjects may prolong following premature complexes but not
to a value in excess of 480 ms.
PMID- 28496608
TI - Atrial Fibrillation And Coronary Heart Disease:Fatal Attraction.
AB - In this manuscript, the profile and clinical management of hypertensive patients
with chronic ischemic heart disease and atrial fibrillation (AF) is examined and
whether high heart rate is associated with a different profile is determined.
CINHTIA was a cross-sectional and multicenter survey aimed to define the clinical
profile of hypertensive patients with chronic ischemic heart disease daily
attended in Spain. Blood pressure, LDL-cholesterol and diabetes control rates
were established according to ESHESC 2003, NCEP-ATP III and ADA 2005 guidelines,
respectively. Out of the 2024 patients, 338 (16.7%) exhibited AF. The group of
patients with AF was older and with higher prevalence of diabetes, organ damage
and cardiovascular disease. Blood pressure (41.8% vs 34.5%, p=0.014) and diabetes
(28.5% vs 20.9%,p=0.044) were worse controlled in patients with AF, with a trend
to a lower control of LDL-cholesterol (31.2% vs 26.8%, p=0.093). When
distributing patients with AF according to heart rate, except for smoking, left
ventricular hypertrophy and peripheral arterial disease that were more frequent
in those with higher heart rate, no significant differences were found in other
risk factors or organ damage between groups. Blood pressure, glycemia and LDL
cholesterol were worse controlled in the subgroup with highest heart rate. In
clinical practice, hypertensive patients with chronic ischemic heart disease and
AF have a bad prognosis not only due to a worse clinical profile, but also due to
lower risk factors control rates. In contrast with patients at sinus rhythm,
higher heart rate was less related with a worse clinical profile in subjects with
AF.
PMID- 28496609
TI - Anticoagulation During AF Ablation: The Balance between Thromboembolism and
Bleeding.
AB - Radiofrequency ablation for atrial fibrillation is being increasingly used to
treat patients with symptomatic arrhythmia. The procedure is complex and
associated with significant complications including thromboembolism, stroke, and
bleeding. Despite significant advances in catheter design, online cardiac
imaging, and greater operator experience, both stroke and major vascular
complications continue to be problematic. Increasing the duration and intensity
of anticoagulation has been the primary modality used to decrease
thromboembolism. However, these measures increase the likelihood and severity of
bleeding-related complications. The optimal method of anticoagulation along with
the adjunctive use of technology to decrease vascular complications and
mechanically prevent cerebral embolization is unknown. In this paper, we review
the present methods used by ablationists to decrease the likelihood of
thromboembolism during atrial fibrillation. We then describe methods used to
decrease bleeding and vascular complications at access sites as well as cardiac
perforation. We briefly discuss newer techniques to decrease endovascular
complications including epicardial ablation and the use of temporarily implanted
vascular protection devices.Finally, we describe the best option or combination
of approaches that attempt to balance the risks of thromboembolism and bleeding
during AF ablation..
PMID- 28496610
TI - Presence Of Left Atrial Appendage Thrombus In Patients Presenting For Left Atrial
Ablation Of Atrial Fibrillation Despite Pre-Operative Anticoagulation.
AB - Background: One of the recognised complications of left atrial ablation for
atrial fibrillation (AF) is stroke. Left atrial (LA) thrombus, which may be
dislodged by catheter manipulation, is an absolute contraindication to ablation.
It is unclear whether imaging of the left atrial appendage (LAA) by
transesophageal echo (TEE) is mandatory to exclude LA clot prior to ablation,
particularly in "low-risk" patients with paroxysmal AF and normal left
ventricular (LV) function. Methods and Results: We carried out a retrospective
analysis of pre-ablation TEE in patients presenting for ablation of AF. Images
from 244 ablation procedures carried out in 148 patients were examined, including
106 patients with paroxysmal AF and normal LV function. Despite at least 4 weeks
of pre-operative therapeutic anticoagulation with Warfarin (INR>2.0), LAA
thrombus was identified in 4 patients (2.7% (0.1-5.3%)). These included 2
patients with paroxysmal AF and normal LV function, although both had a high
arrhythmia burden. The thrombi regressed with intensification of anticoagulation.
Conclusions: Pre-operative imaging of the LAA remains advisable to exclude
thrombus prior to ablation for AF even in patients with paroxysmal AF and normal
LV function, especially if there is a high AF burden.
PMID- 28496611
TI - Atrial Fibrillation Progression: New Insight in TheNatural History of This
Arrhythmia.
PMID- 28496612
TI - Review on "High-Density Mapping of Atrial Fibrillation in Humans: Relationship
Between High-Frequency Activation and Electrogram Fractionation".
PMID- 28496613
TI - 14th Annual Boston Atrial Fibrillation Symposium Proceedings - Technology Round
Up.
PMID- 28496614
TI - Cardiovascular Risk Factors and Atrial Fibrillation: What is the Link?
PMID- 28496615
TI - Accurate Detection Of Left Atrial Thrombus Prior To Atrial Fibrillation Ablation
In Patients With Therapeutic Anticoagulation: Does Transesophageal
Echocardiography Beat Conventional Wisdom?
PMID- 28496616
TI - Genetics and Sinus Node Dysfunction.
PMID- 28496618
TI - Predictors of Success After a First Circumferential Pulmonary Vein Isolation For
Atrial Fibrillation.
AB - Background: To identify and characterise pre-procedural and procedural parameters
which predict maintenance of sinus rhythm after a first circumferential pulmonary
vein isolation (CPVI) for recurrent atrial fibrillation (AF). Methods: 100
patients (54+/-10 yrs) undergoing CARTO-guided CPVI for symptomatic drug
refractory, paroxysmal or shortstanding persistent AF were studied. The endpoint
was complete electrical isolation within the encircled regions. 3D left atrial
(LA) volume was measured by CARTO geometry. Follow-up examinations (symptoms,
ECG, 24-hour ECG recording) were performed at 1 and 3 months and every 3 months
thereafter. Results: After the first CPVI, 71 patients (71%) were free of AF
without antiarrhythmic drug therapy (follow up:28+/-11 months). The only
independent and significant predictors for freedom of AF after the first CPVI
were duration of AF history and 3D LA volume (p<0.05). However, a significant
overlap in durations of AF history and 3D LA volumes between failures and
successes was observed. Conclusions: (1) Using the "circumferential pulmonary
vein isolation" approach, the first catheter ablation leads to resolution of
arrhythmia in ~ 70% of symptomatic AF patients. (2) Independent predictors for
freedom of AF after initial CPVI are duration of AF history and 3D LA volume. (3)
Due to considerable overlap between failures and successes, these parameters can
not be used to identify patients who should not undergo CPVI or in whom an
additional ablation beyond CPVI is required. On the other hand, our results do
suggest that an ablation strategy early in the course of AF disease can influence
successful outcome.
PMID- 28496619
TI - Is Cryo a Better Energy Source Than Radiofrequency for AF Ablation in Preventing
Esophageal Injury?
PMID- 28496620
TI - Ectopic Triggers of Superior Vena Cava in Atrial Fibrillation.
PMID- 28496621
TI - Scenes from a CFAE: Complex Fractionated Atrial Electrogram Map in a Woman with
Longstanding Persistent Atrial Fibrillation Following Mechanical Mitral Valve
Replacement.
AB - Case: A 62-year-old woman was referred for atrial fibrillation (AF) ablation. She
had longstanding persistent AF for 8 years since mechanical mitral valve
replacement for rheumatic heart disease. EPS: A strategy of substrate-based
ablation targeting areas of complex fractionated atrial electrograms (CFAE) was
pursued. These sites were identified by inspection of electrograms and verified
with software-based electrogram analysis, with the left atrial roof demonstrating
the highest density of CFAE sites. Successful catheter ablation was performed.
The patient has remained free of recurrence over 4 months of follow-up.
Discussion: This case presents a successful ablation procedure using the emerging
strategy of CFAE-targeted ablative lesions. Given the patient's longstanding
persistent AF and mechanical mitral valve, the high density of CFAE sites on the
left atrial roof was an unexpected finding. Analysis for CFAE sites guided the
procedure in a direction that might otherwise not have been undertaken, leading
to a successful ablation.
PMID- 28496617
TI - Atrial Fibrillation: The New Epidemic of the Ageing World.
AB - The prevalence of atrial fibrillation (AF) increases with age. As the population
ages, the burden of AF increases. AF is associated with an increased incidence of
mortality, stroke, and coronary events compared to sinus rhythm. AF with a rapid
ventricular rate may cause a tachycardia-related cardiomyopathy. Immediate direct
current (DC) cardioversion should be performed in patients with AF and acute
myocardial infarction, chest pain due to myocardial ischemia, hypotension, severe
heart failure, or syncope. Intravenous beta blockers, diltiazem, or verapamil may
be administered to reduce immediately a very rapid ventricular rate in AF. An
oral beta blocker, verapamil, or diltiazem should be used in persons with AF if a
fast ventricular rate occurs at rest or during exercise despite digoxin.
Amiodarone may be used in selected patients with symptomatic life-threatening AF
refractory to other drugs. Digoxin should not be used to treat patients with
paroxysmal AF. Nondrug therapies should be performed in patients with symptomatic
AF in whom a rapid ventricular rate cannot be slowed by drugs. Paroxysmal AF
associated with the tachycardia-bradycardia syndrome should be treated with a
permanent pacemaker in combination with drugs. A permanent pacemaker should be
implanted in patients with AF and symptoms such as dizziness or syncope
associated with ventricular pauses greater than 3 seconds which are not drug
induced. Elective DC cardioversion has a higher success rate and a lower
incidence of cardiac adverse effects than does medical cardioversion in
converting AF to sinus rhythm. Unless transesophageal echocardiography has shown
no thrombus in the left atrial appendage before cardioversion, oral warfarin
should be given for 3 weeks before elective DC or drug cardioversion of AF and
continued for at least 4 weeks after maintenance of sinus rhythm. Many
cardiologists prefer, especially in elderly patients , ventricular rate control
plus warfarin rather than maintaining sinus rhythm with antiarrhythmic drugs.
Patients with chronic or paroxysmal AF at high risk for stroke should be treated
with long-term warfarin to achieve an International Normalized Ratio of 2.0 to
3.0. Patients with AF at low risk for stroke or with contraindications to
warfarin should be treated with aspirin 325 mg daily.
PMID- 28496623
TI - JAFIB : A Comprehensive Resource for Afib ....
PMID- 28496622
TI - Biatrial, 3-Dimensional Mapping of Human Atrial Fibrillation: Methodology and
Clinical Observations.
PMID- 28496624
TI - Assessing Patient Management and Outcomes in Atrial Fibrillation: Does your
Health Insurance Plan know more than your Doctor?
PMID- 28496626
TI - Atrial Fibrillation Complicating Congestive Heart Failure: Electrophysiological
Aspects And Its Deleterious Effect On Cardiac Resynchronization Therapy.
AB - More successful recognition and treatment of cardiovascular risk factors and
diseases continues to decrease mortality and increase the proportion of elderly
population. Therefore, there are more people with increased risk of developing
heart failure and atrial fibrillation in the course of their lives. Atrial
fibrillation (AF) can complicate the course of congestive heart failure (HF)
leading to acute pulmonary edema. The prevalence of AF, in patients with heart
failure, increases with the severity of the disease, reaching up to 40% in
advanced cases. In these HF patients, AF is an independent predictor of morbidity
and mortality increasing the risk of death and hospitalization. Despite the
excellent results obtained with different drugs, the optimal medical treatment
can fail in the intention to improve symptoms and quality of life of patients
with severe HF. Thus, the necessity to use cardiac devices emerges facing the
failure of optimal medical treatment in order to achieve hemodynamic improvement
and correction of the physiopathological alterations. Cardiac resynchronization
therapy (CRT) can reduce the interventricular and intraventricular mechanical
dissynchrony in HF patients. It has been shown that CRT increases the left
ventricular filling time, decreases septal dissynchrony, mitral regurgitation,
and left ventricular volumes allowing a hemodynamic improvement. However, the
development of AF in this setting can avoid the beneficial effects of CRT.
Therefore, this manuscript will review the available data on this topic, the
electrophysiological aspects of AF, to determine what can be done in the event of
an AF complicating congestive HF in CRT patients.
PMID- 28496627
TI - The Phrenic Nerve And Atrial Fibrillation Ablation Procedures.
AB - Radiofrequency ablation is increasingly used as an option to optimally manage
patients with symptomatic atrial fibrillation. Presently, ablationists strive to
improve success rates, particularly with persistent atrial fibrillation, while
simultaneously attempting to reduce complications. A well-recognized complication
with atrial fibrillation ablation is injury to the phrenic nerve giving rise to
diaphragmatic paresis and patient discomfort.Phrenic nerve damage may occur when
performing common components of atrial fibrillation ablation including pulmonary
and superior vena caval isolation. The challenge for ablationists is to
successfully target the arrhythmogenic substrate while avoiding this
complication. In order to do this, a thorough knowledge of phrenic nerve anatomy,
points in the ablation procedure where nerve damage is more likely, and an
understanding of the presently utilized techniques to avoid this complication is
required. In addition, when this complication does arise, prompt recognition of
its occurrence, knowledge of the natural history, and available methods for
management are needed.In this review, we discuss the underlying anatomic
principles, techniques of avoiding phrenic nerve damage, and presently available
methods of diagnosing and managing this complication.
PMID- 28496628
TI - Esophageal Dilatation Post - Gastric Banding And Catheter Ablation For Atrial
Fibrillation: A Case Report.
AB - Esophageal injury is a potential serious complication of catheter ablation for
atrial fibrillation. We report a case of significant esophageal dilatation
following previous laparascopic gastric banding in a patient with permanent
atrial fibrillation undergoing a pulmonary vein isolation procedure.
PMID- 28496625
TI - Atrial Remodeling And Atrial Fibrillation: Mechanistic Interactions And Clinical
Implications.
AB - Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. The
prevalence of AF increases dramatically with age and is seen in as high as 9% of
individuals by the age of 80 years. In high-risk patients, the thromboembolic
stroke risk can be as high as 9% per year and is associated with a 2-fold
increase in mortality. Although the pathophysiological mechanism underlying the
genesis of AF has been the focus of many studies, it remains only partially
understood. Conventional theories focused on the presence of multiple re-entrant
circuits originating in the atria that are asynchronous and conducted at various
velocities through tissues with various refractory periods. Recently, rapidly
firing atrial activity in the muscular sleeves at the pulmonary veins ostia or
inside the pulmonary veins have been described as potential mechanism,. AF
results from a complex interaction between various initiating triggers and
development of abnormal atrial tissue substrate. The development of AF leads to
structural and electrical changes in the atria, a process known as remodeling. To
have effective surgical or catheter ablation of AF good understanding of the
possible mechanism(s) is crucial.Once initiated, AF alters atrial electrical and
structural properties that promote its maintenance and recurrence. The role of
atrial remodeling (AR) in the development and maintenance of AF has been the
subject of many animal and human studies over the past 10-15 years. This review
will discuss the mechanisms of AR, the structural, electrophysiologic, and
neurohormonal changes associated with AR and it is role in initiating and
maintaining AF. We will also discuss briefly the role of inflammation in AR and
AF initiation and maintenance, as well as, the possible therapeutic interventions
to prevent AR, and hence AF, based on the current understanding of the
interaction between AF and AR.
PMID- 28496629
TI - Masquerading Tachycardi.
PMID- 28496630
TI - Evolution of Paroxysmal Atrial Fibrillation to Persistent or Permanent Atrial
Fibrillation: Predictors of Progression.
AB - Introduction: Paroxysmal atrial fibrillation (PAF) eventually progresses to
persistent and permanent AF. The predictors of progression from PAF to persistent
and permanent AF are poorly understood. Methods: Electronic medical records of
437 patients with PAF were reviewed in a retrospective cohort study. Patients
were followed in time and progression to persistent/permanent AF was recorded.
Demographic, clinical and echocardiographic information was collected. A logistic
regression analysis was performed to identify predictors of progression to
persistent/permanent AF. Results: Over a mean duration of 57.3+/-55.9 months,
32.4% of patients progressed to persistent/permanent AF. Mean age of the
population was 67.9+/-13.4 years with 57% males and 92% Caucasian. Univariate
analysis identified higher body higher mass index (BMI), cardiomyopathy,
diabetes, valvular heart disease (VHD), larger left atrial size (LA) and higher
pulmonary artery pressure as predictors of progression. Multivariate logistic
regression analysis larger left atrial size (OR 1.46, CI 1.05-2.04, P 0.002),
cardiomyopathy (OR 2, CI 1.1- 3.3, P 0.003), and moderate to severe valvular
heart disease (OR 3.3, CI 1.4-5, P 0.008) as significant predictors of
progression to persistent/permanent AF. Conclusions: Our study shows that PAF
patients with larger LA, valvular heart disease and cardiomyopathy predict
progression of PAF to persistent/permanent AF. Higher BMI and cardiomyopathy
predicted progression to persistent AF while larger LA size and VHD predicted
progression to permanent AF.
PMID- 28496631
TI - Atrial Fibrillation Ablation: First-Line Therapy?
AB - Background: Ablation for atrial fibrillation (AF) is a widely-accepted treatment
for this arrhythmia. Ablation is traditionally reserved for second-line therapy
in patients who have failed drug therapy, but it may be ready for first-line
treatment. Objective: This article outlines the rationale for using ablation as
first-line therapy for AF. Findings: AF increases both morbidity and mortality.
Unfortunately, drug-based therapy for AF is very ineffective and may contribute
adversely to both patient morbidity and mortality. Ablation addresses the root
causes of AF and thus may be curative. The technique for ablation has become
quite consistent and the outcomes better than those with drug therapy. The
complication risk is also acceptably low. There is even preliminary evidence to
suggest that AF ablation is superior as first-line treatment compared to drugs.
Conclusion: AF ablation is rapidly evolving towards becoming first-line therapy
for some patients with this debilitating arrhythmia.
PMID- 28496632
TI - The Autonomic Nervous System and Atrial Fibrillation:The Roles of Pulmonary Vein
Isolation and Ganglionated Plexi Ablation.
AB - After the sequential successes of catheter ablation for the treatment of pre
excitation syndromes (WPW), junctional reentry (AVNRT) atrial flutter (AFL) and
ventricular arrhythmias, clinical electrophysiologists have focused on the
myocardial basis of atrial fibrillation (AF). Thus, the strategy for ablation of
drug and cardioversion refractory AF was to isolate the myocardial connections
from the focal firing pulmonary veins (PVs) in addition to altering the atrial
substrate maintaining AF. However, the overall success rates have not achieved
those of the other types of ablation procedures. In this review we have
summarized the favorable aspects and drawbacks of pulmonary vein isolation (PVI).
As for the role of the Intrinsic Cardiac Autonomic Nervous System (ICANS), both
basic and clinical evidence has shown that ganglionated plexi (GP) stimulation
promotes initiation and maintenance of AF, and that GP ablation reduces
recurrence of AF following catheter or surgical ablation of these structures.
Based on these findings, the GP Hyperactivity Hypothesis has been proposed to
explain, at least in part, the mechanistic basis for the focal form of AF. For
example, PV isolation may not always be necessary for elimination of AF, as in
the early stages of paroxysmal AF. GP ablation alone, in these cases, may suffice
for focal AF termination. In the persistent and long standing persistent forms
the substrate for AF may be more extensive and therefore require GP ablation plus
PV isolation and/or CFAE ablations. Clinical reports, both catheter based as well
as minimally invasive surgical procedures, which include PVI plus GP ablation
have shown relatively long-term success rates much closer to or equal to those
achieved by myocardial ablation procedures in patients with WPW, AVNRT and AFL.
PMID- 28496634
TI - Laser Ablation Of Atrial Fibrillation: Mid-term Clinical Experience.
AB - Background: Atrial Fibrillation is known to account for one third of all the
strokes caused in the US in the population above the age of 70. Patients treated
with the surgical Cox MAZE operation have been shown to have a 150 fold decrease
in the incidence of stroke over an 18 year period. However, the original Cox MAZE
although extremely successful in treating atrial fibrillation and decreasing the
incidence of strokes was not performed widely because of complexity and
invasiveness of the procedure. A variety of alternative energy based curative
ablation strategies are now available for more minimally invasive therapeutic
management of atrial fibrillation (AF). In this communication, we report our
clinical experience in AF therapy utilizing laser energy ablation technology.
Methods: Fifty two consecutive AF patients underwent concomitant or isolated
ablation prior to any coexisting cardiac procedures that included CABG (coronary
artery bypass surgery, MV (mitral valve) or AV (aortic valve) repairs. All
patients had an epicardially based ablation pattern with basic lesions being en
bloc box type pulmonary vein isolation which included the antral surface of the
left atrium, directed ganglionectomies of the the right anterior and inferior
ganglions, posteriomedial ablation of the IVC ( inferior vena cava), and a right
isthmus ablation. Twenty seven patients had ligation of their left atrial
appendage, 14 patients had resection of the ligament of Marshall, and three
patients had endocardial placed lesions of a mitral annular connecting type
lesion. In order to maintain the patients in normal sinus rhythm (NSR),
electrical cardioversion and anti-arrhythmic drugs were employed as required.
Results: At a median follow-up of 250 days, 44 of the total 52 patients (84.6%)
exhibited NSR.. No complications or mortality were reported due to the laser
procedure. Conclusion: Laser ablation was successfully and safely used for
endocardial and epicardial AF ablation concomitant to other cardiovascular
procedures and in the lone atrial fibrillation treatment utilizing a two port
thoracoscopic approach.
PMID- 28496633
TI - Cost-Effectiveness Of Catheter Ablation Treatment For Patients With Symptomatic
Atrial Fibrillation.
AB - Background: Atrial Fibrillation is the most common cardiac arrhythmia. It
increases the risk of thromboembolic events and many atrial fibrillation patients
suffer quality of life impairment due to disturbed heart rhythm. Pulmonary vein
isolation using radiofrequency catheter ablation treatment is aimed at
maintaining sinus rhythm ultimately improving quality of life. Randomized
clinical trial have shown that catheter ablation is more effective than
antiarrhythmic drugs for the treatment of atrial fibrillation, but its impact on
quality of life and cost-effectiveness has not been widely studied. Aims: To
assess the cost-effectiveness of radiofrequency ablation (RFA) vs. antiarrhythmic
drug (AAD) treatment, among symptomatic atrial fibrillation patients not
previously responding to AAD. Methods: A decision-analytic Markov model was
developed to assess costs and health outcomes in terms of quality adjusted life
years (QALYs) of RFA and AAD over a lifetime time horizon. We conducted a
literature search and used data from several sources as input variables of the
model. One-year rates of atrial fibrillation with RFA and AAD, respe tively, were
available from published randomized clinical trials. Other data sources were
published papers and register data. Results: The RFA treatment strategy was
associated with reduced costs and an incremental gain in QALYs compared to the
AAD treatment strategy. The results were sensitive to whether long-term quality
of life improvement is maintained for the RFA treatment strategy and the risk of
stroke in the different atrial fibrillation health states. Conclusion: This study
shows that the short-term improvement in atrial fibrillation associated with RFA
is likely to lead to long-term quality of life improvement and lower costs
indicating that RFA is cost-effective compared to AAD.
PMID- 28496635
TI - Epicardially Based Pulmonary Vein Isolation for the Treatment of Atrial
Fibrillation Utilizing Laser Energy in the Pig Model.
AB - Purpose: Atrial fibrillation is a common disease that increases the incidence of
cerebrovascular embolic events and cardiac dysfunction. Foci for atrial
fibrillation have been mapped and found to be for the most part located within
the ostia of the pulmonary veins. Since 2002 microwave and radiofrequency energy
sources have been used to create pulmonary vein isolation lesions. This abstract
summarizes the safety and efficacy of performing vein isolation lesions with
laser as the energy source. Description: The large pig model was utilized for
creation of isolation lesions around the pulmonary veins. The Optimaze E360
Surgical Ablation Handpiece from Edwards Lifesciences was utilized, it contains a
4 centimeter diffusing diode laser (980nm). All six of the pig models tolerated
the procedure with a 40-day normal post procedure growth pattern. Evaluation:
Upon reoperation one pig developed ventricular fibrillation with resection of
adhesions. All five remaining pigs were fully tested and demonstrated complete
electrical isolation. Gross pathology revealed intact well defined ablation
lesions with an otherwise completely normal cardiac structure. All lesions were
fully transmural at each histological sectioned point. Conclusions: Laser
technology in the form of the Optimaze E360 Surgical Ablation Handpiece from
Edwards Lifesciences, is able to reliably and consistently produce well defined
electrical isolation scars around the pulmonary veins. This device is also
amenable to performing the isolation procedure using a minimally invasive
approach.
PMID- 28496636
TI - Paroxysmal Lone Atrial Fibrillation Is Associated With An Abnormal Atrial
Substrate: Characterizing The "Second Factor".
PMID- 28496637
TI - Dronedarone For Atrial Fibrillation: Unbridled Enthusiasm Or Just Another Small
Step Forward?
PMID- 28496638
TI - Percutaneous Left Atrial Appendage Exclusion Therapy: Who, Why and How?
AB - Purpose: Patients with atrial fibrillation are at an increased risk of having a
cardio embolic stroke. Stroke is a leading cause of death and disability
worldwide. Current guidelines recommend an antithrombotic regimen to prevent
thromboembolism in medium and high risk patients with AF. However, a substantial
number of patients are not eligible for this therapy. The exclusion of the left
atrial appendage (LAA) from circulation seems to be an alternative strategy for
stroke prevention in AF. This review focuses on the different strategies for LAA
exclusion with special focus on the WATCHMAN Device. Two devices are currently in
use for percutaneous transcatheter occlusion of the LAA: the WATCHMAN(r) - device
and the AMPLATZER(r) -septal occluder. For both devices safety and feasibility
data are available. Additionally about 200 patients received a PLAATO(r) -device-
which is currently no more available due to economic reasons. Patients treated
with the PLAATO device were at high risk for thromboembolic stroke and had
contraindications for oral anticoagulation therapy. The Watchman(r) -device was
implanted in 800 patients that were eligible for long-term anticoagulation
therapy with a moderate risk for thromboembolic stroke due to non-valvular AF.
Summary: For both devices, a reduction in the risk of stroke was documented and
device implantation was shown to be safe and feasible. Provided the ongoing
trials show noninferiority to oral anticoagulation, another therapeutic option
will become available to prevent ischemic strokes.
PMID- 28496639
TI - Pulmonary Vein Isolation using a High Density Mesh Ablator Catheter:
Incorporation of three-Dimensional Navigation and Mappin.
AB - Background: We evaluated the use of a novel High Density Mesh Ablator (HDMA)
catheter in combination with three-dimensional navigation for the treatment of
paroxysmal atrial fibrillation. Methods: The HDMA catheter was used to carry out
pulmonary vein isolation in a consecutive series of patients. Three-dimensional
geometry of the left atrial-pulmonary vein (LA-PV) junctions were first created
with the HDMA catheter. Ostial, proximal and distal sites within the pulmonary
veins were tagged with catheter shadows on the created geometry to allow for re
interrogation of these exact sites after ablation. Results: The HDMA catheter was
successfully used to create three dimensional geometry of the LA-PV junction in a
total of 20 pulmonary veins which involved 5 patients. In all cases, ostial
ablation alone was sufficient to achieve electrical isolation. No significant
pulmonary vein stenosis was seen acutely after ablation. Conclusion: We describe
the successful use of the novel HDMA catheter to create three-dimensional
geometry of the LA-PV junction to assist with pulmonary vein isolation.
PMID- 28496640
TI - Review of Dominant Frequency Analysis in Atrial Fibrillation.
AB - Significant advancements have been made in the technology and approach to
catheter ablation of atrial fibrillation (AF). Pulmonary vein isolation has
emerged as the dominant strategy in this procedure and has fueled innovations in
catheter design as well as various mapping and navigation systems. Mapping and
targeting of complex fractionated atrial electrograms has also emerged as an
additional or alternate strategy employed by some ablationists. Recently,
attention is being drawn to a new approach targeting atrial sites with high
dominant frequencies (DF) derived from their electrograms. This article is a
review of the basic concepts of DF, the relevant literature behind DF analysis in
AF, and the potential clinical applicability of DF analysis for catheter
ablation.
PMID- 28496641
TI - Atrial Fibrillation in Hypertrophic Obstructive Cardiomyopathy - Antiarrhythmics,
Ablation and More!
AB - Hypertrophic cardiomyopathy (HCM) is a genetic disease of the cardiac sarcomere
with an autosomal dominant pattern of inheritance. Patients with HCM are at high
risk of developing atrial fibrillation (AF) particularly in the setting of
advanced diastolic dysfunction and left atrial enlargement. AF is a marker of
increased mortality and morbidity and results in a significant reduction in
quality of life. Antiarrhythmic medications improve symptoms and reduce AF
recurrence, but few are safe and there exists little data to guide their long
term use in HCM. Non-pharmacologic approaches have emerged and have equal or
greater efficacy than pharmacologic approaches. Although these approaches are
promising, the long-term impact on atrial function needs to be carefully studied
as it may impact quality of life in patients that age in the setting of a
progressive diastolic disease disorder. Nonetheless, with the significant impact
of AF in HCM, rhythm control strategies are often required. The understanding of
rhythm control strategies in HCM, an often rapidly progressive diastolic
dysfunction disorder, may provide insight in how to treat the much more prevalent
AF patient with hypertensive cardiomyopathy. Regardless of treatment strategy
(rhythm or rate control) patients are a moderate to high risk of thromboembolism
and until data are available to suggest otherwise require long-term warfarin
anticoagulation.
PMID- 28496642
TI - Role of Inflammation in Early AF Recurrence After PV Isolation.
PMID- 28496643
TI - The Role of Intracardiac Echocardiography in Atrial Fibrillation Ablation.
AB - Radiofrequency catheter ablation of pulmonary veins has emerged as an effective
therapy for patients with symptomatic atrial fibrillation. Advances in real-time
intracardiac echocardiography with 2D and Doppler color flow imaging have led to
it integration in atrial fibrillation ablation procedures. It allows imaging of
the left atrium and pulmonary veins, including identification of anatomic
variations. It has an important role in guiding transseptal catheterization,
imaging the pulmonary vein ostia, assisting in accurate placement of mapping and
ablation catheters, monitoring lesion morphology and flow changes in the ablated
pulmonary veins, hence allowing titration of energy delivery. Importantly, it
allows instant detection of procedural complications.
PMID- 28496644
TI - Management of the Asymptomatic Patient After Catheter Ablation of Atrial
Fibrillation.
AB - Ablative therapy for atrial fibrillation is becoming more commonplace, and some
minimally symptomatic or asymptomatic patients will be referred for ablative
therapy. Reasons to ablate asymptomatic patients include young age and/or the
presence of a tachycardia induced cardiomyopathy; in addition, some symptomatic
patients may become asymptomatic after ablation. Managing these patients can be
challenging. In this review, we will discuss the use of telemetric monitoring,
antiarrhythmic drugs and anticoagulation after ablation in asymptomatic patients
with atrial fibrillation.
PMID- 28496645
TI - C-Reactive Protein and The Risk of Atrial Fibrillation: A Systematic Review and
Meta-Analysis.
AB - There is increasing evidence linking C-reactive protein (CRP) and atrial
fibrillation (AF). Despite the abundance of literature, confusion exists
regarding this association because of inconsistent results. MEDLINE and Cochrane
Controlled Trials Register databases were carefully searched through July, 2009
combining the following terms "C-reactive protein" and "atrial fibrillation".
Reference lists of selected articles and reviews were also screened to identify
additional relevant studies. Of the 129 studies initially identified, 8 studies
with 7507 subjects (719 with AF) were included in the meta-analysis. Analysis
yielded a relative risk of 1.63 (1.43, 1.86) for occurrence of AF when CRP level
was above a cut off of 3-3.5 mg/l. When 3 studies with data on a higher cut off
of 4.5-5.0 mg/l were analyzed separately, the relative risk was 4.03 (3.1, 5.25).
Our study suggests that elevated CRP is associated with increased risk for AF.
The risk appears incremental with higher CRP levels conferring proportionately
increased risk. There is an urgent need for further large scale, well designed
prospective studies to assess the relationship between CRP and AF.
PMID- 28496646
TI - Level Of Natriuretic Peptide Determines Outcome In Atrial Fibrillation.
AB - : Background: Natriuretic peptide (NP) is high in atrial fibrillation (AF) and
may decrease after cardioversion to sinus rhythm and the levels of atrial NP
(ANP) and brain NP (BNP) in different types of AF and whether ANP and BNP have
predictive values for relapsed AF have not been determined. Purpose: We aimed to
examine the levels of ANP and BNP in AF to determine their roles in different
types of AF, including a predictive value in relapsed AF. Methods and Results:
ANP and BNP were measured in 100 consecutive patients with AF and without heart
dysfunction at baseline and in 20 controls. All patients had higher levels than
controls (p<0.01). After cardioversion treatment with antiarrhythmic therapy, 40
patients failed to cardioversion successfully and still showed AF, whereas 60
patients were successful. ANP and BNP levels decreased significantly after
cardioversion (163.55+/-54.27pg/ml vs. 200.20+/-55.63 pg/ml; 124.15+/-43.00 pg/ml
vs. 161.99+/-48.04 pg/ml, for ANP and BNP respectively, both p<0.0001). 18 of the
60 successfully cardioverted patients had AF recurred within 24 hours, who were
then excluded from 500-day follow-up and the remaining 42 patients were enrolled.
During 500-day follow-up period, AF relapsed in 16 patients. Comparing with the
42 patients, the 16 patients showed higher concentrations of ANP (187.72+/-32.79
pg/ml vs. 138.42+/-30.65 pg/ml, p<0.0001). Besides, both ANP and BNP were
significantly higher in the relapsed patients than those remained SR during
follow-up (153.38+/-29.61pg/ml vs. 129.21+/-27.98pg/ml for ANP, p=0.01 and
147.41+/-25.95pg/ml vs. 121.87+/-20.53pg/ml for BNP, p=0.001). The area under the
receiver-operating characteristic curve was 0.799 for BNP and 0.706 for ANP in
predicting a relapse of AF. Using the BNP optimized cut-off level of 138 pg/ml,
relapsed AF can be predicted with relatively acceptable accuracy. CONCLUSIONS:
ANP and BNP decrease significantly after cardioversion in patients with AF, and
both can be useful predictors of relapsed AF.
PMID- 28496647
TI - Monomorphic Outflow Tract Ventricular Tachycardia: Unique Presenting
Manifestation of Gitelman's Syndrome.
PMID- 28496648
TI - Dabigatran, A Direct Thrombin Inhibitor, In Atrial Fibrillation: Is It Already
Time For A Change In Oral Anticoagulation Therapy?
PMID- 28496649
TI - Effect of Statins in Preventing Postoperative Atrial Fibrillation Following
Cardiac Surgery.
AB - Background: Postoperative occurrence of AF has been associated with less
favorable outcomes in patients undergoing cardiac surgery and may result in
increased postoperative morbidity and mortality. Objectives: A focused clinical
question was designed and a Meta-analysis of published studies was performed to
identify the effect of preoperative use of statins on the occurrence of AF after
cardiac surgery. Methods: Using the Medline database, the Cochrane clinical
trials database and online clinical trial databases, we reviewed all RCTs and
observational studies examining the effect of statins on AF occurrence following
cardiac surgery. We searched for literature published before April 2009 and
earlier. Results: This analysis identified 6 studies (observational studies)
which examined the effect of preoperative use of statins on AF occurrence
following cardiac surgery, involving 10165 patients. Contradictory to most of
previous studies, the overall outcomes suggested that the statins group did not
have a significant decrease in AF occurrence following cardiac surgery comparing
to control group (P = 0.19). Conclusions: The preoperative medication of statins
showed no significant decrease in AF occurrence following cardiac surgery in this
Meta-analysis result. More prospective studies and researches are needed to
explore and demonstrate the accurate mechanism and effect of statins on
postoperative AF.
PMID- 28496650
TI - Current Perspectives: Rheumatic Atrial Fibrillation.
PMID- 28496651
TI - Atrial Fibrillation in Athletes - The Story Behind The Running Hearts.
PMID- 28496653
TI - Determining Esophageal Anatomy With A New Electroanatomical Mapping System.
PMID- 28496652
TI - An Update on the Energy Sources and Catheter Technology for the Ablation of
Atrial Fibrillation.
AB - The ablation of atrial fibrillation (AF) is an area of intense research in
cardiac electrophysiology. In this review, we discuss the development of catheter
based interventions for AF ablation. We outline the pathophysiologic and anatomic
bases for ablative lesion sets and the evolution of various catheter designs for
the delivery of radiofrequency (RF), cryothermal, and other ablative energy
sources. The strengths and weaknesses of various specialized RF catheters and
alternative energy systems are delineated, with respect to efficacy and patient
safety.
PMID- 28496654
TI - The Utility of Ambulatory Electrocardiographic Monitoring for Detecting Silent
Arrhythmias and Clarifying Symptom Mechanism in an Urban Elderly Population with
Heart Failure and Hypertension: Clinical Implications.
AB - Background: Atrial and ventriclar tachyarrhythmias, as well as bradyarrhythmias,
in the elderly with heart failure (HF) and/or hypertension (HTN) have been well
documented. However, the frequency of these arrhythmias, whether silent or
symptomatic, and their association with subsequent cardiac events has not been
well defi ned in patients 65 years or older with HF and other cardiovascular risk
factors. Objective: To assess the value of 2 weeks of remote, transtelephonic
cardiac monitoring for detecting arrhythmias in an elderly, urban population
living with HF. Methods: Fi" y-four patients with a history of systolic HF and/or
HTN were consented and enrolled. All wore an auto triggered cardiac loop monitor
for 2 weeks that captures EKG data and both silent and symptomatic arrhythmias
were recorded. Results: Mean age was 73 +/- 6 years with 59% of subjects were
females, 74% Hispanic, 22% black, and 4% white/other. All patients had HF and 94%
had HTN. From the cardiac monitoring, 72% demonstrated ectopic atrial and
ventricular activity, and 1 paroxysmal episode of atrial fi brillation was
documented. In addition, 3 subjects had signifi cant non-sustained ventricular
tachycardia, and 4 individuals had severe bradycardia recorded on cardiac
monitoring. These 7 individuals underwent placement of an implantable
cardioverter defi brillator (ICD) or pacemaker based on the documented
arrhythmias which may have otherwise gone undetected. Conclusions: A substantial
proportion of patients exhibited cardiac arrhythmias. Future morbidity was
prevented because of the detection of arrhythmias on monitoring that led to
specifi c therapies such as pacemaker or ICD implantation which otherwise may not
have been implemented.
PMID- 28496655
TI - Electrophysiological Changes of the Atrium in Patients with Lone Paroxysmal
Atrial Fibrillation.
AB - Introduction: Paroxysmal atrial fibrillation (PAF) is a common arrhythmia, and it
is associated with various cardiac conditions. On the other hand, lone PAF has no
identifiable underlying cause, and can occur any time for no apparent reason. The
underlying causes may modify the electrophysiological properties of the atrium in
different ways and extent. However this setting may be different in patients with
lone PAF. We sought to investigate the atrial electrophysiological properties in
lone PAF. Material and Methods: This study included 62 control subjects (Control
group) and 58 patients with lone PAF (LAF group). The following atrial
vulnerability parameters induced by programmed atrial stimulation were assessed
and quantitatively measured: 1) the atrial effective refractory period (ERP), 2)
the atrial conduction delay (CD) zone, and 3) the maximum CD. Results: The mean
atrial ERP of the Control group was 215+/-29 ms, and that of LAF group was 208+/
28 ms, p<0.05. The mean atrial CD zone of the LAF group was (50+/-28 ms)
significantly greater than that of controls (34+/-22 ms) (p<0.01). The mean
maximum CD of the LAF group (62+/-29 ms) was also significantly greater than that
of controls (43+/-20 ms) (p<0.01). Conclusions : There is a greater conduction
delay of the atrium and shorter refractoriness in patients with lone PAF.
Patients without underlying causes for the development of PAF exhibit
abnormalities in the electrophysiological properties of the atrium.
PMID- 28496657
TI - Is Isolation of Arrhythmogenic Pulmonary Veins Sufficient for the Long-term
Efficacy of Atrial Fibrillation Ablation?
PMID- 28496656
TI - Lone AF - Etiologic Factors and Genetic Insights into Pathophysiolgy.
AB - Ever since atrial fibrillation (AF) was first recognized in young people (so
called "lone" AF) over 4 decades ago, there has been increasing focus on
determining the underlying pathophysiology of the condition. Although lone AF is
presumed to be a highly heterogeneous disease, recent studies have identified
novel risk factors such as inflammation, oxidative stress, endurance sports and
genetics, for the arrhythmia. This monograph aims to highlight some of the recent
advances in our understanding of the molecular pathophysiology of lone AF
especially insight provided by contemporary genetic studies. These insights may
provide novel therapeutic targets for treatment of this challenging arrhythmia in
young patients.
PMID- 28496658
TI - AF Termination: the Holy Grail of Persistent AF Ablation?
PMID- 28496659
TI - Atrial Fibrillation Susceptibility Alleles on Chromosome 4q25 Modulate Response
to Catheter Ablation.
PMID- 28496661
TI - Use of Ivabradine in Postural Orthostatic Tachycardia Syndrome.
AB - Postural orthostatic tachycardia syndrome (POTS) is characterized by
inappropriate increase in heart rate on assuming upright position from a supine
position without a necessary drop in blood pressure. Etiology of this condition
is complex and multifactorial. Autonomic dysfunction,[1] hypovolemia,[2] hyper
responsiveness of beta adrenergic receptors[3] with associated elevations of
plasma norepinephrine levels have been implicated as underlying pathophysiologic
mechanisms. Beta blockers have previously been used to treat this condition.
Ivabradine which selectively inhibits If ion current in the sino atrial node, has
been reported to be useful in patients with POTS.[4,5] We present one further
such case of POTS successfully treated by Ivabradine.
PMID- 28496660
TI - Electrophysiological Changes of the Atrium in Patients with Lone Paroxysmal
Atrial Fibrillation.
AB - BACKGROUND: The "Pill-in-Pocket" (PIP) is an approach to atrial fibrillation (AF)
where oral anti-arrhythmics at 75% to 100% of the normal daily dose, given as a
single dose, is used to convert recent-onset AF. Pro-arrhythmic risk has limited
this approach to patients without structural heart disease (SHD). Ranolazine is
an anti-anginal agent, which inhibits the abnormal late Na+ channel current
resulting in decreased Na+/Ca++ overload. This inhibits after-depolarizations and
reduces pulmonary vein firing, which have been implicated in the initiation and
propagation of AF. Ranolazine increases atrial refractoriness and has no known
pro-arrhythmic affects. Ranolazine is routinely given to patients with SHD. The
ability of Ranolazine to terminate AF in man has not been described but if useful
could be a safer PIP agent with application in the presence or absence of SHD. We
describe our experience using oral Ranolazine to convert new or recurrent AF.
METHOD: 2000 mg of ranolazine was administered to 35 patients with new (16
patients) or recurrent (19 patients) AF of at least 3 but not greater than 48
hours duration. Clinical features, echocardiographic data, and SHD were noted.
Success was defined as restoring sinus rhythm within 6 hours of Ranolazine.
RESULTS: All but 4 patients had some form of SHD. Twenty-five patients were in
the hospital, 5 were in the office, and 5 were at home at the time Ranolazine was
administered. Twenty-five of 35 patients converted to sinus rhythm. No pro
arrhythmic effects, hemodynamic instability, adverse rate effects, or perceived
intolerance were noted. The 71% conversion rate was comparable to other reported
PIP protocols and much higher than reported placebo conversion rates.
CONCLUSIONS: High dose oral Ranolazine shows utility as a possible safe agent to
convert new or recurrent AF. Larger placebo-controlled studies would appear to be
warranted.
PMID- 28496662
TI - Invasive Management of Atrial Fibrillation and the Elderly.
PMID- 28496663
TI - Is AF Ablation Cost Effective?
AB - The use of catheter ablation to treat AF is increasing rapidly, but there is
presently an incomplete understanding of its cost-effectiveness. AF ablation
procedures involve significant up-front expenditures, but multiple randomized
trials have demonstrated that ablation is more effective than antiarrhythmic
drugs at maintaining sinus rhythm in a second-line and possibly first-line rhythm
control setting. Although truly long-term data are limited, ablation, as compared
with antiarrrhythmic drugs, also appears associated with improved symptoms and
quality of life and a reduction in downstream hospitalization and other health
care resource utilization. Several groups have developed cost effectiveness
models comparing AF ablation primarily to antiarrhythmic drugs and the model
results suggest that ablation likely falls within the range generally accepted as
cost-effective in developed nations. This paper will review available information
on the cost-effectiveness of catheter ablation for the treatment of atrial
fibrillation, and discuss continued areas of uncertainty where further research
is required.
PMID- 28496664
TI - Ranolazine for Atrial Fibrillation: Too Good to be True?
PMID- 28496665
TI - Commentary on : New-Onset Atrial Fibrillation Predicts Long-Term Mortality After
Coronary Artery Bypass Graft by El-chami et.al.
PMID- 28496666
TI - Supraventricular Ectopic Activity: When Excessive it is not all Benign!
PMID- 28496667
TI - Stroke Prevention in Atrial Fibrillation.
AB - Non-valvular atrial fibrillation is a common and from a neurological perspective
the most significant cardiac arrhythmia with a growing world-wide incidence. It
also carries a significant associated morbidity and mortality, with cardioembolic
strokes arguably being the most disabling sequelae. This brief review will
highlight the important studies and the latest treatment modalities available for
stroke prevention in patients with non-valvular atrial fibrillation.
PMID- 28496668
TI - Endurance Sport Practice and Atrial Fibrillation.
PMID- 28496669
TI - Effect of High-dose Telmisartan on the Prevention of Recurrent Atrial
Fibrillation in Hypertensive Patients.
AB - Background: Telmisartan has been shown to exert an equivalent action as ramipril
on the prevention of cardiovascular events, but the dose-dependent actions of
telmisartan on the prevention of events remain unknown. Objective: We
investigated the dose-dependent effects of telmisartan on the prevention of AF in
patients associated with risk factors. Methods: One hundred hypertensive patients
were randomized to take 40 mg (low-dose group: n=57) or 80 mg (high-dose group:
n=43) of telmisartan for 24 months. The primary endpoints were defined as a new
development and/or recurrence of atrial fibrillation (AF). Results: The mean
values of the blood pressure in both groups decreased significantly and to
similar degrees after 24 months, in the low-dose (p < 0.01) and high-dose (p <
0.01) groups. At the end of the follow-up, the incidence of AF was lower in the
high-dose group than in the low-dose group (p < 0.05). Moreover, the proportion
of AF recurrences in the patients with a past history of paroxysmal AF was lower
in the high-dose group than in the low-dose group (p < 0.05). Further, using a
logistic regression model, there were no risk factors associated with the
incidence of AF. Conclusion: The results indicated that telmisartan in low doses
was as effective in controlling the blood pressure as in high doses, but high
doses of telmisartan had beneficial effects on preventing the recurrence of AF in
hypertensive patients.
PMID- 28496670
TI - Atrial Tachycardias Occurring After Atrial Fibrillation Ablation: Strategies for
Mapping and Ablation.
AB - The occurrence of left atrial tachycardias (AT) after catheter ablation for
atrial fibrillation (AF) is common, especially after more extensive ablation of
persistent AF. These AT are invariably symptomatic and often do not respond to
medical therapy. The initial strategy involves ventricular rate control,
cardioversion, and observation as some tachycardias may resolve with time. For
persistent ATs, effective management frequently requires catheter intervention.
Careful characterization of the tachycardia mechanism is essential in designing
an effective ablation strategy that would also avoid further creation of pro
arrhythmic substrate. With this review, we summarize the incidence, mechanism,
diagnosis and treatment of ATs occurring after AF ablation.
PMID- 28496672
TI - The Power of One: a Highly Detailed, Log-Based, Case Example that Clearly
Demonstrates the Effective Use of Ranolazine for the Control of Progressive
Atrial Fibrillationn.
PMID- 28496671
TI - Management of Atrial Fibrillation in Pregnancy.
AB - Pregnancy is accompanied by a variety of cardiovascular changes in normal women;
all of these changes are thought to promote arrhythmogenesis. Atrial fibrillation
is unusual during pregnancy and it can represent a benign, self-limited lone
atrial fibrillation or can be hemodynamically significant in parturient with or
without structural heart disease. Management of atrial fibrillation should be the
same as in non-pregnant women, but requires faster intervention, even in patients
with a normal heart function, and cautious use of medication to avoid harm to the
fetus. We might remember that synchronized electrical cardioversion has been
performed safely during all stages of pregnancy.
PMID- 28496673
TI - Angiotensin Receptor Blockers for the Prevention of Atrial Fibrillation
Recurrences: Unending Hot Debate.
PMID- 28496674
TI - Left Atrial Appendage: Extending the Search for New Sources of Atrial
Fibrillation Triggers.
PMID- 28496675
TI - Commentary on: Pericardial Fat is Independently Associated with Human Atrial
Fibrillation by Al Chekakie et al.
PMID- 28496676
TI - Ablation of Longstanding Persistent Atrial Fibrillation.
PMID- 28496677
TI - Reducing Ionizing Radiation Associated with Atrial Fibrillation Ablation: An
Ultrasound-Guided Approach.
AB - Radiation exposure with cardiac interventional procedures is an emerging concern.
Patients receiving radiofrequency ablation for atrial fibrillation (AF) still
routinely undergo pre-ablation computed tomography (CT) scans for definition of
left atrial and pulmonary vein anatomy, as well as creation of a surrogate
geometry. In an effort to decrease ionizing radiation associated with AF
ablation, an ultrasound-guided surrogate geometry approach is proposed as an
alternative to routine CT imaging. Ten patients underwent AF ablation using
intracardiac ultrasound for the creation of a surrogate left atrial geometry
(CartoSound, Biosense Webster, CA); and ten control-cases who had conventional CT
guided imaging (CartoMerge, Biosense Webster, CA) were matched for age, gender,
and type of catheter ablation. Sources of radiation included 1) intraprocedural
fluoroscopy (CartoSound: 151 +/- 43 mGray*cm^2, CartoMerge: 174 +/- 130
mGray*cm^2; p=0.6) and 2) CT ionizing radiation (CartoSound: 0 mSv, CartoMerge
9.4 +/- 2.3 mSv/CT scan.) When comparing clinical success rates after a trial of
previously ineffective anti-arrhythmic drugs, ultrasound-guided AF ablation was
non-inferior to a CT-guided approach. This potentially obviates the need for CT
guided imaging, therefore reducing doses of ionizing radiation by nearly 10 mSv
per AF catheter ablation.
PMID- 28496678
TI - The Use of Cryoballoon Ablation in Atrial Fibrillation: Simplifying Pulmonary
Vein Isolation?
AB - Atrial fibrillation (AF) is certainly the most common arrhythmia encountered in
clinical practice, reaching epidemic proportions in occidental society. Nowadays,
transcatheter ablation using radiofrequency (RF) has become a popular technique
in the treatment of drug-resistant AF. Since ectopic beats originating from the
pulmonary veins (PVs) have been shown to be the main trigger initiating AF,
electrical isolation of these venous structures has become the goal when
performing this procedure.
PMID- 28496679
TI - Gender and Racial Characteristics of Patients Referred to a Tertiary Atrial
Fibrillation Center.
AB - Atrial Fibrillation Centers (AFCs) are becoming increasingly common and are often
developed at institutions to provide comprehensive evaluation and management for
patients with atrial fibrillation (AF) including catheter and surgical ablation.
Studies have shown that women and racial minority patients are less likely to be
offered aggressive or invasive therapies. The University of Virginia (UVA) AFC
was opened in 2004. We analyzed data collected during initial visits to our AFC
from 2004-2008 to determine the gender and racial characteristics of a tertiary
AFC population. Multivariable regression analysis was used to compare clinical
characteristics. There were a total of 1664 consecutive initial patient visits.
Cardiologists referred 61% and primary care physicians referred 37% of patients.
Twice as many men were referred as women (570 vs. 1094; P<0.0001). Women were
older (68.0+/-11.9 vs. 62.4+/-13.0 years; P<0.0001) and more symptomatic with
palpitations (80% vs. 73%; P=0.008), but otherwise were not substantially
different from men. Our referring physicians treated the majority of both men and
women with anticoagulant and rate-controlling medications. African American
patients accounted for 2.8% of AFC initial visits. In contrast, they accounted
for 7.4% of patients seen for a primary diagnosis of AF at all other UVA
outpatient clinics (P<0.0001). In conclusion, the demographics of a tertiary AFC
are different than those of the general population. Women and racial minority
patients are underrepresented, and the women have few comorbidities and symptoms
than the known epidemiology would lead us to expect.
PMID- 28496680
TI - Anticoagulation after Atrial Fibrillation Ablation: Many Blanks to Fill.
AB - Long-term maintenance of sinus rhythm (SR) after catheter ablation of atrial
fibrillation (AF) has remained an open issue awaiting further relevant data. It
is of paramount importance as our everyday decisions on discontinuing
anticoagulation after ablation rest on the belief in the absence of clinically
significant asymptomatic AF episodes and constant SR for the rest of the
patient's life. Both aspects are difficult to ascertain, for the tools of truly
continuous ECG monitoring are not comfortably applicable, and routine follow-up
tends to thin out beyond 1 year in asymptomatic patients without apparent
arrhythmia recurrences.
PMID- 28496681
TI - Atrail Fibrillation after Carfiac Surgery: Benign or Deserving of Prophylaxis.
AB - New onset atrial fibrillation (AF) is the commonest complication after cardiac
surgery affecting around 30% of coronary artery bypass graft (CABG) patients, up
to 50% of valve surgery patients and as many as 60% of those undergoing combined
valve and CABG operations. After cardiac transplantation where the native
pulmonary veins are electrically separated from the donor heart atria the
incidence is only 11%.
PMID- 28496682
TI - Left Atrial Volume and Post-Operative Atrial Fibrillation after Aortic Valve
Replacement.
AB - Post-operative atrial fibrillation (POAF) after valve surgery is associated with
increased morbidity and mortality. Risk factors identified in the past to predict
POAF are of moderate accuracy. We performed a retrospective analysis of 139
patients undergoing aortic valve replacement for aortic stenosis. Post-operative
AF occurred in 44% of the patients. In multivariate analysis only left atrial
volume (LAV) index was a predictor of POAF. A LAV index of >46 cc/m2 predicted
POAF with a sensitivity and specificity of 92% and 77%. We propose that LAV index
can be used preoperatively to identify patients at risk for POAF to target
preventive interventions. Background: Post-operative atrial fibrillation (POAF)
is common after valve surgery and is associated with increased morbidity and
mortality. Many of the previously identified predictors of POAF are of moderate
accuracy. Left atrial volume (LAV) index has been proposed in the past as a
predictor of POAF in patients undergoing cardiac surgery. In patients with aortic
stenosis (AS), increased LAV is a marker of severity of stenosis. Hypothesis:
Left atrial volume index is a very good predictor of POAF in patients undergoing
aortic valve replacement (AVR) for AS. Methods: We performed a retrospective
analysis of 139 consecutive patients with no previous atrial fibrillation (AF)
undergoing AVR for AS in our center. Results: Post-operative AF occurred in 44%
of patients. Patients with POAF had a longer hospital stay compared to patients
without (12 vs 8 days; p < 0.001). In univariate analysis, age (p = 0.046),
aortic valve area (p = 0.005) and LAV index (p < 0.001) were significant
predictors of POAF. In multivariate analysis only LAV index (R2= 0.58; p < 0.001)
predicted POAF. A LAV index > 46ml/m2 predicted POAF with a sensitivity and
specificity of 92% and 77% respectively. Moreover, there was a significant
increase in the incidence of POAF with increasing quartiles of LAV index,
supporting causality. Conclusion: Left atrial volume index is an excellent
predictor of POAF in patients undergoing AVR for AS. It can be used for selecting
patients who are at a high risk for developing POAF to target preventive
interventions.
PMID- 28496683
TI - Atrial Tachycardia Successfully Ablated from the Left Coronary Sinus Cusp of the
Aorta: An Unusual Site of Origin.
AB - It has been recognized in the last decade that atrial and ventricular
tachycardias may arise from the myocardium around the aorta. These tachycardias
can be ablated from the coronary sinus cusps of the aorta (ASCs) . In some of
those tachycardias, the site of origin may be epicardial and thus can be ablated
only through the thin structure of the ASCs. It is important to know how to make
a diagnosis, map and ablate tachycardias arising from this region.
PMID- 28496684
TI - Cardiac Image Registration: Rotational Error Correction and Gated Stabilization
for Cardiac Motion.
AB - Background: Dynamic motion of the heart due to cardiac and respiratory cycles,
and rotation from varying patient positions between imaging modalities, can cause
errors during cardiac image registration. This study used phantom, patient and
animal models to assess and correct these errors. Methods and Results: Rotational
errors were identified and corrected using different phantom orientations. ECG
gated fluoro images were aligned with similarly gated CT images in 9 patients,
and accuracy assessed during atrial fibrillation (AF) and sinus rhythm. A
tracking algorithm corrected errors due to respiration; 4 independent observers
compared 25 respiration sequences to an automated method. Following correction of
these errors, target registration error was assessed. At 20 mm and 30 mm from the
phantom model's center point with an in-plane rotation of 8 degrees, measured
error was 2.94 mm and 5.60 mm, respectively, and the main error identified. A
priori method accurately predicted ECG location in only 38% (p=0.0003) of 313 R-R
intervals in AF. A posteriori method accurately gated the ECG during AF and sinus
rhythm in 97% and 98% of 375 beats evaluated, respectively (p=NS). Tracking
algorithm for ECG-gated motion compensation was identified as good or fair 96% of
the time, with no difference between observers and automated method (chi
square=25; p=NS). Target registration error in phantom and animal models was
1.75+/-1.03 mm and 0 to 0.5 mm, respectively. Conclusions: Errors during cardiac
image registration can be identified and corrected. Cardiac image stabilization
can be achieved using ECG gating and respiration.
PMID- 28496685
TI - Role of Remote Navigation Systems in AF Ablation.
AB - During the past decade atrial fibrillation (AF) ablation has developed from being
an experimental treatment option to an evidence based therapy implemented in
current guidelines.[1-2] Irrigated radiofrequency current guided ablations remain
the golden standard of pulmonary vein isolation (PVI) procedures. Although
practiced more frequently, it remains a demanding procedure requiring skilful
operators. Novel technologies such as balloon based catheters or remote
navigation (RN) systems have been developed to overcome the pitfalls of manual
ablation procedures.
PMID- 28496686
TI - The Cost of Thromboembolic Events and their Prevention among Patients with Atrial
Fibrillation.
AB - Aim: Atrial fibrillation (AF) is the most common type of cardiac arrhythmia.
People with AF have a significantly increased risk of thromboembolic events,
including stroke, and the main treatment is therefore aimed at preventing
thromboembolic events via anticoagulation with warfarin or acetylsalicylic acid.
However, the development of new anticoagulation treatments has prompted a need to
know the current cost of AF-related thromboembolic events, for future cost
effectiveness comparisons with the existing treatments. In this study, we
estimated the cost of thromboembolic events and their prevention among Swedish AF
patients in 2010. Methods: The relevant costs were identified, quantified, and
valued. The complications included were ischaemic and haemorrhagic stroke,
gastrointestinal bleeding, and other types of major bleeding caused by AF.
Treatments intended to lower the risk of ischaemic stroke were also included. A
societal perspective was used, including productivity loss due to morbidity.
Patients with a CHADS2 score of 1 or higher were included. Results: Among the 9
340 682 inhabitants of Sweden, there are 118 000 patients with AF and at least
one more risk factor for stroke, comprising 1.26% of the population. Of these
patients, 43.3% are treated with warfarin, 28.3% use acetylsalicylic acid, and
28.3% are assumed to have no anticoagulation treatment. The cost of AF-related
complications and its prevention in Sweden was estimated at ?437 million for
2010, corresponding to ?3 712 per AF patient per year. The highest cost was
caused by stroke, and the second highest by the cost of monitoring the warfarin
treatment. As the prevalence of AF is expected to increase in the future, AF
related costs are also expected to rise. Conclusion: Thromboembolic events cause
high costs. New, easily-administered treatments that could reduce the risk of
stroke have the potential to be cost-effective.
PMID- 28496687
TI - Septic Shock due to Implantable Cardiac Defibrillator Related Infection.
AB - Infection is an important complication of cardiac device implantation. We report
the case of a 61 year old patient presenting with septic shock caused by cardiac
device infection (CDI) three-weeks after device implantation. At initial
presentation, there was an absence of both localising signs and echocardiographic
evidence of CDI. Later, Staphylococcus aureus was cultured from blood and the pre
pectoral pocket. 48 hours after admission the device and leads were explanted in
theatre by simple traction. Despite appropriate antibiotics and full supportive
care (including haemofiltration, ventilation and inotropic support), the patient
died on day six. Cardiac device infection may present with septic shock in the
absence of localising features. A high index of suspicion is required,
particularly for early CDI.
PMID- 28496688
TI - Atrial Fibrillation in the Wolff-Parkinson-White Syndrome.
AB - Since the advent of catheter ablation for atrial fibrillation (AF) aiming the
pulmonary veins a few years ago, there has been an overwhelming interest and a
dramatic increase in AF investigation. AF has a different dimension in the
context of the Wolff-Parkinson-White (WPW) syndrome. Indeed, AF may be a
nightmare in a young person that has an accessory pathway (AP) with fast
anterograde conduction. It may be life-threatening if an extremely rapid
ventricular response develops degenerating into ventricular fibrillation.
Therefore, it is very important to know the mechanisms involved in the
development of AF in the WPW syndrome. There are several possible mechanisms that
may be involved in the development of AF in the WPW syndrome, namely, spontaneous
degeneration of atrioventricular reciprocating tachycardia into AF, the
electrophysiological properties of the AP, the effects of AP on atrial
architecture, and intrinsic atrial muscle vulnerability. Focal activity, multiple
reentrant wavelets, and macroreentry have all been implicated in AF, perhaps
under the further influence of the autonomic nervous system. AF can also be
initiated by ectopic beats originating from the pulmonary veins, and elsewhere.
Several studies demonstrated a decrease incidence of AF after successful
elimination of the AP, suggesting that the AP itself may play an important role
in the initiation of AF. However, since AF still occurs in some patients with the
WPW syndrome even after successful ablation of the AP, there should be other
mechanisms responsible for the development of AF in the WPW syndrome. There is a
clear evidence of an underlying atrial muscle disease in patients with the WPW
syndrome. Atrial myocardial vulnerability has been studied performing an atrial
endocardial catheter mapping during sinus rhythm, and analizing the recorded
abnormal atrial electrograms. This review analizes the available data on this
singular setting since AF has a reserved prognostic significance in patients with
the WPW syndrome, and has an unusually high incidence in the absence of any
clinical evidence of organic heart disease.
PMID- 28496689
TI - Computed Tomography Imaging in Atrial Fibrillation Ablation.
AB - Atrial fibrillation (AF) is the most common supraventricular arrhythmia in adults
and catheter ablation has increasingly become the therapy of choice for
symptomatic, recurrent, drug refractory AF. The purpose of this review is to
evaluate the utility of computed tomography (CT) imaging in guiding
radiofrequency catheter ablation (RFCA), as well as highlight the additional
radiographic and functional anatomic data provided by CT in comparison to
alternative radiographic modalities.
PMID- 28496690
TI - Preoperative Statin use is not Associated with a Reduced Risk of Atrial
Fibrillation After Cardiac Surgery.
AB - Introduction: Postoperative atrial fibrillation (POAF) is prevalent after cardiac
surgery and associated with significant morbidity and costs. Statins are commonly
used in this population and may be a preventative strategy for PAOF. We wished to
examine the effect of preoperative statin use on the risk of POAF after cardiac
surgery. Methods: A retrospective, observational study was conducted using data
from 489 adult patients who underwent cardiac surgery at a single institution.
Univariate analyses and unconditional logistic regression were used to determine
the impact of preoperative statin use on the probability of developing POAF,
while controlling for the baseline risk of POAF and the use of amiodarone
prophylaxis (AMP). A baseline risk index was calculated for each patient using a
previously validated model. Patients with chronic atrial fibrillation or missing
data were excluded. Results: Mean patient age was 63 (SD=13) years, 73% were
male, 68% underwent isolated coronary artery bypass grafting, 16% underwent
isolated valve surgery, with 13% underwent combined CABG and valve surgeries, and
3% underwent other forms of cardiac surgery. POAF occurred in 27% of patients
receiving statins and 24% of those not receiving statins (p=0.3792). After
controlling for baseline risk of POAF and the use of AMP, we found that
preoperative statins were not associated with reductions in POAF (OR=1.19,
95%CI=0.782-1.822, p=0.4118). Conclusions: Multiple factors impact the
development of POAF after cardiac surgery including patient demographics,
comorbidities, surgical type, and concomitant medications. In this study, after
adjustment for these factors the preoperative use of statins did not
significantly influence the development of POAF.
PMID- 28496691
TI - Comments on: Clinical Significance of Early Recurrences of Atrial Tachycardia
After Atrial Fibrillation Ablation by Choi JI et al.
PMID- 28496692
TI - Head Up Tilt Testing: An Appraisal of Its Current Role in the Management of
Patients with Syncope.
AB - Head up tilt testing (HTT) is now commonly used to investigate otherwise
unexplained syncope and presyncope. This test has been used for over 20 years
primarily to diagnose neurally mediated syncope, but HTT's exact role in the
diagnostic process remains uncertain. Recognized limitations include poor
reproducibility, lack of prognostic role, and insufficient randomized studies to
guide therapeutic choice. In this review, we describe the indications and methods
recommended by present guidelines on utilizing HTT. In addition, present
criticisms and limitations of this test, along with future perspectives, are
outlined.
PMID- 28496693
TI - Ablation of Atrial Fibrillation in the Elderly: Current Evidence and Evolving
Trends.
AB - Management of atrial fibrillation in the elderly presents unique challenges,
including deciding upon the best treatment strategy: rate control versus rhythm
control. The decision to pursue one treatment strategy over another is based on
understanding the underlying disorder: symptomatology from atrial fibrillation
itself versus symptoms due to a rapid ventricular response from atrial
fibrillation. The ablation strategies for the treatment of atrial fibrillation
include atrioventricular junction ablation and pulmonary vein isolation. This
review discusses the data on ablation of atrial fibrillation in the elderly, with
an emphasis on issues regarding safety and efficacy in this population.
PMID- 28496694
TI - Do Statins Reduce Atrial Fibrillation After Coronary Artery Bypass Grafting?
AB - Background: Atrial Fibrillation (AF) is a common postoperative complication after
coronary artery bypass grafting. There is contradictory evidence as to whether
pre-operative statin use lowers the incidence of postoperative AF. This study
aimed to assess whether pre operative statin therapy prevents the post-operative
AF. Methods: In this retrospective cohort study we used a propensity score
matching analysis to evaluate the effect of preoperative treatment with statins
on postoperative atrial fibrillation. There were 427 matched pairs of patients.
Primary outcome was the incidence of postoperative AF. Secondary outcomes were 30
day mortality, stroke, myocardial infarction and length of hospital stay.
Results: The incidence of postoperative AF was not different in the statin users
compared with the nonusers (123, 28.1%, versus 127, 29.7%, respectively; p =
0.764). The 30 day mortality (6, 1.4%, versus 8, 1.9%; p = 0.590), stroke (10,
2.3%, versus 8, 1.9%; p = 0.634), myocardial infarction (2, 0.5%, versus 0, 0.0%;
p = 0.499) and length of hospital stay in days (11.8 +/- 9.0, versus 11.9 +/-
9.3; p = 0.544) did not differ significantly between the two groups. Conclusions:
In a propensity-matched cohort of patients undergoing coronary bypass surgery, we
could not demonstrate that preoperative statins were protective for the
development of post operative atrial fibrillation.
PMID- 28496695
TI - Quinidine for Pharmacological Cardioversion of Long-lasting Atrial Fibrillation.
AB - Background: In the daily clinical practice, patients with atrial fibrillation
(AF) lasting more than 48h (or not datable at all) are not uncommon. In long
lasting AF changes in electrophysiological features (electrical remodeling) can
occur, resulting in a loss of sensibility to most antiarrhythmic drugs. There is
strong evidence that the main mechanism involved in electrical remodeling is a
global shortening in refractory period. To assess safety and efficacy of
quinidine in pharmacological cardioversion of long-lasting AF, compared with
propafenone and amiodarone. Methods and Results: Ninety consecutive patients with
AF lasting more than 6 weeks were randomized to amiodarone (5mg?kg bolus, then
15mg?kg in 24h) , propafenone (2 mg?kg bolus then 0.007mg?kg for 2h), and
quinidine (275mg of quinidine arabogalattan sulphate per os every 2h for 8h
maximum) for pharmacologic cardioversion. All patients had been previously
treated with adequate oral anticoagulation and had been submitted to
transthoracic echocardiogram. The 3 groups of patients did not differ for
baseline and echocardiographic characteristics. Sinus rhythm was restored in 16
patients treated with quinidine (53%), compared with 6 patients (20%) in the
amiodarone and propafenone groups (p<0.01). No major adverse effect was reported
during the treatment. Conclusions: Quinidine seems to be safe and effective in
pharmacological cardioversion of long-lasting AF.
PMID- 28496696
TI - Irrigated-Tip Magnetic Catheter Ablation Of AF: ALong-Term Prospective Study In
130 Patients.
PMID- 28496697
TI - Association of Left Atrial Fibrosis Detected by Delayed Enhancement Magnetic
Resonance Imaging and Risk of Stroke in Patients with Atrial Fibrillation.
PMID- 28496698
TI - Cardiac Resynchronization Therapy and Atrial Fibrillation.
AB - Cardiac resynchronization therapy (CRT) is an important advance for the treatment
of end--stage heart failure (HF). About 15-50% of HF is complicated by atrial
fibrillation (AF) and associated with worsened outcomes. Meta-analyses from
observational studies suggest that patients with AF derive similar benefits to
CRT as patients in sinus rhythm (SR). The presence of AF, however, may interfere
with optimal delivery of CRT due to competition with biventricular (BiV) capture
by conducted beats. Atrioventricular junction (AVJ) ablation with permanent
pacing eliminates interference by conducted beats and provides complete BiV
capture. Catheter ablation of AF is an alternative to antiarrhythmic drugs to
maintain sinus rhythm in patients with AF and HF. Randomized trial comparing
catheter ablation, AVJ ablation and pharmacologic therapy are needed.
PMID- 28496699
TI - Complications of Radiofrequency Catheter Ablation for Atrial Fibrillation.
AB - Radiofrequency catheter ablation (RFA) has evolved as an effective treatment
modality in patients with atrial fibrillation (AF). However, complication rates
associated with RFA of AF have been cited in the range of 3.5 - 5% with the
majority consisting of cardiac tamponade, vascular complications, and
thromboembolic phenomena. In this review, the complications of AF ablation will
be discussed along with associated clinical management strategies.
PMID- 28496700
TI - IntravenousCorticosteroid Use Is Associated With Reduced Early Recurrence of
Atrial Fibrillation Immediately Following Radiofrequency Catheter Ablation.
AB - Background: Early recurrence of atrial fibrillation (ERAF) occurs in up to 40% of
patients after radiofrequency catheter ablation for atrial fibrillation (RFCA),
increasing hospital stay, need for anti-arrhythmic medications (AADs) and
cardioversion, and, possibly, the risk of future AF. It has been postulated that
inflammation plays a key role in developing ERAF. Short term postoperative use of
corticosteroids to reduce ERAF post-RFCA has not been vigorously studied.
Methods: This was a case-control study of consecutive patients undergoing RFCA
for the management of AF at a single-institution. RFCA was performed by a single
operator from October 2005 through July 2009. Patients receiving intravenous
corticosteroids immediately following the ablation and for 48 hours (6 doses)
constituted the treatment group. Controls received no intravenous corticosteroids
during their hospitalization. All other management strategies were similar
between the 2 groups, including the administration of AADs post- operatively. All
patients had continuous electrocardiographic monitoring throughout their
hospitalization. Multivariable logistic regression analysis was used to determine
the impact of intravenous corticosteroids on ERAF defined as any AF>10 minutes
during hospitalization. Results: A total of 68 patients undergoing RFCA for the
management of AF were included in this analysis. The overall ERAF rate,
irrespective of intravenous corticosteroid use, was 23.5%. The administration of
intravenous corticosteroids (n=37; mean+/-SD dexamethasone mean dose 11.9+/-4.6
mg/day; range 4-16 mg/day) was associated with an 82% reduction in patients' odds
of ERAF (adjusted odds ratio; 0.18, 95% confidence interval [CI] 0.04 to 0.78)
compared with those who did not receive corticosteroids (n=31). A dose-response
effect was also observed, with a 17% reduction in ERAF odds for each
dexamethasone mg-equivalent administered (adjusted odds ratio; 0.83, 95%CI 0.73
to 0.96). Conclusions: The use of intravenous corticosteroids was associated with
a dose-dependent reduction in the odds of developing ERAF after RFCA for the
management of AF.
PMID- 28496701
TI - Atrial Fibrillation After Lung Transplantation: Incidence, Predictors and Long
Term Implications.
AB - Background: Little is known about the frequency of, risk factors predisposing to,
and long-term impact of post-operative atrial fibrillation (AF) after lung
transplantation. Methods: A prospectively collected registry of 167 consecutive
patients who underwent single or bilateral lung transplantation at the University
of Minnesota Medical Center from January 1st, 2004 to December 30th, 2008 was
reviewed. Post-operative AF was confirmed by review of electrocardiograms by two
cardiologists. Kaplan-Meier survival curves were constructed to determine the
impact of new onset AF on long-term survival. Results: The mean age (+/-SD) of
the population was 55 +/- 11 years and 52% were male. A total of 48 patients
(28%) developed AF in the postoperative period. Predictors of postoperative AF in
multivariate analysis included: age (per decade) Odds Ratio (OR): 1.61, 95%
confidence interval (CI) 1.10-2.34, p=0.01, postoperative thromboembolic disease
OR: 9.73 (95% CI: 2.16-43.81, p<0.01, and postoperative pericarditis OR: 3.57,
(95% CI: 1.38-9.22, p < 0.01). Of the 48 patients who developed post-operative
AF, 41 were discharged in sinus rhythm (SR). Survival among patients who were
discharged in AF was significantly lower when compared to patients discharged in
SR (HR: 0.08; 0.01-0.43, p<0.05). Conclusions: Postoperative AF is common after
lung transplant. Increased age, postoperative thromboembolic disease, and
pericarditis are independent predictors of postoperative AF. Persistence of AF at
the time of discharge is an identifier of decreased survival.
PMID- 28496702
TI - Neuropsychological Decline After Catheter Ablation of Atrial Fibrillation.
PMID- 28496703
TI - Atrial Coronary Arteries: Anatomy And Atrial Perfusion Territories.
AB - Coronary anatomy has traditionally focused on ventricular circulation. This is
largely due to the extent to which coronary artery disease contributes to
ischemic heart disease through ventricular myocardial damage. Atrial fibrillation
and other tachyarrhythmias that involve the atria, however, remain a major cause
of morbidity and mortality. In order to increase mechanistic research and
therapeutic interventional procedures for diseases of the atria, an optimal
knowledge of atrial anatomy is necessary. While substantial clarity exists
regarding the distribution of nerve terminals and the organization of muscle
bundles, the anatomy of coronary atrial circulation remains understudied.
Historically, the high anatomical variability of atrial coronary branches led to
unstandardized nomenclature in the literature. In this review, we delineate the
anatomic courses of key atrial coronary branches and their perfusion territories,
clarify their nomenclature, and propose unifying anatomical concepts of atrial
circulation that we believe to be critical to the success of modern
electrophysiologic and surgical procedures.
PMID- 28496704
TI - Metformin associated Atrial Fibrillation - A Case Report.
PMID- 28496705
TI - Role of Echocardiography in Atrial Fibrillation Ablation.
AB - Radiofrequency catheter ablation is an increasingly adopted strategy for
difficult-to-manage patients with atrial fibrillation. Echocardiography is the
key imaging modality to assess left atrialstructure and function. In this review,
the role of echocardiography in atrial fibrillation ablationbefore, during and
after ablation is discussed. Currently established roles of echocardiography
inpatient selection pre-ablation and peri-procedural guidance, as well as newer
echocardiographic techniques including the assessment of atrial mechanics are
reviewed in the context of atrial fibrillation ablation.
PMID- 28496706
TI - Renin-Angiotensin System and AtrialFibrillation:Understanding the Connection.
AB - Atrial fibrillation (AF) arises as a result of a complex interaction of triggers,
perpetuators and the substrate. The recurrence of AF may be partially related to
a biologic phenomenon known as remodeling, in which the electrical, mechanical,
and structural properties of the atrial tissue and cardiac cells are
progressively altered,creating a more favorable substrate. Atrial remodeling is
in part a consequence of arrhythmia itself. Therefore,to prevent and to treat AF,
much attention has been directed to upstream therapies to alter the arrhythmia
substrate and to reduce atrial remodeling. The renin-angiotensin-aldosterone
system (RAAS) plays a keyrole in these strategies. In this review we analyze the
experimental and clinical evidence regarding the efficacy of RAAS inhibitors in
AF treatment. In the primary prevention of AF, meta-analyses have shown that risk
of new-onset AF in patients with congestive heart failure and left ventricular
dysfunction is reduced by RAAS inhibitors, whereas in hypertensive and post
myocardial infarction patients, the results are less evident. In the secondary
prevention of AF, some large, prospective, randomized, placebo-controlled
studieswith angiotensin II-receptor blockers returned negative results.
Unfortunately, the approach of using RAASinhibitors as antiarrhythmic drugs to
prevent both new-onset and recurrent AF is in decline because negativetrial
results are accumulating, with the exception of the results in patients with
congestive heart failure.
PMID- 28496707
TI - Stretch and Inflammation- Their Relation to Fractionation of Electrograms in
Atrial Fibrillation.
AB - BACKGROUND: Inflammatory markers (IM) are elevated in atrial fibrillation (AF).
However the relation of IM to substrate modificationinAF remains unclear.We
sought to assess the relationship of IM to fractio ated atrial electrogram (FAE)
in patients undergoing AF ablation. METHODS: At baseline, left atrial (LA)
pressure was recorded and peripheral blood was tested for IM. FAE mapping
wasperformed before and after circumferential pulmonary vein and linear ablation
(CPVA-L) and followed by FAEablation. Image processing was used to define the FAE
areas. AF cycle-length (AFCL) was compared between baseline and after ablations
from left atrial electrode. RESULTS: Older patients had higher cytokine levels.
FAE area at baseline (secondary FAE) negatively correlated with the levels of
interleukin-6 (IL-6, R2= -0.97 and p=0.03) and interleukin-12p70 (IL-12p70, R2=
0.97 and p=0.03). In addition, a significant reduction in FAE area and index
occurred after CPVA-L (p=0.0001). FAE after CPVA-L (primary FAE) correlated with
left atrial pressure (LAP), [R2 0.5, (p=0.02)]. The AFCL (in msec) increased from
135 +/- 41 to 149.5+30 (p=ns) after CPVA-L and further increased to 191.5 +/- 60
(p=0.007) after FAE ablation. CONCLUSIONS: There is a negative correlation of IL
6 and IL-12p70 to baseline FAE, suggesting a possibility of sequestration of
these cytokines in left atrium. CPVA-L ablation reduces FAE area which when
ablated increases AFCL, suggesting that these areas likely represent primary
fragmentation due to rotors, triggered by atrial stretch as seen by the relation
of left atrial pressure and post CPVA-L FAE.
PMID- 28496708
TI - Risk Alteration for Atrial Fibrillation with DifferentAntihypertensive Drugs.
AB - A large percentage of patients with hypertension suffer from atrial fibrillation
(AF). The concomitance of both conditions in the same patient markedly increases
cardiovascular risk. Therefore, prevention of new-onset AF in hypertensive
population should be a relevant target. High blood pressure promotes structural
and electrophysiological changes in the heart that promote the develop- ment of
AF. Thus, the most important therapeutic approach to prevent incident AF in
hypertensive population is to reduce blood pressure values to recommended goals.
However, in specific conditions, some antihypertensive agents may provide
additional benefits beyond blood pressure reduction, such as in hypertension with
left ven- tricular hypertrophy with renin angiotensin system blockade. On the
other hand, in patients with hypertension and permanent AF, beta blockers and
nondihydropiridine calcium antagonists (verapamil and diltiazem) play an
important role. Antihypertensive agents may provide beneficial effects on
incident AF, regardless of the presence of hyperten- sion. Thus, renin
angiotensin system inhibitors may reduce new-onset AF in patients with heart
failure or after the cardioversion of persistent AF. On the other hand, the
preoperative administration of beta blockers may re- duce the incidence of
postoperative AF in some patients. In this manuscript, the available evidence
about the effects of different antihypertensive agents on new-onset AF in
different populations is reviewed.
PMID- 28496709
TI - Atrium-Atrioventricular Node Conduction Block during Catheter Ablation of
Persistent Atrial Fibrillation.
AB - Previous studies have suggested that fibrillatory substrates are widely
distributed in both atria in patients with persistent atrial fibrillation.
Extensive bi-atrial ablation has been increasingly performed to improve the
clinical outcomes; however, this may adversely affect the intra-atrial conduction
during sinus rhythm. The worst con- sequence of an intra-atrial conduction
disturbance is conduction block between the atrium and atrioventricular node.
There have been a few case reports on this complication, which suggest that the
conduction block may occur more. This review aimed to describe the risk factors
and method of prevention of atrium-atrioventric-ular node conduction block.
PMID- 28496710
TI - Prevention of Stroke in Patients With Atrial Fibrillation.
AB - The presence of atrial fibrillation (AF) increases the risk of stroke, especially
in patients with risk factors as outlined by the CHADS2 and CHA2DS2-VASc scoring
systems. Although warfarin can reduce stroke rates by over 65%, only 55% of
patients, in the USA, who should be on warfarin for AF and stroke prevention are
taking the drug due to the need of INR monitoring, difficulties in maintaining a
therapeutic INR in the therapeutic range and dietary and drug interactions.
Dabigatran, an oral direct thrombin inhibitor and rivaroxaban and apixaban,
factor Xa inhibitors, have demonstrated efficacy in reducing stroke in large
clinical trials. These novel anticoagulants will change the therapeutic landscape
since patients will be able to prevent stroke with a lower risk of intracranial
hemorrhage and without the need for INR monitoring and less drug-dietary
interactions.
PMID- 28496712
TI - The Concept of "Burden" in Atrial Fibrillation.
AB - Over the last decade or so the term "burden" has become frequently encountered in
manuscripts discussing atrial fibrillation (AF). AF "burden" is perhaps most
commonly encountered in the electrophysiological context - the amount of time the
patient is in AF out of the total monitored time (i.e., the percent of time one
is in AF). However, "burden" in AF may also be used in other contexts, which we
characterize below as "disease burden", "clinical burden," "economic burden."
Over the course of the disease progression and its therapy, such "burdens" may
change, and may do so in parallel with each other or in opposite directions. This
manuscript explores these various concepts of AF "burden" so as to emphasize to
authors and readers that when using the term, its meaning must be made clear.
PMID- 28496711
TI - Catheter Ablation of Atrial Fibrillation in Overweight and Obese Patients.
AB - Obesity has reached epidemic proportions, and is associated with increased all
cause mortality. Atrial fibrillation(AF), the most common sustained arrhythmia in
the clinical practice, is associated with an increased longterm risk of stroke,
heart failure, and all-cause mortality. Accumulating data points out to an
indispensable role of inflammation in both obesity and AF. Recent studies have
documented an increasing risk of AF with increasing body mass index (BMI). The
pathophysiological alterations associated with overweight and obesity lead to
atrial stretch and atrial enlargement creating the substrate for AF development.
Catheter ablation of AF has been widely accepted as an important therapeutic
modality for the treatment of patients with symptomatic,drug-refractory AF.
Previous studies assessing the impact of BMI on AF catheter ablation outcomes
have given conflicting data. Given that overweight and obesity, as defined by
BMI, and AF are closely linked,the present review sought to investigate the
impact of BMI on the efficacy and safety of AF catheter ablation.
PMID- 28496713
TI - A Novel Transgenic Mouse Model of Cardiac Hypertrophy and Atrial Fibrillation.
AB - Cardiac hypertrophy is a major risk factor for the development of atrial
fibrillation (AF). However, there are few animal models of AF associated with
cardiac hypertrophy. In this study, we describe the in vivo electrophysiological
characteristics and histopathology of a mouse model of cardiac hypertrophy that
develops AF. Myostatin is a well-known negative regulator of skeletal muscle
growth that was recently found to additionally regulate cardiac muscle growth.
Using cardiac-specific expression of the inhibitory myostatin pro-peptide, we
generated transgenic (TG) mice with dominant-negative regulation of MSTN (DN
MSTN). One line (DN-MSTN TG13) displayed ventricular hypertrophy, as well as
spontaneous AF on the surface electrocardiogram (ECG), and was further evaluated.
DN-MSTN TG13 had normal systolic function, but displayed atrial enlargement on
cardiac MRI, as well as atrial fibrosis histologically. Baseline ECG revealed an
increased P wave duration and QRS interval compared with wild-type littermate
(WT) mice. Seven of 19 DN-MSTN TG13 mice had spontaneous or inducible AF, while
none of the WT mice had atrial arrhythmias (p<0.05). Connexin40 (Cx40) was
decreased in DN-MSTN TG13 mice, even in the absence of AF or significant atrial
fibrosis, raising the possibility that MSTN signaling may play a role in Cx40
down-regulation and the development of AF in this mouse model. In conclusion, DN
MSTN TG13 mice represent a novel model of AF, in which molecular changes
including an initial loss of Cx40 are noted prior to fibrosis and the development
of atrial arrhythmias.
PMID- 28496714
TI - South Asians are Under-Represented in a Clinic Treating Atrial Fibrillation in a
Multicultural City in the UK.
AB - The Leeds rapid access atrial fibrillation (AF) clinic was set up to streamline
and standardise management of patients with newly diagnosed AF. Anecdotal
evidence suggests that there is under-representation of south Asians in these
clinics.All patient attendances between June 2007 and June 2011 were documented
and combined with ethnicity data from patient administration records. Local
population demographics for 2009 were obtained from the office of national
statistics. This was used to estimate the expected prevalence of AF across the
different ethnic groups in Leeds taking age into account. One thousand two
hundred and ten patients were referred. The study sample included 992 patients,
and the number of south Asians attending was 88% less than expected (Chi squared
analysis; p<0.0001). These results suggest that there is an under-representation
of south Asians in a large centre that serves a cosmopolitan population.
Potential reasons for this discrepancy including barriers to accessing treatment
for this population or a lower prevalence of AF in south Asians due to an as yet
unidentified genetic factor.
PMID- 28496715
TI - Role of Echocardiography in the Management and Prognosis of Atrial Fibrillation.
AB - Echocardiography plays a longstanding and vital role in the management of atrial
fibrillation (AF). Advances in 2D imaging, Doppler echocardiography and strain
imaging have all contributed to major progress in AF treatment.
Echocardiographically measured left atrial (LA) volume is a powerful predictor of
maintenance of sinus rhythm following cardioversion as well as risk of thrombus
formation and thromboembolism. Doppler derived parameters of atrial mechanical
function including atrial ejection force provide related prognostic information.
Transesophageal echocardiocardiograpy (TEE) guided cardioversion of AF allows for
rapid conversion to sinus rhythm without prolonged oral anticoagulation, and TEE
serves as a useful tool during catheter ablation of AF and atrial flutter. Newer
measures derived from speckle tracking offer great promise in further improving
the care of patients with AF.
PMID- 28496716
TI - Left Atrial Diastolic Dysfunction following Catheter Ablation of Atrial
Fibrillation.
AB - Radiofrequency catheter ablation (RFCA)-induced thermal injury may cause and/or
worsen left atrial (LA) diastolic dysfunction leading to pulmonary hypertension
and heart failure in patients with atrial fibrillation (AF), the incidence of
which is probably more common than is generally realized. Biplane 2-dimensional
echocardiography coupled with tissue Doppler (velocity) imaging and Doppler
derived strain (rate) imaging can be applied to provide quantitative assessment
of the LA function (both systolic and diastolic) relative to pulmonary venous
circulation and left ventricular function. Information so obtained is useful for
guiding follow-up management of patients undergoing RFCA of AF.
PMID- 28496717
TI - Necessity of Repeat Ablations to Eliminate Atrial Fibrillation.
AB - Atrial fibrillation (AF) is the most common human arrhythmia and leads to
increased morbidity and mortality. Because of demographic changes, the prevalence
of AF will increase in the next decades, requiring better primary prevention
strategies and better treatment options. In 1998, Haissaguerre et al. described
triggering foci in the pulmonary veins (PV) as the prevailing pathophysiological
initiator of paroxysmal AF. Since then, multiple studies have been conducted
using the technique of pulmonary vein isolation (PVI) to eliminate AF. In short
term follow-up, success rates of 60-75% in patients with paroxysmal AF are
reached, with significantly worse results in persistent AF of approximately 50%.
Due to arrhythmia recurrence, multiple procedures are often necessary, especially
in patients with persistent AF, to achieve these results. It is supposed that the
cause of arrhythmia recurrence is pulmonary vein reconnection in patients with
paroxysmal AF, and insufficient substrate modification or new substrate
development in patients with persistent AF. Future techniques like contact force
control might improve lesion formation leading to improved PVI and substrate
modification.
PMID- 28496718
TI - Adverse Outcomes from Atrial Fibrillation;Mechanisms, Risks, and Insights Learned
from Therapeutic Options.
AB - Atrial Fibrillation (AF) continues to increase in prevalence and its'
consequences and disease associations have a great impact on multiple aspects of
medical practice. As such, making preventive strategies to minimize risk of the
arrhythmia and its' complications are paramount to improve quality of life,
mortality, and limit medical resource utilization. To the extent that AF
independently impacts adverse cardiovascular outcomes, this review article will
focus on these outcomes, in particular heart failure (HF), stroke, and mortality,
and discuss contemporary strategies for treatment. Conclusions: AF has a marked
deleterious impact on the lives of patients. This impact can be accelerated when
other cardiac diseases coexist. Although rhythm control strategies have been an
intriguing tool to reverse or minimize the adverse outcomes associate with AF,
they have largely been unsuccessful. In general, failures of currently available
AADs to improve survival are due to failure of the drug to maintain sinus rhythm
and presence of drug toxicities. Early data with ablation approaches are
favorable and support rhythm control strategies to minimize long-term risks
associated with AF. However, most of the data stem from observational analysis or
small randomized trials. Large randomized prospective trials will ultimately
define the role of catheter ablation in the management of AF patients.
PMID- 28496719
TI - Collateral Damage During Ablation of Atrial Fibrillation - Lessons Learnt in the
Past Decade.
PMID- 28496720
TI - Age as a Risk factor for Atrial Fibrillation and Flutter after Coronary Artery
Bypass Grafting.
PMID- 28496721
TI - Phrenic Nerve and Esophageal Injury During Catheter Ablation of Atrial
Fibrillation.
AB - Atrial fibrillation is a common cardiac arrhythmia with rapid and irregular
atrial activity. Although radiofrequency catheter ablation of atrial fibrillation
has became an established treatment for the management of symptomatic drug
refractory patients in the past decade, several complications due to the
procedure have been reported. The purpose of this review article is to describe
the collateral damage from catheter ablation of atrial fibrillation.
PMID- 28496722
TI - Predictors of Recurrence After Catheter Ablation of Persistent Atrial
Fibrillation.
AB - Catheter ablation of atrial fibrillation (AF) has been increasingly used to treat
symptomatic patients.Within the last years a growing interest in ablation of
persistent AF forms has evolved.Factors that may influence outcome of these
procedures to treat persistent AF may be patient-specific (pre
procedural),procedure-related or may involve different post-ablation followup
strategies. In this review potential factors predicting recurrence of AF after
ablation of persistent AF have been evaluated.In essence, data is limited mostly
due to incongruent definitions of persistent AF.Left atrial dimensions, duration
of continuous AF and AF cycle length may be patient-specific predictors of
outcome. Intra-procedural parameters involved in recurrence prediction may be
extent of ablation (effective pulmonary vein isolation appears mandatory) and
termination of AF during ablation. Timing and number of cardioversion if
persistent AF recurs may predict outcome, as well. Many studies have identified
strators for higher recurrence rates in rather small patient groups and need to
be further evaluated in larger patient collectives.
PMID- 28496723
TI - Conversion of Persistent Atrial Fibrillation After Radiofrequency Ablation by
Ibutilide.
AB - Ablation of peristent AF remains challenging with questions unanswered about what
the ideal next step after pulmonary venous isolation should be. Ibutilide is a
highly effective class III agent for cardioversion of acute-onset atrial flutter
and fibrillation, with limited clinical use due to risks of ventricular pro
arrhythmias. However, results from the on-going MAGIC-AF trial may re-invigorate
its role in clinical electrophysiology as an invaluable adjunct to facilitate
controlled substrate modification during ablation of persistent AF.
PMID- 28496724
TI - Non-interventional Management of Symptomatic Pulmonary Vein Occlusion after
Radiofrequency Ablation for Atrial Fibrillation.
AB - Pulmonary vein occlusion (PVO) after atrial fibrillation ablation is often highly
symptomatic. In cases with a clear target, balloon angioplasty and stenting can
be successful. In the absence of such a target, surgical lobectomy has been
reported as a treatment option, but the natural history of physiological
adaptation may outweigh the risks of invasive therapies and a non-invasive
strategy is valid in these situations. We present a case of highly symptomatic
PVO managed non-invasively, with complete symptom resolution and return to high
intensity exercise. Catheter intervention may not always be possible in the
absence of a target vessel, and lobectomy may not be necessary to manage PVO.
PMID- 28496725
TI - Preventative Measures of Stroke in Patients With Atrial Fibrillation.
AB - Atrial fibrillation (AF) is the commonest sustained cardiac arrhythmia and is
associated with increased morbidity and mortality due to stroke and thrombo
embolism. In patients with AF, strokes are usually more severe, resulting in
longer hospital stays, worse disability and considerable healthcare costs. The
prevention of stroke therefore is crucial in the management of AF. Stroke risk
stratification tools can be used to determine patients at higher risk of stroke,
and if no contraindications are present oral anticoagulation (OAC) therapy can be
initiated. Despite the strong evidence for the benefit of OAC in stroke
prevention in patients with AF, the use of thromboprophylaxis remains inadequate.
The key measures to prevent stroke in patients with AF include: adequate stroke
risk assessment and thrombo-prophylaxis; prompt initiation of OAC and avoidance
of interruptions; earlier detection of AF; and education to overcome the under
usage of OAC in elderly patients.
PMID- 28496726
TI - Outcome of Patients Discharged after their First Detected Episode of Atrial
Fibrillation.
AB - Atrial fibrillation (AF) is the most frequent supraventricular arrhythmia with an
approximative prevalence of 1 % in the general population and above 6 % in the
elderly. After a first AF diagnosis, the hospitalization rate is markedly
increased. Management of a first AF episode is different depending on the
clinical status of patients. Practical guidelines developed in collaboration with
the European Heart Rhythm Association and the Heart Rhythm Society are available
for the management of these patients. A four-step decisional scheme must be
followed in the management of a first recent AF episode: need for a short- and
long-term anticoagulation, define a rythmologic strategy (rhythm or rate
control), select the weapon (drug, device or ablation) and reconsider the
strategy if needed. After a first uncomplicated paroxysmal AF episode, guidelines
recommend that prescription of antiarrhythmics must be avoided and
anticoagulation is optional. After a first persistent AF episode, guidelines
recommend to either respect or reduce the arrhythmia. Prescription of
antiarrhythmics and anticoagulation is also optional depending on the patient?s
condition. In case of the AF reduction decision, anticoagulation must be tailored
preliminary to this reduction. AF recurrence rate varies depending on the
patient?s condition, and the risk of stroke assessed by the CHA2DS2-VASc score
might be similarly considered for both paroxysmal and persistent AF.
PMID- 28496727
TI - Risk Factors for the Development of Atrial Fibrillation in HIV Infected Patients.
AB - Background: Patients with Human Immunodeficiency Virus (HIV) have an array of
multi-organ involvement, including cardiovascular disease. CD4 count is one of
the best parameters to monitor the severity of HIV disease. The arrythmogenic
potential of HIV disease has not been well defined. The aim of the study is to
establish whether an association between the severity of HIV and atrial
fibrillation (AF) exists. Methods: Out of a retrospective cohort of 780 HIV
patients from January 2006 to December 2008, 40 patients were selected that
developed AF during this period .The age and sex matched controls (n=40) were
selected for comparison. The comparison between both groups was done using
Fischer Exact Test. Bivariate and multivariate analysis was also performed to
analyze the results. Results: The data shows that 47%(19/40) of the patients with
HIV who developed AF had CD4 count lower than 250 as compared to 20%(8/40) in the
control group (P value = 0.017) Conclusion: The data supports the presence of a
relationship between HIV and AF. Patients with lower CD4 counts are more
susceptible to develop AF.
PMID- 28496728
TI - Risk of Arrhythmia Recurrence After Successful Ablation of Lone Atrial
Fibrillation.
PMID- 28496729
TI - Cardiac Resynchronization Therapy in Patients with Atrial Fibrillation - Worth
the Effort?
AB - Congestive heart failure (CHF) and atrial fibrillation (AF) are two increasingly
common conditions that predispose to each other and frequently coexist. Cardiac
resynchronization therapy(CRT) has emerged as an important therapeutic modality
for selected patients with end-stage CHF. However, despite the high prevalence of
AF in patients eligible for CRT, almost all the randomized clinical trials that
validated the benefit of resynchronization therapy excluded patients with
preexisting AF. In this review, we examine the available evidence on the benefits
and limitations of CRT in patients with AF and discuss recent data that narrowed
the knowledge gap on this topic.
PMID- 28496730
TI - Demographic Characteristics and Patterns of Medication in Atrial Fibrillation
Patients in South West Ontario: Insights from a Large Primary Care Database.
AB - Background: Information about current practice in primary care-based management
of atrial fibrillation (AF) can help to improve care quality. Purpose: To assess
the epidemiology of AF and current patterns of treatment in order to identify
therapeutic trends and aspects of current practice that may allow for care-gap
identification. Methods: We scrutinized the anonymized records of the South
Western Ontario database (SWO) collected between July 2002 and October 2008 for
information about the characteristics and management of AF patients. Results:
From a population of ~168,000 patients we identified 4922 patients with a
diagnosis of AF (2.9%). The recorded prevalence of AF increased with age, from
<2% at age <60 years to 6% in the age range 71-75 years and 10% at age >=81
years. AF patients were characterized by an unfavourable cardiovascular risk
profile including widespread hypertension (54% of all cases), coronary artery
disease (37%) and heart failure (21%), many cases of which were advanced (New
York Heart Association class III or IV). Diabetes (22%) and dyslipidaemia (31%)
were also widely prevalent. The most frequently prescribed anti-arrhythmic drugs
(AADs) were sotolol (n=798), amiodarone (n=712) and propafenone (n=451). Recorded
use of flecainide was relatively low (n=175). Rate control-agents were being
prescribed for 1838 patients, beta-blockers for 1311 patients and calcium channel
blockers (CCBs) for 784 patients. Use of anticoagulants was higher among patients
assigned to AADs than among those assigned to rate-control drugs (>25% vs. ~10%).
Overall prescription rates for other concomitant medications were >50% for ACE
inhibitors/ARBs, 30-35% for statins and beta-blockers, and 27-29% for diuretics,
digoxin and CCBs. Conclusions: These Canadian patients with AF were relatively
elderly and had multiple concomitant cardiovascular conditions and medications.
PMID- 28496731
TI - Enhancing Cardiac Resynchronization Therapy for Patients with Atrial
Fibrillation: The Role of AV Node Ablation.
AB - Cardiac resynchronization therapy (CRT) has evolved as an effective therapy for
patients with congestive heart failure (CHF) and ventricular dyssynchrony,
currently defined as a wide QRS on the electrocardiogram. While multiple
randomized controlled trials have confirmed the favorable effects of CRT on
mortality and heart failure symptoms for patients in sinus rhythm, only recently
observational studies have begun to suggest a similar benefit for patients with
atrial fibrillation (AF) and dyssynchrony. Yet, implementing effective
biventricular pacing in patients with AF can be problematic due to competing
intrinsic AV conduction. For patients with depressed ejection fractions needing
AV node (AVN) ablation to control fast ventricular rates, biventricular pacing
has been shown to be superior to right ventricular pacing alone. When consistent
pacing (over 90% of the time) cannot be achieved in AF patients due to a rapid
ventricular response despite pharmacological therapy, AVN ablation should be
considered. The additional benefit of performing AVN ablation to promote
biventricular pacing in patients without rapid ventricular rates remains
uncertain. A randomized controlled trial is needed to test the incremental
benefit of AVN ablation to promote biventricular pacing in heart failure patients
with AF and wide QRS.
PMID- 28496732
TI - Atrial Fibrillation and Oral Anticoagulation in Chronic Kidney Disease.
AB - Due to several unfavorable epidemiological changes, chronic kidney disease (CKD)
and treatment of its associated cardiovascular morbidity have become a worldwide
problem. Thus, atrial fibrillation (AF) is the most common arrhythmia and
frequently associated with renal impairment: prevalence for AF is up to 27% in
long-term hemodialysis patients and in general more than 25% in all CKD patients
70 years and older. Thromboembolism and stroke are the major complications of AF.
Two-year death rates for CKD patients after stroke range between 55% and 74%.
Although treatment of AF in the general population is well defined, patients with
CKD and AF are often undertreated due to lack of studies and guidelines. In this
review recent data concerning incidence and prevalence of AF, stroke, and major
bleedings in CKD patients are presented. Particular attention is paid to the
available data about the different types of oral anticoagulation therapy with
regard to CKD stage, including the new oral anticoagulant drugs dabigatran,
rivaroxaban, and apixaban. Stratification algorithms for stroke risk in general,
and individualized risk stratification for oral anticoagulation in CKD patients
are discussed in detail.
PMID- 28496734
TI - Epicardial Fat and Atrial Fibrillation: A Review.
AB - Atrial fibrillation (AF) is a progressive disorder that increases with age.
Obesity is an important risk factor for AF. Pericardial fat is an active adipose
tissue in close proximity to the heart and has been shown to be a risk factor for
structural as well as coronary artery disease independent of body mass index.
Recent studies suggest a role of epicardial fat in atrial remodeling as well as
AF burden. This review will summarize the recent evidence linking epicardial fat
and AF.
PMID- 28496733
TI - Risks from Catheter Ablation of Atrial Fibrillation: A Review of Methods,
Efficacy, and Safety.
AB - Atrial fibrillation (AF) is the most common arrhythmia and is a significant
burden to healthcare cost. AF causes congestive heart failure, thromboembolic
events such as stroke and intolerable symptoms in some patients. With the
advances and increasing experience in catheter ablation, there is now an
established role for catheter ablation in patients with atrial fibrillation. The
risks, complications and patient features associated with it are increasingly
recognized. A recent worldwide survey has shown an increasing number of medical
centers that are practicing catheter ablation of atrial fibrillation,
predominantly with pulmonary vein isolation techniques. However, catheter
ablation is an invasive therapy in AF and is associated with a few major
complications. Patient selection, ablation technique, and catheter energy source
all influence the efficacy and safety of the procedure. Finally, while several
randomized control trials have compared the efficacy of catheter ablation versus
antiarrhythmic drug therapy, a number of trials are on the horizon to explore its
role as a first line therapy for atrial fibrillation. New energy catheter energy
sources are also being explored.
PMID- 28496735
TI - Treating Atrial Fibrillation With Cryoballoon Technology.
AB - Cryoballoon ablation has emerged as a novel tool to perform pulmonary vein
isolation. The aim of this paper is to review the advantages, drawbacks as well
as possible complications and clinical outcomes of this technology and to discuss
some important technical issues.
PMID- 28496737
TI - Temporal and Spatial Indices of AF Regularization Predict Intraprocedural AF
Termination and Outcome.
PMID- 28496739
TI - Anemia and Atrial Fibrillation.
PMID- 28496738
TI - Impact of Chronic Anemia on the New-Onset Atrial Fibrillation in the Elderly: It
May Not Be What We Have Thought.
AB - Objective: To determine if a clinically significant relation exists between
chronic anemia and the new-onset atrial fibrillation (AF) in the elderly
population from a community setting. Patients and Methods: This is a single
center community-based retrospective cohort study. Data were collected on 3867
patients over the age of 65 years presenting to the Mercy Medical Center in the
year 2006. Patients without AF were divided into anemic and non-anemic groups and
were followed over the next two years for the new-onset AF. Chronic anemia was
defined as hemoglobin level less than 13g/dl in males and less than 12g/dl in
females from two laboratory values checked at least 4 months apart. Results: Of
the 2873 patients without AF, 2382 (83%) patients were non-anemic. 491 patients
were anemic. New-onset AF was found in 7.5 % of the anemic patients and 5.5% of
the non-anemic patients. After the adjustment for comorbid conditions, chronic
anemia is not associated with new-onset AF (p=0.922). Conclusion: In this study
cohort of elderly community-based patients, chronic anemia is not associated with
the new-onset AF.
PMID- 28496736
TI - Altered Excitation-Contraction Coupling in Human Chronic Atrial Fibrillation.
AB - This review focuses on the (mal)adaptive processes in atrial excitation
contraction coupling occurring in patients with chronic atrial fibrillation.
Cellular remodeling includes shortening of the atrial action potential duration
and effective refractory period, depressed intracellular Ca2+ transient, and
reduced myocyte contractility. Here we summarize the current knowledge of the
ionic bases underlying these changes. Understanding the molecular mechanisms of
excitation-contraction-coupling remodeling in the fibrillating human atria is
important to identify new potential targets for AF therapy.
PMID- 28496740
TI - Atrial Fibrillation at an Internal Medicine Ward: Clinical and Prognostic
Implications.
AB - Background: Little is known about atrial fibrillation (AF) appearing during
hospitalization in an Internal Medicine ward. Purpose: We aimed to investigate
characteristics and prognostic significance of in-hospital onset AF. Methods: We
studied 249 consecutive unselected patients admitted to this medical department
with paroxysmal or persistent AF (out-of-hospital group) or AF developed during
hospitalization (in-hospital group). Demographic, clinical, laboratory,
electrocardiographic and echocardiographic data and all-cause mortality following
discharge were recorded and compared between the groups Results: Diabetes
mellitus (p=0.05), renal dysfunction (p<0.001), chronic lung disease (p=0.03) and
history of stroke (p=0.01) were found more common in the in-hospital group (56
patients), compared to the out-of-hospital group (193 patients). Patients from
the in-hospital group were more likely to have recurrent episodes of AF during
hospitalization (p=0.002), were more frequently treated with amiodarone
(p<0.001), discharged in sinus rhythm (p=0.04) and with medications for rhythm
control (p=0.04). Time from onset to termination of AF (p<0.001) and hospital
stay (p<0.001) were longer in the in-hospital group. On a median of 39-months
follow-up, survival rate was lower in the in-hospital vs. out-of-hospital group
(69.6% vs. 81.3%, p=0.025). Older age was significantly associated with shorter
survival in the in-hospital group [odds ratio (OR)=1.87, 95% confidence interval
(CI) 1.15-3.03, p=0.009]. In the out-of-hospital group, advanced age (OR=2.17,
95%CI 1.51-3.10, p<0.001), no prior AF episode (OR=3.41, 95%CI 1.56-7.46,
p=0.002), diabetes mellitus (OR=2.22, 95%CI 1.12-4.39, p=0.006) and renal
dysfunction (OR=2.44, 95%CI 1.10-5.38, p=0.049) were significantly associated
with shorter survival. Conclusion: Patients developing in-hospital AF differed
from subjects hospitalized for AF with respect to the severity of the clinical
profile and prognosis.
PMID- 28496741
TI - Multi-Electrode Ablation Catheters for AF Ablation: Effective Reality or Elegant
Experiment?
PMID- 28496742
TI - Relationship Between Arrhythmia and Sleep Disordered Breathing.
AB - The association between obstructive sleep apnea (OSA) and cardiovascular disease
is well known. Data from most studies investigating the prevalence of OSA in
atrial fibrillation (AF), and of AF in patients with OSA, have supported the
relationship between these common diseases. In addition, several studies have
shown a detrimental effect of OSA on AF treatment. These reports vary
considerably in methodology, and are particularly diverse in their definitions
and diagnosis of OSA and patient populations studied. Considering these studies
individually while exploring their methodological variations and the range of
results achieved can reinforce the necessity of establishing standards for
performing this important research. Reviewing these studies should en courage
practitioners to reflect on how the methodologies, patients, and outcomes are
relevant to their practices.
PMID- 28496743
TI - Association Between BMI and QoL Improvement in AF Patients Following Catheter
Ablation.
PMID- 28496744
TI - The Estimated Risk of Atrial Fibrillation Related to Alcohol Consumption.
AB - The risk of acute heavy alcohol intake on the development of atrial fibrillation
(AF), aka ?holiday heart syndrome?, has been well-described. However, whether
chronic alcohol intake is also associated with increased risk of AF, or might
even be protective as has been observed with other cardiac conditions, is more
uncertain. A number of studies, from basic science to large cohort studies have
been performed to analyze the association between alcohol and AF. Basic-level
studies have found that alcohol causes changes in tissue electrophysiology, ion
channels, and circulating hormones, which might promote development and
maintenance of AF. Clinical studies have generally shown groups with the highest
regular intake of alcohol to be at increased risk, with no association with more
moderate use. However, these studies have not always accounted for other AF risk
factors, been inconsistent in the assessment and validation of the quantity of
alcohol consumed across populations, and been unable to completely separate
drinking patterns from overall health of participants. As a result, solid
conclusions about a threshold level for ?safe? chronic alcohol intake cannot be
made with regard to AF risk, but it appears to be safe within currently
recommended limits of 1 drink daily for women and 2 for men. In this review, we
discuss these findings, limitations, and conclusions.
PMID- 28496745
TI - The Relationship Between Atrial Fibrillation and Chronic Kidney Disease :
Epidemiologic and Pathophysiologic Considerations for a Dual Epidemic.
AB - : Atrial fibrillation (AF) presently affects over 2 million Americans, and the
magnitude and population burden from AF continues to increase concomitant with
the aging of the U.S. POPULATION: Chronic kidney disease (CKD) is present in 13%
of individuals in the U.S., and the prevalence of CKD is also rapidly increasing.
The increasing population burden of CKD and AF will profoundly affect the
clinical and public health, since CKD and AF are both associated with lower
quality of life, increased hospitalization rates, and a greater risk of heart
failure, stroke, and total mortality. AF and CKD often co-exist, each condition
predisposes to the other, and the co-occurrence of these disorders worsens
prognosis relative to either disease alone. The shared epidemiology of CKD and AF
may be explained by the strong pathophysiologic connections between these
diseases. In order to promote a better understanding of CKD and AF, we have
reviewed their shared epidemiology and pathophysiology and described the natural
history of patients affected by both diseases.
PMID- 28496746
TI - Chronic Kidney Disease and Atrial Fibrillation: A Contemporary Overview.
AB - Chronic kidney disease (CKD) is associated with substantial cardiovascular
morbidity, including myocardial infarction, heart failure and stroke. Similar to
CKD, atrial fibrillation (AF) is a prevalent arrhythmia that increases risk for
both stroke and overall mortality. Recent studies demonstrate that both
prevalence and incidence of AF is higher in patient with versus without renal
impairment and risk for developing AF increases as renal function worsens.
Potential mechanisms for the higher burden of AF in CKD patients include but are
not limited to augmented sympathetic tone, activation of the renin-angiotensin
aldosterone system and myocardial remodeling. Similar to the general population,
AF confers an increased risk for both stroke and overall mortality in the CKD
population. The safety and efficacy of antithrombotic therapy across the spectrum
of CKD remains unknown, however, as patients with advanced renal failure are
frequently excluded from randomized trials. While treatment with vitamin K
antagonists appears to reduce ischemic complications without significant bleeding
harm in patients with mild to moderate CKD and AF, the risk benefit ratio of
anticoagulation among thosewith advanced renal failure on dialysis requires
further investigation. Prospective, randomized trials are war ranted to define
the impact of antithrombotic therapy on reducing stroke risk in patients with
both AF and CKD.
PMID- 28496747
TI - Atrial Fibrillation Associated with Heart Failure, Stroke and Mortality.
AB - Atrial Fibrillation (AF) is the most common arrhythmia in the western world.
Because AF prevalence rises with age and western populations are increasingly
aging, AF has been called a "growing epidemic", especially among older persons,
with social and economic consequences. AF may concur to disability and may
cluster with other co-existing clinical conditions. AF is an independent risk
factor for stroke by increasing the thromboembolic risk profile and is associated
with heart failure severity. Among persons with AF, prevalence of stroke,
coronary heart disease, peripheral artery disease, cognitive impairment and
physical disability is significantly higher. AF is associated with higher risk of
mortality through the association with stroke and heart failure: ischemic strokes
are more severe if AF is present and AF may represent a marker of more severe
heart failure. Independently of other known predictors of mortality, death rates
are almost doubled by AF. AF, therefore, is a considerable source of morbidity
and mortality, is associated with disability, and is a major determinant of
quality of life.
PMID- 28496748
TI - Cost-Effective Medicines for Stroke Prophylaxis in Patients with Atrial
Fibrillation.
AB - Non-valvular atrial fibrillation is the most common arrhythmia encountered in
clinical practice and is associated with substantial healthcare costs. The risk
of thromboembolic stroke is 3-5 times higher in patients with atrial fibrillation
compared with the general population. Until the recent emergence of direct
thrombin (factor IIa) and factor Xa inhibitors, antithrombotic therapy for atrial
fibrillation was achieved with antiplatelet agents or vitamin K antagonists,
which are considered cost-effective strategies when compared to no treatment. Now
newer agents, such as the direct thrombin inhibitor dabigatran, can lower
thromboembolic events and reduce the risk of fatal and intracerebral hemorrhage
compared with warfarin, in addition to eliminating the need for costly
therapeutic monitoring. Multiple analyses have shown that dabigatran, when
compared with warfarin therapy that achieves a time in therapeutic range (TTR)
consistent with previous large-scale trials, is a cost-effective approach to
antithrombotic therapy in atrial fibrillation, ranging from $16,385 to $86,000
per quality-adjust life-year (QALY) gained. It has been shown to be especially
cost-effective (QALY < $50,000) for high stroke-risk patients, those with a
CHADS2 score of > 3 (barring excellent INR control) and for lower-risk patients
with a CHADS2 of 2 but concomitant high risk of hemorrhage. In addition, factor
Xa inhibitors, such as rivaroxaban (recently approved by the Federal Drug
Administration [FDA]) and apixaban, may exhibit the same cost savings as
dabigatran in terms of reduction of bleeding and elimination of therapeutic level
monitoring costs. Going forward, the use of these agents and their role in
thromboembolic stroke prophylaxis will need to be evaluated on a patient-by
patient basis, balancing consideration of the patient?s stroke and bleeding
risks, as well as quality of life post-therapy.
PMID- 28496749
TI - Transient ST Elevation in Vagally Mediated Atrial Fibrillation.
AB - We report a case of vagally mediated atrial fibrillation on a young otherwise
healthy man, with straight type ST-segment elevation in inferolateral leads that
resolved a few hours after restoration of sinus rythm, a phenomenon that has
never been previously reported. Even though no definite conclusion about the
underlying mechanism of the ST-elevation can be made, this effect might probably
be the result of intense parasympathetic tone and could be used to differentiate
the causality.
PMID- 28496750
TI - Atrial Fibrillation in Acute Coronary Syndrome.
AB - Atrial fibrillation (AF) is a common cardiac arrhythmia occurring in an estimated
2.7 to 6.1 million people in the United States. The risk factors for the
development of AF are very similar to those for developing coronary artery
disease, and AF is often associated with acute coronary syndrome (ACS) and acute
myocardial infarction (MI). Overall, AF complicates approximately 10% of acute
infarcts and the incidence rate is comparable between the thrombolytic and
percutaneous coronary intervention (PCI) eras. Prior to widespread use of
thrombolysis, the incidence of AF during acute MI was as high as 18%. Moreover,
AF is a marker for increased long term mortality post infarct. Over the past 20
years, the relative mortality risk for patients with AF post MI has remained
around 2.5 times that for patients without AF. The treatment of AF in the setting
of MI and ACS is similar to without; however there is often an increased urgency
to limiting rapid heart rates which may exacerbate acute ischemia. Cardioversion
and IV amiodarone may be utilized more liberally in this setting than otherwise.
Anticoagulation is usually required both for the treatment of MI and possible
PCI, as well as for cerebral vascular accident prevention from AF-induced
thromboembolism. Often patients require triple-therapy for optimal treatment of
both conditions, and special considerations for bleeding risk must be analyzed.
PMID- 28496752
TI - Atrial Fibrillation, Alcohol, Obesity and more....
PMID- 28496751
TI - Stroke and Death Prediction with the Impact of Vascular Disease in Patients with
Atrial Fibrillation.
AB - Atrial fibrillation (AF) is the most common arrhythmia encountered in the U.S.
and the growing burden of AF has profound health implications due to the
association of AF with an increased risk of stroke, heart failure, and mortality.
AF is a significant risk factor for thromboembolic stroke; and also independently
increases total mortality in patients with and without cardiovascular disease.
Various risk stratification schemes such as CHADS2 and CHA2DS2-VASc have been
implemented in clinical practice to determine the risk of cardio-embolic stroke,
and need for thrombo-prophylaxis in patients with AF. AF is also closely related
to the pathophysiology of other cardiovascular and peripheral vascular disease.
Many patients with AF have associated atherosclerosis given that many risk
factors for atherosclerosis also predispose to AF. Myocardial infarction (MI) is
also closely related to AF and its clinical course is affected by new onset AF.
This review elucidates the impact of AF on major adverse cardiovascular events
and mortality outcomes in relation to stroke, coronary artery disease and
peripheral vascular disease.
PMID- 28496753
TI - Microwave Ablation in Mitral Valve Surgery for Atrial Fibrillation (MAMA).
AB - Objective: Microwave ablation in conjunction with open heart surgery is effective
in restoring sinus rhythm (SR) in patients with atrial fibrillation (AF). In
patients assigned for isolated mitral valve surgery no prospective randomized
trial has reported its efficacy. Methods: 70 patients with longlasting AF where
included from 5 different centres. They were randomly assigned to mitral valve
surgery and atrial microwave ablation or mitral valve surgery alone. Results: Out
of 70 randomized, 66 and 64 patients were available for evaluation at 6 and 12
months. At 12 months SR was restored and preserved in 71.0 % in the ablation
group vs 36.4 % in the control group (P=0.006), corresponding figures at 6 months
was 62.5 % vs 26.5 % (P=0.003). The 30-day mortality rate was 1.4 %, with one
death in the ablation group vs zero deaths in the control group. At 12 months the
mortality rate was 7,1 % (Ablation n=3 vs Control n=2). No significant
differences existed between the groups with regard to the overall rate of serious
adverse events (SAE) during the perioperative period or at the end of the study.
16 % of patients randomized to ablation were on antiarrhytmic drugs compared to 6
% in the control group after 1 year (p=0.22). Conclusion: Microwave ablation of
left and right atrium in conjunction with mitral valve surgery is safe and
effectively restores sinus rhythm in patients with longlasting AF as compared to
mitral valve surgery alone.
PMID- 28496754
TI - Statin and Atrial Fibrilation: When does it work?
AB - In the recent years, some clinical and experimental studies have suggested that
the use of statins may protect against atrial fibrillation (AF). A relation
between inflammation and the development of AF has been described, and the potent
anti-inflammatory and antioxidant properties of statins may make them effective
in preventing the development of AF. A global analysis of the literature suggests
that the use of statins is associated with a decreased risk of incidence or
recurrence of AF in some cases. However, this beneficial effect is not seen for
all types of AF in all the patients. The use of statins seems associated 1) with
a lack of benefit in primary prevention of AF, 2) with a significant but
heterogeneous decreased risk of recurrence of AF in secondary prevention, and 3)
with a very significant and homogeneous reduction for the risk of post operative
AF. An intensive lipid lowering statin regimen does not provide greater
protection against AF. Patients with coronary heart disease are curr ently
treated with statins in most cases, and this may not have an impact on their
treatment. In contrast, it remains to determine more accurately if statins may
bring a significant benefit for some AF patients without any type of established
atherosclerotic disease or with a low risk of atherogenesis. Since it remains
uncertain whether the suppression of AF in these patients is beyond doubt
beneficial, prescribing statins for this purpose alone should not be recommended
at the present time.
PMID- 28496755
TI - Apixaban in patients with Atrial Fibrillation: A Systematic Review.
AB - Atrial fibrillation (AF) is the most common cardiac arrhythmia which increases
the risk of stroke and systemic embolism by 5- fold, it is a major global public
health problem. Stroke is associated with greatest mortality and morbidity in
patients with AF. Strokes associated with AF are especially large and disabling,
and consequently primary prevention is paramount. Antithrombotic therapy is the
mainstay of stroke prevention. Vitamin K antagonists (VKA's) have been the
standard anticoagulants in stroke prophylaxis for patients with AF for decades.
Despite their effectiveness, they are limited by several factors such as narrow
therapeutic index, drug- drug interactions, slow onset and offset of action,
hemorrhage and routine anticoagulation monitoring to maintain therapeutic
international normalized ratio (INR). During recent times, various novel
anticoagulants have been developed to expand the therapeutic option for stroke
prevention. Apixaban is a novel oral anticoagulant which has been developed and
clinically investigated for prevention of stroke in AF patients. This review
discusses the pharmacological properties, results of clinical trials
investigating role of apixaban for prevention of stroke and its future potential
in clinical practice.
PMID- 28496756
TI - Effect of Omega-3 Polyunsaturated Fatty Acid Supplementation in Patients with
Atrial Fibrillation.
AB - : Atrial fibrillation (AF) is the most common sustained atrial arrhythmia
conferring a higher morbidity and mortality. Despite the increasing incidence of
AF; available therapies are far from perfect. Dietary fish oils, containing omega
3 fatty acids, also called polyunsaturated fatty acid [PUFA] have demonstrated
beneficial electrophysiological, autonomic and anti-inflammatory effects on both
atrial and ventricular tissue. Multiple clinical trials, focusing on various
subsets of patients with AF, have studied the role of PUFA and their potential
role in reducing the incidence of this common arrhythmia. While PUFA appears to
have a beneficial effect in the primary prevention of AF in the elderly with
structural heart disease, this benefit has not been universally observed. In the
secondary prevention of AF, PUFA seems to have a greater impact in the reducing
AF in patients with paroxysmal or persistent AF, stages of AF associated with
less atrial fibrosis and negative structural remodeling. However, AF suppression
has not been consistently demonstrated in clinical trials. In patients undergoing
heart surgery, increasing PUFA intake has yielded mixed results in terms of AF
prevention post-operatively; however, increased PUFA has been associated with a
reduction in hospital stay. Therefore recommending the use of PUFA for the
purpose of AF reduction remains controversial. This is in part attributable to
the complexity of AF. Other conflicting variables include: heterogeneous patient
populations studied; variable dosing; duration of follow-up; comorbidities; and,
concomitant pharmacotherapy. This review article reviews in detail available
basic and clinical research studies of fish oil in the treatment of AF, and its
role in the treatment of this common disorder. ABBREVIATIONS: AF=Atrial
fibrillation, CHS=Cardiovascular Health Study,CABG=Coronary artery bypass
surgery, d=Day, DHA=Docosahexaenoic acid, EPA=Eicosapentaenoic acid, ERP=
Effective refractory period, g=Gram, PAF= Paroxysmal atrial fibrillation, PeAF=
Persistent atrial fibrillation PUFA= Polyunsaturated fatty acid.
PMID- 28496758
TI - Remote Magnetic Navigation System Guided Radiofrequency Ablation of Intra Atrial
Reentrant Tachycardia in Corrected Transposition of Great Arteries.
AB - Atrial arrhythmias are delayed manifestations after atrial switch procedures for
d-transposition of the great arteries. Often times, these arrhythmias are
intraatrial reentry tachycardias that arise in the pulmonary venous neo-atrium.
Access and ablation in the pulmonary venous neo-atrium may require baffle
puncture, risking damage to the baffle. We describe a case of neoatrial
arrhythmia ablation in d-transposition of the great arteries using remote
magnetic guided catheter navigation system using a retrograde approach without
doing a baffle puncture.
PMID- 28496757
TI - The Role of Atrial Structural Remodeling in Atrial Fibrillation Ablation:An
Imaging Point of View for Predicting Recurrence.
AB - Atrial fibrillation (AF) is the most common arrhythmia and is associated with a
significant morbidity and mortality. Invasive catheter ablation of AF has emerged
as an effective therapy for patients with symptomatic AF. Atrial remodeling,
particularly structural remodeling, is important not only for AF persistence but
also for AF recurrence after ablation. Atrial dilation and fibrosis are two of
the core processes involved in atrial structural remodeling. Increased
automaticity and triggered activity occur in atrial structural remodeling, which
may cause difficulty in maintaining sinus rhythm after ablation. Furthermore, an
enlarged left atrium (LA) may increase the difficulty in achieving catheter
stability and thereby require more energy to complete AF ablation. AF causes
similar remodeling in both the left and right atria (RA), and myocardial changes
in both atria influence AF recurrence. A non-invasive assessment of fibrotic
structural remodeling helps predict the outcome of AF ablation. A varie ty of
cardiac imaging modalities, such as two- or three-dimensional echocardiography or
multi-detector row computed tomography, have been used to estimate the magnitude
of atrial structural remodeling by measuring atrial volume or LA function.
Furthermore, delayed enhanced cardiac magnetic resonance imaging has been used to
detect not only atrial fibrosis but also the effect of the ablation point. Thus,
atrial remodeling, particularly structural remodeling, plays an important role in
AF recurrence. These non-invasive imaging modalities are significant tools for
estimating atrial enlargement to improve patient selection for AF ablation at the
point of paroxysmal AF, and for estimating atrial fibrosis to select the AF
treatment including ablation strategy at the point of development to persistent
or permanent AF.
PMID- 28496759
TI - Role of Cardiac Imaging (CT/MR) Before and After RF Catheter Ablation in Patients
with Atrial Fibrillation.
AB - Pre-procedure X-ray computed tomography (CT) and magnetic resonance imaging (MRI)
angiography are commonly used to delineate the complex and variable relationship
of the left atrium, pulmonary veins, and surrounding structures. 3D CT and MR
angiography are routinely incorporated into electroanatomic mapping systems to
guide ablation lesion placement in the context of patient specific anatomy. Post
procedure CT and MRI have also proven useful for evaluating complications such as
pulmonary vein stenosis. In the future, these imaging modalities may be used to
visualize more detailed tissue characteristics such as atrial fibrosis and
ablation lesions. This could improve selection of patients for different
treatment strategies and perhaps guide more effective ablation. This review will
discuss current and emerging applications of CT and MRI before and after
radiofrequency catheter ablation of atrial fibrillation.
PMID- 28496760
TI - Post Ablation Left Atrial Tachycardia: Understanding Mechanism, Prevention and
Treatment.
AB - Currently, post-ablation Atrial Tachycardias (ATs) represent a growing clinical
problem particularly in patients with persistent AF undergoing a more extensive
substrate ablation. Understanding mechanisms and location of potentially widely
located arrhythmogenic substrates in the left atrium is crucial for successful
ablation. Mapping and ablation are challenging since complex and multiple ATs may
frequently develop during the index procedure and before conversion to sinus
rhythm. Use of irrigated ablation guided by detailed 3-D electroanatomic
activation maps combined with entrainment pacing is effective with excellent
acute and long-term success rates, rarely requiring multiple procedures.
PMID- 28496761
TI - Should Atrial Fibrillation Burden Be A Feature to Guide Thromboembolism
Prophylaxis?
AB - : Atrial fibrillation (AF) is a well-known risk factor for cerebrovascular events
and systemic emboli. However, the frequency and duration of AF necessary to be
considered at risk for thrombus formation is unknown. This review summarizes the
literature regarding AF burden and risk for thromboembolism. Previously, no
distinction was made between patients who had paroxysmal versus persistent AF in
regards to initiation of anticoagulation. Recently though, given an enhanced
ability to detect even very brief paroxysms of AF via stored device diagnostics,
the issue has been readdressed. However, despite multiple studies no clear
threshold for AF burden to mandate anticoagulation has been established. In
addition, there is a growing body of evidence which suggests that the
pathophysiology of thrombus formation in AF involves mechanisms beyond just
stasis due to protracted episodes of discoordinate atrial contraction. Therefore,
once AF has been diagnosed and the risk-benefit ratio favors anticoagulation,
therapy should be initiated and continued indefinitely unless a bleeding
contraindication develops. ABBREVIATIONS: AF = atrial fibrillation, AT = atrial
tachycardia, LAA = left atrial appendage, PAF = paroxysmal atrial fibrillation,
SE = systemic emboli.
PMID- 28496762
TI - The Use of Ranolazine in the Management of Recurrent Atrial Fibrillation After
Percutaneous Radiofrequency Ablation.
AB - Long-term medical treatment options for atrial fibrillation (AF) include rate
control as well as rhythm-control therapy with various antiarrhythmics. However,
because of the limited efficacy and potential side effects of these medications,
percutaneous and surgical ablations in AF patients have evolved as alternative or
additional approaches to achieve rhythm-control. Nonetheless, arrhythmia
recurrences may also occur after these procedures. Thus, the search for
complementary treatment options continues.Ranolazine possesses antiarrhythmic
effects in atrial myocytes via blockade of sodium channels. These properties
facilitate AF suppression in animal models and human subjects. We report a
patient with persistent AF that was refractory to medical management and
percutaneous catheter ablation. She has remained in sinus rhythm for at least 18
months after the initiation of ranolazine.
PMID- 28496765
TI - The Kansas City Heart Rhythm Symposium.
PMID- 28496763
TI - Primary Prevention of Atrial Fibrillation where are we in 2012?
AB - Drugs to alter or delay myocardial remodelling associated with heart failure,
hypertension, or inflammation in the post-operative setting, may prevent the
development of atrial fibrillation. Current experimental and clinical evidences
support specific treatments for defined patient population (i.e. ACE-inhibitors
and ARB for chronic heart failure and hypertension expecially with LV
hypertrophy; statins, corticosteroids and possibly colchicine after cardiac
surgery).
PMID- 28496764
TI - Echocardiography In the Prediction of Atrial Fibrillation Recurrence: A Review.
AB - Atrial fibrillation (AF) is a very common sustained arrhythmia. Co-morbidities
and age signifi cantly accelerate the progression of AF to persistent and
permanent forms and the development of complications. The rate of AF recurrence
is 10% in the first year after the initial diagnosis (25-50% in the first month
after restoration of sinus rhythm) and about 5% per annum thereafter. Left
ventricular (LV) diastolic dysfunction degree has been associated with new-onset
AF and in the last few years many new parameters to evaluate diastolic function
were introduced and validated, even in patients with AF. Aim of this review was
to summarize echocardiographic parameters, focusing on new tools, to evaluate
patients with AF and to explore the role of echocardiographic evaluation to
predict recurrence of the arrhythmia.
PMID- 28496766
TI - Impact of Atrial Fibrillation on Coronary Blood Flow: A Systematic Review.
AB - Patients with atrial fibrillation (AF) frequently present with symptoms
suggestive of myocardial isch- aemia, even in the absence of significant CAD,
that seem to be attributable to abnormalities of myocardial perfusion and
perfusion reserve. According to the results of recent human and previous
experimen- tal studies the increase in coronary artery blood flow during AF is
smaller, while the coronary vascular resistance during the arrhythmia does not
decrease as much as we would expect, suggesting a mismatch between coronary blood
flow and myocardial metabolic demand. AF itself diminishes coronary flow reserve,
especially in the subendocardial layer, partly as a result of the increase in the
myocardial com- ponent of coronary vascular resistance, and it is possible that
irregular ventricular rhythm may play an important role. The mismatch of coronary
blood flow and myocardial metabolic demand, especially in view of the severe
reduction in coronary flow reserve, may have deleterious consequences that are
not limited to patients with CAD.
PMID- 28496767
TI - Atrial Fibrillation and the Role of LAA in Pathophysiology and Clinical Outcomes?
AB - Left atrial appendage (LAA) is a source of thromboembolism especially in patients
with non valvular atrial fibrillation (AF). It is reasonable to accept LAA as a
distinct part of left atrium (LA) with unique anatomical and physiological
properties. Advances in imaging modalities increased the knowledge about
anatomical and physiological characteristics of LAA. It is important to prevent
the AF patients from systemic thromboembolic events, and new pharmacological and
non pharmacological management approaches demonstrate encouraging results. Also
pulmonary vein isolation which has been accepted as a curative and useful
treatment option for the treatment of drug resistant AF has been helpful in
understanding the electrophysiological properties of LAA. Accumulating data
revealed that LAA continues to be the one of the most important structure of
heart during AF because of its distinctive anatomical, mechanical, and
electrophysiological properties.
PMID- 28496768
TI - Mortality Risk Associated with AF in Myocardial Infarction Patients.
AB - Atrial fibrillation (AF) complicating myocardial infarction (MI) has been a
controversial topic for the last few decades. It has generated a plethora of
debates regarding whether it is a risk indicator of co-morbidities and poor
haemodynamic status or independent causal mediator of poor outcomes. The
management of this condition has also been idiosyncratic probably due to
confusion regarding its prognostic significance. We shall review the literature
and attempt to elucidate the prognostic significance as well as evidence
available for defining management strategies.
PMID- 28496770
TI - Sustained Fibrillation Within the Left Atrial Appendage During Catheter Ablation
for Recurrent Atrial Tachyarrhythmia.
AB - The left atrial appendage (LAA) has recently been recognized as a potential
source of arrhythmia in patients undergoing repeat ablation procedures for atrial
fibrillation (AF). In this case report we describe sustained fibrillation
contained entirely within the LAA, that continued even after electrical isolation
of the LAA was performed. This case supports the concept that in selected
patients with AF, catheter ablation strategies may need to incorporate LAA
isolation to minimize recurrence.
PMID- 28496769
TI - Predictors of Recurrence After Radiofrequency Ablation of Persistent Atrial
Fibrillation.
AB - Radiofrequency catheter ablation that targets the pulmonary veins is well
established as a mainstay for drug-refractory, paroxysmal atrial fibrillation
(AF). However, in patients with persistent AF, the ideal approach remains
elusive. Further, despite the various additional ablation strategies that have
been investigated in patients with persistent AF, the rate of recurrent atrial
tachyarrhythmias after ablation remains relatively high. In this review, the
predictors of recurrent atrial tachyarrhythmias after catheter ablation of
persistent AF will be discussed.
PMID- 28496771
TI - Should Physicians Continue to Recommend Fish Oil for Patients with Atrial
Fibrillation?
AB - Many physicians recommend the use of fish oil or omega-3 polyunsaturated fatty
acids (n-3 PUFA) in atrial fibrillation (AF) patients. N-3 PUFA have demonstrated
anti-fibrillatory properties in several animal studies, however, data regarding
their efficacy in preventing AF in humans have been mixed. This article
critically reviews studies that have investigated the use of n-3 PUFA for the
secondary prevention of paroxysmal and persistent AF and the primary prevention
of post-operative AF. We conclude that n-3 PUFA should no longer be recommended
for use in any of these AF subtypes until more data are available.
PMID- 28496772
TI - The Impact of Atrial Fibrillation Ablation on Quality of Life.
AB - Quality of life (QoL) is a very important endpoint in trials reporting the
efficacy of catheter ablation in patients with atrial fibrillation (AF). It has
been shown that AF ablation significantly improves the QoL, but recent studies
question the usefulness of the most used generic QoL instrument in AF patients.
The complexity of the disease makes it mandatory to employ disease specific
instruments in the assessment of QoL. This paper reviews the current knowledge of
various QoL instruments, including the limitations and pitfalls, and the impact
of AF ablation on the QoL.
PMID- 28496774
TI - Abnormal Left Ventricular Filling and Postoperative Atrial Fibrillation After
Cardiac Surgery.
AB - Objective: Diastolic dysfunction has been associated with the development of
atrial fibrillation (AF) in the community and recently in the postoperative
setting. We hypothesized that abnormal left ventricular filling predicts AF after
cardiac surgery, a common marker of poor outcomes. Methods: Cohort study of 233
consecutive patients, who underwent coronary artery bypass grafting (CABG) and/or
valve surgery. Early and late mitral inflow velocity (E, A) and deceleration time
(DT) and early mitral annular velocity (e?) were obtained from echo within 6
months prior to cardiac surgery. Associations with postoperative AF were studied
with multivariable logistic regression. Results: Postoperative AF occurred in 65
(28%) of patients, who were on average older, more likely to have had prior
episodes of AF, had larger inferior vena cava diameter and shorter DT (189 +/-
62ms vs. 214 +/- 63ms, p=0.007). Multivariable adjusted analyses demonstrated
only DT (odds ratio [OR] 0.65 (95% confidence interval [CI] 0.40-0.97), older age
(OR 2.62 (95% CI 1.68 - 4.10) and prior episodes of atrial fibrillation (OR 7.20,
CI 1.41-36.8) to be independent predictors of postoperative AF. Patients with a
DT <= 200ms (n=117) had a significantly longer length of hospital stay compared
with those who had DT > 200ms (n=116) (median 7 days (interquartile range [IQR] 5
10) vs. 6 days (IQR 5-7, p=0.0002). Conclusion: In patients who undergo cardiac
surgery, a shorter DT of early mitral inflow identified greater risk for
postoperative AF and a longer hospital stay. These results provide useful
information for preoperative risk assessment and mechanistic understanding of
postoperative AF.
PMID- 28496773
TI - Atrial Fibrillation Complicating Acute Coronary Syndromes.
AB - Atrial fibrillation frequently complicates myocardial infarction. Patients with
atrial fibrillation complicating acute coronary syndrome have increased morbidity
and mortality relative to patients that remain in normal sinus rhythm. No studies
have identified a mortality benefit to rhythm control compared with rate control
in the setting of acute coronary syndrome. Stroke prevention should be pursued
with oral anticoagulation therapy, although the majority of patients with atrial
fibrillation associated with acute coronary syndrome receive only antiplatelet
therapy. There are several novel oral anticoagulant therapies now available, but
these agents have not been well studied in combination with dual antiplatelet
therapy. Therefore, warfarin as part of triple therapy is the most conservative
approach until additional data becomes available.
PMID- 28496775
TI - Atrial Fibrillation and Metabolic Syndrome: Understanding the Connection.
AB - Metabolic syndrome, a constellation of conditions including obesity,
dyslipidemia, hypertension and insulin resistance, has increased to epidemic
proportions. Metabolic syndrome has been recognized as a risk factor for
cardiovascular morbidity and is likely related to the epidemic of cardiovascular
diseases. Perhaps not coincidentally, its growth in incidence has paralleled that
of atrial fibrillation. Various components of metabolic syndrome have been known
to have a role in the pathogenesis of atrial fibrillation. With the
conglomeration of components seen in the metabolic syndrome, the risk for atrial
fibrillation increases greatly. Several studies have elucidated the role of
metabolic syndrome in the development of atrial fibrillation. Its role on the
atrial substrate makes it an important determinant of progression of disease and
failure of therapeutic strategies such as catheter ablation. Control of the
various components of metabolic syndrome may ultimately lead to better outcomes
in atrial fibrillation patients.
PMID- 28496776
TI - AF and Venous Thromboembolism - Pathophysiology, Risk Assessment and CHADS-VASc
score.
AB - Atrial fibrillation (AF) and venous thromboembolism (VTE) are the two most common
medical conditions managed with anti-coagulation therapy. Not all the patients
with decreased mobility or AF have a similar risk for thromboembolism. The risk
factors for venous thromboembolism and thromboembolism associated with AF are
described in various studies. Considering that the two conditions have similar
pathophysiologic basis of clot formation, one could imply that the risk factors
for the occurrence of thrombosis could be similar. The present review focuses on
the similarities and differences in the clinical risk factors of VTE and AF
related thromboembolism. We will also be discussing the role of CHADS2-VASc
scoring system in the risk assessment of VTE.
PMID- 28496777
TI - Postoperative Atrial Fibrillation: Year 2011 Review of Predictive and
Preventative Factors of Atrial Fibrillation Post Cardiac Surgery.
AB - Background: Post cardiac surgery atrial fibrillation is common after cardiac
surgery. Despite the advances in medical and surgical treatment, its incidence
remains high and unchanged for decades. The aim of this review was to summarize
studies published in 2011 on identifying factors, prevention strategies,
treatment and effect of post operative atrial fibrillation (POAF) on the outcome
after cardiac surgery. Methods: A review was performed on Medline, Embase and
Chocrane on all of the English-language, peer-reviewed published clinical studies
on POAF; studies investigating the mechanism of developing POAF, prevention,
treatment and outcome were all included and analyzed. Case reports, studies on
persistent/preoperative atrial fibrillation (AF), POAF after cardiac transplant,
congenital cases and nonclinical studies were all excluded. We have also valuated
these studies based on the type of the study, their originality, impact factor of
the journal and their limitations. Results: Overall 62 studies were reviewed and
analyzed; 26 on POAF predictive factors, 31 on preventative strategies and 6 on
the outcome of POAF. Of these studies only two were original and the remaining
were either performed in AF in general population (n=10) or had been studied and
reported several times before in cardiac surgery (n=50). The average impact
factor of the journals that POAF was published in was only 2.8 ranging between
0.5 and 14.5. Conclusion: Post cardiac surgery atrial fibrillation is a multi
factorial and complex condition. Cardiac surgery may be a risk factor for
developing POAF in patients already susceptible to this condition and may not be
a complication of cardiac surgery. Future studies should mainly focus on
histological changes in the conductive tissue of atrium and related treatment
strategies rather than predictive factors of POAF and more funding should be made
available to study this condition from new and entirely different perspectives.
PMID- 28496778
TI - Solutions to Reduce Cardiovascular Events in Patients with Atrial Fibrillation.
AB - AF is the most common sustained cardiac rhythm disorder and an established risk
factor for ischemic stroke. Ischemic strokes which occur in patients with AF are
particularly severe and disabling. In addition, stroke recurrence is more common
in patients with AF compared with those without it. Previous cerebrovascular
events, age, hypertension, diabetes, and heart failure are risk factors for
stroke in patients with AF. Various risk stratification schemes have been
developed to quantify the risk for stroke in patients with AF. Currently, the
most frequently used schemes to assess stroke risk in patients with AF are
CHADS2, the ACC/AHA/ESC and American College of Chest Physicians (ACCP) schemes.
Current risk scores are largely derived from risk factors identified from
clinical trials and many potential risk factors have not been properly
considered. Consequently, the stroke risk in many patients could be
underestimated, and these patients could receive a suboptimal antithrombotic
prophylaxis. There is substantial evidence for the benefit of vitamin K
antagonists (VKA) in preventing stroke and reducing mortality. Novel oral
anticoagulants are available for stroke prevention in patients with AF which
overcome some of the difficulties associated with VKA. The introduction of novel
oral anticoagulants in clinical practice and the advances in identifying patients
at risk of stroke together may overcome many of the difficulties in providing
effective stroke prevention for patients with AF.
PMID- 28496779
TI - Combined Catheter Ablation for Atrial Fibrillation and Watchman(r) Left Atrial
Appendage Occlusion Procedures: A Single Centre Experience.
AB - Background Patients with atrial fibrillation (AF) may be interested in undergoing
concomitant interventions of left atrial catheter ablation and device occlusion
of the left atrial appendage (LAA). We report on the feasibility and outcome of
combined procedures in a single centre case series. Methods Twenty-six patients
underwent either first time or redo pulmonary vein isolation (PVI) procedures
followed by successful implant of a Watchman(r) device. Results All procedures
were uncomplicated with a mean case time of 233 +/- 38 minutes. Maximal LAA
orifice dimension was smaller in 3 of 26 patients post PVI (range 1mm) than on
the pre-procedural transoesophageal echocardiogram (TOE). A new peri-device leak
of maximum 3mm was noted in 5 of 26 patients at 6 week follow-up TOE, but
resolved in 4 by the 6 month follow-up. Conclusion Combined procedures for
catheter ablation for AF and Watchman(r) LAA implant appear to be feasible and
safe with satisfactory occlusion of the LAA maintained at follow-up.
PMID- 28496780
TI - Typical Atrial Flutter - When Do You Say You Have Got It.
PMID- 28496782
TI - Atrial Flutter Ablation Using MediGuideTM Non-fluoroscopic Catheter Tracking
System: A Novel Technology to Reduce Radiation Exposure.
AB - We describe the first case of cardiac arrhythmia ablation with the novel
MediGuideTM non-fluoroscopic catheter tracking system in North America. This new
technology uses electromagnetic field to track sensor integrated intracardiac
electrophysiology catheters which are projected on pre-recorded fluoroscopy cine
loops. This new technology permits catheter tracking in virtual biplane
fluoroscopy and enhances spatial resolution of conventional 3D mapping systems
while drastically reducing radiation exposure.
PMID- 28496781
TI - The Role of Echocardiography as a Predictor of the Incidence and Progression of
Atrial Fibrillation.
AB - Atrial fibrillation is the most frequent sustained arrhythmia and is an
independent risk factor for stroke and death. In recent years, major
echocardiographic advances have been made with the development of new techniques
and applications that can be extremely useful for the management of these
patients. This paper describes the role of echocardiography as a predictor of the
incidence and progression of atrial fibrillation. A detailed description of the
most relevant studies and recognition of unresolved questions regarding this
subject are presented here. A special emphasis will be given on new techniques
that allow the assessment of myocardial deformation and their possible role in
the way we treat these patients.
PMID- 28496783
TI - World Atrial Fibrillation Awareness Day - It's About Time!
PMID- 28496784
TI - Differences of BiAtrial Substrate Properties in Patients with Different Types of
AF.
AB - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in
clinical practice and induces cardiac dysfunction and strokes. The development of
AF requires a"trigger" and also an electroanatomic "substrate" capable of both
initiating and perpetuating AF. Over the past decade, the understanding of the AF
substrate properties in both atria has increased with fractionation and frequency
analyses of the local atrial electrograms using three-dimensional electroanatomic
mapping systems. The purpose of this review was to discuss the differences in the
atrial substrate properties in patients with different types of AF.
PMID- 28496785
TI - Body Mass Index, Quality of Life, and Catheter Ablation in Patients with Atrial
Fibrillation.
AB - Atrial fibrillation and obesity are interlinked epidemics and both impair quality
of life. As the prevalence of both conditions in the US continues to rise, so
will the number of obese patients with atrial fibrillation referred for catheter
ablation. Catheter ablation has already been shown to significantly improve
quality of life in patients with atrial fibrillation. Until recently, there has
been little attention to the effects of catheter ablation on quality of life
specifically in obese patients with atrial fibrillation. This paper will review
what is known about the effects of atrial fibrillation and obesity on quality of
life and how quality of life is affected by catheter ablation for atrial
fibrillation in obese patients.
PMID- 28496786
TI - How Does Alcohol Intake Relate to the Risk of Atrial Fibrillation?
AB - Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. The
close relationship between acute excesses of alcohol and the occurrence of AF
even in healthy individuals has been known for several decades. More recently, a
significant relationship has been consistently observed between elevated
consumption of alcoholic beverages on a regular basis and an increased risk of
developing AF. However, the amount of alcohol needed to confer an increased risk
of AF is rather elevated, approximately two alcoholic beverages per day in women
and four to five alcoholic beverages per day in men, suggesting that on a
population level, alcohol is not a major contributor to the global AF epidemic.
PMID- 28496787
TI - Sarcoidosis Masquerading as Atrial Fibrillation: Interesting Case Discussion as
Well as Recent Advances in Diagnosis and Management of Cardiac Sarcoidosis.
AB - This report presents a case of cardiac sarcoidosis initially manifested with
atrial fibrillation. This behavior is very uncommon in spite of the fact that the
disease is multisystemic, affecting predominantly the lungs. It is emphasized
that the diagnosis of the cardiac involvement is difficult, and when this occurs,
can lead to conducting system disturbances, heart failure or sudden death (SD).
The diagnosis can be made by evaluating the clinical manifestations, the
noninvasive tests like ECG, Holter monitoring, chest radiography, thoracic
computed tomography, magnetic resonance image and positron emission tomography.
In general, sarcoidosis is treated with steroid compounds with good outcome,
mainly when performed in the initial phases of the disease. Other cardiac
manifestations, such as arrhythmias, atrioventricular block or heart failure, are
managed similar to other cardiomyopathies.
PMID- 28496788
TI - Respiratory Cycle-Dependent Atrial Trachycardia; its Unique Characteristics and
Relation with Autonomic Nerve System.
AB - Respiration influences the sinus heart rate, however, little is still known about
the tachyarrhythmias related to respiration. Atrial tachycardia (AT) rarely
emerges during inspiration and it also ceases during expiration. This type of AT
is thus called respiratory cycle-dependent atrial tachycardia (RCAT), and it
demonstrates a centrifugal activation pattern. Based on these peculiar P wave
morphologies, the foci converged either around the right superior pulmonary vein
(RSPV) or inside the superior vena cava where the anterior right ganglionated
plexi (ARGP) is considered to be located. The mechanism of such AT is therefore
thought to be related to the activity of the autonomic system.
PMID- 28496789
TI - Rate Control in Atrial Fibrillation: Avoiding Morbidity.
PMID- 28496790
TI - Interdependent Relationship Between Atrial Fibrillation and Sinus Rhythm at the
Hypothetical Interface of Atrial Fibrillation, Autonomic Tone, Sinoatrial Node
and Inflammation : Analytical Review, Reconsiderations, Speculations and New
Insights.
AB - Underlying mechanisms of atrial fibrillation occurrence and its self
extinguishing remain not completely investigated yet. The role of autonomic tone
and sinoatrial node in the interplay between atrial fibrillation and sinus rhythm
is also not fully understood. The influence of inflammation as a possible source
of arrhythmia and likelihood of its pharmacologic treatment deserves special
attention. These complex issues are important for better understanding of
arrhythmogenesis and rhythm control. Conceptual reconsiderations through the new
insights primarily on the hypothetic basis may delineate new therapeutic and
preventive strategies. The aim of this analytical review was to reinforce the
clinical and laboratory studies regarding the role of: 1) autonomic tone and
sinoatrial node in restitution of sinus rhythm, 2) new concept of ?vibrantly
quiescent stroboscopic tuning? as a matured status of atrial fibrillation being
prepared for its abruption by slight impulse, 3) inflammation in the interplay
between atrial fibrillation and sinus rhythm, 4) anti-inflammation and anti
allergic therapy to prevent and to treat the arrhythmia.
PMID- 28496791
TI - Reversal of Dilated Cardiomyopathy After Successful Radio-Frequency Ablation of
Frequent Atrial Premature Beats, a New Cause for Arrhythmia-Induced
Cardiomyopathy.
AB - Incessant atrial premature beats as a potential cause for tachycardia-induced
cardiomyopathy was suspected in a patient presenting with dilated non-ischemic
cardiomyopathy and severely altered left ventricular ejection fraction. The
elimination of a left atrial focus by percutaneous RF ablation led to
normalization of the clinical status, of atrial and ventricular dimensions and
left ventricular systolic function.
PMID- 28496792
TI - Role of Left Ventricular Diastolic Dysfunction in Predicting Atrial Fibrillation
Recurrence after Successful Electrical Cardioversion.
AB - The role of left ventricular (LV) diastolic dysfunction in predicting atrial
fibrillation (AF) recurrence after successful electrical cardioversion is largely
unknown. Studies suggest that there may be a link between abnormal LV compliance
and the initial development, and recurrence of AF after electrical cardioversion.
Although direct-current cardioversion (DCCV) is a well-established and highly
effective method to convert AF to sinus rhythm, it offers little else beyond
immediate rate control because it does not address the underlying cause of AF.
Preservation of sinus rhythm after successful cardioversion still remains a
challenge for clinicians. Despite the use of antiarrhythmic drugs and serial
cardioversions, the rate of AF recurrence remains high in the first year. Current
evidence suggests that diastolic dysfunction, which is associated with atrial
volume and pressure overload, may be a mechanism underlying the perpetuating
cycle of AF recurrence following successful electrical cardioversion. Diastolic
dysfunction is considered to be a defect in the ability of the myofibrils, which
have shortened against a load in systole to eject blood into the high-pressure
aorta, to rapidly or completely return to their resting length. Consequently, LV
filling is impaired and the non-compliant left ventricle is unable to fill at low
pressures. As a result, left atrial and pulmonary vein pressure rises, and
electrical and structural remodeling of the atrial myocardium ensues, creating a
vulnerable substrate for AF. In this article, we review the current evidence
highlighting the association of LV diastolic dysfunction with AF recurrence after
successful electrical cardioversion and provide an approach to the management of
LV diastolic dysfunction to prevent AF recurrence.
PMID- 28496793
TI - Co-existence of Atrial Fibrillation with Myocardial Infarction - Unhealthy
Combination.
AB - Atrial fibrillation (AF) is the most common arrhythmia with increasing prevalence
and incidence. As our population ages, modern treatment options and decreased
case-fatality of cardiovascular diseases are likely to increase the number of
patients at risk for AF. AF is a frequent co-existing complication ofmyocardial
infarction (MI). The onset of AF in the setting of AMI requires immediate
intervention which should be individualized for each patient. AF associated with
MI influences the in-hospital, medium- and long-term mortality. This brief
review, based on 41 reports published between 1970 and 2011, focuses on incidence
and mortality in patients with AF in MI setting. Possible mechanisms of AF in MI
and treatment options are also discussed.
PMID- 28496794
TI - Operative Technique and Atrial Tachyarrhythmias After Orthotopic Heart
Transplantation.
AB - There is conflicting evidence that operative technique affects the risk of atrial
tachyarrhythmia after orthotopic heart transplantation (OHT). We sought to
determine whether OHT by bicaval (BC) technique is associated with a lower risk
of atrial tachyarrhythmia than biatrial (BA) technique. Consecutive patients who
underwent OHT between 1997 and 2007 at the University of Minnesota were included
in this retrospective cohort study with follow-up through December 31, 2011. We
included 260 OHT recipients (BA, 155; BC, 105). Fifty-nine patients (22.7%)
developed early atrial tachyarrhythmias. The multivariable odds ratio (95%
confidence interval [CI]) of BC technique for early atrial tachyarrhythmias was
0.85 (0.46-1.57), P=0.59. After a median follow-up of 4.9 years, 40 (15.4%)
patients developed late atrial tachyarrhythmias. The multivariable hazard ratio
(HR) (95% CI) of BC technique for late atrial tachyarrhythmias was 0.99 (0.50
1.96), P=0.98. Graft rejection was found to be a multivariate predictor of late
atrial tachyarrhythmias (HR, 2.89; 95% CI, 1.48-5.65; P=0.002). In contrast to
prior reports, we did not find an association between operative technique and
early or late atrial tachyarrhythmias after OHT. Graft rejection is a risk factor
for late atrial tachyarrhythmias after OHT.
PMID- 28496796
TI - Subclinical Hypothyroidism: An Overlooked Cause of Atrial Fibrillation?
PMID- 28496795
TI - Atrial Remodelling : Role in Atrial Fibrillation Ablation.
AB - There have been considerable advances in understanding the relationship of atrial
fibrillation (AF) and atrial remodelling suggesting that remodelling states have
a significant impact on treatment results. Therefore, we reviewed the literature
about the role of atrial remodelling in AF treatment, focussing on AF ablation.
Atrial fibrillatory activity, dominant frequencies (DF), complex fractionated
atrial electrograms (CFAE) as well as function, volume, and fibrosis of the -
especially left - atrium are most important characteristics for electrical,
contractile, and structural remodelling predicting success of AF treatment. In
particular, the results of AF ablation, either using catheter-based or surgical
techniques, predominantly depend on the degree of structural remodelling, namely
dilatation and fibrosis of the left atrium. The available data suggest that
recognizing parameters of remodelling as predictors for AF treatment facilitates
differentiation between patients who may or may not benefit from the procedure
and individualization of AF treatment by adapting lesion sets, by ablating
additional targets, by reducing left atrial size, or by applying extended
pharmacological treatment.
PMID- 28496797
TI - Omega-3 Polyunsaturated Fatty Acid Supplementation: Mechanism and Current
Evidence in Atrial Fibrillation.
AB - Atrial fibrillation (AF) is the most prevalent arrhythmia and is associated with
considerable morbidity and mortality. Available pharmacologic antiarrhythmic
therapies are often ineffective in preventing the recurrence of AF, possibly
because these drugs target a single pathophysiological mechanism. Given their
beneficial effects on ventricular arrhythmias, omega-3 polyunsaturated fatty
acids (n-3 PUFAs) have recently been investigated as possible candidates in the
treatment of supraventricular arrhythmias. In this review, we explore the current
understanding of the antiarrhythmic effects attributed to n-3 PUFAs including
direct modulation of ionic channels, improvement of membrane fluidity, anti
inflammatory and antifibrotic effects, and modulation of sympatho-vagal balance.
We will then focus on the results of epidemiologic studies exploring the
associations between nutritional intake of n3 PUFAs and the incidence of AF, and
will review the findings of the clinical trials investigating the effects of n-3
PUFAs supplementation in the prophylaxis of AF and in the prevention of its
recurrences.
PMID- 28496798
TI - Impact of Atrial Fibrillation On Cardiovascular Mortality in the Setting of
Myocardial Infarction.
AB - Atrial fibrillation (AF) commonly occurs in patient with acute myocardial
infarction (AMI). Potential triggers for AF development in this setting includes
reduced left ventricular function, advanced diastolic dysfunction and mitral
regurgitation leading to elevated left atrial pressures and atrial stretch. Other
triggering mechanisms include inflammation and atrial ischemia. Multiple studies
have shown that AF in patients with is associated with increased mortality.
However, whether AF is a risk marker or a causal mediator of death remains
controversial. There is relative dearth of data with regard to optimal management
of AF in the setting of acute coronary syndromes. Patients with AMI who develop
AF are at increased risk of stroke. However, the issue of the most appropriate
antithrombotic regimens is complex given the need to balance stroke prevention
against recurrent coronary events or stent thrombosis and the risk of bleeding.
Presently, 'triple therapy' consisting of dual antiplatelet agents plus oral
anticoagulants for 3-6 months or longer has been recommended for patients at
moderate-high risk of stroke. Atrial fibrillation (AF), the most common sustained
arrhythmia seen in clinical practice, often coincides with acute myocardial
infarction (AMI), with a reported incidence ranging between 7% and 21%.[1] The
development of atrial fibrillation in the acute phase of AMI may aggravate
ischemia and heart failure, lead to clinical instability and adversely affect
outcome. In the following we will review the pathophysiology, clinical
characteristics and importance, and management of AF occurring in the setting of
AMI.
PMID- 28496799
TI - The 894G Allele of the Endothelial Nitric Oxide Synthase 3 (eNOS) is Associated
with Atrial Fibrillation in Chronic Systolic Heart Failure.
AB - BACKGROUND: Atrial fibrillation (AF) in patients with heart failure signals poor
prognosis. The endothelial nitric oxide synthase (eNOS) enzyme is a key player in
the counterregulation of oxidative stress, which is related in part to AF
pathogenesis. The purpose of this study was to investigate a possible clinical
association in heart failure patients between the presence of exon 7 G894T eNOS
polymorphism, known to result in the Glu298Asp protein variant, and the
occurrence of AF. METHODS: We analyzed the DNA of 344 patients with chronic
systolic heart failure for exon 7 G894T eNOS polymorphism, using PCR. Odds ratios
for AF were calculated for the homo- and heterozygous G-allele G894T variants
relative to the TT variant. RESULTS: Of the 344 patients, 204 (59%) were
homozygous for the G allele, 122 (36%) were heterozygous (GT), and 18 (5%) were
homozygous for the T allele. AF episodes were documented in 73 patients (36%)
with the GG genotype, in 35 (29%) with GT, and in 2 (11%) with TT. The odds ratio
for AF, based on the presence of at least one G allele in the eNOS 894 gene, was
3.96 (95% confidence interval, 1.17-13.56, p=0.04). Having two G alleles
increased the odds ratio to 4.5 (95% confidence interval, 1.0-20.0, p=0.02).
CONCLUSION: Patients with systolic heart failure demonstrate strong correlation
between AF and the presence of a G allele in the exon 7 G894T eNOS genotype.
These findings support the importance of eNOS polymorphism in the pathogenesis of
AF in heart failure patients.
PMID- 28496800
TI - Our Mission Towards Atrial Fibrillation Free World.
PMID- 28496801
TI - 1st International Symposium on Left Atrial Appendage.
PMID- 28496802
TI - Amiodarone Induced Thyrotoxicosis - Fluctuating RVOT and LV Scar VT.
AB - A 61 year old patient with non-ischemic cardiomyopathy and implantable
cardioverter defibrillator presented with multiple shocks for ventricular
tachycardia (VT). EKG revealed monomorphic sustained VT which was left bundle
inferior axis that spontaneously changed into sustained VT which was right bundle
superior axis. This was suggestive of an outflow tract VT transforming into a VT
probably related to reentry from LV scar. The patient was transferred to our
university for VT ablation. However, further investigation revealed amiodarone
induced hyperthyroidism which was the cause of his ventricular tachycardia storm.
Reversible causes of VT should be considered before proceeding with
radiofrequency ablation.
PMID- 28496803
TI - New Stroke Prophylaxis Options in Atrial Fibrillation Patients.
AB - Atrial Fibrillation (AF) is an epidemic that is increasing in size and scope. AF
can have many symptoms and cause a variety of negative health impacts.The most
important health risk of AF is the increased risk of stroke and systemic
thromboembolism.Oral anticoagulation with warfarin has been the gold standard for
stroke risk reduction in AF, but new drugs and treatment strategies for AF are
changing clinical practice. These new advances could offer better tailoring of
treatments to patients with high risk of stroke while reducing the potential
bleeding complications.
PMID- 28496804
TI - Atrial Fibrillation in Patients with Ischemic and Non-Ischemic Left Ventricular
Dysfunction.
AB - Atrial fibrillation (AF) and left ventricular dysfunction (LVD) are increasingly
common clinical problems, affecting millions of people worldwide. It is well
established that the presence of AF portends a poor prognosis in the setting of
both ischemic and non-ischemic LVD, and frequently results in worsening clinical
status. Many clinical studies and trials have attempted to address treatment
options and efficacy; despite this treatment for AF in LVD is still
controversial.
PMID- 28496805
TI - Primary Prevention of Atrial Fibrillation - The Path Untread.
AB - The prevalence and incidence of atrial fibrillation (AF) is on the rapid rise. To
slow down the AF epidemic, effective primary prevention strategies need to be
instituted. Unfortunately, this is an area that has not been well-explored. There
is a multitude of risk factors that predispose to the development of AF. Of
these, the most common from an epidemiologic perspective are advanced age,
hypertension, diabetes, ischemic heart disease, and heart failure. The first-line
pharmacologic therapies for these predisposing conditions (e.g. beta blockers,
renin-angiotensin system inhibitors, statins, and omega-3 fatty acids) appear to
also have potential roles in the primary prevention of AF. Definitive data,
however, is lacking as to efficacy of these drugs for this particular purpose.
Large-scale, high-quality randomized clinical trials on AF primary preventive
strategies are urgently required in order to guide clinical practice. For now,
adherence to the guideline-based therapies of each individual risk factor appears
to be the most reasonable approach for the primary prevention of AF.
PMID- 28496806
TI - Is An Atrial Defibrillator Still An Option In Treating Patients With Atrial
Fibrillation?
AB - Atrial fibrillation (AF) is a common disorder associated with significant
morbidities and presents several challenges for the control of symptoms and
prevention of long-term implications. Atrial defibrillators (ADs), used for
rhythm control in patients with symptoms refractory to medical therapy, can
detect recurrences of the arrhythmia, allow prompt patient-directed treatment,
and have the potential to reduce hospitalizations and improve quality of life.
The efficacy of this form of therapy is highest in patients with paroxysmal AF,
and with the use of a coronary sinus shocking lead. While R-wave synchronized
shocks are a prerequisite for a safe use, the procedure is well tolerated and
usually not associated with long-term psychological side effects. Limitations of
ADs include acute and chronic complications related to cardiac rhythm device
implantation, the requirement in some cases for more than one shock to terminate
AF, the discomfort from shocks, as well as the need for sedation to alleviate
pain from the shocks. With the ever-expanding role of catheter-based therapies
for AF, it seems that the role of ADs in this regard is rather limited.
PMID- 28496807
TI - Prophylactic Antiarrhythmic Drug Therapy in Atrial Fibrillation.
AB - In patients with recurrent atrial fibrillation (AF), the hallmark of treatment
has been the use of antiarrhythmic drugs (AADs). Goals of therapy include
reduction in the frequency and duration of episodes of arrhythmia as well an
emerging goal of reducing mortality and hospitalizations associated with AF.
Safety and efficacy are important factors when choosing an antiarrhythmic drug
for the treatment of AF, hence, if AAD are required for maintenance of sinus
rhythm, their safety profi le, together with individual patient characteristics,
should be of utmost concern. In the next paragraphs we would like to review some
aspects (electrophysiologic effects, metabolism, side effects, current evidence
and indication) of the most commonly used AAD for the management of patients with
AF, following the Vaughan-Williams classification. However, this system is mainly
based on ventricular activity, therefore, and due to its relatively atrial
selective actions, some agents will not readily fit in the Vaughan Williams AAD
classification. For that reason, in the final part of the manuscript, new
promising agents will be reviewed separately.
PMID- 28496809
TI - Catheter Ablation of Long Standing Persistent Atrial Fibrillation: Lessons
Learned.
AB - Atrial fibrillation has evolved from being a novel unproven procedure to being an
important treatment option for patients with symptomatic atrial fibrillation.
Atrial fibrillation ablation is an appropriate treatment option for patients with
symptomatic atrial fibrillation, particularly if they have failed one or more
trials of antiarrhythmic drug therapy. While much has been learned about the
optimal technique and outcomes for catheter ablation of paroxysmal atrial
fibrillation; catheter ablation of atrial fibrillation in patients with long
standing persistent atrial fibrillation remains in its infancy. The following
objectives would be accomplished in this review article. First, we will review
the various ablation strategies, which have been employed and proposed for
ablation of long standing persistent atrial fibrillation. Second, the
methodology, results and outcomes of the major studies were reviewed in detail,
which have reported outcomes of ablation in this patient population. And finally,
some conclusions were drawn regarding where we stand and where the knowledge gaps
remain as we seek to improve ablation outcomes in this population of AF patients.
PMID- 28496808
TI - The Relationship Between Pericardial Fat and Atrial Fibrillation.
AB - Pericardial adiposity is strongly associated with increased cardiovascular risk,
especially for coronary artery disease. However, until 2010 researchers have not
focused on the mechanistic role of pericardial fat in atrial fibrillation (AF)
pathogenesis. Only a limited number of studies have reported on the significant
association between pericardial fat and AF prevalence, and the role of
pericardial fat on AF chronicity and symptom burden remain an ongoing debate.
Several possible mechanisms associating pericardial fat with increased AF
prevalence have been suggested, but no prior studies have definitively elucidated
the precise role of pericardial adiposity on increased AF risk. Currently,
pericardial fat has recently emerged as a new independent AF risk factor. In this
brief review, we discuss several potential mechanisms that might associate
pericardial fat to AF pathogenesis.
PMID- 28496810
TI - Prevention of Stroke by Antithrombotic Therapy in Patients with Atrial
Fibrillation.
AB - Atrial Fibrillation (AF) is the most common clinically significant sustained
cardiac arrhythmia, a major risk factor for strokes whether it is symptomatic or
silent. The older CHADS2 score and the newer CHADS2-VASc are well validated to
determine stroke risk and guide initiation of antithrombotic therapy, but
haemorrhagic risk has to be respected as well, and scores such as HAS-BLED should
be widely used. Old fashioned warfarin became standard of care outperforming
antiplatelets in every trial but novel classes of anticoagulants that overcome
many of warfarin drawbacks have been introduced and are already guideline
recommended regiments. Nevertheless their use poses new questions that have to
been answered in the near future.
PMID- 28496811
TI - The Temporal Relationship Between Atrial Fibrillation and Ischemic Stroke.
AB - It is well established that the presence of atrial fibrillation (AF) is
associated with an increased risk of stroke; however, the precise role that AF
plays in increasing this risk is less well understood. In particular, it is not
fully known whether a temporal relationship between AF and stroke exists. Early
clinical trials in this field were limited by their rudimentary tools for
monitoring of AF recurrences. More recently, studies employing implantable
cardiac rhythm devices have brought greater precision to our ability to
accurately detect and quantify episodes of AF but have been restricted to patient
populations with clinical indications for those types of devices.In the future,
new monitoring modalities such as subcutaneous devices and external patches may
allow us to extend precise arrhythmia monitoring to the broader AF population.
Due to the relatively low rate of clinical events, large clinical trials or
registries will be required to fully appreciate the temporal aspects of AF and
stroke and alternative metrics for quantifying AF recurrences need to be
explored.
PMID- 28496812
TI - Catheter Ablation of Atrial Fibrillation to Maintain Sinus Rhythm.
AB - Catheter ablation of atrial fibrillation (AF) is an important treatment modality
for patients with AF. Although the superiority of catheter ablation of AF over
antiarrhythmic drug therapy has been demonstrated in middle aged patients with
paroxysmal AF, the role of catheter ablation in other patient subgroups,
particularly in the elderly, those with heart failure, and those with long
standing persistent AF has not been as well defined. Furthermore, although AF
ablation can be performed with reasonable efficacy and safety in experienced
hands, late recurrences of AF a year or more following AF ablation are not
uncommon. Fortunately the techniques and tools used for AF ablation continue to
evolve and it is likely that the outcomes of AF ablation will improve further in
the future.
PMID- 28496813
TI - Atrial Fibrillation in Patients with Cardiac Resynchronization Therapy: Clinical
Management and Outcome.
AB - Atrial fibrillation (AF) and heart failure (HF) are two emerging epidemics in the
cardiovascular field and are strictly inter-related since may directly predispose
to each other. Cardiac resynchronization therapy (CRT) has emerged as an
important therapeutic option for selected HF patients with LV dysfunction and
ventricular dyssynchrony. However almost all RCTs demonstrated the CRT
effectiveness in patients in sinus rhythm (SR), including permanent AF among the
exclusion criteria. In patients with paroxysmal or persistent AF strategies for
rhythm control can be applied, but usually with limited efficacy. Furthermore,
rhythm control strategy did not result superior to rate-control in patients with
heart failure. AF ablation in HF patients is usually performed only in selected
centres. In patients with permanent or long-standing AF and a CRT device the
option of AVN ablation offers the advantage of allowing >95% biventricular
pacing. AF implies a harmful increase in thromboembolic risk. Detection of AF in
patients treated with a CRT device is enhanced by device diagnostic capabilities,
that allow detection of episodes of atrial tachyarrythmias, including silent AF.
In these cases decision making on appropriate antithrombotic prophy/laxis has to
consider clinical risk stratification, usually applying CHADS2 and CHA2DS2VASc
scores. In summary, in order to maximise outcome, AF in patients with CRT prompts
the need to appropriately decide on antithromboembolic prophylaxis (according to
risk stratifications), as well as on rate and/or rhythm control strategies, with
the aim to allow constant biventricular pacing. In this perspective, AVN ablation
has an important role since by inducing pace-maker dependency guarantees
continuous biventricular pacing.
PMID- 28496815
TI - The Relationship Between Physical Activity and Risk of Atrial Fibrillation-A
Systematic Review and Meta-Analysis.
AB - Aim: The aim of this systematic literature review and meta-analyses was to
explore the relationship between physical activity and risk of new-onset atrial
fibrillation (AF) or flutter (AFlu). Results: The search revealed 10 published
studies that were eligible for three different meta-analyses. A meta-analysis of
six case-control studies showed that risk of AF increased more than 5-fold in
athletes compared to non-athletic controls, OR=5.3 [(3.6, 7.9; 95% confidence
interval (CI)], p<0.0001. A second meta-analysis of three case-control studies
showed a significantly higher prevalence of athletes among AF populations
compared to their healthy controls, OR=4.7 (3.1-6.9; 95% CI), p<0.0001. A third
meta-analysis of three prospective large-scale long-term studies showed that
moderate/high habitual physical activity was associated with significantly
reduced risk of AF compared with none or very low intensity physical activity
OR=0.89(0.83, 0.96; 95% CI), p=002 Conclusions: Long-term vigorous physical
training or lack of physical activity both are associated with increased risk of
AF, while habitual moderate physical activity may be associated with reduced
risk. Further large-scale prospective randomized controlled studies particularly
in athletes are needed to further confirm these findings.
PMID- 28496814
TI - Impact of Obstructive Sleep Apnea on Outcomes of Catheter Ablation of Atrial
Fibrillation.
AB - : Obstructive sleep apnea (OSA) is a growing epidemic in the United States and
significantly contributes to the increasing prevalence of atrial fibrillation
(AF) in the U.S. POPULATION: Although a strong correlation between OSA and AF has
been demonstrated, a causal relationship between these two conditions has not
been definitively established. Evidence of OSA is an important consideration of
AF management and impacts the success rate of catheter ablation. The presence of
OSA tends to predict a lower success rate and higher complication rate for
catheter ablation of AF. However, recent studies evaluating OSA as an independent
risk predictor of AF recurrence following an ablation procedure have yielded
conflicting results. A greater understanding of these conditions would allow for
a more specific therapy targeting the type of AF associated with OSA. The
following review provides a brief summary of obstructive sleep apnea etiology,
focuses on the relationship between OSA and AF, and discusses the impact of OSA
on the outcomes of catheter ablation of AF.
PMID- 28496816
TI - The Role of Pericardial and Epicardial Fat in Atrial Fibrillation Pathophysiology
and Ablation Outcomes.
AB - Emerging evidence suggests that epicardial and pericardial fat are related to the
presence, severity and outcome of AF. These associations, independent of
generalized obesity, suggest that they may become increasingly useful as markers
for risk stratification or monitoring in the clinical setting. Mechanistically,
studies have suggested the effects of epicardial and pericardial fat may be
mediated by local adipokines, inflammation, fatty infiltration, modulation of AF
drivers and left atrial dilatation. Given the dual epidemics of AF and obesity,
in the present paper we review the role that the ectopic adipose tissue
surrounding the heart has in the pathogenesis of AF. Further inquiries in this
active area of investigation may ultimately lead to new insights in how to best
combat these interrelated epidemics and reduce the societal burden of AF.
PMID- 28496817
TI - Impact of Metabolic Syndrome on Ablation-Outcome in Patients with Atrial
Fibrillation: A Systematic Review.
AB - Metabolic syndrome (MS), a pro-inflammatory state with hypertension, diabetes,
dyslipidemia and obesity is presumed to be a close associate of atrial
fibrillation (AF). However, the exact mechanism by which MS facilitates
perpetuation of AF is yet to be fully understood. Moreover, the impact of the
components of MS as well as MS as a group, on ablation-outcome in AF is not
clearly elucidated until now. This review has compiled the results from major
studies that have looked into those risk factors and defined their significance
in influencing ablation-outcome in AF. It has also overviewed the impact of life
style changes that might improve the success rate of AF-ablation by effectively
addressing the different constituents of MS.
PMID- 28496819
TI - How Much Exercise Is Too Much.
PMID- 28496818
TI - Risk Factors for Post-Coronary Artery Bypass Grafting (CABG) Atrial Fibrillation
and the Role of Aspirin and Beta Blockers in its Prevention.
AB - Background: Atrial fibrillation/flutter (AF) is the most common arrhythmia
following coronary artery bypass grafting (CABG) and it increases morbidity and
mortality associated with this procedure. The purpose of this study was to
evaluate the predictability of this arrhythmia using previously identified risk
factors and to assess the efficacy of recommended prophylactic beta blocker (BB)
therapy in the prevention of post CABG AF. Methods: We performed a retrospective
chart analysis of consecutive patients undergoing elective CABG during 1 year
period. Patients who developed new onset AF after the surgery were designated as
cases and those who did not, as controls. 41 different variables were analyzed
using Chi-square test and independent sample t-test. Multivariate analysis was
carried out using logistic regression model. Results: 23% patients undergoing
CABG developed AF during post-operative period. Statistically significant
differences were observed between the two groups in terms of age, use of peri
operative Aspirin (ASA), current smoking, previous history of AF, left atrial
size, history of congestive heart failure (CHF) and brain natriuretic peptide
(BNP) levels. In terms of prophylactic therapy, preoperative BB did not
independently protect against post CABG AF. On multivariate analysis, only age,
use of ASA and previous history of AF remained as independent predictors of post
CABG AF. Conclusion: In our study population, the use of preoperative BB did not
independently decrease the risk of post-CABGAF. Age, peri-operative ASA use and
previous history of AF remained strong independent predictors of post- operative
AF.
PMID- 28496820
TI - Boston AF Symposium Moves to Orlando !
PMID- 28496821
TI - Emergency Physician Patterns Related to Anticoagulation of Patients with Recent
Onset Atrial Fibrillation and Flutter.
AB - Guidelines strongly recommend long-term anticoagulation with warfarin for
patients with newly recognized AF who have high embolic risk by virtue of a
CHADS2 (Congestive Heart Failure, Hypertension, Age >65, Diabetes, History of
Stroke) score >= 2. The goal of this study was to determine patterns of emergency
department-initiated anticoagulation among eligible patients discharged from
Canadian centers with an episode of recent-onset atrial fibrillation and flutter
(RAFF) and determine if decision-making is driven by the CHADS2 score or other
factors. This was accomplished by examining health records using uniform case
identification and data abstraction as well as centralized quality control; it
was conducted in 8 Canadian university emergency departments over a 12-month
period. Eligible patients for this analysis demonstrated RAFF requiring emergency
management, were not already taking warfarin and were not admitted to hospital.
Univariate analyses were conducted using T-test or Chi-square to select factors
associated with anticoagulation initiation at a significance level of p < 0.15
and multiple logistic regression was employed to evaluate independent predictors
after adjustment for confounders. Among 633 eligible patients, only 21 out of 120
patients (18%) with a CHADS2 score >= 2 received anticoagulation and among 70
patients who were given anticoagulation only 21 (30%) had a CHADS2 score >= 2.
Independent predictors of anticoagulation included age by 10-year strata: (OR =
1.7; 95% CI 1.3 - 2.1), heparin use in the anticoagulation (OR = 9.6; 95% CI 4.9
18.9), a new prescription for metoprolol (OR = 9.6; 95% CI 4.9 - 18.9) and being
referred to cardiology for follow-up (OR = 5.6; 95% CI 2.6 - 12.0). CHADS2 >= 2
doubled the likelihood of being prescribed anticoagulation (OR= 2.0; 95% CI 1.5 -
3.5) but was not an independent predictor. It was thus determined that patients
discharged from the emergency department in this study were not prescribed
anticoagulation in keeping with current recommendations. This practice gap merits
further investigation and may benefit from educational efforts or enhanced
support for anticoagulation use from the emergency department.
PMID- 28496822
TI - Prerequisites for Exploring Predictors of Chronic Atrial Fibrillation Recurrence
After Ablation.
AB - The ablation treatment for the atrial fibrillation extends to the persistent
atrial fibrillation now. However, the cure rate of persistent atrial fibrillation
by Radiofrequency Ablation is lower than paroxysmal atrial fibrillation and we
really want to know is the information that what kind of persistent atrial
fibrillation ablation therapy is effective for. Therefore, it is wished the
predictors of recurrence after the ablation for the persistent atrial
fibrillation is confirmed, but does not yet confirm. The cause that is not
confirmed seems to be present in many factors including the gene which the atrial
fibrillation occurs in and persist, the change of pathology into remodeling
according to progression of atrial fibrillation and strategy of the ablation
corresponding to them. Left atrium diameter, Duration of atrial fibrillation and
Cardiac Function that are involved deeply in atrial muscle and electric
remodeling, and Ablation strategy corresponding to them are considered based on
the conventional report. It can be stated now, however, that persistent atrial
fibrillation patients with some degree (although this "some degree" has not been
clearly defined) of enlarged left atrium diameter, prolonged atrial fibrillation
duration, or decreased cardiac function may also revert to sinus rhythm with
Radiofrequency Ablation, more efficient treatment may be developed in the future
and reversion to sinus rhythm may increase the benefit to patients. In summary,
RF ablation for persistent AF is currently required with further study of the
predictors of recurrence after the ablation for the persistent atrial
fibrillation.
PMID- 28496823
TI - Prediction of Atrial Fibrillation by B-type Natriuretic Peptide.
AB - Background: Although several conditions have been proposed as risk factors
contributing to the incidence of atrial fibrillation, many individuals without
such 'risk factors' also suffer from atrial fibrillation. The present study
tested the hypothesis that the risk of new-onset atrial fibrillation increases
with increasing circulating levels of B-type natriuretic peptide in the general
population. Methods: Participants in our health checkup program without atrial
fibrillation or a history of atrial fibrillation were enrolled (n=10,058, 54.3+/
11.3 years old). After baseline evaluation, subjects were followed up for the
median of 1,791 days with the endpoint being the new onset of atrial
fibrillation. Results: Atrial fibrillation occurred in 53 subjects during the
follow-up period (1.16 per 1,000 person-year). The risk of new-onset atrial
fibrillation increased across the gender-specific quartiles of B-type natriuretic
peptide levels at baseline. In multivariate Cox proportional hazard regression
analysis where B-type natriuretic peptide concentrations were taken as a
continuous variable, B-type natriuretic peptide was a significant predictor of
new onset of atrial fibrillation after adjustment for possible factors (hazard
ratio 5.65 [95% CI 2.63-12.41]). Conclusions: The risk of new onset of atrial
fibrillation increases with increasing B-type natriuretic peptide levels in the
general population. Measurement of B-type natriuretic peptide may improve the
prediction of incident atrial fibrillation.
PMID- 28496824
TI - Dronedarone: Where Does it Fit in the AF Therapeutic Armamentarium?
AB - Dronedarone is a derivative of amiodarone with similar mechanisms of action
(blocking calcium, potassium and sodium channels in addition to having anti
adrenergic effects). Compared to amiodarone it has fewer drug interactions
(though it can interact with all current anticoagulants), more limited risk of
organ toxicity, a much shorter half-life with no need for a loading regimen, but
lower efficacy. Dronedarone is approved for the treatment of atrial fibrillation;
has had limited studies for other arrhythmias; and has no adverse drug-ICD
interactions reported. Clinical trials have resulted in only one dosing regimen
(400 mg bid, to be taken with food) and have demonstrated both rate and rhythm
effects in atrial fibrillation (AF). Dronedarone slows the ventricular response,
can prolong the time to/reduce recurrences of/ reduce progression of AF, and
reduce the incidence of hospitalization in AF patients with risk-prone markers.
However, trials have also revealed an increased risk of mortality and other
adverse cardiovascular outcomes from dronedarone when given to patients in heart
failure. The details of these trials, additional pharmacokinetic and
pharmacodynamic information, and recommendations concerning the use of
dronedarone are provided in the full manuscript that follows.
PMID- 28496825
TI - Ischemic Conditioning and Atrial Fibrillation: Hope for a NewTherapy?
AB - Atrial fibrillation (AF) is the most common sustained arrhythmia.It is
accompanied by both structural and ion channel remodeling which underlie the
propensity to perpetuate AF.The prevalence of AF is expected to increase as
population ages and as more patients survival myocardial infarction. Despite
pharmacological and nonpharmacological (such as ablation) therapies for AF, more
effective therapy is needed. Ischemic or pharmacological conditioning offers a
potential novel approach to patients with AF. This review will focus on the basic
biology of ischemic pre- and postconditioning, patho-physiology of AF,
potentially novel AF treatment approachs based on conditioning, and clinical
situations that may be amenable to a conditioning strategy.
PMID- 28496826
TI - Alternative Therapies in the Treatment of Atrial Fibrillation.
AB - Atrial fibrillation (AF) is the most common clinical arrhythmia and represents a
major social and economic problem. The number of subjects with AF is constantly
increasing as a result of aging and improved survival in several cardiac and non
cardiac diseases. Patients with AF are often symptomatic, have a reduced physical
capacity and are at high risk for thromboembolic events. Moreover, AF is
associated with increased mortality and independent of the management, based
either on rhythm or rate control strategy. The safety and efficacy of most anti
arrhythmic drugs are questionable. Increasing attention has therefore been
addressed to evaluate the possible therapeutic and/or preventive effects of forms
of treatment coming from ancient medical traditions of Far East, like acupuncture
and yoga. In traditional Chinese medicine, acupuncture has been found effective
in managing patients with paroxysmal supraventricular tachycardia. Recently, also
in the Western literature, reports have been published supporting the clinical
efficacy of acupuncture to treat arterial hypertension and to reduce chest pain.
Other studies have evaluated the effects of acupuncture and other methods of
Eastern Medicine, i.e., Qigong, Tai Chi Chuan and Yoga, in the treatment of
cardiac illnesses associated with supraventricular arrhythmias. Two reports on
the effects of acupuncture in preventing or reducing the rate of AF recurrences
in patients with persistent or paroxysmal AF have been recently reported .
Another ancient traditional eastern form of therapy and prevention, i.e., yoga,
has been recently shown to reduce episodes of atrial fibrillation and improve the
symptoms of anxiety and depression often associated with this arrhythmia. Growing
evidence indicates that acupuncture and yoga are safe, without any pro-arrhythmic
effect and with limited cost. All these factors should be considered when
evaluating the efficacy of therapeutic intervention for an epidemic disease such
as AF.
PMID- 28496827
TI - Left Atrial Anatomy in Patients Undergoing Ablation for Atrial Fibrillation.
AB - Background: Left atrial anatomy is highly variable, asymmetric, irregular and
three-dimensionally unique. This variability can affect the outcome of atrial
ablation. A catalog of anatomic varieties may aid patient selection and ablation
approach and provide better tools for left atrial ablation. Methods: We analyzed
computed tomography scans from 514 patients undergoing left atrial ablation.
Images were processed on Advantage Windows with CardEPTM software (GE Healthcare,
Waukesha, WI). Measurements of pulmonary vein (PV) ostial size along the long and
short axes were made using double oblique cuts, and area of the ostia was
calculated. Results: Patients with 2 left (LPV) and 2 right PVs (RPV) (62.6%), 2
LPVs and 3 RPVs (17.3%) and 1 LPV and 2 RPVs (14.2%) made up the three most
common variants. In the 2-LPV/2-RPV anatomy, the ostial size and area of the RPVs
were larger than their corresponding LPVs (p<0.001), and the ostial size and area
of the superior PVs were larger than their corresponding inferior PVs (p<0.001).
In the 2-LPV/3-RPV anatomy, the total area of the RPVs was larger than the total
area of the LPVs (p<0.001). In the 1-LPV/2-RPV anatomy, the ostial size of the
left common PV was larger than either right PV (p<0.007). However, the total area
of the RPVs was larger than the area of the left common PV (p<0.002). The left
common PV was also larger than any of the left veins in any of the other
anatomies. The total PV area between the three most common anatomies was not
significantly different. Conclusions: More than 37% of patients have a left
atrial anatomy other than 2 left and 2 right PVs. This data may help in designing
approaches for left atrial ablation, tailoring the procedure to individual
patients and improving ablation tools.
PMID- 28496828
TI - The Prevalence of Low Left Atrial Appendage Emptying Velocity and Thrombus in
Patients Undergoing Catheter Ablation for Atrial Fibrillation on Uninterrupted
Peri-procedural Warfarin Therapy.
AB - Introduction: The 2012 HRS/EHRA/ECAS guidelines encourage pre-procedural
transesophageal echocardiography (TEE) prior to ablation for atrial fibrillation
(AF), but acknowledge a lack of consensus in patients maintained on therapeutic
warfarin before, during and after the procedure. This is partly because the
incidence of left atrial appendage (LAA) thrombus is so low, that it is hard to
draw clear conclusion regarding the characteristics of patients who develop
thrombus. We hypothesize that the presence of low LAA emptying velocities, which
predisposes to thrombus, and/or thrombus itself can be predicted in patients
undergoing ablation, based upon clinical characteristics and transthoracic
echocardiography (TTE). Methods: In this multicentre study, we undertook TTE and
transesophageal echocardiograms (TEE) in 586 patients (age 59.9+/-0.4 years old,
64.5% male) undergoing catheter ablation for AF who were anticoagulated on
warfarin (target international normalized ratio 2-3.5) for >=3 consecutive weeks
prior to procedure and maintained on warfarin for the procedure. Results: Low
peak LAA emptying velocities (<40cm/s) were identified in 111 (24.7%) patients
and LAA thrombus was identified in 3 patients (0.5%) despite having therapeutic
INRs. The 3 patients with thrombus had LAA emptying velocities of 23, 29 and 31
cm/s. None of the remaining patients had a peri-procedural stroke. Patients with
peak LAA emptying velocities <40cm/s or thrombus on TEE had significantly
(p<0.05) higher CHA2DS2-VASc scores (1.7+/- 0.1 v's 1.4+/-0.1), and were more
likely to have impaired LVSF (odds ratio [95% CI]: 2.66 [1.52-4.66]), a LA
diameter >4.6cm on TTE (2.40 [2.13-5.41]), or persistent AF (2.60 [1.63-4.14])
compared to those with a higher LAA velocity without thrombus. Conclusion: In
patients on uninterrupted warfarin therapy, a CHA2DS2-VASc score >=1 or LA
diameter >4.6cm on TTE identifies 91.5% of those at risk of developing thrombus
with LAA emptying velocity of <40 cm/s and 100% of those with thrombus in our
cohort.
PMID- 28496829
TI - Post-operative Atrial Fibrillation - Pathophysiology, Treatment and Prevention.
AB - Atrial fibrillation occurring after cardiac surgery has been the subject of
intensive research over the past decades. However, the incidence remains high,
despite numerous preventive and treatment strategies. In addition, several
reports show that the impact of post-operative atrial fibrillation (POAF) is
high. It is an independent risk factor for mortality after several years. These
findings make clear that the pathophysiology of POAF is not fully understood and
POAF-associated risks to some extent might be underestimated. On the one hand,
excessive triggers during the acute post operative phase after cardiac surgery
might initiate AF even in atria with low vulnerability. On the other hand, many
patients undergoing surgery have an atrial substrate at the time of operation
promoting AF not only in the post-operative phase but also in the days and weeks
thereafter. Progress in our understanding of the AF mechanisms in general has
provided valuable insights into processes involved in atrial structural
remodeling due to advanced age, hypertension, obesity, and congestive heart
failure. These patient characteristics strongly contribute to cardiac disease,
predict POAF and likely have an impact on the risk of thrombus formation in the
weeks and months after cardiac surgery. For a better understanding of the
mechanisms involved, it is important to not only recognize the occurrence of POAF
by continuous monitoring after surgery, but also to identity the extent of atrial
vulnerability to AF in these patients.
PMID- 28496830
TI - Role of Intracardiac echocardiography in Atrial Fibrillation Ablation.
AB - In the recent years, several new evidences support catheter-based ablation as a
treatment modality of atrial fibrillation (AF). Based on a plenty of different
applications, intracardiac echocardiography (ICE) is now a well-established
technology in complex electrophysiological procedures, in particular in AF
ablation. ICE contributes to improve the efficacy and safety of such procedures
defining the anatomical structures involved in ablation procedures and monitoring
in real time possible complications. In particular ICE allows: a correct
identification of the endocardial structures; a guidance of transseptal puncture;
an assessment of accurate placement of the circular mapping catheter; an indirect
evaluation of evolving lesions during radiofrequency (RF) energy delivery via
visualization of micro and macrobubbles tissue heating; assessment of catheter
contact with cardiac tissues. Recently, also the feasibility of the integration
of electroanatomical mapping (EAM) and intracardiac echocardiography has been
demonstrated, combining accurate real time anatomical information with
electroanatomical data. As a matter of fact, different techniques and ablation
strategies have been developed throughout the years. In the setting of balloon
based ablation systems, recently adopted by an increasing number of centers, ICE
might have a role in the choice of appropriate balloon size and to confirm
accurate occlusion of pulmonary veins. Furthermore, in the era of minimally
fluoroscopic ablation, ICE has successfully provided a contribute in reducing
fluoroscopy time. The purpose of this review is to summarize the current
applications of ICE in catheter based ablation strategies of atrial fibrillation,
focusing-on electronically phased-array ICE.
PMID- 28496831
TI - Role of Atrio-Ventricular Junction Ablation in Symptomatic Atrial Fibrillation
for Optimization of Cardiac Resynchronization Therapy.
AB - Cardiac resynchronization (CRT) therapy is indicated in patients with at least
mildly symptomatic heart failure, left ventricular ejection fraction <=35% and
wide QRS, and has been associated with decreased morbidity and mortality.
Unfortunately, approximately 30% of the patients appropriately selected for
therapy do not respond to CRT. Among the reasons for non-response, atrial
fibrillation (AF) plays a prominent role. AF limits the degree of biventricular
pacing during CRT, not only when the ventricular rate is fast and highly
irregular, but also during periods of of relatively constant rate, by causing
fusion and pseudo-fusion complexes. Importantly, achievement of nearly 100%
biventricular pacing is necessary to derive benefit from CRT. A simple, albeit
irreversible, method to maximize biventricular pacing in patients with AF who are
otherwise eligible for CRT is atrioventricular junction (AVJ) ablation. In this
review, we discuss the role of AVJ ablation in CRT optimization in patients with
AF. The available evidence from observational non-randomized studies suggests
that AVJ ablation in patients with AF qualifying for CRT may offer improvement in
heart failure symptoms, better survival, and better cardiac function. In light of
the inherent limitations of non-randomized studies, further randomized studies
are needed to support this treatment option.
PMID- 28496832
TI - Relationship of Ostial Pulmonary Vein Scar with Reduction in Pulmonary Vein Size
after Radiofrequency Ablation for the Treatment of Atrial Fibrillation: An
Observational Cohort Study.
AB - Background: Radiofrequency (RF) ablation procedures to electrically isolate the
pulmonary veins (PV) from the left atrium are frequently used to treat atrial
fibrillation. We hypothesized that changes in PV size after RF ablation would
correlate with the volume of ostial PV scar as assessed by high resolution late
gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR). Methods:
The study cohort included 23 consecutive subjects. Contrast enhanced PV CMR
angiography and LGE were obtained before and 42 +/- 18 days after RF ablation.
Results: A total of 85 PV were analyzed. Imaging after RF ablation demonstrated a
reduction in PV diameter (22 +/- 7 mm to 21 +/- 6 mm, p = 0.001) and a reduction
in cross-sectional area (CSA) (285 +/- 141 to 246 +/- 110, p < 0.001). There was
a significant correlation of PV ostial normalized scar volume with the change in
PV diameter (r =-0.21, p =0.049) and CSA (r =-0.28, p =0.010) after AF ablation.
PV in the highest quartile for PV scar had the greatest reduction in diameter and
CSA (p <0.05 for both). Conclusion: PV size decreases significantly after RF
ablation for the treatment of AF. The change in PV size is linearly related to
the quantity of LGE scar at the PV ostium.
PMID- 28496833
TI - Myocardial Ischemia as a Genuine Cause Responsible for the Organization and
"Fertilization" of Conflictogenic Atrial Fibrillation:New Conceptual Insights
Into Arrhythmogenicity.
AB - Atrial fibrillation continues to be a challenging arrhythmia. There are some
conventional, time-tested explanations of atrial fibrillation genesis, however
some uncertainty of its complete understanding still exists. We focused on atrial
ischemia which, hypothetically, could be responsible for manifestation of the
arrhythmia, irrespective of the underlying heart disease. Evidences abounds that
atrial fibrillation has an extremely strong association with
nutritional/oxidative status of myocardium. This arrhythmia seemingly may stem
from the electrophysiological differences taking place in the boundary areas. To
validate such assumptions we have surveyed widely accepted theories based on
clinical and experimental evidence. There was an attempt to integrate some well
known theoretical explanations (focal, multifocal, ectopic, reentrant activity,
atrial remodeling, etc.) into a new conceptually systematized arrhythmogenesis.
Confronting ischemic and non-ischemic atrial zones electrophysiologically on
their borderlines presumably creates a substrate vulnerable to the development of
atrial fibrillation. The behavior of these interrelated areas is likely ischemia
dependent; the separating borderline(s) may be treated as conflictogenic,
releasing triggers/drivers to commence and to perpetuate the arrhythmia.
Ischemically damaged and non-damaged myocardial areas likely participate in the
relay-race carousel of arrhythmogenicity due to their mutual interactions,
accompanied by the "fireworks" at the separating borderlines. It could be
concluded that myocardial ischemia as a nonspecific proarrhythmic factor
presumably plays a key role in the genesis and sustenance of atrial fibrillation.
Theoretically the most important step in eradication of arrhythmogenic substrate
might be an overall abolition of ischemia regardless of the characteristics of
underlying heart disease. Innovative intellectual and explorative research is
needed to render innocuous the ischemia that might help us win the century's
cardioarrhythmological battle.
PMID- 28496836
TI - Cryo-Balloon Ablation of the Right Superior Pulmonary Vein Involving the Anterior
Right Ganglionated Plexus for Speech and Breathing Induced Atrial Tachycardia.
AB - Targeting ganglionated plexi (GP) during catheter ablation of atrial fibrillation
(AF) is associated with improved outcome. We present a patient with speech and
breathing induced atrial tachycardia (AT) originating in the superior vena cava
(SVC) and the right superior pulmonary vein (RSPV), near the anatomical location
of the anterior right GP (ARGP). The trigger for the arrhythmia appeared to be
vagal discharge from the GP, possibly induced by local stretch. Ablation with a
28 mm cryo-balloon advanced to the RSPV orifice through a patent foramen ovale
(PFO) abolished the arrhythmia, probably involving the underlying parasympathetic
influx to the SVC and RSPV myocardial sleeves.
PMID- 28496834
TI - Age-Dependent Impact of Fluoroscopic Radiation on the Gender of Off-Spring: An
International Survey of Cardiologists.
AB - Background: Fluoroscopic radiation has been implicated in reducing the sex ratio
(M:F) by potentially damaging the Y chromosome. We examined the effects of
exposure to fluoroscopic radiation on gender of offspring of cardiologists across
the world. Methods: An internet based survey was e-mailed worldwide to 8000
physicians who practice invasive electrophysiology and/or interventional
cardiology. Survey questions included age, race, sub-specialty, hours of exposure
to radiation, number of children, gender of off-spring, miscarriages and
mutations and exposure to radiation prior to conception of each child. Logistic
regression analyses were performed on years of exposure and gender of offspring
born post radiation exposure. Results: Responses of 377 cardiologists (84% male
and 16% female) were reviewed. With a total of 398 males and 402 females born to
377 cardiologists, although reduced, the overall sex ratio (0.99) was not
significantly different from that observed in the general population (1.05).
Univariate logistic regression analysis identified higher male births with
increasing hours of radiation exposure (OR 1.034, CI 1.003-1.067 p=0.03) and
increasing paternal age (OR 1.05, CI 1.01-1.08, p=0.002). Subgroup analysis of
children of male cardiologists revealed higher incidence of male births with
increasing age and radiation exposure and multivariate analysis only identified
paternal age as predictor of higher incidence of male births (OR 1.05, CI 1.01
1.089, p=0.0027). Conclusion: Exposure to ionizing radiation leads to a decrease
in the sex ratio (M/F) in younger male cardiologists, while this effect is
reversed with greater number of male births in older male cardiologists.
PMID- 28496835
TI - Left Atrial Fibrosis: Role in Atrial Fibrillation Pathophysiology and Treatment
Outcomes.
AB - The mechanisms of atrial fibrillation are complex, and have been the subject of
intensive study for over fifty years. There is likely a complex interplay between
triggers and substrate that mediates the initiation and maintenance of AF.
Increasingly, atrial fibrosis has been recognized as a key component of that
substrate, playing a critical role in conduction abnormalities in the left atrium
that appear necessary to maintaining AF. In the last several years, our abilities
to quantify left atrial fibrosis - both through catheter- and MRI-based
techniques - has shed important light on the underlying mechanisms of AF, and on
therapeutic strategies to treat AF. Whether our increased appreciation of the
role of atrial fibrosis in AF translates into improved efficacy of catheter
ablation or anti-arrhythmic therapy, though, remains to be seen. The aim of this
review is to summarize clinical investigations of atrial fibrosis as a factor in
the development and treatment of atrial fibrillation.
PMID- 28496838
TI - Why we Should Not Delay Ablation in New Onset Recurrent Atrial Fibrillation.
AB - Recurrent episodes of atrial fibrillation are associated with progressive left
atrial substrate remodelling over time. We present an argument for early ablation
in the treatment of recurrent paroxysmal atrial fibrillation prior to such
deleterious changes in "left atrial electrical health".
PMID- 28496837
TI - Collateral Damage from Catheter Ablation of Atrial Fibrillation Lessons Learnt in
the Past Decade.
AB - Catheter ablation for atrial fibrillation (AF) has been increasingly performed
over the past decade. Regardless of technological advances and technique
improvement, catheter ablation for AF remains a highly complex procedure and the
risk of procedural complications is not negligible. This article discusses the
management and the approach to avoid the serious complications of catheter AF
ablation including pulmonary vein stenosis, atrioesophageal fistula, cardiac
tamponade, stroke and collateral nervous damage. The management of periprocedural
anticoagulation and the complications associated with epicardial AF ablation are
also described.
PMID- 28496840
TI - Atrial Fibrillation Associated Costs for Stroke Hospitalizations of Medicare
Beneficiaries in the Stroke Belt of the United States.
AB - Purpose: To estimate atrial fibrillation (AF)-associated costs for stroke
hospitalizations among Medicare beneficiaries aged >=65 years in a 11-state
region called stroke belt in the United States. Methods: Using the 2010 Medicare
Provider Analysis and Review File database, we analyzed costs of stroke
hospitalizations, conditional on presence of AF (n=226 289) after excluding those
with subarachnoid hemorrhage, no information on race, or a length of stay [LOS]
of 30 or more days. We employed regression analysis to estimate for defined
subgroups the impact of AF on costs while controlling for major potential
confounders. Results: The average cost of all stroke hospitalizations was $27
915. The presence of AF increased this cost by $2711 (9.4%; P<0.001). AF
associated costs were $3159, $2610, and $2197 for patients aged 65-74, 75-84, and
>=85 years, respectively (all P<0.001). Among hospitalization with a length of
stay (LOS) of 14-29 days, AF increased the costs by $5888 (P<0.001). AF was not
associated with higher costs for hospitalizations involving intracerebral
hemorrhage. Conclusions: The costs of stroke hospitalizations are high, and they
are even higher if the patient has AF. Further information is needed on the costs
in patients with AF who are taking anticoagulants.
PMID- 28496839
TI - Role of Stress in Cardiac Arrhythmias.
AB - Stress is a major trigger of cardiac arrhythmias; it exerts profound effects on
electrophysiology of the cardiomyocytes and the cardiac rhythm. Psychological and
physiological stressors impact the cardiovascular system through the autonomic
nervous system (ANS). While stressors vary, properties of the stress response at
the level of cardiovascular system (collectively referred to as the autonomic
cardiovascular responses) are similar and can be studied independently from the
properties of specific stressors. Here, we will review the clinical and
experimental evidence linking common stressors and atrial arrhythmias.
Specifically, we will describe the impact of psychological and circadian
stressors on ANS activity and arrhythmogenesis. We will also review studies
examining relationships between autonomic cardiovascular responses and cardiac
arrhythmias in ambulatory and laboratory settings.
PMID- 28496841
TI - Three-Dimensional Transoesophageal Echocardiography in Electrophysiology
Laboratory.
AB - Percutaneous electrophysiological interventions such as atrial fibrillation and
ventricular tachycardia ablation are usually monitored by fluoroscopy and
electroanatomical mapping systems. Electroanatomical mapping systems lacks soft
tissue contrast and adequate visualization of the target area such as right
ventricular out-flow tract and left atrium. Recently, real-time 3D
transoesophageal echocardiography (RT-3D TEE) has emerged as an important method
for visualizing cardiac structures such as left atrium, left atrial appendix,
interatrial septum, pulmonary veins, Marshall ligament and mitral valve annulus
during invasive procedures. This review aims to describe the RT-3D TEE for the
guidance of percutaneous interventional electrophysiological study especially at
atrial fibrillation in the cardiac electrophysiology laboratory.
PMID- 28496842
TI - Cerebral Embolization During AF Ablation -Pathophysiology, Prevention and
Management.
AB - Catheter based ablation therapy has evolved as an invaluable tool in the
management of symptomatic patients with atrial fibrillation (AF). The procedure
of AF ablation requires instrumentation in the systemic circulation predisposing
to various concerns that can result in systemic embolization. We will describe
the reported incidence of these events and refer to the various pathophysiologic
explanations for their occurrence. Details on the risk factors and the relevant
studies will also be reviewed. Preventive and treatment strategies in patients
undergoing the ablation procedure will be discussed.
PMID- 28496843
TI - Exploring the New Frontiers in the Left Atrial Appendage.
PMID- 28496844
TI - Contrast Induced Thyrotoxicosis in a Patient with New onset Atrial Fibrillation:
A Case Report and Review.
AB - The development of thyrotoxicosis following the administration of iodinated
contrast is a rare occurrence. The effect, referred to as the Jod-Basedow effect,
is often observed in patients with underlying thyroid disease who develop
thyrotoxicosis subsequent to the exposure of exogenous iodide. An example of an
iatrogenic cause for this event may be seen when a large iodide load is given
intravenously for studies or procedures. Thyrotoxicosis can also lead to cardiac
arrhythmias including atrial fibrillation. This is a case presentation of a 74
year old female who developed thyrotoxicosis as well as new onset atrial
fibrillation approximately one week after receiving iodinated contrast dye for a
diagnostic CT of the abdomen. We further review the prior published literature in
regard to atrial fibrillation and thyrotoxicosis.
PMID- 28496845
TI - Atrial Fibrillation Ablation in A Patient with Absent Pericardium.
AB - A 45-year-old woman with drug-refractory paroxysmal atrial fibrillation (AF)
underwent AF ablation. She had a history of abnormal chest radiograph, which on
review was consistent with congenital absence of pericardium and this was later
confirmed on cardiac magnetic resonance imaging. She had extreme leftward and
posterior rotation of the heart, resulting in abnormal fluoroscopic appearance of
the electrophysiological catheters and orientation of the interatrial septum.
This along with exaggerated beat to beat motion of the heart posed significant
technical challenges for the electrophysiologist during left atrial access and
pulmonary vein isolation.
PMID- 28496846
TI - Role of Cardiac Imaging for Catheter-based Left Atrial Appendage Closure.
AB - Thromboembolic stroke is the most serious complication in patients suffering from
Atrial Fibrillation. Atrial thrombi have a predilection to form in the left
atrial appendage. Accordingly, oral anticoagulation is recommended for patients
with high risk of stroke. However, it is widely underused and problems of
compliance are associated with serious risk of bleeding or inefficacy. In these
patients with non-valvular atrial fibrillation, percutaneous occlusion of the
left atrial appendage might help to reduce the risk of thromboembolism. Cardiac
imaging plays a crucial role at all stages of this procedure and trans-esophageal
echocardiography represents the current gold-standard for the assessment of the
left atrial appendage. Cardiac imaging is mandatory to precisely determine the
left atrial appendage anatomy and to select the appropriate size for the device.
Finally, real time three-dimension echocardiography is a powerful additional tool
that improves the safety profile of the procedure. 3D-transoesophageal
echocardiography allows for the accurate assessment of left atrial appendage
anatomy and helps determine if it's suitable for device implantation. Finally, it
also allows for continuous visualization of all intracardiac devices and
catheters during the procedure, and the clear delineation of device positioning
in the left atrial appendage.
PMID- 28496847
TI - CHADS2 and CHA2DS2Vasc-Score in Peripheral Systemic Embolism.
AB - Objectives: We analysed the characteristics of patients with an acute peripheral
embolic event considering the possible use of the CHADS2-Score and the
CHA2DS2Vasc-Score Patients and Methods: We retrospectively analyzed 163 cases of
acute peripheral arterial embolism treated in the Department of Vascular Medicine
of the HELIOS Klinik Krefeld, Germany, from 2008 to 2011. We retrospectively
screened the medical form for information regarding atrail fibrillation (AF) and
the risk factors necessary to calculate the CHADS2 and CHA2DS2vasc score.
Results: Arterial hypertension and age > 75 years were the most frequent risk
factors. Mean CHADS2 score was similar in males and females (2.3 +/- 1.5 and 2.3
+/- 1.4). 66% of the males and 63.3% of the females scored 2 and more points.
Mean CHA2DS2Vasc score was 3.6 +/- 2.0 in males and 4.6 +/- 1.9 in females. 85.2%
of the males and 95.4% of the females scored more than 2 points. In the medical
forms AF was documented in 79 (48%) patients, of which 23 (43 %) were males and
56 (51%) females. Mean CHADS2 score and mean CHA2DS2Vasc score were slightly
higher in those with AF compared to the total group, but not significantly
different. The rate of patients with 2 and more points increased for both scores:
CHADS2 score: males 82.6% and females 76.8%, CHA2DS2Vasc: males 100% and females
98.2%. Almost half of the patients with AF had had anticoagulation with
phenprocoumon before (males 12 (52%), females 24 (43%), but only every 10th was
within the therapeutic range (INR >=2) Conclusion: The number of those with AF is
high amongst patients with acute peripheral embolism. According to the CHADS2 and
CHA2DS2Vasc score, most of these patients had an indication for oral
anticoagulation independent form the embolic event.
PMID- 28496848
TI - Surgery for Atrial Fibrillation: Selecting the Procedure for the Patient.
AB - This manuscript aims to review the current knowledge in the field of surgical
ablation of atrial fibrillation (AF), including a brief discussion regarding the
standard Maze procedure, its variants, minimally invasive thoracoscopic
procedures and hybrid treatments, which briefly summarizes the advantages and
differences between each technique. The rationale for the surgical approach of
the left atrial appendage, its different techniques and complications will also
be briefly covered. To conclude, the current Expert Consensus recommendations
will be reviewed and an algorithm for the surgical management of the patient with
AF, suggesting which technique applies better to which patient, under specific
settings, will also be proposed.
PMID- 28496851
TI - Age as a Risk Factor for Stroke in Atrial Fibrillation Patients: Implications in
Thromboprophylaxis in the Era of Novel Oral Anticoagulants.
AB - Atrial fibrillation is associated with significant morbidity and mortality. There
is a strong relationship between atrial fibrillation and aging, thromboembolism,
stroke, congestive heart failure and hypertension. In addition, advanced age is a
powerful risk factor for stroke and thromboembolism in patients with atrial
fibrillation. For many years, vitamin K antagonists were the only approved
anticoagulants for the management of atrial fibrillation. Lately new
anticoagulants made their appearance and large trials have already shown their
superiority against vitamin K antagonists. Since the arrhythmia is encountered
frequently in the elderly, it is crucial to identify the beneficial effects of
the novel oral anticoagulants in this particular patient population.
PMID- 28496849
TI - Atrial Fibrillation and Heart Failure: A Review of the Intersection of Two
Cardiac Epidemics.
AB - Atrial fibrillation and heart failure are closely linked cardiac conditions that
are both increasing in prevalence due to shared risk factors and common disease
mechanisms. The presence of both disease entities portends an increase in
morbidity and mortality. There are significant similarities in the treatment
strategies of these conditions, and the adequate management of one disease may
prevent the development of the other. To this date, a rhythm control strategy,
even in the heart failure population, has not been proven to be superior to a
rate control strategy. This may in large be due to study design coupled with
deleterious effects of antiarrhythmic agents. There have been considerable
advances over the past decade in catheter and device based management of atrial
fibrillation and studies aimed to examine their long-term effect in patients with
heart failure are underway.
PMID- 28496850
TI - Hybrid Therapy for Atrial Fibrillation: where the Knife meets the Catheter.
AB - During the past decades there has been a consistent evolution of both surgical
and catheter-based techniques for the treatment of stand-alone atrial
fibrillation, as alternatives or in combination with anti-arrhythmic drugs.
Transcatheter ablation has significantly improved outcomes, despite often
requiring multiple procedures and with limited success rates especially in
presence of persistent atrial fibrillation. Surgical procedures have dramatically
evolved from the original cut-and-sew Maze operation, allowing nowadays for
closed-chest epicardial ablations on the beating heart. Recently, the concept of
a close collaboration between the cardiac surgeon and the electrophysiologist has
emerged as an intriguing option in order to overcome the drawbacks and suboptimal
results of both techniques; therefore, the hybrid approach has been proposed as a
potentially more successful strategy, allowing for a patient-tailored
therapeutical approach. We reviewed the recent advancements either from the
transcatheter and surgical standpoint, with a peculiar focus on the current
option to merge both techniques along with an up-to-date review of the
preliminary clinical experiences with the hybrid, surgical-transcatheter
treatment of stand-alone atrial fibrillation.
PMID- 28496852
TI - Rate Control in Atrial Fibrillation: Methods for Assessment, Targets for
Ventricular Rate during AF, and Clinical Relevance for Device Therapy.
AB - Rate control is a widely used treatment strategy for management of patients with
atrial fibrillation (AF). Multiple studies have shown that pharmacologic rate
control is as effective as pharmacologic rhythm control for management of AF. A
snapshot ECG or intermittent monitoring using Holters is the most widely used
technique for assessing ventricular rate during AF. Patients with implantable
devices, such as pacemakers, implantable cardioverter defibrillators, cardiac
resynchronization therapy devices, and implantable loop recorders provide the
ability for continuous long term monitoring of AF and ventricular rate during AF.
It has been shown that continuous monitoring of AF and ventricular rate during AF
by implantable devices is the most comprehensive method for assessment of AF
occurrence and poor rate control, particularly in patients with paroxysmal and
asymptomatic AF. Rapid ventricular rate during AF, as assessed by implantable
devices, has been shown to cause reduction in cardiac resynchronization therapy,
predict inappropriate defibrillation therapy, and identify increased risk for
cardiovascular hospitalizations. The ventricular rate targets for achieving good
rate control during AF depend on the patient characteristics with stricter
targets recommended for patient with compromised functional capacity, such as
patients with HF. Thus it can be hypothesized that timely intervention based on
continuous assessment of AF and poor rate control, with ventricular rate targets
defined based on cardiovascular disease state, may improve clinical outcomes in
patients with AF.
PMID- 28496853
TI - Thinking outside the Box: Rotor Modulation in the Treatment of Atrial
Fibrillation.
AB - Ablation for atrial fibrillation (AF) is an important and exciting therapy whose
results remain suboptimal. Although most clinical trials show that ablation
eliminates AF more effectively than medications, it is disappointing that the
continued single procedural success remains ~50% despite the substantial advances
that have taken place in imaging, catheter positioning and energy delivery. Focal
impulse and rotor modulation (FIRM), on the other hand, offers the opportunity to
precisely define and then ablate patient-specific sustaining mechanisms for AF,
rather than trying to eliminate all possible AF triggers. For over a decade,
electrophysiologists have described cases in which AF terminates after only
limited ablation - usually that cannot be explained by 'random' meandering
wavelets. Indeed, recent studies from several laboratories show that all forms of
clinical AF are typically 'driven' by stable electrical rotors and focal sources,
not by multiple meandering waves. FIRM mapping enables an operator to place a
catheter at typically 1-3 predicted sites in the atria, and with <5-10 minutes of
RF ablation, terminate AF and potentially render it non-inducible. Several
independent laboratories have now shown that such FIRM ablation alone can
terminate or substantially slow AF in >80% of patients with persistent and
paroxysmal AF and increase the single procedure rate of AF elimination from 50%
with PV isolation alone to >80%. Ongoing studies hint that FIRM only ablation,
enabling ablation times in the range observed for typical atrial flutter, may
also achieve these high success rates without subsequent trigger ablation. This
review summarizes the current state-of-the-art on FIRM mapping and ablation.
PMID- 28496854
TI - Sleep Disordered Breathing and the Pathogenesis of Atrial Fibrillation.
AB - This review illustrates the importance of sleep disordered breathing in evolution
and progression of atrial fibrillation. While in early years associations were
mainly attributed to the impact of hypoxemia and hypertension, nowadays multiple,
additional pathways have been investigated or are currently under investigation.
Sleep disordered breathing has been shown to have a direct impact on mechanical
and electrical remodeling. In addition hypercapnia and negative intrathoracic
pressure seem to alter atrial electrophysiology. Finally, impacts on inflammation
and metabolic dysregulation display the complex interplay between breathing
disorders and evolution and progression of atrial fibrillation.
PMID- 28496855
TI - Pharmacological Therapy in Stroke Prophylaxis - The New versus the Old Agents.
AB - Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in
clinical practice. AF is a potent risk factor for stroke and systemic
thromboembolism. Patients with AF have been observed to have a worse outcome
following stroke, therefore prevention of stroke in patients with AF is of
paramount importance. Antithrombotic therapy is crucial for prevention of stroke
in patients with AF. Vitamin K antagonists (VKAs) have been the traditional
anticoagulants for prevention of stroke in patients with AF. Drug treatment with
VKAs is associated with significant management issues, such as an unpredictable
dose response necessitating dose adjustments, frequent laboratory monitoring and
multiple interactions with other drugs. Despite following best practices, VKAs
are associated with limited efficacy and increased risk of hemorrhage. Due to
these limitations a significant effort has been devoted towards development of
newer anticoagulants. Dabigatran, Rivaroxaban, and more recently Apixaban have
been approved by the F.D.A. for the prevention of stroke in patients with AF.
These newer agents possess highly predictable pharmacokinetic and
pharmacodynamics properties which allow a fixed dosing regimen and also eliminate
the need of routine laboratory monitoring. This review discusses various
anticoagulants for prevention of stroke in patients with AF.
PMID- 28496856
TI - Do Omega-3 Fatty Acids Decrease the Incidence of Atrial Fibrillation?
AB - Although atrial fibrillation is a very common medical problem in general
population and has a high incidence in the setting of open heart surgery, there
are very few therapies to prevent occurrence or recurrence of atrial
fibrillation. N-3 polyunsaturated fatty acids have been shown to change basic
physiologic properties of the atrial tissue to make it less susceptible to atrial
fibrillation. In this review, we first describe basic physiological mechanisms
thought to be responsible for these changes and then discuss observational and
interventional studies evaluating the use n-3 polyunsaturated fatty acids for
primary and secondary prevention of atrial fibrillation in the general
population, in subjects undergoing open heart surgery, and in special subgroups
of patients.
PMID- 28496857
TI - Catheter Ablation of Atrial Fibrillation in Patients with Hardware in the Heart -
Septal Closure Devices, Mechanical Valves and More.
AB - Patients with mechanical "hardware" in the heart, such as those with mechanical
cardiac valves or atrial septal closure devices, represent a population at high
risk of developing AF. Catheter ablation of AF in these subjects might represent
a challenge, due to the perceived higher risk of complications associated with
the presence of intracardiac mechanical devices. Accordingly, such patients were
excluded or poorly represented in major trials proving the benefit of catheter
ablation for the rhythm-control of AF. However, recent evidence supports the
concept that catheter ablation procedures might be equally effective in these
patients, without a significant increase in the risk of procedural complications.
This review will summarize the current state-of-the-art on catheter ablation of
AF in patients with mechanical "hardware" in the heart.
PMID- 28496858
TI - Comparing Antiarrhythmic Drugs and Catheter Ablation for Treatment of Atrial
Fibrillation.
AB - In the past years, catheter ablation has evolved into an effective treatment
option for symptomatic, drug-resistant atrial fibrillation (AF) and it has
recently been implemented as a primary treatment strategy for patients with
paroxysmal AF. Although a significant number of studies have evaluated the
potential benefits of catheter ablation compared with anti-arrhythmic drug (AAD)
therapy, to date, there are only a small number of randomised controlled trials
in the literature, and several issues remain unsolved. The aim of this review is
to analyze the current literature regarding this important issue and further
discuss the question, whether catheter ablation may be more beneficial when
compared to AAD therapy.
PMID- 28496860
TI - Left Atrial Appendage Thrombus Despite Anticoagulation.
AB - The American College of Cardiology Foundation/American Heart Association task
force on practice guidelines recommend therapeutic anticoagulation for at least 3
weeks prior to cardioversion in patients with atrial fibrillation of 48-hour
duration or longer, or when the duration of atrial fibrillation is unknown. This
case report demonstrates the presence of thrombi in the left atrial appendage
despite adequate anticoagulation, challenging the current guidelines. Therapeutic
anticoagulation for at least 3 weeks followed by transesophageal echocardiography
in search of thrombus may enhance thromboembolic safety of elective
cardioversion. Atrial fibrillation (AF) and heart failure (HF) have emerged as
major cardiovascular epidemics in developed nations over the past decade. They
share similar risk factors, seem to mutually accelerate progression and are
associated with increased morbidity and mortality. Their relationship involves
complex hemodynamic, neuro-hormonal, inflammatory and electrophysiologic
mechanisms, which go beyond just mutual risk factors. This review focuses on
updates in AF and HF with a hope of better understanding this relationship and
the management of this complex duo.
PMID- 28496859
TI - Anti-Arrhythmic Agents in the Treatment of Atrial Fibrillation.
AB - Although atrial fibrillation (AF) is the most common sustained arrhythmia seen
during daily cardiovascular physician practice, its management remained a
challenge for cardiology physician as there was no single anti-arrhythmic agents
proved to be effective in converting atrial fibrillation and kept its
effectiveness in maintaining sinus rhythm over long term. Moreover all the anti
arrhythmic agents that are used in treatment of AF were potentially pro
arrhythmic especially in patients with coronary artery disease and structurally
abnormal heart. Some of these drugs also have serious non cardiac side effects
that limit its long term use in the management of atrial fibrillation. Several
new and investigational anti-arrhythmic agents are emerging but data supporting
their effectiveness and safety are still limited. In this systematic review we
examine the efficacy and safety of these medications supported by the major
published randomized trials, meta-analyses and review articles and conclude with
a summary of guidelines recommendations.
PMID- 28496861
TI - Cardiac Remodeling After Atrial Fibrillation Ablation.
AB - Radiofrequency catheter ablation procedures are considered a reasonable option
for patients with symptomatic, drug refractory atrial fibrillation (AF). Ablation
procedures have been reported to effectively restore sinus rhythm and provide
long-term relief of symptoms. Both electrical and structural remodeling occurs
with AF. A reversal of the electrical remodeling develops within 1 week after
restoration to sinus rhythm following the catheter ablation. The recovery rate is
faster in the right atrium than the left atrium. Reverse structural remodeling
takes longer and is still present 2 to 4 months after restoration of sinus
rhythm. The left atrial transport function also improves after successful
catheter ablation of AF. Left atrial strain surveys from echocardiography are
able to identify patients who respond to catheter ablation with significant
reverse remodeling after ablation. Pre-procedural delayed enhancement magnetic
resonance imaging is also able to determine the degree of atrial fibrosis and is
another tool to predict the reverse remodeling after ablation. The remodeling
process is complex if recurrence develops after ablation. Recent evidence shows
that a combined reverse electrical and structural remodeling occurs after
ablation of chronic AF when recurrence is paroxysmal AF. Progressive electrical
remodeling without any structural remodeling develops in those with recurrence
involving chronic AF. Whether progressive atrial remodeling is the cause or
consequence during the recurrence of AF remains obscure and requires further
study.
PMID- 28496862
TI - Cost-Effectiveness of Atrial Fibrillation Ablation.
AB - Atrial fibrillation (AF) is a frequently encountered rhythm disorder,
characterized by high recurrence rate, frequent hospitalizations, reduced quality
of-life and increased the risk of mortality, heart failure and stroke. Along with
these clinical complications this type of arrhythmia is the major driver of
health-related expenditures. Radiofrequency catheter ablation (RFA) of atrial
fibrillation has been shown to improve freedom from arrhythmia survival, reduce
re-hospitalization rate and provide better quality-of-life as compared with rate
control and rhythm control with antiarrhythmic therapy. Efficacy of AF ablation
in terms of outcomes and costs has an evolving importance. In this review, we
aimed to highlight current knowledge on AF ablation clinical outcomes based on
results of randomized clinical trials and community-based studies, and overview
how this improvement in clinical end-points affects costs for arrhythmia care and
cost-effectiveness of AF ablation.
PMID- 28496863
TI - Effect of Age on Outcomes of Catheter Ablation of Atrial Fibrillation.
AB - Age has a great impact in the development of atrial fibrillation, which is the
most common arrhythmia found in the elderly. The higher risk of stroke, heart
failure and mortality associated with atrial fibrillation highlights the need for
successful therapeutic interventions that can translate in better outcomes in
this population. The introduction of catheter ablation has revolutionized the
management of atrial fibrillation over the past decades with an undeniable impact
in morbidity, mortality and quality of life. This benefit has not been fully
extended to the older patients due to the lack of definitive data from randomized
control trials assessing the impact ofrhythm control strategies such as catheter
ablation in this population, in whom a rate-control strategy has been suggested
as a better therapeutic option. In this review, we summarize the pathogenesis of
atrial fibrillation in the elderly, the benefits and complications of catheter
ablation reported in the literature and the impact of age in the outcomes of
ablation compared to younger populations.
PMID- 28496865
TI - Building Atrial Fibrillation Awareness: Is it Time to get Beyond the Top Line?
AB - Public awareness of atrial fibrillation and its consequences is increasing. In
the current environment, this is driven largely by promotion of individual
therapies. This editorial discusses the need for greater depth in the discussion
of the disease state, its progression and economic consequences as well as the
risk of death and disability. The adverse effects of therapies on cardiovascular
outcomes is a major need in public education. New initiatives should address
these important new insights and needs.
PMID- 28496864
TI - Catheter Ablation of Atrial Fibrillation in Females.
AB - Catheter ablation for the management of atrial fibrillation (AF) has evolved as a
successful therapy widely used. Women with AF show a higher risk for AF-related
morbidity due to stroke, a poorer tolerance to antiarrhythmic pharmacological
therapy and a weaker quality of life; for this reason a curative, catheter-based
approach for AF appears very attractive in women. Reported details on female AF
population undergoing catheter ablation, as well as success and complication
rates will be reviewed.
PMID- 28496866
TI - Atrial Fibrillation after Radiofrequency Ablation of Type I Atrial Flutter.
AB - Typical atrial flutter (AFL) or type I AFL is the most common type of
macroreentrant atrial tachycardia. Its prevalence increases with age and is more
common in men. Ablation of the cavo-tricuspid isthmus (CTI), a critical part of
the circuit, is safe and highly effective. Despite the long-term efficacy of this
therapy, a significant proportion of patients undergoing CTI ablation will
develop atrial fibrillation (AF) during the follow-up and identifying them can
have an important impact on their management. PV isolation and typical flutter
ablation during the same procedure may be an effective treatment strategy for
patients with clinical documentation of both arrhythmias.
PMID- 28496868
TI - Automated Detection of Complex Fractionated Atrial Electrograms In Substrate
Based Atrial Fibrillation Ablation: Better Discrimination with a New Setting of
CARTO(r) Algorithm.
AB - Background and purpose: Up until recently complex fractionated atrial electrogram
(CFAE) ablation has been considered as time consuming and its achievement as
challenging, especially for non experimented operators. Moreover, results of
substrate ablation based on CFAE detection in atrial fibrillation (AF) are very
disparate, mainly because of the operator's subjective electrogram visual
analysis and the difficult distinction between CFAEs really involved in AF
perpetuation from other CFAE. Automatic detection provided by 3D mapping system
(CARTO(r) algorithm) can be helpful but is not selective enough, drawing too wide
CFAE areas. We sought to demonstrate a better selectivity of a new CFAE algorithm
setting in order to better discriminate CFAEs really involved in AF perpetuation
from other CFAE. Methods and subjects: A population of 32 patients (60.4+/-12.7
years) with paroxysmal (n=3) AF (PAF), persistent (n=16) AF (PeAF) or long
standing persistent (n=13) AF (LSPeAF), and AF history =56+/-65 months, underwent
CFAE ablation based on visual analysis. Before ablation, left atrium CFAE mapping
was performed on CARTO(r) shortest complex interval (SCI) algorithm and
reanalyzed after ablation with the two different settings: nominal (SCI 60
120ms/0.05-0.15mV) vs. customized setting (SCI 30-40ms/0,04-0.15mV). CFAE areas
automatically detected by both settings (CFAE-CARTO(r) areas) were respectively
measured. The decision to ablate CFAE was only based upon the operator's
electrogram visual analysis taken as reference because of high AF termination
rate (93.7%) due to operator's CFAE selection experience. These ablation points
drawn reference-CFAE areas involved in AF perpetuation (ablation point=60mm2)
allowing to compare the selectivity of the two previous automatic maps. Results:
With the customized CARTO(r) SCI setting, we observed a significant reduction of
CFAE areas detected by CARTO(r) (CFAE-CARTO(r) areas) and of the ablated CFAE
surface inside non-CFAE CARTO(r) areas, (30.6+/-20.5cm2 vs. 68.8+/-24.5cm2,
p<0.0001, and 1.86+/-1.82% vs. 3+/-3%, p=0.003). Furthermore the proportion of
ablated areas/detected CFAE-CARTO(r) areas were higher with customized setting
(38.2+/-19.6% vs. 20.4+/-17.5%, p=0.008). Conclusions: This new customized CFAE
algorithm setting is significantly more selective than the nominal one and allows
an automated detection of CFAE really involved in AF perpetuation truer to an
efficient experienced operator's electrogram visual analysis.
PMID- 28496867
TI - Atrial Fibrillation - A Common Ground for Neurology and Cardiology.
AB - Atrial fibrillation (AF) has a huge impact on clinical stroke because it is the
primary cause of cardio-embolism, which constitutes ~20% of all strokes. As a
result, there is a great need to explore safer and more effective primary and
secondary prophylactic agents. In this article, we discuss the overlapping issues
pertaining to AF from both a neurology and cardiology standpoint. We focus on the
dynamic interplay of neurovascular and cardiovascular diseases in relation to AF,
traditional and novel risk factors for AF leading to stroke, impact of AF on
cognitive decline, and current upstream medical and surgical options for embolism
prophylaxis.
PMID- 28496870
TI - Differences In Tissue Injury and Ablation Outcomes In Atrial Fibrillation
Patients - Manual versus Robotic Catheters.
AB - Robots have gained their place in almost all areas of our daily life. Robotic
systems have been introduced for ablation therapies associated with the hope of
automation of procedures, increase in precision of lesion placement, improved
energy transmission to the tissue and reduction in radiation exposure of the
patients and the interventionalist. Finally, they may be associated with higher
comfort for the operator by transferring his work into the control room and
thereby supersede wearing sterile and radiation protective clothing. Systems
providing a remote mechanical replacement of the operators' hands have been
introduced as well as systems guiding the catheter tip by external magnets.
Guiding of the catheter tip has major impact on contact to the tissue and thereby
modifies energy transmission. This may be advantageous in terms of higher
catheter stability and modification of contact towards a more constant than
intermittent type of contact. However, increasing contact bears the risk of
mechanical perforation and excessive energy delivery. Many clinical studies have
been conducted evaluating novel remotely guiding techniques in atrial
fibrillation ablation procedures. Although only a few of them are prospectively
randomized, reduction in fluoroscopy exposure has been found in most of the
trials. Data on outcome is less uniform. It seems that remote navigation does not
improve outcomes and on the other hand does not increase complication rates.
However, large prospectively randomized trials conducted by operators well
skilled not only in manual but also in remote techniques would be needed to
compare outcomes particularly in terms of decrease in complication rates.
Finally, the type of navigation chosen actually is and probably will remain a
question of personal preference.
PMID- 28496869
TI - Treatment Considerations for a Dual Epidemic of Atrial Fibrillation and Heart
Failure.
AB - Atrial fibrillation (AF) and heart failure (HF) have emerged as major
cardiovascular epidemics in developed nations over the past decade. They share
similar risk factors, seem to mutually accelerate progression and are associated
with increased morbidity and mortality. Their relationship involves complex
hemodynamic, neuro-hormonal, inflammatory and electrophysiologic mechanisms,
which go beyond just mutual risk factors. This review focuses on updates in AF
and HF with a hope of better understanding this relationship and the management
of this complex duo.
PMID- 28496871
TI - Silent Cerebral Embolism during Atrial Fibrillation Ablation:Pathophysiology,
Prevention and Management.
AB - Although many efforts have been directed to improve atrial fibrillation
transcatheter ablation safety, thromboembolism to the brain remains one of the
major complications. In fact several studies have confirmed occurrence of silent
cerebral embolic lesions by post-procedure magnetic resonance imaging. The
present review will focus on the possible mechanisms leading to silent cerebral
embolism in an attempt to provide recommendations holding the potential to reduce
the incidence of this clinically relevant complication.
PMID- 28496872
TI - Atrial Fibrillation and Renal Disease.
AB - Co-incidence of atrial fibrillation and renal dysfunction in general population
is described in many epidemiological studies. Major issue is optimal
anticoagulation in patients with atrial fibrillation and renal disease warranting
balance between risks of ischemic stroke and hemorrhages. The second issue is
catheter ablation of AF patients with renal dysfunction. Both issues are
discussed in this paper.
PMID- 28496873
TI - Connexin Remodeling Contributes to Atrial Fibrillation.
AB - Atrial fibrillation significantly contributes to mortality and morbidity through
increased risk of stroke, heart failure and myocardial infarction. Investigations
of mechanisms responsible for the development and maintenance of atrial
fibrillation have highlighted the importance of gap junctional remodeling.
Connexins 40 and 43, the major atrial gap junctional proteins, undergo
considerable alterations in expression and localization in atrial fibrillation,
creating an environment conducive to sustained reentry. Atrial fibrillation is
initiated and/or maintained in this reentrant substrate. This review will focus
on connexin remodeling in the context of underlying mechanism and possible
therapeutic target for atrial fibrillation.
PMID- 28496874
TI - The Progressive Nature of Atrial Fibrillation:A Rationale for Early Restoration
and Maintenance of Sinus Rhythm.
AB - Atrial fibrillation (AF) is the manifest outcome of a multifactorial, progressive
disease process,secondarily or primarily involving the atrial chambers. The
slowly progressive electrostructural alterations diffusely involve the atrial
substrate and lead to persistent and permanent forms of AF. Although the
progression of the AF disease process is variable and associated with the
development of comorbid conditions, rhythm restoration therapies, particularly
catheter ablation,provide higher acute and long-term success rates in paroxysmal
than non-paroxysmal AF. This review of literature aims to discuss how early
restoration and maintenance of sinus rhythm especially using novel approaches can
influence the progressive nature of atrial fibrillation.
PMID- 28496875
TI - Hybrid Therapy for Atrial Fibrillation - Optimizing Treatment Strategies.
AB - Endocardial atrial fibrillation (AF) ablation techniques enable one to
characterize the underlying substrate in order to tailor the ablation procedure
but these ablation lesions are not always transmural nor long lasting. Surgical
AF ablation techniques, on the other hand, create reliable linear lesions but the
lesion set is based on empirical assumptions rather than specific patient
characteristics. Performed in combination, both approaches seem to be
complementary as they overcome their mutual shortcomings. Several hybrid or
convergent ablation strategies with the use of various energy sources have been
described. Medium and long term results are encouraging, especially in
challenging settings such as persistent AF and failed endocardial catheter
ablations.
PMID- 28496876
TI - Diabetes, Obesity and Atrial Fibrillation: Epidemiology, Mechanisms and
Interventions.
AB - Body mass index (BMI) is a powerful predictor of death, type 2 diabetes (T2DM)
and cardiovascular (CV) morbidity and mortality. Over the last few decades, we
have witnessed a global rise in adult obesity of epidemic proportions. Similarly,
there has been a parallel increase in the incidence of atrial fibrillation (AF),
itself a significant cause of cardiovascular morbidity and mortality. This may be
partly attributable to advances in the treatment of coronary heart disease (CHD)
and heart failure (HF) improving life expectancy, however, epidemiological
studies have demonstrated an independent association between obesity, diabetes
and AF, suggesting possible common pathophysiological mechanisms and risk
factors. Indeed, cardiac remodeling, haemodynamic alterations, autonomic
dysfunction, and diastolic dysfunction have been reported in obese and diabetic
cohorts. Moreover, diabetic cardiomyopathy is characterized by an adverse
structural and functional cardiac phenotype, which may predispose to the
development of AF. In this review, we discuss the pathophysiological and
mechanistic relationships between obesity, diabetes and AF, and some of the
challenges posed in the management of this high-risk group of individuals.
PMID- 28496878
TI - High Incidence of Atrial Fibrillation or Flutter in Stroke Patients Who Have the
Clinical Risk Factors for Stroke.
AB - The incidence of stroke in patients with atrial fibrillation or flutter (AF) is
well known and depends on the presence of risk factors. The incidence of AF in
patients who have a stroke and its relationship to risk factors is not as clear,
however, because many stroke patients may have occult intermittent AF that is not
present at the time of stroke and is not diagnosed. To better assess the
incidence of AF, we studied the clinical records and all the 12 lead ECGs in a 14
year medical center data base of 985 patients admitted with ischemic stroke over
a 3 year period and correlated the incidence of AF with the presence of the
stroke risk factors. Of the stroke patients with congestive heart failure 61.9%
had AF (95%CL 54.4, 68.9), with age >/=75 years 45.2% had AF(CL 41.0,49.4), with
coronary artery disease 42.9% had AF (CL 36.8,49.2), with diabetes 39.2% had AF
(CL 32.8,46.1) and with hypertension 33.7 % had AF(CL 30.5,37.1) , all
significantly higher than without these risk factors. Patients with > 1 risk
factor or with echo abnormalities, especially left atrial enlargement, had an
even higher incidence of AF. These findings suggest that AF may be a very common
mechanism whereby the stroke risk factors cause stroke. Stroke patients in normal
sinus rhythm with these risk factors should be monitored for AF so they can
receive anticoagulation to prevent a subsequent stroke if AF is diagnosed.
PMID- 28496877
TI - Homogenization of Atrial Electrical Activities: Conceptual Restoration of
Regional Electrophysiological Parameters to Deter Ischemia-Dependent
Conflictogenic Atrial Fibrillation.
AB - Atrial fibrillation (AF) as a severe arrhythmia is now spreading worldwide at
overwhelmingly high rates, particularly in elderly patients. Despite new
insights, the mechanisms underlying AF are not conclusively determined yet.
Taking into account the ischemic origin of arrhythmia induction (according to the
so-called conflictogenic atrial fibrillation, declared recently) restoration of
regional electrophysiological parameters is essential in tackling AF. We
hypothesized that some atrial electrophysiological parameters, preferably the
effective refractory period, might need to be controlled to prevent AF. All the
remaining parameters - conduction velocity, conduction time, recovery time,
vulnerability, excitability, repolarization etc. being as if secondary and less
important could be ignored. Homogenization of the milieu producing AF might be
implemented, at least theoretically, through restoration of blood supply in
ischemic areas and/or via attenuation of electrophysiological differences between
conflicting regions by delivery of atrial sub-threshold non-captured pulse
trains. Adjunctive therapy by drugs containing vasodilatory features and
affecting the effective refractory period appears to be fundamental. Thus,
stabilization of disorganized atrial cellular activities likely may lead to the
recovery of atrial excitable characteristics. Despite the lack of compelling
evidence, the application of the concept may be helpful in order to search for
more precise and more effective methods to favorably change the refractory
period. Further studies are necessary to determine whether restoration or
improvement of blood circulation of atrial wall is feasible. Based on such
considerations a novel preventive AF strategies are to be designed.
PMID- 28496879
TI - The Role of the Atrial Neural Network In Atrial Fibrillation: The Metastatic
Progression Hypothesis.
AB - With the advent of catheter ablation of atrial fibrillation (AF) there has been
acceleration in our understanding of the mechanisms underlying the etiology of
this common clinical arrhythmia. In this regard, the role of the intrinsic
cardiac autonomic nervous system in the initiation and maintenance of AF began to
receive attention in numerous experimental and clinical investigations. Up to
now, the focus has been on the large ganglionated plexi (GP) which are located in
the posterior left atrium mainly at the pulmonary vein-atrial junctions. As long
term outcomes have been reported and single procedures have indicated diminished
success rates particularly for persistent/long standing persistent AF, emphasis
has begun to shift away from the pulmonary vein isolation (PVI) alone as well as
GP ablation with or without PVI. An understanding of the atrial substrate
represented by the extensions of the intrinsic cardiac autonomic system
constituting the atrial neural network is beginning to evolve. In this review,
the contribution of the intrinsic cardiac autonomic nervous system to the
etiology of AF is addressed, particularly in regard to the greater prevalence of
AF in the elderly. In addition, we emphasize the involvement of the atrial neural
network in the "metastatic" progression of paroxysmal to persistent and long
standing persistent forms of AF.
PMID- 28496880
TI - Left Atrial Thrombosis Despite Dabigatran Therapy.
AB - Dabigatran is a novel anticoagulation which has been approved as an alternative
to warfarin therapy for non-valvular atrial fibrillation. Use of Dabigatran for
approved indications as well as off label use has dramatically increased after
Federal Drug Administration (FDA) approval. Our patient had left atrial
thrombosis even after being on Dabigatran for more than one month which raises
question about safety and efficacy of use of dabigatran around cardioversion and
ablation.
PMID- 28496881
TI - Hiatal Hernia Is Associated With an Increased Prevalence of Atrial Fibrillation
in Young Patients.
AB - Purpose: Hiatal hernia (HH) causes protrusion of the stomach into the chest
cavity, directly impinging on the left atrium and possibly increasing
predisposition to atrial arrhythmogenesis. However, such association has not been
fully explored. The objective was to determine if an association between HH and
atrial fibrillation (AF) exists and whether there are age- and sex-related
differences. Methods: Adult patients diagnosed with HH from 1976 to 2006 at Mayo
Clinic Rochester, Minnesota, were evaluated for AF. The number of patients with
AF and HH was compared to age- and sex-matched patients with AF reported in the
general population. Long-term outcomes were compared to corresponding county and
state populations. Results: During the 30-year period, 111,429 patients were
diagnosed with HH (mean age 61.4 +/- 13.8 years, 47.9% male) and 7,865 patients
(7.1%) also had a diagnosis of AF (mean age 73.1 +/- 10.5 years; 55% male). In
younger patients (<55 years), the occurrence of AF was 17.5-fold higher in men
with HH and 19-fold higher in women with HH compared to the frequency of AF
reported in the general population. Incidence of heart failure for patients with
AF and HH was worse compared to the overall county population, but better than
for those with AF. Similarly, mortality was worse in patients with AF and HH
compared to the overall state population, but better than for those with AF in
the county. Conclusion: Hiatal hernia appears to be associated with increased
frequency of AF in both men and women of all age groups, but particularly in
young patients. Further studies are needed to investigate this possible
association and underlying mechanism.
PMID- 28496882
TI - Conversion of Recent-Onset Atrial Fibrillation: Which Drug is the Best?
AB - Introduction: Vernakalant is a new, safe and effective drug used intravenously.
It has proven to be more rapid in converting recent onset atrial fibrillation
(AF) to sinus rhythm compared to placebo, amiodarone, propafenone and flecainide
in clinical studies with few patients. At present no study has been conducted
comparing these three drugs with a more substantial number of patients. The aim
of our study is to compare the time to conversion to sinus rhythm, hospital stay
and adverse events between vernakalant versus flecainide and propafenone in
patients with a recent-onset AF. Materials and Methods: 150 hemodynamically
stable patients with recent onset AF without structural heart disease were
prospectively included. A single oral dose of propafenone 600 mg was administered
to 50 patients; 50 patients received intravenous vernakalant; and 50 patients
received a single oral dose of flecainide 300 mg. Clinical and laboratory
variables were recorded. Results: Baseline characteristics were similar in the
three groups.Time to conversion to sinus rhythm was 12 minutes in the vernakalant
group versus 151 minutes in the propafenone group and 162 minutes in flecainide
group (p< 0.01) The hospital stay was 243 minutes in the vernakalant group versus
422 minutes in the propafenone group and 410 minutes in flecainide group (p<0.01)
(Figure 2). No adverse events were reported. Conclusion: The time to conversion
to sinus rhythm and hospital stay were statistically shorter in vernakalant group
compared to flecainide and to propafenone. There were no adverse events in the
three groups.
PMID- 28496883
TI - Atrial Electrical Remodeling and Sleep Disordered Breathing.
PMID- 28496884
TI - Left Atrial Thrombus Despite Anticoagulation: The Importance Of Homocysteine.
AB - Patients in atrial fibrillation may have left atrial thrombi or strokes despite
adequate anticoagulation. It is important to consider elevated plasma total
homocysteine (tHcy) as a treatable clotting factor that may explain such cases.
Metabolic B12 deficiency is common even in patients with a "normal" serum B12.
Measurement of holotranscobalamin, methylmalonic acid or, in folate-replete
patients, tHcy are necessary to diagnose metabolic B12 deficiency when the serum
B12 is below 400 pmol/L. Elevated tHcy quadruples the risk of stroke in atrial
fibrillation, and is far more common than the usual clotting factors for which
testing is commonly performed: among patients attending.
PMID- 28496885
TI - World Atrial Fibrillation Awareness Day - Time to Spread the Message.
PMID- 28496886
TI - Highlights from the 5th Kansas City Heart Rhythm Symposium.
PMID- 28496887
TI - Functional Pulmonary Vein Isolation During Atrial Fibrillation Ablation.
AB - We report a case of apparent isolation of the right inferior pulmonary vein
during atrial fibrillation ablation coincident with the onset of an atrial
tachycardia. This report highlights the importance of assessing pulmonary vein
conduction during sinus or paced rhythm at relatively long cycle length, rather
than in atrial fibrillation or atrial tachycardia.
PMID- 28496888
TI - Atrio-Esophageal Fistula After AF Ablation: Pathophysiology, Prevention
&Treatment.
AB - Atrioesophageal fistula is an extremely rare but often fatal late complication of
atrial fibrillation ablation procedures resulting from massive thermal injury to
the esophagus and surrounding structures. Causes of death include cerebral air
embolism, massive gastrointestinal bleeding, and septic shock. Because of its
exceptionally low rate of occurrence, no predictors of lesion development have
been found and there has not been an uniform approach to either early diagnosis
or corrective therapy. Currently, preventive strategies include empirically
reducing power titration during PVI and/or while ablating the posterior left
atrial wall, limiting energy delivery time and number, avoiding overlapping
ablation lines as well as monitoring intraluminal esophageal temperature. In
addition, it has been suggested to use conscious sedation rather than general
anesthesia for better pain perception, monitoring intraprocedural esophageal
position in relation to the posterior left atrium and extensive patient education
regarding signs and symptoms of esophageal injury. Early diagnosis is essential
to enable an aggressive treatment including stenting and/or surgical intervention
to minimize the excessive morbidity and mortality associated with this condition.
Unfortunately, despite application of such preventive measures, cases of complete
atrial-esophageal fistula have still been reported.
PMID- 28496889
TI - The Challenge of Chamber Stiffness Determination in Chronic Atrial Fibrillation
vs. Normal Sinus Rhythm: Echocardiographic Prediction with Simultaneous
Hemodynamic Validation.
AB - Echocardiographic diastolic function (DF) assessment remains a challenge in
atrial fibrillation (AF), because indexes such as E/A cannot be used and because
chronic, rate controlled AF causes chamber remodeling. To determine if
echocardiography can accurately characterize diastolic chamber properties we
compared 15 chronic AF subjects to 15, age matched normal sinus rhythm (NSR)
subjects using simultaneous echocardiography-cardiac catheterization (391 beats
analyzed). Conventional DF parameters (DT, Epeak, AT, Edur, E-VTI, E/E') and
validated, E-wave derived, kinematic modeling based chamber stiffness parameter
(k), were compared. For validation, chamber stiffness (dP/dV) was independently
determined from simultaneous, multi-beat P-V loop data. Results show that neither
AT, Epeak nor E-VTI differentiated between groups. Although DT, Edur and E/E' did
differentiate between groups (DTNSR vs. DTAF p < 0.001, EdurNSR vs. EdurAF p <
0.001, E/E'NSR vs. E/E'AF p < 0.05), the model derived chamber stiffness
parameter k was the only parameter specific for chamber stiffness, (kNSR vs. kAF
p <0.005). The invasive gold standard determined end-diastolic stiffness in NSR
was indistinguishable from end-diastolic (i.e. diastatic) stiffness in AF (p =
0.84). Importantly, the analysis provided mechanistic insight by showing that
diastatic stiffness in AF was significantly greater than diastatic stiffness in
NSR (p < 0.05). We conclude that passive (diastatic) chamber stiffness is
increased in normal LVEF chronic, rate controlled AF hearts relative to normal
LVEF NSR controls and that in addition to DT, the E-wave derived, chamber
stiffness specific index k, differentiates between AF vs. NSR groups, even when
invasively determined end-diastolic chamber stiffness fails to do so.
PMID- 28496890
TI - Performance of the Cockcroft-Gault, MDRD and CKD-EPI Formulae in Non-Valvular
Atrial Fibrillation: Which one Should be Used for Risk Stratification?
AB - Background: Renal dysfunction is a strong predictor of adverse events in patients
with atrial fibrillation (AF). The Cokcroft-Gault, Modification of Diet in Renal
Disease (MDRD) and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI)
equations are available for estimating the glomerular filtration rate (GFR). No
comparisons between these equations have yet been performed in patients with non
valvular AF concerning their mid-term prognostic performance. Methods: Cross
sectional study of 555 consecutive patients with non-valvular AF undergoing
transesophageal echocardiogram. We tested the prognostic performance of the
aforementioned GFR estimation formulae, namely their ability to predict all-cause
mortality (primary endpoint) and major cardiac adverse or ischemic
cerebrovascular events (secondary endpoints) during an average follow-up of 24
months. Results: Regarding the primary endpoint, Cockcroft-Gault (AUC=0.749+/
0.028) was superior to both MDRD (AUC=0.624+/-0.039) and CKD-EPI (AUC=0.641+/
0.034) [p<0.001 both comparisons] while CKD-EPI was superior to MDRD (p=0.011).
Cockcroft-Gault was marginally superior to both MDRD (AUC=0.673+/-0.049 vs.
AUC=0.586+/-0.054, p=0.041) and CKD-EPI (AUC=0.673+/-0.049 vs. AUC=0.604+/-0.054,
p=0.063) in the prediction of ischemic cerebrovascular events, while no
difference was found between CKD-EPI and MDRD. Concerning AUC for prediction of
MACE, Cockcroft-Gault was superior to MDRD (p=0.009) and CKD-EPI (p=0.012), while
CKD-EPI was similar to MDRD (p=0.215). Multivariate predictive models
consistently included Cockcroft-Gault formula along with CHADS2, excluding the
other two equations. Measures of reclassification revealed a significant
improvement in risk stratification for all studied endpoints with Cockcroft-Gault
instead of CKD-EPI. Conclusions: In patients with non-valvular AF, the Cockcroft
Gault more appropriately classified individuals with respect to risk of all-cause
mortality, ischaemic cerebrovascular event and major adverse cardiac event.
PMID- 28496891
TI - Renin Angiotenin Blocker Pre-treatment and Recurrence After Pulmonary Vein
Isolation in Patients with Paroxysmal and Persistent Atrial Fibrillation.
AB - Introduction: Pulmonary venous isolation has emerged as an effective method for
preventing atrial fibrillation (AF) recurrence. Yet, recurrence is common.
Angiotensin-receptor-blockers (ARBs) and angiotensin-converting-enzyme-inhibitors
(ACEI) are effective in reducing the extent of myocardial remodeling and
fibrosis. Our aim was to study whether pretreatment with ARBs and ACEI was
effective in decreasing recurrence after pulmonary vein isolation for patients
with AF. Methods: Three hundred and twelve consecutive patients who underwent
ablation from 12/2006 until 7/2010 were followed for at least one year. All
patients underwent MRI before ablation to assess atrial fibrosis. Data include
demographic characteristics, comorbidities, AF type and information regarding
treatment with ACEI or ARBs. Results: Most patients were men (62%), mean age was
64. Hypertension (HTN) was present in 60%. Their mean ejection fraction was 60%.
There were 104 patients (33.3%) treated with ACEI, and 13.5 % were treated with
ARBs prior to ablation. Ninety seven patients (31.1%) had AF recurrence. AF type
was a significant predictor for recurrence (recurrence with paroxysmal,
persistent and long-standing persistent: 23.75, 37.3 and 60%, respectively,
p=0.005). The most important factor predicting recurrence was increased pre
ablation atrial fibrosis (p<0.0001). Recurrence was more frequent in patients
treated with ACEI (40.4% vs 26.4% untreated patients, p=0.012). In the ARB
treated group, 38.1% vs 30.0% untreated experienced recurrence (p=0.3). After
multivariable adjustment for demographics, risk factors and atrial fibrosis,
treatment with ACEI was associated with increased rate of recurrence in patients
with persistent AF (hazard ratio: 2.6, p=0.003). There was no significant
relation between ACEI pretreatment and recurrence in patients with paroxysmal AF
(HR- 0.83, p=0.7), or between ARB pre-treatment and recurrence in patients with
paroxysmal as well as persistent AF (p=0.2 and 0.53, respectively). Conclusions:
Pretreatment with ACEI or ARBs is not associated with reduced recurrence rate in
patients with paroxysmal or persistent AF undergoing ablation.
PMID- 28496892
TI - Electrophysiological Evaluation of Thoracoscopic Pulmonary Vein Isolation.
AB - Although the majority of patients with atrial fibrillation and an indication for
non-pharmacological therapy is treated with catheter ablation, thoracoscopic
surgery is an emerging technique that aims at combining the results of the
classic Cox Maze operation with a less invasive approach. Recurrences after
thoracoscopic surgery have been mainly ascribed to incomplete ablation lines, but
literature on electrophysiological confirmation of thoracoscopic pulmonary vein
isolation is limited. Currently, surgical confirmation of uni- or bidirectional
conduction block may be hampered by insufficient resolution of the mapping
material available. Additionally uncertainty remains on the precise lesions sets
required, and how to tailor them to individual patients. In hybrid procedures,
electrophysiologists and surgeons join forces to combine their expertise and
skills which may lead to increased procedural success rates by minimizing the
chance of incomplete PV isolation or absence of conduction block across an
alternative ablation line. Here we describe techniques for thoracoscopic mapping
and present a literature review.
PMID- 28496893
TI - Catheter Ablation Targeting Complex Fractionated Atrial Electrogram in Atrial
Fibrillation.
AB - The relatively low success rates seen with pulmonary vein ablation in non
paroxysmal atrial fibrillation (AF) patients as compared to those with the
paroxysmal form of the arrhythmia have prompted electrophysiologists to search
for newer ablative strategies. A decade has passed since the initial description
of complex fractionated atrial electrogram (CFAE) ablation aimed at targeting the
electrophysiological substrate in atrial fibrillation. Despite intensive
research, superiority of CFAE-based ablation over other contemporary approaches
could not be demonstrated. Nevertheless, the technique has an adjunctive role to
pulmonary vein ablation in non-paroxysmal AF patients. Perhaps our incomplete
understanding of the complex AF pathophysiology and inadequate characterization
or determination of CFAE has limited our success so far. This review aims to
highlight the current challenges and future role of CFAE ablation. .
PMID- 28496894
TI - Atrial Fibrillation and Stroke Risk After Coronary Artery Bypass Grafting
Surgery.
AB - Background: The present multicentre study was aimed at determining the effect of
preoperative atrial fibrillation (preop-AF) as stroke risk factor in coronary
artery bypass graft surgery (CABG) during the perioperative period. Methods:
Patients undergoing isolated CABG surgery were enrolled from 21 Spanish centers.
Baseline variables related with perioperative stroke risk were recorded and
analysed. The Northern New England Cardiovascular Disease Study Group (NNECVDSG)
stroke risk schema was used to stratify stroke risk and compare predicted vs
observed neurologic outcomes in this study. Results: 26347 patients were enrolled
in the study. Prevalence of preop-AF was 4.2%, and was associated significantly
with major cardiovascular comorbidities. The stroke rate was 1.38% (365 strokes),
and it was slightly higher for patients with preop-AF vs non preop-AF, 1.82% vs
1.36%, p = 0.2. NNECVDSG schema showed good predictive ability calculating the
area under the receiver operating characteristic curve (c-statistic 0.696; 95% CI
0.668 to 0.723). To investigate the associations of baseline preoperative
variables with perioperative CABG-stroke a logistic regression model was
performed. Preop-AF impact on perioperative stroke was lower that other
variables. Preop-AF did not show an adverse impact in the quartiles groups
according to NNECVDSG Stroke Risk Index. Conclusion: Risk of perioperative stroke
in isolated CABG surgery patients is not significantly increased by preop-AF.
PMID- 28496895
TI - Safety and Efficacy of Atrial Fibrillation Ablation in Young Patients.
AB - Background: Outcome of catheter ablation of atrial fibrillation (AF) in young
patients has not been widely reported. This study describes the safety and
efficacy of radiofrequency catheter ablation (RFA) for atrial fibrillation in
patients forty years or younger. Methods and Results: Forty consecutive patients
who underwent fifty-two RFA procedures for symptomatic, drug-refractory
paroxysmal or non-paroxysmal AF were included in the study. The mean (SD) age of
the patients at time of initial procedure was 34.1 (5.6) years. Twenty-five
(62.5%) patients had paroxysmal AF, 6 (15%) patients had persistent AF, and 9
(22.5%) patients had longstanding persistent AF. Procedural safety and efficacy
were assessed based on patient status > 1 year after initial ablation procedure.
After a mean (SD) follow-up of 3.8 (2.9) years, 25 (62.5%) patients were free of
AF without antiarrhythmic drugs (AAD) and 40 (100%) patients experienced > 95%
reduction of AF burden on or off AADs. No major complications or adverse events
occurred during the study. Conclusions: Catheter ablation of AF is a favorable
therapeutic option for patients 40 years or younger, resulting in high rates of
procedural success with a low risk of major complications.
PMID- 28496896
TI - Left Atrial Appendage Occlusion for Stroke Prevention in Patients with
Nonrheumatic Atrial Fibrillation.
AB - Introduction: Atrial fibrillation is a common rhythm disorder, which is related
to a higher risk of thrombembolism resulting in a high rate of cerebral stroke or
transient ischemic attacks. According to the CHADS2- or CHA2DS2Vasc-Score there
is an indication for oral anticoagulation to prevent patients from mostly
disabling strokes. However, more than 50% of patients are not adequately treated
with oral anticoagulation due to different reasons, especially contraindications.
More than 90% of thrombi develop in the left atrial appendage (LAA), which lead
to the idea of developing devices to exclude the LAA from the systemic
circulation to prevent patients from embolisations. Another approach is surgical
ligation or removal of the LAA during operation procedures. Content: Different
devices and their clinical data are discussed in this review. Available
literature for most of the devices is evaluated and last but not least some
surgical results are discussed at the end. Existing data of randomized and non
randomized studies show that the concept of LAA-occlusion instead of
anticoagulation therapy works. However, complication rates during intervention
have to be kept in mind, but with adequate training also new and inexperienced
operators can do the procedure safely. Most data and the only randomized studies
are available for the Watchman Device. Despite some few complications like
pericardial effusions, bleeding complications and thrombus formation on the
devices, the data showed a non inferiority of device-implantation in comparison
with anticoagulation therapy in the first few years. In long term follow up more
than 4 years after implantation, there is even a superiority of the device
compared with anticoagulation therapy, safety issues are no longer significantly
different despite some periprocedural complications. This has to be reflected
with the background, that operators could treat 3 patients with a totally new
method, thereafter all patients had to be randomized into the study. So
experience was limited in the first phase of this trial. Surgical data vary much
due to different techniques of LAA-occlusion. With newer devices results are also
promising. Conclusion: LAA-occlusion is a developing field of interventional and
surgical techniques. The concept of LAA-occlusion could be proved in one
randomized trial. At least for patients contraindicated for anticoagulation
therapy, LAA-occlusion is a real alternative to only aspirin therapy or doing
nothing. With emerging techniques and lower complication rates, LAA-occlusion
might develop to a real alternative to anticoagulation therapy, at least for
vitamin-K-antagonists. There are no data available so far in comparison with new
oral anticoagulants. Further studies are needed to compare device therapy with
new oral anticoagulants.
PMID- 28496897
TI - Comparing Safety and Efficacy of Irrigated Radiofrequency Catheter Ablation
Versus Combined Cryoballoon and Catheter Ablation for Persistent Atrial
Fibrillation.
AB - Background: Catheter and cryoballoon ablation are established treatments for
atrial fibrillation. Frequently, substrate modification of the left atrium is
performed in patients with persistent AF or evidence of left atrial adverse
remodeling. We compared one year outcomes of AF ablation with substrate
modification utilizing radiofrequency catheter ablation (RFA) compared to a
combination of cryoballoon ablation with radiofrequency catheter ablation (HAFA).
Methods: Ablation for persistent AF was performed using stand-alone catheter
ablation (RFA group, n=31) or cryoballoon for pulmonary vein isolation with RFA
catheter ablation for substrate modification (HAFA group, n=21) and procedural
and clinical outcomes were analyzed. Pulmonary vein isolation and LA substrate
modification including creation of left atrial ablation lines and/or CFAEs was
performed in all patients. Patients were followed for up to one year. A three-
month blinding window was applied for analysis. Results: Clinical characteristics
were similar between groups. Total procedure (244.15+/-64.7 vs 235.5+/-54.6,
p=0.6) and fluoroscopy time (37+/-15.4 vs 29.5+/-15.7, p=0.96) were not different
between the HAFA and RFA groups, respectively. Periprocedural complications were
similar among groups. AF free survival was not significantly different between
Conclusions: Combined cryoballoon and catheter ablation for LA substrate
modification (HAFA) has similar safety and efficacy compared to stand-alone
catheter ablation for persistent AF. Recurrent atrial flutter is more frequently
observed after cryoballoon ablation for persistent AF.
PMID- 28496898
TI - Durable Pulmonary Vein Isolation: The Holy Grail of Atrial Fibrillation Ablation.
AB - The inability to achieve durable pulmonary vein isolation remains a major
limitation to catheter ablation for the treatment of atrial fibrillation (AF). In
this review, we discuss the research performed over the past decade investigating
methods to improve lesion permanence for the goal of durable pulmonary vein
isolation (PVI). Investigations evaluating procedural techniques, adjunctive
pharmacologic therapy, and newer energy sources designed to improve ablation
lesion permanence are discussed.
PMID- 28496899
TI - Role of Preprocedural Imaging in Catheter Ablation of Atrial Fibrillation.
AB - Catheter ablation is a well established and widely used therapy option of atrial
fibrillation. The use of 3D mapping systems to aid the ablation process has
become standard in most centers. Whether preprocedural imaging is an asset to
catheter ablation procedures is of debate. Available methods and the existing
evidence are outlined in this article.
PMID- 28496900
TI - Electrophysiological Evaluation of Pulmonary Vein Isolation.
AB - Since the pulmonary veins (PVs) were identified as a major source of AF triggers,
ablation strategies targeting the PVs have evolved from focal ablation inside the
PVs to wide area circumferential PV isolation (PVI) which at this juncture is the
standard approach. Despite the widespread popularity of PVI, a universal
definition is lacking. While "entrance block" is a generally accepted endpoint
for PVI, the role of "exit block" has yet to be determined. Inexcitability of the
circular ablation line has been introduced as a promising additional endpoint for
PVI and was associated with an improved clinical outcome in a randomized trial.
Correct interpretation of PV electrograms during an ablation procedure is
critical in terms of efficacy and safety. A variety of electrophysiological
techniques help to correctly differentiate components of complex PV electrograms.
Resumption of PV conduction after initially successful PVI leading to AF
recurrence remains a major problem and confirmation of bi-directional conduction
block does not exclude reversible tissue damage along the ablation line.
Prolongation of post-PVI monitoring and application of provocative procedures
such as the administration of adenosine after initial PVI to unmask dormant PV
conduction may improve clinical outcome although there is lack of valid data
supporting these strategies. This article aims on clarifying the
electrophysiological criteria for complete pulmonary vein isolation and the
explain the importance of this cornerstone in almost all atrial fibrillation
ablation procedures.
PMID- 28496901
TI - Role of Inflammation in Initiation and Perpetuation of Atrial Fibrillation: A
Systematic Review of the Published Data.
AB - Inflammation has emerged as being strongly associated with AF initiation and
perpetuation, including being implicated as a possible causal factor. Its role
needs further elucidation to assist with the optimal prevention and treatment of
AF using an individualized strategy. In the present review article the current
published data linking inflammation to AF is summarized.
PMID- 28496902
TI - Impaired Erythrocyte Deformability in Patients with Coronary Risk Factors:
Significance of Nonvalvular Atrial Fibrillation.
AB - Although coronary risk factors promote the formation of atherosclerotic plaque
containing activated platelets and inflammatory leukocytes, and play a pivotal
role in the development of coronary artery diseases (CAD), the hemorheological
effects of these risk factors on circulating intact erythrocytes, a major
component of whole blood cells, are poorly understood. Therefore, this study
aimed to quantify erythrocyte deformability in patients with coronary risk
factors, and enrolled 320 consecutive cardiac outpatients including 33 patients
with nonvalvular atrial fibrillation (AF). Patients with acute coronary syndrome
or valvular AF were excluded. Demographic variables obtained by medical records
were correlated with erythrocyte deformability investigated by our highly
sensitive and reproducible filtration technique. Among demographic variables,
triglyceride (p = 0.004), HbA1c (p = 0.014) and body weight (p = 0.020) showed
significant inverse correlation to the erythrocyte deformability. This
deformability was not associated with types of CAD (old myocardial infarction vs.
stable angina) or modality of treatment (percutaneous intervention vs. coronary
artery bypass grafting). Unexpectedly, stepwise multiple regression analysis
demonstrated that nonvalvular AF was the most significant contributor to the
impaired erythrocyte deformability (p = 0.002). Hypertension and dyslipidemia are
more prevalent in the AF patients (p < 0.001), and the erythrocyte deformability
was found to be impaired synergistically and significantly (p < 0.001) during the
stepwise accumulation of the coronary risk factors in addition to AF. In
conclusion coronary risk factors synergistically impair the erythrocyte
deformability, which may play an important role in critically stenotic coronary
arteries. Since the impairment of intact erythrocyte deformability is mostly
associated with nonvalvular AF, this common arrhythmia may reflect the coronary
risk accumulation.
PMID- 28496904
TI - Happy Holidays.
PMID- 28496903
TI - Exploring the Potential Role of Catheter Ablation in Patients with Asymptomatic
Atrial Fibrillation: Should We Move away from Symptom Relief?
AB - Although silent atrial fibrillation (AF) accounts for a significant proportion of
patients with AF, asymptomatic patients have been excluded from AF ablation
trials. This population presents unique challenges to disease management. Recent
evidence suggests that patients with asymptomatic AF may have a different risk
profile and even worse long-term outcomes compared to patients with symptomatic
AF. For the same reasons they might be more prone to side-effects of
antiarrhythmic drugs, including pro-arrhythmias. The poor correlation between
symptoms and AF demonstrated in several studies should caution physicians against
making clinical decisions depending on symptoms. Although current guidelines
recommend AF ablation only in patients with symptoms, more attention should be
paid to the AF burden and a rhythm control strategy has the potential to improve
morbidity and mortality in AF patients. However, limited data exist regarding the
use of catheter ablation for asymptomatic AF patients. As ablation techniques
have improved, AF ablation has become more widespread and complication rate
decreased. As a result, referrals of asymptomatic patients for catheter ablation
of AF are on the rise. In this review we discuss the many unresolved questions
concerning the role of the ablative approach in asymptomatic patients with AF.
PMID- 28496905
TI - Role of Bi-Atrial Pacing In Slowing The Progression of Paroxysmal Atrial
Fibrillation To Permanent Atrial Fibrillation.
AB - Introduction: Bi-atrial lead placement combined with atrial overdrive pacing has
demonstrated a reduction in percent time mode switched and mode switches per day.
This retrospective analysis compared long term outcomes of patients with right
atrial overdrive pacing alone (DAO) to patients having atrial overdrive with bi
atrial leads (BIA) in slowing the progression of paroxysmal atrial fibrillation
(PAF) to permanent continuous atrial fibrillation (CAF). Methods: Thirty-three
patients age 76.6 (+/-1.96) from our prior investigation were selected. The DAO
control group (N=16) had received a standard right atrial pacing lead. The BIA
group (N=17) had pacing leads placed in the right atrium and coronary sinus.
Patients were followed for a mean 1217 days (+/-838). Days of CAF was classified
as the date of final mode switch until analysis. Results: A total of 40,171
follow-up days were evaluated. The mean follow-up for both cohorts was 1217 days
(+/-838). The DAO group consisted of 15,318 days (mean 957 +/-761) and the BIA
group 24,853 days (mean 1461 +/-854). A lower total number of days were spent in
CAF in the BIA group versus the DAO group, 1380 vs 2197 respectively. Corrected
for follow-up duration, 5.55% days in CAF was seen in the BIA group vs. 14.34% in
the DAO group which did not reach statistical significance. Conclusions: Although
BIA overdrive pacing initially demonstrated reduced time in mode switch compared
to DAO alone, this analysis did not detect a reduction in progression to CAF.
More subjects or a longer follow up would be needed.
PMID- 28496906
TI - Risk of Cardiovascular Events, Stroke, Congestive Heart Failure, Interstitial
Lung Disease, and Acute Liver Injury: Dronedarone versus Amiodarone and Other
Antiarrhythmics.
AB - No published studies have evaluated the risks of cardiovascular (CV) events,
stroke, congestive heart failure (CHF), interstitial lung disease (ILD), and
severe acute liver injury (ALI) related to antiarrhythmics treatment in real
world clinical practice setting. We examined the relationship between the above
events and the selected antiarrhythmics in the real-world setting in the US.
Using a retrospective cohort design, the hazard ratios of the outcome events were
analyzed from 10,455 adult patients with a diagnosis of atrial
fibrillation/atrial flutter and a new treatment with dronedarone (comparison
drug), amiodarone, sotalol, flecainide, or propafenone between 07/20/2009 and
12/31/2010 from the Clinformatics Data MartTM database. The patients were
followed until: 1) switch to another antiarrhythmic drug, 2) occurrence of the
outcome event, 3) end of enrollment, or 4) end of the study period, whichever
occurred first. No significant differences were observed in the hazard ratios of
the outcome events between dronedarone, amiodarone, and the other
antiarrhythmics, except that amiodarone was associated with a higher risk of CV
events (adjusted HR = 1.7, 95%CI: 1.1-2.4) and stroke (adjusted HR = 2.0, 95%CI:
1.33.2), compared to dronedarone, especially amongst patients without a CHF
history (adjusted HR = 2.4, 95%CI: 1.4-3.8 and 2.2, 95%CI: 1.23.9). A higher risk
of CHF was also associated with amiodarone in patients without history of CHF at
baseline (adjusted HR = 2.7, 95%CI: 2.03.6). In this real-world investigation, no
difference in risk was observed between dronedarone, sotalol, and propafenone
initiators for CV events, stroke, CHF, ILD, and ALI. Amiodarone was associated
with higher risks of CV events, stroke, and CHF than dronedarone in patients
without a CHF history, indicating dronedarone could be an alternative therapy
option with lower risk of CV events than amiodarone for the above patients.
PMID- 28496907
TI - Mid-term Risk Stratification of Patients with a Myocardial Infarction and Atrial
Fibrillation: Beyond GRACE and CHADS.
AB - Background: We hypothesize that the discriminative performance of GRACE, ACHTUNG
Rule, CHADS2 or CHA2DS2-VASc may be lower in patients with a Myocardial
Infarction (MI) and concurrent atrial fibrillation (AF), as none of these scores
seem able to fully capture both atherothrombotic/thromboembolic risks. This study
aims to evaluate the mid-term prognostic performance of these algorithms in
patients with these two conditions and to analyze the utility of a score
combining GRACE and CHA2DS2-VASc. Methods: Observational retrospective single
centre cohort study including 1852 patients admitted with a MI. We tested the
prognostic performance of the aforementioned risk stratification schemes in
patients with vs. without AF at admission or during hospitalization. Primary
endpoints: a) total all-cause mortality, comprising intrahospital and post
discharge all-cause mortality; b) intrahospital all-cause mortality and c) all
cause mortality during follow-up. Furthermore, all three versions of the ACHTUNG
Rule were directly compared to their equivalent GRACE score versions, and a new
score, entitled GRACE-CHA2DS2-VASc, was developed and compared with GRACE.
Results: The mid-term prognostic performance of all scores was considerably lower
in patients with AF, corroborating our hypothesis. The ACHTUNG-Rule seemed
superior to GRACE in the prediction of post-discharge (AUC 0.790+/-0.032 vs.
0.685+/-0.038, p=0.079; integrated discrimination improvement index [IDI] of
0.166 and relative IDI of 83.7%) and total mortality (0.762+/-0.031 vs. 0.712+/
0.033, p=0.144; IDI of 0.042, relative IDI of 11.7%), but its performance
decreased in those with AF as well. GRACE-CHA2DS2-VASc was only marginally
superior to GRACE in discriminative performance, but detected truly low- (CHA2DS2
VASc <2; total mortality 0%) and high-risk patients (GRACE high-risk stratum, and
CHA2DS2-VASc >4; total mortality 44.3%) with considerable efficacy. Conclusions:
In patients with MI and concurrent AF, the GRACE, CHADS2 and CHA2DS2-VASc scores
seemed less accurate in the prediction of all-cause mortality. A hypothetic GRACE
CHA2DS2-VASc score or the recently developed ACHTUNG-Rule may eventually provide
a more rigorous approach to risk stratification in this high-risk setting.
PMID- 28496909
TI - Detection of Recurrent Atrial Fibrillation Utilizing Novel Technology.
AB - The true prevalence of AF is likely underestimated because episodes are often
sporadic and challenging to detect in a "real world" setting. This case report
will describe a 58-year-old atrial fibrillation patient with multiple cardiac
risk factors. After two ablations and one cardioversion, the patient failed to
remain in normal sinus rhythm. Shortly after AF returned, the decision was made
to perform a second cardioversion. Post-procedure, the patient was given a novel
FDA-approved, wireless ECG monitoring device compatible with the iPhone(r). This
device has the capability of recording and transmitting a single-channel ECG.
Within days, the patient began feeling symptomatic again and used his device to
transmit an ECG to his healthcare provider. Recurrent AF was detected and the
patient was directed to seek further evaluation. The success of this novel device
to detect recurrent AF highlights the "real world" applicability of using mHealth
technology more readily in patient care.
PMID- 28496908
TI - Advances in Left Atrial Appendage Occlusion Strategies.
AB - Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide and
associated with an elevated risk of thromboembolic stroke and systemic
embolization. The evidence suggests that ~90% of thrombi in patients with non
valvular AF are localized to the left atrial appendage (LAA). Therefore, it seems
reasonable to consider LAA exclusion in selected patients with AF for stroke
prevention. LAA exclusion can be achieved through a variety of surgical and
percutaneous techniques. Surgical methods include LAA amputation, ligation,
clipping and stapling. Whereas percutaneous strategies consist of endocardial
closure using an LAA occlusion device and epicardial LAA ligation using a snare
device. Even though several trials and registries of LAA exclusion have yielded
promising outcomes, at this time evidence for long term safety and efficacy seems
insufficient to recommend this approach to all patients with non-valvular AF.
Future prospective randomized trials are needed to assess the precise role for
these therapeutic options. Furthermore, there is a paucity of data on the
comparison of these strategies to the novel oral anticoagulants which also
deserves further attention. This review will carefully examine the current LAA
exclusion techniques and the available data.
PMID- 28496910
TI - Cardiac Arrest from Asystole During Endoscopic Retrograde
Cholangiopancreatography: A Rare But Fatal Complication.
AB - We present a rare complication of cardiac arrest from asystole in the setting of
prolonged endoscopic retrograde cholangiopancreatography(ERCP) procedure.
Cardiopulmonary complications of ERCP are rare but can be fatal. Therefore it is
essential to closely monitor the patient during ERCP. Immediate access to
resuscitation equipment facilitating prompt intervention in the unlikely event of
fatal cardiovascular collapse should be a part of standard ERCP protocol to
ensure life threatening complications are appropriately managed.
PMID- 28496911
TI - Anticoagulation and Clinical Outcomes in Heart Failure Patients With Atrial
Fibrillation: Findings From the ADHERE Registry.
AB - The risks and benefits of anticoagulation for patients with both heart failure
and atrial fibrillation are unclear. We hypothesized that anticoagulation was
associated with improved clinical outcomes of heart failure patients with atrial
fibrillation independent of other risk factors. We conducted a retrospective
cohort study of clinical registry data linked to Medicare claims for new users of
oral anticoagulation (warfarin) without contraindications, discharged home alive,
and stratified by CHADS2 score. Outcomes of interest were propensity score
adjusted estimates of the effects of warfarin at discharge on all-cause
mortality, thromboembolic events, major adverse cardiovascular events, and
bleeding events. Among 10,494 patients with heart failure and atrial
fibrillation, the 2249 patients newly treated with warfarin had lower 1-year
mortality (27.7% vs 39.3% for CHADS2 score <= 3 [P > .001]; 31.6% vs 41.8% for
CHADS2 score > 3 [P > .001]) than patients not treated with warfarin. There was
no significant difference in thromboembolic events, major adverse cardiovascular
events, or bleeding events at 1 year. After multivariate adjustment, exposed
individuals in both CHADS2 subgroups had lower adjusted 1-year mortality (CHADS2
<= 3: hazard ratio, 0.78 [95% confidence interval, 0.69-0.89]; CHADS2 >3: 0.78
[0.66-0.93]). In conclusion, warfarin use in heart failure patients with atrial
fibrillation was associated with improved survival at 1 year independent of
baseline CHADS2 score. However, there was no significant reduction in clinical
events, such as thromboembolic or major adverse cardiovascular events at 1 year
that might simply explain the survival benefit associated with warfarin.
PMID- 28496912
TI - Presence of A Left Atrial Appendage Thrombus After Successful Surgical Closure of
the Left Atrial Appendage: A Case Report.
AB - A 64-year-old African American woman presented for defibrillator threshold
testing (DFTs) after a recent hospitalization for ventricular fibrillation
terminated by her ICD. She had a known history of non-ischemic cardiomyopathy,
atrial fibrillation, rheumatic mitral valve disease s/p mitral valve replacement
and a redo after subsequent endocarditis. In preparation for the DFTs, the
patient underwent a transesophageal echocardiogram (TEE) to rule our left atrial
(LA) or LA appendage thrombus. Patient was found to have a surgically closed
appendage. Within the body of the closed appendage, a mobile thrombus was seen
with clot free areas surrounding the thrombus. Doppler and contrast studies
confirmed that there was no communication between the LA and the appendage. The
patient underwent DFTs without complication and a follow-up TEE confirmed the
presence of the clot in the non-communicating LA appendage.
PMID- 28496913
TI - Role of PR-Interval In Predicting the Occurrence of Atrial Fibrillation.
AB - The identification of individuals at high risk of developing atrial fibrillation
(AF) is important to prevent potentially lethal and invalidating complications of
this arrhythmia. Recently, several studies have investigated the association
between PR-interval and the risk of AF and have tested the value of PR-interval
in personalized risk scores for AF. However, the results of these studies are
generally conflicting. When looking for an association between a prolonged PR
interval (first-degree atrioventricular [AV] block vs. normal PR-interval) and an
increased risk of AF, not all studies were able to find a consistent and
statistically significant association. In two recent studies, however, the
investigators were able to show an increased risk of AF for individuals with PR
intervals in the short range compared with individuals in the middle range. The
existence of a true U-shaped relationship could potentially explain part of the
conflicting results from investigators only looking for an increased risk for
longer PR-intervals. However, regardless of these speculations, the association
seems relatively weak. The significance of PR-interval in risk prediction of AF
has been tested in three independent risk scores where model selection primarily
was based on improvement in c-statistics. In one risk score, PR-interval improved
the predictive value of the risk model, whereas it did not in the other two risk
scores. Further studies are warranted before any final conclusion can be drawn,
although based on the current evidence, it is reasonable to conclude that the
predictive value of PR-interval in AF risk prediction is limited.
PMID- 28496914
TI - Non-Fluoroscopic Transseptal Catheterization During Electrophysiology Procedures
using a Remote Magnetic Navigation System.
AB - Transseptal punctures are commonly performed, and left atrial (LA) access is
frequently lost during lengthy, complex electrophysiology (EP) procedures. We
describe a new technique for non-fluoroscopic re-crossing the fossa ovalis using
a new multielectrode transseptal sheath (TS) and a new remote magnetic catheter
navigation system (RMNS) (CGCI System, Magnetecs) that uses 8 rapid external
electromagnets for real-time navigation of a magnet-tipped electrode catheter
across the initial transseptal puncture site in 5 patients undergoing left-sided
ablation procedures. The three-dimensional (3D) position of a 8.5 Fr steerable TS
with 5-ring 5-15-15-5-mm spaced distal electrodes (Agilis ES(c), St Jude
Medical), and site of fossal ovalis crossing were "shadowed landmarks" on a 3D
electroanatomic mapping (EAM) system (EnSite/NavXTM, St Jude Medical). The TS
magnetic ablation catheter assembly was pulled-back to the inferior vena cava.
EAM landmarks were used with RMNS-guided "manual" and "automated" catheter
navigation modalities, until septal crossing was obtained. Transseptal re
crossing was successfully performed in all patients in 6.2+/-8.1 sec using the
"automated" RMNS-guided technique and in 30.4+/-28.4 sec using the "manual" RMNS
guided technique (p=0.01) without complications. This new RMNS was safely and
effectively used to perform non-fluoroscopic transseptal catheterization.
PMID- 28496916
TI - Cardioversion in Acute Atrial Fibrillation Without Anticoagulation.
AB - A major concern in cardioversion of newly detected atrial fibrillation is the
risk of thromboembolic events. The vast majority of these events occur in the
first week following cardioversion. Transesophageal echocardiography has
demonstrated that thrombus and dense spontaneous echo contrast may occur in the
left atrium and left atrial appendage in patients with acute atrial fibrillation
(<48 hours) scheduled for cardioversion. Moreover, atrial function may become
impaired immediately following successful cardioversion. The risk of
thromboembolic events increases with the presence of stroke risk factors, such as
heart failure, hypertension, diabetes, prior stroke, female sex and age above 65
75 years. Thus, the current guidelines of the ESC and ACC/AHA/Heart Rhythm
Society recommend that patients with acute atrial fibrillation should undergo
cardioversion under cover of unfractionated or low-molecular weight heparin
followed by oral anticoagulation for at least 4 weeks in patients in patients at
moderate-to-high risk for stroke. In line with the guidelines, new evidence from
a large patient population suggests that after successful cardioversion of acute
atrial fibrillation, patients have a low overall risk of thromboembolic events
without any anticoagulation when they have no risk factors for thromboembolism.
In contrast, the risk is in the range of 10% in patients with multiple classic
risk factors for thromboembolism.
PMID- 28496915
TI - Atrial Fibrillation and Stroke - Increasing Stroke Risk With Intervention.
AB - In this review, we focus on the important newly recognized appreciation for the
paradoxical increase in stroke and TIA as a result of intervention meant to treat
atrial fibrillation (AF) with the hope of decreasing stroke risk in the long
term. The impact of silent cerebral lesions recently appreciated as a potentially
major limitation and risk with AF ablation is explained. We categorize our
present understanding of how we can minimize risk and provide a platform for what
will undoubtedly be newer study, changes in the way procedures are done today,
and possibly vascular-based stroke-reduction strategies.
PMID- 28496917
TI - Utility of the Pulmonary Vein Ablation Catheter for Electrical Isolation of A
Left Sided Vena Cava Triggering Atrial Fibrillation.
AB - A persistent left sided vena cava (LSVC) can trigger atrial fibrillation. A 41
year old man with paroxysmal atrial fibrillation (PAF) and LSVC had all four
pulmonary veins and his LSVC electrically isolated from the left atrium with the
Pulmonary Vein Ablation Catheter (PVAC). At follow up patient described no
further episodes of AF. Single-shot ablation catheters such as the PVAC maybe
successfully and safely used for electrical isolation of a LSVC, though clearly
more experience is required to comprehensively evaluate this.
PMID- 28496918
TI - Cardiac Events Theoretically Cannot Be Produced By Non-Ischemic And/Or Iso
Ischemic Myocardium: Challenging Postulations And Vitality Of The Concept Of
"Ischemia-Dependent Conflictogenic Arrhythmias".
AB - Ischemia plays a key role in cardiac arrhythmogenesis, particularly in elderly
patients. Healthy, non-ischemic and structurally normal myocardium is universally
free from dysrhythmias. Thereby intact coronary blood flow prevents potential
cardiac events. Hypothetically, ischemia-related electrophysiological differences
are responsible for the supraventricular and/or ventricular rhythm
irregularities. The goal of this review is to determine the role of systemic and
coronary circulatory peculiarities and their association with heart rhythm
abnormalities. The current analytical review extends and enriches previous
knowledge about the influence of these peculiarities on the genesis of ischemia
dependent conflictogenic arrhythmias. Different intensity of coronary blood flow
resulting from stenotic obstacles or vasospasm potentially leads to the non
uniform perfusion of myocites thus creating albeit subtle but vulnerable and
powerful electrophysiologic substrate impending cardiac rhythm disturbances.
Apparently, the behavior of both non-ischemic and iso-ischemic myocardium in
respect to electric cardiac activity is very similar, at least theoretically.
Some different clinical entities, e.g. arterial hypotension and/or anemia
containing ischemic component, in most cases are free from arrhythmias. This
postulation may be helpful in furthering arrhythmogenicity insights which have
been generated previously. On the contrary, increased blood pressure often
concurs with the supraventricular and/or ventricular arrhythmias; this pattern
also favorably reflects our previous hypothetical assumptions associated with the
mechanisms of arrhythmogenesis. Conclusively, both non-ischemic and iso-ischemic
myocardium may be attributed to nonarrhythmogenic milieu. Nevertheless, the
inventive analysis and more explorative data are required to support the
suggested postulations.
PMID- 28496920
TI - Testing Of Box Lesion By Adenosine.
PMID- 28496921
TI - Atraumatic Lung Hernia: A Rare Complication of Minimally Invasive Surgical Atrial
Fibrillation Ablation.
AB - Lung herniation after minimally invasive thoracoscopic pulmonary vein ablation
has never been described before so far. We report for the first time, of its
incidence in a 62-year-old patient, 6 weeks after a minimally invasive cardiac
surgery (MICS) for atrial fibrillation ablation. We suggest that even after MICS,
a high resolution computerized tomography scan should be performed in patients
presenting with breathing difficulty and chest pain to rule out this condition
too, other than pulmonary vein stenosis.
PMID- 28496922
TI - More Progress in Atrial Fibrillation Education and Management.
PMID- 28496924
TI - Atrial Fibrillation Triggered By Drug-Induced Bradycardia.
AB - Atrial fibrillation (AF) is the most frequently observed arrhythmia in clinical
practice. Many causative factors have been identified from well-known structural
heart disease to less understood triggers. Both sympathetic and parasympathetic
(vagal) stimuli are able to trigger paroxysms of AF. Vagally mediated AF is
especially observed in young healthy subjects and especially during nights when
the heart rate is considerably slow. Tachycardia induced AF is demonstrated and
the possible mechanisms are explained. However, a case of bradycardia induced AF,
thus far, hasn't been reported. Here we present a case of AF induced by severe
bradycardia which was triggered by concomitant use of beta-blockers and
diltiazem.
PMID- 28496923
TI - Emergency Covered Stent Implantation For Rupture Of A Pulmonary Vein After
Balloon Angioplasty For Postinterventional Pulmonary Vein Stenosis.
AB - Pulmonary vein (PV) stenosis is a known complication of PV isolation procedures
for atrial fibrillation. We describe in this report a case of emergency covered
stent implantation for rupture of a PV after balloon angioplasty for
postinterventional PV stenosis occlusion. Focus is on stent implantation and on a
novel aspect of magnetic resonance imaging for postprocedural outcome evaluation.
A focused review of the current literature regarding ongoing limitations of PV
stenosis treatment is provided.
PMID- 28496919
TI - Structural and Functional Remodeling of the Left Atrium: Clinical and Therapeutic
Implications for Atrial Fibrillation.
AB - Atrial fibrillation (AF) is the most commonly encountered arrhythmia in clinical
practice. Despite advances in our understanding of the pathophysiology of this
complex arrhythmia, current therapeutic options remain suboptimal. This review
aimed to delineate the atrial structural and functional remodeling leading to the
perpetuation of AF. We explored the complex changes seen in the atria in various
substrates for AF and the therapeutic options available to prevent these changes
or for reverse remodeling. Here we also highlighted the emerging role of
aggressive risk factor management aimed at the arrhythmogenic atrial substrate to
prevent or retard AF progression.
PMID- 28496925
TI - Cryoballoon versus Radiofrequency Ablation for Atrial Fibrillation: A Meta
analysis of 16 Clinical Trials.
AB - Introduction: We aimed to study the procedural characteristics, efficacy and
safety of cryoballoon ablation (CBA) versus radiofrequency ablation (RFA) for
catheter ablation of paroxysmal atrial fibrillation (AF). Methods: A systematic
literature search was performed using PubMed, EMBASE, Web of Science, and
Cochrane Central Register of Controlled Trials to clinical trials comparing CBA
and RFA for AF. Outcomes were evaluated for efficacy, procedure characteristics
and safety. For each study, odd ratio (OR) and 95% confidence intervals (CIs)
were calculated for endpoints for both approaches. Results: We analyzed a total
of 9,957 participants (3,369 in the CBA and 6,588 in RFA group) enrolled in 16
clinical trials. No significant difference was observed between CBA and RFA with
regards to freedom from atrial arrhythmia at 12-months, recurrent atrial
arrhythmias or repeat catheter ablation. CBA group had a significantly higher
transient phrenic nerve injury (OR 14.19, 95% CI: 6.92-29.10; p<0.001) and
persistent phrenic nerve injury (OR 4.62, 95% CI: 1.97-10.81; p<0.001); and a
significantly lower pericardial effusion/cardiac tamponade (OR 0.43, 95% CI: 0.26
0.72; p=0.001), and groin site complications (OR 0.60, 95% CI: 0.38-0.93;
p=0.02). No significant difference was observed in overall complications,
stroke/thromboembolic events, major bleeding, and minor bleeding. Conclusion: CBA
was non-inferior to RFA for catheter ablation of paroxysmal AF. RF ablation was
associated with a higher groin complications and pericardial effusion/cardiac
tamponade, whereas CBA was associated with higher rates of transient and
persistent phrenic nerve injury.
PMID- 28496926
TI - Novel Ventricular Repolarization Indices in Patients with Coronary Slow Flow.
AB - Background: Coronary slow flow (CSF) phenomenon is described angiographically as
delayed progression of the injected contrast agents through the coronary
arteries. Aim of this study was to analyze ventricular repolarization in CSF
patients by using Tpeak-Tend interval, Tpeak-Tend/QT ratio, Tpeak-Tend/QTc ratio
and other repolarization parameters since these parameters are used as predictors
for ventricular arrhythmogenesis. Materials and Methods: We have retrospectively
analyzed diagnostic coronary angiography results of 160 patients between 2010 and
2014. Patients were divided into two groups according to coronary flow results.
CSF group consisted of 33 female, 82 male patients with mean age 51,9+/-11,5
years. Control group included patients with normal coronary flow; 13 female, 32
male with mean age 50,8+/-11,7 years. In all patients, ventricular repolarization
parameters as well as other associated electrocardiographic intervals were
measured on the twelve-lead surface electrocardiogram. Results: The ventricular
repolarization parameters: QTmax interval, QTmin interval, QTc, QTI, QTcI, JTmax
interval, JTmin interval, JTdispersion and JTIndex were not significantly
different between the groups. However followings parameters differed
significantly between patients and controls; QRS (92,8+/-11,5 msn versus 78,3+/
16,713,40 msn, respectively; p=0.001), T wave (89+/-20,2 msn vs. 73,3+/-13,3 msn
respectively, p=0.001), QT dispersion (26,8+/-17,5 msn vs. 13,5+/-20,4 msn
respectively, p=0.002), JTcorrected (331,6+/-39,8%; vs. 350,1+/-39,7%
respectively; p=0.01). Furthermore; Tpeak-Tend duration (89+/-20,2 msn vs. 73,3+/
13,9 msn respectively; p=0.001), T wave (204+/-34,9 msn vs. 189,2+/-24,8 msn
respectively; p=0.003), Tpeak-Tend/QT ratio (0,22+/-0,05 msn vs. 0,19+/-0,03 msn
respectively, p=0.001) were significantly higher in patients compared to
controls. Tpeak-Tend/QTc ratio was also significantly higher in the CSF group
compared to the controls. (0,21+/-0,05 msn vs. 0,17+/-0,03 msn respectively, p
=0.001). Conclusion: Ventricular repolarization parameters are prolonged in
patients with CSF.
PMID- 28496927
TI - E/Ea For The Prediction of Left Atrial Appendage Thrombi in Patients with Atrial
Fibrillation and Severe Mitral Stenosis.
AB - Atrial fibrillation (AF), left atrial appendage thrombi (LAAT) and subsequent
embolic stroke are the most frequent complications of mitral stenosis .E/Ea is
used traditionally for the assessment of left atrium pressure, and besides AF and
dilated LA size which promotes stasis of blood in LA, high LA pressure also play
a role to clot formation in LA .The receiver operator characteristics (ROC) curve
point-coordinates identified an E:e' value of >= 36.5to have 57.14% sensitivity
and 90.91% specificity for LAAT;We find this ratio relatively specific for
prediction of LAAT, independent of MVA and LA volume, however it needs to be
externally validated.
PMID- 28496928
TI - Idiopathic Paroxysmal Atrio-Ventricular Block. What is The Mechanism?
AB - Idiopathic paroxysmal atrioventricular (AV) block poses a true diagnostic
challenge. What is clear about this entity is the confusion about its definition
and consequently about its etiology. According to certain sources, the diagnosis
of this block requires the lack of a structural cardiac pathology that justifies
the observed manifestations and an absence of electrocardiographic disorders
prior to an episode. The clinical presentation of idiopathic paroxysmal AV block
does not differ from that of another cardiogenic syncope or of a vasovagal
syncope with a significant cardioinhibitory component. With respect to the
mechanism that explains this block, it has been postulated that patients with low
basal adenosine levels exhibit hyperaffinity of the A2 receptors of the AV node.
Variations in plasma adenosine levels may favor episodes of paroxysmal AV block.
The diagnosis of this block is complex and can require years to determine.
Routine electrophysiological examination of these patients is not cost effective
due to the low sensitivity and specificity of this approach. Numerous groups have
supported the use of an implantable loop recorder to substantiate AV block
paroxysms and assess their clinical correlations. Permanent stimulation devices
are utilized to reduce syncopal recurrence.
PMID- 28496930
TI - Percutaneous Vacuum-Assisted Thrombectomy Device Used for Removal of Large
Vegetations on Infected Pacemaker and Defibrillator Leads as an Adjunct to Lead
Extraction.
AB - This case series reports our early experience with a minimally invasive
percutaneous method of safely removing large vegetations during lead extraction
in septic cardiac implantable electronic devices (CIED). Debate exists concerning
the management of vegetations involving these devices. Lead extraction is
mandated for infections, but vegetations may embolize, causing complications.
Surgical debridement is recommended; alternatives include cardiopulmonary bypass,
minimally invasive thoracotomy, or transatrial approaches. The AngioVac device
allows percutaneous right heart bypass and suction removal of vegetations under
echocardiographic and fluoroscopic guidance. This case series describes our first
20 patients, all critically ill with persistent sepsis and vegetations despite
long-term antibiotics. This series includes patients who would not have been
eligible for alternative procedures due to contraindications and highlights the
potential role of this new technology.
PMID- 28496929
TI - Management of Patients with Atrial Fibrillation: Focus on Treatment Options.
AB - Atrial fibrillation (AF) is leading cardiac arrhythmia with important clinical
implications. Its diagnosis is usually made on the basis on 12-lead ECG or 24
hour Holter monitoring. More and more clinical evidence supports diagnostic use
of cardiac event recorders and cardiovascular implantable electronic devices
(CIED). Treatment options in patients with atrial fibrillation are extensive and
are based on chosen rhythm and/or rate control strategy. The use and selected
contraindications to AF related pharmacotherapy, including anticoagulants are
shown. Nonpharmacological treatments, comorbidities and risk factors control
remain mainstay in the treatment of patients with AF. Electrical cardioversion
consists important choice in rhythm control strategy. Much progress has been made
in the field of catheter ablation and cardiac surgery methods. Left atrial
appendage occlusion/closure may be beneficial in patients with AF. CIED are used
with clinical benefits in both, rhythm and rate control. Pacemakers, implantable
cardioverter-defibrillators and cardiac resynchronization therapy devices with
different pacing modes have guaranteed place in the treatment of patients with
AF. On the other hand, the concepts of permanent leadless cardiac pacing, atrial
dyssynchrony syndrome treatment and His-bundle or para-Hisian pacing have been
proposed. This review summarizes and discusses current and novel treatment
options in patients with atrial fibrillation.
PMID- 28496931
TI - Safety of The Direct Oral Anticoagulant Edoxaban for Atrial Fibrillation After
Cardiac Surgery: Pilot Study.
AB - Direct oral anticoagulants have recently been recommended for non-valvular atrial
fibrillation, but have rarely been studied in the field of cardiac surgery. We
prospectively investigated the safety of edoxaban, a novel oral anticoagulant,
for use in cardiac surgery patients with postoperative atrial fibrillation
(POAF), which is the most common complication of cardiac surgery and can lead to
stroke. The subjects were adult cardiac surgery patients with POAF who received
oral edoxaban for 2 months in an open-label pilot study. The primary endpoint was
cerebrovascular/bleeding events up to 2 months, while the secondary endpoints
were hemoglobin, prothrombin time, and activated partial thromboplastin time.
There were no cerebrovascular or bleeding events during edoxaban treatment and
the test drug was not discontinued by any patient. There was no macroscopic
hematuria and hemoglobin did not decrease, being significantly higher than the
baseline level after 2 months. The prothrombin time was significantly prolonged
from 1 week to 2 months and the activated partial thromboplastin time was
significantly prolonged from 1 day to 2 months. Echocardiography detected
pericardial effusion in 1 patient, but hemoglobin did not decrease and the
effusion improved with diuretic therapy. In conclusion, despite the limited
sample size of this pilot study, it was demonstrated that edoxaban does not
induce bleeding in patients with POAF after cardiac surgery, suggesting that it
is safe to perform a large-scale efficacy study of edoxaban as anticoagulant
therapy for POAF.
PMID- 28496932
TI - Mobitz Type 2 AV Block Dissolved With Contrast Injection.
AB - There are many cases in the literature concerning the occurence of
atrioventricular block in acute myocardial infarction. The prevelance and
management of AV block in the setting of chronic myocardial ischemia remains
unclear. Our case presented with stable angina pectoris. Treadmill test revealed
Mobitz Type 2 AV block which disappeared with contrast injection and re-occured
after injection during PCI.
PMID- 28496933
TI - Internet Survey: Health Screening in Sports.
AB - While cardiovascular screening protocols exist, they have been focused on
teenaged and college aged athletes versus adult athletes. To assess community
awareness of health screening as related to adult athletes, we have created an
internet questionnaire (QN). The survey was posted through social media (e.g.
Facebook, Reddit, Flotrack and Active), for 11 months, that queried sports
history, medical history, and symptoms while playing sports. A total of 3,750
respondents (R) answered the questionnaire, 2,776 male and 974 female. Age range:
18-83 yrs, avg: 33.7+/-11.22 yrs, median: 31 yrs. Seventy four per cent of R
(2,775/3,750) reported having at least one of the following symptoms while
playing sports: dizziness, blacking/passing out, racing heartbeat, or chest pain,
and 13.5% (505/3,750) of R reported two or more. 62.3% (1,730/2,775) did not
recall having symptoms. This underreporting was a result of "no one asking" 49.5%
(857/1,730); "not answering after being asked" 28.2% (488/1,730), and "not
telling the truth" 22.2% (384/1,730). Of interest, 97.1% (3,642/3,750) want a
screening QN; 95.8% (3,592/3,750) want pre-screening by an MD. Prior to sports,
only 22.9% (857/3,750) were required to answer a QN vs 38.0% (1,424/3,750) had a
physical exam (PE); 14.9% (560/3,750) of individuals had both PE and QN. We
conclude that adult participants in sports commonly experience symptoms but do
not report them. Nearly all respondents favor participating in a screening
questionnaire that would assess for cardiovascular problems.
PMID- 28496934
TI - Catheter Ablation for Persistent and Long-Standing Persistent Atrial
Fibrillation.
AB - Persistent and long-standing persistent atrial fibrillation evolves from complex
arrhythmogenic substrate and sources. Multiple studies have shown improved
freedom from arrhythmia recurrences if sinus rhythm had been restored during the
index ablation; however, such harder procedural endpoint requires laborious
stepwise approach almost invariably pursuing non-pulmonary-vein sources. Longer
term conversion of persistent atrial fibrillation into sinus rhythm is associated
with significant improvement in major indices of hemodynamic and functional
status; these indices also represent major predictors of cardiovascular
mortality. Optimal ablation techniques and strategies preserving most of the
individual potential for functional improvement need to be established.
PMID- 28496935
TI - Catheter Ablation of Incisional Atrial Tachycardia.
AB - Tachycardias after atrial incisions represent frequent and serious problem. The
majority of them are based on a re-entry electrical activation around a
combination of anatomic and surgically created obstacles. Considering significant
progress of cardiovascular surgery during the last decade along with potential
large amount of open-heart procedures in the near future the number of incisional
tachycardias has a tendency to increase. The aim of this work was to quantify the
magnitude of the problem, characterize the tachycardias after different surgical
operations and to analyze possible interventional treatment strategies. Nowadays
evolution of mapping and ablation technologies may contribute to radically
treatment of this type of arrhythmias while there are still a lot of issues that
should be solved to improve the results of interventional treatment of incisional
tachycardias.
PMID- 28496936
TI - Strategies to Improve Safety and Efficacy of Atrial Fibrillation Ablation Using
Electrode Multipolar Phased RF PVACTM Catheter: a Case Report.
AB - Phased radiofrequency ablation with a single catheter technique, using a 9
electrode circumferential catheter, is a viable approach to pulmonary vein
isolation for the treatment of atrial fibrillation. However, creating effective
transmural lesions with such technique, while avoiding serious complications like
atrioesophageal fistula, can be difficult. This case illustrates a challenging
scenario, where catheter maneuvers fail to allow safe radiofrequency delivery,
due to esophageal temperature rise, despite extensive navigating maneuvers.
Changing the bipolar-to-unipolar ratio of energy delivery, from 2:1 to 4:1,
allowed the creation of effective lesions, avoiding excessive increase in
esophageal temperature.
PMID- 28496937
TI - Amiodarone-Induced Third Degree Atrioventricular Block and Extreme QT
Prolongation Generating Torsade Des Pointes in Paroxysmal Atrial Fibrillation.
AB - Amiodarone is still the most potent antiarrhythmic drug in the prevention of life
threatening ventricular arrhythmias and demonstrates a very low incidence of
torsade de pointes. An unusual case of an 81-year-old woman who developed serious
abnormalities of the conduction system of the heart and torsade des pointes
during intravenous infusion of amiodarone for the treatment of paroxysmal atrial
fibrillation is described. To the best of our knowledge, this is the first case
showing an association of intravenous amiodarone-induced third degree
atrioventricular block and extreme QT interval prolongation generating torsade
des pointes in a patient with paroxysmal atrial fibrillation who required an
implantable cardioverter-defibrillator. Currently, amiodarone is still one of the
few remaining treatment options for the medical therapeutic management of serious
ventricular arrhythmias and to reduce the incidence of atrial fibrillation
without increasing mortality or sudden cardiac death rates in heart failure
patients like our elderly present patient. Nevertheless, we have to keep in mind
that intravenous amiodarone may generate serious abnormalities of the conduction
system of the heart and lethal ventricular arrhythmias in certain patients.
PMID- 28496939
TI - Happy Holidays!!!
PMID- 28496938
TI - Brugada Syndrome:Risk Stratification And Management.
AB - The Brugada syndrome (BrS) is an arrhythmogenic disease associated with an
increased risk of ventricular fibrillation and sudden cardiac death. The risk
stratification and management of BrS patients, particularly of asymptomatic ones,
still remains challenging. A previous history of aborted sudden cardiac death or
arrhythmic syncope in the presence of spontaneous type 1 ECG pattern of BrS
phenotype appear to be the most reliable predictors of future arrhythmic events.
Several other ECG parameters have been proposed for risk stratification. Among
these ECG markers, QRS-fragmentation appears very promising. Although the value
of electrophysiological study still remains controversial, it appears to add
important information on risk stratification, particularly when incorporated in
multiparametric scores in combination with other known risk factors. The present
review article provides an update on the pathophysiology, risk stratification and
management of patients with BrS.
PMID- 28496940
TI - Complete genome sequence of bacteriochlorophyll-synthesizing bacterium
Porphyrobacter neustonensis DSM 9434.
AB - The genus Porphyrobacter belongs to aerobic anoxygenic phototrophic bacteria
cluster. Porphyrobacter neustonensis DSM 9434 was isolated from a eutrophic
freshwater pond in Australia, and is able to synthesize Bacteriochlorophyll a as
well as grow under aerobic conditions. It is the type species of the genus
Porphyrobacter. Here we describe the characteristics of the strain DSM 9434,
including the genome sequence and annotation, synthesis of BChl a, and metabolic
pathways of the organism. The genome of strain DSM 9434 comprises 3,090,363 bp
and contains 2,902 protein-coding genes, 47 tRNA genes and 6 rRNA genes. Strain
DSM 9434 encodes 46 genes which participate in BChl a synthesis and this
investigation shed light on the evolution and functional implications regarding
bacteriochlorophyll synthesis.
PMID- 28496941
TI - Chromosomal features of Escherichia coli serotype O2:K2, an avian pathogenic E.
coli.
AB - Escherichia coli causing infection outside the gastrointestinal system are
referred to as extra-intestinal pathogenic E. coli. Avian pathogenic E. coli is a
subgroup of extra-intestinal pathogenic E. coli and infections due to avian
pathogenic E. coli have major impact on poultry production economy and welfare
worldwide. An almost defining characteristic of avian pathogenic E. coli is the
carriage of plasmids, which may encode virulence factors and antibiotic
resistance determinates. For the same reason, plasmids of avian pathogenic E.
coli have been intensively studied. However, genes encoded by the chromosome may
also be important for disease manifestation and antimicrobial resistance. For the
E. coli strain APEC_O2 the plasmids have been sequenced and analyzed in several
studies, and E. coli APEC_O2 may therefore serve as a reference strain in future
studies. Here we describe the chromosomal features of E. coli APEC_O2. E. coli
APEC_O2 is a sequence type ST135, has a chromosome of 4,908,820 bp (plasmid
removed), comprising 4672 protein-coding genes, 110 RNA genes, and 156
pseudogenes, with an average G + C content of 50.69%. We identified 82 insertion
sequences as well as 4672 protein coding sequences, 12 predicated genomic
islands, three prophage-related sequences, and two clustered regularly
interspaced short palindromic repeats regions on the chromosome, suggesting the
possible occurrence of horizontal gene transfer in this strain. The wildtype
strain of E. coli APEC_O2 is resistant towards multiple antimicrobials, however,
no (complete) antibiotic resistance genes were present on the chromosome, but a
number of genes associated with extra-intestinal disease were identified.
Together, the information provided here on E. coli APEC_O2 will assist in future
studies of avian pathogenic E. coli strains, in particular regarding strain of E.
coli APEC_O2, and aid in the general understanding of the pathogenesis of avian
pathogenic E. coli.
PMID- 28496942
TI - TGF-beta1 polymorphisms -509 C>T and +915 G>C and risk of pancreatic cancer.
AB - BACKGROUND: Ninety percent of pancreatic cancer patients have less than 5-year
overall survival and approximately 50% of cases were diagnosed with metastasis in
the time of admission. Previous evidences have demonstrated the strong
association between TGF-beta1 variations and cancer susceptibility so far.
METHODS: A total of 78 patients with pancreatic cancer and 94 healthy controls
were enrolled in this case- control study between 2007 and 2012. Genomic DNA was
isolated from peripheral blood samples according to phenol chloroform extraction.
The genotypes of TGF-beta1 rs rs1800469 and rs1800471 were determined using the
polymerase chain reaction-restriction fragment length polymorphism method.
RESULTS: The mean age of cases and the control group were 64.50 +/- 13.718 and
40.12 +/- 16.001, respectively. For polymorphism -509 C>T, the frequency of TT
genotype were 31 (33.0), CT, 47(50) and CC, 16 (17) in control and 19 (24.4), 45
(57.7) and 14 (17.9) in cases respectively. In position +915 G>C, the frequency
of GG genotype was 84 (89.4) and GC, 10 (10.6) in control and 71 (91.0) and 7 (9)
in cases, respectively. We did not observe any significant differences in the
genotype and allele frequencies of the TGF-beta1-509 C>T (rs1800469) and codon
+915 G>C (rs1800471) between the two study groups (P>0.05). CONCLUSION: we found
that TGF-beta1 gene polymorphisms rs1800469 and rs1800471 might not play a role
in pancreatic cancer susceptibility in Iranian population.
PMID- 28496943
TI - Research in Iran: An Overview.
PMID- 28496945
TI - Gestational Exposure to Silymarin Increases Susceptibility of BALB/c Mice Fetuses
to Apoptosis.
AB - BACKGROUND: Silymarin is a flavonolignan that has been the subject of research to
evaluate the beneficial properties for decades. Silymarin has been known for its
potent cytoprotective, hepatoprotective and antioxidant activities. The goal of
the present study was to gain a deeper understanding of possible molecular
mechanisms of apoptosis of the injuries induced by silymarin on BALB/c mice
fetuses. METHODS: The present experimental study was carried out in virgin female
BALB/c mice. The animals were divided randomly into 4 groups. Three test groups
were injected intraperitoneally with silymarin at doses of 50, 100 and 200
mg/kg/day during gestational days 6-15. The control group received the solvent by
the same route at equivalent volume. Western blot analysis was conducted to
determine the levels of caspase-3 and caspase-8 in fetal heart, kidney, lungs and
brain tissue. RESULTS: The results of this study showed that silymarin
administration during organogenesis at doses of 50, 100 and 200 mg/kg can
significantly increase the protein levels of caspase-3 and 8 in heart, kidneys
and brain tissues of mice fetuses compared with control group (p<0.001).
Silymarin exposure could not change the level of apoptotic markers in fetal lung
tissue. CONCLUSION: According to the results, programmed cell death, especially
via the intrinsic pathway, plays a pivotal role in the pathogenesis of silymarin
induced malformations in some tissue including heart, kidneys and brain. More
studies are needed to determine other molecular mechanisms underlying silymarin-
induced embryo toxicity.
PMID- 28496944
TI - Current State of Cartilage Tissue Engineering using Nanofibrous Scaffolds and
Stem Cells.
AB - Cartilage is an avascular, aneural, and alymphatic connective tissue with a
limited capacity caused by low mitotic activity of its resident cells,
chondrocytes. Natural repair of full thickness cartilage defects usually leads to
the formation of fibrocartilage with lower function and mechanical force compared
with the original hyaline cartilage and further deterioration can occur. Tissue
engineering and regenerative medicine is a promising strategy to repair bone and
articular cartilage defects and rehabilitate joint functions by focusing on the
optimal combination of cells, material scaffolds, and signaling molecules. The
unique physical and topographical properties of nanofibrous structures allow them
to mimic the extracellular matrix of native cartilage, making an appropriate
resemblance to induce cartilage tissue regeneration and reconstruction. To
improve simulation of native cartilage, the incorporation of nanofibrous
scaffolds with suitable corresponsive cells could be effective. In this review
article, an attempt was made to present the current state of cartilage tissue
engineering using nanofibrous scaffolds and stem cells as high proliferative
immune privilege cells with chondrogenic differentiation ability. The
comprehensive information was retrieved by search of relevant subject headings in
Medline/Pubmed and Elsevier databases.
PMID- 28496946
TI - Alpha Alumina Nanoparticle Conjugation to Cysteine Peptidase A and B: An
Efficient Method for Autophagy Induction.
AB - BACKGROUND: Autophagy as a cellular pathway facilitates several immune responses
against infection. It also eliminates invading pathogens through transferring
content between the cytosol and the lysosomal vesicles and contributes to the
cross-presentation of exogenous antigens to T lymphocytes via MHC class I
pathway. Autophagy induction is one of the main targets for new drugs and future
vaccine formulations. Nanoparticles are one of the candidates for autophagy
induction. Cysteine Peptidase A (CPA) and Cysteine Peptidase B (CPB) are two
members of papain family (Clan CA, family C1) enzyme that have been considered as
a virulence factor of Leishmania (L.) major, making them suitable vaccine
candidates. In this research, Leishmania major cysteine peptidase A and B (CPA
and CPB) conjugation to alpha alumina nanoparticle was the main focus and their
entrance efficacy to macrophages was assessed. METHODS: For this purpose, CPA and
CPB genes were cloned in expression vectors. Related proteins were extracted from
transformed Escherichia coli (E. coli) and purified using Ni affinity column.
Alpha alumina nanoparticles were conjugated to CPA/CPB proteins using
Aldehyde/Hydrazine Reaction. Autophagy induction in macrophages was assessed
using acridine orange staining. RESULTS: CPA/CPB protein loading to nanoparticles
was confirmed by Fourier Transform Infrared Spectroscopy. alpha-alumina
conjugated CPA/CPB antigen uptake by macrophages at different concentrations was
confirmed using fluorescence microscope and flowcytometry. Highly efficient
CPA/CPB protein loading to alpha-alumina nanoparticles and rapid internalization
to macrophages introduced these nanocarriers as a delivery tool. Acridine orange
staining demonstrated higher autophagy induction in CPA/CPB protein conjugated
with alpha-alumina nanoparticles. CONCLUSION: alpha-alumina nanoparticles may be
a promising adjuvant in the development of therapeutic leishmania vaccines
through antigen delivery to intracellular compartments, induction of autophagy
and cross presentation to CD8 lymphocytes.
PMID- 28496947
TI - Efficient Media for High Lipase Production: One Variable at a Time Approach.
AB - BACKGROUND: Lipase enzymes have applications in a wide range of industries. A
crucial determining factor of industrial prices of these enzymes is the culture
media composition that is constantly under review by researchers. In this work,
for maximum lipase production by Bacillus sp. ZR-5, culture media compositions
were optimized using "one variable at a time" strategy. METHODS: For this
purpose, the culture medium parameters such as low and high cost carbon and
nitrogen sources, substrates and incubation times were evaluated. RESULTS:
Maximum lipase activity was achieved after 24 hr of incubation with 1.5% of
glucose syrup (1600+/-69.1 u/mg), 1% of fish powder (1238+/-36.7 u/mg) and olive
oil (1407+/-2.1 u/mg) as low cost carbon and nitrogen sources and substrate,
respectively. CONCLUSION: Our results show a significant increase in lipase
activity with usage of low cost sources; this could help in reducing the media
prices for industrial application of lipase enzyme.
PMID- 28496948
TI - Evaluation of IgY Antibody as a Polyspecific Coombs-Reagent.
AB - BACKGROUND: During the last twenty years, the extraction of specific egg yolk
(IgY) antibodies from the immunized chickens has been accepted as a useful
alternative to the immunization of mammals. The aim of the present study was
immunizing the chickens with Human Umbilical Cord Serum (HUCS) and the extraction
of specific anti-human globulins (IgG, C3b, and C3d) antibodies from egg yolk in
order to obtain polyspecific Coombs reagent. METHODS: The novelty of this work
was the achievement of a polyclonal reagent through a very cheap alternative
method in accordance with all ethical regulations required for obtaining it.
Three Leghorn hens (21 weeks old) were immunized four times for a period of 66
days with 20uL of HUCS mixed with PBS/FCA or FIA each time. The extraction of IgY
antibodies was performed according to the method of lipid precipitation of yolk
and using water soluble fraction as the reagent material. The resulting IgY
antibody was characterized by SDS-PAGE and immunoelectrophoresis and tested for
the presence of hetero-agglutinins by means of direct agglutination using human
erythrocytes of all blood groups treated with 0.1% papain and for indirect Coombs
test to evaluate its specificity to fractions (C3b, C3d, C4d) of human complement
and human IgG, respectively. RESULTS: Our findings show, that, the reagent
obtained contains IgY and other 3 proteins (SDS-PAGE), and reacts specifically
with plasma proteins, that migrate in beta and Upsilon regions. In
immunoelectrophoresis, in addition, there is the presence of low hetero
agglutinins levels in IgY-preparation (3 lots), and the possibility to produce
high amount (more than 500 ml/egg) of polyspecific Coombs-reagent in chickens is
also discussed. CONCLUSION: IgY-preparation (3 lots), and the possibility to
produce high amount (more than 500 ml/egg) of polyspecific Coombs-reagent in
chickens with the originality to achieve a polyclonal reagent through a very
cheap alternative method in accordance with all ethical regulations required for
obtaining it, was also discussed.
PMID- 28496949
TI - The Effect of Interactions of Single Nucleotide Polymorphisms of APOA1/APOC3 with
Food Group Intakes on the Risk of Metabolic Syndrome.
AB - BACKGROUND: The aim of this study was to examine the interaction of dietary food
groups and genetic variants of APOA1/APOC3, relative to Metabolic Syndrome (MetS)
risk in adults. METHODS: In this matched nested case-control study, 414 MetS
subjects and 414 controls were selected from among participants of Tehran Lipid
and Glucose Study. Dietary intake was assessed with the use of a valid and
reliable semi-quantitative food frequency questionnaire. Single Nucleotide
Polymorphisms (SNPs), APOA1 (rs670, -75G>A and rs5069, +83C>T/APOC3 rs5128
C3238>G) were genotyped by the conventional polymerase chain reaction and
restriction fragment length polymorphism. RESULTS: The mean (SD) of age was 40.7
(13) and 41.2 (13) years in male cases and controls versus 44.0 (11) and 44.0
(12) years in female case and controls. A significant interaction between intake
quartiles of the sugar group and APOA1 combined group (GA+AA/CT+TT) SNPs was
found; The ORs for these genotype carriers were (1, 0.44, 0.36, 0.23; P
trend<0.001) in quartiles of intake, relative to other combined genotypes (P
interaction=0.02). MetS risk appeared to be increased significantly in higher
quartiles of sweet beverages and fish intakes in the GA+AA/CT+TT/CC genotypes of
APOA1/APOC3 SNPs, compared to other genotypes (P interaction=0.01). The combined
effect of genotypes of APOC3/APOA1 showed further decrease in MetS risk in higher
quartiles of sugar group intakes (OR: 1, 0.24, 0.26, 0.14, P trend=0.001)
relative to other combinations (P interaction=0.008). CONCLUSION: Results
obtained demonstrate that some dietary food groups (sugar, fish, and sweet
beverages) modulate the effect of APOA1/APOC3 SNPs in relation to MetS risk.
PMID- 28496950
TI - Development of Flow Cytometry-Fluorescent In Situ Hybridization (Flow-FISH)
Method for Detection of PML/RARa Chromosomal Translocation in Acute Promyelocytic
Leukemia Cell Line.
AB - BACKGROUND: Acute Promyelocytic Leukemia (APL) is a subclass of acute myeloid
leukemia. The chromosomal aberration in 95% of APL cases is t(15; 17) (q22; q21),
which prevents cell differentiation. Characterization of the underlying molecular
lesion is valuable in determining optimal treatment strategy. The goal of this
study was to develop a new and powerful Flow- FISH technique to detect the long
isoform (L) of PML-RARa fusion transcript in NB4 cell line. METHODS: To achieve
the best condition for fixation, two different fixatives including 2%
paraformaldehyde and 75% ethanol were used. 0.2% Triton X-100 and 0.2% saponin
were used for the permeabilization step .In hybridization, a wide range of times
and temperatures were used and probe was designed in FRET system. Results were
confirmed by fluorescent microscope assay and reverse transcription PCR. RESULTS:
In the present study, a novel technique was successfully optimized that combines
in situ hybridization with flow cytometry to detect the presence of PML-RARa
transcript. Using standard fixation and permeabilization protocol of 2% PFA and
0.2% saponin gave the best fluorescent results in flow cytometry. Also, results
indicated that the optimum time and temperature for hybridization was 2 hr at 42
degrees C. The results of reverse transcription PCR and fluorescent microscopy
confirmed the presence of PML-RARa transcript. CONCLUSION: The concordance
between the results of Flow-FISH and those of two other techniques including
reverse transcription PCR and FISH indicated that this method would be applicable
as a diagnostic test for APL in clinical samples and MRD monitoring.
PMID- 28496951
TI - Can Aptameric Ligands Specific to Plasma Coagulation Factor VII Bind the
Recombinant Form with High Affinity: Affinity Measurement by Fluorescence Method.
AB - BACKGROUND: Among diverse protein purification systems, affinity chromatography
is the most attractive one in the purification process of coagulation factors.
Coagulation factor VII is a plasma serine protease that has a significant role in
natural human hemostasis and its recombinant form such as AryoSevenTM, has been
applied in clinical treatment of bleeding disorders. Immunoaffinity
chromatography is the purification method of choice that is currently applied in
the development of coagulation factor VIIa products. Aptamers as nucleic acid
based affinity ligands are more promising than monoclonal antibodies. In
addition, DNA aptamers are more acceptable than RNA ones in this regard. METHODS:
In this study, two of the aptameric DNA oligonucleotides that showed acceptable
affinities for purification of coagulation factor VIIa from plasma, were selected
to evaluate their affinity against Aryoseven. A serial dilution of fluorescence
labeled aptamers was incubated against the concentration of 1 nM from Aryoseven.
Then, a fluorescence index was calculated according to the fluorescence intensity
data measured from test and control samples. The dissociation constant of
aptamers was calculated according to the fluorescence index using Prism5
software. RESULTS: Results showed that the binding affinity of the 44 nucleotide
aptamer was more than 81 nucleotide aptamer sequence. As a result, this aptamer
could be optimized in order to develop aptamer based affinity chromatography
process for this form of recombinant coagulation factor VIIa. DISCUSSION:
Aptamers with shorter length of sequence could show higher affinity in target
binding, as they could adapt more easily to suitable conformation according to
target interaction. However, it should be considered that the selectivity of
affinity ligands is also important for target purification and analytical
applications.
PMID- 28496952
TI - HIV Programs in Iran (Persia), Iraq and Saudi Arabia: A Brief Review of Current
Evidence in West and Southwest Asia.
AB - BACKGROUND: In Western and Southwest Asia, literature is not documented on human
immunodeficiency virus (HIV) programs in Iran, Iraq and Saudi Arabia. The present
study is the first brief review that describes HIV programs in these three
neighboring countries. METHODS: Data regarding the evidence of HIV programs were
gathered through a systematic literature searching. English publications were
retrieved through searching online scientific databases. Grey literature was also
searched online. The review was based on the studies related to the last decade.
FINDINGS: Systematic searching resulted in retrieving 21,948 studies but only 21
studies were relevant to the study aim. The review findings indicated that Iran
has provided a nationwide sero-surveillance data system and has identified its
key populations. Detecting HIV prevalence has been limited to case-finding in
Iraq and Saudi Arabia. However, strategic plans for HIV have been provided in the
three countries. HIV education, knowledge and support have been provided but
still needs consideration in the three countries especially in Iraq. The low
coverage of antiretroviral therapy (ART) has remained a critical gap in the
provision of comprehensive HIV programs in these three countries. This issue has
been followed by the lack of opiate substitution therapies for drug dependents
and injecting drug users in Iraq and Saudi Arabia. Condom promotion and voluntary
HIV counselling and testing have been provided for at-risk groups in the three
countries but need more nationwide coverages. However, needle and syringe
programs (NSPs) have been only provided in Iran. CONCLUSION: The review concluded
that the provision of effective HIV programs should address training human
resources and infrastructural development. This issue should be facilitated by
international collaborations and governmental supports.
PMID- 28496953
TI - Estrogen and Progesterone Replacement Therapy Prevent Methamphetamine-Induced
Synaptic Plasticity Impairment in Ovariectomized Rats.
AB - BACKGROUND: Methamphetamine (METH) is one of the most popular psychostimulants
which produce long lasting learning and memory impairment. Previous studies have
indicated that estrogen and progesterone replacement therapy attenuate cognitive
impairment against a wide array of neurodegenerative diseases. Present study was
designed to figure out the effects of estrogen, progesterone alone or in
combination, on early long-term potentiation (E-LTP) at the cornu ammonis (CA1)
area of the hippocampus in METH-exposed ovariectomized (OVX) rat. METHODS: Twenty
one days after ovariectomy, the OVX rats received vehicle, estrogen [1 mg/kg,
intraperitoneal (IP)] or progesterone (8 mg/kg, IP) and co-administration of
estrogen plus progesterone during 14 consecutive days. On the 28th day, animals
were exposed to neurotoxic METH regimens [four injections 6 mg/kg, subcutaneous
(SC), 2 h intervals] 30 min after the hormones replacement. Finally, we
investigated the effect of those ovarian hormones on synaptic plasticity using in
vivo extracellular recording in the CA1 area of the hippocampus 2 days after last
treatment. FINDINGS: The findings showed that the induction and maintenance phase
of E-LTP was impaired in the METH exposed animals compared to the saline group.
Data from this study demonstrated that treatment with estrogen and progesterone
showed a significant facilitation for induction and enhancement of the
maintenance of LTP in animals that received METH. In addition, co-administration
of estrogen plus progesterone did not significantly affect the hippocampal
synaptic plasticity in METH-exposed OVX rats in comparison with METH-exposed
animals that received vehicle injections. CONCLUSION: The present findings
provide new insight about treatment with ovarian hormones on synaptic plasticity
deficits induced by METH.
PMID- 28496954
TI - Sexual Risk Behaviors Constructed in Iranian Women's Life with Substance Use
Disorders: A New Implication of Human Ecological Theory.
AB - BACKGROUND: Drug abuse is one of the important variables influencing protective
sexual behavior. The objective of this study was to explore how risky sexual
behaviors develop in drug abusing women using human ecological theory. METHODS:
In this study, we used a descriptive exploratory approach. The participants were
32 drug abusing women from two of the selected drop-in centers (DICs) in south
Tehran, Iran, where we could have access to a vast number of female drug users.
Data was collected using semi-structured face-to-face interviews. Qualitative
content analysis was used to analyze the data using Graneheim and Lundman
procedure. FINDINGS: Risky sexual behavior in drug use disorders in women was
found in four themes with thirteen emerged; sexual untaught at micro-system with
two subthemes "unsafe home" and "drop out of school", Perception of differences
at meso-system with three subthemes "lack of link between family and school",
"doing manly behavior" and "low awareness of health puberty than peers",
inappropriate marriages at exo-system with three subthemes "stigma", "fear of
losing love relationship" and "self-devotion", marginalization at macro-system
with four subthemes "barrier access to rights", "selling sex as a tool of
security", "lack of belief as a sex worker" and "mistrust and doubt partner"
using implication of human ecological theory. CONCLUSION: Findings suggest that
strategies supporting the discovery of risky sexual behaviors in drug use
disorders in women are important in order to provide counseling and education to
form their decisions toward safety sex.
PMID- 28496955
TI - Estimating the Size and Age-gender Distribution of Women's Active Social
Networks.
AB - BACKGROUND: Network Scale-up (NSU) method is an indirect method for the
estimation of hidden behaviors. In NSU, respondents are asked about the number of
members they know from a subpopulation of interest (e.g., injecting drug user)
and assume that the prevalence of risky behavior in the networks of a random
sample of respondents is similar to that of the population. However, first, we
need to identify the total number of people each respondent knows [the social
network size (C)]; Moreover, certain risky behaviors happen in particular age and
gender groups. Our aim was to determine the size and age-gender distribution of
female networks. METHODS: This cross-sectional study was conducted in the city of
Kerman, Iran. A total sample of 1275 women was recruited using multistage
sampling. In this study, 25 first names were selected as reference groups.
Participants were asked how many people they know with the selected names. The
respondent's answers were categorized into eight separate age-gender subgroups
and C was estimated for each subgroup. FINDINGS: The results of this study showed
that, on average, each Kermanian woman knows about 234 people and about two
thirds of them are female (82 males and 152 females); moreover, participants were
more likely to communicate with their peers. The majority of males (88%) known by
Kermanian women were in young and middle age groups; in contrast the female young
and middle age groups, who are at reproductive age, form only 45% of the female
part of their networks. CONCLUSION: We have seen that the age-gender distribution
of the networks is not the same as that of the general population. Our figures
can be applied in NSU studies focusing on risky behaviors of particular age and
gender groups.
PMID- 28496956
TI - Effects of Opium Addiction and Cigarette Smoking on Hematological Parameters.
AB - BACKGROUND: The aim of the present study was to investigate the effects of opium
addiction and cigarette smoking on the complete blood count (CBC). METHODS:
Eighty-six male subjects, including 31 opium-addicted cigarette smokers (OACS),
19 opium-addicted non-cigarette smokers (OANCS), 17 non-opium-addicted cigarette
smokers (NOACS), and 19 non-opium-addicted non-cigarette smokers (NOANCS)
participated in this study. The CBC test was measured in all individuals.
FINDINGS: The OACS had significantly higher white blood cell (WBC), lymphocyte,
and red blood cell (RBC) count but lower in mean corpuscular volume (MCV)
compared to NOANCS. The OANCS had significantly higher lymphocyte in comparison
with NOACS. Our results demonstrated that the number of WBC, lymphocytes, and RBC
were significantly higher, while, MCV was lower in OANCS subjects when compared
to NOACS. The OACS had significantly higher level of lymphocyte in comparison
with NOACS. The mean number of lymphocyte in OANCS was found significantly higher
than NOACS. The smokers were shown to have significantly higher levels of WBC
compared to NOANCS. CONCLUSION: Our results showed that opium-addiction,
especially when associated with cigarette smoking, has intensive effects on
hematological factors and these alteration might leads to greater risk for
developing atherosclerosis, cardiovascular diseases, and imbalance in immune
system.
PMID- 28496957
TI - Injecting and Sexual Networks and Sociodemographic Factors and Dual HIV Risk
among People Who Inject Drugs: A Cross-sectional Study in Kermanshah Province,
Iran.
AB - BACKGROUND: Few studies suggest that social network factors, including size of
sexual network may associate with drug-related and sexual high-risk behaviors.
The objective of this study is to investigate injecting and sexual networks and
sociodemographic factors that might be associated with dual HIV risk (DHR) among
people who inject drug (PWID). METHODS: The data from a cross-sectional study of
455 PWID that were recruited through peer-referral sampling were used in this
study. The data were collected using a structured questionnaire consisted of
modules on sociodemographic characteristics, sexual and injection-related risk
behaviors during 12 months before the interview. DHR was defined as engaged in
both using a syringe previously used by other PWIDs and unprotected sex during
last 12 months. Data analysis was performed with descriptive and logistic
regression. In final model, we considered variables with P < 0.500 as
statistically significant. Finally, reported adjusted odds ratio (AOR) and
confidence interval (95% CI) for variables that were significant in the final
model. FINDINGS: A total of 455 men who injected drugs participated in this
study. The mean age +/- standard deviation (SD) was 33.2 +/- 7.3 (range 19-58)
years. Overall, the prevalence of DHR In the last 12 months, 38% (95% CI: 18.3
51.2%). Multivariate model showed that regular visit to needle, syringe programs
(NSPs) reduced odd of HDR to 50% when adjusted for other covariates, but still
remained statistically significant (P < 0.050). The odds of reporting DHR was
significantly higher in those >= 2 sex partners and injection partner (P <
0.010). Odds of DHR was higher (AOR: 2.3) among participants who had more than 2
injection per day but was not statistically significant (P > 0.050). CONCLUSION:
DHR was common in PWID in Kermanshah, Iran. Having multiple injecting and sexual
partners increased the odds of engaging in dual risk behaviors, but regular visit
of NSPs can reduce the DHR among PWID.
PMID- 28496958
TI - Prevalence of HIV/AIDS among Iranian Prisoners: A Review Article.
AB - BACKGROUND: Worldwide, prisoners are more at risk of being infected by human
immunodeficiency virus (HIV) as well as hepatitis C and B in comparison with
other risk groups. The combination of acquired immune deficiency syndrome (AIDS),
addiction and prison are factors that threaten the health of our society.
Influence of risky behaviors is so common on transmission of AIDS into prisoners'
bodies. This study used available information and reports to investigate the
prevalence of HIV in Iranian prisons. METHODS: The following review of documents
available in national and foreign databases, a total of 26 studies were
investigated and required information was extracted from both the full papers and
abstracts. FINDINGS: The selected studies differed methodologically in their
sampling method and data collection tools. Within the 26 studies analyzed, there
was a combined study cohort of 39707 people in whom HIV prevalence varied between
0% and 24.40%. CONCLUSION: In this study, HIV prevalence ranged widely among the
prisoners, and in most of these studies, the rate in Iran was higher than that of
other countries. The prevalence of disease was highest among intravenous drug
users. Unless proper preventive and control plans among risk groups such as
prisoners are not implemented in a timely and suitable manner, the risk of
infection in the broader society will increase.
PMID- 28496959
TI - Is Pathological Trading an Overlooked Form of Addiction?
PMID- 28496960
TI - Erratum: Willingness to Receive Treatment for Hepatitis C among Injecting Drug
Users on Methadone Program: Implications for Education and Treatment.
AB - [This corrects the article on p. 90 in vol. 2.].
PMID- 28496961
TI - Mobilization, Isolation and Characterization of Stem Cells from Peripheral Blood:
a Systematic Review.
AB - OBJECTIVES: The purpose of this article is to systematically review the methods
of mobilization, isolation and characterization of stem cells from peripheral
blood and to discuss their potential therapeutic applications for bone tissue
regeneration. MATERIAL AND METHODS: An electronic literature search was performed
through MEDLINE (PubMed) electronic database. The search was restricted to
English language articles published during the last 10 years, from January 2006
to November 2016. RESULTS: In total, 37 literature sources were reviewed, and 11
of the most relevant articles that are suitable to the criteria were selected.
Articles were analysed with data on animals and humans for mobilization,
isolation and characterization of stem cells from peripheral blood. From the
examination of selected articles, the mobilization materials, side effects,
alternatives and factors affecting the extracted amount of mesenchymal stem cells
(MSC) from mobilized peripheral blood of healthy individuals, as well as
characterization of mobilized MSC were reviewed in this article. CONCLUSIONS:
Bone tissue engineering is a potential alternative strategy in bone regeneration
and bone defect repair, however, insufficiency data display in the literature on
potential therapeutic applications of peripheral blood stem cells for bone tissue
regeneration.
PMID- 28496962
TI - Scalloped Implant-Abutment Connection Compared to Conventional Flat Implant
Abutment Connection: a Systematic Review and Meta-Analysis.
AB - OBJECTIVES: The objective was to test the hypothesis of no difference in implant
treatment outcome after installation of implants with a scalloped implant
abutment connection compared to a flat implant-abutment connection. MATERIAL AND
METHODS: A MEDLINE (PubMed), Embase and Cochrane library search in combination
with a hand-search of relevant journals was conducted. No language or year of
publication restriction was applied. RESULTS: The search provided 298 titles.
Three studies fulfilled the inclusion criteria. The included studies were
characterized by low or moderate risk of bias. Survival of suprastructures has
never been compared within the same study. High implant survival rate was
reported in all the included studies. Significantly more peri-implant marginal
bone loss, higher probing depth score, bleeding score and gingival score was
observed around implants with a scalloped implant-abutment connection. There were
no significant differences between the two treatment modalities regarding
professional or patient-reported outcome measures. Meta-analysis disclosed a mean
difference of peri-implant marginal bone loss of 1.56 mm (confidence interval:
0.87 to 2.25), indicating significant more bone loss around implants with a
scalloped implant-abutment connection. CONCLUSIONS: A scalloped implant-abutment
connection seems to be associated with higher peri-implant marginal bone loss
compared to a flat implant-abutment connection. Therefore, the hypothesis of the
present systematic review must be rejected. However, further long-term randomized
controlled trials assessing implant treatment outcome with the two treatment
modalities are needed before definite conclusions can be provided about the
beneficial use of implants with a scalloped implant-abutment connection on
preservation of the peri-implant marginal bone level.
PMID- 28496963
TI - In Vitro Comparison of Biological Effects of Coe-Pak and Reso-Pac Periodontal
Dressings.
AB - OBJECTIVES: The purpose of the present study was to compare the cytotoxicity of
Reso-Pac and Coe-Pak periodontal dressing. MATERIAL AND METHODS: According to ISO
10993-12:2012, 1-, 3- and 7-day extracts of the two periodontal dressings were
prepared in cell culture medium and exposed to the two cultured cell lines. Cell
viability and proliferation at 24 h and 72 h following exposure were evaluated
using quantitative MTT assay. RESULTS: The results showed a significant (P <
0.05) reduction in the viability of cells exposed to the 3- and 7-day Coe-Pak
extracts at 24 h and 72 h compared to the control group (no exposure to the
extract). Reso-Pac extracts slightly decreased cell viability compared to the
control group. Understudy materials showed greater cytotoxicity against human
osteoblast-like compared to the human gingival fibroblast cells. No significant
(P > 0.05) difference was found in the viability of cells exposed to undiluted
(100%) one-day extract and diluted (50%) extract of both understudy materials at
24 h and 72 h after exposure. CONCLUSIONS: Based on the results, Reso-Pac
periodontal dressing has less cytotoxicity than Coe-Pak.
PMID- 28496964
TI - Oral Health Status of Institutionalized Individuals with Intellectual
Disabilities in Lebanon.
AB - OBJECTIVES: To assess the dental status of institutionalized intellectually
disabled individuals in Lebanon and the role of background and behavioural
determinants. MATERIAL AND METHODS: Oral health was recorded for 652 individuals
(6, 12, 15 and 35 - 44 years old) using the decayed, missing and filled
teeth/decayed and filled teeth (DMFT/dft) index. Data collected was statistically
analysed with statistical significance set at P = 0.05. RESULTS: Overall, mean
DMFT index score was 5.86 (SD 6); composed of 3.64 (SD 4.05) decayed (D) teeth;
1.71 (SD 4.38) missing (M) teeth; 0.87 (SD 2.51) filled (F) teeth. DMFT was
highest in adults (12.71 [SD 7.43]) and had a large component of missing (6.24
[SD 7.02]) and filled (3.31 [SD 4.56]) teeth. DMFT scores ranged between 3.5 (SD
4.44) at 6 years and 4.8 (SD 4.52) at 15 years and the decayed component was the
main contributor. In multivariate analyses, governorate of residence was
statistically significantly (P <= 0.040 and P <= 0.044) associated with D and
DMFT, the degree of disability and caretaker educational level were statistically
significantly (P = 0.009 and P = 0.008) associated with D, oral hygiene practices
were statistically significantly (P <= 0.017; P < 0.001; P <= 0.017; P < 0.001)
associated with D, M, F and DMFT and sugar consumption was statistically
significantly (P <= 0.03 and P <= 0.019) associated with D and DMFT. CONCLUSIONS:
In Lebanon, preventive and treatment programs to improve the oral health status
of institutionalized intellectually disabled subjects are needed.
PMID- 28496965
TI - MALT Lymphoma of Minor Salivary Glands in a Sjogren's Syndrome Patient: a Case
Report and Review of Literature.
AB - BACKGROUND: Sjogren's syndrome is a chronic systemic disease, characterized by
lymphocytic infiltration and destruction mainly of the salivary and lacrimal
glands, resulting in xerostomia and xeropthalmia. Sjogren's syndrome patients
have a 44-fold excess risk for the development of non-Hodgkin's lymphoma
particularly mucosa-associated lymphoid tissue (MALT) lymphoma, prevalently
affecting the major salivary glands. In this report, a rare case of MALT lymphoma
of minor salivary glands in a patient with Sjogren's syndrome is described. A
review of the published cases of MALT lymphoma located in the minor salivary
glands of patients with Sjogren's syndrome is provided. METHODS: In a 64-year-old
female patient previously diagnosed with Sjogren's syndrome, an asymptomatic soft
tissue mass at the palate was noticed, exhibiting rapid enlargement within one
month. With a main differential diagnosis of salivary gland neoplasm or
lymphoproliferative lesion, a partial biopsy was performed accompanied by proper
immunohistochemical analysis. RESULTS: A final diagnosis of MALT lymphoma was
rendered and the patient was referred for further multidisciplinary evaluation.
Gastric endoscopy and biopsy revealed a Helicobacter pylori-negative gastric MALT
lymphoma, while spleen involvement and bone marrow infiltration were also
identified. Patient was classified as having stage IV disseminated disease and a
standard chemotherapy protocol was administered; the treatment was well tolerated
and resulted in complete remission. CONCLUSIONS: This case emphasizes the need
for close monitoring of patients with Sjogren's syndrome by oral medicine
specialists, which, besides ensuring proper management of xerostomia and its
sequelae, may also lead to early recognition of lymphoma development.
PMID- 28496966
TI - Effects of deer on the photosynthetic performance of invasive and native forest
herbs.
AB - Overabundant generalist herbivores can facilitate non-native plant invasions,
presumably through direct and indirect modifications to the environment that
affect plant performance. However, ecophysiological mechanisms behind ungulate
mediated plant invasions have not been well-studied. At a long-term Odocoileus
virginianus (white-tailed deer) exclusion site in a temperate deciduous forest,
we quantified deer-mediated ecophysiological impacts on an invasive biennial
Alliaria petiolata (garlic mustard) and two palatable native herbaceous
perennials, Maianthemum racemosum and Trillium grandiflorum. In mid-summer, we
found that leaf-level light availability was higher in unfenced areas compared
with areas fenced to exclude deer. Alliaria in unfenced areas exhibited 50 %
higher mean maximum photosynthetic rates compared with fenced areas. Further,
specific leaf area decreased by 48 % on average in unfenced areas, suggesting
leaf structural responses to higher light levels. Similarly, Maianthemum had 42 %
higher mean photosynthetic rates and 33 % decreased mean specific leaf area in
unfenced areas, but these functional advantages were likely countered by high
rates of deer herbivory. By contrast, Trillium exhibited significantly lower (26
%) maximum photosynthetic rates in unfenced areas, but SLA did not differ. Deer
mediated differences in light saturated photosynthetic rates for all three
species were only significant during months with overstory tree canopy cover,
when light availability in the herb layer was significantly lower in fenced
areas. Alliaria's enhanced photosynthetic rates implicate overabundant deer, a
situation that is nearly ubiquitous across its invaded range. Collectively, our
results provide empirical evidence that generalist herbivores can alter non
native plant physiology to facilitate invasion.
PMID- 28496967
TI - Synthesis and properties of lysosome-specific photoactivatable probes for live
cell imaging.
AB - Fluorescent dyes have become increasingly important in cell biology since they
enable high signal-to-noise and selectivity in visualizing subcellular
organelles. Photoactivatable dyes allow for tracking and monitoring of a subset
of cells or organelles. Here, we report the synthesis and application of a new
class of large Stokes shift fluorescent dyes that are water-soluble, cell
permeable, non-cytotoxic, and lysosome-specific. Additionally, we demonstrate
temporally controlled sequential photoactivation of individual cells in close
spatial proximity.
PMID- 28496968
TI - Resolving shortages of prescription drugs: the case for public-private
collaboration.
AB - The recent IJHPR article by Schwartzberg and colleagues presents new data on the
growing problem of prescription drug shortages. Resolving shortages typically
involves many participants: government, industry, physicians and healthcare
facilities. Israel has a strong record of informal collaboration that can fix
drug shortages quickly. The success of Israel's informal collaborations, as well
as its formal partnerships, deserves broader recognition at home and more
attention from the international community.
PMID- 28496969
TI - Synthetic approaches to nucleopeptides containing all four nucleobases, and
nucleic acid-binding studies on a mixed-sequence nucleo-oligolysine.
AB - In this article we describe two solid-phase synthetic routes to obtain a nucleo
oligolysine alpha-peptide containing all four natural nucleobases. The first one
is based on the oligomerization of the nucleobase-containing monomers, easily
synthesized as herein described. The second strategy has the advantage of
avoiding the solution synthesis of the monomeric building blocks, leading to the
final nucleopeptide by direct solid-phase couplings of the suitably protected
nucleobases with the free amino groups on the growing peptide chain still
anchored to the resin. Both strategies are general and can be applied to the
synthesis of nucleopeptides having backbones formed by any other diamino acid
moiety decorated with the four nucleobases. We also report the CD and UV studies
on the hybridization properties of the obtained nucleopeptide, containing all
four nucleobases on alternate lysines in the sequence, towards complementary DNA
and RNA strands. The nucleo-oligolysine with a mixed-base sequence did not prove
to bind complementary DNA, but was able to recognize the complementary RNA
forming a complex with a higher melting temperature than that of the
corresponding RNA/RNA natural duplex and comparable with that of the analogous
PNA/RNA system.
PMID- 28496970
TI - Electrical behaviour of native cellulose nanofibril/carbon nanotube hybrid
aerogels under cyclic compression.
AB - Hybrid aerogels consisting of cellulose nanofibers (CNF) and modified few-walled
carbon nanotubes (FWCNT) are investigated under cyclic mechanical compression to
explore "electrical fatigue". For this purpose the FWCNTs were hydrophilized,
thus promoting their aqueous dispersibility to allow FWCNT/CNF hybrid hydrogels,
followed by freeze-drying to obtain hybrid aerogels. The optimized composition
consisting of FWCNT/CNF 20/80 wt/wt showed conductivity of 10-5 S cm-1 as
promoted due to double percolation, and showed only small changes in electrical
and mechanical behaviour upon cycling 100 times. The electrical behaviour under
cycled compression shows good stability and reversibility.
PMID- 28496971
TI - Paramagnetic relaxation enhancement for protein-observed 19F NMR as an enabling
approach for efficient fragment screening.
AB - Protein-observed 19F (PrOF) NMR is an emerging tool for ligand discovery. To
optimize the efficiency of PrOF NMR experiments, paramagnetic relaxation
enhancement through the addition of chelated Ni(II) was used to shorten
longitudinal relaxation time without causing significant line broadening. Thus
enhancing relaxation time leads to shorter experiments without perturbing the
binding of low- or high-affinity ligands. This method allows for time-efficient
screening of potential ligands for a wide variety of proteins in the growing
field of fragment-based ligand discovery.
PMID- 28496972
TI - VUV/UV light inducing accelerated phenol degradation with a low electric input.
AB - This study presents the first evidence for the accelerated degradation of phenol
by Fenton's reagent in a mini-fluidic VUV/UV photoreaction system (MVPS). A low
pressure mercury lamp used in the MVPS led to a complete degradation of phenol
within 4-6 min. The HO and HO2 originating from both Fenton's reagent and VUV
photolysis of water were identified with suitable radical scavengers. The effects
of initial concentrations of phenol, H2O2 and Fe3+ as well as solution pH on
phenol degradation kinetics were examined. Increasing the initial phenol
concentration slowed down the phenol degradation, whereas increasing the initial
H2O2 or Fe3+ concentration accelerated the phenol degradation. The optimal
solution pH was 3.7. At both 254 and 185 nm, increasing phenol concentration
enhanced its absorption for the incident photons. The reaction mechanism for the
degradation of phenol was suggested consistent with the results obtained. This
study indicates that the VUV/UV photo-Fenton process has potential applications
in the treatment of industrial wastewater containing phenol and related aromatic
pollutants.
PMID- 28496973
TI - 8-Styryl-substituted coralyne derivatives as DNA binding fluorescent probes.
AB - Six new 8-styryl-substituted coralyne derivatives 4a-f were synthesized from
coralyne (2) by a base catalysed Knoevenagel type reaction. It was shown by
photometric and fluorimetric titrations of double stranded and quadruplex DNA to
4b-d as well as by fluorimetric DNA denaturation experiments that these ligands
bind to DNA with different binding modes at varying ligand-DNA ratios (LDR).
Specifically, the addition of DNA caused initially a hypochromic effect in
absorbance and, at a particular LDR, the development of a new red shifted
absorption band with a hyperchromic effect. Furthermore, 4b-d induced a
significant and selective stabilization of quadruplex DNA towards unfolding
(DeltaTm = 31.6-32.9 degrees C at LDR = 5), which is even more pronounced as
compared to the parent compound coralyne (2). Most notably, the addition of DNA
to the dimethylamino-substituted derivative 4b leads to a new, strongly red
shifted emission band at 695 nm. Hence, this derivative is a fluorescent probe
that changes its fluorescence colour from green to red in the presence of DNA and
even allows the fluorimetric analysis of living cells by staining of the
nucleoli.
PMID- 28496974
TI - Computational analysis of the solvation of coffee ingredients in aqueous ionic
liquid mixtures.
AB - In this paper, we investigate the solvation of coffee ingredients including
caffeine, gallic acid as representative for phenolic compounds and quercetin as
representative for flavonoids in aqueous mixtures of the ionic liquid 1-ethyl-3
methylimidazolium acetate [C2mim][OAc] at various concentrations. Due to the
anisotropy of the solutes we show that classical Kirkwood-Buff theory is not
appropriate to study solvation effects with increasing ionic liquid content.
However, excess coordination numbers as well as the mean residence time of
solvent molecules at the surface of the solutes can be determined by Voronoi
tessellation. Since the volume of the hydration shells is also available by this
method, solvation free energies will be discussed as a function of the ionic
liquid concentration to yield a physical meaningful picture of solvation for the
anisotropic solutes. Hydrogen bonding capabilities of the solutes and their
relevance for experimental extraction yields from spent coffee grounds are also
discussed.
PMID- 28496975
TI - Convergent synthesis and optical properties of near-infrared emitting
bioluminescent infra-luciferins.
AB - Infra-luciferin, an alkene linked analogue of luciferin, gives bioluminescence
emission >700 nm and has the potential to be used for multiparametric in vivo
imaging. We report here a high yielding, scalable and convergent synthesis of
infra-luciferin which will allow the synthesis of other conjugated luciferins for
investigation in near-infrared bioluminescence imaging. We demonstrated this
potential by using the new route to synthesise a diene linked analogue of
luciferin, the fluorescent and bioluminescent properties of which were compared
to those of d-luciferin and infra-luciferin. We found that extension of
conjugation to a diene linker resulted in the specific bioluminescence activity
being reduced by 3-4 orders of magnitude compared to d-luciferin. Analogous to
its fluorescence emission spectrum, the diene linked analogue exhibited two peaks
in its bioluminescence spectrum, the major one being slightly blue-shifted
compared to natural d-luciferin, and a minor peak at ca. 800 nm. The fluorescence
quantum yield and pH dependence of fluorescence were also determined.
PMID- 28496976
TI - Membrane properties and anti-bacterial/anti-biofouling activity of polysulfone
graphene oxide composite membranes phase inversed in graphene oxide non-solvent.
AB - A new and facile method for the fabrication of polysulfone-graphene oxide
composite membranes is reported, where after casting, phase inversion is carried
out with graphene oxide flakes (GO) in a coagulation bath. The membranes were
characterized and the morphology was analysed using scanning electron microscopy.
A bacterial inhibition ratio of 74.5% was observed with membranes fabricated from
a very low concentration of di-water-GO non-solvent (0.048% of GO). The membranes
were successfully tested for permeate flux and fouling resistance using activated
sludge filtration from an MBR system. The observed trend shows that GO can
operate as a protective barrier for membrane pores against the bacterial
community. To our knowledge this is the first time where the immersion
precipitation mechanism was carried out in a coagulation bath with GO flakes
under continuous stirring. Using this method, a very low concentration of GO is
required to fabricate membranes with conventional GO composite membrane
properties and better selectivity.
PMID- 28496978
TI - Erratum: Evolutionary Medicine: Why do humans get bunions?
AB - [This corrects the article DOI: 10.1093/emph/eox001.].
PMID- 28496977
TI - A generalized quantitative antibody homeostasis model: antigen saturation,
natural antibodies and a quantitative antibody network.
AB - In a pair of articles, we present a generalized quantitative model for the
homeostatic function of clonal humoral immune system. In this second paper, we
describe how antibody production controls the saturation of antigens and the
network of antibody interactions that emerges in the epitome space with the
establishment of the immune system. Efficient control of antigens, be it self or
foreign, requires the maintenance of antibody concentrations that saturate
antigen to relevant levels. Simple calculations suggest that the observed diverse
recognition of antigens by natural antibodies is only possible by cross
reactivity whereby particular clones of antibodies bind to diverse targets and
shared recognition of particular antigens by multiple antibody clones contribute
to the maintenance of antigen control. We also argue that natural antibodies are
none else than the result of thymus-independent responses against immunological
self. We interpret and explain antibody production and function in a virtual
molecular interaction space and as a network of interactions. Indeed, the general
quantitative (GQM) model we propose is in agreement with earlier models, confirms
some assumptions and presumably provides the theoretical basis for the
construction of a real antibody network using the sequence and interaction
database data.
PMID- 28496979
TI - Crystal structure and thermoelectric properties of Sr-Mo substituted CaMnO3: a
combined experimental and computational study.
AB - A combination of experimental and computational techniques has been employed to
study doping effects in perovskite CaMnO3. High quality Sr-Mo co-substituted
CaMnO3 ceramics were prepared by the conventional mixed oxide route.
Crystallographic data from X-ray and electron diffraction showed an orthorhombic
to tetragonal symmetry change on increasing the Sr content, suggesting that Sr
widens the transition temperature in CaMnO3 preventing phase transformation
cracking on cooling after sintering, enabling the fabrication of high density
ceramics. Atomically resolved imaging and analysis showed a random distribution
of Sr in the A-site of the perovskite structure and revealed a boundary structure
of 90 degrees rotational twin boundaries across {101}orthorhombic; the latter
are predominant phonon scattering sources to lower the thermal conductivity as
suggested by molecular dynamics calculations. The effect of doping on the
thermoelectric properties was evaluated. Increasing Sr substitution reduces the
Seebeck coefficient but the power factor remains high due to improved
densification by Sr substitution. Mo doping generates additional charge carriers
due to the presence of Mn3+ in the Mn4+ matrix, reducing electrical resistivity.
The major impact of Sr on thermoelectric behaviour is the reduction of the
thermal conductivity as shown experimentally and by modelling. Strontium
containing ceramics showed thermoelectric figure of merit (ZT) values higher than
0.1 at temperatures above 850 K. Ca0.7Sr0.3Mn0.96Mo0.04O3 ceramics exhibit
enhanced properties with S1000K = -180 MUV K-1, rho1000K = 5 * 10-5 Omegam,
k1000K = 1.8 W m-1 K-1 and ZT ~ 0.11 at 1000 K.
PMID- 28496980
TI - Silver-induced reconstruction of an adeninate-based metal-organic framework for
encapsulation of luminescent adenine-stabilized silver clusters.
AB - Bright luminescent silver-adenine species were successfully stabilized in the
pores of the MOF-69A (zinc biphenyldicarboxylate) metal-organic framework,
starting from the intrinsically blue luminescent bio-MOF-1 (zinc adeninate 4,4'
biphenyldicarboxylate). Bio-MOF-1 is transformed to the MOF-69A framework by
selectively leaching structural adenine linkers from the original framework using
silver nitrate solutions in aqueous ethanol. Simultaneously, bright blue-green
luminescent silver-adenine clusters are formed inside the pores of the
recrystallized MOF-69A matrix in high local concentrations. The structural
transition and concurrent changes in optical properties were characterized using
a range of structural, physicochemical and spectroscopic techniques (steady-state
and time-resolved luminescence, quantum yield determination, fluorescence
microscopy). The presented results open new avenues for exploring the use of MOFs
containing luminescent silver clusters for solid-state lighting and sensor
applications.
PMID- 28496981
TI - Electron injection and scaffold effects in perovskite solar cells.
AB - In spite of the impressive efficiencies reported for perovskite solar cells
(PSCs), key aspects of their working principles, such as electron injection at
the contacts or the suitability of the utilization of a specific scaffold layer,
are not yet fully understood. Increasingly complex scaffolds attained by the
sequential deposition of TiO2 and SiO2 mesoporous layers onto transparent
conducting substrates are used to perform a systematic characterization of both
the injection process at the electron selective contact and the scaffold effect
in PSCs. By forcing multiple electron injection processes at a controlled
sequence of perovskite-TiO2 interfaces before extraction, interfacial injection
effects are magnified and hence characterized in detail. An anomalous injection
behavior is observed, the fingerprint of which is the presence of significant
inductive loops in the impedance spectra with a magnitude that correlates with
the number of interfaces in the scaffold. Analysis of the resistive and
capacitive behavior of the impedance spectra indicates that the scaffolds could
hinder ion migration, with positive consequences such as lowering the
recombination rate and implications for the current-potential curve hysteresis.
Our results suggest that an appropriate balance between these advantageous
effects and the unavoidable charge transport resistive losses introduced by the
scaffolds will help in the optimization of PSC performance.
PMID- 28496982
TI - Blood gases, biochemistry and haematology of Galapagos hawksbill turtles
(Eretmochelys imbricata).
AB - The hawksbill turtle, Eretmochelys imbricata, is a marine chelonian with a circum
global distribution, but the species is critically endangered and has nearly
vanished from the eastern Pacific. Although reference blood parameter intervals
have been published for many chelonian species and populations, including nesting
Atlantic hawksbills, no such baseline biochemical and blood gas values have been
reported for wild Pacific hawksbill turtles. Blood samples were drawn from eight
hawksbill turtles captured in near shore foraging locations within the Galapagos
archipelago over a period of four sequential years; three of these turtles were
recaptured and sampled on multiple occasions. Of the eight sea turtles sampled,
five were immature and of unknown sex, and the other three were females. A
portable blood analyzer was used to obtain near immediate field results for a
suite of blood gas and chemistry parameters. Values affected by temperature were
corrected in two ways: (i) with standard formulas and (ii) with auto-corrections
made by the portable analyzer. A bench top blood chemistry analyzer was used to
measure a series of biochemistry parameters from plasma. Standard laboratory
haematology techniques were employed for red and white blood cell counts and to
determine haematocrit manually, which was compared to the haematocrit values
generated by the portable analyzer. The values reported in this study provide
reference data that may be useful in comparisons among populations and in
detecting changes in health status among Galapagos sea turtles. The findings
might also be helpful in future efforts to demonstrate associations between
specific biochemical parameters and disease or environmental disasters.
PMID- 28496983
TI - Correlated velocity models as a fundamental unit of animal movement: synthesis
and applications.
AB - BACKGROUND: Continuous time movement models resolve many of the problems with
scaling, sampling, and interpretation that affect discrete movement models. They
can, however, be challenging to estimate, have been presented in inconsistent
ways, and are not widely used. METHODS: We review the literature on integrated
Ornstein-Uhlenbeck velocity models and propose four fundamental correlated
velocity movement models (CVM's): random, advective, rotational, and rotational
advective. The models are defined in terms of biologically meaningful speeds and
time scales of autocorrelation. We summarize several approaches to estimating the
models, and apply these tools for the higher order task of behavioral
partitioning via change point analysis. RESULTS: An array of simulation
illustrate the precision and accuracy of the estimation tools. An analysis of a
swimming track of a bowhead whale (Balaena mysticetus) illustrates their
robustness to irregular and sparse sampling and identifies switches between
slower and faster, and directed vs. random movements. An analysis of a short
flight of a lesser kestrel (Falco naumanni) identifies exact moments when
switches occur between loopy, thermal soaring and directed flapping or gliding
flights. CONCLUSIONS: We provide tools to estimate parameters and perform change
point analyses in continuous time movement models as an R package (smoove). These
resources, together with the synthesis, should facilitate the wider application
and development of correlated velocity models among movement ecologists.
PMID- 28496984
TI - Functional conductive nanomaterials via polymerisation in nano-channels: PEDOT in
a MOF.
AB - Reactions inside the pores of metal-organic frameworks (MOFs) offer potential for
controlling polymer structures with regularity to sub-nanometre scales. We report
a wet-chemistry route to poly-3,4-ethylenedioxythiophene (PEDOT)-MOF composites.
After a two-step removal of the MOF template we obtain unique and stable
macroscale structures of this conductive polymer with some nanoscale regularity.
PMID- 28496985
TI - The effects of dietary macronutrient composition on lipid metabolism-associated
factor gene expression in the adipose tissue of chickens are influenced by
fasting and refeeding.
AB - BACKGROUND: Broiler chickens are compulsive feeders that become obese as
juveniles and are thus a unique model for metabolic disorders in humans. However,
little is known about the relationship between dietary composition, fasting and
refeeding and adipose tissue physiology in chicks. Our objective was to determine
how dietary macronutrient composition and fasting and refeeding affect chick
adipose physiology during the early post-hatch period. METHODS: Chicks were fed
one of three isocaloric diets after hatch: high-carbohydrate (HC; control), high
fat (HF; 30% of ME from soybean oil) or high-protein (HP; 25% vs. 22% crude
protein). At 4 days post-hatch, chicks were fed (continuous ad libitum access to
food), fasted (3 h food withdrawal), or refed (fasted for 3 h and refed for 1 h).
Subcutaneous, clavicular, and abdominal adipose tissue was collected for
histological analysis and to measure gene expression, and plasma to measure non
esterified fatty acid (NEFA) concentrations (n = 6-10 per group). RESULTS:
Adipose tissue weights were reduced in chicks that were fed the HP diet and
adipocyte diameter was greater in the adipose tissue of chicks that ate the HF
diet. Consumption of diets differing in protein and fat content also affected
gene expression; mRNAs encoding fatty acid binding protein 4 and a lipolytic
enzyme, monoglyceride lipase, were greater in chicks fed the HC and HF than HP
diet in all three adipose tissue depots. Fasting influenced gene expression in a
depot-dependent manner, where most fasting and refeeding-induced changes were
observed in the clavicular fat of chicks that consumed the HC diet. Fasting
increased plasma NEFA concentrations in chicks fed the HC and HP diets.
CONCLUSIONS: The decreased adipose tissue deposition in chicks fed the HP diet is
likely explained by decreased rates of adipogenesis. Consumption of the HF diet
was associated with greater adipose tissue deposition and larger adipocytes,
likely as a result of greater rates of adipocyte hypertrophy. The depot-dependent
effects of diet and fasting on gene expression may help explain mechanisms
underlying metabolic distinctions among subcutaneous and visceral fat depots in
humans.
PMID- 28496986
TI - A case of stiff dog syndrome associated with anti-glutamic acid decarboxylase
antibodies.
AB - BACKGROUND: The stiff person syndrome (SPS) is a rare and debilitating autoimmune
disorder with an unknown pathogenesis and variable clinical presentation that can
present a diagnostic challenge. Although entities that clinically mimic stiff
person spectrum disorders (SPSD) have manifested in horses, they have not been
reported in dogs. CASE PRESENTATION: We describe a 2-year-old beagle dog
presented for progressive attacks of muscular rigidity and lordosis with
superimposed spasms of the appendicular muscles triggered by tactile stimulation
which resulted in marked gait impairment. Resting electromyography revealed
continuous motor unit activity in the axial musculature. Compared to age-matched
healthy beagle dogs, this patient had elevated glutamic acid decarboxylase
antibody concentrations in serum and cerebrospinal fluid. CONCLUSION: This dog
presented with phenotypic, electrodiagnostic, and immunologic criterion
consistent with an SPSD, including elevated anti-GAD antibody titers, which we
have termed the "stiff dog syndrome (SDS)". Durable clinical improvement was
achieved with symptomatic and immunosuppressive treatments including baclofen,
gabapentin, prednisone, and intravenous immunoglobulin.
PMID- 28496987
TI - Effect of health foods on cytochrome P450-mediated drug metabolism.
AB - BACKGROUND: Health foods have been widely sold and consumed in Japan. There has
been an increase in reports of adverse effects in association with the expanding
health food market. While health food-drug interactions are a particular concern
from the viewpoint of safe and effective use of health foods, information
regarding such interactions is limited owing to the lack of established methods
to assess the effects of health food products on drug metabolism. We therefore
developed cells that mimicked the activities of cytochrome P450 1A2 (CYP1A2),
CYP2C9, CYP2C19, CYP2D6, and CYP3A4, which strongly contribute to drug metabolism
in human hepatocytes, and established a system to assess the inhibitory activity
of health foods toward P450-mediated metabolism. METHODS: We simultaneously
infected HepG2 cells with five P450-expressing adenoviruses (Ad-CYP1A2, Ad
CYP2C9, Ad-CYP2C19, Ad-CYP2D6, and Ad-CYP3A4) to mimic the activity levels of
these P450s in human hepatocytes, and named them Ad-P450 cells. The activity
levels of P450s in Ad-P450 cells and human hepatocytes were calculated via
simultaneous liquid chromatography/tandem mass spectrometry analysis utilizing a
P450 substrate cocktail. RESULTS: We established Ad-P450 cells mimicking the
activity levels of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 in human
hepatocytes. We determined the Km values of P450 substrates and IC50 values of
P450 inhibitors in Ad-P450 cells. These values were approximately equivalent to
those obtained in previous studies. We investigated the inhibitory effects of 172
health foods that were recently in circulation in Japan on P450-mediated
metabolism using Ad-P450 cells. Of the 172 health foods, five products (two
products having dietary effects, one turmeric-based product, one collagen-based
product, and one propolis-containing product) simultaneously inhibited the five
P450s by more than 50%. Another 29 products were also confirmed to inhibit one or
more P450s. CONCLUSIONS: We established a comprehensive assessment system to
elucidate the effects of health foods on P450-mediated metabolism and identified
the inhibitory activity of 34 of 172 health foods toward the drug-metabolizing
P450s. Our results may provide useful information to predict health food-drug
interactions.
PMID- 28496989
TI - Correction.
AB - [This corrects the article on p. 349 in vol. 40.].
PMID- 28496988
TI - Randomised controlled field study to evaluate the efficacy and clinical safety of
a single 8 mg/kg injectable dose of marbofloxacin compared with one or two doses
of 7.5 mg/kg injectable enrofloxacin for the treatment of Actinobacillus
pleuropneumoniae infections in growing-fattening pigs in Europe.
AB - BACKGROUND: Acute outbreaks of Actinobacillus pleuropneumoniae (APP) require
rapid, effective, parenteral antimicrobial treatment. The efficacy and safety of
a single, short-acting, high dose of marbofloxacin (Forcyl(r) swine 160 mg/mL)
compared with 1 or 2 doses of 7.5 mg/kg enrofloxacin in APP outbreaks in European
farms was studied. METHODS: A controlled, randomised block, blinded, multicentre,
field study was conducted on four farms with acute respiratory disease associated
with APP. Animals with clinical signs of respiratory disease were allocated
similarly to intramuscular treatments of either a single dose 8 mg/kg
marbofloxacin on day 0 or, 7.5 mg/kg enrofloxacin (Baytril 1nject(r)) on day 0
and again on day 2, if clinical signs had not improved. RESULTS: The results were
similar for intention to treat (242 pigs) and per protocol populations (239
pigs). On day 0, all pigs had pyrexia (means, 40.6 degrees C), moderate to
severe clinical signs (depression, cough, dyspnoea). Following treatment, animals
improved rapidly and on day 7, clinical signs were absent or mild in all pigs and
mean temperatures for each treatment were <39.5 degrees C (P > 0.05). The
primary efficacy criterion, animals cured, for marbofloxacin and enrofloxacin was
81.8 and 81.4% on day 7, and 84.2 and 82.2% on day 21, respectively. Results for
cure, respiratory disease removals and mortalities, and relapses were compared
using confidence intervals and confirmed that marbofloxacin was non-inferior to
enrofloxacin (P > 0.05). There were no significant treatment differences in live
weight gains, adverse events and injection site reactions (<2.5% animals) (P >
0.05). Significantly more animals developed concurrent disorders in the
enrofloxacin (7.5%) than marbofloxacin (0.0%) group (P < 0.01). On day 0, the
MIC90 values of APP for marbofloxacin and enrofloxacin were 0.06 MUg/mL for APP,
less than the clinical breakpoints. CONCLUSIONS: Marbofloxacin (single dose of 8
mg/kg) and enrofloxacin (1 or 2 doses of 7.5 mg/kg) were clinically safe and
effective in the treatment of clinical respiratory disease associated
predominantly with APP in four European commercial, fattening pig herds.
PMID- 28496991
TI - TORC1 coordinates the conversion of Sic1 from a target to an inhibitor of cyclin
CDK-Cks1.
AB - Eukaryotic cell cycle progression through G1-S is driven by hormonal and growth
related signals that are transmitted by the target of rapamycin complex 1 (TORC1)
pathway. In yeast, inactivation of TORC1 restricts G1-S transition due to the
rapid clearance of G1 cyclins (Cln) and the stabilization of the B-type cyclin
(Clb) cyclin-dependent kinase (CDK) inhibitor Sic1. The latter mechanism remains
mysterious but requires the phosphorylation of Sic1-Thr173 by Mpk1 and
inactivation of the Sic1-pThr173-targeting phosphatase (PP2ACdc55) through
greatwall kinase-activated endosulfines. Here we show that the Sic1-pThr173
residue serves as a specific docking site for the CDK phospho-acceptor subunit
Cks1 that sequesters, together with a C-terminal Clb5-binding motif in Sic1, Clb5
CDK-Cks1 complexes, thereby preventing them from flagging Sic1 for ubiquitin
dependent proteolysis. Interestingly, this functional switch of Sic1 from a
target to an inhibitor of cyclin-CDK-Cks1 also operates in proliferating cells
and is coordinated by the greatwall kinase, which responds to both Cln-CDK
dependent cell-cycle and TORC1-mediated nutritional cues.
PMID- 28496990
TI - mTORC1 regulates mannose-6-phosphate receptor transport and T-cell vulnerability
to regulatory T cells by controlling kinesin KIF13A.
AB - Mannose-6-phosphate receptor (M6PR) that facilitates cellular uptake of M6P
bearing proteins, including serine-protease granzyme-B (Gzm-B) has an important
role in T-cell activation, migration and contraction. However, molecular
mechanisms controlling M6PR expression in T cells remain poorly understood. Here,
we show that M6PR expression on T cells is distinctively controlled by two common
gamma-chain cytokines interleukin-2 (IL-2) and IL-7, and the differential M6PR
expression is not caused by an altered synthesis of M6PR protein, but is a result
of distinct regulation of kinesin-3 motor-protein KIF13A that transport M6PR onto
cell surfaces. Using signaling pathway-specific inhibitors, we determine that IL
2 and IL-7 distinctly regulate KIF13A and beta1-adaptin and cell-surface M6PR by
controlling a kinase mammalian target of rapamycin complex-1 (mTORC1).
Inflammatory cytokine IL-2 and prosurvival cytokine IL-7 induce strong and weak
activation of mTORC1, leading to up- and downregulation of motor-protein KIF13A
and KIF13A-motorized M6PR on T cells, and formation of IL-2 and IL-7 effectors
with M6PRhigh and M6PRlow cell-surface expression, respectively. Inhibition of
mTORC1 by rapamycin reduces T-cell expression of KIF13A and cell-surface M6PR,
and increases T-cell survival in Listeria monocytogenes-infected mice. Using
regulatory T (Treg)-cell-enriched mouse tumor model, we determine that M6PRhigh
IL-2 effectors but not M6PRlow IL-7 effectors adoptively transferred into tumors
are vulnerable to Treg Gzm-B-mediated cell apoptosis. Inhibition of mTORC1 or
small interfering RNA-mediated knockdown of KIF13A or M6PR renders IL-2 effectors
refractory to Treg Gzm-B lethal hit. Overall, our data offer novel mechanistic
insights into T-cell M6PR regulation, and Treg-resistant/Treg-susceptible
phenomenon. Furthermore, regulation of T-cell fate vis-a-vis Treg suppression via
the mTORC1-KIF13A-M6PR axis provides a proof of concept for therapeutic
strategies to target cancer, infectious and autoimmune diseases.
PMID- 28496992
TI - Flavored little cigar smoke induces cytotoxicity and apoptosis in airway
epithelia.
AB - Addition of flavors reduces the harsh taste of tobacco, facilitating the
initiation and maintenance of addiction among youths. Flavored cigarettes (except
menthol) are now banned. However, the legislation on little cigars remains
unclear and flavored little cigars are currently available for purchase. Since
inhaled tobacco smoke directly exerts toxic effects on the lungs, we tested
whether non-flavored and flavored little cigar smoke exposure had the potential
for harm in cultured pulmonary epithelia. We cultured Calu-3 lung epithelia on
both 96-well plates and at the air-liquid interface and exposed them to smoke
from non-flavored Swisher Sweets and flavored (sweet cherry, grape, menthol,
peach and strawberry) Swisher Sweets little cigars. Irrespective of flavor, acute
little cigar smoke exposure (10*35 ml puffs) significantly increased cell death
and decreased the percentage of live cells. Chronic exposure (10*35 ml puffs per
day for 4 days) of smoke to Calu-3 cultures significantly increased lactate
dehydrogenase release, further indicating toxicity. To determine whether this
exposure was associated with increased cell death/apoptosis, a protein array was
used. Chronic exposure to smoke from all types of little cigars induced the
activation of the two major apoptosis pathways, namely the intrinsic
(mitochondrial-mediated) and the extrinsic (death receptor-mediated) pathways.
Both flavored and non-flavored little cigar smoke caused similar levels of
toxicity and activation of apoptosis, suggesting that flavored and non-flavored
little cigars are equally harmful. Hence, the manufacture, advertisement, sale
and use of both non-flavored and flavored little cigars should be strictly
controlled.
PMID- 28496993
TI - Successful Application of Whole Genome Sequencing in a Medical Genetics Clinic.
AB - A pilot program was initiated using whole genome sequencing (WGS) to diagnose
suspected genetic disorders in the Genetics Clinic at Children's Hospital of
Wisconsin. Twenty-two patients underwent WGS between 2010 and 2013. Initially, we
obtained a 14% (3/22) diagnosis rate over 2 years; with subsequent reanalysis,
this increased to 36% (8/22). Disease causing variants were identified in SKIV2L,
CECR1, DGKE, PYCR2, RYR1, PDGFRB, EFTUD2, and BCS1L. In 75% (6/8) of diagnosed
cases, the diagnosis affected treatment and/or medical surveillance.
Additionally, one case demonstrated a homozygous A18V variant in VLDLR that
appears to be associated with a previously undescribed phenotype.
PMID- 28496994
TI - Novel Causative Variants in DYRK1A, KARS, and KAT6A Associated with Intellectual
Disability and Additional Phenotypic Features.
AB - Patients with unclear patterns of developmental and cognitive delay may go years
without a definitive diagnosis despite extensive testing due to overlapping
phenotypes of many genetic disorders. In this study, we identified causative
variants in DYRK1A, KARS, or KAT6A in four individuals with global developmental
delay and various findings including microcephaly and sensorineural hearing loss
using whole exome sequencing. We present the cognitive, neurologic, and physical
findings of four individuals to expand the clinical knowledge of possible
features of the phenotypes of three rare genetic disorders. Through this process,
we provide support for the use of whole exome sequencing in the setting of
severe, intellectual disability or in those in whom a genetic disorder is
suspected despite initial negative testing.
PMID- 28496995
TI - Genomic Microarray in Intellectual Disability: The Usefulness of Existing Systems
in the Interpretation of Copy Number Variation.
AB - Whole genome array technology is an essential tool for the detection of a large
number of copy number variants (CNVs) in patients with ID and/or multiple
congenital anomalies. However, the clinical significance of some microimbalances
is not known. In this article, we succeeded to detect seven new variations of
unknown significance (dup12p13.33, dup2p16.3, dupXq13.2, del12q24.33,
dup16p13.11, trip4q22.1, and dup9p21.3), one CNV classified as known pathogenic
syndrome (del22q13.31-q33), and one CNV classified as potentially pathogenic
(del11q24.3). We emphasize the role of comparative genomic hybridization arrays
in the investigation of intellectual disability and evaluate the usefulness of
existing systems in the interpretation of CNVs.
PMID- 28496996
TI - Anterior Abdominal Wall Defects, Diaphragmatic Hernia, and Other Major Congenital
Malformations of the Musculoskeletal System in Barbados, 1993-2012.
AB - This study describes the prevalence and patterns of major congenital
malformations of the musculoskeletal system and the resulting morbidity and
mortality. It is a retrospective population-based study over the period 1993 to
2012. The overall prevalence of major congenital malformations of the
musculoskeletal system was 9.02/10,000 live births. The prevalences of
omphalocele, gastroschisis, and diaphragmatic hernia were 2.53, 2.22, and 1.42
per 10,000 live births, respectively. The case fatality ratio for the
omphalocele, gastroschisis, and diaphragmatic hernia was 12.5, 28.5, and 67%,
respectively. In conclusion, the prevalence rate of the major congenital
malformations of the musculoskeletal system was higher than those reported in
retrospective studies from other countries and remained static during the study
period. These defects were associated with a high mortality rate and contributed
significantly to the overall neonatal mortality in this country.
PMID- 28496997
TI - A New Split Hand/Foot Malformation with Long Bone Deficiency Familial Case.
AB - Split hand/foot malformation with long bone deficiency (SHFLD) is a congenital
limb anomaly where hands and/or feet cleft and syndactyly are associated with
long bone defects, usually involving the tibia. Previously published data
reported that 17p13.3 chromosomal duplication, including the BHLHA9 gene, has
been associated with the distinct entity, termed SHFLD3 (OMIM 612576), inherited
as an autosomal dominant trait. Here, we present a family with three members
affected by SHFLD harboring BHLHA9 duplication. We exploited in vitro
differentiation system to promote proband's skin fibroblasts toward osteoblastic
lineage, and we observed a slight but consistent delay in the mineralization
pattern. This result possibly suggests an impairment of the osteogenic process in
the affected members.
PMID- 28496998
TI - Multisystem Involvement in a Patient with a PTCH1 Mutation: Clinical and Imaging
Findings.
AB - In this article, we report on a Brazilian female patient born to consanguineous
parents and presenting with alobar holoprosencephaly, severe eye involvement, and
unusual skin hyperpigmented lesions. She was found to have a mutation (c.2240T >
C; p.Val751Gly) in exon 15 of the PTCH1 gene. Mutations in this gene are
associated with the nevoid basal cell carcinoma syndrome (NBCCS, OMIM 109400)
and, in other instances, with holoprosencephaly (holoprosencephaly-7, OMIM
610828). Severe eye involvement ranging from orbital coloboma to microphthalmia
has been seldom reported in patients with NBCCS with PTCH1 mutations. To our
knowledge, this is the first report of an individual with central nervous system,
skin, and eye manifestations due to a PTCH1 mutation. Mechanisms involved in
these multisystem manifestations are discussed.
PMID- 28496999
TI - The Clinical Manifestations and Genetic Implications of Baraitser-Winter Syndrome
Type 2.
AB - An 18-year-old Caucasian male was born by cesarean section weighing 2.6 kg (5 lb
14 oz) at birth after an uncomplicated pregnancy with no perinatal complications.
Around 4 to 5 months of age, the patient's mother initially became concerned as
he was experiencing signs of developmental delay and a mild floppy tone, in
addition to facial features that resembled some form of mental retardation. The
patient's older brother also experienced similar developmental symptoms and
facial features that presented around the same age period as our patient. It was
initially thought to be Down syndrome; however, both the patient and his brother
tested negative for Down syndrome on chromosomal analyses. There was also a
question of whether the patient had some form of autism spectrum disorder, but
doctors were unable to specifically confirm this. Now at the age of 18 years, the
patient has no understandable speech with distinctive facial features such as a
broad nasal bridge and prominent epicanthic folds, lissencephaly, smaller than
average head size, intellectual disability, and hearing loss. It was discovered,
through trio-based exome sequencing, that the patient had a de novo missense
mutation (p.Ser155Phe) in the ACTG1 gene, which has been linked to the rare
syndrome known as Baraister-Winter syndrome type 2. Baraitser-Winter syndrome 2
is a unique variant that is clinically similar to Baraitser-Winter syndrome type
1; however, only seven previous cases have been reported.
PMID- 28497000
TI - What Is the Teratogenic Risk of Mycophenolate?
AB - Mycophenolate is often used in the management of systemic lupus erythematosus. It
has often been associated with significant fetal embryopathy, including fetal
loss and multiple anomalies. The Food and Drug Administration has directed that
women should be counseled regarding this prior to initiating treatment with this
drug. Isolated total anomalous pulmonary venous return (TAPVR) is a rare
association seen with its use in pregnancy.
PMID- 28497001
TI - Klinefelter Syndrome in Association with Tetralogy of Fallot and Congenital
Diaphragmatic Hernia.
AB - Klinefelter syndrome (KS) is the most common sex chromosomal aneuploidy in males.
Major cardiovascular and diaphragmatic anomalies are uncommon in this syndrome.
Here we report an infant with KS who had tetralogy of Fallot and congenital
diaphragmatic hernia, all of which were identified prenatally and managed
successfully after birth. Microarray analysis did not reveal any deletions or
duplications other than the additional X-chromosome, to account for the
additional abnormalities in this infant. To the authors' knowledge, this is the
first such report of major cardiac and diaphragm anomaly occurring together, in
an infant with KS.
PMID- 28497002
TI - Overlap between Fibular Aplasia, Tibial Campomelia, and Oligosyndactyly and
Fuhrmann's Syndromes in an Egyptian Female Infant.
AB - We report a rare congenital limb defect with combined features of both fibular
aplasia, tibial campomelia, and oligosyndactyly (FATCO) and Fuhrmann's syndromes.
A female newborn infant, born to nonconsanguineous Egyptian parents, presented
with isolated abnormalities of the lower limbs comprising bilateral shortening
and anterior bowing of the lower limbs at the distal third of the tibia and split
foot. Radiographic examination revealed complete absence of both fibulae,
anterolateral bowing and shortening of the tibia, bowing of the femora, and
absence of several metatarsal and phalangeal bones. The upper limbs were
clinically and radiologically normal, and the infant had neither facial
dysmorphism nor other associated visceral anomalies. The presented case
highlights an extremely rare limb deficiency syndrome, and together with
additional case reports, it could be useful to further delineate this condition.
PMID- 28497003
TI - Achondroplasia and Biliary Atresia: A Rare Association and Review of Literature.
AB - Achondroplasia (ACH) occurs in most cases as de novo mutations of the gene
encoding fibroblast growth factor receptor 3 (FGFR3). Biliary atresia (BA) is a
progressive neonatal inflammatory and fibro-obliterative cholangiopathy affecting
the extra- and intrahepatic biliary tree to varying degrees, and it results in
obstruction to bile flow and cholestatic jaundice in neonates. BA is thought to
be a multifactorial disease, genome association studies have shown abnormalities
in susceptibility genes, and levels of fibroblast growth factor 21 (FGF21) and
fibroblast growth factor 23 (FGF23) have been noted to be increased. These two
conditions occurring in the same patient has never been reported before.
PMID- 28497004
TI - Progressive Familial Intrahepatic Cholestasis Type 2 in an Indian Child.
AB - Progressive familial intrahepatic cholestasis (PFIC) is a chronic cholestasis
syndrome that begins in infancy and usually progresses to cirrhosis within the
first decade of life. There are three varieties of PFIC described: PFIC-1 occurs
due to mutations in the ATP8B1 gene mapped to 18q21.31, PFIC-2 due to mutations
in ABCB11 mapped to 2q24, and PFIC-3 due to mutations in ABCB4 located on
7q21.12. We report an Indian child whose mutation analysis was suggestive of PFIC
2. He underwent a biliary diversion at 31/2 years of age but subsequently died
secondary to massive hematemesis.
PMID- 28497006
TI - Under Pressure: Intraluminal Filling Pressures of Postpartum Hemorrhage Tamponade
Balloons.
AB - Objective Uterine tamponade by fluid-filled balloons is now an accepted method of
controlling postpartum hemorrhage. Available tamponade balloons vary in design
and material, which affects the filling attributes and volume at which they
rupture. We aimed to characterize the filling capacity and pressure-volume
relationship of various tamponade balloons. Study Design Balloons were filled
with water ex vivo. Intraluminal pressure was measured incrementally (every 10 mL
for the Foley balloons and every 50 mL for all other balloons). Balloons were
filled until they ruptured or until 5,000 mL was reached. Results The Foley
balloons had higher intraluminal pressures than the larger-volume balloons. The
intraluminal pressure of the Sengstaken-Blakemore tube (gastric balloon) was
initially high, but it decreased until shortly before rupture occurred. The Bakri
intraluminal pressure steadily increased until rupture occurred at 2,850 mL. The
condom catheter, BT-Cath, and ebb all had low intraluminal pressures. Both the BT
Cath and the ebb remained unruptured at 5,000 mL. Conclusion In the setting of
acute hemorrhage, expeditious management is critical. Balloons that have a low
intraluminal pressure-volume ratio may fill more rapidly, more easily, and to
greater volumes. We found that the BT-Cath, the ebb, and the condom catheter all
had low intraluminal pressures throughout filling.
PMID- 28497007
TI - Accuracy of Blood Loss Measurement during Cesarean Delivery.
AB - Objective This study aims to compare the accuracy of visual, quantitative
gravimetric, and colorimetric methods used to determine blood loss during
cesarean delivery procedures employing a hemoglobin extraction assay as the
reference standard. Study Design In 50 patients having cesarean deliveries blood
loss determined by assays of hemoglobin content on surgical sponges and in
suction canisters was compared with obstetricians' visual estimates, a
quantitative gravimetric method, and the blood loss determined by a novel
colorimetric system. Agreement between the reference assay and other measures was
evaluated by the Bland-Altman method. Results Compared with the blood loss
measured by the reference assay (470 +/- 296 mL), the colorimetric system (572 +/
334 mL) was more accurate than either visual estimation (928 +/- 261 mL) or
gravimetric measurement (822 +/- 489 mL). The correlation between the assay
method and the colorimetric system was more predictive (standardized coefficient
= 0.951, adjusted R2 = 0.902) than either visual estimation (standardized
coefficient = 0.700, adjusted R2 = 00.479) or the gravimetric determination
(standardized coefficient = 0.564, adjusted R2 = 0.304). Conclusion During
cesarean delivery, measuring blood loss using colorimetric image analysis is
superior to visual estimation and a gravimetric method. Implementation of
colorimetric analysis may enhance the ability of management protocols to improve
clinical outcomes.
PMID- 28497005
TI - The Transcription Regulator Kruppel-Like Factor 4 and Its Dual Roles of Oncogene
in Glioblastoma and Tumor Suppressor in Neuroblastoma.
AB - The Kruppel-like factor 4 (KLF4) gene is located on chromosome 9q31. All of the
currently known 17 KLF transcription regulators that have similarity with members
of the specificity protein family are distinctly characterized by the Cys2/His2
zinc finger motifs at their carboxyl terminals for preferential binding to the
GC/GT box or the CACCC element of the gene promoter and enhancer regions. KLF4 is
a transcriptional regulator of cell proliferation, differentiation, apoptosis,
migration, and invasion, emphasizing its importance in diagnosis and prognosis of
particular tumors. KLF4 has been implicated in tumor progression as well as in
tumor suppression, depending on tumor types and contexts. Different studies so
far strongly suggest that KLF4 acts as an oncogene in glioblastoma, which is the
most malignant and prevalent brain tumor in human adult. It is now well
established that the presence of glioblastoma stem cells (GSCs) in glioblastoma
causes therapy resistance and progressive growth of the tumor. Because KLF4 is
one of the key stemness factors in GSCs, it is likely that KLF4 contributes
significantly to the survival of GSCs and the recurrence of glioblastoma. On the
other hand, recent studies show that KLF4 can act as a tumor suppressor in human
malignant neuroblastoma, which is a deadly tumor mostly in children, by
inhibiting the cell cycle and activating the cell differentiation and death
pathways. Our increasing understanding of the molecular mechanisms of the
contrasting roles of KLF4 in glioblastoma and neuroblastoma is useful for
superior diagnosis, therapy, and prognosis of these tumors of the nervous system.
PMID- 28497008
TI - THE POSITIVITY OFFSET THEORY OF ANHEDONIA IN SCHIZOPHRENIA.
AB - Prior studies have concluded that schizophrenia patients are not anhedonic
because they do not report reduced experience of positive emotion to pleasant
stimuli. The current study challenged this view by applying quantitative methods
validated in the Evaluative Space Model of emotional experience to test the
hypothesis that schizophrenia patients evidence a reduction in the normative
"positivity offset" (i.e., the tendency to experience higher levels of positive
than negative emotional output when stimulus input is absent or weak).
Participants included 76 schizophrenia patients and 60 healthy controls who
completed an emotional experience task that required reporting the level of
positive emotion, negative emotion, and arousal to photographs. Results indicated
that although schizophrenia patients evidenced intact capacity to experience
positive emotion at high levels of stimulus input, they displayed a diminished
positivity offset. Reductions in the positivity offset may underlie volitional
disturbance, limiting approach behaviors toward novel stimuli in neutral
environments.
PMID- 28497009
TI - False Positive Positron Emission Tomography / Computed Tomography Scans in
Treated Head and Neck Cancers.
AB - OBJECTIVE: Positron emission tomography/computed tomography (PET/CT) imaging for
head and neck cancers (HNC) is commonly utilized for post-treatment assessment.
Though PET/CT in this setting has been reported to have high negative predictive
values (> 90%), positive predictive values have been reported at approximately
50%, leading to high rates of false positivity (FP) and troubling management
decisions for both patient and practitioner. The objective of this study was to
identify patient, disease, treatment and imaging factors that might be associated
with a higher likelihood of FP on initial post-treatment PET/CT imaging for
patients treated for HNC. MATERIALS AND METHODS: A retrospective chart review was
performed on 84 patients treated for HNC who received radiation therapy (RT) as
part of their overall management from October 2005 to August 2013. Of the
patients screened, 19 were found to have mucosally based squamous cell carcinoma
(SCC) with positive initial post-treatment PET/CT studies (23%). Fisher's exact
test was used to analyze the association between categorical variables and FP,
including patient's gender, disease laterality, primary tumor site and stage,
nodal and overall stage, high dose RT fraction size, number of RT fractions
completed, total RT dose, biologically effective dose and timing of PET/CT
acquisition. Wilcoxon rank-sum test was used to analyze the association between
continuous variables and FP, including patient age, total elapsed days of RT, an
amount of infused fluorodeoxyglucose 18F-FDG, pre-PET/CT serum glucose levels,
and maximum standardized uptake value SUVmax. Statistically significant findings
were those that were deemed p <0.05. RESULTS: Among patients with positive
initial post-treatment PET/CT scans for treated HNC, there was a lower proportion
of higher primary disease stage associated with FP versus true positivity (T
stage 3-4: 20 vs 78%, respectively, p=0.023). We also discovered that 50% of
patients that underwent confirmation for FP findings suffered serious
complications as a direct consequence of invasive exploratory procedures.
CONCLUSIONS: Although PET/CT is known for its exceptional negative predictive
value (> 90%) in the post-treatment setting for HNC, high rates of FP remains a
clinical challenge. Our study suggests that tumor stage (T-stage) may impact FP
rates in positive initial post-treatment PET/CT scans. We recommend careful
multidisciplinary discussion regarding positive PET/CT studies in the post
treatment setting for HNC, particularly if invasive intervention is considered.
PMID- 28497010
TI - A Review of the Value of Procalcitonin as a Marker of Infection.
AB - Septicemia is a growing problem within the United States (US), which increases
mortality and the cost of care. Procalcitonin is a pro-inflammatory marker that
could be useful in the diagnosis of infection. In the past, procalcitonin levels
have been evaluated to diagnose sepsis or guide antibiotic therapy, but it was
not determined if it would differentiate between sepsis and other causes of
inflammation. Studies reviewed here showed procalcitonin to be a useful biomarker
as an indication of bacterial infection. Infections can be diagnosed earlier and
managed appropriately to avoid progression to septicemia, reduce mortality, and
overall medical costs.
PMID- 28497011
TI - Reference Data for Standardized Quality of Life Questionnaires in Indian Patients
with Brain Metastases from Non-small Cell Lung Cancer: Results from a Prospective
Study.
AB - INTRODUCTION: Reference data for European Organization for Research and Treatment
of Cancer (EORTC) quality of life questionnaires do not include studies from the
Indian subcontinent. The objective of the current study was to establish a
reference dataset for Indian patients of non-small cell lung cancer (NSCLC)
presenting with brain metastases (BM). MATERIAL AND METHODS: One hundred forty
patients with NSCLC with BM treated between 2012-2015 were registered in a
prospective cohort study (CTRI/2013/01/003299). The baseline quality of life was
evaluated using the EORTC general quality of life questionnaire QLQ-C30 and lung
cancer specific module LC13. Minimum important difference (MID) scores for
individual domains of the EORTC QLQ-C30 and LC13 questionnaires were derived (MID
= 0.2 x standard deviation) from the reference data for patients with
recurrent/metastatic lung cancers. In addition, a systematic review was conducted
to identify studies reporting baseline quality of life scores for
recurrent/metastatic NSCLC. RESULTS: Scores of several functional as well as
symptom scales in the current NSCLC population differed by more than the MID from
the baseline mean scores in the reference EORTC population as well as that
reported from other studies. Differences in mean score from the EORTC reference
data ranged from 6.2 and 9.4 points for the role functioning and cognitive
functioning domains. In the symptom scales, the largest differences were observed
for the financial difficulties (23.9) scores for the QLQ-C30 and peripheral
neuropathy (21.7) for LC13 questionnaires. CONCLUSION: The current study
demonstrates that baseline reference scores need to be established for patients
from the Indian subcontinent. The findings from the current study have important
implications for studies employing quality of life (QOL) assessment in the Indian
NSCLC patient population.
PMID- 28497012
TI - Electrocatalytic Oxidation of Alcohols, Tripropylamine, and DNA with Ligand-Free
Gold Nanoclusters on Nitrided Carbon.
AB - Electrocatalytic properties of ligand-free gold nanoclusters (AuNCs, <2 nm) grown
on nitrided carbon supports (denoted as AuNCs@N-C) were evaluated for the
oxidation of representative organic molecules including alcohols, an amine, and
deoxyguanosine in oligonucleotides. AuNCs@N-C catalysts were incorporated into
films of architecture {PDDA/AuNCs@N-C} n by using layer-by-layer assembly with
oppositely charged poly(diallyldimethylammonium) (PDDA) on pyrolytic graphite
(PG) electrodes. Cyclic voltammetry and electrochemical impedance spectroscopy
(EIS) were used to survey the electrocatalytic properties of these AuNCs@N-C
films. Ligand-free AuNCs in these films demonstrated excellent electrocatalytic
oxidation activity with maximum peak currents and the lowest potentials for
oxidizing ethanol, propanol, and tripropylamine (TprA) compared to controls with
Au-surface capping agents or to larger sized Au nanocrystals on the nitrided
carbon supports. EIS kinetic studies showed that ligand-free AuNCs films have the
smallest charge-transfer resistance, largest electrochemically active surface
area, and largest apparent standard rate constants, as compared to the control
films for all compounds examined. DNA films on AuNCs@N-C were oxidized at
deoxyguanosine moieties with good catalytic activity that depended on charge
transport within the films.
PMID- 28497015
TI - Aesthetic breast surgery, scientific approach.
PMID- 28497014
TI - The E. histolytica Genome Structure and Virulence.
AB - The outcome of an Entamoeba histolytica infection is variable and the
contribution of genetic diversity within E. histolytica to human disease is not
fully understood. The information provided by the whole genome sequence of the E.
histolytica reference laboratory strain (HM-1:IMSS) and thirteen additional
laboratory strains have been made publically available. In this review theories
on the source of the unexpected level of structural diversity found in E.
histolytica will be discussed.
PMID- 28497013
TI - Racial/ethnic disparities in environmental endocrine disrupting chemicals and
women's reproductive health outcomes: epidemiological examples across the life
course.
AB - Disparities in women's reproductive health outcomes across the life course have
been well-documented. Endocrine disrupting chemicals may be one factor driving
disparities, as studies suggest exposure to certain environmental endocrine
disrupting chemicals, such as certain phthalates, bisphenol A, parabens and
polybrominated diphenyl ethers are higher in non-whites. Yet, a limited amount of
research has focused on these chemical exposures as a potential mediator of
racial/ethnic differences in women's reproductive health outcomes, such as
pubertal development, fibroids, infertility, and pregnancy complications. Given
that race/ethnicity is a social construct, the purpose of this review was to
present the current state of the literature on racial/ethnic disparities in both
environmental endocrine disrupting chemicals, as well as associations between
these chemicals and selected women's reproductive health outcomes. Our goal was
to evaluate literature from populations based in the United States to: 1)
characterize racial/ethnic differences in environmental endocrine disrupting
chemicals and 2) systematically review literature on environmental endocrine
disrupting chemicals and selected women's health outcomes in populations
containing more than one racial/ethnic group. This review highlights the need for
future work in determining whether higher exposures to some environmental
endocrine disrupting chemicals might partly explain differences in women's
reproductive health outcomes in these higher-exposure and high-risk groups.
PMID- 28497016
TI - Small refinements in breast reconstruction: a technique for inframammary fold
creation.
AB - BACKGROUND: In breast reconstructive surgery, the inframammary fold (IMF) is an
essential component of breast identity. The lack of the IMF following previous
mastectomy requires restoration. We have developed a new IMF reconstruction
technique using the posterior sheet (PS) of the expander capsule. This article
presents our 10-year experience of performing this original technique during two
stage breast reconstruction. METHODS: Preoperatively, the midline, lateral, and
medial borders (MBs) of the implant pocket and the new IMF line were marked.
After extracting the expander, the anterior sheet of the expander capsule was
removed with the exception of its lowest 2-cm portion. Two needles were placed at
the intersection of the new IMF line with the lateral border (LB) of the implant
pocket and its MB. Within the pocket, horizontal dissection of the PS of the
capsule was performed from one needle to another, after which the sheet was
mobilized downward. The mobilized free border of the PS was pulled upward until
the inframammary crease was at the new marked location, and then fixed with non
absorbable interrupted sutures to the underlying tissues. An implant was placed
over this layer. The covering tissues were then closed. RESULTS: A total of 321
patients were included. The median age was 38 years (range, 18-58 years). No
serious wound complications were observed. Breast-thoracic angle decreased in 21
patients (6.5%), and the distance from the IMF to the lower border of breast
segment III was greater than that of the contralateral breast in 14 patients
(4.4%). CONCLUSION: This technique provides a well-defined IMF without
indentations or retraction. The results are stable on long-term follow-up and
provide a sharp breast-thoracic angle, which is crucial in creating natural
looking ptosis of the reconstructed breast.
PMID- 28497017
TI - Improving aesthetic outcomes in mastopexy with the "autoprosthesis" technique.
AB - BACKGROUND: Many techniques have been described for mastopexy, with several types
of skin incisions and parenchymal rearrangements. We present a parenchymal
rearrangement technique allowing better upper pole fullness and nipple-areola
complex (NAC) projection when performing a mastopexy, with a combination of a
superior pedicle for the NAC and an inferiorly-based parenchymal flap, the so
called "autoprosthesis". METHODS: From January 2008 to June 2015, 184 patients
underwent "autoprosthesis" mastopexy. Patients' mean ages was 42 years. The mean
follow-up period was 39 months. RESULTS: We reported no major complications. All
the patients were satisfied with their post-operative unclothed and clothed
appearance and overall body image as reported by our questionnaire. CONCLUSIONS:
The autoprosthesis technique for mastopexy is a simple and safe, technique,
allowing long-lasting results for breast projection and upper pole fullness.
PMID- 28497019
TI - Anatomical basis of pedicles in breast reduction.
AB - The mammary gland is composed of multiple tubules acinar pockets in which the
secretory layer, connective tissue stroma, and fatty tissue all respond to
hormonal and systemic influences. These structures are irrigated by three
vascular pedicle branches, from the axillary artery, internal mammary artery, and
intercostal artery. This vascular anastomotic arrangement forms the anatomical
basis of the flaps used in breast reduction techniques. The veins form a strong
subdermal network, latticed with the arterial network. The lymph vessels have
three well-defined pedicles, skin, glandular and milk ducts that drain into
internal, external, and posterior ducts. The understanding of these anatomical
structures determines the selection of different pedicles in breast volume
reduction and preservation of the nipple-areola complex circulation.
PMID- 28497018
TI - Breast implant design.
AB - Breast Augmentation remains as one of the most common procedures performed in the
United States. This article explores the evolution of breast implants with
special emphasis on the advancement of the silicone implants.
PMID- 28497020
TI - Silicone breast implant rupture: a review.
AB - Silicone breast implants have been in use for nearly 6 decades. In this time they
have undergone significant changes in design and use. They have been subject to
intense scrutiny with regard to safety and efficacy, including an almost 10 years
moratorium on their use. The current generations of implants have been followed
via the manufacturer's Core studies in order to obtain long term data regarding
safety and complications. The results of the more recent studies are compiled in
this review. Rupture rates are initially very low and begin to increase after 6-8
years of implantation. Implant rupture may be detected by physical exam,
ultrasound or magnetic resonance imaging (MRI). The majority of silicone implant
ruptures are clinically undetectable. Symptomatic patients may present with
capsular contracture, breast lumps or changes in breast shape. The most common
cause of implant rupture is instrument damage during placement. Implant rupture
may be confined to the peri-prosthetic capsule or may extravasate into the breast
tissue. Patients with ruptured implants have been studied closely and the
consensus of the literature states there are no health risks associated with
implant rupture. Symptomatic patients with ruptured implants should be offered
the choice of observation, or explantation and capsulectomy with or without
replacement.
PMID- 28497021
TI - Understanding rare adverse sequelae of breast implants: anaplastic large-cell
lymphoma, late seromas, and double capsules.
AB - Breast implant-associated anaplastic large cell lymphoma (BI-ALCL) is a distinct
type of T-cell lymphoma arising around breast implants. The United States FDA
recently updated the 2011 safety communication, warning that women with breast
implants may have a very low risk of developing ALCL adjacent to a breast
implant. According to the World Health Organization, BI-LCL is not a breast
cancer or cancer of the breast tissue; it is a lymphoma, a cancer of immune
cells. BI-ALCL is highly curable in the majority of patients. Informed consent
should include the risk of BI-ALCL with breast implant patients. Women with
breast implants are encouraged to contact their plastic surgeon if they notice
swelling, fluid collections, or unexpected changes in breast shape. Physicians
are encouraged to send suspicious peri-prosthetic fluid for CD30
immunohistochemistry, cell block cytology, and culture in symptomatic patients.
An observation from reported cases indicates a predominance of textured device
involvement. More information is needed to fully understand risk factors and
etiology. The association of bacteria and biofilm with ALCL is currently being
investigated and one theory is that biofilm may play a role in this disease
process stressing the importance of best practice techniques intraoperatively.
Recent studies have reported clinical presentation, prognosis, and treatment
outcomes with long term followup demonstrating the critical role for surgical
management.
PMID- 28497022
TI - Patients' satisfaction with anatomic polyurethane implants.
AB - This paper presents patients satisfaction using anatomical polyurethane breast
implants. We performed surgery on 525 patients, 370 of which were primary and 155
were secondary to various causes such as capsular contracture, ruptured implants,
volume changes, and incorrect positioning of the implant. The advantages of
silicone polyurethane covers shown high level of patient satisfaction, low
incidence of capsular contracture, and absence of implant rotation, and late
seroma.
PMID- 28497023
TI - The waterfall effect in breast augmentation.
AB - The 'waterfall effect' is a descriptive term to indicate a sliding ptosis of
parenchymal breast tissue over a fixed or encapsulated implant. It occurs more
frequently than surgeons anticipate and especially over the longer term after
augmentation. Certain breast implants are more prone to contribute to this
problem as are implants placed in submuscular pockets that ride high, especially
in women with anatomical musculoskeletal variance or asymmetry. This article
describes the aetiology of sliding ptosis in more detail, the relevant anatomy
and the surgical correction. Understanding the problem enables the surgeon to
plan the appropriate procedure and obtain proper informed consent. It is possible
that a two stage procedure is necessary should the upper pole of breast require a
debulk, either early (3 to 12 months) or later as the breast may slide with
ageing of the tissues. The waterfall effect of breast parenchyma over implants is
only apparent when the upper torso of the woman is undressed and she is in an
erect posture. A significant number of women are happy with this situation and
therefore no further action is required. Those that want an improved appearance
in these circumstances can try autologous fat transfer to rebulk the surrounding
tissues but generally the most likely solution involves a mastopexy with or
without implant exchange. The results are highly rewarding but the scars are the
legacy. Mastopexy augmentation is a difficult procedure and should only be
performed by experienced surgeons. Many surgeons prefer a two stage approach with
either an implant based augmentation first to limit scars and see if the patient
is happy with the outcome or a first stage mastopexy to decide whether implants
or fat graft are actually required as a secondary procedure.
PMID- 28497024
TI - Decisional pathways in breast augmentation: how to improve outcomes through
accurate pre-operative planning.
AB - Breast augmentation is the most commonly performed surgical procedure in
aesthetic plastic surgery. Accurate pre-operative planning is crucial to obtain
the best outcomes. We present our planning method deriving from a more than 30
year experience in aesthetic breast surgery, matching together patients tissues'
characteristics and patients' wishes. We schematized our planning method in an
easy-to-use flow diagram to help the decisional process in breast augmentation.
PMID- 28497025
TI - How to prevent complications in breast augmentation.
AB - No high-level evidences about the best technique or the best implant to use for
obtaining the best outcomes in aesthetic breast augmentation, with low
complications and re-interventions rates exist from available literature. In this
paper we present the actual best evidence about the etiopathogenesis of main
complications in aesthetic breast augmentation, identifying some basic rules to
follow in order to reduce complication rates in our daily activity, minimizing re
interventions, obtaining long lasting results and high women's satisfaction
levels.
PMID- 28497026
TI - CHCHD4 Regulates Intracellular Oxygenation and Perinuclear Distribution of
Mitochondria.
AB - Hypoxia is a characteristic of the tumor microenvironment and is known to
contribute to tumor progression and treatment resistance. Hypoxia-inducible
factor (HIF) dimeric transcription factors control the cellular response to
reduced oxygenation by regulating the expression of genes involved in metabolic
adaptation, cell motility, and survival. Alterations in mitochondrial metabolism
are not only a downstream consequence of HIF-signaling but mitochondria
reciprocally regulate HIF signaling through multiple means, including oxygen
consumption, metabolic intermediates, and reactive oxygen species generation.
CHCHD4 is a redox-sensitive mitochondrial protein, which we previously identified
and showed to be a novel regulator of HIF and hypoxia responses in tumors.
Elevated expression of CHCHD4 in human tumors correlates with the hypoxia gene
signature, disease progression, and poor patient survival. Here, we show that
either long-term (72 h) exposure to hypoxia (1% O2) or elevated expression of
CHCHD4 in tumor cells in normoxia leads to perinuclear accumulation of
mitochondria, which is dependent on the expression of HIF-1alpha. Furthermore, we
show that CHCHD4 is required for perinuclear localization of mitochondria and HIF
activation in response to long-term hypoxia. Mutation of the functionally
important highly conserved cysteines within the Cys-Pro-Cys motif of CHCHD4 or
inhibition of complex IV activity (by sodium azide) redistributes mitochondria
from the perinuclear region toward the periphery of the cell and blocks HIF
activation. Finally, we show that CHCHD4-mediated perinuclear localization of
mitochondria is associated with increased intracellular hypoxia within the
perinuclear region and constitutive basal HIF activation in normoxia. Our study
demonstrates that the intracellular distribution of the mitochondrial network is
an important feature of the cellular response to hypoxia, contributing to hypoxic
signaling via HIF activation and regulated by way of the cross talk between
CHCHD4 and HIF-1alpha.
PMID- 28497027
TI - Data-Based Radiation Oncology: Design of Clinical Trials in the Toxicity
Biomarkers Era.
AB - The ability to stratify patients using a set of biomarkers, which predict that
toxicity risk would allow for radiotherapy (RT) modulation and serve as a
valuable tool for precision medicine and personalized RT. For patients presenting
with tumors with a low risk of recurrence, modifying RT schedules to avoid
toxicity would be clinically advantageous. Indeed, for the patient at low risk of
developing radiation-associated toxicity, use of a hypofractionated protocol
could be proposed leading to treatment time reduction and a cost-utility
advantage. Conversely, for patients predicted to be at high risk for toxicity,
either a more conformal form or a new technique of RT, or a multidisciplinary
approach employing surgery could be included in the trial design to avoid or
mitigate RT when the potential toxicity risk may be higher than the risk of
disease recurrence. In addition, for patients at high risk of recurrence and low
risk of toxicity, dose escalation, such as a greater boost dose, or irradiation
field extensions could be considered to improve local control without severe
toxicities, providing enhanced clinical benefit. In cases of high risk of
toxicity, tumor control should be prioritized. In this review, toxicity
biomarkers with sufficient evidence for clinical testing are presented. In
addition, clinical trial designs and predictive models are described for
different clinical situations.
PMID- 28497028
TI - Inactive Gingipains from P. gingivalis Selectively Skews T Cells toward a Th17
Phenotype in an IL-6 Dependent Manner.
AB - Gingipain cysteine proteases are considered key virulence factors of
Porphyromonas gingivalis. They significantly influence antibacterial and
homeostatic functions of macrophages, neutrophils, the complement system, and
cytokine networks. Recent data indicate the role of P. gingivalis in T cell
differentiation; however, the involvement of gingipains in this process remains
elusive. Therefore, the aim of this study was to investigate the contribution of
danger signals triggered by the gingipains on the generation of Th17 cells, which
play a key role in protection against bacterial diseases but may cause chronic
inflammation and bone resorption. To this end we compared the effects of the wild
type strain of P. gingivalis (W83) with its isogenic mutant devoid of gingipain
activity (DeltaKDeltaRAB), and bacterial cells pretreated with a highly-specific
inhibitor of gingipains activity (KYTs). Antigen presenting cells (APCs), both
professional (dendritic cells), and non-professional (gingival keratinocytes),
exposed to viable bacteria expressed high amounts of cytokines (IL-6, IL-21, IL
23). These cytokines are reported to either stimulate or balance the Th17
dependent immune response. Surprisingly, cells infected with P. gingivalis devoid
of gingipain activity showed increased levels of all tested cytokines compared to
bacteria with fully active enzymes. The effect was dependent on both the
reduction of cytokine proteolysis and the lack of cross-talk with other bacterial
virulence factors, including LPS and fimbriae that induce de novo synthesis of
cytokines. The profile of lymphocyte T differentiation from naive T cells showed
enhanced generation of Th17 in response to bacteria with inactive gingipains.
Moreover, we found that gingipain-dependent induction of Th17 cells was highly
specific, since other T cell-subsets remained unchanged. Finally, inhibition of
IL-6 signaling in dendritic cells led to a significant depletion of the Th17
population. Cumulatively, this study revealed a previously undisclosed role of
gingipain activity in the process of Th17 differentiation reliant on blocking
signaling through IL-6. Since inactivation of gingipains accelerates the skewing
of T cells toward Th17 cells, which are detrimental in periodontitis, IL-6
signaling may serve as an attractive target for treatment of the disease.
PMID- 28497031
TI - The comparative study of resonance disorders for Vietnamese and Korean cleft
palate speakers using nasometer.
AB - BACKGROUND: Nasalance is used to evaluate the velopharyngeal incompetence in
clinical diagnoses using a nasometer. The aim of this study is to find the
nasalance differences between Vietnamese cleft palate children and Korean cleft
palate children by measuring the nasalance of five oral vowels. METHODS: Ten
Vietnamese cleft palate children after surgery, three Vietnamese children for the
control group, and ten Korean cleft palate children after surgery with the same
age participated in this experimentation. Instead of Korean control, the standard
value of Korean version of the simplified nasometric assessment procedures
(kSNAP) was used. RESULT: The results are as follows: (1) the highest nasalance
score among the Vietnamese normal vowels is the low vowel /a/; however, that of
Korean normal vowels is the high vowel /i/. (2) The average nasalance score of
Korean cleft palate vowels is 18% higher than that of Vietnamese cleft palate
vowels. There was a nasalance score of over 45% among the vowels /e/ and /i/ in
Vietnamese cleft palate patients and /i/, /o/, and /u/ in Korean cleft palate
patients. CONCLUSION: These different nasalance scores of the same vowels seem to
cause an ethnic difference between Vietnamese and Korean cleft palate children.
PMID- 28497032
TI - A Tribute to Bernardo Ochoa, MD.
PMID- 28497029
TI - Reciprocal Interactions between Nematodes and Their Microbial Environments.
AB - Parasitic nematode infections are widespread in nature, affecting humans as well
as wild, companion, and livestock animals. Most parasitic nematodes inhabit the
intestines of their hosts living in close contact with the intestinal microbiota.
Many species also have tissue migratory life stages in the absence of severe
systemic inflammation of the host. Despite the close coexistence of helminths
with numerous microbes, little is known concerning these interactions. While the
environmental niche is considerably different, the free-living nematode
Caenorhabditis elegans (C. elegans) is also found amongst a diverse microbiota,
albeit on decaying organic matter. As a very well characterized model organism
that has been intensively studied for several decades, C. elegans interactions
with bacteria are much more deeply understood than those of their parasitic
counterparts. The enormous breadth of understanding achieved by the C. elegans
research community continues to inform many aspects of nematode parasitology.
Here, we summarize what is known regarding parasitic nematode-bacterial
interactions while comparing and contrasting this with information from work in
C. elegans. This review highlights findings concerning responses to bacterial
stimuli, antimicrobial peptides, and the reciprocal influences between nematodes
and their environmental bacteria. Furthermore, the microbiota of nematodes as
well as alterations in the intestinal microbiota of mammalian hosts by helminth
infections are discussed.
PMID- 28497033
TI - Intrapulmonary Percussive Ventilation as an Airway Clearance Technique during
Venoarterial Extracorporeal Life Support in an Infant with Pertussis.
AB - Initiation of extracorporeal life support (ECLS) is often followed by complete
opacification of pulmonary parenchyma and volume loss. The optimal mechanical
ventilator management and lung recruitment strategy of a pediatric patient
requiring extracorporeal membrane oxygenation is not known. We present a case of
a 4-week old infant who developed a severe pertussis infection requiring ECLS.
The severity of his illness and pertussis infection-associated intraluminal
bronchiole obstruction made medical management challenging. In addition to lung
protection ventilator strategies and bronchoscopy, intrapulmonary percussive
ventilation was initiated to facilitate lung recruitment. This was associated
with precipitous incremental improvement in lung compliance and eventual
liberation from venoarterial ECLS.
PMID- 28497030
TI - FDA-approved immunosuppressants targeting staphylococcal superantigens:
mechanisms and insights.
AB - Immunostimulating staphylococcal enterotoxin B (SEB) and related superantigenic
toxins cause diseases in human beings and laboratory animals by hyperactivating
cells of the immune system. These protein toxins bind to the major
histocompatibility complex class II (MHC II) molecules and specific Vbeta regions
of T-cell receptors (TCRs), resulting in the stimulation of both
monocytes/macrophages and T lymphocytes. The bridging of TCR with MHC II
molecules by superantigens triggers intracellular signaling cascades, resulting
in excessive release of proinflammatory mediators and massive polyclonal T-cell
proliferation. The early induction of tumor necrosis factor alpha, interleukin 1
(IL-1), interleukin 2 (IL-2), interferon gamma (IFNgamma), and macrophage
chemoattractant protein 1 promotes fever, inflammation, and multiple organ
injury. The signal transduction pathways for staphylococcal superantigen-induced
toxicity downstream from TCR/major histocompatibility complex (MHC) ligation and
interaction of cell surface co-stimulatory molecules include the mitogen
activated protein kinase cascades and cytokine receptor signaling, activating
nuclear factor kappaB (NFkappaB) and the phosphoinositide 3-kinase/mammalian
target of rapamycin pathways. Knowledge of host regulation within these activated
pathways and molecules initiated by SEB and other superantigens enables the
selection of US Food and Drug Administration (FDA)-approved drugs to interrupt
and prevent superantigen-induced shock in animal models. This review focuses on
the use of FDA-approved immunosuppressants in targeting the signaling pathways
induced by staphylococcal superantigens.
PMID- 28497034
TI - Comparison of Fluoride Levels in Tap and Bottled Water and Reported Use of
Fluoride Supplementation in a United States-Mexico Border Community.
AB - BACKGROUND: Compared to the general United States (U.S.) population, Arizona
counties along the U.S.-Mexico border have a higher prevalence of dental caries,
which can be reduced with adequate fluoride exposure. Because of concern
regarding local tap water quality, fluoride-free bottled water consumption is
common in this region, raising concern that families are not receiving adequate
fluoride to promote dental health. OBJECTIVE: To evaluate the levels of fluoride
in tap and bottled water as well as the use of fluoride supplements in an Arizona
border community. METHODS: Low-income Latino households (n = 90) who report use
of bottled water as their primary source of water intake were recruited.
Participants completed a questionnaire about their and their children's dental
histories and use of fluoride supplements. Water samples (bottled and tap) were
collected from a subset of households (n = 30) for analysis of fluoride. RESULTS:
Fluoride detection levels were significantly greater (p = 0.02, Fisher's exact
test) in tap water (average = 0.49 mg/dL) than in bottled water, yet, the
majority (22/30) were below the range for optimal dental health (0.7-1.2 mg/L).
Concentration of fluoride in the majority (29/30) of bottled water samples was
below the quantitative detection limit of 0.4 mg/L. Children were significantly
less likely to have dental caries if they received fluoride varnishing treatments
(p = 0.01, Fisher's exact test), lived in households that reported using
fluoridated mouthwash (p < 0.001, Fisher's exact test), their parents received
fluoride education (p = 0.01, Fisher's exact test), and their parents reported
visiting a dentist yearly (p < 0.001, Fisher's exact test). Furthermore, none of
the participants reported receiving recommendations from health-care providers
about fluoride supplementation or variance in content by the type of water
consumed. CONCLUSION: Although fluoride was significantly more likely to be
detected in tap than bottled water, neither water source in this border community
is likely to provide enough fluoride for optimal dental health. Low-income
children in this region may benefit from regular access to fluoride varnishing
treatments and/or use of fluoridated mouthwash, interventions that could be
tested in future well-designed trials.
PMID- 28497035
TI - Postpartum Depressive Symptoms and Associated Factors in Married Women: A Cross
sectional Study in Danang City, Vietnam.
AB - INTRODUCTION: Postpartum depression (PPD) among women is a common mental health
concern. It occurs at a time of major life change, coupled with the increased
responsibilities associated with the care of a newborn infant. In Vietnam, the
prevalence of depressive symptoms after giving birth has not been fully
investigated. Research in the Northern provinces, in Ho Chi Minh City, and in Hue
suggests postnatal depressive symptoms among women are common. This research aims
to (1) estimate the prevalence of PPD symptoms among married women in one Vietnam
city (Danang) and (2) identify the social and personal factors associated with
postpartum depressive symptoms. METHODS: This cross-sectional study was conducted
from July 2013 to August 2014 in 10 wards of Hai Chau District, Danang. A total
of 600 mothers who gave birth 4 weeks to 6 months prior to being interviewed were
recruited. Interviews were conducted using structured questionnaires, which
included several dimensions: demographics, family living arrangements,
expectations of pregnancy, expectations of infant gender, the woman's
relationship with her husband, exercise after birth, infant health, and anxiety
about matters other than the birth. The Edinburgh Postpartum Depression Scale
(EPDS) was used to examine PPD symptoms, with a cutoff point of 12/13. RESULTS:
EPDS scores indicated the prevalence of PPD symptoms was 19.3% (95% CI: 16.16
22.50). Among women with PPD symptoms, 37.9% had suicidal thoughts in the
previous seven days. Multivariate logistic regression indicated that the
following key factors were significantly associated with PPD symptoms: Not being
able to rely on their husband for help, having a husband who does not spend time
to discuss problems, having anxiety about matters other than the birth, not
exercising after giving birth, and having an ill baby. CONCLUSION: These findings
should be interpreted in relation to other recent research in Vietnam. A
consistent pattern of prevalence estimates and associated social factors is
emerging that has implications for the postpartum care of mothers.
PMID- 28497036
TI - Reversed Phase HPLC-DAD Profiling of Carotenoids, Chlorophylls and Phenolic
Compounds in Adiantum capillus-veneris Leaves.
AB - Adiantum capillus-veneris is important endangered fern species with several
medicinal properties. In this study, the leaves samples were extracted and
separated using reversed phase HPLC with DAD for carotenoids, chlorophylls and
phenolic compounds. Separation of carotenoids and chlorophylls were carried out
using a tertiary gradient system of water, MTBE and methanol-water, while a
binary gradient system of methanol-water-acetic acid was used for phenolic
profiling. Results revealed eight carotenoids, four pheophytins, and two
chlorophylls. Lutein (806.0 MUg/g), chlorophyll b' (410.0 MUg/g), chlorophyll a
(162.4 MUg/g), 9'-Z-neoxanthin (142.8 MUg/g) and all-E-violaxanthin (82.2 MUg/g)
were present in higher amounts. The relatively high amounts of lutein may be one
of the key indicator of beneficial antioxidant properties. The phenolic profile
revealed a total of 13 compounds, namely 4-hydroxybenzoic acid, chlorogenic acid,
caftaric acid, kaempferol glycosides, p-coumaric acid, rosmarinic acid, 5
caffeoylquinic acid, and quercetin glycosides. Kaempferol-3-sophorotrioside (58.7
mg/g), chlorogenic acid (28.5 mg/g), 5-O-caffeoylquinic acid (18.7 mg/g),
coumaric acid (11.2 mg/g), and its derivative (33.1 mg/g) were present in high
amounts. These results suggest that the reversed phase HPLC profiling of Adiantum
leaves provides a better understanding in to the actual composition of bioactive
compounds, which may be responsible for the potential medicinal properties.
Adiantum leaves rich in important bioactive phytochemicals can be used as a
possible source of nutraceuticals or as a functional food ingredient.
PMID- 28497037
TI - Timeliness of Operating Room Case Planning and Time Utilization: Influence of
First and To-Follow Cases.
AB - Resource and cost constraints in hospitals demand thorough planning of operating
room schedules. Ideally, exact start times and durations are known in advance for
each case. However, aside from the first case's start, most factors are hard to
predict. While the role of the start of the first case for optimal room
utilization has been shown before, data for to-follow cases are lacking. The
present study therefore aimed to analyze all elective surgery cases of a
university hospital within 1 year in search of visible patterns. A total of
14,014 cases scheduled on 254 regular working days at a university hospital
between September 2015 and August 2016 underwent screening. After eliminating 112
emergencies during regular working hours, 13,547 elective daytime cases were
analyzed, out of which 4,346 ranked first, 3,723 second, and 5,478 third or
higher in the daily schedule. Also, 36% of cases changed start times from the day
before to 7:00 a.m., with half of these (52%) resulting in a delay of more than
15 min. After 7:00 a.m., 87% of cases started more than 10 min off schedule, with
26% being early and 74% late. Timeliness was 15 +/- 72 min (mean +/- SD) for
first, 21 +/- 84 min for second, and 25 +/- 93 min for all to-follow cases,
compared to preoperative day planning, and 21 +/- 45, 23 +/- 61, and 19 +/- 74
min compared to 7:00 a.m. status. Start time deviations were also related to
procedure duration, with cases of 61-90 min duration being most reliable
(deviation 9.8 +/- 67 min compared to 7:00 a.m.), regardless of order. In
consequence, cases following after 61-90 min long cases had the shortest
deviations of incision time from schedule (16 +/- 66 min). Taken together, start
times for elective surgery cases deviate substantially from schedule, with first
and second cases falling into the highest mean deviation category. Second cases
had the largest deviations from scheduled times compared to first and all to
follow cases. While planned vs. actual start times differ among specialties,
cases of 61-90 min duration had the most reliable start times, with neither
shorter nor longer cases seeming to improve timeliness of start times.
PMID- 28497038
TI - Epigenetics and Vascular Diseases: Influence of Non-coding RNAs and Their
Clinical Implications.
AB - Epigenetics refers to heritable mechanisms able to modulate gene expression that
do not involve alteration of the genomic DNA sequence. Classically, mechanisms
such as DNA methylation and histone modifications were part of this
classification. Today, this field of study has been expanded and includes also
the large class of non-coding RNAs (ncRNAs). Indeed, with the extraordinary
possibilities introduced by the next-generation sequencing approaches, our
knowledge of the mammalian transcriptome has greatly improved. Today, we have
identifying thousands of ncRNAs, and unsurprisingly, a direct association between
ncRNA dysregulation and development of cardiovascular pathologies has been
identified. This class of gene modulators is further divided into short-ncRNAs
and long-non-coding RNAs (lncRNAs). Among the short-ncRNA sub-group, the best
characterized players are represented by highly conserved RNAs named microRNAs
(miRNAs). miRNAs principally inhibit gene expression, and their involvement in
cardiovascular diseases has been largely studied. On the other hand, due to the
different roles played by lncRNAs, their involvement in cardiovascular pathology
development is still limited, and further studies are needed. For instance, in
order to define their roles in the cellular processes associated with the
development of diseases, we need to better characterize the details of their
mechanisms of action; only then might we be able to develop innovative
therapeutic strategies. In this review, we would like to give an overview of the
current knowledge on the function of ncRNAs and their involvement in the
development of vascular diseases.
PMID- 28497039
TI - High Glucose Promotes CD36 Expression by Upregulating Peroxisome Proliferator
Activated Receptor gamma Levels to Exacerbate Lipid Deposition in Renal Tubular
Cells.
AB - Diabetic kidney disease (DKD) appears to be closely related to lipid deposition
in kidney. The aim of this study was to determine whether high glucose (HG)
exacerbated lipid deposition by increasing CD36 expression via AKT-PPARgamma
signaling pathway. Our results showed that HG activated AKT signaling pathway,
followed by an increase in PPARgamma that induced CD36 overexpression, ultimately
causing lipid deposition in HK-2 cells. We also found that inhibition of AKT
PPARgamma signaling pathway or knockdown of CD36 could reduce HG-induced lipid
accumulation in HK-2 cells. These results indicated that AKT-PPARgamma signaling
pathway mediated HG-induced lipid deposition by upregulating CD36 expression in
HK-2 cells and that inhibition of AKT-PPARgamma signaling pathway had the
potential beneficial effects of reducing lipid deposition in diabetic kidney.
PMID- 28497040
TI - Metabolic Syndrome and Hypertension Resulting from Fructose Enriched Diet in
Wistar Rats.
AB - Increased sugar consumption, especially fructose, is strongly related to the
development of type 2 diabetes (T2D) and metabolic syndrome. The aim of this
study was to evaluate long term effects of fructose supplementation on Wistar
rats. Three-week-old male rats were randomly divided into 2 groups: control (C; n
= 14) and fructose fed (FF; n = 18), with a fructose enriched drink (20-25% w/v
fructose in water) for 21 weeks. Systolic blood pressure, fasting glycemia, and
bodyweight were regularly measured. Glucose tolerance was evaluated three times
using an oral glucose tolerance test. Insulin levels were measured concomitantly
and insulin resistance markers were evaluated (HOMA 2-IR, Insulin Sensitivity
Index for glycemia (ISI-gly)). Lipids profile was evaluated on plasma. This
fructose supplementation resulted in the early induction of hypertension without
renal failure (stable theoretical creatinine clearance) and in the progressive
development of fasting hyperglycemia and insulin resistance (higher HOMA 2-IR,
lower ISI-gly) without modification of glucose tolerance. FF rats presented
dyslipidemia (higher plasma triglycerides) and early sign of liver malfunction
(higher liver weight). Although abdominal fat weight was increased in FF rats, no
significant overweight was found. In Wistar rats, 21 weeks of fructose
supplementation induced a metabolic syndrome (hypertension, insulin resistance,
and dyslipidemia) but not T2D.
PMID- 28497041
TI - Annexin A3 as a Prognostic Biomarker for Breast Cancer: A Retrospective Study.
AB - To validate the correlation between ANXA3 expression and prognosis in breast
cancer, a retrospective study encompassing 309 breast cancer patients was
performed. The expression of ANXA3 was determined by the immunohistochemical
examination of tissue sections by the Max VisionTM method. The ANXA3 levels in
the patient samples were validated for the prognosis based on age, menopause
status, tumor size, tumor node, metastasis stage, the number of lymphatic
metastases, oncology grade, and molecular subtyping. An elevated expression of
ANXA3 was detected in breast cancer samples, compared to adjacent tissue samples,
and significant correlation depending on the number of lymphatic metastases (P =
0.001) and histological grade (P = 0.004) was observed. The number of lymphatic
metastases and ANXA3 expression were identified as independent risk factors
affecting the disease-free survival and overall survival. Significantly (P <
0.002) higher level of ANXA3 was detected in triple-negative breast cancer
compared to other subtypes. There was no significant (P > 0.05) change in the
expression of ANXA3 with respect to age, menopausal status, tumor size, and
clinical stage. The findings implicate the expression of ANXA3 with the natural
progression of breast cancer and associate it with increased lymphatic
metastasis. The study validates the use of ANXA3 as a potential prognosis
biomarker for breast cancer.
PMID- 28497042
TI - Scientific Evidence for Different Options for GDM Screening and Management:
Controversies and Review of the Literature.
AB - Background. Gestational diabetes (GDM) affects up to 7% of pregnant women and is
associated with several maternal and perinatal morbidities. International
organizations suggest several different recommendations regarding how to screen
and to manage GDM. Objective. We aimed to analyze the most important and employed
guidelines about screening and management of GDM and we investigated existing
related literature. Results. We found several different criteria for screening
for GDM, for monitoring GDM, and for starting pharmacological therapy. When using
IADPSG criteria, GDM rate increased, perinatal outcomes improved, and screening
became cost-effective. Compared to no treatment, treatment of women meeting
criteria for GDM by IADPSG criteria but not by other less strict criteria has
limited evidence for an effect on adverse pregnancy outcomes.
PMID- 28497043
TI - The Effect of Different Pollination on the Expression of Dangshan Su Pear
MicroRNA.
AB - The high-throughput sequencing of pear "Dangshan Su" * "Yali" (whose fruits
lignin and stone cell content are high and quality is poor) and pear "Dangshan
Su" * "Wonhwang" (whose fruits with low content of lignin and stone cell and the
quality are better ) found that the expressions of these two miRNAs (pyr-1809 and
pyr-novel-miR-144-3p) were significantly different; their corresponding target
genes encode two kinds of laccase (Pbr018935.1 and Pbr003857.1). qRT-PCR results
showed that these two enzymes are involved in the formation of lignin and stone
cells and the existence of these two miRNAs has a negative effect on them. It was
concluded that the effect of pollination on the development of stone cells may
affect the synthesis of lignin, through the regulation of laccase controlled by
miRNAs, and ultimately affect the formation of stone cell and fruit quality.
PMID- 28497044
TI - Predicting the Types of Ion Channel-Targeted Conotoxins Based on AVC-SVM Model.
AB - The conotoxin proteins are disulfide-rich small peptides. Predicting the types of
ion channel-targeted conotoxins has great value in the treatment of chronic
diseases, epilepsy, and cardiovascular diseases. To solve the problem of
information redundancy existing when using current methods, a new model is
presented to predict the types of ion channel-targeted conotoxins based on AVC
(Analysis of Variance and Correlation) and SVM (Support Vector Machine). First,
the F value is used to measure the significance level of the feature for the
result, and the attribute with smaller F value is filtered by rough selection.
Secondly, redundancy degree is calculated by Pearson Correlation Coefficient. And
the threshold is set to filter attributes with weak independence to get the
result of the refinement. Finally, SVM is used to predict the types of ion
channel-targeted conotoxins. The experimental results show the proposed AVC-SVM
model reaches an overall accuracy of 91.98%, an average accuracy of 92.17%, and
the total number of parameters of 68. The proposed model provides highly useful
information for further experimental research. The prediction model will be
accessed free of charge at our web server.
PMID- 28497045
TI - High Rate of Deformed Larvae among Gynogenetic Brown Trout (Salmo trutta m.
fario) Doubled Haploids.
AB - Mitotic gynogenesis results in the production of fully homozygous individuals in
a single generation. Since inbred fish were found to exhibit an increased
frequency of body deformations that may affect their survival, the main focus of
this research was to evaluate the ratio of individuals with spinal deformities
among gynogenetic doubled haploids (DHs) brown trout as compared to
nonmanipulated heterozygous individuals. Gynogenetic development was induced by
the activation of brown trout eggs by UV-irradiated homologous and heterologous
(rainbow trout) spermatozoa. The subsequent exposure of the activated eggs to the
high hydrostatic pressure disturbed the first cleavage in gynogenetic zygotes and
enabled duplication of the maternal haploid set of chromosomes. The survival rate
was significantly higher among gynogenetic brown trout hatched from eggs
activated with the homologous UV-irradiated spermatozoa when compared to DHs
hatched from eggs activated by the heterologous spermatozoa. More than 35% of the
gynogenetic larvae exhibited body deformities, mostly lordosis and scoliosis. The
percentage of malformed brown trout from the control group did not exceed 15%.
The increased number of deformed larvae among DHs brown trout suggested rather a
genetic background of the disease related to the fish spine deformities; however,
both genetic and environmental factors were discussed as a cause of such
conditions in fish.
PMID- 28497046
TI - Corrigendum to "Quantitative Evaluation and Selection of Reference Genes for
Quantitative RT-PCR in Mouse Acute Pancreatitis".
AB - [This corrects the article DOI: 10.1155/2016/8367063.].
PMID- 28497047
TI - Association Study of Gut Flora in Coronary Heart Disease through High-Throughput
Sequencing.
AB - Objectives. We aimed to explore the impact of gut microbiota in coronary heart
disease (CHD) patients through high-throughput sequencing. Methods. A total of 29
CHD in-hospital patients and 35 healthy volunteers as controls were included.
Nucleic acids were extracted from fecal samples, followed by alpha diversity and
principal coordinate analysis (PCoA). Based on unweighted UniFrac distance
matrices, unweighted-pair group method with arithmetic mean (UPGMA) trees were
created. Results. After data optimization, an average of 121312 +/- 19293 reads
in CHD patients and 234372 +/- 108725 reads in controls was obtained. Reads
corresponding to 38 phyla, 90 classes, and 584 genera were detected in CHD
patients, whereas 40 phyla, 99 classes, and 775 genera were detected in controls.
The proportion of phylum Bacteroidetes (56.12%) was lower and that of phylum
Firmicutes was higher (37.06%) in CHD patients than those in the controls (60.92%
and 32.06%, P < 0.05). PCoA and UPGMA tree analysis showed that there were
significant differences of gut microbial compositions between the two groups.
Conclusion. The diversity and compositions of gut flora were different between
CHD patients and healthy controls. The incidence of CHD might be associated with
the alteration of gut microbiota.
PMID- 28497048
TI - Antimicrobial Resistance Patterns in Women with Positive Urine Culture: Does
Menopausal Status Make a Significant Difference?
AB - Aim. Urinary tract infection (UTI) is considered one of the most common bacterial
infections in women. The aim of this study was to investigate the types of
uropathogens present, as well as the degree of antimicrobial drug resistance seen
among premenopausal (n = 2748) and postmenopausal (n = 1705) women with
uncomplicated UTI. Methods. Urinary samples (n = 4453) collected from women with
UTI were analyzed in terms of uropathogens present. These were considered as
positive if bacterial growth was >=105 colony forming units (CFUs)/mL.
Susceptibility and resistance testing for commonly used antibiotics was
subsequently assessed. Results. The most common uropathogens cultured from urine
samples were Escherichia coli (65.5%), followed by Enterococcus faecalis (12.2%),
Klebsiella pneumoniae (4.7%), and Proteus mirabilis (4.2%). The resistance to
ampicillin exceeded 40%, independently of menopausal status. Of note, resistance
to ciprofloxacin exceeded 25% among postmenopausal patients. Moreover, resistance
of all uropathogens to commonly used antimicrobials was significantly higher in
postmenopausal women. Conclusion. Due to the high resistance rate, ampicillin,
ciprofloxacin, and the trimethoprim/sulfamethoxazole combination should be
avoided in treating postmenopausal women affected by UTI without being indicated
by initial urine culture report. Finally, cephalexin and cefuroxime are promising
alternatives as initial treatment in postmenopausal women.
PMID- 28497049
TI - Biomechanical Analysis of Cuboid Osteotomy Lateral Column Lengthening for Stage
II B Adult-Acquired Flatfoot Deformity: A Cadaveric Study.
AB - Purpose. To investigate the effect of cuboid osteotomy lateral column lengthening
(LCL) for the correction of stage II B adult-acquired flatfoot deformity in
cadaver. Methods. Six cadaver specimens were loaded to 350 N. Flatfoot models
were established and each was evaluated radiographically and pedobarographically
in the following conditions: (1) intact foot, (2) flatfoot, and (3) cuboid
osteotomy LCL (2, 3, 4, and 5 mm). Results. Compared with the flatfoot model, the
LCLs showed significant correction of talonavicular coverage on anteroposterior
radiographs and talus-first metatarsal angle on both anteroposterior and lateral
radiographs (p < .05). Compared with the intact foot, the above angles of the
LCLs showed no significant difference except the 2 mm LCL. In terms of forefoot
pressure, medial pressure of the 2 mm LCL (p = .044) and lateral pressure of the
3, 4, and 5 mm LCLs showed statistical differences (p < .05), but lateral
pressure of the 3 mm LCL was not more than the intact foot as compared to the 4
and 5 mm LCLs, which was less than medial pressure. Conclusion. Cuboid osteotomy
LCL procedure avoids damage to subtalar joint and has a good effect on correction
of stage II B adult-acquired flatfoot deformity with a 3 mm lengthening in
cadavers.
PMID- 28497050
TI - The Role of Biologically Active Ingredients from Natural Drug Treatments for
Arrhythmias in Different Mechanisms.
AB - Arrhythmia is a disease that is caused by abnormal electrical activity in the
heart rate or rhythm. It is the major cause of cardiovascular morbidity and
mortality. Although several antiarrhythmic drugs have been used in clinic for
decades, their application is often limited by their adverse effects. As a
result, natural drugs, which have fewer side effects, are now being used to treat
arrhythmias. We searched for all articles on the role of biologically active
ingredients from natural drug treatments for arrhythmias in different mechanisms
in PubMed. This study reviews 19 natural drug therapies, with 18 active
ingredient therapies, such as alkaloids, flavonoids, saponins, quinones, and
terpenes, and two kinds of traditional Chinese medicine compound (Wenxin-Keli and
Shensongyangxin), all of which have been studied and reported as having
antiarrhythmic effects. The primary focus is the proposed antiarrhythmic
mechanism of each natural drug agent. Conclusion. We stress persistent vigilance
on the part of the provider in discussing the use of natural drug agents to
provide a solid theoretical foundation for further research on antiarrhythmia
drugs.
PMID- 28497051
TI - MicroRNA Expression Signature in Human Calcific Aortic Valve Disease.
AB - Altered microRNA (miRNA, miR) expression has been related to many disease
processes; however, the miRNA expression signature in calcific aortic valve
disease (CAVD) is unclear. In this study, microarrays were used to determine the
miRNA expression signature of tissue samples from healthy individuals (n = 4) and
patients with CAVD (n = 4). TargetScan, PITA, and microRNAorg 3-way databases
were used to predict the potential target genes. DIANA-miRPath was used to
incorporate the aberrant miRNAs into gene pathways. miRNA microarrays identified
92 differentially expressed miRNAs in CAVD tissues. The principal component
analysis (PCA) of these samples and the unsupervised hierarchical clustering
analysis based on the 92 aberrantly expressed miRNAs noted that miRNA expression
could be categorized into two well-defined clusters that corresponded to healthy
control and CAVD. Bioinformatic analysis showed the miRNA targets and potential
molecular pathways. Collectively, our study reported the miRNA expression
signature in CAVD and may provide potential therapeutic targets for CAVD.
PMID- 28497052
TI - Etiological and Resistance Profile of Bacteria Involved in Urinary Tract
Infections in Young Children.
AB - Background. The objective of this study was to identify the bacteria most
frequently responsible for urinary tract infection (UTI) in the population of
under-2-year-olds in our geographic area and to evaluate the activity of
antibiotics widely used for UTI treatment during a 4-year study period. Materials
and Methods. A retrospective analysis was conducted of data on the identification
and susceptibility of microorganisms isolated in urine samples from children
under 2 years of age. Results. A total of 1,045 uropathogens were isolated.
Escherichia coli accounted for the majority (60.3%) of these, followed by
Enterococcus faecalis (22.4%) and Klebsiella spp. (6.5%). The highest E. coli
susceptibility rates (>90%) were to piperacillin-tazobactam, cefuroxime,
cefotaxime, ceftazidime, imipenem, gentamicin, nitrofurantoin, and fosfomycin,
and the lowest were to amoxicillin-clavulanic acid and cotrimoxazole. Among all
bacteria isolated, we highlight the overall high activity of piperacillin
tazobactam, imipenem, nitrofurantoin, and fosfomycin against both community and
hospital isolates and the reduced activity of amoxicillin-clavulanic acid,
cephalosporins, gentamicin, and cotrimoxazole. There was no significant change in
the total activity of any of the studied antibiotics over the 4-year study
period. Conclusion. Empiric treatment with amoxicillin-clavulanic acid,
cotrimoxazole, cephalosporins, and gentamicin may be inadequate due to their
limited activity against uropathogens in our setting.
PMID- 28497053
TI - Numerical Evaluation of Image Contrast for Thicker and Thinner Objects among
Current Intraoral Digital Imaging Systems.
AB - The purpose is to evaluate the performance of current intraoral digital detectors
in detail using a precise phantom and new method. Two aluminum step wedges in 0.5
mm steps were exposed by two photostimulable phosphor plate (PSP) systems-one
with automatic exposure compensation (AEC) and the other without AEC-and a CCD
sensor. Images were obtained with 3 doses at 60 kV. The effect of metallic
material also was evaluated. The contrast-to-noise ratio (CNR) for thinner steps
and the low contrast value (LCV) for thicker steps were obtained. The CCD system
was the best under all conditions (P < 0.001), although the Gray value was
sensitive to the dose, and the Gray value-dose relation varied greatly. The PSP
system with AEC was superior to that without AEC for the LCV (P < 0.001) but was
inferior to it regarding the CNR (P < 0.001). CNR and LCV in the PSP system
without AEC were not affected by the metallic plate. Intraoral digital imaging
systems should be chosen according to their diagnostic purpose. PSP system with
AEC may be the best for detecting molar proximal caries, whereas the PSP system
without AEC may be better for evaluating small bone regeneration in periodontal
disease. The CCD system provided the best performance.
PMID- 28497054
TI - Electrical Stimulation for Wound-Healing: Simulation on the Effect of Electrode
Configurations.
AB - Endogenous electric field is known to play important roles in the wound-healing
process, mainly through its effects on protein synthesis and cell migration. Many
clinical studies have demonstrated that electrical stimulation (ES) with steady
direct currents is beneficial to accelerating wound-healing, even though the
underlying mechanisms remain unclear. In the present study, a three-dimensional
finite element wound model was built to optimize the electrode configuration in
ES. Four layers of the skin, stratum corneum, epidermis, dermis, and subcutis,
with defined thickness and electrical properties were modeled. The main goal was
to evaluate the distributions of exogenous electric fields delivered with direct
current (DC) stimulation using different electrode configurations such as sizes
and positions. Based on the results, some guidelines were obtained in designing
the electrode configuration for applications of clinical ES.
PMID- 28497055
TI - Indigenous Wildlife Rabies in Taiwan: Ferret Badgers, a Long Term Terrestrial
Reservoir.
AB - The emerging disease of rabies was confirmed in Taiwan ferret badgers (FBs) and
reported to the World Organization for Animal Health (OIE) on July 17, 2013. The
spread of wildlife rabies can be related to neighborhood countries in Asia. The
phylogenetic analysis was conducted by maximum likelihood (ML) methods and the
Bayesian coalescent approach based on the glycoprotein (G) and nucleoprotein (N)
genes. The phylogeographic and spatial temporal dynamics of viral transmission
were determined by using SPREAD, QGIS. Therefore, the origin and the change with
time of the viruses can be identified. Results showed the rabies virus of FB
strains in Taiwan is a unique clade among other strains in Asia. According to the
phylogeographic coalescent tree, three major genotypes of the FB rabies virus
have circulated in three different geographical areas in Taiwan. Two genotypes
have distributed into central and southern Taiwan between two ecological river
barriers. The third genotype has been limited in southeastern Taiwan by the
natural mountain barrier. The diversity of FB rabies viruses indicates that the
biological profile of FBs could vary in different geographical areas in Taiwan.
An enhanced surveillance system needs to be established near the currently
identified natural barriers for early warnings of the rabies virus outbreak in
Taiwan.
PMID- 28497056
TI - Direction-Dependent Effects of Combined Static and ELF Magnetic Fields on Cell
Proliferation and Superoxide Radical Production.
AB - Proliferation of human umbilical vein endothelial cells was stimulated by a
nearly vertical 60 or 120 MUT static magnetic field (MF) in comparison to cells
that were shielded against MFs. When the static field was combined with an
extremely low frequency (ELF) MF (18 Hz, 30 MUT), proliferation was suppressed by
a horizontal but not by a vertical ELF field. As these results suggested that the
effects of an ELF MF depend on its direction in relation to the static MF,
independent experiments were carried out to confirm such dependence using 50 Hz
MFs and a different experimental model. Cytosolic superoxide level in rat glioma
C6 cells exposed in the presence of a nearly vertical 33 MUT static MF was
increased by a horizontal 50 Hz, 30 MUT MF, but not affected by a vertical 50 Hz
MF. The results suggest that a weak ELF MF may interact with the static
geomagnetic field in producing biological effects, but the effect depends on the
relative directions of the static and ELF MFs.
PMID- 28497057
TI - Electrical Stimulation of Denervated Rat Skeletal Muscle Retards Capillary and
Muscle Loss in Early Stages of Disuse Atrophy.
AB - The purpose of the present study is to investigate the effects of low-frequency
electrical muscle stimulation (ES) on the decrease in muscle mass, fiber size,
capillary supply, and matrix metalloproteinase (MMP) immunoreactivity in the
early stages of denervation-induced limb disuse. Direct ES was performed on the
tibialis anterior muscle following denervation in seven-week-old male rats. The
rats were divided into the following groups: control (CON), denervation (DN), and
denervation with direct ES (DN + ES). Direct ES was performed at an intensity of
16 mA and a frequency of 10 Hz for 30 min per day, six days a week, for one week.
We performed immunohistochemical staining to determine the expression of
dystrophin, CD34, and MMP-2 in transverse sections of TA muscles. The weight,
myofiber cross-sectional area (FCSA), and capillary-to-fiber (C/F) ratio of the
tibialis anterior (TA) muscle were significantly reduced in the DN group compared
to the control and DN + ES groups. The MMP-2 positive area was significantly
greater in DN and DN + ES groups compared to the control group. These findings
suggest beneficial effects of direct ES in reducing muscle atrophy and capillary
regression without increasing MMP-2 immunoreactivity in the early stages of DN
induced muscle disuse in rat hind limbs.
PMID- 28497058
TI - Impact of an Intensive Perinatal Handwashing Promotion Intervention on Maternal
Handwashing Behavior in the Neonatal Period: Findings from a Randomized
Controlled Trial in Rural Bangladesh.
AB - One-quarter of neonatal deaths are attributed to infections. Maternal handwashing
with soap may prevent neonatal sepsis. We examined impact of intensive
handwashing promotion on handwashing behavior of mothers of neonates. In Matlab,
Bangladesh, we randomly allocated pregnant women at 28-32 weeks' gestation to
intensive handwashing promotion or control. Behavior change communicators used a
participatory approach to motivate maternal handwashing with soap and provided
soap and handwashing stations. In the neonatal period, we observed soap and water
at handwashing places and, at the end of the neonatal period, we estimated impact
on maternal handwashing by structured observation. Among 253 women enrolled,
intervention households were between 5.7 and 15.2 times as likely as control
households to have soap and water present at the handwashing station in the
baby's sleeping area. Intervention mothers washed hands with soap 4.1 times as
frequently as controls (95% CI 2.55-6.59); handwashing with soap at recommended
times was infrequent in both intervention (9%) and control (2%) groups.
Intensively promoting handwashing with soap resulted in increased availability of
soap and water at handwashing places, but only a modest increase in maternal
handwashing with soap. Novel approaches to motivating handwashing behavior to
protect newborns should be developed and evaluated.
PMID- 28497059
TI - A New Algorithm for Identifying Cis-Regulatory Modules Based on Hidden Markov
Model.
AB - The discovery of cis-regulatory modules (CRMs) is the key to understanding
mechanisms of transcription regulation. Since CRMs have specific regulatory
structures that are the basis for the regulation of gene expression, how to model
the regulatory structure of CRMs has a considerable impact on the performance of
CRM identification. The paper proposes a CRM discovery algorithm called ComSPS.
ComSPS builds a regulatory structure model of CRMs based on HMM by exploring the
rules of CRM transcriptional grammar that governs the internal motif site
arrangement of CRMs. We test ComSPS on three benchmark datasets and compare it
with five existing methods. Experimental results show that ComSPS performs better
than them.
PMID- 28497061
TI - Mining of Microbial Genomes for the Novel Sources of Nitrilases.
AB - Next-generation DNA sequencing (NGS) has made it feasible to sequence large
number of microbial genomes and advancements in computational biology have opened
enormous opportunities to mine genome sequence data for novel genes and enzymes
or their sources. In the present communication in silico mining of microbial
genomes has been carried out to find novel sources of nitrilases. The sequences
selected were analyzed for homology and considered for designing motifs. The
manually designed motifs based on amino acid sequences of nitrilases were used to
screen 2000 microbial genomes (translated to proteomes). This resulted in
identification of one hundred thirty-eight putative/hypothetical sequences which
could potentially code for nitrilase activity. In vitro validation of nine
predicted sources of nitrilases was done for nitrile/cyanide hydrolyzing
activity. Out of nine predicted nitrilases, Gluconacetobacter diazotrophicus,
Sphingopyxis alaskensis, Saccharomonospora viridis, and Shimwellia blattae were
specific for aliphatic nitriles, whereas nitrilases from Geodermatophilus
obscurus, Nocardiopsis dassonvillei, Runella slithyformis, and Streptomyces albus
possessed activity for aromatic nitriles. Flavobacterium indicum was specific
towards potassium cyanide (KCN) which revealed the presence of nitrilase homolog,
that is, cyanide dihydratase with no activity for either aliphatic, aromatic, or
aryl nitriles. The present study reports the novel sources of nitrilases and
cyanide dihydratase which were not reported hitherto by in silico or in vitro
studies.
PMID- 28497060
TI - Efficacy and Safety of L-Carnitine Treatment for Chronic Heart Failure: A Meta
Analysis of Randomized Controlled Trials.
AB - Background. Whether additional benefit can be achieved with the use of L
carnitine (L-C) in patients with chronic heart failure (CHF) remains
controversial. We therefore performed a meta-analysis of randomized controlled
trials (RCTs) to evaluate the effects of L-C treatment in CHF patients. Methods.
Pubmed, Ovid Embase, Web of Science, and Cochrane Library databases, Chinese
National Knowledge Infrastructure (CNKI) database, Wanfang database, Chinese
Biomedical (CBM) database, and Chinese Science and Technology Periodicals
database (VIP) until September 30, 2016, were identified. Studies that met the
inclusion criteria were systematically evaluated by two reviewers independently.
Results. 17 RCTs with 1625 CHF patients were included in this analysis. L-C
treatment in CHF was associated with considerable improvement in overall efficacy
(OR = 3.47, P < 0.01), left ventricular ejection fraction (LVEF) (WMD: 4.14%, P =
0.01), strike volume (SV) (WMD: 8.21 ml, P = 0.01), cardiac output (CO) (WMD:
0.88 L/min, P < 0.01), and E/A (WMD: 0.23, P < 0.01). Moreover, treatment with L
C also resulted in significant decrease in serum levels of BNP (WMD: -124.60
pg/ml, P = 0.01), serum levels of NT-proBNP (WMD: -510.36 pg/ml, P < 0.01), LVESD
(WMD: -4.06 mm, P < 0.01), LVEDD (WMD: -4.79 mm, P < 0.01), and LVESV (WMD:
20.16 ml, 95% CI: -35.65 to -4.67, P < 0.01). However, there were no significant
differences in all-cause mortality, 6-minute walk, and adverse events between L-C
and control groups. Conclusions. L-C treatment is effective for CHF patients in
improving clinical symptoms and cardiac functions, decreasing serum levels of BNP
and NT-proBNP. And it has a good tolerance.
PMID- 28497062
TI - A Clinical Retrospective Study of Distal Extension Removable Partial Denture with
Implant Surveyed Bridge or Stud Type Attachment.
AB - This study was performed to make comparative analysis of the clinical findings
between the two different types of the implant-assisted removable partial
dentures: removable partial dentures using implant surveyed bridge as an abutment
(ISBRPD) and overdenture type of removable partial denture using implant
attachment (IARPD). Implant cumulative survival rate, marginal bone resorption,
probing depth, peri-implant inflammation, bleeding, plaque, calculus, and
complications were evaluated on 24 patients who were treated with implants in
conjunction with removable partial denture and have used them for at least 1 year
(ISCRPD: n = 12; IARPD: n = 12). There was no failed implant and all implants
were functioning without clinical mobility. Marginal bone loss of ISCRPD (1.44 +/
0.57 mm) was significantly lower than that of IARPD (p < 0.05). There was no
significant difference in probing depth, peri-implant inflammation, bleeding, and
plaque between the two groups (p > 0.05), while the calculus was significantly
more observed in ISCRPD group than in IARPD group (p < 0.05). The retention loss
of IARPD was the most common complication. Within the limits of the present
study, it was found that well-planned ISBRPD was clinically appropriate.
Longitudinal and systematic clinical studies are necessary to confirm these
results.
PMID- 28497063
TI - Level of Knowledge and Practice of Mothers on Minimum Dietary Diversity Practices
and Associated Factors for 6-23-Month-Old Children in Adea Woreda, Oromia,
Ethiopia.
AB - Background. Globally, undernutrition is responsible for at least 35% of deaths in
children less than 5 years of age and estimated 6% of under-five deaths can be
prevented by ensuring optimal complementary feeding especially the dietary
diversity and meal frequency. In Ethiopia, 5% of children were fed according to
minimum standards with respect to food diversity. Objective. To assess the level
of knowledge and practice of mothers on dietary diversity practices and
associated factors for children 6-23 months in Adea woreda. Methods. Community
based cross-sectional study was conducted. A sample of 730 mothers who have
children in the age group of 6-23 months were selected using systematic sampling.
Logistic regression model was fitted in order to identify factors associated with
knowledge and practice of dietary diversity practice. Result. Of the total 700,
357 (51%) were knowledgeable on dietary diversity but 112 (16%) practiced
appropriate dietary diversity practice for their 6-23-month-old children.
Husbands' education (AOR = 2.79, 95% CI = (1.55, 5.00)), mothers' age, and
marital status were significantly associated with knowledge of mothers. Mothers'
age, husbands' education, marital status, and knowledge of mothers were
significantly associated with mothers' dietary diversity for 6-23-month-old
children. Conclusion. This study showed that approximately half of the mothers
have good knowledge on minimum dietary diversity for children 6-23 months old and
very low proportion of children 6-23 months old received diversified meal
according to Infant and Young Child Feeding indicators. It was identified that
different factors are responsible for this discrepancy.
PMID- 28497064
TI - The Effect of Surgical Intervention for Delayed Cervical Central Cord Syndrome.
AB - The authors retrospectively studied 11 patients with delayed cervical central
cord syndrome (CCS) to investigate the efficacy of the surgical intervention on
treatment for delayed CCS. The American Spinal Injury Association (ASIA) motor
scores, Japanese Orthopedic Association (JOA) scores, SF-36 scores, and
neurologic status were analyzed preoperatively and at each time point of
postoperative follow-up. The results show that patients with reversible spinal
cord injury caused by delayed central cord syndrome can recover significantly
after surgical intervention. Therefore, we suggest that surgical intervention is
still the ideal choice for delayed cervical central cord syndrome.
PMID- 28497065
TI - A Low Psoas Muscle Index before Treatment Can Predict a Poorer Prognosis in
Advanced Bladder Cancer Patients Who Receive Gemcitabine and Nedaplatin Therapy.
AB - Introduction. Gemcitabine and cisplatin (GC) is a gold-standard first-line
systemic chemotherapy for advanced urothelial carcinoma (UC). However, it may
cause severe adverse effects such as renal toxicity, gastrointestinal toxicity,
and neurotoxicity. Sarcopenia is the age-related loss of skeletal muscle mass. A
correlation between sarcopenia and the oncological prognosis has been reported.
In UC, several studies have noted that patients with sarcopenia had a greater
incidence of complications and worse survival after radical cystectomy or
chemotherapy. Our institute introduced gemcitabine and nedaplatin (GN) for UC
patients with renal failure. We investigated whether the presence of sarcopenia
predicted the prognosis of patients with advanced UC who were treated by GN
chemotherapy. Methods. A total of 27 patients (male, n = 21; female, n = 6)
received GN therapy for metastatic UC from 2005 to 2016. The institutional review
board of Yokohama City University Hospital approved this study. The psoas muscle
index (PMI, cm2/m2) was calculated using this formula: right psoas muscle area
(cm2)/the square of the body height (m2). The overall survival (OS) of the high
PMI group (male: >=2.49, female: >=2.07) and low PMI group (male: <2.49, female:
<2.07) was compared. Results. Kaplan-Meier survival curves and a log-rank test
revealed that the high PMI group had significantly better OS than the low PMI
group (p = 0.015). The mean survival of the high and low PMI groups was 561 days
and 223 days, respectively. Conclusions. In the present study, we revealed that
sarcopenia (a low psoas muscle volume) might be a predictive factor for poorer
overall survival in patients with advanced urothelial carcinoma who are
undergoing GN chemotherapy.
PMID- 28497066
TI - Morphometric Analysis of the Clavicles in Chinese Population.
AB - The clavicle has a complex geometry that makes plate fixation technically
difficult. The current study aims to measure the anatomical parameters of Chinese
clavicles as reference for plate design. One hundred clavicles were analyzed. The
clavicle bone model was reconstructed by using computed tomography images. The
length, diameters, and curvatures of the clavicle were then measured. The female
clavicle was shorter, more slender, and less curved in lateral part than the male
clavicle. There was a positive relationship between height and clavicle
parameters except lateral curve and depth. The measurements of Chinese clavicles
were generally smaller than Caucasians. The clavicle curves were correlated with
the bone length; thus consideration of the curve variations may be necessary as
designing size distribution of clavicle plate.
PMID- 28497067
TI - The Influence of Tribological Pairings and Other Factors on Migration Patterns of
Short Stems in Total Hip Arthroplasty.
AB - Over the last decade, the number of short stem total hip arthroplasty procedures
has increased. Along with the possible benefits associated with short stems is a
smaller implant-bone contact surface, which may have a negative influence on
primary stability and impair osseointegration. Previous studies observed
migration of short stems, especially within the first three months. The variables
that influence migration in short stem hip implants remain unknown. Therefore,
the purpose of this study was to associate the migration of short stems with its
possible influencing variables. Migration data from two different short stem
studies were retrospectively analyzed. Migration within the first two
postoperative years was determined by model-based Roentgen stereophotogrammetric
analysis. Migration was correlated to bearing couple, type and size of stem, size
of acetabular cup, and age, gender, weight, and height of patients using a
multiple factor analysis. Eigenvalue analysis explained 80.7% of the overall
variance for the first three dimensions. The four most dominant variables in the
first dimension were weight, stem size, acetabular cup size, and patient height
(correlations of 0.81, 0.80, 0.71, and 0.70, resp.). None of the analyzed
parameters (bearing couple, type and size of stem, size of acetabular cup, and
age, gender, weight, and height of patients) affected the migration pattern of
short stem THA with primary metaphyseal fixation.
PMID- 28497068
TI - Effects of Force Load, Muscle Fatigue, and Magnetic Stimulation on Surface
Electromyography during Side Arm Lateral Raise Task: A Preliminary Study with
Healthy Subjects.
AB - The aim of this study was to quantitatively investigate the effects of force
load, muscle fatigue, and extremely low-frequency (ELF) magnetic stimulation on
surface electromyography (SEMG) signal features during side arm lateral raise
task. SEMG signals were recorded from 18 healthy subjects on the anterior deltoid
using a BIOSEMI ActiveTwo system during side lateral raise task (with the right
arm 90 degrees away from the body) with three different loads on the forearm (0
kg, 1 kg, and 3 kg; their order was randomized between subjects). The arm
maintained the loads until the subject felt exhausted. The first 10 s recording
for each load was regarded as nonfatigue status and the last 10 s before the
subject was exhausted was regarded as fatigue status. The subject was then given
a five-minute resting between different loads. Two days later, the same
experiment was repeated on every subject, and this time the ELF magnetic
stimulation was applied to the subject's deltoid muscle during the five-minute
rest period. Three commonly used SEMG features, root mean square (RMS), median
frequency (MDF), and sample entropy (SampEn), were analyzed and compared between
different loads, nonfatigue/fatigue status, and ELF stimulation and no
stimulation. Variance analysis results showed that the effect of force load on
RMS was significant (p < 0.001) but not for MDF and SampEn (both p > 0.05). In
comparison with nonfatigue status, for all the different force loads with and
without ELF stimulation, RMS was significantly larger at fatigue (all p < 0.001)
and MDF and SampEn were significantly smaller (all p < 0.001).
PMID- 28497069
TI - Characterization of Focal Liver Lesions Indistinctive on B Mode Ultrasound:
Benefits of Contrast-Enhanced Ultrasound.
AB - Aim. The aim of this prospective study was to evaluate the additional value of
contrast-enhanced ultrasound (CEUS) in identifying and characterizing of focal
liver lesions (FLLs) that are indistinctive on B mode ultrasound (BMUS). Methods.
The study focused on 70 consecutive patients (male 46, female 24; mean age, 53.1
years +/- 10). All lesions were detected by MRI but could not be clearly
visualized by BMUS. CEUS was performed by injected SonoVue(r) (Bracco Imaging
Spa, Milan, Italy) as a quick bolus into the antecubital vein. All lesions were
proved by pathologic and MRI findings as primary or metastatic hepatic
malignancies. Results. On CEUS, 45 (64.2%) FLLs displayed arterial
hyperenhancement and 55 (78.5%) lesions showed hypoenhancement in portal venous
and late phase (PVLP). Homogeneous and complete hyperenhancement pattern during
the arterial phase is highly suspicious for HCC in liver cirrhosis (96.8%).
Arterial isoenhancement and early washout during PVLP are characteristic for
metastasis (73.3%). For recurrence lesions, arterial hyperenhancement and
isoenhancement during PVLP are more common (60%). Conclusion. CEUS may provide
added diagnostic values in FLLs appearing indistinctive on BMUS. Presence of
early arterial enhancement and washout during PVLP may be helpful for detection
of those lesions.
PMID- 28497071
TI - Advances in Research with LGBTQ Youth in Schools.
PMID- 28497070
TI - Impact of polyethylene glycol 400/propylene glycol/hydroxypropyl-guar and 0.1%
sodium hyaluronate on postoperative discomfort following cataract extraction
surgery: a comparative study.
AB - BACKGROUND: Universal postoperative guidelines for cataract extraction surgery
are yet to be introduced. Artificial tears are gaining popularity as an
additional integral component of the postoperative regime. The primary objective
of this study was to explore the impact of two prevalent artificial tear
preparations on postoperative discomfort following cataract extraction surgery.
METHODS: A total of 180 patients that underwent cataract extraction surgery were
randomly divided into three groups according to their postoperative regime: a)
Study group 1 (SG1) received a fixed combination of tobramycin and dexamethasone
(FCTD) quid for 3 weeks and, additionally polyethylene glycol 400/propylene
glycol/hydroxypropyl-guar quid, for 6 weeks, b) Study group 2 (SG2) received FCTD
quid for 3 weeks and, additionally 0.1% sodium hyaluronate provided in the
COMOD(r) device quid, for 6 weeks, and, c) Control Group (CG) received only FCTD
quid for 3 weeks. The following indexes were evaluated at three postoperative
checkpoints: 1) Subjective discomfort index (SDI) derived from four direct 10
scale Likert-type questions that were addressed to the patient and pertained to:
a) foreign body sensation (FBS), b) blinking discomfort (BD), c) stinging
sensation (SS), d) tearing sensation (TS), 2) Tear break-up time (TBUT), 3)
Central corneal thickness (CCT) and, 4) Central Corneal Sensitivity (CCS).
RESULTS: Both groups showed increased CCT values at the first examination point
and reduced CCS values at all examination points. Furthermore, both SGs had
better TBUT times at all examination points compared to CG (CG: 8.86 +/- 1.08,
SG1: 9.59 +/- 1.45, CG2: 9.45 +/- 1.33, p < 0.05). BD was significantly better in
both SGs only at the 1st week of examination, while SDI values were better until
the 3rd week and only borderline better at 6th week. Lastly, no significant
differences were detected between SGs, regarding all parameters, at all
examination points. CONCLUSION: Polyethylene glycol 400/propylene
glycol/hydroxypropyl-guar and 0.1% sodium hyaluronate provided in the COMOD(r)
device seem to be equally efficient in alleviating OSD symptoms following
cataract extraction surgery and any of them should be routinely added to the
postoperative regime. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
https://clinicaltrials.gov/ct2/show/NCT02558218NCT02558218.
PMID- 28497072
TI - Improved MECP2 Gene Therapy Extends the Survival of MeCP2-Null Mice without
Apparent Toxicity after Intracisternal Delivery.
AB - Intravenous administration of adeno-associated virus serotype 9 (AAV9)/hMECP2 has
been shown to extend the lifespan of Mecp2-/y mice, but this delivery route
induces liver toxicity in wild-type (WT) mice. To reduce peripheral transgene
expression, we explored the safety and efficacy of AAV9/hMECP2 injected into the
cisterna magna (ICM). AAV9/hMECP2 (1 * 1012 viral genomes [vg]; ICM) extended
Mecp2-/y survival but aggravated hindlimb clasping and abnormal gait phenotypes.
In WT mice, 1 * 1012 vg of AAV9/hMECP2 induced clasping and abnormal gait. A
lower dose mitigated these adverse phenotypes but failed to extend survival of
Mecp2-/y mice. Thus, ICM delivery of this vector is impractical as a treatment
for Rett syndrome (RTT). To improve the safety of MeCP2 gene therapy, the gene
expression cassette was modified to include more endogenous regulatory elements
believed to modulate MeCP2 expression in vivo. In Mecp2-/y mice, ICM injection of
the modified vector extended lifespan and was well tolerated by the liver but did
not rescue RTT behavioral phenotypes. In WT mice, these same doses of the
modified vector had no adverse effects on survival or neurological phenotypes. In
summary, we identified limitations of the original vector and demonstrated that
an improved vector design extends Mecp2-/y survival, without apparent toxicity.
PMID- 28497073
TI - Integrase-Deficient Lentiviral Vector as an All-in-One Platform for Highly
Efficient CRISPR/Cas9-Mediated Gene Editing.
AB - The CRISPR/Cas9 systems have revolutionized the field of genome editing by
providing unprecedented control over gene sequences and gene expression in many
species, including humans. Lentiviral vectors (LVs) are one of the primary
delivery platforms for the CRISPR/Cas9 system due to their ability to accommodate
large DNA payloads and sustain robust expression in a wide range of dividing and
non-dividing cells. However, long-term expression of LV-delivered Cas9/guide RNA
may lead to undesirable off-target effects characterized by non-specific RNA-DNA
interactions and off-target DNA cleavages. Integrase-deficient lentiviral vectors
(IDLVs) present an attractive means for delivery of CRISPR/Cas9 components
because: (1) they are capable of transducing a broad range of cells and tissues,
(2) have superior packaging capacity compared to other vectors (e.g., adeno
associated viral vectors), and (3) they are expressed transiently and demonstrate
very weak integration capability. In this manuscript, we aimed to establish IDLVs
as a means for safe and efficient delivery of CRISPR/Cas9. To this end, we
developed an all-in-one vector cassette with increased production efficacy and
demonstrated that CRISPR/Cas9 delivered by the improved IDLV vectors can mediate
rapid and robust gene editing in human embryonic kidney (HEK293T) cells and post
mitotic brain neurons in vivo, via transient expression and with higher gene
targeting specificity than the corresponding integrase-competent vectors.
PMID- 28497074
TI - Efficient Production of Papillomavirus Gene Delivery Vectors in Defined In Vitro
Reactions.
AB - Papillomavirus capsids can package a wide variety of nonviral DNA plasmids and
deliver the packaged genetic material to cells, making them attractive candidates
for targeted gene delivery vehicles. However, the papillomavirus vectors
generated by current methods are unlikely to be suitable for clinical
applications. We have developed a chemically defined, cell-free, papillomavirus
based vector production system that allows the incorporation of purified plasmid
DNA (pseudogenome) into high-titer papillomavirus L1/L2 capsids. We investigated
the incorporation of several DNA forms into a variety of different papillomavirus
types, including human and animal types. Our results show that papillomavirus
capsids can package and transduce linear or circular DNA under defined
conditions. Packaging and transduction efficiencies were surprisingly variable
across capsid types, DNA forms, and assembly reaction conditions. The
pseudoviruses produced by these methods are sensitive to the same entry
inhibitors as cell-derived pseudovirions, including neutralizing antibodies and
heparin. The papillomavirus vector production systems developed in this study
generated as high as 1011 infectious units/mg of L1. The pseudoviruses were
infectious both in vitro and in vivo and should be compatible with good
manufacturing practice (GMP) requirements.
PMID- 28497075
TI - Development of a Novel AAV Gene Therapy Cassette with Improved Safety Features
and Efficacy in a Mouse Model of Rett Syndrome.
AB - Rett syndrome (RTT), caused by loss-of-function mutations in the MECP2 gene, is a
neurological disorder characterized by severe impairment of motor and cognitive
functions. The aim of this study was to investigate the impact of vector design,
dosage, and delivery route on the efficacy and safety of gene augmentation
therapy in mouse models of RTT. Our results show that AAV-mediated delivery of
MECP2 to Mecp2 null mice by systemic administration, and utilizing a minimal
endogenous promoter, was associated with a narrow therapeutic window and resulted
in liver toxicity at higher doses. Lower doses of this vector significantly
extended the survival of mice lacking MeCP2 or expressing a mutant T158M allele
but had no impact on RTT-like neurological phenotypes. Modifying vector design by
incorporating an extended Mecp2 promoter and additional regulatory 3' UTR
elements significantly reduced hepatic toxicity after systemic administration.
Moreover, direct cerebroventricular injection of this vector into neonatal Mecp2
null mice resulted in high brain transduction efficiency, increased survival and
body weight, and an amelioration of RTT-like phenotypes. Our results show that
controlling levels of MeCP2 expression in the liver is achievable through
modification of the expression cassette. However, it also highlights the
importance of achieving high brain transduction to impact the RTT-like
phenotypes.
PMID- 28497076
TI - Molecular Mechanism of beta-Catenin Signaling Pathway Inactivation in ETV1
Positive Prostate Cancers.
AB - In the United States of America, prostate cancer is the second most common age
related cancer among men. African-American men have the highest incidence of, and
mortality rate from this disease in the United States. According to the American
Cancer Society, 29% of all cancer cases and 9% of all cancer deaths are a result
of prostate cancer. Individuals who are at highest risk include African-American
men, men over 60 years of age, and those with a family history of the disease.
African-Americans also have twice the risk of developing prostate cancer as
compared to Caucasians. Erythroblastosis virus E26 transformation-specific (ETS)
factors play an important role in human cancers. ETS Variant 1 (ETV1), an ETS
factor, is notable for its association in prostate cancers, where truncated ETV1
(dETV1) or its full length counterpart is overexpressed in approximately 10% of
the prostate cancer patients. Prostate cancer tumorigenesis may be initiated by
deregulation of the Wnt/beta-catenin pathway. Mutations that stabilize beta
catenin were shown to contribute to the loss of cell-growth control in
tumorigenesis. We hypothesized that ETV1's interaction with components of the
Wnt/beta-catenin pathway may alter beta-catenin's interaction with downstream
tumor-suppressor genes, which are critical in regulating apoptosis and cell
growth properties of prostate cells. Our results demonstrate for the first time
that ETV1 alters beta-catenin activity by activating kinases that regulate
Wnt/beta-catenin activity through post-translational modification in prostate
cancer cells. We further demonstrate that therapeutic agents such as PD98059,
that reverse effect of ETV1 on Wnt/beta-catenin signaling pathway, can be used to
target ETV1-positive prostate cancer cells. These therapeutic agents could have a
profound impact on prevention and treatment of prostate cancer which may help to
reduce health disparity seen in minority patients. Understanding the role of ETV1
in Wnt/beta-catenin pathway will also allow us to develop better diagnostic
tools, which can be used as a biomarker for ETV1-positive prostate cancers.
PMID- 28497078
TI - Joubert syndrome; misleading presentation of two cases as pseudo-tumor cerebri
and literature review.
AB - Joubert syndrome is a rare autosomal recessive disorder that may have different
clinical presentation such as ataxia, hyperpnea, sleep apnea, nystagmus,
hypotonia, seizure and retinitis pigmentosa. We present a 22-year-old girl and
her older sibling, labeled as cerebral palsy. She had renal transplant years ago
without the true diagnosis of the disorder. Brain imaging revealed the classic
"molar tooth sign" appearance, and clinical evaluation established the diagnosis
for both of the siblings. Imaging should be done to evaluate the
neuroradiological findings of Joubert syndrome. With a neonate with Joubert
syndrome in a family, antenatal diagnosis by ultrasound is crucial for future
siblings.
PMID- 28497077
TI - What do we know about pediatric renal microlithiasis?
AB - Renal or calyceal microlithiasis is a common disorder with increasing prevalence
especially in infants and younger children. The main presenting symptoms and the
underlying metabolic abnormalities of renal microlithiasis are similar to renal
stone. Although renal microlithiasis is considered as a main problem of the
health system with diverse etiologies, our information about its natural course
is very limited. Hence, further investigations to make an appropriate clinical
approach to this entity is mandatory. Also, general practitioners, pediatricians,
nephrologists and urologists have to be well educated regarding renal
microlithiasis for early diagnosis, appropriate evaluation and proper management
of this entity. In this review study, we focused on collection of the present
information about different aspects of renal microlithiasis in children.
PMID- 28497079
TI - Spontaneous rupture of continent cutaneous urinary diversion after 25 years.
AB - Spontaneous rupture of a continent cutaneous urinary diversion is uncommon and
diagnosis of this situation requires a high degree of suspicion. In this paper we
present a 66-year-old man with continent cutaneous pouch after radical
cystoprostatectomy that presented with spontaneous perforation 25 years after
surgery. Spontaneous pouch perforation in our case after 25 years emphasizes the
need for long follow-up in patients with continent diversion.
PMID- 28497080
TI - Applying data mining techniques to determine important parameters in chronic
kidney disease and the relations of these parameters to each other.
AB - Introduction: Chronic kidney disease (CKD) includes a wide range of
pathophysiological processes which will be observed along with abnormal function
of kidneys and progressive decrease in glomerular filtration rate (GFR).
According to the definition decreasing GFR must have been present for at least
three months. CKD will eventually result in end-stage kidney disease. In this
process different factors play role and finding the relations between effective
parameters in this regard can help to prevent or slow progression of this
disease. There are always a lot of data being collected from the patients'
medical records. This huge array of data can be considered a valuable source for
analyzing, exploring and discovering information. Objectives: Using the data
mining techniques, the present study tries to specify the effective parameters
and also aims to determine their relations with each other in Iranian patients
with CKD. Material and Methods: The study population includes 31996 patients with
CKD. First, all of the data is registered in the database. Then data mining tools
were used to find the hidden rules and relationships between parameters in
collected data. Results: After data cleaning based on CRISP-DM (Cross Industry
Standard Process for Data Mining) methodology and running mining algorithms on
the data in the database the relationships between the effective parameters was
specified. Conclusion: This study was done using the data mining method
pertaining to the effective factors on patients with CKD.
PMID- 28497081
TI - Relationship between serum irisin, glycemic indices, and renal function in type 2
diabetic patients.
AB - Introduction: Irisin is a novel peptide that plays notable role in human and
animal biology and physiology. It has been reported that irisin may improve
insulin resistance and related disturbances. Objectives: The aim of this
investigation was to assess the relationship between serum irisin, glycemic
indices, and renal function in diabetic subjects. Patients and Methods: In this
cross-sectional study, a total of 102 type 2 diabetes mellitus (T2DM) patients
were recruited. Blood biochemical parameters, including fasting plasma sugar
(FBS), glycosylated hemoglobin (HbA1C), serum uric acid (sUA), creatinine
concentration and glomerular filtration rate (GFR) were measured. All statistical
analysis was performed with SPSS 16.0. Results: There was a positive correlation
between irisin and age (P=0.05, r=0.19) and a negative correlation between irisin
and body mass index (BMI) (P=0.01, r=-0.25) was detected. There was a significant
difference of serum irisin level between patients with normal and abnormal FBS
too. Conclusion: In this study we found, irisin concentration was increased with
age, decreased with BMI, and it was higher in subject with abnormal FBS. Thus
further research is needed to provide inclusive understanding of irisin
associated physiological effects and possible implications in clinical
conditions.
PMID- 28497082
TI - Evaluation of selenium on kidney function following ischemic injury in rats;
protective effects and antioxidant activity.
AB - Introduction: Renal dysfunction is caused by ischemia-reperfusion (I/R) injury,
which is a common problem in kidney surgery or kidney transplantation. The human
body consists of enormous complex antioxidant systems, which inquires adequate
selenium (Se) absorption for normal physiologic function. It is known that Se has
some antioxidant effects. Objectives: In the present research, effects of the Se
on damages caused by I/R injury investigated. Materials and Methods: In this
experimental research, four groups of rats (weighing 220+/-10 g) used, include
control group, I/R group, healthy group treated with Se for two weeks, and I/R
group with two-week Se treatment. On the test day, I/R was treated in both right
and left renal arteries for 45 minutes and the reperfusion was done for 24 hours.
Results: In I/R group, the amount of urea and serum creatinine (Cr) was an injury
indicator of the kidney cells which showed a significant increase compared with
the control group. When the treatment with Se significantly reduced these
indicators, glutathione (GSH) enzyme levels reduced significantly in the second
group and the enzyme levels increased due to Se treatment in the fourth group.
Furthermore, malondialdehyde (MDA) enzyme levels increased in I/R group due to
the Se treatment in the fourth group which was significantly reduced. In
addition, the tissue damage was reduced in the fourth group compared with I/R
group. Conclusion: Se has a protective effect against the I/R injury. This effect
might be due to the antioxidant properties of Se.
PMID- 28497083
TI - Impact of FGF23 level on calcium and phosphorus levels in post-renal
transplantation.
AB - Introduction: The level of fibroblast growth factor 23 (FGF23) may be considered
as a prognostic factor for assessing renal function in regulating components of
phosphate and vitamin D hemostasis. Objectives: The present study aimed to
evaluate the prognostic value of FGF23 level to predict renal function after
renal transplantation. Patients and Methods: Fifteen consecutive patients
scheduled for renal transplantation. To assess renal function status, the MDRD
formula and isotope scan were applied. The study endpoint was to assess the level
of FGF23 and other factors involving calcium and phosphorus metabolism before and
also 3 and 12 months after transplantation and also to determine role of FGF23 to
predict postoperative renal function. Results: The mean level of FGF23 was
839.51+/-694.56 rhog/mL at baseline that reduced to 44.31+/-22.01 rhog/mL and
20.13+/-36.50 rhog/mL, 3 and 12 months after initial assessment. The levels of
FGF23 was significantly lower at 3 and 12 months after baseline (P=0.01 and
P=0.02, respectively) with no difference in FGF23 level between the time points
of 3 and 12 months after transplantation. Baseline level of FGF23 was found to be
higher in the patients with higher glomerular filtration rate (GFR), in older
patients, in males, in those patients with diabetic nephropathy, in those with
acceptable renal function than in patients who suffered transplant rejection.
Conclusion: The level of postoperative FGF23 is an important marker for secretion
of phosphorus from kidneys emphasizing the central role of FGF23 marker to
regulate calcium and phosphorus metabolism after a successful renal
transplantation.
PMID- 28497084
TI - Effects of radiofrequency radiation in the presence of gold nanoparticles for the
treatment of renal cell carcinoma.
AB - Introduction: The most common type of kidney cancer is renal cell carcinoma
(RCC), which accounts for more than 80% of all kidney cancers. Objectives: The
aim of this study was to evaluate the effects of radiofrequency (RF) radiation in
the presence of gold nanoparticles (GNPs) for the treatment of RCC. Materials and
Methods: Human embryonic kidney (HEK) cancer cells were divided into 6 groups.
Various tests were performed on HEK cells in the presence of RF and GNPs. In
order to investigate the radiation effects on the cells' survival, MTT [3-(4,5
dimethylthiazol-2-yl)-2,5-iphenyltetrazolium bromide] assay was performed at
different days during and post-irradiation period. The repeated measure analysis
of variance (ANOVA) method was used for statistical analysis of the cells'
survival using SPSS version 16.0. A significant level of 0.05 was considered to
the tests. Results: Using the ANOVA test, a significant decrease in cell's
survival was seen in the RF exposed group 3 compared to the control group
(P=0.035). While, differences were not significant between RF exposed group 2 and
the control group (P>0.05). A significant decrease in cell's survival in the RF
exposed groups 5 (P=0.025) and 6 (P=0.018) at the presence of GNP compared to the
control group was seen. Conclusion: Results of this study showed that, this
method can be efficiently used for RCC treatment as an alternative to
nephrectomy. More follow up in vivo studies on mammalians are needed to
investigate the potential of the presented method for clinical applications.
PMID- 28497085
TI - Evaluation of water and electrolytes disorders in severe acute diarrhea patients
treated by WHO protocol in eight large hospitals in Tehran; a nephrology
viewpoint.
AB - Introduction: The most common cause of death from diarrhea is the shock caused by
dehydration, electrolytes and acid-base disorders. Objectives: The aim of this
study was to evaluate water and electrolytes disorders in diarrhea patients after
treating severe acute diarrhea. Patients and Methods: In this study we used a
historical cohort and studied patients who were hospitalized due to acute
diarrhea and were similarly treated for dehydration and water and electrolyte
disorders as recommended by the World Health Organization (WHO) guideline.
Electrolytes, pH, serum creatinine (Cr) level on admission and during treatment
were recorded. Patients with underlying diseases were excluded from the study.
Results: Of 121 patients who were enrolled in the study, 67.8% had hyponatremia
on admission (plasma Na <137 mEq/L) and 5.8% had hypernatremia. Around, 33.88% of
patients had hypokalemia and 2.4% had hyperkalemia. All hyperkalemia disorders
were treated, but 87.1% of patients had hypokalemia or low potassium levels, or
they were affected by uncorrected hypokalemia and were in need of further
measures. Of all, 56.75% had acidosis and 21% of patients with acidosis were not
treated or the severity of their acidosis increased during treatment. There was a
significant relationship between acute renal failure (ARF) and hypokalemia at the
time of admission (P<0.001), potassium loss during treatment (P<0.001), acidosis
(0.005), and cholera-related diarrhea (0.05). Conclusion: The high prevalence of
hypokalemia in these patients as well as potassium loss during treatment
indicates insufficient level of potassium in the therapeutic solutions. Mild
hyponatremia in most patients highlights the need for isotonic solutions to treat
dehydration.
PMID- 28497086
TI - The effect of vibration on the severity of restless legs syndrome in hemodialysis
patients.
AB - Introduction: The restless legs syndrome (RLS) is a neurological disorder in
patients undergoing hemodialysis. This syndrome causes individual's disturbed
rest, discomfort, and stress, and secondarily to weakened functioning and
disturbance in occupational activities and familial life. Objectives: The present
study aimed at investigate the effect of vibration on the severity of the
manifestation of symptoms of RLS in hemodialysis patients. Patients and Methods:
This is an interventional before-after study conducted on 80 patients with RLS in
hemodialysis wards of Yazd hospitals. The samples were selected randomly and
intervention was performed on the patients as vibration for 10 minutes three
times per week during 4 succeeding weeks. The questionnaire of severity of RLS
was completed before the study and at the last day of intervention before and
after vibration. The data were analyzed with SPSS 23 using descriptive statistics
and paired t test (P<0.05). Results: Our findings showed that most patients were
at the moderate level of severity of symptoms before (68.8%) and after (78.8%)
intervention and there was a significant difference in the mean score of RLS
between before (18.99) and after (12.82) intervention (P=0.001). Conclusion:
Based on the results of this study, it can be concluded that vibration decreases
the severity of symptoms of RLS in hemodialysis patients. Hence, it is
recommended that vibration be used as a cost-effective and safe procedure to
improve the symptoms of RLS in this group of patients.
PMID- 28497087
TI - Renal function in patients with diabetic foot infection; does antibiotherapy
affect it?
AB - Introduction: Antibiotic treatment (antibiotherapy) of diabetic foot ulcers has
been proven to have toxic effect on renal function. Objectives: This study aimed
to evaluate renal function in patients with diabetic foot infection. Patients and
Methods: This cross-sectional retrospective study was performed on 142 patients
with diabetic foot ulcers hospitalized in Shahid Yahyanejad hospital of Babol
during 2013. After referring to profile of the patients, they were assigned to
participate in two groups: group A consisted of patients receiving antibiotics
with a low risk renal toxicity and patients who received antibiotics with a
higher risk of renal toxicity were placed in group B. Glomerular filtration rate
(GFR) was measured and calculated based on serum concentration of creatinine and
Cockcroft-Gault equation. Data was analyzed using SPSS version 20.0 with chi
square, t test and paired t tests. Results: Group A consisted of 74 patients
(52.1%) and 68 patients (47.9%) participated in group B. GFRs before and after
antibiotherapy were 64.73+/-33.87 cc/min and 59.10+/-30.51 cc/min, respectively
(P=0.004). In group B, GFR decreased significantly after antibiotherapy
(P=0.002). Conclusion: According to the present study, renal function decreased
after antibiotherapy and in patients who received antibiotics with higher
nephrotoxicity rate, the rate of this decline was higher.
PMID- 28497088
TI - Pulmonary hypertension among patients undergoing hemodialysis.
AB - Introduction: The epidemiology of pulmonary hypertension (PHT) among long-term
hemodialysis patients has been described in relatively small studies in Iran.
Objectives: The purpose of this study was to evaluate the prevalence of PHT and
its relationship among end-stage renal disease (ESRD) patients undergoing long
term hemodialysis (HD). Patients and Methods: In a cross-sectional study,
patients with ESRD treated with HD for at least 3 months in the Imam hospital
enrolled for the study. PHT was defined as an estimated systolic pulmonary artery
pressure (PAP) equal to or higher than 25 mm Hg using echocardiograms performed
by cardiologist. Results: A total of 69 HD patients were included in the
investigation. The mean of age of our patients was 52.6+/-15.3 years. The mean
duration of HD was 39+/-36 months. The mean ejection fraction was 45+/-7%. The
prevalence of PHT was 62.3%. These patients were more likely to have lower
ejection fraction. The PHT was more common among female HD patients. We did not
find any association between PHT and cause of ESRD, duration of HD, anemia and
serum calcium, phosphor and parathyroid hormone levels. Conclusion: Our findings
show that PHT is a common problem among ESRD patients undergoing maintenance HD
and it is strongly associated with heart failure. It is necessary to screen this
disorder among these patients.
PMID- 28497089
TI - Impact of oral capsule of Peganum harmala on alleviating urinary symptoms in men
with benign prostatic hyperplasia; a randomized clinical trial.
AB - Introduction: Benign prostatic hyperplasia (BPH) is considered as a major cause
of lower urinary tract symptoms (LUTS) in older men and its most common sign is
nocturia. Objectives: This study aimed to determine the effect of the seeds of
Peganum harmala compared with tamsulosin on alleviating urinary symptoms in
patients with BPH. Patients and Methods: In this single blind clinical trial
study, 90 patients diagnosed with BPH and LUTS, based on international prostate
standard survey (IPSS) were divided into three groups. The first group was
received oral capsule of P. harmala, the second group was administered tamsulosin
with oral P. harmala seed and the third group was received tamsulosin drug and
they were evaluated after 4 weeks. Results: The results showed that the
difference between mean scores of IPSS was significant after the intervention
(P=0.001). Besides, the mean of IPSS in the three groups was significantly
different (P=0.001) (the first group 41.9+/-5.3, the second group 21.0+/-4.4 ,the
third group 16.5+/-3.7 respectively). However, after the intervention, patients
in the second group had the lowest average on most indicators of IPSS but the
difference was only significant about urinary frequency, nocturia and
intermittency(P<0.05). Conclusion: Application of Peganum harmala seed can be
useful in reducing urinary symptoms in patients with BPH.
PMID- 28497090
TI - Association between prostate specific antigen levels and coronary artery
angioplasty.
AB - Introduction: Prostate-specific antigen (PSA) is a protein, whose serum levels
changes during various physiologic and pathologic situations. Recently, the
relationship between PSA and cardiologic disorders has been assessed. Objectives:
The purpose of this study was to assess the association of percutaneous coronary
intervention (PCI) complications with PSA serum levels. Patients and Methods: In
this study, 100 eligible patients undergoing PCI were included. The total PSA
serum values were analyzed pre- and post-procedure. The association between PSA
levels with age, gender, inflammatory (C-reactive protein [CRP] and white blood
cell [WBC]), cardiogenic (troponin, CK-MB, echocardiography and angiography
results), and nephrology (creatinine) properties was investigated. Results:
Changes in the level of PSA pre- and post-PCI was not significant (P=0.2).
However, based on the pathology, patients with acute coronary syndrome (ACS) had
a significant difference in the levels of PSA compared to cases of stable
ischemic heart disease (SIHD) (P=0.008). Moreover, the effect of gender on the
changes in PSA level following PCI was conclusive. There was no association
between the direct effect of PCI parameters or PCI complications on PSA level
changes. Conclusion: The results showed that PSA levels were affected by the
etiology of cardiac disorders instead of therapeutic methods like PCI.
PMID- 28497091
TI - Restless leg syndrome in chronic hemodialysis patients in Mashhad hemodialysis
centers.
AB - Introduction: Restless leg syndrome (RLS) is a sensory motor disorder. Patients
with this syndrome have serious and uncontrollable desire to move their legs,
which is mostly due to an uncomfortable feeling intensified when they are
motionless. It may be a genetic disorder or secondary to iron deficiency,
neurodegenerations, pregnancy, some drugs and severe kidney diseases. Objectives:
This study was designed to find out the prevalence and its risk factors of RLS in
hemodialysis patients. Patients and Methods: This multicenter cross-sectional
study was done on 260 hemodialysis patients. The prevalence of RLS was measured
using International Restless Legs Syndrome Study Group (IRLSSG)'s RLS
Questionnaire (RLSQ). Potential risk factors for RLS including underlying cause
of chronic renal failure, duration on dialysis, biochemical tests, dialysis
adequacy, and erythropoietin and also venofer dosage in recent month and
demographic data were also evaluated. Results: The prevalence of RLS was 55%
including 59.4% males and 40.6% females. Their mean age of RLS patients and their
dialysis duration were significantly higher than other group (P<0.05). Their body
mass index (BMI) and serum calcium were significantly higher (P<0.05). However
erythropoietin dosage and serum hemoglobin level were lower in RLS patients
(P<0.05). Significant predictors of RLS were history of diabetes mellitus (DM),
hypertension (HTN), smoking (P<0.05). There was not significant relation between
RLS and dialysis adequacy, serum intact parathyroid hormone (iPTH), urea,
ferritin and venofer dosage (P>0.05). Conclusion: According to the results, RLS
is a common disorder in hemodialysis patients which can affect strongly on their
life. So particular attention and sooner diagnosis of RLS in high risk patients
for better management is necessary.
PMID- 28497092
TI - The relationship between dialysis adequacy and serum uric acid in dialysis
patients; a cross-sectional multi-center study in Iranian hemodialysis centers.
AB - Introduction: Uric acid is one of the most significant uremic toxins accumulating
in chronic renal failure patients treated with standard dialysis. Its clearance
has not any exact relation with urea and creatinine clearance. Objectives: The
aim of this study was to investigate the relationship between adequacy of
dialysis and serum level of uric acid in dialysis patients of some dialysis
centers in Iran. Patients and Methods: In this study 1271 hemodialysis patients
who have been treated for more than 3 months were evaluated. Their information
and examinations from their files in all over the country were gathered and
analyzed using SPSS versin18.0. Results: In this study, a significant
relationship between dialysis duration and serum level of uric acid was not
detected, however, a significant relationship between patients Kt/V and uric acid
(R=0.43, P=0.029) was seen. Patients who had higher adequacy of dialysis had a
higher level of plasma uric acid. Conclusion: For better controlling of plasma
uric acid level of hemodialysis patients, increasing of the adequacy of dialysis
or its duration is not effective. Other modalities of decreasing of serum uric
acid like, changing diet or lifestyle or medical therapy may be necessary.
PMID- 28497093
TI - Association between abnormal serum free light chains ratio and known prognostic
factors in lymphoma; a nephrology viewpoint.
AB - Introduction: The serum immunoglobulin free light chain (FLC) assay quantities of
free kappa (kappa) and lambda (lambda) light chains. This assay has prognostic
value in plasma cell proliferative disorders. There are limited data on serum FLC
in B-cell malignancies. Objectives: The aim of this study was to compare the
known prognostic factors in non-Hodgkin's lymphoma of the type B-cell and Hodgkin
disease with an abnormal secretion amount of light chains in these lymphomas.
Patients and Methods: The association of pretreatment FLC and FLC ratio
(kappa:lambda) with previously known prognostic factors for lymphoma such as the
international prognostic index (IPI) and B symptoms were evaluated in 50 patients
with Hodgkin's and non-Hodgkin's lymphoma. IPI is a prognostic score given based
on the clinical variables including age, disease stage, serum LDH and extra-nodal
involvement. Elevated FLC and an abnormal kappa:lambda ratio was defined based on
the previous publications. Results: The prevalence of abnormal FLC ratio was 38%
in all patients and 40.9% in patients with diffuse large B-cell lymphoma.
Abnormal FLC ratio was significantly associated with IPI (P=0.04) and B symptoms
(P=0.02) in both groups of the patients with Hodgkin's and non-Hodgkin's
lymphoma. The stage of the disease in Hodgkin's lymphoma patients showed a
significant relationship with the abnormal FLC ratio (P=0.04). Presence of the B
symptoms in patients with Hodgkin's lymphoma had a modest but not statistically
significant association with the abnormal FLC ratio (P=0.07). Conclusion:
Abnormal FLC ratio as a new potent prognostic biomarker has a significant
association with IPI which is the most common clinical tool used to predict
outcome in lymphoma patients. Since there is a need for developing a reliable and
quantitative prognostic biomarker for lymphoma, evaluation of the independent
effect of the abnormal serum FLC ratio is suggested to be considered in future
prospective studies. The result of these studies will also be useful for
nephrologists, while serum immunoglobulin FLC is capable to damage kidney.
PMID- 28497095
TI - Case Reports: Stories Worth Telling in Today's Bone and Joint Literature.
PMID- 28497094
TI - An update on diabetic kidney disease, oxidative stress and antioxidant agents.
AB - Diabetes mellitus is a metabolic disease that is defined by relative or absolute
deficiency of insulin secretion. Diabetic kidney disease seems to be one of the
most frequent complications of diabetes mellitus. Based on evidence, increased
free-radical formation and/or diminished antioxidant defenses induce oxidative
stress that is implicated in the pathogenesis of diabetic kidney disease. It is
evident that diabetic state induces oxidative stress through different signaling
pathways as well as reactive oxygen species (ROS) formation that attributes to
the activation of various downstream signaling cascade leading to structural the
way to structural and functional changes in kidney.
PMID- 28497096
TI - Patient Complaints Emphasize Non-Technical Aspects of Care at a Tertiary Referral
Hospital.
AB - BACKGROUND: Patient concerns represent opportunities for improvement in
orthopaedic care. This study's objective is to identify the nature and prevalence
of unsolicited patient complaints regarding orthopaedic care at a tertiary
referral hospital. The primary null hypothesis that there are no demographic
factors associated with complaint types was tested. Secondarily we determined if
the overall complaint number and types differed by year. METHODS: Complaints to
the hospital ombudsperson by orthopaedic patients between January 1997 and June
2013 were reviewed. All 1118 complaints were categorized: access and
availability, humaneness and disrespect, communication, expectations of care and
treatment, distrust, billing and research. RESULTS: Patients between 40 and 60
years of age filed the most complaints in all categories except distrust (more
common in patients over age 80) and research. Women were slightly more likely to
address access and availability, humaneness, disrespect, and billing compared to
men. The overall number of complaints peaked in 1999. The most common issue was
access and availability followed by communication, and humaneness/disrespect.
CONCLUSION: Half of concerns voiced by patients addressed interpersonal issues.
The largest category was related to access and availability. Quality improvement
efforts can address technology to improve access and availability as well as
empathy and communication strategies.
PMID- 28497097
TI - A Randomized Controlled Pilot Study of Educational Techniques in Teaching Basic
Arthroscopic Skills in a Low-income Country.
AB - BACKGROUND: Little is known about how to introduce complex technologies like
arthroscopy into low-income countries. Thus, we compared low- versus high
resource intensive methods of teaching basic arthroscopic skills in a randomized
controlled trial in Haiti. METHODS: Forty-eight Haitian orthopaedic surgeons and
residents attending an orthopaedic conference in Haiti were block randomized to
receive instruction through a composite video (Control) or a composite video plus
hands-on teaching with an expert visiting surgeon (Intervention). A low-fidelity
surgical simulator tested visualization and triangulation skills. Participants
completed a pre- and post-test where the goal was to sequentially tap the most
numbers in 2.5 minutes. Outcome metrics included highest tapped number, number of
errors, visualization loss, and number of lookdowns. Multivariate linear
regression was used to confirm randomization and compare outcomes between groups.
RESULTS: Seventy-five percent of initially randomized attendees participated with
similar attrition rates between both groups. All participants who performed a pre
test completed a post-test. In terms of highest tapped number, treatment and
control groups significantly improved compared to pre-test scores, with mean
improvement of 3.2% (P=0.007) and 2.2% (P=0.03), respectively. Improvement
between treatment and control groups was not statistically different (P=0.4). No
statistically significant change was seen with regard to other metrics.
CONCLUSION: We describe a protocol to introduce basic arthroscopic skills in a
low-income country using a low-resource intensive teaching method. However, this
method of learning may not be optimal given the failure to improve in all outcome
measures.
PMID- 28497098
TI - Gravity Reduction View: A Radiographic Technique for the Evaluation and
Management of Weber B Fibula Fractures.
AB - BACKGROUND: While various radiographic parameters and application of
manual/gravity stress have been proposed to elucidate instability for Weber B
fibula fractures, the prognostic capability of these modalities remains unclear.
Determination of anatomic positioning of the mortise is paramount. We propose a
radiographic technique, the Gravity Reduction View (GRV), which helps elucidate
non-anatomic positioning and reducibility of the mortise. METHODS: The patient is
positioned lateral decubitus with the injured leg elevated on a holder with the
fibula directed superiorly. The x-ray cassette is placed posterior to the heel,
with the beam angled at 15 degrees of internal rotation to obtain a mortise
view. Our proposed treatment algorithm is based upon the measurement of the
medial clear space (MCS) on the GRV versus the static mortise view (and in
comparison to the superior clear space (SCS)) and is based on reducibility of the
MCS. A retrospective review of patients evaluated utilizing the GRV was
performed. RESULTS: 26 patients with Weber B fibula fractures were managed
according to this treatment algorithm. Mean age was 50.57 years old (range:18-81,
SD=19). 17 patients underwent operative treatment and 9 patients were initially
treated nonoperatively. 2 patients demonstrated late displacement and were
treated surgically. Using this algorithm, at a mean follow-up of 26 weeks, all
patients had a final MCS that was less than the SCS (final mean MCS 2.86 mm vs.
mean SCS of 3.32) indicating effectiveness of the treatment algorithm.
CONCLUSIONS: The GRV is a radiographic view in which deltoid competency,
reducibility and initial positioning of the mortise are assessed by comparing a
static mortise view with the appearance of the mortise on the GRV. We have
proposed a treatment algorithm based on the GRV that we found it useful in our
patients in guiding treatment and achieving anatomic mortise alignment.
PMID- 28497099
TI - Acetabular Fractures in the Senior Population- Epidemiology, Mortality and
Treatments.
AB - BACKGROUND: Management of acetabular fractures in the senior population can be
one of the most challenging injuries to manage. Furthermore, treating surgeons
have a paucity of information to guide the treatment in this patient population.
THE PURPOSE OF THIS STUDY WAS TO DETERMINE: (1) demographic and epidemiologic
data, (2) mortality rates for nonoperative compared to operative management at
different time points, (3) common fracture configurations, and (4) fracture
fixation strategies in senior patients treated with acetabular fractures.
METHODS: Retrospective review of prospectively gathered data at a Level I trauma
center over a five-year period. 1123 acetabular fractures were identified. 156 of
them were for patients over the age of 65 (average age of 78). RESULTS: Falls and
motor vehicle accidents accounted for the two most common mechanisms of injury.
82% of patients had significant medical comorbidities. 51 patients (33%) died
within one year, in which 75% of them died within 90 days of their acetabular
fracture. 84% of the deceased patients, i.e. from the group of 51 patients, had
non-operative treatment. For patients treated with traction alone, there was a
79% one-year mortality and 50% mortality rate within 90 days. Within the entire
cohort, 70% had either an associated both-column (ABC) or anterior
column/posterior hemitransverse (AC/PHT) fracture pattern. Fifty-seven patients
(36.5%) underwent open reduction and internal fixation using standard reduction
techniques and surgical implants via two main surgical exposures of ilioinguinal
(69%) and Kocher-Langenbeck (29%). CONCLUSION: Geriatric patients with acetabular
fractures are uncommon accounting for only 14% of all acetabular fractures.
Patients who undergo surgery show lower mortality rates. ABC and AC/PHT fracture
patterns are the two most common fracture patterns. Routine fixation constructs
and implants can be used to manage these challenging fractures. Most patients are
unable to return to their homes and instead require skilled nursing facility
during their convalescence.
PMID- 28497100
TI - Does Tranexamic Acid Reduce Bleeding during Femoral Fracture Operation?
AB - BACKGROUND: Proximal Femoral shaft fractures are commonly associated with marked
blood loss which can lead to postoperative acute anemia and some other
complications. Tranexamic acid (TA) is an antifibrinolytic medication that
reduces intra-and postoperative blood loss and transfusion requirements during
some elective surgeries. The aim of this study is to evaluate the effect of
intravenous Tranexamic acid (TA) on intraoperative blood loss and a subsequent
need for transfusion in patients who were undergoing surgery for femoral shaft
fractures in trauma setting. METHODS: Thirty-eight ASA grade I-II patients
undergoing proximal femoral shaft fracture surgery with intra medullary nailing
were included in this double blind randomized controlled clinical trial. They
were allocated into two groups. Group I, the intervention group with eighteen
patients received 15 mg/kg (TA) via intravenous infusion before surgical
incision. Patients in the placebo group received an identical volume of normal
saline. Hemoglobin level was measured four hours before and after the surgeries.
Postoperative blood loss and hemoglobin change as well as transfusion rates and
volumes were compared between the two groups. RESULTS: Mean Percentage fall in
hemoglobin after surgery were 1.75+/-0.84 and 2.04+/-1.9 in the study and placebo
groups, respectively (P=0.570). Hemoglobin loss was higher in the placebo group.
Transfusion rates was lower in TA group (5.6%) compared to the placebo group
(30%) (P=0.06). No significant difference in The Allowable Blood Loss during the
surgery was found between the two groups (P=0.894). CONCLUSION: Preoperative
treatment with TA reduces postoperative blood loss and the need for blood
transfusion during traumatic femoral fracture operation.
PMID- 28497101
TI - Prognostic Factors Affecting the Results of Modified Thompson Quadricepsplasty
for the Treatment of Extension Contracture of the Knee.
AB - BACKGROUND: Knee extension contracture is a disabling complication after
fractures around the knee. In this study we aimed to study factors influencing
the outcomes of quadricepsplasty for the treatment of traumatic knee extension
contracture. We hypothesized that there is no factor influencing the final range
of knee motion. METHODS: In this retrospective study, we included 64 patients who
underwent modified Thompson quadricepsplasty between 2008 to 2011 with a mean
follow-up time of 36 months. RESULTS: The mean change in flexion was 66 degrees.
Using Judet criteria, results were excellent in 41 patients (64%), good in 15
(23%), fair in 4 (6%) and poor in 4 (6%). Preoperative arc of flexion, duration
of extension contracture, number of previous surgeries on the limb, and BMI of
the patients were independently influencing the final flexion. CONCLUSION:
Modified Thompson quadricepsplasty is associated with high number of excellent
and good results especially when it is performed earlier in more severe
contractures. Preoperative arc of flexion, interval between trauma surgery and
quadricepsplasty, the number of prior surgeries, and BMI influence the outcomes
of quadricepsplasty.
PMID- 28497102
TI - Use of Hardware Battery Drill in Orthopedic Surgery.
AB - Among the power drills (Electrical/Pneumatic/Battery) used in Orthopedic surgery,
battery drill has got several advantages. Surgeons in low resource settings could
not routinely use Orthopedic battery drills (OBD) due to the prohibitive cost of
good drills or poor quality of other drills. "Hardware" or Engineering battery
drill (HBD) is a viable alternative to OBD. HBD is easy to procure, rugged in
nature, easy to maintain, durable, easily serviceable and 70 to 75 times cheaper
than the standard high end OBD. We consider HBD as one of the cost effective
equipment in Orthopedic operation theatres.
PMID- 28497103
TI - Reverse Total Shoulder Arthroplasty for the Treatment of Synovial Chondromatosis:
A Case Report and Review of the Literature.
AB - Synovial chondromatosis affecting the glenohumeral joint is rare. Treatment
primarily consists of arthroscopic loose body removal and synovectomy. Shoulder
arthroplasty has been mentioned in the literature as a treatment option for
patients with coexisting arthritis, although the results have been underreported.
The case of an 84-year-old man with long standing synovial chondromatosis of the
shoulder resulting in severe degenerative disease is presented. The patient was
treated with a reverse total shoulder arthroplasty, loose body removal, and a
complete synovectomy. Three and six month follow up results have shown a decrease
in the visual analogue scale for pain, improved range of motion, and no
radiographic evidence of disease recurrence. Reverse total shoulder arthroplasty
is a viable treatment option for synovial chondromatosis in patients with
coexisting glenohumeral arthritis demonstrating good short term outcomes.
PMID- 28497104
TI - Stress Fracture of the Lateral Femoral Condyle after Total Knee Arthroplasty.
AB - BACKGROUND: This is to assess one of the rare complications after total knee
replacement and to assess risk factors of failure. METHODS: 11 patients with
varus knee and an average age of 67 years underwent TKA between 2005 and 2013.
All patients returned with a sudden sharp knee pain, disability to walk and
significant decrease in ROM about 4 to 8 weeks after surgery. Radiographic
examination revealed a lateral femoral condylar stress fracture. RESULTS: After
analyzing the images, we found common characteristics among all patients, which
might be attributable to the later fracture including varus deformity>25, femoral
component lateralization, and valgus correction. CONCLUSION: Surgeons should be
aware of the risk factors to consider before, during, and after surgery.
PMID- 28497105
TI - Challenges in Evaluating Sleep Disturbances in Patients with Hand and Upper
Extremity Disease.
PMID- 28497106
TI - Stress and Intimate Partner Aggression.
AB - Evidence suggests that stressed couples also tend to be aggressive couples.
Chronic external stresses interact with individuals' dispositional and regulatory
deficiencies, resulting in a spillover of these stresses into the relationship.
High individual stress in combination with problematic interaction styles and
problem-solving abilities increases the likelihood of IPA. We applied the I3
Model to better organize the instigating, impelling, and inhibiting factors and
processes that moderate the stress-IPA association. Evidence suggests that
certain forms of stress, such as IPA victimization, reliably instigate IPA
perpetration, with weak inhibitory processes and impaired problem solving
moderating the stress-IPA association. More research is needed that specifies the
'perfect storm' of factors that increase our understanding of how, and for whom,
stress increases IPA risk.
PMID- 28497107
TI - NGP 555, a gamma-Secretase Modulator, Lowers the Amyloid Biomarker, Abeta42, in
Cerebrospinal Fluid while Preventing Alzheimer's Disease Cognitive Decline in
Rodents.
AB - INTRODUCTION: Alzheimer's disease (AD) is defined by the progressive accumulation
of amyloid plaques and neurofibrillary tangles in the brain which precedes
cognitive decline by years. METHODS: Using amyloid biomarkers, chemical modeling,
mouse behavioral models, and drug development techniques we investigate the
properties of NGP 555, a clinical-stage gamma-secretase modulator. RESULTS: NGP
555 shifts amyloid peptide production to the smaller, non-aggregating forms of
amyloid. Our preclinical studies show beneficial effects on amyloid biomarkers,
pathology, and cognition. NGP 555 has successfully completed chemistry,
pharmacology, toxicity, metabolism, and safety studies. DISCUSSION: Abundant data
support Abeta42 as a target for prophylactic or early-stage intervention
therapies in AD. The gamma-secretase modulator, NGP 555 is being actively
developed in human clinical trials for the prevention of Alzheimer's disease with
the overall aim to achieve an appropriate balance of potency/efficacy on reducing
the toxic forms of amyloid versus safety.
PMID- 28497108
TI - A meta-analysis of endoscopic ultrasound-fine-needle aspiration compared to
endoscopic ultrasound-fine-needle biopsy: diagnostic yield and the value of
onsite cytopathological assessment.
AB - Background The diagnostic yield of endoscopic ultrasound (EUS) guided fine-needle
aspiration (FNA) is variable, and partly dependent upon rapid onsite evaluation
(ROSE) by a cytopathologist. Second generation fine-needle biopsy (FNB) needles
are being increasingly used to obtain core histological tissue samples. Aims
Studies comparing the diagnostic yield of EUS guided FNA versus FNB have reached
conflicting conclusions. We therefore conducted a systematic review and meta
analysis to compare the diagnostic yield of FNA with FNB, and specifically
evaluating the diagnostic value of ROSE while comparing the two types of needles.
Methods We searched several databases from inception to 10 April 2016 to identify
studies comparing diagnostic yield of second generation FNB needles with standard
FNA needles. Risk ratios (RR) were calculated for categorical outcomes of
interest (diagnostic adequacy, diagnostic accuracy, and optimal quality
histological cores obtained). Standard mean difference (SMD) was calculated for
continuous variables (number of passes required for diagnosis). These were pooled
using random effects model of meta-analysis to account for heterogeneity. Meta
regression was conducted to evaluate the effect of ROSE on various outcomes of
interest. Results Fifteen studies with a total of 1024 patients were included in
the analysis. We found no significant difference in diagnostic adequacy [RR 0.98
(0.91, 1.06), (I2 = 51 %)]. Although not statistically significant (P = 0.06), by
meta-regression, in the absence of ROSE, FNB showed a relatively better
diagnostic adequacy. For solid pancreatic lesions only, there was no difference
in diagnostic adequacy [RR 0.96 (0.86, 1.09), (I2 = 66 %)]. By meta-regression,
in the absence of ROSE, FNB was associated with better diagnostic adequacy (P =
0.02). There was no difference in diagnostic accuracy [RR 0.99 (0.95, 1.03), (I2
= 27 %)] or optimal quality core histological sample procurement [RR 0.97 (0.89,
1.05), (I2 = 9.6 %)]. However, FNB established diagnosis with fewer passes [SMD
0.93 (0.45, 1.42), (I2 = 84 %)]. The absence of ROSE was associated with a higher
SMD, i. e., in the presence of an onsite pathologist, FNA required relatively
fewer passes to establish the diagnosis than in the absence of an onsite
pathologist. Conclusions There is no significant difference in the diagnostic
yield between FNA and FNB, when FNA is accompanied by ROSE. However, in the
absence of ROSE, FNB is associated with a relatively better diagnostic adequacy
in solid pancreatic lesions. Also, FNB requires fewer passes to establish the
diagnosis.
PMID- 28497109
TI - Hippocampal TNFalpha Signaling Contributes to Seizure Generation in an Infection
Induced Mouse Model of Limbic Epilepsy.
AB - Central nervous system infection can induce epilepsy that is often refractory to
established antiseizure drugs. Previous studies in the Theiler's murine
encephalomyelitis virus (TMEV)-induced mouse model of limbic epilepsy have
demonstrated the importance of inflammation, especially that mediated by tumor
necrosis factor-alpha (TNFalpha), in the development of acute seizures. TNFalpha
modulates glutamate receptor trafficking via TNF receptor 1 (TNFR1) to cause
increased excitatory synaptic transmission. Therefore, we hypothesized that an
increase in TNFalpha signaling after TMEV infection might contribute to acute
seizures. We found a significant increase in both mRNA and protein levels of
TNFalpha and the protein expression ratio of TNF receptors (TNFR1:TNFR2) in the
hippocampus, a brain region most likely involved in seizure initiation, after
TMEV infection, which suggests that TNFalpha signaling, predominantly through
TNFR1, may contribute to limbic hyperexcitability. An increase in hippocampal
cell-surface glutamate receptor expression was also observed during acute
seizures. Although pharmacological inhibition of TNFR1-mediated signaling had no
effect on acute seizures, several lines of genetically modified animals deficient
in either TNFalpha or TNFRs had robust changes in seizure incidence and severity
after TMEV infection. TNFR2-/- mice were highly susceptible to developing acute
seizures, suggesting that TNFR2-mediated signaling may provide beneficial effects
during the acute seizure period. Taken together, the present results suggest that
inflammation in the hippocampus, caused predominantly by TNFalpha signaling,
contributes to hyperexcitability and acute seizures after TMEV infection.
Pharmacotherapies designed to suppress TNFR1-mediated or augment TNFR2-mediated
effects of TNFalpha may provide antiseizure and disease-modifying effects after
central nervous system infection.
PMID- 28497111
TI - Investigating the Influence of Biological Sex on the Behavioral and Neural Basis
of Face Recognition.
AB - There is interest in understanding the influence of biological factors, like sex,
on the organization of brain function. We investigated the influence of
biological sex on the behavioral and neural basis of face recognition in healthy,
young adults. In behavior, there were no sex differences on the male Cambridge
Face Memory Test (CFMT)+ or the female CFMT+ (that we created) and no own-gender
bias (OGB) in either group. We evaluated the functional topography of ventral
stream organization by measuring the magnitude and functional neural size of 16
individually defined face-, two object-, and two place-related regions
bilaterally. There were no sex differences in any of these measures of neural
function in any of the regions of interest (ROIs) or in group level comparisons.
These findings reveal that men and women have similar category-selective
topographic organization in the ventral visual pathway. Next, in a separate task,
we measured activation within the 16 face-processing ROIs specifically during
recognition of target male and female faces. There were no sex differences in the
magnitude of the neural responses in any face-processing region. Furthermore,
there was no OGB in the neural responses of either the male or female
participants. Our findings suggest that face recognition behavior, including the
OGB, is not inherently sexually dimorphic. Face recognition is an essential skill
for navigating human social interactions, which is reflected equally in the
behavior and neural architecture of men and women.
PMID- 28497110
TI - Accumbal Cholinergic Interneurons Differentially Influence Motivation Related to
Satiety Signaling.
AB - Satiety, rather than all or none, can instead be viewed as a cumulative decrease
in the drive to eat that develops over the course of a meal. The nucleus
accumbens (NAc) is known to play a critical role in this type of value
reappraisal, but the underlying circuits that influence such processes are
unclear. Although NAc cholinergic interneurons (CINs) comprise only a small
proportion of NAc neurons, their local impact on reward-based processes provides
a candidate cell population for investigating the neural underpinnings of
satiety. The present research therefore aimed to determine the role of NAc-CINs
in motivation for food reinforcers in relation to satiety signaling. Through
bidirectional control of CIN activity in mice, we show that when motivated by
food restriction, increasing CIN activity led to a reduction in palatable food
consumption while reducing CIN excitability enhanced food intake. These activity
dependent changes developed only late in the session and were unlikely to be
driven by the innate reinforcer strength, suggesting that CIN modulation was
instead impacting the cumulative change in motivation underlying satiety
signaling. We propose that on a circuit level, an overall increase in inhibitory
tone onto NAc output neurons played a role in the behavioral results, as
activating NAc-CINs led to an inhibition of medium spiny neurons that was
dependent on nicotinic receptor activation. Our results reveal an important role
for NAc-CINs in controlling motivation for food intake and additionally provide a
circuit-level framework for investigating the endogenous cholinergic circuits
that signal satiety.
PMID- 28497112
TI - FUNCTIONAL LIMITATION AND DEPRESSIVE SYMPTOMATOLOGY: CONSIDERING PERCEIVED STIGMA
AND DISCRIMINATION WITHIN A STRESS AND COPING FRAMEWORK.
AB - This study examines whether perceived stigma and discrimination moderate the
associations between functional limitation, psychosocial coping resources, and
depressive symptoms among people with physical disabilities. Using two waves of
data from a large community study including a representative sample of persons
with physical disabilities (N=417), an SEM-based moderated mediation analysis was
performed. Mediation tests demonstrate that mastery significantly mediates the
association between functional limitation and depressive symptoms over the study
period. Moderated mediation tests reveal that the linkage between functional
limitation and mastery varies as a function of perceived stigma and experiences
of major discrimination and day-to-day discrimination, however. The implications
of these findings are discussed in the context of the stress and coping
literature.
PMID- 28497113
TI - Toward a Cure: Does Host Immunity Play a Role?
AB - Three decades of research on human immunodeficiency virus (HIV) and AIDS reveal
that the human body has developed through evolution a genome immune system
embodying epigenetic regulation against pathogenic nucleic acid invasion. In HIV
infection, this epigenetic regulation plays a cardinal role in HIV RNA production
that silences HIV transcription at a molecular (RNA) level, controls viral load
at a cellular (biological) level, and governs the viremic stage of AIDS at the
clinical (patient) level. Even though the human genome is largely similar among
humans and HIV is a single viral species, human hosts show significant
differences in viral RNA levels, ranging from cell to organ to individual and
expressed as elite controllers, posttreatment controllers, and patients with
AIDS. These are signature biomarkers of typical epigenetic regulation whose
importance has been shunted aside by interpreting all of AIDS pathogenesis by the
known properties of innate and adaptive immunity. We propose that harnessing the
host genome immune system, defined as epigenetic immunity, against HIV infection
will lead toward a cure.
PMID- 28497114
TI - Selectable Markers for Use in Genetic Manipulation of Extensively Drug-Resistant
(XDR) Acinetobacter baumannii HUMC1.
AB - Acinetobacter baumannii is one of the most antibiotic-resistant pathogens in
clinical medicine, and extensively drug-resistant (XDR) strains are commonly
isolated from infected patients. Such XDR strains are already resistant to
traditional selectable genetic markers, limiting the ability to conduct
pathogenesis research by genetic disruption. Optimization of selectable markers
is therefore critical for the advancement of fundamental molecular biology
techniques to use in these strains. We screened 23 drugs that constitute a broad
array of antibiotics spanning multiple drug classes against HUMC1, a highly
virulent and XDR A. baumannii clinical blood and lung isolate. HUMC1 is resistant
to all clinically useful antibiotics that are reported by the clinical
microbiology laboratory, except for colistin. Ethical concerns about
intentionally establishing pan-resistance, including to the last-line agent,
colistin, in a clinical isolate made identification of other markers desirable.
We screened additional antibiotics that are in clinical use and those that are
useful only in a lab setting to identify selectable markers that were effective
at selecting for transformants in vitro. We show that supraphysiological levels
of tetracycline can overcome innate drug resistance displayed by this XDR strain.
Last, we demonstrate that transformation of the tetA (tetracycline resistance)
and Sh ble (zeocin resistance), but not pac (puromycin resistance), resistance
cassettes allow for selection of drug-resistant transformants. These results make
the genetic manipulation of XDR A. baumannii strains easily achieved. IMPORTANCE
Multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug
resistant (PDR) strains of Acinetobacter baumannii have frequently been
characterized. The ability of A. baumannii to develop resistance to antibiotics
is a key reason this organism has been difficult to study using genetic and
molecular biology approaches. Here we report selectable markers that are not only
useful but necessary for the selection of drug-resistant transformants in the
setting of drug-resistant backgrounds. Use of these selectable markers can be
applied to a variety of genetic and molecular techniques such as mutagenesis and
transformation. These selectable markers will help promote genetic and molecular
biology studies of otherwise onerous drug-resistant strains, while avoiding the
generation of pathogenic organisms that are resistant to clinically relevant
antibiotics.
PMID- 28497115
TI - An Efficient, Rapid, and Recyclable System for CRISPR-Mediated Genome Editing in
Candida albicans.
AB - Candida albicans is the most common fungal pathogen of humans. Historically,
molecular genetic analysis of this important pathogen has been hampered by the
lack of stable plasmids or meiotic cell division, limited selectable markers, and
inefficient methods for generating gene knockouts. The recent development of
clustered regularly interspaced short palindromic repeat(s) (CRISPR)-based tools
for use with C. albicans has opened the door to more efficient genome editing;
however, previously reported systems have specific limitations. We report the
development of an optimized CRISPR-based genome editing system for use with C.
albicans. Our system is highly efficient, does not require molecular cloning,
does not leave permanent markers in the genome, and supports rapid, precise
genome editing in C. albicans. We also demonstrate the utility of our system for
generating two independent homozygous gene knockouts in a single transformation
and present a method for generating homozygous wild-type gene addbacks at the
native locus. Furthermore, each step of our protocol is compatible with high
throughput strain engineering approaches, thus opening the door to the generation
of a complete C. albicans gene knockout library. IMPORTANCECandida albicans is
the major fungal pathogen of humans and is the subject of intense biomedical and
discovery research. Until recently, the pace of research in this field has been
hampered by the lack of efficient methods for genome editing. We report the
development of a highly efficient and flexible genome editing system for use with
C. albicans. This system improves upon previously published C. albicans CRISPR
systems and enables rapid, precise genome editing without the use of permanent
markers. This new tool kit promises to expedite the pace of research on this
important fungal pathogen.
PMID- 28497116
TI - pH-Mediated Microbial and Metabolic Interactions in Fecal Enrichment Cultures.
AB - pH and fermentable substrates impose selective pressures on gut microbial
communities and their metabolisms. We evaluated the relative contributions of pH,
alkalinity, and substrate on microbial community structure, metabolism, and
functional interactions using triplicate batch cultures started from fecal slurry
and incubated with an initial pH of 6.0, 6.5, or 6.9 and 10 mM glucose, fructose,
or cellobiose as the carbon substrate. We analyzed 16S rRNA gene sequences and
fermentation products. Microbial diversity was driven by both pH and substrate
type. Due to insufficient alkalinity, a drop in pH from 6.0 to ~4.5 clustered pH
6.0 cultures together and distant from pH 6.5 and 6.9 cultures, which experienced
only small pH drops. Cellobiose yielded more acidity than alkalinity due to the
amount of fermentable carbon, which moved cellobiose pH 6.5 cultures away from
other pH 6.5 cultures. The impact of pH on microbial community structure was
reflected by fermentative metabolism. Lactate accumulation occurred in pH 6.0
cultures, whereas propionate and acetate accumulations were observed in pH 6.5
and 6.9 cultures and independently from the type of substrate provided. Finally,
pH had an impact on the interactions between lactate-producing and -consuming
communities. Lactate-producing Streptococcus dominated pH 6.0 cultures, and
acetate- and propionate-producing Veillonella, Bacteroides, and Escherichia
dominated the cultures started at pH 6.5 and 6.9. Acid inhibition on lactate
consuming species led to lactate accumulation. Our results provide insights into
pH-derived changes in fermenting microbiota and metabolisms in the human gut.
IMPORTANCE The human gut is a dynamic environment in which microorganisms
consistently interact with the host via their metabolic products. Some of the
most important microbial metabolic products are fermentation products such as
short-chain fatty acids. Production of these fermentation products and the
prevalence of fermenting microbiota depend on pH, alkalinity, and available
dietary sugars, but details about their metabolic interactions are unknown. Here,
we show that, for in vitro conditions, pH was the strongest driver of microbial
community structure and function and microbial and metabolic interactions among
pH-sensitive fermentative species. The balance between bicarbonate alkalinity and
formation of fatty acids by fermentation determined the pH, which controlled
microbial community structure. Our results underscore the influence of pH balance
on microbial function in diverse microbial ecosystems such as the human gut.
PMID- 28497118
TI - Novel beta-Lactamase blaARL in Staphylococcus arlettae.
AB - Whole-genome sequencing of penicillin-resistant Staphylococcus arlettae strain
SAN1670 from bovine mastitis milk revealed a novel beta-lactamase operon
consisting of the beta-lactamase-encoding gene blaARL, the antirepressor-encoding
gene blaR1ARL, and the repressor-encoding gene blaIARL. The functionality of
blaARL was demonstrated by gene expression in Staphylococcus aureus. The blaARL
operon was chromosomally located in SAN1670 and present in 10 additional
unrelated strains, suggesting intrinsic penicillin resistance in S. arlettae.
Furthermore, a GenBank search revealed more unique potential beta-lactamases in
Staphylococcus species. IMPORTANCE Penicillins are an important group of
antibiotics used to treat various types of infections caused by Gram-positive
bacteria. So far, the blaZ gene was the only known beta-lactamase gene in
staphylococci. However, other putative beta-lactamases were identified, and one
of them was shown to be a novel functional beta-lactamase encoded by blaARL in
Staphylococcus arlettae, further limiting treatment options.
PMID- 28497117
TI - RNA Interference Restricts Rift Valley Fever Virus in Multiple Insect Systems.
AB - The emerging bunyavirus Rift Valley fever virus (RVFV) is transmitted to humans
and livestock by a large number of mosquito species. RNA interference (RNAi) has
been characterized as an important innate immune defense mechanism used by
mosquitoes to limit replication of positive-sense RNA flaviviruses and
togaviruses; however, little is known about its role against negative-strand RNA
viruses such as RVFV. We show that virus-specific small RNAs are produced in
infected mosquito cells, in Drosophila melanogaster cells, and, most importantly,
also in RVFV vector mosquitoes. By addressing the production of small RNAs in
adult Aedes sp. and Culex quinquefasciatus mosquitoes, we showed the presence of
virus-derived Piwi-interacting RNAs (piRNAs) not only in Aedes sp. but also in C.
quinquefasciatus mosquitoes, indicating that antiviral RNA interference in C.
quinquefasciatus mosquitoes is similar to the described activities of RNAi in
Aedes sp. mosquitoes. We also show that these have antiviral activity, since
silencing of RNAi pathway effectors enhances viral replication. Moreover, our
data suggest that RVFV does not encode a suppressor of RNAi. These findings point
toward a significant role of RNAi in the control of RVFV in mosquitoes.
IMPORTANCE Rift Valley fever virus (RVFV; Phlebovirus, Bunyaviridae) is an
emerging zoonotic mosquito-borne pathogen of high relevance for human and animal
health. Successful strategies of intervention in RVFV transmission by its
mosquito vectors and the prevention of human and veterinary disease rely on a
better understanding of the mechanisms that govern RVFV-vector interactions.
Despite its medical importance, little is known about the factors that govern
RVFV replication, dissemination, and transmission in the invertebrate host. Here
we studied the role of the antiviral RNA interference immune pathways in the
defense against RVFV in natural vector mosquitoes and mosquito cells and draw
comparisons to the model insect Drosophila melanogaster. We found that RVFV
infection induces both the exogenous small interfering RNA (siRNA) and piRNA
pathways, which contribute to the control of viral replication in insects.
Furthermore, we demonstrate the production of virus-derived piRNAs in Culex
quinquefasciatus mosquitoes. Understanding these pathways and the targets within
them offers the potential of the development of novel RVFV control measures in
vector-based strategies.
PMID- 28497119
TI - Aedes aegypti Piwi4 Is a Noncanonical PIWI Protein Involved in Antiviral
Responses.
AB - The small interfering RNA (siRNA) pathway is a major antiviral response in
mosquitoes; however, another RNA interference pathway, the PIWI-interacting RNA
(piRNA) pathway, has been suggested to be antiviral in mosquitoes. Piwi4 has been
reported to be a key mediator of this response in mosquitoes, but it is not
involved in the production of virus-specific piRNAs. Here, we show that Piwi4
associates with members of the antiviral exogenous siRNA pathway (Ago2 and Dcr2),
as well as with proteins of the piRNA pathway (Ago3, Piwi5, and Piwi6) in an
Aedes aegypti-derived cell line, Aag2. Analysis of small RNAs captured by Piwi4
revealed that it is predominantly associated with virus-specific siRNAs in
Semliki Forest virus-infected cells and, to a lesser extent, with viral piRNAs.
By using a Dcr2 knockout cell line, we showed directly that Ago2 lost its
antiviral activity, as it was no longer bound to siRNAs, but Piwi4 retained its
antiviral activity in the absence of the siRNA pathway. These results demonstrate
a complex interaction between the siRNA and piRNA pathways in A. aegypti and
identify Piwi4 as a noncanonical PIWI protein that interacts with members of the
siRNA and piRNA pathways, and its antiviral activities may be independent of
either pathway. IMPORTANCE Mosquitoes transmit several pathogenic viruses, for
example, the chikungunya and Zika viruses. In mosquito cells, virus replication
intermediates in the form of double-stranded RNA are cleaved by Dcr2 into 21
nucleotide-long siRNAs, which in turn are used by Ago2 to target the virus
genome. A different class of virus-derived small RNAs, PIWI-interacting RNAs
(piRNAs), have also been found in infected insect cells. These piRNAs are longer
and are produced in a Dcr2-independent manner. The only known antiviral protein
in the PIWI family is Piwi4, which is not involved in piRNA production. It is
associated with key proteins of the siRNA and piRNA pathways, although its
antiviral function is independent of their actions.
PMID- 28497120
TI - Analysis of Light- and Carbon-Specific Transcriptomes Implicates a Class of G
Protein-Coupled Receptors in Cellulose Sensing.
AB - In fungi, most metabolic processes are subject to regulation by light.
Trichoderma reesei is adapted to degradation of plant cell walls and regulates
production of the required enzymes in a manner dependent on the nutrient source
and the light status. Here we investigated the interrelated relevance of two
regulation levels of the transcriptome of T. reesei: light regulation and carbon
source-dependent control. We show that the carbon source (cellulose, lactose,
sophorose, glucose, or glycerol) is the major source of variation, with light
having a modulating effect on transcript regulation. A total of 907 genes were
regulated under cellulase-inducing conditions in light, and 947 genes were
regulated in darkness, with 530 genes overlapping (1,324 in total). Only 218 of
the 1,324 induction-specific genes were independent of light and not regulated by
the BLR1, BLR2, and ENV1 photoreceptors. Analysis of the genomic distribution of
genes regulated by light upon growth on cellulose revealed considerable overlap
of light-regulated clusters with induction-specific clusters and carbohydrate
active enzyme (CAZyme) clusters. Further, we found evidence for the operation of
a sensing mechanism for solid cellulosic substrates, with regulation of genes
such as swo1, cip1, and cip2 or of genes encoding hydrophobins which is related
to the cyclic AMP (cAMP)-dependent regulatory output of ENV1. We identified class
XIII G-protein-coupled receptors (GPCRs) CSG1 and CSG2 in T. reesei as putative
cellulose/glucose-sensing GPCRs. Our data indicate that the cellulase regulation
pathway is bipartite, comprising a section corresponding to transcriptional
regulation and one corresponding to posttranscriptional regulation, with the two
connected by the function of CSG1. IMPORTANCE In fungi, most metabolic processes
are subject to regulation by light. For Trichoderma reesei, light-dependent
regulation of cellulase gene expression is specifically shown. Therefore, we
intended to unravel the relationship between regulation of enzymes by the carbon
source and regulation of enzymes by light. Our two-dimensional analysis included
inducing and repressing carbon sources which we used to compare light-specific
regulation to dark-specific regulation and to rule out effects specific for a
single carbon source. We found close connections with respect to gene regulation
as well as significant differences in dealing with carbon in the environment in
light and darkness. Moreover, our analyses showed an intricate regulation
mechanism for substrate degradation potentially involving surface sensing and
provide a basis for knowledge-based screening for strain improvement.
PMID- 28497121
TI - Implementation of Isavuconazole in a Fluorescence-Based High-Performance Liquid
Chromatography Kit Allowing Simultaneous Detection of All Four Currently Licensed
Mold-Active Triazoles.
AB - Isavuconazole (ISZ) is a newly available broad-spectrum triazole agent recently
approved for the treatment of both invasive aspergillosis and mucormycosis. The
aim of this study was to develop a simple and reliable method for therapeutic
drug monitoring (TDM) of ISZ in human plasma samples. The method involves using a
kit from ChromSystems intended for TDM of itraconazole (ITZ), posaconazole (PSZ),
and voriconazole (VRZ) in serum/plasma for sample preparation and high
performance liquid chromatography, using fluorescence detection with emission and
excitation wavelengths set to 261 and 366 nm, respectively. The assay was linear
over the ISZ concentration range of 0.2 to 20.0 mg/liter, using a 0.1-ml sample
volume. The inter- and intraday coefficients of variation were all below 3.7%,
whereas the accuracies ranged from 95.0 to 106.2% and the mean extraction
recovery was 91.9%. In addition, the method worked well using four different
Vacutainer types, with six different healthy volunteers and under a number of
relevant storage conditions. Finally, the ISZ detection could be seamlessly
implemented in the TDM kit for VRZ, PSZ, and ITZ, enabling simultaneous detection
of all four triazoles. This method proved to be simple, accurate, precise, and
well suited for routine analysis work. It has been implemented in our laboratory
for the simultaneous quantitative analysis of ISZ, VRZ, PSZ, and ITZ for TDM and
pharmacokinetic research. IMPORTANCE Isavuconazole is a new broad-spectrum
triazole agent recently approved for the treatment of both invasive aspergillosis
and mucormycosis. Currently, there is no consensus regarding the potential need
for TDM of isavuconazole, and no therapeutic window has been defined. However, at
the ECIL-6 meeting in 2015, it was advised that TDM is indicated in a number of
different settings. In this study, we describe a rapid and validated isocratic
HPLC method for fluorescence-based detection and quantification of isavuconazole
in human plasma/serum samples. The method is simple and efficient with good
accuracy and precision and importantly only requires a small volume of patient
plasma/serum. Furthermore, this method is highly sensitive and selective and can
be detected simultaneously with the three other triazoles, itraconazole,
voriconazole, and posaconazole, without the need for expensive mass spectrometry
equipment.
PMID- 28497122
TI - The Microbiome-Mitochondrion Connection: Common Ancestries, Common Mechanisms,
Common Goals.
AB - Lynn Margulis in the 1960s elegantly proposed a shared phylogenetic history
between bacteria and mitochondria; this relationship has since become a
cornerstone of modern cellular biology. Yet, an interesting facet of the
interaction between the microbiome and mitochondria has been mostly ignored, that
of the systems biology relationship that underpins host health and longevity. The
mitochondria are descendants of primordial aerobic pleomorphic bacteria (likely
genus Rickettsia) that entered (literally and functionally) into a mutualistic
partnership with ancient anaerobic microbes (likely Archaea). A stable symbiosis
was established, given the metabolic versatility of the early mitochondria, which
were capable of providing energy with or without oxygen, whereas nutrient
gathering was the assumed responsibility of the host. While microbial
relationships with single-cell protists must have occurred in the past, as they
occur today, the evolution of multicellular organisms generated a new framework
for symbiosis with the microbial world, taking the ancient partnership to an
entirely new level. Cell-cell communication between microbes and single-cell
protists was augmented through multicellularity to allow distant communication
between the host cells and the microbiome, resulting in the development of
complex metabolic relationships and an immune system to manage these
interactions. Thus, the host is now the body and its resident mitochondria, and
the microbiome is an essential supplier of metabolites that act at the level of
mitochondria in skeletal muscle to stabilize host metabolism. We humans are
caretakers of a profoundly vast and diverse microbiota, the majority of which
resides in the gut. Indeed, the microbial genetic diversity of our microbiota
outstrips our own by several orders of magnitude, and the cellular abundance is
roughly equivalent to our somatic selves. Modern clinical science has elegantly
highlighted the importance of the microbiome for metabolic health and well-being.
This perspective underscores one fundamental facet of this symbiosis, the
ancestral mitochondrion-microbiome axis.
PMID- 28497123
TI - Functional trait diversity maximizes ecosystem multifunctionality.
AB - Understanding the relationship between biodiversity and ecosystem functioning has
been a core ecological research topic over the last decades. Although a key
hypothesis is that the diversity of functional traits determines ecosystem
functioning, we do not know how much trait diversity is needed to maintain
multiple ecosystem functions simultaneously (multifunctionality). Here, we
uncovered a scaling relationship between the abundance distribution of two key
plant functional traits (specific leaf area, maximum plant height) and
multifunctionality in 124 dryland plant communities spread over all continents
except Antarctica. For each trait, we found a strong empirical relationship
between the skewness and the kurtosis of the trait distributions that cannot be
explained by chance. This relationship predicted a strikingly high trait
diversity within dryland plant communities, which was associated with a local
maximization of multifunctionality. Skewness and kurtosis had a much stronger
impact on multifunctionality than other important multifunctionality drivers such
as species richness and aridity. The scaling relationship identified here
quantifies how much trait diversity is required to maximize multifunctionality
locally. Trait distributions can be used to predict the functional consequences
of biodiversity loss in terrestrial ecosystems.
PMID- 28497124
TI - PARV4 prevalence, phylogeny, immunology and coinfection with HIV, HBV and HCV in
a multicentre African cohort.
AB - Background: The seroprevalence of human parvovirus-4 (PARV4) varies considerably
by region. In sub-Saharan Africa, seroprevalence is high in the general
population, but little is known about the transmission routes or the prevalence
of coinfection with blood-borne viruses, HBV, HCV and HIV. Methods: To further
explore the characteristics of PARV4 in this setting, with a particular focus on
the prevalence and significance of coinfection, we screened a cohort of 695
individuals recruited from Durban and Kimberley (South Africa) and Gaborone
(Botswana) for PARV4 IgG and DNA, as well as documenting HIV, HBV and HCV status.
Results: Within these cohorts, 69% of subjects were HIV-positive. We identified
no cases of HCV by PCR, but 7.4% were positive for HBsAg. PARV4 IgG was positive
in 42%; seroprevalence was higher in adults (69%) compared to children (21%)
(p<0.0001) and in HIV-positive (52%) compared to HIV-negative individuals (24%)
(p<0.0001), but there was no association with HBsAg status. We developed an on
line tool to allow visualization of coinfection data
(https://purl.oclc.org/coinfection-viz). We identified five subjects who were PCR
positive for PARV4 genotype-3. Ex vivo CD8+ T cell responses spanned the entire
PARV4 proteome and we propose a novel HLA-B*57:03-restricted epitope within the
NS protein. Conclusions: This characterisation of PARV4 infection provides
enhanced insights into the epidemiology of infection and co-infection in African
cohorts, and provides the foundations for planning further focused studies to
elucidate transmission pathways, immune responses, and the clinical significance
of this organism.
PMID- 28497125
TI - Mapping ubiquitination sites of S. cerevisiae Mcm10.
AB - Minichromosome maintenance protein (Mcm) 10 is a part of the eukaryotic
replication machinery and highly conserved throughout evolution. As a multivalent
DNA scaffold, Mcm10 coordinates the action of proteins that are indispensable for
lagging strand synthesis, such as the replication clamp, proliferating cell
nuclear antigen (PCNA). The binding between Mcm10 and PCNA serves an essential
function during DNA elongation and is mediated by the ubiquitination of Mcm10.
Here we map lysine 372 as the primary attachment site for ubiquitin on S.
cerevisiae Mcm10. Moreover, we identify five additional lysines that can be
ubiquitinated. Mutation of lysine 372 to arginine ablates ubiquitination of
overexpressed protein and causes sensitivity to the replication inhibitor
hydroxyurea in cells that are S-phase checkpoint compromised. Together, these
findings reveal the high selectivity of the ubiquitination machinery that targets
Mcm10 and that ubiquitination has a role in suppressing replication stress.
PMID- 28497126
TI - Vulnerability to Depression in Youth: Advances from Affective Neuroscience.
AB - Vulnerability models of depression posit that individual differences in trait
like vulnerabilities emerge early in life and increase risk for the later
development of depression. In this review, we summarize advances from affective
neuroscience using neural measures to assess vulnerabilities in youth at high
risk for depression due to parental history of depression or temperament style,
as well as prospective designs evaluating the predictive validity of these
vulnerabilities for symptoms and diagnoses of depression across development.
Evidence from multiple levels of analysis indicates that healthy youth at high
risk for depression exhibit abnormalities in components of the Research Domain
Criteria (RDoC) positive valence systems, including blunted activation in the
striatum during reward anticipation and feedback, and that some of these measures
can be used to predict later symptoms. In addition, alterations in components of
RDoC's negative valence systems, including neural processing of sadness, loss,
and threat, have been observed in risk for depression, though effects appear to
be more task and method dependent. Within the social processes domain,
preliminary evidence indicates that neural processing of social feedback,
including heightened reactivity to exclusion and blunted response to social
reward, may be related to depression vulnerability. These studies indicate that
affective neuroscience can inform understanding of developmental pathways to
depression and identify altered emotional processing among youth at high risk. We
provide an integrated summary of consistent findings from this literature, along
with recommendations for future directions and implications for early
intervention.
PMID- 28497127
TI - Evidence of Glycolysis Up-Regulation and Pyruvate Mitochondrial Oxidation
Mismatch During Mechanical Unloading of the Failing Human Heart: Implications for
Cardiac Reloading and Conditioning.
AB - This study sought to investigate the effects of mechanical unloading on
myocardial energetics and the metabolic perturbation of heart failure (HF) in an
effort to identify potential new therapeutic targets that could enhance the
unloading-induced cardiac recovery. The authors prospectively examined paired
human myocardial tissue procured from 31 advanced HF patients at left ventricular
assist device (LVAD) implant and at heart transplant plus tissue from 11 normal
donors. They identified increased post-LVAD glycolytic metabolites without a
coordinate increase in early, tricarboxylic acid (TCA) cycle intermediates. The
increased pyruvate was not directed toward the mitochondria and the TCA cycle for
complete oxidation, but instead, was mainly converted to cytosolic lactate.
Increased nucleotide concentrations were present, potentially indicating
increased flux through the pentose phosphate pathway. Evaluation of mitochondrial
function and structure revealed a lack of post-LVAD improvement in mitochondrial
oxidative functional capacity, mitochondrial volume density, and deoxyribonucleic
acid content. Finally, post-LVAD unloading, amino acid levels were found to be
increased and could represent a compensatory mechanism and an alternative energy
source that could fuel the TCA cycle by anaplerosis. In summary, the authors
report evidence that LVAD unloading induces glycolysis in concert with pyruvate
mitochondrial oxidation mismatch, most likely as a result of persistent
mitochondrial dysfunction. These findings suggest that interventions known to
improve mitochondrial biogenesis, structure, and function, such as controlled
cardiac reloading and conditioning, warrant further investigation to enhance
unloading-induced reverse remodeling and cardiac recovery.
PMID- 28497128
TI - Innovative Therapeutics: Designer Natriuretic Peptides.
AB - Endogenous natriuretic peptides serve as potent activators of particulate
guanylyl cyclase receptors and the second messenger cGMP. Natriuretic peptides
are essential in maintenance of volume homeostasis, and can be of myocardial,
renal and endothelial origin. Advances in peptide engineering have permitted the
ability to pursue highly innovative drug discovery strategies. This has resulted
in designer natriuretic peptides that go beyond native peptides in efficacy,
specificity, and resistance to enzymatic degradation. Together with recent
improvements in peptide delivery systems, which have improved bioavailability,
further advances in this field have been made. Therefore, designer natriuretic
peptides with pleotropic actions together with strategies of chronic delivery
have provided an unparalleled opportunity for the treatment of cardiovascular
disease. In this review, we report the conceptual framework of peptide
engineering of the natriuretic peptides that resulted in designer peptides for
cardiovascular disease. We specifically provide an update on those currently in
clinical trials for heart failure and hypertension, which include Cenderitide,
ANX042 and ZD100.
PMID- 28497129
TI - Molecular modeling of the AhR structure and interactions can shed light on ligand
dependent activation and transformation mechanisms.
AB - Molecular modeling has given important contributions to elucidation of the main
stages in the AhR signal transduction pathway. Despite the lack of experimentally
determined structures of the AhR functional domains, information derived from
homologous systems has been exploited for modeling their structure and
interactions. Homology models of the AhR PASB domain have provided information on
the binding cavity and contributed to elucidate species-specific differences in
ligand binding. Molecular Docking simulations of the ligand binding process have
given insights into differences in binding of diverse agonists, antagonists, and
selective AhR modulators, and their application to virtual screening of large
databases of compounds have allowed identification of novel AhR ligands. Recently
available structural information on protein-protein and protein-DNA complexes of
other bHLH-PAS systems has opened the way for modeling the AhR:ARNT dimer
structure and investigating the mechanisms of AhR transformation and DNA binding.
Future research directions should include simulation of the protein dynamics to
obtain a more reliable description of intermolecular interactions involved in
signal transmission.
PMID- 28497131
TI - Guest Editorial: Implementation science for oral health promotion.
PMID- 28497130
TI - Not all that glitters is gold: A guide to critical appraisal of animal drug
trials in epilepsy.
AB - Preclinical studies have produced numerous drugs with antiseizure properties
which currently are the standard of care in clinical care. A third of the human
population with epilepsy still continues having seizures despite the ongoing
discoveries. The recognized clinical gaps of care that need to be addressed are
the identification of antiepileptogenic and disease modifying treatments,
treatments for refractory seizures or for seizures and epilepsies with limited or
unsatisfactory treatments, such as early life epileptic encephalopathies. In this
invited review, we provide a historical summary of the international efforts to
re-evaluate the strategies adopted in preclinical epilepsy therapy discovery
studies. We discuss issues that may impact the quality, interpretation and
validation of preclinical studies and their translation to successful therapies
for humans affected with epilepsy. These include the selection of animal models
and the study design, research practices that affect rigor, such as appropriate
use of statistics and reporting of study methods and results, their validation
across models, labs and preclinical-clinical studies, the need to harmonize
research methods and outcome assessment, and the importance to improve
translation to clinically appropriate situations. The epilepsy research community
is incrementally adopting collaborative research, including consortia or
multicenter studies to meet these needs. Improving the infrastructure that can
support these efforts will be instrumental in the future success.
PMID- 28497132
TI - Three generations of zirconia: ?From veneered to monolithic. Part II.
AB - This article presents the historical development of the different generations of
zirconia and their range of indications, from veneered to monolithic zirconia
restorations. While Part I concentrated on detailed information about the
development of zirconia for dental use and the mechanical and optical properties,
Part II deals with the resulting guidelines for working with the relevant
generations by summarizing the correct cementation procedure. Furthermore, this
part also focuses on translucency measurements for better characterization and
understanding of the different materials. The results obtained from measuring
light transmission and contrast ratio are compared and discussed in detail, with
the aid of clinical photographs. Finally, the reader is given practice-relevant
recommendations for different areas of clinical use of the zirconia generations
along with advice on how to process them appropriately.
PMID- 28497133
TI - Development and testing of satisfaction questionnaires for patients with
removable dental prostheses.
AB - OBJECTIVE: To develop and test self-administered satisfaction questionnaires for
patients with removable dental prostheses (RDPs) in the German language. METHOD
AND MATERIALS: A three-phase methodology was used. A pilot questionnaire was
developed in phase one. At the end of phase two, the final version of the
questionnaires were reached. In phase three, 192 questionnaires were distributed
to evaluate the psychometric properties of the final version of the
questionnaires. Construct validity, content validity from the patients'
perspective, and questionnaire reliability were estimated. RESULTS: At the end of
phase two, the final versions of the questionnaires were defined as instruments
with good face validity. At the end of phase three, content validity from the
patients' perspective was assessed and found to be good. Exploratory factor
analysis identified a one-factor model for each questionnaire. Consequently, each
questionnaire was summed to create a single index. Internal consistency of the
indexes was assessed using Cronbach's alpha and found to be excellent (alpha >
0.9). A high repeatability of all the items was identified through a test-retest.
Intra-class correlation coefficient (ICC) values ranged from 0.80 to 0.99.
CONCLUSION: The questionnaires and indexes are valid and highly reliable
instruments, and can be used to measure patient satisfaction with RDPs.
PMID- 28497134
TI - Enhanced planar perovskite solar cells with efficiency exceeding 16% via reducing
the oxygen vacancy defect state in titanium oxide electrode.
AB - In this work, the influence of oxygen vacancy defect (OVD) in compact titanium
oxide (c-TiO2) on the performance of planar perovskite solar cells (p-PSCs) is
investigated, and the possible mechanisms are also proposed. To meet our
objective, anatase c-TiO2 thin films with various OVD concentrations are prepared
by changing the oxygen flux during the DC magnetron sputtering process and are
characterized by the intensity of defect signals in the X-ray photoelectron
spectra. We conclude that abundant OVDs can trigger an obviously increased
majority carrier accumulation zone at the metal oxide/perovskite interface and
enhanced capacitance, thereby greatly deteriorating photogenerated carrier
collection efficiency. A detailed analysis of the study results also reveals that
the presence of OVD in the bulk and surface of c-TiO2 can slow down electronic
carrier transport and lower its electron quasi-Fermi level under illumination,
leading to the detrimental charge recombination in p-PSCs. Furthermore, we report
a remarkably enhanced p-PSC efficiency via preparing c-TiO2 using high oxygen
flux and subsequent ultraviolet ozone treatment. As a consequence, repeatable
power conversion efficiency (PCE) is propelled to as high as 16.62%, coupled with
negligible hysteresis and increased stability. These results provide a
significant implication for further perfecting efficient and stable p-PSCs for
their record efficiency.
PMID- 28497135
TI - Unscrambling micro-solvation of -COOH and -NH groups in neat dimethyl sulfoxide:
insights from 1H-NMR spectroscopy and computational studies.
AB - Dimethyl sulfoxide (DMSO) has a significant, multi-faceted role in medicine,
pharmacy, and biology as well as in biophysical chemistry and catalysis. Its
physical properties and impact on biomolecular structures still attract major
scientific interest, especially the interactions of DMSO with biomolecular
functional groups. In the present study, we shed light on the "isolated"
carboxylic (-COOH) and amide (-NH) interactions in neat DMSO via1H NMR studies
along with extensive theoretical approaches, i.e. molecular dynamics (MD)
simulations, density functional theory (DFT), and ab initio calculations, applied
on model compounds (i.e. acetic and benzoic acid, ethyl acetamidocyanoacetate).
Both experimental and theoretical results show excellent agreement, thereby
permitting the calculation of the association constants between the studied
compounds and DMSO molecules. Our coupled MD simulations, DFT and ab initio
calculations, and NMR spectroscopy results indicated that complex formation is
entropically driven and DMSO molecules undergo multiple strong interactions with
the studied molecules, particularly with the -COOH groups. The combined
experimental and theoretical techniques unraveled the interactions of DMSO with
the most abundant functional groups of peptides (i.e. peptide bonds, side chain
and terminal carboxyl groups) in high detail, providing significant insights on
the underlying thermodynamics driving these interactions. Moreover, the developed
methodology for the analysis of the simulation results could serve as a template
for future thermodynamic and kinetic studies of similar systems.
PMID- 28497136
TI - Local chemical potential, local hardness, and dual descriptors in temperature
dependent chemical reactivity theory.
AB - In this work we establish a new temperature dependent procedure within the grand
canonical ensemble, to avoid the Dirac delta function exhibited by some of the
second order chemical reactivity descriptors based on density functional theory,
at a temperature of 0 K. Through the definition of a local chemical potential
designed to integrate to the global temperature dependent electronic chemical
potential, the local chemical hardness is expressed in terms of the derivative of
this local chemical potential with respect to the average number of electrons.
For the three-ground-states ensemble model, this local hardness contains a term
that is equal to the one intuitively proposed by Meneses, Tiznado, Contreras and
Fuentealba, which integrates to the global hardness given by the difference in
the first ionization potential, I, and the electron affinity, A, at any
temperature. However, in the present approach one finds an additional temperature
dependent term that introduces changes at the local level and integrates to zero.
Additionally, a tau-hard dual descriptor and a tau-soft dual descriptor given in
terms of the product of the global hardness and the global softness multiplied by
the dual descriptor, respectively, are derived. Since all these reactivity
indices are given by expressions composed of terms that correspond to products of
the global properties multiplied by the electrophilic or nucleophilic Fukui
functions, they may be useful for studying and comparing equivalent sites in
different chemical environments.
PMID- 28497137
TI - Identification of two novel antioxidant peptides from edible bird's nest
(Aerodramus fuciphagus) protein hydrolysates.
AB - Edible bird's nest (EBN) is widely consumed as a delicacy and traditional
medicine amongst the Chinese. In the present study, for the first time, the
antioxidant properties of an EBN pepsin-trypsin hydrolysate of the swiftlet
species Aerodramus fuciphagus and its ultrafiltration fractions were
investigated. Thirteen peptides with molecular weights between 514.29 and 954.52
Da were identified in the EBN fraction with the use of mass spectrometry. Two
novel pentapeptides Pro-Phe-His-Pro-Tyr and Leu-Leu-Gly-Asp-Pro, corresponding to
f134-138 and f164-168 of cytochrome b of A. fuciphagus, indicated the highest
ORAC values of 14.95 and 14.32 MUM of TE MUM-1 peptide, respectively. Both
purified peptides showed resistance against simulated gastrointestinal proteases.
In addition, both peptides had no in vitro cytotoxicity on human lung MRC-5 cells
and prevented human liver carcinoma HepG2 cellular damage caused by hydroxyl
radicals. Therefore, it is suggested that EBN protein hydrolysates are a good
source of natural antioxidants and could be applied as nutraceutical compounds.
PMID- 28497138
TI - A Ni2P modified Ti4+ doped Fe2O3 photoanode for efficient solar water oxidation
by promoting hole injection.
AB - Nickel phosphide (Ni2P) was used as an excellent water oxidation cocatalyst for
photoelectrochemical (PEC) water splitting, which could significantly promote the
hole injection efficiency and suppress the back reaction of water oxidation over
a Ti4+ doped Fe2O3 photoanode.
PMID- 28497139
TI - LiMCO3 (M = K, Rb, Cs): a series of mixed alkali carbonates with large
birefringence.
AB - By the hydrothermal method, two new mixed alkali carbonates, LiRbCO3 and LiCsCO3
were synthesized for the first time. Both compounds crystallize in the monoclinic
space group P21/n, and exhibit similar wave like [LiCO3]infinity layers connected
by Rb-O and Cs-O bonds, respectively. They not only possess low melt temperature
and wide spectral transmittance range, but also have relatively large
birefringence confirmed by first principles calculations. In the mixed alkali
carbonates system of LiMCO3 (M = K, Rb, Cs), with the increase of atomic radius
of the alkali metal, the birefringence is reduced from 0.11 in LiKCO3 to 0.09 in
LiCsCO3, while the refractivity is increasing. The increasing refractivity and
decreasing birefringence can be interpreted by the enhancement of orbital
hybridization resulting from the reduced C-O bond length and weakened structural
anisotropy, respectively.
PMID- 28497140
TI - Critical behavior in tetragonal antiperovskite GeNFe3 with a frustrated
ferromagnetic state.
AB - Tetragonal GeNFe3 has a second-order ferromagnetic (FM) to paramagnetic
transition at 76 K. Our integrated investigations indicate that the ground FM
state is frustrated and the tetragonal symmetry is retained below 550 K based on
the results of variable temperature X-ray diffraction. Critical behavior was
analyzed by a systematic bulk magnetization study. The estimated critical
exponents by three different methods (modified Arrott plot, the Kouvel-Fisher
method, and critical isotherm analysis) conformably suggest that long-range
magnetic coupling described by mean-field (MF) theoretical model is dominant in
GeNFe3. The experimental M-T-H data collapse into two independent branches
according to the scaling equations m = f+/-(h) with the renormalized
magnetization m = epsilon-betaM(H, epsilon) and the magnetic field h = Hepsilon
(beta+gamma). The exchange distance is estimated as J(r) ~ r-4.8 on the basis of
the beta and gamma values, which lies between the long-range MF model (r-4.5) and
the short-range 3D Heisenberg (3DH) model (r-5). Our results indicate that the
competition between local magnetic moments of iron 3d electronic state and
itinerant covalent interactions of N-Fe bonds should be responsible for critical
behavior in this system.
PMID- 28497141
TI - Hierarchical bicontinuous structure of redox-active organic composites and their
enhanced electrochemical properties.
AB - The hierarchical bicontinuous structure of redox-active organic composites of
crystalline quinone derivatives and conductive polymers was generated through
simultaneous etching of the crystal and polymerization of the monomer. The
bicontinuous composite showed enhanced electrochemical properties as a result of
the smooth redox reaction of its components.
PMID- 28497142
TI - Methyl-functionalized MoS2 nanosheets with reduced lattice breathing for enhanced
pseudocapacitive sodium storage.
AB - Sodium ion batteries (SIBs) possess the potential to realize low-cost and large
scale energy storage due to the abundance of sodium. However, the large ionic
radius of sodium often leads to sluggish kinetics and large volume change,
limiting the further development of SIBs. Layered MoS2, with a large interlayer
distance, is a promising intercalation anode material for SIBs. In this work, we
report the synthesis of methyl-functionalized MoS2 (M-MoS2) nanosheets through a
facile second solvothermal method. During the second solvothermal treatment, the
pristine MoS2 is mostly converted from the 2H to 1T phase and the interlayer
distance is expanded from 0.65 to 0.80 nm. When evaluated as the anode for SIBs,
the M-MoS2 exhibits superior cycling stability and rate capability. Kinetic
analysis shows that the capacity is mainly contributed from a pseudocapacitive
process. Ex situ XRD shows that the M-MoS2 exhibits inhibited lattice breathing
and thus reduced volume change during cycling. This work demonstrates that the M
MoS2 is a promising candidate for pseudocapacitive sodium storage.
PMID- 28497143
TI - 18F-Fluoroform: a 18F-trifluoromethylating agent for the synthesis of SCF218F
aromatic derivatives.
AB - Herein the synthesis of various SCF218F-containing derivatives is reported by a
transition metal-free process. By using HCF218F, readily generated from a bench
stable difluoromethyl sulfonium salt, various aromatic disulfides were easily
converted into the desired radiolabelled trifluoromethylthiolated compounds in
the presence of a base. This protocol allowed the formation of the SCF218F
containing aromatic derivatives in good to excellent radiochemical yields. This
process was also extended to the corresponding selenium derivative.
PMID- 28497144
TI - Colloidal synthesis of urchin-like Fe doped NiSe2 for efficient oxygen evolution.
AB - The search for highly efficient non-precious metal electrocatalysts toward the
oxygen evolution reaction (OER) is extremely essential for renewable energy
systems. Here, we report the colloidal synthesis of Fe doped NiSe2, which
functions as a high-performance electrocatalyst for the OER in alkaline solution.
The NiFeSe catalysts are composed of urchin-like dendrites with a high number of
active sites, which could provide fast transportation of electrons and
electrolytes, and facile release of the evolved O2 bubbles during the OER
catalysis. Benefitting from this unique urchin-like structure and strong electron
interaction between Fe, Ni, and Se, the Ni1.12Fe0.49Se2 catalyst exhibits
excellent electrocatalytic activity and high durability toward the OER in
alkaline solution, with an overpotential of 227 mV at a current density of 10 mA
cm-2, which is, to the best of our knowledge, higher than most of the reported
selenide-based electrocatalysts.
PMID- 28497145
TI - A dendritic core-shell Cu@PtCu alloy electrocatalyst resulting in an enhanced
electron transfer ability and boosted surface active sites for an improved
methanol oxidation reaction.
AB - We reported the design of a core-shell Cu@PtCu electrocatalyst consisting of
dendritic PtCu alloy branches assembling on Cu core nanocrystals. The Cu@PtCu
electrocatalyst shows superior electrocatalytic performance toward a methanol
oxidation reaction. Its specific activity and mass activity can reach 3.56 mA cm
2 and 1568 mA mgPt-1, which are 4.8 and 7.1 times higher than those of a
commercial 20% Pt/C catalyst.
PMID- 28497147
TI - Relativistic effects in metallocorroles: comparison of molybdenum and tungsten
biscorroles.
AB - The homoleptic sandwich compounds - Mo and W biscorroles - have afforded a novel
platform for experimental studies of relativistic effects. A 200 mV difference in
reduction potential and a remarkable 130 nm shift of a near-IR spectral feature
have been identified as manifestations of relativistic effects on the properties
of these complexes.
PMID- 28497148
TI - Efficient synthesis of cyclic P-stereogenic phosphinamides from acyclic chiral
precursors via radical oxidative intramolecular aryl C-H phosphinamidation.
AB - We present a highly efficient method for the synthesis of cyclic P-stereogenic
phosphinamides via the Ce(IV)-promoted radical oxidative aryl C-H
phosphinamidation of acyclic P-stereogenic phosphinamides. The new protocol
provides a useful platform for the versatile synthesis of various potentially
useful P-stereogenic compounds.
PMID- 28497146
TI - The effect of the buffer solution on the adsorption and stability of horse heart
myoglobin on commercial mesoporous titanium dioxide: a matter of the right
choice.
AB - Despite the numerous studies on the adsorption of different proteins onto
mesoporous titanium dioxide and indications on the important role of buffer
solutions in bioactivity, a systematic study on the impact of the buffer on the
protein incorporation into porous substrates is still lacking. We here studied
the interaction between a commercial mesoporous TiO2 and three of the most used
buffers for protein incorporation, i.e. HEPES, Tris and phosphate buffer. In
addition, this paper analyzes the adsorption of horse heart myoglobin (hhMb) onto
commercial mesoporous TiO2 as a model system to test the influence of buffers on
the protein incorporation behavior in mesoporous TiO2. N2 sorption analysis, FT
IR and TGA/DTG measurements were used to evaluate the interaction between the
buffers and the TiO2 surface, and the effect of such an interaction on hhMb
adsorption. Cyclic voltammetry (CV) and electron paramagnetic resonance (EPR)
were used to detect changes in the microenvironment surrounding the heme. The
three buffers show a completely different interaction with the TiO2 surface,
which drastically affects the adsorption of myoglobin as well as its structure
and electrochemical activity. Therefore, special attention is required while
choosing the buffer medium to avoid misguided evaluation of protein adsorption on
mesoporous TiO2.
PMID- 28497149
TI - A convenient and clean synthetic method for borasiloxanes by Pd-catalysed
reaction of silanols with diborons.
AB - Selective O-borylation of silanols with diborons took place in the presence of Pd
catalysts to give the corresponding boryl silyl ethers in high yields.
PMID- 28497151
TI - Oxygen diffusion in ceria doped with rare-earth elements.
AB - We examine the effects of the dopant type and the dopant distribution on the ion
diffusion in ceria doped with rare-earth elements (Pr, Nd, Pm, Sm, Eu, and Gd).
Diffusion is simulated by means of a Kinetic Monte Carlo method using input
transition rates derived from diffusion barriers calculated in the framework of
density functional theory (DFT). Based on diffusion simulations, we discuss the
characteristics of the dopants in terms of the diffusion barriers, and study
oxygen ion trajectories for different dopants and distributions. Our simulations
show a trend of increasing ion diffusivity with increasing atomic number for all
distributions.
PMID- 28497150
TI - A near-room-temperature organic-inorganic hybrid ferroelectric:
[C6H5CH2CH2NH3]2[CdI4].
AB - An organic-inorganic hybrid compound, [C6H5CH2CH2NH3]2[CdI4], exhibits a
reversible ferroelectric phase transition at 301/297 K. Switchable dielectric
constant, second harmonic generation, and pyroelectricity were synchronously
observed accompanied by the order-disorder phase transition. This finding
promotes research on molecular ferroelectrics to search for promising
multifunctional switching materials at near room temperature.
PMID- 28497153
TI - Catalytic dehydrogenative dual functionalization of ethers: dealkylation
oxidation-bromination accompanied by C-O bond cleavage via aerobic oxidation of
bromide.
AB - Catalytic dehydrogenative dual functionalization (DDF) of ethers via oxidation,
dealkylation, and alpha-bromination by the aerobic oxidation of bromide was
developed to obtain the corresponding alpha-bromo ketones in high yields. In
particular, the reaction of substituted tetrahydrofurans as cyclic ethers
provided 3,3-dibromo tetrahydrofuran-2-ols in high yields selectively through the
double alpha-bromination.
PMID- 28497152
TI - The sedoheptulose 7-phosphate cyclases and their emerging roles in biology and
ecology.
AB - Covering up to: 1999-2016This highlight covers a family of enzymes of growing
importance, the sedoheptulose 7-phosphate cyclases, initially of interest due to
their involvement in the biosynthesis of pharmaceutically relevant secondary
metabolites. More recently, these enzymes have been found throughout Prokarya and
Eukarya, suggesting their broad potential biological roles in nature.
PMID- 28497154
TI - Hot off the press.
AB - A personal selection of 32 recent papers is presented covering various aspects of
current developments in bioorganic chemistry and novel natural products such as
macrophilone A from Macrorhynchia philippina.
PMID- 28497155
TI - Influence of washing and quenching in profiling the metabolome of adherent
mammalian cells: a case study with the metastatic breast cancer cell line MDA-MB
231.
AB - Metabolome characterisation is a powerful tool in oncology. To obtain a valid
description of the intracellular metabolome, two of the preparatory steps are
crucial, namely washing and quenching. Washing must effectively remove the
extracellular media components and quenching should stop the metabolic activities
within the cell, without altering the membrane integrity of the cell. Therefore,
it is important to evaluate the efficiency of the washing and quenching solvents.
In this study, we employed two previously optimised protocols for simultaneous
quenching and extraction, and investigated the effects of a number of washing
steps/solvents and quenching solvent additives, on metabolite leakage from the
adherent metastatic breast cancer cell line MDA-MB-231. We explored five washing
protocols and five quenching protocols (including a control for each), and
assessed for effectiveness by detecting ATP in the medium and cell morphology
changes through scanning electron microscopy (SEM) analyses. Furthermore, we
studied the overall recovery of eleven different metabolite classes using the GC
MS technique and compared the results with those obtained from the ATP assay and
SEM analysis. Our data demonstrate that a single washing step with PBS and
quenching with 60% methanol supplemented with 70 mM HEPES (-50 degrees C)
results in minimum leakage of intracellular metabolites. Little or no
interference of PBS (used in washing) and methanol/HEPES (used in quenching) on
the subsequent GC-MS analysis step was noted. Together, these findings provide
for the first time a systematic study into the washing and quenching steps of the
metabolomics workflow for studying adherent mammalian cells, which we believe
will improve reliability in the application of metabolomics technology to study
adherent mammalian cell metabolism.
PMID- 28497157
TI - Concentration-dependent circularly polarized luminescence (CPL) of chiral N,N'
dipyrenyldiamines: sign-inverted CPL switching between monomer and excimer
regions under retention of the monomer emission for photoluminescence.
AB - Herein, an unprecedented switching of circularly polarized luminescence (CPL) is
described for chiral 4,6-bis(1-(pyren-1-ylamino)propyl)dibenzo[b,d]furan (1). The
CPL band of chiral diamine 1, which contains two pyrene rings, can be switched
between the monomer and excimer emission regions under concomitant inversion of
the handedness, simply by changing the concentration of the fluorophore. In
contrast, the maximum photoluminescence (PL) intensity is always observed in the
monomer region, regardless of the concentration. The reversal of the intensity
ratio of monomer and excimer emission between PL and CPL was attributed to a
stronger CPL (|gem| = ~3-4 * 10-3) contribution from the minor excimer component,
which should exhibit an efficient chiral environment around the dimeric pyrenes.
PMID- 28497156
TI - Tumor suppressors microRNA-302d and microRNA-16 inhibit human glioblastoma
multiforme by targeting NF-kappaB and FGF2.
AB - Glioblastoma multiforme (GBM) is a highly malignant cancer in the brain with a
median survival time of approximately one year. However, the mechanisms
underlying GBM development and occurrence are poorly understood. Recently, miRNAs
were reported to play important roles in GBM. We performed microRNA profiling by
comparing the human GBM cell line T98G and control cell line HCN1A. MicroRNA
assays, PCR and Western blot analysis were performed to detect the expressions of
microRNAs, mRNAs and proteins of target genes, respectively. Cell migration and
invasion assays were conducted. A murine in situ xenograft tumor model was used
to evaluate tumor growth in vivo. Glioblastoma tissues were examined to
investigate the clinical relevance of our findings. MiR-302d and miR-16 levels
were found to be decreased in T98G cells. MiR-302d and miR-16 inhibited the
expressions of p65 and FGF2, respectively, by binding to the 3'-UTR of their
mRNAs. Over-expression of miR-302d and miR-16 inhibited T98G cell migration and
invasion in vitro, and tumorigenesis in the xenograft tumor mouse model in vivo,
by suppressing p65 and FGF2. Negative correlations between miR-302d and p65 and
between miR-16 and FGF2 were observed in patient glioblastoma tissues. MiR-302d
and miR-16 inhibit tumorigenesis by down-regulating p65 and FGF2, which
potentially contributes to the treatment of glioblastoma with clinical relevance.
PMID- 28497158
TI - Intralesional interleukin-2 for unresectable mucosal melanoma refractory to
nivolumab.
PMID- 28497159
TI - Current status of chimeric antigen receptor engineered T cell-based and immune
checkpoint blockade-based cancer immunotherapies.
AB - Adoptive cell therapies with chimeric antigen receptor (CAR) engineered T cells
(CAR-T) and immune checkpoint inhibition (ICI)-based cancer immunotherapies have
lately shown remarkable success in certain tumor types. CAR-T cell-based
therapies targeting CD19 can now induce durable remissions as well as prolong
disease-free survival of patients with CD19 positive treatment refractory B cell
malignancies and ICI-based therapies with humanized monoclonal antibodies against
the T cell inhibitory receptors CTLA-4 and PD-1 as well as against the PD-1
ligand, PD-L1, can now achieve durable remissions as well as prolongation of life
of a sizeable fraction of patients with melanoma and Hodgkin's lymphoma and non
small cell cancers. Most importantly, these immuno-therapeutic treatment
modalities have raised the possibility of achieving long-term "containment" as
well as "cures" for certain types of cancer. While this represents major advances
in cancer immunotherapy, both modalities come with considerable toxicities,
including fatalities. Although more work will be needed to bring CAR-T cell-based
therapies to the bedside for most major cancers and a good deal more will be
needed to make ICI-alone or in combination with other treatment modalities-work
more consistently and across most major cancers, these two treatment modalities
stand out as superb examples of successful translation of bench research to the
bedside as well as represent real progress in the field of cancer immunotherapy.
PMID- 28497160
TI - Spinal osteoid osteoma: efficacy and safety of radiofrequency ablation.
AB - OBJECTIVE: The aim of this study was to evaluate the efficacy and complications
of CT-guided radiofrequency ablation (RFA) of spinal osteoid osteoma (OO).
MATERIALS AND METHODS: Between 2002 and 2012, a total of 61 patients (46 male and
15 female, mean age 26.4 +/- 12.7 years) were subjected to RFA for spinal OO. The
diagnosis of OO was made after a period of pain and symptoms of 20.6 +/- 14.4
months. RFA was performed under conscious sedation and local analgesia. Clinical
symptoms were evaluated at 3, 6, and12 months, and at the end of the time of the
present investigation. Mean follow-up was 41.5 +/- 7.1 months. RESULTS: The
primary efficacy of RFA, complete regression of symptoms, was obtained in 57 out
of 61 patients (93.4%). Four out of 61 (6.5%) patients showed a relapse of OO
(after 3 months); 2 out of 4 were subjected to a second RFA, the remaining ones
were subjected to surgery. There was one complication (case of lower limb
paresthesia for 30 days after the ablation) and one possible complication (a disc
herniation). CONCLUSION: CT-guided RFA is an excellent treatment for spinal OO.
Our data suggest that this procedure should be considered for the first stage of
therapy for this disease.
PMID- 28497161
TI - Outcomes in diabetic foot ulcer patients with isolated T2 marrow signal
abnormality in the underlying bone: should the diagnosis of "osteitis" be changed
to "early osteomyelitis"?
AB - OBJECTIVE: To evaluate the variability of clinical treatment and outcomes based
on reporting of diabetic foot ulcer MRI findings of adjacent marrow T2
hyperintensity with normal T1 signal. MATERIALS AND METHODS: A retrospective
review was conducted of 46 MRI examinations evaluating diabetic foot ulcers that
demonstrated normal T1 marrow signal, but T2 marrow hyperintensity deep to the
ulcer. The cohort was divided based on MRI report impressions into three groups;
"osteitis without osteomyelitis" (OW), "osteitis but cannot exclude early
osteomyelitis" (OCEO) and "early osteomyelitis" (EO). Patient demographics (age,
gender) and accessory MRI findings of ulcer and sinus tract depth were recorded.
Initial clinical assessment and medical treatment (route and duration of
antibiotics), healing versus disease progression and histology or microbiology
results were recorded. RESULTS: The isolated marrow T2 signal hyperintensity was
reported as OW in 12 patients, OCEO in 18, and EO in 16. No statistical
difference in clinical assessment was demonstrated between the OW, OCEO, and EO
groups. Pathological condition was available in 15 patients within 0-7 days (mean
2.4 days) of the MRI examination, with 14 (93%) of these positive for
osteomyelitis by histopathology or positive cultures. Initial diagnosis of or
progression to osteomyelitis was shown in 28 patients (61%). CONCLUSION:
Treatment of suspected osteomyelitis is heavily determined by clinical factors.
Patients who initially demonstrate only T2 marrow signal abnormality under a
diabetic ulcer are eventually diagnosed as osteomyelitis in 61% of cases and
deserve aggressive treatment as early osteomyelitis when meeting clinical
parameters.
PMID- 28497162
TI - Cadaver embalming fluid for surgical training courses: modified Larssen solution.
AB - PURPOSE: 10% Formalin (F10)-fixed cadavers have disadvantages such as disturbing
smell, mucosal irritation, discoloration and rigidity. We aimed to determine a
suitable, simple and cost-effective embalming method that preserves color,
texture, pliability and flexibility of the tissues for a long time without a
disturbing smell and mucosal irritation. The embalmed cadavers were expected to
be durable against environmental effects, utilizable for multiple and repetitive
surgical trainings and instrumentations. METHODS: Eight male (six intact, two
autopsied bodies) and four female (three intact and one imported trunk) human
cadavers were preserved with modified Larssen solution (MLS). Preserved bodies
were kept in the deep freezers at -18/-20 degrees C. Bodies were allowed to thaw
at room temperature 3 days prior to use. They were used in postgraduate hands-on
courses for several medical disciplines. Each course lasted at least 1 day and
during this period the bodies were stayed at room temperature. Assessments of 30
trainers and 252 trainees were collected during the courses. Additionally, the
organoleptic characteristics of the fresh frozen (FF), preserved with MLS and F10
fixed cadavers were compared. RESULTS: The colors of muscles, fasciae, fatty
tissue, nerves and vessels were evaluated and life-like tissues of MLS cadavers
were impressive. There were no obvious or disturbing smell and sign of
putrefaction of the MLS cadavers. CONCLUSIONS: MLS is a sustainable and
relatively affordable soft cadaver embalming method. Its application is same as
in other conventional methods and does not need new equipment. This article
indicates the success of the MLS method in human cadavers.
PMID- 28497163
TI - [Alternative approaches in thyroid surgery].
AB - In thyroid surgery multiple different cervical minimally invasive (partly
endoscopically assisted) and extracervical endoscopic (partly robot-assisted)
approaches have been developed in the last 20 years. The aim of all these
alternative approaches to the thyroid gland is optimization of the cosmetic
result. The indications for the use of alternative and conventional approaches
are principally the same. Important requirements for the use of alternative
methods are nevertheless a broad experience in conventional thyroid operations of
the thyroid and adequate patient selection under consideration of the size of the
thyroid and the underlying pathology. Contraindications for the use of
alternative approaches are a large size of the thyroid gland including local
symptoms, advanced carcinomas, reoperations and previous radiations of the
anterior neck. The current article gives an overview of the clinically
implemented alternative approaches for thyroid surgery. Of those the majority
must still be considered as experimental. The alternative approaches to the
thyroid gland can be divided in cervical minimally invasive, extracervical
endosopic (robot-assisted) and transoral operations (natural orifice transluminal
endoscopic surgery, NOTES). Since conventional thyroid operations are
standardized procedures with low complication rates, alternative approaches to
the thyroid gland are considered critically in Germany. The request for a perfect
cosmetic result should not overweigh patients' safety. Only a few alternative
approaches (e. g. MIVAT, RAT) can yet be considered as a safe addition in
experienced hands in highly selected patients.
PMID- 28497165
TI - Linear relationship between lateralization of the bicipital groove and humeral
retroversion and its link with the biepicondylar humeral line. Anatomical study
of seventy cadaveric humerus scans.
AB - INTRODUCTION: Morphological studies of the humerus have shown that the position
of the bicipital groove varies with the individual and the retroversion of the
humeral head. Depending on the authors, these two parameters are independent or
associated. This study evaluated the relationship between the humeral head axis
and its retroversion and the bicipital groove relative to the humeral
biepicondylar line. MATERIALS AND METHODS: Seventy cadaveric humeri were scanned
to obtain 3D reconstructions. Views of the 3D reconstruction from above showed
the bicondylar line, the bicipital groove and the humeral head on a single image.
After measuring the humeral retroversion angle and the bicipital groove angle
relative to the bicondylar line, we assessed the relationship between these two
angles with Pearson's correlation coefficient. RESULTS: Pearson's correlation
coefficient indicated a significant linear correlation between the angle of the
groove and the angle of humeral retroversion based on the 70 cadaveric humeral
bones (the p-value was 7.510-7, the correlation coefficient was -0.5515, and the
95% confidence interval was (-0.6962; -0.3636)). Our study thus demonstrates that
the less lateralized the bicipital groove is, the greater the humeral
retroversion will be. CONCLUSION: We demonstrated a linear relationship between
humeral head retroversion and bicipital groove lateralization. Within our
reliability interval, this relationship can be used in clinical practice to
evaluate retroversion without resorting to CT of the entire humerus.
PMID- 28497164
TI - Metformin prevents ischaemic ventricular fibrillation in metabolically normal
pigs.
AB - AIMS/HYPOTHESIS: Metformin is the drug most often used to treat type 2 diabetes.
Evidence suggests that metformin may reduce mortality of individuals with type 2
diabetes, but the mechanism of such an effect is unknown and outcomes of
metformin treatment in people without diabetes have not been determined. If
metformin favourably affected mortality of non-diabetic individuals, it might
have even broader therapeutic utility. We evaluated the effect of metformin on
myocardial energetics and ischaemic ventricular fibrillation (VF) in
metabolically normal pigs. METHODS: Domestic farm pigs were treated with
metformin (30 mg kg-1 day-1 orally for 2-3 weeks; n = 36) or received no
treatment (n = 37). Under anaesthesia, pigs underwent up to 90 min low-flow
regional myocardial ischaemia followed by 45 min of reperfusion. Pigs were
monitored for arrhythmia, monophasic action potential morphology, haemodynamics
and myocardial substrate utilisation, AMP-activated protein kinase (AMPK)
phosphorylation activity and ATP concentration. RESULTS: Death due to VF occurred
in 12% of pigs treated with metformin compared with 50% of untreated controls (p
= 0.03). The anti-fibrillatory effect of metformin was associated with
attenuation of action potential shortening in ischaemic myocardium (p = 0.02) and
attenuation of the difference in action potential duration between ischaemic and
non-ischaemic regions (p < 0.001) compared with untreated controls. Metformin had
no effect on myocardial contractile function, oxygen consumption, or glucose or
lactate utilisation. During ischaemia, however, metformin treatment amplified the
activation of AMPK and preserved ATP concentration in myocardium compared with
untreated controls (each p < 0.05). CONCLUSIONS/INTERPRETATION: Chronic treatment
of metabolically normal pigs with metformin at a clinically relevant dose reduces
mortality from ischaemic VF. This protection is associated with preservation of
myocardial energetics during ischaemia. Maintenance of myocardial ATP
concentration during ischaemia is likely to prevent action potential shortening,
heterogeneity of repolarisation, and propensity for lethal arrhythmia. The
findings suggest that metformin might be protective in non-diabetic individuals
with coronary heart disease.
PMID- 28497166
TI - Biomechanical evaluation of straight antegrade nailing in proximal humeral
fractures: the rationale of the "proximal anchoring point".
AB - PURPOSE: Varus failure is one of the most common failure modes following surgical
treatment of proximal humeral fractures. Straight antegrade nails (SAN)
theoretically provide increased stability by anchoring to the densest zone of the
proximal humerus (subchondral zone) with the end of the nail. The aim of this
study was to biomechanically investigate the characteristics of this "proximal
anchoring point" (PAP). We hypothesized that the PAP would improve stability
compared to the same construct without the PAP. METHODS: Straight antegrade
humeral nailing was performed in 20 matched pairs of human cadaveric humeri for a
simulated unstable two-part fracture. RESULTS: Biomechanical testing, with
stepwise increasing cyclic axial loading (50-N increments each 100 cycles) at an
angle of 20 degrees abduction revealed significantly higher median loads to
failure for SAN constructs with the PAP (median, 450 N; range, 200-1.000 N)
compared to those without the PAP (median, 325 N; range, 100-500 N; p = 0.009).
SAN constructs with press-fit proximal extensions (endcaps) showed similar median
loads to failure (median, 400 N; range, 200-650 N), when compared to the
undersized, commercially available SAN endcaps (median, 450 N; range, 200-600 N;
p = 0.240). CONCLUSIONS: The PAP provided significantly increased stability in
SAN constructs compared to the same setup without this additional proximal
anchoring point. Varus-displacing forces to the humeral head were superiorly
reduced in this setting. This study provides biomechanical evidence for the
"proximal anchoring point's" rationale. Straight antegrade humeral nailing may be
beneficial for patients undergoing surgical treatment for unstable proximal
humeral fractures to decrease secondary varus displacement and thus potentially
reduce revision rates.
PMID- 28497167
TI - Results of arthroscopic Bankart repair with Hill-Sachs remplissage for anterior
shoulder instability.
AB - PURPOSE: The aim of this study was to evaluate mid-term outcomes of Bankart
repair with Hill-Sachs remplissage (BHSR) and to highlight prognostic factors of
failure. METHODS: Thirty-four patients operated on for anterior shoulder
instability with BHSR were enrolled in a prospective non-randomised study.
Clinical and radiographic evaluation was performed at 1.5, three, six months and
yearly thereafter. Outcome measures included Rowe and Walch-Duplay score.
RESULTS: At mean follow-up of 35 months (24-63), the Rowe and Walch-Duplay scores
reached respectively 92.7 and 88.2 points. The mean deficit in external rotation
was 6 degrees in ER1 and 1 degrees in ER2 (p = 0.4, p = 0.9 respectively). Five
patients (14.7%) had a recurrence of instability and three others had a
persistent anterior apprehension. In the failure group, the Hill-Sachs lesion was
deeper (26% vs 19% of the humeral diameter; p = 0.04) and range of motion at 1.5
months postoperatively was greater. Age at surgery, pre-operative instability
severity index score (ISIS), hyperlaxity, type and level of sport, amount of
glenoid bone loss had no correlation with failure rate. CONCLUSIONS: The rate of
failure at mid-term follow-up of BHSR was higher than commonly reported. The
premature recovery of range of motion seems to be a clinical sign of failure at
follow-up. Moreover, in case of deep Hill-Sachs lesion (>20%) an alternative
procedure should be considered. LEVEL OF EVIDENCE: Level IV.
PMID- 28497168
TI - Relationship between geographical origin, seed size and genetic diversity in faba
bean (Vicia faba L.) as revealed by SSR markers.
AB - Faba bean (Vicia faba L.) is an important legume species because of its high
protein and starch content. Broad bean can be grown in different climatic
conditions and is an ideal rotation crop because of the nitrogen fixing bacteria
in its roots. In this work, 255 faba bean germplasm accessions were characterized
using 32 SSR primers which yielded 302 polymorphic fragments. According to the
results, faba bean individuals were divided into two main groups based on the
neighbor-joining algorithm (r = 0.91) with some clustering based on geographical
origin as well as seed size. Population structure was also determined and agreed
with the dendrogram analysis in splitting the accessions into two subpopulations.
Analysis of molecular variance (AMOVA) revealed high levels of within population
genetic variation. Genetic similarity and geographical proximity were related
with separation of European accessions from African and Asian ones.
Interestingly, there was no significant difference between landrace (38%) and
cultivar (40%) diversity indicating that genetic variability has not yet been
lost due to breeding. A total of 44 genetically well-characterized faba bean
individuals were selected for a core collection to be further examined for yield
and nutritional traits.
PMID- 28497169
TI - Homogeneous pancreatic cancer spheroids mimic growth pattern of circulating tumor
cell clusters and macrometastases: displaying heterogeneity and crater-like
structure on inner layer.
AB - PURPOSE: Pancreatic cancer 3D in vitro models including multicellular tumor
spheroid (MCTS), single cell-derived tumor spheroid (SCTS), tissue-derived tumor
spheroid, and organotypic models provided powerful platforms to mimic in vivo
tumor. Recent work supports that circulating tumor cell (CTC) clusters are more
efficient in metastasis seeding than single CTCs. The purpose of this study is to
establish 3D culture models which can mimic single CTC, monoclonal CTC clusters,
and the expansion of macrometastases. METHODS: Seven pancreatic ductal
adenocarcinoma cell lines were used to establish MCTS and SCTS using hanging drop
and ultra-low attachment plates. Spheroid immunofluorescence staining, spheroid
formation assay, immunoblotting, and literature review were performed to
investigate molecular biomarkers and the morphological characteristics of
pancreatic tumor spheroids. RESULTS: Single cells experienced different growth
patterns to form SCTS, like signet ring-like cells, blastula-like structures, and
solid core spheroids. However, golf ball-like hollow spheroids could also be
detected, especially when DanG and Capan-1 cells were cultivated with fibroblast
conditioned medium (p < 0.05). The size of golf ball-like hollow spheroids hardly
grew after getting matured. Only DanG and Capan-1 could establish SCTS- and MCTS
derived hollow spheroids using hanging drop plates and ultra-low attachment
plates. Other PDA cell lines could also establish tumor spheroid with hanging
drop plates by adding methylated cellulose. Tumor spheroids derived from
pancreatic cancer cell line DanG possessed asymmetrically distributed
proliferation center, immune-checkpoint properties. beta-catenin, Ki-67, and F
actin were active surrounding the crater-like structure distributing on the inner
layer of viable rim cover of the spheroids, which was relevant to well
differentiated tumor cells. CONCLUSIONS: It is possible to establish 3D CTC
cluster models from homogenous PDA cell lines using hanging drop and ultra-low
attachment plates. PDA cell line displays its own intrinsic properties or
heterogeneity. The mechanism of formation of the crater-like structure as well as
golf ball-like structure needs further exploration.
PMID- 28497170
TI - High systemic and testicular thermolytic efficiency during heat tolerance test
reflects better semen quality in rams of tropical breeds.
AB - This study aimed to assess the capacity of Morada Nova (MN) and Santa Ines (SIN)
rams to maintain body and testicular homeothermy under thermal challenge. For 5
days in the summer, 16 males (SIN = 7 and MN = 9) underwent a heat tolerance
test, i.e., period 1-animals maintained in the shade (11 to 12 h); period 2
animals exposed to sunlight (12 to 13 h); and period 3-animals returned to the
shade (13 to 14 h). The respiratory rate, heart rate, rectal temperature, and
infrared surface temperatures (IRT) of the trunk, back, eyeball, and testicles
were assessed in each period. The index of capacity of tolerance to insolation
(ICTI), which indicates the animals' level of adaptability, was calculated for
each animal. Semen quality and testicular parenchyma integrity were assessed
before and after the thermal challenge. Statistical analyses were performed at 5%
significance. In period 1, the variables had baseline values for both genotypes.
In period 2, the variables involved in thermolysis significantly increased (P <
0.05), which matches a thermal discomfort situation. In period 3, the variables
returned to baseline values and some values were lower than those in period 1.
Semen quality and testicular parenchyma integrity suffered no negative effects
with the thermal challenge. IRT ocular and IRT testicular were positively
correlated (P < 0.05). It is concluded that MN and SIN rams had efficient
thermolytic mechanisms that favor preserving gonadal functionality. The animals
were considered resilient to a thermal challenge. In addition, infrared
thermography was an efficient tool to verify body and testicular
thermoregulation.
PMID- 28497171
TI - Measuring facial cooling in outdoor windy winter conditions: an exploratory
study.
AB - Winter clothing provides insulation for almost all of a person's body, but in
most situations, a person's face remains uncovered even in cold windy weather.
This exploratory study used thermal imagery to record the rate of cooling of the
faces of volunteers in a range of winter air temperatures and wind speeds.
Different areas of the faces cooled at different rates with the areas around the
eyes and neck cooling at the slowest rate, and the nose and cheeks cooling at the
fastest rate. In all cases, the faces cooled at an approximately logarithmic
decay for the first few minutes. This was followed by a small rise in the
temperature of the face for a few minutes, which was then followed by an
uninterrupted logarithmic decay. Volunteers were told to indicate when their face
was so cold that they wanted to end the test. The total amount of time and the
facial temperature at the end of each trial were recorded. The results provide
insight into the way faces cool in uncontrolled, outdoor winter conditions.
PMID- 28497173
TI - Identifying Effective and Sustainable Measures for Community-Based Environmental
Monitoring.
AB - Resource development projects typically result in monitoring programs that fail
to fully consider the values and participation of surrounding communities. Also,
monitoring protocols for single environmental values can be insufficient for
addressing the cumulative impacts of resource development. Community-based
environmental monitoring (CBEM) has emerged as a way to meaningfully include
local citizens in the decision-making process and assessment of the development
of natural resources. Our research explored how to develop effective and
sustainable CBEM. Interviews were conducted with staff from 15 CBEM programs
established across Canada to identify criteria of what constitutes effective
CBEM. Results demonstrate that CBEM offers an effective, locally adapted, and
culturally applicable approach to facilitate community participation in natural
resource management and to track environmental change. Benefits of CBEM include:
locally relevant monitoring protocols, inclusion of cumulative impacts, better
informed decision-making, and increased awareness and collaboration amongst
community, governments, and proponents. Challenges associated with CBEM are cost,
capacity, longevity, distribution of results, and establishing credibility. This
research validates the use of CBEM for improving resource management.
PMID- 28497174
TI - Stability assessment of a new antithrombotic small peptide, Arg-Gly-Asp-Trp-Arg
(RGDWR), and its derivative.
AB - OBJECTIVE: To assess the stabilities of Arg-Gly-Asp-Trp-Arg (RGDWR, designated as
RWR), a new patented antithrombotic small peptide, and its derivative with omega
aminocaprylic acid on its N-terminus (omegaRWR). RESULTS: RWR in rat plasma was
decreased by between 32 and 48% after 4 h incubation on ice, indicating its
instability in plasma. In contrast, omegaRWR in plasma remained at 96-107%.
Concentration changes were within 6.2% for omegaRWR after storage in various
conditions. omegaRWR is therefore stable in rat plasma, as well as under
different storage methods. Furthermore, omega-aminocaprylic acid added onto the
RWR peptide did not affect its antiplatelet aggregation activity. CONCLUSIONS: A
novel small peptide, omegaRWR, has been developed with a good stability for
possible antithrombotic use.
PMID- 28497175
TI - Characterization and role of a 2',3'-cyclic phosphodiesterase from Deinococcus
radiodurans.
AB - OBJECTIVES: A 2',3'-cyclic phosphodiesterase gene (drCPDase) has been
characterized from Deinococcus radiodurans and is involved in the robust
resistance of this organism. RESULTS: Cells lacking 2',3'-cyclic
phosphodiesterase gene (drCPDase) showed modest growth defects and displayed
increased sensitivities to high doses of various DNA-damaging agents including
ionizing radiation, mitomycin C, UV and H2O2. The transcriptional level of
drCPDase increased after H2O2 treatment. Additional nucleotide monophosphate
partially recovered the phenotype of drCPDase knockout cells. Complementation of
E. coli with drCPDase resulted in enhanced H2O2 resistance. CONCLUSIONS: The
2',3'-cyclic phosphodiesterase (drCPDase) contributes to the extreme resistance
of D. radiodurans and is presumably involved in damaged nucleotide
detoxification.
PMID- 28497177
TI - Critical appraisal of health-state utility values used in breast cancer-related
cost-utility analyses.
AB - PURPOSE: To review the data sources of health-state utility values (HSUVs), as
well as their elicitation and use, in 140 breast cancer-related cost-utility
analyses (CUAs), and to provide a critical appraisal of these. METHODS: A
checklist was developed to guide the process of the critical appraisal. It is
divided into three parts: the data source (three questions), elicitation method
(four questions), and use (ten questions) of HSUVs in CUAs. Two independent
reviewers performed the data extraction. A consensus was reached in case of
disagreements. Data sources were categorized as "original study," "derived from
the literature," or "other." RESULTS: The data source of HSUVs was always
specified. When HSUVs were derived from the literature (90% of cases), the
authors referred to a median number of two references as data sources. The
critical appraisal of the elicitation of HSUVs in CUAs revealed considerable
variability in terms of the quality of the reporting of the data source selection
of HSUV. More details were provided by authors when HSUVs were elicited from an
original study rather than derived from the literature. The use of HSUVs elicited
from an original study was generally better described in terms of the checklist
than were those derived from the literature. CONCLUSIONS: Based on the developed
checklist, we were able to highlight the challenges that authors are facing when
trying to adequately report HSUV used in CUAs. Our proposed checklist offers a
good starting point for encouraging more explicit and comprehensive reporting of
HSUVs in CUAs.
PMID- 28497172
TI - Deep intronic mutations and human disease.
AB - Next-generation sequencing has revolutionized clinical diagnostic testing. Yet,
for a substantial proportion of patients, sequence information restricted to
exons and exon-intron boundaries fails to identify the genetic cause of the
disease. Here we review evidence from mRNA analysis and entire genomic sequencing
indicating that pathogenic mutations can occur deep within the introns of over 75
disease-associated genes. Deleterious DNA variants located more than 100 base
pairs away from exon-intron junctions most commonly lead to pseudo-exon inclusion
due to activation of non-canonical splice sites or changes in splicing regulatory
elements. Additionally, deep intronic mutations can disrupt transcription
regulatory motifs and non-coding RNA genes. This review aims to highlight the
importance of studying variation in deep intronic sequence as a cause of
monogenic disorders as well as hereditary cancer syndromes.
PMID- 28497176
TI - Five-weekly S-1 plus cisplatin therapy combined with trastuzumab therapy in HER2
positive gastric cancer: a phase II trial and biomarker study (WJOG7212G).
AB - BACKGROUND: Five-weekly S-1 plus cisplatin (SP) therapy is the standard care for
advanced gastric or esophagogastric junction cancer (GC/EGJC) in East Asia.
However, its efficacy and safety when combined with trastuzumab therapy for human
epidermal growth factor receptor 2 (HER2)-positive advanced GC/EGJC remains
unclear. METHODS: Patients received 5-weekly SP therapy (S-1 at 40-60 mg twice
daily for 21 days plus cisplatin at 60 mg/m2 on day 8, every 5 weeks) plus
trastuzumab therapy (first dose of 8 mg/kg, then 6 mg/kg every 3 weeks). The
primary end point was the response rate, and the secondary end points included
progression-free survival, overall survival, safety, and serum biomarker levels.
RESULTS: Forty-four patients were enrolled. The response rate, progression-free
survival, and overall survival were 61% (95% confidence interval 46-76%), 5.9
months, and 16.5 months respectively. The commonest grade 3 or grade 4 adverse
events were neutropenia (30%) and anorexia (25%). A significantly higher response
rate (92% vs 43%; P = 0.008) and longer progression-free survival (median 14.5
months vs 4.2 months; P = 0.028) were observed in patients with high (n = 14)
compared with low (n = 17) pretreatment serum neuregulin 1 levels. CONCLUSIONS:
Five-weekly SP therapy combined with trastuzumab therapy showed a good antitumor
response and acceptable toxicity in HER2-positive advanced GC/EGJC. Serum
neuregulin 1 might be associated with the efficacy of this treatment regimen.
PMID- 28497178
TI - Optimization of production of C-phycocyanin and extracellular polymeric
substances by Arthrospira sp.
AB - The key factors influencing the production of C-phycocyanin (C-PC) and
extracellular polymeric substances (EPS) by photoautotrophic culture of
Arthrospira sp. were optimized using Taguchi method. Six factors were varied at
either three or two levels as follows: light intensity at three levels; three
initial culture pHs; two species of Arthrospira; three concentrations of
Zarrouk's medium; three rates of aeration of the culture with air mixed with 2%
v/v carbon dioxide; and two incubation temperatures. All cultures ran for 14
days. The optimal conditions for the production of C-PC and EPS were different.
For both products, the best cyanobacterium proved to be Arthrospira maxima
IFRPD1183. The production of C-PC was maximized with the following conditions: a
light intensity of 68 umol photons m-2 s-1 (a diurnal cycle of 16-h photoperiod
and 8-h dark period), an initial pH of 10, the full strength (100%) Zarrouk's
culture medium, an aeration rate of 0.6 vvm (air mixed with 2% v/v CO2) and a
culture temperature of 30 degrees C. The concentration of Zarrouk's medium was
the most important factor influencing the final concentration of C-PC. The
optimal conditions for maximal production of EPS were as follows: a light
intensity of 203 umol photons m-2 s-1 with the earlier specified light-dark
cycle; an initial pH of 9.5; a 50% strength of Zarrouk's medium; an aeration rate
of 0.2 vvm (air mixed with 2% v/v CO2); and a temperature of 35 degrees C.
Production of C-PC and EPS in raceway ponds is discussed.
PMID- 28497180
TI - Performance of a capnodynamic method estimating effective pulmonary blood flow
during transient and sustained hypercapnia.
AB - The capnodynamic method is a minimally invasive method continuously calculating
effective pulmonary blood flow (COEPBF), equivalent to cardiac output when intra
pulmonary shunt flow is low. The capnodynamic equation joined with a ventilator
pattern containing cyclic reoccurring expiratory holds, provides breath to breath
hemodynamic monitoring in the anesthetized patient. Its performance however,
might be affected by changes in the mixed venous content of carbon dioxide
(CvCO2). The aim of the current study was to evaluate COEPBF during rapid
measurable changes in mixed venous carbon dioxide partial pressure (PvCO2)
following ischemia-reperfusion and during sustained hypercapnia in a porcine
model. Sixteen pigs were submitted to either ischemia-reperfusion (n = 8) after
the release of an aortic balloon inflated during 30 min or to prolonged
hypercapnia (n = 8) induced by adding an instrumental dead space. Reference
cardiac output (CO) was measured by an ultrasonic flow probe placed around the
pulmonary artery trunk (COTS). Hemodynamic measurements were obtained at
baseline, end of ischemia and during the first 5 min of reperfusion as well as
during prolonged hypercapnia at high and low CO states. Ischemia-reperfusion
resulted in large changes in PvCO2, hemodynamics and lactate. Bias (limits of
agreement) was 0.7 (-0.4 to 1.8) L/min with a mean error of 28% at baseline.
COEPBF was impaired during reperfusion but agreement was restored within 5 min.
During prolonged hypercapnia, agreement remained good during changes in CO. The
mean polar angle was -4.19 degrees (-8.8 degrees to 0.42 degrees ).
Capnodynamic COEPBF is affected but recovers rapidly after transient large
changes in PvCO2 and preserves good agreement and trending ability during states
of prolonged hypercapnia at different levels of CO.
PMID- 28497179
TI - Detectable Neuropsychological Differences in Early Preclinical Alzheimer's
Disease: A Meta-Analysis.
AB - The development of methods for in vivo detection of cerebral beta amyloid
retention and tau accumulation have been increasingly useful in characterizing
preclinical Alzheimer's disease (AD). While the association between these
biomarkers and eventual AD has been demonstrated among cognitively intact older
adults, the link between biomarkers and neurocognitive ability remains unclear.
We conducted a meta-analysis to test the hypothesis that cognitively intact older
adults would show statistically discernable differences in neuropsychological
performance by amyloid status (amyloid negative = A-, amyloid positive = A+). We
secondarily hypothesized a third group characterized by either CSF tau pathology
or neurodegeneration, in addition to amyloidosis (A+/N+ or Stage 2), would show
lower neuropsychology scores than the amyloid positive group (A+/N- or Stage 1)
when compared to the amyloid negative group. Pubmed, PsychINFO, and other sources
were searched for relevant articles, yielding 775 total sources. After review for
inclusion/exclusion criteria, duplicates, and risk of bias, 61 studies were
utilized in the final meta-analysis. Results showed A+ was associated with poorer
performance in the domains of global cognitive function, memory, language,
visuospatial ability, processing speed, and attention/working memory/executive
functions when compared to A-. A+/N+ showed lower performances on memory measures
when compared to A+/N- in secondary analyses based on a smaller subset of
studies. Results support the notion that neuropsychological measures are
sensitive to different stages of preclinical AD among cognitively intact older
adults. Further research is needed to determine what constitutes meaningful
differences in neuropsychological performance among cognitively intact older
adults.
PMID- 28497182
TI - The polo-like kinase 4 gene (PLK4) is overexpressed in pediatric medulloblastoma.
PMID- 28497181
TI - New directions in fetal surgery for myelomeningocele.
AB - The treatment of children with myelomeningocele (MMC) has improved over time,
from supportive management to early postnatal closure to prenatal repair of the
defect. The Management of Myelomeningocele Study (MOMS) showed that prenatal
repair of MMC resulted in improved neurological outcomes compared to postnatal
closure. Follow-up studies showed that prenatal repair was, as with any other
fetal intervention, associated with higher rates of obstetrical complications.
There was no significant difference in urological outcomes. Long-term follow-up
of ambulatory status, executive functioning, and urological outcomes is needed to
determine the durable effects of fetal MMC repair on mobility, functional
independence, and the prevalence of renal insufficiency in patients with MMC who
survive to adulthood. The future of fetal MMC repair consists of developing
strategies to reduce maternal morbidity and improve infant outcomes. Fetoscopic
MMC repair has been suggested as an alternative to open repair that may reduce
obstetrical complications and the need for cesarean delivery in subsequent
pregnancies. Translational research using mesenchymal stromal cells to augment
fetal repair of ovine MMC has shown improvement in motor function.
PMID- 28497183
TI - Rapid contralateral progression of focal cerebral arteriopathy distinguished from
RNF213-related moyamoya disease and fibromuscular dysplasia.
AB - BACKGROUND: Focal cerebral arteriopathy includes unifocal or multifocal lesions
that are unilateral or bilateral. Large- and/or medium-sized vessels are involved
and can be visualized on angiography. CASE REPORT: We report a case of cerebral
infarction in a 9-year-old Japanese female who presented with a transient
ischemic attack. Steno-occlusion involving the distal part of the internal
carotid artery, proximal middle cerebral artery, and anterior cerebral artery was
observed. Digital subtraction angiography demonstrated a beaded appearance in the
cervical portion of the diseased internal carotid artery. Revascularization
surgery was performed 45 days after the onset. A new infarction appeared on the
other side of the anterior cerebral artery territory 7 months after the first
onset. Antiplatelets and vasodilators were administered, and no progression was
observed during 18 months of follow-up. Genetic analysis did not show ring finger
protein 213 (RNF213)-related moyamoya disease, and pathological examination
revealed no characteristics of fibromuscular dysplasia. CONCLUSION: The
radiological and genetic features coincided with focal cerebral arteriopathy,
which is a distinct entity from fibromuscular dysplasia and RNF213-related
moyamoya disease.
PMID- 28497185
TI - Reply to the Letter: "N-Butyl Cyanoacrylate Glue: The Best Hemostatic Embolic
Agent for Patients with Acute Arterial Bleeding".
PMID- 28497184
TI - Management of hydrocephalus in pediatric metastatic tumors of the posterior fossa
at presentation.
AB - PURPOSE: Presence of metastases in newly diagnosed pediatric posterior fossa
tumors (PFT) is not a rare situation, but optimal treatment of associated
hydrocephalus in these children has remained undetermined. METHODS: Twenty-nine
children treated between January 2005 and December 2015 for a metastatic PFT
associated with hydrocephalus constituted the study cohort. Patients were divided
into three groups: ventriculoperitoneal shunt (VPS), endoscopic third
ventriculostomy (ETV), and temporary ventricular drainage before or during tumor
resection (PVD). RESULTS: There were 4 VPS, 18 ETV, and 7 PVD. The global
incidence of CSF diversion failure was 52%. No case of dysfunction or
dissemination of metastatic cells occurred in the VPS group. Recurrence of
hydrocephalus occurred in 55% of the ETV group. Presence of multiple macroscopic
metastases and CSF metastatic cells after tumor surgery was associated with ETV
failure. Fifty-seven percent of the children in the PVD group were reoperated
after an average time of 53 days. Specific oncologic treatment was initiated
earlier in the VPS group (11 days) compared to ETV (27 days) and PVD (23 days)
groups. CONCLUSIONS: ETV should be avoided in cases of multiple macroscopic
metastases, and children who underwent ETV must be followed carefully when
metastatic cells are present in CSF after tumor surgery. External ventricular
drainage before or during surgical removal should not be considered as a final
option to treat hydrocephalus. VPS remains a safe alternative in this situation
and allows an early specific oncologic treatment.
PMID- 28497186
TI - Microwave Ablation of the Lung in a Porcine Model: Vessel Diameter Predicts
Pulmonary Artery Occlusion.
AB - PURPOSE: To determine the size of pulmonary artery (PA) at risk for occlusion
during percutaneous microwave ablation and to assess the effect of vessel
diameter, number, and patency, on ablation zone volume. MATERIALS AND METHODS:
Computed tomography (CT) fluoroscopy-guided percutaneous microwave ablations were
performed in 8 pigs under general anesthesia. All ablations were performed at 65
W for 5 min with a single 17-gauge antenna positioned in the central third of the
lungs. A CT pulmonary angiogram was performed immediately after the ablations.
The maximum diameter, number and patency of PA branches within each ablation zone
were recorded. Ablation volumes were measured at gross dissection and with CT.
Student's t test was used to compare ablation zone volumes among groups. RESULTS:
Twenty-one pulmonary ablations were performed. Six of the ablation zones (29%)
contained at least 1 occluded PA branch. The mean diameter of the occluded PA
branches in the ablation zones (2.4 mm; range, 2.0-2.8 mm) was significantly
smaller than non-occluded PA branches (3.7 mm; range: 2.1-6.9 mm; p = 0.009). No
PA branches >=3 mm in size were occluded. There was no significant difference in
volume of gross ablation zones that contained occluded versus non-occluded PAs (p
= 0.42), one versus multiple PAs (p = 0.71), or PAs <3 mm versus >=3 mm in
diameter (p = 0.44). CONCLUSIONS: PAs >=3 mm in size have a low risk for
iatrogenic occlusion during percutaneous microwave ablation. The presence of
multiple adjacent PA branches, an occluded PA branch, and a vessel diameter >=3
mm within the ablation zone had no observed effect on ablation zone volume.
PMID- 28497187
TI - Radiation-Induced Skin Injuries to Patients: What the Interventional Radiologist
Needs to Know.
AB - For a long time, radiation-induced skin injuries were only encountered in
patients undergoing radiation therapy. In diagnostic radiology, radiation
exposures of patients causing skin injuries were extremely rare. The introduction
of fast multislice CT scanners and fluoroscopically guided interventions (FGI)
changed the situation. Both methods carry the risk of excessive high doses to the
skin of patients resulting in skin injuries. In the early nineties, several
reports of epilation and skin injuries following CT brain perfusion studies were
published. During the same time, several papers reported skin injuries following
FGI, especially after percutaneous coronary interventions and neuroembolisations.
Thus, CT and FGI are of major concern regarding radiation safety since both
methods can apply doses to patients exceeding 5 Gy (National Council on Radiation
Protection and Measurements threshold for substantial radiation dose level). This
paper reviews the problem of skin injuries observed after FGI. Also, some
practical advices are given how to effectively avoid skin injuries. In addition,
guidelines are discussed how to deal with patients who were exposed to a
potentially dangerous radiation skin dose during medically justified
interventional procedures.
PMID- 28497188
TI - Pediatric Percutaneous Osteoid Osteoma Ablation: Cone-Beam CT with Fluoroscopic
Overlay Versus Conventional CT Guidance.
AB - PURPOSE: To compare technical success, clinical success, complications, radiation
dose, and total room utilization time for osteoid osteoma thermal (radiofrequency
or microwave) ablation using cone-beam computed tomography (CBCT) with two-axis
fluoroscopic navigational overlay versus conventional computed tomography (CT)
guidance. MATERIALS AND METHODS: A retrospective review was performed to identify
all osteoid osteoma ablations performed over a 5.5-year period at a single
tertiary care pediatric hospital. Twenty-five ablations (15 radiofrequency and 10
microwave) in 23 patients undergoing fluoroscopic CBCT-guided osteoid osteoma
ablation were compared to 35 ablations (35 radiofrequency) in 32 patients
undergoing ablation via conventional CT guidance. Dose area product and dose
length product were recorded for CBCT and conventional CT, respectively, and
converted to effective doses. Technical success, clinical success (cessation of
pain and medication use 1 month after ablation), complications, radiation dose,
and total room utilization time were compared. RESULTS: All procedures were
technically successful. Twenty-two of 25 (88.0%) CBCT and 31 of 35 (88.6%)
conventional CT-guided ablations achieved immediate clinical success. There were
two minor complications in each group and no major complications. Mean effective
radiation dose was significantly lower for CBCT compared to CT guidance (0.12 vs.
0.39 mSv, p = 0.02). Mean total room utilization time for CBCT was longer (133.5
vs. 97.5 min, p = 0.0001). CONCLUSIONS: Fluoroscopic CBCT guidance for
percutaneous osteoid osteoma ablation yields similar technical and clinical
success, reduced radiation dose, and increased total room utilization time
compared to conventional CT guidance.
PMID- 28497189
TI - Quantification of mitral regurgitation during percutaneous mitral valve repair:
added value of simultaneous hemodynamic and 3D echocardiographic assessment.
AB - The objective of this study was to investigate the usefulness of intraprocedural
hemodynamic monitoring for MR evaluation during pMRV. Assessment of mitral
regurgitation (MR) during percutaneous mitral valve repair (pMVR) procedure is
challenging. 3D color Doppler allows exact quantification of MR, but is
technically demanding. Sixty patients with moderate to severe MR (14 with
structural and 46 functional MR) were included in the study. Intraprocedural
pressure curves were continuously obtained in the left atrium (LA) and left
ventricle (LV). Transesophageal echocardiography was performed using 3D color
Doppler derived mean vena contracta area (VCAmean) and mitral regurgitation
volume (RegVol) to quantify MR severity before and after each clip implantation.
In the entire patient group, strongest correlations were observed firstly between
VCA and the raise of the ascending limb of the left atrial V pressure wave
(Vascend; r = 0.58, p < 0.001) and secondly between the difference of peak V wave
pressure and mean LA pressure divided by systolic LV pressure [(Vpeak - LAmean) -
LVsystole; r = 0.53, p < 0.001]. In patients with structural MR, the highest area
under the ROC curve for prediction of mild MR (VCAmean < 0.2 cm2 and RegVol < 30
ml) after clip implantation was found for Vascend (AUC 0.89, p < 0.001) whereas
in functional MR calculation of (Vpeak - LAmean) - LVsystole showed the highest
predictive value (AUC 0.69, p = 0.003). Invasive pressure monitoring can give a
direct feedback with regard to the success of clip placement during pMVR.
PMID- 28497190
TI - Abstracts of the ECTS congress 2017.
PMID- 28497191
TI - Evaluation of the coronary circulation and calcification in children on regular
hemodialysis.
AB - BACKGROUND: The objective of this study was to evaluate the coronary circulation
and calcification in children with end-stage renal disease (ESRD) on
hemodialysis. METHODS: A total of 50 children with ESRD and 50 healthy controls
were enrolled in the study. Cardiac functions and coronary blood flow were
evaluated with conventional and tissue Doppler echocardiography. Coronary artery
calcification (CAC) was evaluated using high-resolution multidetector computed
tomography (CT). RESULTS: The hyperemic coronary flow volume (CFV) and coronary
flow reserve were significantly lower in the patient group than in the controls,
while there was no significant difference in the baseline CFV between the two
groups. Hypertension was present in 60% and CAC was observed in 20% of the
children in the patient group. CAC was present in 30% of the children in the
hypertensive subgroup. The left ventricle myocardial performance index (LV MPI),
CAC score, duration of hypertension and level of diastolic blood pressure were
independent predictors of the coronary blood flow, and LV MPI, serum parathyroid
hormone, duration of dialysis and E'/A' mitral valve were independent predictors
of coronary calcification. CONCLUSION: High diastolic blood pressure, long
duration of hypertension, high LV MPI and increased CAC scores are independent
risk factors for impaired coronary blood flow in children with ESRD.
PMID- 28497192
TI - Redox changes of ferredoxin, P700, and plastocyanin measured simultaneously in
intact leaves.
AB - Properties and performance of the recently introduced Dual/KLAS-NIR
spectrophotometer for simultaneous measurements of ferredoxin (Fd), P700, and
plastocyanin (PC) redox changes, together with whole leaf chlorophyll a (Chl)
fluorescence (emission >760, 540 nm excitation) are outlined. Spectral
information on in vivo Fd, P700, and PC in the near-infrared region (NIR, 780
1000 nm) is presented, on which the new approach is based. Examples of
application focus on dark-light and light-dark transitions, where maximal redox
changes of Fd occur. After dark-adaptation, Fd reduction induced by moderate
light parallels the Kautsky effect of Chl fluorescence induction. Both signals
are affected analogously by removal of O2. A rapid type of Fd reoxidation,
observed after a short pulse of light before light activation of linear electron
transport (LET), is more pronounced in C4 compared to C3 leaves and interpreted
to reflect cyclic PS I (CET). Light activation of LET, as assessed via the rate
of Fd reoxidation after short light pulses, occurs at very low intensities and is
slowly reversed (half-time ca. 20 min). Illumination with strong far-red light
(FR, 740 nm) reveals two fractions of PS I, PS I (LET), and PS I (CET), differing
in the rates of Fd reoxidation upon FR-off and the apparent equilibrium constants
between P700 and PC. Parallel information on oxidation of Fd and reduction of
P700 plus PC proves essential for identification of CET. Comparison of maize (C4)
with sunflower and ivy (C3) responses leads to the conclusion that segregation of
two types of PS I may not only exist in C4 (mesophyll and bundle sheath cells),
but also in C3 photosynthesis (grana margins plus end membranes and stroma
lamellae).
PMID- 28497193
TI - Evaluation of new Cu(II) complexes as a novel class of inhibitors against plant
carbonic anhydrase, glutathione reductase, and photosynthetic activity in
photosystem II.
AB - Increasing inefficiency of production of important agricultural plants raises one
of the biggest problems in the modern world. Herbicide application is still the
best method of weed management. Traditional herbicides blocking only one of the
plant metabolic pathways is ineffective due to the rapid growth of herbicide
resistant weeds. The synthesis of novel compounds effectively suppressing several
metabolic processes, and therefore achieving the synergism effect would serve as
the alternative approach to weed problem. For this reason, recently, we
synthesized a series of nine novel Cu(II) complexes and four ligands,
characterized them with different analyses techniques, and carried out their
primary evaluation as inhibitors of photosynthetic electron transfer in spinach
thylakoids (design, synthesis, and evaluation of a series of Cu(II) based metal
organic complexes as possible inhibitors of photosynthesis, J Photochem Photobiol
B, submitted). Here, we evaluated in vitro inhibitory potency of these agents
against: photochemistry and carbonic anhydrase activity of photosystem II (PSII);
alpha-carbonic anhydrase from bovine erythrocytes; as well as glutathione
reductase from chloroplast and baker's yeast. Our results show that all Cu(II)
complexes excellently inhibit glutathione reductase and PSII carbonic anhydrase
activity. Some of them also decently inhibit PSII photosynthetic activity.
PMID- 28497194
TI - Treatment and outcomes of recurrent hepatocellular carcinomas.
AB - PURPOSE: Surgery is one of the best options for curative treatment of
hepatocellular carcinomas (HCC). Recurrences are nevertheless common (45-75%).
This study aimed to compare overall survival (OS) of patients with recurrent HCC
after primary resection to OS of patients without recurrence. METHODS: A
retrospective review of all HCC patients operated between 1993 and 2015 was
performed. Median and 5-year OS were calculated. RESULTS: This study included 147
HCC patients. Sixty-seven patients presented a recurrence (46%). Patients with
recurrence had a worse prognosis than those without recurrence (median OS 63 vs.
82 months, 5-year OS 47 vs. 54%, p = 0.036). First-line performed treatments were
radiofrequency ablation (18, RFA), chemo-embolization (16, TACE), repeat
hepatectomy (10), systemic chemotherapy (4), radio-embolization (1), and
alcoholization (1). Palliative care was performed in 17 patients. Median OS of
patients treated by RFA, TACE, or repeat hepatectomy were similar (77, 71, and 84
months, p = 0.735). Patients treated with chemotherapy/palliative care had lower
median OS compared to interventional treatments (20 vs. 77 months, p < 0.0001).
CONCLUSIONS: Recurrence after surgical HCC resection is frequent and negatively
impacts OS. Interventional treatments of recurrences offered improved outcomes
compared to medical care. In selected patients, RFA, TACE, and repeat hepatectomy
allowed similar OS as non-recurrent cases.
PMID- 28497195
TI - Olfaction in a viscous environment: the "color" of sexual smells in Temora
longicornis.
AB - We investigate chemical aspects of mating in the marine copepod Temora
longicornis (Copepoda, Calanoidea). Our emphasis is the female pheromone
signaling in form of well-defined trails for males to follow, observed in Doall
et al. (Phil Trans R Soc Lond B 353:681-689, 1998). The viscous environment and
the properties of the odorants play important roles as the spread of the
pheromone trail limits the time during which it is useful for tracing. A key
observation from our earlier work is the ability of a searching male to detect
the direction of the female and to correct its swimming direction if necessary.
We propose a simple mathematical model for the spread of a pheromone from a
moving source and carry out numerical simulations of two possible detection
mechanisms. We find that a searching agent that is capable to detect a ratio
outperforms a searcher that depends on the gradient of a single compound. This
suggests that copepod sex pheromones consist of blends of chemical compounds, and
that a ratio detection mechanism similar to that in airborne insects is at work.
PMID- 28497196
TI - An objective view of biological diversity: how history and epistemology shaped
current treatment.
AB - The concept of biological diversity has inspired important discussions throughout
the history of ecology. Although its meaning and usefulness have been questioned,
it is currently one of the key artifacts of ecology. One way to try to understand
why such a concept has undergone so many discussions is to examine its emergence
and history from the epistemology perspective. In the present work, we
investigated how the emergence of mechanical objectivity (as an epistemic virtue)
and trained judgment affected how ecologists address the concept of biological
diversity. Thus, we employed the theoretical framework of objectivity (provided
by Daston and Galison in Objectivity. Zone Books, New York, 2007) to analyze
different periods of scientific literature in ecology ("initial period": end of
the nineteenth century and beginning of the twentieth century; "intermediate
period": mid-twentieth century; "contemporary period": from the second half of
the 1980s). Our results showed that the emergence of mechanical objectivity and
trained judgment affected biological diversity research. In particular, the ideal
of objectivity behind the way in which the concept of biological diversity is
addressed in different fields of contemporary ecology could not be the same.
PMID- 28497197
TI - Erratum to: Management of Recurrent Retroperitoneal Sarcoma (RPS) in the Adult: A
Consensus Approach from the Trans-Atlantic RPS Working Group.
PMID- 28497198
TI - Diagnostic performance of 68Ga-PSMA-11 (HBED-CC) PET/CT in patients with
recurrent prostate cancer: evaluation in 1007 patients.
AB - PURPOSE: Since the clinical introduction of 68Ga-PSMA-11 PET/CT, this imaging
method has rapidly spread and is now regarded as a significant step forward in
the diagnosis of recurrent prostate cancer (PCa). The aim of this study was to
analyse the influence of several variables with possible influence on PSMA ligand
uptake in a large cohort. METHODS: We performed a retrospective analysis of 1007
consecutive patients who were scanned with 68Ga-PSMA-11 PET/CT (1 h after
injection) from January 2014 to January 2017 to detect recurrent disease.
Patients with untreated primary PCa or patients referred for PSMA radioligand
therapy were excluded. The possible effects of different variables including PSA
level and PSA doubling time (PSADT), PSA velocity (PSAVel), Gleason score (GSC,
including separate analysis of GSC 7a and 7b), ongoing androgen deprivation
therapy (ADT), patient age and amount of injected activity were evaluated.
RESULTS: In 79.5% of patients at least one lesion with characteristics suggestive
of recurrent PCa was detected. A pathological (positive) PET/CT scan was
associated with PSA level and ADT. GSC, amount of injected activity, patient age,
PSADT and PSAVel were not associated with a positive PET/CT scan in multivariate
analysis. CONCLUSION: 68Ga-PSMA-11 PET/CT detects tumour lesions in a high
percentage of patients with recurrent PCa. Tumour detection is clearly associated
with PSA level and ADT. Only a tendency for an association without statistical
significance was found between higher GSC and a higher probability of a
pathological PET/CT scan. No associations were found between a pathological 68Ga
PSMA-11 PET/CT scan and patient age, amount of injected activity, PSADT or
PSAVel.
PMID- 28497199
TI - Arachidonic Acid Induces ARE/Nrf2-Dependent Heme Oxygenase-1 Transcription in Rat
Brain Astrocytes.
AB - Arachidonic acid (AA) is a major product of phospholipid hydrolysis catalyzed by
phospholipase A2 during neurodegenerative diseases. AA exerts as a second
messenger to regulate various signaling components which may be involved in
different pathophysiological processes. Astrocytes are the main types of CNS
resident cells which maintain and support the physiological function of brain. AA
has been shown to induce ROS generation through activation of NADPH oxidases
(Noxs) which may play a key role in the expression of heme oxygenase-1 (HO-1).
Therefore, this study was designed to investigate the mechanisms underlying AA
induced HO-1 expression in rat brain astrocytes (RBA-1). We found that AA induced
HO-1 protein and mRNA expression and promoter activity in RBA-1, which was
mediated through the synthesis of 15-deoxy-Delta12,14-prostaglandin D2-activated
peroxisome proliferator-activated receptor-gamma (PPARgamma) receptors. This note
was confirmed by transfection with PPARgamma small interfering RNAs (siRNA) which
attenuated the AA-mediated responses. AA-induced HO-1 expression was mediated
through Nox/ROS generation, which was inhibited by Nox inhibitors
(diphenyleneiodonium and apocynin) and ROS scavengers (N-acetyl cysteine).
Moreover, AA-induced HO-1 expression was mediated through phosphorylation of Src,
Pyk2, platelet-derived growth factor, PI3K/Akt, and ERK1/2 which were inhibited
by the pharmacological inhibitors including PP1, PF431396, AG1296, LY294002, and
U0126 or by transfection with respective siRNAs. AA-enhanced Nrf2 expression and
HO-1 promoter activity was inhibited by transfection with Nrf2 siRNA or by these
pharmacological inhibitors. Furthermore, chromatin immunoprecipitation assay
confirmed that Nrf2 and PPARgamma were associated with the proximal antioxidant
response element (ARE)-binding site on HO-1 promoter, suggesting that
Nrf2/PPARgamma are key transcription factors modulating HO-1 expression. AA
induced ARE promoter activity was also reduced by these pharmacological
inhibitors. These findings suggested that AA increases formation of Nrf2 and
PPARgamma complex and binding with ARE1 binding site through Src, Pyk2, PI3K/Akt,
and ERK1/2, which further induced HO-1 expression in RBA-1 cells.
PMID- 28497200
TI - Effect of Lipoic Acid on the Biochemical Mechanisms of Resistance to Bortezomib
in SH-SY5Y Neuroblastoma Cells.
AB - Neuroblastoma (NB) is an extracranial solid cancer and the most common cancer in
infancy. Despite the standard treatment for NB is based on the combination of
chemotherapeutic drugs such as doxorubicin, vincristine, cyclophosphamide, and
cisplatin, chemoresistance occurs over the time. The aim of the present research
was to evaluate the effect of bortezomib (BTZ) (50 nM) on NB cell viability and
how lipoic acid (ALA) (100 MUM) modifies pharmacological response to this
chemotherapeutic agent. Cell viability was assessed by ATP luminescence assay
whereas expression of oxidative stress marker (i.e., heme oxygenase-1) and
endoplasmic reticulum stress proteins was performed by real-time PCR, western
blot, and immunofluorescence. Our data showed that BTZ treatment significantly
reduced cell viability when compared to untreated cultures (about 40%).
Interestingly, ALA significantly reduced the efficacy of BTZ (about 30%).
Furthermore, BTZ significantly induced heme oxygenase-1 as a result of increased
oxidative stress and such overexpression was prevented by concomitant treatment
with ALA. Similarly, ALA significantly reduced BTZ-mediated endoplasmic reticulum
stress as measured by reduction in BiP1 and IRE1alpha, ERO1alpha, and PDI
expression. In conclusion, our data suggest that BTZ efficacy is dependent on
cellular redox status and such mechanisms may be responsible of chemoresistance
to this chemotherapeutic agent.
PMID- 28497203
TI - Retraction Note to: The Clinical Implications of Human Telomerase Reverse
Transcriptase Expression in Grade and Prognosis of Gliomas: a Systematic Review
and Meta-analysis.
PMID- 28497201
TI - Huntington Disease as a Neurodevelopmental Disorder and Early Signs of the
Disease in Stem Cells.
AB - Huntington disease (HD) is a dominantly inherited disorder caused by a CAG
expansion mutation in the huntingtin (HTT) gene, which results in the HTT protein
that contains an expanded polyglutamine tract. The adult form of HD exhibits a
late onset of the fully symptomatic phase. However, there is also a long
presymptomatic phase, which has been increasingly investigated and recognized as
important for the disease development. Moreover, the juvenile form of HD, evoked
by a higher number of CAG repeats, resembles a neurodevelopmental disorder and
has recently been the focus of additional interest. Multiple lines of data, such
as the developmental necessity of HTT, its role in the cell cycle and
neurogenesis, and findings from pluripotent stem cells, suggest the existence of
a neurodevelopmental component in HD pathogenesis. Therefore, we discuss the
early molecular pathogenesis of HD in pluripotent and neural stem cells, with
respect to the neurodevelopmental aspects of HD.
PMID- 28497204
TI - The biology and the importance of Photobacterium species.
AB - Photobacterium species are Gram-negative coccobacilli which are distributed in
marine habitats worldwide. Some species are unique because of their capability to
produce luminescence. Taxonomically, about 23 species and 2 subspecies are
validated to date. Genomes from a few Photobacterium spp. have been sequenced and
studied. They are considered a special group of bacteria because some species are
capable of producing essential polyunsaturated fatty acids, antibacterial
compounds, lipases, esterases and asparaginases. They are also used as biosensors
in food and environmental monitoring and detectors of drown victim, as well as an
important symbiont.
PMID- 28497205
TI - Transmission electron microscopy artifacts in characterization of the
nanomaterial-cell interactions.
AB - We investigated transmission electron microscopy artifacts obtained using
standard sample preparation protocols applied to the investigation of Escherichia
coli cells exposed to common nanomaterials, such as TiO2, Ag, ZnO, and MgO. While
the common protocols for some nanomaterials result only in known issues of
nanomaterial-independent generation of anomalous deposits due to fixation and
staining, for others, there are reactions between the nanomaterial and chemicals
used for post-fixation or staining. Only in the case of TiO2 do we observe only
the known issues of nanomaterial-independent generation of anomalous deposits due
to exceptional chemical stability of this material. For the other three
nanomaterials, different artifacts are observed. For each of those, we identify
causes of the observed problems and suggest alternative sample preparation
protocols to avoid artifacts arising from the sample preparation, which is
essential for correct interpretation of the obtained images and drawing correct
conclusions on cell-nanomaterial interactions. Finally, we propose modified
sample preparation and characterization protocols for comprehensive and
conclusive investigations of nanomaterial-cell interactions using electron
microscopy and for obtaining clear and unambiguous revelation whether the
nanomaterials studied penetrate the cells or accumulate at the cell membranes. In
only the case of MgO and ZnO, the unambiguous presence of Zn and Mg could be
observed inside the cells.
PMID- 28497206
TI - [Current status of teaching in lung ultrasound : Query of knowledge, utilization,
need, and preferred teaching method].
AB - BACKGROUND: Lung ultrasound (LUS) is a point-of-care technique which can quickly
identify or rule out pathological findings. To date, it is unclear if knowledge
about the use of LUS is readily available. OBJECTIVES: We aimed to identify how
much knowledge about the use of LUS is present, if there is a need for teaching
in LUS, as well as the preferred teaching method in LUS. MATERIALS AND METHODS: A
total of 54 participants from two university departments of anesthesiology were
randomized into the groups Online, Classroom, and Control. The Online group was
taught by videos, the Classroom group by a traditional lecture with hands-on
training, and the Control group was not taught at all. We conducted a pre- and
posttest as well as a retention test 4 weeks after the end of the study by means
of a survey (comparison with Mann-Whitney U test or t-test, respectively, with p
< 0.05 considered to be significant). RESULTS: LUS is used "rarely" or "never",
and mainly if there is a suspicion for pleural effusion (41.3%). There is a need
for LUS (Online: 21.7%; Classroom: 60.9%; Control: 62.5%, p < 0.05). Hybrid
teaching consisting of classroom-based and online-based teaching is preferred by
the users (Online: 52.2%; Classroom: 56.5%; Control: 62.5%). At the end of the
study, 32.6% of the participants of the intervention groups had used LUS in the
diagnosis of a pneumothorax. Of the participants, 93.5% planned to use LUS more
often in the future. CONCLUSIONS: LUS is rarely used. There is a considerable
need for teaching of LUS. Internet-based teaching and traditional lectures are
considered equal. Both teaching methods improve the knowledge about LUS and lead
to increased use of LUS in daily practice. The participants prefer hybrid
teaching incorporating both teaching methods.
PMID- 28497207
TI - Evaluation of rumen-protected choline additive to diet on productive performance
of male Zaraibi growing goats during hot summer season in Egypt.
AB - Twenty Zaraibi goat bucks were used in this experiment which lasted 3 months
during summer season of Egypt. The animals were divided randomly into two equal
groups. The first group was kept without treatment as control while in the second
group, rumen-protected choline (RPC) at the level of 20 g/buck/day was added to
the concentrate feed mixture at the morning feeding. RPC additives to diet of
Zaraibi goat bucks during the period of hot summer season increased (P < 0.01)
total gain and average daily gain compared to the control group. RPC increased (P
< 0.05) dry matter intake and feed conversion while water intake was not affected
by RPC additives. RPC increased (P < 0.05) red and white blood cell (RBC * 106,
WBC * 103) counts and hemoglobin concentration and hematocrit percentage. RPC
increased total protein (P < 0.05), globulin, and gamma-globulin (P < 0.01). On
the other hand, total lipids, total cholesterol, and triglyceride concentrations
decreased (P < 0.05 and P < 0.05) while phospholipids, glucose, and choline
concentrations increased (P < 0.01) due to RPC supplementation. RPC increased (P
< 0.01) thyroxin and triiodothyronine, increased (P < 0.05) testosterone levels,
and decreased (P < 0.01) cortisol level compared with control bucks. It is
concluded that dietary RPC at the rate of 20 g daily is required for growing male
goats, especially, under heat stress conditions of summer season in Egypt and
showed the best results concerning the growth, feed conversion, blood
metabolites, and economic efficiency.
PMID- 28497202
TI - Exosomes and their Application in Biomedical Field: Difficulties and Advantages.
AB - The science of gene therapy has experienced a controversial history. At first,
the initial concept that various disorders become curable by gene transferring
was very exciting and challengeable. However, the problems and difficulties
related to emerging techniques and unwanted side effects seen in some patients
who have undergone gene therapy make some questions against the safety of novel
molecular medicine approach. In line with this statement, discovery and
developing a good bio-vector possessing low toxicity and high efficiency rate are
the most important issues in gene therapy field. Introducing exosomes as vectors
for gene delivery gives us a new opportunity in gene-based therapy. Exosomes,
ranging from 30 to 120 nm in diameter, have unique lipid and protein composition.
These nanostructures participate in cell-to-cell cross-talk, regulation of immune
system, and the transport of genetic material. Besides the inherent potency of
exosomes in gene therapy, a better understanding of their biology,
characteristics, production, targeting, and cargo loading still need to be
elucidated. In the current review, we exclusively focused on the various facets
of exosomes and their importance as a bio-shuttle in gene therapy.
PMID- 28497208
TI - The Detrimental Effects of Adolescents' Chronic Loneliness on Motivation and
Emotion Regulation in Social Situations.
AB - In adolescence, when establishing and maintaining satisfying social relationships
is a key developmental task, chronic loneliness is related to a host of negative
outcomes. This study aimed at examining motivational and regulatory factors
related to chronic loneliness. Specifically, this study investigated chronically
lonely adolescents' responses to hypothetical vignettes of social inclusion and
exclusion, thereby focusing on (a) adolescents' willingness and motivation to
approach social inclusion and (b) emotion regulation strategies to deal with
social exclusion. A total of 730 adolescents (Mage = 15.43 years, 72% female)
participated in this four-wave study with annual loneliness assessments and
hypothetical vignettes of social inclusion and exclusion at the final wave. After
each social inclusion vignette, participants rated their willingness to accept
the invitation for social inclusion and five types of motivation to approach the
situation. After each social exclusion vignette, participants rated nine
cognitive emotion regulation strategies. Compared to individuals following other
trajectories, chronically lonely adolescents were less likely to accept
invitations for social inclusion and the quality of their motivation for
accepting such invitations was lower. Further, they were more likely to employ
maladaptive emotion regulation strategies. In sum, this study adds significantly
to understanding the motivational and regulatory processes that differentiate
chronically lonely adolescents from adolescents following other trajectories.
PMID- 28497209
TI - Pharmacists' perspectives of the current status of pediatric asthma management in
the U.S. community pharmacy setting.
AB - Objective To explore community pharmacists' continuing education, counseling and
communication practices, attitudes and barriers in relation to pediatric asthma
management. Setting Community pharmacies in Michigan, United States. Methods
Between July and September 2015 a convenience sample of community pharmacists was
recruited from southeastern Michigan and asked to complete a structured, self
reported questionnaire. The questionnaire elucidated information on 4 general
domains relating to pharmacists' pediatric asthma management including: (1)
guidelines and continuing education (CE); (2) counseling and medicines; (3)
communication and self-management practices; (4) attitudes and barriers to
practice. Regression analyses were conducted to determine predictors towards
pharmacists' confidence/frequency of use of communication/counseling strategies.
Main outcome measure Confidence in counseling skills around asthma. Results 105
pharmacists completed the study questionnaire. Fifty-four percent of pharmacists
reported participating in asthma related CE in the past year. Over 70% of
pharmacists reported confidence in general communication skills, while a lower
portion reported confidence in engaging in higher order self-management
activities that involved tailoring the regimen (58%), decision-making (50%) and
setting short-term (47%) and long-term goals (47%) with the patient and caregiver
for managing asthma at home. Pharmacists who reported greater use of recommended
communication/self-management strategies were more likely to report confidence in
implementing these communication/self-management strategies when counseling
caregivers and children with asthma [Beta (B) Estimate 0.58 SE (0.08), p <
0.001]. Female pharmacists [B Estimate -2.23 SE (1.01), p < 0.05] and those who
reported beliefs around doctors being the sole provider of asthma education [B
Estimate -1.00 SE (0.32), p < 0.01] were less likely to report confidence in
implementing communication/self-management strategies. Conclusion A pharmacists'
confidence may influence their ability to implement recommended self-management
counseling strategies. This study showed that community pharmacists are confident
in general communication. However pharmacists are reporting lower confidence
levels in counseling on higher order self-management strategies with patients.
More appropriate and targeted continuing education programs for pharmacists
around asthma self-management education are recommended.
PMID- 28497210
TI - Genetic Characterization of Influenza A (H1N1) Pandemic 2009 Virus Isolates from
Mumbai.
AB - Pandemic influenza A (H1N1) 2009 virus was first detected in India in May 2009
which subsequently became endemic in many parts of the country. Influenza A
viruses have the ability to evade the immune response through its ability of
antigenic variations. The study aims to characterize influenza A (H1N1) pdm 09
viruses circulating in Mumbai during the pandemic and post-pandemic period.
Nasopharyngeal swabs positive for influenza A (H1N1) pdm 09 viruses were
inoculated on Madin-Darby canine kidney cell line for virus isolation. Molecular
and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates was conducted to
understand the evolution and genetic diversity of the strains. Nucleotide and
amino acid sequences of the HA gene of Mumbai isolates when compared to
A/California/07/2009-vaccine strain revealed 14 specific amino acid differences
located at the antigenic sites. Amino acid variations in HA and NA gene resulted
in changes in the N-linked glycosylation motif which may lead to immune evasion.
Phylogenetic analysis of the isolates revealed their evolutionary position with
vaccine strain A/California/07/2009 but had undergone changes gradually. The
findings in the present study confirm genetic variability of influenza viruses
and highlight the importance of continuous surveillance during influenza
outbreaks.
PMID- 28497211
TI - Association of toll-like receptor gene polymorphisms and its interaction with HPV
infection in determining the susceptibility of cervical cancer in Chinese Han
population.
AB - The aim of the study is to investigate the association of several single
nucleotide polymorphisms (SNPs) within Toll-like receptors (TLRs) gene and
additional gene-gene and gene-human papillomavirus (HPV) infection interaction
with cervical cancer risk. A total of 1262 participants are selected, including
420 cervical cancer patients and 842 control participants. Generalized
multifactor dimensionality reduction (GMDR) was used to screen the best
interaction combination among five SNPs within TLR gene and HPV infection.
Logistic regression was performed to calculate the ORs (95 %CI) for association
of five SNPs within TLR gene and additional gene-HPV infection interaction with
cervical cancer risk. Cervical cancer risk was significantly higher in carriers
of the T allele of rs3775290 within TLR2 gene, the G allele of rs7873784 within
TLR4 gene, and the A allele of rs352140 within TLR9 gene than those with wild
genotype; adjusted ORs (95 %CI) were 1.78 (1.20-2.24), 1.65 (1.23-2.12), and 1.70
(1.16-2.31). However, we did not find any significant association of rs4986791
and rs11536889 with cervical cancer risk. GMDR analysis suggested a significant
two-locus model (p = 0.0107) involving rs352140 and HPV infection. Subjects with
HPV infection and rs352140-GA + AA genotype within TLR9 gene have the highest
cervical cancer risk, compared to no HPV infection participants with rs352140-GG
genotype, OR (95 %CI) = 3.22 (1.68-4.81). Pairwise LD analysis did not find any
significant haplotype combination associated with cervical cancer risk. The minor
alleles of TLR2-rs3775290, TLR4-rs7873784, and TLR9-rs352140, and interaction
between rs352140 and HPV infection were all associated with increased cervical
cancer risk.
PMID- 28497212
TI - Renal Osteodystrophy or Kidney-Induced Osteoporosis?
AB - PURPOSE OF REVIEW: Chronic kidney disease (CKD) affects nearly 10% of the
population. The incidence of fractures in population studies demonstrate an
increase with worsening stages of kidney disease suggesting specific CKD related
causes of fracture. RECENT FINDINGS: The increase in fractures with CKD most
likely represents disordered bone quality due to the abnormal bone remodeling
from renal osteodystrophy. There is also an increase in fractures with age in
patients with CKD, suggesting that patients with CKD also have many fracture risk
factors common to patients without known CKD. Osteoporosis is defined by the
National Institutes of Health as "A skeletal disorder characterized by
compromised bone strength predisposing to an increased risk of fracture. Bone
strength reflects the integration of two main features: bone quantity and bone
quality." Thus, CKD-related fractures can be considered a type of osteoporosis
where the bone quality is additionally impaired above that of age/hormonal
related osteoporosis. Perhaps using the term CKD-induced osteoporosis, similar to
steroid-induced osteoporosis, will allow patients with CKD to be studied in
trials investigating therapeutic agents. In this series, we will examine how CKD
induced osteoporosis may be diagnosed and treated.
PMID- 28497214
TI - Comparative theoretical studies of differently bridged nitramino-substituted
ditetrazole 2-N-oxides with high detonation performance and an oxygen balance of
around zero.
AB - In this work, six (A-F) nitramino (-NHNO2)-substituted ditetrazole 2-N-oxides
with different bridging groups (-CH2-, -CH2-CH2-, -NH-, -N=N-, and -NH-NH-) were
designed. The six compounds were based on the parent compound tetrazole 2-N
oxide, which possesses a high oxygen balance and high density. The structure,
heat of formation, density, detonation properties (detonation velocity D and
detonation pressure P), and the sensitivity of each compound was investigated
systematically via density functional theory, by studying the electrostatic
potential, and using molecular mechanics. The results showed that compounds A-F
all have outstanding energetic properties (D: 9.1-10.0 km/s; P: 38.0-46.7 GPa)
and acceptable sensitivities (h 50: 28-37 cm). The bridging group present was
found to greatly affect the detonation performance of each ditetrazole 2-N-oxide,
and the compound with the -NH-NH- bridging group yielded the best results.
Indeed, this compound (F) was calculated to have comparable sensitivity to the
famous and widely used high explosive 1,3,5,7-tetranitro-1,3,5,7-tetrazocane
(HMX), but with values of D and P that were about 8.7% and 19.4% higher than
those for HMX, respectively. The present study shows that tetrazole 2-N-oxide is
a useful parent compound which could potentially be used in the design of new and
improved high-energy compounds to replace existing energetic compounds such as
HMX.
PMID- 28497213
TI - Bone Pain and Muscle Weakness in Cancer Patients.
AB - PURPOSE OF REVIEW: In this article, we will discuss the current understanding of
bone pain and muscle weakness in cancer patients. We will describe the underlying
physiology and mechanisms of cancer-induced bone pain (CIBP) and cancer-induced
muscle wasting (CIMW), as well as current methods of diagnosis and treatment. We
will discuss future therapies and research directions to help patients with these
problems. RECENT FINDINGS: There are several pharmacologic therapies that are
currently in preclinical and clinical testing that appear to be promising
adjuncts to current CIBP and CIMW therapies. Such therapies include
resiniferitoxin, which is a targeted inhibitor of noceciptive nerve fibers, and
selective androgen receptor modulators, which show promise in increasing lean
mass. CIBP and CIMW are significant causes of morbidity in affected patients.
Current management is mostly palliative; however, targeted therapies are poised
to revolutionize how these problems are treated.
PMID- 28497216
TI - Genome characterization of sweet potato symptomless virus 1: a mastrevirus with
an unusual nonanucleotide sequence.
AB - Complete genomic sequences of nine isolates of sweet potato symptomless virus 1
(SPSMV-1), a virus of the genus Mastrevirus in the family Geminiviridae, were
determined from sweet potato accessions from different countries and found to be
2,559-2,602 nucleotides in length. These isolates shared 97-100% genome sequence
identity and had an unusual nonanucleotide sequence (TAAGATTCC) in a large
intergenic region as well as an additional open reading frame, C3, which is
conserved in dicot-infecting mastreviruses.
PMID- 28497215
TI - Evidence-based prevention and treatment of osteoporosis after spinal cord injury:
a systematic review.
AB - PURPOSE: Spinal cord injury (SCI) results in accelerated bone mineral density
(BMD) loss and disorganization of trabecular bone architecture. The mechanisms
underlying post-SCI osteoporosis are complex and different from other types of
osteoporosis. Findings of studies investigating efficacy of pharmacological or
rehabilitative interventions in SCI-related osteoporosis are controversial. The
aim of this study was to review the literature pertaining to prevention and
evidence-based treatments of SCI-related osteoporosis. METHODS: In this
systematic review, MEDLINE, EMBASE, PubMed, and the Cochrane Library were used to
identify papers from 1946 to December 31, 2015. The search strategy involved the
following keywords: spinal cord injury, osteoporosis, and bone loss. RESULTS:
Finally, 56 studies were included according to the inclusion criteria. Only 16
randomized controlled trials (involving 368 patients) were found. We found
following evidences for effectiveness of bisphosphonates in prevention of BMD
loss in acute SCI: very low-quality evidence for clodronate and etidronate, low
quality evidence for alendronate, and moderate-quality evidence for zoledronic
acid. Low-quality evidence showed no effectiveness for tiludronate. In chronic
SCI cases, we found low-quality evidence for effectiveness of vitamin D3 analogs
combined with 1-alpha vitamin D2. However, low-quality inconsistent evidence
exists for alendronate. For non-pharmacologic interventions, very low-quality
evidence exists for effectiveness of standing with or without treadmill walking
in acute SCI. Other low-quality evidences indicated that electrical stimulation,
tilt-table standing, and ultrasound provide no significant effects. Very low
quality evidence did not show any benefit for low-intensity (3 days per week)
cycling with functional electrical stimulator in chronic SCI. CONCLUSIONS: No
recommendations can be made from this review, regarding overall low quality of
evidence as a result of high risk of bias, low sample size in most of the
studies, and notable heterogeneity in type of intervention, outcome measurement,
and duration of treatment. Therefore, future high-quality RCT studies with higher
sample sizes and more homogeneity are strongly recommended to provide high
quality evidence and make applicable recommendations for prevention and treatment
of SCI-related bone loss.
PMID- 28497217
TI - Inhibition of Clostridium difficile in Mice Using a Mixture of Potential
Probiotic Strains Enterococcus faecalis NM815, E. faecalis NM915, and E. faecium
NM1015: Novel Candidates to Control C. difficile Infection (CDI).
AB - This study is aimed at the isolation, identification, and characterization of
potential probiotic strains capable of inhibiting Clostridium difficile in vitro
and in vivo. Twenty isolates were isolated from infant fecal samples and screened
against C. difficile using their cell-free supernatant. Only three isolates
showed maximum inhibition from 56.05 to 60.60%, thus they were characterized for
probiotic properties and safety. The results obtained approved their tolerance to
the gastrointestinal tract conditions and safety profile. They were identified by
sequencing 16S rRNA as Enterococcus faecalis NM815, E. faecalis NM915, and
Enterococcus faecium NM1015. For in vivo evaluation, a viable mixture of these
three strains (109 CFU/mL) was administrated to a group of mice (treated group)
in daily dose for 14 days, then followed by challenge with viable C. difficile
(105 CFU/mL) in daily dose for 7 days, then a second administration of a viable
mixture of the three strains was done daily for 7 days. In addition, the control
group was administered PBS buffer only and the untreated group received PBS
buffer instead of the probiotic mixture before and after the challenge with C.
difficile. The results obtained from histological analysis confirmed the
effectiveness of our three potential probiotic strains which expressed inhibition
of C. difficile and maintained the structural integrity of the liver and
intestinal cells.
PMID- 28497218
TI - To evaluate the efficacy of an acellular Flowable matrix in comparison with a wet
dressing for the treatment of patients with diabetic foot ulcers: a randomized
clinical trial.
AB - The authors aimed to evaluate the efficacy of an advanced wound matrix (Integra
Flowable Wound Matrix, Integra LifeScience Corp, Plainsboro, NJ, USA) for
treating wounds with irregular geometries versus a wet dressing in patients with
diabetic foot ulcers. Sixty patients with diabetic foot ulcers (Grades 3 Wagner)
were included in this randomized clinical trial. The study was conducted in the
General Surgery Unit and Geriatric of the Second University of Naples, Italy, in
the last 12 months. Forty-six cases of diabetic foot ulcers were equally and
randomly divided into control and test groups. The first group treated with
Integra Flowable Wound Matrix, while the control group with a wet dressing. Both
groups were evaluated once a week for 6 weeks to value the degree of
epithelialization and granulation tissue of the wound. The complete healing rate
in the whole study population was 69.56% (Integra Flowable Wound Matrix group,
86.95%, control group, 52.17%; p = 0.001). Amputation and rehospitalization rates
were higher in the control group compared to the first group, therefore, the
difference was statistically significant (p = 0.0019; p = 0.028, respectively).
The Integra Flowable Wound Matrix, was significantly superior, compared to the
wet dressing, by promoting the complete healing of diabetic foot ulcers. Ease of
use, absence of adverse effects, and a facilitated wound healing process are
among the properties of the matrix. These characteristics make it appropriate in
the management of diabetic foot ulcers. Additional research will shed more light
on the promising advantages of this material in healing diabetic foot ulcers.
PMID- 28497220
TI - CT-P10 (TruximaTM): A Rituximab Biosimilar.
AB - CT-P10 (TruximaTM) is the first biosimilar of the reference monoclonal anti-CD20
antibody rituximab. It is approved for use in all indications for which reference
rituximab is approved, including follicular lymphoma (FL), diffuse large B-cell
non-Hodgkin's lymphoma, chronic lymphocytic leukaemia, rheumatoid arthritis (RA),
granulomatosis with polyangiitis and microscopic polyangiitis. CT-P10 has similar
physicochemical and pharmacodynamic properties to those of reference rituximab,
and the pharmacokinetic biosimilarity of the agents has been shown in patients
with RA or FL. CT-P10 demonstrated clinical efficacy equivalent to that of
reference rituximab in patients with RA, and was generally well tolerated in this
population as well as in patients with FL. The tolerability, immunogenicity and
safety profiles of CT-P10 were similar to those of reference rituximab, and
switching from reference rituximab to CT-P10 had no impact on safety or efficacy.
The role of reference rituximab in the management of autoimmune conditions and
cancers is well established and CT-P10 provides an effective biosimilar
alternative for patients requiring rituximab therapy.
PMID- 28497219
TI - Robot-assisted adrenalectomy: indications and drawbacks.
AB - Adrenal tumors can vary from a benign adrenocortical adenoma with no hormonal
secretion to a secretory adrenocortical malignancy (adrenocortical carcinoma) or
a hormone-secreting tumor of the adrenal medulla (pheochromocytoma). Currently,
laparoscopic adrenalectomy is regarded as the preferred surgical approach for the
management of most adrenal surgical disorders, although there are no prospective
randomized trials comparing this technique with open adrenalectomy. However,
widespread adoption of robotic technology has positioned robotic adrenalectomy as
an option in some medical centers. Speculative advantages associated with the use
of the robotic system have rarely been evaluated in clinical settings and cost
increase remains an important drawback associated with robotic surgery. This
review summarizes current available data regarding robotic transperitoneal
adrenalectomy including its indications, advantages, limitations, and comparison
with conventional laparoscopic adrenalectomy. We believe that the use of a
robotic system seems to be useful especially in more difficult patients with
larger tumors, truncal paragangliomas, and bilateral and/or partial
adrenalectomies. Overall, we believe that overcosts due to robotic system use
could be balanced by hospital stay decrease, patients' referral increase,
improved postoperative outcomes in more difficult patients and ergonomics for the
surgeon. However, we also believe that the current surgical intuitive business
model is counterproductive, because there are no available strong clinical data
that could balance overcosts associated with the use of the robotic system.
PMID- 28497221
TI - Evaluation of the Cross-reactivity of Antidrug Antibodies to CT-P13 and
Infliximab Reference Product (Remicade): An Analysis Using Immunoassays Tagged
with Both Agents.
AB - BACKGROUND: During two pivotal clinical trials of the infliximab biosimilar CT
P13 (PLANETAS and PLANETRA), antidrug antibodies (ADAs) and neutralising
antibodies (NAbs) were detected in the sera of patients treated with CT-P13 and
the reference product (RP; Remicade). OBJECTIVE: The aim was to assess the
comparability of Remicade- and CT-P13-tagged immunoassays for the detection of
ADAs and NAbs using data from these trials, in order to determine the cross
reactivity of CT-P13 and RP ADAs. METHODS: Sera from patients with rheumatoid
arthritis and ankylosing spondylitis were analysed using an
electrochemiluminescence (ECL) bridging assay or Gyros immunoassay, tagged with
Remicade or CT-P13 at screening, weeks 14, 30 and 54, and the end of study visit.
NAb titre was compared at screening and weeks 14 and 30. The proportion of cross
reactive samples was determined and an inter-rater agreement analysis performed
to assess the concordance of results between assays. RESULTS: In PLANETAS, 93.1%
(94/101) of RP ADA-positive samples and 93.0% (93/100) of RP NAb-positive samples
cross-reacted with CT-P13; 99.0% (103/104) of CT-P13 ADA-positive and 98.0%
(98/100) of CT-P13 NAb-positive samples cross-reacted with the RP. In PLANETRA,
94.7% (426/450) of RP ADA-positive samples and 94.3% (415/440) of RP NAb-positive
samples cross-reacted with CT-P13, and 96.6% (458/474) of CT-P13 ADA-positive and
96.4% (452/469) of CT-P13 NAb-positive samples cross-reacted with the RP. In both
studies, there was strong agreement in outcome between assays at all post
screening time points (PLANETAS: Cohen's kappa 0.89-0.98 for ADA, 0.86-0.98 for
NAb; PLANETRA: 0.92-0.94 for both ADA and NAb, all p < 0.001). Significant
concordance between assays was observed for NAb titre at weeks 14 and 30
(PLANETAS: Spearman's rho 0.73 and 0.74, respectively; PLANETRA: 0.61 and 0.72,
respectively; all p < 0.001). CONCLUSIONS: This study has demonstrated that ADAs
and NAbs against CT-P13 and RP are cross-reactive, indicating that CT-P13 and RP
share immunodominant epitopes.
PMID- 28497222
TI - Interleukin-1 Blockade: An Update on Emerging Indications.
AB - Interleukin (IL)-1 is a pro-inflammatory cytokine that induces local and systemic
inflammation aimed to eliminate microorganisms and tissue damage. However, an
increasing number of clinical conditions have been identified in which IL-1
production is considered inappropriate and IL-1 is part of the disease etiology.
In autoinflammatory diseases, gout, Schnitzler's syndrome, and adult-onset
Still's disease, high levels of inappropriate IL-1 production have been shown to
be a key process in the etiology of the disease. In these conditions, blocking IL
1 has proven very effective in clinical studies. In other diseases, IL-1 has
shown to be present in disease process but is not the central driving force of
inflammation. In these conditions, including type 1 and 2 diabetes mellitus,
acute coronary syndrome, amyotrophic lateral sclerosis, and several neoplastic
diseases, the benefits of IL-1 blockade are minimal or absent.
PMID- 28497223
TI - Successful endovascular treatment of popliteal artery entrapment syndrome: a case
report with 3-years follow-up.
AB - Popliteal artery entrapment syndrome (PAES) is a rare cause of lower extremity
arterial ischemia, especially in elder patients. At present, the role of the
endovascular technique for PAES is still mainly auxiliary, there is no successful
case treated successfully by endovascular treatment without open surgery, and
also the long-term follow-up after endovascular treatment are lacking. We
successfully treated a 51-year-old man with pale, cold right foot by endovascular
therapy only, including percutaneous transluminal angioplasty and catheter
directed thrombolysis. After endovascular treatment, the ABI of the right leg
increased from 0.41 to 0.85, and the patient return to his life without
claudication. Computed tomography angiography demonstrated the diagnosis of PAES.
The 3-year follow-up showed a good clinical outcome, suggesting that for certain
type of PAES, endovascular treatment alone may achieve good results. However,
this result still requires confirmation in a large-sample study.
PMID- 28497224
TI - Bone density, microarchitecture, and material strength in chronic kidney disease
patients at the time of kidney transplantation.
AB - : Bone health is assessed by bone mineral density (BMD). Other techniques such as
trabecular bone score and microindentation could improve the risk of fracture's
estimation. Our chronic kidney disease (CKD) patients presented worse bone health
(density, microarchitecture, mechanical properties) than controls. More than BMD
should be done to evaluate patients at risk of fracture. INTRODUCTION: BMD
measured by dual-energy X-ray absorptiometry (DXA) is used to assess bone health
in end-stage renal disease (ESRD) patients. Recently, trabecular bone score (TBS)
and microindentation that can measure microarchitectural and mechanical
properties of bone have demonstrated better correlation with fractures than DXA
in different populations. We aimed to characterize bone health (BMD, TBS, and
strength) and calcium/phosphate metabolism in a cohort of 53 ESRD patients
undergoing kidney transplantation (KT) and 94 controls with normal renal
function. METHODS: Laboratory workout, lumbar spine/hip BMD measurements (using
DXA), lumbar spine TBS, and bone strength were carried out. The latter was
assessed with an impact microindentation device, standardized as percentage of a
reference value, and expressed as bone material strength index (BMSi) units.
Multivariable linear regression was used to study differences between cases and
controls adjusted by age, gender, and body mass index. RESULTS: Among cases,
serum calcium was 9.6 +/- 0.7 mg/dl, phosphorus 4.4 +/- 1.2 mg/dl, and intact
parathyroid hormone 214 pg/ml [102-390]. Fourteen patients (26.4%) had prevalent
asymptomatic fractures in spinal X-ray. BMD was significantly lower among ESRD
patients compared to controls: lumbar 0.966 +/- 0.15 vs 0.982 +/- 0.15 (adjusted
p = 0.037), total hip 0.852 +/- 0.15 vs 0.902 +/- 0.13 (adjusted p < 0.001), and
femoral neck 0.733 +/- 0.15 vs 0.775 +/- 0.12 (adjusted p < 0.001), as were TBS
(1.20 [1.11-1.30] vs 1.31 [1.19-1.43] (adjusted p < 0.001)) and BMSi (79 [71.8
84.2] vs 82. [77.5-88.9] (adjusted p = 0.005)). CONCLUSIONS: ESRD patients
undergoing transplant surgery have damaged bone health parameters (density,
microarchitecture, and mechanical properties) despite acceptably controlled
hyperparathyroidism. Detecting these abnormalities may assist in identifying
patients at high risk of post-transplantation fractures.
PMID- 28497225
TI - Development of a rapid HRM qPCR for the diagnosis of the four most prevalent
Plasmodium lineages in New Zealand.
AB - Although wildlife rehabilitation and translocations are important tools in
wildlife conservation in New Zealand, disease screening of birds has not been
standardized. Additionally, the results of the screening programmes are often
difficult to interpret due to missing disease data in resident or translocating
avian populations. Molecular methods have become the most widespread method for
diagnosing avian malaria (Plasmodium spp.) infections. However, these methods can
be time-consuming, expensive and are less specific in diagnosing mixed
infections. Thus, this study developed a new real-time PCR (qPCR) method that was
able to detect and specifically identify infections of the three most common
lineages of avian malaria in New Zealand (Plasmodium (Novyella) sp. SYAT05,
Plasmodium elongatum GRW6 and Plasmodium spp. LINN1) as well as a less common,
pathogenic Plasmodium relictum GRW4 lineage. The assay was also able to discern
combinations of these parasites in the same sample and had a detection limit of
five parasites per microlitre. Due to concerns relating to the presence of the
potentially highly pathogenic P. relictum GRW4 lineage in avian populations, an
additional confirmatory high resolution (HRM) qPCR was developed to distinguish
between commonly identified P. elongatum GRW6 from P. relictum GRW4. The new qPCR
assays were tested using tissue samples containing Plasmodium schizonts from
three naturally infected dead birds resulting in the identified infection of P.
elongatum GRW6. Thus, these rapid qPCR assays have shown to be cost-effective and
rapid screening tools for the detection of Plasmodium infection in New Zealand
native birds.
PMID- 28497226
TI - Anisakis haemoglobin is a main antigen inducing strong and prolonged
immunoreactions in rats.
AB - Anisakis simplex larvae are well known to cause gastrointestinal and allergic
manifestations after ingestion of parasitized raw or undercooked seafood. The
antibody recognition dynamics against the components of Anisakis larval antigen
after primary and re-infection with Anisakis live larvae remain unclear. For this
study, immunoblot analyses of serum IgG, IgE, and IgM against Anisakis larval
somatic extract were performed in rats that had been orally inoculated with A.
simplex live larvae. Multiple antigen fractions were recognized after primary
infection. Their reaction was enhanced after re-infection. Antibody recognition
was observed for 12 weeks after re-infection. The fraction of approximately 35
kDa contained a main antigen that induced strong and prolonged immunoreactions in
IgG and IgE. The antibody reaction to this fraction appeared to be enhanced after
inoculation of larval homogenates. This fraction was heat tolerant with boiling
for 30 min. The fraction was spotted by immunoblotting after two-dimensional
electrophoresis and was identified as Anisakis haemoglobin (Ani s 13) using mass
spectrometry analysis. The amino acid sequences of haemoglobin mRNAs from two A.
simplex sensu stricto and one Anisakis pegreffii were identified by RACE-PCR.
They differed from those of two isolates of Pseudoterranova decipiens and A.
pegreffii. Results of this study show that Anisakis haemoglobin, which is known
to be a major allergen of A. simplex, induces strong and prolonged immunoreaction
in rats. This report is the first to show the amino acid sequence variation of
Anisakis haemoglobin mRNA between A. simplex sensu stricto and A. pegreffii.
PMID- 28497227
TI - Seroprevalence of Neospora caninum and Toxoplasma gondii in exotic ruminants and
camelids in the Czech Republic.
AB - Neospora caninum and Toxoplasma gondii are the protozoan parasites with
definitive hosts from order Carnivora. Due to vertical transmission, both
parasites can cause abortions and neonatal mortality that lead to significant
productive and economic losses in the domestic ruminants. The aim of this study
was to describe N. caninum and T. gondii seroprevalence in the group of
frequently farmed captive exotic ruminants (n = 184) including Bovidae (barbary
sheep, bezoar goat, common eland, American bison, water buffalo, and yak) and
Camelidae (bactrian camel, guanaco, llama, and alpaca). Antibodies were tested by
indirect fluorescent antibody test (IFAT) and enzyme-linked immunosorbent assay
(ELISA). Higher prevalence of T. gondii antibodies (31% in IFAT and 52% in ELISA)
was detected compared to N. caninum (24% in IFAT and 17% in cELISA). Mixed
infection was found in 18 (10%) and 22 (12%) animals by IFAT and ELISA,
respectively. Higher seroprevalence of both N. caninum and T. gondii was found in
Camelidae compared to Bovidae. To author knowledge, this is the first detection
of T. gondii and N. caninum antibodies in common elands and bezoar goats.
PMID- 28497229
TI - In vitro assessment of arsenic mobility in historical mine waste dust using
simulated lung fluid.
AB - Exposure studies have linked arsenic (As) ingestion with disease in mining
affected populations; however, inhalation of mine waste dust as a pathway for
pulmonary toxicity and systemic absorption has received limited attention. A
biologically relevant extractant was used to assess the 24-h lung
bioaccessibility of As in dust isolated from four distinct types of historical
gold mine wastes common to regional Victoria, Australia. Mine waste particles
less than 20 um in size (PM20) were incubated in a simulated lung fluid
containing a major surface-active component found in mammalian lungs,
dipalmitoylphosphatidylcholine. The supernatants were extracted, and their As
contents measured after 1, 2, 4, 8 and 24 h. The resultant As solubility profiles
show rapid dissolution followed by a more modest increasing trend, with between
75 and 82% of the total 24-h bioaccessible As released within the first 8 h.
These profiles are consistent with the solubility profile of scorodite, a
secondary As-bearing phase detected by X-ray diffraction in one of the
investigated waste materials. Compared with similar studies, the cumulative As
concentrations released at the 24-h time point were extremely low (range 297 +/-
6-3983 +/- 396 ug L-1), representing between 0.020 +/- 0.002 and 0.036 +/- 0.003%
of the total As in the PM20.
PMID- 28497228
TI - 18-Des-hydroxy Cytochalasin: an antiparasitic compound of Diaporthe phaseolorum
92C, an endophytic fungus isolated from Combretum lanceolatum Pohl ex Eichler.
AB - Chemical investigation of the ethyl acetate extract from the endophytic fungus
Diaporthe phaseolorum-92C (92C) isolated from the roots of Combretum lanceolatum
led to the isolation of 18-des-hydroxy Cytochalasin H (compound 1). The
trypanocidal and schistosomicidal activity and cytotoxicity of the extract from
92C were evaluated. The schistosomicidal, leishmanicidal, antimicrobial, and
antioxidant actions, as well as the antitumor activity against the breast cancer
cells MDA-MB-231 and MCF-7, and the cytotoxicity towards normal human lung
fibroblasts GM07492A of compound 1 was tested. The extract from 92C (20 MUg/mL)
exerted potent trypanocidal activity, reducing 82% of the number of amastigotes
and trypomastigotes of Trypanosoma cruzi. Compound 1 at 50 MUg/mL killed 50% of
Schistosoma mansoni adult worms. Compound 1 reduced the viability of Leishmania
amazonenses promastigotes (IC50 = 9.2 MUg/mL) and of the cancer cells MDA-MB-231
and MCF-7 (IC50 = 17.5 and 8.88 MUg/mL, respectively), presented moderate
antioxidant activity, and gave IC50 of 2049.7 +/- 39.9 MUg/mL for the
cytotoxicity towards normal cells GM07492A. This knowledge is highly relevant to
the search for new promising compounds for therapeutic purposes.
PMID- 28497230
TI - Heart failure with preserved ejection fraction: a nephrologist-directed primer.
AB - There is substantial causal and consequential interaction between the ever
growing heart failure and renal failure patients. Half of the patients with heart
failure (HF) have preserved left ventricular ejection fraction (HFpEF), which is
difficult to diagnose and rising in prevalence relative to HF with reduced EF
(HFpEF). To date, only weight reduction, exercise training, and diuretics have
been shown to improve exercise tolerance and morbidity in HFpEF. This review aims
to establish the baseline kidney-related concepts specific to the diagnosis and
treatment of HFpEF patients and the different aspects of HFpEF and HFpEF in the
clinical setting.
PMID- 28497231
TI - T2 mapping and T2* imaging in heart failure.
AB - Cardiovascular magnetic resonance (CMR) is a versatile imaging modality that
enables aetiological assessment and provides additional information to that of
standard echocardiography in a significant proportion of patients with heart
failure. In addition to highly accurate and reproducible assessment of
ventricular volumes and replacement fibrosis, multiparametric mapping techniques
have rapidly evolved to further expand the diagnostic and prognostic applications
in various conditions ranging from acute inflammatory and ischaemic
cardiomyopathy, to cardiac involvement in systemic diseases such as sarcoidosis
and iron overload cardiomyopathy. In this review, we discuss the established role
of T2* imaging and rapidly evolving clinical applications of myocardial T2
mapping as quantitative adjuncts to established qualitative imaging techniques.
PMID- 28497232
TI - Tamoxifen for induction of Cre-recombination may confound fibrosis studies in
female mice.
AB - A variety of conditional knock-out mice relying on Tamoxifen-driven ERT2/Cre
mediated recombination are available and have been used to study involvement of
specific genes in kidney disease. However, recent data suggest that Tamoxifen
itself might attenuate fibrosis when administered during experimental models of
kidney disease. It has remained unclear whether this still applies also if kidney
damage is initiated after a wash-out period has been implemented. Here we report
that the commonly applied regimen of administration of 4 alternate day doses of
1mg Tamoxifen per mouse until 14 days prior to start of the actual experiment, in
this case the induction of obstructive nephropathy by Unilateral Ureteral
Obstruction (UUO), still attenuated fibrosis in female obstructed mouse kidneys,
whereas this effect was not seen in male obstructed kidneys. Attenuation of
fibrosis was accompanied by a reduction in nuclear ERalpha positivity despite
absence of detectable levels of the active tamoxifen metabolite endoxifen
throughout the UUO experiment. In conclusion, these results indicate that the
Tamoxifen dosing regimen commonly applied in conditional gene targeting
experiments might have prolonged confounding effects in female mice through
attenuation of renal fibrosis independent of modulation of the expression of the
targeted gene(s).
PMID- 28497234
TI - The 2017 CALDAR Summer Institute and International Conference Promoting Global
Health-Precision Research in Substance Abuse, HIV, and Care.
AB - The 2017 CALDAR Summer Institute on Longituidnal Research and International
Conference Series to Promote Global Health will take place in Los Angeles
Universal City, CA, USA from August 15 to August 17, 2017. The conference will
present a selection of the lastest and most current reseach in the areas of
addiction, HIV, and related treatment.
PMID- 28497233
TI - Standardization and Optimization of Intraoperative Molecular Imaging for
Identifying Primary Pulmonary Adenocarcinomas.
AB - PURPOSE: Intraoperative molecular imaging (IMI) is an emerging technology used to
locate pulmonary adenocarcinomas and identify positive margins during surgery.
Background noise and tissue autofluorescence have been major obstacles. The goal
of this study is to optimize the image quality of folate receptor alpha (FRalpha)
targeted IMI for pulmonary adenocarcinomas by modifying emission data.
PROCEDURES: A total of 15 lung cancer patients were enrolled in a pilot study. In
the first cohort, FRalpha upregulation within pulmonary adenocarcinoma tumors was
confirmed by analyzing specimens from five pulmonary adenocarcinoma patients with
flow cytometry and immunohistochemistry. Next, in a cohort of five additional
patients, autofluorescence of intrathoracic structures and tissues was
quantified. Lastly, five patients with tumors at various depths from the pleural
surface were enrolled and received the FRalpha-targeted optical contrast agent,
EC17. In this final cohort, resected pulmonary adenocarcinomas were imaged at a
wide range of fluorescence exposure times (0 to 200 ms), various laser powers,
and with unique filter configurations. Tumor-to-noise ratio (TNR) for images was
generated using region of interest software. RESULTS: Pulmonary adenocarcinomas
highly express FRalpha. Significant autofluorescence from native thoracic tissues
was found with the highest fluorescent signals at the bronchial stump (547 +/-
98, range 423-699), the pulmonary artery (267 +/- 64, range 200-374), and
cortical bone (266 +/- 17, range 243-287). High levels of autofluorescence were
appreciated after systemic administration of EC17; however, TNR was improved by
altering exposure settings at the time of the imaging. Optimal fluorescent
exposure time occurs at 40 ms (25 frames/s). CONCLUSIONS: Exposure properties can
be manipulated to maximize TNR thus allowing for successful intraoperative
detection of pulmonary adenocarcinomas during surgery. Optimization of the
conditions for intraoperative molecular imaging sets the stage for future
clinical trials utilizing targeted IMI techniques which can aid the surgeon at
the time of cancer resection.
PMID- 28497235
TI - Spatiotemporal Dynamics of the Cortical Responses Induced by a Prolonged Tactile
Stimulation of the Human Fingertips.
AB - The sense of touch is fundamental for daily behavior. The aim of this work is to
understand the neural network responsible for touch processing during a prolonged
tactile stimulation, delivered by means of a mechatronic platform by passively
sliding a ridged surface under the subject's fingertip while recording the
electroencephalogram (EEG). We then analyzed: (i) the temporal features of the
Somatosensory Evoked Potentials and their topographical distribution bilaterally
across the cortex; (ii) the associated temporal modulation of the EEG frequency
bands. Long-latency SEP were identified with the following physiological sequence
P100-N140-P240. P100 and N140 were bilateral potentials with higher amplitude in
the contralateral hemisphere and with delayed latency in the ipsilateral side.
Moreover, we found a late potential elicited around 200 ms after the stimulation
was stopped, which likely encoded the end of tactile input. The analysis of
cortical oscillations indicated an initial increase in the power of theta band (4
7 Hz) for 500 ms after the stimulus onset followed a decrease in the power of the
alpha band (8-15 Hz) that lasted for the remainder of stimulation. This decrease
was prominent in the somatosensory cortex and equally distributed in both
contralateral and ipsilateral hemispheres. This study shows that prolonged
stimulation of the human fingertip engages the cortex in widespread bilateral
processing of tactile information, with different modulations of the theta and
alpha bands across time.
PMID- 28497236
TI - [Atrial fibrillation].
PMID- 28497237
TI - Efficacy of long-term nonsteroidal antiinflammatory drug treatment on magnetic
resonance imaging-determined bone marrow oedema in early, active axial
spondyloarthritis patients.
AB - To assess the efficacy of long-term treatment with nonsteroidal antiinflammatory
drugs (NSAIDs) on bone marrow oedema (BMO) of the sacroiliac joint in newly
diagnosed axial spondyloarthritis (SpA) with a symptom duration of less than 4
years, a single-center, open-label study in a cohort of consecutive patients with
newly diagnosed axial SpA was conducted. Eligible patients had magnetic resonance
imaging (MRI)-determined BMO of the sacroiliac joint at baseline, had a symptom
duration of less than 4 years, and were naive to NSAIDs. After the baseline MRI,
an optimal dose of NSAID was administered for 24 or 48 weeks. BMO of sacroiliac
joint was quantified by applying the Spondyloarthritis Research Consortium of
Canada (SPARCC) system. Disease activity was expressed using the Ankylosing
Spondylitis Disease Activity Score (ASDAS). Primary end points were improvement
in BMO of sacroiliac joint at week 24 or week 48. Forty-three patients were
recruited, and 33 patients eventually completed the study, including 10 patients
having follow-up MRI at week 24 and 23 patients having follow-up MRI at week 48.
Overall, the mean of SPARCC score decreased from 21.8 +/- 16.1 at baseline to
10.2 +/- 12.8 at follow-up (p < 0.001). 75.8% of the patients displayed a
minimally important change, and 30.3% became free of BMO. The mean of ASDAS-CRP
decreased from 3.1 +/- 1.0 at baseline to 2.1 +/- 1.0 at follow-up (p < 0.001).
Long-term treatment with optimal dose NSAIDs could significantly alleviate BMO of
sacroiliac joint in early and active axial SpA.
PMID- 28497240
TI - In Vivo Anticancer Efficacy and Toxicity Studies of a Novel Polymer Conjugate N
Acetyl Glucosamine (NAG)-PEG-Doxorubicin for Targeted Cancer Therapy.
AB - A novel polymer-drug conjugate, polyethylene glycol-N-(acetyl)-glucosamine
doxorubicin (PEG-NAG-DOX) was evaluated in this study for its in vivo potential
for treatment of tumours demonstrating improved efficacy and reduced toxicity.
The proposed polymer-drug conjugate comprised of polyethylene glycol-maleimide
(mPEG-MAL, 30000 Da) as a carrier, doxorubicin (DOX) as an anticancer drug and N
acetyl glucosamine (NAG) as a targeting moiety as well as penetration enhancer.
Doxorubicin has a potent and promising anticancer activity; however, severe
cardiotoxicity limits its application in cancer treatment. By modifying DOX in
PEG-NAG-DOX prodrug conjugate, we aimed to eliminate this limitation. In vivo
anticancer efficacy of the conjugate was evaluated using BDF mice-induced skin
melanoma model by i.v. administration of DOX conjugates. Anticancer efficacy
studies were done by comparing tumour volume, body weight, organ index and
percent survival rate of the animals. Tumour suppression achieved by PEG-NAG-DOX
at the cumulative dose of 7.5 mg/kg was two-fold better than that achieved by DOX
solution. Also, the survival rate for PEG-NAG-DOX conjugate was >70% as compared
to <50% survival rate for DOX solution. In addition, toxicity studies and
histopathological studies revealed that while maintaining its cytotoxicity
towards tumour cells, PEG-NAG-DOX conjugate showed no toxicities to major organs.
Therefore, PEG-NAG-DOX conjugate can be suggested as a desirable candidate for
targeted cancer therapy.
PMID- 28497238
TI - Obesity-related mortality in France, Italy, and the United States: a comparison
using multiple cause-of-death analysis.
AB - OBJECTIVES: We investigate the reporting of obesity on death certificates in
three countries (France, Italy, and the United States) with different levels of
prevalence, and we examine which causes are frequently associated with obesity.
METHODS: We use cause-of-death data for all deaths at ages 50-89 in 2010-2011.
Since obesity may not be the underlying cause (UC) of death, we compute age- and
sex-standardized death rates considering all mentions of obesity (multiple causes
or MC). We use cluster analyses to identify patterns of cause-of-death
combinations. RESULTS: Obesity is selected as UC in no more than 20% of the
deaths with a mention of obesity. Mortality levels, whether measured from the UC
or the MC, are weakly related to levels of prevalence. Patterns of cause-of-death
combinations are similar across the countries. In addition to strong links with
cardiovascular diseases and diabetes, we identify several less familiar
associations. CONCLUSIONS: Considering all mentions on the deaths certificates
reduces the underestimation of obesity-related mortality based on the UC only. It
also enables us to describe the various mortality patterns involving obesity.
PMID- 28497239
TI - Validation of the revised International Prognostic Scoring System in patients
with myelodysplastic syndrome in Japan: results from a prospective multicenter
registry.
AB - The Japanese National Research Group on Idiopathic Bone Marrow Failure Syndromes
has been conducting prospective registration, central review, and follow-up study
for patients with aplastic anemia and myelodysplastic syndrome (MDS) since 2006.
Using this database, we retrospectively analyzed the prognosis of patients with
MDS. As of May 2016, 351 cases were registered in this database, 186 of which
were eligible for the present study. Kaplan-Meier analysis showed that overall
survival (OS) curves of the five risk categories stipulated by the revised
international prognostic scoring system (IPSS-R) were reasonably separated. 2
year OS rates for the very low-, low-, intermediate-, high-, and very high-risk
categories were 95, 89, 79, 35, and 12%, respectively. In the same categories,
incidence of leukemic transformation at 2 years was 0, 10, 8, 56, and 40%,
respectively. Multivariate analysis revealed that male sex, low platelet counts,
increased blast percentage (>2%), and high-risk karyotype abnormalities were
independent risk factors for poor OS. Based on these data, we classified Japanese
MDS patients who were classified as intermediate-risk in IPSS-R, into the lower
risk MDS category, highlighting the need for careful assessment of treatments
within low- and high-risk treatment protocols.
PMID- 28497241
TI - Fighting against evolution of antibiotic resistance by utilizing evolvable
antimicrobial drugs.
AB - Antibiotic resistance is a worldwide public health problem (Bush et al. in Nat
Rev Microbiol 9:894-896, 2011). The lack of effective therapies against resistant
bacteria globally leads to prolonged treatments, increased mortality, and
inflating health care costs (Oz et al. in Mol Biol Evol 31:2387-2401, 2014;
Martinez in Science 321:365-367, 2008; Lipsitch et al. in Proc Natl Acad Sci USA
97:1938-1943, 2000; Taubes in Science 321:356-361, 2008; Laxminarayan et al. in
Lancet, 2016; Laxminarayan et al. in Lancet Infect Dis 13:1057-1098, 2013).
Current efforts towards a solution of this problem can be boiled down to two main
strategies: (1) developing of new antimicrobial agents and (2) searching for
smart strategies that can restore or preserve the efficacy of existing
antimicrobial agents. In this short review article, we discuss the need for
evolvable antimicrobial agents, focusing on a new antimicrobial technology that
utilizes peptide-conjugated phosphorodiamidate morpholino oligomers to inhibit
the growth of pathogenic bacteria by targeting bacterial genes.
PMID- 28497242
TI - [New Sepsis-3 definition : Do we have to treat sepsis before we can diagnose it
from now on?]
AB - The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis
3) have been available since the beginning of 2016. SEPSIS-3 completely replaces
the old SIRS criteria in the definition of sepsis and defines sepsis from now on
as "life-threatening organ dysfunction caused by a dysregulated host response to
infection". However, it seems questionable whether in clinical practice the new
definition is really superior to the old one. The most important question is the
following: Is it helpful to have a definition that first recognizes a patient
once organ dysfunction has occurred and the patient already needs intensive care?
PMID- 28497243
TI - ["Kids Save Lives"-resuscitation training for schoolchildren : Systematic
review].
AB - BACKGROUND: Even in western developed countries, the probability of survival
after out-of-hospital cardiac arrest (OHCA) is only 6-10%. In order to improve
survival after OHCA, early initiation of cardiopulmonary resuscitation (CPR) by
laypersons is essential. Introduction of CPR training in schoolchildren seems to
be effective to increase lay-CPR rates. OBJECTIVE: The objective of the present
investigation was to elucidate educational aspects of teaching schoolchildren in
CPR and to summarize campaigns related to a comprehensive establishment of lay
CPR worldwide. MATERIALS AND METHODS: A literature research in PubMed was
performed, the cutoff date was 27 February 2017. Overall, 192 abstracts were
analyzed; 51 articles were considered relevant and included in the manuscript. An
additional keyword research in Google revealed >230,000 entries, and 20 of those
were included in the present manuscript. RESULTS: A minimum age of 12-13 years is
required to achieve a comparable quality of CPR to adult basic life support
(BLS). Key issues are (i) the correct detection of a cardiac arrest, (ii) a
correctly performed call for help, (iii) thoracic compressions and (iv) if
applicable, the initiation of adequate mouth-to-mouth ventilation. Practical
training showed a significantly higher CPR quality compared to theoretical
training only or to the use of instruction or online videos only. Worldwide
implementation of a 2-h BLS training per year in children from the age of 12 or
younger is recommended by the "Kids Save Lives"- statement since 2015. In
Germany, implementation at the level of the federal states has progressed to
different degrees.
PMID- 28497244
TI - Invisible Voices: An Intersectional Exploration of Quality of Life for Elderly
South Asian Immigrant Women in a Canadian Sample.
AB - Despite the emerging presence of South Asian elderly population in Canada, there
continues to be a paucity of research concerning the immigration and
acculturation experiences of these marginalized elderly populations and their
quality of life. This research builds knowledge of the quality of life
experiences faced by South Asian elderly immigrant women residing in Canada using
an intersectional analytical framework. While there is a gradually developing
body of research regarding elder persons globally, the present research is unique
in that explores challenges, stresses and strains, and builds an understanding of
the treatment of older ethnic minorities and immigrant families. Furthermore,
this research has implications for policies and practices governing these growing
aging populations. Finally, this research gives voice to a "silenced" and
invisible group of elders whose stories may help to make improvements in the
quality of living and well-being for the aging South Asian immigrant population
in Canada.
PMID- 28497245
TI - Single species growth consuming inorganic carbon with internal storage in a
poorly mixed habitat.
AB - This paper presents a PDE system modeling the growth of a single species
population consuming inorganic carbon that is stored internally in a poorly mixed
habitat. Inorganic carbon takes the forms of "CO2" (dissolved CO2 and carbonic
acid) and "CARB" (bicarbonate and carbonate ions), which are substitutable in
their effects on algal growth. We first establish a threshold type result on the
extinction/persistence of the species in terms of the sign of a principal
eigenvalue associated with a nonlinear eigenvalue problem. If the habitat is the
unstirred chemostat, we add biologically relevant assumptions on the uptake
functions and prove the uniqueness and global attractivity of the positive steady
state when the species persists.
PMID- 28497246
TI - Neural Correlates of Explicit Versus Implicit Facial Emotion Processing in ASD.
AB - The underlying neural mechanisms of implicit and explicit facial emotion
recognition (FER) were studied in children and adolescents with autism spectrum
disorder (ASD) compared to matched typically developing controls (TDC). EEG was
obtained from N = 21 ASD and N = 16 TDC. Task performance, visual (P100, N170)
and cognitive (late positive potential) event-related-potentials, as well as
coherence were compared across groups. TDC showed a task-dependent increase and a
stronger lateralization of P100 amplitude during the explicit task and task
dependent modulation of intra-hemispheric coherence in the beta band. In
contrast, the ASD group showed no task dependent modulation. Results indicate
disruptions in early visual processing and top-down attentional processes as
contributing factors to FER deficits in ASD.
PMID- 28497247
TI - [Medial closed wedge osteotomy of the distal femur in biplanar technique and a
specific plate fixator].
AB - OBJECTIVE: Correction of distal femur deformity by closed-wedge biplanar
osteotomy. INDICATIONS: Metaphyseal frontal plane deformities of the femur.
CONTRAINDICATIONS: Osteoarthritis of the contralateral compartment, total loss of
the contralateral meniscus, acute/chronic infection, limited range-of-motion,
poor soft-tissue conditions at site of surgery. SURGICAL TECHNIQUE: Skin incision
at metaphyseal area of femur. Local exposure of bone. Marking of planned
osteotomies. Incomplete posterior osteotomies, complete anterior osteotomy. Wedge
removal and closure. Radiological control of alignment. Fixation with specific
plate fixator for the medial femur (TomoFix MDF). Submuscular plate fixation.
Wound closure. POSTOPERATIVE MANAGEMENT: Elastic bandage, suction drain removal
and walking with crutches on day 1. Partial weight bearing (15 kg) for the first
4 weeks; X-ray control on day 3 and 4 weeks after surgery, walking without
crutches depending on healing of osteotomy. Thrombosis prophylaxis. RESULTS: From
January 2005 to October 2008, 60 patients were treated. Average wedge size 7.6
mm; age 39.7 years; mean follow-up 21 months; 7 revision surgeries: 3
delayed/nonunion of the osteotomy, one superficial infection, one deep infection,
one hematoma, and one fracture proximal of the internal plate fixator. Tegner
activity score pre-/postoperative 2.8 (1-4)/5.6 (2-9); VAS score pre
/postoperative 6.8 (2-9)/3.1 (0-8). From 2014-2015, 107 femur osteotomies
performed: 4 delayed healing, one plate breakage. Healing of all other
osteotomies in 4-6 weeks. No loss of range-of-motion with the muscle-sparing
surgical technique.
PMID- 28497249
TI - The honeymoon period repeatedly appears in two cases of type 1 diabetes mellitus.
PMID- 28497248
TI - [Aseptic loosening of total ankle replacement : One-stage revision ankle
arthroplasty].
AB - OBJECTIVE: To revise one or both loosened prosthesis components, to achieve
postoperative pain relief, and preserve ankle range of motion. INDICATIONS:
Aseptic loosening of the tibial and/or talar ankle prosthesis components without
substantial bone defect of the tibial or talar bone stock. CONTRAINDICATIONS:
General surgical or anesthesiological risks, infections, critical soft tissue
conditions, nonmanageable hindfoot instability, neurovascular impairment of the
lower extremity, neuroarthropathy (e. g. Charcot arthropathy), substantial
nonreconstructable osseous defects with or without cysts on the tibial and/or
talar side, non-compliance, patients with primary total ankle replacement (TAR)
using intramedullary fixation (stem fixation), patients with severely reduced
bone quality, insulin-dependent diabetes mellitus, smoking, unrealistic patient
expectations, patients with high activity in sports. SURGICAL TECHNIQUE: Exposure
of the ankle joint using the previous incision (anterior or lateral transfibular
approach). Mobilization and removal of loosened prosthesis component. Careful
debridement of bone stock at bone-prosthesis interface. Determination of
prosthesis component size. Implantation of definitive prosthesis components.
Wound closure in layers. POSTOPERATIVE MANAGEMENT: A soft wound dressing is used.
Thromboprophylaxis is recommended. Patient mobilization starts at postoperative
day 1 with 15 kg partial weight bearing using a stabilizing walking boot or cast
for 6 weeks. Following clinical and radiographic follow-up at 6 weeks, full
weight bearing is initiated gradually. RESULTS: Between January 2007 and December
2012 a one-stage revision TAR was performed in 14 patients with a mean age of
52.7 +/- 12.0 years (29.8-70.5 years). The indication for revision surgery was
aseptic loosening of one or both prosthesis components. The mean time between the
initial TAR and revision surgery was 5.9 +/- 2.9 years (2.0-11.5 years). In 2
patients a tibiotalocalcaneal arthrodesis was performed due to painful aseptic
loosening of revision TAR. In all patients a significant pain relief was
observed.
PMID- 28497250
TI - People's Understanding of Verbal Risk Descriptors in Patient Information
Leaflets: A Cross-Sectional National Survey of 18- to 65-Year-Olds in England.
AB - INTRODUCTION: Evidence suggests the current verbal risk descriptors used to
communicate side effect risk in patient information leaflets (PILs) are
overestimated. OBJECTIVES: The aim was to establish how people understand the
verbal risk descriptors recommended for use in PILs by the European Commission
(EC), and alternative verbal risk descriptors, in the context of mild and severe
side effects. METHODS: A cross-sectional online survey was carried out by a
market research company recruiting participants aged between 18 and 65 years
living in England. Data were collected between 18 March and 1 April 2016.
Participants were given a hypothetical scenario regarding the risk of mild or
severe medication side effects and asked to estimate how many out of 10,000
people would be affected for each of the verbal risk descriptors being tested.
RESULTS: A total of 1003 participants were included in the final sample. The
risks conveyed by the EC recommended verbal risk descriptors were greatly
overestimated by participants. Two distinct distributions were apparent for
participant estimates of side effect risks: those for 'high risk' verbal
descriptors (e.g. 'common', 'likely', 'high chance') and those for 'low risk'
verbal descriptors (e.g. 'uncommon', 'unlikely', 'low chance'). Within these two
groups, the distributions were near to identical regardless of what adverb (e.g.
very, high, fair) or adjective (e.g. common, likely, chance) was used. The EC
recommended verbal risk descriptors were more likely to be understood in
accordance with their intended meanings when describing severe side effects. Very
few demographic or psychological factors were consistently associated with how
well participants understood the EC recommended verbal risk descriptors.
DISCUSSION: The current verbal risk descriptors used in PILs are ineffective at
best and misleading at worst. Discontinuing the use of verbal risk descriptors
would limit the likelihood of people overestimating the risk of side effects.
PMID- 28497251
TI - Minimally Invasive Surgery for Complicated Diverticulitis.
PMID- 28497252
TI - Gallbladder Cancer Presenting with Jaundice: Uniformly Fatal or Still Potentially
Curable?
AB - BACKGROUND: Jaundice as a presenting symptom of gallbladder cancer has
traditionally been considered to be a sign of advanced disease, inoperability,
and poor outcome. However, recent studies have demonstrated that a small subset
of these patients can undergo resection with curative intent. METHODS: Patients
with gallbladder cancer managed surgically from 2000 to 2014 in 10 US academic
institutions were stratified based on the presence of jaundice at presentation
(defined as bilirubin >=4 mg/ml or requiring preoperative biliary drainage).
Perioperative morbidity, mortality, and overall survival were compared between
jaundiced and non-jaundiced patients. RESULTS: Of 400 gallbladder cancer patients
with available preoperative data, 108 (27%) presented with jaundice while 292
(73%) did not. The fraction of patients who eventually underwent curative-intent
resection was much lower in the presence of jaundice (n = 33, 30%) than not (n =
218, 75%; P < 0.001). Jaundiced patients experienced higher perioperative
morbidity (69 vs. 38%; P = 0.002), including a much higher need for reoperation
(12 vs. 1%; P = 0.003). However, 90-day mortality (6.5 vs. 3.6%; P = 0.35) was
not significantly higher. Overall survival after resection was worse in jaundiced
patients (median 14 vs. 32 months; P < 0.001). Further subgroup analysis within
the jaundiced patients revealed a more favorable survival after resection in the
presence of low CA19-9 < 50 (median 40 vs. 12 months; P = 0.003) and in the
absence of lymphovascular invasion (40 vs. 14 months; P = 0.014). CONCLUSION:
Jaundice is a powerful preoperative clinical sign of inoperability and poor
outcome among gallbladder cancer patients. However, some of these patients may
still achieve long-term survival after resection, especially when preoperative
CA19-9 levels are low and no lymphovascular invasion is noted pathologically.
PMID- 28497253
TI - Effects of juvenile hormone analogue (methoprene) and 20-hydroxyecdysone on
reproduction in Polygonia c-aureum (Lepidoptera: Nymphalidae) in relation to
adult diapause.
AB - We investigated the effects of juvenile hormone analogue (methoprene) and 20
hydroxyecdysone on female and male reproduction in a nymphalid butterfly,
Polygonia c-aureum. This butterfly has a facultative adult diapause controlled by
the corpora allata and brain. Methoprene seems to terminate reproductive
diapause, although transplantation experiments indicate that the activity of the
corpora allata does not affect male mating behavior Endo (Dev Growth Differ 15:1
10, 1973a), suggesting that the brain may be involved in diapause. We found that
exposure to methoprene promoted the development of ovaries and of the male
accessory glands and simplex. On the other hand, exposure to 20-hydroxyecdysone
did not promote the development of female and male reproductive organs and
eupyrene sperm movement from the testis to the duplex in the adult stage.
Ecdysteroid titer in both sexes was consistently low in adults. These results
suggest that imaginal diapause is largely regulated by juvenile hormone in this
butterfly.
PMID- 28497255
TI - [Acute focal neurological deficits in the emergency room].
AB - A focal neurological deficit with sudden onset or rapid progression is an
alarming symptom indicating a neurological disorder with often urgent need for
treatment. Particularly in the emergency room, where time and resources are
limited, it is necessary to rapidly assign such a focal neurological deficit to a
certain syndrome and to define a suspected diagnosis in order to execute the
correct diagnostics and emergency therapy. In this article, we highlight frequent
and typical neurological disorders presenting in the emergency room and their
corresponding focal neurological deficits. The article and a suggested algorithm
are to guide less-experienced colleagues to find quick steps from acute symptoms
to diagnosis and emergency treatment of frequent and relevant neurological
disorders in the emergency room.
PMID- 28497254
TI - 9-Phenanthrol modulates postinhibitory rebound and afterhyperpolarizing
potentials in an excitatory motor neuron of the medicinal leech.
AB - Postinhibitory rebound (PIR) responses in leech dorsal excitatory motor neurons
(cell DE-3) are eliminated by Ca2+ channel blockers but also exhibit a strong
dependence on extracellular Na+. These features could be explained by a voltage
gated Ca2+ current acting in concert with a Ca2+-activated nonspecific current
(ICAN). In vertebrates, ICAN is associated with TRPM4 channels which are blocked
selectively by 9-phenanthrol. Here, we show that 9-phenanthrol selectively
inhibits a late phase of PIR and simultaneously enhances afterhyperpolarizing
potentials (AHPs). Bath application of NNC 55-0396 or Cd2+ combined with ion
substitution experiments indicate that a low-voltage-activated Ca2+ current plays
a key role in generating PIR and that Ca2+ influx through low- or high-voltage
activated Ca2+ channels can trigger AHPs via activation of a Ca2+-dependent K+
current. We also demonstrate modulation of rebound responses by other ICAN
blockers such as gadolinium and flufenamic acid, as well as the calmodulin
antagonist W-7. We discuss how these results provide additional insights into the
specific types of ionic currents underlying rebound responses of motor neuron DE
3 in the medicinal leech.
PMID- 28497256
TI - [Pharmacotherapy of Parkinson's disease : Aspects of drug safety].
AB - BACKGROUND: This overview focuses on the aspects of the pharmacotherapy of
Parkinson's disease, which is one of the most common disorders of the nervous
system. This article presents the complexity of the pharmacotherapy of geriatric
patients with neurological diseases. OBJECTIVES: Information about the potential
risk factors and aspects of drug safety in the pharmacotherapy of Parkinson's
disease. MATERIALS AND METHODS: Selective literature search using PubMed and the
scientific-clinical experience of the authors. RESULTS: Patients with Parkinson's
disease are usually geriatric patients with concomitant diseases. As a result
they are often treated with comedication which leads to a complex medication
regime with more than five drugs. Such polypharmacy increases the risk of adverse
drug events due to the rising number of possible interactions and
contraindications. To control this risk and maintain a safe therapy, certain
measures should be considered. This implies additional need for educational work
in order to create awareness regarding potential adverse drug events. In certain
cases of diagnosed comorbidities or relevant drug prescriptions in the medication
regime, follow-up examinations should be conducted. CONCLUSION: Specific
parameters of Parkinson's disease, the health-related quality of life of affected
patients and the quality of pharmacotherapeutic drug safety can be improved by
targeted monitoring of the medication regime. As a result, the overall drug
safety can be increased.
PMID- 28497257
TI - [Therapy of migranes].
AB - In migraine attack treatment analgesics such as nonsteroidal anti-inflammatory
drugs and triptans can be utilized. The efficacy of acute attack treatment is
relevant to prevent migraine chronification. For prophylactic treatment beta
blockers, tricyclic antidepressants, flunarizine, antiepileptics and
onabotulinumtoxin A are available. There is evidence that some other substances
(e. g. sartans) are also efficacious in this regard. Furthermore, nondrug
approaches are essential in migraine therapy. Early education and prophylactic
treatment of patients at risk may prevent from medication overuse headache.
Noninvasive neuromodulatory approaches as supraorbital or vagal nerve stimulation
are emerging methods for prophylactic treatment. Ongoing clinical trials
investigate an oral calcitonin gene-related peptide (CGRP) antagonist for acute
treatment and several prophylactic monoclonal CGRP or CGRP receptor-antibodies
regarding safety, side effects and efficacy as new therapeutic options.
PMID- 28497258
TI - Clinical Pharmacokinetics and Mass Balance of Veliparib in Combination with
Temozolomide in Subjects with Nonhematologic Malignancies.
AB - BACKGROUND AND OBJECTIVES: Veliparib is an orally active potent poly(ADP-ribose)
polymerase (PARP) inhibitor currently in phase III clinical trials in solid
tumors. This phase I study evaluated the pharmacokinetics and mass balance of
veliparib administered alone and in combination with temozolomide, and assessed
any potential pharmacokinetic drug-drug interaction between veliparib and
temozolomide. METHODS: This was an open-label, dose-escalation study of veliparib
in combination with temozolomide in 42 subjects with nonhematologic malignancies.
Veliparib was administered orally at doses ranging from 10 to 80 mg twice daily
on days 1-7, and temozolomide was administered orally at 150-200 mg/m2 once daily
on days 1-5 of each 28-day cycle. The pharmacokinetics of veliparib, its M8
metabolite, and temozolomide, as well as urinary excretion of unchanged veliparib
and its M8 metabolite, were determined. RESULTS: Mean veliparib maximum observed
plasma concentration (C max) and area under the plasma concentration-time curve
for the first 6 h postdose (AUC6) values increased dose proportionally in the
veliparib 10-80 mg twice-daily dose range. The urinary recovery of veliparib dose
as the unchanged parent compound alone and together with the M8 metabolite was 73
+/- 18 and 90 +/- 22%, respectively, over a 12-h dosing interval on day 6 of
Cycle 1. Veliparib and temozolomide pharmacokinetic exposures were not affected
when administered together. CONCLUSIONS: Veliparib is a Biopharmaceutical
Classification System (BCS) Class 1 compound, with no less than 90% of the dose
absorbed and an oral bioavailability of at least 73%. Veliparib is primarily
eliminated by renal excretion. Veliparib exhibited linear pharmacokinetics in the
10-80 mg twice-daily dose range. No pharmacokinetic interaction was observed when
veliparib and temozolomide were administered together. CLINICAL TRIAL
REGISTRATION NUMBER: NCT00526617.
PMID- 28497259
TI - Safety and Tolerability of Intravenous Valproic Acid in Healthy Subjects: A Phase
I Dose-Escalation Trial.
AB - BACKGROUND: Valproic acid, a histone deacetylase inhibitor, has beneficial
effects in the setting of cancer, neurologic diseases, and traumatic injuries. In
animal models of traumatic injury, a single dose of valproic acid has been shown
to reduce mortality. The purpose of this trial was to determine the maximum
tolerated single dose of intravenous valproic acid in healthy humans. METHODS: A
double-blinded, placebo-controlled, dose-escalation trial design was used to
identify dose-limiting toxicities in healthy subjects who received a single dose
of intravenous valproic acid. Patients were monitored for adverse events and data
were collected for pharmacokinetic, pharmacodynamic, and safety profiling of
valproic acid. RESULTS: Fifty-nine healthy subjects (mean 30 +/- 12 years) were
enrolled. Forty-four subjects received valproic acid in doses from 15 to 150
mg/kg. The most common adverse events were hypoacusis (n = 19), chills (n = 18),
and headache (n = 16). The maximum tolerated dose was 140 mg/kg. Dose-limiting
toxicities included headache and nausea lasting longer than 12 h. No drug-related
abnormalities were seen in other safety measures including laboratory tests,
hemodynamic parameters, cardiac rhythm monitoring, and cognitive testing. A two
compartment model was predictive of valproic acid concentration-time profiles,
with a strong correlation (R 2 = 0.56) observed between the number of reported
adverse events and the dose level. CONCLUSIONS: The maximum tolerated dose of
intravenous valproic acid in healthy subjects is 140 mg/kg. This is significantly
higher than the previously established maximum tolerated dose of 60-75 mg/kg.
Next, the safety and tolerability of high-dose valproic acid will be tested in
trauma patients in hemorrhagic shock. ClinicalTrials.gov Identifier: NCT01951560.
PMID- 28497261
TI - Othmar Schubiger.
PMID- 28497260
TI - A Physiologically Based Pharmacokinetic Perspective on the Clinical Utility of
Albumin-Based Dose Adjustments in Critically Ill Patients.
AB - INTRODUCTION: In hypo-albuminemia, the extent of albumin binding of a drug
decreases. The resulting change in plasma protein binding only rarely leads to
clinically relevant changes in unbound drug exposure. Nevertheless, in the
critically ill, a tendency to increase dosing of anti-infective therapy is seen
in patients experiencing hypo-albuminemia. To reconcile basic pharmacological
principles with current clinical practice, this work presents a pharmacologically
based pharmacokinetic simulation study to emphasize the (lack of) effect of
altered plasma protein binding on a drug's concentration-time profile and
associated pharmacokinetic parameters. METHODS: Four virtual compounds,
representing a broad chemical space (low/high clearance/volume of distribution),
were created and administered to a virtual population of normal patients and
three types of hypo-albuminemic patients in Simcyp(r). The influence of decreased
plasma protein binding in hypoalbuminemia on the pharmacokinetic parameters and
profiles of these four compounds was investigated. RESULTS: Simulation results
showed that while high-clearance compounds suffer from increased unbound exposure
with decreased plasma protein binding, the unbound exposure of low-clearance
compounds was unaffected. However, for the subset of low-clearance compounds with
a small volume of distribution, it appeared that there were still alterations in
their plasma concentration-time profiles. Since this may lead to different times
above a minimum inhibitory concentration value, this might affect the bacterial
killing for some anti-infective drugs. Overall, for any compound involved in the
simulations, the unbound exposure did not decrease in plasma protein binding
subjects relative to normal plasma protein binding subjects. DISCUSSION: This
finding is in line with the few case-controlled studies in the literature. Hence,
increasing the dose/dosing frequency seems futile and might reduce the benefit
risk ratio for narrow therapeutic index drugs. Moreover, these simulations
indicate that when only total plasma concentrations and derived pharmacokinetic
parameters are considered, incorrect conclusions will be drawn.
PMID- 28497262
TI - Arterial tortuosity in patients with spontaneous cervical artery dissection.
AB - PURPOSE: The aim of this study was to test the hypothesis that patients with
spontaneous cervical artery dissection (CeAD) have increased arterial tortuosity,
and the objective quantification of such a tortuosity may aid in the
identification of subjects at increased risk of disease. METHODS: In the setting
of a hospital-based, case-control study, we used the vertebral tortuosity index
(VTI) measured on magnetic resonance angiography, a validated method for the
assessment and quantification of arterial tortuosity, to compare the degree of
tortuosity in a series of consecutive patients with spontaneous CeAD and of age-
and sex-matched patients with ischemic stroke unrelated to CeAD (non-CeAD IS) and
stroke-free subjects. RESULTS: The study group was composed of 102 patients with
CeAD (mean age, 44.5 +/- 7.8 years; 66.7% men), 102 with non-CEAD IS, and 102
stroke-free subjects. The VTI was higher in the group of patients with CeAD
(median, 7.3; 25th-75th percentile, 10.2) compared with that of non-CeAD IS
(median, 3.4; 25th-75th percentile, 4.4) and of stroke-free subjects (median,
4.0; 25th-75th percentile, 2.9; p <= 0.001), and was independently associated to
the risk of CeAD (OR, 1.18; 95% CI, 1.09-1.29) in multivariable regression
analysis. The degree of tortuosity also tended to be higher in CeAD patients who
experienced short-term recurrence (5.8%; median, 20.2; 25th-75th percentile,
31.2) than in those without recurrent events (median, 7.2; 25th-75th percentile,
9.4; p = 0.074). CONCLUSION: CeAD patients exhibit increased arterial tortuosity.
This might have potential implications for better understanding of the
pathophysiology of the disease as well as clinical utility in evaluation,
prognostication, and decision-making of affected individuals.
PMID- 28497263
TI - Radiologic head CT interpretation errors in pediatric abusive and non-abusive
head trauma patients.
AB - BACKGROUND: Pediatric head trauma, including abusive head trauma, is a
significant cause of morbidity and mortality. OBJECTIVE: The purpose of this
research was to identify and evaluate radiologic interpretation errors of head
CTs performed on abusive and non-abusive pediatric head trauma patients from a
community setting referred for a secondary interpretation at a tertiary pediatric
hospital. MATERIALS AND METHODS: A retrospective search identified 184 patients
<5 years of age with head CT for known or potential head trauma who had a primary
interpretation performed at a referring community hospital by a board-certified
radiologist. Two board-certified fellowship-trained neuroradiologists at an
academic pediatric hospital independently interpreted the head CTs, compared
their interpretations to determine inter-reader discrepancy rates, and resolved
discrepancies to establish a consensus second interpretation. The primary
interpretation was compared to the consensus second interpretation using the
RADPEERTM scoring system to determine the primary interpretation-second
interpretation overall and major discrepancy rates. MRI and/or surgical findings
were used to validate the primary interpretation or second interpretation when
possible. The diagnosis of abusive head trauma was made using clinical and
imaging data by a child abuse specialist to separate patients into abusive head
trauma and non-abusive head trauma groups. Discrepancy rates were compared for
both groups. Lastly, primary interpretations and second interpretations were
evaluated for discussion of imaging findings concerning for abusive head trauma.
RESULTS: There were statistically significant differences between primary
interpretation-second interpretation versus inter-reader overall and major
discrepancy rates (28% vs. 6%, P=0.0001; 16% vs. 1%, P=0.0001). There were
significant differences in the primary interpretation-second interpretation
overall and major discrepancy rates for abusive head trauma patients compared to
non-abusive head trauma patients (41% vs 23%, P=0.02; 26% vs. 12%, P=0.03). The
most common findings resulting in major radiologic interpretation errors were
fractures and subdural hemorrhage. Differences in the age of the patient and the
percentage of patients with hemorrhage were statistically significant between the
abusive head trauma versus non-abusive head trauma groups, while no statistical
difference was identified for skull fractures, ischemia, head CT radiation dose,
or presence of multiplanar or 3-D reformatted images. The second interpretation
more frequently indicated potential for abusive head trauma compared to the
primary interpretation (P=0.0001). MRI and/or surgical findings were in agreement
with the second interpretation in 29/29 (100%) of patients with discrepancies.
CONCLUSION: A high incidence of radiologic interpretation errors may occur in
pediatric trauma patients at risk for abusive head trauma who are referred from a
community hospital. This suggests value for second interpretations of head CTs at
a tertiary pediatric hospital for this patient population.
PMID- 28497264
TI - Classification of parotidectomy: a proposed modification to the European Salivary
Gland Society classification system.
AB - Parotidectomy remains the mainstay of treatment for both benign and malignant
lesions of the parotid gland. There exists a wide range of possible surgical
options in parotidectomy in terms of extent of parotid tissue removed. There is
increasing need for uniformity of terminology resulting from growing interest in
modifications of the conventional parotidectomy. It is, therefore, of paramount
importance for a standardized classification system in describing extent of
parotidectomy. Recently, the European Salivary Gland Society (ESGS) proposed a
novel classification system for parotidectomy. The aim of this study is to
evaluate this system. A classification system proposed by the ESGS was critically
re-evaluated and modified to increase its accuracy and its acceptability.
Modifications mainly focused on subdividing Levels I and II into IA, IB, IIA, and
IIB. From June 2006 to June 2016, 126 patients underwent 130 parotidectomies at
our hospital. The classification system was tested in that cohort of patient.
While the ESGS classification system is comprehensive, it does not cover all
possibilities. The addition of Sublevels IA, IB, IIA, and IIB may help to address
some of the clinical situations seen and is clinically relevant. We aim to test
the modified classification system for partial parotidectomy to address some of
the challenges mentioned.
PMID- 28497265
TI - Proteomics analysis of pleomorphic adenoma of the human parotid gland.
AB - : The objective of this study is to perform proteomic analysis of pleomorphic
adenoma (PA) in the human parotid gland (PG) with comparison of normal PG. This
is an individual prospective randomized controlled trial. This study was
performed in a tertiary referral center. Tissue samples of PG and PA were taken
after surgical excision of PG from 13 patients. Protein extracts were prepared
and protein pools created from the soluble extracts were subjected to 2D-DIGE
analysis. Proteins displaying regulation in their abundance were determined and
identified using MALDIT-OF/TOF analysis. The identified proteins were subjected
to STRING analysis for classification of the proteins based on their biological
roles in metabolic pathways. Fifteen proteins, carbonic anhydrase 1, carbonic
anhydrase 2, fibrinogen beta chain, alpha-amylase 1, heats hock protein hsp 90
alpha, clusterin, 78 kDa glucose-regulated protein, endoplasmin, alpha-amylase
2b, ATP synthase subunit alpha (mitochondrial), elongation factor 1-gamma, malate
dehydrogenase, cytoplasmic, triosephosphate isomerase, receptor of activated
protein c kinase 1, and aconitate hydratase, mitochondrial were down-regulated,
whereas 11 proteins including ig kappa chain c region, serotransferrin, vimentin,
annexin a5, glial fibrillary acidic protein, calreticulin, cartilage oligomeric
matrix protein, microfibril-associated glycoprotein 4, 14-3-3 protein epsilon,
fibulin-5, and f-box only protein 2 were up-regulated in PA samples in comparison
to healthy parotid tissue. This study described the differences observed in
protein expression patterns of the PA and normal PG. The results may provide new
insights into the pathogenesis and diagnosis of PA in human PG. LEVEL OF
EVIDENCE: 1b.
PMID- 28497266
TI - An insecticidal toxin from Nephila clavata spider venom.
AB - Spiders are the most successful insect predators given that they use their venom
containing insecticidal peptides as biochemical weapons for preying. Due to the
high specificity and potency of peptidic toxins, discoveries of insecticidal
toxins from spider venom have provided an opportunity to obtain natural compounds
for agricultural applications without affecting human health. In this study, a
novel insecticidal toxin (MU-NPTX-Nc1a) was identified and characterized from the
venom of Nephila clavata. Its primary sequence is
GCNPDCTGIQCGWPRCPGGQNPVMDKCVSCCPFCPPKSAQG which was determined by automated Edman
degradation, cDNA cloning, and MS/MS analysis. BLAST search indicated that Nc1a
shows no similarity with known peptides or proteins, indicating that Nc1a belongs
to a novel family of insecticidal peptide. Nc1a displayed inhibitory effects on
NaV and KV channels in cockroach dorsal unpaired median neurons. The median
lethal dose (LD50) of Nc1a on cockroach was 573 ng/g. Herein, a study that
identifies a novel insecticidal toxin, which can be a potential candidate and/or
template for the development of bioinsecticides, is presented.
PMID- 28497267
TI - Understanding blood gas analysis.
PMID- 28497268
TI - Pulmonary embolism following severe traumatic brain injury: incidence, risk
factors and impact outcome.
PMID- 28497269
TI - On the verge of using an immune toolbox in the intensive care unit?
PMID- 28497270
TI - The dynamic arterial elastance: a call for a cautious interpretation : Discussion
on "Predicting vasopressor needs using dynamic parameters".
PMID- 28497271
TI - Super-refractory status epilepticus: epidemiology, early predictors, and
outcomes.
PMID- 28497272
TI - Selective decontamination of the digestive tract halves the prevalence of
ventilator-associated pneumonia compared to selective oral decontamination.
PMID- 28497273
TI - CCCS-SSAI WikiRecs clinical practice guideline: vasopressor blood pressure
targets in critically ill adults with hypotension and vasopressor use in early
traumatic shock.
PMID- 28497274
TI - Endocytic receptor LRP2/megalin-of holoprosencephaly and renal Fanconi syndrome.
AB - Megalin (or LRP2) is an endocytic receptor that plays a central role in embryonic
development and adult tissue homeostasis. Loss of this receptor in congenital or
acquired diseases results in multiple organ dysfunctions, including forebrain
malformation (holoprosencephaly) and renal reabsorption defects (renal Fanconi
syndrome). Here, we describe current concepts of the mode of receptor action that
include co-receptors and a repertoire of different ligands, and we discuss how
these interactions govern functional integrity of the kidney and the brain, and
cause disease when defective.
PMID- 28497275
TI - Na +/Ca2+ exchangers and Orai channels jointly refill endoplasmic reticulum (ER)
Ca2+ via ER nanojunctions in vascular endothelial cells.
AB - We investigated the role of Na+/ Ca2+ exchange (NCX) in the refilling of
endoplasmic reticulum (ER) Ca2+ in vascular endothelial cells under various
conditions of cell stimulation and plasma membrane (PM) polarization. Better
understanding of the mechanisms behind basic ER Ca2+ content regulation is
important, since current hypotheses on the possible ultimate causes of ER stress
point to deterioration of the Ca2+ transport mechanism to/from ER itself. We
measured [Ca2+]i temporal changes by Fura-2 fluorescence under experimental
protocols that inhibit a host of transporters (NCX, Orai, non-selective transient
receptor potential canonical (TRPC) channels, sarco/endoplasmic reticulum Ca2+
ATPase (SERCA), Na+/ K+ ATPase (NKA)) involved in the Ca2+ communication between
the extracellular space and the ER. Following histamine-stimulated ER Ca2+
release, blockade of NCX Ca2+-influx mode (by 10 MUM KB-R7943) diminished the ER
refilling capacity by about 40%, while in Orai1 dominant negative-transfected
cells NCX blockade attenuated ER refilling by about 60%. Conversely, inhibiting
the ouabain sensitive NKA (10 nM ouabain), which may be localized in PM-ER
junctions, increased the ER Ca2+ releasable fraction by about 20%, thereby
supporting the hypothesis that this process of privileged ER refilling is
junction-mediated. Junctions were observed in the cell ultrastructure and their
main parameters of membrane separation and linear extension were (9.6 +/- 3.8) nm
and (128 +/- 63) nm, respectively. Our findings point to a process of privileged
refilling of the ER, in which NCX and store-operated Ca2+ entry via the stromal
interaction molecule (STIM)-Orai system are the sole protagonists. These results
shed light on the molecular machinery involved in the function of a previously
hypothesized subplasmalemmal Ca2+ control unit during ER refilling with
extracellular Ca2+.
PMID- 28497276
TI - Thermal perception thresholds among workers in a cold climate.
AB - PURPOSE: To investigate whether exposure to cold could influence the thermal
perception thresholds in a working population. METHODS: This cross-sectional
study was comprised of 251 males and females and was carried out at two mines in
the northern part of Norway and Sweden. The testing included a baseline
questionnaire, a clinical examination and measurements of thermal perception
thresholds, on both hands, the index (Digit 2) and little (Digit 5) fingers, for
heat and cold. RESULTS: The thermal perception thresholds were affected by age,
gender and test site. The thresholds were impaired by experiences of frostbite in
the fingers and the use of medication that potentially could affect neurosensory
functions. No differences were found between the calculated normative values for
these workers and those in other comparative investigations conducted in warmer
climates. CONCLUSIONS: The study provided no support for the hypothesis that
living and working in cold climate will lead to impaired thermal perception
thresholds. Exposure to cold that had caused localized damage in the form of
frostbite was shown to lead to impaired thermal perception.
PMID- 28497277
TI - Brazilin Ameliorates Diabetic Nephropathy and Inflammation in db/db Mice.
AB - Hyperglycemia and inflammation play important roles in the pathogenesis of
diabetic nephropathy (DN). Brazilin might be an effective pharmacological agent
against hyperglycemia and inflammation. In our present study, we explored whether
brazilin mitigated pathological progression, inflammation, and extracellular
matrix (ECM) accumulation in a mouse model of diabetic nephropathy. Brazilin
reduced aggravated biochemical indices of DN (proteinuria and the serum glucose
level) and renal hypertrophy. Brazilin also improved renal morphology and
inhibited macrophage infiltration, as manifested by different pathological
staining methods. Brazilin reduced the levels of pro-inflammatory cytokines and
CD68, a macrophage marker, in the kidney cortex, as revealed by both RT-PCR and
western blotting experiments. Furthermore, brazilin significantly downregulated
the serum levels of pro-inflammatory cytokines and chemokines. Interestingly,
brazilin significantly upregulated the levels of the anti-inflammatory factor IL
10, and prevented ECM accumulation. Brazilin reduced nuclear translocation of the
NF-kappaB p65 subunit both in vitro and in vivo. Thus, brazilin might be a useful
treatment for DN, through mitigating hypoglycemia, inflammation, and ECM
accumulation.
PMID- 28497278
TI - IL-35 Pretreatment Alleviates Lipopolysaccharide-Induced Acute Kidney Injury in
Mice by Inhibiting NF-kappaB Activation.
AB - Septic acute kidney injury (AKI) is a public health problem with high mortality.
Suppression of over-active inflammation is considered as a promising strategy for
septic AKI. In this study, we evaluated the prophylactic effect of interleukin
(IL)-35, the unique immune-suppressive member of IL-12 cytokine family, on
lipopolysaccharide (LPS)-induced AKI in mice, and found that compared with
control mice given empty vector, mice pretreated with plasmid encoding IL-35 (pIL
35) significantly improved renal function indicated by reduced blood urea
nitrogen (BUN) and serum creatinine (SCr), and obviously alleviated renal
pathological changes. To explore the underlying protective mechanisms, we found
that pIL-35 treatment could robustly reduce the production of renal pro
inflammatory cytokines (TNF-alpha, IL-6, and IL-1beta), with no significant
impact on IL-10, an anti-inflammatory cytokine. Furthermore, our results revealed
that IL-35 pretreatment could potentially inhibit the activation of renal NF
kappaB signaling pathway in LPS-induced AKI mice. Taken together, our study
indicated that IL-35 pretreatment could efficiently prevent LPS-induced AKI via
inhibiting NF-kappaB activation and reducing pro-inflammatory cytokine
production, and it might represent a novel therapeutic strategy against septic
AKI and other inflammatory renal diseases.
PMID- 28497279
TI - Aspiring to have the looks of a celebrity: young girls' engagement in appearance
management behaviors.
AB - : Research suggests that sexualizing media messages are present in teen media and
negatively affect young girls' body image. Yet, it is unknown whether exposure to
teen television programs is associated with girls' engagement in appearance
management behaviors. Two-wave longitudinal data among 785 girls (Mage = 11.65
years) were collected. Results show that teen television exposure was
longitudinally related to appearance management, while the reverse relation was
not supported. Approximately half of the girls indicated to manage their
appearance to some extent, and 13- to 14-year-old girls were more likely to
invest in their appearance than younger girls. Thirty percent of those who did
not manage their appearance at the start of the study indicated to have initiated
appearance management 6 months later. Frequent viewers were four times, three
times, and twice as more likely to style their hair, wear heels, and apply make
up compared to non-viewers. CONCLUSION: The current study showed that teen media
exposure plays a role in young girls' appearance management. The findings point
to a need to teach young girls about stereotypical messages in media content
directed towards them. Prevention efforts should focus on girls who frequently
watch teen media. What is Known: * Sexualizing media messages are present in teen
media. * Gender identity development is one of the key tasks during adolescence.
What is New: * Tween television exposure predicts 9- to 14-year-old girls'
engagement in appearance management over time. * Engagement in appearance
management behaviors did not predict 9- to 14-year-old girls' exposure to tween
television programs.
PMID- 28497280
TI - A minimal soft tissue damage approach of spondylolysis repair in athletes:
preliminary report.
AB - PURPOSE AND HYPOTHESIS: Both spondylolysis and spondylolisthesis come in second
place in the causes of pain among athletes. Treatment options include both
conservative management and different operative methods. Athletes and adolescents
are groups where the priority is to protect tissues from perioperative damage.
OBJECTIVE: We present our modification of the Buck's, direct pars repair method,
which we believe offers maximum protection of tissues. We used the modified
surgical method in young, competitive athletes, in whom non-surgical treatment
was not effective. METHOD: Eight pars defects in five patients were treated using
suggested method. All of them were young males (aged between 13 and 18 years),
who practice soccer professionally. We use modified method of direct repair pars
through the cannulated screw fixation, first proposed by Buck. Preoperative
preparation consists of proper analysis of computer tomography images in
multiplanar reconstruction mode: measuring screw length, measurement of
inclination angle of the optimal screw trajectory in the frontal and sagittal
plane. During the operation, the wire proper direction is performed by usage of
the predetermined angles. Starting point for guide wire was also changed to the
lower end of the facet. The fusion takes place with a screw of 3 mm diameter.
After the operation patient need to use thoracolumbar spinal orthosis as a
primary immobilization for 6 weeks and appropriate rehabilitation for another 6
weeks. We used these methods in eight pars fixations. RESULTS: All of the
patients were painless in first week after surgery. All of them underwent total
rehabilitation programme and returned to sport. CONCLUSIONS: Direct pars repair
using Buck's method with proposed modification, including adequate radiographic
preparation, the use of a thin cannulated screw and changing the point of screw
entry, allows precise and safe screw placement, regardless of the size of the
bone at the defect site.
PMID- 28497281
TI - Preoperative chest radiographs in hip fracture patients: is there any additional
value?
AB - PURPOSE: Preoperative screening in hip fracture patients is vital to minimize
perioperative complications. Preoperative chest radiographs (POCR) are performed
in many hip fracture patients. Earlier research showed that few POCR
abnormalities influence perioperative policy. However, no studies in nonelective
patient with a specific surgical conditions have been performed. With many hip
fractures per year worldwide, a significant cost reduction could be made by
performing selective POCR without compromising the quality of care. This study
assessed the need for POCR in hip fracture patients. METHOD: Retrospective
analysis of low-energy trauma patients was performed aged 18 years and older in
the VU University Medical Center for a hip fracture in a 5-year period. All
preoperative diagnostics were analyzed. All adjourned operations were evaluated.
RESULTS: A total of 642 patients were included, 70% female, matching current
epidemiologic figures. The POCR showed abnormalities in 22.6%. In 0.6% the POCR
lead to an adjournment of the operation (2.8% of abnormal POCR's). These patients
suffered from pneumonia. The POCR in these cases acted as a confirmation of the
clinical diagnosis. CONCLUSION: Many factors involving the treatment of hip
fracture patients are of importance in minimizing the risk of complications and
mortality during and after admission. In 0.6% of all performed POCR's an
abnormality leads to the adjournment of the operation. In all four cases the POCR
matched the clinical findings. Because the additional value of the POCR in hip
fracture patients was limited, we think that its selective use in clinical
abnormalities is safe and will reduce unnecessary costs.
PMID- 28497282
TI - Highly complex substrates lead to dynamic bacterial community for
polyhydroxyalkanoates production.
AB - Mixed microbial cultures (MMC) and waste/surplus substrates, as hardwood spent
sulfite liquor, are being used to decrease polyhydroxyalkanoates' (PHA)
production costs. The process involves two or three steps, being the selection
step a crucial one. For the industrial implementation of this strategy, reactor
stability in terms of both performance and microbial community presence has to be
considered. A long-term operation of a sequencing batch reactor under
feast/famine conditions was performed along with microbial community
identification/quantification using FISH and DGGE. The community was found to be
extremely dynamic, dominated by Alphaproteobacteria, with Paracoccus and
Rhodobacter present, both PHA-storing microorganisms. 16S rRNA gene clone library
further revealed that side populations' non-PHA accumulators were able to strive
(Agrobacterium, Flavobacteria, and Brachymonas). Nevertheless, reactor
performance in terms of PHA storage was stable during operation time. The
monitoring of the MMC population evolution provided information on the relation
between community structure and process operation.
PMID- 28497283
TI - The Impact of Resistance Training on Swimming Performance: A Systematic Review.
AB - BACKGROUND: The majority of propulsive forces in swimming are produced from the
upper body, with strong correlations between upper body strength and sprint
performance. There are significant gaps in the literature relating to the impact
of resistance training on swimming performance, specifically the transfer to
swimming performance. OBJECTIVE: The aims of this systematic literature review
are to (1) explore the transfer of resistance-training modalities to swimming
performance, and (2) examine the effects of resistance training on technical
aspects of swimming. METHODS: Four online databases were searched with the
following inclusion criteria: (1) journal articles with outcome measures related
to swimming performance, and (2) competitive swimmers participating in a
structured resistance-training programme. Exclusion criteria were (1)
participants with a mean age <16 years; (2) untrained, novice, masters and
paraplegic swimmers; (3) triathletes and waterpolo players; (4) swimmers with
injuries or illness; and (5) studies of starts and turns specifically. Data were
extracted using the Preferred Reporting Items for Systematic Reviews and Meta
Analyses (PRISMA) guidelines, and the Physiotherapy Evidence Database (PEDro)
scale was applied. RESULTS: For optimal transfer, specific, low-volume, high
velocity/force resistance-training programmes are optimal. Stroke length is best
achieved through resistance training with low repetitions at a high
velocity/force. Resisted swims are the most appropriate training modality for
improving stroke rate. CONCLUSION: Future research is needed with respect to the
effects of long-term resistance-training interventions on both technical
parameters of swimming and overall swimming performance. The results of such work
will be highly informative for the scientific community, coaches and athletes.
PMID- 28497284
TI - Exercise Interventions for the Prevention and Treatment of Groin Pain and Injury
in Athletes: A Critical and Systematic Review.
AB - BACKGROUND: Groin injury is a common musculoskeletal complaint for athletes
competing in a variety of sports. The extent to which exercise interventions
incorporating external load are an appropriate option for the treatment and
prevention of groin injury in athletes is not yet clear. OBJECTIVES: The aim of
this review was to describe and evaluate exercise therapy interventions and
outcomes for the treatment and prevention of groin injury with specific attention
to application of external load. DATA SOURCES: The databases Medline, PubMed,
SPORTDiscus, Web of Science, and Cochrane were searched on 18 April 2016. STUDY
ELIGIBILITY CRITERIA: This review was registered as PROSPERO CRD42016037752 and a
systematic search was conducted with the following inclusion criteria: any study
design evaluating exercise interventions for the prevention or treatment of groin
pain in athletes. DATA ANALYSIS: Two independent authors screened search results,
performed data extraction, assessed risk of bias using the modified Downs and
Black appraisal tool and determined strength and level of evidence. Reporting
standards for exercise interventions were assessed using the Consensus for
Exercise Reporting Template (CERT). RESULTS: A total of 1320 titles were
identified with 14 studies satisfying the inclusion criteria, four (29%) of which
demonstrated low risk of bias. Ten (71%) studies utilised external load as a
component of the exercise intervention. Reporting standards for exercise
intervention scores ranged from 0 to 63%. CONCLUSION: There is limited evidence
from level 2 and 3 studies indicating exercise therapy may reduce the incidence
and hazard risk of sustaining a groin injury in athletes. There is strong
evidence from level 4 studies indicating exercise therapy is beneficial as a
treatment for groin injury in athletes in terms of symptom remission, return to
sport and recurrence outcomes. However, there are limited studies with low risk
of bias, and exercise interventions for the treatment of groin injury are poorly
described.
PMID- 28497285
TI - Comparison of Periodized and Non-Periodized Resistance Training on Maximal
Strength: A Meta-Analysis.
AB - BACKGROUND: Periodization is a logical method of organizing training into
sequential phases and cyclical time periods in order to increase the potential
for achieving specific performance goals while minimizing the potential for
overtraining. Periodized resistance training plans are proposed to be superior to
non-periodized training plans for enhancing maximal strength. OBJECTIVE: The
primary aim of this study was to examine the previous literature comparing
periodized resistance training plans to non-periodized resistance training plans
and determine a quantitative estimate of effect on maximal strength. METHODS: All
studies included in the meta-analysis met the following inclusion criteria: (1)
peer-reviewed publication; (2) published in English; (3) comparison of a
periodized resistance training group to a non-periodized resistance training
group; (4) maximal strength measured by 1-repetition maximum (1RM) squat, bench
press, or leg press. Data were extracted and independently coded by two authors.
Random-effects models were used to aggregate a mean effect size (ES), 95%
confidence intervals (CIs) and potential moderators. RESULTS: The cumulative
results of 81 effects gathered from 18 studies published between 1988 and 2015
indicated that the magnitude of improvement in 1RM following periodized
resistance training was greater than non-periodized resistance training (ES =
0.43, 95% CI 0.27-0.58; P < 0.001). Periodization model (beta = 0.51; P =
0.0010), training status (beta = -0.59; P = 0.0305), study length (beta = 0.03; P
= 0.0067), and training frequency (beta = 0.46; P = 0.0123) were associated with
a change in 1RM. These results indicate that undulating programs were more
favorable for strength gains. Improvements in 1RM were greater among untrained
participants. Additionally, higher training frequency and longer study length
were associated with larger improvements in 1RM. CONCLUSION: These results
suggest that periodized resistance training plans have a moderate effect on 1RM
compared to non-periodized training plans. Variation in training stimuli appears
to be vital for increasing maximal strength, and longer periods of higher
training frequency may be preferred.
PMID- 28497286
TI - The Influence of Drinking Fluid on Endurance Cycling Performance: A Meta
Analysis.
AB - BACKGROUND: Fluid replacement during cycling exercise evolves on a spectrum from
simply drinking to thirst to planned structured intake, with both being
appropriate recommendations. However, with mixed findings suggesting fluid intake
may or may not improve endurance cycling performance (ECP) in a diverse range of
trained individuals, there is a clear need for summarised evidence regarding the
effect of fluid consumption on ECP. OBJECTIVES: (1) Determine the magnitude of
the effect of drinking fluid on performance during cycling exercise tasks of
various durations, compared with no drinking; (2) examine the relationship
between rates of fluid intake and ECP; and (3) establish fluid intake
recommendations based on the observations between rates of fluid intake and ECP.
STUDY DESIGN: Meta-analysis. METHODS: Studies were located via database searches
and cross-referencing. Performance outcomes were converted to a similar metric to
represent percentage change in power output. Fixed- and random-effects weighted
mean effect summaries and meta-regression analyses were used to identify the
impact of drinking fluid on ECP. RESULTS: A limited number of research
manuscripts (n = 9) met the inclusion criteria, producing 15 effect estimates.
Meta-regression analyses demonstrated that the impact of drinking on ECP under 20
33 degrees C ambient temperatures was duration-dependent. Fluid consumption of,
on average, 0.29 mL/kg body mass/min impaired 1 h high-intensity (80% peak oxygen
uptake [[Formula: see text]o2peak]) ECP by -2.5 +/- 0.8% (95% confidence interval
[CI] -4.1 to -0.9%) compared with no fluid ingestion. In contrast, during >1 to
<=2 h and >2 h moderate-intensity (60-70% [Formula: see text]o2peak) cycling
exercise, ECP improved by 2.1 +/- 1.5% (95% CI 1.2-2.9%) and 3.2 +/- 1.2% (95% CI
0.8-5.6%), respectively, with fluid ingestion compared with no fluid intake. The
associated performance benefits were observed when the rates of fluid intake were
in the range of 0.15-0.20 mL/kg body mass/min for >1 to <=2 h cycling exercise
and ad libitum or 0.14-0.27 mL/kg body mass/min for cycling exercise >2 h.
CONCLUSIONS: A rate of fluid consumption of between 0.15 and 0.34 mL/kg body
mass/min during high-intensity 1 h cycling exercise is associated with reductions
in ECP. When cycling at moderate intensity for >1 to <=2 h, cyclists should
expect a gain in performance of at least 2% if fluid is consumed at a rate of
0.15-0.20 mL/kg body mass/min. For cycling exercise >2 h conducted at moderate
intensity, consuming fluid ad libitum or at a rate of 0.14-0.27 mL/kg body
mass/min should improve performance by at least 3%. Until further research is
conducted, these recommendations should be used as a guide to inform hydration
practices.
PMID- 28497287
TI - Role of nitrite in the competition between denitrification and DNRA in a
chemostat enrichment culture.
AB - Denitrification and dissimilatory nitrate reduction to ammonium (DNRA) are two
microbial processes that compete for oxidized nitrogen compounds in the
environment. The objective of this work was to determine the role of nitrite
versus nitrate as terminal electron acceptor on the competition between DNRA and
denitrification. Initially, a mixed culture chemostat was operated under nitrate
limitation and performed DNRA. Stepwise, the influent nitrate was replaced with
nitrite until nitrite was the sole electron acceptor and N-source present.
Despite changing the electron acceptor from nitrate to nitrite, the dominant
process remained DNRA and the same dominant organism closely related to Geobacter
lovleyi was identified. Contrary to previous studies conducted with a complex
substrate in marine microbial communities, the conclusion of this work is that
nitrate versus nitrite as electron acceptor does not generally control the
competition between DNRA and denitrification. Our results show that the effect of
this ratio must be interpreted in combination with other environmental factors,
such as the type and complexity of the electron donor, pH, or sulfide
concentrations.
PMID- 28497288
TI - Novel signal peptides improve the secretion of recombinant Staphylococcus aureus
Alpha toxinH35L in Escherichia coli.
AB - Secretion of heterologous proteins into Escherichia coli cell culture medium
offers significant advantages for downstream processing over production as
inclusion bodies; including cost and time savings, and reduction of endotoxin.
Signal peptides play an important role in targeting proteins for translocation
across the cytoplasmic membrane to the periplasmic space and release into culture
medium during the secretion process. Alpha toxinH35L (ATH35L) was selected as an
antigen for vaccine development against Staphylococcus aureus infections. It was
successfully secreted into culture medium of E. coli by using bacterial signal
peptides linked to the N-terminus of the protein. In order to improve the level
of secreted ATH35L, we designed a series of novel signal peptides by swapping
individual domains of modifying dsbA and pelB signal peptides and tested them in
a fed-batch fermentation process. The data showed that some of the modified
signal peptides improved the secretion efficiency of ATH35L compared with E. coli
signal peptides from dsbA, pelB and phoA proteins. Indeed, one of the novel
signal peptides improved the yield of secreted ATH35L by 3.5-fold in a fed-batch
fermentation process and at the same time maintained processing at the expected
site for signal peptide cleavage. Potentially, these new novel signal peptides
can be used to improve the secretion efficiency of other heterologous proteins in
E. coli. Furthermore, analysis of the synthetic signal peptide amino acid
sequences provides some insight into the sequence features within the signal
peptide that influence secretion efficiency.
PMID- 28497289
TI - Systematic analysis of the lysine acetylome reveals diverse functions of lysine
acetylation in the oleaginous yeast Yarrowia lipolytica.
AB - Lysine acetylation of proteins, a major post-translational modification, plays a
critical regulatory role in almost every aspects in both eukaryotes and
prokaryotes. Yarrowia lipolytica, an oleaginous yeast, is considered as a model
for bio-oil production due to its ability to accumulate a large amount of lipids.
However, the function of lysine acetylation in this organism is elusive. Here, we
performed a global acetylproteome analysis of Y. lipolytica ACA-DC 50109. In
total, 3163 lysine acetylation sites were identified in 1428 proteins, which
account for 22.1% of the total proteins in the cell. Fifteen conserved
acetylation motifs were detected. The acetylated proteins participate in a wide
variety of biological processes. Notably, a total of 65 enzymes involved in lipid
biosynthesis were found to be acetylated. The acetylation sites are distributed
in almost every type of conserved domains in the multi-enzymatic complexes of
fatty acid synthetases. The provided dataset probably illuminates the crucial
role of reversible acetylation in oleaginous microorganisms, and serves as an
important resource for exploring the physiological role of lysine acetylation in
eukaryotes.
PMID- 28497290
TI - Medium-chain-length polyhydroxyalkanoates synthesis by Pseudomonas putida KT2440
relA/spoT mutant: bioprocess characterization and transcriptome analysis.
AB - Pseudomonas putida KT2440 is a model bacteria used commonly for medium-chain
length polyhydroxyalkanoates (mcl-PHAs) production using various substrates.
However, despite many studies conducted on P. putida KT2440 strain, the molecular
mechanisms of leading to mcl-PHAs synthesis in reaction to environmental stimuli
are still not clear. The rearrangement of the metabolism in response to
environmental stress could be controlled by stringent response that modulates the
transcription of many genes in order to promote survival under nutritional
deprivation conditions. Therefore, in this work we investigated the relation
between mcl-PHAs synthesis and stringent response. For this study, a relA/spoT
mutant of P. putida KT2440, unable to induce the stringent response, was used.
Additionally, the transcriptome of this mutant was analyzed using RNA-seq in
order to examine rearrangements of the metabolism during cultivation. The results
show that the relA/spoT mutant of P. putida KT2440 is able to accumulate mcl-PHAs
in both optimal and nitrogen limiting conditions. Nitrogen starvation did not
change the efficiency of mcl-PHAs synthesis in this mutant. The transition from
exponential growth to stationary phase caused significant upregulation of genes
involved in transport system and nitrogen metabolism. Transcriptional regulators,
including rpoS, rpoN and rpoD, did not show changes in transcript abundance when
entering the stationary phase, suggesting their limited role in mcl-PHAs
accumulation during stationary phase.
PMID- 28497291
TI - Two early eudicot fossil flowers from the Kamikitaba assemblage (Coniacian, Late
Cretaceous) in northeastern Japan.
AB - Two new fossil taxa referable to the basal eudicot grade are described from the
Kamikitaba locality (ca. 89 MYBP, early Coniacian: Late Cretaceous) of the Futaba
Group in Japan. These charcoalified mesofossils exhibit well-preserved three
dimensional structure and were analyzed using synchrotron-radiation X-ray
microtomography to document their composition and internal structure. Cathiaria
japonica sp. nov. is represented by infructescence segments that consist of an
axis bearing three to four fruits. The capsular fruits are sessile and dehiscent
and consist of a gynoecium subtended by a bract. No perianth parts are present.
The gynoecium is monocarpellate containing two pendulous seeds. The carpel is
ascidiate in the lower half and conduplicate in the upper part, and the style is
deflected abaxially with a large, obliquely decurrent stigma. Pollen grains are
tricolpate with a reticulate exine. The morphological features of Cathiaria are
consistent with an assignment to the Buxaceae s. l. (including Didymelaceae).
Archaestella verticillatus gen. et sp. nov. is represented by flowers that are
small, actinomorphic, pedicellate, bisexual, semi-inferior, and multicarpellate.
The floral receptacle is cup shaped with a perigynous perianth consisting of
several tepals inserted around the rim. The gynoecium consists of a whorl of ten
conduplicate, laterally connate but distally distinct carpels with a conspicuous
dorsal bulge, including a central cavity. The styles are short, becoming recurved
with a ventrally decurrent stigma. Seeds are ca. 10 per carpel, marginal,
pendulous from the broad, oblique summit of the locule. Pollen grains are
tricolpate with a reticulate exine pattern, suggesting a relationship to
eudicots. The morphological features of Archaestella indicate a possible
relationship to Trochodendraceae in the basal grade of eudicots. The fossil
currently provides the earliest record of the family and documents the presence
of Trochodendraceae in eastern Eurasia during the middle part of the Late
Cretaceous.
PMID- 28497292
TI - Cancer subtypes in aetiological research.
AB - Researchers often attempt to categorize tumors into more homogeneous subtypes to
better predict prognosis or understand pathogenic mechanisms. In clinical
research, typically the focus is on prognosis: the tumor subtypes are intended to
be associated with specific responses to treatment and/or different clinical
outcomes. In aetiological research, the focus is on identifying distinct
pathogenic mechanisms, which may involve different risk factors. We used directed
acyclic graphs to present a framework for considering potential biases arising in
aetiological research of tumor subtypes, when there is incomplete correspondence
between the identified subtypes and the underlying pathogenic mechanisms. We
identified two main scenarios: (1) weak effect, when the tumor subtypes are
identified through combinations of characteristics and some of these
characteristics are affected by factors that are unrelated with the underlying
pathogenic mechanisms; and (2) lack of causality, when the set of characteristics
corresponds with a mechanism that is actually not a cause of the tumor of
interest. Examples of the magnitude of bias that can be introduced in these
situations are provided. Although categorization of tumors into homogenous
subtypes may have important implications for aetiological research and
identification of risk factors, the characteristics used to classify tumors into
subtypes should be as close as possible to the actual pathogenic mechanisms to
avoid interpretative biases. Whenever our knowledge of these mechanisms is
limited, research into risk factors for tumor subtypes should first aim to
causally link the characteristics to the pathogenic mechanisms.
PMID- 28497293
TI - Calcium Oscillation Frequency-Sensitive Gene Regulation and Homeostatic
Compensation in Pancreatic beta-Cells.
AB - Pancreatic islet [Formula: see text]-cells are electrically excitable cells that
secrete insulin in an oscillatory fashion when the blood glucose concentration is
at a stimulatory level. Insulin oscillations are the result of cytosolic
[Formula: see text] oscillations that accompany bursting electrical activity of
[Formula: see text]-cells and are physiologically important. ATP-sensitive
[Formula: see text] channels (K(ATP) channels) play the key role in setting the
overall activity of the cell and in driving bursting, by coupling cell metabolism
to the membrane potential. In humans, when there is a defect in K(ATP) channel
function, [Formula: see text]-cells fail to respond appropriately to changes in
the blood glucose level, and electrical and [Formula: see text] oscillations are
lost. However, mice compensate for K(ATP) channel defects in islet [Formula: see
text]-cells by employing alternative mechanisms to maintain electrical and
[Formula: see text] oscillations. In a recent study, we showed that in mice
islets in which K(ATP) channels are genetically knocked out another [Formula: see
text] current, provided by inward-rectifying [Formula: see text] channels, is
increased. With mathematical modeling, we demonstrated that a sufficient
upregulation in these channels can account for the paradoxical electrical
bursting and [Formula: see text] oscillations observed in these [Formula: see
text]-cells. However, the question of determining the correct level of
upregulation that is necessary for this compensation remained unanswered, and
this question motivates the current study. [Formula: see text] is a well-known
regulator of gene expression, and several examples have been shown of genes that
are sensitive to the frequency of the [Formula: see text] signal. In this
mathematical modeling study, we demonstrate that a [Formula: see text]
oscillation frequency-sensitive gene transcription network can adjust the gene
expression level of a compensating [Formula: see text] channel so as to rescue
electrical bursting and [Formula: see text] oscillations in a model [Formula: see
text]-cell in which the key K(ATP) current is removed. This is done without the
prescription of a target [Formula: see text] level, but evolves naturally as a
consequence of the feedback between the [Formula: see text]-dependent enzymes and
the cell's electrical activity. More generally, the study indicates how [Formula:
see text] can provide the link between gene expression and cellular electrical
activity that promotes wild-type behavior in a cell following gene knockout.
PMID- 28497294
TI - A two-step deconvolution-analysis-informed population pharmacodynamic modeling
approach for drugs targeting pulsatile endogenous compounds.
AB - Pharmacodynamic modeling of pulsatile endogenous compounds (e.g. growth hormone
[GH]) is currently limited to the identification of a low number of pulses.
Commonly used pharmacodynamic models are not able to capture the complexity of
pulsatile secretion and therefore non-compartmental analyses are performed to
extract summary statistics (mean, AUC, Cmax). The aim of this study was to
develop a new quantification method that deals with highly variable pulsatile
data by using a deconvolution-analysis-informed population pharmacodynamic
modeling approach. Pulse frequency and pulse times were obtained by deconvolution
analysis of 24 h GH profiles. The estimated pulse times then informed a non
linear mixed effects population pharmacodynamic model in NONMEM V7.3. The
population parameter estimates were used to perform simulations that show
agonistic and antagonistic drug effects on the secretion of GH. Additionally, a
clinical trial simulation shows the application of this method in the
quantification of a hypothetical drug effect that inhibits GH secretion. The GH
profiles were modeled using a turnover compartment in which the baseline
secretion, kout, pulse secretion width, amount at time point 0 and pulse
amplitude were estimated as population parameters. Population parameters were
estimated with low relative standard errors (ranging from 2 to 5%). Total body
water (%) was identified as a covariate for pulse amplitude, baseline secretion
and the pulse secretion width following a power relationship. Simulations
visualized multiple gradients of a hypothetical drug that influenced the
endogenous secretion of GH. The established model was able to fit and quantify
the highly variable individual 24 h GH profiles over time. This pharmacodynamic
model can be used to quantify drug effects that target other endogenous pulsatile
compounds.
PMID- 28497295
TI - Assessing the risk and disease burden of Clostridium difficile infection among
patients with hospital-acquired pneumonia at a University Hospital in Central
China.
AB - PURPOSE: Hospital-acquired pneumonia (HAP) remains one of the major hospital
acquired infections in China. Antibiotic treatment of HAP may lead to subsequent
Clostridium difficile infection (CDI). Baseline data on the occurrence of CDI
among HAP patients in China are currently unavailable. This study examines the
risk and disease burden of CDI among HAP hospitalized patients (HAP-CDI).
METHODS: We conducted a prospective study among ICU patients with HAP and
hospital-onset diarrhea from January 2014 to December 2014 in a teaching hospital
in China. All stool specimens were cultured for C. difficile which were typed by
MLST. We used univariate and multivariable regression analyses to identify risk
factors of HAP-CDI. FINDINGS: In total, 369 patients who met the inclusion
criteria were enrolled. Thirty-two patients tested C. difficile positive. Among
the isolated C. difficile strains, 90.63% (29/32) isolates were toxinogenic.
Various MLST types were identified. The incidence of HAP-CDI was 11.67/10,000
patient days (95% CI, 7.97-16.55). Nineteen patients died from complications. The
attributable mortality rate was 5.15% (19/369). The mortality rate of HAP-CDI
group was 13.79% which was higher than HAP-non-CDI group. Univariate analyses
demonstrated that old age, receiving antibiotics (OR = 8.70) and glucocorticoids
(OR = 7.71) 1 month prior to hospitalization, respiratory failure (OR = 3.28) and
receiving antimicrobials during hospitalization (OR = 1.15) were the risk factors
associated with CDI. Multivariate conditional logistic regression analysis
demonstrated the similar results. CONCLUSION: CDI was common among patients
discharged from hospital for HAP at a university hospital. Prevention of the
spreading of C. difficile among hospitalized patients is urgently needed.
PMID- 28497296
TI - Preferential flow characteristics of reclaimed mine soils in a surface coal mine
dump.
AB - There are a large number of macropores/tubular channels of a few centimeters and
plant roots in reclaimed dump soils, which are the main reasons for the formation
of soil macropores and soil preferential flow. To systematically study the
morphological characteristics and variation of soil preferential flow for
different reclaimed vegetations in a dump, a dye-staining experiment and physical
and chemical analysis were carried out to investigate the formation mechanism and
influencing factors of soil preferential flow in the vegetation restoration
process. The results indicate that there were differences in the soil water
breakthrough curves for different plots. The macropore effluent rate generally
increased at first and then tended to stabilize. The soil steady effluent rate
decreased with increasing soil depth, which reached the maximum and minimum
values at the depths of 0~5 cm (0.0193~0.0315 mm s-1) and 50~60 cm (0.0028~0.0035
mm s-1), respectively. Furthermore, the radius of soil macropores under different
types of reclaimed vegetation ranged from 0.03 to 4.71 mm, most of which ranged
from 0.11 to 2.36 mm. The soil macroporosity of different reclaimed vegetation
types ranged from 0.03 to 16.58%, which was significantly greater than 5%. The
soil macroporosity determined 65% of the variation in the steady effluent rate
and 42% of the variation in the saturated hydraulic conductivity. Furthermore,
the dye coverage ratio decreased as the soil layer depth increased in different
plots, and there were some differences in each plot. The maximum dye coverage
ratio occurred in the 0~5 cm soil layer, which reached 90.37%. The dye coverage
ratio at a depth of 0~60 cm in six plots followed the order of Robinia
pseudoacacia (26.48%) > Ulmus pumila (20.12%) > mixed forest (17.32%) > farmland
(15.06%) > shrub (13.97%) > weeds (10.07%). The soil preferential flow mostly
occurred in the 0~40 cm soil depth layer, which occupied more than 93% of the
total soil profile (0~60 cm). Moreover, a Pearson correlation was used to analyze
the relationship between environmental factors (soil, water, and plant factors)
and the dye coverage ratio. The dye coverage ratio of soil preferential flow
under different reclamation vegetations was very significantly or significantly
positively correlated with the gravel content, mean radius of soil macropores,
soil saturated hydraulic conductivity, root weight density, and root length
density, which promoted the formation and development of soil preferential flow.
This study will provide a scientific basis for understanding the formation
mechanism and perfecting the research system of soil preferential flow,
vegetation restoration, and reconstruction in a dump; furthermore, this research
offers significance guidance in the construction of green mines and the
development of regional economics.
PMID- 28497298
TI - Erratum to: Changing Places, Changing Plates? A Binational Comparison of Barriers
and Facilitators to Healthful Eating Among Central American Communities.
PMID- 28497297
TI - Assessing the influence of different plant species in drainage ditches on
mitigation of non-point source pollutants (N, P, and sediments) in the Purple
Sichuan Basin.
AB - Three different types of ditches, each 300 m in length, were employed in this
study. One vegetated constructed ditch (VCD), three natural vegetated soil
ditches (NVSD), and three constructed ditches left unvegetated (UCD) as controls
were investigated using simple in/out mass balances and uptake by plant species
with a potential for phytoremediation and their mechanisms. Significant
differences in the ditches were observed, suggesting the importance of plant
species in nutrient mitigation. The removal rates of TN (total nitrogen) and TP
(total phosphorus) were 64.28 and 58.02, 31.16 and 27.49, and 3.91 and 2.97%,
respectively, in the VCD, NVSD, and UCD. Canna indica (45.12 g m-2) and Oenanthe
javanica (21.48 g m-2) had the highest total N and P storage in the VCD and NVSD.
Furthermore, species C. indica possessed the highest annual N and P uptake in the
VCD (216.59 kg N/ha/yr and 30.73 kg P/ha/yr). In the NVSD, species O. javanica
had the greatest annual N and P uptake (96.66 kg N/ha/yr and 7.94 kg P/ha/yr).
Both VCD and NVSD were found to have a reasonably good outcome compared to UCD.
Retention of nutrients by ditch sediments was probably the major attenuation
mechanism, with subsequent plant uptake and microbial nitrification
denitrification of the nutrients as secondary removal mechanisms. Results of this
study highlight the importance of taking actions for establishment of appropriate
plant species inside the ditches in order to enhance its direct and indirect
roles and maximize purification rate in aquatic environments.
PMID- 28497299
TI - Ecotoxicological and Health Risk Assessment of Polycyclic Aromatic Hydrocarbons
(PAHs) in Short-Neck Clam (Paphia undulata) and Contaminated Sediments in Malacca
Strait, Malaysia.
AB - The distribution, sources, and human health risk assessment of polycyclic
aromatic hydrocarbons (PAHs) in surface sediment and the edible tissue of short
neck clam (Paphia undulata) from mudflat ecosystem in the west coast of Malaysia
were investigated. The concentrations of ?16 PAHs varied from 347.05 to 6207.5
and 179.32 to 1657.5 ng g-1 in sediment and short-neck clam samples,
respectively. The calculations of mean PEL quotients (mean-PELQs) showed that the
ecological risk of PAHs in the sediment samples was low to moderate-high level,
whereas the total health risk through ingestion and dermal contact was
considerably high. The PAHs biota sediment accumulation factors data for short
neck clam were obtained in this study, indicating a preferential accumulation of
lower molecular weight PAHs. The source apportionment of PAHs in sediment using
positive matrix factorization model indicated that the highest contribution to
the PAHs was from diesel emissions (30.38%) followed by oil and oil derivate and
incomplete coal combustion (23.06%), vehicular emissions (16.43%), wood
combustion (15.93%), and natural gas combustion (14.2%). A preliminary evaluation
of human health risk using chronic daily intake, hazard index, benzo[a]pyrene
equivalent (BaPeq) concentration, and the incremental lifetime cancer risk
indicated that PAHs in short-neck clam would induce potential carcinogenic
effects in the consumers.
PMID- 28497300
TI - [(Partial) fusion of the wrist : Indications and surgical procedures].
AB - Carpal bone fusions for secondary reconstruction are still indispensable despite
state of the art diagnostic tools and modern treatment techniques for wrist
lesions. The former fusions stabilize the wrist and enable sufficient residual
carpal mobility. Pain can be reduced significantly by arthrodesis of destroyed
joints and the progress of osteoarthritis may be stopped or delayed. This review
presents commonly used fusions with their inherent indications, contraindications
and complications.
PMID- 28497302
TI - Keys for the morphological identification of the Australian paralysis ticks
(Acari: Ixodidae), with scanning electron micrographs.
AB - The Australian paralysis ticks (Ixodes: Sternalixodes) are of considerable
medical and veterinary importance within Australia. This is because of their
ability to cause paralysis but also their capacity to transmit pathogens and
induce allergic reactions. The available keys for the identification of the group
(Ixodes holocyclus Neumann, Ixodes cornuatus Roberts, and Ixodes hirsti Hassall)
are ambiguous and contain errors, making accurate identification of the group
difficult. Illustrations of varying quality and accuracy of these species have
been published in the past; however, they have never been collectively treated
using scanning electron microscopy (SEM). Female Australian paralysis ticks are
here examined using SEM, and the first pictorial key for this group is presented
along with an accurate text key.
PMID- 28497301
TI - Various Regulatory Modes for Circadian Rhythmicity and Sexual Dimorphism in the
Non-Neuronal Cardiac Cholinergic System.
AB - Cardiomyocytes possess a non-neuronal cardiac cholinergic system (NNCCS)
regulated by a positive feedback system; however, its other regulatory mechanisms
remain to be elucidated, which include the epigenetic control or regulation by
the female sex steroid, estrogen. Here, the NNCCS was shown to possess a
circadian rhythm; its activity was upregulated in the light-off phase via histone
acetyltransferase (HAT) activity and downregulated in the light-on phase.
Disrupting the circadian rhythm altered the physiological choline
acetyltransferase (ChAT) expression pattern. The NNCCS circadian rhythm may be
regulated by miR-345, independently of HAT, causing decreased cardiac ChAT
expression. Murine cardiac ChAT expression and ACh contents were increased more
in female hearts than in male hearts. This upregulation was downregulated by
treatment with the estrogen receptor antagonist tamoxifen, and in contrast,
estrogen reciprocally regulated cardiac miR-345 expression. These results suggest
that the NNCCS is regulated by the circadian rhythm and is affected by sexual
dimorphism.
PMID- 28497303
TI - Review of cattle ticks (Acari, Ixodida) in Ivory Coast and geographic
distribution of Rhipicephalus (Boophilus) microplus, an emerging tick in West
Africa.
AB - The exotic tick Rhipicephalus (Boophilus) microplus was discovered in Ivory Coast
in 2007 and then gradually in other countries in West Africa. It is known to
induce significant losses in farming and to replace other species of the same
genus. In order to contribute to improve health and productivity of cattle in
Ivory Coast regarding the emergence of this dreaded tick, a study was conducted
to determine the current geographic distribution of the tick R. (B.) microplus
and review cattle ticks in general. To this end, 23,460 ticks were collected from
180 farms located throughout the country. Ten species of ticks belonging to the
genus Rhipicephalus (including those of the subgenus Boophilus), Hyalomma and
Ambyomma were identified. It was found that the exotic tick R. (B.) microplus has
invaded the entire Ivorian territory and is now the main cattle tick (63.6% of
ticks collected), followed by Amblyomma variegatum that remains still dominant in
the North. The population of indigenous species of Rhipicephalus (Boophilus) is
in drastic decline.
PMID- 28497304
TI - Acaricidal activity of Havardia albicans and Caesalpinia gaumeri methanolic leaf
extracts on Rhipicephalus microplus and its toxicity to laboratory animals.
AB - The acaricidal activity of methanolic extracts from the leaves of Havardia
albicans (Kunth Britton and Rose) and Caesalpinia gaumeri (Greenm) were tested on
the larvae and adults of the cattle tick Rhipicephalus microplus Canestrini using
the larval immersion test and the adult immersion test, respectively. The
toxicity of these extracts was also evaluated on laboratory animals using
toxicity bioassays at different concentrations: skin irritability (500 mg/ml),
acute oral toxicity (5000 mg/kg), ocular irritability (1000 mg/ml) and dermal
toxicity (5000 mg/kg). The acaricidal activity of the H. albicans extracts on R.
microplus larvae showed a LC50 of 7.0% (4.3-11.4) and a LC99 of 25.5% (14.26
201.5). The acaricidal activity of the C. gaumeri extracts on larvae showed a
LC50 of 7.8% (5.74-10.65) and a LC99 of 38.32% (22.22-146.48). The H. albicans
extracts showed moderate acaricidal activity in the inhibition of egg laying
(54.4 +/- 12.4) and the inhibition of larval hatching (48.7 +/- 6.8) in R.
microplus adults. The C. gaumeri extracts also showed moderate acaricidal
activity in the inhibition of egg laying (51.0 +/- 11.2). However, none of the
evaluated extracts showed significant toxicity on laboratory rodents. These
plants show the potential to control R. microplus and could be administered
topically or orally in animals. Further studies are needed to identify the active
compound(s) and to evaluate the effects of these plants on R. microplus in vivo.
PMID- 28497308
TI - Transient abducens nerve palsy after cervical traction.
PMID- 28497305
TI - Deep Brain Stimulation Emergencies: How the New Technologies Could Modify the
Current Scenario.
AB - After 25 years of deep brain stimulation (DBS) for the treatment of Parkinson's
disease, it has become increasingly recognized that a range of postoperative
urgent situations and emergencies may occur. In this review we describe the
possible scenarios of DBS-related emergencies: perioperative (intraoperative and
early postoperative) and postoperative settings and issues from suboptimal
control of motor and nonmotor symptoms in the early programming phase and during
long-term follow-up. We also outline potential advantages in the management of
these emergencies offered by the newest devices, emerging technologies, and new
possibilities in programming.
PMID- 28497306
TI - Triterpenoid saponins from Polaskia chichipe Backbg. and their inhibitory or
promotional effects on the melanogenesis of B16 melanoma cells.
AB - Five new oleanane-type saponins 1-5 together with a known saponin 6 and a
steroidal glycoside 7 were isolated from Polaskia chichipe Backbg., and their
structures were determined from their 1D and 2D NMR and HRFABMS spectral data.
The six isolated saponins 1-6 were tested for their effects on the melanogenesis
of B16 melanoma 4A5 cells. Compound 1 exerted an inhibitory effect at 100 MUM
whereas compound 3 promoted melanogenesis at the same concentration, even though
these two compounds contain the same aglycon structure. The dose-dependent
activities of compounds 1 and 3 on melanin synthesis were investigated.
PMID- 28497309
TI - The correlation of lymphocyte subsets, natural killer cell, and Parkinson's
disease: a meta-analysis.
AB - The correlation between immunity and Parkinson's disease was presented in many
papers, which also discussed lymphocyte and natural killer cell. But these
studies have yielded inconsistent results. To systematically review the
relationship between the lymphocyte subsets/natural killer cell and the risk of
Parkinson's disease, we electronically searched the SpringerLink, Web of Science,
Ebsco-medline with full text, Pubmed, Elsevier-ScienceDirect, Ovid-lww-oup,
Wanfang Data for case-control trials on comparing the number of peripheral blood
lymphocyte subsets and natural killer cell in Parkinson's patients and healthy
controls. According to the Cochrane methods, the reviewers selected literature,
extracted data, and assessed the quality. Then, a meta-analysis was performed
using RevMan 5.2. Finally, 21 case-control trials including 943 cases of
Parkinson's disease were fit into our data analysis. Meta-analysis showed that
the decreased numbers of CD3+, CD4+ lymphocyte subsets and the increased number
of natural killer cell were found in Parkinson's disease patients. In the
intermediate and late stage of PD, CD8+ lymphocyte subsets had a significant
decrement. However, the number of B lymphocyte subsets had no significant
association with Parkinson's disease. The lymphocyte subsets and NK cell may be
associated with the risk of Parkinson's disease.
PMID- 28497310
TI - Use of cell phones and brain tumors: a true association?
PMID- 28497311
TI - Circulating TNF-alpha levels increased and correlated negatively with IGF-I in
postoperative cognitive dysfunction.
AB - Signaling pathways of tumor necrosis factor-alpha (TNF-alpha) and insulin-like
growth factor-I (IGF-I) are found to be functionally interrelated in some
experimental studies. IGF-I may be involved in the pathogenesis of postoperative
cognitive dysfunction (POCD). In order to investigate the possible interaction of
TNF-alpha and IGF-I in POCD, the plasma levels of IGF-I and TNF-alpha were
determined in 44 patients under general anesthesia. As compared with non-POCD
patients, POCD patients showed increased TNF-alpha and decreased IGF-I levels in
plasma, as well as a significant negative correlation between TNF-alpha and IGF-I
values. The present results suggest that interaction of increased TNF-alpha
levels and decreased IGF-1 levels might lead to a vicious circle, which may
contribute to POCD.
PMID- 28497312
TI - Phenytoin: neuroprotection or neurotoxicity?
AB - Phenytoin is an 80-year young molecule and new indications are still emerging.
The neuroprotective potential of phenytoin has been evaluated for decades.
Recently, a positive phase II trial supported its further development in the
treatment of optic neuritis in multiple sclerosis. In 1942, however, peripheral
neuritis was first reported to be an adverse event of phenytoin, and since then a
small but steady stream of publications discussed peripheral polyneuropathy as
being a possible adverse event of phenytoin. We have reviewed the literature and
concluded there is some supportive evidence for a reversible polyneuropathy after
the oral use of phenytoin, though with no evidence for clear neurotoxicity on the
level of peripheral nerves. This is probably due to the fact that the
pharmacological effects of phenytoin, based on the stabilizing effect of the
voltage-gated sodium channels, make impairment of nerve conduction in
asymptomatic and symptomatic reversible polyneuropathies plausible. Clear
toxically-induced phenytoin-related polyneuropathies, however, are extremely rare
and are always related to high dose or high plasma levels of phenytoin, mostly
developing during many years of therapy. We could only find one case of a
probable reversible chronic phenytoin intoxication resulting in a biopsy proven
axonal atrophy with secondary demyelination and signs of remyelination. All case
series and case reports published are insufficient in detail to prove a clear
causal relation between phenytoin intake and the induction of a peripheral
polyneuropathy. Phenytoin does not lead to irreversible toxicity of the
peripheral nerves and might, on the other hand, have neuroprotective properties.
PMID- 28497313
TI - Lewis P. Rowland, MD.
PMID- 28497314
TI - [Legal aspects of aging].
PMID- 28497315
TI - Energy-coupling mechanism of the multidrug resistance transporter AcrB: Evidence
for membrane potential-driving hypothesis through mutagenic analysis.
PMID- 28497316
TI - Quality assurance trials for Ki67 assessment in pathology.
AB - Ki67 is a broadly used proliferation marker in surgical pathology with an obvious
need for standardization to improve reproducibility of assessment. Here, we
present results of the so far only existing round robin tests on Ki67, organized
annually in Germany, Austria, and Switzerland from 2010 to 2015 with up to 160
participating laboratories (QuIP). In each quality assessment trial, eight probes
from each breast cancer, neuroendocrine tumor, and malignant lymphoma were
compiled on a tissue microarray (TMA). TMAs were stained in the participants'
laboratories with antibodies and procedures also applied in their daily routine.
Participating pathologists were expected to assign Ki67 values to one of four
different categories for each tumor type. All local stainings and evaluations
were reassessed by the organizing panel and compared to a preset standard. On
average, 95% of participants reached the benchmark of over 80% concordance rates
with the Ki67 category pre-established by the panel. Automatization and type of
antibody did not affect the success rate. Concordance rates differed between
tumor entities being highest in each tumor type with either very high or very low
labeling indices. Lower rates were seen for intermediate Ki67 levels. Staining
quality improved during the observation period as did inter-observer concordance
with 85% of participants achieving excellent agreement (kappa > 0.8) in the first
year and over 95% in 2015. In conclusion, regular external quality assurance
trials have been established as a tool to improve the reproducibility and
reliability of the prognostic and predictive proliferation marker Ki67.
PMID- 28497317
TI - Role of Radiation Therapy in the Treatment of Hodgkin Lymphoma.
AB - Radiation therapy has historically been the pillar of curative treatment for
Hodgkin lymphoma (HL). With improved efficacy of systemic therapy and the ever
increasing recognition of treatment-related morbidity in long-term survivors, the
role of radiotherapy has evolved significantly. Modern combined modality therapy
(CMT) with multi-agent chemotherapy followed by involved site radiation therapy
(ISRT) to initially involved sites of disease remains the gold standard for the
majority of patients with HL. Reduction of long-term treatment-related toxicity
has become the major driver in clinical trial design for early-stage HL while
improved disease-specific survival remains the goal in patients with more
advanced and unfavorable disease. This review will address the data supporting
the use of radiotherapy in HL as well as specific methods for reducing late
toxicity from radiotherapy.
PMID- 28497318
TI - Controlled Ion Release from Novel Polyester/Ceramic Composites Enhances
Osteoinductivity.
AB - Due to the growing number of patients suffering from musculoskeletal defects and
the limited supply of and sub-optimal outcomes associated with biological graft
materials, novel biomaterials must be created that can function as graft
substitutes. For bone regeneration, composite materials that mimic the organic
and inorganic phases of natural bone can provide cues which expedite and enhance
endogenous repair. Specifically, recent research has shown that calcium and
phosphate ions are inherently osteoinductive, so controllably delivering their
release holds significant promise for this field. In this study, unique aliphatic
polyesters were synthesized and complexed with a rapidly decomposing ceramic
(monobasic calcium phosphate, MCP) yielding novel polymer/ceramic composite
biomaterials. It was discovered that the fast dissolution and rapid burst release
of ions from MCP could be modulated depending on polymer length and chemistry.
Also, controlled ion release was found to moderate solution pH associated with
polyester degradation. When composite biomaterials were incubated with
mesenchymal stems cells (MSCs) they were found to better facilitate osteogenic
differentiation than the individual components as evidenced by increased alkaline
phosphate expression and more rapid mineralization. These results indicate that
controlling calcium and phosphate ion release via a polyester matrix is a
promising approach for bone regenerative engineering.
PMID- 28497319
TI - Trends in and relation between hip fracture incidence and osteoporosis medication
utilization and prices in Estonia in 2004-2015.
AB - : Osteoporosis medicines reduce osteoporotic fractures. There is a very strong
negative correlation between the consumption of medicines and the price of an
average daily dose indicating that affordability is a key factor that could
increase consumption of antiosteoporotic medicines and, through that, reduce
fractures. PURPOSE: Osteoporosis is a major cause of morbidity and mortality in
the modern world. Our study aims to describe the trends in incidence of hip
fractures in relation to drug utilization patterns and the average price of
antiosteoporotic medicines in Estonia. METHODS: Data on hip fractures was
obtained from the medical claims database of Estonian Health Insurance Fund
(EHIF). Consumption and price data was obtained from the Estonian State Agency of
Medicines (SAM).Consumption is presented using WHO defined daily doses
methodology, and the prices reflect the average wholesale price of medicines.
RESULTS: From 2004 to 2010 there was a non-significant increasing trend in
standardized hip fracture incidence in Estonia, but from 2010 to 2015, the trend
turned to a significant decrease of 4.5% per year. The consumption of
osteoporosis medication increased significantly from 2004 to 2009 by yearly
average of 41.2%. After 2009, the consumption levelled. On contrast, the average
price of one daily dose of osteoporosis medication decreased significantly from
2004 to 2009 by 16.9% per year and the decrease also levelled after 2009. This
gives a very strong negative correlation of -0.93 (p < 0.001) between the
consumption of antiosteoporotic medication and the average price of a daily dose
of medication during the study period. CONCLUSIONS: The statistically significant
decline of standardized incidence of hip fractures from 2010 onward could at
least in part be the result of the high increase in consumption of
antiosteoporotic medicines which in turn is strongly negatively correlated with
the average price of osteoporosis medicines.
PMID- 28497320
TI - Accelerating drug development by efficiently using emerging PK/PD data from an
adaptable entry-into-human trial: example of lumretuzumab.
AB - PURPOSE: This study aimed at evaluating if pharmacokinetic and pharmacodynamic
data from the first few patients treated with an investigational monoclonal
antibody in a dose-escalation study can be used to guide the early initiation of
potentially more efficacious combination regimens. METHODS: Emerging
pharmacokinetic and pharmacodynamic data from the first nine patients treated
with lumretuzumab (a glycoengineered anti-HER3 monoclonal antibody) monotherapy
at doses from 100 to 400 mg q2w were used along with a pharmacokinetic model that
incorporated target-mediated drug disposition to guide the selection of the
starting dose for use in combination regimens. RESULTS: The dose-escalation study
investigated lumretuzumab doses up to 2000 mg q2w and a maximum tolerated dose
was not reached. However, the model described in this report predicted linear
lumretuzumab pharmacokinetics and >95% target saturation at doses >=400 mg q2w.
These data, along with safety data, contributed to the decision to begin dose
escalation studies in combination with cetuximab and erlotinib using a starting
dose of 400 mg lumretuzumab. Pharmacokinetic data from patients treated with
lumretuzumab 400-2000 mg q2w in combination regimens were consistent with the
model predictions. CONCLUSION: PK/PD modelling of emerging clinical data might
accelerate development programs by enabling additional parts of a trial to
commence before completion of the monotherapy part. The dose and schedule of
lumretuzumab were optimised for concomitant therapy at doses substantially below
the highest dose investigated.
PMID- 28497322
TI - Oral and video presentations.
PMID- 28497321
TI - Predicting Cumulative and Maximum Brain Strain Measures From HybridIII Head
Kinematics: A Combined Laboratory Study and Post-Hoc Regression Analysis.
AB - Due to growing concern on brain injury in sport, and the role that helmets could
play in preventing brain injury caused by impact, biomechanics researchers and
helmet certification organizations are discussing how helmet assessment methods
might change to assess helmets based on impact parameters relevant to brain
injury. To understand the relationship between kinematic measures and brain
strain, we completed hundreds of impacts using a 50th percentile Hybrid III head
neck wearing an ice hockey helmet and input three-dimensional impact kinematics
to a finite element brain model called the Simulated Injury Monitor (SIMon) (n =
267). Impacts to the helmet front, back and side included impact speeds from 1.2
to 5.8 ms-1. Linear regression models, compared through multiple regression
techniques, calculating adjusted R 2 and the F-statistic, determined the most
efficient set of kinematics capable of predicting SIMon-computed brain strain,
including the cumulative strain damage measure (specifically CSDM-15) and maximum
principal strain (MPS). Resultant change in angular velocity, Deltaomega R,
better predicted CSDM-15 and MPS than the current helmet certification metric,
peak g, and was the most efficient model for predicting strain, regardless of
impact location. In nearly all cases, the best two-variable model included peak
resultant angular acceleration, alpha R, and Deltaomega R.
PMID- 28497323
TI - Why null results do not mean no results: negative findings have implications for
policy, practice, and research.
PMID- 28497324
TI - Erratum to: The Presence of Norovirus and Adenovirus on Environmental Surfaces in
Relation to the Hygienic Level in Food Service Operations Associated with a
Suspected Gastroenteritis Outbreak.
PMID- 28497325
TI - The effect of pressure-controlled inverse ratio ventilation on lung protection in
obese patients undergoing gynecological laparoscopic surgery.
AB - SPECIFIC AIM: To examine the effects of pressure-controlled inverse ratio
ventilation (PCIRV) and volume-control ventilation (VCV) on arterial oxygenation,
pulmonary function, hemodynamics, levels of surfactant protein A (SP-A), and
tumor necrosis factor-alpha (TNF-alpha) in obese patients undergoing
gynecological laparoscopic surgery. METHODS: Sixty patients, body mass index
(BMI) >=30 kg/m2, scheduled for elective gynecological laparoscopic surgery were
enrolled in the study. Patients were randomly allocated to receive either PCIRV
with an inspiratory-expiratory (I:E) ratio of 1.5:1 (PCIRV group n = 30) or VCV
with an I:E ratio of 1:2 (VCV group n = 30). Ventilation variables, viz. tidal
volume (V T), dynamic respiratory-system compliance (C RS), driving pressure
(DeltaP = V T/C RS), arterial blood oxygen partial pressure/fraction of
inspiration oxygen (PaO2/FiO2) and arterial blood carbon dioxide partial pressure
(PaCO2), were measured. Hemodynamic variables, viz. mean arterial pressure (MAP),
heart rate (HR), and serum levels of SP-A and TNF-alpha, were also measured.
RESULTS: When compared to patients in the VCV group, patients in the PCIRV group
had higher V T, dynamic CRS, and PaO2/FiO2, and lower DeltaP and PaCO2 at 20 and
60 min after the start of pneumoperitoneum (p < 0.05). Patients in the PCIRV
group had lower SP-A and TNF-alpha levels at 24 and 48 h after surgery than those
in the VCV group (p < 0.05). CONCLUSION: In obese patients undergoing
gynecological laparoscopic surgery, PCIRV can improve ventilation, promote gas
exchange and oxygenation, and is associated with decreased levels of SP-A and TNF
alpha. These effects demonstrate improved lung protection provided by PCIRV in
this patient population.
PMID- 28497326
TI - Evaluation of pelvic inflammatory disease potential in cholinesterase inhibitor
pesticide-exposed females.
AB - Cholinesterase inhibitor pesticides, mainly organophosphates and carbamates, are
commonly used in Egypt. Chronic exposure of males and females working in
agriculture is expected. The study aimed to relate exposure to cholinesterase
inhibitor pesticides to the development of pelvic inflammatory disease (PID).
This is a case-control study that was conducted among 84 females. Seventy
patients complained of pelvic inflammatory disease visited the outpatient
Gynecology and Obstetrics Clinic. Fourteen females were not suffering from PID
and were chosen as a control group. Red blood cells' cholinesterase activity was
measured in blood. Cervical swaps were collected, and cultures were submitted for
microbiological examination. The results showed that cholinesterase activities
were significantly depressed in exposed females (6.36 +/- 0.8 MUmoles/min/ml red
cells) when compared to non-exposed (7.5 +/- 1.2 MUmoles/min/ml red cells), and
both were significantly depressed when compared with healthy females (9.17 +/-
0.7 MUmoles/min/ml red cells). The correlation coefficient (r) between previous
exposure and the laboratory confirmed cervical infection was 0.31, with a P value
of 0.009. The study concluded that exposure to cholinesterase inhibitor
pesticides could increase the occurrence of pelvic inflammatory disease.
PMID- 28497328
TI - Overexploitation of karst spring as a measure against water scarcity.
AB - Water scarcity, especially in the hydrologically critical part of the year, is a
problem often present in many cities and regions, particularly in arid and sub
arid areas. Climate change and human water demand compound the problem. This
paper discusses a climate change adaptation measure-the possibility of karst
spring overexploitation, where there is a siphon-shaped cavity inside the
mountain. The pilot area is near the city of Nis, where a decreasing
precipitation trend has already been observed and is expected to continue in the
future. The paper also presents some basic information related to the pilot area
and undertaken investigations. The project, successfully implemented in 2004, has
provided the city of Nis with an additional amount of 200 l/s of spring water
during the most critical part of the year.
PMID- 28497327
TI - Variation in Cd accumulation among radish cultivars and identification of low-Cd
cultivars.
AB - Heavy metals have serious health consequences and ecosystem impacts. A pot
experiment was conducted to investigate the variation of cadmium (Cd) uptake and
accumulation among 40 cultivars of radish (Raphanus sativus L.) at three Cd
levels, including 0.31 (T1), 0.83 (T2), and 1.13 (T3) mg kg-1. Most of the tested
cultivars had higher taproot biomass in the T3 treatment when compared to those
in the T1 treatment, indicating a Cd stress-induced growth in radish. Taproot Cd
concentrations in 95 and 5% of the tested cultivars were lower than 0.1 mg kg-1
(fresh weight, FW) in the T1 and T2 treatments, respectively; however, there was
no cultivar suitable for safe consumption in the T3 treatment. Radish production
showed potential risk of Cd pollution as high as some leafy vegetables when grown
in the soils where Cd concentration exceeded 0.8 mg kg-1. When compared with
Chinese heat-resisting or imported cultivars, Chinese common cultivars had
significantly higher taproot Cd concentrations. Three low-Cd cultivars and five
high-Cd cultivars were identified. Taproot Cd concentrations showed significant
correlations between any two of the three treatments (p < 0.01), suggesting that
Cd accumulation in taproot of radish was genotype-dependent.
PMID- 28497329
TI - Effect of cadmium on cytosine hydroxymethylation in gastropod hepatopancreas.
AB - 5-Hydroxymethylcytosine (5hmC) is an important, yet poorly understood epigenetic
DNA modification, especially in invertebrates. Aberrant genome-wide 5hmC levels
have been associated with cadmium (Cd) exposure in humans, but such information
is lacking for invertebrate bioindicators. Here, we aimed to determine whether
this epigenetic mark is present in DNA of the hepatopancreas of the land snail
Cantareus aspersus and is responsive to Cd exposure. Adult snails were reared
under laboratory conditions and exposed to graded amounts of dietary cadmium for
14 days. Weight gain was used as a sublethal endpoint, whereas survival as a
lethal endpoint. Our results are the first to provide evidence for the presence
of 5hmC in DNA of terrestrial mollusks; 5hmC levels are generally low with the
measured values falling below 0.03%. This is also the first study to investigate
the interplay of Cd with DNA hydroxymethylation levels in a non-human animal
study system. Cadmium retention in the hepatopancreas of C. aspersus increased
from a dietary Cd dose of 1 milligram per kilogram dry weight (mg/kg d. wt). For
the same treatment, we identified the only significant elevation in percentage of
samples with detectable 5hmC levels despite the lack of significant mortalities
and changes in weight gain among treatment groups. These findings indicate that
5hmC is an epigenetic mark that may be responsive to Cd exposure, thereby opening
a new aspect to invertebrate environmental epigenetics.
PMID- 28497330
TI - Development of nanoemulsion from Vitex negundo L. essential oil and their
efficacy of antioxidant, antimicrobial and larvicidal activities (Aedes aegypti
L.).
AB - It is believed that nanoemulsions were emerged as a promising candidate to
improve the qualities of natural essential oil towards antimicrobial and
insecticidal applications. In the present study, we have focused on the
encapsulation of Vitex negundo L. leaf essential oil using Polysorbate80 for its
different biological activities including antioxidant, bactericidal and
larvicidal activity against dengue fever vector Aedes aegypti L. Initially, the
nanoemulsion was prepared by low energy method and droplet size of the formulated
nanoemulsion was characterized by using Dynamic Light Scattering analysis. The
freshly prepared V. negundo essential nanoemulsion was observed with the mean
droplet size of below 200 nm indicating its excellent stability. Further, the
larvicidal activity of essential oil and nanoemulsion with various concentrations
(25, 50, 100, 200 and 400 ppm). The larvicidal activities were tested 2nd and 3rd
instar larval mortality rate that was observed against the 12 and 24 h exposure
period. After a 12 h exposure period, the larvicidal activities of 2nd instar
larva were observed as essential oil (73.33 +/- 1.88), nanoemulsion (81.00 +/-
0.88) and the larvicidal activities of 3rd instar larva were displayed essential
oil (70.33 +/- 2.60) and nanoemulsion (79.00 +/- 3.70). Likewise, after a 24 h
exposure period, the larvicidal activities of 2nd instar larva were observed as
essential oil (90.30 +/- 2.15), nanoemulsion (94.33 +/- 1.20) and the larvicidal
activities of 3rd instar larva were essential oil (80.66 +/- 0.66) and
nanoemulsion (93.00 +/- 1.25) respectively. We finally concluded that the
developed plant-based emulsion essential oil systems were thermodynamically
stable. Owing to its improved bioavailability and biocompatibility, formulated
nanoemulsion can be used in various biomedical applications including drug
delivery as well as disease transmitting mosquito vector control. Graphical
abstract ?.
PMID- 28497331
TI - Zingiber cernuum (Zingiberaceae) essential oil as effective larvicide and
oviposition deterrent on six mosquito vectors, with little non-target toxicity on
four aquatic mosquito predators.
AB - Mosquitoes are responsible for the transmission of many pathogens and parasites,
which cause serious diseases in humans and animals. Currently, botanical products
have been suggested as alternative tools in the fight against arthropod vectors.
In this study, the essential oil (EO) extracted from Zingiber cernuum was tested
as larvicide and oviposition deterrent on six mosquito species of public health
relevance, including malaria and Zika virus vectors. The EO showed high toxicity
on third instar larvae of Anopheles stephensi (LC50 = 41.34 MUg/ml), Aedes
aegypti (LC50 = 44.88 MUg/ml), Culex quinquefasciatus (LC50 = 48.44 MUg/ml),
Anopheles subpictus (LC50 = 51.42 MUg/ml), Aedes albopictus (LC50 = 55.84
MUg/ml), and Culex tritaeniorhynchus (LC50 = 60.20 MUg/ml). In addition, low
doses of Z. cernuum EO reduced oviposition rates in six mosquito species. The
acute toxicity of Z. cernuum EO on four mosquito predators was scarce; LC50
ranged from 3119 to 11,233 MUg/ml. Overall, our results revealed that the Z.
cernuum EO can be considered for the development of effective and environmental
friendly mosquito larvicides and oviposition deterrents.
PMID- 28497332
TI - Toxicity of nickel to soil microbial community with and without the presence of
its mineral collectors-a calorimetric approach.
AB - The toxicity of nickel and three of its main collectors, sodium isopropyl
xanthate (SIPX), sodium ethyl xanthate (SEX), and potassium ethyl xanthate (PEX)
to soil microbial activity, was analyzed, individually and as a binary
combination of nickel and each of the collectors. The investigation was performed
through the microcalorimetric analysis method. For the single chemicals, all
power-time curves exhibited lag, exponential, stationary, and death phases of
microbial growth. Different parameters exhibited a significant adverse effect of
the analyzed chemicals on soil microbial activity, with a positive relationship
between the inhibitory ratio and the chemical dose (p < 0.05 or p < 0.01). A peak
power reduction level of 24.23% was noted for 50 MUg g-1 soil in the case of Ni
while for the mineral collectors, only 5 MUg g-1 soil and 50 MUg g-1 soil induced
a peak power reduction level of over 35 and 50%, respectively, in general. The
inhibitory ratio ranged in the following order: PEX > SEX > SIPX > Ni. Similar
behavior was observed with the mixture toxicity whose inhibitory ratio
substantially decreased (maximum decrease of 38.35%) and slightly increased
(maximum increase of 15.34%), in comparison with the single toxicity of mineral
collectors and nickel, respectively. The inhibitory ratio of the mixture toxicity
was positively correlated (p < 0.05 or p < 0.01) with the total dose of the
mixture. In general, the lesser and higher toxic effects are those of mixtures
containing SIPX and PEX, respectively.
PMID- 28497334
TI - Short Overview.
AB - Mitochondrial autophagy (mitophagy) is a mitochondrial quality control mechanism
that selectively removes damaged mitochondria via autophagic degradation.
Autophagic adaptor/receptor proteins contribute to the selective degradation of
damaged mitochondria by autophagy. A part of them containing both ubiquitin
binding domains and Atg8 interacting motif (AIM)/LC3 interacting region (LIR)
motifs, which bind to the autophagy-related protein 8 (Atg8) family (LC3 and
GABARAP family), lead ubiquitylated (damaged) mitochondria to selective removal.
On the other hand, some specific outer mitochondrial membrane-anchored proteins
containing AIM/LIR motif function as another type of autophagy adaptor/receptor
proteins. Here I briefly summarize mechanisms of mitophagy and its related
proteins.
PMID- 28497333
TI - Next-Generation Sequencing-based genomic profiling of brain metastases of primary
ovarian cancer identifies high number of BRCA-mutations.
AB - Ovarian cancer represents the most common gynaecological malignancy and has the
highest mortality of all female reproductive cancers. It has a rare predilection
to develop brain metastases (BM). In this study, we evaluated the mutational
profile of ovarian cancer metastases through Next-Generation Sequencing (NGS)
with the aim of identifying potential clinically actionable genetic alterations
with options for small molecule targeted therapy. Library preparation was
conducted using Illumina TruSight Rapid Capture Kit in combination with a cancer
specific enrichment kit covering 94 genes. BRCA-mutations were confirmed by using
TruSeq Custom Amplicon Low Input Kit in combination with a custom-designed BRCA
gene panel. In our cohort all eight sequenced BM samples exhibited a multitude of
variant alterations, each with unique molecular profiles. The 37 identified
variants were distributed over 22 cancer-related genes (23.4%). The number of
mutated genes per sample ranged from 3 to 7 with a median of 4.5. The most
commonly altered genes were BRCA1/2, TP53, and ATM. In total, 7 out of 8 samples
revealed either a BRCA1 or a BRCA2 pathogenic mutation. Furthermore, all eight BM
samples showed mutations in at least one DNA repair gene. Our NGS study of BM of
ovarian carcinoma revealed a significant number of BRCA-mutations beside TP53,
ATM and CHEK2 mutations. These findings strongly suggest the implication of BRCA
and DNA repair malfunction in ovarian cancer metastasizing to the brain. Based on
these findings, pharmacological PARP inhibition could be one potential targeted
therapeutic for brain metastatic ovarian cancer patients.
PMID- 28497335
TI - Methods for Analyzing Sphingosine-1-Phosphate Signaling in Human and Mouse
Primary Mast Cells.
AB - Mast cells produce a potently bioactive sphingolipid metabolite sphingosine-1
phosphate (S1P) constitutively and upon activation. The ligation of S1P to its
type 2 receptor on mast cells triggers a novel downstream signaling pathway that
we discovered links activation of transcription factor signal transducer and
activator of transcription 3 to mast cell-derived chemokine release in both
humans and mice. In this chapter, we describe the methods used to study S1P
signaling in human and mouse primary mast cells.
PMID- 28497336
TI - The overlapping spectrum of flat irregular pigment epithelial detachment
investigated by optical coherence tomography angiography.
AB - PURPOSE: To describe the OCT angiography characteristics of flat irregular
pigment epithelial detachments (PEDs), an overlapping tomographic feature of
various macular disorders. METHODS: Consecutive patients with a dimpled retinal
pigment epithelium profile on OCT, referred for a second opinion, were enrolled.
Fluorescein (FA) and indocyanine green angiography (ICGA) were performed in all
patients and compared to previous examinations, when available. In all patients,
enhanced depth imaging-OCT and OCT angiography were performed upon referral and
at subsequent follow-ups. RESULTS: Twenty-five eyes from 25 patients (9 women and
16 men, mean age of 63.4 years) were enrolled. The diagnoses of CSCR were already
established by the referring physicians in 10 patients, acute in 15% and chronic
in 26%; 48% of patients were referred with a diagnosis of type 1 CNV, and 11% of
CSCR complicated by CNV. After performing OCT angiography, 2 masked examiner
identified 7 type 1 CNV (29%), 18 eyes with pachychoroid disease of which 31%
pachychoroid pigment epitheliopathies (PPEs) at baseline evolved to CSCR, 22% PPE
at baseline evolved to pachychoroid neovasculopathy, 18% pachychoroid
neovasculopathy stable. CONCLUSION: Central serous chorioretinopathy, type 1 CNV,
and the pachychoroid spectrum of diseases cause abnormalities in the choroidal
circulation that make the overlying RPE dysfunctional, resulting in flat
irregular PED. Discrimination between avascular and vascular flat irregular PEDs
is crucial for a good visual outcome, but since chronic alterations of the RPE
can compromise the diagnostic specificity of FA and ICGA, OCT angiography may
become a fundamental tool to differentiate these clinical entities.
PMID- 28497337
TI - Identification of calmodulin binding proteins in the entomopathogenic fungus
Beauveria bassiana.
AB - Calmodulin (CaM) is a primary Ca2+ receptor and plays a pivotal role in a variety
of cellular responses in eukaryotes. Even though a large number of CaM-binding
proteins are well known in yeast, plants, and animals, little is known regarding
CaM-targeted proteins in filamentous fungi. To identify CaM-binding proteins in
filamentous fungi, we used a proteomics method coupled with co
immunoprecipitation (CoIP) and MALDI-TOF/TOF mass spectrometry (MS) in Beauveria
bassiana. Through this method, we identified ten CaM-binding proteins in B.
bassiana. One of the CaM-targeted proteins was the heat shock protein 70
(BbHSP70) in B. bassiana. Our biochemical study showed that ATP inhibits the
molecular interaction between BbHSP70 and CaM, suggesting a regulatory mechanism
between CaM and ATP for regulating BbHSP70.
PMID- 28497338
TI - Decreased Spontaneous Baroreflex Sensitivity as an Early Marker for Progression
of Haemorrhage.
AB - INTRODUCTION: Blood donation provides an ideal setup for assessment of
cardiovascular responses to mild hypovolemia for understanding the underlying
mechanisms. AIM: To evaluate cardiovascular responses in time and magnitude by
estimating the spontaneous baroreflex sensitivity (BRS) during and after donation
of 450 ml of blood. METHODS: Continuous beat-to-beat blood pressure and lead II
ECG was recorded before, during and after blood donation in 54 healthy volunteers
(age 34.7 +/- 5.08 years; weight 77.9 +/- 8.20 kg), followed by offline analyses
of baroreflex sensitivity. RESULTS: The systolic, diastolic or mean blood
pressures did not change during or after the blood donation. Decrease in pulse
pressure and increase in heart rate was observed post donation. The spontaneous
BRS decreased during [8.68 (6.038-12.69) ms/mmHg] and after blood donation [9.401
(6.396-11.59) ms/mmHg] as compared to the baseline [12.83 (6.884-18.18) ms/mmHg]
with a significant decrease in alpha-HF on spectral analysis. CONCLUSION: Mild
blood loss (450 ml) results in non-hypotensive haemorrhage with a decrease in
spontaneous BRS before the rise of heart rate during blood donation.
PMID- 28497339
TI - Follow-up of Antihypertensive Therapy Improves Blood Pressure Control: Results of
HYT (HYperTension survey) Follow-up.
AB - INTRODUCTION: Although improved during the past few years, blood pressure control
remains sub optimal. AIM: The impact of follow-up assessment on blood pressure
control was evaluated in a group of patients of the HYT (HYperTension survey),
treated with a combination of different dihydropyridine calcium-channel blockers
(CCBs regimen) and inhibitors of renin-angiotensin-aldosterone system (RAAS) and
with uncontrolled blood pressure. This was obtained assessing (a) the rate of
blood pressure control at 3 and 6 months of follow-up in the whole group of
patients, (b) the rate of blood pressure control and the average blood pressure
values in subjects treated with different DHP-CCBs regimen. METHODS: From the
4993 patients with uncontrolled blood pressure, (BP >= 140/90 or >=140/85 in
patients with diabetes), 3729 (mean age 61.2 +/- 11.5 years), maintained CCBs
regimen combined wih RAAS blockers and were evaluated at 3 and 6 months follow
up. At each visit BP (semiautomatic device, Omron-M6, 3 measurements), heart
rate, adverse events and treatment persistence were collected. RESULTS: At 1st
and 2nd follow-up the rate of controlled BP was 63.5 and 72.8% respectively (p <
0.05 vs 35.3% at baseline), whereas in diabetes was 32.5 and 37.9% respectively
(p < 0.05 vs 20% at baseline). No differences in heart rate were observed. No
differences in control rate were observed between the different CCBs regimen. The
incidence of drugs related adverse events was 3.6%. CONCLUSIONS: These findings
provide evidence that: (a) the follow-up of hypertensive patients under therapy
increase the rate of blood pressure control; (b) there is no significant
difference in the antihypertensive effect between different CCBs regimen;
PMID- 28497340
TI - Glycogen Shunt Activity and Glycolytic Supercompensation in Astrocytes May Be
Distinctly Mediated via the Muscle Form of Glycogen Phosphorylase.
AB - Glycogen is the main storage form of glucose in the brain. In contrast with
previous beliefs, brain glycogen has recently been shown to play important roles
in several brain functions. A fraction of metabolized glucose molecules are being
shunted through glycogen before reentering the glycolytic pathway, a phenomenon
known as the glycogen shunt. The significance of glycogen in astrocyte energetics
is underlined by high activity of the glycogen shunt and the finding that
inhibition of glycogen degradation, under some conditions leads to a
disproportional increase in glycolytic activity, so-called glycolytic
supercompensation. Glycogen phosphorylase, the key enzyme in glycogen
degradation, is expressed in two different isoforms in brain, the muscle and the
brain isoform. Recent studies have illustrated how these are differently
regulated. In the present study, we investigate the role of the two isoforms in
glycolytic supercompensation in cultured astrocytes with the expression of either
one of the isoforms silenced by siRNA knockdown. When reintroducing glucose to
glucose-starved astrocytes, glycolytic activity increased dramatically.
Interestingly, the increase was 30% higher in astrocytes not expressing the
muscle isoform of glycogen phosphorylase. Based on these results and previously
published data we couple the muscle isoform of glycogen phosphorylase to
glycolytic supercompensation and glycogen shunt activity, giving insights to the
underlying mechanistic of these phenomena.
PMID- 28497341
TI - Chronic TNFalpha Exposure Induces Robust Proliferation of Olfactory Ensheathing
Cells, but not Schwann Cells.
AB - TNFalpha is persistently elevated in many injury and disease conditions. Previous
reports of cytotoxicity of TNFalpha for oligodendrocytes and their progenitors
suggest that the poor endogenous remyelination in patients with traumatic injury
or multiple sclerosis may be due in part to persistent inflammation.
Understanding the effects of inflammatory cytokines on potential cell therapy
candidates is therefore important for evaluating the feasibility of their use. In
this study, we assessed the effects of long term exposure to TNFalpha on
viability, proliferation, migration and TNFalpha receptor expression of cultured
rat olfactory ensheathing cells (OECs) and Schwann cells (SCs). Although OECs and
SCs transplanted into the CNS produce similar myelinating phenotypes, and might
be expected to have similar therapeutic uses, we report that they have very
different sensitivities to TNFalpha. OECs exhibited positive proliferative
responses to TNFalpha over a much broader range of concentrations than SCs. Low
TNFalpha concentrations increased proliferation and migration of both OECs and
SCs, but SC number declined in the presence of 100 ng/ml or higher concentrations
of TNFalpha. In contrast, OECs exhibited enhanced proliferation even at high
TNFalpha concentrations (up to 1 ug/ml) and showed no evidence of TNF
cytotoxicity even at 4 weeks post-treatment. Furthermore, while both OECs and SCs
expressed TNFalphaR1 and TNFalphaR2, TNFalpha receptor levels were downregulated
in OECs after exposure to100 ng/ml TNFalpha for 5-7 days, but were either
elevated or unchanged in SCs. These results imply that OECs may be a more
suitable cell therapy candidate if transplanted into areas with persistent
inflammation.
PMID- 28497342
TI - Exploration of the Acetylcholinesterase Inhibitory Activity of Some Alkaloids
from Amaryllidaceae Family by Molecular Docking In Silico.
AB - Alzheimer's disease (AD) is a progressive condition, where dementia symptoms
gradually worsen. Biochemically the disease is characterized by the presence of
neuritic plaques, neurofibrillary tangles, in addition to cholinergic dysfunction
in the central nervous system. The role of the cholinergic neurotransmission in
AD is the basis of the widely accepted cholinergic hypothesis. Some of the most
relevant therapies for the treatment of the disease are based on the
acetylcholinesterase (AChE) inhibitor activity; however, these therapies are not
effective to stop the disease progression, but only can temporarily slow down the
worsening of dementia symptoms, and improve quality of life of patients and their
caregivers. In recent years, plant alkaloids extracted from Amaryllidaceae family
have received great attention due to the well-known anti cholinergic activity. In
this context, the purpose of this study was to apply the docking molecular in
silico analysis aiming to examine the recombinant human AChE enzyme (rhAChE)
inhibitory activity displayed by different alkaloids from Amaryllidaceae family.
Overall, the present results support the idea that alkaloids reported in this
research are capable of interacting with rhAChE-binding sites.
PMID- 28497343
TI - BDNF Contributes to Spinal Long-Term Potentiation and Mechanical Hypersensitivity
Via Fyn-Mediated Phosphorylation of NMDA Receptor GluN2B Subunit at Tyrosine 1472
in Rats Following Spinal Nerve Ligation.
AB - Previously we have demonstrated that brain-derived neurotrophic factor (BDNF)
contributes to spinal long-term potentiation (LTP) and pain hypersensitivity
through activation of GluN2B-containing N-methyl-D-aspartate (GluN2B-NMDA)
receptors in rats following spinal nerve ligation (SNL). However, the molecular
mechanisms by which BDNF impacts upon GluN2B-NMDA receptors and spinal LTP still
remain unclear. In this study, we first documented that Fyn kinase-mediated
phosphorylation of GluN2B subunit at tyrosine 1472 (pGluN2BY1472) was involved in
BDNF-induced spinal LTP and pain hypersensitivity in intact rats. Second, we
revealed a co-localization of Fyn and GluN2B-NMDA receptor in cultured dorsal
horn neurons, implying that Fyn is a possible intermediate kinase linking
BDNF/TrkB signaling with GluN2B-NMDA receptors in the spinal dorsal horn.
Furthermore, we discovered that both SNL surgery and intrathecal active Fyn could
induce an increased expression of dorsal horn pGluN2BY1472, as well as pain
hypersensitivity in response to von Frey filaments stimuli; and more importantly,
all these actions were effectively abrogated by pre-treatment with either PP2 or
ifenprodil to respectively inhibit Fyn kinase and GluN2B-NMDA receptors activity.
Moreover, we found that intrathecal administration of BDNF scavenger TrkB-Fc
prior to SNL surgery, could prevent the nerve injury-induced increase of both
pFynY420 and pGluN2BY1472 expression, and also inhibit the mechanical allodynia
in neuropathic rats. Collectively, these results suggest that Fyn kinase-mediated
pGluN2BY1472 is critical for BDNF-induced spinal LTP and pain hypersensitivity in
SNL rats. Therefore, the BDNF-Fyn-GluN2B signaling cascade in the spinal dorsal
horn may constitute a key mechanism underlying central sensitization and
neuropathic pain development after peripheral nerve injury.
PMID- 28497344
TI - Genipin Inhibits LPS-Induced Inflammatory Response in BV2 Microglial Cells.
AB - Genipin, an aglycon of geniposide, has been reported to have anti-inflammatory
effect. However, the anti-inflammatory activity of genipin on LPS-stimulated BV2
microglial cells has not been reported. In this study, we investigated the
molecular mechanisms responsible for the anti-inflammatory activity of genipin
both in vivo and in vitro. The levels of TNF-alpha, IL-1beta, NO and PGE2 were
detected by ELISA. The expression of Nrf2, HO-1, and NF-kappaB were detected by
western blot analysis. In vivo, genipin significantly attenuated LPS-induced
memory deficit in the Morris water maze and passive avoidance tasks. Genipin also
inhibited LPS-induced TNF-alpha and IL-1beta expression in brain tissues. In
vitro, our results showed that genipin inhibited LPS-induced TNF-alpha, IL-1beta,
NO and PGE2 production in a concentration-dependent manner. Genipin also
suppressed LPS-induced NF-kappaB activation. In addition, the expression of Nrf2
and HO-1 were up-regulated by treatment of genipin. Furthermore, the inhibition
of genipin on inflammatory mediator production was attenuated by transfection
with Nrf2 siRNA. In conclusion, genipin inhibited LPS-induced inflammatory
response by activating Nrf2 signaling pathway in BV2 microglia.
PMID- 28497345
TI - Retinol (Vitamin A) Increases alpha-Synuclein, beta-Amyloid Peptide, Tau
Phosphorylation and RAGE Content in Human SH-SY5Y Neuronal Cell Line.
AB - Retinoids (vitamin A and derivatives) are recognized as essential factors for
central nervous system (CNS) development. Retinol (vitamin A) also was postulated
to be a major antioxidant component of diet as it modulates reactive species (RS)
production and oxidative stress in biological systems. Oxidative stress plays a
major role either in pathogenesis or development of neurodegenerative diseases,
or even in both. Here we investigate the role of retinol supplementation to human
neuron-derived SH-SY5Y cells over RS production and biochemical markers
associated to neurodegenerative diseases expressed at neuronal level in
Parkinson's disease and Alzheimer's disease: alpha-synuclein, beta-amyloid
peptide, tau phosphorylation and RAGE. Retinol treatment (24 h) impaired cell
viability and increased intracellular RS production at the highest concentrations
(7 up to 20 uM). Antioxidant co-treatment (Trolox 100 uM) rescued cell viability
and inhibited RS production. Furthermore, retinol (10 uM) increased the levels of
alpha-synuclein, tau phosphorylation at Ser396, beta-amyloid peptide and RAGE. Co
treatment with antioxidant Trolox inhibited the increased in RAGE, but not the
effect of retinol on alpha-synuclein, tau phosphorylation and beta-amyloid
peptide accumulation. These data indicate that increased availability of retinol
to neurons at levels above the cellular physiological concentrations may induce
deleterious effects through diverse mechanisms, which include oxidative stress
but also include RS-independent modulation of proteins associated to progression
of neuronal cell death during the course of neurodegenerative diseases.
PMID- 28497347
TI - Nano Copper Induces Apoptosis in PK-15 Cells via a Mitochondria-Mediated Pathway.
AB - Nano-sized copper particles are widely used in various chemical, physical, and
biological fields. However, earlier studies have shown that nano copper particles
(40-100 MUg/mL) can induce cell toxicity and apoptosis. Therefore, this study was
conducted to investigate the role of nano copper in mitochondrion-mediated
apoptosis in PK-15 cells. The cells were treated with different doses of nano
copper (20, 40, 60, and 80 MUg/mL) to determine the effects of apoptosis using
acridine orange/ethidium bromide (AO/EB) fluorescence staining and a flow
cytometry assay. The levels of malondialdehyde (MDA) and superoxide dismutase
(SOD) in the PK-15 cells were examined using commercially available kits.
Moreover, the mRNA levels of the Bax, Bid, Caspase-3, and CYCS genes were
assessed by real-time PCR. The results revealed that nano copper exposure induced
apoptosis and changed the mitochondrial membrane potential. In addition, nano
copper significantly altered the levels of the Bax, Bid, Caspase-3, and CYCS
genes at a concentration of 40 MUg/mL. To summarize, nano copper significantly (P
< 0.05) decreased the level of SOD and increased the level of MDA in PK-15 cells.
Altogether, these results suggest that nano copper can play an important role in
inducing the apoptotic pathway in PK-15 cells, which may be the mechanism by
which nano copper induces nephrotoxicity.
PMID- 28497346
TI - Enhanced Autophagy Contributes to Protective Effects of GM1 Ganglioside Against
Abeta1-42-Induced Neurotoxicity and Cognitive Deficits.
AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder. The
aggregation of Abeta peptides, Abeta1-42 in particular, is thought to be a
fundamental pathogenic mechanism leading to the neuronal damage in AD. Recently,
monosialoganglioside GM1 is reported to possess pivotal neuroprotection in
neurodegenerative diseases. Previous studies have focused on the conformational
dynamics and the biochemical interaction of the amyloid-peptide with the GM1
ganglioside, as well as the protective effect of GM1 on cognition. However, the
phenomenon of autophagy with regard to neuronal dysfunction in AD is less
investigated. In the present study, GM1 treatment were investigated in an AD
mouse model and cultured PC12 dells to examine cognition-protective and
neuroprotective effects of GM1. Furthermore, GM1 was found to induce autophagy
via testing light chain 3 (LC3), Beclin1, neighbor of BRCA1 gene 1 protein and
p62 (a substrate of LC3). Chloroquine, an inhibitor of lysosomal, was used to
exclude the interference of lysosome, which could fuse with autophagosome and
then clear it. In the presence of the inhibitor of autophagy (3-methyladenine; 3
MA), the protective effect of GM1 on PC12 cells in Abeta (1-42) induced toxic
conditions was diminished. Interestingly, the expression of histone deacetylase 1
was increased in PC12 cells when treated with GM1, indicating that autophagy
might be activated by GM1 through a pathway integrates protein acetylation. This
study provides a novel insight into the protective role of GM1 against Abeta (1
42)-induced neurotoxicity via enhancing autophagy.
PMID- 28497348
TI - Evaluation of Dietary Palygorskite Supplementation on Growth Performance, Mineral
Accumulations, Antioxidant Capacities, and Meat Quality of Broilers Fed Lead
Contaminated Diet.
AB - The objective of this study was to evaluate influence of dietary palygorskite
(Pal) supplementation on growth performance, mineral accumulations in the tissues
(livers, kidneys, and muscles), antioxidant capacities, and meat quality of
broilers fed lead (Pb)-contaminated diet. One-hundred forty-four male broiler
chicks were randomly divided into three treatment groups, receiving a corn
soybean meal basal diet (the control group), the basal diet contaminated with 10
mg/kg Pb (the Pb group), and the basal diet with 10-g/kg Pal supplementation and
10-mg/kg Pb contamination (the Pal/Pb group) from 1 to 42 days of age,
respectively. Treatments did not affect growth performance of broilers in the 42
day study (P > 0.05). Compared with the control group, Pb contamination increased
Pb accumulation in the livers, kidneys, and muscles (P < 0.05); elevated
malondialdehyde accumulation in the livers, kidneys, and breast muscles;
glutathione peroxidase activity in the livers and superoxide dismutase activity
in the kidneys (P < 0.05); exacerbated drip loss in the pectoralis muscles (P <
0.05); and reduced glutathione peroxidase activity in the pectoralis muscles (P <
0.05) of broilers at 42 days of age. The values of these parameters were reversed
in the Pal/Pb group to levels comparable with those in the control group (P <
0.05). Additionally, Pal supplementation reduced redness value in the pectoralis
muscles (P < 0.05), and decreased Cu concentration in the pectoralis muscles and
livers at 42 days of age as well as its accumulation in the kidneys at both 21
and 42 days of age compared with the other two groups (P < 0.05). The results
suggested that dietary Pal supplementation would decrease Pb residue in the
tissues, alleviate oxidative stress, and affect meat quality of broilers exposed
to Pb.
PMID- 28497349
TI - SUV navigator enables rapid [18F]-FDG PET/CT image interpretation compared with
2D ROI and 3D VOI evaluations.
AB - PURPOSE: Positron emission tomography (PET) and the maximum standardized uptake
value (SUVmax) is a useful technique for assessing malignant tumors. Measurements
of SUVmax in multiple lesions per patient frequently require many time-consuming
procedures. To address this issue, we designed a novel interface named SUV
Navigator (SUVnavi), and the purpose of this study was to investigate its
utility. MATERIALS AND METHODS: We measured SUVmax in 661 lesions from 100
patients with malignant tumors. Diagnoses and SUVmax measurements were made with
SUVnavi, 2D, and 3D measurements. SUV measurement accuracy in each method were
also evaluated. RESULTS: The average reduction in time with SUVnavi versus 2D was
53.8% and 3D was 37.5%; time required with SUVnavi was significantly shorter than
with 2D and 3D (P < 0.001 and P < 0.001, respectively). The time reduction and
lesion number had a positive correlation (P < 0.001 and P < 0.001, respectively).
SUVmax agreed with precise SUVmax in all lesions measured with SUVnavi and 3D but
in only 466 of 661 lesions (70.5%) measured with 2D. CONCLUSION: SUVnavi may be
useful for rapid [18F]-fluorodeoxyglucose positron emission tomography/computed
tomography ([18F]-FDG PET/CT) image interpretation without reducing the accuracy
of SUVmax measurement.
PMID- 28497351
TI - Comment on "Epigenetics in the pathogenesis of RA".
PMID- 28497350
TI - Synovial cellular and molecular markers in rheumatoid arthritis.
AB - The profound alterations in the structure, cellular composition, and function of
synovial tissue in rheumatoid arthritis (RA) are the basis for the persistent
inflammation and cumulative joint destruction that are hallmarks of this disease.
In RA, the synovium develops characteristics of a tertiary lymphoid organ, with
extensive infiltration of lymphocytes and myeloid cells. Concurrently, the
fibroblast-like synoviocytes undergo massive hyperplasia and acquire a tissue
invasive phenotype. In this review, we summarize key components of these
processes, focusing on recently-described roles of selected molecular markers of
these cellular components of RA synovitis.
PMID- 28497352
TI - Monogenic Periodic Fever Syndromes: Treatment Options for the Pediatric Patient.
AB - Autoinflammatory diseases are disorders of the innate immune system characterized
by uncontrolled inflammation. The most commonly encountered autoinflammatory
diseases are the hereditary periodic fever syndromes, which present with fever
and other features of the skin, serosal membranes, and musculoskeletal system.
The main inherited (monogenic) periodic fever syndromes are familial
Mediterranean fever (FMF), cryopyrin-associated periodic syndrome (CAPS), tumor
necrosis factor receptor-associated periodic syndrome (TRAPS), and
hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD). Recent
advances in our understanding of the molecular and pathophysiological basis of
autoinflammatory diseases have provided new treatment strategies. Patients with
periodic fever syndromes have clearly benefited from anti-interleukin (IL)-1
treatment. Colchicine is still the mainstay of FMF therapy, but IL-1 blockade is
also effective if colchicine fails. Early diagnosis and effective treatment can
prevent irreversible organ damage. The scope of pathogenic mutations and more
targeted therapy for better management of these rare diseases remains to be
defined.
PMID- 28497354
TI - Farmer-suicide in India: debating the role of biotechnology.
AB - Indian Biotech opponents have attributed the increase of suicides to the
monopolization of GM seeds, centering on patent control, application of
terminator technology, marketing strategy, and increased production costs. The
contentions of the biotech opponents, however, have been criticized for a lack of
transparency in their modus operandi i.e. the use of methodology in their
argumentation. The fact is, however, that with the intention of getting the
attention of those capable of determining the future of GM cotton in India,
opponents resorted to generating controversies. Therefore, this article will
review and evaluate the multifaceted contentions of both opponents and defenders.
Although the association between seed monopolization and farmer-suicide is
debatable, we will show that there is a link between the economic factors
associated with Bt. cultivation and farmer suicide. The underlying thesis of
biotech opponents becomes all the more significant when analysed vis-a-vis the
contention of the globalization critics that there has been a political and
economic marginalization of the Indian farmers. Their accusation assumes
significance in the context of a fragile democracy like India where market forces
are accorded precedence over farmers' needs until election time.
PMID- 28497355
TI - The Generation of Dehydroalanine Residues in Protonated Polypeptides: Ion/Ion
Reactions for Introducing Selective Cleavages.
AB - We examine a gas-phase approach for converting a subset of amino acid residues in
polypeptide cations to dehydroalanine (Dha). Subsequent activation of the
modified polypeptide ions gives rise to specific cleavage N-terminal to the Dha
residue. This process allows for the incorporation of selective cleavages in the
structural characterization of polypeptide ions. An ion/ion reaction within the
mass spectrometer between a multiply protonated polypeptide and the sulfate
radical anion introduces a radical site into the multiply protonated polypeptide
reactant. Subsequent collisional activation of the polypeptide radical cation
gives rise to radical side chain loss from one of several particular amino acid
side chains (e.g., leucine, asparagine, lysine, glutamine, and glutamic acid) to
yield a Dha residue. The Dha residues facilitate preferential backbone cleavages
to produce signature c- and z-ions, demonstrated with cations derived from
melittin, mechano growth factor (MGF), and ubiquitin. The efficiencies for
radical side chain loss and for subsequent generation of specific c- and z-ions
have been examined as functions of precursor ion charge state and activation
conditions using cations of ubiquitin as a model for a small protein. It is noted
that these efficiencies are not strongly dependent on ion trap collisional
activation conditions but are sensitive to precursor ion charge state. Moderate
to low charge states show the greatest overall yields for the specific Dha
cleavages, whereas small molecule losses (e.g., water/ammonia) dominate at the
lowest charge states and proton catalyzed amide bond cleavages that give rise to
b- and y-ions tend to dominate at high charge states. Graphical Abstract ?.
PMID- 28497356
TI - N3 and O2 Protonated Conformers of the Cytosine Mononucleotides Coexist in the
Gas Phase.
AB - The gas-phase conformations of the protonated forms of the DNA and RNA cytosine
mononucleotides, [pdCyd+H]+ and [pCyd+H]+, are examined by infrared multiple
photon dissociation (IRMPD) action spectroscopy over the IR fingerprint and
hydrogen-stretching regions complemented by electronic structure calculations.
The low-energy conformations of [pdCyd+H]+ and [pCyd+H]+ and their relative
stabilities are computed at the B3LYP/6-311+G(2d,2p)//B3LYP/6-311+G(d,p) and
MP2(full)/6-311+G(2d,2p)//B3LYP/6-311+G(d,p) levels of theory. Comparisons of the
measured IRMPD action spectra and B3LYP/6-311+G(d,p) linear IR spectra computed
for the low-energy conformers allow the conformers present in the experiments to
be determined. Similar to that found in previous IRMPD action spectroscopy
studies of the protonated forms of the cytosine nucleosides, [dCyd+H]+ and
[Cyd+H]+, both N3 and O2 protonated cytosine mononucleotides exhibiting an anti
orientation of cytosine are found to coexist in the experimental population. The
2'-hydroxyl substituent does not significantly influence the most stable
conformations of [pCyd+H]+ versus those of [pdCyd+H]+, as the IRMPD spectral
profiles of [pdCyd+H]+ and [pCyd+H]+ are similar. However, the presence of the 2'
hydroxyl substituent does influence the relative intensities of the measured
IRMPD bands. Comparisons to IRMPD spectroscopy studies of the deprotonated forms
of the cytosine mononucleotides, [pdCyd-H]- and [pCyd-H]-, provide insight into
the effects of protonation versus deprotonation on the conformational features of
the nucleobase and sugar moieties. Likewise, comparisons to results of IRMPD
spectroscopy studies of the protonated cytosine nucleosides provide insight into
the influence of the phosphate moiety on structure. Comparison with previous ion
mobility results shows the superiority of IRMPD spectroscopy for distinguishing
various protonation sites. Graphical Abstract ?.
PMID- 28497357
TI - Socioeconomic inequalities in treatment of individuals with common mental
disorders regarding subsequent development of mental illness.
AB - PURPOSE: Socioeconomic differences appear to be reflected in both, the
development and the treatment of common mental disorders (CMDs, i.e. depressive,
anxiety and stress-related disorders). Underlying mechanisms of these
inequalities are to date not fully understood. This study aimed to investigate if
(1) there are socioeconomic differences with regard to type of treatment and (2)
if the socioeconomic status modifies the association between treatment and
subsequent inpatient care or suicide attempt, respectively, in individuals with
CMDs. METHODS: The study population comprised 66,097 individuals aged 18-59 on
sick-leave due to a CMD during 2006 in Sweden. Cox regression with a follow-up
from 2007 through 2010 estimated crude and multivariate hazard ratios (HR) with
95% confidence intervals (CI). RESULTS: Individuals with sickness absence due to
CMDs and a higher educational level were had a lower proportions of specialised
health care and combined psychiatric medication than their counterparts with
lower education. However, if high educated CMD patients received more combined
medication, associations with subsequent mental inpatient care (p < 0.01) and
suicide attempt (p < 0.05) were stronger than for their counterparts with low
education. Moreover, previous inpatient care due to mental disorders was
associated with higher HRs of subsequent suicide attempt in CMD patients with
high education (HR 5.88; CI 3.02-11.45) compared to those with low education
(1.96; 1.06-3.60). CONCLUSION: Findings suggest that socioeconomic inequalities
shape differences in treatment measures and mental health development in
individuals with CMDs. These differences might signal discrepancies in treatment
per se or reflect morbidity differences requiring different treatment regimens,
or may be due to the fact that different diagnoses are given in different
educational strata due to differential role of stigma.
PMID- 28497358
TI - Predictive value of selected biomarkers related to metabolism and oxidative
stress in children with autism spectrum disorder.
AB - Autism spectrum disorder (ASD) as a neurodevelopmental disorder is characterized
by impairments in social interaction, communication, and restricted, repetitive
behavior. Several and reproducible studies have suggested that oxidative stress
may represent one of the primary etiological mechanism of ASD that can be
targeted for therapeutic intervention. In the present study, multiple regression
and combined receiver operating characteristic (ROC) analysis were used to search
for a relationship between impaired energy and oxidative metabolic pathways in
the etiology of ASD and to find the linear combination that maximizes the partial
area under a ROC curve for a pre-identified set of markers related to energy
metabolism and oxidative stress. Thirty children with ASD and 30 age and gender
matched controls were enrolled in the study. Using either spectrophotometric or
ELISA-colorimetric assay, levels of lipid peroxides, vitamin E, vitamin C,
glutathione (GSH)/glutathione disulfide (GSSG) together with the enzymatic
activity of catalase, plasma glutathione peroxidase (GPx), and blood superoxide
dismutase (SOD), were measured in peripheral blood samples, as biomarkers related
to oxidative stress. Creatine kinase, ectonucleotidases (ADPase and ATPase)
Na+/K+ (ATPase), lactate, inorganic phosphate, and levels of adenosine
monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate
(ATP) together with adenylate energy charge, were also measured as markers of
impaired energy metabolism. Statistical analysis using ROC curves, multiple and
logistic regression were performed. A remarkable increase in the area under the
curve for most of the combined markers, representing both energy impaired
metabolism or oxidative stress, was observed by using combined ROC analyses.
Moreover, higher specificity and sensitivity of the combined markers were also
reported. The present study indicated that the measurement of the predictive
value of selected biomarkers related to energy metabolism and oxidative stress in
children with ASD using ROC analysis should lead to the better identification of
the etiological mechanism of ASD associated with metabolism and diet. Agents with
activity against the impaired metabolic pathway associated with ASD including the
metabolic defects and involved enzymes hold a promise as a novel therapy for ASD.
PMID- 28497359
TI - The pattern of thalamocortical and brain stem projections to the vibrissae
related sensory and motor cortices in de-whiskered congenital hypothyroid rats.
AB - The present study is designed to investigate the plastic organization of the
thalamo-cortical (TC) and brain stem afferents of whisker primary sensory (wS1)
and motor (wM1) cortical areas in congenital hypothyroid (CH) pups following
whisker deprivation (WD) from neonatal to adolescence period. Maternal
hypothyroidism was induced by adding propylthiouracil (PTU) to the drinking water
from early embryonic day 16 to postnatal day (PND) 60. Pregnant rats were divided
into intact and CH groups (n = 8). In each group, the total whiskers of pups (4
of 8) were trimmed continuously from PND 1 to PND 60. Retrograde tracing
technique with WGA-HRP was performed in the present study. Retrogradely labeled
neurons were observed in the specific thalamic nuclei (VPM and VL) following
separately WGA-HRP injections into wS1/M1 cortical areas. The number of labeled
cells in the VPM, VL, VM and PO nuclei of the thalamus significantly decreased in
CH offsprings rats (P < 0.05). Neonatal WD did not show any significant effects
on the number of VPM, VL, VM and PO labeled projection neurons to wS1 and wM1
cortical areas. In addition, retrogradely labeled neurons in dorsal raphe (DR)
and locus coeruleus (LC) nuclei were observed in all experimental groups. The
number of DR and LC labeled neurons were higher in the CH and whisker deprived
groups compared to their matching controls (P < 0.05). Upon our results, CH and
WD had no synergic or additive effects on the TC and brain stem afferent patterns
of barrel sensory and motor cortices.
PMID- 28497360
TI - Neuroprotective effects of Nigella sativa extract upon the hippocampus in PTU
induced hypothyroidism juvenile rats: A stereological study.
AB - This study aimed to examine the neuroprotective effects of Nigella sativa (N.
sativa) in the hippocampus of propylthiouracil (PTU)-induced hypothyroid rats
during neonatal and juvenile growth. Twenty- five pregnant rats from early
gestation (GD 0) were divided into five groups: (1) control (received drinking
water), (2) PTU (received 0.005% PTU in drinking water), (3-5) PTU + NS 0.05%,
PTU + NS 0.1%, PTU + NS 0.2% (along with PTU, received 0.05%, 0.1% and 0.2% W/V
of N. sativa respectively) and treatment continued until postnatal day 60 (PN
60). The brains of male pups were removed for histological and stereological
assessments. N. sativa extract significantly reduced the production of dark
neurons and apoptotic cells in different areas of the hippocampus compared to the
PTU group. Moreover, it significantly attenuated the effect of hypothyroidism on
the volume reduction of the hippocampus. The results of the present study
suggested that N. sativa extract has a potential ability to prevent the
hippocampal neural damage after inducing hypothyroidism during neonatal and
juvenile growth in rats.
PMID- 28497361
TI - Design and characterization of lisinopril-loaded superparamagnetic nanoparticles
as a new contrast agent for in vitro, in vivo MRI imaging, diagnose the tumors
and drug delivery system.
AB - Superparamagnetic gamma-Fe2O3@SiO2@lisinopril (MNPs-Lisinopril) nanoparticles are
T2 and T2* negative contrast agents for magnetic resonance imaging. In this work,
we report the preparation of lisinopril-coated MNPs for the first time as new T2
and T2* negative contrast agent for in vitro and in vivo MRI imaging and
demonstrate the potential it simultaneously for drug delivery system, diagnose
the tumors and MRI contrast agent. Measurements on the relaxivities (r1, r2 and
r2*) of the MNPs-Lisinopril were determined in deionized water (in vitro).
Furthermore, after subcutaneous injection of the MNPs-Lisinopril into 4T1
(ATCC(r) CRL2539TM) tumor in BALB/c mice, the relaxivities were determined by a
1.5 T MRI apparatus (in vivo). T2- and T2*-weighted MRI images of MNPs-Lisinopril
showed that the MR signal intensity decreased significantly with increasing
nanoparticle concentration in water. With measured r2 values up to 236.66 mM-1s
1, our MNPs-Lisinopril show better performance than commercial alternatives. Also
we tested drug release of Lisinopril coated MNPs at two different pHs. The MNPs-
Lisinopril is a pH-sensitive drug delivery system and releases different amounts
of lisinopril from MNPs-Captopril in different pHs.
PMID- 28497362
TI - Size and shape-dependent cytotoxicity profile of gold nanoparticles for
biomedical applications.
AB - Metallic nanoparticles, in particular gold nanoparticles (AuNPs), offer a wide
spectrum of applications in biomedicine. A crucial issue is their cytotoxicity,
which depends greatly on various factors, including morphology of nanoparticles.
Because metallic nanoparticles have an effect on cell membrane integrity, their
shape and size may affect the viability of cells, due to their different
geometries as well as physical and chemical interactions with cell membranes.
Variations in the size and shape of gold nanoparticles may indicate particular
nanoparticle morphologies that provide strong cytotoxicity effects. Synthesis of
different sized and shaped bare AuNPs was performed with spherical (~ 10 nm),
nanoflowers (~ 370 nm), nanorods (~ 41 nm), nanoprisms (~ 160 nm) and nanostars
(~ 240 nm) morphologies. These nanostructures were characterized and interacting
with cancer (HeLa) and normal (HEK293T) cell lines and cell viability tests were
performed by WST-1 tests and fluorescent live/dead cell imaging experiments. It
was shown that various shapes and sizes of gold nanostructures may affect the
viability of the cells. Gold nanospheres and nanorods proved to be more toxic
than star, flower and prism gold nanostructures. This may be attributed to their
small size and aggregation process. This is the first report concerning a
comparison of cytotoxic profile in vitro with a wide spectrum of bare AuNPs
morphology. The findings show their possible use in biomedical applications.
PMID- 28497363
TI - Spatial Updating Strategy Affects the Reference Frame in Path Integration.
AB - This study investigated how spatial updating strategies affected the selection of
reference frames in path integration. Participants walked an outbound path
consisting of three successive waypoints in a featureless environment and then
pointed to the first waypoint. We manipulated the alignment of participants'
final heading at the end of the outbound path with their initial heading to
examine the adopted reference frame. We assumed that the initial heading defined
the principal reference direction in an allocentric reference frame. In
Experiment 1, participants were instructed to use a configural updating strategy
and to monitor the shape of the outbound path while they walked it. Pointing
performance was best when the final heading was aligned with the initial heading,
indicating the use of an allocentric reference frame. In Experiment 2,
participants were instructed to use a continuous updating strategy and to keep
track of the location of the first waypoint while walking the outbound path.
Pointing performance was equivalent regardless of the alignment between the final
and the initial headings, indicating the use of an egocentric reference frame.
These results confirmed that people could employ different spatial updating
strategies in path integration (Wiener, Berthoz, & Wolbers Experimental Brain
Research 208(1) 61-71, 2011), and suggested that these strategies could affect
the selection of the reference frame for path integration.
PMID- 28497364
TI - Concreteness and abstraction in everyday explanation.
AB - A number of philosophers argue for the value of abstraction in explanation.
According to these prescriptive theories, an explanation becomes superior when it
leaves out details that make no difference to the occurrence of the event one is
trying to explain (the explanandum). Abstract explanations are not frugal
placeholders for improved, detailed future explanations but are more valuable
than their concrete counterparts because they highlight the factors that do the
causal work, the factors in the absence of which the explanandum would not occur.
We present several experiments that test whether people follow this prescription
(i.e., whether people prefer explanations with abstract difference makers over
explanations with concrete details and explanations that omit descriptively
accurate but causally irrelevant information). Contrary to the prescription, we
found a preference for concreteness and detail. Participants rated explanations
with concrete details higher than their abstract counterparts and in many cases
they did not penalize the presence of causally irrelevant details. Nevertheless,
causality still constrained participants' preferences: They downgraded concrete
explanations that did not communicate the critical causal properties.
PMID- 28497365
TI - Clinical utility of soluble interleukin-2 receptor in hemophagocytic syndromes: a
systematic scoping review.
AB - The serum-soluble interleukin-2 receptor (sIL-2r) level is considered an
important diagnostic test and disease marker in hemophagocytic
syndromes/hemophagocytic lymphohistiocytosis (HPS/HLH). However, this cytokine
receptor is rarely measured in clinical practice and has been excluded from
recent diagnostic/classification criteria such as the HScore and macrophage
activation syndrome (MAS) 16. We performed a systematic scoping review of 64
articles (1975-2016) examining the clinical utility of sIL-2r in HPS/HLH. Twenty
two articles describe sIL-2r as a sensitive diagnostic marker for HLH, but only
three distinct datasets actually address sensitivity. The original HLH-2004
Guidelines reported sensitivity of 93% and specificity of 100% for sIL-2r >=
2400, based on a pediatric dataset (n = 152) which is published for the first
time in this review. Two pediatric studies reported sensitivity of 89% for sIL-2r
>= 2400 in diagnosis of MAS complicating juvenile idiopathic arthritis (JIA) (n =
27) and 88% for secondary HLH in acute liver failure (n = 9). Twenty articles
described sIL-2r as a dynamic marker of disease activity that falls with response
to treatment, and 15 described high initial sIL-2r levels >10,000 U/mL as a poor
prognostic marker. The ability of sIL-2r to distinguish between subtypes of
HPS/HLH was inconsistent. This review confirms the importance of soluble IL-2r as
a diagnostic and disease marker in HPS/HLH, but also reveals the need for more
primary data about its performance characteristics, particularly in adults. More
emphasis should be made in including this simple, inexpensive test in clinical
practice and studies of HPS/HLH.
PMID- 28497366
TI - Evaluation of persistence and distribution of intra-dermally administered PKH26
labelled goat bone marrow derived mesenchymal stem cells in cutaneous wound
healing model.
AB - The current study was designed to study the persistence and distribution of
caprine bone marrow derived mesenchymal stem cells (cBM-MSCs) when administered
intra-dermally in experimentally induced cutaneous wounds in rabbits. MSC's from
goat bone marrow were isolated and their differentiation potential towards
adipogenic and osteogenic lineages were assayed in vitro. The isolated cells were
phenotypically analysed using flow cytometry for the expression of MSC specific
matrix receptors (CD73, CD105 and Stro-1) and absence of hematopoietic lineage
markers. Further, these in vitro expanded MSCs were stained with PKH26 lipophilic
cell membrane red fluorescent dye and prepared for transplantation into cutaneous
wounds created on rabbits. Five, 2 cm linear full thickness skin incisions were
created on either side of dorsal midline of New Zealand white rabbits (n = 4).
Four wounds in each animal were implanted intra-dermally with PKH26 labelled cBM
MSCs suspended in 500 ul of Phosphate Buffer Saline (PBS). Fifth wound was
injected with PBS alone and treated as negative control. The skin samples were
collected from respective wounds on 3, 7, 10 and 14 days after the wound
creation, and cryosections of 6 uM were made from it. Fluorescent microscopy of
these cryosections showed that the PKH26 labelled transplanted cells and their
daughter cells demonstrated a diffuse pattern of distribution initially and were
later concentrated towards the wound edges and finally appeared to be engrafted
with the newly developed skin tissues. The labelled cells were found retained in
the wound bed throughout the period of 14 days of experimental study with a
gradual decline in their intensity of red fluorescence probably due to the dye
dilution as a result of multiple cell division. The retention of transplanted
MSCs within the wound bed even after the complete wound healing suggests that in
addition to their paracrine actions as already been reported, they may have
direct involvement in various stages of intricate wound healing process which
needs to be explored further.
PMID- 28497367
TI - ENPP1 121Q functional variant enhances susceptibility to coronary artery disease
in South Indian patients with type 2 diabetes mellitus.
AB - Insulin resistance is associated with endothelial dysfunction and ensuing
cardiovascular diseases in type 2 diabetes mellitus (T2DM) patients. ENPP1 is a
key modulator of insulin signaling and its polymorphism, K121Q, increases the
potency to competitively inhibit insulin receptor binding. We investigated the
association of ENPP1 121Q variant with coronary artery disease (CAD) in patients
with and without T2DM in South Indian population. Our study was conducted in 913
subjects: 198 patients with CAD, 284 patients in whom T2DM and CAD co-exists, 160
patients with T2DM and no CAD history, and 271 healthy volunteers. Genotyping was
performed using PCR-RFLP and PCR-DNA sequencing. Genotype frequency of ENPP1 121Q
was higher in disease groups compared to healthy subjects (p < 0.05). T2DM
patients who carried polymorphic AC/CC genotypes were at 12.8-fold enhanced risk
to CAD (95% CI 4.97-37.18, p < 0.01). Moreover we observed that 121Q, both in
heterozygous and homozygous polymorphic states, was a risk factor for CAD without
diabetes (OR 4.15, p < 0.01). 121Q variant was associated with T2DM patients with
no CAD history too, but the risk was statistically insignificant after
multivariate logistic regression analysis (OR 2.32, p > 0.05). We conclude that
ENPP1 121Q variant is associated with increased risk for CAD in patients with
T2DM in South Indian population. We also report that 121Q variant of ENPP1 was an
independent risk factor for CAD irrespective of diabetic milieu. Factors which
enhance insulin resistance increase the risk for onset and progression of
coronary atherosclerosis irrespective of a diabetic background.
PMID- 28497368
TI - Honeydew honey: biological effects on skin cells.
AB - Honey is a natural product well known by humankind and now reconsidered for its
use as topical agent for wound and burn treatments. Floral honey is made by
honeybees from the nectar of blossoms, while honeydew honey is prepared from
secretions of plants or excretions of plant-sucking insects. Chemical composition
is different between blossom and honeydew honeys and there is very few
information about the biological properties of honeydew honey. So, this study was
specifically designed to explore the potential wound healing effects of the
honeydew honey. We used in vitro scratch wound healing model consisting of
fibroblasts and keratinocytes. Data showed that honeydew honeys is able to
increase wound closure by acting both on fibroblasts and keratinocytes. Based on
our findings, honeydew honey has the potential to be useful for clinical
settings.
PMID- 28497369
TI - Co-enzyme Q10 and acetyl salicylic acid enhance Hsp70 expression in primary
chicken myocardial cells to protect the cells during heat stress.
AB - We investigated the effects of co-enzyme Q10 (Q10) and acetyl salicylic acid
(ASA) on expression of Hsp70 in the protection of primary chicken myocardial
cells during heat stress. Western blot analysis showed that Q10 and ASA
accelerated the induction of Hsp70 when chicken myocardial cells were exposed to
hyperthermia. In the absence of heat stress, however, neither Q10 nor ASA are
able to upregulate Hsp70 expression. Analysis of enzymes that respond to cellular
damage and pathological examination revealed that ectopic expression of ASA and
Q10 alleviate cellular damage during heat stress. Quantification of heat shock
factors (HSF) indicated that treatment of ASA increased the expression of HSF-1
and HSF-3 during heat stress. Treatment with Q10 resulted in the elevation of HSF
1 expression. Expression of HSF-2 and HSF-4 was not affected by ASA or Q10.
Subcellular distribution analysis of HSF-1 and HSF-3 showed that in response to
heat stress ASA promoted nuclear translocation of HSF-1 and HSF-3, while Q10
promoted only HSF-1 nuclear translocation. Chromatin immunoprecipitation (ChIP)
analysis indicated that HSF-1 occupies the Hsp70 promoter in chicken primary
myocardial cells during heat stress and under normal conditions, while HSF-3
occupies the Hsp70 promoter only during heat stress. Real-time PCR analysis
revealed that ASA induces HSF-1 and HSF-3 binding to Hsp70 HSE, while Q10 only
induces HSF1 binding to Hsp70 HSE, in agreement with the impact of HSF1 and HSF3
silencing on Hsp70 expression. These data demonstrate that ASA and Q10 both
induce the expression of Hsp70 to protect chicken primary myocardial cells during
heat stress, but through distinct pathways.
PMID- 28497370
TI - IGF2BP1: a novel binding protein of p38 MAPK.
AB - Signal transduction pathways control various biological processes in cells
leading to distinct cellular functions. Protein-protein interactions and post
translational modifications are the physiological events that occur in signaling
pathway. p38 MAPK are known to be involved in regulating wide range of cellular
processes by interacting and activating relevant signaling molecules by means of
phosphorylation. Deregulation of p38 MAPK is associated with various pathological
conditions. In order to get an insight into the role played by p38 MAPK in
cellular signaling, studies were carried out to identify proteins that interact
with p38 MAPK. Mass spectrometry was used to identify the proteins present in p38
MAPK complex obtained by co-immunoprecipitation. Based on mass spectrometry data,
here we report insulin-like growth factor-II binding protein 1 (IGF2BP1) as a
novel interacting partner of p38 MAPK. IGF2BP1 is a RNA-binding protein
predominantly known to be involved in tumor progression. To reconfirm the mass
spectrometry data, in silico analysis was carried out. Based on different models
predicted in silico, we report the possible interaction domains of p38MAPK and
IGF2BP1. Considering the involvement of p38MAPK and IGF2BP1 in cancer, our study
opens up the possibility of p38MAPK regulating IGF2BP1 function, and the
possibility of targeting this novel interaction for developing cancer-treating
drugs is discussed.
PMID- 28497371
TI - Sestrin 2 attenuates neonatal rat cardiomyocyte hypertrophy induced by
phenylephrine via inhibiting ERK1/2.
AB - Cardiac hypertrophy is an adaptive response triggered by many physiological and
pathological conditions and will lead to heart failure eventually. Sestrin 2,
which is a stress-responsive protein, was reported to protect heart from ischemia
reperfusion injury. However, the role of Sestrin 2 in cardiac hypertrophy remains
unknown. In our present study, we aimed to explore the effects of Sestrin 2 on
cardiomyocyte hypertrophy. We found that knockdown of Sestrin 2 protein
aggravated cardiomyocyte hypertrophy induced by phenylephrine (PE), featured by
increased hypertrophic marker ANP and cell surface area. During this process,
ERK1/2 cascade was further activated, while p38, JNK1/2, and mTOR signaling
pathways were not affected by downregulation of Sestrin 2. Moreover,
overexpression of Sestrin 2 protein protected cardiomyocytes from PE-induced
hypertrophy and ERK1/2 cascade was suppressed correspondingly. Importantly,
pharmacological inhibition of ERK1/2 eliminated the exacerbated hypertrophic
phenotype due to Sestrin 2 protein knockdown. In conclusion, we discovered that
Sestrin 2 protected against cardiomyocyte hypertrophy induced by PE via
inhibiting ERK1/2 signaling.
PMID- 28497372
TI - SCARA5 plays a critical role in the progression and metastasis of breast cancer
by inactivating the ERK1/2, STAT3, and AKT signaling pathways.
AB - Scavenger receptor class A member 5 (SCARA5) is a candidate anti-oncogene in
several malignancies. However, whether SCARA5 is a suppressor gene in breast
cancer and its role in breast cancer cell growth and metastasis remain to be
determined. Here, we investigated the biological functions of SCARA5 in the
progression and metastasis of breast cancer and explored the underlying
mechanisms. A total of 65 breast cancer patients and three cell lines (ZR-75-30,
MCF-7, and MDA-MB-231) were analyzed in the study. RT-qPCR, western blotting, and
immunohistochemistry were used to detect mRNA and protein expression, and
lymphatic vessel density (LVD) and microvessel density (MVD). MTT, colony
formation, TUNEL assays, invasion assays and Transwell assays, and flow
cytometric analyses were used to evaluate the effect of SCARA5 on breast cancer
cells. SCARA5 was significantly downregulated in breast cancer tissues and cells
and significantly correlated with tumor size, histological grade, lymph node
metastasis, pTNM stage, VEGF-A, VEGF-C, LVD, and MVD. SCARA5 overexpression
significantly suppressed cell proliferation, colony formation, invasion, and
migration, and induced G0/G1 arrest and apoptosis of ZR-75-30 cells. SCARA5
decreased the phosphorylation of ERK1/2, AKT, and STAT3, and downregulated
downstream signaling effectors, including MMP-2, 3, and 9, VEGF-A, VEGF-C, Bax,
Cyclin B1, Cyclin D1, and Cyclin E1, and upregulated E-cadherin, Bcl-2, and
caspase 3. SCARA5 is associated with multiple signaling pathways and plays a
critical role in the progression and metastasis of breast cancer. The present
results provide the first evidence that SCARA5 inhibits lymphangiogenesis by
downregulating VEGF-C, thereby inhibiting breast cancer lymphatic metastasis.
PMID- 28497373
TI - Morphological, Histobiochemical and Molecular Characterisation of Low Lignin
Phloem Fibre (llpf) Mutant of Dark Jute (Corchorus olitorius L.).
AB - Lignin is a versatile plant metabolite challenging high-end industrial
applications of several plant products including jute. Application of
developmental mutant in regulation of lignification in jute may open up door for
much awaited jute based diversified products. In the present study, a novel dark
jute (Corchorus olitorius L.) mutant with low lignin (7.23%) in phloem fibre
being compared to wild-type JRO 204 (13.7%) was identified and characterised.
Unique morphological features including undulated stem, petiole and leaf vein
distinguished the mutant in gamma ray irradiated mutant population. Histological
and biochemical analysis revealed reduced lignification of phloem fibre cells of
the plant. RT-PCR analysis demonstrated temporal transcriptional regulation of
CCoAMT1 gene in the mutant. The mutant was found an extremely useful model to
study phloem fibre developmental biology in the crop besides acting as a donor
genetic stock for low lignin containing jute fibre in dark jute improvement
programme.
PMID- 28497374
TI - The effect of insulin administration on c-peptide in critically ill patients with
type 2 diabetes.
AB - BACKGROUND: In critically ill patients with permissive hyperglycemia, it is
uncertain whether exogenous insulin administration suppresses or enhances c
peptide secretion (a marker of pancreatic beta-cell response). We aimed to
explore this effect in patients with type 2 diabetes. METHODS: We prospectively
enrolled a cohort of 45 critically ill patients with type 2 diabetes managed
according to a liberal glucose protocol (target blood glucose 10-14 mmol/l). We
recorded the administration of insulin and oral hypoglycemic agents and measured
plasma c-peptide as surrogate marker of endogenous insulin secretion on the first
two consecutive days in ICU. RESULTS: Overall, 20 (44.4%) patients required
insulin to achieve target blood glucose. Insulin-treated patients had higher
glycated hemoglobin A1c, more premorbid insulin-requiring type 2 diabetes, and
greater blood glucose levels but lower c-peptide levels on admission. Premorbid
insulin-requiring diabetes was independently associated with lower admission c
peptide, whereas greater plasma creatinine was independently associated with
higher levels. Increases in c-peptide were positively correlated with an increase
in blood glucose both in patients who did (r = 0.54, P = 0.01) and did not (r =
0.56, P = 0.004) receive insulin. However, insulin administration was
independently associated with a greater increase in c-peptide (P = 0.04). This
association was not modified by the use of oral insulin secretagogues.
CONCLUSIONS: C-peptide, a marker of beta-cell response, responds to and is
influenced by glycemia and renal function in critically ill patients with type 2
diabetes. In addition, in our cohort, exogenous insulin administration was
associated with a greater increase in c-peptide in response to hyperglycemia.
Trial Registration Australian New Zealand Clinical Trials Registry
(ACTRN12615000216516).
PMID- 28497375
TI - Pearls: Clinical Application of Ranawat's Sign.
PMID- 28497376
TI - Application of electrospun fibers for female reproductive health.
AB - Here, we present the current challenges in women's reproductive health and the
current state-of-the-art treatment and prevention options for STI prevention,
contraception, and treatment of infections. We discuss how the versatile platform
of electrospun fibers can be applied to each challenge, and postulate at how
these technologies could be improved. The void of approved electrospun fiber
based products yields the potential to apply this useful technology to a number
of medical applications, many of which are relevant to women's reproductive
health. Given the ability to tune drug delivery characteristics and three
dimensional geometry, there are many opportunities to pursue new product designs
and routes of administration for electrospun fibers. For each application, we
provide an overview of the versatility of electrospun fibers as a novel dosage
form and summarize their advantages in clinical applications. We also provide a
perspective on why electrospun fibers are well-suited for a variety of
applications within women's reproductive health and identify areas that could
greatly benefit from innovations with electrospun fiber-based approaches.
PMID- 28497377
TI - [Choosing wisely recommendations in hematology and oncology].
AB - Many new diagnostic and therapeutic options have been introduced in the field of
hematology and medical oncology during recent years. Rational treatment
recommendations are thus of even greater importance. Five presumably underused
measures are recommended (positive recommendations), primarily pertaining to
supportive therapy, but also concerning the selective use of molecular
diagnostics. Recommendations to avoid unnecessary procedures (negative
recommendations) involve a possible excessive use of anticancer therapy and
imaging, and insufficiently selective use of growth factors, antiemetics, and
targeted therapies.
PMID- 28497378
TI - [How does physical activity influence mortality?]
PMID- 28497379
TI - [Choosing wisely recommendations in cardiology].
AB - This article describes controversially discussed Choosing wisely recommendations
presented by the German Cardiac Society: anticoagulation therapy in patients with
atrial fibrillation and "only" moderate stroke risk, on the one hand, and goal
directed low-density lipoprotein (LDL) cholesterol-lowering, on the other.
Presuming an adequate regime, patients with atrial fibrillation and only moderate
risk of stroke (CHA2DS2-VASc Score of 1 in men and of 2 in women) also benefit
from anticoagulation therapy, even in elderly patients. In patients with coronary
heart disease, the German Cardiac Society recommends reducing LDL-cholesterol
serum levels with a statin to values lower than 70 mg/dl (1.8 mmol/l) or at least
reducing the basal level by 50%. With this recommendation, the German Cardiac
Society unequivocally prioritizes the "goal-oriented statin therapy" above the
"statin strategy of fixed dose". The reasons for this preference are discussed.
PMID- 28497381
TI - Deep Benign Fibrous Histiocytoma of the Anterior Mediastinum Mimicking
Malignancy.
AB - The following report describes the case of a 43-year-old male smoker that was
referred to the rapid access lung clinic with haemoptysis, chest pain, and
axillary lymphadenopathy-a clinical picture that raised concern for a possible
underlying malignancy. Preliminary investigations revealed elevated D-dimers, low
volume haemoptysis, and a normal chest X-ray, which lowered the index of
suspicion. However, computed tomography (CT) pulmonary angiogram identified a
right hilar mass, several parenchymal cysts, and a large mediastinal mass. In
addition, a left-sided adrenal lesion was also discovered following CT abdomen
pelvis, potentially indicating metastatic disease. Fortunately, a positron
emission tomography scan failed to detect any metabolic activity in either the
right hilar mass, left adrenal lesion or the anterior mediastinal mass. CT-guided
biopsy identified the mediastinal mass as a low-grade spindle cell tumour. Due to
its large size, the mass was surgically resected and confirmed to be a deep
benign fibrous histiocytoma. The significance of this report is to highlight a
clinical presentation suggestive of malignancy but actually resulting from a rare
variant of a benign tumour. The constellation of regional lymphadenopathy,
respiratory and gastrointestinal symptoms, lung cysts, an adrenal tumour, and a
mediastinal mass appeared to suggest a progressive disease pattern more commonly
associated with malignancy.
PMID- 28497382
TI - Attenuation of Sulfur Dioxide Damage to Wheat Seedlings by Co-exposure to Nitric
Oxide.
AB - The protective function of nitric oxide (NO) has been extensively clarified in
plant responses to abiotic stresses. However, little is known about the
regulation of NO in plants exposed to sulfur dioxide (SO2). In the present study,
we found that co-exposure to NO significantly attenuated SO2-induced wheat
seedling growth inhibition. Data showed that NO efficiently prevented SO2
triggered oxidative stress, as indicated by decreasing reactive oxygen species
production, lipid peroxidation, and electrolyte leakage. This might be attributed
to the regulatory role of NO in antioxidative defense, such as increasing the
activities of antioxidative enzymes and the contents of non-enzymatic
antioxidants. The SO2-caused declines in soluble protein and chlorophyll content
were efficiently recovered by NO application. Photosynthetic parameters, such as
net photosynthetic rate, maximum photochemical efficiency, and actual
photochemical efficiency, were protected by NO. In conclusion, this study
demonstrated that during SO2 exposure, co-application of NO can efficiently
alleviate plant damage probably by regulating the antioxidative defense, and
protecting plant photosynthesis-related process.
PMID- 28497383
TI - Form of Dietary Methylmercury does not Affect Total Mercury Accumulation in the
Tissues of Zebra Finch.
AB - Exposure to mercury in humans, other mammals, and birds is primarily dietary,
with mercury in the methylated form and bound to cysteine in the tissues of prey
items. Yet dosing studies are generally carried out using methylmercury chloride.
Here we tested whether the accumulation of total mercury in zebra finch blood,
egg, muscle, liver, kidney or brain differed depending on whether dietary mercury
was complexed with chloride or cysteine. We found no effect of form of mercury on
tissue accumulation. Some previous studies have found lower accumulation of
mercury in tissues of animals fed complexed mercury. Much remains to be
understood about what happens to ingested mercury once it enters the intestines,
but our results suggest that dietary studies using methylmercury chloride in
birds will produce similar tissue accumulation levels to those using
methylmercury cysteine.
PMID- 28497384
TI - Physiological responses to incremental, interval, and continuous counterweighted
single-leg and double-leg cycling at the same relative intensities.
AB - PURPOSE: We compared physiological responses to incremental, interval, and
continuous counterweighted single-leg and double-leg cycling at the same relative
intensities. The primary hypothesis was that the counterweight method would
elicit greater normalized power (i.e., power/active leg), greater
electromyography (EMG) responses, and lower cardiorespiratory demand. METHODS:
Graded-exercise tests performed by 12 men (age: 21 +/- 2 years; BMI: 24 +/- 3
kg/m2) initially established that peak oxygen uptake ([Formula: see text]; 76 +/-
8.4%), expired ventilation ([Formula: see text]; 71 +/- 6.8%), carbon dioxide
production ([Formula: see text]; 71 +/- 6.8%), heart rate (HRpeak; 91 +/- 5.3%),
and power output (PPO; 56 +/- 3.6%) were lower during single-leg compared to
double-leg cycling (main effect of mode; p < 0.05). On separate days,
participants performed four experimental trials, which involved 30-min bouts of
either continuous (50% PPO) or interval exercise [4 * (5-min 65% PPO + 2.5 min
20% PPO)] in a single- or double-leg manner. RESULTS: Double-leg interval and
continuous cycling were performed at greater absolute power outputs but lower
normalized power outputs compared to single-leg cycling (p < 0.001). The average
EMG responses from the vastus lateralis and vastus medialis were similar across
modes (p > 0.05), but semitendinosus was activated to a greater extent for single
leg cycling (p = 0.005). Single-leg interval and continuous cycling elicited
lower mean [Formula: see text], [Formula: see text], [Formula: see text], HR and
ratings of perceived exertion compared to double-leg cycling (p < 0.05).
CONCLUSIONS: Counterweighted single-leg cycling elicits lower cardiorespiratory
and perceptual responses than double-leg cycling at greater normalized power
outputs.
PMID- 28497385
TI - Associations of human skeletal muscle fiber type and insulin sensitivity, blood
lipids, and vascular hemodynamics in a cohort of premenopausal women.
AB - PURPOSE: Cardiometabolic disease remains a leading cause of morbidity and
mortality in developed nations. Consequently, identifying and understanding
factors associated with underlying pathophysiological processes leading to
chronic cardio metabolic conditions is critical. Metabolic health, arterial
elasticity, and insulin sensitivity (SI) may impact disease risk, and may be
determined in part by myofiber type. Therefore, the purpose of this study was to
test the hypothesis that type I myofiber composition would be associated with
high SI, greater arterial elasticity, lower blood pressure, and blood lipids;
whereas, type IIx myofibers would be associated with lower SI, lower arterial
elasticity, higher blood pressure, blood lipids. METHODS: Muscle biopsies were
performed on the vastus lateralis in 16 subjects (BMI = 27.62 +/- 4.71 kg/m2, age
= 32.24 +/- 6.37 years, 43% African American). The distribution of type I, IIa,
and IIx myofibers was determined via immunohistochemistry performed on frozen
cross-sections. Pearson correlation analyses were performed to assess
associations between myofiber composition, SI, arterial elasticity, blood
pressure, and blood lipid concentrations. RESULTS: The percentage of type I
myofibers positively correlated with SI and negatively correlated with systolic
blood pressure SBP, diastolic blood pressure, and mean arterial pressure (MAP);
whereas, the percentage of type IIx myofibers were negatively correlated with SI
and large artery elasticity, and positively correlated with LDL cholesterol, SBP,
and MAP. CONCLUSIONS: These data demonstrate a potential link between myofiber
composition and cardiometabolic health outcomes in a cohort of premenopausal
women. Future research is needed to determine the precise mechanisms in which
myofiber composition impacts the pathophysiology of impaired glucose and lipid
metabolism, as well as vascular dysfunction.
PMID- 28497386
TI - Oral contraceptive pill use and the susceptibility to markers of exercise-induced
muscle damage.
AB - PURPOSE: Firstly, to establish whether oral contraceptive pill (OCP) users are
more susceptible to muscle damage compared to non-users, and secondly, to
establish whether differences can be attributed to differences in patella tendon
properties. METHODS: Nine female OCP users and 9 female non-users participated in
the investigation. Combining dynamometry, electromyography and ultrasonography,
patella tendon properties and vastus lateralis architectural properties were
measured pre and during the first of 6 sets of 12 maximal voluntary eccentric
knee extensions. Serum oestrogen levels were measured on the 7th day of the pill
cycle and the 14th day of menstrual cycle in OCP users and non-users,
respectively. Maximal voluntary isometric knee extension torque loss, creatine
kinase and muscle soreness were measured 48 h pre-damage, post-damage, and 48, 96
and 168 h post-damage. RESULTS: Oestrogen levels were significantly lower in OCP
users compared to non-users (209 +/- 115 and 433 +/- 147 pg/ml, respectively, p =
0.004). Proposed determinants of muscle damage, patella tendon stiffness and
maximal eccentric torque did not differ between OCP users and non-users. The
change in creatine kinase from pre to peak was significantly higher in OCP users
compared to non-users (962 +/- 968 and 386 +/- 474 Ul, respectively, p = 0.016).
There were no other differences in markers of muscle damage. CONCLUSION: Although
our findings suggest that, when compared to non-users, the OCP may augment the
creatine kinase response following eccentric exercise, it does not increase the
susceptibility to any other markers of muscle damage.
PMID- 28497380
TI - From Gene to Behavior: L-Type Calcium Channel Mechanisms Underlying
Neuropsychiatric Symptoms.
AB - The L-type calcium channels (LTCCs) Cav1.2 and Cav1.3, encoded by the CACNA1C and
CACNA1D genes, respectively, are important regulators of calcium influx into
cells and are critical for normal brain development and plasticity. In humans,
CACNA1C has emerged as one of the most widely reproduced and prominent candidate
risk genes for a range of neuropsychiatric disorders, including bipolar disorder
(BD), schizophrenia (SCZ), major depressive disorder, autism spectrum disorder,
and attention deficit hyperactivity disorder. Separately, CACNA1D has been found
to be associated with BD and autism spectrum disorder, as well as cocaine
dependence, a comorbid feature associated with psychiatric disorders. Despite
growing evidence of a significant link between CACNA1C and CACNA1D and
psychiatric disorders, our understanding of the biological mechanisms by which
these LTCCs mediate neuropsychiatric-associated endophenotypes, many of which are
shared across the different disorders, remains rudimentary. Clinical studies with
LTCC blockers testing their efficacy to alleviate symptoms associated with BD,
SCZ, and drug dependence have provided mixed results, underscoring the importance
of further exploring the neurobiological consequences of dysregulated Cav1.2 and
Cav1.3. Here, we provide a review of clinical studies that have evaluated LTCC
blockers for BD, SCZ, and drug dependence-associated symptoms, as well as rodent
studies that have identified Cav1.2- and Cav1.3-specific molecular and cellular
cascades that underlie mood (anxiety, depression), social behavior, cognition,
and addiction.
PMID- 28497387
TI - Changes in light-, moderate-, and vigorous-intensity physical activity and
changes in depressive symptoms in breast cancer survivors: a prospective
observational study.
AB - PURPOSE: Despite the recommendations for cancer survivors to engage in either
moderate or vigorous physical activity, light-intensity physical activity may
also have beneficial effects on mental health. The purpose of this study was to
examine the associations between light, moderate, and vigorous physical activity
and depressive symptoms in breast cancer survivors over 1 year post-treatment.
METHODS: Participants (N = 201) were a sample of breast cancer survivors who self
reported depressive symptoms and wore an accelerometer for seven consecutive days
to measure physical activity, on five occasions every 3 months post-treatment for
cancer. RESULTS: Based on the results of hierarchical linear modeling, relative
to others (i.e., between-person effects) and to oneself (i.e., within-person
effects), higher levels of light- and moderate-intensity physical activity, but
not vigorous-intensity physical activity, were associated with lower scores of
depressive symptoms. CONCLUSIONS: In the first year post-treatment, increases in
light- and moderate-intensity physical activity, but not vigorous-intensity
physical activity, were associated with lower scores of depressive symptoms in
relation to other study participants (i.e., between-person effects) and when
participants were compared to their own typical levels of physical activity
(i.e., within-person effects). The findings may have implications for physical
activity recommendations following treatment for breast cancer as light-intensity
physical activity may play a role in mitigating depressive symptoms over the
first year.
PMID- 28497388
TI - First experience with electronic feedback of the Psychosocial Assessment Tool in
pediatric cancer care.
AB - PURPOSE: The Psychosocial Assessment Tool (PAT) is a brief family screener,
identifying families at universal or elevated risk for psychosocial problems.
This study aimed to determine the feasibility and usability of the electronic PAT
(ePAT) in pediatric cancer care. METHODS: Eighty-six parents of newly diagnosed
children with cancer (0-18 years) agreed to participate and registered at the
website www.hetklikt.nu (58%). Seventy-five families completed the ePAT at
approximately 1 month post-diagnosis. Answers were transformed into an electronic
PROfile (PAT ePROfile) and fed back to the psychosocial team. Team members
completed a semi-structured evaluation questionnaire. Feasibility was measured as
the percentage of website registrations, completed ePATs, and PAT ePROfiles
reviewed or discussed by the team. Usability included perceived match of the PAT
ePROfile with the team's own risk estimation, perceived added value, and
perceived actions undertaken as a result of the PAT ePROfile. RESULTS:
Feasibility was 70% for website registration, 87% for completed ePATs, 85% for
PAT ePROfile reviewing, and 67% for ePROfile discussion. Team members reported
that the PAT ePROfile matched with their own risk estimation (M = 7.92, SD =
1.88) and did not provide additional information (M = 2.18, SD = 2.30). According
to the team, actions were undertaken for 25% of the families as a result of the
PAT ePROfile. More actions were undertaken for families with elevated risk scores
compared to universal risk scores (p = .007). CONCLUSIONS: Implementation of the
ePAT seems generally feasible, but it is not always clear how this screener adds
to current clinical practice. Strategies should be developed together with team
members to improve quick exchange of ePAT results and allocate care according to
the needs of the families.
PMID- 28497390
TI - Garlicin post-conditioning suppresses adhesion molecules in a porcine model of
myocardial ischemia-reperfusion injury.
AB - OBJECTIVES: To evaluate whether garlicin post-conditioning can attenuate
myocardial ischemiareperfusion injury in a catheter-based porcine model of acute
myocardial infarction (AMI) by affecting adhesion molecules integrin beta1/CD29
and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31). METHODS: Twenty
two swine were devided into 3 groups: 6 in a sham-operation group, and 8 each in
the model and garlicin groups. AMI porcine model was established in the model and
garlicin groups. The distal parts of the left anterior descending coronary artery
in the animals of the model and garlicin groups were occluded by dilated balloon
for 2 h, followed by reperfusion for 3 h. Garlicin (1.88 mg/kg) was injected over
a period of 1 h, beginning just before reperfusion, in the garlicin group. Real
time polymerase chain reaction, immunohistochemistry and Western blot were
carried out to detect mRNA and protein expressions of CD29 and CD31 3 h after
reperfusion. RESULTS: Hematoxylin-eosin staining showed a better myocardial
structure in the garlicin group after reperfusion. Compared to the model group,
garlicin inhibited both the mRNA and protein expression of CD29 and CD31 in
reperfusion area and no-reflflow area (P<0.05 respectively). CONCLUSIONS:
Garlicin post-conditioning induced cardio-protection against myocardial ischemia
reperfusion injury in this catheter-based porcine model of AMI. The cardio
protective effect of garlicin is possibly owing to suppression of production of
CD29 and CD31, by inhibition of the mRNA expression of CD29 and CD31.
PMID- 28497389
TI - Elucidating and engineering thiopeptide biosynthesis.
AB - Initially discovered in the mid-twentieth century, thiopeptides constitute a
diverse family of bacterially produced natural products exhibiting a remarkable
array of biological properties. Only in the last several years have the details
of thiopeptide biosynthesis been uncovered by a combination of genomic, genetic,
and biochemical approaches. Thiopeptides are now known to be ribosomally
synthesized and subsequently densely modified to carry azol(in)es, dehydro amino
acids, and various other pathway-specific decorations. The defining feature of
thiopeptides is a central six-membered nitrogenous ring that constrains peptide
macrocycles of varying sequences and sizes. Recent landmark studies have defined
the precisely orchestrated posttranslational modification cascade culminating in
thiopeptide product formation. Because diverse thiopeptides are processed by a
relatively small number of well-conserved enzymes, it has been suggested that
artificial diversification of the precursor peptide could allow a vast new
chemical space to be explored for clinically important activities. The success of
this strategy depends on the plasticity of thiopeptide processing machinery, an
open question that warrants further investigation. There is an urgent need
therefore to leverage established thiopeptide research platforms to investigate
substrate-enzyme specificity and devise intelligent diversification strategies
for library generation. Meanwhile, the distinct genomic signatures of conserved
thiopeptide-associated genes will enable the continued mining of nature for novel
compounds and processing enzymes.
PMID- 28497391
TI - Effect of Lang-Chuang-Ding Decoction () on DNA Methylation of CD70 Gene Promoter
in Peripheral Blood Mononuclear Cells of Female Patients with Systemic Lupus
Erythematosus.
AB - OBJECTIVE: To investigate the effect of Lang-chuang-ding Decoction (, LCD) on the
expression of DNA methylation of CD70 gene promoter in peripheral blood
mononuclear cells (PBMCs) of females with systemic lupus erythematosus (SLE).
METHODS: PBMCs isolated from female patients with SLE or healthy donors were
cultured and treated with LCD medicated serum or normal serum for 24 or 48 h. The
mRNA expressions of CD70 gene in PBMCs were detected by reverse transcription
polymerase chain reaction (PCR); the DNA methylation of the CD70 gene promoter
region was detected by methylation-specific PCR. RESULTS: After treated with
medicated serum for 48 h, the mRNA expression levels of CD70 in PBMCs of SLE
patients were signifificantly higher than those of healthy donors (P<0.05); the
DNA methylation levels of CD70 promoter region in PBMCs of SLE patients treated
with medicated serum for 48 h were signifificantly higher than those treated with
fetal bovine serum (P<0.01). CONCLUSION: LCD could inhibit CD70 gene expression
in PBMCs of SLE patients by promoting the DNA methylation of CD70 gene promoter.
PMID- 28497392
TI - Xuebijing Injection () increases early survival rate by alleviating pulmonary
vasopermeability in rats subjected to severe burns.
AB - OBJECTIVE: To investigate the effects of Xuebijing Injection (, XBJ) on survival
rate and pulmonary vasopermeability in a rat model of severe scald injury.
METHODS: Rats were divided into two experiments: experiment 1 was monitored for
12 h post-injury for survival analysis after severe burns; in experiment 2, rats
were killed for determination of pulmonary vascular permeability and pro
inflflammatory mediators. In both experiments, rats were subject to third-degree
50% total body surface area (TBSA) burns or sham injury followed by XBJ or normal
saline (NS) treatment. In addition, rat pulmonary microvascular endothelium cells
(PMECs) were pretreated with either XBJ or phosphate buffer saline (PBS), and
then subjected to sham serum or scald serum stimulation for 2 or 6 h, followed by
transwell examination for the permeability of PMECs. Meanwhile, pro
inflflammatory mediators in PMECs culture supernatant were also investigated.
RESULTS: The average survival time in the scald+XBJ group was 582.1+/-21.2 min,
which was signifificantly longer than that in the scald + NS group (345.8+/-25.4
min, P<0.01). Plasma levels of tumor necrosis factor-alpha (TNF-alpha), E
selectin, interleukin-6 (IL-6), vascular permeability and water content of lung
tissues were signifificantly increased in animals after severe burns (P<0.01).
However, administration of XBJ signifificantly decreased these levels in plasma
and lung tissue. In in vitro cell experiments, XBJ markedly attenuated
permeability in PMECs monolayer and reduced the levels of TNF-alpha, IL-6 and
soluble E-selectin after stimulation with scald serum (P<0.01). CONCLUSIONS: XBJ
increases early survival rate by alleviating pulmonary vasopermeability and
inhibiting pro-inflflammatory mediators in rats subjected to lethal scald injury.
XBJ may be a potent drug in treatment of severe burns.
PMID- 28497394
TI - Embolic effects of Bletilla striata microspheres in renal artery and transplanted
VX2 liver tumor model in rabbits.
AB - OBJECTIVES: To evaluate the characteristics of Bletilla striata microspheres
(BSMs) and its effects as an embolic agent in a rabbit model. METHODS: BSMs were
prepared with an emulsifification-cool condensation-chemical cross-linking
method. The characteristics of BSMs in vitro were observed. Embolization
experiments were performed in renal artery of rabbit and in a rabbit liver VX2
carcinoma model. Seventy-two New Zealand rabbits were divided into 2 groups, and
the right renal artery was embolized with BSMs (200 MUm in diameter) in the
experimental group and with polyvinyl alcohol (PVA) of the same size in the
control group. The pathological findings were examined with hematoxylin-eosin and
Masson stainings. Liver and renal functions were tested before and after
embolization. VX2 tumor was transplanted in 15 New Zealand rabbits, which were
randomly divided into 3 groups (n=5). Group A were treated with saline, group B
with a mixture of doxorubicin and lipiodol, and group C with hepatic arterial
infusion of BSMs (200 MUm in diameter). Tumor growth rate was evaluated by
magnetic resonance imaging scan. Apoptosis-related factors (bax, bcl-2) and tumor
vascular endothelial cell growth factor (VEGF) were evaluated through
immunohistochemical staining. RESULTS: The characteristics of BSMs in vitro were
in full compliance with the requirements for use in interventional procedures. In
the renal artery embolization experiment, after BSMs intervention, it was more
diffificult to form collateral circulation than that with PVAs, and the kidney
manifested atrophy and calcifification. There were no signifificant difference of
liver and renal functions in rabbits between groups. In the liver VX2 carcinoma
embolization experiment, compared with group A, the growth rate of VX2 liver
tumor and Bcl-2 levels was reduced, while apoptosis index, Bax, and VEGF were
increased in group B (P<0.05). There were no signifificant difference between
groups B and C (P>0.05). CONCLUSIONS: The characteristics of BSMs in vitro and in
vivo meet the requirements for its use as an embolic agent in interventional
approaches.
PMID- 28497393
TI - Effect of Miscanthus sinensis var. purpurascens Flower Extract on Proliferation
and Molecular Regulation in Human Dermal Papilla Cells and Stressed C57BL/6 Mice.
AB - OBJECTIVES: To investigate the hair growth-promoting effect of Miscanthus
sinensis var. purpurascens (MSP) flower extracton on in vitro and in vivo models.
METHODS: MSP flower extract was extracted in 99.9% methanol and applied to
examine the proliferation of human dermal papilla cells (hDPCs) in vitro at the
dose of 3.92-62.50 MUg/mL and hair growth of C57BL/6 mice in vivo at the dose of
1000 MUg/mL. The expression of transforming growth factor beta1 (TGF-beta1),
hepatocyte growth factor (HGF), beta-catenin, substance P was measured by
relative quantitative realtime polymerase chain reaction. Histopathological and
immunohistochemical analysis were performed. RESULTS: MSP (7.81 MUg/mL) down
regulated TGF-beta1 and up-regulated HGF and beta-catenin in hDPCs (P<0.01). MSP
(1000 MUg/mL)-treated mice showed the earlier transition of hair follicles from
the telogen to the anagen phase. The number of mast cells was lower in the MSP
treated mice than in other groups (P<0.05 vs. NCS group). Substance P and TGF
beta1 were expressed in hair follicles and skin of the MSP group lower than that
in negative control. Stem cell factor in hair follicles was up-regulated in the
MSP-treated mice (P<0.01). CONCLUSIONS: The MSP flower extract may have hair
growth-promotion activities.
PMID- 28497395
TI - Cardioprotective effects of Qishen Granule () on sarcoplasmic reticulum Ca2+
handling in heart failure rats.
AB - OBJECTIVE: To assess the effects of Qishen Granule (, QSG) on sarcoplasmic
reticulum (SR) Ca2+ handling in heart failure (HF) model of rats and to explore
the underlying molecular mechanisms. METHODS: HF rat models were induced by left
anterior descending coronary artery ligation surgery and high-fat diet feeding.
Rats were randomly divided into sham (n=10), model (n=10), QSG (n=12, 2.2 g/kg
daily) and metoprolol groups (n=12, 10.5 mg/kg daily). The therapeutic effects of
QSG were evaluated by echocardiography and blood lipid testing. Intracellular
Ca2+ concentration and sarco-endoplasmic reticulum ATPase 2a (SERCA2a) activity
were detected by specifific assay kits. Expressions of the critical regulators in
SR Ca2+ handling were evaluated by Western blot and real-time quantitative
polymerase chain reaction. RESULTS: HF model of rats developed ventricular
remodeling accompanied with calcium overload and defective Ca2+ release-uptake
cycling in cardiomyocytes. Treatment with QSG improved contractive function,
attenuated ventricular remodeling and reduced the basal intracellular Ca2+ level.
QSG prevented defective Ca2+ leak by attenuating hyperphosphorylation of
ryanodine receptor 2, inhibiting expression of protein kinase A and up-regulating
transcriptional expression of protein phosphatase 1. QSG also restored Ca2+
uptake by up-regulating expression and activity of SERCA2a and promoting
phosphorylation of phospholamban. CONCLUSION: QSG restored SR Ca2+ cycling in HF
rats and served as an ideal alternative drug for treating HF.
PMID- 28497396
TI - Progressive Muscle Relaxation Combined with Chinese Medicine Five-Element Music
on Depression for Cancer Patients: A Randomized Controlled Trial.
AB - OBJECTIVES: To evaluate the effects of progressive muscle relaxation training
(PMRT) combined with fifive elements music therapy of Chinese medicine (CM) for
improving anxiety and depression of cancer patients. METHODS: From June 2015 to
March 2016, 60 cancer patients were included into the study. The patients were
randomly assigned to a control group and a treatment group by envelope
randomization, receiving PMRT and PMRT plus CM five elements music therapy,
respectively, for 8 weeks. Hospital Anxiety and Depression Scale (HADS), Benefit
Finding Scales (BFS), Functional Assessment of Chronic Illness Therapy-Spiritual
(FACIT-Sp), and Intervention Expectations Questionnaire (IEQU) were adopted to
assess the depression of the two groups before and after the treatment. RESULTS:
Four cases dropped out during the study, and 29 cases in the treatment group and
27 in the control group were included in the fifinal analysis. Prior to the
treatments, the baselines of the 4 questionnaires in the two groups showed no
difference. After the 8-week treatment, the treatment group presented better
levels of HADS, BFS and FACIT-Sp scores compared with the control group (P<0.05).
Among the single items of HADS, 4 items involving vexation, feeling fifidgeted,
pleasure and prospecting the future in the treatment group were improved compared
with the control group (P<0.05). CONCLUSIONS: As a simple and reliable and
effective intervention, PMRT combined with fifive elements music therapy
mitigated anxiety and depression of cancer patients. Cancer patients have been
found to respond well to psychological intervention in areas regarding
stabilisation of emotions, disease awareness, and therapeutic compliance. This
brings about a great difference in improving their quality of life and
psychological state, offers an effective approach to better self-management in
cancer treatment.
PMID- 28497397
TI - Xuebijing Injection () and Resolvin D1 Synergize Regulate Leukocyte Adhesion and
Improve Survival Rate in Mice with Sepsis-Induced Lung Injury.
AB - OBJECTIVE: To investigate the effect of combined application of Xuebijing
Injection ( , XBJ) and resolvin D1 (RvD1) on survival rate and the underlying
mechanisms in mice with sepsisinduced lung injury. METHODS: The cecal ligation
and puncture (CLP) method was used to develop a mouse sepsis model. Specific
pathogen free male C57BL/6 mice were randomly divided into 5 groups (n=20 each):
sham, CLP, CLP+XBJ, CLP+RvD1 and CLP+XBJ+RvD1. After surgery, mice in the
CLP+XBJ, CLP+RvD1 and CLP+XBJ+RvD1 groups were given XBJ (25 MUL/g body weight),
RvD1 (10 ng/g body weight), and their combination (the same dose of XBJ and
RvD1), respectively. In each group, 12 mice were used to observe 1-week survival
rate, while the rest were executed at 12 h. Whole blood was collected for flow
cytometric analysis of leukocyte adhesion molecules CD18, lung tissues were
harvested for observing pathological changes, and testing the activity of
myeloperoxidase (MPO) and the expression of intercellular cell adhesion molecule
1 (ICAM-1). RESULTS: Compared with the CLP group, the histopathological damage of
the lung tissues was mitigated, MPO activity was decreased in the CLP+XBJ and
CLP+RvD1 groups (P<0.05). In addition, the 1-week survival rate was improved,
proportion of CD18-expressing cells in whole blood and ICAM-1 protein expression
in lung tissue were decreased in the CLP+XBJ+RvD1 group (P<0.05 or P<0.01).
CONCLUSIONS: XBJ together with RvD1 could effectively inhibit leukocyte adhesion,
reduce lung injury, and improve the survival rate of mice with sepsis.
PMID- 28497399
TI - Money, Social Relationships and the Sense of Self: The Consequences of an
Improved Financial Situation for Persons Suffering from Serious Mental Illness.
AB - During a 9-month period, 100 persons with SMI were given approx. 73 USD per month
above their normal income. Sixteen of the subjects were interviewed. The
interviews were analysed according to the methods of thematic analysis. The money
was used for personal pleasure and to re-establish reciprocal relations to
others. The ways in which different individuals used the money at their disposal
impacted their sense of self through experiences of mastery, agency, reciprocity,
recognition and security. The findings underline the importance of including
social circumstances in our understanding of mental health problems, their
trajectories and the recovery process.
PMID- 28497400
TI - Nothing but Mammals? Review of Tim Clutton-Brock's Mammal Societies : (Wiley,
2016).
PMID- 28497398
TI - Early markers of myocardial ischemia: from the experimental model to forensic
pathology cases of sudden cardiac death.
AB - The goal of this study was to assess whether early markers of myocardial
ischemia, identified in a previous experimental work, can be applied in forensic
pathology cases of sudden, ischemic cardiac death. These markers include
desphosphorylated connexin 43 (Cx43), JunB, TUNEL assay, myoglobin, and troponin
T. Fourteen cases of sudden cardiac death with gross and/or histological signs of
myocardial infarction and 14 cases of sudden cardiac death with signs of early
ischemia at histology and positive immunoreactions for fibronectin and C5b-9 were
investigated. The control group was represented by 15 hanging (global hypoxia)
cases. Immunohistochemical reactions were classified into four degrees and
compared among groups. Cx43 and JunB were significantly more expressed in hanging
than in ischemia/infarction, but they showed a different distribution in the
tissue (sub-endocardial in ischemia/infarction, diffuse in hanging) and a
different intensity of the signal. TUNEL assay was significantly more expressed
in the group of early ischemia than in myocardial infarction. Myoglobin and
troponin T did not show any significantly different expression among the three
groups. Depletion markers have a limited application in forensic cases, and this
is mostly because positive (depleted) areas are difficult to distinguish from
artifactually paler areas. Nuclear markers (JunB and TUNEL), on the other hand,
require a well-trained eye and a high magnification in order to be distinguished.
Cx43, JunB, and TUNEL assays were confirmed to be early, sensitive markers for
myocardial ischemia. Nonetheless, they are not specific, as they are expressed in
global hypoxia as well, but with a different tissular distribution.
PMID- 28497401
TI - Using a Film Intervention in Early Addiction Treatment: a Qualitative Analysis of
Process.
AB - PURPOSE: There is a need for knowledge about how self-help materials can be made
useful in treatment for Substance Abuse Disorders (SUD), as a supplement to
ongoing treatment, or as independent tools for change. OBJECTIVE: In this study,
we explored the use of self-help films in early addiction treatment, taking into
account both patient and therapist perspectives, as well as dyadic functions. We
explored how active mechanisms might be related to intervention format and
implementation context. A secondary aim was to examine the potential mechanisms
related to the specific content of the intervention: mindfulness and acceptance
psychoeducation. METHODS: A qualitative exploratory research design, including a
general inductive analytic approach, constructivist grounded theory, and source
triangulation features, was used to code and analyze interview material. Emerging
themes were developed into concepts, and finally an operational model.
Participants included 12 patients and 22 therapists, in in-/outpatient addiction
clinics, all in urban areas of Norway. The purpose of the design was empirical
grounding of developed concepts, to promote different potential user perspectives
(patients' and therapists') and obtain process data. RESULTS: The core concept
constructed, "Alliance as experiential process," gives a description of the data
where patients and therapists accept or reject the film as a result of an
experience process conceptualized as alliance formation. The alliance process
model reflects the observation that patients constructed alliances autonomously,
while therapists built alliances indirectly through their patients' experiences.
CONCLUSIONS: Use of a self-help film may be a helpful adjunct to face-to-face
therapy for patients who create a personally meaningful attachment to the film.
Mindfulness/acceptance may offer one basic framework for such connection to take
place.
PMID- 28497403
TI - Locally advanced rectal cancer: predicting non-responders to neoadjuvant
chemoradiotherapy using apparent diffusion coefficient textures.
AB - PURPOSE: The purpose of the study is to evaluate whether apparent diffusion
coefficient (ADC) textures could identify patient with locally advanced rectal
cancer (LARC) who would not respond to neoadjuvant chemoradiotherapy (NCRT).
METHOD: Twenty-six patients who underwent MRI including diffusion-weighted
imaging at a 3.0 T system before NCRT were enrolled. Texture analysis of pre
therapy ADC mapping was carried out, and a total of 133 ADC textures as well as
routine mean ADC value of the primary tumor were extracted for each patient.
Texture parameters and mean ADC were compared between responsive group and non
responsive group. Logistic regression was used to determine the independent
predictors for non-responders. Receiver operating characteristic curve (ROC) was
performed to evaluate the predictive performance of the significant parameters.
RESULTS: Eighteen of the 133 texture parameters significantly differed between
responsive and non-responsive groups (p < 0.05). Further, energy variance and
SdGa47 were identified as independent predictors for non-responders to NCRT; this
logistic model achieved an area under the curve (AUC) of 0.908. CONCLUSION:
Texture analysis based on pre-therapy ADC mapping could potentially be helpful to
identify patients with LARC who would not respond to NCRT.
PMID- 28497402
TI - Impact of resection versus no resection of the primary tumor on survival in
patients with colorectal cancer and synchronous unresectable metastases: protocol
for a randomized multicenter study (CR4).
AB - PURPOSE: The purpose of this study was to determine whether patients diagnosed
with colorectal cancer and synchronous unresectable metastases (stage IV) can
benefit from resection of the primary tumor in terms of an improvement in cancer
specific survival. METHODS: Stage IV colorectal cancer patients are eligible for
inclusion in a randomized multicenter study carried out in 22 hospitals
throughout Spain. Exclusion criteria are rectal tumors below 12 cm from the anal
verge or locally advanced tumors, multiple bone or central nervous system
metastases, and history of another primary cancer. The parallel design of the
trial includes an arm of systemic chemotherapy alone versus an arm of resection
of the primary tumor plus systemic chemotherapy after surgery. The primary
endpoint of the study is cancer-specific survival that is assessed with a minimum
follow-up of 24 months. Secondary endpoints are postoperative morbidity and
mortality associated with resection of the primary tumor, complications and need
of surgery in patients treated with systemic chemotherapy only, safety of
systemic chemotherapy in both treatment strategies, and quality of life.
CONCLUSIONS: Confirmation of a survival benefit of surgical resection of the
primary tumor in stage IV colorectal cancer patients not amenable to curative
therapy is very relevant from a clinical and societal perspective, particularly
considering the increase in the incidence and prevalence of colorectal cancer in
developed countries. ClinicalTrials.gov Identifier: NCT02015923.
PMID- 28497405
TI - Multimodality imaging findings in rhabdomyolysis and a brief review of
differential diagnoses.
AB - Rhabdomyolysis has traditionally been a clinical diagnosis with healthcare
providers utilizing historical context, physical exam, and laboratory data to
arrive at a diagnosis. However, there are myriad imaging findings that may be
corroborative and support the presumptive diagnosis. This paper seeks to review
imaging findings associated with rhabdomyolysis using different modalities
including radiography, sonography, computed tomography (CT), magnetic resonance
imaging (MRI), and bone scintigraphy.
PMID- 28497404
TI - Sexual dysfunction following rectal cancer surgery.
AB - INTRODUCTION: Sexual and urological problems after surgery for rectal cancer are
common, multifactorial, inadequately discussed, and untreated. The urogenital
function is dependent on dual autonomic sympathetic and parasympathetic
innervation, and four key danger zones exist that are at risk for nerve damage
during colorectal surgery: one of these sites is in the abdomen and three are in
the pelvis. The aim of this study is to systematically review the epidemiology of
sexual dysfunction following rectal cancer surgery, to describe the anatomical
basis of autonomic nerve-preserving techniques, and to explore the scientific
evidence available to support the laparoscopic or robotic approach over open
surgery. METHODS: According to the PRISMA guidelines, a comprehensive literature
search of studies evaluating sexual function in patients undergoing rectal
surgery for cancer was performed in Medline, Scopus, Web of Science, Embase, and
Cochrane Central Register of controlled trials. RESULTS: An increasing number of
studies assessing the incidence and prevalence of sexual dysfunction following
multimodality treatment for rectal cancer has been published over the last 30
years. Significant heterogeneity in the prevalence of sexual dysfunction is
reported in the literature, with rates between 5 and 90%. CONCLUSIONS: There is
no evidence to date in favor of any surgical approach (open vs laparoscopic vs
robotic). Standardized diagnostic tools should be routinely used to prospectively
assess sexual function in patients undergoing rectal surgery.
PMID- 28497406
TI - Assessing the gap in female authorship in the journal Emergency Radiology: trends
over a 20-year period.
AB - PURPOSE: To examine trends in female authorship in the journal Emergency
Radiology from January 1994 to December 2014. METHODS: We obtained institutional
review board approval for our study. We retrospectively reviewed a total of 1617
articles published in the journal Emergency Radiology over a 20-year period.
Original articles, case reports, review articles, and pictorial essays were
included. The first and last position author's gender was categorized as female
or male. We analyzed trends by comparing the first and last position authors of
original articles from the first and last year reviewed. We utilized Chi-square
test for statistical analysis, with a p value <0.05 noted as significant.
RESULTS: One thousand four hundred twenty articles met our inclusion criteria.
There were 1420 first position authors and 1295 last position authors. There were
125 articles that had a sole author-these authors were considered as first
position authors only. We determined, as best as possible, the gender of 96% of
the authors. Overall, female authors were 21% of first position authors (290 of
1368) and 15% of last position authors (183 of 1246). Thirty-two percent of
articles with female last position authors also had female first position authors
(58 of 183). There was a statistically significant increase in female last
position authors, from 12.9% in 1994 to 21.3% in 2014 (p = 0.026), a non
significant increase in female first position authors, from 17.5% in 1994 to
20.9% in 2014 (p = 0.514), and a non-significant increase in articles with both a
first and last female author, from 25% in 1994 to 35% in 2014 (p = 0.593).
CONCLUSION: Over the last 20 years, there has been a statistically significant
upward trend in female last position authors publishing in the journal Emergency
Radiology.
PMID- 28497407
TI - Tobacco use is not associated with groin hernia repair, a population-based study.
AB - PURPOSE: The pathogenesis of groin hernia is not fully understood and some
suggested risk factors are debatable. This population-based study evaluates the
association between groin hernia repair and tobacco use. METHOD: An observational
study based on register linkage between the Swedish Hernia Register and the
Vasterbotten Intervention Program (VIP). All primary groin hernia repairs
performed from 2001 to 2013 in the county of Vasterbotten, Sweden, were included.
RESULTS: VIP provided data on the use of tobacco in 102,857 individuals. Neither
smoking nor the use of snus, increased the risk for requiring a groin hernia
repair. On the contrary, heavy smoking decreased the risk for men, HR 0.75 (95%
CI 0.58-0.96), as did having a BMI over 30 kg/m2 HR (men) 0.33 (95% CI 0.27
0.40). CONCLUSION: Tobacco use is not a risk factor for requiring a groin hernia
repair, whereas having a low BMI significantly increases the risk.
PMID- 28497408
TI - Novel Turn-on Fluorescence Probes for Al3+ Based on Conjugated Pyrazole Schiff
Base.
AB - One novel turn-on fluorescence probe founded on conjugated pyrazole Schiff base
for detecting Al3+ was invented. The UV-vis and fluorescence spectrometer were
employed to explore optical properties of this probe. The results got from those
experiments indicated that this fluorescence probe manifested excellent
sensitivity and selectivity for Al3+ compared with other cations examined(Ag+,
Co2+, Mg2+, Cu2+, Ni2+, Pb2+,and Zn2+). In addition, this probe displayed a more
rapid response and remained stable between pH 6 and 9 by investigating the
fluorescence intensity under different response time and various pH values.
Remarkably, the detection limit for Al3+ could lower to 1.0*10-9M. Therefore, the
probe could be potentially applied to the environment for the detection of Al3+,
and the availability in biological range of pH that could be further studied to
make this probe apply to biological systems in the future.
PMID- 28497409
TI - A Rapid and Reliable Method for Total Protein Extraction from Succulent Plants
for Proteomic Analysis.
AB - Crassulacean acid metabolism plants have some morphological features, such as
succulent and reduced leaves, thick cuticles, and sunken stomata that help them
prevent excessive water loss and irradiation. As molecular constituents of these
morphological adaptations to xeric environments, succulent plants produce a set
of specific compounds such as complex polysaccharides, pigments, waxes, and
terpenoids, to name a few, in addition to uncharacterized proteases. Since all
these compounds interfere with the analysis of proteins by electrophoretic
techniques, preparation of high quality samples from these sources represents a
real challenge. The absence of adequate protocols for protein extraction has
restrained the study of this class of plants at the molecular level. Here, we
present a rapid and reliable protocol that could be accomplished in 1 h and
applied to a broad range of plants with reproducible results. We were able to
obtain well-resolved SDS/PAGE protein patterns in extracts from different members
of the subfamilies Agavoideae (Agave, Yucca, Manfreda, and Furcraea), Nolinoideae
(Dasylirion and Beucarnea), and the Cactaceae family. This method is based on the
differential solubility of contaminants and proteins in the presence of acetone
and pH-altered solutions. We speculate about the role of saponins and high
molecular weight carbohydrates to produce electrophoretic-compatible samples. A
modification of the basic protocol allowed the analysis of samples by
bidimensional electrophoresis (2DE) for proteomic analysis. Furostanol glycoside
26-O-beta-glucosidase (an enzyme involved in steroid saponin synthesis) was
successfully identified by mass spectrometry analysis and de novo sequencing of a
2DE spot from an Agave attenuata sample.
PMID- 28497410
TI - Could monopronucleated ICSI zygotes be considered for transfer? Analysis through
time-lapse monitoring and PGS.
AB - PURPOSE: The purpose of this study was to investigate the chromosomal
constitution and the developmental potential of intracytoplasmic sperm injection
(ICSI) deriving embryos displaying a single pronucleus at the zygote stage.
METHODS: Eighty-eight embryos from single pronucleus (1PN) two polar bodies (2PB)
ICSI zygotes from 64 preimplantational genetic screening (PGS) cycles (October
2012-December 2014), were retrospectively analyzed. Zygotes were cultured in a
time-lapse incubator. Embryo biopsy was performed on day 3 and genetic analysis
approached by array comparative genomic hybridization. RESULTS: Chromosomal
analysis revealed that 17% (15/88) of embryos derived from 1PN 2PB zygotes were
diagnosed as euploid. After blastomere biopsy at day 3, the blastocyst rate at
day 5 was 3.4% (3/88). Only 2.3% (2/88) euploid blastocysts were obtained. In two
couples and after counseling and patient agreement, the transfer of a euploid
blastocyst from a 1PN 2PB ICSI zygote was performed resulting in the birth of a
healthy child. CONCLUSIONS: These results open the possibility to consider
embryos coming from 1PN 2PB ICSI zygotes for transfer when no other embryos from
2PN 2PB ICSI zygotes are available and if a PGS diagnosis of euploidy is
obtained. Confirmation of biparental inheritance is strongly recommended.
PMID- 28497411
TI - Research amongst Irish surgical trainees: what's the trend?
AB - INTRODUCTION: A high publication rate for surgical trainees is considered a
prerequisite for progression to Higher Specialist Training (HST). This rate has
arguably been decreased by the formation of a new 'run-through' training pathway.
We aim to quantify the number of publications that the 'new' pathway trainees
have attained compared to the 'old' pathway trainees. We further aim to compare
the H-index and average citations between General Surgery (GS) and Trauma and
Orthopaedic (T&O) trainees. METHODS: Publications from old pathway trainee years
2007-2014 (T&O n = 59, GS n = 64) were compared with new pathway trainees from
2015 to 2016 (T&O n = 11, GS n = 12). H-index and average citations were also
compared for trainees commencing HST years 2007-2009. Statistical analysis
involved D'Agostino normality testing. An unpaired Student's t test +/- Welch's
correction was utilised for parametric data and a Mann-Whitney U test for non
parametric data. RESULTS: The average number of publications attained by the old
pathway T&O trainee was 4.2 +/- 3.1 and was 3.1 +/- 2.4 for the new trainee. Old
GS trainees had an average of 6.5 +/- 3.3 publications prior to HST with new GS
trainees having an average of 3.7 +/- 2.8 publications. The average H-index
attained for GS trainees on completion of the HST pathway was 5.1 +/- 3.2 and 4.6
+/- 2.4 for T&O trainees. CONCLUSION: There has been a significant decrease in
publication rates between new and old GS pathways. No significant changes were
identified between new and old T&O pathways. There was no difference between H
index and average citations between specialties.
PMID- 28497413
TI - Physician Perspectives on Readmissions.
PMID- 28497412
TI - Improved mortality outcomes over time for weekend emergency medical admissions.
AB - BACKGROUND: Multiple studies have suggested an association between weekend
hospital admissions and mortality. These have been limited by potential residual
confounders and a lack of explanation of causation. AIM: We previously attributed
adverse weekend outcomes to higher acuity; we have re-examined this question for
all emergency medical admissions to our institution from 2002 to 2014. METHODS:
We divided admissions by a weekday or weekend (Friday to Sunday) hospital
arrival. We utilised a multivariate logistic regression model, to determine
whether the latter was independently predictive of 30-day in-hospital mortality.
RESULTS: There were 82,368 admissions in 44,628 patients over the 13-year period.
Of admissions, 37.4% occurred at the weekend. The Acute Illness Severity Score,
the Charlson Co-morbidity Index and the Chronic Disabling Disease Score were
similar by a weekday or weekend admission. The multivariable logistic regression
showed no increase in 30-day in-hospital mortality for weekend admissions, odds
ratio 1.07 (95% confidence interval 0.98 to 1.16) (p = 0.11). Since the inception
of the AMAU, the per patient mortality for a weekend admission has declined from
13.5% in 2002 to 4.4% in 2014. This represents a relative risk reduction of 67.9%
with a number needed to treat of 10.8. Outcomes improved similarly for weekday
and weekend admissions. CONCLUSION: No increase in 30-day in-hospital mortality
for weekend admissions was found in this study. There has been a substantial
reduction in mortality for both weekday and weekend admissions over time.
PMID- 28497414
TI - Interprofessional Health Sciences Education: It's Time to Overcome Barriers and
Excuses.
PMID- 28497415
TI - Capsule Commentary on Ivlev et al., Use of Patient Decision Aids Increased
Younger Women's Reluctance to Begin Screening Mammography: A Systematic Review
and Meta-Analysis.
PMID- 28497416
TI - Internal Medicine Point-of-Care Ultrasound Curriculum: Consensus Recommendations
from the Canadian Internal Medicine Ultrasound (CIMUS) Group.
AB - Bedside point-of-care ultrasound (POCUS) is increasingly used to assess medical
patients. At present, no consensus exists for what POCUS curriculum is
appropriate for internal medicine residency training programs. This document
details the consensus-based recommendations by the Canadian Internal Medicine
Ultrasound (CIMUS) group, comprising 39 members, representing 14 institutions
across Canada. Guiding principles for selecting curricular content were
determined a priori. Consensus was defined as agreement by at least 80% of the
members on POCUS applications deemed appropriate for teaching and assessment of
trainees in the core (internal medicine postgraduate years [PGY] 1-3) and
expanded (general internal medicine PGY 4-5) training programs. We recommend four
POCUS applications for the core PGY 1-3 curriculum (inferior vena cava, lung B
lines, pleural effusion, and abdominal free fluid) and three ultrasound-guided
procedures (central venous catheterization, thoracentesis, and paracentesis). For
the expanded PGY 4-5 curriculum, we recommend an additional seven applications
(internal jugular vein, lung consolidation, pneumothorax, knee effusion, gross
left ventricular systolic function, pericardial effusion, and right ventricular
strain) and four ultrasound-guided procedures (knee arthrocentesis, arterial line
insertion, arterial blood gas sampling, and peripheral venous catheterization).
These recommendations will provide a framework for training programs at a
national level.
PMID- 28497418
TI - Assessing time-of-flight signal-to-noise ratio gains within the myocardium and
subsequent reductions in administered activity in cardiac PET studies.
AB - BACKGROUND: Time-of-flight (TOF) is known to increase signal-to-noise ratio (SNR)
and facilitate reductions in administered activity. Established measures of SNR
gain are derived from areas of uniform uptake, which is not applicable to the
heterogeneous uptake in cardiac PET images using fluoro-deoxyglucose (FDG). This
study aimed to develop a technique to quantify SNR gains within the myocardium
due to TOF. METHODS: Reference TOF SNR gains were measured in 88 FDG oncology
patients. Phantom data were used to translate reference SNR gains and validate a
method of quantifying SNR gains within the myocardium from parametric images
produced from multiple replicate images. This technique was applied to 13 FDG
cardiac viability patients. RESULTS: Reference TOF SNR gains of +23% +/- 8.5%
were measured in oncology patients. Measurements of SNR gain from the phantom
data were in agreement and showed the parametric image technique to be
sufficiently robust. SNR gains within the myocardium in the viability patients
were +21% +/- 2.8%. CONCLUSION: A method to quantify SNR gains from TOF within
the myocardium has been developed and evaluated. SNR gains within the myocardium
are comparable to those observed by established methods. This allows guidance for
protocol optimization for TOF systems in cardiac PET.
PMID- 28497417
TI - Purinergic P2X7 receptor functional genetic polymorphisms are associated with the
susceptibility to osteoporosis in Chinese postmenopausal women.
AB - Osteoporosis (OP) is a major public health problem worldwide. Genetic factors are
considered to be major contributors to the pathogenesis of OP. The purinergic
P2X7 receptor (P2X7R) has been shown to play a role in the regulation of
osteoblast and osteoclast activity and has been considered as an important
candidate gene for OP. A case-control study was performed to investigate the
associations of functional single nucleotide polymorphisms (SNPs) in the P2X7R
gene (rs2393799, rs7958311, rs1718119, rs2230911, and rs3751143) with
susceptibility to OP in 400 Chinese OP patients and 400 controls. Results showed
that rs3751143 was associated with OP; in particular, carriers of the C allele
and CC/(AC + CC) genotypes were at a higher risk of OP, but no significant
association of rs2230911, rs7958311, rs1718119, and rs2393799 with OP risk was
observed. Analysis of the haplotypes revealed one haplotype (rs1718119G
rs2230911G-rs3751143C) that appeared to be a significant "risk" haplotype with
OP. The rs3751143 polymorphism was associated with osteoclast apoptosis; ATP
induced caspase-1 activity of osteoclasts with AC and CC genotypes is lower than
that of osteoclasts with AA genotype in vitro. The findings suggest that the
P2X7R rs3751143 functional polymorphism might contribute to OP susceptibility in
Chinese postmenopausal women.
PMID- 28497419
TI - Gender Differences in the Presentation of Observable Risk Indicators of Problem
Gambling.
AB - In many countries where gambling is legalised, there has been a strong public
policy focus on the need for strategies to reduce gambling related harm. These
have often included policies requiring staff in gambling venues to identify
and/or assist people who might be experiencing gambling-related harm. To
facilitate this process, researchers have developed visible behavioural
indicators that might be used to profile potentially problematic gambling. Few of
these studies have, however, examined whether such indicators or 'warning signs'
might differ between men and women. In this study, we describe the results of an
analysis of data drawn from 1185 fortnightly gamblers that included 338 problem
gamblers as classified by the Problem Gambling Severity Index. Indicators of
problem gambling were similar between males and females with a few key
exceptions. Indicators reflecting emotional distress were more commonly reported
by females with gambling problems, whereas problem gambling males were more
likely to display aggressive behaviour towards gambling devices and others in the
venue. Amongst males, signs of emotional distress as well as attempts to conceal
their presence in venues from others most strongly differentiated between problem
and non-problem gamblers. Amongst females, signs of anger, a decline in grooming
and those attempts to access credit were the most distinguishing indicators.
These findings have implications for the refinement of identification policies
and practices.
PMID- 28497420
TI - The role of high airway pressure and dynamic strain on ventilator-induced lung
injury in a heterogeneous acute lung injury model.
AB - BACKGROUND: Acute respiratory distress syndrome causes a heterogeneous lung
injury with normal and acutely injured lung tissue in the same lung. Improperly
adjusted mechanical ventilation can exacerbate ARDS causing a secondary
ventilator-induced lung injury (VILI). We hypothesized that a peak airway
pressure of 40 cmH2O (static strain) alone would not cause additional injury in
either the normal or acutely injured lung tissue unless combined with high tidal
volume (dynamic strain). METHODS: Pigs were anesthetized, and heterogeneous acute
lung injury (ALI) was created by Tween instillation via a bronchoscope to both
diaphragmatic lung lobes. Tissue in all other lobes was normal. Airway pressure
release ventilation was used to precisely regulate time and pressure at both
inspiration and expiration. Animals were separated into two groups: (1) over
distension + high dynamic strain (OD + HDS, n = 6) and (2) over-distension + low
dynamic strain (OD + LDS, n = 6). OD was caused by setting the inspiratory
pressure at 40 cmH2O and dynamic strain was modified by changing the expiratory
duration, which varied the tidal volume. Animals were ventilated for 6 h
recording hemodynamics, lung function, and inflammatory mediators followed by an
extensive necropsy. RESULTS: In normal tissue (NT), OD + LDS caused minimal
histologic damage and a significant reduction in BALF total protein (p < 0.05)
and MMP-9 activity (p < 0.05), as compared with OD + HDS. In acutely injured
tissue (ALIT), OD + LDS resulted in reduced histologic injury and pulmonary edema
(p < 0.05), as compared with OD + HDS. CONCLUSIONS: Both NT and ALIT are
resistant to VILI caused by OD alone, but when combined with a HDS, significant
tissue injury develops.
PMID- 28497421
TI - Decreased miR-128 and increased miR-21 synergistically cause podocyte injury in
sepsis.
AB - OBJECTIVE: Glomerular podocytes are injured in sepsis. We studied, in a sepsis
patient, whether microRNAs (miRNAs) play a role in the podocyte injury. METHODS:
Podocytes were cultured and treated with lipopolysaccharide (LPS). Filtration
barrier function of podocyte was analyzed with albumin influx assay. Nephrin
level was analyzed with reverse transcription polymerase chain reaction (RT-PCR)
and western blot. MiRNAs were detected using miRNAs PCR Array and in situ
hybridization. MiRNA target sites were evaluated with luciferase reporter assays.
RESULTS: LPS impaired the filtration barrier function of podocytes. MiR-128 level
was decreased and miR-21 level was increased in podocytes in vitro and in the
sepsis patient. The decrease in miR-128 was sufficient to induce the loss of
nephrin and the impairment of filtration barrier function, while the increase of
miR-21 exacerbated the process. Snail and phosphatase and tensin homolog (PTEN)
were identified as the targets of miR-128 and miR-21. Decreased miR-128 induced
Snail expression, and the increased miR-21 stabilized Snail by regulating the
PTEN/Akt/GSK3beta pathway. Supplementation of miR-128 and inhibition of miR-21
suppressed Snail expression and prevented the podocyte injury induced by LPS.
CONCLUSION: Our study suggests that decreased miR-128 and increased miR-21
synergistically cause podocyte injury and are the potential therapeutic targets
in sepsis.
PMID- 28497422
TI - Utility of urinary circulating tumor DNA for EGFR mutation detection in different
stages of non-small cell lung cancer patients.
AB - PURPOSE: Non-invasive methods of molecular profiling for non-small cell lung
cancer (NSCLC) are useful for monitoring disease progression. The aim of the
current study was to ascertain if transrenal DNA is sensitive for clinical
correlation and EGFR detection in NSCLC patients. METHODS: 160 patients at
various stages of the disease participated and samples were collected
prospectively at 2-month intervals. A baseline sample was taken before treatment
commencement. To ascertain the sensitivity of transrenal DNA, we compared its
results with plasma DNA. ddPCR was used to profile the urine and blood samples
for key EGFR mutations. RESULTS: Using tumor tissues as references, our study
showed good concordance in EGFR mutations with transrenal DNA before treatment.
Results were highly matching in late-stage NSCLC patients, with stage III/IV
patients yielding an agreement of more than 90%. The assay was also sensitive to
detect early-stage patients after surgical procedures. Profiles were highly
concordant with results derived from plasma DNA, demonstrating the specificity of
transrenal DNA assays. Serial monitoring of these patients showed stable
molecular signatures and correlated to different treatments. Survival analysis
showed good prognostic utility for late-stage patients with high transrenal DNA
variations and patients that acquired T790M mutation. CONCLUSION: The study
demonstrated the feasibility of using transrenal DNA in mutation profiling for
different stages of NSCLC patients. It highlights the importance of continual
monitoring and has potential clinical utility in the clinical management of
NSCLC.
PMID- 28497423
TI - Validation of the prognostic value of new sub-stages within the AJCC 8th edition
of non-small cell lung cancer.
AB - BACKGROUND: The 8th edition of the American Joint Committee on Cancer (AJCC)
staging system for non-small cell lung cancer (NSCLC) has been released. The
current study tried to validate the prognostic significance of the new system
among patients registered within the surveillance, epidemiology and end results
(SEER) database. METHODS: SEER database (2010-2013) has been accessed through
SEER*Stat program and AJCC 8th edition stages were reconstructed utilizing the
collaborative stage descriptions. Overall and lung cancer-specific survival
analyses according to both 7th and 8th editions were conducted through Kaplan
Meier analysis and multivariate analysis was conducted through a Cox proportional
hazard model. RESULTS: A total of 127,096 patients with NSCLC were identified in
the period from 2010 to 2013. For overall survival assessment according to the
8th edition, P values for all pair-wise comparisons among different stages were
significant (<0.0001) except for the comparisons between stage IB and IIA (P =
0.146); stage IIA and IIB (P = 0.165). For lung cancer-specific survival
according to the 8th edition, P values for all pair-wise comparisons among
different stages were significant (<0.001). Among patients with stage I disease,
multivariate analysis for factors affecting overall and lung cancer-specific
survival among patients with stage I disease was conducted. The following factors
were associated with worse overall and lung cancer-specific survival: age >=70
years, more advanced stage, male gender, squamous histology, no surgery and no
radiotherapy (P < 0.0001 for all factors). CONCLUSION: This SEER analysis
supports the prognostic significance of the added sub-stages described within
AJCC 8th edition stages I and III. Further work is needed to incorporate
molecular markers and personalize the future editions of the AJCC staging system.
PMID- 28497424
TI - Validation of SDM-Q-Doc Questionnaire to measure shared decision-making
physician's perspective in oncology practice.
AB - OBJECTIVE: The aim of this study was to analyze the psychometric properties of
the Shared Decision-Making Questionnaire-Physician version (SDM-Q-Doc) in a
sample of medical oncologists who provide adjuvant treatment to patients with non
metastatic resected cancer and the correlations between the total SDM-Q-Doc score
and physician satisfaction with the information provided. METHODS: Prospective,
observational and multicenter study in which 32 medical oncologists and 520
patients were recruited. The psychometric properties, dimensionality, and factor
structure of the SDM-Q-Doc were assessed. RESULTS: Exploratory factor analyses
suggested that the most likely solution was two-dimensional, with two correlated
factors: one factor regarding information and another one about treatment.
Confirmatory factor analysis based on cross-validation showed that the fitted two
dimensional solution provided the best fit to the data. Reliability analyses
revealed good accuracy for the derived scores, both total and sub-scale, with
estimates ranging from 0.81 to 0.89. The results revealed significant
correlations between the total SDM-Q-Doc score and physician satisfaction with
the information provided (p < 0.01); between information sub-scale scores (factor
1) and satisfaction (p < 0.01), and between treatment sub-scale scores (factor 2)
and satisfaction (p < 0.01). Medical oncologists of older age and those with more
years of experience showed more interest in the patient preferences (p = 0.026
and p = 0.020, respectively). Patient age negatively correlated with SDM
information (p < 0.01) and physicians appear to provide more information to young
patients. CONCLUSION: SDM-Q-Doc showed good psychometric properties and could be
a helpful tool that examines physician's perspective of SDM and as an indicator
of quality and satisfaction in patients with cancer.
PMID- 28497425
TI - The next frontier in critical care guidelines: rapid and trustworthy
recommendations.
PMID- 28497426
TI - A systematic review of vasopressor blood pressure targets in critically ill
adults with hypotension.
AB - PURPOSE: Clinicians must balance the risks from hypotension with the potential
adverse effects of vasopressors. Experts have recommended a mean arterial
pressure (MAP) target of at least 65 mmHg, and higher in older patients and in
patients with chronic hypertension or atherosclerosis. We conducted a systematic
review of randomized-controlled trials comparing higher vs lower blood pressure
targets for vasopressor therapy administered to hypotensive critically ill
patients. METHODS: We searched MEDLINE(r), EMBASETM, and the Cochrane Central
Register of Controlled Trials for studies of higher vs lower blood pressure
targets for vasopressor therapy in critically ill hypotensive adult patients. Two
reviewers independently assessed trial eligibility based on titles and abstracts,
and they then selected full-text reports. Outcomes, subgroups, and analyses were
prespecified. We used GRADE (Grading of Recommendations Assessment, Development
and Evaluation) to rate the overall confidence in the estimates of intervention
effects. RESULTS: Of 8001 citations, we retrieved 57 full-text articles and
ultimately included two randomized-controlled trials (894 patients). Higher blood
pressure targets were not associated with lower mortality (relative risk [RR],
1.05; 95% confidence interval [CI], 0.90 to 1.23; P = 0.54), and neither age (P =
0.17) nor chronic hypertension (P = 0.32) modified the overall effect.
Nevertheless, higher blood pressure targets were associated with a greater risk
of new-onset supraventricular cardiac arrhythmia (RR, 2.08; 95% CI, 1.28 to 3.38;
P < 0.01). CONCLUSION: Current evidence does not support a MAP target > 70 mmHg
in hypotensive critically ill adult patients requiring vasopressor therapy.
PMID- 28497427
TI - CCCS-SSAI WikiRecs Clinical Practice Guideline: vasopressor blood pressure
targets in critically ill adults with hypotension.
PMID- 28497429
TI - Pathogenesis and FDG-PET/CT findings of Epstein-Barr virus-related lymphoid
neoplasms.
AB - Epstein-Barr virus (EBV) is one of the most common viruses, infecting more than
90% of the adult population worldwide. EBV genome is detected in some lymphoid
neoplasms. Not only their histopathological subtypes, but also their backgrounds
and their clinical courses are variable. A number of B-cell lymphoproliferative
disorders associated with the immunocompromised state are related to EBV
infection. The incidences of these disorders have been increasing along with
generalization of organ transplantations and use of immunosuppressive treatments.
Furthermore, some EBV-positive lymphoma can also occur in immunocompetent
patients. While evaluating patients with generalized lymphadenopathy of unknown
cause by positron emission tomography/computed tomography with 2-deoxy-2
[18F]fluoro-D-glucose (FDG-PET/CT), the possibility of lymphoid neoplasms should
be considered in some patients, and a careful review of the background and
previous history of the patients is necessary. In this review article, we
describe the pathogenesis of EBV-related lymphoid neoplasms and then present FDG
PET/CT images of representative diseases. In addition, we also present a review
of other EBV-related diseases, such as infectious mononucleosis and
nasopharyngeal carcinoma.
PMID- 28497428
TI - CCCS-SSAI WikiRecs Clinical Practice Guideline: vasopressors in early traumatic
shock.
PMID- 28497430
TI - Erratum to: Comparative evaluation of the algorithms for parametric mapping of
the novel myocardial PET imaging agent 18F-FPTP.
PMID- 28497431
TI - Effect of catheter-based renal denervation on left ventricular function, mass and
(un)twist with two-dimensional speckle tracking echocardiography.
AB - BACKGROUND: Speckle tracking echocardiography (STE) is an echocardiography
modality that is able to measure left ventricular (LV) characteristics, including
rotation, strain and strain rate. Strain measures myocardial fibre contraction
and relaxation. This study aims to assess the effect of renal sympathetic
denervation (RDN) on functional myocardial parameters, including STE, and to
identify potential differences between responders and non-responders. METHODS:
The study population consisted of 31 consecutive patients undergoing RDN in the
context of treatment for resistant hypertension. Patients were included between
December 2012 and June 2014. Transthoracic echocardiography and speckle tracking
analysis was performed at baseline and at 6 months follow-up. RESULTS: The study
population consisted of 31 patients with treatment-resistant hypertension treated
with RDN (mean age 64 +/- 10 years, 15 men). The total study population could be
divided into responders (n = 19) and non-responders (n = 12) following RDN. RDN
reduced office blood pressure by 18.9 +/- 26.8/8.5 +/- 13.5 mmHg (p < 0.001). A
significant decrease was seen in LV posterior wall thickness (LVPWd) (0.47 +/-
1.0 mm; p = 0.020), without a significant change in the LV mass index (LVMI). In
the total cohort, only peak late diastolic filling velocity (A-wave velocity)
decreased significantly by 5.3 +/- 13.2 cm/s (p = 0.044) and peak untwisting
velocity decreased significantly by 14.5 +/- 28.9 degrees /s (p = 0.025).
CONCLUSION: RDN reduced blood pressure and significantly improved functional
myocardial parameters such as A-wave velocity and peak untwisting velocity in
patients with treatment-resistant hypertension, suggesting a potential beneficial
effect of RDN on myocardial mechanics.
PMID- 28497432
TI - Resistance Mechanisms in Hepatitis C Virus: implications for Direct-Acting
Antiviral Use.
AB - Multiple direct-acting antiviral (DAA)-based regimens are currently approved that
provide one or more interferon-free treatment options for hepatitis C virus (HCV)
genotypes (G) 1-6. The choice of a DAA regimen, duration of therapy, and use of
ribavirin depends on multiple viral and host factors, including HCV genotype, the
detection of resistance-associated amino acid (aa) substitutions (RASs), prior
treatment experience, and presence of cirrhosis. In regard to viral factors that
may guide the treatment choice, the most important is the infecting genotype
because a number of DAAs are genotype-designed. The potency and the genetic
barrier may also impact the choice of treatment. One important and debated
possible virologic factor that may negatively influence the response to DAAs is
the presence of baseline RASs. Baseline resistance testing is currently not
routinely considered or recommended for initiating HCV treatment, due to the
overall high response rates (sustained virological response >90%) obtained.
Exceptions are patients infected by HCV G1a when initiating treatment with
simeprevir and elbasvir/grazoprevir or in those with cirrhosis prior to
daclatasvir/sofosbuvir treatment because of natural polymorphisms demonstrated in
sites of resistance. On the basis of these observations, first-line strategies
should be optimized to overcome treatment failure due to HCV resistance.
PMID- 28497433
TI - Marine protected areas in Costa Rica: How do artisanal fishers respond?
AB - Costa Rica is considering expanding their marine protected areas (MPAs) to
conserve marine resources. Due to the importance of households' responses to an
MPA in defining the MPA's ecological and economic outcomes, this paper uses an
economic decision framework to interpret data from near-MPA household surveys to
inform this policy discussion. The model and data suggest that the impact of
expanding MPAs relies on levels of enforcement and on-shore wages. If larger near
shore MPAs can produce high wages through increased tourism, MPA expansions could
provide ecological benefits with low burdens to communities. Due to distance
costs and gear investments, however, MPAs farther off-shore may place high
burdens on off-shore fishers.
PMID- 28497434
TI - Thalassemia and hemoglobinopathies in an ethnic minority group in Central
Vietnam: implications to health burden and relationship between two ethnic
minority groups.
AB - Thalassemia is a genetic condition that can result in long and expensive
treatments, and severe thalassemia may lead to death if left untreated. Couples
contributing two genes for thalassemia place their children at particular risk
for severe thalassemia. Gene frequency of thalassemia varies in Vietnam, but
presents remarkably high levels among some ethnic minority groups. Limited
information about thalassemia frequency makes prevention and control of
thalassemia difficult. This study aimed to determine gene frequency of certain
types of thalassemia among 390 women of reproductive age of the Ta-Oi ethnic
minority. Hemoglobin and DNA analyses were carried out to diagnose thalassemia
and hemoglobinopathies. Of the total participants, 56.1% (95% CI = 51.1-61.1)
carried thalassemia genes. A remarkably high frequency of hemoglobin Constant
Spring (Hb CS) of 23.8% (95% CI = 19.7-28.4) was noted. The frequency of alpha+
thalassemia (-3.7 kb deletion) was 26.4% (95% CI = 22.1-31.1), while hemoglobin E
(Hb E) and hemoglobin Pakse (Hb Ps) were identified at frequencies of 14.6 (95%
CI = 11.2-18.5) and 2.6% (95% CI = 1.4-5.0), respectively. Further analysis of
alpha-globin gene haplotype revealed the same Hb CS haplotype (+ - M + + -) as of
the Co-Tu minority, a neighboring minority of the Ta-Oi, indicating that these
two minorities may share the same ancestors. This information will be helpful for
further studies in population genetics, as well as the development prevention and
control program in the region.
PMID- 28497435
TI - Genetic Dimension of Intervertebral Disc Degeneration: Polymorphism of Matrix
Metalloproteinase 1 and 3 in the North Iranian Population.
AB - AIM: The etiology of intervertebral disc degeneration is still vague and both
genetic and environmental factors are assumed as the main causes. One of the
proposed genetic factors is the polymorphism of matrix metalloproteinases (MMPs)
genes. The aim of this study was to explore the relationship between two
polymorphisms (MMP-1-755 T/G [rs498186] and MMP-3 A/C [rs632478]) and disc
degeneration. MATERIAL AND METHODS: We performed a case-control study on 130
cases with intervertebral disc degeneration confirmed by magnetic resonance
imaging (MRI) and 210 healthy individuals. The Schneiderman criterion was used to
determine the severity of the disc degeneration. Blood samples were collected
from the participants. The genotyping was performed by the polymerase chain
reaction-restriction fragment length polymorphism (PCR-RFLP) method. Odds ratios
and 95% CIs were determined as measures of the strength of association between
genotypes and disc degeneration. RESULTS: The most frequent intervertebral disc
degeneration was observed in age range of 31-40 years (43.2%). A significant
association was found between the MMP-3 polymorphism and disc degeneration (p <
0.001). The homozygote CC was associated with an increased risk of disc
degeneration compared with the AA genotype (OR=5.25; 95%CI=2.82-9.77, p < 0.001).
We did not find any significant association of the MMP-1 polymorphism with disc
degeneration (p=0.95). CONCLUSION: The MMP-3 [rs632478] polymorphism may
contribute to susceptibility to disc degeneration. To confirm our findings,
additional well-designed studies in diverse ethnic populations are required.
PMID- 28497437
TI - FDA Approves TCH Combination for HER2-Positive Early Breast Cancer.
PMID- 28497436
TI - Factors Related to the Development of Shunt-Dependent Hydrocephalus Following
Subarachnoid Hemorrhage in the Elderly.
AB - AIM: Surgical procedures for aneurysmal subarachnoid hemorrhage (SAH) are
increasing among the elderly as the population ages. Chronic shunt-dependent
hydrocephalus is a recognized complication of SAH. The aim of this study was to
identify predictive factors for the development of shunt-dependent hydrocephalus
among elderly patients with SAH. MATERIAL AND METHODS: We retrospectively studied
878 patients, including 275 patients ? 65 years old, with SAH treated between
2005 and 2015 to identify factors contributing to the development of shunt
dependent hydrocephalus. The relationships between shunt-dependent hydrocephalus
and the causative factors were analyzed using univariate and multivariate
analysis; the causative factors were based on the results of previous studies.
RESULTS: In the 878 patients with SAH, there was a significant difference in the
incidence of shunt-dependent hydrocephalus between patients < 65 years old and
those ? 65 years old (p=0.021). In the 275 patients ? 65 years old, the following
were associated with shunt-dependent hydrocephalus on univariate analysis: 1)
Hunt and Hess grade (p=0.005), 2) Fisher grade (p < 0.001), 3) intraventricular
hemorrhage (p < 0.001), 4) acute hydrocephalus (p=0.003), 5) aneurysm location
(p=0.001), and 6) external ventricular drain placement (p < 0.001). On
multivariate analysis, only 1) intraventricular hemorrhage (p < 0.001) and 2) a
ruptured aneurysm located in the distal posterior circulation (p=0.014) were
related to an increased risk for the development of shunt-dependent
hydrocephalus. CONCLUSION: Evaluating risk factors can help identify patients at
high risk of developing shunt-dependent hydrocephalus. Identifying these risk
factors may help neurosurgeons to provide optimal therapy and improve outcomes in
patients with SAH.
PMID- 28497438
TI - A qualitative comparison of ten tissue clearing techniques.
AB - The understanding of spatially complex biological systems is greatly aided by the
availability of high resolution information on their tissue architecture, as is
provided by optical sectioning microscopy like confocal and light sheet
microscopy. In addition, genetically encoded fluorescent reporter proteins reveal
tissue architecture without the need for staining procedures. Owing to opacity
caused by scattering and absorption, light microscopy in tissue is limited to
thin tissue layers of a few micrometers traditionally provided by histological
sections. Aiming to allow deeper imaging, during the last decade massive efforts
to develop tissue clearing protocols produced a flurry of novel clearing
techniques for whole organ visualization, now available to microscopists. In
particular, new tissue clearing methods were developed that avoid the use of
organic solvents, aiming to retain the integrity of genetically encoded
fluorescent proteins. So far, these methods have not been directly compared and
selection of the right technique can be a non-trivial task. Here, we have aimed
to compare different tissue clearing approaches side by side in a standardized
manner. We provide qualitative data on their clearing capability of mouse brain,
lung, heart, kidney and muscle, as well as embryos and fetuses at the
developmental stages E10.5, E12.5 and E15.5 and discuss possible applications.
PMID- 28497439
TI - [Barcelona Test for Intellectual Disability: a new instrument for the
neuropsychological assessment of adults with intellectual disability].
AB - INTRODUCTION: Neuropsychological assessment in individuals with intellectual
disability is of utmost importance in order to determine the cognitive deficits
underlying brain dysfunction and limiting intellectual functioning and adaptive
behavior. However, no neuropsychological batteries in Spanish language have been
created and validated for this population. AIM: To adapt the 'programa integrado
de exploracion neuropsicologica-test Barcelona' and to validate the new version,
the Barcelona Test for Intellectual Disability (TB-DI). To create normative data
for its clinical use. SUBJECTS AND METHODS: The original test was modified based
on data from a pilot sample of 65 individuals with intellectual disability. In
order to study the psychometric properties of the TB-DI, it was administered to a
sample of 170 individuals with intellectual disability and to a group of 60
individuals without it. The relevant variables for stratification of normative
data were determined by means of regression models. RESULTS: The TB-DI was
finally composed by 67 subtests grouped in eight cognitive domains and it showed
good psychometric properties. Normative data were created for five groups taking
into account intellectual disability level, age and acquired curricular
competence. These data were organized in percentiles in a way that allows the
creation of cognitive profiles in the clinical and experimental fields.
CONCLUSION: The TB-DI constitutes a tool of high applicability in the population
with intellectual disability. It shows adequate validity and reliability, and it
has good psychometric properties. The cognitive profiles obtained by the TB-DI
will provide valuable information for the treatment of adult adults with mild and
moderate intellectual disability.
PMID- 28497440
TI - [Treatment of relapsing-remitting multiple sclerosis with fingolimod in routine
clinical practice].
AB - INTRODUCTION: Fingolimod is a selective immunosuppressant that targets the S1P
receptor, and is indicated in the treatment of aggressive relapsing-remitting
multiple sclerosis (RRMS) and following treatment failure with first-order drugs.
AIM: To investigate the safety and effectiveness of fingolimod under the
conditions of routine clinical practice. PATIENTS AND METHODS: We conducted an
observational study with prospective follow-up of patients with RRMS who received
fingolimod from January 2011 until February 2014. Data assessed were the
annualised relapse rate (ARR), disability measured by the Expanded Disability
Status Scale (EDSS), magnetic resonance activity and the appearance of side
effects. RESULTS: Our sample consisted of 122 patients, 79.5% of them females and
with a mean age of 26.8 years. They were classified, according to the last
treatment received, as being: naive (aggressive RRMS; n = 17), previous treatment
failure (n = 67) and withdrawal of natalizumab due to risk of progressive
multifocal leukoencephalopathy (n = 38). After a mean follow-up of 29.9 +/- 15.9
months, the ARR and the appearance of new lesions with gadolinium enhancement
were reduced in both the naive and the previous treatment failure groups. There
were no differences between the various subgroups as regards the progression of
EDSS or the time elapsed until the first attack or treatment failure. The risk of
treatment failure is higher with a baseline EDSS > 3 (hazard ratio: 4.24; p =
0.001) and presence of IgM oligoclonal bands (hazard ratio: 2.45; p < 0.022).
CONCLUSIONS: Fingolimod is an effective and well-tolerated drug under conditions
of routine clinical practice. Having a baseline EDSS > 3 and IgM oligoclonal
bands is predictive of a poor response to fingolimod.
PMID- 28497441
TI - [Cryptogenic stroke in a young patient with heart disease and kidney failure].
AB - INTRODUCTION: Fabry's disease is an infrequent metabolic pathology linked to the
X chromosome which causes a wide variety of signs and symptoms. CASE REPORT: A 39
year-old male who was admitted to our stroke unit with right-side hemiparesis (1
+ 0) and dysarthria (1). The score on the National Institute of Health Stroke
Scale was 2. The patient presented angiokeratomas in both thighs. A computerised
axial tomography scan of the head showed left thalamic acute infarction. The
duplex scan of the supra-aortic trunks was normal, and the transcranial Doppler
reflected a generalised increase in the pulsatility indices. Transthoracic
echocardiography showed left ventricular hypertrophy and left atrial dilatation.
He was discharged five days later, with antiaggregating medication but
asymptomatic. The prolonged Holter-electrocardiogram recording showed paroxysmal
atrial fibrillation. One notable value in the urine analysis was microalbuminuria
of 281 mg/L. In view of the multi-organic involvement and the family history, a
study for Fabry's disease was performed. Activity of the enzyme alpha
galactosidase A was diminished, and the presence of a mutation in the GLA gene
was found. The patient's brother, who suffered from kidney failure and atrial
fibrillation, was positive for this mutation. The patient is on treatment with
agalsidase beta. CONCLUSIONS: Fabry's disease must be suspected in young males
with heart disease, stroke or peripheral neuropathy, skin lesions, kidney failure
and a history of cases in the family. Hormone replacement therapy must be
established at an early stage, as it can improve the prognosis.
PMID- 28497443
TI - [XXXIV Reunion Anual de la Sociedad Valenciana de Neurologia. Communications].
PMID- 28497442
TI - [Myths and evidence on the use of botulinum toxin: spasticity in adults and in
children with cerebral palsy].
AB - INTRODUCTION: Spasticity is a medical problem with a high incidence that
significantly impact on the quality of life of patients and their families. AIM:
To analyze and to answer different questions about the use of botulinum toxin
type A (BTA) in our clinical practice. DEVELOPMENT: A group of experts in
neurology develop a list of topics related with the use of BTA. Two big groups
were considered: spasticity in adults and in children with cerebral palsy. A
literature search at PubMed for English, French, and Spanish language articles
published up to June 2016 was performed. The manuscript was structured as a
questionnaire that includes those questions that, according to the panel opinion,
could generate more controversy or doubt. The initial draft was reviewed by the
expert panel members to allow for modifications, and after subsequent revisions
for achieving the highest degree of consensus, the final text was then validated.
Different questions about diverse aspects of spasticity in adults, such as
methods for evaluating spasticity, infiltration techniques, doses, number of
infiltration points, etc. Regarding spasticity in children with cerebral palsy,
the document included questions about minimum age of infiltration, methods of
analgesia, etc. CONCLUSIONS: This review is a tool for continuous training for
neurologist and rehabilitation specialist and residents of both specialties,
about different specific areas of the management of BTA.
PMID- 28497444
TI - [Lance-Adams syndrome after infective endocarditis].
PMID- 28497445
TI - [Value of molecular imaging to examine the brain].
PMID- 28497446
TI - The role of water-jet dissection in improving erectile function and urinary
continence after nerve-sparing prostatectomy.
AB - OBJECTIVES: The aim of this study was to assess erectile function (EF) and
urinary continence (UC) recovery after nerve-sparing retropubic radical
prostatectomy (NS-RRPE) and nerve-sparing laparoscopic radical prostatectomy (NS
LRPE) depending on the neurovascular bundle (NVB) dissection technique used.
METHODS: Twenty-four hour pad test was used to assess the degree of postoperative
UC 1, 6 and 12 months after the surgery. For the purpose of EF assessment,
International Index of Erectile Function-5 (IIEF-5) questionnaire was used. In
addition, EF recovery assessment included the time needed to achieve a successful
sexual intercourse with or without Inhibitors Phosphodiesterase 5 (IPDE5). A
successful sexual intercourse was defined as an ability to achieve a strong
erection enough for penetration and maintain erection for a long time, throughout
the intercourse. Assessment was performed before the surgery and 8 and 6 months
after the surgery. RESULTS: In the patient group with BNS + water jet dissection
(WJD), the IIEF-5 score was considerably higher 8 weeks after the surgery (by 2.8
points) (r = 0.02). In 6 months, the difference between the group become more
significant and reached 3.5 points (p = 0.01). Three months after urethral
catheter removal, majority (95%) of patients in the NS-RPE + WJD group had no
urinary incontinence (UI). For standard NS-RPE, that figure was 87%. Mild stress
UI was observed in 5% of patients after NS-RPE + WJD and in 13% of patients after
NS-RPE. Six months after urethral catheter removal, no significant differences in
UC assessment were observed in the two groups. CONCLUSIONS: The implementation of
WJD of NVB in clinical practice has made it possible to considerably improve the
quality of life for postoperative patients due to good outcomes in terms of early
UC and EF recovery.
PMID- 28497447
TI - Holmium laser enucleation of the prostate (HoLEP) for small, large and giant
prostatic hyperplasia: tips and tricks.
AB - INTRODUCTION: Holmium laser enucleation of the prostate (HoLEP) allows to treat
extremely large prostates (>200 cm3). The aim of the study was to compare the
efficiency of HoLEP for prostates of different sizes. METHODS: Four hundred and
fifty-nine patients were divided into three groups: group 1 included 278 patients
(<100 cm3); group 2 included 169 patients (100-200 cm3); group 3 included 12
patients (>200 cm3). RESULTS: The duration of enucleation in group 1 was 56.5 +/-
10.7 min; in group 2 was 96.4 +/- 24.9 min; in group 3 was 120.9 +/- 35 min. The
duration of morcellation in group 1 was 37.5 +/- 7.3 min; in group 2 was 63.3 +/-
11.2 min; in group 3 was 84.0 +/- 25.6 min. The enucleation efficiency in group 3
(1.70 g/min) was higher (p<0.05) than in group 1 (1.05 g/min) and group 2 (1.23
g/min). Morcelation efficiency was lower in groups 1 and 2 (1.58 and 1.87 g/min,
respectively) than in group 3 (2.45 g/min) (p<0.05).Follow-up period lasted 18
months. There were no significant differences (p>0.05) in International Prostate
Symptom Score, Qmax, quality of life and postvoid residual volume for 1, 3, 6, 12
and 18 months after surgery. CONCLUSIONS: HoLEP is a safe, highly efficacious and
a size-independent procedure.
PMID- 28497448
TI - Healing of spongiosus-cutaneous fistula with hyperbaric Oxygen Therapy (HBOT): a
case report.
AB - INTRODUCTION: We present a case of a spongiosus-cutaneous fistula in a 39-year
old man with recurrent episodes of cutaneous abscess in dorsal middle third penis
(5 * 3 cm) treated with Hyperbaric Oxygen Therapy (HBOT). CASE REPORT: After
emptying nodular abscess, the patient was noncompliant for further surgery.
Therefore, it was suggested the association between HBOT and antibiotic therapy.
HBOT is carried out in a hyperbaric room, where the internal pressure is
increased (compression phase) by entering compressed air up to 283.71 kPa in
about 10 minutes. Every HBOT cycle lasted 24 days in which the patient had been
taking Amoxicillin/Clavulanic Acid 875 mg/125 mg 3 tabs/day and
Sulfamethoxazole/Trimethoprim 160 mg/800 mg 2 tabs/day for 2 weeks. At the end of
the treatment, a penile magnetic resonance imaging and an ultrasonography were
executed and they evidenced a complete remission of the lesion. In the subsequent
22 months, there was no recurrence. CONCLUSIONS: Our results suggest that HBOT is
an effective treatment for chronic wounds, including a spongiosus-cutaneous
fistula of unknown cause, when used in combination with conventional standard
therapy or further interventions. At present time, the gold standard remains
surgery; nevertheless, our experience with HBOT may stimulate its use in clinical
trials.
PMID- 28497449
TI - Percutaneous US-guided renal cryoablation using 3D modeling.
AB - INTRODUCTION: The article describes the first experience of performing
percutaneous ultrasound (US)-guided cryoablation of renal tumor and assesses the
safety and short-term results of treatment. MATERIALS AND METHODS: Twelve
patients were subjected to US-guided cryoablation of renal tumor in 2015. The
tumor size in 11 patients was up to 3.0 cm (T1a); in one female patient, 4.5 cm
(T1b). Tumors were assessed according to the PADUA score. In eight patients, it
was 6-7 (low); in three patients, 8-9 (average); in one, 10 (high). All the
patients underwent US examination using a FlexFocus 800 apparatus with convex
abdominal transducers. Before surgery and 6 months later, all the patients
underwent renal Doppler US and contrast-enhanced computed tomography. RESULTS:
The average cryoablation time was 60 min. Seven operations were performed under
spinal anesthesia and five operations under local anesthesia. The follow-up
period lasted 8 months on average. According to the ultrasonography and Doppler
findings, after 6 months, the tumor (T1a) in 11 patients reduced in size by an
average of 7-8 mm and had no blood supply.T1b patient's mass size reduces from
4.5 to 3.7 cm; however, a 1.5 cm area with a high attenuation gradient of the
contrast medium was visualized. Later, the patient was subjected to laparoscopic
renal resection. Histological finding revealed clear-cell carcinoma. CONCLUSIONS:
We consider percutaneous US-guided cryoablation as a method of choice for
patients with stage T1a renal tumor localized on the posterior or lateral surface
in the inferior or middle segment without sinus involvement and PADUA <9.
PMID- 28497450
TI - The role of hemodialysis in treatment of acute acetic acid poisonings.
AB - INTRODUCTION: The aim of this study is to show the importance of hemodialysis as
an active method in treatment of acute acetic acid poisonings. Its main role is
to support the renal function during the state of the intoxication when patients
develop acute renal failure. METHODS: We analyzed data from a 10-year period, a
total of 71 patients who ingested acetic acid, either intentionally or
accidentally. Patients with a need of hemodialysis (HD) treatment underwent 3- to
4-hour HD sessions every day or every second day, according to clinical
assessment, as needed, until recovery of kidney function. RESULTS: In the period
between 2006 and 2015 at the university clinic for toxicology and urgent internal
medicine, we hospitalized 6,106 patients with different kinds of intoxication, of
which 1.162% ingested concentrated acetic acid; 47 patients were female and 24
were male. The minimal age of patients was 18 and the maximal 74 years. A total
of 28 (39.43%) of the patients developed acute renal failure and in 10 patients
(14.08%) we used hemodialysis as a part of the treatment. The maximum number of
performed sessions in one patient was five and the minimal number of performed
sessions in one patents was only one session. The use of heparin led to fatal
bleeding in 4 patients. The mortality rate was 7% and most of the cases resulted
in fatalities during the first 96 hours after ingestion. CONCLUSIONS: Acetic acid
poisonings are one of the most dangerous intoxications seen in clinical
toxicology. The use of hemodialysis in some of the patients who develop acute
renal failure can be of great importance and it should be put into official
treatment protocols due to its great number of advantages in renal function
support.
PMID- 28497451
TI - Anterior greater trochanteric muscle pedicle bone grafting: a viable graft option
adjunct to hip osteotomy or fracture surgery.
AB - INTRODUCTION: The objectives were to evaluate a technique, outcome and
complications following anterior greater trochanteric with gluteus medius muscle
pedicle bone graft (AMG) procedure in the treatment of adolescent and active
adult hip disorders. METHODS: 20 patients (20 hips) with a mean age of 22.7 +/-
15.6 (range 10.0-63.5) years who had undergone AMG and been followed up more than
12 months postoperative were retrospectively enrolled in our study. The AMG
procedure was performed in conjunction with subcapital osteotomy for slipped
capital femoral epiphysis in 12 and open reduction for fracture/dislocation in 8
hips. At the most recent evaluation, patient functional status was rated by the
Harris Hip Score (HHS) and radiographic changes were graded according to Tonnis
criteria. Complications were defined as Tonnis grade >2 or hip requiring further
surgery. Univariate analysis was used to explore factors associated with
complications. Spearman's rank correlation coefficient was calculated between HHS
and Tonnis grading. RESULTS: At mean follow-up of 4.4 +/- 2.6 (range 1.1-9.5)
years, mean HHS was 87.4. Tonnis grading was rated as 0 in 10 hips, 1 in 5 hips,
2 in 2 hips, and 3 in 3 hips. Avascular necrosis of the femoral head as a
complication developed in 3 hips (15%). Clinical parameters including age at
surgery, duration of follow-up and diagnosis were not significantly associated
with postoperative complications. A negative correlation between HHS and Tonnis
grade was shown by Spearman's rank correlation (rs = -0.49, p = 0.03).
CONCLUSIONS: The AMG can be safely recommended as an adjunct bone graft procedure
when performing anterior open reduction of adolescent and active adult hip
disorders.
PMID- 28497452
TI - An attempt to throw light on congenital hip disease terminology and anticipation
of clinical outcomes when treated with total hip arthroplasty.
AB - The terminology of the wide spectrum of hip deformities seen during the neonatal,
infantile and adult life period remains controversial, mainly due to the
indiscriminate use of the terms dysplasia, subluxation, congenital hip disease,
developmental hip disease, congenital dislocation, etc. This has a serious
implication on the anticipation of clinical outcomes, complications and
comparison of different reconstructive techniques when these patients are treated
with total hip arthroplasty in adulthood. Journals, specialising in this field,
should publish homogeneous series (type of the disease, reconstruction technique,
implants) in order to clarify arguments and anticipate clinical outcomes.
PMID- 28497453
TI - Trends in total hip arthroplasty in young patients - results from a regional
register.
AB - INTRODUCTION: In the United Kingdom, over 83,000 primary total hip arthroplasties
(THAs) were performed last year, of which 20% are in patients under the age of 60
years. These patients generally have a longer life expectancy and a higher
activity level than an older cohort, which may potentially translate to higher
revision rates. METHODS: We reviewed our Trent regional arthroplasty register to
assess current surgical practice in younger patients undergoing total hip
arthroplasty. The results were compared to a previous study published in 2005.
RESULTS: Between 2010 and 2012, 1,097 primary THAs were performed on patients
aged 54 or less. There was an equal cohort of males to females with a mean age of
46 years of patients undergoing THA. Osteoarthritis was the commonest aetiology
for patients having surgery. Reviewing the components used there were 32
different femoral and 30 different acetabular types along with 70 different
combinations of components. There were 608 uncemented THAs, 313 hybrid THRs, 98
cemented THAs, 67 resurfacing arthroplasties and 11 reverse hybrid THAs.
DISCUSSION: The majority of implants were uncemented in both femur and acetabulum
with consultants performing most of the procedures. There is a clear preference
for uncemented femoral and acetabular fixation in the younger patient, and the
trend towards uncemented components has increased over the last 10 years amongst
the same surgeons. There continues to be a wide variety of cup and stem usage
along with many different combinations of components, with no consensus on the
ideal combination.
PMID- 28497454
TI - Efficacy of core decompression for treatment of canine femoral head osteonecrosis
induced by arterial ischaemia and venous congestion.
AB - METHODS: 40 healthy mixed-breed dogs were randomly divided into 2 groups,
arterial ischaemia (AI) and venous congestion (VC), each containing 20 dogs. The
dogs underwent a procedure where the deep femoral artery or deep femoral vein was
ligated randomly on the left or right side to establish the femoral head
osteonecrosis model. 13 dogs from each group, AI and VC, were randomly selected
for subsequent study. 3 dogs were randomly chosen from each group to receive core
decompression (CD) every 2 weeks for a total of 4 sessions. RESULTS: The
development of femoral head osteonecrosis was slightly slowed at each measurement
time point after CD in the arterial ischaemia (AI) group, but no restoration was
observed. The venous congestion (VC) group showed a gradually reduced mixed
signal after CD and exhibited a trend towards restoration. The various VC
subgroups had significantly improved symptoms compared to the AI subgroups.
CONCLUSIONS: CD displayed greater treatment efficacy for femoral head
osteonecrosis caused by VC, but poor efficacy for femoral head osteonecrosis
caused by AI.
PMID- 28497455
TI - Hip sonography: background; technique and common mistakes; results; debate and
politics; challenges.
AB - Developmental dysplasia of the hip (DDH) is the commonest 'congenital' disease of
the locomotor system throughout the world. According to the World Health
Organisation (WHO) Bone & Joint Decade (2000-2010) 10%-15% of patients who are
under the age of 50 when they require a hip replacement do so because of infant
hip dysplasia.The background; technique and common mistakes; results; debate and
politics; and the challenges of infant hip sonography are reviewed.
PMID- 28497456
TI - Survivorship and complications of total hip arthroplasty in patients with
dwarfism.
AB - BACKGROUND: Total hip arthroplasty (THA) is a common procedure used to treat bony
hip deformities and skeletal dysplasia in dwarfism. These surgeries are often
more difficult than conventional THA as they may involve malformed joints and
poor bone quality, and may require smaller prostheses. This study aims to
investigate whether implant survivorship and revision rates vary among patients
with and without dwarfism undergoing THA. METHODS: A retrospective case-control
study was performed for 102 THAs completed between 1997 and 2014 in patients
under the height threshold of 147.32 cm. This cohort was matched 1:1.5 with
patients of normal height with respect to age, gender, year of surgery, and
Charlson comorbidities. All cases had a minimum follow-up of 1 year. A chart
review was performed to identify patient and surgical characteristics, including
outcomes. Radiographs were assessed for deformity, loosening, and periprosthetic
fractures among other factors. RESULTS: The 2-, 5-, and 10-year survivorship of
THA in patients with dwarfism was 92.9%, 92.9%, and 80.7%, respectively; and
94.4%, 86.4%, and 86.4% for controls, respectively (p = 0.95). The dwarfism
cohort demonstrated an OR of 3.81 and 3.02 for revision for periprosthetic
fractures (p = 0.11) and mechanical wear (p = 0.21), respectively. CONCLUSIONS:
THA in patients with dwarfism achieves comparable results to a non-dwarfism
population with regards to implant survivorship; however, there is a trend toward
increased periprosthetic fractures and wear-related failures. Surgeons should be
aware of this potentially higher risk in this population and take morphological
differences into account during surgical planning and technique.
PMID- 28497457
TI - Mitochondrial DNA copy number variation as a potential predictor of renal cell
carcinoma.
AB - BACKGROUND: Peripheral blood mitochondrial DNA (mtDNA) copy number alteration has
been suggested as a risk factor for several types of cancer. The aim of the
present study was to assess the role of peripheral blood mtDNA copy number
variation as a noninvasive biomarker in the prediction and early detection of
renal cell carcinoma (RCC) in a cohort of Egyptian patients. METHODS:
Quantitative real-time polymerase chain reaction (qPCR) was used to measure
peripheral blood mtDNA copy numbers in 57 patients with newly diagnosed, early
stage localized RCC and 60 age- and sex-matched healthy individuals as a control
group. RESULTS: Median mtDNA copy number was significantly higher in RCC cases
than in controls (166 vs. 91, p<0.001). Increased mtDNA copy number was
associated with an 18-fold increased risk of RCC (95% confidence interval: 5.065
63.9). On receiver operating characteristic curve analysis, it was found that
mtDNA could distinguish between RCC patients and healthy controls, with 86%
sensitivity, 80% specificity, 80.3% positive predictive value and 85.7% negative
predictive value at a cutoff value of 108.5. CONCLUSIONS: Our results showed that
increased peripheral blood mtDNA copy number was associated with increased risk
of RCC. Therefore, RCC might be considered as part of a range of potential tumors
in cases with elevated blood mtDNA copy number.
PMID- 28497458
TI - Ocular Surface Disease in Patients under Topical Treatment for Glaucoma.
AB - PURPOSE: To examine the relationship between ocular surface disease (OSD) and
topical antiglaucoma therapy. METHODS: A total of 211 eyes of 211 patients with
open-angle glaucoma or ocular hypertension on topical medication were recruited
over 10 months. Controls were 51 eyes of 51 healthy age- and sex-matched
volunteers. In each patient, we recorded the intraocular pressure-lowering
eyedrops used, the number of medications used, and daily and cumulative
preservative concentrations (PC). Main outcome measures were fluorescein corneal
staining score (Oxford scale), lower tear meniscus height (LTMH) (spectral-domain
optical coherence tomography), noninvasive tear film breakup time (NI-TBUT)
(Oculus Keratograph 5M), and OSD symptom questionnaire index (OSDI). RESULTS:
Compared to controls, significantly higher OSDI (median [interquartile range]
10.24 [4.54-18.94] vs 2.5 [0-12.5]; p<0.001) and corneal staining (>=1: 64.93% vs
32.61%; p<0.001) scores were recorded in the medication group. The NI-TBUT and
LTMH failed to vary between the groups (p>0.05). A higher daily PC was associated
with a lower LTMH (R -0.142; p = 0.043). In the medication group, multivariate
analysis identified correlations between benzalkonium chloride (BAK) (odds ratio
[OR] 1.56) and BAK plus polyquaternium-containing drops (OR 5.09) or higher OSDI
(OR 1.06) and abnormal corneal staining test results and between older age (mean
ratio [MR] 1.05), longer treatment duration (MR 1.02), or corneal staining
presence (MR 1.22) and a higher OSDI score. CONCLUSIONS: Ocular surface disease
was more prevalent in the medication group. The main factors impacting OSD were
drops with preservatives, longer treatment duration, and older age.
PMID- 28497459
TI - Author's reply to comments to: Visual and anatomic outcomes after conversion to
aflibercept in neovascular age-related macular degeneration: 12-month results.
PMID- 28497460
TI - On the QT-interval and death from chloroform.
PMID- 28497461
TI - ICSI outcome in patients with high DNA fragmentation: Testicular versus
ejaculated spermatozoa.
AB - Sperm DNA fragmentation (SDF) has emerged as an important biomarker in the
assessment of male fertility potential with contradictory results regarding its
effect on ICSI. The aim of this study was to evaluate intracytoplasmic sperm
injection (ICSI) outcomes in male patients with high SDF using testicular versus
ejaculated spermatozoa. This is a prospective study on 36 men with high-SDF
levels who had a previous ICSI cycle from their ejaculates. A subsequent ICSI
cycle was performed using spermatozoa retrieved through testicular sperm
aspiration. Results of the prior ejaculate ICSI were compared with those of the
TESA-ICSI. The mean (SD) SDF level was 56.36% (15.3%). Overall, there was no
difference in the fertilization rate and embryo grading using ejaculate and
testicular spermatozoa (46.4% vs. 47.8%, 50.2% vs. 53.4% respectively). However,
clinical pregnancy was significantly higher in TESA group compared to ejaculated
group (38.89% [14 of 36] vs. 13.8% [five of 36]). Moreover, 17 live births were
documented in TESA group, and only three live births were documented in ejaculate
group (p < .0001). We concluded that the use of testicular spermatozoa for ICSI
significantly increases clinical pregnancy rate as well as live-birth rate in
patients with high SDF.
PMID- 28497462
TI - Skin hyperpigmentation following intravenous polymyxin B treatment associated
with melanocyte activation and inflammatory process.
AB - What is known and objective Polymyxins were widely used until the 1960s; however,
they fell into disfavour owing to their toxicity. The subsequent growth of
infections caused by multidrug-resistant Gram-negative bacteria has led to
renewed use of this class of antimicrobials in clinical practice. Acquired skin
hyperpigmentation (SH) following intravenous polymyxin B treatment has been
previously reported, but little is known about its pathogenesis, clinical course
and treatment. To improve understanding of these issues, we conducted a
prospective study of adult patients receiving intravenous polymyxin B treatment.
Methods Patients receiving intravenous polymyxin B treatment were followed
throughout the course of treatment. Clinical, dermatoscopic, histologic and
immunohistochemical skin properties of patients who presented with SH were
studied. Results and discussion Skin hyperpigmentation was noted in 8% of
patients (n=20/249); however, clinical, dermatoscopic, histologic and
immunohistochemical examinations were performed only in three patients for whom
the consent of relatives was obtained. Histologic and immunohistochemical
findings showed an abundant melanocyte-pigmented dendritic network. Langerhans
cells' hyperplasia and dermal IL-6 overexpression were also found, presumably for
an inflammatory process due to polymyxin B use. As polymyxin B causes the release
of histamine, which is known for its melanogenic effect, it is possible that skin
darkening is associated with this inflammatory mediator. What is new These
clinical and dermatoscopic findings contribute to a better understanding of how
the pigmentary reaction manifests following intravenous polymyxin B treatment.
Conclusion We concluded that hyperpigmentation due to intravenous polymyxin B
treatment is associated with an inflammatory process and subsequent melanocyte
activation. Although the pigmentary disorder neither influences the outcome of
the therapy nor warrants discontinuation of treatment, it nevertheless
considerably affects the patient's quality of life.
PMID- 28497463
TI - Can haematologic parameters be used for differential diagnosis of testicular
torsion and epididymitis?
AB - A differential diagnosis of testicular torsion and epididymitis has serious
importance for testicular health. In emergency conditions, if testicular torsion
goes unnoticed and epididymo-orchitis is diagnosed, organ loss may occur. This
study aimed to evaluate the usefulness of haematologic parameters for the
diagnosis of both testicular torsion and epididymo-orchitis and for differential
diagnosis of these two diseases. Patients were divided into three groups as those
undergoing surgery for testicular torsion, those receiving medical treatment for
epididymitis and a healthy control group. All patients had complete blood counts
taken with determinations of mean platelet volume (MPV), platelet/lymphocyte
ratio (PLR), neutrophil/lymphocyte ratio (NLR) and leucocyte counts. These were
then compared between groups. Leucocyte, MPV and NLR values were higher in both
the epididymitis and torsion groups compared to the controls (p < .001). Platelet
counts and PLR were significantly higher in the epididymitis group compared to
the other two groups (p < .001). Leucocyte, MPV and NLR values may be used in the
diagnosis of epididymitis and testicular torsion. Platelet counts and PLR appear
to be useful in differentiating epididymitis from testicular torsion. However,
there is a need for prospective studies with larger numbers of patients.
PMID- 28497464
TI - In vivo proton observed carbon edited (POCE) 13 C magnetic resonance spectroscopy
of the rat brain using a volumetric transmitter and receive-only surface coil on
the proton channel.
AB - PURPOSE: In vivo carbon-13 (13 C) MR spectroscopy (MRS) is capable of measuring
energy metabolism and neuroenergetics, noninvasively in the brain. Indirect (1 H
[13 C]) MRS provides sensitivity benefits compared with direct 13 C methods, and
normally includes a 1 H surface coil for both localization and signal reception.
The aim was to develop a coil platform with homogenous B1+ and use short
conventional pulses for short echo time proton observed carbon edited (POCE) MRS.
METHODS: A 1 H-[13 C] MRS coil platform was designed with a volumetric resonator
for 1 H transmit, and surface coils for 1 H reception and 13 C transmission. The
Rx-only 1 H surface coil nullifies the requirement for a T/R switch before the 1
H preamplifier; the highpass filter and preamplifier can be placed proximal to
the coil, thus minimizing sensitivity losses inherent with POCE-MRS systems
described in the literature. The coil platform was evaluated with a PRESS-POCE
sequence (TE = 12.6 ms) on a rat model. RESULTS: The coil provided excellent
localization, uniform spin nutation, and sensitivity. 13 C labeling of Glu-H4 and
Glx-H3 peaks, and the Glx-H2 peaks were observed approximately 13 and 21 min
following the infusion of 1-13 C glucose, respectively. CONCLUSION: A convenient
and sensitive platform to study energy metabolism and neurotransmitter cycling is
presented. Magn Reson Med 79:628-635, 2018. (c) 2017 International Society for
Magnetic Resonance in Medicine.
PMID- 28497465
TI - Designing 3D selective adiabatic radiofrequency pulses with single and parallel
transmission.
AB - PURPOSE: To introduce a method of designing single and parallel transmit (pTx) 3D
adiabatic pi pulses for inverting and refocusing spins that are insensitive to
transmit B1 ( B1+) inhomogeneity. THEORY AND METHODS: A 3D adiabatic pulse is
created by replacing each piece-wise constant element (or sub-pulse) of an
adiabatic full passage (AFP) by a 2D selective pulse. In this study, the parent
AFP is an HS1 and each sub-pulse is a 2D pulse derived from a jinc function
designed using a spiral k-trajectory. Spatial selectivity in the third direction
is achieved by blipping the slab-selective gradient between sub-pulses, yielding
a rectangular slab profile identical to that of the parent AFP. The slew-rate
limited sub-pulse can be undersampled utilizing pTx, thus shortening the overall
pulse width. Simulations and experiments demonstrate the quality of spatial
selectivity and adiabaticity achievable. RESULTS: The 3D adiabatic pulse inverts
and refocus spins in a sharply demarcated cylindrical volume. When stepping RF
amplitude, an adiabatic threshold is observed above which the flip angle remains
pi. Experimental results demonstrate that pTx is an effective means to
significantly improve pulse performance. CONCLUSION: A method of designing 3D
adiabatic pulses insensitive to B1 inhomogeneity has been developed. pTx can
shorten these pulses while retaining their adiabatic character. Magn Reson Med
79:701-710, 2018. (c) 2017 International Society for Magnetic Resonance in
Medicine.
PMID- 28497466
TI - Determination of inter-ionic and intra-ionic interactions in a monofluorinated
imidazolium ionic liquid by a combination of X-ray crystallography and NOE NMR
spectroscopy.
AB - We report the very first application of a Transient 1D 1 H{19 F} NOE NMR
experiment in neat ionic liquids. In comparison with classical 2D HOESY NMR
spectroscopy, a substantial reduction in measurement time is gained with
comparable quality and information content of the spectra. In combination with
classical X-ray crystallography, we have applied this technique for the
determination of inter-ionic distances (i.e. probabilities of presence) utilizing
an ionic liquid containing a monofluorinated imidazolium cation. Copyright (c)
2017 John Wiley & Sons, Ltd.
PMID- 28497467
TI - PhotoExam: adoption of an iOS-based clinical image capture application at Mayo
Clinic.
AB - BACKGROUND: Mayo Clinic developed an internal iOS-based, point-of-care clinical
image capture application for clinicians. We aimed to assess the adoption and
utilization of the application at Mayo Clinic. METHODS: Metadata of 22,784 photos
of 6417 patients taken by 606 users over 8040 clinical encounters between
3/1/2015 and 10/31/2015 were analyzed. A random sample of photos from 100
clinical encounters was assessed for quality using a five-item rubric. Use of
traditional medical photography services before and after application launch were
compared. RESULTS: The largest group of users was residents/fellows, accounting
for 31% of users but only 18% of all photos. Attending physicians accounted for
29% of users and 30% of photos. Nurses accounted for 14% of users and 28% of
photos. Surgical specialties had the most users (36% of users), followed by
dermatology (14% of users); however, dermatology accounted for 54% of all photos,
and surgery accounted for 26% of photos. Images received an average of 91% of
possible points on the quality scoring rubric. Most frequent reasons for missing
points were the location on the body not clearly being demonstrated (19% of
encounters) and the perspective/scale not being clearly demonstrated (12% of
encounters). There was no discernible pre-post effect of the application's launch
on use of traditional medical photography services. CONCLUSIONS: Point-of-care
clinical photography is a growing phenomenon with potential to become the new
standard of care. Patient and provider attitudes and the impact on patient
outcomes remain unclear.
PMID- 28497468
TI - A case-control study analyzing the association of keloids with hypertension and
obesity.
PMID- 28497470
TI - Cancer, ageing, multimorbidity and primary care.
AB - Cancer care is complex, and made more so by multimorbidity and ageing.
Multimorbidity affects all stages of cancer care from prevention and early
detection through to end of life care. The effectiveness of cancer treatments in
multimorbid patients may not be understood, as many conditions common in older
people may be exclusion criteria in oncology clinical trials. The interaction
between pre-existing physical capacity, multiple medical conditions and ageing
can delay diagnosis, impact on treatments, complicate survivor care, and impact
on decisions about starting and ceasing treatments. General Practitioners (GPs)
manages multimorbidity routinely, yet the GP role in comprehensive cancer care is
limited. Integration of GP management of multimorbidity in conjunction with
oncology services should improve patient outcomes. Integration of care for these
patients can educate patients on the minimisation of multimorbidity, develop
personalised screening plans and contribute to the wholistic management of people
in the surveillance period. GPs should have a major role in end of life care.
Integration of general practice and oncology should benefit patient care.
PMID- 28497469
TI - Prognostic models for identifying adults with intellectual disabilities and
mealtime support needs who are at greatest risk of respiratory infection and
emergency hospitalisation.
AB - BACKGROUND: Among adults with intellectual disabilities (ID), problems with
eating, drinking and swallowing (EDS), and an associated need for mealtime
support, are common, with an estimated 15% of adults known to specialist ID
services requiring mealtime support. We set out to identify which adults with ID
who receive mealtime support are at an increased risk of respiratory infections
and emergency hospitalisation related to EDS problems. METHOD: An exploratory,
prospective cohort study was undertaken in the East of England. At baseline,
structured interviews with the caregivers of 142 adults with ID and any type of
mealtime support needs were used to gather information on health and support
needs over the previous 12 months. These interviews were repeated at follow-up,
12 months later. The resulting dataset, covering a 24-month period, was analysed
with logistic regression, using model averaging to perform sensitivity analysis,
and backwards step-wise variable selection to identify the most important
predictors. RESULTS: Individuals with a history of respiratory infections (in the
first year of study), those who had epilepsy and those with caregiver-reported
difficulty swallowing were most likely to have respiratory infections in the
second year. Adults with increasing mealtime support needs, epilepsy and/or full
mealtime support needs (fed mainly or entirely by a caregiver or enterally) were
at increased risk of emergency hospitalisation for EDS-related problems.
CONCLUSIONS: Our findings highlight the importance of carefully monitoring health
issues experienced by adults with ID and EDS problems, as well as their eating,
drinking and swallowing skills. However, the models developed in this exploratory
research require validation through future studies addressing the EDS problems
commonly experienced by adults with ID and their implications for health outcomes
and quality of life. Further research into the relationship between epilepsy and
EDS problems would provide much-needed insight into the complex relationship
between the two areas.
PMID- 28497471
TI - Clinician perspectives on symptom and quality of life experiences of patients
during cancer therapies: Implications for eHealth.
AB - OBJECTIVE: The purpose of this study was to explore clinician experiences with
cancer symptom and quality of life (SQL) management from diagnosis throughout
therapy in the ambulatory setting, plus identify preferences for a future SQL
decision support system. METHODS: Eligible clinicians worked in ambulatory cancer
care with responsibility for direct patient care. Focus groups were conducted to
discuss symptom management throughout the treatment experience and features
desired in a future decision support system. Each group was audio-recorded,
transcribed, de-identified, and entered into NVivo 9 for analysis. Open and axial
coding was completed, grouping common concepts into nodes; large constructs among
the nodes were identified and main messages were synthesized. RESULTS: A total of
118 clinicians were contacted by email resulting in a final sample of 51
attending 1 of 9 focus groups. Clinicians described a standard face-to-face
approach to assessment of SQL, before and throughout therapy. Preparing patients
for expected symptoms and approaches to management included paper-based patient
education materials and referrals. Communicating with patients between visits was
covered in detail, notably use of telephone and email. Future system features
desired by the clinicians included an electronic, Web-based system with real
time, trended data, reasonable alerts, and tailored information for patients.
CONCLUSIONS: Cancer care specialists reported strategies to assess and manage
cancer SQL in ambulatory care including patient-reported outcome measures,
contact communication modes, face-to-face interviews, and paper-based patient
education materials. Future system features desired by clinicians included an
electronic, Web-based system with real-time, trended data, reasonable alerts, and
tailored information for patients.
PMID- 28497472
TI - Current knowledge on biomarkers for contact sensitization and allergic contact
dermatitis.
AB - Contact sensitization is common and affects up to 20% of the general population.
The clinical manifestation of contact sensitization is allergic contact
dermatitis. This is a clinical expression that is sometimes difficult to
distinguish from other types of dermatitis, for example irritant and atopic
dermatitis. Several studies have examined the pathogenesis and severity of
allergic contact dermatitis by measuring the absence or presence of various
biomarkers. In this review, we provide a non-systematic overview of biomarkers
that have been studied in allergic contact dermatitis. These include genetic
variations and mutations, inflammatory mediators, alarmins, proteases,
immunoproteomics, lipids, natural moisturizing factors, tight junctions, and
antimicrobial peptides. We conclude that, despite the enormous amount of data,
convincing specific biomarkers for allergic contact dermatitis are yet to be
described.
PMID- 28497473
TI - Topical analgesics for acute and chronic pain in adults - an overview of Cochrane
Reviews.
AB - BACKGROUND: Topical analgesic drugs are used for a variety of painful conditions.
Some are acute, typically strains or sprains, tendinopathy, or muscle aches.
Others are chronic, typically osteoarthritis of hand or knee, or neuropathic
pain. OBJECTIVES: To provide an overview of the analgesic efficacy and associated
adverse events of topical analgesics (primarily nonsteroidal anti-inflammatory
drugs (NSAIDs), salicylate rubefacients, capsaicin, and lidocaine) applied to
intact skin for the treatment of acute and chronic pain in adults. METHODS: We
identified systematic reviews in acute and chronic pain published to February
2017 in the Cochrane Database of Systematic Reviews (the Cochrane Library). The
primary outcome was at least 50% pain relief (participant-reported) at an
appropriate duration. We extracted the number needed to treat for one additional
beneficial outcome (NNT) for efficacy outcomes for each topical analgesic or
formulation, and the number needed to treat for one additional harmful outcome
(NNH) for adverse events. We also extracted information on withdrawals due to
lack of efficacy or adverse events, systemic and local adverse events, and
serious adverse events. We required information from at least 200 participants,
in at least two studies. We judged that there was potential for publication bias
if the addition of four studies of typical size (400 participants) with zero
effect increased NNT compared with placebo to 10 (minimal clinical utility). We
extracted GRADE assessment in the original papers, and made our own GRADE
assessment. MAIN RESULTS: Thirteen Cochrane Reviews (206 studies with around
30,700 participants) assessed the efficacy and harms from a range of topical
analgesics applied to intact skin in a number of acute and chronic painful
conditions. Reviews were overseen by several Review Groups, and concentrated on
evidence comparing topical analgesic with topical placebo; comparisons of topical
and oral analgesics were rare.For at least 50% pain relief, we considered
evidence was moderate or high quality for several therapies, based on the
underlying quality of studies and susceptibility to publication bias.In acute
musculoskeletal pain (strains and sprains) with assessment at about seven days,
therapies were diclofenac Emulgel (78% Emulgel, 20% placebo; 2 studies, 314
participants, NNT 1.8 (95% confidence interval 1.5 to 2.1)), ketoprofen gel (72%
ketoprofen, 33% placebo, 5 studies, 348 participants, NNT 2.5 (2.0 to 3.4)),
piroxicam gel (70% piroxicam, 47% placebo, 3 studies, 522 participants, NNT 4.4
(3.2 to 6.9)), diclofenac Flector plaster (63% Flector, 41% placebo, 4 studies,
1030 participants, NNT 4.7 (3.7 to 6.5)), and diclofenac other plaster (88%
diclofenac plaster, 57% placebo, 3 studies, 474 participants, NNT 3.2 (2.6 to
4.2)).In chronic musculoskeletal pain (mainly hand and knee osteoarthritis)
therapies were topical diclofenac preparations for less than six weeks (43%
diclofenac, 23% placebo, 5 studies, 732 participants, NNT 5.0 (3.7 to 7.4)),
ketoprofen over 6 to 12 weeks (63% ketoprofen, 48% placebo, 4 studies, 2573
participants, NNT 6.9 (5.4 to 9.3)), and topical diclofenac preparations over 6
to 12 weeks (60% diclofenac, 50% placebo, 4 studies, 2343 participants, NNT 9.8
(7.1 to 16)). In postherpetic neuralgia, topical high-concentration capsaicin had
moderate-quality evidence of limited efficacy (33% capsaicin, 24% placebo, 2
studies, 571 participants, NNT 11 (6.1 to 62)).We judged evidence of efficacy for
other therapies as low or very low quality. Limited evidence of efficacy,
potentially subject to publication bias, existed for topical preparations of
ibuprofen gels and creams, unspecified diclofenac formulations and diclofenac gel
other than Emulgel, indomethacin, and ketoprofen plaster in acute pain
conditions, and for salicylate rubefacients for chronic pain conditions. Evidence
for other interventions (other topical NSAIDs, topical salicylate in acute pain
conditions, low concentration capsaicin, lidocaine, clonidine for neuropathic
pain, and herbal remedies for any condition) was very low quality and typically
limited to single studies or comparisons with sparse data.We assessed the
evidence on withdrawals as moderate or very low quality, because of small numbers
of events. In chronic pain conditions lack of efficacy withdrawals were lower
with topical diclofenac (6%) than placebo (9%) (11 studies, 3455 participants,
number needed to treat to prevent (NNTp) 26, moderate-quality evidence), and
topical salicylate (2% vs 7% for placebo) (5 studies, 501 participants, NNTp 21,
very low-quality evidence). Adverse event withdrawals were higher with topical
capsaicin low-concentration (15%) than placebo (3%) (4 studies, 477 participants,
NNH 8, very low-quality evidence), topical salicylate (5% vs 1% for placebo) (7
studies, 735 participants, NNH 26, very low-quality evidence), and topical
diclofenac (5% vs 4% for placebo) (12 studies, 3552 participants, NNH 51, very
low-quality evidence).In acute pain, systemic or local adverse event rates with
topical NSAIDs (4.3%) were no greater than with topical placebo (4.6%) (42
studies, 6740 participants, high quality evidence). In chronic pain local adverse
events with topical capsaicin low concentration (63%) were higher than topical
placebo (5 studies, 557 participants, number needed to treat for harm (NNH) 2.6),
high quality evidence. Moderate-quality evidence indicated more local adverse
events than placebo in chronic pain conditions with topical diclofenac (NNH 16)
and local pain with topical capsaicin high-concentration (NNH 16). There was
moderate-quality evidence of no additional local adverse events with topical
ketoprofen over topical placebo in chronic pain. Serious adverse events were rare
(very low-quality evidence).GRADE assessments of moderate or low quality in some
of the reviews were considered by us to be very low because of small numbers of
participants and events. AUTHORS' CONCLUSIONS: There is good evidence that some
formulations of topical diclofenac and ketoprofen are useful in acute pain
conditions such as sprains or strains, with low (good) NNT values. There is a
strong message that the exact formulation used is critically important in acute
conditions, and that might also apply to other pain conditions. In chronic
musculoskeletal conditions with assessments over 6 to 12 weeks, topical
diclofenac and ketoprofen had limited efficacy in hand and knee osteoarthritis,
as did topical high-concentration capsaicin in postherpetic neuralgia. Though
NNTs were higher, this still indicates that a small proportion of people had good
pain relief.Use of GRADE in Cochrane Reviews with small numbers of participants
and events requires attention.
PMID- 28497474
TI - Single and multiple sevoflurane exposures during pregnancy and offspring behavior
in mice.
AB - BACKGROUND: The second trimester is a period of neurogenesis and neuronal
migration, which can be affected by exposure to anesthetics. Studies also suggest
that multiple exposures may have a greater impact on neurodevelopment. AIM: We
investigated whether in utero single or multiple exposures to anesthetics caused
long-term behavior changes. METHODS: Pregnant mice were randomly divided into
four groups on gestational day 14 (GD 14). Mice in the Control * 1 group were
exposed to 100% oxygen for 150 min. Mice in the Sevo * 1 group were also exposed
to 100% oxygen for 150 min, except that 2.5% sevoflurane was added during the
first 120 min. Mice in the Control * 3 and Sevo * 3 group were identically
treated as Control * 1 and Sevo * 1 group for three consecutive days,
respectively (GD 14-16). Behavioral tests were performed only with the male
offspring at the age of 2-4 months. Synaptic plasticity was also compared by
inducing long-term potentiation in acute hippocampal slices. RESULTS: Single or
multiple sevoflurane exposures in pregnant mice during the second trimester did
not cause long-lasting behavioral consequences or changes in long-term synaptic
plasticity of their offspring. CONCLUSION: Our study suggests that neither single
nor multiple exposures of mice to sevoflurane during the fetal developmental
period induces long-term behavioral dysfunctions or affects long-term synaptic
plasticity. Additional studies focusing on early stages of neurodevelopment are
necessary to confirm the effects of sevoflurane exposure during pregnancy.
PMID- 28497475
TI - Quality of life of primary caregivers of children with cerebral palsy: a
comparison between mother and grandmother caregivers in Anhui province of China.
AB - BACKGROUND: The aims of the study are to evaluate the quality of life of mother
and grandmother primary caregivers of children with cerebral palsy (CP) and to
compare the difference between these two groups of caregivers. METHODS: We
recruited 125 mother and 52 grandmother primary caregivers of children with CP.
All the primary caregivers were interviewed with the short-form 36 (SF-36) health
survey version 2.0 and with researcher-designed questionnaires for family
background. As for the children, social-demographic characteristics, medical
history and the result of a physical examination performed by a paediatric
specialist in neurological rehabilitation were also collected. RESULTS: Mother
and grandmother caregivers scored lower than their counterparts in the general
population in both summary scores. Grandmother caregivers had lower scores than
mother caregivers in all eight domains and in the two summary scores, with all
differences being statistically significant (P < 0.05), except for the domain of
the mental component summary score (P = 0.618). The differences were found
particularly remarkable in the domains of physical functioning, role physical,
bodily pain and also the physical component summary score (P < 0.001).
CONCLUSIONS: The quality of life is significantly unsatisfactory in both mother
and grandmother primary caregivers of children with CP; this research provides
evidence for the need of the monitoring of these caregivers.
PMID- 28497476
TI - Optimization of a novel large field of view distortion phantom for MR-only
treatment planning.
AB - PURPOSE: MR-only treatment planning requires images of high geometric fidelity,
particularly for large fields of view (FOV). However, the availability of large
FOV distortion phantoms with analysis software is currently limited. This work
sought to optimize a modular distortion phantom to accommodate multiple bore
configurations and implement distortion characterization in a widely
implementable solution. METHOD AND MATERIALS: To determine candidate materials,
1.0 T MR and CT images were acquired of twelve urethane foam samples of various
densities and strengths. Samples were precision-machined to accommodate 6 mm
diameter paintballs used as landmarks. Final material candidates were selected by
balancing strength, machinability, weight, and cost. Bore sizes and minimum
aperture width resulting from couch position were tabulated from the literature
(14 systems, 5 vendors). Bore geometry and couch position were simulated using
MATLAB to generate machine-specific models to optimize the phantom build.
Previously developed software for distortion characterization was modified for
several magnet geometries (1.0 T, 1.5 T, 3.0 T), compared against previously
published 1.0 T results, and integrated into the 3D Slicer application platform.
RESULTS: All foam samples provided sufficient MR image contrast with paintball
landmarks. Urethane foam (compressive strength ~1000 psi, density ~20 lb/ft3 )
was selected for its accurate machinability and weight characteristics. For
smaller bores, a phantom version with the following parameters was used: 15 foam
plates, 55 * 55 * 37.5 cm3 (L*W*H), 5,082 landmarks, and weight ~30 kg. To
accommodate > 70 cm wide bores, an extended build used 20 plates spanning 55 * 55
* 50 cm3 with 7,497 landmarks and weight ~44 kg. Distortion characterization
software was implemented as an external module into 3D Slicer's plugin framework
and results agreed with the literature. CONCLUSION: The design and implementation
of a modular, extendable distortion phantom was optimized for several bore
configurations. The phantom and analysis software will be available for multi
institutional collaborations and cross-validation trials to support MR-only
planning.
PMID- 28497477
TI - Fontan operation with bilateral conduits for the treatment of pulmonary
arteriovenous fistulas in a patient with polysplenia after reconstruction of a
non-confluent pulmonary artery.
AB - We describe a case involving a successful Fontan procedure for the treatment of
pulmonary arteriovenous fistulas in a patient with polysplenia. The patient was
diagnosed with bilateral superior vena cavae, interrupted inferior vena cava with
azygos connection, wide separate hepatic veins, and central pulmonary artery
stenosis following repair of a non-confluent pulmonary artery. Bilateral
extracardiac conduits were used to connect each hepatic vein to the pulmonary
artery, opposite each superior vena cava. Clinical improvement in the pulmonary
arteriovenous fistulas was observed within 4 months after surgery.
PMID- 28497478
TI - Comparison of the clinical efficacy and safety of the on-demand use of
paroxetine, dapoxetine, sildenafil and combined dapoxetine with sildenafil in
treatment of patients with premature ejaculation: A randomised placebo-controlled
clinical trial.
AB - The aim of the study was to compare the clinical efficacy and safety of the on
demand use of paroxetine, dapoxetine, sildenafil and combined dapoxetine with
sildenafil in treatment of patients with premature ejaculation (PE). In a single
blind placebo-controlled clinical study, 150 PE patients without erectile
dysfunction (ED) were included during the period of March 2015 to May 2016.
Patients were randomly divided into five groups (30 patients each). On demand
placebo, paroxetine (30 mg), dapoxetine (30 mg), sildenafil citrate (50 mg) and
combined dapoxetine (30 mg) with sildenafil citrate (50 mg) were given for
patients for 6 weeks in each group respectively. All patients were instructed to
record intravaginal ejaculatory latency time (IELT) and evaluated with Premature
Ejaculation Diagnostic Tool (PEDT) and the patient satisfaction score before and
after treatment. The mean of IELT, satisfaction score and PEDT in all groups was
significantly improved after treatment (p value = .001). Combined dapoxetine with
sildenafil group had the best values of IELT, satisfaction scores and PEDT in
comparison with other treatment groups (p value <.001). The combined dapoxetine
with sildenafil therapy could significantly improve PE patients without ED as
compared to paroxetine alone or dapoxetine alone or sildenafil alone with
tolerated adverse effects.
PMID- 28497479
TI - Proximate composition, amino acid and fatty acid profiles of marine snail Rapana
venosa meat, visceral mass and operculum.
AB - BACKGROUND: Rapana venosa (Rv), an important marine snail, demonstrates an
increasing nutritional and economic importance. However, there is still limited
information available on their nutritional composition. The present study
highlights and provides new information on the proximate composition, amino acid
and fatty acid profiles of different body parts of Rv, aiming for its better
application and research. RESULTS: The operculum contained a high amount of
protein and flavor amino acids. The edible tissues, including meat and visceral
mass, were valuable sources of essential amino acids (EAA) apart from methionine
and cysteine. In addition, the meat contained high amount of taurine. Fatty acid
analysis indicated that the edible tissues contained high amounts of omega3 fatty
acids, especially eicosapentaenoic acid (EPA) (C20:5omega3) and docosahexaenoic
acid (DHA) (C22:6omega3), and had a low omega6/omega3 fatty acid ratio.
Interestingly, significantly higher concentrations of most nutritional elements
such as fat, EAA, EPA and DHA, were found in the visceral mass compared to those
in the meat. CONCLUSION: The operculum of Rv may became a very interesting source
for some protein and flavor peptide development, and the edible parts of Rv may
be utilized for special dietary applications requiring high amounts of taurine,
EPA, DHA and a lower omega6/omega3 fatty acid ratio. (c) 2017 Society of Chemical
Industry.
PMID- 28497480
TI - Effectiveness of portable electronic and optical magnifiers for near vision
activities in low vision: a randomised crossover trial.
AB - PURPOSE: To compare the performance of near vision activities using additional
portable electronic vision enhancement systems (p-EVES), to using optical
magnifiers alone, by individuals with visual impairment. METHODS: A total of 100
experienced optical aid users were recruited from low vision clinics at
Manchester Royal Eye Hospital, Manchester, UK, to a prospective two-arm cross
over randomised controlled trial. Reading, performance of near vision activities,
and device usage were evaluated at baseline; and at the end of each study arm
(Intervention A: existing optical aids plus p-EVES; Intervention B: optical aids
only) which was after 2 and 4 months. RESULTS: A total of 82 participants
completed the study. Overall, maximum reading speed for high contrast sentences
was not statistically significantly different for optical aids and p-EVES,
although the critical print size and threshold print size which could be accessed
with p-EVES were statistically significantly smaller (p < 0.001 in both cases).
The optical aids were used for a larger number of tasks (p < 0.001), and used
more frequently (p < 0.001). However p-EVES were preferred for leisure reading by
70% of participants, and allowed longer duration of reading (p < 0.001). During
the study arm when they had a p-EVES device, participants were able to carry out
more tasks independently (p < 0.001), and reported less difficulty with a range
of near vision activities (p < 0.001). CONCLUSIONS: The study provides evidence
that p-EVES devices can play a useful role in supplementing the range of low
vision aids used to reduce activity limitation for near vision tasks.
PMID- 28497481
TI - Harnessing polarisation transfer to indazole and imidazole through signal
amplification by reversible exchange to improve their NMR detectability.
AB - The signal amplification by reversible exchange (SABRE) approach has been used to
hyperpolarise the substrates indazole and imidazole in the presence of the co
ligand acetonitrile through the action of the precataysts [IrCl(COD)(IMes)] and
[IrCl(COD)(SIMes)]. 2 H-labelled forms of these catalysts were also examined. Our
comparison of the two precatalysts [IrCl(COD)(IMes)] and [IrCl(COD)(SIMes)],
coupled with 2 H labelling of the N-heterocyclic carbene and associated
relaxation and polarisation field variation studies, demonstrates the critical
and collective role these parameters play in controlling the efficiency of signal
amplification by reversible exchange. Ultimately, with imidazole, a 700-fold1 H
signal gain per proton is produced at 400 MHz, whilst for indazole, a 90-fold
increase per proton is achieved. The co-ligand acetonitrile proved to optimally
exhibit a 190-fold signal gain per proton in these measurements, with the
associated studies revealing the importance the substrate plays in controlling
this value. Copyright (c) 2017 The Authors. Magnetic Resonance in Chemistry
published by John Wiley & Sons Ltd.
PMID- 28497482
TI - Quality changes and shelf-life extension of ready-to-eat fish patties by adding
encapsulated citric acid.
AB - BACKGROUND: Citric acid is commonly used as a flavoring and preservative in food
and beverages. The effect of adding citric acid directly or encapsulated (each at
1 and 2 g kg-1 ) on the quality and shelf-life of ready-to-eat sea bass patties
was evaluated during storage at 4 degrees C in vacuum skin packaging. RESULTS:
Microbial growth and total basic volatile nitrogen were maintained at relatively
low levels up to 8 weeks of storage. With respect to oxidative stability, the
addition of encapsulated citric acid minimized secondary oxidation values more
efficiently than its direct addition, regardless of the concentration. This is in
agreement with the decreased fishy odor observed in those patties containing
encapsulated citric acid. Accordingly, sensory analysis showed that the addition
of encapsulated citric acid at 1 g kg-1 resulted in lower scores in fish aroma
compared to that of the control. Sourness is dependent on the amount of citric
acid added, regardless of the form (direct or encapsulated). CONCLUSIONS: The
form of citric acid addition, rather than the amount of citric acid added, caused
changes in texture. Therefore, the use of encapsulated citric acid represents a
suitable strategy that is of great interest in the seafood industry. (c) 2017
Society of Chemical Industry.
PMID- 28497483
TI - Incentives to patients versus incentives to health care providers: The users'
perspective.
AB - In theory, health care providers may adapt their professional behavior to the
financial incentives resulting from their remuneration. Our research question is
whether the users of health care services anticipate such behavior from their
general practitioner (GP) and, if they do, what consequences such anticipation
has on their preferences regarding financial incentives. Our theoretical model
explains users' preferences for one or another incentives scheme, disentangling
the financial motives (incentives amounts, wealth) from the behavioral ones
(perceived GPs' sensitivity to incentives). We empirically test our theoretical
predictions using data from a survey that elicits individual preferences for
either patient or provider hypothetical incentives in France. The empirical
results confirm the theoretical ones: users tend to prefer incentives to patients
rather than to GPs when the amount of GP incentives is high, when the amount of
patient incentives is low, when they anticipate that their GP's medical decisions
are affected by financial incentives or when their wealth is high. Otherwise,
they prefer their GP to face financial incentives.
PMID- 28497484
TI - CD44 variant isoform 9 emerges in response to injury and contributes to the
regeneration of the gastric epithelium.
AB - The CD44 gene encodes several protein isoforms due to alternative splicing and
post translational modifications. Given that CD44 variant isoform 9 (CD44v9) is
expressed within Spasmolytic Polypeptide/TFF2-Expressing Metaplasia (SPEM) glands
during repair, CD44v9 may be play a funcitonal role during the process of
regeneration of the gastric epithelium. Here we hypothesize that CD44v9 marks a
regenerative cell lineage responsive to infiltrating macrophages during
regeneration of the gastric epithelium. Ulcers were induced in CD44-deficient
(CD44KO) and C57BL/6 (BL6) mice by a localized application of acetic acid to the
serosal surface of the stomach. Gastric organoids expressing CD44v9 were derived
from mouse stomachs and transplanted at the ulcer site of CD44KO mice. Ulcers,
CD44v9 expression, proliferation and histology were measured 1, 3, 5 and 7-days
post-injury. Human-derived gastric organoids were generated from stomach tissue
collected from elderly (>55 years) or young (14-20 years) patients. Organoids
were transplanted into the stomachs of NOD scid gamma (NSG) mice at the site of
injury. Gastric injury was induced in NRG-SGM3 (NRGS) mice harboring human
derived immune cells (hnNRGS) and the immune profile anlayzed by CyTOF. CD44v9
expression emerged within regenerating glands the ulcer margin in response to
injury. While ulcers in BL6 mice healed within 7-days post-injury, CD44KO mice
exhibited loss of repair and epithelial regeneration. Ulcer healing was promoted
in CD44KO mice by transplanted CD55v9-expressing gastric organoids. NSG mice
exhibited loss of CD44v9 expression and gastric repair. Transplantation of human
derived gastric organoids from young, but not aged stomachs promoted repair in
NSG mouse stomachs in response to injury. Finally, compared to NRGS mice, huNRGS
animals exhibited reduced ulcer sizes, an infiltration of human CD162+
macrophages and an emergence of CD44v9 expression in SPEM. Thus, during repair of
the gastic epithelium CD44v9 emerges within a regenerative cell lineage that
coincides with macrophage inflitration within the injured mucosa. Copyright (c)
2017 Pathological Society of Great Britain and Ireland. Published by John Wiley &
Sons, Ltd.
PMID- 28497485
TI - Creating chronicity.
AB - An authentic sickness history is the vantage point for juxtaposing a biomedical
and a biographical-phenomenological reading. What, in a biomedical framework,
appears to be a longstanding state of comorbidity of different and unrelated
types of diseases is rendered transparent in a biographical reading. This
particular reading, evidencing the shortcomings of a biomedical framework
regarding identifying the social sources of an increasingly complex burden of
disease, is reflected upon in light of recent research in the neurosciences.
Thus, the biomedical contribution to a sickness history is demonstrated, with its
resultant multimorbidity, chronification, and complete incapacitation of a woman
despite the continuing and nearly excessive involvement of the health care
system.
PMID- 28497488
TI - The common parasite Toxoplasma gondii induces prostatic inflammation and
microglandular hyperplasia in a mouse model.
AB - BACKGROUND: Inflammation is the most prevalent and widespread histological
finding in the human prostate, and associates with the development and
progression of benign prostatic hyperplasia and prostate cancer. Several factors
have been hypothesized to cause inflammation, yet the role each may play in the
etiology of prostatic inflammation remains unclear. This study examined the
possibility that the common protozoan parasite Toxoplasma gondii induces
prostatic inflammation and reactive hyperplasia in a mouse model. METHODS: Male
mice were infected systemically with T. gondii parasites and prostatic
inflammation was scored based on severity and focality of infiltrating leukocytes
and epithelial hyperplasia. We characterized inflammatory cells with flow
cytometry and the resulting epithelial proliferation with bromodeoxyuridine
(BrdU) incorporation. RESULTS: We found that T. gondii infects the mouse prostate
within the first 14 days of infection and can establish parasite cysts that
persist for at least 60 days. T. gondii infection induces a substantial and
chronic inflammatory reaction in the mouse prostate characterized by monocytic
and lymphocytic inflammatory infiltrate. T. gondii-induced inflammation results
in reactive hyperplasia, involving basal and luminal epithelial proliferation,
and the exhibition of proliferative inflammatory microglandular hyperplasia in
inflamed mouse prostates. CONCLUSIONS: This study identifies the common parasite
T. gondii as a new trigger of prostatic inflammation, which we used to develop a
novel mouse model of prostatic inflammation. This is the first report that T.
gondii chronically encysts and induces chronic inflammation within the prostate
of any species. Furthermore, T. gondii-induced prostatic inflammation persists
and progresses without genetic manipulation in mice, offering a powerful new
mouse model for the study of chronic prostatic inflammation and microglandular
hyperplasia.
PMID- 28497486
TI - 5D whole-heart sparse MRI.
AB - PURPOSE: A 5D whole-heart sparse imaging framework is proposed for simultaneous
assessment of myocardial function and high-resolution cardiac and respiratory
motion-resolved whole-heart anatomy in a single continuous noncontrast MR scan.
METHODS: A non-electrocardiograph (ECG)-triggered 3D golden-angle radial balanced
steady-state free precession sequence was used for data acquisition. The acquired
3D k-space data were sorted into a 5D dataset containing separated cardiac and
respiratory dimensions using a self-extracted respiratory motion signal and a
recorded ECG signal. Images were then reconstructed using XD-GRASP, a
multidimensional compressed sensing technique exploiting correlations/sparsity
along cardiac and respiratory dimensions. 5D whole-heart imaging was compared
with respiratory motion-corrected 3D and 4D whole-heart imaging in nine
volunteers for evaluation of the myocardium, great vessels, and coronary
arteries. It was also compared with breath-held, ECG-gated 2D cardiac cine
imaging for validation of cardiac function quantification. RESULTS: 5D whole
heart images received systematic higher quality scores in the myocardium, great
vessels and coronary arteries. Quantitative coronary sharpness and length were
always better for the 5D images. Good agreement was obtained for quantification
of cardiac function compared with 2D cine imaging. CONCLUSION: 5D whole-heart
sparse imaging represents a robust and promising framework for simplified
comprehensive cardiac MRI without the need for breath-hold and motion correction.
Magn Reson Med 79:826-838, 2018. (c) 2017 International Society for Magnetic
Resonance in Medicine.
PMID- 28497487
TI - Systematic review with meta-analysis: the efficacy of vonoprazan-based triple
therapy on Helicobacter pylori eradication.
AB - BACKGROUND: In order to increase eradication rates, vonoprazan, a novel potassium
competitive acid blocker, has been used in Helicobacter pylori eradication
therapy. AIM: To summarise the results of the efficacy of vonoprazan-based triple
therapy, helping clinicians to better understand the benefit of vonoprazan in the
treatment of H. pylori infection. METHODS: We conducted a systematic literature
search on MEDLINE, EMBASE, and the Cochrane Library using the primary keywords
"vonoprazan," "takecab", "TAK-438," "potassium," "competitive," "potassium
competitive," "Helicobacter," and "pylori." Studies were included if they
evaluated the eradication rate between the vonoprazan-based and proton pump
inhibitor (PPI)-based triple therapies. RESULTS: Ten studies and 10 644 patients
were evaluated. The crude H. pylori eradication rate determined by intention-to
treat analysis was 87.9% and 72.8% in the vonoprazan-based triple therapy and PPI
based triple therapy respectively. The eradication rate of the vonoprazan-based
triple therapy was superior to that of the PPI-based triple therapy (pooled risk
ratio [RR] [95% confidence interval (CI)]=1.19 [1.15-1.24]) In addition, there
was no significant difference in dropout rate due to adverse event between the
regimens (pooled RR of the vonoprazan-based triple therapy [95% CI]=0.69 [0.23
2.03]). The incidence of any adverse events also did not differ between the
regimens (pooled RR [95% CI]=1.02 [0.78-1.34]). CONCLUSIONS: The vonoprazan-based
triple therapy showed superior efficacy in terms of H. pylori eradication as
compared to the PPI-based triple therapy. In addition, the vonoprazan-based
triple therapy showed comparable tolerability and incidence of adverse events.
PMID- 28497489
TI - Efficacy and safety of telaprevir with natural human interferon-beta and
ribavirin in Japanese chronic hepatitis C patients with depression.
AB - AIM: To assess the efficacy and safety of telaprevir (TVR) when used in
combination with natural human interferon-beta (IFN-beta) and ribavirin (RBV) for
genotype 1 patients with depression compared to IFN-beta/RBV therapy in Japan. We
also examined the efficacy of the TVR/IFN-beta/RBV therapy in treatment failure
genotype 2 patients with depression. METHODS: For the genotype 1 patients, 30
patients received TVR (750 mg every 8 h) for 12 weeks combined with IFN-beta and
RBV for 24 weeks (Group A), and 30 received IFN-beta and RBV for 48 weeks (Group
B). For the genotype 2 patients, 14 patients were dosed only with the TVR-based
regimen. RESULTS: The sustained virologic response (SVR) rates for Group A and
Group B were 63.3% and 20.0%, respectively (P = 0.001, likelihood ratio test).
The SVR rate for genotype 2 patients previously treated with pegylated IFN and/or
RBV was 71.4%. No patient dropped out due to exacerbation of depression. The
trend of platelet counts after the drugs were given was similar in the TVR/IFN
beta/RBV therapy group and the IFN-beta/RBV therapy group. Common resistance
associated variants of TVR were identified in 4 of the 13 patients who did not
achieve SVR. CONCLUSION: This study showed that an addition of TVR to IFN
beta/RBV therapy raised SVR in previously treated and untreated genotype 1
patients and previously treated genotype 2 patients with chronic hepatitis C and
depression.
PMID- 28497490
TI - Application of monolithic chromatographic supports in virus research.
AB - Key properties of monolithic chromatographic supports, make them suitable for
separation and/or concentration of large biomolecules, especially virus particles
and viral genomes. One by one, the studies that have been completed so far,
contributed to the knowledge that monolith chromatography has hardly any
limitation to be applied in virus research. Viruses of different sizes,
possessing icosahedral structure and symmetrical morphology, as well as rod
shaped or filamentous viruses with helical structure, even enveloped ones, all of
them could be successfully managed by means of monolith chromatography. Same is
true for viral genomes, primarily when being distinct from other nucleic acid
forms present in a host cell. This review is exclusively focused on viruses. It
describes the application of monolith chromatography to different problematics
within the virus research field. The reviewed achievements offer new
possibilities and trigger new aspects in virology.
PMID- 28497491
TI - Male child with somatic mosaic Osteopathia Striata with Cranial Sclerosis caused
by a novel pathogenic AMER1 frameshift mutation.
AB - Osteopathia striata with cranial sclerosis (OSCS; OMIM #300373) is a rare X
linked dominant condition caused by mutations in the AMER1 gene (also known as
WTX or FAM123B). It is a condition which usually affects females in whom the
clinical phenotype can be extremely variable. Conversely affected males typically
die in utero or during the neonatal period [Perdu et al. (); Clinical Genetics
80: 383-388; Vasiljevic et al. (); Prenatal Diagnosis 35: 302-304]. There have
been a small number of reported cases of surviving males, including three
patients who are somatic mosaic for the condition [Chenier, Noor, Dupuis,
Stavropoulos, & Mendoza-Londono, (); American Journal of Medical Genetics Part A
158A: 2946-2952; Holman et al. (); American Journal of Medical Genetics Part A
155A: 2397-2408; Joseph, Shoji, & Econs, (); The Journal of Clinical
Endocrinology and Metabolism 95: 1506-1507]. We report a case of a male child who
has proven somatic mosaicism for OSCS associated with a novel pathogenic
frameshift mutation, c.607_611delAGGCC (p.Arg203 fs) in AMER1. We describe the
multisystemic clinical features which include macrocephaly with ventriculomegaly
and requirement for ventriculoperitoneal shunt, cleft palate, and respiratory
difficulties after birth requiring tracheostomy insertion, persistent patent
ductus arteriosus, failure to thrive and gastrostomy insertion, growth
retardation, ophthalmoplegia, kidney malformation, cryptorchidism, and
developmental delay. The use of new technologies with next generation sequencing
(NGS) may improve the detection rate of mosaicism in rare conditions.
PMID- 28497492
TI - Dermatitis herpetiformis (Duhring's disease): a therapeutic challenge.
PMID- 28497493
TI - Natural and Synthetic Flavonoids as Potent Mycobacterium tuberculosis UGM
Inhibitors.
AB - This study reports a novel class of inhibitors of uridine 5'-diphosphate (UDP)
galactopyranose mutase (UGM) derived from a screening of natural products. This
enzyme is an essential biocatalyst involved in the cell wall biosynthesis of
Mycobacterium tuberculosis. Flavonoids are potent inhibitors of UGM. The
synthesis of novel methylated flavonoids allowed a structure-activity
relationship analysis to be performed and which functional groups and structural
elements were required for UGM inhibition could be determined. The binding mode
of one of the best inhibitors was found to be noncompetitive. Docking simulations
indicated that this molecule was likely to bind UGM in its open conformation, in
a cavity recently identified as a "druggable" pocket. Importantly, two of the
best inhibitors of the M. tuberculosis UGM displayed moderate activity against
whole M. tuberculosis cells. This study reports the first natural products that
act as inhibitor of UGM. Given the importance of natural products in medicinal
chemistry, these results create new opportunities for the discovery of new
antitubercular agents.
PMID- 28497494
TI - Global assays of fibrinolysis.
AB - Fibrinolysis is an important and integral part of the hemostatic system. Acting
as a balance to blood coagulation, the fibrinolytic system protects the body from
unwanted thrombus formation and occlusion of blood vessels. As long as blood
coagulation and fibrinolysis remain in equilibrium, response to injury, such as
vessel damage, is appropriately regulated. However, alterations in this balance
may lead to thrombosis or bleeding. A variety of methods have been proposed to
assess fibrinolytic activity in blood or its components, but due to the
complexity of the system, the design of a "gold standard" assay that reflects
overall fibrinolysis has remained an elusive goal. In this review, we describe
the most commonly used methods that have been described, such as
thromboelastography (TEG and ROTEM), global fibrinolytic capacity in plasma and
whole blood, plasma turbidity methods, simultaneous thrombin and plasmin
generation assays, euglobulin clot lysis time and fibrin plate methods. All of
these assays have strengths and limitations. We suggest that some methods may be
preferable for detecting hypofibrinolytic conditions, whereas others may be
better for detecting hyperfibrinolytic states.
PMID- 28497495
TI - Tattooing and psoriasis: a case series and review of the literature.
AB - BACKGROUND: Koebner phenomenon (KP) affects from a quarter to a third of the
patients with psoriasis and can occur on tattoos MATERIAL AND METHODS: We
retrospectively reviewed a case series of seven tattooed patients with an
isomorphic response on their tattoos or partial psoriasis patches on their
tattoos. We collected the demographic data, the past history of psoriasis, the
clinical presentation, and the outcomes. We also performed a review of the
literature. We tried to classify the different clinical profile of KP/psoriasis
on tattoos accordingly. RESULTS: Six men and one woman with a median age of 36 +/
6.4 years old were included. Five disclosed a KP in a recent tattoo within days
to 1 month after its completion. Fifteen additional cases were collected from the
literature (8 men, median age 22 +/- 8.2 years old). The delay of psoriasis flare
up after tattooing was rather short, from a few weeks to several months. We found
a high variability in the clinical presentation with five clinical
subtypes/profiles of psoriasis on tattoos. A possible confusion between "genuine"
KP on tattoos and the coincidental occurrence of psoriasis patches on tattoos is
possible in some cases of the literature. Patients were mainly managed locally,
rarely by systemic treatments or biologics. CONCLUSION: Koebner phenomenon on
tattoos may occur in patients with psoriasis under various forms. The evolution
is benign, and psoriasis is not a contraindication for tattooing, but patients
need proper counseling before getting tattooed.
PMID- 28497496
TI - Percutaneous left atrial decompression in adults with refractory cardiogenic
shock supported with veno-arterial extracorporeal membrane oxygenation.
AB - BACKGROUND AND AIM OF THE STUDY: Left ventricular (LV) distention, a recognized
complication in patients supported with veno-arterial extracorporeal membrane
oxygenation (VA-ECMO) for refractory cardiogenic shock, can lead to pulmonary
edema, increased myocardial oxygen consumption, and LV thrombus formation. Atrial
septostomy was examined as a management strategy for LV distension. METHODS: Of
72 patients supported with VA-ECMO, seven patients underwent atrial septostomy
through a trans-septal approach. The primary indication for atrial septostomy was
refractory pulmonary edema. RESULTS: The mean time from ECMO initiation to LA
decompression was 1.3 days (range 0-2 days). There was a 100% procedural success
rate with improvement in pulmonary edema. Five patients survived to discharge
with one patient exhibiting recovery of biventricular function, two patients were
transplanted, one patient was decannulated, and one patient was transitioned to
long-term durable ventricular assist device. Two patients died, one from multi
organ failure and one with severe anoxic brain injury. CONCLUSION: Atrial
septostomy is an effective method of LV decompression that can be performed
safely with a high success rate.
PMID- 28497497
TI - Simultaneous measurement of macro- and microvascular blood flow and oxygen
saturation for quantification of muscle oxygen consumption.
AB - PURPOSE: To investigate the relationship between blood flow and oxygen
consumption in skeletal muscle, a technique called "Velocity and Perfusion,
Intravascular Venous Oxygen saturation and T2*" (vPIVOT) is presented. vPIVOT
allows the quantification of feeding artery blood flow velocity, perfusion,
draining vein oxygen saturation, and muscle T2*, all at 4-s temporal resolution.
Together, the measurement of blood flow and oxygen extraction can yield muscle
oxygen consumption ( VO2) via the Fick principle. METHODS: In five subjects,
vPIVOT-derived results were compared with those obtained from stand-alone
sequences during separate ischemia-reperfusion paradigms to investigate the
presence of measurement bias. Subsequently, in 10 subjects, vPIVOT was applied to
assess muscle hemodynamics and VO2 following a bout of dynamic plantar flexion
contractions. RESULTS: From the ischemia-reperfusion paradigm, no significant
differences were observed between data from vPIVOT and comparison sequences.
After exercise, the macrovascular flow response reached a maximum 8 +/- 3 s after
relaxation; however, perfusion in the gastrocnemius muscle continued to rise for
101 +/- 53 s. Peak VO2 calculated based on mass-normalized arterial blood flow or
perfusion was 15.2 +/- 6.7 mL O2 /min/100 g or 6.0 +/- 1.9 mL O2 /min/100 g,
respectively. CONCLUSIONS: vPIVOT is a new method to measure blood flow and
oxygen saturation, and therefore to quantify muscle oxygen consumption. Magn
Reson Med 79:846-855, 2018. (c) 2017 International Society for Magnetic Resonance
in Medicine.
PMID- 28497498
TI - Cryoprotection and banking of living cells in a 3D multiple emulsion-based
carrier.
AB - The ability to preserve stem cells/cells with minimal damage for short and long
periods of time is essential for advancements in biomedical therapies and
biotechnology. New methods of cell banking are continuously needed to provide
effective damage prevention to cells. This paper puts forward a solution to the
problem of the low viability of cells during cryopreservation in a traditional
suspension and storage by developing innovative multiple emulsion-based carriers
for the encapsulation and cryopreservation of cells. During freezing-thawing
processes, irreversible damage to cells occurs as a result of the formation of
ice crystals, cell dehydration, and the toxicity of cryoprotectant. The proposed
method was effective due to the "flexible" protective structure of multiple
emulsions, which was proven by a high cell survival rate, above 90%. Results make
new contributions in the fields of cell engineering and biotechnology and
contribute to the development of methods for banking biological material.
PMID- 28497500
TI - Adverse effects of leptin on histone-to-protamine transition during
spermatogenesis are prevented by melatonin in Sprague-Dawley rats.
AB - This study examines the effect of melatonin on leptin-induced changes in
transition of histone to protamine in adult rats during spermatogenesis. Twelve
week-old Sprague-Dawley rats were randomised into control, leptin-, leptin
melatonin-10-, leptin-melatonin-20- and melatonin-10-treated groups with six rats
per group. Leptin was given via intraperitoneal injections (i.p.) daily for 42
days (60 MUg/kg body weight). Rats in the leptin- and melatonin-treated groups
were given either 10 or 20 mg day-1 kg-1 body weight of leptin in drinking
water. Melatonin-10-treated group received only 10 mg of melatonin day-1 kg-1
body weight in drinking water for 42 days. Control rats received 0.1 ml of 0.9%
saline. Upon completion of the treatment, sperm count, morphology and histone-to
protamine ratio were estimated. Gene expression of HAT, HDAC1, HDAC2, H2B, H2A,
H1, PRM1, PRM2, TNP1 and TNP2 was determined. Data were analysed using ANOVA.
Sperm count was significantly lower, whereas the fraction of spermatozoa with
abnormal morphology, the ratio of histone-to-protamine transition and the
expressions of HAT, HDAC1, HDAC2, H2B, H2A, H1, PRM1 were significantly higher in
leptin-treated rats than those in controls or melatonin-treated rats. It appears
that exogenous leptin administration adversely affects histone-to-protamine
transition, which is prevented by concurrent administration of melatonin.
PMID- 28497499
TI - Applying characteristic fragment filtering for rapid detection and identification
of ingredients in rhubarb by HPLC coupled with linear ion trap-Orbitrap mass
spectrometry.
AB - Chemical characteristic fragment filtering in MSn chromatograms was proposed to
detect and identify the components in rhubarb rapidly using high-performance
liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry.
Characteristic fragments consist of diagnostic ions and neutral loss fragments.
Characteristic fragment filtering is a postacquisition data mining method for the
targeted screening of groups with specific structures, including three steps:
first, in order to comprehensively summarize characteristic fragments for global
identification of the ingredients in rhubarb, representative authentic standards
of dominant chemical categories contained in rhubarb were chosen, from which
fragmentation rules and a characteristic fragments schedule were proposed;
second, characteristic fragment filtering was used to rapidly recognize analogous
skeletons; finally, combined with retention time, accurate mass, characteristic
fragments, and previous literature, the structures of the filtered compounds were
identified or tentatively characterized. As a result, a total of 271 compounds
were detected and identified in rhubarb, including 34 anthraquinones, 83
anthrones, 46 tannins, 17 stilbenes, 24 phenylbutanones, 26 acylglucosides, 26
chromones, and 15 other compounds, 69 of which are potentially new compounds. The
proposed characteristic fragment filtering strategy would be a reference for the
large-scale detection and identification of the ingredients of herbal medicines.
PMID- 28497501
TI - Assessing the role of Hartree-Fock exchange, correlation energy and long range
corrections in evaluating ionization potential, and electron affinity in density
functional theory.
AB - Accurate determination of ionization potentials (IPs), electron affinities (EAs),
fundamental gaps (FGs), and HOMO, LUMO energy levels of organic molecules play an
important role in modeling and predicting the efficiencies of organic
photovoltaics, OLEDs etc. In this work, we investigate the effects of Hartree
Fock (HF) Exchange, correlation energy, and long range corrections in predicting
IP and EA in Hybrid Functionals. We observe increase in percentage of HF exchange
results in increase of IPs and decrease in EAs. Contrary to the general
expectations inclusion of both HF exchange and correlation energy (from the
second order perturbation theory MP2) leads to poor prediction. Range separated
Hybrid Functionals are found to be more reliable among various DFT Functionals
investigated. DFT Functionals predict accurate IPs whereas post HF methods
predict accurate EAs. (c) 2017 Wiley Periodicals, Inc.
PMID- 28497502
TI - Improving outcome of fungal diseases - Guiding experts and patients towards
excellence.
AB - Invasive fungal infections are on the rise and during recent years understanding
the epidemiology of fungal infections improved. Over 1 billion people are
affected and 25 million patients are at imminent risk of severe organ damage or
death due to fungal infection. The European Confederation of Medical Mycology
(ECMM), founded in 1993, is the roof organisation of 23 National Medical Mycology
Societies in Europe. ECMM fights fungal infections at various levels, by creating
and distributing scientific knowledge and promoting scientific exchange. In
response to the increasing prevalence and management complexity of invasive
fungal infections, ECMM recently launched three additional initiatives
(https://www.ecmm.info/). (i) ECMM together with other European infectious
diseases societies created a comprehensive set of European guidelines for the
diagnostic and therapeutic management of invasive fungal infections. (ii) ECMM
founded the ECMM Academy awarding fellow status (FECMM) to outstanding
researchers who advanced medical mycology. The academy aims at strengthening
networking activities between these researchers. (iii) Centres throughout the
world can apply for ECMM Excellence Center Status. Following such application on
site auditing of up to three levels of mycological work (clinical,
microbiological, epidemiological/clinical trials) evaluates the excellence of a
centre along predefined criteria. All three initiatives share a common ambition;
they aim at improving outcome of fungal diseases through guiding experts and
patients towards excellence. Acknowledging fungal infections as a global problem,
all three initiatives explicitly reach out beyond European borders.
PMID- 28497503
TI - Establishing Australian school re-entry service guidelines for children diagnosed
with cancer.
PMID- 28497504
TI - Semiconducting Coordination Polymers Based on the Predesigned Ternary Te-Fe-Cu
Carbonyl Cluster and Conjugation-Interrupted Dipyridyl Linkers.
AB - A series of semiconducting cluster-incorporated Cu-based coordination polymers,
namely, 1D zigzag polymers [{TeFe3 (CO)9 Cu2 }(L)]n (L=1,2-bis(4-pyridyl)ethane
(bpea), 1; L=1,2-bis(4-pyridyl)ethylene (bpee), 5), 2D honeycomb-like polymers
[{TeFe3 (CO)9 Cu}Cu(L)2.5 ]n (L=bpea, 2; L=bpee, 6), and 2D wave-like cation
anion polymer [{Cu2 (L)4 }({TeFe3 (CO)9 Cu}2 (L))]n (L=1,3-bis(4-pyridyl)propane
(bpp), 4), as well as the macrocycle [{TeFe3 (CO)9 Cu2 }2 (bpp)2 ] (3) have been
quantitatively synthesized via the liquid-assisted grinding from the pre-designed
cluster [TeFe3 (CO)9 Cu2 (MeCN)2 ] with conjugated or conjugation-interrupted
dipyridyl linkers. Notably, the most conjugation-interrupted bpp-bridged polymer
4 exhibited extraordinary semiconducting characteristics with an ultra-narrow
bandgap of 1.43 eV and a DC conductivity of 1.5*10-2 Omega-1 cm-1 , which
violates our knowledge, mainly attributed to the through-space electron transport
via non-classical C-H???O(carbonyl) hydrogen bonds and aromatic C-H???pi
interactions. The incorporated Te-Fe-CO anions can not only provide numerous
possibilities for secondary interactions within these Cu-based polymers but also
serve as a redox-active coordination ligand to promote their conductivities. The
intriguing structure-property relationships were studied by X-ray and DFT
analyses and further demonstrated by significant change in the oxidation state of
Cu atoms by XPS and Cu K-edge XANES.
PMID- 28497505
TI - Resurgence of rabies in Hungary during 2013-2014: An attempt to track the origin
of identified strains.
AB - In 2013-2014, accumulation of rabies episodes raised concerns regarding ongoing
elimination programme in Hungary. Nearly four dozen cases were identified over a
13-month period in the central region of the country far behind the immunization
zones. Although the outbreak was successfully controlled, the origin of disease
remained unknown. In this study, we sequenced the partial N and G genes from 47
Hungarian rabies virus (RV) strains isolated from the 2013-2014 outbreak.
Sequencing and phylogenetic analysis of the N and G genes showed that the
Hungarian RV isolates share high nucleotide similarity among each other (up to
100%). When analysing the N gene, comparable sequence similarity was seen between
the outbreak strains and some historic Romanian RV strains. Unfortunately, in the
lack of available sequence data from the Romanian RV strains, the genetic
relationship within the G gene could not be determined. Phylogenetic analysis of
Hungarian RV isolates detected in the past revealed that multiple independent RV
lineages circulated in our country over the past 25 years. The parental strain of
the 2013-2014 outbreak may have been imported independently perhaps from east
through transborder movement of a reservoir animal. Next to the introduction,
this imported RV strain seems to have spread clonally in the affected area. Our
findings indicate that despite effective control measures that, overall,
minimized the incidence of rabies over the past decade, field and laboratory
monitoring needs to be continued to make rabies elimination programme in Hungary
successful.
PMID- 28497506
TI - Left ventricular obstruction caused by a large hiatal hernia.
AB - A 76-year-old man was admitted to our emergency department owing to chest pain,
which started immediately after lunch. Although electrocardiogram revealed ST
segment elevation with hyperacute T-wave changes in the anterior lead tracings,
emergency coronary angiography revealed normal coronary arteries.
Echocardiography revealed left ventricular (LV) compression with left ventricular
obstruction (LVO) caused by an echogenic mass. Computed tomography clearly
revealed compression of both left atrial (LA) and LV by a large hiatal hernia. A
large hiatal hernia can induce cardiac symptoms resulting from cardiac
compression. This case highlights a possible association between chest pain and
LVO caused by a hiatal hernia.
PMID- 28497507
TI - Ferrocene- and Biferrocene-Containing Macrocycles towards Single-Molecule
Electronics.
AB - Cyclic multiredox centered systems are currently of great interest, with new
compounds being reported and developments made in understanding their behavior.
Efficient, elegant, and high-yielding (for macrocyclic species) synthetic routes
to two novel alkynyl-conjugated multiple ferrocene- and biferrocene-containing
cyclic compounds are presented. The electronic interactions between the
individual ferrocene units have been investigated through electrochemistry,
spectroelectrochemistry, density functional theory (DFT), and crystallography to
understand the effect of cyclization on the electronic properties and structure.
PMID- 28497508
TI - New horizons for mental health research in intellectual disabilities.
PMID- 28497509
TI - Characteristics and prognosis of glomangiopericytomas: A systematic review.
AB - BACKGROUND: Glomangiopericytoma belongs to the category of borderline/low
malignant-potential tumors of the sinonasal tract, but no studies about prognosis
have been reported. METHODS: To define the characteristics of glomangiopericytoma
and to identify its prognostic factors, a systematic review was performed. A
total of 337 cases of glomangiopericytomas were analyzed. RESULTS: Patients with
glomangiopericytoma demonstrating resection margin involvement and receiving
radiotherapy/chemotherapy had a significantly worse disease-free survival time (P
= .014 and .006, respectively). Patients with glomangiopericytoma had a tendency
toward longer overall survival when they were diagnosed at a younger age (<=60
years; P = .001), did not demonstrate marginal involvement (P = .032),
recurrence/metastasis (P = .002), or radiotherapy/chemotherapy (P = .010), and
had a right-sided tumor (P < .001), actin-immunopositivity (P < .001), and CD34
/BCL2-immunonegativities (P = .002 and .019, respectively). By multivariate
analysis, actin (P < .001) and CD34 (P = .002) immunostaining were significantly
related to the overall survival of patients with glomangiopericytoma. CONCLUSION:
Actin and CD34 immunostaining could be used as independent prognostic indicators
of glomangiopericytomas.
PMID- 28497510
TI - The effect of health care expenditure on patient outcomes: Evidence from English
neonatal care.
AB - The relationship between health care expenditure and health outcomes has been the
subject of recent academic inquiry in order to inform cost-effectiveness
thresholds for health technology assessment agencies. Previous studies in public
health systems have relied upon data aggregated at the national or regional
level; however, there remains debate about whether the supply side effect of
changes to expenditure are identifiable using data at this level of aggregation.
We use detailed patient data derived from electronic neonatal records across
England along with routinely available cost data to estimate the effect of
changes to patient expenditure on clinical health outcomes in a well-defined
patient population. A panel of 32 neonatal intensive care units for the period
2009-2013 was constructed. Accounting for the potential endogeneity of
expenditure a L100 increase in the cost per intensive care cot day (sample
average cost: L1,127) is estimated to reduce the risk of mortality of 0.38
percentage points (sample average mortality: 11.0%) in neonatal intensive care.
This translates into a cost per life saved in neonatal intensive care of
approximately L420,000.
PMID- 28497511
TI - Effects of medical trainees' weight-loss history on perceptions of patients with
obesity.
AB - CONTEXT: Medical professionals often express weight-biased attitudes. Prior
research suggests that people who overcome a challenge are critical of
individuals who struggle to overcome the same challenge. Thus, medical trainees
who have successfully achieved and maintained weight loss may express greater
weight bias and more critical attitudes toward patients with obesity who fail to
overcome these challenges. OBJECTIVES: This study was designed to determine the
effects of medical trainees' weight-loss history on weight-biased attitudes and
responses to patients with varying weight-loss outcomes. METHODS: An online
survey was completed by 219 medical students and internal medicine residents.
Participants' weight-biased attitudes were assessed before they were randomly
assigned to read one of three patient vignettes in which the patient lost no
weight, lost/regained weight, or lost/maintained weight. Independent measures
included trainee gender, trainee weight loss and maintenance, and the three
experimental conditions of patient outcomes. Dependent measures included the Anti
Fat Attitudes (AFA) Questionnaire's Willpower and Dislike subscales, ratings (on
a scale of 1-7) of compassion, frustration, and blame toward the patients
presented in the vignettes, and perceptions of the physician-patient alliance.
All analyses controlled for trainee body mass index. RESULTS: Among trainees,
67.1% reported having successfully lost weight. Of those who had lost weight,
79.5% reported maintaining their weight loss. Trainees who had successfully
lost/maintained weight expressed less compassion toward patients across vignettes
(5.4 +/- 1.2 versus 5.9 +/- 1.2; p<0.05), and more blame toward the patient who
lost/regained weight than did trainees who had lost/regained weight (3.4 +/- 1.3
versus 2.3 +/- 1.3; p<0.01). Overall, the patient who did not lose weight was
viewed most negatively, followed by the patient who lost/regained (all p-values <
0.05). Female (but not male) trainees who had successfully lost weight expressed
stronger weight-biased attitudes on the AFA scales than did those who had never
lost weight (all p-values < 0.01). CONCLUSIONS: Medical trainees' personal
success with weight loss and maintenance may negatively affect their perceptions
of patients with obesity who struggle with weight management.
PMID- 28497512
TI - Children's intuitive sense of number develops independently of their perception
of area, density, length, and time.
AB - Young children can quickly and intuitively represent the number of objects in a
visual scene through the Approximate Number System (ANS). The precision of the
ANS - indexed as the most difficult ratio of two numbers that children can
reliably discriminate - is well known to improve with development: whereas
infants require relatively large ratios to discriminate number, children can
discriminate finer and finer changes in number between toddlerhood and early
adulthood. Which factors drive the developmental improvements in ANS precision?
Here, we investigate the influence of four non-numeric dimensions - area,
density, line length, and time - on ANS development, exploring the degree to
which the ANS develops independently from these other dimensions, from inhibitory
control, and from domain-general factors such as attention and working memory
that are shared between these tasks. A sample of 185 children between the ages of
2 and 12 years completed five discrimination tasks: approximate number, area,
density, length, and time. We report three main findings. First, logistic growth
models applied to both accuracy and Weber fractions (w; an index of ANS
precision) across age reveal distinct developmental trajectories across the five
dimensions: while area and length develop by adolescence, time and density do not
develop fully until early adulthood, with ANS precision developing at an
intermediate rate. Second, we find that ANS precision develops independently of
the other four dimensions, which in turn develop independently of the ANS. Third,
we find that ANS precision also develops independently from individual
differences in inhibitory control (indexed as the difference in accuracy and w
between Congruent and Incongruent ANS trials). Together, these results are the
first to provide evidence for domain-specific improvements in ANS precision, and
place children's maturing perception of number, space, and time into a broader
developmental context.
PMID- 28497513
TI - Supporting new (and not so new) health professionals.
PMID- 28497514
TI - Running a successful trainee conference.
PMID- 28497515
TI - Reflecting on simulation.
PMID- 28497516
TI - Learning with and from peers.
PMID- 28497517
TI - Reflecting on medical student surgical conferences.
PMID- 28497518
TI - An innovative programme for premedical students.
PMID- 28497519
TI - Living with advanced cancer and the role of the primary care provider: The
missing piece in the survivorship discourse.
AB - The period of survivorship has been identified as a distinct phase of the cancer
continuum, and the key role of primary care providers in caring for cancer
survivors has been recognized. However, much of the focus to date has been placed
on cancer survivors who are treated with curative intent and survive cancer-free.
Receiving less attention are those who are living with advanced, non-curative
cancer. In this commentary, we review the current evidence about the
characteristics of these survivors, their unmet needs and receipt of health care.
We offer insights into future research, education and policy initiatives aiming
to enhance the care for this population.
PMID- 28497520
TI - Nitrous oxide for procedural analgesia at home in a child with epidermolysis
bullosa.
AB - Epidermolysis bullosa comprises a range of conditions characterized by fragile
skin with painful blistering induced by minor trauma and friction. The Dowling
Meara variant is a severe form characterized by disseminated painful blistering
requiring lifelong skin and wound care. The natural history of the disease is
characterized by a chronic course that tends to improve with advancing age.
Various multimodal analgesic strategies have been proposed for painful procedures
in children with epidermolysis bullosa. In this case report, we describe the use
of nitrous oxide for pain control at home of blister treatments in a 4-year-old
child with the Dowling-Meara variant.
PMID- 28497521
TI - Erratum: "A new method to retrieve phase information for equiangular fan beam
differential phase contrast computed tomography" [Med. Phys. 40, 031911(8pp.)
(2013)].
PMID- 28497522
TI - Erratum: "Experimental demonstration of passive acoustic imaging in the human
skull cavity using CT-based aberration corrections" [Med. Phys. 42, 4385-4400
(2015)].
PMID- 28497523
TI - High MELD score does not adversely affect outcome of living donor liver
transplantation: Experience in 1000 recipients.
AB - In countries where deceased organ donation is scarce, there is a big gap between
demand and supply of organs and living donor liver transplantation (LDLT) plays
an important role in meeting this unmet need. This study was conducted to analyze
the effect of pretransplant Model for End-stage Liver Disease (MELD) score on
outcomes following LDLT. The outcome of 1000 patients who underwent LDLT from
July 2010 to March 2015 was analyzed retrospectively. Patients were grouped into
low MELD<25 and high MELD >=25 score to compare short-term outcomes. Cumulative
overall survival rates were calculated using Kaplan-Meier methods. A total of 849
recipients were in low MELD group (Mean MELD=16.90+/-9.2) and 151 were in high
MELD group (Mean MELD=28.77+/-7.2). No significant difference in etiology of CLD
was observed between groups except for a higher prevalence of hepatitis C virus
(29.6% vs 19.9%, P=.01) in low MELD patients. No significant difference was
observed in 1-year survival (88.5% vs 84.1%, P=.12) between the groups. The
multivariate analysis showed that pretransplant MELD score does not predict
survival of recipients. Pretransplant high MELD score does not adversely affect
outcomes after LDLT. In view of shortage of deceased organs, LDLT can be a good
option in high MELD recipients.
PMID- 28497524
TI - Changing minds: Children's inferences about third party belief revision.
AB - By the age of 5, children explicitly represent that agents can have both true and
false beliefs based on epistemic access to information (e.g., Wellman, Cross, &
Watson, 2001). Children also begin to understand that agents can view identical
evidence and draw different inferences from it (e.g., Carpendale & Chandler,
1996). However, much less is known about when, and under what conditions,
children expect other agents to change their minds. Here, inspired by formal
ideal observer models of learning, we investigate children's expectations of the
dynamics that underlie third parties' belief revision. We introduce an agent who
has prior beliefs about the location of a population of toys and then observes
evidence that, from an ideal observer perspective, either does, or does not
justify revising those beliefs. We show that children's inferences on behalf of
third parties are consistent with the ideal observer perspective, but not with a
number of alternative possibilities, including that children expect other agents
to be influenced only by their prior beliefs, only by the sampling process, or
only by the observed data. Rather, children integrate all three factors in
determining how and when agents will update their beliefs from evidence.
PMID- 28497526
TI - Prevention, removal and inactivation of Escherichia coli and Staphylococcus
aureus biofilms using selected monoterpenes of essential oils.
AB - AIMS: The aim of this study was to investigate the antibiofilm potential of five
essential oils (EOs) components with cyclic (sabinene-SAB, carveol-C1, carvone
C2) and acyclic (citronellol-C3 and citronellal-C4) structures against
Escherichia coli and Staphylococcus aureus. METHODS AND RESULTS: The selected EOs
components prevented biofilm set-up, with C3 and C4 causing remarkable effects.
When applied against pre-established biofilms, they promoted high biomass removal
and inactivation of biofilm cells. Moreover, no viable E. coli biofilm cells were
detected after exposure to SAB at 5*MIC and 10*MIC and significant viability
decrease was observed for both bacteria with the other EOs components. SAB, C3
and C4 caused the most prominent effects apparently due to their octanol-water
partition coefficient (Po/w), the number of rotatable bonds (n-ROTB) and the free
hydroxyl groups. CONCLUSIONS: The overall results demonstrated that the selected
EOs components, particularly SAB, C3 and C4 are of interest as new lead molecules
to both prevent biofilm set-up and to control pre-established biofilms of E. coli
and S. aureus. This article is protected by copyright. All rights reserved.
PMID- 28497527
TI - Uncommon cause of pulmonary hypertension.
PMID- 28497525
TI - Risk of End-Stage Renal Disease in HIV-Positive Potential Live Kidney Donors.
AB - New federal regulations allow HIV-positive individuals to be live kidney donors;
however, potential candidacy for donation is poorly understood given the
increased risk of end-stage renal disease (ESRD) associated with HIV infection.
To better understand this risk, we compared the incidence of ESRD among 41 968
HIV-positive participants of North America AIDS Cohort Collaboration on Research
and Design followed for a median of 5 years with the incidence of ESRD among
comparable HIV-negative participants of National Health and Nutrition Examination
III followed for a median of 14 years. We used risk associations from
multivariable Cox proportional hazards regression to derive cumulative incidence
estimates for selected HIV-positive scenarios (no history of diabetes,
hypertension, AIDS, or hepatitis C virus coinfection) and compared these
estimates with those from similarly selected HIV-negative scenarios. For 40-year
old HIV-positive individuals with health characteristics that were similar to
those of age-matched kidney donors, viral load <400 copies/mL, and CD4+ count
>=500 cells/MUL, the 9-year cumulative incidence of ESRD was higher than that of
their HIV-negative peers, yet still low: 2.5 versus 1.1 per 10 000 among white
women, 3.0 versus 1.3 per 10 000 among white men, 13.2 versus 3.6 per 10 000
among black women, and 15.8 versus 4.4 per 10 000 among black men. HIV-positive
individuals with no comorbidities and well-controlled disease may be considered
low-risk kidney donor candidates.
PMID- 28497528
TI - Frequency-Swept Integrated Solid Effect.
AB - The efficiency of continuous wave dynamic nuclear polarization (DNP) experiments
decreases at the high magnetic fields used in contemporary high-resolution NMR
applications. To recover the expected signal enhancements from DNP, we explored
time domain experiments such as NOVEL which matches the electron Rabi frequency
to the nuclear Larmor frequency to mediate polarization transfer. However,
satisfying this matching condition at high frequencies is technically demanding.
As an alternative we report here frequency-swept integrated solid effect (FS-ISE)
experiments that allow low power sweeps of the exciting microwave frequencies to
constructively integrate the negative and positive polarizations of the solid
effect, thereby producing a polarization efficiency comparable to (+/-10 %
difference) NOVEL. Finally, the microwave frequency modulation results in field
profiles that exhibit new features that we coin the "stretched" solid effect.
PMID- 28497529
TI - AAPM medical physics practice guideline 6.a.: Performance characteristics of
radiation dose index monitoring systems.
AB - The American Association of Physicists in Medicine (AAPM) is a nonprofit
professional society whose primary purposes are to advance the science, education
and professional practice of medical physics. The AAPM has more than 8,000
members and is the principal organization of medical physicists in the United
States. The AAPM will periodically define new practice guidelines for medical
physics practice to help advance the science of medical physics and to improve
the quality of service to patients throughout the United States. Existing medical
physics practice guidelines will be reviewed for the purpose of revision or
renewal, as appropriate, on their fifth anniversary or sooner. Each medical
physics practice guideline represents a policy statement by the AAPM, has
undergone a thorough consensus process in which it has been subjected to
extensive review, and requires the approval of the Professional Council. The
medical physics practice guidelines recognize that the safe and effective use of
diagnostic and therapeutic radiology requires specific training, skills, and
techniques, as described in each document. Reproduction or modification of the
published practice guidelines and technical standards by those entities not
providing these services is not authorized. The following terms are used in the
AAPM practice guidelines: *Must and Must Not: Used to indicate that adherence to
the recommendation is considered necessary to conform to this practice guideline.
*Should and Should Not: Used to indicate a prudent practice to which exceptions
may occasionally be made in appropriate circumstances.
PMID- 28497530
TI - Short-term Memory in Childhood Dyslexia: Deficient Serial Order in Multiple
Modalities.
AB - In children with dyslexia, deficits in working memory have not been well
specified. We assessed second-grade children with dyslexia, with and without
concomitant specific language impairment, and children with typical development.
Immediate serial recall of lists of phonological (non-word), lexical (digit),
spatial (location) and visual (shape) items were included. For the latter three
modalities, we used not only standard span but also running span tasks, in which
the list length was unpredictable to limit mnemonic strategies. Non-word
repetition tests indicated a phonological memory deficit in children with
dyslexia alone compared with those with typical development, but this difference
vanished when these groups were matched for non-verbal intelligence and language.
Theoretically important deficits in serial order memory in dyslexic children,
however, persisted relative to matched typically developing children. The
deficits were in recall of (1) spoken digits in both standard and running span
tasks and (2) spatial locations, in running span only. Children with dyslexia
with versus without language impairment, when matched on non-verbal intelligence,
had comparable serial order memory, but differed in phonology. Because serial
orderings of verbal and spatial elements occur in reading, the careful
examination of order memory may allow a deeper understanding of dyslexia and its
relation to language impairment. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28497531
TI - Exposure enriched outcome dependent designs for longitudinal studies of gene
environment interaction.
AB - Joint effects of genetic and environmental factors have been increasingly
recognized in the development of many complex human diseases. Despite the
popularity of case-control and case-only designs, longitudinal cohort studies
that can capture time-varying outcome and exposure information have long been
recommended for gene-environment (G * E) interactions. To date, literature on
sampling designs for longitudinal studies of G * E interaction is quite limited.
We therefore consider designs that can prioritize a subsample of the existing
cohort for retrospective genotyping on the basis of currently available outcome,
exposure, and covariate data. In this work, we propose stratified sampling based
on summaries of individual exposures and outcome trajectories and develop a full
conditional likelihood approach for estimation that adjusts for the biased
sample. We compare the performance of our proposed design and analysis with
combinations of different sampling designs and estimation approaches via
simulation. We observe that the full conditional likelihood provides improved
estimates for the G * E interaction and joint exposure effects over uncorrected
complete-case analysis, and the exposure enriched outcome trajectory dependent
design outperforms other designs in terms of estimation efficiency and power for
detection of the G * E interaction. We also illustrate our design and analysis
using data from the Normative Aging Study, an ongoing longitudinal cohort study
initiated by the Veterans Administration in 1963. Copyright (c) 2017 John Wiley &
Sons, Ltd.
PMID- 28497532
TI - Arabidopsis thaliana EPOXIDE HYDROLASE1 (AtEH1) is a cytosolic epoxide hydrolase
involved in the synthesis of poly-hydroxylated cutin monomers.
AB - Epoxide hydrolases (EHs) are present in all living organisms. They have been
extensively characterized in mammals; however, their biological functions in
plants have not been demonstrated. Based on in silico analysis, we identified
AtEH1 (At3g05600), a putative Arabidopsis thaliana epoxide hydrolase possibly
involved in cutin monomer synthesis. We expressed AtEH1 in yeast and studied its
localization in vivo. We also analyzed the composition of cutin from A. thaliana
lines in which this gene was knocked out. Incubation of recombinant AtEH1 with
epoxy fatty acids confirmed its capacity to hydrolyze epoxides of C18 fatty acids
into vicinal diols. Transfection of Nicotiana benthamiana leaves with constructs
expressing AtEH1 fused to enhanced green fluorescent protein (EGFP) indicated
that AtEH1 is localized in the cytosol. Analysis of cutin monomers in loss-of
function Ateh1-1 and Ateh1-2 mutants showed an accumulation of 18-hydroxy-9,10
epoxyoctadecenoic acid and a concomitant decrease in corresponding vicinal diols
in leaf and seed cutin. Compared with wild-type seeds, Ateh1 seeds showed delayed
germination under osmotic stress conditions and increased seed coat permeability
to tetrazolium red. This work reports a physiological role for a plant EH and
identifies AtEH1 as a new member of the complex machinery involved in cutin
synthesis.
PMID- 28497533
TI - The Saudi National Mental Health Survey: Methodological and logistical challenges
from the pilot study.
AB - Several challenges exist in carrying out nation-wide epidemiological surveys in
the Kingdom of Saudi Arabia (KSA) due to the unique characteristics of its
population. The objectives of this report are to review these challenges and the
lessons learnt about best practices in meeting these challenges from the
extensive piloting of the Saudi National Mental Health Survey (SNMHS), which is
being carried out as part of the World Mental Health (WMH) Survey Initiative. We
focus on challenges involving sample design, instrumentation, and data collection
procedures. The SNMHS will ultimately provide crucial data for health policy
makers and mental health specialists in KSA.
PMID- 28497535
TI - Stimuli-Responsive Polymeric Nanoparticles.
AB - There is increasing evidence that stimuli-responsive nanomaterials have become
significantly critical components of modern materials design and technological
developments. Recent advances in synthesis and fabrication of stimuli-responsive
polymeric nanoparticles with built-in stimuli-responsive components (Part A) and
surface modifications of functional nanoparticles that facilitate responsiveness
(Part B) are outlined here. The synthesis and construction of stimuli-responsive
spherical, core-shell, concentric, hollow, Janus, gibbous/inverse gibbous, and
cocklebur morphologies are discussed in Part A, with the focus on shape, color,
or size changes resulting from external stimuli. Although inorganic/metallic
nanoparticles exhibit many useful properties, including thermal or electrical
conductivity, catalytic activity, or magnetic properties, their assemblies and
formation of higher order constructs are often enhanced by surface modifications.
Section B focuses on selected surface reactions that lead to responsiveness
achieved by decorating nanoparticles with stimuli-responsive polymers. Although
grafting-to and grafting-from dominate these synthetic efforts, there are
opportunities for developing novel synthetic approaches facilitating controllable
recognition, signaling, or sequential responses. Many nanotechnologies utilize a
combination of organic and inorganic phases to produce ceramic or metallic
nanoparticles. One can envision the development of new properties by combining
inorganic (metals, metal oxides) and organic (polymer) phases into one
nanoparticle designated as "ceramers" (inorganics) and "metamers" (metallic).
PMID- 28497534
TI - Effects of testosterone replacement therapy on metabolic syndrome among Japanese
hypogonadal men: A subanalysis of a prospective randomised controlled trial
(EARTH study).
AB - We investigated the effects of testosterone replacement therapy (TRT) on
metabolic factors among hypogonadal men with a metabolic syndrome. From the study
population of the EARTH study, which was a randomised controlled study in Japan,
65 hypogonadal patients with a metabolic syndrome, comprising the TRT group (n =
32) and controls (n = 33), were included in this study analysis. The TRT group
was administered 250 mg of testosterone enanthate as an intramuscular injection
every 4 weeks for 12 months. Waist circumference, body mass index, body fat
volume and blood pressure were measured in all patients at baseline and at 12
months. In addition, blood biochemical data, including total cholesterol,
triglyceride (TG), HDL cholesterol, fasting plasma glucose (FPG) and haemoglobin
A1c (HbA1c) levels, were also evaluated. Changes in these categories from
baseline to 12 months were compared between the TRT and control groups, with
significant differences observed in waist circumference, body fat percentage,
FPG, TG and HbA1c levels. No significant differences were observed in other
parameters. TRT for 1 year was associated with improvements in some metabolic
factors among Japanese men with hypogonadism and metabolic syndrome.
PMID- 28497536
TI - Robotic guided waterjet cutting technique for high tibial dome osteotomy: A pilot
study.
AB - BACKGROUND: Oscillating saws generate high levels of heat (up to 150 degrees C),
which can lead to tissue necrosis, delayed healing and infection. Abrasive
waterjet-cutting techniques have been described as a new tool to perform bone
cuts, with less heat generation. METHODS: Four lower-limbs of four human alcohol
conserved cadavers were tested. Navigation references were attached to the tibia
and an intraoperative fluoroscopy-based 3D scan was obtained. A 1.2 mm diameter
nozzle was attached to a robotic arm, which was guided to follow a pre-specified
path. In addition, a self-designed jet-absorber was applied to protect the
posterior neurovascular structures. Magnesium was added as an abrasive substance
to improve the cutting ability of the waterjet. RESULTS: In all four cadavers,
the osteotomies could be carried out as planned, resulting in smooth cut
surfaces. No damage to the soft-tissues was observed. CONCLUSIONS: The advantages
of abrasive waterjet-cutting give it great potential in orthopaedic surgery. A
current disadvantage is the amount of magnesium solute that is left on the
surgical field and can be harmful to the patient.
PMID- 28497537
TI - ICSH recommendations for modified and alternate methods measuring the erythrocyte
sedimentation rate.
AB - INTRODUCTION: The gold standard for the determination of the erythrocyte
sedimentation rate (ESR) is the Westergren method. Other methods to measure the
ESR have become available. They range from modest modifications of the Westergren
method to very different methodologies. The ICSH therefore established a Working
Group to investigate these new approaches and compile recommendations for their
validation and verification. METHODS: A panel of six experts in laboratory
hematology examined the peer-reviewed literature and EQA surveys from over 6000
laboratories on four continents performing ESR testing. This information was used
to create lists of ESR instrument manufacturers and their methods. RESULTS: Only
28% of laboratories surveyed used the unmodified Westergren method, while 72% of
sites used modified or alternate methods. Results obtained with the new
instruments could differ from results obtained with the Westergren method by up
to 142%. Different non-Westergren methods showed differences from each other of
up to 42%. The new methods were often significantly faster, safer, and less labor
intensive. They reduced costs and often used standard EDTA tubes, eliminating the
need for a dedicated ESR tube. CONCLUSION: Based on the consensus of the Working
Group, recommendations for manufacturers for the validation of new ESR methods
were developed. In addition, a list of recommendations for laboratories that are
moving to modified or alternate methods was compiled, addressing instrument
performance verification and communications of results to clinical users.
PMID- 28497538
TI - Multimodality imaging of a left ventricular aneurysm in a patient with normal
coronary arteries: Unusual localization.
AB - Left ventricular aneurysm (LVA) is rare but potentially fatal complication of
myocardial infarction. It has been strictly defined as a distinct area of
abnormal left ventricular diastolic contour with systolic dyskinesia or
paradoxical bulging. It may be asymptomatic. However, complications including
thromboembolism, heart failure, valvular regurgitation, arrhythmia, and rarely
rupture may be the initial presentation. Diagnosis may be established by
transthoracic echocardiography, left ventriculography, computed tomographic
angiography, and cardiac magnetic resonance imaging. Here, we report a case of
uncommonly located LVA in an adult patient with normal coronary arteries, which
was diagnosed with multimodality imaging.
PMID- 28497539
TI - Inverse-Electron-Demand Diels-Alder Reactions: Principles and Applications.
AB - Inverse-electron-demand Diels-Alder (iEDDA) reactions are an intriguing class of
cycloaddition reactions that have attracted increasing attention for their
application in bioorthogonal chemistry, the total synthesis of natural products,
and materials science. In many cases, the application of the iEDDA reaction has
been demonstrated as an innovative approach to achieve target structures. The
theoretical aspects of this class of reactions are of particular interest for
scientists as a means to understand the various factors, such as steric strain
and electron density of the attached groups, that govern the reaction and thus to
elucidate the reaction mechanism. This review aims to summarize both theoretical
investigations and application-driven research work on the iEDDA reaction. First,
the historical aspects and the theoretical basis of the reaction, especially
recent advances in time-dependent density functional theory (TD-DFT)
calculations, as well as catalysis strategies will be highlighted and discussed.
Second, the applications of this novel reaction in the context of materials
science, bioorthogonal chemistry, and total synthesis of natural products will be
elaborated with selected recent examples. The challenges and opportunities of the
iEDDA reaction will be highlighted to give more insight into its potential
applications in many other research areas.
PMID- 28497540
TI - Meikin-associated polo-like kinase specifies Bub1 distribution in meiosis I.
AB - In meiosis I, sister chromatids are captured by microtubules emanating from the
same pole (mono-orientation), and centromeric cohesion is protected throughout
anaphase. Shugoshin, which is localized to centromeres depending on the
phosphorylation of histone H2A by Bub1 kinase, plays a central role in protecting
meiotic cohesin Rec8 from separase cleavage. Another key meiotic kinetochore
factor, meikin, may regulate cohesion protection, although the underlying
molecular mechanisms remain elusive. Here, we show that fission yeast Moa1
(meikin), which associates stably with CENP-C during meiosis I, recruits Plo1
(polo-like kinase) to the kinetochores and phosphorylates Spc7 (KNL1) to
accumulate Bub1. Consequently, in contrast to the transient kinetochore
localization of mitotic Bub1, meiotic Bub1 persists at kinetochores until
anaphase I. The meiotic Bub1 pool ensures robust Sgo1 (shugoshin) localization
and cohesion protection at centromeres by cooperating with heterochromatin
protein Swi6, which binds and stabilizes Sgo1. Furthermore, molecular genetic
analyses show a hierarchical regulation of centromeric cohesion protection by
meikin and shugoshin that is important for establishing meiosis-specific
chromosome segregation. We provide evidence that the meiosis-specific Bub1
regulation is conserved in mouse.
PMID- 28497541
TI - The impact of body weight on the diagnosis of aortic dilation-misdiagnosis in
overweight and underweight groups.
AB - BACKGROUND: Body surface area (BSA)-indexed Z-scores are used to assess the
ascending aorta (AAo) and diagnose aortic dilation (AoD) in children. BSA is
directly related to body weight and corresponds to body mass index (BMI). We
hypothesized extremes in BMI alter interpretation of aortic size in pediatric
patients with AoD. METHODS: We reviewed all echocardiograms with a diagnosis of
AoD performed at our institution from January 2013 through June 2013. Those with
an age <2 or >20 years, history of aortic root surgery, or inadequate images were
excluded. The aorta was measured by standard methods at the sinus of Valsalva,
sinotubular junction, and proximal AAo. Using subject age, height, and gender,
hypothetical weights for each subject were calculated to provide BMIs
corresponding to the 5th, 50th, 85th, and 95th percentiles. The derived weights
were then used to determine hypothetical BSA, and Z-scores were calculated for
the subject's aortic diameters in each BMI group. RESULTS: A total of 153
patients met inclusion criteria. Mean age was 11.1+/-4.6 years (68% male). Mean
height was 142.7+/-27.9 cm, mean weight 44.6+/-24.8 kg, and mean true BMI was the
62nd centile. Significant differences in all aortic dimension Z-scores were found
among normal and underweight, overweight, and obese BMI groups (P<.001 for all
comparisons), respectively. CONCLUSION: Using current recommended methods, AoD
will be missed in overweight and obese patients and overdiagnosed in underweight
patients. For children of normal weight, a Z-score based on BSA may be reliable.
As obesity rates increase, weight-independent Z-scores must be developed.
PMID- 28497542
TI - Molecular detection and phylogenetic analysis of hepatitis E virus strains
circulating in wild boars in south-central Italy.
AB - Hepatitis E virus (HEV) is a zoonotic pathogen with a worldwide distribution, and
infects several mammalian species, including pigs and wild boars, which are
recognized as its natural reservoirs. The virus causes a usually self-limiting
liver disease with a mortality rate generally below 1%, although mortality rates
of 15%-25% have been recorded in pregnant woman. Chronic infections can also
occur. The prevalence of HEV has been extensively studied in wild boars and pigs
in northern Italy, where intensive pig herds are predominantly located. In
contrast, few data have been collected in south-central Italy, where small pig
herds are surrounded by large regional parks populated with heterogeneous wild
fauna. In this study, 291 liver samples from wild boars caught in south-central
Italy were analysed with the molecular detection of viral RNA. Our results
confirm the circulation of HEV in these animals, with a mean prevalence of 13.7%
(40 of 291). A nucleotide sequence analysis showed that the HEV strains were
highly conserved within the same geographic areas. The wild boar HEV strains
belonged to the HEV-3c subtype, which is frequently described in wild boars, and
to an uncommon undefined subtype (HEV-3j-like).The viral prevalence detected is
concerning because it could represent a potential risk to hunters, meat workers
and consumers of wild boar liver and derivative products. The hypothesized inter
species transmission of HEV to pigs and the possibility that the virus maintains
its virulence in the environment and the meat chain also present potential risks
to human health, and warrant further investigations in the near future.
PMID- 28497543
TI - Critical values in hematology of 862 institutions in China.
AB - INTRODUCTION: A national survey on critical values in hematology of China
laboratories was conducted to determine the current practice and assess the
quality indicators so as to obtain a quality improvement. METHODS: Laboratories
participating were asked to submit the general information, the practice of
critical value reporting, and the status of timeliness of critical value
reporting. RESULTS: A total of 862 laboratories submitted the results. The
majority of participants have included white blood cell count, blood platelet
count, hemoglobin, prothrombin time, and activated partial thromboplastin time in
their critical value lists. Many sources are used for establishing a critical
value policy, and some of the laboratories consult with clinicians. The
unreported critical value rate, late critical value reporting rate, and
clinically unacknowledged rate in China are relatively low, and the median of
critical value reporting time is 8-9 minutes. CONCLUSION: There exists a wide
variety for critical value reporting in hematology in China. Laboratories should
establish a policy of critical value reporting suited for their own situations
and consult with clinicians to set critical value lists. Critical values are
generally reported in a timely manner in China, but some measures should be taken
to further improve the timeliness of critical value reporting.
PMID- 28497544
TI - Inducing unconscious stress: Cardiovascular activity in response to subliminal
presentation of threatening and neutral words.
AB - Stress-related cognitive processes may occur outside of awareness, here referred
to as unconscious stress, and affect one's physiological state. Evidence
supporting this idea would provide necessary clarification of the relationship
between psychological stress and cardiovascular (CV) health problems. We tested
the hypothesis that increases in mean arterial pressure (MAP) and total
peripheral resistance (TPR) and decreases in heart rate variability (HRV) would
be larger when threatening stimuli are presented outside of awareness, or
subliminally, compared with neutral stimuli. Additionally, it was expected that
trait worry and resting HRV, as common risk factors for CV disease, would
moderate the effect. We presented a subliminal semantic priming paradigm to
college students that were randomly assigned to the threat (n = 56) or neutral
condition (n = 60) and assessed changes from baseline of MAP, TPR, and HRV. Level
of trait worry was assessed with the Penn State Worry Questionnaire. The findings
indicate that CV activity changed according to the hypothesized pattern: A higher
MAP and TPR and a lower HRV in the threat condition compared with the neutral
condition were found with practically meaningful effect sizes. However, these
findings were only statistically significant for TPR. Furthermore, changes in CV
activity were not moderated by trait worry or resting HRV. This is the first
study to explicitly address the role of subliminally presented threat words on
health-relevant outcome measures and suggests that unconscious stress can
influence peripheral vascular resistance.
PMID- 28497545
TI - Milk protein synthesis is regulated by T1R1/T1R3, a G protein-coupled taste
receptor, through the mTOR pathway in the mouse mammary gland.
AB - SCOPE: Understanding the regulatory mechanism of milk protein synthesis is
important to develop strategies to improve milk protein and enhance lactation
performance. The mammalian target of rapamycin (mTOR) pathway is a crucial
modulator of protein synthesis. In this study, we want to investigate if
T1R1/T1R3 can regulate milk protein synthesis and mediate the mTOR pathway in the
mice mammary gland in vivo. METHODS AND RESULTS: T1R1 knockout mice, WT mice, and
mammary explants were used. The weigh-suckle-weigh method was used to quantify
the milk yield. The expression level of beta-casein and AA transporter mRNA were
analyzed by qPCR. Western blot was used to analyze protein abundance of members
of the mTOR pathway. As expected, the knockout of T1R1 not only reduced the total
milk yield in the mice mammary glands, but also repressed beta-casein synthesis.
Additionally, the phosphorylation of 4EBP1 and S6K was significantly decreased in
T1R1 knockout mice. The T1R1 knockout also increased the protein abundance of the
AA transporter SLC3A2 and mRNA expression of SLC7A5/SLC3A2 and SLC1A5. Activation
of the mTOR pathway was repressed by inhibition of T1R3 or T1R1 knockout in
mammary gland explants. CONCLUSION: T1R1/T1R3 modulates the mTOR pathway to
regulate milk protein synthesis in the mouse mammary gland in vivo.
PMID- 28497546
TI - An error in the article by Oteri et al: 'Prescribing pattern of antipsychotic
drugs during the years 1996-2010'.
PMID- 28497548
TI - Erratum.
PMID- 28497549
TI - A large scale prospective clinical and psychometric validation of the EORTC
colorectal (QLQ-CR29) module in Polish patients with colorectal cancer.
AB - The purpose of our study was to assess if the Polish translation of the European
Organisation for Research and Treatment of Cancer (EORTC) Colorectal Cancer (CRC)
Specific Quality of Life Questionnaire (QLQ-CR29) is an acceptable and
psychometrically valid measure to collect quality of life (QoL) data in Polish
patients with CRC for use in clinical trials and clinical practice. A total of
150 patients undergoing treatment for CRC were prospectively enrolled in the
study. Psychometric assessment of the translated QLQ-CR29 structure, reliability,
convergent and divergent validity, and clinical validity was subsequently
performed. The Cronbach's alpha coefficient ranged from 0.70-0.89, indicating
acceptable internal consistency. For test-retest reliability, the ICCs for each
item ranged from 0.59-0.91, with exceptions for urinary incontinence and dysuria,
indicating good to excellent reproducibility. In multi-trait scaling analyses,
the criterion for item convergent and divergent validity was satisfied. The
correlations between the EORTC QLQ-CR29 and QLQ-C30 scales were mostly low (r <
.40), with a few items demonstrating higher correlations. The known group
comparisons analyses demonstrated the ability of the questionnaire to distinguish
between patients' differing age, stoma status, and treatment intent. The Polish
translation of the QLQ-CR29 is a psychometrically reliable and valid tool. The
results of this study are congruent with that of EORTC validation.
PMID- 28497551
TI - Proximity and gravity: modeling heaped self-reports.
AB - Self-reported daily cigarette counts typically exhibit a preponderance of round
numbers, a phenomenon known as heaping or digit preference. Heaping can be a
substantial nuisance, as scientific interest lies in the distribution of the
underlying true values rather than that of the heaped data. In principle, we can
estimate parameters of the underlying distribution from heaped data if we know
the conditional distribution of the heaped count given the true count, denoted
the heaping mechanism (analogous to the missingness mechanism for missing data).
In general, it is not possible to estimate the heaping mechanism robustly from
heaped data only. A doubly-coded smoking cessation trial data set that includes
daily cigarette count as both a conventional heaped retrospective recall
measurement and a precise instantaneous measurement offers the rare opportunity
to directly estimate the heaping mechanism. We propose a novel model that
describes the conditional probability of the self-reported count as a function of
its proximity to the truth and its intrinsic attractiveness, denoted its gravity.
We apply variations of the model to the cigarette count data, illuminating the
cognitive processes that influence self-reporting behaviors. The principal
application of the model will be to enabling the correct analysis of heaped-only
data sets. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28497550
TI - Metagenomics analysis of red blood cell and fresh-frozen plasma units.
AB - BACKGROUND: Although the risk of transmitting infectious agents by blood
transfusion is dramatically reduced after donor selection, leukoreduction, and
laboratory testing, some could still be present in donor's blood. A description
of metagenomes in blood products eligible for transfusion represents relevant
information to evaluate the risk of pathogen transmission by transfusion. STUDY
DESIGN AND METHODS: Detection of viruses, bacteria, and fungi genomes was made by
high-throughput sequencing (HTS) of 600 manufactured blood products eligible for
transfusion: 300 red blood cell (RBC) and 300 fresh-frozen plasma (FFP) units.
RESULTS: Anelloviruses and human pegivirus, frequent in the blood of healthy
individuals, were found. Human papillomavirus type 27 and Merkel cell
polyomavirus, present on the skin, were also detected. Unexpectedly, astrovirus
MLB2 was identified and characterized in a FFP unit. The presence of astrovirus
MLB2 was confirmed in donor's blood and corresponded to an asymptomatic acute
viremia. Sequences of bacteria and fungi were also detected; they are likely the
result of environmental contamination. CONCLUSION: This study demonstrates that
HTS is a promising tool for detecting common and less frequent infectious
pathogens in blood products.
PMID- 28497552
TI - A novel porcine kobuvirus emerged in piglets with severe diarrhoea in China.
AB - Since the first report of porcine kobuvirus (PKV) in 2008, it has been confirmed
that PKV is widely present in several countries and plays an important role in
diarrhoea outbreak in pigs. Studies have shown that the biggest difference among
PKVs is the presence or absence of a specific 30-amino acid (aa) sequence in the
2B region of the polyprotein gene. Based on this unique feature, most PKV
sequences could be divided into two groups (Group 1 without deletion and Group 2
with deletion), but a few sequences did not follow this rule due to possible
recombination. In this study, two PKV genome sequences, designated JXAT2015
(8,123 nucleotide) and JXJC2015 (8,120 nucleotide), were identified on two
different commercial swine farms with the severe diarrhoea outbreak accompanying
with highly PKV infection (90%, 18/20) and moderate infection (40%, 8/20) of
porcine bocavirus 1 (PBoV1) in Jiangxi province of China. Sequence analysis based
on the polyprotein gene showed that they shared low nucleotide similarity (86.3%
88.1%) with other known PKVs. Although both possessed the 30-aa deletion in the
2B region, phylogenetic analysis showed that JXJC2015 was distinct from Group 1
and even Group 2, and formed a new Group (designated Group 3). The findings of
this study further revealed genetic diversity and the possible pathogenic role of
PKV in conjunction with other pathogens in piglets.
PMID- 28497553
TI - Simultaneous transcatheter therapy for perimembranous ventricular septal defect
combined with patent ductus arteriosus.
AB - OBJECTIVE: This study aims to assess the clinical efficiency and safety of
simultaneous transcatheter interventional treatment for perimembranous
ventricular septal defect (pmVSD) combined with patent ductus arteriosus (PDA).
METHODS: Twenty-five patients with pmVSD and PDA treated with simultaneous
transcatheter interventions from April 2004 to December 2015 were included in
this study. The mean age was 9.80 +/- 8.14 years and the mean weight was 29.76 +/
14.82 Kg. Transthoracic echocardiography (TTE) and angiography were performed
immediately after the procedure. Patients were re-examined by electrocardiogram,
X-ray, and TTE at 2 days, 1 month, 3 months, and 6 months postoperatively.
RESULTS: The interventional procedure was successfully performed in all 25
patients. No intraoperative complication was noted. TTE examination of the VSD
and PDA immediately after the procedure showed no residual shunt and the occluder
was well positioned. Among these patients, four patients showed electrocardiogram
changes after the procedure that resolved after drug therapy. The cardiothoracic
ratio, left atrial diameter, left ventricular end-systolic diameter, and left
ventricular end-diastolic diameter recovered to normal in most patients at 6
months postoperatively. CONCLUSIONS: Simultaneously transcatheter interventional
therapy is a safe and effective method for pmVSD combined with PDA.
PMID- 28497555
TI - Multifunctional Free-Standing Gel Polymer Electrolyte with Carbon Nanofiber
Interlayers for High-Performance Lithium-Sulfur Batteries.
AB - Free-standing trimethylolpropane ethoxylate triacrylate gel polymer electrolyte
is synthesized by a chemical cross-linking process and used as an electrolyte and
separator membrane in lithium-sulfur batteries. The cross linked gel polymer
electrolyte also exhibited a stable geometric size retention of 95 % at the high
temperature of 130 degrees C. The as-prepared gel polymer electrolyte membrane
with carbon nanofibers interlayer can effectively prevent polysulfide dissolution
and shuttle effect, leading to significantly enhanced electrochemical properties,
including high capacity and cycling stability, with an enhanced specific capacity
of 790 mA h g-1 after 100 cycles.
PMID- 28497554
TI - Shaking Up the Debate: Ensuring the Ethical Use of DBS Intervention Criteria for
Mid-Stage Parkinson's Patients.
AB - OBJECTIVES: Deep brain stimulation (DBS) is a well-established treatment for the
management of severe motor fluctuations in advanced Parkinson's disease (PD).
Until recently, device regulation, medical, and insurance practices limited DBS
to patients with advanced stages of PD. In February 2016 this changed, however,
when the US Food and Drug Administration (FDA) granted formal approval for the
use of brain stimulator in mid-stage PD patients. In this article, we examine
whether DBS in mid-stage PD can be ethically justified beyond the FDA approval.
MATERIALS AND METHODS: We scrutinize the current risk-benefit profile, the costs
benefit profile, and the capacity for informed consent requirement, to ask if use
of subthalamic nucleus (STN) in mid-stage DBS is ethically appropriate. RESULTS:
We propose that mid-stage DBS decisions could be appropriate under a shared
decision-making model, which embraces a broad quality of life perspective.
CONCLUSION: Although it might be too premature to know how the FDA decision will
affect medical and insurance practices, we conclude by arguing that revisions to
persisting guidelines seems justified both on scientific and ethical grounds.
PMID- 28497556
TI - Mitral arcade: A rare case presenting with fatigue and cough.
AB - An 11-year-old girl was admitted to pediatric emergency unit with complaints of
fatigue and cough. The patient had no previous complaints. There was no history
of rheumatic heart disease. The height and duration of the P-wave was 4 mm and
0.16 seconds, respectively (p mitrale). Echocardiography showed enlarged left
atrium (51*61 mm in diameter). Both the anterolateral and posteromedial papillary
muscles were directly attached to the anterior and posterior mitral valve
leaflets without tendinous chords. The patient was diagnosed with mitral arcade,
severe mitral stenosis, and mitral regurgitation. The patient was referred to
surgery for replacement of mitral valve.
PMID- 28497557
TI - Acquiring research-grade ERPs on a shoestring budget: A comparison of a modified
Emotiv and commercial SynAmps EEG system.
AB - This study compared the performance of a low-cost wireless EEG system to a
research-grade EEG system on an auditory oddball task designed to elicit N200 and
P300 ERP components. Participants were 15 healthy adults (6 female) aged between
19 and 40 (M = 28.56; SD = 6.38). An auditory oddball task was presented
comprising 1,200 presentations of a standard tone interspersed by 300 trials
comprising a deviant tone. EEG was simultaneously recorded from a modified Emotiv
EPOC and a NeuroScan SynAmps RT EEG system. The modifications made to the Emotiv
system included attaching research grade electrodes to the Bluetooth transmitter.
Additional modifications enabled the Emotiv system to connect to a portable
impedance meter. The cost of these modifications and portable impedance meter
approached the purchase value of the Emotiv system. Preliminary analyses revealed
significantly more trials were rejected from data acquired by the modified Emotiv
compared to the SynAmps system. However, the ERP waveforms captured by the Emotiv
system were found to be highly similar to the corresponding waveform from the
SynAmps system. The latency and peak amplitude of N200 and P300 components were
also found to be similar between systems. Overall, the results indicate that, in
the context of an oddball task, the ERP acquired by a low-cost wireless EEG
system can be of comparable quality to research-grade EEG acquisition equipment.
PMID- 28497558
TI - Ectopic thyroid mass in the right ventricle: A case report.
AB - Ectopic thyroid is a rare congenital embryonic anomaly. Ectopic thyroid tissue
can be located anywhere during its descent, but it is found primarily at the base
of the tongue and in the mediastinum. It is very rarely found in the heart. Here,
we report a rare case of cardiac ectopic thyroid tissue in a 53-year-old woman
who presented with chest pain. Echocardiography revealed an intracardiac mass
that was removed successfully. Histopathology confirmed that the mass was thyroid
tissue without malignancy.
PMID- 28497559
TI - Macromolecular structures: Quality assessment and biological interpretation.
AB - Structure determination using X-ray crystallography involves collection of
diffraction data, determination of initial phases followed by iterative rounds of
model building and crystallographic refinement to improve the phases and minimize
the differences between calculated and observed structure factors. At each of
these stages, a variety of statistical filters exist to ensure appropriate
validation. Biologically important observations often come from interpretations
of signals that need to be carefully deciphered from noise, and therefore human
intervention is as important as the automated methods and filters. Currently, all
structural data are deposited in the Protein Data Bank (PDB), and this repository
is continuously evolving to incorporate new developments in macromolecular
crystallography. The journals that publish data arising from structural studies
modulate their policies to take cognizance of new improved methodologies.
Together, the PDB and journals have evolved an accepted protocol to ensure the
integrity of crystallographic results. As a result, the quality of available data
and associated interpretations have improved over the years. Typically, if there
are differences regarding the mechanism of action of a protein revealed by
crystallography then new experiments are carried out to provide further evidence
for or against a particular hypothesis. Hence, the scientific systems in
structural biology are robust and to a large extent capable of correcting any
errors in interpretation of structural results. However, this process is hindered
by spurious challenges to published research, based on misuse of validation
mechanisms. Such activities are counterproductive and will cause damage to the
field of structural biology. (c) 2017 IUBMB Life, 69(8):563-571, 2017.
PMID- 28497560
TI - Untargeted Metabolomic Analysis of Capsicum spp. by GC-MS.
AB - INTRODUCTION: In order to conserve the biodiversity of Capsicum species and find
genotypes with potential to be utilised commercially, Embrapa Clima Temperado
maintains an active germplasm collection (AGC) that requires characterisation,
enabling genotype selection and support for breeding programmes. OBJECTIVE: The
objective of this study was to characterise pepper accessions from the Embrapa
Clima Temperado AGC and differentiate species based on their metabolic profile
using an untargeted metabolomics approach. MATERIAL AND METHODS: Cold (-20
degrees C) methanol extraction residue of freeze-dried fruit samples was
partitioned into water/methanol (A) and chloroform (B) fractions. The polar
fraction (A) was derivatised and both fractions (A and B) were analysed by gas
chromatography coupled to mass spectrometry (GC-MS). Data from each fraction was
analysed using a multivariate principal component analysis (PCA) with XCMS
software. RESULTS: Amino acids, sugars, organic acids, capsaicinoids, and
hydrocarbons were identified. Outlying accessions including P116 (C. chinense),
P46, and P76 (C. annuum) were observed in a PCA plot mainly due to their high
sucrose and fructose contents. PCA also indicated a separation of P221 (C.
annuum) and P200 (C. chinense), because of their high dihydrocapsaicin content.
CONCLUSIONS: Although the metabolic profiling did not allow for grouping by
species, it permitted the simultaneous identification and quantification of
several compounds complementing and expanding the metabolic database of the
studied Capsicum spp. in the AGC. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28497561
TI - On assessing bioequivalence and interchangeability between generics based on
indirect comparisons.
AB - As more and more generics become available in the market place, the
safety/efficacy concerns may arise as the result of interchangeably use of
approved generics. However, bioequivalence assessment for regulatory approval
among generics of the innovative drug product is not required. In practice,
approved generics are often used interchangeably without any mechanism of safety
monitoring. In this article, based on indirect comparisons, we proposed several
methods to assessing bioequivalence and interchangeability between generics. The
applicability of the methods and the similarity assumptions were discussed, as
well as the inappropriateness of directly adopting adjusted indirect comparison
to the field of generics' comparison. Besides, some extensions were given to take
into consideration the important topics in clinical trials for bioequivalence
assessments, for example, multiple comparisons and simultaneously testing
bioequivalence among three generics. Extensive simulation studies were conducted
to investigate the performances of the proposed methods. The studies of malaria
generics and HIV/AIDS generics prequalified by the WHO were used as real examples
to demonstrate the use of the methods. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28497562
TI - Different aggregation states of a nuclear localization signal-tagged 25-kDa C
terminal fragment of TAR RNA/DNA-binding protein 43 kDa.
AB - The mechanism and cause of motor neuronal cell death in amyotrophic lateral
sclerosis (ALS), a devastating neurodegenerative disorder, are unknown; gain of
function of oligomers and aggregation of misfolded proteins, including carboxyl
terminal fragments (CTFs) of TAR RNA/DNA-binding protein 43 kDa (TDP-43), have
been proposed as important causative factors in the onset of ALS. We recently
reported that a nuclear localization signal (NLS)-tagged 25-kDa CTF of TDP-43
(TDP25) could decrease the cell-death proportion compared with that promoted by
TDP25. Here, we show oligomeric states of NLS-TDP25 and its detailed localization
property using super-resolution fluorescence microscopy, FRET, fluorescence
recovery after photobleaching, and fluorescence correlation spectroscopy
analysis. NLS-TDP25 efficiently formed a nucleolar cap structure via RNA binding
in the presence of actinomycin D, but TDP25 did not. Although cytoplasmic
inclusion bodies including TDP25 had a disordered and immobile structure, NLS
TDP25 in the nucleolus was ordered and dynamic. In the diffuse state, TDP25
formed fewer oligomers and interacted with the molecular chaperone, HSP70;
however, NLS-TDP25 formed oligomers. These results suggested that NLS-tagged
TDP25 can change its structure to use ordered oligomeric but nontoxic state.
Moreover, the structure of ordered oligomers as well as nuclear sequestration may
be important in mediating cytotoxicity in ALS pathology.
PMID- 28497563
TI - Frequency of polycythemia in individuals with normal complete blood cell counts
according to the new 2016 WHO classification of myeloid neoplasms.
AB - INTRODUCTION: Polycythemia vera (PV) is a disorder characterized by clonal
proliferation of myeloid cells and increased red blood cell mass. Recently, the
revised 2016 WHO classification of myeloid neoplasms decreased the threshold
levels of hemoglobin and hematocrit for the diagnosis of PV. However, the new
proposed cutoffs have remarkable overlap with the normal reference values
reported and the clinical impact of these new cutoffs has not been widely
assessed in the general population. METHODS: We retrospectively examined 248 839
patients with presumptively normal complete blood cell results, consecutively
obtained in an outpatient setting. RESULTS: The proportion of men with Hb >165
g/L was 5.99%, Hct>49% was 2.4%, and Hb >165 g/dL or Hct>49% was 6.48%, while the
proportion of women with Hb >160 g/L was 0.22%, Hct>48% was 0.11%, and Hb >160
g/L or Hct>48% was 0.28%. CONCLUSION: The isolated use of the proposed Hb/Hct
levels as a definer of polycythemia may lead to a substantial increase in
unnecessary diagnostic tests. In cases with borderline levels of hemoglobin, the
diagnostic workup of PV should only be indicated in the presence of clinical
and/or laboratorial features associated with MPN.
PMID- 28497565
TI - Transient left ventricular outflow tract obstruction with systolic anterior
motion of the mitral valve: A stunning cause.
AB - Left ventricular outflow tract obstruction (LVOTO) and systolic anterior motion
(SAM) of the mitral valve may have various etiologies, of which hypertrophic
cardiomyopathy is the most common. More rarely, an acute coronary syndrome,
myocardial stunning, and takotsubo cardiomyopathy may give rise to LVOTO and SAM.
Here, we present a 70-year-old female patient with a non-ST-elevation acute
coronary syndrome treated with percutaneous coronary intervention.
Echocardiography the day after, because of dyspnea and hypotension, revealed
apical akinesia, LVOTO, and SAM, which proved completely reversible after
treatment with a beta-blocker and a 2-month follow-up period. It was concluded
that postischemic apical stunning had caused LVOTO and SAM.
PMID- 28497564
TI - No significant enrichment of rare functionally defective CPA1 variants in a large
Chinese idiopathic chronic pancreatitis cohort.
AB - Rare functionally defective carboxypeptidase A1 (CPA1) variants have been
reported to predispose to nonalcoholic chronic pancreatitis, mainly the
idiopathic subtype. However, independent replication has so far been lacking,
particularly in Asian cohorts where initial studies employed small sample sizes.
Herein we performed targeted next-generation sequencing of the CPA1 gene in 1,112
Han Chinese idiopathic chronic pancreatitis (ICP) patients-the largest ICP cohort
so far analyzed in a single population-and 1,580 controls. Sanger sequencing was
used to validate called variants, and the CPA1 activity and secretion of all
newly found variants were measured. A total of 18 rare CPA1 variants were
characterized, 11 of which have not been previously described. However, no
significant association was noted with ICP irrespective of whether all rare
variants [20 out of 1,112 (1.8%) in patients vs. 24 out of 1,580 (1.52%) in
controls; P = 0.57] or functionally impaired variants [three out of 1,112 (0.27%)
in patients vs. two out of 1,580 (0.13%) in controls; P = 0.68] were considered.
PMID- 28497566
TI - CEST MRI of 3-O-methyl-D-glucose on different breast cancer models.
AB - PURPOSE: To test the ability of chemical exchange saturation transfer (CEST) MRI
of 3-O-methyl-D-glucose (3OMG) to detect tumors in several breast cancer models
of murine and human origin, for different routes of administration of the agent
and to compare the method with glucoCEST and with 18 FDG-PET on the same animals.
METHODS: In vivo CEST MRI experiments were performed with a 7T Biospec animal MRI
scanner on implanted orthotopic mammary tumors of mice before and after
administration of 3OMG. RESULTS: A marked 3OMG-CEST MRI contrast that was
correlated with the administrated dose was obtained in different breast cancer
models and by intravenous, intraperitoneal, and per os methods of administration.
The most aggressive breast cancer model yielded the highest CEST contrast. 3OMG
CEST contrast reached its maximum at 20 min after administration and lasted for
more than an hour, while that of glucose was lower and diminished after 20 min.
3OMG-CEST showed comparable results to that of FDG PET. CONCLUSION: The
sensitivity of the 3OMG-CEST MRI method indicates its potential for the detection
of tumors in the clinic. Magn Reson Med 79:1061-1069, 2018. (c) 2017
International Society for Magnetic Resonance in Medicine.
PMID- 28497567
TI - Determination of disease phenotypes and pathogenic variants from exome sequence
data in the CAGI 4 gene panel challenge.
AB - The use of gene panel sequence for diagnostic and prognostic testing is now
widespread, but there are so far few objective tests of methods to interpret
these data. We describe the design and implementation of a gene panel sequencing
data analysis pipeline (VarP) and its assessment in a CAGI4 community experiment.
The method was applied to clinical gene panel sequencing data of 106 patients,
with the goal of determining which of 14 disease classes each patient has and the
corresponding causative variant(s). The disease class was correctly identified
for 36 cases, including 10 where the original clinical pipeline did not find
causative variants. For a further seven cases, we found strong evidence of an
alternative disease to that tested. Many of the potentially causative variants
are missense, with no previous association with disease, and these proved the
hardest to correctly assign pathogenicity or otherwise. Post analysis showed that
three-dimensional structure data could have helped for up to half of these cases.
Over-reliance on HGMD annotation led to a number of incorrect disease
assignments. We used a largely ad hoc method to assign probabilities of
pathogenicity for each variant, and there is much work still to be done in this
area.
PMID- 28497568
TI - Neuropsychological phenotypes of 76 individuals with Joubert syndrome evaluated
at a single center.
AB - Joubert syndrome (JS) is a genetically heterogeneous ciliopathy characterized by
hypo-dysplasia of the cerebellar vermis, a distinct hindbrain/midbrain
malformation (molar tooth sign), and intellectual disability. We evaluated the
neuropsychological profiles of 76 participants with JS in the context of
molecular genetics and clinical covariates. Evaluations included
neuropsychological testing, structured parental interviews, DNA sequencing, brain
magnetic resonance imaging (MRI), electroencephalography (EEG), ophthalmologic
examination, and assessment for renal and hepatic disease. On average,
participants manifested Full Scale Intelligence Quotients (FSIQ) in the
moderately to profoundly low range (M = 64.3 +/- 15.3). Of the Wechsler index
scores, verbal comprehension was least affected and processing speed was most
affected. Receptive language was rated as better than expressive language on the
Vineland Adaptive Behavior Scales-Second Edition. Those with abnormal EEG had a
significantly lower FSIQ (n = 15; M = 50.7 +/- 12.9) compared to participants
with normal EEG (n = 39; M = 64.7 +/- 16.3; p = .004). Participants taking
psychiatric medications manifested a lower FSIQ (n = 20; M = 54.8 +/- 13.2) than
those not taking them (n = 42; M = 65.0 +/- 17.2; p = .022). These correlations
were also present in the TMEM67-related JS sub-cohort (n = 14). Based on parental
assessment, psychiatric and behavioral problems were significantly more common
than in the general population for all measures (p < .004 for all). The majority
(65%) of individuals with JS have some degree of intellectual disability.
Abnormal EEG is associated with lower neuropsychological function. Processing
speed is a weakness, while verbal comprehension and receptive language are
relative strengths. These findings may guide parents, teachers, therapists, and
doctors to determine appropriate therapies, accommodations, and academic goals
for individuals with JS.
PMID- 28497569
TI - Early Onset of Efficacy and Consistency of Response Across Multiple Migraine
Attacks From the Randomized COMPASS Study: AVP-825 Breath Powered(r) Exhalation
Delivery System (Sumatriptan Nasal Powder) vs Oral Sumatriptan.
AB - OBJECTIVE: To further characterize the clinical utility of AVP-825 based on
additional prespecified outcomes and post hoc analyses of COMPASS, a Phase 3
comparative efficacy trial of AVP-825 vs 100 mg oral sumatriptan (NCT01667679).
AVP-825 was approved in January 2016 by the US Food and Drug Administration under
the name ONZETRA(r) Xsail(r) (sumatriptan nasal powder) for the acute treatment
of migraine with or without aura in adults. BACKGROUND: AVP-825 is a delivery
system that uses a patient's own breath to deliver low-dose sumatriptan powder to
the upper posterior regions of the nasal cavity beyond the narrow nasal valve,
areas lined with vascular mucosa conducive to rapid drug absorption into the
systemic circulation. The recommended dose of AVP-825 is 22 mg sumatriptan powder
administered as one 11 mg nosepiece in each nostril, which delivers approximately
15-16 mg of sumatriptan intranasally. The COMPASS trial compared AVP-825 22-100
mg oral sumatriptan across multiple migraine attacks for efficacy, safety, and
tolerability endpoints. DESIGN/METHODS: COMPASS was a randomized, multicenter,
double-dummy, crossover, multiattack, comparative efficacy study with two 12-week
double-blind periods. Patients with 2-8 migraine attacks/month were randomized
1:1 to AVP-825 (22 mg) plus oral placebo or an identical placebo delivery system
plus 100 mg oral sumatriptan for the first period, and then patients switched
treatments for the second period. Patients treated up to 5 qualifying migraines
per period within 1 h of onset, even if the intensity of the attack was mild.
Results from the primary endpoint (SPID-30, defined as the sum of pain intensity
differences from dosing to 30 minutes), key secondary efficacy endpoints and
safety assessments have been reported in the primary publication (Tepper et al.,
2015). This article reports additional prespecified outcomes, including the SPID
30 for attacks treated when baseline severity was mild vs moderate/severe,
measures of sustained response and consistency of effect in patients who
experienced multiple migraine attacks, and the results of post hoc analyses
performed to assess total migraine freedom (defined as no pain and no migraine
associated symptoms, including nausea, vomiting, photophobia, and phonophobia),
time to pain freedom, time to meaningful pain relief, and local (occurring at the
site of administration in the nose) vs systemic treatment-emergent adverse events
(TEAEs). RESULTS: A total of 185 patients completed both treatment periods,
yielding 1,531 migraine attacks which were treated and assessed (765 AVP-825, 766
oral sumatriptan). Treatment with AVP-825 provided greater reduction in migraine
pain intensity which was statistically significant vs oral sumatriptan in the
first 30 minutes postdose regardless of whether attacks were treated when pain
was mild (least squares mean SPID-30 = 3.90 vs 0.24, P = .0013) or
moderate/severe (least squares mean SPID-30 = 13.83 vs 10.07, P = .0002). At
every time point from 15 to 90 minutes postdose, the proportion of attacks
achieving total migraine freedom was greater and statistically significant after
treatment with AVP-825 vs 100 mg oral sumatriptan. AVP-825 treatment resulted in
greater odds of achieving pain freedom (odds ratio, OR = 1.29, P < .01) and
meaningful pain relief (OR = 1.32, P < .0001), which were also statistically
significant compared with oral sumatriptan. In addition, a greater proportion of
attacks treated with AVP-825 vs oral sumatriptan was associated with sustained
pain freedom, achieving statistical significance when assessed from 1 h postdose
through 24 hours postdose (33.3% vs 27.9%; P < .05) and through 48 hours postdose
(32.7% vs 27.4%; P < .05). For patients who treated multiple migraine attacks in
both treatment periods, a greater proportion had consistent pain relief and pain
freedom following treatment with AVP-825 compared to oral sumatriptan across
multiple attacks, a difference that achieved statistical significance at 30
minutes postdose. Local TEAEs of abnormal taste and nasal discomfort were more
common following AVP-825 treatment. Of the patients experiencing either of these
TEAEs, about 90% described the intensity as mild, and only one discontinued
treatment because of either of these two TEAEs. CONCLUSIONS: These results from
the COMPASS study further demonstrate that treatment with AVP-825 provides
earlier onset and more consistent across-episode improvement of pain and migraine
associated symptoms compared with oral sumatriptan, highlighting the clinical
advantages of this newly approved intranasal delivery system for low-dose
sumatriptan powder.
PMID- 28497570
TI - LAPS Insulin115: A novel ultra-long-acting basal insulin with a unique action
profile.
AB - AIMS: To conduct a comprehensive pre-clinical study of the novel ultra-long
acting insulin analogue LAPS Insulin115. METHODS: Pharmacokinetic/pharmacodynamic
studies comparing LAPS Insulin115 with other basal insulins were conducted in
genetically diabetic (db/db) mice. Insulin signalling in the major target organs
was analysed using Western blot after single subcutaneous injection in wild-type
male Wistar rats. Using in vitro assays we analysed transendothelial transport,
insulin receptor (IR) interaction, and the mitogenic and metabolic properties of
LAPS Insulin115. Furthermore, IR downregulation after long-term exposure to high
concentrations of LAPS Insulin115 was analysed using an in vitro
desensitization/resensitization model. RESULTS: The novel Fc-conjugated insulin
derivative LAPS Insulin115 showed an extensively prolonged pharmacokinetic and
pharmacodynamic profile in rodents. Despite its size of 59 kDa, LAPS Insulin115
passes the vascular endothelial barrier and induces insulin signalling in all
major target tissues in rats. In vitro, LAPS Insulin115 showed a very slow onset
of action because of its reduced IR affinity; however, after long-term
stimulation it was equipotent in respect to its metabolic potency and showed no
increased mitogenic action when compared with regular insulin. Remarkably, under
conditions of chronic exposure, LAPS Insulin115 does not induce irreversible
desensitization of target cells, which is probably attributable to much less
prominent IR downregulation. CONCLUSION: Thus, LAPS Insulin115 exhibits a unique
in vivo and in vitro profile and thereby represents an excellent candidate for a
once-weekly insulin analogue.
PMID- 28497571
TI - Determination of strobilurin fungicide residues in fruits and vegetables by
nonaqueous micellar electrokinetic capillary chromatography with indirect laser
induced fluorescence.
AB - A nonaqueous micellar electrokinetic capillary chromatography method with
indirect LIF was developed for the determination of strobilurin fungicide
residues in fruits and vegetables. Hydrophobic CdTe quantum dots (QDs)
synthesized in aqueous phase were used as background fluorescent substance. The
BGE solution, QD concentration, and separation voltage were optimized to obtain
the best separation efficiency and the highest signal intensity. The optimal BGE
solution consists of 40 mM phosphate, 120 mM sodium dodecyl sulfate, 15% v/v
water and 15% v/v hydrophobic CdTe QDs in formamide, of which apparent pH is 9.5.
The optimized separation voltage is controlled as 25 kV. The resultant detection
limits of azoxystrobin, kresoxim-methyl, and pyraclostrobin are all 0.001 mg/kg,
their linear dynamic ranges are 0.005-2.5 mg/kg, and the recoveries of the spiked
samples are 81.7-96.1%, 86.5-95.7%, and 87.3-97.4%, respectively. This method has
been proved to be sensitive enough to detect the aforementioned fungicides in
fruits and vegetables at the maximum residue limits.
PMID- 28497572
TI - Relationship between red blood cell distribution width, bilirubin, and clinical
characteristics of patients with gastric cancer.
AB - INTRODUCTION: Red blood cell distribution width (RDW) and bilirubin have been
proved to be prognostic factors for various types of cancer. However, their
prognostic value in patients with gastric cancer (GC) remains largely unknown.
METHODS: To verify whether RDW and bilirubin are prognostic factors for patients
with GC, we performed a cross-sectional study to analyze the relationship between
RDW, bilirubin, and the clinical characteristics of patients with GC. Medical
records of all newly diagnosed and pathologically proved patients with GC
admitted to Changzheng Hospital between January 2016 and July 2016 were
retrospectively reviewed. The relationship between RDW, bilirubin, and the
clinical characteristics of patients with GC was analyzed. RESULTS: A total of
144 patients with GC were enrolled. Patients with GC had significantly higher RDW
than healthy controls, even after adjusting for hemoglobin, while total bilirubin
(TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) were significantly
decreased. Furthermore, RDW and bilirubin were significantly correlated with
tumor stage, as well as carcinoembryonic antigen (CEA) and carbohydrate antigen
19-9 (CA19-9). CONCLUSION: Our study indicated that RDW and bilirubin could be
potential prognostic factors for patients of GC.
PMID- 28497573
TI - Simplex-based optimization of numerical and categorical inputs in early
bioprocess development: Case studies in HT chromatography.
AB - Bioprocess development studies often involve the investigation of numerical and
categorical inputs via the adoption of Design of Experiments (DoE) techniques. An
attractive alternative is the deployment of a grid compatible Simplex variant
which has been shown to yield optima rapidly and consistently. In this work, the
method is combined with dummy variables and it is deployed in three case studies
wherein spaces are comprised of both categorical and numerical inputs, a
situation intractable by traditional Simplex methods. The first study employs in
silico data and lays out the dummy variable methodology. The latter two employ
experimental data from chromatography based studies performed with the filter
plate and miniature column High Throughput (HT) techniques. The solute of
interest in the former case study was a monoclonal antibody whereas the latter
dealt with the separation of a binary system of model proteins. The implemented
approach prevented the stranding of the Simplex method at local optima, due to
the arbitrary handling of the categorical inputs, and allowed for the concurrent
optimization of numerical and categorical, multilevel and/or dichotomous, inputs.
The deployment of the Simplex method, combined with dummy variables, was
therefore entirely successful in identifying and characterizing global optima in
all three case studies. The Simplex-based method was further shown to be of
equivalent efficiency to a DoE-based approach, represented here by D-Optimal
designs. Such an approach failed, however, to both capture trends and identify
optima, and led to poor operating conditions. It is suggested that the Simplex
variant is suited to development activities involving numerical and categorical
inputs in early bioprocess development.
PMID- 28497574
TI - Protein destabilization and loss of protein-protein interaction are fundamental
mechanisms in cblA-type methylmalonic aciduria.
AB - Mutations in the human MMAA gene cause the metabolic disorder cblA-type
methylmalonic aciduria (MMA), although knowledge of the mechanism of dysfunction
remains lacking. MMAA regulates the incorporation of the cofactor
adenosylcobalamin (AdoCbl), generated from the MMAB adenosyltransferase, into the
destination enzyme methylmalonyl-CoA mutase (MUT). This function of MMAA depends
on its GTPase activity, which is stimulated by an interaction with MUT. Here, we
present 67 new patients with cblA-type MMA, identifying 19 novel mutations. We
biochemically investigated how missense mutations in MMAA in 22 patients lead to
disease. About a third confer instability to the recombinant protein in bacterial
and human expression systems. All 15 purified mutant proteins demonstrated wild
type like intrinsic GTPase activity and only one (p.Asp292Val), where the
mutation is in the GTP binding domain, revealed decreased GTP binding. However,
all mutations strongly decreased functional association with MUT by reducing
GTPase activity stimulation upon incubation with MUT, while nine mutant proteins
additionally lost the ability to physically bind MUT. Finally, all mutations
interfered with gating the transfer of AdoCbl from MMAB to MUT. This work
suggests loss of functional interaction between MMAA and MUT as a disease-causing
mechanism that impacts processing and assembly of a cofactor to its destination
enzyme.
PMID- 28497575
TI - Recognition of Delirium in Postoperative Elderly Patients: A Multicenter Study.
AB - OBJECTIVES: To evaluate to what extent delirium experts agree on the diagnosis of
delirium when independently assessing exactly the same information and to
evaluate the sensitivity of delirium screening tools in routine daily practice of
clinical nurses. DESIGN: Prospective observational longitudinal study. SETTING:
Three medical centers in the Netherlands. PARTICIPANTS: Elderly postoperative
adults (n = 167). MEASUREMENTS: A researcher examined participants daily
(Postoperative Day 1-3) for delirium using a standardized cognitive assessment
and interview including the Delirium Rating Scale Revised-98 as global impression
without any cut-off values that was recorded on video. Two delirium experts
independently evaluated the videos and clinical information from the last 24
hours in the participants' record and classified each assessment as delirious,
possibly delirious, or not delirious. Interrater agreement between the delirium
experts was determined using weighted Cohen's kappa. When there was no consensus,
a third expert was consulted. Final classification was based on median score and
compared with the results of the Confusion Assessment Method for Intensive Care
Unit and Delirium Observation Scale that clinical nurses administered. RESULTS:
Four hundred twenty-four postoperative assessments of 167 participants were
included. The overall kappa was 0.61 (95% confidence interval = 0.53-0.68). There
was no agreement between the experts for 89 (21.0%) assessments and a third
delirium expert was needed for the final classification. Delirium screening that
nurses performed detected 32% of the assessments that the experts diagnosed as
(possibly) delirious. CONCLUSION: There was considerable disagreement in
classification of delirium by experts who independently assessed exactly the same
information, showing the difficulty of delirium diagnosis. Furthermore, the
sensitivity of daily delirium screening by clinical nurses was poor. Future
research should focus on development of objective instruments to diagnose
delirium.
PMID- 28497577
TI - Least speciose among the most speciose: Natural history correlates of
monospecific and bispecific genera of Rodentia and Soricomorpha.
AB - Monospecific and bispecific genera are of special concern as they represent
unique phylogenetic/evolutionary trajectories within larger clades. In addition,
as phylogenetically older taxa are supposed to be exposed to higher rarity and
extinction risk, monospecific and bispecific genera may be intrinsically more
prone to extinction risks than multispecies genera, although extinction risks
also depend on the ecological and biological strategy of the species. Here, the
distribution across biogeographical zones and the levels of threat to 2 speciose
orders of mammals (monospecific and bispecific genera of Rodentia and
Soricomorpha) are investigated in order to highlight major patterns at the
worldwide scale. In Rodentia, 39.7% of the genera (n = 490) were monospecific and
17.9% were bispecific. In Soricomorpha, 44.4% of the total genera (n = 45) were
monospecific and 15% were bispecific. There was a positive correlation between
the number of monospecific genera and the total number of genera per family.
Peaks of monospecific and bispecific genera richness were observed in
Neotropical, Oriental and Afrotropical regions in rodents and in the Palearctic
region in soricomorphs. Range size was significantly uneven across biogeographic
region in rodents (with larger ranges in Nearctic and Oriental regions and
smaller ranges in the Australian region), but there was no difference across
biogeographic regions in terms of range size in soricomorphs. Most of the
monospecific and bispecific genera occurred in forest habitat in both taxa. The
frequency distribution of the monospecific and bispecific genera across IUCN
categories did not differ significantly from the expected pattern using the total
rodent genera and the multispecies genera.
PMID- 28497576
TI - The space where aging acts: focus on the GABAergic synapse.
AB - As it was established that aging is not associated with massive neuronal loss, as
was believed in the mid-20th Century, scientific interest has addressed the
influence of aging on particular neuronal subpopulations and their synaptic
contacts, which constitute the substrate for neural plasticity. Inhibitory
neurons represent the most complex and diverse group of neurons, showing distinct
molecular and physiological characteristics and possessing a compelling ability
to control the physiology of neural circuits. This review focuses on the aging of
GABAergic neurons and synapses. Understanding how aging affects synapses of
particular neuronal subpopulations may help explain the heterogeneity of aging
related effects. We reviewed the literature concerning the effects of aging on
the numbers of GABAergic neurons and synapses as well as aging-related
alterations in their presynaptic and postsynaptic components. Finally, we
discussed the influence of those changes on the plasticity of the GABAergic
system, highlighting our results concerning aging in mouse somatosensory cortex
and linking them to plasticity impairments and brain disorders. We posit that
aging-induced impairments of the GABAergic system lead to an
inhibitory/excitatory imbalance, thereby decreasing neuron's ability to respond
with plastic changes to environmental and cellular challenges, leaving the brain
more vulnerable to cognitive decline and damage by synaptopathic diseases.
PMID- 28497578
TI - Effector and regulatory dendritic cells display distinct patterns of miRNA
expression.
AB - INTRODUCTION: MicroRNAs (miRNAs) contribute to the regulation of dendritic cell
(DC) polarization, thereby influencing the balance of adaptive immune responses.
Herein, we studied the expression of miRNAs in polarized DCs and analyzed whether
expression of these miRNAs could be associated with allergic rhinitis and
allergen immunotherapy (AIT) outcome. METHOD: Using specific culture conditions,
we differentiated immature human monocyte-derived DCs into DC1, DC2, and DCreg
subsets (supporting the differentiation of TH 1, TH 2 or regulatory T cells,
respectively). Profiling of miRNA expression was performed in these DC
subpopulations using microarrays. Levels of miRNAs specific for polarized DCs
were then evaluated in a cohort of 58 patients with allergic rhinitis and 25 non
allergic controls, as well as in samples from 30 subjects treated with sublingual
grass pollen tablets or placebo for four months. RESULTS: We successfully
identified 16 miRNAs differentially regulated between immature DCs, DC1, DC2, and
DCreg cells. In allergic rhinoconjunctivitis patients, the expression of two of
those miRNAs (miR-132 and miR-155), was down-regulated compared to non-allergic
individuals. However, the levels of these miRNAs were not significantly modified
following four months of grass pollen immunotherapy. CONCLUSIONS: Studying
polarized DCs and clinical samples from subjects with or without allergic
rhinoconjunctivitis, we demonstrated that the expression of two miRNAs linked to
effector DCs (i.e., DC1 and/or DC2 cells), was reduced in the blood of patients
with allergic rhinoconjunctivitis. Nevertheless, these miRNAs did not represent
relevant biomarkers to predict or follow-up AIT efficacy.
PMID- 28497580
TI - The evaluation of the relevance of thrombin generation and procoagulant activity
in thrombotic risk assessment in BCR-ABL-negative myeloproliferative neoplasm
patients.
AB - INTRODUCTION: It has been recently suggested that microparticles (MP) play a role
in the pathogenesis of thrombotic complications. This study aimed to assess the
contribution of procoagulant activity expressed by circulating MP in thrombotic
events in MPN patients. METHODS: Seventy-four MPN patients were enrolled in a
trans-sectional study. The MP procoagulant activity was measured using two
assays: (i) the thrombin generation (TG) assay used in different conditions with
the addition of both tissue factor (TF) and phospholipids (PL) and with the
addition of TF or PL alone and (ii) the PROCOAG-PPL assay. RESULTS: The mean age
was 62 (26 men and 48 women). The prevalence of thrombotic events was 28%. When
comparing patients with thrombosis to those without, age, sex, MPN type,
cardiovascular risk factors, and history of thrombosis were not significantly
associated with thrombosis. The JAK2 V617F mutation was significantly associated
with thrombotic events (90% vs 67%; P=.04). Results from the TG assay and the
PROCOAG-PPL assays did not demonstrate a significant association between the MP
procoagulant activity and thrombotic events. CONCLUSION: The MP procoagulant
activity did not predict thrombosis in MPN patients. The contribution of TG assay
in the assessment of the thrombotic risk is still in debate.
PMID- 28497581
TI - What could cognitive capital mean for China's children?
AB - Cognitive capital is an emerging paradigm that captures the criticality of
investing in children whilst neural proliferation and development of brain
architecture are at their peak. Distinct from financial capital, cognitive
capital represents investment in future human potential from interventions in
nutrition, health, education, child protection, and social welfare systems that
optimize brain development. The return on investment is significant given the
plasticity of the developing brain in response to positive stimuli. Investment in
brain development results in improved health and well-being, educational
outcomes, skills, employment, and quality of life. The inverse is also true.
Negative stimuli lead to depreciating cognitive capital, poorer mental and
physical health and educational outcomes, and decreased life chances. Cognitive
capital could be an organizing framework for China's next phase of development to
ensure the building of a prosperous society. Through significant commitment from
the government, China has seen remarkable improvements in under-five mortality,
literacy rates, access to basic education, life expectancy, and gross domestic
product in the past few decades as the result of an expansion of publicly funded
social services. Yet, inequities remain within and across communities and
regions. In 2015, China had a country ranking of 97 for gross national income per
capita, highlighting remaining challenges across the whole population. Cognitive
capital relies on a package of forward-looking policies that lead to equitable,
efficient, and effective use of existing and future resources. This is consistent
with the United Nations Convention on the Rights of the Child. Investments in
interventions that maximize optimal brain development in children, realize
children's rights, and contribute to future economic growth, defined as
"cognitive capital," represent a significant opportunity for improving children's
lives, nation-building, and future economic growth in China.
PMID- 28497579
TI - Modulation of basal cell fate during productive and transforming HPV-16 infection
is mediated by progressive E6-driven depletion of Notch.
AB - In stratified epithelia such as the epidermis, homeostasis is maintained by the
proliferation of cells in the lower epithelial layers and the concomitant loss of
differentiated cells from the epithelial surface. These differentiating
keratinocytes progressively stratify and form a self-regenerating multi-layered
barrier that protects the underlying dermis. In such tissue, the continual loss
and replacement of differentiated cells also limits the accumulation of oncogenic
mutations within the tissue. Inactivating mutations in key driver genes, such as
TP53 and NOTCH1, reduce the proportion of differentiating cells allowing for the
long-term persistence of expanding mutant clones in the tissue. Here we show that
through the expression of E6, HPV-16 prevents the early fate commitment of human
keratinocytes towards differentiation and confers a strong growth advantage to
human keratinocytes. When E6 is expressed either alone or with E7, it promotes
keratinocyte proliferation at high cell densities, through the combined
inactivation of p53 and Notch1. In organotypic raft culture, the activity of E6
is restricted to the basal layer of the epithelium and is enhanced during the
progression from productive to abortive or transforming HPV-16 infection.
Consistent with this, the expression of p53 and cleaved Notch1 becomes
progressively more disrupted, and is associated with increased basal cell density
and reduced commitment to differentiation. The expression of cleaved Notch1 is
similarly disrupted also in HPV-16-positive cervical lesions, depending on
neoplastic grade. When taken together, these data depict an important role of
high-risk E6 in promoting the persistence of infected keratinocytes in the basal
and parabasal layers through the inactivation of gene products that are commonly
mutated in non-HPV-associated neoplastic squamous epithelia. (c) 2017 The
Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of
Pathological Society of Great Britain and Ireland.
PMID- 28497582
TI - An objective definition for clinical suspicion of T-cell-mediated rejection after
liver transplantation.
AB - A uniform definition of clinical suspicion of T-cell-mediated rejection (TCMR) in
liver transplantation (LT) is needed to homogenize clinical decisions, especially
within randomized trials. This multicenter study included a total of 470 primary
LT recipients. The derivation cohort consisted of 142 patients who had clinically
driven liver biopsies at any time after LT. The external validation cohort
included 328 patients who underwent protocol biopsies at day 7-10 after LT. The
rates of moderate-severe histological TCMR were 33.8% in the derivation cohort
and 43.6% in the validation cohort. Independent predictors (ie, risk factors) of
moderate-severe TCMR in the derivation cohort were as follows: serum bilirubin >4
mg/dL (OR=5.83; P<.001), rising bilirubin within the 4 days prior to liver biopsy
(OR=4.57; P=.003), and blood eosinophils count >0.1*109 /L (OR=3.81; P=.004). In
the validation cohort, the number of risk factors was an independent predictor of
moderate-severe TCMR (OR=1.74; P=.001), after controlling for hepatitis C status.
The number of risk factors paralleled the rates of moderate-severe TCMR in the
derivation and validation cohorts (P<.001 in both comparisons). In conclusion,
increased serum bilirubin, rising bilirubin and eosinophilia are validated risk
factors for moderate-severe histological TCMR and could be used as objective
criteria to select candidates for liver biopsy.
PMID- 28497583
TI - Evaluation of athletes with complex congenital heart disease.
AB - As a result of improvements in congenital heart surgery, there are more adults
alive today with congenital heart disease (CHD) than children. Individuals with
cardiac birth defects may be able to participate in physical activities but
require proper cardiovascular evaluation. The American Heart Association and
American College of Cardiology released guidelines in 2015 for athletes with
cardiovascular abnormalities. The guidelines express that although restriction
from competitive athletics may be indicated for some, the majority of individuals
with CHD can and should engage in some form of physical activity. This case study
demonstrates the importance of combining all aspects of history, physical
examination, ECG, and imaging modalities to evaluate cardiac anatomy and function
in young athletes with complex CHD.
PMID- 28497584
TI - Recommended practice for laboratory reporting of non-invasive prenatal testing of
trisomies 13, 18 and 21: a consensus opinion.
AB - OBJECTIVE: Non-invasive prenatal testing (NIPT) for trisomies 13, 18 and 21 is
used worldwide. Laboratory reports should provide clear, concise results with
test limitations indicated, yet no national or local guidelines are currently
available. Here, we aim to present minimum best practice guidelines. METHODS: All
laboratories registered in the three European quality assurance schemes for
molecular and cytogenetics were invited to complete an online survey focused on
services provided for NIPT and non-invasive prenatal diagnosis. Laboratories
delivering NIPT for aneuploidy were asked to submit two example reports; one high
and one low risk result. Reports were reviewed for content and discussed at a
meeting of laboratory providers and clinicians held at the ISPD 2016 conference
in Berlin. RESULTS: Of the 122 laboratories that responded, 50 issued reports for
NIPT and 43 of these submitted sample reports. Responses and reports were
discussed by 72 attendees at the meeting. Consensus opinion was determined in
several areas and used to develop best practice guidelines for reporting of NIPT
results. CONCLUSIONS: Across Europe, there is considerable variation in reporting
NIPT results. Here, we describe minimum best practice guidelines, which will be
distributed to European laboratories, and reports audited in subsequent external
quality assurance cycles. (c) 2017 The Authors. Prenatal Diagnosis published by
John Wiley & Sons, Ltd.
PMID- 28497585
TI - Disseminated CD8-positive, CD30-positive cutaneous lymphoproliferative eruption
with overlapping features of mycosis fungoides and primary cutaneous anaplastic
large cell lymphoma following remote solitary lesional presentation.
AB - CD8-positive, CD30-positive cutaneous lymphoproliferative disorders constitute a
rare subset of T-cell lymphoproliferative conditions, including variants of
primary cutaneous anaplastic large cell lymphoma (ALCL), mycosis fungoides,
lymphomatoid papulosis type D, cutaneous gamma-delta T-cell lymphoma and
cutaneous peripheral T-cell lymphoma. These entities share overlapping clinical,
histopathologic and immunophenotypic features, presenting both a clinical and
pathological diagnostic challenge. Presented here is a 73-year-old man with a
disseminated, indolent CD30+, CD8+ cutaneous lymphoproliferative disorder with
overlapping clinical and histopathological features of both mycosis fungoides and
primary cutaneous ALCL, as well as features of lymphomatoid papulosis. To our
knowledge, this is the first case of a generalized CD8+, CD30+ eruption with
features of both mycosis fungoides and primary cutaneous ALCL arising following
an episode of solitary primary cutaneous CD8-positive ALCL.
PMID- 28497586
TI - R-Ras deficiency does not affect papain-induced IgE production in mice.
AB - INTRODUCTION: R-Ras GTPase has recently been implicated in the regulation of
immune functions, particularly in dendritic cell (DC) maturation, immune synapse
formation, and subsequent T cell responses. METHODS: Here, we investigated the
role of R-Ras in allergen-induced immune response (type 2 immune response) in
Rras deficient (R-Ras KO) and wild type (WT) mice. RESULTS: Initially, we found
that the number of conventional DC's in the lymph nodes (LNs) was reduced in R
Ras KO mice. The expression of co-stimulatory CD80 and CD86 molecules on these
cells was also reduced on DC's from the R-Ras KO mice. However, there was no
difference in papain-induced immune response between the R-Ras WT and KO as
measured by serum IgE levels after the immunization. Interestingly, neither the
DC number nor co-stimulatory molecule expression was different between WT and R
Ras KO animals after the immunization. CONCLUSIONS: Taken together, despite
having reduced number of conventional DC's in the R-Ras KO mice and low
expression of CD80 on DC's, the R-Ras KO mice are capable of mounting papain
induced IgE responses comparable to that of the WT mice. To our knowledge, this
is the first report addressing potential differences in in vivo allergen
responses regulated by the R-Ras GTPase.
PMID- 28497587
TI - Office-based procedures for diagnosis and treatment of esophageal pathology.
AB - BACKGROUND: Diagnostic and therapeutic office-based procedures under topical
anesthesia are emerging in the daily practice of laryngologists and head and neck
surgeons. Since the introduction of the transnasal esophagoscope, office-based
procedures for the esophagus are increasingly performed. METHODS: We conducted a
systematic review of literature on office-based procedures under topical
anesthesia for the esophagus. RESULTS: Transnasal esophagoscopy is an extensively
investigated office-based procedure. This procedure shows better patient
tolerability and equivalent accuracy compared to conventional transoral
esophagoscopy, as well as time and cost savings. Secondary tracheoesophageal
puncture, esophageal dilatation, esophageal sphincter injection, and foreign body
removal are less investigated, but show promising results. DISCUSSION: With the
introduction of the transnasal esophagoscope, an increasing number of diagnostic
and therapeutic office-based procedures for the esophagus are possible, with
multiple advantages. Further investigation must prove the clinical feasibility
and effectiveness of the therapeutic office-based procedures.
PMID- 28497588
TI - Facilitating early diagnosis of lung cancer amongst primary care patients: The
views of GPs.
AB - Early diagnosis of lung cancer (LC) is a policy priority. However, symptoms are
vague, associated with other morbidities, and frequently unrecognised by both
patients and general practitioners (GPs). This qualitative study, part of a
larger mixed methods study, explored GP views regarding the potential for early
diagnosis of LC within primary care. Five focus group discussions (FGDs) were
conducted with GPs (n = 16) at primary care practices (n = 5) across four
counties in south England. FGDs were audio-recorded, transcribed verbatim and
analysed using a framework approach. Four broad themes emerged: patients'
reporting of symptoms; GP response to symptoms; investigating LC, and; potential
initiatives for early diagnosis. GPs reported they often required high levels of
suspicion to refer patients on to specialist respiratory consultations, and
concerns of 'system overload' were prevalent. Greater access to more sensitive
diagnostic investigations such as computed tomography, was argued for by some,
particularly for symptomatic patients with negative chest X-rays. GPs challenged
current approaches to promoting earlier diagnosis through national symptom
awareness campaigns, arguing instead that interventions targeted at high-risk
individuals might be more effective without burdening services already under
pressure. Further work is needed to identify primary care patients who might most
benefit from such targeted interventions.
PMID- 28497589
TI - Asia-Pacific Colorectal Screening score: A useful tool to stratify risk for
colorectal advanced neoplasms in Vietnamese patients with irritable bowel
syndrome.
AB - BACKGROUND AND AIM: The Asia-Pacific Colorectal Screening (APCS) score has been
validated in several populations but not yet in patients with irritable bowel
syndrome (IBS). The aim of this study was to assess the performance of APCS score
in stratifying risk of colorectal advanced neoplasms (CAN) in Vietnamese IBS
patients. METHODS: Consecutive patients who fulfilled IBS diagnosis criteria
according to the Rome III were prospectively enrolled and underwent colonoscopy.
APCS score for each patient was calculated by summing the points attributed by
risk factors. Three tiers of risk were defined: 0-1 "average risk" (AR); 2-3
"moderate risk" (MR); and 4-7 "high risk" (HR). Logistic regression analysis was
performed to assess the relative risk of CAN in HR group and MR group compared
with AR group. RESULTS: There were 404 patients with excellent bowel preparation
and complete colonoscopy. The mean age was 48.8 +/- 11.2 years and male : female
ratio was 1.2:1. Twenty-eight patients (6.9%) were diagnosed with CAN: 19 (4.7%)
advanced adenoma and 9 (2.2%) invasive colorectal cancer. Patients in the MR and
HR tiers had 5.6-fold (95% confidence interval 1.2 to 24.7, P = 0.012) and 12.1
fold (95% confidence interval 2.6 to 56.2, P < 0.001) increased rates of CAN
compared with those in the AR tier, respectively. Three out of 9 patients with
invasive colorectal cancer had no alarm features but had high sum APCS score (2
in MR tier and 1 in HR tier). CONCLUSION: The APCS score is useful to identify
IBS patients with high risk of CAN for colonoscopy priority.
PMID- 28497590
TI - Multimodality characterization of a noncommunicating congenital duodenal
duplication cyst causing pyloric outflow obstruction in a young dog.
AB - A 10-month-old German Shepherd Dog presented for evaluation of intermittent
vomiting. Abdominal radiographs revealed a marked right cranial mass effect.
Initial differentials included abscess/cyst or less likely neoplasia from
undetermined origin. On abdominal ultrasound the mass appeared cystic and thin
walled. Computed tomography revealed a large cystic lesion originating from the
pyloroduodenal junction causing pyloric outflow obstruction. A noncommunicating
duodenal duplication cyst was found on exploratory laparotomy and further
confirmed with histopathology and immunohistochemistry. Enteric duplication cyst
should be considered as a differential in young dogs with gastrointestinal signs
and a cystic abdominal mass detected with different imaging modalities.
PMID- 28497591
TI - Hypophosphatemia after nontraumatic intracranial hemorrhage.
AB - BACKGROUND: The aim of this study was to assess the incidence and contributing
factors of hypophosphatemia and the association with poor long-term outcome after
nontraumatic intracranial hemorrhage. METHODS: This was a prospective,
observational study of patients with nontraumatic intracranial hemorrhage (i.e.,
aneurysmal or perimesencephalic subarachnoid hemorrhage, or spontaneous
intracerebral or intraventricular hemorrhage) treated in the intensive care unit
(ICU) at our university hospital. Plasma phosphate concentrations were measured
serially in 2-day sections during the 6 day study period. The ICU mortality was
recorded, 3-month and 1-year outcomes were assessed using the Glasgow Outcome
Scale. RESULTS: One hundred patients were enrolled. The frequency of
hypophosphatemia (Pi <= 0.65 mmol/l) was 70%. Chronic hypertension, acute
hydrocephalus, and diffuse brain edema were more common in patients with
hypophosphatemia compared with normophosphatemics (44% vs. 21%, P = 0.021; 59%
vs. 33%, P = 0.021; and 43% vs. 13%, P = 0.004, respectively). Hypophosphatemic
patients had higher maximum SOFA scores [10 (7-11) vs. 7.5 (5.75-10), P = 0.024].
Initial phosphate concentration correlated inversely with APACHE II score on
admission (rho = -0.304, P = 0.002) and SOFA score on the first ICU day (rho =
0.269, P = 0.008). There was no difference in outcome between hypophosphatemic
and normophosphatemic patients. In all five patients with severe hypophosphatemia
(Pi < 0.32 mmol/l) the functional outcome was good. CONCLUSION: Hypophosphatemia
was common in this patient population. The outcome was similar between
hypophosphatemic and normophosphatemic patients. Chronic hypertension, acute
hydrocephalus, diffuse brain edema and higher SOFA scores were more common in
patients with hypophosphatemia.
PMID- 28497592
TI - Hypoglycaemia seriousness and weight gain as determinants of cardiovascular
disease outcomes among sulfonylurea users.
AB - AIMS: Certain treatments for type 2 diabetes mellitus cause hypoglycaemia and
weight gain, and thus might counteract the benefits of intensive glucose control.
We quantify the association of cardiovascular disease (CVD) outcomes with
hypoglycaemia and weight gain among patients with type 2 diabetes treated with
sulfonylureas. MATERIALS AND METHODS: This cohort study included patients from
January 2009 through December 2014 who were selected from within a deidentified
nationwide electronic health records repository, including multiple provider
networks and electronic medical records systems. Hypoglycaemia measures from
structured data fields and free text clinical notes were categorized as serious
or non-serious. Covariate adjusted Poisson regression analysis was used to assess
the association between frequency of hypoglycaemia (by severity), or magnitude of
weight change, and incidence of acute myocardial infarction (AMI), congestive
heart failure (CHF) and stroke. RESULTS: Among 143 635 eligible patients, we
observed 5669 cases of AMI, 14 109 incident cases of CHF and 7017 cases of
stroke. Overall incidence rates were 1.53, 4.26 and 1.92 per 100 person-years for
AMI, CHF and stroke, respectively. The associations between overall hypoglycaemia
and each of the CVD outcomes were positive, with stronger associations observed
for serious hypoglycaemia and attenuated or null associations observed for non
serious hypoglycaemia. Weight change exhibited a U-shaped association with
increased risks associated with both weight loss and weight gain relative to
stable weight. CONCLUSIONS: This study provides evidence of increased CVD risk
associated with hypoglycaemia, especially with serious hypoglycaemia events.
While associations were attenuated with non-serious hypoglycaemia, the results
were suggestive of a potential increased risk.
PMID- 28497595
TI - Criteria for conceptualizing behavioural addiction should be informed by the
underlying behavioural mechanism.
PMID- 28497594
TI - The impact of regulatory action on the co-prescribing of renin-angiotensin system
blockers in UK primary care.
AB - PURPOSE: The aim of this study was to assess the impact of regulatory action
taken in June 2014 on the co-prescribing of renin-angiotensin system (RAS)
blockers in UK primary care. METHODS: RAS blocker prescriptions, issued between
01/01/2009-30/06/2015, were extracted from the Clinical Practice Research
Datalink to estimate the quarterly prevalence (number of patients with at least
one co-prescription) and incidence (number of patients first receiving a RAS
blocker co-prescription) of co-prescribing. Two different RAS blockers prescribed
on the same day constituted a co-prescription. RESULTS: A total of 880 364
patients were prescribed a single RAS blocker during the study period. Prevalence
of co-prescribing increased from 4812 patients per million person-years in Q1
2009 to 4865 in Q1 2010. A reduction then occurred decreasing to 2901 patients
per million person-years in Q2 2014 when the EU review concluded and continued to
decrease thereafter despite a continued increase in the prevalence of prescribing
of a single RAS blocker. Incidence of new co-prescribing decreased from 454
patients per million person-years in Q1 2009 to 159 in Q2 2014, but remained
relatively constant at ~119 patients per million person-years on average after
the EU review concluded. A total of 96% of co-prescriptions were for an ACE
inhibitor + ARB, and 4% accounted for an ACE inhibitor or ARB + renin inhibitor.
CONCLUSIONS: Recently, there has been a decrease in the prevalence and incidence
of RAS blocker co-prescribing. Reassuringly, overall co-prescribing reduced in
line with recommendations, although there was a decreasing trend prior to this
likely due in part to prior publication of the data used in the EU review. (c)
2017 Crown copyright. Pharmacoepidemiology and Drug Safety (c) 2017 John Wiley &
Sons, Ltd.
PMID- 28497593
TI - Polymorphism of receptor-type tyrosine-protein phosphatase delta gene in the
development of non-alcoholic fatty liver disease.
AB - BACKGROUND AND AIM: Some single-nucleotide polymorphisms (SNPs) are associated
with the development of non-alcoholic fatty liver disease (NAFLD). As one of the
genetic factors, PNPLA3 rs738409 (I148M) is important to associate with
pathogenesis of NAFLD. Because other SNPs remain unclear in Japan, we performed a
high-throughput sequencing that targeted more than 1000 genes to identify a novel
genetic variant in Japanese patients with NAFLD. METHODS: The present study in 36
NAFLD patients and 27 healthy volunteers was performed. A high-throughput
sequencer was used to detect the gene variations. Candidate genes were validated
by TaqMan SNP genotyping assay in 53 NAFLD patients and 41 healthy volunteers. To
investigate the function of candidate gene, we performed biochemical analyses in
cultured hepatocytes and liver tissues. RESULTS: EXO1 rs1047840, PTPRD
rs35929428, IFNAR2 rs2229207, CPOX rs1131857, IL23R rs1884444, IL10RA rs2228055,
and FAM3B rs111988437 were identified as candidate genetic variants, and PTPRD
rs35929428 was only extracted as a SNP predicting to cause protein dysfunction.
In validation analysis, PTPRD rs35929428 associated with the development of NAFLD
(P = 0.015, odds ratio = 5.00, 95% confidence interval: 1.33-18.70). In addition,
PTPRD rs35929428 was associated with Fib-4 index and with hepatic fat droplets.
Biochemical analyses indicated that PTPRD rs35929428 promoted dephosphorylation
of tyrosine 705 signal transducer and activator of transcription 3 (Tyr 705) in
hepatocytes. CONCLUSION: PTPRD rs35929428 was a novel SNP in patients with NAFLD.
Through exacerbation of the dephosphorylation of signal transducer and activator
of transcription 3 (Tyr 705) in hepatocytes, PTPRD rs35929428 might play a role
in hepatic lipid accumulation and fibrosis, followed by the development of NAFLD.
PMID- 28497596
TI - Development of immunochromatographic colloidal gold test strip for rapid
detection of Haemophilus influenzae in clinical specimens.
AB - AIMS: A simple and fast test strip for simultaneous detection of Haemophilus
influenzae, based on the theory of colloidal gold immunochromatography was
developed. METHODS AND RESULTS: In this study, monodispersional colloidal gold
and gold-labelled polyclonal antibody (AbP6Line) specific to the linear antigenic
determinant OMP6 of H. influenzae were prepared, and identified by UV-visible
spectroscopy (200-700 nm) and transmission electron microscopy. The test strip
was assembled on a plastic backing containing a sample pad, a conjugate pad, an
absorbent pad and a nitrocellulose membrane, on which test and control lines were
stuck. The strip showed us specific recognization of H. influenzae and did not
identify other common respiratory pathogens such as Streptococcus pneumoniae,
Mycoplasma pneumoniae, Moraxella catarrhalis and Legionella pneumophila. It was
shown that the detection limit of the test strip was as low as 1 * 106 CFU per ml
and the whole process can be completed within 10 min. The strips could be stored
at 4 degrees C for at least 6 months without losing sensitivity or specificity.
CONCLUSIONS: The test strip was specific, simple and convenient for rapid
detection of H. influenzae presenting good stability and reproducibility.
SIGNIFICANCE AND IMPACT OF THE STUDY: The test strip provides a simple,
convenient and specific tool for the on-site surveillance and diagnosis of H.
influenzae infection in clinical samples.
PMID- 28497597
TI - Constructing a theory of the triple typology: Some (second) thoughts on
nomothetic and idiographic approaches to personality.
AB - Our fundamental scientific task is to convert observations of particular persons
behaving in particular ways in particular situations into assertions that certain
kinds of persons will behave in certain kinds of ways in certain kinds of
situations, that is, to construct triple typologies or equivalence classes-of
persons, of behaviors, and of situations-and to fashion theories of personality
that relate these equivalence classes to one another. It is argued that the
different approaches to the study of personality are distinguished from one
another not by whether they are idiographic or nomothetic but by the strategies
they employ for constructing-or ignoring-each of these three types of equivalence
classes. The likely attributes of a successful interactional theory of
personality-one that would embrace the entire triple typology-are proposed and
discussed.
PMID- 28497598
TI - Aggregation and beyond: Some basic issues on the prediction of behavior.
AB - Failure to appreciate the role that aggregation plays in increasing reliability
and validity and in establishing the range of generalization of findings has
resulted in misunderstandings about the stability of behavior across time and
situations, and in the conduct of experiments that produce results that tend to
be neither generalizable nor replicable. Appropriate aggregation can reduce error
variance associated with the unrepresentativeness of individual stimuli,
situations, occasions, judges, items of behavior, and subjects. Inappropriate
aggregation can result not only in a loss of information but also in a reduction
in reliability as well as validity. Different approaches to prediction with
single items of behavior are discussed, and it is concluded that single items
tend to be too unreliable and too narrow in scope to measure broad dispositions
such as traits. A major emphasis is that behavior is often so highly
situationally specific that unless this is taken into account by procedures such
as aggregation over situations and/or occasions, or by the investigation of
events that are so highly ego-involving that experimental effects dominate
situation-ally unique effects, results will tend to be unreplicable or
ungeneralizable, no matter what their level of statistical significance.
PMID- 28497599
TI - Studies in intuitive personology from an idiothetic point of view: Implications
for personality theory.
AB - Following Lamiell's (1981) critique of the individual differences approach to the
scientific study of personality, questions have arisen concerning (a) the nature
of the empirical research to which the "idiotheric" framework he proposed as an
alternative has thus far led, and (b) the wider theoretical implications of that
research. The present article seeks to address these questions within the medium
of research on the nature of the reasoning process by which lay persons formulate
and express subjective personality impressions. It is argued that the findings of
this research offer strong empirical support for a conception of the intuitive
personologist as a dialectician. Among other things, the discussion of these
findings focuses on their implications for a humanistic conception of the
relation between cognition and behavior, and thus of personality more broadly
defined.
PMID- 28497600
TI - The "consistency" controversy and the accuracy of personality judgments.
AB - Areas of clear and acknowledged disagreement in the personality literature's
"consistency controversy" are surprisingly difficult to pin down. The present
essay suggests that one basic and real disagreement nowadays is the admissability
of subjective judgments of personality as data: Personologists are willing to use
them, and situationists are not. Situationists generally regard judgments as so
influenced by error as to be essentially unusable, and instead prefer direct
measurements of specific behaviors. The relative uses and limitations of global
judgments and specific measures are considered. It is concluded that any position
that judgments reflect "nothing but" error is untenable. It is further concluded
that each sort of data has distinct uses and limitations, provides a check on the
other, and is indispensable.
PMID- 28497601
TI - Self-knowledge: An expanded view.
AB - This paper argues for a more extensive study of self-knowledge. From the
cognitive perspective, self-knowedge is a critical component of personality.
Until quite recently, however, the study of self-knowledge has been narrowly
conceived, focusing primarily on how individuals describe their roles and
characteristic behaviors. Yet individuals also have knowledge about their
preferences and values, their goals and motives, and their rules and strategies
for regulating behavior. These dynamic aspects of self-knowledge are significant
because they can be importantly revealing of future behavior. The content and
organization of self-knowledge is important first because it indicates which
domains of behavior are regarded as the most self-relevant. It is in these
domains that the strongest links between personality and behavior will be
observed. Second, self-knowledge cognitively represents desired and undesired
states for the self, as well as specific ideas about how to realize or avoid
these states. It thus indicates the likely course of behavior in self-relevant
domains. A number of recent research efforts can be intepreted as explorations of
self-knowledge. These are briefly reviewed and integrated to provide a general
outline for an expanded view of self-knowledge.
PMID- 28497602
TI - Interactionism, idiographics, and the social psychological invasion of
personality.
AB - The present paper discusses three recent developments in the field of
Personality: (1) an infusion of social psychologists, (2) a proliferation of
interactionist models, (3) the development of methodological strategies combining
nomothetic and idiographic approaches. Advantages and disadvantages of these
developments are discussed, and three problems associated with them are
addressed: (1) an overemphasis on phenomenology, (2) an overemphasis on
idiosyncracy, and (3) an unsatisfactory level of theory development. It is
concluded that the present developments have had a stimulating effect on the
field but they need to be integrated with the traditional personological goals
of: (1) developing taxonomy of individuals (as well as a taxonomy of
interactions) and (2) developing a more satisfactory theory of the whole organism
within which to embed our minitheories. We recommend that such a theory attempt
to incorporate the insights of the social learning and social cognition
approaches with the recent and exciting developments in evolutionary theory.
PMID- 28497603
TI - Self-attention and self-report: The "veridicality" hypothesis.
AB - Wicker (1969) summarized the state of the art in the area of attitude/behavior
consistency by suggesting that attitude measures are often only slightly related
to overt behaviors. Since that time literally hundreds of studies have been
conducted dealing with the question of how the predictive validity of self
assessment can be improved-above the 30 figure that Wicker suggested represents
the typical upper limit of correlations between self-reported attitudes and
behavior. This article deals with perhaps one of the simplest factors that does
appear to be related to accurate self-assessment: internal focus of attention.
Research in the area of self-awareness theory is discussed, leading to the
conclusion that assessments of various aspects of the self, including attitudes,
cognitions, and affective and somatic states, usually are more accurate when they
are made by a respondent whose attention is self-directed. By the same token,
overt behavior also tends to be more consistent with previously expressed
attitudes when it occurs under conditions conducive to self-focus. In discussing
this research, it is suggested that self-awareness promotes accuracy in two ways:
(a) It focuses the respondent's attention more carefully on those aspects of the
self made relevant by the instrument and (b) it increases the person's motivation
to report accurately on those self-dimensions. It is also suggested, however,
that this latter factor can sometimes work against consistency. In this regard, a
variety of situations are discussed in which motives that may conflict with the
desire to report accurately, such as ego-protectiveness, are also enhanced by
self-focused attention. Finally, a number of empirical questions are presented as
guidelines for future research.
PMID- 28497604
TI - Personality and prediction: An introduction.
PMID- 28497605
TI - Parallals between attitudes and traits as predictors of behavior.
AB - Both attitudes and traits have served as within-person constructs intended to
permit the prediction of later behavior. Despite this similarity, research in the
two domains has tended to progress in a relatively independent fashion. A number
of parallels between the attitude and trait literature are noted with regard to
definitions of the constructs and their utility as predictors of behavior.
Parallels with respect to the identification of variables that moderate the
attitude-behavior and trait-behavior relation are also discussed, as are
similarities in the potential processes by which attitudes and traits guide
behavior. It is concluded that the parallels are so extensive that research in
each domain would benefit from an increased exchange of theory, methods, and
findings.
PMID- 28497606
TI - Idiographic goals and methods in the study of lives.
AB - The goal of psychology is "the development of generalizations of ever increasing
scope, so that greater and greater varieties of phenomena may be explained by
them, larger and larger numbers of questions answered by them, and broader and
broader reaching predictions and decisions based upon them." Leon Levy (1970, p.
5) "To generalize is to be an idiot." William Blake ABSTRACT: Learning what is
true of persons-in-general and of groups of people often has severe limitations
in enabling us to understand and predict the behavior of individuals. There are
many important problems in describing, explaining, making predictions about, and
intentionally changing the course of experience in individual lives that cannot
be adequately addressed without the use of idiographic methods. The purposes of
this paper are to contribute to a conceptual clarification of the idiographic
approach and its place within psychology, to review and respond to a number of
common criticisms of the idiographic approach, and finally, to update and extend
Allport's survey of available idiographic methods.
PMID- 28497607
TI - Alternatives in the pursuit of the predictability and consistency of persons:
Stable data that yield unstable interpretations.
AB - After a review of the historical roots of current issues in personality
psychology, useful sources for prediction are summarized and some current
convergences in the search for coherence are identified. The value of people as
expert assessors is reiterated and the stability, consistency, and predictability
of behavior are distinguished as multiple issues. In the pursuit of consistency
in social behavior, two major routes emerge. One route aggregates data across
situations and response modes, thereby reducing the variance from those sources,
and identifies the resulting stable individual differences. The second route
assesses consistency from situation to situation, searches for its psychological
bases, and focuses on the discriminativeness of behavior as well as its
coherence. Each route serves different purposes and has value for those different
goals; neither one preempts the other. Years of research on the consistency of
social behavior from situation to situation have yielded stable results that
sometimes are used to reach opposite interpretations. But these puzzling
differences reflect the two contrasting routes and goals in the search for
consistency, not instabilities in the data nor a neglect of psychometric
principles. Theory-guided predictions within particular empirical contexts are
needed now to explore more deeply when and how either discriminative or more
generalized patterns of coherence occur, and to illuminate their psychological
bases with increasing precision.
PMID- 28497608
TI - The influence of individuals on situations: Implications for understanding the
links between personality and social behavior.
AB - In an analysis of the nature and origins of predictability in social behavior,
two propositions are considered: (1) There exist categories of individuals whose
social behavior is readily predictable from measures of personal attributes such
as attitudes, traits, and dispositions as well as categories of individuals whose
social behavior is readily predictable from situational and interpersonal
specifications of behavioral appropriateness; (2) underlying these differences in
predictability are systematic choices to enter and to spend time in social
settings and interpersonal contexts that promote and facilitate one or other of
these characteristic behavioral orientations. The implications of these
propositions for the study of personality and social behavior are considered in
the specific case of the psychological construct of self-monitoring and in the
general case of understanding the reciprocal influences of individuals and their
social worlds.
PMID- 28497609
TI - Implicit psychophysiology: Effects of common beliefs and idiosyncratic
physiological responses symptom reporting.
AB - Every individual exhibits unique perceptual, behavioral, and physiological
responses within and across a variety of settings. Despite the idiosyncratic
nature of responses, we seek to establish theories that generalize across a large
number of individuals. A strict idiographic method intensively examines the
response patterns of a small number of individuals, whereas a nomothetic approach
focuses on common responses across a large number of individuals. In the present
investigation, we seek to learn how individuals perceive and report physical
symptoms and sensations. We offer a methodology that capitalizes on the unique
physiological responses of individuals but, at the same time, assumes that the
underlying perceptual processes relevant to symptom reporting are comparable
across individuals. Our approach, then, is both idiographic and nomothetic. As
will be discussed, this integrative approach has the potential to be applied to a
multitude of behaviors and processes that are of interest to social and
personality psychologists.
PMID- 28497610
TI - Epilepsia partialis continua after an anterior circulation ischaemic stroke.
AB - BACKGROUND AND PURPOSE: Although cerebrovascular disorders are the main cause of
epilepsia partialis continua (EPC) in adulthood, the frequency of EPC after
stroke is unknown. The aim was to prospectively ascertain its frequency 1 year
after an ischaemic stroke. METHODS: This was a prospective study of consecutive
acute anterior circulation ischaemic stroke patients, previously independent,
with an admission National Institutes of Health Stroke Scale score >=4, an acute
ischaemic lesion on imaging and no previous epileptic seizures. During admission
patients received standardized diagnostic and medical care and were submitted to
a neurophysiological evaluation protocol. One year after stroke, patients were re
evaluated by an epilepsy expert neurologist and performed a video
electroencephalogram with electromyography co-registration whenever myoclonus was
observed during neurological examination for jerk-locked back averaging analysis
(JLBA). EPC was defined as continuously repeated fragments of epileptic seizures,
with preserved consciousness, lasting at least 1 h, and representing locally
restricted epileptic activity. RESULTS: In all, 151 acute anterior circulation
stroke patients were consecutively included and prospectively evaluated, but 23
died in the first year. One year after stroke, from 127 patients alive, 117
(92.1%) underwent clinical and neurophysiological evaluation. In two (1.7%)
patients, EPC diagnosis was made both by clinical and electroencephalographic
criteria, namely JLBA. Both patients had a history of remote symptomatic seizures
and one of them acute symptomatic seizures and non-convulsive status epilepticus
criteria during the first 7 days after stroke. CONCLUSIONS: Despite its low
frequency, the high stroke incidence makes post-stroke EPC relevant. This study
draws attention to this recognizable condition with therapeutic and eventually
prognostic implications.
PMID- 28497611
TI - Co-inheritance of alpha0 -thalassemia elevates Hb A2 level in homozygous Hb E:
Diagnostic implications.
AB - INTRODUCTION: Differentiation of homozygous hemoglobin (Hb) E with and without
alpha0 -thalassemia is subtle on routine hematological ground. We examined in a
large cohort of homozygous Hb E if the level of Hb A2 is helpful. METHODS: A
total of 592 subjects with homozygous Hb E were recruited from ongoing
thalassemia screening program. Additionally, five couples at risk of having
fetuses with Hb Bart's hydrops fetalis who were homozygous Hb E were also
investigated. Hb analysis was performed using capillary electrophoresis system.
Globin genotypes were defined by DNA analysis. RESULTS: Subjects were classified
into four groups including pure homozygous Hb E (n=532), homozygous Hb E/alpha0
thalassemia (n=48), Hb Constant Spring EE Bart's disease (n=8), and Hb EE Bart's
disease (n=4). The levels of Hb A2 were found, respectively, to be 4.97+/-0.69,
6.64+/-1.02, 4.86+/-0.87, and 7.60+/-1.04%. Among five couples at risk, alpha0
thalassemia was identified in three subjects with Hb A2 >6.0%. CONCLUSIONS:
Increased Hb A2 level is a useful marker for differentiation of homozygous Hb E
with and without alpha0 -thalassemia. This should lead to a significant reduction
in number of referral cases of homozygous Hb E for molecular testing of alpha0
thalassemia in routine practice.
PMID- 28497612
TI - Accurate assessment of alpha-gal syndrome using cetuximab and bovine
thyroglobulin-specific IgE.
AB - SCOPE: IgE against galactose-alpha-1,3-galactose (alpha-Gal) causes alpha-gal
syndrome. Bovine thyroglobulin (BTG) and cetuximab share this epitope. We aimed
to determine the utility of specific IgE (sIgE) against cetuximab as compared to
BTG for diagnosing alpha-gal syndrome. METHODS AND RESULTS: Twelve patients with
alpha-gal syndrome, 11 patients with immediate beef or pork allergy, 18
asymptomatic individuals with meat sensitization, and 10 non-atopic subjects were
enrolled. We checked the levels of sIgE against BTG and cetuximab using the
streptavidin CAP assay. Additionally, IgE reactivity to BTG and cetuximab was
assessed by immunoblotting. All alpha-gal syndrome patients had a high
concentration of sIgE against BTG, and cetuximab. In contrast to alpha-gal
syndrome, patients with immediate allergic reactions to meat consumption and
those with asymptomatic sensitization had significantly lower concentration of
BTG and cetuximab sIgE, and a high prevalence of sIgE against bovine or porcine
serum albumin. Although the concentration of sIgE against alpha-gal was lower in
individuals with asymptomatic sensitization, IgE immunoblotting showed the
presence of sIgE against alpha-Gal in this group. CONCLUSION: Differentiation of
alpha-gal syndrome from patients with immediate allergy to meat consumption or
asymptomatic sensitization requires quantification of cetuximab- or BTG-induced
sIgE via detection of IgE for alpha-gal.
PMID- 28497613
TI - Effectiveness of a nurse-led preadmission intervention for parents of children
with profound multiple disabilities undergoing hip-joint surgery: A quasi
experimental pilot study.
AB - PURPOSE: The aim of this study was to assess the effectiveness of a family
centered care (FCC) intervention provided by an advanced practice nurse (APN) for
parents of children with profound disabilities undergoing surgery. DESIGN AND
METHODS: In a quasi-experimental design, we used the MPOC-20 to assess
satisfaction with FCC and interviews to identify potential mechanisms for
improving satisfaction. RESULTS: There was a positive effect on the MPOC-20
domain "general information," albeit with a small effect size (Cohen's d = 0.35).
The interviewed parents expected additional support. PRACTICE IMPLICATIONS:
Emphasis should be placed on providing comprehensive care coordination by an
experienced APN. Shared care management is crucial in improving FCC.
PMID- 28497615
TI - Quantification of rat supraglottic laryngeal sensation threshold.
AB - OBJECTIVE: Laryngeal adductor response (LAR) to air puff is used as a reliable
method in evaluating sensation thresholds (ST) in human laryngeal sensory
disorders. This method has been difficult to perform in small subjects such as
rodents. The aims of this study were to 1) evaluate ST to air puff under
binocular microlaryngoscopy in rats to evaluate laryngeal sensory disorders, 2)
determine sensory thresholds at varying target locations, and 3) determine the
ideal depth of anesthesia. STUDY DESIGN: Animal study. METHODS: Rats were induced
with ketamine/xylazine. The level of anesthesia was monitored by spontaneous
glottic closure and corneal reflex testing. Air puffs were delivered to the
epiglottis, arytenoid, and piriform sinus at varied pressures with pulse time
kept constant. Sensation thresholds were determined by direct visualization of
the larynx using a binocular microscope. Topical lidocaine was then applied to
the larynx and ST was determined. Trials were repeated in a small subset of
animals. RESULTS: Twenty-six trials were performed in 14 rats. Mean STs were 39
+/- 9.7 mm Hg at the epiglottis, 48.8 +/- 10.5 at the arytenoid, and not
detectable at the pyriform sinus. Repeated trials demonstrated consistent
results. Lidocaine effectively ablated the LAR in each trial. The LAR was
difficult to induce while corneal reflex was absent and was difficult to
distinguish from spontaneous glottic closures while under lighter sedation.
CONCLUSION: Air pulse stimulation in rats is a simple, reliable, and effective
way to determine laryngopharyngeal STs in rats and can be used as an efficient
and affordable method for experimentation involving laryngeal sensory disorders.
LEVEL OF EVIDENCE: NA. Laryngoscope, 127:E265-E269, 2017.
PMID- 28497614
TI - Broad Th2 neutralization and anti-inflammatory action of pentosan polysulfate
sodium in experimental allergic rhinitis.
AB - BACKGROUND: Th2 cytokines like interleukin-4, -5, and -13 are regarded as
important drivers of the immunopathology underlying allergic rhinitis (AR) and
asthma. The present study explores the capacity of pentosan polysulfate sodium
(PPS), a semi-synthetic heparin-like macromolecular carbohydrate, to bind Th2
cytokines and exert biological neutralization in vitro, as well as anti
inflammatory actions in vivo. METHODOLOGY: The capacity of PPS to bind
recombinant Th2 cytokines was tested with surface plasmon resonance (SPR)
technology and biological Th2 neutralization was assessed by Th2-dependent
proliferation assays. The in vivo anti-inflammatory action of PPS was studied
using a validated Guinea-pig model of AR. RESULTS: Binding studies revealed a
strong and specific binding of PPS to IL-4, IL-5, and IL-13 with IC values
suggesting as stronger cytokine binding than for heparin. Cytokine binding
translated to a biological neutralization as PPS dose dependently inhibited Th2
dependent cell proliferation. Topical administration of PPS 30 min prior to nasal
allergen challenge of sensitized animals significantly reduced late phase plasma
extravasation, luminal influx of eosinophils, neutrophils, and total lavage
leukocytes. Similar, albeit not statistically secured, effects were found for
tissue leukocytes and mucus hyper-secretion. The anti-inflammatory effects of PPS
compared favorably with established topical nasal steroid treatment. CONCLUSION:
This study points out PPS as a potent Th2 cytokine-binding molecule with
biological neutralization capacity and broad anti-inflammatory effects in vivo.
As such PPS fulfills the role as a potential candidate molecule for the treatment
of AR and further studies of clinical efficacy seems highly warranted.
PMID- 28497616
TI - CHARMM-GUI ligand reader and modeler for CHARMM force field generation of small
molecules.
AB - Reading ligand structures into any simulation program is often nontrivial and
time consuming, especially when the force field parameters and/or structure files
of the corresponding molecules are not available. To address this problem, we
have developed Ligand Reader & Modeler in CHARMM-GUI. Users can upload ligand
structure information in various forms (using PDB ID, ligand ID, SMILES,
MOL/MOL2/SDF file, or PDB/mmCIF file), and the uploaded structure is displayed on
a sketchpad for verification and further modification. Based on the displayed
structure, Ligand Reader & Modeler generates the ligand force field parameters
and necessary structure files by searching for the ligand in the CHARMM force
field library or using the CHARMM general force field (CGenFF). In addition,
users can define chemical substitution sites and draw substituents in each site
on the sketchpad to generate a set of combinatorial structure files and
corresponding force field parameters for throughput or alchemical free energy
simulations. Finally, the output from Ligand Reader & Modeler can be used in
other CHARMM-GUI modules to build a protein-ligand simulation system for all
supported simulation programs, such as CHARMM, NAMD, GROMACS, AMBER, GENESIS,
LAMMPS, Desmond, OpenMM, and CHARMM/OpenMM. Ligand Reader & Modeler is available
as a functional module of CHARMM-GUI at http://www.charmm-gui.org/input/ligandrm.
(c) 2017 Wiley Periodicals, Inc.
PMID- 28497617
TI - Association of NPR3 polymorphism with risk of essential hypertension in a Chinese
population.
AB - WHAT IS KNOWN AND OBJECTIVE: Essential hypertension (EH) is a common disease
exhibiting large individual difference in occurrence, development and treatment
response. Genetic factors are implicated in the development and progression of
EH. This study aimed to explore the association between NPR3 single nucleotide
polymorphism rs2270915 (A/G, Asn521Asp) and the risk of EH in a Chinese Han
population by a case-control study. METHODS: The study was a single-centre, case
control trial, in which a total of 287 EH patients and 289 age- and sex-matched
healthy controls were enrolled. The inclusion criteria were as follows: Han
Chinese origin, male or female patients, systolic blood pressure (SBP) >=140 mm
Hg and/or diastolic blood pressure (DBP) >=90 mm Hg. The healthy controls were
subjects without histories of cardiovascular or cerebrovascular diseases. NPR3
rs2270915 polymorphism was genotyped by polymerase chain reaction-restriction
fragment length polymorphism (PCR-RFLP). In addition, primary human umbilical
vein endothelial cells (HUVECs) were isolated from 19 fresh human umbilical cords
and cultured. Atrial natriuretic peptide (ANP) concentration in cell medium was
determined by enzyme-linked immunosorbent assay (ELISA). NPR3 mRNA expression was
determined by real-time semi-quantitative PCR. RESULTS AND DISCUSSION: No
significant difference in genotype distribution of NPR3 rs2270915 polymorphism
was observed between cases and controls (P>.05). Patients carrying the rs2270915
G allele showed decreased SBP, and the difference was marginal. As compared with
cells carrying the rs2270915 AA genotype, those with the AG genotype showed
significantly lower NPR3 mRNA expression levels (P<.05) and lower medium ANP
concentration (P<.001). WHAT IS NEW AND CONCLUSION: This study suggested that
NPR3 rs2270915 polymorphism was associated with decreased SBP level marginally in
EH patients in a Chinese Han population, and the polymorphism may function
through decreasing NPR3 mRNA expression and ANP level.
PMID- 28497618
TI - Crocodilian perivitelline membrane-bound sperm detection.
AB - Advanced reproductive technologies (ART's) are often employed with various taxa
to enhance captive breeding programs and maintain genetic diversity.
Perivitelline membrane-bound (PVM-bound) sperm detection has previously been
demonstrated in avian and chelonian species as a useful technique for breeding
management. In the absence of embryotic development within an egg, this technique
can detect the presence of sperm trapped on the oocyte membrane confirming
breeding, male reproductive status, and pair compatibility. PVM-bound sperm were
successfully detected in three clutches of Cuban crocodile (Crocodylus rhombifer)
eggs at the Smithsonian's National Zoological Park (NZP) for the first time in
any crocodilian species. PVM-bound sperm were detected in fresh and incubated C.
rhombifer eggs, as well as eggs that were developing (banded) and those that were
not (not banded). The results of this study showed significant differences in
average sperm densities per egg between clutches (p = 0.001). Additionally, there
was not a significant difference within clutches between eggs that banded and
those that did not band (Clutch A, p = 0.505; Clutch B, p = 0.665; Clutch C, p =
0.266). The results of this study demonstrate the necessity to microscopically
examine eggs that do not develop (do not band), to determine if sperm is present,
which can help animal managers problem solve reproductive shortcomings. PVM-bound
sperm detection could be a useful technique in assessing crocodilian breeding
programs, as well as have potential uses in studies assessing sperm storage,
artificial insemination, and artificial incubation.
PMID- 28497619
TI - Change in over-refraction after scleral lens settling on average corneas.
AB - PURPOSE: The purpose of this study was to determine the change in over
refraction, if any, after a scleral lens settled on the eye for 6-8 h. METHODS:
Sixteen patients of varying refractive errors and normal corneal curvatures
(measured with PentacamTM Oculus) were fitted with trial Mini-Scleral Design
(MSD) scleral lenses (15.8 mm diameter) in one eye. The sagittal depths of the
scleral lenses were selected by adding 350 MUm to the corneal sagittal heights
measured at a chord length of 15 mm with the VisanteTM optical coherence
tomographer (OCT) anterior segment scans and picking the closest available trial
lens in the set. Initial measurements were taken 30 min after lens insertion and
included an auto-refraction, subjective refraction, and best sphere refraction
over the contact lens. Visual acuities and VisanteTM OCT anterior segment scans
were also taken. These measurements were repeated after 6-8 h of lens wear.
RESULTS: Over the trial wearing period, the average change in the spherical
component of the over-refraction was +0.06 D (S.D. 0.17) (p = 0.16). The average
change in cylinder was +0.04 D (S.D. 0.19) (p = 0.33). The average absolute
change in axis was 1.06 degrees (S.D. 12.11) (p = 0.74). The average change in
best sphere was +0.13 +/- 0.30 D (p = 0.12). There was no significant change in
visual acuity with the best sphere over-refraction over the 6-8 h wearing period.
There was a significant change in central corneal clearance over the wearing
period of 83 MUm (S.D. 22) (p < 0.0001). CONCLUSION: Despite a significant change
in the central corneal clearance due to thinning of the fluid reservoir as the
scleral lens settled (an average decrease of 83 MUm after wearing the lenses for
6-8 h), there was not a statistically significant change in the subjective over
refraction (sphere, cylinder, and axis) or best sphere or visual acuity. This
study has confirmed that there is no link between reduction in central corneal
clearance and change in over-refraction for average corneas.
PMID- 28497620
TI - Accelerated whole-heart MR angiography using a variable-density poisson-disc
undersampling pattern and compressed sensing reconstruction.
AB - PURPOSE: To accelerate whole-heart three-dimension MR angiography (MRA) by using
a variable-density Poisson-disc undersampling pattern and a compressed sensing
(CS) reconstruction algorithm, and compare the results with sensitivity encoding
(SENSE). METHODS: For whole-heart MRA, a prospective variable-density Poisson
disc k-space undersampling pattern was developed in which 1-2% of central part of
k-space was fully sampled, and sampling in the remainder decreased exponentially
toward the periphery. The undersampled data were then estimated using CS
reconstruction. In patients, images using this sequence with an undersampling
rate of ~6 were compared with those using a SENSE rate of 2 (n = 15) and a SENSE
rate of 6 (n = 13). RESULTS: Compared with SENSE rate 2, CS rate 6 images had
similar objective border sharpness, significantly lower subjective image quality
scores at all four locations (all P < 0.01), and shorter scan times (P < 0.05).
Compared with SENSE rate 6, CS rate 6 had similar objective border sharpness at
all four locations, significantly better subjective image quality scores at three
of four locations (all P < 0.01), and similar scan times (P = 0.24). CONCLUSION:
Compared with SENSE with a comparable acceleration rate, a variable-density
Poisson-disc undersampling pattern and CS reconstruction achieved better
subjective image quality and similar border sharpness. Magn Reson Med 79:761-769,
2018. (c) 2017 International Society for Magnetic Resonance in Medicine.
PMID- 28497621
TI - Endomyocardial and pericardial aspergillosis in critically ill patients.
AB - Invasive aspergillosis(IA) is a potentially lethal complication of Aspergillus
infection affecting mainly immunocompromised hosts; however, during the last two
decades its incidence was increasingly observed in critically ill immunocompetent
patients. The objective of this study is to describe the clinical characteristics
of histologically proven endomyocardial and pericardial invasion, in the context
of IA, in critically ill patients. Eight critically ill patients with
histopathological confirmation of endomyocardial/pericardial aspergillosis were
evaluated. Risk factors, clinical and laboratory characteristics, treatment,
histopathological characteristics and mortality were recorded. Signs and symptoms
of cardiac dysfunction were not observed in any of the patients. Therapy was
administered to six of them shortly after the first positive culture. The
observed histopathological lesions included haemorrhagic lesions, small vessels
with central thrombosis and surrounding consolidated tissue with necrosis.
Voriconazole, caspofungin, lipid amphotericin B and itraconazole were the used
antifungals. The mortality rate was high (87.5%). Endomyocardial and pericardial
aspergillosis are devastating complications of invasive aspergillosis. Clinical
suspicion is low making the diagnosis difficult, therefore histopathological
examination of tissues are required. The mortality is high.
PMID- 28497622
TI - Non-contrast-enhanced T1 -weighted MRI of myocardial radiofrequency ablation
lesions.
AB - PURPOSE: To demonstrate imaging of radiofrequency ablation lesions with non
contrast-enhanced T1 -weighted (T1w) MRI. METHODS: Fifteen swine underwent left
ventricular ablation followed by MRI using different preparations: endocardial or
epicardial ablation of naive animal, or endocardial ablation of animal with
myocardial infarction. Lesion imaging was performed using free-breathing, non
contrast-enhanced, T1w sequence with long inversion time (TI). Also acquired were
T1 maps and delayed contrast-enhanced (DCE) imaging. Hearts were excised for ex
vivo imaging, and sliced for gross pathology and histology. RESULTS: All
ablations were visibly enhanced in non-contrast-enhanced T1w imaging using TI =
700 ms. T1w enhancement agreed with regions of necrosis in gross pathology and
histology. Enhanced lesion cores were surrounded by dark bands containing
contraction band necrosis, hematoma, and edema. In animals with myocardial
infarction, chronic scar was hypointense in T1w, whereas acute ablations were
enhanced, allowing discrimination between chronic scar and acute lesions, unlike
DCE. Contrast was sufficient to create 3D volume renderings of lesions after
minor postprocessing. CONCLUSIONS: Non-contrast-enhanced T1w imaging with long TI
promises to be an effective method for visualizing necrosis within radiofrequency
ablation lesions. Enhancement is more specific and stationary than that from DCE.
The imaging can be repeated as needed, unlike DCE, and may be especially useful
for assessing ablations during or after a procedure. Magn Reson Med 79:879-889,
2018. (c) 2017 International Society for Magnetic Resonance in Medicine.
PMID- 28497623
TI - Gangrene caused by topically applied home-prepared aconite liniment.
PMID- 28497624
TI - Two new cases of severe allergic contact dermatitis caused by acetophenone azine.
PMID- 28497625
TI - Systemic allergic dermatitis caused by diltiazem.
PMID- 28497626
TI - Allergic contact dermatitis caused by cobalt in leather - clinical cases.
PMID- 28497628
TI - Successful patch testing of a patient receiving anti-interleukin-17 therapy with
secukinumab: a case report.
PMID- 28497627
TI - Allergic contact stomatitis caused by neem leaves (Azadirachta indica).
PMID- 28497629
TI - The attitude of patients with p-phenylenediamine or 2,5-toluenediamine contact
allergy to hair dyeing.
PMID- 28497630
TI - Acute generalized exanthematous pustulosis caused by an iodinated contrast
radiocontrast medium for computed tomography arthrography of the knee.
PMID- 28497631
TI - The European nickel regulation and changes since its introduction.
PMID- 28497632
TI - Acute generalized exanthematous pustulosis (AGEP) induced by azithromycin.
PMID- 28497633
TI - Allergic contact dermatitis caused by poly(hexamethylene) biguanide hydrochloride
in contact lens care solutions.
PMID- 28497635
TI - Contact allergy to reactive dyes in footwear.
PMID- 28497634
TI - Allergic contact dermatitis caused by cetearyl isononanoate in a sunscreen
product.
PMID- 28497636
TI - Contact allergy to thioctic acid present in Hypromellose(r) eye drops.
PMID- 28497637
TI - Successful use of rivaroxaban in inferior vena cava thrombosis provoked by
multiple traumatic injuries and surgeries: A case report.
AB - WHAT IS KNOWN AND OBJECTIVES: There is a lack of consensus regarding optimal
anticoagulation regimen and duration for inferior vena cava (IVC) thrombus due to
the paucity of clinical evidence. A case of IVC thrombus treated with 3 months of
rivaroxaban therapy is reported. CASE DESCRIPTION: Fifty-two-year-old male
Caucasian presented following a motorcycle accident, with multiple left rib
fractures requiring emergent amputation surgeries. During the hospitalization, he
developed IVC thrombosis and completed 3 months of rivaroxaban treatment without
any complication. The Doppler images at 6-week, 3-month and 6-month follow-up
appointments showed no IVC thrombosis. WHAT IS NEW AND CONCLUSION: This is the
first case of IVC thrombosis successfully treated with rivaroxaban. Further case
series and clinical studies are needed to guide the use of direct oral
anticoagulants for IVC thrombosis.
PMID- 28497638
TI - Bounding the causal effect of unemployment on mental health: Nonparametric
evidence from four countries.
AB - An important, yet unsettled, question in public health policy is the extent to
which unemployment causally impacts mental health. The recent literature yields
varying findings, which are likely due to differences in data, methods, samples,
and institutional settings. Taking a more general approach, we provide comparable
evidence for four countries with different institutional settings-Australia,
Germany, the UK, and the United States-using a nonparametric bounds analysis.
Relying on fairly weak and partially testable assumptions, our paper shows that
unemployment has a significant negative effect on mental health in all countries.
Our results rule out effects larger than a quarter of a standard deviation for
Germany and half a standard deviation for the Anglo-Saxon countries. The effect
is significant for both men and women and materialises already for short periods
of unemployment. Public policy should hence focus on early prevention of mental
health problems among the unemployed.
PMID- 28497639
TI - Functionalization of P4 through Direct P-C Bond Formation.
AB - Research on chlorine-free conversions of P4 into organophosphorus compounds
(OPCs) has a long track record, but methods that allow desirable, direct P-C bond
formations have only recently emerged. These include the use of metal organyls,
carbenes, carboradicals, and photochemical approaches. The versatile product
scope enables the preparation of both industrially relevant organophosphorus
compounds, as well as a broad range of intriguing new compound classes. Herein we
provide a concise overview of recent breakthroughs and outline the acquired
fundamental insights to aid future developments.
PMID- 28497640
TI - Polarizable crystals in apocrine sweat gland tumors: A series of 3 cases.
AB - Polarizable calcium oxalate (CaOx) crystals have been well documented in breast
biopsies, generally associated with benign apocrine metaplasia. In contrast,
polarizable crystals are only rarely reported in skin adnexal neoplasms. We
report 3 different cases of sweat gland tumors with polarizable crystals
morphologically suggestive of CaOx: 1 apocrine hidrocystoma and 2 tubular
apocrine adenomas. The histologic features were examined in 3 cases. Clinical
presentation summary included 2 males and 1 female, ages 53 to 74 years, with
lesions located on the left cheek, inferior vertex scalp and the left eyebrow.
All 3 cases showed polarizable, geometric, plate-like and fractured, colorless
crystals within the lumens of the neoplasm. Of note, these crystals were seen
only on the toluidine blue-stained section of Case #1, but were not present on
the corresponding permanent section. We hypothesize that polarizable crystals may
be present in sweat gland neoplasms more often than previously documented, but
that they may often dissolve with routine processing, accounting for their rare
visibility. We highlight this rare finding, and suggest that it may be
underreported. We only noted this finding in benign apocrine tumors; further
investigation would be necessary to determine whether these crystals are also
seen in other cutaneous adnexal neoplasms.
PMID- 28497641
TI - Adult executive functioning inventory (ADEXI): Validity, reliability, and
relations to ADHD.
AB - This study examined the psychometric properties of the Adult Executive
Functioning Inventory (ADEXI). This new executive functioning (EF) rating
instrument has the advantage of being brief (14 items) and focusing specifically
on working memory and inhibitory control. Results showed that scores on the ADEXI
had high internal consistency and adequate test-retest reliability, but low
concurrence between self-ratings and other ratings. High and statistically
significant correlations were found between ADEXI scores and scores from another
EF rating instrument, whereas the correlations between ADEXI scores and
neuropsychological test scores were weak and often non-significant. Furthermore,
with regard to discriminant validity, individuals with attention deficit
hyperactivity disorder (ADHD) had significantly higher scores on both the
inhibition and working memory subscales compared to clinical as well as non
clinical controls. The results showed high specificity, but relatively low
sensitivity, when discriminating between adults with ADHD and non-clinical
controls. Conclusively, the ADEXI can be a valuable screening instrument for
assessing deficits in working memory and inhibitory control. However, similarly
to other EF ratings, the ADEXI should be used as a complement rather than as a
replacement for neuropsychological tests, and the low interrater reliability
suggests that ratings from multiple sources is preferable compared to relying
solely on self-ratings.
PMID- 28497642
TI - Estimating lifetime medical costs from censored claims data.
AB - Claims databases consisting of routinely collected longitudinal records of
medical expenditures are increasingly utilized for estimating expected medical
costs of patients with a specific condition. Survival data of the patients of
interest are usually highly censored, and observed expenditures are incomplete.
In this study, we propose a survival-adjusted estimator for estimating mean
lifetime costs, which integrates the product of the survival function and the
mean cost function over the lifetime horizon. The survival function is estimated
by a new algorithm of rolling extrapolation, aided by external information of age
and sex-matched referents simulated from national vital statistics. The mean
cost function is estimated by a weighted average of mean expenditures of patients
in a number of months prior to their death, of which the number could be
determined by observed costs in their final months, and the weights depend on
extrapolated hazards. We evaluate the performance of the proposed approach in
comparison with that of a popular method using simulated data under various
scenarios and 2 cohorts of intracerebral hemorrhage and ischemic stroke patients
with a maximum follow-up of 13 years and conclude that our new method estimates
the mean lifetime costs more accurately.
PMID- 28497643
TI - Three-dimensional ultrashort echo time MRI and Short T2 images generated from
subtraction for determination of tumor burden in lung cancer: Preclinical
investigation in transgenic mice.
AB - PURPOSE: To investigate the potential of 3D ultrashort echo time MRI and short T2
images generated by subtraction for determination of total tumor burden in lung
cancer. METHODS: As an animal model of spontaneously developing non-small cell
lung cancer, the K-rasLA1 transgenic mouse was used. Three-dimensional MR imaging
was performed with radial k-space acquisition and echo times of 20 us and 1 ms.
For investigation of the short T2 component in the recorded signal, subtraction
images were generated from these data sets and used for consensus identification
of tumors. Next, manual segmentation was performed on all MR images by two
independent investigators. MRI data were compared with the results from
histologic investigations and among the investigators. RESULTS: Tumor number and
total tumor burden from imaging experiments correlated strongly with the results
of histologic investigations. Intra- and interuser comparison showed highest
correlations between the individual measurements for ultra-short TE MRI.
CONCLUSIONS: Three-dimensional MRI protocols facilitate accurate tumor
identification in mice harboring lung tumors. Ultrashort TE MRI is the superior
imaging strategy when investigating lung tumors of miscellaneous size with 3D MR
imaging strategies. Magn Reson Med 79:1052-1060, 2018. (c) 2017 International
Society for Magnetic Resonance in Medicine.
PMID- 28497644
TI - Cost of illness of non-alcoholic liver cirrhosis in Japan: A time trend analysis
and future projections.
AB - AIM: Liver cirrhosis is a preneoplastic condition to hepatocellular carcinoma
that is an important worldwide public health concern, and its economic burden has
been estimated in some countries. The objective of this study was to estimate and
predict the cost of illness (COI) associated with non-alcoholic liver cirrhosis
in Japan. METHODS: Using a COI method on available data from government
statistics, we estimated the economic burden in 3-year intervals from 1996 to
2014. We then predicted the COI in 3-year intervals from 2017 to 2029 using fixed
and variable model estimations. With fixed model estimation, only the estimated
future population was used as a variable. Variable model estimation considered
the time trends of health-related indicators throughout the past 18 years.
RESULTS: The estimated COI of non-alcoholic liver cirrhosis was Y208.1bn in 2014.
The COI of non-alcoholic liver cirrhosis had a downward trend from 1996 to 2014.
The predicted future COI of non-alcoholic liver cirrhosis was Y144.3-210.5bn,
Y106.0-213.8bn, Y88.6-213.4bn, Y76.7-215.5bn, and Y66.4-214.3bn in 2017, 2020,
2023, 2026, and 2029, respectively. CONCLUSIONS: The results of this study
suggest that the COI of non-alcoholic liver cirrhosis in Japan has steadily
decreased and will continue to decrease. Treatment of patients with hepatitis C
virus infection with newly introduced technologies has high therapeutic
effectiveness, which will affect the future prevalence of non-alcoholic liver
cirrhosis. When interpreting the results of long-term estimation, it should be
noted that the results of this study were based on present conditions.
PMID- 28497645
TI - Peptic ulcer bleeding patients with Rockall scores >=6 are at risk of long-term
ulcer rebleeding: A 3.5-year prospective longitudinal study.
AB - BACKGROUND AND AIM: Patients with high Rockall scores have increased risk of
rebleeding and mortality within 30 days after peptic ulcer bleeding, but long
term outcomes deserve follow-up after cessation of proton pump inhibitors. The
paper aimed to validate whether patients with high Rockall scores have more
recurrent ulcer bleeding in a 3.5-year longitudinal cohort. METHODS: Between
August 2011 and July 2014, 368 patients with peptic ulcer bleeding were
prospectively enrolled after endoscopic hemostasis to receive proton pump
inhibitors for at least 8 to 16 weeks. These subjects were categorized into
either a Rockall scores >=6 group (n = 257) or a Rockall scores <6 group (n =
111) and followed up until July of 2015 to assess recurrent ulcer bleeding.
RESULTS: The proportion of patients with rebleeding during the 3.5-year follow-up
was higher in patients with Rockall scores >=6 than in those with scores <6
(10.51 vs. 3.63 per 100 person-year, P = 0.004, log-rank test). Among patients
with Rockall scores >=6, activated partial thromboplastin time prolonged >=1.5
fold (P = 0.045), American Society of Anesthesiologists physical status class
>=III (P = 0.02), and gastric ulcer (P = 0.04) were three additional independent
factors found to increase rebleeding risk. The cumulative rebleeding rate was
higher in patients with Rockall scores >=6 with more than or equal to any two
additional factors than in those with fewer than two additional factors (15.69
vs. 7.63 per 100 person-year, P = 0.012, log-rank test). CONCLUSIONS: Patients
with Rockall scores >=6 are at risk of long-term recurrent peptic ulcer bleeding.
The risk can be independently increased by the presence of activated partial
thromboplastin time prolonged >=1.5-fold, American Society of Anesthesiologists
class >=III, and gastric ulcer in patients with Rockall scores >=6.
PMID- 28497646
TI - Azole-resistant Aspergillus fumigatus in sawmills of Eastern France.
AB - AIMS: Emergence of azole-resistant Aspergillus fumigatus complicates management
of Aspergillus diseases. Currently, selection pressure caused by azole fungicide
use in farming is strongly suspected of creating resistance. As sawmills also use
azole fungicides, we investigated the presence of azole-resistant strains in this
environment and studied the relationship between azole fungicide use and
development of resistance. METHODS AND RESULTS: Air (n = 200) and substrate (n =
600) samples were taken in 20 sawmills. Azole-resistant strains (Etest and EUCAST
methods) were confirmed by sequencing the cyp51A gene and its promoters. Dosage
of propiconazole and tebuconazole was performed by gas chromatography coupled
with mass spectrometry. Twenty-four azole-resistant A. fumigatus strains were
collected among 20 of the 600 substrate samples (3%). Eighty-three percent of
theses strains had TR34 /L98H mutation. A significantly higher number of
resistant strains was collected in sawmills using fungicide products made with
propiconazole mixed with a high concentration of tebuconazole (P = 0.009). The
presence of resistant strains was significantly linked to propiconazole
quantities in substrates (P = 0.03). CONCLUSIONS: The outcome of azole-resistant
A. fumigatus carrying TR34 /L98H mutation seems to greatly depend on the azole
fungicide formulation and quantities of azole. These preliminary results are
valuable to propose new approaches limiting the emergence of azole-resistant
strains. SIGNIFICANCE AND IMPACT OF THE STUDY: Azole resistance is an emerging
problem in A. fumigatus and threatens clinical advances made possible by the use
of azole antifungals in the treatment of Aspergillus-related diseases. Azole
fungicides are also used in the wood industry, notably in sawmills, to protect
wood from wood-destroying fungi. Through our study, we show that sawmills
represent another professional environment affected by the presence of azole
resistant A. fumigatus strains carrying the TR34 /L98H mutation. Moreover, this
study provides valuable preliminary results to propose some new approaches to
limit the emergence of azole-resistant A. fumigatus strains.
PMID- 28497647
TI - Synthesis, Structure, and Reactivity of Ga-Substituted Distibenes and Sb
Analogues of Bicyclo[1.1.0]butane.
AB - Monovalent gallanediyl LGa {L=HC[C(Me)N(2,6-iPr2 C6 H3 )]2 } reacts with SbX3 to
form the Ga-substituted distibenes [(LGaX)2 Sb2 ] (X=NMeEt 1, Cl 2). Upon
heating, 2 reacts to the bicyclo[1.1.0]butane analogue [(LGaCl)2 (MU,eta1:1 -Sb4
)] 3 containing a [Sb4 ]2- dianion. Moreover, 2 reacts with Li amides LiNR2 in
salt elimination reactions that form the corresponding amido-substituted
compounds 1 and [(LGaNMe2 )2 Sb2 ] 4, whereas reactions of 4 and [(LGaNMe2 )2
(MU,eta1:1 -Sb4 )] 5 with two equivalents of GaCl3 resulted in the formation of 2
and 3, respectively. 1, 2 and 3 were characterized by 1 H and 13 C NMR
spectroscopy, elemental analysis, and single crystal X-ray diffraction. In
addition, their bonding situation was analyzed by quantum chemical calculations.
PMID- 28497648
TI - Intrahepatic cholangiojejunostomy for complex biliary stenosis after pediatric
living-donor liver transplantation.
AB - The treatment of biliary stenosis after pediatric LDLT is challenging. We
describe an innovative technique of peripheral IHCJ for the treatment of patients
with complex biliary stenosis after pediatric LDLT in whom percutaneous treatment
failed. During surgery, the percutaneous biliary drainage is removed and a
flexible metal stylet is introduced trough the tract. Subsequently, the most
superficial aspect of the biliary tree is recognized by palpation of the stylet's
round tip in the liver surface. The liver parenchyma is then transected until the
bile duct is reached. A side-to-side anastomosis to the previous Roux-en-Y limb
is performed over a silicone stent. Among 328 pediatric liver transplants
performed between 1988 and 2015, 26 patients developed biliary stenosis. From
nine patients requiring surgery, three patients who had received left lateral
grafts from living-related donors due to biliary atresia were successfully
treated with IHCJ. After a mean of 45.6 months, all patients are alive with
normal liver morphological and function tests. The presented technique was a
feasible and safe surgical option to treat selected pediatric recipients with
complex biliary stenosis in whom percutaneous procedures or rehepaticojejunostomy
were not possible, allowing complete resolution of cholestasis and thus avoiding
liver retransplantation.
PMID- 28497649
TI - Lanthanide Complexes that Respond to Changes in Cyanide Concentration in Water.
AB - Cyanide ions are shown to interact with lanthanide complexes of phenacylDO3A
derivatives in aqueous solution, giving rise to changes in the luminescence and
NMR spectra. These changes are the consequence of cyanohydrin formation, which is
favored by the coordination of the phenacyl carbonyl group to the lanthanide
center. These complexes display minimal affinity for fluoride and can detect
cyanide at concentrations less than 1 MUm. By contrast, lanthanide complexes with
DOTAM derivatives display no affinity for cyanide in water, but respond to
changes in fluoride concentration.
PMID- 28497650
TI - Permanent Genetic Resources added to Molecular Ecology Resources Database 1 April
2013-31 May 2013.
PMID- 28497651
TI - Harnessing the power of digital droplet PCR to conduct real-world microbial
competitions.
AB - The budding yeast, Saccharomyces cerevisiae, has a long and storied history as a
model organism for genetic, cellular and molecular biological research. More
recently, researchers have sought to understand the ecology and evolution of its
sister species, Saccharomyces paradoxus, in part to put our vast knowledge of the
model yeast into its natural context (Replansky et al. ). However, the research
tools have been limited, and most investigations into natural populations have
either been descriptions of patterns of biogeography or taken the organism back
into the laboratory for mating, growth and competition assays (Kuehne et al. ;
Miller & Greig ; Murphy & Zeyl ; Samani et al. ). The link between what occurs
out in the real world and what is measured in the laboratory has not yet been
made, as so much is still unknown about the natural history of these yeasts. In
this issue of Molecular Ecology Resources, Boynton et al. () take a major step
towards bridging laboratory studies with field ecological research. By isolating
a panel of S. paradoxus strains from a wooded area, culturing them in the
laboratory, reintroducing pairs back into their habitat on natural substrate and
monitoring the frequency of individual strains using digital droplet PCR, the
researchers were able to use the framework of laboratory-based microbial
competitions, but conduct them in a natural setting. While there is still more to
learn about how to optimize this approach, it represents an exciting step in
microbial ecological research and should prove an important tool for other
species and numerous ecological questions.
PMID- 28497652
TI - An isoflavone enriched diet increases skeletal muscle adaptation in response to
physical activity in ovariectomized rats.
AB - SCOPE: This study was to investigate anabolic adaptation of skeletal muscle in
response to an isoflavone (ISO) enriched diet, training and their combinations in
ovariectomized (OVX) rats. METHODS AND RESULTS: Female Wistar rats were
sedentary, performed treadmill uphill running, received ISOs, or a combination of
ISOs and running after ovariectomy. Body weight was increased by OVX. Both ISO
and training treatment antagonized this increase. The weights of soleus and
gastrocnemius muscles were increased only when training and ISOs were combined.
In soleus muscle insulin-like growth factor (IGF)-1R, MyoD and Myogenin
expressions were only up-regulated by training in Sham groups. However, a
stimulation of IGF-1R and MyoD expression could be observed when ISOs and
training were combined. In gastrocnemius muscle MyoD and Myogenin expressions
were stimulated by either training or ISOs. Additive effects were detected when
combining the two interventions. CONCLUSION: Our results indicate that the
combination of ISOs and exercise is more efficient in increasing relative
skeletal muscle mass and the expression of molecular markers related to anabolic
adaptation in the skeletal muscle of female rats.
PMID- 28497653
TI - Reply to Comment on "Flexible Asymmetric Supercapacitors Based on Nitrogen-Doped
Graphene Hydrogels with Embedded Nickel Hydroxide Nanoplates".
AB - In this reply to the Comment by Dr. Sascha Vongehr, the other authors of
"Flexible Asymmetric Supercapacitors Based on Nitrogen-Doped Graphene Hydrogels
with Embedded Nickel Hydroxide Nanoplates" present a rebuttal and clarify their
interpretations of the issues he raised, arguing that numerous surmises and
misinterpretations were made in the previous Comment.
PMID- 28497655
TI - Nicotine self-administration reverses cognitive deficits in a rat model for
schizophrenia.
AB - High comorbidity between schizophrenia and tobacco addiction has been well
established. Explanatory theories include nicotine as a cognitive enhancer
ameliorating symptoms of schizophrenia and underlying shared substrates
increasing susceptibility to addiction in these individuals. To test these non
mutually exclusive theories, the maternal immune activation (MIA) model was
utilized. To this end, pregnant Sprague Dawley rats were subcutaneously injected
with a bacterial endotoxin, lipopolysaccharide (0.5 mg/kg), on gestation days 10
and 11. Selective attention and working memory in adult male offspring were
subsequently assessed using the latent inhibition and delayed non-matching to
sample paradigms both before and after nicotine or saline self-administration.
MIA led to deficits in both latent inhibition and delayed non-matching to sample
in male offspring. Further, these animals showed a small but significantly
increased responding for nicotine during self-administration acquisition,
although there was no difference in dose-response effect or in progressive ratio
testing. However, nicotine, but not saline self-administration, significantly
ameliorated the cognitive deficits induced by MIA. While the male offspring of
mothers prenatally exposed to lipopolysaccharide was only slightly more sensitive
to the reinforcing effects of nicotine, after self-administration, the MIA
induced cognitive deficits significantly improved. These data lend support for
the self-medication hypothesis of schizophrenia.
PMID- 28497654
TI - Oxidative Stickland reactions in an obligate aerobic organism - amino acid
catabolism in the Crenarchaeon Sulfolobus solfataricus.
AB - The thermoacidophilic Crenarchaeon Sulfolobus solfataricus is a model organism
for archaeal adaptation to extreme environments and renowned for its ability to
degrade a broad variety of substrates. It has been well characterised concerning
the utilisation of numerous carbohydrates as carbon source. However, its amino
acid metabolism, especially the degradation of single amino acids, is not as well
understood. In this work, we performed metabolic modelling as well as metabolome,
transcriptome and proteome analysis on cells grown on caseinhydrolysate as carbon
source in order to draw a comprehensive picture of amino acid metabolism in S.
solfataricus P2. We found that 10 out of 16 detectable amino acids are imported
from the growth medium. Overall, uptake of glutamate, methionine, leucine,
phenylalanine and isoleucine was the highest of all observed amino acids. Our
simulations predict an incomplete degradation of leucine and tyrosine to organic
acids, and in accordance with this, we detected the export of branched-chain and
aromatic organic acids as well as amino acids, ammonium and trehalose into the
culture supernatants. The branched-chain amino acids as well as phenylalanine and
tyrosine are degraded to organic acids via oxidative Stickland reactions. Such
reactions are known for prokaryotes capable of anaerobic growth, but so far have
never been observed in an obligate aerobe. Also, 3-methyl-2-butenoate and 2
methyl-2-butenoate are for the first time found as products of modified Stickland
reactions for the degradation of branched-chain amino acids. This work presents
the first detailed description of branched-chain and aromatic amino acid
catabolism in S. solfataricus.
PMID- 28497656
TI - Identification of atypical porcine pestivirus infection in swine herds in China.
AB - Atypical porcine pestivirus (APPV) have been detected in swine herds from the
USA, Germany, the Netherlands, Spain and most recently in Austria, suggesting a
wide geographic distribution of this novel virus. Here, for the first time, we
reported APPV infection in swine herds in China. Newborn piglets from two
separate swine herds in Guangdong province were found showing typical congenital
tremors in July and August 2016. RT-PCR, sequencing and phylogenetic analysis
showed APPV infection occurred. Phylogenetic analysis showed that Chinese APPV
strains, GD1 and GD2, formed independent branch from the USA, Germany and the
Netherlands. Nucleotide identities between members of the APPV ranged between
83.1% and 83.5%, and this showed APPV is highly diverse. It is apparent that this
provides the first molecular evidence of APPV infection in swine herds in China.
PMID- 28497657
TI - A rapid gene sequencing panel strategy to facilitate precision neonatal medicine.
PMID- 28497658
TI - Toxic epidermal necrolysis in a child 6 months post-hematopoietic stem cell
transplantation.
AB - TEN is a rare and critical disease mostly caused by drugs. It is mediated by
activated CD8+ T cells that cause keratinocyte apoptosis with the assistance of
cytokines/chemokines. We herein report a pediatric case of TEN after allogeneic
HSCT with precursor B-cell acute lymphoblastic leukemia (pre-B-ALL) in second
complete remission. Although we did not evaluate the T-cell subpopulation in
blood or skin lesion of the patient, an imbalanced immune reconstitution after
HSCT might additively contribute to the development of TEN.
PMID- 28497659
TI - Complete genome sequence of bluetongue virus serotype 4 that emerged on the
French island of Corsica in December 2016.
AB - In November 2016, sheep located in the south of Corsica island exhibited clinical
signs suggestive of bluetongue virus (BTV) infection. Laboratory analyses allowed
to isolate and identify a BTV strain of serotype 4. The analysis of the full
viral genome showed that all the 10 genomic segments were closely related to
those of the BTV-4 present in Hungary in 2014 and involved in a large BT outbreak
in the Balkan Peninsula. These results together with epidemiological data suggest
that BTV-4 has been introduced to Corsica from Italy (Sardinia) where BTV-4
outbreaks have been reported in autumn 2016. This is the first report of the
introduction in Corsica of a BTV strain previously spreading in eastern Europe.
PMID- 28497660
TI - Chitosan brush for professional removal of plaque in mild peri-implantitis.
AB - BACKGROUND: The aim of the study was to evaluate the effectiveness of a chitosan
brush on the treatment of mild peri-implantitis. METHODS: Fifteen patients
diagnosed with mild peri-implantitis contributing with single implant were
treated with a chitosan brush. Modified plaque index (mPll), Modified Bleeding
Index (mBoP) and probing depth (PPD) were recorded at baseline, 2, 4, 12 and 24
weeks. Chitosan brush was used at 12 weeks if diagnosis was still present.
Periapical radiographs were taken at the beginning of the study and 6 months
after to control the stability of bone level. RESULTS: None of the patients
reported discomfort or side effects during treatment. Bone level was maintained
stable during the entire study. Plaque index remained almost 0 at every control
visit. PPD and mBoP were significantly reduced at 2 weeks and when compared to
baseline. At 24 weeks 73% of patients presented no further bleeding on probing
with stable bone level. CONCLUSIONS: Chitosan brush could be a reliable
instrument for the professionally administered plaque removal and resolution of
clinical signs of initial stages of peri-implant inflammation.
PMID- 28497661
TI - Medication-related osteonecrosis of the jaw: risk factors in patients under
biphosphonate versus patients under antiresorptive-antiangiogenic drugs.
AB - BACKGROUND: Biphosphonate-related osteonecrosis of the jaw (BRONJ) is a potential
side effect associated with the administration of bisphosphonates; the aim of
this work is to highlight the possible epidemiological differences between two
groups of patients affected by medication related osteonecrosis of the jaw
(MRONJ) treated at the Center of Oral Medicine, Pathology and Laser Surgery of
the Academic Hospital at the University of Parma, Italy, between January 2004 and
June 2016. METHODS: Medical charts of 303 patients (214 females and 89 males,
mean age: 67 years old) treated at the Center of Oral Medicine, Pathology and
Laser Surgery of the Academic Hospital at the University of Parma, between
January 2004 and June 2016, were retrospectively analyzed. Patients were divided
in 2 groups according to drugs therapy they underwent: group 1 (G1) including
patients treated with bisphosphonates alone and group 2 (G2) including patients
receiving antiresorptive-antiangiogenic drugs in association with bisphosphonates
or antiresorptive-antiangiogenic drugs alone. Than 269 MRONJ sites treated with 5
different therapeutical approaches were analyzed. RESULTS: Results showed G1
consisting mainly in female patients undergoing bisphosphonates for oncologic
disease, stage II was most frequently diagnosed and MRONJ developed mainly after
dental extraction or bone surgery. G2 consisted mainly in males patients, whom
took antiresorptive-antiangiogenic drugs in association with bisphosphonate or
antiresorptive-antiangiogenic drugs alone for oncologic disease. Stage II was
most frequently diagnosed and MRONJ developed most frequently "spontaneous".
CONCLUSIONS: This study showed how a new population affected by MRONJ is
emerging. Men affected by kidney cancer treated with new antiresorptive
antiangiogenic drugs will represent a growing portion of the pool of patients at
risk. In our experience, a strict follow-up is of outmost importance to early
detect MRONJ also in patients with spontaneous cases. When MRONJ occurs, surgical
laser treatment with Er:YAG seems to represent the option with highest percentage
of success; for patients with contraindication to surgery, LLLT helps to improve
outcomes of the medical therapy.
PMID- 28497662
TI - Volatile sulphur compounds in exhaled air of dental students smoking the
waterpipe: a nested case control study.
AB - BACKGROUND: This study aims at investigating a potential adverse effect that
waterpipe tobacco smoking may cause by comparing levels of volatile sulphur
compounds in exhaled air of male dental students who smoke the waterpipe with
those who do not smoke. METHODS: Dental students were categorized into waterpipe
smokers and non-smokers. Volatile sulphur compounds were measured using a
halimeter following the completion of questionnaire on smoking and oral hygiene
habits and self-perceived halitosis. Statistics were carried out using ANOVA and
relevant post hoc tests, associations were investigated using cross tabulation
with the chi2 test. RESULTS: Results showed significantly higher levels of
volatile sulphur compounds in: waterpipe smokers who smoke at least once a month
when compared with non-smokers regardless their oral hygiene habits; subjects who
do not brush their teeth; and subjects who self-perceive halitosis. There were no
significant differences in these levels for similar groups on the basis of: use
of floss, or use of mouth wash. CONCLUSIONS: It seems that waterpipe tobacco
smoking results in increased volatile sulphur compounds levels in exhaled air.
Oral hygiene practices like the use of tooth brush, dental floss, and mouth wash
also seem to result in lower levels.
PMID- 28497663
TI - Mortality risk prediction models for coronary artery bypass graft surgery:
current scenario and future direction.
AB - INTRODUCTION: Many risk prediction models are currently in use for predicting
short-term mortality following coronary artery bypass graft (CABG) surgery. This
review critically appraised the methods that were used for developing these
models to assess their applicability in current practice setting as well as for
the necessity of up-gradation. EVIDENCE ACQUISITION: Medline via Ovid was
searched for articles published between 1946 and 2016 and EMBASE via Ovid between
1974 and 2016 to identify risk prediction models for CABG. Article selection and
data extraction was conducted using the CHARMS checklist for review of prediction
model studies. Association between model development methods and model's
discrimination was assessed using Kruskal-Wallis one-way analysis of variance and
Mann-Whitney U-test. EVIDENCE SYNTHESIS: A total of 53 risk prediction models for
short-term mortality following CABG were identified. The review found a wide
variation in development methodology of risk prediction models in the field.
Ambiguous predictor and outcome definition, sub-optimum sample size,
inappropriate handling of missing data and inefficient predictor selection
technique are major issues identified in the review. Quantitative synthesis in
the review showed "missing value imputation" and "adopting machine learning
algorithms" may result in better discrimination power of the models. CONCLUSIONS:
There are aspects in current risk modeling, where there is room for improvement
to reflect current clinical practice. Future risk modelling needs to adopt a
standardized approach to defining both outcome and predictor variables, rational
treatment of missing data and robust statistical techniques to enhance
performance of the mortality risk prediction.
PMID- 28497664
TI - Insulin sensitizers in adolescents with polycystic ovary syndrome.
AB - Polycystic ovary syndrome (PCOS) is the most common disorder of androgen excess
in women of reproductive age. The diagnosis of PCOS can be more challenging in
adolescents than in adult women given significant overlap between normal puberty
and the signs of PCOS, including acne, menstrual irregularity, and polycystic
ovarian morphology. Optimal treatments for adult women with PCOS vary depending
on patient risk factors and reproductive goals, but mainly include hormonal
contraception and insulin sensitizers. There is continued interest in targeting
the intrinsic insulin resistance that contributes to metabolic and hormonal
derangements associated with PCOS. The vast majority of published data on insulin
sensitizing PCOS treatments are reported in adult women; these have included
weight loss, metformin, thiazolidinediones, and the inositols. Furthermore, there
is also a small but growing body of evidence in support of the use of insulin
sensitizers in adolescents, with or without oral contraceptives. Discussion of
the available treatments, including benefits, potential side effects, and
incorporation of patient and family preferences is critical in developing a plan
of care aimed at achieving patient-important improvements in PCOS signs and
symptoms while addressing the longer-term cardiometabolic risks associated with
the syndrome.
PMID- 28497665
TI - Preoperative staging of rectal cancer using magnetic resonance imaging:
comparison with pathological staging.
AB - BACKGROUND: The aim of this study was to evaluate the accuracy of magnetic
resonance (MR) in loco-regional staging of rectal cancer by comparing the MR
results with histologic findings, considered as standard reference. METHODS:
Between July 2013 and March 2015, fifty-two patients, 27 (51.9%) males, age
66.75+/-13.77 years, with rectal cancer, were staged preoperatively with MR and
proceeding straight to surgery. Two observers with experience in abdominal MR
independently reviewed the images. T stage and N stage were evaluated according
to the 7th edition of TNM classification. The estimate of Ln probability of
malignancy (low, moderate, high) was based on nodal size, border contour and
signal intensity and comparison between ADC value of the Ln's belonging to the
three different classifications were performed. Statistical testing included
Cohen's kappa coefficient, Mann-Whitney's, Kruskal-Wallis, chi2, Fisher's Exact
Test and Receiving Operating Characteristics curve. RESULTS: MR correctly
assessed T stage in 47/52 cases (90.4%; kw=0.89+/-0.06), with inter-operator
concordance of k=0.81+/-0.08. For Ln staging, concordance between estimate of
high probability malignancy and pathology was kw=0.62+/-0.11. ADC was
significantly different for the three grades of estimated malignancy probability
(P=0.0003), decreasing from 1.227+/-0.298*10-3 mm2/s (low) to 1.120+/-0.306*10-3
mm2/s (moderate) and finally to 0.818+/-0.168*10-3 mm2/s (high). The ROC curve
procedure established the good ability of ADC to discriminate high malignancy
Ln's (AUC=0.88) with cut-off at <1*10-3 mm2/s. The percentage of high malignancy
Ln's in the lateral pelvic space was higher than in other sites (55.6% vs. 17.6%,
P=0.0003). CONCLUSIONS: MR is an accurate imaging method in T staging and N
staging of rectal cancer: prediction of N was improved by considering dimension,
morphology and signal characteristic and the ability of ADC to identify high
probability malignant nodes underlines its importance in the diagnostic process.
PMID- 28497666
TI - Serious dysphagia following anterior cervical discectomy and fusion: long-term
incidence in a national cohort.
AB - BACKGROUND: Although dysphagia is often self-limiting after anterior cervical
discectomy and fusion (ACDF), its incidence, risks, and long-term outcomes remain
unclear. The present study aimed to analyze dysphagia up to 5 years post-ACDF
using a nation-scaled cohort. METHODS: Incidences of permanent dysphagia
requiring nasogastric-tube feeding after ACDF were analyzed using three million
sample cohorts derived from the National Health Insurance Research Database of
Taiwan. All identified subjects were stratified into four groups (40s, 50s, 60s,
and >70) according to their age at operation, and were subsequently followed up
for 5 years. The risks of dysphagia were compared between the groups using Kaplan
Meier analysis and Cox regression hazard ratio model. RESULTS: A total of 2,723
patients (> 40 years old) who received first-time ACDF surgery were identified
from a cohort of three million and followed up for a maximum of 5 years post
operation. The 5-year incidence rates of persistent dysphagia (requiring use of a
nasogastric tube) were 6.1, 4.0, 12.0, and 22.8 per 1,000 person-years for each
age group (40s, 50s, 60s, and 70+ years old, respectively). The overall incidence
rate of dysphagia after ACDF was 18.4, 10.9, and 8.9 per 1,000 person-years at 3
months, 1 year, and 5 years follow-up, respectively. The incidence rates of
dysphagia and use of home care services were highest at 3 months post-operation
in all age groups, but dropped to a stable level after one year post-operation.
The risks of dysphagia and the necessity of using home care services were higher
(hazard ratio= 2.69 and 4.96) in the elderly group (aged 70 years and over) at
all follow-up time points. CONCLUSION: The elderly patients had higher risks of
short- and long-term severe dysphagia after ACDF. Therefore, although the
incidence rates were still low (approximately 2.3%), older patients (aged 70
years and over) should be cautioned for dysphagia requiring a nasogastric tube
and home care services if they undergo ACDF.
PMID- 28497667
TI - Midline Lumbar Fusion with cortical bone trajectory as first line treatment in a
selected series of patients with lumbar instability.
AB - OBJECT: Aim of the present study was to proof that for certain complex spinal
conditions, MIDLIF technique is very convenient in terms of length of
hospitalization, functional recovery and pain relief and time to back to work.
METHODS: MIDLF indications were set for patients with not more than 3 unstable
levels, presence of osteoporosis (alternative to cemented screws), or
cardiomyopathy with anticoagulation with or without spinal stenosis, and or
discopathy. Surgical difficulties, operative time, hemoglobin loss and
postoperative 45 days, 6 months and one-year follow- up data are shown. RESULTS
AND CONCLUSIONS: In one-year period MIDLF was applied for 9 patients. For all
cases motor deficits improved, pain decreased from a high VAS score to VAS 1. No
complications were seen so far. In one case small pedicles prevented the use of
MIDLF technique. Operative time, acceptable hemoglobin loss, short length of stay
and encouraging follow-up result indicate that this technique is a valid option
to improve patient's quality of life where osteoporosis makes traditional trans
pedicular screws less stable or where the surgeon has the need to reduce
intraoperative blood loss or has to work in a deep surgical field.
PMID- 28497668
TI - Potential brain dead organ donation in neurocritical care mortality.
AB - BACKGROUND: Mortality is a marker of quality in neurocritical care, but it also
provides potential for donors after brain death (DBD) following irreversible
acute brain damage. The aim of this study was to analyse the neurointensive care
unit (NICU) mortality rate and recovery of potential DBD. METHODS: We performed a
10-year prospective observational cohort computer database analysis of 6138 acute
neurological and neurosurgical patients (pts, 58.2% male, mean: age 55.9+/-14.7
years, body weight 78.3+/-15.6 kg, body mass index 26.9+/-4.7, NICU stay 3.8+/
5.3 days): 3462 (56.4%) pts with brain disease (mostly stroke 43.2%, tumour
31.1%, trauma 13.6%); 10.3% pts with internal carotid artery (ICA) stenosis;
32.6% pts with spine diseases, and others. Mean Acute Physiology and Chronic
Health Evaluation (APACHE) II score on admission was 10.63+/-5.2 and Glasgow Coma
Scale on admission was 13.79+/-2.51. RESULTS: There were 159 (2.6%) cases of
mortality with a significantly higher mortality rate in pts with brain diseases
(95.6% of deceased pts, p<0.001) than in ICA stenosis (0.6%), spine (1.9%) and
from others (1.9%). There were 23 (14.5%) pts with clinical signs of brain death,
of whom 13 (56.5%) became donors. The main reasons for non-recovery of potential
donors were hemodynamic instability (16.7%) and family reluctance (12.5%).
CONCLUSIONS: The study showed that our NICU mortality was 2.6%. There were
relatively few clinical signs of brain death and not all potential donors were
recovered.
PMID- 28497669
TI - Mapping seizure foci and tumor genetic factors in glioma associated seizure
patients.
AB - BACKGROUND: Epilepsy, which is the most common symptom accompanying gliomas, was
reported as an independent favorable prognosis factor for glioma patients.
However, the correlation between glioma location and epilepsy prognosis, genesis
and genetic phenotypes of the glioma associated seizure (GAS) patients is far
from clear, the purpose of the current study was to provide probabilistic
radiographic atlases reflecting seizure susceptible regions, relationship between
tumor associated biomarkers and seizure initiation and poor epilepsy prognosis
areas. METHODS: Preoperative MRIs were collected from 119 newly diagnosed
patients with histologically confirmed gliomas. These samples were analyzed for
seizure status and tumor genetic makers (TP53 mutations, MMP-9.PTEN, MGMT, EGFR
and IDH1) using a statistical voxel-based lesion-symptom mapping (VLSM) method.
RESULTS: We found bilaterally that the frontal lobe containing regions were
associated with GAS for low grades gliomas, moreover lesions with the PTEN
mutation and IDH1 mutation and seizure susceptible regions were located close
together and partially overlapped, Patients with preoperative tumor involving the
right frontal lobe may have good seizure control; however, for the glioma
infiltrated regions in front of the precentral regions in the left hemisphere,
the epilepsy prognosis is poor. CONCLUSIONS: The current results of seizure
associated molecules and specific regions on structural MRI could be used in
preoperative surgical planning, seizure prognosis predictions and anti-epilepsy
drug usage.
PMID- 28497670
TI - The role of diffusion tensor imaging in assessing the microstructural integrity
of white matter in spinal cord concussions.
PMID- 28497671
TI - Perceived efficacy and satisfaction of patients with subcutaneous hypoallergenic
high-dose house dust mite extract.
AB - Summary: The efficacy and safety of subcutaneous immunotherapy with modified,
high-dose, major allergen house dust mite extract is widely supported by double
blind, placebo-controlled studies. However, little is known regarding patient
perceived efficacy and satisfaction. An observational, retrospective, multicentre
study in patients treated with Acaroid(r) was conducted to assess the efficacy
and degree of satisfaction of the patients after the first six months of
treatment with it. All the clinical study procedures were performed according to
the routine clinical practice. This study demonstrates that Acaroid(r) is
effective and well tolerated. The patients' condition demonstrated a clear and
marked improvement in the first 6 months after treatment initiation. Patients
treated with Acaroid(r) were very satisfied, with a correlation to improvement in
patient-perceived symptoms and the administration of treatment by a healthcare
professional.
PMID- 28497672
TI - Allergic and nonallergic rhinitis and skin sensitization to metals: is there a
link?
AB - Summary: Background. Chromium, Cobalt and Nickel are responsible for contact
dermatitis, that is largely prevalent in the general population. They can act
also as irritants in the upper and lower respiratory airways. Also rhinitis
(allergic and nonallergic) is a high prevalence disorder. Both diseases could
share some common inflammatory mechanisms, but the clinical association between
skin sensitization to metals and rhinitis was never studied. Objective. We
assessed the presence of skin sensitization to metals in subjects with rhinitis.
Methods. Patients suffering from rhinitis underwent a standard diagnostic
procedure, including skin testing, nasal endoscopy and nasal cytology. Control
healthy subjects were also included. None of the patients had skin diseases. All
subjects underwent patch test with Chromium, Cobalt and Nickel. Results. None of
the 26 controls had positive skin prick test or nasal cytology. The 82 rhinitis
patients were subdivided into allergic (group A = 27), nonallergic (group B = 31)
and overlapping (group C = 24). The prevalence of positive patch test to metals
was 26% in group A, 45% in group B, 42% in group C and 31% in controls. The
percentage of patch-positive subjects was significantly different between Group A
and B (p = 0.0045; OR: 0.43), Group A and C (p = 0.0186; OR: 0.49), and Group B
and controls (p = 0.0360; OR: 1.85). There was a significant difference between
groups A + controls and B + C. Conclusion. Even in the absence of skin diseases,
the prevalence of sensitization to metals (patch test) is greater in nonallergic
and overlapping rhinitis, as compared to allergic rhinitis and controls.
PMID- 28497673
TI - Body Mass Index and skin reactivity to histamine and Dermatophagoides
pteronyssinus in children and adolescents followed in a pediatric allergy
service.
AB - Summary: Rationale. Recent data suggest that the nutritional status assessed by
body mass index (BMI) is positively associated with skin reactivity to histamine
in children. Objective. To study the relation between BMI and skin reactivity to
histamine and Dermatophagoides pteronyssinus in allergic children and
adolescents. Methods. The medical charts of patients attended in our outpatient
clinic between 2013 and 2014 (n = 972) were evaluated. Only patients with asthma,
allergic rhinitis or wheezing infants sensitized to at least one aeroallergen
were selected: a total of 626 patients (6 months to 19 year-olds; 60.1% male)
were enrolled. Weight (kg), height (m), BMI (weight/height2), and the mean
diameter of the wheals induced by histamine (10 mg/ml) and Dermatophagoides
pteronyssinus in skin prick tests (SPT) were obtained. Skin index (SI; ratio of
allergen-induced wheal diameter and corresponding histamine diameter) was also
analyzed. Results. All patients had shown a mean wheal diameter of histamine
greater than 1 mm. There was no increased skin reactivity to histamine with
increasing BMI Z score (ZBMI). However, a significant correlation between BMI and
the mean wheal of histamine was observed in patients < -1 ZBMI. Similar results
were observed with Dermatophagoides pteronyssinus, (even considering the SI).
Conclusions. We did not document interference of nutritional status (ZBMI) on the
skin reactivity to histamine or Dermatophagoiodes pteronyssinus in atopic
patients. Further investigation is required.
PMID- 28497674
TI - The Vespid Allergy Quality of Life Questionnaire - cultural adaptation and
translation to Portuguese.
AB - Summary: A cross-cultural translation of the Vespid Allergy Quality of Life
Questionnaire (VQLQ) to the Portuguese population (VQLQ-P) was performed,
assessing its applicability in wasp and in non-beekeeper bee venom allergic
patients. Additionally, we evaluated a Visual Analogue Scale (VAS) to estimate
hymenoptera allergy interference with daily life. Methods. Cross-cultural
translation was performed according to recommendations. The final VQLQ-P version,
the Expectation of Outcome questionnaire (EoQ), EQ-5D and VAS were applied to
wasp (n = 19) and non-beekeeper bee venom allergic patients (n = 30). Results.
VQLQ-P significantly correlated with EoQ, (r = 0.76, p < 0.01), EQ-5D (usual
activities and anxiety / depression dimensions) and VAS, with a good internal
consistency (Cronbach alpha = 0.88) in wasp allergic individuals. VQLQ-P and EoQ
correlation was also high (r = 0.67, p < 0.01) in bee allergy. Conclusion. The
VQLQ-P is a valuable tool to evaluate quality of life impairment in Portuguese
hymenoptera venom allergic individuals.
PMID- 28497675
TI - Evaluation of pulmonary complications in patients with primary immunodeficiency
disorders.
AB - Summary: Background. Primary immunodeficiencies (PIDs) are inherited disorders in
which one or several components of immune system are defected. Moreover, affected
patients are at high risk for developing recurrent infections, particularly
pulmonary infections. The spectrum of pulmonary manifestations in PIDs is broad,
and includes acute and chronic infection, structural abnormalities (eg,
bronchiectasis), malignancy and dysregulated inflammation resulting in tissue
damage. In this study, our aims are to evaluate pulmonary complications in PID
patients. Patients and Methods. We studied 204 cases with confirmed PID. To
evaluate pulmonary complications in these patients, we used pulmonary function
test (PFT), high resolution computed tomography (HRCT) scan and bronchoalveolar
lavage (BAL). Results. Our results showed that pneumonia was the most frequent
clinical manifestations in all PID patients. There were significantly greater
numbers of episodes of pneumonia in HIgM, XLA and CVID patients with delayed
diagnoses < 6 years. Moreover, of 57.4% CVID patients, 55% XLA patients and 33.3%
HIgM patients had abnormal PFT results, and bronchiectasis was showed in 9
(42.9%) of XLA, 6 (11.8%) of HIES, 3 (21.4%) of HIgM and 38 (62.3%) of CVID
patients. Conclusion. Pulmonary complications should be considered in cases with
PIDs especially in CVID cases.
PMID- 28497676
TI - Assessment of validity and reliability of Drug Hypersensitivity Quality of Life
Questionnaire: The Dutch experience.
AB - Summary: Drug Hypersensitivity Quality of Life Questionnaire (DrHy-Q) is the
first questionnaire that captures health related quality of life impact in
patients with drug hypersensitivity. The aim of this study was to translate and
validate the original Italian 15-item DrHy-Q for use among Dutch-speaking
residents. We also compared the DrHy-Q scores obtained across countries. In a
prospective cohort study, the Dutch DrHy-Q was completed by 124 patients (65.3%
female, age 56.8 +/- 14.0) with a confirmed drug hypersensitivity. Median DrHy-Q
score was 12 [0-88]. Validity and reliability of the DrHy-Q was confirmed
through, 1, confirmatory factor analysis; 2, concurrent validity with a generic
health related quality of life questionnaire (RAND-36); 3, internal consistency;
and 4, test-retest reliability. A country specific difference in scores was
observed.
PMID- 28497677
TI - Successful of subcutaneous and oral hyposensitizing therapy in 30 patients.
AB - Summary: Background. Pharmacotherapy and immunotherapy are the main treatment
modalities for respiratory allergy. The aim of this paper has been to evaluate
the efficacy and tolerability of subcutaneous and sublingual immunotherapy in
association in allergic patients, and to demonstrate that the patients who have
performed a second oral vaccination cycle after 4-5 years from the first
subcutaneous treatment, derive benefits that may last for years. This is due to
immune system's plasticity. Methods. The study was conducted in 30 allergic
patients which had previously executed a full cycle of classical subcutaneous
immunotherapy, with a partial remission of symptoms. After 4-5 years, they were
subjected to sublingual immunotherapy for the same allergen, improving the
results obtained. Results. All the patients reported a decrease or absence of
clinical symptoms, a reduction in the use of anti-allergic drugs, and lower
values of PRIST and RAST after the treatment. Conclusions. The results of this
clinical study confirm the improvement of results when subcutaneous and
sublingual immunotherapy are associated.
PMID- 28497678
TI - Eosinophil fungal rhinosinusitis caused by Fusarium infection secondary to
odontogenic maxillary sinus disease: when collaboration between otolaryngologist
and allergologist leads to the correct diagnosis and therapy.
AB - Summary: Rhinitis and sinusitis usually coexist and are concurrent in most
individuals; thus, the correct terminology is now "rhinosinusitis". On the basis
of numerous causative factors, often co-existing in the same patient, the
diagnosis of rhinosinusitis is also made by a wide variety of practitioners
(allergologists, otolaryngologists, pulmonologists, primary care physicians,
paediatricians, and many others). Approximately 5-15% of the population suffers
from chronic rhinosinusitis, and in 10-12% of them, it is of dental origin. The
treatment of odontogenic maxillary sinus disease is directed to the management of
the rhinosinusitis and of the odontogenic source. The widespread use of dental
implants and reconstructive procedures for dental implant placement has led to
new types of complication, as in this case report, due to chronic eosinophilic
rhinosinusitis secondary to Fusarium infection in the maxillary sinus. The
patient was initially evaluated by the allergologist, and subsequently
successfully treated by the otolaryngologist with Functional Endoscopic Sinus
Surgery. The advantages of endoscopic sinus surgery include more accurate
visualization, no external incision, reduced soft tissue dissection, and reduced
hospital stay. Chronic maxillary sinusitis of dental origin is a common disease
that requires treatment of the sinusitis as well as of the odontogenic source.
PMID- 28497679
TI - Disappearance of severe oral allergy syndrome following omalizumab treatment.
AB - Summary: The first case of disappearance of apple-induced oral allergy syndrome
in a birch pollen-allergic patient following omalizumab treatment is reported.
This observation in a case of type 2 food allergy suggests that omalizumab is
potentially an effective preventive treatment for patients with severe, type 1
food allergies.
PMID- 28497680
TI - Guanidinium-Based Polymerizable Surfactant as a Multifunctional Molecule for
Controlled Synthesis of Nanostructured Materials with Tunable Morphologies.
AB - Rationally and efficiently controlling the morphology of nanomaterials plays a
crucial role in significantly enhancing their functional properties and expending
their applications. In this work, a strategy for controlled synthesis of diverse
nanostructured materials with tunable morphologies was developed using a
guanidinium-based surfactant with a polymerizable pyrrole unit as a
multifunctional molecule that can serve not only as a structure-directing agent
for mesostucture formation but also as a monomer and carbon source. The unique
self-assembly behavior of the guanidinium head group under different conditions
allows the synthesized surfactants to form different aggregates and thus to
produce silica nanomaterials with multiple morphologies (such as sphere, disk,
fiber, and cocoon) in conjunction with sol-gel chemistry. Besides the
mesostructured silicates, by further exploring the polymerization and
carbonization features of pyrrole units that were densely packed in the formed
silica nanochannels, diverse nanostructured materials such as mesostructured
conducting polymers, carbon materials, and metal-nanoparticle (NP)-decorated
forms could also be easily obtained in one-pot fashion for various applications,
such as energy storage and catalysis. As a demonstration, carbon nanotubes and Pd
NP-doped hollow carbon spheres were fabricated, which exhibited good specific
capacitance (101.7 F g-1) at the scan rates of 5 mV s-1 and excellent catalytic
performance (100% conversion for three cycles) in the Suzuki C-C coupling
reaction, respectively. All of the results indicate that our strategy may open a
new avenue for efficiently accessing diverse nanostructured materials with
tunable morphologies for wide applications.
PMID- 28497681
TI - pH-Sensitive Delivery Vehicle Based on Folic Acid-Conjugated Polydopamine
Modified Mesoporous Silica Nanoparticles for Targeted Cancer Therapy.
AB - In this study, we introduced a targeting polymer poly(ethylene glycol)-folic acid
(PEG-FA) on the surface of polydopamine (PDA)-modified mesoporous silica
nanoparticles (MSNs) to develop the novel nanoparticles (NPs) MSNs@PDA-PEG-FA,
which were employed as a drug delivery system loaded with doxorubicin (DOX) as a
model drug for cervical cancer therapy. The chemical structure and properties of
these NPs were characterized by transmission electron microscopy, X-ray
photoelectron spectroscopy, N2 adsorption/desorption, dynamic light scattering
autosizer, thermogravimetric analysis, and Fourier transform infrared
spectroscopy. The pH-sensitive PDA coating served as a gatekeeper. The in vitro
drug release experiments showed pH-dependent and sustained drug release profiles
that could enhance the therapeutic anticancer effect and minimize potential
damage to normal cells due to the acidic microenvironment of the tumor. These
MSNs@PDA-PEG-FA achieved significantly high targeting efficiency, which was
demonstrated by the in vitro cellular uptake and cellular targeting assay.
Compared with that of free DOX and DOX-loaded NPs without the folic targeting
ligand, the FA-targeted NPs exhibited higher antitumor efficacy in vivo, implying
that they are a highly promising potential carrier for cancer treatments.
PMID- 28497682
TI - Size-Dependent Regulation of Intracellular Trafficking of Polystyrene
Nanoparticle-Based Drug-Delivery Systems.
AB - Nanoparticles (NPs) have shown great promise as intracellular imaging probes or
nanocarriers and are increasingly being used in biomedical applications. A
detailed understanding of how NPs get "in and out" of cells is important for
developing new nanomaterials with improved selectivity and less cytotoxicity.
Both physical and chemical characteristics have been proven to regulate the
cellular uptake of NPs. However, the exocytosis process and its regulation are
less explored. Herein, we investigated the size-regulated endocytosis and
exocytosis of carboxylated polystyrene (PS) NPs. PS NPs with a smaller size were
endocytosed mainly through the clathrin-dependent pathway, whereas PS NPs with a
larger size preferred caveolae-mediated endocytosis. Furthermore, our results
revealed exocytosis of larger PS NPs and tracked the dynamic process at the
single-particle level. These results indicate that particle size is a key factor
for the regulation of intracellular trafficking of NPs and provide new insight
into the development of more effective cellular nanocarriers.
PMID- 28497683
TI - A Kinetic Pathway toward High-Density Ordered N Doping of Epitaxial Graphene on
Cu(111) Using C5NCl5 Precursors.
AB - Pristine graphene possesses high electrical mobility, but its low charge carrier
density severely limits its technological significance. Past efforts to increase
graphene's carrier density via chemical doping have shown limited successes,
accompanied by substantial reductions in the mobility caused by disordered
dopants. Here, based on first-principles calculations, we propose to grow
graphene on Cu(111) via self-assembly of C5NCl5 molecular precursors to achieve
high-density (1/6) and highly ordered nitrogen doping. Such a process relies on
the elegant concerted roles played by the London dispersion, chemical, and
screened Coulomb repulsive forces in enhancing molecular adsorption, facilitating
easy dechlorination, and dictating the overall orientation of the C5N radicals,
respectively. Further growth from the orientationally correlated graphene islands
is accompanied by significantly minimized density of grain boundaries as the
grains coalesce to form larger N-doped graphene sheets, which are further shown
to possess superb electronic properties for future device applications. Initial
kinetic processes involved in N-doped graphene growth using C5NH5 precursors are
also investigated and contrasted with that of C5NCl5.
PMID- 28497684
TI - Facile Growth of Caterpillar-like NiCo2S4 Nanocrystal Arrays on Nickle Foam for
High-Performance Supercapacitors.
AB - Ternary cobalt nickel sulfide as a novel and efficient electrode material in
supercapacitors has recently gained extensive interests. Herein, we first report
a highly conductive caterpillar-like NiCo2S4, composed of NiCo2S4 nanosheet core
and nanowire shell grown on Ni foam via a facile and cost-effective chemical
liquid process. Growth mechanism of the NiCo2S4 nanosheets@nanowires (NSNWs)
structure was also investigated in detail by analyzing time-dependent
experimental as well as the amount of additive ammonium fluoride in solution.
Furthermore, the electrochemical measurements were performed among three
different morphologies of NiCo2S4 including nanosheets, nanosheets@nanoparticles,
and NSNWs structure, which were obtained from different reaction stages. Because
the NSNWs structure has relatively high electroactive surface area, conductivity,
and effective electron transport pathways, the as-prepared NiCo2S4 NSNWs
structure comparing with two other morphologies exhibits the maximum specific
capacity of 1777 F/g at 1 A/g and the highest capacitance retention (83% after
3000 cycles) at a high scan rate of 10 A/g with a mass loading density of 4.0
mg/cm2. These results indicate that the NiCo2S4 NSNWs structure has great
potential in supercapacitors.
PMID- 28497685
TI - Diastereoselective Synthesis of Chiral 2,3-Disubstituted Indolines via Formal
[3+2]-Cycloaddition of Arynes with gamma-Amino-alpha,beta-unsaturated Esters.
AB - A one step formal [3+2]-annulation protocol for the synthesis of 2,3
disubstituted indolines is described. The in situ generated aryne acts as a two
atom component, and gamma-amino-alpha,beta-unsaturated esters acting as a three
atom component to construct indoline units in a highly regio- and
diastereoselective manner with yields ranging from 63 to 80%.
PMID- 28497686
TI - Enhancing the Durability and Carrier Selectivity of Perovskite Solar Cells Using
a Blend Interlayer.
AB - A mechanically and thermally stable and electron-selective ZnO/CH3NH3PbI3
interface is created via hybridization of a polar insulating polymer,
poly(ethylene glycol) (PEG), into ZnO nanoparticles (NPs). PEG successfully
passivates the oxygen defects on ZnO and prevents direct contact between
CH3NH3PbI3 and defects on ZnO. A uniform CH3NH3PbI3 film is formed on a soft
ZnO:PEG layer after dispersion of the residual stress from the volume expansion
during CH3NH3PbI3 conversion. PEG also increases the work of adhesion of the
CH3NH3PbI3 film on the ZnO:PEG layer and holds the CH3NH3PbI3 film with hydrogen
bonding. Furthermore, PEG tailors the interfacial electronic structure of ZnO,
reducing the electron affinity of ZnO. As a result, a selective electron
collection cathode is formed with a reduced electron affinity and a deep-lying
valence band of ZnO, which significantly enhances the carrier lifetime (473 MUs)
and photovoltaic performance (15.5%). The mechanically and electrically durable
ZnO:PEG/CH3NH3PbI3 interface maintains the sustainable performance of the solar
cells over 1 year. A soft and durable cathodic interface via PEG hybridization in
a ZnO layer is an effective strategy toward flexible electronics and
commercialization of the perovskite solar cells.
PMID- 28497688
TI - Defocused Imaging of UV-Driven Surface-Bound Molecular Motors.
AB - Synthetic molecular motors continue to attract great interest due to their
ability to transduce energy into nanomechanical motion, the potential to do work
and drive systems out-of-equilibrium. Of particular interest are unidirectional
rotary molecular motors driven by chemical fuel or light. Probing the mechanistic
details of their operation at the single-molecule level is hampered by the
diffraction limit, which prevents the collection of dynamic positional
information by traditional optical methods. Here, we use defocused wide-field
imaging to examine the unidirectional rotation of individual molecular rotary
motors on a quartz surface in unprecedented detail. The sequential occupation of
nanomechanical states during the UV and heat-induced cycle of rotation are
directly imaged in real-time. The approach will undoubtedly prove important in
elucidating the mechanistic details and assessing the utility of novel synthetic
molecular motors in the future.
PMID- 28497689
TI - High-Performance Li-Ion Capacitor Based on an Activated Carbon Cathode and Well
Dispersed Ultrafine TiO2 Nanoparticles Embedded in Mesoporous Carbon Nanofibers
Anode.
AB - A novel Li-ion capacitor based on an activated carbon cathode and a well
dispersed ultrafine TiO2 nanoparticles embedded in mesoporous carbon nanofibers
(TiO2@PCNFs) anode was reported. A series of TiO2@PCNFs anode materials were
prepared via a scalable electrospinning method followed by carbonization and a
postetching method. The size of TiO2 nanoparticles and the mesoporous structure
of the TiO2@PCNFs were tuned by varying amounts of tetraethyl orthosilicate
(TEOS) to increase the energy density and power density of the LIC significantly.
Such a subtle designed LIC displayed a high energy density of 67.4 Wh kg-1 at a
power density of 75 W kg-1. Meanwhile, even when the power density was increased
to 5 kW kg-1, the energy density can still maintain 27.5 Wh kg-1. Moreover, the
LIC displayed a high capacitance retention of 80.5% after 10000 cycles at 10 A g
1. The outstanding electrochemical performance can be contributed to the
synergistic effect of the well-dispersed ultrafine TiO2 nanoparticles, the
abundant mesoporous structure, and the conductive carbon networks.
PMID- 28497690
TI - Novel Electrochemiluminescence-Sensing Platform for the Precise Analysis of
Multiple Latent Tuberculosis Infection Markers.
AB - Latent tuberculosis infection (LTBI) is one of the major contributing factors for
the high incidence of tuberculosis, and the low contents of LTBI markers in human
serum present a great challenge for the diagnosis of LTBI. Here, we reported a
novel electrochemiluminescence (ECL)-sensing platform for the precise analysis of
multiple LTBI markers, interferon-gamma (IFN-gamma) and interleukin (IL)-2. In
this approach, self-prepared carbon quantum dots (CQDs) and luminol were
integrated onto gold nanoparticles (AuNPs), which were further enriched on the
surface of magnetic bead (MB) to create two solid-phase ECL nanoprobes
(MB@Au@CQDs and MB@Au@luminol) for improving the detection sensitivity
efficiently. Graphene oxide (GO) and AuNPs were electrodeposited onto a patterned
indium tin oxide (ITO) electrode with two spatially resolved areas in sequence to
form two sensitive and stable sensing areas. IFN-gamma-antibody (Ab)1 and IL-2
Ab1 were separately immobilized on the two sensing areas to capture the
corresponding LTBI markers, which were further recognized by IFN-gamma-Ab2 and IL
2-Ab2 labeled as MB@Au@CQDs and MB@Au@luminol. The ECL intensity depended
linearly on the content of IFN-gamma and IL-2 in the range of 0.01-1000 pg mL-1,
with a low detection limit of 10 fg mL-1. The proposed ECL-sensing platform is
simple, sensitive, accurate, reliable, and specific to the detection of rare IFN
gamma and IL-2 in human serum and provides a valuable protocol for facilitating
fast and precise diagnosis of LTBI.
PMID- 28497692
TI - Molecular Iodine-Mediated alpha-C-H Oxidation of Pyrrolidines to N,O-Acetals:
Synthesis of (+/-)-Preussin by Late-Stage 2,5-Difunctionalizations of
Pyrrolidine.
AB - We previously reported an iterative synthesis of unsymmetrical 2,5-disubstituted
pyrrolidines from pyrrolidine by two rounds of redox-triggered alpha-C-H
functionalization. Although this approach can be used to introduce substituents
at the 2- and 5-positions, it is lengthy because the redox auxiliary must be
removed and then reinstalled. Therefore, we sought to develop a method to oxidize
2-functionalized pyrrolidine to cyclic N,O-acetal which could then react with a
nucleophile for introduction of the 5-substituent. In this work, we found that
molecular iodine can mediate the preferential oxidation of secondary over
tertiary alpha-C-H bonds of alpha-substituted pyrrolidines to form cyclic N,O
acetals, improving the step economy of our previously reported method. With this
strategy, (+/-)-preussin and its C(3) epimer were synthesized from (+/-)
pyrrolidin-3-ol.
PMID- 28497691
TI - Fine-Tuned Photoactive and Interconnection Layers for Achieving over 13%
Efficiency in a Fullerene-Free Tandem Organic Solar Cell.
AB - Fabricating organic solar cells (OSCs) with a tandem structure has been
considered an effective method to overcome the limited light absorption spectra
of organic photovoltaic materials. Currently, the most efficient tandem OSCs are
fabricated by adopting fullerene derivatives as acceptors. In this work, we
designed a new non-fullerene acceptor with an optical band gap (Egopt) of 1.68 eV
for the front subcells and optimized the phase-separation morphology of a
fullerene-free active layer with an Egopt of 1.36 eV to fabricate the rear
subcell. The two subcells show a low energy loss and high external quantum
efficiency, and their photoresponse spectra are complementary. In addition, an
interconnection layer (ICL) composed of ZnO and a pH-neutral self-doped
conductive polymer, PCP-Na, with high light transmittance in the near-IR range
was developed. From the highly optimized subcells and ICL, solution-processed
fullerene-free tandem OSCs with an average power conversion efficiency (PCE)
greater than 13% were obtained.
PMID- 28497687
TI - Eukaryotic Translesion DNA Synthesis on the Leading and Lagging Strands: Unique
Detours around the Same Obstacle.
AB - During S-phase, minor DNA damage may be overcome by DNA damage tolerance (DDT)
pathways that bypass such obstacles, postponing repair of the offending damage to
complete the cell cycle and maintain cell survival. In translesion DNA synthesis
(TLS), specialized DNA polymerases replicate the damaged DNA, allowing stringent
DNA synthesis by a replicative polymerase to resume beyond the offending damage.
Dysregulation of this DDT pathway in human cells leads to increased mutation
rates that may contribute to the onset of cancer. Furthermore, TLS affords human
cancer cells the ability to counteract chemotherapeutic agents that elicit cell
death by damaging DNA in actively replicating cells. Currently, it is unclear how
this critical pathway unfolds, in particular, where and when TLS occurs on each
template strand. Given the semidiscontinuous nature of DNA replication, it is
likely that TLS on the leading and lagging strand templates is unique for each
strand. Since the discovery of DDT in the late 1960s, most studies on TLS in
eukaryotes have focused on DNA lesions resulting from ultraviolet (UV) radiation
exposure. In this review, we revisit these and other related studies to dissect
the step-by-step intricacies of this complex process, provide our current
understanding of TLS on leading and lagging strand templates, and propose
testable hypotheses to gain further insights.
PMID- 28497693
TI - Palladium-Mediated Approach to Coumarin-Functionalized Amino Acids.
AB - Incorporation of the fluorogenic l-(7-hydroxycoumarin-4-yl)ethylglycine into
proteins is a valuable biological tool. Coumarins are typically accessed via the
Pechmann reaction, which requires acidic conditions and lacks substrate
flexibility. A Pd-mediated coupling is described between o-methoxyboronic acids
and a glutamic acid derived (Z)-vinyl triflate, forming latent coumarins. Global
deprotection with BBr3 forms the coumarin scaffold in a single step. This mild
and scalable route yielded five analogues, including a probe suitable for use at
lower pH.
PMID- 28497694
TI - Stapled RGD Peptide Enables Glioma-Targeted Drug Delivery by Overcoming Multiple
Barriers.
AB - Malignant glioma, the most frequent and aggressive central nervous system (CNS)
tumor, severely threatens human health. One reason for its poor prognosis and
short survival is the presence of the blood-brain barrier (BBB) and blood-brain
tumor barrier (BBTB), which restrict the penetration of therapeutics into the
brain at different stages of glioma. Herein, inspired by the peptide stapling
technique, we designed a cyclic RGD ligand via an all-hydrocarbon staple (stapled
RGD, sRGD) to facilitate BBB penetration while retaining the capacity of BBTB
penetration and targeting ability to glioma cells. As expected, sRGD-modified
micelles were able to penetrate the in vitro BBB model while retaining the glioma
targeted capability. The results of the in vivo imaging studies further revealed
that this nanocarrier could not only efficiently transverse the intact BBB of
normal mice, but also could specifically target glioma cells of intracranial
glioma-bearing nude mice. Furthermore, Paclitaxel-loaded sRGD-modified micelles
exhibited improved antiglioma efficacy in vitro and significantly prolonged
survival time of glioma-bearing nude mice. Overall, this sRGD peptide showed
potency for glioma-targeted drug delivery by overcoming multiple barriers.
PMID- 28497695
TI - Origin of in Situ Domain Formation of Heavily Nb-Doped Pb(Zr,Ti)O3 Thin Films
Sputtered on Ir/TiW/SiO2/Si Substrates for Mobile Sensor Applications.
AB - High-quality piezoelectric thin films have recently been in demand for mobile
sensor applications. An investigation was conducted to understand the
improvements in the piezoelectric and imprint characteristics of heavily Nb-doped
lead zirconate titanate thin films with an extensive range of Nb content (up to
14 mol %) beyond the typical solid solubility limit of Nb. The positive effects
produced by the unusual doping of Nb were realized by utilizing an in situ
sputtering process that did not require a subsequent annealing and poling
procedure. An enhanced piezoelectric coefficient, -e31, of -12.87 C/m2 and a
stronger shift in the coercive field, Ec,shift, of ~20 kV/cm, which are ideally
useful for mobile sensor applications, were obtained for the 12 mol % Nb-doped
films deposited on nonconventional buffer electrodes of Ir/TiW. The reduced
oxygen vacancy concentration and preferred domain orientation with a stronger
piezoresponse induced by the Nb donor doping contributed to the enhancement of
the piezoelectric properties. Potential defect dipoles aligned by a residual
stress gradient along columnar structures seemed to induce an internal electric
field in the Nb-doped films, leading to the preferred domain orientation, as well
as the strong imprint behavior due to a clamping of domain walls.
PMID- 28497696
TI - Chemical Imaging by Dissolution Analysis: Localized Kinetics of Dissolution
Behavior to Provide Two-Dimensional Chemical Mapping and Tomographic Imaging on a
Nanoscale.
AB - A new approach to achieving chemical mapping on a nanoscale is described that can
provide 2D and tomographic images of surface and near-surface structure. The
method comprises dissolving material from the surface of the sample by applying a
series of aliquots of solvent, then analyzing their contents after removing them;
in between exposures, the surface is imaged with atomic force microscopy. This
technique relies on being able to compensate for any drift between images by use
of software. It was applied to a blend of two polymers, PMMA and PS. The
analytical data identified the material that was dissolved, and the topography
images enabled the location of the various materials to be determined by
analyzing local dissolution kinetics. The prospects for generalizing the approach
are discussed.
PMID- 28497697
TI - Synthetic Protein Scaffolds for Biosynthetic Pathway Colocalization on Lipid
Droplet Membranes.
AB - Eukaryotic biochemistry is organized throughout the cell in and on membrane-bound
organelles. When engineering metabolic pathways this organization is often lost,
resulting in flux imbalance and a loss of kinetic advantages from enzyme
colocalization and substrate channeling. Here, we develop a protein-based
scaffold for colocalizing multienzyme pathways on the membranes of intracellular
lipid droplets. Scaffolds based on the plant lipid droplet protein oleosin and
cohesin-dockerin interaction pairs recruited upstream enzymes in yeast ester
biosynthesis to the native localization of the terminal reaction step, alcohol-O
acetyltransferase (Atf1). The native localization is necessary for high activity
and pathway assembly in close proximity to Atf1 increased pathway flux. Screening
a library of scaffold variants further showed that pathway structure can alter
catalysis and revealed an optimized scaffold and pathway expression levels that
produced ethyl acetate at a rate nearly 2-fold greater than unstructured
pathways. This strategy should prove useful in spatially organizing other
metabolic pathways with key lipid droplet-localized and membrane-bound reaction
steps.
PMID- 28497698
TI - Orthogonal Chemical Modification of Template-Synthesized Nanostructures with DNA.
AB - Very few chemical strategies for the selective functionalization of
nanostructures have been developed despite their potential for controlling high
order assembly processes. We report a novel approach for the selective chemical
functionalization and localized assembly of one-dimensional nanostructures
(rods), based upon the systematic activation (DNA functionalization) and
passivation (self-assembled monolayers) of specific surface sites through the use
of orthogonal chemical reactions on electrochemically grown metal nanorod arrays
in porous anodic aluminum oxide templates. The ability to orthogonally
functionalize the ends or the side of a nanorod, as well as the gaps between two
rods, with different DNA strands allows one to synthesize nanostructure
assemblies that would be difficult to realize any other way and that could
ultimately be utilized for making a wide variety of device architectures.
PMID- 28497699
TI - Humanitarian space and well-being: effectiveness of training on a psychosocial
intervention for host community-refugee interaction.
AB - Social and fieldworkers face enormous challenges in assisting millions of Syrian
refugees in Lebanon since the Syrian war in 2011. We sought to assess the
feasibility and acceptability of an adapted version of the SMART-3RP (Stress
Management Relaxation Response Resilience Training) training to address the
emotional and physical burden on the humanitarian field. Data were collected
using the Symptom Checklist-90 (SCL-90), blood pressure, pulse and a brief
qualitative survey at months 0, 3, 6 and 9. We compared mean SCL-90 scores and
physiological measures from these time points and subjected qualitative data to a
thematic analysis. Mean values of all measures decreased from months 0 to 9, with
significance in SCL-90 changes increasing at each visit. Qualitative themes
included decreased stress, increased positivity and problem-solving skills,
interpersonal and personal benefits of mindfulness practice and the need to
continue and expand the programme. Qualitative and quantitative analyses showed a
decrease in stress perception and blood pressure, demonstrating the physiological
benefits of mind body approaches. We highlight the importance of self-care for
humanitarian workers as the basis for the mission's success. We invite additional
research to confirm these findings and their implications for the humanitarian
field.
PMID- 28497700
TI - Instrumental Measurements of Water and the Surrounding Space During a Randomized
Blinded Controlled Trial of Focused Intention.
AB - The main goal of this work was the assessment of measurable interactions induced
by focused intention, frequently used in biofield practices such as Healing Touch
and Reiki. Water, as the main component of the human body, was chosen as a model.
Intention experiments were performed over 4 different days at a scheduled
interval, during which 286 trained biofield practitioners from several countries
were instructed to meditate with the intention to change the molecular
vibrational state of water samples selected by a blinded operator. The
experimental protocol was randomized, blinded, and controlled; the measured
variables included Raman spectra and the pH and electrical conductance of the
water, as well as the magnetic field and UV-VIS (ultraviolet-visible) radiation
near the experimental spot. Although a direct causal relationship cannot be
established, some measurements of the water samples, as well as the magnetic
field and radiation near the experimental spot, were responsive during the
experimental period.
PMID- 28497701
TI - Modified Qigong Breathing Exercise for Reducing the Sense of Hunger on an Empty
Stomach.
AB - BACKGROUND: The aims of this study were to determine whether a modified Qigong
breathing exercise can reduce the sense of hunger and identify possible
mechanisms. METHODS: The results from the test group, which performed the
exercise, are compared with the control group, which performed deep breathing.
Intestinal pressure measurements, stomach pH monitoring, and participant surveys
were used for assessment. RESULTS: Stomach pH was increased by 3 (0.2) and
intestinal pressure was reduced by 12 (0.5) mm Hg in the experimental group and
did not change significantly in the control group. The study provides strong
evidence that the exercise can significantly reduce, or even suppress the sense
of hunger on an empty stomach. CONCLUSION: This breathing exercise provides
comfort in different circumstances, such as lack of regular meals, limited volume
or caloric diet, and even during temporary complete absence of food in
therapeutic fasting.
PMID- 28497703
TI - Association Between Media Doses of the Tips From Former Smokers Campaign and
Cessation Behaviors and Intentions to Quit Among Cigarette Smokers, 2012-2015.
AB - BACKGROUND: Since 2012, the Centers for Disease Control and Prevention (CDC) has
implemented Tips From Former Smokers ( Tips), the first federally funded tobacco
education campaign in the United States. To date, there are no evaluations of its
long-term impact. AIMS: To assess the impact of varied doses of the Tips campaign
from 2012 through 2015 on cessation-related behaviors and intentions among U.S.
smokers. METHOD: We used a national probability-based online survey of cigarette
smokers ( n = 22,189) and recent quitters ( n = 776) to examine associations
between doses of Tips advertising, measured by gross rating points (GRPs), and
intentions to quit smoking in the next 30 days and quit attempts within the past
3 months. A curvilinear (i.e., square root) functional form of GRPs was used to
capture patterns of diminishing effects at higher GRP levels. RESULTS: An
increase of 1,000 quarterly Tips GRPs at the media market level was associated
with increased odds of making a quit attempt in the past 3 months (adjusted odds
ratio = 1.23, p < .001) and increased odds of intending to quit in the next 30
days (adjusted odds ratio = 1.17, p = .030). DISCUSSION: Results suggest that CDC
recommended media buys of 800 to 1,000 GRPs per quarter are sufficient to
generate statistically significant increases in the likelihood of quit attempts
in the past quarter. CONCLUSIONS: The Tips campaign has had a substantial impact
on cessation behaviors among U.S. adult smokers over time. These data support the
continued use of graphic and/or emotional media campaigns that encourage smokers
to quit to further reduce tobacco use in the United States.
PMID- 28497704
TI - What is the right dose of modern medicine?
PMID- 28497705
TI - Circulating biomedical images: Bodies and chromosomes in the post-eugenic era.
AB - This essay presents the early days of human cytogenetics, from the late 1950s
until the mid 1970s, as a historical series of images. I propose a chronology
moving from photographs of bodies to chromosome sets, to be joined by ultrasound
images, which provided a return to bodies, by then focused on the unborn. Images
carried ontological significance and, as I will argue, are principal characters
in the history of human cytogenetics. Inspired by the historiography of heredity
and genetics, studies on visual cultures, the conceptualization of circulation,
and the sociology of pregnancy, I suggest that cytogenetics, through its focus on
pregnancy, pregnant women, and their offspring, found strategic living materials
that stabilized human chromosome studies as a biomedical, post-eugenics practice.
The historicity of each path displays a wide circulation of objects, tools, and
methods that condensed on images that shared in the centuries-old visual
expertise that medicine and botany had manufactured.
PMID- 28497706
TI - Striking ethnic variations in the epidemiology of Chlamydia trachomatis in Haifa
District, Israel, throughout the years 2001-2015.
AB - Our objectives were to examine trends in the incidence of chlamydia over an
extended period and compare the epidemiology of the infection between two
distinct ethnic groups in Israel: Jews and Arabs. We examined the incidence rate
of Chlamydia trachomatis infection among residents of Haifa District, northern
Israel from 2001 to 2015, by reviewing archives of the Department of
Epidemiology, Ministry of Health. Notified cases were stratified by age group,
gender, and ethnic group. The overall incidence rate of Chlamydia was 10.8 cases
per 100,000 population per year. The annual rate increased dramatically from 5.1
per 100,000 population in 2001, to an all-time high of 18.5 cases per 100,000
population in 2015 (P < 0.001), representing an increase of 362.7%. The most
affected age group was 25-34 years of age. The estimated rate among Jewish
inhabitants was ninefold higher than among Arabs. Only 3% recurrent episodes of
Chlamydia were registered. The prevalence of HIV positivity among Chlamydia
infected patients was similar to that of the general population. In conclusion,
Chlamydia in Haifa has been continuously increasing since 2001 and the infection
is much more prevalent among patients of Jewish ethnicity, mainly due to more
hazardous sexual practices in this population.
PMID- 28497707
TI - Multiple physical healthcare needs among outpatients with schizophrenia: findings
from a health examination study.
AB - BACKGROUND: Despite the abundant literature on physical comorbidity, the full
range of the concurrent somatic healthcare needs among individuals with
schizophrenia has rarely been studied. AIMS: This observational study aimed to
assess the distressing somatic symptoms and needs for physical health
interventions in outpatients with schizophrenia, and factors predicting those
needs. METHODS: A structured, comprehensive health examination was carried out,
including a visit to a nurse and a general practitioner on 275 outpatients with
schizophrenia. The required interventions were classified by type of disease.
Logistic regression was used to assess the influence of sociodemographic factors,
lifestyle, functional limitations, factors related to psychiatric disorder, and
healthcare use on the need for interventions. RESULTS: In total, 44.9% of the
patients (mean age 44.9 years) reported somatic symptoms affecting daily life;
87.6% needed specific interventions for a disease or condition, most commonly for
cardiovascular, dermatological, dental, ophthalmological, and gastrointestinal
conditions, and for altered glucose homeostasis. Smoking and obesity predicted
significantly a need of any intervention, but the predictors varied in each
disease category. Strikingly, use of general practitioner services during the
previous year did not reduce the need for interventions. CONCLUSIONS: Health
examinations for outpatients with schizophrenia revealed numerous physical
healthcare needs. The health examinations for patients with schizophrenia should
contain a medical history taking and a physical examination, in addition to basic
measurements and laboratory tests. Prevention and treatment of obesity and
smoking should be given priority in order to diminish somatic comorbidities in
schizophrenia.
PMID- 28497708
TI - Salivary Gland Secretory Carcinoma With High-Grade Transformation, CDKN2A/B Loss,
Distant Metastasis, and Lack of Sustained Response to Crizotinib.
AB - BACKGROUND: Salivary gland secretory carcinoma is usually a low-grade neoplasm.
However, high-grade transformation can occur and has important implications for
clinical outcome. METHODS: A patient presented with an enlarging buccal mass.
Magnetic resonance imaging (MRI) showed a tumor with a biphasic appearance along
the right parotid duct. Local excision and histopathologic examination confirmed
the diagnosis of secretory carcinoma with high-grade transformation. ETV6-NTRK3
translocation and loss of CDKN2A/B were identified. RESULTS: The patient
subsequently presented with cough and dyspnea and was found to have pleural
metastases. Carboplatin and paclitaxel exacerbated the symptoms. Crizotinib
resulted in initial symptomatic and radiographic improvement; however, the
patient soon succumbed to progressive intrathoracic disease. CONCLUSIONS: High
grade salivary gland secretory carcinoma can have a biphasic appearance on MRI.
Diagnosis is confirmed by the histologic appearance and associated ETV6-NTRK3
fusion. Additional molecular genetic events leading to transformation are
unknown; however, loss of CDKN2A/B may have contributed. Treatment with
multimodal chemotherapy was of limited benefit.
PMID- 28497709
TI - Use of proximal side-hole micro-balloon catheter in transcatheter hepatic
arterial chemoembolization.
AB - We report on a 70-year-old man with unresectable multiple hepatocellular
carcinomas who underwent treatment with transcatheter hepatic arterial
chemoembolization. In treating a tumor in segment 1 of the liver, the proximal
side-hole micro-balloon catheter, which has been newly developed, was useful.
PMID- 28497710
TI - The Complex Diagnostic Challenge in Children With Non-Central Nervous System
Cancer and Cerebellar Mutism.
AB - Multiple etiologies should be considered in the differential diagnosis of
immunocompromised patients with non-central nervous system cancer and viral
infections who develop mutism. Acute cerebellitis, caused by infections or by
neurotoxicity resulting from chemotherapy; paraneoplastic cerebellar
degeneration; atypical posterior reversible encephalopathy syndrome; and acute
disseminated encephalomyelitis may all cause mutism in such patients. This
condition warrants prompt recognition and may require treatment with
immunotherapy, as it may be an immune-mediated process. We present 2 patients
with leukemia and viral illness who developed cerebellar mutism in the setting of
acute cerebellitis and responded to immunotherapy, suggesting that the condition
involved a parainfectious immune-mediated response.
PMID- 28497711
TI - Production and covalent immobilisation of the recombinant bacterial carbonic
anhydrase (SspCA) onto magnetic nanoparticles.
AB - Carbonic anhydrases (CAs; EC 4.2.1.1) are metalloenzymes with a pivotal potential
role in the biomimetic CO2 capture process (CCP) because these biocatalysts
catalyse the simple but physiologically crucial reaction of carbon dioxide
hydration to bicarbonate and protons in all life kingdoms. The CAs are among the
fastest known enzymes, with kcat values of up to 106 s-1 for some members of the
superfamily, providing thus advantages when compared with other CCP methods, as
they are specific for CO2. Thermostable CAs might be used in CCP technology
because of their ability to perform catalysis in operatively hard conditions,
typical of the industrial processes. Moreover, the improvement of the enzyme
stability and its reuse are important for lowering the costs. These aspects can
be overcome by immobilising the enzyme on a specific support. We report in this
article that the recombinant thermostable SspCA (alpha-CA) from the thermophilic
bacterium Sulfurihydrogenibium yellowstonense can been heterologously produced by
a high-density fermentation of Escherichia coli cultures, and covalently
immobilised onto the surface of magnetic Fe3O4 nanoparticles (MNP) via
carbodiimide activation reactions. Our results demonstrate that using a benchtop
bioprocess station and strategies for optimising the bacterial growth, it is
possible to produce at low cost a large amount SspCA. Furthermore, the enzyme
stability and storage greatly increased through the immobilisation, as SspCA
bound to MNP could be recovered from the reaction mixture by simply using a
magnet or an electromagnetic field, due to the strong ferromagnetic properties of
Fe3O4.
PMID- 28497712
TI - European General Practice Research Network (EGPRN)Abstracts from the EGPRN
meeting in Leipzig, Germany, 12-16 October 2016. Theme: 'General practice/family
medicine in a changing world'.
PMID- 28497713
TI - Intention stability assessed using residual change scores moderates the intention
behaviour association: a prospective cohort study.
AB - Intention stability is considered to be one of the key pre-requisites for a
strong association between intention and behaviour. It has been claimed, however,
that studies examining the moderating impact of intention stability may be
invalid, as they have relied on statistically inferior methods. Residual change
scores have been suggested as a more appropriate method of measuring change (or
lack thereof) in constructs. The aim of the current study, therefore, is to test
whether intention stability, calculated using residual change scores, moderates
the intention-physical activity behaviour association. A total of 163
participants (124 women, 39 men) completed questionnaires online at three time
points separated by 14 day intervals. The moderating impact of intention
stability was assessed using multiple linear regression followed up using simple
slope analyses to identify the direction of any effect. The interaction of
intention and intention stability was found to significantly improve the overall
model fit. Intentions had a stronger positive association with behaviour when
intentions were more stable than when they were more unstable. However,
sensitivity analyses revealed that the association was not robust and reduced to
non-significant with the removal of potential multivariate outliers. Future
research should use residual change scores as the preferred method of assessing
intention stability.
PMID- 28497714
TI - ECHO Autism: Using Technology and Mentorship to Bridge Gaps, Increase Access to
Care, and Bring Best Practice Autism Care to Primary Care.
PMID- 28497715
TI - Health Maintenance Deficits in a Fully Insured Population of Adolescents With
Chronic Medical Conditions.
AB - The current national monitoring of routine wellness care and vaccine uptake does
not provide data on health maintenance among pediatric populations with chronic
medical conditions. In this case-control study that analyzes wellness visits and
vaccine uptake among adolescents, ages 16 to 18 years, we identified 938 without
(controls) and 74 with (cases) 1 of 12 specific chronic medical conditions. The
PPSV23 (23-valent pneumococcal polysaccharide vaccine) is recommended by the
Advisory Committee on Immunization Practices for these 12 conditions and served
as a measure of uptake for medically indicated vaccines. Our controls were twice
as likely as cases to have a documented well visit in the past year, and there
was a significantly higher proportion of controls than cases vaccinated with Tdap
(tetanus toxoid, reduced diphtheria toxoid, acellular pertussis), MCV-4
(quadrivalent meningococcal conjugate), and HPV (human papillomavirus), all P <
.05. More than 60% of cases failed to receive PPSV23. Adolescents with chronic
medical conditions are at high risk of neglecting routine health maintenance.
PMID- 28497716
TI - Polyglucosan Bodies in Placental Extravillious Trophoblast for the Diagnosis of
Fatal Perinatal Neuromuscular-type Glycogen Storage Disease Type IV.
AB - The fatal infantile neuromuscular type is the most severe form of glycogen
storage disease type IV (GSD IV). We report a case of a 22-day-old female neonate
born at 34 weeks gestation with polyhyramnios, fetal hydrops, and severe
hypotonia. Placental examination revealed numerous periodic acid schiff-positive
diastase-resistant polyglucosan bodies in the cytoplasm of extravillous
trophoblast predominantly in the placental basal plate. Muscle biopsy and autopsy
findings supported a diagnosis of neuromuscular-type glycogen storage disease
type IV with extensive involvement of skeletal muscle, heart, and liver. The
diagnosis was confirmed by molecular genetic testing. We could only find 1 prior
report in the English literature that describes placental pathological changes.
Our findings suggest that placental examination can be a useful adjunct for early
diagnosis, as placentas are often received for pathological examination shortly
after birth and usually before a diagnostic muscle biopsy can be performed.
Pathologists need to be aware of characteristic placental features.
PMID- 28497717
TI - Optic Nerve Calcifications of Unknown Etiology in a 24-week-old Fetus.
PMID- 28497719
TI - Moral Hindsight.
AB - How are judgments in moral dilemmas affected by uncertainty, as opposed to
certainty? We tested the predictions of a consequentialist and deontological
account using a hindsight paradigm. The key result is a hindsight effect in moral
judgment. Participants in foresight, for whom the occurrence of negative side
effects was uncertain, judged actions to be morally more permissible than
participants in hindsight, who knew that negative side effects occurred.
Conversely, when hindsight participants knew that no negative side effects
occurred, they judged actions to be more permissible than participants in
foresight. The second finding was a classical hindsight effect in probability
estimates and a systematic relation between moral judgments and probability
estimates. Importantly, while the hindsight effect in probability estimates was
always present, a corresponding hindsight effect in moral judgments was only
observed among "consequentialist" participants who indicated a cost-benefit trade
off as most important for their moral evaluation.
PMID- 28497720
TI - Neuroscience and Ethics.
AB - A number of people believe that results from neuroscience have the potential to
settle seemingly intractable debates concerning the nature, practice, and
reliability of moral judgments. In particular, Joshua Greene has argued that
evidence from neuroscience can be used to advance the long-standing debate
between consequentialism and deontology. This paper first argues that charitably
interpreted, Greene's neuroscientific evidence can contribute to substantive
ethical discussions by being part of an epistemic debunking argument. It then
argues that taken as an epistemic debunking argument, Greene's argument falls
short in undermining deontological judgments. Lastly, it proposes that accepting
Greene's methodology at face value, neuroimaging results may in fact call into
question the reliability of consequentialist judgments. The upshot is that
Greene's empirical results do not undermine deontology and that Greene's project
points toward a way by which empirical evidence such as neuroscientific evidence
can play a role in normative debates.
PMID- 28497718
TI - The biomechanical effects and perceived comfort of textile-fabricated insoles
during straight line walking.
AB - BACKGROUND: Orthotic insoles that are made of foam material often have less
breathability and thus cause discomfort to the wearer. Given that a sandwich
structure offers better porosity and breathability that would improve comfort,
the impact of custom-made insoles made with three-dimensional spacer fabric is
studied. OBJECTIVES: To examine the biomechanical effects and subjective comfort
of spacer-fabric insoles during walking. STUDY DESIGN: Repeated measures.
METHODS: Plantar pressure and lower limb muscle activity data are collected from
12 subjects. Subjective perceived comfort is measured after five successful
walking trials for each of the three different insoles worn: traditional insoles
made with ethylene vinyl acetate and two types of spacer-fabric insoles. RESULTS:
Compared to the use of traditional insoles, there is a statistically significant
reduction in the peak pressure (>8%) and pressure-time integral (>16%) in the
toes and metatarsal head 1 with the use of the spacer-fabric insoles as the top
layer. Insoles with two layers of spacer fabrics have the highest perceived
comfort ( p < 0.01). However, there is no significant difference in the selected
muscle activity for all three insoles. CONCLUSION: Insoles with different
arrangements of spacer fabrics allow changes in pressure patterns across the
plantar foot and perception of comfort while walking. The findings enhance
current understanding on the use of textile-fabricated materials, which provide
alternative solutions for modifying insoles. Clinical relevance The key features
of spacer fabric offer a viable option for different orthotic insole
applications. The results will greatly contribute toward insole prescription,
potentially enhancing the efficacy of orthotic performance and increasing the
range of insole materials.
PMID- 28497721
TI - Scale Effects in Moral Relevance Assessment.
AB - Research on moral judgment often employs bipolar rating scales to assess whether
the difference between two contrasted options is judged to be morally relevant.
We give an account of how different numbers of response options provided on such
scales (odd vs. even) change the meaning of the test question by communicating
different implicit presuppositions. We demonstrate experimentally that these
changes can qualitatively affect the moral relevance judgments that subjects
express in response to a given judgment problem. Several alternative explanations
in terms of trivial measurement distortion are tested and refuted, and we present
suggestive evidence as to what kind of factors might be prone to scale effects.
The findings underscore that expressed moral judgments are constructed ad hoc and
do not necessarily reflect the content of underlying stable moral commitments. We
discuss implications for theories and methodology in moral psychology and in
judgment and decision-making research more generally.
PMID- 28497722
TI - Moral Severity is Represented as a Domain-General Magnitude.
AB - The severity of moral violations can vary by degree. For instance, although both
are immoral, murder is a more severe violation than lying. Though this point is
well established in Ethics and the law, relatively little research has been
directed at examining how moral severity is represented psychologically. Most
prominent moral psychological theories are aimed at explaining first-order moral
judgments and are silent on second-order metaethical judgments, such as
comparisons of severity. Here, the relative severity of 20 moral violations was
established in a preliminary study. Then, a second group of participants were
asked to decide which of two moral violations was more severe for all possible
combinations of these 20 violations. Participant's response times exhibited two
signatures of domain-general magnitude comparisons: we observed both a distance
effect and a semantic congruity effect. These findings suggest that moral
severity is represented in a similar fashion as other continuous magnitudes.
PMID- 28497723
TI - The Intention-Outcome Asymmetry Effect.
AB - Knowledge of intention and outcome is integral to making judgments of
responsibility, blame, and causality. Yet, little is known about the effect of
conflicting intentions and outcomes on these judgments. In a series of four
experiments, we combine good and bad intentions with positive and negative
outcomes, presenting these through everyday moral scenarios. Our results
demonstrate an asymmetry in responsibility, causality, and blame judgments for
the two incongruent conditions: well-intentioned agents are regarded more morally
and causally responsible for negative outcomes than ill-intentioned agents are
held for positive outcomes. This novel effect of an intention-outcome asymmetry
identifies an unexplored aspect of moral judgment and is partially explained by
extra inferences that participants make about the actions of the moral agent.
PMID- 28497724
TI - Explaining Moral Behavior.
AB - In this review we make a simple theoretical argument which is that for theory
development, computational modeling, and general frameworks for understanding
moral psychology researchers should build on domain-general principles from
reasoning, judgment, and decision-making research. Our approach is radical with
respect to typical models that exist in moral psychology that tend to propose
complex innate moral grammars and even evolutionarily guided moral principles. In
support of our argument we show that by using a simple value-based decision model
we can capture a range of core moral behaviors. Crucially, the argument we
propose is that moral situations per se do not require anything specialized or
different from other situations in which we have to make decisions, inferences,
and judgments in order to figure out how to act.
PMID- 28497725
TI - Factors Guiding Moral Judgment, Reason, Decision, and Action.
PMID- 28497726
TI - EDITORIAL: Neuroprotection Mechanisms and their Potential Applications.
PMID- 28497728
TI - [Give itself the ways to listen to a different voice].
PMID- 28497729
TI - [Optimization and safety assessment of Akkermansia muciniphila for human
administration].
PMID- 28497731
TI - [XBP1 and inflammation in cystic fibrosis alveolar macrophages].
PMID- 28497730
TI - [Development of GnRH neurons in humans: new insights from 3D-imaging of fetal
brains].
PMID- 28497732
TI - [Combined adaptation of roots to flooding and soil nutrients: Role of a MAP3K
protein kinase].
PMID- 28497733
TI - [microRNA and inactivation of the pituitary gonadotrope function].
PMID- 28497734
TI - [Focusing on the functional impact of retinal prothesis].
PMID- 28497735
TI - [Endogenous retroviral sequences in the human genome can play a physiological or
pathological role].
AB - Human endogenous retroviruses (HERV) represent a large part of our genome and the
few elements that have retained a potential of expression still remain "dormant"
in physiological conditions. In some instances, they can be awakened by
environmental factors activating their expression. The best studied conditions of
HERV activation are infections caused by microorganisms such as viruses of the
Herpesvirus family. This activation can thus lead to the expression of pathogenic
proteins such as envelope proteins belonging to the HERV-W and HERV-K families,
respectively involved in Multiple Sclerosis (MS) and amyotrophic lateral
sclerosis (ALS). Endogenous retroviral proteins can also acquire a physiological
function beneficial for humans. This is the case of Syncytin-1 from the HERV-W
family, that is involved in placenta formation.
PMID- 28497736
TI - [Implication of human endogenous retroviruses in schizophrenia and bipolar
disorder].
AB - Schizophrenia and bipolar disorder are neuropsychiatric disorders of unknown
origin. It seems that these two disorders share some common etiopathogenic
mechanisms including genetic, environmental and inflammatory ones. Reactivation
of the human endogenous retrovirus type W (HERV-W) can be a shared element in the
pathophysiology of schizophrenia and bipolar disorder, linked to immuno-genetic
and environment risk factors. We will present studies that have highlighted the
presence of HERV-W in schizophrenic and bipolar disorder patients. We will then
describe a two-hit model which could explain the common pathophysiological
mechanism of affective and non-affective psychosis. Identification of immuno
inflammatory mediated subgroup of schizophrenia and bipolar disorder associated
to HERV-W reactivation might open the way for the development of diagnostic
biomarker and more targeted treatments. These new tools pave the way towards
personalized psychiatry for a better care of patients.
PMID- 28497737
TI - [Phage therapy: a realistic weapon against multidrug resistant bacteria].
AB - The continuous increase in antibiotic resistance among bacteria in infectious
diseases associated with the lack of new antibiotics able to circumvent them are
urging physicians, researchers and politicians to look for others options for
treatments. Among those, phage therapy (use of natural viruses that infect
bacteria, called bacteriophages) is one of the most promising approaches. In this
review, we first focus on the problematic raised by multidrug resistant bacteria
before addressing the main biological characteristics of bacteriophages, as well
as the credibility and the relevance of phage therapy. We then introduce human
applications, their potentials and limits.
PMID- 28497738
TI - [Osteocalcin and glucose metabolism: assessment of human studies].
AB - Osteocalcin, a protein secreted by osteoblasts, is recognized as a biomarker of
bone mineralization. Besides, animal experimental studies have shown that
osteocalcin could play an important role in glucose metabolism. Over the course
of the last decade, this theory has been investigated in several human studies.
Most of the results obtained from these reports support a positive correlation
between total and undercarboxylated osteocalcin and insulin
secretion/sensitivity. Studies also corroborate a reverse association with
glycemic parameters such as fasting glucose and glycated hemoglobin.
Nevertheless, because most of the studies published are observational, it is not
possible to yet confirm a direct cause-effect relationship. Research in the field
will surely contribute to the development of new pharmacological strategies for
the treatment of endocrine diseases.
PMID- 28497739
TI - [Modelling of the blood-brain barrier].
AB - The blood-brain barrier (BBB) is located at the brain microvessel level and
isolates the brain from the whole body, thus restricting molecule and cell
exchanges between cerebral and peripheral compartments. In order to better
decipher and understand the BBB physiology and development, and to investigate
transport mechanism and toxicity of neuropharmaceuticals, several in vitro BBB
models have been developed using animal or human cells, primary or immortalized
cells. The aim of this review is to explain to the reader the major criteria
required for a pertinent in vitro BBB model and to briefly expose the different
models currently available with their characteristics with a special focus on the
static models.
PMID- 28497740
TI - [The PIG-A gene as a new biomarker of mutagenesis: proof of concept and technical
specifications].
AB - Gene mutations are not directly detected by current genotoxicity assays and most
of them need a cell culture step. The whole blood PIG-A assay consists in the
detection of the mutation frequency within the PIG-A sentinel gene by
identification of glycosyl-phosphatidyl-inositol (GPI-) deficient cells. PIG-A
mutated/GPI-deficient cells can be detected by flow cytometry as they no longer
express surface fluorescence for GPI-linked markers. The last researches have
focused on cell enrichment techniques leading to increased throughput and
sensitivity. The results of this new and promising biomarker of mutagenesis,
performed in humans or rodents, are now available within 2 hours after blood
collection.
PMID- 28497741
TI - [Cancer screening fantasies].
AB - The use of circulating tumour DNA to screen for cancer in asymptomatic
individuals is the goal of Grail, initially set up by Illumina. This company is
now raising a large amount of capital to develop this project on a much longer
time scale than initially announced. Although it has access to cutting edge
technology and is led by excellent scientists, the prospect for success in this
application is rather bleak, mainly because of the extreme requirements for
specificity in order to avoid overdiagnosis.
PMID- 28497742
TI - [Relativism, ambiguities and non-alternative scientific facts].
PMID- 28497744
TI - First molecular investigation of Cryptosporidium spp. in young calves in Algeria.
AB - To date, no information is available on the prevalence and genetic identity of
Cryptosporidium spp. in cattle in Algeria. In this study, 17 dairy farms in the
province of Batna, located in the northeast of the country, were visited to
collect 132 fecal samples from young calves (< 8 weeks old). Samples were
examined microscopically using the modified Ziehl-Neelsen acid-fast staining
method, and at least one sample per farm was submitted for molecular analysis.
Amplification of a fragment of the small subunit ribosomal RNA gene was positive
for 24 of the 61 samples (40%), and sequence analysis identified three species,
namely Cryptosporidium bovis (n = 14), C. ryanae (n = 6), and C. parvum (n = 4).
The C. parvum IIaA13G2R1 subtype, an uncommon zoonotic subtype, was identified in
two isolates from a single farm by sequencing a fragment of the GP60 gene. This
is the first report about genotyping and subtyping of Cryptosporidium in calves
in Algeria.
PMID- 28497743
TI - Seroprevalence of Theileria equi and Babesia caballi in horses in Spain.
AB - Equine piroplasmoses are enzootic parasitic diseases distributed worldwide with
high incidence in tropical and subtropical regions. In Spain, there is
insufficient epidemiological data about equine piroplasmoses. The main aim of the
present study was therefore to estimate the prevalence of Theileria equi and
Babesia caballi in five regions and obtain information about the risk factors.
This study was conducted in the central and south-western regions of Spain, using
indirect fluorescence antibody testing (IFAT) in 3,100 sera samples from
apparently healthy horses of different ages, breeds, coat colours, genders and
geographical locations. The overall seroprevalence was 52%, consisting of 44%
seropositive for T. equi and 21% for B. caballi. There was a significant
association between age (p < 0.0001), breed (p < 0.004), geographical location (p
< 0.0001) and the seroprevalence, but neither the coat colour nor the gender was
significantly associated with prevalence. In addition, it was proved that most of
the geographic areas showed a moderate to high prevalence. The statistical kappa
value was used to compare the results obtained by the IFAT and the competitive
enzyme-linked immunosorbent assay (cELISA) utilised to test some samples (n =
108) and showed a higher concordance for T. equi (kappa = 0.68) than for B.
caballi (kappa = 0.22). Consequently, this revealed the importance of developing
an appropriate technique to detect each haemoparasite.
PMID- 28497746
TI - The opioid crisis: the needle and the damage done.
PMID- 28497745
TI - Preventive efficacy of NexGard Spectra(r) against Dipylidium caninum infection in
dogs using a natural flea (Ctenocephalides felis) infestation model.
AB - The efficacy of a monthly oral endectocide product, NexGard Spectra(r) (Merial),
a combination of afoxolaner and milbemycin oxime, was evaluated in a flea
(Ctenocephalides felis) challenge model for the prevention of Dipylidium caninum
tapeworm infection in dogs. The efficacy of treatment with NexGard Spectra(r) was
assessed in 10 dogs following weekly flea infestation with metacestode naturally
infected fleas and compared with that in 10 untreated control dogs. The 100 fleas
deposited weekly on each dog were not removed until Day 35, allowing enough time
for their ingestion. The microscopical analysis of 30 fleas from the flea batches
before each weekly challenge demonstrated that 10-33% of the fleas were infected
by D. caninum cysticercoid larvae. The arithmetic mean flea count recorded was
47.7 for the 10 untreated dogs and 0 for the 10 treated dogs at Day 35. Based on
the daily collection of expelled D. caninum proglottids by dogs during the 70
days of the study, 70% (7/10) of the control dogs and 0% (0/10) of the treated
dogs were infected with D. caninum (p < 0.0031). Through its efficacy against
fleas, NexGard Spectra(r) treatment provided indirect prevention of D. caninum
infestation. No treatment-related adverse events were observed in dogs during
this study.
PMID- 28497747
TI - Stem-cell transplantation for Crohn's disease: same authors, different
conclusions?
PMID- 28497748
TI - The role (if any) of chemotherapy in hepatocellular carcinoma.
PMID- 28497749
TI - PARP inhibitors and chemoradiation for rectal cancer.
PMID- 28497750
TI - Paediatric liver disease: lessons for adult practice.
PMID- 28497751
TI - Early age at diagnosis of hepatocellular carcinoma in sub-Saharan Africa.
PMID- 28497752
TI - Early age at diagnosis of hepatocellular carcinoma in sub-Saharan Africa -
Authors' reply.
PMID- 28497755
TI - Autologous stem-cell transplantation in treatment-refractory Crohn's disease: an
analysis of pooled data from the ASTIC trial.
AB - BACKGROUND: The randomised controlled ASTIC trial showed no benefit of
mobilisation and autologous haematopoietic stem-cell transplantation (HSCT)
compared with mobilisation followed by conventional therapy using a stringent
primary endpoint (steroid-free clinical remission for 3 months with no endoscopic
or radiological evidence of intestinal inflammation) in patients with treatment
refractory Crohn's disease. We now assess HSCT in patients enrolled in the ASTIC
trial using endpoints that are traditional for clinical trials in Crohn's
disease, and identify factors that predict benefit or harm. METHODS: Patients who
underwent mobilisation and were randomly assigned to conventional therapy in the
ASTIC trial were offered HSCT at 1 year and underwent complete assessment for a
further year. We report analyses of the combined cohort of patients who underwent
HSCT at any time during the ASTIC trial programme. The primary outcome for this
analysis was 3-month steroid-free clinical remission at 1 year after HSCT
(Crohn's Disease Activity Index [CDAI] <150). We also examined the degree of
endoscopic healing at 1 year. Multivariate analysis was performed to identify
factors associated with achieving the primary endpoint by using logistic
regression, and factors associated with experiencing a serious adverse event
using Poisson regression. Participants were not masked to treatment, but the
adjudication panel that reviewed radiology and endoscopy was masked to allocation
and visits. All patients who underwent HSCT and had data available at baseline
and 1-year follow-up were included in the primary and safety analysis. This trial
is registered with ClinicalTrials.gov, number NCT00297193. FINDINGS: Between June
28, 2007, and Sept 1, 2011, 45 patients were enrolled in the ASTIC trial from 11
European transplant units. 23 patients were randomly assigned to immediate HSCT,
and 22 patients were assigned to mobilisation followed by conventional care.
After completion of the ASTIC trial, 17 patients from the conventional care group
received HSCT. In the combined cohort, data were available for 40 patients at
baseline and 38 patients at 1 year after HSCT (one patient died, one withdrew).
At 1 year after HSCT, 3-month steroid-free clinical remission was seen in 13
(38%, 95% CI 22-55) of 34 patients with available data for the whole year.
Complete endoscopic healting was noted in 19 (50%, 34-66) of 38 patients. On
multivariate analyses, factors associated with the primary outcome were short
disease duration (odds ratio [OR] 0.64, 95% CI 0.41-0.997 per year; p=0.048) and
low baseline CDAI (0.82, 0.74-0.98 per 10 units; p=0.031). 76 serious adverse
events occurred in 23 of 40 patients with available data. The most common serious
adverse event was infection, most of which were treatment related. Smoking and
perianal disease at baseline were independent factors associated with the number
of serious adverse events (OR 3.07 [95% CI 1.75-5.38; p=0.0001] for smoking and
3.97 [2.17-7.25; p<0.0001] for perianal disease) on multivariate analysis.
INTERPRETATION: When assessed using endpoints traditional for clinical trials of
conventional therapy in Crohn's disease, HSCT resulted in clinical and endoscopic
benefit, although it was associated with a high burden of adverse events. The
prognostic factors identified could allow the therapy to be targeted to patients
most likely to benefit and not experience serious adverse events. FUNDING: Broad
Medical Research Program, National Institute for Health Research Senior
Investigator Award, The University of Nottingham Medical School Dean's Fund, and
The Nottingham University Hospitals NHS Trust Research and Development Fund.
PMID- 28497756
TI - S-1 versus placebo in patients with sorafenib-refractory advanced hepatocellular
carcinoma (S-CUBE): a randomised, double-blind, multicentre, phase 3 trial.
AB - BACKGROUND: Unresectable advanced hepatocellular carcinoma is a heterogeneous
disease, for which sorafenib is the first targeted agent approved for first-line
therapy, and treatment options for patients with sorafenib-refractory advanced
hepatocellular carcinoma are limited. We assessed the efficacy and safety of S-1,
a chemotherapeutic agent based on fluorouracil, in patients with sorafenib
refractory advanced hepatocellular carcinoma. METHODS: We did a randomised,
double-blind, placebo-controlled, phase 3 study done at 57 sites in Japan.
Patients with advanced hepatocellular carcinoma who were ineligible for surgical
or local-regional therapy and judged refractory to sorafenib (ie, had progressed
on sorafenib or had discontinued sorafenib because of adverse events) were
randomly assigned (2:1) to receive oral S-1 (weight-banded 80 mg/m2 [80-120 mg
per day]), or placebo, twice per day for 28 days consecutively, followed by a
minimum 14 day drug-free period. This cycle was repeated until disease
progression or the patient became intolerant to the study treatment. Patients
were stratified by site and presence or absence of extrahepatic metastasis or
vascular invasion. The primary endpoint was overall survival, assessed in the
full analysis set (ie, all patients who were treated with study drug except any
individuals who were found not to have hepatocellular carcinoma or who were found
to have active double cancer). Patients, medical staff, investigators, and the
sponsor were masked to treatment assignment. Blinding was maintained even after
study treatment concluded. This study is registered with JapicCTI, number
JapicCTI-090920, and has been completed. FINDINGS: Between Oct 26, 2009, and Aug
22, 2012, we screened 399 patients. 65 patients were excluded due to not meeting
criteria (n=61), declining to participate (n=3), or other reasons (n=1). 334
patients were randomly assigned to receive either S-1 (n=223) or placebo (n=111).
One patient in the S-1 group did not receive treatment, and was thus excluded
from analyses. At data cutoff, median follow-up was 32.4 months (IQR 24.0-34.7)
in the S-1 group and 32.9 months (23.7-39.5) in the placebo group. Median overall
survival was 11.1 months (95% CI 9.7-13.1) in the S-1 group and 11.2 months (9.2
12.8) in the placebo group (hazard ratio 0.86, 95% CI 0.67-1.10; p=0.220). The
most frequently reported adverse events were skin hyperpigmentation (123 [55%] of
222 patients in the S-1 group vs nine [8%] of 111 patients in the placebo group),
decreased appetite (104 [47%] vs 21 [19%]), fatigue (102 [46%] vs 20 [18%]),
diarrhoea (77 [35%] vs 14 [13%]), and increased blood bilirubin (77 [35%] vs 14
[13%]). Serious adverse events were reported in 90 (41%) of 222 patients in the S
1 group and 24 (22%) of 111 patients in the placebo group. Five treatment-related
deaths were reported in the S-1 group. INTERPRETATION: S-1 did not prolong
overall survival in patients with sorafenib-refractory advanced hepatocellular
carcinoma. Further research is needed to identify subgroups of patients who might
benefit from S-1. FUNDING: Taiho Pharmaceuticals.
PMID- 28497757
TI - Safety and tolerability of veliparib combined with capecitabine plus radiotherapy
in patients with locally advanced rectal cancer: a phase 1b study.
AB - BACKGROUND: Further optimisation of present standard chemoradiation is needed in
patients with locally advanced rectal cancer. Veliparib, an oral poly(ADP-ribose)
polymerase inhibitor, has been shown to enhance the antitumour activity of
chemotherapy and radiotherapy in preclinical models. We aimed to establish the
maximum tolerated dose and establish the recommended phase 2 dose of veliparib
combined with neoadjuvant capecitabine and radiotherapy. METHODS: This phase 1b,
open-label, multicentre, dose-escalation study was done at six hospitals (one in
Australia and five in the USA). Patients were eligible if they were aged 18 years
or more and were newly diagnosed with stage II to III locally advanced,
resectable adenocarcinoma of the rectum with a distal tumour border of less than
12 cm from anal verge. Patients were ineligible if they had received anticancer
therapy or surgery (except colostomy or ileostomy) 28 days or less before the
first dose of study drug, previous pelvic radiotherapy, or previous treatment
with poly (ADP-ribose) polymerase inhibitors. Enrolled patients received
capecitabine (825 mg/m2 orally twice daily) with radiotherapy (50.4 Gy in 1.8 Gy
fractions daily, approximately 5 days consecutively per week for about 5.5
weeks). Veliparib (20-400 mg orally twice daily) was administered daily starting
on day 2 of week 1 and continuing until 2 days after radiotherapy completion.
Patients underwent total mesorectal excision 5-10 weeks after radiotherapy
completion. The primary objectives were to establish the maximum tolerated dose
and recommended phase 2 dose of veliparib plus capecitabine and radiotherapy,
with an exposure-adjusted continual reassessment methodology. Efficacy and safety
analyses were done per protocol. The reported study has completed accrual and all
analyses are final. This trial is registered with ClinicalTrials.gov, number
NCT01589419. FINDINGS: Between June 12, 2012, and Jan 13, 2015, 32 patients
received veliparib (22 in the dose-escalation group; ten in the safety expansion
group); 31 were assessable for efficacy (<400 mg, n=16; 400 mg, n=15). During
dose escalation, grade 2 dose-limiting toxic effects occurred in two patients; no
grade 3-4 dose-limiting toxic effects were noted. Therefore, the maximum
tolerated dose was not reached; the recommended phase 2 dose was selected as 400
mg twice daily. The most common treatment-emergent adverse events in all 32
patients were nausea (17 [53%]), diarrhoea (16 [50%]), and fatigue (16 [50%]).
Grade 3 diarrhoea was noted in three (9%) of 32 patients; no grade 4 events were
reported. Veliparib pharmacokinetics were dose proportional, with no effect on
capecitabine pharmacokinetics. Tumour downstaging after surgery was noted in 22
(71%) of 31 patients; nine (29%) of 31 patients achieved a pathological complete
response. INTERPRETATION: Veliparib plus capecitabine and radiotherapy had an
acceptable safety profile and showed a dose-proportional pharmacokinetic profile
with no effect on the pharmacokinetics of capecitabine. Preliminary antitumour
activity warrants further evaluation. FUNDING: AbbVie Inc.
PMID- 28497759
TI - Long-term challenges and perspectives of pre-adolescent liver disease.
AB - Chronic liver disease is a growing problem that has substantial effects on public
health. Many paediatric liver conditions are precursors of adult chronic liver
disease, cirrhosis, and hepatocellular carcinoma. Clinical management of Wilson's
disease, autoimmune liver disease, and chronic biliary disorders, such as biliary
atresia, which remains the most common paediatric chronic liver disease and
indication for liver transplantation, is similar in children and adults. In the
past 10 or so years, paediatric hepatology has expanded into neighbouring
clinical areas, such as metabolic liver diseases and systemic conditions with
liver involvement. We aim to describe some of these disorders, and outline their
natural history and possible differences between management in adults and
children to stimulate further debate on the optimal transition of care between
paediatric and adult specialists.
PMID- 28497760
TI - The intestinal microbiome and paediatric liver disease.
AB - The intestinal microbiome has been the intense focus of recent study, but how the
microbiota affects connected organs, such as the liver, has not been fully
elucidated. The microbiome regulates intestinal permeability and helps to
metabolise the human diet into small molecules, thus directly affecting liver
health. Several studies have linked intestinal dysbiosis to the severity and
progression of liver diseases, such as non-alcoholic fatty liver disease, non
alcoholic steatohepatitis, primary sclerosing cholangitis, total parenteral
nutrition-associated liver disease, and cystic fibrosis-associated liver disease.
However, there is limited information and interpretation with regard to how the
microbiome could contribute to liver disease in the paediatric population.
Notably, the gut microbiota is distinct at birth and does not establish an adult
profile until the third year of life. Clinical research suggests that paediatric
liver disease differs in both severity and rate of progression compared with
adult forms, suggesting independent mechanisms of pathogenesis. We discuss data
linking the intestinal microbiome to liver disease development and therapeutic
efforts to modify the microbiome in children.
PMID- 28497762
TI - Correction to Lancet Gastroenterol Hepatol 2017; 2: 427-34.
PMID- 28497761
TI - Beyond the Milan criteria for liver transplantation in children with hepatic
tumours.
AB - The Milan criteria were originally defined in the context of adult liver
transplantation for patients with hepatocellular carcinoma and cirrhotic livers.
The aim of the criteria was to select patients with small tumours and no disease
spread who had a good chance of success, thus avoiding futile transplants. This
objective was reached successfully. For the management of selected children with
unresectable hepatoblastoma, an almost opposite strategy was proposed and has
been implemented in the past two decades, in which transplantation is indicated
on the basis of large tumour size and anatomy that precludes the possibility of
safe and radical resection. This approach has also had great success. Although
both strategies are well established for these two different age groups and
diseases, a grey area exists with regard to hepatocellular carcinoma or other
tumour types in children. In this Viewpoint, we aim to review the existing
literature about the indications, selection process, and results of liver
transplantation for liver tumours in children, and discuss evidence that supports
the implementation of either of the two strategies in the context of managing
selected children with liver tumours using transplantation.
PMID- 28497763
TI - [On air ambulance services[Editorial]].
PMID- 28497764
TI - [New year marks a turning point[Editorial]].
PMID- 28497758
TI - Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus
ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with
cirrhosis (ABACUS): a prospective observational study.
AB - BACKGROUND: We ran a compassionate use nationwide programme (ABACUS) to provide
access to ombitasvir, paritaprevir, and ritonavir, with dasabuvir, plus ribavirin
for hepatitis C virus (HCV) genotype 1 infection and ombitasvir, paritaprevir,
and ritonavir, plus ribavirin for HCV genotype 4 infection in patients with
cirrhosis at high risk of decompensation while approval of these regimens was
pending in Italy. METHODS: In this prospective observational study, we collected
data from a compassionate use nationwide programme from March 17, 2014, to May
28, 2015. Patients with HCV genotype 1 infection and cirrhosis at high risk of
decompensation were given coformulated ombitasvir (25 mg), paritaprevir (150 mg),
and ritonavir (100 mg) once daily and dasabuvir (250 mg) twice daily for 12 weeks
(patients with HCV genotype 1b infection) or 24 weeks (patients with HCV genotype
1a infection). Patients with HCV genotype 4 infection were given coformulated
ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once per day
for 24 weeks. All patients were given weight-based ribavirin. The primary
efficacy endpoint was sustained virological response at week 12 after the end of
treatment (SVR12), analysed by intention-to-treat. Univariate and multivariate
logistic regression analyses were used to identify baseline characteristics
associated with SVR12. Adverse events were recorded throughout the study.
FINDINGS: 728 (96%) of 762 patients with cirrhosis who were given ombitasvir,
paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin therapy
for 12 or 24 weeks achieved SVR12. Logistic regression analyses identified that
bilirubin concentrations of less than 2 mg/dL were associated with SVR12 (odds
ratio [OR] 4.76 [95% CI 1.83-12.3]; p=0.001). 166 (23%) of 734 patients included
in safety analyses had an adverse event. 25 (3%) patients discontinued treatment
because of adverse events. Asthenia was the most commonly reported adverse event,
occurring in 36 (5%) patients. INTERPRETATION: Our findings suggest that the
safety and effectiveness of ombitasvir, paritaprevir, and ritonavir, with or
without dasabuvir, plus ribavirin in patients with HCV genotype 1 or 4 infection
and cirrhosis at high risk of decompensation in a real-life setting are similar
to those reported in clinical trials. The concordance with clinical trials
provides reassurance that the reported efficacy of this treatment in clinical
trials will translate to its use in routine clinical practice. FUNDING:
Dipartimento Biomedico di Medicina Interna e Specialistica dell'Universita di
Palermo.
PMID- 28497765
TI - [Acute myocardial infarction among Icelanders forty years old and younger 2005
2009. Comparison with a study carried out 1980-1984].
AB - INTRODUCTION: While acute myocardial infarction (AMI) mostly is a disease of the
elderly it also affects younger individuals, often with serious consequenses. In
1980-1984 a study was carried out on the incidence, risk factors, infarct
location and distribution of atherosclerosis among Icelanders forty years and
younger with AMI. Here we present the results of a similar study carried out for
the five year period 2005-2009. MATERIALS AND METHODS: Medical and autopsy
records of all individuals, forty years and younger, diagnosed with AMI (I21 in
ICD-10) at Landspitali, National University Hospital 2005-2009, or suffering
sudden cardiac death in Iceland during the same period were reviewed. Blood
tests, electrocardiograms, echocardiograms, coronary angiograms and autopsy
results were reviewed with respect to AMI-criteria. Statistical comparisons of
ratios and means were carried out using Chi-square test and T-test, respectively.
RESULTS: 38 individuals 40 years and younger, 32 males and 6 females, fulfilled
the diagnostic criteria of AMI. Calculated incidence for the population at risk
was 10/100.000/year (14/100.000/year in 1980-1984) and the mean age +/-S.D. was
36.7+/-3.9. Three (7.9%) died suddenly before reaching hospital but of the 35
hospitalised patients 30 day mortality was zero, compared to nine (23.7%) pre
hospital deaths and two (6.9%) hospital deaths in 1980-1984. Thus, combined pre
hospital and in-hospital (30 day) mortality was 28.9% and 7.9% in the previous
and recent time periods, respectively (p=0.02). In 2005-2009, 77.1% had a smoking
history and 31.4% were hypertensive compared to 97% and 6.9% in 1980-85 (p=0.026
and p=0.015, respectively). Body mass index (BMI) was higher in the later period,
28.6+/-4,8 kg/m2 compared to 26.1+/-3.6 (mean+/-S.D.; p=0.04) but s-cholesterol
was lower, 5.1+/-1.4 mmol/L compared to 6.3+/-1.16 ( mean+/-S.D.; p<0.01). In
both studies single coronary artery disease was the most common angiographic
pattern and the left anterior descending artery most often involved. CONCLUSION:
Our results show that in two surveys 25 years apart AMI patients 40 years and
younger are most often men. Smoking and family history were the most prominent
risk factors during both periods but hypertension and high BMI were more common
in 2005-2009 than in 1980-1984. Prognosis, as indicated by combined pre-hospital
and in-hospital (30 day) mortality has improved. Key words: Myocardial
infarction, forty and younger, incidence, risk factors, mortality, time trend
Correspondence: Gudmundur Thorgeirsson gudmth@landspitali.is.
PMID- 28497766
TI - [MRI for diagnosis of low back pain: Usability, association with symptoms and
influence on treatment].
AB - BACKGROUND: Non-specific low-back pain is a worldwide problem. More specific
diagnosis could improve prognosis. Magnetic resonance imaging (MRI) became
available in Akureyri Hospital in 2004 but its utilisation in diagnosing low-back
pain has not been investigated. OBJECTIVE: To study the use of MRI in diagnosing
low-back pain, correlation of the MRI outcomes with other clinical findings and
its possible effects on treatment. METHODS: Retrospective, descriptive analysis
of patients' journals. Included were all adult (18 years and older) residents of
Akureyri who underwent low-back MRI in Akureyri Hospital in 2009. RESULTS: During
2009, 159 patients (82 women) underwent low-back MRI, mean age 51 years (18-88).
The most common pathological findings were connected to the lumbar disk. Disk
herniation was diagnosed in 38% of the patients, 77% at the L4-L5 or L5-S1 level.
MRI results correlated poorly with symptoms and clinical findings. Treatment
options for disk herniation were prescription of medications (70%), referrals to
physiotherapy (67%) and orthopaedic surgeons (61%). Nine patients were operated.
Among patients referred to physiotherapy, 49% were first examined with MRI and
thus waited longer for referral than those referred directly to physiotherapy
(p=0.008). One year after the MRI, recovery rate was 51%. Prognosis was better
for patients referred to physiotherapy (p=0.024). CONCLUSIONS: MRI seems to be
used for general diagnosis of low-back pain. Symptoms and MRI results correlate
poorly, emphasizing the need for the doctor's thorough weighing of clinical and
MRI findings when diagnosing low-back pain. Recovery rate of patients with lumbar
disk herniation improves by physiotherapy. The general use of MRI might delay
treatment. Key words: Magnetic resonance imaging, clinical diagnosis, low-back
pain, lumbar disk herniation, treatment, physiotherapy. Correspondence: Gunnar
Svanbergsson gsvanbergs@gmail.com.
PMID- 28497767
TI - [Evaluation of a thyroid nodule].
AB - Thyroid nodules are common and their incidence has increased due to various
factors. Systematic approach to the work-up of thyroid nodules is necessary to
decrease overdiagnosis as well as over treatment. Applying the trifecta of
history, physicial examination and high-resolution ultrasound (HRUS) as well as
fine needle aspiration biopsy (FNAB) with added TSH measurement is important in
the work-up. HRUS is a central part in the diagnostic approach, being able to
risk classify nodules and selecting nodules for FNAB. Systematic analysis of
aspirates is necessary to simplify communication between cytologists and
clinicians. 1Department of Otolaryngology - Head and Neck Surgery, Landspitali,
Fossvogi, 2Department of Medicine, University of Iceland. Key words: thyroid
nodule, thyroid cancer, ultrasound, cytology Correspondence: Geir Tryggvason,
geirt@lsh.is.
PMID- 28497768
TI - Antibacterial effects of antiretrovirals, potential implications for microbiome
studies in HIV.
AB - BACKGROUND: Despite being used by more than 18 million people our understanding
of the extent of the effects of antiretrovirals on the human body and other
organisms remains incomplete. In addition, the direct effect of antiretrovirals
on the gut microbiota of HIV-infected individuals has been largely overlooked in
microbiome studies concerned with HIV-infected individuals. METHODS: Here we
tested 25 antiretrovirals on Bacillus subtilis and Escherichia coli using a broth
microdilution assay to assess whether these drugs have an antibacterial effect.
RESULTS: We found that several widely used antiretroviral drugs have in vitro
antibacterial activity against both gram-positive and gram-negative commensal
bacteria. Efavirenz inhibited the growth of B. subtilis with a minimum inhibitory
concentration (MIC) of 16 ug/ml (in all three replicates), while 2',3'
dideoxyinosine and zidovudine inhibited the growth of E. coli with an MIC of 16
32 ug/ml and 0.016-0.125 ug/ml (respectively). CONCLUSIONS: Given the large and
increasing number of individuals on antiretrovirals, and the lifelong nature of
HIV treatment, this proof-of-concept report could have several potential
implications, including an impact of antiretrovirals on bacterial coinfections,
as well as potentials for drug discovery and repositioning.
PMID- 28497769
TI - Automated EEG artifact elimination by applying machine learning algorithms to ICA
based features.
AB - OBJECTIVE: Biological and non-biological artifacts cause severe problems when
dealing with electroencephalogram (EEG) recordings. Independent component
analysis (ICA) is a widely used method for eliminating various artifacts from
recordings. However, evaluating and classifying the calculated independent
components (IC) as artifact or EEG is not fully automated at present. APPROACH:
In this study, we propose a new approach for automated artifact elimination,
which applies machine learning algorithms to ICA-based features. MAIN RESULTS: We
compared the performance of our classifiers with the visual classification
results given by experts. The best result with an accuracy rate of 95% was
achieved using features obtained by range filtering of the topoplots and IC power
spectra combined with an artificial neural network. SIGNIFICANCE: Compared with
the existing automated solutions, our proposed method is not limited to specific
types of artifacts, electrode configurations, or number of EEG channels. The main
advantages of the proposed method is that it provides an automatic, reliable,
real-time capable, and practical tool, which avoids the need for the time
consuming manual selection of ICs during artifact removal.
PMID- 28497770
TI - Anomalous charge transport in reduced graphene oxide films on a uniaxially
strained elastic substrate.
AB - We investigate temperature-dependent charge transport in reduced graphene oxide
(rGO) films coated on flexible polydimethylsiloxane (PDMS) substrates which are
subject to uniaxial strain. Variable strain, up to 10%, results in an anisotropic
morphology comprising of quasi-periodic linear array of deformations which are
oriented perpendicular to the direction of strain. The anisotropy is reflected in
the charge transport measurements, when conduction in the direction parallel and
perpendicular to the applied strain are compared. Temperature dependence of
resistance is measured for different values of strain in the temperature interval
80-300 K. While the resistance increases significantly upon application of
strain, the temperature-dependent response shows anomalous decrease in resistance
ratio R 80 K/R 300 K upon application of strain. This observation of favorable
conduction processes under strain is further corroborated by reduced activation
energy analysis of the temperature-dependent transport data. These anomalous
transport features can be reconciled based on mutually competing effects of two
processes: (i) thinning of graphene at the sites of periodic deformations, which
tends to enhance the overall resistance by a purely geometrical effect, and (ii)
locally enhanced inter-flake coupling in these same regions which contributes to
improved temperature-dependent conduction.
PMID- 28497771
TI - An isometric muscle force estimation framework based on a high-density surface
EMG array and an NMF algorithm.
AB - OBJECTIVE: To realize accurate muscle force estimation, a novel framework is
proposed in this paper which can extract the input of the prediction model from
the appropriate activation area of the skeletal muscle. APPROACH: Surface
electromyographic (sEMG) signals from the biceps brachii muscle during isometric
elbow flexion were collected with a high-density (HD) electrode grid (128
channels) and the external force at three contraction levels was measured at the
wrist synchronously. The sEMG envelope matrix was factorized into a matrix of
basis vectors with each column representing an activation pattern and a matrix of
time-varying coefficients by a nonnegative matrix factorization (NMF) algorithm.
The activation pattern with the highest activation intensity, which was defined
as the sum of the absolute values of the time-varying coefficient curve, was
considered as the major activation pattern, and its channels with high weighting
factors were selected to extract the input activation signal of a force
estimation model based on the polynomial fitting technique. MAIN RESULTS:
Compared with conventional methods using the whole channels of the grid, the
proposed method could significantly improve the quality of force estimation and
reduce the electrode number. SIGNIFICANCE: The proposed method provides a way to
find proper electrode placement for force estimation, which can be further
employed in muscle heterogeneity analysis, myoelectric prostheses and the control
of exoskeleton devices.
PMID- 28497772
TI - Surface-rough Fe-N/C composite wrapped on carbon nanotubes as efficient
electrocatalyst for oxygen reduction reaction.
AB - Fe-N/C composites are considered one of the most promising non-precious-metal
electrocatalysts for oxygen reduction reaction (ORR). In this paper, we fabricate
a novel and efficient carbon nanotube (CNT)-supported Fe-N/C composite catalyst,
via the surface-self-polymerization of polydopamine and then the incorporation
with Fe species on CNTs, followed by the pyrolysis process. The obtained catalyst
demonstrates excellent electrocatalytic performance towards ORR in alkaline
media. The modification of Fe-incorporated nitrogen-rich-carbons (Fe-CNx) on CNTs
lowers the ORR half-wave-potential by ~190 mV, giving this catalyst with an onset
ORR potential of 0.95 V (versus reversible hydrogen electrode (RHE)), a half-wave
potential of 0.82 V (versus RHE), and the limiting current density of 5.39 mA cm
2 in 0.1 M KOH. The performance of the as-prepared catalyst is comparatively
better than the commercially available Pt/C in terms of positive half-wave
potential and larger limiting current, superior durability, and higher tolerance
to the methanol.
PMID- 28497773
TI - Re-evaluation of the steady-state self-quenching constant of quinine bisulphate
from fluorescence measurements in transmission geometry.
AB - In the present work we show that a recent methodology developed by us to acquire
emission spectra and fluorescence quantum yields of highly absorbing samples in
transmission configuration, constitutes a very simple and robust alternative to
determine self-quenching constants, K SQ. We measured the absorption and the
steady-state emission spectra of quinine bisulphate, QBS, solutions ranging
between 1.5 * 10-5 and 1.5 * 10-1 M. From these data, we calculated the expected
emission spectra, affected by re-absorption, for all QBS concentrations. For
higher concentrations, the re-absorption in the excitation/detection direction
reaches values up to 6% of the total emitted intensity. The K SQ of the dye was
re-evaluated from the concentration dependence of the quotients between the
calculated and the experimental integrated emission spectra. The obtained value,
K SQ = 18.4 +/- 0.1 M-1, shows no significant differences with those obtained
from steady-state and average lifetimes by other authors, pointing out the
diffusional nature of the self-quenching phenomenon. The present work helps
clarify some ambiguous aspects concerning the photophysics of QBS, stressing that
re-absorption phenomena must be considered in QBS concentrated solutions for
accuracy measurements.
PMID- 28497774
TI - Evaluation of respiratory- and postural-induced changes on the ballistocardiogram
signal by time warping averaging.
AB - OBJECTIVE: The aim of this work was to evaluate the potential changes in the
ballistocardiogram (BCG) signal induced by different respiratory patterns and
posture, by using the dynamic time warping (DTW) technique. APPROACH: BCG signals
were recorded in a group of 20 healthy volunteers, simultaneously with an
electrocardiogram (ECG). Two recordings, one in a supine (SUP) and one in a
standing (ST) position, including spontaneous breathing, two 1 min apneas (at
full and empty-lungs, respectively) and 30 s of Valsalva, were analyzed. A warped
averaged waveform was computed for each phase, from which amplitude and temporal
parameters were extracted to characterize each condition. MAIN RESULTS:
Variations were found in both amplitude and duration of BCG-derived parameters
among manoeuvres, especially when compared to spontaneous breathing, suggesting a
complex interaction between intra-thoracic pressure changes acting on venous
return, together with the autonomic nervous system modulation on heart rate. The
effect of a hydrostatic pressure gradient elicited by postural conditions was
also evident. SIGNIFICANCE: Posture and respiratory manoeuvres affect the BCG
signal in different ways, probably as a result of changes induced in preload and
afterload. This supports the need to define separate normality ranges for each
posture and/or breathing conditions, as well as the importance of applying
specific manoeuvres to highlight any pathological response in the computed BCG
parameters.
PMID- 28497775
TI - Optical evidence for the spin-state disorder in LaCo1-x Rh x O3.
AB - We have measured the infrared reflectivity of single-crystalline samples of LaCo1
x Rh x O3 (x = 0, 0.05 and 0.10) from 10 to 300 K from 0.05 to 0.15 eV. We find
that the optical phonons of the Co-O stretching mode depend on temperature and
the Rh content. Analysis with three Lorentz oscillators reveals that the spin
state of Co3+ in LaCo1-x Rh x O3 can be understood in terms of a solid solution
of low-spin- and high-spin-state Co3+ ions, and the substituted Rh ion retains
some fraction of the high-spin Co3+ ions down to low temperature.
PMID- 28497776
TI - Using shape to turn off blinking for two-colour multiexciton emission in CdSe/CdS
tetrapods.
AB - Semiconductor nanostructures capable of emitting from two excited states and
thereby of producing two photoluminescence colours are of fundamental and
potential technological significance. In this limited class of nanocrystals,
CdSe/CdS core/arm tetrapods exhibit the unusual trait of two-colour (red and
green) multiexcitonic emission, with green emission from the CdS arms emerging
only at high excitation fluences. Here we show that by synthetic shape-tuning,
both this multi-colour emission process, and blinking and photobleaching
behaviours of single tetrapods can be controlled. Specifically, we find that the
properties of dual emission and single-nanostructure photostability depend on
different structural parameters-arm length and arm diameter, respectively-but
that both properties can be realized in the same nanostructure. Furthermore,
based on results of correlated photoluminescence and transient absorption
measurements, we conclude that hole-trap filling in the arms and partial state
filling in the core are necessary preconditions for the observation of
multiexciton multi-colour emission.
PMID- 28497777
TI - Phase I/II clinical trial to assess safety and efficacy of intratumoral and
subcutaneous injection of HVJ-E in castration-resistant prostate cancer patients.
AB - Inactivated Sendai virus particles (hemagglutinating virus of Japan envelope (HVJ
E)) have a novel antitumor effect: HVJ-E fused to prostate cancer cells via cell
surface receptor causes apoptosis of prostate cancer cells in vitro and in vivo.
HVJ-E also induces antitumor immunity by activating natural killer (NK) cells and
cytotoxic T cells and suppressing regulatory T cells in vivo. We conducted an
open-label, single-arm, phase I/II clinical trial in patients with castration
resistant prostate cancer (CRPC) to determine the safety and efficacy of
intratumoral and subcutaneous injection of HVJ-E. Patients with CRPC who were
docetaxel-resistant or could not receive docetaxel treatment were eligible. HVJ-E
was injected directly into the prostate on day 1 and subcutaneously on days 5, 8
and 12 in two 28-day treatment cycles using a 3+3 dose-escalation design. The
primary end points were to evaluate safety and tolerability of HVJ-E. The
secondary end points were to analyze tumor immunity and antitumor effect. The
study is registered at UMIN Clinical Trials Registry, number UMIN000006142. Seven
patients were enrolled, and six patients received HVJ-E. Grade 2 or 3 adverse
events (Common Terminology Criteria for Adverse Events Ver. 4.0) were urinary
retention and lymphopenia from which the patients recovered spontaneously. No
Grade 4 adverse events were observed. Radiographically, three patients had stable
disease in the low-dose group, and one patient had stable disease and two had
progressive disease in the high-dose group. The prostate-specific antigen (PSA)
declined from 14 to 1.9 ng ml-1 in one patient in the low-dose group after two
cycles of HVJ-E treatment, and the PSA response rate was 16.6%. NK cell activity
was elevated from day 12 to day 28 after HVJ-E administration, whereas serum
interleukin-6, interferon (IFN)-alpha, IFN-beta and IFN-gamma levels were not
affected by HVJ-E treatment. Intratumoral and subcutaneous injections of HVJ-E
are feasible and PSA response was observed in a subgroup of CRPC patients.
PMID- 28497778
TI - PTEN regulates glioblastoma oncogenesis through chromatin-associated complexes of
DAXX and histone H3.3.
AB - Glioblastoma (GBM) is the most lethal type of human brain cancer, where deletions
and mutations in the tumour suppressor gene PTEN (phosphatase and tensin homolog)
are frequent events and are associated with therapeutic resistance. Herein, we
report a novel chromatin-associated function of PTEN in complex with the histone
chaperone DAXX and the histone variant H3.3. We show that PTEN interacts with
DAXX and, in turn PTEN directly regulates oncogene expression by modulating DAXX
H3.3 association on the chromatin, independently of PTEN enzymatic activity.
Furthermore, DAXX inhibition specifically suppresses tumour growth and improves
the survival of orthotopically engrafted mice implanted with human PTEN-deficient
glioma samples, associated with global H3.3 genomic distribution changes leading
to upregulation of tumour suppressor genes and downregulation of oncogenes.
Moreover, DAXX expression anti-correlates with PTEN expression in GBM patient
samples. Since loss of chromosome 10 and PTEN are common events in cancer, this
synthetic growth defect mediated by DAXX suppression represents a therapeutic
opportunity to inhibit tumorigenesis specifically in the context of PTEN
deletion.
PMID- 28497780
TI - Giant five-photon absorption from multidimensional core-shell halide perovskite
colloidal nanocrystals.
AB - Multiphoton absorption processes enable many technologically important
applications, such as in vivo imaging, photodynamic therapy and optical limiting,
and so on. Specifically, higher-order nonlinear absorption such as five-photon
absorption offers significant advantages of greater spatial confinement,
increased penetration depth, reduced autofluorescence, enhanced sensitivity and
improved resolution over lower orders in bioimaging. Organic chromophores and
conventional semiconductor nanocrystals are leaders in two-/three-photon
absorption applications, but face considerable challenges from their small five
photon action cross-sections. Herein, we reveal that the family of halide
perovskite colloidal nanocrystals transcend these constraints with highly
efficient five-photon-excited upconversion fluorescence-unprecedented for
semiconductor nanocrystals. Amazingly, their multidimensional type I (both
conduction and valence band edges of core lie within bandgap of shell) core-shell
(three-dimensional methylammonium lead bromide/two-dimensional octylammonium lead
bromide) perovskite nanocrystals exhibit five-photon action cross-sections that
are at least 9 orders larger than state-of-the-art specially designed organic
molecules. Importantly, this family of halide perovskite nanocrystals may enable
fresh approaches for next-generation multiphoton imaging applications.
PMID- 28497779
TI - L-selectin mechanochemistry restricts neutrophil priming in vivo.
AB - Circulating neutrophils must avoid premature activation to prevent tissue injury.
The leukocyte adhesion receptor L-selectin forms bonds with P-selectin
glycoprotein ligand-1 (PSGL-1) on other leukocytes and with peripheral node
addressin (PNAd) on high endothelial venules. Mechanical forces can strengthen
(catch) or weaken (slip) bonds between biological molecules. How these
mechanochemical processes influence function in vivo is unexplored. Here we show
that mice expressing an L-selectin mutant (N138G) have altered catch bonds and
prolonged bond lifetimes at low forces. Basal lymphocyte homing and neutrophil
recruitment to inflamed sites are normal. However, circulating neutrophils form
unstable aggregates and are unexpectedly primed to respond robustly to
inflammatory mediators. Priming requires signals transduced through L-selectin
N138G after it engages PSGL-1 or PNAd. Priming enhances bacterial clearance but
increases inflammatory injury and enlarges venous thrombi. Thus, L-selectin
mechanochemistry limits premature activation of neutrophils. Our results
highlight the importance of probing how mechanochemistry functions in vivo.
PMID- 28497781
TI - Face classification using electronic synapses.
AB - Conventional hardware platforms consume huge amount of energy for cognitive
learning due to the data movement between the processor and the off-chip memory.
Brain-inspired device technologies using analogue weight storage allow to
complete cognitive tasks more efficiently. Here we present an analogue non
volatile resistive memory (an electronic synapse) with foundry friendly
materials. The device shows bidirectional continuous weight modulation behaviour.
Grey-scale face classification is experimentally demonstrated using an integrated
1024-cell array with parallel online training. The energy consumption within the
analogue synapses for each iteration is 1,000 * (20 *) lower compared to an
implementation using Intel Xeon Phi processor with off-chip memory (with
hypothetical on-chip digital resistive random access memory). The accuracy on
test sets is close to the result using a central processing unit. These
experimental results consolidate the feasibility of analogue synaptic array and
pave the way toward building an energy efficient and large-scale neuromorphic
system.
PMID- 28497782
TI - RAF proteins exert both specific and compensatory functions during tumour
progression of NRAS-driven melanoma.
AB - NRAS and its effector BRAF are frequently mutated in melanoma. Paradoxically,
CRAF but not BRAF was shown to be critical for various RAS-driven cancers,
raising the question of the role of RAF proteins in NRAS-induced melanoma. Here,
using conditional ablation of Raf genes in NRAS-induced mouse melanoma models, we
investigate their contribution in tumour progression, from the onset of benign
tumours to malignant tumour maintenance. We show that BRAF expression is required
for ERK activation and nevi development, demonstrating a critical role in the
early stages of NRAS-driven melanoma. After melanoma formation, single Braf or
Craf ablation is not sufficient to block tumour growth, showing redundant
functions for RAF kinases. Finally, proliferation of resistant cells emerging in
the absence of BRAF and CRAF remains dependent on ARAF-mediated ERK activation.
These results reveal specific and compensatory functions for BRAF and CRAF and
highlight an addiction to RAF signalling in NRAS-driven melanoma.
PMID- 28497784
TI - An integrated parity-time symmetric wavelength-tunable single-mode microring
laser.
AB - Mode control in a laser cavity is critical for a stable single-mode operation of
a ring laser. In this study we propose and experimentally demonstrate an
electrically pumped parity-time (PT)-symmetric microring laser with precise mode
control, to achieve wavelength-tunable single-mode lasing with an improved mode
suppression ratio. The proposed PT-symmetric laser is implemented based on a
photonic integrated circuit consisting of two mutually coupled active microring
resonators. By incorporating multiple semiconductor optical amplifiers in the
microring resonators, the PT-symmetry condition can be achieved by a precise
manipulation of the interplay between the gain and loss in the two microring
resonators, and the incorporation of phase modulators in the microring resonators
enables continuous wavelength tuning. Single-mode lasing at 1,554.148 nm with a
sidemode suppression ratio exceeding 36 dB is demonstrated and the lasing
wavelength is continuously tunable from 1,553.800 to 1,554.020 nm.
PMID- 28497783
TI - BLISS is a versatile and quantitative method for genome-wide profiling of DNA
double-strand breaks.
AB - Precisely measuring the location and frequency of DNA double-strand breaks (DSBs)
along the genome is instrumental to understanding genomic fragility, but current
methods are limited in versatility, sensitivity or practicality. Here we present
Breaks Labeling In Situ and Sequencing (BLISS), featuring the following: (1)
direct labelling of DSBs in fixed cells or tissue sections on a solid surface;
(2) low-input requirement by linear amplification of tagged DSBs by in vitro
transcription; (3) quantification of DSBs through unique molecular identifiers;
and (4) easy scalability and multiplexing. We apply BLISS to profile endogenous
and exogenous DSBs in low-input samples of cancer cells, embryonic stem cells and
liver tissue. We demonstrate the sensitivity of BLISS by assessing the genome
wide off-target activity of two CRISPR-associated RNA-guided endonucleases, Cas9
and Cpf1, observing that Cpf1 has higher specificity than Cas9. Our results
establish BLISS as a versatile, sensitive and efficient method for genome-wide
DSB mapping in many applications.
PMID- 28497785
TI - Charcoal evidence that rising atmospheric oxygen terminated Early Jurassic ocean
anoxia.
AB - The Toarcian Oceanic Anoxic Event (T-OAE) was characterized by a major
disturbance to the global carbon(C)-cycle, and depleted oxygen in Earth's oceans
resulting in marine mass extinction. Numerical models predict that increased
organic carbon burial should drive a rise in atmospheric oxygen (pO2) leading to
termination of an OAE after ~1 Myr. Wildfire is highly responsive to changes in
pO2 implying that fire-activity should vary across OAEs. Here we test this
hypothesis by tracing variations in the abundance of fossil charcoal across the T
OAE. We report a sustained ~800 kyr enhancement of fire-activity beginning ~1 Myr
after the onset of the T-OAE and peaking during its termination. This major
enhancement of fire occurred across the timescale of predicted pO2 variations,
and we argue this was primarily driven by increased pO2. Our study provides the
first fossil-based evidence suggesting that fire-feedbacks to rising pO2 may have
aided in terminating the T-OAE.
PMID- 28497786
TI - Tunable and low-loss correlated plasmons in Mott-like insulating oxides.
AB - Plasmonics has attracted tremendous interests for its ability to confine light
into subwavelength dimensions, creating novel devices with unprecedented
functionalities. New plasmonic materials are actively being searched, especially
those with tunable plasmons and low loss in the visible-ultraviolet range. Such
plasmons commonly occur in metals, but many metals have high plasmonic loss in
the optical range, a main issue in current plasmonic research. Here, we discover
an anomalous form of tunable correlated plasmons in a Mott-like insulating oxide
from the Sr1-xNb1-yO3+delta family. These correlated plasmons have multiple
plasmon frequencies and low loss in the visible-ultraviolet range. Supported by
theoretical calculations, these plasmons arise from the nanometre-spaced
confinement of extra oxygen planes that enhances the unscreened Coulomb
interactions among charges. The correlated plasmons are tunable: they diminish as
extra oxygen plane density or film thickness decreases. Our results open a path
for plasmonics research in previously untapped insulating and strongly-correlated
materials.
PMID- 28497787
TI - Locus-specific histone deacetylation using a synthetic CRISPR-Cas9-based HDAC.
AB - Efforts to manipulate locus-specific histone acetylation to assess their causal
role in gene expression and cellular and behavioural phenotypes have been impeded
by a lack of experimental tools. The Cas9 nuclease has been adapted to target
epigenomic modifications, but a detailed description of the parameters of such
synthetic epigenome remodellers is still lacking. Here we describe a Cas9-based
histone deacetylase (HDAC) and the design principles required to achieve locus
specific histone deacetylation. We assess its range of activity and specificity,
and analyse target gene expression in two different cell types to investigate
cellular context-dependent effects. Our findings demonstrate that the chromatin
environment is an important element to consider when utilizing this synthetic
HDAC.
PMID- 28497788
TI - Real-time atomistic observation of structural phase transformations in individual
hafnia nanorods.
AB - High-temperature phases of hafnium dioxide have exceptionally high dielectric
constants and large bandgaps, but quenching them to room temperature remains a
challenge. Scaling the bulk form to nanocrystals, while successful in stabilizing
the tetragonal phase of isomorphous ZrO2, has produced nanorods with a twinned
version of the room temperature monoclinic phase in HfO2. Here we use in situ
heating in a scanning transmission electron microscope to observe the
transformation of an HfO2 nanorod from monoclinic to tetragonal, with a
transformation temperature suppressed by over 1000 degrees C from bulk. When the
nanorod is annealed, we observe with atomic-scale resolution the transformation
from twinned-monoclinic to tetragonal, starting at a twin boundary and
propagating via coherent transformation dislocation; the nanorod is reduced to
hafnium on cooling. Unlike the bulk displacive transition, nanoscale size
confinement enables us to manipulate the transformation mechanism, and we observe
discrete nucleation events and sigmoidal nucleation and growth kinetics.
PMID- 28497789
TI - Underwater Leidenfrost nanochemistry for creation of size-tailored zinc peroxide
cancer nanotherapeutics.
AB - The dynamic underwater chemistry seen in nature is inspiring for the next
generation of eco-friendly nanochemistry. In this context, green synthesis of
size-tailored nanoparticles in a facile and scalable manner via a dynamic process
is an interesting challenge. Simulating the volcano-induced dynamic chemistry of
the deep ocean, here we demonstrate the Leidenfrost dynamic chemistry occurring
in an underwater overheated confined zone as a new tool for customized creation
of nanoclusters of zinc peroxide. The hydrodynamic nature of the phenomenon
ensures eruption of the nanoclusters towards a much colder region, giving rise to
growth of monodisperse, size-tailored nanoclusters. Such nanoparticles are
investigated in terms of their cytotoxicity on suspension and adherent cells to
prove their applicability as cancer nanotherapeutics. Our research can pave the
way for employment of the dynamic green nanochemistry in facile, scalable
fabrication of size-tailored nanoparticles for biomedical applications.
PMID- 28497790
TI - Quantum vertex model for reversible classical computing.
AB - Mappings of classical computation onto statistical mechanics models have led to
remarkable successes in addressing some complex computational problems. However,
such mappings display thermodynamic phase transitions that may prevent reaching
solution even for easy problems known to be solvable in polynomial time. Here we
map universal reversible classical computations onto a planar vertex model that
exhibits no bulk classical thermodynamic phase transition, independent of the
computational circuit. Within our approach the solution of the computation is
encoded in the ground state of the vertex model and its complexity is reflected
in the dynamics of the relaxation of the system to its ground state. We use
thermal annealing with and without 'learning' to explore typical computational
problems. We also construct a mapping of the vertex model into the Chimera
architecture of the D-Wave machine, initiating an approach to reversible
classical computation based on state-of-the-art implementations of quantum
annealing.
PMID- 28497791
TI - Formation of printable granular and colloidal chains through capillary effects
and dielectrophoresis.
AB - One-dimensional conductive particle assembly holds promise for a variety of
practical applications, in particular for a new generation of electronic devices.
However, synthesis of such chains with programmable shapes outside a liquid
environment has proven difficult. Here we report a route to simply 'pull'
flexible granular and colloidal chains out of a dispersion by combining field
directed assembly and capillary effects. These chains are automatically
stabilized by liquid bridges formed between adjacent particles, without the need
for continuous energy input or special particle functionalization. They can
further be deposited onto any surface and form desired conductive patterns,
potentially applicable to the manufacturing of simple electronic circuits.
Various aspects of our route, including the role of particle size and the
voltages needed, are studied in detail. Looking towards practical applications,
we also present the possibility of two-dimensional writing, rapid solidification
of chains and methods to scale up chain production.
PMID- 28497792
TI - Structural heterogeneity in the intrinsically disordered RNA polymerase II C
terminal domain.
AB - RNA polymerase II contains a repetitive, intrinsically disordered, C-terminal
domain (CTD) composed of heptads of the consensus sequence YSPTSPS. The CTD is
heavily phosphorylated and serves as a scaffold, interacting with factors
involved in transcription initiation, elongation and termination, RNA processing
and chromatin modification. Despite being a nexus of eukaryotic gene regulation,
the structure of the CTD and the structural implications of phosphorylation are
poorly understood. Here we present a biophysical and biochemical interrogation of
the structure of the full length CTD of Drosophila melanogaster, which we
conclude is a compact random coil. Surprisingly, we find that the repetitive CTD
is structurally heterogeneous. Phosphorylation causes increases in radius,
protein accessibility and stiffness, without disrupting local structural
heterogeneity. Additionally, we show the human CTD is also structurally
heterogeneous and able to substitute for the D. melanogaster CTD in supporting
fly development to adulthood. This finding implicates conserved structural
organization, not a precise array of heptad motifs, as important to CTD function.
PMID- 28497793
TI - Image-guided genomics of phenotypically heterogeneous populations reveals
vascular signalling during symbiotic collective cancer invasion.
AB - Phenotypic heterogeneity is widely observed in cancer cell populations. Here, to
probe this heterogeneity, we developed an image-guided genomics technique termed
spatiotemporal genomic and cellular analysis (SaGA) that allows for precise
selection and amplification of living and rare cells. SaGA was used on
collectively invading 3D cancer cell packs to create purified leader and follower
cell lines. The leader cell cultures are phenotypically stable and highly
invasive in contrast to follower cultures, which show phenotypic plasticity over
time and minimally invade in a sheet-like pattern. Genomic and molecular
interrogation reveals an atypical VEGF-based vasculogenesis signalling that
facilitates recruitment of follower cells but not for leader cell motility
itself, which instead utilizes focal adhesion kinase-fibronectin signalling.
While leader cells provide an escape mechanism for followers, follower cells in
turn provide leaders with increased growth and survival. These data support a
symbiotic model of collective invasion where phenotypically distinct cell types
cooperate to promote their escape.
PMID- 28497794
TI - Pore configuration landscape of granular crystallization.
AB - Uncovering grain-scale mechanisms that underlie the disorder-order transition in
assemblies of dissipative, athermal particles is a fundamental problem with
technological relevance. To date, the study of granular crystallization has
mainly focussed on the symmetry of crystalline patterns while their emergence and
growth from irregular clusters of grains remains largely unexplored. Here
crystallization of three-dimensional packings of frictional spheres is studied at
the grain-scale using X-ray tomography and persistent homology. The latter
produces a map of the topological configurations of grains within static
partially crystallized packings. Using numerical simulations, we show that
similar maps are measured dynamically during the melting of a perfect crystal.
This map encodes new information on the formation process of tetrahedral and
octahedral pores, the building blocks of perfect crystals. Four key formation
mechanisms of these pores reproduce the main changes of the map during
crystallization and provide continuous deformation pathways representative of the
crystallization dynamics.
PMID- 28497796
TI - Potent antitumour activity of interleukin-2-Fc fusion proteins requires Fc
mediated depletion of regulatory T-cells.
AB - Interleukin-2 (IL-2) is an established therapeutic agent used for cancer
immunotherapy. Since treatment efficacy is mediated by CD8+ and NK cell activity
at the tumour site, considerable efforts have focused on generating variants that
expand these subsets systemically, as exemplified by IL-2/antibody complexes and
'superkines'. Here we describe a novel determinant of antitumour activity using
fusion proteins consisting of IL-2 and the antibody fragment crystallizable (Fc)
region. Generation of long-lived IL-2-Fc variants in which CD25 binding is
abolished through mutation effectively prevents unwanted activation of CD25+
regulatory T-cells (Tregs) and results in strong expansion of CD25- cytotoxic
subsets. Surprisingly, however, such variants are less effective than wild-type
IL-2-Fc in mediating tumour rejection. Instead, we report that efficacy is
crucially dependent on depletion of Tregs through Fc-mediated immune effector
functions. Our results underpin an unexpected mechanism of action and provide
important guidance for the development of next generation IL-2 therapeutics.
PMID- 28497797
TI - Suppression of cognitive function in hyperthermia; From the viewpoint of
executive and inhibitive cognitive processing.
AB - Climate change has had a widespread impact on humans and natural systems. Heat
stroke is a life-threatening condition in severe environments. The execution or
inhibition of decision making is critical for survival in a hot environment. We
hypothesized that, even with mild heat stress, not only executive processing, but
also inhibitory processing may be impaired, and investigated the effectiveness of
body cooling approaches on these processes using the Go/No-go task with
electroencephalographic event-related potentials. Passive heat stress increased
esophageal temperature (Tes) by 1.30 +/- 0.24 degrees C and decreased cerebral
perfusion and thermal comfort. Mild heat stress reduced the amplitudes of the Go
P300 component (i.e. execution) and No-go-P300 component (i.e. inhibition).
Cerebral perfusion and thermal comfort recovered following face/head cooling,
however, the amplitudes of the Go-P300 and No-go-P300 components remained
reduced. During whole-body cooling, the amplitude of the Go-P300 component
returned to the pre-heat baseline, whereas that of the No-go-P300 component
remained reduced. These results suggest that local cooling of the face and head
does not restore impaired cognitive processing during mild heat stress, and
response inhibition remains impaired despite the return to normothermia.
PMID- 28497795
TI - A simple optogenetic MAPK inhibitor design reveals resonance between
transcription-regulating circuitry and temporally-encoded inputs.
AB - Engineering light-sensitive protein regulators has been a tremendous
multidisciplinary challenge. Optogenetic regulators of MAPKs, central nodes of
cellular regulation, have not previously been described. Here we present
OptoJNKi, a light-regulated JNK inhibitor based on the AsLOV2 light-sensor domain
using the ubiquitous FMN chromophore. OptoJNKi gene-transfer allows optogenetic
applications, whereas protein delivery allows optopharmacology. Development of
OptoJNKi suggests a design principle for other optically regulated inhibitors.
From this, we generate Optop38i, which inhibits p38MAPK in intact illuminated
cells. Neurons are known for interpreting temporally-encoded inputs via interplay
between ion channels, membrane potential and intracellular calcium. However, the
consequences of temporal variation of JNK-regulating trophic inputs, potentially
resulting from synaptic activity and reversible cellular protrusions, on
downstream targets are unknown. Using OptoJNKi, we reveal maximal regulation of c
Jun transactivation can occur at unexpectedly slow periodicities of inhibition
depending on the inhibitor's subcellular location. This provides evidence for
resonance in metazoan JNK-signalling circuits.
PMID- 28497799
TI - Corrigendum: Oxygen impairs oligodendroglial development via oxidative stress and
reduced expression of HIF-1alpha.
PMID- 28497798
TI - Phosphorylation induces sequence-specific conformational switches in the RNA
polymerase II C-terminal domain.
AB - The carboxy-terminal domain (CTD) of the RNA polymerase II (Pol II) large subunit
cycles through phosphorylation states that correlate with progression through the
transcription cycle and regulate nascent mRNA processing. Structural analyses of
yeast and mammalian CTD are hampered by their repetitive sequences. Here we
identify a region of the Drosophila melanogaster CTD that is essential for Pol II
function in vivo and capitalize on natural sequence variations within it to
facilitate structural analysis. Mass spectrometry and NMR spectroscopy reveal
that hyper-Ser5 phosphorylation transforms the local structure of this region via
proline isomerization. The sequence context of this switch tunes the activity of
the phosphatase Ssu72, leading to the preferential de-phosphorylation of specific
heptads. Together, context-dependent conformational switches and biased
dephosphorylation suggest a mechanism for the selective recruitment of cis
proline-specific regulatory factors and region-specific modulation of the CTD
code that may augment gene regulation in developmentally complex organisms.
PMID- 28497800
TI - Reciprocal regulation of the Il9 locus by counteracting activities of
transcription factors IRF1 and IRF4.
AB - The T helper 9 (Th9) cell transcriptional network is formed by an equilibrium of
signals induced by cytokines and antigen presentation. Here we show that, within
this network, two interferon regulatory factors (IRF), IRF1 and IRF4, display
opposing effects on Th9 differentiation. IRF4 dose-dependently promotes, whereas
IRF1 inhibits, IL-9 production. Likewise, IRF1 inhibits IL-9 production by human
Th9 cells. IRF1 counteracts IRF4-driven Il9 promoter activity, and IRF1 and IRF4
have opposing function on activating histone modifications, thus modulating RNA
polymerase II recruitment. IRF1 occupancy correlates with decreased IRF4
abundance, suggesting an IRF1-IRF4-binding competition at the Il9 locus.
Furthermore, IRF1 shapes Th9 cells with an interferon/Th1 gene signature.
Consistently, IRF1 restricts the IL-9-dependent pathogenicity of Th9 cells in a
mouse model of allergic asthma. Thus our study reveals that the molecular ratio
between IRF4 and IRF1 balances Th9 fate, thus providing new possibilities for
manipulation of Th9 differentiation.
PMID- 28497801
TI - PDE4 Inhibition Restores the Balance Between Excitation and Inhibition in VTA
Dopamine Neurons Disrupted by Repeated In Vivo Cocaine Exposure.
AB - Phosphodiesterase type 4 (PDE4) is a family of enzymes that selectively degrade
intracellular cAMP. PDE4 inhibitors have been shown to regulate the rewarding and
reinforcing effects of cocaine, but the underlying mechanisms remain poorly
understood. Here we show that pretreatments with the PDE4 inhibitor rolipram
attenuated cocaine-induced locomotor sensitization in mice. Repeated cocaine
exposure in vivo caused a decrease in inhibitory postsynaptic currents (IPSCs)
and an increase in the AMPAR/NMDAR ratio in ventral tegmental area (VTA) dopamine
neurons in midbrain slices ex vivo. Cocaine exposure disrupted the balance
between excitation and inhibition as shown by an increase in the excitation to
inhibition (E/I) ratio. Rolipram pretreatments in vivo prevented cocaine-induced
reductions in GABAergic inhibition but did not further increase cocaine-induced
potentiation of excitation, leading to the restoration of a balance between
excitation and inhibition and normalization of the E/I ratio. In support of this
idea, we found that repeated cocaine exposure led to an increase in the single
unit action potential firing rate in vivo in VTA dopamine neurons, which was
blocked by rolipram pretreatments. These results suggest that repeated cocaine
exposure in vivo disrupts the balance between excitation and inhibition in VTA
dopamine neurons, while PDE4 inhibition reestablishes the balance between
excitation and inhibition through distinct mechanisms.
PMID- 28497803
TI - Motor neuron disease: Proinflammatory monocytes might contribute to ALS
progression.
PMID- 28497802
TI - Data-Driven Subgroups in Depression Derived from Directed Functional Connectivity
Paths at Rest.
AB - Depressed patients show abnormalities in brain connectivity at rest, including
hyperconnectivity within the default mode network (DMN). However, there is well
known heterogeneity in the clinical presentation of depression that is overlooked
when averaging connectivity data. We used data-driven parsing of neural
connectivity to reveal subgroups among 80 depressed patients completing resting
state fMRI. Directed functional connectivity paths (eg, region A influences
region B) within a depression-relevant network were characterized using Group
Iterative Multiple Model Estimation, a method shown to accurately recover the
direction and presence of connectivity paths in individual participants.
Individuals were clustered using community detection on neural connectivity
estimates. Subgroups were compared on network features and on clinical and
biological/demographic characteristics that influence depression prognosis. Two
subgroups emerged. Subgroup A, containing 71% of the patients, showed a typical
pattern of connectivity across DMN nodes, as previously reported in depressed
patients on average. Subgroup B exhibited an atypical connectivity profile
lacking DMN connectivity, with increased dorsal anterior cingulate-driven
connectivity paths. Subgroup B members had an over-representation of females (87%
of Subgroup B vs 65% of Subgroup A; chi2=3.89, p=0.049), comorbid anxiety
diagnoses (42.9% of Subgroup B vs 17.5% of Subgroup A; chi2=5.34, p=.02), and
highly recurrent depression (63.2% of Subgroup B vs 31.8% of Subgroup A;
chi2=5.38, p=.02). Neural connectivity-based categorization revealed an atypical
pattern of connectivity in a depressed patient subset that would be overlooked in
group comparisons of depressed and healthy participants, and tracks with
clinically relevant phenotypes including anxious depression and episodic
recurrence. Data-driven parsing suggests heterogeneous substrates of depression;
ideally, future work building on these findings will inform personalized
treatment.
PMID- 28497804
TI - Vaccine-based immunotherapeutic approaches to gliomas and beyond.
AB - Astrocytic and oligodendroglial gliomas are intrinsic brain tumours characterized
by infiltrative growth and resistance to classic cancer therapies, which renders
them inevitably lethal. Glioblastoma, the most common type of glioma, also
exhibits neoangiogenesis and profound immunosuppressive properties. Accordingly,
strategies to revert glioma-associated immunosuppression and promote tumour
directed immune responses have been extensively explored in rodent models and in
large clinical trials of tumour immunotherapy. This Review describes vaccination
approaches investigated for the treatment of glioma. Several strategies have
reached phase III clinical trials, including vaccines targeting epidermal growth
factor receptor variant III, and the use of either immunogenic peptides or tumour
lysates to stimulate autologous dendritic cells. Other approaches in early phases
of clinical development employ multipeptide vaccines such as IMA-950,
cytomegalovirus-derived peptides, or tumour-derived peptides such as heat shock
protein-96 peptide complexes and the Arg132His mutant form of isocitrate
dehydrogenase. However, some preclinical trial data suggest that addition of
immunomodulatory reagents such as immune checkpoint inhibitors, transforming
growth factor-beta inhibitors, signal transducer and activator of transcription 3
inhibitors, or modifiers of tryptophan metabolism could augment the therapeutic
activity of vaccination and overcome glioma-associated immunosuppression.
PMID- 28497805
TI - The changing prevalence and incidence of dementia over time - current evidence.
AB - Dementia is an increasing focus for policymakers, civil organizations and
multidisciplinary researchers. The most recent descriptive epidemiological
research into dementia is enabling investigation into how the prevalence and
incidence are changing over time. To establish clear trends, such comparisons
need to be founded on population-based studies that use similar diagnostic and
research methods consistently over time. This narrative Review synthesizes the
findings from 14 studies that investigated trends in dementia prevalence (nine
studies) and incidence (five studies) from Sweden, Spain, the UK, the
Netherlands, France, the USA, Japan and Nigeria. Besides the Japanese study,
these studies indicate stable or declining prevalence and incidence of dementia,
and some provide evidence of sex-specific changes. No single risk or protective
factor has been identified that fully explains the observed trends, but major
societal changes and improvements in living conditions, education and healthcare
might have favourably influenced physical, mental and cognitive health throughout
an individual's life course, and could be responsible for a reduced risk of
dementia in later life. Analytical epidemiological approaches combined with
translational neuroscientific research could provide a unique opportunity to
explore the neuropathology that underlies changing occurrence of dementia in the
general population.
PMID- 28497806
TI - Management of diffuse low-grade gliomas in adults - use of molecular diagnostics.
AB - Diffuse WHO grade II gliomas are histologically and genetically heterogeneous.
The 2016 WHO classification redefines grade II gliomas with respect to
morphological and molecular tumour alterations: grade II oligodendrogliomas are
defined by the presence of whole-arm codeletion in chromosomal arms 1p/19q,
whereas isocitrate dehydrogenase (IDH) mutations define subclasses of
astrocytoma. Although histological grade remains useful, the prognoses of
patients with glioma are more tightly associated with molecular alterations than
with grade, and chromosomal and gene array technologies are becoming increasingly
beneficial in understanding tumour genetic heterogeneity. The indolent nature of
the disease often creates subtle neurological symptoms that can be overlooked or
misunderstood, resulting in delayed diagnosis. Seizures often herald the
diagnosis, especially in patients who have IDH mutations, which are associated
with an increased production of 2-hydroxyglutarate. Treatment paradigms have
shifted, owing to new diagnostic criteria and new clinical trial evidence.
Patients benefit more from chemoradiation than radiation alone, especially those
with tumour IDH1 Arg132His mutations; gross total resection of the tumour,
including tumours with IDH mutations, is associated with prolonged survival.
Initial observation remains appropriate in patients whose rate of disease growth
is not yet completely defined; such patients could include those with completely
resected disease and those with 1p/19q codeleted tumours.
PMID- 28497807
TI - A TRIM insertion in the promoter of Ms2 causes male sterility in wheat.
AB - The male-sterile ms2 mutant has been known for 40 years and has become extremely
important in the commercial production of wheat. However, the gene responsible
for this phenotype has remained unknown. Here we report the map-based cloning of
the Ms2 gene. The Ms2 locus is remarkable in several ways that have implications
in basic biology. Beyond having no functional annotation, barely detectable
transcription in fertile wild-type wheat plants, and accumulated destructive
mutations in Ms2 orthologs, the Ms2 allele in the ms2 mutant has acquired a
terminal-repeat retrotransposon in miniature (TRIM) element in its promoter. This
TRIM element is responsible for the anther-specific Ms2 activation that confers
male sterility. The identification of Ms2 not only unravels the genetic basis of
a historically important breeding trait, but also shows an example of how a TRIM
element insertion near a gene can contribute to genetic novelty and phenotypic
plasticity.
PMID- 28497809
TI - Receptor-like protein ELT1 promotes brassinosteroid signaling through interacting
with and suppressing the endocytosis-mediated degradation of receptor BRI1.
PMID- 28497808
TI - A unique deubiquitinase that deconjugates phosphoribosyl-linked protein
ubiquitination.
AB - Ubiquitination regulates many aspects of host immunity and thus is a common
target for infectious agents. Recent studies have revealed that members of the
SidE effector family of the bacterial pathogen Legionella pneumophila attack
several small GTPases associated with the endoplasmic reticulum by a novel
ubiquitination mechanism that does not require the E1 and E2 enzymes of the host
ubiquitination machinery. In this case, ubiquitin is first activated by ADP
ribosylation at Arg42 by a mono-ADP-ribosyltransferase activity; the intermediate
is then cleaved by a phosphodiesterase activity also residing within SdeA,
concomitant with the attachment of ubiquitin to serine residues of substrate
proteins via a phosphoribosyl linker. Here we demonstrate that the effect of
SidEs is antagonized by SidJ, an effector encoded by a gene situated in the locus
coding for three members of the SidE family (SdeC, SdeB and SdeA). SidJ reverses
ubiquitination of SidEs-modified substrates by cleaving the phosphodiester bond
that links phosphoribosylated ubiquitin to protein substrates. SidJ also displays
classical deubiquitinase activity but does not require catalytic cysteine
residues. Further, these deubiquitinase activities of SidJ are essential for its
role in L. pneumophila infection. Finally, the activity of SidJ is required for
efficiently reducing the abundance of ubiquitinated Rab33b in infected cells
within a few hours after bacterial uptake. Our results establish SidJ as a
ubiquitin-deconjugating enzyme that functions to impose temporal regulation on
the activity of SidE effectors. SidJ may be important in future studies of
signaling cascades mediated by this unique ubiquitination, one that also
potentially regulates cellular processes in eukaryotic cells.
PMID- 28497811
TI - Polar bodies are efficient donors for reconstruction of human embryos for
potential mitochondrial replacement therapy.
PMID- 28497810
TI - Class I histone deacetylases are major histone decrotonylases: evidence for
critical and broad function of histone crotonylation in transcription.
AB - Recent studies on enzymes and reader proteins for histone crotonylation support a
function of histone crotonylation in transcription. However, the enzyme(s)
responsible for histone decrotonylation (HDCR) remains poorly defined. Moreover,
it remains to be determined if histone crotonylation is physiologically
significant and functionally distinct from or redundant to histone acetylation.
Here we present evidence that class I histone deacetylases (HDACs) rather than
sirtuin family deacetylases (SIRTs) are the major histone decrotonylases, and
that histone crotonylation is as dynamic as histone acetylation in mammalian
cells. Notably, we have generated novel HDAC1 and HDAC3 mutants with impaired
HDAC but intact HDCR activity. Using these mutants we demonstrate that selective
HDCR in mammalian cells correlates with a broad transcriptional repression and
diminished promoter association of crotonylation but not acetylation reader
proteins. Furthermore, we show that histone crotonylation is enriched in and
required for self-renewal of mouse embryonic stem cells.
PMID- 28497812
TI - Metastasis: The plastic state.
PMID- 28497814
TI - Liver: FGF21 - the cause of having a 'sweet tooth'?
PMID- 28497813
TI - Warming the mouse to model human diseases.
AB - Humans prefer to live within their thermal comfort or neutral zone, which they
create by making shelters, wearing clothing and, more recently, by regulating
their ambient temperature. These strategies enable humans to maintain a constant
core temperature (a trait that is conserved across all endotherms, including
mammals and birds) with minimal energy expenditure. Although this primordial
drive leads us to seek thermal comfort, we house our experimental animals,
laboratory mice (Mus musculus), under conditions of thermal stress. In this
Review, we discuss how housing mice below their thermoneutral zone limits our
ability to model and study human diseases. Using examples from cardiovascular
physiology, metabolic disorders, infections and tumour immunology, we show that
certain phenotypes observed under conditions of thermal stress disappear when
mice are housed at thermoneutrality, whereas others emerge that are more
consistent with human biology. Thus, we propose that warming the mouse might
enable more predictive modelling of human diseases and therapies.
PMID- 28497815
TI - Reproductive endocrinology: Puberty timing and cancer risk.
PMID- 28497816
TI - Corrigendum to "Eruptive inflamed seborrheic keratoses in the setting of
endometrial adenocarcinoma" [International Journal of Women's Dermatology 1
(2015) 155-156].
AB - [This corrects the article DOI: 10.1016/j.ijwd.2015.07.003.].
PMID- 28497817
TI - Rechargeable and LED-activated ZnGa2O4 : Cr3+ near-infrared persistent
luminescence nanoprobes for background-free biodetection.
AB - Persistent luminescence nanoparticles (PLNPs) have shown great promise in the
field of biomedicine, but are currently limited by the challenge in the synthesis
of high-quality PLNPs with bright persistent luminescence and a long afterglow
time. Herein, we report a facile strategy for the synthesis of monodisperse,
rechargeable and LED-activated ZnGa2O4 : Cr3+ near-infrared (NIR) PLNPs based on
a modified solvothermal liquid-solid-solution method. The as-synthesized PLNPs
are not only flexible for bioconjugation, but could also circumvent the
limitation of the weak persistent luminescence and short afterglow time that most
PLNPs confronted owing to their rechargeable capability. It was unraveled that
both thermal activation and quantum tunneling mechanisms contributed to the
afterglow decay of the PLNPs, and the quantum tunneling was found to dictate the
LED-activated afterglow intensity and lasting time. Furthermore, by utilizing the
superior excitation-free persistent luminescence, we demonstrated for the first
time the application of biotinylated ZnGa2O4 : Cr3+ PLNPs as background-free
luminescent nano-bioprobes for sensitive and specific detection of avidin in a
heterogeneous assay with a limit of detection down to ~150 pM, thus revealing the
great potential of these NIR PLNPs in ultrasensitive biodetection and bioimaging.
PMID- 28497818
TI - New D-D-pi-A triphenylamine-coumarin sensitizers for dye-sensitized solar cells.
AB - Three D-D-pi-A triphenylamine-coumarin sensitizers were designed and synthesized
with a triphenylamine and coumarin double donor and a cyanoacrylic acid acceptor.
Thiophene, bithiophene and phenylthiophene were used as pi-bridges, respectively,
and the effects of different pi-bridges on the photophysical properties and
photovoltaic performance were investigated. With the incorporation of an
additional thiophene unit, the bithiophene pi-bridge contributes to better light
absorption and hence superior JSC compared with the thiophene pi-bridge. Although
the dye with phenylthiophene pi-bridge exhibits an inferior absorption spectrum
to that with the thiophene pi-bridge, it gives a photoelectrical conversion
efficiency of 4.99% and exhibits the best photovoltaic performance of the three
sensitizers, ascribed to its efficient photon-to-current conversion efficiency,
slow charge recombination rate and good electron injection efficiency.
PMID- 28497819
TI - Disorder-induced transition from grain boundary to bulk dominated ionic diffusion
in pyrochlores.
AB - We use molecular dynamics simulations to investigate the role of grain boundaries
(GBs) on ionic diffusion in pyrochlores, as a function of the GB type, chemistry
of the compound, and level of cation disorder. We observe that the presence of
GBs promotes oxygen transport in ordered and low-disordered systems, as the GBs
are found to have a higher concentration of mobile carriers with higher
mobilities than in the bulk. Thus, in ordered samples, the ionic diffusion is 2D,
localized along the grain boundary. When cation disorder is introduced, bulk
carriers begin to contribute to the overall diffusion, while the GB contribution
is only slightly enhanced. In highly disordered samples, the diffusive behavior
at the GBs is bulk-like, and the two contributions (bulk vs. GB) can no longer be
distinguished. There is thus a transition from 2D/GB dominated oxygen diffusivity
to 3D/bulk dominated diffusivity versus disorder in pyrochlores. These results
provide new insights into the possibility of using internal interfaces to enhance
ionic conductivity in nanostructured complex oxides.
PMID- 28497820
TI - Reducibility of ZrO2/Pt3Zr and ZrO2/Pt 2D films compared to bulk zirconia: a
DFT+U study of oxygen removal and H2 adsorption.
AB - Oxide reducibility is an important property that determines the chemical and
physical behavior of the materials under working conditions. Zirconia is a non
reducible oxide that exhibits high resistance to the loss of oxygen and low
reactivity towards hydrogen, two typical processes involved in oxide reduction.
Oxide reducibility can change substantially by nanostructuring (e.g. formation of
nanoparticles). In this study, we investigate theoretically by means of DFT+U
calculations including dispersion interactions the properties of 2D zirconia
films supported on a Pt3Zr alloy and Pt metal surfaces, two systems recently
prepared experimentally. The results show that the supported ZrO2 ultrathin films
behave very differently from the corresponding bulk oxide, with a low formation
energy of oxygen vacancies, and a clear tendency to split the H2 molecule
homolytically with direct reduction of the oxide. The comparison of free-standing
and supported ZrO2 films shows that these peculiar properties are not due to the
formation of a 2D nanostructure, but rather to the presence of the metal support
and of a metal/oxide interface. The results provide evidence for the uncommon
properties of supported 2D oxides.
PMID- 28497821
TI - A cleft type receptor which combines an oxyanion hole with electrostatic
interactions.
AB - A receptor for carboxylic acids which combines an oxyanion-hole structure with
electrostatic forces has been prepared. X-ray diffraction studies have been
carried out to evaluate the geometry of both the free receptor and its associated
species with several carboxylic acids and many different arrangements have been
discovered for the H-bond pattern in the associated species.
PMID- 28497822
TI - B-DNA model systems in non-terran bio-solvents: implications for structure,
stability and replication.
AB - We have computationally analyzed a comprehensive series of Watson-Crick and
mismatched B-DNA base pairs, in the gas phase and in several solvents, including
toluene, chloroform, ammonia, methanol and water, using dispersion-corrected
density functional theory and implicit solvation. Our analyses shed light on how
the molecular-recognition machinery behind life's genetic code depends on the
medium, in order to contribute to our understanding of the possibility or
impossibility for life to exist on exoplanetary bodies. Calculations show how a
common non-terran environment like ammonia, less polar than water, exhibits
stronger hydrogen-bonding affinities, although showing reduced selectivities
towards the correct incorporation of Watson-Crick base pairs into the backbone.
Thus, we prove the viability of DNA replication in a non-terran environment.
PMID- 28497824
TI - Photochemical synthesis of CdS-MIL-125(Ti) with enhanced visible light
photocatalytic performance for the selective oxidation of benzyl alcohol to
benzaldehyde.
AB - In this study, we decorated CdS on the surface of MIL-125(Ti) using a
photochemical method to prepare the CdS-MIL-125(Ti) nanocomposites. The obtained
samples were characterized by a series of techniques such as X-ray diffraction
(XRD), scanning electron microscopy (SEM), photoluminescence (PL) spectra,
electrochemical measurements and UV-Vis diffuse reflectance spectra (DRS). The
results show that the CdS nanoparticles were highly dispersed on surface of MIL
125(Ti). The combination will promote the separation of electron-hole pairs and
increase the dispersity of CdS. The nanocomposites were subsequently used as
photocatalysts in the selective oxidation of benzyl alcohol to benzaldehyde using
the molecular oxygen as the oxidant. The nanocomposites show excellent
performance in the photocatalytic reaction under visible light irradiation. The
conversion of benzyl alcohol to benzaldehyde was about 20.1% with no by-products
observed.
PMID- 28497825
TI - Enhanced photocatalytic hydrogen evolution from in situ formation of few-layered
MoS2/CdS nanosheet-based van der Waals heterostructures.
AB - Here we report for the first time that the H2 bubbles generated by photocatalytic
water splitting are effective in the layer-by-layer exfoliation of MoS2
nanocrystals (NCs) into few layers. The as-obtained few layers can be in situ
assembled with CdS nanosheets (NSs) into van der Waals heterostructures (vdWHs)
of few-layered MoS2/CdS NSs which, in turn, are effective in charge separation
and transfer, leading to enhanced photocatalytic H2 production activity. The few
layered MoS2/CdS vdWHs exhibited a H2 evolution rate of 140 mmol g(CdS)-1 h-1 and
achieved an apparent quantum yield of 66% at 420 nm.
PMID- 28497826
TI - Twisting with a twist: supramolecular helix fluctuations in chiral nematics.
AB - Most theoretical descriptions of lyotropic cholesteric liquid crystals to date
focus on homogeneous systems in which the rod concentration, as opposed to the
rod orientation, is uniform. In this work, we build upon the Onsager-Straley
theory for twisted nematics and study the effect of weak concentration gradients,
generated by some external potential, on the cholesteric twist. We apply our
theory to chiral nematics of nanohelices in which the supramolecular helix sense
is known to spontaneously change sign upon variation of particle concentration,
passing through a so-called compensation point at which the mesoscopic twist
vanishes. We show that the imposed field offers exquisite control of the
handedness and magnitude of the helicoidal director field, even at weak field
strengths. Within the same framework we also quantify the director fluctuation
spectrum and find evidence for a correlation length diverging at the compensation
point.
PMID- 28497823
TI - Natural products modulating the hERG channel: heartaches and hope.
AB - Covering: 1996-December 2016The human Ether-a-go-go Related Gene (hERG) channel
is a voltage-gated potassium channel playing an essential role in the normal
electrical activity in the heart. It is involved in the repolarization and
termination of action potentials in excitable cardiac cells. Mutations in the
hERG gene and hERG channel blockage by small molecules are associated with
increased risk of fatal arrhythmias. Several drugs have been withdrawn from the
market due to hERG channel-related cardiotoxicity. Moreover, as a result of its
notorious ligand promiscuity, this ion channel has emerged as an important
antitarget in early drug discovery and development. Surprisingly, the hERG
channel blocking profile of natural compounds present in frequently consumed
botanicals (i.e. dietary supplements, spices, and herbal medicinal products) is
not routinely assessed. This comprehensive review will address these issues and
provide a critical compilation of hERG channel data for isolated natural products
and extracts over the past two decades (1996-2016). In addition, the review will
provide (i) a solid basis for the molecular understanding of the physiological
functions of the hERG channel, (ii) the translational potential of in vitro/in
vivo results to cardiotoxicity in humans, (iii) approaches for the identification
of hERG channel blockers from natural sources, (iv) future perspectives for
cardiac safety guidelines and their applications within phytopharmaceuticals and
dietary supplements, and (v) novel applications of hERG channel modulation (e.g.
as a drug target).
PMID- 28497827
TI - A dsDNA model optimized for electrokinetic applications.
AB - We present a coarse-grained (CG) model of a charged double-stranded DNA immersed
in an electrolyte solution that can be used for a variety of electrokinetic
applications. The model is based on an earlier rigid and immobile model of Weik
et al. and includes now semi-flexibility and mobility, so that DNA dynamics can
be sufficiently captured to simulate a full nanopore translocation process. To
this end we couple the DNA hydrodynamically via a raspberry approach to a lattice
Boltzmann fluid and parametrize the counterions with a distant dependent
friction. The electrokinetic properties of the CG DNA model inside an infinite
cylinder is fitted against experimental data from Smeets et al. and all-atom
simulation data from Kesselheim et al. The stiffness of our CG DNA is modeled via
a harmonic angle potential fitted against experimental data of Brunet et al.
Finally, the quality of our tuned parameters is tested by measuring the
electrophoretic mobility of our DNA model for various numbers of base pairs and
salt concentrations. Our results compare excellently with the experimental data
sets of Stellwagen et al. and Hoagland et al.
PMID- 28497828
TI - Structural analysis of micrometer-long gold nanowires using a wormlike chain
model and their rheological properties.
AB - The recent growing interest in the applications of gold nanowires (AuNWs) as
flexible materials has raised the fundamental issue of how their mechanical
properties are related to their morphology. In this work, to address this issue,
the systematic synthesis of AuNWs, their structural analysis, and their
rheological investigation were demonstrated. The structural analysis of AuNWs was
performed based on TEM observations and light-scattering experiments. From these
observations, it was found that the length of AuNWs varies from nanometer to
micrometer depending on the reaction time while a constant width of 1.6 nm is
maintained. On the basis of static light-scattering experiments and a wormlike
chain model, the structural parameters of AuNWs during their growth were
successfully obtained. When the contour length of AuNWs reached around 5 MUm, the
AuNW solution showed non-Newtonian behavior and appeared to behave as a gel.
Dynamic viscoelasticity measurements indicated that such viscous behavior is
responsible for entanglement between AuNWs. It is concluded that AuNWs are
analogous with conventional polymers in terms of both their structure and their
rheological behavior.
PMID- 28497829
TI - Organocatalytic synthesis of axially chiral atropisomers.
AB - This Review summarises the recent progress made in the organocatalytic synthesis
of atropisomeric compounds. Methodologies based on dynamic kinetic resolution and
direct access to BINOL-like biaryls are described. A particular emphasis is given
to reaction mechanisms and to the development of strategies to obtain stable
products by increasing the barrier to atropisomer interconversion during the
reaction.
PMID- 28497830
TI - FeCl3 catalysed 7-membered ring formation in a single pot: a new route to indole
fused oxepines/azepines and their cytotoxic activity.
AB - Various oxepine and azepine fused N-heterocyclic derivatives were synthesized
using a new and one-pot reaction of 2,3-dichloro quinoxaline/pyrazine with 2-(1H
indol-2-yl)phenol/aniline in the presence of 25 mol% FeCl3. The reaction
proceeded via C-C bond followed by C-X (X = O or N) bond formation to construct
the central 7-membered ring, affording the desired products in good yields. The
structure assignment was confirmed by the single crystal X-ray analysis of a
synthesized oxepine fused N-heterocycle derivative. Most of the synthesized
compounds were found to be promising when tested for their anti-proliferative
properties against cervical and breast cancer cell lines.
PMID- 28497831
TI - Tuning electric field aligned CNT architectures via chemistry, morphology, and
sonication from micro to macroscopic scale.
AB - Electric-field alignment of carbon nanotubes (CNT) is widely used to produce
composite materials with anisotropic mechanical, electrical, and optical
properties. Nevertheless, consistent results are difficult to achieve, and even
under identical electric field conditions the resulting aligned morphologies can
vary over MUm to cm length scales. In order to improve reproducibility, this
study addresses (1) how solution processing steps (oxidation, sonication) affect
CNT properties, and (2) how CNT chemistry, morphology, and dispersion influence
alignment. Aligned CNT were deposited onto PVDF membranes using a combination of
electric-field alignment and vacuum-filtration. At each step in solution
processing, the CNT chemistry (oxygen content) and morphology (length/diameter)
were characterized and compared to the final aligned morphology. Well-dispersed
CNT with high oxygen content (>8.5%O) yielded uniform membrane coatings and
microscopically aligned CNT, whereas CNT with low oxygen CNT (<2.2%O) produced
aligned bundles visible at a macroscopic level, but microscopically the
individual CNT remained disordered. Based on regression analysis, CNT with larger
mean length and diameter, smaller length and diameter variation, and higher
oxygen content yielded increased electrical anisotropy, and bath sonication was
slightly preferable to probe sonication for initial dispersion.
PMID- 28497832
TI - A unique semiconductor-carbon-metal hybrid structure design as a counter
electrode in dye-sensitized solar cells.
AB - The catalytic activity of counter electrodes (CEs) severely restricts the
photovoltaic conversion efficiency of dye-sensitized solar cells. However,
electrons trapped by bulk defects greatly reduce the catalytic activity of the
CE. In this study, we report a novel In2S3-C-Au hybrid structure designed by
simply decorating Au particles on the surface of carbon-coated hierarchical In2S3
flower-like architectures, which could avoid the abovementioned problems. This
effect can be attributed to the unique contribution of indium sulfide, carbon,
and Au from the hybrid structure, as well as to their synergy. Electrochemical
measurements revealed that the hybrid structure possessed high catalytic activity
and electrochemical stability for the interconversion of the redox couple I3-/I-.
Moreover, this superior performance can be incorporated into the dye-sensitized
solar cells system. We used this hybrid structure as a counter electrode by
casting it on an FTO substrate to form a film, which displayed better
photovoltaic conversion efficiency (8.91%) than the commercial Pt counterpart
(7.67%).
PMID- 28497833
TI - Formic acid catalyzed isomerization of protonated cytosine: a lower barrier
reaction for tautomer production of potential biological importance.
AB - Tautomerism in nucleotide bases is one of the possible mechanisms of DNA
mutation. In spite of numerous studies on the structure and energy of protonated
cytosine tautomers, little information is available on the process of their intra
and intermolecular tautomerizations. The catalytic ability of H2O, HCOOH, and
the HCOOHH2O group to facilitate the tautomerism of the Cyt2t+ to CytN3+ isomer
has been studied. It is shown that the activation free energies of tautomerism in
the gas phase are 161.17, 58.96, 26.06, and 15.69 kJ mol-1, respectively, when
the reaction is carried out in the absence and presence of H2O, HCOOH, or the
HCOOHH2O group. The formation of a doubly hydrogen bonded transition state is
central to lowering the activation free energy and facilitating the
intramolecular hydrogen atom transfer that is required for isomerization. In the
aqueous phase, although the solvent effects of water significantly decrease the
activation free energy of intramolecular tautomerization, the isomerization of
the Cyt2t+ to CytN3+ isomer remains unfavorable, and the HCOOH and HCOOHH2O group
mediated mechanisms are still more favorable. Meanwhile, conventional transition
state theory (CTST) followed by Wigner tunneling correction is then applied to
estimate the rate constants. The rate constant with Wigner tunneling correction
for direct tautomerization is obviously smaller than that of HCOOH-mediated
tautomerization, which is the most plausible mechanism. Finally, another
important finding is that the product complex (CytN3+HCOOH) is in the rapid
tautomeric equilibrium with the reaction complex (Cyt2t+HCOOH) (tau99.9% = 3.84 *
10-12 s), which is implemented by the mechanism of the concerted synchronous
double proton transfer. Its lifetime of the formed CytN3+HCOOH complex (tau =
8.33 * 10-9 s) is almost one order of magnitude larger than the time required for
the replication machinery to forcibly dissociate a base pair into the monomers
during DNA replication (several ns), which is further dissociated into the CytN3+
and HCOOH monomers. The results of the present study demonstrate the feasibility
of acid catalysis for DNA base isomerization reactions that would otherwise be
forbidden.
PMID- 28497834
TI - The effect of carbohydrate structures on the hydrogelation ability and morphology
of self-assembled structures of peptide-carbohydrate conjugates in water.
AB - We describe the construction of peptide-carbohydrate conjugates, namely
glycopeptides, capable of self-assembling in water. We found that disaccharide
structures (epimer or glycosidic-bond geometry) appended to the glycopeptides
have a noticeable effect on the hydrogel formation ability as well as the
morphology of the self-assembled structures. The soft materials consisting of
self-assembled structures with carbohydrates on their surface and various types
of morphologies might be useful as matrices to investigate the function of
carbohydrates in biological events.
PMID- 28497835
TI - Revealing the electrophilicity of N-Ac indoles with FeCl3: a mechanistic study.
AB - Herein, we report a mechanistic exploration of the unusual FeCl3-mediated
hydroarylation of N-Ac indoles. Electron density topology analysis of a crystal,
in situ IR monitoring, Hammett and Taft studies as well as DFT computations
allowed us to determine that activation of acetyl with FeCl3 and of the C2[double
bond, length as m-dash]C3 bond with a proton is involved.
PMID- 28497836
TI - Visible light initiated release of calcium ions through photochemical electron
transfer reactions.
AB - Photolysis of anthraquinone or flavin photosensitizers in the presence of calcium
EDTA complexes results in decomposition of the EDTA complex, releasing free Ca2+.
In the case of the flavin sensitizers, it is shown that millimolar concentrations
of Ca2+ can be released using visible light (>440 nm) and with quantum yields as
high as 0.31. The utility of this system is further demonstrated by in situ
photogelation of an alginate solution.
PMID- 28497837
TI - Frequency of adult type-associated lactase persistence LCT-13910C/T genotypes in
the Czech/Slav and Czech Roma/Gypsy populations.
AB - Lactase non-persistence (leading to primary lactose intolerance) is a genetically
dependent inability to digest lactose in adulthood. As part of the human
adaptation to dairying, the human lactase LCT-13910C/T mutation (which propagates
adult expression of lactase) developed, spread and participated in the adaptation
to dairying. This variant is associated with lactase activity persistence, and
its carriers are able to digest lactose. We compared the frequencies of lactase
13910C/T (rs4988235) genotypes in Czechs/Slavs (N = 288) and Czech Gypsies/Roma
(N = 300), two ethnically different groups where this polymorphism has not yet
been analysed. Allelic frequencies significantly differed between the populations
(p < 0.0001). In Czechs/Slavs, the lactase persistence T allele was present in
76% of the individuals, which is in agreement with frequencies among
geographically neighbouring populations. In the Czech Gypsy/Roma population, only
27% of the adults were carriers of at least one lactase persistence allele,
similar to the Indian population. In agreement with this result, dairy product
consumption was reported by 70.5% of Czechs/Slavs and 39.0% of the Czech
Gypsy/Roma population. Both in the Czech Gypsy/Roma and in the Czech/Slavs
populations, the presence of carriers of the lactase persistence allele was
similar in subjects self-reporting the consumption of unfermented/fresh milk, in
comparison to the others.
PMID- 28497838
TI - Effect of BCHE single nucleotide polymorphisms on lipid metabolism markers in
women.
AB - Butyrylcholinesterase (BChE) activity and polymorphisms in its encoding gene had
previously been associated with metabolic traits of obesity. This study
investigated the association of three single nucleotide polymorphisms (SNPs) in
the BCHE gene: -116G > A (rs1126680), 1615GA (rs1803274), 1914A < G (rs3495),
with obesity and lipid metabolism markers, body mass index (BMI), total
cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density
lipoprotein cholesterol (HDL-C), triglyceride (TG) levels, and BChE enzymatic
activity in obese (BMI>=30/n = 226) and non-obese women (BMI < 25/n = 81). BCHE
SNPs genotyping was obtained by TaqMan allelic discrimination assay and by RFLP
PCR. Plasmatic BChE activity was measured using propionylthiocholine as
substrate. Similar allele frequencies were found in obese and non-obese women for
the three studied SNPs (p > 0.05). The dominant and recessive models were tested,
and different effects were found. The -116A allele showed a dominant effect in
BChE activity reduction in both non-obese and obese women (p = 0.045 and p <
0.001, respectively). The 1914A > G and 1615GA SNPs influenced the TG levels only
in obese women. The 1914G and the 1615A alleles were associated with decreased
plasma levels of TG. Thus, our results suggest that the obesity condition,
characterized by loss of energy homeostasis, is modulated by BCHE polymorphisms.
PMID- 28497839
TI - Evaluation of the association between the TAS1R2 and TAS1R3 variants and food
intake and nutritional status in children.
AB - Taste perception plays a key role in determining individual food preferences and
dietary habits and may influence nutritional status. This study aimed to
investigate the association of TAS1R2 (Ile191Val - rs35874116) and TAS1R3 (-1266
C/T - rs35744813) variants with food intake and nutritional status in children
followed from birth until 7.7 years old. The nutritional status and food intake
data of 312 children were collected at three developmental stages (1, 3.9 and 7.7
years old). DNA was extracted from blood samples and the polymorphisms were
analyzed by real-time polymerase chain reactions (qPCR) using hydrolysis probes
as the detection method. Food intake and nutritional status were compared among
individuals with different single nucleotide polymorphism (SNP) genotypes. At 3.9
years old, children homozygous (Val/Val) for the TAS1R2 Ile191Val polymorphism
ingested less sugar and sugar-dense foods than children who were *Ile carriers.
This finding demonstrated that a genetic variant of the T1R2 taste receptor is
associated with the intake of different amounts of high sugar-content foods in
childhood. This association may provide new perspectives for studying dietary
patterns and nutritional status in childhood.
PMID- 28497840
TI - Risk factors of atrial fibrillation recurrence despite successful radiofrequency
ablation of accessory pathway: At 11 years of follow-up.
AB - BACKGROUND: Previous reports on patients with radiofrequency catheter ablation
(RFCA) of accessory pathway (AP) and atrial fibrillation (AF) include only short
follow-up periods. The aim of this study was to analyze predictors of recurrence
of AF in patients after successful RFCA of APs over long term follow-up periods.
METHODS: Of the 1,007 patients who underwent non-pharmacological treatment of APs
(between the years 1993-2008), data of 100 consecutive patients were
retrospectively analyzed (75 men, mean age 43.6 +/- 14.7), with the longest
period of follow-up (mean 11.3 +/- 3.5 years) after successful RFCA of AP. In
Group 1, there were 72 patients (54 men, mean age 40.66 +/- 13.85 years) without
documented episodes of AF after RFCA of AP. Group 2 consisted of 28 patients (21
men, mean age 50.79 +/- 14.49 years) with AF episodes despite successful
elimination of AP. RESULTS: In univariate analysis, patients from Group 1 were
significantly younger at the time of abla-tion than patients from Group 2 (40.66
+/- 13.85 vs. 50.79 +/- 14.49 years; p = 0.002), had shorter his!tory of AF
episodes (4.11 +/- 4.07 vs. 8.25 +/- 7.50 years; p = 0.024) and had less
frequently documented atrial tachycardia (AT) prior to ablation (3.39 vs. 20.00%
years; p = 0.022). In multivariate analysis, the history of AF in years (p =
0.043), was an independent risk factor for AF recurrences. CONCLUSIONS: Older
patient age, longer history of AF and AT prior to RFCA of APs identified a sub
group of patients who required additional treatment. In the multivariate
analysis, the history of AF in years (p = 0.043) was a risk factor for AF
recurrence.
PMID- 28497841
TI - Effect of fluid resuscitation with balanced solutions on platelets: In vitro
simulation of 20% volume substitution.
AB - BACKGROUND: Fluid resuscitation in massive bleeding may cause coagulation
disorders by dilution of platelets and clotting factors or by the impact on their
function. The aim of this study was to investigate the effects of balanced
crystalloid and colloid solutions on platelets in vitro using complex assessment
of coagulation. METHODS: The study group was comprised of 32 American Society of
Anesthesiologists physical status class I male volunteers, aged 21-35 (29 +/- 4)
years, weighting 59-103 (81.2 +/- 9.8) kg. Whole blood samples were diluted at a
4:1 ratio with the following fluids: balanced crystalloid (Plasmalyte(r)), 6%
hydroxyethyl starch 130/0.4 (Volulyte(r)) and succinylated gelatin
(Geloplasma(r)). Coagulation was as-sessed using standard morphology, rotational
thromboelastometry and aggregometry. RESULTS: Dilution with all fluids caused
statistically significant drop in the number of platelets (p < 0.01) but the
effect did not differ between solutions (p > 0.05 for all). Other platelet
parameters, such as platelet distribution width, mean platelet volume and
platelet-large cell ratio were not affected by the solutions. Hemodilution had no
effect on platelet function (p = 0.1). Decreased platelet component of clot
strength was found for all three fluids (p < 0.05), although the effect for
colloids was more pronounced. CONCLUSIONS: The effect of balanced crystalloids
and colloids on platelet aggregation was insignificant, even after 20% volume
substitution with the resuscitation fluids. (.
PMID- 28497842
TI - Macrophagic enhancement in optical coherence tomography imaging by means of
superparamagnetic iron oxide nanoparticles.
AB - BACKGROUND: The ability of optical coherence tomography (OCT) to visualise
macrophages in vivo in coronary arteries is still controversial. We hypothesise
that imaging of macrophages in OCT could be enhanced by means of
superparamagnetic nanoparticles. METHODS: We compared the optical backscattering
and attenuation of cell pellets containing RAW 264.7 macrophages with those of
macrophagic cell pellets labelled with very small superparamagnetic oxydised
nanoparticles (VSOP) by means of light intensity analysis in OCT. The labelled
macrophages were incubated with VSOP at a concentration of 1 mM Fe, corresponding
to intracellular iron concentrations of 8.8 pg/cell. To study the effect of
intracellular accumulation on the backscattering, VSOP dilutions without cells
were also compared. OCT pullbacks of the PCR tubes containing the cell pellets
were obtained and light intensity analysis was performed on raw OCT images in
polar view, after normalisation by the backscattering of the PCR tube. The
backscattering was estimated by the peak normalised intensity, whilst the
attenuation was estimated by the number of pixels between the peak and the
normalised intensity 1 (peak-to-one). RESULTS: VSOP-loaded macrophages have
higher backscattering than the corresponding unlabelled macrophages (peak
normalised intensity 6.30 vs. 3.15) with also slightly higher attenuation (peak
toone 61 vs. 66 pixels). The backscattering of the nanoparticles in suspension
was negligible in the light intensity analysis. CONCLUSIONS: VSOP increase
significantly the optical backscattering of macrophages in the nearinfrared
region, with minimal increase in signal attenuation. This finding enables the
enhancement of macrophages in conventional OCT imaging with an easily
implementable methodology.
PMID- 28497843
TI - Heart failure: Pilot transcriptomic analysis of cardiac tissue by RNA-sequencing.
AB - BACKGROUND: Despite left ventricular (LV) dysfunction contributing to mortality
in chronic heart failure (HF), the molecular mechanisms of LV failure continues
to remain poorly understood and myocardial biomarkers have yet to be identified.
The aim of this pilot study was to investigate specific transcriptome changes
occurring in cardiac tissues of patients with HF compared to healthy condition
patients to improve diagnosis and possible treatment of affected subjects.
METHODS: Unlike other studies, only dilated cardiomyopathy (DCM) (n = 2) and
restrictive cardiomyopathy (RCM) (n = 2) patients who did not report family
history of the disease were selected with the aim of obtaining a homogeneous
population for the study. The transcriptome of all patients were studied by RNA
sequencing (RNA-Seq) and the read counts were adequately filtered and normalized
using a recently developed user-friendly tool for RNA-Seq data analysis, based on
a new graphical user interface (RNA-SeqGUI). RESULTS: By using this approach in a
pairwise comparison with healthy donors, we were able to identify DCM- and RCM
specific expression signatures for protein-coding genes as well as for long
noncoding RNAs (lncRNAs). Differential expression of 5 genes encoding different
members of the mediator complex was disclosed in this analysis. Interestingly, a
significant alteration was found for genes which had never been associated with
HF until now, and 27 lncRNA/mRNA pairs that were significantly altered in HF
patients. CONCLUSIONS: The present findings revealed specific expression pattern
of both protein-coding and lncRNAs in HF patients, confirming that new LV
myocardial biomarkers could be reliably identified using Next-Generation
Sequencing-based approaches.
PMID- 28497844
TI - Echocardiographic evaluation of right ventricular systolic function: The
traditional and innovative approach.
AB - Estimation of right ventricular (RV) performance still remains technically
challenging due to its anatomical and functional distinctiveness. The current
guidelines for the echocardiographic quantification of RV function recommend
using multiple indices to describe the RV in a thorough and comprehensive manner,
such as RV index of myocardial performance, tricuspid annular plane systolic
excursion, fractional area change, Doppler tissue imaging-derived tricuspid
lateral annular systolic velocity (S'-wave), three-dimensional RV ejection
fraction (3D RVEF), RV longitudinal strain (RVLS)/strain rate by speckle-
tracking echocardiography (STE). Among these, the last one mentioned here is an
innovative and a particularly promising tool that yields more precise information
about complex regional and global RV mechanics. STE was initially designed to
evaluate left ventricular function, but recently it has been introduced to assess
RV performance, which is difficult due to its unique structure and physiology.
Many studies have shown that both free wall and 6-segment RVLS present a stronger
correlation with the RVEF assessed by cardiac magnetic resonance than
conventional parameters and seem to be more sensitive in detecting myocardial
dysfunction at an earlier, subclinical stage.
PMID- 28497845
TI - Comparison of dual antiplatelet therapy versus oral anticoagulation following
transcatheter aortic valve replacement: A retrospective single-center registry
analysis.
AB - BACKGROUND: The choice of optimal antithrombotic regimen after transcatheter
aortic valve replace-ment (TAVR) remains a matter of debate. The objective of
this study was to compare both efficacy and safety outcomes based on the type of
antithrombotic therapy prescribed after TAVR Methods: This is a retrospective
analysis of 514 consecutive patients treated with either dual antiplate!let
therapy (DAPT) (n = 315; 61.3%) or oral anticoagulation (OAC) plus clopidogrel (n
= 199; 38.7%) for a minimum of 3 months after TAVR followed by antiplatelet
monotherapy or OAC only, respectively. Patients had pre-defined clinical and
echocardiographic follow-ups at 30 days, 6 and 12 months. The key efficacy
endpoint was a composite of all-cause death, myocardial infarction, stroke and
valve throm!bosis at 1 year. The key safety endpoint was the occurrence of life
threatening/major bleeding at 1 year. RESULTS: Baseline characteristics did not
differ between both groups, except for a higher incidence of atrial fibrillation
in the OAC group. No significant differences in both efficacy and safety
endpoints were observed at 30 days and 6 months. At 1 year, the key efficacy
endpoint occurred in 21.5% of the DAPT group compared to 19.7% of the OAC group
(p = 0.61). The key safety endpoint occurred in 25.1% and 27.8%, respectively (p
= 0.53). However, after 1 year valve thrombosis was reported in 8 (2.5%) patients
in the DAPT group but not in the OAC group (p = 0.02). CONCLUSIONS: OAC after
TAVR seems to reduce the risk of clinical valve thrombosis without a statisti
cally significant increase in bleeding complications.
PMID- 28497846
TI - Survival after Second and Subsequent Recurrences in Osteosarcoma: A Retrospective
Multicenter Analysis.
AB - Purpose Osteosarcoma (OS) is the most common primary bone tumor. Despite complete
surgical removal and intensive chemotherapeutic treatment, 30%-35% of patients
with OS have local or systemic recurrence. Some patients survive multiple
recurrences, but overall survival after OS recurrence is poor. This analysis aims
to describe and identify factors influencing post-relapse survival (PRS) after a
second OS relapse. Methods This is a retrospective analysis of 60 patients with a
second relapse of OS of the extremities in 2 Italian centers between 2003 and
2013. Results Treatment for first and subsequent relapses was planned according
to institutional guidelines. After complete surgical remission (CSR) following
the first recurrence, patients experienced a second OS relapse with a median
disease-free interval (DFI) of 6 months. Lung disease was prevalent: 44 patients
(76%) had pulmonary metastases. Survival after the second relapse was 22% at 5
years. Lung disease only correlated with better survival at 5 years (33.6%)
compared with other sites of recurrence (5%; p = 0.008). Patients with a single
pulmonary lesion had a better 5-year second PRS (42%; p = 0.02). Patients who
achieved a second CSR had a 5-year second PRS of 33.4%. Chemotherapy (p<0.001)
benefited patients without a third CSR. Conclusions This analysis confirms the
importance of an aggressive, repeated surgical approach. Lung metastases only,
the number of lesions, DFI and CSR influenced survival. It also confirms the
importance of chemotherapy in patients in whom surgical treatment is not
feasible.
PMID- 28497847
TI - Pathogenesis, clinical manifestations and management of immune checkpoint
inhibitors toxicity.
AB - Immune checkpoint inhibitors have emerged as an effective treatment for several
tumor types and their use in clinical practice is expected to further increase in
the immediate future. Although these agents are well tolerated, they are
associated with a peculiar spectrum of toxicity, which is immune mediated and may
potentially affect every organ. However, immune-related adverse events are mostly
reversible if promptly diagnosed and adequately treated. Therefore, it is crucial
that medical oncologists know how to diagnose and treat immune-related adverse
events. This review focuses on the pathogenesis, clinical manifestations and
management of immune-related toxicity of anti-CTLA-4 and anti-PD-1 antibodies.
PMID- 28497848
TI - Isolation of subtelomeric sequences of porcine chromosomes for translocation
screening reveals errors in the pig genome assembly.
AB - Balanced chromosomal aberrations have been shown to affect fertility in most
species studied, often leading to hypoprolificacy (reduced litter size) in
domestic animals such as pigs. With an increasing emphasis in modern food
production on the use of a small population of high quality males for artificial
insemination, the potential economic and environmental costs of hypoprolific
boars, bulls, rams etc. are considerable. There is therefore a need for novel
tools to facilitate rapid, cost-effective chromosome translocation screening.
This has previously been achieved by standard karyotype analysis; however, this
approach relies on a significant level of expertise and is limited in its ability
to identify subtle, cryptic translocations. To address this problem, we developed
a novel device and protocol for translocation screening using subtelomeric probes
and fluorescence in situ hybridisation. Probes were designed using BACs
(bacterial artificial chromosomes) from the subtelomeric region of the short (p
arm) and long (q-arm) of each porcine chromosome. They were directly labelled
with FITC or Texas Red (p-arm and q-arm respectively) prior to application of a
'Multiprobe' device, thereby enabling simultaneous detection of each individual
porcine chromosome on a single slide. Initial experiments designed to isolate
BACs in subtelomeric regions led to the discovery of a series of incorrectly
mapped regions in the porcine genome assembly (from a total of 82 BACs, only 45
BACs mapped correctly). Our work therefore highlights the importance of accurate
physical mapping of newly sequenced genomes. The system herein described allows
for robust and comprehensive analysis of the porcine karyotype, an adjunct to
classical cytogenetics that provides a valuable tool to expedite efficient, cost
effective food production.
PMID- 28497849
TI - Differential investment in body girths by sex: Evidence from 3D photonic scanning
in a Thai cohort.
AB - OBJECTIVES: Life history trade-offs may manifest between competing organs and
tissues in the body. Sexual dimorphism in tissue investment is well-established
in humans, with sex-associated body shape differences linked to natural and
sexual selection. This study uses three-dimensional (3D) photonic scanning to
test whether males and females differentially invest energy in various body
regions in relation to two independent proxies of growth. MATERIALS AND METHODS:
Body shape data (multiple girths) came from a Thai cohort (n = 11,610; 53%
female; age range 21-88 years). Weight was considered a proxy for recent energy
acquisition. Stature represented completed growth, a proxy for energy acquisition
earlier in life. The data were analyzed using growth-proxy by sex interaction log
log regression models adjusting for age, salary and number of children. RESULTS:
For a given percentage increase in weight, females showed greater percentage
increases than males in girths of the arm, chest, hip, thigh, knee and calf (p <
0.001), whilst males exceeded females in head and waist girths (also p < 0.001).
For a given percentage increase in height, weight and all girths showed greater
proportional changes in males than females (p < 0.001). DISCUSSION: These results
indicate sex-specific life history strategies wherein the direction and timing of
energy investment in girths varies between the sexes. The results add to
literature suggesting that sexual dimorphism in body morphology is not a fixed
trait; rather, differential energy allocation to specific body regions appears to
be a plastic strategy adjusted in relation to energy acquisition across the life
course.
PMID- 28497850
TI - Workforce diversity in dentistry - current status and future challenges.
AB - The racial and ethnic diversity of the US oral health care workforce remains
insufficient to meet the needs of an increasingly diverse population and to
address persistent health disparities. The findings from a recent national survey
of underrepresented minority dentists are reviewed and recommendations are made
for enhancing diversity in the dental profession.
PMID- 28497851
TI - A novel mutation in the TYRP1 gene associated with brown coat colour in the
Australian Shepherd Dog Breed.
PMID- 28497852
TI - Patients' perception of disease and experience with type 2 diabetes patient
education in Denmark.
AB - BACKGROUND: Patient education programmes for a range of chronic conditions are
widely implemented, but studies have shown that not all participants benefit
equally from the patient education programmes. AIM: To explore differences in how
persons with diabetes experience diabetes-related patient education programmes.
METHODS: Qualitative in-depth interviews were conducted with eleven participants
6 months after participation in patient education. Using thematic analysis, we
identified three themes: programme elements, interactions between participants
and the role of facilitators. We used Alonzo's theory of Everyday Illness
Behaviour and reported restrictions in daily activities to categorise seven
participants as 'healthy' and four as 'ill' and compare their experiences of
patient education. RESULTS: Although all participants identified information on
diet and exercise as the most beneficial programme element, healthy participants
found this information easy to understand and apply to make healthy changes in
their daily lives. Ill participants found the information difficult to understand
and were much less likely to implement related changes. Healthy participants
valued social interactions occurring during interactive programme components such
as weigh-in sessions, physical exercise and cooking classes. In contrast, ill
participants did not value these social interactions. Healthy participants also
tended to view programme facilitators more positively. Regardless of disease
status, participants found it motivating to compare their health status to that
of participants they perceived as more ill than themselves. CONCLUSION: Patient
education experiences differ according to self-perceived disease status.
Programme facilitators should be sensitive to the possibility that participants
who are more ill may be less likely to perceive patient education as beneficial
and implement new behaviours. Knowledge about factors leading to differences in
patient experiences of chronic disease self-management education programmes is
essential for the development of programmes that benefit all patients. Future
research should explore the value of programmes differentiated for participants
with different levels of health.
PMID- 28497853
TI - Respiratory morbidity among U.S. coal miners in states outside of central
Appalachia.
AB - BACKGROUND: Recent NIOSH publications have focused on the respiratory health of
coal miners in central Appalachia, yet 57% of U.S. coal miners work in other
regions. We characterized respiratory morbidity in coal miners from these
regions. METHODS: Active coal miners working outside of central Appalachia who
received chest radiographs and/or spirometry during 2005-2015 were included.
Chest radiographs were classified according to International Labour Office
standards and spirometry was interpreted using the American Thoracic Society
guidelines. Prevalence of coal workers' pneumoconiosis (CWP) and abnormal
spirometry were compared by region. RESULTS: A total of 103 (2.1%) miners had
CWP. The eastern region had the highest prevalence (3.4%), followed by the
western (1.7%), and interior (0.8%) regions. A total of 524 (9.3%) miners had
abnormal spirometry. CONCLUSIONS: CWP occurs in all U.S. coal mining regions.
Prevalence of CWP was higher in the eastern region, but lower than levels
reported in central Appalachia.
PMID- 28497854
TI - Allergic sinusitis and severe asthma caused by occupational exposure to locust
bean gum: Case report.
AB - We present a case that highlights the difficulties with diagnosis and the dangers
of occupational allergic sinusitis and asthma left unrecognized. We describe the
case history of a man who experienced work-related symptoms 1 year after
beginning work as a cheesemaker at a creamery, and whose respiratory symptoms
progressively worsened over 16 years before an occupational cause of his asthma
was identified. His initial discrete episodes of sinusitis and acute bronchitis
evolved into persistent asthma of increasing severity with exacerbations
requiring repeated emergency room treatment. The case described in our report
emphasizes the importance of clinician diagnosis of OA, and subsequent removal
from exposure, such that asthma severity does not progress to near-fatal or fatal
asthma in the sensitized worker. As demonstrated by this case report,
identification of an occupational cause of asthma relies on a high degree of
suspicion and excellent detective work by the clinician.
PMID- 28497855
TI - Health promotion for people with intellectual disabilities - A concept analysis.
AB - BACKGROUND: Whereas 'health promotion' is a well-known concept for healthcare
professionals, the concept of 'health promotion for people with intellectual
disabilities' and its unique associated challenges are not well understood. AIMS
AND OBJECTIVE: This article provides a systematic analysis of how health
promotion is being conceptualised for people with intellectual disabilities and
how health promotion can work best in the light of this group's specific needs
and limitations. DESIGN: Rodgers' evolutionary concept analysis. METHOD: MEDLINE,
PsycINFO, CINAHL and SocINDEX were searched using the search terms 'health
promotion', 'people with intellectual disabilities' and 'developmental
disabilities'. This review includes studies published between 1992 and 2014. A
total of 52 articles were included. RESULTS: Health promotion for people
intellectual disabilities, as discussed in the literature, focuses on four
aspects, namely supporting a healthy lifestyle, providing health education,
involving supporters and being person-centred. Antecedents of the concept 'health
promotion for people with intellectual disabilities' were healthcare access and
sensitised healthcare providers. The outcomes were improved health, being
empowered, enhanced quality of life and reduced health disparities. CONCLUSION:
This analysis provides a solid foundation for healthcare stakeholders' planning,
implementing and evaluating health-promotion activities for people with
intellectual disabilities at the policy level and in the community.
PMID- 28497856
TI - Case of shift from linear immunoglobulin A bullous dermatosis to pemphigus
herpetiformis for a short period of time.
AB - Pemphigus herpetiformis (PH) is a rare variant of pemphigus characterized by
erythemas and vesicles, tending to present with annular-shaped lesions.
Immunologically, immunoglobulin (Ig)G deposition at the keratinocyte cell
surfaces is observed. Linear IgA bullous dermatosis (LABD) is a rare subepidermal
blistering disease with linear IgA deposits at the epidermal basement membrane
zone (BMZ). The annular-shaped skin lesions in PH mimic clinical manifestation of
other autoimmune bullous diseases, including LABD, although PH and LABD have
different immunological and histopathological features. Herein, we report the
first case of a shift from LABD to PH. A 70-year-old Japanese man presented
annular erythemas surrounded by vesicles on the trunk and extremities.
Histopathological examination revealed subepidermal bullae and eosinophilic
spongiosis. Direct immunofluorescence demonstrated linear IgA deposits at the
epidermal BMZ. Immunoblot analyses of normal human epidermal and dermal extracts,
supernatant of HaCaT cells, recombinant proteins of BP180 NC16a and C-terminal
domains, and purified laminin-332 showed no reactivity for either IgG or IgA. IgG
chemiluminescent enzyme immunoassays for desmogleins 1 and 3, and BP180 were all
negative. These findings led to the diagnosis of sole LABD. Although oral
prednisolone temporarily improved the skin lesions, annular erythema without
vesicles remained. A new skin biopsy revealed subcorneal pustules with
eosinophils, but no subepidermal bullae. Direct immunofluorescence revealed IgG
and C3 deposition at the keratinocyte cell surfaces. IgG enzyme-linked
immunosorbent assay for mammalian desmocollins 1-3 revealed desmocollin 1
reactivity. Based on these findings, we made a diagnosis of sole PH.
PMID- 28497857
TI - Validation of electrical ostial pulmonary vein isolation verified with a spiral
inner lumen mapping catheter during second-generation cryoballoon ablation.
AB - BACKGROUND: Achieve catheters are cryoballoon guidewires that enable pulmonary
vein (PV) potential mapping. The single catheter approach in conjunction with the
Achieve catheter is currently standard practice in second-generation cryoballoon
ablation, yet circumferential mapping catheters are the gold standard for
evaluating PV isolation (PVI). The study sought to validate the ostial PVI
verified by an Achieve catheter alone. METHODS: One hundred fifty-one paroxysmal
atrial fibrillation patients undergoing PVI using exclusively 28-mm second
generation cryoballoons were enrolled. PV recordings were analyzed during (real
time recordings) and after cryoballoon applications with 20-mm Achieve mapping
catheters, and subsequently validated by 20-mm conventional circumferential
mapping catheters. RESULTS: Out of 596 PVs, 576 (96.6%) were isolated using
cryoballoons, and 20 required touch-up ablation. PVI was verified during
cryoballoon applications with real-time monitoring in 299, and after applications
in 280 PVs by Achieve catheters alone. The time-to-isolation was 27.2 +/- 22.0
seconds. Validation with standard circumferential mapping catheters confirmed
ostial PVIs in 296 of 299 (99.0%) PVs that real-time PVI was obtained during
applications, and in 242 of 280 (86.5%) PVs that PV activities were not visible
during applications and PVI was verified after the applications. The accuracy of
ostial PVIs with Achieve catheters in PVs without obtaining real-time PV
recordings was 40/47 (85.1%), 58/65 (89.2%), 77/79 (97.5%), 61/81 (75.3%), and
6/8 (75.0%) in left superior, left inferior, right superior, right inferior, and
left common PVs, respectively. CONCLUSIONS: In second-generation 28-mm
cryoballoon ablation, verification of ostial PVIs using Achieve mapping catheters
alone might not be sufficient to accurately confirm an ostial PVI when real-time
PVI was not obtained.
PMID- 28497858
TI - Beat-to-beat ECG restitution: A review and proposal for a new biomarker to assess
cardiac stress and ventricular tachyarrhythmia vulnerability.
AB - BACKGROUND: Cardiac restitution is the ability of the heart to recover from one
beat to the next. Ventricular arrhythmia vulnerability can occur when the heart
does not properly adjust to sudden changes in rate or in hemodynamics leading to
excessive temporal and/or spatial heterogeneity in conduction or repolarization.
Restitution has historically been used to study, by invasive means, the dynamics
of the relationship between action potential duration (APD) and diastolic
interval (DI) in sedated subjects using various pacing protocols. Even though the
analogous measures of APD and DI can be obtained using the surface ECG to acquire
the respective QT and TQ intervals for ECG restitution, this methodology has not
been widely adopted for a number of reasons. METHODS: Recent development of more
advanced software algorithms enables ECG intervals to be measured accurately, on
a continuous beat-to-beat basis, in an automated manner, and under highly dynamic
conditions (i.e., ambulatory or exercise) providing information beyond that
available in the typical resting state. RESULTS: Current breakthroughs in ECG
technology will allow ECG restitution measures to become a practical approach for
providing quantitative measures of the risks for ventricular arrhythmias as well
as cardiac stress in general. CONCLUSIONS: In addition to a review of the
underlying principles and caveats of ECG restitution, a new approach toward an
advancement of more integrated restitution biomarkers is proposed.
PMID- 28497859
TI - Superlubricity between MoS2 Monolayers.
AB - The ultralow friction between atomic layers of hexagonal MoS2 , an important
solid lubricant and additive of lubricating oil, is thought to be responsible for
its excellent lubricating performances. However, the quantitative frictional
properties between MoS2 atomic layers have not been directly tested in
experiments due to the lack of conventional tools to characterize the frictional
properties between 2D atomic layers. Herein, a versatile method for studying the
frictional properties between atomic-layered materials is developed by combining
the in situ scanning electron microscope technique with a Si nanowire force
sensor, and the friction tests on the sliding between atomic-layered materials
down to monolayers are reported. The friction tests on the sliding between
incommensurate MoS2 monolayers give a friction coefficient of ~10-4 in the regime
of superlubricity. The results provide the first direct experimental evidence for
superlubricity between MoS2 atomic layers and open a new route to investigate
frictional properties of broad 2D materials.
PMID- 28497860
TI - Intermittent preexcitation indicates "a low-risk" accessory pathway: Time for a
paradigm shift?
AB - We report three patients with intermittent loss of the preexcitation pattern in
the ECG that had undergone an electrophysiological study. Despite apparently
poorly conducting accessory pathway (AP), in each case a fast anterograde
conduction, either during spontaneous atrial fibrillation or during incremental
atrial pacing (on isoproterenol) was documented; shortest preexcited RR intervals
of 200-240 ms were observed. We review the literature and conclude that
intermittent preexcitation observed on resting 12-lead ECG lacks sufficient
specificity for the diagnosis of an AP with long refractory period and cannot be
considered a substitute for electrophysiological study in patients with this
electrocardiographical phenomenon.
PMID- 28497861
TI - Corticosteroids for preterm deliveries: missing evidence.
PMID- 28497862
TI - Association between fear of childbirth and maternal acceptance of pregnancy.
AB - AIM: This descriptive study aimed to explore the associations between fear of
childbirth, acceptance of pregnancy and identification with the motherhood role
among primipara women. BACKGROUND: Women who have difficulty accepting their
pregnancy have a harder time adapting to pregnancy and motherhood and experience
more fears related to childbirth. The number of studies conducted on this topic
is limited. METHODS: This study involved 310 pregnant women admitted to a public
hospital in Istanbul between January and June of 2013. A participant
identification form, the Prenatal Self-Evaluation Questionnaire and the Wijma
Delivery Expectancy/Experience Questionnaire Version A were used for data
collection. RESULTS: Pregnant women participating in the study experienced
moderate levels fear of childbirth. Pregnant women who requested caesarean
section experienced more intense fear of childbirth. Fear of childbirth scores
had significant but weak correlations with acceptance of pregnancy and
identification with the motherhood role. CONCLUSION: The findings showed that
acceptance of pregnancy and identification with the motherhood role are weakly
associated with fear of childbirth. IMPLICATIONS FOR NURSING AND HEALTH POLICY:
The results from this study can be used to help: increase awareness among health
professionals (doctors, nurses, midwives) in antenatal care services about a
mother's adaptation to pregnancy and the negative effects of fear of childbirth;
direct future research examining factors affecting adaptation to pregnancy and
fear of childbirth; establish routine assessments for adaptation to pregnancy and
fear of childbirth; provide professional support for women with difficulties
adapting to pregnancy and with fear of childbirth; result in reduced
complications from invasive methods such as caesarean section due to less
requests for these procedures; and promote the health of mothers and babies.
PMID- 28497864
TI - Valbenazine for tardive dyskinesia: A systematic review of the efficacy and
safety profile for this newly approved novel medication-What is the number needed
to treat, number needed to harm and likelihood to be helped or harmed?
AB - OBJECTIVE: The objective of this systematic review was to describe the efficacy,
tolerability, and safety of valbenazine for the treatment of tardive dyskinesia
(TD). DATA SOURCES: The pivotal registration trials were accessed by querying
http://www.ncbi.nlm.nih.gov/pubmed/ and http://www.clinicaltrials.gov, for the
search terms 'valbenazine' OR 'NBI-98854', and by also querying the EMBASE
(Elsevier) commercial database for clinical poster abstracts, and by asking the
manufacturer for copies of posters presented at congresses. Product labeling
provided additional information. STUDY SELECTION: All available clinical reports
of studies were identified. DATA EXTRACTION: Descriptions of the principal
results and calculation of number needed to treat (NNT) and number needed to harm
(NNH) for relevant dichotomous outcomes were extracted from the available study
reports and other sources of information. DATA SYNTHESIS: Valbenazine, a
reversible inhibitor of Vesicular Monoamine Transporter Type 2 (VMAT2), received
approval for the treatment of TD in adults based on a clinical trial development
programme that included three 6-week parallel group, randomised, placebo
controlled studies, including one Phase III trial described in product labeling.
The recommended dose for valbenazine is 80 mg/d. The percentage of responders in
the Phase III acute study, as defined by >=50% reduction from baseline in the
Abnormal Involuntary Movement Scale dyskinesia score was 40.0% for valbenazine 80
mg/d vs 8.7% for placebo, yielding a NNT of 4 (95% CI 3-6). As pooled from
available data, discontinuation rates because of an adverse event were 2.9% for
valbenazine-treated patients vs 1.6% for placebo-treated patients, resulting in a
NNH of 76 (ns). The only adverse event that met the threshold of incidence >=5%
for valbenazine and a rate of >=2 times than that observed with placebo was
somnolence (somnolence, fatigue, sedation), with rates of 10.9% for valbenazine
(all doses) vs 4.2% for placebo, resulting in a NNH of 15 (95% CI 9-52). An
additional warning and precaution is that valbenazine can prolong the ECG QT
interval, however, the valbenazine product label does not contain any bolded
boxed warnings or contraindications. CONCLUSIONS: Valbenazine is presently the
only US Food and Drug Administration-approved agent specifically indicated for
the treatment of TD. Valbenazine is about 15 times more likely to result in a
response than in a discontinuation because of an adverse event. Head-to-head
comparisons with other VMAT2 inhibitors among patients with TD in the 'real
world' are needed.
PMID- 28497863
TI - CTLA-4 expressed by FOXP3+ regulatory T cells prevents inflammatory tissue attack
and not T-cell priming in arthritis.
AB - Cytotoxic T-lymphocyte antigen 4 (CTLA-4) -mediated regulation of already
tolerized autoreactive T cells is critical for understanding autoimmune
responses. Although defects in CTLA-4 contribute to abnormal FOXP3+ regulatory T
(Treg) cell function in rheumatoid arthritis, its role in autoreactive T cells
remains elusive. We studied immunity towards the dominant collagen type II (CII)
T-cell epitope in collagen-induced arthritis both in the heterologous setting and
in the autologous setting where CII is mutated at position E266D in mouse
cartilage. CTLA-4 regulated all stages of arthritis, including the chronic phase,
and affected the priming of autologous but not heterologous CII-reactive T cells.
CTLA-4 expression by both conventional T (Tconv) cells and Treg cells was
required but while Tconv cell expression was needed to control the priming of
naive autoreactive T cells, CTLA-4 on Treg cells prevented the inflammatory
tissue attack. This identifies a cell-type-specific time window when CTLA-4
mediated tolerance is most powerful, which has important implications for
clinical therapy with immune modulatory drugs.
PMID- 28497865
TI - Predictors and implications of early left ventricular ejection fraction
improvement in new-onset idiopathic nonischemic cardiomyopathy with narrow QRS
complex: A NEOLITH substudy.
AB - BACKGROUND: Predictors and implications of early left ventricular ejection
fraction (LVEF) improvement with guideline-directed medical therapy (GDMT) in new
onset idiopathic nonischemic cardiomyopathy (NICM) with narrow QRS complex are
not well described. The objectives were to describe predictors of LVEF
improvement after 3 months on GDMT and adverse cardiac events based on post-GDMT
LVEF status (<=35% vs. >35%). METHODS: A retrospective cohort study was performed
in subjects with new-onset NICM, LVEF <=35%, and narrow QRS complex. Associations
for baseline variables with post-GDMT LVEF improvement and absolute change in
LVEF (?LVEFGDMT ) were assessed. Cox proportional hazards models assessed
associations for post-GDMT LVEF status with adverse cardiac events. RESULTS: In
70 subjects, 31 (44%) had post-GDMT LVEF <=35% after a median follow-up time of
97.5 days (interquartile range, 84-121 days). In final multivariable models,
severely dilated left ventricular end-diastolic diameter (LVEDD), compared with
normal LVEDD, strongly predicted post-GDMT LVEF <=35% (odds ratio, 7.77; 95%
confidence interval [CI], 1.39-43.49; p = .02) and ?LVEFGDMT (beta = -15.709;
standard error = 4.622; p = .001). Subjects with post-GDMT LVEF <=35% were more
likely to have adverse cardiac events over a median follow-up time of 970.5 days
(unadjusted hazard ratio, 2.15; 95% CI, 0.93-4.96; p = .07). In the post-GDMT
LVEF <=35% group, 9 of 26 subjects (35%) had long-term LVEF > 35%. CONCLUSION: In
new-onset NICM with narrow QRS complex, nondilated LVEDD predicted early LVEF
improvement. Those with post-GDMT LVEF <=35% had higher risk of adverse cardiac
events, but a substantial proportion demonstrated continued long-term LVEF
improvement.
PMID- 28497866
TI - Evaluation of a new commercial von Willebrand factor multimer assay.
PMID- 28497867
TI - The mystery of the missing warbler.
PMID- 28497869
TI - Increased delta neutrophil index in women with severe preeclampsia.
AB - PROBLEM: The pathophysiology of preeclampsia (PE) is believed to be associated
with a systemic inflammatory response, but few inflammatory markers are currently
available to predict PE. Therefore, the aim of this study was to compare the
serum delta neutrophil index (DNI) between normal and preeclamptic women.
METHODS: Sixty-five patients with mild preeclampsia (mPE), 147 patients with
severe preeclampsia (sPE), and 163 women with normal pregnancy were included in
this study. Maternal laboratory values including DNI were compared among the
three groups. RESULTS: The mean DNI was significantly higher in the sPE group,
but there was no significant difference between the normal pregnancy group and
mPE. The DNI also showed positive correlation with systolic and diastolic blood
pressures, mean arterial pressure, proteinuria during 24 hours, proteinuria in
dipstick, and ominous symptoms. CONCLUSION: The serum DNI value was increased in
women with severe preeclampsia compared to that in those with normal pregnancy or
mild preeclampsia. Further studies are needed to evaluate application of the DNI
value as a prognostic marker of preeclampsia.
PMID- 28497868
TI - Person-centred care dialectics-Inquired in the context of palliative care.
AB - Although a widely used concept in health care, person-centred care remains
somewhat ambiguous. In the field of palliative care, person-centred care is
considered a historically distinct ideal and yet there continues to be a dearth
of conceptual clarity. Person-centred care is also challenged by the pull of
standardization that characterizes much of health service delivery. The
conceptual ambiguity becomes especially problematic in contemporary pluralistic
societies, particularly in the light of continued inequities in healthcare access
and disparities in health outcomes. Our aim was to explicate premises and
underlying assumptions regarding person-centred care in the context of palliative
care with an attempt to bridge the apparently competing agendas of
individualization versus standardization, and individuals versus populations. By
positioning person-centredness in relation to the hermeneutics of the self
according to Paul Ricoeur, dialectics between individualization and
standardization, and between individuals and populations were constructed. The
competing agendas were related in a dialectic manner in the way that population
health is of importance for the individual, and standardization is of importance
for the population. The analysis suggests that person-centred care is an ethical
stance, which gives prominence to both suffering and capability of the individual
as a person. The dialectic analysis points towards the importance of extending
person-centred care to encompass population and societal perspectives and thereby
avoiding a problematic tendency of affiliating person-centred care with
exclusively individualistic perspectives. Considerations for person-centred
palliative care on micro-, meso- and macrolevels conclude the paper.
PMID- 28497870
TI - Issues in reproductive health in females having inherited bleeding disorders in
Pakistan.
PMID- 28497872
TI - Deviant burials and social identity in a postmedieval Polish cemetery: An
analysis of stable oxygen and carbon isotopes from the "vampires" of Drawsko.
AB - OBJECTIVES: Deviant burials can reveal important information about both social
and individual identity, particularly when the mortuary record is supplemented by
an examination of skeletal remains. At the postmedieval (17th to 18th c. AD)
cemetery of Drawsko (Site 1), Poland, six individuals (of n = 285) received
deviant, anti-vampiristic mortuary treatment. A previous study using radiogenic
strontium isotope ratios ( x-= 0.7112 +/- 0.0006, 1sigma, n = 60) found that
these "vampires" were in fact locals, not migrants to the region targeted for
deviant burial due to their status as immigrant outsiders. However, considerable
geologic overlap in strontium isotope ratios across the North European Plain may
have masked the identification of at least some nonlocal individuals. This study
further contextualizes strontium isotope ratios using additional biogeochemical
data to test the hypothesis that additional nonlocals were present in the Drawsko
cemetery. METHODS: Stable oxygen and carbon isotopes from the dental enamel of 58
individuals interred in both normative and atypical burials at Drawsko were
analyzed. RESULTS: Both delta18 Oc(VPDB) ( x-= -4.5 +/- 0.70/00) and delta13 Cap
isotope values ( x-= -13.6 +/- 0.80/00) displayed little variability and were not
significantly different between vampire and normative burials, supporting prior
strontium results of a largely local population. Nevertheless, homogeneity in
oxygen isotope values across other northern European sites makes it difficult to
speculate about isotopic regional diversity, leaving open the possibility that
additional migrants to the region remain undetected. Additionally, carbon isotope
values point to a locally sourced diet dominated by C3 resources but with some
supplementation by C4 goods that likely included millet, fitting with historic
descriptions of postmedieval diet in Poland. CONCLUSIONS: Those interred as
vampires appear local to the region and thus likely underwent deviant funerary
treatment due to some other social stigma not apparent from the skeleton.
PMID- 28497873
TI - An online education approach to population health in a global society.
AB - BACKGROUND: Health professions education content must keep pace with the ever
evolving and changing health care system. Population-based health care is
advocated as a way to improve health outcomes, particularly in a technologically
advanced health system like the United States. At the same time, global health
knowledge is increasingly valued in health professions education, including
nursing. AIMS: This article describes the design and implementation of an online
population health course with a global viewpoint intended to accommodate the need
for improved knowledge and skill application for graduate nurses. Attention was
also given to faculty efficiency during the process of design and implementation.
MATERIALS AND METHODS: This population-global health course was piloted in a
renovated master's curriculum for two semesters. Administering a Course
Improvement Survey after initial course offerings assisted faculty to assess and
target essential course changes. Data were collected from 106 registered nurse
graduate students. RESULTS: Population and global health course objectives were
met and students identified areas for course enhancement. Students (90%-94%)
reported achieving increased knowledge of population health and global health.
DISCUSSION: Like other creative works, the first rendition of a course requires
pedagogical adjustments and editing. Formal student input, when built into the
design and implementation of a course can assist faculty to be efficient when
crafting essential course changes for subsequent semesters. Data from the survey
showed that major population and global subject matter was being grasped by
students, the data also revealed that tweaking specific online strategies like
making all course content mobile would enhance the course. CONCLUSION: The course
development process and course improvement evaluation for this Population Health
in a Global Society course proved valuable in the education of nurses, and helped
maintain faculty work efficiency.
PMID- 28497874
TI - Serum angiopoietin-2 level as a potential biomarker in psoriasis vulgaris.
PMID- 28497875
TI - Comparison of the tracheal systems of Anopheles sinensis and Aedes togoi larvae
using synchrotron X-ray microscopic computed tomography (respiratory system of
mosquito larvae using SR-MUCT).
AB - Mosquito-borne diseases, such as malaria, dengue fever, and Zika virus, are
serious global health issues. Vector control may be an important strategy in
reducing the mortality caused by these diseases. The respiratory system of
mosquito larvae in the water has to inhale atmospheric oxygen as aquatic
organisms. In this study, the three-dimensional (3D) structures of the dorsal
longitudinal trunks (DLTs) of the tracheal systems of Anopheles sinensis and
Aedes togoi were compared using synchrotron X-ray microscopic computed
tomography. DLT respiratory frequencies were also investigated. Interestingly,
the larvae of the two mosquito species exhibit tracheal systems that are both
morphologically and functionally distinct. A. sinensis hangs horizontally under
the water surface, and has a smaller DLT volume than A. togoi. In contrast, A.
togoi hangs upside down using a siphon by fixing its tip to the water surface.
The frequency of peristaltic movement in A. togoi is higher than that of A.
sinensis. These differences in the structures and breathing behaviors of the
respiratory systems of mosquito larvae provide new insights into the tracheal
systems of mosquito larvae, which should help develop novel effective control
strategies targeting mosquito larvae.
PMID- 28497876
TI - Morphological variations on microscopy in oocysts of coccidian parasites: A
prospective study from a tertiary care hospital in north India.
AB - The modified acid fast staining technique is a commonly used procedure for the
detection of coccidian parasites in developing countries. The morphological
variations observed in these parasites play a significant role to some extent in
both identification and diagnosis of these parasitic infections. A prospective
cross sectional study was performed over three years. The fecal smears were
stained by modified Kinyoun acid-fast staining technique and were extensively
studied for morphological variations in the coccidian parasites. Out of a total
of two thousand one hundred fifty one (n = 2,151) fecal samples received during
the study period, 259 samples (12%) were positive for any one of the coccidian
parasites. Morphological variations, especially in the staining character was
noted in all the three coccidian parasites. This study was an attempt to
characterize different variations in size, shape and staining characteristics of
the three coccidian parasites.
PMID- 28497877
TI - Electrical stimulation of the dorsal columns of the spinal cord for Parkinson's
disease.
AB - Spinal cord stimulation has been used for the treatment of chronic pain for
decades. In 2009, our laboratory proposed, based on studies in rodents, that
electrical stimulation of the dorsal columns of the spinal cord could become an
effective treatment for motor symptoms associated with Parkinson's disease (PD).
Since our initial report in rodents and a more recent study in primates, several
clinical studies have now described beneficial effects of dorsal column
stimulation in parkinsonian patients. In primates, we have shown that dorsal
column stimulation activates multiple structures along the somatosensory pathway
and desynchronizes the pathological cortico-striatal oscillations responsible for
the manifestation of PD symptoms. Based on recent evidence, we argue that
neurological disorders such as PD can be broadly classified as diseases emerging
from abnormal neuronal timing, leading to pathological brain states, and that the
spinal cord could be used as a "channel" to transmit therapeutic electrical
signals to disrupt these abnormalities. (c) 2017 International Parkinson and
Movement Disorder Society.
PMID- 28497878
TI - Pharmacist prescribing: a cross-sectional survey of the views of pharmacists in
Nigeria.
AB - OBJECTIVES: This study was carried out to: (1) explore the views of pharmacists
in Nigeria on the extension of prescribing authority to them and determine their
willingness to be prescribers and (2) identify the potential facilitators and
barriers to introducing pharmacist prescribing in Nigeria. METHOD: An online
cross-sectional survey was conducted from August to October 2014 among 775
pharmacists recruited from the Facebook group of the Pharmaceutical Society of
Nigeria using a simple random technique. The questionnaire used for the survey
was developed based on the review of the literature and previous qualitative
studies conducted in Nigeria. The instrument was evaluated for content validity
by two external pharmacy practice researchers and the reliability of items
assessed using internal consistency tests. Data obtained from the survey were
entered into SPSS v.22, and descriptive statistics were generated. Relationships
between variables were evaluated using the chi-square test, and P < 0.05 was
considered statistically significant. KEY FINDINGS: The response rate was 40.6%
(315/775). Three hundred and six (97.1%) respondents agreed that pharmacists
should be given prescribing authority. Of these 306, 295 (96.4%) were willing to
be prescribers, and just over half of them (148/295; 50.2%) would prefer to
prescribe in collaboration with medical doctors. Of those willing to be
prescribers, 285 (96.6%) reported that they would need additional training. The
most perceived areas of training needed were in the principles of differential
diagnosis (81.4%), pathophysiology of diseases (74.0%) and interpretation of
laboratory results (68.1%). Respondents identified increasing patients' access to
care (308/315; 97.8%) and better utilisation of pharmacists' skills (307/315;
97.5%) as the most likely facilitators to pharmacist prescribing in Nigeria. On
the other hand, resistance from the medical doctors (299/315; 94.9%) and
pharmacists' inadequate skills in diagnosis (255/315; 81.0%) were perceived as
the most likely barriers. CONCLUSION: Pharmacist prescribing represents an
opportunity to promote patients' access to care and the utilisation of
pharmacists' skills in Nigeria. The majority of pharmacists showed a positive
attitude towards pharmacist prescribing and were willing to be prescribers. The
findings of this study could potentially contribute to future medicine
prescribing policy and pharmacy practice in Nigeria.
PMID- 28497879
TI - Bone morphogenetic protein-5, a key molecule that mediates differentiation in
MC3T3E1 osteoblast cell line.
AB - Bone morphogenetic protein-5 (BMP-5) is a member of the TGF receptor-beta family
with osteoinductive property. However, its physiological role in osteoblast
differentiation is not defined. This study highlights the importance of BMP-5 in
MC3T3E1 osteoblast differentiation. Pre-osteoblasts exposed to osteogenic media
(ascorbic acid, 50 ug/ml and beta-glycerophosphate, 10 mM) showed high protein
expression of BMP-5 in cell lysates and cell culture supernatants, which peaked
during early time-points of differentiation and declined with onset of
mineralization. Attenuation of endogenous BMP-5 protein expression by RNA
interference downregulated the expression of type I collagen (COLIA1), an early
osteoblast differentiation marker but not osteocalcin, a late osteoblast
differentiation marker. Further experiments to analyze the cell signaling
components revealed that BMP-5 modulates COLIA1 expression via p38-Runx2 axis
involving Runx2 (Ser19) phosphorylation. These effects were also observed when
recombinant BMP-5 was added to pre-osteoblast cultures reinforcing the fact that
BMP-5 is a modulator of COLIA1 expression. We conclude that BMP-5 has stage
specific role to play during MC3T3E1 osteoblast differentiation in part by
autocrine p38/Runx2/COLIA1 signaling. (c) 2017 BioFactors, 43(4):558-566, 2017.
PMID- 28497880
TI - Ambient Protection of Few-Layer Black Phosphorus via Sequestration of Reactive
Oxygen Species.
AB - Few-layer black phosphorous (BP) has emerged as a promising candidate for next
generation nanophotonic and nanoelectronic devices. However, rapid ambient
degradation of mechanically exfoliated BP poses challenges in its practical
deployment in scalable devices. To date, the strategies employed to protect BP
have relied upon preventing its exposure to atmospheric conditions. Here, an
approach that allows this sensitive material to remain stable without requiring
its isolation from the ambient environment is reported. The method draws
inspiration from the unique ability of biological systems to avoid photo
oxidative damage caused by reactive oxygen species. Since BP undergoes similar
photo-oxidative degradation, imidazolium-based ionic liquids are employed as
quenchers of these damaging species on the BP surface. This chemical
sequestration strategy allows BP to remain stable for over 13 weeks, while
retaining its key electronic characteristics. This study opens opportunities to
practically implement BP and other environmentally sensitive 2D materials for
electronic applications.
PMID- 28497881
TI - Efficacy of intrauterine perfusion of granulocyte colony-stimulating factor (G
CSF) for Infertile women with thin endometrium: A systematic review and meta
analysis.
AB - This meta-analysis aimed to explore the efficiency of intrauterine perfusion of
granulocyte colony-stimulating factor (G-CSF) on infertile women with thin
endometrium. Following PRISMA protocol, we conducted a comprehensive search of
academic literatures on various databases including PubMed, EMbase, and Cochrane
Library. Studies published in English before July 1, 2016 were included for
primary screening. Data on the thickness of endometrium, cycle cancelation
rate,clinical pregnancy rate, and embryo implantation rate were extracted and
analyzed, respectively. Eleven eligible studies involving 683 patients were
included in this meta-analysis. Compared with control group, G-CSF perfusion
could significantly improve endometrial thickness (mean difference [MD]=1.79, 95%
confidence interval (CI): 0.92-2.67), clinical pregnancy rate (risk ratio
[RR]=2.52, 95% CI: 1.39-4.55), and embryo implantation rate (RR=2.35, 95% CI:
1.20-4.60), while it could decrease cycle cancelation rate (RR=0.38, 95% CI: 0.25
0.58). Funnel plots revealed that there was no evidence of publication bias. The
current data indicate that intrauterine perfusion of G-CSF can improve
endometrial thickness, clinical pregnancy rate, and embryo implantation rate, but
decrease the cycle cancelation rate in women with thin endometrium.
PMID- 28497882
TI - Identification of the 2-tridecanone cis-acting element in the promoter of
cytochrome P450 CYP6B7 in Helicoverpa armigera.
AB - The expression level of cytochrome P450 genes in insects can be induced by plant
allelochemicals, which is important for insects to adapt to host plants.
Cytochrome P450 CYP6B7 has been reported to be involved in pyrethroid insecticide
resistance in Helicoverpa armigera, and its transcription level was induced by
some inducers. Currently, the regulatory mechanism of the induced expression of
CYP6B7 remains unknown, although it is very important for understanding the
detoxification mechanism to allelochemicals in host plants. The objective of the
present study was to investigate the cis-acting element in the promoter of CYP6B7
mediating the inducible up-regulation of CYP6B7 in H. armigera by 2-tridecanone.
The promoter region of CYP6B7 was cloned by genome walking technique and analyzed
by transient transfection assay. Progressive 5' deletion of the promoter region
of CYP6B7 revealed that the relative luciferase activity of construct -320/+232
could be significantly induced by 2-tridecanone. Further stepwise deletion
between -320 and -238 bp found that construct -292/+232 could also be
significantly induced by 2-tridecanone, but the adjacent construct -256/+232
could not, suggesting the essential role of the sequence between -292 and -257 bp
for 2-tridecanone induction. Nucleotide mutations between -292 and -281 bp had no
influence on the induction effect by 2-tridecanone, but nucleotide mutations
between -280 and -257 bp significantly decreased the induction effect. These
results demonstrated that the cis-acting element for 2-tridecanone induction was
between -280 and -257 bp in the promoter of CYP6B7.
PMID- 28497883
TI - Laser-Induced Graphene in Controlled Atmospheres: From Superhydrophilic to
Superhydrophobic Surfaces.
AB - The modification of graphene-based materials is an important topic in the field
of materials research. This study aims to expand the range of properties for
laser-induced graphene (LIG), specifically to tune the hydrophobicity and
hydrophilicity of the LIG surfaces. While LIG is normally prepared in the air,
here, using selected gas atmospheres, a large change in the water contact angle
on the as-prepared LIG surfaces has been observed, from 0 degrees
(superhydrophilic) when using O2 or air, to >150 degrees (superhydrophobic) when
using Ar or H2 . Characterization of the newly derived surfaces shows that the
different wetting properties are due to the surface morphology and chemical
composition of the LIG. Applications of the superhydrophobic LIG are shown in
oil/water separation as well as anti-icing surfaces, while the versatility of the
controlled atmosphere chamber fabrication method is demonstrated through the
improved microsupercapacitor performance generated from LIG films prepared in an
O2 atmosphere.
PMID- 28497884
TI - Catalytic Enantioselective Arylation and Heteroarylation of Ketones with
Organotitanium Reagents Generated In Situ.
AB - A practical and useful, catalytic enantioselective method has been developed for
the synthesis of tertiary diaryl and aryl heteroaryl carbinols starting from
commercially available aromatic ketones and aryl or heteroaryl bromides. In this
method, organotitanium reagents are generated in situ from the bromides by
lithiation with nBuLi followed by transmetallation of the resulting
organolithiums with ClTi(OiPr)3 . Treatment of the ketones with the titanium
reagents in the presence of (R)-3-(3,5-bistrifluoromehthylphenyl)-1,1'-bi-2
naphthol (BTFP-BINOL) affords the corresponding tertiary alcohols in high
enantioselectivities and yields. The reaction can also start with furan and 2
thienyllithium. The method is operationally simple and can be conducted on a 10
mmol scale without any difficulties.
PMID- 28497886
TI - Acquired von Willebrand syndrome in haematologic malignancies - how the clinical
laboratory correlation improves a challenging diagnosis - a case series.
PMID- 28497885
TI - Larval interference competition between the native Neotropical mosquito Limatus
durhamii and the invasive Aedes aegypti improves the fitness of both species.
AB - Interspecific competition with native species during biological invasions can
sometimes limit alien expansion. We aimed to determine the potential ecological
effects of Limatus durhamii Theobald 1901, a native Neotropical mosquito
(Diptera: Culicidae) species, on the invasive species Aedes (Stegomyia) aegypti
(Linnaeus 1762) that breeds in the same artificial water containers. Development
time and adult dry mass were measured in 3 rearing conditions: control (a single
larva), intraspecific competition (2 conspecific larvae), and interspecific
competition (2 heterospecific larvae). Food was provided ad libitum to eliminate
exploitative competition. For Ae. aegypti, development time was not affected by
interspecific interference competition (nonsignificant differences with the
control) and the adult dry mass was significantly higher, meaning that individual
fitness likely increased. Yet, because previous studies showed longer development
time and lighter adults during competition with other invasive mosquitoes, it is
likely that Ae. aegypti can express a different phenotype depending on the
competing species. The similar pattern found for Li. durhamii females and the
nonsignificant difference with the control for males explain in part why this
species can compete with Ae. aegypti.
PMID- 28497887
TI - Surviving moment to moment: The experience of living in a state of ambivalence
for those with recurrent suicide attempts.
AB - OBJECTIVE: This qualitative study aimed to capture the experience of living in
the ambivalent space between life and death for adults with recurrent suicide
attempts (RSA). It sought to expand upon an earlier study that explored the
processes involved in transitioning away from RSA among adults, which revealed
that occupying this ambivalent space is a crucial part of this process. DESIGN:
Interpretive phenomenological analysis (IPA) was used. This methodology was
designed to explore the lived experiences and meaning making and enabled
interpretation of the multidimensional subjective experiences of RSA
participants. METHODS: In-depth semi-structured interviews were conducted with
eight adult women with a history of RSA who had participated in a therapeutic
intervention at the research site (Skills for Safer Living: A
Psychosocial/Psychoeducational Intervention for People with Recurrent Suicide
Attempts [SfSL/PISA]). The six stages of IPA were followed to analyse the
interview data. RESULTS: Analysis revealed the superordinate theme, 'surviving
moment to moment', which refers to a precarious state of making decisions about
one's life and destiny on a moment-to-moment basis without clear commitment to
either life or death. Two subordinate themes were identified: 'deciding not to
die in the moment' when the participants were more invested in dying than living
and 'deciding to live in the moment' when they were more invested in living than
dying. CONCLUSION: The study illuminated the complex process of making decisions
about ones' destiny on a moment-to-moment basis. It revealed the torment
experienced when occupying this state, while paradoxically, also revealing how
indecision about life and death provided a lifeline opportunity for those with
RSA. Clinicians who recognize the subtle distinctions associated with this in
between state can tailor their interventions accordingly. PRACTITIONER POINTS:
Surviving moment to moment is characterized by a state of emotional flux and
uncertainty about one's destiny, where the person has not fully committed to
either life or death. Within this state, there are two interlinked subprocesses,
whereby the person is leaning more towards death or life. A critical feature in
working with this client group is to recognize their ambiguity and the fragility
and temporality of their decisions about their destiny. The practitioner has an
opportunity to be a catalyst in the momentum towards life by demonstrating
understanding of this survival struggle and tailoring intervention to fit with
the nuanced processes within this state.
PMID- 28497888
TI - Gender equity imbalance in electrocardiology: A call to action.
PMID- 28497889
TI - Selective Separation of Aliphatic Nitriles by Employing a Two-Dimensional
Interdigitated Coordination Polymer.
AB - A room-temperature slow diffusion reaction of the metal nitrates [M=ZnII and CoII
] with 5-azido isophthalic acid (AIPA) and 1,4-bis(4-pyridyl)-2,3-diaza-1,3
butadiene (BPDB) resulted in a new two-dimensional interdigitated coordination
polymer, [M(C8 H3 N3 O4 )(C12 H10 N4 )]?DMF [DMF=dimethyl formamide (C3 H7 NO)].
The non-bonded DMF molecules were found to exchange through a single-crystal to
single-crystal (SCSC) fashion with many aliphatic nitrile compounds. More
importantly, the present compound, I?DMF(Zn) appears to absorb cis-crotononitrile
selectively from the cis/trans mixture as well as a mixture containing the
structural isomer (allylnitrile). It also preferentially absorbs propionitrile
from an equimolar mixture of acetonitrile, propionitrile, and butyronitrile
(1:2:1). The cobalt compound exhibits anti-ferromagnetic behavior.
PMID- 28497890
TI - Direct Asymmetric Alkylation of Ketones: Still Unconquered.
AB - The alkylation of ketones is taught at basic undergraduate level. In many cases
this transformation leads to the formation of a new stereogenic center. However,
the apparent simplicity of the transformation is belied by a number of problems.
So much so, that a general method for the direct asymmetric alkylation of ketones
remains an unmet target. Despite the advancement of organocatalysis and
transition-metal catalysis, neither field has provided an adequate solution.
Indeed, even use of an efficient and general stoichiometric chiral reagent has
yet to be reported. Herein we describe the state-of-the-art in terms of direct
alkylation reactions of some carbonyl groups. We outline the limited progress
that has been made with ketones, and potential routes towards ultimately
achieving a widely applicable methodology for the asymmetric alkylation of
ketones.
PMID- 28497892
TI - Echoes of others: A path analytic examination of an interpersonal-cognitive model
of voice-related distress.
AB - OBJECTIVES: Cognitive models propose that levels of distress associated with
auditory verbal hallucinations ('voices') are influenced by the hearers' beliefs
about their voices (perceived malevolence and omnipotence), their negative
beliefs about themselves and others and their attachment style. This study aims
to test a comprehensive model of the relationship between these variables in
order to identify distal and proximal interpersonal and cognitive factors
contributing to voice-related distress. This interpersonal-cognitive model of
voices proposes that attachment anxiety/avoidance drive negative beliefs about
self and others, which in turn lead to persecutory (malevolent/omnipotent)
beliefs about voices, which in turn increase levels of voice-related distress.
DESIGN/METHODS: Path analysis was used to test the interpersonal-cognitive model
in a sample of 180 people currently hearing voices (57% self-reported
schizophrenia-spectrum diagnoses; 90% some form of self-reported mental health
diagnosis). RESULTS: Path analysis provided support for a model in which there
were direct pathways from attachment anxiety and avoidance to negative beliefs
about self and others; direct pathways from negative beliefs about self and
others to persecutory beliefs about voices; and a direct path from persecutory
beliefs about voices, and negative beliefs about self, to voice distress.
CONCLUSIONS: Findings add support to the suggestion that voice-related distress
occurs in the context of an insecure attachment style and negative core beliefs
about self/others. A therapeutic focus on beliefs about voices, attachment style
and core beliefs about self/others may be important to minimize voice-related
distress. Further tests of this model that can establish causal relationships
between variables are now needed. PRACTITIONER POINTS: Distress associated with
auditory verbal hallucinations ('voices') is highly variable. This study tests a
comprehensive interpersonal-cognitive model of voice distress using path analysis
with 180 participants. The model tested in the current paper shows that
attachment style predicts negative beliefs about self and others, which in turn
predicts negative beliefs about voices, which in turn predicts voice-related
distress. Findings support the suggestion that voice-related distress occurs in
the context of an insecure attachment style and negative core beliefs about self
and others. In addition to focusing on beliefs about voices, a therapeutic focus
on attachment style and core beliefs about self and others may be important in
order to minimize voice-related distress.
PMID- 28497891
TI - Does adenomatous polyposis coli gene promoter 1A methylation increase non-small
cell lung cancer risk? A meta-analysis.
AB - BACKGROUND: The promoter region of the adenomatous polyposis coli (APC) gene is
hypermethylated in several types of cancers, including non-small cell lung cancer
(NSCLC). The prevalence of methylation in the promoter region of this gene in
tumor tissues and autologous controls has not been consistent in previous
studies. We evaluated the frequency of APC gene promoter 1A methylation between
tumor tissues and autologous controls in NSCLC patients by meta-analysis.
METHODS: Open published studies of APC gene promoter 1A methylation between tumor
tissues and autologous samples in NSCLC patients were identified using a
systematic search. Odds ratios (OR) and 95% confidence intervals (CI) of APC gene
promoter 1A methylation in lung cancer tissues versus autologous controls were
calculated. Fourteen studies, involving a total of 1345 patients and 2182
samples, were finally included. RESULTS: The pooled proportion of APC promoter 1A
methylation was 0.62 (95% CI 0.52-072) and 0.34 (95% CI 0.21-0.50) in cancer
tissues and autologous controls, respectively. The APC gene promoter 1A
methylation rate in cancer tissues was much higher than in autologous controls,
with a pooled OR of 3.66 (95% CI 2.12-6.33). A strong and significant correlation
of APC gene promoter 1A methylation between tumor tissues and autologous controls
was detected (correlation coefficient rpearson = 0.77; P = 0.0013). CONCLUSION:
The proportion of APC promoter 1A methylation in lung cancer tissues was higher
than in autologous controls, indicating that promoter 1A methylation of the APC
gene may play an important role in NSCLC carcinogenesis.
PMID- 28497893
TI - The 4Kscore blood test accurately identifies men with aggressive prostate cancer
prior to prostate biopsy with or without DRE information.
AB - INTRODUCTION: The 4Kscore Test is a prebiopsy blood test that incorporates four
prostate protein biomarkers along with patient clinical information to determine
a man's risk for high-grade, aggressive (Gleason >=7) prostate cancer. However,
some men likely to benefit from the test may be seen in primary care settings
where the digital rectal examination (DRE) information is not always obtained. In
this study, we assessed the clinical validity of the 4Kscore Test when the DRE
information was not included in the algorithm. METHODS: The Prospective 4Kscore
Validation Study enrolled 1012 men scheduled for prostate biopsy across 26
urology practices in the United States. The 4Kscore was calculated for each
patient with and without DRE information. The primary outcome was Gleason >=7
prostate cancer on prostate biopsy. The contribution of DRE to the predictive
accuracy of the test was evaluated by area under the receiver operating curve
(AUC-ROC), risk calibration and clinical consequences. RESULTS: High-grade,
aggressive prostate cancer was found in 231 (23%) of the 1012 patients. Both
versions of the 4Kscore Test, with and without DRE, showed excellent
discrimination (AUC=0.821 with DRE and AUC=0.818 without DRE input) and excellent
calibration. No clinically significant difference was found between the two
versions of the 4Kscore. CONCLUSIONS: The 4Kscore Test algorithm, whether DRE
findings are available or not, performs well in predicting a man's risk of high
grade, aggressive prostate cancer. Patients who are suspected of having
aggressive prostate cancer can safely have their risk better defined by 4Kscore
even if a DRE has not been performed recently.
PMID- 28497894
TI - Sensor-based gait analysis as a simple tool to measure gait in haemophilia
patients.
PMID- 28497895
TI - In the face of pain: The choice of visual cues in pain conditioning matters.
AB - BACKGROUND: Visual cue conditioning is a valuable experimental paradigm to
investigate placebo and nocebo effects in pain. However, little attention has
been paid to the cues themselves and potential variability of effects (their
quantity and quality) stemming from the choice of stimuli. Yet, this seemingly
methodological question has important implications for the interpretation of
experimental findings in terms of their significance for clinical practice.
METHODS: We investigated the effect of heat pain conditioning using different
types of visual cues (abstract images, faces and pseudo-words) in a group of 22
healthy volunteers. We analysed conditioning effects calculated as the difference
in pain ratings to heat stimuli of identical temperature preceded by conditioned
high or low pain cues with (1) subliminal and supraliminal presentation; and (2)
immediately after conditioning and following extinction. Awareness manipulation
and test following indirect, observational extinction allowed us to assess the
strength and robustness of the conditioning effects induced with different cue
types. RESULTS: We observed no differences in conditioning effect magnitudes
between images, faces and words when all stimuli were presented supraliminally.
With subliminal presentation, only face stimuli elicited a significant effect;
equally only face cue-induced effect withstood extinction. CONCLUSIONS: Our
findings indicate that face-related associations to pain might be stronger than
those elicited with other visual cues, as face cues seem to induce stronger
subliminal effects and withstand mild extinction. SIGNIFICANCE: We compared
different types of neutral cues commonly used in conditioning paradigms and found
that faces elicited a stronger, more robust nonconscious effect than abstract
images or pseudo-words.
PMID- 28497896
TI - Self-Assembled Au/CdSe Nanocrystal Clusters for Plasmon-Mediated Photocatalytic
Hydrogen Evolution.
AB - Plasmon-mediated photocatalytic systems generally suffer from poor efficiency due
to weak absorption overlap and thus limited energy transfer between the plasmonic
metal and the semiconductor. Herein, a near-ideal plasmon-mediated photocatalyst
system is developed. Au/CdSe nanocrystal clusters (NCs) are successfully
fabricated through a facile emulsion-based self-assembly approach, containing Au
nanoparticles (NPs) of size 2.8, 4.6, 7.2, or 9.0 nm and CdSe quantum dots (QDs)
of size ~3.3 nm. Under visible-light irradiation, the Au/CdSe NCs with 7.2 nm Au
NPs afford very stable operation and a remarkable H2 -evolution rate of 73 mmol
gCdSe-1 h-1 (10* higher than bare CdSe NCs). Plasmon resonance energy transfer
from the Au NPs to the CdSe QDs, which enhances charge-carrier generation in the
semiconductor and suppresses bulk recombination, is responsible for the
outstanding photocatalytic performance. The approach used here to fabricate the
Au/CdSe NCs is suitable for the construction of other plasmon-mediated
photocatalysts.
PMID- 28497897
TI - Expression profile of heat shock proteins in placental tissues of patients with
preterm prelabor rupture of membranes and spontaneous preterm labor with intact
membranes.
AB - PROBLEM: Investigating the stress response in the central cotyledon zone of
placental tissue in pregnancies with PPROM, PTB, and at term in labor. METHOD OF
STUDY: Gene expression of Hsp27, Hsp60, Hsp70, Hsp90, and HspBP1 was compared
between these particular groups. Correlation between variables including Hsp gene
expression in placental tissue and the gestational age at delivery, WBC count at
admission, and serum levels of CRP at admission in patients with PPROM and PTB
was determined. RESULTS: Both PPROM and PTB pregnancies were associated with
altered Hsp gene expression profile. While PPROM and PTB always induced
upregulation of Hsp27 and Hsp60, downregulation of Hsp70 and HspBP1 was present
entirely in patients with PPROM. HspBP1 expression profile was also able to
differentiate between PPROM and PTB pregnancies. The highest mRNA levels of Hsp60
and Hsp70 were detected in PTB pregnancies with elevated CRP levels at admission.
Some of the examined Hsp displayed increased expression with advancing
gestational age in both groups (PPROM: Hsp27, Hsp70, and Hsp90; and PTB: Hsp27).
CONCLUSION: Upregulation of Hsp27 is a common phenomenon shared between
pregnancies affected with PTB and PPROM. On the other hand, downregulation of
Hsp70 and HspBP1 represents a unique feature of PPROM.
PMID- 28497898
TI - Additional cytogenetic abnormalities and variant t(9;22) at the diagnosis of
childhood chronic myeloid leukemia: The experience of the International Registry
for Chronic Myeloid Leukemia in Children and Adolescents.
AB - BACKGROUND: In the adult population with newly diagnosed chronic myeloid leukemia
(CML), variant translocations are usually not considered to be impairing the
prognosis, whereas some additional cytogenetic abnormalities (ACAs) are
associated with a negative impact on survival. Because of the rarity of CML in
the pediatric population, such abnormalities have not been investigated in a
large group of children with CML. METHODS: The prognostic relevance of variant
t(9;22) and ACAs at diagnosis was assessed in 301 children with CML in the
chronic phase who were enrolled in the International Registry for Chronic Myeloid
Leukemia in Children and Adolescents. RESULTS: Overall, 19 children (6.3%)
presented with additional cytogenetic findings at diagnosis: 5 children (1.7%)
had a variant t(9;22) translocation, 13 children (4.3%) had ACAs, and 1 had both.
At 3 years, for children with a classic translocation, children with ACAs, and
children with a variant t(9;22) translocation who were treated with imatinib as
frontline therapy, the probability of progression-free survival (PFS) was 95%
(95% confidence interval [CI], 91%-97%), 100%, and 75% (95% CI, 13%-96%),
respectively, and the probability of overall survival (OS) was 98% (95% CI, 95%
100%), 100% (95% CI, 43%-98%), and 75% (95% CI, 13%-96%), respectively. No
statistical difference was observed between the patients with classic cytogenetic
findings and those with additional chromosomal abnormalities in terms of PFS and
OS. CONCLUSIONS: In contrast to adults with CML, additional chromosomal
abnormalities observed at diagnosis do not seem to have a significant prognostic
impact. Cancer 2017;123:3609-16. (c) 2017 American Cancer Society.
PMID- 28497900
TI - Utility and reliability of non-invasive muscle function tests in high-fat-fed
mice.
AB - NEW FINDINGS: What is the central question of this study? Non-invasive muscle
function tests have not been validated for use in the study of muscle performance
in high-fat-fed mice. What is the main finding and its importance? This study
shows that grip strength, hang wire and four-limb hanging tests are able to
discriminate the muscle performance between chow-fed and high-fat-fed mice at
different time points, with grip strength being reliable after 5, 10 and 20 weeks
of dietary intervention. Non-invasive tests are commonly used for assessing
muscle function in animal models. The value of these tests in obesity, a
condition where muscle strength is reduced, is unclear. We investigated the
utility of three non-invasive muscle function tests, namely grip strength (GS),
hang wire (HW) and four-limb hanging (FLH), in C57BL/6 mice fed chow (chow group,
n = 48) or a high-fat diet (HFD group, n = 48) for 20 weeks. Muscle function
tests were performed at 5, 10 and 20 weeks. After 10 and 20 weeks, HFD mice had
significantly reduced GS (in newtons; mean +/- SD: 10 weeks chow, 1.89 +/- 0.1
and HFD, 1.79 +/- 0.1; 20 weeks chow, 1.99 +/- 0.1 and HFD, 1.75 +/- 0.1), FLH
[in seconds per gram body weight; median (interquartile range): 10 weeks chow,
2552 (1337-4964) and HFD, 1230 (749-1994); 20 weeks chow, 2048 (765-3864) and
HFD, 1036 (717-1855)] and HW reaches [n; median (interquartile range): 10 weeks
chow, 4 (2-5) and HFD, 2 (1-3); 20 weeks chow, 3 (1-5) and HFD, 1 (0-2)] and
higher falls [n; median (interquartile range): 10 weeks chow, 0 (0-2) and HFD, 3
(1-7); 20 weeks chow, 1 (0-4) and HFD, 8 (5-10)]. Grip strength was reliable in
both dietary groups [intraclass correlation coefficient (ICC) = 0.5-0.8; P <
0.05], whereas FLH showed good reliability in chow (ICC = 0.7; P < 0.05) but not
in HFD mice after 10 weeks (ICC < 0.5). Our data demonstrate that non-invasive
muscle function tests are valuable and reliable tools for assessment of muscle
strength and function in high-fat-fed mice.
PMID- 28497899
TI - Replacing warfarin with a novel oral anticoagulant: Risk of recurrent bleeding
and stroke in patients with warfarin ineligible or failure in patients with
atrial fibrillation (The ROAR study).
AB - BACKGROUND: A significant proportion of patients treated with warfarin for atrial
fibrillation (AF) become warfarin ineligible (WI) due to major bleeding events
(MBE) or systemic thromboembolism (STE). We report a large multicenter real-world
experience of the use of direct oral antagonists (DOACs) in these WI patients.
METHODS: We report the outcomes of 263 WI patients treated with DOACs. The
primary objective was to evaluate clinical outcomes of STE and MBE with DOACs.
Secondary objective was to assess clinical predictors of repeat MBE and STE on
DOACs. RESULTS: Note that 63% (166 of 263) patients had a repeat MBE on DOACs.
Repeat MBE was significantly higher in patients with prior gastrointestinal
bleeding (74.5% vs. 30%, P < 0.0001). Five percent (12 of 263) developed repeat
STE. Higher mean CHA2DS2VASC (6.5 +/- 1.7 vs. 3.3 +/- 1.6 = 0.001) score was
associated with repeat STE. About 34% (57 of 166) of patients had an intervention
to manage repeat MBE. LAAO devices were successfully used in 67% (12 of 18) high
risk patients who underwent major interventions to manage MBE. CONCLUSION: In WI
patients rechallenged with DOACs, a significant proportion developed repeat MBE.
LAAO devices seem reasonable in those patients who undergo major interventions to
manage MBE with cautious and temporary continuation of DOAC.
PMID- 28497901
TI - Risk factors of periodontal disease in Vietnamese patients.
AB - AIM: The aim of the present study was to assess the association of periodontitis
with dental and smoking behaviors, self-perception of oral status, dental
knowledge, and obesity in Vietnamese patients. METHODS: A cross-sectional study
was conducted on 367 adults who first visited the Faculty of Odonto-Stomatology,
University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam. Information on
demographic characteristics, dental and smoking behaviors, self-perception of
oral status, dental knowledge, and nutritional status was investigated by a self
administered questionnaire. Periodontal status, including plaque index, probing
depth, and bleeding on probing, was examined. Multiple logistic regression
analysis was performed to explore risk factors that were associated with
periodontitis after adjusting for confounding factors. RESULTS: Dental and
smoking behaviors, dental knowledge, and nutritional status were all
significantly related to periodontitis. The multiple logistic regression analysis
showed that patients who had risk factors significantly associated with
periodontitis were those who had dental scaling during the past year (odds ratio
[OR]: 2.2), current smokers (OR: 2.47), who received instructions on oral hygiene
(OR=1.73), and those who were overweight/obese (OR: 4.78). CONCLUSION:
Periodontitis was correlated with dental and smoking behaviors, dental knowledge,
and nutritional status in Vietnamese dental patients. Promoting a healthy
lifestyle, reducing tobacco consumption, motivating oral self-care behaviors,
together with normal weight maintenance, are necessary to reduce periodontal
disease burdens.
PMID- 28497902
TI - Size, Shape, and Lateral Correlation of Highly Uniform, Mesoscopic, Self
Assembled Domains of Fluorocarbon-Hydrocarbon Diblocks at the Air/Water
Interface: A GISAXS Study.
AB - The shape and size of self-assembled mesoscopic surface domains of fluorocarbon
hydrocarbon (FnHm) diblocks and the lateral correlation between these domains
were quantitatively determined from grazing incidence small-angle X-ray
scattering (GISAXS). The full calculation of structure and form factors unravels
the influence of fluorocarbon and hydrocarbon block lengths on the diameter and
height of the domains, and provides the inter-domain correlation length. The
diameter of the domains, as determined from the form factor analysis, exhibits a
monotonic increase in response to the systematic lengthening of each block, which
can be attributed to the increase in van der Waals attraction between molecules.
The pair correlation function in real space calculated from the structure factor
implies that the inter-domain correlation can reach a distance that is over 25
times larger than the domain's size. The full calculation of the GISAXS signals
introduced here opens a potential towards the hierarchical design of mesoscale
domains of self-assembled small organic molecules, covering several orders of
magnitude in space.
PMID- 28497903
TI - Semiconducting Nanowire-Based Optoelectronic Fibers.
AB - The recent ability to integrate semiconductor-based optoelectronic
functionalities within thin fibers is opening intriguing opportunities for
flexible electronics and advanced textiles. The scalable integration of high
quality semiconducting devices within functional fibers however remains a
challenge. It is difficult with current strategies to combine high light
absorption, good microstructure and efficient electrical contact. The growth of
semiconducting nanowires is a great tool to control crystal orientation and
ensure a combination of light absorption and charge extraction for efficient
photodetection. Thus far, however, leveraging the attributes of nanowires has
remained seemingly incompatible with fiber materials, geometry, and processing
approaches. Here, the integration of semiconducting nanowire-based devices at the
tip and along the length of polymer fibers is demonstrated for the first time.
The scalable thermal drawing process is combined with a simple sonochemical
treatment to grow nanowires out of electrically addressed amorphous selenium
domains. First principles density-functional theory calculations show that this
approach enables to tailor the surface energy of crystal facets and favors
nanowire growth along a preferred orientation, resulting in fiber-integrated
devices of unprecedented performance. This novel platform is exploited to
demonstrate an all-fiber-integrated fluorescence imaging system, highlighting
novel opportunities in sensing, advanced optical probes, and smart textiles.
PMID- 28497905
TI - Flavanones: Citrus phytochemical with health-promoting properties.
AB - Citrus fruit and juices represent one of the main sources of compounds with a
high potential for health promoting properties. Among these compounds, flavanones
(such as hesperetin, naringenin, eriodictyol, isosakuranetin, and their
respective glycosides), which occur in quantities ranging from ~180 to 740 mg/L
(depending on the Citrus species and cultivar) are responsible for many
biological activities. These compounds support and enhance the body's defenses
against oxidative stress and help the organism in the prevention of
cardiovascular diseases, atherosclerosis, and cancer. Moreover, among other
properties, they also show anti-inflammatory, antiviral, and antimicrobial
activities. This review analyzes the biochemistry, pharmacology, and biology of
Citrus flavanones, emphasizing the occurrence in Citrus fruits and juices and
their bioavailability, structure-function correlations and ability to modulate
signal cascades both in vitro and in vivo. (c) 2017 BioFactors, 43(4):495-506,
2017.
PMID- 28497906
TI - Cytokine profiling analysis following a non-ablative fractional laser on rat
skin.
PMID- 28497907
TI - Effect of TiO2 nanoparticles on some photophysical characteristics of ketocyanine
dyes.
AB - The effect of titanium dioxide (TiO2 ) nanoparticles (NPs) on photophysical
characteristics of 2,5-di[(E)-1-(4-dimethylaminophenyl) methylidine]-1
cyclopentanone (2,5-DMAPMC) and 2,5-di[(E)-1-(4-diethylaminophenyl)methylidine]-1
cyclopentanone (2,5-DEAPMC) ketocyanine dyes has been studied using absorption,
steady-state and time-resolved fluorescence spectroscopy. The magnitudes of
association constants determined based on modified absorption spectrum of dyes
due to the presence of TiO2 NPs indicate the interaction of TiO2 NPs with dye
molecules. The quenching of fluorescence intensity of dyes by TiO2 NPs is
observed and it follows linear Stern-Volmer (S-V) equation. The magnitude of
quenching rate parameter suggests the involvement of static quenching mechanism.
The involvement of electron transfer process in reducing fluorescence intensity
of dyes has been discussed. Also, varying influence of TiO2 NPs on two dyes is
explained based on the presence of different alkyl substituent in two dyes.
PMID- 28497908
TI - The molybdenum cofactor enzyme mARC: Moonlighting or promiscuous enzyme?
AB - Molybdenum (Mo) is present in the active center of eukaryotic enzymes as a
tricyclic pyranopterin chelate compound forming the Mo Cofactor (Moco). Four Moco
containing enzymes are known in eukaryotes, nitrate reductase (NR), sulfite
oxidase (SO), xanthine oxidoreductase (XOR), and aldehyde oxidase (AO). A fifth
Moco enzyme has been recently identified. Because of the ability of this enzyme
to convert by reduction several amidoximes prodrugs into their active amino
forms, it was named mARC (mitochondrial Amidoxime Reducing Component). This
enzyme is also able to catalyze the reduction of a broad range of N-hydroxylated
compounds (NHC) as the base analogue 6-hydroxylaminopurine (HAP), as well as
nitrite to nitric oxide (NO). All the mARC proteins need reducing power that is
supplied by other proteins. The human and plants mARC proteins require a
Cytochrome b5 (Cytb5) and a Cytochrome b5 reductase (Cytb5-R) to form an electron
transfer chain from NADH to the NHC. Recently, plant mARC proteins were shown to
be implicated in the reduction of nitrite to NO, and it was proposed that the
electrons required for the reaction were supplied by NR instead of Cytochrome b5
components. This newly characterized mARC activity was termed NO Forming Nitrite
Reductase (NOFNiR). Moonlighting proteins form a special class of multifunctional
enzymes that can perform more than one function; if the extra function is not
physiologically relevant, they are called promiscuous enzymes. In this review, we
summarize the current knowledge on the mARC protein, and we propose that mARC is
a new moonlighting enzyme. (c) 2017 BioFactors, 43(4):486-494, 2017.
PMID- 28497909
TI - The therapeutic alliance in different mental disorders: A comparison of patients
with depression, somatoform, and eating disorders.
AB - OBJECTIVE: The therapeutic alliance is intensively investigated in psychotherapy
research. However, there is scarce research on the role of the specific diagnosis
of the patient in the formation of the therapeutic alliance. Hence, the aim of
this study was to address this research gap by comparing the alliance in
different mental disorders. DESIGN: Our sample comprised 348 patients (mean age =
40 years; 68% female; 133 patients with depression, 122 patients with somatoform
disorders, and 93 patients with eating disorders). METHODS: Patients completed
the Working Alliance Inventory and measures of therapeutic outcome in early,
middle, and late stages of inpatient psychotherapy. We applied multivariate
multilevel models to address the nested data structure. RESULTS: All three
disorder groups experienced positive alliances that increased across the course
of therapy and showed similar alliance-outcome relations that were of comparable
strengths as in current meta-analyses. However, we found perspective incongruence
of alliance ratings from patient and therapist in the three disorder groups.
CONCLUSIONS: Our results generally indicate that the working alliance is of
importance irrespective of the specific mental disorder. Perspective incongruence
feedback of working alliance experiences could help to strengthen coordination
between patient and therapist and thereby improve the therapeutic process.
Further implications of these findings are discussed. PRACTITIONER POINTS: We
found no differences in the strengths of alliance ratings and alliance-outcome
associations in depressive, somatoform, and eating disorder patients. This
indicates that the working alliance is of general clinical importance
irrespective of the disorder group and should be a central target in all
therapies. We found perspective incongruence in alliance ratings between patient
and therapist in all three disorder groups. Perspective incongruence feedback of
working alliance experiences could help to strengthen coordination between
patient and therapist and thereby improve the therapeutic process.
PMID- 28497911
TI - The Clinical Efficacy of Pollen Extract and Vitamins on Chronic
Prostatitis/Chronic Pelvic Pain Syndrome Is Linked to a Decrease in the Pro
Inflammatory Cytokine Interleukin-8.
AB - PURPOSE: We aim to evaluate the efficacy of pollen extract in association with
vitamins in patients affected by chronic prostatitis/chronic pelvic pain syndrome
(CP/CPPS) and to evaluate the level of the pro-inflammatory mediators interleukin
(IL)-6, IL-8, and IL-10. MATERIALS AND METHODS: Patients diagnosed with CP/CPPS
between January and December 2015 were enrolled in this study. Participants were
randomly assigned to receive oral capsules of pollen extract and vitamins (group
A) or bromelain (group B) for 3 months. At the enrolment time and 3 months after
enrolment, all patients completed questionnaires (the National Institutes of
Health Chronic Prostatitis Symptom Index [NIH-CPSI] and the Short Form-36 and
underwent urological examinations and microbiological evaluation. Levels of IL-6,
IL-8, and IL-10 were evaluated in seminal plasma. RESULTS: Sixty-five male
patients (mean age of 32.7+/-4.7 years) were analysed (group A, n=32; group B,
n=33). At the follow-up examination, 24 of the 32 patients in group A showed a
significant reduction in the NIH-CPSI total score compared with 8 of the 33
patients in the bromelain group (p<0.001). Moreover, the mean level of IL-8 was
significantly lower in the pollen extract and vitamins group when compared with
the bromelain group (298 pg/mL vs. 736 pg/mL, respectively; p<0.001). In group A
we found a statistically significant reduction in the levels of IL-8 between
enrolment and the follow-up visit (878 pg/mL vs. 298 pg/mL, respectively;
p<0.001). CONCLUSIONS: Treatment with pollen extract and vitamins improved the
quality of life in CP/CPPS patients by reducing the levels of pro-inflammatory IL
8.
PMID- 28497912
TI - Testosterone Replacement Therapy: Long-Term Safety and Efficacy.
AB - Recent position statements and guidelines have raised the distinction between a
true and false, age-related hypogonadism (HG) or late-onset hypogonadism (LOH).
The former is the consequence of congenital or acquired "organic" damage of the
brain centers or of the testis. The latter is mainly secondary to age-related
comorbidities and does not require testosterone (T) therapy (TTh). In addition,
concerns related to cardiovascular (CV) safety have further increased the
scepticism related to TTh. In this paper, we reviewed the available evidence
supporting the efficacy of TTh in non-organic HG and its long term safety. A
large amount of evidence has documented that sexual symptoms are the most
specific correlates of T deficiency. TTh is able to improve all aspects of sexual
function independent of the pathogenetic origin of the disease supporting the
scientific demonstration that LOH does exist according to an "ex-juvantibus"
criterion. Although the presence of metabolic derangements could mitigate the
efficacy of TTh on erectile dysfunction, the positive effect of TTh on body
composition and insulin sensitivity might counterbalance the lower efficacy. CV
safety concerns related to TTh are essentially based on a limited number of
observational and randomized controlled trials which present important
methodological flaws. When HG is properly diagnosed and TTh correctly performed
no CV and prostate risk have been documented.
PMID- 28497914
TI - Role of Breast-feeding in the Development of Atopic Dermatitis in Early
Childhood.
PMID- 28497913
TI - Role of Antioxidants in Assisted Reproductive Techniques.
AB - Oxidative stress (OS) has been recognized as a significant cause of suboptimal
assisted reproductive outcome. Many of the sperm preparation and manipulation
procedures that are necessary in the in vitro environment can result in excessive
production of reactive oxygen species (ROS) thereby exposing the gametes and
growing embryos to significant oxidative damage. Antioxidants have long been
utilized in the management of male subfertility as they can counterbalance the
elevated levels of ROS inducing a high state of OS. Few studies have looked into
the clinical effectiveness of antioxidants in patients undergoing assisted
reproduction. While an overall favorable outcome has been perceived, the specific
clinical indication and optimal antioxidant regimen remain unknown. The goal of
our review is to explore the sources of ROS in the in vitro environment and
provide a clinical scenario-based approach to identify the circumstances where
antioxidant supplementation is most beneficial to enhance the outcome of assisted
reproduction.
PMID- 28497915
TI - In Vitro Diagnostic Testing for Antibiotic Allergy.
AB - Allergy to antibiotics is an important worldwide problem, with an estimated
prevalence of up to 10% of the population. Reaction patterns for different
antibiotics have changed in accordance with consumption trends. Most of the
allergic reactions to antibiotics have been reported for betalactams, followed by
quinolones and macrolides and, to a lesser extent, to others, such as
metronidazole clindamycin and sulfonamides. The diagnostic procedure includes a
detailed clinical history, which is not always possible and can be unreliable.
This is usually followed by in vivo, skin, and drug provocation tests. These are
not recommended for severe, potentially lifethreaten reactions or for drugs that
are known to produce a high rate of false positive results. Given the limitations
of in vivo tests, in vitro test can be helpful for diagnosis, despite having
suboptimal sensitivity. The most highly employed techniques for diagnosing
immediate reactions to antibiotics are immunoassays and basophil activation
tests, while lymphocyte transformation tests are more commonly used to diagnose
non-immediate reactions. In this review, we describe different in vitro
techniques employed to diagnose antibiotic allergy.
PMID- 28497917
TI - Does Breast-feeding Relate to Development of Atopic Dermatitis in Young Korean
Children?: Based on the Fourth and Fifth Korea National Health and Nutrition
Examination Survey 2007-2012.
AB - PURPOSE: There have been conflicting reports concerning the relationship between
breast-feeding and the development of atopic dermatitis (AD) in early childhood.
The objective of this study was to investigate the associations between breast
feeding and the risk of AD in early childhood in Korea. METHODS: We combined the
fourth and fifth Korea National Health and Nutrition Examination Survey data
collected from 2007 to 2012 and analyzed 2,015 children at 1 to 3 years old.
Regression analysis was used to determine the association of the following
variables: AD, feeding types, duration of breast-feeding, and others. RESULTS:
The annual prevalence of exclusive breast-feeding and AD decreased. Parents with
allergic diseases preferred breast-feeding and extended duration of feeding
compared with those without. In multiple logistic regression analyses, exclusive
breast-feeding in feeding type I (P=0.070; adjusted odds ratio [OR]=1.990),
exclusive breast-feeding in feeding type II (P=0.095; adjusted OR=1.495) and
breast-feeding duration (P=0.430; adjusted OR=1.013) were not significantly
related to AD. CONCLUSIONS: Breast-feeding was not found to be associated with an
occurrence of AD in young children. Rather, parents with histories of allergic
diseases tended to prefer breast-feeding and extend its duration. To clarify the
role of breast-feeding in the development of AD, a nation-wide prospective study
is needed.
PMID- 28497916
TI - Emerging Endotypes of Chronic Rhinosinusitis and Its Application to Precision
Medicine.
AB - Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disease with various
underlying pathophysiologic mechanisms which translate to endotypes, in contrast
to clinical phenotypes or histological subtypes. Defining endotypes can help
clinicians predict disease prognosis, select subjects suitable for a specific
therapy, and assess risks for comorbid conditions, including asthma. Therefore,
with recent advancement of biologicals in CRS clinical trials, endotyping can be
a breakthrough in treating recalcitrant CRS. CRS is caused by dysregulated
immunologic responses to external stimuli, which induce various inflammatory
mediators from inflammatory cells, including innate lymphoid cells (ILCs) and T
lymphocytes as well as epithelial cells. Thymic stromal lymphopoietin (TSLP),
interleukin (IL)-25, and IL-33, which are mainly secreted by epithelial cells in
response to external stimuli, act on type 2 ILCs and T helper 2 (Th2) cells,
inducing IL-4, IL-5, and IL-13. Local immunoglobulin E (IgE) production is also a
signature event in nasal polyps (NP). These inflammatory mediators are novel
potential therapeutic targets for recalcitrant CRS. This article reviews recent
publications regarding endotypes and endotype-based therapeutic strategies in CRS
and NP.
PMID- 28497919
TI - Accurate Determination of Childhood Food Allergy Prevalence and Correction of
Unnecessary Avoidance.
AB - PURPOSE: Because the true prevalence of food allergy (FA), as based on the
results of an oral food challenge test (OFC), is unknown, it is likely that
children with suspected FA unnecessarily eliminate potentially causative foods.
This study aimed to identify the prevalence of FA and to determine the proportion
of children who unnecessarily eliminate food. METHODS: To identify children with
FA, a primary survey was conducted via a questionnaire with all children aged 0
18 years in Niijima village (remote islands of Japan). In the secondary survey, a
detailed medical interview was conducted by doctors with children who currently
did not eat some foods. The third survey involved serum food-specific
immunoglobulin E (IgE) tests and an OFC for children with suspected FA. RESULTS:
Of 376 enrolled children, 374 (99.5%) completed the questionnaire. Some foods
were eliminated by 18.6% and 13.0% of all children and those >=6 years old,
respectively. The target population for the secondary survey included 69 children
who all completed the medical interview. The target population for the third
survey consisted of 35 children, of whom 26 (74.3%) underwent the blood test. An
OFC was performed 35 times with 20 children. As a result, the prevalence of FA
was 4.9% in children of all ages and 4.7% in those >=6 years old. Moreover, 55.0%
children were able to cease eliminating food intake. CONCLUSIONS: It is possible
that a considerable number of children unnecessarily eliminate food because of
suspected FA.
PMID- 28497918
TI - Allergic Rhinitis in Preschool Children and the Clinical Utility of FeNO.
AB - PURPOSE: The nature of allergic rhinitis (AR) in preschool aged children remains
incompletely characterized. This study aimed to investigate the prevalence of AR
and its associated risk factors in preschool-aged children and to assess the
clinical utility of fractional exhaled nitric oxide (FeNO). METHODS: This general
population-based, cross-sectional survey included 933 preschool-aged (3- to 7
year-old) children from Korea. Current AR was defined as having nasal symptoms
within the last 12 months and physician-diagnosed AR. RESULTS: The prevalence of
current AR in preschool children was 17.0% (156/919). Mold exposure (adjusted
odds ratio [aOR], 1.67; 95% confidence interval [CI], 1.15-2.43) and the use of
antibiotics (aOR, 1.97; 95% CI, 1.33-2.90) during infancy were associated with an
increased risk of current AR, whereas having an older sibling (aOR, 0.52; 95% CI,
0.35-0.75) reduced the risk. Children with current atopic AR had significantly
higher geometric mean levels of FeNO compared to those with non-atopic rhinitis
(12.43; range of 1standard deviation [SD], 7.31-21.14 vs 8.25; range of 1SD, 5.62
12.10, P=0.001) or non-atopic healthy children (8.58; range of 1SD, 5.51-13.38,
P<0.001). The FeNO levels were higher in children with current atopic AR compared
with atopic healthy children (9.78; range of 1SD, 5.97-16.02, P=0.083).
CONCLUSIONS: Mold exposure and use of antibiotics during infancy increases the
risk of current AR, whereas having an older sibling reduces it. Children with
current atopic AR exhibit higher levels of FeNO compared with non-atopic rhinitis
cases, suggesting that FeNO levels may be a useful discriminatory marker for
subtypes of AR in preschool children.
PMID- 28497920
TI - Prevalence of Self-reported Allergic Diseases and IgE Levels: A 2010 KNHANES
Analysis.
AB - PURPOSE: The prevalence of allergic diseases is known to be associated with both
demographic and environmental factors. Herein, we aimed to determine significant
factors associated with the prevalence of allergic diseases and with total
immunoglobulin E (tIgE) and specific immunoglobulin E (sIgE) levels in Korea.
METHODS: We analyzed unweighted data collected by the 2010 Korea National Health
and Nutrition Examination Survey for 2,342 subjects who underwent serum tests for
tIgE and sIgE to Dermatophagoides farinae, dog, and Blattella germanica,
representing a sample of 16,003,645 citizens, by considering the sample weight
and stratification. RESULTS: The overall prevalence of self-reported allergic
diseases was 37.6%. The prevalence rates of allergic rhinitis and atopic
dermatitis decreased with age, whereas the asthma prevalence was not affected by
the age of the subjects. When analyzed according to the type of allergic
diseases, the prevalence of self-reported allergic disease was significantly
associated with various factors (e.g. age, occupation, living in urban areas, and
depression). The tIgE level decreased with age, but later increased. Elevation of
tIgE was significantly associated with male sex, type of occupation, obesity, and
smoking status. However, the risk factors for the increased sIgE levels to each
allergen were quite different. Sensitization to D. farinae was more likely in
young subjects, whereas the prevalence of sensitization to B. germanica was
significantly higher in subjects with male sex, residing in a house (houses), and
with glucose intolerance. Finally, young age and the smoking status were
significantly associated with sensitization to dog. CONCLUSIONS: Various
demographic and environmental factors were significantly associated with the
prevalence of self-reported allergic diseases and the levels of tIgE and sIgE to
D. farinae, B. germanica, and dog in Korea.
PMID- 28497921
TI - Macrolide Resistance and Its Impacts on M. Pneumoniae Pneumonia in Children:
Comparison of Two Recent Epidemics in Korea.
AB - PURPOSE: The aim of this study was to investigate the change in macrolide
resistance rate in pediatric Mycoplasma pneumoniae pneumonia and to evaluate the
influence of macrolide-resistant M. pneumoniae (MRMP) on the clinical course of
disease, by comparing 2 recent, consecutive epidemics in Korea. METHODS: A total
of 250 patients with M. pneumoniae pneumonia admitted to a single tertiary
hospital were enrolled in this study. Detection of MRMP was based on specific
point mutations in domain V of the 23S rRNA gene. The medical records of enrolled
patients were reviewed retrospectively, and the clinical courses and laboratory
data were compared. RESULTS: The macrolide resistance rate of M. pneumoniae was
51.1% (48/94) in the 2011 epidemic, and 87.2% (136/156) in the 2015 epidemic. All
MRMP isolates had the A2063G point mutation. In comparison of 2 epidemics, the
mean age of patients with M. pneumoniae pneumonia was increased, and the total
febrile days and febrile days after initiation of macrolides were prolonged in
the 2015 epidemic. Overall severity of MRMP or macrolide-susceptible M.
pneumoniae (MSMP) pneumonia over 2 epidemics was not significantly changed.
However, the proportion of patients who had a fever lasting more than 72 hours
after initiation of macrolides and who received corticosteroid treatment were
higher in MRMP pneumonia during 2 epidemics. CONCLUSIONS: The macrolide
resistance rate of M. pneumoniae has risen rapidly over 2 recent, consecutive
epidemics, and this has been associated with a prolonged clinical course and
increased use of corticosteroids to treat pediatric M. pneumoniae pneumonia.
PMID- 28497922
TI - Usefulness of In Vivo and In Vitro Diagnostic Tests in the Diagnosis of
Hypersensitivity Reactions to Quinolones and in the Evaluation of Cross
Reactivity: A Comprehensive Study Including the Latest Quinolone Gemifloxacin.
AB - PURPOSE: Reports evaluating diagnosis and cross reactivity of quinolone
hypersensitivity have revealed contradictory results. Furthermore, there are no
reports investigating the cross-reactivity between gemifloxacin (GFX) and the
others. We aimed to detect the usefulness of diagnostic tests of hypersensitivity
reactions to quinolones and to evaluate the cross reactivity between different
quinolones including the latest quinolone GFX. METHODS: We studied 54 patients
(mean age 42.31+/-10.39 years; 47 female) with 57 hypersensitivity reactions due
to different quinolones and 10 nonatopic quinolone tolerable control subjects. A
detailed clinical history, skin test (ST), and single-blind placebo-controlled
drug provocation test (SBPCDPT), as well as basophil activation test (BAT) and
lymphocyte transformation test (LTT) were performed with the culprit and
alternative quinolones including ciprofloxacin (CFX), moxifloxacin (MFX),
levofloxacin (LFX), ofloxacin (OFX), and GFX. RESULTS: The majority (75.9%) of
the patients reported immediate type reactions to various quinolones. The most
common culprit drug was CFX (52.6%) and the most common reaction type was
urticaria (26.3%). A quarter of the patients (24.1%) reacted to SBPCDPTs,
although their STs were negative; while false ST positivity was 3.5% and
ST/SBPCDPTs concordance was only 1.8%. Both BAT and LTT were not found useful in
quinolone hypersensitivity. Cross-reactivity was primarily observed between LFX
and OFX (50.0%), whereas it was the least between MFX and the others, and in GFX
hypersensitive patients the degree of cross-reactivity to the other quinolones
was 16.7%. CONCLUSIONS: These results suggest that STs, BAT, and LTT are not
supportive in the diagnosis of a hypersensitivity reaction to quinolone as well
as in the prediction of cross-reactivity. Drug provocation tests (DPTs) are
necessary to identify both culprit and alternative quinolones.
PMID- 28497923
TI - CCR3 Monoclonal Antibody Inhibits Eosinophilic Inflammation and Mucosal Injury in
a Mouse Model of Eosinophilic Gastroenteritis.
AB - PURPOSE: Although the role of eosinophils in eosinophilic gastroenteritis (EGE)
is not fully understood, they are believed to be a principal effector cell.
Previous studies have demonstrated that eotaxin and its specific receptor,
cysteine-cysteine chemokine receptor-3 (CCR3), play a central role in eosinophil
trafficking into the gastrointestinal (GI) tract. Thus, we examined the targeting
of CCR3 as a potential therapeutic intervention for EGE in a mouse model.
METHODS: Eight- to 10-week-old BALB/c mice were intraperitoneally sensitized and
intragastrically challenged with ovalbumin (OVA). Different groups of mice were
administered either an anti-CCR3 antibody or a control IgG by intraperitoneal
injection 1 hour before each OVA challenge. Eosinophilic inflammation in the
intestinal mucosa, mucosal injury, and severity of diarrhea were compared between
different groups at 1 hour after final OVA challenge. RESULTS: Anti-CCR3 antibody
reduced the number of eosinophils in peripheral blood and intestinal mucosa, but
not in bone marrow. This reduction was associated with restoration of reduced
villous crypt ratio, increased intestinal epithelial cell proliferation, and
weight loss induced by OVA challenge. However, Anti-CCR3 antibody had no effect
on the level of OVA specific immunoglobulin E (IgE) and the expression of
critical chemokines or cytokines in eosinophil trafficking into the GI tract,
such as eotaxin-1, interleukin (IL)-5, and IL-13. CONCLUSIONS: Anti-CCR3 antibody
significantly reduced the severity of eosinophilic inflammation, mucosal injury,
and diarrhea in a mouse model of food allergen-induced GI eosinophilic
inflammation. CCR3 may be a novel therapeutic target for treatment of EGE and
other GI eosinophil-mediated diseases.
PMID- 28497924
TI - Real-life Efficacy of Omalizumab After 9 Years of Follow-up.
AB - Omalizumab is frequently used as add-on treatment to inhaled corticosteroids
(ICS) and long-acting beta2-agonists in patients with suboptimal control of
severe asthma. Patients with severe asthma will typically require chronic
treatment, although due to the limited amount of data available there are still
some concerns about the safety and efficacy of long-term therapy with omalizumab.
Herein, in an extension of a previous 4-year study, we report disease-related
outcomes of 8 patients with severe persistent allergic asthma who have been
followed for a total of 9 years in a real-life setting. Both quality of life
(QoL) (evaluated using the Juniper Asthma-Related QoL Questionnaire [AQLQ]) and
forced expiratory volume in 1 second (FEV1) showed sustained improvement at 9
years. The median values of AQLQ and FEV1 at 4 years were 5.5 and 82.0% compared
to 5.9 and 85.5%, respectively, at 9 years, which were all significantly
increased from baseline. After 9 years, the mean annual number of severe
exacerbations was 0.63 compared to 5 at baseline. There also appeared to be a
trend toward use of a lower dose of ICS at longer follow-up times. After 9 years,
there were no safety concerns for continued use of omalizumab, and no asthma
related hospitalizations or emergency department visits were documented over the
last 5 years. The present analysis is the longest reported clinical follow-up of
omalizumab. Long-term maintenance treatment with omalizumab for up to 9 years is
associated with continued benefits in reducing symptoms, exacerbations, and
medication burden without any safety concerns.
PMID- 28497925
TI - Increased Risk of Chronic Spontaneous Urticaria in Patients With Autoimmune
Thyroid Diseases: A Nationwide, Population-based Study.
AB - There was no previous population-based study on the comparison of the risk of
chronic spontaneous urticaria (CSU) between autoimmune thyroid diseases (AITD)
and age- and gender-matched controls. The primary objective of this study was to
evaluate the risk of CSU after diagnosis of AITD using national registry data
from Korea. The secondary objective was to evaluate other risk factors of CSU.
Based on the disease code diagnoses in 2003-2005, we composed an AITD group
(n=3,659) and an age- and gender-matched control group (n=18,295). Each patient
was tracked for whether CSU occurs or not until 2013. After adjusting for
demographic differences and comorbidities, patients with AITD had a significantly
higher rate of CSU compared to the control group (hazard ratio [HR], 1.46; 95%
confidence interval [CI], 1.25-1.70; P<0.001). Among the AITD patients, the
adjusted HR for CSU was higher in patients with Hashimoto's thyroiditis (HR,
1.50) than in those with Grave's disease (HR, 1.33), although the difference was
not statistically significant (P=0.368). Analysis of CSU patients associated with
AITD showed that female patients had a significantly higher risk of CSU compared
to male ones (HR, 1.34; P=0.001) and that those with allergic rhinitis (HR, 1.51;
P<0.001), atopic dermatitis (HR, 2.44; P<0.001), and asthma (HR, 1.50; P<0.001)
had a significantly higher risk of CSU compared to patients without respective
diseases. Our results demonstrated that AITD could be significantly associated
with an increased risk of CSU.
PMID- 28497926
TI - Plasma LTE4/PGF2alpha Ratio and Blood Eosinophil Count Are Increased in Elderly
Asthmatics With Previous Asthma Exacerbation.
AB - The tools for asthma control assessment recommended by the current guideline are
cognitive function- and effort-dependent, which is substantially impaired in the
elderly. The aim of this study is to investigate objective assessment tools of
asthma control status and previous asthma exacerbation (AE) in elderly subjects.
Asthmatics aged >60 years who were treated with step 2 or 3 by the Global
Initiative for Asthma (GINA) guideline were enrolled. During the 12-week study
period, the subjects used either 400 MUg of budesonide plus 10 mg of montelukast
or 800 MUg of inhaled budesonide. The occurrence of AE during the 4-week run-in
and 12-week treatment period was monitored. After 12-week of treatment, sputum
eosinophil count, peripheral eosinophil count, the plasma leukotriene E4 (LTE4),
and prostaglandin F2alpha (PGF2alpha) metabolite levels were measured using the
UHPLC/Q-ToF MS system. The study subjects were divided into group 1 (asthmatics
who experienced AE during the study period) and group 2 (those who did not). A
total of 101 patients aged 60-85 years were enrolled. Twenty-three patients
(22.8%) had experienced AE. The plasma LTE4 level, LTE4/PGF2alpha ratio, and
peripheral eosinophil count were significantly higher in group 1 than in group 2
(P=0.023, P=0.010, P=0.033, respectively). The plasma LTE4/PGF2alpha ratio and
peripheral eosinophil count at week 12 were significantly associated with
previous AE (odds ratio [OR]=1.748, P=0.013; OR=1.256, P=0.027). Receiver
operating characteristic (ROC) curves to discriminate the subjects with previous
AE, including these 2 parameters, showed that the area under the curve was 0.700
(P=0.004), with 73.9% sensitivity and 47.9% specificity. In conclusion, a
combination of plasma LTE4/PGF2alpha ratio and peripheral eosinophil count can be
an objective assessment tool which is significantly associated with asthma
control status in elderly asthmatics.
PMID- 28497927
TI - The potential role of pain-related SSEPs in the early prognostication of long
term functional outcome in post-anoxic coma.
AB - BACKGROUND: Cardiac arrest (CA) is a common cause of disability. Multimodal
evaluation has improved prognosis but precocious biomarkers are not appropriate
in determining long-term functional outcome. AIM: To identify early
prognostication markers of long-term functional outcome in post-anoxic coma.
DESIGN: Retrospective assessment of outcomes. POPULATION: Individuals older than
18 years with post-anoxic coma hospitalized in intensive care units after cardiac
arrest (CA) regardless of cause (cardiac or non-cardiac) and location of event
(in or out-of-hospital). METHODS: Clinical, biological and neurophysiological
data were collected within 48 hours from CA. Clinical data included time of no
and low flow, CA rhythm, pupillary reflex, Glasgow motor score at admission and
hyperthermia. Biological marker was the highest creatinine level.
Neurophysiological parameters included EEG pattern and reactivity, Somatosensory
Evoked Potential (SSEP), and Middle-Latency (ML) SSEP evoked at low (10 mA) and
high (50 mA) intensity stimulation. Level of Cognitive Functioning Scale (LCFS),
Disability Rating Scale and recovery from coma (Revised coma Recovery Scale [CRS
R]) were collected at 12 months. A LASSO multiple regression analysis was fitted
to data to investigate the best predictors of LCF, DRS and CRS-R. In-sample
prediction was obtained to verify the quality of fitting, and accuracy indices
(i.e., total error rate) produced. RESULTS: Presence of short and medium latency
SSEPs with low and high stimulation intensity were identified as prognostic
predictors of outcome for all the scales. Error rate was 4.5% for CRS and LCF,
and 9.1% for DRS. CONCLUSIONS: Middle latency somatosensory evoked potentials
associated with short latency somatosensory evoked potentials during the first 48
hours after a cardiac arrest are strong predictors of functional outcome at 12
months from the event. Replication on larger cohorts is needed to support their
routine use as prognostic markers. CLINICAL REHABILITATION IMPACT: These markers
could inform more appropriate allocation of resources, provide a basis for
realistic goal-setting, and help the family to adjust its expectations.
PMID- 28497928
TI - Effects of dual- and complex-task on walking ability of ambulatory individuals
with spinal cord injury.
AB - BACKGROUND: Attempting to perform dual- and complex-tasks obviously reduces the
walking ability of individuals with impaired cognitive functions. However, there
is no clear evidence describing the effects of dual- and complex-tasks on the
walking ability of ambulatory individuals with a spinal cord injury (SCI) who
have intact cognitive functions, but suffer from various degrees of sensorimotor
deterioration. AIM: To primarily investigate the effects of dual- and complex
task on the walking ability of ambulatory subjects with SCI as compared to
healthy individuals. In addition, the study secondarily compared the effects in
subgroups of subjects with SCI, including different age groups, lesion severity
and level of ability. DESIGN: Cross-sectional design. SETTING: A major tertiary
referral and community hospitals in Thailand. POPULATION: Thirty-seven ambulatory
individuals with SCI and 13 healthy subjects. METHODS: All subjects were
evaluated for outcomes while they walked under four conditions, including single
task overground walking (ST-OG), dual-task overground walking (DT-OG) using a
color word Stroop task, single-task obstacle crossing (ST-OC) and dual-task
obstacle crossing (DT-OC). The outcomes were compared among the conditions and
between the groups of subjects in terms of walking time, obstacle crossing
ability and percent of Stroop task errors. RESULTS: With the increasing
complexity of the tasks, both SCI and healthy subjects walked significantly
slower (P<0.001 for those with SCI and P<0.05 for healthy subjects), but not when
compared between the ST-OC and DT-OG conditions (P>0.05). Subjects also showed a
greater percentage of cognitive task errors when they encountered a dual- and
complex-task, particularly those with SCI who were over 50 years old, had mild
lesion severity or walked with a walking device (P<0.001). CONCLUSIONS: The
incorporation of dual- and complex-task challenged cognitive-motor interference
of ambulatory individuals with SCI. CLINICAL REHABILITATION IMPACT: The
application of such tasks may benefit rehabilitation outcomes in a real-world
situation for patients, especially for those who are older than 50, have mild
lesion severity or use a walking device.
PMID- 28497929
TI - Measurement properties of the Swedish modified version of the Postural Assessment
Scale for Stroke Patients (SwePASS) using Rasch analysis.
AB - BACKGROUND: A previous small-sample (N.=150) Rasch analysis of the Swedish
modified version of the Postural Assessment Scale for Stroke Patients (SwePASS)
suggested problems regarding response categories and redundant items that need
confirmation in larger samples with more severe strokes. AIM: The aim of this
study was to evaluate the measurement properties of the SwePASS in patients with
acute stroke. DESIGN: A multicenter, cross-sectional study. SETTING: Two stroke
units in Western Sweden. POPULATION: The study cohort included 250 consecutive
inpatients undergoing rehabilitation after acute stroke. METHODS: The SwePASS
assessments were performed once within the first four days after admission to the
stroke units. The data were analyzed according to the Rasch measurement model
regarding targeting, model fit, reliability, response category function, local
dependence and differential item functioning. RESULTS: Postural control of 250
patients (median age, 76.5 years) was assessed with the SwePASS within median of
two days after admission to the stroke units. The SwePASS covered a continuum of
different levels of postural control, but had suboptimal targeting with
insufficient representation of lower and higher levels of postural control. The
reliability was high, the item fit statistics were generally acceptable and there
was no differential item functioning by sex, age and stroke localization.
However, response categories did not function as expected for four of the 12
SwePASS items and five items exhibited local dependency. CONCLUSIONS: The SwePASS
exhibited several promising measurement properties. To improve the scale, poor
targeting, illogical response categories and local dependency should be
addressed. CLINICAL REHABILITATION IMPACT: The SwePASS provides valuable clinical
information regarding postural control in the acute phase after stroke.
PMID- 28497930
TI - Mirror therapy for involuntary movement due to chronic thalamic hemorrhage: a
case report.
AB - BACKGROUND: Some stroke survivors suffer from involuntary movement, which often
disturbs upper-limb function, but there are few effective modality options. CASE
REPORT: A 70-year-old man presented with persisting right-upper-limb hemiballism
due to left thalamic hemorrhage ten years before. We provided inpatient
rehabilitation, including repetitive-facilitative exercise and task-related
training, and prescribed clonazepam from day 5 after admission. However, the
affected upper limb showed no significant change and remained nonfunctional. When
we introduced mirror therapy (MT) to the rehabilitation program on day 14,
hemiballism immediately decreased during the MT session, so we added daily MT
sessions of 20 min/day. At discharge on day 42, he was able to use his right hand
for eating meals and folding laundry. CLINICAL REHABILITATION IMPACT: This shows
that MT may have the potential to be a novel therapeutic method for treating
involuntary movement. Further research is needed to elucidate mechanisms by which
MT may reduce hemiballism.
PMID- 28497931
TI - Is outpatient continuous regional analgesia more effective and equally safe than
single-shot peripheral nerve blocks after ambulatory orthopedic surgery?
AB - INTRODUCTION: Continuous regional analgesia is an established technique for
effective postoperative pain treatment, particularly after orthopedic surgical
procedures. Even if it has been increasingly applied to the outpatient setting as
well, many anesthesiologists are still reluctant to discharge patients with a
perineural catheter in place. Aim of this review was to clarify the evidences
about safety and effectiveness of outpatient continuous peripheral nerve blocks.
EVIDENCE ACQUISITION: A systematic review of all prospective, randomized, double
blinded, placebo-controlled trials of the last 20 years on outpatient continuous
peripheral nerve blocks after ambulatory orthopedic surgery was performed, using
both PubMed and OVID databases were. Study quality was assessed using the
modified Jadad Scale. Primary outcomes were pain at 24 and 48 hours and morphine
consumption. EVIDENCE SYNTHESIS: Five studies matched the inclusion criteria and
were considered of good quality to be included in the review process. All these
studies consistently showed a better pain control both at rest and during
movement within the first postoperative day, leading to a reduced opioid
consumption in patients treated with outpatient continuous regional analgesia.
However, only three studies showed these advantages to be sustained longer than
the first 24 hours postoperatively. No severe complications were reported.
CONCLUSIONS: High-quality evidences about outpatient regional analgesia are
scarce. Considering the advantages of continuous peripheral nerve blocks in the
inpatient setting more prospective studies assessing also functional recovery are
needed to further implement these techniques in the ambulatory setting.
PMID- 28497932
TI - Individual duration of axillary brachial plexus block is unpredictable: a
prospective double centered observational study.
AB - BACKGROUND: The duration of effect for axillary plexus block using ropivacaine is
highly variable. The available literature does not offer any plausible means of
predicting time of block offset for individual patients, making it difficult to
give accurate information and plan postoperative analgesics. This study was
designed to identify factors influencing axillary plexus block offset time.
METHODS: A total of 92 patients participated in this prospective double centred
observational study. All patients were scheduled for axillary plexus block with
ropivacaine 0.75% and subsequent block duration was recorded. RESULTS: Mean time
of axillary plexus block offset was 13.5 hours, with a range of 4.8 to 25.4
hours. No statistical significant differences in offset time was seen with regard
to gender, age, body weight, BMI and ASA-classification. A trend for increasing
duration of blocks associated with increasing age was observed. No statistically
significant difference was identified in block duration between blocks performed
with nerve stimulator guidance versus ultrasound guidance. Similarly, neither
dose nor volume of ropivacaine 0.75% was identified as a factor influencing block
duration. CONCLUSIONS: This prospective study demonstrates a large inter
individual variation in time of axillary plexus block offset using ropivacaine
0.75%. The lack of association between offset time and both demographic and block
performance factors, makes predictability of individual duration of axillary
plexus blocks in clinical practice extremely difficult. We suggest that all
patients should be made aware of such variability in duration prior to block
placement.
PMID- 28497933
TI - Scalp block for glioblastoma surgery is associated with lower inflammatory scores
and improved survival.
AB - BACKGROUND: Regional anesthesia has anti-inflammatory effects. Recent studies
suggest that regional anesthesia might improve the survival of patients with
cancer. We hypothesized that the use of a scalp block (SB) during craniotomy for
glioblastoma (GB) decreases the postoperative systemic and local inflammatory
response and extend their survival. METHODS: This retrospective study included
119 patients with GB who underwent tumor resection. We divided patients into 2
groups based on the use of SB during surgery. Preoperative and postoperative
neutrophil-to-lymphocyte (NLR) ratio and platelet-to-lymphocyte (PLR) ratios were
calculated as well as the percentage change in postoperative T2/FLAIR (FLuid
Attenuated Inversion Recovery) volume. Both markers of the inflammatory response
were compared between patients with and without an SB. Progression-free survival
(PFS) was also compared in both groups of patients. Univariate and multivariate
analysis were used to test the association between SB and patients' survival.
RESULTS: On day 3 after surgery, patients who had an SB showed statistically
significant lower NLRs and PLRs than those without an SB. There was also a
significant larger reduction in postoperative T2/FLAIR signal in patients with SB
than in those without SB. The median PFS (progression-free survival) was longer
in patients with SB (16.7 months) than those without an SB (6.5 months, P<0.001).
The multivariate analysis indicated that the use of SB was an independent factor
for longer PFS (hazard ratio: 0.31 95% confidence interval: 0.07-0.21, P<0.001).
CONCLUSIONS: This retrospective study supports the hypothesis that in patients
with GB undergoing craniotomy, the use of SB is associated with lower levels of
systemic and local inflammation, and longer survival.
PMID- 28497934
TI - Cerebral autoregulation monitoring in acute traumatic brain injury: what's the
evidence?
AB - Cerebral autoregulation is conceptualized as a vascular self-regulatory mechanism
within the brain. Controlled by elusive relationships between various biophysical
processes, it functions to protect the brain against potential damages caused by
sudden changes in cerebral perfusion pressures and flow. Following events such as
traumatic brain injuries (TBI), autoregulation may be compromised, potentially
leading to an unfavorable outcome. In spite of its complexity, autoregulation has
been able to be quantified non-invasively within the neuro-critical care setting
with the aid of transcranial Doppler. This information is interpreted
particularly through calculated derived indices based on commonly-monitored input
signals such as arterial blood pressure and intracranial pressure (i.e. Pressure
Reactivity Index [PRx], Mean Flow Index, etc.). For example, PRx values that
trend towards positive numbers are correlated with unfavorable outcome. These
predictors are primarily surrogate markers of cerebral hemodynamic activity,
although suggesting robust correlations between these indices and patient
outcome. This review of the literature seeks to explain the methodology behind
the calculations of various measures of autoregulation in adult patients
suffering from traumatic brain injuries, and how they can interact with one
another to both create larger effects on patient outcome and general outcome
prediction models. Insight into the driving forces behind cerebral autoregulation
is imperative for guiding both clinical decision-making and global treatment
protocols for neuro-critically ill patients. The evidence that autoregulation
oriented therapy may improve outcome after TBI is still oscillating around Level
III.
PMID- 28497935
TI - The LMA-Flexible: time to celebrate a unique extraglottic airway device.
PMID- 28497936
TI - Grading health claims by weight of evidence would make for a better-informed
public.
AB - In the European Regulation 1924/2006 and especially its first recital, the
evaluation of health claims (HC) by European Food Safety Agency (EFSA) was
introduced so as "to ensure a high level of consumer protection, [and] give the
consumer the necessary information to make choices in full knowledge of the
facts...". Now, with 10 years of hindsight since the Regulation was adopted, it
can be asked whether EFSA HC process of evaluation that led to a marginal number
of accepted claims is consistent with this objective, not just for protecting
consumers but for allowing them to decide freely and make informed choices. The
aim of this paper was to demonstrate that the inclusion of a ranking of the
weight of evidence in the assessment of EFSA's scientific substantiation of HC
would allow consumers to benefit from the very high standard of scientific
evaluation performed by EFSA. The definition of standards of proof is a
generalized practice and rests on the principle that evaluations of health
practices should be understood in terms of descriptions ranging from formal proof
from high-power double-blind placebo-controlled studies to rankings based on the
consensus views of experts or even agreement among professionals. Grading of
weight of evidence - not of scientific expertise - is pervasive in all the
recommendations or consensus meetings of health authorities or learned societies.
This approach would stimulate research and product innovation as industrials
would see a positive return on investment.
PMID- 28497937
TI - Cone-beam volumetric imaging in craniofacial medicine.
AB - With the development of x-ray computed tomography (CT) in the 1960s and its first
use for clinical studies in 1972 by Sir Godfrey Hounsfield, radiological
tomography attained widespread use and today is one of the essential imaging
techniques in medical radiology. It is a technically mature and clinically widely
accepted method and complements classical x-ray panoramic radiography in many
areas. The technology is frequently used in craniofacial radiology, because of
its characteristic low radiation dose, high spatial resolution and lower cost
compared with CT. The aim of this work is to: describe the principles of Cone
beam computed tomography (CBCT), to make a brief description of the existing
devices, to present briefly the use of 3D diagnosis in craniofacial medicine.
PMID- 28497938
TI - Cardiovascular consequences of hypophosphatemia.
AB - INTRODUCTION: Few studies have been conducted to evaluate the effect of
hypophosphatemia on cardiovascular consequences. The goal of this review was to
determine whether hypophosphatemia is associated with cardiovascular consequences
and to increase its awareness as a new clinical entity and a reversible cause of
cardiovascular consequences. EVIDENCE ACQUISITION: We searched MEDLINE and PubMed
through September 2016 for primary studies that reported the relationship between
hypophosphatemia and cardiovascular consequences including cardiomyopathy and
arrhythmia. EVIDENCE SYNTHESIS: A total of 937 articles were initially obtained.
Of these articles, 921 publications were excluded according to the inclusion and
exclusion criteria. Sixteen articles were included in this review. These articles
included 3 prospective cohort studies, 1 retrospective cohort study, 7 case
series or case reports, 2 case-control studies, 1 pre- vs. post-test in a single
group, and 2 animal studies. CONCLUSIONS: The mechanisms of hypophosphatemia in
cardiomyopathy and arrhythmia have been reported to be a depletion of adenosine
triphosphate in myocardial cells and decreased 2,3-diphosphoglycerate in
erythrocytes. Left ventricular performance seems to improve when severe
hypophosphatemia is corrected, but not in those with mild to moderate
hypophosphatemia. However, analyses of the relationship between cardiac function
and hypophosphatemia using clinical end points have not been conducted. The
association between hypophosphatemia and arrhythmia remains unclear, but
anecdotal reports exist in the literature.
PMID- 28497939
TI - Role for imaging in spondyloarthritis.
AB - INTRODUCTION: Despite major progress in the imaging diagnosis of
spondyloarthritis (SpA), the relative advantages of various available imaging
techniques remain unclear. The aim of this study is to assess the current use of
imaging in the diagnosis of SpA and to provide suitable recommendations for the
use of imaging as an outcome measure as defined in the Assessment in
SpondyloArthritis international Society (ASAS) criteria. EVIDENCE ACQUISITION: A
systematic literature search regarding imaging in SpA was performed. Articles
were assessed by two reviewers to identify and summarized key information
pertaining to imaging in SpA. EVIDENCE SYNTHESIS: The search identified 180
relevant articles. Conventional radiography (CR) (17 articles), ultrasound (US)
(26 articles), conventional computed tomography (CT) (13 articles), spectral
computed tomography (spectral CT) (2 articles), bone scintigraphy (24 articles),
and magnetic resonance imaging (MRI) were assessed (98 articles). Sacroiliitis
and enthesitis were the major imaging findings in SpA. Multiple studies assessed
the feasibility, validity, or differences among imaging modalities for the
diagnosis of SpA; however, comprehensive assessments were not available due to a
paucity of prospective imaging studies. CR is a widely available, inexpensive
initial approach to evaluate patients with suspected SpA. CT enables assessment
of structural changes from chronic sacroiliitis including bony erosions,
subchondral sclerosis, joint space narrowing, and ankyloses; however, both CR and
CT modalities are insensitive for demonstrating early enthesitis and sacroiliitis
in SpA. US mainly identifies appendicular enthesitis but is more limited with
respect to the sacroiliac joints. Bone scintigraphy can identify sacroiliac joint
lesions and semi-quantitatively assess active sacroiliitis. MRI optimally
evaluates not only early enthesitis and sacroiliitis of SpA but also chronic
structural changes to the sacroiliac joints. CONCLUSIONS: More than one modality
may be required for diagnostic and assessment of SpA depending upon disease
characteristics and evolution. CR is a suitable initial examination while MRI is
able to detect both early and late changes of SpA. A combination of CR and MRI is
recommended for the diagnosis and assessment of SpA.
PMID- 28497940
TI - Evaluation of diabetic foot infection in nuclear medicine.
AB - Diabetic foot infection is not only the most common cause of hospitalization
among diabetic patients, but is also associated with high morbidity, mortality
and major utilization of the resources. Managing diabetic patients with suspected
foot infection is highly dependent on an early and accurate determination of its
presence and location. Medical imaging is often used in the workup of these
patients, as clinical diagnosis of osteomyelitis is often difficult, and invasive
bone biopsy is infrequently used due to many limitations. In this article, we
review the role and accuracy of commonly used medical imaging modalities in the
evaluation of diabetic patients with suspected foot infection including
osteomyelitis with particular emphasis on molecular nuclear medicine imaging. The
impact of imaging on patients' management is also discussed. We finally comment
on possible future directions in hybrid molecular imaging techniques.
PMID- 28497941
TI - Antiarrhythmic effects of ranolazine used both alone for prevention of atrial
fibrillation and as an add-on to intravenous amiodarone for its pharmacological
cardioversion: a meta-analysis.
AB - INTRODUCTION: Recent evidence from relatively small randomized controlled trials
would seem to support a useful role of ranolazine for the prevention and
treatment of atrial fibrillation (AF). The present study is aimed at providing
information about the possible beneficial anti-arrhythmic properties of
ranolazine. In particular, the meta-analysis carried out in this study focuses on
the application of ranolazine to prophylaxis and treatment of atrial
fibrillation. EVIDENCE ACQUISITION: Both methods randomized controlled trials
(RCTs) and non-randomized observational studies concerning the effects of
ranolazine on AF were included in the meta-analysis. In each of the considered
studies, a comparison was made between a group of patients taking ranolazine and
a second group treated instead with another antiarrhythmic therapy, or assigned
to placebo. Efficacy outcomes were the risk of new-onset AF, the probability of
conversion to sinus rhythm of patients with recent occurrence (<=48 h) of AF and
the time to conversion to sinus rhythm. Safety endpoints were death, adverse
events, QTc prolongation and hypotension. EVIDENCE SYNTHESIS: Ten studies (8 RCTs
and 2 nonrandomized observational studies) were gathered on the whole. Ranolazine
was effective in preventing the occurrence of AF when compared to controls
(RR=0.60; 95% CI: 0.43-0.83; P=0.002). Subgroup analysis showed a more pronounced
preventive effect of ranolazine against AF in the postoperative setting of
coronary artery bypass grafting (CABG) surgery (RR=0.39; 95% CI: 0.18-0.83;
P=0.02) when compared to non-postoperative AF (RR=0.76; 95% CI: 0.63-0.92;
P=0.04). Ranolazine enhanced the chances of successful cardioversion when added
to intravenous amiodarone compared to amiodarone alone (RR 1.18; 95% CI: 1.05
1.33; P=0.004) and significantly decreased the time to cardioversion (SMD= -10.35
h; 95% CI: -18.13 hours to -2.57 hours; P<0.001). Overall risks of death, adverse
events, and QTc prolongation were shown to be similar in the comparison between
patients treated with ranolazine and controls. CONCLUSIONS: Ranolazine given
orally at appropriate doses showed the property to significantly quicken the
conversion of AF to sinus rhythm when combined with the IV amiodarone, compared
to IV amiodarone alone. Furthermore, in patients in sinus rhythm, ranolazine
proved to reduce the frequency of new onset AF as well as of its recurrences,
especially in patients undergone CABG surgery, known to be at high risk of
developing postoperative AF. In addition, ranolazine use seems to be safe and
associated with relatively few adverse events.
PMID- 28497942
TI - Effect of combined resistance and endurance exercise training on regional fat
loss.
AB - BACKGROUND: The present study tested the possibility of a localized fat mass (FM)
reduction by means of training programmes focusing on specific bodily regions.
METHODS: Sixteen physically inactive women (age: 31+/-4; BMI: 27.5+/-2.1),
randomly allocated to two groups, completed an 8 week training programme. In one
group (UpBdResist) training sessions consisted of upper body resistance exercises
followed by 30-minute cycling at 50%VO2max, while the other group (LwBdResist)
performed lower body resistance exercises followed by 30 minutes on an arm
ergometer. Regional body composition was assessed by DEXA and skin fold measures.
RESULTS: Regardless of a similar reduction in both groups, UpBdResist training
elicited a greater reduction of the upper limbs (UL) FM as compared to the lower
limbs (LL) (Delta% UL vs. LL: -12.1+/-3.4 vs. -4.0+/-4.7; P=0.02). Conversely, in
the LwBdResist group, FM loss was more pronounced in the LL as compared to the UL
(Delta% UL vs. LL: -2.3+/-7.0 vs. -11.5+/-8.2, P=0.02). Likewise, LwBdResist
elicited a larger effect on lean mass (LM) of the LL as compared to UL (Delta% LL
vs. UL: +8.4+/-5.8 vs. -2.7+/-5.0, P<0.01), yet no differences between upper and
lower limb LM changes were detected in UpBdResist group. CONCLUSIONS: The present
data suggest that a training programme entailing localized explosive resistance
exercise, prior to an endurance exercise bout, may target specific adipose tissue
sites eliciting localised fat mass loss in the upper and lower limbs.
PMID- 28497943
TI - The effects of over-the-counter jaw-repositioning mouthguards on aerobic
performance.
AB - BACKGROUND: Though jaw-repositioning devices have been found to increase size of
upper respiratory airways in individuals, the effects of jaw-repositioning
mouthguards on respiratory function during exercise have not been fully explored.
The purpose of this study is to determine the effects of over-the-counter (OTC)
jaw-repositioning mouthguards on respiratory function and aerobic performance in
male athletes. METHODS: College-aged, male athletes (N.=20) participated in this
randomized, crossover, controlled study. Each subject completed one testing
session per condition: a no mouthguard control (CON), a placebo mouthguard (PLA),
an OTC self-adapted jaw-repositioning mouthguard (SA), and an OTC custom-fitted
jaw-repositioning mouthguard (CF). Each testing session consisted of respiratory
flow dynamic tests at rest. Ventilation and gas exchange were assessed during a
graded maximal treadmill test. Peak blood lactate values were obtained from 0-10
min post-exercise. RESULTS: At rest, the CON had significantly higher peak
expiratory flow rate values than the other conditions (P<0.03). Maximum voluntary
ventilation values for PLA and SA were significantly lower compared to CON
(P<0.02) at rest. No significant differences were observed between conditions for
ventilation, oxygen consumption, or carbon dioxide production during any
submaximal stage (P=0.81) nor at maximal aerobic capacity (P=0.35). Peak lactate
and adjusted peak lactate values were not significantly different between
conditions (P=0.30 and P=0.63, respectively). CONCLUSIONS: The OTC jaw
repositioning mouthguards in this study did not enhance aerobic performance. It
is important to acknowledge that negative effects on aerobic performance were not
observed, thus providing additional support for encouraging the use of this
safety device in sports.
PMID- 28497944
TI - Schedules of Controlled Substances: Temporary Placement of 4-Fluoroisobutyryl
Fentanyl into Schedule I. Temporary scheduling order.
AB - The Administrator of the Drug Enforcement Administration is issuing this
temporary scheduling order to schedule the synthetic opioid, N-(4-fluorophenyl)-N
(1-phenethylpiperidin-4-yl)isobutyramide (4-fluoroisobutyryl fentanyl or para
fluoroisobutyryl fentanyl), and its isomers, esters, ethers, salts and salts of
isomers, esters, and ethers, into schedule I pursuant to the temporary scheduling
provisions of the Controlled Substances Act. This action is based on a finding by
the Administrator that the placement of 4-fluoroisobutyryl fentanyl into schedule
I of the Controlled Substances Act is necessary to avoid an imminent hazard to
the public safety. As a result of this order, the regulatory controls and
administrative, civil, and criminal sanctions applicable to schedule I controlled
substances will be imposed on persons who handle (manufacture, distribute,
reverse distribute, import, export, engage in research, conduct instructional
activities or chemical analysis, or possess), or propose to handle, 4
fluoroisobutyryl fentanyl.
PMID- 28497945
TI - Clarification of Employer's Continuing Obligation To Make and Maintain an
Accurate Record of Each Recordable Injury and Illness. Final rule.
AB - Under the Congressional Review Act, Congress has passed, and the President has
signed, Public Law 115-21, a resolution of disapproval of OSHA's final rule
titled, "Clarification of Employer's Continuing Obligation to Make and Maintain
an Accurate Record of each Recordable Injury and Illness." OSHA published the
rule, which contained various amendments to OSHA's recordkeeping regulations, on
December 19, 2016. The amendments became effective on January 18, 2017. Because
Public Law 115-21 invalidates the amendments to OSHA's recordkeeping regulations
contained in the rule promulgated on December 19, 2016, OSHA is hereby removing
those amendments from the Code of Federal Regulations.
PMID- 28497946
TI - Nanopillar Surface Topology Promotes Cardiomyocyte Differentiation through
Cofilin-Mediated Cytoskeleton Rearrangement.
AB - Nanoscaled surface patterning is an emerging potential method of directing the
fate of stem cells. We adopted nanoscaled pillar gradient patterned cell culture
plates with three diameter gradients [280-360 (GP 280/360), 200-280 (GP 200/280),
and 120-200 nm (GP 120/200)] and investigated their cell fate-modifying effect on
multipotent fetal liver kinase 1-positive mesodermal precursor cells (Flk1+ MPCs)
derived from embryonic stem cells. We observed increased cell proliferation and
colony formation of the Flk1+ MPCs on the nanopattern plates. Interestingly, the
200-280 nm-sized (GP 200/280) pillar surface dramatically increased cardiomyocyte
differentiation and expression of the early cardiac marker gene Mesp1. The
gradient nanopattern surface-induced cardiomyocytes had cardiac sarcomeres with
mature cardiac gene expression. We observed Vinculin and p-Cofilin-mediated
cytoskeleton reorganization during this process. In summary, the gradient
nanopattern surface with 200-280 nm-sized pillars enhanced cardiomyocyte
differentiation in Flk1+ MPCs.
PMID- 28497947
TI - Energy Transfer Kinetics in Photosynthesis as an Inspiration for Improving
Organic Solar Cells.
AB - Clues to designing highly efficient organic solar cells may lie in understanding
the architecture of light-harvesting systems and exciton energy transfer (EET)
processes in very efficient photosynthetic organisms. Here, we compare the
kinetics of excitation energy tunnelling from the intact phycobilisome (PBS)
light-harvesting antenna system to the reaction center in photosystem II in
intact cells of the cyanobacterium Acaryochloris marina with the charge transfer
after conversion of photons into photocurrent in vertically aligned carbon
nanotube (va-CNT) organic solar cells with poly(3-hexyl)thiophene (P3HT) as the
pigment. We find that the kinetics in electron hole creation following excitation
at 600 nm in both PBS and va-CNT solar cells to be 450 and 500 fs, respectively.
The EET process has a 3 and 14 ps pathway in the PBS, while in va-CNT solar cell
devices, the charge trapping in the CNT takes 11 and 258 ps. We show that the
main hindrance to efficiency of va-CNT organic solar cells is the slow migration
of the charges after exciton formation.
PMID- 28497948
TI - In Situ Visualized Cathode Electrolyte Interphase on LiCoO2 in High Voltage
Cycling.
AB - Charging lithium ion battery cathode materials such as LiCoO2 to a higher voltage
may simultaneously enhance the specific capacity and average operating voltage
and thus improve the energy density. However, battery cycle life is compromised
in high voltage cycling due to lattice instability and undesired oxidation of
electrolyte. Cathode solid-electrolyte interphase (SEI), or cathode-electrolyte
interphase (CEI), in situ formed at the cathode-electrolyte interface under high
voltage, is critically important in understanding the cathode degradation process
and crucial in improving high voltage cycle stability. Here we present in situ
atomic force microscopy (AFM) investigation of CEI on LiCoO2 at high voltage. The
formation of CEI is only observed at the LiCoO2 edge plane, not at the basal
plane. The thin layer of Al2O3 coating completely suppresses the formation of CEI
at the edge planes, and is shown to significantly improve coin cell high voltage
cycle stability.
PMID- 28497949
TI - Addition of Lithium 8-Quinolate into Polyethylenimine Electron-Injection Layer in
OLEDs: Not Only Reducing Driving Voltage but Also Improving Device Lifetime.
AB - Solution-processed electron injection layers (EILs) comprising lithium 8
quinolate (Liq) and polyethylenimine ethoxylated (PEIE) are highly effective for
enhancing electron injection from ZnO to organic layers and improving device
lifetime in organic light-emitting devices (OLEDs). Doping of Liq into PEIE
further reduces the work function of zinc oxide (ZnO) by enhancing dipole
formation. The intermolecular interaction between Liq and PEIE was elucidated by
UV-vis absorption measurement and quantum chemical calculation. The OLEDs with
ZnO covered with PEIE:Liq mixture exhibited lower driving voltage than that of
the device without Liq. Furthermore, as doping concentration of Liq into PEIE
increased, the device lifetime and voltage stability during constant current
operation was successively improved.
PMID- 28497951
TI - Garnet Solid Electrolyte Protected Li-Metal Batteries.
AB - Garnet-type solid state electrolyte (SSE) is a promising candidate for high
performance lithium (Li)-metal batteries due to its good stability and high ionic
conductivity. One of the main challenges for garnet solid state batteries is the
poor solid-solid contact between the garnet and electrodes, which results in high
interfacial resistance, large polarizations, and low efficiencies in batteries.
To address this challenge, in this work gel electrolyte is used as an interlayer
between solid electrolyte and solid electrodes to improve their contact and
reduce their interfacial resistance. The gel electrolyte has a soft structure,
high ionic conductivity, and good wettability. Through construction of the
garnet/gel interlayer/electrode structure, the interfacial resistance of the
garnet significantly decreased from 6.5 * 104 to 248 Omega cm2 for the cathode
and from 1.4 * 103 to 214 Omega cm2 for the Li-metal anode, successfully
demonstrating a full cell with high capacity (140 mAh/g for LiFePO4 cathode) over
70 stable cycles in room temperature. This work provides a binary electrolyte
consisting of gel electrolyte and solid electrolyte to address the interfacial
challenge of solid electrolyte and electrodes and the demonstrated hybrid battery
presents a promising future for battery development with high energy and good
safety.
PMID- 28497950
TI - Deamidation Slows Curli Amyloid-Protein Aggregation.
AB - Nonenzymatic deamidation of asparagine and glutamine in peptides and proteins is
a frequent modification both in vivo and in vitro. The biological effect is not
completely understood, but it is often associated with protein degradation and
loss of biological function. Here we describe the deamidation of CsgA, the major
protein subunit of curli, which are important proteinaceous components of
biofilms. CsgA has a high content of Asn and Gln, a feature seen in a few
proteins that self-aggregate. We have implemented an approach to monitor
deamidation rapidly by following the globally centroid mass shift, providing
guidance for studies at the residue level. From the global mass measurement, we
identified, using LC-MS/MS, extensive deamidation of several Asn residues and
discovered three "Asn-Gly" sites to be the hottest spots for deamidation. The
fibrillization of deamidated CsgA was measured using thioflavin T (ThT)
fluorescence, circular dichroism (CD), and a previously reported hydrogen
deuterium exchange (HDX) platform. Deamidated proteins exhibit a longer lag phase
and lower final ThT fluorescence, strongly suggesting slower and less amyloid
fibril formation. CD spectra show that extensively deamidated CsgA remains
unstructured and loses its ability to form amyloids. Mass-spectrometry-based HDX
also shows that deamidated CsgA aggregates more slowly than wild-type CsgA. Taken
together, the results show that deamidation of CsgA slows its fibrillization and
disrupts its function, suggesting an opportunity to modulate CsgA fibrillization
and affect curli and biofilm formation.
PMID- 28497952
TI - Generalized Subset Designs in Analytical Chemistry.
AB - Design of experiments (DOE) is an established methodology in research,
development, manufacturing, and production for screening, optimization, and
robustness testing. Two-level fractional factorial designs remain the preferred
approach due to high information content while keeping the number of experiments
low. These types of designs, however, have never been extended to a generalized
multilevel reduced design type that would be capable to include both qualitative
and quantitative factors. In this Article we describe a novel generalized
fractional factorial design. In addition, it also provides complementary and
balanced subdesigns analogous to a fold-over in two-level reduced factorial
designs. We demonstrate how this design type can be applied with good results in
three different applications in analytical chemistry including (a) multivariate
calibration using microwave resonance spectroscopy for the determination of water
in tablets, (b) stability study in drug product development, and (c)
representative sample selection in clinical studies. This demonstrates the
potential of generalized fractional factorial designs to be applied in many other
areas of analytical chemistry where representative, balanced, and complementary
subsets are required, especially when a combination of quantitative and
qualitative factors at multiple levels exists.
PMID- 28497953
TI - Fabrication of Highly Stable Metal Oxide Hollow Nanospheres and Their Catalytic
Activity toward 4-Nitrophenol Reduction.
AB - In this paper, hollow nanospheres (HNSs) of metal oxides (NiO, CuO, and NiO/CuO)
coated with a porous carbon shell (HNSs@C) with good structural stability were
successfully prepared on the basis of the nanoscale Kirkendall effect. The
formation process was based on a template-free method, and the as-prepared HNSs@C
are very clean compared with products of the template process. In addition, the
results of N2 adsorption-desorption noted that both the metal oxide HNSs and the
coated carbon were mesoporous structures. Therefore, small molecules can access
the inner space of the whole HNSs@C, which was expected to increase the active
site area and to show better performances in applied fields, such as catalysts
and sensors. As an example of the functional properties, the obtained HNSs@C were
investigated as the catalyst for the hydrogenation of 4-nitrophenol (4-NP) and
manifested highly catalytic activity and excellent stability. This work has
opened up a novel route for the development of metal oxide HNSs nanocatalysts.
This straightforward method is of significance for development of clean metal
oxide HNSs with high stability and multiplied applications.
PMID- 28497954
TI - Metallic Two-Dimensional Nanoframes: Unsupported Hierarchical Nickel-Platinum
Alloy Nanoarchitectures with Enhanced Electrochemical Oxygen Reduction Activity
and Stability.
AB - Electrochemical oxygen reduction reaction (ORR) catalysts that have both high
activities and long-term stabilities are needed for proton-exchange membrane fuel
cells (PEMFCs) and metal-air batteries. Two-dimensional (2D) materials based on
graphene have shown high catalytic activities, however, carbon-based materials
result in significant catalyst degradation due to carbon oxidation that occurs at
high electrochemical potentials. Here, we introduce the synthesis and
electrochemical performance of metallic 2D nanoframes which represent a new
approach to translate 2D materials into unsupported (carbon-free)
electrocatalysts that have both significantly higher ORR catalytic activities and
stabilities compared with conventional Pt/carbon electrocatalysts. Metallic Ni-Pt
2D nanoframes were synthesized by controlled thermal treatments of Pt-decorated
Ni(OH)2 nanosheets. The nanoframes consist of a hierarchical 2D framework
composed of a highly catalytically active Pt-Ni alloy phase with an
interconnected solid and pore network that results in three-dimensional molecular
accessibility. The inclusion of Ni within the Pt structure resulted in
significantly smaller Pt lattice distances compared to those of Pt nanoparticles.
On the basis of its unique local and extended structure, the ORR specific
activity of Ni-Pt 2D nanoframes (5.8 mA cmPt-2) was an order of magnitude higher
than Pt/carbon. In addition, accelerated stability testing at elevated potentials
up to 1.3 VRHE showed that the metallic Ni-Pt nanoframes exhibit significantly
improved stability compared with Pt/carbon catalysts. The nanoarchitecture and
local structure of metallic 2D nanoframes results in high combined specific
activity and elevated potential stability. Analysis of the ORR electrochemical
reaction kinetics on the Ni-Pt nanoframes supports that at low overpotentials the
first electron transfer is the rate-determining step, and the reaction proceeds
via a four electron reduction process. The ability to create metallic 2D
structures with 3D molecular accessibility opens up new opportunities for the
design of high activity and stability carbon-free catalyst nanoarchitectures for
numerous electrocatalytic and catalytic applications.
PMID- 28497955
TI - Synthetic and Therapeutic Applications of Ammonia-lyases and Aminomutases.
AB - Ammonia-lyases and aminomutases are mechanistically and structurally diverse
enzymes which catalyze the deamination and/or isomerization of amino acids in
nature by cleaving or shifting a C-N bond. Of the many protein families in which
these enzyme activities are found, only a subset have been employed in the
synthesis of optically pure fine chemicals or in medical applications. This
review covers the natural diversity of these enzymes, highlighting particular
enzyme classes that are used within industrial and medical biotechnology. These
highlights detail the discovery and mechanistic investigations of these
commercially relevant enzymes, along with comparisons of their various
applications as stand-alone catalysts, components of artificial biosynthetic
pathways and biocatalytic or chemoenzymatic cascades, and therapeutic tools for
the potential treatment of various pathologies.
PMID- 28497956
TI - Engineering of Heterojunction-Mediated Biointerface for Photoelectrochemical
Aptasensing: Case of Direct Z-Scheme CdTe-Bi2S3 Heterojunction with Improved
Visible-Light-Driven Photoelectrical Conversion Efficiency.
AB - This work presents a heterojunction-mediated photoelectrochemical (PEC)
biointerface for selective detection of microcystin-LR (MC-LR) by introducing a
direct Z-scheme heterojunction as efficient visible-light-driven photoactive
species. Specifically, the Z-scheme type CdTe-Bi2S3 heterojunction was designed
and synthesized as an ideal photoactive material, which exhibited higher PEC
activity as compared with either CdTe quantum dots or Bi2S3 nanorods due to the
improved photogenerated charges separation efficiency of heterojunction. Then the
MC-LR aptamer was employed for selective recognition of MC-LR target, which was
immobilized on the CdTe-Bi2S3 film by the formation of phosphor-amidate bonds
between the phosphate group of aptamer and amino group of the chitosan film on
the electrode. The proposed aptasensor showed a photocurrent signal due to the
photoactive CdTe-Bi2S3 heterojunction, while the presence of MC-LR resulted in a
dose-responsive decrease in PEC response, which allowed the quantification
analysis of MC-LR by measuring the photocurrent signal of the fabricated
aptasensor. Under optimal conditions, the resulted PEC aptasensor showed wide
linear range (0.01-100 pM) and low detection limit (0.005 pM) for MC-LR
determination with high selectivity and acceptable reproducibility. Finally, the
proposed aptasensing method was successfully applied in MC-LR detection in real
water samples.
PMID- 28497957
TI - Compression Ratio Ion Mobility Programming (CRIMP) Accumulation and Compression
of Billions of Ions for Ion Mobility-Mass Spectrometry Using Traveling Waves in
Structures for Lossless Ion Manipulations (SLIM).
AB - We report on the implementation of a traveling wave (TW) based compression ratio
ion mobility programming (CRIMP) approach within structures for lossless ion
manipulations (SLIM) that enables both greatly enlarged trapped ion charge
capacities and also efficient ion population compression for use in ion mobility
(IM) separations. Ion accumulation is conducted in a SLIM serpentine ultralong
path with extended routing (SUPER) region after which CRIMP compression allows
the large ion populations to be "squeezed". The SLIM SUPER IM module has two
regions, one operating with conventional traveling waves (i.e., traveling trap;
TT region) and the second having an intermittently pausing or "stuttering" TW
(i.e., stuttering trap; ST region). When a stationary voltage profile was used in
the ST region, ions are blocked at the TT-ST interface and accumulated in the TT
region and then can be released by resuming a conventional TW in the ST region.
The population can also be compressed using CRIMP by the repetitive merging of
ions distributed over multiple TW bins in the TT region into a single TW bin in
the ST region. Ion accumulation followed by CRIMP compression provides the basis
for the use of larger ion populations for IM separations. We show that over 109
ions can be accumulated with high efficiency in the present device and that the
extent of subsequent compression is only limited by the space charge capacity of
the trapping region. Approximately 5 * 109 charges introduced from an
electrospray ionization source were trapped for a 40 s accumulation period, more
than 2 orders of magnitude greater than the previously reported charge capacity
of an ion funnel trap. Importantly, we show that extended ion accumulation in
conjunction with CRIMP compression and multiple passes through the serpentine
path provides the basis for a highly desirable combination of ultrahigh
sensitivity and SLIM SUPER high-resolution IM separations.
PMID- 28497958
TI - Structural Motifs of [Fe(CO2)n]- Clusters (n = 3-7).
AB - We present IR spectra and quantum chemical calculations for anionic iron-CO2
clusters of the form [Fe(CO2)n]- (n = 3-7). All observed clusters have at least
two CO2 units strongly bound to the metal atom. These strongly bound iron-CO2
complexes form the core ions of the clusters and are solvated by additional,
weakly bound CO2 molecules. Larger clusters show clear infrared signatures of
core ion isomers with three CO2 moieties as well. Dominant structural motifs are
based on bidentate CO2 ligands with Fe-O/Fe-C bonds, oxalate ligands, and metal
insertion into a CO bond.
PMID- 28497959
TI - Characterization of Agronomy, Grain Physicochemical Quality, and Nutritional
Property of High-Lysine 35R Transgenic Rice with Simultaneous Modification of
Lysine Biosynthesis and Catabolism.
AB - Lysine is the first limiting essential amino acid in rice. We previously
constructed a series of transgenic rice lines to enhance lysine biosynthesis
(35S), down-regulate its catabolism (Ri), or simultaneously achieve both
metabolic effects (35R). In this study, nine transgenic lines, three from each
group, were selected for both field and animal feeding trials. The results showed
that the transgene(s) caused no obvious effects on field performance and main
agronomic traits. Mature seeds of transgenic line 35R-17 contained 48-60-fold
more free lysine than in wild type and had slightly lower apparent amylose
content and softer gel consistency. Moreover, a 35-day feeding experiment showed
that the body weight gain, food efficiency, and protein efficiency ratio of rats
fed the 35R-17 transgenic rice diet were improved when compared with those fed
wild-type rice diet. These data will be useful for further evaluation and
potential commercialization of 35R high-lysine transgenic rice.
PMID- 28497961
TI - Evaluating the Development of Biocatalytic Technology for the Targeted Removal of
Perchlorate from Drinking Water.
AB - Removing micropollutants is challenging in part because of their toxicity at low
concentrations. A biocatalytic approach could harness the high affinity of
enzymes for their substrates to address this challenge. The potential of
biocatalysis relative to mature (nonselective ion exchange, selective ion
exchange, and whole-cell biological reduction) and emerging (catalysis)
perchlorate-removal technologies was evaluated through a quantitative sustainable
design framework, and research objectives were prioritized to advance economic
and environmental sustainability. In its current undeveloped state, the
biocatalytic technology was approximately 1 order of magnitude higher in cost and
environmental impact than nonselective ion exchange. Biocatalyst production was
highly correlated with cost and impact. Realistic improvement scenarios targeting
biocatalyst yield, biocatalyst immobilization for reuse, and elimination of an
electron shuttle could reduce total costs to $0.034 m-3 and global warming
potential (GWP) to 0.051 kg CO2 eq m-3: roughly 6.5% of cost and 7.3% of GWP of
the background from drinking water treatment and competitive with the best
performing technology, selective ion exchange. With less stringent perchlorate
regulatory limits, ion exchange technologies had increased cost and impact, in
contrast to biocatalytic and catalytic technologies. Targeted advances in
biocatalysis could provide affordable and sustainable treatment options to
protect the public from micropollutants.
PMID- 28497960
TI - Using Dynamic Covalent Chemistry To Drive Morphological Transitions: Controlled
Release of Encapsulated Nanoparticles from Block Copolymer Vesicles.
AB - Dynamic covalent chemistry is exploited to drive morphological order-order
transitions to achieve the controlled release of a model payload (e.g., silica
nanoparticles) encapsulated within block copolymer vesicles. More specifically,
poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate) (PGMA-PHPMA)
diblock copolymer vesicles were prepared via aqueous polymerization-induced self
assembly in either the presence or absence of silica nanoparticles. Addition of 3
aminophenylboronic acid (APBA) to such vesicles results in specific binding of
this reagent to some of the pendent cis-diol groups on the hydrophilic PGMA
chains to form phenylboronate ester bonds in mildly alkaline aqueous solution (pH
~ 10). This leads to a subtle increase in the effective volume fraction of this
stabilizer block, which in turn causes a reduction in the packing parameter and
hence induces a vesicle-to-worm (or vesicle-to-sphere) morphological transition.
The evolution in copolymer morphology (and the associated sol-gel transitions)
was monitored using dynamic light scattering, transmission electron microscopy,
oscillatory rheology, and small-angle X-ray scattering. In contrast to the
literature, in situ release of encapsulated silica nanoparticles is achieved via
vesicle dissociation at room temperature; moreover, the rate of release can be
fine-tuned by varying the solution pH and/or the APBA concentration. Furthermore,
this strategy also works (i) for relatively thick-walled vesicles that do not
normally exhibit stimulus-responsive behavior and (ii) in the presence of added
salt. This novel molecular recognition strategy to trigger morphological
transitions via dynamic covalent chemistry offers considerable scope for the
design of new stimulus-responsive copolymer vesicles (and hydrogels) for targeted
delivery and controlled release of cargoes. In particular, the conditions used in
this new approach are relevant to liquid laundry formulations, whereby enzymes
require protection to prevent their deactivation by bleach.
PMID- 28497962
TI - Potential of Polygonum cuspidatum Root as an Antidiabetic Food: Dual High
Resolution alpha-Glucosidase and PTP1B Inhibition Profiling Combined with HPLC
HRMS and NMR for Identification of Antidiabetic Constituents.
AB - The worldwide increasing incidence of type 2 diabetes has fueled an intensified
search for food and herbal remedies with preventive and/or therapeutic
properties. Polygonum cuspidatum Siebold & Zucc. (Polygonaceae) is used as a
functional food in Japan and South Korea, and it is also a well-known traditional
antidiabetic herb used in China. In this study, dual high-resolution alpha
glucosidase and protein-tyrosine phosphatase 1B (PTP1B) inhibition profiling was
used for the identification of individual antidiabetic constituents directly from
the crude ethyl acetate extract and fractions of P. cuspidatum. Subsequent
preparative-scale HPLC was used to isolate a series of alpha-glucosidase
inhibitors, which after HPLC-HRMS and NMR analysis were identified as procyanidin
B2 3,3"-O-digallate (3) and (-)-epicatechin gallate (5) with IC50 values of 0.42
+/- 0.02 and 0.48 +/- 0.0004 MUM, respectively, as well as a series of stilbene
analogues with IC50 value in the range from 6.05 +/- 0.05 to 116.10 +/- 2.04 MUM.
In addition, (trans)-emodin-physcion bianthrone (15b) and (cis)-emodin-physcion
bianthrone (15c) were identified as potent PTP1B inhibitors with IC50 values of
2.77 +/- 1.23 and 7.29 +/- 2.32 MUM, respectively. These findings show that P.
cuspidatum is a potential functional food for management of type 2 diabetes.
PMID- 28497963
TI - IR Spectra of n-Bu4M (M = Si, Ge, Sn, Pb), n-BuAuPPh3-d15, and "n-Bu" on a Gold
Surface.
AB - Observed and DFT-calculated IR spectra of n-Bu4M (M = Si, Ge, Sn, Pb),
(CH3CH2CH213CD2)4Sn, and n-BuAuPPh3-d15 are reported and assigned. The asymmetric
CH stretching vibration of the CH2 group adjacent to the metal atom appears as a
distinct shoulder at ~2934 cm-1, whereas for other CH2 groups it is located at
~2922 cm-1. The characteristic peak at ~2899 cm-1 is attributed to an overtone of
a symmetric CH2 bend at ~1445 cm-1. In n-BuAuPPh3-d15, the CH stretching
vibrations of the butyl group are shifted to lower frequencies by ~10 cm-1, and
two possible rationalizations are offered.
PMID- 28497964
TI - Biosynthetic Origin of the Hydroxamic Acid Moiety of Trichostatin A:
Identification of Unprecedented Enzymatic Machinery Involved in Hydroxylamine
Transfer.
AB - Trichostatin A (TSA) is widely used in the field of epigenetics because it
potently inhibits histone deacetylase (HDAC). In-depth studies have revealed that
the hydroxamic acid group in TSA chelates the zinc(II) ion in the active site of
HDAC to realize the inhibitory activity. Here we report the first identification
of a complete TSA biosynthetic gene cluster from Streptomyces sp. RM72 and the
heterologous production of TSA in Streptomyces albus. Biochemical analyses
unambiguously demonstrate that unprecedented biosynthetic machinery catalyzes the
direct transfer of hydroxylamine from a nonproteinogenic amino acid, l-glutamic
acid gamma-monohydroxamate, to the carboxylic acid group of trichostatic acid to
form the hydroxamic acid moiety of TSA. The present study establishes the
biosynthetic pathway of TSA, paving the way toward understanding the biosynthesis
of other hydroxamic acid-containing natural products.
PMID- 28497965
TI - Residues of Alpha Helix H3 Determine Distinctive Features of Transforming Growth
Factor beta3.
AB - Transforming growth factors (TGF-betas) are proteins that regulate cell growth by
binding to their receptors. In contrast to transforming growth factor (TGF)
beta1, TGF-beta3 homodimer is believed to exist also in an open conformation, in
which both of its monomers are loosely packed against each other. At the origin
of this difference is the H3-helix. Its sequence and degree of structuration seem
to govern the outcome of TGF dimerization. We docked two monomers of TGF-beta3
with intact and altered H3 alpha-helix against each other using HADDOCK. TGF
beta3 monomer with an intact H3-helix exclusively forms closed conformations of
homodimer, whereas the open conformation may coexist with the closed one when a
part of the H3 alpha-helix is destabilized. We quantify the difference in its
conformational preference for the open versus the closed structure by calculating
the binding energy between monomers using the MMPBSA approach. We compare the
wild type (wt) TGFbeta3/TGFbeta1 homodimers in the Protein Data Bank to a swapped
mutant where all residues of the H3-helix were mutated to the respective
TGFbeta1/TGFbeta3 sequence. Swapping stabilizes the closed conformation and
destabilizes the open conformation of TGFbeta3. Further detailed insight is
derived from molecular dynamics simulation studies suggesting that Val 61 of the
H3-helix may act as an anchor residue for the closed conformation of TGFbeta3.
Computational alanine scanning mutagenesis confirms that several residues of the
H3-helix are the hot residues for the closed conformation of TGFbeta3. These
observations may bear relevance to general conformational transitions in proteins
and specifically in the TGFbeta superfamily.
PMID- 28497966
TI - Large-Scale Analysis of Hydrogen Bond Interaction Patterns in Protein-Ligand
Interfaces.
AB - Protein-ligand interactions are the fundamental basis for molecular design in
pharmaceutical research, biocatalysis, and agrochemical development. Especially
hydrogen bonds are known to have special geometric requirements and therefore
deserve a detailed analysis. In modeling approaches a more general description of
hydrogen bond geometries, using distance and directionality, is applied. A first
study of their geometries was performed based on 15 protein structures in 1982.
Currently there are about 95 000 protein-ligand structures available in the PDB,
providing a solid foundation for a new large-scale statistical analysis. Here, we
report a comprehensive investigation of geometric and functional properties of
hydrogen bonds. Out of 22 defined functional groups, eight are fully in
accordance with theoretical predictions while 14 show variations from expected
values. On the basis of these results, we derived interaction geometries to
improve current computational models. It is expected that these observations will
be useful in designing new chemical structures for biological applications.
PMID- 28497967
TI - Interactions of Metal-Based and Ligand-Based Electronic Spins in Neutral
Tripyrrindione pi Dimers.
AB - The ability of tetrapyrrolic macrocycles to stabilize unpaired electrons and
engage in pi-pi interactions is essential for many electron-transfer processes in
biology and materials engineering. Herein, we demonstrate that the formation of
pi dimers is recapitulated in complexes of a linear tripyrrolic analogue of
naturally occurring pigments derived from heme decomposition.
Hexaethyltripyrrindione (H3TD1) coordinates divalent transition metals (i.e., Pd,
Cu, Ni) as a stable dianionic radical and was recently described as a robust
redox-active ligand. The resulting planar complexes, which feature a delocalized
ligand-based electronic spin, are stable at room temperature in air and support
ligand-based one-electron processes. We detail the dimerization of neutral
tripyrrindione complexes in solution through electron paramagnetic resonance
(EPR) and visible absorption spectroscopic methods. Variable-temperature
measurements using both EPR and absorption techniques allowed determination of
the thermodynamic parameters of pi dimerization, which resemble those previously
reported for porphyrin radical cations. The inferred electronic structure,
featuring coupling of ligand-based electronic spins in the pi dimers, is
supported by density functional theory (DFT) calculations.
PMID- 28497968
TI - Chemoenzymatic Synthesis and alpha-Glucosidase Inhibitory Activity of Dimeric
Neolignans Inspired by Magnolol.
AB - A chemoenzymatic synthesis of a small library of dimeric neolignans inspired by
magnolol (1) is reported. The 2-iodoxybenzoic acid (IBX)-mediated regioselective
ortho-hydroxylation of magnolol is described, affording the bisphenols 6 and 7.
Further magnolol analogues (12, 13, 15-17, 19-23) were obtained from eugenol (3),
tyrosol (4), and homovanillic alcohol (5), through horseradish peroxidase (HRP)
mediated oxidative coupling and regioselective ortho-hydroxylation or ortho
demethylation in the presence of IBX, followed by reductive treatment with
Na2S2O4. A chemoselective protection/deprotection of the alcoholic group of 4 and
5 was carried out by lipase-mediated acetylation/deacetylation. The dimeric
neolignans, together with 1 and honokiol (2), were evaluated as inhibitors of
yeast alpha-glucosidase, in view of their possible utilization and optimization
as antidiabetic drugs. The synthetic analogues of magnolol showed a strong
inhibitory activity with IC50 values in the range 0.15-4.1 MUM, much lower than
those of honokiol and the reference compounds quercetin and acarbose. In
particular, a very potent inhibitory activity, with an IC50 of 0.15 MUM, was
observed for 1,1'-dityrosol-8,8'-diacetate (15), and comparable inhibitory
activities were also shown by bisphenols 6 (0.49 MUM), 13 (0.50 MUM), and 22
(0.86 MUM). A kinetic study showed that 15 acts as a competitive inhibitor, with
a Ki value of 0.86 MUM.
PMID- 28497969
TI - Synthesis of Benzoquinolizinium Salts by Rh(III)-Catalyzed Cascade Double N
Annulation Reactions of Allylamines, Diarylacetylenes, and HBF4.
AB - A new cascade double N-annulation method has been developed for the synthesis of
benzoquinolizinium salts. The process takes place between allylamines, internal
alkynes, and HBF4 in the presence of Rh(III)/Cu(II) complexes and leads to
formation of multisubstituted benzoquinolizinium salts. Importantly, the
resulting benzoquinolizinium salts serve as fluorescent materials whose emission
wavelengths can be tuned by selection of appropriate substituents.
PMID- 28497970
TI - Electrowetting of Weak Polyelectrolyte-Coated Surfaces.
AB - Polymer coatings are commonly used to modify interfacial properties like
wettability, lubrication, or biocompatibility. These properties are determined by
the conformation of polymer molecules at the interface. Polyelectrolytes are
convenient elementary bricks to build smart materials, given that polyion chain
conformation is very sensitive to different environmental variables. Here we
discuss the effect of an applied electric field on the properties of surfaces
coated with poly(acrylic acid) brushes. By combining atomic force microscopy,
quartz crystal microbalance, and contact angle experiments, we show that it is
possible to precisely tune polyion chain conformation, surface adhesion, and
surface wettability using very low applied voltages if the polymer grafting
density and environmental conditions (pH and ionic strength) are properly
formulated. Our results indicate that the effective ionization degree of the
grafted weak polyacid can be finely controlled with the externally applied field,
with important consequences for the macroscopic surface properties.
PMID- 28497971
TI - 9,9-Difluorobispidine Analogues of Cisplatin, Carboplatin, and Oxaliplatin.
AB - As part of a comprehensive study of N-unsubstituted bispidines, the novel 9,9
difluorobispidine (D) has been synthesized. The compound crystallizes from
pentane below 0 degrees C in the ordered-crystalline phase D-II and undergoes at
0-30 degrees C a stepwise endothermic phase transition to a dynamically
disordered crystalline phase D-I; melting occurs at 227 degrees C. Single
crystalline D-II has been subjected to X-ray structure analysis, revealing
association of the molecules to form chains. Reaction of (1,5-hexadiene)PtCl2
with D affords {C7H10F2(NH)2}PtCl2 (D1), which can be converted by conventional
routes to {C7H10F2(NH)2}Pt(cbdca).5H2O (D2) and {C7H10F2(NH)2}Pt(C2O4) (D3).
Compound D1 crystallizes solvent-free from water and is isomorphous to the
solvent-free parent bispidine analogue (A1). The pentahydrate D2 is isomorphous
to the bispidine and 9-oxabispidine homologues (A2 and C2), as shown by X-ray
structure analyses. An increased polarity of the bispidine skeleton as a
consequence of the high electronegativity of fluorine is seen as the reason for
low cytotoxic potency of D1-D3.
PMID- 28497972
TI - Organocatalytic Asymmetric Annulation between Hydroxymaleimides and
Nitrosoarenes: Stereoselective Preparation of Chiral Quaternary N
Hydroxyindolines.
AB - An unusual and highly effective asymmetric annulation of nitrosoarenes with
hydroxymaleimides catalyzed by a chiral bifunctional amine squaramide catalyst
has been disclosed. A wide range of highly fused chiral N-hydroxyindolines with
two consecutive quaternary stereocenters and multifunctional groups were directly
and effectively prepared in excellent yields (up to >99%) with complete
regioselective cyclization and excellent stereoselectivities (up to >99:1 dr and
>99% ee). The efficiency and potentials of the new reaction and the target chiral
entities were well demonstrated by delicate transformations into a series of new
chiral indolines.
PMID- 28497973
TI - Construction of Chiral-Fused Tricyclic gamma-Lactams via a trans-Perhydroindolic
Acid-Catalyzed Asymmetric Domino Reaction.
AB - An asymmetric domino reaction was developed utilizing readily available cyclic
alpha-dehydroamino ketones and aldehydes, which when subjected a 2-iodoxybenzoic
acid (IBX)-mediated oxidation gives pyrrolidinone-containing tricyclic
derivatives. trans-Perhydroindolic acid proved to be an efficient organocatalyst
in this reaction (up to 94% yield, 99% ee, and >20:1 dr). The product could be
conveniently converted to synthetically useful intermediates via simple
transformations. A possible stereocontrolled process has been suggested according
to X-ray crystallography studies.
PMID- 28497974
TI - Carbon Nanotube and Semiconductor Nanorods Hybrids: Preparation,
Characterization, and Evaluation of Photocurrent Generation.
AB - Carbon nanotubes (CNTs) and semiconductor nanocrystals (SCNCs) are known to be
interesting donor-acceptor partners due to their unique optical and electronic
properties. These exciting features have led to the development of novel
composites based on these two nanomaterials and to their characterization for use
in various applications, such as components in sensors, transistors, solar cells
and biomedical devices. Two approaches based on covalent and noncovalent methods
have been suggested for coupling the SCNCs to CNTs. Most covalent conjugation
methods used so far were found to disrupt the electronic structure of the CNTs or
interfere with charge transfer in the CNT-SCNC interface. Moreover, it offers
random and poorly organized nanoparticle coatings. Therefore, noncovalent methods
are considered to be ideal for better electronic coupling. However, a key common
drawback of noncovalent methods is the lack of stability which hampers their
applicability. In this article, a method has been developed to couple
semiconductor seeded nanorods onto CNTs through pi-pi interactions. The CNTs and
pyrene conjugated SCNC hybrid materials were characterized by both microscopic
and spectroscopic techniques. Fluorescence and photocurrent measurements suggest
the proposed pi-stacking approach results in a strong electronic coupling between
the CNTs and the SCNCs leading to better photocurrent efficiency than that of a
covalent conjugation method reported using similar SCNC material. Overall, the
CNT-SCNC films reported in the present study open the scope for the fabrication
of optoelectronic devices for various applications.
PMID- 28497976
TI - Copper(I)-Catalyzed Interrupted Click Reaction with TMSCF3: Synthesis of 5
Trifluoromethyl 1,2,3-Triazoles.
AB - We herein describe a Cu(I)-catalyzed interrupted click reaction, using
(trifluoromethyl)trimethylsilane (TMSCF3) as a nucleophilic CF3 source, to
synthesize 5-trifluoromethyl 1,2,3-triazoles in one step from readily available
terminal alkynes and azides. The reaction shows complete regioselectivity, broad
substrate scope, and good functional group tolerability. The application of the
reaction has been demonstrated in the synthesis of a trifluoromethylated analog
of antiepileptic drug rufinamide.
PMID- 28497975
TI - Adjuvants Based on Synthetic Mycobacterial Cord Factor Analogues: Biophysical
Properties of Neat Glycolipids and Nanoself-Assemblies with DDA.
AB - Synthetic mycobacterial cord factor analogues, e.g., trehalose 6,6'-dibehenate
(TDB), are highly promising adjuvants due to their strong immunopotentiating
capabilities, but their biophysical properties have remained poorly
characterized. Here, we report the synthesis of an array of synthetic TDB
analogues varying in acyl chain length, degree of acylation, and headgroup
display, which was subjected to biophysical characterization of neat nondispersed
self-assembled nanostructures in excess buffer and as aqueous dispersions with
cationic dimethyldioctadecylammonium (DDA) bromide. The array comprised trehalose
mono- (TMX) and diester (TDX) analogues with symmetrically shortened acyl chains
[denoted by X: arachidate (A), stearate (S), palmitate (P), myristate (Myr), and
laurate (L)] and an analogue with a short hydrophilic polyethylene glycol (PEG)
linker inserted between the trehalose headgroup of TDS and the acyl chains (PEG
TDS). All dispersions were liposomes, but in contrast to the colloidally stable
and highly cationic TDX-containing liposomes, the zeta-potential was
significantly reduced for DDA/TMX and DDA/PEG-TDS liposomes, suggesting a charge
shielding effect, which compromises the colloidal stability. An increased d
spacing was observed for the lamellar phase of neat TDB analogues in excess
buffer (TDS < TMS < PEG-TDS), confirming that the charge shielding is caused by
an extended molecular configuration of the more flexible headgroup. Differential
scanning calorimetry showed highly cooperative phase transitions for all tested
dispersions albeit the monoesters destabilized the lipid bilayers. Langmuir
experiments demonstrated that incorporation of TDXs and PEG-TDS stabilized DDA
monolayers due to improved hydrogen bonding and reduced intermolecular
repulsions. In conclusion, data suggest that the DDA/TDS dispersions exhibit
favorable physicochemical properties rendering these DDA/TDS liposomes an
attractive vaccine adjuvant, and they emphasize that not only the receptor
binding and immune activation but also the biophysical properties of
immunopotentiator formulations should be collectively considered when designing
adjuvants with optimal safety, efficacy, and storage stability.
PMID- 28497977
TI - Effect of Amino Acid Substitutions Within the V3 Region of HIV-1 CRF01_AE on
Interaction with CCR5-Coreceptor.
AB - Specific amino acids within the V3 loop of HIV-1 CRF01_AE envelope glycoprotein
that are involved in the interaction with CCR5/CXCR4 coreceptors, are not well
characterized. We generated V3 mutants using polymerase chain reaction (PCR)
based site-directed mutagenesis of HIV-1 CRF01_AE R5-env plasmids at specific
positions. Mutant viruses were produced by env-pseudotyped virus assay, tested
for coreceptor usage using U373.R5 and U373.X4 cells, and viral entry was
assessed with luciferase activity measurement. All viruses, harboring either
single or double mutations, used the CCR5 coreceptor. However, those containing a
single substitution at positions 7, 11, 18, and 32 and those with mutations at
positions 5/32 and 18/32 had reduced infectivity. Only virus with arginine
substitution at position 11 seemed to be involved in CXCR4 coreceptor usage. Our
results suggest that some V3 positions may be necessary for the binding to
coreceptor, but not for the switch of coreceptor usage.
PMID- 28497978
TI - Extraction and Quantitation of Nicotinamide Adenine Dinucleotide Redox Cofactors.
AB - AIMS: Accurate analysis of dinucleotide redox cofactors nicotinamide adenine
dinucleotide phosphate reduced (NADPH), nicotinamide adenine dinucleotide
phosphate (NADP+), nicotinamide adenine dinucleotide reduced (NADH), and
nicotinamide adenine dinucleotide (NAD+) from biological samples is important to
understanding cellular redox homeostasis. In this study, we aimed to develop a
simple protocol for quenching metabolism and extracting NADPH that avoids
interconversion among the reduced forms and the oxidized forms. RESULTS: We
compared seven different solvents for quenching and extraction of cultured
mammalian cells and mouse tissues: a cold aqueous buffer commonly used in enzyme
assays with and without detergent, hot aqueous buffer, and cold organic mixtures
(80% methanol, buffered 75% acetonitrile, and acidic 40:40:20
acetonitrile:methanol:water with either 0.02 M or 0.1 M formic acid). Extracts
were analyzed by liquid chromatography-mass spectrometry (LC-MS). To monitor the
metabolite interconversion, cells were grown in 13C6-glucose medium, and
unlabeled standards were spiked into the extraction solvents. Interconversion
between the oxidized and reduced forms was substantial except for the enzyme
assay buffer with detergent, 80% methanol and 40:40:20
acetonitrile:methanol:water, with the 0.1 M formic acid mix giving the least
interconversion and best recoveries. Absolute NAD+, NADH, NADP+, and NADPH
concentrations in cells and mouse tissues were measured with this approach.
INNOVATION: We found that the interconversion between the reduced and oxidized
forms during extraction is a major barrier to accurately measuring NADPH/NADP+
and NADH/NAD+ ratios. Such interconversion can be monitored by isotope labeling
cells and spiking NAD(P)(H) standards. CONCLUSION: Extraction with 40:40:20
acetonitrile:methanol:water with 0.1 M formic acid decreases interconversion and,
therefore, is suitable for measurement of redox cofactor ratios using LC-MS. This
solvent is also useful for general metabolomics. Samples should be neutralized
immediately after extraction to avoid acid-catalyzed degradation. When LC-MS is
not available and enzyme assays are accordingly used, inclusion of detergent in
the aqueous extraction buffer reduces interconversion. Antioxid. Redox Signal.
28, 167-179.
PMID- 28497979
TI - Sensitive Detection of Rhodamine B in Condiments Using Surface-Enhanced Resonance
Raman Scattering (SERRS) Silver Nanowires as Substrate.
AB - In this paper, a facile large-scale preparation of surface-enhanced resonance
Raman scattering (SERRS) substrates for the determination of Rhodamine B (RhB)
based on silver nanowires (Ag NWs) has been developed. The morphology, structure,
and properties of as-prepared Ag NWs are characterized using ultraviolet-visible
(UV-Vis) spectroscopy, field emission scanning electron microscopy (FE-SEM), and
X-ray diffraction (XRD), respectively. Ag NWs were assembled onto glass slides
through a self-assembly method. Moreover, in our experiment, as-prepared Ag
NWs@glass were used as a SERRS substrate to detect RhB at the excitation
wavelength of 532 nm. Experimental conditions such as pH value and soaking time
on SERRS performance were studied and optimized. Under the optimized conditions,
the SERRS intensity at 1648 cm-1 exhibited a linear relationship with the
concentration of RhB in the range of 1.0 * 10-9-1.0 * 10-5 mol L-1 and detection
limit (signal-to-noise ratio [S/N] = 3) is as low as 0.3 nmol L-1. The
corresponding correlation coefficient of the linear equation was 0.996. This
method based on Ag NWs@glass for the detection of RhB in three kinds of condiment
was investigated. The limits of detection (LODs) for RhB were 0.35 ug/g in chili
powder, 0.14 ug/g in chili sauce, and 0.02 ug/g in Chinese prickly ash. The
relative standard deviations (RSD) were between 2.18% and 4.56% (n = 3) and
recoveries at three levels were in the range of 80.0-98.7% for different spiked
food products. Moreover, the results showed that the proposed method was
sensitive, convenient, and feasible for the determination of RhB in condiments.
PMID- 28497980
TI - The association between cigarette smoking, virologic suppression, and CD4+
lymphocyte count in HIV-Infected Russian women.
AB - Cigarette smoking among people living with HIV/AIDS is associated with
significant morbidity and mortality, but findings regarding the association
between cigarette smoking and HIV viral load and CD4+ lymphocyte counts have been
inconsistent. This study characterized the prevalence of cigarette smoking among
HIV-infected Russian women and examined the association between smoking frequency
and quantity and HIV viral load and CD4+ lymphocyte counts. HIV-infected Russian
women (N = 250; M age = 30.0) in St. Petersburg, Russia, completed an audio
computer-assisted self-interview survey assessing cigarette use, antiretroviral
medication adherence, and provided blood samples assayed for HIV viral load and
CD4+ lymphocyte counts. The majority (60.4%) reported cigarette smoking in the
past month; 49.0% of recent smokers were classified as moderate or heavy smokers,
defined as smoking >=10 cigarettes daily. Viral load status did not differ
between infrequent smokers and regular smokers. However, moderate/heavy smokers
(relative to light smokers) were more likely to have a detectable viral load (AOR
= 2.3, 95% CI: 1.1, 5.1). There were no significant differences in CD4+
lymphocyte counts by smoking frequency or quantity of cigarettes smoked. Results
highlight the need for additional research to examine the association between
cigarette smoking and virologic suppression and markers of HIV disease
progression. Adverse health consequences of cigarette smoking coupled with a
potential link between heavy smoking and poor virologic suppression highlight the
need for assessment of cigarette use and provision of evidence-based smoking
cessation interventions within HIV medical care.
PMID- 28497981
TI - Measurement of Cerium and Gadolinium in Solid Lithium Chloride-Potassium Chloride
Salt Using Laser-Induced Breakdown Spectroscopy (LIBS).
AB - Pyroprocessing of used nuclear fuel (UNF) has many advantages-including that it
is proliferation resistant. However, as part of the process, special nuclear
materials accumulate in the electrolyte salt and present material accountability
and safeguards concerns. The main motivation of this work was to explore a laser
induced breakdown spectroscopy (LIBS) approach as an online monitoring technique
to enhance the material accountability of special nuclear materials in
pyroprocessing. In this work, a vacuum extraction method was used to draw the
molten salt (CeCl3-GdCl3-LiCl-KCl) up into 4 mm diameter Pyrex tubes where it
froze. The salt was then removed and the solid salt was measured using LIBS and
inductively coupled plasma mass spectroscopy (ICP-MS). A total of 36 samples were
made that varied the CeCl3 and GdCl3 (surrogates for uranium and plutonium,
respectively) concentrations from 0.5 wt% to 5 wt%. From these samples,
univariate calibration curves for Ce and Gd were generated using peak area and
peak intensity methods. For Ce, the Ce 551.1 nm line using the peak area provided
the best calibration curve with a limit of detection (LOD) of 0.099 wt% and a
root mean squared error of cross-validation (RMSECV) of 0.197 wt%. For Gd, the
best curve was generated using the peak intensities of the Gd 564.2 nm line
resulting in a LOD of 0.027 wt% and a RMSECV of 0.295 wt%. The RMSECV for the
univariate cases were determined using leave-one-out cross-validation. In
addition to the univariate calibration curves, partial least squares (PLS)
regression was done to develop a calibration model. The PLS models yielded
similar results with RMSECV (determined using Venetian blind cross-validation
with 17% left out per split) values of 0.30 wt% and 0.29 wt% for Ce and Gd,
respectively. This work has shown that solid pyroprocessing salt can be
qualitatively and quantitatively monitored using LIBS. This work has the
potential of significantly enhancing the material monitoring and safeguards of
special nuclear materials in pyroprocessing.
PMID- 28497983
TI - Promoting Responsible Electronic Documentation: Validity Evidence for a Checklist
to Assess Progress Notes in the Electronic Health Record.
AB - : Construct: We aimed to develop an instrument to measure the quality of
inpatient electronic health record- (EHR-) generated progress notes without
requiring raters to review the detailed chart or know the patient. BACKGROUND:
Notes written in EHRs have generated criticism for being unnecessarily long and
redundant, perpetuating inaccuracy and obscuring providers' clinical reasoning.
Available assessment tools either focus on outpatient progress notes or require
chart review by raters to develop familiarity with the patient. APPROACH: We used
medical literature, local expert review, and attending focus groups to develop
and refine an instrument to evaluate inpatient progress notes. We measured
interrater reliability and scored the selected-response elements of the checklist
for a sample of 100 progress notes written by PGY-1 trainees on the general
medicine service. RESULTS: We developed an instrument with 18 selected-response
items and four open-ended items to measure the quality of inpatient progress
notes written in the EHR. The mean Cohen's kappa coefficient demonstrated good
agreement at .67. The mean note score was 66.9% of maximum possible points (SD =
10.6, range = 34.4%-93.3%). CONCLUSIONS: We present validity evidence in the
domains of content, internal structure, and response process for a new checklist
for rating inpatient progress notes. The scored checklist can be completed in
approximately 7 minutes by a rater who is not familiar with the patient and can
be done without extensive chart review. We further demonstrate that trainee notes
show substantial room for improvement.
PMID- 28497985
TI - Examining Medical Student Specialty Choice Through a Gender Lens: An
Orientational Qualitative Study.
AB - : Phenomenon: A growing number of women are entering the medical workforce, yet
their distribution across medical specialties remains nonuniform. We sought to
describe how culture, bias, and socialization shape gendered thinking regarding
specialty choice at a Canadian undergraduate medical institution. APPROACH: We
analyzed transcripts from the Career Choices Project: 16 semistructured focus
group discussions with 70 students graduating from Memorial University of
Newfoundland in 2003, 2006, 2007, and 2008. The questions and prompts were
designed to explore factors influencing specialty choice and did not specifically
probe gender-based experiences. Focus groups were audio-recorded, transcribed,
and deidentified before analysis. Analysis was inductive and guided by principles
of orientational qualitative inquiry using a gender-specific lens. FINDINGS: The
pursuits of personal and professional goals, as well as contextual factors, were
the major themes that influenced decision-making for women and men. Composition
of these major themes varied between genders. Influence of a partner,
consideration of familial commitments (both present and future), feeling a sense
of connectedness with the field in question, and social accountability were
described by women as important. Both genders hoped to pursue careers that would
afford "flexibility" in order to balance work with their personal lives, though
the construct of work-life balance differed between genders. Women did not
explicitly identify gender bias or sexism as influencing factors, but their
narratives suggest that these elements were at play. Insights: Our findings
suggest that unlike men, women's decision-making is informed by tension between
personal and professional goals, likely related to the context of gendered
personal and societal expectations.
PMID- 28497984
TI - Recovery of Working Memory Following Pediatric Traumatic Brain Injury: A
Longitudinal Analysis.
AB - In a prospective longitudinal study, the trajectory of verbal and visual-spatial
working memory (WM) development was examined 2-, 6-, 12-, and 24-months following
complicated-mild to severe pediatric traumatic brain injury (TBI; n = 55)
relative to an orthopedic injury comparison group (n = 47). Individual growth
curve modeling revealed an interaction of age, severity, and time for verbal, but
not visual-spatial WM. The youngest children with severe TBI had the lowest
scores and slowest verbal WM growth. WM outcome is best understood in light of
age at injury and TBI severity. Findings support the early vulnerability
hypothesis and highlight the need for long-term follow-up.
PMID- 28497986
TI - Traditional Chinese Medicine on the Treatment of Coronary Heart Disease in Recent
20 Years.
AB - OBJECTIVE: To analyze the patterns and differences of Chinese herbs in the
treatment of coronary heart disease (CHD) in different time periods and different
regions in recent 20 years. DESIGN: The literature of controlled clinical trials
that focuses on Chinese herbs treating CHD published in China National Knowledge
Internet and Wanfang database from January 1, 1996 to December 31, 2015 were
screened to analyze the patterns of herb utilization using SPSS 21.0. RESULTS: A
total of 1250 articles were enrolled in total covering 29 regions. There were 242
kinds of single herbs, 18 categories, mentioned a total of 11,594 times. In
Northeast China, North China, South China, Central China, and Southwest China the
most frequently used herb was Radix Salviae Miltiorrhizae, but in East China and
Northwest China, the most frequently used herb was Rhizoma Chuanxiong. The most
frequently used herb category in North China, Central China, Southwest China, and
Northwest China was herbs to invigorate blood, but in Northeast China, East
China, and South China the most frequently used herb category was herbs to
tonify. CONCLUSION: Single herbs and herb categories to treat CHD in Traditional
Chinese Medicine differed from time to time and from region to region.
PMID- 28497987
TI - Elevated Activating Transcription Factor 4 and Glucose-Regulated 78 Kda Protein
Levels Correlate with Inflammatory Cytokines in the Aqueous Humor and Vitreous of
Proliferative Diabetic Retinopathy.
AB - PURPOSE: To determine concentrations of endoplasmic reticulum (ER) stress-related
factors activating transcription factor 4 (ATF4) and glucose-regulated 78 kDa
protein (GRP78) in vitreous and aqueous humor (AqH) of patients with
proliferative diabetic retinopathy (PDR) and the correlation of ATF4, GRP78 and
inflammatory cytokines interleukin-6(IL-6) and monocyte chemoattractant protein-1
(MCP-1). MATERIALS AND METHODS: AqH and vitreous samples were collected from eyes
of patients with PDR and idiopathic macular hole (IMH) which needed vitrectomy.
Protein Levels of ATF4, GRP78, and IL-6, MCP-1 in samples were evaluated using
enzyme-linked immunosorbent assay (ELISA). RESULTS: ELISA analysis revealed
significantly increased levels in both AqH and vitreous of ATF4 and GRP78 in eyes
affected with PDR compared to the controls (all p < 0.001). The mean
concentrations of IL-6, MCP-1 were also higher in both AqH and vitreous samples
from patients with PDR compared to those of IMH (all p < 0.001). (Independent
Student t-test, normality test followed with Skewness-Kurtosis Test). In
addition, correlations of ATF4 and GRP78 with inflammatory factors IL-6 and MCP-1
in subjects of patients were analyzed. No significant correlation between the AqH
concentrations of ATF4/IL-6 and ATF4/MCP-1 was detected in eyes of PDR patients
(r = 0.346, p = 0.072 and r = 0.275, p = 0.157). Significant correlations were
observed between AqH concentrations of GRP78/IL-6 (r = 0.724, p < 0.001),
GRP78/MCP-1 (r = 0.654, p < 0.001) in PDR patients. Significant correlations were
observed between vitreous concentrations of ATF4/IL-6 (r = 0.918, p < 0.001),
ATF4/MCP-1 (r = 0.921, p < 0.001), GRP78/IL-6 (r = 0.978, p < 0.001), GRP78/MCP-1
(r = 0.979, p < 0.001) in PDR patients. No significant correlations was observed
between AqH concentrations of ATF4/IL-6 (r = 0.187, p = 474), ATF4/MCP-1 (r =
0.240, p = 0.353), GRP78/IL-6 (r = 0.321, p = 0.209) and GRP78/MCP-1 (r = 0.169,
p = 0.516) in eyes of IMH patients. And also no significant correlation was
observed between vitreous concentrations of ATF4/IL-6 (r = 0.130, p = 0.563),
ATF4/MCP-1(r = 0.029, p = 0.897), GRP78/IL-6 (r = 0.078, p = 0.717), GRP78/MCP-1
(r = 0.005, p = 0.982) in IMH patients. (Pearson correlation coefficient (two
tailed)). CONCLUSIONS: Our results demonstrated that ATF4 and GRP78 may play an
important role in the pathogenesis of PDR and work in concert with inflammatory
cytokines IL-6 and MCP-1 in pathological process. ATF4 and GRP78 may be good
diagnostic biomarkers and new therapeutic targets for PDR. ABBREVIATIONS: ER
stress, endoplasmic reticulum stress; ATF4, activating transcription factor 4;
GRP78, glucose-regulated 78 kDa protein; AqH, aqueous humor; PDR, proliferative
diabetic retinopathy; IL-6, interleukin-6; MCP-1, monocyte chemoattractant
protein-1; IMH, idiopathic macular hole.
PMID- 28497988
TI - Till Porn Do Us Part? A Longitudinal Examination of Pornography Use and Divorce.
AB - As pornography use becomes more commonplace in the United States, and
increasingly so among younger cohorts, a growing literature is considering its
potential connection to key social and cultural institutions. The current study
examined the relationship between pornography use and one such institution:
marriage. We drew on three-wave longitudinal data from 2006 to 2014 General
Social Survey panel studies to determine whether married Americans' pornography
use predicted their likelihood of divorce over time and under what social
conditions. We employed a doubly robust strategy that combines entropy balancing
with logistic regression models. We found that the probability of divorce roughly
doubled for married Americans who began pornography use between survey waves (N =
2,120; odds ratio = 2.19), and that this relationship held for both women and
men. Conversely, discontinuing pornography use between survey waves was
associated with a lower probability of divorce, but only for women. Additional
analyses also showed that the association between beginning pornography use and
the probability of divorce was particularly strong among younger Americans, those
who were less religious, and those who reported greater initial marital
happiness. We conclude by discussing data limitations, considering potential
intervening mechanisms and the possibility of reverse causation, and outlining
implications for future research.
PMID- 28497989
TI - Focus on fluid reasoning: The relationship between fluid reasoning and the
Pattern of Strengths and Weaknesses model.
AB - The purpose of this paper is to examine the Fluid Reasoning Index of the Wechsler
Intelligence Test for Children, Fifth Edition (WISC-V), and determine how fluid
reasoning skills relate to academic skill acquisition in the classroom setting.
We also examine the myriad of ways within which learning and learning
disabilities can be defined. Also, we plan to examine a brief review of the
definition of a Specific Learning Disability and review some of the leading
theories related to the Pattern of Strengths and Weaknesses model.
PMID- 28497982
TI - Neuroprotection in Oxidative Stress-Related Neurodegenerative Diseases: Role of
Endocannabinoid System Modulation.
AB - SIGNIFICANCE: Redox imbalance may lead to overproduction of reactive oxygen and
nitrogen species (ROS/RNS) and subsequent oxidative tissue damage, which is a
critical event in the course of neurodegenerative diseases. It is still not fully
elucidated, however, whether oxidative stress is the primary trigger or a
consequence in the process of neurodegeneration. Recent Advances: Increasing
evidence suggests that oxidative stress is involved in the propagation of
neuronal injury and consequent inflammatory response, which in concert promote
development of pathological alterations characteristic of most common
neurodegenerative diseases. CRITICAL ISSUES: Accumulating recent evidence also
suggests that there is an important interplay between the lipid endocannabinoid
system [ECS; comprising the main cannabinoid 1 and 2 receptors (CB1 and CB2),
endocannabinoids, and their synthetic and metabolizing enzymes] and various key
inflammatory and redox-dependent processes. FUTURE DIRECTIONS: Targeting the ECS
to modulate redox state-dependent cell death and to decrease consequent or
preceding inflammatory response holds therapeutic potential in a multitude of
oxidative stress-related acute or chronic neurodegenerative disorders from stroke
and traumatic brain injury to Alzheimer's and Parkinson's diseases and multiple
sclerosis, just to name a few, which will be discussed in this overview.
Antioxid. Redox Signal. 29, 75-108.
PMID- 28497990
TI - Parental Mediation Regarding Children's Smartphone Use: Role of Protection
Motivation and Parenting Style.
AB - Parental mediation is a type of behavior that could protect children against the
negative uses and effects of smartphones. Based on protection motivation theory,
this research (a) predicted parental mediation based on parents' threat and
efficacy perceptions and (b) predicted threat and efficacy perceptions based on
parenting styles and parents' addiction to smartphone use. An online survey of
448 parents of fourth to sixth graders was conducted. Results showed that both
restrictive and active parental mediation were predicted by perceived severity,
response efficacy, and self-efficacy. With regard to parenting styles, (a)
authoritative parenting was positively related to perceived severity as well as
response- and self-efficacy, whereas (b) permissive parenting was negatively
related to self-efficacy. In addition, parents' addiction was a negative
predictor of perceived severity, but a positive predictor of perceived
susceptibility.
PMID- 28497991
TI - Medical Students' Professional Development as Educators Revealed Through
Reflections on Their Teaching Following a Students-as-Teachers Course.
AB - : Phenomenon: Teaching is an important part of the tri-partite mission of every
medical center. Although teaching often is given lower priority and recognition
as opposed to patient care and/or research, this activity for many physicians in
academic medicine ranks second to their patient care responsibilities. Medical
teacher training has traditionally been aimed at faculty and residents through
faculty development initiatives, continuing education for physicians at
professional conferences, formalized degree or certificate programs in education,
and residents as teachers programs. More recently medical schools have developed
medical-students-as-teachers programs, often offered as 4th-year electives, to
introduce learners to the theory of teaching and learning with appropriate
application in the clinical setting. Data on learner outcomes and students'
perceptions and experiences in these programs consist mostly of their
satisfaction after completing such a program. In this article we explore 4th-year
medical student trainees' experiences and emerging self-concepts as educators
during a teaching elective. APPROACH: The purpose of this project was to explore
students' reflections on their experiences in a 4th-year medical students-as
teachers course in their own words through their written self-assessment
narratives. We used qualitative content analysis to examine 96 trainees' self
reported, written reflective narratives of how they translated their students-as
teachers course experience into application by applying newly learned educational
theories, instructional strategies, and feedback skills while teaching novice
peers physical diagnosis skills. FINDINGS: Narratives revealed candid self
assessments and detailed descriptions of their experiences and what they valued
most from the course. Content analysis revealed nine key themes: using teaching
strategies for adult learning, preparing for class, modeling professionalism,
incorporating clinical correlations, exceeding course requirements, giving and
receiving feedback, providing mentoring, creating a positive learning climate,
and growing as educators. Insights: This study's results reveal how learners
perceive and translate their experiences in a teaching course, in terms of
incorporating particular knowledge or skills, valuing or displaying certain
professional behaviors, and gaining self-awareness and satisfaction from teaching
experiences. The findings of this study, specifically major themes from self
assessment narratives, provide us with a better understanding of medical
students' developing identities and emerging professional self-concept as
educators, specifically as experienced through a combination of formal teaching,
and applying education theories and strategies. Findings may be informative from
a program evaluation lens but also for faculty development initiatives related to
training medical teachers and the larger landscape of the emerging field of
Health Professions Education.
PMID- 28497992
TI - How does anxiety influence fluid reasoning?
AB - Does anxiety influence fluid reasoning, either negatively or positively? The
purpose of this article was to review much of the relevant current literature to
answer this question. An individual's ability to employ fluid reasoning to solve
novel problems must include the context of the circumstances, the individual's
unique set of cognitive resources, one's ability to utilize previously acquired
knowledge from similar situations, and to create a solution in a quick and
effective manner. Working memory and creativity are cognitive skill sets that
influence the efficiency and effectiveness of novel problem solving, while
anxiety can be a crippling factor for some. This article aims to discuss the role
of each of these factors the implementation of novel problem solving with a
special emphasis on the role of development during adolescence.
PMID- 28497994
TI - Temperamental Effortful Control Modulates Gender Differences in Late Positive
Potentials Evoked by Affective Pictures in Adolescents.
AB - We investigated whether effort control (EC) modulates gender differences in late
positive potential (LPP) evoked by affective pictures. We collected EEG data from
46 healthy adolescents while they viewed 90 affective pictures. Relative to
neutral pictures, boys showed larger LPP amplitudes for positive pictures
compared to girls while girls showed larger LPP amplitudes for negative pictures
compared to boys. Temperamental EC in boys negatively predicted LPP amplitudes
for positive pictures, whereas EC in girls negatively predicted LPP amplitudes
for negative pictures. These observations increase our understanding of the
relationship between EC and gender difference in electrocortical maturation.
PMID- 28497993
TI - Personal Variation in Preference for Sweetness: Effects of Age and Obesity.
AB - BACKGROUND: Use of nonnutritive sweeteners (NNSs), which provide sweet taste with
few to no calories, has increased, but data on whether children's hedonic
responses to NNSs differ from nutritive sugars or from adults' hedonic responses
are limited. METHODS: Most preferred levels of sucrose and the NNS sucralose were
determined via a forced-choice tracking procedure in 48 children, 7-14 years
(mean = 10 years), and 34 adults. Each participant also rated the liking of these
taste stimuli, as well as varying concentrations of aspartame on 3- and 5-point
facial hedonic scales. Anthropometric measures were obtained, and motives for
palatable food intake were assessed with the Palatable Eating Motives Scale
(PEMS, adults) and Kids PEMS. RESULTS: While use of the 3-point scale showed no
age-related differences in liking of sweeteners, the 5-point scale showed that
more children than adults liked higher concentrations of sucrose, sucralose, and
aspartame, and the tracking procedure showed that children most preferred higher
concentrations of sucrose and sucralose than adults. Regardless of age, sweet
preference did not differ between obese and nonobese participants and showed no
association with motives for eating palatable foods. Children's body mass index z
scores were positively associated with social and conformity motive scores for
eating palatable foods. CONCLUSION: Research should move beyond measures of
variation in sweet taste hedonics to include identifying motives, and the
physiological and psychological consequences of eating sweets, to shed light on
what children are more vulnerable to develop unfavorable eating habits,
increasing risk for obesity, and other diseases.
PMID- 28497995
TI - A rare case of small cell carcinoma of lung with intraventricular metastasis.
AB - Our case report involves a Chinese patient who was presented to our hospital with
the chief complaint of dizziness and double vision for one week. He was diagnosed
with small cell carcinoma of lung in the past. The patient undertook various test
at our hospital. His MR scan revealed an intraventricular metastasis from small
cell carcinoma of lung which is very rare. We have analyzed the clinical data of
this patient and related literature. We report this case to increase the
awareness of this rare metastasis of small cell carcinoma of lung.
PMID- 28497996
TI - Characterization of the Salmonella enterica Serotype Isangi Isolated from
Patients for the First Time in China.
AB - No studies have reported the isolation of serotype Salmonella Isangi from cases
of salmonellosis in mainland China. We investigated an outbreak of foodborne
disease with salmonella and collected the samples from the patients and surplus
foods. Salmonella strains were isolated and the serotype was identified according
to the Kauffmann-White scheme. The relatedness of the isolates was determined
using pulsed-field gel electrophoresis (PFGE) and whole genome sequencing (WGS).
Antimicrobial susceptibility was conducted by the broth microdilution method.
There were 74 diners in the case, 33 of which got ill, with an attack rate of
44.6% (33/74). A total of 24 samples were collected from the outbreak cases, six
Salmonella Isangi strains were isolated and susceptible to all tested drugs. PFGE
and WGS analysis suggested that the pathogen dissemination through a single or
limited vector(s), the steamed fish and mixed food (fry spicy chicken, braised
pork ribs, and goose leg), may be the source of infection or be cross
contaminated. We first report the characteristics of an outbreak and molecular
strain relatedness of Salmonella Isangi in mainland China.
PMID- 28497997
TI - Homophily in an Anonymous Online Community: Sociodemographic Versus Personality
Traits.
AB - In what traits do people interact with others who are similar to them in
completely anonymous online communication? Can those traits contribute to greater
exchange of opinion and information across the sociodemographic boundaries that
often limit interaction between social strata? To answer this question concerning
online homophily, we combined survey data on 7,287 users (aged 18 and above) of a
Korean online dating advice platform with their behavioral data from June 2015 to
August 2015 and explored whether advice exchange occurred between users with
similar sociodemographic and personality traits. On this platform, two types of
interactions occurred as follows: (1) responses to a randomly distributed problem
submitted by an advice seeker and (2) the seeker's indication of approval of any
of the responses given. The study found that (1) a receiver was more likely to
respond to problems submitted by seekers of a comparable age and that (2) seekers
were more likely to approve of a response if the seeker and receiver had similar
educational backgrounds. By contrast, homophily based on personality traits was
not observed even though some personality traits significantly affected the
likelihood of both response and approval. Our findings suggest that online
communication may breed sociodemographic homophily, whether based on age or
education, more than expected or intended while not easily fostering alternative
forms of homophily, such as personality homophily, which can potentially cut
across borders dividing sociodemographic groups.
PMID- 28497999
TI - Bullet fragment fiducials in stereotactic body radiotherapy as a bridge to
transplant for hepatocellular carcinoma.
PMID- 28498000
TI - Metastatic brain carotid body paraganglioma with endocrine activity: a case
report and literature review.
AB - A woman with hypertension and hyperglycemia was diagnosed a metastatic brain
carotid body paraganglioma. Her blood pressure, glucose, and norepinephrine were
normal after craniotomy. Although most carotid body tumors are benign, a few show
distant metastasis. This is the first reported case of intracerebral metastases
from a carotid body tumor.
PMID- 28497998
TI - Transcriptional reprogramming in cellular quiescence.
AB - Most cells in nature are not actively dividing, yet are able to return to the
cell cycle given the appropriate environmental signals. There is now ample
evidence that quiescent G0 cells are not shut-down but still metabolically and
transcriptionally active. Quiescent cells must maintain a basal transcriptional
capacity to maintain transcripts and proteins necessary for survival. This
implies a tight control over RNA polymerases: RNA pol II for mRNA transcription
during G0, but especially RNA pol I and RNA pol III to maintain an appropriate
level of structural RNAs, raising the possibility that specific transcriptional
control mechanisms evolved in quiescent cells. In accordance with this, we
recently discovered that RNA interference is necessary to control RNA polymerase
I transcription during G0. While this mini-review focuses on yeast model
organisms (Saccharomyces cerevisiae and Schizosaccharomyces pombe), parallels are
drawn to other eukaryotes and mammalian systems, in particular stem cells.
PMID- 28498001
TI - ABCE1: A special factor that orchestrates translation at the crossroad between
recycling and initiation.
AB - For many years initiation and termination of mRNA translation have been studied
separately. However, a direct link between these 2 isolated stages has been
suggested by the fact that some initiation factors also control termination and
can even promote ribosome recycling; i.e. the last stage where post-terminating
80S ribosomes are split to start a new round of initiation. Notably, it is now
firmly established that, among other factors, ribosomal recycling critically
requires the NTPase ABCE1. However, several earlier reports have proposed that
ABCE1 also somehow participates in the initiation complex assembly. Based on an
extended analysis of our recently published late-stage 48S initiation complex
from rabbit, here we provide new mechanistic insights into this putative role of
ABCE1 in initiation. This point of view represents the first structural evidence
in which the regulatory role of the recycling factor ABCE1 in initiation is
discussed and establishes a corner stone for elucidating the interplay between
ABCE1 and several initiation factors during the transit from ribosomal recycling
to formation of the elongation competent 80S initiation complex.
PMID- 28498002
TI - An observation study of the clinical evaluation of symptom relief and side
effects associated with taking ulipristal acetate (esmya) including its effect on
pre-menstrual syndrome.
AB - This was an observational study investigating the efficacy and side effects
associated with ulipristal acetate (UPA), a progesterone receptor modulator, and
the possible benefits to women who have co-existing pre-menstrual syndrome (PMS).
80 women returned a questionnaire on the bleeding, menstrual pain and side
effects, and changes on PMS were recorded. 67 women (84%) showed improvement in
their menses. 54 women (67%) became amenorrhoeic. Of those, 67% were within 10
days of commencing UPA. Menses returned in 33 amenorrhoeic women within 4 weeks
of stopping UPA. 58 women (70%) reported an improvement in their pain score but
41 women had a return of their pain after stopping UPA. The majority of the women
had no or infrequent side effects. 80% had demonstrable improvement in their PMS
symptoms. UPA is effective in controlling symptoms due to uterine fibroids with
infrequent side effects. Our data also showed new evidence of a concurrent
dramatic improvement in PMS in these women. Impact statement The observational
study explored the drug profile of ulipristal acetate (UPA), a selective
progesterone receptor modulator, which has been licenced as pre-treatment for
surgical therapies of fibroids since 2012. We aimed to investigate the efficiency
and side effects of UPA. Since the introduction of UPA in clinical practice,
there has yet to be a study looking at the drug profile outside a research
setting. We have also decided to investigate the effect of UPA on pre-menstrual
syndrome (PMS) in this group of women with symptomatic fibroids. As such this
case report should be of interest to a broad readership including those
interested in the medical management of symptomatic fibroids.
PMID- 28498003
TI - A Novel Approach to Assessing Professionalism in Preclinical Medical Students
Using Multisource Feedback Through Paired Self- and Peer Evaluations.
AB - : Phenomenon: Professionalism is integral to the role of the physician. Most
professionalism assessments in medical training are delayed until clinical
rotations where multisource feedback is available. This leaves a gap in student
assessment portfolios and potentially delays professional development. APPROACH:
A total of 246 second-year medical students (2013-2015) completed self- and peer
assessments of professional behaviors in 2 courses following a series of Team
Based Learning exercises. Correlation and regression analyses were used to
examine the alignment or misalignment in the relationship between the 2 types of
assessments. Four subgroups were formed based on observed patterns of initial
self- and peer assessment alignment or misalignment, and subgroup membership
stability over time was assessed. A missing data analysis examined differences
between average peer assessment scores as a function of selective
nonparticipation. FINDINGS: Spearman correlation demonstrated moderate to strong
correlation between self-assessments completed alone (no simultaneous peer
assessment) and self-assessments completed at the time of peer assessments (rho =
.59, p < .0001) but weak correlation between the two self-assessments and peer
assessments (alone: rho = .13, p < .013; at time of peer: rho = .21, p < .0001).
Generalized estimating equation models revealed that self-assessments done alone
(p < .0001) were a significant predictor of self-assessments done at the time of
peer. Course was also a significant predictor (p = .01) of self-assessment scores
done at the time of peer. Peer assessment score was not a significant predictor.
Bhapkar's test revealed subgroup membership based on the relationship between
self- and peer ratings was relatively stable across Time 1 and Time 2 assessments
(chi2 = 0.83, p = .84) for all but one subgroup; members of the subgroup with
initially high self-assessment and low peer assessment were significantly more
likely to move to a new classification at the second measurement. A missing data
analysis revealed that students who completed all self-assessments had
significantly higher average peer assessment ratings compared to students who
completed one or no self-assessments with a difference of -0.32, 95% confidence
interval [-0.48, -0.15]. Insights: Multiple measurements of simultaneous self-
and peer assessment identified a subgroup of students who consistently rated
themselves higher on professionalism attributes relative to the low ratings given
by their peers. This subgroup of preclinical students, along with those who
elected to not complete self-assessments, may be at risk for professionalism
concerns. Use of this multisource feedback tool to measure perceptual stability
of professionalism behaviors is a new approach that may assist with early
identification of at-risk students during preclinical years.
PMID- 28498004
TI - A Sequential Implementation Model for Workforce Development: A Case Study of
Medical Residency Training for Substance Use Concerns.
AB - PROBLEM: In graduate medical education, residency programs are often
educationally isolated from each other, with varying needs and patient
populations, so strategies are needed when attempting to implement training in
evidence-based practices across multiple residencies. INTERVENTION: Using
implementation science as a guide, we adapted a community development model to
sequentially implement an evidence-based intervention, Screening, Brief
Intervention, and Referral to Treatment (SBIRT) for alcohol and drug use
problems, across internal medicine, pediatrics, emergency medicine, psychiatry,
and obstetrics and gynecology residency programs. CONTEXT: A grant-funded
"executive" team coordinated the implementation, enrolled a new residency program
annually, and served as the consultative team to span the programs. The team was
attentive to aligning implementation with the needs of each program. To assist in
planning, the team included a program champion 1 year prior to SBIRT
implementation to provide the opportunity to develop resources and work with
peers. We evaluated this model through an implementation science lens using a
case study approach that included interviews and quantitative tabulation of
products and resident perceptions. OUTCOME: We successfully instituted SBIRT
training in all 5 residency programs through the use of a supported local
champion model. Teams developed 90 curricular products and had 57 presentations
and publications. Residents reported satisfaction with the SBIRT activities.
Champions reported that SBIRT was a useful approach and that they gained valuable
knowledge and relationships from working with the executive team when designing
learning materials appropriate for their residency. Champions successfully
incorporated SBIRT into routine clinical practice. LESSONS LEARNED: Having a
strong team to support subsequent SBIRT champions was essential for
implementation. The champions needed financial support to have the necessary time
to implement training. The strategy of building a peer network across programs
was critical for sustaining the implementation. Collecting and sharing resources
aided the champions in developing their materials.
PMID- 28498005
TI - School Protective Factors and Substance Use Among Lesbian, Gay, and Bisexual
Adolescents in California Public Schools.
AB - PURPOSE: The majority of studies examining substance use among lesbian, gay, and
bisexual (LGB) youth have focused on a wide array of risk factors (e.g.,
victimization). Few studies have explored the protective role of schools. This
study aims to fill this gap in the literature and inform programs aimed at
reducing substance use among LGB youth. More specifically, this study explores
the extent to which school connectedness and support from teachers and other
adults at school are associated with substance use among LGB youth in school and
within the past 30 days. METHODS: A secondary analysis of the 2013-2015
California Healthy Kids Survey (CHKS) was conducted to examine associations
between school protective factors (i.e., school connectedness and adult support)
and substance use among LGB youth, above and beyond a key risk factor, school
victimization. The study outcomes were past 30-day and in-school use of
cigarettes, alcohol, marijuana, inhalants, prescription pain medication, and
other illegal drugs. RESULTS: Overall, school connectedness and school adult
support were associated with lower odds of substance use. For example, higher
levels of school connectedness were associated with 22% decreased odds of past 30
day inhalant use (adjusted odds ratio [AOR] = 0.78; 95% confidence interval [CI]
= 0.72-0.86), and 25% decreased odds of past 30-day prescription pain medication
use (AOR = 0.75; 95% CI = 0.69-0.82). Higher levels of adult support in school
were also associated with 17% decreased odds of marijuana use on school property
in the past 30 days (AOR = 0.83; 95% CI = 0.77-0.91). CONCLUSION: The results
indicate a need for substance use prevention programs that integrate school
connectedness and adult support in school.
PMID- 28498006
TI - Serum YKL-40 as a potential biomarker of inflammation in psoriasis.
AB - OBJECTIVE: YKL-40 is an inflammatory glycoprotein associated with
atherosclerosis, cardiovascular disease, diabetes or metabolic syndrome which are
common comorbidities in psoriasis. The aim of the study was to assess serum YKL
40 level in psoriasis and elucidate possible associations with disease activity,
inflammatory or metabolic parameters and treatment. METHODS: A total of 37
individuals with active plaque-type psoriasis and 15 healthy controls were
enrolled. Blood samples were collected before and after 2 weeks of therapy. Serum
YKL-40 concentrations were evaluated by enzyme-linked immunosorbent assay
(ELISA). The results were correlated with Psoriasis Area and Severity Index
(PASI), body mass index (BMI), inflammatory and biochemical markers, lipid
profile and topical therapy. RESULTS: Median YKL-40 serum levels were
significantly increased in psoriatic patients in comparison to the controls (p <
.0001). No significant correlations between investigated protein and metabolic
parameters as BMI (p = .19), glucose (p = .32) nor lipids levels were found.
Significant positive relation with CRP (p = .003) or alanine aminotransferase (p
= .04) and no correlation with PASI (p = .2) were noted. Serum YKL-40 level
remained unchanged (p = .5) after topical treatment, despite clinical
improvement. CONCLUSIONS: YKL-40 might be a biomarker of psoriasis and
inflammation in psoriatic patients, but not a reliable indicator of metabolic
conditions, severity of psoriasis nor efficacy of the treatment.
PMID- 28498007
TI - Are Hybrid Liver Resections Truly Minimally Invasive? A Propensity Score Matching
Analysis.
AB - BACKGROUND: Hybrid liver resection is considered a modality of minimally invasive
surgery; however, there are doubts regarding loss of benefits of laparoscopy due
to the use of an auxiliary incision. We compared perioperative results of
patients undergoing hybrid * open and hybrid * pure laparoscopic resections.
METHODS: Consecutive patients undergoing liver resection between June 2008 and
January 2016 were studied. Study groups were compared after propensity score
matching (PSM). RESULTS: Six hundred forty-four resections were included in the
comparative analysis: 470 open, 120 pure laparoscopic, and 54 hybrids. After PSM,
54 patients were included in each group. Hybrid * open: hybrid technique had
shorter operative time (319.5 +/- 108.6 * 376.2 +/- 155.8 minutes, P = .033),
shorter hospital stay (6.0 +/- 2.7 * 8.1 +/- 5.6 days, P = .001), and lower
morbidity (18.5% * 40.7%, P = .003). Hybrid * pure laparoscopic: hybrid group had
lower conversion rate (0% * 13%, P = .013). There was no difference regarding
estimated blood loss, transfusion rate, hospital stay, complications, or
mortality. CONCLUSIONS: Hybrid resection has better perioperative results than
the open approach and is similar to pure laparoscopy. The hybrid technique should
be considered a minimally invasive approach.
PMID- 28498008
TI - Spatial Orientation and Navigation in Children With Perinatal Stroke.
AB - As a focal injury in an otherwise healthy child, perinatal stroke provides a
clinical model of developmental brain plasticity. In this study, we report
evidence that children with perinatal periventricular venous infarcts perform as
well as control children on a video game that tests navigation abilities. In
addition, children with a history of perinatal arterial strokes overcame initial
deficits in navigation performance after additional practice. These findings lend
support to the hypothesis that a complex cognitive skill dependent on a
distributed neural network with prolonged maturation, such as navigation, may
demonstrate resilience after early brain injury.
PMID- 28498009
TI - 'I feel better when...': An analysis of the memory-experience gap for peoples'
estimates of the relationship between health behaviours and experiences.
AB - OBJECTIVE: People often overestimate how strongly behaviours and experiences are
related. This memory-experience gap might have important implications for health
care settings, which often require people to estimate associations, such as "my
mood is better when I exercise". This study examines how subjective correlation
estimates between health behaviours and experiences relate to calculated
correlations from online reports and whether subjective estimates are associated
with engagement in actual health behaviour. DESIGN: Seven-month online study on
physical activity, sleep, affect and stress, with 61 online assessments. MAIN
OUTCOME MEASURES: University students (N = 168) retrospectively estimated
correlations between physical activity, sleep, positive affect and stress over
the seven-month study period. RESULTS: Correlations between experiences and
behaviours (online data) were small (r = -.12-.14), estimated correlations
moderate (r = -.35-.24). Correspondence between calculated and estimated
correlations was low. Importantly, estimated correlations of physical activity
with stress, positive affect and sleep were associated with actual engagement in
physical activity. CONCLUSION: Estimation accuracy of relations between health
behaviours and experiences is low. However, association estimates could be an
important predictor of actual health behaviours. This study identifies and
quantifies estimation inaccuracies in health behaviours and points towards
potential systematic biases in health settings, which might seriously impair
intervention efficacy.
PMID- 28498010
TI - From play to problem solving to Common Core: The development of fluid reasoning.
AB - How and when does fluid reasoning develop and what does it look like at different
ages, from a neurodevelopmental and functional perspective? The goal of this
article is to discuss the development of fluid reasoning from a practical
perspective of our children's lives: from play to problem solving to Common Core
Curriculum. A review of relevant and current literature supports a connection
between movement, including movement through free play, and the development of
novel problem solving. As our children grow and develop, motor routines can
become cognitive routines and can be evidenced not only in games, such as chess,
but also in the acquisition and demonstration of academic skills. Finally, this
article describes the connection between novel problem solving and the demands of
the Common Core Curriculum.
PMID- 28498011
TI - Factors Associated with Antiretroviral Therapy Adherence Among Transgender Women
Receiving HIV Medical Care in the United States.
AB - PURPOSE: We examined factors associated with antiretroviral therapy (ART)
adherence among transgender women living with HIV (TWLWH). METHODS: We used
combined data from the 2009 to 2013 cycles of Medical Monitoring Project, an HIV
surveillance system designed to produce nationally representative estimates of
the characteristics of HIV-infected adults receiving HIV medical care in the
United States. Rao-Scott chi-square tests and multivariable logistic regression
were used to identify factors associated with dose adherence (defined as taking
100% of prescribed ART doses in the past 3 days). RESULTS: Among TWLWH who
reported current ART use, an estimated 80.5% self-reported dose adherence.
Multivariable factors independently associated with lower (<100%) dose adherence
were younger age (30-39 vs. 40 and over), not having health insurance coverage,
depression, lower self-efficacy to take medication as prescribed, and having
greater than one daily ART dose. CONCLUSION: Our findings suggest several ways to
potentially improve ART adherence of TWLWH including tailoring efforts to address
the needs of TWLWH under age 40, increasing access to health insurance coverage,
addressing mental health morbidities, building skills to improve medication
adherence self-efficacy, and simplifying ART regimens when possible.
PMID- 28498012
TI - Unmet expectations of medications and care providers among patients with heart
failure assessed to be poorly adherent: results from the Chronic Heart Failure
Intervention to Improve MEdication Adherence (CHIME) study.
AB - BACKGROUND: Ineffective medication management contributes to repeated
hospitalisation and death among patients with heart failure. The meaning ascribed
to medications and the influence of meaning on how patients manage medications is
unknown. The purpose of this study was to explore the meaning and expectations
associated with medication use in high-risk, non-adherent patients with heart
failure. METHODS AND RESULTS: Patients ( n=265) with heart failure were screened
for adherence to prescribed medication using the Morisky medication adherence
scale (MMAS). Patients (MMAS score <6; n=44) participated in semistructured
interviews, analysed using qualitative content analysis. Of 17 initial themes
(223 representative segments), the overarching theme 'unmet expectations'
consisted of two subthemes 'working to be heard' by professionals and
'resignation' to both the illness and medications. Patients' expectations were
challenged by unexpected work to communicate with providers in general (72
representative segments), and specifically regarding medications (118
representative segments) and feelings of resignation regarding the medication
regimen (33 representative segments). CONCLUSIONS: These findings suggest that
unmet expectations contribute to poor medication management. Improved listening
and communication by providers, to establish a common understanding and plan for
managing medications may strengthen patient beliefs, resolve feelings of
resignation and improve patients' ability to manage medications effectively.
PMID- 28498014
TI - Self-efficacy as a predictor of treatment outcome in an outpatient eating
disorder program.
AB - This prospective pilot study examined the relationship between self-efficacy and
treatment outcome in an adult outpatient eating disorder program. Data from 59
eating disorder outpatients were collected, including measures of self-efficacy,
eating disorder symptom severity, negative emotions (depression, anxiety, and
stress), body mass index, and duration of illness. Hierarchical regression was
used to examine the impact of baseline self-efficacy, and early treatment changes
in self-efficacy (i.e., baseline to 6 weeks), on end-of-treatment (EoT) eating
disorder symptom severity and treatment dropout. Early change in self-efficacy
during the course of treatment was found to predict EoT symptom severity when
controlling for confounding variables. Furthermore, baseline self-efficacy was
found to predict treatment dropout, but not end-of-treatment symptom severity.
This is the first study (using a validated scale) to show that self-efficacy, and
early changes in self-efficacy, may be an important predictor of treatment
outcome for eating disorder outpatients. Implications and suggestions for future
research are discussed.
PMID- 28498013
TI - Disparities in Counseling Female Cancer Patients for Fertility Preservation.
AB - BACKGROUND: Female cancer patients who are exposed to gonadotoxic chemotherapy
are at risk of future infertility. Research suggests that disparities in
fertility preservation counseling (FPC) may exist. Previous research is limited
by recall bias; therefore, this study examined objective electronic medical chart
data regarding FPC at an academic medical center. MATERIALS AND METHODS: This
study included reproductive-aged women (18-45 years old) with a diagnosis of
breast, gynecological, or hematological cancer and who were exposed to a
gonadotoxic chemotherapeutic agent from 2009 to 2013. Chi-square and logistic
regression analyses were utilized to analyze disparities in FPC. RESULTS: Two
hundred fifty-nine women met the study criteria. One hundred eighty-one women
were diagnosed with breast cancer, 52 with hematological cancer, and 26 with
gynecological cancer. 160/259 (62%) women had documented counseling for fertility
preservation (FP), 60 (23%) women were not counseled as counseling was determined
to be "not applicable," 16 (6%) women were not counseled and no explanation was
given for the lack of counseling, and counseling was not documented in 23 (9%)
charts. Age, marital status, and racial/ethnic background were related to
counseling status. Patients with gynecological or hematological cancer were more
likely to be counseled than other patients. Logistic regression results
demonstrated that FPC was largely driven by cancer diagnosis. CONCLUSIONS:
Although cancer diagnosis was the greatest predictor of FPC, disparities were
evident in the counseling of female cancer patients for FP treatment. Equality in
counseling female patients for FP treatment is imperative to reduce the risk of
emotional harm and future infertility.
PMID- 28498015
TI - Tracking the Functional Development of the Corpus Callosum in Children Using
Behavioral and Evoked Potential Interhemispheric Transfer Times.
AB - Visual functions requiring interhemispheric transfer exhibit a long developmental
trajectory up to age 12, which might be constrained by corpus callosum
maturation. Here, we use electrophysiological and behavioral crossed-uncrossed
differences (CUDs) in a visual Poffenberger paradigm to estimate the
interhemispheric transfer time (IHTT)-a measure of corpus callosum maturation-in
7-year-old children and adults. Adults' electrophysiological CUDs were faster
than 7-year-olds'. Behavioral CUDs did not differ and proved to be unreliable in
a 6-month follow-up test. These findings suggest that the corpus callosum still
undergoes development at the age of 7 that can only reliably be traced with
neuroscientific methods.
PMID- 28498016
TI - Accelerated vernalization response by an altered PHD-finger protein in
Arabidopsis.
AB - Vernalization is a response to the winter cold to acquire the competence to
flower in next spring. VERNALIZATION INSENSITIVE 3 (VIN3) is a PHD-finger protein
that binds to modified histones in vitro. VIN3 is induced by long-term cold and
is necessary for Polycomb Repression Complex 2 (PRC2)-mediated tri-methylation of
Histone H3 Lysine 27 (H3K27me3) at the FLC locus in Arabidopsis. An alteration in
the PHD-finger domain of VIN3 changes the binding specificity of the PHD-finger
domain of VIN3 in vitro and results in an accelerated vernalization response in
vivo. The acceleration in vernalization response is achieved by increased
enrichments of VIN3 and tri-methylation of Histone H3 Lysine 27 (H3K27me3) at the
FLC locus without invoking the increased enrichment of Polycomb Repressive
Complex 2. This result indicates that the binding specificity of the PHD-finger
domain of VIN3 plays a role in mediating a proper vernalization response in
Arabidopsis. Furthermore, this work shows a potential that the alteration of PHD
finger domains could be applied to alter various developmental processes in
plants.
PMID- 28498017
TI - Dietary Supplements as Surrogate of Mediterranean Diet in Healthy Smoking
Subjects.
AB - The interventions to slow aging, favoring active life expectancy, represent the
new perspectives in ageing investigation. Some mechanisms that delay or prevent
the onset of aging pathologies have been identified. Between them, a healthy
lifestyle seems to reduce many risk factors. In particular, eating habits
represent the most concrete, low-cost way to act on aging process. Mediterranean
diet has received much attention since its antioxidant and anti-inflammatory
effects have been consistently demonstrated. Unfortunately, many people follow a
Western diet, poor in phytochemicals that represent the main source of beneficial
effects of this dietary pattern. So, supplements administration should be
considered, especially in subjects exposed to high level of oxidative stress and
inflammation. So, we tested the properties of a commercial food supplement
containing a series of plant polyphenols in combination with caffeine, bioperine
(black pepper extract), and selenium in smoking healthy volunteers. Fifty
participants have been recruited and hematochemical analyses and biochemistry
tests have been performed, before and after 60 days of supplement intake.
Thirteen subjects dropped out of the study. At the end of the intervention, the
variation of inflammatory and oxidant markers has been evaluated, measuring
urinary isoprostanes, serum advanced glycation end products, and oxidized low
density lipoproteins. The results showed that this supplement exhibits promising
antioxidant and anti-inflammatory responses, especially in women, highlighting
the role of supplementation in certain groups of subjects, for the control of
oxidative stress as well as inflammatory status. So, its intake should be useful
in delaying the onset of age-related diseases.
PMID- 28498018
TI - Full Robotic Colorectal Resections for Cancer Combined With Other Major Surgical
Procedures: Early Experience With the da Vinci Xi.
AB - BACKGROUND: The da Vinci Xi has been developed to overcome some of the
limitations of the previous platform, thereby increasing the acceptance of its
use in robotic multiorgan surgery. METHODS: Between January 2015 and October
2015, 10 patients with synchronous tumors of the colorectum and others abdominal
organs underwent robotic combined resections with the da Vinci Xi. Trocar
positions respected the Universal Port Placement Guidelines provided by Intuitive
Surgical for "left lower quadrant," with trocars centered on the umbilical area,
or shifted 2 to 3 cm to the right or to the left, depending on the type of
combined surgical procedure. RESULTS: All procedures were completed with the full
robotic technique. Simultaneous procedures in same quadrant or left quadrant and
pelvis, or left/right and upper, were performed with a single docking/single
targeting approach; in cases of left/right quadrant or right quadrant/pelvis, we
performed a dual-targeting operation. No external collisions or problems related
to trocar positions were noted. No patient experienced postoperative surgical
complications and the mean hospital stay was 6 days. CONCLUSIONS: The high
success rate of full robotic colorectal resection combined with other surgical
interventions for synchronous tumors, suggest the efficacy of the da Vinci Xi in
this setting.
PMID- 28498019
TI - Severe human parechovirus type 3 infection in adults associated with
gastroenteritis in their children.
PMID- 28498021
TI - Successful treatment of Becker's Nevus with long-pulsed 1064-nm Nd:YAG and 755-nm
alexandrite laser and review of the literature.
AB - BACKGROUND: Becker's Nevus is an aesthetically troublesome condition secondary to
hyperpigmentation and hypertrichosis. Although several lasers have been employed
with varying degrees of success, the exact devices and treatment parameters have
yet to be elucidated. OBJECTIVE: To assess the combination Nd:YAG and alexandrite
laser as a safe and efficacious treatment for Becker's Nevus. METHODS: In a 20
year-old Fitzpatrick Skin Type IV male, a Becker's Nevus was treated with six
sessions of long-pulsed 1064 nm Nd:YAG laser at six-week intervals followed by
five sessions of long-pulsed 755 nm alexandrite laser at three-month intervals.
RESULTS: This patient experienced a significant reduction in both
hyperpigmentation and hypertrichosis after these treatment sessions. No serious
adverse events were reported. CONCLUSION: This case supports the use of
combination long-pulsed 1064 nm laser and 755 nm laser as a safe and efficacious
treatment for Becker's Nevus.
PMID- 28498020
TI - Cell cycle genes are activated earlier than respiratory genes during release of
grapevine buds from endodormancy.
AB - Single-bud cuttings of Vitis vinifera L exposed to forced growing conditions were
used to investigate the involvement of phytohormones, abscisic acid (ABA), auxin
(Aux) and cytokinin (CK) in the release of buds from the ED and in bud-sprouting.
This artificial system imitates and hastens the natural sprouting that occurs in
spring. Temporal expression analysis of genes related to phytohormones synthesis,
showed an early drop in the expression of ABA biosynthesis gene that preceded an
increase in Aux and CK biosynthesis genes. Bud-break is headed by the activation
of all structures of the latent bud, especially the differentiation of the
inflorescence and the development of the early stages of floral organs.
Therefore, resumption of cell division and increases in respiration are essential
for the activation of the bud. Temporal expression analysis of the cell cycle and
respiration genes indicate that an increase in cell division go before the
increase in respiration. These results, together with results indicating that the
cell cycle genes are upregulated by Aux and CK, suggest that the events before
the bud-break, start with a reduction in ABA content, followed by an increase in
the content of Aux and CK, which activates the machinery of the cell cycle, which
eventually would cause an increase in respiration.
PMID- 28498022
TI - Thyroid hormone analogs for the treatment of dyslipidemia: past, present, and
future.
AB - OBJECTIVE: Treatment of dyslipidemia is a major burden for public health. Thyroid
hormone regulates lipid metabolism by binding the thyroid hormone receptor (TR),
but the use of thyroid hormone to treat dyslipidemia is not indicated due to its
deleterious effects on heart, bone, and muscle. Thyroid hormone analogs have been
conceived to selectively activate TR in the liver, thus reducing potential side
effects. METHODS: The authors searched the PubMed database to review TR and the
action of thyromimetics in vitro and in animal models. Then, all double-blind,
placebo controlled trials that analyzed the use of thyroid hormone analog for the
treatment of dyslipidemia in humans were included. Finally, the ongoing research
on the use of TR agonists was searched, searching the US National Institutes of
Health Registry and the WHO International Clinical Trial Registry Platform
(ICTRP). RESULTS: Thyromimetics were tested in humans for the treatment of
dyslipidemia, as a single therapeutic agent or as an add-on therapy to the
traditional lipid-lowering drugs. In most trials, thyromimetics lowered total
cholesterol, low-density lipoprotein cholesterol, and triglycerides, but their
use has been associated with adverse side-effects, both in pre-clinical studies
and in humans. CONCLUSIONS: The use of thyromimetics for the treatment of
dyslipidemia is not presently recommended. Future possible clinical applications
might include their use to promote weight reduction. Thyromimetics might also
represent an interesting alternative, both for the treatment of non-alcoholic
steatohepatitis, and type 2 diabetes due to their positive effects on insulin
sensitivity. Finally, additional experimental and clinical studies are needed for
a better comprehension of the effect(s) of a long-term therapy.
PMID- 28498023
TI - Physical and/or Sexual Abuse Is Associated with Increased Psychological and
Emotional Distress Among Transgender Women.
AB - PURPOSE: Transgender women have consistently reported elevated rates of lifetime
physical and sexual abuse. This study examined the associations between reported
physical and/or sexual abuse and symptoms of psychological and emotional distress
among a sample of urban, high-risk transgender women. METHODS: From June 2005
through July 2012, 99 transgender women enrolled in a Comprehensive Risk
Counseling and Services program in Hollywood, CA. Seemingly unrelated regression
equations (SURE) were used to simultaneously regress psychiatric symptom reports
on participant sociodemographic characteristics and self-reported history of
physical/sexual abuse. RESULTS: Participants were African American/Black (33.3%),
Caucasian/White (28.3%), or Hispanic/Latina (24.2%). Average age was 35 years
(standard deviation [SD] = 9), and 37.4% of participants self-reported an HIV
positive status. Most (84.9%) participants reported experiencing physical or
sexual abuse at some point in their lifetime, and symptoms of psychological and
emotional distress (as measured by the Brief Symptom Inventory) among those who
reported abuse were more severe than those observed in cisgender psychiatric in
patient populations. After controlling for participant sociodemographics, prior
experience of physical and/or sexual abuse was associated with significantly
increased psychological and emotional distress across all measured symptom
domains except psychoticism [chi2(9) = 17.56; p < 0.05]. CONCLUSION: Given these
associations as well as the high prevalence of physical and/or sexual abuse among
transgender women, mental health professionals and social service providers
working with this population should be sensitive to the abuse history and mental
health needs of the transgender women with whom they work.
PMID- 28498024
TI - A prospective risk assessment of informal carers' medication administration
errors within the domiciliary setting.
AB - Increasingly, medication is being administered at home by family and friends of
the care-recipient. This study aims to identify and analyse risks associated with
potential drug administration errors made by informal carers at home. We mapped
medication administration at home with a multidisciplinary team that included
carers, health care professionals and patients. Evidence-based risk-analysis
methodologies were applied: Healthcare Failure Modes and Effect Analysis (HFMEA),
Systematic Human Error Reduction and Prediction Analysis (SHERPA) and Systems
Theoretic Accident Model and Processes (STAMP). The process of administration
comprises seven sub-processes. Thirty-four possible failure modes were identified
and six of these were rated as high risk. These highlighted that medications may
be given with a wrong dose, stored incorrectly, not discontinued as instructed,
not recorded, or not ordered on time, and often caused by communication and
support problems. Combined risk analyses contributed unique information helpful
to better understand the medication administration risks and causes within
homecare. Practitioner Summary: Increasingly, medication is being administered at
home by family and friends of the care-recipient. This study identifies risks
associated with potential drug administration errors made by informal carers at
home through consensus-based quantitative techniques. The different analyses
contribute unique information helpful to better understand the administration
risks and causes.
PMID- 28498025
TI - Understanding meaning in life interventions in patients with advanced disease: A
systematic review and realist synthesis.
AB - BACKGROUND: Among patients with advanced disease, meaning in life is thought to
enhance well-being, promote coping and improve the tolerance of physical
symptoms. It may also act as a buffer against depression and hopelessness. As
yet, there has been no synthesis of meaning in life interventions in which
contextual factors, procedures and outcomes are described and evaluated. AIMS: To
identify meaning in life interventions implemented in patients with advanced
disease and to describe their context, mechanisms and outcomes. DESIGN:
Systematic review according to Preferred Reporting Items for Systematic Reviews
and Meta-Analyses guidelines and realist synthesis of meaning in life
interventions using criteria from the Realist And Meta-narrative Evidence
Syntheses: Evolving Standards project. DATA SOURCES: The CINAHL, PsycINFO, PubMed
and Web of Science databases were searched. RESULTS: A total of 12 articles were
included in the systematic review, corresponding to nine different interventions.
Five articles described randomized controlled trials, two were qualitative
studies, two were commentaries or reflections, and there was one pre-post
evaluation, one exploratory study and one description of a model of care.
Analysis of context, mechanisms and outcomes configurations showed that a core
component of all the interventions was the interpersonal encounter between
patient and therapist, in which sources of meaning were explored and a sense of
connectedness was re-established. Meaning in life interventions were associated
with clinical benefits on measures of purpose-in-life, quality of life, spiritual
well-being, self-efficacy, optimism, distress, hopelessness, anxiety, depression
and wish to hasten death. CONCLUSION: This review provides an explanatory model
of the contextual factors and mechanisms that may be involved in promoting
meaning in life. These approaches could provide useful tools for relieving
existential suffering at the end of life.
PMID- 28498026
TI - The Development of Palliative Care in Argentina: A Mapping Study Using Latin
American Association for Palliative Care Indicators.
AB - BACKGROUND: The Latin American Association for Palliative Care (ALCP) developed
10 indicators to monitor the development of palliative care. The indicators have
been applied across Latin American countries but have not been used internally.
OBJECTIVE: The aims of this study were to document the development of palliative
care in Argentina at the national and provincial levels by using a selection of
the indicators developed by the ALCP and identify the difficulties and needs of
healthcare professionals working in palliative care. This is the first study to
apply the indicators intranationally. METHODS: This was a cross-sectional pilot
study based on two questionnaires with representatives from each province, one
workshop, and telephone conversations to corroborate the collected data. These
data were used to calculate a preselection of eight ALCP indicators covering four
main areas of development: education, policy, service delivery, and medication. A
total of 30 participants took part in the study. RESULTS: The application of the
ALCP indicators at the province level led to the identification of inequalities
in the development and distribution of services across the country. The provinces
in the north-west were identified as the region with the greatest need for
development. The main difficulties for healthcare professionals were lack of
national service registries, certified palliative care specialties, and
opportunities for continuous training. DISCUSSION: The ALCP indicators are useful
tools for mapping palliative care development within countries. Further work
needs to be carried out to increase their specificity and integrate them in
policy design and service delivery.
PMID- 28498027
TI - Asthma and early herniated intervertebral disc disease.
AB - BACKGROUND: The etiology of herniated intervertebral disc (HIVD) disease in
children and adolescents is multifactorial and not merely related to disc
degeneration. Therefore, in the present study, we investigated the relationship
between young asthma patients and the risk of early HIVD disease in a population
under 30 years of age. METHODS: Data from the National Health Insurance Research
Database (NHIRD) of Taiwan were used to conduct a retrospective longitudinal
cohort study. The study cohort comprised 23,470 patients with asthma (asthma
group) and 23,470 patients without asthma (non-asthma group), who were selected
through frequency matching on the basis of sex, age, and the index year. The
study patients were followed until HIVD disease occurrence, withdrawal from the
National Health Insurance program, or 31 December 2013. Cox proportional hazards
regression analysis was conducted to assess the risk of HIVD disease in the
asthma group after adjustment for sex, age, and comorbidities. RESULTS: After
adjustment for sex, age, and comorbidities, the asthma group had a 1.69-fold (95%
confidence interval [CI] = 1.29-2.23) higher risk of HIVD disease than did the
non-asthma group. In addition, the asthma group had a higher risk of cervical and
lumbar HIVD diseases than did the non-asthma group (adjusted hazard ratio [HR] =
2.38; 95% CI = 1.25-4.57 and adjusted HR = 1.56; 95% CI = 1.15-2.12,
respectively). CONCLUSIONS: Young patients with asthma are at a significantly
higher risk of early cervical or lumbar HIVD disease.
PMID- 28498028
TI - miR-337 can be a key negative regulator in melanoma.
AB - Incidence of melanoma is increasing annually worldwide. There remains a lack of
suitable treatment methods which can significantly improve the 5-year survival
rates of patients. It is established that micro RNAs (miRNAs) have important
roles in the diagnosis and treatment of cancer. MiR-337 had been reported to
regulate the development of variety of cancers, as a cancer suppressive factor.
In our research we found that miR-337 had a lower expression in melanoma than
adjacent tissues. The patients who had a lower miR-337 also got a worse survival.
MiR-337 could target STAT3 to regulate the occurrence and development of
melanoma. In summary, our findings suggest that the miR-337/STAT3 axis may serve
as a potential target for the treatment of melanoma.
PMID- 28498029
TI - Is one day off sufficient for re-adaptation to a daytime routine after two
consecutive nights of work?
AB - Fast rotation three-shift working schedules are common in the medical field in
Taiwan. This study investigated whether 24 h off is sufficient for re-adaptation
to a daytime routine after working two night shifts (NSs) by comparing changes in
cognitive function, anxiety state and objectively measured sleep propensity
between those working two NSs followed by 24 h off (n = 21, 2NS-off) and an off
duty group (n = 21, OD). The results showed that nurses in the 2NS-off group were
less alert and had decreased visual attention performance and executive function
ability than the OD group during the daytime. One day off appeared to be
insufficient to adapt back to a daytime shift after two NSs. Further studies are
warranted to investigate whether a longer sequence of consecutive NSs (e.g. four
NSs) followed by two days off is suitable for a fast rotation three-shift work
schedule to allow for optimal performance throughout the next daytime shift.
Practitioner Summary: The medical field in Taiwan mandates at least 24 h off
between night and day shifts, but this appears to be insufficient for re-adapting
to a daytime shift after two night shifts. A longer sequence of consecutive night
shifts followed by two days off may be more suitable.
PMID- 28498030
TI - Prevalence of anemia and its influence on hospital readmissions and emergency
department visits in outpatients with heart failure.
AB - BACKGROUND: Anemia is a frequent comorbidity in patients with heart failure.
However, the incidence of anemia in patients with heart failure varies widely,
and there is limited evidence on the association between anemia and
rehospitalization and on the health consequences of anemia in patients with heart
failure. AIMS: We aimed to identify the prevalence of anemia and its influence on
hospital readmissions and emergency department visits in outpatients with heart
failure. METHODS: This cross-sectional study included 284 patients with heart
failure diagnosed at outpatient cardiology clinics at a tertiary care university
hospital in Cheonan, South Korea. We obtained socio-demographic and clinical
information, including frequency of readmissions and emergency department visits,
using face-to-face interviews and medical record reviews. RESULTS: The prevalence
of anemia, defined based on World Health Organization guidelines, was 39.1% among
patients with heart failure. Anemia was significantly more prevalent among
patients with one or more re-admissions or emergency department visits compared
with patients with no history of hospital re-admissions or emergency department
visits (42.7% vs. 13.9% ( p = 0.001) and 55.1% vs. 34% ( p = 0.002)
respectively). Anemia increased the risk of hospital readmission (odds ratio
=8.04, 95% confidence interval, 2.19-29.54) and emergency department visit (odds
ratio=2.37, 95% confidence interval, 1.22-4.60) in patients with heart failure.
CONCLUSION: It is imperative that patients with heart failure presenting with
anemia undergo appropriate nursing assessment and intervention. Future
prospective studies targeting interventions to improve anemia are required to
determine whether anemia influences readmission rates and emergency department
visits.
PMID- 28498031
TI - Diagnosis and Management of Malignant Melanoma in Store-and-Forward
Teledermatology.
AB - BACKGROUND: Published studies have led to concern that store-and-forward
teledermatology (SFT) diagnosis and management of melanomas may be inferior to
face-to-face (FTF) dermatology care. INTRODUCTION: To ascertain the frequency of
correctly managed and diagnosed melanomas within a population of veterans in
Veterans Integrated Service Network 20 SFT. MATERIALS AND METHODS: We conducted a
retrospective chart review of 7,960 veterans seen by SFT between July 1, 2009 and
December 31, 2011. RESULTS: Of the 61 veterans that met inclusion and exclusion
criteria, 45 (74%) melanomas were correctly diagnosed and 57 (93%) were correctly
managed. DISCUSSION: Diagnostic and management accuracy of SFT is comparable to
FTF. Incorrect diagnosis or management of melanomas did not prove to have
significant consequences for patient care. Cases subject to analysis of this
study are not demographically representative of the general population.
CONCLUSION: Diagnosis and management of melanoma in SFT is comparable to FTF
care.
PMID- 28498032
TI - The Experiences of Reciprocity among Filipino Older Adults in Canada:
Intergenerational, Transnational, and Community Considerations.
AB - This article illustrates the concept of reciprocity in the context of immigrant
families. It recommends that definition of reciprocity account for exchanges
beyond the immediate family, and render visible the simultaneous location of
older people as care recipients and providers, and care arrangements across
generations, borders, community, and time. Adopting a critical ethnographic study
on the aging and care experiences of older Filipinos in Canada, this article
analyzes data from extended observations and in-depth semi-structured interviews
with 18 older people, 6 adult children, and 13 community stakeholders. Findings
highlight the unique configurations of care among the Filipino community whereby
older people engage in care exchange as active participants across
intergenerational, transnational, and fictive kin networks.
PMID- 28498033
TI - Development and Characterization of Novel Monoclonal Antibodies Against Human
DNAM-1.
AB - DNAM-1 (CD226) is an activating immunoreceptor expressed on lymphocytes and
myeloid cells. CD155 and CD112 are the ligands for DNAM-1. DNAM-1 plays an
important role in tumor immunity mediated by CD8+ T cells and NK cells. Moreover,
the interaction of DNAM-1 with the ligands contributed to the development of
acute graft versus host disease (GVHD) and treatment with anti-DNAM-1 monoclonal
antibodies (mAb) dramatically improved acute GVHD in a mouse model, suggesting
that DNAM-1 may be a good molecular target for therapy to acute GVHD in human. In
this study, we generated and characterized five novel clones of anti-human DNAM-1
mAbs, named TX94, TX95, TX96, TX107, and TX108. Among these mAbs, TX94 is a
unique neutralizing mAb that most efficiently blocked the interaction between
DNAM-1 and CD155. Furthermore, TX94 inhibited NK cell-mediated cytotoxicity
against a tumor cell line and suppressed CD8+ T cell proliferation mediated by
allogeneic mixed lymphocyte reaction. Thus, TX94 may be useful for molecular
therapy targeting DNAM-1.
PMID- 28498034
TI - Assessment of Resident Physicians' Communicator and Collaborator Competencies by
Interprofessional Clinicians: A Mixed-Methods Study.
AB - : Phenomenon: As we move toward competency-based medical education, greater
emphasis is being placed on assessing a more comprehensive skill set, including
the ability to communicate and collaborate effectively in the workplace.
Nonphysician members on interprofessional (IP) teams have valuable perspectives
on actual resident performance and are often not adequately engaged in the
provision of feedback to residents. Based on the educational theories of
collaborative evaluation and social constructivism, this research examined the
ability of IP clinicians to provide feedback to residents. The aim of this study
was to examine IP clinicians' perceptions of their ability to provide formative
feedback, through their observations and assessments of developmental pediatric
residents, compared to physician supervisors on the rotation, and to
qualitatively explore potential barriers to the feedback process from their
perspective. APPROACH: This explanatory, sequential mixed-methods design study
first examined which and how many of the CanMEDS Communicator and Collaborator
training objectives (N = 40) were considered to be observable and assessable by
IP clinicians and physicians. A comparison of the mean number of objectives that
were observed and practically assessed by (a) each group (IP clinicians vs.
physicians) and (b) clinical service teams during the core developmental
pediatrics rotations, were examined using independent t tests. Second, a thematic
qualitative analysis of focus groups was used to develop a contextual
understanding of the factors that influenced this process. Data were analyzed
using three levels of open coding and descriptive qualitative analysis
techniques. FINDINGS: Physicians reported they could observe (M = 33.3, SD = 5.2,
83.3%) and assess (M = 31.5, SD = 7.3, 79%) a larger number of objectives
compared to the IP clinician group (M = 24.7, SD = 8.6, 61.8% and M = 20.3, SD =
10.6, 51%, respectively). There were no differences between the clinical service
teams (i.e., preschool/school-age and pediatric rehabilitation). The objective
that was most observable and assessable by the IP clinicians was "Demonstrates a
respectful attitude towards other colleagues and members of an interprofessional
team." Four themes identified by the IP clinicians provided more in-depth
qualitative information: (a) assessment requires more than simple observation,
(b) assumptions and indirect observation influence assessment, (c) clinic culture
and structure shapes observation and assessment, and (d) specific assessment
criteria are required by IP clinicians. Insights: IP clinicians have the desire
and ability to provide formative feedback to residents. Formalized processes with
specific evaluation criteria would facilitate meaningful feedback from IP
clinicians in the assessment of residents as they journey toward competence.
PMID- 28498036
TI - Combination radiotherapy and cantharidin inhibits lung cancer growth through
altering tumor infiltrating lymphocytes.
AB - This study aimed to detect the effect of combination radiotherapy and cantharidin
on lung cancer growth. We found that combination therapy with radiotherapy and
cantharidin was more effective in inhibiting the tumor growth than radiotherapy
or cantharidin alone. It decreased the percentage of CD4+ Tregs and enhanced the
percentage of CD8+ T cells, CD4+ Teff cells when comparing to that of single
treatment. Combination therapy promoted a great increase in double producing CD8+
T cells and CD4+ Teff cells in tumor infiltrating lymphocytes. Overexpression of
CTLA4 reversed the inhibitory action of combination treatment on cancer growth.
Our data suggest that combining radiotherapy and cantharidin may have synergistic
effects in driving tumor rejection by increasing T-cell infiltration,
proliferation and cytokine production.
PMID- 28498035
TI - Assessment of older adults' satisfaction with adult protective services
investigation and assistance.
AB - This study examined elder self-neglect client satisfaction with services provided
by an Adult Protective Services (APS) program. A total of 77 community-dwelling
older adults with APS-substantiated self-neglect responded to the standardized
and widely used 8-item Client Satisfaction Questionnaire. Approximately 75% of
the participants reported being satisfied with the overall services. They felt
that the services provided were responsive to their need(s) and helped them deal
with their problem(s). Greater than 80% responded that they would refer a friend,
would utilize APS in the future if necessary, and were at least satisfied with
the amount of help received. The extent to which their needs were met received
the lowest satisfaction scores. Future studies are needed to examine elder self
neglect client satisfaction in relation to specific services.
PMID- 28498037
TI - Do parental decision-making patterns predict compliance with use of child booster
seats?
AB - Booster seat use for 4-9 year olds remains the lowest of all age groups in many
countries. The objective of this study is to examine whether parents' decision
making patterns, as measured by the Melbourne Decision Making Questionnaire,
relate to car booster seat use. Israeli parents of 4-7 years old children (n =
398) answered a questionnaire about car safety and decision-making habits. Ninety
per cent of parents reported having a booster seat; 70.5% reported consistent
booster seat use in general and on short drives during the last month (booster
seat use compliance index). Greater compliance index was positively related to a
vigilant decision-making pattern, passenger compliance with rear seat belts and
families with fewer children. Lower booster seat use compliance index was
associated with buck-passing decision-making pattern. Health professionals and
policy-makers should take into account parents' habitual decision-making patterns
when designing interventions for car booster seat compliance.
PMID- 28498038
TI - Determination of Metal Elements in Wine Using Laser-Induced Breakdown
Spectroscopy (LIBS).
AB - We developed a method for sensitive elemental analysis of wines using laser
induced breakdown spectroscopy (LIBS). In order to overcome the inefficiency of
direct ablation of bulk wine (an organic liquid), a thin layer of wine residue
was prepared on a metallic target according to an appropriated heating procedure
applied to an amount of liquid wine dropped on the target surface. The obtained
ensemble was thus ablated. Such a sample preparation procedure used a very small
volume of 2 mL of wine and took only 30 min without reagent or solvent. The
results show the detection of tens of metal and non-metal elements including
majors (Na, Mg, K, Ca), minors, and traces (Li, B, Si, P, Ti, Mn, Fe, Cu, Zn, Rb,
Sr, Ba, and Pb) in wines purchased from local supermarkets and from different
production places in France. Commercially available wines were then spiked with
certified standard solutions of Ti and Fe. Three series of laboratory reference
samples were thus prepared using three different wines (a red wine and a white
wine from a same production region and a red wine from another production region)
with concentrations of Ti and Fe in the range of 1-40 mg/L. Calibration graphs
established with the spiked samples allowed extracting the figures-of-merit
parameters of the method for wine analysis such as the coefficient of
determination ( R2) and the limits of detection and quantification (LOD and LOQ).
The calibration curves built with the three wines were then compared. We studied
the residual matrix effect between these wines in the determination of the
concentrations of Ti and Fe.
PMID- 28498039
TI - Seduction and the self: movements through precarity, race and sexuality in
Japanese host clubs.
AB - In this article, I build on the notion of precarity to argue that Japanese host
clubs are sites in which a particular kind of intimacy and sense of 'belonging'
are produced. The analysis highlights host clubs as necessary spaces among many
in the precarious economy and as important venues for the production of
subjectivity for the male hosts (both migrant and Japanese) as well as for the
migrant women who frequent these establishments. In particular, host clubs
provide a lucrative employment opportunity for young men - particularly young men
who are migrants from the rural parts of Japan or the Philippines (and often
Japanese-Filipino young men) who are trying to make a living in the context of
what has been characterised as 'precarious Japan'. I draw on extended
ethnographic fieldwork to show how the host clubs, though a part of the
precarious economy, provide sites of home and belonging for both hosts and their
clients.
PMID- 28498040
TI - Pivotal Role of Non-cardiomyocytes in Electromechanical and Therapeutic Potential
of Induced Pluripotent Stem Cell-Derived Engineered Cardiac Tissue.
AB - Although engineered cardiac tissues (ECTs) derived from induced pluripotent stem
cells (iPSCs) are promising for myocardial regenerative therapy, the appropriate
ratio of cardiomyocytes to non-cardiomyocytes is not fully understood. Here, we
determined whether ECT-cell content is a key determinant of its
structure/function, thereby affecting ECT therapeutic potential for advanced
heart failure. Scaffold-free ECTs containing different ratios (25%, 50%, 70%, or
90%) of iPSC-derived cardiomyocytes were generated by magnetic-activated cell
sorting by using cardiac-specific markers. Notably, ECTs showed synchronized
spontaneous beating when cardiomyocytes constituted >=50% of total cells, with
the electrical-conduction velocity increasing depending on cardiomyocyte ratio;
however, ECTs containing 90% cardiomyocytes failed to form stable structures.
ECTs containing 25% or 50% cardiomyocytes predominantly expressed collagen and
fibronectin, whereas ECTs containing 70% cardiomyocytes predominantly expressed
laminin and exhibited the highest contractile/relaxation properties. Furthermore,
transplantation of ECTs containing 50% or 70% cardiomyocytes into a rat chronic
myocardial infarction model led to a more profound functional recovery as
compared with controls. Notably, transplanted ECTs showed electrical
synchronization with the native heart under Langendorff perfusion. Collectively,
these results indicate that the quantity of non-cardiomyocytes is critical in
generating functional iPSC-derived ECTs as grafts for cardiac-regeneration
therapy, with ECTs containing 50-70% cardiomyocytes exhibiting stable structures
and increased cardiotherapeutic potential.
PMID- 28498041
TI - Sense of Community on Twitter and Instagram: Exploring the Roles of Motives and
Parasocial Relationships.
AB - Although research has explored the ways in which people form virtual communities
to converse about media figures, television shows, and similar topics, little
research has examined the link between virtual communities and the parasocial
relationships (PSRs) that are often the focus of these conversations and users'
experiences in those virtual communities. We examined sense of community (SOC) on
Twitter and Instagram as a function of users' motives for use and users' PSR on
the sites. In addition to examining the relative importance of different motives
for using Twitter and Instagram, we predicted that PSR would mediate the
association between motives for use and SOC. Results of an online survey revealed
that Instagram users (n = 276) reported stronger social interaction motives than
did Twitter users (n = 223). Social interaction and expressive information
sharing motives were directly positively associated with SOC for users of both
sites. Instagram users also exhibited indirect effects of expressive information
sharing and companionship motives on SOC, through PSR. These findings suggest
potentially influential differences between Twitter and Instagram, particularly
regarding the role of PSR in fostering a general SOC.
PMID- 28498042
TI - What Predicts Facebook Addiction?
PMID- 28498043
TI - Pain and Pain Management Among University Students: Online Survey and Web-Based
Education.
AB - Pain is common among university students. Unrelieved pain has adverse impacts on
their quality of life. In this study, a pain management Web site was developed to
distribute an online survey and provide Web-based pain education to university
students. Participants were recruited from eight universities in Hong Kong using
snowball sampling. The online survey included 37 items examining pain situations,
pain management strategies, knowledge about self-medication, and demographic data
of the participants. A total of 387 students participated and over 90 percent of
them reported pain in the past 6 months. Around one-third of participants did not
take any action to manage their pain. Pharmacological method was the most common
strategy for students to relieve pain (37.2 percent). The use of over-the-counter
(OTC) drug for pain relief was high (n = 214). However, OTC drug knowledge score
was significantly higher among health-related group than nonhealth-related group
(p < 0.001). There were 188 students who also read the Web-based pain education
and completed the evaluation on its usefulness. Nonhealth-related students
reported significantly higher scores of self-perceived usefulness for the online
education than the health-related students (p < 0.001). Findings suggested the
need to consider the service users' background when developing online education
program in the future.
PMID- 28498045
TI - Problematic Video Game Play and ADHD Traits in an Adult Population.
AB - This study examined the relationship between problematic video game play (PVGP),
video game usage, and attention deficit hyperactivity disorder (ADHD) traits in
an adult population. A sample of 205 healthy adult volunteers completed the Adult
ADHD Self-Report Scale (ASRS), a video game usage questionnaire, and the Problem
Video Game Playing Test (PVGT). A significant positive correlation was found
between the ASRS and the PVGT. More specifically, inattention symptoms and time
spent playing video games were the best predictors of PVGP. No relationship was
found between frequency and duration of play and ADHD traits. Hyperactivity
symptoms were not associated with PVGP. Our results suggest that there is a
positive relationship between ADHD traits and problematic video game play. In
particular, adults with higher level of self-reported inattention symptoms could
be at higher risk of PVGP.
PMID- 28498046
TI - Social Media Propagation of Content Promoting Risky Health Behavior.
AB - While social media have been found useful in providing social support and health
information, they have also been home to content advocating risky health
behavior. This study focused on how content defending and even celebrating
anorexia as a lifestyle are circulated among social media users, and investigates
the characteristics that promote wide propagation of such messages. We captured
anorexia-related content on Tumblr, a popular blog for talking about eating
disorders, during a one-month period. Among the 35,432 posts collected, we
examined the most highly propagated posts and coded them for message
characteristics. Our findings revealed that posts in which the source of a
narrative ("testimony") was identified (was either from an anorexic poster or
about another's anorexia) and which were positive toward the pro-anorexia
perspective were more likely to be propagated on Tumblr. In addition, posts
containing content that references an anorexic person and contains an affective
tone were more likely to be propagated. We also found that underweight bodies and
bodies with a high degree of exposure were associated with propagation of posts.
The present study suggested practical implications by focusing on the
characteristics of highly propagated but potentially harmful content in social
media.
PMID- 28498047
TI - Fatal Attractions: Attachment to Smartphones Predicts Anthropomorphic Beliefs and
Dangerous Behaviors.
AB - As technology's presence grows increasingly concrete in global societies, so too
do our relationships with the devices we keep close at hand from day to day.
Whereas research has, in the past, framed smartphone addiction in terms of
possessional attachment, the present research hypothesizes that anxious
smartphone attachment stems from human attachment, in which Anxiously attached
individuals may be more likely to generalize their anxious attachment style to
communication devices. In the present study, we found support for this hypothesis
and showed that anxious smartphone attachment predicts (1) anthropomorphic
beliefs, (2) reliance on-or "clinginess" toward-smartphones, and (3) a seemingly
compulsive urge to answer one's phone, even in dangerous situations (e.g., while
driving). Taken together, we seek to provide a theoretical framework and
methodological tools to identify the sources of technology attachment and those
most at risk of engaging in dangerous or inappropriate behaviors as a result of
attachment to ever-present mobile devices.
PMID- 28498049
TI - The paradox of recognition: hijra, third gender and sexual rights in Bangladesh.
AB - Hijra, the iconic figure of South Asian gender and sexual difference, comprise a
publicly institutionalised subculture of male-bodied feminine-identified people.
Although they have existed as a culturally recognised third gender for a very
long time, it is only recently that hijra have been legally recognised as a third
gender in several South Asian countries. This paper focuses on the transformation
of this long-running cultural category of third gender into a legal category of
third gender in Bangladesh, showing that the process of legal recognition has
necessitated a simultaneous mobilisation of a discourse of disability in the
constitution of hijra as citizens worthy of rights. While the international
community views the recognition of a third gender as a progressive socio-legal
advance in the obtaining of sexual rights in a Muslim majority Bangladesh,
locally, hijra are understood as a special group of people born with 'missing' or
ambiguous genitals delinked from desire. Furthermore, what was previously a trope
of disfigurement based on putative genital status has now been transformed into a
discourse of disability, a corollary to which several interest groups, namely the
civil society, the state, international community and hijra themselves, have all
been party.
PMID- 28498050
TI - Quinone oxidoreductase 2 is involved in haustorium development of the parasitic
plant Phtheirospermum japonicum.
AB - The family Orobanchaceae includes many parasitic plant species. Parasitic plants
invade host vascular tissues and form organs called haustoria, which are used to
obtain water and nutrients. Haustorium formation is initiated by host-derived
chemicals including quinones and flavonoids. Two types of quinone oxidoreductase
(QR) are involved in signal transduction leading to haustorium formation; QR1
mediates single-electron transfers and QR2 mediates 2-electron transfers. In the
facultative parasite Triphysaria versicolor, QR1 is involved in haustorium
induction signaling, while this role is played by QR2 in the model plant
Phtheirospermum japonicum. Our results suggest that there is functional
diversification in haustorium signaling molecules among different species of the
Orobanchaceae.
PMID- 28498051
TI - Editor's presentation.
PMID- 28498052
TI - Decreased expression of MMP-9 in CD8+ cells in placenta with severe preeclampsia.
AB - We compared the number of CD4-positive (CD4+) and CD8-positive (CD8+) cells in
severe and non-severe preeclampsia (PE), and in normal pregnancy. We also
evaluated the expression of matrix metalloproteinase 9 (MMP-9) in CD4+ and CD8+
cells. Immunohistochemistry for CD4+ and CD8+ was performed on the decidua
basalis of 15 severe and 13 non-severe PE women and compared to decidual tissue
of 19 normal pregnancies (control group). Co-expression of MMP-9 with CD8+ and
CD4+ cells was determined by double immunofluorescence staining. The median
number of CD8+ cells/mm2 was significantly lower for the severe PE group than for
the normal pregnancy group, as was the number of CD4+ cells and MMP-9+CD8+ cells.
No statistical difference was found between the non-severe PE group and the
normal pregnancy group. The significant decrease of CD4+, CD8+ and MMP-9+CD8+
cells at the fetal-maternal interface only in the severe PE group suggests that
immunological disorders play a role in the pathophysiology of severe PE.
PMID- 28498054
TI - First clinical use of stereotaxy in humans: the key role of x-ray localization
discovered by Gaston Contremoulins.
AB - Although attempts to develop stereotactic approaches to intracranial surgery
started in the late 19th century with Dittmar, Zernov, and more famously, Horsley
and Clarke, widespread use of the technique for human brain surgery started in
the second part of the 20th century. Remarkably, a significant similar surgical
procedure had already been performed in the late 19th century by Gaston
Contremoulins in France and has remained unknown. Contremoulins used the
principles of modern stereotaxy in association with radiography for the first
time, allowing the successful removal of intracranial bullets in 2 patients. This
surgical premiere, greatly acknowledged in the popular French newspaper
L'Illustration in 1897, received little scientific or governmental interest at
the time, as it emanated from a young self-taught scientist without official
medical education. This surgical innovation was only made possible financially by
popular crowdfunding and, despite widespread military use during World War I,
with 37,780 patients having benefited from this technique for intra- or
extracranial foreign bodies, it never attracted academic or neurosurgical
consideration. The authors of this paper describe the historical context of
stereotactic developments and the personal history of Contremoulins, who worked
in the department of experimental physiology of the French Academy of Sciences
led by Etienne-Jules Marey in Paris, and later devoted himself to radiography and
radioprotection. The authors also give precise information about his original
stereotactic tool "the bullet finder" ("le chercheur de projectiles") and its key
concepts.
PMID- 28498053
TI - Autism Behavior Inventory: A Novel Tool for Assessing Core and Associated
Symptoms of Autism Spectrum Disorder.
AB - OBJECTIVE: Autism Behavior Inventory (ABI) is a new measure for assessing changes
in core and associated symptoms of autism spectrum disorder (ASD) in participants
(ages: 3 years-adulthood) diagnosed with ASD. It is a web-based tool with five
domains (two ASD core domains: social communication, restrictive and repetitive
behaviors; three associated domains: mental health, self-regulation, and
challenging behavior). This study describes design, development, and initial
psychometric properties of the ABI. METHODS: ABI items were generated following
review of existing measures and inputs from expert clinicians. Initial ABI scale
contained 161 items that were reduced to fit a factor analytic model, retaining
items of adequate reliability. Two versions of the scale, ABI-full (ABI-F; 93
items) and ABI-short version (ABI-S; 36 items), were developed and evaluated for
psychometric properties, including validity comparisons with commonly used
measures. Both scales were administered to parents and healthcare professionals
(HCPs) involved with study participants. RESULTS: Test-retest reliability
(intraclass correlation coefficient [ICC] = 0.79) for parent ratings on ABI was
robust and compared favorably to existing scales. Test-retest correlations for
HCP ratings were generally lower versus parent ratings. ABI core domains and
comparison measures strongly correlated (r >= 0.70), demonstrating good
concurrent validity. CONCLUSIONS: Overall, ABI demonstrates promise as a tool for
measuring change in core symptoms of autism in ASD clinical studies, with further
validation required.
PMID- 28498055
TI - The intercostal nerve as a target for diagnostic biopsy.
AB - OBJECTIVE Peripheral nerve biopsy is a useful tool in diagnosing peripheral
neuropathies. Sural and gracilis nerves have become the most common targets for
nerve biopsy. However, the yield of sural nerve biopsy is limited in patients who
have motor neuropathies, and gracilis nerve biopsy presents technical challenges
and increased complications. The authors propose the intercostal nerve as an
alternative motor nerve target for biopsy. METHODS A total of 4 patients with
suspected peripheral neuropathies underwent intercostal nerve biopsy at the
authors' institution. A rib interspace that is inferior to the pectoralis muscle
and anterior to the anterior axillary line is selected for the procedure.
Generally the lower intercostal nerves (i.e., T7-11) are targeted. An incision is
made over the inferior aspect of the superior rib at the chosen interspace. Blunt
dissection is carried down to the neurovascular bundle and the nerve is isolated,
ligated, and cut to send for pathological examination. RESULTS The average
operative time for all cases was 73 minutes, with average blood loss of 8 ml.
Biopsy results from 1 patient exhibited axonopathy, and the other 3 patients
demonstrated axonopathy with demyelination. There were no short- or long-term
postoperative complications. None of the patients reported sensory or motor
deficits related to the biopsy at 6 weeks postoperatively. CONCLUSIONS The
intercostal nerve can be an alternative target for biopsy, especially in patients
with predominantly motor neuropathies, due to its mixed sensory and motor fibers,
straightforward anatomy, minimal risk of serious sensory deficits, and no risk of
motor impairment.
PMID- 28498056
TI - Risk factors for surgical site infections and assessment of vancomycin powder as
a preventive measure in patients undergoing first-time cranioplasty.
AB - OBJECTIVE Craniectomy is often performed to decrease intracranial pressure
following trauma and vascular injuries. The subsequent cranioplasty procedures
may be complicated by surgical site infections (SSIs) due to prior trauma,
foreign implants, and multiple surgeries through a common incision. Several
studies have found that intrawound vancomycin powder (VP) is associated with
decreased risk of SSIs after spine operations. However, no previously published
study has evaluated the effectiveness of VP in cranioplasty procedures. The
purpose of this study was to determine whether intrawound VP is associated with
decreased risk of SSIs, to evaluate VP's safety, and to identify risk factors for
SSIs after cranioplasty among patients undergoing first-time cranioplasty.
METHODS The authors conducted a retrospective cohort study of adult patients
undergoing first-time cranioplasty for indications other than infections from
January 1, 2008, to July 31, 2014, at an academic health center. Data on
demographics, possible risk factors for SSIs, and treatment with VP were
collected from the patients' electronic health records. RESULTS During the study
period, 258 patients underwent first-time cranioplasties, and 15 (5.8%) of these
patients acquired SSIs. Ninety-two patients (35.7%) received intrawound VP (VP
group) and 166 (64.3%) did not (no-VP group). Patients in the VP group and the no
VP group were similar with respect to age, sex, smoking history, body mass index,
and SSI rates (VP group 6.5%, no-VP group 5.4%, p = 0.72). Patients in the VP
group were less likely than those in the no-VP group to have undergone
craniectomy for tumors and were more likely to have an American Society of
Anesthesiologists physical status score > 2. Intrawound VP was not associated
with other postoperative complications. Risk factors for SSI from the bivariable
analyses were diabetes (odds ratio [OR] 3.65, 95% CI 1.07-12.44), multiple
craniotomy procedures before the cranioplasty (OR 4.39, 95% CI 1.47-13.18), prior
same-side craniotomy (OR 4.73, 95% CI 1.57-14.24), and prosthetic implants (OR
4.51, 95% CI 1.40-14.59). The multivariable analysis identified prior same-side
craniotomy (OR 3.37, 95% CI 1.06-10.79) and prosthetic implants (OR 3.93, 95% CI
1.15-13.40) as significant risk factors for SSIs. After adjusting for potential
confounders, patients with SSIs were more likely than those without SSIs to be
readmitted (OR 7.28, 95% CI 2.07-25.60). CONCLUSIONS In this study, intrawound VP
was not associated with a decreased risk of SSIs or with an increased risk of
complications. Prior same-side craniotomy and prosthetic implants were risk
factors for SSI after first-time cranioplasty.
PMID- 28498057
TI - Stereotactic radiosurgery alone or combined with embolization for brain
arteriovenous malformations: a systematic review and meta-analysis.
AB - OBJECTIVE Embolization of brain arteriovenous malformations (AVMs) prior to
stereotactic radiosurgery (SRS) has been reported to negatively affect
obliteration rates. The goal of this systematic review and meta-analysis was to
compare the outcomes of AVMs treated with embolization plus SRS (E+SRS group) and
those of AVMs treated with SRS alone (SRS group). METHODS A literature review was
performed using PubMed to identify studies with 10 or more AVM patients and
obliteration data for both E+SRS and SRS groups. A meta-analysis was performed to
compare obliteration rates between the E+SRS and SRS groups. RESULTS Twelve
articles comprising 1716 patients were eligible for analysis. Among the patients
with radiological follow-up data, complete obliteration was achieved in 48.4% of
patients (330/681) in the E+SRS group compared with 62.7% of patients (613/978)
in the SRS group. A meta-analysis of the pooled data revealed that the
obliteration rate was significantly lower in the E+SRS group (OR 0.51, 95% CI
0.41-0.64, p < 0.00001). Symptomatic adverse radiation effects were observed in
6.6% (27/412 patients) and 11.1% (48/433 patients) of the E+SRS and SRS groups,
respectively. The annual post-SRS hemorrhage rate was 2.0%-6.5% and 0%-2.0% for
the E+SRS and SRS groups, respectively. The rates of permanent morbidity were 0%
6.7% and 0%-13.5% for the E+SRS and SRS groups, respectively. CONCLUSIONS
Arteriovenous malformation treatment with combined embolization and SRS is
associated with lower obliteration rates than those with SRS treatment alone.
However, this comparison does not fully account for differences in the initial
AVM characteristics in the E+SRS group as compared with those in the SRS group.
Further studies are warranted to address these limitations.
PMID- 28498058
TI - Endoscopic endonasal resection of the odontoid process: clinical outcomes in 34
adults.
AB - OBJECTIVE Treatment of odontoid disease from a ventral corridor has consisted of
a transoral approach. More recently, the endoscopic endonasal approach (EEA) has
been used to access odontoid pathology. METHODS A retrospective review was
conducted of patients who underwent an EEA for odontoid pathology from 2004 to
2013. During our analysis, the mean follow-up duration was 42.6 months (range 1
80 months). Patient outcomes, complications, and postoperative swallowing
function were assessed either by clinic visit or phone contact. RESULTS Thirty
four patients underwent an EEA for symptomatic odontoid pathology. The most
common pathology treated was basilar invagination (n = 17). Other pathologies
included odontoid fractures, os odontoideum, and metastatic carcinoma. The mean
patient age was 71.5 years. Thirty-one patients underwent a posterior fusion. All
34 patients experienced stability or improvement in symptoms and all had
successful radiographic decompression. The overall complication rate was 76%.
Nearly all of these complications were transient (86%) and the overall
complication rate excluding mild transient dysphagia was only 44%. Twenty-one
patients (62%) suffered from transient postoperative dysphagia: 15 cases were
mild, transient subjective dysphagia (6 of whom had documented preoperative
dysphagia), whereas 6 other patients required tube feedings for decreased oral
intake, malnutrition, and dysphagia in the perioperative setting (5 of these
patients had documented preoperative dysphagia). Sixteen patients had documented
preoperative dysphagia and 6 of these had lower cranial nerve dysfunction.
Postoperatively, 6 (37.5%) of 16 patients with preoperative dysphagia and 4 (67%)
of 6 with lower cranial nerve dysfunction had significant dysphagia/respiratory
complications. Eighteen patients had no documented preoperative dysphagia and
only 2 had significant postoperative dysphagia/respiratory complications (11%).
The rates of these complications in patients without preoperative dysphagia were
lower than in those with any preoperative dysphagia (p = 0.07) and especially
those with preexisting lower cranial neuropathies (p = 0.007). Dysphagia was also
significantly more common in patients who underwent occipitocervical fixation
(19/26, 73%) than in patients who underwent cervical fusion alone or no fusion
(2/8, 25%; p = 0.02). All patients with perioperative dysphagia had improved at
follow-up and all patients were tolerating oral diets. No patient suffered from
velopalatal insufficiency. Two patients had intraoperative CSF leaks. One of
these patients underwent a negative exploratory surgery for a questionable
postoperative CSF leak. One patient developed infection in the resection bed
requiring debridement and antibiotics. One patient died 8 days following surgery
from an unknown cause. The 90-day perioperative mortality rate was 2.9%.
CONCLUSIONS A completely EEA can be performed for compressive odontoid disease in
all cases of neoplastic, degenerative, or invaginative atlantoaxial disease with
satisfactory outcomes and low morbidity. Transient perioperative dysphagia and
respiratory complications are common, usually as an exacerbation and reflection
of underlying disease or occipitocervical fusion rather than the EEA, emphasizing
the importance of avoiding transoral surgery.
PMID- 28498059
TI - Oligodendroglioma resection: a Surveillance, Epidemiology, and End Results (SEER)
analysis.
AB - OBJECTIVE The available evidence suggests that the clinical benefits of extended
resection are limited for chemosensitive tumors, such as primary CNS lymphoma.
Oligodendroglioma is generally believed to be more sensitive to chemotherapy than
astrocytoma of comparable grades. In this study the authors compare the survival
benefit of gross-total resection (GTR) in patients with oligodendroglioma
relative to patients with astrocytoma. METHODS Using the Surveillance,
Epidemiology, and End Results (SEER) Program (1999-2010) database, the authors
identified 2378 patients with WHO Grade II oligodendroglioma (O2 group) and 1028
patients with WHO Grade III oligodendroglioma (O3 group). Resection was defined
as GTR, subtotal resection, biopsy only, or no resection. Kaplan-Meier and
multivariate Cox regression survival analyses were used to assess survival with
respect to extent of resection. RESULTS Cox multivariate analysis revealed that
the hazard of dying from O2 and O3 was comparable between patients who underwent
biopsy only and GTR (O2: hazard ratio [HR] 1.06, 95% confidence interval [CI]
0.73-1.53; O3: HR 1.18, 95% CI 0.80-1.72). A comprehensive search of the
published literature identified 8 articles without compelling evidence that GTR
is associated with improved overall survival in patients with oligodendroglioma.
CONCLUSIONS This SEER-based analysis and review of the literature suggest that
GTR is not associated with improved survival in patients with oligodendroglioma.
This finding contrasts with the documented association between GTR and overall
survival in anaplastic astrocytoma and glioblastoma. The authors suggest that
this difference may reflect the sensitivity of oligodendroglioma to chemotherapy
as compared with astrocytomas.
PMID- 28498060
TI - Correlation between reduction in microvascular transit time after superficial
temporal artery-middle cerebral artery bypass surgery for moyamoya disease and
the development of postoperative hyperperfusion syndrome.
AB - OBJECTIVE Hyperperfusion syndrome (HPS) is a notable complication that causes
various neurological symptoms after superficial temporal artery (STA)-middle
cerebral artery (MCA) bypass surgery for moyamoya disease (MMD). The authors used
intraoperative indocyanine green (ICG) videoangiography to measure the change in
microvascular transit time (MVTT) after bypass surgery. An analysis was then
conducted to identify the correlation between change in MVTT and presence of
postoperative HPS. METHODS This study included 105 hemispheres of 81 patients
with MMD who underwent STA-MCA single bypass surgery between January 2010 and
January 2015. Intraoperative ICG videoangiography was performed before and after
bypass surgery. The MVTT was calculated from the ICG time intensity curve
recorded in the pial arterioles and venules. Multivariate logistic regression
analysis was conducted to test the effect of multiple variables, including the
change in MVTT after bypass surgery, on postoperative HPS. RESULTS Postoperative
HPS developed in 28 (26.7%) of the 105 hemispheres operated on. MVTT was reduced
significantly after bypass surgery (prebypass 5.34 +/- 2.00 sec vs postbypass
4.12 +/- 1.60 sec; p < 0.001). The difference between prebypass and postbypass
MVTT values, defined as DeltaMVTT, was significantly greater in the HPS group
than in the non-HPS group (2.55 +/- 2.66 sec vs 0.75 +/- 1.78 sec; p < 0.001).
Receiver operating characteristic curve analysis revealed that the optimal cutoff
point of DeltaMVTT was 2.6 seconds (sensitivity 46.4% and specificity 85.7% as a
predictor of postoperative HPS). A DeltaMVTT > 2.6 seconds was an independent
predictor of HPS in multivariate analysis (hazard ratio 4.88, 95% CI 1.76-13.57;
p = 0.002). CONCLUSIONS MVTT in patients with MMD was reduced significantly after
bypass surgery. Patients with a DeltaMVTT > 2.6 seconds tended to develop
postoperative HPS. Because DeltaMVTT can be easily measured during surgery, it is
a useful diagnostic tool for identifying patients at high risk for HPS after STA
MCA bypass surgery for MMD.
PMID- 28498061
TI - Microvascular decompression for hemifacial spasm: can intraoperative lateral
spread response monitoring improve surgical efficacy?
AB - OBJECTIVE The purpose of this study was to evaluate whether intraoperative
monitoring of lateral spread response (LSR) improves the efficacy of
microvascular decompression (MVD) for hemifacial spasm (HFS). METHODS In this
prospective study, patients undergoing MVD for HFS were assigned to one of 2
groups, Group A (MVD with intraoperative LSR monitoring) or Group B (MVD without
LSR monitoring). Clinical outcome at 12 months after surgery was assessed through
telephone survey. Data analysis was performed to investigate the effect of
intraoperative LSR monitoring on efficacy of MVD. RESULTS A total of 283 patients
were enrolled in the study, 145 in Group A and 138 in Group B. There was no
statistically significant difference between the 2 groups with respect to the
percentage of patients who had spasm relief at either 1 week (Group A 87.59% vs
Group B 83.33%; p = 0.317) or 1 year (93.1% vs 94.2%; p = 0.809) after surgery. A
clear-cut elimination of LSR during surgery was observed in 131 (90.34%) of 145
patients; LSR persisted in 14 patients (9.66%) at the end of the surgical
procedure. Disappearance of LSR correlated with spasm-free status at 1 week
postoperatively (p = 0.017) but not at 1 year postoperatively (p = 0.249).
CONCLUSIONS Intraoperative LSR monitoring does not appear to provide significant
benefit with respect to the outcome of MVD for HFS in skilled hands. Persistence
of LSR does not always correlate with poor outcome, and LSR elimination should
not be pursued in all patients after verification of complete decompression.
PMID- 28498062
TI - Telemedicine is helping the parents of children with neurodevelopmental disorders
living in remote and deprived areas.
AB - Telecommunication technologies are advancing rapidly with huge investment to
improve infrastructure in rural areas. Telemedicine brings the benefits of
telecommunication to healthcare, especially in resource-limited and remote
communities. The recent literature on telemedicine in paediatrics will be
reviewed, with particular focus on its application to help children with
neurodevelopmental disorders and their families living in remote regions and/or
low-income countries, and gaps identified for future research. Studies show that
telemedicine can enable a family's access to appropriately qualified help that
physically may only be available hundreds of miles away, helping to overcome
geographic barriers. Telemedicine can also train parents and equip them with the
knowledge and skills to better care for their children. Despite some
technological barriers to implementation, telemedicine can help transform all
stages of autism treatment. However, more studies are required in low- and middle
income countries to fully elucidate the benefits offered by telemedicine to
autistic children and their families.
PMID- 28498063
TI - Preliminary Evaluation of a Novel Rigid Bronchoscopy Simulator.
AB - PURPOSE: Emergent retrieval of airway foreign bodies (AFBs) in children remains a
priority skill set for pediatric surgeons. In the setting of low procedural
volume, simulation-based education with deliberate practice is essential to
ensure trainees reach expected surgical competency. The purposes of this work
were to (1) create a realistic rigid bronchoscopy for AFB retrieval simulation
model and (2) to evaluate preliminary validity evidence of a novel simulator for
the use of training and assessing pediatric surgical trainees' rigid bronchoscopy
skills. METHODS: After institutional review board exemption determination, 18
participants performed AFB retrieval of two different objects on a novel
simulator that represented an 18-month-old pediatric tracheobronchial airway.
Participants reported their experience and comfort level, and rated the simulator
across two domains-Authenticity and their Ability to perform tasks. Authenticity
was measured by 23 items across five subdomains (Visual Attributes, Materials'
Response, Realism of Experience, Value and Relevance, and Global Value).
Participants who had previously performed >=10 rigid bronchoscopies were
categorized as "experienced," while those reporting <10 were considered "novice."
Validity evidence relevant to test content and internal structure was evaluated
using a many-facet Rasch model. RESULTS: Novice surgeons (n = 12) had previously
performed a mean of 2.7 (+/-2.0) rigid bronchoscopies, compared to 15.4 (+/-7.7)
by experienced surgeons (n = 6). For both models, the Value and Relevance
subdomain received the highest ratings (observed average [OA] = 3.9, while
Materials' Response received the lowest (OA <3.0). Participants' Global Value
rating for this model was consistent with "requires minor improvements before it
can be considered for use in rigid bronchoscopy training." CONCLUSIONS: We
successfully designed, assembled, and evaluated a novel pediatric rigid
bronchoscopy model for AFB retrieval. The model was considered as relevant to
educational needs and valuable as a testing and training tool. With recommended
improvements, the model could be used for implementation with a Mastery Learning
curriculum.
PMID- 28498064
TI - Polydopamine/polyethyleneimine complex adhered to micrometer-sized magnetic
carbon fibers for high-efficiency hemoperfusion.
AB - Carbon-based nanomaterials have recently attracted tremendous attention in
adsorption, separation and biological fields. However, such modification is not
always straightforward when the surface is not chemically reactive. Given this
reason, most carbon materials modification processes employ reactive linkers or
coupling agents, which are complicated and time-consuming. Herein, we report on a
dopamine-polyethyleneimine (PEI) coating strategy to fabricate micrometer-sized
magnetic carbon fiber (MSMCF)-based extracorporeal blood-cleansing sorbent for
hemoperfusion. Results showed that the dopamine/PEI-coated MSMCF had a twisted
fiber shape with a size range of 80-120 MUm in diameter and porous structure with
a specific surface area of 146 m2 g-1. Adsorption behavior of dopamine/PEI
modified MSMCF was examined by using bilirubin as a toxin model compound.
Equilibrium data were well fitted to the Langmuir isotherm model with a maximal
adsorption capacity of 335.1 mg g-1 at ambient temperature. The as-obtained
material had relatively high bilirubin adsorption selectivity against albumin at
a normal albumin concentration. In particular, the dopamine/PEI-coated MSMCF has
excellent adsorption capacity and hemocompatibility compared to the MSMCF
decorated only by dopamine or PEI. Therefore, this work may pave the way for
enhancing the property of the extracorporeal blood-cleansing sorbent during
hemoperfusion.
PMID- 28498065
TI - Effect of Interval and Continuous Aerobic Training on Basal Serum and Plasma
Brain-Derived Neurotrophic Factor Values in Seniors: A Systematic Review of
Intervention Studies.
AB - The purpose of this systematic review was to provide a comprehensive analysis of
the available clinical trials analyzing, in seniors, the effect of interval
aerobic training (IAT) and continuous aerobic training (CAT) on peripheral brain
derived neurotrophic factor (BDNF) concentration. We identified 14 randomized or
not-randomized intervention studies published up to January 2017 through a
computer-assisted search (PUBMED, Pedro, and Science direct data bases). The five
trials considering IAT and the nine considering CAT totalized 988 individuals
(age range: 58.1-77 years). The parameters of aerobic training (AT) protocol in
terms of frequency and intensity are the primary determinants of the BDNF
response to AT. The interpretation of the relationship between AT and BDNF
signaling pathway was very challenging when specific health conditions were taken
into consideration. This was more particularly true with mild cognitive
impairment or depressive symptoms. These findings argue in favor of a
generalization of the practice of AT and show that the type of training is not
the main determining factor of the increase in BDNF level, which results more
from the combination of several factors such as intensity and frequency of
sessions, duration of programs, and also some genetic determinant coding for BDNF
protein. All these factors have to be carefully addressed in future researches in
that field. Thus, further researches are still necessary to better the signaling
pathway by which AT contributes to better health outcomes.
PMID- 28498066
TI - Atrial fibrillation in pregnancy: a growing challenge.
AB - BACKGROUND: Atrial fibrillation (AF) constitutes a relatively infrequent
pregnancy complication, which may be a therapeutic Gordian knot. Indeed, sparse
data exist regarding the prevalence, prognosis, and management of AF during
pregnancy. In general, AF occurs as a benign, self-limited arrhythmia, but
occasionally may have severe hemodynamic consequences in pregnant patients
suffering from heart failure, congenital heart disease, or other comorbidities.
Extra-cardiac causes of AF should always be meticulously excluded. REVIEW:
Treatment decisions are difficult, since medications may cross the placental
barrier and potentially affect fetal growth and organogenesis, or even result in
fetal bradyarrhythmias. Treatment goals are not differentiated in comparison to
those regarding AF occurring in the general population. Still, while maternal
treatment is prioritized, issues regarding fetal health must deliberately be
considered. Consequently, hemodynamic instability is to be promptly treated with
synchronized electrical cardioversion. In contrast, in stable patients,
pharmacologic cardioversion, under appropriate antithrombotic regimen, should be
attempted. Selection of appropriate antithrombotic therapy, including novel oral
anticoagulants, imposes further difficulties on therapeutic decision-making.
Further clinical trials are warranted in order to assess the pathophysiology and
prognosis of AF in pregnancy and ameliorate the evidence-based therapeutic
strategy in this specific group of the population.
PMID- 28498067
TI - Characterization and migration of oil and solids in oily sludge during
centrifugation.
AB - The migration behaviors of oil, water and solids in sludge during centrifugation
were elaborated. Size distribution, surface topography and lypohydrophilic
properties were studied in detail. The average size of solids was 61 MUm in
original sludge, 31 MUm in upper layer and 235 MUm in bottom layer. The result
shows that solvent is essential to separate oil phase into molecular light and
weight fractions during centrifugation. With solvent/oil ratio increases from
1:2, 1:1, 2:1 to 5:1, molecular weight in upper layer decreases from 1044, 1043,
1020 to 846 combined with that in bottom layer increases. A model was proposed to
calculate the oil residue content in solid phases after sedimentation. The
findings of this paper provide information for optimizing the oil recovery and
clean treatment.
PMID- 28498068
TI - Predictors of extended length of stay, discharge to inpatient rehab, and hospital
readmission following elective lumbar spine surgery: introduction of the Carolina
Semmes Grading Scale.
AB - OBJECTIVE Extended hospital length of stay (LOS), unplanned hospital readmission,
and need for inpatient rehabilitation after elective spine surgery contribute
significantly to the variation in surgical health care costs. As novel payment
models shift the risk of cost overruns from payers to providers, understanding
patient-level risk of LOS, readmission, and inpatient rehabilitation is critical.
The authors set out to develop a grading scale that effectively stratifies risk
of these costly events after elective surgery for degenerative lumbar
pathologies. METHODS The Quality and Outcomes Database (QOD) registry
prospectively enrolls patients undergoing surgery for degenerative lumbar spine
disease. This registry was queried for patients who had undergone elective 1- to
3-level lumbar surgery for degenerative spine pathology. The association between
preoperative patient variables and extended postoperative hospital LOS (LOS >= 7
days), discharge status (inpatient facility vs home), and 90-day hospital
readmission was assessed using stepwise multivariate logistic regression. The
Carolina-Semmes grading scale was constructed using the independent predictors
for LOS (0-12 points), discharge to inpatient facility (0-18 points), and 90-day
readmission (0-6 points), and its performance was assessed using the QOD data
set. The performance of the grading scale was then confirmed separately after
using it in 2 separate neurosurgery practice sites (Carolina Neurosurgery & Spine
Associates [CNSA] and Semmes Murphey Clinic). RESULTS A total of 6921 patients
were analyzed. Overall, 290 (4.2%) patients required extended LOS, 654 (9.4%)
required inpatient facility care/rehabilitation on hospital discharge, and 474
(6.8%) were readmitted to the hospital within 90 days postdischarge. Variables
that remained as independently associated with these unplanned events in
multivariate analysis included age >= 70 years, American Society of
Anesthesiologists Physical Classification System class > III, Oswestry Disability
Index score >= 70, diabetes, Medicare/Medicaid, nonindependent ambulation, and
fusion. Increasing point totals in the Carolina-Semmes scale effectively
stratified the incidence of extended LOS, discharge to facility, and readmission
in a stepwise fashion in both the aggregate QOD data set and when subsequently
applied to the CNSA/Semmes Murphey practice groups. CONCLUSIONS The authors
introduce the Carolina-Semmes grading scale that effectively stratifies the risk
of prolonged hospital stay, need for postdischarge inpatient facility care, and
90-day hospital readmission for patients undergoing first-time elective 1- to 3
level degenerative lumbar spine surgery. This grading scale may be helpful in
identifying patients who may require additional resource utilization within a
global period after surgery.
PMID- 28498069
TI - An analysis from the Quality Outcomes Database, Part 2. Predictive model for
return to work after elective surgery for lumbar degenerative disease.
AB - OBJECTIVE Current costs associated with spine care are unsustainable.
Productivity loss and time away from work for patients who were once gainfully
employed contributes greatly to the financial burden experienced by individuals
and, more broadly, society. Therefore, it is vital to identify the factors
associated with return to work (RTW) after lumbar spine surgery. In this
analysis, the authors used data from a national prospective outcomes registry to
create a predictive model of patients' ability to RTW after undergoing lumbar
spine surgery for degenerative spine disease. METHODS Data from 4694 patients who
underwent elective spine surgery for degenerative lumbar disease, who had been
employed preoperatively, and who had completed a 3-month follow-up evaluation,
were entered into a prospective, multicenter registry. Patient-reported outcomes
Oswestry Disability Index (ODI), numeric rating scale (NRS) for back pain (BP)
and leg pain (LP), and EQ-5D scores-were recorded at baseline and at 3 months
postoperatively. The time to RTW was defined as the period between operation and
date of returning to work. A multivariable Cox proportional hazards regression
model, including an array of preoperative factors, was fitted for RTW. The model
performance was measured using the concordance index (c-index). RESULTS Eighty
two percent of patients (n = 3855) returned to work within 3 months
postoperatively. The risk-adjusted predictors of a lower likelihood of RTW were
being preoperatively employed but not working at the time of presentation, manual
labor as an occupation, worker's compensation, liability insurance for
disability, higher preoperative ODI score, higher preoperative NRS-BP score, and
demographic factors such as female sex, African American race, history of
diabetes, and higher American Society of Anesthesiologists score. The likelihood
of a RTW within 3 months was higher in patients with higher education level than
in those with less than high school-level education. The c-index of the model's
performance was 0.71. CONCLUSIONS This study presents a novel predictive model
for the probability of returning to work after lumbar spine surgery. Spine care
providers can use this model to educate patients and encourage them in shared
decision-making regarding the RTW outcome. This evidence-based decision support
will result in better communication between patients and clinicians and improve
postoperative recovery expectations, which will ultimately increase the
likelihood of a positive RTW trajectory.
PMID- 28498070
TI - Extracranial internal carotid artery dissection caused by compression from a
giant osteophyte due to atlantoaxial osteoarthritis: case report.
AB - Deformed osseous structures have been reported as rare causes of extracranial
internal carotid artery (ICA) dissection, including the styloid process and the
hyoid bone. Here, the authors describe the first known case of symptomatic ICA
dissection caused by a giant osteophyte due to atlantoaxial osteoarthritis. The
left ICA was fixed at the skull base and at the ICA portion compressed by the
osteophyte, and it was highly stretched and injured between the two portions
during neck rotation. The patient was successfully treated with ligation of the
affected ICA following balloon test occlusion. Atlantoaxial osteoarthritis should
be considered in the differential diagnosis of ICA dissection in patients with a
severely deformed cervical spine.
PMID- 28498071
TI - Assessment of malpractice claims due to spinal epidural abscess.
AB - OBJECTIVE Spinal epidural abscesses (SEAs) can be difficult to diagnose and may
result in neurological compromise or even death. Delays in diagnosis or treatment
may worsen the prognosis. While SEA presents a high risk for litigation, little
is known about the medicolegal ramifications of this condition. An enhanced
understanding of potential legal implications is important for practicing spine
surgeons, emergency medicine physicians, and internists. METHODS The
VerdictSearch database, a large legal-claims database, was queried for "epidural
abscess"-related legal cases. Demographic and clinical data were examined for all
claims; any irrelevant cases or cases with incomplete information were excluded.
The effects of age of the plaintiff, sex of the plaintiff, presence of a known
infection, resulting paraplegia or quadriplegia, delay in diagnosis, and delay in
treatment on the proportion of plaintiff rulings and size of payments were
assessed. RESULTS In total, 56 cases met the inclusion criteria. Of the 56 cases,
17 (30.4%) were settled, 22 (39.3%) resulted in a defendant ruling, and 17
(30.4%) resulted in a plaintiff ruling. The mean award for plaintiff rulings was
$5,277,468 +/- $6,348,462 (range $185,000-$19,792,000), which was significantly
larger than the mean award for cases that were settled out of court, $1,914,265
+/- $1,313,322 (range $100,000-$4,500,000) (p < 0.05). The mean age of the
plaintiffs was 47.0 +/- 14.4 years; 23 (41.1%) of the plaintiffs were female and
33 (58.9%) were male. The proportion of plaintiff verdicts and size of monetary
awards were not affected by age or sex (p > 0.49). The presence of a previously
known infection was also not associated with the proportion of plaintiff verdicts
or indemnity payments (p > 0.29). In contrast, juries were more likely to rule in
favor of plaintiffs who became paraplegic or quadriplegic (p = 0.03) compared
with plaintiffs who suffered pain or isolated weakness. Monetary awards for
paraplegic or quadriplegic patients were also significantly higher (p = 0.003).
Plaintiffs were more likely to win if there was a delay in diagnosis (p = 0.04)
or delay in treatment (p = 0.006), although there was no difference in monetary
awards (p > 0.57). Internists were the most commonly sued physician (named in 13
suits [23.2%]), followed by emergency medicine physicians (named in 8 [14.3%]),
and orthopedic surgeons (named in 3 [5.4%]). CONCLUSIONS This investigation is
the largest examination of legal claims due to spinal epidural abscess to date.
The proportion of plaintiff verdicts was significantly higher in cases in which
the patient became paraplegic or quadriplegic and in cases in which there was
delay in diagnosis or treatment. Additionally, paralysis is linked to large sums
awarded to the plaintiff. Nonsurgeon physicians, who are often responsible for
initial diagnosis, were more likely to be sued than were surgeons.
PMID- 28498072
TI - Paravertebral foramen screw fixation for posterior cervical spine fusion:
biomechanical study and description of a novel technique.
AB - OBJECTIVE Fusion surgery with instrumentation is a widely accepted treatment for
cervical spine pathologies. The authors propose a novel technique for subaxial
cervical fusion surgery using paravertebral foramen screws (PVFS). The authors
consider that PVFS have equal or greater biomechanical strength than lateral mass
screws (LMS). The authors' goals of this study were to conduct a biomechanical
study of PVFS, to investigate the suitability of PVFS as salvage fixation for
failed LMS, and to describe this novel technique. METHODS The authors harvested
24 human cervical spine vertebrae (C3-6) from 6 fresh-frozen cadaver specimens
from donors whose mean age was 84.3 +/- 10.4 years at death. For each vertebra,
one side was chosen randomly for PVFS and the other for LMS. For PVFS, a 3.2-mm
drill with a stopper was advanced under lateral fluoroscopic imaging. The drill
stopper was set to 12 mm, which was considered sufficiently short not to breach
the transverse foramen. The drill was directed from 20 degrees to 25 degrees
medially so that the screw could purchase the relatively hard cancellous bone
around the entry zone of the pedicle. The hole was tapped and a 4.5-mm-diameter *
12-mm screw was inserted. For LMS, 3.5-mm-diameter * 14-mm screws were inserted
into the lateral mass of C3-6. The pullout strength of each screw was measured.
After pullout testing of LMS, a drill was inserted into the screw hole and the
superior cortex of the lateral mass was pried to cause a fracture through the
screw hole, simulating intraoperative fracture of the lateral mass. After the
procedure, PVFS for salvage (sPVFS) were inserted on the same side and pullout
strength was measured. RESULTS The CT scans obtained after screw insertion
revealed no sign of pedicle breaching, violation of the transverse foramen, or
fracture of the lateral mass. A total of 69 screws were tested (23 PVFS, 23 LMS,
and 23 sPVFS). One vertebra was not used because of a fracture that occurred
while the specimen was prepared. The mean bone mineral density of the specimens
was 0.29 +/- 0.10 g/cm3. The mean pullout strength was 234 +/- 114 N for PVFS,
158 +/- 91 N for LMS, and 195 +/- 125 N for sPVFS. The pullout strength for PVFS
tended to be greater than that for LMS. However, the difference was not quite
significant (p = 0.06). CONCLUSIONS The authors introduce a novel fixation
technique for the subaxial cervical spine. This study suggests that PVFS tend to
provide stronger fixation than LMS for initial applications and fixation equal to
LMS for salvage applications. If placement of LMS fails, PVFS can serve as a
salvage fixation technique.
PMID- 28498073
TI - Does the mesodermal derangement in Chiari Type I malformation extend to the
cervical spine? Evidence from an analytical morphometric study on cervical
paraspinal muscles.
AB - OBJECTIVE The mesodermal derangement in Chiari Type I malformation (CMI) has been
postulated to encompass the cervical spine. The objectives of this study were to
assess the cross-sectional areas (CSAs) of cervical paraspinal muscles (PSMs) in
patients with CMI without syringomyelia, compare them with those in non-CMI
subjects, and evaluate their correlations with various factors. METHODS In this
retrospective study, the CSAs of cervical PSMs in 25 patients were calculated on
T2-weighted axial MR images and computed as ratios with respect to the
corresponding vertebral body areas. These values and the cervical taper ratios
were then compared with those of age- and sex-matched non-CMI subjects and
analyzed with respect to demographic data and clinicoradiological factors.
RESULTS Compared with the non-CMI group, the mean CSA values for the rectus
capitis minor and all of the subaxial PSMs were lower in the study group, and
those of the deep extensors were significantly lower (p = 0.004). The cervical
taper ratio was found to be significantly higher in the study cohort (p =
0.0003). A longer duration of symptoms and a steeper cervical taper ratio were
independently associated with lower CSA values for the deep extensors (p = 0.04
and p = 0.03, respectively). The presence of neck pain was associated with a
lower CSA value for the deep flexors (p = 0.03). CONCLUSIONS Patients with CMI
demonstrate alterations in their cervical paraspinal musculature even in the
absence of coexistent syringomyelia. Their deep extensor muscles undergo
significant atrophic changes that worsen with the duration of their symptoms.
This could be related to a significantly steeper cervical taper ratio that their
cervical cords are exposed to. Neck pain in these patients is related to atrophy
of their deep flexor muscles. A steeper cervical taper ratio and alterations in
the PSMs could be additional indicators for surgery in patients with CMI without
syringomyelia.
PMID- 28498074
TI - An analysis from the Quality Outcomes Database, Part 1. Disability, quality of
life, and pain outcomes following lumbar spine surgery: predicting likely
individual patient outcomes for shared decision-making.
AB - OBJECTIVE Quality and outcomes registry platforms lie at the center of many
emerging evidence-driven reform models. Specifically, clinical registry data are
progressively informing health care decision-making. In this analysis, the
authors used data from a national prospective outcomes registry (the Quality
Outcomes Database) to develop a predictive model for 12-month postoperative pain,
disability, and quality of life (QOL) in patients undergoing elective lumbar
spine surgery. METHODS Included in this analysis were 7618 patients who had
completed 12 months of follow-up. The authors prospectively assessed baseline and
12-month patient-reported outcomes (PROs) via telephone interviews. The PROs
assessed were those ascertained using the Oswestry Disability Index (ODI), EQ-5D,
and numeric rating scale (NRS) for back pain (BP) and leg pain (LP). Variables
analyzed for the predictive model included age, gender, body mass index, race,
education level, history of prior surgery, smoking status, comorbid conditions,
American Society of Anesthesiologists (ASA) score, symptom duration, indication
for surgery, number of levels surgically treated, history of fusion surgery,
surgical approach, receipt of workers' compensation, liability insurance,
insurance status, and ambulatory ability. To create a predictive model, each 12
month PRO was treated as an ordinal dependent variable and a separate
proportional-odds ordinal logistic regression model was fitted for each PRO.
RESULTS There was a significant improvement in all PROs (p < 0.0001) at 12 months
following lumbar spine surgery. The most important predictors of overall
disability, QOL, and pain outcomes following lumbar spine surgery were employment
status, baseline NRS-BP scores, psychological distress, baseline ODI scores,
level of education, workers' compensation status, symptom duration, race,
baseline NRS-LP scores, ASA score, age, predominant symptom, smoking status, and
insurance status. The prediction discrimination of the 4 separate novel
predictive models was good, with a c-index of 0.69 for ODI, 0.69 for EQ-5D, 0.67
for NRS-BP, and 0.64 for NRS-LP (i.e., good concordance between predicted
outcomes and observed outcomes). CONCLUSIONS This study found that preoperative
patient-specific factors derived from a prospective national outcomes registry
significantly influence PRO measures of treatment effectiveness at 12 months
after lumbar surgery. Novel predictive models constructed with these data hold
the potential to improve surgical effectiveness and the overall value of spine
surgery by optimizing patient selection and identifying important modifiable
factors before a surgery even takes place. Furthermore, these models can advance
patient-focused care when used as shared decision-making tools during
preoperative patient counseling.
PMID- 28498075
TI - The impact of 6-thioguanine incorporation into DNA on the function of DNA
methyltransferase Dnmt3a.
AB - The incorporation of chemotherapeutic agent 6-thioguanine (SG) into DNA is a
prerequisite for its cytotoxic action. This modification of DNA impedes the
activity of enzymes involved in DNA repair and replication. Here, using
hemimethylated DNA substrates we demonstrated that DNA methylation by Dnmt3a-CD
is reduced if DNA is damaged by the incorporation of SG into one or two CpG sites
separated by nine base pairs. An increase in the number of SG substitutions did
not enhance the effect. Dnmt3a-CD binding to either of SG-containing DNA
substrates was not distorted. Our results suggest that SG incorporation into DNA
may influence epigenetic regulation via DNA methylation.
PMID- 28498076
TI - Cochlear implantation in Mondini's deformity: could the straight electrode array
with length of 31 mm be fully inserted?
AB - CONCLUSIONS: The straight electrode array with length of 31 mm can be fully
inserted using round window insertion in cochlear implantation with Mondini's
deformity. It is a safe and effective process, but also a challenging task of the
full implantation in children with Mondini's deformity. OBJECTIVE: The aim of
this study is to discuss whether the straight electrode array with a length of 31
mm could be fully inserted in cochlear implantation with Mondini's deformity.
METHODS: A chart review of 30 patients undergoing cochlear implantation with
Mondini's deformity using the electrode array with length of 31 mm was undertaken
from January 2012 and December 2015 in Anhui Provincial Hospital. RESULTS: Full
insertion of the straight electrode array with length of 31 mm were performed
successfully in all patients with Mondini's deformity using round window
insertion. Resistance was not encountered while introducing the electrodes. Ten
of 30 patients had cerebrospinal fluid drainage during cochlear implantation.
Cerebrospinal fluid drainage was controlled with small pieces of temporalis
fascia packing round window in all patients. Intra-operative neural response
telemetry was performed in all patients, and results were good. The result of X
ray showed proper placement of the cochlear implant electrode array. During
surgery, no patients had experienced any immediate or delayed post-operative
complications such as wound infection, intracranial complication, extrusion, or
migration of the implant during an average follow-up period of 6-36 months.
PMID- 28498077
TI - The effect of platelet-rich fibrin membrane on the repair of perforated tympanic
membrane: an experimental study.
AB - CONCLUSION: Platelet-rich fibrin (PRF) membrane could be used successfully in the
repair of tympanic membrane perforation and wound healing. OBJECTIVES: To
evaluate the effect of platelet-rich fibrin membrane in the repair of perforated
tympanic membrane. METHODS: After otoscopic examination, a 3-mm perforation was
made in the posterior quadrant of both tympanic membranes of 50 adult male
Sprague-Dawley rats. Venous blood was withdrawn from the rats, then centrifuged.
PRF was obtained in membrane form. The membrane was placed on the right tympanic
membrane perforation. The perforations on the left side were left to
spontaneously heal and, thus, formed the control group. Daily examinations were
made of 20 rats and the time to healing of the tympanic membrane was recorded.
The remaining 30 rats were separated into five groups of six, and
histopathological examination was made. Evaluation was made in respect of the
presence of oedema in the lamina propria, neovascularization, fibroblastic
reaction, and inflammatory cells. RESULTS: The healing time of the tympanic
membrane perforation was determined as mean 10.3 +/- 2.18 days in the study group
applied with PRF and 17 +/- 2.40 days in the control group. Higher values in
respect of fibrosis and neovascularization were obtained in the study group.
PMID- 28498078
TI - Kinetic oscillatory stimulation of nasal mucosa in non-allergic rhinitis:
comparison of patient self-administration and caregiver administration regarding
pain and treatment effect. A randomized clinical trial.
AB - CONCLUSION: Patient self-administration of the Kinetic Oscillatory Stimulation
(KOS)-catheter was a fully acceptable alternative to insertion of the catheter by
physician with helmet fixation, in patients with non-allergic rhinitis (NAR). The
approaches were equivalent regarding pain. The treatment effect in the patient
self-administration group was not inferior. OBJECTIVES: To evaluate whether self
administration of a KOS-catheter was different compared to insertion by a
physician, assessed with patient reported pain on a visual analogue scale (VAS).
Also, to evaluate the difference in nasal stuffiness with the Sino-Nasal Outcome
Test (SNOT-22) and Peak Nasal Inspiratory Flow (PNIF). METHODS: Patients with NAR
were randomized to group 1, patient insertion of catheter and manual fixation,
and group 2, catheter insertion by physician and fixation with a helmet. Patients
were treated once, 10 min in each nasal cavity, and followed up 14 days later.
RESULTS: Twenty-nine patients were included (group 1, n = 14; group 2, n = 15).
There was no statistical significant difference in patient reported pain between
groups. There was a decrease in nasal stuffiness after treatment in the total
study population (n = 26, p = 0.001). In group 1 nasal stuffiness was decreased
and in group 2 there was no change (group 1, p = 0.004; group 2, p = 0.071). No
statistical significant change in PNIF was observed.
PMID- 28498079
TI - Outcomes of cochlear implantation for the patients with specific genetic
etiologies: a systematic literature review.
AB - CONCLUSION: Most of the cases with gene mutations of intra-cochlear etiology
showed relatively good CI outcomes. To progress toward more solid evidence-based
CI intervention, a greater number of reports including CI outcomes for specific
gene mutations are desired. BACKGROUND: Cochlear implantation (CI) is the most
important and effective treatment for patients with profound sensorineural
hearing loss. However, the outcomes of CI vary among patients. One of the reasons
of this heterogeneous outcome for cochlear implantation is thought to be the
heterogeneous nature of hearing loss. Indeed, genetic factors, the most common
etiology in severe-to-profound hearing loss, might be one of the key determinants
of outcomes for CI and electric acoustic stimulation (EAS). Patients with genetic
causes involving an 'intra-cochlear' etiology show good CI/EAS outcomes. REVIEW:
This review article aimed to summarize the reports on CI/EAS outcomes in patients
with special genetic causes as well as to assist in future clinical decision
making. Most of the cases were suspected of an intra-cochlear etiology, such as
those with GJB2, SLC26A4, and OTOF mutations, which showed relatively good CI
outcomes. However, there have only been a limited number of reports on patients
with other gene mutations.
PMID- 28498080
TI - HB-EGF expression as a potential biomarker of acquired middle ear cholesteatoma.
AB - CONCLUSIONS: The heparin-binding epidermal growth factor-like growth factor (HB
EGF) plays an essential role in the development and invasiveness of
cholesteatoma. This study may help to realize the molecular mechanisms underlying
the pathogenesis of cholesteatoma and make HB-EGF a promising target for drug
intervention of cholesteatoma. OBJECTIVE: To detect HB-EGF expression in human
surgical specimens of acquired middle ear cholesteatoma and analyze its
functional role as a regulator of epithelial keratinocytes hyperproliferation.
METHODS: A total of 34 patients who underwent surgical treatment for middle ear
cholesteatoma were recruited in the study. The mRNA and protein expression of HB
EGF in middle ear cholesteatoma tissues and normal postauricular skin tissues was
investigated by real-time quantitative reverse-transcription-polymerase chain
reaction (RT-qPCR), immunohistochemical staining, and western blot. The
correlation between bone resorption degree and HB-EGF expression was also
analyzed. RESULTS: On average, compared with normal postauricular skin,
expression of HB-EGF mRNA in the cholesteatoma epithelium was significantly
elevated 2.41-fold by RT-qPCR, and HB-EGF protein significantly upregulated 2.32
fold by western blot. Positive HB-EGF immunostaining observed in the basal and
suprabasal layers of cholesteatoma epithelium was significantly stronger than in
normal postauricular skin. Meanwhile, an obviously positive correlation between
HB-EGF protein expression and bone resorption degree was discovered.
PMID- 28498081
TI - Finite element analysis of auditory characteristics in patients with middle ear
diseases.
AB - CONCLUSION: This study validates that a finite element model of the human
ossicular chain and tympanic membrane can be used as an effective surgical
assessment tool in clinics. OBJECTIVE: The present study was performed to
investigate the application of a finite element model of ossicular chain and
tympanic membrane for fabrication of individualized artificial ossicles. METHODS:
Twenty patients (20 ears) who underwent surgery for middle ear disease (n = 20)
and 10 healthy controls (10 ears) were enrolled in the hospital. Computed
tomography (CT) and pure tone audiometry were performed before and after surgery.
A finite element model was developed using CT scans, and correlation analysis was
conducted between stapes displacement and surgical methods. An audiometric test
was also performed for 14 patients before and after surgery. RESULTS: Stapes
displacement in the healthy group (average = 3.31 * 10-5 mm) was significantly
greater than that in the impaired group (average = 1.41 * 10-6 mm) prior to
surgery. After surgery, the average displacement in the impaired group was 2.55 *
10-6 mm, which represented a significant improvement. For the patients who
underwent the audiometric test, 10 improved hearing after surgery, and stapes
displacement increased in nine of these 10 patients.
PMID- 28498082
TI - The Safety and Feasibility of Re-treating Patients with Severe Emphysema with
Endobronchial Coils: A Pilot Study.
AB - Severe emphysema patients who have been treated with endobronchial coils have
been shown to initially benefit, but slowly decline in the years thereafter. Re
treating a patient with endobronchial coils could potentially lead to new
improvements and may again reduce the rate of further decline. To our knowledge,
until now, no results are published about patients who are re-treated. The
primary aim of this study is to investigate the safety and feasibility of re
treating severe emphysema patients with endobronchial coils, using the PneumRx
coil system. Furthermore, as secondary aim, we will evaluate the efficacy of re
treating these patients. Patients who at least 2 years ago were treated with
endobronchial coils and responded clinically meaningful to this treatment were
included in the study and re-treated. Safety was evaluated by the number of
reported adverse events. Efficacy was evaluated 6 months after re-treatment, and
measured by the change in quality of life, exercise capacity and pulmonary
function testing. Eight patients were re-treated at a median of 1382 days (range
849-1545) after initial coil treatment with a median additional of 12 (10-15)
coils per patient. During treatment, and until 6 months of follow-up, no
unexpected adverse events occurred. Quality of life, exercise capacity and lung
function did not change significantly 6 months after re-treatment. The results of
this pilot study suggest that re-treating patients with endobronchial coils is
feasible and safe. However, larger studies are needed to confirm these results
and to investigate the efficacy and thus the clinical relevance.
PMID- 28498083
TI - Computer-assisted CI fitting: Is the learning capacity of the intelligent agent
FOX beneficial for speech understanding?
AB - OBJECTIVE: The software application FOX ('Fitting to Outcome eXpert') is an
intelligent agent to assist in the programing of cochlear implant (CI)
processors. The current version utilizes a mixture of deterministic and
probabilistic logic which is able to improve over time through a learning effect.
This study aimed at assessing whether this learning capacity yields measurable
improvements in speech understanding. METHODS: A retrospective study was
performed on 25 consecutive CI recipients with a median CI use experience of 10
years who came for their annual CI follow-up fitting session. All subjects were
assessed by means of speech audiometry with open set monosyllables at 40, 55, 70,
and 85 dB SPL in quiet with their home MAP. Other psychoacoustic tests were
executed depending on the audiologist's clinical judgment. The home MAP and the
corresponding test results were entered into FOX. If FOX suggested to make MAP
changes, they were implemented and another speech audiometry was performed with
the new MAP. RESULTS: FOX suggested MAP changes in 21 subjects (84%). The within
subject comparison showed a significant median improvement of 10, 3, 1, and 7% at
40, 55, 70, and 85 dB SPL, respectively. All but two subjects showed an
instantaneous improvement in their mean speech audiometric score. DISCUSSION:
Persons with long-term CI use, who received a FOX-assisted CI fitting at least 6
months ago, display improved speech understanding after MAP modifications, as
recommended by the current version of FOX. This can be explained only by
intrinsic improvements in FOX's algorithms, as they have resulted from learning.
This learning is an inherent feature of artificial intelligence and it may yield
measurable benefit in speech understanding even in long-term CI recipients.
PMID- 28498087
TI - An expert opinion on PANDAS/PANS: highlights and controversies.
AB - OBJECTIVES: 'Pediatric Autoimmune Neuropsychiatric Disorders Associated with
Streptococcal Infections' (PANDAS) identified a unique subgroup of patients with
abrupt onset of obsessive compulsive disorder (OCD) symptoms clinically related
to Streptococcus infection and accompanied by neuropsychological and motor
symptoms. After almost 20 years, PANDAS has not been accepted as distinct
disorder and new criteria for paediatric acute-onset neuropsychiatric syndrome
(PANS) have been replaced it, highlighting the fact that several agents rather
than only Streptococcus might be involved. METHODS: Extensive review of the
PANDAS/PANS literature was performed on PubMed. RESULTS: Although antibiotics
have been reported to be effective for acute and prophylactic phases in several
uncontrolled studies and non-steroidal anti-inflammatory drugs (NSAID) are used
during exacerbations, clinical multicenter trials are still missing. Selective
serotonin reuptake inhibitors (SSRIs) and cognitive behavioural therapy (CBT) are
still the first line of recommendation for acute onset OCD spectrum.
Immunological therapies should be restricted to a few cases. CONCLUSIONS: While
PANDAS has found no confirmation as a distinct syndrome, and it is not presented
in DSM-5, patients with acute onset OCD spectrum, neurocognitive and motor
symptoms should be evaluated for inflammatory, infective, immunological and
metabolic abnormalities with a comprehensive diagnostic algorithm.
PMID- 28498088
TI - Mental health problems of second generation children and adolescents with
migration background.
AB - OBJECTIVE: Despite the growing number of young second-generation immigrant (SGI)
children and adolescents, studies about their mental health are rare. The
objective of this study was to investigate the mental health problems of SGI
children and adolescents in Istanbul, Turkey. METHODS: In a clinical sample the
mental health of 54 SGIs and 50 native children and adolescents were examined
using the Schedule for Affective Disorders and Schizophrenia for School Aged
Children-Present and Lifetime Version (K-SADS-PL) and Children's Global
Assessment Scale. The assessments were carried out by a blinded rater. RESULTS:
SGI children had higher rates of psychiatric disorders such as depression (p =
0.001), post-traumatic stress disorder (PTSD) (p = 0.011) and anxiety disorders
(p = 0.013), more comorbid disorders and lower functionality scores compared to
their native counterparts (p = 0.001). CONCLUSIONS: SGI children seem to have
higher rates of psychiatric disorders most probably due to migration-induced
burdens. The professionals treating SGI children should have more awareness for
these problems to be able to approach them in a culture and language sensitive
way.
PMID- 28498089
TI - Changes in BMI in hospitalized patients during treatment with antipsychotics,
depending on gender and other factors.
AB - OBJECTIVE: To investigate the differences in body mass index (BMI) changes
between men and women during hospitalization. METHODS: The retrospective study
monitored demographic and clinical data of 462 schizophrenic patients
hospitalized 737 times between 2006 and 2011. BMI analysis was performed on
patients on antipsychotic medication hospitalized longer than four days. RESULTS:
Patients with an initial BMI < 25 gained more weight than patients with a BMI >
25 (3.94% vs. 0.23%, men 4.02% vs. 0.69%, women 3.79% vs. -0.52%, always p <
0.001). Greater BMI gains were reported during the first hospitalization than
during subsequent ones (3.94% vs. 1.66%, men 3.97% vs. 1.98%, women 3.88% vs.
1.18%, always p < 0.001). The comparison between men and women showed a higher
increase in BMI in men 2.36% vs. 1.54%, p = 0.022. Men also gained significantly
more weight than women on polytherapy (+2.55% vs. +1.37%) and during subsequent
hospitalizations (1.98% vs. 1.18%). For treatment with various atypical
antipsychotics (AP), no significant differences were found in weight changes
between men and women; during treatment using a combination of multi-receptor AP
and metabolically neutral aripiprazole, a significant increase of BMI occurred in
men, but not in women (p = 0.018). CONCLUSIONS: Men appear to be more prone to
weight gain than women.
PMID- 28498090
TI - World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for
biological treatment of schizophrenia - a short version for primary care.
AB - OBJECTIVE: Schizophrenia is a severe mental disorder and many patients are
treated in primary care settings. Apart from the pharmacological management of
disease-associated symptoms, the detection and treatment of side effects is of
the utmost importance in clinical practice. The purpose of this publication is to
offer relevant evidence-based recommendations for the biological treatment of
schizophrenia in primary care. METHODS: This publication is a short and practice
oriented summary of Parts I-III of the World Federation of Societies of
Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of
Schizophrenia. The recommendations were developed by the authors and consented by
a task force of international experts. Guideline recommendations are based on
randomized-controlled trials and supplemented with non-randomized trials and meta
analyses where necessary. RESULTS: Antipsychotics of different chemical classes
are the first-line pharmacological treatments for schizophrenia. Specific
circumstances (e.g., suicidality, depression, substance dependence) may need
additional treatment options. The pharmacological and non-pharmacological
management of side effects is of crucial importance for the long-term treatment
in all settings of the healthcare system. CONCLUSIONS: This summary of the three
available evidence-based guidelines has the potential to support clinical
decisions and can improve treatment of schizophrenia in primary care settings.
PMID- 28498091
TI - Letter to the Editor. Endoscopic third ventriculostomy with choroid plexus
cauterization.
PMID- 28498092
TI - Barriers to ESC guideline implementation: results of a survey from the European
Council on Cardiovascular Nursing and Allied Professions (CCNAP).
AB - BACKGROUND: The European Society of Cardiology (ESC) has a comprehensive clinical
guideline development programme, relevant for all clinicians. However,
implementation of guidelines is not always optimal. AIM: The aim of this study
was to determine nurses' and allied professionals' awareness and barriers
regarding clinical guideline implementation. METHODS: A cross-sectional survey
was administrated online and in print at EuroHeartCare 2015. A questionnaire was
developed which examined awareness and barriers to implementation of ESC
guidelines on cardiovascular disease prevention in clinical practice (2012) and
ESC guidelines in general. RESULTS: Of the 298 respondents, 12% reported that the
prevention guidelines were used in their practice area. Respondents identified,
in order of magnitude, that lack of leadership, workload, time, resources and a
perception that they were unable to influence current practice were barriers to
the use of the prevention guidelines. When asked to rank barriers to use of any
ESC guidelines, time (22%) and leadership (23%) were ranked highest. CONCLUSIONS:
Implementation of ESC guidelines by nurses, the majority responders in this
survey, is a serious problem, requiring urgent improvement to ensure patients
receive optimal evidence based care. Issues of leadership, workload, time and
resources are significant barriers to guideline implementation. It is of concern
that these professionals perceive both that they have little influence on
implementation decisions and lack of leadership regarding guideline
implementation. Educational and organisational strategies to improve leadership
skills are imperative. These will build self-efficacy and empower nurses and
allied professionals to advocate for evidence-based care in the clinical
environment.
PMID- 28498093
TI - Cardiac tissue engineering: from matrix design to the engineering of bionic
hearts.
AB - The field of cardiac tissue engineering aims at replacing the scar tissue created
after a patient has suffered from a myocardial infarction. Various technologies
have been developed toward fabricating a functional engineered tissue that
closely resembles that of the native heart. While the field continues to grow and
techniques for better tissue fabrication continue to emerge, several hurdles
still remain to be overcome. In this review we will focus on several key advances
and recent technologies developed in the field, including biomimicking the
natural extracellular matrix structure and enhancing the transfer of the
electrical signal. We will also discuss recent developments in the engineering of
bionic cardiac tissues which integrate the fields of tissue engineering and
electronics to monitor and control tissue performance.
PMID- 28498094
TI - Predictors of all-cause 30 day readmission among Medicare patients with type 2
diabetes.
AB - OBJECTIVE: Readmission is costly among patients with type 2 diabetes (T2DM) in
Medicare Advantage Prescription Drug Plans; identifying high-risk patients is
necessary for targeting reduction programs. The objective of this study was to
develop a claims-based algorithm to predict all-cause 30 day readmission among
patients with T2DM. METHODS: This study used administrative data from 1 January
2012 through 31 January 2014. The cohort included hospitalized T2DM patients,
aged 18-90 with >=12 months' continuous enrollment before an unplanned hospital
admission and >=1 month of enrollment post-discharge, excluding patients in long
term care >30 days pre-index. Multivariate logistic regression predicted the
likelihood of readmission following hospitalization in 2013. The analytic file
was randomly split into training and test datasets to build and validate the
model. Candidate variables included physician and patient demographics, baseline
clinical conditions, and healthcare utilization metrics. Clinical conditions were
classified using the Healthcare Cost and Utilization Project clinical
classification system for ICD-9-CM. RESULTS: Of 63,237 individuals, 17.1%
experienced a readmission. Of nearly 200 candidate variables, 14 were predictors
of readmission, including total cumulative number of days for inpatient stays and
the number of emergency department visits in the baseline period. Male gender,
older age, and certain comorbidities were associated with higher likelihood of
readmission. The final model demonstrated good discriminant ability (c-statistic
= 0.82). CONCLUSIONS: This study provided evidence that certain patient
characteristics and healthcare utilization are predictive of readmission. An
algorithm with good discriminant ability was developed which could be used to
target readmission reduction programs. Physician gender, specialty, and ownership
status did not appear to influence the likelihood of readmission.
PMID- 28498095
TI - Risk factors for development of postoperative cerebellar mutism syndrome in
children after medulloblastoma surgery.
AB - OBJECTIVE Postoperative cerebellar mutism syndrome (pCMS) occurs in 7%-50% of
children after cerebellar tumor surgery. Typical features include a latent onset
of 1-2 days after surgery, transient mutism, emotional lability, and a wide
variety of motor and neurobehavioral abnormalities. Sequelae of this syndrome
usually persist long term. The principal causal factor is bilateral surgical
damage (regardless of tumor location) to any component of the proximal efferent
cerebellar pathway, which leads to temporary dysfunction of cerebral cortical
regions as a result of diaschisis. Tumor type, cerebellar midline location, and
brainstem involvement are risk factors for pCMS that have been identified
repeatedly, but they do not explain its latent onset. Ambiguous or negative
results for other factors, such as hydrocephalus, postoperative meningitis,
length of vermian incision, and tumor size, have been reached. The aim of this
study was to identify perioperative clinical, radiological, and laboratory
factors that also increase risk for the development of pCMS. The focus was on
factors that might explain the delayed onset of pCMS and thus might provide a
time window for taking precautionary measures to prevent pCMS or reduce its
severity. The study was focused specifically on children who had undergone
surgery for medulloblastoma. METHODS In this single-center retrospective cohort
study, the authors included 71 children with medulloblastoma, 28 of whom
developed pCMS after primary resection. Clinical and laboratory data were
collected prospectively and analyzed systematically. Variables were included for
univariate and multivariate analysis. RESULTS Univariate regression analysis
revealed 7 variables that had a significant influence on pCMS onset, namely,
tumor size, maximum tumor diameter > 5 cm, tumor infiltration or compression of
the brainstem, significantly larger decreases in hemoglobin (p = 0.010) and
hematocrit (p = 0.003) in the pCMS group after surgery than in the no-pCMS group,
significantly more reported incidents of severe bleeding in the tumor bed during
surgery in the pCMS group, preoperative hydrocephalus, and a mean body
temperature rise of 0.5 degrees C in the first 4 days after surgery in the pCMS
group. Multiple regression analysis revealed that tumor size, tumor infiltration
into or compression of the brainstem, and higher mean body temperature in the
first 4 postoperative days were independent and highly significant predictors for
pCMS. CONCLUSIONS The authors confirmed earlier findings that tumor-associated
preoperative conditions, such as a maximum tumor diameter >= 5 cm and
infiltration into or compression of the brainstem, are associated with a higher
risk for the development of pCMS. Most importantly, the authors found that a 0.5
degrees C higher mean body temperature in the first 4 postoperative days
increased the odds ratio for the development of pCMS almost 5-fold. These data
suggest that an important focus for the prevention of pCMS in children who have
undergone medulloblastoma surgery might be rigorous maintenance of normothermia
as standard care after surgery.
PMID- 28498096
TI - Characterization of the Anti-Bovine Podoplanin Monoclonal Antibody PMab-44.
AB - A type I transmembrane sialoglycoprotein podoplanin (PDPN) is expressed in
several normal cells, including podocytes of the kidney, type I alveolar cells of
the lung, and lymphatic endothelial cells. We recently produced an anti-bovine
PDPN (bovPDPN) monoclonal antibody (mAb), PMab-44, by immunizing mice with
recombinant proteins of bovPDPN. In this study, we determined the critical
epitope of PMab-44 for the recognition of bovPDPN using many deletion mutants and
point mutants of bovPDPN. Flow cytometric analyses revealed that the epitope of
PMab-44 was Glu46-Thr50, which corresponds to platelet aggregation-stimulating
(PLAG) domain-3. The important amino acids in the PMab-44 epitope were determined
to be Glu46, Tyr48, and Thr50. Western blot analysis also confirmed these
results, indicating that the PLAG domain of bovPDPN is also important in
immunogenicity for producing useful anti-PDPN mAbs.
PMID- 28498097
TI - The Asplenic Patient: Post-Insult Immunocompetence, Infection, and Vaccination.
AB - BACKGROUND: Splenic injury can occur through multiple mechanisms and may result
in various degrees of residual immunocompetence. Functionally or anatomically
asplenic patients are at higher risk for infection, particularly with
encapsulated bacteria. Vaccination is recommended to prevent infection with these
organisms; however, the recommendations are routinely updated, and vaccine
selection and timing are complex. METHODS: Review of the pertinent English
language literature, including the recommendations of the U.S. Centers for
Disease Control and Prevention's Advisory Committee on Immunization Practices.
RESULTS: Overwhelming post-splenectomy infection is associated with high
morbidity and mortality rates. Patients requiring splenectomy for trauma-related
injury appear to be at lower risk for infection than those undergoing splenectomy
for a hematologic or oncologic indication. Initial vaccination is dependent on
immunization history but generally should consist of the 13-valent pneumococcal
conjugate, quadrivalent meningococcal conjugate, meningococcal serogroup B, and
Haemophilus influenzae serotype b (Hib) vaccines. Antimicrobial prophylaxis for
certain asplenic patients, such as children under the age of five y, may be
indicated. CONCLUSION: Immunization remains a key measure to prevent overwhelming
post-splenectomy infection. Consideration of new recommendations and indications,
possible interactions, and timing remains important to including optimal response
to the vaccines.
PMID- 28498098
TI - Germinal center B cell development has distinctly regulated stages completed by
disengagement from T cell help.
AB - To reconcile conflicting reports on the role of CD40 signaling in germinal center
(GC) formation, we examined the earliest stages of murine GC B cell
differentiation. Peri-follicular GC precursors first expressed intermediate
levels of BCL6 while co-expressing the transcription factors RelB and IRF4, the
latter known to repress Bcl6 transcription. Transition of GC precursors to the
BCL6hi follicular state was associated with cell division, although the number of
required cell divisions was immunogen dose dependent. Potentiating T cell help or
CD40 signaling in these GC precursors actively repressed GC B cell maturation and
diverted their fate towards plasmablast differentiation, whereas depletion of
CD4+ T cells promoted this initial transition. Thus while CD40 signaling in B
cells is necessary to generate the immediate precursors of GC B cells, transition
to the BCL6hi follicular state is promoted by a regional and transient diminution
of T cell help.
PMID- 28498100
TI - Extraordinary effects of unnatural pairings.
AB - Engineered molecules based on human cytokines have potential uses in research and
medicine.
PMID- 28498099
TI - Synthekines are surrogate cytokine and growth factor agonists that compel
signaling through non-natural receptor dimers.
AB - Cytokine and growth-factor ligands typically signal through homo- or hetero
dimeric cell surface receptors via Janus Kinase (JAK/TYK), or Receptor Tyrosine
Kinase (RTK)-mediated trans-phosphorylation. However, the number of receptor
dimer pairings occurring in nature is limited to those driven by natural ligands
encoded within our genome. We have engineered synthethic cytokines (synthekines)
that drive formation of cytokine receptor dimer pairings that are not formed by
endogenous cytokines and that are not found in nature, and which activate
distinct signaling programs. We show that a wide range of non-natural cytokine
receptor hetero-dimers are competent to elicit a signaling output. We engineered
synthekine ligands that assembled IL-2Rbeta/IL-4Ralpha or IL-4Ralpha/IFNAR2
receptor heterodimers, that do not occur naturally, triggering signaling and
functional responses distinct from those activated by the endogenous cytokines IL
2, IL-4, and IFN. Furthermore, hybrid synthekine ligands that dimerized a
JAK/STAT cytokine receptor with a receptor tyrosine kinase (RTK) also elicited a
signaling response. Synthekines represent a new family of synthetic ligands with
pre-defined receptors, but 'orphan' functions, that enable the full combinatorial
scope of dimeric signaling receptors encoded within the human genome to be
exploited for basic research and drug discovery.
PMID- 28498101
TI - The evolution of gene regulation.
AB - The gene regulation mechanisms necessary for the development of complex
multicellular animals have been found in sponges.
PMID- 28498103
TI - A selectivity filter at the intracellular end of the acid-sensing ion channel
pore.
AB - Increased extracellular proton concentrations during neurotransmission are
converted to excitatory sodium influx by acid-sensing ion channels (ASICs). 10
fold sodium/potassium selectivity in ASICs has long been attributed to a central
constriction in the channel pore, but experimental verification is lacking due to
the sensitivity of this structure to conventional manipulations. Here, we
explored the basis for ion selectivity by incorporating unnatural amino acids
into the channel, engineering channel stoichiometry and performing free energy
simulations. We observed no preference for sodium at the "GAS belt" in the
central constriction. Instead, we identified a band of glutamate and aspartate
side chains at the lower end of the pore that enables preferential sodium
conduction.
PMID- 28498102
TI - Chimeric origins of ochrophytes and haptophytes revealed through an ancient
plastid proteome.
AB - Plastids are supported by a wide range of proteins encoded within the nucleus and
imported from the cytoplasm. These plastid-targeted proteins may originate from
the endosymbiont, the host, or other sources entirely. Here, we identify and
characterise 770 plastid-targeted proteins that are conserved across the
ochrophytes, a major group of algae including diatoms, pelagophytes and kelps,
that possess plastids derived from red algae. We show that the ancestral
ochrophyte plastid proteome was an evolutionary chimera, with 25% of its
phylogenetically tractable nucleus-encoded proteins deriving from green algae. We
additionally show that functional mixing of host and plastid proteomes, such as
through dual-targeting, is an ancestral feature of plastid evolution. Finally, we
detect a clear phylogenetic signal from one ochrophyte subgroup, the lineage
containing pelagophytes and dictyochophytes, in plastid-targeted proteins from
another major algal lineage, the haptophytes. This may represent a possible
serial endosymbiosis event deep in eukaryotic evolutionary history.
PMID- 28498104
TI - Modeling Hsp70/Hsp40 interaction by multi-scale molecular simulations and
coevolutionary sequence analysis.
AB - The interaction between the Heat Shock Proteins 70 and 40 is at the core of the
ATPase regulation of the chaperone machinery that maintains protein homeostasis.
However, the structural details of the interaction remain elusive and contrasting
models have been proposed for the transient Hsp70/Hsp40 complexes. Here we
combine molecular simulations based on both coarse-grained and atomistic models
with coevolutionary sequence analysis to shed light on this problem by focusing
on the bacterial DnaK/DnaJ system. The integration of these complementary
approaches resulted in a novel structural model that rationalizes previous
experimental observations. We identify an evolutionarily conserved interaction
surface formed by helix II of the DnaJ J-domain and a structurally contiguous
region of DnaK, involving lobe IIA of the nucleotide binding domain, the inter
domain linker, and the beta-basket of the substrate binding domain.
PMID- 28498105
TI - Intracellular uptake of macromolecules by brain lymphatic endothelial cells
during zebrafish embryonic development.
AB - The lymphatic system controls fluid homeostasis and the clearance of
macromolecules from interstitial compartments. In mammals brain lymphatics were
only recently discovered, with significant implications for physiology and
disease. We examined zebrafish for the presence of brain lymphatics and found
loosely connected endothelial cells with lymphatic molecular signature covering
parts of the brain without forming endothelial tubular structures. These brain
lymphatic endothelial cells (BLECs) derive from venous endothelium, are distinct
from macrophages, and are sensitive to loss of Vegfc. BLECs endocytose
macromolecules in a selective manner, which can be blocked by injection of
mannose receptor ligands. This first report on brain lymphatic endothelial cells
in a vertebrate embryo identifies cells with unique features, including the
uptake of macromolecules at a single cell level. Future studies will address
whether this represents an uptake mechanism that is conserved in mammals and how
these cells affect functions of the embryonic and adult brain.
PMID- 28498107
TI - Ultrasound-assisted thrombolysis of an occluded transjugular portosystemic shunt.
AB - Transjugular intrahepatic portosystemic shunt (TIPS) insertion is commonly
performed for refractory ascites or variceal bleeding. However, TIPS dysfunction
can be seen in both early and late settings, with shunt thrombosis a particular
problem. Treatment of shunt dysfunction commonly involves angioplasty and re
lining, with or without embolectomy, mechanical thrombectomy, or thrombolysis.
Ultrasound-assisted thrombolysis has been shown to be successful for treatment of
pulmonary embolism, deep vein thrombosis, and peripheral arterial
thromboembolism, but has not been described before for TIPS occlusion. Ultrasound
is theorized to lead to a shortened duration of thrombolysis due to thinning of
the fibrin clot and exposing plasminogen receptor sites. In this technical
report, we describe the first published use of ultrasound-assisted thrombolysis
in the declotting of an occluded TIPS. We found that the use of ultrasound
assisted thrombolysis allowed a relatively short duration of thrombolytic
therapy, with removal of thrombus extending into the portal vein, facilitating
stent re-lining. No complications were observed, in particular no bleeding
complications. The TIPS remains patent at 8 months postprocedure.
PMID- 28498106
TI - Kinetic modeling predicts a stimulatory role for ribosome collisions at
elongation stall sites in bacteria.
AB - Ribosome stalling on mRNAs can decrease protein expression. To decipher ribosome
kinetics at stall sites, we induced ribosome stalling at specific codons by
starving the bacterium Escherichia coli for the cognate amino acid. We measured
protein synthesis rates from a reporter library of over 100 variants that encoded
systematic perturbations of translation initiation rate, the number of stall
sites, and the distance between stall sites. Our measurements are quantitatively
inconsistent with two widely-used kinetic models for stalled ribosomes: ribosome
traffic jams that block initiation, and abortive (premature) termination of
stalled ribosomes. Rather, our measurements support a model in which collision
with a trailing ribosome causes abortive termination of the stalled ribosome. In
our computational analysis, ribosome collisions selectively stimulate abortive
termination without fine-tuning of kinetic rate parameters at ribosome stall
sites. We propose that ribosome collisions serve as a robust timer for
translational quality control pathways to recognize stalled ribosomes.
PMID- 28498109
TI - Ultra-stiff metallic glasses through bond energy density design.
AB - The elastic properties of crystalline metals scale with their valence electron
density. Similar observations have been made for metallic glasses. However, for
metallic glasses where covalent bonding predominates, such as metalloid metallic
glasses, this relationship appears to break down. At present, the reasons for
this are not understood. Using high energy x-ray diffraction analysis of melt
spun and thin film metallic glasses combined with density functional theory based
molecular dynamics simulations, we show that the physical origin of the ultrahigh
stiffness in both metalloid and non-metalloid metallic glasses is best understood
in terms of the bond energy density. Using the bond energy density as novel
materials design criterion for ultra-stiff metallic glasses, we are able to
predict a Co33.0Ta3.5B63.5 short range ordered material by density functional
theory based molecular dynamics simulations with a high bond energy density of
0.94 eV A-3 and a bulk modulus of 263 GPa, which is 17% greater than the stiffest
Co-B based metallic glasses reported in literature.
PMID- 28498108
TI - Imaging for abdominal involvement in amyloidosis.
AB - Involvement of the abdominal organs has variable presentations mostly without
specific findings. The objective of this pictorial essay was to illustrate the
computed tomography and magnetic resonance imaging (MRI) findings of abdominal
involvement in systemic amyloidosis. Heterogeneous appearance of the liver,
periportal involvement, diffuse low signal intensity of spleen on T2-weighted
MRI, and thickened bowel wall may be helpful imaging findings when accompanied by
presence or history of chronic inflammatory disease and clinical suspicion for
amyloidosis.
PMID- 28498110
TI - Solution synthesis of lead seeded germanium nanowires and branched nanowire
networks and their application as Li-ion battery anodes.
AB - Herein, we report the high density growth of lead seeded germanium nanowires
(NWs) and their development into branched nanowire networks suitable for
application as lithium ion battery anodes. The synthesis of the NWs from lead
seeds occurs simultaneously in both the liquid zone (solution-liquid-solid (SLS)
growth) and solvent rich vapor zone (vapor-liquid-solid (VLS) growth) of a high
boiling point solvent growth system. The reaction is sufficiently versatile to
allow for the growth of NWs directly from either an evaporated catalyst layer or
from pre-defined nanoparticle seeds and can be extended to allowing extensive
branched nanowire formation in a secondary reaction where these seeds are coated
onto existing wires. The NWs are characterized using TEM, SEM, XRD and DF-STEM.
Electrochemical analysis was carried out on both the single crystal Pb-Ge NWs and
the branched Pb-Ge NWs to assess their suitability for use as anodes in a Li-ion
battery. Differential capacity plots show both the germanium wires and the lead
seeds cycle lithium and contribute to the specific capacity that is approximately
900 mAh g-1 for the single crystal wires, rising to approximately 1100 mAh g-1
for the branched nanowire networks.
PMID- 28498111
TI - 55Mn NMR observation of colossal magnetoresistance effect in Sm0.55Sr0.45MnO3.
AB - Temperature dependent 55Mn NMR study of Sm0.55Sr0.45MnO3 is reported. Previous
bulk magnetization measurements have shown that below T C ~ 125 K the sample is
ferromagnetic metallic (FMM) and above TC it is charge ordered and insulating. In
present report, we show that from zero-field NMR a single line double-exchange
(DE) signal is observed at temperatures up to 139 K, which is due to a presence
of FMM clusters also above T C. The intensity of the DE line follows the
temperature dependence of the magnetization measured at 0.01 T. When a magnetic
field up to 2 T is applied at 139 K (i.e. 14 K above T C), a strong increase in
NMR intensity of the DE line is observed indicating that content of FMM regions
increases. This reveals that metallicity is induced in the material by the
applied magnetic field and explains the observed colossal magnetoresistance (CMR)
effect at the microscopic level. The observation agrees with previous results,
which confirm that the percolation of the FMM clusters is responsible for the CMR
effect. The shift of the resonant frequency in the applied field is three times
smaller compared to decrease expected from gyromagnetic ratio, which indicates an
antiferromagnetic coupling between the FMM clusters.
PMID- 28498112
TI - Effect of baffles on the hydraulic performance of sediment retention ponds.
AB - An investigation of the effect of baffles on retention pond performance using a
physical model of an existing sediment retention pond is presented. Analysis of
residence time (RTD curves) was used to compare the hydraulic performance of
different arrangements of baffles in the pond. Five different arrangements for
the design of baffles were studied. The results show that placing a single baffle
to deflect the influent to a sediment retention pond does not improve pond
performance; rather, it stimulates short-circuiting. This is contradictory to the
literature and is considered to be a consequence of the model pond incorporating
sloping walls, which is a novel aspect of this study. Most of the previous
studies have neglected the effects of battered walls. Conversely, the inclusion
of more than two baffles was found to increase the hydraulic performance. The
results reported here are limited to small and narrow ponds where a large portion
of the pond is batter (i.e. made up of sloping walls). For large area ponds,
batter effects may be negligible and are likely to be different from those
reported here.
PMID- 28498113
TI - A greenhouse gas source of surprising significance: anthropogenic CO2 emissions
from use of methanol in sewage treatment.
AB - The impact of methanol (CH3OH) as a source of anthropogenic carbon dioxide (CO2)
in denitrification at wastewater treatment plants (WWTPs) has never been
quantified. CH3OH is the most commonly purchased carbon source for sewage
denitrification. Until recently, greenhouse gas (GHG) reporting protocols
consistently ignored the liberation of anthropogenic CO2 attributable to CH3OH.
This oversight can likely be attributed to a simplifying notion that CO2 produced
through activated-sludge-process respiration is biogenic because most raw-sewage
carbon is un-sequestered prior to entering a WWTP. Instead, a biogenic
categorization cannot apply to fossil-fuel-derived carbon sources like CH3OH.
This paper provides a summary of how CH3OH use at DC Water's Blue Plains Advanced
Wastewater Treatment Plant (AWTP; Washington, DC, USA) amounts to 60 to 85% of
the AWTP's Scope-1 emissions. The United States Environmental Protection Agency
and Water Environment Federation databases suggest that CH3OH CO2 likely
represents one quarter of all Scope-1 GHG emissions attributable to sewage
treatment in the USA. Finally, many alternatives to CH3OH use exist and are
discussed.
PMID- 28498114
TI - Life cycle assessment of sludge management with phosphorus utilisation and
improved hygienisation in Sweden.
AB - To provide input to sewage sludge management strategies that address expected new
regulations in terms of hygienisation and phosphorus recovery in Sweden, an
environmental life cycle assessment (LCA) was made. The LCA identified
environmental hot spots for methods that may permit sludge or phosphorus from
sludge to be applied on agricultural land. In particular, thermophilic digestion,
pasteurisation, thermal hydrolysis, urea treatment and mono-incineration with
phosphorus recovery were compared. In addition, a sludge management system
involving drying of sludge before use in forestry was investigated. The results
showed that some major impacts are related to large uncertainties, such as those
related to emissions from sludge storage. It also showed that large gains can be
achieved when products from the systems replace other products, in particular
when biogas is used to replace natural gas in vehicles, but also when sludge is
used in agriculture and forestry. In general, there are small differences between
the sludge management methods. Retaining the sludge matrix to allow for its
utilisation in agriculture may conflict with keeping emissions to air and water
from the sludge matrix low. It is recommended that any sludge management option
minimises emissions from sludge to air and water and that resources are recovered
and used, in line with the principles of a circular economy.
PMID- 28498115
TI - Field campaign on sediment transport behaviour in a pressure main from pumping
station to wastewater treatment plant in Berlin.
AB - As part of the project KURAS, the Berliner Wasserbetriebe realized a field
campaign in 2015 in order to increase the process knowledge regarding the
behaviour of transported sediment in the pressure main leading from the
pumpstation to the wastewater treatment plant. The field campaign was conducted
because of a lack of knowledge about the general condition of the pressure main
due to its bad accessibility and the suspicion of deposits caused by hydraulic
underload. The practical evidence of the sediment transport performance of this
part of the sewer system, dependent on different load cases, should present a
basis for further analysis, for example regarding flushing measures. A positive
side-effect of the investigation was the description of the amount of pollutants
caused by different weather conditions in combined sewer systems and the
alterations of the sewage composition due to biogenic processes during transport.
The concept included the parallel sampling of the inflow at the pumpstation and
the outflow at the end of the pressure main during different weather conditions.
By calculating the inflow to the pressure main, as well as its outflow at
different flow conditions, it was possible to draw conclusions in regard to the
transport behaviour of sediment and the bioprocesses within an 8.5 km section of
the pressure main. The results show clearly that the effects of sedimentation and
remobilization depend on the flow conditions. The balance of the total suspended
solids (TSS) load during daily variations in dry weather shows that the
remobilization effect during the run-off peak is not able to compensate for the
period of sedimentation happening during the low flow at night. Based on the data
for dry weather, an average of 238 kg of TSS deposits in the pressure main
remains per day. The remobilization of sediment occurs only due to the abruptly
increased delivery rates caused by precipitation events. These high pollution
loads lead to a sudden strain at the wastewater treatment plant. It was found
that the sediment transport behaviour is characterized by sedimentation up to a
flow velocity of 0.35 m/s, while remobilization effects occur above 0.5 m/s. The
assumption of bad sediment transport performance in the pressure main was
confirmed. Therefore, the results can be used as a basis for further analysis,
for example regarding periodical flushing as a means of cleaning the pressure
main. The findings, especially regarding the methods and processes, are
transferable and can be applied to other pressure mains in combined sewer
systems. Besides the outlined evaluation of the sediment transport behaviour of
the pressure main, the collected data were used in the project to calibrate a
sewer system model, including a water quality model for the catchment area, and
as a contribution towards an early physically based sediment transport modelling
in InfoWorks CS.
PMID- 28498116
TI - Preparation of crosslinked chitosan magnetic membrane for cations sorption from
aqueous solution.
AB - A chitosan magnetic membrane was prepared in order to confer magnetic properties
to the membrane, which could be used for the removal of cations from aqueous
solution. The crosslinked magnetic membrane was compared with pristine chitosan
membrane in term of stability, morphology and cation adsorption capacity. The
fabricated magnetic materials are thermally stable as shown by thermogravimetric
curves. The membrane containing nickel magnetic particles (CHNiF-G) shows high
thermal stability compared to the other membranes. The Fourier transform infrared
spectroscopy showed successful preparation of chitosan magnetic membrane.
Scanning electron microscopy micrographs showed the rough surface of the membrane
with increased porosity. The prepared chitosan membranes were applied to cations
of copper, nickel and lead in dilute aqueous solution. The chitosan membrane
showed the following adsorption order for metallic cations: Cu2+ > Ni2+ > Pb2+,
while CHNiF-G showed higher capacity, 3.51 mmol g-1 for copper, reflecting the
improvement in adsorption capacity, since the amount of copper on pristine
chitosan gave 1.40 mmol g-1. The time required for adsorption to reach to the
equilibrium was 6 h for the selected cations using different chitosan membranes.
The kinetic study showed that adsorption followed pseudo-second order kinetics.
The most commonly used isotherm models, Freundlich, Langmuir and Temkin, were
applied to experimental data using linear regression technique. However, The
Temkin model fits better to experimental data.
PMID- 28498117
TI - Application of response surface methodology to optimize the fabrication of ZnCl2
activated carbon from sugarcane bagasse for the removal of Cu2.
AB - The present study focused on the application of response surface methodology to
optimize the fabrication of activated carbon (AC) from sugarcane bagasse for
adsorption of Cu2+ ion. The AC was synthesized via chemical activation with ZnCl2
as the activating agent. The central composite design based experiments were
performed to assess the individual and interactive effect of influential
parameters, including activation temperature, ZnCl2 impregnation ratio and
activation time on the AC yield and removal of Cu2+ ion from the aqueous
environment. The statistically significant, well-fitting quadratic regression
models were successfully developed as confirmed by high F- and low P-values
(<0.0001), high correlation coefficients and lack-of-fit tests. Accordingly, the
optimum AC yield and removal efficiency of Cu2+ were predicted, respectively, as
48.8% and 92.7% which were approximate to the actual values. By applying the
predicted optimal parameters, the AC shows a surprisingly high surface area of
around 1,500 m2/g accompanied by large pore volume and narrow micropore size at
low fabrication temperature.
PMID- 28498118
TI - Particle separation from road runoff by a decentralised lamella system -
laboratory tests and experiences in the field.
AB - A new decentralised settling system based on the principle of lamella separation
was developed for the treatment of road runoff. Two different laboratory test
methods, the DIBt (Deutsches Institut fur Bautechnik) procedure and our own
approach, were applied in order to evaluate the efficiency of the system based on
the separation of fine mineral particles and a mixture of mineral and organic
particles, respectively. Overall efficiencies (88% after DIBt and 61% according
to our own method) were comparable to results obtained for commercial systems.
The lamella system was then applied in the field for 1 year to treat runoff from
a road area of 420 m2. The amount of solids separated that was calculated from a
mass balance (10.1 kg) was consistent with the amount of sediments measured (8.6
kg). However, the average separation efficiency was only 30% in the field study.
This is related to the size and composition of the particles in runoff, which are
not represented well by the material used for the test procedures. It is
concluded that the test methods should be improved, and that more field studies
are needed in order to obtain a better understanding of the settling behaviour of
particles in road runoff.
PMID- 28498119
TI - Modeling of chromium (VI) adsorption from aqueous solutions using Jordanian
Zeolitic Tuff.
AB - The probable use of Jordanian natural zeolitic tuff in wastewater treatment as
natural adsorbent for the removal of Cr (VI) ions from aqueous solution in
continuous fixed bed columns was tested experimentally and theoretically. The
tested zeolitic tuff was obtained from Al Hala volcano (HZ) located in southern
part of Jordan and subjected to crushing and sieving only without any further
treatment. Experimentally the HZ grains were packed in a fixed bed column. The
used grain sizes are HZ1 (1.0-0.60 mm) and HZ2 (0.60-0.30 mm). The adsorption
capacity was evaluated using breakthrough curves and by applying the Thomas and
Yoon and Nelson models. The Thomas model analysis of the measured breakthrough
curves revealed that the adsorbent HZ2 has a higher adsorption capacity to Cr
(VI) ions (56.3 mg/g) than HZ1 (35.5 mg/g). The time elapsed to reach 50%
breakthrough was determined by the Yoon and Nelson model. The time to reach 50%
breakthrough is 318.78 min and 368.18 min for HZ1 and HZ2, respectively. The
research results indicate that the small size fraction (HZ2) is more suitable and
effective as adsorbent material than the size fraction (HZ1) due to its high
surface area.
PMID- 28498120
TI - Evaluation of statistical distributions to analyze the pollution of Cd and Pb in
urban runoff.
AB - Heavy metal pollution in urban runoff causes severe environmental damage.
Identification of these pollutants and their statistical analysis is necessary to
provide management guidelines. In this study, 45 continuous probability
distribution functions were selected to fit the Cd and Pb data in the runoff
events of an urban area during October 2014-May 2015. The sampling was conducted
from the outlet of the city basin during seven precipitation events. For
evaluation and ranking of the functions, we used the goodness of fit Kolmogorov
Smirnov and Anderson-Darling tests. The results of Cd analysis showed that
Hyperbolic Secant, Wakeby and Log-Pearson 3 are suitable for frequency analysis
of the event mean concentration (EMC), the instantaneous concentration series
(ICS) and instantaneous concentration of each event (ICEE), respectively. In
addition, the LP3, Wakeby and Generalized Extreme Value functions were chosen for
the EMC, ICS and ICEE related to Pb contamination.
PMID- 28498121
TI - Studies of selective adsorption, desorption and reuse of chemically altered
biomass produced from aquatic macrophytes for treatment of metal-containing
wastewater.
AB - The aquatic macrophytes Salvinia sp. and Pistia stratiotes have a natural
capacity to adsorb various elements, including heavy metals. This capacity was
enhanced with a chemical treatment using NaOH alkaline solution for Salvinia sp.
and a mixture of both Salvinia sp. and Pistia stratiotes at a proportion of 1:1,
whose respective biosorbents were called SSOH and MBOH. Adsorption tests were
done in a ternary system containing the metals copper, lead and manganese; the
parameters considered were: starting concentration, kinetics, pH and temperature.
The adsorption isotherms for SSOH had a maximum adsorptive capacity of 50.20,
53.85 and 14.68 mg g-1 for Cu, Pb and Mn, respectively; for MBOH, maximum values
were 44.62, 35.17 and 15.74 mg g-1 for Cu, Pb and Mn, respectively. The metals
displayed different behaviors with pH variation. The results also showed an
adsorption preference of Cu > Pb > Mn for SSOH. Desorption and readsorption
studies were also carried out, showing 100% desorption and increased adsorption
capacity in readsorption tests. Surface area and porosity analysis with the
Brunauer-Emmett-Teller (BET) method indicate that after chemical modification,
MBOH and SSOH biomasses had their surface increased in comparison to SS, with
values of 165.5657 (MBOH), 157.4392 (SSOH) and 78.9432 m2 g-1 (SS).
PMID- 28498122
TI - Optimization of adsorption process parameters by response surface methodology for
hexavalent chromium removal from aqueous solutions using Annona reticulata Linn
peel microparticles.
AB - Fruit peel microparticles of Annona reticulata Linn were used as biosorbent for
the sequestration of hexavalent chromium (CR(VI)). Characterization of the
biosorbent was done using scanning electron microscopy-energy dispersive X-ray
spectroscopy (SEM-EDXS), Fourier transfer infrared spectroscopy (FTIR), gas
chromatography-mass spectrometry (GCMS), carbon, hydrogen, nitrogen and sulphur
(CHNS) elemental analysis, mercury intrusion porosimetry and point of zero
charge. Influential parameters were optimized using response surface methodology
(RSM) with a total of 17 experimental runs based on the Box-Behnken design and
found to be pH 1.0, temperature 25 degrees C and 100 mg/L initial chromium
concentration. pH and concentration were found to be more influential than
temperature. The analysis of variance indicated that a second-order polynomial
regression equation was the most suitable for fitting the experimental data. The
experimental runs showed a good correlation with the predicted responses (R2 =
0.9956). The biosorption process fitted well with the Langmuir isotherm with an
adsorption capacity of 108. 32 mg/g out of the other isotherms such as Freundlich
and Dubinin-Radushkevich that were analyzed. Non linear pseudo first order,
pseudo second order, and intraparticle diffusion kinetics were applied to
describe the interaction between the biosorbent and Cr(VI). Desorption and
regeneration performances showed that fruit peels of Annona reticulata Linn can
be an environmental friendly option for hexavalent chromium removal from aqueous
solutions.
PMID- 28498123
TI - Comparison of phosphorus fraction distribution and influencing factors of
suspended and surface sediments in the Tiaoxi watershed, China.
AB - Suspended and surface sediments from the Tiaoxi watershed, fed by the Xitiaoxi
and Dongtiaoxi rivers, were analyzed for total phosphorus (TP) and the inorganic
P fractions of loosely adsorbed P that were extractable with NH4Cl (NH4Cl-P),
reductant P (BD-P), metal oxide-bound P extractable with NaOH (NaOH-P), and
calcium-bound, HCl-extractable P (HCl-P), while other physicochemical
compositions were also determined. The spatial variations of P fractions in these
sediments were investigated, and the major factors influencing the various
fractions were explored by multivariate statistics. Compared to surface
sediments, suspended sediments contained considerably higher concentrations of
total nitrogen, TP, organic matter, Al, Fe, Mn and biologically available P (BAP,
given as NH4Cl-P, BD-P and NaOH-P combined) and lower concentrations of Si, Ca
and HCl-P in the studied catchments. Dongtiaoxi sediments had higher TP,
inorganic phosphorus and HCl-P concentrations and a lower BAP content compared
with Xitiaoxi sediments, trends that were associated with local geological
backgrounds, landscapes and anthropogenic characteristics. The results of
principal component analysis showed different effects of sediment properties on P
fraction distributions for Xitiaoxi and Dongtiaoxi sediments. The sediment
components and structure exert a strong influence on BAP in Xitiaoxi sediments,
in contrast to Dongtiaoxi sediments, where P fractions are mainly affected by
urbanization and other anthropogenic activities such as shipping.
PMID- 28498124
TI - Treatment and potential reuse of greywater from schools: a pilot study.
AB - This study presented performance data on a low cost and easy maintenance pilot
system for on-site treatment and reuse of water collected from wash sinks and
fountains, as major sources of greywater (GW) at schools. Various treatment
options were studied including screening, sand filtration, chlorination, and UV
disinfection operated at different flow rates. Results showed that filtration
operated at low rates is very effective in total suspended solids (TSS) removal,
while UV proved to be more effective than chlorination for reduction of
biochemical oxygen demand (BOD), chemical oxygen demand (COD), and total
coliforms. Removal efficiencies up to 63%, 30% and 20% were obtained for TSS, COD
and BOD, respectively and reductions of log TC (CFU/100 ml) from 6.5 to 2 were
obtained at a filtration rate of 14 m3/d.m2. Treated effluent satisfied WHO
standards for reclaimed water reuse in landscape irrigation and toilet flushing.
The filtration-UV system is robust, showing the best and most reliable
performance for low and high strength GW treatment even under a 10-fold increase
in flow rate. A 5 m3/d pilot plant was developed for schools having 500 students
and detailed cost-benefit analysis indicated a net saving value, a surplus of
$1,600 per year, and pay back after 6 years and 11 months.
PMID- 28498125
TI - Examining the effects of urban agglomeration polders on flood events in Qinhuai
River basin, China with HEC-HMS model.
AB - The urban agglomeration polders type of flood control pattern is a general flood
control pattern in the eastern plain area and some of the secondary river basins
in China. A HEC-HMS model of Qinhuai River basin based on the flood control
pattern was established for simulating basin runoff, examining the impact of
urban agglomeration polders on flood events, and estimating the effects of
urbanization on hydrological processes of the urban agglomeration polders in
Qinhuai River basin. The results indicate that the urban agglomeration polders
could increase the peak flow and flood volume. The smaller the scale of the
flood, the more significant the influence of the polder was to the flood volume.
The distribution of the city circle polder has no obvious impact on the flood
volume, but has effect on the peak flow. The closer the polder is to basin
output, the smaller the influence it has on peak flows. As the level of
urbanization gradually improving of city circle polder, flood volumes and peak
flows gradually increase compared to those with the current level of urbanization
(the impervious rate was 20%). The potential change in flood volume and peak flow
with increasing impervious rate shows a linear relationship.
PMID- 28498126
TI - Modelling energy costs for different operational strategies of a large water
resource recovery facility.
AB - The main objective of this paper is to demonstrate the importance of applying
dynamic modelling and real energy prices on a full scale water resource recovery
facility (WRRF) for the evaluation of control strategies in terms of energy costs
with aeration. The Activated Sludge Model No. 1 (ASM1) was coupled with real
energy pricing and a power consumption model and applied as a dynamic simulation
case study. The model calibration is based on the STOWA protocol. The case study
investigates the importance of providing real energy pricing comparing (i) real
energy pricing, (ii) weighted arithmetic mean energy pricing and (iii) arithmetic
mean energy pricing. The operational strategies evaluated were (i) old versus new
air diffusers, (ii) different DO set-points and (iii) implementation of a carbon
removal controller based on nitrate sensor readings. The application in a full
scale WRRF of the ASM1 model coupled with real energy costs was successful.
Dynamic modelling with real energy pricing instead of constant energy pricing
enables the wastewater utility to optimize energy consumption according to the
real energy price structure. Specific energy cost allows the identification of
time periods with potential for linking WRRF with the electric grid to optimize
the treatment costs, satisfying operational goals.
PMID- 28498127
TI - Accelerated anaerobic release of K, Mg and P from surplus activated sludge for
element recovery and struvite formation inhibition.
AB - Accelerated release of potassium (K), magnesium (Mg) and phosphorus (P) from
surplus activated sludge (SAS) was investigated to develop a new system for the
recovery of the elements. Anaerobic cultivation of SAS during 24 h released 78%
of K and about 50% of Mg and P from SAS more effectively compared to aerobic
cultivation (K: 40%, Mg: 15%, P: 15%). Furthermore, the addition of sodium
acetate as an organic carbon source remarkably accelerated the release of K, Mg
and P from SAS under anaerobic condition. However, no increase in the maximum
release efficiencies was observed. The elements released from SAS could be
transferred to separate liquid with the existing mechanical thickener and be
recovered as MgKPO4 by some additional process. Furthermore, the removal of the
elements from SAS would inhibit the formation of struvite causing the blockage of
sludge transport pipe after anaerobic digestion process of thickened sludge.
PMID- 28498128
TI - Multi-parameter based coagulant dosing control.
AB - The required coagulant dosage is strongly related to the quality of raw water or
wastewater. Online sensors for most quality parameters are now readily available
to treatment facilities, yet remain rarely used in treatment process control.
This paper presents the evaluation of an advanced coagulant dosing control system
based on online measurements in full-scale processes. The popular multivariate
analytical method, partial least square regression, was used to build up the
relationship between the coagulant dose and wastewater quality. The system was
tested in two wastewater treatment plants (WWTPs) in Norway. Coagulant savings up
to 30% in Norwegian plants were observed with feed forward calibrations. The
considerable savings reduce sludge production, leading to further cost saving on
sludge treatment. This paper presents the method, function and experiences of the
full-scale implementation of the system in different WWTPs.
PMID- 28498129
TI - Photodegradation of diclofenac in aqueous solution by simulated sunlight
irradiation: kinetics, thermodynamics and pathways.
AB - Diclofenac (DCF) is one of the most frequently detected pharmaceuticals in
various water samples. This paper studied the effects of aquatic environmental
factors (pH, temperature and dissolved organic matter) on photodegradation of DCF
under simulated sunlight. The results demonstrate that degradation pathways
proceed via pseudo first-order kinetics in all cases and the photodegradation of
DCF by simulated sunlight. Thermodynamic study indicated that the
photodegradation course is spontaneous, exothermic and irreversible. The rate
constant gradually increased when the pH increased from 3 to 5, then decreased
when the pH increased from 5 to 8, and finally increased when the pH further
increased from 8 to 12. Humic acid inhibited the photodegradation of DCF. Three
kinds of main degradation products were observed by high performance liquid
chromatography/mass spectrometry and the degradation pathways were suggested. A
toxicity test using Photobacterium phosphoreum T3 Sp indicated the generation of
some more toxic products than DCF.
PMID- 28498130
TI - Comparison of in situ DGT measurement with ex situ methods for predicting cadmium
bioavailability in soils with combined pollution to biotas.
AB - To assess the capabilities of the different techniques in predicting Cadmium (Cd)
bioavailability in Cd-contaminated soils with the addition of Zn, one in situ
technique (diffusive gradients in thin films; DGT) was compared with soil
solution concentration and four widely used single-step extraction methods
(acetic acid, EDTA, sodium acetate and CaCl2). Wheat and maize were selected as
tested species. The results demonstrated that single Cd-polluted soils inhibited
the growth of wheat and maize significantly compared with control plants; the
shoot and root biomasses of the plants both dropped significantly (P < 0.05). The
addition of Zn exhibited a strong antagonism to the physiological toxicity
induced by Cd. The Pearson correlation coefficient presented positive
correlations (P < 0.01, R > 0.9) between Cd concentrations in two plants and Cd
bioavailability indicated by each method in soils. Consequently, the results
indicated that the DGT technique could be regarded as a good predictor of Cd
bioavailability to plants, comparable to soil solution concentration and the four
single-step extraction methods. Because the DGT technique can offer in situ data,
it is expected to be widely used in more areas.
PMID- 28498131
TI - Pre-treatment of thickened waste activated sludge (TWAS) for enhanced biogas
production via the application of a novel radial horn sonication technology.
AB - The efficacy of sonication as a pre-treatment to anaerobic digestion (AD) was
assessed using thickened waste activated sludge (TWAS). Efficiency was measured
in relation to solubilisation, dewaterability, and AD performance. Eighteen
experimental conditions were evaluated at low frequency (20 kHz), duration (2-10
s), amplitude (~8-12 MUm) and applied pressure (0.5-3.0 barg), using a sonixTM
patented titanium sonoprobe capable of delivering an instantaneous power of ~6 kW
provided by Doosan Enpure Ltd (DEL). An optimised experimental protocol was used
as a pre-treatment for biochemical methane potential (BMP) testing and semi
continuous trials. Four digesters, with a 2-L working volume were operated
mesophilically (37 +/- 0.5 degrees C) over 22 days. The results showed that the
sonixTM technology delivers effective sonication at very short retention times
compared to conventional system. Results demonstrate that the technology
effectively disrupts the floc structures and filaments within the TWAS, causing
an increase in solubilisation and fine readily digestible material. Both BMP
tests and semi-continuous trials demonstrated that sonicated TWAS gave higher
biodegradability and methane potential compared to untreated TWAS. Partial-stream
sonication (30:70 sonicated to untreated TWAS) resulted in a proportionate
increase in biogas production illustrating the benefits of full-stream
sonication.
PMID- 28498132
TI - Nitrate adsorption from aqueous solutions by calcined ternary Mg-Al-Fe
hydrotalcite.
AB - Calcined ternary hydrotalcite like compounds had been synthesized by co
precipitation and calcined at 450 degrees C for 6 h. It had been applied into
the nitrate removal from aqueous solutions. Various factors during adsorption
process, such as chemical composition of adsorbents, adsorbent dosage, initial
concentration of nitrate, initial pH and co-existing anions on nitrate adsorption
had been investigated. It was found that 1.5 g/L CHTlcs (Mg/Al/Fe molar ratio =
3:0.1:0.9) could achieve ideal adsorption efficiency at an initial nitrate
concentration of 100 mg/L. The value of pH had little effect on nitrate
adsorption. The co-existing anions had the inhibitory effect on nitrate
adsorption, which was in the order of PO43- > SO42- > Cl- > ClO4-. The batch
adsorption studies showed that experimental data were well described by the
pseudo-second-order kinetic model and Langmuir isotherm model, and the maximum
isotherm adsorption capacity was 123.305 mg/g. The adsorption of nitrate was a
spontaneous exothermic process with the reduction of entropy. The proposed
adsorption mechanism obtained from characterization was that CHTlcs uptake
nitrate through reconstruction effect and adsorption on external surface.
PMID- 28498133
TI - Numerical and experimental study of the fundamental flow characteristics of a 3D
gully box under drainage.
AB - Numerical studies regarding the influence of entrapped air on the hydraulic
performance of gullies are nonexistent. This is due to the lack of a model that
simulates the air-entrainment phenomena and consequently the entrapped air. In
this work, we used experimental data to validate an air-entrainment model that
uses a Volume-of-Fluid based method to detect the interface and the Shear-stress
transport k-omega turbulence model. The air is detected in a sub-grid scale,
generated by a source term and transported using a slip velocity formulation.
Results are shown in terms of free-surface elevation, velocity profiles,
turbulent kinetic energy and discharge coefficients. The air-entrainment model
allied to the turbulence model showed a good accuracy in the prediction of the
zones of the gully where the air is more concentrated.
PMID- 28498134
TI - Nanoscale Fe/Ag particles activated persulfate: optimization using response
surface methodology.
AB - This work studied the bimetallic nanoparticles Fe-Ag (nZVI-Ag) activated
persulfate (PS) in aqueous solution using response surface methodology. The Box
Behnken design (BBD) was employed to optimize three parameters (nZVI-Ag dose,
reaction temperature, and PS concentration) using 4-chlorophenol (4-CP) as the
target pollutant. The synthesis of nZVI-Ag particles was carried out through a
reduction of FeCl2 with NaBH4 followed by reductive deposition of Ag. The
catalyst was characterized by X-ray diffraction (XRD), scanning electron
microscopy (SEM) and Brunauer-Emmett-Teller (BET) surface area. The BBD was
considered a satisfactory model to optimize the process. Confirmatory tests were
carried out using predicted and experimental values under the optimal conditions
(50 mg L-1 nZVI-Ag, 21 mM PS at 57 degrees C) and the complete removal of 4-CP
achieved experimentally was successfully predicted by the model, whereas the
mineralization degree predicted (90%) was slightly overestimated against the
measured data (83%).
PMID- 28498135
TI - Removal of toxic Congo red dye from water employing low-cost coconut residual
fiber.
AB - The coconut residual fiber (CRF) is the major byproduct obtained during
production of virgin coconut oil. Its application as a biosorbent for adsorption
of Congo red was investigated. The CRF was subjected to different pretreatments,
namely, pressure cooking, hexane treatment, acid treatment and their
combinations. The pretreatment of CRF with the combination of hexane, acid, and
pressure cooking resulted in the highest degree of adsorption. The equilibrium
data were analyzed and found to fit best to both Langmuir and Freundlich
isotherms. Thermodynamic parameters such as standard free energy (DeltaG0 kJ mol
1), standard enthalpy (DeltaH0, kJ mol-1) and standard entropy (DeltaS0, kJ mol-1
K-1) of the systems were calculated by using the Langmuir constant. The DeltaG0,
DeltaH0 and DeltaS0 were found to be 16.51 kJ mol-1, -19.39 kJ mol-1 and -0.12 kJ
mol-1 K-1, respectively, at 300 K. These thermodynamic parameters suggest the
present adsorption process to be non-spontaneous and exothermic. The adsorption
process was observed to follow pseudo-second-order kinetics. The results suggest
that CRF has potential to be a biosorbent for the removal of hazardous material
(Congo red dye) with a maximum adsorption capacity of 128.94 mg g-1 at 300 K.
PMID- 28498136
TI - Gunshot Wound in an 18-Year-Old Woman, Inflicted With a Hunting Weapon Through an
Obstacle (Mobile Phone): Reconstruction of Events.
AB - The article presents a case of an 18-year-old woman wounded by a shot fired from
a distance with a hunting weapon. Because the location of the entrance and exit
wounds initially seemed inconsistent with the reports (both wounds were described
as "large and irregular in shape") and no photographs documenting the inflicted
injuries were taken, the case was referred for an opinion to the Department of
Forensic Medicine in Lodz. After a review of the medical records, radiology, the
victim's clothing, and performance of an experiment using the gun and ammunition,
it was established that the entrance wound was located on the abdomen, and the
exit wound was located on the buttock. The initial problems with recognizing the
entrance and exit wounds encountered by the surgical team were caused by bullet
deformation. Before hitting the body, the projectile pierced a mobile phone that
was in the pocket of the woman's jacket, subsequently causing a large atypical
secondary entrance wound. The experiment confirmed that, when the projectile
passed through an obstacle with consequent deformation, it caused more extensive
gunshot wounds, both at the entrance and at the exit, as well as more severe
damage to the bones.
PMID- 28498137
TI - Physical and Organizational Job Stressors in Pregnancy and Associations With
Primary Cesarean Deliveries.
AB - OBJECTIVE: The aim of this study was to assess the relationship between exposure
to physical and organizational job stressors during pregnancy and cesarean
delivery. METHODS: We sampled 580 employed women in California who participated
in a nested population-based case-control study of birth outcomes. Adjusted
multivariate regression analyses estimated associations between heavy lifting,
frequent bending, high noise, extreme temperature, prolonged standing and
organizational stressors (shift work, inflexible schedules, effort-reward ratio),
and primary cesarean (vs vaginal) delivery, controlling for covariates. RESULTS:
Women occupationally exposed had higher odds of cesarean. Those exposed to daily
manual lifting more than 15 pounds [adjusted odds ratio = 2.54; 95% confidence
interval (95% CI) 1.21 to 5.32] and at least four physical job stressors
(adjusted odds ratio = 3.49; 95% CI 1.21 to 10.09) had significantly elevated
odds of cesarean delivery. Exposed morbid women experienced greater risk; risk
was lower among those with schedule flexibility. CONCLUSION: Associations were
found between modifiable exposure to physical job stressors during pregnancy and
cesarean delivery.
PMID- 28498138
TI - Epidural Injection of Platelet Rich Plasma for Postlumbar Puncture Headaches.
PMID- 28498139
TI - JNA Journal Club.
PMID- 28498140
TI - Effect of Albumin in Combination With Mannitol on Whole-blood Coagulation In
Vitro Assessed by Thromboelastometry.
AB - BACKGROUND: Albumin and mannitol may interfere with hemostasis, but their
coinfluence is unclear. We aimed to determine the effects of albumin alone and in
combination with mannitol or Ringer acetate (RAC) on hemostasis in crossover in
vitro study. MATERIALS AND METHODS: From citrated fresh whole blood withdrawn
from 10 volunteers, we prepared 2.5, 5, 10, 15, and 20 vol% dilutions of 4%
albumin (Alb group). Each sample was thereafter diluted by 15% mannitol (Alb/Man
group) or RAC (Alb/RAC group) at a ratio of 9:1. Using thromboelastometry, FibTEM
(fibrinogen ROTEM) and ExTEM (extrinsic ROTEM) tests were performed. RESULTS: A
20 vol%, but not 2.5 to 15 vol% dilution of albumin caused a prolonged clot
formation time, alpha-angle decrease, and maximum clot firmness (MCF) weakening
compared with undiluted sample (P<0.05). Clot formation time prolonged more in
Alb5/Man than in Alb5 and Alb5/RAC dilution (P<0.05). In Alb2.5/Man, Alb10/Man,
and Alb15/Man, dilution alpha-angle was lower than in corresponding Alb/RAC and
Alb-group dilutions (P<0.05). In ExTEM, MCF decreased similarly in every dilution
of Alb/Man and Alb/RAC compared with Alb group (P<0.05). In FibTEM, MCF decreased
more in Alb10/Man than in Alb10/RAC dilution (P<0.05). CONCLUSIONS: In up to 15
vol% dilutions, albumin alone did not impair hemostasis in vitro, but in
combination with mannitol or RAC coagulation was disturbed similarly at most
concentrations. There was some significant additional effect with mannitol at
certain concentrations. Our results indicate that coadministration of mannitol
and albumin needs further study in vivo.
PMID- 28498141
TI - The ASA Committee for Neuroanesthesia and Anesthesia Quality Institute: Report
for Demographic Patterns for Neurosurgical Anesthesia Practice in the United
States.
PMID- 28498142
TI - Inflammatory Myopathy and Axonal Neuropathy in a Patient With Melanoma Following
Pembrolizumab Treatment.
AB - Immune-mediated adverse effects of immune checkpoint inhibitors are rather
common, but neuromyopathic immune-related adverse events are very rare. In this
report, we present a unique case of a patient with a complex neuromyopathic
syndrome with axonal neuropathy and inflammatory myopathy after a single dose of
pembrolizumab. An 82-year-old patient with a previously untreated stage IIIc
melanoma developed ptosis in the left eye, generalized weakness, and neck and
shoulder pain 15 days after pembrolizumab administration. He had left-sided
ptosis and miosis, with a normal pupillary light reflex, horizontal diplopia, and
voice hoarseness, along with weakness of the neck muscles and a hypokinetic right
vocal cord at laryngoscopy. The laboratory evaluation was remarkable for the
marked increase in the serum lactate dehydrogenase and creatine phosphokinase
levels. Further evaluation revealed findings compatible with axonal neuropathy
and inflammatory myopathy. The patient was treated with corticosteroids,
immunoglobulin, and plasmapheresis, with a minor response; the patient eventually
died. This case represents a newly described syndrome probably associated with
pembrolizumab administration.
PMID- 28498143
TI - The Crucible simulation: Behavioral simulation improves clinical leadership
skills and understanding of complex health policy change.
AB - BACKGROUND: The Health and Social Care Act 2012 represents the most complex
National Health Service reforms in history. High-quality clinical leadership is
important for successful implementation of health service reform. However, little
is known about the effectiveness of current leadership training. PURPOSE: This
study describes the use of a behavioral simulation to improve the knowledge and
leadership of a cohort of medical doctors expected to take leadership roles in
the National Health Service. METHODOLOGY: A day-long behavioral simulation (The
Crucible) was developed and run based on a fictitious but realistic health
economy. Participants completed pre- and postsimulation questionnaires generating
qualitative and quantitative data. Leadership skills, knowledge, and behavior
change processes described by the "theory of planned behavior" were self-assessed
pre- and postsimulation. RESULTS: Sixty-nine medical doctors attended.
Participants deemed the simulation immersive and relevant. Significant
improvements were shown in perceived knowledge, capability, attitudes, subjective
norms, intentions, and leadership competency following the program. Nearly one
third of participants reported that they had implemented knowledge and skills
from the simulation into practice within 4 weeks. CONCLUSIONS: This study
systematically demonstrates the effectiveness of behavioral simulation for
clinical management training and understanding of health policy reform. Potential
future uses and strategies for analysis are discussed. PRACTICE IMPLICATIONS:
High-quality care requires understanding of health systems and strong leadership.
Policymakers should consider the use of behavioral simulation to improve
understanding of health service reform and development of leadership skills in
clinicians, who readily adopt skills from simulation into everyday practice.
PMID- 28498144
TI - The Impact of Preexposure Prophylaxis Among Men Who Have Sex With Men: An
Individual-Based Model.
AB - OBJECTIVES: Preexposure prophylaxis (PrEP) is recommended for preventing HIV
infection among individuals at high risk, including men who have sex with men
(MSM). Although its individual-level efficacy is proven, questions remain
regarding population-level impact of PrEP implementation. DESIGN: We developed an
agent-based simulation of HIV transmission among MSM, accounting for
demographics, sexual contact network, HIV disease stage, and use of
antiretroviral therapy. We use this framework to compare PrEP delivery strategies
in terms of impact on HIV incidence and prevalence. RESULTS: The projected
reduction in HIV incidence achievable with PrEP reflects both population-level
coverage and individual-level adherence (as a proportion of days protected
against HIV transmission). For example, provision of PrEP to 40% of HIV-negative
MSM reporting more than one sexual partner in the last 12 months, taken with
sufficient adherence to provide protection on 40% of days, can reduce HIV
incidence by 9.5% (95% uncertainty range: 8%-11%) within 5 years. However, if
this could be increased to 80% coverage on 80% of days (eg, through mass
campaigns with a long-acting injectable formulation), a 43% (42%-44%) reduction
in HIV incidence could be achieved. Delivering PrEP to MSM at high risk for HIV
acquisition can augment population-level impact up to 1.8-fold. CONCLUSIONS: If
highly ambitious targets for coverage and adherence can be achieved, PrEP can
substantially reduce HIV incidence in the short-term. Although the reduction in
HIV incidence largely reflects the proportion of person-years protected, the
efficiency of PrEP delivery can be enhanced by targeting high-risk populations.
PMID- 28498145
TI - Brief Report: Progression of Atherosclerosis in HIV-Infected Individuals
Prospective Data From an Asian Cohort.
AB - BACKGROUND: The magnitude and risk factors of progression of atherosclerosis in
Asian HIV-infected individuals were unknown. This study aimed to evaluate: (1)
the rate of progression of atherosclerosis in HIV-infected individuals, and (2)
metabolic and inflammatory parameters that may predict atherosclerosis
progression in HIV-infected individuals in an Asian cohort. SETTING: A
prospective, longitudinal study was performed among adults attending an HIV
Metabolic clinic in Hong Kong. METHODS: Carotid intima media thickness (cIMT) was
measured at baseline and 24 months. Body composition, metabolic, and inflammatory
biomarkers [including homeostasis model assessment of insulin resistance, LDL
(low-density lipoprotein) cholesterol particle size, high-sensitive C reactive
protein, adiponectin] associated with cIMT change were analyzed; their predictive
performances were estimated using receiver operating characteristic analyses.
RESULTS: Sixty-one HIV-infected individuals (mean +/- SD age 49.8 +/- 11.4 years,
89% men, 97% Chinese, diabetes 39%, hypertension 30%, and dyslipidemia 85%) were
recruited. Annual rate of change of cIMT was +0.0075 (0.0000-0.0163) mm/yr, and
19% developed new plaque at 24 months. Two patients died during the study period,
1 because of sudden cardiac death. Using receiver operating characteristic
analyses, combination of lower limb fat percentage, LDL cholesterol subclass
pattern B, and lower adiponectin level, but not Framingham score, predicted
greater cIMT progression in HIV-infected individuals. CONCLUSIONS: Asian HIV
infected individuals had atherosclerosis progression. Limb fat percentage, LDL
cholesterol particle size, and adiponectin level may identify at-risk Asian HIV
infected individuals for early intervention.
PMID- 28498146
TI - First-Line Antiretroviral Treatment Outcomes and Durability in HIV-Infected
Children Treated Through the Universal Coverage Health Program in Thailand.
AB - BACKGROUND: We assessed the treatment outcomes on first-line antiretroviral
therapy (ART), and factors associated with switching regimen in HIV-infected
children treated through the universal coverage health program (UC) in Thailand.
METHODS: Children aged <15 years at ART initiation who had been receiving ART for
at least 6 months between 2008 and 2014 through UC were included in the analysis.
The Kaplan-Meier method was used to estimate immunological recovery (IMR),
immunological failure, and virological failure (VF). Cox models were used to
assess predictors of IMR and VF. Competing risk models were used to assess
factors associated with switching to a second-line regimen, with death considered
as a competing risk. RESULTS: A total of 4120 children initiated ART at a median
(interquartile range) age of 9.3 (5.8-12.0) years. The median duration of ART was
3.7 years with 17,950 person-years of follow-up. Two thousand eight hundred five
children achieved IMR, and the probability of IMR increased to 76% by 3 years
after ART initiation. Among 1054 children switched to second-line regimens, 84%
had VF and 19% had immunological failure. The cumulative rate of switching
regimen increased from 4% to 20% from 1 to 3 years after treatment. Children aged
>=12 years at ART initiation, starting with nonnucleoside reverse-transcriptase
inhibitors, and baseline CD4% <10% had an increased risk of switching to second
line regimens. CONCLUSIONS: Children receiving ART through UC had good treatment
outcomes, although a fifth required switching regimen by 3 years. Earlier
treatment initiation and avoiding nonnucleoside reverse-transcriptase inhibitor
first-line regimens in high-risk children may prevent treatment failure.
PMID- 28498147
TI - Reply.
PMID- 28498148
TI - Striatal activity is modulated by target probability.
AB - Target probability has well-known neural effects. In the brain, target
probability is known to affect frontal activity, with lower probability targets
producing more prefrontal activation than those that occur with higher
probability. Although the effect of target probability on cortical activity is
well specified, its effect on subcortical structures such as the striatum is less
well understood. Here, I examined this issue and found that the striatum was
highly responsive to target probability. This is consistent with its hypothesized
role in the gating of salient information into higher-order task representations.
The current data are interpreted in light of that fact that different components
of the striatum are sensitive to different types of task-relevant information.
PMID- 28498149
TI - Inhibition of glutamate release by cilnidipine in rat cerebrocortical nerve
terminals (synaptosomes).
AB - Cilnidipine is an antihypertensive drug that was reported to have a
neuroprotective profile. The present study aimed to investigate the effect of
cilnidipine on the 4-aminopyridine (4-AP)-induced glutamate release in the rat
cerebral cortex using isolated nerve terminals (synaptosomes). Cilnidipine
reduced the release of glutamate release induced by 4-AP in a concentration
dependent manner. This inhibitory effect was associated with a reduction in the 4
AP-induced intrasynaptosomal Ca concentration elevation and was not because of an
alteration of the synaptosomal membrane potential. The inhibition of glutamate
release by cilnidipine was markedly reduced or eliminated in the presence of the
Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel blocker omega-conotoxin MVIIC and
the protein kinase A inhibitor H89. The intracellular Ca-release inhibitors
dantrolene and CGP37157, the mitogen-activated protein kinase inhibitor PD98059
or the protein kinase C inhibitor GF109203X failed to affect the action of
cilnidipine. These results suggest that cilnidipine inhibits glutamate release
from rat cortical synaptosomes through the suppression of presynaptic voltage
dependent Ca entry and protein kinase A activity.
PMID- 28498150
TI - Effect of insulin on spatial memory in aluminum chloride-induced dementia in
rats.
AB - Latest reports suggest the involvement of insulin in modulating memory. A few
published in-vitro studies favor the antidementia effect of insulin. Thus, the
present study aimed to evaluate the prophylactic role of insulin and its
combination with glucose and its possible mechanism(s) in an aluminum chloride
(AlCl3)-induced cognitive dysfunction model in rodents, with a special focus on
memory centers namely, the hippocampus and the frontal cortex. Male Wistar rats
were exposed to AlCl3 (175 mg/kg orally) for 60 days. Insulin (0.5 IU/kg),
Insulin (0.5 IU/kg) in combination with glucose (200 mg/kg), and rivastigmine (1
mg/kg) were administered intraperitoneally 45 min before the administration of
AlCl3 for 60 days. Spatial memory was assessed using the Morris water-maze test.
After 60 days of treatment, animals were killed, and the hippocampus and frontal
cortex were collected and analyzed for acetylcholinesterase activity and
antioxidant enzyme level. Blood glucose levels were also analyzed. Treatment with
the standard drug, rivastigmine (1 mg/kg), produced a significant reduction in
escape latency and increased the time spent in the target quadrant compared with
the AlCl3-treated group. Insulin and its combination with glucose could not
inhibit the behavioral impairments in aluminum-exposed rats. Treatment with
insulin alone and its combination with glucose reversed the increased glucose
levels. Insulin alone and its combination with glucose could not inhibit aluminum
induced oxidative stress and impaired cholinergic transmission in the hippocampus
and frontal cortex regions. The study suggests the inability of prophylactic
insulin administration against cognitive dysfunction induced by environmental
toxin (AlCl3) in the hippocampus and the frontal cortex.
PMID- 28498152
TI - Oligoclonal T-cell Receptor Repertoire in Colonic Biopsies of Patients with
Microscopic Colitis and Ulcerative Colitis.
AB - BACKGROUND: Microscopic colitis (MC), comprising collagenous colitis (CC) and
lymphocytic colitis (LC), is a type of variation of inflammatory bowel diseases.
Local T-cell infiltration in the mucosa plays a major role in MC immunopathology.
METHODS: To understand diversity and clonality of infiltrating T cells, we
analyzed the T-cell receptor beta (TCRbeta) chains in colonic biopsies of MC,
ulcerative colitis (UC), and their remission counterparts (CC/LC-HR [histological
remission] or UC-R [remission]) compared with patients with noninflamed colons
using next-generation sequencing. RESULTS: Compared with controls and patients
with CC, patients with LC had significantly lower diversity with significantly
lower evenness and richness in TCRVbeta-Jbeta gene segments. Similarly, patients
with LC-HR had lower diversity because of significantly lower TCRVbeta-Jbeta
clone richness. Patients with UC and UC-R showed significantly higher diversity
and richness. Univariate and multivariate analyses were performed to identify
TCRVbeta-Jbeta gene segments differentiating disease types from controls or their
remission counterparts. Patients with LC were discriminated from controls by 12
clones and from patients with CC by 8 clones. Neither univariate nor multivariate
analyses showed significance for patients with CC or CC-HR compared with
controls. Patients with UC and UC-R had 16 and 14 discriminating clones,
respectively, compared with controls. CONCLUSIONS: Altogether, patients with MC
and UC showed an oligoclonal TCRbeta distribution. TCRVbeta-Jbeta clone types and
their diversity were distinctive between patients with CC and LC, as well as for
patients with UC, suggesting different pathophysiological mechanisms according to
disease type and stage. This study suggests that CC and LC are different entities
because of differences in immunoregulatory responses, as mirrored by their T-cell
repertoire.
PMID- 28498153
TI - Infliximab Trough Levels at Induction to Predict Treatment Failure During
Maintenance.
AB - BACKGROUND: Infliximab (IFX) is indicated for the treatment of inflammatory bowel
diseases (IBD). Nevertheless, loss of response (LOR) to IFX is reported in up to
10% to 30% of patients within the first year of treatment. Our objective was to
evaluate the impact of the pharmacokinetics of IFX at induction on treatment
failure. METHODS: This is a longitudinal cohort study on 269 patients with IBD
treated with IFX in a single center. A total of 2331 blood samples were
prospectively collected from 2007 until March 2015 with a retrospective analysis
of clinical data. IFX trough levels (TLs) were measured by enzyme-linked
immunosorbent assay. Antibodies to IFX were measured by drug-sensitive bridging
assay. RESULTS: During follow-up, patients were defined according to treatment
outcome. At week 6, median IFX TL in patients requiring a switch to another
treatment due to LOR (LOR switched group) (2.32 MUg/mL [0.12-19.93 MUg/mL]) was
lower than in patients with long-term response (long-term responders) (8.66
MUg/mL [0.12-12.09 MUg/mL], P = 0.007) and in patients responding to optimization
(LOR optimized group) (7.28 MUg/mL [0.17-14.91 MUg/mL], P = 0.021). At week 2,
median IFX TL was lower in the LOR switched group (5.7 MUg/mL [0.15-12.09
MUg/mL]) compared with the long-term responders (11.92 MUg/mL [0.14-19.93
MUg/mL], P = 0.041) but no significant difference was reached with the LOR
optimized group (11.91 MUg/mL [0.23-12.09 MUg/mL], P = 0.065). In the LOR
switched group, median IFX TL at induction (weeks 2 and 6) was significantly
lower when patients had been previously exposed to anti-tumor necrosis factor
compared with naive patients (0.91 MUg/mL [0.12-4.4 MUg/mL] versus 6.6 MUg/mL
[0.15-19.93 MUg/mL], P = 0.044). CONCLUSIONS: This study suggests that patients
who do not respond to any optimization strategy have lower IFX TLs during
induction at week 6. IFX TLs measured early on at induction might predict
treatment failure to IFX during maintenance.
PMID- 28498154
TI - Pediatric-to-adult Transition and Medication Adherence in Patients with
Inflammatory Bowel Disease.
AB - BACKGROUND: Medication nonadherence is common in inflammatory bowel disease and
is associated with poor outcomes. There has been no study on pediatric-to-adult
transition as a risk factor for nonadherence in inflammatory bowel disease, which
has been demonstrated in other diseases. We aimed to assess whether transitioned
(TR) patients have higher nonadherence rates than young adults (YAs) diagnosed in
adulthood. METHODS: Consecutive ambulatory subjects were prospectively recruited
and completed the validated Medication Adherence Reporting Scale (MARS), with the
primary outcome being adherence differences between group age-matched TR and YA
groups. Pediatric subjects were taken as the control group. Perceptions of
medication-related necessity and concerns were assessed with the Beliefs about
Medicines Questionnaire (BMQ). Nonadherers (defined as MARS <=16) received the
Inflammatory Bowel Diseases Pharmacist Adherence Counselling (IPAC) intervention
and adherence change was reassessed after 6 months as a secondary outcome.
RESULTS: Adherence in TR patients (n = 38, mean age 20.4, 13.2% nonadherent) was
noninferior to and numerically better than YAs diagnosed in adulthood (n = 41,
mean age 21.2, 24.4%). Nonadherence in the pediatric control group (n = 50, mean
age 14.7) was 8.0%. YAs had significantly higher medication-related concerns
(14.6 versus 11.9, P = 0.02) than the pediatric group. The IPAC intervention
reduced nonadherence rates by 60% (P = 0.004). CONCLUSIONS: TR patients did not
have worse adherence than YAs diagnosed in adulthood. Protective factors may
include previous treatment in pediatric centers and the salient symptomatology of
inflammatory bowel disease, whereas increasing concerns over medications
contribute to nonadherence in YAs. Pharmacist-led counselling improves adherence
in these patients.
PMID- 28498155
TI - Therapeutic Drug Monitoring to Guide Infliximab Dose Adjustment is Associated
with Better Endoscopic Outcomes than Clinical Decision Making Alone in Active
Inflammatory Bowel Disease.
AB - BACKGROUND: Adequate infliximab (IFX) levels are associated with favorable
outcomes in inflammatory bowel disease. Using therapeutic drug monitoring (TDM)
to guide dosing is cost effective and associated with clinical improvement, but
effect on endoscopic outcomes remains unclear. METHODS: Primary responders to IFX
who underwent dose escalation (2008-2014) were reviewed. Patients with active
endoscopic disease were included. Two cohorts were examined: TDM-based decision
to escalate (TDM) and clinical decision (non-TDM). Outcomes recorded at median 6
months after adjustment included endoscopic remission (Mayo <1, Simple Endoscopic
Score for Crohn's Disease <3), C-reactive protein, and inflammatory bowel disease
specific health care utilization. Postadjustment IFX and antibodies to infliximab
levels discriminant for endoscopic remission were determined. Multivariable
regression evaluated independent predictors of remission. RESULTS: Of note, 312
dose optimizations were examined (149 TDM and 163 non-TDM). Clinically, groups
were similar. Sixty-three percent TDM attained postadjustment endoscopic
remission compared with 48% non-TDM (P < 0.05). Sixty-nine percentage TDM had
significant clinical response (57% non-TDM [P < 0.01]); fewer were hospitalized
(22% TDM versus 35% non-TDM, P = 0.025). Patients with ulcerative colitis had
shorter time to escalation (10 versus 20 mo, P < 0.0001). Median IFX levels
increased after escalation in TDM (1.5 [pre] and 11 MUg/mL [post]; P < 0.0001)
and were higher than non-TDM postadjustment levels (11 versus 6.5 MUg/mL, P =
0.015). Postadjustment IFX >4.5 MUg/mL (area under curve = 0.8; 95% confidence
interval, 0.71-0.88) and antibodies to infliximab <3.3 U/mL (area under curve =
0.70; 95% confidence interval, 0.63-0.81) were associated with endoscopic
remission. Multivariable analysis showed that IFX concentration (odds ratio 1.2
[95% confidence interval, 1.1-1.3]; P < 0.0001) remained an independent predictor
of endoscopic remission. CONCLUSIONS: TDM before dose adjustment is associated
with higher postadjustment levels and endoscopic remission.
PMID- 28498156
TI - Coping with Inflammatory Bowel Disease: Engaging with Information to Inform
Health-Related Decision Making in Daily Life.
AB - BACKGROUND: People with inflammatory bowel disease (IBD) require disease and
lifestyle information to make health-related decisions in their daily lives.
Derived from a larger qualitative study of the lived experiences of people with
IBD, we report on findings that explored how people with IBD engage with health
related information in their daily lives. METHODS: Participants were recruited
primarily from the Manitoba IBD Cohort Study. We used purposive sampling to
select people with a breadth of characteristics and experiences. Individual
interviews were audio-recorded and transcribed verbatim. Data were analyzed using
inductive qualitative methods consistent with a phenomenological approach.
RESULTS: Forty-five people with IBD participated; 51% were women. Findings
highlighted the temporal and contextual influences on engagement with health
related information. Temporal influences were described as the changing need for
health-related information over time. Participants identified 6 contextual
factors influencing engagement with information to make health decisions: (1)
emotional and attitudinal responses, (2) perceived benefits and risks, (3) trust
in the source of the information, (4) knowledge and skills to access and use
information, (5) availability of evidence to support decisions, and (6) social
and economic environments. CONCLUSIONS: Findings illustrate the changing needs
for health-related information over the course of IBD, and with evolving health
and life circumstances. Practitioners can be responsive to information needs of
people with IBD by having high-quality information available at the right time in
a variety of formats and by supporting the incorporation of information in daily
life.
PMID- 28498157
TI - Compositional Changes in the Gut Mucus Microbiota Precede the Onset of Colitis
Induced Inflammation.
AB - BACKGROUND: Inflammatory bowel disease (IBD) is associated with an inappropriate
immune response to the gut microbiota. Notably, patients with IBD reportedly have
alterations in fecal microbiota. However, the colonic microbiota occupies both
the gut lumen and the mucus covering the epithelium. Thus, information about
mucus-resident microbiota fails to be conveyed in the routine microbiota analyses
of stool samples. Further, studies analyzing microbiota in IBD have mainly
focused on stool samples taken after onset of inflammation. Our objective was to
investigate both temporal and spatial changes in colonic microbiota communities
preceding the onset of colitis. METHODS: We studied mucus and stool microbiota
using a spontaneous model of colitis, the mdr1a mouse, and their respective wild
type littermate controls in a time series mode. RESULTS: Using this approach we
have shown that microbial dysbiosis was evident in the mucus but not stools, with
reduced abundance of Clostridiales evident in the mucus but not stools, of
colitis-prone mice mdr1a mice 12 weeks before the onset of detectable
inflammation. This altered microbial composition was coupled with a significantly
thinner mucus layer. On emergence of inflammation, dysbiosis was evident in the
stools and at this time point, the spatial segregation between microbiota and
host tissue was also disrupted, correlating with worsened inflammation. Our
results reveal that microbial dysbiosis is detectable before changes in the
stools. Importantly, dysbiosis in the mucus layer preceded development of
colitis. CONCLUSIONS: Our data reveal the importance of mucus sampling for
understanding the underlying etiology of IBD and fundamental processes underlying
disease progression.
PMID- 28498158
TI - Transmural Healing Is Associated with Improved Long-term Outcomes of Patients
with Crohn's Disease.
AB - BACKGROUND: Mucosal healing (MH) is currently accepted as one of the best
treatment targets in Crohn's disease. However, even in patients with sustained
MH, residual bowel wall inflammation can still be detected by cross-sectional
imaging. The long-term benefits of obtaining transmural healing (TH) have not
been previously assessed. METHODS: We performed an observational study including
214 patients with Crohn's disease with a magnetic resonance enterography (MRE)
and colonoscopy performed within a 6-month interval. Patients were classified as
having TH (inactive MRE and colonoscopy), MH (active MRE with inactive
colonoscopy), or no healing (active colonoscopy). Need for surgery, hospital
admission, and therapy escalation were evaluated at 12 months of follow-up.
RESULTS: Patients with TH presented lower rates of hospital admission, therapy
escalation, and surgery than patients with MH or no healing. In logistic
regression analysis, endoscopic remission (odds ratio 0.331 95% confidence
interval [0.178-0.614], P < 0.001) and MRE remission (odds ratio 0.270 95%
confidence interval [0.130-0.564], P < 0.001) were independently associated with
a lower likelihood of reaching any unfavorable outcome. CONCLUSIONS: TH is
associated with improved long-term outcomes in Crohn's disease and may be a more
suitable target than MH.
PMID- 28498160
TI - Not all measurement instruments are created equal.
PMID- 28498159
TI - Fecal Calprotectin Is Not Affected by Pregnancy: Clinical Implications for the
Management of Pregnant Patients with Inflammatory Bowel Disease.
AB - BACKGROUND: Noninvasive biomarkers of inflammation for monitoring inflammatory
bowel disease (IBD) are important in pregnancy. Clinical and laboratory markers
are often affected by the physiological adaption that occurs during pregnancy,
although, few, if any, data exist on fecal calprotectin (FC). We investigated FC
concentrations in pregnant controls and IBD women, and whether FC correlated with
physician global assessment (PGA), C-reactive protein (CRP), and Harvey-Bradshaw
Index (HBI)/Simple Clinical Colitis Activity Index (SCCAI) before and after
pregnancy, as well as during each trimester. METHODS: The study is a prospective
multicenter study of 46 pregnant women with and 21 without IBD in Denmark,
Australia, and New Zealand. Demographics, clinical parameters, and HBI/SCCAI were
recorded. Stool and blood samples were obtained to determine FC and CRP
concentrations. RESULTS: From pregnant IBD women and pregnant controls, 174 and
21 fecal samples were collected, respectively. The median FC concentration in
pregnant IBD women was 131 MUg/g (range 0-3600) and in controls 0 MUg/g (range 0
84) (P < 0.0001). FC strongly correlated with PGA at all 5 timepoints (r >= 0.80;
P < 0.0001) and with HBI/SCCAI before (r = 0.66; P < 0.0001) and after pregnancy
(r = 0.47; P < 0.003) but not during pregnancy (P > 0.05). An FC cutoff
concentration of 250 MUg/g significantly correlated with active disease according
to PGA in all 5 periods (P <= 0.0002). CRP only significantly correlated with FC
(P = 0.0007) and PGA in the second trimester (P = 0.0003). No significant
correlation was found between CRP and HBI/SCCAI at any timepoint (P > 0.05).
CONCLUSIONS: The physiological changes that occur during pregnancy do not affect
FC, in contrast to CRP and HBI/SCCAI. The combined use of FC and PGA seems
optimal to assess disease activity in IBD during pregnancy.
PMID- 28498161
TI - Pediatric tonsillectomy quality of life assessment instruments: a scoping review
protocol.
AB - REVIEW QUESTION/OBJECTIVE: The objective of this scoping review is to investigate
quality of life (QoL) questionnaires available to pediatric patients following
tonsillectomies with or without adenoidectomies for chronic infection or sleep
disordered breathing (SDB). The scoping review will aim to map the components of
each QoL questionnaire assessed including frequency of use, age parameters,
respondent, domains assessed, format and psychometric properties. Questionnaire
format will be summarized into respondent and administrator burden by identifying
the number of questions present, scale utilized and time to completion. The
scoping review will report on whether psychometric analysis in terms of test
reliability and validity was assessed in the included papers as well as the
results of those assessments.Specifically, the review question is: what QoL
questionnaires are available for pediatric patients following tonsillectomies
with or without adenoidectomies for chronic infections or SDB?
PMID- 28498162
TI - Effectiveness of psychosocial interventions on the psychological health and
wellbeing of family carers of people with dementia following residential care
placement: a systematic review protocol.
AB - REVIEW QUESTION/OBJECTIVE: The objective of this review is to identify, appraise
and synthesize existing evidence regarding the effectiveness of psychosocial
interventions on the psychological health and emotional wellbeing of family
carers of people with dementia who have moved into residential care.More
specifically, the objectives are to determine the effectiveness of psychosocial
interventions on any of these family carer outcomes after placement in
residential care: burden, anxiety, stress, depression, guilt, grief and loss,
quality of life and satisfaction with the care of the person with dementia.
PMID- 28498163
TI - Oral hygiene in patients with chronic obstructive pulmonary disease: a scoping
review protocol.
AB - SCOPING REVIEW OBJECTIVE: It is hypothesized that systematic oral hygiene may
reduce airway infections in patients with chronic obstructive pulmonary disease
(COPD). Before considering doing a systematic review, a scoping review is
necessary to explore and map literature on the subject and identify which
interventions have been carried out, if there is relevant literature available
for a systematic review, or if further research should be initiated.The objective
of this scoping review is to comprehensively identify and describe qualitative or
quantitative literature reporting of non-invasive interventions that have been
carried out to improve oral hygiene and relieve and/or reduce respiratory tract
infections, exacerbation and/or hospital readmission in patients with diagnosed
with COPD. A further objective is to undertake a comprehensive search to identify
qualitative literature reporting on the experiences of oral hygiene in people
diagnosed with COPD and/or their relatives and/or healthcare providers
(HCPs).Specifically, the scoping review questions are as follows.
PMID- 28498164
TI - Functional status and physical impairments of adult patients infected with the
human immunodeficiency virus admitted to hospital: a scoping review protocol.
AB - RESEARCH QUESTION/OBJECTIVE: The objectives of this scoping review are to
describe the physical impairments and subsequent level of function of adult
individuals infected with the human immunodeficiency virus (HIV) admitted to an
acute care hospital, determine the outcome measures used by rehabilitation
professionals when evaluating said impairments and level of function in the
population of interest, and identify the rehabilitation interventions offered to
individuals while in hospital as a means of addressing these physical impairments
and individuals' functional status.Specifically, the research questions are:The
current scoping review will comprehensively identify the physical impairments of
people living with HIV when admitted to an acute care hospital and highlight the
subsequent influence on their level of function as a means of emphasizing the
disability present. Findings regarding the rehabilitation interventions offered
could inform clinical practice as a means of mapping which interventions are
offered to address the related physical impairments and thus highlight areas for
future research.
PMID- 28498165
TI - Experiences of the home-dwelling elderly in the use of telecare in home care
services: a qualitative systematic review protocol.
AB - REVIEW QUESTION/OBJECTIVE: The objective of this systematic review is to identify
and synthesize the best evidence on the home-dwelling elderly's experiences with
the use of telecare in home care services. Furthermore, the study will identify
experiences with telecare devices and examine what beliefs the home-dwelling
elderly hold regarding the impact of telecare on the ability to age in
place.Review question 1: How do the home-dwelling elderly experience the use of
telecare in the context of home care services?Review question 2: How do the home
dwelling elderly experience telecare devices?Review question 3: What beliefs do
the home-dwelling elderly hold regarding the impact of telecare on the ability to
age in place?
PMID- 28498166
TI - Effectiveness of telehealth on correctional facility health care: a systematic
review protocol.
AB - REVIEW QUESTION/OBJECTIVE: The objective of this review is to identify the
effectiveness of telehealth in improving correctional facility health care. The
outcomes of the review will include the primary outcomes of access to health care
and costs associated with health care and the secondary outcome of virologic
suppression.Specifically, the review question is: What is the effect of
telehealth compared to usual care on improving correctional facility health care
and decreasing costs in correctional facility health care?
PMID- 28498167
TI - New midwives' experiences of transition support during their first year of
practice: a qualitative systematic review protocol.
AB - REVIEW QUESTION/OBJECTIVE: The current review aims to investigate new midwives'
experiences of transition support during their first year of practice as
registered midwives. A further objective is to identify the social support
experiences of new midwives during their first year of practice as registered
midwives.Specifically, the review question is: How do new graduate midwives
experience transition and social support during their first year of practice?
PMID- 28498168
TI - Effectiveness of formal hand hygiene education and feedback on healthcare
workers' hand hygiene compliance and hospital-associated infections in adult
intensive care units: a systematic review protocol.
AB - REVIEW QUESTION/OBJECTIVE: The objective of this quantitative systematic review
is to identify and synthesize evidence on the effectiveness of formal hand
hygiene education with and without feedback on healthcare workers' hand hygiene
compliance and healthcare-associated infections in adult intensive care units.
PMID- 28498169
TI - Experiences and expectations of return-to-work programs for nurses and midwives
who have acquired a musculoskeletal disorder in the workplace: a qualitative
systemic review protocol.
AB - REVIEW QUESTION/OBJECTIVE: The objective of this systematic review is to identify
and synthesize the best available evidence on the experiences and expectations of
being involved in a program that aims to return nurses and midwives, who have
acquired a musculoskeletal disorder (MSD) in the workplace, to work.The specific
review questions are.
PMID- 28498170
TI - Coping with Parkinson's disease in everyday life: a systematic review protocol.
AB - REVIEW QUESTION/OBJECTIVE: The purpose of this systematic review is to synthesize
the best available qualitative evidence on how individuals with Parkinson's
disease cope with the disease in daily life.
PMID- 28498171
TI - Experiences of unpaid family/friend caregivers of community-dwelling adults with
dementia: a systematic review protocol.
AB - REVIEW QUESTION/OBJECTIVE: The objective of the review is to synthesize evidence
regarding the experiences of unpaid caregivers of community-dwelling adults with
dementia. Specifically, the review question is: What are the experiences and
perceptions of unpaid caregivers providing care for community-dwelling adults
with dementia?
PMID- 28498172
TI - Effectiveness of Patient Safety Leadership WalkRoundsTM on patient safety
culture: a systematic review protocol.
AB - REVIEW QUESTION/OBJECTIVE: The review objective is to synthesize the effect of
Patient Safety Leadership WalkRounds (PSLWs) on patient safety culture
(PSC).Specifically, the review question is: What is the effect of PSLWs on the
PSC in hospitals, measured with validated surveys?
PMID- 28498173
TI - The meaning of confidence for older people living with frailty: a qualitative
systematic review.
AB - BACKGROUND: In many countries, the oldest old (those aged 85 years and older) are
now the fastest growing proportion of the total population. This oldest
population will increasingly be living with the clinical condition of frailty.
Frailty syndromes negatively impact on the person as they do the healthcare
systems supporting them. Within healthcare literature "loss of confidence" is
occasionally connected to older people living with frailty, but ambiguously
described. Understanding the concept of confidence within the context of frailty
could inform interventions to meet this growing challenge. OBJECTIVES: The
objective of this systematic review was to explore the meaning of confidence from
the perspective of older people living with frailty through synthesis of
qualitative evidence to inform healthcare practice, research and policy.
INCLUSION CRITERIA TYPES OF PARTICIPANTS: Studies that included frail adults,
aged over 60 years, experiencing acute hospital and or post-acute care in the
last 12 months. PHENOMENA OF INTEREST: The concept of "confidence" and its impact
on the physical health and mental well-being of older people living with frailty.
CONTEXT: Studies that reported on the older person's descriptions, understanding
and meaning of confidence in relation to their frailty or recent healthcare
experiences. TYPES OF STUDIES: Studies of qualitative design and method. SEARCH
STRATEGY: A three step search strategy was used. The search strategy explored
published studies and gray literature. Publications in English from the last 20
years were considered for inclusion. METHODOLOGICAL QUALITY: All included
articles were assessed by two independent reviewers using the Joanna Briggs
Institute Qualitative Assessment Review Instrument (JBI-QARI). DATA EXTRACTION:
Data were extracted from included studies using the data extraction tools
developed by the Joanna Briggs Institute. DATA SYNTHESIS: Qualitative research
findings were collated using a meta-aggregative approach and JBI-QARI software.
RESULTS: Synthesized findings of this review were drawn from just four research
studies that met the inclusion criteria. Only six findings contributed to the
creation of three categories. These informed a single synthesized finding:
Vulnerability, described as a fragile state of well-being that is exposed to the
conflicting tensions between physical, emotional and social factors. These
tensions have the capability to enhance or erode this state. CONCLUSIONS:
Assertions that an understanding of the concept confidence has been reached
cannot be made. The review data offer limited insight into the concept of
confidence being described by the cohort of older people living with frailty.
PMID- 28498174
TI - Adult women's experiences of urinary incontinence: a systematic review of
qualitative evidence.
AB - BACKGROUND: Women are affected dramatically by urinary incontinence (UI). This
disease is currently considered as epidemic. OBJECTIVE: The objective of this
review is to identify, through the best available evidence, how women experience
UI worldwide. INCLUSION CRITERIA TYPES OF PARTICIPANTS: The current review
included studies of adult women who had experienced UI. PHENOMENA OF INTEREST:
Women with UI from various social and cultural settings were included in this
review. TYPES OF STUDIES: Qualitative data including, but not limited to, study
designs such as phenomenology, grounded theory, ethnography, action research and
feminist research were included in this review. OUTCOMES: All aspects related to
the experience of UI endured by women were considered. SEARCH STRATEGY: An
initial search of MEDLINE (PubMed) and CINAHL was done, followed by the
exploration of all the databases and all identified studies, published in
English, Spanish, French and Portuguese. The databases searched were CINAHL,
PubMed, PsycINFO, Lilacs, Scielo, BVS, BVS-Psi, Scopus, Embase, Sociological
Abstracts, Dissertation Abstracts International and the University of Sao Paulo
Dissertations and Thesis bank and gray literature. METHODOLOGICAL QUALITY: Each
primary study was assessed by two independent reviewers for methodological
quality. The Joanna Briggs Institute Qualitative Appraisal and Review Instrument
(JBI-QARI) data extraction form for interpretive and critical research was used
to appraise the methodological quality of all papers. DATA EXTRACTION:
Qualitative data were extracted using the JBI-QARI. DATA SYNTHESIS: Qualitative
research findings were synthesized using the JBI-QARI. RESULTS: From the 28
studies were included, 189 findings were extracted and they were grouped into 25
categories and eight synthesized findings: (i) cultural and religious backgrounds
and personal reluctance contribute to delays in seeking UI treatment; (ii) the
inevitable and regrettable problem of UI endured silently and alone affects
women's daily activities and their social roles; (iii) poor knowledge and the
vague nature of the symptoms mask the fact that UI is a disease; (iv) the
experiences provoked by UI and the sense of shame regarding the condition have
contributed to impair women's lives; (v) UI has provoked negative effects on
women's intimacy and sexual satisfaction and provoked changes in the ways they
experience their sexuality and sexual function; (vi) UI is considered a
consequence of pregnancy and childbirth, inherent to aging or a religious
punishment; (vii) the women affected by UI adopt several strategies to improve
their health status; and (viii) women have personal preferences toward care
providers and treatments; they confront difficulties through UI treatment and
some care needs are not met. CONCLUSION: Personal and tailored health care should
be provided, and preferences and expectations should be taken into consideration
in the provision of health care to the people affected by UI.
PMID- 28498175
TI - Experiences of healthcare professionals of having their significant other
admitted to an acute care facility: a qualitative systematic review.
AB - BACKGROUND: Most healthcare professionals at some time will experience having a
significant other admitted to an acute care hospital. The knowledge and
understanding that these individuals possess because of their professional
practice can potentially alter this experience. Expectations of staff and other
family members (FMs) can potentially increase the burden on these health
professionals. All FMs of patients should have their needs and expectations
considered; however, this review specifically addresses what may be unique for
healthcare professionals. OBJECTIVES: To synthesize the qualitative evidence on
the experiences of healthcare professionals when their significant others are
admitted to an acute care hospital. INCLUSION CRITERIA TYPES OF PARTICIPANTS: The
current review considered studies reporting the experiences of healthcare
professionals, specifically registered nurses (RNs) and physicians. PHENOMENA OF
INTEREST: The experiences of RNs and physicians when a significant other is
admitted to an acute care facility. TYPES OF STUDIES: Qualitative studies that
have examined the phenomenon of interest including, but not limited to, designs
such as phenomenology and grounded theory. SEARCH STRATEGY: The search strategy
aimed to find both published and unpublished studies with no date restrictions.
Only studies published in English were considered for inclusion in this review.
METHODOLOGICAL QUALITY: Qualitative papers selected for retrieval were assessed
using the standardized critical appraisal instrument from the Joanna Briggs
Institute Qualitative Assessment and Review Instrument (JBI-QARI). DATA
EXTRACTION: Data were extracted from the seven included papers using the
standardized data extraction tool from JBI-QARI. DATA SYNTHESIS: The data were
synthesized using the JBI approach to meta-synthesis by meta-aggregation using
the JBI-QARI software and methods. RESULTS: Seven studies of moderate quality
were included in the review. Forty findings were extracted and aggregated to
create 10 categories, from which five synthesized findings were derived:
CONCLUSION: In contrast to "lay" FMs, health professionals possess additional
knowledge and understanding that alter their perceptions and expectations, and
the expectations others have of them. This knowledge and understanding can be an
advantage in navigating a complex health system but may also result in an
additional burden such as role conflict.
PMID- 28498176
TI - Effectiveness of haloperidol prophylaxis in critically ill patients with a high
risk of delirium: a systematic review.
AB - BACKGROUND: Delirium is associated with increased intensive care unit and
hospital length of stay, prolonged duration of mechanical ventilation, unplanned
removal of tubes and catheters, and increased morbidity and mortality.
Prophylactic treatment with low-dose haloperidol may have beneficial effects for
critically ill patients with a high risk of delirium. OBJECTIVES: To identify the
effectiveness of haloperidol prophylaxis in critically ill patients with a high
risk for delirium. INCLUSION CRITERIA TYPES OF PARTICIPANTS: Patients with a
predicted high risk of delirium, aged 18 years or over, and in intensive care
units. Patients with a history of concurrent antipsychotic medication use were
excluded. TYPES OF INTERVENTION(S)/PHENOMENA OF INTEREST: Haloperidol prophylaxis
for preventing delirium. TYPES OF STUDIES: Experimental and epidemiological study
designs. OUTCOMES: Primary outcome is the incidence of delirium. Secondary
outcomes are duration of mechanical ventilation, incidence of re-intubation,
incidence of unplanned/accidental removal of tubes/lines and catheters, intensive
care unit and hospital length of stay, and re-admissions to both settings. SEARCH
STRATEGY: An initial search of MEDLINE and CINAHL was undertaken, followed by a
second search for published and unpublished studies from January 1967 to
September 2015 in major healthcare-related electronic databases. Studies in
English, Spanish and Portuguese were included. METHODOLOGICAL QUALITY: Two
independent reviewers assessed the methodological quality of five studies using
the standardized critical appraisal instrument from the Joanna Briggs Institute
Meta-Analysis of Statistics Assessment and Review Instrument. There was general
agreement among the reviewers to exclude one relevant study due to methodological
quality. DATA EXTRACTION: Data were extracted using the JBI data extraction form
for experimental studies and included details about the interventions,
populations, study methods and outcomes of significance to the review questions.
DATA SYNTHESIS: Significant differences were found between participants,
interventions, outcome measures (clinical heterogeneity) and designs
(methodological heterogeneity). For these reasons, we were unable to perform a
meta-analysis. Therefore, the results have been described in a narrative format.
RESULTS: Five studies met the inclusion criteria. One of these studies was
excluded due to poor methodological quality. The remaining four original studies
(total of 1142 patients) were included in this review. Three studies were
randomized controlled trials and one was a cohort study.Two studies confirmed the
effectiveness of haloperidol prophylaxis in critically ill patients with a high
risk of delirium. These studies showed that short-term prophylactic
administration of low-dose intravenous haloperidol significantly decreased the
incidence of delirium in elderly patients admitted to intensive care units after
non-cardiac surgery and in general intensive care unit patients with a high risk
of delirium.However, the two remaining studies showed contradictory results in
mechanically ventilated critically ill adults, revealing that the administration
of haloperidol reduced delirium prevalence, delayed its occurrence, and/or
shorten its duration. CONCLUSIONS: The evidence related to the effectiveness of
haloperidol prophylaxis in critically ill patients with a high risk of delirium
is contradictory. However, balancing the benefits and low side effects associated
with haloperidol prophylaxis, this preventive intervention may be useful to
reduce the incidence of delirium in critically ill adults in intensive care
units.
PMID- 28498177
TI - Effectiveness of topical skin products in the treatment and prevention of
incontinence-associated dermatitis: a systematic review.
AB - BACKGROUND: Incontinence-associated dermatitis (IAD) is inflammation of the skin
resulting from repeated contact with urine and/or feces. It causes pain, redness,
swelling and excoriation, and may lead to complications such as fungal skin
infections and pressure injuries. It is important to prevent and treat IAD to
avoid complications and improve patient outcomes. A number of products are
available for protecting skin, but evidence on their effectiveness is limited.
OBJECTIVES: The current review aimed to establish the effectiveness of topical
skin products in reducing the occurrence and/or severity of IAD. INCLUSION
CRITERIA TYPES OF PARTICIPANTS: Adult patients over the age of 18 years with
incontinence and/or diarrhea. TYPES OF INTERVENTION: Topical skin products as
individual interventions or part of a skin care regimen. TYPES OF STUDIES: Both
published and unpublished study designs including randomized controlled trials,
non-randomized controlled trials, quasi-experimental, before and after,
prospective and retrospective cohort, case-control, analytical cross-sectional,
descriptive study designs including case series, individual case reports and
descriptive cross-sectional studies across all care settings for inclusion.
OUTCOMES: The primary outcome of interest was the absence or non-development,
reduction or resolution, new development or increase in the occurrence of IAD or
the increase in severity of IAD. The secondary outcome was any adverse effect
caused by the skin care products used. SEARCH STRATEGY: A three-step search
strategy to find both published and unpublished papers was utilized in this
review. Studies were limited to those published in English from 1980 to 2016.
METHODOLOGICAL QUALITY: Papers selected were assessed by two independent
reviewers using the Joanna Briggs Institute Meta-Analysis of Statistics
Assessment and Review Instrument (JBI-MAStARI). DATA EXTRACTION: Data were
extracted using the standardized data extraction tool in JBI-MAStARI. The data
extracted included specific details about the interventions, populations, study
methods and outcomes. DATA SYNTHESIS: Studies were assessed for methodological
quality and statistical significance to determine validity and generalizability
of study results. It was not possible to pool studies to conduct meta-analysis or
test for heterogeneity. RESULTS: There were a limited number of clinical trials
that compared products for efficacy in preventing and treating IAD. Assessment
tools and severity scores used to measure skin damage outcomes were dissimilar
and prone to subjectivity. It was difficult to ascertain superiority of any
individual product. CONCLUSION: Information on barrier protective efficacy, side
effects and cost can be valuable to both clinicians and care providers. More
randomized controlled trials on product effectiveness for prevention and
treatment of IAD are highly recommended.
PMID- 28498178
TI - Supporting Implementation Research to Improve Coverage and Uptake of HIV Related
Interventions.
AB - In 2015, Global Affairs Canada joined other members of the United Nations to
establish the Sustainable Development Goals, which include the elimination of
AIDS by 2030. Innovation is an important part of accelerating the response
against HIV and ensuring success in eliminating AIDS by 2030. This is the reason
Global Affairs Canada decided to partner with the World Health Organization, to
support the INtegration and Scaling Up PMTCT through Implementation REsearch
(INSPIRE) initiative, to learn how HIV interventions can be successfully
integrated with other essential health services for mothers and children,
especially among the most vulnerable populations. Canada also believes that the
empowerment of women and girls will be critical to eliminating AIDS. INSPIRE is
the evidence that providing women with the knowledge and skills necessary to
prevent, treat, and manage HIV enables them to become experts and agents of
change in their families and communities. We know that when women are empowered
with critical information regarding their health, there is greater retention in
care which leads to improved treatment adherence and ultimately helps to reduce
the rate of new infections. Global Affairs Canada is proud to have supported the
World Health Organization in this effort.
PMID- 28498179
TI - Improving Retention in Care Among Pregnant Women and Mothers Living With HIV:
Lessons From INSPIRE and Implications for Future WHO Guidance and Monitoring.
AB - Identifying women living with HIV, initiating them on lifelong antiretroviral
treatment (ART), and retaining them in care are among the important challenges
facing this generation of health care managers and public health researchers.
Implementation research attempts to solve a wide range of implementation problems
by trying to understand and work within real-world conditions to find solutions
that have a measureable impact on the outcomes of interest. Implementation
research is distinct from clinical research in many ways yet demands similar
standards of conceptual thinking and discipline to generate robust evidence that
can be, to some extent, generalized to inform policy and service delivery. In
2011, the World Health Organization (WHO), with funding from Global Affairs
Canada, began support to 6 implementation research projects in Malawi, Nigeria,
and Zimbabwe. All focused on evaluating approaches for improving rates of
retention in care among pregnant women and mothers living with HIV and ensuring
their continuation of ART. This reflected the priority given by ministries of
health, program implementers, and researchers in each country to the importance
of women living with HIV returning to health facilities for routine care,
adherence to ART, and improved health outcomes. Five of the studies were cluster
randomized controlled trials, and 1 adopted a matched cohort design. Here, we
summarize some of the main findings and key lessons learned. We also consider
some of the broader implications, remaining knowledge gaps, and how
implementation research is integral to, and essential for, global guideline
development and to inform HIV/AIDS strategies.
PMID- 28498180
TI - Beyond "Option B+": Understanding Antiretroviral Therapy (ART) Adherence,
Retention in Care and Engagement in ART Services Among Pregnant and Postpartum
Women Initiating Therapy in Sub-Saharan Africa.
AB - BACKGROUND: Several studies from sub-Saharan Africa have highlighted significant
challenges in providing antiretroviral therapy (ART) to pregnant and postpartum
women, with specific concerns around maintaining optimal levels of adherence to
ART and/or retaining women in long-term services. However, there are few
conceptual frameworks to help understand nonadherence and nonretention, as well
as the drivers of these, among HIV-infected women, particularly in the postpartum
period. METHODS: This review provides an overview of the key issues involved in
thinking about ART adherence, retention in care and engagement in ART services
among pregnant and postpartum women. RESULTS: The related behaviors of adherence
and retention may be understood as components of effective engagement of patients
in ART services, which share the goal of achieving and maintaining suppressed
maternal viral load on ART. Under this framework, the existing literature
indicates that disengagement from care is widespread among postpartum women, with
strikingly similar data emerging from ART services around the globe and
indications that similar challenges may be encountered by postpartum care
services outside the context of HIV. However, the drivers of disengagement
require further research, and evidence-based intervention strategies are limited.
CONCLUSIONS: The challenges of engaging women in ART services during pregnancy
and the postpartum period seem pervasive, although the determinants of these are
poorly understood. Looking forward, a host of innovative intervention approaches
are needed to help improve women's engagement, and in turn, promote maternal and
child health in the context of HIV.
PMID- 28498181
TI - Impact of Mother-Infant Pair Clinics and Short-Text Messaging Service (SMS)
Reminders on Retention of HIV-Infected Women and HIV-Exposed Infants in eMTCT
Care in Malawi: A Cluster Randomized Trial.
AB - BACKGROUND: Poor retention of mothers and HIV-exposed infants (HEIs) in HIV care
threatens efforts to eliminate pediatric HIV. Novel strategies are required to
address this challenge. We compared 12-month maternal and HEI postpartum
retention in health facilities implementing the following HIV care delivery
models: integrated HIV and maternal, neonatal, and child health services [mother
infant pair (MIP) clinics], MIP clinics plus short-text messaging service (SMS)
reminders to prevent default (MIP + SMS), and standard of care (SOC). METHODS:
From May 2013 to August 2016, a cluster randomized trial was conducted in rural
Malawi, which randomized 30 health facilities to the 3 service delivery models.
HIV+ pregnant women and HEIs were enrolled and followed up to monitor compliance
with prescheduled visits and retention. Log binomial regression, using
generalized estimated equation, was used to assess the impact of the models on
retention. RESULTS: The trial enrolled 461, 493, and 396 HIV+ pregnant women and
386, 399, and 300 HEIs into the MIP, MIP + SMS, and SOC arms, respectively.
Compared with the 12-month maternal retention rate in the SOC arm (22.2%), the
rates were similar in the MIP arm [19.3%, risk ratio (RR): 0.85, 95% confidence
interval (CI): 0.56 to 1.30] and in the MIP + SMS arm (24.9%, RR: 1.08, 95% CI:
0.87 to 1.35). Compared with the 12-month infant retention rate in the SOC arm
(9.8%), the rates were similar in the MIP arm (8.0%, RR: 0.89, 95% CI: 0.31 to
2.58) and in the MIP + SMS arm (19.5%, RR: 1.40, 95% CI: 0.85 to 2.31).
CONCLUSIONS: MIP and MIP + SMS service delivery models were ineffective in
improving maternal and infant retention in rural Malawi.
PMID- 28498182
TI - Integrating HIV and Maternal, Neonatal and Child Health Services in Rural Malawi:
An Evaluation of the Implementation Processes and Challenges.
AB - INTRODUCTION: Introducing Option B+ in Malawi increased antiretroviral therapy
coverage among pregnant and breastfeeding women 3 fold. The Promoting Retention
among Infants and Mothers Effectively (PRIME) study integrated care of Maternal,
Neonatal and Child Health services through a mother-infant pair (MIP) clinic.
This article evaluates the implementation processes and challenges health care
workers' experienced in implementing these MIP clinics. METHODS: Between May 2013
and August 2016, 20 health facilities implemented MIP clinics. Health care
workers' performance implementing MIP clinics was assessed through a mentorship
score from 0 to 5 and supplemented with qualitative data from mentorship reports.
Visit alignment of participants' appointment and attendance dates with MIP clinic
dates were calculated and summarized by overall proportions among all patient
visits. RESULTS: The average mentorship score was 3.8, improving from 3.0 to 4.2
from quarter one 2015 to quarter one 2016. Proportions of maternal and infant
appointment dates that aligned with MIP clinic dates were 47.0% and 5.9%, with
greatest improvement between 2013 and 2015. Proportions of maternal and infant
attendance dates that aligned with MIP clinic dates were 41.7% and 51.2% and
improved over time. DISCUSSION: Despite improvement in staff mentorship scores,
many MIPs were not exposed to integrated HIV and Maternal, Neonatal and Child
Health services offered through MIP clinics primarily because of clinic
scheduling challenges. To improve utilization of integrated MIP clinics, careful
design of a delivery approach is needed that is acceptable to clinic staff,
addresses local realities, and includes appropriate investment and oversight.
PMID- 28498183
TI - Impact of Facility- and Community-Based Peer Support Models on Maternal Uptake
and Retention in Malawi's Option B+ HIV Prevention of Mother-to-Child
Transmission Program: A 3-Arm Cluster Randomized Controlled Trial (PURE Malawi).
AB - BACKGROUND: Many sub-Saharan African countries have adopted Option B+, a
prevention of mother-to-child transmission approach providing HIV-infected
pregnant and lactating women with immediate lifelong antiretroviral therapy. High
maternal attrition has been observed in Option B+. Peer-based support may improve
retention. METHODS: A 3-arm stratified cluster randomized controlled trial was
conducted in Malawi to assess whether facility- and community-based peer support
would improve Option B+ uptake and retention compared with standard of care
(SOC). In SOC, no enhancements were made (control). In facility-based and
community-based models, peers provided patient education, support groups, and
patient tracing. Uptake was defined as attending a second scheduled follow-up
visit. Retention was defined as being alive and in-care at 2 years without
defaulting. Attrition was defined as death, default, or stopping antiretroviral
therapy. Generalized estimating equations were used to estimate risk differences
(RDs) in uptake. Cox proportional hazards regression with shared frailties was
used to estimate hazard of attrition. RESULTS: Twenty-one facilities were
randomized and enrolled 1269 women: 447, 428, and 394 in facilities that
implemented SOC, facility-based, and community-based peer support models,
respectively. Mean age was 27 years. Uptake was higher in facility-based (86%;
RD: 6%, confidence interval [CI]: -3% to 15%) and community-based (90%; RD: 9%,
CI: 1% to 18%) models compared with SOC (81%). At 24 months, retention was higher
in facility-based (80%; RD: 13%, CI: 1% to 26%) and community-based (83%; RD:
16%, CI: 3% to 30%) models compared with SOC (66%). CONCLUSIONS: Facility- and
community-based peer support interventions can benefit maternal uptake and
retention in Option B+.
PMID- 28498184
TI - Viral Suppression and HIV Drug Resistance at 6 Months Among Women in Malawi's
Option B+ Program: Results From the PURE Malawi Study.
AB - BACKGROUND: In 2011, Malawi launched Option B+, a program of universal
antiretroviral therapy (ART) treatment for pregnant and lactating women to
optimize maternal health and prevent pediatric HIV infection. For optimal
outcomes, women need to achieve HIVRNA suppression. We report 6-month HIVRNA
suppression and HIV drug resistance in the PURE study. METHODS: PURE study was a
cluster-randomized controlled trial evaluating 3 strategies for promoting uptake
and retention; arm 1: Standard of Care, arm 2: Facility Peer Support, and arm 3:
Community Peer support. Pregnant and breastfeeding mothers were enrolled and
followed according to Malawi ART guidelines. Dried blood spots for HIVRNA testing
were collected at 6 months. Samples with ART failure (HIVRNA >=1000 copies/ml)
had resistance testing. We calculated odds ratios for ART failure using
generalized estimating equations with a logit link and binomial distribution.
RESULTS: We enrolled 1269 women across 21 sites in Southern and Central Malawi.
Most enrolled while pregnant (86%) and were WHO stage 1 (95%). At 6 months,
950/1269 (75%) were retained; 833/950 (88%) had HIVRNA testing conducted, and
699/833 (84%) were suppressed. Among those with HIVRNA >=1000 copies/ml with
successful amplification (N = 55, 41% of all viral loads > 1000 copies/ml),
confirmed HIV resistance was found in 35% (19/55), primarily to the nonnucleoside
reverse transcriptase inhibitor class of drugs. ART failure was associated with
treatment default but not study arm, age, WHO stage, or breastfeeding status.
CONCLUSIONS: Virologic suppression at 6 months was <90% target, but the observed
confirmed resistance rates suggest that adherence support should be the primary
approach for early failure in option B+.
PMID- 28498185
TI - The Effect of a Continuous Quality Improvement Intervention on Retention-In-Care
at 6 Months Postpartum in a PMTCT Program in Northern Nigeria: Results of a
Cluster Randomized Controlled Study.
AB - BACKGROUND: Retention in care is critical for improving HIV-infected maternal
outcomes and reducing vertical transmission. Health systems' interventions such
as continuous quality improvement (CQI) may support health services to address
factors that affect the delivery of HIV-related care and thereby influence rates
of retention-in-care. METHODOLOGY: We evaluated the effect of a CQI intervention
on retention-in-care at 6 months postpartum of pregnant women and mothers living
with HIV who had been started on lifelong antiretroviral treatment. Thirty-two
health care facilities were randomized to either implement the intervention or
not. We considered women fully retained in care when they attended the 6-month
postpartum visit and did not miss any previous scheduled visit by more than 30
days. RESULTS: Five hundred eleven women living with HIV attending antenatal
clinics at 26 facilities were included in the analysis. Median age at enrolment
was 27 years and gestational age was 20 weeks. Seventy-one percent of women were
seen at 6-month postpartum irrespective of missing any scheduled visit. However,
43% of women were fully retained at 6-month postpartum and did not miss any
scheduled visit based on our stringent study definition of retention. There was
no significant difference in retention at 6 months between the intervention and
control arms [44% vs. 41%, relative risk: 1.08; 95% confidence interval (CI):
0.78 to 1.49]. Initiation of ARV prophylaxis among infants within 72 hours was
not different by study arm (66.0% vs. 74.7%, relative risk = 0.95; 95% CI: 0.84
to 1.07) but rates of early infant testing at 4-6 weeks were higher in
intervention sites (48.8% vs. 25.3%, adjusted relative risk: 1.76; 95% CI: 1.27
to 2.42). CONCLUSIONS: CQI as implemented in this study did not differ across
study arms in the rates of retention. Several intervention design or
implementation issues or other contextual constraints may explain the absence of
effect.
PMID- 28498186
TI - Using Small Tests of Change to Improve PMTCT Services in Northern Nigeria:
Experiences From Implementation of a Continuous Quality Improvement and
Breakthrough Series Program.
AB - BACKGROUND: Continuous Quality Improvement (CQI) is a process where health teams
systematically collect and regularly reflect on local data to inform decisions
and modify local practices and so improve delivery of services. We implemented a
cluster randomized trial to examine the effects of CQI interventions on
Prevention of Mother-to-Child Transmission (PMTCT) services. Here, we report our
experiences and challenges establishing CQI in 2 high HIV prevalence states in
northern Nigeria. METHODS: Facility-based teams were trained to implement CQI
activities, including structured assessments, developing change packages, and
participation in periodic collaborative learning sessions. Locally evolved
solutions (change ideas) were tested and measured using process data and
intermediate process indicators were agreed including overall time spent
accessing services, client satisfaction, and quality of data. RESULTS: Health
workers actively participated in clinic activities and in the collaborative
learning sessions. During the study, the mean difference in time spent accessing
services during clinic visits increased by 40 minutes (SD = 93.4) in the control
arm and decreased by 44 minutes (SD = 73.7) in the intervention arm. No
significant difference was recorded in the mean client satisfaction assessment
score by study arm. The quality of data was assessed using a standardized tool
scored out of 100; compared with baseline data, quality at the end of study had
improved at intervention sites by 6 points (95% CI: 2.0 to 10.1). CONCLUSIONS:
Health workers were receptive to CQI process. A compendium of "change ideas"
compiled into a single change package can be used to improve health care
delivery.
PMID- 28498187
TI - The Impact of Structured Mentor Mother Programs on 6-Month Postpartum Retention
and Viral Suppression among HIV-Positive Women in Rural Nigeria: A Prospective
Paired Cohort Study.
AB - BACKGROUND: Peer support (PS) has reportedly improved Prevention of mother-to
child transmission (PMTCT) outcomes in high HIV-burden settings; however,
evidence of impact on retention in care is limited. Retention in care implies
consistent engagement and treatment adherence. The MoMent study evaluated the
impact of structured vs unstructured PS on postpartum retention and viral load
suppression among rural Nigerian women. METHODS: A total of 497 HIV-positive
pregnant women were consecutively enrolled at 10 primary health care centers with
structured mentor mother (MM) support, and at 10 pair-matched primary health care
centers with routine, ad hoc PS. The structured MM intervention comprised an
outcome-specific scope of work, close MM supervision, standardized documentation,
performance evaluations, and retraining as appropriate. Retention was defined by
clinic attendance during the first 6-month postpartum. Participants with >=3 of 6
expected monthly visits were considered retained. Women with a 6-month postpartum
plasma viral load of <20 copies/mL were considered suppressed. A logistic
regression model with generalized estimating equation was used to assess the
effect of MMs on retention and viral suppression. RESULTS: Exposure to structured
MM support was associated with higher odds of retention than routine PS (adjusted
odds ratio = 5.9, 95% confidence interval: 3.0 to 11.6). Similarly, the odds of
viral suppression at 6-month postpartum were higher for MM-supported women
(adjusted odds ratio = 4.9, 95% confidence interval: 2.6 to 9.2). CONCLUSIONS:
Structured PS significantly improved postpartum PMTCT retention and viral
suppression rates among women in rural Nigeria. Introduction of structure can
enhance the impact of PS interventions on PMTCT outcomes.
PMID- 28498188
TI - The Impact of Structured Mentor Mother Programs on Presentation for Early Infant
Diagnosis Testing in Rural North-Central Nigeria: A Prospective Paired Cohort
Study.
AB - BACKGROUND: Early infant diagnosis (EID) by 2 months of age is an important
prevention of mother-to-child cascade step that serves as an early postpartum
indicator of program success. Uptake and timely presentation for infant HIV
diagnosis are significant challenges in resource-limited settings. Few studies on
maternal peer support (PS) have demonstrated impact on EID. The MoMent study
evaluated the impact of structured PS on timely presentation for EID testing in
rural North-Central Nigeria. METHODS: A total of 497 HIV-positive pregnant women
were consecutively recruited at 10 primary health care centers with structured,
closely supervised Mentor Mother (MM) support, and 10 pair-matched primary health
care centers with routine but ad hoc PS. EID was assessed among HIV-exposed
infants delivered to recruited women, and was defined by presentation for DNA
polymerase chain reaction testing between 35 and 62 days of life. A logistic
regression model with generalized estimating equation to account for clustering
was used to assess the effect of MMs on EID presentation. RESULTS: Data from 408
live-born infants were available for analysis. Exposure to MM support was
associated with higher odds of timely EID presentation among infants, compared
with routine PS (adjusted odds ratios = 3.7, 95% confidence interval: 2.8 to
5.0). CONCLUSIONS: Closely supervised, organized MM support significantly
improved presentation for EID among HIV-exposed infants in a rural Nigerian
setting. Structured PS can improve rates of timely EID presentation and
potentially the uptake of EID testing in resource-limited settings.
PMID- 28498189
TI - Impact of Point-of-Care CD4 Testing on Retention in Care Among HIV-Positive
Pregnant and Breastfeeding Women in the Context of Option B+ in Zimbabwe: A
Cluster Randomized Controlled Trial.
AB - INTRODUCTION: Scale-up of Option B+ in Zimbabwe has increased antiretroviral
therapy (ART) coverage but patient loss-to-follow-up remains high; thus,
effective strategies to improve retention in care are needed. Evidence for
Elimination, a cluster randomized controlled trial, evaluated the impact of point
of-care (POC) CD4 testing with CD4 count-specific adherence counseling on rates
of retention among 1150 HIV-positive pregnant women initiating ART in Zimbabwe.
METHODS: Thirty-two primary care health facilities were randomized to offer
either standard-of-care (SOC) or POC CD4 testing plus CD4-specific counseling to
clients (POC Plus). The primary outcome was the proportion of HIV-positive
pregnant women retained on ART after 12 months, calculated by cluster-adjusted
proportions, unadjusted and adjusted relative risks (RR and aRR, respectively).
RESULTS: Retention in care 12 months after initiation was 50.7% and 54.5% in the
POC Plus and SOC arms, respectively (RR 0.93, 95% confidence interval [CI]: 0.78
to 1.11; aRR 0.91, 95% CI: 0.77 to 1.07). Although considered not retained, 9.7%
transferred to another facility and 0.2% died. Most women, 95.3% in POC Plus and
92.9% in SOC, initiated ART within 1 month of antenatal booking (RR 1.03, 95% CI:
0.97 to 1.08). DISCUSSION: Although patient retention was similar in both arms,
women in the POC Plus arm were more likely to have received a CD4 test at booking
and a repeat CD4 test later in care. CD4 is no longer required for treatment
initiation but is still recommended in national guidelines and is of value in
clinical management. Further work is needed to identify effective strategies to
increase patient retention in ART care.
PMID- 28498190
TI - Patterns of HIV Care Clinic Attendance and Adherence to Antiretroviral Therapy
Among Pregnant and Breastfeeding Women Living With HIV in the Context of Option
B+ in Zimbabwe.
AB - BACKGROUND: Consistent use of antiretroviral therapy (ART) during pregnancy and
breastfeeding reduces the likelihood of mother-to-child HIV transmission. All
pregnant and breastfeeding women living with HIV in Zimbabwe are offered ART with
same-day initiation regardless of CD4 count (Option B+). We investigated patterns
of clinic attendance and adherence to ART among HIV-infected pregnant women in
Zimbabwe. METHODS: The Evidence for Elimination cluster-randomized trial
evaluating point-of-care CD4 testing included 1150 HIV-infected ART-naive women
attending antenatal care between January 2014 and June 2015. Thirty-two primary
care facilities were randomized between 2 arms. In this secondary analysis of
Evidence for Elimination data collected from routine clinic records, we
classified women by number of pills dispensed, and estimated adherence from the
ratio of pills to days since ART initiation (Medication Possession Ratio,
adherent if >=95%) or the period when they stopped receiving medication. RESULTS:
Two-thirds (67.7%) were still receiving medication 1 year after initiation; less
than half of the cohort (39.1%) were adherent. Younger women, newly diagnosed
with HIV, and/or first presenting to antenatal care in their third trimester were
more likely to drop from care or be nonadherent 360 days after ART initiation.
CONCLUSION: Adherence to ART is suboptimal particularly among young, newly
diagnosed, and/or late presenting patients. Interventions that target these
groups, as well as provide additional support to all women who are newly
diagnosed, may improve Option B+ ART care. More information is needed about the
barriers to ART care among late presenters and teenagers.
PMID- 28498191
TI - Impact of Facility-Based Mother Support Groups on Retention in Care and PMTCT
Outcomes in Rural Zimbabwe: The EPAZ Cluster-Randomized Controlled Trial.
AB - BACKGROUND: Prevention of mother-to-child transmission elimination goals are
hampered by low rates of retention in care. The Eliminating Paediatric AIDS in
Zimbabwe project assessed whether mother support groups (MSGs) improve rates of
retention in care of HIV-exposed infants and their HIV-positive mothers, and
maternal and infant outcomes. METHODS: The study involved 27 rural clinics in
eastern Zimbabwe. MSGs were established in 14 randomly selected clinics and met
every 2 weeks coordinated by volunteer HIV-positive mothers. MSG coordinators
provided health education and reminded mothers of MSG meetings by cell phone.
Infant retention in care was defined as "12 months postpartum point attendance"
at health care visits of HIV-exposed infants at 12 months of age. We also
measured regularity of attendance and other program indicators of HIV-positive
mothers and their HIV-exposed infants. RESULTS: Among 507 HIV-positive pregnant
women assessed as eligible, 348 were enrolled and analyzed (69%) with mothers who
had disclosed their HIV status being overrepresented. In the intervention arm,
69% of infants were retained in care at 12 months versus 61% in the control arm,
with no statistically significant difference. Retention and other program
outcomes were systematically higher in the intervention versus control arm,
suggesting trends toward positive health outcomes with exposure to MSGs.
DISCUSSION: We were unable to show that facility-based MSGs improved retention in
care at 12 months among HIV-exposed infants. Selective enrollment of mothers more
likely to be retained-in-care may have contributed to lack of effect. Methods to
increase the impact of MSGs on retention including targeting of high-risk mothers
are discussed.
PMID- 28498192
TI - Patterns of Attendance at Mother Support Groups in Zimbabwe. The EPAZ Trial (2014
2016).
AB - BACKGROUND: In Southern Africa, groups of mothers living with HIV successfully
provide peer psychosocial support during pregnancy and early childhood. We report
patterns of attendance at Mother Support Groups (MSGs) sessions among women and
mothers living with HIV in rural Zimbabwe. METHODS: In the Elimination of
Pediatric AIDS cluster-randomized trial, MSGs were established in 14 health
facilities in Mutare and Makoni districts. Patterns of attendance at MSG sessions
were categorized by calendar attendance from delivery to 6-month postpartum using
a Dynamic Time Warping clustering method. Baseline characteristics of women and
postpartum MSG attendance patterns were described. Linkages between these
patterns and 12-month postpartum retention in care were explored using mixed
effects models. RESULTS: Most women (88%) attended at least 1 MSG session between
enrollment and 6-month postpartum. Two patterns of postpartum MSG attendance,
"Regular Attendance" and "Non-Regular Attendance," were readily identified. Being
older than 32 (P = 0.01), booking for antenatal care before 22 weeks gestational
age (P = 0.02), and being on antiretroviral therapy at first antenatal care
booking (P = 0.01) were significantly associated with "Regular Attendance."
"Regular Attendance" at MSG sessions during the 6-month postpartum period was
significantly associated with better retention in care at 12 months, compared
with "Non-Regular Attendance" (P < 0.01). DISCUSSION: Women living with HIV
attended MSG sessions. However, few attended regularly. Younger and newly
diagnosed women were less likely to attend postpartum MSG sessions or remain in
care at 12 months postpartum. Peer support models should consider specific needs
of these women, especially in rural areas, in order for MSGs to contribute to
improve maternal and child health outcomes.
PMID- 28498193
TI - The Roles of Expert Mothers Engaged in Prevention of Mother-to-Child Transmission
(PMTCT) Programs: A Commentary on the INSPIRE Studies in Malawi, Nigeria, and
Zimbabwe.
AB - INTRODUCTION: Several initiatives aiming to improve retention and adherence in
Prevention of Mother-to-Child Transmission of HIV (PMTCT) programs include
"expert mothers" (EMs) as a central tenet of their interventions. This article
compares the role of EMs in 3 implementation research studies examining
approaches for improving retention in care among mothers living with HIV.
METHODS: We compared and synthesized qualitative data and lessons learned from 3
studies (MoMent in Nigeria, PURE in Malawi, and EPAZ in Zimbabwe) with respect to
the involvement of EMs in supporting PMTCT clients. The frame of reference for
the comparison is the role that EMs play in PMTCT service delivery for
individuals, at the health facility, within the health system, and in the
community. RESULTS: EMs' role was positively perceived by PMTCT clients and
health care workers, as EMs provided an expanded range of services directly
benefiting clients and enabling health care workers to share their workload.
Common challenges included difficulties in reaching male partners and fear of
stigma. The lack of structure and standardization in EM interventions in relation
to eligibility criteria, training, certification, and remuneration were
identified as important barriers to EMs' role development within existing health
systems. CONCLUSIONS: The role of EMs within PMTCT programs continues to expand
rapidly. There is a need for coordinated action to develop shared standards and
principles commensurate with the new roles and additional demands placed on EMs
to support PMTCT services, including EM certification, mentoring and supervision
standards, standardized PMTCT-specific training curricula, and, where
appropriate, agreed remuneration rates.
PMID- 28498194
TI - Modeling the Impact of Retention Interventions on Mother-to-Child Transmission of
HIV: Results From INSPIRE Studies in Malawi, Nigeria, and Zimbabwe.
AB - BACKGROUND: Six implementation research studies in Malawi, Nigeria, and Zimbabwe
tested approaches for improving retention in care among women living with HIV. We
simulated the impact of their interventions on the probability of HIV
transmission during pregnancy and breastfeeding. METHODS: A computer-based state
transition model was developed to estimate the impact of the retention
interventions. Patient-level data from the 6 studies were aggregated and
analyzed, and weighted averages of mother-to-child transmission (MTCT) of HIV
probabilities were presented. The average MTCT probability of the more successful
interventions was applied to national estimates to calculate potential infections
averted if these interventions were taken to scale. RESULTS: Among the total
cohort of 5742 HIV-positive women, almost 80% of all infant infections are
attributed to the roughly 20% of HIV-positive pregnant and breastfeeding women
not retained on antiretroviral therapy. Higher retention in the arms receiving
interventions resulted in an overall lower estimated MTCT probability of 9.9%
compared with 12.3% in the control arms. In the 2 studies that showed a
statistically significant effect, Prevention of MTCT Uptake and Retention (PURE)
and Mother Mentor (MoMent), the difference in transmission rates between
intervention and control arms was 4.1% and 7.3%, respectively. Scaling up
retention interventions nationally in the 3 countries could avert an average of
almost 3000 infant infections annually. CONCLUSIONS: Linking HIV-positive
pregnant women to antiretroviral therapy and retaining them is essential for
addressing the remaining gaps and challenges in HIV/AIDS care and the elimination
of MTCT. At national level, even modest improvements in retention translates into
large numbers of infant infections averted.
PMID- 28498195
TI - Building Health System Capacity Through Implementation Research: Experience of
INSPIRE-A Multi-country PMTCT Implementation Research Project.
AB - BACKGROUND: The INSPIRE-Integrating and Scaling Up PMTCT through Implementation
REsearch-initiative was established as a model partnership of national prevention
of mother-to-child transmission of HIV (PMTCT) implementation research in 3 high
HIV burden countries-Malawi, Nigeria, and Zimbabwe. INSPIRE aimed to link local
research groups with Ministries of Health (MOH), build local research capacity,
and demonstrate that implementation research may contribute to improving health
care delivery and respond to program challenges. METHODOLOGY: We used a mixed
methods approach to review capacity building activities, as experienced by health
care workers, researchers, and trainers conducted in the 6 INSPIRE projects
before and during study implementation. RESULTS: Between 2011 and 2016, over 3400
health care workers, research team members, and community members participated in
INSPIRE activities. This included research prioritization exercises, proposal
development, good clinical practice and research ethics training, data management
and analysis workshops, and manuscript development. Health care workers in
clinics and district health offices acknowledged the value of hosting
implementation research projects and how the quality of services improved.
Research teams acknowledged the opportunities that projects provided for personal
development and the value of participating in a multicountry research network.
DISCUSSION: INSPIRE provided an opportunity for African-led research in which
researchers worked closely with national MOH to identify priority research
questions and implement studies. Close partnerships between research teams and
local implementers facilitated project responsiveness to local program issues.
Consequently, processes and training needed for study implementation also
improved local program management and service delivery. Additional benefits
included improved data management, publications, and career development.
PMID- 28498196
TI - Identifying Increased Risk of Readmission and In-hospital Mortality Using
Hospital Administrative Data: The AHRQ Elixhauser Comorbidity Index.
AB - OBJECTIVE: We extend the literature on comorbidity measurement by developing 2
indices, based on the Elixhauser Comorbidity measures, designed to predict 2
frequently reported health outcomes: in-hospital mortality and 30-day readmission
in administrative data. The Elixhauser measures are commonly used in research as
an adjustment factor to control for severity of illness. DATA SOURCES: We used a
large analysis file built from all-payer hospital administrative data in the
Healthcare Cost and Utilization Project State Inpatient Databases from 18 states
in 2011 and 2012. METHODS: The final models were derived with bootstrapped
replications of backward stepwise logistic regressions on each outcome. Odds
ratios and index weights were generated for each Elixhauser comorbidity to create
a single index score per record for mortality and readmissions. Model validation
was conducted with c-statistics. RESULTS: Our index scores performed as well as
using all 29 Elixhauser comorbidity variables separately. The c-statistic for our
index scores without inclusion of other covariates was 0.777 (95% confidence
interval, 0.776-0.778) for the mortality index and 0.634 (95% confidence
interval, 0.633-0.634) for the readmissions index. The indices were stable across
multiple subsamples defined by demographic characteristics or clinical condition.
The addition of other commonly used covariates (age, sex, expected payer)
improved discrimination modestly. CONCLUSIONS: These indices are effective
methods to incorporate the influence of comorbid conditions in models designed to
assess the risk of in-hospital mortality and readmission using administrative
data with limited clinical information, especially when small samples sizes are
an issue.
PMID- 28498198
TI - Development of a Risk-adjustment Model for the Inpatient Rehabilitation Facility
Discharge Self-care Functional Status Quality Measure.
AB - BACKGROUND: Functional status measures are important patient-centered indicators
of inpatient rehabilitation facility (IRF) quality of care. We developed a risk
adjusted self-care functional status measure for the IRF Quality Reporting
Program. This paper describes the development and performance of the measure's
risk-adjustment model. METHODS: Our sample included IRF Medicare fee-for-service
patients from the Centers for Medicare & Medicaid Services' 2008-2010 Post-Acute
Care Payment Reform Demonstration. Data sources included the Continuity
Assessment Record and Evaluation Item Set, IRF-Patient Assessment Instrument, and
Medicare claims. Self-care scores were based on 7 Continuity Assessment Record
and Evaluation items. The model was developed using discharge self-care score as
the dependent variable, and generalized linear modeling with generalized
estimation equation to account for patient characteristics and clustering within
IRFs. Patient demographics, clinical characteristics at IRF admission, and
clinical characteristics related to the recent hospitalization were tested as
risk adjusters. RESULTS: A total of 4769 patient stays from 38 IRFs were
included. Approximately 57% of the sample was female; 38.4%, 75-84 years; and
31.0%, 65-74 years. The final model, containing 77 risk adjusters, explained
53.7% of variance in discharge self-care scores (P<0.0001). Admission self-care
function was the strongest predictor, followed by admission cognitive function
and IRF primary diagnosis group. The range of expected and observed scores
overlapped very well, with little bias across the range of predicted self-care
functioning. CONCLUSIONS: Our risk-adjustment model demonstrated strong validity
for predicting discharge self-care scores. Although the model needs validation
with national data, it represents an important first step in evaluation of IRF
functional outcomes.
PMID- 28498199
TI - Incorporating Alternative Care Site Characteristics Into Estimates of
Substitutable ED Visits.
AB - BACKGROUND: Several recent efforts to improve health care value have focused on
reducing emergency department (ED) visits that potentially could be treated in
alternative care sites (ie, primary care offices, retail clinics, and urgent care
centers). Estimates of the number of these visits may depend on assumptions
regarding the operating hours and functional capabilities of alternative care
sites. However, methods to account for the variability in these characteristics
have not been developed. OBJECTIVE: To develop methods to incorporate the
variability in alternative care site characteristics into estimates of ED visit
"substitutability." RESEARCH DESIGN, SUBJECTS, AND MEASURES: Our approach uses
the range of hours and capabilities among alternative care sites to estimate
lower and upper bounds of ED visit substitutability. We constructed "basic" and
"extended" criteria that captured the plausible degree of variation in each
site's hours and capabilities. To illustrate our approach, we analyzed data from
22,697 ED visits by adults in the 2011 National Hospital Ambulatory Medical Care
Survey, defining a visit as substitutable if it was treat-and-release and met
both the operating hours and functional capabilities criteria. RESULTS: Use of
the combined basic hours/basic capabilities criteria and extended hours/extended
capabilities generated lower and upper bounds of estimates. Our criteria
classified 5.5%-27.1%, 7.6%-20.4%, and 10.6%-46.0% of visits as substitutable in
primary care offices, retail clinics, and urgent care centers, respectively.
CONCLUSIONS: Alternative care sites vary widely in operating hours and functional
capabilities. Methods such as ours may help incorporate this variability into
estimates of ED visit substitutability.
PMID- 28498197
TI - Overuse of Health Care Services in the Management of Cancer: A Systematic Review.
AB - BACKGROUND: Overuse, the provision of health services for which harms outweigh
the benefits, results in suboptimal patient care and may contribute to the rising
costs of cancer care. We performed a systematic review of the evidence on overuse
in oncology. METHODS: We searched Medline, EMBASE, the Cochrane Library, Web of
Science, SCOPUS databases, and 2 grey literature sources, for articles published
between December 1, 2011 and March 10, 2017. We included publications from
December 2011 to evaluate the literature since the inception of the ABIM
Foundation's Choosing Wisely initiative in 2012. We included original research
articles quantifying overuse of any medical service in patients with a cancer
diagnosis when utilizing an acceptable standard to define care appropriateness,
excluding studies of cancer screening. One of 4 investigator reviewed titles and
abstracts and 2 of 4 reviewed each full-text article and extracted data.
Methodology used PRISMA guidelines. RESULTS: We identified 59 articles measuring
overuse of 154 services related to imaging, procedures, and therapeutics in
cancer management. The majority of studies addressed adult or geriatric patients
(98%) and focused on US populations (76%); the most studied services were
diagnostic imaging in low-risk prostate and breast cancer. Few studies evaluated
active cancer therapeutics or interventions aimed at reducing overuse. Rates of
overuse varied widely among services and among studies of the same service.
CONCLUSIONS: Despite recent attention to overuse in cancer, evidence identifying
areas of overuse remains limited. Broader investigation, including assessment of
active cancer treatment, is critical for identifying improvement targets to
optimize value in cancer care.
PMID- 28498200
TI - Evaluating the Veterans Choice Program: Lessons for Developing a High-performing
Integrated Network.
PMID- 28498201
TI - An Open Letter to the PA Profession.
PMID- 28498202
TI - Partial Facial Paralysis as a Model for Prophylactic Botulinum Toxin Use for the
Prevention of Facial Rhytides.
PMID- 28498203
TI - Superficial CD34-Positive Fibroblastic Tumor Successfully Treated With Mohs
Micrographic Surgery.
PMID- 28498204
TI - ASDS Guidelines Task Force: Consensus Recommendations Regarding the Safety of
Lasers, Dermabrasion, Chemical Peels, Energy Devices, and Skin Surgery During and
After Isotretinoin Use.
AB - BACKGROUND: Currently, the isotretinoin (13-cis-retinoic acid) package insert
contains language advising the discontinuation of isotretinoin for 6 months
before performing cosmetic procedures, including waxing, dermabrasion, chemical
peels, laser procedures, or incisional and excisional cold-steel surgery. It is
common practice to follow this standard because of concerns regarding reports of
sporadic adverse events and increased risk of scarring. OBJECTIVE: To develop
expert consensus regarding the safety of skin procedures, including resurfacing,
energy device treatments, and incisional and excisional procedures, in the
setting of concurrent or recent isotretinoin use. MATERIALS AND METHODS: The
American Society for Dermatologic Surgery authorized a task force of content
experts to review the evidence and provide guidance. First, data were extracted
from the literature. This was followed by a clinical question review, a consensus
Delphi process, and validation of the results by peer review. RESULTS: The task
force concluded that there is insufficient evidence to justify delaying treatment
with superficial chemical peels and nonablative lasers, including hair removal
lasers and lights, vascular lasers, and nonablative fractional devices for
patients currently or recently exposed to isotretinoin. Superficial and focal
dermabrasion may also be safe when performed by a well-trained clinician.
PMID- 28498205
TI - In the Toolbox: The Dual Action Nail Clipper.
PMID- 28498206
TI - Allograft Dermal Matrix for Restoration of Facial Contour Deformities.
PMID- 28498207
TI - The Kinetics of Reversible Hyaluronic Acid Filler Injection Treated With
Hyaluronidase.
AB - BACKGROUND: Hyaluronidase is an enzyme capable of dissolution of hyaluronic acid
(HA). There is a lack of evidence-based research defining time- and concentration
dependent reversal of HA filler using hyaluronidase. OBJECTIVE: To explore the
efficacy of different concentrations of hyaluronidase in digesting commercially
available HA-based reversible fillers-Belotero Balance (BEL), Juvederm Ultra XC
(JUVXC), Juvederm Ultra Plus (JUVX+), Juvederm Voluma XC (JUVV), Restylane-L
(RESL), Restylane Silk (RESS), and Perlane/Restylane Lyft (RESLYFT). MATERIALS
AND METHODS: This was a blinded randomized study involving 15 participants.
Participants received HA filler injection into their back, followed by no
secondary injection, or injection with normal saline, 20 or 40 units of
hyaluronidase. Using a 5-point palpation scale, the degradation of HA filler was
monitored over 14 days. RESULTS: In the authors' study, there is a significant
decrease in HA filler degradation using 20 and 40 units of hyaluronidase compared
with no secondary injection or normal saline. There is no significant difference
in HA filler dissolution when comparing 20 to 40 units of hyaluronidase.
CONCLUSION: Lower concentrations of hyaluronidase may be just as effective as
higher concentrations to degrade HA filler in situations where the reversal of
cutaneous augmentation with HA filler arises.
PMID- 28498208
TI - Transient Nerve Damage After Microfocused Ultrasound With Visualization.
PMID- 28498210
TI - Repair of a Large Submental Defect.
PMID- 28498209
TI - Rate of Surgical Site Infections With New Protocol of Prophylactic Antibiotic Use
in Dermatologic Surgery.
PMID- 28498211
TI - Sarcoidosis Discovered During Mohs Surgery for Basal Cell Carcinoma.
PMID- 28498212
TI - ACSM Clinician Profile.
PMID- 28498213
TI - Thunderstorm Asthma, Relative Anemia, and Football Carnage.
PMID- 28498215
TI - Brachial Plexopathy.
PMID- 28498216
TI - When Is It Safe to Run? Applying Four Pain Rules to Running Participation.
PMID- 28498217
TI - Make Sport Great Again: The Use and Abuse of the Therapeutic Use Exemptions
Process.
PMID- 28498218
TI - In Place But Not Always Used: Automated External Defibrillators in Amateur
Football.
PMID- 28498219
TI - Premarathon Evaluations: Is There a Role for Runner Prerace Medical Screening and
Education to Reduce the Risk of Medical Complications?
AB - There is irrefutable evidence that regular participation in physical activity has
substantial health benefits, and as such participation in mass community-based
sports events should be supported. However, with the promotion of physical
activity comes the potential risk of medical complications during an acute
exercise session, with this risk varying according to the risk factor profile of
an individual and the nature of the event. The demographics of marathon race
entrants changed over the past two to three decades, and currently about 50% of
runners are older than 40 yr. A consolidated view of previously published
research shows that in a marathon with a field of 50,000 runners for example, the
medical staff will, on average, encounter a sudden death every 2 to 3 yr, a
sudden cardiac arrest every year, 25 runners that present with a serious medical
complication requiring specialized management or hospitalization, and 1000
runners that require medical attention. Runners may have several intrinsic risk
factors that can predispose them to serious acute cardiovascular or other serious
noncardiac medical complications on race day. This intrinsic risk can be
exacerbated by several extrinsic risk factors as well. As health care
professionals, we are obliged to give the best medical advice to individuals who
wish to participate in moderate- and high-intensity endurance activities, and at
the same time reduce their risk of a medical complication during exercise.
Preliminary data indicate that an online prerace medical screening and targeted
educational intervention program can be successfully implemented and is effective
in reducing the risk of acute medical complications during a race.
PMID- 28498220
TI - Patient Presentations and Medical Logistics at Full and Half Ironman Distance
Triathlons.
AB - We describe logistical challenges, illness/injury rates, as well as medical and
ambulance transfer rates (ATR) at an annual large-scale half/full triathlon in a
remote location. Prospective observational study; registry data. Data on patient
presentation rates, percentage of patients transferred by ambulance, transfer to
hospital rates (TTHR), ATR, and medical usage rates were collected and analyzed.
In total, 1923 athletes participated in the 2016 triathlon (1404 in the full
length race and 519 in the half) and 181 patient encounters were documented. The
patient presentation rate (PPR) was 94 in 1000 patients, and 1.6% of patients
seen onsite required offsite medical care. TTHR and ATR were 1.6 in 1000 and 0.5
in 1000, respectively. Gastrointestinal issues were the most common presentation
(50/181; 27.6%), followed by musculoskeletal injury (46/181; 25.4%) and
nonspecific dizziness (37/181; 20.4%). The incorporation of a coordinated event
medical plan and team, with integrated on-course and at-finish coverage, may have
minimized presentations of patients to local health care services; therefore,
decreasing the effect on the local ambulance service and health infrastructure of
the host community.
PMID- 28498221
TI - Optimizing Marathon Race Safety Using an Incident Command Post Strategy.
PMID- 28498222
TI - Ultrasonic Percutaneous Tenotomy for Recalcitrant Calcific Triceps Tendinosis in
a Competitive Strongman: A Case Report.
PMID- 28498223
TI - Bedside Ultrasound Diagnosis of Quadriceps Tendon Rupture and Avulsed Patella.
PMID- 28498224
TI - Core Training in Low Back Disorders: Role of the Pilates Method.
AB - The Pilates method is a system of exercises developed by Joseph Pilates, which
emphasizes recruitment and strengthening of the core muscles, flexibility, and
breathing, to promote stability and control of movement. Its focus bears
similarity to current evidence-based exercise programs for low back disorders.
Spinal stability is a function of three interdependent systems, osseoligamentous,
muscular, and neural control; exercise addresses both the muscular and neural
function. The "core" typically refers to the muscular control required to
maintain functional stability. Prior research has highlighted the importance of
muscular strength and recruitment, with debate over the importance of individual
muscles in the wider context of core control. Though developed long before the
current evidence, the Pilates method is relevant in this setting and clearly
relates to current evidence-based exercise interventions. Current literature
supports the Pilates method as a treatment for low back disorders, but its
benefit when compared with other exercise is less clear.
PMID- 28498225
TI - Rehabilitation and Prevention of Proximal Hamstring Tendinopathy.
AB - Proximal hamstring tendinopathy (PHT) comprises a small but significant portion
of hamstring injuries in athletes, especially runners. PHT is a chronic condition
that is clinically diagnosed but can be supported with imaging. The main
presenting complaint is pain in the lower gluteal or ischial region that may or
may not radiate along the hamstrings in the posterior thigh. There is little
scientific evidence on which to base the rehabilitation management of PHT.
Treatment is almost always conservative, with a focus on activity modification,
addressing contributing biomechanical deficiencies, effective tendon loading
including eccentric training, and ultrasound-guided interventional procedures
which may facilitate rehabilitation. Surgery is limited to recalcitrant cases or
those involving concomitant high-grade musculotendinous pathology. The keys to
PHT management include early and accurate diagnosis, optimal rehabilitation to
allow for a safe return to preinjury activity level, and preventative strategies
to reduce risk of reinjury.
PMID- 28498226
TI - Anterior Cruciate Ligament Injury: Return to Play, Function and Long-Term
Considerations.
AB - Anterior cruciate ligament tears are common and affect young individuals who
participate in jumping and pivoting sports. After injury many individuals undergo
ligament reconstruction (ACLR) but do not return to play, suffer recurrent injury
and osteoarthritis. Outcome studies show that after ACLR, 81% of individuals
return to sports, 65% return to their preinjury level and 55% return to
competitive sports. Systematic reviews place the risk of ipsilateral retears at
5.8% and contralateral injuries at 11.8%, with recent reports of over 20% failure
rate. Approximately 20% to 50% of patients will have evidence of OA within 10 to
20 yr. Factors important in reducing complications include timing of surgery,
individualized return to play protocols, and prevention programs for injury.
Further understanding of the factors that increase return to play percentages,
reduce the risk of recurrent injury and improve long-term outcomes after ACL
injury is needed to reduce the burden of these injuries on society.
PMID- 28498227
TI - Mechanisms and Treatments for Shoulder Injuries in Overhead Throwing Athletes.
AB - Shoulder injuries in overhead throwing athletes are very common. Throwing volume
and mechanical forces that are placed on the glenohumeral joint and associated
soft tissue structures are contributors. Poor biomechanics and weak links in the
kinetic chain place this athletic population at increased risk for shoulder
injuries. Common biomechanical deficiencies in overhead throwing athletes
typically involve poor sequential timing of muscle activity and insufficient
coordination also presented in shoulder elevation and other functional tasks.
Kinetic chain deficits will lead to injury due to poor transference of energy
from the lower extremities to the dominant upper extremity. Correction of these
deficits involves effective treatment and prevention strategies. These include
core and hip strengthening, balance training, optimize timing of biomechanical
phases and events for each throwing movement, and following recommended rest
guidelines. This article will synopsize current evidence of sport-specific injury
mechanisms, injury treatment, and prevention of the shoulder in overhead throwing
athletes.
PMID- 28498228
TI - Psychological Issues Related to Illness and Injury in Athletes and the Team
Physician: a Consensus Statement-2016 Update.
PMID- 28498229
TI - Not Missing the Future: A Call to Action for Investigating the Role of
Regenerative Medicine Therapies in Pediatric/Adolescent Sports Injuries.
AB - In August 2016, a group including sport medicine clinicians, researchers, and a
bioethicist met in Vail, Colorado to discuss regenerative medicine and its
potential role in youth sports injuries. There was consensus that a call to
action is urgently needed to understand the current evidence base, the risks and
rewards, and future directions of research and clinical practice for regenerative
medicine therapies in youth sports. We present here a summary of our meeting,
which was supported by the National Youth Sports Health and Safety Institute
(NYSHSI), a partnership between the American College of Sports Medicine (ACSM)
and Sanford Health. The group's goal is to educate practitioners and the public,
and to pioneer a means of accumulating meaningful clinical data on regenerative
medicine therapies in pediatric and adolescent athletes.
PMID- 28498230
TI - High Frequency of Neuroimaging Abnormalities Among Pediatric Patients With Sepsis
Who Undergo Neuroimaging.
AB - OBJECTIVES: This study was intended to describe and correlate the neuroimaging
findings in pediatric patients after sepsis. DESIGN: Retrospective chart review.
SETTING: Single tertiary care PICU. PATIENTS: Patients admitted to Cincinnati
Children's Hospital Medical Center with a discharge diagnosis of sepsis or septic
shock between 2004 and 2013 were crossmatched with patients who underwent
neuroimaging during the same time period. INTERVENTIONS: All neuroimaging studies
that occurred during or subsequent to a septic event were reviewed, and all new
imaging findings were recorded and classified. As many patients experienced
multiple septic events and/or had multiple neuroimaging studies after sepsis, our
statistical analysis utilized the most recent or "final" imaging study available
for each patient so that only brain imaging findings that persisted were
included. MEASUREMENTS AND MAIN RESULTS: A total of 389 children with sepsis and
1,705 concurrent or subsequent neuroimaging studies were included in the study.
Median age at first septic event was 3.4 years (interquartile range, 0.7-11.5).
Median time from first sepsis event to final neuroimaging was 157 days
(interquartile range, 10-1,054). The most common indications for final imaging
were follow-up (21%), altered mental status (18%), and fever/concern for
infection (15%). Sixty-three percentage (n = 243) of final imaging studies
demonstrated abnormal findings, the most common of which were volume loss (39%)
and MRI signal and/or CT attenuation abnormalities (21%). On multivariable
logistic regression, highest Pediatric Risk of Mortality score and presence of
oncologic diagnosis/organ transplantation were independently associated with any
abnormal final neuroimaging study findings (odds ratio, 1.032; p = 0.048 and odds
ratio, 1.632; p = 0.041), although early timing of neuroimaging demonstrated a
negative association (odds ratio, 0.606; p = 0.039). The most common abnormal
finding of volume loss was independently associated with highest Pediatric Risk
of Mortality score (odds ratio, 1.037; p = 0.016) and oncologic diagnosis/organ
transplantation (odds ratio, 2.207; p = 0.001) and was negatively associated with
early timing of neuroimaging (odds ratio, 0.575; p = 0.037). CONCLUSIONS: The
majority of pediatric patients with sepsis and concurrent or subsequent
neuroimaging have abnormal neuroimaging findings. The implications of this high
incidence for long-term neurologic outcomes and follow-up require further
exploration.
PMID- 28498231
TI - Metrics to Assess Extracorporeal Membrane Oxygenation Utilization in Pediatric
Cardiac Surgery Programs.
AB - OBJECTIVES: Only a small fraction of pediatric cardiac surgical patients are
supported with extracorporeal membrane oxygenation following cardiac surgery, but
extracorporeal membrane oxygenation use is more common among those undergoing
higher complexity surgery. We evaluated extracorporeal membrane oxygenation
metrics indexed to annual cardiac surgical volume to better understand
extracorporeal membrane oxygenation use among U.S. cardiac surgical programs.
DESIGN: Retrospective analysis SETTING:: Forty-three U.S. Children's Hospitals in
the Pediatric Health Information System that performed cardiac surgery and used
extracorporeal membrane oxygenation. PATIENTS: All patients (< 19 yr) undergoing
cardiac surgery during January 2003 to July 2014. INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: Both extracorporeal membrane oxygenation use and
surgical mortality were risk adjusted using Risk Adjustment for Congenital Heart
Surgery 1. Extracorporeal membrane oxygenation metrics indexed to annual cardiac
surgery cases were calculated for each hospital and the metric values divided
into quintiles for comparison across hospitals. Among 131,786 cardiac surgical
patients, 3,782 (2.9%) received extracorporeal membrane oxygenation. Median case
mix adjusted rate of extracorporeal membrane oxygenation use was 2.8%
(interquartile range, 1.6-3.4%). Median pediatric cardiac case mix adjusted
surgical mortality was 3.5%. Extracorporeal membrane oxygenation-associated
surgical mortality was 1.3% (interquartile range, 0.7-1.6%); without
extracorporeal membrane oxygenation, median case mix adjusted surgical mortality
would increase from 3.5% to 5.0%. Among patients who died, 36.7% (median) were
supported with extracorporeal membrane oxygenation. The median reduction in case
mix adjusted surgical mortality from extracorporeal membrane oxygenation surgical
survival was 30.1%. The median extracorporeal membrane oxygenation free surgical
survival was 95% (interquartile range, 94-96%). Centers with less than 150 annual
surgical cases had significantly lower median extracorporeal membrane oxygenation
use (0.78%) than centers with greater than 275 cases (>= 2.8% extracorporeal
membrane oxygenation use). Extracorporeal membrane oxygenation use and mortality
varied within quintiles and across quintiles of center annual surgical case
volume. CONCLUSIONS: Risk adjusted extracorporeal membrane oxygenation metrics
indexed to annual surgical volume provide potential for benchmarking as well as a
greater understanding of extracorporeal membrane oxygenation utilization,
efficacy, and impact on cardiac surgery mortality.
PMID- 28498232
TI - Antihypertensive Drugs Aliskiren, Nebivolol, and Olmesartan Reduce Hypertension
by Reducing Endothelial Microparticles and Regulating Angiogenesis.
AB - The accelerated generation of endothelial microparticles (EMPs) and impaired
angiogenesis are the markers of vascular pathology during various cardiovascular
and inflammatory conditions including hypertension. Because studies comparing the
effects of antihypertensive agents on these 2 parameters are limited, this study
was designed to compare the effects of 3 antihypertensive agents: aliskiren,
nebivolol, and olmesartan, on the EMP generation and angiogenesis. Changes in the
hemodynamic parameters and serum EMP count were determined after 3 weeks of the
drug treatments [aliskiren (30 mg/kg), nebivolol (10 mg/kg), or olmesartan (5
mg/kg) per orally] in L-NAME-induced rat model of hypertension. The 3 drugs
prevented the rise in blood pressure and EMP count to a similar extent.
Furthermore, nebivolol was found to possess more potent and concentration
dependent antiangiogenic activity compared with aliskiren, whereas olmesartan was
devoid of such an effect. The EMPs generated by virtue of the respective drug
treatments were found to be involved in mediating the antiangiogenic effect of
nebivolol and aliskiren. In addition, olmesartan treatment also resulted in the
increased eNOS expression. The results of this study show that the
antihypertensive drugs, viz. aliskiren, nebivolol, and olmesartan, regulate the
vascular health by their differential effects on the EMP generation and
angiogenesis.
PMID- 28498233
TI - Wearable Sensor Technology Efficacy in Peripheral Vascular Disease (wSTEP): A
Randomized Controlled Trial.
AB - OBJECTIVE: To evaluate the effect of using wearable activity monitors (WAMs) in
patients with intermittent claudication (IC) within a single-center randomized
controlled trial. BACKGROUND: WAMs allow users to set daily activity targets and
monitor their progress. They may offer an alternative treatment to supervised
exercise programs (SEPs) for patients with IC. METHODS: Thirty-seven patients
with IC were recruited and randomized into intervention or control group. The
intervention consisted of a feedback-enabled, wrist-worn activity monitor (WAM)
in addition to access to SEP. The control group was given access to SEP only. The
outcome measures were maximum walking distance (MWD), claudication distance (CD),
and quality of life as measured by the VascuQol questionnaire. Participants were
assessed upon recruitment, and at 3, 6, and 12 months. RESULTS: Patients in the
WAM group showed significant improvement in MWD at 3 and 6 months (80-112 m, to
178 m; P < 0.001), which was sustained at 12 months. The WAM group also increased
CD (40 vs 110 m; P < 0.001) and VascuQol score (4.7 vs 5.8; P = 0.004). The
control group saw a temporary increase in VascuQol score at 6 months (4.5 vs 4.7;
P = 0.028), but no other improvements in MWD or CD were observed. Significantly
higher improvements in MWD were seen in the WAM group compared with that in the
control group at 6 months (82 vs -5 m; P = 0.009, r = 0.47) and 12 months (69 vs
7.5 m; P = 0.011, r = 0.52). CONCLUSIONS: The study demonstrates the significant,
sustained benefit of WAM-led technologies for patients with IC. This potentially
resource-sparing intervention is likely to provide a valuable adjunct or
alternative to SEP.
PMID- 28498234
TI - Long-term Outcomes of Carotid Endarterectomy Versus Stenting in a Multicenter
Population-based Canadian Study.
AB - OBJECTIVE: To compare the long-term outcomes of patients treated with carotid
endarterectomy and carotid-artery stenting. BACKGROUND: Evidence for the long
term safety and efficacy of carotid-artery stenting compared with endarterectomy
is accumulating from randomized trials. However, comparative data on the long
term outcomes of carotid revascularization strategies in real world practice are
lacking. METHODS: We conducted a population-based, multicenter, observational
cohort study using validated linked databases from Ontario, Canada. We identified
all individuals treated with carotid endarterectomy and stenting (2002-2014), and
followed them up to 2015. We compared long-term (up to 13 years) and 30-day
outcomes of each strategy using multilevel multivariable Cox proportional-hazards
models, and conducted confirmatory analyses using propensity-score matching
methods. RESULTS: In all, 15,525 patients received carotid-artery
revascularization. Rate of the primary composite outcome of 30-day death, stroke,
or myocardial infarction plus any stroke during 13-year follow-up was higher with
stenting (16.3%) compared with endarterectomy (9.7%) [adjusted hazard ratio (HR)
1.57, 95% confidence interval (CI) 1.43-1.73, P < 0.001). The increased risk with
stenting was observed regardless of age, sex, intervention year, carotid-artery
symptoms, or diabetes. The primary outcome was driven by higher rates of 30-day
stroke (adjusted HR 1.59, 95% CI 1.29-1.95), 30-day death (adjusted HR 2.62, 95%
CI 2.20-3.13), and long-term stroke >30 days after the procedure (adjusted HR
1.47, 95% CI 1.36-1.59) with stenting; 30-day myocardial infarction was lower
with stenting (adjusted HR 0.70, 95% CI 0.57-0.86). These results were confirmed
with 1:2 propensity-score matching (HR for primary composite outcome with
stenting 1.55, 95% CI 1.31-1.83, P < 0.001). CONCLUSIONS: Compared with carotid
endarterectomy, stenting was associated with an early and sustained approximately
55% increased hazard for major adverse events over long-term follow-up. Although
nonrandomized, these results raise potential concerns about the
interchangeability of carotid endarterectomy and stenting in the context of
actual clinical practice.
PMID- 28498235
TI - Hospital Minimally Invasive Surgery Utilization for Gastrointestinal Cancer.
AB - OBJECTIVE: The aim of the study was to evaluate the impact of receiving care at
high minimally invasive surgery (MIS)-utilizing hospitals BACKGROUND:: MIS
techniques are used across surgical specialties. The extent of MIS utilization
for gastrointestinal (GI) cancer resection and impact of receiving care at high
utilizing hospitals is unclear. METHODS: This is a retrospective cohort study of
137,581 surgically resected esophageal, gastric, pancreatic, hepatobiliary,
colon, and rectal cancer patients within the National Cancer Data Base (2010
2013). Disease-specific, hospital-level, reliability-adjusted MIS utilization
rates were calculated to evaluate perioperative outcomes. Among patients for whom
adjuvant chemotherapy (AC) was indicated, the association between days to AC and
hospital MIS utilization was examined using generalized estimating equations.
Association with risk of death was evaluated using multivariable Cox regression.
RESULTS: Disease-specific MIS use increased significantly [42.0%-68.3% increase;
trend test, P < 0.001 for all except hepatobiliary (P = 0.007)] over time. Most
hospitals [range-30.3% (colon); 92.9% (pancreatic)] were low utilizers (<=30% of
cases). Higher MIS utilization is associated with increased lymph nodes examined
(P < 0.001, all) and shorter length of stay (P < 0.001, all). Each 10% increase
in MIS utilization is associated with fewer days to AC [3.3 (95% confidence
interval, 1.2-5.3) for MIS gastric; 3.3 ([0.7-5.8) for open gastric; 1.1 (0.3
2.0) days for open colon]. An association between MIS utilization and risk of
death was observed for colon [Q2-hazard ratio (HR) 0.96 (0.89-1.02); Q3-HR 0.91
(0.86-0.98); Q4-HR 0.87 (0.82-0.93)] and rectal cancer [Q2-HR 0.89 (0.76-1.05);
Q3-HR 0.84 (0.82-0.97); Q4-HR 0.86 (0.74-0.98)]. CONCLUSIONS: Most hospitals
treating GI malignancies are low MIS utilizers. Our findings may reflect real
world MIS effectiveness for oncologic resection and could be useful for
identifying hospitals with infrastructure and/or processes beneficial for
multimodality cancer care.
PMID- 28498236
TI - Feasibility of Transabdominal Cardiophrenic Lymphnode Dissection in Advanced
Ovarian Cancer: Initial Experience at a Tertiary Center.
AB - OBJECTIVES: The purpose of this retrospective report is to define the safety and
feasibility, based on our preliminary experience, of surgical transdiaphragmatic
resection of enlarged cardiophrenic lymph nodes (CPLNs), as a part of upfront
debulking surgery. Supradiaphragmatic nodes located between the diaphragm and the
heart are frequently a location for lymph node metastasis in advanced ovarian
cancer, and their removal is aimed to obtain no gross residual disease at the
primary cytoreductive surgery often requiring aggressive surgical procedures.
PATIENTS AND METHODS: Between May 2012 and October 2016, a total of 22 patients
among 443 with advanced high-grade serous ovarian cancer underwent cytoreductive
procedures involving transdiaphragmatic resection of enlarged CPLNs at European
Institute of Oncology in Milan. RESULTS: All patients who underwent CPLN
resection had an extensive disease (median peritoneal cancer index, 18), and more
than 77% required complex surgical procedures (complexity score, 3). No residual
abdominal disease less than 5 mm at the end of surgery was described in 20 (90%)
out of 22. All patients but one had confirmed CPLN positive nodes at
histopathological study. The average operative time was 333 min (range, 244-455
min), and the average estimated blood loss was 1000 mL (range, 400-2000 mL).
Blood transfusion was necessary in 13 out of 22 patients. Only 7 (33%) out of 21
patients required chest tube placement during the postoperative period.
CONCLUSIONS: Transdiaphragmatic enlarged CPLN resection seems to be safe and
feasible procedure when indicated to achieve no or minimal tumor residual
disease. Nevertheless, its impact on survival of patients with stage IV ovarian
cancer needs to be determined.
PMID- 28498237
TI - Enhanced Recovery After Surgery for Advanced Ovarian Cancer: A Systematic Review
of Interventions Trialed.
AB - OBJECTIVES: We sought to summarize the evidence for interventions aiming at
enhanced recovery after surgery (ERAS) in ovarian cancer through a systematic
review. METHODS: We searched MEDLINE, EMBASE, and The Cochrane Library for
studies testing ERAS interventions in patients undergoing surgery for ovarian
cancer. Study selection and data extraction were done independently by 2
reviewers with disagreements resolved by discussion with a senior, third
reviewer. RESULTS: We identified 25 studies including 1648 participants with
ovarian cancer. Nine observational studies addressed ERAS protocols. Four of them
were prospective, and 3 included historical controls. The other 16 studies
reported single interventions, for example, early feeding, omission of pelvic
drains, early orogastric tube removal, Doppler-guided fluid management, and
patient-controlled epidural analgesia. Early feeding protocols were tested in 7
of the 12 randomized trials. Early feeding appeared to be safe and was associated
with significantly faster recovery of bowel function. CONCLUSIONS: Few studies
have specifically studied ERAS interventions in ovarian cancer. All studies on
protocols including multiple interventions were susceptible to bias. Early
feeding is the intervention that is best supported by randomized trials.
Application of evidence for ERAS derived from nonovarian cancer is challenged by
the differences not only in the scope of surgery but also in ovarian cancer
patients' comorbidities. Postoperative morbidity is particularly high in these
patients because of their poor nutritional status, perioperative fluids shifts,
and long operating times. These patients may also show excessive response to
surgical stress. Innovative, randomized trials are needed to reliably determine
the feasibility, safety, and effectiveness of specific ERAS interventions in
ovarian cancer.
PMID- 28498238
TI - Nomogram Predicting Overall Survival in Operable Cervical Cancer Patients.
AB - OBJECTIVE: Nomograms are widely used as predictive tools to predict oncological
outcomes intuitively and precisely. The aim of our study was to develop a
nomogram for predicting overall survival (OS) of patients with early stage
cervical cancer. METHODS: In this retrospective study, the clinical,
pathological, and hematological data and prognosis of 795 cervical cancer
patients were investigated. We identified and incorporated independent
significant prognostic factors for OS to develop a nomogram. The predictive
accuracy and discriminative ability were measured by concordance index. RESULTS:
By univariable analysis and subsequent multivariable analysis, we identified body
mass index, albumin, platelet, leukocyte, tumor differentiation, and the status
of the pelvic lymph node (PLN) (all P < 0.05) as independent prognostic factors.
The concordance index of the nomogram integrating these 6 variables was 0.74. The
calibration curves for probability of 3- and 5-year OS also demonstrated ideal
agreement between nomogram prediction and actual observation. CONCLUSIONS: We
developed a novel nomogram that can provide prediction of OS for patients with
early stage cervical cancer individually. Furthermore, studies are required to
validate whether it can be applied to other cohorts.
PMID- 28498239
TI - The Validity of Using Human Squamous Cell Carcinoma Associated Antigen and
Cytokeratin 19 Fragment Antigen 21-1 to Predict Postoperative Adjuvant
Radiotherapy for Nonbulky Early-Stage Squamous Cell Carcinoma of the Cervix.
AB - OBJECTIVE: There are no generally accepted biomarkers for the optimal selection
of radiotherapy-based or surgical-based treatment options for nonbulky early
stage squamous cell carcinoma of the cervix (IA1-IB1 and IIA1). The objective of
this study was to assess the value of human squamous cell carcinoma-associated
antigen (SCC-Ag) and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) in
evaluation of patients with nonbulky early-stage squamous cell carcinoma of the
cervix to determine if radiotherapy is warranted after radical surgery. METHODS:
Patients with stage IA1-IB1 and IIA1 squamous cell carcinoma of the cervix who
were treated at the Department of Gynecological Oncology, Affiliated Tumor
Hospital of Guangxi Medical University, from March 2012 to August 2014 (n = 308)
were treated with radical hysterectomy and pelvic lymphadenectomy. The levels of
SCC-Ag and CYFRA21-1 were detected by enzyme-linked immunosorbent assay before
surgery. The relationship between the concentrations of SCC-Ag and CYFRA21-1 and
risk factors was estimated through logistic regression and analysis of variance t
test. The cutoff values of these 2 markers to evaluate the need for postoperative
radiotherapy were identified and validated by receiver operating characteristic
curve and kappa consistency test, respectively. RESULTS: Serum SCC-Ag and CYFRA21
1 levels are significantly increased in patients who require postoperative
radiotherapy with a risk factor score of at least 2 (n = 162). Logistic
regression analysis revealed that deep stromal invasion and lymph node metastasis
are independent risk factors for serum SCC-Ag value, and deep stromal invasion is
an independent risk factor for the serum CYFRA21-1 value. Receiver operating
characteristic curve revealed that the best predictive cutoff points of SCC-Ag
and CYFRA21-1 values were 1.425 and 3.210 ng/mL, respectively. These results were
validated by the kappa consistency test applied to a validation group of
patients. The results suggest that most patients with SCC-Ag and CYFRA21-1 values
of at least 1.425 and 3.210 ng/mL, respectively, require postoperative
radiotherapy. CONCLUSIONS: Detection of the levels of SCC-Ag and CYFRA21-1 may
help guide an individual primary treatment plan for patients with nonbulky early
stage squamous cell carcinoma of the cervix.
PMID- 28498240
TI - Simple Vaginal Trachelectomy: A Valuable Fertility-Preserving Option in Early
Stage Cervical Cancer.
AB - OBJECTIVE: Radical trachelectomy is a valid alternative for the treatment of
early-stage cervical cancer in young women who wish to preserve fertility
potential. Recent data indicate that even less radical surgery could be performed
in low-risk cases. The objective of our study was to evaluate the safety of
simple vaginal trachelectomy and node assessment in patients with low-risk, early
stage cervical cancer (<2 cm). METHODS: From May 2007 to July 2016, 35 women
underwent a simple vaginal trachelectomy with laparoscopic sentinel lymph node
mapping + pelvic node dissection. Data were collected prospectively in a
computerized database. Descriptive statistics and Kaplan-Meier estimate were used
for analysis. RESULTS: Patients' median age was 29 years, and 24 (69%) were
nulliparous. Eight had stage IA1 with lymphovascular space invasion, 9 a stage
IA2, and 18 a stage IB1. Nineteen (54%) had squamous histology, 13 (37%) had
adenocarcinoma, and 3 had other histologic findings. The median operating room
time was 148 minutes (90-240 minutes), and median blood loss was 50 mL (25-200
mL). On final pathology, lymph nodes were negative in all patients, except 2
cases with isolated tumor cells. Twenty-two patients (63%) had either no residual
disease in the trachelectomy specimen (n = 15) or residual dysplasia only (n =
7). With a median follow-up of 42 months (1-100 months), 1 local recurrence
occurred treated initially with chemoradiation and then a pelvic exenteration.
The recurrence-free survival at 48 months is 96.7%. There were 25 pregnancies: 5
(20%) ended in the first trimester, 2 delivered prematurely at 34.4 and at 35
weeks, and all the others (18 [72%]) delivered at more than 36 weeks.
CONCLUSIONS: Based on our experience, simple trachelectomy and nodes appear to be
a safe fertility-preserving surgery in well-selected patients with small-volume
cervical cancer. Obstetric outcome appears favorable.
PMID- 28498241
TI - Serum Human Chorionic Gonadotropin Normogram for the Detection of Gestational
Trophoblastic Neoplasia.
AB - OBJECTIVE: The aim of this study was to develop a serum human chorionic
gonadotropin (hCG) normogram for both uneventful complete and partial
hydatidiform moles in the first-trimester ultrasound era. METHODS: An hCG
normogram for both complete and partial hydatidiform moles was constructed, based
on 639 patients with uneventful serum hCG regression after evacuation between
1990 and 2014. Serum hCG was measured by an in-house-developed radioimmunoassay,
detecting both intact hCG and free beta-subunit. It has been in use for all serum
measurements sent to the Dutch Central Registry for Hydatidiform Moles since
1977. RESULTS: Since introduction of routine first-trimester ultrasonography,
lower pre-evacuation and follow-up serum hCG concentrations were observed. When
compared with complete hydatidiform moles, patients with a partial hydatidiform
mole had significantly lower pre-evacuation serum hCG concentration (median, 4400
and 875 ng/mL, respectively; P < 0.001) and earlier hCG normalization (median, 7
and 6 weeks, respectively; P < 0.001) but higher gestational age (mean, 11.5 and
13.0 weeks, respectively; P < 0.001). For both complete and partial hydatidiform
moles, 95% of patients reached normal serum hCG concentrations within 14 weeks
after evacuation. CONCLUSIONS: A normogram for the detection of gestational
trophoblastic neoplasia was developed for complete and partial hydatidiform
moles. Although interesting from a scientific perspective, the small divergence
in hCG regression between complete and partial hydatidiform moles will be of
little importance in clinical practice, as actual differences in regression will
encompass only days. To promote clarity and unity in daily practice, we therefore
propose a combined normogram to be used as a reference guideline for follow-up
after evacuation of a hydatidiform mole. This normogram will be compliant with
patients in today's clinical practice.
PMID- 28498242
TI - Rivaroxaban Used in the Treatment Patients With Gynecologic Cancer and Venous
Thromboembolism: The Experience of Instituto Nacional de Cancer-Rio de Janeiro,
Brazil.
AB - INTRODUCTION: Venous thromboembolism (VTE) is a major complication of malignant
diseases and is a frequent cause of death in patients with cancer. Managing
anticoagulation in these patients is challenging because of the high risk of
recurrent VTE and bleeding events. Rivaroxaban is an oral anticoagulant that
provides rapid onset of anticoagulation. OBJECTIVE: The aim of this study was to
describe the complications of rivaroxaban and potentially associated factors in
patients with gynecologic cancer and VTE. METHODS: This was an observational
study in women with gynecological cancer who developed VTE and were treated with
15 and 20 mg rivaroxaban at Instituto Nacional de Cancer from July 2014 to July
2015. RESULTS: Forty-one patients were treated with rivaroxaban. Most patients
were younger than 60 years and presented cervical cancer; 58.5% of women did not
have complications, thus remaining at a dose of 20 mg/d. Because of
complications, 12.2% had the dose reduced to 15 mg/d, 12.2% had the drug
suspended, 7.3% had progressive worsening of the disease with suspension of
anticoagulation, and 9.8% progressed to death because of progression of the
disease. CONCLUSIONS: Rivaroxaban has been documented as a low-cost, easily
controlled option compared with standard therapy. Most participants in this study
had no complications. However, it was not possible to assess associations with
statistical significance. Further analytical studies with larger samples are
required to evaluate the safety and efficacy of this treatment in patients with
gynecologic cancer.
PMID- 28498243
TI - A Controlled Study on Vaginal Blood Flow During Sexual Arousal Among Early-Stage
Cervical Cancer Survivors Treated With Conventional Radical or Nerve-Sparing
Surgery With or Without Radiotherapy.
AB - OBJECTIVE: Sexual problems among cervical cancer survivors may in part be caused
by reduced vaginal blood flow due to damaged hypogastric nerves during radical
hysterectomy with pelvic lymphadenectomy and/or by radiation-induced vaginal
changes after pelvic radiotherapy. A nerve-sparing modification of radical
hysterectomy (NSRH) may preserve vaginal blood flow. Vaginal blood flow during
sexual arousal was compared between different treatment modalities. METHODS: We
investigated premenopausal women treated for early-stage cervical cancer with
radical hysterectomy (n = 29), NSRH (n = 28), NSRH with radiotherapy (n = 14),
and controls (n = 31). Genital arousal and subjective sexual arousal in response
to sexual stimuli were measured using vaginal photoplethysmography and a
questionnaire. Results were compared by using a between-study (treatment groups)
by within-study (stimulus) design. RESULTS: Participants were aged 29 to 51 years
(mean, 42 years) and at 1 to 14 years (mean, 5 years) after treatment. Measured
vaginal blood flow in women treated with NSRH was similar to controls. Women
treated with radical hysterectomy had a significantly lower vaginal blood flow
compared with controls overall and lower compared with the NSRH group during
sexual stimulation. Women treated with radiotherapy had a vaginal blood flow
intermediate between the other groups without significant differences. The erotic
films were equally effective in enhancing subjective sexual arousal among
treatment groups. CONCLUSIONS: Cervical cancer treatment with radical
hysterectomy disrupts the vaginal blood flow response, and this may be prevented
by conducting an NSRH. Treatment with radiotherapy did not significantly impact
vaginal blood flow, but further investigation is needed with a larger sample.
PMID- 28498244
TI - Identifying Lynch Syndrome in Women Presenting With Endometrial Carcinoma Under
the Age of 50 Years.
AB - BACKGROUND: Lynch syndrome (LS) is an inherited disorder associated with genetic
predisposition to endometrial, colorectal, ovarian, and other cancers. There is
consensus for the necessity of assessment for LS in view of the established
survival benefits for identified patients and affected family members. The debate
regarding the best screening policy is far from being concluded. OBJECTIVES: The
aim of this study was to evaluate a realistic protocol for identifying LS
families by assessing young women with a diagnosis of endometrial cancer (EC).
METHODS: Consecutive cases of women with a diagnosis of endometrioid EC younger
than 50 years were recruited. A complete 3-generation pedigree was drawn and
assessed against the Amsterdam II criteria. Tumor DNA microsatellite instability
and immunohistochemistry testing for the expression of mismatch repair (MMR)
proteins MLH1, MSH2, MSH6, and PMS2 was offered to all patients. MLH1 gene
promoter methylation and EPCAM gene deletion testing were also offered where
appropriate. Genetic counseling and MMR germline mutation tests were offered in
women with abnormal results. RESULTS: Fifty-eight women were invited, and 38
(65.5%), consented for LS assessment (95% confidence interval CI 53%-78%). A
complete data set was obtained in 35 women (60.3%). Lynch syndrome according to
clinical and/or molecular characteristics was diagnosed in 8 cases or 22.8% (95%
CI 15%-48%). There was no significant difference at the age of women with a
diagnosis of LS (median, 45 years; range, 37-48 years) compared with that of the
non-LS ones (median, 45 years; range, 31-49 years). Three pathogenic MMR
mutations were identified in the 8 cases with a diagnosis of LS, 37.5% (95% CI 5%
72%), estimating an 8.5% (95% CI 1%-19%) mutation prevalence in the study
population. CONCLUSIONS: All women with newly diagnosed EC should be assessed for
inherited predisposition. Regional policies for assessment should be developed in
accordance with available resources. Gynecologists are required to upgrade their
skills in order to identify, assess, and counsel patients with suspected or
established LS and appropriately refer to clinical genetics.
PMID- 28498245
TI - Increased Endothelial Progenitor Cell Number in Early Stage of Endometrial
Cancer.
AB - OBJECTIVES: It is generally believed that circulating endothelial cells (CECs)
and endothelial progenitor cells (EPCs) reflect the state of the endothelium, its
injury and/or repair possibilities. In different types of cancers, increased
numbers of CECs and EPCs were found, suggesting their participation in cancer
angiogenesis. The objective of this study was to determine whether, in the blood
circulation of women with early endometrial cancer, CEC and EPC levels differ
from those of healthy women of similar age. METHODS: For CEC number evaluation,
samples of peripheral blood cells of women with endometrial carcinoma and control
subjects were labeled with anti-CD31 and anti-CD45 antibodies; for EPCs, with
anti-VEGFR2 (vascular-endothelium growth factor receptor 2)/KDR and anti-CD34
antibodies. The CEC and EPC cells were then quantified by flow cytometry.
RESULTS: Endothelial progenitor cell numbers (CD34, VEGFR2/KDR) in the peripheral
blood of women with endometrial carcinoma were significantly augmented as
compared with those of control healthy women and CEC numbers (CD31, CD45) were
similar in both groups. Cancer patients were divided according to the grading
into G1 and G2 groups and according to the stage into International Federation of
Gynecology and Obstetrics (FIGO) stage IA and FIGO IB groups. Statistically
significant augmented EPC numbers were demonstrated only in G1 and FIGO IA
patients. CONCLUSIONS: These results strongly suggest new vessel formation from
recruited endothelial precursors as being involved mainly at the early stages of
tumor progression.
PMID- 28498247
TI - Practice Patterns of Hereditary Ovarian Cancer Management in Korea.
AB - OBJECTIVE: This study aims to evaluate practice patterns for managing hereditary
ovarian cancer among Korean gynecologic oncologic physicians. METHODS: Members of
the Korean Society of Gynecologic Oncology participated in the inaugural
Hereditary Gynecologic Cancer Symposium or were invited to this survey by e-mail
from January to February 2016. The survey was conducted using a self-administered
questionnaire. RESULTS: Most physicians (66.7%, 36/54) responded to draw a
pedigree of patients with a family history. The rate of genetic test
recommendations for patients at risk for ovarian cancer was high (96.3%, 52/54).
Physicians tended to select appropriate candidates for the genetic test. Of the
respondents, genetic counseling was commonly performed before the genetic test
(76.6%, 36/47) and provided by the specialist consultant(s) (78.7%, 37/47) or the
physician alone (12.8%, 6/47). Participants showed mature response to risk
management for the BRCA carriers: at least annual gynecologic surveillance
(89.4%, 42/47), recommendation for chemoprevention (76.6%, 36/47), and advice for
risk-reducing salpingo-oophorectomy (85.1%, 40/47). Risk-reducing salpingectomy
with delayed oophorectomy as an alternative to risk-reducing salpingo
oophorectomy was considered to recommend in most of respondents (91.5%, 43/47).
CONCLUSIONS: Gynecologic oncologic physicians in Korea had high awareness to
genetic risk assessment, candidate selection to genetic test, and risk-reducing
strategies for the management of hereditary ovarian cancer.
PMID- 28498246
TI - Endometrial Cancers With Activating KRas Mutations Have Activated Estrogen
Signaling and Paradoxical Response to MEK Inhibition.
AB - OBJECTIVES: The aims of this study were to determine if activating KRas mutation
alters estrogen signaling in endometrial cancer (EC) and to explore the potential
therapeutic impact of these alterations. METHODS: The Cancer Genome Atlas was
queried for changes in estrogen-regulated genes in EC based on KRas mutation
status. In vitro studies were conducted to evaluate estrogen receptor alpha
(ERalpha) phosphorylation changes and related kinase changes in KRas mutant EC
cells. The resulting effect on response to MEK inhibition, using trametinib, was
evaluated. Immunohistochemistry was performed on KRas mutant and wild-type EC
tumors to test estrogen signaling differences. RESULTS: KRas mutant tumors in The
Cancer Genome Atlas showed decreased progesterone receptor expression (P =
0.047). Protein analysis in KRas mutant EC cells also showed decreased expression
of ERalpha (P < 0.001) and progesterone receptor (P = 0.001). Although total
ERalpha is decreased in KRas mutant cells, phospho-ERalpha S118 was increased
compared with wild type. Treatment with trametinib in KRas mutant cells increased
phospho-ERalpha S167 and increased expression of estrogen-regulated genes. While
MEK inhibition blocked estradiol-stimulated phosphorylation of ERK1/2 and p90RSK
in wild-type cells, phospho-ERK1/2 and phospho-p90RSK were substantially
increased in KRas mutants. KRas mutant EC tumor specimens showed similar changes,
with increased phospho-ERalpha S118 and phospho-ERalpha S167 compared with wild
type EC tumors. CONCLUSIONS: MEK inhibition in KRas mutant cells results in
activation of ER signaling and prevents the abrogation of signaling through
ERK1/2 and p90RSK that is achieved in KRas wild-type EC cells. Combination
therapy with MEK inhibition plus antiestrogen therapy may be necessary to improve
response rates in patients with KRas mutant EC.
PMID- 28498248
TI - C1GALT1 Seems to Promote In Vitro Disease Progression in Ovarian Cancer.
AB - OBJECTIVE: Aberrant glycosylation affects many cellular properties in cancers.
The core 1 beta1,3-galactosyltransferase (C1GALT1), an enzyme that controls the
formation of mucin-type O-glycans, has been reported to regulate hepatocellular
and mammary carcinogenesis. This study aimed to explore the role of C1GALT1 in
ovarian cancer. METHODS: C1GALT1 expression was assessed in a public database
based on microarray data from 1287 ovarian cancer patients and ovarian cancerous
tissues. Lectin blotting and flow cytometry analysis were conducted to detect
changes in O-glycans on ovarian cancer cells. Effects of C1GALT1 on cell growth,
migration, and sphere formation were analyzed in C1GALT1 knockdown or
overexpressing ovarian cancer cells in vitro. Expression of cancer stemness
related genes was analyzed by quantitative reverse transcription polymerase chain
reaction. RESULTS: High C1GALT1 expression shows a trend toward association with
poor survival in ovarian cancer patients. C1GALT1 modifies O-glycan expression on
surfaces and glycoproteins of ovarian cancer cells. Knockdown of C1GALT1
decreased cell growth, migration, and sphere formation of ES-2 and OVTW59-p4
cells. Conversely, overexpression of C1GALT1 promoted such malignant properties
of SKOV3 cells. Furthermore, C1GALT1 regulated the expression of several cancer
stemness-related genes, including CD133, CD24, Oct4, Nanog, and SNAI2, in ovarian
cancer cells. CONCLUSIONS: C1GALT1 modifies O-glycan expression and enhances
malignant behaviors in ovarian cancer cells, suggesting that C1GALT1 plays a role
in the pathogenesis of ovarian cancer and targeting C1GALT1 could be a promising
approach for ovarian cancer therapy.
PMID- 28498249
TI - Clinicopathological Characteristics and Prognostic Factors of Synchronous
Endometrial and Ovarian Cancers-A Single-Institute Review of 43 Cases.
AB - OBJECTIVES: The objectives of our study were to demonstrate the
clinicopathological characteristics and determine the prognostic factors for
women with synchronous primary cancers of the endometrium and ovary. METHODS: A
retrospective analysis of 43 pathologically proven cases of synchronous primary
endometrial and ovarian cancers diagnosed between January 2005 and December 2015
was carried out. Patients with uterine sarcomas, carcinosarcomas, borderline
tumors, and nonepithelial tumors of the ovary and patients who received
neoadjuvant chemotherapy were excluded from the study. Disease-free survival
(DFS) and overall survival (OS) rates were calculated using the Kaplan-Meier
method. Multivariate analysis to determine independent prognostic factors was
performed using the Cox regression model. RESULTS: Mean age at diagnosis was
48.49 years. The most common presenting symptom was abnormal uterine bleeding in
58.2% of the patients. Nineteen patients (44.2%) were obese, and 13 patients
(30.2%) were overweight. Twelve patients (30%) were nulliparous, and 25 (58.2%)
were premenopausal; 76.7% of the patients received adjuvant treatment after
surgery. Mean follow-up period was 48.9 months. Twelve patients developed
recurrence, and 7 patients died of recurrent disease. The 5-year DFS for all
patients was 65.13%, and the 5-year OS was 79.75%. The 118-month DFS and 118
month OS were 65.13% and 72.50%, respectively. On multivariate analysis, grade 3
disease for both endometrial and ovarian cancers and presence of lymphovascular
space invasion were associated with significantly worse 118-month DFS and OS,
respectively. CONCLUSIONS: Women with synchronous primary endometrial and ovarian
cancers are young, nulliparous, obese, and premenopausal and have a favorable
overall prognosis. Grade 3 disease at both sites and presence of lymphovascular
space invasion are independent prognostic factors for recurrence and survival,
respectively.
PMID- 28498250
TI - Prediction of Site-Specific Tumor Relapses in Patients With Stage I-II
Endometrioid Endometrial Cancer.
AB - OBJECTIVE: The aim of this study was to investigate the association of predictors
of an advanced disease and/or poor outcome with the occurrence of tumor relapses
in different anatomical sites in patients with stage I-II endometrioid
endometrial cancer. METHODS: A total of 929 patients were included in the study.
The median follow-up time was 57 months (range, 1-108 months). The studied
variables were: poor tumor differentiation, myometrial invasion 50% or greater,
tumor size 3 cm or greater, lymphovascular space invasion, cervical stromal
invasion, positive peritoneal cytology, old age (>77 years), obesity (body mass
index >=30 kg/m), and diabetes. RESULTS: A relapse was diagnosed in 98 patients
(10.5%) (vaginal in 15, pelvic in 27, intra-abdominal beyond the pelvis in 27,
extra-abdominal in 29). None of the variables were associated with an altered
risk of vaginal or pelvic relapses in univariate analyses. Poor differentiation,
myometrial invasion 50% or greater, tumor size 3 cm or greater, and positive
peritoneal cytology were associated with an increased risk of intra-abdominal
relapses beyond the pelvis (odds ratios [ORs] between 2.2 and 9.6). With the
exception of obesity and diabetes, all variables were associated with an
increased risk of extra-abdominal relapses (ORs between 2.3 and 13). Tumor size 3
cm or greater (OR, 3.1) and positive peritoneal cytology (OR, 16) predicted intra
abdominal relapses beyond the pelvis in multivariate analysis, whereas poor
differentiation (OR, 2.9), myometrial invasion 50% or greater (OR, 4.0), and
positive peritoneal cytology (OR, 27) predicted extra-abdominal relapses.
Compared with vaginal relapses, intra-abdominal relapses beyond the pelvis and
extra-abdominal relapses were associated with a worse disease-specific survival.
Survival of patients with a pelvic relapse did not differ from that of patients
with a vaginal relapse. CONCLUSIONS: Risk variables of endometrial cancer are
differently associated with relapses in different locations. Our findings may
promote studies that explore the most efficient adjuvant therapy in high-risk
early-stage endometrioid endometrial cancer.
PMID- 28498251
TI - Undiagnosed Uterine Sarcomas Identified During Surgery for Presumed Leiomyoma at
a National Tertiary Hospital in Thailand: A 10-Year Review.
AB - OBJECTIVES: The aim of this study was to evaluate the rate, clinical
characteristics, and survival outcomes of an undiagnosed uterine malignancy in
patients who underwent surgical treatment for presumed leiomyomas. METHODS:
Medical records of patients who underwent surgical treatment for presumed
leiomyomas, from January 2004 to September 2013, were retrospectively reviewed,
and the data were followed until September 2016. Demographic data, tumor
characteristics, oncologic treatment, and response rate were analyzed by
descriptive statistics. Kaplan-Meier method was used for survival analysis. This
study includes follow-up data through December 31, 2016. RESULTS: A total of
11,258 medical records of presumed leiomyoma patients undergoing hysterectomy
during the studied period were reviewed. Pathology of uterine sarcoma was found
in 22 patients (0.2%), all of whom were included. Nineteen patients had
leiomyosarcoma, and 3 had endometrial stromal sarcoma. Mean age of patients was
48.3 +/- 6.9 years. All patients underwent total abdominal hysterectomy, with 20
patients undergoing concurrent bilateral salpingo-oophorectomy. Uterine sarcoma
was classified as stage IB in 21 patients and stage IIIC in 1 patient. Fifteen
patients were prescribed the following adjuvant treatment: chemotherapy in 13
patients and megestrol acetate in 2 patients. Thirteen patients had recurrent
disease, and 3 patients died of their disease. The mean progression-free survival
was 50.1 +/- 41.3 months, and overall survival was 59.3 +/- 43.0 months.
CONCLUSIONS: One in 512 patients who underwent hysterectomy because of presumed
uterine leiomyomas had inadvertent uterine sarcomas. Even with adjuvant therapy,
treatment outcome was rather poor, with almost 60% recurrence rate and median
progression-free survival and overall survival of less than 5 years.
PMID- 28498252
TI - Completing or Abandoning Radical Hysterectomy in Early-Stage Lymph Node-Positive
Cervical Cancer: Impact on Disease-Free Survival and Treatment-Related Toxicity.
AB - INTRODUCTION: Management regarding completing hysterectomy in case of
intraoperative finding of positive lymph nodes in early-stage cervical cancer
differs between institutions. The aim of this study was to compare survival and
toxicity after completed hysterectomy followed by adjuvant (chemo-)radiotherapy
versus abandoned hysterectomy and primary treatment with chemoradiotherapy (CRT).
METHODS: A retrospective multicenter cohort study was performed. All patients
were scheduled for radical hysterectomy with pelvic lymphadenectomy (RHL). In the
RHL group, hysterectomy was completed followed by adjuvant (chemo-)radiotherapy.
In the second group, hysterectomy was abandoned, and CRT was conducted. Primary
outcomes were disease-free survival (DFS) and overall survival. A multivariable
analysis on DFS was performed. Toxicity was scored according to the National
Cancer Institute CTCAE (Common Terminology Criteria for Adverse Events) v4.03.
RESULTS: A total of 121 patients were included (RHL, n = 89; CRT, n = 32). There
was no difference in overall survival (84% vs 77%). Five-year DFS was in favor of
completing RHL (81% vs 67%). Multivariable analysis showed that, corrected for
lymph node variables, treatment regimen was not associated with DFS. After RHL,
pelvic recurrence rate was significantly lower compared with CRT (2% vs 16%).
CTCAE grade 3-4 toxicity rates were higher in the CRT compared with the RHL group
(59% vs 30%), mainly because of differences in chemotherapy-related hematologic
toxicity. CONCLUSIONS: In patients with clinically N0 early-stage cervical cancer
with intraoperative detection of positive nodes, completing RHL followed by
adjuvant (chemo-)radiotherapy may result in a better pelvic control compared with
abandoning hysterectomy and treatment with chemoradiotherapy. However, if
corrected for lymph node variables, treatment (RHL or CRT) was not associated
with DFS.
PMID- 28498253
TI - Targeting Foxm1 Improves Cytotoxicity of Paclitaxel and Cisplatinum in Platinum
Resistant Ovarian Cancer.
AB - OBJECTIVE: Aberrantly activated FOXM1 (forkhead box protein M1) leading to
uncontrolled cell proliferation and dysregulation of FOXM1 transcription network
occurs in 84% of ovarian cancer cases. It was demonstrated that thiostrepton, a
thiazole antibiotic, decreases FOXM1 expression. We aimed to determine if
targeting the FOXM1 pathway with thiostrepton could improve the efficacy of
paclitaxel and cisplatin in human ovarian cancer ascites cells ex vivo. METHODS:
Human ovarian cancer cell lines and patients' ascites cells were treated with
paclitaxel, cisplatin, and thiostrepton or a combination for 48 hours, and
cytotoxicity was assessed. Drug combination effects were determined by
calculating the combination index values using the Chou and Talalay method.
Quantitative real-time polymerase chain reaction was performed to determine
changes in FOXM1 expression and its downstream targets. RESULTS: Ovarian cancer
cell lines and the patients' ascites cancer cells had an overexpression of FOXM1
expression levels. Targeting FOXM1 with thiostrepton decreased FOXM1 mRNA
expression and its downstream targets such as CCNB1, CDC25B, leading to cell
death in both cell lines and patients' ascites cancer cells. Furthermore,
addition of thiostrepton to paclitaxel and cisplatin showed synergistic effects
in chemoresistant ovarian cancer patients' ascites cells ex vivo. CONCLUSION:
Targeting FOXM1 may lead to novel therapeutics for chemoresistant epithelial
ovarian cancer.
PMID- 28498254
TI - A Novel Prediction Model for Postmolar Gestational Trophoblastic Neoplasia and
Comparison With Existing Models.
AB - OBJECTIVE: The aim of this study was to comparatively study a novel model and
existing models of predicting postmolar gestational trophoblastic neoplasia
(GTN). METHODS: Two hundred twenty-two patients with complete hydatidiform moles
were enrolled retrospectively. A natural regression was noted in 195 patients
(spontaneous regression group), whereas the remaining 27 patients entered
postmolar GTN (postmolar GTN group). The upper limits of the 95% confidence
interval of human chorionic gonadotropin (hCG) values and hCG regression rates
were calculated aggregately from the spontaneous regression group. The 4
prediction models (weekly hCG regression curve and weekly hCG regression rate
curve reported by previous studies; daily hCG regression curve and daily hCG
regression rate curve pioneered by us) were then plotted. The individual hCG
curve of the postmolar GTN group was plotted and compared with the prediction
models, respectively. The individual hCG curve superimposing the prediction curve
was considered showing an elevated risk of GTN. RESULTS: All patients with
postmolar GTN were preidentified by daily hCG regression rate curve. The other 3
prediction models had a considerable rate of failure in identification. Mean
diagnosis time of daily hCG regression rate curve was significantly lower (P =
0.008), with an average of 15.3 days gained compared with International
Federation of Gynecology and Obstetrics criteria. Cochran Q test showed that
daily hCG regression rate curve produced a significantly better performance in
predicting postmolar GTN than weekly hCG regression curve (P = 0.01).
CONCLUSIONS: Our data showed that daily hCG regression rate curve gives a better
prediction of postmolar GTN and might potentially enhance the monitoring of
patients with molar pregnancy, especially those who could not adhere to
International Federation of Gynecology and Obstetrics protocols. However, this
preliminary research should not change current clinical practice until further
validation is carried out.
PMID- 28498255
TI - The Significance of VSIG4 Expression in Ovarian Cancer.
AB - OBJECTIVES: The protein V-set and Ig domain-containing 4 (VSIG4), a novel B7
family-related macrophage protein with the capacity to inhibit T-cell activation,
has a potential role in cancer. Here we suggest its possibility as a therapeutic
target and prognostic biomarker of ovarian cancer. METHODS: Between January 2011
and June 2015, tumor tissues and peripheral blood samples were obtained during
surgery from 10 patients with benign ovarian tumors and 22 patients with ovarian
cancers. Messenger RNA and protein expression levels of VSIG4 in benign tumor and
cancer tissues were examined by the reverse transcription polymerase chain
reaction and Western blot, respectively. Soluble VSIG4 concentrations were
measured by an enzyme-linked immunosorbent assay. The correlation between VSIG4
expression and the prognosis of ovarian cancer was analyzed according to the
patients' clinicopathologic characteristics. RESULTS: VSIG4 messenger RNA and
protein expression levels in ovarian cancer tissues were higher than those in
benign ovarian tumors (P = 0.0013 and 0.0001, respectively). Soluble VSIG4
concentrations were increased in patients with ovarian cancer compared with that
in patients with benign ovarian tumors (P = 0.0452). Moreover, soluble VSIG4
levels were significantly increased in advanced-stage and recurrent ovarian
cancer (P = 0.0244 and 0.0288, respectively). High VSIG4 expression of cancer
tissue and low VSIG4 expression of plasma (soluble VSIG4) were associated with a
longer disease-free interval (P = 0.0246 and 0.0398, respectively). CONCLUSIONS:
VSIG4 is overexpressed in ovarian cancers compared with that in benign tumors.
This finding supports VSIG4 being used as a potential therapeutic target for
ovarian cancer. Furthermore, soluble VSIG4 levels are associated with the
progression and recurrence of ovarian cancer, indicating that soluble VSIG4 may
be used as a potential biomarker for predicting tumor prognosis.
PMID- 28498257
TI - The Addition of Adjuvant Chemotherapy to Radiation in Early-Stage High-Risk
Endometrial Cancer: Survival Outcomes and Patterns of Care.
AB - OBJECTIVE: Early-stage high-risk endometrial cancer (HREC) treated with adjuvant
radiotherapy (aRT) alone has been associated with an increased risk of distant
relapse. The addition of chemotherapy to radiotherapy (aCRT) may benefit overall
survival (OS). We investigated the patterns-of-care and OS benefit of aCRT in
HREC by analyzing a large national registry. METHODS: Our query was limited to
patients with the International Federation of Gynecology and Obstetrics stage IB
and II HREC with either papillary serous, clear cell, or grade 3 adenocarcinoma,
diagnosed between 2004 and 2012. Logistic and Cox regression analyses were
utilized to identify predictors of aCRT use and OS, respectively. Survival
analysis was performed with Kaplan Meier and log-rank methods. Propensity score
matching was employed to decrease the potential influence of selection bias.
RESULTS: A total of 11,746 patients were identified for analysis with 8206
(69.9%) receiving aCRT, and 3540 (30.1%) received aRT. Predictors of aCRT
included International Federation of Gynecology and Obstetrics stage II (odds
ratio [OR], 1.39; 95% confidence interval [CI], 1.22-1.57), papillary serous (OR,
9.44; 95% CI, 8.22-10.85) or clear cell (OR, 3.21; 95% CI, 2.59-3.97) histology,
lymph nodes removed (OR, 1.48; 95% CI, 1.31-1.69), and receipt of brachytherapy
alone (OR, 1.55; 95% CI, 1.36-1.78). Estimated 5-year OS was 75.2% for patients
receiving aRT only and 79.2% for those receiving aCRT (P < 0.001). When compared
with aRT, aCRT was associated with improved OS on multivariate (hazard ratio,
0.78; 95% CI, 0.61-0.99) analysis. A univariate shared-frailty Cox regression
after propensity score matching revealed persistence of the OS benefit with aCRT
(hazard ratio, 0.74; 95% CI, 0.65-0.84). CONCLUSIONS: The addition of adjuvant
chemotherapy to radiation in HREC is associated with improved OS. Multiple
demographic and clinical factors significantly influence the choice of adjuvant
therapy in this setting.
PMID- 28498256
TI - Paragon (ANZGOG-0903): Phase 2 Study of Anastrozole in Women With Estrogen or
Progesterone Receptor-Positive Platinum-Resistant or -Refractory Recurrent
Ovarian Cancer.
AB - BACKGROUND: There is some evidence that a subset of patients with recurrent
ovarian cancer may benefit from antiestrogen therapy. The Paragon study is a
basket protocol that includes a series of phase 2 trials investigating the
activity of anastrozole in patients with estrogen or progesterone receptor
positive recurrent gynecological cancers. We report the results of treatment in
patients with platinum-resistant or -refractory recurrent epithelial ovarian
cancer. METHODS: Postmenopausal women who had estrogen and/or progesterone
receptor-positive platinum-resistant or platinum-refractory recurrent ovarian
cancer and disease measurable by Response Evaluation Criteria In Solid Tumors
(RECIST) version 1.1 or GCIG (Gynecologic Cancer InterGroup) CA-125 criteria were
eligible. Patients received anastrozole 1 mg daily until progression or
unacceptable toxicity. The study was prospectively registered
(ACTRN12610000796088). RESULTS: There were 49 evaluable patients, and clinical
benefit was observed in 13 (27%; 95% confidence interval [CI], 16%-40%). There
were no complete or partial RECIST version 1.1 responses. Clinical benefit was
associated with higher global quality-of-life scores. Median progression-free
survival was 2.7 months (95% CI, 2.0-2.8 months). The median duration of clinical
benefit was 2.8 months (95% CI, 2.6-5.7 months). Most patients (83%) progressed
within 6 months. Seven patients continued on treatment for longer than 6 months.
Anastrozole was well tolerated in most patients. Subgroup analysis suggested
greater clinical benefit in patients with tumors with estrogen-receptor
histoscore of more than 200, but this difference was not statistically
significant. CONCLUSIONS: A subset of patients with estrogen- or progesterone
positive platinum-resistant or platinum-refractory recurrent epithelial ovarian
cancers derives clinical benefit from anastrozole, with acceptable toxicity. The
challenge remains how to identify them.
PMID- 28498258
TI - Evaluation and Selection of Quality Indicators for the Management of Endometrial
Cancer.
AB - OBJECTIVE: The aim of this study was to evaluate 36 quality indicators (QIs) for
monitoring the quality of care of uterine cancer to be implemented in the EFFECT
(effectiveness of endometrial cancer treatment) project. METHODS: The 36 QIs were
evaluated in the first 10 patients diagnosed with endometrial cancer and managed
in 14 French hospitals in 2011. To assess the status of each QI, a questionnaire
detailing the 36 QIs was sent to each hospital, and the information was cross
checked with information from the multidisciplinary staff meeting, surgical
reports, and pathological reports. The QIs were evaluated in terms of
measurability and improvability. The remaining QIs were evaluated with a multiple
correspondence analysis to highlight the interrelationships between qualitative
variables describing a population. RESULTS: Thirteen of the 14 institutions
responded to the survey for a total of 130 patients. Twenty-five of the 36 QIs
affected less than 80% of the patients. Thirteen QIs were found not to be
improvable because they reached more than 95% of the theoretical target. Finally,
5 QIs concerning more than 80% of the patients were found to be improvable. The
multiple correspondence analysis finally identified 3 dimensions-outcome, safety,
and perioperative management-that included the 5 QIs. CONCLUSIONS: In the present
study, 5 of the 36 QIs suggested by the EFFECT project seem to be sufficient to
report on the quality of endometrial cancer management. Further studies are
needed to correlate the information provided by those 5 questions and the
relevant outcomes reflecting quality of care in endometrial cancer.
PMID- 28498259
TI - Efficacy of Pegylated Liposomal Doxorubicin in Low-Grade Serous Ovarian
Carcinoma.
AB - OBJECTIVE: The aim of this study was to assess the efficacy of pegylated
liposomal doxorubicin (PLD) in low-grade serous ovarian carcinoma (LGSOC).
METHODS: We retrospectively identified patients with LGSOC who were treated with
PLD. Response to therapy was evaluated by RECIST 1.1 criteria. Progression-free
survival (PFS) and overall survival were calculated. In addition, PFS on PLD was
compared with the patient's most recent PFS on previous therapy. RESULTS: Twenty
four patients were treated with PLD. Three patients were not evaluable, leaving
21 patients evaluable for response. Pegylated liposomal doxorubicin was dosed at
40 mg/M every 28 days except in 7 patients (5 received PLD dosed at 30 mg/M in
combination with carboplatin and 2 received PLD dosed at 20 mg/M, one of which
was in combination with etoposide). Four of the patients who received PLD in
combination subsequently received PLD alone for 4+, 12, 21, and 29 cycles,
respectively. Three patients (14.3%) had a complete response and remained
progression free at 8, 31, and 34 months, respectively. Two of these patients
received PLD alone. The third complete response patient initially received PLD in
combination with carboplatin and then went on to receive PLD alone during which a
complete radiologic response was achieved. No difference in response or PFS by
platinum sensitivity was noted (Ps = 0.73 and 0.62, respectively). Fourteen
patients had stable disease for a median of 18 months. Among the 14 patients with
stable disease, the PFS on PLD exceeded the previous PFS in 11 patients (78.6%)
from 1.3 to 20.6 folds, with a median of 3.5 folds. The 2 of the 3 lowest
increases in PFSs were seen in patients whose therapy was terminated despite
stable disease. CONCLUSIONS: Pegylated liposomal doxorubicin is relatively active
in LGSOC. The treatment of stable disease resulted in increase in PFS in 78.6% of
patients by a mean of 350%.
PMID- 28498260
TI - Combined Gene Therapy Using AdsVEGFR2 and AdsTie2 With Chemotherapy Reduces the
Growth of Human Ovarian Cancer and Formation of Ascites in Mice.
AB - OBJECTIVES: Ovarian cancer is highly dependent on tumor microvessels and
angiogenesis regulated by vascular endothelial growth factors (VEGFs) and their
receptors (VEGFRs) and angiopoietins (Ang) and their Tie receptors. We studied
the efficacy of adenoviral (Ad) gene therapy with soluble VEGFR2 and Tie2
combined with paclitaxel and carboplatin for the treatment of ovarian cancer.
METHODS: An intraperitoneal human ovarian cancer xenograft model in nude mice (n
= 44) was used in this study. Gene therapy was given intravenously when the
presence of sizable tumors was confirmed in magnetic resonance imaging. The study
groups were as follows: AdCMV as a control (group I), AdCMV with chemotherapy
(group II), AdsVEGFR2 and AdsTie2 (group III), and AdsVEGFR2 and AdsTie2 with
chemotherapy (group IV). Antitumor effectiveness was assessed by overall tumor
growth, ascites, immunohistochemistry, microvessel density, and sequential
magnetic resonance imaging analyses. RESULTS: AdsVEGFR2 and AdsTie2 gene therapy
(group III) significantly reduced tumor weights as compared with group II (P =
0.007). Accumulation of ascites was significantly reduced when the mice were
treated with AdsVEGFR2 and AdsTie2 gene therapy or with combined gene therapy and
chemotherapy as compared with controls (P = 0.029 and P = 0.010, respectively).
Vascular endothelial growth factor and Ang2 levels in ascites fluid were elevated
after the gene therapy. CONCLUSIONS: Combined inhibition of VEGF/VEGFR2 and
Ang/Tie2 pathways provided efficient therapy for ovarian cancer in mice. In
addition, antiangiogenic gene therapy has potential as a treatment for the
accumulation of ascites.
PMID- 28498261
TI - Clear Cell Carcinoma of the Uterine Cervix: A Clinical and Pathological Analysis
of 47 Patients Without Intrauterine Diethylstilbestrol Exposure.
AB - OBJECTIVES: The aim of this study was to summarize the clinical and pathological
characteristics and to conduct prognosis analysis of patients who were diagnosed
with clear cell carcinoma of the uterine cervix (CCCUC) and without a history of
exposure to diethylstilbestrol. METHODS: We performed a retrospective review of
all the patients with CCCUC who were diagnosed and treated at Zhejiang Cancer
Hospital between 1998 and 2014. Charts were reviewed for clinical and
pathological characteristics, and prognosis analysis was conducted. RESULTS: A
total of 47 patients were included. Median age was 52 years. No patient had a
history of exposure to diethylstilbestrol. The International Federation of
Gynecology and Obstetrics stage distribution was 55.3% (n = 26) stage I, 40.4% (n
= 19) stage II, 2.1% (n = 1) stage III, and 2.1% (n = 1) stage IV. Forty-two
patients (89.4%) underwent radical hysterectomy and pelvic lymphadenectomy.
Pathological examination revealed deep cervical stromal invasion (greater than
two thirds) in 20 patients (48.4%), pelvic lymph node (PLN) metastasis in 10
patients (23.8%), lymphovascular space involvement in 9 patients (21.4%), and
ovarian metastasis in 1 patient (2.4%). Advanced tumor stage (IIB-IV), larger
tumor size (>4 cm), and PLN metastasis had negative effects on progression-free
survival (PFS) and overall survival (OS) (P < 0.05). Adjuvant radiation therapy
alone or concurrent chemoradiation therapy after radical surgery did not affect
PFS or OS in patients with risk factors (P > 0.05). CONCLUSIONS: International
Federation of Gynecology and Obstetrics stage, tumor size, and PLN status were
prognostic factors for both PFS and OS in patients with CCCUC. The long-term
effects of adjuvant radiation therapy or concurrent chemoradiation therapy may be
limited for CCCUC patients with risk factors. Future larger case series or
clinical trials are required to confirm these findings.
PMID- 28498262
TI - Sarcoma Risk in Uterine Surgery in a Tertiary University Hospital in Germany.
AB - OBJECTIVES: There is a risk to incidentally spread uterine malignancies,
especially sarcoma, if tissue is morcellated during hysterectomy or myoma
enucleation. In the last years, a worldwide discussion has been started about
this problem. However, the risk seems to be very small in recent studies. This
study aims at further investigating the risk of disseminating uterine malignancy
during uterine surgery in a tertiary university hospital in Germany. METHODS: In
a retrospective setting, all cases of uterine myometrial surgery (hysterectomies
and myomectomies) in our clinic during a period of 10 years were identified using
clinical databases. Histology was linked and searched for uterine malignancies.
All cases were reviewed for incidental morcellation of malignant tissue. RESULTS:
Between 2004 and 2014, we identified 2825 cases of uterine myometrial surgery.
Morcellating procedures were used in 20% of the 1402 hysterectomy procedures
(280/1402) and in 13.7% of the 1423 fibroid removals (195/1423). We identified 23
uterine mesenchymal malignancies (sarcoma, n = 10; carcinosarcoma, n = 13). In 3
cases, there was no evidence or sign of a malignant disease preoperatively in a
procedure with a morcellation (vaginal hysterectomy with morcellation, n = 1;
open fibroid enucleation, n = 2). CONCLUSIONS: A small risk (0.35% [1/280]) of
accidental morcellation during hysterectomy with morcellation was found in our
study. We did not observe an occult case of sarcoma after myomectomy with
morcellation (0/195), but we found 2 cases of accidental sarcoma after myomectomy
without morcellation. For these reasons, minimally invasive surgery with
morcellation should not be excluded a priori. The patient should be well informed
about the risks and various options. The advantage of laparoscopic surgery should
be balanced against the risk of the unknown spread of malignant tissue.
PMID- 28498264
TI - Defining the Hook Region Anatomy of the Guinea Pig Cochlea for Modeling of Inner
Ear Surgery.
AB - HYPOTHESIS: The aim of this study was to describe the hook region anatomy of the
guinea pig cochlea to identify the optimal surgical approach for cochlear
implantation and to determine what anatomical structures are at risk. BACKGROUND:
Animal studies investigating hearing loss after cochlear implantation surgery are
currently constrained by the lack of a reproducible implantation model. METHODS:
Guinea pig cochleae were imaged using thin-sheet laser imaging microscopy. Images
were stitched, reconstructed, and segmented for analysis. Insertion vectors were
determined by tracing their paths to the outer wall and converting to Cartesian
coordinates. Spherical surface and multiplane views were generated to analyze
outer wall and radial forces of the insertion vector. RESULTS: Thin-sheet laser
imaging microscopy enabled quantitative, whole specimen analysis of the soft and
bony tissue relationships of the complex cochlear hook region in any desired
plane without loss of image quality. Round window or cochleostomy approaches in
the anteroinferior plane avoided direct damage to cochlear structures.
Cochleostomy approach had large interindividual variability of angular depth and
outer wall forces but predictable radial force. CONCLUSION: The guinea pig hook
region and lower basal turn have similar structural relationships to humans.
Careful cochleostomy placement is essentially for minimizing cochlear trauma and
for ensuring a straight insertion vector that successfully advances around the
outer wall. Experiments with guinea pigs that control for the surgical approach
are likely to provide useful insights into the aetiology and the development of
therapies directed at postimplantation hearing loss.
PMID- 28498263
TI - Cochlear Implantation in Patients With Usher Syndrome Type IIa Increases
Performance and Quality of Life.
AB - OBJECTIVES: Usher syndrome type IIa (USH2a) is characterized by congenital
moderate to severe hearing impairment and retinitis pigmentosa. Hearing
rehabilitation starts in early childhood with the application of hearing aids. In
some patients with USH2a, severe progression of hearing impairment leads to
insufficient speech intelligibility with hearing aids and issues with adequate
communication and safety. Cochlear implantation (CI) is the next step in
rehabilitation of such patients. This study evaluates the performance and benefit
of CI in patients with USH2a. DESIGN: Retrospective case-control study to
evaluate the performance and benefit of CI in 16 postlingually deaf adults (eight
patients with USH2a and eight matched controls). Performance and benefit were
evaluated by a speech intelligibility test and three quality-of-life
questionnaires. RESULTS: Patients with USH2a with a mean age of 59 years at
implantation exhibited good performance after CI. The phoneme scores improved
significantly from 41 to 87% in patients with USH2a (p = 0.02) and from 30 to 86%
in the control group (p = 0.001). The results of the questionnaire survey
demonstrated a clear benefit from CI. There were no differences in performance or
benefit between patients with USH2a and control patients before and after CI.
CONCLUSIONS: CI increases speech intelligibility and improves quality of life in
patients with USH2a.
PMID- 28498265
TI - The Effect of Systemic Steroid on Hearing Preservation After Cochlear
Implantation via Round Window Approach: A Guinea Pig Model.
AB - HYPOTHESIS: When administered perioperatively, systemic dexamethasone will reduce
the hearing loss associated with cochlear implantation (CI) performed via the
round window approach. BACKGROUND: The benefits of electroacoustic stimulation
have led to interest in pharmacological interventions to preserve hearing after
CI. METHODS: Thirty guinea pigs were randomly divided into three experimental
groups: a control group; a 3-day infusion group; and a 7-day infusion group.
Dexamethasone was delivered via a mini-osmotic pump for either 3 or 7 days after
CI via the round window. Pure tone-evoked auditory brainstem response (ABR)
thresholds were monitored for a period of 12 weeks after CI. The cochleae were
then collected for histology. RESULTS: At 4 and 12 weeks after CI, ABR threshold
shifts were significantly reduced in both 7-day and 3-day infusion groups
compared with the control group. Furthermore, the 7-day infusion group has
significantly reduced ABR threshold shifts compared with the 3-day infusion
group. The total tissue response, including fibrosis and ossification, was
significantly reduced in the 7-day infusion group compared with the control
group. On multiple regression the extent of fibrosis predicted hearing loss
across most frequencies, while hair cell counts predicted ABR thresholds at 32
kHz. CONCLUSION: Hearing protection after systemic administration of steroids is
more effective when continued for at least a week after CI. Similarly, this
treatment approach was more effective in reducing the fibrosis that encapsulates
the CI electrode. Reduced fibrosis seemed to be the most likely explanation for
the hearing protection.
PMID- 28498266
TI - Use of Positive Airway Pressure Following Middle Ear Surgery: A Practice Survey
of Otologists.
AB - BACKGROUND: Positive airway pressure (PAP) devices are used as treatment for
obstructive sleep apnea (OSA). PAP may increase middle ear pressure which is of
interest to otologic surgeons. There is a lack of data to guide management of PAP
therapy after middle ear surgery. OBJECTIVE: To elucidate how otologic surgeons
manage PAP in their patients after ear surgery. STUDY DESIGN: A survey e-mailed
to practicing members of the American Neurotology Society. RESULTS: Among 60
respondents, the most common recommendations to patients were to avoid PAP use
for 1 week (40%), return to normal use immediately (23.3%), avoid PAP for 1 month
(13.3%), or avoid PAP for 1 day (13.3%) after surgery. Twenty percent of
providers reported that they change their advice on the basis of the PAP pressure
settings (i.e., shorter hiatus for higher settings). Among respondents, 47% think
that they have patients with middle ear issues because of PAP and 13% attributed
surgical failures to PAP use. One-third of providers routinely pack the
Eustachian tube during surgery. Providers who attributed a negative surgical
outcome to PAP use were more likely to routinely pack/plug the Eustachian tube
during otologic surgery (p = 0.001). CONCLUSION: Treatment recommendations
regarding postoperative PAP treatment for obstructive sleep apnea vary greatly
among practicing otologists. Providers who think that an adverse outcome was
attributed to PAP use were more likely to prophylactically plug the Eustachian
tube during surgery. Future research will provide additional information which
will allow a better understanding of the effect of PAP on the middle ear,
especially after otologic surgery.
PMID- 28498267
TI - Endoscopic Infracochlear Approach for Drainage of Petrous Apex Cholesterol
Granulomas: A Case Series.
AB - OBJECTIVE: To describe the feasibility and technical nuances of a transcanal
endoscopic infracochlear approach for drainage of petrous apex cholesterol
granulomas. STUDY DESIGN: Retrospective case review. SETTING: Tertiary care
university hospital. PATIENTS: A 32-year-old man with bilateral petrous apex
cholesterol granulomas and a 54-year-old man with a left-sided petrous apex
granuloma each with symptoms necessitating surgical intervention. INTERVENTIONS:
Transcanal endoscopic infracochlear approach for drainage of the cholesterol
granulomas. MAIN OUTCOME MEASURES: Operation efficacy, corridor size, and
perioperative morbidity. RESULTS: All three cholesterol granulomas were
successful drained without violating the cochlea, jugular bulb, or carotid
artery. The dimensions of the infracochlear surgical corridor measured 5 mm * 6
mm, 3.5 mm * 3.5 mm, and 6 mm * 4 mm, respectively. All corridors facilitated
visualization within the cyst and allowed lyses of adhesions for additional cyst
content eradication. All patients had resolution of their acute symptoms. Two of
the three subjects had serviceable hearing before and after their procedures. One
patient required revision surgery 2-months after their initial procedure
secondary to recurrent symptoms from acute hemorrhage within the cyst cavity. The
infracochlear tract in this patient was noted to be patent. CONCLUSIONS: A
transcanal endoscopic infracochlear approach is feasible for the management of
cholesterol granuloma. The surgical access was wide enough to introduce the
endoscope into the petrous apex cavity in each case. Further studies are needed
to compare the efficacy and perioperative morbidity versus the traditional
postauricular transtemporal approaches.
PMID- 28498268
TI - Transcanal Endoscopic Ear Surgery for Excision of a Facial Nerve Venous
Malformation With Interposition Nerve Grafting: A Case Report.
AB - OBJECTIVE: To illustrate a novel approach for the surgical management of a venous
malformation of the facial nerve, including interposition nerve grafting, via an
exclusively transcanal endoscopic ear surgery (TEES) approach. PATIENT: Thirty
nine-year-old woman with a preoperative House-Brackmann (HB) grade IV facial
paresis secondary to a facial nerve tumor. INTERVENTION(S): Surgical excision and
interposition nerve graft via a transcanal endoscopic approach. MAIN OUTCOME
MEASURE(S): Completeness of resection, approach morbidities, and facial nerve
outcome. RESULTS: The TEES approach provided wide exposure of the facial nerve
from the geniculate ganglion through the mastoid segment. This visualization
facilitated gross total tumor resection, incus interposition ossicular
reconstruction, and placement of an interposition nerve graft. The nerve graft
was positioned in the fallopian canal and was secured at both ends with surgicel.
The patient had no postoperative complications. At 11-month follow-up her facial
function had returned to HB grade IV. CONCLUSIONS: This is the first report of
resecting a venous malformation of the facial nerve with concomitant
interposition nerve graft reconstruction via an exclusively endoscopic approach.
This report adds to the growing body of evidence that TEES can manage diverse
middle ear and lateral skull base pathology. Additional studies are needed to
fully elucidate the risk-benefit profile of this technique.
PMID- 28498269
TI - Real-Time Intracochlear Electrocochleography Obtained Directly Through a Cochlear
Implant.
AB - HYPOTHESIS: Utilizing the cochlear implant to record electrophysiologic responses
during device placement is a feasible and efficacious technique for monitoring
near real-time cochlear physiology during and following electrode insertion.
BACKGROUND: Minimizing intracochlear trauma during cochlear implantation has
emerged as a highly researched area to help improve patient performance.
Currently, conventional cochlear implant technology allows for the recording of
electrically evoked compound action potentials (eCAPs). Acoustically evoked
potentials may be more sensitive in detecting physiologic changes occurring as a
result of electrode insertion. Electrocochleography obtained from within the
cochlea allows hair cell and neural response monitoring along the cochlear spiral
at locations where changes most likely would occur. METHODS: Intracochlear
electrocochleography (ECochG) was recorded from the cochlear implant during
surgery in 14 subjects. A long acquisition time (54.5 ms), capable of measuring
potentials from the low frequency-serving apical region of the cochlea (125 and
500 Hz) was employed. Two distinct intracochlear processing methods were used and
compared in obtaining electrophysiologic data. RESULTS: Measureable intracochlear
ECochG responses were obtained from all 14 participants. The 1st harmonic
distortions (cochlear microphonic and auditory nerve neurophonic) generally
increased steadily with electrode insertion. Electrode and frequency scan
following insertion revealed that response amplitude varied based on location of
recording electrode and frequency of stimulation. Exquisite sensitivity to
manipulation during round window muscle packing was demonstrated. CONCLUSION:
Intracochlear ECochG recorded from the electrode array of the cochlear implant is
a highly feasible technique that sheds light on cochlear micromechanics during
cochlear implant electrode placement.
PMID- 28498270
TI - Age-Related Increase in Blood Levels of Otolin-1 in Humans.
AB - OBJECTIVE: To test the hypothesis that age-related demineralization of otoconia
will result in an age-related increase in blood levels of otoconia matrix
protein, otolin-1. STUDY DESIGN: Cross-sectional observational clinical trial.
SETTING: Clinical research center. PATIENTS: Seventy nine men and women ranging
in age from 22 to 95 years old. INTERVENTIONS: Diagnostic. MAIN OUTCOME MEASURES:
Blood levels of otolin-1 in relation to age. RESULTS: Levels of otolin-1 of
subjects divided into four age groups (1: 20-30 [n = 20], 2: 50-65 [n = 20], 3:
66-80 [n = 20], 4: 81-95 [n = 19] years old) demonstrated an increasing trend
with age. The difference between otolin levels of groups 2 and 3, as well as, (p
= 0.04) and 2 and 4 (p = 0.031) were statistically significant, but there was no
significant difference between the two oldest groups. CONCLUSIONS: Otolin-1 blood
levels are significantly higher in patients older than 65 years of age. This is
consistent with previous scanning electron microscopy findings of age-related
otoconia degeneration and increased prevalence of benign paroxysmal positional
vertigo (BPPV) with age. Normative data provided here can serve as important
reference values against which levels from BPPV patients can be compared with
further evaluate otolin-1 as a circulatory biomarker for otoconia degeneration.
PMID- 28498271
TI - Epidemiology of Dizzy Patient Population in a Neurotology Clinic and Predictors
of Peripheral Etiology.
AB - OBJECTIVE: To compare the proportion of peripheral versus nonperipheral dizziness
etiologies among all patients, inclusive of those presenting primarily or as
referrals, to rank diagnoses in order of frequency, to determine whether or not
age and sex predict diagnosis, and to determine which subgroups tended to undergo
formal vestibular testing. STUDY DESIGN: Retrospective cohort. SETTING: Academic
neurotology clinic. PATIENTS: Age greater than 18 neurotology clinic patients
with the chief complaint of dizziness. INTERVENTION(S): None. MAIN OUTCOME
MEASURE(S): Age, sex, diagnosis, record of vestibular testing. RESULTS: Two
thousand seventy-nine patients were assigned 2,468 diagnoses, of which 57.7 and
42.3% were of peripheral and nonperipheral etiologies, respectively. The most
common diagnoses were Meniere's (23.0%), vestibular migraine (19.3%), benign
paroxysmal positional vertigo (BPPV) (19.1%), and central origin, nonmigraine
(16.4%). Peripheral diagnoses are more likely to be found in men than in women
(odds ratio [OR] 1.59). Peripheral diagnoses were most likely to be found in the
60 to 69 age group (OR 3.82). There was not a significant difference in rate of
vestibular testing between women and men. Among patients with two diagnoses, the
most common combinations were vestibular migraine and BPPV then vestibular
migraine and Meniere's. CONCLUSIONS: A large proportion of patients seen for the
chief complaint of dizziness in the neurotology clinic were found not to have a
peripheral etiology of their symptoms. These data challenge a prevalent dogma
that the most common causes of dizziness are peripheral: BPPV, vestibular
neuritis, and Meniere's disease. Age and sex are statistically significant
predictors of peripheral etiology of dizziness.
PMID- 28498272
TI - Paget's Disease of the Temporal Bone: A Single-Institution Contemporary Review of
27 Patients.
AB - OBJECTIVES: To report a contemporary review from a single-institution series on
Paget's disease of the temporal bone (PDTB). STUDY DESIGN: Retrospective chart
review of patients evaluated from 1998 to 2016. SETTING: Quaternary referral
center. PATIENTS: Patients with radiographically confirmed PDTB. MAIN OUTCOME
MEASURES: Clinical, audiological, and radiological features and management
strategies of PDTB. RESULTS: A total of 50 temporal bones in 27 patients (15 men)
were diagnosed with PDTB. Symptoms at presentation included hearing loss (n = 23,
85%), headache (n = 18, 67%), dizziness (n = 14, 52%), tinnitus (n = 5, 19%),
chronic otitis media (n = 2, 7%), hemifacial spasm without facial paralysis (n =
1, 4%), multiple cranial neuropathies (n = 1, 4%), and neoplastic transformation
(n = 1, 4%). Of the 23 ears with audiometric data available for review, 65%
exhibited sensorineural hearing loss, and 35% mixed hearing loss. Long-term
audiometric follow-up was available on two patients, both of whom demonstrated
hearing loss at a rate greater than would be expected for normal aging. Two
patients underwent successful cochlear implantation, achieving open-set speech
recognition. Radiographic features of temporal bone involvement are reviewed and
illustrated. CONCLUSION: This is the largest single-institution clinical series
examining patients with PDTB in the English literature. Variable patterns of
temporal bone involvement by Paget's disease are observed leading to a diverse
set of clinical symptoms, including slowly progressive hearing loss, tinnitus,
compressive cranial neuropathies, and benign or malignant tumorigenesis.
Involvement typically begins in the petrous apex and progresses laterally. Otic
capsule bone demineralization occurs late in the disease process. Cochlear
implantation appears to be an effective management strategy for patients with
severe-to-profound hearing loss.
PMID- 28498275
TI - Influence of Acute Multispecies and Multistrain Probiotic Supplementation on
Cardiovascular Function and Reactivity to Psychological Stress in Young Adults: A
Double-Blind, Randomized, Placebo-Controlled Trial.
AB - OBJECTIVE: The potential influence of probiotic supplementation on cardiovascular
health and stress responsivity remains largely unexplored. Some evidence suggests
the possibility that probiotics may influence blood pressure. A separate body of
research suggests that exaggerated cardiovascular reactions to acute
psychological stress in the laboratory predict cardiovascular morbidity and
mortality. The current investigation explored the effect of acute probiotic use
on (1) resting cardiovascular measures in healthy young adults and (2)
cardiovascular and psychological reactions to an acute psychological stressor in
the laboratory. METHOD: Participants (N = 105, M [SD] age = 20.17 [1.26], 84.8%
white) completed a 2-week, double-blind, and placebo-controlled trial of a
multispecies and multistrain probiotic. Exclusion criteria included previous
probiotic use, diagnosed gastrointestinal disorder, and/or current antibiotic
use. At visits 1 and 2, participants completed the Paced Auditory Serial Addition
Test, a widely used psychological stress task. Participants were randomly
assigned to a probiotic blend or matched placebo. RESULTS: Compared with placebo,
2-week probiotic supplementation did not affect resting measures of
cardiovascular function, cardiovascular responses during or recovery from stress,
or psychological reactions to acute psychological stress. CONCLUSIONS: Contrary
to expectations, short-term use of a probiotic supplement in healthy participants
did not influence measures of cardiovascular function or responsivity to
psychological stress. Future research is needed to determine species- and strain
specific effects of probiotics in healthy participants with various degrees of
stress responsiveness, as well as in diseased populations.
PMID- 28498274
TI - Fornix Structural Connectivity and Allostatic Load: Empirical Evidence From
Schizophrenia Patients and Healthy Controls.
AB - OBJECTIVE: The fornix is a white matter tract carrying the fibers connecting the
hippocampus and the hypothalamus, two essential stress-regulatory structures of
the brain. We tested the hypothesis that allostatic load (AL), derived from a
battery of peripheral biomarkers indexing the cumulative effects of stress, is
associated with abnormalities in brain white matter microstructure, especially
the fornix, and that higher AL may help explain the white matter abnormalities in
schizophrenia. METHODS: Using 13 predefined biomarkers, we tested AL in 44
schizophrenic patients and 33 healthy controls. Diffusion tensor imaging was used
to obtain fractional anisotropy (FA) values of the fornix and other white matter
tracts. RESULTS: AL scores were significantly elevated in patients compared with
controls (F(3,77) = 7.87, p = .006). AL was significantly and inversely
correlated with FA of fornix in both controls (r = -.58, p = .001) and patients
(r = -.36, p = .023). Several nominally significant (p < .05 but did not survive
Bonferroni correction for multiple comparison) correlations were also observed
between AL and FA of other white matter tracts in schizophrenic patients.
However, the fornix was the only tract exhibiting a correlation with AL in both
groups. CONCLUSIONS: These results provide initial evidence that allostatic
processes are linked to fornix microstructure in clinical participants.
PMID- 28498276
TI - Influence of Uncertain Anticipation on Brain Responses to Aversive Rectal
Distension in Patients With Irritable Bowel Syndrome.
AB - OBJECTIVE: We investigated whether certainty and uncertainty of impending
aversive visceral sensation differently modulate regional brain activity, both
during anticipation and visceral sensation in irritable bowel syndrome (IBS)
patients compared with healthy controls. METHODS: Twenty-six IBS patients (14
women) and 29 healthy controls (15 women) were enrolled in a functional magnetic
resonance imaging study. Participants received rectal distention at an
individually titrated severe discomfort level that was preceded by visual cues to
induce certain (100% chance of distention), uncertain (50% chance), and safe (0%
chance) anticipation. RESULTS: Subjective ratings of anticipatory fear before and
discomfort during distention were similar between IBS and control participants
under cued certainty and uncertainty (p > .05). Uncertain anticipation compared
with certain anticipation induced greater activation of anterior midcingulate
cortex, thalamus, and visual processing areas in IBS patients compared with
controls. Rectal distention after the uncertain, but not certain, cue induced
higher activity in the posterior- and midcingulate cortices and the precuneus in
IBS compared with controls. Controls exhibited bilateral insula activation during
the nondistention period after the uncertain cue compared with the safe cue. IBS
patients failed to produce this response, which was possibly due to elevated
bilateral insular responses during nondistention after the safe cue. Brain data
were significant at a voxel-level threshold of puncorrected value of less than
.005 combined with a cluster-level threshold of pFWE-corrected value of less than
.05. CONCLUSIONS: Preceding uncertainty differentially modulates the brain
processing of physiologically identical rectal stimulation in IBS patients. Cue
dependent alterations in brain responses may underlie hypervigilance to visceral
sensations in IBS patients.
PMID- 28498277
TI - Influence of Visceral Interoceptive Experience on the Brain's Response to Food
Images in Anorexia Nervosa.
AB - OBJECTIVE: The aim of the study was to determine how visceral sensations affect
responses to food stimuli in anorexia nervosa (AN). METHODS: Twenty weight
restored, unmedicated adolescent and young adult women with AN and twenty healthy
control participants completed an interoceptive attention task during which they
focused on sensations from the heart, stomach, and bladder and made ratings of
these sensations. They then underwent functional magnetic resonance imaging
scanning while viewing pictures of food and nonfood objects. Between-groups t
tests were employed to investigate group differences in the relationship between
interoceptive sensation ratings and brain hemodynamic response to food pictures
and, specifically, to highly palatable foods. RESULTS: In response to food
pictures, AN participants exhibited a positive relationship between stomach
sensation ratings and posterior insula activation (peak t = 4.30). AN
participants displayed negative relationships between stomach sensation ratings
and amygdala activation (peak t = -4.05) and heart sensation ratings and
ventromedial prefrontal cortex activation (peak t = -3.52). In response to highly
palatable foods, AN was associated with positive relationships between stomach
sensation ratings and activity in the subgenual anterior cingulate (peak t =
3.88) and amygdala (peak t = 4.83), and negative relationships in the ventral
pallidum (peak t = -3.99) and ventral tegmental area (peak t = -4.03). AN
participants also exhibited negative relationships between cardiac sensations and
activation in response to highly palatable foods in the putamen (peak t = -3.41)
and ventromedial prefrontal cortex (peak t = -3.61). Healthy participants
exhibited the opposite pattern in all of these regions. CONCLUSIONS: Hedonic and
interoceptive inferences made by individuals with AN at the sight of food may be
influenced by atypical visceral interoceptive experience, which could contribute
to restrictive eating.
PMID- 28498278
TI - Depression and Survival in a 17-Year Longitudinal Study of People With HIV:
Moderating Effects of Race and Education.
AB - OBJECTIVE: The prevalence of clinically significant depressive symptoms is three
times higher in people living with HIV than in the general population. Although
studies have shown that depression predicts worse course with HIV, few have
investigated its relationship with mortality, and none have had a 17-year follow
up period and been conducted entirely during the time since the advent of
protease inhibitors. METHODS: We followed a diverse sample of HIV-positive people
(N = 177) in the mid-range of illness for a study on stress and coping.
Participants were assessed every 6 months (for 12 years) via blood draw,
questionnaires, and interview. Depression was measured using the Beck Depression
Inventory. The study began in March 1997 and mortality was assessed in April
2014. RESULTS: In the primary analysis depression, analyzed as a continuous
variable, significantly predicted all-cause mortality (hazard ratio = 1.038, 95%
confidence interval = 1.008-1.068). With Beck Depression Inventory scores
dichotomized, the hazard ratio was 2.044 (95% confidence interval = 1.176-3.550).
Furthermore, this result was moderated by race and educational attainment such
that depression only predicted worse survival for non-African Americans and those
with a college education or higher. CONCLUSION: Depression is associated with
worse long-term survival in people with HIV during 17 years of follow-up.
Interventions targeting depression may improve well-being and potentially
survival in individuals with HIV. However, since depression did not predict
survival in African Americans or those with low education, more research is
needed to identify risk factors for long term outcomes in these groups.
PMID- 28498279
TI - Effectiveness of a Stepped, Collaborative, and Coordinated Health Care Network
for Somatoform Disorders (Sofu-Net): A Controlled Cluster Cohort Study.
AB - OBJECTIVE: Stepped, collaborative, and coordinated approaches have been proposed
as the optimal treatment strategy for somatic symptom and related disorders, but
evidence supporting this strategy is lacking. The aim of this study was to assess
the effectiveness of a guideline-based health care network for patients who are
at high risk of somatoform disorder (Sofu-Net). METHODS: In a controlled,
prospective, observer-blinded cluster cohort study, patients who were at high
risk of somatoform disorder were recruited at 18 primary care practices in the
Sofu-Net and at 15 primary care practices that provided care as usual (CAU). The
primary outcome at 6-month follow-up was the rate at which the patients received
mental health treatment since the establishment of Sofu-Net. The secondary
outcomes included the patients' clinical symptom severity. RESULTS: A total of
119 patients in the Sofu-Net intervention group and 100 patients in the CAU
control group who were at high risk of somatoform disorder were followed for 6
months. A significantly greater proportion of Sofu-Net patients than CAU patients
received mental health treatment (47.9% versus 31.0%; odds ratio = 1.96; 95%
confidence interval, 1.07-3.58). However, the Sofu-Net group did not show greater
reductions in clinical symptom burden compared with the CAU group. CONCLUSIONS:
The treatment of somatoform disorders within a guideline-based health care
network resulted in increased rates of mental health treatment but failed to
improve patient clinical outcomes. Future investigations are needed to
investigate the combined value of health care networks with specialized
psychotherapy interventions in patients at high risk of somatic symptom and
related disorders. TRIAL REGISTRATION: ISRCTN55870770.
PMID- 28498280
TI - Immunohistochemical Characterization of the Origins of Metastatic Well
differentiated Neuroendocrine Tumors to the Liver.
AB - Metastatic neoplasms of unknown primary site pose a major challenge to patient
management. As targeted therapies are now being tailored to neuroendocrine tumors
(NETs) of different primary sites, identifying the origin of metastatic NETs has
become increasingly important. Compared with more extensive efforts on metastatic
adenocarcinomas of unknown primary, the literature on metastatic NETs (often to
the liver) is relatively sparse and most studies are based on primary tumors. We
sought to study metastatic well-differentiated NETs to the liver to identify
markers that predict the site of origin. Eighty-five metastatic NETs to the liver
were retrieved from the pathology archive. The primary sites were determined
based on either pathologic review of the primary tumors (in most cases) or
radiologic/clinical findings. Immunohistochemical labeling for TTF1, CDX2, ISL1,
NKX2.2, and PDX1 was performed on either tissue microarrays or whole sections.
The primary sites of the NETs in the study cohort included: pancreas (35%), small
intestine (32%), rectum (8%), stomach (2%), bile duct (1%), lung (9%), and
unknown primary (12%). We found predominant expression of TTF1 in lung carcinoid
(63%), CDX2 in small intestinal (89%) and ISL1 in pancreatic NETs (77%),
respectively. NKX2.2 was mainly expressed in NETs of the digestive organs. PDX1
was detected in a small percentage of pancreatic, small intestinal and the single
bile duct NET. There was no statistically significant association between tumor
grade (World Health Organization G1 vs. G2) and the expression of any of the
above markers. The 3-marker panel (TTF1, CDX2, and ISL1) had sensitivities of
81%, 89%, and 63%, specificities of 100%, 94%, and 100%, positive predictive
values of 100%, 89%, and 100%, and negative predictive values of 84%, 94%, and
96% in separating metastatic NETs into 3 major primary sites: pancreas/rectum,
small intestine, and lung, respectively, with an overall accuracy of 82%.
Furthermore, this panel predicted a primary site for 6 of the 10 NETs of unknown
primary, which reduced the NETs of unknown primary from 12% to 5%. Thus, through
immunohistochemical study of a large series of metastatic NETs to the liver, we
have demonstrated the utility of a 3-marker panel for the identification of one
or more potential primary sites of most metastatic NETs, which could provide
practical guidance in patient management.
PMID- 28498281
TI - MYB Labeling by Immunohistochemistry Is More Sensitive and Specific for Breast
Adenoid Cystic Carcinoma than MYB Labeling by FISH.
AB - Breast adenoid cystic carcinoma (ACC) is a primary breast carcinoma that, like
salivary gland ACC, displays the t(6;9) translocation resulting in the MYB-NFIB
gene fusion and immunopositivity for MYB by immunohistochemistry (IHC). However,
it is not well established whether MYB immunoreactivity or rearrangement can be
used to support a diagnosis of ACC in a malignant basaloid or benign cribriform
breast lesion. Whole sections of primary breast ACC (n=11), collagenous
spherulosis (CS; n=7), and microglandular adenosis (MGA; n=5) and tissue
microarrays containing 16 basal-like, triple-negative breast carcinomas (TNBC)
were labeled for MYB by IHC and underwent MYB fluorescence in situ hybridization
using a break-apart probe. Strong, diffuse nuclear MYB labeling was seen in 100%
ACC compared with no cases of basal-like TNBC, CS, or MGA (P=0.0001). Any degree
of nuclear MYB labeling was seen in 100% ACC compared with 54% of all other cases
(P=0.007), with any labeling seen in 71% CS, 63% basal-like TNBC, and 0% MGA. MYB
rearrangement was detected in 89% (8/9) of evaluable ACC compared with 4% (1/26)
of all other evaluable cases (P=0.0001), with a rearrangement detected in 1 (7%;
n=1/15) evaluable basal-like TNBC. Strong, diffuse nuclear labeling for MYB is
more sensitive than MYB fluorescence in situ hybridization for breast ACC and can
be used to support a diagnosis of ACC in a cribriform or basaloid lesion in the
breast. However, weak and focal labeling should be interpreted with caution as it
can be seen in other benign cribriform and malignant basaloid lesions.
PMID- 28498282
TI - Tumor Spread Through Air Spaces Is an Independent Predictor of Recurrence-free
Survival in Patients With Resected Lung Squamous Cell Carcinoma.
AB - Tumor spread through air spaces (STAS) is a newly recognized pattern of invasion
in lung adenocarcinoma. However, clinical significance of STAS has not yet been
characterized in lung squamous cell carcinoma. In this study, we investigated
whether STAS could determine clinical outcome in Japanese patients with lung
squamous cell carcinoma. We reviewed tumor slides from surgically resected lung
squamous cell carcinomas (n=216). STAS was defined as tumor cells within air
spaces in the lung parenchyma beyond the edge of the main tumor. Tumors were
evaluated for histologic subtypes, tumor budding, and nuclear diameter.
Recurrence-free survival (RFS) was analyzed using the log-rank test and the Cox
proportional hazards model. Tumor STAS was observed in 87 patients (40%),
increasing incidence with lymph node metastasis (P=0.037), higher pathologic
stage (P=0.026), and lymphatic invasion (P=0.033). All cases with STAS showed a
solid nest pattern. The 5-year RFS for patients with STAS was significantly lower
than it was for patients without STAS in all patients (P=0.001) and in stage I
patients (n=134; P=0.041). On multivariate analysis, STAS was an independent
prognostic factor of a worse RFS (hazard ratio=1.61; P=0.023). Patients with STAS
had a significantly increased risk of developing locoregional and distant
recurrences (P=0.012 and 0.001, respectively). We found that tumor STAS was an
independent predictor of RFS in patients with resected lung squamous cell
carcinoma, and it was associated with aggressive tumor behavior.
PMID- 28498283
TI - Synovial Sarcoma of Peripheral Nerves: Analysis of 15 Cases.
AB - Synovial sarcoma of peripheral nerve (SSPN) is rare with only 26 cases reported
in English. SSPN is often mistaken for a benign or malignant peripheral nerve
sheath tumor (PNST) by clinicians and pathologists. Fifteen cases of SSPN were
retrieved from the pathology files of 3 institutions. All tumors arose in a nerve
based on imaging and/or operative findings and the diagnoses were histologically
confirmed. Neuropathic symptoms predominated in 11 women and 4 men, 19- to 62
year-old (median, 39 years) with tumors involving the ulnar (5), median (3),
peroneal (3) or sciatic (2) nerve, or the L4 or T1 nerve root (2). Tumor sizes
ranged from 2 to 13 cm (median, 3.8 cm). The leading clinical diagnosis was PNST
(9). Treatment was surgical (14) supplemented with radiation therapy (8) and
chemotherapy (6). Fourteen tumors were monophasic and 1 was biphasic; 4 had
poorly differentiated (PD) foci (1 rhabdoid). Diagnoses in 12 cases were verified
by fluorescence in situ hybridization, reverse transcription polymerase chain
reaction or both methods. Follow-up in 14 patients (median, 32 mo) revealed that
2/4 patients with PD tumors died with pulmonary metastases; another was alive
with no current evidence of disease (NED) following 2 local recurrences, while
the fourth had NED. In contrast, 9/10 patients without PD tumors were alive (7
NED) and 1 died at 12 months with pulmonary infiltrates. SSPN is under-recognized
clinically and histologically as it mimics benign and malignant PNST. Molecular
analysis is recommended to confirm the diagnosis. PD foci, including rhabdoid
areas, may portend a worse outcome, similar to non-neural-based tumors.
PMID- 28498284
TI - Undifferentiated and Dedifferentiated Endometrial Carcinomas With POLE
Exonuclease Domain Mutations Have a Favorable Prognosis.
AB - POLE exonuclease domain mutations have recently been described in
undifferentiated endometrial carcinoma but, because of the rarity of this
aggressive type of endometrial cancer, their prognostic significance is unknown.
We have analyzed the immunophenotype (ARID1A, MLH1, PMS2, MSH2, MSH6, p53, beta
catenin, and SMARCB1) and mutational status (POLE, PIK3CA, and PTEN) of 21
undifferentiated carcinomas (8 undifferentiated and 13 dedifferentiated
carcinomas). Loss of ARID1A expression was observed in 9 of 19 cases (47%), loss
of expression of at least 1 DNA mismatch repair protein in 7 (7/21; 33%), and p53
immunoreaction was aberrant (mutated/inactivated) in 11 cases (11/21; 52%). All
tumors were negative for beta-catenin. Normal nuclear SMARCB1 (INI1) staining was
found in all but 1 dedifferentiated case. Two undifferentiated and 7
dedifferentiated carcinomas showed POLE exonuclease domain mutations (9/21; 42%).
PIK3CA mutations occurred in six tumors (6/21; 28%) (2 undifferentiated and 4
dedifferentiated carcinomas). PTEN mutations were found in 7 of 15 cases (47%) (4
undifferentiated and 3 dedifferentiated carcinomas). POLE-mutated
undifferentiated and dedifferentiated endometrial carcinomas were more frequently
stage I tumors than similar carcinomas lacking exonuclease domain mutations (7/9;
78% vs. 3/12; 25%; P=0.023) and patients had significantly better outcome
(disease-specific survival) than those without POLE exonuclease domain mutations
(P=0.02). Determination of the POLE mutation status is important for the
management of these patients.
PMID- 28498285
TI - C-MYC and Its Main Ubiquitin Ligase, FBXW7, Influence Cell Proliferation and
Prognosis in Adult T-cell Leukemia/Lymphoma.
AB - Smoldering-type and chronic-type adult T-cell leukemia/lymphomas (ATLL) patients
have relatively indolent clinical courses, but often progress into aggressive
lymphoma-type and acute-type disease. We examined the roles of transcription
factor C-MYC and its ubiquitin ligase FBXW7 in tumor tissues from 137 patients
with ATLL. Immunohistochemical tests showed >=50% of lymphoma cells in 78.7%
(48/61) of lymphoma-type, and 64.9% (24/37) of acute-type samples expressed C
MYC, significantly higher than was seen in smoldering-type (3.6%) and chronic
type (9.1%) samples (P<0.01). Real-time polymerase chain reaction showed C-MYC
mRNA expression in lymphoma-type and acute-type samples were significantly higher
than in smoldering-type (P<0.01). C-MYC expression was highly correlated with its
mRNA levels (rho=0.65, P<0.0001), chromosomal amplification and duplication
(rho=0.3, P=0.045) and MIB1 labeling index (rho=0.69, P<0.0001). Expression of
FBXW7 protein and mRNA in lymphoma-type samples were significantly lower than
those of smoldering-type (P<0.01 for each), and both were inversely correlated
with C-MYC (protein: rho=-0.4, P=0.0002; mRNA: rho=-0.31, P=0.015). Seven
patients with smoldering-type or chronic-type ATLL converted to acute-type, in 4
of whom C-MYC expression increased from <50% to >=50%. Patients with >=50% C-MYC
or MIB1 had significantly worse prognosis than those with <50% C-MYC (P=0.0004)
or MIB1 (P<0.0001), as did those with >=7.5 C-MYC mRNA scores (P=0.033); whereas
significantly better prognosis was associated with >=50% FBXW7 protein (P=0.0006)
or >=0.17 FBXW7 mRNA (P=0.016). C-MYC and FBXW7 affect ATLL proliferation and
progression, and low FBXW7 may increase C-MYC expression. C-MYC was a critical
prognostic factor in ATLL patients.
PMID- 28498286
TI - Biphasic Squamoid Alveolar Renal Cell Carcinoma: 2 Cases in a Family Supporting a
Continuous Spectrum With Papillary Type I Renal Cell Carcinoma.
PMID- 28498287
TI - Molecular Profiling Reveals a Clonal Relationship Between Ovarian Mucinous Tumors
and Corresponding Mural Carcinomatous Nodules.
AB - Benign or malignant mural nodules rarely occur in mucinous tumors (MTs) of the
ovary and malignant nodules can show mesenchymal or epithelial differentiation.
The histogenesis of mural nodules is unclear and it has been suggested that these
may evolve through divergent differentiation of the mucinous neoplasm or
alternatively represent a collision phenomenon. To test these possibilities we
compared the molecular profile of 7 ovarian MTs with their matched mural
carcinomatous nodules (MCNs) by next-generation sequencing. We found identical
KRAS mutations in paired MTs and MCNs in 6 cases, one of which also showed
identical CDH1 mutations in both components. In 1 tumor a KRAS mutation was
detected in the mucinous neoplasm but not in the MCN; however, identical p53
mutations were present in both tumor elements. Unpaired p53 and PTEN mutations
were detected only in the MCN in 2 cases, while mutations in p53 and PIK3CA genes
were observed only in the MT in 2 cases. The overall comparative genomic profile
was consistent with the neoplastic nature of the MCNs and strongly supported
their clonal relationship with the more differentiated mucinous neoplasms. MCNs
possibly develop through the acquisition of additional genomic alterations, such
as p53 and PTEN mutations, resulting in an anaplastic morphologic phenotype. Our
findings also suggest that ovarian MTs with MCNs often arise in KRAS mutant
neoplasms. However, mutations in other genes such as PIK3CA and CDH1 may play a
role in the neoplastic evolution of a subset of these tumors.
PMID- 28498289
TI - Incidence of Cancer in Spinal Deformity Patients Receiving High-Dose (>=40 mg)
Bone Morphogenetic Protein (rhBMP-2).
AB - STUDY DESIGN: Level III, Retrospective observational study. OBJECTIVE: To
determine if there is an increased risk of developing cancer after exposure to
high-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) and if risk is
dose and/or exposure-dependent. SUMMARY OF BACKGROUND DATA: Concerns have been
raised regarding a relationship between rhBMP-2 and cancer. METHODS: A total of
642 adult deformity patients from a single institution receiving a cumulative
rhBMP-2 dose >=40 mg from July, 2002 to July, 2009 were identified. Patients with
a history of surveillance, epidemiology, and end result (SEER) cancer before
rhBMP-2 exposure were excluded. To determine the occurrence of a cancer event,
questionnaires were mailed and telephone follow up attempted for nonresponders.
Only cancers tracked by the National Cancer Institute (NCI) SEER registry were
included. Observed cancer counts were compared to expected cancer counts based on
general population incidence rates within 5-year age strata. Cumulative incidence
competing risk (CICR) modeling was used to evaluate the association between rhBMP
2 exposure and cancer controlling for potential confounding variables. RESULTS:
Forty-nine patients were lost-to-follow up, leaving 593 patients (92.4%; 138
males/455 females) available for analysis. Mean age was 52.8 years at the time of
first exposure. Mean cumulative rhBMP-2 dose was 113.5 mg with 85% having one
exposure (range: 1-8). Mean follow-up [date of exposure to date of death
(regardless of cause) or returned completed questionnaire] was 5.6 +/- 1.9 years;
median follow up was 5.4 years. A total of 342 patients have greater than 5-year
follow up. Minimum follow up was 2.0 years or until occurrence of a SEER cancer.
Our total 8-year cumulative incidence of new SEER cancer accounting for the
competing risk of death was 7.4% for 30 cancers in 593 patients. Fewer cancers
were observed than expected based on general population rates, though the
difference was not statistically significant (expected = 34; standardized
incidence ratio = 0.88, 95% confidence interval, CI = 0.60-1.26). CICR found
neither cumulative rhBMP-2 dose (hazard ratio, HR = 0.995, 95% CI 0.988-1.003; P
= 0.249) nor number of exposures (HR = 0.776, 95% CI 0.359-1.677; P = 0.519)
increased the risk of developing a postexposure cancer after controlling for
known cancer risk factors. CONCLUSION: The incidence of a SEER cancer after rhBMP
2 exposure was similar to incidence reported by the NCI. There were no
significant rhBMP-2 dose or multi-exposure related risks of developing a life
threatening cancer. LEVEL OF EVIDENCE: 3.
PMID- 28498290
TI - The Relationship Between MRI Signal Intensity Changes, Clinical Presentation, and
Surgical Outcome in Degenerative Cervical Myelopathy: Analysis of a Global
Cohort.
AB - STUDY DESIGN: Retrospective analysis of prospective data. OBJECTIVE: To assess
the relationship between MRI signal intensity changes, clinical presentation, and
surgical outcome in degenerative cervical myelopathy (DCM). SUMMARY OF BACKGROUND
DATA: Several studies have sought to assess the extent of spinal cord dysfunction
and the potential for postoperative neurological recovery through the evaluation
of spinal cord signal change on T2-weighted (T2WI) and T1-weighted images (T1WI).
There remains ambiguity if T2WI and T1WI signal changes (1) relate to baseline
severity, and (2) predict neurological recovery after surgical treatment.
METHODS: Four hundred nineteen MRIs from two prospective multicenter studies were
examined. Images were assessed for the presence, levels, and location of spinal
cord signal intensity changes and compared with clinical data. Signal changes
were also evaluated for the prediction of 2-year postoperative outcome using mJOA
parameters. RESULTS: MRIs were categorized by T1WI and T2WI signal change: no
signal change (28.9%), T2WI hyperintensity-only (T2WI-only, 51.8%), and T2WI
hyperintensity and T1WI-hypointensity (T1WI+T2WI, 19.3%). T2WI-hyperintensity was
present at multiple levels in 27% of patients overall. Baseline severity
increased from no signal change to T2WI-only to T2WI+T1WI (P < 0.0001), and there
was an incremental increase in the frequency of signs/symptoms. There were no
differences in outcomes between no signal change and T2WI-only groups. The
presence of T1WI-hypointensity correlated with reduced recovery ratio (P = 0.03)
and likelihood of an optimal surgical outcome (P = 0.005), adjusting for baseline
mJOA. A greater number of T2WI-hyperintensity levels was also associated with
worse baseline severity (P < 0.0001) and recovery ratio (P = 0.001). CONCLUSION:
This analysis of a global cohort of DCM patients shows a stepwise trend toward
increasing impairment from no signal change to T2WI-hypertensity to T1WI
hypointensity. T1WI signal change indicates more permanent injury, portending
decreased functional recovery. T2WI-hyperintensity alone does not predict
outcomes. Multiple levels of T2WI-hyperintensity suggest additional tissue
injury, correlating with worse clinical impairment and recovery potential. LEVEL
OF EVIDENCE: 2.
PMID- 28498291
TI - Multilevel 3D Printing Implant for Reconstructing Cervical Spine With Metastatic
Papillary Thyroid Carcinoma.
AB - : MINI: A 3D printing technology is proposed for reconstructing multilevel
cervical spine (C2-C4) after resection of metastatic papillary thyroid carcinoma.
The personalized porous implant printed in Ti6AL4V provided excellent
physicochemical properties and biological performance, including
biocompatibility, osteogenic activity, and bone ingrowth effect. STUDY DESIGN: A
unique case report. OBJECTIVE: A three-dimensional (3D) printing technology is
proposed for reconstructing multilevel cervical spine (C2-C4) after resection of
metastatic papillary thyroid carcinoma in a middle-age female patient. SUMMARY OF
BACKGROUND DATA: Papillary thyroid carcinoma is a malignant neoplasm with a
relatively favorable prognosis. A metastatic lesion in multilevel cervical spine
(C2-C4) destroys neurological functions and causes local instability. Radical
excision of the metastasis and reconstruction of the cervical vertebrae sequence
conforms with therapeutic principles, whereas the special-shaped multilevel upper
cervical spine requires personalized implants. 3D printing is an additive
manufacturing technology that produces personalized products by accurately
layering material under digital model control via a computer. Reporting of this
recent technology for reconstructing multilevel cervical spine (C2-C4) is rare in
the literature. METHODS: Anterior-posterior surgery was performed in one stage.
Radical resection of the metastatic lesion (C2-C4) and thyroid gland, along with
insertion of a personalized implant manufactured by 3D printing technology, were
performed to rebuild the cervical spine sequences. The porous implant was printed
in Ti6AL4V with perfect physicochemical properties and biological performance,
such as biocompatibility and osteogenic activity. Finally, lateral mass screw
fixation was performed via a posterior approach. RESULTS: Patient neurological
function gradually improved after the surgery. The patient received 11/17 on the
Japanese Orthopedic Association scale and ambulated with a personalized skull
neck-thorax orthosis on postoperative day 11. She received radioiodine I therapy.
The plane x-rays and computed tomography revealed no implant displacement or
subsidence at the 12-month follow-up mark. CONCLUSION: The presented case
substantiates the use of 3D printing technology, which enables the
personalization of products to solve unconventional problems in spinal surgery.
LEVEL OF EVIDENCE: 5.
PMID- 28498292
TI - Effects of Conflicts of Interest on Practice Patterns and Complication Rates in
Spine Surgery.
AB - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: We sought to determine
whether financial relationships with industry had any impact on operative and/or
complication rates of spine surgeons performing fusion surgeries. SUMMARY OF
BACKGROUND DATA: Recent actions from Congress and the Institute of Medicine have
highlighted the importance of conflicts of interest among physicians. Orthopedic
surgeons and neurosurgeons have been identified as receiving the highest amount
of industry payments among all specialties. No study has yet investigated the
potential effects of disclosed industry payments with quality and choices of
patient care. METHODS: A comprehensive database of spine surgeons in the United
States with compiled data of industry payments, operative fusion rates, and
complication rates was created. Practice pattern data were derived from a
publicly available Medicare-based database generated from selected CPT codes from
2011 to 2012. Complication rate data from 2009 to 2013 were extracted from the
ProPublica-Surgeon-Scorecard database, which utilizes postoperative inhospital
mortality and 30-day-readmission for designated conditions as complications of
surgery. Data regarding industry payments from 2013 to 2014 were derived from the
Open Payments website. Surgeons performing <10 fusions, those without
complication data, and those whose identity could not be verified through public
records were excluded. Pearson correlation coefficients and multivariate
regression analyses were used to determine the relationship between industry
payments, operative fusion rate, and/or complication rate. RESULTS: A total of
2110 surgeons met the inclusion criteria for our database. The average operative
fusion rate was 8.8% (SD 4.8%), whereas the average complication rate for lumbar
and cervical fusion was 4.1% and 1.9%, respectively. Pearson correlation analysis
revealed a statistically significant but negligible relationship between
disclosed payments/transactions and both operative fusion and complication rates.
CONCLUSION: Our findings do not support a strong correlation between the payments
a surgeon receives from industry and their decisions to perform spine fusion or
associated complication rates. Large variability in the rate of fusions performed
suggests a poor consensus for indications for spine fusion surgery. LEVEL OF
EVIDENCE: 3.
PMID- 28498293
TI - What Is the Actual 3D Representation of the Rib Vertebra Angle Difference (Mehta
Angle)?
AB - STUDY DESIGN: Cross-sectional study. OBJECTIVE: To establish the relevance of the
conventional two-dimensional (2D) rib vertebra angle difference (RVAD) and the
relationship with the complex three-dimensional (3D) apical morphology in
scoliosis. SUMMARY OF BACKGROUND DATA: The RVAD, also known as Mehta angle,
describes apical rib asymmetry on conventional radiographs and was introduced as
a prognostic factor for curve severity in early onset scoliosis, and later
applied to other types of scoliosis as well. METHODS: An existing idiopathic
scoliosis database of high-resolution computed tomography scans used in previous
work, acquired for spinal navigation, was used. Eighty-eight patients (Cobb angle
46 degrees -109 degrees ) were included. Cobb angle and 2D RVAD, as described by
Mehta, were measured on the conventional radiographs and coronal digitally
reconstructed radiographs (DRR) of the prone computed tomography scans. A
previously validated, semiautomatic image processing technique was used to
acquire complete 3D spinal reconstructions for the measurement of the 3D RVAD in
a reconstructed true coronal plane, axial rotation, and sagittal morphology.
RESULTS: The 2D RVAD on the x-ray was on average 25.3 degrees +/- 11.0 degrees
and 25.6 degrees +/- 12.8 degrees on the DRR (P = 0.990), but in the true 3D
coronal view of the apex, hardly any asymmetry remained (3D RVAD: 3.1 degrees +/
12.5 degrees ; 2D RVAD on x-ray and DRR vs. 3D RVAD: P < 0.001). 2D apical rib
asymmetry in the anatomical coronal plane did not correlate with the same RVAD
measurements in the 3D reconstructed coronal plane of the rotated apex (r =
0.155; P = 0.149). A larger 2D RVAD was found to correlate linearly with
increased axial rotation (r = 0.542; P < 0.001) and apical lordosis (r = 0.522; P
< 0.001). CONCLUSION: The 2D RVAD represents a projection-based composite
radiographic index reflecting the severity of the complex 3D apical morphology
including axial rotation and apical lordosis. It indicates a difference in
severity of the apical deformation. LEVEL OF EVIDENCE: 4.
PMID- 28498294
TI - Target Serum Sodium Levels During Intensive Care Unit Management of Aneurysmal
Subarachnoid Hemorrhage.
AB - INTRODUCTION: Dysnatremia commonly occur in the intensive care unit (ICU)
management of patients with aneurysmal subarachnoid hemorrhage (SAH). However,
detailed management strategies have not been provided even by current guidelines.
The purposes of this study were to examine the association of abnormal serum
sodium levels with unfavorable neurologic outcomes and to identify the target
range of serum sodium in patients with SAH. METHODS: We retrospectively reviewed
all patients who were consecutively hospitalized with a confirmed diagnosis of
SAH between January 2009 and December 2015. Univariate/multivariate analyses were
performed to identify the independent predictors of an unfavorable neurologic
outcome (modified Rankin scale of 3-6 upon hospital discharge). RESULTS: There
were 131 patients included in this study. Unfavorable neurologic outcomes
occurred in 45% of patients. On multiple regression analysis, age, Hunt and
Kosnik grade, and serum sodium levels in the ICU at the maximum [odds ratio (OR),
1.18; 95% CI, 1.05-1.35; P < 0.01] and minimum (OR, 0.88; 95% CI, 0.77-0.99; P =
0.048) values were significantly associated with unfavorable neurologic outcomes.
The receiver operating characteristic curve analysis showed that the cut-off
serum sodium levels were 145 mmol/L for maximum value and 132 mmol/L for minimum
value. Patients with hyponatremia and hypernatremia during the first 2 weeks in
the ICU accounted for 88.2% of patients with an unfavorable neurologic outcome;
whereas, those with normal sodium levels accounted for only 15.6%. CONCLUSIONS:
In patients with SAH, both hyponatremia and hypernatremia during ICU management
were significantly associated with unfavorable neurologic outcomes.
PMID- 28498295
TI - Epidemiology of Anaphylactic Shock and its Related Mortality in Hospital Patients
in Taiwan: A Nationwide Population-Based Study.
AB - Anaphylactic shock is potentially life-threatening. However, there is a paucity
of data about its incidence and associated mortality, particularly in Asian
populations. We aimed to investigate the epidemiology of anaphylactic shock and
its related mortality after the hospitalization of patients in the general
population of Taiwan. The National Health Insurance Research Database was used to
identify patients with anaphylactic shock and estimate its incidence for
inpatients sampled from 2005 to 2012. The pattern of anaphylactic shock and
anaphylactic shock-related mortality rate was also examined. Of 22,080,199
patients who were admitted to hospitals from 2005 to 2012, there were 2,289
incident cases of anaphylactic shock and 2,219 people were included. Incidence of
hospitalizations due to anaphylactic shock ranged from 12.71 to 13.23 per million
of the population between 2005 and 2012. The incidence of anaphylactic shock in
our study was substantially lower than other western countries, including the
United States. There were 24 deaths due to drug-induced anaphylactic shock among
the hospitalizations; overall mortality rate was 1.08%. Eighteen (0.81%) patients
died within 30 days; 22 (0.99%) died within 2 months following the anaphylactic
shock. The highest incidence occurred in patients aged 70-79 years. Conversely,
food-induced anaphylactic shock was not influenced by age. In conclusion, drug
induced anaphylactic shock was a major cause of death due to anaphylactic shock
in hospitalized patients. Most cases of anaphylactic shock occurred in the older
population, and the mortality rate was lower in females than in males, though the
difference was not significant.
PMID- 28498296
TI - Interleukin-22 Prevents Microbial Dysbiosis and Promotes Intestinal Barrier
Regeneration Following Acute Injury.
AB - Intestine barrier disruption and bacterial translocation can contribute to sepsis
and multiple organ failure, leading causes of mortality in burn-injured patients.
In addition, findings suggest that ethanol (alcohol) intoxication at the time of
injury worsens symptoms associated with burn injury. We have previously shown
that interleukin-22 (IL-22) protects from intestinal leakiness and prevents
overgrowth of gram-negative bacteria following ethanol and burn injury, but how
IL-22 mediates these effects has not been established. Here, utilizing a mouse
model of ethanol and burn injury, we show that the combined insult results in a
significant loss of proliferating cells within small intestine crypts and
increases Enterobacteriaceae copies, despite elevated levels of the antimicrobial
peptide lipocalin-2. IL-22 administration restored numbers of proliferating cells
within crypts, significantly increased Reg3beta, Reg3gamma, lipocalin-2 AMP
transcript levels in intestine epithelial cells, and resulted in complete
reduction of Enterobacteriaceae in the small intestine. Knockout of signal
transducer and activator of transcription factor-3 (STAT3) in intestine
epithelial cells resulted in complete loss of IL-22 protection, demonstrating
that STAT3 is required for intestine barrier protection following ethanol
combined with injury. Together, these findings suggest that IL-22/STAT3 signaling
is critical to gut barrier integrity and targeting this pathway may be of
beneficial clinical relevance following burn injury.
PMID- 28498297
TI - Gastrointestinal Colonization of Candida Albicans Increases Serum (1->3)-beta-D
Glucan, without Candidemia, and Worsens Cecal Ligation and Puncture Sepsis in
Murine Model.
AB - The role of intestinal Candida albicans in bacterial sepsis, in the absence of
candidemia, was investigated in murine models. Live C albicans or normal saline
solution (NSS) was administered orally once, followed by 5 days of daily oral
antibiotic-mixtures (ATB). Cecal ligation and puncture (CLP) was then performed
to induce sepsis.Fecal Candida was detected by culture only in models with
Candida administration. Oral Candida administration with/without ATB enhanced gut
pathogenic bacteria as determined by microbiome analysis. Despite negative
candidemia, serum (1->3)-beta-D-glucan (BG) was higher in CLP with Candida
preconditioning models than in CLP-controls (NSS-preconditioning) at 6 and/or 18
h post-CLP. Blood bacterial burdens were not increased with Candida
administration.Additionally, CLP with high-dose Candida (10 colony forming units)
induced higher levels of fecal Candida, serum BG, serum IL-6, and mortality than
the lowest dose (100 colony forming units). Interestingly, fluconazole attenuated
fecal Candida and improved survival in mice with live-Candida administration, but
not in the CLP-controls. Heat-killed Candida preparations or their supernatants
reduced bone marrow-derived macrophage killing activity in vitro but enhanced
cytokine production.In conclusion, intestinal abundance of fungi and/or fungal
molecules was associated with increased bacterial sepsis severity, perhaps
through cytokine storm induction and/or decreased macrophage killing activity.
These observations suggest that further investigation of the potential role of
intestinal fungal burdens in sepsis is warranted.
PMID- 28498298
TI - Hydrogen Sulfide: A Potential Novel Therapy for the Treatment of Ischemia.
AB - Hydrogen sulfide (H2S) is a novel signaling molecule most recently found to be of
fundamental importance in cellular function as a regulator of apoptosis,
inflammation, and perfusion. Mechanisms of endogenous H2S signaling are poorly
understood; however, signal transmission is thought to occur via persulfidation
at reactive cysteine residues on proteins. Although much has been discovered
about how H2S is synthesized in the body, less is known about how it is
metabolized. Recent studies have discovered a multitude of different targets for
H2S therapy, including those related to protein modification, intracellular
signaling, and ion channel depolarization. The most difficult part of studying
hydrogen sulfide has been finding a way to accurately and reproducibly measure
it. The purpose of this review is to: elaborate on the biosynthesis and
catabolism of H2S in the human body, review current knowledge of the mechanisms
of action of this gas in relation to ischemic injury, define strategies for
physiological measurement of H2S in biological systems, and review potential
novel therapies that use H2S for treatment.
PMID- 28498299
TI - Machine Learning for Predicting Outcomes in Trauma.
AB - To date, there are no reviews on machine learning (ML) for predicting outcomes in
trauma. Consequently, it remains unclear as to how ML-based prediction models
compare in the triage and assessment of trauma patients. The objective of this
review was to survey and identify studies involving ML for predicting outcomes in
trauma, with the hypothesis that models predicting similar outcomes may share
common features but the performance of ML in these studies will differ greatly.
MEDLINE and other databases were searched for studies involving trauma and ML.
Sixty-five observational studies involving ML for the prediction of trauma
outcomes met inclusion criteria. In total 2,433,180 patients were included in the
studies. The studies focused on prediction of the following outcome measures:
survival/mortality (n = 34), morbidity/shock/hemorrhage (n = 12), hospital length
of stay (n = 7), hospital admission/triage (n = 6), traumatic brain injury (n =
4), life-saving interventions (n = 5), post-traumatic stress disorder (n = 4),
and transfusion (n = 1). Six studies were prospective observational studies. Of
the 65 studies, 33 used artificial neural networks for prediction. Importantly,
most studies demonstrated the benefits of ML models. However, algorithm
performance was assessed differently by different authors. Sensitivity
specificity gap values varied greatly from 0.035 to 0.927. Notably, studies
shared many features for model development. A common ML feature base may be
determined for predicting outcomes in trauma. However, the impact of ML will
require further validation in prospective observational studies and randomized
clinical trials, establishment of common performance criteria, and high-quality
evidence about clinical and economic impacts before ML can be widely accepted in
practice.
PMID- 28498300
TI - Volatile Decay Products in Breath During Peritonitis Shock are Attenuated by
Enteral Blockade of Pancreatic Digestive Proteases.
AB - There is a need to develop markers for early detection of organ failure in shock
that can be noninvasively measured at point of care. We explore here the use of
volatile organic compounds (VOCs) in expired air in a rat peritonitis shock
model. Expired breath samples were collected into Tedlar gas bags and analyzed by
standardized gas chromatography. The gas chromatograms were digitally analyzed
for presence of peak amounts over a range of Kovach indices. Following the
induction of peritonitis, selected volatile compounds were detected within about
1 h, which remained at elevated amounts over a 6 h observation period. These VOCs
were not present in control animals without peritonitis. Comparisons with know
VOCs indicate that they include 1,4-diaminobutane and trimethylamine N-oxide.
When pancreatic digestive proteases were blocked with tranexamic acid in the
intestine and peritoneum, a procedure that serves to reduce organ failure in
shock, the amounts of VOCs in the breath decreased spontaneously to control
values without peritonitis. These results indicate that peritonitis shock is
accompanied by development of volatile organic compounds that may be generated by
digestive enzymes in the small intestine. VOCs may serve as indicators for
detection of early forms of autodigestion by digestive proteases.
PMID- 28498301
TI - Seroprevalence of Hepatitis A Twelve Years After the Implementation of Toddlers'
Vaccination: A Population-Based Study in Israel.
AB - BACKGROUND: In 1999, Israel became the first country to introduce an inactivated
hepatitis A vaccine into its national childhood vaccination program. The
objective of the present study was to evaluate the seroprevalence of hepatitis A
virus antibodies in the Israeli population before and after the introduction of
the program. METHODS: A cross-sectional serosurvey using the National Serum Bank
was conducted on 1883 and 2027 serum samples collected before and after
introduction of the vaccine, respectively. Serologic tests for the presence of
hepatitis A IgG antibodies were performed using an automated enzyme-linked
fluorescent assay. RESULTS: The age-adjusted seroprevalence rates of hepatitis A
virus antibodies before implementation of hepatitis A vaccination program were
47.1% [95% confidence interval (CI): 44.7%-49.5%] among Jews and 82.8% (95% CI:
79.6%-85.9%) among Arabs, increasing 12 years after to 67.4% (95% CI: 64.7%
70.0%) and 88.2% (95% CI: 86.1%-90.2%), respectively. CONCLUSIONS: The
seropositivity rate among Jews and Arabs increased significantly among the
cohorts included in the program. However, among Jews, a significant increase in
seropositivity was also detected among age groups not included in the vaccination
program. The decrease in the incidence of hepatitis A in Israel is a consequence
of high vaccine uptake, persistent seropositivity rates after vaccination and the
considerable number of people vaccinated beyond the program.
PMID- 28498302
TI - Reaction of the BCG Scar in the Acute Phase of Kawasaki Disease in Mexican
Children.
AB - BACKGROUND: Kawasaki disease (KD) is an acute self-limited systemic vasculitis
that primarily affects children <5 years old. There is no specific diagnostic
test. A reaction at the Bacille Calmette-Guerin (BCG) inoculation site has been
reported as a common finding in patients with KD where BCG vaccination is
mandatory. The purpose of this study was to evaluate the frequency of
reactivation of the BCG in Mexican children diagnosed with KD. METHODS: A
retrospective study of all patients diagnosed with KD from August 1, 1995, to
August 31, 2015, at our Institution was performed. The clinical profile,
laboratory results, treatment used and coronary artery abnormalities in the BCG
reactive and the BCG nonreactive groups were analyzed and compared. RESULTS: We
included 399 patients with KD. Ninety-seven (24.3%) had BCG reaction at the
inoculation site. The BCG(+) group was younger than the BCG(-) group (P < 0.000).
There were 18 (18.55%) incomplete cases in the BCG(+) group compared with 65
(21.52%) in the BCG(-) group without statistical significance. The BCG+ group
developed coronary artery aneurysms in 37 cases and the BCG(-) group developed
coronary artery aneurysms in 111 cases without statistical significance.
Multivariate analysis showed that younger age at diagnosis was the only variable
associated with a reaction at the BCG inoculation site in patients with KD.
CONCLUSIONS: In Mexico, a country with a National BCG Vaccination Program and a
low incidence of KD, reaction at the BCG inoculation site could be a useful
diagnostic sign of KD.
PMID- 28498303
TI - Varicella Zoster Virus-Associated Necrotizing Retinitis After Chickenpox in a 10
Year-Old Female: A Case Report.
AB - A necrotizing retinitis in children is a rare but vision-threatening ocular
complication of chickenpox. We report a 10-year-old girl who developed chickenpox
1 month before presenting with panuveitis and necrotizing retinitis. After prompt
antiviral treatment, her inflammatory signs were resolved. Early detection and
treatment of varicella zoster-associated necrotizing retinitis after chickenpox
can achieve good visual outcome.
PMID- 28498304
TI - Pharmaceutical Dosing Errors at a Pediatric HIV Clinic in Mwanza, Tanzania.
AB - The outpatient medication dosing error rate at a pediatric HIV clinic in Mwanza,
Tanzania, was about 1 in every 34 prescriptions. Young children were at highest
risk of a dosing error likely because of dose changes with growth and also the
inconsistent supply of pediatric formulations. Majority of errors occurred at
consecutive visits suggesting clinicians reordered medication without double
checking dosing.
PMID- 28498305
TI - Aminoglycosides Monotherapy as First-Line Treatment for Febrile Urinary Tract
Infection in Children.
AB - We report a retrospective monocentric descriptive study performed in CHI Creteil
for 20 months to describe the management and outcome of amikacin monotherapy as
an alternative to third-generation cephalosporins for empiric treatment of
febrile urinary tract infection (FUTI) in children. Data were analyzed for 151
children, and 90 selected cases were classified as certain or highly probable
FUTI. Escherichia coli infection was found in 89 cases. In all patients, fever
was resolved within 72 hours after beginning amikacin treatment. Only 5.3% of
children were febrile after 48 hours. The mean amikacin treatment duration was
3.05 +/- 0.13 days before oral treatment began (guided by antibiotic
susceptibility testing). Amikacin monotherapy seems effective for the initial
management of FUTI in children.
PMID- 28498307
TI - An Improved Design of the Spiral-Coil EMAT for Enhancing the Signal Amplitude.
AB - The low energy transition efficiency of electromagnetic ultrasonic transducer
(EMAT) is a common problem in practical application. For the purpose of enhancing
the amplitude of the received signal, an improved double-coil bulk wave EMAT is
proposed for the thickness measurement of metallic block. This new configuration
of magnets consists of a solid cylindrical magnet and a ring-shaped magnet
encircling the outer side of the solid cylindrical one. A double-coil was applied
instead of a single spiral-coil. Numerical simulations were performed to analyze
and optimize the proposed configuration of the EMAT by the 2-D axisymmetric
finite element model (FEM). The experiment effectively verifies the rationality
of the new configuration and the feasibility of improving the signal strength.
PMID- 28498306
TI - A Conserved Residue, Tyrosine (Y) 84, in H5N1 Influenza A Virus NS1 Regulates IFN
Signaling Responses to Enhance Viral Infection.
AB - The non-structural protein, NS1, is a virulence factor encoded by influenza A
viruses (IAVs). In this report, we provide evidence that the conserved residue,
tyrosine (Y) 84, in a conserved putative SH2-binding domain in
A/Duck/Hubei/2004/L-1 [H5N1] NS1 is critical for limiting an interferon (IFN)
response to infection. A phenylalanine (F) substitution of this Y84 residue
abolishes NS1-mediated downregulation of IFN-inducible STAT phosphorylation, and
surface IFNAR1 expression. Recombinant IAV (rIAV) [H1N1] expressing A/Grey
Heron/Hong Kong/837/2004 [H5N1] NS1-Y84F (rWSN-GH-NS1-Y84F) replicates to lower
titers in human lung epithelial cells and is more susceptible to the antiviral
effects of IFN-beta treatment compared with rIAV expressing the intact H5N1 NS1
(rWSN-GH-NS1-wt). Cells infected with rWSN-GH-NS1-Y84F express higher levels of
IFN stimulated genes (ISGs) associated with an antiviral response compared with
cells infected with rWSN-GH-NS1-wt. In mice, intranasal infection with rWSN-GH
NS1-Y84F resulted in a delay in onset of weight loss, reduced lung pathology,
lower lung viral titers and higher ISG expression, compared with mice infected
with rWSN-GH-NS1-wt. IFN-beta treatment of mice infected with rWSN-GH-NS1-Y84F
reduced lung viral titers and increased lung ISG expression, but did not alter
viral titers and ISG expression in mice infected with rWSN-GH-NS1-wt. Viewed
altogether, these data suggest that the virulence associated with this conserved
Y84 residue in NS1 is, in part, due to its role in regulating the host IFN
response.
PMID- 28498308
TI - Metal-Organic Frameworks as Active Materials in Electronic Sensor Devices.
AB - In the past decade, advances in electrically conductive metal-organic frameworks
(MOFs) and MOF-based electronic devices have created new opportunities for the
development of next-generation sensors. Here we review this rapidly-growing
field, with a focus on the different types of device configurations that have
allowed for the use of MOFs as active components of electronic sensor devices.
PMID- 28498309
TI - Effective Social Relationship Measurement and Cluster Based Routing in Mobile
Opportunistic Networks.
AB - In mobile opportunistic networks, the social relationship among nodes has an
important impact on data transmission efficiency. Motivated by the strong share
ability of "circles of friends" in communication networks such as Facebook,
Twitter, Wechat and so on, we take a real-life example to show that social
relationships among nodes consist of explicit and implicit parts. The explicit
part comes from direct contact among nodes, and the implicit part can be measured
through the "circles of friends". We present the definitions of explicit and
implicit social relationships between two nodes, adaptive weights of explicit and
implicit parts are given according to the contact feature of nodes, and the
distributed mechanism is designed to construct the "circles of friends" of nodes,
which is used for the calculation of the implicit part of social relationship
between nodes. Based on effective measurement of social relationships, we propose
a social-based clustering and routing scheme, in which each node selects the
nodes with close social relationships to form a local cluster, and the self
control method is used to keep all cluster members always having close
relationships with each other. A cluster-based message forwarding mechanism is
designed for opportunistic routing, in which each node only forwards the copy of
the message to nodes with the destination node as a member of the local cluster.
Simulation results show that the proposed social-based clustering and routing
outperforms the other classic routing algorithms.
PMID- 28498310
TI - Selective Expression of Flt3 within the Mouse Hematopoietic Stem Cell
Compartment.
AB - The fms-like tyrosine kinase 3 (Flt3) is a cell surface receptor that is
expressed by various hematopoietic progenitor cells (HPC) and Flt3-activating
mutations are commonly present in acute myeloid and lymphoid leukemias. These
findings underscore the importance of Flt3 to steady-state and malignant
hematopoiesis. In this study, the expression of Flt3 protein and Flt3 mRNA by
single cells within the hematopoietic stem cell (HSC) and HPC bone marrow
compartments of C57/BL6 mice was investigated using flow cytometry and the
quantitative reverse transcription polymerase chain reaction. Flt3 was
heterogeneously expressed by almost all of the populations studied, including
long-term reconstituting HSC and short-term reconstituting HSC. The
erythropoietin receptor (EpoR) and macrophage colony-stimulating factor receptor
(M-CSFR) were also found to be heterogeneously expressed within the multipotent
cell compartments. Co-expression of the mRNAs encoding Flt3 and EpoR rarely
occurred within these compartments. Expression of both Flt3 and M-CSFR protein at
the surface of single cells was more commonly observed. These results emphasize
the heterogeneous nature of HSC and HPC and the new sub-populations identified
are important to understanding the origin and heterogeneity of the acute myeloid
leukemias.
PMID- 28498312
TI - A Formal Approach to the Selection by Minimum Error and Pattern Method for Sensor
Data Loss Reduction in Unstable Wireless Sensor Network Communications.
AB - There are wireless networks in which typically communications are unsafe. Most
terrestrial wireless sensor networks belong to this category of networks. Another
example of an unsafe communication network is an underwater acoustic sensor
network (UWASN). In UWASNs in particular, communication failures occur frequently
and the failure durations can range from seconds up to a few hours, days, or even
weeks. These communication failures can cause data losses significant enough to
seriously damage human life or property, depending on their application areas. In
this paper, we propose a framework to reduce sensor data loss during
communication failures and we present a formal approach to the Selection by
Minimum Error and Pattern (SMEP) method that plays the most important role for
the reduction in sensor data loss under the proposed framework. The SMEP method
is compared with other methods to validate its effectiveness through experiments
using real-field sensor data sets. Moreover, based on our experimental results
and performance comparisons, the SMEP method has been validated to be better than
others in terms of the average sensor data value error rate caused by sensor data
loss.
PMID- 28498311
TI - Differential Immune Responses to New World and Old World Mammalian Arenaviruses.
AB - Some New World (NW) and Old World (OW) mammalian arenaviruses are emerging,
zoonotic viruses that can cause lethal hemorrhagic fever (HF) infections in
humans. While these are closely related RNA viruses, the infected hosts appear to
mount different types of immune responses against them. Lassa virus (LASV)
infection, for example, results in suppressed immune function in progressive
disease stage, whereas patients infected with Junin virus (JUNV) develop overt
pro-inflammatory cytokine production. These viruses have also evolved different
molecular strategies to evade host immune recognition and activation. This paper
summarizes current progress in understanding the differential immune responses to
pathogenic arenaviruses and how the information can be exploited toward the
development of vaccines against them.
PMID- 28498313
TI - Identifying the Genes Regulated by AtWRKY6 Using Comparative Transcript and
Proteomic Analysis under Phosphorus Deficiency.
AB - Phosphorus (P) is an important mineral nutrient for plant growth and development.
Overexpressing AtWRKY6 (35S:WRKY6-9) was more sensitive and wrky6 (wrky6-1) was
more resistant under low Pi conditions. To better understand the function of
AtWRKY6 under low phosphate stress conditions, we applied two-dimensional gel
electrophoresis (2-DE) to analyse differentially expressed proteins in the shoots
and roots between wild type, 35S:WRKY6-9 and wrky6-1 after phosphorus deficiency
treatment for three days. The results showed 88 differentially abundant protein
spots, which were identified between the shoots and roots of 35S:WRKY6-9 and
wrky6-1 plants. In addition, 59 differentially expressed proteins were identified
in the leaves and roots of 35S:WRKY6-9 plants. After analysis, 9 genes with W-box
elements in their promoter sequences were identified in the leaves, while 6 genes
with W-box elements in their promoter sequences were identified in the roots. A
total of 8 genes were identified as potential target genes according to the
quantitative PCR (QPCR) and two dimension difference gel electrophoresis, (2D
DIGE) results, including ATP synthase, gln synthetase, nitrilase, 14-3-3 protein,
carbonic anhydrases 2, and tryptophan synthase. These results provide important
information concerning the AtWRKY6 regulation network and reveal potential vital
target genes of AtWRKY6 under low phosphorus stress. two dimension difference gel
electrophoresis, 2D-DIGE.
PMID- 28498314
TI - Photoactive Hybrid Catalysts Based on Natural and Synthetic Polymers: A
Comparative Overview.
AB - In the present review, we would like to draw the reader's attention to the
polymer-based hybrid materials used in photocatalytic processes for efficient
degradation of organic pollutants in water. These inorganic-organic materials
exhibit unique physicochemical properties due to the synergistic effect
originating from the combination of individual elements, i.e., photosensitive
metal oxides and polymeric supports. The possibility of merging the structural
elements of hybrid materials allows for improving photocatalytic performance
through (1) an increase in the light-harvesting ability; (2) a reduction in
charge carrier recombination; and (3) prolongation of the photoelectron lifetime.
Additionally, the great majority of polymer materials exhibit a high level of
resistance against ultraviolet irradiation and improved corrosion resistance.
Taking into account that the chemical and environmental stability of the hybrid
catalyst depends, to a great extent, on the functional support, we highlight
benefits and drawbacks of natural and synthetic polymer-based photocatalytic
materials and pay special attention to the fact that the accessibility of
synthetic polymeric materials derived from petroleum may be impeded due to
decreasing amounts of crude oil. Thus, it is necessary to look for cheap and
easily available raw materials like natural polymers that come from, for
instance, lignocellulosic wastes or crustacean residues to meet the demand of the
"plastic" market.
PMID- 28498315
TI - Factors Associated with Stunting among Children Aged 0 to 59 Months from the
Central Region of Mozambique.
AB - The objective of this study was to identify the major socio-demographic, health,
and environmental determinants of stunting among children aged 0-59 months from
the Tete province (Mozambique) and offering useful information for future
healthcare strategies and interventions. A case-control study was conducted among
282 (162 boys; 120 girls) children under five years of age from the central
region of Mozambique between 1 May and 3 June 2014. Children with stunting (HAZ <
-2 SD according to the WHO Child Growth Standards in 2006) were considered as
cases and those who had a Z-score < -2 SD were considered as controls. We
collected data related to mothers and children and their environment, and they
were assessed in two groups to find a possible association. The software used for
data analysis was the SPSS(r)(version, 21.0) using descriptive statistics, t
test, ANOVA, chi-square analyses, bivariate comparisons, and stepwise multiple
logistic regression analysis. The results showed that birth weight, mother's
educational status, maternal occupation, living in a rural area, family size,
number of children under five years of age in the household, cooking with
charcoal, inhabiting wooden or straw housing or housing without proper floors,
overall duration of breastfeeding as well as duration of exclusive breastfeeding,
and time of initiation of complementary feeding were significantly related to
stunting. Thus, appropriate nutritional intervention programmes considering these
determinants and the dissemination of knowledge at the population level related
to undernutrition are necessary to ameliorate the children's nutritional status.
PMID- 28498316
TI - Design, Synthesis and Anti-Proliferative Activities of 2,6-Substituted Thieno[3,2
d]pyrimidine Derivatives Containing Electrophilic Warheads.
AB - Thieno[3,2-d]pyrimidine as an effective pharmacophore has been extensively
studied. However, its 2,6-substituted derivatives are rarely reported. In the
present study, eighteen 2,6-substituted thieno[3,2-d]pyrimidine derivatives
containing electrophilic warheads were designed based on the first known
Fibroblast growth factor receptor-4 (FGFR4) inhibitor Blu9931. Unexpectedly, all
of the derivatives exhibited negligible activity against FGFR4. However, most of
the target compounds exhibited antiproliferative activities against four human
cancer cell lines, including A431, NCI-H1975, Ramos and SNU-16. Compound 12
showed the most potent antiproliferative activities on the above four cell lines
with IC50 values of 1.4 MUM, 1.2 MUM, 0.6 MUM, and 2.6 MUM, respectively.
Additionally, the antiproliferative activity of 12 against MDA-MB-221 proved that
12 had the selectivity towards certain tumor cell lines. Furthermore, preliminary
structure-activity relationship analysis was discussed based on the experimental
data.
PMID- 28498317
TI - Development of Data Registration and Fusion Methods for Measurement of Ultra
Precision Freeform Surfaces.
AB - The measurement of ultra-precision freeform surfaces commonly requires several
datasets from different sensors to realize holistic measurements with high
efficiency. The effectiveness of the technology heavily depends on the quality of
the data registration and fusion in the measurement process. This paper presents
methods and algorithms to address these issues. An intrinsic feature pattern is
proposed to represent the geometry of the measured datasets so that the
registration of the datasets in 3D space is casted as a feature pattern
registration problem in a 2D plane. The accuracy of the overlapping area is
further improved by developing a Gaussian process based data fusion method with
full consideration of the associated uncertainties in the measured datasets.
Experimental studies are undertaken to examine the effectiveness of the proposed
method. The study should contribute to the high precision and efficient
measurement of ultra-precision freeform surfaces on multi-sensor systems.
PMID- 28498318
TI - DNA Methylation Dynamics and Cocaine in the Brain: Progress and Prospects.
AB - Cytosine modifications, including DNA methylation, are stable epigenetic marks
that may translate environmental change into transcriptional regulation. Research
has begun to investigate DNA methylation dynamics in relation to cocaine use
disorders. Specifically, DNA methylation machinery, including methyltransferases
and binding proteins, are dysregulated in brain reward pathways after chronic
cocaine exposure. In addition, numerous methylome-wide and candidate promoter
studies have identified differential methylation, at the nucleotide level, in
rodent models of cocaine abuse and drug seeking behavior. This review highlights
the current progress in the field of cocaine-related methylation, and offers
considerations for future research.
PMID- 28498319
TI - CTC-mRNA (AR-V7) Analysis from Blood Samples-Impact of Blood Collection Tube and
Storage Time.
AB - Circulating tumour cells (CTCs) are an emerging resource for monitoring cancer
biomarkers. New technologies for CTC isolation and biomarker detection are
increasingly sensitive, however, the ideal blood storage conditions to preserve
CTC-specific mRNA biomarkers remains undetermined. Here we tested the
preservation of tumour cells and CTC-mRNA over time in common anticoagulant
ethylene-diamine-tetra-acetic acid (EDTA) and acid citrate dextrose solution B
(Citrate) blood tubes compared to preservative-containing blood tubes. Blood
samples spiked with prostate cancer cells were processed after 0, 24, 30, and 48
h storage at room temperature. The tumour cell isolation efficiency and the mRNA
levels of the prostate cancer biomarkers androgen receptor variant 7 (AR-V7) and
total AR, as well as epithelial cell adhesion molecule (EpCAM) were measured.
Spiked cells were recovered across all storage tube types and times.
Surprisingly, tumour mRNA biomarkers were readily detectable after 48 h storage
in EDTA and Citrate tubes, but not in preservative-containing tubes. Notably, AR
V7 expression was detected in prostate cancer patient blood samples after 48 h
storage in EDTA tubes at room temperature. This important finding presents
opportunities for measuring AR-V7 expression from clinical trial patient samples
processed within 48 h-a much more feasible timeframe compared to previous
recommendations.
PMID- 28498321
TI - BDNF Binds Its Pro-Peptide with High Affinity and the Common Val66Met
Polymorphism Attenuates the Interaction.
AB - Most growth factors are initially synthesized as precursors then cleaved into
bioactive mature domains and pro-domains, but the biological roles of pro-domains
are poorly understood. In the present study, we investigated the pro-domain (or
pro-peptide) of brain-derived neurotrophic factor (BDNF), which promotes neuronal
survival, differentiation and synaptic plasticity. The BDNF pro-peptide is a post
processing product of the precursor BDNF. Using surface plasmon resonance and
biochemical experiments, we first demonstrated that the BDNF pro-peptide binds to
mature BDNF with high affinity, but not other neurotrophins. This interaction was
more enhanced at acidic pH than at neutral pH, suggesting that the binding is
significant in intracellular compartments such as trafficking vesicles rather
than the extracellular space. The common Val66Met BDNF polymorphism results in a
valine instead of a methionine in the pro-domain, which affects human brain
functions and the activity-dependent secretion of BDNF. We investigated the
influence of this variation on the interaction between BDNF and the pro-peptide.
Interestingly, the Val66Met polymorphism stabilized the heterodimeric complex of
BDNF and its pro-peptide. Furthermore, compared with the Val-containing pro
peptide, the complex with the Met-type pro-peptide was more stable at both acidic
and neutral pH, suggesting that the Val66Met BDNF polymorphism forms a more
stable complex. A computational modeling provided an interpretation to the role
of the Val66Met mutation in the interaction of BDNF and its pro-peptide. Lastly,
we performed electrophysiological experiments, which indicated that the BDNF pro
peptide, when pre-incubated with BDNF, attenuated the ability of BDNF to inhibit
hippocampal long-term depression (LTD), suggesting a possibility that the BDNF
pro-peptide may interact directly with BDNF and thereby inhibit its availability.
It was previously reported that the BDNF pro-domain exerts a chaperone-like
function and assists the folding of the BDNF protein. However, our results
suggest a new role for the BDNF pro-domain (or pro-peptide) following proteolytic
cleave of precursor BDNF, and provide insight into the Val66Met polymorphism.
PMID- 28498322
TI - Valproic Acid Induces Endocytosis-Mediated Doxorubicin Internalization and Shows
Synergistic Cytotoxic Effects in Hepatocellular Carcinoma Cells.
AB - Valproic acid (VPA), a well-known histone deacetylase (HDAC) inhibitor, is used
as an anti-cancer drug for various cancers, but the synergistic anti-cancer
effect of VPA and doxorubicin (DOX) combination treatment and its potential
underlying mechanism in hepatocellular carcinoma (HCC) remain to be elucidated.
Here, we evaluate the mono- and combination-therapy effects of VPA and DOX in HCC
and identify a specific and efficient, synergistic anti-proliferative effect of
the VPA and DOX combination in HCC cells, especially HepG2 cells; this effect was
not apparent in MIHA cells, a normal hepatocyte cell line. The calculation of the
coefficient of drug interaction confirmed the significant synergistic effect of
the combination treatment. Concurrently, the synergistic apoptotic cell death
caused by the VPA and DOX combination treatment was confirmed by Hoechst nuclear
staining and Western blot analysis of caspase-3 and poly (ADP-ribose) polymerase
(PARP) activation. Co-treatment with VPA and DOX enhanced reactive oxygen species
(ROS) generation and autophagy, which were clearly attenuated by ROS and
autophagy inhibitors, respectively. Furthermore, as an indication of the
mechanism underlying the synergistic effect, we observed that DOX
internalization, which was induced in the VPA and DOX combination-treated group,
occurred via by the caveolae-mediated endocytosis pathway. Taken together, our
study uncovered the potential effect of the VPA and DOX combination treatment
with regard to cell death, including induction of cellular ROS, autophagy, and
the caveolae-mediated endocytosis pathway. Therefore, these results present novel
implications in drug delivery research for the treatment of HCC.
PMID- 28498324
TI - Geographical Variation in Breast Cancer Outcomes.
AB - n/a.
PMID- 28498323
TI - Alkamides from Anacyclus pyrethrum L. and Their in Vitro Antiprotozoal Activity.
AB - In our ongoing study to evaluate the antiprotozoal activity of alkamides from
Asteraceae, a dichloromethane extract from the roots of Anacycluspyrethrum L.
showed a moderate in vitro activity against the NF54 strain of Plasmodium
falciparum and against Leishmaniadonovani (amastigotes, MHOM/ET/67/L82 strain).
Seven pure alkamides and a mixture of two further alkamides were isolated by
column chromatography followed by preparative high performance liquid
chromatography. The alkamides were identified by mass- and NMR-spectroscopic
methods as tetradeca-2E,4E-dien-8,10-diynoic acid isobutylamide (anacycline, 1),
deca-2E,4E-dienoic acid isobutylamide (pellitorine, 2), deca-2E,4E,9-trienoic
acid isobutylamide (3), deca-2E,4E-dienoic acid 2-phenylethylamide (4), undeca
2E,4E-dien-8,10-diynoic acid isopentylamide (5), tetradeca-2E,4E,12Z-trien-8,10
diynoic acid isobutylamide (6), and dodeca-2E,4E-dien acid 4-hydroxy-2
phenylethylamide (7). Two compounds-undeca-2E,4E-dien-8,10-diynoic acid 2
phenylethylamide (8) and deca-2E,4E-dienoic acid 4-hydroxy-2-phenylethylamide (9)
were isolated as an inseparable mixture (1:4). Compounds 3, 4, and 5 were
isolated from Anacycluspyrethrum L. for the first time. While compounds 4 and 5
were previously known from the genus Achillea, compound 3 is a new natural
product, to the best of our knowledge. All isolated alkamides were tested in
vitro for antiprotozoal activity against Plasmodium falciparum,
Trypanosomabruceirhodesiense, Trypanosomacruzi, and Leishmaniadonovani and for
cytotoxicity against L6 rat skeletal myoblasts.
PMID- 28498320
TI - Chronic Kidney Disease and Exposure to Nephrotoxic Metals.
AB - Chronic kidney disease (CKD) is a common progressive disease that is typically
characterized by the permanent loss of functional nephrons. As injured nephrons
become sclerotic and die, the remaining healthy nephrons undergo numerous
structural, molecular, and functional changes in an attempt to compensate for the
loss of diseased nephrons. These compensatory changes enable the kidney to
maintain fluid and solute homeostasis until approximately 75% of nephrons are
lost. As CKD continues to progress, glomerular filtration rate decreases, and
remaining nephrons are unable to effectively eliminate metabolic wastes and
environmental toxicants from the body. This inability may enhance mortality
and/or morbidity of an individual. Environmental toxicants of particular concern
are arsenic, cadmium, lead, and mercury. Since these metals are present
throughout the environment and exposure to one or more of these metals is
unavoidable, it is important that the way in which these metals are handled by
target organs in normal and disease states is understood completely.
PMID- 28498325
TI - The Health Risk of Cd Released from Low-Cost Jewelry.
AB - The composition of the surface layer of 13 low-cost jewelry samples with a high
Cd content was analyzed using an energy-dispersive X-ray fluorescence
spectrometer (ED XRF). The analyzed jewels were obtained in cooperation with the
Czech Environmental Inspectorate. The jewels were leached in two types of
artificial sweat (acidic and alkaline) for 7 days. Twenty microliters of the
resulting solution was subsequently placed on a paper carrier and analyzed by an
LIBS (Laser-Induced Breakdown Spectrometry) spectrometer after drying. The Cd
content in the jewelry surface layer detected by using ED XRF ranged from 13.4%
to 44.6% (weight per weight-w/w). The samples were subsequently leached in
artificial alkaline, and the acidic sweat and leachates were analyzed using laser
induced breakdown spectrometry (LIBS). The amount of released Cd into alkaline
sweat ranged from 24.0 to 370 ug Cd per week, respectively 3.23-61.7 ug/cm2/week.
The amount of released Cd into acidic sweat ranged from 16.4 to 1517 ug Cd per
week, respectively 3.53-253 ug/cm2/week. The limit of Cd for dermal exposure is
not unequivocally determined in the countries of the EU (European Union) or in
the U.S. Based on the US EPA (United States Environmental Protection Agency)
approach used to establish the reference dose (RfD) for Cd contained in food and
information about the bioavailability of Cd after dermal exposure, we assessed
our own value of dermal RfD. The value was compared with the theoretical amount
of Cd, which can be absorbed into the organism from jewelry in contact with the
skin. The calculation was based on the amount of Cd that was released into acidic
and alkaline sweat. The highest amount of Cd was released into acidic sweat,
which represents 0.1% of dermal RfD and into alkaline sweat, 0.5% of dermal RfD.
These results indicate that the analyzed jewelry contains Cd over the limit for
composition of jewelry available within the territory of the EU. The determined
amount of Cd in analyzed jewelry does not, however, pose a threat in terms of
carcinogenic toxic effects.
PMID- 28498328
TI - Multilook SAR Image Segmentation with an Unknown Number of Clusters Using a Gamma
Mixture Model and Hierarchical Clustering.
AB - This paper presents a novel multilook SAR image segmentation algorithm with an
unknown number of clusters. Firstly, the marginal probability distribution for a
given SAR image is defined by a Gamma mixture model (GaMM), in which the number
of components corresponds to the number of homogeneous regions needed to segment
and the spatial relationship among neighboring pixels is characterized by a
Markov Random Field (MRF) defined by the weighting coefficients of components in
GaMM. During the algorithm iteration procedure, the number of clusters is
gradually reduced by merging two components until they are equal to one. For each
fixed number of clusters, the parameters of GaMM are estimated and the optimal
segmentation result corresponding to the number is obtained by maximizing the
marginal probability. Finally, the number of clusters with minimum global energy
defined as the negative logarithm of marginal probability is indicated as the
expected number of clusters with the homogeneous regions needed to be segmented,
and the corresponding segmentation result is considered as the final optimal one.
The experimental results from the proposed and comparing algorithms for simulated
and real multilook SAR images show that the proposed algorithm can find the real
number of clusters and obtain more accurate segmentation results simultaneously.
PMID- 28498327
TI - Structure, Expression, and Functional Analysis of the Hexokinase Gene Family in
Cassava.
AB - Hexokinase (HXK) proteins play important roles in catalyzing hexose
phosphorylation and sugar sensing and signaling. To investigate the roles of HXKs
in cassava tuber root development, seven HXK genes (MeHXK1-7) were isolated and
analyzed. A phylogenetic analysis revealed that the MeHXK family can be divided
into five subfamilies of plant HXKs. MeHXKs were clearly divided into type A
(MeHXK1) and type B (MeHXK2-7) based on their N-terminal sequences. MeHXK1-5 all
had typical conserved regions and similar protein structures to the HXKs of other
plants; while MeHXK6-7 lacked some of the conserved regions. An expression
analysis of the MeHXK genes in cassava organs or tissues demonstrated that MeHXK2
is the dominant HXK in all the examined tissues (leaves, stems, fruits, tuber
phloems, and tuber xylems). Notably, the expression of MeHXK2 and the enzymatic
activity of HXK were higher at the initial and expanding tuber stages, and lower
at the mature tuber stage. Furthermore, the HXK activity of MeHXK2 was identified
by functional complementation of the HXK-deficient yeast strain YSH7.4-3C (hxk1,
hxk2, glk1). The gene expression and enzymatic activity of MeHXK2 suggest that it
might be the main enzyme for hexose phosphorylation during cassava tuber root
development, which is involved in sucrose metabolism to regulate the accumulation
of starch.
PMID- 28498329
TI - Low-Cost Nested-MIMO Array for Large-Scale Wireless Sensor Applications.
AB - In modern communication and radar applications, large-scale sensor arrays have
increasingly been used to improve the performance of a system. However, the
hardware cost and circuit power consumption scale linearly with the number of
sensors, which makes the whole system expensive and power-hungry. This paper
presents a low-cost nested multiple-input multiple-output (MIMO) array, which is
capable of providing O ( 2 N 2 ) degrees of freedom (DOF) with O ( N ) physical
sensors. The sensor locations of the proposed array have closed-form expressions.
Thus, the aperture size and number of DOF can be predicted as a function of the
total number of sensors. Additionally, with the help of time-sequence-phase
weighting (TSPW) technology, only one receiver channel is required for sampling
the signals received by all of the sensors, which is conducive to reducing the
hardware cost and power consumption. Numerical simulation results demonstrate the
effectiveness and superiority of the proposed array.
PMID- 28498326
TI - A Histopathological Scheme for the Quantitative Scoring of Intervertebral Disc
Degeneration and the Therapeutic Utility of Adult Mesenchymal Stem Cells for
Intervertebral Disc Regeneration.
AB - The purpose of this study was to develop a quantitative histopathological scoring
scheme to evaluate disc degeneration and regeneration using an ovine annular
lesion model of experimental disc degeneration. Toluidine blue and Haematoxylin
and Eosin (H&E) staining were used to evaluate cellular morphology: (i) disc
structure/lesion morphology; (ii) proteoglycan depletion; (iii) cellular
morphology; (iv) blood vessel in-growth; (v) cell influx into lesion; and (vi)
cystic degeneration/chondroid metaplasia. Three study groups were examined: 5 * 5
mm lesion; 6 * 20 mm lesion; and 6 * 20 mm lesion plus mesenchymal stem cell
(MSC) treatment. Lumbar intervertebral discs (IVDs) were scored under categories
(i-vi) to provide a cumulative score, which underwent statistical analysis using
STATA software. Focal proteoglycan depletion was associated with 5 * 5 mm annular
rim lesions, bifurcations, annular delamellation, concentric and radial annular
tears and an early influx of blood vessels and cells around remodeling lesions
but the inner lesion did not heal. Similar features in 6 * 20 mm lesions occurred
over a 3-6-month post operative period. MSCs induced a strong recovery in discal
pathology with a reduction in cumulative histopathology degeneracy score from
15.2 to 2.7 (p = 0.001) over a three-month recovery period but no recovery in
carrier injected discs.
PMID- 28498330
TI - Specific MicroRNA Pattern in Colon Tissue of Young Children with Eosinophilic
Colitis.
AB - Eosinophilic colitis (EC) is a common cause of haematochezia in infants and young
children. The exact pathomechanism is not understood, and the diagnosis is
challenging. The role of microRNAs as key class of regulators of mRNA expression
and translation in patients with EC has not been explored. Therefore, the aim of
the present study was to explore the miRNA profile in EC with respect to
eosinophilic inflammation. Patients enrolled in the study (n = 10) had persistent
rectal bleeding, and did not respond to elimination dietary treatment. High
throughput microRNA sequencing was carried out on colonic biopsy specimens of
children with EC (EC: n = 4) and controls (C: n = 4) as a preliminary screening
of the miRNA profile. Based on the next-generation sequencing (NGS) results and
literature data, a potentially relevant panel of miRNAs were selected for further
measurements by real-time reverse transcription (RT)-PCR (EC: n = 14, C: n = 10).
Validation by RT-PCR resulted in significantly altered expression of miR-21, -31,
-99b, -125a, -146a, -184, -221, -223, and -559 compared to controls (p <= 0.05).
Elevation in miR-21, -99b, -146a, -221, and -223 showed statistically significant
correlation to the extent of tissue eosinophilia. Based on our results, we
conclude that the dysregulated miRNAs have a potential role in the regulation of
apoptosis by targeting Protein kinase B/Mechanistic target of rapamycin
(AKT/mTOR)-related pathways in inflammation by modulating Nuclear factor kappa
light-chain-enhancer of activated B cells (NF-kappaB)-related signalling and
eosinophil cell recruitment and activation, mainly by regulating the expression
of the chemoattractant eotaxin and the adhesion molecule CD44. Our results could
serve as a basis for further extended research exploring the pathomechanism of
EC.
PMID- 28498332
TI - Design, Synthesis, Molecular Docking Analysis, and Carbonic Anhydrase IX
Inhibitory Evaluations of Novel N-Substituted-beta-d-Glucosamine Derivatives that
Incorporate Benzenesulfonamides.
AB - A series of novel N-substituted-beta-d-glucosamine derivatives that incorporate
benzenesulfonamides were designed using a fragment-based drug design strategy.
Each derivative was synthesized and evaluated in vitro for its inhibitory
activity against human carbonic anhydrase (hCA) IX; several derivatives displayed
desirable potency profiles against this enzyme. The molecular docking studies
provided the design rationale and predicted potential binding modes for carbonic
anhydrase (CA) IX and three target compounds, including the most potent
inhibitor, compound 7f (IC50 = 10.01 nM). Moreover, the calculated Log P (cLog P)
values showed that all the compounds tended to be hydrophilic. In addition,
topological polar surface area (TPSA) value-based predictions highlighted the
selectivity of these carbohydrate-based inhibitors for membrane-associated CA IX.
PMID- 28498331
TI - The Roles of Glutamine in the Intestine and Its Implication in Intestinal
Diseases.
AB - Glutamine, the most abundant free amino acid in the human body, is a major
substrate utilized by intestinal cells. The roles of glutamine in intestinal
physiology and management of multiple intestinal diseases have been reported. In
gut physiology, glutamine promotes enterocyte proliferation, regulates tight
junction proteins, suppresses pro-inflammatory signaling pathways, and protects
cells against apoptosis and cellular stresses during normal and pathologic
conditions. As glutamine stores are depleted during severe metabolic stress
including trauma, sepsis, and inflammatory bowel diseases, glutamine
supplementation has been examined in patients to improve their clinical outcomes.
In this review, we discuss the physiological roles of glutamine for intestinal
health and its underlying mechanisms. In addition, we discuss the current
evidence for the efficacy of glutamine supplementation in intestinal diseases.
PMID- 28498334
TI - Pastoralism versus Agriculturalism-How Do Altered Land-Use Forms Affect the
Spread of Invasive Plants in the Degraded Mutara Rangelands of North-Eastern
Rwanda?
AB - Lantana camara L. (Verbenaceae) originates from tropical Central and South
America and has become invasive in about 50 countries. It causes problems when
invading rangelands due to its toxicity to livestock and its tendency to form
dense, monotonous thickets. Its invasiveness can partly be explained by the high
tannin content largely protecting the species from being browsed, its tolerance
to a wide range of environmental conditions, as well as its general preference
for anthropogenically disturbed habitats. The dispersal of L. camara is
facilitated by birds and other animals consuming its drupes (endozoochory), and
so both wild and domestic ungulates could contribute to its spread. In our study,
we investigated the distribution of L. camara in the Mutara rangelands of north
eastern Rwanda, an area that faced dramatic landscape changes in recent decades.
We assessed 23 ecological factors and factors related to land-use and
conservation-political history. Major effects on the local abundance of L. camara
were found in that the relative canopy cover of L. camara was negatively
correlated with the occurrence of other shrubs (suggesting competition for space
and nutrients), while encounter rates of houses, 'living fences' (Euphorbia
tirucalli L.) and cattle tracks were positively correlated with L. camara cover.
Hence, the spread of non-native L. camara in the Mutara rangelands appears to be
linked to landscape alterations arising from the transformation of rangelands
supporting traditional pastoralist communities to other agricultural land-use
forms.
PMID- 28498333
TI - Hypervalent Iodine Reagents in High Valent Transition Metal Chemistry.
AB - Over the last 20 years, high valent metal complexes have evolved from mere
curiosities to being at the forefront of modern catalytic method development.
This approach has enabled transformations complimentary to those possible via
traditional manifolds, most prominently carbon-heteroatom bond formation. Key to
the advancement of this chemistry has been the identification of oxidants that
are capable of accessing these high oxidation state complexes. The oxidant has to
be both powerful enough to achieve the desired oxidation as well as provide
heteroatom ligands for transfer to the metal center; these heteroatoms are often
subsequently transferred to the substrate via reductive elimination. Herein we
will review the central role that hypervalent iodine reagents have played in this
aspect, providing an ideal balance of versatile reactivity, heteroatom ligands,
and mild reaction conditions. Furthermore, these reagents are environmentally
benign, non-toxic, and relatively inexpensive compared to other inorganic
oxidants. We will cover advancements in both catalysis and high valent complex
isolation with a key focus on the subtle effects that oxidant choice can have on
reaction outcome, as well as limitations of current reagents.
PMID- 28498335
TI - The Selective Centrifugation Ensures a Better In Vitro Isolation of ASCs and
Restores a Soft Tissue Regeneration In Vivo.
AB - Autologous fat grafting procedures in plastic surgery have been extensively used
to reinforce soft tissue in congenital or acquired tissue impairments. With this
background, the aim of this study is firstly to examine the impact of a selective
centrifugation on existing adipose stem cells (ASCs) in terms of stemness profile
maintenance and, secondly, to investigate the effect of restoring volume in
reconstruction on patients affected by soft tissue damage. After centrifugation,
the fat graft products were separated into two layers and subsequently examined
in vitro for the expression of CD34, CD90, CD117, CD105, CD29, CD31, CD44, CD73,
CD133, CD14 and CD45 markers by flow cytometry and gene expression analyses were
performed for Sox2, WNT3A, END, CD44, FUT4, COLL1, CTNNB1, hbEGF, KRTLG, MMP2 and
VIM genes. The results showed that in the middle-high density (MHD) layer there
was a peak concentration of ASCs, compared to another layer obtained after
centrifugation. Research carried out on patients under treatment for soft tissue
regeneration using cells obtained from MHD layer selection will be fundamental in
comparative analysis. These studies will lead to an adequate standardization of
outcomes, provided that treatment is performed through cell selection. Therefore,
a unique procedure in tissue reconstruction and regeneration through fat grafting
is presented here.
PMID- 28498336
TI - 11C-Labeling of Aryl Ketones as Candidate Histamine Subtype-3 Receptor PET
Radioligands through Pd(0)-Mediated 11C-Carbonylative Coupling.
AB - Pd(0)-mediated coupling between iodoarenes, [11C]carbon monoxide and
aryltributylstannanes has been used to prepare simple model [11C]aryl ketones.
Here, we aimed to label four 2-aminoethylbenzofuran chemotype based molecules
([11C]1-4) in the carbonyl position, as prospective positron emission tomography
(PET) radioligands for the histamine subtype 3 receptor (H3R) by adapting this
methodology with use of aryltrimethylstannanes. Radiosynthesis was successfully
performed on a platform equipped with a mini-autoclave and a liquid handling
robotic arm, within a lead-shielded hot-cell. Candidate radioligands were readily
formulated in saline containing ethanol (10%, v/v) and ascorbic acid (0.5 mg/10
mL). Yields for preclinical use were in the range of 5-9%, decay-corrected from
cyclotron-produced [11C]CO2 and molar activities were >115 GBq/umol at end of
synthesis. Radiochemical purities exceeded >97%.
PMID- 28498337
TI - Imaging of Early Response to Predict Prognosis in the First-Line Management of
Follicular Non-Hodgkin Lymphoma with Iodine-131-Rituximab Radioimmunotherapy.
AB - The purpose of this study was to evaluate prediction of prognosis after first
line radioimmunotherapy (RIT) of advanced follicular non-Hodgkin lymphoma (FL),
by imaging with fluorine-18-fluorodeoxyglucose positron emission tomography with
computed tomography (18F-FDG-PET/CT) three months after induction treatment by
Iodine-131-rituximab (131I-rituximab). Objective response was determined using
the Deauville 5-point scale in 68 prospective clinical trial patients. Baseline
18F-FDG-PET/CT studies were used to calculate total-metabolic-tumor-volume
(TMTV). Non-imaging studies included the Follicular lymphoma international
prognostic index (FLIPI) and absolute baseline monocyte and lymphocyte counts.
Patients were monitored for over ten years (median follow-up 59 months), and no
patient was lost to follow-up. Complete response (CR) of 88% predicted excellent
prognosis with median time-to-next-treatment (TTNT) not yet reached. Those
patients (12%) who failed to achieve CR (Deauville <= 3) on 18F-FDG-PET/CT at
three months had significantly poorer outcomes (p < 0.0001) with a median TTNT of
41 months. Requirement for re-treatment was predicted by FLIPI and absolute
baseline monocyte count but not lymphocyte count. The TTNT was accurately
predicted by 18F-FDG-PET/CT Deauville response at three months following first
line therapy of FL with RIT. Early response demonstrated by imaging does,
therefore, foretell prognosis in the individual FL patients.
PMID- 28498339
TI - Easy and Fast Reconstruction of a 3D Avatar with an RGB-D Sensor.
AB - This paper proposes a new easy and fast 3D avatar reconstruction method using an
RGB-D sensor. Users can easily implement human body scanning and modeling just
with a personal computer and a single RGB-D sensor such as a Microsoft Kinect
within a small workspace in their home or office. To make the reconstruction of
3D avatars easy and fast, a new data capture strategy is proposed for efficient
human body scanning, which captures only 18 frames from six views with a close
scanning distance to fully cover the body; meanwhile, efficient alignment
algorithms are presented to locally align the data frames in the single view and
then globally align them in multi-views based on pairwise correspondence. In this
method, we do not adopt shape priors or subdivision tools to synthesize the
model, which helps to reduce modeling complexity. Experimental results indicate
that this method can obtain accurate reconstructed 3D avatar models, and the
running performance is faster than that of similar work. This research offers a
useful tool for the manufacturers to quickly and economically create 3D avatars
for products design, entertainment and online shopping.
PMID- 28498338
TI - Synthesis, Biological Activity and Preliminary in Silico ADMET Screening of
Polyamine Conjugates with Bicyclic Systems.
AB - Polyamine conjugates with bicyclic terminal groups including quinazoline,
naphthalene, quinoline, coumarine and indole have been obtained and their
cytotoxic activity against PC-3, DU-145 and MCF-7 cell lines was evaluated in
vitro. Their antiproliferative potential differed markedly and depended on both
their chemical structure and the type of cancer cell line. Noncovalent DNA
binding properties of the most active compounds have been examined using ds-DNA
thermal melting studies and topo I activity assay. The promising biological
activity, DNA intercalative binding mode and favorable drug-like properties of
bis(naphthalene-2-carboxamides) make them a good lead for further development of
potential anticancer drugs.
PMID- 28498340
TI - Nutritional Potential of Selected Insect Species Reared on the Island of Sumatra.
AB - Inhabitants of the Indonesian island of Sumatra are faced with the problem of
insufficient food supplies and the consequent risk of undernourishment and health
issues. Edible insects as a traditional and readily available food source could
be part of the solution. The nutritional value of insects depends on many
factors, e.g., species, developmental stage, sex, diet, and climatic conditions.
However, edible insects bred in Sumatra for human consumption have never before
been assessed with regard to their nutritional value. Our study involved analyses
of crude protein, chitin, fat and selected fatty acid contents of giant mealworm
larvae (Zophobas morio), larvae of the common mealworm (Tenebrio molitor) and
nymphs of the field cricket (Gryllus assimilis). Crude protein content in the
samples ranged from 46% to 56%. Highest (35%) and lowest (31%) amounts of fat
were recorded in giant mealworm larvae and larvae of the common mealworm,
respectively. Chitin amounts ranged from 6% to 13%. Based on these values, which
are comparable to those known from other food insects reared in different regions
of the world, the edible species bred in Sumatra could become food sources with a
potential to help stave off hunger and undernourishment.
PMID- 28498342
TI - Income-Related Inequalities in Access to Dental Care Services in Japan.
AB - Background: This study aimed to evaluate whether income-related inequalities in
access to dental care services exist in Japan. Methods: The subjects included
beneficiaries of the National Health Insurance (NHI) in Chiba City, Japan, who
had been enrolled from 1 April 2014 to 31 March 2015. The presence or absence of
dental visits and number of days spent on dental care services during the year
were calculated using insurance claims submitted. Equivalent household income was
calculated using individual income data from 1 January to 31 December 2013,
declared for taxation. Results: Of the 216,211 enrolled subjects, 50.3% had
dental care during the year. Among those with dental visits, the average number
of days (standard deviation) spent on dental care services per year was 7.7
(7.1). Low income was associated with a decreased rate of dental care utilization
regardless of age and sex. However, there was a significant inverse linear
association between the number of days spent on dental care services and income
levels for both sexes. Conclusions: There were income-related inequalities in
access to dental care services, regardless of the age group or sex, within the
Japanese universal health insurance system.
PMID- 28498341
TI - Replication of High Fetal Alcohol Spectrum Disorders Prevalence Rates, Child
Characteristics, and Maternal Risk Factors in a Second Sample of Rural
Communities in South Africa.
AB - Background: Prevalence and characteristics of fetal alcohol syndrome (FAS) and
total fetal alcohol spectrum disorders (FASD) were studied in a second sample of
three South African rural communities to assess change. Methods: Active case
ascertainment focused on children with height, weight and/or head circumference
<=25th centile and randomly-selected children. Final diagnoses were based on
dysmorphology, neurobehavioral scores, and maternal risk interviews. Results:
Cardinal facial features, head circumference, and total dysmorphology scores
differentiated specific FASD diagnostic categories in a somewhat linear fashion
but all FASD traits were significantly worse than those of randomly-selected
controls. Neurodevelopmental delays were significantly worse for children with
FASD than controls. Binge alcohol use was clearly documented as the proximal
maternal risk factor for FASD, and significant distal risk factors were: low body
mass, education, and income; high gravidity, parity, and age at birth of the
index child. FAS rates continue to extremely high in these communities at 9-129
per 1000 children. Total FASD affect 196-276 per 1000 or 20-28% of the children
in these communities. Conclusions: Very high rates of FASD persist in these
general populations where regular, heavy drinking, often in a binge fashion, co
occurs with low socioeconomic conditions.
PMID- 28498343
TI - Anti-Helicobacter pylori Activity of Isocoumarin Paepalantine: Morphological and
Molecular Docking Analysis.
AB - The Helicobacterpylori bacterium is one of the main causes of chronic gastritis,
peptic ulcers, and even gastric cancer. It affects an average of half of the
world population. Its difficult eradication depends upon multi-drug therapy.
Since its classification as a group 1 carcinogenic by International Agency for
Research on Cancer (IARC), the importance of H. pylori eradication has obtained a
novel meaning. There is considerable interest in alternative therapies for the
eradication of H. pylori using compounds from a wide range of natural products.
In the present study, we investigated the antibacterial property of the
isocoumarin paepalantine against H. pylori and it exhibited significant anti-H.
pylori activity at a minimum inhibitory concentration (MIC) of 128 MUg/mL and at
a minimum bactericidal concentration (MBC) of 256 MUg/mL. The scanning electron
microscopy (SEM) revealed significant morphological changes of the bacterial cell
as a response to a sub-MIC of paepalantine, suggesting a penicillin-binding
protein (PBP) inhibition. Computational studies were carried out in order to
study binding modes for paepalantine in PBP binding sites, exploring the active
and allosteric sites. The data from the present study indicates that paepalantine
exhibits significant anti-H. pylori activity, most likely by inhibiting membrane
protein synthesis.
PMID- 28498346
TI - Power Allocation Based on Data Classification in Wireless Sensor Networks.
AB - Limited node energy in wireless sensor networks is a crucial factor which affects
the monitoring of equipment operation and working conditions in coal mines. In
addition, due to heterogeneous nodes and different data acquisition rates, the
number of arriving packets in a queue network can differ, which may lead to some
queue lengths reaching the maximum value earlier compared with others. In order
to tackle these two problems, an optimal power allocation strategy based on
classified data is proposed in this paper. Arriving data is classified into
dissimilar classes depending on the number of arriving packets. The problem is
formulated as a Lyapunov drift optimization with the objective of minimizing the
weight sum of average power consumption and average data class. As a result, a
suboptimal distributed algorithm without any knowledge of system statistics is
presented. The simulations, conducted in the perfect channel state information
(CSI) case and the imperfect CSI case, reveal that the utility can be pushed
arbitrarily close to optimal by increasing the parameter V, but with a
corresponding growth in the average delay, and that other tunable parameters W
and the classification method in the interior of utility function can trade power
optimality for increased average data class. The above results show that data in
a high class has priorities to be processed than data in a low class, and energy
consumption can be minimized in this resource allocation strategy.
PMID- 28498345
TI - Effects of Long-Chain Omega-3 Polyunsaturated Fatty Acids on Endothelial
Vasodilator Function and Cognition-Are They Interrelated?
AB - Long-chain omega-3 polyunsaturated fatty acids (LCn-3 PUFA) may improve brain
functions by acting on endothelial cells in the cerebrovasculature to facilitate
vasodilatation and perfusion. The aim of this review is to explore this
hypothesis by analyzing the effect of LCn-3 PUFA supplementation on systemic
vasodilator and cognitive function and finding evidence to link LCn-3 PUFA
intake, vasodilator function and cognition. Forty randomized controlled trials
examining the effect of LCn-3 PUFA supplementation in humans on either
endothelial vasodilator function or cognition were identified and pooled effects
measured with a weighted analysis. Compared to placebo, LCn-3 PUFA tended to
increase flow-mediated dilatation and significantly improved cognitive function.
Emerging evidence links vasodilator dysfunction to cognitive impairment, but
evidence that LCn-3 PUFA can improve cognition through enhancements of
vasodilator function is still lacking. Further research is needed to determine:
(1) whether LCn-3 PUFA can enhance dilatation of cerebral vessels; (2) if
improvements in cerebrovascular responsiveness by LCn-3 PUFA are accompanied by
cognitive benefits; and (3) the target population groups.
PMID- 28498344
TI - Mercury in Children: Current State on Exposure through Human Biomonitoring
Studies.
AB - Mercury (Hg) in children has multiple exposure sources and the toxicity of Hg
compounds depends on exposure routes, dose, timing of exposure, and developmental
stage (be it prenatal or postnatal). Over the last decades, Hg was widely
recognized as a threat to the children's health and there have been
acknowledgements at the international level of the need of a global policy
intervention-like the Minamata treaty-aimed at reducing or preventing Hg exposure
and protecting the child health. National human biomonitoring (HBM) data has
demonstrated that low levels of exposure of Hg are still an important health
concern for children, which no one country can solve alone. Although independent
HBM surveys have provided the basis for the achievements of exposure mitigation
in specific contexts, a new paradigm for a coordinated global monitoring of
children's exposure, aimed at a reliable decision-making tool at global level is
yet a great challenge for the next future. The objective of the present review is
to describe current HBM studies on Hg exposure in children, taking into account
the potential pathways of Hg exposure and the actual Hg exposure levels assessed
by different biomarkers.
PMID- 28498347
TI - Wireless Sensor Network-Based Service Provisioning by a Brokering Platform.
AB - This paper proposes a business model for providing services based on the Internet
of Things through a platform that intermediates between human users and Wireless
Sensor Networks (WSNs). The platform seeks to maximize its profit through posting
both the price charged to each user and the price paid to each WSN. A complete
analysis of the profit maximization problem is performed in this paper. We show
that the service provider maximizes its profit by incentivizing all users and all
Wireless Sensor Infrastructure Providers (WSIPs) to join the platform. This is
true not only when the number of users is high, but also when it is moderate,
provided that the costs that the users bear do not trespass a cost ceiling. This
cost ceiling depends on the number of WSIPs, on the value of the intrinsic value
of the service and on the externality that the WSIP has on the user utility.
PMID- 28498349
TI - Desalted Duck Egg White Peptides Promote Calcium Uptake and Modulate Bone
Formation in the Retinoic Acid-Induced Bone Loss Rat and Caco-2 Cell Model.
AB - Desalted duck egg white peptides (DPs) have been proven to promote calcium uptake
in Caco-2 cells and rats treated with a calcium-deficient diet. The retinoic acid
induced bone loss model was used to evaluate the effect of DPs on calcium
absorption and bone formation. Three-month-old Wistar female rats were treated
with 0.9% saline, DPs (800 mg/kg), or alendronate (5 mg/kg) for three weeks
immediately after retinoic acid treatment (80 mg/kg) once daily for two weeks.
The model group was significantly higher in serum bone alkaline phosphatase than
the other three groups (p < 0.05), but lower in calcium absorption rate, serum
osteocalcin, bone weight index, bone calcium content, bone mineral density, and
bone max load. After treatment with DPs or alendronate, the absorption rate
increased and some serum and bone indices recovered. The morphology results
indicated bone tissue form were ameliorated and numbers of osteoclasts decreased
after supplementation with DPs or alendronate. The in vitro study showed that the
transient receptor potential vanilloid 6 (TRPV6) calcium channel was the main
transport pathway of both DPs and Val-Ser-Glu-Glu peptitde (VSEE), which was
identified from DPs. Our results indicated that DPs could be a promising
alternative to current therapeutic agents for bone loss because of the promotion
of calcium uptake and regulation of bone formation.
PMID- 28498350
TI - Comparison of Direct Sequencing, Real-Time PCR-High Resolution Melt (PCR-HRM) and
PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) Analysis for Genotyping
of Common Thiopurine Intolerant Variant Alleles NUDT15 c.415C>T and TPMT c.719A>G
(TPMT*3C).
AB - Thiopurine intolerance and treatment-related toxicity, such as fatal
myelosuppression, is related to non-function genetic variants encoding thiopurine
S-methyltransferase (TPMT) and Nudix hydrolase 15 (NUDT15). Genetic testing of
the common variants NUDT15:NM_018283.2:c.415C>T (Arg139Cys, dbSNP rs116855232 T
allele) and TPMT: NM_000367.4:c.719A>G (TPMT*3C, dbSNP rs1142345 G allele) in
East Asians including Chinese can potentially prevent treatment-related
complications. Two complementary genotyping approaches, real-time PCR-high
resolution melt (PCR-HRM) and PCR-restriction fragment length morphism (PCR-RFLP)
analysis were evaluated using conventional PCR and Sanger sequencing genotyping
as the gold standard. Sixty patient samples were tested, revealing seven patients
(11.7%) heterozygous for NUDT15 c.415C>T, one patient homozygous for the variant
and one patient heterozygous for the TPMT*3C non-function allele. No patient was
found to harbor both variants. In total, nine out of 60 (15%) patients tested had
genotypic evidence of thiopurine intolerance, which may require dosage adjustment
or alternative medication should they be started on azathioprine, mercaptopurine
or thioguanine. The two newly developed assays were more efficient and showed
complete concordance (60/60, 100%) compared to the Sanger sequencing results.
Accurate and cost-effective genotyping assays by real-time PCR-HRM and PCR-RFLP
for NUDT15 c.415C>T and TPMT*3C were successfully developed. Further studies may
establish their roles in genotype-informed clinical decision-making in the
prevention of morbidity and mortality due to thiopurine intolerance.
PMID- 28498348
TI - Nutrients Turned into Toxins: Microbiota Modulation of Nutrient Properties in
Chronic Kidney Disease.
AB - In chronic kidney disease (CKD), accumulation of uremic toxins is associated with
an increased risk of death. Some uremic toxins are ingested with the diet, such
as phosphate and star fruit-derived caramboxin. Others result from nutrient
processing by gut microbiota, yielding precursors of uremic toxins or uremic
toxins themselves. These nutrients include l-carnitine,
choline/phosphatidylcholine, tryptophan and tyrosine, which are also sold over
the-counter as nutritional supplements. Physicians and patients alike should be
aware that, in CKD patients, the use of these supplements may lead to potentially
toxic effects. Unfortunately, most patients with CKD are not aware of their
condition. Some of the dietary components may modify the gut microbiota,
increasing the number of bacteria that process them to yield uremic toxins, such
as trimethylamine N-Oxide (TMAO), p-cresyl sulfate, indoxyl sulfate and indole-3
acetic acid. Circulating levels of nutrient-derived uremic toxins are associated
to increased risk of death and cardiovascular disease and there is evidence that
this association may be causal. Future developments may include maneuvers to
modify gut processing or absorption of these nutrients or derivatives to improve
CKD patient outcomes.
PMID- 28498351
TI - Low Family Support and Risk of Obesity among Black Youth: Role of Gender and
Ethnicity.
AB - : Most studies on the role of family environment in developing risk of obesity
among youth have focused on parenting behaviors that are directly involved in
energy balance in regional, non-representative White samples. Using a national
sample of ethnically diverse Black youth, the current study tested the
association between low family support and risk of obesity. We also tested the
heterogeneity of this association based on gender, ethnicity, and their
intersection. We used data from the National Survey of American Life-Adolescent
Supplement (NSAL-A), a national survey of Black adolescents in the United States.
The study enrolled 1170 African American and Caribbean Black 13-17 year old
youth. Obesity was defined based on the cutoff points of body mass index (BMI)
appropriate for age and gender of youth. Family support was measured using a five
item measure that captured emotional and tangible social support. Age, gender,
and ethnicity were also measured. Logistic regressions were utilized in the
pooled sample, and also based on gender, ethnicity, and their intersection, to
test the link between low family support and risk for obesity. RESULTS: In the
pooled sample, low family support was not associated with an increased risk of
obesity (OR = 1.35, 95% Confidence Interval (CI) = 0.96-1.89). The association
between low family support and risk of obesity was, however, significant among
African American females (OR = 1.60, 95% CI = 1.01-2.55). There was no
association for African American males (OR = 1.26, 95% CI = 0.82-1.92), Caribbean
Black males (OR = 0.68, 95% CI = 0.01-54.85), and Caribbean Black females (OR =
0.78, 95% CI = 0.42-1.44). In conclusion, policies and programs that enable
African American families to provide additional family support may prevent
obesity among African American female youth. Future research should test the
efficacy of promoting family support as a tool for preventing obesity among
African American female youth.
PMID- 28498352
TI - Encapsulation of 16-Hydroxycleroda-3,13-Dine-16,15-Olide in Mesoporous Silica
Nanoparticles as a Natural Dipeptidyl Peptidase-4 Inhibitor Potentiated
Hypoglycemia in Diabetic Mice.
AB - Natural supplements comprise good efficacy with less adverse effects as against
diabetic therapy, but their advancement as anti-diabetic agents is unsatisfactory
with regard to the delivery system. Dipeptidyl peptidase-4 (DPP4)/CD26) can
degrade glucagon-like pepetide-1 (GLP-1) which renders a decrease of blood
glucose levels. 16-hydroxycleroda-3,13-dine-16,15-olide (HCD) extracted from
Polyalthia longifolia, exhibits numerous medicinal potentials including
hypoglycemic potential. On consideration of HCD application, the bioavailability
is affected by low solubility. Extended experiments of anti-diabetic efficacy
confirmed HCD biocompatible with mesoporous silica nanoparticles (MSNs)
encapsulation resulted in a sustained release property in delivering HCD for the
inhibition of DPP4 via the activity and protein levels of DPP4 analysis. In the
enzymatic activity assay, MSN-HCD directly changed DPP4 activity. Moreover, MSN
HCD nanoparticles were treated with Caco-2 cells and the protein levels of DPP4
determined within the cells. The results revealed that MSN-HCD caused reduction
of DPP4 activity in a time- and dose-dependent fashion. Orally administered MSN
HCD in diet-induced diabetic mice alleviated blood glucose via an oral glucose
tolerance test. In addition, administration of MSN-HCD for five weeks revealed
that the biochemical cues such as pyruvate transaminase (GPT), glutamate
oxaloacetate transaminase (GOT), triglycerides (TG), cholesterol (CHO), and
glycated hemoglobin (HbA1c) in mice were commendable as further confirmation of
MSN-HCD efficacy and less adverse effects in down-regulation of hyperglycemia.
Furthermore, this formulation effectively controlled blood glucose and
significantly decreased the body weight of mice, suggesting that MSN-HCD exerts
natural DPP4 inhibitor as a potential clinical drug for the treatment of
diabetes.
PMID- 28498353
TI - HepPar1-Positive Circulating Microparticles Are Increased in Subjects with
Hepatocellular Carcinoma and Predict Early Recurrence after Liver Resection.
AB - Circulating microparticles (MPs) are novel potential biomarkers in cancer
patients. Their role in hepatocellular carcinoma (HCC) is under intensive
investigation. In this study, we tested the hypothesis that MPs expressing the
antigen HepPar1 are increased in the blood of subjects with HCC and may serve as
markers of early recurrence after liver resection (LR). We studied 15 patients
affected by HCC undergoing LR, and used flow cytometry to assess the number of
circulating HepPar1+ MPs. Ten subjects without HCC (five with liver cirrhosis and
five with healthy livers) were used as controls. After LR, HCC patients underwent
a follow-up to check for early recurrence, which occurred in seven cases. The
number of circulating HepPar1+ MPs was significantly higher in subjects affected
by HCC, compared to individuals without cancer (p < 0.01). We also found that,
among HCC patients, the number of circulating HepPar1+ MPs, measured before LR,
was significantly higher in those who displayed early recurrence compared to
those without recurrence (p = 0.02). Of note, other types of circulating MPs,
such as those derived from endothelial cells (CD144+) or those produced by the
activated endothelium (CD144+/CD62+), were not associated with HCC, nor could
they predict HCC recurrence. HepPar1+ MPs deserve further investigation as novel
biomarkers of disease and prognosis in HCC patients.
PMID- 28498354
TI - Ortho-Nitro Effect on the Diastereoselective Control in Sulfa-Staudinger and
Staudinger Cycloadditions.
AB - The ortho-nitro effect was discovered in sulfa-Staudinger cycloadditions of
ethoxycarbonylsulfene with linear imines. When an ortho-nitro group is present at
the C-aryl substituents of linear imines, the sulfa-Staudinger cycloadditions
deliver cis-beta-sultams in considerable amounts, together with the predominant
trans-beta-sultams. In other cases, the above sulfa-Staudinger cycloadditions
give rise to trans-beta-sultams exclusively. Further mechanistic rationalization
discloses that the ortho-nitro effect is attributed to its strong electron
withdrawing inductive effect. Similarly, the ortho-nitro effect also exists in
Staudinger cycloadditions of ethoxycarbonyl ketene with the imines. The current
research provides further insights into the diastereoselective control in sulfa
Staudinger and Staudinger cycloadditions.
PMID- 28498355
TI - The Link between Mastery and Depression among Black Adolescents; Ethnic and
Gender Differences.
AB - PURPOSE: Although the link between depression and lower levels of mastery is well
established, limited information exists on ethnic and gender differences in the
association between the two. The current study investigated ethnic, gender, and
ethnic by gender differences in the link between major depressive disorder (MDD)
and low mastery in the United States. METHODS: We used data from the National
Survey of American Life-Adolescent supplement (NSAL-A), 2003-2004. In total, 1170
Black adolescents entered the study. This number was composed of 810 African
American and 360 Caribbean Black youth (age 13 to 17). Demographic factors,
socioeconomic status (family income), mastery (sense of control over life), and
MDD (Composite International Diagnostic Interview, CIDI) were measured. Logistic
regressions were used to test the association between mastery and MDD in the
pooled sample, as well as based on ethnicity and gender. RESULTS: In the pooled
sample, a higher sense of mastery was associated with a lower risk of MDD. This
association, however, was significant for African Americans but not Caribbean
Blacks. Similarly, among African American males and females, higher mastery was
associated with lower risk of MDD. Such association could not be found for
Caribbean Black males or females. CONCLUSION: Findings indicate ethnic rather
than gender differences in the association between depression and mastery among
Black youth. Further research is needed to understand how cultural values and
life experiences may alter the link between depression and mastery among
ethnically diverse Black youth.
PMID- 28498356
TI - Nine Different Chemical Species and Action Mechanisms of Pancreatic Lipase
Ligands Screened Out from Forsythia suspensa Leaves All at One Time.
AB - It is difficult to screen out as many active components as possible from natural
plants all at one time. In this study, subfractions of Forsythia suspensa leaves
were firstly prepared; then, their inhibitive abilities on pancreatic lipase were
tested; finally, the highest inhibiting subfraction was screened by self-made
immobilized pancreatic lipase. Results showed that nine ligands, including eight
inhibitors and one promotor, were screened out all at one time. They were three
flavonoids (rutin, IC50: 149 +/- 6.0 MUmol/L; hesperidin, 52.4 MUmol/L;
kaempferol-3-O-rutinoside, isolated from F. suspensa leaves for the first time,
IC50 notably reached 2.9 +/- 0.5 MUmol/L), two polyphenols (chlorogenic acid,
3150 +/- 120 MUmol/L; caffeic acid, 1394 +/- 52 MUmol/L), two lignans (phillyrin,
promoter; arctigenin, 2129 +/- 10.5 MUmol/L), and two phenethyl alcohol
(forsythiaside A, 2155 +/- 8.5 MUmol/L; its isomer). Their action mechanisms
included competitive inhibition, competitive promotion, noncompetitive
inhibition, and uncompetitive inhibition. In sum, using the appropriate methods,
more active ingredients can be simply and quickly screened out all at one time
from a complex natural product system. In addition, F. suspensa leaves contain
numerous inhibitors of pancreatic lipase.
PMID- 28498358
TI - Three New Indole Diterpenoids from the Sea-Anemone-Derived Fungus Penicillium sp.
AS-79.
AB - Three new indolediterpenoids, namely, 22-hydroxylshearinine F (1), 6
hydroxylpaspalinine (2), and 7-O-acetylemindole SB (3), along with eight related
known analogs (4-11), were isolated from the sea-anemone-derived fungus
Penicillium sp. AS-79. The structures and relative configurations of these
compounds were determined by a detailed interpretation of the spectroscopic data,
and their absolute configurations were determined by ECD calculations (1 and 2)
and single-crystal X-ray diffraction (3). Some of these compounds exhibited
prominent activity against aquatic and human pathogenic microbes.
PMID- 28498357
TI - Adiponectin Is Involved in Connective Tissue Growth Factor-Induced Proliferation,
Migration and Overproduction of the Extracellular Matrix in Keloid Fibroblasts.
AB - Adiponectin, an adipocyte-derived hormone, exerts pleiotropic biological effects
on metabolism, inflammation, vascular homeostasis, apoptosis and immunity.
Recently, adiponectin has been suggested to attenuate the progression of human
dermal fibrosis. Connective tissue growth factor (CTGF) is induced in keloids and
is thought to be participated in the formation of keloid fibrosis. However, the
roles played by adiponectin in keloids remain unclear. In this study, we explored
the effects of adiponectin on CTGF-induced cell proliferation, migration and the
deposition of extracellular matrix (ECM) and their associated intracellular
signalling pathways in keloid fibroblasts (KFs). We also explored possible
mechanisms of keloid pathogenesis. Primary fibroblast cultures were established
from foreskin biopsies and skin biopsies from patients with keloids. The
expression of adiponectin and adiponectin receptors (adipoRs) was evaluated by
reverse transcription-PCR (RT-PCR), quantitative real-time RT-PCR,
immunofluorescence staining, and immunohistochemical analysis. Next, KFs and
normal dermal fibroblasts (NFs) were treated with CTGF in the presence or absence
of adiponectin. A cell counting kit-8 (CCK-8) and the Transwell assay were used
to examine cell proliferation and migration. The level of the collagen I,
fibronectin (FN) and alpha-smooth muscle actin (alpha-SMA) mRNAs and proteins
were determined by quantitative real-time RT-PCR and western blotting. The
effects of RNA interference (RNAi) targeting the adipoR genes were detected.
Phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase
(AMPK), mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 kinase
protein kinase (PI3K-Akt) were examined by western blotting to further
investigate the signalling pathways. Furthermore, inhibitors of signal
transduction pathways were investigated. The expression levels of adiponectin and
adipoRs were significantly decreased in keloids compared with those in normal
skin tissue. Adiponectin suppressed the CTGF-induced KFs, but not NFs,
proliferation, migration and ECM production. Moreover, adiponectin inhibited the
phosphorylation of AMPK, p38 and extracellular-regulated kinase (ERK), but not
that of Jun N-terminal kinase (JNK) or Akt, in CTGF-treated KFs. The activity of
adiponectin-mediated signalling pathways was attenuated by small interfering RNAs
(siRNAs) targeting adipoR1 (but not siRNAs targeting adipoR2, T-cadherin or
calreticulin), AMPK (Compound C), p38 (SB203580) inhibitors, and mitogen
activated protein kinase kinase (MEK) inhibitor (PD98059). Based on our results,
adiponectin suppresses CTGF-induced KFs proliferation, migration and ECM
overproduction. One of the underlying mechanisms is the activation of the
adipoR1, AMPK, p38, and ERK signalling pathways. Therefore, adiponectin may play
an important role in the progression of keloids, suggesting a potential novel
target for keloid treatment.
PMID- 28498359
TI - Assessing the Risk of Hg Exposure Associated with Rice Consumption in a Typical
City (Suzhou) in Eastern China.
AB - Recent studies have revealed that not only fish but also rice consumption may
significantly contribute to human exposure to mercury (Hg) in Asian countries. It
is therefore essential to assess dietary exposure to Hg in rice and its
associated health risk. However, risk assessments of Hg in rice in non
contaminated areas are generally lacking in Asian countries. In the present
study, Hg concentrations were measured in rice samples collected from markets and
supermarkets in Suzhou, a typical city in Eastern China. In addition, the rice
ingestion rates (IR) were assessed via a questionnaire-based survey of Suzhou
residents. The data were then used to assess the risk of Hg exposure associated
with rice consumption, by calculating the hazard quotient (HQ). Hg contents in
rice samples were well below the national standard (20 MUg/kg), ranging from 1.46
to 8.48 ng/g. They were also significantly (p > 0.05) independent of the area of
production and place of purchase (markets vs. supermarkets in the different
districts). Our results indicate a low risk of Hg exposure from rice in Suzhou
(HQ: 0.005-0.05), despite the generally high personal IR (0.05-0.4 kg/day). The
risk of Hg associated with rice consumption for Suzhou residents was not
significantly affected by the age or sex of the consumer (p > 0.05). Overall, our
results provide a study of human exposure to Hg in rice in Chinese cities not
known to be contaminated with Hg. Future studies should examine Hg exposure in
different areas in China and in potentially vulnerable major food types.
PMID- 28498361
TI - Rectal Cancer in a Patient with Bartter Syndrome: A Case Report.
AB - A woman with rectal cancer was scheduled for surgery. However, she also had
hypokalemia, hyperreninemia, and hyperaldosteronism in the absence of any known
predisposing factors or endocrine tumors. She was given intravenous potassium,
and her blood abnormalities stabilized after tumor resection. Genetic analysis
revealed mutations in several genes associated with Bartter syndrome (BS) and
Gitelman syndrome, including SLC12A1, CLCNKB, CASR, SLC26A3, and SLC12A3.
Prostaglandin E2 (PGE2) plays an important role in BS and worsens electrolyte
abnormalities. The PGE2 level is reportedly increased in colorectal cancer, and
in the present case, immunohistochemical examination revealed an increased PGE2
level in the tumor. We concluded that the tumor-related PGE2 elevation had
worsened the patient's BS, which became more manageable after tumor resection.
PMID- 28498360
TI - Meristem Plant Cells as a Sustainable Source of Redox Actives for Skin
Rejuvenation.
AB - Recently, aggressive advertisement claimed a "magic role" for plant stem cells in
human skin rejuvenation. This review aims to shed light on the scientific
background suggesting feasibility of using plant cells as a basis of anti-age
cosmetics. When meristem cell cultures obtained from medicinal plants are exposed
to appropriate elicitors/stressors (ultraviolet, ultrasound ultraviolet (UV),
ultrasonic waves, microbial/insect metabolites, heavy metals, organic toxins,
nutrient deprivation, etc.), a protective/adaptive response initiates the
biosynthesis of secondary metabolites. Highly bioavailable and biocompatible to
human cells, low-molecular weight plant secondary metabolites share
structural/functional similarities with human non-protein regulatory hormones,
neurotransmitters, pigments, polyamines, amino-/fatty acids. Their redox
regulated biosynthesis triggers in turn plant cell antioxidant and detoxification
molecular mechanisms resembling human cell pathways. Easily isolated in
relatively large quantities from contaminant-free cell cultures, plant
metabolites target skin ageing mechanisms, above all redox imbalance. Perfect
modulators of cutaneous oxidative state via direct/indirect antioxidant action,
free radical scavenging, UV protection, and transition-metal chelation, they are
ideal candidates to restore photochemical/redox/immune/metabolic barriers,
gradually deteriorating in the ageing skin. The industrial production of plant
meristem cell metabolites is toxicologically and ecologically sustainable for
fully "biological" anti-age cosmetics.
PMID- 28498362
TI - Caspases and their substrates.
AB - Protease biology is intimately linked to the functional consequences of substrate
cleavage events. Human caspases are a family of 12 fate-determining cysteine
proteases that are best known for driving cell death, either apoptosis or
pyroptosis. More recently, caspases have been shown to be involved in other
cellular remodeling events as well including stem cell fate determination,
spermatogenesis, and erythroid differentiation. Recent global proteomics methods
enable characterization of the substrates that caspases cleave in live cells and
cell extracts. The number of substrate targets identified for individual caspases
can vary widely ranging from only a (few) dozen targets for caspases-4, -5, -9,
and -14 to hundreds of targets for caspases-1, -2, -3, -6, -7, and -8. Proteomic
studies characterizing the rates of target cleavage show that each caspase has a
preferred substrate cohort that sometimes overlaps between caspases, but whose
rates of cleavage vary over 500-fold within each group. Determining the
functional consequences of discrete proteolytic events within the global
substrate pool is a major challenge for the field. From the handful of individual
targets that have been studied in detail, there are only a few so far that whose
single cleavage event is capable of sparking apoptosis alone, such as cleavage of
caspase-3/-7 and BIMEL, or for pyroptosis, gasdermin D. For the most part, it
appears that cleavage events function cooperatively in the cell death process to
generate a proteolytic synthetic lethal outcome. In contrast to apoptosis, far
less is known about caspase biology in non-apoptotic cellular processes, such as
cellular remodeling, including which caspases are activated, the mechanisms of
their activation and deactivation, and the key substrate targets. Here we survey
the progress made in global identification of caspase substrates using proteomics
and the exciting new avenues these studies have opened for understanding the
molecular logic of substrate cleavage in apoptotic and non-apoptotic processes.
PMID- 28498363
TI - A novel microRNA regulator of prostate cancer epithelial-mesenchymal transition.
AB - The most frequent alteration in the prostate oncogenome is loss of chromosome
(chr) 8p21 that has been associated with loss of NKX3.1 homeobox gene. Chr8p21
deletions increase significantly with tumor grade and are associated with poor
prognosis in prostate cancer (PCa), suggesting critical involvement of this
region in tumor progression. Recent studies suggest that apart from NKX3.1, this
region harbors alternative tumor suppressors that are yet undefined. We proposed
a novel, paradigm shifting hypothesis that this locus is associated with a miRNA
gene cluster-miR-3622a/b- that plays a crucial suppressive role in PCa. Here we
demonstrate the crucial role of miR-3622a in prostate cancer epithelial-to
mesenchymal transition (EMT). MicroRNA expression profiling in microdissected
human PCa clinical tissues showed that miR-3622a expression is widely
downregulated and is significantly correlated with poor survival outcome and
tumor progression. To understand the functional significance of miR-3622a,
knockdown and overexpression was performed using non-transformed prostate
epithelial and PCa cell lines, respectively, followed by functional assays. Our
data demonstrate that endogenous miR-3622a expression is vital to maintain the
epithelial state of normal and untransformed prostate cells. miR-3622a expression
inhibits EMT, progression and metastasis of PCa in vitro and in vivo. Further, we
found that miR-3622a directly targets EMT effectors ZEB1 and SNAI2. In view of
these data, we propose that frequent loss of miR-3622a at chr8p21 region leads to
induction of EMT states that in turn, promotes PCa progression and metastasis.
This study has potentially significant implications in the field of prostate
cancer as it identifies an important miRNA component of a frequently lost
chromosomal region with critical roles in prostate carcinogenesis which is a
highly significant step towards understanding the mechanistic involvement of this
locus. Also, our study indicates that miR-3622a is a novel PCa biomarker and
potential drug target for developing therapeutic regimens against advanced PCa.
PMID- 28498364
TI - Convergence of mitochondrial and chloroplastic ANAC017/PAP-dependent retrograde
signalling pathways and suppression of programmed cell death.
AB - The energy-converting organelles mitochondria and chloroplasts are tightly
embedded in cellular metabolism and stress response. To appropriately control
organelle function, extensive regulatory mechanisms are at play that involve two
way exchange between the nucleus and mitochondria/chloroplasts. In recent years,
our understanding of how mitochondria and chloroplasts provide 'retrograde'
feedback to the nucleus, resulting in targeted transcriptional changes, has
greatly increased. Nevertheless, mitochondrial and chloroplast retrograde
signalling have largely been studied independently, and only few points of
interaction have been found or proposed. Through reassessment of recent
publications, this perspective proposes that two of the most well-studied
retrograde signalling pathways in plants, those mediated by ANAC017 and those
mediated by phosphoadenosine phosphate (PAP), are most likely convergent and can
direct overlapping genes. Furthermore, at least part of this common retrograde
response appears targeted towards suppression of programmed cell death (PCD)
triggered by organellar defects. The identified target genes are discussed in
light of their roles in PCD suppression and amplifying the signalling cascade via
positive-feedback loops. Finally, a mechanism is proposed that may explain why
the convergence of PAP/ANAC017-dependent signalling appears capable of
suppressing some types of PCD lesions, but not others, based on the subcellular
location of the initial PCD-inducing dysfunction.
PMID- 28498366
TI - Till stress do us ataRT: a novel toxin-antitoxin system targeting translation
initiation.
PMID- 28498365
TI - Inhibition of Twist1-mediated invasion by Chk2 promotes premature senescence in
p53-defective cancer cells.
AB - Twist1, a basic helix-loop-helix transcription factor is implicated as a key
mediator of epithelial-mesenchymal transition (EMT) and metastatic dissemination
in p53-deficient cancer cells. On the other hand, checkpoint kinase 2 (Chk2), a
major cell cycle regulatory protein provides a barrier to tumorigenesis due to
DNA damage response by preserving genomic stability of the cells. Here we
demonstrate that Chk2 induction proficiently abrogates invasion, cell scattering
and invadopodia formation ability of p53-mutated invasive cells by suppressing
Twist1, indicating Chk2 confers vital role in metastasis prevention. In addition,
ectopic Chk2, as well as its (Chk2) induction by natural podophyllotoxin analog,
4'-demethyl-deoxypodophyllotoxin glucoside (4DPG), strongly restrain Twist1
activity along with other mesenchymal markers, for example, ZEB-1, vimentin and
Snail1, whereas the epithelial markers such as E-cadherin and TIMP-1 expression
augmented robustly. However, downregulation of endogenous Chk2 by siRNA as well
as Chk2 selective inhibitor PV1019 implies that 4DPG-mediated inhibition of
Twist1 is Chk2-dependent. Further, mechanistic studies unveil that Chk2
negatively regulates Twist1 promoter activity and it (Chk2) interacts steadily
with Snail1 protein to curb EMT. Strikingly, Chk2 overexpression triggers
premature senescence in these cells with distinctive increase in senescence
associated beta-galactosidase (SA-beta-gal) activity, G2/M cell cycle arrest and
induction of senescence-specific marker p21waf1/Cip1. Importantly, stable
knockdown of Twist1 by shRNA markedly augments p21 expression, its nuclear
accumulation, senescence-associated heterochromatin foci (SAHF) and amplifies the
number of SA-beta-gal-positive cells. Moreover, our in vivo studies also validate
that 4DPG treatment significantly abrogates tumor growth as well as metastatic
lung nodules formation by elevating the level of phospho-Chk2, Chk2 and
suppressing Twist1 activity in mouse mammary carcinoma model. In a nutshell, this
report conceives a novel strategy of Twist1 suppression through Chk2 induction,
which prevents metastatic dissemination and promotes premature senescence in p53
defective invasive cancer cells.
PMID- 28498368
TI - It is a differentiation game: STAT5 in a new role.
PMID- 28498369
TI - Circular RNA mediates cardiomyocyte death via miRNA-dependent upregulation of
MTP18 expression.
AB - Circular RNAs (circRNAs) have important roles in several cellular processes. No
study has established the pathophysiological role for circRNAs in the heart.
Here, we show that a circRNA (mitochondrial fission and apoptosis-related circRNA
(MFACR)) regulates mitochondrial fission and apoptosis in the heart by directly
targeting and downregulating miR-652-3p; this in turn blocks mitochondrial
fission and cardiomyocyte cell death by suppressing MTP18 translation. MTP18
deficiency reduces mitochondrial fission and suppresses cardiomyocyte apoptosis
and MI. miR-652-3p directly downregulates MTP18 and attenuates mitochondrial
fission, cardiomyocyte apoptosis, and MI in vitro and in vivo. MFACR directly
sequesters miR-652-3p in the cytoplasm and inhibits its activity. MFACR knockdown
in cardiomyocytes and mice attenuates mitochondrial fission and MI. Our results
reveal a crucial role for circRNA in regulating mitochondrial dynamics and
apoptosis in the heart; as such, circRNAs may serve as a potential therapeutic
avenue for cardiovascular diseases.
PMID- 28498367
TI - Initiation and execution mechanisms of necroptosis: an overview.
AB - Necroptosis is a form of regulated cell death, which is induced by ligand binding
to TNF family death domain receptors, pattern recognizing receptors and virus
sensors. The common feature of these receptor systems is the implication of
proteins, which contain a receptor interaction protein kinase (RIPK) homology
interaction motif (RHIM) mediating recruitment and activation of receptor
interacting protein kinase 3 (RIPK3), which ultimately activates the necroptosis
executioner mixed lineage kinase domain-like (MLKL). In case of the TNF family
members, the initiator is the survival- and cell death-regulating RIPK1 kinase,
in the case of Toll-like receptor 3/4 (TLR3/4), a RHIM-containing adaptor, called
TRIF, while in the case of Z-DNA-binding protein ZBP1/DAI, the cytosolic viral
sensor itself contains a RHIM domain. In this review, we discuss the different
protein complexes that serve as nucleation platforms for necroptosis and the
mechanism of execution of necroptosis. Transgenic models (knockout, kinase-dead
knock-in) and pharmacologic inhibition indicate that RIPK1, RIPK3 or MLKL are
implicated in many inflammatory, degenerative and infectious diseases. However,
the conclusion of necroptosis being solely involved in the etiology of diseases
is blurred by the pleiotropic roles of RIPK1 and RIPK3 in other cellular
processes such as apoptosis and inflammasome activation.
PMID- 28498371
TI - Low absolute peripheral blood CD4+ T-cell count predicts poor prognosis in R-CHOP
treated patients with diffuse large B-cell lymphoma.
PMID- 28498370
TI - Validation of response assessment according to international consortium for
MDS/MPN criteria in chronic myelomonocytic leukemia treated with hypomethylating
agents.
PMID- 28498372
TI - Comparative transcriptomics analyses reveal the conservation of an ancestral
infectious strategy in two bacteriophage genera.
AB - Although the evolution of tailed bacteriophages has increasingly been better
understood through comparisons of their DNA sequences, the functional
consequences of this evolution on phage infectious strategies have remained
unresolved. In this study, we comprehensively compared the transcriptional
strategies of two related myoviruses, PAK_P3 and PAK_P4, infecting the same
Pseudomonas aeruginosa host strain. Outside of the conservation of their
structural clusters, their highly syntenic genomes display only limited DNA
similarity. Despite this apparent divergence, we found that both viruses follow a
similar infection scheme, relying on a temporal regulation of their gene
expression, likely involving the use of antisense transcripts, as well as a rapid
degradation of 90% of the host non-ribosomal mRNA, as previously reported for
PAK_P3. However, the kinetics of the mRNA degradation is remarkably faster during
PAK_P4 infection. Moreover, we found that each virus has evolved specific
adaptations, as exemplified by the distinct patterns of their core genes
expression as well as the specific manipulation of the expression of iron-related
host genes by PAK_P4. This study enhances our understanding of the evolutionary
process of virulent phages, which relies on adjusting globally conserved
ancestral infection mechanisms.
PMID- 28498373
TI - Genomic exploration of individual giant ocean viruses.
AB - Viruses are major pathogens in all biological systems. Virus propagation and
downstream analysis remains a challenge, particularly in the ocean where the
majority of their microbial hosts remain recalcitrant to current culturing
techniques. We used a cultivation-independent approach to isolate and sequence
individual viruses. The protocol uses high-speed fluorescence-activated virus
sorting flow cytometry, multiple displacement amplification (MDA), and downstream
genomic sequencing. We focused on 'giant viruses' that are readily
distinguishable by flow cytometry. From a single-milliliter sample of seawater
collected from off the dock at Boothbay Harbor, ME, USA, we sorted almost 700
single virus particles, and subsequently focused on a detailed genome analysis of
12. A wide diversity of viruses was identified that included Iridoviridae,
extended Mimiviridae and even a taxonomically novel (unresolved) giant virus. We
discovered a viral metacaspase homolog in one of our sorted virus particles and
discussed its implications in rewiring host metabolism to enhance infection. In
addition, we demonstrated that viral metacaspases are widespread in the ocean. We
also discovered a virus that contains both a reverse transcriptase and a
transposase; although highly speculative, we suggest such a genetic complement
would potentially allow this virus to exploit a latency propagation mechanism.
Application of single virus genomics provides a powerful opportunity to
circumvent cultivation of viruses, moving directly to genomic investigation of
naturally occurring viruses, with the assurance that the sequence data is virus
specific, non-chimeric and contains no cellular contamination.
PMID- 28498374
TI - Ranibizumab pretreatment in diabetic vitrectomy: a pilot randomised controlled
trial (the RaDiVit study).
AB - PurposeOur aim was to evaluate the impact of intravitreal ranibizumab
pretreatment on the outcome of vitrectomy surgery for advanced proliferative
diabetic retinopathy. The objective was to determine the feasibility of a
subsequent definitive trial and estimate the effect size and variability of the
outcome measure.Patients and methodsWe performed a pilot randomised double-masked
single-centre clinical trial in 30 participants with tractional retinal
detachment associated with proliferative diabetic retinopathy. Seven days prior
to vitrectomy surgery, participants were randomly allocated to receive either
intravitreal ranibizumab (Lucentis, Novartis Pharmaceuticals UK Ltd, Frimley, UK)
or subconjunctival saline (control). The primary outcome was best-corrected
visual acuity 12 weeks following surgery.ResultsAt 12 weeks, the mean (SD) visual
acuity was 46.7 (25) ETDRS letters in the control group and 52.6 (21) letters in
the ranibizumab group. Mean visual acuity improved by 14 (31) letters in the
control group and by 24 (27) letters in the ranibizumab group. We found no
difference in the progression of tractional retinal detachment prior to surgery,
the duration of surgery, or its technical difficulty. Vitreous cavity haemorrhage
persisted at 12 weeks in two of the control group but none of the ranibizumab
group.ConclusionRanibizumab pretreatment may improve the outcome of vitrectomy
surgery for advanced proliferative diabetic retinopathy by reducing the extent of
post-operative vitreous cavity haemorrhage. However, the effect size appears to
be modest; we calculate that a definitive study to establish a minimally
important difference of 5.9 letters at a significance level of P<0.05 would
require 348 subjects in each arm.
PMID- 28498376
TI - Two isomorphous Co(ii) coordination polymers based on new alpha,alpha
disubstituted derivatives of zoledronic acid: synthesis, structures and
properties.
AB - Two novel alpha,alpha-disubstituted derivatives of zoledronic acid, namely 1
hydroxy-2-(1H-imidazol-1-yl)-2-methylpropylidene-1,1-diphosphonic acid (H4L1) and
1-hydroxy-2-[1-(1H-imidazol-1-yl)cyclopropyl]ethylidene-1,1-diphosphonic acid
(H4L2) were synthesized and structurally characterized by single-crystal X-ray
diffraction. The reaction of cobalt acetate with H4L1 and H4L2 carried out under
hydrothermal conditions afforded two isomorphous Co3(HL1)2(H2O)6.6H2O (1a) and
Co3(HL2)2(H2O)6.6H2O (2a) complexes. Both compounds are characterized by means of
X-ray crystallography, IR and NIR-Vis-UV spectroscopic methods. Furthermore,
their magnetic properties and thermal stabilities are reported. The crystals of
1a and 2a feature infinite 1D polymeric chains built from alternately arranged
dinuclear [Co2(HL1/HL2)(H2O)2]2 units and {Co1O6} octahedra running along the
[1[combining macron]10] crystallographic direction. In both compounds,
crystallographically distinct Co1 and Co2 atoms are six-coordinated. As is
reflected in T values (T - index of tetragonality), the coordination environment
of Co1 generates a slightly elongated octahedron (T = 0.94), whereas a slightly
compressed octahedron (T = 1.06 for 1a and 1.05 for 2a) is formed around Co2. An
assumption that the d-d type absorption is mainly attributed to the inversion
related Co2 centers, whose population is two times higher than that of Co1,
afforded a good correlation between calculated transition energies and
experimental NIR-Vis-UV spectra. The magnetic susceptibility measurements
analyzed in terms of a spin-3/2 Heisenberg trimer chain revealed that Co1Co2
interactions within the trimer are antiferromagnetic whereas Co2Co2 intertrimer
interactions are ferromagnetic.
PMID- 28498375
TI - Neuro-ophthalmologic manifestations of cholangiocarcinoma: a case series.
AB - PurposeTo describe the neuro-ophthalmologic findings of
cholangiocarcinoma.MethodsWe report a retrospective chart review of
cholangiocarcinoma patients presenting at two tertiary care centers in the Texas
Medical Center.ResultsFive patients with neuro-ophthalmologic symptoms related to
cholangiocarcinoma were identified. One patient presented with diplopia due to
metastasis to the left medial rectus muscle, two patients had metastasis to the
occipital lobe resulting in homonymous hemianopsia, one patient had involvement
of the clivus resulting in sixth nerve palsy, and one presented with a
hypercoagulable state-related stroke causing a homonymous hemianopsia and visual
hallucinations.ConclusionsNeuro-ophthalmic manifestations of cholangiocarcinoma
depend upon both mechanism and localization. We report five cases of
cholangiocarcinoma with neuro-ophthalmologic findings. To our knowledge, this is
the largest such series reported in the English language ophthalmic literature.
PMID- 28498377
TI - Broadband ultrafast photovoltaic detectors based on large-scale topological
insulator Sb2Te3/STO heterostructures.
AB - Topological insulators (TIs) are new states of quantum matter in which the spin
momentum-locked surface states reside in the bulk insulating gap and have
triggered extensive investigations on fundamental properties and potential
applications. Herein, we report scalable, broadband photovoltaic detectors based
on the topological insulator Sb2Te3/strontium titanate (STO) heterostructure.
Large-scale (2 mm * 5 mm), high crystalline quality p-type Sb2Te3 films were
fabricated on an n-type STO substrate by the molecular beam epitaxy (MBE) method.
The Sb2Te3/STO heterostructures exhibited pronounced photovoltaic behavior in a
wide range of temperatures as a result of a strong built-in field at the hetero
interface. Superior performances of broadband (from visible to infrared, 405 nm
1550 nm) and ultrafast (rise time ~30 MUs, fall time ~95 MUs) photoresponses were
achieved under ambient conditions. The prominent repeatability and stability
indicated that our photodetectors can operate effectively in harsh circumstances.
These results show that stacking the topological insulator thin films on a
strongly correlated oxide substrate using the MBE approach holds great promise
for high performance optoelectronic applications.
PMID- 28498378
TI - Reconfigurable optical manipulation by phase change material waveguides.
AB - Optical manipulation by dielectric waveguides enables the transportation of
particles and biomolecules beyond diffraction limits. However, traditional
dielectric waveguides could only transport objects in the forward direction which
does not fulfill the requirements of the next generation lab-on-chip system where
the integrated manipulation system should be much more flexible and
multifunctional. In this work, bidirectional transportation of objects on the
nanoscale is demonstrated on a rectangular waveguide made of the phase change
material Ge2Sb2Te5 (GST) by numerical simulations. Either continuous pushing
forces or pulling forces are generated on the trapped particles when the GST is
in the amorphous or crystalline phase. With the technique of a femtosecond laser
induced phase transition on the GST, we further proposed a reconfigurable optical
trap array on the same waveguide. This work demonstrates GST waveguide's
potential of achieving multifunctional manipulation of multiple objects on the
nanoscale with plausible optical setups.
PMID- 28498379
TI - Non-pericyclic cycloaddition of gem-difluorosubstituted azomethine ylides to the
C[double bond, length as m-dash]O bond: computational study and synthesis of
fluorinated oxazole derivatives.
AB - The cycloaddition of arenecarbaldehydes and alpha,alpha,alpha
trifluoroacetophenones with gem-difluoro-substituted azomethine ylides, generated
from N-benzhydrylideneamines and difluorocarbene, occurs regioselectively to
give, after hydrolysis, oxazolidin-4-ones. The primary cycloadducts of
trifluoroacetophenones, 4,4-difluoro-5-trifluoromethyloxazolidine derivatives,
are sufficiently stable to be isolated in reasonable to excellent yields. The
results of correlation analysis and DFT calculations reveal a non-pericyclic step
wise mechanism of the reaction. The replacement of the two geminal hydrogen atoms
in the azomethine ylide intermediate for fluorine atoms results in a dramatic
change in the reaction mechanism from pericyclic to step-wise, proceeding via a
zwitterion-like transition state in which no C-O bonding is observed.
PMID- 28498380
TI - Helix-sense-selective co-precipitation for preparing optically active helical
polymer nanoparticles/graphene oxide hybrid nanocomposites.
AB - Constructing optically active helical polymer based nanomaterials without using
expensive and limited chirally helical polymers has become an extremely
attractive research topic in both chemical and materials science. In this study,
we prepared a series of optically active helical polymer nanoparticles/graphene
oxide (OAHPNs/GO) hybrid nanocomposites through an unprecedented strategy-the co
precipitation of optically inactive helical polymers and chirally modified GO.
This approach is named helix-sense-selective co-precipitation (HSSCP), in which
the chirally modified GO acted as a chiral source for inducing and further
stabilizing the predominantly one-handed helicity in the optically inactive
helical polymers. SEM and TEM images show quite similar morphologies of all the
obtained OAHPNs/GO nanocomposites; specifically, the chirally modified GO sheets
were uniformly decorated with spherical polymer nanoparticles. Circular dichroism
(CD) and UV-vis absorption spectra confirmed the preferentially induced helicity
in the helical polymers and the optical activity of the nanocomposites. The
established HSSCP strategy is thus proven to be widely applicable and is expected
to produce numerous functional OAHPNs/GO nanocomposites and even the analogues.
PMID- 28498381
TI - A theoretical study of the light-induced cross-linking reaction of 5-fluoro-4
thiouridine with thymine.
AB - In contrast to photophysics of thio-substituted nucleobases, their photoinduced
cross-linking reactions with canonical nucleobases remain scarcely investigated
computationally. In this work, we have adopted combined CASPT2/PCM//CASSCF and
B3LYP-D3/PCM electronic structure methods to study this kind of photochemical
reaction of 5-fluoro-4-thiouridine (truncated 5-fluoro-1-methyl-4-thiouracil used
in calculations) and 1-methylthymine (referred to as thymine for clarity
hereinafter). On the basis of CASPT2/PCM computed results, we have proposed two
efficient excited-state relaxation pathways to populate the lowest T1 state of
the complex of 5-fluoro-1-methyl-4-thiouracil and thymine from its initially
populated S2(1pipi*) state. In the first one, the S2 system first hops to the S1
state via an S2/S1 conical intersection, followed by a direct S1 -> T1
intersystem crossing process enhanced by large S1/T1 spin-orbit coupling. In the
second path, the resultant S1 system first jumps to the T2 state, from which an
efficient T2 -> T1 internal conversion occurs. The T1 cross-linking reaction is
overall divided into two phases. The first phase is a stepwise and nonadiabatic
photocyclization reaction, which starts from the T1 complex and ends up with an
S0 thietane intermediate. The second phase is a thermal reaction. The system
first rearranges its four- and six-membered rings to form three new rings; then,
an S0 fluorine atom transfer occurs, followed by the formation of photoproducts.
Finally, the present work paves the way for studying light-induced cross-linking
reactions of thionucleobases with canonical bases in DNA and RNA.
PMID- 28498382
TI - Rapid assembly of the doubly-branched pentasaccharide domain of the
immunoadjuvant jujuboside A via convergent B(C6F5)3-catalyzed glycosylation of
sterically-hindered precursors.
AB - A convergent synthesis of the complex, doubly-branched pentasaccharide domain of
the natural-product immunoadjuvant jujuboside A is described. The key step is a
sterically-hindered glycosylation reaction between a branched trisaccharide
trichloroacetimidate glycosyl donor and a disaccharide glycosyl acceptor.
Conventional Lewis acids (TMSOTf, BF3.Et2O) were ineffective in this
glycosylation, but B(C6F5)3 catalyzed the reaction successfully. Inherent
complete diastereoselectivity for the undesired alpha-anomer was overcome by
rational optimization with a nitrile solvent system (1 : 5 t-BuCN/CF3Ph) to
provide flexible, effective access to the beta-linked pentasaccharide.
PMID- 28498384
TI - Highly efficient oxygen evolution from CoS2/CNT nanocomposites via a one-step
electrochemical deposition and dissolution method.
AB - The oxygen evolution reaction (OER) has been viewed as a critical step in
electrochemical energy conversion and storage devices. However, searching for
cheap and efficient OER electrocatalysts still remains an urgent task. Herein, we
develop a new strategy involving a one-step electrochemical deposition and
dissolution method to fabricate hydrophilic porous CoS2/carbon nanotube (CNT)
composites (CNT-CoS2). X-ray photoelectron spectroscopy and near-edge X-ray
absorption fine structure spectroscopy measurements confirm the formation of
hydrophilic groups on the surface of the porous CoS2 during electrochemical
oxidation. Our design holds several advantages. The electricity conductivity of
CoS2 is increased by introducing CNTs as a conductive substrate. The porous
nanostructures of CoS2 increase its surface area, and provide paths to promote
charge and reactant transfer. The active edge sites modified with hydrophilic
groups can increase the content of electrolyte-electrode contact points,
increasing the intrinsic catalytic performance of CoS2. These factors allow CNT
CoS2 to achieve a low onset potential of 1.33 V vs. RHE, a stable current density
(j) of 10 mA cm-2 at an overpotential of 290 mV, and excellent stability under
alkaline conditions compared to that of IrO2. The comprehensive performance of
the CNT-CoS2 electrocatalyst is comparable to or better than that of any reported
noble metal-free OER catalyst, even RuO2 and IrO2. This facile synthesis strategy
involving synchronous electrochemical deposition and dissolution should be easily
adapted for large-scale water electrolysis.
PMID- 28498385
TI - Polymer brushes based on PLLA-b-PEO colloids for the preparation of protein
resistant PLA surfaces.
AB - In this study we investigate the formation of protein-resistant polymer surfaces,
such as aliphatic polyesters, through the deposition of self-assemblies of
amphiphilic poly(l-lactide)-b-poly(ethylene oxide), PLLA-b-PEO, copolymers as
stable nanoparticles with a kinetically frozen PLLA core on model PLLA surfaces.
The length of the PEO chains in the corona was tuned to achieve polymer brushes
capable of preventing protein adsorption on PLA-based biomaterials. The
spectroscopic ellipsometry, IR and XPS analysis, contact angle goniometry, and
AFM proved that the PEO chains adopted a brush structure and were preferably
exposed on the surface. The low-fouling properties of the physisorbed PLLA-b-PEO
layers approached the ones of reactive grafting methods, as shown by surface
plasmon resonance spectroscopy. The anti-fouling properties of the prepared PEO
brushes provided sufficient interface to prevent cell adhesion as proved in
vitro. Thus, the developed surface coating with PLLA-b-PEO colloids can provide
an anti-fouling background for the creation of nanopatterned biofunctionalized
surfaces in biomedical applications.
PMID- 28498387
TI - The Need for Linguistically and Culturally Adapted Standard Questionnaires to
Assess Itch: A Preliminary Study.
PMID- 28498386
TI - Atorvastatin inhibits cholesterol-induced caspase-3 cleavage through down
regulation of p38 and up-regulation of Bcl-2 in the rat carotid artery.
AB - AIM: Atherosclerotic lesions in the carotid arteries lead to a broad range of
cerebrovascular disorders such as vascular dementia and ischaemic stroke. Recent
studies have verified the beneficial role of atorvastatin (AV) in
atherosclerosis. Despite a large body of studies, the mechanisms underlying this
effect have not been completely explained. In this study, several experiments
were performed on atherosclerotic rat models to investigate the anti-inflammatory
and anti-apoptotic effect of AV in the carotid artery. METHODS: In this
experimental study, 40 male Wistar rats (250 +/- 25 g) were randomly divided into
four groups: rats on a normal diet (ND; n = 10); a high-cholesterol diet (HD; n =
10); a high-cholesterol diet plus AV (HD + AV; n = 10) ; and the AV control group
(AV; n = 10). Cleavage of caspase-3 protein, expression of B-cell lymphoma 2 (Bcl
2) as well as phosphorylation of p38 mitogen-activated protein kinase (MAPK) were
determined by immunoblotting assay in the carotid artery homogenate. Plasma
atherogenic indices, including total cholesterol (TC), high-density lipoprotein
cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured
by colorimetric assay at the end of the experiment. Plasma levels of oxidised LDL
(oxLDL) were measured by sandwich enzyme-linked immunosorbent assay (ELISA).
RESULTS: After eight weeks of feeding with a high-cholesterol diet, an elevated
level of oxLDL was observed in the plasma in the HD group compared with the ND
group [214.42 +/- 17.46 vs 69.13 +/- 9.92 mg/dl (5.55 +/- 0.45 vs 1.78 +/- 0.26
mmol/l); p < 0.01]. AV administration significantly reduced oxLDL levels in the
HD + AV compared to the HD group [126.52 +/- 9.46 vs 214.42 +/- 17.46 mg/dl (3.28
+/- 0.25 vs 5.55 +/- 0.45 mmol/l); p < 0.01]. Results also showed that compared
with the HC group, the HC + AV group had lower levels of p38 phosphorylation (p <
0.05) and higher levels of Bcl-2 expression (p < 0.05). Lower levels of cleaved
caspase-3 were observed in the HC + AV group in comparison with the HC group (p <
0.05). CONCLUSIONS: The resultant data suggest that the anti-apoptotic effect of
AV could be partially mediated by the pro-inflammatory protein p38 MAPK and the
anti-apoptotic protein Bcl-2 in the rat carotid artery. Atorvastatin can
therefore be considered a target drug in the prevention or development of
atherosclerotic events.
PMID- 28498388
TI - Chronic Pain in Patients with Skin Disorders.
PMID- 28498389
TI - Next-generation Sequencing Identified a Novel EDA Mutation in a Chinese Pedigree
of Hypohidrotic Ectodermal Dysplasia with Hyperplasia of the Sebaceous Glands.
PMID- 28498390
TI - Substrate stiffness affects epithelial-mesenchymal transition of cervical cancer
cells through miR-106b and its target protein DAB2.
AB - The effects of different substrate stiffness were investigated on epithelial
mesenchymal transition (EMT) of cervical cancer cell lines and the role of miR
106b and its target protein DAB2 therein. Cervical cancer cell lines HeLa and
SiHa were cultured on artificial substrates with different stiffness prepared
using different ratios of acrylamide and bis-acrylamide. Changes of microRNA
profiles were detected using microRNA chip analysis, and the expression levels of
EMT-related markers E-cadherin and vimentin were detected using western blotting
and real-time PCR. In addition, the effects of miR-106b overexpression as well as
miR-106b and DAB2 knockdown on expression of E-cadherin and vimentin were also
examined using western blotting and real-time PCR. The results showed that i)
cervical cancer cell lines SiHa and HeLa cultured on substrate with stiffness of
20 kPa had the strongest EMT ability, showed the highest levels of vimentin and
lowest levels of E-cadherin, compared with cells cultured on substrate with
stiffness of 1 kPa; ii) miR-106b knockdown reversed the effects of substrate
stiffness on EMT of cervical cancer cells, while miR-106 overexpression and DAB2
knockdown induced EMT of cervical cancer cells cultured on substrate with
stiffness of 20 kPa. Overall, the results indicated that substrate stiffness
could regulate EMT of cervical cancer cell lines HeLa and SiHa at least partially
through miR-106b and its downstream target DAB2.
PMID- 28498391
TI - Hypospadias in a male infant with an unusual mosaic 45,X/46,X,psu
idic(Y)(p11.32)/46,XY and haploinsufficiency of SHOX: A case report.
AB - A male newborn presented with hypospadias and differential testicular volumes.
Short femur length was detected four times during pregnancy, at 23, 31, 32 and 33
weeks, by ultrasonographic examination. Chromosome analysis was performed on
peripheral lymphocytes obtained from the infant and his parents. Fluorescent in
situ hybridization (FISH), using sex determining region Y (SRY)/DXZ1 and DYZ3
probes, was performed to verify the deletion of the SRY gene (located on Yp11.3
region) and the activation of Y chromosomal centromeres. Single nucleotide
polymorphism (SNP)-array comparative genomic hybridization (CGH) was used to
detect copy number variations in the infant. The results revealed a ~2.2 Mb
mircodeletion on Yp11.32 containing the short stature homeobox (SHOX) gene.
According to the above examinations, the abnormal Y chromosome of the patient was
identified as a dicentric derivate of the Y chromosome with pseudoinactivation of
one of the two centromeres. The karyotype is therefore:
45,X[20]/46,X,idic(Y)(p11.3).ish psu idic(Y)(p11.3) (SRY++, DYZ3++). array
Yp11.32 (118,551-2,393,500)x0[26]/46,X,ishY(SRY+, DYZ3+)[4]. The combination of
cytogenetic, FISH and SNP-array CGH technologies was beneficial for diagnosing
the karyotype accurately, predicting the prognosis, and preparing an effective
treatment plan for the patient.
PMID- 28498392
TI - The flightless I protein interacts with RNA-binding proteins and is involved in
the genome-wide mRNA post-transcriptional regulation in lung carcinoma cells.
AB - The flightless I protein (FLII) belongs to the gelsolin family. Its function has
been associated with actin remodeling, embryonic development, wound repair, and
more recently with cancer. The structure of FLII is characterized by the N
terminal leucine-rich repeats (LRR) and C-terminal gesolin related repeated units
that are both protein-protein inter-action domains, suggesting that FLII may
exert its function by interaction with other proteins. Therefore, systematic
study of protein interactions of FLII in cells is important for the understanding
of FLII functions. In this study, we found that FLII was downregulated in lung
carcinoma cell lines H1299 and A549 as compared with normal HBE (human bronchial
epithelial) cell line. The investigation of FLII interactome in H1299 cells
revealed that 74 of the total 132 putative FLII interactors are involved in RNA
post-transcriptional modification and trafficking. Furthermore, by using high
throughput transcriptome and translatome sequencing combined with cell
fractionation, we showed that the overexpression or knockdown of FLII impacts on
the overall nuclear export, and translation of mRNAs. IPA analysis revealed that
the majority of these target mRNAs encode the proteins whose functions are
reminiscent of those previously reported for FLII, suggesting that the post
transcriptional regulation of mRNA might be a major mechanism of action for FLII.
PMID- 28498393
TI - Upregulation of circadian gene 'hClock' contribution to metastasis of colorectal
cancer.
AB - Recent studies have shown that disruption of the circadian rhythm was one of the
endogenous factors contributing to tumorigenesis of various human malignancies,
including colorectal cancer (CRC). However, the roles of circadian genes in the
development of CRC are still unexplored. In this study, we investigated the
expression pattern and the underlying mechanism of human Clock gene (hClock) in
CRC progression. Multiple methods such as qRT-PCR, immunohistochemistry, and
western blotting were performed to evaluate the expression pattern of the gene
hClock, as well as to observe the changes of angiogenesis-related proteins and
EMT-related proteins. Transwell cell migration assays and an animal tumor
metastasis model were used to examine the impact of hClock on the metastatic
ability of CRC cells in vitro and in vivo. Our results showed that the expression
level of hClock significantly increased in human CRC tissues, which strongly
associated with late TNM stage and positive lymph node metastasis. Moreover, a
higher level of hClock expression was found in CRC cell lines with a higher
metastatic potential. Furthermore, ectopic expression of hClock promoted the
migration of SW480 CRC cells, while knockdown of hClock inhibited the tumor
metastasis of SW620 CRC cells, and targeting hClock by shRNA effectively
suppressed the metastatic ability of SW620 CRC cells in nude mice. Finally, we
found that overexpression of hClock enhanced the expression of angiogenesis
related genes such as HIF-1alpha, ARNT and VEGF, and promoted epithelial
mesenchymal (-like) transition (EMT) in CRC cells, both of which are considered
to be critical for tumor progression. These findings suggest that upregulation of
the circadian gene hClock plays an important role in metastasis of colorectal
cancer.
PMID- 28498394
TI - miR-34b attenuates trauma-induced anxiety-like behavior by targeting CRHR1.
AB - Exposure to trauma is a potential contributor to anxiety; however, the molecular
mechanisms responsible for trauma-induced anxiety require further clarification.
In this study, in an aim to explore these mechanisms, we observed the changes in
the hypothalamic pituitary adrenal (HPA) axis using a radioimmunoassay and the
changes in anxiety-like behavior using the open field test and elevated plus maze
test in a rat model following intervention with NBI-27914, a specific
corticotropin-releasing hormone receptor 1 (CRHR1) antagonist. CRHR1 was found to
be involved in trauma-induced anxiety. We then applied bioinformatic analysis to
screen microRNAs (miRNAs or miRs) that target CRHR1, and miR-34b was determined
to negatively regulate CRHR1 mRNA in primary hypothalamic neurons. The
overexpression of miR-34b in the paraventricular nucleus (PVN) by a miRNA agomir
using a drug delivery system decreased the hyperactivity of the HPA axis and
anxiety-like behavior. Overall, the involvement of the HPA axis in trauma-induced
anxiety was demonstrated, and trauma-induced anxiety was attenuated by decreasing
the hyperactivity of the HPA axis via miR-34b by targeting CRHR1.
PMID- 28498395
TI - MicroRNA-1299 is a negative regulator of STAT3 in colon cancer.
AB - Signal transducers and activators of transcription (STAT) is a family of
transcription factors which regulate cell proliferation, differentiation,
apoptosis, metastasis, immune and inflammatory responses, and angiogenesis. STAT3
is a latent cytoplasmic transcription factor that belongs to STATs. STAT3 has
been reported be regulates genes involved with cellular growth, proliferation and
metastasis. Worldwide, colon cancer is one of the leading causes of cancer
related deaths. Cumulative evidence has established that STAT3 is essential for
colon cancer progression to advanced malignancy. In our study, we showed that
microRNA-1299 (miR-1299) was closely related to the TNM stage of colon cancer,
and that the expression of miR-1299 was negatively correlated with the expression
of STAT3 in colon cancer which means that miR-1299 can be a negative regulator of
STAT3 in colon cancer. A total of 60 cases of different grades of colon samples
were used to detect the expression of miR-1299. Results showed that miR-1299 was
significantly lower in high-grade colons both in mRNA and protein levels.
Furthermore, Overall survival (OS) in patients with low miR-1299 is shorter than
25.6 months, as compared with an OS of 28.4 months in patients with high level of
miR-1299. We also confirmed that the overexpression of miR-1299 can not only
downregulate the STAT3 pathway, but also inhibited colon cancer cell growth. Our
findings could provide new insights into the molecular therapeutic of colon
cancer.
PMID- 28498396
TI - Diverse expression patterns and tumorigenic role of neurotensin signaling
components in colorectal cancer cells.
AB - Colorectal cancer (CRC), which is one of the most common malignancies worldwide,
results from an accumulation of genetic and epigenetic modifications including
DNA methylation. Neurotensin (NTS), a hormone localized to the gut and central
nervous system, mediates its physiological and pathological effects, including
growth stimulation for a variety of cancers, through three distinct NTS receptors
(NTSRs). Most NTS functions are mediated through the high-affinity receptor
NTSR1, and expression of NTSR1 is increased in many cancers including CRC. In
this study, we investigated the expression profiles and cellular functions of the
NTSRs, especially NTSR1, in CRC cells. We showed that expression levels for NTS
and NTSR1 varied, that NTSR2 expression was not detectable and that NTSR3 was
consistently expressed in all CRC cell lines examined. Treatment with the
demethylating agent, 5-aza-2'-deoxycytidine, augmented levels of NTSR1/2 in Caco2
and DLD1 cells, which have little or no transcripts for NTSR1/2 suggesting that
DNA methylation suppresses NTSR1/2 expression. In addition, we demonstrated that
knockdown of NTSR1 decreased cell growth and migration in HCT116 and HT29 cells.
Finally, we showed that treatment with SR48692, an antagonist of NTSR1, also
inhibited cell proliferation and migration in the CRC cells. Our findings
identify promoter methylation as an important process regulating the differential
expression or silencing of NTSR1/2 in CRC cells. Moreover, inhibition of NTSR1
repressed tumorigenic effects in CRC cells, suggesting that NTSR1 may be used as
a therapeutic target for CRC.
PMID- 28498397
TI - Dihydroartemisinin inhibits the viability of cervical cancer cells by
upregulating caveolin 1 and mitochondrial carrier homolog 2: Involvement of p53
activation and NAD(P)H:quinone oxidoreductase 1 downregulation.
AB - Dihydroartemisinin (DHA) has been shown to inhibit the viability of various
cancer cells. Previous studies have revealed that the mechanisms involved in the
inhibitory effects of DHA are based on theactivation of p53 and the mitochondrial
related cell death pathway. However, the exact association between upstream
signaling and the activation of cell death pathway remains unclear. In this
study, we found that DHA treatment induced the upregulation of caveolin 1 (Cav1)
and mitochondrial carrier homolog 2 (MTCH2) in HeLa cells, and this was
associated with the DHA-induced inhibition of cell viability and DHA-induced
apoptosis. Additionally, the overexpression of Cav1 and MTCH2 in HeLa cells
enhanced the inhibitory effects of DHA on cell viability. Moreover, we also found
that the upregulation of Cav1 contributed to the DHA-mediated p53 activation and
the downregulation of the redox enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1),
which have been reported to contribute to the activation of the cell death
pathway. Of note, we also found that DHA induced the nuclear translocation and
accumulation of both Cav1 and p53, indicating a novel potential mechanism, namely
the regulation of p53 activation by Cav1. On the whole, our study identified Cav1
and MTCH2 as the molecular targets of DHA and revealed a new link between the
upstream Cav1/MTCH2 upregulation and the downstream activation of the cell death
pathway involved in the DHA-mediated inhibition of cell viability.
PMID- 28498398
TI - PER2 is downregulated by the LPS-induced inflammatory response in synoviocytes in
rheumatoid arthritis and is implicated in disease susceptibility.
AB - The clinical symptoms of rheumatoid arthritis (RA) present with circadian
variation, with joint stiffness and pain more prominent in the early morning. The
mammalian clock genes, which include circadian locomotor output cycles kaput,
brain and muscle Arnt-like protein 1, period and cryptochrome, regulate circadian
rhythms. In order to identify the association between genetic polymorphisms in
the circadian clock gene period 2 (PER2) and RA, the present study genotyped
three PER2 single nucleotide polymorphisms (SNPs), rs934945, rs6754875, and
rs2304674, using genetic information from 256 RA patients and 499 control
subjects. Primary cultured rheumatoid synovial cells were stimulated with 10 uM
lipopolysaccharide (LPS). Total protein was then extracted from the synovial
cells following 12 and 24 h, and PER2 protein expression was assayed by
immunoblotting. The rs2304674 SNP demonstrated a significant association with
susceptibility to RA following Bonferroni correction. However, statistical
analysis indicated that the SNPs were not associated with any clinical features
of patients with RA. Immunoblotting analysis demonstrated that PER2 protein
expression was decreased by LPS-induced inflammation in RA synovial cells;
however, this was not observed in normal synovial cells. The results suggest that
the PER2 gene may be a risk factor for RA, and expression of the PER2 protein may
be affected by inflammation. Therefore, PER2 may contribute to the pathogenesis
of RA.
PMID- 28498399
TI - Dual inhibition of IGF1R and ER enhances response to trastuzumab in HER2 positive
breast cancer cells.
AB - Although HER2 targeted therapies have improved prognosis for HER2 positive breast
cancer, HER2 positive cancers which co-express ER have poorer response rates to
standard HER2 targeted therapies, combined with chemotherapy, than HER2
positive/ER negative breast cancer. Administration of hormone therapy
concurrently with chemotherapy and HER2 targeted therapy is generally not
recommended. Using publically available gene expression datasets we found that
high expression of IGF1R is associated with shorter disease-free survival in
patients whose tumors are ER positive and HER2 positive. IGF1R is frequently
expressed in HER2 positive breast cancer and there is significant evidence for
crosstalk between IGF1R and both HER2 and ER. Therefore, we evaluated the
therapeutic potential of targeting ER and IGF1R in cell line models of
HER2/ER/IGF1R positive breast cancer, using tamoxifen and two IGF1R targeted
tyrosine kinase inhibitors (NVP-AEW541 and BMS-536924). Dual inhibition of ER and
IGF1R enhanced growth inhibition in the four HER2 positive cell lines tested and
caused an increase in cell cycle arrest in G1 in BT474 cells. In addition,
combined treatment with trastuzumab, tamoxifen and either of the IGF1R TKIs
enhanced response compared to dual targeting strategies in three of the four HER2
positive breast cancer cell lines tested. Furthermore, in a cell line model of
trastuzumab-resistant HER2 positive breast cancer (BT474/Tr), tamoxifen combined
with an IGF1R TKI produced a similar enhanced response as observed in the
parental BT474 cells suggesting that this combination may overcome acquired
trastuzumab resistance in this model. Combining ER and IGF1R targeting with HER2
targeted therapies may be an alternative to HER2 targeted therapy and
chemotherapy for patients with HER2/ER/IGF1R positive breast cancer.
PMID- 28498400
TI - TRIM28 knockdown increases sensitivity to etoposide by upregulating E2F1 in non
small cell lung cancer.
AB - Tripartite motif containing 28 (TRIM28) is a universal corepressor for Kruppel
associated box zinc finger proteins. In our previous study, it was shown that
expression of TRIM28 is upregulated in non-small cell lung cancer (NSCLC) cell
lines and tissues. Here, we demonstrated that the stable silencing of TRIM28
expression by a specific siRNA lentivirus vector increased the sensitivity of
NSCLC cells to chemotherapeutic agent etoposide. Combination of TRIM28 siRNA and
etoposide significantly inhibited the growth and proliferation of lung
adenocarcinoma PAa cells and exerted obvious antitumor effects in nude mice.
Using FCM and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end
labeling (TUNEL) assay, we found that TRIM28 siRNA in combination with etoposide
increased apoptosis in vitro and in vivo which was induced by E2F1 activity,
since the expression of E2F1 and its target genes was significantly increased in
the cotreatment group. Cell proliferation and apoptosis were almost completely
abolished in the PAa cells cotreated with TRIM28 siRNA and etoposide following
knockdown of E2F1. The results of our study demonstrated that the combination of
TRIM28 siRNA and etoposide may be effective against NSCLC and has the potential
of being a new therapeutic tool for future treatment.
PMID- 28498401
TI - Luteolin-induced apoptosis through activation of endoplasmic reticulum stress
sensors in pheochromocytoma cells.
AB - Luteolin [2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-chromenone] is an active
flavonoid compound from Lonicera japonica (Caprifoliaceae). Luteolin inhibits
tumor cell proliferation, inflammatory and oxidative stress better, when compared
with other flavonoids. In the present study, it was demonstrated that luteolin
induces typical apoptosis in PC12 cells (derived from a pheochromocytoma of the
rat adrenal medulla) accompanied by DNA fragmentation and formation of apoptotic
bodies. In addition, luteolin regulates expression of the endoplasmic reticulum
(ER) chaperone binding immunoglobulin protein, activating ER stress sensors
(eukaryotic initiation factor 2alpha phosphorylation and X-box binding protein 1
mRNA splicing) and induced autophagy. The results indicated that luteolin induces
the upregulation of the unfolded protein response pathway through the ER stress
sensors, which helps as an influential regulator for the apoptosis pathway in
PC12 cells. The results suggested that the understanding of the molecular
mechanisms underlying luteolin-induced apoptosis may be useful in cancer
therapeutics, chemoprevention and neurodegenerative diseases, such as Parkinson's
disease and Alzheimer's disease.
PMID- 28498402
TI - Effects of RUNX3 mediated Notch signaling pathway on biological characteristics
of colorectal cancer cells.
AB - This study investigated the effects of runt-related transcription factor 3
(RUNX3) mediated Notch pathway on the biological behavior of colorectal cancer
(CRC) SW260 cells. CRC tissues and para-carcinoma tissues were collected from 182
CRC patients who had undergone surgical treatment between January 2008 and
December 2010. Immunohistochemical staining with streptavidin-peroxidase (SP) was
used to detect RUNX3, Notch1 and Jagged 1 expression levels. CRC SW260 cells were
divided into the following groups: Control group, si-NC group, si-RUNX3 group,
DAPT group, si-RUNX3+DAPT group, and si-NC+DAPT group. Expression levels of
RUNX3, and Notch signaling related genes were measured by real-time fluorescence
quantitative polymerase chain reaction (RT-qPCR) and western blotting in vitro.
Besides, MTT, soft agar colony formation, Annexin V-FITC/PI double staining and
Transwell were performed to analyze the effects of RUNX3 on cell growth and
metastasis. Lower positive expression rate of RUNX3 and higher positive
expression rate of Notch1 and Jagged 1 were observed in CRC tissues than those in
normal adjacent tissues with a negative correlation, and the expression levels
were associated with the differentiation degree, TNM staging, lymph node
metastasis and tumor invasion depth (all P<0.05). RUNX3 expression was reduced in
si-RUNX3 and si-RUNX3+DAPT group but the expression levels of Notch signaling
related genes were markedly increased in si-RUNX3 group or decreased in DAPT and
si-NC+DAPT group, as compared with those in the control group (all P<0.05). In
addition, the proliferation, colony formation, migration and invasion abilities
of SW260 cells were enhanced in si-RUNX3 group but were restricted in DAPT and si
NC+DAPT group, which was contrary to cell apoptosis (all P<0.05). RUNX3
contributes to attenuate the proliferation and metastasis of CRC cells, and
promotes cell apoptosis through inhibition of Notch signaling pathway.
PMID- 28498403
TI - Mus musculus-microRNA-449a ameliorates neuropathic pain by decreasing the level
of KCNMA1 and TRPA1, and increasing the level of TPTE.
AB - Neuropathic pain is a nerve disorder characterized by the dysregulation of ion
channels in dorsal root ganglion (DRG) neurons. MicroRNAs (miRs) may be
associated with the molecular mechanisms underlying the altered levels of ion
channels; however, the molecular mechanisms remain widely unknown. To investigate
these mechanisms, the present study conducted a genomic analysis of miR between a
unilateral spared nerve injury (SNI) model and sham control. Differentially
expressed miRs between the SNI and sham groups were selected for transfection of
DRG cells, a polymerase chain reaction (PCR) array analysis was subsequently
performed. A total of three significantly differently expressed genes were
selected from the results of the PCR array and further analyzed by reverse
transcription-quantitative PCR. Genomic analysis revealed that Mus musculus miR
449a (mmu-miR-449a) was reduced in the SNI groups compared with the sham
controls. The PCR array indicated that mmu-miR-449a-transfection reduced the mRNA
expression levels of transient receptor potential cation channel subfamily A
member 1 (TRPA1), and calcium-activated potassium channel subunit alpha-1
(KCNMA1) and increased the level of transmembrane phosphatase with tension
homology (TPTE) in the DRG cells (P<0.05). qRT-PCR analysis further indicated
that mmu-miR-449a transfection caused similar alterations in the mRNA expression
levels of TRPA1, KCNMA1 and TPTE in DRG cells, respectively (P<0.05). Therefore,
mmu-miR-449a may ameliorate neuropathic pain by decreasing the activity of the
channel proteins TRPA1 and KCNMA1 and increasing the levels of TPTE. mmu-miR-449a
may be a potential therapeutic molecule for the alleviation of neuropathic pain.
PMID- 28498404
TI - Methylation modification in gastric cancer and approaches to targeted epigenetic
therapy (Review).
AB - Gastric cancer (GC) is one of the most common cancers and the second leading
cause of cancer-related mortality. Increasing discoveries have highlighted
aberrant epigetic modifications actively contribute to the pathogenesis of this
fatal disease. Among these epigenetic events, dysregulated methylation is
particularly associated with GC progression. Importantly, these aberrant
methylation modifications caused by the misregulation of methyltranferases are
frequently reversible, which provides opportunities for targeted treatment using
specific molecular inhibitors. In the present review, we provide an overview of
the current literature on the changes of DNA and histone methylations that alter
gene expressions in GC and describe the emerging targeted epigenetic therapy in
GC.
PMID- 28498405
TI - Application of metabolomics: Focus on the quantification of organic acids in
healthy adults.
AB - Metabolomics, a 'budding' discipline, may accurately reflect a specific phenotype
which is sensitive to genetic and epigenetic interactions. This rapidly evolving
field in science has been proposed as a tool for the evaluation of the effects of
epigenetic factors, such as nutrition, environment, drug and lifestyle on
phenotype. Urine, being sterile, is easy to obtain and as it contains metabolized
or non-metabolized products, is a favored study material in the field of
metabolomics. Urine organic acids (OAs) reflect the activity of main metabolic
pathways and have been used to assess health status, nutritional status, vitamin
deficiencies and response to xenobiotics. To date, a limited number of studies
have been performed which actually define reference OA values in a healthy
population and as reference range for epigenetic influences, and not as a
reference to congenital metabolic diseases. The aim of the present study was thus
the determination of reference values (RVs) for urine OA in a healthy adult
population. Targeted metabolomics analysis of 22 OAs in the urine of 122 healthy
adults by gas chromatography-mass spectrometry, was conducted. Percentile
distributions of the OA concentrations in urine, as a base for determining the
RVs in the respective population sample, were used. No significant differences
were detected between female and male individuals. These findings can facilitate
the more sensitive determination of OAs in pathological conditions. Therefore,
the findings of this study may contribute or add to the information already
available on urine metabolite databases, and may thus promote the use of targeted
metabolomics for the evaluation of OAs in a clinical setting and for
pathophysiological evaluation. However, further studies with well-defined
patients groups exhibiting specific symptoms or diseases are warranted in order
to discern between normal and pathological values.
PMID- 28498406
TI - Crizotinib, a MET inhibitor, prevents peritoneal dissemination in pancreatic
cancer.
AB - Peritoneal dissemination is a frequent occurrence in pancreatic cancer, which is
associated with a poor prognosis. MET is associated with the progression of
pancreatic cancer; therefore, we evaluated the effect of a MET inhibitor,
crizotinib, on peritoneal dissemination of pancreatic cancer. Crizotinib
inhibited the growth of 8 pancreatic cancer cell lines with the IC50 ranging from
1.4 to 4.3 uM. Invasion of the pancreatic cancer cell line Suit-2, was suppressed
in vitro at a concentration of 1.0 uM, which is sufficient for the inhibition of
MET phosphorylation. This effect on cell invasion was also recapitulated by the
reduction of MET expression in Suit-2 with siRNA. Crizotinib also inhibited RhoA
activation in addition to MET phosphorylation. We further evaluated the effect of
crizotinib on peritoneal dissemination of pancreatic cancer in vivo. Crizotinib
reduced tumor burden and ascites accumulation due to development of peritoneal
dissemination after inoculation of Suit-2. Taken together, crizotinib may be a
potent drug for treating peritoneal dissemination of pancreatic cancer by
inhibiting cancer cell proliferation and invasion, at least in part through the
suppression of HGF/MET signaling and RhoA activation.
PMID- 28498407
TI - Respiratory syncytial virus infection accelerates lung fibrosis through the
unfolded protein response in a bleomycin-induced pulmonary fibrosis animal model.
AB - Emerging evidence has demonstrated that endoplasmic reticulum stress (ER) is
involved in the pathogenesis of idiopathic pulmonary fibrosis, however, the
underlying mechanism remains unclear. Viral infection often triggers a
hyperinflammatory response by an expansion of the ER. The present study was
designed to observe the role of respiratory syncytial virus infection (RSV)
induced ER stress on lung fibrosis. In order to determine the role of ER stress
on the onset and progression of pulmonary fibrosis, mice received an
intratracheal combined injection of RSV and bleomycin on day 0. At day 7, 14 and
21 following combined injection, RSV in the lung tissues was assayed by
immunohistochemistry, cellular classification was assayed by direct microscopic
observation after Wright staining and the secretion of cytokines in the broncho
alveolar lavage fluid (BALF) was assayed by ELISA. The expression of collagen
type I was assayed by immunofluorescence and western blot analysis. The
expression of ER stress related proteins was analyzed by western blot. In
addition, the correlations of ER-stress related proteins with collagen type-1
were examined. RSV administration resulted in increased inflammation, as
demonstrated by increased levels of leukocytes and pro-inflammatory cytokines in
the BALF, and increased collagen type-1 deposition in the lung tissues of
bleomycin-induced pulmonary fibrosis animal model at 7, 14 and 21 days. RSV
promoted the expression of phosphorylated protein kinase R-like endoplasmic
reticulum kinase (p-PERK), 78 kDa glucose-regulated protein (GRP78) and
activating transcription factor 6alpha (ATF6alpha), which accelerated the
severity and process of fibrosis in bleomycin-induced animal models. The present
study provides evidence that RSV infection accelerated the unfolded protein
response and bleomycin-induced lung fibrosis, which may improve our understanding
of the pathogenesis of pulmonary fibrosis.
PMID- 28498408
TI - Induction of IL-17 production from human peripheral blood CD4+ cells by asbestos
exposure.
AB - We have previously reported that chronic, recurrent and low-dose exposure to
asbestos fibers causes a reduction in antitumor immunity. Investigation of
natural killer (NK) cells using an in vitro cell line model and comprising in
vitro activation using freshly isolated NK cells co-cultured with chrysotile
fibers, as well as NK cells derived from asbestos-exposed patients with pleural
plaque (PP) or malignant mesothelioma (MM), revealed decreased expression of NK
cell activating receptors such as NKG2D, 2B4 and NKp46. An in vitro
differentiation and clonal expansion model for CD8+ cytotoxic T lymphocytes
(CTLs) showed reduced cytotoxicity with decreased levels of cytotoxic molecules
such as granzyme B and perforin, as well as suppressed proliferation of CTLs.
Additionally, analysis of T helper cells showed that surface CXCR3, chemokine
receptor, and the productive potential of interferon (IFN)gamma were reduced
following asbestos exposure in an in vitro cell line model and in peripheral CD4+
cells of asbestos-exposed patients. Moreover, experiments revealed that asbestos
exposure enhanced regulatory T cell (Treg) function. This study also focused on
CXCR3 expression and the Th-17 cell fraction. Following activation with T-cell
receptor and co-culture with various concentrations of chrysotile fibers using
freshly isolated CD4+ surface CXCR3 positive and negative fractions, the
intracellular expression of CXCR3, IFNgamma and IL-17 remained unchanged when co
cultured with chrysotile. However, subsequent re-stimulation with phorbol 12
myristate 13-acetate (PMA) and ionomycin resulted in enhanced IL-17 production
and expression, particularly in CD4+ surface CXCR3 positive cells. These results
indicated that the balance and polarization between Treg and Th-17 fractions play
an important role with respect to the immunological effects of asbestos and the
associated reduction in antitumor immunity.
PMID- 28498410
TI - Neuropeptide Y suppresses epileptiform discharges by regulating AMPA receptor
GluR2 subunit in rat hippocampal neurons.
AB - The present study aimed to investigate the effects of neuropeptide Y (NPY) on the
alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor
glutamate receptor 2 (GluR2) subunit in epileptiform discharge hippocampal
neurons. Hippocampal neurons were harvested from neonatal Sprague-Dawley rats
aged <24 h and primarily cultured in vitro. At day 12 following culture,
hippocampal neurons were divided into the following groups: Control, Mg2+-free,
NPY+Mg2+-free and BIBP3226+NPY+Mg2+-free. The action potential of neurons was
measured using the whole cell patch clamp technique in the control, Mg2+-free and
NPY+Mg2+-free groups. AMPA current (IAMPA) was detected and peak current density
was calculated in each group. Alterations in total protein and phosphorylation of
the GluR2 subunit were detected by western blot analysis, and GluR2 mRNA
expression levels were detected by reverse transcription-quantitative polymerase
chain reaction, in each group. The whole cell patch clamp technique demonstrated
an abnormal action potential in the Mg2+-free group. The frequency and amplitude
of the action potential were significantly greater in the Mg2+-free group
compared with the control group, and significantly reduced in the NPY+Mg2+-free
group compared with the Mg2+-free group (P<0.05). In the Mg2+-free group,
compared with the control group, peak current density was significantly reduced
(P<0.05), GluR2 subunit protein content was slightly reduced (P>0.05),
phosphorylation levels of GluR2 subunit were significantly greater (P<0.05) and
GluR2 mRNA was significantly reduced (P<0.05). In the NPY+Mg2+-free group,
compared with the Mg2+-free group, peak current density was significantly greater
(P<0.05), phosphorylation levels of GluR2 subunit were significantly reduced
(P<0.05) and GluR2 mRNA expression was significantly greater (P<0.05). In the
BIBP3226+NPY+Mg2+-free group, compared with the NPY+Mg2+-free group, peak current
density was significantly reduced (P<0.05), phosphorylation levels of GluR2
subunit were significantly greater (P<0.05) and GluR2 mRNA expression was
significantly reduced (P<0.05). After 3 h of treatment with Mg2+-free
extracellular fluid, epileptiform discharge was detected in the cells. NPY
inhibited the discharge and its underlying mechanism may be that epileptiform
discharge suppressed the function of the AMPA receptor GluR2 subunit. NPY
relieved the inhibition of the GluR2 subunit via the Y1 receptor. This may
provide a novel direction for future studies on the pathogenesis and treatment of
epilepsy.
PMID- 28498409
TI - Demonstration of a potent RET transcriptional inhibitor for the treatment of
medullary thyroid carcinoma based on an ellipticine derivative.
AB - Dominant-activating mutations in the RET (rearranged during transfection) proto
oncogene, which encodes a receptor tyrosine kinase, is often associated with the
development of medullary thyroid carcinoma (MTC). The proximal promoter region of
the RET gene consists of a guanine-rich sequence containing five runs of three
consecutive guanine residues that serve as the binding site for transcriptional
factors. As we have recently shown, this stretch of nucleotides in the promoter
region is highly dynamic in nature and tend to form non-B DNA secondary
structures called G-quadruplexes, which suppress the transcription of the RET
gene. In the present study, ellipticine and its derivatives were identified as
excellent RET G-quadruplex stabilizing agents. Circular dichroism (CD)
spectroscopic studies revealed that the incorporation of a piperidine ring in an
ellipticine derivative, NSC311153 improves its binding with the G-quadruplex
structure and the stability induced by this compound is more potent than
ellipticine. Furthermore, this compound also interfered with the transcriptional
mechanism of the RET gene in an MTC derived cell line, TT cells and significantly
decreased the endogenous RET protein expression. We demonstrated the specificity
of NSC311153 by using papillary thyroid carcinoma (PTC) cells, the TPC1 cell line
which lacks the G-quadruplex forming sequence in the promoter region due to
chromosomal rearrangement. The RET downregulation selectively suppresses cell
proliferation by inhibiting the intracellular Raf/MEK/ERK and PI3K/Akt/mTOR
signaling pathways in the TT cells. In the present study, we also showed that the
systemic administration of a water soluble NSC311153 analog in a mouse MTC
xenograft model inhibited the tumor growth through RET downregulation.
PMID- 28498411
TI - Mitochondrial activity and oxidative stress functions are influenced by the
activation of AhR-induced CYP1A1 overexpression in cardiomyocytes.
AB - There is an endemic cardiomyopathy currently occurring in China, termed, Keshan
disease (KD). The authors previously compared mitochondrial-associated gene
expression profiles of peripheral blood mononuclear cells (PBMCs) derived from KD
patients and normal controls, using mitochondria-focused cDNA microarray
technology. The results detected an upregulation of the enzyme-associated CYP1A1
gene, (ratios >=2.0). The aryl hydrocarbon receptor (AhR) regulates the
expression of numerous cytochrome P450 (CYP) genes including members of the CYP1
family; CYP1A1 and CYP1A2. Several previous studies have suggested roles for the
aryl hydrocarbon receptor (AhR) and the genes that it regulates. An example
involves cytochrome P4501A1 (CYP1A1), in the pathogenesis of heart failure,
cardiac hypertrophy and other cardiomyopathies. Mitochondria comprise ~30% of the
intracellular volume in mammalian cardiomyocytes, and subtle alterations in
mitochondria can markedly influence cardiomyopathies. The present study
investigated alterations in the activity and functions of mitochondria following
AhR-induced overexpression of CYP1A1. AC16 cells were treated with the CYP1A1
inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and cytotoxicity was then
evaluated in MTT assays. Reverse transcription-quantitative polymerase chain
reactions, western blot analysis and 7-ethoxyresorufin O-deacylase assays were
performed to analyze the mRNA and protein levels, and the enzymatic activity of
CYP1A1. Mitochondrial activity and mass were analyzed using an inverted
fluorescence microscope and a fluorescence microplate reader. Reactive oxygen
species (ROS) activity was analyzed using flow cytometry. The results of the
current study demonstrated that TCDD gradually increased mRNA and protein levels
of AhR and CYP1A1, in addition to the enzymatic activity. Mitochondrial activity
and the quality of mitochondrial membranes were also significantly attenuated,
and mitochondrial ROS levels were elevated in the TCDD-induced cardiomyocytes.
The results indicate the involvement of the AhR/CYP1A1 signaling pathway in the
mechanism of action of TCDD in human cardiomyocytes. The present findings may
provide an explanation for myocardial injuries caused by polycyclic aromatic
hydrocarbons. The authors conclude that exposure to TCDD results in regulatory
alteration to the expression of detoxification genes that ultimately affect the
metabolic activation and function of cardiomyocytes.
PMID- 28498412
TI - Emmprin, released as a microvesicle in epithelioid sarcoma, interacts with
fibroblasts.
AB - Emmprin (extracellular matrix metalloproteinase inducer, CD147) is a glycosylated
transmembrane protein, consisting of two immunoglobulin domains, that stimulates
the production of matrix metalloproteinases (MMPs) by tumor-associated
fibroblasts. These effects play important roles in tumor invasion and metastasis.
However, the precise mechanisms by which emmprin acts on fibroblasts have not
been fully elucidated, especially in sarcoma cells. Previously, we demonstrated
that emmprin, expressed in conditioned medium collected from the epithelioid
sarcoma cell line (FU-EPS-1), stimulates MMP-2 production via interactions with
fibroblasts. In this study, we used microvesicles derived from sarcoma cells, and
determined whether emmprin exists in the microvesicles, which enhance the
production of MMP-2 via fibroblasts. Microvesicles released from FU-EPS-1 cells
were shown to contain full-length emmprin, identified as a 45-kDa protein
characterized by polylactosamine glycosylation. Microvesicles collected from FU
EPS-1 cells transfected with emmprin-specific siRNA or transduced with shRNA
displayed significantly reduced MMP-2 production by fibroblasts compared with
those from control-transfected cells. Our findings show that emmprin is released
through microvesicle shedding in sarcoma cells, and emmprin in microvesicles
regulates MMP-2 production by influencing the activity of fibroblasts located at
sites distant from the tumor cells.
PMID- 28498413
TI - CpG oligodeoxynucleotides augment antitumor efficacy of folate receptor alpha
based DNA vaccine.
AB - Folate receptor alpha (FRalpha) is overexpressed in a variety of solid tumors and
has become an attractive target antigen for immunotherapy purposes. A DNA vaccine
was generated by ligation of FRalpha cDNA into the eukaryotic vector pcDNA3.1.
Expression of FRalpha was confirmed in transiently transfected B16 cells. B16
cell lines that stably express FRalpha were set up by G418 selection. A total of
100 ug purified plasmid DNA alone or in combination with CpG
oligodeoxynucleotides (CpG ODN) was injected intramuscularly in C57BL/6 mice four
times at one week intervals. ELISA analysis confirmed that high titers of
antibodies against FRalpha existed in the sera of the experimental animals.
Specific cytotoxic T lymphocyte activity against FRalpha-expressing B16 cells was
found and FRalpha specific lymphocyte proliferation was detected. Coinjection of
CpG ODN increased both humoral and cellular immune responses. In the protective
model, in which C57BL/6 mice were immunized with the FRalpha DNA vaccine four
weeks before tumor cell inoculation, the growth of tumor was significantly
inhibited, and the presence of CpG ODN further increased the inhibitory effect.
FRalpha DNA vaccine alone did not show a significant inhibitory effect in the
therapeutic model, in which the DNA vaccine was immediately injected after tumor
inoculation. However, FRalpha DNA vaccine plus CpG ODN showed a significant
inhibitory effect in tumor growth. Survival curves for both animal experiments
confirmed that mice immunized with pcDNA3.1/FRalpha plus CpG ODN had a
significantly prolonged survival period than that of the pcDNA3.1 control group,
the CpG ODN group or the pcDNA3.1/FRalpha group. The above showed that human
FRalpha based DNA vaccination with CpG ODN as an adjuvant was effective in growth
inhibition of a FRalpha expressing tumor in mice and deserves further evaluation
as a possible immunotherapy.
PMID- 28498414
TI - Nifuroxazide prompts antitumor immune response of TCL-loaded DC in mice with
orthotopically-implanted hepatocarcinoma.
AB - Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with a poor
prognosis and high mortality. At present, vaccination with tumor cell lysate
(TCL) loaded dendritic cells (DC) has been shown to be an effective therapy
against HCC. However, the ability of promoting the specific T cell immune
response is rather weak, influencing the antitumor response. Thus, it is
necessary to find a strategy to improve the antitumor effect of TCL-loaded DC.
Activation of signal transducer and activator of transcription 3 (STAT3)
significantly inhibits antitumor immune response and DC maturity. Nifuroxazide,
an antidiarrheal agent, has been proved to directly inhibit STAT3 activation.
Thus, we investigated whether nifuroxazide could improve the antitumor immune
response in mice vaccinated with TCL-loaded DC. The study provides the
theoretical and experimental basis for developing an effective adjuvant for DC
vaccine to treat HCC. Our results showed that the administration of nifuroxazide
and DC-loaded TCL could significantly improve the survival rate, inhibit the
tumor growth, and prompt the antitumor immune responses in mice with
orthotopically implanted hepatocarcinomas, thus, possibly providing a new
combination strategy to treat HCC.
PMID- 28498416
TI - Association of long-chain acyl-coenzyme A synthetase 5 expression in human breast
cancer by estrogen receptor status and its clinical significance.
AB - The lipid metabolic enzymes are considered candidate therapeutic targets for
breast cancer. Long-chain acyl-coenzyme A (CoA) synthase (ACSL) is one of lipid
metabolic enzymes and converts free-fatty acid to fatty acid-CoA. Five ACSL
isoforms including ACSL1, ACSL3, ACSL4, ACSL5 and ACSL6 are identified in human.
High ACSL4 expression has been observed in aggressive breast cancer phenotype.
However, the role of other isoforms is still little-known. We therefore, analyzed
the expression of ACSL isoforms in each subtype of breast cancer within METABRIC
dataset and cancer cell line encyclopedia dataset. The expression levels of
ACSL1, ACSL4 and ACSL5 in estrogen receptor (ER)-negative group were higher than
that in ER-positive group. Similar expression pattern was detected among breast
cancer cell lines MCF-7 (ER-positive) and MDA-MB-231 (ER-negative). Treatment of
ACSL inhibitor triacsin C which inhibited enzyme activity of ACSL 1, 3, 4 and 5
suppressed cell growth of MCF-7 and MDA-MB-231. Our results further showed that
high ACSL5 expression was associated with good prognosis in patients with both ER
positive and ER-negative breast cancer through KM plotter analysis. These results
suggest that ACSL1, ACSL4 and ACSL5 expression is regulated by ER signaling
pathways and ACSL5 is a potential novel biomarker for predicting prognosis of
breast cancer patients.
PMID- 28498415
TI - Downregulated connexin32 promotes EMT through the Wnt/beta-catenin pathway by
targeting Snail expression in hepatocellular carcinoma.
AB - Hepatocellular carcinoma (HCC) is one of the common malignances in the world and
is associated with high mortality and poor prognosis, partly due to early
invasion and metastasis. Cx32 has been indicated to be involved in the
progression of many cancers including HCC, but its relationship with tumor
invasion and metastasis is still controversial. In the present study, the
downregulated Cx32 in HCC tissue was found negatively correlated with
histological grade and lymph node metastasis. Cx32 regulated HCC migration and
invasion in vitro and inhibited tumor metastasis in xenograft models in vivo. We
subsequently identified that Cx32 mediated epithelial-mesenchymal transition
(EMT) by regulating Snail expression, and the enhanced Snail was due to
activation of Wnt/beta-catenin signaling in response to Cx32 inhibition. Finally,
decreased expression of Cx32 showed strong correlation with loss/reduction of E
cadherin, higher expression of Snail, and nuclear accumulation of beta-catenin in
HCC tissues. Taken together, our results suggest that Cx32 inhibits HCC invasion
and metastasis through Snail-mediated EMT, Cx32 and this signaling pathway
molecules may offer potential targets for HCC cancer therapy.
PMID- 28498417
TI - CENP-H regulates the cell growth of human hepatocellular carcinoma cells through
the mitochondrial apoptotic pathway.
AB - The genomic alterations of hepatocellular carcinoma (HCC) are still unclear.
Centromere protein-H (CENP-H) has been shown to be associated with many solid
tumors. Our previous study found that CENP-H was upregulated in HCC and was
related to patient prognosis. However, the biological functions of CENP-H in HCC
and the possible underlying mechanisms have not been well elucidated. In the
present study, we demonstrated that CENP-H knockdown inhibited the proliferation
of Hep3B cells and decreased colony formation ability of single cells in vitro.
Furthermore, CENP-H knockdown induced Hep3B cell apoptosis, and apoptotic bodies
were observed using transmission electron microscopy. The protein expression of
cleaved caspase-3 was upregulated in Hep3B cells after CENP-H knockdown.
Additionally, a Bax/Bcl-2 ratio imbalance with a significant increase of Bax and
a substantial decrease of Bcl-2 at both the mRNA and protein levels were
determined in this study. In an animal experiment, CENP-H knockdown blocked the
growth of Hep3B subcutaneous xenografts. Immunohistochemistry revealed that the
protein expression of cleaved caspase-3 and Bax was increased, whereas the
protein expression of Bcl-2 and Ki-67 was decreased in subcutaneous xenografts of
the CENP-H-knockdown group. In summary, CENP-H may be involved in cell
proliferation and apoptosis of HCC cells through the mitochondrial apoptotic
pathway. Combined with previous studies, the data provide a new perspective on
HCC development and progression.
PMID- 28498418
TI - Identification and expression of MMSA-8, and its clinical significance in
multiple myeloma.
AB - In our previous studies, we identified 12 multiple myeloma (MM)-associated
antigens by serological analysis of tumor-associated antigens with a recombinant
cDNA expression library (SEREX) on MM. MM-associated antigen-8 (MMSA-8) was one
of the new antigens identified. We determined the 3'- and 5'-ends of MMSA-8 using
SMART-rapid amplification of cDNA ends (RACE) and then cloned its full-length
cDNA in the U266 cell line. The full cDNA sequence revealed that MMSA-8 is RPS27A
related transcript variant 1 that is specifically associated with MM. We examined
its prognostic significance for the first time, by investigating the correlations
between MMSA-8 expression and definite clinicopathological features. We
quantitatively assessed MMSA-8 expression using qRT-PCR and western blot analysis
in healthy donors and MM patients. The expression levels of MMSA-8 were
upregulated with statistical significance in MM patients in contrast to those in
healthy donors. The expression of MMSA-8 was also upregulated in relapsed
patients compared with that in the complete remission (CR) group. Contrasting
MMSA-8 expression levels in different patients with definite clinicopathological
features suggested an association between MMSA-8 with unfavorable
clinicopathological characteristics, such as international staging system (ISS)
stage III, higher lactate dehydrogenase (LDH) levels and higher C-reactive
protein (CRP) levels. The expression of MMSA-8 was also increased in patients
with unfavorable cytogenetic and genetic abnormalities, including the presence of
t(11;14), t(4;14), t(14;16), del(17p), del(13q) and p53 deletion, which was
statistically significant. The expression of MMSA-8 exhibited significant
variance in the treatment responses of the CR, PR, progression and relapse
groups. Univariate and multivariate analyses revealed that high MMSA-8 values
were associated with poorer progression-free survival (PFS) and overall survival
(OS) in MM patients independently. In conclusion, our data indicated that MMSA-8
is an independent and unfavorable prognostic risk factor in MM; MMSA-8 is also a
promising diagnostic and therapeutic target in MM patients, but further
validation is needed.
PMID- 28498420
TI - CRISPR/Cas9-mediated genome engineering of CXCR4 decreases the malignancy of
hepatocellular carcinoma cells in vitro and in vivo.
AB - CXC chemokine receptor 4 (CXCR4) is associated with poor clinical outcomes and
decreased survival in hepatocellular carcinoma (HCC). In the present study, we
targeted CXCR4 by CRISPR/Cas9 in HepG2 cells and observed the effects both in
vitro and in vivo. The results indicated that after targeting CXCR4 the
expression of CXCR4 was significantly decreased and the cell proliferation was
inhibited. Clonogenicity and scratch cell migration assays indicated that
specific downregulation of CXCR4 inhibited cell migration. This disruption of
CXCR4 led to less invasiveness, the genes related to epithelial-mesenchymal
transition (EMT) and cell self-renewal were also affected. Moreover, sensitivity
to the anticancer drug cisplatin was significantly increased in vitro by the
downregulation of CXCR4. The results of the in vivo study showed that the growth
volumes were significantly smaller in neoplasms derived from CXCR4-downregulated
HepG2 cells compared to those derived from wild-type cells. These results showed
that targeting CXCR4 by CRISPR/Cas9 could inhibit proliferation, migration and
invasion, reversed EMT, increased chemosensitivity and decrease the malignancy of
HCC in vitro and in vivo.
PMID- 28498419
TI - miR-590 regulates WT1 during proliferation of G401 cells.
AB - Nephroblastoma (Wilms' tumor) is frequently associated with mortality in
children. MicroRNAs (miRNAs) are important for tumor development serving as
oncogenes or tumor suppressors. In the present study, miRNA-590 (miR-590) was
identified to be upregulated in Wilms' tumor tissues compared with the normal
adjacent tissues. Additionally, the levels of miR-590 were consistent with their
clinical stage. Wilms' tumor 1 (WT1) was considered to be a tumor suppressor in
certain tumor types, and it has been detected at low expression levels in various
types of cancer with high cell proliferation and aggressive behavior. The
expression levels of miR-590 were quantified using reverse transcription
quantitative polymerase chain reaction. Cell proliferation was measured using 5
ethynyl-20-deoxyuridine assays. The protein expression levels of WT1 were
investigated by western blot analysis. To the best of our knowledge, the present
study was the first to determine that WT1 was a target gene of miR-590 as miR-590
was able to negatively regulate WT1 expression level by binding to the specific
target site within the 3'-untranslated region (3'-UTR) of WT1 in G401 cells.
Additionally, overexpression of miR-590 promoted G401 cell proliferation which
was consistent with the effect of small interfering RNA-WT1. Subsequently, the
present study determined that the cell phenotype altered by miR-590
overexpression may be reversed by upregulation of WT1 in G401 cells. In
conclusion, the observations indicated that miR-590 may function as an oncogene
via targeting WT1 to induce G401 cell proliferation. These results may contribute
to current understanding of the function of miR-590 in nephroblastoma.
PMID- 28498421
TI - Molecular analysis of the mouse brain exposed to chronic mild stress: The
influence of hepatocyte nuclear factor 4alpha on physiological homeostasis.
AB - Major depressive disorder (MDD) is a prevalent disorder that causes considerable
disability in social functioning and is a risk factor for physical diseases.
Recent clinical reports have demonstrated a marked association between MDD and
physiological dyshomeostasis induced by metabolic disorders, including diabetes,
hormone abnormalities and autoimmune diseases. The authors of the present study
have previously analyzed comparative gene expression profiles in the prefrontal
cortex (PFC) of a chronic mild stress (CMS) animal model of MDD. Hepatocyte
nuclear factor 4alpha (Hnf4alpha) was identified as a central regulator that
exerted significant influence on genes associated with physiological homeostasis.
The aim of the present study was to investigate: i) the molecular mechanism of
the depressive state in the PFC, and ii) the involvement of genes extracted from
the comparative gene expression profiles, particularly those applicable to MDD in
clinical practice. Core analysis of the previous PFC microarray results was
performed using Ingenuity Pathway Analysis (IPA). Subsequently, IPA was used to
search for molecules that are regulated by Hnf4alpha, and exist in the PFC and
serum. From the core analysis, 5 genes that are associated with cell death and
are expressed in the cortex were selected. Four of the extracted genes, insulin
like growth factor 1, transthyretin, serpin family A member 3 and plasminogen,
were markedly affected by Hnf4alpha. S100 calcium-binding protein A9 (S100a9) and
alpha2-HS-glycoprotein (Ahsg) were also chosen as they exist in serum and are
also affected by Hnf4alpha. A significant group difference in the expression of
these two genes was detected in the PFC, thalamus and hippocampus. The protein
levels of AHSG and S100A9 in the PFC and hippocampus of the CMS group increased
significantly when compared with the control group. These findings support the
close association of Hnf4alpha (through genes such as S100a9 and Ahsg) with the
development of various diseases induced by deregulation of physiological
homeostasis during the progression of MDD.
PMID- 28498422
TI - Garlic extract in bladder cancer prevention: Evidence from T24 bladder cancer
cell xenograft model, tissue microarray, and gene network analysis.
AB - There is a growing interest in the use of naturally occurring agents in cancer
prevention. This study investigated the garlic extract affects in bladder cancer
(BC) prevention. The effect of garlic extract in cancer prevention was evaluated
using the T24 BC BALB/C-nude mouse xenograft model. Microarray analysis of
tissues was performed to identify differences in gene expression between garlic
extract intake and control diet, and gene network analysis was performed to
assess candidate mechanisms of action. Furthermore, we investigated the
expression value of selected genes in the data of 165 BC patients. Compared to
the control group, significant differences in tumor volume and tumor weight were
observed in the groups fed 20 mg/kg (p<0.05), 200 mg/kg, and 1000 mg/kg of garlic
extract (p<0.01). Genes (645) were identified as cancer prevention-related genes
(fold change >2 and p<0.05) by tissue microarray analysis. A gene network
analysis of 279 of these genes (p<0.01) was performed using Cytoscape/ClueGo
software: 36 genes and 37 gene ontologies were mapped to gene networks. Protein
kinase A (PKA) signaling pathway including AKAP12, RDX, and RAB13 genes were
identified as potential mechanisms for the activity of garlic extract in cancer
prevention. In BC patients, AKAP12 and RDX were decreased but, RAB13 was
increased. Oral garlic extract has strong cancer prevention activity in vivo and
an acceptable safety profile. PKA signaling process, especially increasing AKAP12
and RDX and decreasing RAB13, are candidate pathways that may mediate this
prevention effect.
PMID- 28498423
TI - PCDH10 gene inhibits cell proliferation and induces cell apoptosis by inhibiting
the PI3K/Akt signaling pathway in hepatocellular carcinoma cells.
AB - Protocadherin10 (PCDH10), a member of the non-clustered protocadherin (PCDH)
family, functions as a tumor-suppressor gene in many cancers. Previous studies
have demonstrated that the expression of PCDH10 was noticeably downregulated in
the tissue and cells of hepatocellular carcinoma (HCC), when compared to those in
normal liver tissue. The decreased PCDH10 expression in HCC was correlated with
the aberrant methylation status of PCDH10 promoter. However, the biological
functions and molecular mechanism of PCDH10 in HCC have yet to be elucidated. The
aim of the present study was to identify the biological function and mechanisms
of PCDH10 in HCC. Quantitative real-time polymerase chain reaction was used to
detect the expression of PCDH10 in HCC cells with decreased expression of PCDH10
which were transfected with plasmid pcDNA3.1-PCDH10 or pcDNA3.1-vector using
Lipofectamine 2000. The biological effects of PCDH10 in HCC cells were detected
by CCK-8, colony formation and flow cytometric assays. Western blot and co
immunoprecipitation (Co-IP) assays were performed to explore the mechanism of
PCDH10 in HCC cells. PCDH10 expression was downregulated in the HCC cells (HepG2,
HuH7, HuH1, and SNU387) when compared to the normal liver cells (L02).
Upregulation of PCDH10 inhibited cell proliferation and induced cell apoptosis in
the HCC cells. More importantly, we revealed that PCDH10 inhibited the PI3K/Akt
signaling pathway thus carrying out its suppressive function in HCC. This study
provides insights into the tumorigenesis and progression of HCC, and puts forward
the novel hypothesis that PCDH10 could be a new biomarker for HCC, or that
combined with other molecular markers could increase the specificity and
sensitivity of diagnostic tests for HCC. Restoration of PCDH10 could be a
valuable therapeutic target for HCC.
PMID- 28498424
TI - MicroRNA-15b promotes proliferation and invasion of non-small cell lung carcinoma
cells by directly targeting TIMP2.
AB - MicroRNA-15b (miR-15b) plays an important role in tumor development and
progression. miR-15b functions differently in various types of malignant tumors.
However, the expression pattern and role of miR-15b in non-small cell lung cancer
(NSCLC) have not been elucidated. In the present study, we investigated the
effect of miR-15b on the occurrence and development of lung cancer and the
underlying mechanism. Lung cancer cell lines A549 and LTEP-a-2 were transfected
with miR-15b inhibitor or mimic, respectively. Real-time PCR revealed that the
expression level of miR-15b was significantly higher in human NSCLC tissues and
NSCLC cells, than that of normal tissues and cells, respectively (P<0.05).
Moreover, the effect of miR-15b on A549 and LTEP-a-2 cell viability, cell cycle,
migration and invasion was further evaluated. Experiments indicated that miR-15b
knockdown inhibited the viability, cell cycle, migration and invasion in A549
cells, while upregulation of miR-15b exhibited the opposite effect. Tissue
inhibitor of metallopeptidases 2 (TIMP2) protein and mRNA levels were
downregulated after miR-15b overexpression in A549 and LTEP-a-2 cells,
respectively. The dual-luciferase reporter gene assay implied that TIMP2 is a
direct target gene of miR-15b. Our results indicate that high expression of miR
15b is associated with NSCLC and suggest that miR-15b expression may be a novel
biomarker for predicting clinical outcomes in NSCLC patients. The inhibition of
miR-15b may even provide helpful therapeutic strategies for the treatment of
NSCLC.
PMID- 28498425
TI - Gene silencing of indoleamine 2,3-dioxygenase hinders tumor growth through
angiogenesis inhibition.
AB - The significance of indoleamine 2,3-dioxygenase-1 (IDO1) has been studied in
various types of tumors, but the relationship between IDO1 and tumor angiogenesis
needs further delineation. We aimed to clarify the relationship between tumor
angiogenesis and IDO1 expression, and to explore the possibility of IDO1
targeting molecular therapy for lung cancer. For the first time, we found that
silencing the IDO1 gene using small interfering RNA (siRNA) inhibits in vitro
cancer cell invasion and migration. We further demonstrated that knockdown of
IDO1 decreased the formation of vasculogenic mimicry. In addition to these in
vitro findings, we also demonstrated that in vivo IDO1 gene silencing using short
hairpin RNA (shRNA) delayed tumor onset and inhibited tumor growth in the mouse
model. Immunostaining showed that IDO1 gene silencing inhibited tumor
angiogenesis. Moreover, the expression of IDO1 was associated with microvessel
density (MVD) labeled by CD34 and CD146. These findings indicate that IDO1 has
the potential to participate in or contribute to the formation of new
capillaries, supporting the applicability of IDO1-targeting molecular therapy in
lung cancer.
PMID- 28498426
TI - Identification of a missense HOXD13 mutation in a Chinese family with syndactyly
type I-c using exome sequencing.
AB - Syndactyly is one of the most common hereditary limb malformations, and is
characterized by the fusion of specific fingers and/or toes. Syndactyly type I-c
is associated with bilateral cutaneous or bony webbing of the third and fourth
fingers and occasionally of the third to fifth fingers, with normal feet. The aim
of the present study was to identify the genetic basis of syndactyly type I-c in
four generations of a Chinese Han family by exome sequencing. Exome sequencing
was conducted in the proband of the family, followed by direct sequencing of
other family members of the same ancestry, as well as 100 ethnically-matched,
unrelated normal controls. A missense mutation, c.917G>A (p.R306Q), was
identified in the homeobox D13 gene (HOXD13). Sanger sequencing verified the
presence of this mutation in all of the affected family members. By contrast,
this mutation was absent in the unaffected family members and the 100 ethnically
matched normal controls. The results suggest that the c.917G>A (p.R306Q) mutation
in the HOXD13 gene, may be responsible for syndactyly type I-c in this family.
Exome sequencing may therefore be a powerful tool for identifying mutations
associated with syndactyly, which is a disorder with high genetic and clinical
heterogeneity. The results provide novel insights into the etiology and diagnosis
of syndactyly, and may influence genetic counseling and the clinical management
of the disease.
PMID- 28498427
TI - Effect of macrophages on breast cancer cell proliferation, and on expression of
hormone receptors, uPAR and HER-2.
AB - Malignant tumors, including breast cancers, are frequently infiltrated with
innate immune cells and tumor-associated macrophages (TAMs) represent the major
inflammatory component in stroma of many tumors. In this study, we examined the
immunoreactivity of the macrophage markers CD68 and CD163 as well as the hormone
receptors estrogen receptor alpha (ERalpha), progesterone receptor (PR), estrogen
receptor beta1 (ERbeta1), human epidermal growth factor receptor 2 (HER-2),
matrix metalloproteinase 9 (MMP-9), urokinase-type plasminogen activator receptor
(uPAR) and the proliferations marker Ki67 in 17 breast cancer biopsies. The
quantitative score for CD68+ and CD163+ strongly indicate M2 phenotype dominance
in the currently investigated biopsies. We found that an increasing level of
macrophages was negatively associated with ERalpha or PR, whereas a positive
association was observed for Ki-67 or uPAR. No significant association could be
seen between the level of macrophage and HER-2, ERbeta1 or MMP-9 expression.
Effect of conditioned media (CM) generated from cultured human M1 and M2
macrophage phenotypes were investigated on the proliferation and expression of
selected markers in the T47D breast cancer cell line. We found that in contrast
to the in vivo situation, in particularly the CM from M1 macrophages decreased
the growth and Ki67 expression in T47D, and significantly increased ERbeta1 mRNA
levels. Moreover, in accordance to the in vivo situation the CM from the
macrophages decreased the expression of ERalpha protein as well as ERalpha or PR
mRNA. In conclusion our results show that macrophages alone have the capability
to decrease the tumor cell expression of ERalpha and PR in vitro. In the tumor
environment in vivo macrophages also contribute to an increase in tumor cell
expression of uPAR and Ki67, suggesting that macrophages are involved in
impairing the prognosis for breast cancer patients.
PMID- 28498428
TI - Differential expression profiles of microRNAs as potential biomarkers for the
early diagnosis of lung cancer.
AB - Lung cancer is one of the most lethal malignancies worldwide. To reduce the high
morbidity and mortality of the disease, sensitive and specific biomarkers for
early detection are urgently needed. Tumor-specific microRNAs (miRNAs) seem to be
potential biomarkers for the early diagnosis and treatment of cancer. In this
study, the microarray of miRNAs and mRNAs on the same samples was performed and
the intersection taken with The Cancer Genome Atlas (TCGA) lung cancer
miRNA/RNAseq dataset. Then, miRNA-mRNA regulatory network was constructed to
identify miRNA candidates associated with lung cancer through integrating gene
expression and miRNA-target prediction. Furthermore, the expression levels of
miRNA candidates were validated by stem-loop real-time reverse transcription PCR
(qRT-PCR) in larger lung cancer population. The relationship between signature
miRNAs and the risk of lung cancer were assessed by conditional logistic
regression analysis. Diagnostic value of these miRNAs was determined by areas
under receiver operating characteristic curves (ROC). The Affymetrix microarray
analysis identified a total of 116 miRNAs and 502 mRNAs that could distinguish
lung tumor tissues from adjacent non-tumor tissues, of which 70 miRNAs and 136
mRNAs were upregulated, while 46 miRNAs and 366 mRNAs were downregulated,
respectively. In combination with TCGA analysis, we identified 32 miRNAs and 377
mRNAs related to lung cancer. Then, 28 key miRNAs related to 61 inter-section
mRNAs were identified by miRNA-mRNA network analysis. The miRNA function analysis
was indicative of that 18 upregulated and 10 downregulated miRNAs involved in
signaling pathways related to Environmental Information Processing and Human
Diseases. Population result showed that the expression of 7 miRNAs (miR-205-5p,
miR-3917, miR-30a-3p, miR-30a-5p, miR-30c-2-3p, miR-30d-5p and miR-27a-5p) was
consistent with the analysis result of microarray and TCGA. In addition,
upregulation of miR-205-5p, miR-3917 and downregulation of miR-30a-3p, miR-30a
5p, miR-30c-2-3p, miR-30d-5p, miR-27a-5p increased the risk of lung cancer by
conditional logistic regression analysis. The diagnostic accuracy of miR-205-5p,
miR-3917, miR-27a-5p, miR-30a-3p, miR-30a-5p, miR-30c-2-3p, miR-30d-5p showed
that their corresponding AUCs were 0.728, 0.661, 0.637, 0.758, 0.772, 0.734,
0.776, respectively. Therefore, there are a set of signature miRNAs which may be
promising biomarkers for the early screening of high-risk populations and early
diagnosis of lung cancer.
PMID- 28498429
TI - SBI0206965, a novel inhibitor of Ulk1, suppresses non-small cell lung cancer cell
growth by modulating both autophagy and apoptosis pathways.
AB - Lung cancer is a major public health problem worldwide. Non-small cell lung
cancer (NSCLC) accounts for 85% of lung cancer cases. Autophagy has recently
sparked great interest, and it is thought to participate in a variety of
diseases, including lung cancer. Uncoordinated (Unc) 51-like kinase 1 (Ulk1), a
serine/threonine kinase, plays a central role in the autophagy pathway. However,
the role of Ulk1 in NSCLC remains unclear. We report that NSCLC cell lines
exhibited high expression of Ulk1 and that Ulk1 was negatively correlated with
prognosis in lung cancer patients. Knockdown of Ulk1 or the inhibition of Ulk1 by
the selective inhibitor SBI0206965, inhibited cell proliferation, induced cell
apoptosis and enhanced the sensitivity of cisplatin against NSCLC cells.
Moreover, we demonstrated that Ulk1 exerted oncogenic activity in NSCLC by
modulating both autophagy and apoptosis pathways. Inhibition of autophagy by
SBI0206965 sensitized NSCLC cells to cisplatin by inhibiting cisplatin induced
cell-protective autophagy to promote apoptosis. Furthermore, SBI0206965 promoted
apoptosis in NSCLC cells independent of autophagy, which was partly mediated by
destabilization of Bcl2/Bclxl. In summary, our results show that inhibition of
Ulk1 suppresses NSCLC cell growth and sensitizes NSCLC cells to cisplatin by
modulating both autophagy and apoptosis pathways, and that Ulk1 might be a
promising target for NSCLC treatment.
PMID- 28498430
TI - UVA-induced upregulation of progerin suppresses 53BP1-mediated NHEJ DSB repair in
human keratinocytes via progerin-lamin A complex formation.
AB - Ultraviolet (UV) radiation is the primary risk factor underlying photoaging and
photocarcinogenesis. Mounting research has focused on the role of DNA damage
response pathways in UV-induced double-strand break (DSB) repair. In the present
study, we hypothesized that UVA-induced aberrant progerin upregulation may
adversely affect p53-binding protein 1 (53BP1)-mediated non-homologous end
joining (NHE) DSB repair in human keratinocytes. Basal cell carcinoma (BCC)
tumors and matching normal skin tissue were sampled (n=200) to investigate
whether human keratinocytes display dysregulated progerin expression as a
function of advancing age and BCC status. Newborn foreskin samples (n=9) were
used as a source for primary keratinocyte cultures. We investigated the effects
of UVA radiation on progerin and lamin A expression as well as the effects of the
silencing of progerin on lamin A protein expression in UVA-irradiated
keratinocytes. We investigated whether blocking progerin-lamin A interaction was
able to rescue UVA-induced lamin A protein downregulation, 53BP1 downregulation
and 53BP1-mediated NHEJ DSB repair activity. Progerin upregulation in adult
keratinocytes was associated with advancing age, not BCC status. In vitro, UVA
exposure significantly upregulated progerin expression by favoring alternative
LMNA gene transcript splicing. UVA exposure significantly downregulated free
(unbound) lamin A protein levels via progerin-lamin A complex formation. UVA
exposure significantly decreased 53BP1 protein levels via enhanced progerin-lamin
A complex formation. UVA-induced progerin-lamin A complex formation was largely
responsible for suppressing 53BP1-mediated NHEJ DSB repair activity. The present
study is the first to demonstrate that UVA-induced progerin upregulation
adversely affects 53BP1-mediated NHEJ DSB repair in human keratinocytes via
progerin-lamin A complex formation.
PMID- 28498431
TI - PRKDC regulates chemosensitivity and is a potential prognostic and predictive
marker of response to adjuvant chemotherapy in breast cancer patients.
AB - DNA-dependent kinase catalytic subunit (DNA-PKcs) is a critical component of DNA
repair machinery and is found to be up- or down-regulated in different cancer
types. However, its clinical significance in breast cancer remains unclear. To
this end, quantitative PCR was performed to measure PRKDC expression level in 59
pairs of breast cancer tissues and the non-tumor adjacent tissues (NATs). The
correlation between PRKDC expression and overall survival (OS) as well as the
prognostic value of PRKDC were analyzed. In vitro and in vivo effects of PRKDC on
chemosensitivity were evaluated in MCF-7 cells. We found that PRKDC expression
was significantly increased in breast cancer tissue samples compared with NATs.
High PRKDC expression was associated with higher tumor grade (P=0.001), positive
lymph node metastasis (P=0.0357) and chemoresistance (P=0.0006). Furthermore,
PRKDC expression was significantly correlated with OS in breast cancer patients
with (0.0101) or without (P=0.0216) receiving chemotherapy. PRKDC was an
independent prognostic factor of OS in breast cancer (P=0.022, hazard ratio=2.69,
95% confidence interval: 1.81-3.84). Moreover, downregulation of PRKDC sensitized
MCF-7 cells to chemo-drugs both in vitro and in a xenografted mouse model.
Collectively, our study demonstrated that PRKDC is a prognostic biomarker for
chemoresistance in breast cancer patients.
PMID- 28498432
TI - Time- and oxygen-dependent expression and regulation of NDRG1 in human brain
cancer cells.
AB - N-myc downstream-regulated gene 1 (NDRG1) is a tumor suppressor with the
potential to suppress metastasis, invasion and migration of cancer cells. It is
regulated under stress conditions such as starvation or hypoxia. NDRG1 regulation
is both induced and controlled by HIF-1alpha-dependent and -independent pathways
under hypoxic conditions. However, there are profound differences in the way
NDRG1 expression is regulated by HIF-1alpha and other transcription factors.
Therefore, we aimed to define the time-dependent pattern of NDRG1 mRNA and
protein expression in human glioblastoma cell lines in extreme hypoxia and after
re-oxygenation as well as under normoxic conditions. Furthermore, we ascribe the
regulation of NDRG1 to the transcription factors HIF-1alpha, SP1, CEBPalpha, YB-1
and Smad7 in a time-dependent manner. The human malignant glioma cell lines U87
MG, U373 and GaMG were cultured for 1, 6 and 24 h under hypoxic (0.1% O2)
conditions and then they were re-oxygenated. The mRNA expression of NDRG1, HIF
1alpha SP1, CEBPalpha, YB-1 and Smad7 was measured using semi-quantitative RT-PCR
analysis. Their protein expression was analyzed using western blotting. Our
experiments revealed that long-term (24 h), but not short-term hypoxia led to the
induction of NDRG1 expression in human glioma cell lines. NDRG1 expression was
found to correlate with the protein expression of HIF-1alpha, SP1, CEBPalpha, YB
1 and Smad7. The present study suggests for the first time that SP1 regulates
NDRG1 expression in glioma cells under hypoxia in a time-dependent manner along
with HIF-1alpha, CEBPalpha, YB-1 and Smad7. These molecules, each separately or
in combination, may possess the potential to become target molecules for
antitumor therapeutic approaches particularly in human brain tumors.
PMID- 28498433
TI - Curcumin induces apoptotic cell death and protective autophagy in human gastric
cancer cells.
AB - Curcumin possesses an anticancer effect against a wide assortment of tumors with
selective cytotoxicity for tumor cells. However, the mechanism involved in the
curcumin-induced anticancer effect remain unclear. In the present study, we
investigated the efficacy of curcumin against human gastric cancer cell growth
and the molecular mechanism involved. Our results demonstrated that curcumin
inhibited the viabilities of gastric cancer cell lines BGC-823, SGC-7901 and MKN
28 in both a time- and dose-dependent manner. In addition, curcumin treatment
induced gastric cancer cell apoptosis in a dose-responsive manner. Western
blotting of apoptosis-related proteins further confirmed the pro-apoptotic
potential of curcumin. After exposure to curcumin, a robust induction of
autophagy was observed in gastric cancer cells, which was characterized by the
formation of acidic vesicular organelles (AVOs), conversion of LC3-I to LC3-II
and an increase in the levels of autophagy-related proteins. Activation of the
PI3K/Akt/mTOR signaling pathway was suppressed in gastric cancer cells with
curcumin treatment. However, administration of the autophagy inhibitor 3
methyladenine (3-MA) significantly promoted the apoptotic cell death induced by
curcumin. Collectively, our findings provide new evidence that curcumin induces
apoptotic cell death and protective autophagy in human gastric cancer cells in
vitro. Autophagy inhibitor treatment may provide a novel and effective strategy
for improving the anticancer effect of curcumin against gastric cancer.
PMID- 28498434
TI - A ligand-based and enediyne-energized bispecific fusion protein targeting
epidermal growth factor receptor and insulin-like growth factor-1 receptor shows
potent antitumor efficacy against esophageal cancer.
AB - Recent studies have revealed that the epidermal growth factor receptor (EGFR) and
insulin-like growth factor-1 receptor (IGF-1R) are overexpressed in various types
of human tumors and are attractive targets for anticancer drugs. In the present
study, the expression of EGFR and IGF-1R in esophageal squamous cell carcinoma
(ESCC) and adjacent normal tissues in a tissue microarray was firstly detected by
immunohistochemical staining. In addition, their co-overexpression was observed
in 48 out of 75 (64%) patients. Based on the findings, the antitumor activity of
an EGFR/IGF-1R bispecific and enediyne-energized fusion protein EGF-LDP-IGF-AE,
which we constructed recently by fusing two ligands (EGF and IGF-1) with an
enediyne antibiotic lidamycin (LDM), on ESCC were evaluated. Binding assay
indicated that the EGF-LDP-IGF protein bound to esophageal cancer cells, and then
internalized into the cytoplasm. In vitro, the enediyne-energized fusion protein
EGF-LDP-IGF-AE exhibited extremely potent cytotoxicity to ESCC cells with IC50
values between 10-10 and 10-15 mol/l. In vivo, EGF-LDP-IGF-AE also markedly
suppressed the growth of human KYSE450 xenografts by 75.1% when administered at
0.3 mg/kg in a nude mouse model, and its efficacy was significantly higher than
that of LDM (at maximum tolerated dosage) and mono-specific counterparts. In
addition, EGF-LDP-IGF-AE arrested cell cycle progression and it concentration
dependently induced cell apoptosis as well as inhibited the activation of
EGFR/IGF-1R and two major downstream signaling pathways (PI3K/AKT and RAS/MAPK).
These data imply the potential clinical application of EGF-LDP-IGF-AE for ESCC
patients with EGFR and/or IGF-1R overexpression.
PMID- 28498435
TI - Plumbagin enhances TRAIL-induced apoptosis of human leukemic Kasumi-1 cells
through upregulation of TRAIL death receptor expression, activation of caspase-8
and inhibition of cFLIP.
AB - Although the patients with t(8;21) acute myeloid leukemia (AML) have a favorable
prognosis compared with other non-acute promyelocytic leukemia AML patients, only
~50% patients with this relatively favorable subtype can survive for 5 years and
refractory/relapse is common in clinical practice. So it is necessary to find
novel agents to treat this type of AML. In this study, the effects and the
mechanisms of plumbagin and recombinant soluble tumor necrosis factor-alpha
related apoptosis-inducing ligand (rsTRAIL) on leukemic Kasumi-1 cells were
primarily investigated. Plumbagin and/or rsTRAIL could significantly inhibit the
growth of Kasumi-1 cells and induce apoptosis in vitro and in vivo. Plumbagin
enhanced TRAIL-induced apoptosis of Kasumi-1 cells in association with
mitochondria damage, caspase activation, upregulation of death receptors (DRs)
and decreased cFLIP expression. The effects of plumbagin on the expression of
DR5, Bax and cFLIP could be partially abolished by the reactive oxygen species
(ROS) scavenger NAC. Glutathione (GSH) depletion by plumbagin increased the
production of ROS. In vivo, there was no obvious toxic pathologic change in the
heart, liver and kidney tissues in any of the groups. Comparing with the control
mice, a significantly increased number of apoptotic cells were observed in the
combined treated mice by flow cytometry. Plumbagin also increased the expression
of DR4 and DR5 in cells of xenograft tumors. Collectively, our results suggest
that both plumbagin and rsTRAIL could be used as a single agent or synergistical
agents to induce apoptosis of leukemic Kasumi-1 cells in vitro and in vivo.
PMID- 28498436
TI - Exposure to a chronic high-fat diet promotes atrial structure and gap junction
remodeling in rats.
AB - Obesity has been demonstrated to be linked to atrial fibrillation (AF) with
atrial enlargement and tissue fibrosis. Long-term high calorie intake is the main
reason for the prevalence of obesity. To investigate the possible causes of AF,
such as chronic high-fat diet (HFD), and to identify the underlying mechanisms,
the present study analyzed a variety of structural and gap junctional
electrophysiological alterations in the atria of female rats fed an HFD. After
consistent HFD feeding of female rats for 12 weeks, hematoxylin and eosin (H&E)
and Masson's staining, RT-qPCR, western blotting, immunofluorescence and TUNEL
staining were performed. In our study, approximately 3/5 of the HFD-fed rats (HFD
OB, n=13) displayed a significant increase in body weight, while the other 2/5
did not (HFD-NOB, n=8). In addition, the atrial weight of the HFD-OB and HFD-NOB
rats was markedly heavier, as compared to the rats fed a normal diet (CT, n=20).
According to the plasma lipid levels, both HFD-OB and HFD-NOB rats exhibited
dyslipidemia. Furthermore, H&E staining revealed broadened interstitial space and
myocyte disarray in atria of the HFD-fed rats (i.e., HFD-OB and HFD-NOB rats).
Expression levels of atrial fibrosis relevant factors, transforming growth factor
beta1 and matrix metalloproteinase-2, were significantly upregulated in the HFD
fed rat atria. In addition, we found a gap junction remodeling with distinct
alterations in expression and distribution of connexin 40 (Cx40) and Cx43 in the
HFD-fed rat atria. Moreover, a modest increase in apoptotic cell death in both
the HFD-OB and HFD-NOB rat atria was detected. Taken together, our findings
demonstrated that the impact of chronic HFD on atria displayed in the diet
induced obese rats was observed in HFD-fed rats in the absence of obesity as
well.
PMID- 28498437
TI - Autocrine expression of the epidermal growth factor receptor ligand heparin
binding EGF-like growth factor in cervical cancer.
AB - In cervical cancer, the epidermal growth factor receptor (EGFR) is overexpressed
in 70-90% of the cases and has been associated with poor prognosis. EGFR-based
therapy is currently being explored in cervical cancer. We investigated which
EGFR ligand is primarily expressed in cervical cancer and which cell type
functions as the major source of this ligand. We hypothesized that macrophages
are the main source of EGFR ligands and that a paracrine loop between tumor cells
and macrophages is responsible for ligand expression. mRNA expression analysis
was performed on 32 cervical cancer cases to determine the expression of the EGFR
ligands amphiregulin, beta-cellulin, epidermal growth factor (EGF), epiregulin,
heparin-binding EGF-like growth factor (HB-EGF) and transforming growth factor
alpha (TGFalpha). Subsequently, protein expression was determined
immunohistochemically on 36 additional cases. To assess whether macrophages are
the major source of EGFR ligands, immunohistochemical double staining was
performed on four representative tissue slides. Expression of the chemokines
granulocyte-macrophage colony-stimulating factor (GM-CSF) and C-C motif ligand 2
(CCL2) was determined by mRNA in situ hybridization. Of the known EGFR ligands,
HB-EGF had the highest mRNA expression and HB-EGF and EGFR protein expression
were highly correlated. Tumor specimens with high EGFR expression showed higher
numbers of macrophages, and higher expression of GM-CSF and CCL2, but only a
small subset (9%) of macrophages was found to be HB-EGF-positive. Strikingly, 78%
of cervical cancer specimens were found to express HB-EGF. Standardized
assessment of staining intensity, using spectral imaging analysis, showed that HB
EGF expression was higher in the tumor compartment than in the stromal
compartment. These results suggest that HB-EGF is an important EGFR ligand in
cervical cancer and that cervical cancer cells are the predominant source of HB
EGF. Therefore, we propose an autocrine EGFR stimulation model in cervical
carcinomas.
PMID- 28498438
TI - Dexamethasone reduces side population fraction through downregulation of ABCG2
transporter in MCF-7 breast cancer cells.
AB - Side population (SP) cells represent a rare population among breast cancer cells.
SP cells have been reported to act as cancer stem-like cells, and to participate
in the development of multidrug resistance via modulating the expression of ATP
binding cassette subfamily G member 2 (ABCG2). Dexamethasone is a corticosteroid
drug that has been used as an adjuvant treatment to enhance the efficacy of
chemotherapeutic agents; however, its effects in breast cancer have yet to be
thoroughly investigated. In the present study, the effects of dexamethasone were
investigated using the human MCF-7 breast cancer cell line, and SPs were examined
in detail. Cellular proliferation, SP fractions and ABCG2 expression were
examined following treatment of MCF-7 cells with dexamethasone. Dexamethasone was
revealed to cause a dose- and time-dependent decrease in cancer cell
proliferation, and it also decreased the size of the SP fraction of MCF-7 cells
and the expression of the ABCG2 transporter. The effects of dexamethasone on
cellular proliferation, SP fraction and ABCG2 expression were abolished following
the administration of the glucocorticoid antagonist RU486. These results
suggested that dexamethasone may target breast cancer cell SPs and thus increase
the sensitivity of tumor cells to chemotherapy. Therefore, it may be hypothesized
that dexamethasone can be used as a chemosensitizer in the adjuvant treatment of
patients with breast cancer.
PMID- 28498439
TI - Knockdown of CREB1 inhibits tumor growth of human gastric cancer in vitro and in
vivo.
AB - cAMP responsive element binding protein 1 (CREB1) gene, has been reported to play
crucial roles in tumor progression and development in various types of cancer.
Little is known, however, about its role and underlying mechanism in gastric
cancer (GC). Herein, we investigated the biological roles and molecular mechanism
of CREB1 in GC. The expression level was determined in four GC cell lines by
quantitative RT-PCR and western blotting. Recombinant expression vector carrying
small interfering RNA (siRNA) targeting CREB1 was constructed and then
transfected into human GC cell line (SGC-7901). Cell proliferation, colony
formation, cycle distribution, migration and invasion in vitro were determined by
MTT, colony forming, flow cytometry, would healing and Transwell invasion assays
after CREB1 knockdown. Tumor growth in vivo was assessed by measurement of tumor
volume and weight in a nude mouse model. We found that CREB1 was highly expressed
in the human GC cell lines. We also showed that knockdown of CREB1 in SGC-7901
cells significantly inhibited cell proliferation, colony formation, migration and
invasion and induced cell arrest at G1/G0 phase in vitro, as well as suppressed
tumor growth in vivo. In addition, CREB1 knockdown was able to significantly
reduce expression of its downstream target genes cyclin D1, Bcl-2 and MMP-9 in
vitro and in vivo. These findings suggest that CREB1 may be a potential
therapeutic target for the treatment of gastric cancer.
PMID- 28498440
TI - Gastrin induces multidrug resistance via the degradation of p27Kip1 in the
gastric carcinoma cell line SGC7901.
AB - Multidrug resistance (MDR) is one of the major reasons for the failure of
chemotherapy-based gastric carcinoma (GC) treatments, hence, biologically based
therapies are urgently needed. Gastrin (GAS), a key gastrointestinal (GI)
hormone, was found to be involved in tumor formation, progression, and
metastasis. In this study, quantitative real-time polymerase chain reaction (qRT
PCR) and immunohistochemical staining analysis revealed a high level of
expression of GAS in drug-insensitive GC tissues (P<0.01) and similar results
were revealed in GC cell lines SGC7901 and its multidrug-resistant variants
SGC7901/VCR and SGC7901/ADR. We constructed a eukaryotic expression vector
pCDNA3.1(+)/GAS for GAS overexpression and recombinant lentiviral vectors for
specific siRNA (siGAS). Transfection of pCDNA3.1(+)/GAS increased (P<0.05) while
transfection of siGAS (P<0.05) and co-treated with paclitaxel (TAX) and
vincristine (VCR) combination (TAX-VCR) decreased (P<0.01) the cell viability of
SGC7901, SGC7901/VCR and SGC7901/ADR. Apoptosis rates of SGC7901/VCR and
SGC7901/ADR were reduced by pCDNA3.1(+)/GAS and increased by siGAS (P<0.05). The
apoptosis rates of SGC7901/VCR, SGC7901/ADR and SGC7901 were all upregulated
(P<0.01) when cells were co-treated with a combination of siGAS and TAX-VCR.
Additionally, siGAS significantly downregulated the expression of Bcl-2 and
multidrug-resistant associate protein (MRP1) and P-glycoprotein (Pgp) (P<0.05) in
SGC7901/VCR and SGC7901/ADR cells. Moreover, GAS overexpression in SGC7901 cells
significantly inhibited p27Kip1 expression but increased phosphorylation levels
of p27Kip1 on Thr (187) and Ser (10) sites (P<0.05), as well as increasing
nuclear accumulation of S-phase kinase-associated protein 2 (Skp2) and
cytoplasmic accumulation of the Kip1 ubiquitination-promoting complex (KPC)
(P<0.05). Silencing of Skp2 blocked the promoting effects of pCDNA3.1(+)/GAS on
viability, the expression of MRP1 and Pgp and the inhibitory effects of
pCDNA3.1(+)/GAS on apoptosis. In conclusion, we suggest that GAS contributes to
the emergence of MDR of SGC7901 cells via the degradation of p27Kip1.
PMID- 28498441
TI - Radiolabeling of VEGF165 with 99mTc to evaluate VEGFR expression in tumor
angiogenesis.
AB - Angiogenesis is the main process responsible for tumor growth and
metastatization. The principal effector of such mechanism is the vascular
endothelial growth factor (VEGF) secreted by cancer cells and other components of
tumor microenvironment. Radiolabeled VEGF analogues may provide a useful tool to
noninvasively image tumor lesions and evaluate the efficacy of anti-angiogenic
drugs that block the VEGFR pathway. Aim of the present study was to radiolabel
the human VEGF165 analogue with 99mTechnetium (99mTc) and to evaluate the
expression of VEGFR in both cancer and endothelial cells in the tumor
microenvironment. 99mTc-VEGF showed in vitro binding to HUVEC cells and in vivo
to xenograft tumors in mice (ARO, K1 and HT29). By comparing in vivo data with
immunohistochemical analysis of excised tumors we found an inverse correlation
between 99mTc-VEGF165 uptake and VEGF histologically detected, but a positive
correlation with VEGF receptor expression (VEGFR1). Results of our studies
indicate that endogenous VEGF production by cancer cells and other cells of tumor
microenvironment should be taken in consideration when performing scintigraphy
with radiolabeled VEGF, because of possible false negative results due to
saturation of VEGFRs.
PMID- 28498442
TI - Prognostic significance of altered miRNA expression in whole blood of OSCC
patients.
AB - Currently, there is a lack of blood markers for the detection of recurrent oral
squamous cell carcinoma (OSCC). The present study aimed to investigate whether
the aberrant expression of single microRNAs (miRNAs) in whole blood of patients
could serve as a biomarker for persistent or recurrent OSCC. Whole blood of 2
groups of formerly treated OSCC patients was investigated by RT-qPCR for their
circulating miRNA profiles. The R-OC group included patients with recurrence of
OSCC (n=21) and the NR-OC group included patients without recurrence (n=21). Fold
changes and significance of the differences in miRNA expression levels between
the groups were determined. A cut-off point (COP) for the discrimination between
the R-OC and NR-OC groups was calculated and the significance between over/under
expression of the miRNAs and the recurrence of malignancy was determined.
Significant differences in the miRNA expression in whole blood of the R-OC and NR
OC groups were found. The levels of miR-3651 and miR-494 were significantly
increased and the level of miR-186 was significantly decreased in whole blood of
the R-OC patients (pmiR-3651=0.001, pmiR-494=0.003 and pmiR-186=0.001). By the
determination of the COP, increased or decreased expression of the markers was
significantly correlated to the recurrence of the disease. Altered expression of
miR-494, miR-3651 and miR-186 appears to be associated with the recurrence of
OSCC. The present study may form the basis for establishing a blood test as a
minimally invasive method for the detection of the recurrence of OSCC.
PMID- 28498443
TI - Silencing of both ATF4 and PERK inhibits cell cycle progression and promotes the
apoptosis of differentiating chondrocytes.
AB - In the current study, we demonstrate that the silencing of protein kinase R (PKR)
like endoplasmic reticulum (ER) kinase (PERK) and activating transcription factor
6 (ATF4) (using small interfering RNA expression constructs) inhibits the
chondrocyte cell cycle and proliferation in vitro and ex vivo. The silencing of
PERK alone using siRNA against PERK (siPERK) led to arrest in the G1 phase, it
decreased the number of cells in the S phase, and delayed progressoin to the G2-M
phase. Co-transfection with siRNA against ATF (siATF4) led to a more profound
inhibitory effect on cell cycle progression. Moreover, transfection with siPERK
was associated with enhanced endoplasmic reticulum (ER) stress-induced apoptosis
during bone morphogenetic protein 2 (BMP2)-induced chondrogenesis, and
transfection with siATF4 exacerbated ER stress-related cell death. Data from flow
cytometry (FCM), immunohistochemistry and TUNEL assays supported these findings
in vitro and ex vivo. As shown by our results, the combined effect of the
silencing of ATF4 and PERK led to the activation of an ER stress-specific caspase
cascade in the cartilage tissue. On the whole, these findings reveal a new
crucial combined effect of the silencing of PERK and ATF4 in modulating ER stress
mediated apoptosis during chondrocyte differentiation and proliferation.
PMID- 28498444
TI - High expression of PFTK1 in cancer cells predicts poor prognosis in colorectal
cancer.
AB - The serine/threonine-protein kinase PFTAIRE 1 (PFTK1) is a member of the cyclin
dependent kinase family that is highly expressed in several malignant tumors,
including hepatocellular carcinoma, esophageal, breast and gastric cancers, and
glioma. It contributes to tumor progression and influences tumor prognosis.
However, the expression and clinicopathological significance of PFTK1 in human
colorectal cancer (CRC) remain to be elucidated. The present study aimed to
examine the expression of PFTK1 and to evaluate the clinical significance of its
expression in human CRC. Reverse transcription-quantitative polymerase chain
reaction was performed on 10 fresh CRC and 10 surrounding normal tissue samples
to detect and compare the expression of PFTK1 mRNA in CRC and normal colorectal
tissues. Immunohistochemistry was performed on 179 CRC tissue specimens and 47
control samples of normal colorectal lesions to characterize the expression of
PFTK1 protein. Kaplan-Meier overall survival (OS) rate and Cox regression
analyses were performed to evaluate the prognosis of patients with CRC. The
expression of PFTK1 mRNA in CRC tissues (1.433+/-0.168) was significantly higher
compared with normal tissues (0.853+/-0.107; t=1.97 ('t' was the value obtained
from quantification of the mRNA data, following a paired t-test), P=0.008). High
PFTK1 expression in cancerous cells was detected in 92 of the CRC specimens
(51.40%), and high levels of PFTK1 were associated with tumor node metastasis
(TNM) stage (P=0.042), tumor classification (P=0.022) and preoperative
carcinoembryonic antigen (CEA) level (P<0.001). Kaplan-Meier OS rate and Cox
regression analysis revealed that high PFTK1 expression level (hazard ratio
(HR)=1.999; P=0.019) was an independent prognostic factor of CRC patients. The
degree of differentiation (HR, 0.368, P=0.003), TNM classification (HR, 2.118,
P=0.001) and preoperative CEA level (HR, 2.302, P=0.003) were also predictors of
the prognosis of patients with CRC. The present study suggested that PFTK1 may be
a potential anticancer target and prognostic marker in patients with CRC.
PMID- 28498445
TI - Evaluation of expression of cancer stem cell markers and fusion gene in synovial
sarcoma: Insights into histogenesis and pathogenesis.
AB - Synovial sarcoma (SS) is an aggressive soft tissue tumor, with uncertain
histological and cellular origin. SYT-SSX is considered to be responsible for
sarcoma initiation and progression. The histogenesis and pathogenesis of this
tumor are poorly understood, and prognosis of patients of SS is unsatisfactory.
Recent studies have shown an association of cancer stem cells with the initiation
and development of tumors. We explored immunohistochemical expression level of
stem cell associated markers to determine the possible histogenesis and
pathogenesis of SS. Fusion gene SYT-SSX was tested to assess diagnostic value and
the molecular pathological features. We obtained the clinicopathological data of
20 SS patients, immunohistochemical staining were used to evaluate stem cell
associated markers included CD133, CD29, CD44, nestin, and ALDH1. Fusion gene SYT
SSX was tested by reverse transcriptase-polymerase chain reaction (RT-PCR).
Twenty SS cases were observed and the positive immuno-expression results showed
CD133 (17/20), CD29 (11/20), CD44 (11/20), nestin (6/20), and ALDH1 (5/20).
Fusion gene SYT-SSX was successfully detected by RT-PCR from 18 available
samples. The expression of stem cell-associated markers (CD133, CD29, CD44,
Nestin, and ALDH1) and clinical data (age, gender, sites, tumor size,
histological type, tumor stage, and distant metastases) did not show
statistically significant relationship (P>0.05), whereas, statistically
significance between ALDH1 and metastases was observed (P<0.01). The ALDH1
positive synovial sarcoma (ALDH1+ SS) cases had significantly poor prognosis
compared to ALDH1 negative synovial sarcoma (ALDH1- SS) cases (P<0.05).
Immunohistochemical results indicated different expression levels of the five
cancer stem cell markers in SS suggesting that SS may arise from cancer stem
cells. Fusion gene SYT-SSX may play a critical role in the molecular pathological
of SS.
PMID- 28498446
TI - Synergistic protective effect of FTY720 and vitamin E against simulated cerebral
ischemia in vitro.
AB - The purpose of the present study was to explore the combination effect of FTY720
and vitamin E on cerebral ischemia. Astrocytes were isolated from newborn Sprague
Dawley rats and were subjected to FTY720, vitamin E, or combination of the two.
The astrocyte cultures were then exposed to oxygen-glucose deprivation (OGD) to
simulate an ischemic model in vitro. Cell viability, lactate dehydrogenase (LDH)
leakage and cell apoptosis were detected following 12 h of exposure to OGD. In
addition, the levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL
1beta, total antioxidant capacity, intercellular adhesion molecule (ICAM)-1,
vascular cell adhesion molecule (VCAM)-1, chemokine (C-X-C motif) ligand (CXCL)
10, heme oxygenase (HO)-1 and superoxide dismutase (SOD)-1 were measured. Pre
treatment with FTY720 or vitamin E significantly elevated the cell viability and
decreased LDH release and number of apoptotic cells. Combination treatment with
FTY720 and vitamin E demonstrated a synergistic protective effect on OGD-induced
cell viability, toxicity and apoptosis. Pre-treatment with FTY720 markedly
reduced the release of IL-1beta, TNF-alpha, IL-6, ICAM-1, VCAM-1 and CXCL-10, and
pre-treatment with vitamin E increased the levels of antioxidant, HO-1 and SOD-1.
However, pre-treatment with FTY720 combined with vitamin E revealed a synergistic
effect. Pre-treatment with FTY720 combined with vitamin E exerts synergistic
neuroprotective effects in the simulated cerebral ischemia in vitro.
PMID- 28498447
TI - DEC2 expression antagonizes cisplatin-induced apoptosis in human esophageal
squamous cell carcinoma.
AB - Differentiated embryonic chondrocyte expressed gene 1 (DEC1) and differentiated
embryonic chondrocyte expressed gene 2 (DEC2) belong to the Hairy/Enhancer of
Split subfamily of basic helix-loop-helix factors. Previous studies have
demonstrated that DEC proteins are involved in the regulation of circadian
rhythms, response to hypoxia, and tumorigenesis. However, the roles of DEC1 and
DEC2 in apoptosis of esophageal carcinoma remain unclear. In the present study,
alterations in expression of apoptosis-related markers in human esophageal
squamous cell carcinoma TE-11 cells treated with cisplatin were examined by
western blot, while overall cell viability and apoptosis were analyzed by MTS
assay and hematoxylin and eosin staining, respectively. Following cisplatin
treatment, expression of DEC2 was downregulated, whereas expression of DEC1 was
upregulated. DEC2 overexpression during cisplatin treatment markedly inhibited
expression of the pro-apoptotic factor Bim and slightly increased the anti
apoptotic factor Bcl-xL. However, overexpression of DEC1 during cisplatin
treatment failed to affect expression of these markers. Additionally,
overexpression of DEC2 improved cell viability and decreased cell apoptosis
induced by cisplatin. These results suggested that DEC2 exhibits anti-apoptotic
effects in TE-11 esophageal squamous cell carcinoma cells. Inhibiting DEC2 may
therefore have therapeutic potential for the treatment of esophageal cancer, in
combination with cisplatin.
PMID- 28498448
TI - Sanguinarine protects against ovariectomy-induced osteoporosis in mice.
AB - Natural compounds are alternative agents that have therapeutic potential for
preventing and treating osteoporosis. Traditionally, sanguinarine has been used
clinically due to its diverse biological properties, including antimicrobial,
anti-inflammatory and anticancer effects. Recently, for the first time, it was
reported that sanguinarine inhibits osteoclast differentiation and bone
resorption by suppressing the tumor necrosis factor ligand superfamily member 11
induced nuclear factor-kappaB and extracellular signal-regulated kinase signaling
pathways in vitro. Therefore, the present study further investigated the
pharmacological effect of sanguinarine on osteoporosis in vivo. Micro-computed
tomography and histomorphometry analysis demonstrated that sanguinarine, at low
and high concentrations, prevents ovariectomy (OVX)-induced bone loss. In
addition, further investigation of the cellular response in vivo revealed that
sanguinarine inhibited osteoclastic bone resorption and promoted osteoblastic
bone formation in a dose-dependent manner. Therefore, the present study
demonstrated that sanguinarine protected mice from OVX-induced osteoporosis by
modulating bone remodeling, indicating that sanguinarine may have potential in
the treatment of osteoporosis.
PMID- 28498450
TI - [Corrigendum] miR-28-5p promotes the development and progression of ovarian
cancer through inhibition of N4BP1.
AB - Following the publication of this article, the authors noted that there was an
error in the affiliations. Specifically, the affiliation of the first author JUAN
XU should be: Jinhua Municipal Central Hospital, Jinhua Hospital of Zhejiang
University, Jinhua, Zhejiang 321000, P.R. China. [the original article was
published in the International Journal of Oncology 50: 1383-1391, 2017; DOI:
10.3892/ijo.2017.3915].
PMID- 28498449
TI - Bioinformatic analysis of the effects and mechanisms of decitabine and cytarabine
on acute myeloid leukemia.
AB - Acute myeloid leukemia (AML) is a frequently occurring malignant disease of the
blood and may result from a variety of genetic disorders. The present study aimed
to identify the underlying mechanisms associated with the therapeutic effects of
decitabine and cytarabine on AML, using microarray analysis. The microarray
datasets GSE40442 and GSE40870 were downloaded from the Gene Expression Omnibus
database. Differentially expressed genes (DEGs) and differentially methylated
sites were identified in AML cells treated with decitabine compared with those
treated with cytarabine via the Linear Models for Microarray Data package,
following data pre-processing. Gene Ontology (GO) analysis of DEGs was performed
using the Database for Annotation, Visualization and Integrated Analysis
Discovery. Genes corresponding to the differentially methylated sites were
obtained using the annotation package of the methylation microarray platform. The
overlapping genes were identified, which exhibited the opposite variation trend
between gene expression and DNA methylation. Important transcription factor (TF)
gene pairs were screened out, and a regulated network subsequently constructed. A
total of 190 DEGs and 540 differentially methylated sites were identified in AML
cells treated with decitabine compared with those treated with cytarabine. A
total of 36 GO terms of DEGs were enriched, including nucleosomes, protein-DNA
complexes and the nucleosome assembly. The 540 differentially methylated sites
were located on 240 genes, including the acid-repeat containing protein (ACRC)
gene that was additionally differentially expressed. In addition, 60 TF pairs and
overlapped methylated sites, and 140 TF-pairs and DEGs were screened out. The
regulated network included 68 nodes and 140 TF-gene pairs. The present study
identified various genes including ACRC and proliferating cell nuclear antigen,
in addition to various TFs, including TATA-box binding protein associated factor
1 and CCCTC-binding factor, which may be potential therapeutic targets of AML.
PMID- 28498451
TI - Differential effects of p38 and Erk1/2 on the chondrogenic and osteogenic
differentiation of dental pulp stem cells.
AB - The extracellular signal-regulated protein kinase 1/2 (Erk1/2) and p38 mitogen
activated protein-kinase pathways serve important roles in the regulation of
osteogenic and chondrogenic differentiation in mesenchymal stem cells (MSCs).
However, the exact mechanism remains unclear, and the effect is controversial. In
the present study, the effects of Erk1/2 and p38 on the osteogenic and
chondrogenic differentiation of dental pulp stem cells (DPSCs) were compared in
vitro. The results indicated that inhibition of Erk1/2 is able to enhance the
osteogenic differentiation of DPSCs and inhibit chondrogenic differentiation,
whereas inhibition of p38 demonstrated the opposite effect. When compared with
previous studies, the present study further confirmed that Erk1/2 and p38 serve
important, but complicated, roles in regulating the differentiation of MSCs.
Different chemical and physical stimuli, cell types, culture methods, times of
inhibitor administration and the dosage of the inhibitor may influence the effect
of Erk1/2 and p38 on the differentiation of MSCs. The present study aims to
better understand the mechanisms that control the differentiation of MSCs and may
be helpful in creating more effective tissue regeneration.
PMID- 28498452
TI - Calpain and AR-V7: Two potential therapeutic targets to overcome acquired
docetaxel resistance in castration-resistant prostate cancer cells.
AB - Docetaxel-based chemotherapy has been widely used as the first-line treatment for
castration-resistant prostate cancer (CRPC) patients. However, the mechanisms of
docetaxel-resistance remain unclear. In the present study with the establishment
of 2 in vitro models of docetaxel-resistant CRPC cell sublines, we firstly
reported that activation of calpain may play a promotional role in the resistance
of docetaxel in prostate cancer, meanwhile using the calpain inhibitor combined
with docetaxel improved the efficiency of docetaxel in docetaxel-resistant cell
sublines. Moreover, we also found that the expression of androgen-independent
constitutively and transcriptionally active androgen receptor splice variant-7
(AR-V7) remained high in the docetaxel-resistant CRPC cell subline Rv1-DR, and
that it may be involved in acquired docetaxel-resistance of CRPC. However, a
novel importin-beta inhibitor (importazole) was only capable of slightly
decreasing the transcriptional activity of the AR signaling pathway via blocking
nuclear import of AR-FL and various non-specific AR-Vs, instead of AR-V7. These
findings suggest that calpain and AR-V7 may serve as important biomarkers in the
treatment of CRPC, and targeting calpain and AR-V7 may provide a new approach in
overcoming docetaxel-resistance.
PMID- 28498453
TI - The inhibition of microRNA-15a suppresses hepatitis B virus-associated liver
cancer cell growth through the Smad/TGF-beta pathway.
AB - In the present study, the role of microRNA-15a (miR-15a) was investigated in
hepatitis B virus (HBV)-associated liver cancer. The results revealed that the
expression levels of miR-15a were increased in HBV-associated liver cancer
tissues compared with the levels in normal tumor-adjacent tissues. Moreover, Smad
7 protein expression in patients with HBV-associated liver cancer was higher than
that in normal tumor-adjacent tissues. In addition, miR-15a expression and Smad-7
protein expression were increased in HepG2 hepatocellular carcinoma cells
compared with that noted in L-02 normal hepatocytes. In HepG2 cells, miR-15a
inhibition suppressed cell proliferation and increased Smad-7 protein expression.
The inhibition of miR-15a was also demonstrated to decrease transforming growth
factor (TGF)-beta1 protein expression and Smad-2, p-Smad-2 and Smad-4 expression
levels in HepG2 cells. Furthermore, FSP1 protein expression and caspase-3/-7
activities were enhanced by miR-15a inhibition in HepG2 cells compared with the
control group. Treatment with recombinant TGF-beta1 was demonstrated to activate
Smad-2/-4 and FSP1 protein expression and increase caspase-3/-7 activity in HepG2
cells. Collectively, these findings demonstrate that the miR-15a/Smad-7/TGF-beta
pathway is important in HBV-associated liver cancer.
PMID- 28498454
TI - Identification of SETD2-NF1 fusion gene in a pediatric spindle cell tumor with
the chromosomal translocation t(3;17)(p21;q12).
AB - Spindle cell tumors are clinically heterogeneous but morphologically similar
neoplasms. The term refers to the tumor cells' long and slender microscopic
appearance. Distinct subgroups of spindle cell tumors are characterized by
chromosomal translocations and also fusion genes. Other spindle cell tumors exist
that have not yet been found to have characteristic, let alone pathognomonic,
genetic or pathogenetic features. Continuous examination of spindle cell tumors
is likely to reveal other subgroups that may, in the future, be seen to
correspond to meaningful clinical differences and may even be therapeutically
decisive. We analyzed genetically a pediatric spindle cell tumor. Karyotyping
showed the tumor cells to carry a t(3;17)(p21;q12) chromosomal translocation
whereas RNA sequencing identified a SETD2-NF1 fusion gene caused by the
translocation. RT-PCR together with Sanger sequencing verified the presence of
the above-mentioned fusion transcript. Interphase FISH analysis confirmed the
existence of the chimeric gene and showed that there was no reciprocal fusion.
The fusion transcript codes for a protein in which the last 114 amino acids of
SETD2, i.e., the entire Set2 Rpb1 interacting (SRI) domain of SETD2, are replaced
by 30 amino acids encoded by the NF1 sequence. The result would be similar to
that seen with truncating SETD2 mutations in leukemias. Absence of the SRI domain
would result in inability to recruit SETD2 to its target gene locus through
binding to the phosphor-C-terminal repeat domain of elongating RNA polymerase II
and may affect H3K36 methylation. Alternatively, loss of one of two functional
SETD2 alleles might be the crucial tumorigenic factor.
PMID- 28498455
TI - Overexpression of MAGEA2 has a prognostic significance and is a potential
therapeutic target for patients with lung cancer.
AB - Melanoma-associated antigens (MAGE) are expressed in different type of cancers
including lung cancer and have been shown to be functionally related to p53 tumor
suppressor gene. Little is known about the relationship between MAGE genes and
p53 aberrant expression in lung cancer. The aims of this study were to observe
the expression of MAGEA2, examine the role of MAGEA2 in lung cancer survival,
investigate its correlation between MAGEA2 and p53, and explore its
clinicopathologic significance as a prognostic marker. Quantitative reverse
transcription-polymerase chain reaction was performed to detect the expression of
MAGEA2 using 36 primary tumors and 31 metastatic lymph nodes from patients with
lung cancer. The role of MAGEA2 in cancer cell growth and in the regulation of
p53 downstream genes were examined using small interfering RNA. The expression of
MAGEA2 and p53 were analyzed immunohistochemically using tissue microarray from
353 resected lung specimens. High-level expression of MAGEA2 (High-MAGEA2) was
confirmed in lung tumors with high frequency. Inhibiting MAGEA2 expression
effectively suppressed cancer cell growth and decreased the expression of p53
downstream target genes in vitro. In adenocarcinoma, High-MAGEA2 was strongly
associated with aberrant p53 expression (P<0.001) and was associated with worse
clinical outcomes (5-year OS, 87.1% in low vs. 74.1% in high, P=0.014). Aberrant
p53 expression was also significant worse prognostic factor (P=0.029). Among the
adenocarcinoma patients with wild-type p53, High-MAGEA2 had poorer prognosis than
low-level MAGEA2 groups (5-year OS, 90.1% vs. 72.1%, P=0.037), whereas had no
difference in p53 aberrant tumors. On multivariate analysis, MAGEA2 was
independently associated with survival (hazard ratio; 2.12, P=0.030). In
conclusion, suppression of MAGEA2 in lung cancer cells significantly reduced the
growth/survival of cancer cells. High-MAGEA2 was identified as an independent
prognostic factor in lung adenocarcinoma. Specific inhibition of MAGEA2 may be a
promising therapeutic strategy for patients with lung cancer.
PMID- 28498456
TI - miR-944 inhibits cell migration and invasion by targeting MACC1 in colorectal
cancer.
AB - Dysfunction of microRNAs (miRNAs) is strongly proved to participate in the
pathogenesis and tumorigenicity of colorectal cancer (CRC). miR-944 was reported
to play either oncogenic or tumor suppressive roles in human cancers. A recent
study reported that the levels of miR-944 in recurrent CRC patients were
evidently lower than that in non-recurrent cases, suggesting that miR-944 may
function as a tumor suppressive miRNA in CRC. Yet, the clinical value and
biological function of miR-944 remain rarely known in CRC. In the present study,
we present that miR-944 level in CRC tissues is notably reduced compared to
matched non-cancerous specimens. Its decreased level is evidently correlated with
malignant clinical parameters and poor prognosis of CRC patients. Accordingly,
the levels of miR-944 were obviously downregulated in CRC cells. Ectopic
expression of miR-944 in CRC cells prominently inhibits the migration and
invasion of tumor cells, while miR-944 knockdown increased these effects of CRC
cells. Mechanically, miR-944 negatively regulated the metastasis-associated in
colon cancer-1 (MACC1) abundance in CRC cells. Herein, MACC1 was found to be a
downstream molecule of miR-944 in CRC. An inversely correlation between miR-944
and MACC1 was confirmed in CRC specimens. Furthermore, restoration of MACC1
expression could abrogate the anti-metastatic effects of miR-944 on CRC cells
with enhanced cell migration and invasion. MACC1/Met/AKT signaling may be
implicated with the function of miR-944 in CRC cells. Altogether, miR-944
potentially act as a prognostic predictor and a drug-target for CRC patients.
PMID- 28498457
TI - SUVmax of 18F-FDG PET/CT correlates to expression of major chemotherapy-related
tumor markers and serum tumor markers in gastric adenocarcinoma patients.
AB - The expression of P53 was previously found by us significantly correlated with
maximal standardized uptake value (SUVmax) in non-small cell lung cancer (NSCLC)
patients. Hence, the aim of this study was to clarify the relationship between
SUVmax and the status of the chemotherapy-related tumor marker expression or
serum tumor markers in gastric adenocarcinoma patients. Sixty-four gastric
adenocarcinoma patients who underwent 18F-FDG PET/CT prior to treatment were
enrolled in this study. Immunohistochemistry was performed to detect changes of
Her-2, P53 and Survivin in lesions, and electrochemiluminescence (ECL) method was
used to quantify expression of serum CA72-4, CA19-9 and CEA of these patients.
Then, the relationships between these parameters above were assessed by Spearman
correlation analysis. Also, receiver-operating characteristic (ROC) curve was
performed to determine the best cut-off value of SUVmax for suggesting
chemotherapy resistant tumor markers. Besides, we identified a linear correlation
to estimate the equations between SUVmax and the serum tumor markers. Our results
showed that higher SUVmax was detected in patients with positive expression of
Her-2 and P53, compared with negative groups. The Spearman correlation analysis
showed that SUVmax was associated with Her-2 or P53 with the moderate relevant
Pearson correlation coefficient. ROC curve analysis showed that the sensitivity
and specificity of SUVmax for suggesting Her-2 or P53-positive, when the cut-off
value of SUVmax was set at 3.25 or 5.45, respectively. Moreover, the relationship
between SUVmax and serum tumor markers were analyzed by linear correlation
analysis, and serum CA72-4 and CA19-9 could be used as independent parameters to
establish an equation for SUVmax by the linear regression models. These results
suggested that SUVmax of 18F-FDG PET/CT could be used to predict and evaluate Her
2 or P53 related chemotherapy resistance of gastric adenocarcinoma patients.
However, before PET/CT scanning, serum tumor markers could be used to calculate
the SUVmax approximately.
PMID- 28498458
TI - Chloroform fraction of Scutellaria barbata D. Don inhibits the growth of
colorectal cancer cells by activating miR-34a.
AB - Scutellaria barbata D. Don (SB) is a well known formula in traditional Chinese
medicine, which exhibits potent anticancer effects on various cancers. Many
miRNAs play crucial roles in the regulation of cancer, for instance, miR-34a
functions as a tumor suppressor, and is often downregulated during cancer. In
this study, we investigated the role of ECSB in suppressing the growth of human
colon cancer HCT-8 cells, and whether this is mediated by regulation of miR-34a
and its downstream target genes, using real-time PCR and western blot analysis.
ECSB treatment significantly inhibited the proliferation of HCT-8 cells and
promoted apoptosis in a dose-dependent manner. In addition, ECSB treatment
significantly increased the level of miR-34a expression and decreased the levels
of Bcl-2, Notch1/2 and Jagged1 expression. Furthermore, knockdown of miR-34a
expression through transfection of anti-miR-34a oligonucleotide was significantly
reversed by ECSB treatment. Likewise, knockdown of miR-34a resulted in
significant upregulation of Bcl-2, Notch1/2 and Jagged1 expression, which was
reversed following ECSB treatment. Therefore, this study reveals that ECSB
inhibited cancer cell growth via promoting apoptosis and inhibiting
proliferation, through regulation of miR-34a. These findings further support the
use of ECSB as an effective therapeutic agent against colon cancer.
PMID- 28498459
TI - Inhibitors of PARP-1 exert inhibitory effects on the biological characteristics
of hepatocellular carcinoma cells in vitro.
AB - It has been confirmed that the inhibitors of poly ADP-ribose polymerF(^9ase-1
(PARP-1) can inhibit the proliferation, apoptosis and invasion of tumor cells.
However, the effects of inhibitors of PARP-1 on hepatocellular carcinoma remain
to be elucidated. The aim of the present study was to investigate the effect of
three types of PARP-1 inhibitor on the proliferation, apoptosis and migration of
hepatocellular carcinoma in vitro. An MTT assay was performed to detect the
proliferation of HepG2 cells following treatment with the PARP-1 inhibitors,
AG014699, BSI-201 and AZD-2281. Flow cytometry was used to detect the apoptosis
of HepG2 cells, Western blot analysis was used to detect the protein expression
of Casepase-3, Casepase-8, B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax),
Bcl-2, phosphatase and tensin homolog (PTEN), tissue inhibitor of
metalloproteinase (TIMP) 3 and matrix metalloprotease (MMP) 3. A Transwell assay
was performed to detect the migration of HepG2 cells. The results showed that
AG014699, BSI-201 and AZD-2281 had an inhibitory effect on the proliferation of
HepG2 cells in a time- and concentration-dependent manner. AG014699 at
concentrations of 10, 30 and 50 umol/l, and BSI-201 at concentrations of 20, 40
and 60 umol/l induced the apoptosis of HepG2 cells, and the apoptotic rates were
particularly high at 48 h (31, vs. 0.01%; P<0.01 and 24.12, vs. 0.03%,
respectively; P<0.01). The protein expression levels of Caspase 3, Caspase 8,
Bax, PTEN and TIMP 3 increased with increasing drug concentrations, whereas the
protein levels of Bcl-2 and MMP3 decreased with increasing drug concentrations,
and were significantly different compared with those in the control group
(P<0.01). In conclusion, AG014699, BSI-201 and AZD-2281 inhibitors of PARP-1
significantly inhibited the proliferation of HepG2 cells, however, AG014699 and
BSI-201 demonstrated more sensitivity, induced apoptosis and inhibited migration
of the hepatocellular carcinoma cells, which may be associated with alterations
of the apoptosis signaling pathway and the expression of proteins associated with
migration.
PMID- 28498460
TI - MCM7 amplification and overexpression promote cell proliferation, colony
formation and migration in esophageal squamous cell carcinoma by activating the
AKT1/mTOR signaling pathway.
AB - The roles and mechanisms of mini-chromosome maintenance complex component 7
(MCM7) amplification and overexpression in esophageal carcinogenesis were
investigated. By analyzing the TCGA datasets, we found that MCM7 was amplified in
approximately 12% of esophageal squamous cell carcinomas (ESCCs), and in more
than 4% of head and neck squamous cell carcinomas and stomach carcinomas.
Overexpression of MCM7 was further verified in three independent GEO datasets of
esophageal cancer. Knockdown of MCM7 using two siRNAs significantly inhibited
cell proliferation, colony formation and migration of KYSE510 and EC9706 cells in
vitro. Noteworthy, we further found that silencing of MCM7 suppressed the
phosphorylation of AKT1 and mTOR both in KYSE510 and EC9706 cells, and reduced
the cell cycle regulatory proteins cyclin D1, cyclin E2 and CDK2. Taken together,
our findings suggested that MCM7 promoted tumor cell proliferation, colony
formation and migration of ESCC cells via activating AKT1/mTOR signaling pathway.
PMID- 28498461
TI - Increased production of human fibroblast growth factor 17 in Escherichia coli and
proliferative activity in NIH3T3 cells.
AB - Fibroblast growth factor 17 (FGF17) is a novel member of the FGFs family, which
is essential for cell development, tissue repair, tumor growth and invasion. The
aim of the current study was to obtain a high expression level of recombinant
human FGF17 (rhFGF17), including soluble proteins and inclusion bodies. An
optimized rhFGF17 cDNA sequence was cloned into a pET3a vector, then the pET3a
hFGF17 vector was transformed into BL21(DE3)pLysS Escherichia coli cells.
Expression was induced by optimizing the conditions using isopropyl beta-D-1
thiogalactopyranoside (IPTG) and it was confirmed that a 24-h exposure to 0.8 mM
IPTG at 16C provided the optimal condition for soluble hFGF17. Furthermore, for
the inclusion bodies, the optimal condition was a 4-h exposure to 0.4 mM IPTG at
37C. Two forms of rhFGF17 protein were purified by heparin affinity and SP
Sepharose Fast Flow chromatography. MTT assays demonstrated that the purified
rhFGF17 exerted an important effect on the proliferative activity of NIH3T3
cells, although there was no significant difference when compared with standard
rhFGF17. Thus, an optimal and economic expression system was created in the
present study for rhFGF17 in E. coli. This expression strategy enables the
preparation of sufficient and highly bioactive rhFGF17 for further investigation
of underlying mechanisms.
PMID- 28498462
TI - Loss of Reelin suppresses cell survival and mobility in non-Hodgkin lymphoma.
AB - Reelin, a secreted glycoprotein, was recently demonstrated to be involved in the
pathogenesis of cancer. However, its oncogenic activities in non-Hodgkin lymphoma
(NHL) remain unclear. Therefore, we aimed to evaluate the functional role of
reelin in NHL, and the underlying molecular mechanisms. In the present study, we
analyzed reelin expression in lymphoma tissues and cell lines using
immunohistochemistry, immunofluorescence staining, qRT-PCR and western blotting.
Then, the expression of Reelin was silenced with short hairpin RNA (shRNA)
expressing plasmid in the NHL cell line A20. The effects of Reelin depletion on
cell growth, migration and invasion in vitro were determined by CCK-8 and
transwell assays. Flow cytometry was used to examine the cell cycle status and
cellular apoptosis. Hoechst 33258 fluorescence staining was used to analyze
morphologic changes caused by apoptosis. The second messenger, cAMP was analyzed
by ELISA. In addition, we used nude mice to evaluate the tumorigenic ability of
reelin. Aberrant upregulated levels of mRNA and protein of reelin were observed
in lymphoma tissues and cell lines. Knockdown of reelin suppressed lymphoma
growth, migration and invasion ability of A20. Furthermore, reelin depletion
induced cell cycle arrest in G0/G1 phase and promoted apoptosis of A20 cells.
Further analysis indicated that knockdown of reelin downregulated the expression
of CDK5 and IL-10 and activated caspase-3 in shReelin group. ELISA assay showed
cAMP at a lower level in shReelin group. SQ22536, a cAMP pathway inhibitor,
treated A20 cells and revealed likely effects. The tumor size in a mouse model
injected shReelin was significantly smaller than controls. There results suggest
that reelin played essential roles in the development of lymphoma and might be a
potential drug target in lymphoma.
PMID- 28498463
TI - miR-138 suppresses the proliferation, metastasis and autophagy of non-small cell
lung cancer by targeting Sirt1.
AB - The present study determined the role and mechanism of miR-138 in non-small cell
lung cancer (NSCLC). In total, 45 freshly resected clinical NSCLC tissues were
collected. The expression of miR-138 in tissues and cell lines were determined by
real-time quantitative PCR. miR-138 mimics were transfected into A549 and Calu-3
cells in vitro, and then the effects of miR-138 on lung cancer cell
proliferation, cell cycle, invasion and metastasis were investigated by CCK-8
assay, Transwell and flow cytometry, respectively. The protein expression of the
potential target gene Sirt1 in lung cancer cells were determined by western blot
analysis. Dual-luciferase reporter assay was performed to further confirm whether
Sirt1 was the target gene of miR-138. The expression of miR-138 was significantly
lower in lung cancer tissues and was negatively correlated to the differentiation
degree and lymph node metastasis of lung cancer. In vitro experiment results
showed that miR-138 inhibited lung cancer cell proliferation, invasion and
migration. It was verified that miR-138 could downregulate Sirt1 protein
expression, inhibit epithelial-mesenchymal transition (EMT), decrease the
activity of AMPK signaling pathway and elevate mTOR phosphorylation level. Dual
luciferase reporter assay demonstrated that miR-138 could directly regulate
Sirt1. Downregulation of Sirt1 alone can also cause the same molecular and
biological function changes. Western blot analysis and confocal microscopy
results indicated that overexpression of miR-138 or interference of Sirt1
expression could inhibit lung cancer cell autophagy activity possibly through
AMPK-mTOR signaling pathway. miR-138 plays a tumor suppressor function in lung
cancer. It may inhibit the proliferation, invasion and migration of lung cancer
through downregulation of Sirt1 expression and activation of cell autophagy. The
downregulation of miR-138 is closely related to the development of lung cancer.
PMID- 28498464
TI - Proinflammatory effects of S100A8/A9 via TLR4 and RAGE signaling pathways in BV-2
microglial cells.
AB - S100A8/A9, a heterodimer of the two calcium-binding proteins S100A8 and S100A9,
has emerged as an important proinflammatory mediator in acute and chronic
inflammation. However, whether S100A8/A9 is implicated in microglial-induced
neuroinflammatory response remains unclear. Here, we found that S100A8/A9
significantly increased the secretion of proinflammatory cytokines inclu-ding
tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in cultured BV-2
microglial cells. Inhibition of the Toll-like receptor 4 (TLR4) and the receptor
for advanced glycation end-products (RAGE) with C225 and a RAGE-blocking
antibody, respectively significantly reduced the secretion of TNF-alpha and IL-6
from S100A8/A9-stimulated BV-2 microglial cells. Furthermore, S100A8/A9 markedly
enhanced the nuclear translocation of NF-kappaB p65 and the DNA-binding
activities of NF-kappaB in BV-2 microglial cells, and suppression of ERK and
JNK/MAPK signaling pathways by PD98059 or SP600125 significantly inhibited NF
kappaB activity and the release of TNF-alpha and IL-6 in the S100A8/A9-treated BV
2 microglial cells. Our data also showed that inhibition of NF-kappaB with
pyrrolidine dithiocarbamate (PDTC) significantly reduced the secretion of TNF
alpha and IL-6 from BV-2 microglial cells treated with S100A8/A9. Taken together,
our data suggest that S100A8/A9 acts directly on BV-2 microglial cells via
binding to TLR4 and RAGE on the membrane and then stimulates the secretion of
proinflammatory cytokines through ERK and JNK-mediated NF-kappaB activity in BV-2
microglial cells. Targeting S100A8/A9 may provide a novel therapeutic strategy in
microglial-induced neuroinflammatory diseases.
PMID- 28498465
TI - Identification of a novel hypertrophic cardiomyopathy-associated mutation using
targeted next-generation sequencing.
AB - Hypertrophic cardiomyopathy (HCM), one of the most common forms of myocardial
diseases, is the major cause of sudden cardiac death in young adults and
competitive athletes. Analyses of gene mutations associated with HCM are valuable
for its molecular diagnosis, genetic counseling, and management of familial HCM.
To dissect the relationship between the clinical presentation and gene mutations
of HCM, the genetic characterizations of 19 HCM-related genes in 18 patients (8
cases from 6 pedigrees with familial HCM and 10 cases without familial HCM) were
detected using next-generation sequencing (NGS). As a result, 12 disease-related
mutations were identified in the 18 subjects, including 6 single mutations and 3
double mutations [MYBPC3 (p.Gln998Glu) plus TNNI3 (p.Arg145Gly), PRKAG2
(p.Gly100Ser) plus MYBPC3 (p.Lys1209Serfs*28) and TNNI3 (p.Glu124Gln) plus GLA
(p.Trp47*)]. The 3 heterozygous double mutations were discovered for the first
time in the malignant familial HCM patients. Of the 6 single mutations, a novel
mutation was found in tafazzin (TAZ, p.Ile208Val), and a mutation in beta-myosin
heavy chain gene (MYH7, p.Arg54Gln), which was reported as rare in the general
population, was firstly found in one HCM patient. Identification of novel and
rare mutations in HCM patients have added new data to the spectrum of gene
mutations associated with this disease. These findings provide an essential basis
for the molecular diagnosis and better management of family members at risk of
familial HCM.
PMID- 28498466
TI - Elevated SLC26A4 gene promoter methylation is associated with the risk of
presbycusis in men.
AB - Presbycusis affects approximately one-third of people over the age of 65 and is a
worldwide health problem. In the current study, whether the methylation level of
solute carrier family 26 member 4 (SLC26A4) predicted an increased risk of
presbycusis was investigated. Peripheral blood samples from 102 patients with
presbycusis and 104 controls were collected, and the methylation of the CpG sites
of SLC26A4 was measured by applying pyrosequencing technology combined with
sodium bisulfate DNA conversion chemistry. Within the SLC26A4 promoter region,
one CpG site (CpG3) exhibited a significantly (P<0.0001) greater methylation
level in the patients with presbycusis (26.5+/-5.56%) compared with the controls
(23.8+/-3.85%). Significantly different CpG3 methylation levels were observed
between the patients with presbycusis and the controls among the male
participants (P=0.0004). In addition, a significant decrease in the
transcriptional level of SLC26A4 in peripheral blood was observed in the patients
with presbycusis compared with the controls. Furthermore, analyses of the
receiver operating characteristic (ROC) curves indicated that CpG3 methylation at
the SLC26A4 promoter predicted the risk of presbycusis in the male participants
(AUC=0.684, 95% CI=0.584-0.784, P=0.001). The results demonstrated the
significance of the CpG site methylation level of SLC26A4, and thus provides a
potential marker for the diagnosis of presbycusis.
PMID- 28498467
TI - Antibody to human alpha-fetoprotein inhibits cell growth of human hepatocellular
carcinoma cells by resuscitating the PTEN molecule: in vitro experiments.
AB - It has been proposed that alpha-fetoprotein (AFP) is a new member of the
intracellular signaling molecule family of the phosphoinositide 3-kinase
(PI3K)/AKT signaling pathway via interaction with the phosphatase and tensin
homolog (PTEN). In this study, the effects of anti-human AFP antibody on the
functions of PTEN were examined using an AFP-producing human hepatoma cell line.
The antibody caused significant inhibition of cell growth, compared to a normal
IgG control, with the accumulation of intracellular immune complexes followed by
significant reduction of cytosolic functional AFP. Decrease in the amount of AKT
phosphorylated on serine (S) 473 indicated that PI3K/AKT signaling was suppressed
in the cells. S380-phosphorylated PTEN increased markedly by the second day after
antibody treatment, with slight but significant increase in the PTEN protein
level. Since phosphorylation at S380 is critical for PTEN stability, the increase
in S380-phosphorylated PTEN indicated maintenance of the number of PTEN molecules
and the related potential to control PI3K/AKT signaling. p53 protein (P53)
significantly, but slightly increased during antibody treatment, because PTEN
expression increased the stability and function of P53 via both molecular
interactions. P53 phosphorylated at S20 or at S392 dramatically increased,
suggesting an increase in the stability, accumulation and activation of P53.
Glucose transporter 1 (GLUT1) increased immediately after antibody treatment,
pointing to a deficiency of glucose in the cells. Immunofluorescence cytology
revealed that antibody-treatment re-distributed GLUT1 molecules throughout the
cytoplasm with a reduction of their patchy localization on the cell surface. This
suggested that translocation of GLUT1 depends on the PI3K/AKT pathway, in
particular on PTEN expression. Antibody therapy targeted at AFP-producing tumor
cells showed an inhibitory effect on the PI3K/AKT pathway via the liberation,
restoration and functional stabilization of PTEN. PTEN simultaneously induced
both P53 activation and intracellular translocation of GLUT1, since these are
closely associated with PTEN.
PMID- 28498468
TI - MicroRNA-379-5p plays a tumor-suppressive role in human bladder cancer growth and
metastasis by directly targeting MDM2.
AB - Bladder cancer is the second most common urological malignancy in the US and is
the most frequently diagnosed urological malignancy in China. An increasing
amount of evidence indicates that microRNAs perform extremely important functions
in many biological processes related to the formation and progression of cancers,
including bladder cancer. Previous studies have reported that microRNA-379-5p
(miR-379-5p) is involved in tumour initiation and development in human cancers.
However, the expression pattern, biological functions and the underlying
mechanisms of miR-379-5p in bladder cancer remain unknown. The present study
demonstrated that the expression levels of miR-379-5p in bladder cancer tissues
and cell lines were lower than the levels in adjacent normal tissues and the
human bladder epithelial immortalized SV-HUC-1 cell line. Restoration of the
expression of miR-379-5p inhibited bladder cancer cell proliferation, migration
and invasion. Mouse double minute 2 (MDM2) was identified as a direct target gene
of miR-379-5p. Furthermore, similar to miR-379-5p overexpression in bladder
cancer cells, inhibition of MDM2 exerted tumor-suppressive effects. Rescue
experiments showed that upregulation of MDM2 reversed the inhibitory effects of
miR-379-5p on bladder cancer cell proliferation, migration and invasion. MDM2 was
highly expressed and inversely correlated with miR-379-5p expression in bladder
cancer tissues. These findings suggest that the miR-379-5p/MDM2 pathway plays an
important role in bladder cancer and could serve as a potential candidate for
bladder cancer therapeutics.
PMID- 28498469
TI - Expression of c-FLIP in a rat model of sepsis and its effects on endothelial
apoptosis.
AB - Sepsis is characterized by the impaired regulation of inflammatory responses.
Apoptosis is important in the pathogenesis of sepsis. Cellular FLICE-inhibitory
protein (c-FLIP) is a catalytically inactive caspase-8 homologue, which
negatively interferes with apoptotic signaling. The role of c-FLIP in sepsis and
in endothelial cell apoptosis, a critical step in the pathogenesis of sepsis,
remains controversial. In the present study, to investigate the relationship
between c-FLIP and sepsis, a rat model of sepsis was induced by cecal ligation
and puncture, and western blot analysis was used to detect the expression of c
FLIPL, the long isoform of c-FLIP. Lower protein expression levels of c-FLIPL
were found in the brain, intestine and lung of the rat sepsis model, compared
with the rats in the sham surgery group. The association between the expression
of c-FLIPL and endothelial cell apoptosis was further examined in vitro by c
FLIPL overexpression and flow cytometry, which demonstrated that the expression
of c-FLIPL was inversely correlated with endothelial cell apoptosis. These data
suggested that c-FLIP may be important in sepsis and shed light on therapeutic
strategies.
PMID- 28498470
TI - Novel role of semaphorin 3A in the growth and progression of hepatocellular
carcinoma.
AB - Semaphorin 3A (SEMA3A), a secretory protein, is a founding member of the
semaphorin family and functions in both the biological behavior of tumor cells
and the modulation of tumor-associated macrophages. However, the role of SEMA3A
in hepatocellular carcinoma (HCC) is still not well established. In the present
study, we investigated the expression levels of SEMA3A in 80 HCC tissues and cell
lines, using RT-qPCR, western blotting and immunohistochemistry. Expression
profile analysis revealed that SEMA3A was significantly overexpressed in human
HCC patients and positively correlated with the metastatic potential of HCC
cells. Lentiviral transfection into PLC/PRF/5 and HCCLM3 cells was performed to
stably upregulate and downregulate the expression of SEMA3A in HCC cells. Cell
Counting Kit-8 (CCK-8), wound-healing and invasion assays revealed that SEMA3A
promoted the proliferation and migration of HCC cells in vitro. Proteome profiler
antibody microarray analysis revealed that overexpression of SEMA3A in HCC cells
induced a significant increase in the expression levels of gelsolin-like capping
protein (CapG), galectin-3, enolase 2 and epithelial cell adhesion molecule
(EpCAM). Furthermore, the upregulation of SEMA3A in HCC cells promoted tumor
growth and progression in an HCC mouse model. These results indicate that SEMA3A
enhances CapG, galectin-3, enolase 2 and EpCAM expression to promote HCC
progression and is a potential therapeutic target for HCC.
PMID- 28498471
TI - Sodium tanshinone IIA sulfonate improves inflammation, aortic endothelial cell
apoptosis, disseminated intravascular coagulation and multiple organ damage in a
rat heat stroke model.
AB - The aim of the present study was to investigate the effects of sodium tanshinone
IIA sulfonate (STS) on inflammatory responses, aortic endothelial cell apoptosis,
disseminated intravascular coagulation (DIC) and multiple organ damage in an
animal model of classic heat stroke (CHS). The rats in the heat stroke (HS) and
STS-treated heat stroke (STS-HS) groups were placed into a pre-warmed animal
temperature controller (ATC) at 35C. The moment at which the rectal temperature
reached 43.5C was considered as the time of onset of HS. In the HS groups, the
rats were removed from the ATC and allowed to recover at 26C for 0, 2, 6 or 12 h.
In the STS-HS groups, the rats received femoral vein injections of 5-40 mg/kg STS
immediately following the onset of HS and were subsequently placed at a
temperature of 26C to recover for 6 h. In the present study, the serum levels of
tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 were assessed
using ELISA, and the numbers of apoptotic aortic endothelial cells were
investigated using terminal deoxynucleotidyl transferase deoxyuridine
triphosphate nick-end labeling combined with immunofluorescence. In the HS
groups, the serum levels of TNF-alpha, IL-1beta and IL-6, as well as the numbers
of apoptotic aortic endothelial cells were increased compared with the
normothermic control group. Additionally, the plasma prothrombin time, activated
partial thromboplastin time and D-dimer level were significantly increased in the
HS group compared with the normothermic control group following recovery for 6 h.
By contrast, the platelet count was decreased in the HS group compared with the
normothermic control group. The serum levels of creatinine, blood urea nitrogen,
alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and
lactate dehydrogenase were increased and histopathological damage to multiple
organs was observed in the HS group following recovery for 6 h. In the STS-HS
groups, cytokine levels and apoptotic aortic endothelial cell numbers were
reduced compared with the HS group after 6 h recovery. STS (40 mg/kg) treatment
additionally improved the serum levels of organ injury indicators and plasma
indicators of coagulopathy, and prevented histopathological damage to multiple
organs. These findings demonstrated that STS treatment may ameliorate multiple
organ damage by attenuating inflammatory responses, aortic endothelial cell
apoptosis and DIC in CHS. These results suggested that STS may hold potential as
an alternative therapeutic strategy for the treatment of patients with HS.
PMID- 28498472
TI - Salinomycin induces endoplasmic reticulum stress-mediated autophagy and apoptosis
through generation of reactive oxygen species in human glioma U87MG cells.
AB - Salinomycin is a polyether ionophore antibiotic that has recently been shown to
induce cell apoptosis in human cancer cells displaying multiple mechanisms of
drug resistance. In the present study, we explored the impact of salinomycin on
the apoptosis and autophagy as well as the correlation between those effects and
endoplasmic reticulum (ER) stress molecular mechanisms in human glioma U87MG
cells. Apoptosis, autophagy and reactive oxygen species (ROS) were analyzed using
flow cytometry. In addition, expression levels of apoptosis-, autophagy- and ER
stress-related proteins were determined by western blotting. The results showed
that salinomycin induced apoptosis, ER stress and autophagy in glioma cancer cell
lines. In addition, salinomycin also induced ROS generation, and the ROS
scavenger N-acetyl-L-cysteine was found to inhibit the salinomycin-induced
apoptosis, ER stress and autophagy. The inhibition of ER stress with 4
phenylbutyric acid depressed salinomycin-induced apoptosis and autophagy.
Salinomycin increased the expression of autophagy marker protein, LC3B, and
accumulation of acidic vesicular organelles. Furthermore, pre-treatment with the
autophagy inhibitor 3-methyladenine showed potential in increasing the apoptosis
rate induced by salinomycin in the U87MG cells. Taken together, these results
revealed that salinomycin induced apoptosis and autophagy via ER stress mediated
by ROS, suggesting that ER stress by salinomycin plays a dual function in both
promoting and suppressing cell death.
PMID- 28498473
TI - Sulforaphane sensitizes human cholangiocarcinoma to cisplatin via the
downregulation of anti-apoptotic proteins.
AB - Cholangiocarcinoma (CCC) is an aggressive malignancy with poor therapeutic
options and pronounced chemotherapy resistance. The bioactive broccoli substance,
sulforaphane (SFN), is a promising new therapeutic option since it has been found
to induce therapeutic effects in both experimental and epidemiological studies in
various tumor entities. Thus, the present study was designed to assess the effect
of SFN on cisplatin sensitivity in CCC. Human HuCCT-1 and TFK-1 cells,
representing intrahepatic and extrahepatic CCC, respectively, were treated with
cisplatin and SFN. Viability, the platinated DNA content, and apoptosis were
assessed using both MTT assay and flow cytometry, while western blotting was used
to analyze the expression of proteins involved in apoptosis and DNA damage.
Whereas cisplatin was largely ineffective, SFN only therapy significantly
decreased the viability of both CCC cell lines. The combination of SFN with
cisplatin increased cisplatin cytotoxicity, which was particularly pronounced
relatively early at 36 h after treatment. Apoptosis, which was reflected by the
cleavage of caspase-3 and PARP, was significantly enhanced. Notably, only
cisplatin was found to induce the expression of proteins involved in the DNA
damage response; however, the presence of SFN appeared to enable otherwise
cisplatin-resistant cells to undergo apoptosis. Due to the fact that SFN did not
enhance the DNA platination levels upon cisplatin treatment, SFN may have exerted
its activity via the inhibition of the anti-apoptotic proteins Bcl-2 and XIAP, as
we observed. Data presented in the present study clearly demonstrated that SFN
significantly decreased the drug resistance to cisplatin in human CCC. This
highlights dietary co-treatment as a viable new treatment option for CCC.
PMID- 28498474
TI - Effect of miR-1244 on cisplatin-treated non-small cell lung cancer via MEF2D
expression.
AB - The aim of this study was to investigate the function of miR-1244 in cisplatin
treated non-small cell lung cancer (NSCLC). The results of quantitative PCR
analysis revealed that the expression levels of miR-1244 in cisplatin-treated
A549 and NCI-H522 human lung cancer cell lines were lower than those in untreated
A549 and NCI-H522 cells. Similarly, the expression level of miR-1244 in NSCLC
tissue samples from cisplatin-treated patients was also lower than that in non
cisplatin-treated NSCLC patients. Notably, the overall survival times of
cisplatin-treated NSCLC patients with high miR-1244 expression were superior to
those patients with low miR-1244 expression. We found that overexpression of miR
1244 suppressed cell viability and increased LDH toxicity in cisplatin-treated
A549 and NCI-H522 cells. Additionally, overexpression of miR-1244 induced the
apoptosis of cisplatin-treated A549 and NCI-H522 cells. Furthermore,
overexpression of miR-1244 promoted caspase-3 activity and p53 and Bax protein
expression, and suppressed myocyte enhancer factor 2D (MEF2D) and cyclin D1
protein expression in cisplatin-treated A549 and NCI-H522 cells. Small
interfering RNA (siRNA) targeting MEF2D suppressed the protein expression of
MEF2D, and was able to decrease the proliferation, promote caspase-3 activity,
p53 and Bax protein expression and inhibit cyclin D1 protein expression in
cisplatin-treated A549 and NCI-H522 cells following the overexpression of miR
1244. In summary, we found that miR-1244 affected cisplatin-treated NSCLC via
MEF2D expression.
PMID- 28498476
TI - Effects of unfractionated heparin and rivaroxaban on the expression of heparanase
and fibroblast growth factor 2 in human osteoblasts.
AB - Long-term treatment with anticoagulants may contribute to osteoporosis. Although
unfractionated heparin and rivaroxaban have adverse effects on bone
microstructure and function in adult rats, the underlying mechanism remains to be
elucidated. Heparanase (HPSE) and fibroblast growth factor (FGF)2 are important
signals in bone formation and fracture healing. Therefore, the present study was
designed to investigate the effects of unfractionated heparin and rivaroxaban on
the expression of HPSE and FGF2 in human osteoblasts. Human osteoblasts were
treated with unfractionated heparin (0.5-50 IU/ml) or rivaroxaban (0.13-13 ug/ml)
for different durations. Plasmids encoding HPSE and FGF2 were transfected into
osteoblasts, and cell viability was assessed using MTT assays, with mRNA and
protein expression levels determined using reverse transcription-quantitative
polymerase chain reaction and western blot analyses, respectively. Osteoblast
growth was significantly inhibited by treatment with unfractionated heparin (50
IU/ml) or rivaroxaban (13 ug/ml). Unfractionated heparin alone significantly
inhibited the expression of HPSE and FGF2, whereas rivaroxaban inhibited the
expression of FGF2 without affecting that of HPSE. Furthermore, the
overexpression of HPSE or FGF2 significantly reversed the inhibitory effects of
unfractionated heparin and rivaroxaban on osteoblasts. These findings suggested
that HPSE and FGF2 signals were involved in the detrimental role of
unfractionated heparin and rivaroxaban in human osteoblasts, providing novel
information on the side effects of anticoagulants.
PMID- 28498475
TI - Targeting hexokinase 2 inhibition promotes radiosensitization in HPV16 E7-induced
cervical cancer and suppresses tumor growth.
AB - In order to improve the sensitivity of cervical cancer cells to irradiation
therapy, we targeted hexokinase 2 (HK2), the first rate-limiting enzyme of
glycolysis, and explore its role in cervical cancer cells. We suppressed HK2
expression and/or function by shRNA and/or metformin and found HK2 inhibition
enhanced cells apoptosis with accelerating expression of cleaved PARP and caspase
3. HK2 inhibition also induced much inferior proliferation of cervical cancer
cells both in vitro and in vivo with diminishing expression of mTOR, MIB and
MGMT. Moreover, HK2 inhibition altered the metabolic profile of cervical cancer
cells to one less dependent on glycolysis with a reinforcement of mitochondrial
function and an ablation of lactification ability. Importantly, cervical cancer
cells contained HK2 inhibition displayed more sensitivity to irradiation. Further
results indicated that HPV16 E7 oncoprotein altered the glucose homeostasis of
cervical cancer cells into glycolysis by coordinately promoting HK2 expression
and its downregulation of glycolysis. Taken together, our findings supported a
mechanism whereby targeting HK2 inhibition contributed to suppress HPV16 E7
induced tumor glycolysis metabolism phenotype, inhibiting tumor growth, and
induced apoptosis, blocking the cancer cell energy sources and ultimately
enhanced the sensitivity of HPV(+) cervical cancer cells to irradiation therapy.
PMID- 28498477
TI - Identification of candidate substrates of ubiquitin-specific protease 13 using 2D
DIGE.
AB - The present study aimed to identify candidate substrates of ubiquitin-specific
protease (USP)13 using two-dimensional fluorescence difference gel
electrophoresis (2D-DIGE). USP13 is a well-characterized member of the USP
family, which regulates diverse cellular functions by cleaving ubiquitin from
ubiquitinated protein substrates. However, existing studies indicate that USP13
has no detectable hydrolytic activity in vitro. This finding implies that USP13
likely has different substrate specificity. In this study, a USP cleavage assay
was performed using two different types of model substrates (glutathione S
transferase-Ub52 and ubiquitin-beta-galactosidase) to detect the deubiquitinating
enzyme (DUB) activity of USP13. In addition, a proteomic approach was taken by
using 2D-DIGE to detect cellular proteins whose expressoin is significantly
altered in 293T cell lines following the overexpression of USP13 or its C345S
mutant (the catalytically inactive form). The data indicated that USP13 still has
no detectable DUB activity in vitro nor does C345S. The results of 2D-DIGE
demonstrated that the expression of several proteins increased or decreased
significantly in 293T cells following the overexpression of USP13. Mass spec
troscopy analysis of gel spots identified 7 proteins, including 4 proteins with
an increased expression, namely vinculin, thimet oligopeptidase, cleavage and
polyadenylation specific factor 3, and methylosome protein 50, and 3 proteins
with a decreased expression, namely adenylosuccinate synthetase, annexin and
phosphoglycerate mutase. In addition, in the samples of 293T cell lines after the
overexpression of USP13 and USP13 C345S, vinculin exhibited an increased
expression, suggesting that it may be a candidate substrate of USP13. However,
sufficient follow-up validation studies are required in order to determine
whether vinculin protein directly interacts with USP13.
PMID- 28498478
TI - Demethylation of miR-495 inhibits cell proliferation, migration and promotes
apoptosis by targeting STAT-3 in breast cancer.
AB - In breast cancer (BC), silencing of miRNA genes due to miRNA gene promoter
methylation are the important mechanisms directly contributing to tumorigenesis
and tumor progression. miRNA-495 (miR-495) has been reported to be a tumor
suppressor gene in various cancers, but its role and regulation in BC remains
unclear. In the present study, the level of miR-495 was inversely correlated with
the expression of STAT-3 in BC tissues and cell lines. miR-495 can directly
target 3'-UTR of STAT-3 mRNA and thereby decrease the expression of STAT-3 in MCF
7 and HCC1973 cells by Targetscan and Dual-luciferase assay. We further analyzed
miR-495 promoter methylation by sodium bisulfite sequencing method (BSP), and
found DNA methyltransferase inhibitor, 5-AzaC concomitantly upregulated
expression of miR-495 and downregulated its target gene STAT-3 and its downstream
target VEGF. Furthermore, we further observed that 5-AzaC treatment, miR-495
mimics and STAT-3 knockdown significantly inhibited cell function in breast
cancer by Transwell assay, EdU flow cytometry, Annexin V-FITC/PI combined with
flow cytometry and Hoechst staining. Taken together, our data are first to
demonstrate that the miR-495 is silenced due to promoter methylation in breast
cancer. DNA methyltransferase inhibitor 5-AzaC could reverse miR-495 (suppressor
gene) and STAT-3 (oncogene). The anticancer properties of 5-AzaC were
preliminarily confirmed in breast cancer.
PMID- 28498479
TI - PPAR-alpha improves the recovery of lung function following acute respiratory
distress syndrome by suppressing the level of TGF-beta1.
AB - Although peroxisome proliferator-activated receptor (PPAR)-alpha has been
reported to be involved in preventing acute lung injury (ALI), the molecular
regulation of post-ALI lung recovery remains to be fully elucidated. The aim of
the present study was to characterize the mechanism by which PPAR-alpha prevents
ALI and examine the role of PPAR-alpha in the recovery of lung function following
acute respiratory distress syndrome (ARDS). Reverse transcription-quantitative
polymerase chain reaction and western blot analyses suggested that PPAR-alpha was
effective in suppressing transforming growth factor (TGF)-beta1 in HLF cells and
RAW 264.7 cells. In an ALI mouse model, PPAR-alpha treatment prior to stimulation
with lipopolysaccharide (LPS) resulted in a decrease in the expression of TGF
beta1 in bronchoalveolar lavage fluid (BALF), peripheral blood and splenocytes.
The injection of a virus expressing short hairpin PPAR-alpha into mice following
LPS treatment resulted in a dose-dependent increase in lung resistance index and
decrease in dynamic compliance, and a significant increase in BALF protein, which
indicated PPAR-alpha was essential for the recovery of lung function following
ALI. Of note, the serum expression of PPAR-alpha was inversely correlated with
TGF-beta1 and negatively correlated with disease severity in patients with ARDS.
These data suggested that PPAR-alpha was essential for the recovery of lung
function following ALI by the suppression of TGF-beta1, which reveals a
previously unappreciated mechanism controlling post-ALI lung recovery.
PMID- 28498480
TI - Miconazole induces apoptosis via the death receptor 5-dependent and mitochondrial
mediated pathways in human bladder cancer cells.
AB - Miconazole (MIC), an antifungal agent, diplays anti-tumorigenic activity in
various types of human cancers, including bladder cancer, yet its mechanism of
antitumor action is not well understood. In the present study, we demonstrated
that, in a cell viability assay, MIC had a cytotoxic effect on human T24, J82 and
TSGH-8301 bladder cancer cells in a dose- and time-dependent manner, but did not
exhibit significant toxicity toward human peripheral blood mononuclear cells.
Cell cycle analysis revealed that MIC at concentrations of 25 and 50 uM
significantly caused G0/G1 arrest in the TSGH-8301 and T24 cells, respectively.
DNA fragmentation, mitochondrial membrane potential and western blot analyses
showed that MIC inhibited the growth of these cells by both mitochondrial
mediated and death receptor (DR5)-mediated apoptosis pathways. Specifically, MIC
increased the protein levels of p21 and p27, but decreased the expression of
cyclin E1, CDK2 and CDK4. MIC augmented the expression of DR5, cleaved forms of
caspase-3 -8 and -9, poly(ADP-ribose) polymerase and Bax, decreased the
expression of Bcl-2 but increased cytosol levels of cytochrome c. Our results
suggest that MIC inhibits the growth of bladder cancer cells through induction of
G0/G1 arrest and apoptosis via activation of both the extrinsic and intrinsic
apoptotic pathways. MIC is a potential chemotherapeutic agent for treating
bladder cancer in humans.
PMID- 28498482
TI - Effects of an antenatal lifestyle intervention on offspring obesity - a 5-year
follow-up of a randomized controlled trial.
AB - INTRODUCTION: Strategies to limit excessive maternal gestational weight gain
could also have positive health effects for the offspring. This study informs us
on the effect of an antenatal lifestyle intervention on offspring body mass index
(BMI) trajectory until age five. MATERIAL AND METHODS: A secondary analysis of a
randomized controlled trial aimed at reducing gestational weight gain, set in
Orebro, Sweden (Clinical Trials.gov Id NCT00451425). Offspring were followed with
standardized measures of weight and height until age five. Mean BMI z-score and
proportion (%) of over- and undernutrition (BMI z-score > +/- 2 standard
deviations) was compared between groups. Risk estimates for obesity at age five
were analyzed in relation to maternal gestational weight gain and prepregnancy
BMI as a secondary outcome. RESULTS: We analyzed 374 children at birth and 300 at
age five. No significant difference in mean BMI z-score was seen at birth (0.68
(I) vs 0.56 (C), p = 0.242) or at age five (0.34 (I) vs 0.26 (C), p = 0.510) and
no significant difference in proportion of over- or undernutrition was seen.
Excessive maternal gestational weight gain was an independent risk factor for
offspring obesity at birth (OR = 4.51, p < 0.001) but not at age five. Maternal
obesity was an independent risk factor for offspring obesity at age five (OR =
4.81, p = 0.006). CONCLUSIONS: Our composite antenatal lifestyle intervention did
not significantly reduce the risk of obesity in offspring up until age five.
PMID- 28498481
TI - Comparison of three different methods for the detection of circulating tumor
cells in mice with lung metastasis.
AB - Circulating tumor cells (CTCs) represent the key step of cancer cell
dissemination. The alteration of CTCs correlates with the treatment outcome and
prognosis. To enrich and identify CTCs from billions of blood cells renders a
very challenging task, which triggers development of several methods, including
lysis of RBC plus negative or positive enrichment using antibodies, and filter
membrane or spiral microfluidics to capture CTCs. To compare the advantages of
different enrichment methods for CTCs, we utilized the 4T1 breast cancer cells
transfected with both green fluorescent protein (GFP) and luciferase to trace
CTCs in the experimental lung metastasis model. Three methods were used to detect
CTCs at the same time: bioluminescence assay, smearing method, and membrane
filter method. The in vivo alive mouse imaging was used to dynamically monitor
the growth of lung metastases. The sensitivity and accuracy of three detection
methods were compared side-by-side. Our results showed that 1) the sensitivity of
bioluminescence assay was the highest, but there was no information of CTC
morphology; 2) the smearing method and membrane filter method could observe the
detail of CTC morphology, such as in single or in cluster, while their
sensitivity was lower than bioluminescence assay; 3) A dynamic observation at a 7
day intervals, the lung metastatic cancer grew at a log speed, while CTCs were
increased at a low speed. This might be due to the activated immune cells
eliminating the CTCs at a speed much faster than CTCs were generated. This
comparison of three CTC detection methods in mouse model suggests that
bioluminescence assay could be used in quantitative study of the effect of
certain agent on the suppression of CTCs, while GFP-based morphological assays
could be used to study the dissemination mechanism of CTCs. The combination of
both bioluminescence assay and GFP-based assay would generate more information
for quantity and quality of CTCs.
PMID- 28498483
TI - Reflectance confocal microscopy in the evaluation of targetoid haemosiderotic
haemangioma apropos two cases.
PMID- 28498484
TI - Sinkholes Due to Groundwater Withdrawal in Tazerbo Wellfield, SE Libya.
AB - The desert of eastern Libya forms one of the most arid regions of the Sahara. The
Great Man-Made River Project (GMRP) was established. It transports millions of
cubic meters of water a day from desert wellfields to the coastal cities, where
over 80% of the population lives. The Tazerbo Wellfield is one of the wellfields
designed within the GMRP, delivering water to the eastern coast of Libya through
an underground pipe network. Tazerbo Wellfield consists of 108 production wells;
each well was designed to pump 100 L/s. The planned total groundwater withdrawal
from all wells is 1 million m3 /d. The deep sandstone aquifer (Nubian sandstone)
is covered by a thick mudstone-siltstone aquitard and is being heavily pumped.
The aquifer and fine-grained sediments of the aquitard may be compacted resulting
in land subsidence as a result of high exploitation. Local sinkholes have
developed in the area of Tazerbo since the start of the pumping from the
wellfield in 2004. These sinkholes have been caused mainly by lowering of the
piezometric heads due to the withdrawal of groundwater. In this study, a
hydrogeological investigation is presented about the effect of large groundwater
pumping from the Nubian sandstone aquifer in Tazerbo Wellfield, SE Libya, based
on physical parameters for 108 production wells and 23 observation wells.
PMID- 28498485
TI - Transient Recharge Estimability Through Field-Scale Groundwater Model
Calibration.
AB - The estimation of recharge through groundwater model calibration is hampered by
the nonuniqueness of recharge and aquifer parameter values. It has been shown
recently that the estimability of spatially distributed recharge through
calibration of steady-state models for practical situations (i.e., real-world,
field-scale aquifer settings) is limited by the need for excessive amounts of
hydraulic-parameter and groundwater-level data. However, the extent to which
temporal recharge variability can be informed through transient model
calibration, which involves larger water-level datasets, but requires the
additional consideration of storage parameters, is presently unknown for
practical situations. In this study, time-varying recharge estimates, inferred
through calibration of a field-scale highly parameterized groundwater model, are
systematically investigated subject to changes in (1) the degree to which
hydraulic parameters including hydraulic conductivity (K) and specific yield (Sy
) are constrained, (2) the number of water-level calibration targets, and (3) the
temporal resolution (up to monthly time steps) at which recharge is estimated.
The analysis involves the use of a synthetic reality (a reference model) based on
a groundwater model of Uley South Basin, South Australia. Identifiability
statistics are used to evaluate the ability of recharge and hydraulic parameters
to be estimated uniquely. Results show that reasonable estimates of monthly
recharge (<30% recharge root-mean-squared error) require a considerable amount of
transient water-level data, and that the spatial distribution of K is known.
Joint estimation of recharge, Sy and K, however, precludes reasonable inference
of recharge and hydraulic parameter values. We conclude that the estimation of
temporal recharge variability through calibration may be impractical for real
world settings.
PMID- 28498486
TI - The authors respond.
PMID- 28498487
TI - The malleus to oval window revision stapedotomy: Efficacy and longitudinal study
outcome.
AB - OBJECTIVE: To determine the longitudinal effectiveness of the malleus to oval
window stapedotomy technique among patients undergoing revision surgery when the
incus is unavailable. STUDY DESIGN: Retrospective, case series. METHODS: Charts
of 15 patients who underwent 17 malleus attachment stapedotomies performed by a
single surgeon from 2000 to 2015 were reviewed. Surgery was ambulatory,
transcanal, with laser technique, and under local anesthesia. RESULTS: Of 17
stapedotomies performed, there were nine first revisions, six second revisions,
one third revision, and one fourth revision. There were no surgical
complications. Mean preoperative air-bone gap (ABG) was 32.3 dB. Mean
postoperative ABG at 6 months was 10.7 dB, and at last follow-up was 16.3 dB.
Average length of follow-up was 36.5 months. At last follow-up, 100% of first
revisions achieved ABG <= 20 dB (77.8% <= 10 dB), compared to 50% of second
revisions with ABG <= 20 dB (none <= 10 dB), and 0% of third or fourth revisions
with ABG <= 20 dB. Trend lines for second and third/fourth revisions showed a
deterioration (widening) in postoperative ABG by 0.18 and 0.72 dB per month,
respectively. The first-revision trend line, conversely, showed negligible change
with time, demonstrating the superior durability of first revisions compared to
subsequent surgeries. CONCLUSION: The malleus to oval window stapedotomy
technique is more effective and longer lasting in first-revision surgery compared
to subsequent procedures. Standard or implantable amplification devices may be
preferable for patients with multiple prior procedures. LEVEL OF EVIDENCE: 4.
Laryngoscope, 128:461-467, 2018.
PMID- 28498488
TI - Slotted labyrinthotomy approach with customized electrode for patients with
common cavity deformity.
AB - OBJECTIVES/HYPOTHESIS: Cochlear implantation for patients with common cavity
deformity (CCD) can be difficult, with a higher incidence of intra- and
postoperative complications; outcomes with CCD patients are also highly variable.
In this study, surgical time was compared between the traditional facial recess
approach (TFRA) and the transmastoid slotted labyrinthotomy approach (TSLA).
Audiological outcomes and the benefit of using customized electrode arrays for
CCD patients are also discussed. STUDY DESIGN: Retrospective review of 13
cochlear implant (CI) patients with CCD. METHODS: Six patients were implanted
with the TFRA using traditional electrodes, and seven patients were implanted
with the TSLA using customized electrodes. Intra- and postoperative complications
were reviewed. Audiological outcomes were measured 3 months to 2 years after CI
activation. RESULTS: The mean surgical time for TSLA group was nearly half as
long as for the TRFA group (P < .05). Although mean audiological outcomes were
better for the TSLA group, there was no significant difference between groups (P
> .05). CONCLUSIONS: For CCD patients, TSLA for cochlear implantation is
recommended due to shortened surgical time; customized electrode arrays may be
additionally advantageous in terms of audiological outcomes. LEVEL OF EVIDENCE:
4. Laryngoscope, 128:468-472, 2018.
PMID- 28498489
TI - Application of Edible Films Containing Oregano (Origanum vulgare) Essential Oil
on Queso Blanco Cheese Prepared with Flaxseed (Linum usitatissimum) Oil.
AB - Fortification of queso blanco (QB) with flaxseed oil (FO) containing omega-3
polyunsaturated fatty acids may provide a functional food with health benefits
such as improved cell, brain, and retina functionality, and protection against
cardiovascular and immune-inflammatory diseases. However, QB experiences a short
shelf life because of the early development of yeasts and molds and addition of
FO may increase susceptibility to lipid oxidation. Oregano essential oil (OEO) is
known for its antimicrobial and antioxidant properties, but due to its intense
flavor compounds it may not be suitable for direct incorporation into QB. Thus,
incorporation of OEO into an edible film prepared with whey protein isolate (WPI)
may improve the shelf life of QB. Scanning electron microscopy (SEM) micrographs
revealed that FO was successfully retained by the cheese after homogenization.
The thiobarbituric-acid-reactive-substances (TBARS) and yeast and mold counts
(YMC) of the wrapped cheeses were analyzed during 60 d of refrigerated storage.
The oxidation rate increased significantly for nonwrapped QB containing FO (QBFO)
during storage, however wrapping with WPI edible films containing OEO (WOF)
significantly limited lipid oxidation and prevented growth of yeasts and molds.
This study demonstrated the antioxidant and antimicrobial properties of WOF for
preservation of QBFO during refrigerated storage.
PMID- 28498490
TI - Multi-subgroup gene screening using semi-parametric hierarchical mixture models
and the optimal discovery procedure: Application to a randomized clinical trial
in multiple myeloma.
AB - This article proposes an efficient approach to screening genes associated with a
phenotypic variable of interest in genomic studies with subgroups. In order to
capture and detect various association profiles across subgroups, we flexibly
estimate the underlying effect size distribution across subgroups using a semi
parametric hierarchical mixture model for subgroup-specific summary statistics
from independent subgroups. We then perform gene ranking and selection using an
optimal discovery procedure based on the fitted model with control of false
discovery rate. Efficiency of the proposed approach, compared with that based on
standard regression models with covariates representing subgroups, is
demonstrated through application to a randomized clinical trial with microarray
gene expression data in multiple myeloma, and through a simulation experiment.
PMID- 28498491
TI - The blood cell family on a lymph node road.
PMID- 28498492
TI - Multiple roles of afadin in the ultrastructural morphogenesis of mouse
hippocampal mossy fiber synapses.
AB - A hippocampal mossy fiber synapse, which is implicated in learning and memory,
has a complex structure in which mossy fiber boutons attach to the dendritic
shaft by puncta adherentia junctions (PAJs) and wrap around a multiply-branched
spine, forming synaptic junctions. Here, we electron microscopically analyzed the
ultrastructure of this synapse in afadin-deficient mice. Transmission electron
microscopy analysis revealed that typical PAJs with prominent symmetrical plasma
membrane darkening undercoated with the thick filamentous cytoskeleton were
observed in the control synapse, whereas in the afadin-deficient synapse,
atypical PAJs with the symmetrical plasma membrane darkening, which was much less
in thickness and darkness than those of the control typical PAJs, were observed.
Immunoelectron microscopy analysis revealed that nectin-1, nectin-3, and N
cadherin were localized at the control typical PAJs, whereas nectin-1 and nectin
3 were localized at the afadin-deficient atypical PAJs to extents lower than
those in the control synapse and N-cadherin was localized at their nonjunctional
flanking regions. These results indicate that the atypical PAJs are formed by
nectin-1 and nectin-3 independently of afadin and N-cadherin and that the typical
PAJs are formed by afadin and N-cadherin cooperatively with nectin-1 and nectin
3. Serial block face-scanning electron microscopy analysis revealed that the
complexity of postsynaptic spines and mossy fiber boutons, the number of spine
heads, the area of postsynaptic densities, and the density of synaptic vesicles
docked to active zones were decreased in the afadin-deficient synapse. These
results indicate that afadin plays multiple roles in the complex ultrastructural
morphogenesis of hippocampal mossy fiber synapses.
PMID- 28498493
TI - Involvement of microglia in early axoglial alterations of the optic nerve induced
by experimental glaucoma.
AB - Glaucoma is a leading cause of blindness, characterized by retinal ganglion cell
(RGC) loss and optic nerve (ON) damage. Cumulative evidence suggests glial cell
involvement in the degeneration of the ON and RGCs. We analyzed the contribution
of microglial reactivity to early axoglial alterations of the ON in an induced
model of ocular hypertension. For this purpose, vehicle or chondroitin sulfate
(CS) were weekly injected into the eye anterior chamber from Wistar rats for
different intervals. The amount of Brn3a(+) RGC significantly decreased in CS
injected eyes for 10 and 15 (but not 6) weeks. A reduction in anterograde
transport of beta-subunit cholera toxin was observed in the superior colliculus
and the lateral geniculate nucleus contralateral to CS-injected eyes for 6 and 15
weeks. A disruption of cholera toxin beta-subunit transport was observed at the
proximal myelinated ON. A significant decrease in phosphorylated neurofilament
heavy chain immunoreactivity, an increase in ionized calcium-binding adaptor
molecule 1(+), ED1(+) (microglial markers), and glial fibrillary acidic protein
(astrocytes) (+) area, and decreased luxol fast blue staining were observed in
the ON at 6 and 15 weeks of ocular hypertension. Microglial reactivity
involvement was examined through a daily treatment with minocycline (30 mg/kg,
i.p.) for 2 weeks, after 4 weeks of ocular hypertension. Minocycline prevented
the increase in ionized calcium-binding adaptor molecule 1(+), ED-1(+), and glial
fibrillary acidic protein(+) area, the decrease in phosphorylated neurofilament
heavy-chain immunoreactivity and luxol fast blue staining, and the deficit in
anterograde transport induced by 6 weeks of ocular hypertension. Thus, targeting
microglial reactivity might prevent early axoglial alterations in the
glaucomatous ON. Cover Image for this issue: doi: 10.1111/jnc.13807.
PMID- 28498494
TI - A Mercaptoacetamide-Based Class II Histone Deacetylase Inhibitor Suppresses Cell
Migration and Invasion in Monomorphic Malignant Human Glioma Cells by Inhibiting
FAK/STAT3 Signaling.
AB - Histone deacetylase inhibitors (HDACIs) have emerged as potential anticancer
agents for the treatment of solid and hematopoietic cancers. Several HDACIs delay
cell growth, induce differentiation, or activate apoptosis in multiple types of
tumors, including glioblastomas. In the present study, we showed that the
mercaptoacetamide-based HDACI W2 inhibits cell migration and invasion in
monomorphic malignant human glioma cells. W2 treatment significantly decreased
the activity and expression levels of matrix metalloprotease-2 in malignant A172
cells but not in U373MG cells. Key signaling pathways involved in cell migration
and invasion, including PI3K-AKT, ERK-JNK-P38, and FAK/STAT3, were examined to
identify the mechanism of action of W2. W2 increased the phosphorylation of AKT
and altered cell migration and invasion in an AKT-independent manner. W2
inhibited the phosphorylation of FAK/STAT3, and treatment with a FAK/STAT3
inhibitor significantly suppressed cancer cell migration and MMP-2 activity in
the presence of W2. In addition, W2 significantly inhibited the nuclear
translocation of phospho-STAT3. Taken together, our results suggest that W2
suppresses cancer cell migration and invasion by inhibiting FAK/STAT3 signaling
and STAT3 translocation to the nucleus in monomorphic malignant human glioma
cells. J. Cell. Biochem. 118: 4672-4685, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28498495
TI - Oleaginous yeasts: Promising platforms for the production of oleochemicals and
biofuels.
AB - Oleaginous yeasts have a unique physiology that makes them the best suited hosts
for the production of lipids, oleochemicals, and diesel-like fuels. Their high
lipogenesis, capability of growing on many different carbon sources (including
lignocellulosic sugars), easy large-scale cultivation, and an increasing number
of genetic tools are some of the advantages that have encouraged their use to
develop sustainable processes. This mini-review summarizes the metabolic
engineering strategies developed in oleaginous yeasts within the last 2 years to
improve process metrics (titer, yield, and productivity) for the production of
lipids, free fatty acids, fatty acid-based chemicals (e.g., fatty alcohols, fatty
acid ethyl esters), and alkanes. During this short period of time, tremendous
progress has been made in Yarrowia lipolytica, the model oleaginous yeast, which
has been engineered to improve lipid production by different strategies including
increasing lipogenic pathway flux and biosynthetic precursors, and blocking
degradation pathways. Moreover, remarkable advances have also been reported in
Rhodosporidium toruloides and Lipomyces starkey despite the limited genetic tools
available for these two very promising hosts. Biotechnol. Bioeng. 2017;114: 1915
1920. (c) 2017 Wiley Periodicals, Inc.
PMID- 28498496
TI - The author responds.
PMID- 28498497
TI - The aggravation of arthritis by periodontitis is dependent of IL-17 receptor A
activation.
AB - AIM: To evaluate whether Porphyromonas gingivalis-induced periodontitis
aggravates the antigen-induced arthritis (AIA) model, and whether this effect is
dependent on the Th17/IL-17 signalling pathway. MATERIALS AND METHODS: Antigen
induced arthritis was triggered by local injection of methylated bovine serum
albumin into the knee joint of previously immunized C57BL/6 wild-type (WT) and IL
17 receptor A (IL-17RA)-knockout mice. Periodontal disease in naive or arthritic
mice was induced by oral infection with P. gingivalis. Animals were sacrificed 7,
15 and 30 days after infection. Alveolar bone loss, joint histopathology,
articular hyperalgesia and joint cytokine production were assessed, in addition
to the proportion of Th17 and Treg cells isolated from the inguinal lymph nodes.
RESULTS: No influence of experimentally-induced arthritis was found on the
alveolar bone resorption induced by P. gingivalis. However, mice with
experimentally-induced arthritis that were exposed to P. gingivalis presented
higher joint damage and Th17 frequencies when compared to non-infected mice. The
aggravation of arthritis by periodontitis was accompanied by increased TNF and IL
17 production and articular neutrophil infiltration, whereas arthritis
aggravation and changes in neutrophil infiltration were absent in IL-17RA
deficient mice. CONCLUSION: The effects of P. gingivalis-induced periodontitis on
arthritis are dependent on Th17 expansion and IL-17RA signalling, which lead to
increased neutrophil infiltration into the joints.
PMID- 28498498
TI - Impact of prescription drug monitoring programs (PDMPs) on opioid utilization
among Medicare beneficiaries in 10 US States.
AB - BACKGROUND AND AIMS: Prescription Drug Monitoring Programs (PDMPs) are a
principal strategy used in the United States to address prescription drug abuse.
We (1) compared opioid use pre- and post-PDMP implementation and (2) estimated
differences of PDMP impact by reason for Medicare eligibility and plan type.
DESIGN: Analysis of opioid prescription claims in US states that implemented
PDMPs relative to non-PDMP states during 2007-12. SETTING: Florida, Louisiana,
Nebraska, New Jersey, Vermont, Georgia, Wisconsin, Maryland, New Hampshire and
Arkansas, USA. PARTICIPANTS: A total of 310 105 disabled and older adult Medicare
enrolees. MEASUREMENTS: Primary outcomes were monthly total opioid volume, mean
daily morphine milligram equivalent (MME) dose per prescription and number of
opioid prescriptions dispensed. The key predictors were PDMP status and time.
Tests for moderation examined PDMP impact by Medicare eligibility (disability
versus age) and drug plan [privately provided Medicare Advantage (MAPD) versus
fee-for-service (PDP)]. FINDINGS: Overall, PDMP implementation was associated
with reduced opioid volume [-2.36 kg/month, 95% confidence interval (CI) = -3.44,
-1.28] and no changes in mean MMEs or opioid prescriptions 12 months after
implementation compared with non-PDMP states. We found evidence of strong
moderation effects. In PDMP states, estimated monthly opioid volumes decreased
1.67 kg (95% CI = -2.38, -0.96) and 0.75 kg (95% CI = -1.32, -0.18) among
disabled and older adults, respectively, and 1.2 kg, regardless of plan type. MME
reductions were 3.73 mg/prescription (95% CI = -6.22, -1.24) in disabled and 3.02
mg/prescription (95% CI = -3.86, -2.18) in MAPD beneficiaries, but there were no
changes in older adults and PDP beneficiaries. Dispensed prescriptions increased
259/month (95% CI = 39, 479) among the disabled and decreased 610/month (95% CI =
-953, -257) among MAPD beneficiaries. CONCLUSIONS: Prescription drug monitoring
programs (PDMPs) are associated with reductions in opioid use, measured by
volume, among disabled and older adult Medicare beneficiaries in the United
States compared with states that do not have PDMPs. PDMP impact on daily doses
and daily prescriptions varied by reason for eligibility and plan type. These
findings cannot be generalized beyond the 10 US states studied.
PMID- 28498499
TI - Heterogeneous extracellular dopamine regulation in the subregions of the
olfactory tubercle.
AB - Recent studies show that dense dopamine (DA) innervation from the ventral
tegmental area to the olfactory tubercle (OT) may play an important role in
processing multisensory information pertaining to arousal and reward, yet little
is known about DA regulation in the OT. This is mainly due to the anatomical
limitations of conventional methods of determining DA dynamics in small
heterogeneous OT subregions located in the ventral most part of the brain.
Additionally, there is increasing awareness that anteromedial and anterolateral
subregions of the OT have distinct functional roles in natural and
psychostimulant drug reinforcement as well as in regulating other types of
behavioral responses, such as aversion. Here, we compared extracellular DA
regulation (release and clearance) in three subregions (anteromedial,
anterolateral, and posterior) of the OT of urethane-anesthetized rats, using in
vivo fast-scan cyclic voltammetry following electrical stimulation of ventral
tegmental area dopaminergic cell bodies. The neurochemical, anatomical, and
pharmacological evidence confirmed that the major electrically evoked
catecholamine in the OT was DA across both its anteroposterior and mediolateral
extent. While both D2 autoreceptors and DA transporters play important roles in
regulating DA evoked in OT subregions, DA in the anterolateral OT was regulated
less by the D2 receptors when compared to other OT subregions. Comparing previous
data from other DA rich ventral striatum regions, the slow DA clearance across
the OT subregions may lead to a high extracellular DA concentration and
contribute towards volume transmission. These differences in DA regulation in the
terminals of OT subregions and other limbic structures will help us understand
the neural regulatory mechanisms of DA in the OT, which may elucidate its
distinct functional contribution in the ventral striatum towards mediating
aversion, reward and addiction processes.
PMID- 28498500
TI - Socioeconomic disparities and comorbidities, not race, affect salivary gland
malignancy survival outcomes.
AB - OBJECTIVES/HYPOTHESIS: This study sought to determine whether comorbidities,
race, and socioeconomic factors affect 5- and 10-year survival outcomes for
patients with salivary gland malignancies treated at a single large academic
institution with a large African American population. STUDY DESIGN: A
retrospective cohort study was performed of all patients with salivary gland
malignancies, from 1990 to 2015, at a large academic medical center. METHODS:
Standard statistical analysis was performed using Kaplan-Meier survival curve
analysis and Cox proportional hazard models. RESULTS: The overall 5- and 10-year
survival rates decreased with age >= 60 years (P < .001), stage 3 or 4 (P <
.001), clinical T stage 3 or 4 (P < .001), and clinical N stage 1, 2, or 3 (P <
.001). Living in a ZIP code with an increasing proportion of residents with a
high school degree or less (P < .05), being male (P < .05), increasing age at the
time of diagnosis (P < .001), and increasing Charlson comorbidity index (P < .05)
detrimentally impacted survival at 5 and 10 years. Race was associated with
socioeconomic variables, but race was not a prognostic indicator of survival.
CONCLUSIONS: Socioeconomic factors and comorbidities, not race, were negative
prognostic indicators of survival of patients with salivary gland malignancies.
Using race as a marker for socioeconomic status should be used with caution.
LEVEL OF EVIDENCE: 4. Laryngoscope, 127:2545-2550, 2017.
PMID- 28498502
TI - Real-time three-dimensional jaw tracking in temporomandibular disorders.
AB - When a dysfunction occurs in any component of the stomatognathic system,
temporomandibular disorders (TMD) may originate. The aim of this study was to
compare the deviations, displacement and the execution speed of mandibular
movements among asymptomatic participants and those with TMD. Convenience
sampling was used; forty participants diagnosed by clinical evaluation following
the Research Diagnostic Criteria for Temporomandibular Disorders were divided
into three groups: arthropathy (GART, 10 participants, 40% men), myopathy (GMYO,
10 participants, 30% men), and the control group (CG, 20 asymptomatic
participants, 25% men). Participants were asked to perform the movements of free
maximal mouth opening and closing, right and left lateral excursions, and
protrusion with sliding teeth contacts. The mandibular trajectory was recorded
using opto-electronic devices tracking reflective markers placed in front of the
'soft tissue pogonion point'. The movements were analysed on the following axis:
x - medial-lateral, y - vertical, z - antero-posterior. Significative differences
were found in CGxGART - unassisted maximal mouth opening and closing projection
on y-axis (OCY), CGxGMYO - unassisted maximal mouth opening and closing
projection on x-axis (OCX), and in the measures Opening lateral deviation on x
axis (OLDX), closing lateral deviation on x-axis (CLDX) and in the measures of
speed for both. In regard to GARTxGMYO, a significative difference was found in
Protrusion lateral deviation on x-axis (PLDX) 'Conover-Iman Test of Multiple
Comparisons Using Rank Sums' using Bonferroni correction (P < 0.05). In
conclusion, the total opening movements in individuals with TMD tended to have
higher deviation than in those asymptomatic individuals and a reduction in the
speed of movements.
PMID- 28498501
TI - PPAR-gamma agonist pioglitazone modifies craving intensity and brain white matter
integrity in patients with primary cocaine use disorder: a double-blind
randomized controlled pilot trial.
AB - BACKGROUND AND AIMS: Pioglitazone (PIO), a potent agonist of PPAR-gamma, is a
promising candidate treatment for cocaine use disorder (CUD). We tested the
effects of PIO on targeted mechanisms relevant to CUD: cocaine craving and brain
white matter (WM) integrity. Feasibility, medication compliance and tolerability
were evaluated. DESIGN: Two-arm double-blind randomized controlled proof-of
concept pilot trial of PIO or placebo (PLC). SETTING: Single-site out-patient
treatment research clinic in Houston, TX, USA. PARTICIPANTS: Thirty treatment
seeking adults, 18 to 60 years old, with CUD. Eighteen participants (8 = PIO; 10
= PLC) completed diffusion tensor imaging (DTI) of WM integrity at pre-/post
treatment. INTERVENTION: Study medication was dispensed at thrice weekly visits
along with once-weekly cognitive behavioral therapy for 12 weeks. MEASUREMENTS:
Measures of target engagement mechanisms of interest included cocaine craving
assessed by the Brief Substance Craving Scale (BSCS), the Obsessive Compulsive
Drug Use Scale (OCDUS), a visual analog scale (VAS) and change in WM integrity.
Feasibility measures included number completing treatment, medication compliance
(riboflavin detection) and tolerability (side effects, serious adverse events).
FINDINGS: Target engagement change in mechanisms of interest, defined as a >=
0.75 Bayesian posterior probability of an interaction existing favoring PIO over
PLC, was demonstrated on measures of craving (BSCS, VAS) and WM integrity indexed
by fractional anisotropy (FA) values. Outcomes indicated greater decrease in
craving and greater increase in FA values in the PIO group. Feasibility was
demonstrated by high completion rates among those starting treatment (21/26 =
80%) and medication compliance (>= 80%). There were no reported serious adverse
events for PIO. CONCLUSIONS: Compared with placebo, patients receiving
pioglitazone show a higher likelihood of reduced cocaine craving and improved
brain white matter integrity as a function of time in treatment. Pioglitazone
shows good feasibility as a treatment for cocaine use disorder.
PMID- 28498504
TI - Varenicline versus nicotine patch with brief advice for smokers with substance
use disorders with or without depression: effects on smoking, substance use and
depressive symptoms.
AB - AIMS: Varenicline was compared with transdermal nicotine (NRT) for smokers with
current substance use disorders (SUD) for effects on 3-month smoking abstinence
(primary outcome) and, secondarily, on 3- and 6 month abstinence while adjusting
for medication adherence, and on additional smoking and substance use outcomes.
Moderation by major depressive disorder history (MDD) and adherence were
investigated. DESIGN: Double-blind double-placebo-controlled randomized design,
stratifying by MDD, gender and nicotine dependence, with 3 and 6 months follow
up. SETTING: University offices in Rhode Island, USA. PARTICIPANTS: Adult smokers
(n = 137), in SUD treatment, substance abstinent <12 months (n = 77 varenicline,
60 NRT). INTERVENTION AND COMPARATOR: Twelve weeks of varenicline (2 mg/day,
after 1-week dose run-up) or NRT (21 mg/day decreasing to 7 mg/day).
MEASUREMENTS: Primary: point-prevalence smoking abstinence (7-day, confirmed) at
3 months. Secondary: point-prevalence abstinence at 6 months, quantity and
frequency of smoking and substance use at 3 and 6 months, and within-treatment
abstinence, medication adherence and depressive symptoms. Smoking outcome
analyses were repeated controlling for adherence and investigating adherence as a
moderator. FINDINGS: Effects on 3-month abstinence were P < 0.065 without a
covariate (Bayes factor 3.35, supporting the effect strongly) and differed
significantly when controlling for baseline smoking [varenicline: 13%, NRT: 3%;
odds ratio (OR) = 4.81, 95% confidence interval (CI) 1.00, 23.13, P < 0.05]. The
threefold difference at 6 months was not significant. Medication effect on
abstinence across time was significant (P < 0.05) covarying adherence and
baseline smoking (OR = 6.40, 95% CI = 1.00, 40.93). Medication differences in 3
month abstinence occurred among participants with >= 77% adherence (P < 0.02). No
significant medication effects on heavy drinking, drug use or depressive symptoms
were found. CONCLUSIONS: Varenicline appears to improve the chances of achieving
at least 3 months of smoking abstinence in smokers with substance use disorders
trying to stop, compared with transdermal nicotine patches, the effect being
independent of history of depressive disorder.
PMID- 28498503
TI - p62/SQSTM1 as an oncotarget mediates cisplatin resistance through activating RIP1
NF-kappaB pathway in human ovarian cancer cells.
AB - Platinum-based therapeutic strategies have been widely used in ovarian cancer
treatment. However, drug resistance has greatly limited therapeutic efficacy.
Recently, tolerance to cisplatin has been attributed to other factors unrelated
to DNA. p62 (also known as SQSTM1) functions as a multifunctional hub
participating in tumorigenesis and may be a therapeutic target. Our previous
study showed that p62 was overexpressed in drug-resistant ovarian epithelial
carcinoma and its inhibition increased the sensitivity to cisplatin. In this
study, we demonstrate that the activity of the NF-kappaB signaling pathway and
K63-linked ubiquitination of RIP1 was higher in cisplatin-resistant ovarian
(SKOV3/DDP) cells compared with parental cells. In addition, cisplatin resistance
could be reversed by inhibiting the expression of p62 using siRNA. Furthermore,
deletion of the ZZ domain of p62 that interacts with RIP1 in SKOV3 cells markedly
decreased K63-linked ubiquitination of RIP1 and inhibited the activation of the
NF-kappaB signaling pathway. Moreover, loss of the ZZ domain from p62 led to poor
proliferative capacity and high levels of apoptosis in SKOV3 cells and made them
more sensitive to cisplatin treatment. Collectively, we provide evidence that p62
is implicated in the activation of NF-kappaB signaling that is partly dependent
on RIP1. p62 promotes cell proliferation and inhibits apoptosis thus mediating
drug resistance in ovarian cancer cells.
PMID- 28498505
TI - Autosomal dominant frontometaphyseal dysplasia: Delineation of the clinical
phenotype.
AB - Frontometaphyseal dysplasia (FMD) is caused by gain-of-function mutations in the
X-linked gene FLNA in approximately 50% of patients. Recently we characterized an
autosomal dominant form of FMD (AD-FMD) caused by mutations in MAP3K7, which
accounts for the condition in the majority of patients who lack a FLNA mutation.
We previously also described a patient with a de novo variant in TAB2, which we
hypothesized was causative of another form of AD-FMD. In this study, a cohort of
20 individuals with AD-FMD is clinically evaluated. This cohort consists of 15
individuals with the recently described, recurrent mutation (c.1454C>T) in
MAP3K7, as well as three individuals with missense mutations that result in
substitutions in the N-terminal kinase domain of TGFbeta-activated kinase 1
(TAK1), encoded by MAP3K7. Additionally, two individuals have missense variants
in the gene TAB2, which encodes a protein with a close functional relationship to
TAK1, TAK1-associated binding protein 2 (TAB2). Although the X-linked and
autosomal dominant forms of FMD are very similar, there are distinctions to be
made between the two conditions. Individuals with AD-FMD have characteristic
facial features, and are more likely to be deaf, have scoliosis and cervical
fusions, and have a cleft palate. Furthermore, there are features only found in
AD-FMD in our review of the literature including valgus deformity of the feet and
predisposition to keloid scarring. Finally, intellectual disability is present in
a small number of subjects with AD-FMD but has not been described in association
with X-linked FMD.
PMID- 28498506
TI - A Novel Pregabalin Functionalized Salicylaldehyde Derivative Afforded Prospective
Pain, Inflammation, and Pyrexia Alleviating Propensities.
AB - A novel pregabalin derivative named as pregsal ((S,E)-3-(((2
hydroxybenzylidene)amino)methyl)-5-methylhexanoic acid) was synthesized by a
simple imination reaction between pregabalin and salicylaldehyde and was
evaluated in the in vivo testing paradigms. The compound was characterized by UV,
IR, 1 H, 13 C NMR, HR ESI-MS, and elemental analysis. It was screened (30, 50,
75, and 100 mg/kg) for antinociceptive, anti-inflammatory, and antipyretic
activities in relation to pregabalin. The synthesized compound significantly
attenuated the tonic acetic acid-induced nociceptive pain (30 mg/kg (P < 0.05),
50 mg/kg (P < 0.01), 75 and 100 mg/kg (P < 0.001)), and thermal-induced
hyperalgesia (P < 0.001). These activities were succinctly antagonized (P < 0.05,
P < 0.01, P < 0.001) by naloxone and pentylenetetrazole, implicating the
involvement of opioidergic and GABAergic mechanisms. The compound also inhibited
the temporal inflammatory response and alleviated the yeast-induced pyrexia (P <
0.05, P < 0.01, and P < 0.001). These findings suggest that the synthesized
compound possessed prospective pain, inflammation, and pyrexia relieving
propensities and therefore may serve as a potential drug candidate for the
therapeutic management of chronic pain conditions.
PMID- 28498507
TI - Effect of surgical periodontal treatment associated to antimicrobial photodynamic
therapy on chronic periodontitis: A randomized controlled clinical trial.
AB - AIM: This randomized controlled clinical trial evaluated the effects of an
adjunctive single application of antimicrobial photodynamic therapy (aPDT) in
Surgical Periodontal Treatment (ST) in patients with severe chronic periodontitis
(SCP). MATERIAL AND METHODS: In a split-mouth design, 20 patients with SCP were
treated with aPDT+ST (Test Group, TG) or ST only (Control Group, CG). aPDT was
applied in a single episode, using a diode laser and a phenothiazine
photosensitizer. All patients were monitored until 90 days after surgical
therapy. Levels of 40 subgingival species were measured by checkerboard DNA-DNA
hybridization at baseline, 60 and 150 days. Clinical and microbiological
parameters were evaluated. RESULTS: In deep periodontal pockets depth (PPD >=5
mm), Test Group presented a significantly higher decrease in PPD than Control
Group at 90 days after surgical therapy (p < .05). Test Group also demonstrated
significantly less periodontal pathogens of red complex (Treponema denticola) (p
< .05). CONCLUSION: A single episode of aPDT used in adjunct to open flap
debridement of the root surface in the surgical treatment of SCP: i)
significantly improved clinical periodontal parameters; ii) eliminates
periodontal pathogens of the red complex more effectively (NCT02734784).
PMID- 28498508
TI - Stroke in Women: Risk Factors and Clinical Biomarkers.
AB - Stroke has been emerged as one of major health problems for women worldwide.
Increasing of knowledge in this field has provided new data in this area which
contribute to finding of new risk factors and could improve stroke treatment. A
large number studies indicated a variety of risk factors including sex, age,
race, smoking, diabetes, and physical inactivity could be involved in stroke in
women. The understanding of various aspects involved in women stroke including
risk factors, outcomes, stroke recovery, and prevention could provide new
therapeutic platforms which could likely lead to better treatment in women
stroke. Diagnosis is one of important steps in stroke therapy. It has been showed
that a variety of biomarkers such as microRNAs (miRNAs), tPA, and von willebrand
factor could be used as therapeutic and diagnostic biomarkers in stroke therapy.
Here, we summarized various aspects of stroke in women which could help to
recognition risk factors, outcomes, care, treatment, and novel biomarkers involve
in treatment of stroke. J. Cell. Biochem. 118: 4191-4202, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28498509
TI - Molecular interplays in hepatic stellate cells: apoptosis, senescence, and
phenotype reversion as cellular connections that modulate liver fibrosis.
AB - Liver fibrosis is a pathophysiological process correlated with intense repair and
cicatrization mechanisms in injured liver, and over the past few years, the
characterization of the fine-tuning of molecular interconnections that support
the development of liver fibrosis has been investigated. In this cellular
process, the hepatic stellate cells (HSCs) support the organ fibrogenesis. The
HSCs are found in two distinct morpho-physiological states: quiescent and
activated. In normal liver, most HSCs are found in quiescent state, presenting a
considerable amount of lipid droplets in the cytoplasm, while in injured liver,
the activated phenotype of HSCs is a myofibroblast, that secrete extracellular
matrix elements and contribute to the establishment of the fibrotic process.
Studies on the molecular mechanisms by which HSCs try to restore their quiescent
state have been performed; however, no effective treatment to reverse fibrosis
has been so far prescribed. Therefore, the elucidation of the cellular and
molecular mechanisms of apoptosis, senescence, and the cell reversion phenotype
process from activate to quiescent state will certainly contribute to the
development of effective therapies to treat hepatic fibrosis. In this context,
this review aimed to address central elements of apoptosis, senescence, and
reversal of HSC phenotype in the control of hepatic fibrogenesis, as a guide to
future development of therapeutic strategies.
PMID- 28498510
TI - Semiautomated registration of pre- and intraoperative CT for image-guided
percutaneous liver tumor ablation interventions.
AB - PURPOSE: In CT-guided liver tumor ablation interventions, registration of a
preoperative contrast-enhanced CT image to the intraoperative CT image is
hypothesized to improve guidance. This is a highly challenging registration task
due to differences in patient poses and large deformations, and therefore high
registration errors are expected. In this study, our objective is to develop a
method that enables users to locally improve the registration where the
registration fails, with minimal user interaction. METHODS: The method is based
on a conventional nonrigid intensity-based registration framework, extended with
a novel point-to-surface penalty. The point-to-surface penalty serves to improve
the alignment of the liver boundary, while requiring minimal user interaction
during the intervention: annotating some points on the liver surface at those
regions where the conventional registration seems inaccurate. RESULTS: The method
is evaluated on 18 clinical datasets. It improves registration accuracy compared
with the conventional nonrigid registration in terms of average surface distance
(from 2.75 to 2.05 mm) and target registration error (from 6.92 to 5.8 mm).
CONCLUSIONS: In this study, we introduce a semiautomated registration algorithm
that improves the accuracy of image registration.
PMID- 28498511
TI - Enhanced antitumor effect of targeted nanoliposomal bleomycin.
AB - Folate receptor (FR)-mediated drug delivery is a promising approach for active
targeting of drugs to the FR-positive tumor cells. Bleomycin (BLM) is an
antitumor antibiotic with poor therapeutic activity as a result of its limited
diffusion into tumor cells. The aim of this study was to investigate whether FR
targeted PEGylated nanoliposomes (FPNL) can effectively deliver BLM to tumor
cells and enhance its in vitro and in vivo efficacy. FPNL and PNL (non-targeted)
were prepared by thin film hydration method, and their physiochemical properties,
cellular uptake, tissue distribution and tumor inhibitory effects were
investigated. In Lewis lung cancer (LLC1) cells, FPNL containing BLM showed 2.38
fold and 3.26-fold higher cytotoxicity compared to PNL-BLM and free BLM,
respectively. Moreover, the uptake of FPNL by these cells was increased as
compared to the PNL. Furthermore, FPNL showed significantly higher tumor
distribution of BLM in the LLC1 cells and more tumor inhibition efficacy compared
to free BLM and PNL. Both formulations of nanoliposomes had longer plasma half
life than that of free BLM. Therefore, FPNL may be suitable carriers for targeted
drug delivery to FR-positive tumor cells.
PMID- 28498512
TI - Recurrent ATP2A2 p.(Pro602Leu) mutation differentiates Acrokeratosis
verruciformis of Hopf from the allelic condition Darier disease.
AB - Darier disease and Acrokeratosis Verruciformis of Hopf (AKV) are rare disorders
of keratinization with autosomal dominant inheritance and very distinct clinical
pictures. Both have been shown to be caused by mutations in ATP2A2 (ATPase, Ca++
transporting, cardiac muscle, slow-twitch) a gene encoding one of the SERCA
(sarcoplasmic/endoplasmic reticulum calcium ATPase2) intracellular pumps with a
crucial role in cell-to-cell adhesion in both skin and heart. While hundreds of
different missense and nonsense mutations cause Darier disease, only one missense
mutation, p.(Pro602Leu), has been identified in families with AKV. We report a
family with AKV due to the p.(Pro602Leu) mutation and discuss implications for
this recurrent mutation on knowledge of ATP2A2 structure and function.
PMID- 28498513
TI - Suberoylanilide hydroxamic acid sensitizes neuroblastoma to paclitaxel by
inhibiting thioredoxin-related protein 14-mediated autophagy.
AB - Paclitaxel is not as effective for neuroblastoma as most of the front-line
chemotherapeutics due to drug resistance. This study explored the regulatory
mechanism of paclitaxel-associated autophagy and potential solutions to
paclitaxel resistance in neuroblastoma. The formation of autophagic vesicles was
detected by scanning transmission electron microscopy and flow cytometry. The
autophagy-associated proteins were assessed by western blot. Autophagy was
induced and the autophagy-associated proteins LC3-I, LC3-II, Beclin 1, and
thioredoxin-related protein 14 (TRP14), were found to be upregulated in
neuroblastoma cells that were exposed to paclitaxel. The inhibition of Beclin 1
or TRP14 by siRNA increased the sensitivity of the tumor cells to paclitaxel. In
addition, Beclin 1-mediated autophagy was regulated by TRP14. Furthermore, the
TRP14 inhibitor suberoylanilide hydroxamic acid (SAHA) downregulated paclitaxel
induced autophagy and enhanced the anticancer effects of paclitaxel in normal
control cancer cells but not in cells with upregulated Beclin 1 and TRP14
expression. Our findings showed that paclitaxel-induced autophagy in
neuroblastoma cells was regulated by TRP14 and that SAHA could sensitize
neuroblastoma cells to paclitaxel by specifically inhibiting TRP14.
PMID- 28498514
TI - Secukinumab re-initiation achieves regain of high response levels in patients who
interrupt treatment for moderate to severe plaque psoriasis.
PMID- 28498515
TI - Brain Structure Linking Delay Discounting and Academic Performance.
AB - As a component of self-discipline, delay discounting refers to the ability to
wait longer for preferred rewards and plays a pivotal role in shaping students'
academic performance. However, the neural basis of the association between delay
discounting and academic performance remains largely unknown. Here, we examined
the neuroanatomical substrates underlying delay discounting and academic
performance in 214 adolescents via voxel-based morphometry (VBM) by performing
structural magnetic resonance imaging (S-MRI). Behaviorally, we confirmed the
significant correlation between delay discounting and academic performance.
Neurally, whole-brain regression analyses indicated that regional gray matter
volume (rGMV) of the left dorsolateral prefrontal cortex (DLPFC) was associated
with both delay discounting and academic performance. Furthermore, delay
discounting partly accounted for the association between academic performance and
brain structure. Differences in the rGMV of the left DLPFC related to academic
performance explained over one-third of the impact of delay discounting on
academic performance. Overall, these results provide the first evidence for the
common neural basis linking delay discounting and academic performance. Hum Brain
Mapp 38:3917-3926, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28498516
TI - Nontopotactic Reaction in Highly Reversible Sodium Storage of Ultrathin Co9 Se8
/rGO Hybrid Nanosheets.
AB - Transition metal chalcogenide with tailored nanosheet architectures with reduced
graphene oxide (rGO) for high performance electrochemical sodium ion batteries
(SIBs) are presented. Via one-step oriented attachment growth, a facile synthesis
of Co9 Se8 nanosheets anchored on rGO matrix nanocomposites is demonstrated. As
effective anode materials of SIBs, Co9 Se8 /rGO nanocomposites can deliver a
highly reversible capacity of 406 mA h g-1 at a current density of 50 mA g-1 with
long cycle stability. It can also deliver a high specific capacity of 295 mA h g
1 at a high current density of 5 A g-1 indicating its high rate capability.
Furthermore, ex situ transmission electron microscopy observations provide
insight into the reaction path of nontopotactic conversion in the hybrid anode,
revealing the highly reversible conversion directly between the hybrid Co9 Se8
/rGO and Co nanoparticles/Na2 Se matrix during the sodiation/desodiation process.
In addition, it is experimentally demonstrated that rGO plays significant roles
in both controllable growth and electrochemical conversion processes, which can
not only modulate the morphology of the product but also tune the sodium storage
performance. The investigation on hybrid Co9 Se8 /rGO nanosheets as SIBs anode
may shed light on designing new metal chalcogenide materials for high energy
storage system.
PMID- 28498517
TI - Health utility reporting in chronic rhinosinusitis patients.
AB - OBJECTIVES: Direct comparison of different diseases allows clinicians and
researchers to place the burden of symptoms and impact on quality of life of each
condition in context. Generic health-related quality-of-life assessment tools
allow such analysis, and limited data are available for British patients with
chronic rhinosinusitis. DESIGN: As part of a larger feasibility study, patients
underwent baseline assessment using the SNOT-22, SF-12 and EQ-5D-5L tools. Data
were analysed using Microsoft Excel and algorithms available for the analysis of
the later two tools. We plotted EQ-5D-5L VAS and utility scores and SF-12 MCS and
PCS scores separately against SNOT-22 scores and quantified associations using
bivariate ordinary least squares regression analysis. SETTING: Patients were
prospectively recruited from six UK outpatient clinics. PARTICIPANTS: Adult
patients with chronic rhinosinusitis without nasal polyps (CRSsNPs). MAIN OUTCOME
MEASURES: Baseline SNOT-22, SF-12 and EQ-5D-5L scores. RESULTS: Fifty-two adults
were recruited with a mean age of 55 years, 51% were male. The mean SNOT-22 score
was 43.82. Mental and physical component scores of the SF-12 were 46.53 and 46,
respectively. Mean index score computed form the EQ-5D-5L was 0.75. Worse
(higher) SNOT-22 scores were associated with lower EQ-5D-5L VAS and utility
scores and SF-12 MCS and PCS scores. CONCLUSION: The EQ-5D-5L suggests that
British CRSsNPs patients are negatively impacted with regards to quality of life.
We found the SF-12 to be less sensitive and conclude that the EQ-5D-5L tool is a
quick and accessible method for assessing QOL in order it can be compared with
other disease states.
PMID- 28498518
TI - Geophysical Investigation of Fresh-Saline Water Interface: A Case Study from
South Punjab, Pakistan.
AB - The importance of the study of fresh-saline water incursion cannot be over
emphasized. Borehole techniques have been widely used, but they are quite
expensive, intrusive, and time consuming. The electrical resistivity method has
proved very successful in groundwater assessment. This advanced technique uses
the calculation of Dar-Zarrouk (D-Z) parameters, namely longitudinal unit
conductance, transverse unit resistance, and longitudinal resistivity has been
employed by using 50 vertical electrical sounding points to assess the
groundwater and delineate the fresh-saline water interface over 1045 km2 area of
Khanewal in Southern Punjab of Pakistan. The x-y plots and maps of D-Z parameters
were produced to establish a decipherable vision for the occurrence and
distribution of different water-bearing formations of fresh-saline water aquifers
through a complicated situation of intermixing of different resistivity ranges
for fresh-saline water bodies. This technique is useful to reduce the ambiguity
produced by the process of equivalence and suppression which cause intermixing in
differentiating fresh, brackish, and saline aquifers during interpretation. The
fresh-saline water interface is correlated very well with the previous studies of
water quality analysis carried out in Khanewal area. The results suggest that the
D-Z parameters are useful for demarcating different aquifer zones. The behavior
and pattern of D-Z parameters with respect to occurrence and distribution of
different water-bearing formations were effectively identified and delineated in
the study area.
PMID- 28498519
TI - Starting enteral nutrition with preterm single donor milk instead of formula
affects time to full enteral feeding in very low birthweight infants.
AB - AIM: This study compared the impact of using either single donor breastmilk or
formula to start enteral feeding in preterm infants, on the time to full enteral
feeding, growth and morbidity. The milk was provided by other preterm mothers.
METHODS: This was an observational prospective study, carried out from June 2012
to March 2013 at the Medical University of Vienna, Austria, on the effects of
preterm single donor milk on 133 very low birthweight infants with a birthweight
<1500 g and a gestational age <32 weeks until they were on full enteral feeding.
They were compared to a retrospective group of 150 infants from March 2011 to May
2012 who received preterm formula. RESULTS: The time to full enteral feeding,
defined as 140 mL/kg, was significantly shorter in the donor milk group than in
the formula group (18 vs. 22 days, p = 0.01). Feeding donor milk was also
associated with a lower incidence for retinopathy of prematurity (4% vs. 13%, p <
0.01) and culture-proven sepsis (11% vs. 23%, p < 0.01). CONCLUSION: Feeding
preterm infants breastmilk from a single donor rather using formula was
associated with a shorter time to full enteral feeding and lower incidences of
retinopathy of prematurity and sepsis.
PMID- 28498520
TI - Gold nanoparticles-conjugated quercetin induces apoptosis via inhibition of
EGFR/PI3K/Akt-mediated pathway in breast cancer cell lines (MCF-7 and MDA-MB
231).
AB - Epidermal growth factor plays a major role in breast cancer cell proliferation,
survival, and metastasis. Quercetin, a bioactive flavonoid, is shown to exhibit
anticarcinogenic effects against various cancers including breast cancer. Hence,
the present study was designed to evaluate the effects of gold nanoparticles
conjugated quercetin (AuNPs-Qu-5) in MCF-7 and MDA-MB-231 breast cancer cell
lines. Borohydride reduced AuNPs were synthesized and conjugated with quercetin
to yield AuNPs-Qu-5. Both were thoroughly characterized by several
physicochemical techniques, and their cytotoxic effects were assessed by MTT
assay. Apoptotic studies such as DAPI, AO/EtBr dual staining, and annexin V-FITC
staining were performed. AuNPs and AuNPs-Qu-5 were spherical with crystalline
nature, and the size of particles range from 3.0 to 4.5 nm. AuNPs-Qu-5 exhibited
lower IC50 value compared to free Qu. There was a considerable increase in
apoptotic population with increased nuclear condensation seen upon treatment with
AuNPs-Qu-5. To delineate the molecular mechanism behind its apoptotic role, we
analysed the proteins involved in apoptosis and epidermal growth factor receptor
(EGFR)-mediated PI3K/Akt/GSK-3beta signalling by immunoblotting and
immunocytochemistry. The pro-apoptotic proteins (Bax, Caspase-3) were found to be
up regulated and anti-apoptotic protein (Bcl-2) was down regulated on treatment
with AuNPs-Qu-5. Additionally, AuNPs-Qu-5 treatment inhibited the EGFR and its
downstream signalling molecules PI3K/Akt/mTOR/GSK-3beta. In conclusion,
administration of AuNPs-Qu-5 in breast cancer cell lines curtails cell
proliferation through induction of apoptosis and also suppresses EGFR signalling.
AuNPs-Qu-5 is more potent than free quercetin in causing cancer cell death, and
hence, this could be a potential drug delivery system in breast cancer therapy.
PMID- 28498521
TI - Does drought stress modify the effects of plant-growth promoting rhizobacteria on
an aboveground chewing herbivore?
AB - Soil microbes have important effects on the interactions of plants with their
environment, by promoting plant growth, inducing resistance to pests or by
conferring tolerance to abiotic stress. However, their effects are variable and
the factors responsible for this variation are mainly unknown. Our aim was to
assess how drought stress modifies the effect of the nonpathogenic rhizobacterium
Pseudomonas simiae WCS417r on plant growth and resistance against the generalist
leaf-chewing caterpillar Mamestra brassicae. We studied Arabidopsis thaliana Col
0 plants, as well as mutants altered in the biosynthesis of the phytohormones
jasmonic acid (JA) and abscisic acid (ABA). Caterpillars did not prefer
rhizobacteria-treated plants, independently of drought stress. Rhizobacteria
colonization had a variable effect on caterpillar performance, which ranged from
positive in one experiment to neutral in a second one. Drought had a consistent
negative effect on herbivore performance; however, it did not modify the effect
of rhizobacteria on herbivore performance. The effect of drought on herbivore
performance was JA-mediated (confirmed with the use of the dde2-2 mutant), but it
was still present in the ABA-deficient mutant aba2-1. Plant biomass was reduced
by both drought and herbivory but it was enhanced by rhizobacterial colonization.
Pseudomonas simiae WCS417r is able to promote plant growth even when plants are
suffering herbivory. Nevertheless, the microbial effect on the herbivore is
variable, independently of drought stress. To get the best possible outcome from
the rhizobacteria-plant mutualism it is important to understand which other
factors may be responsible for its context-dependency.
PMID- 28498522
TI - Improving quality outcomes in head and neck free flap surgery with the use of a
physician inpatient coordinator.
AB - OBJECTIVES/HYPOTHESIS: Head and neck free flap patients require complex
postoperative care. The quality of care for these patients often depends on their
management from the time they leave the operating room. The purpose of this study
was to investigate the impact of a postoperative inpatient coordinator (IC) for
head and free flap patients on quality outcomes: length of stay (LOS), 30-day
unplanned return to the emergency department (30dRED), 30-day unplanned
readmissions (30dUR), and complication rates. STUDY DESIGN: Retrospective cohort
study. METHODS: One hundred eighty-eight consecutive patients who underwent head
and neck free flap surgery between January 2012 and January 2016 were reviewed
using a prospective database. Patients had an IC for their entire hospitalization
(group 1) or for less than their entire hospitalization (group 2). Logistic
regression analysis was performed to identify risk factors for quality outcomes.
RESULTS: Mean LOS was 13.8 days and 17.3 days in groups 1 and 2, respectively (P
= .002). The 30dRED rate was 12% and 22%, respectively (P = .04). Group 2 had an
increased LOS by 4.1 days (P = .001) and a 2.4 fold increased 30dRED (P = .03).
30dUR and complications were not influenced by the IC (P > .05). CONCLUSIONS: An
IC may help decrease LOS and 30dRED in head and neck free flap patients. LEVEL OF
EVIDENCE: 4. Laryngoscope, 128:336-342, 2018.
PMID- 28498523
TI - Effects of chemical management for invasive plants on the performance of
Lithobates pipiens tadpoles.
AB - Invasive plants impact amphibians by altering habitat, altering species
interactions, and releasing potentially toxic secondary chemicals. Despite being
costly and having the potential to affect nontarget wildlife, chemical management
is commonly used to control invasive plants. Prior research has indicated that
individual effects of invasive plants or herbicides can be harmful to aquatic
organisms; however, information is lacking on the combined effect of these
factors on amphibians. A laboratory experiment was performed to assess the impact
of leachates of the invasive plants Eurasian watermilfoil (Myriophyllum spicatum)
and European buckthorn (Rhamnus cathartica), the herbicide Renovate(r) 3
(triclopyr [3, 5, 6-trichloro-2-pyridinyloxyacetic acid]), and the combined
effects of each plant leachate and the herbicide on the growth, morphology, and
survival of northern leopard frog (Lithobates pipiens) tadpoles. No effects of
treatment on survival were observed. Tadpole exposure to M. spicatum reduced body
mass by 17%, exposure to R. cathartica increased body mass by 36%, and exposure
to R. cathartica + low herbicide increased body mass by 38% (although only early
in the experiment). Exposure to Renovate 3 induced a 16% and 29% decrease in
tadpole size in lower (0.22 mg triclopyr active ingredient [a.i.]/L) and higher
(0.92 mg triclopyr a.i./L) concentration treatments, respectively. Results from
the present study highlight the importance of considering both individual and
combined effects of invasive plants and herbicides because they may have
different outcomes for tadpole growth and development. Environ Toxicol Chem
2017;36:2958-2964. (c) 2017 SETAC.
PMID- 28498524
TI - Patterns of chronic hand eczema: a semantic map analysis of the CARPE registry
data.
AB - BACKGROUND: Hand eczema has a high incidence and prevalence and has a negative
impact on both physical and psychological well-being, with the risk of
persistence as a chronic condition. Epidemiological studies on hand eczema
provided mainly descriptive and risk analyses, but pattern analyses of variables
associated with hand eczema, in particular chronic hand eczema, have not been
explored to date. OBJECTIVES: To investigate and display the semantics of
associations between variables of hand eczema obtained from the Swiss and German
registries of chronic hand eczema (CARPE) to dissect patterns and novel links.
METHODS: This was a cross-sectional study on selected variables from the CARPE
registries. Associations between variables were analysed by means of an
autoassociative system. A semantic connectivity map was generated by using a
maximum spanning tree algorithm. RESULTS: Baseline datasets of 1466 patients with
chronic hand eczema (Switzerland: 199; Germany: 1267) were analysed. Occupational
exposure had the highest impact in the total and country cohorts. We identified
two areas of exposure linked to corresponding occupations that clearly demarcated
the sexes. CONCLUSIONS: This study, using semantic connectivity as a novel method
of data analysis, reveals the complexity of features characterizing chronic hand
eczema as well as novel association patterns that deserve further investigation.
PMID- 28498526
TI - The Role of Mothers' Communication in Promoting Motivation for Math and Science
Course-Taking in High School.
AB - In the context of concerns about American youths' failure to take advanced math
and science (MS) courses in high school, we examined mothers' communication with
their adolescent about taking MS courses. At ninth grade, U.S. mothers (n = 130)
were interviewed about their responses to hypothetical questions from their
adolescent about the usefulness of algebra, geometry, calculus, biology,
chemistry, and physics. Responses were coded for elaboration and making personal
connections to the adolescent. The number of science, technology, engineering,
and mathematics courses taken in 12th grade was obtained from school records.
Mothers' use of personal connections predicted adolescents' MS interest and
utility value, as well as actual MS course-taking. Parents can play an important
role in motivating their adolescent to take MS courses.
PMID- 28498527
TI - Adolescent Conflict Appraisals Moderate the Link Between Marital Conflict and
Physiological Stress Reactivity.
AB - The goal of this study was to advance understanding of how adolescent conflict
appraisals contribute uniquely, and in combination with interparental conflict
behavior, to individual differences in adolescent physiological reactivity.
Saliva samples were collected from 153 adolescents (52% female; ages 10-17 years)
before and after the Trier Social Stress Test. Saliva was assayed for cortisol
and alpha-amylase. Results revealed interactive effects between marital conflict
and conflict appraisals. For youth who appraised parental conflict negatively
(particularly as threatening), negative marital conflict predicted dampened
reactivity; for youth who appraised parental conflict less negatively, negative
marital conflict predicted heightened reactivity. These findings support the
notion that the family context and youth appraisals of family relationships are
linked with individual differences in biological sensitivity to context.
PMID- 28498525
TI - The Shared Etiology of Attentional Control and Anxiety: An Adolescent Twin Study.
AB - We investigated the etiology of attentional control (AC) and four different
anxiety symptom types (generalized, obsessive-compulsive, separation, and social)
in an adolescent sample of over 400 twin pairs. Genetic factors contributed to
55% of the variance in AC and between 43 and 58% of the variance in anxiety.
Negative phenotypic associations between AC and anxiety indicated that lower
attentional ability is related to increased risk for all 4 anxiety categories.
Genetic correlations between AC and anxiety phenotypes ranged from -.36 to -.47,
with evidence of nonshared environmental covariance between AC and generalized
and separation anxiety. Results suggest that AC is a phenotypic and genetic risk
factor for anxiety in early adolescence, with somewhat differing levels of risk
depending on symptomatology.
PMID- 28498528
TI - Family, Peer, and Pubertal Determinants of Dating Involvement Among Adolescents.
AB - This study examines the influence of family, peer, and biological contributors to
dating involvement among early adolescents (11-14 years of age; n = 244).
Further, we assess how parental monitoring may be modified by pubertal maturation
and older sibling risky behavior. Data on delinquent peer affiliation, pubertal
maturation, parental monitoring, older sibling risky behavior, and dating
involvement were gathered through observations and surveys from adolescents,
mothers, older siblings, and teachers. Results indicate that lower levels of
parental monitoring and higher levels of older sibling risky behavior were
related to adolescents' dating involvement through delinquent peer affiliation.
Pubertal maturation was directly related to dating involvement for early daters.
Findings emphasize the value of examining social and biological factors, in
concert, over time.
PMID- 28498529
TI - Mother-Adolescent Proficiency in a Common Language Facilitates Socialization
Among Mexican-Origin Families.
AB - The primary goal of this study was to test how mother and adolescent proficiency
in a common language moderates the link from parenting to adolescent development.
A sample of Mexican-origin fifth-grade adolescents (N = 674, 50% female) was
measured longitudinally on self-control and aggression. Mothers were rated on
observed positive discipline, warmth, and harsh discipline. Positive discipline
and warm parenting predicted increases in self-control and decreases in
aggression, but only among mother-adolescent dyads who were proficient in a
common language. Harsh parenting predicted decreases in self-control and
increases in aggression, but only among dyads who were not proficient in a common
language. Similar results were found in a conceptual replication among a second
sample of 167 Mexican-origin adolescents.
PMID- 28498530
TI - Examining Discrimination, Ethnic-Racial Identity Status, and Youth Public Regard
Among Black, Latino, and White Adolescents.
AB - How positively adolescents believe others feel about their ethnic-racial group
(i.e., public regard) is an important part of their ethnic-racial identity (ERI),
which is likely informed by contextual and individual factors. Using cluster
analyses to generate ERI statuses among Black, Latino, and White adolescents (n =
1,378), we found that associations between peer versus adult discrimination and
public regard varied across ERI status and ethnic-racial group. However, among
all adolescents, an achieved ERI (i.e., having explored ethnicity-race and having
a clear sense about its personal meaning) buffered the negative association
between adult discrimination and public regard, but not between peer
discrimination and public regard. Implications for understanding the interplay
between contextual and individual factors for public regard are discussed.
PMID- 28498532
TI - The Impact of Adolescents' Classroom and Neighborhood Ethnic Diversity on Same-
and Cross-Ethnic Friendships Within Classrooms.
AB - This study examines how classroom and neighborhood ethnic diversity affect
adolescents' tendency to form same- versus cross-ethnic friendships when they
enter middle school. Hypotheses are derived from exposure, conflict, and
constrict theory. Hypotheses are tested among 911 middle school students (43
classrooms, nine schools) in the Netherlands. Multilevel (p2) social network
analyses show that students were more likely to engage in same-ethnic rather than
cross-ethnic friendships. In line with conflict theory, greater classroom and
neighborhood diversity were related to stronger tendencies to choose same-ethnic
rather than cross-ethnic friends, among both ethnic majority and minority
students. Diversity did not hamper reciprocity, as students in more ethnically
diverse classrooms were even more likely to reciprocate friendships.
PMID- 28498531
TI - Developmental Latent Patterns of Identification as Mostly Heterosexual Versus
Lesbian, Gay, or Bisexual.
AB - Scant research exists on the development of mostly heterosexual identity, the
largest sexual orientation minority subgroup. We used longitudinal latent class
analysis to characterize the patterns of identification with lesbian, gay,
bisexual (LGB), or mostly heterosexual identities from ages 12 to 23 in 13,859
youth (57% female) in a U.S. national cohort. Three classes emerged: completely
heterosexual (88.2%), mostly heterosexual (9.5%), and LGB (2.4%). LGB class youth
generally identified with sexual minority identities by ages 12-17. In contrast,
mostly heterosexual class youth identified with sexual minority identities
gradually, with steady increases in endorsement starting at the age of 14.
Developmental implications of these differential patterns are discussed.
PMID- 28498533
TI - Modeling Trajectories of Adolescent-Perceived Family Conflict: Effects of Marital
Dissatisfaction and Parental Alcoholism.
AB - We evaluated the effects of marital dissatisfaction on adolescent-perceived
conflict in 435 families with and without a parental history of alcoholism. On
average, family conflict decreased linearly as adolescents aged. Families with an
alcoholic parent demonstrated higher adolescent-reported family conflict and this
effect was partially mediated by higher mother- and father-reported marital
dissatisfaction. Families with higher marital dissatisfaction had greater
conflict when adolescents were young (based on fathers' marital dissatisfaction)
and as they aged (based on mother's marital dissatisfaction). Years in which
mothers reported higher marital dissatisfaction than usual coincided with years
in which adolescents reported greater family conflict. Results indicate that
marital dissatisfaction has both within and between-family effects on adolescent
perceptions of conflict.
PMID- 28498534
TI - Adolescent Life Stress and the Cortisol Awakening Response: The Moderating Roles
of Attachment and Sex.
AB - This longitudinal study investigated how past versus current life stresses relate
to adolescents' cortisol awakening response (CAR), an index of hypothalamic
pituitary-adrenal activity. Ninety-nine adolescents reported previous year life
stress at ages 12 and 18. At the second assessment, participants also provided
self-reports of parent and peer attachment and 3 days of cortisol samples.
Current stress was associated with heightened CAR for both males and females,
whereas past stress was associated with attenuated CAR for males. Attachment to
peers buffered the relationship between past stress and attenuated CAR for all
adolescents; attachment to parents was a buffer for male adolescents only.
Results demonstrate the protective roles of adolescent relationships and
highlight sex differences in biopsychosocial development across adolescence.
PMID- 28498535
TI - Domain Specificity in Adolescents' Concepts of Laws: Associations Among Beliefs
and Behavior.
AB - Using detailed vignettes and scale measures, concepts of laws regulating domain
specific issues and engagement in delinquency were assessed among 340 9th through
12th graders (Mage = 16.64, SD = 1.37). Adolescents distinguished between laws
that regulate moral, drug-related prudential, conventional, personal, and
multifaceted issues in their criterion judgments and justifications. Youths'
ratings of the importance of laws, obligation to obey laws, and deserved
punishment for breaking different laws also followed domain-consistent patterns.
Adolescents' engagement in moral, drug-related prudential, and multifaceted forms
of delinquency was associated with less supportive judgments about laws within
the same domain. Findings contribute to civic development research by
demonstrating domain specificity in adolescents' beliefs about laws and suggest
that these beliefs are linked with engagement in similar types of delinquency.
PMID- 28498536
TI - Unauthorized Status and Youth Development in the United States: Consensus
Statement of the Society for Research on Adolescence.
AB - In the United States, 5.3 million children and adolescents are growing up either
with unauthorized status or with at least one parent who has that status. Until
recently, little in the way of research has informed federal, state, and local
policy debates related to unauthorized status (e.g., border enforcement,
deportation, and a pathway to citizenship) although these issues have important
implications for youth development. This statement is a brief summary of the
research evidence on multiple domains of development that may be affected by the
child or parent's unauthorized status. We also describe the contextual and
psychological mechanisms that may link this status to developmental outcomes. We
summarize a range of policies and practices that could reduce the developmental
harm to children, youth, and their families stemming from this status. Finally,
we conclude with recommendations for policy, practice, and research that are
based on the evidence reviewed.
PMID- 28498537
TI - Contagion of Anxiety Symptoms Among Adolescent Siblings: A Twin Study.
AB - This study examined whether social contagion of anxiety symptoms is present
between siblings during early adolescence and whether this process is moderated
by sex, relationship quality, and zygosity. Based on 634 monozygotic and
dizygotic twins (336 females) assessed in Grades 6 and 7, anxiety symptoms and
sibling relationship quality were measured with self-report questionnaires. The
predictive association of the co-twin's level of anxiety with adolescents' own
increased anxiety 1 year later was only observed in same-sex twin dyads
(monozygotic and dizygotic) and was higher for those who perceived a higher level
of relationship quality with their co-twin. Raising awareness of a possible
sibling contagion of anxiety may be useful for preventing the development of
anxiety symptoms in youth.
PMID- 28498538
TI - Hanging Out With the Right Crowd: Peer Influence on Risk-Taking Behavior in
Adolescence.
AB - Peer influence plays a key role in the increase of risk-taking behavior during
adolescence. However, its underlying processes are not fully understood. This
study examined the effects of social norms, conveyed through peer advice, on risk
taking behavior in 15- to 17-year-old adolescents (N = 76). Participants played a
card-guessing task alone and with online peer advice. Results showed that risk
taking increased in the presence of peers. The results further showed that
adolescents took into account the uncertainty associated with gambles, as well as
the social norms conveyed by peers. Our findings suggest that peers are most
influential in uncertain situations and demonstrate the value of a social norms
approach in examining the processes underlying peer effects.
PMID- 28498539
TI - Part-Time Employment and Problem Behaviors: Evidence From Adolescents in South
Korea.
AB - This study explores the impact of adolescent part-time work experience on problem
behaviors in the South Korean context. To achieve this, propensity score matching
(PSM) analyses were employed based on data from the Korean Education Employment
Panel (KEEP). Results indicate that adolescents' part-time employment during
their secondary school years had significantly undesirable effects on drinking
and smoking, even after preexisting differences between the two groups (i.e.,
those adolescents who participated in part-time work and those who did not) were
controlled by PSM. However, an insignificant difference was detected in the
likelihood of running away from home. Implications of the results are discussed
in terms of changes in the meanings of adolescence and of participating in part
time work in South Korea.
PMID- 28498540
TI - Patterns of Adolescent Regulatory Responses During Family Conflict and Mental
Health Trajectories.
AB - Four distinct patterns of adolescents' behavioral, emotional, and physiological
responses to family conflict were identified during mother-father-adolescent (M =
13.08 years) interactions. Most youth displayed adaptively regulated patterns
comprised of low overt and subjective distress. Under-controlled adolescents
exhibited elevated observable and subjective anger. Over-controlled adolescents
were withdrawn and reported heightened subjective distress. Physiologically
reactive adolescents had elevated cortisol coupled with low overt and subjective
distress. Regulation patterns were associated with unique mental health
trajectories. Under-controlled adolescents had elevated conduct and peer problems
whereas over-controlled adolescents had higher anxiety and depressive symptoms.
Physiologically reactive adolescents had low concurrent, but increasing levels of
depressive, anxiety, and peer problem symptoms. Findings underscore the
importance of examining organizations of regulatory strategies in contributing to
adolescent mental health.
PMID- 28498541
TI - Current data about the benefit of prehabilitation for colorectal cancer patients
undergoing surgery are not sufficient to alter the NHS cancer waiting targets.
PMID- 28498542
TI - Cloud Watching in Clinical Pathology.
PMID- 28498543
TI - Infliximab biosimilar CT-P13 in the treatment of chronic plaque psoriasis: data
from the Psobiosimilars registry.
PMID- 28498544
TI - Metabolic engineering of cofactor flavin adenine dinucleotide (FAD) synthesis and
regeneration in Escherichia coli for production of alpha-keto acids.
AB - Cofactor flavin adenine dinucleotide (FAD) plays a vital role in many FAD
dependent enzymatic reactions; therefore, how to efficiently accelerate FAD
synthesis and regeneration is an important topic in biocatalysis and metabolic
engineering. In this study, a system involving the synthesis pathway and
regeneration of FAD was engineered in Escherichia coli to improve alpha-keto acid
production-from the corresponding l-amino acids-catalyzed by FAD-dependent l
amino acid deaminase (l-AAD). First, key genes, ribH, ribC, and ribF, were
overexpressed and fine-tuned for FAD synthesis. In the resulting E. coli strain
PHCF7, strong overexpression of pma, ribC, and ribF and moderate overexpression
of ribH yielded a 90% increase in phenylpyruvic acid (PPA) titer: 19.4 +/- 1.1 g
. L-1 . Next, formate dehydrogenase (FDH) and NADH oxidase (NOX) were
overexpressed to strengthen the regeneration rate of cofactors FADH2 /FAD using
FDH for FADH2 /FAD regeneration and NOX for NAD+ /NADH regeneration. The
resulting E. coli strain PHCF7-FDH-NOX yielded the highest PPA production: 31.4
+/- 1.1 g . L-1 . Finally, this whole-cell system was adapted to production of
other alpha-keto acids including alpha-ketoglutaric acid, alpha-ketoisocaproate,
and keto-gamma-methylthiobutyric acid to demonstrate the broad utility of
strengthening of FAD synthesis and FADH2 /FAD regeneration for production of
alpha-keto acids. Notably, the strategy reported herein may be generally
applicable to other flavin-dependent biocatalysis reactions and metabolic pathway
optimizations. Biotechnol. Bioeng. 2017;114: 1928-1936. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28498545
TI - Fluorogenic Sensing of Carcinogenic Bisphenol A using Aptamer-Capped Mesoporous
Silica Nanoparticles.
AB - Mesoporous silica nanoparticles loaded with rhodamine B and capped with a
bisphenol A aptamer were used for the selective and sensitive detection of this
lethal chemical. The pores of the nanoparticles are selectively opened in the
presence of bisphenol A (through its selective coordination with the aptamer)
with subsequent rhodamine B delivery. With this capped material a limit of
detection as low as 3.5 MUm of bisphenol A was measured.
PMID- 28498546
TI - The use of inverted-L posteromedial thigh (L-PMT) flap for autologous breast
reconstruction: A case report.
AB - The posteromedial thigh (PMT) flap has been described for breast reconstruction
in vertical fashion (vPMT). However, it might not incorporate enough soft tissue
for reconstruction of a medium size breast. Here, we present a case utilizing the
free inverted-L posteromedial thigh (L-PMT) flap for autologous reconstruction of
the breast. A 65-year-old woman with a body max index (BMI) of 24.5 kg/m2
underwent nipple sparring mastectomy and received immediate unilateral breast
reconstruction. The flap was raised based on the first medial perforator of the
profunda femoris artery (PFA). The internal mammary artery and vein were
dissected as recipient vessels. The flap size was 25 cm * 25 cm. The mastectomy
specimen and weight of the flap was 260 g and 310 g, respectively. The flap
survived completely after surgery. The donor site was primarily closed with
minimal morbidities. Follow-up observations were conducted from 1 to 6 months.
The patient was satisfied with the reconstruction. The free L-PMT flap may be
suitable for breast reconstruction in women with moderate breast size. The
inverted-L pattern of the PMT flap allows the surgeon to include a bigger
quantity of flap soft tissue enabling a more anatomical shape of the breast and
represents an alternative design that may be used for autologous breast
reconstruction in selected patients.
PMID- 28498547
TI - The narcotic clinic in New Orleans, 1919-21.
AB - AIMS: This paper traces the history of the narcotic clinic in New Orleans,
Louisiana, comparing its merits to a similar clinic in Shreveport. How do the
clinics compare, and why did the Shreveport clinic operate for longer than its
New Orleans counterpart? METHODS: Qualitative analysis of contemporary medical
journals and newspapers, as well as archival materials from the Narcotic
Division. In addition, the records of Louisiana Governor John M. Parker, the
papers of Dr Willis P. Butler in Shreveport, as well as the records of the
Orleans Parish Medical Society have been utilized. FINDINGS: The narcotic clinic
in Shreveport benefited from strong local support, while the New Orleans clinic
faced a more vocal opposition. In addition, the Shreveport clinic offered a broad
array of services and was a pillar of the community; the New Orleans clinic was
newly established and offered fewer services. It was especially the influx of out
of-state addicts that angered many New Orleanians, many of whom witnessed the
addicts lined up in the French Quarter. CONCLUSION: The effectiveness of the
narcotic clinics in Louisiana (1919-23) was influenced by local opinion. The New
Orleans clinic faced a tougher political climate than its counterpart in
Shreveport, and therefore proved less resilient in the face of federal
opposition.
PMID- 28498550
TI - HBx protein-mediated ATOH1 downregulation suppresses ARID2 expression and
promotes hepatocellular carcinoma.
AB - Hepatitis B virus X protein plays a crucial role in the pathogenesis of
hepatocellular carcinoma. We previously showed that the tumor suppressor ARID2
inhibits hepatoma cell cycle progression and tumor growth. Here, we evaluated
whether hepatitis B virus X protein was involved in the modulation of ARID2
expression and hepatocarcinogenesis associated with hepatitis B virus infection.
ARID2 expression was downregulated in HBV-replicative hepatoma cells, HBV
transgenic mice, and HBV-related clinical HCC tissues. The expression levels of
HBx were negatively associated with those of ARID2 in hepatocellular carcinoma
tissues. Furthermore, HBx suppressed ARID2 at transcriptional level.
Mechanistically, the promoter region of ARID2 gene inhibited by HBx was located
at nt-1040/nt-601 and contained potential ATOH1 binding elements. In addition,
ectopic expression of ATOH1 or mutation of ATOH1 binding sites within ARID2
promoter partially abolished HBx-triggered ARID2 transcriptional repression.
Functionally, ARID2 abrogated HBx-enhanced migration and proliferation of
hepatoma cells, whereas depletion of ATOH1 enhanced tumorigenecity of HCC cells.
Therefore, our findings suggested that deregulation of ARID2 by HBx through ATOH1
may be involved in HBV-related hepatocellular carcinoma development.
PMID- 28498548
TI - Engineered 3D Cardiac Fibrotic Tissue to Study Fibrotic Remodeling.
AB - Activation of cardiac fibroblasts into myofibroblasts is considered to play an
essential role in cardiac remodeling and fibrosis. A limiting factor in studying
this process is the spontaneous activation of cardiac fibroblasts when cultured
on two-dimensional (2D) culture plates. In this study, a simplified three
dimensional (3D) hydrogel platform of contractile cardiac tissue, stimulated by
transforming growth factor-beta1 (TGF-beta1), is presented to recapitulate a
fibrogenic microenvironment. It is hypothesized that the quiescent state of
cardiac fibroblasts can be maintained by mimicking the mechanical stiffness of
native heart tissue. To test this hypothesis, a 3D cell culture model consisting
of cardiomyocytes and cardiac fibroblasts encapsulated within a mechanically
engineered gelatin methacryloyl hydrogel, is developed. The study shows that
cardiac fibroblasts maintain their quiescent phenotype in mechanically tuned
hydrogels. Additionally, treatment with a beta-adrenergic agonist increases
beating frequency, demonstrating physiologic-like behavior of the heart
constructs. Subsequently, quiescent cardiac fibroblasts within the constructs are
activated by the exogenous addition of TGF-beta1. The expression of fibrotic
protein markers (and the functional changes in mechanical stiffness) in the
fibrotic-like tissues are analyzed to validate the model. Overall, this 3D
engineered culture model of contractile cardiac tissue enables controlled
activation of cardiac fibroblasts, demonstrating the usability of this platform
to study fibrotic remodeling.
PMID- 28498551
TI - Sofosbuvir-velpatasvir with ribavirin for 24 weeks in hepatitis C virus patients
previously treated with a direct-acting antiviral regimen.
AB - : The optimal retreatment strategy for patients chronically infected with
hepatitis C virus who experience virologic failure after treatment with direct
acting antiviral-based therapies remains unclear. In this multicenter, open
label, phase 2 study, we evaluated the efficacy and safety of a fixed-dose
combination of sofosbuvir-velpatasvir (400 mg/100 mg) plus weight-adjusted
ribavirin administered for 24 weeks in patients who did not achieve sustained
virologic response after prior treatment with direct-acting antiviral regimens
that included the nucleotide analogue nonstructural protein 5B inhibitor
sofosbuvir plus the nonstructural protein 5A inhibitor velpatasvir with or
without the nonstructural protein 3/4A protease inhibitor voxilaprevir. The
primary efficacy endpoint was the proportion of patients achieving sustained
virologic response at 12 weeks after the cessation of treatment. In total, 63 of
69 (91%; 95% confidence interval, 82%-97%) patients achieved sustained virologic
response at 12 weeks, including 36 of 37 (97%; 95% confidence interval, 86%-100%)
patients with hepatitis C virus genotype 1 infection, 13 of 14 (93%; 95%
confidence interval, 66%-100%) patients with genotype 2 infection, and 14 of 18
(78%; 95% confidence interval, 52%-94%) patients with genotype 3 infection. Most
adverse events were of mild or moderate severity. The most frequently reported
adverse events were fatigue, nausea, headache, insomnia, and rash. One patient
(1%) with genotype 1a infection discontinued all study drugs due to an adverse
event (irritability). CONCLUSION: Retreatment of patients who previously failed
direct-acting antiviral-based therapies with sofosbuvir-velpatasvir plus
ribavirin for 24 weeks was well tolerated and effective, particularly those with
hepatitis C virus genotype 1 or 2 infection. (Hepatology 2017;66:1083-1089).
PMID- 28498552
TI - Ex vivo biomechanical stability of 5 cricoid-suture constructs for equine
laryngoplasty.
AB - OBJECTIVE: To determine the biomechanical properties of 5 suture constructs in
the equine cricoid under cyclic loading and load to failure testing. STUDY
DESIGN: Ex vivo study. SAMPLES: Seventy-five equine cadaver larynges. METHODS:
Each larynx was implanted with 1 of 5 cricoid-suture constructs. The standard
laryngoplasty, where a suture is passed once through the cricoid, including its
caudal edge, was used in 2 constructs: 1 with 5 USP Ethibond (ES) and 1 with 2 mm
Fibertape (FS). In the third construct, the 2 mm Fibertape was passed twice
through the cricoid including its caudal edge (Double Loop-DL). Constructs 4 and
5 used 2 mm Fibertape in a U-shaped loop passed through the cricoid but excluding
its caudal edge. One construct was supported with a metallic button (MB) on the
caudo-ventral aspect of the cricoid while the other included only the U-shaped
loop (U). Constructs were subjected to cyclic loading and to single cycle to
failure. Reduction of the left-to-right arytenoid angle quotient (LRQ), suture
migration, and load at failure were compared. RESULTS: LRQ reduction after cyclic
loading was lower in MB and U than ES constructs. During cyclic loading, suture
migration was reduced in MB, U, and DL compared to ES constructs. Mean load at
failure was lower in FS and U than in ES constructs. CONCLUSION: Loss of
abduction after equine laryngoplasty may be reduced and pullout forces increased
by applying a MB construct in the cricoid cartilage. In vivo testing is required
to verify these results.
PMID- 28498553
TI - Fundamentals of Clinical Pharmacology With Application for Pregnant Women.
AB - Medication use is common in pregnancy, yet for most medications the optimal
formulation and dosage have not been described specifically for pregnant women.
Often, adverse effects are only discovered anecdotally or after extensive off
label use occurs. Since pharmacologic research that includes pregnant women is
sparse and animal studies are often not applicable to the human fetus, providers
must use knowledge of drug behavior and normal physiologic changes of pregnancy
to personalize treatment for pregnant women. In this review, we present an
overview of the basic concepts of clinical pharmacology: pharmacokinetics,
pharmacodynamics, and pharmacogenomics. The normal physiologic changes of
pregnancy are presented as a framework to understand alterations in drug
behavior. A clinical vignette that addresses 4 pregnancy scenarios involving
medications-preterm birth, vaccination, herpes simplex virus infection, and
codeine toxicity-is provided to illustrate application of core clinical
pharmacologic concepts. Discussion of relevant literature illustrates the
challenges of offering individualized pharmacologic therapy in pregnancy.
PMID- 28498554
TI - Differential resistance to platinum-based drugs and 5-fluorouracil in p22phox
overexpressing oral squamous cell carcinoma: Implications of alternative
treatment strategies.
AB - BACKGROUND: We have previously shown that p22phox confers resistance to cisplatin
in oral squamous cell carcinoma (OSCC). Whether p22phox has clinical correlation
with cisplatin resistance and affects the efficacy of other platinum or
nonplatinum drugs is unknown. METHODS: The p22phox expression in tissues and
apoptotic markers in cell lines was detected by immunoblotting. The cytotoxicity
of chemotherapy drugs was determined by methylthiazol tetrazolium assay. In vivo
chemoresistance of p22phox-overexpressing tumors was confirmed by the xenograft
mouse model. RESULTS: The p22phox was upregulated in tumors of patients with OSCC
refractory to cisplatin treatment. The p22phox overexpression markedly increased
the resistance to cisplatin and carboplatin, but not oxaliplatin and 5
fluorouracil (5-FU), in OSCC cells by differentially inhibiting the drug-induced
apoptosis. Furthermore, p22phox-dependent resistance to cisplatin, but not 5-FU,
was demonstrated in mouse xenograft tumors. CONCLUSION: The p22phox expression
may not only be a prognostic biomarker for prediction of chemotherapy outcomes,
but the indication for alternative treatment strategies in oral cancer.
PMID- 28498555
TI - Trauma-Related Pain, Reexperiencing Symptoms, and Treatment of Posttraumatic
Stress Disorder: A Longitudinal Study of Veterans.
AB - Research has demonstrated a strong positive association between posttraumatic
stress disorder (PTSD) symptoms and physical pain. However, few studies have
explored the impact of pain problems on the symptoms and treatment of PTSD, and
results remain inconsistent. This longitudinal study examined whether trauma
related and trauma-unrelated pain differentially and uniquely predicted
reexperiencing symptoms. We also examined whether levels of reexperiencing
symptoms mediated the relationship between pain intensity and posttreatment
symptoms of avoidance, numbing, and hyperarousal (ANH). Analyses were conducted
using archival data from 99 treatment-seeking veterans who reported the etiology
and intensity of their pain and severity of PTSD symptoms pre- and posttreatment.
Among veterans with trauma-related pain, pain intensity (a) uniquely corresponded
to greater posttreatment reexperiencing symptoms (b = 1.09), and (b) was
indirectly predictive of ANH symptoms via the reexperiencing symptoms (b = 1.93).
However, veterans with trauma-unrelated pain evidenced no associations between
pain intensity and reexperiencing (b = 0.04) or ANH symptoms (b = 0.06). We thus
found that trauma-related pain was indirectly related to poor PTSD treatment
outcomes via reexperiencing symptoms. These findings offer additional insight
into factors that may influence PTSD treatment outcomes for pain-suffering trauma
survivors.
PMID- 28498556
TI - Adaptive and maladaptive functioning in Kleefstra syndrome compared to other rare
genetic disorders with intellectual disabilities.
AB - Detailed neurobehavioural profiles are of major value for specific clinical
management, but have remained underexposed in the population with intellectual
disabilities (ID). This was traditionally classified based on IQ level only.
Rapid advances in genetics enable etiology based stratification in the majority
of patients, which reduces clinical heterogeneity. This paper illustrates that
specific profiles can be obtained for rare syndromes with ID. Our main aim was to
study (mal)adaptive functioning in Kleefstra Syndrome (KS) by comparing and
contrasting our findings to three other subgroups: Koolen-de Vries Syndrome,
GATAD2B-related syndrome, and a mixed control group of individuals with ID. In
total, we studied 58 individuals (28 males, 30 females) with ID; 24 were
diagnosed with KS, 13 with Koolen-de Vries Syndrome, 6 with the GATAD2B-related
syndrome, and 15 individuals with undefined neurodevelopmental disorders. All
individuals were examined with a Vineland Adaptive Behavior Scale, mini PAS-ADD
interview, and an Autism Diagnostic Observation Schedule to obtain measures of
adaptive and maladaptive functioning. Each of the three distinctive genetic
disorders showed its own specific profile of adaptive and maladaptive
functioning, while being contrasted mutually. However, when data of the subgroups
altogether are contrasted to the data of KS, such differences could not be
demonstrated. Based on our findings, specific management recommendations were
discussed for each of the three syndromes. It is strongly suggested to consider
the genetic origin in individuals with congenital neurodevelopmental disorders
for individual based psychiatric and behavioral management.
PMID- 28498557
TI - Preparation of Ultrathin Two-Dimensional Tix Ta1-x Sy Oz Nanosheets as Highly
Efficient Photothermal Agents.
AB - Although two-dimensional (2D) metal oxide/sulfide hybrid nanostructures have been
synthesized, the facile preparation of ultrathin 2D nanosheets in high yield
still remains a challenge. Herein, we report the first high-yield preparation of
solution-processed ultrathin 2D metal oxide/sulfide hybrid nanosheets, that is,
Tix Ta1-x Sy Oz (x=0.71, 0.49, and 0.30), from Tix Ta1-x S2 precursors. The
nanosheet exhibits strong absorbance in the near-infrared region, giving a large
extinction coefficient of 54.1 L g-1 cm-1 at 808 nm, and a high photothermal
conversion efficiency of 39.2 %. After modification with lipoic acid-conjugated
polyethylene glycol, the nanosheet is a suitable photothermal agent for treatment
of cancer cells under 808 nm laser irradiation. This work provides a facile and
general method for the preparation of 2D metal oxide/sulfide hybrid nanosheets.
PMID- 28498558
TI - (E)-1,1,4,4-Tetramethyl-2-tetrazene (TMTZ): A Prospective Alternative to
Hydrazines in Rocket Propulsion.
AB - 1,1,4,4-Tetramethyl-2-tetrazene (TMTZ) is considered as a prospective replacement
for toxic hydrazines used in liquid rocket propulsion. The heat of formation of
TMTZ was computed and measured, giving values well above those of the hydrazines
commonly used in propulsion. This led to a predicted maximum Isp of 337 s for
TMTZ/N2 O4 mixtures, which is a value comparable to that of monomethylhydrazine.
We found that TMTZ has a vapor pressure well below that of liquid hydrazines, and
it is far less toxic. Finally, an improved synthesis is proposed, which is
compatible with existing industrial production facilities after minor changes.
TMTZ is thus an attractive liquid propellant candidate, with a performance
comparable to hydrazines but a lower vapor pressure and toxicity.
PMID- 28498559
TI - Altitude sickness and altitude adaptation.
PMID- 28498560
TI - Deletion of alpha5 nicotine receptor subunits abolishes nicotinic aversive
motivational effects in a manner that phenocopies dopamine receptor antagonism.
AB - Nicotine addiction is a worldwide epidemic that claims millions of lives each
year. Genetic deletion of alpha5 nicotinic acetylcholine receptor (nAChR)
subunits has been associated with increased nicotine intake, however, it remains
unclear whether acute nicotine is less aversive or more rewarding, and whether
mice lacking the alpha5 nAChR subunit can experience withdrawal from chronic
nicotine. We used place conditioning and conditioned taste avoidance paradigms to
examine the effect of alpha5 subunit-containing nAChR deletion (alpha5 -/-) on
conditioned approach and avoidance behaviour in nondependent and nicotine
dependent and -withdrawn mice, and compared these motivational effects with those
elicited after dopamine receptor antagonism. We show that nondependent alpha5 -/-
mice find low, non-motivational doses of nicotine rewarding, and do not show an
aversive conditioned response or taste avoidance to higher aversive doses of
nicotine. Furthermore, nicotine-dependent alpha5 -/- mice do not show a
conditioned aversive motivational response to withdrawal from chronic nicotine,
although they continue to exhibit a somatic withdrawal syndrome. These effects
phenocopy those observed after dopamine receptor antagonism, but are not
additive, suggesting that alpha5 nAChR subunits act in the same pathway as
dopamine and are critical for the experience of nicotine's aversive, but not
rewarding motivational effects in both a nondependent and nicotine-dependent and
withdrawn motivational state. Genetic deletion of alpha5 nAChR subunits leads to
a behavioural phenotype that exactly matches that observed after antagonizing
dopamine receptors, thus we suggest that modulation of nicotinic receptors
containing alpha5 subunits may modify dopaminergic signalling, suggesting novel
therapeutic treatments for smoking cessation.
PMID- 28498561
TI - Distinct dynamics and interaction patterns in H- and K-Ras oncogenic P-loop
mutants.
AB - Despite years of study, the structural or dynamical basis for the differential
reactivity and oncogenicity of Ras isoforms and mutants remains unclear. In this
study, we investigated the effects of amino acid variations on the structure and
dynamics of wild type and oncogenic mutants G12D, G12V, and G13D of H- and K-Ras
proteins. Based on data from us-scale molecular dynamics simulations, we show
that the overall structure of the proteins remains similar but there are
important differences in dynamics and interaction networks. We identified
differences in residue interaction patterns around the canonical switch and
distal loop regions, and persistent sodium ion binding near the GTP particularly
in the G13D mutants. Our results also suggest that different Ras variants have
distinct local structural features and interactions with the GTP, variations that
have the potential to affect GTP release and hydrolysis. Furthermore, we found
that H-Ras proteins and particularly the G12V and G13D variants are significantly
more flexible than their K-Ras counterparts. Finally, while most of the simulated
proteins sampled the effector-interacting state 2 conformational state, G12V and
G13D H-Ras adopted an open switch state 1 conformation that is defective in
effector interaction. These differences have implications for Ras GTPase
activity, effector or exchange factor binding, dimerization and membrane
interaction. Proteins 2017; 85:1618-1632. (c) 2017 Wiley Periodicals, Inc.
PMID- 28498563
TI - Identification of factors associated with treatment refractoriness of oral
lesions in pemphigus vulgaris.
AB - BACKGROUND: The oral mucosal lesions of patients with pemphigus vulgaris are
known to show more treatment refractoriness than skin lesions. OBJECTIVES: To
identify which clinical and laboratory parameters may indicate treatment
refractoriness of oral lesions in pemphigus vulgaris. METHODS: This was a
prospective study of 50 adults with pemphigus vulgaris and oral lesions; patients
were given treatment appropriate for overall disease severity. Treatment
refractoriness was defined arbitrarily as less than 75% reduction in oral
objective Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) after
treatment for 6 months. RESULTS: Of 46 patients who completed the study, 17 (37%)
were treatment refractory whereas 29 (63%) were treatment responsive. At
baseline, the treatment refractory group had a significantly longer mean duration
of disease (P = 0.02) and mean duration of oral lesions (P = 0.01), a higher
percentage of lesions in the retromolar trigone (P = 0.05) and on the occlusion
line along the buccal mucosa (P = 0.04), a higher percentage of deep/crateriform
ulcers (P < 0.001) and erosions with a lichenoid hue (P < 0.001). Herpes simplex
virus (HSV) DNA positivity, assessed by polymerase chain reaction in oral tissue
scrapings (P = 0.02), was also significantly higher in the treatment refractory
group. No other factors we tested for were statistically significant.
CONCLUSIONS: Treatment refractoriness of oral lesions was significantly
associated with duration of disease/oral lesions; specific morphology and
location of oral lesions; and the presence of HSV DNA in the oral cavity. These
factors may forewarn the treating physician about a refractory course of oral
lesions that may help with counselling patients.
PMID- 28498562
TI - Effect of valve design and anticoagulation strategy on 30-day clinical outcomes
in transcatheter aortic valve replacement: Results from the BRAVO 3 randomized
trial.
AB - BACKGROUND: Selection of valve type and procedural anticoagulant may impact
bleeding and vascular complications in transfemoral transcatheter aortic valve
replacement (TAVR). We sought to compare outcomes by valve [balloon expandable
(BE) or non-BE] and anticoagulant [bivalirudin vs. unfractionated heparin (UFH)]
type from the BRAVO-3 trial. METHODS: BRAVO-3 was a randomized multicenter trial
including 500 BE-TAVR and 282 non-BE TAVR patients, randomized to bivalirudin
versus UFH. Selection of valve type was at the discretion of the operator but
randomization was stratified according to valve type. Total follow up was to 30
days. We examined the incidence of Bleeding Academic Research Consortium type
>=3b bleeding, major vascular complications and all ischemic outcomes at 30-days.
Outcomes were adjusted using logistic regression analysis. RESULTS: Of the trial
cohort, 63.9% were treated with BE valves (n = 251 bivalirudin vs. n = 249 UFH)
and 36.1% with non-BE valves (n = 140 bivalirudin vs. n = 142 UFH). Patients
treated with non-BE valves were older, with higher euroSCORE I. At 30 days, there
were nonsignificant differences between the two valve types for adjusted risk of
all-cause death (HR 2.07, 95% CI 0.91-4.70, P = 0.084) and major vascular
complications (HR 1.78, 95% CI 0.97-3.26, P = 0.062) with non-BE compared with BE
valves, but all other outcomes were similar. A significant interaction was
observed between valve and anticoagulant type, with lower risk of major vascular
complications with bivalirudin compared with UFH in non-BE TAVR (P-interaction =
0.039). CONCLUSIONS: Majority of patients in the BRAVO 3 trial received BE
valves. At 30-days, adjusted risk of clinical outcomes was similar with non-BE
vs. BE valves. A significant interaction was observed between valve type and
procedural anticoagulant for lower risk of major vascular complications with
bivalirudin versus UFH in non-BE TAVR.
PMID- 28498564
TI - Spatial Bayesian latent factor regression modeling of coordinate-based meta
analysis data.
AB - Now over 20 years old, functional MRI (fMRI) has a large and growing literature
that is best synthesised with meta-analytic tools. As most authors do not share
image data, only the peak activation coordinates (foci) reported in the article
are available for Coordinate-Based Meta-Analysis (CBMA). Neuroimaging meta
analysis is used to (i) identify areas of consistent activation; and (ii) build a
predictive model of task type or cognitive process for new studies (reverse
inference). To simultaneously address these aims, we propose a Bayesian point
process hierarchical model for CBMA. We model the foci from each study as a
doubly stochastic Poisson process, where the study-specific log intensity
function is characterized as a linear combination of a high-dimensional basis
set. A sparse representation of the intensities is guaranteed through latent
factor modeling of the basis coefficients. Within our framework, it is also
possible to account for the effect of study-level covariates (meta-regression),
significantly expanding the capabilities of the current neuroimaging meta
analysis methods available. We apply our methodology to synthetic data and
neuroimaging meta-analysis datasets.
PMID- 28498565
TI - C-reactive protein gene polymorphism predicts the risk of thromboembolic stroke
in patients with atrial fibrillation: a more than 10-year prospective follow-up
study.
AB - : Essentials We studied the C-reactive protein (CRP) gene on stroke risk in
atrial fibrillation (AF) patients. 725 patients with CRP triallelic polymorphism
genotype were followed-up for more than 10 years. Patients with the A-390/T-390
allele of the CRP gene were more likely to get ischemic stroke. The triallelic
polymorphism of the CRP is related to ischemic stroke in AF patients. SUMMARY:
Background Little evidence is available regarding the impact of genetic
polymorphisms on the risk of thromboembolic stroke in patients with atrial
fibrillation (AF). An increasing body of evidence is demonstrating that
inflammatory responses play an important role in the pathophysiology of AF.
Objectives To investigate the effect of genetic polymorphisms of the C-reactive
protein (CRP) gene on the incidence of thromboembolic stroke in patients with AF.
Methods A total of 725 AF patients were longitudinally followed up for > 10
years; this is the largest and longest AF follow-up cohort with genetic data. CRP
promoter triallelic polymorphisms (C-390A and C-390T) were genotyped, and CRP
levels were divided into four quartiles. Results Patients with higher CRP levels
were more likely to develop thromboembolic stroke than those with lower CRP
levels (P<0.001, log-rank test for comparison of four quartiles). After
adjustment for conventional risk factors, patients with higher CRP levels were
more likely to develop thromboembolic stroke than those in the lowest CRP
quartile (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.08-4.81; the
lowest CRP quartile was the reference group). Patients carrying the A-390 or T
390 allele had higher CRP levels (3.35 +/- 2.71 mg L-1 versus 2.43 +/- 2.00 mg L
1 ), and were more likely to develop thromboembolic stroke, even after adjustment
for conventional risk factors (HR 2.07, 95% CI 1.23-3.48). Conclusion The CRP
triallelic polymorphism and the CRP level are associated with the risk of
incident thromboembolic stroke in patients with AF.
PMID- 28498566
TI - Synergistic effects of fibronectin and bone morphogenetic protein on the
bioactivity of titanium metal.
AB - To improve the biological properties of bioactive titanium metal, recombinant
human bone morphogenetic protein 2(rhBMP-2) and fibronectin (Fn) were adsorbed on
its surface solely or contiguously to modify the anodic oxidized titanium (AO
Ti), acid-alkali-treated titanium (AA-Ti), and polished titanium (P-Ti). It is
found that the different bioactive titanium surface structures had great
influence on protein adsorption. The adsorption amounts of BMP adsorbed solely
and Fn/BMP adsorbed contiguously were AA-Ti > P-Ti > AO-Ti, and that for Fn
adsorbed solely was AA-Ti ~ P-Ti > AO-Ti. The conformation of proteins was
changed remarkably after the adsorption. For BMP, the alpha-helix decreased on AA
Ti and stabilized on P-Ti and AO-Ti. For Fn, the beta-sheet on PT-Ti and AA-Ti
increased significantly. For Fn/BMP, the percentage of beta-sheet on AA-Ti
increased, and that of alpha-helix on all samples was stable. MSCs showed greater
adhesion and spreading on Fn/BMP groups. MTT and Elisa tests showed that the
synergistic effects of proteins made the cells proliferate and differentiate
faster. It indicated both the surface structure and the synergistic effects of
proteins could influence the biological properties of titanium metals. It
provides research foundation for improving the biological properties of bioactive
titanium metals by simultaneous application of several proteins. (c) 2017 Wiley
Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2485-2498, 2017.
PMID- 28498567
TI - Uterine fibroids: from observational epidemiology to clinical management.
PMID- 28498569
TI - Report on WPA activities in the triennium 2014-2017.
PMID- 28498568
TI - Reconstitution of immune cell populations in multiple sclerosis patients after
autologous stem cell transplantation.
AB - Multiple sclerosis is an inflammatory T cell-mediated autoimmune disease. In a
Phase II clinical trial, high-dose immunosuppressive therapy combined with
autologous CD34+ haematopoietic stem cell transplant resulted in 69.2% of
subjects remaining disease-free without evidence of relapse, loss of neurological
function or new magnetic resonance imaging (MRI) lesions to year 5 post
treatment. A combination of CyTOF mass cytometry and multi-parameter flow
cytometry was used to explore the reconstitution kinetics of immune cell subsets
in the periphery post-haematopoietic cell transplant (HSCT) and the impact of
treatment on the phenotype of circulating T cells in this study population.
Repopulation of immune cell subsets progressed similarly for all patients studied
2 years post-therapy, regardless of clinical outcome. At month 2, monocytes and
natural killer (NK) cells were proportionally more abundant, while CD4 T cells
and B cells were reduced, relative to baseline. In contrast to the changes
observed at earlier time-points in the T cell compartment, B cells were
proportionally more abundant and expansion in the proportion of naive B cells was
observed 1 and 2 years post-therapy. Within the T cell compartment, the
proportion of effector memory and late effector subsets of CD4 and CD8 T cells
was increased, together with transient increases in proportions of CD45RA
regulatory T cells (Tregs ) and T helper type 1 (Th1 cells) and a decrease in
Th17.1 cells. While none of the treatment effects studied correlated with
clinical outcome, patients who remained healthy throughout the 5-year study had
significantly higher absolute numbers of memory CD4 and CD8 T cells in the
periphery prior to stem cell transplantation.
PMID- 28498570
TI - Migration and psychosis: our smoking lung?
PMID- 28498571
TI - Shared decision making in mental health care settings: Perspective, purpose and
practice.
PMID- 28498572
TI - Drug use disorders: impact of a public health rather than a criminal justice
approach.
PMID- 28498573
TI - A reassessment of the relationship between depression and all-cause mortality in
3,604,005 participants from 293 studies.
PMID- 28498574
TI - Integrated care for mental, neurological and substance use disorders in non
specialized health settings: rising to the challenge.
PMID- 28498575
TI - Implementing shared decision making in routine mental health care.
AB - Shared decision making (SDM) in mental health care involves clinicians and
patients working together to make decisions. The key elements of SDM have been
identified, decision support tools have been developed, and SDM has been
recommended in mental health at policy level. Yet implementation remains limited.
Two justifications are typically advanced in support of SDM. The clinical
justification is that SDM leads to improved outcome, yet the available empirical
evidence base is inconclusive. The ethical justification is that SDM is a right,
but clinicians need to balance the biomedical ethical principles of autonomy and
justice with beneficence and non-maleficence. It is argued that SDM is
"polyvalent", a sociological concept which describes an idea commanding
superficial but not deep agreement between disparate stakeholders. Implementing
SDM in routine mental health services is as much a cultural as a technical
problem. Three challenges are identified: creating widespread access to high
quality decision support tools; integrating SDM with other recovery-supporting
interventions; and responding to cultural changes as patients develop the normal
expectations of citizenship. Two approaches which may inform responses in the
mental health system to these cultural changes - social marketing and the
hospitality industry - are identified.
PMID- 28498576
TI - A critique of the "ultra-high risk" and "transition" paradigm.
AB - The transdiagnostic expression of psychotic experiences in common mental disorder
(anxiety/depression/substance use disorder) is associated with a poorer
prognosis, and a small minority of people may indeed develop a clinical picture
that meets criteria for schizophrenia. However, it appears neither useful nor
valid to observe early states of multidimensional psychopathology in young people
through the "schizo"-prism, and apply misleadingly simple, unnecessary and
inefficient binary concepts of "risk" and "transition". A review of the "ultra
high risk" (UHR) or "clinical high risk" (CHR) literature indicates that UHR/CHR
samples are highly heterogeneous and represent individuals diagnosed with common
mental disorder (anxiety/depression/substance use disorder) and a degree of
psychotic experiences. Epidemiological research has shown that psychotic
experiences are a (possibly non-causal) marker of the severity of
multidimensional psychopathology, driving poor outcome, yet notions of "risk" and
"transition" in UHR/CHR research are restrictively defined on the basis of
positive psychotic phenomena alone, ignoring how baseline differences in
multidimensional psychopathology may differentially impact course and outcome.
The concepts of "risk" and "transition" in UHR/CHR research are measured on the
same dimensional scale, yet are used to produce artificial diagnostic shifts. In
fact, "transition" in UHR/CHR research occurs mainly as a function of variable
sample enrichment strategies rather than the UHR/CHR "criteria" themselves.
Furthermore, transition rates in UHR/CHR research are inflated as they do not
exclude false positives associated with the natural fluctuation of dimensional
expression of psychosis. Biological associations with "transition" thus likely
represent false positive findings, as was the initial claim of strong effects of
omega-3 polyunsatured fatty acids in UHR samples. A large body of UHR/CHR
intervention research has focused on the questionable outcome of "transition",
which shows lack of correlation with functional outcome. It may be more
productive to consider the full range of person-specific psychopathology in all
young individuals who seek help for mental health problems, instead of "policing"
youngsters for the transdiagnostic dimension of psychosis. Instead of the
relatively inefficient medical high-risk approach, a public health perspective,
focusing on improved access to a low-stigma, high-hope, small scale and youth
specific environment with acceptable language and interventions may represent a
more useful and efficient strategy.
PMID- 28498577
TI - News from WPA Scientific Sections.
PMID- 28498578
TI - Why ultra high risk criteria for psychosis prediction do not work well outside
clinical samples and what to do about it.
PMID- 28498579
TI - Common sense alone is not enough.
PMID- 28498580
TI - The role of expectations in mental disorders and their treatment.
PMID- 28498582
TI - Mating, sexual selection, and the evolution of schizophrenia.
PMID- 28498581
TI - The contemporary refugee crisis: an overview of mental health challenges.
AB - There has been an unprecedented upsurge in the number of refugees worldwide, the
majority being located in low-income countries with limited resources in mental
health care. This paper considers contemporary issues in the refugee mental
health field, including developments in research, conceptual models, social and
psychological interventions, and policy. Prevalence data yielded by cross
sectional epidemiological studies do not allow a clear distinction to be made
between situational forms of distress and frank mental disorder, a shortcoming
that may be addressed by longitudinal studies. An evolving ecological model of
research focuses on the dynamic inter-relationship of past traumatic experiences,
ongoing daily stressors and the background disruptions of core psychosocial
systems, the scope extending beyond the individual to the conjugal couple and the
family. Although brief, structured psychotherapies administered by lay
counsellors have been shown to be effective in the short term for a range of
traumatic stress responses, questions remain whether these interventions can be
sustained in low-resource settings and whether they meet the needs of complex
cases. In the ideal circumstance, a comprehensive array of programs should be
provided, including social and psychotherapeutic interventions, generic mental
health services, rehabilitation, and special programs for vulnerable groups.
Sustainability of services, ensuring best practice, evidence-based approaches,
and promoting equity of access must remain the goals of future developments, a
daunting challenge given that most refugees reside in settings where skills and
resources in mental health care are in shortest supply.
PMID- 28498583
TI - Neuroticism is a fundamental domain of personality with enormous public health
implications.
PMID- 28498585
TI - Correction.
PMID- 28498584
TI - Risk of suicide, deliberate self-harm and psychiatric illness after the loss of a
close relative: A nationwide cohort study.
AB - The loss of a close relative is a common event, yet it is associated with
increased risk of serious mental health conditions. No large-scale study has
explored up to now the importance of the bereaved person's relation to the
deceased while accounting for gender and age. We performed a nationwide Danish
cohort study using register information from 1995 through 2013 on four sub
cohorts including all persons aged >=18 years exposed to the loss of a child,
spouse, sibling or parent. We identified 1,445,378 bereaved persons, and each was
matched by gender, age and family composition to five non-bereaved persons.
Cumulative incidence proportions were calculated to estimate absolute differences
in suicide, deliberate self-harm and psychiatric illness. Cox proportional hazard
regression was used to calculate hazard ratios while adjusting for potential
confounders. Results revealed that the risk of suicide, deliberate self-harm and
psychiatric illness was increased in the bereaved cohorts for at least 10 years
after the loss, particularly during the first year. During that year, the risk
difference was 18.9 events in 1,000 persons after loss of a child (95% CI: 17.6
20.1) and 16.0 events in 1,000 persons after loss of the spouse (95% CI: 15.4
16.6). Hazard ratios were generally highest after loss of a child, in younger
persons, and after sudden loss by suicide, homicide or accident. One in three
persons with a previous psychiatric diagnosis experienced suicide, deliberate
self-harm or psychiatric illness within the first year of bereavement. In
conclusion, this study shows that the risk of suicide, deliberate self-harm and
psychiatric illness is high after the loss of a close relative, especially in
susceptible subgroups. This suggests the need for early identification of high
risk persons displaying adjustment problems after loss of a close family member,
in order to reduce the risk of serious mental health outcomes.
PMID- 28498586
TI - Psychiatric practice: caring for patients, collaborating with partners, or
marketing to consumers?
PMID- 28498587
TI - Does neuroimaging have a role in predicting outcomes in psychosis?
PMID- 28498588
TI - The clinical relevance of appraisals of psychotic experiences.
PMID- 28498589
TI - Mental health shared decision making in the US.
PMID- 28498590
TI - Validity and utility of the general factor of psychopathology.
PMID- 28498591
TI - Has the rising placebo response impacted antidepressant clinical trial outcome?
Data from the US Food and Drug Administration 1987-2013.
AB - More than fifteen years ago, it was noted that the failure rate of antidepressant
clinical trials was high, and such negative outcomes were thought to be related
to the increasing magnitude of placebo response. However, there is considerable
debate regarding this phenomenon and its relationship to outcomes in more recent
antidepressant clinical trials. To investigate this, we accessed the US Food and
Drug Administration (FDA) reviews for sixteen antidepressants (85 trials, 115
trial arms, 23,109 patients) approved between 1987 and 2013. We calculated the
magnitude of placebo and antidepressant responses, antidepressant-placebo
differences, as well as the effect sizes and success rates, and compared these
measures over time. Exploratory analysis investigated potential changes in trial
design and conduct over time. As expected, the magnitude of placebo response has
steadily grown in the past 30 years, increasing since 2000 by 6.4% (r=0.46,
p<0.001). Contrary to expectations, a similar increase has occurred in the
magnitude of antidepressant response (6.0%, r=0.37, p<0.001). Thus, the effect
sizes (0.30 vs. 0.29, p=0.42) and the magnitude of antidepressant-placebo
differences (10.5% vs. 10.3%, p=0.37) have remained statistically equivalent.
Furthermore, the frequency of positive trial arms has gone up in the past 15
years (from 47.8% to 63.8%), but this difference in frequency has not reached
statistical significance. Trial design features that were previously associated
with a possible lower magnitude of placebo response were not implemented, and
their relationship to the magnitude of placebo response could not be replicated.
Of the 34 recent trials, two implemented enhanced interview techniques, but both
of them were unsuccessful. The results of this study suggest that the
relationship between the magnitude of placebo response and the outcome of
antidepressant clinical trials is weak at best. These data further indicate that
antidepressant-placebo differences are about the same for all of the sixteen
antidepressants approved by the FDA in the past thirty years.
PMID- 28498592
TI - WPA International Competency-Based Curriculum for Mental Health Providers on
Intimate Partner Violence and Sexual Violence Against Women.
PMID- 28498593
TI - Involvement in decision making: the devil is in the detail.
PMID- 28498594
TI - Persistent persecutory delusions: The spirit, style and content of targeted
treatment.
PMID- 28498596
TI - Shared decision making: everyone wants it, so why isn't it happening?
PMID- 28498595
TI - Etiology in psychiatry: embracing the reality of poly-gene-environmental
causation of mental illness.
AB - Intriguing findings on genetic and environmental causation suggest a need to
reframe the etiology of mental disorders. Molecular genetics shows that thousands
of common and rare genetic variants contribute to mental illness. Epidemiological
studies have identified dozens of environmental exposures that are associated
with psychopathology. The effect of environment is likely conditional on genetic
factors, resulting in gene-environment interactions. The impact of environmental
factors also depends on previous exposures, resulting in environment-environment
interactions. Most known genetic and environmental factors are shared across
multiple mental disorders. Schizophrenia, bipolar disorder and major depressive
disorder, in particular, are closely causally linked. Synthesis of findings from
twin studies, molecular genetics and epidemiological research suggests that joint
consideration of multiple genetic and environmental factors has much greater
explanatory power than separate studies of genetic or environmental causation.
Multi-factorial gene-environment interactions are likely to be a generic
mechanism involved in the majority of cases of mental illness, which is only
partially tapped by existing gene-environment studies. Future research may cut
across psychiatric disorders and address poly-causation by considering multiple
genetic and environmental measures across the life course with a specific focus
on the first two decades of life. Integrative analyses of poly-causation
including gene-environment and environment-environment interactions can realize
the potential for discovering causal types and mechanisms that are likely to
generate new preventive and therapeutic tools.
PMID- 28498597
TI - Incorporating shared decision making in mental health care requires translating
knowledge from implementation science.
PMID- 28498598
TI - Prevention and early intervention for borderline personality disorder: a novel
public health priority.
PMID- 28498600
TI - Causes and predictors of premature death in first-episode schizophrenia spectrum
disorders.
PMID- 28498601
TI - Shared decision making: a consideration of historical and political contexts.
PMID- 28498602
TI - Treatment of people at ultra-high risk for psychosis.
PMID- 28498599
TI - Prevalence, incidence and mortality from cardiovascular disease in patients with
pooled and specific severe mental illness: a large-scale meta-analysis of
3,211,768 patients and 113,383,368 controls.
AB - : People with severe mental illness (SMI) - schizophrenia, bipolar disorder and
major depressive disorder - appear at risk for cardiovascular disease (CVD), but
a comprehensive meta-analysis is lacking. We conducted a large-scale meta
analysis assessing the prevalence and incidence of CVD; coronary heart disease;
stroke, transient ischemic attack or cerebrovascular disease; congestive heart
failure; peripheral vascular disease; and CVD-related death in SMI patients
(N=3,211,768) versus controls (N=113,383,368) (92 studies). The pooled CVD
prevalence in SMI patients (mean age 50 years) was 9.9% (95% CI: 7.4-13.3).
Adjusting for a median of seven confounders, patients had significantly higher
odds of CVD versus controls in cross-sectional studies (odds ratio, OR=1.53, 95%
CI: 1.27-1.83; 11 studies), and higher odds of coronary heart disease (OR=1.51,
95% CI: 1.47-1.55) and cerebrovascular disease (OR=1.42, 95% CI: 1.21-1.66).
People with major depressive disorder were at increased risk for coronary heart
disease, while those with schizophrenia were at increased risk for coronary heart
disease, cerebrovascular disease and congestive heart failure. Cumulative CVD
incidence in SMI patients was 3.6% (95% CI: 2.7-5.3) during a median follow-up of
8.4 years (range 1.8-30.0). Adjusting for a median of six confounders, SMI
patients had significantly higher CVD incidence than controls in longitudinal
studies (hazard ratio, HR=1.78, 95% CI: 1.60-1.98; 31 studies). The incidence was
also higher for coronary heart disease (HR=1.54, 95% CI: 1.30-1.82),
cerebrovascular disease (HR=1.64, 95% CI: 1.26-2.14), congestive heart failure
(HR=2.10, 95% CI: 1.64-2.70), and CVD-related death (HR=1.85, 95% CI: 1.53-2.24).
People with major depressive disorder, bipolar disorder and schizophrenia were
all at increased risk of CVD-related death versus controls. CVD incidence
increased with antipsychotic use (p=0.008), higher body mass index (p=0.008) and
higher baseline CVD prevalence (p=0.03) in patients vs. CONTROLS: Moreover, CVD
prevalence (p=0.007), but not CVD incidence (p=0.21), increased in more recently
conducted studies. This large-scale meta-analysis confirms that SMI patients have
significantly increased risk of CVD and CVD-related mortality, and that elevated
body mass index, antipsychotic use, and CVD screening and management require
urgent clinical attention.
PMID- 28498603
TI - Calciphylaxis in haemodialysed patients: diagnostic value of calcifications in
cutaneous biopsy.
PMID- 28498604
TI - Postoperative interventions to reduce inflammatory complications after third
molar surgery: review of the current evidence.
AB - Inflammatory complications such as pain, swelling, trismus, infection and
alveolar osteitis have an adverse affect on the quality of life of patients after
third molar removal. This review presents the current evidence on postoperative
strategies to reduce these complications. A literature search was performed to
identify articles published in English between 2000 to 2016 using the following
keywords: third molar(s), wisdom tooth/teeth, pain, swelling, trismus, infection,
alveolar osteitis and dry socket. In total, 221 papers were reviewed. Methods
published included analgesics, antibiotics, corticosteroids, mouthwashes, topical
gels, cryotherapy and ozone therapy. This review highlights the variability in
evidence available and summarizes the findings from best-quality evidence. In
conclusion, paracetamol and ibuprofen are efficacious in managing postoperative
pain. Corticosteroids and antibiotics should only be used in selected cases.
Chlorhexidine reduces alveolar osteitis. The benefits of cryotherapy,
postoperative irrigation and ozone gel are yet to be established.
PMID- 28498605
TI - Brain structural connectivity and context-dependent extinction memory.
AB - BACKGROUND: Extinction of conditioned fear represents an important mechanism in
the treatment of anxiety disorders. Return of fear after successful extinction or
exposure therapy in patients with anxiety disorders might be linked to poor
temporal or contextual generalization of extinction due to individual differences
in brain structural connectivity. The goal of this magnetic resonance imaging
study was therefore to investigate the association of context-dependent
extinction recall with brain structural connectivity. METHODS: Diffusion-tensor
imaging was used to determine the fractional anisotropy as a measure of white
matter structural integrity of fiber tracts connecting central brain regions of
the fear and extinction circuit (uncinate fasciculus, cingulum). Forty-five
healthy men participated in a two-day fear conditioning experiment with fear
acquisition in context A and extinction learning in context B on the first day.
Extinction recall in the extinction context as well as renewal in the acquisition
context and a novel context C took place one day later. RESULTS: Renewal of
conditioned fear (skin conductance responses) in the acquisition context was
associated with higher structural integrity of the hippocampal part of the
cingulum. CONCLUSIONS: Enhanced structural integrity of the cingulum might be
related to stronger hippocampal modulation of the dorsal anterior cingulate
cortex, a region important for modulating conditioned fear output by excitatory
projections to the amygdala. This finding underpins the crucial role of
individual differences in the structural integrity of relevant fiber tracts for
context-dependent extinction recall and return of fear after exposure therapy in
anxiety disorders.
PMID- 28498606
TI - Is uvulopalatopharyngoplasty effective in obstructive sleep apnea?
PMID- 28498608
TI - Computed tomography scanning in mycosis fungoides: optimizing the balance between
benefit and harm.
PMID- 28498607
TI - Human hepatocellular carcinomas with a periportal phenotype have the lowest
potential for early recurrence after curative resection.
AB - : Hepatocellular carcinomas (HCCs) exhibit a diversity of molecular phenotypes,
raising major challenges in clinical management. HCCs detected by surveillance
programs at an early stage are candidates for potentially curative therapies
(local ablation, resection, or transplantation). In the long term,
transplantation provides the lowest recurrence rates. Treatment allocation is
based on tumor number, size, vascular invasion, performance status, functional
liver reserve, and the prediction of early (<2 years) recurrence, which reflects
the intrinsic aggressiveness of the tumor. Well-differentiated, potentially low
aggressiveness tumors form the heterogeneous molecular class of nonproliferative
HCCs, characterized by an approximate 50% beta-catenin mutation rate. To define
the clinical, pathological, and molecular features and the outcome of
nonproliferative HCCs, we constructed a 1,133-HCC transcriptomic metadata set and
validated findings in a publically available 210-HCC RNA sequencing set. We show
that nonproliferative HCCs preserve the zonation program that distributes
metabolic functions along the portocentral axis in normal liver. More precisely,
we identified two well-differentiated, nonproliferation subclasses, namely
periportal-type (wild-type beta-catenin) and perivenous-type (mutant beta
catenin), which expressed negatively correlated gene networks. The new periportal
type subclass represented 29% of all HCCs; expressed a hepatocyte nuclear factor
4A-driven gene network, which was down-regulated in mouse hepatocyte nuclear
factor 4A knockout mice; were early-stage tumors by Barcelona Clinic Liver
Cancer, Cancer of the Liver Italian Program, and tumor-node-metastasis staging
systems; had no macrovascular invasion; and showed the lowest metastasis-specific
gene expression levels and TP53 mutation rates. Also, we identified an eight-gene
periportal-type HCC signature, which was independently associated with the
highest 2-year recurrence-free survival by multivariate analyses in two
independent cohorts of 247 and 210 patients. CONCLUSION: Well-differentiated HCCs
display mutually exclusive periportal or perivenous zonation programs. Among all
HCCs, periportal-type tumors have the lowest intrinsic potential for early
recurrence after curative resection. (Hepatology 2017;66:1502-1518).
PMID- 28498609
TI - Cytologic diagnosis of mammary neoplastic and non-neoplastic diseases in dogs.
PMID- 28498610
TI - Diabetes distress is linked with worsening diabetes management over time in
adults with Type 1 diabetes.
AB - AIM: To determine the cross-sectional and longitudinal associations between
diabetes distress and diabetes management. METHODS: In a non-interventional
study, 224 adults with Type 1 diabetes were assessed for diabetes distress,
missed insulin boluses, hypoglycaemic episodes, and HbA1c at baseline and 9
months. RESULTS: At baseline, greater distress was associated with higher HbA1c
and a greater percentage of missed insulin boluses. Longitudinally, elevated
baseline distress was related to increased missed insulin boluses, and decreases
in distress were associated with decreases in HbA1c . In supplementary analyses,
neither depression symptoms nor a diagnosis of major depressive disorder was
associated with missed insulin boluses, HbA1c or hypoglycaemic episodes in cross
sectional or longitudinal analyses. CONCLUSIONS: Significant cross-sectional and
longitudinal associations were found between diabetes distress and management; in
contrast, no parallel associations were found for major depressive disorder or
depression symptoms. Findings suggest that elevated distress may lead to more
missed insulin boluses over time, suggesting a potential intervention target. The
covarying association between distress and HbA1c points to the complex and likely
interactive associations between these constructs. Findings highlight the need to
address distress as an integral part of diabetes management in routine care.
PMID- 28498611
TI - Design, Synthesis, and Biological Evaluation of Peptidomimetic N-Substituted Cbz
4-Hyp-Hpa-Amides as Novel Inhibitors of Plasmodium falciparum.
AB - A new series of peptidomimetic N-substituted Cbz-4-Hyp-Hpa-amides were designed,
synthesized, and evaluated for inhibition of the Plasmodium falciparum.
Substituents on the N-atom of the amide group were selected alkyl-, allyl-, aryl
, 2-hydroxyethyl-, 2-cyanoethyl-, cyanomethyl-, 2-hydroxyethyl-, 2,2
diethoxyethyl-, or 2-ethoxy-2-oxoethylamino groups, and about of 40 new compounds
were synthesized and evaluated for antiplasmodial activity in vitro. Antimalarial
activity has been investigated as for the final peptide mimetics, and their
immediate predecessors, carrying TBDMS or TBDPS protecting groups on 4
hydroxyproline residue and 18 derivatives exhibited toxicity against P.
falciparum. Of these agents, compound 23e was shown to have potent antimalarial
activity with IC50 528 ng/ml.
PMID- 28498612
TI - Design of a modulated orthovoltage stereotactic radiosurgery system.
AB - PURPOSE: To achieve stereotactic radiosurgery (SRS) dose distributions with sharp
gradients using orthovoltage energy fluence modulation with inverse planning
optimization techniques. METHODS: A pencil beam model was used to calculate dose
distributions from an orthovoltage unit at 250 kVp. Kernels for the model were
derived using Monte Carlo methods. A Genetic Algorithm search heuristic was used
to optimize the spatial distribution of added tungsten filtration to achieve dose
distributions with sharp dose gradients. Optimizations were performed for depths
of 2.5, 5.0, and 7.5 cm, with cone sizes of 5, 6, 8, and 10 mm. In addition to
the beam profiles, 4pi isocentric irradiation geometries were modeled to examine
dose at 0.07 mm depth, a representative skin depth, for the low energy beams.
Profiles from 4pi irradiations of a constant target volume, assuming maximally
conformal coverage, were compared. Finally, dose deposition in bone compared to
tissue in this energy range was examined. RESULTS: Based on the results of the
optimization, circularly symmetric tungsten filters were designed to modulate the
orthovoltage beam across the apertures of SRS cone collimators. For each depth
and cone size combination examined, the beam flatness and 80-20% and 90-10%
penumbrae were calculated for both standard, open cone-collimated beams as well
as for optimized, filtered beams. For all configurations tested, the modulated
beam profiles had decreased penumbra widths and flatness statistics at depth.
Profiles for the optimized, filtered orthovoltage beams also offered decreases in
these metrics compared to measured linear accelerator cone-based SRS profiles.
The dose at 0.07 mm depth in the 4pi isocentric irradiation geometries was higher
for the modulated beams compared to unmodulated beams; however, the modulated
dose at 0.07 mm depth remained <0.025% of the central, maximum dose. The 4pi
profiles irradiating a constant target volume showed improved statistics for the
modulated, filtered distribution compared to the standard, open cone-collimated
distribution. Simulations of tissue and bone confirmed previously published
results that a higher energy beam (>= 200 keV) would be preferable, but the 250
kVp beam was chosen for this work because it is available for future
measurements. CONCLUSIONS: A methodology has been described that may be used to
optimize the spatial distribution of added filtration material in an orthovoltage
SRS beam to result in dose distributions with decreased flatness and penumbra
statistics compared to standard open cones. This work provides the mathematical
foundation for a novel, orthovoltage energy fluence-modulated SRS system.
PMID- 28498613
TI - A Series of Bimetallic Ammonium AlNa Formates.
AB - A series of AlNa bimetallic ammonium metal formate frameworks (AlNa AMFFs) have
been prepared by employing various ammoniums from NH4+ to large linear
polyammoniums. The series consists of six perovskites of (412 ?63 ) topology for
mono-ammoniums, two chiral (49 ?66 ) frameworks incorporating polyethylene
ammoniums, two niccolites with (412 ?63 )(49 ?66 ) topology containing
diammoniums, and two layered compounds made of 2D (4,4) AlNa formate sheets
intercalated by small diammoniums. The first ten compounds present the structural
hierarchy of (412 ?63 )m (49 ?66 )n framework topologies for (m, n)=(1, 0), (0,
1), and (1, 1), respectively, in parallel to the homometallic AMFFs for divalent
metals. The symmetry lowering, asymmetric formate bridges, and different hydrogen
bonding strengths appeared in the bimetallic structures owing to the different
charge and size of Al3+ and Na+ seemingly inhibits the occurrence of phase
transitions for more than half the AlNa AMFFs within the series, and the
bimetallic members undergoing phase transitions show different transition
behaviors and dielectric properties compared with the homometallic analogs.
Anisotropic/negative/zero thermal expansions of the materials could be rationally
attributed to the librational motion, or flip movement between different sites,
of the ammonium cations, and the coupled change of AlNa formate frameworks. The
thermal and IR spectroscopic properties have also been investigated.
PMID- 28498615
TI - Understanding the impact of haemodialysis on UK National Health Service patients'
well-being: A qualitative investigation.
AB - AIMS AND OBJECTIVES: While haemodialysis is an effective treatment for end-stage
renal disease, the requirements and restrictions it imposes on patients can be
onerous. The aim of this study was to obtain UK National Health Service patients'
perspectives on the challenges arising from haemodialysis with the intention of
identifying potential improvements. BACKGROUND: Depression rates are particularly
high in those with end-stage renal disease; however, there is limited insight
into the range of stressors associated with haemodialysis treatment within the
National Health Service contributing to such high rates, particularly those of a
cognitive or psychological nature. DESIGN: A qualitative approach was used to
obtain rich, patient-focused data; one-to-one semi-structured interviews were
conducted with twenty end-stage renal disease at a UK National Health Service
centre. METHODS: Patients were interviewed during a typical haemodialysis
session. Thematic analysis was used to systematically interpret the data. Codes
were created in an inductive and cyclical process using a constant comparative
approach. RESULTS: Three themes emerged from the data: (i) fluctuations in
cognitive/physical well-being across the haemodialysis cycle, (ii) restrictions
arising from the haemodialysis treatment schedule, (iii) emotional impact of
haemodialysis on the self and others. The findings are limited to predominantly
white, older patients (median = 74 years) within a National Health Service
setting. CONCLUSIONS: Several of the experiences reported by patients as
challenging and distressing have so far been overlooked in the literature. A
holistic-based approach to treatment, acknowledging all aspects of a patient's
well-being, is essential if optimal quality of life is to be achieved by
healthcare providers. RELEVANCE TO CLINICAL PRACTICE: The findings can be used to
inform future interventions and guidelines aimed at improving patients' treatment
adherence and outcomes, for example, improved reliable access to mental health
specialists.
PMID- 28498616
TI - Tethering Formation to Resorption: Reversal Revisited.
PMID- 28498614
TI - Hepatic uptake of conjugated bile acids is mediated by both sodium taurocholate
cotransporting polypeptide and organic anion transporting polypeptides and
modulated by intestinal sensing of plasma bile acid levels in mice.
AB - : The Na+ -taurocholate cotransporting polypeptide (NTCP/SLC10A1) is believed to
be pivotal for hepatic uptake of conjugated bile acids. However, plasma bile acid
levels are normal in a subset of NTCP knockout mice and in mice treated with
myrcludex B, a specific NTCP inhibitor. Here, we elucidated which transport
proteins mediate the hepatic uptake of conjugated bile acids and demonstrated
intestinal sensing of elevated bile acid levels in plasma in mice. Mice or
healthy volunteers were treated with myrcludex B. Hepatic bile acid uptake
kinetics were determined in wild-type (WT), organic anion transporting
polypeptide (OATP) knockout mice (lacking Slco1a/1b isoforms), and human OATP1B1
transgenic mice. Effects of fibroblast growth factor 19 (FGF19) on hepatic
transporter mRNA levels were assessed in rat hepatoma cells and in mice by
peptide injection or adeno-associated virus-mediated overexpression. NTCP
inhibition using myrcludex B had only moderate effects on bile acid kinetics in
WT mice, but completely inhibited active transport of conjugated bile acid
species in OATP knockout mice. Cholesterol 7alpha-hydroxylase Cyp7a1 expression
was strongly down-regulated upon prolonged inhibition of hepatic uptake of
conjugated bile acids. Fgf15 (mouse counterpart of FGF19) expression was induced
in hypercholanemic OATP and NTCP knockout mice, as well as in myrcludex B-treated
cholestatic mice, whereas plasma FGF19 was not induced in humans treated with
myrcludex B. Fgf15/FGF19 expression was induced in polarized human enterocyte
models and mouse organoids by basolateral incubation with a high concentration (1
mM) of conjugated bile acids. CONCLUSION: NTCP and OATPs contribute to hepatic
uptake of conjugated bile acids in mice, whereas the predominant uptake in humans
is NTCP mediated. Enterocytes sense highly elevated levels of (conjugated) bile
acids in the systemic circulation to induce FGF15/19, which modulates hepatic
bile acid synthesis and uptake. (Hepatology 2017;66:1631-1643).
PMID- 28498617
TI - Segmental resection is a safe oncological alternative to total proctocolectomy in
elderly patients with ulcerative colitis and malignancy.
AB - AIM: The standard approach for the surgical management of colorectal cancer (CRC)
in the setting of ulcerative colitis (UC) involves total proctocolectomy (TPC).
However, some patients also undergo a partial resection (PR). This may be an
attractive option in older patients with a high risk for surgery. The aim of this
study was to compare the risk of metachronous cancer after PR or TPC for CRC in
the setting of UC. METHOD: This was a retrospective cohort study conducted
through the Nationwide Veterans Affairs Healthcare System (VA). Patients who had
UC and underwent a PR or TPC for CRC were followed from the time of their surgery
to their most recent clinical follow-up. The primary outcome was development of
metachronous cancer in the PR group. Secondary outcomes included surgical and
medical outcomes. RESULTS: Fifty-nine patients were included: 24 (40.7%)
underwent PR and 35 (59.3%) underwent TPC. The median age at cancer diagnosis was
73.0 and 61.7 years in PR and TPC groups, respectively (P < 0.0005). Amongst
patients undergoing PR, 15 (60%) had no active UC at the time of surgery, whereas
in patients undergoing TPC, at the time of surgery eight (23.5%) had no active UC
(P = 0.005). No patient who underwent a partial colectomy developed a
metachronous cancer in the retained colonic segment during the follow-up period
(median 7 years). CONCLUSION: Our study suggests that PR for CRC in the setting
of UC may be a viable option in a selected cohort of patients, especially among
the elderly.
PMID- 28498619
TI - Race.
PMID- 28498618
TI - Phase I clinical trial of cell division associated 1 (CDCA1) peptide vaccination
for castration resistant prostate cancer.
AB - Cell division associated 1 (CDCA1) was screened as an oncogene that is
overexpressed on several cancers, including prostate cancer. A highly immunogenic
HLA-A*2402-restricted epitope peptide corresponding to part of the CDCA1 protein
was also identified. A phase I clinical trial was conducted for patients with
castration resistant prostate cancer (CRPC) using a CDCA1 peptide vaccination.
Twelve patients having HLA-A*2402 with CRPC after failure of docetaxel
chemotherapy were enrolled. They received subcutaneous administration of the
CDCA1 peptide as an emulsion with Montanide ISA51VG once a week in a dose
escalation manner (doses of 1.0 or 3.0 mg/body, six patients received each dose).
The primary endpoint was safety, and the secondary endpoints were the
immunological and clinical responses. Vaccination with CDCA1 peptide was well
tolerated without any serious adverse events. Peptide-specific cytotoxic T
lymphocyte (CTL) responses using ELISPOT assay and dextramer assay were observed
in three patients receiving the 1.0 mg dose and five patients receiving the 3.0
mg dose. The median overall survival time was 11.0 months and specific CTL
reacting to CDCA1 peptide were recognized in long-surviving patients. CDCA1
derived peptide vaccine treatment was tolerable and might effectively induce
peptide-specific CTLs for CRPC patients. This novel peptide vaccine therapy for
CRPC appears promising. (ClinicalTrials.gov number, NCT01225471).
PMID- 28498620
TI - Ultrahigh Thermal Conductive yet Superflexible Graphene Films.
AB - Electrical devices generate heat at work. The heat should be transferred away
immediately by a thermal manager to keep proper functions, especially for high
frequency apparatuses. Besides high thermal conductivity (K), the thermal manager
material requires good foldability for the next generation flexible electronics.
Unfortunately, metals have satisfactory ductility but inferior K (<=429 W m-1 K-1
), and highly thermal-conductive nonmetallic materials are generally brittle.
Therefore, fabricating a foldable macroscopic material with a prominent K is
still under challenge. This study solves the problem by folding atomic thin
graphene into microfolds. The debris-free giant graphene sheets endow graphene
film (GF) with a high K of 1940 +/- 113 W m-1 K-1 . Simultaneously, the
microfolds render GF superflexible with a high fracture elongation up to 16%,
enabling it more than 6000 cycles of ultimate folding. The large-area
multifunctional GFs can be easily integrated into high-power flexible devices for
highly efficient thermal management.
PMID- 28498621
TI - Enhanced production of enveloped viruses in BST-2-deficient cell lines.
AB - Despite all the advantages that cell-cultured influenza vaccines have over egg
based influenza vaccines, the inferior productivity of cell-culture systems is a
major drawback that must be addressed. BST-2 (tetherin) is a host restriction
factor which inhibits budding-out of various enveloped viruses from infected host
cells. We developed BST-2-deficient MDCK and Vero cell lines to increase
influenza virus release in cell culture. BST-2 gene knock-out resulted in
increased release of viral particles into the culture medium, by at least 2-fold
and up to 50-fold compared to release from wild-type counterpart cells depending
on cell line and virus type. The effect was not influenza virus/MDCK/Vero
specific, but was also present in a broad range of host cells and virus families;
we observed similar results in murine, human, canine, and monkey cell lines with
viruses including MHV-68 (Herpesviridae), influenza A virus (Orthomyxoviridae),
porcine epidemic diarrhea virus (Coronaviridae), and vaccinia virus (Poxviridae).
Our results suggest that the elimination of BST-2 expression in virus-producing
cell lines can enhance the production of viral vaccines. Biotechnol.
Bioeng.2017;114: 2289-2297. (c) 2017 Wiley Periodicals, Inc.
PMID- 28498622
TI - Regulation of RAW264.7 macrophage polarization on smooth and rough surface
topographies by galectin-3.
AB - Recognition of topographical features induces phenotypic changes in macrophages
although the receptors and signaling pathways are not completely characterized.
As integrin molecules in focal adhesions/podosomes are in intimate contact with
topography and topography modulates the NFkB pathway through cholesterol enriched
raft-associated adhesive signaling structures we hypothesized that a cell-surface
signaling complex comprised of galectin-3 together with its ligand CD98 and
integrinbeta1 is important for topography-directed lineage determination. This
study used polished, sand blasted and acid etched (SLA) surfaces and two novel
grooved topographies (G1 and G2) produced by anisotropic etching of Si <1 1 0> to
evaluate the role of galectin-3 in macrophage polarization in RAW 264.7
macrophages, as determined by gene expression and morphology. In the presence of
the galectin-3 inhibitor, lactose, the M2 marker (mannose receptor) was down
regulated while the M1 marker (iNOS) was up-regulated on smooth and rough
surfaces. This skewing of phenotype suggests a role for galectin-3 in macrophage
polarization towards the M2 phenotype. Additionally, we evaluated the role of
PI3K on polarization using PI3K inhibitor LY294002. We found that the M2 marker
was down-regulated on both PO (surface polished) and G1 surfaces implicating PI3K
in lineage determination. We also found that surface topography altered cell
morphology; macrophages had a larger area on G2 surfaces. Lactose treatment
significantly reduced the cell area on all topographies suggesting that the
galectin-3 is also involved in signaling complexes triggering the rearrangement
of the actin cytoskeleton. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res
Part A: 105A: 2499-2509, 2017.
PMID- 28498623
TI - Interplay of Electronic Cooperativity and Exchange Coupling in Regulating the
Reactivity of Diiron(IV)-oxo Complexes towards C-H and O-H Bond Activation.
AB - Activation of inert C-H bonds such as those of methane are extremely challenging
for chemists but in nature, the soluble methane monooxygenase (sMMO) enzyme
readily oxidizes methane to methanol by using a diiron(IV) species. This has
prompted chemists to look for similar model systems. Recently, a (MU-oxo)bis(MU
carboxamido)diiron(IV) ([FeIV2 O(L)2 ]2+ L=N,N-bis-(3',5'-dimethyl-4'
methoxypyridyl-2'-methyl)-N'-acetyl-1,2-diaminoethane) complex has been generated
by bulk electrolysis and this species activates inert C-H bonds almost 1000 times
faster than mononuclear FeIV =O species and at the same time selectively
activates O-H bonds of alcohols. The very high reactivity and selectivity of this
species is puzzling and herein we use extensive DFT calculations to shed light on
this aspect. We have studied the electronic and spectral features of diiron
{FeIII -MU(O)-FeIII }+2 (complex I), {FeIII -MU(O)-FeIV }+3 (II), and {FeIV
MU(O)-FeIV }+4 (III) complexes. Strong antiferromagnetic coupling between the Fe
centers leads to spin-coupled S=0, S=3/2, and S=0 ground state for species I-III
respectively. The mechanistic study of the C-H and O-H bond activation reveals a
multistate reactivity scenario where C-H bond activation is found to occur
through the S=4 spin-coupled state corresponding to the high-spin state of
individual FeIV centers. The O-H bond activation on the other hand, occurs
through the S=2 spin-coupled state corresponding to an intermediate state of
individual FeIV centers. Molecular orbital analysis reveals sigma-pi/pi-pi
channels for the reactivity. The nature of the magnetic exchange interaction is
found to be switched during the course of the reaction and this offers lower
energy pathways. Significant electronic cooperativity between two metal centers
during the course of the reaction has been witnessed and this uncovers the reason
behind the efficiency and selectivity observed. The catalyst is found to
prudently choose the desired spin states based on the nature of the substrate to
effect the catalytic transformations. These findings suggest that the presence of
such factors play a role in the reactivity of dinuclear metalloenzymes such as
sMMO.
PMID- 28498624
TI - Additional benefit of using a risk-based selection for prostate biopsy: an
analysis of biopsy complications in the Rotterdam section of the European
Randomized Study of Screening for Prostate Cancer.
AB - OBJECTIVE: To investigate biopsy complications and hospital admissions that could
be reduced by the use of European Randomized Study of Screening for Prostate
Cancer (ERSPC) risk calculators. MATERIALS AND METHODS: All biopsies performed in
the Rotterdam section of the ERSPC between 1993 and 2015 were included. Biopsy
complications and hospital admission data were prospectively recorded in
questionnaires that were completed 2 weeks after biopsy. The ERSPC risk
calculators 3 (RC3) and 4 (RC4) were applied to men attending the first and
subsequent rounds of screening, respectively. Applying the predefined RC3/4
probability thresholds for prostate cancer (PCa) risk of >=12.5% and high-grade
PCa risk >=3%, we assessed the number of complications, admissions and costs that
could be reduced by avoiding biopsies in men below these thresholds. RESULTS: A
total of 10 747 biopsies with complete questionnaires were included. For these
biopsies a complication rate of 67.9% (7294/10 747), a post-biopsy fever rate of
3.9% (424/10747) and a hospital admission rate of 0.9% (92/10747) were recorded.
The fever rate was found to be static over the years, but the hospital admission
rate tripled from 0.6% (1993-1996) to 2.1% (2009-2015). Among 7704 biopsies which
fit the criteria for RC3 or RC4, 35.8% of biopsies (2757/7704), 37.4% of
complications (1972/5268), 39.4% of fever events (128/325) and 42.3% of
admissions (30/71) could have been avoided by using one of the risk calculators.
More complications could have been avoided if RC4 had been used and for more
recent biopsies (2009-2015). Our findings show that 35.9% of the total cost of
biopsies and complication treatment could have been avoided. CONCLUSION: A
significant proportion of biopsy complications, hospital admissions and costs
could be reduced if biopsy decisions were based on ERSPC risk calculators instead
of PSA only. This effect was most prominent in more recent biopsies and in men
with repeated biopsies or screening.
PMID- 28498625
TI - Biomechanics of the human uterus.
AB - The appropriate biomechanical function of the uterus is required for the
execution of human reproduction. These functions range from aiding the transport
of the embryo to the implantation site, to remodeling its tissue walls to host
the placenta, to protecting the fetus during gestation, to contracting forcefully
for a safe parturition and postpartum, to remodeling back to its nonpregnant
condition to renew the cycle of menstruation. To serve these remarkably diverse
functions, the uterus is optimally geared with evolving and contractile muscle
and tissue layers that are cued by chemical, hormonal, electrical, and mechanical
signals. The relationship between these highly active biological signaling
mechanisms and uterine biomechanical function is not completely understood for
normal reproductive processes and pathological conditions such as adenomyosis,
endometriosis, infertility and preterm labor. Animal studies have illuminated the
rich structural function of the uterus, particularly in pregnancy. In humans,
medical imaging techniques in ultrasound and magnetic resonance have been
combined with computational engineering techniques to characterize the uterus in
vivo, and advanced experimental techniques have explored uterine function using
ex vivo tissue samples. The collective evidence presented in this review gives an
overall perspective on uterine biomechanics related to both its nonpregnant and
pregnant function, highlighting open research topics in the field. Additionally,
uterine disease and infertility are discussed in the context of tissue injury and
repair processes and the role of computational modeling in uncovering etiologies
of disease. WIREs Syst Biol Med 2017, 9:e1388. doi: 10.1002/wsbm.1388 For further
resources related to this article, please visit the WIREs website.
PMID- 28498626
TI - Risk of labor dystocia increases with maternal age irrespective of parity: a
population-based register study.
AB - INTRODUCTION: Advanced maternal age is associated with labor dystocia (LD) in
nulliparous women. This study investigates the age-related risk of LD in first,
second and third births. MATERIAL AND METHODS: All live singleton cephalic births
at term (>= 37 gestational weeks) recorded in the Swedish Medical Birth Register
from 1999 to 2011, except elective cesarean sections and fourth births and more,
in total 998 675 pregnancies, were included in the study. LD was defined by
International Classification of Diseases, version 10 codes (O620, O621, O622,
O629, O630, O631 and O639). In each parity group risks of LD at age 25-29 years,
30-34 years, 35-39 years and >= 40 years compared with age < 25 years were
investigated by logistic regression analyses. Analyses were adjusted for year of
delivery, education, country/region of birth, smoking in early pregnancy,
maternal height, body mass index, week of gestation, fetal presentation and
infant birthweight. RESULTS: Rates of LD were 22.5%, 6.1% and 4% in first, second
and third births, respectively. Adjusted odd ratios (OR) for LD increased
progressively from the youngest to the oldest age group, irrespective of parity.
At age 35-39 years the adjusted OR (95% CI) was approximately doubled compared
with age 25 and younger: 2.13 (2.06-2.20) in first birth; 2.05 (1.91-2.19) in
second births; and 1.81 (1.49-2.21) in third births. CONCLUSIONS: Maternal age is
an independent risk factor for LD in first, second and third births. Although age
related risks by parity are relatively similar, more nulliparous than parous
women will be exposed to LD due to the higher rate.
PMID- 28498628
TI - Erratum: High speed sCMOS-based oblique plane microscopy applied to the study of
calcium dynamics in cardiac myocytes: [J. Biophotonics 9, No. 3, 311-323 (2016)].
AB - In the article by M.B. Sikkel et al. (doi: 10.1002/jbio.201500193), published in
J. Biophotonics 9, 311-323 (2016), an error occurred in the computer code that
was used to generate Figure 3. This erratum is published to correct Figure 3, the
calculated value of tgeom and the experimentally determined value of toptics in
the text of the article.
PMID- 28498627
TI - A UK community-based survey on the prevalence of rhinosinusitis.
AB - OBJECTIVES: There is limited information about the prevalence of rhinosinusitis
in the UK community. This study aimed to identify its prevalence and investigate
any association with demographic variables. The secondary aims were to determine
the degree of impairment, impact on quality of life and any costs incurred by
patients. DESIGN: We used a modified version (MSNOT-20) of a quality-of-life
instrument, the sinonasal outcome test-20 (SNOT-20), in a small and successful
pilot project. It was then used in a community-based survey and a second phase 6
months later to test repeatability. Nasal examination and comparison of its
quality-of-life section with other health-related quality-of-life tools occurred
in the second phase. SETTING AND PARTICIPANTS: The questionnaire was administered
by post to 2000 Farnborough (UK) residents, selected through stratified
randomisation. The relation of an abnormal MSNOT-20 score with hay fever, asthma,
smoking, food allergy, work productivity and social limitation was also analysed.
MAIN OUTCOME AND RESULTS: The response rate was 79.8%; over thirty per cent of
the community suffer from upper respiratory tract symptoms with impact on
multiple domains of quality of life including emotional, financial costs and loss
of days at work. The MSNOT-20 provided a more sensitive assessment of health
related quality of life than the Short Form 36 questionnaire. CONCLUSION:
Rhinosinusitis is prevalent in the Farnborough community and associated with
significant morbidity and impairment on quality of life. The MSNOT-20 is a useful
disease-specific quality-of-life tool in rhinosinusitis.
PMID- 28498629
TI - Biophotonics.World - More than just a news page: The largest biophotonics network
worldwide.
PMID- 28498630
TI - The "appropriateness" of AUC for peripheral arterial disease: The story
continues....
PMID- 28498631
TI - Marijuana Use in Pregnancy: Concerns in an Evolving Era.
AB - Marijuana is the most commonly used illicit drug in pregnancy, and the prevalence
of use during pregnancy is increasing in the United States. Although much of the
existing research investigating marijuana use in pregnancy is limited by study
design and confounding factors, a growing accumulation of data suggests adverse
outcomes. Studies have identified associations with decreased birth weight,
increased spontaneous preterm birth, and impaired neurodevelopment among children
and adults with in utero exposure. Moderate concentrations of marijuana have also
been identified in breast milk. Due to these findings, multiple professional
societies have issued clear statements against marijuana use during pregnancy and
lactation.
PMID- 28498632
TI - Robotic microlaryngeal phonosurgery: Testing of a "steady-hand" microsurgery
platform.
AB - OBJECTIVES/HYPOTHESIS: To evaluate gains in microlaryngeal precision achieved by
using a novel robotic "steady hand" microsurgery platform in performing simulated
phonosurgical tasks. STUDY DESIGN: Crossover comparative study of surgical
performance and descriptive analysis of surgeon feedback. METHODS: A novel
robotic ear, nose, and throat microsurgery system (REMS) was tested in simulated
phonosurgery. Participants navigated a 0.4-mm-wide microlaryngeal needle through
spirals of varying widths, both with and without robotic assistance. Fail time
(time the needle contacted spiral edges) was measured, and statistical comparison
was performed. Participants were surveyed to provide subjective feedback on the
REMS. RESULTS: Nine participants performed the task at three spiral widths,
yielding 27 paired testing conditions. In 24 of 27 conditions, robot-assisted
performance was better than unassisted; five trials were errorless, all achieved
with the robot. Paired analysis of all conditions revealed fail time of 0.769 +/-
0.568 seconds manually, improving to 0.284 +/- 0.584 seconds with the robot (P =
.003). Analysis of individual spiral sizes showed statistically better
performance with the REMS at spiral widths of 2 mm (0.156 +/- 0.226 seconds vs.
0.549 +/- 0.545 seconds, P = .019) and 1.5 mm (0.075 +/- 0.099 seconds vs. 0.890
+/- 0.518 seconds, P = .002). At 1.2 mm, all nine participants together showed
similar performance with and without robotic assistance (0.621 +/- 0.923 seconds
vs. 0.868 +/- 0.634 seconds, P = .52), though subgroup analysis of five surgeons
most familiar with microlaryngoscopy showed statistically better performance with
the robot (0.204 +/- 0.164 seconds vs. 0.664 +/- 0.354 seconds, P = .036).
CONCLUSIONS: The REMS is a novel platform with potential applications in
microlaryngeal phonosurgery. Further feasibility studies and preclinical testing
should be pursued as a bridge to eventual clinical use. LEVEL OF EVIDENCE: NA.
Laryngoscope, 128:126-132, 2018.
PMID- 28498633
TI - How does radioactive iodine affect the nose?
AB - OBJECTIVES/HYPOTHESIS: To determine the effect of radioactive iodine (RAI)
treatment on the nasal mucosa and nasal functions. STUDY DESIGN: Prospective
clinical study. METHODS: This study included 41 patients (31 female and 10 male)
who were treated with RAI for papillary thyroid carcinoma. A visual analogue
scale (VAS) was used for subjective evaluation of nasal symptoms. The saccharine
test, nasal Schirmer test, and acoustic rhinometry were used for objective
evaluation of nasal functions. All tests were administered at baseline (before
RAI treatment), and then 1 month and 1 year post-RAI treatment. Only 21 of the
patients could be evaluated after 1 year of treatment and were included in the
study's analysis. RESULTS: VAS obstruction and dryness scores 1 month and 1 year
post-RAI were significantly higher than the baseline scores (P < .05 and P < .05,
respectively). Mean cross-sectional area values 1 month and 1 year post-RAI did
not differ significantly from baseline values (P > .05 and P > .05,
respectively). Schirmer test results 1 month and 1 year post-RAI treatment were
significantly lower than at baseline (P < .05 and P < .05, respectively).
Saccharine test results 1 month and 1 year post-RAI were significantly higher
than at baseline (P < .05). CONCLUSIONS: RAI treatment can adversely affect the
nasal mucosa. Nasal dryness and obstruction can occur immediately after RAI
treatment. Additional research is warranted to further elucidate the effects of
RAI treatment on nasal function. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:2698
2702, 2017.
PMID- 28498634
TI - Older people with Type 2 diabetes, including those with chronic kidney disease or
dementia, are commonly overtreated with sulfonylurea or insulin therapies.
AB - AIM: To evaluate potential overtreatment with sulfonylurea and insulin therapies
amongst older people with Type 2 diabetes, including those with chronic kidney
disease or dementia. METHODS: Using the ECLIPSE Live software tool, we developed
a search to examine data on older people (age >= 70 years) with Type 2 diabetes,
who were prescribed sulfonylurea or insulin therapies over the previous 90 days.
Sixteen Norfolk general practices participated, representing a population of 24
661 older people, including 3862 (15.7%) with Type 2 diabetes. Of these, 1379
(35.7%) people were prescribed sulfonylurea or insulin therapies. Data extracted
included age, sex, last recorded HbA1c value, renal function and dementia codes.
RESULTS: The median age of the study cohort was 78 years. A total of 644 people
(47.8%) had chronic kidney disease (estimated GFR < 60 mL/min/1.73m2 ) and 60
people (4.35%) had dementia. The median (interquartile range) HbA1c concentration
for the entire cohort was 58 (51-69) mmol/mol [7.5 (6.8-8.5)%], with no
difference in median HbA1c between those with or without either chronic kidney
disease or dementia. In total, 400 older people (29.9%) had an HbA1c
concentration < 53 mmol/mol (7%), of whom 162 (12.1%) had HbA1c < 48 mmol/mol
(6.5%). Stratified by prescription for sulfonylurea, insulin or combined insulin
and sulfonylurea therapies, 282 (35.2%), 93 (24.2%) and 25 people (16.3%),
respectively, had HbA1c < 53 mmol/mol (7.0%). Treatment to an HbA1c target of <
53 mmol/mol (7.0%) was as prevalent in those with chronic kidney disease or
dementia as in those without. CONCLUSION: In the present cohort of older people
with Type 2 diabetes prescribed sulfonylurea or insulin therapies, overtreatment
was common, even in the presence of comorbidities known to increase hypoglycaemia
risk.
PMID- 28498635
TI - SNX10 Plays a Critical Role in MMP9 Secretion via JNK-p38-ERK Signaling Pathway.
AB - Matrix metalloproteinases (MMPs) plays a critical role in the degradation of
extracellular matrix (ECM). Sorting nexin (SNX) 10 is a member of the SNX family,
which functions in regulation of endosomal sorting and osteoclast activation, has
been implicated to play an important role in the bone erosion of rheumatoid
arthritis. In this study, we aimed to investigate the possible role of SNX10 on
MMP9 secretion and the potential mechanism. By immunostaining and co
immunoprecipitation, we found that SNX10 was extensively co-localized with MMP9,
indicating that SNX10 might participate in MMP9 trafficking. After knocking down
SNX10 via siRNA, the secretion and activity of MMP9 was significantly reduced,
but the amount of protein was increased. By contraries, over-expression of SNX10
could increase the secretion and activity levels. Deficiency of SNX10 impaired
the differentiation and bone resorption function of osteoclast, with a low
activity of MMP9 compared to WT one. In SNX10 knockout osteoclast, the
phosphorylation levels of JNK, p38, and ERK were obviously down-regulated. Our
results first identified the role of SNX10 in MMP9 trafficking and secretion, and
provided an evidence for SNX10 as a possible therapeutic target for bone
destructing disease. J. Cell. Biochem. 118: 4664-4671, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28498636
TI - Study protocol evaluating the use of bowel stimulation before loop ileostomy
closure to reduce postoperative ileus: a multicenter randomized controlled trial.
AB - AIM: Postoperative ileus is the most commonly observed morbidity following
ileostomy closure. Studies have demonstrated that the defunctionalized bowel of a
loop ileostomy undergoes a series of functional and structural changes, such as
atrophy of the intestinal villi and muscular layers, which may contribute to
ileus. A single-centre study in Spain demonstrated that preoperative bowel
stimulation via the distal limb of the loop ileostomy decreased postoperative
ileus, length of stay and time to gastrointestinal function. METHOD: A
multicentre randomized controlled trial involving patients from Canadian
institutions was designed to evaluate the effect of preoperative bowel
stimulation before ileostomy closure on postoperative ileus. Stimulation will
include canalizing the distal limb of the ileostomy loop with an 18Fr Foley
catheter and infusing it with a solution of 500 ml of normal saline mixed with 30
g of a thickening agent (Nestle(c) Thicken-Up(c) ). This will be performed 10
times over the 3 weeks before ileostomy closure in an outpatient clinic setting
by a trained Enterostomal Therapy nurse. Surgeons and the treating surgical team
will be blinded to their patient's group allocation. Data regarding patient
demographics, and operative and postoperative variables, will be collected
prospectively. Primary outcome will be postoperative ileus, defined as an
intolerance to oral food in the absence of clinical or radiological signs of
obstruction, that either requires nasogastric tube insertion or is associated
with two of the following on or after post-operative day 3: nausea/vomiting;
abdominal distension; and the absence of flatus. Secondary outcomes will include
length of stay, time to tolerating a regular diet, time to first passage of
flatus or stool and overall morbidity. A cost analysis will be performed to
compare the costs of conventional care with conventional care plus preoperative
stimulation. DISCUSSION: This manuscript discusses the potential benefits of
preoperative bowel stimulation in improving postoperative outcomes and outlines
our protocol for the first multicenter study to evaluate preoperative bowel
stimulation before ileostomy closure. The results of this study could have
considerable implications for the care of patients undergoing ileostomy closure.
PMID- 28498637
TI - beta2-AR activation induces chemoresistance by modulating p53 acetylation through
upregulating Sirt1 in cervical cancer cells.
AB - It has been suggested that beta2-adrenergic receptor (beta2-AR)-mediated
signaling induced by catecholamines regulates the degradation of p53. However,
the underlying molecular mechanisms were not known. In the present study, we
demonstrated that catecholamines upregulated the expression of silent information
regulator 1 (Sirt1) through activating beta2-AR-mediated signaling pathway, since
selective beta2-AR antagonist ICI 118, 551 and non-selective beta-blocker
proprenolol effectively repressed isoproterenol (ISO)-induced Sirt1 expression.
Catecholamines inhibited doxorubicin (DOX)-induced p53 acetylation and
transcription-activation activities by inducing the expression of Sirt1.
Knockdown of the Sirt1 expression by the specific siRNA remarkably blocked the
inhibitory effects of ISO on DOX-induced p53 acetylation. In addition, we
demonstrated that catecholamines induced resistance of cervical cancer cells to
chemotherapeutics both in vitro and in vivo and that beta2-AR was overexpressed
in cervical cancer tissues. Our data suggest that the p53-dependent,
chemotherapeutics-induced cytotoxicity in cervical cancer cells may be
compromised by catecholamines-induced upregulation of the Sirt1 expression
through activating the beta2-AR signaling.
PMID- 28498638
TI - Assessing the Influence of Mutation on GTPase Transition States by Using X-ray
Crystallography, 19 F NMR, and DFT Approaches.
AB - We report X-ray crystallographic and 19 F NMR studies of the G-protein RhoA
complexed with MgF3- , GDP, and RhoGAP, which has the mutation Arg85'Ala. When
combined with DFT calculations, these data permit the identification of changes
in transition state (TS) properties. The X-ray data show how Tyr34 maintains
solvent exclusion and the core H-bond network in the active site by relocating to
replace the missing Arg85' sidechain. The 19 F NMR data show deshielding effects
that indicate the main function of Arg85' is electronic polarization of the
transferring phosphoryl group, primarily mediated by H-bonding to O3G and thence
to PG . DFT calculations identify electron-density redistribution and pinpoint
why the TS for guanosine 5'-triphosphate (GTP) hydrolysis is higher in energy
when RhoA is complexed with RhoGAPArg85'Ala relative to wild-type (WT) RhoGAP.
This study demonstrates that 19 F NMR measurements, in combination with X-ray
crystallography and DFT calculations, can reliably dissect the response of small
GTPases to site-specific modifications.
PMID- 28498639
TI - Three-year risk of high-grade CIN for women aged 30 years or older who undergo
baseline Pap cytology and HPV co-screening.
AB - BACKGROUND: Papanicolaou (Pap) cytology and high-risk human papillomavirus (HPV)
DNA cotesting for women aged >=30 years are recommended for the prevention of
cervical cancer. The objective of the current study was to evaluate the efficacy
of this cotesting for predicting the risk of high-grade cervical intraepithelial
neoplasia 3 (CIN3) during a 3-year follow-up period. METHODS: A retrospective
database search identified women aged >=30 years who had baseline HPV and Pap
cytology cotesting results in 2007 or 2008 and for whom 3-year follow-up results
were available. The cumulative 3-year risks of developing CIN-3 were calculated.
RESULTS: The 3-year follow-up data after baseline Pap/HPV cotesting were
available for 1986 women (mean age, 53 years). Of the 1668 women who had a
baseline Pap-negative (Pap-)/HPV- cotesting result, 1561 (93.6%) had a follow-up
Pap cytology result that was negative for intraepithelial lesions or malignancy.
Of the 1530 women who had follow-up Pap/HPV cotesting, 1504 (98.3%) had a Pap
/HPV- result. The 3-year cumulative risk of developing CIN-3 was found to be
highest for women with a baseline Pap-positive (Pap+)/HPV+ cotesting result
(12.5%); the risk of CIN-3 was lower in those with a Pap-/HPV+ result (1.5%; P =
.0032) or a Pap-/HPV- result (0.06%; P<.0001). The 3-year cumulative risk of CIN
3 was found to be significantly greater for women with an HPV+ result (4.8%)
compared with those with an HPV- result (0.06%; P<.0001). CONCLUSIONS: Pap
cytology and HPV cotesting are valuable for stratifying CIN-3 risk. Pap cytology
and HPV co-screening at a 3-year screening interval appears to carry a low risk
of CIN-3 for women who have a baseline Pap-/HPV- cotesting result. Cancer
Cytopathol 2017;125:644-51. (c) 2017 American Cancer Society.
PMID- 28498640
TI - Recent Advances in Synthetic alpha-Glucosidase Inhibitors.
AB - Over the past few years, the number of people diagnosed with type 2 diabetes has
increased owing to an unhealthy diet, a limited amount of exercise, and obesity.
The search for novel and efficient antidiabetes agents has become an urgent task
for scientists. Among the antidiabetes drugs, alpha-glucosidase inhibitor drugs
have been proven to have many advantages over other drugs, and therefore, a large
number of new compounds as alpha-glucosidase inhibitors has recently been
reported. In this review, we summarize these newly found alpha-glucosidase
inhibitors and their structure-activity relationships in antidiabetic studies and
provide better structures for alpha-glucosidase inhibitors or even preclinical
candidates. Beyond that, some enlightening strategies for the synthesis of
relevant compounds are highlighted.
PMID- 28498641
TI - Quaternary ammonium salts substituted by 5-phenyl-1,3,4-oxadiazole-2-thiol as
novel antibacterial agents with low cytotoxicity.
AB - Twenty-one novel 5-phenyl-1,3,4-oxadiazole-2-thiol (POT) substituted N
hydroxyethyl quaternary ammonium salts (6a-g, 7a-g, 8a-g) were prepared and
characterized by FTIR, NMR, and elemental analysis. Compounds 6a, 6c, and 8a were
confirmed by X-ray single-crystal diffraction. They display the unsurpassed
antibacterial activity against Staphylococcus aureus, alpha-H-tococcus,
Escherichia coli, P. aeruginosa, Proteus vulgaris, Canidia Albicans, especially
6g, 7g, 8g with dodecyl group. Compounds 8a-d with N,N-dihydroxyethyl and POT
groups display unsurpassed antibacterial activity and non-toxicity. The structure
activity relationships indicate that POT and flexible dihydroxyethyl group in QAS
are necessary for antibacterial activity and cytotoxicity. SEM and TEM images of
E. coli morphologies of 8d show the antibacterial agents can adhere to membrane
surfaces to inhibit bacterial growth by disrupting peptidoglycan formation and
releasing bacterial cytoplasm from cell membranes.
PMID- 28498642
TI - In Situ Probing of Ion Ordering at an Electrified Ionic Liquid/Au Interface.
AB - Charge transport at the interface of electrodes and ionic liquids is critical for
the use of the latter as electrolytes. A room-temperature ionic liquid, 1-ethyl
2,3-dimethylimidazolium bis(trifluoromethanesulfonyl)imide (EMMIM TFSI), is
investigated in situ under applied bias voltage with a novel method using low
energy electron and photoemission electron microscopy. Changes in photoelectron
yield as a function of bias applied to electrodes provide a direct measure of the
dynamics of ion reconfiguration and electrostatic responses of the EMMIM TFSI.
Long-range and correlated ionic reconfigurations that occur near the electrodes
are found to be a function of temperature and thickness, which, in turn, relate
to ionic mobility and different configurations for out-of-plane ordering near the
electrode interfaces, with a critical transition in ion mobility for films
thicker than three monolayers.
PMID- 28498643
TI - Esophageal dilation in head and neck cancer patients: A systematic review and
meta-analysis.
AB - OBJECTIVE: To characterize the safety profile and effectiveness of esophageal
dilation in head and neck cancer patients. METHODS: A systematic review was
undertaken for articles reporting outcomes of esophageal dilation in head and
neck cancer patients. The Medline, Scopus, Web of Science, and Cochrane databases
were searched in accordance with Preferred Reporting Items for Systematic Reviews
and Meta-Analyses guidelines. Complications related to esophageal dilation in
head and neck cancer patients was the primary outcome of interest. Success rates,
demographic data, cancer staging, and treatment data were assessed secondarily.
Statistical analyses included both qualitative and quantitative assessments. A
limited meta-analysis and pooling of the data was performed using a random
effects model. RESULTS: Of the collective 8,243 initial candidate articles, 15
retrospective studies containing data for a collective 449 patients were
ultimately included in the analysis. There was significant heterogeneity in the
outcomes data. With an overall complication rate of 10.6% (95% confidence
interval [CI]: 4.1%,17%) and a pooled success rate of 72.9% (95% CI: 65.7%,80.1%)
per patient, the articles generally supported the use of dilation. CONCLUSION:
Head and neck cancer patients experience a higher rate of complications following
dilation compared to patients with other causes of benign stricture. Esophageal
dilation is effective in improving dysphagia, but these benefits are often
transient and thus necessitate repeat interventions. Laryngoscope, 128:111-117,
2018.
PMID- 28498644
TI - Early versus late percutaneous revascularization in patients hospitalized with
non ST-segment elevation myocardial infarction: The atherosclerosis risk in
communities surveillance study.
AB - BACKGROUND: Current guidelines recommend early invasive intervention (<24 hr) for
high risk patients with non-ST-segment elevation myocardial infarction (NSTEMI).
A delayed invasive strategy (24-72 hr) is considered reasonable for low risk
patients. The real-world effectiveness of this strategy is unknown. METHODS: The
ARIC Study has conducted hospital surveillance of acute myocardial infarction
(MI) since 1987. NSTEMI was classified using a validated algorithm. We limited
our study to patients undergoing early (<24 hr of the event onset), or late (>=24
hr) percutaneous coronary intervention (PCI). Patients were stratified into low
(TIMI score 2-4), and high risk (TIMI score 5-7, or presence of cardiogenic
shock, ventricular fibrillation, or cardiac arrest). Associations between early
versus late PCI and mortality were analyzed using multivariable logistic
regression adjusted for demographics, hospitalization year, TIMI score, and
comorbidities. RESULTS: From 1987 to 2012, 6,746 patients were hospitalized with
NSTEMI and underwent PCI. Most were white (79%), male (68%), with mean age 61
years. The 28-day and 1-year mortality were 2% and 5%, respectively. Most
revascularizations (65%) were late. After accounting for potential confounders,
early PCI was associated with a 58% reduced 28-day mortality (OR = 0.42; 95% CI:
0.21-0.84) for the entire population, and 57% reduced mortality (OR = 0.43; 95%
CI: 0.21-0.88) for high risk patients. By 1-year of follow up, there was no
significant difference in mortality with respect to early vs. late PCI.
CONCLUSION: In hospitalized NSTEMI patients with high risk of clinical events,
early PCI is associated with improved 28-day survival.
PMID- 28498645
TI - Licochalcone A Suppresses Specificity Protein 1 as a Novel Target in Human Breast
Cancer Cells.
AB - Licochalcone A (LCA), isolated from the root of Glycyrrhiza inflata, are known to
have medicinal effect such as anti-oxidant, anti-bacterial, anti-viral, and anti
cancer. Though, as a pharmacological mechanism regulator, anti-cancer studies on
LCA were not investigated in human breast cancer. We investigated the anti
proliferative and apoptotic effect of LCA in human breast cancer cells MCF-7 and
MDA-MB-231 through MTS assay, PI staining, Annexin-V/7-AAD assay, mitochondrial
membrane potential assay, multi-caspase assay, RT-PCR, Western blot analysis, and
anchorage-independent cell transformation assay. Our results showed the little
difference between two cells, as MCF-7 cell is both estrogen/progesterone
receptor positive, there were only effect on Sp1 protein level, but not in mRNA
level. Adversely, estrogen/progesterone/human epidermal growth factor receptor 2
triple negative, MDA-MB-231 showed decreased Sp1 mRNA, and protein levels. To
confirm the participation of Sp1 in breast cancer cell viability, siRNA
techniques were introduced. Both cells showed dysfunction of mitochondrial
membrane potential and mitochondrial ROS production, which reflects it passed
intracellular mitochondrial apoptosis pathway. Additionally, LCA showed the anti
proliferative and apoptotic effect in breast cancer cells through regulating Sp1
and apoptosis-related proteins in a dose- and a time-dependent manner.
Consequently, LCA might be a potential anti-breast cancer drug substitute. J.
Cell. Biochem. 118: 4652-4663, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28498646
TI - Cook Cervical Ripening Balloon successfully prevents excessive hemorrhage
combined with ultrasound-guided suction curettage in the treatment of cesarean
scar pregnancy.
AB - AIM: Cesarean scar pregnancy (CSP) is a rare occurrence of ectopic pregnancy. CSP
incidence has increased significantly as a result of the increase in cesarean
section rates. At present, there are no standard treatment guidelines for CSP;
therefore, we report a minimally invasive treatment method for patients diagnosed
with CSP. METHODS: This study included 15 women who were diagnosed with CSP.
Ultrasound-guided suction curettage was performed on all patients. The Cook
Cervical Ripening Balloon was used to tamponade and prevent hemorrhage during the
procedure. In 12 patients, the balloon was placed immediately following
ultrasound-guided suction curettage; in two patients, the balloon was placed when
excessive bleeding occurred post-curettage; and in one patient, the balloon was
placed after the gestational sac evacuated by itself, and then suction aspiration
was performed on day 5, following the evacuation. Human chorionic gonadotropin
levels were evaluated three days after the procedure. RESULTS: Placement and
inflation of the Cook Cervical Ripening Balloon was well tolerated by all
patients. The balloon tamponade effectively reduced or prevented vaginal bleeding
in all patients, and none of the patients had an estimated blood loss higher than
1000 ml. CONCLUSIONS: Ultrasound-guided suction curettage is effective in the
treatment of CSP. The Cook Cervical Ripening Balloon is easy to place and inflate
and successfully prevented bleeding or assisted in the management of bleeding
complications. We recommend the Cook Cervical Ripening Balloon as an adjuvant
method for ultrasound-guided suction curettage for the treatment of CSP.
PMID- 28498647
TI - Association Between Staphylococcus aureus Bacteremia and Hospital Mortality in
Hemodialysis Patients With Bloodstream Infection: A Multicenter Cohort From
Japanese Tertiary Care Centers.
AB - Multiple studies have shown that Staphylococcus aureus bacteremia (SAB) has been
a major cause of death in hemodialysis patients. We examined whether SAB is a
risk for mortality among chronic hemodialysis patients in Japan where the
standard vascular access is arteriovenous fistula (AVF). This was a multicenter,
retrospective study of maintenance hemodialysis patients with bloodstream
infection (BSI) from 2011 to 2013 at tertiary care centers in Japan. The endpoint
was hospital mortality. Our cohort contained 32 SAB cases (14 MRSA and 18 MSSA)
and 42 non-SAB cases. Hospital mortality was higher among SAB cases than non-SAB
cases (46.9% vs. 23.8%, P = 0.038). In patients with BSI, SAB was significantly
associated with hospital mortality after adjustment for potential confounders,
including type of vascular access (OR 3.26). S. aureus was the leading cause of
BSI and hospital mortality among this cohort. Therefore, initial empiric
treatment should cover for S. aureus.
PMID- 28498648
TI - Extension of Pharmacy Copayments for Medications. Resolution of interim final
rule.
AB - The Department of Veterans Affairs (VA) notifies the public that an interim final
rule freezing medication copayments for veterans in priority groups 2 through 8,
published on December 7, 2016, was superseded by a final rule amending its
regulations concerning copayments that published on December 12, 2016. The
interim final rule received no public comments.
PMID- 28498649
TI - Payment or Reimbursement for Certain Medical Expenses for Camp Lejeune Family
Members. Final rule.
AB - The Department of Veterans Affairs (VA) adopts as final an interim final rule
addressing payment or reimbursement of certain medical expenses for family
members of Camp Lejeune veterans. Under this rule, VA reimburses family members,
or pays providers, for medical expenses incurred as a result of certain illnesses
and conditions that may be associated with contaminants present in the base water
supply at U.S. Marine Corps Base Camp Lejeune (Camp Lejeune), North Carolina,
from August 1, 1953, to December 31, 1987. Payment or reimbursement is made
within the limitations set forth in statute and Camp Lejeune family members
receive hospital care and medical services that are consistent with the manner in
which we provide hospital care and medical services to Camp Lejeune veterans. The
statutory authority has since been amended to also include certain veterans'
family members who resided at Camp Lejeune, North Carolina, for no less than 30
days (consecutive or nonconsecutive) between August 1, 1953, and December 31,
1987. This final rule will reflect that statutory change and will address public
comments received in response to the interim final rule.
PMID- 28498650
TI - Medicare Beneficiaries' High Out-of-Pocket Costs: Cost Burdens by Income and
Health Status.
AB - ISSUE: Fifty-six million people--17 percent of the U.S. population--rely on
Medicare. Yet, its benefits exclude dental, vision, hearing, and long-term
services, and it contains no ceiling on out-of-pocket costs for covered services,
exposing beneficiaries to high costs. GOAL: To inform discussion of possible
changes to Medicare, this issue brief looks at beneficiaries' out-of-pocket costs
by income and health status. METHODS: Spending estimates based on the Medicare
Current Beneficiary Survey.FINDINGS AND CONCLUSION: More than one-fourth of all
Medicare beneficiaries--15 million people--spend 20 percent or more of their
incomes on premiums plus medical care, including cost-sharing and uncovered
services. Beneficiaries with incomes below 200 percent of the poverty level (just
under $24,000 for a single person) and those with multiple chronic conditions or
functional limitations are at significant financial risk. Overall, beneficiaries
spent an average of $3,024 per year on out-of-pocket costs. Financial burdens and
access gaps highlight the need to approach reform with caution. Already-high
burdens suggest restructuring cost-sharing to ensure affordability and to provide
relief for low-income beneficiaries.
PMID- 28498652
TI - Mechanically-Controlled Reversible Spin Crossover of Single Fe-Porphyrin
Molecules.
AB - Spin-crossover (SCO) molecules are thought to be ideal systems for molecular
spintronics when SCO can be precisely controlled at the single-molecule level.
This is demonstrated here in the single-molecule junctions of Fe-porphyrin formed
in a scanning tunneling microscope. Experimentally, we find that the junctions
feature a zero-bias resonance in molecular conductance associated with the Fe
spin center. When mechanically stretching or squeezing the junctions by adjusting
the tip height, the line shape of the zero-bias resonance varies reversibly.
First-principles calculations reveal that widening the junction gap by 2 A
transforms the macrocyclic core hosting the Fe center from a saddle to a planar
conformation. This conformational change shortens the Fe-N bonds by 3%, which
changes the Fe spin state from S = 2 to S = 1.
PMID- 28498651
TI - Design of Benzoxathiazin-3-one 1,1-Dioxides as a New Class of Irreversible Serine
Hydrolase Inhibitors: Discovery of a Uniquely Selective PNPLA4 Inhibitor.
AB - The design and examination of 4,1,2-benzoxathiazin-3-one 1,1-dioxides as
candidate serine hydrolase inhibitors are disclosed, and represent the synthesis
and study of a previously unexplored heterocycle. This new class of activated
cyclic carbamates provided selective irreversible inhibition of a small subset of
serine hydrolases without release of a leaving group, does not covalently modify
active site catalytic cysteine and lysine residues of other enzyme classes, and
was found to be amenable to predictable structural modifications that modulate
intrinsic reactivity or active site recognition. Even more remarkable and within
the small pilot series of candidate inhibitors examined in an initial study, an
exquisitely selective inhibitor for a poorly characterized serine hydrolase
(PNPLA4, patatin-like phospholipase domain-containing protein 4) involved in
adipocyte triglyceride homeostasis was discovered.
PMID- 28498653
TI - Recovering Rare Earth Elements from Aqueous Solution with Porous Amine-Epoxy
Networks.
AB - Recovering aqueous rare earth elements (REEs) from domestic water sources is one
key strategy to diminish the U.S.'s foreign reliance of these precious
commodities. Herein, we synthesized an array of porous, amine-epoxy monolith and
particle REE recovery sorbents from different polyamine, namely
tetraethylenepentamine, and diepoxide (E2), triepoxide (E3), and tetra-epoxide
(E4) monomer combinations via a polymer-induced phase separation (PIPS) method.
The polyamines provided -NH2 (primary amine) plus -NH (secondary amine) REE
adsorption sites, which were partially reacted with C-O-C (epoxide) groups at
different amine/epoxide ratios to precipitate porous materials that exhibited a
wide range of apparent porosities and REE recoveries/affinities. Specifically,
polymer particles (ground monoliths) were tested for their recovery of La3+,
Nd3+, Eu3+, Dy3+, and Yb3+ (Ln3+) species from ppm-level, model REE solutions (pH
~ 2.4, 5.5, and 6.4) and a ppb-level, simulated acid mine drainage (AMD) solution
(pH ~ 2.6). Screening the sorbents revealed that E3/TEPA-88 (88% theoretical
reaction of -NH2 plus -NH) recovered, overall, the highest percentage of Ln3+
species of all particles from model 100 ppm- and 500 ppm-concentrated REE
solutions. Water swelling (monoliths) and ex situ, diffuse reflectance infrared
Fourier transform spectroscopy (DRIFTS) (ground monoliths/particles) data
revealed the high REE uptake by the optimized particles was facilitated by
effective distribution of amine and hydroxyl groups within a porous, phase
separated polymer network. In situ DRIFTS results clarified that phase
separation, in part, resulted from polymerization of the TEPA-E3 (N-N-diglycidyl
4-glycidyloxyaniline) species in the porogen via C-N bond formation, especially
at higher temperatures. Most importantly, the E3/TEPA-88 material cyclically
recovered >93% of ppb-level Ln3+ species from AMD solution in a recovery-strip
recovery scheme, highlighting the efficacy of these materials for practical
applications.
PMID- 28498654
TI - Template-Mediated Ni(II) Dispersion in Mesoporous SiO2 for Preparation of Highly
Dispersed Ni Catalysts: Influence of Template Type.
AB - Supported Ni catalysts on three mesoporous SiO2 supports (i.e., SBA-15, MCM-41,
and HMS) were prepared using a solid-state reaction between Ni(NO3)2 and organic
template-occluded mesoporous SiO2. For comparison, supported Ni catalysts on
mesoporous SiO2 synthesized by the conventional impregnation method were also
included. The catalysts were characterized by scanning electron microscopy, X-ray
diffraction, UV-vis diffuse reflectance spectroscopy, N2 adsorption, X-ray
photoelectron spectroscopy, H2 temperature-programmed reduction, transmission
electron microscopy, and transmission electron microscopy-energy-dispersive X
ray. The catalytic properties of the catalysts were evaluated using gas-phase
catalytic hydrodechlorination of 1,2-dichloroethane. The results showed that upon
grinding Ni(NO3)2 with template-occluded mesoporous SiO2, strong coordination
between Ni2+ and dodecylamine was identified in the Ni(NO3)2-HMS system.
Additionally, the results of H2 temperature-programmed reduction revealed that
NiO in calcined NiO/HMS was reduced at higher temperature than those in calcined
NiO/SBA-15 and NiO/MCM-41, reflecting the presence of a strong interaction
between NiO and mesoporous SiO2 in NiO/HMS. Consistently, the average particle
sizes of metallic Ni were found to be 2.7, 3.4, and 9.6 nm in H2-reduced Ni/HMS,
Ni/SBA-15, and Ni/MCM-41, respectively, indicative of a much higher Ni dispersion
in Ni/HMS. For the catalytic hydrodechlorination of 1,2-dichloroethane, Ni/MCM-41
synthesized by the solid-state reaction method exhibited a catalytic activity
similar to that prepared by the impregnation method, while higher catalytic
activities were observed on Ni/HMS and Ni/SBA-15 than on their counterparts
prepared by the impregnation method. Furthermore, a higher conversion was
identified on Ni/HMS than on Ni/SBA-15 and Ni/MCM-41, highlighting the importance
of template type for the preparation of highly dispersed metal catalysts on
mesoporous SiO2.
PMID- 28498655
TI - Discovery of an Orally Bioavailable Benzimidazole Diacylglycerol Acyltransferase
1 (DGAT1) Inhibitor That Suppresses Body Weight Gain in Diet-Induced Obese Dogs
and Postprandial Triglycerides in Humans.
AB - Modification of a gut restricted class of benzimidazole DGAT1 inhibitor 1 led to
9 with good oral bioavailability. The key structural changes to 1 include
bioisosteric replacement of the amide with oxadiazole and alpha,alpha
dimethylation of the carboxylic acid, improving DGAT1 potency and gut
permeability. Since DGAT1 is expressed in the small intestine, both 1 and 9 can
suppress postprandial triglycerides during acute oral lipid challenges in rats
and dogs. Interestingly, only 9 was found to be effective in suppressing body
weight gain relative to control in a diet-induced obese dog model, suggesting the
importance of systemic inhibition of DGAT1 for body weight control. 9 has
advanced to clinical investigation and successfully suppressed postprandial
triglycerides during an acute meal challenge in humans.
PMID- 28498656
TI - Occupational Exposure to Polycyclic Aromatic Hydrocarbon of Wildland Firefighters
at Prescribed and Wildland Fires.
AB - Wildland firefighters suppressing wildland fires or conducting prescribed fires
work long shifts during which they are exposed to high levels of wood smoke with
no respiratory protection. Polycyclic aromatic hydrocarbons (PAHs) are hazardous
air pollutants formed during incomplete combustion. Exposure to PAHs was measured
for 21 wildland firefighters suppressing two wildland fires and 4 wildland
firefighters conducting prescribed burns in California. Personal air samples were
actively collected using XAD4-coated quartz fiber filters and XAD2 sorbent tubes.
Samples were analyzed for 17 individual PAHs through extraction with
dichloromethane and gas chromatograph-mass spectrometer analysis. Naphthalene,
retene, and phenanthrene were consistently the highest measured PAHs. PAH
concentrations were higher at wildland fires compared to prescribed fires and
were highest for firefighters during job tasks that involve the most direct
contact with smoke near an actively burning wildland fire. Although
concentrations did not exceed current occupational exposure limits, wildland
firefighters are exposed to PAHs not only on the fire line at wildland fires, but
also while working prescribed burns and while off-duty. Characterization of
occupational exposures from wildland firefighting is important to understand
better any potential long-term health effects.
PMID- 28498657
TI - Surface-Enhanced Raman Spectroscopy: A Facile and Rapid Method for the Chemical
Component Study of Individual Atmospheric Aerosol.
AB - A simple and rapid method for detecting chemical components of individual aerosol
particles on Klarite substrate with surface-enhanced Raman spectroscopy (SERS) is
described. For both single simulated aerosol particles and ambient atmospheric
particles, this new analytical method promotes the enhancement factor of the
Raman signal. The spectra of ammonium sulfate and naphthalene particles at the
microscopic level are enhanced by a factor of 6 and therefore greatly improve the
detection of the chemical composition of an individual aerosol particle. When
aerosol particles are found over a microscopic domain, a set of Raman spectra
with chemical information can be obtained via SERS mapping. The maps illustrate
the distribution of organic or inorganic species on the SERS substrate. This
constitutes a facile and rapid method to study aerosol particles. This new method
allows the analysis of chemical composition in single aerosol particles,
demonstrating the power of SERS to probe the ambient atmospheric particles and to
study the formation of aerosol particles.
PMID- 28498659
TI - Modeling the Onset of Phase Separation in CaO-SiO2-CaCl2 Chlorine-Containing
Silicate Glasses.
AB - The addition of chlorine into a bioactive glass composition is expected to reduce
its abrasiveness and increase its bioactivity, which is important for dental
applications such as toothpastes. There is a lack of information and
understanding regarding the structural role of chlorine in chlorine-containing
bioactive silicate glasses. This has prompted classical core-shell model
molecular dynamics simulations of (50 - x/2)CaO-(50 - x/2)SiO2-xCaCl2 glasses to
be performed, where x ranges from x = 0.0 to 43.1 mol % CaCl2. These ternary
glasses are advantageous for a fundamental study because they do not have
additional network formers (e.g., phosphorus pentoxide) or modifiers (e.g.,
sodium) typically found in bioactive glass compositions. The (50 - x/2)CaO-(50 -
x/2)SiO2-xCaCl2 glasses were seen to become phase-separated around the x = 16.1
mol % CaCl2 composition, and chlorine predominantly coordinated with calcium.
These findings provide a solid foundation for further computational modeling work
on more complex chlorine-containing bioactive glass compositions.
PMID- 28498658
TI - Discovery of Clinical Candidate 1-{[(2S,3S,4S)-3-Ethyl-4-fluoro-5-oxopyrrolidin-2
yl]methoxy}-7-methoxyisoquinoline-6-carboxamide (PF-06650833), a Potent,
Selective Inhibitor of Interleukin-1 Receptor Associated Kinase 4 (IRAK4), by
Fragment-Based Drug Design.
AB - Through fragment-based drug design focused on engaging the active site of IRAK4
and leveraging three-dimensional topology in a ligand-efficient manner, a
micromolar hit identified from a screen of a Pfizer fragment library was
optimized to afford IRAK4 inhibitors with nanomolar potency in cellular assays.
The medicinal chemistry effort featured the judicious placement of lipophilicity,
informed by co-crystal structures with IRAK4 and optimization of ADME properties
to deliver clinical candidate PF-06650833 (compound 40). This compound displays a
5-unit increase in lipophilic efficiency from the fragment hit, excellent kinase
selectivity, and pharmacokinetic properties suitable for oral administration.
PMID- 28498660
TI - Self-Assembled Ruthenium(II)Porphyrin-Aluminium(III)Porphyrin-Fullerene Triad for
Long-Lived Photoinduced Charge Separation.
AB - A very efficient metal-mediated strategy led, in a single step, to a quantitative
construction of a new three-component multichromophoric system containing one
fullerene monoadduct, one aluminium(III) monopyridylporphyrin, and one
ruthenium(II) tetraphenylporphyrin. The Al(III) monopyridylporphyrin component
plays the pivotal role in directing the correct self-assembly process and behaves
as the antenna unit for the photoinduced processes of interest. A detailed study
of the photophysical behavior of the triad was carried out in different solvents
(CH2Cl2, THF, and toluene) by stationary and time-resolved emission and
absorption spectroscopy in the pico- and nanosecond time domains. Following
excitation of the Al-porphyrin, the strong fluorescence typical of this unit was
strongly quenched. The time-resolved absorption experiments provided evidence for
the occurrence of stepwise photoinduced electron and hole transfer processes,
leading to a charge-separated state with reduced fullerene acceptor and oxidized
ruthenium porphyrin donor. The time constant values measured in CH2Cl2 for the
formation of charge-separated state Ru-Al+-C60- (10 ps), the charge shift process
(Ru-Al+-C60- -> Ru+-Al-C60-), where a hole is transferred from Al-based to Ru
based unit (75 ps), and the charge recombination process to ground state (>5 ns),
can be rationalized within the Marcus theory. Although the charge-separating
performance of this triad is not outstanding, this study demonstrates that, using
the self-assembling strategy, improvements can be obtained by appropriate
chemical modifications of the individual molecular components.
PMID- 28498661
TI - Mesoporous Silica Nanoparticles-Encapsulated Agarose and Heparin as Anticoagulant
and Resisting Bacterial Adhesion Coating for Biomedical Silicone.
AB - Silicone catheter has been widely used in peritoneal dialysis. The research
missions of improving blood compatibility and the ability of resisting bacterial
adhesion of silicone catheter have been implemented for the biomedical
requirements. However, most of modification methods of surface modification were
only able to develop the blood-contacting biomaterials with good
hemocompatibility. It is difficult for the biomaterials to resist bacterial
adhesion. Here, agarose was selected to resist bacterial adhesion, and heparin
was chosen to improve hemocompatibility of materials. Both of them were loaded
into mesoporous silica nanoparticles (MSNs), which were successfully modified on
the silicone film surface via electrostatic interaction. Structures of the
mesoporous coatings were characterized in detail by dynamic light scattering,
transmission electron microscopy, Brunauer-Emmett-Teller surface area,
thermogravimetric analysis, Fourier transform infrared spectroscopy, scanning
electron microscope, and water contact angle. Platelet adhesion and aggregation,
whole blood contact test, hemolysis and related morphology test of red blood
cells, in vitro clotting time tests, and bacterial adhesion assay were performed
to evaluate the anticoagulant effect and the ability of resisting bacterial
adhesion of the modified silicone films. Results indicated that silicone films
modified by MSNs had a good anticoagulant effect and could resist bacterial
adhesion. The modified silicone films have potential as blood-contacting
biomaterials that were attributed to their biomedical properties.
PMID- 28498662
TI - Submolecular Gates Self-Assemble for Hot-Electron Transfer in Proteins.
AB - Redox reactions play key roles in fundamental biological processes. The related
spatial organization of donors and acceptors is assumed to undergo evolutionary
optimization facilitating charge mobilization within the relevant biological
context. Experimental information from submolecular functional sites is needed to
understand the organization strategies and driving forces involved in the self
development of structure-function relationships. Here we exploit chemically
resolved electrical measurements (CREM) to probe the atom-specific electrostatic
potentials (ESPs) in artificial arrays of bacteriochlorophyll (BChl) derivatives
that provide model systems for photoexcited (hot) electron donation and
withdrawal. On the basis of computations we show that native BChl's in the
photosynthetic reaction center (RC) self-assemble at their ground-state as
aligned gates for functional charge transfer. The combined computational and
experimental results further reveal how site-specific polarizability
perpendicular to the molecular plane enhances the hot-electron transport. Maximal
transport efficiency is predicted for a specific, ~5 A, distance above the center
of the metalized BChl, which is in remarkably close agreement with the distance
and mutual orientation of corresponding native cofactors. These findings provide
new metrics and guidelines for analysis of biological redox centers and for
designing charge mobilizing machines such as artificial photosynthesis.
PMID- 28498664
TI - Atmospheric Aqueous Aerosol Surface Tensions: Isotherm-Based Modeling and
Biphasic Microfluidic Measurements.
AB - Surface properties of atmospheric aerosol particles are crucial for accurate
assessments of the fates of liquid particles in the atmosphere. Surface tension
directly influences predictions of particle activation to clouds, as well as
indirectly acting as a proxy for chemical surface partitioning. Challenges to
accounting for surface effects arise from surface tension dependence on solution
concentration and the presence of complex aqueous mixtures in aerosols, including
both surface-active organic solutes and inorganic electrolytes. Also, the
interface itself is varied, in that it may be a liquid-vapor interface, as in the
surface of an aerosol particle with ambient air, or a liquid-liquid interface
between two immiscible liquids, as in the interior surfaces that exist in
multiphase particles. In this Feature Article, we highlight our previous work
entailing thermodynamic modeling of liquid-vapor surfaces to predict surface
tension and microscopic examinations of liquid-liquid interfacial phenomena to
measure interfacial tension using biphasic microscale flows. New results are
presented for binary aqueous organic acids and their ternary solutions with
ammonium sulfate. Ultimately, improved understanding of aerosol particle surfaces
would enhance treatment of aerosol particle-to-cloud activation states and
aerosol effects on climate.
PMID- 28498663
TI - Development of a Multiphysics Model to Characterize the Responsive Behavior of
Magnetic-Sensitive Hydrogels with Finite Deformation.
AB - A novel multiphysics model is developed in this paper for simulation of the
responsive behavior of the magnetic-sensitive hydrogel, with the effects of
magneto-chemo-mechanical coupled fields, which is termed the multi-effect
coupling magnetic-stimulus (MECm) model. In this work, the magnetic
susceptibility for magnetization of the general magnetic hydrogel is defined as a
function of finite deformation, instead of a constant for an ideal magnetic
hydrogel. The present constitutive equations, formulated by the second law of
thermodynamics, account for the effects of the chemical potential, the externally
applied magnetic field, and the finite deformation. In particular, a novel free
energy density is proposed with consideration of the magnetic effect associated
with finite deformation, instead of volume fraction. After examination with
published experimental data, it is confirmed that the MECm model can well capture
the responsive behavior of the magnetic hydrogel, including the deformation and
its instability and hysteresis under a uniform or nonuniform magnetic field. The
parameter studies are then carried out for influences of the magnetic and
geometric properties, including the magnetic intensity, shear modulus, and volume
fraction of the magnetic particles, on the behavior of the magnetic hydrogel, for
a deeper insight into the fundamental mechanism of the magnetic hydrogels.
PMID- 28498665
TI - Iron Phosphate Catalyzed Asymmetric Cross-Dehydrogenative Coupling of 2-Naphthols
with beta-Ketoesters.
AB - Chiral iron phosphate complexes were successfully exploited for asymmetric cross
dehydrogenative coupling reactions between 2-naphthols and beta-ketoester
derivatives. On the basis of kinetic studies, it is suggested that iron
monophosphate complexes constitute the active catalysts that induce
stereoselectivity during the carbon-carbon bond-formation step.
PMID- 28498666
TI - Full-Dimensional Theory of Pair-Correlated HNCO Photofragmentation.
AB - Full-dimensional semiclassical dynamical calculations combining classical paths
and Bohr quantization of product internal motions are reported for the prototype
photofragmentation of isocyanic acid in the S1 state. These calculations allow
one to closely reproduce for the first time key features of state-of-the-art
imaging measurements at photolysis wavelengths of 201 and 210 nm while providing
insight into the underlying dissociation mechanism. Quantum scattering
calculations being beyond reach for most polyatomic fissions, pair-correlated
data on these processes are much more often measured than predicted. Our
theoretical approach can be used to fill this gap.
PMID- 28498667
TI - Oxidative Addition Complexes as Precatalysts for Cross-Coupling Reactions
Requiring Extremely Bulky Biarylphosphine Ligands.
AB - In this report, we describe the application of palladium-based oxidative addition
complexes (OACs) as effective precatalysts for C-N, C-O, and C-F cross-coupling
reactions with a variety of (hetero)arenes. These complexes offer a convenient
alternative to previously developed classes of precatalysts, particularly in the
case of the bulkiest biarylphosphine ligands, for which palladacycle-based
precatalysts do not readily form. The precatalysts described herein are easily
prepared and stable to long-term storage under air.
PMID- 28498668
TI - Kinetics of the Reactions of NO3 Radical with Methacrylate Esters.
AB - Two different experimental methods (relative rate and absolute rate methods) were
used to measure the rate coefficients for the reactions of NO3 radical with six
methacrylate esters: methyl methacrylate (MMA, k1), ethyl methacrylate (EMA, k2),
propyl methacrylate (PMA, k3), isopropyl methacrylate (IPMA, k4), butyl
methacrylate (BMA, k5), and isobutyl methacrylate (IBMA, k6). In the relative
rate method, the loss of the esters relative to that of a reference compound was
followed in a 7300 L Teflon-walled chamber at 298 +/- 2 K and 1000 +/- 5 hpa. In
the absolute method, the temporal profiles of NO3 and N2O5 were followed by using
a dual channel cavity ring-down spectrometer in the presence of an excess of
ester in the 7300 L chamber. The rate coefficients from these two methods
(weighted averages) in the units of 10-15 cm3 molecule-1 s-1 at 298 K are k1 =
2.98 +/- 0.35, k2 = 4.67 +/- 0.49, k3 = 5.23 +/- 0.60, k4 = 7.91 +/- 1.00, k5 =
5.91 +/- 0.58, and k6 = 6.24 +/- 0.66. The quoted uncertainties are at the 2sigma
level and include estimated systematic errors. Unweighted averages are also
reported. In addition, the rate coefficient k7 for the reaction of NO3 radical
with deuterated methyl methacrylate (MMA-d8) was measured by using the relative
rate method to be essentially the same as k1. The trends in the measured rate
coefficient with the length and nature of the alkyl group, along with the
equivalence of k1 and k7, strongly suggest that the reaction of NO3 with the
methacrylate esters proceeds via addition to the double bond on the methacrylate
group. The present results are compared with those from previous studies. Using
the measured values of the rate coefficients, along with those for reactions of
these esters with OH, O3, and chlorine atoms, we calculated the atmospheric
lifetimes of methacrylate esters. We suggest that NO3 radicals do contribute to
the atmospheric loss of these unsaturated esters, but to a lesser extent than
their reactions with OH and O3.
PMID- 28498669
TI - Multiscale Model for Electrokinetic Transport in Networks of Pores, Part I: Model
Derivation.
AB - We present an efficient and robust numerical model for the simulation of
electrokinetic phenomena in porous media and microstructure networks considering
a wide range of applications including energy conversion, deionization, and
microfluidic-based lab-on-a-chip systems. Coupling between fluid flow and ion
transport in these networks is governed by the Poisson-Nernst-Planck-Stokes
equations. These equations describe a wide range of phenomena that can interact
in a complex fashion when coupled in networks involving multiple pores with
variable properties. Capturing these phenomena by direct simulation of the
governing equations in multidimensions is prohibitively expensive. We present
here a reduced-order model that treats a network of many pores via solutions to
1D equations. Assuming that each pore in the network is long and thin, we derive
a 1D model describing the transport in the pore's longitudinal direction. We take
into account the cross-sectional nonuniformity of potential and ion concentration
fields in the form of area-averaged coefficients in different flux terms
representing fluid flow, electric current, and ion fluxes. These coefficients are
obtained from the solutions to the Poisson-Boltzmann equation and are tabulated
against dimensionless surface charge and dimensionless thickness of the electric
double layer (EDL). Although similar models have been attempted in the past,
distinct advantages of the present framework include a fully conservative
discretization with zero numerical leakage, fully bounded area-averaged
coefficients without any singularity in the limit of infinitely thick EDLs, a
flux discretization that exactly preserves equilibrium conditions, and extension
to a general network of pores with multiple intersections. In part II of this two
article series, we present a numerical implementation of this model and
demonstrate its applications in predicting a wide range of electrokinetic
phenomena in microstructures.
PMID- 28498670
TI - Palladium-Catalyzed Aminocarbonylation in Solid-Phase Peptide Synthesis: A Method
for Capping, Cyclization, and Isotope Labeling.
AB - A new synthetic approach for introducing N-capping groups onto peptides attached
to a solid support, combining aminocarbonylation under mild conditions using a
palladacycle precatalyst and solid-phase peptide synthesis, is reported. The use
of a silacarboxylic acid as an in situ CO-releasing molecule allowed the reaction
to be performed in a single vial. The method also enables versatile substitution
of side chains, side-chain-to-side-chain cyclizations, and selective [13C] acyl
labeling of modified peptides.
PMID- 28498671
TI - Correction to "Lanesoic Acid: A Cytotoxic Zwitterion from Theonella sp."
PMID- 28498672
TI - Photovoltaic Hybrid Perovskites under Pressure.
AB - High-pressure studies on methylammonium trihaloplumbates, of general formula
[CH3NH3]+PbX3- (abbreviated MAPbX3, where X = Cl, Br, I), and its analogues shed
new light on the materials for harvesting solar energy and open new perspectives
for photovoltaic science and technology. However, there are considerable
discrepancies between the reported structural, calorimetric, and spectroscopic
results and even between the results obtained by the same technique, for example,
of X-ray diffraction. The origins of these discrepancies and possible pitfalls in
the diffraction and spectroscopic studies on MAPbX3 crystals have been
investigated. Several new effects revealed in this study involve phase
transitions of exceptionally slow kinetics and the coexistence of phases. They
strongly affect photovoltaic properties and are essential for theory,
predictions, and technological applications.
PMID- 28498673
TI - Single Particle Dynamics at the Intrinsic Surface of Various Apolar, Aprotic
Dipolar, and Hydrogen Bonding Liquids As Seen from Computer Simulations.
AB - We investigate the single molecule dynamics at the intrinsic liquid/vapor
interface of five different molecular liquids (carbon tetrachloride, acetone,
acetonitrile, methanol, and water). After assessing that the characteristic
residence times in the surface layer are long enough for a meaningful definition
of several transport properties within the layer itself, we characterize the
dynamics of the individual molecules at the liquid surface by analyzing their
normal and lateral mean-square displacements and lateral velocity autocorrelation
functions and, in the case of the hydrogen bonding liquids (i.e., water and
methanol), also the properties of the hydrogen bonds. Further, dynamical
properties as well as the clustering of the molecules residing unusually long in
the surface layer are also investigated. The global picture emerging from this
analysis is that of a noticeably enhanced dynamics of the molecules at the liquid
surface, with diffusion coefficients up to 4 times larger than in the bulk, and
the disappearance of the caging effect at the surface of all liquids but water.
The dynamics of water is dominated by the strong hydrogen bonding structure also
at the liquid surface.
PMID- 28498674
TI - Anisotropic Fe3O4/Mn3O4 Hybrid Nanocrystals with Unique Magnetic Properties.
AB - This work explores novel nanomagnets by site- and facet-selective epitaxy of
Mn3O4 nanodomains onto colloidal Fe3O4 nanoprisms in solution. At 190 degrees C,
the Mn3O4 nanodomains epitaxially grow at three vertexes of the Fe3O4 nanoprisms
in solution and form horns-on-prism hybrid nanocrystals. At 240 degrees C and in
the same reaction solution, the epitaxy occurs on the top facet of the Fe3O4
nanoprisms, which results in prism-on-prism hybrid nanocrystals. As the
temperature increases from 190 to 240 degrees C, the ratio between the prism-on
prism and horns-on-prism nanocrystals increases. A possible formation mechanism
of Fe3O4/Mn3O4 hybrid nanocrystals is proposed. Novel magnetic behaviors, such as
compensation point, large positive (or negative) exchange bias, and unusual
hysteresis loop character (constricted at low field and expanded at high field),
have been observed for both types of anisotropic hybrid nanomagnets. These unique
magnetic properties are consistent with controlled switch of relative
magnetization orientations between Fe3O4 and Mn3O4 nanodomains from parallel to
antiparallel exchange-coupled configurations.
PMID- 28498675
TI - Explicit Solvent Hydration Benchmark for Proteins with Application to the PBSA
Method.
AB - Explicit and implicit solvent models have a proven record of delivering hydration
free energies of small, druglike solutes in reasonable agreement with experiment.
Hydration of macromolecules, such as proteins, is to a large extent uncharted
territory, with few results shedding light on quantitative consistency between
different solvent models, let alone their ability to reproduce real water. In
this work, based on extensive explicit solvent simulations employing TIP3P and
SPC/E water models we analyze hydration free energy changes between fixed
conformations of 5 diverse proteins, including large multidomain structures. For
the two solvent models we find better agreement in electrostatic rather than
nonpolar contributions (RMSE of 2.3 and 2.7 kcal/mol, respectively), even though
absolute values of the latter are typically an order of magnitude smaller. We
also highlight the importance of finite size corrections to relative protein
hydration free energies, which turn out to be rather large, on the order of
several kcal/mol, and are necessary for proper interpretation of results obtained
under periodic boundary conditions. We further compare gathered data with
predictions of the implicit solvent approach based on the Poisson equation and
the surface or volume based nonpolar term. We find definitely lesser consistency
than between the two explicit models (RMSE between implicit and TIP3 results of
11.3 and 8.4 kcal/mol for electrostatic and nonpolar contributions,
respectively). In the process we determine the value of the protein dielectric
constant and the geometric model for the dielectric boundary that provide for the
best agreement. Finally, we evaluate the usefulness of surface and volume based
models of nonpolar contributions to hydration free energy of large biomolecules.
PMID- 28498676
TI - Intermolecular Interactions in Highly Disordered, Confined Dense N2.
AB - Molecular nitrogen is a benchmark system for condensed matter and, in particular,
for looking at universal properties of strongly confined dense systems. We
conducted Raman and X-ray diffraction measurements on a dense and disordered form
of molecular nitrogen subnanoconfined in a noncatalytic pure SiO2 zeolite under
pressure, up to 50 GPa. In this form, N2-N2 interactions and, consequently,
distances are found to be very close to those of bulk N2 and intramolecular
interactions progressively weaken upon increasing pressure. Surprisingly, the
filled zeolite is still crystalline at 50 GPa with silicon in tetrahedral
coordination by oxygen, which is a record pressure for this type of coordination
among all the known forms of silica. We have thus found a rationale for the
polymerization of a number molecules occurring in the microchannels of
noncatalytic zeolites under pressure, where the pressure threshold is found to be
very similar to that observed in bulk samples.
PMID- 28498677
TI - Radical Cation Cyclopropanations via Chromium Photooxidative Catalysis.
AB - The chromium photocatalyzed cyclopropanation of diazo reagents with electron-rich
alkenes is described. The transformation occurs under mild conditions and
features specific distinctions from traditional diazo-based cyclopropanations
(e.g., avoiding beta-hydride elimination, chemoselectivity considerations, etc.).
The reaction appears to work most effectively using chromium catalysis, and a
number of decorated cyclopropanes can be accessed in generally good yields.
PMID- 28498678
TI - Mechanisms and Origins of Chemo- and Regioselectivities of Ru(II)-Catalyzed
Decarboxylative C-H Alkenylation of Aryl Carboxylic Acids with Alkynes: A
Computational Study.
AB - The mechanisms and chemo- and regioselectivities of Ru(II)-catalyzed
decarboxylative C-H alkenylation of aryl carboxylic acids with alkynes were
investigated with density functional theory (DFT) calculations. The catalytic
cycle involves sequential carboxylate-directed C-H activation, alkyne insertion,
decarboxylation and protonation. The facile tether-assisted decarboxylation step
directs the intermediate toward the desired decarboxylative alkenylation, instead
of typical annulation and double alkenylation pathways. The decarboxylation
barrier is very sensitive to the tether length, and only the seven-membered ring
intermediate can selectively undergo the designed decarboxylation, suggesting a
tether-dependent chemoselectivity. This tether-dependent chemoselectivity also
applies to the alkyl tethers. In addition, the polarity of solvent is found to
control the chemoselectivity between the decarboxylative alkenylation and [4 + 2]
annulation. Solvent with low polarity (toluene) favors the decarboxylation
pathway, leading to the decarboxylative alkenylation. Solvent with high polarity
(methanol) favors the ionic stepwise C-O reductive elimination pathway, leading
to the [4 + 2] annulation. To understand the origins of regioselectivity with
asymmetric alkynes, the distortion/interaction analysis was applied to the alkyne
insertion transition states, and led to a predictive frontier molecular orbital
model. The asymmetric alkynes selectively use the terminal with the larger HOMO
orbital coefficient to form the C-C bond in the insertion step.
PMID- 28498680
TI - Spontaneous Orbital-Selective Mott Transitions and the Jahn-Teller Metal of
A_{3}C_{60}.
AB - The alkali-doped fullerides A_{3}C_{60} are half-filled three-orbital Hubbard
systems which exhibit an unconventional superconducting phase next to a Mott
insulator. While the pairing is understood to arise from an effectively negative
Hund coupling, the highly unusual Jahn-Teller metal near the Mott transition,
featuring both localized and itinerant electrons, has not been understood. This
property is consistently explained by a previously unrecognized phenomenon: the
spontaneous transition of multiorbital systems with negative Hund coupling into
an orbital-selective Mott state. This symmetry-broken state, which has no
ordinary orbital moment, is characterized by an orbital-dependent two-body
operator (the double occupancy) or an orbital-dependent kinetic energy and may be
regarded as a diagonal-order version of odd-frequency superconductivity. We
propose that the recently discovered Jahn-Teller metal phase of Rb_{x}Cs_{3
x}C_{60} is an experimental realization of this novel state of matter.
PMID- 28498679
TI - Observation of the Isovector Giant Monopole Resonance via the
^{28}Si(^{10}Be,^{10}B^{*}[1.74 MeV]) Reaction at 100 AMeV.
AB - The (^{10}Be,^{10}B^{*}[1.74 MeV]) charge-exchange reaction at 100 AMeV is
presented as a new probe for isolating the isovector (DeltaT=1) nonspin-transfer
(DeltaS=0) response of nuclei, with ^{28}Si being the first nucleus studied. By
using a secondary ^{10}Be beam produced by fast fragmentation of ^{18}O nuclei at
the NSCL Coupled Cyclotron Facility, applying the dispersion-matching technique
with the S800 magnetic spectrometer to determine the excitation energy in
^{28}Al, and performing high-resolution gamma-ray tracking with the Gamma-Ray
Energy Tracking In-beam Nuclear Array (GRETINA) to identify the 1022-keV gamma
ray associated with the decay from the 1.74-MeV T=1 isobaric analog state in
^{10}B, a DeltaS=0 excitation-energy spectrum in ^{28}Al was extracted. Monopole
and dipole contributions were determined through a multipole-decomposition
analysis, and the isovector giant dipole resonance and isovector giant monopole
resonance (IVGMR) were identified. The results show that this probe is a powerful
tool for studying the elusive IVGMR, which is of interest for performing
stringent tests of modern density functional theories at high excitation energies
and for constraining the bulk properties of nuclei and nuclear matter. The
extracted distributions were compared with theoretical calculations based on the
normal-modes formalism and the proton-neutron relativistic time-blocking
approximation. Calculated cross sections based on these strengths underestimate
the data by about a factor of 2, which likely indicates deficiencies in the
reaction calculations based on the distorted wave Born approximation.
PMID- 28498681
TI - Bound States and Field-Polarized Haldane Modes in a Quantum Spin Ladder.
AB - The challenge of one-dimensional systems is to understand their physics beyond
the level of known elementary excitations. By high-resolution neutron
spectroscopy in a quantum spin-ladder material, we probe the leading
multiparticle excitation by characterizing the two-magnon bound state at zero
field. By applying high magnetic fields, we create and select the singlet
(longitudinal) and triplet (transverse) excitations of the fully spin-polarized
ladder, which have not been observed previously and are close analogs of the
modes anticipated in a polarized Haldane chain. Theoretical modeling of the
dynamical response demonstrates our complete quantitative understanding of these
states.
PMID- 28498682
TI - Searching for Axionlike Particles with Ultraperipheral Heavy-Ion Collisions.
AB - We show that ultraperipheral heavy-ion collisions at the Large Hadron Collider
(LHC) can be used to search for axionlike particles with mass below 100 GeV. The
Z^{4} enhanced photon-photon luminosity from the ions provides a large exclusive
production rate, with a signature of a resonant pair of back-to-back photons and
no other activity in the detector. In addition, we present both new and updated
limits from recasting multiphoton searches at LEP II and the LHC, which are more
stringent than those currently in the literature for the mass range 100 MeV to
100 GeV.
PMID- 28498683
TI - Probing CP Violation in h->tau^{-}tau^{+} at the LHC.
AB - We propose a novel method to reconstruct event by event the full kinematics of
the cascade decay process, h->tau^{+}tau^{-}->(pi^{+}nu[over -])(pi^{-}nu), which
allows us to measure the tau^{+}tau^{-} spin correlation, a measure of the CP
property of the Higgs boson. By noting that the tau^{+/-} momenta lie on the
plane spanned by the accurately measured impact parameter and momentum vectors of
charged pions, we can obtain the most likely momenta of the two missing neutrinos
by using the probability distribution functions of the p[over ->]_{T} vector and
the location of the primary vertex. A simple detector level simulation shows an
excellent agreement between the reconstructed and the true kinematics, both in
the tau^{+}tau^{-} and the pi^{+}pi^{-} rest frames. The method can be tested in
Z->tau^{+}tau^{-} events, which should exhibit no correlation.
PMID- 28498684
TI - Giant Thermal Magnetoresistance in Plasmonic Structures.
AB - A giant thermal magnetoresistance is predicted for the electromagnetic transport
of heat in magneto-optical plasmonic structures. In chains of InSb-Ag
nanoparticles at room temperature, we find that the resistance can be increased
by almost a factor of 2 with magnetic fields of 2 T. We show that this important
change results from the strong spectral dependence of localized surface waves on
the magnitude of the magnetic field.
PMID- 28498685
TI - PT-Symmetric Scattering in Flow Duct Acoustics.
AB - We show theoretically and experimentally that the propagation of an acoustic wave
in an airflow duct going through a pair of diaphragms, with equivalent amounts of
mean-flow-induced effective gain and loss, displays all the features of a parity
time (PT) symmetric system. Using a scattering matrix formalism, we observe,
experimentally, the properties which reflect the PT symmetry of the scattering
acoustical system: the existence of spontaneous symmetry breaking with symmetry
broken pairs of scattering eigenstates showing amplification and reduction, and
the existence of points with unidirectional invisibility.
PMID- 28498687
TI - Effect of Compactified Dimensions and Background Magnetic Fields on the Phase
Structure of SU(N) Gauge Theories.
AB - We discuss the properties of non-Abelian gauge theories formulated on manifolds
with compactified dimensions and in the presence of fermionic fields coupled to
magnetic backgrounds. We show that different phases may emerge, corresponding to
different realizations of center symmetry and translational invariance, depending
on the compactification radius and on the magnitude of the magnetic field. Our
discussion then focuses on the case of an SU(3) gauge theory in four dimensions
with fermions fields in the fundamental representation, for which we provide some
exploratory numerical lattice results.
PMID- 28498686
TI - Intense-Laser Solid State Physics: Unraveling the Difference between
Semiconductors and Dielectrics.
AB - Experiments on intense laser driven dielectrics have revealed population transfer
to the conduction band to be oscillatory in time. This is in stark contrast to
ionization in semiconductors and is currently unexplained. Current ionization
theories neglect coupling between the valence and conduction band and therewith,
the dynamic Stark shift. Our single-particle analysis identifies this as a
potential reason for the different ionization behavior. The dynamic Stark shift
increases the band gap with increasing laser intensities, thus suppressing
ionization to an extent where virtual population oscillations become dominant.
The dynamic Stark shift plays a role dominantly in dielectrics which, due to the
larger band gap, can be exposed to significantly higher laser intensities.
PMID- 28498688
TI - Antiferromagnetic Correlations in Two-Dimensional Fermionic Mott-Insulating and
Metallic Phases.
AB - We experimentally study the emergence of antiferromagnetic correlations between
ultracold fermionic atoms in a two-dimensional optical lattice with decreasing
temperature. We determine the uniform magnetic susceptibility of the two
dimensional Hubbard model from simultaneous measurements of the in situ density
distribution of both spin components. At half filling and strong interactions our
data approach the Heisenberg model of localized spins with antiferromagnetic
correlations. Moreover, we observe a fast decay of magnetic correlations when
doping the system away from half filling.
PMID- 28498689
TI - Evidence for a Nematic Phase in La_{1.75}Sr_{0.25}NiO_{4}.
AB - Determining the nature of electronic states in doped Mott insulators remains a
challenging task. In the case of tetragonal La_{2-x}Sr_{x}NiO_{4}, the occurrence
of diagonal charge and spin stripe order in the ground state is now well
established. In contrast, the nature of the high-temperature "disordered" state
from which the stripe order develops has long been a subject of controversy, with
considerable speculation regarding a polaronic liquid. Following the recent
detection of dynamic charge stripes, we use neutron scattering measurements on an
x=0.25 crystal to demonstrate that the dispersion of the charge-stripe
excitations is anisotropic. This observation provides compelling evidence for the
presence of electronic nematic order.
PMID- 28498690
TI - Nonexponential Decoherence and Subdiffusion in Atom-Optics Kicked Rotor.
AB - Quantum systems lose coherence upon interaction with the environment and tend
towards classical states. Quantum coherence is known to exponentially decay in
time so that macroscopic quantum superpositions are generally unsustainable. In
this work, slower than exponential decay of coherences is experimentally realized
in an atom-optics kicked rotor system subjected to nonstationary Levy noise in
the applied kick sequence. The slower coherence decay manifests in the form of
quantum subdiffusion that can be controlled through the Levy exponent. The
experimental results are in good agreement with the analytical estimates and
numerical simulations for the mean energy growth and momentum profiles of an atom
optics kicked rotor.
PMID- 28498691
TI - Electron-Scale Quadrants of the Hall Magnetic Field Observed by the
Magnetospheric Multiscale spacecraft during Asymmetric Reconnection.
AB - An in situ measurement at the magnetopause shows that the quadrupole pattern of
the Hall magnetic field, which is commonly observed in a symmetric reconnection,
is still evident in an asymmetric component reconnection, but the two quadrants
adjacent to the magnetosphere are strongly compressed into the electron scale and
the widths of the remaining two quadrants are still ion scale. The bipolar Hall
electric field pattern generally created in a symmetric reconnection is replaced
by a unipolar electric field within the electron-scale quadrants. Furthermore, it
is concluded that the spacecraft directly passed through the inner electron
diffusion region based on the violation of the electron frozen-in condition, the
energy dissipation, and the slippage between the electron flow and the magnetic
field. Within the inner electron diffusion region, magnetic energy was released
and accumulated simultaneously, and it was accumulated in the perpendicular
directions while dissipated in the parallel direction. The localized thinning of
the current sheet accounts for the energy accumulation in a reconnection.
PMID- 28498692
TI - Ideal Magnetic Dipole Scattering.
AB - We introduce the concept of tunable ideal magnetic dipole scattering, where a
nonmagnetic nanoparticle scatters light as a pure magnetic dipole. High
refractive index subwavelength nanoparticles usually support both electric and
magnetic dipole responses. Thus, to achieve ideal magnetic dipole scattering one
has to suppress the electric dipole response. Such a possibility was recently
demonstrated for the so-called anapole mode, which is associated with zero
electric dipole scattering. By spectrally overlapping the magnetic dipole
resonance with the anapole mode, we achieve ideal magnetic dipole scattering in
the far field with tunable strong scattering resonances in the near infrared
spectrum. We demonstrate that such a condition can be realized at least for two
subwavelength geometries. One of them is a core-shell nanosphere consisting of a
Au core and silicon shell. It can be also achieved in other geometries, including
nanodisks, which are compatible with current nanofabrication technology.
PMID- 28498693
TI - Publisher's Note: Probing the Scale Invariance of the Inflationary Power Spectrum
in Expanding Quasi-Two-Dimensional Dipolar Condensates [Phys. Rev. Lett. 118,
130404 (2017)].
AB - This corrects the article DOI: 10.1103/PhysRevLett.118.130404.
PMID- 28498694
TI - Spectrum of the Nuclear Environment for GaAs Spin Qubits.
AB - Using a singlet-triplet spin qubit as a sensitive spectrometer of the GaAs
nuclear spin bath, we demonstrate that the spectrum of Overhauser noise agrees
with a classical spin diffusion model over 6 orders of magnitude in frequency,
from 1 mHz to 1 kHz, is flat below 10 mHz, and falls as 1/f^{2} for frequency f?1
Hz. Increasing the applied magnetic field from 0.1 to 0.75 T suppresses electron
mediated spin diffusion, which decreases the spectral content in the 1/f^{2}
region and lowers the saturation frequency, each by an order of magnitude,
consistent with a numerical model. Spectral content at megahertz frequencies is
accessed using dynamical decoupling, which shows a crossover from the few-pulse
regime (?16pi pulses), where transverse Overhauser fluctuations dominate
dephasing, to the many-pulse regime (?32 pi pulses), where longitudinal
Overhauser fluctuations with a 1/f spectrum dominate.
PMID- 28498695
TI - Ab Initio Green-Kubo Approach for the Thermal Conductivity of Solids.
AB - We herein present a first-principles formulation of the Green-Kubo method that
allows the accurate assessment of the phonon thermal conductivity of solid
semiconductors and insulators in equilibrium ab initio molecular dynamics
calculations. Using the virial for the nuclei, we propose a unique ab initio
definition of the heat flux. Accurate size and time convergence are achieved
within moderate computational effort by a robust, asymptotically exact
extrapolation scheme. We demonstrate the capabilities of the technique by
investigating the thermal conductivity of extreme high and low heat conducting
materials, namely, Si (diamond structure) and tetragonal ZrO_{2}.
PMID- 28498696
TI - Hyperfine and Spin-Orbit Coupling Effects on Decay of Spin-Valley States in a
Carbon Nanotube.
AB - The decay of spin-valley states is studied in a suspended carbon nanotube double
quantum dot via the leakage current in Pauli blockade and via dephasing and
decoherence of a qubit. From the magnetic field dependence of the leakage
current, hyperfine and spin-orbit contributions to relaxation from blocked to
unblocked states are identified and explained quantitatively by means of a simple
model. The observed qubit dephasing rate is consistent with the hyperfine
coupling strength extracted from this model and inconsistent with dephasing from
charge noise. However, the qubit coherence time, although longer than previously
achieved, is probably still limited by charge noise in the device.
PMID- 28498697
TI - Single Nodal Loop of Accidental Degeneracies in Minimal Symmetry: Triclinic
CaAs_{3}.
AB - The existence of closed loops of degeneracies in crystals has been intimately
connected with associated crystal symmetries, raising the following question:
What is the minimum symmetry required for topological character, and can one find
an example? Triclinic CaAs_{3}, in the space group P1[over -] with only a center
of inversion, has been found to display, without need for tuning, a nodal loop of
accidental degeneracies with topological character, centered on one face of the
Brillouin zone that is otherwise fully gapped. The small loop is very flat in
energy, yet is cut four times by the Fermi energy, a condition that results in an
intricate repeated touching of inversion related pairs of Fermi surfaces at Weyl
points. Spin-orbit coupling lifts the fourfold degeneracy along the loop, leaving
trivial Kramers pairs. With its single nodal loop that emerges without protection
from any point group symmetry, CaAs_{3} represents the primal "hydrogen atom" of
nodal loop systems.
PMID- 28498698
TI - Topological Phases of Parafermions: A Model with Exactly Solvable Ground States.
AB - Parafermions are emergent excitations that generalize Majorana fermions and can
also realize topological order. In this Letter, we present a nontrivial and quasi
exactly-solvable model for a chain of parafermions in a topological phase. We
compute and characterize the ground-state wave functions, which are matrix
product states and have a particularly elegant interpretation in terms of Fock
parafermions, reflecting the factorized nature of the ground states. Using these
wave functions, we demonstrate analytically several signatures of topological
order. Our study provides a starting point for the nonapproximate study of
topological one-dimensional parafermionic chains with spatial inversion and time
reversal symmetry in the absence of strong edge modes.
PMID- 28498699
TI - Interaction-Driven Shift and Distortion of a Flat Band in an Optical Lieb
Lattice.
AB - We report the momentum-resolved measurement of Bloch bands in an optical Lieb
lattice for a Bose-Einstein condensate (BEC). A BEC in the lattice is transported
to a desired quasimomentum by applying a constant force. The energy dispersion of
the lowest band is obtained by integrating measured group velocities. We also
measure the gap from the lowest band to the higher bands with the same
quasimomentum, which can be extracted from the oscillation of the sublattice
populations after preparing a superposition of the band eigenstates. We show that
the experimental results agree with a band calculation based on the Bogoliubov
approximation. It is revealed that the second band, which should be flat in a
single-particle description, is shifted and, in particular, distorted around the
Brillouin zone edge as the interaction strength increases.
PMID- 28498700
TI - Antiferroquadrupolar Order and Rotational Symmetry Breaking in a Generalized
Bilinear-Biquadratic Model on a Square Lattice.
AB - The magnetic and nematic properties of the iron chalcogenides have recently been
the subject of intense interest. Motivated by the proposed antiferroquadrupolar
and Ising-nematic orders for the bulk FeSe, we study the phase diagram of an S=1
generalized bilinear-biquadratic model with multineighbor interactions. We find a
large parameter regime for a (pi, 0) antiferroquadrupolar phase, showing how
quantum fluctuations stabilize it by lifting an infinite degeneracy of certain
semiclassical states. Evidence for this C_{4}-symmetry-breaking quadrupolar phase
is also provided by an unbiased density matrix renormalization group analysis. We
discuss the implications of our results for FeSe and related iron-based
superconductors.
PMID- 28498701
TI - Fast Low-to-High Confinement Mode Bifurcation Dynamics in a Tokamak Edge Plasma
Gyrokinetic Simulation.
AB - Transport barrier formation and its relation to sheared flows in fluids and
plasmas are of fundamental interest in various natural and laboratory
observations and of critical importance in achieving an economical energy
production in a magnetic fusion device. Here we report the first observation of
an edge transport barrier formation event in an electrostatic gyrokinetic
simulation carried out in a realistic diverted tokamak edge geometry under strong
forcing by a high rate of heat deposition. The results show that turbulent
Reynolds-stress-driven sheared E*B flows act in concert with neoclassical orbit
loss to quench turbulent transport and form a transport barrier just inside the
last closed magnetic flux surface.
PMID- 28498702
TI - Anomalous de Haas-van Alphen Effect in InAs/GaSb Quantum Wells.
AB - The de Haas-van Alphen effect describes the periodic oscillation of the
magnetization in a material as a function of an inverse applied magnetic field.
It forms the basis of a well established procedure for measuring Fermi surface
properties, and its observation is typically taken as a direct signature of a
system being metallic. However, certain insulators can show similar oscillations
of the magnetization from quantization of the energies of electron states in
filled bands. Recently, the theory of such an anomalous dHvAE (AdHvAE) was worked
out, but there has not yet been a clear experimental observation. Here, we show
that the inverted narrow gap regime of InAs/GaSb quantum wells is an ideal
platform for the observation of the AdHvAE. From our microscopic calculations, we
make quantitative predictions for the relevant magnetic field and temperature
regimes, and we describe unambiguous experimental signatures.
PMID- 28498703
TI - Realization of a Cascaded Quantum System: Heralded Absorption of a Single Photon
Qubit by a Single-Electron Charged Quantum Dot.
AB - Photonic losses pose a major limitation for the implementation of a quantum state
transfer between nodes of a quantum network. A measurement that heralds a
successful transfer without revealing any information about the qubit may
alleviate this limitation. Here, we demonstrate the heralded absorption of a
single photonic qubit, generated by a single neutral quantum dot, by a single
electron charged quantum dot that is located 5 m away. The transfer of quantum
information to the spin degree of freedom takes place upon the emission of a
photon; for a properly chosen or prepared quantum dot, the detection of this
photon yields no information about the qubit. We show that this process can be
combined with local operations optically performed on the destination node by
measuring classical correlations between the absorbed photon color and the final
state of the electron spin. Our work suggests alternative avenues for the
realization of quantum information protocols based on cascaded quantum systems.
PMID- 28498704
TI - Slip Morphology of Elastic Strips on Frictional Rigid Substrates.
AB - The morphology of an elastic strip subject to vertical compressive stress on a
frictional rigid substrate is investigated by a combination of theory and
experiment. We find a rich variety of morphologies, which-when the bending
elasticity dominates over the effect of gravity-are classified into three
distinct types of states: pinned, partially slipped, and completely slipped,
depending on the magnitude of the vertical strain and the coefficient of static
friction. We develop a theory of elastica under mixed clamped-hinged boundary
conditions combined with the Coulomb-Amontons friction law and find excellent
quantitative agreement with simulations and controlled physical experiments. We
also discuss the effect of gravity in order to bridge the difference in the
qualitative behaviors of stiff strips and flexible strings or ropes. Our study
thus complements recent work on elastic rope coiling and takes a significant step
towards establishing a unified understanding of how a thin elastic object
interacts vertically with a solid surface.
PMID- 28498705
TI - Incoherence-Mediated Remote Synchronization.
AB - In previously identified forms of remote synchronization between two nodes, the
intermediate portion of the network connecting the two nodes is not synchronized
with them but generally exhibits some coherent dynamics. Here we report on a
network phenomenon we call incoherence-mediated remote synchronization (IMRS), in
which two noncontiguous parts of the network are identically synchronized while
the dynamics of the intermediate part is statistically and information
theoretically incoherent. We identify mirror symmetry in the network structure as
a mechanism allowing for such behavior, and show that IMRS is robust against
dynamical noise as well as against parameter changes. IMRS may underlie neuronal
information processing and potentially lead to network solutions for encryption
key distribution and secure communication.
PMID- 28498706
TI - Sisyphus Laser Cooling of a Polyatomic Molecule.
AB - We perform magnetically assisted Sisyphus laser cooling of the triatomic free
radical strontium monohydroxide (SrOH). This is achieved with principal optical
cycling in the rotationally closed P(N^{''}=1) branch of either the X[over
~]^{2}Sigma^{+}(000)<->A[over ~]^{2}Pi_{1/2}(000) or the X[over
~]^{2}Sigma^{+}(000)<->B[over ~]^{2}Sigma^{+}(000) vibronic transitions.
Molecules lost into the excited vibrational states during the cooling process are
repumped back through the B[over ~](000) state for both the (100) level of the Sr
O stretching mode and the (02^{0}0) level of the bending mode. The transverse
temperature of a SrOH molecular beam is reduced in one dimension by 2 orders of
magnitude to ~750 MUK. This approach opens a path towards creating a variety of
ultracold polyatomic molecules by means of direct laser cooling.
PMID- 28498707
TI - Electronic Phase Separation and Dramatic Inverse Band Renormalization in the
Mixed-Valence Cuprate LiCu_{2}O_{2}.
AB - We measured, by angle-resolved photoemission spectroscopy, the electronic
structure of LiCu_{2}O_{2}, a mixed-valence cuprate where planes of Cu(I)
(3d^{10}) ions are sandwiched between layers containing one-dimensional edge
sharing Cu(II) (3d^{9}) chains. We find that the Cu(I)- and Cu(II)-derived
electronic states form separate electronic subsystems, in spite of being coupled
by bridging O ions. The valence band, of the Cu(I) character, disperses within
the charge-transfer gap of the strongly correlated Cu(II) states, displaying an
unprecedented 250% broadening of the bandwidth with respect to the predictions of
density functional theory. Our observation is at odds with the widely accepted
tenet of many-body theory that correlation effects generally yield narrower bands
and larger electron masses and suggests that present-day electronic structure
techniques provide an intrinsically inappropriate description of ligand-to-d
hybridizations in late transition metal oxides.
PMID- 28498708
TI - Supercurrents in Unidirectional Channels Originate from Information Transfer in
the Opposite Direction: A Theoretical Prediction.
AB - It has been thought that the long chiral edge channels cannot support any
supercurrent between the superconducting electrodes. We show theoretically that
the supercurrent can be mediated by a nonlocal interaction that facilitates a
long-distance information transfer in the direction opposite of electron flow. We
compute the supercurrent for several interaction models, including that of an
external circuit.
PMID- 28498709
TI - Topological Magnon Bands and Unconventional Superconductivity in Pyrochlore
Iridate Thin Films.
AB - We theoretically study the magnetic properties of pyrochlore iridate bilayer and
trilayer thin films grown along the [111] direction using a strong coupling
approach. We find the ground state magnetic configurations on a mean field level
and carry out a spin-wave analysis about them. In the trilayer case the ground
state is found to be the all-in-all-out (AIAO) state, whereas the bilayer has a
deformed AIAO state. For all parameters of the spin-orbit coupled Hamiltonian we
study, the lowest magnon band in the trilayer case has a nonzero Chern number. In
the bilayer case we also find a parameter range with nonzero Chern numbers. We
calculate the magnon Hall response for both geometries, finding a striking sign
change as a function of temperature. Using a slave-boson mean-field theory we
study the doping of the trilayer system and discover an unconventional time
reversal symmetry broken d+id superconducting state. Our study complements prior
work in the weak coupling limit and suggests that the [111] grown thin film
pyrochlore iridates are a promising candidate for topological properties and
unconventional orders.
PMID- 28498711
TI - Projector Quantum Monte Carlo Method for Nonlinear Wave Functions.
AB - We reformulate the projected imaginary-time evolution of the full configuration
interaction quantum Monte Carlo method in terms of a Lagrangian minimization.
This naturally leads to the admission of polynomial complex wave function
parametrizations, circumventing the exponential scaling of the approach. While
previously these functions have traditionally inhabited the domain of variational
Monte Carlo approaches, we consider recent developments for the identification of
deep-learning neural networks to optimize this Lagrangian, which can be written
as a modification of the propagator for the wave function dynamics. We
demonstrate this approach with a form of tensor network state, and use it to find
solutions to the strongly correlated Hubbard model, as well as its application to
a fully periodic ab initio graphene sheet. The number of variables which can be
simultaneously optimized greatly exceeds alternative formulations of variational
Monte Carlo methods, allowing for systematic improvability of the wave function
flexibility towards exactness for a number of different forms, while blurring the
line between traditional variational and projector quantum Monte Carlo
approaches.
PMID- 28498712
TI - Fast Diffusion of Long Guest Rods in a Lamellar Phase of Short Host Particles.
AB - We investigate the dynamic behavior of long guest rodlike particles immersed in
liquid crystalline phases formed by shorter host rods, tracking both guest and
host particles by fluorescence microscopy. Counterintuitively, we evidence that
long rods diffuse faster than short rods forming the one-dimensional ordered
smectic-A phase. This results from the larger and noncommensurate size of the
guest particles as compared to the wavelength of the energy landscape set by the
lamellar stack of liquid slabs. The long guest particles are also shown to be
still mobile in the crystalline smectic-B phase, as they generate their own voids
in the adjacent layers.
PMID- 28498713
TI - Improved Sensing with a Single Qubit.
AB - We consider quantum metrology with arbitrary prior knowledge of the parameter. We
demonstrate that a single sensing two-level system can act as a virtual
multilevel system that offers increased sensitivity in a Bayesian single-shot
metrology scenario, and that allows one to estimate (arbitrary) large parameter
values by avoiding phase wraps. This is achieved by making use of additional
degrees of freedom or auxiliary systems not participating in the sensing process.
The joint system is manipulated by intermediate control operations in such a way
that an effective Hamiltonian, with an arbitrary spectrum, is generated that
mimics the spectrum of a multisystem interacting with the field. We show how to
use additional internal degrees of freedom of a single trapped ion to achieve a
high-sensitivity magnetic field sensor for fields with arbitrary prior knowledge.
PMID- 28498710
TI - Charge-Induced Force Noise on Free-Falling Test Masses: Results from LISA
Pathfinder.
AB - We report on electrostatic measurements made on board the European Space Agency
mission LISA Pathfinder. Detailed measurements of the charge-induced
electrostatic forces exerted on free-falling test masses (TMs) inside the
capacitive gravitational reference sensor are the first made in a relevant
environment for a space-based gravitational wave detector. Employing a
combination of charge control and electric-field compensation, we show that the
level of charge-induced acceleration noise on a single TM can be maintained at a
level close to 1.0 fm s^{-2} Hz^{-1/2} across the 0.1-100 mHz frequency band
that is crucial to an observatory such as the Laser Interferometer Space Antenna
(LISA). Using dedicated measurements that detect these effects in the
differential acceleration between the two test masses, we resolve the stochastic
nature of the TM charge buildup due to interplanetary cosmic rays and the TM
charge-to-force coupling through stray electric fields in the sensor. All our
measurements are in good agreement with predictions based on a relatively simple
electrostatic model of the LISA Pathfinder instrument.
PMID- 28498714
TI - Mitigation of the Hose Instability in Plasma-Wakefield Accelerators.
AB - Current models predict the hose instability to crucially limit the applicability
of plasma-wakefield accelerators. By developing an analytical model which
incorporates the evolution of the hose instability over long propagation
distances, this work demonstrates that the inherent drive-beam energy loss, along
with an initial beam-energy spread, detunes the betatron oscillations of beam
electrons and thereby mitigates the instability. It is also shown that tapered
plasma profiles can strongly reduce initial hosing seeds. Hence, we demonstrate
that the propagation of a drive beam can be stabilized over long propagation
distances, paving the way for the acceleration of high-quality electron beams in
plasma-wakefield accelerators. We find excellent agreement between our models and
particle-in-cell simulations.
PMID- 28498715
TI - Anderson Localization of Ultracold Atoms: Where is the Mobility Edge?
AB - Recent experiments in noninteracting ultracold atoms in three-dimensional speckle
potentials have yielded conflicting results regarding the so-called mobility
edge, i.e., the energy threshold separating Anderson localized from diffusive
states. At the same time, there are theoretical indications that most
experimental data overestimate this critical energy, sometimes by a large amount.
Using extensive numerical simulations, we show that the effect of anisotropy in
the spatial correlations of realistic disorder configurations alone is not
sufficient to explain the experimental data. In particular, we find that the
mobility edge obeys a universal scaling behavior, independently of the speckle
geometry.
PMID- 28498717
TI - Melatonin as a versatile molecule to design novel multitarget hybrids against
neurodegeneration.
AB - Melatonin is an indoleamine produced mainly in the pineal gland. The natural
decline of melatonin levels with aging strongly contributes to the development of
neurodegenerative disorders. Pleiotropic actions displayed by melatonin prevent
several processes involved in neurodegeneration such as neuroinflammation,
oxidative stress, excitotoxicity and/or apoptosis. This review focuses on a
number of melatonin hybrids resulting from the juxtaposition of tacrine,
berberine, tamoxifen, curcumin, N,N-dibenzyl(N-methyl)amine, among others, with
potential therapeutic effects for the treatment of neurodegenerative diseases.
PMID- 28498716
TI - Chronotype distribution in professional rugby players: Evidence for the
environment hypothesis?
AB - Individual sport athletes have been shown to comprise unusually high proportions
of morning-types (MTs) coupled with a higher prevalence of the morningness
associated PERIOD3 variable number tandem repeat (VNTR) allele, PER35. The degree
to which type of sport selected is influenced by either chronotype or genotype,
or the extent to which sporting environment contributes to chronotype is unclear.
The aim of this study was to assess chronotype and PER3 VNTR polymorphism
frequencies in team sport players and non-athletic controls. South African male
Super Rugby players (RUG, n = 120) and a control population of males with
habitually low levels of physical activity (defined as exercise no more than
twice a week; CON, n = 117) took part in this study. Participants completed the
Horne-Ostberg morningness-eveningness questionnaire to determine chronotype and
donated buccal cell or blood samples from which PER3 VNTR genotype was
established. There were more MTs in the RUG (47%) than CON group (23%, p <
0.001), more evening-types in the CON group (18%) compared to the RUG group (3%,
p < 0.001), but no differences in PER3 VNTR genotype (p = 0.619) or allele (p =
0.758) frequencies. In both groups, more people carried the PER34 allele (RUG:
63%, CON: 62%). Chronotype was associated with genotype in the CON (p = 0.004)
but not the RUG group (p = 0.895). Unlike the individual sport endurance athletes
previously studied in whom the PER35 allele predominated, the PER3 VNTR genotype
distribution in these team sport players was similar to that of the general
population. We hypothesise that the absence of any chronotype-genotype
relationship in these rugby players is because their diurnal preference is
shifted towards morningness through habitual athletic behaviour.
PMID- 28498718
TI - Effects of regular cannabis use on neurocognition, brain structure, and function:
a systematic review of findings in adults.
AB - BACKGROUND: Cannabis is the most used illicit drug worldwide. The long-standing
consequences for the central nervous system associated with frequent cannabis use
have not been well delineated and should be determined. OBJECTIVE: To review
recent studies on the effects of regular cannabis use regarding its effects on
cognition, brain structure, and function in adults. METHODS: A systematic
literature review was conducted by performing electronic searches in the PubMed,
LILACS, and SciELO databases (2010-2016). The initial search identified 898
records. They were evaluated for relevance according to the inclusion and
exclusion criteria and 56 studies were included. RESULTS: The neuropsychological
studies provide evidence for subtle cognitive deficits at least 7 days after
heavy cannabis use. The structural neuroimaging studies show growing evidence of
abnormalities in hippocampus volume and gray matter density of cannabis users
relative to controls; however, morphological changes in other brain regions are
more controversial. The functional neuroimaging studies suggest an altered
pattern of brain activity associated with cannabis use. CONCLUSION: Although
there are several limitations for study comparison and substantial heterogeneity
in the findings, the present review suggests that regular cannabis use is
associated with mild cognitive changes in addition to structural and functional
alterations in the brain in adults. The morphological alterations could
ultimately affect brain organization and function, but the associated time course
for neuronal recovery as well as the real impact on cognitive functioning remain
unknown. Also, it is still unclear whether the identified alterations are as a
consequence of or precede cannabis use.
PMID- 28498719
TI - Surgical anatomy of the pelvic vasculature, with particular reference to
acetabular screw fixation in cementless total hip arthroplasty in Asian
population.
AB - PURPOSE: Pelvic vascular injury is a serious complication associated with
acetabular component setting with screw fixation in cementless total hip
arthroplasty (THA). In this study, we investigated the safety zone for acetabular
component setting with screw fixation in cementless THA as a means to prevent
pelvic vascular injury. METHODS: Thirty left hip joints of Japanese cadavers (11
males and 19 females) were analyzed. We used a hemispherical measuring cup with
52 guide holes designed to allow vertical insertion of a Kirschner wire. After
the measuring cup was placed on the acetabulum, the Kirschner wire was inserted
from each guide hole to examine the anatomical relationship between the
acetabulum and the pelvic vessels. We calculated the frequency of pelvic vessel
punctures and measured the distance from the acetabular surface to the pelvic
vessels at each guide hole. RESULTS: Our findings revealed that pelvic vessels do
not exist in certain parts of the posterior area of the acetabulum. Furthermore,
in this area, intrapelvic vessels are either lacking or located at a distance
>=31 mm from the surface of the acetabulum. CONCLUSION: The posterior area of the
acetabulum, excluding its central portion, appeared to be the safety zone for
acetabular screw fixation in Japanese cadavers.
PMID- 28498720
TI - Protein Misfolding, Amyloid Formation, and Human Disease: A Summary of Progress
Over the Last Decade.
AB - Peptides and proteins have been found to possess an inherent tendency to convert
from their native functional states into intractable amyloid aggregates. This
phenomenon is associated with a range of increasingly common human disorders,
including Alzheimer and Parkinson diseases, type II diabetes, and a number of
systemic amyloidoses. In this review, we describe this field of science with
particular reference to the advances that have been made over the last decade in
our understanding of its fundamental nature and consequences. We list the
proteins that are known to be deposited as amyloid or other types of aggregates
in human tissues and the disorders with which they are associated, as well as the
proteins that exploit the amyloid motif to play specific functional roles in
humans. In addition, we summarize the genetic factors that have provided insight
into the mechanisms of disease onset. We describe recent advances in our
knowledge of the structures of amyloid fibrils and their oligomeric precursors
and of the mechanisms by which they are formed and proliferate to generate
cellular dysfunction. We show evidence that a complex proteostasis network
actively combats protein aggregation and that such an efficient system can fail
in some circumstances and give rise to disease. Finally, we anticipate the
development of novel therapeutic strategies with which to prevent or treat these
highly debilitating and currently incurable conditions.
PMID- 28498721
TI - Mechanisms of Deubiquitinase Specificity and Regulation.
AB - Protein ubiquitination is one of the most powerful posttranslational
modifications of proteins, as it regulates a plethora of cellular processes in
distinct manners. Simple monoubiquitination events coexist with more complex
forms of polyubiquitination, the latter featuring many different chain
architectures. Ubiquitin can be subjected to further posttranslational
modifications (e.g., phosphorylation and acetylation) and can also be part of
mixed polymers with ubiquitin-like modifiers such as SUMO (small ubiquitin
related modifier) or NEDD8 (neural precursor cell expressed, developmentally
downregulated 8). Together, cellular ubiquitination events form a sophisticated
and versatile ubiquitin code. Deubiquitinases (DUBs) reverse ubiquitin signals
with equally high sophistication. In this review, we conceptualize the many
layers of specificity that DUBs encompass to control the ubiquitin code and
discuss examples in which DUB specificity has been understood at the molecular
level. We further discuss the many mechanisms of DUB regulation with a focus on
those that modulate catalytic activity. Our review provides a framework to tackle
lingering questions in DUB biology.
PMID- 28498722
TI - Positive affective processes underlie positive health behaviour change.
AB - Positive health behaviours such as physical activity can prevent or reverse many
chronic conditions, yet a majority of people fall short of leading a healthy
lifestyle. Recent discoveries in affective science point to promising approaches
to circumvent barriers to lifestyle change. Here, we present a new theoretical
framework that integrates scientific knowledge about positive affect with that on
implicit processes. The upward spiral theory of lifestyle change explains how
positive affect can facilitate long-term adherence to positive health behaviours.
The inner loop of this spiral model identifies nonconscious motives as a central
mechanism of behavioural maintenance. Positive affect experienced during health
behaviours increases incentive salience for cues associated with those
behaviours, which in turn, implicitly guides attention and the everyday decisions
to repeat those behaviours. The outer loop represents the evidence-backed claim,
based on Fredrickson's broaden-and-build theory, that positive affect builds a
suite of endogenous resources, which may in turn amplify the positive affect
experienced during positive health behaviours and strengthen the nonconscious
motives. We offer published and preliminary evidence in favour of the theory,
contrast it to other dominant theories of health behaviour change, and highlight
attendant implications for interventions that merit testing.
PMID- 28498723
TI - Advances in Preimplantation Genetic Testing for Monogenic Disease and Aneuploidy.
AB - Genetic testing of preimplantation embryos promises to prevent monogenic disease
in children born to at-risk couples, the transfer of unbalanced embryos to
patients carrying a balanced translocation, and the use of aneuploid embryos
created during in vitro fertilization. Technologies have evolved from
fluorescence in situ hybridization to next-generation-sequencing-based aneuploidy
screening and allow for simultaneous testing of multiple genetic abnormalities in
a single biopsy. The field has also shifted away from polar body or blastomere
biopsy and toward trophectoderm biopsy as the new standard. This review describes
the multitude of available platforms and methodologies used in contemporary
preimplantation genetic testing.
PMID- 28498724
TI - Phonological patterns (templates) in 5p deletion syndrome.
AB - Whole word phonological patterns (templates) in utterances produced by children
with 5p deletion syndrome are analysed, addressing four questions: (1) Are
children with 5p deletion syndrome able to generalise over words? (2) How does
the template score of children with 5p deletion syndrome relate to those of
typically developing children and of the target language? (3) How do the template
scores relate to other phonological measures, PCC and consonant variegation? (4)
What can the relationship between template scores and phonological measures tell
us about templates? Children with 5p deletion syndrome are able to generalise
over words, some to a target like extent, others generalise more than expected
for their age. The template scores relate to other phonological measures, with
two exceptions. The exceptions indicate that the template score of a child with
articulatory difficulties may reflect more detailed representations of the words
in memory than she is able to express.
PMID- 28498725
TI - Evaluation of Abbott's BurstDR stimulation device for the treatment of chronic
pain.
AB - INTRODUCTION: Burst stimulation, as described by DeRidder, is a novel waveform
made up of closely spaced, high-frequency electrical impulses delivered in
packets, which are followed by a quiescent period or interburst interval.
Electrically generated burst waveforms were initially designed to treat neural
pathology in the auditory cortex and were later applied to the spinal cord
through spinal cord stimulation (SCS) devices to treat chronic pain states. When
Burst stimulation is applied to the spinal cord, the impulses travel to the
thalamus and then diverge, targeting both the somatosensory cortex and the limbic
system where they treat both the sensory, affective and attentional components of
neuropathic pain. Areas covered: Literature examining clinical and basic research
findings with the application of Burst stimulation to pathologically active
central neural tissue was found using bibliographic databases including PubMed,
Medline, Cochrane, Embase and Google Scholar. Expert commentary: Burst
stimulation offers a salvage strategy for failed tonic spinal cord stimulation
(tSCS), thus improving both quality of life and cost-effectiveness of SCS by
reducing explant rates. The goal of this therapy is to use more than one waveform
in the same device so that lost efficacy from tSCS can be salvaged.
PMID- 28498726
TI - An Analysis of First-Grade Writing Profiles and Their Relationship to
Compositional Quality.
AB - To help all students meet the writing expectations of the Common Core State
Standards, researchers need a deeper understanding of the characteristics of
struggling writers. The purpose of this study was to explore the writing profiles
of students including those who have or are at risk for writing disabilities.
First-grade students ( N = 391) were assessed at the end of the school year using
three writing assessments (spelling, sentence writing fluency, writing
achievement). The researchers used latent profile analysis to identify students
as fitting into one of five profiles (At Risk, Low Fluency, Low Writing, Average,
and Above Average). Students also wrote narrative and descriptive texts that were
scored multiple ways. The researchers used confirmatory factor analysis to
identify four common factors: quality/length, spelling, mechanics, and syntax.
Students in the At Risk profile wrote narratives and descriptions that scored
lower on all aspects of writing when compared to students in the Average and
Above Average profiles. These findings provide further evidence of the distinct
difference among writers as early as first grade, and they offer insight into the
characteristics of at-risk writers. The implications of these findings for
instruction and assessment and directions for future research are described.
PMID- 28498727
TI - Good Prognosis Went Badly: Fulminant Evolution of a 29-Year-Old Patient with
Verrucous Carcinoma of the Cervix.
AB - Verrucous carcinoma (VC) is a very rare variant of squamous cell carcinoma of the
cervix, difficult to point out in histology because of its benign appearance. We
present the case of a 29-year-old woman with a locally advanced cervical VC who
underwent radiotherapy followed by radical hysterectomy. After local relapse and
despite pelvic exenteration, her condition deteriorated. Treatment of choice in
VC is surgery, because of the risk of anaplastic transformation under
irradiation, raising the chances of distant spread and converting this rather
benign-like type of cancer to an aggressive cancer.
PMID- 28498728
TI - A family affair: A Ral-exocyst-centered network links Ras, Rac, Rho signaling to
control cell migration.
AB - Cell migration is central to many developmental, physiologic and pathological
processes, including cancer progression. The Ral GTPases (RalA and RalB) which
act down-stream the Ras oncogenes, are key players in the coordination between
membrane trafficking and actin polymerization. A major direct effector of Ral,
the exocyst complex, works in polarized exocytosis and is at the center of
multiple protein-protein interactions that support cell migration by promoting
protrusion formation, front-rear polarization, and extra-cellular matrix
degradation. In this review we describe the recent advancements in deciphering
the molecular mechanisms underlying this role of Ral via exocyst on cell
migration. Among others, we will discuss the recently identified cross-talk
between Ral and Rac1 pathways: exocyst binds to a negative regulator (the RacGAP
SH3BP1) and to the major effector (the Wave Regulatory Complex, WRC) of Rac1, the
master regulator of protrusions. Next challenge will be to better characterize
the dynamics in space and in time of these molecular interplays, to better
understand the pleiotropic functions of Ral in both normal and cancer cells.
PMID- 28498729
TI - The distinct function of Tep2 and Tep6 in the immune defense of Drosophila
melanogaster against the pathogen Photorhabdus.
AB - Previous and recent investigations on the innate immune response of Drosophila
have identified certain mechanisms that promote pathogen elimination. However,
the function of Thioester-containing proteins (TEPs) in the fly still remains
elusive. Recently we have shown the contribution of TEP4 in the antibacterial
immune defense of Drosophila against non-pathogenic E. coli, and the pathogens
Photorhabdus luminescens and P. asymbiotica. Here we studied the function of Tep
genes in both humoral and cellular immunity upon E. coli and Photorhabdus
infection. We found that while Tep2 is induced after Photorhabdus and E. coli
infection; Tep6 is induced by P. asymbiotica only. Moreover, functional ablation
of hemocytes results in significantly low transcript levels of Tep2 and Tep6 in
response to Photorhabdus. We show that Tep2 and Tep6 loss-of-function mutants
have prolonged survival against P. asymbiotica, Tep6 mutants survive better the
infection of P. luminescens, and both tep mutants are resistant to E. coli and
Photorhabdus. We also find a distinct pattern of immune signaling pathway
induction in E. coli or Photorhabdus infected Tep2 and Tep6 mutants. We further
show that Tep2 and Tep6 participate in the activation of hemocytes in Drosophila
responding to Photorhabdus. Finally, inactivation of Tep2 or Tep6 affects
phagocytosis and melanization in flies infected with Photorhabdus. Our results
indicate that distinct Tep genes might be involved in different yet crucial
functions in the Drosophila antibacterial immune response.
PMID- 28498730
TI - Exploring the Association of Maternal Adverse Childhood Experiences with Maternal
Health and Child Behavior Following Intimate Partner Violence.
AB - BACKGROUND: Adverse childhood experiences (ACEs) have been empirically linked to
a host of negative health outcomes, both physical and psychosocial. Exposures to
ACEs make individuals more susceptible to conditions such as cardiovascular
disease, diabetes, cancers, and depression. Many of these conditions do not
appear until sometime in adolescence or adulthood and have been linked to
premature death. OBJECTIVE: This study explores the association between the
number and type of exposure to ACEs in women (mothers) who experienced intimate
partner violence and health outcomes. Specifically, it explores the association
between maternal ACEs and maternal perceived health and maternal mental and
behavioral health. This study also explores the association between ACEs and
child behavior. METHODS: This analysis is part of a 7-year prospective study. A
cohort of 300 mother-child pairs was assessed at baseline and every 4 months
after reaching out for shelter or justice services for the very first time after
being in an abusive intimate relationship. RESULTS: Data document individual
mothers' ACE scores and show a trend at 12 months, 24 months, and is most
significant at 36 months. Additionally, at 36 months, higher ACE scores were
significantly associated with all child behavioral subscales (anxiety,
depression, aggressive behavior, attention problems, internalizing,
externalizing). CONCLUSION: The women in this study reported ACE scores
consistently higher than national rates. Our data highlight the added benefit of
using ACE criteria as a global prevention strategy to identify those most at risk
for delayed mental and behavioral health issues and to intervene with supportive
strategies and guided referrals as indicated.
PMID- 28498732
TI - Early Writing Intervention: A Best Evidence Synthesis.
AB - The purpose of this best evidence synthesis was to identify promising
interventions that align with a theoretical model of early writing development,
targeting three components of early writing: transcription, text generation, and
self-regulation. We determined the extent to which these interventions are
effective for children who struggle with early writing skills, by calculating
effect sizes for group and single-subject designs, and we examined the overall
quality of the research. Twenty-five studies met inclusion criteria. Among group
design studies, mean effects (Hedge's g) ranged from 0.19 to 1.17 for measures of
writing quantity and from 0.17 to 0.85 for measures of writing quality.
Percentage of all nonoverlapping data for single-subject designs ranged from 83%
to 100% for measures of writing quantity. Interventions with the strongest
evidence of effects and highest methodological quality are described in detail.
Recommendations for research and practice are provided.
PMID- 28498731
TI - Tissue transglutaminase expression is necessary for adhesion, metastatic
potential and cancer stemness of renal cell carcinoma.
AB - Tissue transglutaminase (TG2) is the ubiquitously expressed member of
transglutaminase family and shown to play a critical role in the development and
progression of drug resistance malignancies. We have previously showed the
association of TG2 upregulation with progression and metastasis of renal cell
carcinoma (RCC) and low disease-free survival. In the present study we further
investigate the role of TG2 in cell adhesion, migration and invasion of RCC by
silencing TG2 expression in Caki-2 and A-498 primary site and Caki-1 and ACHN
metastatic site RCC cell lines. Downregulation of TG2 expression led up to a 60%
decrease in actin stress fiber formation and adhesion to beta 1 integrin (ITGB1)
substrates fibronectin, collagen type I and laminin in both primary and
metastatic site RCC cell lines. In addition, treatment with siRNAs against TG2
impaired the migration capacity and cellular invasiveness of ITGB1 substrates in
all 4 RCC cell lines. Lastly, the knockdown of TG2 in metastatic Caki-1 cells
diminished the expression of CD44, CD73-and CD105 cancer stem cell-like markers.
We conclude, for the first time, that TG2 expression is critical for cancer cell
adhesion, migration, invasiveness and cancer cell-stemness during RCC progression
and dissemination. Therefore, combined targeting of TG2 with drugs widely used in
the treatment of RCC may be a promising therapeutic strategy for RCC.
PMID- 28498734
TI - NeurHistAlert 23.
PMID- 28498733
TI - Immunotherapy is different: Implications for vaccine clinical trial design.
AB - Cancer Immunotherapetics differ fundamentally from most cancer therapies in that
they involve manipulation of the immune system to induce an anti-tumor response.
This fundamental difference results in differences in the pre-clinical and
clinical development of immunotherapeutics. Even the regulatory culture of
developing one drug at a time and demonstrating that it, when added to standard
therapy, prolongs patient survival, is often not suitable for the development of
effective immunotherapy regimens. In this commentary, we explore some of these
differences and describe novel clinical trial designs which may be useful in
immunotherapeutics regimen development.
PMID- 28498735
TI - Critical Issues in the Understanding of Young Elementary School Students at Risk
for Problems in Written Expression: Introduction to the Special Series.
AB - In this introduction to the special series "Critical Issues in the Understanding
of Young Elementary School Students at Risk for Problems in Written Expression,"
we consider some of the contextual factors that have changed since a similar
special issue was published in the Journal of Learning Disabilities in 2002. We
also explore how the five articles included in this special series address the
following important themes: early writing development, identification of students
with writing difficulties, and effective interventions for struggling writers. In
conclusion, we envision future directions to advance the field.
PMID- 28498736
TI - ESVM Graz 2017 - Abstracts.
PMID- 28498737
TI - Improved postpartum care after a participatory facilitation intervention in Dar
es Salaam, Tanzania: a mixed method evaluation.
AB - BACKGROUND: In order to improve the health and survival of mothers/newborns, the
quality and attendance rates of postpartum care (PPC) must be increased,
particularly in low-resource settings. OBJECTIVE: To describe outcomes of a
collegial facilitation intervention to improve PPC in government-owned health
institutions in a low-resource suburb in Dar es Salaam, Tanzania. METHODS: A
before-and-after evaluation of an intervention and comparison group was conducted
using mixed methods (focus group discussions, questionnaires, observations,
interviews, and field-notes) at health institutions. Maternal and child health
aiders, enrolled nurse midwives, registered nurse midwives, and medical and
clinical officers participated. A collegial facilitation intervention was
conducted and healthcare providers were organized in teams to improve PPC at
their workplaces. Facilitators defined areas of improvement with colleagues and
met regularly with a supervisor for support. RESULTS: The number of mothers
visiting the institution for PPC increased in the intervention group. Some care
actions were noted in more than 80% of the observations and mothers reported high
satisfaction with care. In the comparison group, PPC continued to be next to non
existent. The healthcare providers' knowledge increased in both groups but was
higher in the intervention group. The t-test showed a significant difference in
knowledge between the intervention and comparison groups and between before and
after the intervention in both groups. The difference of differences for
knowledge was 1.3. The providers perceived the intervention outcomes to include
growing professional confidence/knowledge, improved PPC quality, and mothers'
positive response. The quality grading was based on the national guidelines and
involved nine experts and showed that none of the providers reached the level of
good quality of care. CONCLUSIONS: The participatory facilitation intervention
contributed to improved quality of PPC, healthcare providers' knowledge and
professional confidence, awareness of PPC among mothers, and increased PPC
attendance.
PMID- 28498738
TI - Biogas production from anaerobic digestion of food waste and relevant air quality
implications.
AB - : Biopower can diversify energy supply and improve energy resiliency. Increases
in biopower production from sustainable biomass can provide many economic and
environmental benefits. For example, increasing biogas production through
anaerobic digestion of food waste would increase the use of renewable fuels
throughout California and add to its renewables portfolio. Although a biopower
project will produce renewable energy, the process of producing bioenergy should
harmonize with the goal of protecting public health. Meeting air emission
requirements is paramount to the successful implementation of any biopower
project. A case study was conducted by collecting field data from a wastewater
treatment plant that employs anaerobic codigestion of fats, oils, and grease
(FOG), food waste, and wastewater sludge, and also uses an internal combustion
(IC) engine to generate biopower using the biogas. This research project
generated scientific information on (a) quality and quantity of biogas from
anaerobic codigestion of food waste and municipal wastewater sludge, (b) levels
of contaminants in raw biogas that may affect beneficial uses of the biogas, (c)
removal of the contaminants by the biogas conditioning systems, (d) emissions of
NOx, SO2, CO, CO2, and methane, and (e) types and levels of air toxics present in
the exhausts of the IC engine fueled by the biogas. The information is valuable
to those who consider similar operations (i.e., co-digestion of food waste with
municipal wastewater sludge and power generation using the produced biogas) and
to support rulemaking decisions with regards to air quality issues for such
applications. IMPLICATIONS: Full-scale operation of anaerobic codigestion of food
waste with municipal sludge is viable, but it is still new. There is a lack of
readily available scientific information on the quality of raw biogas, as well as
on potential emissions from power generation using this biogas. This research
developed scientific information with regard to quality and quantity of biogas
from anaerobic co-digestion of food waste and municipal wastewater sludge, as
well as impacts on air quality from biopower generation using this biogas. The
need and performance of conditioning/pretreatment systems for biopower generation
were also assessed.
PMID- 28498741
TI - Growing Momentum for Sugar-Sweetened Beverage Campaigns and Policies: Costs and
Considerations.
PMID- 28498739
TI - Feasibility of a cardiovascular cohort in a Sub-Saharan Africa community:
preliminary report of the pilot project TAHES (Tanve Health Study) in Benin.
AB - BACKGROUND: Faced with the growing burden of cardiovascular disease (CVD)
including atherosclerotic in Sub-Saharan Africa (SSA), the development of
appropriate prediction tools, based on large cohorts, appears useful for
prevention. OBJECTIVE: The objective of the pilot project TAHES (Tanve Health
Study) was to explore the feasibility of a large cohort study focused on CVD and
risk factors in Benin. METHODS: We implemented a prospective cohort over 2 years.
The sample consisted of all people aged 25 years or older who had lived for at
least the previous 6 months in the villages of Tanve or Dekanme. At baseline in
February 2015, behaviours and medical histories were recorded using a
standardized questionnaire adapted from the WHO Steps instrument; screening
questionnaires for angina, claudication, congestive heart failure, and stroke
were applied; anthropometric measures and fasting capillary blood glucose were
taken. All participants were included in the follow-up phase. Surveillance of
target CVD and deaths was implemented through a medical and a community network.
RESULTS: A total of 1,195 participants were enrolled at baseline; women
represented 65.5% and the median age was 39 years. The high participation rate
(91.4%), the quality of baseline data, and the functionality of the events
surveillance network over 8 months indicated good perspective for the feasibility
of a large cohort. We recorded a 3.8% prevalence of daily smoking, 3.6% of
harmful use of alcohol, 10.7% of obesity, 25.5% of high blood pressure, and 3.5%
of diabetes. Prevalence of angina pectoris (2.7%), intermittent claudication
(2.0%), congestive heart failure (0.9%), and stroke survival with motor
impairment (30/00) were also recorded. Ten deaths occurred during the first 8
months, all within households; a cardiovascular cause was suspected in four
cases. CONCLUSION: These preliminary results support the feasibility of
establishing a cohort in Benin. It would require technical and resource support.
PMID- 28498742
TI - Contraindications and Alternatives to Nuanced Corporate Responsibility.
PMID- 28498744
TI - Isolationist Policies Threaten Public Health.
PMID- 28498740
TI - Powassan Virus: An Emerging Arbovirus of Public Health Concern in North America.
AB - Powassan virus (POWV, Flaviviridae) is the only North American member of the tick
borne encephalitis serogroup of flaviviruses. It is transmitted to small- and
medium-sized mammals by Ixodes scapularis, Ixodes cookei, and several other
Ixodes tick species. Humans become infected with POWV during spillover
transmission from the natural transmission cycles. In humans, POWV is the
causative agent of a severe neuroinvasive illness with 50% of survivors
displaying long-term neurological sequelae. POWV was recognized as a human
pathogen in 1958 when a young boy died of severe encephalitis in Powassan,
Ontario, and POWV was isolated from the brain autopsy of this case. Two distinct
genetic lineages of POWV are now recognized: POWV (lineage I) and deer tick virus
(lineage II). Since the index case in 1958, over 100 human cases of POWV have
been reported, with an apparent rise in disease incidence in the past 16 years.
This recent increase in cases may represent a true emergence of POWV in regions
where the tick vector species are prevalent, or it could represent an increase in
POWV surveillance and diagnosis. In the past 5 years, both basic and applied
research for POWV disease has intensified, including phylogenetic studies, field
surveillance, case studies, and animal model development. This review provides an
overview of POWV, including the epidemiology, transmission, clinical disease, and
diagnosis of POWV infection. Recent research developments and future priorities
with regard to the disease are emphasized.
PMID- 28498743
TI - Addressing Zika in the United States: Polarization, Fragmentation, and Public
Health.
PMID- 28498746
TI - The Case for Politics and Public Health: 2017.
PMID- 28498745
TI - Scientific Document Review at the Centers for Disease Control and Prevention: The
CLEAR Approach.
PMID- 28498747
TI - Barriers to Engaging Transgender Women in HIV Observational Research.
PMID- 28498748
TI - Tempels et al. Respond.
PMID- 28498749
TI - Air Mattresses Are Not Appropriate Sleep Spaces for Infants.
PMID- 28498750
TI - Changing Demographics of Marijuana Initiation: Bad News or Good?
PMID- 28498751
TI - Surveillance as Our Sextant.
PMID- 28498753
TI - Evolution of Public Health Surveillance: Status and Recommendations.
PMID- 28498752
TI - Improving Public Health Surveillance About Asian Americans, Native Hawaiians, and
Pacific Islanders.
PMID- 28498754
TI - More Research Is Needed to Understand the Trans Community.
PMID- 28498755
TI - The Value of State-Based Surveillance and Surveys in the United States.
PMID- 28498756
TI - A Public Health of Consequence: Review of the June 2017 Issue of AJPH.
PMID- 28498757
TI - Public Health Surveillance for Communicable Diseases: From Rigid and Static to
Flexible and Innovative.
PMID- 28498759
TI - Social Determinants of Health: Building Wide Coalitions Around Well-Honed
Messages.
PMID- 28498761
TI - Zika's Long Haul: Tackling the Causes of Human Vulnerability to Mosquito-Borne
Viruses.
PMID- 28498762
TI - VanderWeele and Koenig Respond.
PMID- 28498763
TI - Religion and Public Health Curriculum.
PMID- 28498764
TI - VanderWeele and Koenig Respond.
PMID- 28498765
TI - Courses in Religion and Public Health.
PMID- 28498767
TI - AJPH Global News.
PMID- 28498766
TI - Advancing the Field of Public Health Surveillance and Survey Methods.
PMID- 28498768
TI - I Have Randomized by Clinic; Now What? Four Decades After Cornfield.
PMID- 28498769
TI - Ying et al. Respond.
PMID- 28498772
TI - Toward a Comprehensive Policy to Reduce Disparities in Youth Violence.
PMID- 28498770
TI - Major Gun Death Declines in New York, California, and Texas.
PMID- 28498773
TI - Dissemination and Implementation Research: From a Reporting Framework to
Precision Medicine.
PMID- 28498774
TI - A New Day Dawns for Direct-to-Consumer Marketing.
PMID- 28498776
TI - AAV Capsid Engineering: Zooming in on the Target.
PMID- 28498775
TI - Chalcone-based carbamates for Alzheimer's disease treatment.
AB - AIM: Alzheimer's disease is a still untreatable multifaceted pathology, and drugs
able to stop or reverse its progression are urgently needed. In this picture, the
recent reformulation of the cholinergic hypothesis renewed the interest for
acetylcholinesterase inhibitors. In this paper, a series of naturally inspired
chalcone-based carbamates was designed to target cholinesterase enzymes and
possibly generate fragments endowed with neuroprotective activity in situ.
Results & methodology: All compounds presented in this study showed nanomolar
potency for cholinesterase inhibition. Notably, fragment 11d also displayed an
interesting neuroprotective profile. CONCLUSION: These new derivatives are able
to simultaneously modulate different key targets involved in Alzheimer's disease,
and could be regarded as promising starting points for the development of disease
modifying drug candidates. [Formula: see text].
PMID- 28498777
TI - Authors' Response to Jesse D. Riordan, Hum Gene Ther 2017;28:375-376; DOI:
10.1089/hum.2017.045.
PMID- 28498778
TI - Seasonal ambient particulate matter and population health outcomes among
communities impacted by road dust in British Columbia, Canada.
AB - : In recent years, many air quality monitoring programs have favored measurement
of particles less than 2.5 um (PM2.5) over particles less than 10 um (PM10) in
light of evidence that health impacts are mostly from the fine fraction. However,
the coarse fraction (PM10-2.5) may have independent health impacts that support
continued measurement of PM10 in some areas, such as those affected by road dust.
The objective of this study was to evaluate the associations between different
measures of daily PM exposure and two daily indicators of population health in
seven communities in British Columbia, Canada, where road dust is an ongoing
concern. The measures of exposure were PM10, PM2.5, PM10-2.5, PM2.5 adjusted for
PM10-2.5, and PM10-2.5 adjusted for PM2.5. The indicators of population health
were dispensations of the respiratory reliever medication salbutamol sulfate and
nonaccidental mortality. This study followed a time-series design using Poisson
regression over a 2003-2015 study period, with analyses stratified by three
seasons: residential woodsmoke in winter; road dust in spring; and wildfire smoke
in summer. A random-effects meta-analysis was conducted to establish a pooled
estimate. Overall, an interquartile range increase in daily PM10-2.5 was
associated with a 3.6% [1.6, 5.6] increase in nonaccidental mortality during the
road dust season, which was reduced to 3.1% [0.8, 5.4] after adjustment for
PM2.5. The adjusted coarse fraction had no effect on salbutamol dispensations in
any season. However, an interquartile range increase in PM2.5 was associated with
a 2.7% [2.0, 3.4] increase in dispensations during the wildfire season. These
analyses suggest different impacts of different PM fractions by season, with a
robust association between the coarse fraction and nonaccidental mortality in
communities and periods affected by road dust. We recommend that PM10 monitoring
networks be maintained in these communities to provide feedback for future dust
mitigation programs. IMPLICATIONS: There was a significant association between
daily concentrations of the coarse fraction and nonaccidental mortality during
the road dust season, even after adjustment for the fine fraction. The acute and
chronic health effects associated with exposure to the coarse fraction remain
unclear, which supports the maintenance of PM10 monitoring networks to allow for
further research in communities affected by sources such as road dust.
PMID- 28498779
TI - Evaluation of the Education "Clinical Telemedicine/e-Health" in the Curriculum of
Medical Students at the University of Zurich.
AB - BACKGROUND: Digitalization and patient empowerment result in new requirements and
challenges. In response, the module "Clinical Telemedicine/e-Health" was
implemented by the Faculty of Medicine of Zurich in 2008. The module was
systematically evaluated to determine if the students would benefit from this
course. In 2011, 2015, and 2016 further evaluations were performed. METHOD: In
2008 and 2009, students evaluated 16 statements. We calculated the combined mean
value and medians for both evaluations. In 2011, the same evaluation was
conducted, and the results were compared through U-test. In 2015, students were
asked about the application and benefits of telemedicine; the answers were
analyzed qualitatively and quantitatively. In 2016, the University of Zurich
created an online survey which integrated three of the statements from the
original evaluations. RESULTS: Every mean value of the combined evaluations of
2008/2009, 2011, and 2016 achieved a score of over 4 on a 6-point scale. In 2011,
and also again in 2016, the overall satisfaction and understanding of
telemedicine as a supplement in traditional medical consultations increased as
follows: 4.71 +/- 0.74 versus 4.86 +/- 0.93 versus 5.1 +/- 1.5 and, respectively,
5.02 +/- 0.96 versus 5.25 +/- 0.81 versus 5.7 +/- 0.6. In the 2015 evaluation,
93% of students indicated that they would use telemedicine for chronically ill
and elderly patients. CONCLUSION: The positive assessment of the module indicates
the successful introduction of the topics of telemedicine and e-health to medical
students at the University of Zurich. Throughout the course, the students gained
confidence and basic skills.
PMID- 28498780
TI - AP and Ca2+ alternans: An inseparable couple.
PMID- 28498781
TI - Phase I Study and Biomarker Analysis of Pyrotinib, a Novel Irreversible Pan-ErbB
Receptor Tyrosine Kinase Inhibitor, in Patients With Human Epidermal Growth
Factor Receptor 2-Positive Metastatic Breast Cancer.
AB - Purpose This phase I study assessed the safety, tolerability, pharmacokinetics,
antitumor activity, and predictive biomarkers of pyrotinib, an irreversible pan
ErbB inhibitor, in patients with human epidermal growth factor receptor 2 (HER2)
positive metastatic breast cancer. Patients and Methods Pyrotinib was
administered continuously, orally, once per day to patients who did not have
prior exposure to tyrosine kinase inhibitors of HER2. Planned dose escalation was
80, 160, 240, 320, 400, and 480 mg. For pharmacokinetic analysis, timed blood
samples were collected on day 1 and day 28. Next-generation sequencing was
performed on circulating tumor DNA and genomic DNA from tumor samples. Results
Thirty-eight patients were enrolled. The dose-limiting toxicity was grade 3
diarrhea, which occurred in two patients administered 480 mg of pyrotinib; thus,
the maximum tolerated dose was 400 mg. Common pyrotinib-related adverse events
included diarrhea (44.7% [17 of 38]), nausea (13.2% [five of 38]), oral
ulceration (13.2% [five of 38]), asthenia (10.5% [four of 38]), and leukopenia
(10.5% [four of 38]). The only grade 3 adverse event was diarrhea.
Pharmacokinetic analyses indicated that pyrotinib exposure was dose dependent.
The overall response rate was 50.0% (18 of 36), and the clinical benefit rate
(complete response + partial response + stable disease >= 24 weeks) was 61.1% (22
of 36). The median progression-free survival was 35.4 weeks (95% CI, 23.3 to 40.0
weeks). The overall response rate was 83.3% (10 of 12) in trastuzumab-naive
patients and 33.3% (eight of 24) in trastuzumab-pretreated patients. Preliminary
results suggest that PIK3CA and TP53 mutations in circulating tumor DNA ( P =
.013) rather than in archival tumor tissues ( P = .474) may predict the efficacy
of pyrotinib. Conclusion Continuous once-per-day pyrotinib was well tolerated and
demonstrated promising antitumor activity in HER2-positive patients with
metastatic breast cancer. The maximum tolerated dose was established as 400 mg.
Diarrhea was the dose-limiting toxicity. The promising antitumor activity and
acceptable tolerability of pyrotinib warrant its further evaluation in a phase II
study.
PMID- 28498783
TI - Ultrasound Molecular Imaging: A Good Start.
PMID- 28498782
TI - Clonal History and Genetic Predictors of Transformation Into Small-Cell
Carcinomas From Lung Adenocarcinomas.
AB - Purpose Histologic transformation of EGFR mutant lung adenocarcinoma (LADC) into
small-cell lung cancer (SCLC) has been described as one of the major resistant
mechanisms for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
(TKIs). However, the molecular pathogenesis is still unclear. Methods We
investigated 21 patients with advanced EGFR-mutant LADCs that were transformed
into EGFR TKI-resistant SCLCs. Among them, whole genome sequencing was applied
for nine tumors acquired at various time points from four patients to reconstruct
their clonal evolutionary history and to detect genetic predictors for small-cell
transformation. The findings were validated by immunohistochemistry in 210 lung
cancer tissues. Results We identified that EGFR TKI-resistant LADCs and SCLCs
share a common clonal origin and undergo branched evolutionary trajectories. The
clonal divergence of SCLC ancestors from the LADC cells occurred before the first
EGFR TKI treatments, and the complete inactivation of both RB1 and TP53 were
observed from the early LADC stages in sequenced tumors. We extended the findings
by immunohistochemistry in the early-stage LADC tissues of 75 patients treated
with EGFR TKIs; inactivation of both Rb and p53 was strikingly more frequent in
the small-cell-transformed group than in the nontransformed group (82% v 3%; odds
ratio, 131; 95% CI, 19.9 to 859). Among patients registered in a predefined
cohort (n = 65), an EGFR mutant LADC that harbored completely inactivated Rb and
p53 had a 43* greater risk of small-cell transformation (relative risk, 42.8; 95%
CI, 5.88 to 311). Branch-specific mutational signature analysis revealed that
apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC)-induced
hypermutation was frequent in the branches toward small-cell transformation.
Conclusion EGFR TKI-resistant SCLCs are branched out early from the LADC clones
that harbor completely inactivated RB1 and TP53. The evaluation of RB1 and TP53
status in EGFR TKI-treated LADCs is informative in predicting small-cell
transformation.
PMID- 28498785
TI - Laparoscopic Adrenalectomy for Conn's Syndrome is Beneficial to Patients and is
Cost Effective in England.
AB - PURPOSE: Adrenalectomy has the potential to cure or improve the control of
hypertension in patients with primary hyperaldosteronism due to unilateral
adrenal adenoma (Conn's syndrome). This study assesses the patients' perception
of, and costs associated with, laparoscopic adrenalectomy for Conn's syndrome.
MATERIALS AND METHODS: Clinical, radiological, operative, and pathological data
were collected on patients undergoing adrenalectomy for Conn's syndrome over 8
years period in a UK tertiary referral center. RESULTS: Thirty-eight patients
(17M:21F, age 34-79 yrs, median 54 yrs) operated between Jan2005-Sept2012 had
lateralization based on CT scans (n = 30) and/or MRI scans (n = 18) and confirmed
on selective adrenal venous sampling (n = 25). Laparoscopic adrenalectomy was
performed in all patients, with two cases requiring conversion to open operation.
Median operative time was 105 min (range: 27-315). Costs were estimated as L19k
for preoperative investigations, L20k for in-hospital stay, L53k for operating
theatre use and L29k for disposable surgical instruments, with average
L3499/patient (national tariff for adrenalectomy in 2015/2016 L3624). Follow-up
at a mean of 30 months postoperatively using a visual analogue scale and a
standardized questionnaire showed significantly improved quality of life (QoL)
post-operatively. Majority of patients (85%) reported taking none or fewer anti
hypertensive medications (median reduction of 2 antihypertensive drugs). All
patients stated that they would definitely have the operation again in preference
to anti-hypertensive medications and they would recommend the operation to
friends/relatives. CONCLUSIONS: Laparoscopic adrenalectomy for Conn's syndrome
has a positive impact on hypertension control, leads to improved QoL and its
costs are covered in the NHS financial model.
PMID- 28498787
TI - Spatial and temporal variability of atmospheric mercury concentrations emitted
from a coal-fired power plant in Mexico.
AB - : Atmospheric mercury in the environment as a result of the consumption of fossil
fuels, such as coal used in electricity generation, has gained increased
attention worldwide because of its toxicity, atmospheric persistence, and
bioaccumulation. Determining or predicting the concentration of this pollutant in
ambient air is essential for determining sensitive areas requiring health
protection. This study investigated the spatiotemporal variability of gaseous
elemental mercury (GEM) concentrations and its dry deposition surrounding the
Presidente Plutarco Elias Calles (CETEPEC) coal-fired power plant, located on
Mexico's Pacific coast. The CALPUFF dispersion model was applied on the basis of
the daily consumption of coal during 2013 for each generating unit in the power
plant and considering the local scale. The established 300-ng/m3 annual average
risk factor considered by the U.S. Department of Health and Human Services (U.S.
DHHS) and Integrated Risk Information System (IRIS) must not be exceeded to meet
satisfactory air quality levels. An area of 65 * 60 km was evaluated, and the
results show that the risk level for mercury vapor was not exceeded because the
annual average concentration was 2.8 ng/m3. Although the predicted risk level was
not exceeded, continuous monitoring studies of GEM and of particulates in the
atmosphere, soil, and water may be necessary to identify the concentration of
this pollutant, specifically that resulting from coal-fired power plants operated
in environmental areas of interest in Mexico. The dry mercury deposition was low
in the study area; according to the CALPUFF model, the annual average was 1.40E-2
ng/m2/sec. These results represent a starting point for Mexico's government to
implement the Minamata Convention on Mercury, which Mexico signed in 2013.
IMPLICATIONS: The obtained concentrations of mercury from a bigger coal-fired
plant in Mexico, through the application of the CALPUFF dispersion model by the
mercury emissions, are below the level recommended according to the US Department
of Health and Human Services and Integrated Risk Information System. These
results provide evidence of important progress in the planning and installation
to the future of monitoring mercury stations in the area of interest.
PMID- 28498784
TI - Depth of Response in Multiple Myeloma: A Pooled Analysis of Three PETHEMA/GEM
Clinical Trials.
AB - Purpose To perform a critical analysis on the impact of depth of response in
newly diagnosed multiple myeloma (MM). Patients and Methods Data were analyzed
from 609 patients who were enrolled in the GEM (Grupo Espanol de Mieloma) 2000
and GEM2005MENOS65 studies for transplant-eligible MM and the GEM2010MAS65
clinical trial for elderly patients with MM who had minimal residual disease
(MRD) assessments 9 months after study enrollment. Median follow-up of the series
was 71 months. Results Achievement of complete remission (CR) in the absence of
MRD negativity was not associated with prolonged progression-free survival (PFS)
and overall survival (OS) compared with near-CR or partial response (median PFS,
27, 27, and 29 months, respectively; median OS, 59, 64, and 65 months,
respectively). MRD-negative status was strongly associated with prolonged PFS
(median, 63 months; P < .001) and OS (median not reached; P < .001) overall and
in subgroups defined by prior transplantation, disease stage, and cytogenetics,
with prognostic superiority of MRD negativity versus CR particularly evident in
patients with high-risk cytogenetics. Accordingly, Harrell C statistics showed
higher discrimination for both PFS and OS in Cox models that included MRD (as
opposed to CR) for response assessment. Superior MRD-negative rates after
different induction regimens anticipated prolonged PFS. Among 34 MRD-negative
patients with MM and a phenotypic pattern of bone marrow involvement similar to
monoclonal gammopathy of undetermined significance at diagnosis, the probability
of "operational cure" was high; median PFS was 12 years, and the 10-year OS rate
was 94%. Conclusion Our results demonstrate that MRD-negative status surpasses
the prognostic value of CR achievement for PFS and OS across the disease
spectrum, regardless of the type of treatment or patient risk group. MRD
negativity should be considered as one of the most relevant end points for
transplant-eligible and elderly fit patients with MM.
PMID- 28498788
TI - Nutritional status, energy expenditure, and protein oxidative stress after kidney
transplantation.
AB - OBJECTIVES: To evaluate the association between nutritional status, resting
energy expenditure (REE), and protein oxidative stress in patients after kidney
transplantation (KT). METHODOLOGY: The study evaluated 35 patients transplanted
at the time of hospital discharge and 3 months after regarding: body composition,
REE (by indirect calorimetry), and injury factor (IF); serum urea, creatinine,
glucose, albumin, total protein, advanced oxidation protein products (AOPP),
vitamin C. RESULTS: Three months after discharge, there was an improvement in
renal function, nutritional status, and oxidative stress, with a standardization
in the REE/kg. There was an increase in body weight, mainly in fat mass. The
correlations showed that a greater cold ischemia time resulted in a deeper
decline in vitamin C; a longer hospital length stay resulted in a greater
reduction in AOPP; the higher preoperative body weight showed greater increases
in body fat and glucose after transplantation. For decreases in REE and IF, there
were increases in total protein. Finally, at hospital discharge there was a
greater gain in weight, lower albumin, and total protein among individuals who
had rejection episodes. DISCUSSION: The KT improves many of metabolic
abnormalities, with the improvement of nutritional status, oxidative stress, and
normalization of REE.
PMID- 28498789
TI - Corrigendum.
PMID- 28498790
TI - Prognostic Value of Percentage Change in Metabolic Parameters as Measured by Dual
Time Point 18F-FDG PET/CT in Premenopausal Women with Invasive Ductal Breast
Carcinoma.
AB - OBJECTIVES: We retrospectively evaluated the prognostic significance of dual-time
point (DTP) 18F-FDG positron emission tomography/computed tomography (PET/CT)
parameters compared with clinicopathological findings in premenopausal women with
invasive ductal breast carcinoma (IDC). MATERIALS AND METHODS: Sixty-six
premenopausal women (mean age: 42.7 +/- 5.6, range: 29.5-51.8 years) who had
pathologically confirmed IDC were enrolled. The maximum standardized uptake value
(SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were
measured and used to calculate percentage changes over the DTP time interval. We
analyzed the prognostic significance of DTP PET/CT parameters,
clinicopathological factors of pathologic tumor diameter (pTD), axillary lymph
node status (ANS), nuclear grade, histologic grade, and immunohistochemistry
findings using univariate and multivariate analyses. RESULTS: Disease recurrence
was observed in 22 patients. In univariate analysis, SUVmax > 7.39, MTV > 4.28,
TLG > 52.38, %DeltaSUVmax > 20.44, %DeltaTLG > -13.86, pTD > 2.8 cm, positive
ANS, estrogen receptor (ER) negativity, and triple negativity were associated
with worse prognosis than those of opposite groups in recurrence-free survival
(all p < 0.05). %DeltaSUVmax (>20.44, p = 0.0042), TLG (>52.38, p = 0.0002), and
ER negativity (p = 0.0003) were independent prognostic variables after
multivariate analysis. CONCLUSION: Percentage changes in SUVmax using DTP PET/CT
and TLG were significant independent prognostic factors of disease recurrence
along with ER negativity in premenopausal women with IDC.
PMID- 28498791
TI - The influence of successive matches on match-running performance during an under
23 international soccer tournament: The necessity of individual analysis.
AB - This study investigated the effects of successive matches on match-running in
elite under-23 soccer players during an international tournament. Match-running
data was collected using a semi-automated multi-camera tracking system during an
international under-23 tournament from all participating outfield players.
Players who played 100% of all group stage matches were included (3 matches
separated by 72 h, n = 44). Differences in match-running performance between
matches were identified using a generalised linear mixed model. There were no
clear effects for total, walking, jogging, running, high-speed running and
sprinting distance between matches 1 and 3 (effect size (ES); -0.32 to 0.05).
Positional analysis found that sprint distance was largely maintained from
matches 1 to 3 across all positions. Attackers had a moderate decrease in total,
jogging and running distance between matches 1 and 3 (ES; -0.72 to -0.66).
Classifying players as increasers or decreasers in match-running revealed that
match-running changes are susceptible to individual differences. Sprint
performance appears to be maintained over successive matches regardless of
playing position. However, reductions in other match-running categories vary
between positions. Changes in match-running over successive matches affect
individuals differently; thus, players should be monitored on an individual
basis.
PMID- 28498793
TI - Catheter-directed Intraportal Delivery of Endothelial Cell Therapy for Liver
Regeneration: A Feasibility Study in a Large-Animal Model of Cirrhosis.
AB - Purpose To demonstrate the feasibility of imaging-guided catheter-directed
delivery of endothelial cell therapy in a porcine model of cirrhosis for liver
regeneration. Materials and Methods After approval from the institutional animal
care and use committee, autologous liver endothelial cells were grown from core
hepatic specimens from swine. Cirrhosis was induced in swine by means of
transcatheter infusion of ethanol and iodized oil into the hepatic artery. Three
weeks after induction of cirrhosis, the swine were randomly assigned to receive
autologous cell therapy (endothelial cells, n = 4) or control treatment
(phosphate-buffered saline, n = 4) by means of imaging-guided transhepatic
intraportal catheterization. Fluorescence-activated cell sorting analysis was
performed on biopsy samples 1 hour after therapy. Three weeks after intraportal
delivery of endothelial cells, the swine were euthanized and the explanted liver
underwent quantitative pathologic examination. Statistical analysis was performed
with an unpaired t test by using unequal variance. Results Liver endothelial
cells were successfully isolated, cultured, and expanded from eight 20-mm, 18
gauge hepatic core samples to 50 * 106 autologous cells per pig. Intraportal
delivery of endothelial cell therapy or saline was technically successful in all
eight swine, with no complications. Endothelial cells were present in the liver
for a minimum of 1 hour after intraportal infusion. Swine treated with
endothelial cell therapy showed mean levels of surrogate markers of hepatobiliary
injury that were consistent with decreases in hepatic fibrosis and biliary ductal
damage relative to the control animals, although statistical significance was not
met in this pilot study: The mean percentage of positive pixels at Masson
trichrome staining was 7.28% vs 5.57%, respectively (P = .20), the mean
proliferation index with cytokeratin wide-spectrum was 2.55 vs 1.13 (P = .06),
and the mean proliferation index with Ki67 was 7.08 vs 4.96 (P = .14). Conclusion
The results confirm the feasibility of imaging-guided catheter-directed
endothelial cell therapy with an intraportal technique for the treatment of
cirrhosis in a porcine model. A trend toward decreased liver fibrosis with
endothelial cell therapy was observed. Larger animal studies and human studies
are necessary to confirm significance. (c) RSNA, 2017.
PMID- 28498792
TI - Sex Differences in 1-Year Outcomes After Percutaneous Coronary Intervention in
the Veterans Health Administration.
AB - BACKGROUND: Advancements in percutaneous coronary intervention (PCI) for treating
obstructive coronary artery disease have reduced major adverse events, including
mortality. Yet, evidence as to whether women and men experience similar outcomes
is mixed. The objective was to examine sex differences in 1-year major adverse
cardiac outcomes for the national population of patients undergoing PCI at
Veterans Health Administration (VA) cardiac catheterization laboratories.
METHODS: All Veterans undergoing PCI at VA hospitals between October 1, 2007 and
September 30, 2013 (N = 64,757; Women = 1,040) were included. Cox proportional
hazards models compared 1-year postprocedural outcomes [rehospitalization for
myocardial infarction (MI), all-cause mortality, and major adverse cardiovascular
events (MACE)] by sex. RESULTS: Women Veterans undergoing PCI were more likely to
be younger, black, obese, and have chronic depression and less likely to have
common cardiovascular risk factors and to have had prior cardiac events than
Veteran men. One-year rates for women versus men were 2.1% and 2.5% for
rehospitalization (p-value = 0.57); 3.5% and 4.9% for mortality (p-value = 0.14),
and 5.4% and 6.9% for MACE (p-value = 0.18). There were no significant sex
differences in any of the outcomes in Cox proportional hazards models.
CONCLUSIONS: Despite differences in clinical risk factors at the time of PCI,
women and men Veterans treated at VA cardiac catheterization laboratories
experienced comparable 1-year rehospitalization for MI, mortality, and MACE post
PCI. These results demonstrated similar 1-year post-PCI outcomes for men and
women in a national population of patients who have more comorbidities and mental
health issues than the general population.
PMID- 28498794
TI - Diagnosis of Normal-Pressure Hydrocephalus: Use of Traditional Measures in the
Era of Volumetric MR Imaging.
AB - Purpose To assess the diagnostic performance of the callosal angle (CA) and Evans
index (EI) measures and to determine their role versus automated volumetric
methods in clinical radiology. Materials and Methods Magnetic resonance (MR)
examinations performed before surgery (within 1-5 months of the MR examination)
in 36 shunt-responsive patients with normal-pressure hydrocephalus (NPH; mean
age, 75 years; age range, 58-87 years; 26 men, 10 women) and MR examinations of
age- and sex-matched patients with Alzheimer disease (n = 34) and healthy control
volunteers (n = 36) were studied. Three blinded observers independently measured
EI and CA for each patient. Volumetric segmentation of global gray matter, white
matter, ventricles, and hippocampi was performed by using software. These
measures were tested by using multivariable logistic regression models to
determine which combination of metrics is most accurate in diagnosis. Results The
model that used CA and EI demonstrated 89.6%-93.4% accuracy and average area
under the curve of 0.96 in differentiating patients with NPH from patients
without NPH (ie, Alzheimer disease and healthy control). The regression model
that used volumetric predictors of gray matter and white matter was 94.3%
accurate. Conclusion CA and EI may serve as a screening tool to help the
radiologist differentiate patients with NPH from patients without NPH, which
would allow for designation of patients for further volumetric assessment. (c)
RSNA, 2017.
PMID- 28498795
TI - Comparison of fetal weight distribution improved by paternal height by Spanish
standard versus Intergrowth 21st standard.
PMID- 28498796
TI - Interactions between cannabis and schizophrenia in humans and rodents.
AB - In this review, we provide an overview of the relationship between cannabis use
and the development of schizophrenia, using both animal and human studies. We
further discuss the potential neural mechanism that may mediate the relationship
between cannabis use and schizophrenia symptoms. We finally provide clinical
implications and future studies that can further elucidate the relationship
between cannabis and schizophrenia.
PMID- 28498797
TI - NatB-mediated protein N-alpha-terminal acetylation is a potential therapeutic
target in hepatocellular carcinoma.
AB - The identification of new targets for systemic therapy of hepatocellular
carcinoma (HCC) is an urgent medical need. Recently, we showed that hNatB
catalyzes the N-alpha-terminal acetylation of 15% of the human proteome and that
this action is necessary for proper actin cytoskeleton structure and function. In
tumors, cytoskeletal changes influence motility, invasion, survival, cell growth
and tumor progression, making the cytoskeleton a very attractive antitumor
target. Here, we show that hNatB subunits are upregulated in in over 59% HCC
tumors compared to non-tumor tissue and that this upregulation is associated with
microscopic vascular invasion. We found that hNatB silencing blocks proliferation
and tumor formation in HCC cell lines in association with hampered DNA synthesis
and impaired progression through the S and the G2/M phases. Growth inhibition is
mediated by the degradation of two hNatB substrates, tropomyosin and CDK2, which
occurs when these proteins lack N-alpha-terminal acetylation. In addition, hNatB
inhibition disrupts the actin cytoskeleton, focal adhesions and tight/adherens
junctions, abrogating two proliferative signaling pathways, Hippo/YAP and ERK1/2.
Therefore, inhibition of NatB activity represents an interesting new approach to
treating HCC by blocking cell proliferation and disrupting actin cytoskeleton
function.
PMID- 28498798
TI - Differential expression of miR-195-5p in collapse of steroid-induced
osteonecrosis of the femoral head.
AB - BACKGROUND: Femoral head collapse is a key reference point for determining a
treatment regimen of femoral head osteonecrosis. However, there are no effective
preventive measures and the efficacy of hip-preserving surgery is unsatisfactory
due to the unclear mechanism of collapse. This study aimed to identify and
validate miRNAs differentially expressed in collapse and non-collapse areas of
the osteonecrotic femoral head, and to predict the target genes and pathways of
these miRNAs. RESULTS: Nine samples passed the quality control test. A total of
2085 differentially expressed miRNAs were detected, among which 433 miRNAs showed
differential expression in the T1 group compared to the W1 group; 344 miRNAs
showed differential expression in the T2 group compared to the W2 group; 107
miRNAs showed differential expression in the T3 group compared to the W3 group.
After combining data from all three patients, 10 miRNAs showed differential
expression in the collapse area (T1+T2+T3) compared to the non-collapse area
(W1+W2+W3). Compared to the normal area, has-miR-195-5p showed the most
significant downregulation. Expression results from RT-PCR revealed that the
expression of hsa-miR-195-5p in the collapse area (T1+T2+T3) was significantly
lower than that in the non-collapse area (W1+W2+W3) and normal area (Z1+Z2+Z3).
157 genes were perdicted as the target gene of hsa-miR-195-5p. MATERIALS AND
METHODS: Femoral heads of three patients (2 males and 1 female) treated by total
hip arthroplasty surgery for steroid-induced femoral head osteonecrosis were
selected based on inclusion and exclusion criteria. Bone tissue samples were
obtained from the collapse area (T), non-collapse area (W), and normal area (Z)
according to the anatomical structure of osteonecrotic femoral heads. Total RNA
was extracted from the samples and the microarray chip was scanned. miRNAs
showing differential expressions of more than 1.5-fold were selected and was
validated by RT-PCR. TargetScan, mirBase and miRanda bioinformatics software was
used to predict target genes and identify possible pathways involving these
genes. CONCLUSIONS: miR-195-5p showed the most significant difference in the
collapse area of osteonecrotic femoral heads, suggesting that collapse may be
related to the downregulation of miR-195-5p.
PMID- 28498799
TI - Dietary luteolin attenuates chronic liver injury induced by mercuric chloride via
the Nrf2/NF-kappaB/P53 signaling pathway in rats.
AB - Mercury exposure is a common cause of metal poisoning which is biotransformed to
highly toxic metabolites thus eliciting biochemical alterations and oxidative
stress. Luteolin, a phenolic compound found in many natural products, has
multiple biological functions. Our study was aimed to explore the biological
effects of luteolin in a liver injury model induced in rats by mercuric chloride
(HgCl2). Criteria for injury included liver enzyme, glutathione and
malondialdehyde levels, histopathology, TUNEL assay, hepatocyte viability and
reactive oxygen species levels. The results showed that luteolin protected
against HgCl2-induced liver injury. Luteolin increased total nuclear factor
erythroid-2-related factor 2 (Nrf2) levels in the presence of HgCl2. Upregulation
of its downstream factors, heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1,
was also observed. This suggested that protection by luteolin against HgCl2
induced liver injury involved Nrf2 pathway activation. Luteolin also decreased
expression of nuclear factor-kappaB (NF-kappaB) and P53. HgCl2 exposure led to
increased Bcl-associated X protein (Bax), and decreased Bcl-2-related protein
long form of Bcl-x (Bcl-xL) and B-cell leukemia/lymphoma-2 (Bcl-2) expression,
leading to an increased Bax/Bcl-2 ratio. Taken together, our data suggested that
decreasing oxidative stress is a protective mechanism of luteolin against
development of HgCl2-induced liver injury, through the Nrf2/NF-kappaB/P53
signaling pathway in rats.
PMID- 28498800
TI - Locally-applied 5-fluorouracil-loaded slow-release patch prevents pancreatic
cancer growth in an orthotopic mouse model.
AB - To obtain improved efficacy against pancreatic cancer, we investigated the
efficacy and safety of a locally-applied 5-fluorouracil (5-FU)-loaded polymeric
patch on pancreatic tumors in an orthotopic nude-mouse model. The 5-FU-releasing
polymeric patch was produced by 3D printing. After application of the patch, it
released the drug slowly for 4 weeks, and suppressed BxPC-3 pancreas cancer
growth. Luciferase imaging of BxPC3-Luc cells implanted in the pancreas was
performed longitudinally. The drug patch delivered a 30.2 times higher level of 5
FU than an intra-peritoneal (i.p.) bolus injection on day-1. High 5-FU levels
were accumulated within one week by the patch. Four groups were compared for
efficacy of 5-FU. Drug-free patch as a negative control (Group I); 30% 5-FU
loaded patch (4.8 mg) (Group II); 5-FU i.p. once (4.8 mg) (Group III); 5-FU i.p.
once a week (1.2 mg), three times (Group IV). The tumor growth rate was
significantly faster in Group I than Group II, III, IV (p=0.047 at day-8, p=0.022
at day-12, p=0.002 at day-18 and p=0.034 at day-21). All mice in Group III died
of drug toxicity within two weeks after injection. Group II showed more effective
suppression of tumor growth than Group IV (p=0.018 at day-12 and p=0.017 at day
21). Histological analysis showed extensive apoptosis in the TUNEL assay and by
Ki -67 staining. Western blotting confirmed strong expression of cleaved caspase
3 in Group II. No significant changes were found hematologically and
histologically in the liver, kidney and spleen in Groups I, II, IV but were found
in Group III.
PMID- 28498802
TI - Sales for anti-angiogenic drugs.
PMID- 28498803
TI - Differentially expressed proteins in glioblastoma multiforme identified with a
nanobody-based anti-proteome approach and confirmed by OncoFinder as possible
tumor-class predictive biomarker candidates.
AB - Glioblastoma multiforme is the most frequent primary malignancy of the central
nervous system. Despite remarkable progress towards an understanding of tumor
biology, there is no efficient treatment and patient outcome remains poor. Here,
we present a unique anti-proteomic approach for selection of nanobodies specific
for overexpressed glioblastoma proteins. A phage-displayed nanobody library was
enriched in protein extracts from NCH644 and NCH421K glioblastoma cell lines.
Differential ELISA screenings revealed seven nanobodies that target the following
antigens: the ACTB/NUCL complex, VIM, NAP1L1, TUFM, DPYSL2, CRMP1, and ALYREF.
Western blots showed highest protein up-regulation for ALYREF, CRMP1, and VIM.
Moreover, bioinformatic analysis with the OncoFinder software against the
complete "Cancer Genome Atlas" brain tumor gene expression dataset suggests the
involvement of different proteins in the WNT and ATM pathways, and in Aurora B,
Sem3A, and E-cadherin signaling. We demonstrate the potential use of NAP1L1,
NUCL, CRMP1, ACTB, and VIM for differentiation between glioblastoma and lower
grade gliomas, with DPYSL2 as a promising "glioma versus reference" biomarker. A
small scale validation study confirmed significant changes in mRNA expression
levels of VIM, DPYSL2, ACTB and TRIM28. This work helps to fill the information
gap in this field by defining novel differences in biochemical profiles between
gliomas and reference samples. Thus, selected genes can be used to distinguish
glioblastoma from lower grade gliomas, and from reference samples. These findings
should be valuable for glioblastoma patients once they are validated on a larger
sample size.
PMID- 28498804
TI - Increased S100A15 expression and decreased DNA methylation of its gene promoter
are involved in high metastasis potential and poor outcome of lung
adenocarcinoma.
AB - PURPOSE: This study aims to determine the functional role of S100A15 and its
promoter DNA methylation patterns in lung cancer progression. EXPERIMENTAL
DESIGN: We analyzed 178 formalin-fixed paraffin embedded specimens from lung
cancer patients, including 24 early stage and 91 advanced stage adenocarcinoma.
S100A15 protein expression was evaluated by immunohistochemistry stain, and its
DNA methylation levels were measured by pyrosequencing. RESULTS: S100A15 nuclear
staining was increased in lung adenocarcinoma patients with distant metastasis
versus those without distant metastasis. There was reduced one/three-year overall
survival in adenocarcinoma patients receiving first line target therapy and
harboring high nuclear expressions of S100A15. Both DNA methylation levels over
423 and -248 CpG sites of the S100A15 gene promoter were decreased in
adenocarcinoma patients with distant metastasis, and the former was associated
with lower one-year overall survival. The highly invasive CL1-5 cell lines
display decreased DNA methylation over -412/-248/-56 CpG sites of the S100A15
gene promoter and increased S100A15 gene/protein expressions as compared with the
less invasive CL1-0 cell lines. Knockdown of S100A15 in CL1-5 cell line inhibited
cell proliferation, migration, and invasion, while over-expression of S100A15 in
CL1-0 cell line promoted cell proliferation, migration, and invasion. RNA
sequencing analysis revealed potential biological effects of S100A15 over
expression and knock-down with CTNNB1, ZEB1, CDC42, HSP90AA1, BST2, and PCNA
being the pivotal down-stream mediators. CONCLUSIONS: Increased S100A15
expression and decreased DNA methylation of its gene promoter region were
associated with high metastasis potential and poor outcome in lung
adenocarcinoma, probably through triggering CTNNB1 -centered pathways.
PMID- 28498805
TI - FOXM1 predicts overall and disease specific survival in muscle-invasive
urothelial carcinoma and presents a differential expression between bladder
cancer subtypes.
AB - Forkhead box M1 (FOXM1) is a late cell cycle gene that plays a crucial role in
carcinogenesis and chemotherapeutic drug resistance. In this study, the impact of
FOXM1 expression on patient outcome was investigated for the first time in
formalin fixed and paraffin embedded (FFPE) samples of chemotherapy naive muscle
invasive bladder cancer (MIBC) patients. Expression analyses were performed on
the Mannheim cohort (n=84) and validated on the independent Chungbuk cohort
(n=61). In a Cox' proportional hazards model, a distinct FOXM1 expression cut-off
dividing both cohorts in a 'high-risk' and 'low-risk' group has been determined.
Multivariate analyses showed that FOXM1 is an independent risk factor for outcome
prediction superior to the TNM system. The FOXM1 'high-risk' group had a 4- to 7
fold increased risk of death (p<0.03) and presented further an overexpression of
MKI67. Recent studies showed that MIBCs can be subclassified in breast cancer
like subtypes: basal, luminal and p53-like. Here we demonstrated that FOXM1 was
differentially expressed between MIBC subtypes concordant to its subtype specific
expression in breast cancer. Since the proto-oncogene FOXM1 is known to play an
important role in cisplatin resistance and to be a promising drug target, this
study supports FOXM1 as a crucial biomarker in the personalization of MIBC
therapy and urges prospective translational studies.
PMID- 28498806
TI - Epigenetic modifiers upregulate MHC II and impede ovarian cancer tumor growth.
AB - Expression of MHC class II pathway proteins in ovarian cancer correlates with
prolonged survival. Murine and human ovarian cancer cells were treated with
epigenetic modulators - histone deacetylase inhibitors and a DNA
methyltransferase inhibitor. mRNA and protein expression of the MHC II pathway
were evaluated by qPCR and flow cytometry. Treatment with entinostat and
azacytidine of ID8 cells in vitro increased mRNA levels of Cd74, Ciita, and H2
Aa, H2-Eb1. MHC II and CD74 protein expression were increased after treatment
with either agent. A dose dependent response in mRNA and protein expression was
seen with entinostat. Combination treatment showed higher MHC II protein
expression than with single agent treatment. In patient derived xenografts,
CIITA, CD74, and MHC II mRNA transcripts were significantly increased after
combination treatment. Expression of MHC II on ovarian tumors in MISIIR-Tag mice
was increased with both agents relative to control. Combination treatment
significantly reduced ID8 tumor growth in immune-competent mice. Epigenetic
treatment increases expression of MHC II on ovarian cancer cells and impedes
tumor growth. This approach warrants further study in ovarian cancer patients.
PMID- 28498807
TI - Knockdown of PKM2 and GLS1 expression can significantly reverse oxaliplatin
resistance in colorectal cancer cells.
AB - Clinical treatment for colorectal cancer (CRC) thus far encounters a huge
challenge due to oxaliplatin-resistance. As crucial rate-limiting enzymes in
aerobic glycolysis and glutaminolysis, pyruvate kinase M2 type (PKM2) and kidney
type glutaminase (GLS1) are proposed to carry important implications in
colorectal carcinogenesis and drug-resistance. This study aimed to explore the
possible association of oxaliplatin-resistance with aerobic
glycolysis/glutaminolysis indexed by PKM2/GLS1 expression. PKM2 and GLS1
expression was quantified by polymerase chain reaction (PCR) and Western blot
techniques in CRC cell lines. The abilities of cell formation, kinetics,
migration, invasion, survival and apoptosis, as well as permeability glycoprotein
(Pgp) expression were inspected before and after knocking-down PKM2/GLS1
expression. In addition, the influence of knocking-down PKM2/GLS1 expression was
evaluated in vivo. Differentiated PKM2 and GLS1 expression in both THC8307 and
THC8307/Oxa cell lines was identified. In the THC8307 cell line, PKM2 and GLS1
can accelerate malignant behaviors, increase oxaliplatin-resistance, upregulate
Pgp expression, and inhibit cell apoptosis. Contrastingly in the THC8307/Oxa cell
line, knockdown of PKM2/GLS1 expression can restrain malignant behaviors,
reestablish oxaliplatin-sensitivity, downregulate Pgp expression, and induce cell
apoptosis. In xenograft, knockdown of PKM2/GLS1 expression can significantly
inhibit tumor growth, reduce Pgp expression, and increase tumor apoptosis. Taken
together, the present findings enriched our knowledge by demonstrating a
significant association of PKM2 and GLS1 with oxaliplatin-resistance in CRC. We
further propose that knockdown of PKM2/GLS1 expression may constitute a novel
therapeutic strategy toward effective treatment for CRC.
PMID- 28498808
TI - Restoration of p53 using the novel MDM2-p53 antagonist APG115 suppresses
dedifferentiated papillary thyroid cancer cells.
AB - Dedifferentiated papillary thyroid cancer (DePTC) is characterized by aggressive
growth, recurrence, distant metastasis, and resistance to radioactive iodine
(RAI) therapy. DePTC is also accompanied by poor prognosis and high early
mortality. Nevertheless, most DePTC cells show intact p53 downstream
functionality. In cells with wild-type p53, the murine double minute2 (MDM2)
protein interacts with p53 and abrogates its activity. Inhibition of the MDM2-p53
interaction restores p53 activity and leads to cell cycle arrest and apoptosis.
Restoring p53 function by inhibiting its interaction with p53 suppressors such as
MDM2 is thus a promising therapeutic strategy for the treatment of DePTC. The
novel MDM2-p53 interaction antagonist APG115 is an analogue of SAR405838, and is
being tested in a phase I clinical trial. In this study, we evaluated the
efficacy of APG115 as a single-agent to treat DePTC. APG115 diminished the
viability of p53 wild-type DePTC cells and induced cell cycle arrest and
apoptosis. In a human xenograft mouse model, APG115 elicited robust tumor
regression and cell apoptosis. These data demonstrate that further research is
warranted to determine whether APG115 can be used to effectively treat DePTC
patients.
PMID- 28498809
TI - Follistatin-like protein 1 promotes inflammatory reactions in nucleus pulposus
cells by interacting with the MAPK and NFkappaB signaling pathways.
AB - OBJECTIVE: Follistatin-like protein 1 (FSTL1) is a well-known mediator of
inflammation. Intervertebral disc disease is an inflammatory disorder. Here, we
investigated the role of FSTL1 in the intervertebral discs inflammation. METHODS:
Expression of FSTL1 in nucleus pulposus tissues from rats and human was
determined by immunohistochemistry staining and western blot analysis. The
expression levels of tumor necrosis factor-alpha (TNF-alpha), interleukin1-beta
(IL-1beta) and matrix metalloproteinase 13 (MMP-13) in human and rat nucleus
pulposus tissues were measured by immunohistochemistry staining. The mitogen
activated protein kinase (MAPK) and nuclear factor-kappa B (NFkappaB) signaling
pathways were detected by western blotting. RESULTS: FSTL1 serum levels were
significantly increased in lumbar disc herniation patients and had a positive
correlation with Visual Analogue Scores. Additionally, FSTL1 expression was
significantly increased in extrusion group compared with protrusion and control
groups. Furthermore, FSTL1 expression was significantly increased in
intervertebral disc degeneration models of rats. Immunohistochemistry staining
demonstrated that the levels of TNF-alpha, IL-1beta and MMP-13 were increased in
the pathogenesis of intervertebral disc disease. Recombinant human FSTL1
significantly increased the production of proinflammatory cytokines in vitro. In
addition, FSTL1 promoted inflammation by activating c-Jun N-terminal kinase
(JNK), extracellular regulated protein kinases 1/2(ERK1/2) and NFkappaB
signaling. CONCLUSIONS: These data imply that FSTL1 expression was increased in
the pathogenesis of intervertebral disc disease. Importantly, FSTL1 promoted
inflammatory catabolism in the nucleus pulposus by activating JNK, ERK 1/2/MAPK
and NFkappaB signaling.
PMID- 28498811
TI - The generation and functional characterization of induced pluripotent stem cells
from human intervertebral disc nucleus pulposus cells.
AB - Disc degenerative disease (DDD) is believed to originate in the nucleus pulposus
(NP) region therefore, it is important to obtain a greater number of active NP
cells for the study and therapy of DDD. Human induced pluripotent stem cells
(iPSCs) are a powerful tool for modeling the development of DDD in humans, and
have the potential to be applied in regenerative medicine. NP cells were isolated
from DDD patients following our improved method, and then the primary NP cells
were reprogramed into iPSCs with Sendai virus vectors encoding 4 factors.
Successful reprogramming of iPSCs was verified by the expression of surface
markers and presence of teratoma. Differentiation of iPSCs into NP-like cells was
performed in a culture plate or in hydrogel, whereby skin fibroblast derived
iPSCs were used as a control. Results demonstrated that iPSCs derived from NP
cells displayed a normal karyotype, expressed pluripotency markers, and formed
teratoma in nude mice. NP induction of iPSCs resulted in the expression of NP
cell specific matrix proteins and related genes. Non-induced NP derived-iPSCs
also showed some NP-like phenotype. Furthermore, NP-derived iPSCs differentiate
much better in hydrogel than that in a culture plate. This is a novel method for
the generation of iPSCs from NP cells of DDD patients, and we have successfully
differentiated these iPSCs into NP-like cells in hydrogel. This method provides a
novel treatment of DDD by using patient-specific NP cells in a relatively simple
and straightforward manner.
PMID- 28498810
TI - The prognostic value of GLUT1 in cancers: a systematic review and meta-analysis.
AB - Increased glycolysis is one of the hallmarks of cancer. The abnormal expression
of glucose transporter 1 (GLUT1) was reported to be associated with resistance to
current therapy and poor prognosis. Numerous studies have investigated the
correlation between GLUT1 expression and prognosis in cancers, but the
conclusions are still controversial. Here, we conducted a meta-analysis to
explore the association between GLUT1 and survival in human cancers. PubMed,
Springer, Medline, and Cochrane Library were searched carefully to identify
eligible studies evaluating prognostic value of GLUT1 in cancers. Twenty-seven
studies with 4079 patients were included in the present study. Our pooled results
identified that increased expression of GLUT1 was associated with unfavorable
overall survival (HR = 1.780, 95% CI = 1.574-.013, p < 0.001)) and poorer disease
free survival (HR = 1.95, 95% CI = 1.229-3.095, p = 0.003). Furthermore,
overexpression of GLUT1 linked with poor differentiated tumors (RR = 1.380, 95%
CI = 1.086-1.755, p = 0.009; I2 = 72.0%, p < 0.001), positive lymph node
metastasis (RR = 1.395, 95% CI = 1.082-1.799, p = 0.010; I2 = 70.8%, p = 0.002)
and larger tumor size (RR = 1.405, 95% CI = 1.231-1.603, p < 0.001; I2 = 37.3%, p
= 0.093). This systematic review and meta-analysis indicated that the GLUT1 may
serve as an ideal prognostic biomarker in various cancers.
PMID- 28498812
TI - Structure based discovery of clomifene as a potent inhibitor of cancer-associated
mutant IDH1.
AB - Isocitrate dehydrogenase (IDH) plays an indispensable role in the tricarboxylic
acid cycle, and IDH mutations are present in nearly 75% of glioma and 20% of
acute myeloid leukemia. One IDH1R132H inhibitor (clomifene citrate) was found by
virtual screening method, which can selectively suppress mutant enzyme activities
in vitro and in vivo with a dose-dependent manner. The molecular docking
indicated that clomifene occupied the allosteric site of the mutant IDH1.
Enzymatic kinetics also demonstrated that clomifene inhibited mutant enzyme in a
non-competitive manner. Moreover, knockdown of mutant IDH1 in HT1080 cells
decreased the sensitivity to clomifene. In vivo studies indicated that clomifene
significantly suppressed the tumor growth of HT1080-bearing CB-17/Icr-scid mice
with oral administration of 100 mg/kg and 50 mg/kg per day. In short, our
findings highlight clomifene may have clinical potential in tumor therapies as a
safe and effective inhibitor of mutant IDH1.
PMID- 28498813
TI - Microwave ablation combined with attenuated Salmonella typhimurium for treating
hepatocellular carcinoma in a rat model.
AB - We aim to investigate the safety and efficacy of microwave ablation (MWA)
combined with attenuated Salmonella typhimurium strain VNP20009 in treating
hepatocellular carcinoma. Portions of tumor tissues were orthotopically implanted
in the livers of 40 male rats weighed 150~200 g to establish tumor models. Three
weeks later, the rats were randomly divided into four groups: (A) MWA plus
VNP20009 group; (B) MWA group; (C) VNP20009 group; and (D) control group.
Incomplete MWA was performed (20~30 W, 1~2 min) after the hepatic carcinoma was
properly exposed. VNP20009 (about 1*107 cfu) was directly injected into the tumor
immediately. MRI scans were performed to assess the tumor responses 7 and 14 days
later, respectively. Micro CT was used to observe the lung metastases. After the
animals were sacrificed or died, the tumors were cut off for the purpose of
pathological and immunohistochemical analyses. The results showed that the mean
tumor volumes of MWA plus VNP20009 group on the 7th and 14th day post treatment
were obviously smaller than those of other groups (P < 0.05). Lung metastases
rates were 20%, 60%, 30% and 100% in MWA plus VNP20009 group, MWA group, VNP20009
group and control group, respectively. The median survival of the rats in MWA
plus VNP20009 group was distinctly longer than those in other groups (P < 0.05).
In summary, MWA combined with VNP20009 produced better effects than MWA or
VNP20009 alone in treating hepatic carcinoma. This strategy might have potential
ability to decrease lung metastases and prolong the overall survival.
PMID- 28498814
TI - Methyl jasmonate leads to necrosis and apoptosis in hepatocellular carcinoma
cells via inhibition of glycolysis and represses tumor growth in mice.
AB - Methyl jasmonate has recently been found to have anti-cancer activity. Methyl
jasmonate detached hexokinase 2 from a voltage dependent anion channel causing a
reduction in mitochondrial transmembrane potential that led to the release of
cytochrome C and apoptosis inducing factor resulting in intrinsic apoptosis.
Blocked adenosine triphosphate synthesis caused by mitochondrial injury hampered
oxidative phosphorylation and led to cell necrosis. The results were applied to
the in vivo treatment of nude mice with a satisfactory effect. Collectively, our
results suggest that methyl jasmonate may be an adjuvant therapy for liver tumors
due to its mechanism in cancer cells compared to that in normal cells: The major
function is to inhibit glycolysis instead of changing aerobic metabolism.
PMID- 28498815
TI - The optimization of cell therapy by combinational application with apicidin
treated mesenchymal stem cells after myocardial infarction.
AB - Although mesenchymal stem cells (MSC) have been shown to be safe in preclinical
studies of cardiovascular disease, multiple meta-analyses have debated whether
functional improvement is significant or not. The cardiac differentiation from
MSC is achievable using cardiogenic factors, however, the high cost and long
culture period may limit the applications. Here, we developed a novel method to
optimize the therapeutic outcome for myocardial infarction (MI). Treatment of MSC
with apicidin, a histone deacetylase inhibitor, dramatically increased the
expressions of cardiac markers such as GATA4, Nkx2.5, and cardiac troponin I
(cTnI). In AC/MSC, stemness-related genes and yes-associated protein (YAP), a
potent oncogene that drives cell proliferation, were significantly suppressed.
Furthermore apicidin treatment or YAP knockdown downregulated miR-130a expression
followed by induction of cardiac markers in MSC. In the comparison study, we
found that both cardiac gene induction and angiogenesis were most prominent in
the mixture of non-treated MSC and AC/MSC (Mix). Using mouse MI model, we show
that application of Mix was strongly associated with cardiac differentiation of
injected MSC and improved cardiac performance. Our results suggest that
suppression of YAP/miR-130a shifts MSC cell fate toward cardiac lineage and
identify apicidin as a potential pharmacological target for therapeutic
development.
PMID- 28498820
TI - Lysosomal regulation of cholesterol homeostasis in tuberous sclerosis complex is
mediated via NPC1 and LDL-R.
AB - Tuberous sclerosis complex (TSC) is a multisystem disease associated with
hyperactive mTORC1. The impact of TSC1/2 deficiency on lysosome-mediated
processes is not fully understood. We report here that inhibition of lysosomal
function using chloroquine (CQ) upregulates cholesterol homeostasis genes in TSC2
deficient cells. This TSC2-dependent transcriptional signature is associated with
increased accumulation and intracellular levels of both total cholesterol and
cholesterol esters. Unexpectedly, engaging this CQ-induced cholesterol uptake
pathway together with inhibition of de novo cholesterol synthesis allows survival
of TSC2-deficient, but not TSC2-expressing cells. The underlying mechanism of
TSC2-deficient cell survival is dependent on exogenous cholesterol uptake via LDL
R, and endosomal trafficking mediated by Vps34. Simultaneous inhibition of
lysosomal and endosomal trafficking inhibits uptake of esterified cholesterol and
cell growth in TSC2-deficient, but not TSC2-expressing cells, highlighting the
TSC-dependent lysosome-mediated regulation of cholesterol homeostasis and
pointing toward the translational potential of these pathways for the therapy of
TSC.
PMID- 28498823
TI - Enhancing the thermal dissipation of a light-converting composite for quantum dot
based white light-emitting diodes through electrospinning nanofibers.
AB - Quantum dots (QDs) have been developed as one of the most promising light
converting materials for white light-emitting diodes (LEDs). In current QD-based
LED packaging structures, composites of QDs and polymers are used as light
converting layers. However, the ultralow thermal conductivity of such composites
seriously hinders the dissipation of QD-generating heat. In this paper, we
demonstrate a method to enhance the thermal dissipation of QD-polymer composites
through electrospinning polymer nanofibers. QD-polymer films embedded by
electrospun nanofibers were prepared. Benefitting from aligned polymer chains in
the electrospun nanofibers, the through-panel and in-panel thermal conductivities
of the proposed QD-polymer film increased by 39.9% and 423.1%, respectively,
compared to traditional QD-polymer film. The proposed and traditional QD-polymer
films were both packaged on chip on board (CoB) LEDs for experimental comparison.
Compared to traditional QD-polymer film, the luminous flux and luminous
efficiency of the LEDs were increased by up to 51.8% and 42.9% by the proposed QD
polymer film under a current of 800 mA, respectively. With an increase in the
driving current from 20-800 mA, the correlated color temperature (CCT) variation
decreased by 72.7%. The maximum temperatures in the QD-polymer films were reduced
from 419 K-411 K under a driving current of 200 mA.
PMID- 28498822
TI - Interleukin-4 and interleukin-13 increase NADPH oxidase 1-related proliferation
of human colon cancer cells.
AB - Human colon cancers express higher levels of NADPH oxidase 1 [NOX1] than adjacent
normal epithelium. It has been suggested that reactive oxygen species [ROS]
derived from NOX1 contribute to DNA damage and neoplastic transformation in the
colon, particularly during chronic inflammatory stress. However, the mechanism(s)
underlying increased NOX1 expression in malignant tumors or chronic inflammatory
states involving the intestine are poorly characterized. We examined the effects
of two pro-inflammatory cytokines, IL-4 and IL-13, on the regulation of NOX1.
NOX1 expression was increased 4- to 5-fold in a time- and concentration-dependent
manner by both cytokines in human colon cancer cell lines when a functional Type
II IL-4 receptor was present. Increased NOX1 transcription following IL-4/IL-13
exposure was mediated by JAK1/STAT6 signaling, was associated with a ROS-related
inhibition of protein tyrosine phosphatase activity, and was dependent upon
activation and specific binding of GATA3 to the NOX1 promoter. NOX1-mediated ROS
production increased cell cycle progression through S-phase leading to a
significant increase in cellular proliferation. Evaluation of twenty pairs of
surgically-resected colon cancers and their associated uninvolved adjacent
colonic epithelium demonstrated a significant increase in the active form of
NOX1, NOX1-L, in tumors compared to normal tissues, and a significant correlation
between the expression levels of NOX1 and the Type II IL-4 receptor in tumor and
the uninvolved colon. These studies imply that NOX1 expression, mediated by IL
4/IL-13, could contribute to an oxidant milieu capable of supporting the
initiation or progression of colonic cancer, suggesting a role for NOX1 as a
therapeutic target.
PMID- 28498824
TI - Sublimation-assisted graphene transfer technique based on small polyaromatic
hydrocarbons.
AB - Advances in the chemical vapor deposition (CVD) growth of graphene have made this
material a very attractive candidate for a number of applications including
transparent conductors, electronics, optoeletronics, biomedical devices and
energy storage. The CVD method requires transfer of graphene on a desired
substrate and this is most commonly accomplished with polymers. The removal of
polymer carriers is achieved with organic solvents or thermal treatment which
makes this approach inappropriate for application to plastic thin films such as
polyethylene terephthalate substrates. An ultraclean graphene transfer method
under mild conditions is highly desired. In this article, we report a naphthalene
assisted graphene transfer technique which provides a reliable route to residue
free transfer of graphene to both hard and flexible substrates. The quality of
the transferred graphene was characterized with atomic force microscopy, scanning
electron microscopy, and Raman spectroscopy. Field effect transistors, based on
the naphthalene-transfered graphene, were fabricated and characterized. This work
has the potential to broaden the applications of CVD graphene in fields where
ultraclean graphene and mild graphene transfer conditions are required.
PMID- 28498825
TI - Direct evidence of barrier inhomogeneities at metal/AlGaN/GaN interfaces using
nanoscopic electrical characterizations.
AB - The existence of barrier inhomogeneities at metal-semiconductor interfaces is
believed to be one of the reasons for the non-ideal behaviour of Schottky
contacts. In general, barrier inhomogeneities are modelled using a Gaussian
distribution of barrier heights of nanoscale patches having low and high barrier
heights, and the standard deviation of this distribution roughly estimates the
level of barrier inhomogeneities. In the present work, we provide direct
experimental evidence of barrier inhomogeneities by performing electrical
characterizations on individual nanoscale patches and, further, obtaining the
magnitude of these inhomogeneities. Localized current-voltage measurements on
individual nanoscale patches were performed using conducting atomic force
microscopy (CAFM) whereas surface potential variations on nanoscale dimensions
were investigated using Kelvin probe force microscopy (KPFM) measurements. The
CAFM measurements revealed the distribution of barrier heights, which is
attributed to surface potential variations at nanoscale dimensions, as obtained
from KPFM measurements. The present work is an effort to provide direct evidence
of barrier inhomogeneities, finding their origin and magnitude by combining CAFM
and KPFM techniques and correlating their findings.
PMID- 28498826
TI - Divergent Influences of Cardiovascular Disease Risk Factor Domains on Cognition
and Gray and White Matter Morphology.
AB - OBJECTIVE: Hypertension, diabetes, dyslipidemia, and obesity are associated with
preclinical alterations in cognition and brain structure; however, this often
comes from studies of comprehensive risk scores or single isolated factors. We
examined associations of empirically derived cardiovascular disease risk factor
domains with cognition and brain structure. METHODS: A total of 124 adults (age,
59.8 [13.1] years; 41% African American; 50% women) underwent neuropsychological
and cardiovascular assessments and structural magnetic resonance imaging.
Principal component analysis of nine cardiovascular disease risk factors resulted
in a four-component solution representing 1, cholesterol; 2, glucose
dysregulation; 3, metabolic dysregulation; and 4, blood pressure. Separate linear
regression models for learning, memory, executive functioning, and
attention/information processing were performed, with all components entered at
once, adjusting for age, sex, and education. MRI analyses included whole-brain
cortical thickness and tract-based fractional anisotropy adjusted for age and
sex. RESULTS: Higher blood pressure was associated with poorer learning (B =
0.19; p = .019), memory (B = -0.22; p = .005), and executive functioning
performance (B = -0.14; p = .031), and lower cortical thickness within the right
lateral occipital lobe. Elevated glucose dysregulation was associated with poorer
attention/information processing performance (B = -0.21; p = .006) and lower
fractional anisotropy in the right inferior and bilateral superior longitudinal
fasciculi. Cholesterol was associated with higher cortical thickness within left
caudal middle frontal cortex. Metabolic dysfunction was positively associated
with right superior parietal lobe, left inferior parietal lobe, and left
precuneus cortical thickness. CONCLUSIONS: Cardiovascular domains were associated
with distinct cognitive, gray, and white matter alterations and distinct age
groups. Future longitudinal studies may assist in identifying vulnerability
profiles that may be most important for individuals with multiple cardiovascular
disease risk factors.
PMID- 28498827
TI - The Accuracy of the Spot Sign and the Blend Sign for Predicting Hematoma
Expansion in Patients with Spontaneous Intracerebral Hemorrhage.
AB - BACKGROUND Hematoma expansion is associated with poor outcome in intracerebral
hemorrhage (ICH) patients. The spot sign and the blend sign are reliable tools
for predicting hematoma expansion in ICH patients. The aim of this study was to
compare the accuracy of the two signs in the prediction of hematoma expansion.
MATERIAL AND METHODS Patients with spontaneous ICH were screened for the presence
of the computed tomography angiography (CTA) spot sign and the non-contrast CT
(NCCT) blend sign within 6 hours after onset of symptoms. The sensitivity,
specificity, and positive and negative predictive values of the spot sign and the
blend sign in predicting hematoma expansion were calculated. The accuracy of the
spot sign and the blend sign in predicting hematoma expansion was analyzed by
receiver-operator analysis. RESULTS A total of 115 patients were enrolled in this
study. The spot sign was observed in 25 (21.74%) patients, whereas the blend sign
was observed in 22 (19.13%) patients. Of the 28 patients with hematoma expansion,
the CTA spot sign was found on admission CT scans in 16 (57.14%) and the NCCT
blend sign in 12 (42.86%), respectively. The sensitivity, specificity, positive
predictive value, and negative predictive value of the spot sign for predicting
hematoma expansion were 57.14%, 89.66%, 64.00%, and 86.67%, respectively. In
contrast, the sensitivity, specificity, positive predictive value, and negative
predictive value of the blend sign were 42.86%, 88.51%, 54.55%, and 82.80%,
respectively. The area under the curve (AUC) of the spot sign was 0.734, which
was higher than that of the blend sign (0.657). CONCLUSIONS Both the spot sign
and the blend sign seemed to be good predictors for hematoma expansion, and the
spot sign appeared to have better predictive accuracy.
PMID- 28498828
TI - KDM1A/LSD1 regulates the differentiation and maintenance of spermatogonia in
mice.
AB - The proper regulation of spermatogenesis is crucial to ensure the continued
production of sperm and fertility. Here, we investigated the function of the
H3K4me2 demethylase KDM1A/LSD1 during spermatogenesis in developing and adult
mice. Conditional deletion of Kdm1a in the testis just prior to birth leads to
fewer spermatogonia and germ cell loss before 3 weeks of age. These results
demonstrate that KDM1A is required for spermatogonial differentiation, as well as
germ cell survival, in the developing testis. In addition, inducible deletion of
Kdm1a in the adult testis results in the abnormal accumulation of meiotic
spermatocytes, as well as apoptosis and progressive germ cell loss. These results
demonstrate that KDM1A is also required during adult spermatogenesis.
Furthermore, without KDM1A, the stem cell factor OCT4 is ectopically maintained
in differentiating germ cells. This requirement for KDM1A is similar to what has
been observed in other stem cell populations, suggesting a common function. Taken
together, we propose that KDM1A is a key regulator of spermatogenesis and germ
cell maintenance in the mouse.
PMID- 28498830
TI - The influence of the Great East Japan earthquake on microscopic polyangiitis: A
retrospective observational study.
AB - BACKGROUND: Antineutrophil cytoplasmic antibody-associated vasculitis is
triggered by environmental factors, including silica dust exposure. Repeated
tsunami waves brought a large volume of silica-containing sludge inland after the
Great East Japan earthquake in 2011. We aimed to determine if the serious
disaster influenced the clinical features of the microscopic polyangiitis.
METHODS: This is an observational retrospective study conducted in a single
institute. A total of 43 patients were included based on the CHCC2012 criteria
for microscopic polyangiitis from 2007 to 2015. We used the Poisson regression
model to determine the incidence of microscopic polyangiitis within the annual
population of the medical district. The participants were selected during a 3
year period from before (N = 13) to after the disaster (N = 20). The differences
of parameters and the overall survival between the groups were analyzed. RESULTS:
The incidence of microscopic polyangiitis increased after the disaster (lambda =
17.4/million/year [95%CI: 7.66-39.6] before the disaster and lambda =
33.1/million/year [17.7-61.7] after the disaster, P = 0.044). A high Birmingham
Activity Score was associated with a high incidence of microscopic polyangiitis
after the disaster. The overall survival of the patients with microscopic
polyangiitis declined significantly after the disaster. CONCLUSIONS: The Great
East Japan earthquake influenced the development of the microscopic polyangiitis
in our restricted area. The patients who developed after the disaster had severe
symptoms and a high mortality rate.
PMID- 28498829
TI - Biotinidase deficiency: Genotype-biochemical phenotype association in Brazilian
patients.
AB - INTRODUCTION: The association between the BTD genotype and biochemical phenotype
[profound biotinidase deficiency (BD), partial BD or heterozygous activity] is
not always consistent. This study aimed to investigate the genotype-biochemical
phenotype association in patients with low biotinidase activity. METHODS: All
exons, the 5'UTR and the promoter of the BTD gene were sequenced in 72 Brazilian
individuals who exhibited low biotinidase activity. For each patient, the
expected biochemical phenotype based on the known genotype was compared with the
observed biochemical phenotype. Additional non-genetic factors that could affect
the biotinidase activity were also analysed. RESULTS: Most individuals were
identified by neonatal screening (n = 66/72). When consecutive results for the
same patient were compared, age, prematurity and neonatal jaundice appeared to
affect the level of biotinidase activity. The biochemical phenotype at the time
of the second blood collection changed in 11/22 patients compared to results from
the first sample. Three novel variants were found: c.1337T>C (p.L446P), c.1466A>G
(p.N489S) and c.962G>A (p.W321*). Some patients with the same genotype presented
different biochemical phenotypes. The expected and observed biochemical
phenotypes agreed in 68.5% of cases (concordant patients). The non-coding
variants c.-183G>A, c.-315A>G and c.-514C>T were present in heterozygosis in 5/17
discordant patients. In addition, c.-183G>A and c.-514C>T were also present in
10/37 concordant patients. CONCLUSIONS: The variants found in the promoter region
do not appear to have a strong impact on biotinidase activity. Since there is a
disparity between the BTD genotype and biochemical phenotype, and biotinidase
activity may be affected by both genetic and non-genetic factors, we suggest that
the diagnosis of BD should be based on more than one measurement of plasma
biotinidase activity. DNA analysis can be of additional relevance to
differentiate between partial BD and heterozygosity.
PMID- 28498831
TI - Dynamics of analyst forecasts and emergence of complexity: Role of information
disparity.
AB - We report complex phenomena arising among financial analysts, who gather
information and generate investment advice, and elucidate them with the help of a
theoretical model. Understanding how analysts form their forecasts is important
in better understanding the financial market. Carrying out big-data analysis of
the analyst forecast data from I/B/E/S for nearly thirty years, we find skew
distributions as evidence for emergence of complexity, and show how information
asymmetry or disparity affects financial analysts' forming their forecasts. Here
regulations, information dissemination throughout a fiscal year, and interactions
among financial analysts are regarded as the proxy for a lower level of
information disparity. It is found that financial analysts with better access to
information display contrasting behaviors: a few analysts become bolder and issue
forecasts independent of other forecasts while the majority of analysts issue
more accurate forecasts and flock to each other. Main body of our sample of
optimistic forecasts fits a log-normal distribution, with the tail displaying a
power law. Based on the Yule process, we propose a model for the dynamics of
issuing forecasts, incorporating interactions between analysts. Explaining nicely
empirical data on analyst forecasts, this provides an appealing instance of
understanding social phenomena in the perspective of complex systems.
PMID- 28498832
TI - Prenatal exposure to the Great Chinese Famine and mid-age hypertension.
AB - BACKGROUND: One of the most terrible famines last century was Great Chinese
Famine (GCF) in 1959~1961 when millions of people died from starving. Under
nutrition during famine between the Western and Eastern (Dutch Hungry vs. GCF)
was similar, while cardiovascular consequences might not be the same. Addressing
such questions may gain new insight into prevention of cardiovascular diseases.
METHODS: A retrospective cohort of 18,593 participants aged 43-49 years of old,
was from Suzhou, China. Logistic regression model was used to calculate the
relative risk (RR) of hypertension and corresponding 95% confidence interval
(CI). The multivariate RRs were adjusted for age, plasma glucose, triglyceride,
and cholesterol. RESULTS: The multivariate RRs of systolic and diastolic pressure
were not significantly elevated in the rural subgroups, but was higher in the
urban population born in the famine (systolic pressure adjust RR 1.382, 95% CI
1.235-1.545, diastolic pressure adjust RR 1.569, 95% CI 1.415-1.740). The risks
of hypertension were significantly higher among the urban subjects than that in
the rural subgroups (systolic hypertension adjust RR 2.915, 95% CI 2.616-3.249,
diastolic hypertension adjust RR 4.568, 95% CI 4.079-5.116). Percentile of
optimal diastolic pressure at mid-age was significantly lower in the urban
population prenatally exposed to the famine regardless of sexes. However, a
similar reduction of percentage of optimal systolic pressure was only seen in the
female, not the male population in the urban region. CONCLUSION: The data suggest
Asian genetic basis was not able to block famine-programmed vascular diseases as
that happened in Europe, and the programmed problems due to under-nutrition could
be reversed after birth. Protective mechanisms may be related to diet habits
before age of 30 years old, which is important contribution to early prevention
of hypertension.
PMID- 28498833
TI - Assessment of the quality of DNA from various formalin-fixed paraffin-embedded
(FFPE) tissues and the use of this DNA for next-generation sequencing (NGS) with
no artifactual mutation.
AB - Formalin-fixed, paraffin-embedded (FFPE) tissues used for pathological diagnosis
are valuable for studying cancer genomics. In particular, laser-capture
microdissection of target cells determined by histopathology combined with FFPE
tissue section immunohistochemistry (IHC) enables precise analysis by next
generation sequencing (NGS) of the genetic events occurring in cancer. The result
is a new strategy for a pathological tool for cancer diagnosis: 'microgenomics'.
To more conveniently and precisely perform microgenomics, we revealed by
systematic analysis the following three details regarding FFPE DNA compared with
paired frozen tissue DNA. 1) The best quality of FFPE DNA is obtained by tissue
fixation with 10% neutral buffered formalin for 1 day and heat treatment of
tissue lysates at 95 degrees C for 30 minutes. 2) IHC staining of FFPE tissues
decreases the quantity and quality of FFPE DNA to one-fourth, and antigen
retrieval (at 120 degrees C for 15 minutes, pH 6.0) is the major reason for this
decrease. 3) FFPE DNA prepared as described herein is sufficient for NGS. For non
mutated tissue specimens, no artifactual mutation occurs during FFPE preparation,
as shown by precise comparison of NGS of FFPE DNA and paired frozen tissue DNA
followed by validation. These results demonstrate that even FFPE tissues used for
routine clinical diagnosis can be utilized to obtain reliable NGS data if
appropriate conditions of fixation and validation are applied.
PMID- 28498834
TI - Expression of MYSM1 is associated with tumor progression in colorectal cancer.
AB - Colorectal cancer, the third most common cancer in both men and women, has
gradually increased in recent years. MYSM1has been investigated as a regulator of
hematopoiesis and lymphocyte development in human. It has been reported that some
tumor-related genes were modulated by MYSM1. However, its exact role in cancer
development remains unclear. Herein, we aimed to examine the expression level of
MYSM1 in tumor tissues and its correlation with clinicopathology and survivals of
patients with colorectal cancer (CRC).MYSM1expressions in tumor specimens
resected from 123 CRC patients were detected by immunochemistry and Western blot
analysis. The results showed that MYSM1 was significantly highly expressed in
carcinoma tissues compared with adjacent normal mucosa tissues (P<0.05).
Correlation analyses by Pearson's chi-square test demonstrated that MYSM1 in
tumors was positively correlated with tumor status (pathological assessment of
the primary tumor (pT, P<0.001), regional lymph nodes (pN, P = 0.013), distant
metastasis (pM, P<0.001)) and clinic stage (P<0.001); Whereas, MYSM1 was not
associated with tumor size of CRC patients and was positively associated with
tumor differentiation grade (P = 0.015). Patients with positiveMYSM1expression
showed poor survival compared with the MYSM1 negative group
(P<0.001).Simultaneously, multivariate Cox regression analysis indicated
thatMYSM1 expression in tumor cells was an independent factor for reduced overall
survival in CRC patients (P<0.001).Additionally,MYSM1 in CRC SW480 cells was
silenced by small interference RNA (siRNA) technology. Scratch assay and
Transwell assay showed that MYSM1 silencing decreased migration and invasion
abilities of SW480 cells. These data suggested that expression of MYSM1 was
associated with the progression of CRC and might be a potential biomarker for
clinical prognosis.
PMID- 28498835
TI - Is traditional male circumcision effective as an HIV prevention strategy?
Evidence from Lesotho.
AB - In many developing countries, male circumcision has been promoted as an effective
HIV prevention strategy, and medical randomized controlled trials have indeed
shown a causal link. However, there is limited empirical evidence to support this
conclusion in countries where individuals can voluntary opt for different types
of circumcision. The present study considers male circumcision in Lesotho, where
HIV prevalence is among the highest in the world (23%). Here, men can opt for one
of two types of circumcision: traditional male circumcision in initiation
schools, or the medical option in health clinics. This paper investigates whether
the former has medical effects on individual HIV status that are as beneficial as
those shown for the latter. Controlling for the potential individual behavioral
response after the operation, it was found that circumcision performed in
initiation schools wholly offset the medical benefits of the surgical procedure.
This supports anecdotal evidence that the operation performed by traditional
circumcisers does not have the same protective effect against HIV transmission as
the medical operation. No evidence of "disinhibition" behavior among circumcised
men was found, nor differential risky sexual behavior among men circumcised,
traditionally or medically. Considering that, in Lesotho, traditional male
circumcision is undertaken by more than 90% of circumcised men, the findings
highlight the need for further research into how the operation in initiation
schools is performed and its medical benefits.
PMID- 28498836
TI - Mutations in COL1A1 and COL1A2 and dental aberrations in children and adolescents
with osteogenesis imperfecta - A retrospective cohort study.
AB - Osteogenesis imperfecta (OI) is a heterogeneous group of disorders of connective
tissue, caused mainly by mutations in the collagen I genes (COL1A1 and COL1A2).
Dentinogenesis imperfecta (DGI) and other dental aberrations are common features
of OI. We investigated the association between collagen I mutations and DGI,
taurodontism, and retention of permanent second molars in a retrospective cohort
of 152 unrelated children and adolescents with OI. The clinical examination
included radiographic evaluations. Teeth from 81 individuals were available for
histopathological evaluation. COL1A1/2 mutations were found in 104 individuals by
nucleotide sequencing. DGI was diagnosed clinically and radiographically in 29%
of the individuals (44/152) and through isolated histological findings in another
19% (29/152). In the individuals with a COL1A1 mutation, 70% (7/10) of those with
a glycine substitution located C-terminal of p.Gly305 exhibited DGI in both
dentitions while no individual (0/7) with a mutation N-terminal of this point
exhibited DGI in either dentition (p = 0.01). In the individuals with a COL1A2
mutation, 80% (8/10) of those with a glycine substitution located C terminal of
p.Gly211 exhibited DGI in both dentitions while no individual (0/5) with a
mutation N-terminal of this point (p = 0.007) exhibited DGI in either dentition.
DGI was restricted to the deciduous dentition in 20 individuals. Seventeen had
missense mutations where glycine to serine was the most prevalent substitution
(53%). Taurodontism occurred in 18% and retention of permanent second molars in
31% of the adolescents. Dental aberrations are strongly associated with
qualitatively changed collagen I. The varying expressivity of DGI is related to
the location of the collagen I mutation. Genotype information may be helpful in
identifying individuals with OI who have an increased risk of dental aberrations.
PMID- 28498837
TI - Whitefly attraction to rosemary (Rosmarinus officinialis L.) is associated with
volatile composition and quantity.
AB - Whitefly (Bemisia tabaci) is an important insect pest, causing severe damage to
agricultural crops. The pest was recorded in a commercial rosemary (Rosmarinus
officinalis, Lamiaceae) field, colonizing rosemary variety (var.) '2', but not
'11'. A series of field and controlled laboratory choice bioassays confirmed the
observed phenomenon. Mature potted plants of the two varieties were randomly
organized in a lemon verbena (Lippia citrodora) and lemon grass (Cymbopogon spp.)
fields. Seven days later var. '2' was significantly more colonized by whiteflies
than var. '11'. Under lab conditions, whiteflies were significantly more
attracted to var. '2' plantlets than to var. '11' following choice bioassays.
Furthermore, cotton plants dipped in an essential oil emulsion of var. '2' had
significantly greater colonization than cotton plants dipped in the essential oil
emulsion of var. '11'. Similar results were obtained in 'plant-plant', 'plant-no
plant' as well as, 'essential oil-essential oil' choice bioassay designs.
Analyses of the essential oils of the two varieties identified a set of common
and unique volatiles in each variety. Among these volatiles were beta
caryophyllene and limonene, two compounds known to be associated with plant
insect interactions. The attraction of B. tabaci to pure (>95%) beta
caryophyllene and limonene using a range of concentrations was examined in vitro
by choice bioassays. The compounds were attractive to the insect at moderate
concentration, but not at the lowest or highest concentrations used, where the
insect was not attracted or repelled, respectively. Limonene attracted the
insects at rates that were 10-fold lower than beta-caryophyllene. The results
emphasized the role of host plant volatiles in shaping the structure of B. tabaci
populations in nature and in agricultural systems, and provided insights into the
factors that contribute to the development of insect populations with unique
characteristics. The results could also serve for future development of bio
pesticides and in breeding programs.
PMID- 28498839
TI - Estimating nutrient uptake requirements for soybean using QUEFTS model in China.
AB - Estimating balanced nutrient requirements for soybean (Glycine max [L.] Merr) in
China is essential for identifying optimal fertilizer application regimes to
increase soybean yield and nutrient use efficiency. We collected datasets from
field experiments in major soybean planting regions of China between 2001 and
2015 to assess the relationship between soybean seed yield and nutrient uptake,
and to estimate nitrogen (N), phosphorus (P), and potassium (K) requirements for
a target yield of soybean using the quantitative evaluation of the fertility of
tropical soils (QUEFTS) model. The QUEFTS model predicted a linear-parabolic
plateau curve for the balanced nutrient uptake with a target yield increased from
3.0 to 6.0 t ha-1 and the linear part was continuing until the yield reached
about 60-70% of the potential yield. To produce 1000 kg seed of soybean in China,
55.4 kg N, 7.9 kg P, and 20.1 kg K (N:P:K = 7:1:2.5) were required in the above
ground parts, and the corresponding internal efficiencies (IE, kg seed yield per
kg nutrient uptake) were 18.1, 126.6, and 49.8 kg seed per kg N, P, and K,
respectively. The QUEFTS model also simulated that a balanced N, P, and K removal
by seed which were 48.3, 5.9, and 12.2 kg per 1000 kg seed, respectively,
accounting for 87.1%, 74.1%, and 60.8% of the total above-ground parts,
respectively. These results were conducive to make fertilizer recommendations
that improve the seed yield of soybean and avoid excessive or deficient nutrient
supplies. Field validation indicated that the QUEFTS model could be used to
estimate nutrient requirements which help develop fertilizer recommendations for
soybean.
PMID- 28498838
TI - Assessing medical professionalism: A systematic review of instruments and their
measurement properties.
AB - BACKGROUND: Over the last three decades, various instruments were developed and
employed to assess medical professionalism, but their measurement properties have
yet to be fully evaluated. This study aimed to systematically evaluate these
instruments' measurement properties and the methodological quality of their
related studies within a universally acceptable standardized framework and then
provide corresponding recommendations. METHODS: A systematic search of the
electronic databases PubMed, Web of Science, and PsycINFO was conducted to
collect studies published from 1990-2015. After screening titles, abstracts, and
full texts for eligibility, the articles included in this study were classified
according to their respective instrument's usage. A two-phase assessment was
conducted: 1) methodological quality was assessed by following the COnsensus
based Standards for the selection of health status Measurement INstruments
(COSMIN) checklist; and 2) the quality of measurement properties was assessed
according to Terwee's criteria. Results were integrated using best-evidence
synthesis to look for recommendable instruments. RESULTS: After screening 2,959
records, 74 instruments from 80 existing studies were included. The overall
methodological quality of these studies was unsatisfactory, with reasons
including but not limited to unknown missing data, inadequate sample sizes, and
vague hypotheses. Content validity, cross-cultural validity, and criterion
validity were either unreported or negative ratings in most studies. Based on
best-evidence synthesis, three instruments were recommended: Hisar's instrument
for nursing students, Nurse Practitioners' Roles and Competencies Scale, and
Perceived Faculty Competency Inventory. CONCLUSION: Although instruments
measuring medical professionalism are diverse, only a limited number of studies
were methodologically sound. Future studies should give priority to
systematically improving the performance of existing instruments and to
longitudinal studies.
PMID- 28498840
TI - A third generation vaccine for human visceral leishmaniasis and post kala azar
dermal leishmaniasis: First-in-human trial of ChAd63-KH.
AB - BACKGROUND: Visceral leishmaniasis (VL or kala azar) is the most serious form of
human leishmaniasis, responsible for over 20,000 deaths annually, and post kala
azar dermal leishmaniasis (PKDL) is a stigmatizing skin condition that often
occurs in patients after successful treatment for VL. Lack of effective or
appropriately targeted cell mediated immunity, including CD8+ T cell responses,
underlies the progression of VL and progression to PKDL, and can limit the
therapeutic efficacy of anti-leishmanial drugs. Hence, in addition to the need
for prophylactic vaccines against leishmaniasis, the development of therapeutic
vaccines for use alone or in combined immuno-chemotherapy has been identified as
an unmet clinical need. Here, we report the first clinical trial of a third
generation leishmaniasis vaccine, developed intentionally to induce Leishmania
specific CD8+ T cells. METHODS: We conducted a first-in-human dose escalation
Phase I trial in 20 healthy volunteers to assess the safety, tolerability and
immunogenicity of a prime-only adenoviral vaccine for human VL and PKDL. ChAd63
KH is a replication defective simian adenovirus expressing a novel synthetic gene
(KH) encoding two Leishmania proteins KMP-11 and HASPB. Uniquely, the latter was
engineered to reflect repeat domain polymorphisms and arrangements identified
from clinical isolates. We monitored innate immune responses by whole blood RNA
Seq and antigen specific CD8+ T cell responses by IFNgamma ELISPOT and
intracellular flow cytometry. FINDINGS: ChAd63-KH was safe at intramuscular doses
of 1x1010 and 7.5x1010 vp. Whole blood transcriptomic profiling indicated that
ChAd63-KH induced innate immune responses characterized by an interferon
signature and the presence of activated dendritic cells. Broad and quantitatively
robust CD8+ T cell responses were induced by vaccination in 100% (20/20) of
vaccinated subjects. CONCLUSION: The results of this study support the further
development of ChAd63-KH as a novel third generation vaccine for VL and PKDL.
TRIAL REGISTRATION: This clinical trial (LEISH1) was registered at EudraCT (2012
005596-14) and ISRCTN (07766359).
PMID- 28498841
TI - Awareness and attitudes towards anthrax and meat consumption practices among
affected communities in Zambia: A mixed methods approach.
AB - BACKGROUND: In Zambia, human anthrax cases often occur following cases of animal
anthrax. Human behaviour has been implicated in this transmission. The objective
of the study was to explore human behavioural patterns that may contribute to
outbreaks of anthrax among affected communities. METHODS: A mixed methods study
was conducted in four districts of Zambia from November 2015 to February 2016. A
cross sectional survey involving 1,127 respondents, six focus group discussions
and seven key informant interviews with professional staff were conducted.
Descriptive statistics on socio-demographic characteristics, awareness of
anthrax, attitudes towards cattle vaccination and risk factors for anthrax and
vaccination practices were run using STATA 12 for analysis. RESULTS: Overall, 88%
of respondents heard about anthrax, 85.1% were aware that anthrax is transmitted
by eating infected meat and 64.2% knew that animals and humans can be infected
with anthrax. However, qualitative data suggested that awareness of anthrax
varied across communities. Qualitative findings also indicated that, in Western
and Muchinga provinces, human anthrax was transmitted by eating infected beef and
hippo (Hippopotamus amphibious) meat, respectively. Although survey data
indicated that 62.2% of respondents vaccinated their animals, qualitative
interviews and annual vaccination reports indicated low vaccination rates, which
were attributed to inadequate veterinary service provision and logistical
challenges. While 82% of respondents indicated that they reported animal deaths
to veterinary officers, only 13.5% of respondents buried infected carcasses.
Majority (78.1%) of respondents either ate, sold or shared meat from dead animals
with other community members. Poverty, lack of access to meat protein and
economic reasons were cited as drivers for consuming infected meat. CONCLUSIONS:
Health education campaigns must be intensified to reduce the risk of human
exposure. Veterinary extension services should be strengthened and cold chain
facilities decentralized in order to improve accessibility to anthrax vaccine. It
is also important to involve the affected communities and collaborate with other
disciplines in order to effectively tackle poverty, improve veterinary services
and address inherent meat consumption practices within the communities.
PMID- 28498842
TI - Prognostic significance and predictors of the system inflammation score in
ovarian clear cell carcinoma.
AB - Chronic inflammation is a well-known epidemiologic factor of ovarian clear cell
carcinomas (OCCC), but has an uncertain role in prognosis. We developed a
systemic inflammation score (SIS) based on preoperative serum albumin and
neutrophil-to-lymphocyte ratio (NLR) for predicting progression-free survival
(PFS) and overall survival (OS) in OCCC patients. A retrospective review was
performed in 155 patients with OCCC undergoing primary debulking and chemotherapy
at a single institute between 1995 and 2010. Cox regression models were fitted to
analyze the effect of prognostic factors on PFS and OS. Harrell's concordance
index was calculated to assess predictive accuracy. The SIS consisting of serum
albumin and NLR was retained as an independent indicator adjusting for
traditional clinicopathological features. A high SIS was significantly associated
with aggressive tumor behavior, platinum resistance, and served as an independent
predictor of reduced PFS (P = 0.006) and OS (P = 0.019). The SIS had a good
discrimination ability for the predictive PFS (c-index = 0.712) and OS (c-index =
0.722). We have developed a system inflammation score for predicting prognosis of
OCCC patients, which may help stratify patients for postsurgical management.
PMID- 28498843
TI - When Bitcoin encounters information in an online forum: Using text mining to
analyse user opinions and predict value fluctuation.
AB - Bitcoin is an online currency that is used worldwide to make online payments. It
has consequently become an investment vehicle in itself and is traded in a way
similar to other open currencies. The ability to predict the price fluctuation of
Bitcoin would therefore facilitate future investment and payment decisions. In
order to predict the price fluctuation of Bitcoin, we analyse the comments posted
in the Bitcoin online forum. Unlike most research on Bitcoin-related online
forums, which is limited to simple sentiment analysis and does not pay sufficient
attention to note-worthy user comments, our approach involved extracting keywords
from Bitcoin-related user comments posted on the online forum with the aim of
analytically predicting the price and extent of transaction fluctuation of the
currency. The effectiveness of the proposed method is validated based on Bitcoin
online forum data ranging over a period of 2.8 years from December 2013 to
September 2016.
PMID- 28498844
TI - Windowed persistent homology: A topological signal processing algorithm applied
to clinical obesity data.
AB - Overweight and obesity are highly prevalent in the population of the United
States, affecting roughly 2/3 of Americans. These diseases, along with their
associated conditions, are a major burden on the healthcare industry in terms of
both dollars spent and effort expended. Volitional weight loss is attempted by
many, but weight regain is common. The ability to predict which patients will
lose weight and successfully maintain the loss versus those prone to regain
weight would help ease this burden by allowing clinicians the ability to skip
treatments likely to be ineffective. In this paper we introduce a new windowed
approach to the persistent homology signal processing algorithm that, when paired
with a modified, semimetric version of the Hausdorff distance, can differentiate
the two groups where other commonly used methods fail. The novel approach is
tested on accelerometer data gathered from an ongoing study at the University of
Michigan. While most standard approaches to signal processing show no difference
between the two groups, windowed persistent homology and the modified Hausdorff
semimetric show a clear separation. This has significant implications for
clinical decision making and patient care.
PMID- 28498845
TI - Measurement of tissue azithromycin levels in self-collected vaginal swabs post
treatment using liquid chromatography and tandem mass spectrometry (LC-MS/MS).
AB - BACKGROUND: Azithromycin is recommended for the treatment of uncomplicated
urogenital chlamydia infection although the standard 1gram dose sometimes fails
to eradicate the infection (treatment failure). One hypothesis proposed for
treatment failure has been insufficient levels of the antibiotic at the site of
infection. We developed an assay using liquid chromatography and tandem mass
spectrometry (LC-MS/MS) to measure azithromycin concentration in high-vaginal
swabs and monitor how concentration changes over time following routine
azithromycin treatment. METHODS: Azithromycin concentrations were measured in two
groups of women either within the first 24h of taking a 1g dose (N = 11) or over
9 days (N = 10). Azithromycin concentrations were normalised to an internal
standard (leucine enkephalin), and the bulk lipid species phosphatidylcholine
[PC(34:1)], using an Agilent 6490 triple quadrupole instrument in positive
ionisation mode. The abundances of azithromycin, PC(34:1), and leu-enkephalin
were determined by multiple reaction monitoring and absolute levels of
azithromycin estimated using standard curves prepared on vaginal specimens.
RESULTS: Vaginal azithromycin concentrations of women were rapidly obtained after
5h post-treatment (mean concentration = 1031mcg/mg of lipid, range = 173
2693mcg/mg). In women followed for 9 days, peak concentrations were highest after
day 2 (mean concentration = 2206mcg/mg, range = 721-5791mcg/mg), and remained
high for at least 9 days with a mean concentration of 384mcg/mg (range = 139
1024mcg/mg) on day 9. CONCLUSION: Our study confirmed that a single 1g dose of
azithromycin is rapidly absorbed and remains in the vagina at relatively high
levels for at least a week, suggesting that poor antibiotic absorption is
unlikely to be an explanation for treatment failure.
PMID- 28498846
TI - MeCP2 recognizes cytosine methylated tri-nucleotide and di-nucleotide sequences
to tune transcription in the mammalian brain.
AB - Mutations in the gene encoding the methyl-CG binding protein MeCP2 cause several
neurological disorders including Rett syndrome. The di-nucleotide methyl-CG (mCG)
is the classical MeCP2 DNA recognition sequence, but additional methylated
sequence targets have been reported. Here we show by in vitro and in vivo
analyses that MeCP2 binding to non-CG methylated sites in brain is largely
confined to the tri-nucleotide sequence mCAC. MeCP2 binding to chromosomal DNA in
mouse brain is proportional to mCAC + mCG density and unexpectedly defines large
genomic domains within which transcription is sensitive to MeCP2 occupancy. Our
results suggest that MeCP2 integrates patterns of mCAC and mCG in the brain to
restrain transcription of genes critical for neuronal function.
PMID- 28498848
TI - Modulation of the growth and metabolic response of cyanobacteria by the
multifaceted activity of naringenin.
AB - The interactions between the plant-derived bioflavonoid, naringenin, and
prokaryotic microalgae representatives (cyanobacteria), were investigated with
respect to its influence on the growth and metabolic response of these
microorganisms. To achieve reliable results, the growth of cyanobacteria was
determined based on measurements of chlorophyll content, morphological changes
were assessed through microscopic observations, and the chemical response of
cells was determined using liquid and gas chromatography (HPLC; GC-FID). The
results show that micromolar levels of naringenin stimulated the growth of
cyanobacteria. Increased growth was observed for halophilic strains at naringenin
concentrations below 40 mg L-1, and in freshwater strains at concentrations below
20 mg L-1. The most remarkable stimulation was observed for the freshwater
species Nostoc muscorum, which had a growth rate that was up to 60% higher than
in the control. When naringenin was examined at concentrations above 40 mg L-1,
the growth of the tested microorganisms was inhibited. Simultaneously, an
intensive excretion of exopolysaccharides was observed. Microscopic observations
strongly suggest that these effects resulted from a structural disturbance of
cyanobacterial cell walls that was exerted by naringenin. This phenomenon, in
combination with the absorption of naringenin into cell wall structures,
influenced cell permeability and thus the growth of bacteria. Fortunately, almost
all the naringenin added to the culture was incorporated into to cell
substructures and could be recovered through extraction, raising the possibility
that this modulator could be recycled.
PMID- 28498847
TI - Paradoxical myeloid-derived suppressor cell reduction in the bone marrow of SIV
chronically infected macaques.
AB - Myeloid derived suppressor cells (MDSCs), which suppress anti-tumor or anti-viral
immune responses, are expanded in the peripheral blood and tissues of
patients/animals with cancer or viral infectious diseases. We here show that in
chronic SIV infection of Indian rhesus macaques, the frequency of MDSCs in the
bone marrow (BM) was paradoxically and unexpectedly decreased, but increased in
peripheral blood. Reduction of BM MDSCs was found in both CD14+MDSC and Lin
CD15+MDSC subsets. The reduction of MDSCs correlated with high plasma viral loads
and low CD4+ T cell counts, suggesting that depletion of BM MDSCs was associated
with SIV/AIDS disease progression. Of note, in SHIVSF162P4-infected macaques,
which naturally control viral replication within a few months of infection, the
frequency of MDSCs in the bone marrow was unchanged. To investigate the
mechanisms by which BM MDSCs were reduced during chronic SIV infection, we tested
several hypotheses: depletion due to viral infection, alterations in MDSC
trafficking, and/or poor MDSC replenishment. We found that the possible
mobilization of MDSCs from BM to peripheral tissues and the slow self
replenishment of MDSCs in the BM, along with the viral infection-induced
depletion, all contribute to the observed BM MDSC reduction. We first demonstrate
MDSC SIV infection in vivo. Correlation between BM CD14+MDSC reduction and CD8+ T
cell activation in tissues is consistent with decreased immune suppression by
MDSCs. Thus, depletion of BM MDSCs may contribute to the pathologic immune
activation during chronic SIV infection and by extension HIV infection.
PMID- 28498849
TI - Percutaneous coronary intervention with second-generation drug-eluting stent
versus bare-metal stent: Systematic review and cost-benefit analysis.
AB - BACKGROUND: Drug-eluting stents (DESs) were considered as ground-breaking
technology promising to eradicate restenosis and the necessity to perform
multiple revascularization procedures subsequent to percutaneous coronary
intervention. Soon after DESs were released on the market, however, there were
reports of a potential increase in mortality and of early or late thrombosis. In
addition, DESs are far more expensive than bare-metal stents (BMSs), which has
led to their limited use in many countries. The technology has improved over the
last few years with the second generation of DESs (DES-2). Moreover, costs have
come down and an improved safety profile with decreased thrombosis has been
reported. OBJECTIVE: Perform a cost-benefit analysis of DES-2s versus BMSs in the
context of a publicly funded university hospital in Quebec, Canada. METHODS: A
systematic review of meta-analyses was conducted between 2012 and 2016 to extract
data on clinical effectiveness. The clinical outcome of interest for the cost
benefit analysis was target-vessel revascularization (TVR). Cost units are those
used in the Quebec health-care system. The cost-benefit analysis was based on a 2
year perspective. Deterministic and stochastic models (discrete-event simulation)
were used, and various risk factors of reintervention were considered. RESULTS:
DES-2s are much more effective than BMSs with respect to TVR rate ratio (i.e.,
0.29 to 0.62 in more recent meta-analyses). DES-2s seem to cause fewer deaths and
in-stent thrombosis than BMSs, but results are rarely significant, with the
exception of the cobalt-chromium everolimus DES. The rate ratio of myocardial
infraction is systematically in favor of DES-2s and very often significant.
Despite the higher cost of DES-2s, fewer reinterventions can lead to huge savings
(i.e., -$479 to -$769 per patient). Moreover, the higher a patient's risk of
reintervention, the higher the savings associated with the use of DES-2s.
CONCLUSION: Despite the higher purchase cost of DES-2s compared to BMSs,
generalizing their use, in particular for patients at high risk of
reintervention, should enable significant savings.
PMID- 28498850
TI - Genome-wide transcriptome profiling of radish (Raphanus sativus L.) in response
to vernalization.
AB - Vernalization is a key process for premature bolting. Although many studies on
vernalization have been reported, the molecular mechanism of vernalization is
still largely unknown in radish. In this study, we sequenced the transcriptomes
of radish seedlings at three different time points during vernalization. More
than 36 million clean reads were generated for each sample and the portions
mapped to the reference genome were all above 67.0%. Our results show that the
differentially expressed genes (DEGs) between room temperature and the early
stage of vernalization (4,845) are the most in all treatments pairs. A series of
vernalization related genes, including two FLOWERING LOCUS C (FLC) genes, were
screened according to the annotations. A total of 775 genes were also filtered as
the vernalization related candidates based on their expression profiles. Cold
stress responsive genes were also analyzed to further confirm the sequencing
result. Several key genes in vernalization or cold stress response were validated
by quantitative RT-PCR (RT-qPCR). This study identified a number of genes that
may be involved in vernalization, which are useful for other functional genomics
research in radish.
PMID- 28498851
TI - Myopia and depressive symptoms among older Chinese adults.
AB - PURPOSE: Few population-based data support the hypothesis that refractive errors
are associated with depressive symptoms. We aim to assess the impact of myopia on
the risk of having depressive symptoms in a community-based cohort of elderly
Chinese. METHODS: A community-based cross-sectional study of 4611 Chinese adults
aged 60 years or older was conducted. Depressive symptoms were measured using the
9-item Patient Health Questionnaire (PHQ-9) depression scale in 4597 adults.
Refraction was determined by auto-refraction followed by subjective refraction.
Myopia was defined as spherical equivalent (SE) < -0.50 diopters (D) and high
myopia as SE < -6.00 D. RESULTS: After adjusting for age, gender, education,
lifestyle-related exposures, presenting visual acuity and age-related cataract,
myopic adults were more likely to have any depressive symptoms compared with non
myopic ones (odds ratio = 1.39; 95% confidence interval 1.04, 1.92). There were
no significant differences in the risk of having any depressive symptoms between
those with and without high myopia. Myopia or high myopia was not associated with
having moderate depressive symptoms. The impact of myopia on depressive symptoms
was stronger in adults with no formal education compared with those with formal
education. CONCLUSIONS: Myopia was related with the presence of depressive
symptoms among older adults.
PMID- 28498852
TI - Ultra high-field (7tesla) magnetic resonance spectroscopy in Amyotrophic Lateral
Sclerosis.
AB - The main objective of this study was to utilize high field (7T) in vivo proton
magnetic resonance imaging to increase the ability to detect metabolite changes
in people with ALS, specifically, to quantify levels of glutamine and glutamine
separately. The second objective of this study was to correlate metabolic markers
with clinical outcomes of disease progression. 13 ALS participants and 12 age
matched healthy controls (HC) underwent 7 Tesla MRI and MRS. Single voxel MR
spectra were acquired from the left precentral gyrus using a very short echo time
(TE = 5 ms) STEAM sequence. MRS data was quantified using LCModel and correlated
to clinical outcome markers. N-acetylaspartate (NAA) and total NAA (tNA, NAA +
NAAG) were decreased by 17% in people with ALS compared to HC (P = 0.004 and P =
0.005, respectively) indicating neuronal injury and/or loss in the precentral
gyrus. tNA correlated with disease progression as measured by forced vital
capacity (FVC) (P = 0.014; Rrho = 0.66) and tNA/tCr correlated with overall
functional decline as measured by worsening of the ALS Functional Rating Scale
Revised (ALSFRS-R) (P = 0.004; Rrho = -0.74). These findings underscore the
importance of NAA as a reliable biomarker for neuronal injury and disease
progression in ALS. Glutamate (Glu) was 15% decreased in people with ALS compared
to HC (P = 0.02) while glutamine (Gln) concentrations were similar between the
two groups. Furthermore, the decrease in Glu correlated with the decrease in FVC
(P = 0.013; Rrho = 0.66), a clinical marker of disease progression. The decrease
in Glu is most likely driven by intracellular Glu loss due to neuronal loss and
degeneration. Neither choline containing components (Cho), a marker for cell
membrane turnover, nor myo-Inositol (mI), a suspected marker for
neuroinflammation, showed significant differences between the two groups.
However, mI/tNA was correlated with upper motor neuron burden (P = 0.004, Rrho =
0.74), which may reflect a relative increase of activated microglia around motor
neurons. In summary, 7T 1H MRS is a powerful non-invasive imaging technique to
study molecular changes related to neuronal injury and/or loss in people with
ALS.
PMID- 28498853
TI - Safety and immunogenicity of an inactivated whole cell tuberculosis vaccine
booster in adults primed with BCG: A randomized, controlled trial of DAR-901.
AB - BACKGROUND: Development of a tuberculosis vaccine to boost BCG is a major
international health priority. SRL172, an inactivated whole cell booster derived
from a non-tuberculous mycobacterium, is the only new vaccine against
tuberculosis to have demonstrated efficacy in a Phase 3 trial. In the present
study we sought to determine if a three-dose series of DAR-901 manufactured from
the SRL172 master cell bank by a new, scalable method was safe and immunogenic.
METHODS: We performed a single site, randomized, double-blind, controlled, Phase
1 dose escalation trial of DAR-901 at Dartmouth-Hitchcock Medical Center in the
United States. Healthy adult subjects age 18-65 with prior BCG immunization and a
negative interferon-gamma release assay (IGRA) were enrolled in cohorts of 16
subjects and randomized to three injections of DAR-901 (n = 10 per cohort), or
saline placebo (n = 3 per cohort), or two injections of saline followed by an
injection of BCG (n = 3 per cohort; 1-8 x 106 CFU). Three successive cohorts were
enrolled representing DAR-901 at 0.1, 0.3, and 1 mg per dose. Randomization was
performed centrally and treatments were masked from staff and volunteers.
Subsequent open label cohorts of HIV-negative/IGRA-positive subjects (n = 5) and
HIV-positive subjects (n = 6) received three doses of 1 mg DAR-901. All subjects
received three immunizations at 0, 2 and 4 months administered as 0.1 mL
injections over the deltoid muscle alternating between right and left arms. The
primary outcomes were safety and immunogenicity. Subjects were followed for 6
months after dose 3 for safety and had phlebotomy performed for safety studies
and immune assays before and after each injection. Immune assays using peripheral
blood mononuclear cells included cell-mediated IFN-gamma responses to DAR-901
lysate and to Mycobacterium tuberculosis (MTB) lysate; serum antibody to M.
tuberculosis lipoarabinomannan was assayed by ELISA. RESULTS: DAR-901 had an
acceptable safety profile and was well-tolerated at all dose levels in all
treated subjects. No serious adverse events were reported. Median (range) 7-day
erythema and induration at the injection site for 1 mg DAR-901 were 10 (4-20) mm
and 10 (4-16) mm, respectively, and for BCG, 30 (10-107) mm and 38 (15-55) mm,
respectively. Three mild AEs, all headaches, were considered possibly related to
DAR-901. No laboratory or vital signs abnormalities were related to immunization.
Compared to pre-vaccination responses, three 1 mg doses of DAR-901 induced
statistically significant increases in IFN-gamma response to DAR-901 lysate and
MTB lysate, and in antibody responses to M. tuberculosis lipoarabinomannan. Ten
subjects who received 1 mg DAR-901 remained IFN-gamma release assay (IGRA)
negative after three doses of vaccine. CONCLUSIONS: A three-injection series of
DAR-901 was well-tolerated, had an acceptable safety profile, and induced
cellular and humoral immune responses to mycobacterial antigens. DAR-901 is
advancing to efficacy trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT02063555.
PMID- 28498855
TI - Reversible integer wavelet transform for blind image hiding method.
AB - In this article, a blind data hiding reversible methodology to embed the secret
data for hiding purpose into cover image is proposed. The key advantage of this
research work is to resolve the privacy and secrecy issues raised during the data
transmission over the internet. Firstly, data is decomposed into sub-bands using
the integer wavelets. For decomposition, the Fresnelet transform is utilized
which encrypts the secret data by choosing a unique key parameter to construct a
dummy pattern. The dummy pattern is then embedded into an approximated sub-band
of the cover image. Our proposed method reveals high-capacity and great
imperceptibility of the secret embedded data. With the utilization of family of
integer wavelets, the proposed novel approach becomes more efficient for hiding
and retrieving process. It retrieved the secret hidden data from the embedded
data blindly, without the requirement of original cover image.
PMID- 28498856
TI - Patterns of intravenous fluid resuscitation use in adult intensive care patients
between 2007 and 2014: An international cross-sectional study.
AB - BACKGROUND: In 2007, the Saline versus Albumin Fluid Evaluation-Translation of
Research Into Practice Study (SAFE-TRIPS) reported that 0.9% sodium chloride
(saline) and hydroxyethyl starch (HES) were the most commonly used resuscitation
fluids in intensive care unit (ICU) patients. Evidence has emerged since 2007
that these fluids are associated with adverse patient-centred outcomes. Based on
the published evidence since 2007, we sought to determine the current type of
fluid resuscitation used in clinical practice and the predictors of fluid choice
and determine whether these have changed between 2007 and 2014. METHODS: In 2014,
an international, cross-sectional study was conducted (Fluid-TRIPS) to document
current patterns of intravenous resuscitation fluid use and determine factors
associated with fluid choice. We examined univariate and multivariate
associations between patients and prescriber characteristics, geographical region
and fluid type. Additionally, we report secular trends of resuscitation fluid use
in a cohort of ICUs that participated in both the 2007 and 2014 studies.
Regression analysis were conducted to determine changes in the administration of
crystalloid or colloid between 2007 and 2014. FINDINGS: In 2014, a total of 426
ICUs in 27 countries participated. Over the 24 hour study day, 1456/6707 (21.7%)
patients received resuscitation fluid during 2716 resuscitation episodes.
Crystalloids were administered to 1227/1456 (84.3%) patients during 2208/2716
(81.3%) episodes and colloids to 394/1456 (27.1%) patients during 581/2716
(21.4%) episodes. In multivariate analyses, practice significantly varied between
geographical regions. Additionally, patients with a traumatic brain injury were
less likely to receive colloid when compared to patients with no trauma (adjusted
OR 0.24; 95% CI 0.1 to 0.62; p = 0.003). Patients in the ICU for one or more days
where more likely to receive colloid compared to patients in the ICU on their
admission date (adjusted OR 1.75; 95% CI 1.27 to 2.41; p = <0.001). For secular
trends in fluid resuscitation, 84 ICUs in 17 countries contributed data. In 2007,
527/1663 (31.7%) patients received fluid resuscitation during 1167 episodes
compared to 491/1763 (27.9%) patients during 960 episodes in 2014. The use of
crystalloids increased from 498/1167 (42.7%) in 2007 to 694/960 (72.3%) in 2014
(odds ratio (OR) 3.75, 95% confidence interval (CI) 2.95 to 4.77; p = <0.001),
primarily due to a significant increase in the use of buffered salt solutions.
The use of colloids decreased from 724/1167 (62.0%) in 2007 to 297/960 (30.9%) in
2014 (OR 0.29, 95% CI 0.19 to 0.43; p = <0.001), primarily due to a decrease in
the use of HES, but an overall increase in the use of albumin. CONCLUSIONS:
Clinical practices of intravenous fluid resuscitation have changed between 2007
and 2014. Geographical location remains a strong predictor of the type of fluid
administered for fluid resuscitation. Overall, there is a preferential use of
crystalloids, specifically buffered salt solutions, over colloids. There is now
an imperative to conduct a trial determining the safety and efficacy of these
fluids on patient-centred outcomes. TRIAL REGISTRATION: Clinicaltrials.gov: Fluid
Translation of research into practice study (Fluid-TRIPS) NCT02002013.
PMID- 28498857
TI - Cost-effectiveness of pneumococcal vaccination strategies for the elderly in
Korea.
AB - BACKGROUND: Although the 13-valent pneumococcal conjugate vaccine (PCV13) showed
good efficacy against pneumococcal disease in the the CAPiTA trial, the 23-valent
pneumococcal polysaccharide vaccination (PPSV23) program has been ongoing for
older adults aged >= 65 years in Korea since May of 2013. This study aimed to
evaluate the cost-effectiveness of the current vaccination strategy (a single
dose PPSV23 vaccination) compared to a single-dose PCV13 vaccination and
sequential PCV13-PPSV23 vaccinations in the elderly population aged >= 65 years.
METHODS: Using a Markov model, the incremental cost-effectiveness ratios (ICERs)
of three vaccination strategies were assessed in a societal context. The
transition probabilities, utility weights to estimate quality adjusted life year
(QALY), and disease treatment costs were either calculated or cited from
published data and the Health Insurance Review and Assessment Service.
Simulations were performed in hypothetical cohorts of Korean adults aged >= 19
years. The vaccine effectiveness of PPSV23 was cited from a Cochrane Review
report, while PCV13 effectiveness data were gathered from the CAPiTA trial.
RESULTS: Current PPSV23 vaccination strategies were cost-effective (ICER, $25,786
per QALY). However, the administration of PCV13 as a substitute for PPSV23 was
shown to be more cost-effective than PPSV23 vaccination (ICER, $797 per QALY).
Sequential PCV13-PPSV23 vaccination was also more cost-effective than PPSV23 for
elderly people aged >= 65 years. In sensitivity analysis assuming significant
PPSV23 effectiveness (50%) against non-bacteremic pneumococcal pneumonia, the
PCV13 vaccination strategy was superior to the PPSV23 vaccination strategy in
terms of cost-effectiveness. CONCLUSION: The results suggest that PCV13
vaccination is more cost-effective in elderly subjects aged >= 65 years compared
to the current PPSV23 vaccination strategy. When complete data is obtained in
2018 on the maximal herd effects of childhood PCV13 immunization, the incidence
of pneumococcal pneumonia and the cost-effectiveness of vaccination strategies
need to be reassessed.
PMID- 28498854
TI - Single-trait and multi-trait genome-wide association analyses identify novel loci
for blood pressure in African-ancestry populations.
AB - Hypertension is a leading cause of global disease, mortality, and disability.
While individuals of African descent suffer a disproportionate burden of
hypertension and its complications, they have been underrepresented in genetic
studies. To identify novel susceptibility loci for blood pressure and
hypertension in people of African ancestry, we performed both single and multiple
trait genome-wide association analyses. We analyzed 21 genome-wide association
studies comprised of 31,968 individuals of African ancestry, and validated our
results with additional 54,395 individuals from multi-ethnic studies. These
analyses identified nine loci with eleven independent variants which reached
genome-wide significance (P < 1.25*10-8) for either systolic and diastolic blood
pressure, hypertension, or for combined traits. Single-trait analyses identified
two loci (TARID/TCF21 and LLPH/TMBIM4) and multiple-trait analyses identified one
novel locus (FRMD3) for blood pressure. At these three loci, as well as at
GRP20/CDH17, associated variants had alleles common only in African-ancestry
populations. Functional annotation showed enrichment for genes expressed in
immune and kidney cells, as well as in heart and vascular cells/tissues.
Experiments driven by these findings and using angiotensin-II induced
hypertension in mice showed altered kidney mRNA expression of six genes,
suggesting their potential role in hypertension. Our study provides new evidence
for genes related to hypertension susceptibility, and the need to study African
ancestry populations in order to identify biologic factors contributing to
hypertension.
PMID- 28498858
TI - Does stroke volume variation predict fluid responsiveness in children: A
systematic review and meta-analysis.
AB - OBJECTIVE: Stroke volume variation (SVV) is a reliable predictor of fluid
responsiveness in adult patients. However, the predictive value of SVV is
uncertain in pediatric patients. We performed the first systematic meta-analysis
to evaluate the diagnostic value of SVV in predicting fluid responsiveness in
children. METHODS: PUBMED, EMBASE, and Cochrane Central Register of Controlled
Trials were searched up to December 2016. Original studies assessing the
diagnostic accuracy of SVV in predicting fluid responsiveness in children were
considered to be eligible. A random-effects model was used to calculate pooled
values of sensitivity, specificity and diagnostic odds ratio with 95% CI. The
summary receiver operating characteristic curve was estimated and area under the
curve was calculated. Quality of the studies was assessed with the QUADAS-2 tool.
RESULTS: Six studies with a total of 279 fluid boluses in 224 children were
included. The analysis demonstrated a pooled sensitivity of 0.68 (95% CI,0.59
0.76), pooled specificity of 0.65 (95% CI, 0.57-0.73), pooled diagnostic odds
ratio of 8.24 (95% CI, 2.58-26.30), and the summary area under the summary
receiver operating characteristic curve of 0.81. However, significant inter-study
heterogeneity was found (p<0.05, I2 = 61.3%), likely due to small sample size and
diverse study characteristics. CONCLUSIONS: Current evidence suggests that SVV
was of diagnostic value in predicting fluid responsiveness in children under
mechanical ventilation. Given the high heterogeneity of published data, further
studies are needed to confirm the diagnostic accuracy of SVV in predicting fluid
responsiveness in pediatric patients.
PMID- 28498859
TI - USP9X counteracts differential ubiquitination of NPHP5 by MARCH7 and BBS11 to
regulate ciliogenesis.
AB - Ciliogenesis is a fundamental biological process central to human health.
Precisely how this process is coordinated with the cell cycle remains an open
question. We report that nephrocystin-5 (NPHP5/IQCB1), a positive regulator of
ciliogenesis, is a stable and low turnover protein subjected to cycles of
ubiquitination and deubiquitination. NPHP5 directly binds to a deubiquitinating
enzyme USP9X/FAM and two E3 ubiquitin ligases BBS11/TRIM32 and MARCH7/axotrophin.
NPHP5 undergoes K63 ubiquitination in a cell cycle dependent manner and K48/K63
ubiquitination upon USP9X depletion or inhibition. In the G0/G1/S phase, a pool
of cytoplasmic USP9X recruited to the centrosome by NPHP5 protects NPHP5 from
ubiquitination, thus favouring cilia assembly. In the G2/M phase, USP9X
dissociation from the centrosome allows BBS11 to K63 ubiquitinate NPHP5 which
triggers protein delocalization and loss of cilia. BBS11 is a resident
centrosomal protein, whereas cytoplasmic USP9X sequesters the majority of MARCH7
away from the centrosome during interphase. Depletion or inhibition of USP9X
leads to an accumulation of centrosomal MARCH7 which K48 ubiquitinates NPHP5,
triggering protein degradation and cilia loss. At the same time, BBS11 K63
ubiquitinates NPHP5. Our data suggest that dynamic ubiquitination and
deubiquitination of NPHP5 plays a crucial role in the regulation of ciliogenesis.
PMID- 28498860
TI - Genetic micro-epidemiology of malaria in Papua Indonesia: Extensive P. vivax
diversity and a distinct subpopulation of asymptomatic P. falciparum infections.
AB - BACKGROUND: Genetic analyses of Plasmodium have potential to inform on
transmission dynamics, but few studies have evaluated this on a local spatial
scale. We used microsatellite genotyping to characterise the micro-epidemiology
of P. vivax and P. falciparum diversity to inform malaria control strategies in
Timika, Papua Indonesia. METHODS: Genotyping was undertaken on 713 sympatric P.
falciparum and P. vivax isolates from a cross-sectional household survey and
clinical studies conducted in Timika. Standard population genetic measures were
applied, and the data was compared to published data from Kalimantan, Bangka,
Sumba and West Timor. RESULTS: Higher diversity (HE = 0.847 vs 0.625; p = 0.017)
and polyclonality (46.2% vs 16.5%, p<0.001) were observed in P. vivax versus P.
falciparum. Distinct P. falciparum substructure was observed, with two
subpopulations, K1 and K2. K1 was comprised solely of asymptomatic infections and
displayed greater relatedness to isolates from Sumba than to K2, possibly
reflecting imported infections. CONCLUSIONS: The results demonstrate the greater
refractoriness of P. vivax versus P. falciparum to control measures, and risk of
distinct parasite subpopulations persisting in the community undetected by
passive surveillance. These findings highlight the need for complimentary new
surveillance strategies to identify transmission patterns that cannot be detected
with traditional malariometric methods.
PMID- 28498861
TI - Modulation of caveolins, integrins and plasma membrane repair proteins in
anthracycline-induced heart failure in rabbits.
AB - Anthracyclines are chemotherapeutic drugs known to induce heart failure in a dose
dependent manner. Mechanisms involved in anthracycline cardiotoxicity are an area
of relevant investigation. Caveolins bind, organize and regulate receptors and
signaling molecules within cell membranes. Caveolin-3 (Cav-3), integrins and
related membrane repair proteins can function as cardioprotective proteins.
Expression of these proteins in anthracycline-induced heart failure has not been
evaluated. We tested the hypothesis that daunorubicin alters cardioprotective
protein expression in the heart. Rabbits were administered daunorubicin (3 mg/kg,
IV) weekly, for three weeks or nine weeks. Nine weeks but not three weeks of
daunorubicin resulted in progressive reduced left ventricular function. Cav-3
expression in the heart was unchanged at three weeks of daunorubicin and
increased in nine week treated rabbits when compared to control hearts. Electron
microscopy showed caveolae in the heart were increased and mitochondrial number
and size were decreased after nine weeks of daunorubicin. Activated beta-1
(beta1) integrin and the membrane repair protein MG53 were increased after nine
weeks of daunorubicin vs. controls with no change at the three week time point.
The results suggest a potential pathophysiological role for Cav3, integrins and
membrane repair in daunorubicin-induced heart failure.
PMID- 28498862
TI - Severity and duration of diabetic foot ulcer (DFU) before seeking care as
predictors of healing time: A retrospective cohort study.
AB - OBJECTIVES: To investigate whether A) duration of ulcer before start of treatment
in specialist health care, and B) severity of ulcer according to University of
Texas classification system (UT) at start of treatment (baseline), are
independent predictors of healing time. METHODS: This retrospective cohort study,
based on electronic medical record data, included 105 patients from two
outpatient clinics in Western Norway with a new diabetic foot ulcer during 2009
2011. The associations of duration of ulcer and ulcer severity with healing time
were assessed using cumulative incidence curves and subdistribution hazard ratio
estimated using competing risk regression with adjustment for potential
confounders. RESULTS: Of the 105 participants, 45.7% achieved ulcer healing,
36.2% underwent amputations, 9.5% died before ulcer healing and 8.5% were lost to
follow-up. Patients who were referred to specialist health care by a general
practitioner >= 52 days after ulcer onset had a 58% (SHR 0.42, CI 0.18-0.98)
decreased healing rate compared to patients who were referred earlier, in the
adjusted model. High severity (grade 2/3, stage C/D) according to the UT
classification system was associated with a decreased healing rate compared to
low severity (grade1, stage A/B or grade 2, stage A) with SHR (95% CI) equal to
0.14 (0.05-0.43) after adjustment for referral time and other potential
confounders. CONCLUSION: Early detection and referral by both the patient and
general practitioner are crucial for optimal foot ulcer healing. Ulcer grade and
severity are also important predictors for healing time, and early screening to
assess the severity and initiation of prompt treatment is important.
PMID- 28498864
TI - Green material selection for sustainability: A hybrid MCDM approach.
AB - Green material selection is a crucial step for the material industry to
comprehensively improve material properties and promote sustainable development.
However, because of the subjectivity and conflicting evaluation criteria in its
process, green material selection, as a multi-criteria decision making (MCDM)
problem, has been a widespread concern to the relevant experts. Thus, this study
proposes a hybrid MCDM approach that combines decision making and evaluation
laboratory (DEMATEL), analytical network process (ANP), grey relational analysis
(GRA) and technique for order performance by similarity to ideal solution
(TOPSIS) to select the optimal green material for sustainability based on the
product's needs. A nonlinear programming model with constraints was proposed to
obtain the integrated closeness index. Subsequently, an empirical application of
rubbish bins was used to illustrate the proposed method. In addition, a
sensitivity analysis and a comparison with existing methods were employed to
validate the accuracy and stability of the obtained final results. We found that
this method provides a more accurate and effective decision support tool for
alternative evaluation or strategy selection.
PMID- 28498863
TI - Notch ligands regulate the muscle stem-like state ex vivo but are not sufficient
for retaining regenerative capacity.
AB - Myogenic stem cells are a promising avenue for the treatment of muscular
disorders. Freshly isolated muscle stem cells have a remarkable engraftment
ability in vivo, but their cell number is limited. Current conventional culture
conditions do not allow muscle stem cells to expand in vitro with their bona fide
engraftment efficiency, requiring the improvement of culture procedures for
achieving successful cell-therapy for muscle disorders. Here we expanded mouse
muscle stem cells and human myoblasts with Notch ligands, DLL1, DLL4, and JAG1 to
activate Notch signaling in vitro and to investigate whether these cells could
retain their engraftment efficiency. Notch signaling promotes the expansion of
Pax7+MyoD- mouse muscle stem-like cells and inhibits differentiation even after
passage in vitro. Treatment with Notch ligands induced the Notch target genes and
generated PAX7+MYOD- stem-like cells from human myoblasts previously cultured on
conventional culture plates. However, cells treated with Notch ligands exhibit a
stem cell-like state in culture, yet their regenerative ability was less than
that of freshly isolated cells in vivo and was comparable to that of the control.
These unexpected findings suggest that artificial maintenance of Notch signaling
alone is insufficient for improving regenerative capacity of mouse and human
donor-muscle cells and suggest that combinatorial events are critical to achieve
muscle stem cell and myoblast engraftment potential.
PMID- 28498865
TI - When do traumatic experiences alter risk-taking behavior? A machine learning
analysis of reports from refugees.
AB - Exposure to traumatic stressors and subsequent trauma-related mental changes may
alter a person's risk-taking behavior. It is unclear whether this relationship
depends on the specific types of traumatic experiences. Moreover, the association
has never been tested in displaced individuals with substantial levels of
traumatic experiences. The present study assessed risk-taking behavior in 56
displaced individuals by means of the balloon analogue risk task (BART). Exposure
to traumatic events, symptoms of posttraumatic stress disorder and depression
were assessed by means of semi-structured interviews. Using a novel statistical
approach (stochastic gradient boosting machines), we analyzed predictors of risk
taking behavior. Exposure to organized violence was associated with less risk
taking, as indicated by fewer adjusted pumps in the BART, as was the reported
experience of physical abuse and neglect, emotional abuse, and peer violence in
childhood. However, civil traumatic stressors, as well as other events during
childhood were associated with lower risk taking. This suggests that the
association between global risk-taking behavior and exposure to traumatic stress
depends on the particular type of the stressors that have been experienced.
PMID- 28498866
TI - Cognitive adaptation in asexual and sexual wasps living in contrasted
environments.
AB - Differences in learning and memory dynamics between populations are suspected to
result from differences in ecological constraints such as resource distribution.
The two reproductive modes (strains) of the parasitoid wasp Venturia canescens
share the same geographical areas but live in contrasting habitats: arrhenotokous
wasps live in the wild (generally orchards), whereas thelytokous ones live mostly
in stored-products buildings (e.g. granaries). This species thus represents a
relevant biological model for understanding the relationship between the
ecological constraints faced by a species and its memory and learning ability. We
showed that after having laid eggs in presence of both a synthetic odour and
natural olfactory cues of their host, arrhenotokous wasps exhibited a change in
their behavioural response towards the synthetic odour that was at least as
pronounced as in thelytokous ones even though they were faster in their decision
making process. This is consistent with better learning skills in arrhenotokous
wasps. The corresponding memory trace persisted in both strains for at least 51
h. We compare and discuss the learning and memory ablities of both strains as a
function of their costs and benefits in their preferential habitats.
PMID- 28498867
TI - Multilocus genotyping of Enterocytozoon bieneusi derived from nonhuman primates
in southwest China.
AB - Enterocytozoon bieneusi has been increasingly reported in non-human primates
(NHPs) in recent years, and this has garnered attention. However, reports of E.
bieneusi infections in NHPs are limited worldwide. To appreciate the genetic
diversity and assess the zoonotic potential during the transmission of human
microsporidiosis, we examined a total of 369 fecal samples from NHPs and
performed PCR amplification of the ITS gene of E. bieneusi. An infection rate of
12.5% (46/369) was detected in NHPs, with three known genotypes (D, PigEBITS7,
and SC02) and a novel genotype (SCM01) characterized. Phylogenetic analysis
indicated that all four genotypes in our study were classified as zoonotic group
1. Multilocus genotyping of positive E. bieneusi strains revealed that 36, 37,
30, and 29 specimens were successfully amplified and sequenced to generate 16,
six, four, and five types of MS1, MS3, MS4, and MS7 loci, respectively. Twenty
four specimens were successfully amplified and sequenced at all four loci,
forming 13 multilocus genotypes (MLGs). The occurrence of zoonotic genotypes
suggests that zoonotic transmission of E. bieneusi between humans and NHPs has
probably occurred and NHPs could be a source of human microspordiosis.
PMID- 28498868
TI - A Drosophila model for developmental nicotine exposure.
AB - Despite the known health risks of tobacco smoking, many people including pregnant
women continue smoking. The effects of developmental nicotine exposure are known,
but the underlying mechanisms are not well understood. Drosophila melanogaster is
a model organism that can be used for uncovering genetic and molecular mechanisms
for drugs of abuse. Here I show that Drosophila can be a model to elucidate the
mechanisms for nicotine's effects on a developing organism. Drosophila reared on
nicotine food display developmental and behavioral effects similar to those in
mammals including decreased survival and weight, increased developmental time,
and decreased sensitivity to acute nicotine and ethanol. The Drosophila nicotinic
acetylcholine receptor subunit alpha 7 (Dalpha7) mediates some of these effects.
A novel role for Dalpha7 on ethanol sedation in Drosophila is also shown. Future
research taking advantage of the genetic and molecular tools for Drosophila will
allow additional discovery of the mechanisms behind the effects of nicotine
during development.
PMID- 28498869
TI - The effectiveness of modern cardiac rehabilitation: A systematic review of recent
observational studies in non-attenders versus attenders.
AB - BACKGROUND: The beneficial effects of cardiac rehabilitation (CR) have been
challenged in recent years and there is now a need to investigate whether current
CR programmes, delivered in the context of modern cardiology, still benefit
patients. METHODS: A systematic review of non-randomised controlled studies was
conducted. Electronic searches of Medline, Embase, CINAHL, science citation index
(web of science), CIRRIE and Open Grey were undertaken. Non-randomised studies
investigating the effects of CR were included when recruitment occurred from the
year 2000 onwards in accordance with significant CR guidance changes from the
late 1990's. Adult patients diagnosed with acute myocardial infarction (AMI) were
included. Non-English articles were considered. Two reviewers independently
screened articles according to pre-defined selection criteria as reported in the
PROSPERO database (CRD42015024021). RESULTS: Out of 2,656 articles, 8 studies
involving 9,836 AMI patients were included. Studies were conducted in 6
countries. CR was found to reduce the risk of all-cause and cardiac-related
mortality and improve Health-Related Quality of Life (HRQOL) significantly in at
least one domain. The benefits of CR in terms of recurrent MI were inconsistent
and no significant effects were found regarding re-vascularisation or re
hospitalisation following AMI. CONCLUSION: Recent observational evidence draws
different conclusions to the most current reviews of trial data with respect to
total mortality and re-hospitalisation, questioning the representativeness of
historic data in the modern cardiological era. Future work should seek to clarify
which patient and service level factors determine the likelihood of achieving
improved all-cause and cardiac mortality and reduced hospital re-admissions.
PMID- 28498871
TI - Towards implementation of cellular automata in Microbial Fuel Cells.
AB - The Microbial Fuel Cell (MFC) is a bio-electrochemical transducer converting
waste products into electricity using microbial communities. Cellular Automaton
(CA) is a uniform array of finite-state machines that update their states in
discrete time depending on states of their closest neighbors by the same rule.
Arrays of MFCs could, in principle, act as massive-parallel computing devices
with local connectivity between elementary processors. We provide a theoretical
design of such a parallel processor by implementing CA in MFCs. We have chosen
Conway's Game of Life as the 'benchmark' CA because this is the most popular CA
which also exhibits an enormously rich spectrum of patterns. Each cell of the
Game of Life CA is realized using two MFCs. The MFCs are linked electrically and
hydraulically. The model is verified via simulation of an electrical circuit
demonstrating equivalent behaviours. The design is a first step towards future
implementations of fully autonomous biological computing devices with massive
parallelism. The energy independence of such devices counteracts their somewhat
slow transitions-compared to silicon circuitry-between the different states
during computation.
PMID- 28498870
TI - Brg1 chromatin remodeling ATPase balances germ layer patterning by amplifying the
transcriptional burst at midblastula transition.
AB - Zygotic gene expression programs control cell differentiation in vertebrate
development. In Xenopus, these programs are initiated by local induction of
regulatory genes through maternal signaling activities in the wake of zygotic
genome activation (ZGA) at the midblastula transition (MBT). These programs lay
down the vertebrate body plan through gastrulation and neurulation, and are
accompanied by massive changes in chromatin structure, which increasingly
constrain cellular plasticity. Here we report on developmental functions for
Brahma related gene 1 (Brg1), a key component of embyronic SWI/SNF chromatin
remodeling complexes. Carefully controlled, global Brg1 protein depletion in X.
tropicalis and X. laevis causes embryonic lethality or developmental arrest from
gastrulation on. Transcriptome analysis at late blastula, before development
becomes arrested, indicates predominantly a role for Brg1 in transcriptional
activation of a limited set of genes involved in pattern specification processes
and nervous system development. Mosaic analysis by targeted microinjection
defines Brg1 as an essential amplifier of gene expression in dorsal
(BCNE/Nieuwkoop Center) and ventral (BMP/Vent) signaling centers. Moreover, Brg1
is required and sufficient for initiating axial patterning in cooperation with
maternal Wnt signaling. In search for a common denominator of Brg1 impact on
development, we have quantitatively filtered global mRNA fluctuations at MBT. The
results indicate that Brg1 is predominantly required for genes with the highest
burst of transcriptional activity. Since this group contains many key
developmental regulators, we propose Brg1 to be responsible for raising their
expression above threshold levels in preparation for embryonic patterning.
PMID- 28498872
TI - A sequential model for the structure of health care utilization.
AB - Traditional measurement models of health care utilization are not able to
represent the complex structure of health care utilization. In this qualitative
study, we, therefore, developed a new model to represent the health care
utilization structure. In Norway and Germany, we conducted episodic interviews,
participant observation and a concurrent context analysis. Data was analyzed by
thematic coding in the framework of grounded theory. Consultations do very often
not only have one single reason for encounter. They are usually not independent
events but form part of consultation sequences. We could find structural
differences between Norway and Germany regarding the flow of information between
consultations and which providers are involved in health care in what way. This
leads to a sequential model, in which health care utilization is seen as
sequences of consultations. Such health care utilization sequences consist of
nodes which are connected by edges. Nodes represent patient-provider contacts and
edges depict the flow of information. Time and the level of health care providers
are dimensions in the model. These sequences can be described by different
measures and aggregated on population level. Thus, the sequential model can be
further used in analyzing health care utilization quantitatively, e.g., by using
routine data.
PMID- 28498873
TI - Associations of androgens with depressive symptoms and cognitive status in the
general population.
AB - OBJECTIVES: Associations between androgens and depressive symptoms were mostly
reported from cross-sectional and patient-based studies. STUDY DESIGN/MAIN
OUTCOME MEASURES: Longitudinal data from 4,110 participants of the Study of
Health in Pomerania were used to assess sex-specific associations of baseline
total and free testosterone, androstenedione and sex hormone-binding globulin
with incident depressive symptoms and cognitive status at 5- and 10-year follow
up. RESULTS: Despite sex-specific differences in depressive symptoms prevalence
at baseline (women: 17.4%, men: 8.1%), cross-sectional analyses showed no
associations between sex hormones and depressive symptoms. In age-adjusted
longitudinal analyses, total testosterone was associated with incident depressive
symptoms (relative risk at 5-year follow-up: 0.73, 95% confidence interval: 0.58
0.92). Similarly, age-adjusted analyses showed a positive association between sex
hormone-binding globulin and cognitive status in men (beta-coefficient per
standard deviation: 0.44, 95% confidence interval: 0.13-0.74). In women, age
adjusted associations of androstenedione with baseline depressive symptoms
(relative risk: 0.88, 95% confidence interval: 0.77-0.99) were found. None of the
observed associations remained after multivariable adjustment. CONCLUSIONS: The
present population-based, longitudinal study revealed inverse associations
between sex hormones and depressive symptoms. However, the null finding after
multivariable adjustment suggests, that the observed associations were not
independent of relevant confounders including body mass index, smoking and
physical inactivity. Furthermore, the low number of incident endpoints in our non
clinical population-based sample limited the statistical power and reduced the
chance to detect a statistically significant effect.
PMID- 28498875
TI - Predictive models of poly(ethylene-terephthalate) film degradation under multi
factor accelerated weathering exposures.
AB - Accelerated weathering exposures were performed on poly(ethylene-terephthalate)
(PET) films. Longitudinal multi-level predictive models as a function of PET
grades and exposure types were developed for the change in yellowness index (YI)
and haze (%). Exposures with similar change in YI were modeled using a linear
fixed-effects modeling approach. Due to the complex nature of haze formation,
measurement uncertainty, and the differences in the samples' responses, the
change in haze (%) depended on individual samples' responses and a linear mixed
effects modeling approach was used. When compared to fixed-effects models, the
addition of random effects in the haze formation models significantly increased
the variance explained. For both modeling approaches, diagnostic plots confirmed
independence and homogeneity with normally distributed residual errors.
Predictive R2 values for true prediction error and predictive power of the models
demonstrated that the models were not subject to over-fitting. These models
enable prediction under pre-defined exposure conditions for a given exposure time
(or photo-dosage in case of UV light exposure). PET degradation under cyclic
exposures combining UV light and condensing humidity is caused by photolytic and
hydrolytic mechanisms causing yellowing and haze formation. Quantitative
knowledge of these degradation pathways enable cross-correlation of these lab
based exposures with real-world conditions for service life prediction.
PMID- 28498874
TI - Soluble bone-derived osteopontin promotes migration and stem-like behavior of
breast cancer cells.
AB - Breast cancer is a leading cause of cancer death in women, with the majority of
these deaths caused by metastasis to distant organs. The most common site of
breast cancer metastasis is the bone, which has been shown to provide a rich
microenvironment that supports the migration and growth of breast cancer cells.
Additionally, growing evidence suggests that breast cancer cells that do
successfully metastasize have a stem-like phenotype including high activity of
aldehyde dehydrogenase (ALDH) and/or a CD44+CD24- phenotype. In the current
study, we tested the hypothesis that these ALDHhiCD44+CD24- breast cancer cells
interact with factors in the bone secondary organ microenvironment to facilitate
metastasis. Specifically, we focused on bone-derived osteopontin and its ability
to promote the migration and stem-like phenotype of breast cancer cells. Our
results indicate that bone-derived osteopontin promotes the migration,
tumorsphere-forming ability and colony-forming ability of whole population and
ALDHhiCD44+CD24- breast cancer cells in bone marrow-conditioned media (an ex vivo
representation of the bone microenvironment) (p<=0.05). We also demonstrate that
CD44 and RGD-dependent cell surface integrins facilitate this functional response
to bone-derived osteopontin (p<=0.05), potentially through activation of WNK-1
and PRAS40-related pathways. Our findings suggest that soluble bone-derived
osteopontin enhances the ability of breast cancer cells to migrate to the bone
and maintain a stem-like phenotype within the bone microenvironment, and this may
contribute to the establishment and growth of bone metastases.
PMID- 28498876
TI - Trace element and metal sequestration in vitellaria and sclerites, and reactive
oxygen intermediates in a freshwater monogenean, Paradiplozoon ichthyoxanthon.
AB - Exposure to metals and other trace elements negatively affects infection dynamics
of monogeneans, including diplozoids, but, physiological mechanisms linked to
exposure have yet to be documented. In this study sequestration of trace elements
and reactive oxygen intermediate production in the monogenean, Paradiplozoon
ichthyoxanthon, was demonstrated. During dissection of host fish, Labeobarbus
aeneus, the gills were excised and assessed for P. ichthyoxanthon, which were
removed and frozen for fluorescence microscopy or fixed for transmission electron
microscopy. Trace elements were sequestered in the vitellaria and sclerites in P.
ichthyoxanthon, and the presence of reactive oxygen intermediates was observed
predominantly in the tegument of the parasite. Trace elements and metals
identified and ranked according to weight percentages (wt%) in the vitellaria
were Cu > C > Au > O > Cr > Fe > Si while for the sclerites C > Cu > O > Au > Fe
> Cr > Si were identified. For most element detected, readings were higher in the
vitellaria than the sclerites, except for C and O which were higher in sclerites.
Specifically for metals, all levels detected in the vitellaria were greater than
in sclerites. Based on the proportion of trace elements present in the vitellaria
and sclerites it appears that most trace elements including metals were
sequestered in the vitellaria. The results of reactive oxygen intermediate
production in the tegument of the parasite suggests either trace element
accumulation takes place across the tegument or results from the action of the
host's immune response on the parasite. The results serve as the first
demonstration of trace element sequestration and reactive oxygen intermediates in
a freshwater monogenean parasite.
PMID- 28498877
TI - High end of life health care costs and hospitalization burden in inflammatory
bowel disease patients: A population-based study.
AB - BACKGROUND: End of life (EOL) care is associated with greater costs, particularly
for acute care services. In patients with inflammatory bowel disease (IBD), EOL
costs may be accentuated due to reliance on hospital-based services and expensive
diagnostic tests and treatments. We aimed to compare EOL health care use and
costs between IBD and non-IBD decedents. METHODS: We conducted a retrospective
cohort study of all decedents of Ontario, Canada between 2010 and 2013 using
linked health administrative data. IBD (N = 2,214) and non-IBD (N = 262,540)
decedents were compared on total direct health care costs in the last year of
life and hospitalization time during the last 90 days of life. RESULTS: During
the last 90 days of life, IBD patients spent an average of 16 days in hospital,
equal to 2.1 greater adjusted hospital days (95% confidence interval [CI] 1.5-2.8
days) than non-IBD patients. IBD diagnosis was associated with $7,210 CAD (95% CI
$5,005 - $9,464) higher adjusted per-patient cost in the last year of life, of
which 76% was due to excess hospitalization costs. EOL cost of IBD care was
higher than 15 of 16 studied chronic conditions. Health care costs rose sharply
in the last 90 days of life, primarily due to escalating hospitalization costs.
CONCLUSIONS: IBD patients spend more time in hospital and incur substantially
greater health care costs than other decedents as they approach the EOL. These
excess costs could be curtailed through avoidance of unnecessary hospitalizations
and expensive treatments in the setting of irreversible deterioration.
PMID- 28498879
TI - Nonsurgical Medical Penile Girth Augmentation: Experience-Based Recommendations.
AB - Penile augmentation is increasingly sought by men who are dissatisfied with the
size and/or appearance of their penis. However, augmentation procedures are still
considered to be highly controversial with no standardized recommendations
reported in the medical literature and limited outcome data. Nevertheless, these
procedures continue to be performed in increasing numbers in private settings.
Therefore, there is a need for safe, effective, and minimally invasive procedures
to be developed, evaluated, and reported in the research literature. In this
article, we focus particularly on girth enhancement procedures rather than
lengthening procedures as penile girth appears to be particularly important for
sexual satisfaction. We discuss the advantages and disadvantages of the common
techniques to date, with a focus on the minimally invasive injectable girth
augmentation techniques. Based on considerable operative experience, we offer our
own suggestions for patient screening, technique selection, and perioperative
care.
PMID- 28498878
TI - The malleable gut microbiome of juvenile rainbow trout (Oncorhynchus mykiss):
Diet-dependent shifts of bacterial community structures.
AB - Plant-derived protein sources are the most relevant substitutes for fishmeal in
aquafeeds. Nevertheless, the effects of plant based diets on the intestinal
microbiome especially of juvenile Rainbow trout (Oncorhynchus mykiss) are yet to
be fully investigated. The present study demonstrates, based on 16S rDNA
bacterial community profiling, that the intestinal microbiome of juvenile Rainbow
trout is strongly affected by dietary plant protein inclusion levels. After first
feeding of juveniles with either 0%, 50% or 97% of total dietary protein content
derived from plants, statistically significant differences of the bacterial gut
community for the three diet-types were detected, both at phylum and order level.
The microbiome of juvenile fish consisted mainly of the phyla Proteobacteria,
Firmicutes, Bacteroidetes, Fusobacteria and Actinobacteria, and thus fits the
salmonid core microbiome suggested in previous studies. Dietary plant proteins
significantly enhanced the relative abundance of the orders Lactobacillales,
Bacillales and Pseudomonadales. Animal proteins in contrast significantly
promoted Bacteroidales, Clostridiales, Vibrionales, Fusobacteriales and
Alteromonadales. The overall alpha diversity significantly decreased with
increasing plant protein inclusion levels and with age of experimental animals.
In order to investigate permanent effects of the first feeding diet-type on the
early development of the microbiome, a diet change was included in the study
after 54 days, but no such effects could be detected. Instead, the microbiome of
juvenile trout fry was highly dependent on the actual diet fed at the time of
sampling.
PMID- 28498880
TI - A two-arm multicenter phase II trial of one cycle chemoselection split-dose
docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy before two
cycles of split TPF followed by curative surgery combined with postoperative
radiotherapy in patients with locally advanced oral and oropharyngeal squamous
cell cancer (TISOC-1).
AB - Background: Induction chemotherapy (ICT) with docetaxel, cisplatin and
fluorouracil (TPF) followed by radiotherapy is an effective treatment option for
locally advanced head and neck cancer. This phase II study investigated the
effectivity of a split-dose TPF ICT before surgery for locally advanced
resectable (stage III/IVA) oral and oropharyngeal cancer. Patients and methods:
Patients received TPF split on two dosages on days 1 and 8 per cycle (30 mg/m2
docetaxel, 40 mg/m2 cisplatin, 2000 mg/m2 fluorouracil per week). Responders
(reduction tumor volume >=30% after first cycle) received three 3-week cycles and
non-responders only one cycle before surgery and postoperative
radio(chemo)therapy (RCT). The primary endpoint was progression-free survival
rate after 24 months. Secondary endpoints were amongst others overall survival,
histopathological response to ICT, toxicity, quality of life and swallowing
function. Results: Fifty-four patients (91% stage IVA, 87% male, 72%
oropharyngeal cancer, 70% responders) were eligible for a per-protocol analysis.
The progression-free survival rate after 24 months was 88.5% for responders and
60.6% for non-responders (P = 0.005). The overall survival rate after 24 months
was 97.3% for responders and 73.7% for non-responders (P = 0.032). The rate of
histopathological complete remission of the primary tumor was higher in
responders (P = 0.015). High-risk classification for postoperative RCT was lower
in responders (P < 0.0001). The most common grade 3+ adverse event was
neutropenia in 26% of patients during ICT and mucositis in 13% during
postoperative RCT. During treatment and follow-up quality of life and swallowing
function was not different between responders and non-responders. Conclusion:
Patients with oral and oropharyngeal cancer responding to split-dose TPF before
surgery and postoperative RCT show good oncological results. The tri-modal
treatment regime was well tolerated. ICT using tumor response as criterion for
duration of ICT before surgery of oral and oropharyngeal cancer merits additional
investigation in a phase III study. Clinical trial number: NCT01108042.
PMID- 28498881
TI - Can p40 (Polyclonal) Replace p63 (Clone 4A4) in the Cytologic Diagnosis of
Pulmonary Non-Small Cell Carcinoma?
AB - Objectives: Differentiating squamous cell carcinoma from adenocarcinoma (ACA) in
cytology specimens can be challenging. Recent literature showed p40 had higher
specificity than p63 for this purpose. Methods: We identified 190 cytology cases
with p40 (polyclonal) and p63 (monoclonal clone 4A4) immunohistochemistry,
including specimens from fine-needle aspirations (FNAs) and effusions. Results:
ACAs of lung origin stained for p40 and p63 in 21% and 20% of cases,
respectively, regardless of specimen site. Among lung FNAs of primary pulmonary
ACAs (n = 42), 14% were positive for p40 and 24% were positive for p63. Of the 20
pulmonary ACAs in effusions, more cases showed p40 positivity (40%) compared with
FNAs, whereas p63 were positive in 15%. Among metastatic ACAs from other sites (n
= 14), more cases were positive for p40 than p63. Conclusions: Polyclonal p40
yields a level of false positivity in ACAs similar to p63, which is highest in
effusions and is not limited to lung origin.
PMID- 28498882
TI - Mutational signatures and mutable motifs in cancer genomes.
AB - Cancer is a genetic disorder, meaning that a plethora of different mutations,
whether somatic or germ line, underlie the etiology of the 'Emperor of Maladies'.
Point mutations, chromosomal rearrangements and copy number changes, whether they
have occurred spontaneously in predisposed individuals or have been induced by
intrinsic or extrinsic (environmental) mutagens, lead to the activation of
oncogenes and inactivation of tumor suppressor genes, thereby promoting
malignancy. This scenario has now been recognized and experimentally confirmed in
a wide range of different contexts. Over the past decade, a surge in available
sequencing technologies has allowed the sequencing of whole genomes from liquid
malignancies and solid tumors belonging to different types and stages of cancer,
giving birth to the new field of cancer genomics. One of the most striking
discoveries has been that cancer genomes are highly enriched with mutations of
specific kinds. It has been suggested that these mutations can be classified into
'families' based on their mutational signatures. A mutational signature may be
regarded as a type of base substitution (e.g. C:G to T:A) within a particular
context of neighboring nucleotide sequence (the bases upstream and/or downstream
of the mutation). These mutational signatures, supplemented by mutable motifs (a
wider mutational context), promise to help us to understand the nature of the
mutational processes that operate during tumor evolution because they represent
the footprints of interactions between DNA, mutagens and the enzymes of the
repair/replication/modification pathways.
PMID- 28498884
TI - Global patient outcomes after elective surgery: prospective cohort study in 27
low-, middle- and high-income countries.
PMID- 28498883
TI - Prognostic Significance of Spot Urine Na/K for Longitudinal Changes in Blood
Pressure and Renal Function: The Nagahama Study.
AB - BACKGROUND: Urinary sodium-to-potassium ratio (Na/K) represents a simple measure
of sodium load and has been reported to be associated with blood pressure (BP)
levels in a cross-sectional setting even with spot measurements. The aim of the
present large-scale cohort study is to determine prognostic significance of spot
urine Na/K for longitudinal changes in BP levels and renal function. METHODS: The
present study population consisted of 7,063 individuals from the general
population. Clinical parameters were measured at baseline and at a follow-up
interval of 5 years. RESULTS: Mean systolic BP was slightly increased during the
follow-up period (overall, 124 +/- 17 to 125 +/- 18 mm Hg; nontreated
participants, 119 +/- 15 to 122 +/- 17 mm Hg). Although, the urinary Na/K
demonstrated a linear association with BP in a cross-sectional analysis (P <
0.001), analysis of repeated measured BP values identified baseline Na/K * time
interaction, i.e., an intraindividual effect, as an inverse determinant (F =
76.9, P < 0.001) independently of hypertension status and fasting conditions
possibly due to regression to the mean of temporary high baseline Na/K values at
baseline. Spot urine Na/K values were found to be positively associated with
renal function in a cross-sectional analysis (P < 0.001). Although baseline Na/K
* time interaction showed inverse associated with renal functional decline (F =
85.8, P < 0.001), this inverse association might not represent physiological
relationship in likewise fashion with the analysis for BP. CONCLUSIONS: Spot
urine Na/K may have limited utility as a prognostic marker of longitudinal BP
change, as well as renal functional decline.
PMID- 28498885
TI - PROXiMATE: a database of mutant protein-protein complex thermodynamics and
kinetics.
AB - Summary: We have developed PROXiMATE, a database of thermodynamic data for more
than 6000 missense mutations in 174 heterodimeric protein-protein complexes,
supplemented with interaction network data from STRING database, solvent
accessibility, sequence, structural and functional information, experimental
conditions and literature information. Additional features include complex
structure visualization, search and display options, download options and a
provision for users to upload their data. Availability and implementation: The
database is freely available at http://www.iitm.ac.in/bioinfo/PROXiMATE/ . The
website is implemented in Python, and supports recent versions of major browsers
such as IE10, Firefox, Chrome and Opera. Contact: gromiha@iitm.ac.in.
Supplementary information: Supplementary data are available at Bioinformatics
online.
PMID- 28498886
TI - Risky Drinkers Underestimate their Own Alcohol Consumption.
PMID- 28498887
TI - Sex Differences in Risk for Alzheimer's Disease Related to Neurotrophin Gene
Polymorphisms: The Cache County Memory Study.
AB - Neurotrophins, including nerve-growth factor and brain-derived neurotrophic
factor, have been implicated in Alzheimer's disease (AD). Associations between AD
and neurotrophin signaling genes have been inconsistent, with few studies
examining sex differences in risk. We examined four single-nucleotide
polymorphisms (SNPs) involved in neurotrophin signaling (rs6265, rs56164415,
rs2289656, rs2072446) and risk for AD by sex in a population-based sample of
older adults. Three thousand four hundred and ninety-nine individuals without
dementia at baseline [mean (standard deviation) age = 74.64 (6.84), 58% female]
underwent dementia screening and assessment over four triennial waves. Cox
regression was used to examine time to AD or right censoring for each SNP. Female
carriers of the minor T allele for rs2072446 and rs56164415 had a 60% (hazard
ratio [HR] = 1.60, 95% confidence interval [CI] = 1.02-2.51) and 93% (HR = 1.93,
95% CI = 1.30-2.84) higher hazard for AD, respectively, than male noncarriers of
the T allele. Furthermore, male carriers of the T allele of rs2072446 had a 61%
lower hazard (HR = 0.39, 95% CI = 0.14-1.06) than male noncarriers at trend-level
significance (p = .07). The association between certain neurotrophin gene
polymorphisms and AD differs by sex and may explain inconsistent findings in the
literature.
PMID- 28498889
TI - UK anaesthetists' perspectives and experiences of severe perioperative
anaphylaxis: NAP6 baseline survey.
AB - Background: There is limited information on UK anaesthetists' perspectives and
experiences of perioperative anaphylaxis. This baseline survey of the Sixth
National Audit Project (NAP6) aimed to identify relevant departmental
preparedness and practices, and individual experiences, perceptions and drug
avoidance patterns. Methods: All anaesthetists in 356 UK NHS hospitals were
invited to complete an electronic survey. Results: 11 104 anaesthetists (77%
crude response rate) from 341 (96%) hospitals responded. Most had immediate
access to guidelines for anaphylaxis treatment (87%) and established referral
pathways for investigation (82%), but a minority reported access to designated
treatment packs (37%) or an anaphylaxis lead (35%). Anaesthetists reported 1734
cases of suspected perioperative anaphylaxis in 2014-5 of which 81% were referred
for specialist investigation and 14% reported to the Medicines and Healthcare
Products Regulatory Agency (MHRA). In their career, 76% of respondents had seen a
case of perioperative anaphylaxis (1:7.25 years of practice) and 4% reported a
death (1:311 years of practice), equivalent to 2.3% of events being fatal. Agents
most frequently perceived to cause anaphylaxis were antibiotics, particularly
penicillins, and neuromuscular blocking agents, notably rocuronium. Suxamethonium
and penicillins were avoided by a higher proportion of respondents than events
attributed to these drugs whereas the converse was true for atracurium and
teicoplanin. Conclusions: This is the largest ever survey of anaesthetists'
practices and experiences relating to perioperative anaphylaxis. It identifies
gaps in preparedness and referral for further investigation and to the UK MHRA.
It provides important data about drugs implicated in such events and
anaesthetists' attitudes to anaphylaxis.
PMID- 28498888
TI - Cardiomyocyte-specific loss of mitochondrial p32/C1qbp causes cardiomyopathy and
activates stress responses.
AB - Aims: Mitochondria are important organelles, dedicated to energy production.
Mitochondrial p32/C1qbp, which functions as an RNA and protein chaperone,
interacts with mitochondrial mRNA and is indispensable for mitochondrial function
through its regulation of mitochondrial translation in cultured cell lines.
However, the precise role of p32/C1qbp in vivo is poorly understood because of
embryonic lethality in the systemic p32-deficient mouse. The goal of this study
was to examine the physiological function of mitochondrial p32/C1qbp in the
heart. Methods and results: We investigated the role of p32 in regulating cardiac
function in mice using a Cre-loxP recombinase technology against p32 with
tamoxifen-inducible knockdown or genetic ablation during postnatal periods.
Cardiomyocyte-specific deletion of p32 resulted in contractile dysfunction,
cardiac dilatation and cardiac fibrosis, compared with hearts of control mice. We
also found decreased COX1 expression, decreased rates of oxygen consumption and
increased oxidative stress, indicating that these mice had cardiac mitochondrial
dysfunction provoked by p32-deficiency at early stage. Next, we investigated
lifespan in cardiac-specific p32-deficient mice. The mice died beginning at 12
months and their median lifespan was ~14 months. Cardiac mitochondria in the p32
deficient mice showed disordered alignment, enlargement and abnormalities in
their internal structure by electron microscopy. We observed that, in p32
deficient compared with control myocytes, AMPKalpha was constitutively
phosphorylated and 4EBP-1 and ribosomal S6K were less phosphorylated, suggesting
impairment of mammalian target of rapamycin signalling. Finally, we found that
expression levels of mitokines such as FGF21 and of integrated stress response
genes were significantly increased. Metabolic analysis demonstrated that the urea
cycle was impaired in the p32-deficient hearts. Conclusion: These findings
support a key role for mitochondrial p32 protein in cardiac myocytes modulating
mitochondrial translation and function, and thereby survival.
PMID- 28498890
TI - Semen Quality as a Predictor of Subsequent Morbidity: A Danish Cohort Study of
4,712 Men With Long-Term Follow-up.
AB - Semen quality has been suggested to be a biological marker of long-term morbidity
and mortality; however, few studies have been conducted on this subject. We
identified 5,370 men seen for infertility at Frederiksberg Hospital, Denmark,
during 1977-2010, and 4,712 of these men were followed in the Danish National
Patient Registry until first hospitalization, death, or the end of the study. We
classified patients according to hospitalizations and the presence of
cardiovascular disease, diabetes, testicular cancer, or prostate cancer. We found
a clear association between sperm concentration below 15 million/mL and all-cause
hospitalizations (hazard ratio = 1.5, 95% confidence interval: 1.4, 1.6) and
cardiovascular disease (hazard ratio = 1.4, 95% confidence interval: 1.2, 1.6),
compared with men with a concentration above 40 million/mL. The probabilities for
hospitalizations were also higher with a low total sperm count and low motility.
Men with a sperm concentration of 195-200 million/mL were, on average,
hospitalized for the first time 7 years later than were men with a sperm
concentration of 0-5 million/mL. Semen quality was associated with long-term
morbidity, and a significantly higher risk of hospitalization was found, in
particular for cardiovascular diseases and diabetes mellitus. Our study supports
the suggestion that semen quality is a strong biomarker of general health.
PMID- 28498891
TI - Adipose tissue depots and inflammation: effects on plasticity and resident
mesenchymal stem cell function.
AB - Adipose tissue (AT) is a highly heterogeneous organ. Beside the heterogeneity
associated to different tissue types (white, brown, and 'brite') and its location
related heterogeneity (subcutaneous, visceral, epicardial, and perivascular,
etc.), AT composition, structure, and functionality are highly dependent on
individual-associated factors. As such, the pro-inflammatory state associated to
the presence of obesity and other cardiovascular risk factors (CVRFs) directly
affects AT metabolism. Furthermore, the adipose-derived stem cells (ASCs) that
reside in the stromal vascular fraction of AT, besides being responsible for most
of the plasticity attributed to AT, is an additional source of heterogeneity.
Thus, ASCs directly contribute to AT homeostasis, cell renewal, and spontaneous
repair. These ASCs share many properties with the bone-marrow mesenchymal stem
cells (i.e. potential to differentiate towards multiple tissue lineages, and
angiogenic, antiapoptotic, and immunomodulatory properties). Moreover, ASCs show
clear advantages in terms of accessibility and quantity of available sample,
their easy in vitro expansion, and the possibility of having an autologous
source. All these properties point out towards a potential use of ASCs in
regenerative medicine. However, the presence of obesity and other CVRFs induces a
pro-inflammatory state that directly impacts ASCs proliferation and
differentiation capacities affecting their regenerative abilities. The focus of
this review is to summarize how inflammation affects the different AT depots and
the mechanisms by which these changes further enhance the obesity-associated
metabolic disturbances. Furthermore, we highlight the impact of obesity-induced
inflammation on ASCs properties and how those effects impair their plasticity.
PMID- 28498892
TI - Incident AIDS or Death After Initiation of Human Immunodeficiency Virus Treatment
Regimens Including Raltegravir or Efavirenz Among Adults in the United States.
AB - Background.: The long-term effectiveness of human immunodeficiency virus (HIV)
treatments containing integrase inhibitors is unknown. Methods.: We use
observational data from the Centers for AIDS Research Network of Integrated
Clinical Systems and the Centers for Disease Control and Prevention to estimate 4
year risk of AIDS and all-cause mortality among 415 patients starting a
raltegravir regimen compared to 2646 starting an efavirenz regimen (both regimens
include emtricitabine and tenofovir disoproxil fumarate). We account for
confounding and selection bias as well as generalizability by standardization for
measured variables, and present both observational intent-to-treat and per
protocol estimates. Results.: At treatment initiation, 12% of patients were
female, 36% black, 13% Hispanic; median age was 37 years, CD4 count 321 cells/uL,
and viral load 4.5 log10 copies/mL. Two hundred thirty-five patients incurred an
AIDS-defining illness or died, and 741 patients left follow-up. After accounting
for measured differences, the 4-year risk was similar among those starting both
regimens (ie, intent-to treat hazard ratio [HR], 0.96 [95% confidence interval
{CI}, .63-1.45]; risk difference, -0.9 [95% CI, -4.5 to 2.7]), as well as among
those remaining on regimens (ie, per-protocol HR, 0.95 [95% CI, .59-1.54]; risk
difference, -0.5 [95% CI, -3.8 to 2.9]). Conclusions.: Raltegravir and efavirenz
based initial antiretroviral therapy have similar 4-year clinical effects.
Vigilance regarding longer-term comparative effectiveness of HIV regimens using
observational data is needed because large-scale experimental data are not
forthcoming.
PMID- 28498893
TI - Role of DHX33 in c-Myc-induced cancers.
AB - Oncogene c-Myc is frequently amplified and activated in human cancers.
Deregulation of c-Myc protein has been shown to occur in 30% of all human
cancers, especially in hematopoietic malignancies. As a transcription factor, c
Myc has been shown to regulate up to 15% of all human genome genes, controlling
diverse cellular activities including cell cycle, ribosome biogenesis, protein
synthesis, metabolism, apoptosis and angiogenesis. In this report, we provide
evidence that the RNA helicase DHX33 is a critical downstream target of c-Myc.
Myc binds to DHX33 upstream promoter region and stimulates its transcription.
Elevated DHX33 protein is pivotal for c-Myc to drive tumor formation. Knockdown
of DHX33 to basal levels in c-Myc overexpressing cells significantly reduced cell
proliferation, cell migration and anchorage-independent cell growth in vitro and
in vivo. Additionally, we found that DHX33 promotes MMP9, MMP14 and urokinase
type plasminogen activator (PLAU) transcription by directly binding to their
promoters, thus promoting cancer cell migration. DHX33 protein was overexpressed
in a certain subset of human non-Hodgkin's lymphoma tissues. Finally, knockdown
of DHX33 significantly inhibits the development of Myc-induced acute myeloid
leukemia. Overall, our results implicate the important role for DHX33 in Myc
induced cancer and point toward its potential therapeutic value in Myc driven
cancers.
PMID- 28498895
TI - Acute Illness Among Surfers After Exposure to Seawater in Dry- and Wet-Weather
Conditions.
AB - Rainstorms increase levels of fecal indicator bacteria in urban coastal waters,
but it is unknown whether exposure to seawater after rainstorms increases rates
of acute illness. Our objective was to provide the first estimates of rates of
acute illness after seawater exposure during both dry- and wet-weather periods
and to determine the relationship between levels of indicator bacteria and
illness among surfers, a population with a high potential for exposure after
rain. We enrolled 654 surfers in San Diego, California, and followed them
longitudinally during the 2013-2014 and 2014-2015 winters (33,377 days of
observation, 10,081 surf sessions). We measured daily surf activities and illness
symptoms (gastrointestinal illness, sinus infections, ear infections, infected
wounds). Compared with no exposure, exposure to seawater during dry weather
increased incidence rates of all outcomes (e.g., for earache or infection,
adjusted incidence rate ratio (IRR) = 1.86, 95% confidence interval (CI): 1.27,
2.71; for infected wounds, IRR = 3.04, 95% CI: 1.54, 5.98); exposure during wet
weather further increased rates (e.g., for earache or infection, IRR = 3.28, 95%
CI: 1.95, 5.51; for infected wounds, IRR = 4.96, 95% CI: 2.18, 11.29). Fecal
indicator bacteria measured in seawater (Enterococcus species, fecal coliforms,
total coliforms) were strongly associated with incident illness only during wet
weather. Urban coastal seawater exposure increases the incidence rates of many
acute illnesses among surfers, with higher incidence rates after rainstorms.
PMID- 28498896
TI - Inhibition of PRDM14 expression in pancreatic cancer suppresses cancer stem-like
properties and liver metastasis in mice.
AB - Pancreatic cancer is one of the most lethal types of cancer, with aggressive
properties characterized by metastasis, recurrence and drug resistance. Cancer
stem cells are considered to be responsible for these properties. PRDM14, a
transcriptional regulator that maintains pluripotency in embryonic stem cells, is
overexpressed in some cancers. Here, we assessed PRDM14 expression and the
effects of PRDM14 knockdown on cancer stem-like phenotypes in pancreatic cancer.
We observed that PRDM14 protein was overexpressed in pancreatic cancer tissues
compared with normal pancreatic tissues. Using lentiviral shRNA-transduced
pancreatic cancer cells, we found that PRDM14 knockdown decreased sphere
formation, number of side population and cell surface marker-positive cells and
subcutaneous xenograft tumors and liver metastasis in mice. This was accompanied
by upregulation of some microRNAs (miRNAs), including miR-125a-3p. miR-125a-3p, a
tumor suppressor that is down-regulated in pancreatic cancer, has been suggested
to regulate the expression of the Src-family kinase, Fyn. In PRDM14-knockdown
cells, Fyn was expressed at lower levels and downstream proteins were less
activated. These changes were considered to cause suppression of the above cancer
phenotypes. In addition, we used small interfering RNA (siRNA)-based therapy
targeting PRDM14 in a mouse model of liver metastasis induced using MIA-PaCa2
cells, and this treatment significantly decreased metastasis and in vitro
migration. Taken together, these results suggest that targeting the
overexpression of PRDM14 suppresses cancer stem-like phenotypes, including liver
metastasis, via miRNA regulation and siRNA-based therapy targeting it shows
promise as a treatment for patients with pancreatic cancer.
PMID- 28498894
TI - The Intersection of Aging Biology and the Pathobiology of Lung Diseases: A Joint
NHLBI/NIA Workshop.
AB - Death from chronic lung disease is increasing and chronic obstructive pulmonary
disease has become the third leading cause of death in the United States in the
past decade. Both chronic and acute lung diseases disproportionately affect
elderly individuals, making it likely that these diseases will become more
frequent and severe as the worldwide population ages. Chronic lung diseases are
associated with substantial morbidity, frequently resulting in exercise limiting
dyspnea, immobilization, and isolation. Therefore, effective strategies to
prevent or treat lung disease are likely to increase healthspan as well as life
span. This review summarizes the findings of a joint workshop sponsored by the
NIA and NHLBI that brought together investigators focused on aging and lung
biology. These investigators encouraged the use of genetic systems and aged
animals in the study of lung disease and the development of integrative systems
based platforms that can dynamically incorporate data sets that describe the
genomics, transcriptomics, epigenomics, metabolomics, and proteomics of the aging
lung in health and disease. Further research was recommended to integrate
benchmark biological hallmarks of aging in the lung with the pathobiology of
acute and chronic lung diseases with divergent pathologies for which advanced age
is the most important risk factor.
PMID- 28498897
TI - Which technique of cusp repair is durable in reimplantation procedure?
AB - OBJECTIVES: We aimed to ascertain the durability of cusp repair techniques used
in reimplantation procedures. METHODS: Between 2000 and 2015, 249 patients (mean
age, 49 +/- 17 years) with aortic insufficiency underwent the reimplantation
procedure. The pathology was acute aortic dissection in 24 and non-dissection in
225 patients. Preoperative aortic regurgitation (AR) was absent in 9, 1+ in 19,
2+ in 20, 3+ in 71 and 4+ in 120 patients. The mean aortic root and ascending
aortic diameters were 47 +/- 9 mm and 38 +/- 7 mm, respectively. The following
techniques of cusp repair were used: none (83), central plication (130), free
margin reinforcement (57) and patch repair (19). Annual echocardiography was
performed. Freedom from moderate aortic insufficiency and aortic valve
reoperation were calculated by the Kaplan-Meier method. Factors influencing the
freedom from moderate or severe AR were calculated by proportional hazard
analysis. RESULTS: Mean follow-up period was 56 +/- 44 months. Freedom from
moderate or severe AR was 82%+/-3% and 77% +/- 4% at 5 and 8 years, respectively,
whereas freedom from aortic valve reoperation was 93%+/-8% and 87% +/- 3% at 5
and 8 years, respectively. Recurrent AR and infection were causes of reoperation
in 13 and 3 patients, respectively. Preoperative cusp prolapse, technique of free
margin reinforcement used and patch repair were significant factors for recurrent
AR by proportional hazard analysis. Central plication was not a significant
factor for recurrent AR. CONCLUSIONS: Preoperative cusp prolapse was a risk
factor, whereas central plication was not a risk factor for recurrent AR. Free
margin reinforcement had a positive effect, whereas patch repair had a negative
effect on aortic valve durability.
PMID- 28498898
TI - Spatial Asymmetry and Short-Term Suppression Underlie Direction Selectivity of
Synaptic Excitation in the Mouse Visual Cortex.
AB - Direction selectivity (DS) of neuronal responses is fundamental for motion
detection. With in vivo whole-cell voltage-clamp recordings from layer (L)4
neurons in the mouse visual cortex, we observed a strong correlation between DS
and spatial asymmetry in the distribution of excitatory input strengths. This
raises an interesting possibility that the latter may contribute to DS. The
preferred direction of excitatory input was found from the stronger to weaker
side of its spatial receptive field. A simple linear summation of asymmetrically
distributed excitatory responses to stationary flash stimuli however failed to
predict the correct directionality: it at best resulted in weak DS with preferred
direction opposite to what was observed experimentally. Further studies with
sequential 2 flash-bar stimulation revealed a short-term suppression of
excitatory input evoked by the late bar. More importantly, the level of the
suppression positively correlated with the relative amplitude of the early-bar
response. Implementing this amplitude-dependent suppressive interaction can
successfully predict DS of excitatory input. Our results suggest that via
nonlinear temporal interactions, the spatial asymmetry can be transformed into
differential temporal integration of inputs under opposite directional movements.
This mechanism may contribute to the DS of excitatory inputs to L4 neurons.
PMID- 28498900
TI - Mid- to long-term results following aortic valve replacement using the Mitroflow
xeno-pericardial bioprosthesis: somewhat different views from 2 high-volume
institutions.
PMID- 28498899
TI - MAGenTA: a Galaxy implemented tool for complete Tn-Seq analysis and data
visualization.
AB - Motivation: Transposon insertion sequencing (Tn-Seq) is a microbial systems-level
tool, that can determine on a genome-wide scale and in high-throughput, whether a
gene, or a specific genomic region, is important for fitness under a specific
experimental condition. Results: Here, we present MAGenTA, a suite of analysis
tools which accurately calculate the growth rate for each disrupted gene in the
genome to enable the discovery of: (i) new leads for gene function, (ii) non
coding RNAs; (iii) genes, pathways and ncRNAs that are involved in tolerating
drugs or induce disease; (iv) higher order genome organization; and (v) host
factors that affect bacterial host susceptibility. MAGenTA is a complete Tn-Seq
analysis pipeline making sensitive genome-wide fitness (i.e. growth rate)
analysis available for most transposons and Tn-Seq associated approaches (e.g.
TraDis, HiTS, IN-Seq) and includes fitness (growth rate) calculations, sliding
window analysis, bottleneck calculations and corrections, statistics to compare
experiments and strains and genome-wide fitness visualization. Availability and
implementation: MAGenTA is available at the Galaxy public ToolShed repository and
all source code can be found and are freely available at
https://vanopijnenlab.github.io/MAGenTA/ . Contact: vanopijn@bc.edu.
Supplementary information: Supplementary data are available at Bioinformatics
online.
PMID- 28498902
TI - Reply: Beneficial effect of interleukin-2-based immunomodulation in Alzheimer
like pathology.
PMID- 28498901
TI - ECCO-ESCP Consensus on Surgery for Crohn's Disease.
PMID- 28498903
TI - Efficacy and safety of inhaled anaesthetic for postoperative sedation during
mechanical ventilation in adult cardiac surgery patients: a systematic review and
meta-analysis.
AB - The aim was to evaluate the efficacy and safety of volatile anaesthetic for
postoperative sedation in adult cardiac surgery patients through a systematic
review and meta-analysis. We retrieved randomized controlled trials from MEDLINE,
EMBASE, CENTRAL, Web of Science, clinical trials registries, conference
proceedings, and reference lists of included articles. Independent reviewers
extracted data, including patient characteristics, type of intraoperative
anaesthesia, inhaled anaesthetic used, comparator sedation, and outcomes of
interest, using pre-piloted forms. We assessed risk of bias using the Cochrane
Tool and evaluated the strength of the evidence using the GRADE approach. Eight
studies enrolling 610 patients were included. Seven had a high and one a low risk
of bias. The times to extubation after intensive care unit (ICU) admission and
sedation discontinuation were, respectively, 76 [95% confidence interval (CI)
150 to - 2, I2=79%] and 74 min (95% CI - 126 to - 23, I2=96%) less in patients
who were sedated using volatile anaesthetic. There was no difference in ICU or
hospital length of stay. Patients who received volatile anaesthetic sedation had
troponin concentrations that were 0.71 ng ml-1 (95% CI 0.23-1.2) lower than
control patients. Reporting on other outcomes was varied and not suitable for
meta-analysis. Volatile anaesthetic sedation may be associated with a shorter
time to extubation after cardiac surgery but no change in ICU or hospital length
of stay. It is associated with a significantly lower postoperative troponin
concentration, but the impact of this on adverse cardiovascular outcomes is
uncertain. Blinded randomized trials using intention-to-treat analysis are
required. PROSPERO registry number: 2016:CRD42016033874. Available from
http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016033874.
PMID- 28498904
TI - The ACEF II Risk Score for cardiac surgery: updated but still parsimonious.
AB - Aims: The age, creatinine, and ejection fraction (ACEF) score was introduced in
2009 and is presently included in the guidelines for myocardial revascularization
of the European Society of Cardiology and Association for Cardio-Thoracic Surgery
as a risk stratification tool for surgical and percutaneous myocardial
revascularization. The present study introduces an updated version of the ACEF
(ACEF II) inclusive of emergency surgery and pre-operative anaemia. Methods and
results: The development series includes 7011 consecutive cardiac surgery
patients operated at a single institution. The validation series includes 1687
consecutive cardiac surgery patients operated in a different institution. The
five factors included in the ACEF II were assessed in a multivariable logistic
regression model testing their independent role as predictors of operative (in
hospital or 30 days after surgery) mortality. Based on the odds ratio of each
predictor, the ACEF II score is calculated as age(years)/ejection fraction (%).
Additional points are attributed to a serum creatinine level > 2 mg/dL (2
points), emergency surgery (3 points) and anaemia [haematocrit (HCT) < 36%, 0.2
points per each HCT point below 36%]. The final model was well calibrated.
Discrimination of the ACEF II (c-statistics 0.814) was significantly (P = 0.041)
better than the ACEF (c-statistics 0.773) and equal to the EuroSCORE II. In the
external validation, the ACEF II confirmed a better discrimination than the ACEF
and good calibration properties. Conclusion: The ACEF II allows the inclusion of
emergency patients and, through a re-modulation of the coefficients and the
inclusion of anaemia, appears more adequate to the present cardiac surgery
scenario.
PMID- 28498905
TI - Basiliximab for posterior reversible encephalopathy syndrome after lung
transplantation.
AB - Posterior reversible encephalopathy syndrome is a neurological complication
associated with calcineurin inhibitors. There is no consensus regarding the
continuation of calcineurin inhibitors in the event of posterior reversible
encephalopathy syndrome. We report 3 cases of posterior reversible encephalopathy
syndrome among 155 lung transplant recipients (1.9%). The calcineurin inhibitor
trough level exceeded the therapeutic range in only 1 case. Our findings
demonstrate that temporary cessation of calcineurin inhibitors and administration
of basiliximab may be effective strategies for managing posterior reversible
encephalopathy syndrome.
PMID- 28498906
TI - Heap: a highly sensitive and accurate SNP detection tool for low-coverage high
throughput sequencing data.
AB - Recent availability of large-scale genomic resources enables us to conduct so
called genome-wide association studies (GWAS) and genomic prediction (GP)
studies, particularly with next-generation sequencing (NGS) data. The
effectiveness of GWAS and GP depends on not only their mathematical models, but
the quality and quantity of variants employed in the analysis. In NGS single
nucleotide polymorphism (SNP) calling, conventional tools ideally require more
reads for higher SNP sensitivity and accuracy. In this study, we aimed to develop
a tool, Heap, that enables robustly sensitive and accurate calling of SNPs,
particularly with a low coverage NGS data, which must be aligned to the reference
genome sequences in advance. To reduce false positive SNPs, Heap determines
genotypes and calls SNPs at each site except for sites at the both ends of reads
or containing a minor allele supported by only one read. Performance comparison
with existing tools showed that Heap achieved the highest F-scores with low
coverage (7X) restriction-site associated DNA sequencing reads of sorghum and
rice individuals. This will facilitate cost-effective GWAS and GP studies in this
NGS era. Code and documentation of Heap are freely available from
https://github.com/meiji-bioinf/heap (29 March 2017, date last accessed) and our
web site (http://bioinf.mind.meiji.ac.jp/lab/en/tools.html (29 March 2017, date
last accessed)).
PMID- 28498907
TI - Complicated infective aortic endocarditis: comparison of different surgical
strategies.
AB - OBJECTIVES: The choice of substitute during aortic valve replacement for
infective endocarditis (IE) is still widely debated. We retrospectively reviewed
all patients operated for aortic IE and compared groups according to the
complexity of IE and substitutes implanted. METHODS: From 2000 to 2015, 187
patients were treated using stentless bioprostheses (SBP) as root replacement (n
= 30), mechanical prostheses (MP, n = 45) or stented bioprostheses (SP, n = 112)
(mean follow-up 4.6 years, survival data 100% complete). RESULTS: MP patients
were younger (42.5 +/- 10.7 vs 57.2 +/- 16.9 years [SBP], 59.1 +/- 14.1 years
[SP], P < 0.01), but rates of intravenous drug use and chronic dialysis were not
different. SBP patients more often had root involvement (83.3% vs 33.3% [MP],
25.9% [SP], P < 0.01) and prosthetic valve endocarditis (53.3% vs 6.7% [MP],
12.5% [SP], P < 0.01). In-hospital complications and length of stay were not
different. Thirty-day mortality was 13.3% [SBP], 6.7% [MP] and 12.5% [SP] (P =
0.53). Five-year survival tended to be superior in SBP (83.3% vs 77.6% [MP],
67.1% [SP], P = 0.09). In patients with complicated IE (root involvement or
prosthetic valve endocarditis, n = 77), SBP had superior long-term survival
(86.9% vs 81.3% [MP], 57.2% [SP], PSBP/MP = 0.07, PSBP/SP = 0.05). No early
reinfection (<90 days) occurred in SBP vs 4.4% [MP] and 7.1% [SP] (P = 0.29).
Reoperation for late reinfection occurred in 6.7% [SBP] vs 11.1% [MP] and 12.5%
[SP] (P = 0.65). Prosthesis failure occurred in 3.3% [SBP] and 1.8% [SP] (P =
0.52). CONCLUSIONS: Use of SBP provides favourable outcomes in patients with IE
with low rates of reinfection and valve deterioration. It seems to be an optimal
device in patients with complex IE.
PMID- 28498908
TI - Development, Validation and Application of a Stability Indicating HPLC Method to
Quantify Lidocaine from Polyethylene-co-Vinyl Acetate (EVA) Matrices and
Biological Fluids.
AB - An efficient and cost-effective quantification procedure for lidocaine by HPLC
has been developed to estimate lidocaine from an EVA matrix, plasma, peritoneal
fluid and intra-articular fluid (IAF). This method guarantees the resolution of
lidocaine from the degradation products obtained from alkaline and oxidative
stress. Chromatographic separation of lidocaine was achieved with a retention
time of 7 min using a C18 column with a mobile phase comprising acetonitrile and
potassium dihydrogen phosphate buffer (pH 5.5; 0.02 M) in the ratio of 26:74 at a
flow rate of 1 mL min-1 with detection at 230 nm. Instability of lidocaine was
observed to an oxidizing (0.02% H2O2) and alkaline environments (0.1 M NaOH). The
calibration curve was found to be linear within the concentration range of 0.40
50.0 MUg/mL. Intra-day and inter-day accuracy ranged between 95.9% and 99.1%,
with precision (% RSD) below 6.70%. The limit of quantification and limit of
detection were 0.40 MUg/mL and 0.025 MUg/mL, respectively. The simple extraction
method described enabled the quantification of lidocaine from an EVA matrix using
dichloromethane as a solvent. The assay and content uniformity of lidocaine
within an EVA matrix were 103 +/- 3.60% and 100 +/- 2.60%, respectively. The
ability of this method to quantify lidocaine release from EVA films was also
demonstrated. Extraction of lidocaine from plasma, peritoneal fluid and IAF
followed by HPLC analysis confirmed the utility of this method for ex vivo and in
vivo studies where the calibration plot was found to be linear from 1.60 to 50.0
MUg/mL.
PMID- 28498909
TI - Beneficial effect of interleukin-2-based immunomodulation in Alzheimer-like
pathology.
PMID- 28498910
TI - Extra-anatomical bypass in complex and recurrent aortic coarctation and
hypoplastic arch.
AB - OBJECTIVES: Our goal was to report the selection schemes, technical variations
and long-term outcome of extra-anatomical bypass to correct complex, recurrent
aortic coarctation and hypoplastic aortic arch. METHODS: Between 1989 and 2012,
53 patients (mean age 13.2 +/- 4.3, median 11.6, range 9-23 years) with complex
aortic coarctation (n = 33; long-segment hypoplastic aortic arch in 15),
recurrent coarctation (n = 20; anastomosic pseudoaneurysm in 10), underwent
correction using extra-anatomical bypass, either with (n = 18: femoral bypass =
13, left heart bypass = 5) or without (n = 35) extracorporeal circulation via a
left lateral thoracotomy (n= 48) and combined median sternotomy and median
laparotomy (n = 5). The decision to use extracorporeal circulation was based on
the anatomical location of the coarctation, the length of the hypoplasia and a
history of previous repair. Preoperatively, mean systolic blood pressure was 130
+/- 30 mmHg at rest and 180 +/- 40 mmHg during exercise, with a mean pressure
gradient of 80 +/- 11.6 (range 40-120) mmHg. RESULTS: Various extra-anatomical
bypass strategies included left subclavian artery to descending aorta (n = 38),
ascending aorta to left subclavian artery (n = 3), ascending aorta to descending
aorta (n = 4), aortic arch to descending aorta (n = 3) and ascending aorta to
abdominal aorta (n = 5). Graft size (median 18, range 10-26, mm) was chosen
according to the diameter of the vessel proximal and distal to the planned graft.
No operative deaths, paraplegia or abdominal malperfusion occurred. The mean
reduction in systolic blood pressure was 60 +/- 25 mmHg without pressure
gradients. During a mean follow-up of 18.3 +/- 3.7 years, there were no
reoperations, graft complications or pseudoaneurysm formation on anastomotic
sites. Seven (11.6%) patients are on antihypertensive medications. No patient
presented with claudication nor did anyone experience orthostatic problems from
the steal phenomenon. CONCLUSIONS: Extra-anatomical bypass is safe, an effective
technique, and achieves satisfactory long-term results.
PMID- 28498911
TI - Different Chromatographic Methods for Simultaneous Determination of Mefenamic
Acid and Two of Its Toxic Impurities.
AB - Two sensitive, accurate and precise chromatographic methods mentioned as TLC
densitometric method and RP-HPLC-DAD method, were developed and validated for the
simultaneous determination of mefenamic acid (MEF) and its two toxic impurities,
benzoic acid (BA) and 2,3-dimethylaniline (DMA). In the proposed TLC
densitometric method a developing system consisting of chloroform:acetone:acetic
acid:ammonia solution(70:30:2:2, v/v/v/v) was used, TLC aluminum plates 60 F254
was used as a stationary phase and the separated bands were UV-scanned at 225 nm.
While the proposed RP-HPLC-DAD method depended on chromatographic separation on
C18 column using 0.05 M KH2PO4 buffer: acetonitrile (40:60, v/v) as a mobile
phase at constant flow rate of 1 mL/min with UV detection at 225 nm. Linear
relationships were obtained in the ranges of 0.3-2, 0.3-2 and 0.3-1.8 MUg/band
(for TLC-densitometric method) and in the ranges of 7-50, 10-50 and 7-50 MUg/mL
(for HPLC-DAD method) for MEF, BA and DMA, respectively. Factors affecting the
developed methods have been studied and optimized. Moreover ,the proposed methods
were successfully applied for determination of the studied drug in its
pharmaceutical dosage form. The methods showed no significance difference when
compared with the reported method using F-test and Student's-t test. The low of
detection and quantization limits of the proposed methods get them suitable for
quality control and stability studies of MEF in pharmaceutical formulation. The
developed methods have advantages of being more selective and sensitive than the
published methods.
PMID- 28498912
TI - Data Resource Profile: Seeding Success: a cross-sectoral data resource for early
childhood health and development research in Australian Aboriginal and non
Aboriginal children.
PMID- 28498914
TI - Bibliometric analysis and curriculum mapping of travel medicine research.
AB - Evidence-based travel medicine requires that research priorities reflect the wide
knowledge base of this discipline. Bibliometric analysis of articles published in
Journal of Travel Medicine yielded the following results: epidemiology (6%, n =
105); immunology/vaccinology (8.5%, n = 148); pre-travel assessment/consultation
(30.5%, n = 533); diseases contracted during travel (48.3%, n = 843); other
clinical conditions associated with travel (6.8%, n = 119); post-travel
assessment (5.2%, n = 91) and administrative and general travel medicine issues
(6%, n = 105).
PMID- 28498915
TI - Adults of Lasioderma serricorne and Stegobium paniceum (Anobiidae: Coleoptera)
Are Attracted to Ultraviolet (UV) Over Blue Light LEDs.
AB - Two species, the cigarette beetle Lasioderma serricorne (F.) and the drugstore
beetle Stegobium paniceum (L.), are particularly important stored-product pests
because they damage dry food. A previous study showed that L. serricorne adults
are attracted more to ultraviolet (UV) and blue light wave ranges more than
others such as turquoise, green, yellow, red, and warm white. However, the
previous study did not equalize the amounts of light. The study also evaluated
the attractiveness by the numbers of L. serricorne individuals that were lured to
LED lights in a small box in the laboratory. In some storehouses, damage by S.
paniceum is more serious and establishment of an effective monitoring tool is
required. Therefore, in the present study, attractions of these beetles to UV and
blue light traps were compared to develop a tool to monitor the beetle pests.
First, adult L. serricorne and S. paniceum beetles were provided with UV- and
blue-LED panels whose light intensities were equalized in the laboratory, and the
walking and flying paths of each adult were recorded and measured. As a result,
adults were clearly attracted to the side of UV-LED panel by walking compared to
the blue one. Second, we compared the numbers of cigarette beetles collected by
sticky sheets that were set in the back of UV or blue-light LED traps in a real
storehouse. The results showed that these beetles were significantly more
attracted to UV than blue-light LED traps, indicating the UV-LED trap is a
powerful tool to monitor these two pest species.
PMID- 28498913
TI - The management of menopause in women with a history of endometriosis: a
systematic review.
AB - BACKGROUND: Endometriosis is typically regarded as a premenopausal disease,
resolving after natural or iatrogenic menopause due to declining oestrogen
levels. Nonetheless, case reports over the years have highlighted the incidence
of recurrent postmenopausal endometriosis. It is now clear that both recurrence
and malignant transformation of endometriotic foci can occur in the
postmenopausal period. Postmenopausal women are commonly treated with hormone
replacement therapy (HRT) to treat climacteric symptoms and prevent bone loss;
however, HRT may reactivate endometriosis and stimulate malignant transformation
in women with a history of endometriosis. Given the uncertain risks of initiating
HRT, it is difficult to determine the best menopausal management for this group
of women. OBJECTIVE AND RATIONAL: The aim of this study was to systematically
review the existing literature on management of menopausal symptoms in women with
a history of endometriosis. We also aimed to evaluate the published literature on
the risks associated with HRT in these women, and details regarding optimal
formulations and timing (i.e. initiation and duration) of HRT. SEARCH METHODS:
Four electronic databases (MEDLINE via OVID, Embase via OVID, PsycINFO via OVID
and CINAHL via EbscoHost) were searched from database inception until June 2016,
using a combination of relevant controlled vocabulary terms and free-text terms
related to 'menopause' and 'endometriosis'. Inclusion criteria were: menopausal
women with a history of endometriosis and menopausal treatment including HRT or
other preparations. Case reports/series, observational studies and clinical
trials were included. Narrative review articles, organizational guidelines and
conference abstracts were excluded, as were studies that did not report on any
form of menopausal management. Articles were assessed for risk of bias and
quality using GRADE criteria. OUTCOMES: We present a synthesis of the existing
case reports of endometriosis recurrence or malignant transformation in women
undergoing treatment for menopausal symptoms. We highlight common presenting
symptoms, potential risk factors and outcomes amongst the studies. Sparse high
quality evidence was identified, with few observational studies and only two
randomized controlled trials. Given this paucity of data, no definitive
conclusions can be drawn concerning risk. WIDER IMPLICATIONS: Due to the lack of
high-quality studies, it remains unclear how to advise women with a history of
endometriosis regarding the management of menopausal symptoms. The absolute risk
of disease recurrence and malignant transformation cannot be quantified, and the
impact of HRT use on these outcomes is not known. Multicentre randomized trials
or large observational studies are urgently needed to inform clinicians and
patients alike.
PMID- 28498916
TI - Effects of the Activation of Three Major Hepatic Akt Substrates on Glucose
Metabolism in Male Mice.
AB - Insulin suppresses glucose output from the liver via Akt activation; however,
which substrate of Akt plays the major role in transducing this effect is
unclear. We tested the postnatal expression of Akt-unresponsive, constitutively
active mutants of three major Akt substrates widely considered to regulate
glucose metabolism [i.e., FoxO1, PGC1alpha, and glycogen synthase kinase-3beta
(GSK3beta)] using adenoviral gene delivery to the mouse liver. We performed
physiological hyperinsulinemic-euglycemic clamp studies using these mice under
awake and nonrestrained conditions with blood sampling via an arterial catheter.
Hepatic expression of constitutively active FoxO1 induced significant hepatic and
systemic insulin resistance. However, neither the expression of constitutively
active PGC1alpha nor that of GSK3beta significantly changed insulin sensitivity.
Simultaneous expression of all three mutants together induced no further insulin
resistance compared with that of the FoxO1 mutant. The glycogen content in the
liver was significantly reduced by constitutively active GSK3beta expression. In
cultured hepatocytes, constitutively active PGC1alpha induced markedly stronger
transcriptional enhancement of gluconeogenic key enzymes than did constitutively
active FoxO1. From these results, we conclude that FoxO1 has the most prominent
role in transducing insulin's effect downstream from Akt to suppress hepatic
glucose output, involving mechanisms independent of the transcriptional
regulation of key gluconeogenic enzymes.
PMID- 28498917
TI - The New Genomics: What Molecular Databases Can Tell Us About Human Population
Variation and Endocrine Disease.
AB - Major recent advances in genetics and genomics present unique opportunities for
enhancing our understanding of human physiology and disease predisposition. Here
I demonstrate how analysis of genomic information can provide new insights into
endocrine systems, using the human growth hormone (GH) signaling pathway as an
illustrative example. GH is essential for normal postnatal growth in children,
and plays important roles in other biological processes throughout life. GH
actions are mediated by the GH receptor, primarily via the JAK2 protein tyrosine
kinase and the STAT5B transcription factor, and inactivating mutations in this
pathway all lead to impaired somatic growth. Variation in GH signaling genes has
been evaluated using DNA sequence data from the Exome Aggregation Consortium, a
compendium of information from >60,000 individuals. Results reveal many potential
missense and other alterations in the coding regions of GH1, GHR, JAK2, and
STAT5B, with most changes being uncommon. The total number of different alleles
per gene varied by ~threefold, from 101 for GH1 to 338 for JAK2. Several known
disease-linked mutations in GH1, GHR, and JAK2 were present but infrequent in the
population; however, three amino acid changes in GHR were sufficiently prevalent
(~4% to 44% of chromosomes) to suggest that they are not disease causing.
Collectively, these data provide new opportunities to understand how genetically
driven variability in GH signaling and action may modify human physiology and
disease.
PMID- 28498918
TI - Expression and Activity of the Small RhoGTPase Cdc42 in Blood Cells of Older
Adults Are Associated With Age and Cardiovascular Disease.
AB - The small RhoGTPase Cdc42 is mechanistically linked to aging of multiple tissues
and to rejuvenation of hematopoietic stem cells in mice. However, data validating
Cdc42 activity and expression as biomarker for aging in humans are still missing.
Here, we hypothesized that Cdc42 might serve as a novel biomarker of aging in
older adults and therefore we determined Cdc42 activity and expression levels in
peripheral blood cells from a cohort of 196 donors. We investigated the
association of these parameters with both chronological and biological aging. We
also tested in this cohort of older adults a recently published algorithm
determining chronological age based on DNA methylation profiles. A positive
correlation with chronological age was found for both the level of Cdc42 mRNA and
the level of active Cdc42 protein (the GTP bound form). Notably, the level of
Cdc42 mRNA as well as total protein showed a specific strong association to
cardiovascular disease and Cdc42 mRNA levels also to a history of myocardial
infarction. In summary, these data validate Cdc42 as a blood biomarker of both
chronological aging as well as aging-associated diseases like cardiovascular
disease and myocardial infarction.
PMID- 28498919
TI - Chemicogenetic Restoration of the Prefrontal Cortex to Amygdala Pathway
Ameliorates Stress-Induced Deficits.
AB - Corticosteroid stress hormones exert a profound impact on cognitive and emotional
processes. Understanding the neuronal circuits that are altered by chronic stress
is important for counteracting the detrimental effects of stress in a brain
region- and cell type-specific manner. Using the chemogenetic tool, Designer
Receptors Exclusively Activated by Designer Drugs (DREADDs), which enables the
remote, noninvasive and long-lasting modulation of cellular activity and signal
transduction in discrete neuronal populations in vivo, we sought to identify the
specific pathways that play an essential role in stress responses. We found that
prolonged severe stress induced the diminished glutamatergic projection from
pyramidal neurons in prefrontal cortex (PFC) to GABAergic interneurons in
basolateral amygdala (BLA), leading to the loss of feedforward inhibition and
ensuing hyperexcitability of BLA principal neurons, which caused a variety of
behavioral abnormalities. Activating PFC pyramidal neurons with hM3D(Gq) DREADD
restored the functional connection between PFC and BLA in stressed animals,
resulting in the rescue of recognition memory, normalization of locomotor
activity and reduction of aggressive behaviors. Inhibiting BLA principal neurons
directly with hM4D(Gi) DREADD also blocked BLA hyperactivity and aggressive
behaviors in stressed animals. These results have offered an effective avenue to
counteract the stress-induced disruption of circuitry homeostasis.
PMID- 28498920
TI - Copy number variation of functional RBMY1 is associated with sperm motility: an
azoospermia factor-linked candidate for asthenozoospermia.
AB - STUDY QUESTION: What is the influence of copy number variation (CNV) in
functional RNA binding motif protein Y-linked family 1 (RBMY1) on spermatogenic
phenotypes? SUMMARY ANSWER: The RBMY1 functional copy dosage is positively
correlated with sperm motility, and dosage insufficiency is an independent risk
factor for asthenozoospermia. WHAT IS KNOWN ALREADY: RBMY1, a multi-copy gene
expressed exclusively in the adult testis, is one of the most important
candidates for male infertility in the azoospermia factor (AZF) region of the Y
chromosome. RBMY1 encodes an RNA-binding protein that serves as a pre-mRNA
splicing regulator during spermatogenesis, and male mice deficient in Rbmy are
sterile. STUDY DESIGN, SIZE, DURATION: A total of 3127 adult males were recruited
from 2009 to 2016; of this group, the dosage of RBMY1 functional copy were
investigated in 486 fertile males. In the remaining 2641 males with known
spermatogenesis status, 1070 Y-chromosome haplogroup (Y-hg) O3* or O3e carriers
without chromosomal aberration or known AZF structure mutations responsible for
spermatogenic impairment, including 506 men with normozoospermia and 564 men with
oligozoospermia or/and asthenozoospermia, were screened, and the RBMY1 functional
copy dosage and copy conversion were determined to explore their associations
with sperm phenotypes. The correlation between RBMY1 dosage and its mRNA level or
RBMY1 protein level and the correlation between sperm RBMY1 level and motility
were analysed in 15 testis tissue samples and eight semen samples. Ten additional
semen samples were used to confirm the subcellular localization of RBMY1 in
individual sperm. PARTICIPANTS/MATERIALS, SETTING, METHODS: All the Han
volunteers donating whole blood, semen and testis tissue were from southwest
China. RBMY1 copy number, copy conversion, mRNA/protein amount and protein
location in sperm were detected using the AccuCopy(r) assay method, paralog ratio
test, quantitative PCR, western blotting and immunofluorescence staining methods,
respectively. MAIN RESULTS AND THE ROLE OF CHANCE: This study identified Y-hg
independent CNV of functional RBMY1 in the enrolled population. A difference in
the distribution of RBMY1 copy number was observed between the group with normal
sperm motility and the group with asthenozoospermia. A positive correlation
between the RBMY1 copy dosage and sperm motility was identified, and the males
with fewer than six copies of RBMY1 showed an elevated risk for asthenozoospermia
relative to those with six RBMY1 copies, the most common dosage in the
population. The RBMY1 copy dosage was positively correlated with its mRNA and
protein level in the testis. Sperm with high motility were found to carry more
RBMY1 protein than those with relatively low motility. The RBMY1 protein was
confirmed to predominantly localize in the neck and mid-piece region of sperm as
well as the principal piece of the sperm tail. Our population study completes a
chain of evidence suggesting that RBMY1 influences the susceptibility of males to
asthenozoospermia by modulating sperm motility. LIMITATIONS REASONS FOR CAUTION:
High sequence similarity between the RBMY1 functional copies and a large number
of pseudogenes potentially reduces the accuracy of the copy number detection. The
mechanism underlying the CNV in RBMY1 is still unclear, and the effect of the
structural variations in the RBMY1 copy cluster on the copy dosage of other
protein-coding genes located in the region cannot be excluded, which may
potentially bias our observations. WIDER IMPLICATIONS OF THE FINDINGS:
Asthenozoospermia is a multi-factor complex disease with a limited number of
proven susceptibility genes. This study identified a novel genomic candidate
independently contributing to the condition, enriching our understanding of the
role of AZF-linked genes in male reproduction. Our finding provides insight into
the physiological and pathological characteristics of RBMY1 in terms of sperm
motility, supplies persuasive evidence of the significance of RBMY1 copy number
analysis in the clinical counselling of male infertility resulting from
asthenozoospermia. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by
the National Natural Science Foundation of China (Nos. 81370748 and 30971598).
The authors have no conflicts of interest.
PMID- 28498921
TI - A meta-analysis of the use of rifaximin to prevent travellers' diarrhoea.
AB - Background: Travellers' diarrhoea affects tens of millions of people travelling
to less developed countries or regions annually. There are positive reports of
the use of rifaximin, a non-absorbed, gut-selective antibiotic to prevent
travellers' diarrhoea. This study will critically review and analyse clinical
trials on the subject. Methods: Using the keywords [diarrhoea OR diarrhoea OR
travel*] AND [rifaximin OR xifaxan OR xifaxanta OR normix OR rifagut], a
preliminary search on the PubMed and Ovid databases yielded 411 papers published
in English between 1 January 1988 and 1 July 2016. Of these, there were only five
relevant clinical trials. Results: The clinical trials were double-blind, placebo
controlled, randomized trials with a total of 879 subjects. The meta-analysis
found significant reduction in risk of travellers' diarrhoea with rifaximin use
compared to placebo (pooled RR 0.478, 95% CI: 0.375-0.610, and P < 0.001). For
the entire travel and follow-up period, the risk of developing travellers'
diarrhoea was significantly greater in individuals receiving the placebo than
those receiving rifaximin (daily doses of 400-600 mg). Overall, rifaximin offered
significant protection rates of 48-72%, with lower protection rates for Asian
than Latin American countries. In terms of tolerability, similar rates of adverse
events were reported for the rifaximin and placebo group ( P > 0.05), with no
clinically significant or serious adverse events related to rifaximin use.
Conclusions: There is good evidence supporting the use of rifaximin as a
chemoprophylactic agent against travellers' diarrhoea, especially in individuals
who are at high risk of severe complications from acute infectious diarrhoea.
Rifaximin has an excellent tolerability/safety profile and demonstrated efficacy
against diarrhoeagenic Escherichia coli and even enteroinvasive bacteria such
Campylobacter species. Future studies should study the most effective dosing
regimen for rifaximin chemoprophylaxis, as well as profile local antimicrobial
resistance/susceptibility data in less developed regions to further guide
rifaximin use.
PMID- 28498922
TI - Outpatient vs Inpatient Anterior Cervical Discectomy and Fusion: A Population
Level Analysis of Outcomes and Cost.
AB - BACKGROUND: Outpatient anterior cervical discectomy and fusion (ACDF) is a
promising candidate for US healthcare cost reduction as several studies have
demonstrated that overall complications are relatively low and early discharge
can preserve high patient satisfaction, low morbidity, and minimal readmission.
OBJECTIVE: To compare clinical outcomes and associated costs between inpatient
and ambulatory setting ACDF. METHODS: Demographics, comorbidities, emergency
department (ED) visits, readmissions, reoperation rates, and 90-d charges were
retrospectively analyzed for patients undergoing elective ACDF in California,
Florida, and New York from 2009 to 2011 in State Inpatient and Ambulatory
Databases. RESULTS: A total of 3135 ambulatory and 46 996 inpatient ACDFs were
performed. Mean Charlson comorbidity index, length of stay, and mortality were
0.2, 0.4 d, and 0% in the ambulatory cohort and 0.4, 1.8 d, and 0.04% for
inpatients (P < .0001). Ambulatory patients were younger (48.0 vs 53.1) and more
likely to be Caucasian. One hundred sixty-eight ambulatory patients (5.4%)
presented to the ED within 30 d (mean 11.3 d), 51 (1.6%) were readmitted, and 5
(0.2%) underwent reoperation. Among inpatient surgeries, 2607 patients (5.5%)
presented to the ED within 30 d (mean 9.7 d), 1778 (3.8%) were readmitted (mean
6.3 d), and 200 (0.4%) underwent reoperation. Higher Charlson comorbidity index
increased rate of ED visits (ambulatory operating room [OR] 1.285, P < .05;
inpatient OR 1.289, P < .0001) and readmission (ambulatory OR 1.746, P < .0001;
inpatient OR 1.685, P < .0001). Overall charges were significantly lower for
ambulatory ACDFs ($33 362.51 vs $74 667.04; P < .0001). CONCLUSION: ACDF can be
performed in an ambulatory setting with comparable morbidity and readmission
rates, and lower costs, to those performed in an inpatient setting.
PMID- 28498923
TI - Preventive measures for "Pet Friendly" lodging facilities: association of
Leishmaniasis expansion route in Sao Paulo and preventive measures for regional
animals displacement.
PMID- 28498924
TI - Major role of pKpQIL-like plasmids in the early dissemination of KPC-type
carbapenemases in the UK.
AB - Objectives: Klebsiella pneumoniae carbapenemase (KPC)-producing
Enterobacteriaceae were first seen in the UK in 2003 and have been increasingly
reported since 2010, largely owing to an ongoing outbreak in North-West England.
We examined the role of clonal spread and plasmid transmission in their
emergence. Methods: Isolates comprised KPC-positive K. pneumoniae ( n = 33),
Escherichia coli ( n = 7) and Enterobacter spp. ( n = 4) referred to the
national reference laboratory between 2008 and 2010 from 17 UK centres, including
three in North-West England. Isolates were typed by MLST. Plasmids were
transferred by electroporation and characterized by PCR or sequencing. PCR
screening assays were developed to distinguish plasmid pKpQIL variants. Results:
The K. pneumoniae isolates included 10 STs, of which three belonged to clonal
group (CG) 258. CG258 ( n = 19) isolates were detected in 13 centres but
accounted for only 7/19 (36.8%) of those from North-West England. Most KPC
producers (37/44, 84.1%), including 16/19 CG258 K. pneumoniae , carried bla KPC
on IncFII K2 plasmids. Sequencing of a subset of these plasmids ( n = 11)
revealed similarities with published pKpQIL. One variant, pKpQIL-UK [identified
in K. pneumoniae CG258 ( n = 5) and ST468 ( n = 1) isolates from distinct
centres] had only a few nucleotide changes from classical pKpQIL, whereas pKpQIL
D1 ( n = 1) and pKpQIL-D2 ( n = 4), from isolates of various species in the
North-West, harboured large variations, reflecting replacement of the
partitioning and replication functions and potentially thereby facilitating
spread. PCR revealed that 36/37 (97.3%) IncFII K2 -type plasmids in KPC-positive
isolates had pKpQIL markers. Conclusions: pKpQIL-like plasmids played a major
role in the early dissemination of KPC enzymes in the UK.
PMID- 28498925
TI - A case report of anaphylaxis to Typhoid Vaccine Live Oral Ty21a (Vivotif).
AB - Typhoid Vaccine Live Oral Ty21a (Vivotif) is typically well tolerated, and
adverse events are infrequent and mild. To the best of the authors' knowledge,
only one prior anaphylactic reaction has previously been reported. We present a
case of anaphylaxis related to Vivotif, in which a 66-year-old male with no
medical comorbidities developed anaphylaxis following the third of a four-dose
course (in the absence of concomitant vaccination administration), which
consisted of tongue swelling, difficulty breathing, abdominal discomfort and
rash. He was managed with epinephrine, corticosteroids and antihistamines.
PMID- 28498926
TI - Categorizing body mass index biases assessment of the association with post
coronary artery bypass graft mortality.
AB - OBJECTIVES: The high prevalence of obesity makes accurately estimating the impact
of anthropometric measures on cardiac surgery outcomes critical. The Society of
Thoracic Surgeons coronary artery bypass graft (CABG) surgery risk model includes
body surface area (as a continuous variable, using spline functions), but most
studies apply various categorizations of body mass index (BMI)-contributing to
the contradictory published findings. We assessed the association between BMI
(modelled as a continuous variable without assumptions of linearity) and CABG
operative mortality and examined the impact of applying previous studies' BMI
modelling strategies. METHODS: We identified 25 studies investigating the BMI
operative mortality association: 22 categorized BMI, 2 as a linear continuous
variable,1 used spline functions. Our cohort of 12 715 consecutive patients
underwent isolated CABG at 32 cardiac surgery programmes in North Texas from 1
January 2008-31 December 2012. BMI was modelled using restricted cubic spline
functions in a propensity-adjusted model (controlling for Society of Thoracic
Surgeons risk factors) estimating operative mortality. The analysis was repeated
using each categorization identified and modelling BMI as a linear continuous
variable. RESULTS: BMI (modelled with a restricted cubic spline) was
significantly associated with operative mortality (P < 0.0001). Risk was lowest
for BMI near 30 kg/m2 and highest below 20 kg/m2 and above 40 kg/m2. No
categorization, nor the linear continuous model, fully captured this association.
CONCLUSIONS: BMI is strongly associated with CABG operative mortality.
Categorizing BMI (or assuming a linear relationship) heavily biases estimates of
its association with post-CABG mortality. In general, smoothing techniques should
be used for all continuous risk factors to avoid bias.
PMID- 28498927
TI - Efficacy and safety of carbetocin given as an intravenous bolus compared with
short infusion for Caesarean section - double-blind, double-dummy, randomized
controlled non-inferiority trial.
AB - Background: Carbetocin is a synthetic oxytocin-analogue, which should be
administered as bolus according to manufacturer's recommendations. A higher speed
of oxytocin administration leads to increased cardiovascular side-effects. It is
unclear whether carbetocin administration as short infusion has the same efficacy
on uterine tone compared with bolus administration and whether haemodynamic
parameters differ. Methods: In this randomized, double-blind, non-inferiority
trial, women undergoing planned or unplanned Caesarean section (CS) under
regional anaesthesia received a bolus and a short infusion, only one of which
contained carbetocin 100 mcg (double dummy). Obstetricians quantified uterine
tone two, three, five and 10 min after cord-clamping by manual palpation using a
linear analogue scale from 0 to 100. We evaluated whether the lower limit of the
95% CI of the difference in maximum uterine tone within the first five min after
cord-clamping did not include the pre-specified non-inferiority limit of -10.
Results: Between December 2014 and November 2015, 69 patients were randomized to
receive carbetocin as bolus and 71 to receive it as short infusion. Maximal
uterine tone was 89 in the bolus and 88 in the short infusion group (mean
difference -1.3, 95% CI -5.7 to 3.1). Bp, calculated blood loss, use of
additional uterotonics, and side-effects were comparable. Conclusions:
Administration of carbetocin as short infusion does not compromise uterine tone
and has similar cardiovascular side-effects as a slow i.v. bolus. In accordance
with current recommendations for oxytocin, carbetocin can safely be administered
as short -infusion during planned or unplanned CS. Clinical trial registration:
ClinicalTrials.gov NCT02221531 and www.kofam.ch SNCTP000001197.
PMID- 28498928
TI - E2FM: an encrypted and compressed full-text index for collections of genomic
sequences.
AB - Motivation: Next Generation Sequencing (NGS) platforms and, more generally, high
throughput technologies are giving rise to an exponential growth in the size of
nucleotide sequence databases. Moreover, many emerging applications of nucleotide
datasets-as those related to personalized medicine-require the compliance with
regulations about the storage and processing of sensitive data. Results: We have
designed and carefully engineered E 2 FM -index, a new full-text index in minute
space which was optimized for compressing and encrypting nucleotide sequence
collections in FASTA format and for performing fast pattern-search queries. E 2
FM -index allows to build self-indexes which occupy till to 1/20 of the storage
required by the input FASTA file, thus permitting to save about 95% of storage
when indexing collections of highly similar sequences; moreover, it can exactly
search the built indexes for patterns in times ranging from few milliseconds to a
few hundreds milliseconds, depending on pattern length. Availability and
implementation: Source code is available at https://github.com/montecuollo/E2FM .
Contact: ferdinando.montecuollo@unicampania.it. Supplementary information:
Supplementary data are available at Bioinformatics online.
PMID- 28498929
TI - Multi-stakeholder perspectives in defining health-services quality in cataract
care.
AB - Objective: To develop a method to define a multi-stakeholder perspective on
health-service quality that enables the expression of differences in
systematically identified stakeholders' perspectives, and to pilot the approach
for cataract care. Design: Mixed-method study between 2014 and 2015. Setting:
Cataract care in the Netherlands. Participants: Stakeholder representatives.
Intervention(s): We first identified and classified stakeholders using
stakeholder theory. Participants established a multi-stakeholder perspective on
quality of cataract care using concept mapping, this yielded a cluster map based
on multivariate statistical analyses. Consensus-based quality dimensions were
subsequently defined in a plenary stakeholder session. Main outcome measure(s):
Stakeholders and multi-stakeholder perspective on health-service quality.
Results: Our analysis identified seven definitive stakeholders, as follows: the
Dutch Ophthalmology Society, ophthalmologists, general practitioners,
optometrists, health insurers, hospitals and private clinics. Patients, as
dependent stakeholders, were considered to lack power by other stakeholders;
hence, they were not classified as definitive stakeholders. Overall, 18
stakeholders representing ophthalmologists, general practitioners, optometrists,
health insurers, hospitals, private clinics, patients, patient federations and
the Dutch Healthcare Institute sorted 125 systematically collected indicators
into the seven following clusters: patient centeredness and accessibility,
interpersonal conduct and expectations, experienced outcome, clinical outcome,
process and structure, medical technical acting and safety. Importance scores
from stakeholders directly involved in the cataract service delivery process
correlated strongly, as did scores from stakeholders not directly involved in
this process. Conclusions: Using a case study on cataract care, the proposed
methods enable different views among stakeholders concerning quality dimensions
to be systematically revealed, and the stakeholders jointly agreed on these
dimensions. The methods helped to unify different quality definitions and
facilitated operationalisation of quality measurement in a way that was accepted
by relevant stakeholders.
PMID- 28498930
TI - Risk Factors for Intracranial Aneurysm Rupture: A Systematic Review.
AB - BACKGROUND: Intracranial aneurysm rupture prediction is poor, with only a few
risk factors for rupture identified and used in clinical practice. OBJECTIVE: To
provide an overview of all the risk factors (including genetic, molecular,
morphological, and hemodynamic factors) that have potential for use in clinical
practice. METHODS: We systematically searched PubMed and EMBASE and focused on
factors that can be easily assessed in clinical practice, might be used for
rupture prediction in clinical practice, and/or are potential targets for further
research. Studies were categorized according to methodological quality, and a
meta-analysis was performed, if possible. RESULTS: We included 102 studies
describing 144 risk factors that fulfilled predefined criteria. There was strong
evidence for the morphological factors irregular shape (studied in 4 prospective
cohort studies of high-quality, pooled odds ratio [OR] of 4.8 [95% confidence
interval 2.7-8.7]), aspect ratio (pooled OR 10.2 [4.3-24.6]), size ratio,
bottleneck factor, and height-to-width ratio to increase rupture risk. Moderate
level of evidence was found for presence of contact with the perianeurysmal
environment (pooled OR 3.5 [1.4-8.4]), unbalanced nature of this contact (pooled
OR 17.8 [8.3-38.5]), volume-to-ostium ratio, and direction of the aneurysm dome
(pooled OR 1.5 [1.2-1.9]). CONCLUSION: Irregular aneurysm shape was identified as
a risk factor with potential for use in clinical practice. The risk factors
aspect ratio, size ratio, bottleneck factor, height-to-width ratio, contact with
the perianeurysmal environment, volume-to-ostium ratio, and dome-direction should
first be confirmed in multivariate analysis and incorporated in prediction
models.
PMID- 28498932
TI - From CNTNAP2 to Early Expressive Language in Infancy: The Mediation Role of Rapid
Auditory Processing.
AB - Although it is clear that early language acquisition can be a target of CNTNAP2,
the pathway between gene and language is still largely unknown. This research
focused on the mediation role of rapid auditory processing (RAP). We tested RAP
at 6 months of age by the use of event-related potentials, as a mediator between
common variants of the CNTNAP2 gene (rs7794745 and rs2710102) and 20-month-old
language outcome in a prospective longitudinal study of 96 Italian infants. The
mediation model examines the hypothesis that language outcome is explained by a
sequence of effects involving RAP and CNTNAP2. The ability to discriminate
spectrotemporally complex auditory frequency changes at 6 months of age mediates
the contribution of rs2710102 to expressive vocabulary at 20 months. The indirect
effect revealed that rs2710102 C/C was associated with lower P3 amplitude in the
right hemisphere, which, in turn, predicted poorer expressive vocabulary at 20
months of age. These findings add to a growing body of literature implicating RAP
as a viable marker in genetic studies of language development. The results
demonstrate a potential developmental cascade of effects, whereby CNTNAP2 drives
RAP functioning that, in turn, contributes to early expressive outcome.
PMID- 28498931
TI - Protective effects of hot spring water drinking and radon inhalation on ethanol
induced gastric mucosal injury in mice.
AB - Radon therapy using radon (222Rn) gas is classified into two types of treatment:
inhalation of radon gas and drinking water containing radon. Although short- or
long-term intake of spa water is effective in increasing gastric mucosal blood
flow, and spa water therapy is useful for treating chronic gastritis and gastric
ulcer, the underlying mechanisms for and precise effects of radon protection
against mucosal injury are unclear. In the present study, we examined the
protective effects of hot spring water drinking and radon inhalation on ethanol
induced gastric mucosal injury in mice. Mice inhaled radon at a concentration of
2000 Bq/m3 for 24 h or were provided with hot spring water for 2 weeks. The
activity density of 222Rn ranged from 663 Bq/l (start point of supplying) to 100
Bq/l (end point of supplying). Mice were then orally administered ethanol at
three concentrations. The ulcer index (UI), an indicator of mucosal injury,
increased in response to the administration of ethanol; however, treatment with
either radon inhalation or hot spring water inhibited the elevation in the UI due
to ethanol. Although no significant differences in antioxidative enzymes were
observed between the radon-treated groups and the non-treated control groups,
lipid peroxide levels were significantly lower in the stomachs of mice pre
treated with radon or hot spring water. These results suggest that hot spring
water drinking and radon inhalation inhibit ethanol-induced gastric mucosal
injury.
PMID- 28498933
TI - Preliminary evaluation of discomfort glare from organic light-emitting diode and
edge-lit light-emitting diode lighting panels.
AB - The organic light-emitting diode (OLED) is an area light source, and its primary
competing technology is the edge-lit light-emitting diode (LED) panel. Both
technologies are similar in shape and appearance, but there is little
understanding of how people perceive discomfort glare (DG) from area sources. The
objective of this study was to evaluate the DG of these two technologies under
similar operating conditions. Additionally, two existing DG models were compared
to evaluate the correlation between predicted values and observed values. In an
earlier study, we found no statistically significant difference in human response
in terms of DG between OLED and edge-lit LED panels when the two sources produced
the same luminous stimulus. The range of testing stimulus was expanded to test
different panel luminances at three background illuminations. The results showed
no difference in perceived glare between the panels, and, as the background
illumination increased, the perceived glare decreased. In other words, both
appeared equally glary beyond a certain luminance and background illumination. We
then compared two existing glare models with the observed values and found that
one model showed a good estimation of how humans perceive DG. That model was
further modified to increase its power.
PMID- 28498935
TI - The association of changes in DNA methylation with temperature-dependent sex
determination in cucumber.
AB - Cucumber (Cucumis sativus L.) is characterized by its diverse and flexible sexual
types. Here, we evaluated the effect of low temperature (LT) exposure on cucumber
femaleness under short-day conditions. Shoot apices were subjected to whole
genome bisulfate sequencing (WGBS), mRNA-seq, and sRNA-seq. The results showed
that temperature had a substantial and global impact on transposable element (TE)
related small RNA-directed DNA methylation (RdDM) mechanisms, resulting in large
amounts of CHH-type cytosine demethylation. In the cucumber genome, TEs are
common in regions near genes that are also subject to DNA demethylation. TE-gene
interactions showed very strong reactions to LT treatment, as nearly 80% of the
differentially methylated regions (DMRs) were distributed in genic regions.
Demethylation near genes led to the co-ordinated expression of genes and TEs.
More importantly, genome-wide de novo methylation changes also resulted in small
amounts of CG- and CHG-type DMRs. Methylation changes in CG-DMRs located <600 bp
from the transcription start and end sites (TSSs/TESs) negatively correlated with
transcription changes in differentially expressed genes (DEGs), probably
indicating epiregulation. Ethylene is called the 'sex hormone' of cucumbers. We
observed the up-regulation of ethylene biosynthesis-related CsACO3 and the down
regulation of an Arabidopsis RAP2.4-like ethylene-responsive (AP2/ERF)
transcription factor, demonstrating the inferred epiregulation. Our study
characterized the response of the apex methylome to LT and predicted the possible
epiregulation of temperature-dependent sex determination (TSD) in cucumber.
PMID- 28498934
TI - Leveraging Genomic Data in Smoking Cessation Trials in the Era of Precision
Medicine: Why and How.
AB - Implications: This article outlines a framework for the consistent integration of
biological data/samples into smoking cessation pharmacotherapy trials, aligned
with the objectives of the recently unveiled Precision Medicine Initiative. Our
goal is to encourage and provide support for treatment researchers to consider
biosample collection and genotyping their existing samples as well as integrating
genetic analyses into their study design in order to realize precision medicine
in treatment of nicotine dependence.
PMID- 28498936
TI - A Phase 1 Dose-Escalation Study of Oral 5-Aminolevulinic Acid in Adult Patients
Undergoing Resection of a Newly Diagnosed or Recurrent High-Grade Glioma.
AB - BACKGROUND: The utility of oral 5-aminolevulinic acid (5-ALA)/protoporphyrin
fluorescence for the resection of high-grade gliomas is well documented. This
drug has received regulatory approval in Europe but awaits approval in the United
States. OBJECTIVE: To identify the appropriate dose and toxicity or harms of 5
ALA used for enhanced intraoperative visualization of malignant brain tumors,
reported from a single medical center in the United States. METHODS: Prior to
craniotomy for resection of a presumed high-grade glioma, individuals were given
oral 5-ALA as part of a rapid dose-escalation scheme. At least 3 patients were
selected for each dose level from 10 to 50 mg/kg in 10 mg/kg increments. Adverse
events, intensity of tumor fluorescence, and results of biopsies in areas of
tumor and the tumor bed under white light and deep blue light were recorded.
RESULTS: A total of 19 patients were studied in this phase 1 study. Serious
adverse events were unrelated to the ingestion of 5-ALA. At the highest dose
level studied (50 mg/kg), 2 out of 6 patients were observed to have transient
dermatologic redness and peeling. These were grade 1 adverse events, which were
not serious enough to be dose limiting. Patients at higher dose levels (>40
mg/kg) were more likely to have strong tumor fluorescence. There were no
instances of false positive fluorescence. CONCLUSION: The use of 5-ALA for brain
tumor fluorescence is safe and effective to a dose of 50 mg/kg. Dose-limiting
toxicity was not reached in this study.
PMID- 28498937
TI - The Prevalence of Anosmia and Associated Factors Among U.S. Black and White Older
Adults.
AB - Background: Olfactory impairment is common among older adults; however, data are
largely limited to whites. Methods: We conducted pooled analyses of two community
based studies: the Atherosclerosis Risk in Communities study (ARIC, 1,398 blacks
and 4,665 whites), and the Health, Aging, and Body Composition study (Health ABC,
958 blacks and 1,536 whites) to determine the prevalence of anosmia and
associated factors for black and white older adults in the United States.
Results: The overall prevalence of anosmia was 22.3% among blacks and 10.4% among
whites. Blacks had a markedly higher odds of anosmia compared to whites in age
and sex adjusted analyses (odds ratio [OR] 2.96, 95% confidence interval [CI] =
2.59-3.38). In both blacks and whites, higher anosmia prevalence was associated
with older age and male sex. The highest prevalence was found in black men 85
years or older (58.3%), and the lowest in white women aged 65-69 years (2.4%).
Higher education level, lower cognitive score, ApoE epsilon4, daytime sleepiness,
poorer general health status, lower body mass index, and Parkinson disease were
associated with higher prevalence of anosmia in one or both races. However, the
racial difference in anosmia remained statistically significant after adjusting
for these factors (fully adjusted OR = 1.76, 95%CI: 1.50-2.07). Results were
comparable between the two cohorts. Discussion: Anosmia is common in older
adults, particularly among blacks. Further studies are needed to identify risk
factors for anosmia and to investigate racial disparities in this sensory
deficit.
PMID- 28498938
TI - Healthcare Resource Utilization and Patient-Reported Outcomes Following Elective
Surgery for Intradural Extramedullary Spinal Tumors.
AB - BACKGROUND: Healthcare resource utilization and patient-reported outcomes (PROs)
for intradural extramedullary (IDEM) spine tumors are not well reported.
OBJECTIVE: To analyze the PROs, costs, and resource utilization 1 year following
surgical resection of IDEM tumors. METHODS: Patients undergoing elective spine
surgery for IDEM tumors and enrolled in a single-center, prospective,
longitudinal registry were analyzed. Baseline and postoperative 1-year PROs were
recorded. One-year spine-related direct and indirect healthcare resource
utilization was assessed. One-year resource use was multiplied by unit costs
based on Medicare national payment amounts (direct cost). Patient and caregiver
workday losses were multiplied by the self-reported gross-of-tax wage rate
(indirect cost). RESULTS: A total of 38 IDEM tumor patients were included in this
analysis. There was significant improvement in quality of life (EuroQol-5D),
disability (Oswestry and Neck Disability Indices), pain (Numeric rating scale
pain scores for back/neck pain and leg/arm pain), and general physical and mental
health (Short-form-12 health survey, physical and mental component scores) in
both groups 1 year after surgery (P < .0001). Eighty-seven percent (n = 33) of
patients were satisfied with surgery. The 1-year postdischarge resource
utilization including healthcare visits, medication, and diagnostic cost was
$4111 +/- $3596. The mean total direct cost was $23 717 +/- $7412 and indirect
cost was $5544 +/- $4336, resulting in total 1-year cost $29 177 +/- $9314.
CONCLUSION: Surgical resection of the IDEM provides improvement in patient
reported quality of life, disability, pain, general health, and satisfaction at 1
year following surgery. Furthermore, we report the granular costs of surgical
resection and healthcare resource utilization in this population.
PMID- 28498939
TI - Carbon utilization profiles of river bacterial strains facing sole carbon sources
suggest metabolic interactions.
AB - Microbial communities play a key role in water self-purification. They are
primary drivers of biogenic element cycles and ecosystem processes. However,
these communities remain largely uncharacterized. In order to understand the
diversity-heterotrophic activity relationship facing sole carbon sources, we
assembled a synthetic community composed of 20 'typical' freshwater bacterial
species mainly isolated from the Zenne River (Belgium). The carbon source
utilization profiles of each individual strain and of the mixed community were
measured in Biolog Phenotype MicroArrays PM1 and PM2A microplates that allowed
testing 190 different carbon sources. Our results strongly suggest interactions
occurring between our planktonic strains as our synthetic community showed
metabolic properties that were not displayed by its single components. Finally,
the catabolic performances of the synthetic community and a natural community
from the same sampling site were compared. The synthetic community behaved like
the natural one and was therefore representative of the latter in regard to
carbon source consumption.
PMID- 28498941
TI - Erratum.
PMID- 28498940
TI - Contribution of aerobic anoxygenic phototrophic bacteria to total organic carbon
pool in aquatic system of subtropical karst catchments, Southwest China: evidence
from hydrochemical and microbiological study.
AB - Aerobic anoxygenic phototrophic bacteria may play a particular role in carbon
cycling of aquatic systems. However, little is known about the interaction
between aerobic anoxygenic phototrophic bacteria and hydrochemistry in
groundwater-surface water exchange systems of subtropical karst catchments. We
carried out a detailed study on the abundance of aerobic anoxygenic phototrophic
bacteria and bacterioplankton, hydrochemistry and taxonomy of bacterioplankton in
the Maocun watershed, Southwest China, an area with karst geological background.
Our results revealed that bacteria are the important contributors to total
organic carbon source/sequestration in the groundwater-surface water of this
area. The aerobic anoxygenic phototrophic bacteria, including beta
Proteobacteria, also appear in the studied water system. In addition to that, the
genus Polynucleobacter of the phototropic beta-Proteobacteria shows a close link
with those sampling sites by presenting bacterial origin organic carbon on CCA
biplot and is found to be positively correlated with total nitrogen, dissolved
oxygen and pH (r = 0.860, 0.747 and 0.813, respectively) in the Maocun watershed.
The results suggest that Polynucleobacter might be involved in the production of
organic carbon and might act as the negative feedback on global warming.
PMID- 28498942
TI - Effect of vitamin D on all-cause mortality in heart failure (EVITA): a 3-year
randomized clinical trial with 4000 IU vitamin D daily.
AB - Aims: Circulating 25-hydroxyvitamin D (25OHD) levels <75 nmol/L are associated
with a nonlinear increase in mortality risk. Such 25OHD levels are common in
heart failure (HF). We therefore examined whether oral vitamin D supplementation
reduces mortality in patients with advanced HF. Methods and results: Four hundred
HF patients with 25OHD levels <75 nmol/L were randomized to receive 4000 IU
vitamin D daily or matching placebo for 3 years. Primary endpoint was all-cause
mortality. Key secondary outcome measures included hospitalization,
resuscitation, mechanical circulatory support (MCS) implant, high urgent listing
for heart transplantation, heart transplantation, and hypercalcaemia. Initial
25OHD levels were on average <40 nmol/L, remained around 40 nmol/L in patients
assigned to placebo and plateaued around 100 nmol/L in patients assigned to
vitamin D. Mortality was not different in patients receiving vitamin D (19.6%; n
= 39) or placebo (17.9%; n = 36) with a hazard ratio (HR) of 1.09 [95% confidence
interval (CI): 0.69-1.71; P = 0.726]. The need for MCS implant was however
greater in patients assigned to vitamin D (15.4%, n = 28) vs. placebo [9.0%, n =
15; HR: 1.96 (95% CI: 1.04-3.66); P = 0.031]. Other secondary clinical endpoints
were similar between groups. The incidence of hypercalcaemia was 6.2% (n = 10)
and 3.1% (n = 5) in patients receiving vitamin D or placebo (P = 0.192).
Conclusion: A daily vitamin D dose of 4000 IU did not reduce mortality in
patients with advanced HF but was associated with a greater need for MCS
implants. Data indicate caution regarding long-term supplementation with
moderately high vitamin D doses. Trial Registration Information:
clinicaltrials.gov Idenitfier: NCT01326650.
PMID- 28498944
TI - Assessment of standard laboratory tests and rotational thromboelastometry for the
prediction of postoperative bleeding in liver transplantation.
AB - Background: Perioperative bleeding remains a major challenge in liver
transplantation. We aimed to compare standard laboratory tests with
thromboelastometry (ROTEM (r) ) with regard to their ability to predict
postoperative non-surgical bleeding. Methods: Data from 243 adult liver
transplant recipients from January 2012 to May 2014 were evaluated
retrospectively. Upon admission to the intensive care unit, coagulation status
was assessed using standard laboratory tests [prothrombin time (PT), activated
partial thromboplastin time (aPTT), fibrinogen concentration, and platelet count]
and ROTEM (r) whole blood coagulation assays. Bleeding was defined as transfusion
of >= 3 units of red blood cells or reoperation for non-surgical bleeding within
48 h after transplantation. Coagulation test results were analysed using receiver
operating characteristics (ROC) in order to identify variables predictive of
postoperative bleeding. Coagulation management was based on ROTEM (r) -guided
factor concentrate treatment. Results: The overall incidence of bleeding was
12.3% ( n =30). Twenty-three (9.5%) patients underwent reoperation and seven
(2.9%) received >=3 units of red blood cells and non-operative management.
Standard laboratory tests predictive of postoperative bleeding were aPTT and PT
[area under the ROC curve (AUC) 0.688 and 0.623, respectively]. Tests predictive
of bleeding with ROTEM (r) were CT EXTEM , CFT INTEM , A10 FIBTEM , and MCF
FIBTEM , with AUCs of 0.682, 0.615, 0.615, and 0.611, respectively. Fibrinogen
concentration, platelet count, and other ROTEM (r) variables failed to
demonstrate predictive value for postoperative bleeding (AUC <0.6). Dialysis
dependent kidney failure, 30 day mortality, and median model for endstage liver
disease score were all significantly higher in bleeding patients. Conclusions:
Although both postoperative standard laboratory tests and ROTEM (r) assays could
identify patients at risk for postoperative bleeding, ROTEM (r) assays
demonstrated a greater predictive value for impaired fibrinogen polymerization
related coagulopathy.
PMID- 28498943
TI - Mycobacterium tuberculosis Whole Genome Sequences From Southern India Suggest
Novel Resistance Mechanisms and the Need for Region-Specific Diagnostics.
AB - Background.: India is home to 25% of all tuberculosis cases and the second
highest number of multidrug resistant cases worldwide. However, little is known
about the genetic diversity and resistance determinants of Indian Mycobacterium
tuberculosis, particularly for the primary lineages found in India, lineages 1
and 3. Methods.: We whole genome sequenced 223 randomly selected M. tuberculosis
strains from 196 patients within the Tiruvallur and Madurai districts of Tamil
Nadu in Southern India. Using comparative genomics, we examined genetic
diversity, transmission patterns, and evolution of resistance. Results.: Genomic
analyses revealed (11) prevalence of strains from lineages 1 and 3, (11) recent
transmission of strains among patients from the same treatment centers, (11)
emergence of drug resistance within patients over time, (11) resistance gained in
an order typical of strains from different lineages and geographies, (11)
underperformance of known resistance-conferring mutations to explain phenotypic
resistance in Indian strains relative to studies focused on other geographies,
and (11) the possibility that resistance arose through mutations not previously
implicated in resistance, or through infections with multiple strains that
confound genotype-based prediction of resistance. Conclusions.: In addition to
substantially expanding the genomic perspectives of lineages 1 and 3, sequencing
and analysis of M. tuberculosis whole genomes from Southern India highlight
challenges of infection control and rapid diagnosis of resistant tuberculosis
using current technologies. Further studies are needed to fully explore the
complement of diversity and resistance determinants within endemic M.
tuberculosis populations.
PMID- 28498945
TI - Conversion after off-pump coronary artery bypass grafting: where are the quality
markers?
PMID- 28498948
TI - Community composition and assembly processes of the free-living and particle
attached bacteria in Taihu Lake.
AB - Although previous studies have compared the diversity and community composition
of free-living (FL) and particle-attached (PA) bacterial groups in marine
ecosystems, few studies have focused on the FL and PA bacterial communities in
large and shallow eutrophic lakes. Furthermore, the assembly processes of the FL
and PA bacterial communities have not been investigated. To illustrate the
differences between PA (>=5.0 MUm) and FL (0.22-5.0 MUm) bacterial communities,
samples were collected from 13 different sites in Taihu Lake, China. A higher
diversity of the PA bacterial group than that of the FL group was observed, and
significant differences in bacterial community composition between FL and PA
groups were found (analysis of similarity, R = 0.2425, P < 0.001). Moreover, the
two groups exhibited different relationships with environmental factors and
geographic distance. Environmental factors played more important roles in
affecting the FL bacterial community. A deterministic process was found as the
primary factor driving the community of FL bacteria in Taihu Lake. However, the
PA bacterial group was characterized by insignificant results of partial Mantel
tests, which indicated that the community assembly was controlled by unknown
processes.
PMID- 28498947
TI - Aminobacter sp. MSH1 invades sand filter community biofilms while retaining 2,6
dichlorobenzamide degradation functionality under C- and N-limiting conditions.
AB - Aminobacter sp. MSH1 is of interest for bioaugmentation of biofiltration units in
drinking water treatment plants (DWTPs) due to its ability to degrade the
groundwater micropollutant 2,6-dichlorobenzamide (BAM). Using a continuous flow
chamber biofilm model, MSH1 was previously shown to colonize surfaces and degrade
BAM at trace concentrations as low as 1 MUg/L under the oligotrophic conditions
found in DWTPs. In DWTP filtration units, MSH1 has to compete with the resident
biofilm microbiota for space and nutrients. Using the same model, we examined how
a sand filter community (SFC) affects MSH1's BAM-degrading activity and biofilm
formation under C- and N-limiting conditions when fed with trace concentrations
of BAM. MSH1 was inoculated simultaneously with the SFC (co-colonization mode) or
after the SFC formed a biofilm (invasion mode). MSH1 successfully established in
the SFC biofilm showing growth and activity. In co-colonization mode, MSH1
decreased in number in the presence of the SFC and formed isolated colonies,
while specific BAM-degradation activity increased. In the invasion mode, MSH1
also decreased in numbers in the presence of the SFC but formed mixed colonies,
while specific BAM degradation was unaffected. Our results show that MSH1 invades
and performs successfully in an SFC biofilm under the oligotrophic conditions of
DWTPs.
PMID- 28498946
TI - Overexpression of Rev1 promotes the development of carcinogen-induced intestinal
adenomas via accumulation of point mutation and suppression of apoptosis
proportionally to the Rev1 expression level.
AB - Cancer development often involves mutagenic replication of damaged DNA by the
error-prone translesion synthesis (TLS) pathway. Aberrant activation of this
pathway plays a role in tumorigenesis by promoting genetic mutations. Rev1
controls the function of the TLS pathway, and Rev1 expression levels are
associated with DNA damage induced cytotoxicity and mutagenicity. However, it
remains unclear whether deregulated Rev1 expression triggers or promotes
tumorigenesis in vivo. In this study, we generated a novel Rev1-overexpressing
transgenic (Tg) mouse and characterized its susceptibility to tumorigenesis.
Using a small intestinal tumor model induced by N-methyl-N-nitrosourea (MNU), we
found that transgenic expression of Rev1 accelerated intestinal adenoma
development in proportion to the Rev1 expression level; however, overexpression
of Rev1 alone did not cause spontaneous development of intestinal adenomas. In
Rev1 Tg mice, MNU-induced mutagenesis was elevated, whereas apoptosis was
suppressed. The effects of hREV1 expression levels on the cytotoxicity and
mutagenicity of MNU were confirmed in the human cancer cell line HT1080. These
data indicate that dysregulation of cellular Rev1 levels leads to the
accumulation of mutations and suppression of cell death, which accelerates the
tumorigenic activities of DNA-damaging agents.
PMID- 28498949
TI - Proteolytic cleavage is required for functional neuroligin 2 maturation and
trafficking in Drosophila.
AB - Neuroligins (Nlgs) are transmembrane cell adhesion molecules playing essential
roles in synapse development and function. Genetic mutations in neuroligin genes
have been linked with some neurodevelopmental disorders such as autism. These
mutated Nlgs are mostly retained in the endoplasmic reticulum (ER). However, the
mechanisms underlying normal Nlg maturation and trafficking have remained largely
unknown. Here, we found that Drosophila neuroligin 2 (DNlg2) undergoes
proteolytic cleavage in the ER in a variety of Drosophila tissues throughout
developmental stages. A region encompassing Y642-T698 is required for this
process. The immature non-cleavable DNlg2 is retained in the ER and non
functional. The C-terminal fragment of DNlg2 instead of the full-length or non
cleavable DNlg2 is able to rescue neuromuscular junction defects and GluRIIB
reduction induced by dnlg2 deletion. Intriguingly, the autism-associated R598C
mutation in DNlg2 leads to similar marked defects in DNlg2 proteolytic process
and ER export, revealing a potential role of the improper Nlg cleavage in autism
pathogenesis. Collectively, our findings uncover a specific mechanism that
controls DNlg2 maturation and trafficking via proteolytic cleavage in the ER,
suggesting that the perturbed proteolytic cleavage of Nlgs likely contributes to
autism disorder.
PMID- 28498950
TI - IGESS: a statistical approach to integrating individual-level genotype data and
summary statistics in genome-wide association studies.
AB - Motivation: Results from genome-wide association studies (GWAS) suggest that a
complex phenotype is often affected by many variants with small effects, known as
'polygenicity'. Tens of thousands of samples are often required to ensure
statistical power of identifying these variants with small effects. However, it
is often the case that a research group can only get approval for the access to
individual-level genotype data with a limited sample size (e.g. a few hundreds or
thousands). Meanwhile, summary statistics generated using single-variant-based
analysis are becoming publicly available. The sample sizes associated with the
summary statistics datasets are usually quite large. How to make the most
efficient use of existing abundant data resources largely remains an open
question. Results: In this study, we propose a statistical approach, IGESS, to
increasing statistical power of identifying risk variants and improving accuracy
of risk prediction by i ntegrating individual level ge notype data and s ummary s
tatistics. An efficient algorithm based on variational inference is developed to
handle the genome-wide analysis. Through comprehensive simulation studies, we
demonstrated the advantages of IGESS over the methods which take either
individual-level data or summary statistics data as input. We applied IGESS to
perform integrative analysis of Crohns Disease from WTCCC and summary statistics
from other studies. IGESS was able to significantly increase the statistical
power of identifying risk variants and improve the risk prediction accuracy from
63.2% ( +/-0.4% ) to 69.4% ( +/-0.1% ) using about 240 000 variants. Availability
and implementation: The IGESS software is available at
https://github.com/daviddaigithub/IGESS . Contact: zbxu@xjtu.edu.cn or
xwan@comp.hkbu.edu.hk or eeyang@hkbu.edu.hk. Supplementary information:
Supplementary data are available at Bioinformatics online.
PMID- 28498951
TI - Single-Target and Multiplex Discrimination of Whiteflies (Hemiptera: Aleyrodidae)
Bemisia tabaci and Trialeurodes vaporariorum With Modified Priming
Oligonucleotide Thermodynamics.
AB - The whitefly species Bemisia tabaci (Gennadius) and Trialeurodes vaporariorum
(Westwood) are worldwide agricultural pests and virus vectors. Bemisia tabaci, in
particular, is often transported internationally via trade routes leading to
potential introductions of exotic whiteflies or plant viruses. Quick
identification of agriculturally important whiteflies can facilitate
interventions that prevent these cross-border introductions. Polymerase chain
reaction (PCR) primers were designed to amplify the mitochondrial cytochrome
oxidase I gene (mtCOI) sequence of members of the B. tabaci complex, MEAM1, MED,
and NW, and T. vaporariorum. Primers incorporated an A/T-rich overhang sequence
at the 5' terminus (5' flap) to test for increased primer sensitivity and assay
efficiency. Single-target and multiplex endpoint PCR assays with the eight primer
sets were performed using genomic DNA template extracted from individual adult
whiteflies. Resultant PCR amplicons obtained for B. tabaci MEAM1, MED, and NW,
and T. vaporariorum primers with the 5' flap were 559-, 717-, 353-, and 258-bp,
respectively, and without the 5' flap were 550-, 712-, 329-, and 252-bp in
length, respectively. In single-target and multiplex reactions, specific
amplification was achieved using both the unmodified and 5' flap-modified
primers. Sequencing and phylogenetic analysis confirmed primer-target
amplification specificity. Using these primer sets in single-target or multiplex
PCR allows for quick discrimination and specific identification of B. tabaci
complex members and T. vaporariorum, and the addition of 5'A/T-rich overhang
sequences increases the sensitivity and amplification of some primer sets.
PMID- 28498952
TI - Virtual virus, a semester-long interdisciplinary project on the crossroads of
creativity and knowledge integration.
AB - Virtual virus is a semester-long interdisciplinary project offered as part of
upper level elective course in virology. Students are challenged to apply key
concepts from multiple biological sub-disciplines to 'synthesize' a plausible
virtual virus. The project is executed as a scaffolded series of hands-on
sessions and mini-projects that are integrated into continuous story leading to
mock conference presentation and comprehensive report modeling article
publication. It complements classroom instruction helping students to meet
overarching learning targets traditionally associated undergraduate virology
courses such as viral structure and function, mode of viral propagation and flow
of genetic information and virus/host interactions on the cellular and organismal
level. Formal instructor and informal peer feedback were used as tools to prompt
reflection and guide revisions of the final report. Student learning gains and
attitudes toward the approach were studied by evaluating project work product and
end of the semester survey. Outcome analysis demonstrated that students exit the
course with elaborated conceptual understanding of viruses and ownership of their
work. The project can be viewed as an approach to model the process of scientific
discovery in fast-forward mode by combining active learning, creativity and
problem solving to assemble and communicate a virtual virus story.
PMID- 28498955
TI - Transcatheter transapical left ventricle remodelling in ischaemic cardiomyopathy
with apical aneurysm using 3rd generation 3D cardiac computed tomography fusion
imaging.
PMID- 28498953
TI - Pathological Role of Anti-CD4 Antibodies in HIV-Infected Immunologic
Nonresponders Receiving Virus-Suppressive Antiretroviral Therapy.
AB - Increased mortality and morbidity occur among human immunodeficiency virus (HIV)
infected patients in whom CD4+ T-cell counts do not increase despite viral
suppression with antiretroviral therapy (ART). Here we identified an underlying
mechanism. Significantly elevated plasma levels of anti-CD4 immunoglobulin G
(IgG) were found in HIV-positive immunologic nonresponders (ie, HIV-positive
individuals with CD4+ T-cell counts of <=350 cells/MUL), compared with levels in
HIV-positive immunologic responders (ie, HIV-positive individuals with CD4+ T
cell counts of >=500 cells/MUL) and healthy controls. Higher plasma level of anti
CD4 IgG correlated with blunted CD4+ T-cell recovery. Furthermore, purified anti
CD4 IgG from HIV-positive immunologic nonresponders induced natural killer (NK)
cell-dependent CD4+ T-cell cytolysis and apoptosis through antibody-dependent
cell-mediated cytotoxicity (ADCC) in vitro. We also found that anti-CD4 IgG
mediated ADCC exerts greater apoptosis of naive CD4+ T cells relative to memory
CD4+ T cells. Consistently, increased frequencies of CD107a+ NK cells and
profound decreases of naive CD4+ T cells were observed in immunologic
nonresponders as compared to responders and healthy controls ex vivo. These data
indicate that autoreactive anti-CD4 IgG may play an important role in blunted
CD4+ T-cell reconstitution despite effective ART.
PMID- 28498954
TI - Cognitive Impairment in Bipolar Disorder: Treatment and Prevention Strategies.
AB - Over the last decade, there has been a growing appreciation of the importance of
identifying and treating cognitive impairment associated with bipolar disorder,
since it persists in remission periods. Evidence indicates that neurocognitive
dysfunction may significantly influence patients' psychosocial outcomes. An ever
increasing body of research seeks to achieve a better understanding of potential
moderators contributing to cognitive impairment in bipolar disorder in order to
develop prevention strategies and effective treatments. This review provides an
overview of the available data from studies examining treatments for cognitive
dysfunction in bipolar disorder as well as potential novel treatments, from both
pharmacological and psychological perspectives. All these data encourage the
development of further studies to find effective strategies to prevent and treat
cognitive impairment associated with bipolar disorder. These efforts may
ultimately lead to an improvement of psychosocial functioning in these patients.
PMID- 28498957
TI - Global Tactile Coding in Rat Barrel Cortex in the Absence of Local Cues.
AB - Although whisker-related perception is based predominantly on local, near
instantaneous coding, global, intensive coding, which integrates the vibrotactile
signal over time, has also been shown to play a role given appropriate behavioral
conditions. Here, we study global coding in isolation by studying head-fixed rats
that identified pulsatile stimuli differing in pulse frequency but not in pulse
waveforms, thus abolishing perception based on local coding. We quantified time
locking and spike counts as likely variables underpinning the 2 coding schemes.
Both neurometric variables contained substantial stimulus information, carried
even by spikes of single barrel cortex neurons. To elucidate which type of
information is actually used by the rats, we systematically compared psychometric
with neurometric sensitivity based on the 2 coding schemes. Neurometric
performance was calculated by using a population-encoding model incorporating the
properties of our recorded neuron sample. We found that sensitivity calculated
from spike counts sampled over long periods (>1 s) matched the performance of
rats better than the one carried by spikes time-locked to the stimulus. We
conclude that spike counts are more relevant to tactile perception when
instantaneous kinematic parameters are not available.
PMID- 28498956
TI - The Lateral Temporal Lobe in Early Human Life.
AB - Abnormalities of lateral temporal lobe development are associated with a spectrum
of genetic and environmental pathologic processes, but more normative data are
needed for a better understanding of gyrification in this brain region. Here, we
begin to establish guidelines for the analysis of the lateral temporal lobe in
humans in early life. We present quantitative methods for measuring gyrification
at autopsy using photographs of the gross brain and simple computer-based
quantitative tools in a cohort of 28 brains ranging in age from 27 to 70
postconceptional weeks (end of infancy). We provide normative ranges for
different indices of gyrification and identify a constellation of qualitative
features that should also be considered in these analyses. The ratio of the
temporal area to the whole brain area increased dramatically in the second half
of gestation, but then decelerated after birth before increasing linearly around
50 postconceptional weeks. Tertiary gyrification continued beyond birth in a
linear process through infancy with considerable variation in patterns. Analysis
of 2 brains with gyral disorders of the lateral temporal lobe demonstrated proof
of-principle that the proposed methods are of diagnostic value. These guidelines
are proposed for assessments of temporal lobe pathology in pediatric brains in
early life.
PMID- 28498958
TI - compleXView: a server for the interpretation of protein abundance and
connectivity information to identify protein complexes.
AB - The molecular understanding of cellular processes requires the identification and
characterization of the involved protein complexes. Affinity-purification and
mass spectrometric analysis (AP-MS) are performed on a routine basis to detect
proteins assembled in complexes. In particular, protein abundances obtained by
quantitative mass spectrometry and direct protein contacts detected by
crosslinking and mass spectrometry (XL-MS) provide complementary datasets for
revealing the composition, topology and interactions of modules in a protein
network. Here, we aim to combine quantitative and connectivity information by a
webserver tool in order to infer protein complexes. In a first step, modeling
protein abundances and functional annotations from Gene Ontology (GO) results in
a network which, in a second step, is integrated with connectivity data from XL
MS analysis in order to complement and validate the protein complexes in the
network. The output of our integrative approach is a quantitative protein
interaction map which is supplemented with topological information of the
detected protein complexes. compleXView is built up by two independent modules
which are dedicated to the analysis of label-free AP-MS data and to the
visualization of the detected complexes in a network together with crosslink
derived distance restraints. compleXView is available to all users without login
requirements at http://xvis.genzentrum.lmu.de/compleXView.
PMID- 28498959
TI - Pan-American Similarities in Genetic Structures of Helicoverpa armigera and
Helicoverpa zea (Lepidoptera: Noctuidae) With Implications for Hybridization.
AB - The genus Helicoverpa (Lepidoptera: Noctuidae) includes phytophagous and
polyphagous agricultural insect pests. In the Americas, a native pest,
Helicoverpa zea (Boddie), and an invasive pest, Helicoverpa armigera (Hubner),
are causing severe damage in vegetable and agronomic crops. The population
structure of both species in South America is poorly understood, and the
phylogenetic relatedness of H. armigera and H. zea suggests natural interspecific
gene flow between these species. Using microsatellite loci, we investigated: 1)
the genetic diversity and gene flow of H. armigera specimens from Brazil; 2) the
genetic diversity and gene flow between H. zea specimens from Brazil and the
United States; and 3) the possibility of interspecific gene flow and the
frequency of putative hybrids in Brazil. We detected high intraspecific gene flow
among populations collected in the same country. However, there is a geographic
limit to gene flow among H. zea individuals from South and North America.
Pairwise Fst and private alleles showed that H. armigera is more similar to H.
zea from Brazil than H. zea from the United States. A comparative STRUCTURE
analysis suggests natural hybridization between H. armigera and H. zea in Brazil.
High gene flow and natural hybridization are key traits to population adaptation
in new and disturbed environments, which can influence the management of these
pests in the American continent.
PMID- 28498960
TI - Which is worse? Comparison of ART outcome between women with primary or recurrent
endometriomas.
AB - STUDY QUESTION: Are live birth rates (LBR) different after ART cycles between
women with primary or recurrent endometrioma? SUMMARY ANSWER: Women with
recurrent endometrioma have similar LBR as compared to patients with primary
endometrioma. WHAT IS ALREADY KNOWN: Recurrence rate can be as high as 29% after
endometrioma excision. Prior studies on management of endometrioma before ART
involve primary endometriomas. There is limited information regarding the
prognosis of women with recurrent endometriomas. STUDY DESIGN, SIZE, DURATION: A
multicenter retrospective cohort study, including 76 women with primary and 82
women with recurrent endometriomas treated at the participating centers over a 6
year period. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with endometrioma
who underwent ART at three academic ART centers. Couples with another indication
for ART were excluded. MAIN RESULTS AND THE ROLE OF CHANCE: Female age, median
number of prior failed ART cycles, proportion of patients with bilateral
endometrioma (28 versus 28.9%), ovarian stimulation protocols, and total
gonadotropin consumption were similar between the study groups. Numbers of
metaphase two oocytes (5 versus 6), number of embryos transferred, and the
proportion of patients undergoing blastocyst transfer were similar across the
study groups. Clinical pregnancy rates (36.6 versus 34.2%, absolute difference
2.4%, 95% CI: -12.5 to 17.3%, P = 0.83) and LBR (35.4 versus 30.3%, absolute
difference 5.1%, 95% CI: -9.5 to 19.7%, P = 0.51) per started cycle in recurrent
and primary endometrioma were similar. Comparable success rates were also
confirmed with logistic regression analysis (OR: 1.14, 95% CI: 0.78-0.57, P =
2.3). LIMITATIONS, REASONS FOR CAUTION: The retrospective design has inherent
limitations. Some women with severely decreased ovarian reserve after primary
endometrioma excision may not have pursued further treatment. WIDER IMPLICATIONS
OF THE FINDINGS: The management of endometrioma prior to ART is controversial but
a different management strategy is not required for recurrent endometriomas.
Since recurrent endometriomas do not have a worse impact on ART outcome than
primary endometriomas, and repeat surgery has a higher risk for complications,
conservative management without surgery can be justified. STUDY FUNDING/COMPETING
INTEREST(S): No funding or competing interests to declare. TRIAL REGISTRATION
NUMBER: None.
PMID- 28498961
TI - Range-Wide Snow Leopard Phylogeography Supports Three Subspecies.
AB - The snow leopard, Panthera uncia, is an elusive high-altitude specialist that
inhabits vast, inaccessible habitat across Asia. We conducted the first range
wide genetic assessment of snow leopards based on noninvasive scat surveys.
Thirty-three microsatellites were genotyped and a total of 683 bp of
mitochondrial DNA sequenced in 70 individuals. Snow leopards exhibited low
genetic diversity at microsatellites (AN = 5.8, HO = 0.433, HE = 0.568),
virtually no mtDNA variation, and underwent a bottleneck in the Holocene (~8000
years ago) coinciding with increased temperatures, precipitation, and upward
treeline shift in the Tibetan Plateau. Multiple analyses supported 3 primary
genetic clusters: (1) Northern (the Altai region), (2) Central (core Himalaya and
Tibetan Plateau), and (3) Western (Tian Shan, Pamir, trans-Himalaya regions).
Accordingly, we recognize 3 subspecies, Panthera uncia irbis (Northern group),
Panthera uncia uncia (Western group), and Panthera uncia uncioides (Central
group) based upon genetic distinctness, low levels of admixture, unambiguous
population assignment, and geographic separation. The patterns of variation were
consistent with desert-basin "barrier effects" of the Gobi isolating the northern
subspecies (Mongolia), and the trans-Himalaya dividing the central (Qinghai,
Tibet, Bhutan, and Nepal) and western subspecies (India, Pakistan, Tajikistan,
and Kyrgyzstan). Hierarchical Bayesian clustering analysis revealed additional
subdivision into a minimum of 6 proposed management units: western Mongolia,
southern Mongolia, Tian Shan, Pamir-Himalaya, Tibet-Himalaya, and Qinghai, with
spatial autocorrelation suggesting potential connectivity by dispersing
individuals up to ~400 km. We provide a foundation for global conservation of
snow leopard subspecies, and set the stage for in-depth landscape genetics and
genomic studies.
PMID- 28498962
TI - An iterative glycosyltransferase EntS catalyzes transfer and extension of O- and
S-linked monosaccharide in enterocin 96.
AB - Glycosyltransferases are essential tools for in vitro-glycoengineering. Bacteria
harbor an unexplored variety of protein glycosyltransferases. Here, we describe a
peptide glycosyltransferase (EntS) encoded by ORF0417 of Enterococcus faecalis
TX0104. EntS di-glycosylates linear peptide of enterocin 96- a known
antibacterial, in vitro. It is capable of transferring as well as extending the
glycan onto the peptide in an iterative sequential dissociative manner. It can
catalyze multiple linkages: Glc/Gal(-O)Ser/Thr, Glc/Gal(-S)Cys and
Glc/Gal(beta)Glc/Gal(-O/S)Ser/Thr/Cys, in one pot. Using EntS generated
glycovariants of enterocin 96 peptide, size and identity of the glycan are found
to influence bioactivity of the peptide. The study identifies EntS as an enzyme
worth pursuing, for in vitro peptide glycoengineering.
PMID- 28498963
TI - Hypertension in kidney transplantation is associated with an early renal nerve
sprouting.
AB - Background.: Normalization of arterial pressure occurs in just a few patients
with hypertensive chronic kidney disease undergoing kidney transplantation.
Hypertension in kidney transplant recipients may be related to multiple factors.
We aimed to assess whether hypertension in kidney-transplanted patients may be
linked to reinnervation of renal arteries of the transplanted kidney. Methods.:
We investigated renal arteries innervation from native and transplanted kidneys
in three patients 5 months, 2 years and 11 years after transplantation,
respectively. Four transplanted kidneys from non-hypertensive patients on
immunosuppressive treatment without evidence of hypertensive arteriolar damage
were used as controls. Results: . Evidence of nerve sprouting was observed as
early as 5 months following transplantation, probably originated from ganglions
of recipient patient located near the arterial anastomosis and was associated
with mild hypertensive arteriolar damage. Regeneration of periadventitial nerves
was already complete 2 years after transplantation. Nerve density tended to reach
values observed in native kidney arteries and was associated with hypertension
related arteriolar lesions in transplanted kidneys. Control kidneys, albeit on an
immunosuppressive regimen, presented only a modest regeneration of sympathetic
nerves. Conclusions: . Our results suggest that the considerable increase in
sympathetic nerves, as found in patients with severe arterial damage, may be
correlated to hypertension rather than to immunosuppressive therapy, thus
providing a morphological basis for hypertension recurrence despite renal
denervation.
PMID- 28498964
TI - Superior Neuronal Detection of Snakes and Conspecific Faces in the Macaque Medial
Prefrontal Cortex.
AB - Snakes and conspecific faces are quickly and efficiently detected in primates.
Because the medial prefrontal cortex (mPFC) has been implicated in attentional
allocation to biologically relevant stimuli, we hypothesized that it might also
be highly responsive to snakes and conspecific faces. In this study, neuronal
responses in the monkey mPFC were recorded, while monkeys discriminated 8
categories of visual stimuli. Here, we show that the monkey mPFC neuronal
responses to snakes and conspecific faces were unique. First, the ratios of the
neurons that responded strongly to snakes and monkey faces were greater than
those of the neurons that responded strongly to the other stimuli. Second, mPFC
neurons responded stronger and faster to snakes and monkey faces than the other
categories of stimuli. Third, neuronal responses to snakes were unaffected by low
pass filtering of the images. Finally, activity patterns of responsive mPFC
neurons discriminated snakes from the other stimuli in the second 50 ms period
and monkey faces in the third period after stimulus onset. These response
features indicate that the mPFC processes fast and coarse visual information of
snakes and monkey faces, and support the hypothesis that snakes and social
environments have shaped the primate visual system over evolutionary time.
PMID- 28498965
TI - Detection of Zika virus in a traveller from Vietnam to Japan.
AB - We report an imported case of Zika fever in a traveller from Vietnam. Zika virus
(ZIKV) is currently widespread in Vietnam. Ongoing transmission of ZIKV has been
reported in Southeast Asia, and with frequent travel between neighbouring
regions, careful surveillance for imported cases is needed.
PMID- 28498966
TI - GenProBiS: web server for mapping of sequence variants to protein binding sites.
AB - Discovery of potentially deleterious sequence variants is important and has wide
implications for research and generation of new hypotheses in human and
veterinary medicine, and drug discovery. The GenProBiS web server maps sequence
variants to protein structures from the Protein Data Bank (PDB), and further to
protein-protein, protein-nucleic acid, protein-compound, and protein-metal ion
binding sites. The concept of a protein-compound binding site is understood in
the broadest sense, which includes glycosylation and other post-translational
modification sites. Binding sites were defined by local structural comparisons of
whole protein structures using the Protein Binding Sites (ProBiS) algorithm and
transposition of ligands from the similar binding sites found to the query
protein using the ProBiS-ligands approach with new improvements introduced in
GenProBiS. Binding site surfaces were generated as three-dimensional grids
encompassing the space occupied by predicted ligands. The server allows intuitive
visual exploration of comprehensively mapped variants, such as human somatic mis
sense mutations related to cancer and non-synonymous single nucleotide
polymorphisms from 21 species, within the predicted binding sites regions for
about 80 000 PDB protein structures using fast WebGL graphics. The GenProBiS web
server is open and free to all users at http://genprobis.insilab.org.
PMID- 28498967
TI - Surgical resection after neoadjuvant chemoradiation for oesophageal
adenocarcinoma: what is the optimal timing?
AB - OBJECTIVES: The purpose of this study was to determine the optimal timing of
surgical resection of oesophageal adenocarcinoma following neoadjuvant
chemoradiotherapy (nCRT). METHODS: nCRT before resection of oesophageal
adenocarcinoma yields improved overall and progression-free survival. Despite the
wide acceptance of tri-modal therapy, the optimal timing of surgical resection
after nCRT is not well defined and existing studies are limited. Adults with
Stage II/III oesophageal adenocarcinoma undergoing nCRT before surgery were
identified from the National Cancer Database. Multivariable analysis using
restricted cubic splines was used to identify an inflection point in clinical
outcomes as a function of time between nCRT and surgery, dividing the cohort into
short- and long-interval treatment groups, which were then compared. Adjusted
rates of survival and margin status were compared between groups using
multivariable analysis. RESULTS: Among 2444 patients, restricted cubic splines
identified an inflection point at 56 days, dividing our cohort into 1533 short
interval and 911 long-interval patients. Long-interval patients had a higher
adjusted incidence of pathologic downstaging (odds ratio 1.38, confidence
interval 1.02-1.85, P = 0.04) but no difference in margin positivity compared
with short-interval patients (odds ratio 0.91, confidence interval 0.56-1.47, P =
0.69). Worse overall survival was noted in the long-interval subgroup (hazard
ratio 1.44, confidence interval 1.22-1.71, P < 0.001), but 30-day postoperative
mortality was not statistically different (odds ratio 1.56, confidence interval
0.9-2.72, P = 0.12). CONCLUSIONS: Restricted cubic splines provides an objective
mechanism to more accurately delineate optimum timing between nCRT and surgical
resection. A time interval of 56 days represents an interval where increased
pathologic downstaging is balanced by decreased overall survival.
PMID- 28498968
TI - The involvement of alcohol in hospital-treated self-harm and associated factors:
findings from two national registries.
AB - Background: Alcohol is often involved in hospital-treated self-harm. Therefore it
is important to establish the role of alcohol in self-harm as well as to identify
associated factors, in order to best inform service provision. Methods: Data on
self-harm presentations to hospital emergency departments in Ireland and Northern
Ireland from April 2012 to December 2013 were analysed. We calculated the
prevalence of alcohol consumption in self-harm. Using Poisson regression models,
we identified the factors associated with having consumed alcohol at the time of
a self-harm act. Results: Alcohol was present in 43% of all self-harm acts, and
more common in Northern Ireland (50 versus 37%). The factors associated with
alcohol being involved were being male, aged between 25 and 64 years, and having
engaged in a drug overdose or attempted drowning. Presentations made out-of-hours
were more likely to have alcohol present and this was more pronounced for
females. Patients with alcohol on board were also more likely to leave without
having been seen by a clinician. Conclusions: This study has highlighted the
prevalence of alcohol in self-harm presentations, and has identified factors
associated with presentations involving alcohol. Appropriate out-of-hours
services in emergency departments for self-harm presentations could reduce the
proportion of presentations leaving without being seen by a clinician and
facilitate improved outcomes for patients.
PMID- 28498969
TI - DEVELOPMENT OF ISOTOPICALLY ENRICHED BORON-DOPED ALUMINA DOSIMETER FOR THERMAL
NEUTRONS.
AB - A novel optically stimulated luminescence (OSL) detector containing isotopically
enriched boron was developed for thermal neutron dosimetry. Alumina containing
isotopically enriched boron (Al2O3:B) was synthesised by the sol-gel method. The
Al2O3:B was annealed up to ~1800 K. For X-ray diffractometer (XRD) analysis, the
diffraction pattern of the Al2O3:B had reflex peaks corresponding to alpha-Al2O3.
The sensitivity of Al2O3:B to photons was slightly 2% of that of a commercial
Al2O3:C. The Al2O3:B detector had satisfactory linearity in X-ray dose
measurement. A thermal neutron field was constructed using a 241Am-Be neutron
source and graphite blocks. A pair of Al2O3:10B and Al2O3:11B detectors were set
in the thermal neutron field. The response of Al2O3:10B was larger than that of
Al2O3:11B owing to the 10B(n,alpha)7Li reactions. The sensitivity of Al2O3:10B to
thermal neutrons was estimated to be two orders less than the photon sensitivity.
Therefore, the pair of Al2O3:10B and Al2O3:11B detectors were useful for thermal
neutron dosimetry.
PMID- 28498970
TI - Results of a multimodal approach for the management of aortic coarctation and its
complications in adults.
AB - OBJECTIVES: We aimed to assess the results of various tailored management
strategies for adults with coarctation in our centre. METHODS: We reviewed all
adults patients treated for aortic caorctation between January 2000 and December
2015 in our institution. The primary end point was a composite of death,
perioperative stroke, paraplegia, need for unplanned reoperation or occurrence of
pseudoaneurysm during the follow-up. The mean follow-up was 82 +/- 5 months.
RESULTS: Sixty-three adults were treated for a native coarctation (n = 34), a
recurrent coarctation (n = 14) or aneurysmal complication (n = 15). Mean age of
the patients was 42 +/- 1.7 years. All but 1 patient with native coarctation
(33/34, 97%) and recurrent coarctation (13/14, 93%) underwent endovascular repair
and 10 (67%) patients with aneurysmal complications were treated surgically.
Freedom from the primary composite end point was 94, 84 and 81% at 1, 5 and 10
years, respectively, without difference between the 3 indication groups (P =
0.96). CONCLUSIONS: A tailored management strategy is necessary to provide good
results for the treatment of adults with aortic coarctation. Thus, centres that
are involved in the care of this complex pathology should be able to propose a
multimodal approach, either endovascular or surgical depending on patient's
characteristics and anatomic features.
PMID- 28498972
TI - Development of a Combined In Vitro Physiologically Based Kinetic (PBK) and Monte
Carlo Modelling Approach to Predict Interindividual Human Variation in Phenol
Induced Developmental Toxicity.
AB - With our recently developed in vitro physiologically based kinetic (PBK)
modelling approach, we could extrapolate in vitro toxicity data to human toxicity
values applying PBK-based reverse dosimetry. Ideally information on kinetic
differences among human individuals within a population should be considered. In
the present study, we demonstrated a modelling approach that integrated in vitro
toxicity data, PBK modelling and Monte Carlo simulations to obtain insight in
interindividual human kinetic variation and derive chemical specific adjustment
factors (CSAFs) for phenol-induced developmental toxicity. The present study
revealed that UGT1A6 is the primary enzyme responsible for the glucuronidation of
phenol in humans followed by UGT1A9. Monte Carlo simulations were performed
taking into account interindividual variation in glucuronidation by these
specific UGTs and in the oral absorption coefficient. Linking Monte Carlo
simulations with PBK modelling, population variability in the maximum plasma
concentration of phenol for the human population could be predicted. This
approach provided a CSAF for interindividual variation of 2.0 which covers the
99th percentile of the population, which is lower than the default safety factor
of 3.16 for interindividual human kinetic differences. Dividing the dose-response
curve data obtained with in vitro PBK-based reverse dosimetry, with the CSAF
provided a dose-response curve that reflects the consequences of the
interindividual variability in phenol kinetics for the developmental toxicity of
phenol. The strength of the presented approach is that it provides insight in the
effect of interindividual variation in kinetics for phenol-induced developmental
toxicity, based on only in vitro and in silico testing.
PMID- 28498971
TI - Deletion of RhoA in Progesterone Receptor-Expressing Cells Leads to Luteal
Insufficiency and Infertility in Female Mice.
AB - Ras homolog gene family, member A (RhoA) is widely expressed throughout the
female reproductive system. To assess its role in progesterone receptor
expressing cells, we generated RhoA conditional knockout mice RhoAd/d (RhoAf/f
Pgr-Cre+/-). RhoAd/d female mice had comparable mating activity, serum
luteinizing hormone, prolactin, and estradiol levels and ovulation with control
but were infertile with progesterone insufficiency, indicating impaired
steroidogenesis in RhoAd/d corpus luteum (CL). RhoA was highly expressed in wild
type luteal cells and conditionally deleted in RhoAd/d CL. Gestation day 3.5
(D3.5) RhoAd/d ovaries had reduced numbers of CL, less defined corpus luteal cord
formation, and disorganized CL collagen IV staining. RhoAd/d CL had lipid droplet
and free cholesterol accumulation, indicating the availability of cholesterol for
steroidogenesis, but disorganized beta-actin and vimentin staining, indicating
disrupted cytoskeleton integrity. Cytoskeleton is important for cytoplasmic
cholesterol movement to mitochondria and for regulating mitochondria.
Dramatically reduced expression of mitochondrial markers heat shock protein 60
(HSP60), voltage-dependent anion channel, and StAR was detected in RhoAd/d CL.
StAR carries out the rate-limiting step of steroidogenesis. StAR messenger RNA
expression was reduced in RU486-treated D3.5 wild-type CL and tended to be
induced in progesterone-treated D3.5 RhoAd/d CL, with parallel changes of HSP60
expression. These data demonstrated the in vivo function of RhoA in CL luteal
cell cytoskeleton integrity, cholesterol transport, StAR expression, and
progesterone synthesis, and a positive feedback on StAR expression in CL by
progesterone signaling. These findings provide insights into mechanisms of
progesterone insufficiency.
PMID- 28498973
TI - Chordoma Occurs in Young Children With Tuberous Sclerosis.
AB - Chordomas are rare bony neoplasms usually unassociated with a familial tumor
predisposition syndrome. The peak incidence of this midline axial skeletal tumor
is in adulthood but when very young children are affected, consideration should
be given to occurrence within the tuberous sclerosis (TS) complex, especially
when presenting in neonates <3 months of age. To call attention to this
association, we present a brachyury-immunopositive chordoma occurring in the
skull base of a 2-month-old male infant who was later realized to have metastases
to the subcutaneous tissues and lungs, as well as rhabdomyoma of the heart and
renal cysts/angiomyolipomas, that is, characteristic features of the TS complex.
We review the limited literature on this topic.
PMID- 28498974
TI - Strong transcription blockage mediated by R-loop formation within a G-rich
homopurine-homopyrimidine sequence localized in the vicinity of the promoter.
AB - Guanine-rich (G-rich) homopurine-homopyrimidine nucleotide sequences can block
transcription with an efficiency that depends upon their orientation, composition
and length, as well as the presence of negative supercoiling or breaks in the non
template DNA strand. We report that a G-rich sequence in the non-template strand
reduces the yield of T7 RNA polymerase transcription by more than an order of
magnitude when positioned close (9 bp) to the promoter, in comparison to that for
a distal (~250 bp) location of the same sequence. This transcription blockage is
much less pronounced for a C-rich sequence, and is not significant for an A-rich
sequence. Remarkably, the blockage is not pronounced if transcription is
performed in the presence of RNase H, which specifically digests the RNA strands
within RNA-DNA hybrids. The blockage also becomes less pronounced upon reduced
RNA polymerase concentration. Based upon these observations and those from
control experiments, we conclude that the blockage is primarily due to the
formation of stable RNA-DNA hybrids (R-loops), which inhibit successive rounds of
transcription. Our results could be relevant to transcription dynamics in vivo
(e.g. transcription 'bursting') and may also have practical implications for the
design of expression vectors.
PMID- 28498976
TI - Low back pain among taxi drivers: a cross-sectional study.
AB - Background: Low back pain (LBP) is a common occupational problem for drivers all
over the world. However, few epidemiological studies have investigated LBP among
taxi drivers. Aims: To investigate the prevalence of LBP and associated work
related factors among Chinese taxi drivers. Methods: A cross-sectional survey was
administered to all participants. Using cluster sampling, questionnaires were
collected from taxi drivers of three major taxi companies in Jinan, China.
Univariate and multivariate logistic regressions were used to estimate the odd
ratios (ORs) and 95% confidence intervals (CIs) among participants. Results: A
total of 800 taxi drivers were invited to take part, with a participation rate of
90%. The 1-year period prevalence of LBP was 54%. Multivariate logistic
regression analysis revealed that longer daily driving duration (OR 3.3, 95% CI
1.9-5.9), night shifts (OR 1.9, 95% CI 1.2-3.1) and increasing work years as a
taxi driver (OR 1.7, 95% CI 1.2-2.5) were associated with increased risk of
reporting LBP; while increased rest days per month (OR 0.8, 95% CI 0.7-0.9),
longer sleep duration (OR 0.7, 95% CI 0.5-0.9) and more physical activity (OR
0.5, 95% CI 0.3-0.8) were significantly associated with decreased risk of
reporting LBP. Conclusions: The prevalence of LBP among professional taxi drivers
in China was associated with a number of occupational features.
PMID- 28498978
TI - Patient reported outcome of adult perioperative anaesthesia in the United
Kingdom: a cross-sectional observational study.
PMID- 28498975
TI - Sustained efficacy, safety and patient-reported outcomes of certolizumab pegol in
axial spondyloarthritis: 4-year outcomes from RAPID-axSpA.
AB - Objective: The aim was to assess the long-term safety and efficacy of
certolizumab pegol over 4 years of continuous treatment in patients with axial
spondyloarthritis (axSpA), including both AS and non-radiographic (nr-) axSpA.
Methods: RAPID-axSpA was a phase 3 randomized trial, double blind and placebo
controlled to week 24, dose blind to week 48 and open label to week 204. Patients
had a clinical diagnosis of axSpA, meeting Assessment of SpondyloArthritis
international Society (ASAS) criteria, and had active disease. The assessed
outcomes included ASAS20, ASAS40, AS DAS (ASDAS), BASDAI, BASFI and BASMI scores,
along with selected measures of remission. Further patient-reported outcomes,
peripheral arthritis, enthesitis, uveitis and quality-of-life measures are also
reported. Results: Two hundred and eighteen of 325 patients randomized (AS: 121;
nr-axSpA: 97) received certolizumab pegol from week 0. Of these, 65% remained in
the study at week 204 (AS: 67%; nr-axSpA: 63%). Across all outcomes, for AS and
nr-axSpA, sustained improvements were observed to week 204 [week 204 overall
axSpA: ASAS20: 54.1% (non-responder imputation); 83.7% (observed case, OC);
ASAS40: 44.0% (non-responder imputation); 68.1% (OC); ASDAS inactive disease:
32.1% (last observation carried forward); 31.4% (OC)]. In the safety set (n =
315), there were 292.8 adverse events and 10.4 serious adverse events per 100
patient-years. No deaths were reported. Conclusion: In the first study to
evaluate the efficacy of an anti-TNF across both axSpA subpopulations,
improvements in clinical and patient-reported outcomes at 24 and 96 weeks were
sustained through 4 years of treatment, with no new safety signals. Trial
registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01087762.
PMID- 28498979
TI - Cohort Profile: The Tracking Opportunities and Problems Study (TOPP)-study of
Norwegian children and their parents followed from infancy to early adulthood.
PMID- 28498977
TI - Consequences of MEGF10 deficiency on myoblast function and Notch1 interactions.
AB - Mutations in MEGF10 cause early onset myopathy, areflexia, respiratory distress,
and dysphagia (EMARDD), a rare congenital muscle disease, but the pathogenic
mechanisms remain largely unknown. We demonstrate that short hairpin RNA (shRNA)
mediated knockdown of Megf10, as well as overexpression of the pathogenic human
p.C774R mutation, leads to impaired proliferation and migration of C2C12 cells.
Myoblasts from Megf10-/- mice and Megf10-/-/mdx double knockout (dko) mice also
show impaired proliferation and migration compared to myoblasts from wild type
and mdx mice, whereas the dko mice show histological abnormalities that are not
observed in either single mutant mouse. Cell proliferation and migration are
known to be regulated by the Notch receptor, which plays an essential role in
myogenesis. Reciprocal co-immunoprecipitation studies show that Megf10 and Notch1
interact via their respective intracellular domains. These interactions are
impaired by the pathogenic p.C774R mutation. Megf10 regulation of myoblast
function appears to be mediated at least in part via interactions with key
components of the Notch signaling pathway, and defects in these interactions may
contribute to the pathogenesis of EMARDD.
PMID- 28498980
TI - Fowl adenovirus serotype 4: Epidemiology, pathogenesis, diagnostic detection, and
vaccine strategies.
AB - Fowl adenovirus (FAdV) serotype-4 is highly pathogenic for chickens, especially
for broilers aged 3 to 5 wk, and it has emerged as one of the foremost causes of
economic losses to the poultry industry in the last 30 years. The liver is a
major target organ of FAdV-4 infections, and virus-infected chickens usually show
symptoms of hydropericardium syndrome. The virus is very contagious, and it is
spread both vertically and horizontally. It can be isolated from infected liver
homogenates and detected by several laboratory diagnostic methods (including an
agar gel immunodiffusion test, indirect immunofluorescence assays,
counterimmunoelectrophoresis, enzyme-linked immunosorbent assays, restriction
endonuclease analyses, polymerase chain reaction (PCR), real-time PCR, and high
resolution melting-curve analyses). Although inactivated vaccines have been
deployed widely to control the disease, attenuated live vaccines and subunit
vaccines also have been developed, and they are more attractive vaccine
candidates. This article provides a comprehensive review of FAdV-4, including its
epidemiology, pathogenesis, diagnostic detection, and vaccine strategies.
PMID- 28498982
TI - Using self-assessment to develop metacognition and self-regulated learners.
AB - Student success is too often challenged by a lack of metacognition and ability to
self-regulate learning. This commentary argues that the use of self-assessment to
increase student metacognition positively impacts student learning and self
regulation. In addition, several strategies for incorporating self-assessment
will be presented.
PMID- 28498981
TI - Splicing in immune cells-mechanistic insights and emerging topics.
AB - Differential splicing of mRNAs not only enables regulation of gene expression
levels, but also ensures a high degree of gene-product diversity. The extent to
which splicing of mRNAs is utilized as a mechanism in immune cells has become
evident within the last few years. Still, only a few of these mechanisms have
been well studied. In this review, we discuss some of the best-understood
mechanisms, for instance the differential splicing of CD45 in T cells, as well as
immunoglobulin genes in B cells. Beyond that we provide general mechanistic
insights on how, when and where this process takes place and discuss the current
knowledge regarding these topics in immune cells. We also highlight some of the
reported links to immune-related diseases, genome-wide sequencing studies that
revealed thousands of differentially spliced transcripts, as well as splicing
studies on immune cells that remain mechanistically not fully understood. We
thereby display potential emerging topics for future studies centered on splicing
mechanisms in immune cells.
PMID- 28498983
TI - Atypical hand, foot and mouth disease due to Coxsackievirus A6 in a traveler
returning from Indonesia to Italy.
PMID- 28498984
TI - Inheritance of vernalization memory at FLOWERING LOCUS C during plant
regeneration.
AB - Specific gene states can be transmitted to subsequent cell generations through
mitosis involving particular chromatin (epigenetic) states. During reproduction
of plants and animals, however, most epigenetic states are reset to allow
development to start anew. Flowering is one of the critical developmental steps
by which plants acquire their reproductive capacity. This phase transition is
controlled by environmental signals and autonomous regulation. The FLOWERING
LOCUS C (FLC) gene is a flowering repressor that is epigenetically silenced after
long-term exposure to cold, ensuring flowering in the spring season. In
Arabidopsis thaliana, epigenetically silenced FLC expression is reset during
sexual reproduction. Plants have a remarkable potential to regenerate from
somatic cells. However, little is known about whether the regeneration process is
similar to sexual reproduction in terms of affecting chromatin states. Here, we
tested whether FLC silencing is reset during in vitro regeneration.
Transcriptional repression and high H3K27me3 at FLC were both stably transmitted,
resulting in early flowering in regenerated shoots. Thus, the silenced epigenetic
state of FLC is reset only during sexual reproduction and not during in vitro
regeneration. In contrast, the active epigenetic state of FLC was only partially
maintained through in vitro reproduction, suggesting that regeneration causes
stochastic FLC silencing.
PMID- 28498985
TI - HIV Antibody Level as a Marker of HIV Persistence and Low-Level Viral
Replication.
AB - Background: Human immunodeficiency virus (HIV) antibodies are generated and
maintained by ongoing systemic expression of HIV antigen. We investigated whether
HIV antibody responses as measured by high-throughput quantitative and
qualitative assays could be used to indirectly measure persistent HIV replication
in individuals receiving antiretroviral therapy (ART). Methods: HIV antibody
responses were measured over time in the presence or absence of suppressive ART
and were compared to the HIV reservoir size and expression of antiviral
restriction factors. Results: Among untreated individuals, including both elite
controllers (ie, persons with a viral load of <=40 copies/mL) and noncontrollers,
antibody parameters were stable over time and correlated with the individual
viral load. Viral suppression with ART led to a progressive decline in antibody
responses after treatment induction that persisted for 5-7 years. Higher levels
of HIV antibodies during suppressive therapy were associated with later
initiation of ART after infection, with higher DNA and cell-associated RNA
levels, and with lower expression of multiple anti-HIV host restriction factors.
Discussion: These findings suggest that declining antibody levels during ART
reflect lower levels of antigen production and/or viral replication in the
persistent HIV reservoir. Results of relatively inexpensive and quantitative HIV
antibody assays may be useful indirect markers that enable efficient monitoring
of the viral reservoir and suppression during functional-cure interventions.
PMID- 28498986
TI - Sequence of inoculation influences the nature of extracellular polymeric
substances and biofilm formation in Azotobacter chroococcum and Trichoderma
viride.
AB - Extracellular polymeric substances (EPS) are important structural components of
biofilms. In the present study, the EPS in biofilms developed using two
agriculturally beneficial organisms-Azotobacter chroococcum (Az) and Trichoderma
viride (Tv) were quantified and characterised. Time course experiments were
undertaken to optimise the EPS yield of biofilm samples resulting from coculture
and staggered inoculation. The EPS produced during biofilm formation was found to
differ quantitatively and qualitatively in individual cultures (Az alone, Tv
alone), and in treatments differing in the sequence of inoculation of bacterium
and fungus (Az + Tv coculture, staggered inoculation of Az followed by Tv i.e. Az
- Tv, or Tv followed by Az i.e. Tv - Az). Significant enhancement in terms of
growth and biofilm formation, as compared to individual inoculation was recorded,
with Tv - Az exhibiting higher values of these attributes. The EPS from biofilms
showed significantly higher concentrations of protein, acetyl, and uronic acids,
while planktonic EPS recorded higher total carbohydrates. Fourier transform
infrared spectroscopy analyses illustrated the significant influence on chemical
and structural aspects of EPS (planktonic and biofilm). This represents a first
report correlating EPS production, cell aggregation and biofilm formation during
bacterial-fungal biofilm development, which can have implications in the
colonisation of soil and plants.
PMID- 28498987
TI - Genetic Structure and Phylogeography of the Leopard Cat (Prionailurus
bengalensis) Inferred from Mitochondrial Genomes.
AB - The Leopard cat Prionailurus bengalensis is a habitat generalist that is widely
distributed across Southeast Asia. Based on morphological traits, this species
has been subdivided into 12 subspecies. Thus far, there have been few molecular
studies investigating intraspecific variation, and those had been limited in
geographic scope. For this reason, we aimed to study the genetic structure and
evolutionary history of this species across its very large distribution range in
Asia. We employed both PCR-based (short mtDNA fragments, 94 samples) and high
throughput sequencing based methods (whole mitochondrial genomes, 52 samples) on
archival, noninvasively collected and fresh samples to investigate the
distribution of intraspecific genetic variation. Our comprehensive sampling
coupled with the improved resolution of a mitochondrial genome analyses provided
strong support for a deep split between Mainland and Sundaic Leopard cats.
Although we identified multiple haplogroups within the species' distribution, we
found no matrilineal evidence for the distinction of 12 subspecies. In the
context of Leopard cat biogeography, we cautiously recommend a revision of the
Prionailurus bengalensis subspecific taxonomy: namely, a reduction to 4
subspecies (2 mainland and 2 Sundaic forms).
PMID- 28498988
TI - Complementary Roles of Phenotype and Genotype in Subspecies Delimitation.
PMID- 28498989
TI - Determination of the Genetic Architecture Underlying Short Wavelength Sensitivity
in Lake Malawi Cichlids.
AB - African cichlids are an exemplary system to study organismal diversity and rapid
speciation. Species differ in external morphology including jaw shape and body
coloration, but also differ in sensory systems including vision. All cichlids
have 7 cone opsin genes with species differing broadly in which opsins are
expressed. The differential opsin expression results in closely related species
with substantial differences in spectral sensitivity of their photoreceptors. In
this work, we take a first step in determining the genetic basis of opsin
expression in cichlids. Using a second generation cross between 2 species with
different opsin expression patterns, we make a conservative estimate that short
wavelength opsin expression is regulated by a few loci. Genetic mapping in 96 F2
hybrids provides clear evidence of a cis-regulatory region for SWS1 opsin that
explains 34% of the variation in expression between the 2 species. Additionally,
in situ hybridization has shown that SWS1 and SWS2B opsins are coexpressed in
individual single cones in the retinas of F2 progeny. Results from this work will
contribute to a better understanding of the genetic architecture underlying opsin
expression. This knowledge will help answer long-standing questions about the
evolutionary processes fundamental to opsin expression variation and how this
contributes to adaptive cichlid divergence.
PMID- 28498990
TI - Genetic Kinship Analyses Reveal That Gray's Beaked Whales Strand in Unrelated
Groups.
AB - Some marine mammals are so rarely seen that their life history and social
structure remain a mystery. Around New Zealand, Gray's beaked whales (Mesoplodon
grayi) are almost never seen alive, yet they are a commonly stranded species.
Gray's are unique among the beaked whales in that they frequently strand in
groups, providing an opportunity to investigate their social organization. We
examined group composition and genetic kinship in 113 Gray's beaked whales with
samples collected over a 20-year period. Fifty-six individuals stranded in 19
groups (2 or more individuals), and 57 whales stranded individually.
Mitochondrial control region haplotypes and microsatellite genotypes (16 loci)
were obtained for 103 whales. We estimated pairwise relatedness between all pairs
of individuals and average relatedness within, and between, groups. We identified
6 mother-calf pairs and 2 half-siblings, including 2 whales in different
strandings 17 years and 1500 km apart. Surprisingly, none of the adults stranding
together were related suggesting that groups are not formed through the retention
of kin. These data suggest that both sexes may disperse from their mothers, and
groups consisting of unrelated subadults are common. We also found no instances
of paternity within the groups. Our results provide the first insights into
dispersal, social organization, and the mating system in this rarely sighted
species. Why whales strand is still unknown but, in Gray's beaked whales, the
dead can tell us much about the living.
PMID- 28498991
TI - Population Differentiation in Common Walnut (Juglans regia L.) across Major Parts
of Its Native Range-Insights from Molecular and Morphometric Data.
AB - Juglans regia is an economically highly important species for fruit and wood
production in the warm temperate and subtropical zones of the Northern
Hemisphere. Besides the natural influence of climatic and geomorphological
barriers, its genetic structure has been strongly modified by humans and the
population history is still unclear. For this reason, we investigated mainly
natural walnut populations across the Eurasian continent on a molecular (44
populations, 581 trees) and morphometric level (23 populations, 1391 ripe nuts).
Population genetic diversity and differentiation were examined by using 7
microsatellite loci. Morphometric characteristics of the nuts (mainly roundness
index and nut density) were used to estimate trait variation and population
differentiation. Highest allelic richness Rs12 = 7.05 was observed in a Pakistani
and the lowest value Rs12 = 3.04 in a Kyrgyz population. The genetic
differentiation among populations was high (FST = 0.217; RST = 0.530) indicating
a strong phylogeographic pattern. While variation of the roundness index within
single populations was high, this trait neither differentiated geographical
regions nor was it associated to genetic clusters. Approximated QST based on this
trait equalled FST, while approximated QST based on nut density considerably
exceeded FST, indicating selection. Nut density was moderately correlated with
altitude, latitude, and longitude, and differentiated populations according to
their origin. Pakistani and Indian populations showed highest nut densities.
These South Asian populations contain putatively ancestral nut forms, which
probably have been lost in other populations as a consequence of human selection.
PMID- 28498992
TI - Reproductive Strategy of the Polyploid Species Varronia curassavica Jacq. in
Restinga Environment.
AB - This study aimed to elucidate the breeding strategies of Varronia curassavica, an
important medicinal species associated with Brazilian restinga. This was
accomplished by combining phenological and genetic data. Every 2 weeks over a
period of 2 years, we measured flowering and fruiting phenology to evaluate the
activity and intensity of phenophases (n = 60). We evaluated the mating system,
pollen ovule ratio and genotypes from progeny and mother plants using 8 nuclear
microsatellite loci. We observed flowering and fruiting of V. curassavica at low
intensity throughout the entire year, but with 2 distinct peaks, one of which was
seasonal, corresponding to the period of gradual increase of temperature and
photoperiod. Overlapping of flowering and fruiting strategies favors gene flow
among different groups of individuals and between populations by attraction of
fauna throughout the year. Analysis of the mating system indicates that V.
curassavica is a typical outcrossed species (t^ = 0.98; pollen/ovule ratio =
7087.50). Combining phenology with genetic studies improved our understanding of
the reproductive strategies of this species. The typical outcrossing system of V.
curassavica reflects the existence of functional self-incompatibility mechanisms
still unaffected by changes in genetic balance by polyploidy.
PMID- 28498993
TI - DEOGEN2: prediction and interactive visualization of single amino acid variant
deleteriousness in human proteins.
AB - High-throughput sequencing methods are generating enormous amounts of genomic
data, giving unprecedented insights into human genetic variation and its relation
to disease. An individual human genome contains millions of Single Nucleotide
Variants: to discriminate the deleterious from the benign ones, a variety of
methods have been developed that predict whether a protein-coding variant likely
affects the carrier individual's health. We present such a method, DEOGEN2, which
incorporates heterogeneous information about the molecular effects of the
variants, the domains involved, the relevance of the gene and the interactions in
which it participates. This extensive contextual information is non-linearly
mapped into one single deleteriousness score for each variant. Since for the non
expert user it is sometimes still difficult to assess what this score means, how
it relates to the encoded protein, and where it originates from, we developed an
interactive online framework (http://deogen2.mutaframe.com/) to better present
the DEOGEN2 deleteriousness predictions of all possible variants in all human
proteins. The prediction is visualized so both expert and non-expert users can
gain insights into the meaning, protein context and origins of each prediction.
PMID- 28498994
TI - ThreaDomEx: a unified platform for predicting continuous and discontinuous
protein domains by multiple-threading and segment assembly.
AB - We develop a hierarchical pipeline, ThreaDomEx, for both continuous domain (CD)
and discontinuous domain (DCD) structure predictions. Starting from a query
sequence, ThreaDomEx first threads it through the PDB to identify multiple
structure templates, where a profile of domain conservation score (DC-score) is
derived for domain-segment assignment. To further detect DCDs that consist of
separated segments along the sequence, a boundary-clustering algorithm is used to
refine the DCD-linker locations. In case that the templates do not contain DCDs,
a domain-segment assembly process, guided by symmetry comparison, is applied for
further DCD detections. ThreaDomEx was tested a set of 1111 proteins and achieved
a normalized domain overlap score of 89.3% compared to experimental data, which
is significantly higher than other state-of-the-art methods. It also recalls
26.7% of DCDs with 72.7% precision on the proteins for which threading failed to
detect any DCDs. The server provides facilities for users to interactively refine
the domain models by adjusting DC-score threshold, deleting and adding domain
linkers, and assembling domain segments, which are particularly helpful for the
hard targets for which current methods have a low accuracy while human-expert
knowledge and experimental insights can be used for refining models. ThreaDomEX
server is available at http://zhanglab.ccmb.med.umich.edu/ThreaDomEx.
PMID- 28498995
TI - Features of Ebola Virus Disease at the Late Outbreak Stage in Sierra Leone:
Clinical, Virological, Immunological, and Evolutionary Analyses.
AB - We performed Ebola virus disease diagnosis and viral load estimation for Ebola
cases in Sierra Leone during the late stage of the 2014-2015 outbreak (January
March 2015) and analyzed antibody and cytokine levels and the viral genome
sequences. Ebola virus disease was confirmed in 86 of 1001 (9.7%) patients, with
an overall case fatality rate of 46.8%. Fatal cases exhibited significantly
higher levels of viral loads, cytokines, and chemokines at late stages of
infection versus early stage compared with survivors. The viruses converged in a
new clade within sublineage 3.2.4, which had a significantly lower case fatality
rate.
PMID- 28498996
TI - Protective Factors in the Intestinal Microbiome Against Clostridium difficile
Infection in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation.
AB - Background: Clostridium difficile infection (CDI) is a frequent complication in
recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT), who
receive intensive treatments that significantly disrupt the intestinal
microbiota. In this study, we examined the microbiota composition of allo-HSCT
recipients to identify bacterial colonizers that confer protection against CDI
after engraftment. Methods: Feces collected from adult recipients allo-HSCT at
engraftment were analyzed; 16S ribosomal RNA genes were sequenced and analyzed
from each sample. Bacterial taxa with protective effects against development of
CDI were identified by means of linear discriminant analysis effect size analysis
and then further assessed with clinical predictors of CDI using survival
analysis. Results: A total of 234 allo-HSCT recipients were studied;
postengraftment CDI developed in 53 (22.6%). Within the composition of the
microbiota, the presence of 3 distinct bacterial taxa was correlated with
protection against CDI: Bacteroidetes, Lachnospiraceae, and Ruminococcaceae.
Colonization with these groups at engraftment was associated with a 60% lower
risk of CDI, independent of clinical factors. Conclusions: Colonization with
these 3 bacterial groups is associated with a lower risk of CDI. These groups
have been shown to be vital components of the intestinal microbiota. Targeted
efforts to maintain them may help minimize the risk of CDI in this at-risk
population.
PMID- 28498997
TI - Initiation of gametocytogenesis at very low parasite density in Plasmodium
falciparum infection.
AB - The recent focus on the elimination of malaria has led to an increased interest
in the role of sexual stages in its transmission. We introduce Plasmodium
falciparum gametocyte exported protein-5 (PfGEXP5) transcript analysis as an
important tool for evaluating the earliest (ring) stage sexual gametocytes in the
blood of infected individuals. We show that gametocyte rings are detected in the
peripheral blood immediately following establishment of asexual infections
without the need for triggers such as high-density asexual parasitemia or drug
treatment. Committed gametocytes are refractory to the commonly used drug
piperaquine, and mature gametocytes reappear in the bloodstream 10 days after the
initial appearance of gametocyte rings. A further wave of commitment is observed
following recrudescent asexual parasitemia, and these gametocytes are again
refractory to piperaquine treatment. This work has implications for monitoring
gametocyte and transmission dynamics and responses to drug treatment.
PMID- 28498998
TI - Mechanism of Human Influenza Virus RNA Persistence and Virion Survival in Feces:
Mucus Protects Virions From Acid and Digestive Juices.
AB - Although viral RNA or infectious virions have been detected in the feces of
individuals infected with human influenza A and B viruses (IAV/IBV), the
mechanism of viral survival in the gastrointestinal tract remains unclear. We
developed a model that attempts to recapitulate the conditions encountered by a
swallowed virus. While IAV/IBV are vulnerable to simulated digestive juices
(gastric acid and bile/pancreatic juice), highly viscous mucus protects viral RNA
and virions, allowing the virus to retain its infectivity. Our results suggest
that virions and RNA present in swallowed mucus are not inactivated or degraded
by the gastrointestinal environment, allowing their detection in feces.
PMID- 28498999
TI - The Effect of Religion and Spirituality on Cognitive Function: A Systematic
Review.
AB - Purpose of the Study: The maintenance of cognitive health is an important
component of healthy aging. Abnormal cognitive decline can signal the onset of
dementing disorders such as Alzheimer's disease (AD). Normal cognitive decline
can also adversely affect the health of aging populations. We investigated the
association between religious/spiritual involvement (R/SI) and cognitive function
in adults of any age and any setting. We also examined whether social engagement
acts as a mediator or moderator of the effect of R/SI on cognitive function, and
whether the association between R/SI and cognitive function differs according to
how each of these constructs is measured. Design and Methods: We conducted a
systematic review of articles published between 1990 and September 2016 by
searching OVID MEDLINE, PSYCHINFO, EMBASE, and Google Advanced Search. We
included studies with a comparison group (cohort, case-control, cross-sectional)
that reported on R/SI (exposure) and cognitive function (outcome). Results: Of
the 6,300 citations obtained in the literature search, 17 met our eligibility
criteria and were included in the review. Most of the included studies (82%)
reported positive associations between R/SI and cognitive function. R/SI appears
to be protective against cognitive decline in middle- and old-age adults.
Implications: Public health practitioners should not overlook the benefits of
enabling religious/spiritual practices among religious adults (i.e., offering
ride programs could help isolated elders attend religious gatherings).
PMID- 28499000
TI - 238U CONTENT IN URINE OF URANIUM MINERS AND ITS MODELED VALUES.
AB - The aim of the study is to make a comparison of daily 238U excretion in urine
among 115 active uranium miners and its modeled values obtained from inhalation
intake of long-lived alpha emitters as measured by personal dosemeters and
assessed by biokinetic models for different absorption parameters settings for
inhaled uranium. A total of 144 spot samples of urine were collected. The 238U
content was measured using high-resolution inductively coupled plasma mass
spectrometry method. To obtain estimates of the daily excreted values, the daily
values were calculated according to the expected daily excretion of creatinine
assessed individually for each miner. When determining the relation between the
experimentally found data and the modeled data, a high emphasis was placed on
uncertainty of the both compared quantities. All the tested absorption parameters
settings produced in average 1.4-4.7-fold higher values than the experimentally
found values in the urine.
PMID- 28499002
TI - Moving Rehabilitation Research Forward at NIH.
PMID- 28499001
TI - Is Pelvic-Floor Muscle Training a Physical Therapy or a Behavioral Therapy? A
Call to Name and Report the Physical, Cognitive, and Behavioral Elements.
AB - This perspective article explores whether pelvic-floor muscle training (PFMT) for
the management of female urinary incontinence and prolapse is a physical therapy
or a behavioral therapy. The primary aim is to demonstrate that it is both. A
secondary aim is to show that the plethora of terms used for PFMT is potentially
confusing and that current terminology inadequately represents the full intent,
content, and delivery of this complex intervention. While physical therapists may
be familiar with exercise terms, the details are often incompletely reported;
furthermore, physical therapists are less familiar with the terminology used in
accurately representing cognitive and behavioral therapy interventions, which
results in these elements being even less well reported. Thus, an additional aim
is to provide greater clarity in the terminology used in the reporting of PFMT
interventions, specifically, descriptions of the exercise and behavioral
elements. First, PFMT is described as a physical therapy and as an exercise
therapy informed predominantly by the discipline of physical therapy. However,
effective implementation requires use of the cognitive and behavioral
perspectives of the discipline of psychology. Second, the theoretical
underpinning of the psychology-informed elements of PFMT is summarized. Third, to
address some identified limitations and confusion in current terminology and
reporting, recommendations for ways in which physical therapists can incorporate
the psychology-informed elements of PFMT alongside the more familiar exercise
therapy-informed elements are made. Fourth, an example of how both elements can
be described and reported in a PFMT intervention is provided. In summary, this
perspective explores the underlying concepts of PFMT to demonstrate that it is
both a physical intervention and a behavioral intervention and that it can and
should be described as such, and an example of the integration of these elements
into clinical practice is provided.
PMID- 28499004
TI - Rehabilitation Research at the National Institutes of Health:: Moving the Field
Forward (Executive Summary).
AB - Approximately 53 million Americans live with a disability. For decades, the
National Institutes of Health (NIH) has been conducting and supporting research
to discover new ways to minimize disability and enhance the quality of life of
people with disabilities. After the passage of the American With Disabilities
Act, the NIH established the National Center for Medical Rehabilitation Research
with the goal of developing and implementing a rehabilitation research agenda.
Currently, a total of 17 institutes and centers at NIH invest more than $500
million per year in rehabilitation research. Recently, the director of NIH, Dr
Francis Collins, appointed a Blue Ribbon Panel to evaluate the status of
rehabilitation research across institutes and centers. As a follow-up to the work
of that panel, NIH recently organized a conference under the title
"Rehabilitation Research at NIH: Moving the Field Forward." This report is a
summary of the discussions and proposals that will help guide rehabilitation
research at NIH in the near future.This article is being published almost
simultaneously in the following six journals: American Journal of Occupational
Therapy, American Journal of Physical Medicine and Rehabilitation, Archives of
Physical Medicine and Rehabilitation, Neurorehabilitation and Neural Repair,
Physical Therapy, and Rehabilitation Psychology. Citation information is as
follows: Frontera WR, Bean JF, Damiano D, et al. Am J Phys Med Rehabil.
2017;97(4):393-403.
PMID- 28499003
TI - National Institutes of Health Research Plan on Rehabilitation: NIH Medical
Rehabilitation Coordinating Committee.
AB - One in five Americans experiences disability that affects their daily function
because of impairments in mobility, cognitive function, sensory impairment, or
communication impairment. The need for rehabilitation strategies to optimize
function and reduce disability is a clear priority for research to address this
public health challenge. The National Institutes of Health (NIH) recently
published a Research Plan on Rehabilitation that provides a set of priorities to
guide the field over the next 5 years. The plan was developed with input from
multiple Institutes and Centers within the NIH, the National Advisory Board for
Medical Rehabilitation Research, and the public. This article provides an
overview of the need for this research plan, an outline of its development, and a
listing of six priority areas for research. The NIH is committed to working with
all stakeholder communities engaged in rehabilitation research to track progress
made on these priorities and to work to advance the science of medical
rehabilitation.This article is being published almost simultaneously in the
following six journals: American Journal of Occupational Therapy, American
Journal of Physical Medicine and Rehabilitation, Archives of Physical Medicine
and Rehabilitation, Neurorehabilitation and Neural Repair, Physical Therapy, and
Rehabilitation Psychology. Citation information is as follows: NIH Medical
Rehabilitation Coordinating Committee. Am J Phys Med Rehabil. 2017;97(4):404-407.
PMID- 28499005
TI - Rehabilitation for Women and Men With Pelvic-Floor Dysfunction.
PMID- 28499006
TI - Clinical characteristics and change in the antibody titres of patients with anti
MDA5 antibody-positive inflammatory myositis.
AB - Objective: The aim of this study was to evaluate the clinical characteristics of
patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody
positive inflammatory myositis, and the change in anti-MDA5 antibody titres
before and after onset. Method: For 105 PM/DM patients, newly diagnosed in our
hospital within the period 2008-2016, serum anti-MDA5 antibody levels were
measured at diagnosis and after treatment by ELISA using the MESACUP anti-MDA5
test. The relationships between anti-MDA5 antibody levels and clinical
manifestations, laboratory data, and mortality were examined. Result: Compared
with patients who were anti-MDA5 antibody negative, those who were antibody
positive demonstrated more frequent dermatitis, clinically amyopathic DM,
interstitial lung disease and rapid-progressive interstitial lung disease, as
well as significantly higher serum ferritin, significantly lower creatine kinase
and aldolase, and significantly less frequent ANA (?1:160) and anti-cytoplasmic
pattern of ANA staining positivity. Anti-MDA5 antibody titres were examined
before disease onset in two patients; one showed antibody positivity with low
titres 2 years earlier, while both exhibited increased titres at onset. Anti-MDA5
antibody titres declined significantly less in survivors than in non-survivors
after treatment; however, there was no significant difference between the two
groups when the rate was compared at 2 months after treatment. Conclusion: An
initial decrease in anti-MDA5 antibody titre after commencement of treatment was
observed in most of the patients, including in fatal cases, suggesting that this
may not necessarily be a useful marker for treatment of patients with DM.
PMID- 28499007
TI - Shifts in microbial trophic strategy explain different temperature sensitivity of
CO2 flux under constant and diurnally varying temperature regimes.
AB - Understanding soil CO2 flux temperature sensitivity (Q10) is critical for
predicting ecosystem-level responses to climate change. Yet, the effects of
warming on microbial CO2 respiration still remain poorly understood under current
Earth system models, partly as a result of thermal acclimation of organic matter
decomposition. We conducted a 117-day incubation experiment under constant and
diurnally varying temperature treatments based on four forest soils varying in
vegetation stand and soil horizon. Our results showed that Q10 was greater under
varying than constant temperature regimes. This distinction was most likely
attributed to differences in the depletion of available carbon between constant
high and varying high-temperature treatments, resulting in significantly higher
rates of heterotrophic respiration in the varying high-temperature regime. Based
on 16S rRNA gene sequencing data using Illumina, the varying high-temperature
regime harbored higher prokaryotic alpha-diversity, was more dominated by the
copiotrophic strategists and sustained a distinct community composition, in
comparison to the constant-high treatment. We found a tightly coupled
relationship between Q10 and microbial trophic guilds: the copiotrophic
prokaryotes responded positively with high Q10 values, while the oligotrophs
showed a negative response. Effects of vegetation stand and soil horizon
consistently supported that the copiotrophic vs oligotrophic strategists
determine the thermal sensitivity of CO2 flux. Our observations suggest that
incorporating prokaryotic functional traits, such as shifts between copiotrophy
and oligotrophy, is fundamental to our understanding of thermal acclimation of
microbially mediated soil organic carbon cycling. Inclusion of microbial
functional shifts may provide the potential to improve our projections of
responses in microbial community and CO2 efflux to a changing environment in
forest ecosystems.
PMID- 28499008
TI - RiPPMiner: a bioinformatics resource for deciphering chemical structures of RiPPs
based on prediction of cleavage and cross-links.
AB - Ribosomally synthesized and post-translationally modified peptides (RiPPs)
constitute a rapidly growing class of natural products with diverse structures
and bioactivities. We have developed RiPPMiner, a novel bioinformatics resource
for deciphering chemical structures of RiPPs by genome mining. RiPPMiner derives
its predictive power from machine learning based classifiers, trained using a
well curated database of more than 500 experimentally characterized RiPPs.
RiPPMiner uses Support Vector Machine to distinguish RiPP precursors from other
small proteins and classify the precursors into 12 sub-classes of RiPPs. For
classes like lanthipeptide, cyanobactin, lasso peptide and thiopeptide, RiPPMiner
can predict leader cleavage site and complex cross-links between post
translationally modified residues starting from genome sequences. RiPPMiner can
identify correct cross-link pattern in a core peptide from among a very large
number of combinatorial possibilities. Benchmarking of prediction accuracy of
RiPPMiner on a large lanthipeptide dataset indicated high sensitivity,
specificity, accuracy and precision. RiPPMiner also provides interfaces for
visualization of the chemical structure, downloading of simplified molecular
input line-entry system and searching for RiPPs having similar sequences or
chemical structures. The backend database of RiPPMiner provides information about
modification system, precursor sequence, leader and core sequence, modified
residues, cross-links and gene cluster for more than 500 experimentally
characterized RiPPs. RiPPMiner is available at
http://www.nii.ac.in/rippminer.html.
PMID- 28499010
TI - Acute eosinophilic pneumonia following artenimol-piperaquine exposure.
AB - Acute eosinophilic pneumonia (AEP) has been reported following chloroquine or
mefloquine exposure, both structurally related to piperaquine. We report a case
of AEP with typical CT scan patterns, hypereosinophilia in blood (9.8 109/l), and
bronchoalveolar lavage (78% of 600 000 cells/ml), 10 days after artenimol
piperaquine exposure in a 26-year-old man.
PMID- 28499009
TI - A viral suppressor of RNA silencing inhibits ARGONAUTE 1 function by precluding
target RNA binding to pre-assembled RISC.
AB - In most eukaryotes, RNA silencing is an adaptive immune system regulating key
biological processes including antiviral defense. To evade this response, viruses
of plants, worms and insects have evolved viral suppressors of RNA silencing
proteins (VSRs). Various VSRs, such as P1 from Sweet potato mild mottle virus
(SPMMV), inhibit the activity of RNA-induced silencing complexes (RISCs)
including an ARGONAUTE (AGO) protein loaded with a small RNA. However, the
specific mechanisms explaining this class of inhibition are unknown. Here, we
show that SPMMV P1 interacts with AGO1 and AGO2 from Arabidopsis thaliana, but
solely interferes with AGO1 function. Moreover, a mutational analysis of a newly
identified zinc finger domain in P1 revealed that this domain could represent an
effector domain as it is required for P1 suppressor activity but not for AGO1
binding. Finally, a comparative analysis of the target RNA binding capacity of
AGO1 in the presence of wild-type or suppressor-defective P1 forms revealed that
P1 blocks target RNA binding to AGO1. Our results describe the negative
regulation of RISC, the small RNA containing molecular machine.
PMID- 28499011
TI - Fatal case of chikungunya and concomitant thrombotic thrombocytopenic purpura in
French Guiana during air flight medical evacuation.
AB - Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy
associated to severe ADAMTS13 deficiency. It has been linked to various viral
infections. Among arboviruses, only Crimean-Congo haemorrhagic fever and dengue
fever have been linked to this severe disease. We report the first documented
case of TTP concomitant to Chikungunya virus infection.
PMID- 28499012
TI - Resistance to Alzheimer Disease Neuropathologic Changes and Apparent Cognitive
Resilience in the Nun and Honolulu-Asia Aging Studies.
AB - Two population-based studies key to advancing knowledge of brain aging are the
Honolulu-Asia Aging Study (HAAS) and the Nun Study. Harmonization of their
neuropathologic data allows cross comparison, with findings common to both
studies likely generalizable, while distinct observations may point to aging
brain changes that are dependent on sex, ethnicity, environment, or lifestyle
factors. Here, we expanded the neuropathologic evaluation of these 2 studies
using revised NIA-Alzheimer's Association guidelines and compared directly the
neuropathologic features of resistance and apparent cognitive resilience. There
were significant differences in prevalence of Alzheimer disease neuropathologic
change, small vessel vascular brain injury, and Lewy body disease between these 2
studies, suggesting that sex, ethnicity, and lifestyle factors may significantly
influence resistance to developing brain injury with age. In contrast,
hippocampal sclerosis prevalence was very similar, but skewed to poorer cognitive
performance, suggesting that hippocampal sclerosis could act sequentially with
other diseases to impair cognitive function. Strikingly, despite these observed
differences, the proportion of individuals resistant to all 4 diseases of brain
or displaying apparent cognitive resilience was virtually identical between HAAS
and Nun Study participants. Future in vivo validation of these results awaits
comprehensive biomarkers of these 4 brain diseases.
PMID- 28499014
TI - Captive Ancestry Upwardly Biases Estimates of Relative Reproductive Success.
AB - Supplementation programs, which release captive-born individuals into the wild,
are commonly used to demographically bolster declining populations. In order to
evaluate the effectiveness of these programs, the reproductive success of captive
born individuals released into the wild is often compared to the reproductive
success of wild-born individuals in the recipient population (relative
reproductive success, RRS). However, if there are heritable reductions in fitness
associated with captive breeding, gene flow from captive-born individuals into
the wild population can reduce the fitness of the wild population. Here, we show
that when captive ancestry in the wild population reduces mean population
fitness, estimates of RRS are upwardly biased, meaning that the relative fitness
of captive-born individuals is over-estimated. Furthermore, the magnitude of this
bias increases with the length of time that a supplementation program has been
releasing captive-born individuals. This phenomenon has long-term conservation
impacts since management decisions regarding the design of a supplementation
program and the number of individuals to release can be based, at least in part,
on RRS estimates. Therefore, we urge caution in the interpretation of relative
fitness measures when the captive ancestry of the wild population cannot be
precisely measured.
PMID- 28499013
TI - GANTRY ANGULATION EFFECTS ON CT DOSE ALONG THE Z-AXIS DIRECTION IN HEAD
EXAMINATIONS.
AB - The purpose of this study was to evaluate the effects of the gantry angulation on
dose profiles along the z-axis, the CTDIW value and the CTDIW efficiency in the
head examinations. A Monte Carlo simulation model of a GE LightSpeed 16-slice CT
scanner was developed by a GATE toolkit. The CTDI100 in air at the isocenter and
in a head dosimetry phantom were measured using a pencil ion chamber. Dose
profiles were studied in the central and peripheral holes of the head phantom
using thermoluminescence LiF disc dosemeters for gantry angulations of 0 degrees
, 10 degrees and 20 degrees . Results show a small shift for only the peripheral
dose profiles with increasing the gantry angulation (maximum shift of 24 mm at 20
degrees ). The peak amplitude of the dose profiles was reduced for both of the
central and peripheral holes by ~5%, while the CTDIW values and the CTDIW
efficiencies did not change significantly.
PMID- 28499015
TI - MRI 'EXPOSIMETRY': HOW TO ANALYZE, COMPARE AND REPRESENT WORKER EXPOSURE TO
STATIC MAGNETIC FIELD?
AB - Worker exposure to electromagnetic fields (EMF) is a growing concern of
international commissions. A European directive from 2013 (2013/35/EU) recommend
to estimate or measure EMF exposure of all exposed workers. Magnetic resonance
imaging (MRI) workers are specially concerned by this point because they work all
day long in the vicinity of a very strong magnet (generally 1.5 or 3 T), which
cannot be turned off. Setting up a magnetic field monitoring device on these
workers would therefore be a good way to ensure their security. European
directive threshold adequacy could then be verified. But this verification does
not ensure a complete analysis of the worker exposure. Such an analysis based on
quality control charts and exposure time's metrics has been described in this
paper. The proposed magnetic field exposure analysis has additionally been tested
on a long-term exposure follow-up of 18 MRI workers during 2 months.
PMID- 28499016
TI - Minimally Invasive Transforaminal Lumbar Interbody Fusion Using Banana-Shaped and
Straight Cages: Radiological and Clinical Results from a Prospective Randomized
Clinical Trial.
AB - BACKGROUND: In minimally invasive transforaminal lumbar interbody fusion (MIS
TLIF), cage type and position play important roles in fusion achievement and
sagittal alignment correction. However, no prospective randomized comparison of
the results using different types of cage has been reported to date. OBJECTIVE:
To compare the radiological and clinical outcomes of unilateral MIS-TLIF using 2
types of cage. METHODS: All candidates for single-level MIS-TLIF were randomized
into banana-shaped cage and straight-cage groups. Plain radiographs and computed
tomography scans were used for assessment of cage positions, fusion status, disc
height, segmental lordotic angle, cage subsidence, and pelvic parameters.
Clinical outcome was assessed using visual analog scale and Oswestry Disability
Index scores. RESULTS: Forty-four and 40 consecutive patients were operated on
using banana-shaped and straight cages, respectively. Cage position was more
anterior and lateral in the straight-cage group and more medial and posterior in
the banana-shaped cage group. Solid fusion was achieved in 95.2% and 96.6% of the
2 groups, respectively, at 12 mo. The change in disc height and segmental
lordotic angle postoperatively was significantly greater in the banana-shaped
cage group. The incidence of subsidence during follow-up was significantly higher
in the banana-shaped cage group (P < .04). Clinically, the visual analog scale
and Oswestry Disability Index scores decreased significantly after surgery in
both groups, with no significant difference between the groups. CONCLUSION: Our
preliminary outcomes suggest that the subsidence rate may be higher using banana
shaped cages in MIS-TLIF, possibly due to their more medial final position.
PMID- 28499017
TI - Introduction to the Special Section: Disorders of Sex Development.
PMID- 28499020
TI - Letter: Rerupture of a Blister Aneurysm After Treatment With a Single Flow
Diverting Stent.
PMID- 28499019
TI - T-cadherin gene variants are associated with nephropathy in subjects with type 1
diabetes.
AB - Background: High plasma adiponectin levels are associated with diabetic
nephropathy (DN). T-cadherin gene (CDH13) variants have been shown to be
associated with adiponectin levels. We investigated associations between allelic
variations of CDH13 and DN in subjects with type 1 diabetes. Methods: Two CDH13
polymorphisms were analysed in 1297 Caucasian subjects with type 1 diabetes from
the 'Survival Genetic Nephropathy' (SURGENE) (n = 340, 10-year follow-up),
'Genesis France-Belgium' (GENESIS) (n = 501, 5-year follow-up for n = 462) and
'Genetique de la Nephropathie Diabetique' (GENEDIAB) (n = 456, 9-year follow-up
for n = 283) cohorts. Adiponectin levels were measured in plasma samples from
GENESIS and GENEDIAB cohorts. Results: Pooled analysis of GENEDIAB and GENESIS
studies showed that baseline plasma adiponectin levels were higher in subjects
with established/advanced DN at inclusion (P < 0.0001) and in subjects who
developed end-stage renal disease (ESRD) at follow-up (P < 0.0001). The minor
allele of rs3865188 was associated with lower adiponectin levels (P = 0.006).
rs11646213 [odds ratio (OR) 1.47; 95% confidence interval (CI) 1.18-1.85; P =
0.0009] and rs3865188 (OR 0.71; 95% CI 0.57-0.90; P = 0.004) were associated with
baseline prevalence of established/advanced DN. These polymorphisms were also
associated with the risk of ESRD (0.006 < P < 0.03). The association between
rs11646213 (but not rs3865188) and renal function remained significant after
adjustment for plasma adiponectin. In SURGENE, rs11646213 [hazard ratio (HR)
1.69; 95% CI 1.01-2.71; P = 0.04] and rs3865188 (HR 0.74; 95% CI 0.55-0.99; P =
0.04) were associated with risk of renal events (defined as progression to more
severe DN stages). Conclusions: Plasma adiponectin levels are associated with the
prevalence of DN and the incidence of ESRD in patients with type 1 diabetes.
CDH13 polymorphisms are also associated with the prevalence and incidence of DN,
and with the incidence of ESRD in these patients. The association between CDH13
and DN may be due to pleiotropic effects, both dependent and independent of
plasma adiponectin levels.
PMID- 28499018
TI - Intracystic interferon-alpha in pediatric craniopharyngioma patients: an
international multicenter assessment on behalf of SIOPE and ISPN.
AB - Background: Craniopharyngiomas are frequent hypothalamo-pituitary tumors in
children, presenting predominantly as cystic lesions. Morbidity from conventional
treatment has focused attention on intracystic drug delivery, hypothesized to
cause fewer clinical consequences. However, the efficacy of intracystic therapy
remains unclear. We report the retrospective experiences of several global
centers using intracystic interferon-alpha. Methods: European Societe
Internationale d'Oncologie Pediatrique and International Society for Pediatric
Neurosurgery centers were contacted to submit a datasheet capturing pediatric
patients with cystic craniopharyngiomas who had received intracystic interferon
alpha. Patient demographics, administration schedules, adverse events, and
outcomes were obtained. Progression was clinical or radiological (cyst
reaccumulation, novel cysts, or solid growth). Results: Fifty-six children
(median age, 6.3 y) from 21 international centers were identified. Median follow
up from diagnosis was 5.1 years (0.3-17.7 y). Lesions were cystic (n = 22; 39%)
or cystic/solid (n = 34; 61%). Previous progression was treated in 43 (77%)
patients before interferon use. In such cases, further progression was delayed by
intracystic interferon compared with the preceding therapy for cystic lesions (P
= 0.0005). Few significant attributable side effects were reported. Progression
post interferon occurred in 42 patients (median 14 mo; 0-8 y), while the
estimated median time to definitive therapy post interferon was 5.8 (1.8-9.7)
years. Conclusions: Intracystic interferon-alpha can delay disease progression
and potentially offer a protracted time to definitive surgery or radiotherapy in
pediatric cystic craniopharyngioma, yet demonstrates a favorable toxicity profile
compared with other therapeutic modalities-important factors for this developing
age group. A prospective, randomized international clinical trial assessment is
warranted.
PMID- 28499021
TI - Protein-only RNase P function in Escherichia coli: viability, processing defects
and differences between PRORP isoenzymes.
AB - The RNase P family comprises structurally diverse endoribonucleases ranging from
complex ribonucleoproteins to single polypeptides. We show that the organellar
(AtPRORP1) and the two nuclear (AtPRORP2,3) single-polypeptide RNase P isoenzymes
from Arabidopsis thaliana confer viability to Escherichia coli cells with a
lethal knockdown of its endogenous RNA-based RNase P. RNA-Seq revealed that
AtPRORP1, compared with bacterial RNase P or AtPRORP3, cleaves several precursor
tRNAs (pre-tRNAs) aberrantly in E. coli. Aberrant cleavage by AtPRORP1 was mainly
observed for pre-tRNAs that can form short acceptor-stem extensions involving G:C
base pairs, including tRNAAsp(GUC), tRNASer(CGA) and tRNAHis. However, both
AtPRORP1 and 3 were defective in processing of E. coli pre-tRNASec carrying an
acceptor stem expanded by three G:C base pairs. Instead, pre-tRNASec was
degraded, suggesting that tRNASec is dispensable for E. coli under laboratory
conditions. AtPRORP1, 2 and 3 are also essentially unable to process the primary
transcript of 4.5S RNA, a hairpin-like non-tRNA substrate processed by E. coli
RNase P, indicating that PRORP enzymes have a narrower, more tRNA-centric
substrate spectrum than bacterial RNA-based RNase P enzymes. The cells' viability
also suggests that the essential function of the signal recognition particle can
be maintained with a 5?-extended 4.5S RNA.
PMID- 28499023
TI - The Chilean Recluse Spider (Araneae: Sicariidae) Displays Behavioral Responses to
Conspecific Odors, but Not to Several General Odorants.
AB - Spiders of the family Sicariidae pose a serious threat to affected populations,
and Loxosceles laeta (Nicolet) is considered the most venomous species.
Development of nontoxic olfaction-based spider repellents or traps is hindered by
a current lack of knowledge regarding olfactory system function in arachnids. In
the present study, general plant odorants and conspecific odors were tested for
behavioral responses in L. laeta. Although general odorants triggered neither
attraction nor aversion, conspecific odor of the opposite sex caused aversion in
females, and attraction in males. These results support the presence of a
specific olfactory system for the detection of conspecifics in L. laeta, but
suggest the absence of a broadly tuned system for general odorant detection in
this species.
PMID- 28499024
TI - Welcome Editorial by the new NDT Editor-in-Chief.
PMID- 28499022
TI - Quantitative imaging biomarkers for risk stratification of patients with
recurrent glioblastoma treated with bevacizumab.
AB - Background: Anti-angiogenic therapy with bevacizumab is the most widely used
treatment option for recurrent glioblastoma, but therapeutic response varies
substantially and effective biomarkers for patient selection are not available.
To this end, we determine whether novel quantitative radiomic strategies on the
basis of MRI have the potential to noninvasively stratify survival and
progression in this patient population. Methods: In an initial cohort of 126
patients, we identified a distinct set of features representative of the
radiographic phenotype on baseline (pretreatment) MRI. These selected features
were evaluated on a second cohort of 165 patients from the multicenter BRAIN
trial with prospectively acquired clinical and imaging data. Features were
evaluated in terms of prognostic value for overall survival (OS), progression
free survival (PFS), and progression within 3, 6, and 9 months using baseline
imaging and first follow-up imaging at 6 weeks posttreatment initiation. Results:
Multivariable analysis of features derived at baseline imaging resulted in
significant stratification of OS (hazard ratio [HR] = 2.5; log-rank P = 0.001)
and PFS (HR = 4.5; log-rank P = 2.1 * 10-5) in validation data. These
stratifications were stronger compared with clinical or volumetric covariates
(permutation test false discovery rate [FDR] <0.05). Univariable analysis of a
prognostic textural heterogeneity feature (information correlation) derived from
postcontrast T1-weighted imaging revealed significantly higher scores for
patients who progressed within 3 months (Wilcoxon test P = 8.8 * 10-8).
Generally, features derived from postcontrast T1-weighted imaging yielded higher
prognostic power compared with precontrast enhancing T2-weighted imaging.
Conclusion: Radiomics provides prognostic value for survival and progression in
patients with recurrent glioblastoma receiving bevacizumab treatment. These
results could lead to the development of quantitative pretreatment biomarkers to
predict benefit from bevacizumab using standard of care imaging.
PMID- 28499026
TI - Opponent's comments.
PMID- 28499025
TI - Pro: Risk scores for chronic kidney disease progression are robust, powerful and
ready for implementation.
AB - Accurate risk prediction for chronic kidney disease (CKD) progression can inform
the patient-provider dialogue, and provide actionable thresholds for key clinical
decisions. In 2011, we developed the kidney failure risk equations (KFREs) to
predict the risk of kidney failure requiring dialysis or transplant in patients
with CKD. Subsequently, the KFREs have been extensively validated, and have now
been proven accurate in multiple continents, ethnicities and disease-specific
subpopulations. They can discriminate progressors from non-progressors, and are
well calibrated and easy to use. We believe that current and future studies
should now focus on clinical implementation of the KFREs, through quality
improvement initiatives and cluster randomized trials. A risk-based care paradigm
for CKD care can be achieved through knowledge translation and implementation
research.
PMID- 28499027
TI - Farewell Editorial.
PMID- 28499028
TI - Con: Most clinical risk scores are useless.
AB - While developing prediction models has become quite popular both in nephrology
and in medicine in general, most models have not been implemented in clinical
practice on a larger scale. This should be no surprise, as the majority of
published models has been shown to be poorly reported and often developed using
inappropriate methods. The main problems identified relate to either using too
few candidate predictors (based on univariable P < 0.05) or too many (for the
number of events), resulting in poorly performing prediction models. Guidelines
on how to develop and test a prediction model all stress the importance of
external validation to test discrimination and calibration in other populations,
as prediction models usually perform less well in new subjects. However, external
validity has not often been tested for prediction models in renal patients.
Moreover, impact studies showing improved clinical outcomes when using a
prediction model in routine clinical practice have been reported rarely. By and
large, notwithstanding a few notable exceptions like the kidney failure risk
equation prediction model, most models have not been validated externally or are
at best inadequately reported, preventing them from be used in clinical practice.
Therefore, we recommend researchers to spend more energy on validation and
assessing the impact of existing models, instead of merely developing more models
that will most likely never be used in clinical practice as well.
PMID- 28499029
TI - Opponent's comments.
PMID- 28499030
TI - Moderator's view: Predictive models: a prelude to precision nephrology.
AB - Appropriate diagnosis is fundamental in medicine because it sets the basis for
the prediction of disease outcome at the single patient level (prognosis) and
decisions regarding the most appropriate therapy. However, given the large series
of social, clinical and biological factors that determine the likelihood of an
individual's future outcome, prognosis only partly depends on diagnosis and
aetiology and treatment is not decided solely on the basis of the underlying
diagnosis. This issue is crucial in multifactorial diseases like atherosclerosis,
where the use of statins has now shifted from 'treating hypercholesterolaemia' to
'treating the risk of adverse cardiovascular events'. Approaches that take due
account of prognosis limit the lingering risk of over-diagnosis and maximize the
value of prognostic information in the clinical decision process. In the
nephrology realm, the application of a well-validated risk equation for kidney
failure in Canada led to a 35% reduction in new referrals. Prognostic models
based on simple clinical data extractable from clinical files have recently been
developed to predict all-cause and cardiovascular mortality in end-stage kidney
disease patients. However, research on predictive models in renal diseases
remains suboptimal and non-accounting for competing events and measurement
errors, and a lack of calibration analyses and external validation are common
fallacies in currently available studies. More focus on this blossoming research
area is desirable. The nephrology community may now start to apply the best
validated risk scores and further test their potential usefulness in chronic
kidney disease patients in diverse clinical situations and geographical areas.
PMID- 28499031
TI - Primary echinococcus infection of the heart: a rare type of cystic
echinococcosis.
PMID- 28499032
TI - Development of a New Tool for Systematic Observation of Nursing Home Resident and
Staff Engagement and Relationship.
AB - Purpose of Study: To develop a structured observational tool, the Resident
centered Assessment of Interactions with Staff and Engagement tool (RAISE), to
measure 2 critical, multi-faceted, organizational-level aspects of person
centered care (PCC) in nursing homes: (a) resident engagement and (b) the quality
and frequency of staff-resident interactions. Design and Methods: In this multi
method psychometric development study, we conducted (a) 120 hr of ethnographic
observations in one nursing home and (b) a targeted literature review to enable
construct development. Two constructs for which no current structured observation
measures existed emerged from this phase: nursing home resident-staff engagement
and interaction. We developed the preliminary RAISE to measure these constructs
and used the tool in 8 nursing homes at an average of 16 times. We conducted 8
iterative psychometric testing and refinement cycles with multi-disciplinary
research team members. Each cycle consisted of observations using the draft tool,
results review, and tool modification. Results: The final RAISE included a set of
coding rules and procedures enabling simultaneously efficient, non-reactive, and
representative quantitative measurement of the interaction and engagement
components of nursing home life for staff and residents. It comprised 8
observational variables, each represented by extensive numeric codes. Raters
achieved adequate to high reliability with all variables. There is preliminary
evidence of face and construct validity via expert panel review. Implications:
The RAISE represents a valuable step forward in the measurement of PCC, providing
objective, reliable data based on systematic observation.
PMID- 28499033
TI - Large-scale recoding of a bacterial genome by iterative recombineering of
synthetic DNA.
AB - The ability to rewrite large stretches of genomic DNA enables the creation of new
organisms with customized functions. However, few methods currently exist for
accumulating such widespread genomic changes in a single organism. In this study,
we demonstrate a rapid approach for rewriting bacterial genomes with modified
synthetic DNA. We recode 200 kb of the Salmonella typhimurium LT2 genome through
a process we term SIRCAS (stepwise integration of rolling circle amplified
segments), towards constructing an attenuated and genetically isolated bacterial
chassis. The SIRCAS process involves direct iterative recombineering of 10-25 kb
synthetic DNA constructs which are assembled in yeast and amplified by rolling
circle amplification. Using SIRCAS, we create a Salmonella with 1557 synonymous
leucine codon replacements across 176 genes, the largest number of cumulative
recoding changes in a single bacterial strain to date. We demonstrate
reproducibility over sixteen two-day cycles of integration and parallelization
for hierarchical construction of a synthetic genome by conjugation. The resulting
recoded strain grows at a similar rate to the wild-type strain and does not
exhibit any major growth defects. This work is the first instance of synthetic
bacterial recoding beyond the Escherichia coli genome, and reveals that
Salmonella is remarkably amenable to genome-scale modification.
PMID- 28499034
TI - Functional disability and its predictors in systemic sclerosis: a study from the
DeSScipher project within the EUSTAR group.
AB - Objectives: The multisystem manifestations of SSc can greatly impact patients'
quality of life. The aim of this study was to identify factors associated with
disability in SSc. Methods: SSc patients from the prospective DeSScipher cohort
who had completed the scleroderma health assessment questionnaire (SHAQ), a
disability score that combines the health assessment questionnaire and five
visual analogue scales, were included in this analysis. The effect of factors
possibly associated with disability was analysed with multiple linear
regressions. Results: The mean SHAQ and HAQ scores of the 944 patients included
were 0.87 (s.d. = 0.66) and 0.92 (s.d. = 0.78); 59% of the patients were in the
mild to moderate difficulty SHAQ category (0 ? SHAQ < 1), 34% in the moderate to
severe disability category (1 ? SHAQ < 2) and 7% in the severe to very severe
disability category (2 ? SHAQ ? 3). The means of the visual analogue scales
scores were in order of magnitude: overall disease severity (37 mm), RP (31 mm),
pulmonary symptoms (24 mm), gastrointestinal symptoms (20 mm) and digital ulcers
(19 mm). In multiple regression, the main factors associated with high SHAQ
scores were the presence of dyspnoea [modified New York Heart Association (NYHA)
class IV (regression coefficient B = 0.62), modified NYHA class III (B = 0.53)
and modified NYHA class II (B = 0.21; all vs modified NYHA class I)], FM (B =
0.37), muscle weakness (B = 0.27), digital ulcers (B = 0.20) and gastrointestinal
symptoms (oesophageal symptoms, B = 0.16; stomach symptoms, B = 0.15; intestinal
symptoms, B = 0.15). Conclusion: SSc patients perceive dyspnoea, pain, digital
ulcers, muscle weakness and gastrointestinal symptoms as the main factors driving
their level of disability, unlike physicians who emphasize objective measures of
disability.
PMID- 28499035
TI - Genetic and Biological Characterization of Four Nucleopolyhedrovirus Isolates
Collected in Mexico for the Control of Spodoptera exigua (Lepidoptera:
Noctuidae).
AB - This study describes four multiple nucleocapsid nucleopolyhedrovirus isolates
recovered from infected larvae of beet armyworm, Spodoptera exigua (Hubner)
(Lepidoptera: Noctuidae), on crops in two different geographical regions of
Mexico. Molecular and biological characterization was compared with characterized
S. exigua multiple nucleopolyhedrovirus (SeMNPV) isolates from the United States
(SeUS1 and SeUS2) and Spain (SeSP2). Restriction endonuclease analysis of viral
DNA confirmed that all Mexican isolates were SeMNPV isolates, but molecular
differences between the Mexican and the reference isolates were detected using
PCR combined with restriction fragment length polymorphism (RFLP). Amplification
of the variable region V01 combined with RFLP distinguished the two Mexican
isolates, SeSLP6 and SeSIN6. BglII digestions showed that the majority of the
isolates contained submolar bands, indicating the presence of genetic
heterogeneity. Amplification of the variable regions V04 and V05 distinguished
between American and the Spanish isolates. Biological characterization was
performed against two laboratory colonies of S. exigua, one from Mexico, and
another from Switzerland. Insects from the Mexican colony were less susceptible
to infection than insects from Se-Swiss colony. In the Se-Mex colony, SeSP2 was
the most pathogenic isolate followed by SeSIN6, although their virulence was
similar to most of the isolates tested. In Se-Swiss colony, similar LD50 values
were observed for the five isolates, although the virulence was higher for the
SeSLP6 isolate, which also had the highest OB (occlusion body) yield. We conclude
that the Mexican isolates SeSIN6 and SeSLP6 possess insecticidal traits of value
for the development of biopesticides for the control of populations of S. exigua.
PMID- 28499036
TI - Potential of a Northern Population of Aedes vexans (Diptera: Culicidae) to
Transmit Zika Virus.
AB - Zika virus is an emerging arbovirus of humans in the western hemisphere. With its
potential spread into new geographical areas, it is important to define the
vector competence of native mosquito species. We tested the vector competency of
Aedes vexans (Meigen) from the Lake Agassiz Plain of northwestern Minnesota and
northeastern North Dakota. Aedes aegypti (L.) was used as a positive control for
comparison. Mosquitoes were fed blood containing Zika virus and 2 wk later were
tested for viral infection and dissemination. Aedes vexans (n = 60) were
susceptible to midgut infection (28% infection rate) but displayed a fairly
restrictive midgut escape barrier (3% dissemination rate). Cofed Ae. aegypti (n =
22) displayed significantly higher rates of midgut infection (61%) and
dissemination (22%). To test virus transmission, mosquitoes were inoculated with
virus and 16-17 d later, tested for their ability to transmit virus into fluid
filled capillary tubes. Unexpectedly, the transmission rate was significantly
higher for Ae. vexans (34%, n = 47) than for Ae. aegypti (5%, n = 22). The
overall transmission potential for Ae. vexans to transmit Zika virus was 1%.
Because of its wide geographic distribution, often extreme abundance, and
aggressive human biting activity, Ae. vexans could serve as a potential vector
for Zika virus in northern latitudes where the conventional vectors, Ae. aegypti
and Ae. albopictus Skuse, cannot survive. However, Zika virus is a primate virus
and humans are the only amplifying host species in northern latitudes. To serve
as a vector of Zika virus, Ae. vexans must feed repeatedly on humans. Defining
the propensity of Ae. vexans to feed repeatedly on humans will be key to
understanding its role as a potential vector of Zika virus.
PMID- 28499037
TI - Ball with hair: modular functionalization of highly stable G-quadruplex DNA nano
scaffolds through N2-guanine modification.
AB - Functionalized nanoparticles have seen valuable applications, particularly in the
delivery of therapeutic and diagnostic agents in biological systems. However, the
manufacturing of such nano-scale systems with the consistency required for
biological application can be challenging, as variation in size and shape have
large influences in nanoparticle behavior in vivo. We report on the development
of a versatile nano-scaffold based on the modular functionalization of a DNA G
quadruplex. DNA sequences are functionalized in a modular fashion using well
established phosphoramidite chemical synthesis with nucleotides containing
modification of the amino (N2) position of the guanine base. In physiological
conditions, these sequences fold into well-defined G-quadruplex structures. The
resulting DNA nano-scaffolds are thermally stable, consistent in size, and
functionalized in a manner that allows for control over the density and relative
orientation of functional chemistries on the nano-scaffold surface. Various
chemistries including small modifications (N2-methyl-guanine), bulky aromatic
modifications (N2-benzyl-guanine), and long chain-like modifications (N2-6-amino
hexyl-guanine) are tested and are found to be generally compatible with G
quadruplex formation. Furthermore, these modifications stabilize the G-quadruplex
scaffold by 2.0-13.3 degrees C per modification in the melting temperature, with
concurrent modifications producing extremely stable nano-scaffolds. We
demonstrate the potential of this approach by functionalizing nano-scaffolds for
use within the biotin-avidin conjugation approach.
PMID- 28499039
TI - Scrofula.
PMID- 28499038
TI - Functional characterization and architecture of recombinant yeast SWR1 histone
exchange complex.
AB - We have prepared recombinant fourteen subunit yeast SWR1 complex from insect
cells using a modified MultiBac system. The 1.07 MDa recombinant protein complex
has histone-exchange activity. Full exchange activity is realized with a single
SWR1 complex bound to a nucleosome. We also prepared mutant complexes that lack a
variety of subunits or combinations of subunits and these start to reveal roles
for some of these subunits as well as indicating interactions between them in the
full complex. Complexes containing a series of N-terminally and C-terminally
truncated Swr1 subunits reveal further details about interactions between
subunits as well as their binding sites on the Swr1 subunit. Finally, we present
electron microscopy studies revealing the dynamic nature of the complex and a 21
A resolution reconstruction of the intact complex provides details not apparent
in previously reported structures, including a large central cavity of sufficient
size to accommodate a nucleosome.
PMID- 28499040
TI - Evolving gene banks: improving diverse populations of crop and exotic germplasm
with optimal contribution selection.
AB - We simulated pre-breeding in evolving gene banks - populations of exotic and crop
types undergoing optimal contribution selection for long-term genetic gain and
management of population genetic diversity. The founder population was based on
crosses between elite crop varieties and exotic lines of field pea (Pisum
sativum) from the primary genepool, and was subjected to 30 cycles of recurrent
selection for an economic index composed of four traits with low heritability:
black spot resistance, flowering time and stem strength (measured on single
plants), and grain yield (measured on whole plots). We compared a small
population with low selection pressure, a large population with high selection
pressure, and a large population with moderate selection pressure. Single seed
descent was compared with S0-derived recurrent selection. Optimal contribution
selection achieved higher index and lower population coancestry than truncation
selection, which reached a plateau in index improvement after 40 years in the
large population with high selection pressure. With optimal contribution
selection, index doubled in 38 years in the small population with low selection
pressure and 27-28 years in the large population with moderate selection
pressure. Single seed descent increased the rate of improvement in index per
cycle but also increased cycle time.
PMID- 28499041
TI - Nature's pulse power: legumes, food security and climate change.
PMID- 28499042
TI - Proteomic analysis reveals changes in carbohydrate and protein metabolism
associated with broiler breast myopathy.
AB - White Striping (WS) and Woody Breast (WB) are 2 conditions that adversely affect
consumer acceptance as well as quality of poultry meat and meat products. Both WS
and WB are characterized with degenerative myopathic changes. Previous studies
showed that WS and WB in broiler fillets could result in higher ultimate pH,
increased drip loss, and decreased marinade uptake. The main objective of the
present study was to compare the proteomic profiles of muscle tissue (n = 5 per
group) with either NORM (no or few minor myopathic lesions) or SEV (with severe
myopathic changes). Proteins were extracted from these samples and analyzed using
a hybrid LTQ-OrbitrapXL mass spectrometer (LC-MS/MS). Over 800 proteins were
identified in the muscle samples, among which 141 demonstrated differential (P <
0.05) expression between NORM and SEV. The set of differentially (P < 0.05)
expressed proteins was uploaded to Ingenuity Pathway Analysis(r) (IPA) software
to determine the associated biological networks and pathways. The IPA analysis
showed that eukaryotic initiation factor-2 (eIF-2) signaling, mechanistic target
of rapamycin (mTOR) signaling, as well as regulation of eIF4 and p70S6K signaling
were the major canonical pathways up-regulated (P < 0.05) in SEV muscle compared
to NORM. The up-regulation of these pathways indicate an increase in protein
synthesis which could be part of the rapid growth as well as cellular stress
associated with ongoing muscle degeneration and the attempt to repair tissue
damage in SEV birds. Furthermore, IPA analysis revealed that glycolysis and
gluconeogenesis were the major down-regulated (P < 0.05) canonical pathways in
SEV with respect to NORM muscle. Down-regulation of these pathways could be the
reason for higher ultimate pH seen in SEV muscle samples indicating reduced
glycolytic potential. In conclusion, comparison of proteomic profiles of NORM and
SEV muscle samples showed differences in protein profile which explains some of
the observed differences in meat quality parameters. Future studies based on
these differences could provide valuable insights into various cellular changes
and identification of biomarkers related to WS and WB.
PMID- 28499043
TI - Bioethics and Transhumanism.
AB - Transhumanism is a "technoprogressive" socio-political and intellectual movement
that advocates for the use of technology in order to transform the human organism
radically, with the ultimate goal of becoming "posthuman." To this end,
transhumanists focus on and encourage the use of new and emerging technologies,
such as genetic engineering and brain-machine interfaces. In support of their
vision for humanity, and as a way of reassuring those "bioconservatives" who may
balk at the radical nature of that vision, transhumanists claim common ground
with a number of esteemed thinkers and traditions, from the ancient philosophy of
Plato and Aristotle to the postmodern philosophy of Nietzsche. It is crucially
important to give proper scholarly attention to transhumanism now, not only
because of its recent and ongoing rise as a cultural and political force (and the
concomitant potential ramifications for bioethical discourse and public policy),
but because of the imminence of major breakthroughs in the kinds of technologies
that transhumanism focuses on. Thus, the articles in this issue of The Journal of
Medicine and Philosophy are either explicitly about transhumanism or are on
topics, such as the ethics of germline engineering and criteria for personhood,
that are directly relevant to the debate between transhumanists (and
technoprogressives more broadly) and bioconservatives.
PMID- 28499044
TI - Determinants of decline of renal function in treated hypertensive patients: the
Campania Salute Network.
AB - Background: Hypertension is a leading cause of chronic kidney disease (CKD) and a
decrease in glomerular filtration rate (GFR) is associated with a higher
prevalence of hypertension and an increased proportion of suboptimal blood
pressure (BP) control. Methods: To investigate characteristics associated with
GFR decline, we selected 4539 hypertensive patients from the Campania Salute
Network (mean age 53 +/- 11 years) with at least 3 years of follow-up (FU) and no
more than Stage III CKD. GFR was calculated at baseline and at the last available
visit using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
equation. GFR decline was defined as a >=30% decrease from initial GFR for
patients in Stage III CKD or by a composite >=30% decrease from baseline and a
final value of <60 for those < with Stage III or higher CKD. Results: At a mean
FU of 7.5 years, 432 patients (10%) presented with GFR decline. Those patients
were older, more likely to be diabetic, with lower GFR and ejection fraction,
higher systolic and lower diastolic BP and higher left ventricular (LV) mass and
relative wall thickness at baseline; during FU, patients with GFR decline
exhibited higher systolic BP, took more drugs and developed more atrial
fibrillation (all P < 0.02). The probability of GFR decline was independently
associated with older age, prevalent diabetes, baseline lower GFR, higher
systolic BP during FU, FU duration, increased LV mass and incident AF with no
impact from antihypertensive and antiplatelet medications. Conclusions: During
antihypertensive therapy, kidney function declines in patients with initially
lower GFR, increased LV mass and suboptimal BP control during FU.
PMID- 28499045
TI - Challenges Facing Today's Families and Why Social Work Matters.
PMID- 28499046
TI - Letter to the Editor: Very Late Reactivation of Retinopathy of Prematurity After
Monotherapy With Intravitreal Bevacizumab.
PMID- 28499047
TI - Current Treatment Options for the Management of Vitreomacular Traction.
PMID- 28499048
TI - Three Different Optical Coherence Tomography Angiography Measurement Methods for
Assessing Capillary Density Changes in Diabetic Retinopathy.
AB - BACKGROUND AND OBJECTIVE: To compare capillary density (CD) changes assessed by
optical coherence tomography angiography (OCTA) during diabetic retinopathy (DR)
progression using three previously published methods: binarization,
skeletonization, and automated flow density (AFD). PATIENTS AND METHODS:
Retrospective study of 98 eyes of 74 patients with diabetes and 18 control eyes
imaged using OCTA. The macular CD at each stage of DR was assessed using the
three methods and were compared to control eyes. RESULTS: AFD was the only method
that detected differences between controls and severe nonproliferative DR eyes.
The three methods showed a significant difference in CD between controls and eyes
with proliferative DR, except for the "fovea" area. CONCLUSION: Only one of the
three methods allowed for the detection of changes from the normal capillary
density as early as at the "severe nonproliferative DR" stage due to several
refinements from the basic technique. [Ophthalmic Surg Lasers Imaging Retina.
2017;48:378-384.].
PMID- 28499049
TI - Quantitative Comparison of Swept-Source and Spectral-Domain OCT Angiography in
Healthy Eyes.
AB - BACKGROUND AND OBJECTIVE: To compare macular vessel density (VD) and foveal
avascular zone (FAZ) area in healthy individuals using two different optical
coherence tomography angiography (OCTA) devices. PATIENTS AND METHODS: In this
prospective, comparative study, 25 eyes of 14 healthy subjects underwent fovea
centered 3 mm * 3 mm OCTA-imaging using the Triton (Topcon, Tokyo, Japan) and RS
3000 (Nidek, Gamagori, Japan) OCTA devices. Superficial and deep retinal layers
(SRL/DRL) and FAZ were manually graded after threshold standardization to
determine macular VD and area of the FAZ. RESULTS: The mean difference in the VD
between the two devices was 0.105 and 0.096, and the coefficient of variation
(CV) was 19.59% and 16.90% for the SRL and DRL, respectively. After
skeletonization of vessels to remove variation related to vessel width, the mean
difference was 0.174 mm-1 and 0.516 mm-1, and the CV was 3.49% and 1.07% for SRL
and DRL, respectively. The mean difference of FAZ area was 0.001 mm2 and 0.010
mm2 in the SRL and DRL, respectively, and the CV was 2.17% and 5.74% for the SRL
and DRL, respectively. CONCLUSION: Macular VD using skeletonized mapping and FAZ
area in SRL and DRL were statistically similar between the two devices,
demonstrating a possible comparison of quantitative values between different OCTA
devices. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:385-391.].
PMID- 28499050
TI - Swept-Source OCT Visualization of Macular Hole Closure in Gas-Filled Eyes.
AB - BACKGROUND AND OBJECTIVE: To assess the utility of swept-source optical coherence
tomography (SS-OCT) in visualizing macular hole (MH) closure through gas-filled
eyes on postoperative day (POD) 1 using a dual scanning protocol. PATIENTS AND
METHODS: We examined 30 consecutive patients with full-thickness MH who underwent
standard vitrectomy with SF6 (25%) gas tamponade between July 2015 and April
2016. SS-OCT imaging was performed using horizontal raster and 16-line radial
scans with manual delicate focusing to evaluate MH closure status. RESULTS: On
POD1, optically clear images with visualization of all retinal layers at the
fovea were obtained in 80% of eyes, of which 71% achieved complete MH closure.
Reasons for unsuccessful imaging included: hyphema (two eyes), dense cataract
(two eyes), and gas meniscus interference (two eyes). CONCLUSION: SS-OCT with
dual scanning protocol and manual delicate focusing enabled consistent early
visualization of foveal architecture for assessment of MH closure through gas
filled eyes. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:392-398.].
PMID- 28499051
TI - Safety and Efficacy of Ziv-Aflibercept in the Treatment of Refractory Diabetic
Macular Edema.
AB - BACKGROUND AND OBJECTIVE: To evaluate the safety and efficacy of ziv-aflibercept
(Zaltrap; Sanofi-Aventis, Bridgewater, NJ/Regeneron Pharmaceuticals, Tarrytown,
NY) in the treatment of refractory diabetic macular edema (DME). PATIENTS AND
METHODS: Retrospective case series looking at the safety of ziv-aflibercept in
patients with DME refractory to previous anti-vascular endothelial growth factor
(VEGF) therapy. Detailed ophthalmologic examination, best-corrected visual
acuity, and optical coherence tomography measurements were performed pre-switch,
as well as at each monthly follow-up visit. RESULTS: The study included 34 eyes
of 26 patients. The mean number of ziv-aflibercept injections post-switch was
2.03 injections. Visual acuity improved from a mean of 0.63 logMAR pre-switch to
0.51 logMAR after the first visit and 0.46 logMAR after the second visit post
switch (P < .084). Macular thickness improved from a mean of 513.79 MUm to 411.79
MUm (P = .006) on the first visit and 426.76 MUm (P = .029) after the second
visit post-switch. No adverse ocular or systemic side effects were reported on
any of the follow visits. CONCLUSION: Ziv-aflibercept appears to be safe and
effective in patients with refractory DME previously treated with other anti-VEGF
agents in the short term. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:399
405.].
PMID- 28499052
TI - Outcomes of 27-Gauge Vitrectomy-Assisted Choroidal and Subretinal Biopsy.
AB - BACKGROUND AND OBJECTIVE: To report the initial experience of 27-gauge vitrectomy
assisted choroidal and subretinal biopsy PATIENTS AND METHODS: Retrospective,
interventional case series. Eighteen eyes of 18 patients undergoing 27-gauge
vitrectomy-assisted choroidal (n = 16) or subretinal biopsy (n = 2). Clinical and
lesion characteristics, cytopathology, histology, gene expression profiling
(GEP), visual acuity (VA), complications including vitreous hemorrhage (VH),
development of rhegmatogenous retinal detachment (RD), and need for additional
surgeries were analyzed. RESULTS: Indications were choroidal melanoma (n = 10),
indeterminate choroidal (n = 5), and subretinal lesions (n = 3). Mean lesion
height was 3.33 mm +/- 1.55 mm (range: 0.80 mm to 6.75 mm) and largest diameter
was 8.63 mm +/- 4.14 mm (range: 3 mm to 15.5 mm). Mean number of intralesional
biopsy passes required was 1.76 +/- 0.83 (range: one to four). During a mean
follow-up of 7.4 months +/- 2.7 months (range: 4 months to 14 months), VA was
unchanged (0.5 logMAR +/- 0.6 logMAR vs. 0.7 logMAR +/- 0.84 logMAR; P = .07).
Pathologic diagnosis was obtained in 16 of 18 eyes (88.9%), and GEP data were
collected for all 11 choroidal melanomas. Post-biopsy VH occurred in 13 of 18
eyes (72.2%) and was severe enough to require a concurrent limited vitrectomy in
six eyes (33.3%). These eyes had a greater lesion height compared to eyes not
requiring a vitrectomy (4.08 mm +/- 1.68 mm vs. 2.76 mm +/- 1.43 mm; P = .04). A
rhegmatogenous RD requiring repeat surgery developed in two of 18 eyes (11.1%).
CONCLUSION: The authors concluded that 27-gauge vitrectomy-assisted choroidal and
subretinal biopsy established a diagnosis in 88.9% of eyes in lesions 0.8 mm or
larger. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:406-415.].
PMID- 28499053
TI - A Modified Perfluoro-n-octane-Assisted Autologous Internal Limiting Membrane
Transplant for Failed Macular Hole Reintervention: A Case Series.
AB - The authors describe a modified perfluoro-n-octane (PFO)-assisted autologous
internal limiting membrane (ILM) transplantation technique for macular hole (MH)
reintervention and present results from a series of 11 patients. The authors
harvested a free ILM flap and transplanted it into the MH under a PFO bubble. The
time at which PFO is injected, the extent of coverage of PFO, and the sequence of
fluid-air exchange (FAE) are crucial to overcome previously described technical
difficulties of relieving the flap from forceps, stabilizing the flap into the
MH, and prevention of flap dislodgement during FAE. A successful U-shaped closure
was observed in 10 of 11 cases (90.9%). One case (9.1%) showed flat open closure.
The postoperative visual gain was statistically significant (P = .01).
[Ophthalmic Surg Lasers Imaging Retina. 2017;48:416-420.].
PMID- 28499054
TI - Manual Removal of Intraocular Lens Silicone Oil Droplets and Dystrophic
Calcifications Using a Nitinol Loop: A Case Series.
AB - Deposition of dystrophic calcifications on the posterior surface of silicone
intraocular lenses (IOLs) has been reported in patients with asteroid hyalosis.
Accumulation of silicone oil droplets on the posterior surface of silicone IOLs
in silicone-filled eyes has also been reported. Recently, a novel technique to
manually remove dystrophic calcifications using a nickel titanium loop (Finesse
Flex Loop; Alcon, Fort Worth, TX) was described, obviating the need for IOL
exchange. Here, the authors report their outcomes with this technique in five
eyes with IOL dystrophic calcifications as well as one eye with IOL silicone oil
droplet accumulation. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:422-426.].
PMID- 28499055
TI - Sequential Sterile Intraocular Inflammation Associated With Consecutive
Intravitreal Injections of Aflibercept and Ranibizumab.
AB - The authors report the unique response of two patients treated for cystoid
macular edema (CME) secondary to central retinal vein occlusion (CRVO) who
developed sequential episodes of likely sterile inflammatory responses following
separate intravitreal injections of aflibercept (Eylea; Regeneron, Tarrytown, NY)
and ranibizumab (Lucentis; Genentech, South San Francisco, CA) despite multiple
previous uneventful injections for CME secondary to CRVO. Following the twenty
fifth aflibercept and seventh ranibizumab injection, two patients developed an
acute inflammatory response, which was treated empirically with intravitreal
antibiotics and topical and oral steroids (in Case 2). After an 8- to 10-week
hiatus, they were switched over to ranibizumab and aflibercept, respectively,
following which they developed a second episode of intraocular inflammation,
treated similarly. Vitreous culture in one and aqueous culture in the other were
deemed to represent contamination. Sterile intraocular inflammation, a known risk
following injection with either aflibercept or ranibizumab, may develop
sequentially in the same patient despite switching the drug. [Ophthalmic Surg
Lasers Imaging Retina. 2017;48:428-431.].
PMID- 28499056
TI - Recurrent Macular Detachment Due to Occult Retinal Break in a Patient With Optic
Disc Pit.
AB - Serous macular detachment occurs in nearly 50% of eyes with optic disc pit. These
macular detachments have been historically difficult to treat. The authors report
a case of macular retinal detachment due to an occult juxtapapillary retinal
break in a patient with optic disc pit refractory to prior treatments. This case
demonstrates that a presumed serous detachment associated with an optic disc pit
may have a rhegmatogenous etiology. [Ophthalmic Surg Lasers Imaging Retina.
2017;48:432-434.].
PMID- 28499057
TI - Adaptive Optics Scanning Laser Ophthalmoscopy and Multimodal Imaging of Peau
D'Orange in Pseudoxanthoma Elasticum.
AB - A 41-year-old male with pseudoxanthoma elasticum who presented with progressive
vision loss in his left periphery is discussed. Bilateral angioid streaks, optic
disc drusen, choroidal neovascularization, and peau d'orange were present.
Imaging of the area with peau d'orange with adaptive optics scanning laser
ophthalmoscopy and en face optical coherence tomography at Bruch's membrane (BM)
revealed a pattern identical to the patches of peau d'orange visible with
conventional fundus imaging techniques. These results show that structural
abnormalities at the level of BM, likely a result of calcification, correlate
with the characteristic "orange peel" pattern known as peau d'orange. [Ophthalmic
Surg Lasers Imaging Retina. 2017;48:436-440.].
PMID- 28499058
TI - Association of Myelinated Retinal Nerve Fibers With Acquired Mulberry Retinal
Astrocytoma: Coincidental or Relational?
AB - Retinal astrocytoma is an important ocular finding for diagnosis of tuberous
sclerosis complex and is also an association of neurofibromatosis. The authors
present findings of a case of acquired astrocytoma associated with myelinated
retinal nerve fibers. The authors also discuss the images and possible cause
effect relationship between them. [Ophthalmic Surg Lasers Imaging Retina.
2017;48:441-442.].
PMID- 28499059
TI - 8 Questions with Darius Moshfeghi.
PMID- 28499060
TI - Follow-up of tinea capitis with trichoscopy: a prospective clinical study.
PMID- 28499061
TI - Primary skin manifestation of plasmoblastic lymphoma in an AIDS patient with long
term survival.
PMID- 28499062
TI - Compound annotation in liquid chromatography/high-resolution mass spectrometry
based metabolomics: robust adduct ion determination as a prerequisite to
structure prediction in electrospray ionization mass spectra.
AB - RATIONALE: A bottleneck in metabolic profiling of complex biological extracts is
confident, non-supervised annotation of ideally all contained, chemically highly
diverse small molecules. Recent computational strategies combining sum formula
prediction with in silico fragmentation achieve confident de novo annotation,
once the correct neutral mass of a compound is known. Current software solutions
for automated adduct ion assignment, however, are either publicly unavailable or
have been validated against only few experimental electrospray ionization (ESI)
mass spectra. METHODS: We here present findMAIN (find Main Adduct IoN), a new
heuristic approach for interpreting ESI mass spectra. findMAIN scores MS1 spectra
based on explained intensity, mass accuracy and isotope charge agreement of
adducts and related ionization products and annotates peaks of the (de)protonated
molecule and adduct ions. The approach was validated against 1141 ESI positive
mode spectra of chemically diverse standard compounds acquired on different high
resolution mass spectrometric instruments (Orbitrap and time-of-flight).
Robustness against impure spectra was evaluated. RESULTS: Correct adduct ion
assignment was achieved for up to 83% of the spectra. Performance was independent
of compound class and mass spectrometric platform. The algorithm proved highly
tolerant against spectral contamination as demonstrated exemplarily for co
eluting compounds as well as systematically by pairwise mixing of spectra. When
used in conjunction with MS-FINDER, a state-of-the-art sum formula tool, correct
sum formulas were obtained for 77% of spectra. It outperformed both 'brute force'
approaches and current state-of-the-art annotation packages tested as potential
alternatives. Limitations of the heuristic pertained to poorly ionizing compounds
and cationic compounds forming [M]+ ions. CONCLUSIONS: A new, validated approach
for interpreting ESI mass spectra is presented, filling a gap in the nontargeted
metabolomics workflow. It is freely available in the latest version of R package
InterpretMSSpectrum.
PMID- 28499064
TI - Enhancing auxin accumulation in maize root tips improves root growth and dwarfs
plant height.
AB - Maize is a globally important food, feed crop and raw material for the food and
energy industry. Plant architecture optimization plays important roles in maize
yield improvement. PIN-FORMED (PIN) proteins are important for regulating auxin
spatiotemporal asymmetric distribution in multiple plant developmental processes.
In this study, ZmPIN1a overexpression in maize increased the number of lateral
roots and inhibited their elongation, forming a developed root system with longer
seminal roots and denser lateral roots. ZmPIN1a overexpression reduced plant
height, internode length and ear height. This modification of the maize phenotype
increased the yield under high-density cultivation conditions, and the developed
root system improved plant resistance to drought, lodging and a low-phosphate
environment. IAA concentration, transport capacity determination and application
of external IAA indicated that ZmPIN1a overexpression led to increased IAA
transport from shoot to root. The increase in auxin in the root enabled the plant
to allocate more carbohydrates to the roots, enhanced the growth of the root and
improved plant resistance to environmental stress. These findings demonstrate
that maize plant architecture can be improved by root breeding to create an ideal
phenotype for further yield increases.
PMID- 28499065
TI - Not sick enough: Experiences of carers of people with mental illness negotiating
care for their relatives with mental health services.
AB - : WHAT IS KNOWN ON THE SUBJECT?: Existing literature provides insight into the
general experience of carers of people with a mental illness. Previous studies
have found that carers experience a range of emotions when looking after their
relatives with a mental illness. However, experiences of carers as they engage
with the healthcare system is largely absent from the literature. WHAT THIS PAPER
ADDS TO EXISTING KNOWLEDGE?: This paper identified the experiences of carers when
their relatives are experiencing a crisis or acutely unwell. Carers found
themselves in the middle between mental health services and their relatives.
Strategies employed by carers to ensure their relatives receive adequate care
were identified from this study. This paper identified how carers needed to
become more assertive in order to receive adequate care for their relatives, and
this finding has implications for any future carer education. WHAT ARE THE
IMPLICATIONS FOR PRACTICE?: The participants identified the need to work more
collaboratively with carers of people with a mental illness as they seek
treatment for their relatives in order to achieve better health outcomes for the
patients. Improved health service engagement of carers was seen by participants
to assist them to better care for their relative. The study also found that there
needs to be a clearer definition as to what constitutes mental health crisis and
how carers are able to intervene during this period. Services could provide clear
information concerning crisis services and in particular triage. ABSTRACT: Aim
The literature reporting experiences of relatives of people with mental illness
regarding their interactions with mental health services identifies many
commonalities. However, the actual experience of carers engaging the services and
understanding healthcare systems remains a gap in the literature. The aim of this
study was to explore the experiences of carers (of people with a severe mental
illness) in a major area mental health service in Victoria Australia as they
fulfil their caring role while negotiating support for their relative. A carer is
defined as a family member or significant other who is the primary individual who
provides informal care for a person with severe mental illness and may or may not
be in receipt of income supplement for such a role. Specifically this study has a
focus on the experience of the carer when negotiating care needs or admission
with a mental health service. Method A qualitative descriptive approach was used
with five focus groups as a means of data collection. Ethical approval for the
study was obtained from both the hospital and universities ethics committees.
Results Key themes identified using thematic analysis are presented in the words
of the carers and include: "Juggling" between services; We became assertive and
If only they would listen. Often carers were advocating for their relative and
needing to negotiate between services (police and crisis assessment teams) to
gain any form of assessment or intervention. Carers often spent a great deal of
time on the phone to services only to be told that their relative was "not sick
enough" to access care or that no response would occur without another service
also being involved. Discussion Our research highlights the importance of working
collaboratively with informal carers and acknowledging their valuable
contribution to the care of their relatives with a severe mental illness. It is
very important that adequate support is given to carers especially during the
period when their relatives are experiencing a crisis. An understanding of their
experiences ensures a more family focused approach towards care. The study
findings should enable the healthcare team to focus attention on the issues which
are most pertinent to carers. Nurses are advocates not only for the patient but
also for their families. Relevance statement Carers supporting a person who
experiences mental illness can often find themselves in difficult and emotionally
challenging situations such as at times of crisis and admission to mental health
services. The fourth and latest Australian National Mental Health Plan (2009
2014) acknowledged these concerns and highlighted the need to recognize the role
of carers in promoting well-being and recovery of the relative with a mental
illness. The plan acknowledges that families are often best placed to recognize
signs of relapse in their family members with a mental illness and discharge
planning should include the involvement of family members (Commonwealth of
Australia, ). To achieve best care outcomes for consumers, mental health nurses
need to recognize the role of the carer and collaborate in care planning.
PMID- 28499063
TI - High efficient multisites genome editing in allotetraploid cotton (Gossypium
hirsutum) using CRISPR/Cas9 system.
AB - Gossypium hirsutum is an allotetraploid with a complex genome. Most genes have
multiple copies that belong to At and Dt subgenomes. Sequence similarity is also
very high between gene homologues. To efficiently achieve site/gene-specific
mutation is quite needed. Due to its high efficiency and robustness, the CRISPR
(clustered regularly interspaced short palindromic repeats)/Cas9 system has
exerted broad site-specific genome editing from prokaryotes to eukaryotes. In
this study, we utilized a CRISPR/Cas9 system to generate two sgRNAs in a single
vector to conduct multiple sites genome editing in allotetraploid cotton. An
exogenously transformed gene Discosoma red fluorescent protein2(DsRed2) and an
endogenous gene GhCLA1 were chosen as targets. The DsRed2-edited plants in T0
generation reverted its traits to wild type, with vanished red fluorescence the
whole plants. Besides, the mutated phenotype and genotype were inherited to their
T1 progenies. For the endogenous gene GhCLA1, 75% of regenerated plants exhibited
albino phenotype with obvious nucleotides and DNA fragments deletion. The
efficiency of gene editing at each target site is 66.7-100%. The mutation
genotype was checked for both genes with Sanger sequencing. Barcode-based high
throughput sequencing, which could be highly efficient for genotyping to a
population of mutants, was conducted in GhCLA1-edited T0 plants and it matched
well with Sanger sequencing results. No off-target editing was detected at the
potential off-target sites. These results prove that the CRISPR/Cas9 system is
highly efficient and reliable for allotetraploid cotton genome editing.
PMID- 28499066
TI - Perceiving social pressure not to feel negative predicts depressive symptoms in
daily life.
AB - BACKGROUND: Western societies often overemphasize the pursuit of happiness, and
regard negative feelings such as sadness or anxiety as maladaptive and unwanted.
Despite this emphasis on happiness, the amount of people suffering from
depressive complaints is remarkably high. To explain this apparent paradox, we
examined whether experiencing social pressure not to feel sad or anxious could in
fact contribute to depressive symptoms. METHODS: A sample of individuals (n =
112) with elevated depression scores (Patient Health Questionnaire [PHQ-9] >= 10)
took part in an online daily diary study in which they rated their depressive
symptoms and perceived social pressure not to feel depressed or anxious for 30
consecutive days. Using multilevel VAR models, we investigated the temporal
relation between this perceived social pressure and depressive symptoms to
determine directionality. RESULTS: Primary analyses consistently indicated that
experiencing social pressure predicts increases in both overall severity scores
and most individual symptoms of depression, but not vice versa. A set of
secondary analyses, in which we adopted a network perspective on depression,
confirmed these findings. Using this approach, centrality analysis revealed that
perceived social pressure not to feel negative plays an instigating role in
depression, reflected by the high out- and low instrength centrality of this
pressure in the various depression networks. CONCLUSIONS: Together, these
findings indicate how perceived societal norms may contribute to depression,
hinting at a possible malignant consequence of society's denouncement of negative
emotions. Clinical implications are discussed.
PMID- 28499067
TI - Nitrogen and Fluorine-Codoped Carbon Nanowire Aerogels as Metal-Free
Electrocatalysts for Oxygen Reduction Reaction.
AB - The development of active, durable, and low-cost catalysts to replace noble metal
based materials is highly desirable to promote the sluggish oxygen reduction
reaction in fuel cells. Herein, nitrogen and fluorine-codoped three-dimensional
carbon nanowire aerogels, composed of interconnected carbon nanowires, were
synthesized for the first time by a hydrothermal carbonization process. Owing to
their porous nanostructures and heteroatom-doping, the as-prepared carbon
nanowire aerogels, with optimized composition, present excellent electrocatalytic
activity that is comparable to commercial Pt/C. Remarkably, the aerogels also
exhibit superior stability and methanol tolerance. This synthesis procedure paves
a new way to design novel heteroatom-doped catalysts.
PMID- 28499068
TI - MutMapPlus identified novel mutant alleles of a rice starch branching enzyme IIb
gene for fine-tuning of cooked rice texture.
AB - Physicochemical properties of storage starch largely determine rice grain quality
and food characteristics. Therefore, modification of starch property is effective
to fine-tune cooked rice textures. To obtain new resources with modified starch
property as breeding materials, we screened a mutant population of a japonica
cultivar Nipponbare and found two independent mutant lines, altered
gelatinization (age)1 and age2, with moderate changes in starch gelatinization
property. A combination of conventional genetic analyses and the latest mapping
method, MutMapPlus, revealed that both of these lines harbour novel independent
mutant alleles of starch branching enzyme IIb (BEIIb) gene. In age1, amino acid
substitution of Met-723 to Lys completely abolished BEIIb enzyme activity without
significant reduction in its protein level. A transposon insertion in an intron
of BEIIb gene reduced BEIIb protein level and activity in age2. Production of a
series of the mutant lines by combining age alleles and indica-type starch
synthase IIa allele established stepwise alteration of the physicochemical
properties of starch including apparent amylose content, thermal property,
digestibility by alpha-amylase and branched structures of amylopectin. Consistent
with the alteration of starch properties, the results of a sensory evaluation
test demonstrated that warm cooked rice of the mutants showed a variety of
textures without marked reduction in overall palatability. These results suggest
that a series of the mutant lines are capable of manipulation of cooked rice
textures.
PMID- 28499070
TI - Higher risk of hepatocellular carcinoma in chronic hepatitis B vs chronic
hepatitis C after achievement of virologic response.
AB - It is unclear whether the achievement of virologic response modifies the risk of
hepatocellular carcinoma (HCC) differently in chronic hepatitis B (CHB) and
chronic hepatitis C (CHC). Our aim was to compare the risk of HCC between
patients with CHB and CHC who achieved virological response. We analysed data
from patients with CHB treated with entecavir (n=2000) or CHC treated with peg
interferon and ribavirin (n=733) at a tertiary hospital from 2004 to 2011.
Virological response was defined as serum HBV DNA<15 IU/mL at 1 year of treatment
for CHB or the achievement of sustained virologic response for CHC. Virological
response was achieved in 1520 patients with CHB (76.0%) and 475 patients with CHC
(64.8%). During the median follow-up period of 6 years, 228 patients with CHB
(11.4%) and 59 patients with CHC (8.0%) developed HCC. Among patients with
virological response, CHB was independently associated with a significantly
higher incidence of HCC (hazard ratio, 2.17; 95% CI, 1.30-3.63; P=.003) than CHC.
Among patients without virological response, there were no differences in HCC
incidence between the two cohorts (P=.52). In patients with cirrhosis at
baseline, the incidence of HCC did not differ between the two cohorts even after
achieving virological response (P>.99). In conclusion, patients with CHB treated
with entecavir were associated with a higher risk of HCC compared to patients
with CHC treated with peg-interferon and ribavirin after achieving virological
response. However, the risk of HCC did not differ between the two cohorts if the
patients had cirrhosis at baseline, even if virological response was achieved.
PMID- 28499069
TI - The association of hormone signalling genes, transcription and changes in shoot
anatomy during moso bamboo growth.
AB - Moso bamboo is a large, woody bamboo with the highest ecological, economic and
cultural value of all the bamboo types and accounts for up to 70% of the total
area of bamboo grown. However, the spatiotemporal variation role of moso bamboo
shoot during growth period is still unclear. We found that the bamboo shoot
growth can be divided into three distinct periods, including winter growth, early
growth and late growth based on gene expression and anatomy. In the early growth
period, lateral buds germinated from the top of the bamboo joint in the shoot
tip. Intercalary meristems grew vigorously during the winter growth period and
early growth period, but in the late growth period, mitosis in the intercalary
meristems decreased. The expression of cell cycle-associated genes and the
quantity of differentially expressed genes were higher in early growth than those
in late growth, appearing to be influenced by hormonal concentrations. Gene
expression analysis indicates that hormone signalling genes play key roles in
shoot growth, while auxin signalling genes play a central role. In situ
hybridization analyses illustrate how auxin signalling genes regulate apical
dominance, meristem maintenance and lateral bud development. Our study provides a
vivid picture of the dynamic changes in anatomy and gene expression during shoot
growth in moso bamboo, and how hormone signalling-associated genes participate in
moso bamboo shoot growth.
PMID- 28499071
TI - Natural Abundance 17 O DNP NMR Provides Precise O-H Distances and Insights into
the Bronsted Acidity of Heterogeneous Catalysts.
AB - Heterogeneous Bronsted acid catalysts are tremendously important in industry,
particularly in catalytic cracking processes. Here we show that these Bronsted
acid sites can be directly observed at natural abundance by 17 O DNP surface
enhanced NMR spectroscopy (SENS). We additionally show that the O-H bond length
in these catalysts can be measured with sub-picometer precision, to enable a
direct structural gauge of the lability of protons in a given material, which is
correlated with the pH of the zero point of charge of the material. Experiments
performed on materials impregnated with pyridine also allow for the direct
detection of intermolecular hydrogen bonding interactions through the lengthening
of O-H bonds.
PMID- 28499072
TI - Sequencing of bulks of segregants allows dissection of genetic control of amylose
content in rice.
AB - Amylose content (AC) is a key quality trait in rice. A cross between Oryza
glaberrima (African rice) and Oryza sativa (Asian rice) segregating for AC was
analysed by sequencing bulks of individuals with high and low AC. SNP associated
with the granule bound starch synthase (GBSS1) locus on chromosome 6 were
polymorphic between the bulks. In particular, a G/A SNP that would result in an
Asp to Asn mutation was identified. This amino acid substitution may be
responsible for differences in GBSS activity as it is adjacent to a disulphide
linkage conserved in all grass GBSS proteins. Other polymorphisms in genomic
regions closely surrounding this variation may be the result of linkage drag. In
addition to the variant in the starch biosynthesis gene, SNP on chromosomes 1 and
11 linked to AC was also identified. SNP was found in the genes encoding the NAC
and CCAAT-HAP5 transcription factors that have previously been linked to starch
biosynthesis. This study has demonstrated that the approach of sequencing bulks
was able to identify genes on different chromosomes associated with this complex
trait.
PMID- 28499073
TI - Arabidopsis ZED1-related kinases mediate the temperature-sensitive intersection
of immune response and growth homeostasis.
AB - Activation of the immune response in plants antagonizes growth and development in
the absence of pathogens, and such an autoimmune phenotype is often suppressed by
the elevation of ambient temperature. However, molecular regulation of the
ambient temperature-sensitive intersection of immune response and growth is
largely elusive. A genetic screen identified an Arabidopsis mutant, zed1-D, by
its high temperature-dependent growth retardation. A combination of molecular,
cytological and genetic approaches was used to investigate the molecular basis
behind the temperature-sensitive growth and immune response in zed1-D. A dominant
mutation in HOPZ-ETI-DEFICIENT 1 (ZED1) is responsible for a high temperature
dependent autoimmunity and growth retardation in zed1-D. The autoimmune phenotype
in zed1-D is dependent on the HOPZ-ACTIVATED RESISTANCE 1 (ZAR1). ZED1 and some
ZED1-related kinases (ZRKs) are induced by elevated temperature and function
cooperatively to suppress the immune response by modulating the transcription of
SUPPRESSOR OF NPR1-1 CONSTITUTIVE 1 (SNC1) in the absence of pathogens. Our data
reveal a previously unidentified role of ZRKs in the ambient temperature
sensitive immune response in the absence of pathogens, and thus reveals a
possible molecular mechanism underlying the temperature-mediated intersection of
immune response and growth in plants.
PMID- 28499074
TI - Drug development and registration: Challenges and opportunities in ovarian
cancer.
PMID- 28499075
TI - Regulatory considerations on endpoints in ovarian cancer drug development.
AB - Ovarian cancer remains a disease entity that is responsible for considerable
morbidity and mortality among women worldwide. Modern drug research pipelines and
accelerated drug development timelines applied to other disease entities have
begun to make an impact on treatment options for patients with advanced ovarian
cancer, as exemplified by the recent accelerated approval of 2 agents for this
disease as the forerunners of a growing number of registrational trials.
Regulatory flexibility for this serious and life-threatening condition spurs the
consideration of intermediate endpoints for regulatory trial design, including
potential applications in the development of newer therapeutic classes such as
targeted therapies and immunotherapies for patients with advanced ovarian cancer.
Cancer 2017;123:2604-8. (c) 2017 American Cancer Society.
PMID- 28499077
TI - Unconventional Behavior of Friction at the Nanoscale beyond Amontons' Law.
AB - By means of a many-body van der Waals (vdW)-corrected density functional theory
approach, the atomic-scale friction of a prototypical tip-substrate system
consisting of an Si tip and a graphene substrate is studied. In a loading-sliding
process, the tip-substrate distance is found to be essential for nanofrictional
behavior, through determining the competition between vdW contributions and
electronic contributions. As the tip approaches the substrate, this competition
results in a smooth transition of normal forces from attraction to repulsion, and
the friction coefficient in turn undergoes a sign change from negative to
positive with possible giant magnitude and strong anisotropy. The loading-sliding
process does not introduce any chemical modification of the underlying system.
These findings reveal the boundary of validity of Amontons' law, unify negative
and giant friction coefficients, rationalize the experimentally observed
anisotropy of nanofriction, and are universal when vdW interactions are crucial,
all of which are helpful to establish a comprehensive picture of nanofriction.
PMID- 28499076
TI - Single Cell Analysis Linking Ribosomal (r)DNA and rRNA Copy Numbers to Cell Size
and Growth Rate Provides Insights into Molecular Protistan Ecology.
AB - Ribosomal (r)RNA and rDNA have been golden molecular markers in microbial
ecology. However, it remains poorly understood how ribotype copy number (CN)
based characteristics are linked with diversity, abundance, and activity of
protist populations and communities observed at organismal levels. Here, we
applied a single-cell approach to quantify ribotype CNs in two ciliate species
reared at different temperatures. We found that in actively growing cells, the
per-cell rDNA and rRNA CNs scaled with cell volume (CV) to 0.44 and 0.58 powers,
respectively. The modeled rDNA and rRNA concentrations thus appear to be much
higher in smaller than in larger cells. The observed rRNA:rDNA ratio scaled with
CV0.14 . The maximum growth rate could be well predicted by a combination of per
cell ribotype CN and temperature. Our empirical data and modeling on single-cell
ribotype scaling are in agreement with both the metabolic theory of ecology and
the growth rate hypothesis, providing a quantitative framework for linking
cellular rDNA and rRNA CNs with body size, growth (activity), and biomass
stoichiometry. This study also demonstrates that the expression rate of rRNA
genes is constrained by cell size, and favors biomass rather than abundance-based
interpretation of quantitative ribotype data in population and community ecology
of protists.
PMID- 28499078
TI - Genomewide analysis of the lateral organ boundaries domain gene family in
Eucalyptus grandis reveals members that differentially impact secondary growth.
AB - Lateral Organ Boundaries Domain (LBD) proteins are plant-specific transcription
factors playing crucial roles in growth and development. However, the function of
LBD proteins in Eucalyptus grandis remains largely unexplored. In this study, LBD
genes in E. grandis were identified and characterized using bioinformatics
approaches. Gene expression patterns in various tissues and the transcriptional
responses of EgLBDs to exogenous hormones were determined by qRT-PCR. Functions
of the selected EgLBDs were studied by ectopically overexpressing in a hybrid
poplar (Populus alba * Populus glandulosa). Expression levels of genes in the
transgenic plants were investigated by RNA-seq. Our results showed that there
were forty-six EgLBD members in the E. grandis genome and three EgLBDs displayed
xylem- (EgLBD29) or phloem-preferential expression (EgLBD22 and EgLBD37).
Confocal microscopy indicated that EgLBD22, EgLBD29 and EgLBD37 were localized to
the nucleus. Furthermore, we found that EgLBD22, EgLBD29 and EgLBD37 were
responsive to the treatments of indol-3-acetic acid and gibberellic acid. More
importantly, we demonstrated EgLBDs exerted different influences on secondary
growth. Namely, 35S::EgLBD37 led to significantly increased secondary xylem,
35S::EgLBD29 led to greatly increased phloem fibre production, and 35S::EgLBD22
showed no obvious effects. We revealed that key genes related to gibberellin,
ethylene and auxin signalling pathway as well as cell expansion were
significantly up- or down-regulated in transgenic plants. Our new findings
suggest that LBD genes in E. grandis play important roles in secondary growth.
This provides new mechanisms to increase wood or fibre production.
PMID- 28499080
TI - Efficient Electrocatalytic Reduction of CO2 by Nitrogen-Doped Nanoporous
Carbon/Carbon Nanotube Membranes: A Step Towards the Electrochemical CO2
Refinery.
AB - Herein we introduce a straightforward, low cost, scalable, and technologically
relevant method to manufacture an all-carbon, electroactive, nitrogen-doped
nanoporous-carbon/carbon-nanotube composite membrane, dubbed "HNCM/CNT". The
membrane is demonstrated to function as a binder-free, high-performance gas
diffusion electrode for the electrocatalytic reduction of CO2 to formate. The
Faradaic efficiency (FE) for the production of formate is 81 %. Furthermore, the
robust structural and electrochemical properties of the membrane endow it with
excellent long-term stability.
PMID- 28499079
TI - Development of an atrophic acne scar risk assessment tool.
AB - BACKGROUND: Acne is a chronic dermatological disease predominantly afflicting
young adults and is often associated with the development of scars. Acne scarring
is usually avoidable when acne is managed early and effectively. However, acne
patients often fail to seek early treatment. New and innovative tools to raise
awareness are needed. OBJECTIVE: This study presents the development and
assessment of a tool aiming to assess the risk of atrophic acne scars. METHODS: A
systematic literature review of clinical risk factors for acne scars, a Delphi
like survey of dermatological experts in acne and secondary data analysis, were
conducted to produce an evidence-based risk assessment tool. The tool was
assessed both with a sample of young adults with and without scars and was
assessed via a database cross-validation. RESULTS: A self-administered tool for
risk assessment of developing atrophic acne scars in young adults was developed.
It is a readily comprehensible and practical tool for population education and
for use in medical practices. It comprises of four risk factors: worst ever
severity of acne, duration of acne, family history of atrophic acne scars and
lesion manipulation behaviours. It provides a dichotomous outcome: lower vs.
higher risk of developing scars, thereby categorizing nearly two-thirds of the
population correctly, with sensitivity of 82% and specificity of 43%. CONCLUSION:
The present tool was developed as a response to current challenges in acne scar
prevention. A potential benefit is to encourage those at risk to self-identify
and to seek active intervention of their acne. In clinical practice, we expect
this tool may help clinicians identify patients at risk of atrophic acne scarring
and underscore their requirement for rapid and effective acne treatment.
PMID- 28499081
TI - Negative correlation between serum uric acid and kidney URAT1 mRNA expression
caused by resveratrol in rats.
AB - SCOPE: This study established a hyperuricemic rat model to elucidate the effect
of resveratrol on the transport of UA in the kidney. METHODS AND RESULTS:
Hyperuricemia was induced in rats through daily oral gavage of a potassium
oxonate and UA mixture over 3 weeks. Our results revealed that resveratrol
significantly reduced the serum UA levels but not creatinine, c-creative protein,
alanine aminotransferase, or aspartate aminotransferase levels in these rats.
Furthermore, renal URAT1 and OAT1 mRNA expression were significantly higher in
the rats treated with allopurinol than in those with no treatment. Therefore,
allopurinol not only inhibited UA production but also mediated renal URAT1 and
OAT1 expression. The correlation analysis revealed that UA levels correlated
negatively with renal IL-6 mRNA expression in rats treated with allopurinol.
Moreover, URAT1 showed strong immunoreactivity in the distal convoluted tubule of
rats treated with allopurinol or resveratrol and in hyperuricemic treated with
allopurinol. Finally, in the rats treated with resveratrol, UA levels correlated
negatively with renal URAT1 mRNA expression; thus, resveratrol reduced URAT1 mRNA
expression under high UA levels, thereby reducing UA reabsorption in renal cells.
CONCLUSION: Resveratrol contributes to URAT1 expression, which is potentially
useful in therapeutic strategies aimed at treating hyperuricemia.
PMID- 28499083
TI - Brief Psychotic Episode Caused by Advair Diskus in a Pediatric Patient.
PMID- 28499082
TI - Exacerbation of liver steatosis following exposure to famine and overnutrition.
AB - SCOPE: People suffering from famine in early life and overnutrition in adulthood
may have an increased risk for liver steatosis. We aimed to investigate the
effects and mechanisms of early nutrition restriction and overnutrition on de
novo lipogenesis in the liver. METHODS AND RESULTS: Three-wk-old male rats were
food restricted for 4 wk and refed a high-fat or normal fat diet individually in
metabolic cages for 9 wk. Weight-matched groups were also set up. Fatty acid
synthetase expression was measured to estimate de novo lipogenesis in the liver.
Parameters of glucose and lipid metabolism were measured with isotope assays. All
four groups had comparable body weights. However, the famine high-fat diet group
had the highest degree of liver steatosis, the greatest body fat ratio, and
insulin resistance. Lipid accumulation, fatty acid synthetase expression, and
gluconeogenesis in the liver were significantly higher in the famine and high-fat
diet groups (p < 0.05). Moreover, these groups also had markedly lower muscle
glucose uptake. CONCLUSION: Under famine and high-fat refeeding stress, rats were
extremely susceptible to developing hepatic steatosis. This is presumably a
consequence of upregulation of de novo lipogenesis and enhanced glucose flux from
muscle to de novo lipogenesis in the liver.
PMID- 28499084
TI - Psychological Assessment of Emirati Patients Pursuing Bariatric Surgery for
Obesity.
AB - Background: Obesity is currently a rapidly growing global problem of epidemic
proportions and is especially prevalent in economically developed countries such
as the United Arab Emirates. Obese individuals are increasingly considering
bariatric surgery as their preferred means of choice for the reduction of excess
body fat. This study explored the psychological characteristics that may
potentially complicate the surgical management of obesity. Methods: This was a
cross-sectional study of Emirati patients attending a bariatric clinic at Tawam
Hospital, Al Ain, United Arab Emirates, between December 2010 and February 2012.
Participants were assessed using standard clinical psychiatric interviews. Also
used were screening instruments such as the Hospital Anxiety and Depression
Scale, Sheehan Disability Scale (SDS), Body Image Quality of Life Inventory
(BIQLI), and Multidimensional Body-Self Relations Questionnaire-Appearance Scale
(MBSRQ-AS). Results: A total of 105 patients, 70% of whom were female,
participated in this study. Participants were found to have frequencies of
anxiety and depressive symptoms at levels of 24% and 13%, respectively.
Participants also reported perceived functional disabilities in the following:
work/school (27%), social life (36%), family/home (35%), and religious duties
(39%). A total of 13 participants (12%) had BIQLI scores showing slight-to
moderate effects on their quality of life. The mean MBSRQ-AS subscale on self
classified weight was higher than the reported norms. Anxiety and depressive
symptoms positively correlated with functional impairment (SDS) and negatively
correlated with quality of life (BIQLI) (P = .000). MBSRQ-AS subscales
significantly correlated with depression, functional impairment, and quality of
life (P <= .035). Conclusions: Anxiety, depression, perceived functional
disability, impairment in quality of life, and disturbance of self-image were
found to be common among participants in the study pursuing bariatric surgery for
obesity. Recognition, assessment, and treatment of these symptoms are expected to
be conducive to positive outcomes of bariatric surgery.
PMID- 28499085
TI - Simultaneous Oxidation and Sequestration of As(III) from Water by Using Redox
Polymer-Based Fe(III) Oxide Nanocomposite.
AB - Water decontamination from As(III) is an urgent but still challenging task.
Herein, we fabricated a bifunctional nanocomposite HFO@PS-Cl for highly efficient
removal of As(III), with active chlorine covalently binding spherical polystyrene
host for in situ oxidation of As(III) to As(V), and Fe(III) hydroxide (HFO)
nanoparticles (NPs) embedded inside for specific As(V) removal. HFO@PS-Cl could
work effectively in a wide pH range (5-9), and other substances like sulfate,
chloride, bicarbonate, silicate, and humic acid exert insignificant effect on
As(III) removal. As(III) sequestration is realized via two pathways, that is,
oxidation to As(V) by the active chlorine followed by specific As(V) adsorption
onto HFO NPs, and As(III) adsorption onto HFO NPs followed by oxidation to As(V).
The exhausted HFO@PS-Cl could be refreshed for cyclic runs with insignificant
capacity loss by the combined regeneration strategy, that is, alkaline solution
to rinse the adsorbed As(V) and NaClO solution to renew the host oxidation
capability. In addition, fixed-bed experiments demonstrated that the HFO@PS-Cl
column could generate >1760 bed volume (BV) effluent from a synthetic As(III)
containing groundwater to meet the drinking water standard (<10 MUg As/L),
whereas other two HFO nanocomposites, HFO@PS-N and HFO@D201 could only generate
450 and 600 BV effluents under otherwise identical conditions.
PMID- 28499086
TI - Rapid Diagnostic Assay for Intact Influenza Virus Using a High Affinity
Hemagglutinin Binding Protein.
AB - Influenza is a ubiquitous and recurring infection that results in approximately
500 000 deaths globally each year. Commercially available rapid diagnostic tests
are based upon detection of the influenza nucleoprotein, which are limited in
that they are unable to differentiate by species and require an additional viral
lysis step. Sample preprocessing can be minimized or eliminated by targeting the
intact influenza virus, thereby reducing assay complexity and leveraging the
large number of hemagglutinin proteins on the surface of each virus. Here, we
report the development of a paper-based influenza assay that targets the
hemagglutinin protein; the assay employs a combination of antibodies and novel
computationally designed, recombinant affinity proteins as the capture and
detection agents. This system leverages the customizability of recombinant
protein design to target the conserved receptor-binding pocket of the
hemagglutinin protein and to match the trimeric nature of hemagglutinin for
improved avidity. Using this assay, we demonstrate the first instance of intact
influenza virus detection using a combination of antibody and affinity proteins
within a porous network. The recombinant head region binder based assays yield
superior analytical sensitivity as compared to the antibody based assay, with
lower limits of detection of 3.54 * 107 and 1.34 * 107 CEID50/mL for the mixed
and all binder stacks, respectively. Not only does this work describe the
development of a novel influenza assay, it also demonstrates the power of
recombinant affinity proteins for use in rapid diagnostic assays.
PMID- 28499088
TI - Lewis Acid-Catalyzed Nucleophilic Addition of Indoles to in Situ-Generated 2
Amidoallyl Cations.
AB - We report herein the first Lewis acid-catalyzed generation of 2-amidoallyl
cations through ring-opening of 4-benzylidene-2-oxazolines with Sc(OTf)3. Upon
nucleophilic addition of indoles, indolylenamides were obtained with yields of 60
99% and excellent (Z)-selectivity. In addition, the novel strategy was also
successfully applied to pyrroles and naphthols as pi-nucleophiles. A Bronsted
acid-catalyzed process using TfOH formed in situ was ruled out by control
experiments.
PMID- 28499087
TI - Identification of Intrahelical Bifurcated H-Bonds as a New Type of Gate in K+
Channels.
AB - Gating of ion channels is based on structural transitions between open and closed
states. To uncover the chemical basis of individual gates, we performed a
comparative experimental and computational analysis between two K+ channels, KcvS
and KcvNTS. These small viral encoded K+ channel proteins, with a monomer size of
only 82 amino acids, resemble the pore module of all complex K+ channels in terms
of structure and function. Even though both proteins share about 90% amino acid
sequence identity, they exhibit different open probabilities with ca. 90% in
KcvNTS and 40% in KcvS. Single channel analysis, mutational studies and molecular
dynamics simulations show that the difference in open probability is caused by
one long closed state in KcvS. This state is structurally created in the
tetrameric channel by a transient, Ser mediated, intrahelical hydrogen bond. The
resulting kink in the inner transmembrane domain swings the aromatic rings from
downstream Phes in the cavity of the channel, which blocks ion flux. The frequent
occurrence of Ser or Thr based helical kinks in membrane proteins suggests that a
similar mechanism could also occur in the gating of other ion channels.
PMID- 28499089
TI - Nanoencapsulation of Aloe vera in Synthetic and Naturally Occurring Polymers by
Electrohydrodynamic Processing of Interest in Food Technology and Bioactive
Packaging.
AB - This work originally reports on the use of electrohydrodynamic processing (EHDP)
to encapsulate Aloe vera (AV, Aloe barbadensis Miller) using both synthetic
polymers, i.e., polyvinylpyrrolidone (PVP) and poly(vinyl alcohol) (PVOH), and
naturally occurring polymers, i.e., barley starch (BS), whey protein concentrate
(WPC), and maltodextrin. The AV leaf juice was used as the water-based solvent
for EHDP, and the resultant biopolymer solution properties were evaluated to
determine their effect on the process. Morphological analysis revealed that, at
the optimal processing conditions, synthetic polymers mainly produced fiber-like
structures, while naturally occurring polymers generated capsules. Average sizes
ranged from 100 nm to above 3 MUm. As a result of their different and optimal
morphology and, hence, higher AV content, PVP, in the form of nanofibers, and
WPC, of nanocapsules, were further selected to study the AV stability against
ultraviolet (UV) light exposure. Fourier transform infrared (FTIR) spectroscopy
confirmed the successful encapsulation of AV in the biopolymer matrices,
presenting both encapsulants a high chemical interaction with the bioactive
components. Ultraviolet-visible (UV-vis) spectroscopy showed that, while PVP
nanofibers offered a poor effect on the AV degradation during UV light exposure
(~10% of stability after 5 h), WPC nanobeads delivered excellent protection
(stability of >95% after 6 h). This was ascribed to positive interactions between
WPC and the hydrophilic components of AV and the inherent UV-blocking and oxygen
barrier properties provided by the protein. Therefore, electrospraying of food
hydrocolloids interestingly appears as a novel potential nanotechnology tool
toward the formulation of more stable functional foods and nutraceuticals.
PMID- 28499090
TI - Two-Dimensional Cadmium Chloride Nanosheets in Cadmium Telluride Solar Cells.
AB - In this study we make use of a liquid nitrogen-based thermomechanical cleavage
technique and a surface analysis cluster tool to probe in detail the tin
oxide/emitter interface at the front of completed CdTe solar cells. We show that
this thermomechanical cleavage occurs within a few angstroms of the SnO2/emitter
interface. An unexpectedly high concentration of chlorine at this interface,
~20%, was determined from a calculation that assumed a uniform chlorine
distribution. Angle-resolved X-ray photoelectron spectroscopy was used to further
probe the structure of the chlorine-containing layer, revealing that both sides
of the cleave location are covered by one-third of a unit cell of pure CdCl2, a
thickness corresponding to about one Cl-Cd-Cl molecular layer. We interpret this
result in the context of CdCl2 being a true layered material similar to
transition-metal dichalcogenides. Exposing cleaved surfaces to water shows that
this Cl-Cd-Cl trilayer is soluble, raising questions pertinent to cell
reliability. Our work provides new and unanticipated details about the structure
and chemistry of front surface interfaces and should prove important to improving
materials, processes, and reliability of next-generation CdTe-based solar cells.
PMID- 28499091
TI - Dynamics of a Water Droplet over a Sessile Oil Droplet: Compound Droplets
Satisfying a Neumann Condition.
AB - We report the dynamics of compound droplets with a denser liquid (water) droplet
over a less dense sessile droplet (mineral oil) that satisfies the Neumann
condition. For a fixed size of an oil droplet, depending on the size of the water
droplet, either it attains the axisymmetric position or tends to migrate toward
the edge of the oil droplet. For a water droplet-to-oil droplet at volume ratio
Vw/Vo >= 0.05, stable axisymmetric configuration is achieved; for Vw/Vo < 0.05,
migration of water droplet is observed. The stability and migration of water
droplets of size above and below critical size, respectively, are explained using
the force balance at the three-phase contact line and film tension. The larger
and smaller droplets that initially attain the axisymmetric position or some
radial position, respectively, evaporate continuously and thus migrate toward the
edge of the oil droplet. The radial location and migration of the water droplets
of different initial sizes with respect to time are studied. Experiments with
water droplets on a flat oil-air interface did not show migration, which
signified the role of the curved oil-air interface for droplet migration.
Finally, coalescence of water droplets of size above the critical size at the
axisymmetric position is demonstrated. Our compound droplet studies could be
beneficial for applications involving droplet transport where contamination due
to direct contact and pinning of droplets on solid surfaces is of concern.
Migration and coalescence of water droplets on curved oil-air interfaces could
open new frontiers in chemical and biological applications including multiphase
processing and biological interaction of cells and atmospheric chemistry.
PMID- 28499092
TI - Determining the Conduction Band-Edge Potential of Solar-Cell-Relevant Nb2O5
Fabricated by Atomic Layer Deposition.
AB - Often key to boosting photovoltages in photoelectrochemical and related solar
energy-conversion devices is the preferential slowing of rates of charge
recombination-especially recombination at semiconductor/solution,
semiconductor/polymer, or semiconductor/perovskite interfaces. In devices
featuring TiO2 as the semiconducting component, a common approach to slowing
recombination is to install an ultrathin metal oxide barrier layer or trap
passivating layer atop the semiconductor, with the needed layer often being
formed via atomic layer deposition (ALD). A particularly promising barrier layer
material is Nb2O5. Its conduction-band-edge potential ECB is low enough that
charge injection from an adsorbed molecular, polymeric, or solid-state light
absorber and into the semiconductor can still occur, but high enough that charge
recombination is inhibited. While a few measurements of ECB have been reported
for conventionally synthesized, bulk Nb2O5, none have been described for ALD
fabricated versions. Here, we specifically determine the conduction-band-edge
energy of ALD-fabricated Nb2O5 relative to that of TiO2. We find that, while the
value for ALD-Nb2O5 is indeed higher than that for TiO2, the difference is less
than anticipated based on measurements of conventionally synthesized Nb2O5 and is
dependent on the thermal history of the material. The implications of the
findings for optimization of competing interfacial rate processes, and therefore
photovoltages, are briefly discussed.
PMID- 28499093
TI - The Segond Fracture Is an Avulsion of the Anterolateral Complex.
AB - BACKGROUND: The Segond fracture was classically described as an avulsion fracture
of the anterolateral capsule of the knee. Recently, some authors have attributed
its pathogenesis to the "anterolateral ligament" (ALL). Biomechanical studies
that have attempted to reproduce this fracture in vitro have reported conflicting
findings. PURPOSE: To determine the anatomic characteristics of the Segond
fracture on plain radiographs and magnetic resonance imaging (MRI), to compare
this location with the location of the ALL described in prior radiographic and
anatomic publications, and to determine the fracture's attachments to the soft
tissue anterolateral structures of the knee. STUDY DESIGN: Case series; Level of
evidence, 4. METHODS: A total of 36 anterior cruciate ligament-injured patients
with Segond fractures (33 male, 3 female; mean age, 23.2 +/- 8.4 years) were
enrolled. MRI scans were reviewed to determine the anatomic characteristics of
the Segond fracture, including the following: proximal-distal (PD) length,
anterior-posterior (AP) width, medial-lateral (ML) width, PD distance to the
lateral tibial plateau, AP distance to the Gerdy tubercle (GT), and AP distance
from the GT to the posterior aspect of the fibular head. The attachment of the
anterolateral structures to the Segond fragment was then categorized as the
iliotibial band (ITB) or anterolateral capsule. Interrater reliability of the
measurements was determined by calculating the Spearman rank correlation
coefficient. MEDLINE, Web of Science, and the Cochrane Library were searched from
inception to May 2016 for the following keywords: (1) "Segond fracture," (2)
"anterolateral ligament," (3) "knee avulsion," (4) "lateral tibia avulsion," and
(5) "tibial plateau avulsion." All studies describing the anatomic location of
the Segond fracture and the ALL were included in the systematic review. RESULTS:
On plain radiographs, the mean distance of the midpoint of the fracture to the
lateral tibial plateau was 4.6 +/- 2.2 mm. The avulsed fracture had a mean PD
length of 9.2 +/- 2.5 mm and a mean ML width of 2.4 +/- 1.4 mm. On MRI, the mean
distance of the proximal fracture to the tibial plateau was 3.4 +/- 1.6 mm. The
mean PD length was 8.7 +/- 2.2 mm, while the mean AP width was 11.1 +/- 2.2 mm.
The mean distance between the GT and the center of the fracture was 26.9 +/- 3.3
mm, while the mean distance between the GT and the posterior fibular head was
53.9 +/- 4.4 mm. The mean distance of the midpoint of the fracture to the tibial
plateau was 7.8 +/- 2.7 mm, while the center of the fracture was 49.9% of the
distance between the GT and the posterior aspect of the fibular head. Analysis of
soft tissue structures attached to the fragment revealed that the ITB attached in
34 of 36 patients and the capsule attached in 34 of 36 patients. One patient had
only the capsule attached, another had only the ITB attached, and the last showed
neither clearly attached. A literature review of 20 included studies revealed no
difference between the previously described Segond fracture location and the
tibial insertion of the ALL. CONCLUSION: The results of this study confirmed that
while the Segond fracture occurs at the location of the tibial insertion of the
ALL, as reported in the literature, MRI was unable to identify any distinct
ligamentous attachment. MRI analysis revealed that soft tissue attachments to the
Segond fracture were the posterior fibers of the ITB and the lateral capsule in
94% of patients.
PMID- 28499094
TI - The Epidemiology and Effect of Sliding Injuries in Major and Minor League
Baseball Players.
AB - BACKGROUND: Although sliding occurs frequently in professional baseball, little
is known about the epidemiology and effect of injuries that occur during sliding
in this population of elite athletes. PURPOSE: To describe the incidence and
characteristics of sliding injuries, determine their effect in terms of time out
of play, and identify common injury patterns that may represent appropriate
targets for injury prevention programs in the future. STUDY DESIGN: Descriptive
epidemiologic study. METHODS: All offensive sliding injuries occurring in Major
League Baseball (MLB) and Minor League Baseball (MLB) that resulted in time out
of play during a span of 5 seasons (2011-2015) were identified. In addition to
player demographics, data extracted included time out of play, location on field
where injury occurred, level of play, treatment (surgical vs nonsurgical),
direction of slide (head vs feet first), body region injured, and diagnosis.
Descriptive statistics were used to describe the distribution of these injuries,
and injury rates were calculated per slide. RESULTS: From 2011 to 2015, 1633
injuries occurred as a result of a slide. The total number of days missed per
season was 4263. Surgical intervention was required for 134 (8.2%) injuries, and
the mean days missed was 66.5 for players treated surgically and 12.3 days for
players treated nonoperatively ( P < .001). MLB players were more likely than
MiLB players to require surgical intervention (12.3% vs 7.5%, P = .019). Injuries
to the hands/fingers represented 25.3% of all injuries and 31.3% of those
requiring surgery. Although the majority of injuries occurred at second base
(57%), the per-slide injury rate was similar across all bases ( P = .991). The
estimated overall frequency of injury in MLB was once per every 336 slides, and
the rate of injury for head- and feet-first slides was 1 in 249 and 413 slides,
respectively ( P = .119). CONCLUSION: Injuries occurring while sliding in
professional baseball result in a significant amount of time out of play for
these elite athletes. Injuries occurring at second base and those occurring to
the hands and fingers were most prevalent and may be an appropriate target for
future injury prevention programs.
PMID- 28499095
TI - TRPM7 Is Involved in Volume Regulation in Salivary Glands.
AB - Under hypotonic conditions, the regulatory volume decrease (RVD) is essential to
maintain physiological homeostasis and functions in diverse biological systems.
Intracellular Ca2+ has been reported as an important mediator of this response,
but the underlying Ca2+ mechanism responsible for RVD is still controversial.
Here we investigate the role of Ca2+ in the RVD response using live-cell imaging,
microspectrofluorimetry, and a patch-clamp technique. A typical RVD was observed
in submandibular gland acinar cells after swelling in a hypotonic solution,
whereas intracellular Ca2+ chelation completely inhibited the RVD response. The
incidence and magnitude of the Ca2+ transient were proportional to the degree of
hypotonicity of the extracellular medium, and there was a close relationship
between intracellular Ca2+ concentration and the volumetric changes of the cells.
Notably, this response was mediated by Ca2+-induced Ca2+ release, which is
triggered by Ca2+ influx via stretch-activated TRPM7 channels. Furthermore, we
detected the generation of Cl- currents in the swelling acinar cells upon
hypotonic stress, and the current profile matched that of the Ca2+-activated Cl-
currents. A specific inhibitor of Cl- currents also inhibited the RVD response.
In conclusion, an intracellular Ca2+ increase in response to osmotically induced
cell swelling plays a critical role in RVD in salivary gland acinar cells.
PMID- 28499096
TI - Genetic and phenotypic diversity of rhizobia nodulating chickpea (Cicer arietinum
L.) in soils from southern and central Ethiopia.
AB - Forty-two chickpea-nodulating rhizobia were isolated from soil samples collected
from diverse agro-ecological locations of Ethiopia and were characterized on the
basis of 76 phenotypic traits. Furthermore, 18 representative strains were
selected and characterized using multilocus sequence analyses of core and
symbiotic gene loci. Numerical analysis of the phenotypic characteristics grouped
the 42 strains into 4 distinct clusters. The analysis of the 16S rRNA gene of the
18 strains showed that they belong to the Mesorhizobium genus. On the basis of
the phylogenetic tree constructed from the combined genes sequences (recA, atpD,
glnII, and gyrB), the test strains were distributed into 4 genospecies
(designated as genospecies I-IV). Genospecies I, II, and III could be classified
with Mesorhizobium ciceri, Mesorhizobium abyssinicae, and Mesorhizobium shonense,
respectively, while genospecies IV might represent an unnamed Mesorhizobium
genospecies. Phylogenetic reconstruction based on the symbiosis-related (nifH and
nodA) genes supported a single cluster together with a previously described
symbiont of chickpea (M. ciceri and Mesorhizobium mediterraneum). Overall, our
results corroborate earlier findings that Ethiopian soils harbor phylogenetically
diverse Mesorhizobium species, justifying further explorative studies. The
observed differences in symbiotic effectiveness indicated the potential to select
effective strains for use as inoculants and to improve the productivity of
chickpea in the country.
PMID- 28499098
TI - Editor's Corner: Does a Little Drinking Make Your Heart Grow Stronger?
PMID- 28499097
TI - Substantivity of Carbodiimide Inhibition on Dentinal Enzyme Activity over Time.
AB - The use of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide HCl (EDC) has recently
been investigated for its effectiveness in the prevention of collagen degradation
over time and the improvement of resin-dentin bond durability. The objective of
the present study was to evaluate the effects of a 0.3 M EDC-containing
conditioner on endogenous enzymatic activities within the hybrid layer (HL)
created by a self-etch or an etch-and-rinse adhesive after 1 y. The activity
within the HL was examined using in situ zymography and confocal laser scanning
microscopy after 24 h or 1-y storage in artificial saliva. Dentin specimens were
bonded with Clearfil SE Bond (CSE) or XP Bond (XPB). For CSE, the self-etching
primer was applied and treated with 0.3 M EDC for 1 min, and then the bonding
agent was applied. For XPB, dentin was etched and treated with 0.3 M EDC for 1
min and then bonded with the primer-bonding agent. Control specimens were
prepared without EDC treatment. Slices containing the adhesive-dentin interface
were covered with fluorescein-conjugated gelatin and observed with a multiphoton
confocal microscope. Fluorescence intensity emitted by hydrolyzed fluorescein
conjugated gelatin was quantified, and the amount of gelatinolytic activity was
represented by the percentage of green fluorescence emitted within the HL. After
24 h of storage, enzymatic activity was detected by in situ zymography within the
HLs of both tested adhesives, with XPB higher than CSE ( P < 0.05). Almost no
fluorescence signal was detected when specimens were pretreated with EDC compared
to controls ( P < 0.05). After 1 y of storage, enzymatic activities significantly
increased for all groups (excluding XPB control) compared to 24-h storage ( P <
0.05), with EDC pretreated specimens exhibiting significantly lower activity than
controls ( P < 0.05). The present study showed, for the first time, that the use
of EDC for both the self-etch and the etch-and-rinse approaches results in the
reduction but not complete inhibition of matrix-bound collagenolytic enzyme
activities over time in the HL.
PMID- 28499099
TI - Evidence for Sex Convergence in Prevalence of Cannabis Use: A Systematic Review
and Meta-Regression.
AB - OBJECTIVE: Generally, cannabis use has been more prevalent in men than in women.
However, emerging evidence suggests that the prevalence of cannabis use is
converging among males and females from recent cohorts. This study aimed to
systematically summarize published literature on birth cohort changes in male-to
female ratios in prevalence of cannabis use. METHOD: Twenty-two studies with a
median sample size of 85,052 were identified for inclusion. Data were collected
between 1979 and 2010, representing birth cohorts from 1936 to 1999. For
quantitative synthesis, male-to-female ratios in prevalence of any cannabis use
were calculated for all 5-year birth cohorts available, generating 348 separate
ratios among birth cohorts from 1941 to 1995 in 30 countries. Random-effects meta
analyses generated pooled sex ratios, stratified by 5-year birth cohorts.
RESULTS: Of the 22 included studies, 10 reported some evidence of sex convergence
in cannabis use among more recent cohorts. Quantitative synthesis found that the
ratio of cannabis use prevalence in males and females decreased significantly
from 2.0 among cohorts born in 1941 to 1.3 among those born in 1995. CONCLUSIONS:
Findings support the narrowing sex gap in the prevalence of cannabis use. Results
are concordant with a broader literature demonstrating sex convergence in
prevalence of other substance use, particularly alcohol use and related harms.
Both young women and men should be the target of prevention and early
intervention efforts. Future research in more diverse global settings, especially
in low- and middle-income countries, would enhance the international scope of the
findings.
PMID- 28499101
TI - Targeting Stress Neuroadaptations for Addiction Treatment: A Commentary on Kaye
et al. (2017).
PMID- 28499102
TI - Alcohol Consumption and Mortality From Coronary Heart Disease: An Updated Meta
Analysis of Cohort Studies.
AB - OBJECTIVE: Previous meta-analyses estimate that low-volume alcohol consumption
protects against coronary heart disease (CHD). Potential errors in studies
include systematic misclassification of drinkers as abstainers, inadequate
measurement, and selection bias across the life course. METHOD: Prospective
studies of alcohol consumption and CHD mortality were identified in scholarly
databases and reference lists. Studies were coded for potential abstainer biases
and other study characteristics. The alcohol-CHD risk relationship was estimated
in mixed models with controls for potential biases. Stratified analyses were
performed based on variables identified as potential effect modifiers. RESULTS:
Fully adjusted meta-analysis of all 45 studies found significantly reduced CHD
mortality for current low-volume drinkers (relative risk [RR] = 0.80, 95% CI
[0.69, 0.93]) and all current drinkers (RR = 0.88, 95% CI [0.78, 0.99]). There
was evidence of effect modification by cohort age, gender, ethnicity, and heart
health at baseline. In stratified analyses, low-volume consumption was not
significantly protective for cohorts ages 55 years or younger at baseline (RR =
0.95, 95% CI [0.75, 1.21]), for studies controlling for heart health (RR = 0.87,
95% CI [0.71, 1.06]), or for higher quality studies (RR = 0.86, 95% CI [0.68,
1.09]). In studies in which the mean age was 55 years or younger at baseline,
there were significantly increased RRs for both former (RR = 1.45, 95% CI [1.08,
1.95]) and occasional drinkers (RR = 1.44, 95% CI [1.09, 1.89]) compared with
abstainers. CONCLUSIONS: Pooled analysis of all identified studies suggested an
association between alcohol use and reduced CHD risk. However, this association
was not observed in studies of those age 55 years or younger at baseline, in
higher quality studies, or in studies that controlled for heart health. The
appearance of cardio-protection among older people may reflect systematic
selection biases that accumulate over the life course.
PMID- 28499100
TI - Probing for Neuroadaptations to Unpredictable Stressors in Addiction:
Translational Methods and Emerging Evidence.
AB - Stressors clearly contribute to addiction etiology and relapse in humans, but our
understanding of specific mechanisms remains limited. Rodent models of addiction
offer the power, flexibility, and precision necessary to delineate the causal
role and specific mechanisms through which stressors influence alcohol and other
drug use. This review describes a program of research using startle potentiation
to unpredictable stressors that is well positioned to translate between animal
models and clinical research with humans on stress neuroadaptations in addiction.
This research rests on a solid foundation provided by three separate pillars of
evidence from (a) rodent behavioral neuroscience on stress neuroadaptations in
addiction, (b) rodent affective neuroscience on startle potentiation, and (c)
human addiction and affective science with startle potentiation. Rodent stress
neuroadaptation models implicate adaptations in corticotropin-releasing factor
and norepinephrine circuits within the central extended amygdala following
chronic alcohol and other drug use that mediate anxious behaviors and stress
induced reinstatement among drug-dependent rodents. Basic affective neuroscience
indicates that these same neural mechanisms are involved in startle potentiation
to unpredictable stressors in particular (vs. predictable stressors). We believe
that synthesis of these evidence bases should focus us on the role of
unpredictable stressors in addiction etiology and relapse. Startle potentiation
in unpredictable stressor tasks is proposed to provide an attractive and flexible
test bed to encourage tight translation and reverse translation between animal
models and human clinical research on stress neuroadaptations. Experimental
therapeutics approaches focused on unpredictable stressors hold high promise to
identify, repurpose, or refine pharmacological and psychosocial interventions for
addiction.
PMID- 28499103
TI - No Benefit of Light to Moderate Drinking for Mortality From Coronary Heart
Disease When Better Comparison Groups and Controls Included: A Commentary on Zhao
et al. (2017).
PMID- 28499104
TI - Robustness of the J-Shaped Association of Alcohol With Coronary Heart Disease
Risk.
PMID- 28499105
TI - Whether Low Volume Alcohol Use Is Cardio-Protective Is Important for Public
Health Policy So the Available Evidence Deserves Critical Analysis: The Authors
Respond.
PMID- 28499106
TI - Alcohol and Cigarette Use From Ages 23 to 55: Links With Health and Well-Being in
the Long-Term National Child Development Study.
AB - OBJECTIVE: Using longitudinal data from the National Child Development Study, an
ongoing study of a nationally representative British cohort born in 1958 (n =
9,137; 51% female), we examined how patterns of alcohol and cigarette use from
young adulthood (age 23) to midlife (age 55) are associated with health and well
being. METHOD: We first used a nonparametric multilevel latent class
specification to identify eight unique paths of alcohol and cigarette use from
ages 23 to 55, and then assessed how these long-term latent paths related to
overall health, heart problems, chronic illness, and quality of life at midlife.
RESULTS: Results show that adults who consistently drank within current U.K. low
risk guidelines (i.e., not exceeding 14 units of alcohol per week) and abstained
from smoking from young adulthood to midlife reported the best overall health and
well-being compared with latent paths involving steady, light to moderate
drinking and both current and prior smoking, increasing drinking and smoking, and
infrequent drinking/abstention. CONCLUSIONS: British adults who consistently
drank within new lower risk guidelines and abstained from smoking from young
adulthood to midlife reported the best overall health and well-being across
numerous indicators. However, apparent observed health benefits of stable low
dose alcohol use (vs. abstention) are weakened by the fact that by age 55 almost
all alcohol "abstainers" in the National Child Development Study sample were
former drinkers, and that respondents who followed infrequent drinking/abstention
paths were the mostly likely to report poor health, psychological distress, and
low educational qualifications in early adulthood.
PMID- 28499107
TI - Bias in Assessing Effects of Substance Use From Observational Studies: What Do
Longitudinal Data Tell Us? A Commentary on Staff and Maggs (2017).
PMID- 28499109
TI - Public Stigma Toward People With Drug Addiction: A Factorial Survey.
AB - OBJECTIVE: Stigmatizing attitudes toward people with a drug addiction have
detrimental effects on the lives of these people. However, the factors that
influence stigma toward people with a drug addiction have not yet been thoroughly
investigated, compared with the stigma of other mental illnesses. Based on
attribution theory, our experiment examined to what extent individual and
contextual characteristics of people with a drug addiction influence stigmatizing
attitudes toward people with a drug addiction. Moreover, we explored whether
respondent characteristics indicative of familiarity with addiction decrease
stigma toward people with a drug addiction. METHOD: We conducted a full factorial
survey of 2,857 respondents from a German online access panel who were from all
walks of life. We experimentally varied vignettes (29-design) that featured a
fictional person with an addiction. Stigmatizing beliefs, such as blame or fear,
were assessed using the Attribution Questionnaire (AQ-9). RESULTS: Different
attributes of people with a drug addiction and of the characteristics of their
addiction modulated stigma in ways that are mostly consistent with attribution
theory and related research. For example, female gender and younger age of people
with a drug addiction diminished several stigmatizing attitudes; greater duration
of addiction and social influence to use drugs increased them. Furthermore,
characteristics of respondents modulated stigma: women, younger respondents, and
those with higher education expressed less-stigmatizing responses than others.
CONCLUSIONS: The stigmatization of people with a drug addiction is influenced by
several factors, including characteristics of the stigmatized person, the
addiction, and the person holding stigmatizing attitudes. A better understanding
of the underlying mechanisms of these effects is needed to develop evidence-based
antistigma measures.
PMID- 28499108
TI - Alcohol Outcomes by Sexual Orientation and Race/Ethnicity: Few Findings of Higher
Risk.
AB - OBJECTIVE: This study sought to confirm a previously identified race by sexual
orientation interaction and to clarify men's alcohol-related risk by using an
expanded classification of sexual orientation. METHOD: We collapsed three waves
of National Alcohol Survey data, restricting the analytic sample to White (n =
5,689), Black (n = 1,237), and Latino (n = 1,549) men with complete information
on sexual orientation and alcohol use. Using self-reported sexual identity and
behavior, respondents were categorized as exclusively heterosexual (referent),
behaviorally discordant heterosexuals (i.e., heterosexual identity and same-sex
partners), or gay/bisexually identified men. We used multivariable logistic
regression to model lifetime alcohol dependence symptoms, lifetime drinking
related consequences, and past-year hazardous drinking, controlling for age,
education, employment, and relationship status and accounting for the complex
survey design. RESULTS: There was no difference in risk of past-year hazardous
drinking and lifetime drinking-related consequences between heterosexual,
behaviorally discordant heterosexual, and gay/bisexual men, independent of race/
ethnicity. Among Black men, behaviorally discordant heterosexuals had three-fold
higher odds of lifetime alcohol dependence symptoms than exclusively heterosexual
peers (aOR = 3.30, 95% CI [1.19, 9.18], p = .02). Gay/bisexual Latino men had
marginally significantly lower odds of lifetime alcohol dependence symptoms (aOR
= 0.36, 95% CI [0.12, 1.03], p = .06). CONCLUSIONS: There is little support for
broad statements of greater alcohol risk among gay/bisexual men; however, for
some subgroups and outcomes the direction and degree of risk depend on race/
ethnicity. Thus, this study underscores the importance of considering the
potential interaction of sexual orientation and race/ethnicity, which may
exacerbate or attenuate.
PMID- 28499110
TI - The Influence of Paternal Separation, Paternal History of Alcohol Use Disorder
Risk, and Early Substance Use on Offspring Educational Attainment by Young
Adulthood.
AB - OBJECTIVE: This study aimed to determine the associations among paternal alcohol
problems, separation, and educational attainment in European American and African
American offspring and whether offspring early alcohol/tobacco/marijuana use
influenced these associations. METHOD: Families with offspring ages 13-19 years
at intake were selected from state birth records and screened by telephone to
determine high-risk or low-risk status (with/without paternal heavy drinking).
Families of men with two or more driving-under-the-influence offenses were added
as a very-high-risk group. Data from 340 African American and 288 European
American offspring who were not enrolled in school at their last interview were
analyzed. Educational attainment was modeled as less than high school, high
school only (reference category), and some college or higher. Separation was
defined as offspring report of not having lived continuously in the same
household with their biological father from birth to age 14. Analyses were
stratified by race. RESULTS: In European Americans, neither family risk status
nor early alcohol/tobacco/marijuana use was associated with educational outcomes.
However, paternal separation significantly elevated the likelihood of not
completing high school in all models (relative risk ratios [RRRs] = 6.0-8.1, p
<.001). For African American offspring, likelihoods of high school noncompletion
were elevated marginally for paternal separation in only one model, but
significantly for early marijuana use (RRRs = 2.8-3.2, p < .05). Very-high-risk
status significantly reduced the likelihood of post-high school education in an
adjusted model (RRR = 0.4, p < .05). CONCLUSIONS: High school noncompletion was
significantly associated with paternal separation in European Americans and with
early marijuana use in African American offspring. In addition, very-high-risk
status reduced the likelihood of post-high school education in African American
offspring only, suggesting that research with ethnically diverse samples yields
important differences when examining outcomes of both separation and substance
use on offspring education.
PMID- 28499111
TI - Late-Life Drinking Problems: The Predictive Roles of Drinking Level vs. Drinking
Pattern.
AB - OBJECTIVE: Research on late-middle-aged and older adults has focused primarily on
average level of alcohol consumption, overlooking variability in underlying
drinking patterns. The purpose of the present study was to examine the
independent contributions of an episodic heavy pattern of drinking versus a high
average level of drinking as prospective predictors of drinking problems. METHOD:
The sample comprised 1,107 adults ages 55-65 years at baseline. Alcohol
consumption was assessed at baseline, and drinking problems were indexed across
20 years. We used prospective negative binomial regression analyses controlling
for baseline drinking problems, as well as for demographic and health factors, to
predict the number of drinking problems at each of four follow-up waves (1, 4,
10, and 20 years). RESULTS: Across waves where the effects were significant, a
high average level of drinking (coefficients of 1.56, 95% CI [1.24, 1.95]; 1.48,
95% CI [1.11, 1.98]; and 1.85, 95% CI [1.23, 2.79] at 1, 10, and 20 years) and an
episodic heavy pattern of drinking (coefficients of 1.61, 95% CI [1.30, 1.99];
1.61, 95% CI [1.28, 2.03]; and 1.43, 95% CI [1.08, 1.90] at 1, 4, and 10 years)
each independently increased the number of drinking problems by more than 50%.
CONCLUSIONS: Information based only on average consumption underestimates the
risk of drinking problems among older adults. Both a high average level of
drinking and an episodic heavy pattern of drinking pose prospective risks of
later drinking problems among older adults.
PMID- 28499113
TI - Social and Individual-Level Predictors of Alcohol Use Initiation and Escalation:
Replicating and Extending Tests of Differential Effects.
AB - OBJECTIVE: Although alcohol use is considered a developmental phenomenon, there
is a relative dearth of studies disaggregating predictors of alcohol use
initiation versus early escalation of drinking. One perspective that has emerged
is that social levels of influence may be relevant for the initiation of
drinking, whereas individual levels of influence may be relevant for the early
escalation in level of drinking among initiators, which we refer to as the
specificity hypothesis. METHOD: A sample of alcohol-naive youth (n = 944; mean
age = 12.16 years, SD = 0.96) was prospectively assessed for 3 years, spanning
six waves of data collection. RESULTS: Both social (parental conflict, perceived
prevalence of peer drinking) and individual-level (higher sensation seeking)
variables uniquely predicted increases in the likelihood of alcohol initiation.
Likewise, both social (perceived descriptive norms of peer drinking) and
individual-level (lower school grades, higher sensation seeking) variables
uniquely predicted escalation in level of drinking among initiators (although
only marginally for sensation seeking). CONCLUSIONS: Overall, there was little
support for the specificity hypothesis. Our findings suggest that to assume that
social and individual-level processes differentially predict drinking outcomes
may be a false dichotomy. Theoretical work may benefit from drawing from
developmental models emphasizing the interplay between individual and
environmental factors in the prediction of the early development of drinking. The
emergence of drinking behaviors is likely to result from a developmental cascade
of interacting variables that make the ontogeny of drinking unlikely to emerge
from a single class of variables.
PMID- 28499112
TI - Polygenic Risk, Personality Dimensions, and Adolescent Alcohol Use Problems: A
Longitudinal Study.
AB - OBJECTIVE: Alcohol use problems are common during adolescence and can predict
serious negative outcomes in adulthood, including substance dependence and
psychopathology. The current study examines the notion that alcohol use problems
are driven by polygenic influences and that genetic influences may indirectly
affect alcohol use problems through multiple pathways of risk, including
variations in personality. METHOD: We used a genome-wide approach to examine
associations between genetic risk for alcohol use problems, personality
dimensions, and adolescent alcohol use problems in two separate longitudinal
population-based samples, the Finnish Twin Cohort (FinnTwin12) and the Avon
Longitudinal Study of Parents and Children (ALSPAC). Participants were 1,035
young adults from FinnTwin12 and 3,160 adolescents from ALSPAC. Polygenic risk
scores (PRS) were calculated for ALSPAC using genome-wide association results (on
alcohol dependence symptoms as defined by the Diagnostic and Statistical Manual
of Mental Disorders, Fourth Edition) from FinnTwin12. A parallel multiple
mediator model was tested to examine whether the association between PRS and
alcohol use problems assessed at age 16 could be explained by variations in
personality dimensions assessed at age 13, including sensation seeking and
negative emotionality. RESULTS: PRS were marginally predictive of age 16 alcohol
use problems; this association was partially mediated by sensation seeking.
Polygenic variation underlying risk for alcohol use problems may directly
influence the effects of sensation seeking, which in turn influence the
development of alcohol use problems in later adolescence. CONCLUSIONS: These
findings contribute to the increasing evidence regarding the salience of
sensation seeking during early adolescence as a potential constituent in the risk
pathway underlying the development of alcohol use problems.
PMID- 28499114
TI - Fathers' Alcohol and Cannabis Use Disorder and Early Onset of Drug Use by Their
Children.
AB - OBJECTIVE: The unique influence of fathers' alcohol and cannabis use disorder on
children's onset of use of these same substances has been rarely studied. A clear
understanding of family history in this context is important for the development
of family-based prevention initiatives aimed at delaying the onset of substance
use among children. METHOD: Prospective, longitudinal, and intergenerational data
on 274 father-child dyads were used. Logistic regression models were estimated to
assess the association between fathers' lifetime incidence of an alcohol and
cannabis use disorder and children's onset of use of these same substances at or
before age 15. RESULTS: The children of fathers who met the criteria for a
lifetime cannabis use disorder were more likely to initiate use of alcohol (odds
ratio = 6.71, 95% CI [1.92, 23.52]) and cannabis (odds ratio = 8.13, 95% CI
[2.07, 31.95]) by age 15, when background covariates and presence of a lifetime
alcohol use disorder were controlled for. No unique effect of fathers' alcohol
use disorder on children's onset of alcohol and cannabis use was observed.
CONCLUSIONS: Fathers' lifetime cannabis use disorder had a unique and robust
association with children's uptake of alcohol and cannabis by age 15. Future
research is needed to identify the mediating mechanisms that link fathers'
disorder with children's early onset.
PMID- 28499115
TI - A Comparison of Long- vs. Short-Term Recall of Substance Use and HIV Risk
Behaviors.
AB - OBJECTIVE: The Timeline Follow-back (TLFB) questionnaire has become a pre-eminent
tool in substance use and human immunodeficiency virus (HIV) risk research,
allowing researchers to assess fine-grained changes in risk behavior over long
periods. However, data on accuracy of recall over long (12-month) periods are
sparse, especially combined data on HIV risk and substance use from post
treatment samples. Studies on the development of substance use and HIV risk stand
to benefit from data on the accurate recall of such behavior over longer
retroactive spans of time. METHOD: The present study offers data on the test
retest reliability of current TLFB assessment versus 6- and 12-month delayed TLFB
assessment, using a post-treatment sample (n = 50). RESULTS: Long-term
reliability of TLFB data on HIV risk was predominantly good to excellent, with 13
of 20 assessed variables in that range. TLFB data on substance use was similar,
with 22 of 26 variables resulting in good/excellent reliability. CONCLUSIONS: Our
findings support the notion that, notable exceptions aside, the TLFB may be
effectively used to assess retroactive HIV risk and substance use in periods of
12 months.
PMID- 28499116
TI - Postgraduate Alcohol and Other Drug Practitioner Training in New Zealand:
Significant Influences.
AB - OBJECTIVE: The purpose of this article is to present a case study of the
evolution of postgraduate-level training programs for alcohol and other drug
(AOD) practitioners provided by two universities in New Zealand. METHOD: The case
study compiles details on relevant treatment contexts and systems in New Zealand
and key milestones and significant developments in postgraduate AOD practitioner
programs in two locations over a 30-year period. The details were compiled by the
authors, all of whom were closely involved with the development of the training
programs. RESULTS: The key ingredients for success that were identified included
a focus on specialized learning overlaying generic undergraduate professional
training; a core commitment to practice oriented teaching; investment in the
training by government bodies; and the parallel emergence of professional bodies,
registration systems, and collaborative relationships across agencies. In a small
country, the two programs have enabled 345 students to obtain specialist
postgraduate qualifications in AOD practice over a 10-year period. CONCLUSIONS:
Little could have been achieved without ongoing cooperation between education
providers, government agencies, and AOD services. This history may be of interest
to those in other locations attempting to establish nation- or statewide
approaches to AOD practitioner training.
PMID- 28499117
TI - Conclusion Overreach in Alcohol and Pregnancy Article: The Authors Reply.
PMID- 28499118
TI - Ethanol Concentration of Traditional Alcoholic Beverages in Northern Tanzania.
PMID- 28499119
TI - Identification of emotions in mixed disgusted-happy faces as a function of
depressive symptom severity.
AB - BACKGROUND AND OBJECTIVES: Interpersonal difficulties are common in depression,
but their underlying mechanisms are not yet fully understood. The role of
depression in the identification of mixed emotional signals with a direct
interpersonal value remains unclear. The present study aimed to clarify this
question. METHODS: A sample of 39 individuals reporting a broad range of
depression levels completed an emotion identification task where they viewed
faces expressing three emotional categories (100% disgusted and 100% happy faces,
as well as their morphed 50% disgusted - 50% happy exemplars). Participants were
asked to identify the corresponding depicted emotion as "clearly disgusted",
"mixed", or "clearly happy". RESULTS: Higher depression levels were associated
with lower identification of positive emotions in 50% disgusted - 50% happy
faces. LIMITATIONS: The study was conducted with an analogue sample reporting
individual differences in subclinical depression levels. Further research must
replicate these findings in a clinical sample and clarify whether differential
emotional identification patterns emerge in depression for different mixed
negative-positive emotions (sad-happy vs. disgusted-happy). CONCLUSIONS:
Depression may account for a lower bias to perceive positive states when
ambiguous states from others include subtle signals of social threat (i.e.,
disgust), leading to an under-perception of positive social signals.
PMID- 28499120
TI - Characterising bias in regulatory risk and decision analysis: An analysis of
heuristics applied in health technology appraisal, chemicals regulation, and
climate change governance.
AB - In many environmental and public health domains, heuristic methods of risk and
decision analysis must be relied upon, either because problem structures are
ambiguous, reliable data is lacking, or decisions are urgent. This introduces an
additional source of uncertainty beyond model and measurement error - uncertainty
stemming from relying on inexact inference rules. Here we identify and analyse
heuristics used to prioritise risk objects, to discriminate between signal and
noise, to weight evidence, to construct models, to extrapolate beyond datasets,
and to make policy. Some of these heuristics are based on causal generalisations,
yet can misfire when these relationships are presumed rather than tested (e.g.
surrogates in clinical trials). Others are conventions designed to confer
stability to decision analysis, yet which may introduce serious error when
applied ritualistically (e.g. significance testing). Some heuristics can be
traced back to formal justifications, but only subject to strong assumptions that
are often violated in practical applications. Heuristic decision rules (e.g.
feasibility rules) in principle act as surrogates for utility maximisation or
distributional concerns, yet in practice may neglect costs and benefits, be based
on arbitrary thresholds, and be prone to gaming. We highlight the problem of rule
entrenchment, where analytical choices that are in principle contestable are
arbitrarily fixed in practice, masking uncertainty and potentially introducing
bias. Strategies for making risk and decision analysis more rigorous include:
formalising the assumptions and scope conditions under which heuristics should be
applied; testing rather than presuming their underlying empirical or theoretical
justifications; using sensitivity analysis, simulations, multiple bias analysis,
and deductive systems of inference (e.g. directed acyclic graphs) to characterise
rule uncertainty and refine heuristics; adopting "recovery schemes" to correct
for known biases; and basing decision rules on clearly articulated values and
evidence, rather than convention.
PMID- 28499121
TI - Molecular characterization of O157:H7, O26:H11 and O103:H2 Shiga toxin-producing
Escherichia coli isolated from dairy products.
AB - Pathogenic Shiga toxin-producing E. coli (STEC) are recognized worldwide as
environment and foodborne pathogens which can be transmitted by ingestion of
ready-to-eat food such as raw milk-derived products. STEC show a prevalence rate
in dairy products of 0.9%, yet comparably few outbreaks have been related to
dairy products consumption. In this study, we used rt-qPCR to identify the
virulence potential of O157, O26 and O103 STEC strains isolated from raw-milk
dairy products by analyzing virulence-related gene frequencies and associations
with O-island (OI) 44, OI-48, OI-50, OI-57, OI-71 and OI-122. Results showed that
100% of STEC strains investigated harbored genes associated with EHEC-related
virulence profile patterns (eae and stx, with either espK, espV, ureD and/or
Z2098). We also found similarities in virulence-related gene content between
O157:H7 and O103:H2 dairy and non-dairy STEC strains, especially isolates from
human cases. The O26:H11-serotype STEC strains investigated harbor the arcA
allele 2 gene associated with specific genetic markers. These profiles are
associated with high-virulence seropathotype-A STEC. However, the low frequency
of stx2 gene associated with absence of other virulence genes in dairy isolates
of O26:H11 remains a promising avenue of investigation to estimate their real
pathogenicity. All O26:H11 attaching-effacing E. coli (AEEC) strains carried
CRISPRO26:H11SP_O26_E but not genetic markers espK, espV, ureD and/or Z2098
associated with the emerging potentially high-virulence "new French clone". These
strains are potentially as "EHEC-like" strains because they may acquire (or have
lost) stx gene. In this study, O157:H7, O103:H2 and O26:H11 STEC strains isolated
from dairy products were assigned as potential pathogens. However, research now
needs to investigate the impact of dairy product environment and dairy processing
on the expression of their pathogenicity.
PMID- 28499122
TI - EMD-DWT based transform domain feature reduction approach for quantitative multi
class classification of breast lesions.
AB - Using a large set of ultrasound features does not necessarily ensure improved
quantitative classification of breast tumors; rather, it often degrades the
performance of a classifier. In this paper, we propose an effective feature
reduction approach in the transform domain for improved multi-class
classification of breast tumors. Feature transformation methods, such as
empirical mode decomposition (EMD) and discrete wavelet transform (DWT), followed
by a filter- or wrapper-based subset selection scheme are used to extract a set
of non-redundant and more potential transform domain features through
decorrelation of an optimally ordered sequence of N ultrasonic bi-modal (i.e.,
quantitative ultrasound and elastography) features. The proposed transform domain
bi-modal reduced feature set with different conventional classifiers will
classify 201 breast tumors into benign-malignant as well as BI-RADS?3, 4, and 5
categories. For the latter case, an inadmissible error probability is defined for
the subset selection using a wrapper/filter. The classifiers use train truth from
histopathology/cytology for binary (i.e., benign-malignant) separation of tumors
and then bi-modal BI-RADS scores from the radiologists for separating malignant
tumors into BI-RADS category 4 and 5. A comparative performance analysis of
several widely used conventional classifiers is also presented to assess their
efficacy for the proposed transform domain reduced feature set for classification
of breast tumors. The results show that our transform domain bimodal reduced
feature set achieves improvement of 5.35%, 3.45%, and 3.98%, respectively, in
sensitivity, specificity, and accuracy as compared to that of the original domain
optimal feature set for benign-malignant classification of breast tumors. In
quantitative classification of breast tumors into BI-RADS categories?3, 4, and 5,
the proposed transform domain reduced feature set attains improvement of 3.49%,
9.07%, and 3.06%, respectively, in likelihood of malignancy and 4.48% in
inadmissible error probability compared to that of the original domain optimal
subset. In summary, the construction of a transform domain reduced feature set by
extracting complementary information from a large set of available bi-modal
features and use of qualitative bi-modal BI-RADS can contribute to improved
quantitative classification of breast tumors and thereby help reduce the number
of unnecessary biopsies, securing a nearly minimum chance of a life-endangering
diagnosis.
PMID- 28499123
TI - Self-action of propagating and standing Lamb waves in the plates exhibiting
hysteretic nonlinearity: Nonlinear zero-group velocity modes.
AB - An analytical theory accounting for the influence of hysteretic nonlinearity of
micro-inhomogeneous plate material on the Lamb waves near the S1 zero group
velocity point is developed. The theory predicts that the main effect of the
hysteretic quadratic nonlinearity consists in the modification of the frequency
and the induced absorption of the Lamb modes. The effects of the nonlinear self
action in the propagating and standing Lamb waves are expected to be,
respectively, nearly twice and three times stronger than those in the plane
propagating acoustic waves. The theory is restricted to the simplest hysteretic
nonlinearity, which is influencing only one of the Lame moduli of the materials.
However, possible extensions of the theory to the cases of more general
hysteretic nonlinearities are discussed as well as the perspectives of its
experimental testing. Applications include nondestructive evaluation of micro
inhomogeneous and cracked plates.
PMID- 28499124
TI - Peri-ultrasound for modeling linear and nonlinear ultrasonic response.
AB - The objective of this paper is to introduce a novel fast modeling tool called
peri-ultrasound for linear/nonlinear ultrasonic wave propagation modeling. This
modeling approach is based on peridynamic theory. It does not require monitoring
of the crack clapping phenomenon or artificially changing the stiffness of the
element when two surfaces of the crack come in contact. Peri-ultrasound tool
enables us to detect the material nonlinearity in very early stages of crack
growth. Nonlinear ultrasonic behavior could be nicely modeled by the proposed
peri-ultrasound tool. It is investigated how the material nonlinearity is
affected by the presence of thin and thick cracks. From the normalized spectral
plots the degree of material nonlinearity can be measured by extracting a feature
called sideband peak count (SPC). Structures containing a thin crack show
noticeable increase in their nonlinear behavior.
PMID- 28499125
TI - Statistics associated with the scattering of ultrasound from microstructure.
AB - The spatial statistics of an ensemble of waveforms containing ultrasonic
scattering from microstructure are investigated. The standard deviation of the
waveforms is of primary interest, because it is related to the maximum scattering
amplitudes in the extreme value statistics theory. Further statistical measures
are employed to define theoretical confidence bounds, which bound the
experimentally calculated maximum amplitude when a finite number of waveforms are
included in the ensemble. These statistical measures are applied in conjunction
with a previously developed ultrasonic backscatter model. It is validated through
ultrasonic scattering measurements performed on a stainless-steel pipe sample.
These considerations are important for forward models related to the probability
of detection (POD) of defects and inverse models used for characterization of
polycrystalline microstructures.
PMID- 28499127
TI - 3D-printed scaffolds with synergistic effect of hollow-pipe structure and
bioactive ions for vascularized bone regeneration.
AB - Segmental bone regeneration remains a considerable challenge due to the
associated low degree of vascularization. To solve this problem, in this study,
hollow-pipe-packed silicate bioceramic (BRT-H) scaffolds are fabricated using a
coaxial three-dimensional (3D) printing technique. Based on a modified core/shell
printer nozzle and a modulated viscoelastic bioceramic paste, hollow struts with
an external diameter of 1 mm and internal dimeter of 500 MUm can be directly
printed, yielding a compressive strength of the BRT-H scaffolds as high as 26
MPa. Apart from the effects on osteogenesis, the bioactive ions released from the
BRT scaffolds can also facilitate angiogenesis via inducing endothelial cell
migration. More importantly, the hollow pipes not only significantly promote the
rapid infiltration of host blood vessels into the channels but also exhibit great
advantages for the delivery of stem cells and growth factors to further enhance
tissue regeneration. When used for the regeneration of rabbit radius segmental
defects, radiological and histological findings indicate that the BRT-H scaffolds
can enhance early vascularization and later bone regeneration and remodeling.
Taken together, the hollow pipes and the ionic products from BRT-H scaffolds have
a synergistic effect on enhancing vascularized bone regeneration.
PMID- 28499126
TI - Control of Tumor Initiation by NKG2D Naturally Expressed on Ovarian Cancer Cells.
AB - Cancer cells may co-opt the NKG2D lymphocyte receptor to complement the presence
of its ligands for autonomous stimulation of oncogenic signaling. Previous
studies raise the possibility that cancer cell NKG2D may induce high malignancy
traits, but its full oncogenic impact is unknown. Using epithelial ovarian cancer
as model setting, we show here that ex vivo NKG2D+ cancer cells have stem-like
capacities, and provide formal in vivo evidence linking NKG2D stimulation with
the development and maintenance of these functional states. NKG2D+ ovarian cancer
cell populations harbor substantially greater capacities for self-renewing in
vitro sphere formation and in vivo tumor initiation in immunodeficient (NOD scid
gamma) mice than NKG2D- controls. Sphere formation and tumor initiation are
impaired by NKG2D silencing or ligand blockade using antibodies or a newly
designed pan ligand-masking NKG2D multimer. In further support of
pathophysiological significance, a prospective study of 47 high-grade serous
ovarian cancer cases revealed that the odds of disease recurrence were
significantly greater and median progression-free survival rates higher among
patients with above and below median NKG2D+ cancer cell frequencies,
respectively. Collectively, our results define cancer cell NKG2D as an important
regulator of tumor initiation in ovarian cancer and presumably other malignancies
and thus challenge current efforts in immunotherapy aimed at enhancing NKG2D
function.
PMID- 28499128
TI - Stress induced by heavy metals on breeding of magpie (Pica pica) from central
Iran.
AB - The aim of this study was to address the impacts of some heavy metals (Cd, Pb,
Zn, Ni and Cu) contamination on laying behavior, egg quality and breeding
performance of Pica pica in north of Isfahan Province, Iran. During the breeding
season of 2013, magpie's egg content and eggshell as well as nestling excrements
and feathers were collected and total concentrations of heavy metals were
measured by ICP-OES. Except for Zn in nestling feathers, the significantly higher
concentrations of heavy metals were observed in nestling excrements than other
samples. Also, comparison of heavy metals concentrations in egg content and
eggshell showed that egg content had significantly higher concentrations of Zn
and Pb, instead eggshell had significantly higher amount of Cu and Cd. Except for
Cu, all heavy metals concentrations in eggshell had a negative relationship with
morphological characters; and also concentration of Cu in egg content showed a
significantly negative correlation with egg weight and volume. The most of heavy
metals in nestling feathers and excrements had strongly positive correlations
with each other. Also all heavy metals levels in eggshell and egg content had
significantly positive correlations (except for Cu). Unhatched eggs had
significantly lower weight but also greater levels of Zn, Cd, and Pb, than
randomly collected eggs. No significant differences were observed for
morphometric measurements of eggs between different sites, however, a decreased
gradient was observed in egg volume toward the brick kiln site. Samples collected
in brick kiln site accumulated higher concentrations of heavy metals than other
sites. Although numbers of clutch size in brick kiln site were significantly
higher than other sites, however, other breeding variable were lower than other
sites. It can be suggested that ecosystem contamination may be caused to decrease
the reproduction rate of Pica pica in brick kiln, probably by laying more poor
quality eggs per clutch and nestling mortality.
PMID- 28499129
TI - Occurrence of antimicrobial resistance bacteria in the Yodo River basin, Japan
and determination of beta-lactamases producing bacteria.
AB - Antimicrobial resistant bacteria are widespread in aquatic environments. The aim
of the present study was to obtain information on the occurrence of bacteria with
antimicrobial resistance and their multiple antimicrobial resistance (MAR)
patterns in a river basin in Japan. In addition, the occurrence of fecal bacteria
producing extended-spectrum beta-lactamases (ESBLs) and metallo-beta-lactamase
(MBL) in the aquatic environment was determined. Among the Escherichia coli
isolates recovered from river samples upstream, 55% isolates were resistant to at
least one antimicrobial and 18% were MAR. Among the E. coli isolates recovered
from wastewater treatment plant (WWTP) effluent samples, 74% isolates were
resistant to at least one antimicrobial and 46% were MAR. These findings suggest
that the presence of WWTP effluent will increase the degree of contamination with
MAR in the aquatic environment. Among the ampicillin-resistant isolates recovered
from river samples, 21% isolates were judged as ESBL-producing and none (0%) was
judged as MBL-producing. Among the ampicillin-resistant isolates recovered from
WWTP effluent samples, 21% were judged as ESBL-producing and 1% was judged as MBL
producing. As for the hospital wastewater samples, 48% were judged as ESBL
producing and 3% were judged as MBL-producing. The percentage of ESBLs and MBL
production was highest in hospital wastewater samples. All of the ESBL-producing
isolates detected had resistance to ampicillin, cephazolin, and cefpodoxime and
many ESBL-producers had resistance not only to beta-lactams but also to other
kinds of antimicrobials such as aminoglycosides and quinolones. The frequency of
detection of MBL-producers was much lower than that of ESBL-producers and MBL
producers were not detected in the river samples. However, the detection in WWTP
effluent samples indicated that bacteria with MBL were present downstream of the
WWTP at low concentrations. Thus, ESBLs and MBL have already been spread around
aquatic environments.
PMID- 28499130
TI - Extracorporeal membrane oxygenation (ECMO) as a treatment strategy for severe
acute respiratory distress syndrome (ARDS) in the low tidal volume era: A
systematic review.
AB - OBJECTIVE: To evaluate the hospital survival in patients with severe ARDS managed
with ECMO and low tidal volume ventilation as compared to patients managed with
low tidal volume ventilation alone. METHODS: Electronic databases were searched
for studies of at least 10 adult patients with severe ARDS comparing the use of
ECMO with low tidal volume ventilation to mechanical ventilation with a low tidal
volume alone. Only studies reporting hospital or ICU survival were included. All
identified studies were assessed independently by two reviewers. RESULTS: Of 1782
citations, 27 studies (n=1674) met inclusion criteria. Hospital survival for ECMO
patients ranged from 33.3 to 86%, while survival with conventional therapy ranged
from 36.3 to 71.2%. Five studies were identified with appropriate control groups
allowing comparison, but due to the high degree of variability between studies
(I2=63%), their results could not be pooled. Two of these studies demonstrated a
significant difference, both favouring ECMO over conventional therapy.
CONCLUSION: Given the lack of studies with appropriate control groups, our
confidence in a difference in outcome between the two therapies remains weak.
Future studies on the use of ECMO for severe ARDS are needed to clarify the role
of ECMO in this disease.
PMID- 28499131
TI - Polyphyly in the Thecate Amoeba Genus Lecythium (Chlamydophryidae, Tectofilosida,
Cercozoa), Redescription of its Type Species L. hyalinum, Description of L.
jennyae sp. nov. and the Establishment of Fisculla gen. nov. and Fiscullidae fam.
nov.
AB - Although testate amoebae have attracted great interest of protistologists for
more than a century, some groups, especially those with a hyaline, organic test
(=theca) are still poorly known. One of those is the genus Lecythium Hertwig et
Lesser, 1874. Only recently Lecythium spp. were characterized by morphological
and molecular means, but data on the type species Lecythium hyalinum Hertwig et
Lesser, 1874, was still lacking. In this study, we screened for L. hyalinum in
freshwater samples of Germany and the Netherlands. Four different isolates of L.
hyalinum and one novel species were cultured and characterized by light
microscopy. Phylogenetic analyses based on the small ribosomal subunit (SSU) RNA
gene show that the genus Lecythium forms two robust clades, one forming a sister
group to the Rhizaspididae/Pseudodifflugiidae clade (Tectofilosida), the other
branching within 'Novel Clade 4' (Tectofilosida). We untangle this polyphyly by
establishing Fisculla gen. nov. and the Fiscullidae fam. nov. for the former of
these two clades.
PMID- 28499133
TI - Value of digit ratio 2D:4D, a biomarker of prenatal hormone exposure, is stable
across the menstrual cycle.
AB - Digit ratio (2D:4D) is used as a marker of prenatal hormone exposure and,
consequently, as a predictor of many characteristics throughout a woman's
lifespan. A previous study has suggested that values of 2D:4D vary across
menstrual cycles and further questioned the reliability of a single measurement
of 2D:4D among cycling women, while another study failed to confirm these
results. However, these studies estimated the timing of cycle phases based on a
date of menstruation reported by participants and also had small sample sizes.
For our study, we evaluated potential changes in 2D:4D values across a menstrual
cycle in a group of women among whom the phases of the menstrual cycle were
determined by hormonal (luteinizing hormone based) ovulation tests. We studied 32
naturally cycling women aged 22-37 from rural Poland. Lengths of second and
fourth digits were measured based on scans of both hands taken three times (i.e.
in the follicular phase, peri-ovulatory phase and luteal phase of the cycle) for
each participant. No differences in 2D:4D value across the menstrual cycle were
detected either when right-hand, left-hand, and mean 2D:4D for both hands were
analysed, nor when difference in the 2D:4D value between hands (Dleft-right) was
evaluated. We documented that 2D:4D is independent of the phase of the menstrual
cycle and these findings suggest that among naturally cycling women, a value of
2D:4D can be reliably obtained from measurements taken during any day of the
menstrual cycle.
PMID- 28499134
TI - Digit ratio (2D:4D) and postoperative pain perception.
AB - BACKGROUNDS: It has not been established whether sex differences in pain
perception are influenced by prenatal sex hormones. Digit ratio as an indicator
of prenatal hormone exposure can be used as a simple measure of the influence of
prenatal hormones on pain sensitivity or perception in adulthood. OBJECTIVE: The
aim of this study was to determine a correlation between the 2D:4D ratio and pain
perception in the postoperative period after rhinoplasty. METHOD: A prospective
cohort study of 100 patients (50 women of the mean age of 30.74+/-8.09years and
50 men of the mean age of 30.98+/-10.86years) who underwent posttraumatic
rhinoplasty due to the nose trauma in Plastic, Reconstructive and Aesthetic
Surgery Clinic. The following measurements were taken the day before a surgery:
body height, waist and hip circumference, II and IV digits' lengths and body
weight. All subjects filled in a questionnaire including 0-10-point VAS scales to
assess postoperative pain 1h after an operation (AO), 6h AO, 12h AO, 24h AO and
48h AO. RESULTS: Women with low 2D:4D reported significantly more pain 1h after
an operation than women with high 2D:4D. Similar correlation was observed for low
2D:4D in women 48h AO. In men, low 2D:4D was associated with lower postoperative
pain 12h AO (p=0.029). CONCLUSION: In conclusion, we showed that low 2D:4D in
women was associated with high postoperative pain, and low right 2D:4D in men was
associated with low postoperative pain. This may suggest that intrauterine
estrogen exposure makes women more resistant to pain.
PMID- 28499132
TI - Multiple Dictyostelid Species Destroy Biofilms of Klebsiella oxytoca and Other
Gram Negative Species.
AB - Dictyostelids are free-living phagocytes that feed on bacteria in diverse
habitats. When bacterial prey is in short supply or depleted, they undergo
multicellular development culminating in the formation of dormant spores. In this
work, we tested isolates representing four dictyostelid species from two genera
(Dictyostelium and Polysphondylium) for the potential to feed on biofilms
preformed on glass and polycarbonate surfaces. The abilities of dictyostelids
were monitored for three hallmarks of activity: 1) spore germination on biofilms,
2) predation on biofilm enmeshed bacteria by phagocytic cells and 3)
characteristic stages of multicellular development (streaming and
fructification). We found that all dictyostelid isolates tested could feed on
biofilm enmeshed bacteria produced by human and plant pathogens: Klebsiella
oxytoca, Pseudomonas aeruginosa, Pseudomonas syringae, Erwinia amylovora 1189
(biofilm former) and E. amylovora 1189 Deltaams (biofilm deficient mutant).
However, when dictyostelids were fed planktonic E. amylovora Deltaams the
bacterial cells exhibited an increased susceptibility to predation by one of the
two dictyostelid strains they were tested against. Taken together, the
qualitative and quantitative data presented here suggest that dictyostelids have
preferences in bacterial prey which affects their efficiency of feeding on
bacterial biofilms.
PMID- 28499135
TI - Pain threshold, tolerance and intensity in adolescents born very preterm or with
low birth weight.
AB - BACKGROUND: Data on long-term consequences of neonatal pain is limited. AIM: To
assess whether perinatal factors, later pain experience and pain coping
strategies are associated with altered pain threshold, pain tolerance and pain
intensity in adolescents born preterm. STUDY DESIGN: Observational, longitudinal
study (Project on Preterm and SGA-infants, POPS-19). SUBJECTS: We analyzed data
of 412 adolescents at the age of 19years, who were born at a gestational
age<32weeks or with a birth weight<1500g. OUTCOME MEASURES: Participants
performed a standardized cold pressor test to assess pain threshold, tolerance
and intensity. Furthermore, they completed a pain coping questionnaire (PCQ).
RESULTS: In univariate analysis, female gender and necrotizing enterocolitis
(NEC) were associated with lower pain tolerance, indicated by reaching the
ceiling time of 180s in ice water (females 19% vs males 29%, NEC 7% vs no NEC
25%). Female gender was associated with higher pain intensity (mean difference
0.58; 95%CI 0.21; 0.95) and lower pain threshold (log rank test p 0.007). In a
multivariate Cox regression analyses, emotion focused avoidance pain coping style
was significantly associated with lower pain threshold (hazard ratio HR 1.38;
95%CI 1.02; 1.87) and pain tolerance (HR 1.72; 95%CI 1.21; 2.42). NEC was
significantly associated with lower pain threshold (HR 1.47; 95%CI 1.01; 2.14)
and pain tolerance (HR 1.63; 95%CI 1.09; 2.41). CONCLUSION: In adolescence,
maladaptive pain coping strategy was associated with lower pain threshold, pain
tolerance and higher pain intensity. NEC was associated with altered pain
response in adolescents born preterm.
PMID- 28499136
TI - A novel tool for the identification of correlations in medical data by faceted
search.
AB - This work focuses on the integration of multifaceted extensive data sets (e.g.
laboratory values, vital data, medications) and partly unstructured medical data
such as discharge letters, diagnostic reports, clinical notes etc. in a research
database. Our main application is an integrated faceted search in nephrology
based on information extraction results. We describe the details of the
application of transplant medicine and the resulting technical architecture of
the faceted search application.
PMID- 28499137
TI - A comparison of the ground reaction force frequency content during rearfoot and
non-rearfoot running patterns.
AB - Running with a non-rearfoot pattern has been claimed to reduce injury risk
because the impact peak in the vertical ground reaction force (GRF) is visually
absent in the time-domain compared with a rearfoot pattern. However, running
results in a rapid deceleration of the lower extremity segments immediately
following initial contact with the ground, regardless of footfall pattern.
Therefore, the frequency content of the GRF is expected to contain evidence of
this collision. The purpose of the present study was to characterize the waveform
components of the GRF generated during the impact phase by habitual rearfoot and
habitual non-rearfoot pattern groups using the continuous wavelet transform.
Twenty rearfoot and 20 non-rearfoot participants ran over-ground at a
standardized speed with their habitual footfall pattern. The continuous wavelet
transform was performed on the resultant GRF vector and the vertical GRF. GRF
signals generated by the non-rearfoot pattern group during early stance had
maximum signal power of 15.4+/-9.1Hz occurring at 23.1+/-6.3% of stance, which is
within the 10-20Hz range previously associated with impact in rearfoot runners.
Maximum signal power occurred earlier in the impact phase (11.5+/-1.5%) and with
a higher frequency (27.2+/-3.9Hz) in the rearfoot pattern group verses the non
rearfoot pattern group (P<0.05). While the impact force transient may not appear
as a prominent feature within the time-domain GRF with a non-rearfoot pattern,
the results indicate that both footfall patterns generate frequencies associated
with the impact peak in the resultant and vertical GRF.
PMID- 28499138
TI - Human pegivirus-1 in the CSF of patients with HIV-associated neurocognitive
disorder (HAND) may be derived from blood in highly viraemic patients.
AB - BACKGROUND: Human pegivirus-1 (HPgV-1) infection in the brain has not been
extensively examined and its association with disease remains unconfirmed. In a
high throughput sequencing study to look for infectious agents that could play a
role in HIV-associated neurocognitive disorder (HAND), this virus was detected in
3 of 8 CSF samples. OBJECTIVES: To determine the significance of this finding,
additional patients were screened and the viral load and viral diversity in blood
and CSF were examined. STUDY DESIGN: Nested PCR of the viral 5'NCR region was
performed on blood and CSF pairs from 16 HAND patients. PCR products were cloned,
sequenced and analysed to determine viral diversity in blood and CSF. HPgV-1
viral loads were determined in paired blood and CSF of 2 patients by digital
droplet PCR. Nested PCR was also performed on CSF samples from patients with
other brain disorders. RESULTS: Virus was detected in both blood and CSF in 3 of
16 HAND patients. Viral loads were very high in blood (8.81 and 10.56 log
copies/ml) and 4-5 logs lower in CSF (4.68 and 5.84 log copies/ml). Sequence
analysis of 5'NCR clones in blood and CSF showed limited variation. The dominant
viral variant (based on clonal sequence identity) in blood and CSF was usually
identical. HPgV-1 was detected in CSF from patients with other brain disorders at
a similar frequency (15% versus 18.75% in HAND patients). CONCLUSION: While
several studies have reported HPgV-1 detection in CSF of patients with brain
disease, this is the only study that has examined both blood and CSF compartments
simultaneously. Our findings show that virus in CSF always coincided with
viraemia and levels were 4-5 logs higher in blood. While a rare, but specific
brain tropism cannot be excluded, blood is the more probable source of virus in
HAND patients.
PMID- 28499139
TI - A novel form of perceptual attunement: Context-dependent perception of a native
contrast in 14-month-old infants.
AB - By the end of their first year of life, infants have become experts in
discriminating the sounds of their native language, while they have lost the
ability to discriminate non-native contrasts. This type of phonetic learning is
referred to as perceptual attunement. In the present study, we investigated the
emergence of a context-dependent form of perceptual attunement in infancy.
Indeed, some native contrasts are not discriminated in certain phonological
contexts by adults, due to the presence of a language-specific process that
neutralizes the contrasts in those contexts. We used a mismatch design and
recorded high-density Electroencephalography (EEG) in French-learning 14-month
olds. Our results show that similarly to French adults, infants fail to
discriminate a native voicing contrast (e.g., [f] vs. [v]) when it occurs in a
specific phonological context (e.g. [ofbe] vs. [ovbe], no mismatch response),
while they successfully detected it in other phonological contexts (e.g., [ofne]
vs. [ovne], mismatch response). The present results demonstrate for the first
time that by the age of 14 months, infants' phonetic learning does not only rely
on the processing of individual sounds, but also takes into account in a language
specific manner the phonological contexts in which these sounds occur.
PMID- 28499140
TI - Is vehicle automation enough to prevent crashes? Role of traffic operations in
automated driving environments for traffic safety.
AB - Automated driving systems (ADSs) are expected to prevent traffic accidents caused
by driver carelessness on freeways. There is no doubt regarding this safety
benefit if all vehicles in the transportation system were equipped with ADSs;
however, it is implausible to expect that ADSs will reach 100% market penetration
rate (MPR) in the near future. Therefore, the following question arises: 'Can
ADSs, which consider only situations in the vicinity of an equipped vehicle,
really contribute to a significant reduction in traffic accidents?' To address
this issue, the interactions between equipped and unequipped vehicles must be
investigated, which is the purpose of this study. This study evaluated traffic
safety at different MPRs based on a proposed index to represent the overall rear
end crash risk of the traffic stream. Two approaches were evaluated for adjusting
longitudinal vehicle maneuvers: vehicle safety-based maneuvering (VSM), which
considers the crash risk of an equipped vehicle and its neighboring vehicles, and
traffic safety-based maneuvering (TSM), which considers the overall crash risk in
the traffic stream. TSM assumes that traffic operational agencies are able to
monitor all the vehicles and to intervene in vehicle maneuvering. An optimization
process, which attempts to obtain vehicle maneuvering control parameters to
minimize the overall crash risk, is integrated into the proposed evaluation
framework. The main purpose of employing the optimization process for vehicle
maneuvering in this study is to identify opportunities to improve traffic safety
through effective traffic management rather than developing a vehicle control
algorithm that can be implemented in practice. The microscopic traffic simulator
VISSIM was used to simulate the freeway traffic stream and to conduct systematic
evaluations based on the proposed methodology. Both TSM and VSM achieved
significant reductions in the potential for rear-end crashes. However, TSM
obtained much greater reductions when the MPR was greater than 50%. This study
should inspire transportation researchers and engineers to develop effective
traffic operations strategies for automated driving environments.
PMID- 28499141
TI - Can vehicle longitudinal jerk be used to identify aggressive drivers? An
examination using naturalistic driving data.
AB - This paper investigated the characteristics of vehicle longitudinal jerk (change
rate of acceleration with respect to time) by using vehicle sensor data from an
existing naturalistic driving study. The main objective was to examine whether
vehicle jerk contains useful information that could be potentially used to
identify aggressive drivers. Initial investigation showed that there are unique
characteristics of vehicle jerk in drivers' gas and brake pedal operations. Thus
two jerk-based metrics were examined: (1) driver's frequency of using large
positive jerk when pressing the gas pedal, and (2) driver's frequency of using
large negative jerk when pressing the brake pedal. To validate the performance of
the two metrics, drivers were firstly divided into an aggressive group and a
normal group using three classification methods (1) traveling at excessive speed
(speeding), (2) following too closely to a front vehicle (tailgating), and (3)
their association with crashes or near-crashes in the dataset. The results show
that those aggressive drivers defined using any of the three methods above were
associated with significantly higher values of the two jerk-based metrics.
Between the two metrics the frequency of using large negative jerk seems to have
better performance in identifying aggressive drivers. A sensitivity analysis
shows the findings were largely consistent with varying parameters in the
analysis. The potential applications of this work include developing quantitative
surrogate safety measures to identify aggressive drivers and aggressive driving,
which could be potentially used to, for example, provide real-time or post-ride
performance feedback to the drivers, or warn the surrounding drivers or vehicles
using the connected vehicle technologies.
PMID- 28499142
TI - Does mindfulness prepare adolescents for value-behavior concordance? Examining
the role of value content.
AB - Great thinkers throughout history advocated living one's values, yet little
research has examined factors that contribute to adolescents' value-behavior
concordance (VBC). Mindfulness may foster VBC via heightened awareness of values,
but VBC for intrinsic values may be more adaptive than VBC for extrinsic values.
To situate mindfulness in developmental context, we examined age and attachment
security as predictors of mindfulness. We collected self- and parent-report data
from 299 families (Mage-adolescents = 14.45, SD = 1.68; 51% female) from 42 US
states to test these ideas. Results indicated that mindfulness was positively
associated with intrinsic VBC but was negatively linked with extrinsic VBC, and
both kinds of VBC partially mediated the link from mindfulness to meaning (but
not life satisfaction). Attachment security was associated with higher
mindfulness. Overall, mindfulness may deliver its benefits by helping young
people avoid behaviors that align with extrinsic values.
PMID- 28499143
TI - Differences between clinician- and self-administered shoulder sustained
mobilization on scapular and shoulder muscle activity during shoulder abduction:
A repeated-measures study on asymptomatic individuals.
AB - BACKGROUND: Sustained glenohumeral postero-lateral glide administered by a
clinician is commonly used in the management of patients with shoulder pain. This
technique reduced shoulder muscle activity in asymptomatic individuals, but it is
unknown whether a self-administered version of the mobilization leads to similar
neuromuscular response. This study compared the effect of sustained shoulder
mobilizations (performed by a physiotherapist) with self-administered
mobilization (with a belt) on activity levels of scapular and glenohumeral
shoulder muscles. METHODS: Twenty-two individuals participated in this study,
which had a cross-over, repeated measures design. Seven shoulder muscles (upper
and lower trapezius, supraspinatus, infraspinatus, posterior deltoid, middle
deltoid, and serratus anterior) were monitored using surface electromyography
(SEMG) during shoulder abduction performed with a clinician-administered
sustained mobilization, and with self-administered sustained mobilization. Muscle
activity levels were measured prior, during and after the sustained glide was
applied to the shoulder. Mixed-effect models for repeated measures were used for
within- and between-condition comparisons. RESULTS: There was no carry-over
effect. Within-condition comparisons suggest that both interventions lead to
changes in scapular and shoulder muscle activity levels. No differences between
clinician-administered and self-administered mobilizations at intervention and
follow-up were found for the monitored muscles, with the exception of upper
trapezius. CONCLUSIONS: In young, asymptomatic individuals, self- or clinician
administered sustained mobilizations reduced activity levels of most scapular and
shoulder muscles during shoulder abduction. This effect was observed only while
the sustained glides were applied to the shoulder. At the immediate follow-up,
muscle activity levels were similar to baseline measurements.
PMID- 28499144
TI - Patterns of response to scrambled scenes reveal the importance of visual
properties in the organization of scene-selective cortex.
AB - Neuroimaging studies have found distinct patterns of neural response to different
categories of scene in scene-selective regions of the human brain. However, it is
not clear how information about scene category is represented in these regions.
Images from different categories vary systematically in their visual properties
as well as their semantic category. So, it is possible that patterns of neural
response could reflect variation in visual properties. To address this question,
we used fMRI to measure patterns of neural response to intact and scrambled scene
categories. Although scrambling preserved many of their visual characteristics,
perception of scene categories was severely impaired. Nevertheless, we found
distinct patterns of response to different scene categories in the
parahippocampal place area (PPA) and the occipital place area (OPA) for both
intact and scrambled scenes. Moreover, intact and scrambled scenes produced
highly similar patterns of response. Our finding that reliable and distinct
patterns of response in scene-selective regions are still evident when
categorical perception is impaired suggests that visual properties play an
important role in the topographic organization of these regions.
PMID- 28499145
TI - Human dorsomedial parieto-motor circuit specifies grasp during the planning of
goal-directed hand actions.
AB - According to one influential view, two specialized parieto-frontal circuits
control prehension: a dorsomedial stream for hand transport during reaching and a
dorsolateral stream for preshaping the fingers during grasping. However, recent
evidence argues that an area within the dorsomedial stream-macaque area V6A and,
its putative human homolog, superior parietal occipital cortex (SPOC) - encodes
both hand transport and grip formation. We tested whether planning varied hand
actions modulates functional connectivity between left SPOC and ipsilateral
primary motor cortex (M1) using a dual-site, paired-pulse transcranial magnetic
stimulation paradigm with two coils (dsTMS). Participants performed three
different hand actions to a target object comprising a small cylinder atop a
larger cylinder. These actions were: reaching-to-grasp the top (GT) using a
precision grip, reaching-to-grasp the bottom (GB) using a whole-hand grip, or
reaching-to-touch (Touch) the side of the target object without forming a grip.
Motor-evoked potentials (MEPs) from TMS to M1, with or without preceding TMS to
SPOC, were recorded from first dorsal interosseous (FDI) and abductor digiti
minimi (ADM) hand muscles in two experiments that varied timing parameters (the
stimulus onset asynchrony, SOA, between the 'GO' cue and stimulation and
interpulse interval, IPI, between SPOC and M1 stimulation). We found that
preparatory response amplitudes in the SPOC-M1 circuit of different hand muscles
were selectively modulated early in the motor plan for different types of grasps.
First, based on SPOC-M1 interactions, across two experiments, the role of the ADM
was facilitated during a whole-hand grasp of a large object (GB) relative to
other conditions under certain timing parameters (SOA = 150 msec; IPI = 6 msec).
Second, the role of the FDI was facilitated during hand action planning compared
to rest. These findings suggest that the human dorsomedial parieto-motor stream
plays a causal role in planning grip formation for object-directed actions.
PMID- 28499146
TI - RNA sequencing reveals pronounced changes in the noncoding transcriptome of aging
synaptosomes.
AB - Normal aging is associated with impairments in cognitive functions. These
alterations are caused by diminutive changes in the biology of synapses, and
ineffective neurotransmission, rather than loss of neurons. Hitherto, only a few
studies, exploring molecular mechanisms of healthy brain aging in higher
vertebrates, utilized synaptosomal fractions to survey local changes in aging
related transcriptome dynamics. Here we present, for the first time, a
comparative analysis of the synaptosomes transcriptome in the aging mouse brain
using RNA sequencing. Our results show changes in the expression of genes
contributing to biological pathways related to neurite guidance, synaptosomal
physiology, and RNA splicing. More intriguingly, we also discovered alterations
in the expression of thousands of novel, unannotated lincRNAs during aging.
Further, detailed characterization of the cleavage and polyadenylation factor I
subunit 1 (Clp1) mRNA and protein expression indicates its increased expression
in neuronal processes of hippocampal stratum radiatum in aging mice. Together,
our study uncovers a new layer of transcriptional regulation which is targeted by
aging within the local environment of interconnecting neuronal cells.
PMID- 28499147
TI - Fructose increases corticosterone production in association with NADPH metabolism
alterations in rat epididymal white adipose tissue.
AB - Metabolic syndrome is an array of closely metabolic disorders that includes
glucose intolerance/insulin resistance, central obesity, dyslipidemia, and
hypertension. Fructose, a highly lipogenic sugar, has profound metabolic effects
in adipose tissue, and has been associated with the etiopathology of many
components of the metabolic syndrome. In adipocytes, the enzyme 11 beta-HSD1
amplifies local glucocorticoid production, being a key player in the pathogenesis
of central obesity and metabolic syndrome. 11 beta-HSD1 reductase activity is
dependent on NADPH, a cofactor generated by H6PD inside the endoplasmic
reticulum. Our focus was to explore the effect of fructose overload on epididymal
white adipose tissue (EWAT) machinery involved in glucocorticoid production and
NADPH and oxidants metabolism. Male Sprague-Dawley rats fed with a fructose
solution (10% (w/v) in tap water) during 9 weeks developed some characteristic
features of metabolic syndrome, such as hypertriglyceridemia, and hypertension.
In addition, high levels of plasma and EWAT corticosterone were detected.
Activities and expressions of H6PD and 11 beta-HSD1, NAPDH content, superoxide
anion production, expression of NADPH oxidase 2 subunits, and indicators of
oxidative metabolism were measured. Fructose overloaded rats showed an increased
potential in oxidant production respect to control rats. In parallel, in EWAT
from fructose overloaded rats we found higher expression/activity of H6PD and 11
beta-HSD1, and NADPH/NADP+ ratio. Our in vivo results support that fructose
overload installs in EWAT conditions favoring glucocorticoid production through
higher H6PD expression/activity supplying NADPH for enhanced 11 beta-HSD1
expression/activity, becoming this tissue a potential extra-adrenal source of
corticosterone under these experimental conditions.
PMID- 28499149
TI - Home as a place of caring and wellbeing? A qualitative study of informal carers
and caring networks lived experiences of providing in-home end-of-life care.
AB - Although the burden of caring is well described, the value of home as a potential
place of wellbeing and support for informal caring networks when providing end-of
life care is not well recognised. Interviews and focus groups with 127 primary
carers and members of informal care networks revealed their collaborative stories
about caring for a dying person at home. Four themes emerged from the data: home
as a place of comfort and belonging; places of social connection and
collaborative caring; places of connection to nature and the non-human; places of
achievement and triumph. When support is available, nurturing carer wellbeing may
be best achieved at home.
PMID- 28499148
TI - Long-term neighborhood poverty trajectories and obesity in a sample of california
mothers.
AB - Neighborhoods (and people) are not static, and are instead shaped by dynamic long
term processes of change (and mobility). Using the Geographic Research on
Wellbeing survey, a population-based sample of 2339 Californian mothers, we
characterize then investigate how long-term latent neighborhood poverty
trajectories predict the likelihood of obesity, taking into account short-term
individual residential mobility. We find that, net of individual and neighborhood
level controls, living in or moving to tracts that experienced long-term low
poverty was associated with lower odds of being obese relative to living in
tracts characterized by long-term high poverty.
PMID- 28499150
TI - Effect of yarn structure on wicking and its impact on bloodstain pattern analysis
(BPA) on woven cotton fabrics.
AB - Bloodstain pattern analysis (BPA) of bloodstains on hard, non-porous surfaces has
found widespread use in crime scene analysis and reconstruction for violent
crimes in which bloodshed occurs. At many violent crime scenes, bloody clothing
is also found and may be analyzed. However, to date, there are no definitive
methods for analyzing bloodstains on textiles, even for simple drip stains. There
are two major classes of textiles used for apparel and household textiles, weaves
and knits. In this article, drip stains on two 100% cotton plain weave fabrics
representative of bed sheets are analyzed. Since it is common practice in the
manufacture of bed sheeting to use different types of yarn in the warp and weft
direction to reduce cost, custom weaves were made from yarns produced by each of
the three most common staple yarn production techniques to control this variable.
It was found that porcine blood wicked into the fabrics made with ring spun yarn,
but not into those made with open end or vortex spun yarns. The uneven wicking of
blood into the different yarns resulted in elliptical-shaped stains on commercial
bed sheeting that can be misleading when performing bloodstain pattern
interpretation based on the stain morphology. This surprising result demonstrates
that it is not sufficient to analyze the structure of the fabric, but one must
also characterize the yarns from which the fabric is made. This study highlights
the importance of a deeper characterization of the textile structure, even down
to the yarn level, for BPA on textiles.
PMID- 28499151
TI - Biphenyl based stationary phases for improved selectivity in complex steroid
assays.
AB - The measurement of steroid hormones and their corticoid precursors is an
important aspect in endocrinology since these analytes are biomarkers for several
endocrine disorders. Over the last few years, HPLC-MS/MS has become the method of
choice to analyze these compounds. There are already several methods using
stationary phases modified with C18 groups. However, since these columns
sometimes do not enable sufficient separation of some isobaric steroids, we
investigated the potential of a different RP modification using biphenyl groups
for the separation of challenging isobars such as corticosterone, 11- and 21
deoxycortisol. The aim of our work was the development of an isotope dilution
UHPLC-MS/MS assay for clinical research that combines simple and effective sample
preparation with a powerful MS method quantifying a broad steroid panel
(aldosterone, corticosterone, cortisol, cortisone, 11-deoxycorticosterone, 11
deoxycortisol, 21-deoxycortisol, dehydroepiandrosterone, dehydroepiandrosterone
sulfate, 17-OH-progesterone, progesterone, and testosterone) in human serum.
After a manual protein precipitation step using zinc trifluoroacetate (ZnTFA) in
methanol, the supernatants were directly injected into the UHPLC-MS system.
Chromatographic baseline separation of all isobaric compounds (corticosterone<
>11-deoxycortisol<->21-deoxycortisol, 17-OH-progesterone<->11
deoxycorticosterone, and aldosterone<->cortisone) was achieved using a Kinetex
Biphenyl column (150*2.1mm, 1.7MUm) with a mobile phase consisting of 0.2mM
ammonium fluoride in water and methanol. The total run time was 10min. For
detection we used a Xevo TQ-S mass spectrometer operating in the ESI positive and
negative modes. The method was validated according to the EMA guideline for
bioanalytical method validation. The results for accuracy (within-run: 92.3%
115%, between-run: 92.4 %-113%) and imprecision (within-run: 0.80%-9.05%, between
run: 1.98 %-15.2%) were satisfying. The recovery ranged from 95% to 111%. The
matrix effect was between 93% and 112% and an excellent linearity with R2>0.99
for all analytes was achieved. It was demonstrated that biphenyl based columns
are a powerful tool for comprehensive, MS based steroid assays including various
isobaric substances. Additionally, we could evince that ZnTFA is a convenient
precipitation agent suitable for steroid analysis.
PMID- 28499152
TI - Development of assay for determination of eletriptan hydrobromide in loaded PLGA
nanoparticles.
AB - Eletriptan Hydrobromide is a serotonin 5-HT1 receptor agonist and it used for the
treatment of migraine headaches with or without aura. Even if the drug is well
absorbed after oral administration, it has some drawbacks like first pass
metabolism and decrease in bioavailability after migraine attacks. Encapsulation
of drug into polymeric nanoparticles is one of the methods for protecting the
drug against degradation. The present work described a preparation of Eletriptan
Hydrobromide loaded poly (d,l-lactide-co-glycolide) nanoparticles prepared using
o/w single emulsion solvent evaporation method. In order to determine the factors
affecting the physicochemical properties of the nanoparticles on the particle
size of poly (d,l-lactide-co-glycolide) nanoparticles, D-Optimal design is used.
Moreover, novel, simple, sensitive, selective, and fully validated
chromatographic technique for the quantification of Eletriptan Hydrobromide from
Eletriptan Hydrobromide loaded poly(d,l-lactide-co-glycolide) nanoparticles was
developed. Poly(d,l-lactide-co-glycolide) concentration, sonication time and
sonication energy were found as significant factors (p<0.05) on particle size of
nanoparticles. Limit of detection and limit of quantification values were
calculated as 0.28MUgmL-1and 0.86MUgmL-1, respectively.
PMID- 28499153
TI - Safety and efficacy of warfarin in patients with moderate thrombocytopenia.
AB - INTRODUCTION: Patients with moderate thrombocytopenia and comorbidities requiring
anticoagulation are currently sub-optimally treated because of bleeding concerns.
Guidance on anticoagulating such patients is currently lacking because of limited
data on safety and efficacy of anticoagulation in such patients. METHODS: This
retrospective study compared the incidence of bleeding and thrombosis in a cohort
of warfarinized patients with sustained platelet counts below 100*109/L against a
cohort with normal platelet counts (>140*109/L). Primary outcomes of safety and
efficacy were determined by incidence rate ratios (IRR) of bleeding and
thrombotic events. International normalized ratio (INR) and platelet counts
during adverse events in thrombocytopenic arm were secondary outcomes. RESULTS:
137 thrombocytopenic patients (104,985 patient-exposure days) were compared
against 939 normal patients (715,193 patient-exposure days). IRR of minor, major
bleeding and thrombosis among thrombocytopenic patients were 3.03 (95% CI: 1.57
5.60), 1.48 (95% CI: 0.44-3.98), and 0.807 (95% CI: 0.09-3.43) respectively.
Median INR and platelet count readings during minor and major bleeds were 3.60
(IQR: 2.70-4.12) and 3.12 (IQR: 2.82-4.22), and 99*109/L (IQR: 77.0-147.0*109/L)
and 115*109/L (IQR: 107.5-169.5*109/L) respectively. CONCLUSION: Warfarinized
thrombocytopenic patients are at higher risk of minor bleeding complications with
a higher tendency for major bleeding but derive similar benefits against
thrombotic events compared to normal patients. Bleeding events are associated
with higher INRs. A narrow INR target with an upper limit below 2.5 together with
closer anticoagulation monitoring may improve safety of patients.
PMID- 28499154
TI - Mutation of the Kunitz-type proteinase inhibitor domain in the amyloid beta
protein precursor abolishes its anti-thrombotic properties in vivo.
AB - INTRODUCTION: Kunitz proteinase inhibitor (KPI) domain-containing forms of the
amyloid beta-protein precursor (AbetaPP) inhibit cerebral thrombosis. KPI domain
lacking forms of AbetaPP are abundant in brain. Regions of AbetaPP other than the
KPI domain may also be involved with regulating cerebral thrombosis. To determine
the contribution of the KPI domain to the overall function of AbetaPP in
regulating cerebral thrombosis we generated a reactive center mutant that was
devoid of anti-thrombotic activity and studied its anti-thrombotic function in
vitro and in vivo. METHODS: To determine the extent of KPI function of AbetaPP in
regulating cerebral thrombosis we generated a recombinant reactive center KPIR13I
mutant devoid of anti-thrombotic activity. The anti-proteolytic and anti
coagulant properties of wild-type and R13I mutant KPI were investigated in vitro.
Cerebral thrombosis of wild-type, AbetaPP knock out and AbetaPP/KPIR13I mutant
mice was evaluated in experimental models of carotid artery thrombosis and
intracerebral hemorrhage. RESULTS: Recombinant mutant KPIR13I domain was
ineffective in the inhibition of pro-thrombotic proteinases and did not inhibit
the clotting of plasma in vitro. AbetaPP/KPIR13I mutant mice were similarly
deficient as AbetaPP knock out mice in regulating cerebral thrombosis in
experimental models of carotid artery thrombosis and intracerebral hemorrhage.
CONCLUSIONS: We demonstrate that the anti-thrombotic function of AbetaPP
primarily resides in the KPI activity of the protein.
PMID- 28499155
TI - Simple screening protocol for identification of potential mycoremediation tools
for the elimination of polycyclic aromatic hydrocarbons and phenols from
hyperalkalophile industrial effluents.
AB - A number of fungal strains belonging to the ascomycota, basidiomycota and
zygomycota genera were subjected to an in vitro screening regime to assess their
ligninolytic activity potential, with a view to their potential use in
mycoremediation-based strategies to remove phenolic compounds and polycyclic
aromatic hydrocarbons (PAHs) from industrial wastewaters. All six basidiomycetes
completely decolorized remazol brilliant blue R (RBBR), while also testing
positive in both the guaiacol and gallic acid tests indicating good levels of
lignolytic activity. All the fungi were capable of tolerating phenanthrene, benzo
alpha- pyrene, phenol and p-chlorophenol in agar medium at levels of 10 ppm. Six
of the fungal strains, Pseudogymnoascus sp., Aspergillus caesiellus, Trametes
hirsuta IBB 450, Phanerochate chrysosporium ATCC 787, Pleurotus ostreatus MTCC
1804 and Cadophora sp. produced both laccase and Mn peroxidase activity in the
ranges of 200-560 U/L and 6-152 U/L, respectively, in liquid media under nitrogen
limiting conditions. The levels of adsorption of the phenolic and PAHs were
negligible with 99% biodegradation being observed in the case of benzo-alpha
pyrene, phenol and p-chlorophenol. The aforementioned six fungal strains were
also found to be able to effectively treat highly alkaline industrial wastewater
(pH 12.4). When this wastewater was supplemented with 0.1 mM glucose, all of the
tested fungi, apart from A. caesiellus, displayed the capacity to remove both the
phenolic and PAH compounds. Based on their biodegradative capacity we found T.
hirsuta IBB 450 and Pseudogymnoascus sp., to have the greatest potential for
further use in mycoremediation based strategies to treat wastestreams containing
phenolics and PAHs.
PMID- 28499156
TI - Treatment of chemical cleaning wastewater and cost optimization by response
surface methodology coupled nonlinear programming.
AB - The real alkaline cleaning wastewater (ACW) was treated by a process consisting
of neutralization, NaClO oxidation and aluminum sulfate (AS) coagulation, and a
novel response surface methodology coupled nonlinear programming (RSM-NLP)
approach was developed and used to optimize the oxidation-coagulation process
under constraints of relevant discharge standards. Sulfuric acid neutralization
effectively removed chemical oxygen demand (COD), surfactant alkylphenol
ethoxylates (OP-10) and silicate at the optimum pH of 7.0, with efficiencies of
62.3%, >82.7% and 94.2%, respectively. Coagulation and adsorption by colloidal
hydrated silica formed during neutralization were the major removal mechanisms.
NaClO oxidation achieved almost complete removal of COD, but was ineffective for
the removal of surfactant OP-10. AS coagulation followed by oxidation can
efficiently remove OP-10 with the formation of Si-O-Al compounds. The optimum
conditions for COD <=100 mg/L were obtained at hypochlorite to COD molar ratio of
2.25, pH of 10.0 and AS dosage of 0.65 g Al/L, with minimum cost of 9.58 $/m3
ACW. This study shows that the integrative RSM-NLP approach could effectively
optimize the oxidation-coagulation process, and is attractive for techno-economic
optimization of systems with multiple factors and threshold requirements for
response variables.
PMID- 28499157
TI - Identify temporal trend of air temperature and its impact on forest stream flow
in Lower Mississippi River Alluvial Valley using wavelet analysis.
AB - Characterization of stream flow is essential to water resource management, water
supply planning, environmental protection, and ecological restoration; while air
temperature variation due to climate change can exacerbate stream flow and add
instability to the flow. In this study, the wavelet analysis technique was
employed to identify temporal trend of air temperature and its impact upon forest
stream flows in Lower Mississippi River Alluvial Valley (LMRAV). Four surface
water monitoring stations, which locate near the headwater areas with very few
land use disturbances and the long-term data records (60-90 years) in the LMRAV,
were selected to obtain stream discharge and air temperature data. The wavelet
analysis showed that air temperature had an increasing temporal trend around its
mean value during the past several decades in the LMRAV, whereas stream flow had
a decreasing temporal trend around its average value at the same time period in
the same region. Results of this study demonstrated that the climate in the LMRAV
did get warmer as time elapsed and the streams were drier as a result of warmer
air temperature. This study further revealed that the best way to estimate the
temporal trends of air temperature and stream flow was to perform the wavelet
transformation around their mean values.
PMID- 28499158
TI - Multi-segmental movement patterns reflect juggling complexity and skill level.
AB - The juggling action of six experts and six intermediates jugglers was recorded
with a motion capture system and decomposed into its fundamental components
through Principal Component Analysis. The aim was to quantify trends in movement
dimensionality, multi-segmental patterns and rhythmicity as a function of
proficiency level and task complexity. Dimensionality was quantified in terms of
Residual Variance, while the Relative Amplitude was introduced to account for
individual differences in movement components. We observed that: experience
related modifications in multi-segmental actions exist, such as the progressive
reduction of error-correction movements, especially in complex task condition.
The systematic identification of motor patterns sensitive to the acquisition of
specific experience could accelerate the learning process.
PMID- 28499159
TI - Sensitivity of biomechanical outcomes to independent variations of hindfoot and
forefoot stiffness in foot prostheses.
AB - Many studies have reported the effects of different foot prostheses on gait, but
most results cannot be generalized because the prostheses' properties are seldom
reported. We varied hindfoot and forefoot stiffness in an experimental foot
prosthesis, in increments of 15N/mm, and tested the parametric effects of these
variations on treadmill walking in unilateral transtibial amputees, at speeds
from 0.7 to 1.5m/s. We computed outcomes such as prosthesis energy return, center
of mass (COM) mechanics, ground reaction forces, and joint mechanics, and
computed their sensitivity to component stiffness. A stiffer hindfoot led to
reduced prosthesis energy return, increased ground reaction force (GRF) loading
rate, and greater stance-phase knee flexion and knee extensor moment. A stiffer
forefoot resulted in reduced prosthetic-side ankle push-off and COM push-off
work, and increased knee extension and knee flexor moment in late stance. The
sensitivity parameters obtained from these tests may be useful in clinical
prescription and further research into compensatory mechanisms of joint function.
PMID- 28499160
TI - Predicting settling performance of ANAMMOX granular sludge based on fractal
dimensions.
AB - The settling performance of ANAMMOX granular sludge determines the biomass
retention in reactors, and finally determines the potential reaction capacity. In
this paper, Stokes equation was modified by fractal dimensions to describe the
settling performance of ANAMMOX granular sludge. A new method was developed to
obtain fractal dimensions, and a fractal settling model was established for
ANAMMOX granular sludge. The fractal settling model was excellent with only a
small deviation of 0.8% from the experimental data. Assuming normal distribution
of all Feret diameters, 88% experimental data fell into the 90% confidence
interval of settling velocities. Further assuming logarithmic normal
distribution, 95% experimental data fell into the 90% confidence interval. The
fractal settling model is helpful for the prediction of settling velocities of
granular sludge and the optimization of bioreactor performance.
PMID- 28499161
TI - Determination of the Henry's law constants of low-volatility compounds via the
measured air-phase transfer coefficients.
AB - Accurate Henry's law constants (H) are unavailable for the majority of organic
pollutants, especially those having a low volatility. A novel kinetics-based
experimental method is introduced to determine H for a wide range of low-H
compounds. The method consists of measuring independently the water-to-air
transfer coefficient (KL) and the associated air-phase transfer coefficient (kG)
of a low-H chemical (solute) in water when KL ? kGH prevails according to the two
film theory. The kG for a solute is obtained via a developed gas-dynamic equation
that relates kG to the solute molecular weight and the solute-vapor escaping
efficiency (beta) through a boundary air layer. The value of beta is only a
function of the in situ air turbulence level, independent of the chemical
species. Thus, the required beta for solutes can be estimated from the
evaporative rates of pure volatile liquids under the same ambient setting. By
relating the estimated kG with the measured KL of a low-H solute, the solute H is
established. The H values of 45 low-H chemicals, including many complex
pesticides, in the range of ~10-7 to ~10-3 have thus been determined. The
accountability of the method is underscored by the consistency of the measured
and credible literature H values for a number of the low-H compounds studied.
PMID- 28499162
TI - Factors associated with medication adherence among patients with diabetes in the
Middle East and North Africa region: A systematic mixed studies review.
AB - Multiple systematic reviews were conducted investigating factors associated with
medication adherence worldwide. However, investigations from the Middle East and
North Africa (MENA) region were largely underrepresented in those reviews.
Therefore, the objective of this systematic review is to identify the factors
influencing medication adherence among patients with diabetes in the MENA region.
A systematic literature search was conducted through Cochrane Library, EBSCO,
EMBASE, Google Scholar, ISI Web of Science, PubMed, ScienceDirect, SCOPUS, and
ProQuest. Studies were included if they determined factors associated with
medication adherence among patients with diabetes within the MENA region. Quality
was assessed using Crow Critical Appraisal Tool. Thirty primary studies from 10
MENA countries were included. The factors associated with medication adherence
were categorized into demographics-related; disease- and medication-related;
perception, attitude and psychological feelings-related; and societal-related
factors. Positively associated factors included knowledge about the disease and
medications, regular follow-up visits, and patients' positive beliefs about
effectiveness and motivations about medications, while negatively associated
factors included forgetfulness, side effects, and polypharmacy. Factors
associated with medication adherence among patients with diabetes in the MENA
region are highly diverse. The identified factors can serve as potential targets
for culturally-relevant interventions to improve medication adherence and overall
health outcomes.
PMID- 28499163
TI - The Diabetic Retinopathy Barometer Study: Global perspectives on access to and
experiences of diabetic retinopathy screening and treatment.
AB - AIM: To assess the level of awareness, prevention and treatment of Diabetic Eye
Disease (DED) comprising Diabetic Retinopathy (DR) and Diabetic Macula Edema
(DME) retinopathy among adults with diabetes and health professionals. METHODS:
The Diabetic Retinopathy Barometer Study consisted of a qualitative study, which
consisted of semi-structured interviews, and a quantitative study using online
surveys for adults with diabetes and for health professionals. RESULTS: A total
of 4340 adults with diabetes and 2329 health professionals participated in the
surveys. Diabetic eye disease (DED) without macular edema (DME) was reported by
19.5% of adults with diabetes and a further 7.6% reported that they had DME.
Although 94% of adults with diabetes saw a health care professional for their
diabetes, only 79% had ever had an eye examination for DED, and 23% had not had
an eye examination in the last year. Moreover, 65% of the ophthalmologists
surveyed reported that most patients presented when visual problems had already
occurred. Overall, 62% of people with DED had received treatment. Of these, 74%
had laser therapy, 29% surgery and 24% anti-VEGF therapy. CONCLUSION: Strategic
investment is required to enhance patient education and professional training on
the importance of regular eye examinations; and in providing accessible DR
screening programmes and proactive treatments.
PMID- 28499164
TI - Mechanical properties and antibiotic release characteristics of poly(methyl
methacrylate)-based bone cement formulated with mesoporous silica nanoparticles.
AB - The influence of mesoporous silica nanoparticles (MSNs) loaded with antibiotics
on the mechanical properties of functional poly(methyl methacrylate)-(PMMA) based
bone cements is investigated. The incorporation of MSNs to the bone cements
(8.15wt%) shows no detrimental effects on the biomechanical properties of the
freshly solidified bone cements. Importantly, there are no significant changes in
the compression strength and bending modulus up to 6 months of aging in PBS
buffer solution. The preserved mechanical properties of MSN-functionalized bone
cements is attributed to the unchanged microstructures of the cements, as more
than 96% of MSNs remains in the bone cement matrix to support the cement
structures after 6 months of aging. In addition, the MSN-functionalized bone
cements are able to increase the drug release of gentamicin (GTMC) significantly
as compared with commercially available antibiotic-loaded bone cements. It can be
attributed to the loaded nano-sized MSNs with uniform pore channels which build
up an effective nano-network path enable the diffusion and extended release of
GTMC. The combination of excellent mechanical properties and sustainable drug
delivery efficiency demonstrates the potential applicability of MSN
functionalized PMMA bone cements for orthopedic surgery to prevent post-surgery
infection.
PMID- 28499165
TI - Preparing diopside nanoparticle scaffolds via space holder method: Simulation of
the compressive strength and porosity.
AB - In the present study, diopside nanopowders were prepared via mechanical milling
with eggshell as the calcium source. The space holder method (compaction of
ceramic powder and spacer) as one of the most important methods to produce
ceramic/metal scaffolds was used to produce diopside scaffolds. For the first
time, the effect of the spacer size on mechanical properties and porosity of the
obtained scaffolds was experimentally discussed. According to the results
obtained, the NaCl particles (as the spacer) with the size of 400-600um
maintained their original spherical shape during the compaction and sintering
processes. As a new work, the most important parameters including the spacer
type, spacer concentration, spacer size, and applied pressure were considered,
and their effects on mechanical properties and porosity of diopside scaffolds
were simulated. Gene Expression Programming (GEP), as one of the most branches of
the artificial intelligence, was used for simulation process. By using the GEP,
two equations were introduced to predict the compressive strength and porosity of
the obtained scaffolds with the lowest error values. The 3D diagrams extracted
from the model were used to evaluate the combined effect of the process
parameters on the compressive strength and porosity of the scaffolds. The GEP
model presented in this work has a very low level of error and a high level of
the squared regression for predicting the compressive strength and porosity of
diopside scaffolds.
PMID- 28499166
TI - Potential biodegradable Zn-Cu binary alloys developed for cardiovascular implant
applications.
AB - Binary Zn-Cu alloy system is developed as potential biodegradable materials for
cardiovascular implant application. The microstructure, tensile properties, in
vitro corrosion behavior, cytotoxicity and antibacterial property of as-extruded
Zn-xCu (x=1, 2, 3, and 4wt%) alloys are investigated systematically. It shows
that as Cu content increases more CuZn5 phase precipitates. After extrusion, the
CuZn5 phases are broken and the grains of Zn-xCu alloys are refined. Tensile test
shows that Cu addition could significantly improve the mechanical properties of
Zn-xCu alloys. Particularly, the elongation of the Zn-4Cu reaches 50.6+/-2.8%,
which could facilitate the micro-tubes processing for stent fabrication. The
micro-tubes of 3mm in outer diameter and 0.2mm in thickness as well as vascular
stents have been fabricated successfully using the Zn-Cu binary alloy. The
degradation rates of Zn-xCu alloys in c-SBF solution are quite low, which vary
from 22.1+/-4.7 to 33.0+/-1.0MUmyear-1. With increasing Cu concentration, the
corrosion rates of the Zn-xCu alloys generally exhibit a little increase compared
with pure Zn, which show no significant difference among Zn-xCu alloys. In vitro
test shows that Zn-xCu alloys exhibit acceptable cytotoxicity to human
endothelial cells and the antibacterial property (S. aureus) is perfect when Cu
concentration is higher than 2wt%. Therefore, the newly developed Zn-xCu binary
alloys could be promising candidates for biodegradable cardiovascular implant
application due to their excellent combination of strength and ductility, low
degradation rates, acceptable cytotoxicity and good antibacterial property.
PMID- 28499167
TI - Electrochemical behavior of hemin binding with human centrin 3.
AB - The electrochemical responses of human centrin 3 (HsCen3) binding with hemin were
studied by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) using
glassy carbon electrodes (GCEs). In CV, the formal potential (E0') of hemin with
the addition of HsCen3 shifted from -0.51 to -0.36V (versus saturated calomel
electrode, SCE), indicating that a new species of hemin-HsCen3 had formed. Upon
binding with HsCen3, the redox current of hemin in CV and DPV decreased
significantly. Based on their titration curves, the association constant of
HsCen3 with hemin was obtained with a logK of approximately 4, which was
consistent with that obtained from spectroscopy. Combining UV-Vis, fluorescence
emission, and electrochemical methods, His100 located on the alpha-helix between
the two domains of HsCen3 was identified as the ligand binding residue of hemin.
The protein binding-induced change in electrochemical signal was thus used to
construct the diffusion coefficient (D=1.43*10-7cm2/s), the charge-transfer
coefficient (alpha=0.49), and electron transfer standard rate constant
(ks=2.54*10-2s-1) in the presence or absence of HsCen3. The electrochemical
investigation of hemin bound with HsCen3 may provide useful data for
understanding the biological processes of calcium-binding protein.
PMID- 28499168
TI - Novel Imidazo[4,5-c][1,2,6]thiadiazine 2,2-dioxides as antiproliferative
trypanosoma cruzi drugs: Computational screening from neural network, synthesis
and in vivo biological properties.
AB - A new family of imidazo[4,5-c][1,2,6]thiadiazine 2,2-dioxide with
antiproliferative Trypanosoma cruzi properties was identified from a neural
network model published by our group. The synthesis and evaluation of this new
class of trypanocidal agents are described. These compounds inhibit the growth of
Trypanosoma cruzi, comparable with benznidazole or nifurtimox. In vitro assays
were performed to study their effects on the growth of the epimastigote form of
the Tulahuen 2 strain, as well as the epimastigote and amastigote forms of CL
clone B5 of Trypanosoma cruzi. To verify selectivity towards parasite cells, the
non-specific cytotoxicity of the most relevant compounds was studied in mammalian
cells, i.e. J774 murine macrophages and NCTC clone 929 fibroblasts. Furthermore,
these compounds were assayed regarding the inhibition of cruzipain. In vivo
studies revealed that one of the compounds, 19, showed interesting trypanocidal
activity, and could be a very promising candidate for the treatment of Chagas
disease.
PMID- 28499170
TI - 4-Phenyl quinoline derivatives as potential serotonin receptor ligands with
antiproliferative activity.
AB - Antagonists of signaling receptors are often effective non-toxic therapeutic
agents. Over the years, there have been evidences describing the role of
serotonin or 5-hydroxytryptamine (5-HT) in development of cancer. Although there
are reports on the antiproliferative effects of some serotonin receptor
antagonists, there are very few investigations related to understanding their
structure-activity relationships. In this study, we report the screening of a
library of 4-phenyl quinoline derivatives for their antiproliferative activities.
Preliminary docking studies indicated that these ligands had the ability to bind
to two of the serotonin receptors, 5-HT1B and 5-HT2B. The results of the in
silico experiments were validated by performing in vitro studies on MCF-7 breast
cancer cell line. The ethylpiperazine derivatives showed maximum toxicity against
this cancer cell line. The compounds inhibited Calcium ion efflux (induced by
serotonin) and ERK activation. One of the most active 4-phenyl quinoline
derivatives (H3a) also induced apoptosis, thereby, suggesting the use of this
scaffold as a potential anticancer drug.
PMID- 28499169
TI - Two novel dinuclear ellipsoid Ni(II) and Co(II) complexes bridged by 4,5
bis(pyrazol-1-yl)phthalic acid: Synthesis, structural characterization and
biological evaluation.
AB - Two novel complexes, [Ni2(L)2(H2O)3].4(H2O) (1) and [Co2(L)2(H2O)3].5(H2O) (2)
[H2L = 4,5-bis(pyrazol-1-yl) phthalic acid] were synthesized and characterized by
spectroscopy (IR, 1H NMR), and elemental analysis. The structures for the
complexes were determined by X-ray crystallography providing the dinuclear
ellipsoid Ni(II) and Co(II) complexes bridged by 4,5-bis(pyrazol-1-yl)phthalic
acid ligands with same coordination modes. The interaction capacity of the
complexes with FS-DNA (fish sperm DNA) has been investigated by UV and
fluorescence spectroscopy. Gel electrophoresis assay demonstrated the ability of
the complexes to cleave the pBR322 plasmid DNA. The cytotoxic activity of the
complexes was tested against two different cancer cell lines, HeLa (human cervix
epithelia carcinoma cells) and KB (human oral epithelial carcinoma cells),
exhibiting significant cancer cell inhibitory rate. Furthermore, flow cytometry
experiments and morphological apoptosis studies showed that the complexes induced
apoptosis of KB tumor cell lines. The good visualization images supported with
the experimental results of structure-activity relationship.
PMID- 28499171
TI - Quinazoline based alpha1-adrenoreceptor antagonists with potent antiproliferative
activity in human prostate cancer cell lines.
AB - New alpha1-adrenoreceptor (alpha1-AR) antagonists related to prazosin and
doxazosin were synthesized by replacing piperazine ring with (S)- or (R)-3
aminopiperidine. Binding studies indicated that the S configuration at the 3-C
position of the piperidine ring is crucial for an optimal interaction of the
compounds at all three alpha1-AR subtypes. Quinazolines 9 and 10, bearing a
quinone ring on the lateral chain, exhibited also potent antiproliferative
activity in LNCaP androgen-sensitive prostate cancer cell lines, higher than that
of doxazosin. Compound 10 increased apoptosis, in terms of DNA fragmentation,
without triggering cell necrosis. The prooxidant activity found in compound 10
may underlie its ability to inhibit cell proliferation in synergy with the effect
mediated by alpha1-AR antagonism. Due to its better biological profile compared
to doxazosin for LNCaP cell line, compound 10 might be a valuable lead compound
for the design of new prostate antitumor agents.
PMID- 28499172
TI - Fluorescence quenching study on the interaction of ferroferric oxide
nanoparticles with bovine serum albumin.
AB - Fluorescence quenching was used to study the potential interaction mechanism of
Bovine serum albumin (BSA) with either hydrophilic ferroferric oxide (Fe3O4)
nanoparticles (NPs) or hydrophobic Fe3O4 NPs. The experimental results indicated
the mechanism between BSA and hydrophilic Fe3O4 NPs was static quenching and the
one between BSA and hydrophobic Fe3O4 NPs was dynamic process that was drove by
Forster's resonance energy transfer (FRET). And the binding parameters for the
interaction of BSA with either hydrophilic or hydrophobic Fe3O4 NPs were
calculated by using the fluorescence quenching measurement. The binding constant
(KA) values of hydrophilic Fe3O4 NPs were 8518.73+/-23.35 (at 298K), 1190.31+/
15.41 (at 306K) and 321.97+/-8.57 (at 313K), respectively. The thermodynamic
analysis implied that the intermolecular forces between BSA and hydrophilic Fe3O4
NPs were Van der Waals interaction or hydrogen bond, because the values of DeltaH
and DeltaS between them were negative. While the one of BSA and hydrophobic Fe3O4
NPs involved hydrophobic forces, owing to the positive DeltaH and DeltaS between
them. But they were all enthalpy-driven and exothermic, since their DeltaG values
were all negative. Synchronous fluorescence spectroscopy suggested that the
conformation of tryptophan residue of BSA was changed in the presence of
hydrophilic Fe3O4 NPs or hydrophobic Fe3O4 NPs, because the position of the
maximum emission wavelength had a discernible red shift.
PMID- 28499173
TI - Combination photodynamic therapy of human breast cancer using salicylic acid and
methylene blue.
AB - The objective of this study was to evaluate the effects of combination therapy
with methylene blue (MB) assisted photodynamic therapy (PDT) and salicylic acid
(SA) as chemo-therapy anticancer agent. The binding of salicylic acid to
methylene blue was studied using spectrophotometric method. The results show the
1:2 complex formation between SA and MB. The binding constants and related Gibbs
free energies o are obtained (Kb1=183.74, Kb2=38.13 and ?Gb1 degrees =12.92kJ.mol
1, ?Gb2 degrees =9.02kJ.mol-1). The spectrophotometric results show the
improvement in solubilization and reduction prevention for SA and MB in the
complex form. These results are in agreements with cellular experiments. The dark
toxicity measurements represent the improve efficacy of chemotherapy using
combination of SA and MB. The photodynamic therapy results (using red LED as
light source (630nm; power density: 30mWcm-2)) show that the cancer cell killing
efficiency of MB increases in the combination with SA due to reduction prevention
and stabilization of monomeric form of MB.
PMID- 28499174
TI - Interaction between triethanolamine and singlet or triplet excited state of
xanthene dyes in aqueous solution.
AB - Triethanolamine (TEOA) has been often used as a hole-scavenger in dye-sensitized
semiconductor photocatalytic systems. However, the femtosecond time-resolved
kinetics of the interaction between a sensitized dye and TEOA has not been
reported in literatures. Herein, we selected four commonly used xanthene dyes,
such as fluorescein, dibromofluorescein, eosin Y, and erythrosine B, and studied
their ultrafast fluorescence quenching dynamics in the presence of TEOA in
aqueous solution, respectively, by using both femtosecond transient absorption
and time-resolved fluorescence measurements. We obtained the electron transfer
rate from TEOA to each photoexcited xanthene dye in 2.0 M TEOA solution. We also
obtained the intersystem crossing rate of each xanthene dye in aqueous solution
with fluorescence quantum yield and lifetime measurements. Finally we found that
TEOA mainly interacts with the singlet excited-state of fluorescein,
dibromofluorescein, and eosin Y, and that TEOA can interact with both the singlet
and triplet excited-states of erythrosine B in high concentration of TEOA aqueous
solution.
PMID- 28499175
TI - Vibrational spectroscopic and computational studies on diisopropylammonium
bromide.
AB - Diisopropylammonium bromide (DIPAB) can be crystallized either in an orthorhombic
(P212121) or in a monoclinic (P21) structure at room temperature depending on
synthesis conditions. The non-polar orthorhombic structure exhibits a subtle,
irreversible transformation into the ferroelectric monoclinic-II (m-II) phase
above ~421K. At a slightly higher temperature of 426K this m-II (P21) phase
reversibly transforms into a disordered, paraelectric monoclinic-I (P21/m)
structure. We synthesized DIPAB in the orthorhombic structure, heated it to
obtain the m-II phase and carried out a systematic study of their Raman and IR
spectra. We obtained the phonon irreducible representations from factor group
analysis of the orthorhombic and m-II structures based on the reported structural
information. DIPAB is an organic molecular crystal, and the vibrational spectra
in the intramolecular region (200-3500cm-1) of the two different phases are
identical to each other, indicating weak inter-molecular interactions in both
crystalline structures. In the low wavenumber region (10-150cm-1) the Raman
spectra of the two phases are different due to their sensitivity to molecular
environment. We also carried out first principles calculations using Gaussian 09
and CASTEP codes to analyze the vibrational frequencies. Mode assignments were
facilitated by isolated molecule calculations that are also in good agreement
with intramolecular vibrations, whereas CASTEP (solid state) results could
explain the external modes.
PMID- 28499176
TI - Brain networks, structural realism, and local approaches to the scientific
realism debate.
AB - We examine recent work in cognitive neuroscience that investigates brain
networks. Brain networks are characterized by the ways in which brain regions are
functionally and anatomically connected to one another. Cognitive neuroscientists
use various noninvasive techniques (e.g., fMRI) to investigate these networks.
They represent them formally as graphs. And they use various graph theoretic
techniques to analyze them further. We distinguish between knowledge of the graph
theoretic structure of such networks (structural knowledge) and knowledge of what
instantiates that structure (nonstructural knowledge). And we argue that this
work provides structural knowledge of brain networks. We explore the significance
of this conclusion for the scientific realism debate. We argue that our
conclusion should not be understood as an instance of a global structural realist
claim regarding the structure of the unobservable part of the world, but instead,
as a local structural realist attitude towards brain networks in particular. And
we argue that various local approaches to the realism debate, i.e., approaches
that restrict realist commitments to particular theories and/or entities, are
problematic insofar as they don't allow for the possibility of such a local
structural realist attitude.
PMID- 28499177
TI - The dechlorination of pentachlorophenol under a sulfate and iron reduction co
occurring anaerobic environment.
AB - An anaerobic soil slurry incubation experiment was conducted by controlling
different Fe/S mole ratios (1/3, 1/2, 1/1, 2/1, 3/1, 8/1 and the control without
sulfate) through the addition of sodium sulfate, to investigate the effect of
sulfate and iron reduction on the reductive dechlorination of pentachlorophenol
(PCP). Two sequential incubation periods were carried out with the stage I
incubation conducted under a low electron donor concentration (0.5 mM lactate)
and stage II incubation conducted under increased electron donor supply with
lactate at 20 mM. During stage I, the production of Fe(II) occurred markedly
while sulfate reduction and PCP dechlorination rate were low, with the highest
dechlorination rates of PCP only 11.0% among all treatments at the end of stage I
incubation. During stage II, both PCP dechlorination and sulfate reduction were
greatly enhanced in all treatments, while the concentration of Fe(II) changed
slightly. The rate of PCP dechlorination decreased (from 87.7% to 34.2%) with the
increase of sulfate concentration (from Fe/S mole ratio of 8/1 to 1/3). Our study
suggested that the presence of a certain amount of sulfate might facilitate PCP
dechlorination in the range of Fe/S mole ratios greater than 1 when compared with
the control without SO42-. With the investigation of the dechlorination of PCP
under the Fe-S-PCP coexisting condition with different Fe/S mole ratios, our
study may provide improved strategy for optimizing the remediation of flooded
soils and sediments polluted by PCP.
PMID- 28499178
TI - Degradation of gaseous formaldehyde via visible light photocatalysis using multi
element doped titania nanoparticles.
AB - This study developed a modified titanium dioxide photocatalyst doped with multi
element synthesized via sol-gel process to productize a novel photocatalyst. The
study includes degradation of gaseous formaldehyde under visible light using the
synthesized novel titanium dioxide photocatalyst. Varying molar ratios from 0 to
2 percent (%mole in titanium dioxide) of ammonium fluoride, silver nitrate and
sodium tungstate as dopant precursors for nitrogen, fluorine, silver and tungsten
were used. Photodegradation of gaseous formaldehyde was examined on glass tubular
reactors illuminated with blue light emitting diodes (LEDs) using immobilized
photocatalyst. The photocatalytic yield is analyzed based on the photocatalyst
surface chemical properties via X-ray Photoelectron Spectroscopy (XPS), Fourier
Transform Infrared (FTIR) Spectrophotometry, Brunauer-Emmett-Teller (BET) and X
ray Diffraction (XRD) characterization results. The applied modifications
enhanced the visible light capability of the catalyst in comparison to the
undoped catalyst and commercially available Degussa P-25, such that it
photocatalytically degrades 88.1% of formaldehyde in 120 min. Synthesized
titanium dioxide photocatalyst exhibits a unique spin orbital at 532.07 eV and
533.27 eV that came from the hybridization of unoccupied Ti d(t2g) levels.
PMID- 28499179
TI - Fluorescent natural organic matter responsible for ultrafiltration membrane
fouling: Fate, contributions and fouling mechanisms.
AB - Membrane fouling has been a main obstacle to the success of ultrafiltration (UF)
technology. Recently, fluorescent natural organic matter (FNOM), including humic
like substances (HS) and protein-like substances, has been recognized as
substances responsible for membrane fouling. In this study, the matrix of FNOM in
natural river water was substantially modified by combined coagulation and
powdered activated carbon adsorption to enhance the diversity of the FNOM matrix.
Fluorescence excitation emission matrix spectroscopy was employed to characterize
FNOM components during the UF process. The correlations between FNOM components
of the feedwater and membrane fouling were evaluated for the initial period and
long-term operation. Reliable correlations of the maximum fluorescence intensity
of HS with initial membrane fouling indicated that HS were major foulants in the
initial period. Furthermore, the protein-like component exhibited significant
correlation with the concentration effect fouling (R2 = 0.6131) and with
irreversible fouling (R2 = 0.8711). We found that the fouling mechanism changed
from pore obstruction to a protein concentration polarization layer followed by
protein cake layer filtration. Total fouling of the UF membrane over long-term
operation was alleviated with powdered activated carbon (PAC) adsorption;
however, the mitigation of irreversible fouling was dependent on whether PAC
adsorbed protein-like substances.
PMID- 28499180
TI - Bioremediation of phenol in soil through using a mobile plant-endophyte system.
AB - Plant-endophyte remediation of volatile pollutants in soil is an emerging
technology. For more efficient application, plant-endophyte systems were formed
through stimulation of transfer of degradative plasmids in plant tissue by co
inoculation of corn, wheat or tomato seedlings with Pseudomonas fluorescens TP13
carrying a self-transmissible degradative plasmid, and P. fluorescens
streptomycin-resistant P13 strain. The corn-TP13-P13 (CTP) system had higher
degradation activity than other plant-endophyte systems. Transplanting the CTP,
from loam to sandy clay loam soil, from greenhouse to field trials, almost
completely removed phenol from contaminated soils in 15 d. Intact transplantation
of the CTP to contaminated soils was more efficient than co-transplanting of
phenol-degrading bacteria and plant in detoxification of phenol. After the
experiments the harvested CPT still exhibited remarkable bioremediation activity.
The number of degradative plasmid-carrying endophytic bacteria in the CTP system
was just slightly more than in the corn seedlings inoculated with TP13 alone, but
the former substantially surpassed the latter in phenol-degrading activity,
probably due to stimulation of transfer of the degradative plasmids among
endophytic bacteria in plant tissues. More degradative plasmid-carrying bacteria
colonized bioremediating soil and plant tissues, and higher plasmid transfer
frequency and C23O activity of transconjugant were found in soils for the CTP
system compared with other treatments. These results showed that the CTP system
is a valuable tool to degrade volatile organic pollutants and transfer of
degradative plasmids in plant tissues is important for construction of a mobile
plant-endophyte system applied in bioremediation of volatile pollutants.
PMID- 28499181
TI - Influence of temperature and pH on the anammox process: A review and meta
analysis.
AB - The anammox (anaerobic ammonium oxidation) process was considered a very
efficient and economic wastewater treatment technology immediately after its
discovery in 1995, thus research in this field was intensified. The anammox
process is characterised by a high temperature optimum and is very sensitive to
both temperature and pH fluctuations. The process can also be inhibited by many
factors, including by its substrates, i.e. nitrite and ammonium (or its unionised
forms: free ammonia and free nitrous acid). This paper presents a comprehensive
study of the most important and recent findings on the influence of two
parameters that are crucial in wastewater treatment, i.e. temperature and pH.
Because both parameters may influence the anammox process simultaneously, a meta
analysis was conducted of the data from the literature. Although meta-analysis is
commonly used in medical research, mathematical analysis of the literature data
has become an interesting and important step in the environmental sciences. This
paper presents information on the influence of both temperature and pH on process
efficiency and microbial composition. Additionally, the responses of different
operating systems on both temperature and pH changes are described. Moreover, the
role of both adaptation to changed conditions and of pH control as well as
indicated areas of process operation are discussed.
PMID- 28499182
TI - Perfluorooctane sulfonate adsorption on powder activated carbon: Effect of
phosphate (P) competition, pH, and temperature.
AB - Powdered activated carbon (PAC), as an adsorbent, was applied to remove
perfluorooctane sulfonate (PFOS) from aqueous solution. Laboratory batch
experiments were performed to investigate the influences of phosphate (P)
competition, temperature, and pH for PFOS adsorption onto PAC. The results showed
that higher temperature favored PFOS adsorption in single and binary systems. The
kinetic data fitted very well to the pseudo second-order kinetic model.
Thermodynamically, the endothermic enthalpy of the PFOS adsorption in single and
binary systems were 125.07 and 21.25 kJ mol-1, respectively. The entropy of the
PFOS adsorption in single and binary systems were 0.479 and 0.092 kJ mol-1 K-1,
respectively. And the Gibbs constants were negative. These results indicated that
the adsorption processes were spontaneous. The adsorption isotherms of PFOS
agreed well with the Langmuir model. In the single system, PFOS adsorption
decreased with increased pH value. The difference in the amount of PFOS
adsorption between the single and binary systems increased at higher pH.
Frustrated total internal reflection (FTIR) demonstrated that P competition
increased the hydrophilicity of the PAC and the electrostatic repulsion between
PFOS and PAC, then the PFOS adsorption amount decreased. It also demonstrated
that, at higher temperature, increased PFOS adsorption was mainly due to the
higher diffusion rate of PFOS molecules and greater number of active sites opened
on the PAC surface.
PMID- 28499183
TI - Contribution of filamentous fungi to the musty odorant 2,4,6-trichloroanisole in
water supply reservoirs and associated drinking water treatment plants.
AB - In this study, the distribution of 2,4,6-trichloroanisole (2,4,6-TCA) in two
water supply reservoirs and four associated drinking water treatment plants
(DWTPs) were investigated. The 2,4,6-TCA concentrations were in the range of 1.53
2.36 ng L-1 in water supply reservoirs and 0.76-6.58 ng L-1 at DWTPs. To
determine the contribution of filamentous fungi to 2,4,6-TCA in a full-scale
treatment process, the concentrations of 2,4,6-TCA in raw water, settled water,
post-filtration water, and finished water were measured. The results showed that
2,4,6-TCA levels continuously increased until chlorination, suggesting that 2,4,6
TCA could form without a chlorination reaction and fungi might be the major
contributor to the 2,4,6-TCA formation. Meanwhile, twenty-nine fungal strains
were isolated and identified by morphological and molecular biological methods.
Of the seventeen isolated fungal species, eleven showed the capability to convert
2,4,6-trichlorophenol (2,4,6-TCP) to 2,4,6-TCA. The highest level of 2,4,6-TCA
formation was carried out by Aspergillus versicolor voucher BJ1-3: 40.5% of the
original 2,4,6-TCP was converted to 2,4,6-TCA. There was a significant variation
in the capability of different species to generate 2,4,6-TCA. The results from
the proportions of cell-free, cell-attached, and cell-bound 2,4,6-TCA suggested
that 2,4,6-TCA generated by fungi was mainly distributed in their extracellular
environment. In addition to 2,4,6-TCA, five putative volatile by-products were
also identified by gas chromatography and mass spectrometry. These findings
increase our understanding on the mechanisms involved in the formation of 2,4,6
TCA and provide insights into managing and controlling 2,4,6-TCA-related problems
in drinking water.
PMID- 28499184
TI - Effects of graphite nanoparticles on nitrification in an activated sludge system.
AB - Graphite nanoparticles (GNPs) might result in unexpected effects during their
transportation and transformation in wastewater treatment systems, including
strong thermo-catalytic and catalytic effects and microbial cytotoxicity. In
particular, the effects of GNPs on the nitrification process in activated sludge
systems should be addressed. This study aimed to estimate the influence of GNPs
on the nitrification process in a short-term nitrification reactor with exposure
to different light sources. The results indicated that GNPs could only improve
the efficiency of photothermal transformation slightly in the activated sludge
system because of its photothermal effects under the standard illuminant
(imitating 1 * sun). However, even with better photothermal effects, the
nitrification efficiency still decreased significantly with GNP dosing under the
standard illuminant, which might result from stronger cytotoxic effects of GNPs
on the nitrifying bacteria. The disappearance of extracellular polymeric
substances (EPS) around bacterial cells was observed, and the total quantity of
viable bacteria decreased significantly after GNP exposuring. Variation in
bacterial groups primarily occurred in nitrifying microbial communities,
including Nitrosomonas sp., Nitrosospira sp., Comamonas sp. and Bradyrhizobiace
sp. Nitrifiers significantly decreased, while the phyla Gammaproteobacteria,
Deinocccus, and Bacteroidetes exhibited greater stability during GNP treatment.
PMID- 28499185
TI - Prevalence and profile of Neurodevelopment and Fetal Alcohol Spectrum Disorder
(FASD) amongst Australian Aboriginal children living in remote communities.
AB - BACKGROUND: Despite multiple risk factors for neurodevelopmental vulnerability,
few studies have assessed neurodevelopmental performance of Australian Aboriginal
children. An important risk factor for neurodevelopmental vulnerability is
prenatal alcohol exposure (PAE), which places children at risk for Fetal Alcohol
Spectrum Disorder (FASD). AIMS: This study assesses neurodevelopment outcomes in
a population of Australian Aboriginal children with and without PAE. METHODS AND
PROCEDURES: Children born in 2002/2003, and living in the Fitzroy Valley, Western
Australia between April 2010 and November 2011, were eligible (N=134).
Sociodemographic and antenatal data, including PAE, were collected by interview
with 127/134 (95%) consenting parents/caregivers. Maternal/child medical records
were reviewed. Neurodevelopment was assessed by clinicians blinded to PAE in
108/134 (81%) children and diagnoses on the FASD spectrum were assigned. OUTCOMES
AND RESULTS: Neurodevelopmental disorder was documented in 34/108 children (314.8
per 1000). Any diagnosis on the FASD spectrum was made in 21/108 (194.4 per 1000)
children (95% CI=131.0-279.0). CONCLUSIONS AND IMPLICATIONS: Neurodevelopmental
impairment with or without PAE is highly prevalent among children in the Fitzroy
Valley. Rates of diagnoses on the FASD spectrum are among the highest worldwide.
Early intervention services are needed to support developmentally vulnerable
children in remote communities.
PMID- 28499186
TI - Effect of betaine on hepatic insulin resistance through FOXO1-induced NLRP3
inflammasome.
AB - In the present study, we attempted to elucidate whether molecular modulation of
inflammation by betaine through the forkhead box O1 (FOXO1)-induced NLRP3
inflammasome improves insulin resistance. Betaine is a major water-soluble
component of Lycium chinense. It mainly functions as an oxidative metabolite of
choline by suppressing superoxide-induced free radicals by donating methyl
groups. The FOXO1 transcription factor regulates various genes involved in
cellular metabolic processes related to cell death as well as oxidative stress
responses through binding to the thioredoxin-interacting protein (TXNIP). Betaine
is known to inhibit FOXO1 phosphorylation through phosphoinositide 3-kinase
(PI3K)/protein kinase B (AKT) in liver cells exposed to insulin. To elucidate the
molecular mechanism of inactivation of insulin-induced FOXO1 by the antioxidant
betaine, we used HepG2 cells and the liver of db/db mice treated with betaine at
a dose of 50 mg/kg/day for 3 weeks. We found that the activation of NLRP3
inflammasome genes was reduced by betaine, which resulted in the suppression of
reactive species (RS) production in liver cells. In addition, betaine inhibited
insulin-induced PI3K/AKT and FOXO1 activation. Therefore, betaine suppressed the
cytokine interleukin-1beta production by inhibiting the activation of the NLRP3
inflammasome via interaction of FOXO1 and TXNIP. Our results suggest that betaine
inhibits the FOXO1 binding to TXNIP, leading to the suppression of RS-induced
NLRP3 inflammasome activation in a diabetic liver.
PMID- 28499187
TI - Vortioxetine: A review of the pharmacology and clinical profile of the novel
antidepressant.
AB - The aim of this paper was to review the up-to-date evidence base on pharmacology
and clinical properties of vortioxetine. Vortioxetine is a novel antidepressant,
approved by the US Food and Drug Administration (FDA) for the treatment of major
depressive disorder (MDD). Because vortioxetine exhibits both an antidepressant
and anxiolytic effect, it may be effective in treating both depressive and
anxiety disorders, such as generalized anxiety disorder (GAD). Based on its
pharmacodynamics profile and preclinical studies, it is believe that the drug's
clinical action is mediated mainly by selective blockade of serotonin reuptake
(by inhibiting the serotonin transporter [SERT]) and direct modulation of 5-HT
receptors activity (such as 5-HT3, 5-HT7, 5-HT1D and 5-HT1B). In patients with
MDD the recommended doses range is 5-20mg/day. Vortioxetine was shown to be more
effective than placebo both in MDD and GAD. In terms of side effects, nausea,
vomiting, diarrhea, and dry mouth were most commonly observed in individuals
receiving vortioxetine. In direct comparison to duloxetine, vortioxetine is found
to have a smaller efficacy but had a lower risk of developing the common
antidepressant-induced adverse effects.
PMID- 28499188
TI - PTP1B inhibitors from Selaginella tamariscina (Beauv.) Spring and their kinetic
properties and molecular docking simulation.
AB - Diabetes is one of the most popular worldwide diseases, regulated by the defects
in insulin secretion, insulin action, or both. The overexpression of protein
tyrosine phosphatase 1B (PTP1B) was found to down-regulate the insulin-receptor
activation. PTP1B has been known as a strategy for the treatment of diabetes via
the regulation of insulin signal transduction pathway. Herein, we investigated
the PTP1B inhibitors isolated from natural sources. The chemical investigation of
Selaginella tamariscina (Beauv.) Spring revealed seven unsaturated alkynyl
phenols 1-7, four new selaginellins T-W 1-4 together with three known compounds 5
7 isolated from the aerial parts. The structures of the isolates were determined
by spectroscopic techniques (1D/2D-NMR, MS, and CD). The inhibitory effects of
these isolates on the PTP1B enzyme activity were investigated. Among them,
compounds 2-7 significantly exhibited the inhibitory effects with the IC50 values
ranging from 4.8 to 15.9MUM. Compound 1 moderately displayed the inhibitory
activity with an IC50 of 57.9MUM. Furthermore, active compounds were discovered
from their kinetic and molecular docking analysis. The results revealed that
compounds 2 and 4-7 were mixed-competitive inhibitors, whereas compound 3 was a
non-competitive inhibitor. This data confirm that these compounds exhibited
potential inhibitory effect on the PTP1B enzyme activity.
PMID- 28499189
TI - Synthesis, biological evaluation and molecular modeling study of new (1,2,4
triazole or 1,3,4-thiadiazole)-methylthio-derivatives of quinazolin-4(3H)-one as
DHFR inhibitors.
AB - A new series of 2-mercapto-quinazolin-4-one analogues was designed, synthesized
and evaluated for their in vitro DHFR inhibition, antitumor and antimicrobial
activity. Compound 17 proved to be the most active DHFR inhibitor with IC50 value
of 0.01MUM, eight fold more active than methotrexate (MTX). Compounds 16 and 24
showed antitumor activity against human Caco2 colon and MCF-7 breast tumor cell
lines with IC50 values of 25.4 and 9.5MUg/ml, respectively. Compounds 15, 20, 21
and 30 showed considerable activity against the Gram-positive bacteria
Staphylococcus aureus while 24 and 30 proved active against Bacillus subtilis
with a magnitude of potency comparable to the broad spectrum antibiotic
Ciprofloxacin. Strong activity was observed for 13, 14, 19, 20 and 24 against
Candida albicans and Aspergillus flavus. Compound 17 shared a similar molecular
docking mode with MTX and made a critical hydrogen bond and arene-arene
interactions via Ala9 and Phe34 amino acid residues, respectively.
PMID- 28499190
TI - Ellagitannin and flavonoid constituents from Agrimonia pilosa Ledeb. with their
protein tyrosine phosphatase and acetylcholinesterase inhibitory activities.
AB - A new ellagitannin, agritannin (1), a new flavone glycoside, agriflavone (2), and
another flavone glycoside with spectroscopic data reported for the first time,
kaempferol-3-O-[(S)-3-hydroxy-3-methylglutaryl (1->6)]-beta-d-glucoside (3),
along with 16 known compounds were isolated from the aerial parts of Agrimonia
pilosa Ledeb. These compounds were evaluated for PTP1B inhibitory activity. Among
them, compounds 9 and 18 displayed potential inhibitory activity against PTP1B
with IC50 values of 7.14+/-1.75 and 7.73+/-0.24MUM, respectively. In addition,
compound 1 showed significant inhibitory effect with an IC50 value of 17.03+/
0.09MUM. Furthermore, these compounds were tested in AChE inhibitory assays. Most
of them were found to have moderate inhibitory effects, with IC50 values ranging
from 60.20+/-1.09 to 92.85+/-1.12MUM. Except compounds 3, 8, and 18 were
inactive.
PMID- 28499191
TI - Spatiotemporal signal classification via principal components of reservoir
states.
AB - Reservoir computing is a recently introduced machine learning paradigm that has
been shown to be well-suited for the processing of spatiotemporal data. Rather
than training the network node connections and weights via backpropagation in
traditional recurrent neural networks, reservoirs instead have fixed connections
and weights among the 'hidden layer' nodes, and traditionally only the weights to
the output layer of neurons are trained using linear regression. We claim that
for signal classification tasks one may forgo the weight training step entirely
and instead use a simple supervised clustering method based upon principal
components of reservoir states. The proposed method is mathematically analyzed
and explored through numerical experiments on real-world data. The examples
demonstrate that the proposed may outperform the traditional trained output
weight approach in terms of classification accuracy.
PMID- 28499192
TI - Handgrip strength is associated with anthropometrics variables and sex in
preschool children: A cross sectional study providing reference values.
AB - OBJECTIVE: The purpose of this study was to examine the influence of age, sex and
anthropometric variables in handgrip strength and to determine norm-referenced
values for preschool children. DESIGN: Cross-sectional study. SETTING: Schools.
PARTICIPANTS: A total of 1215 children, aged 3-6 years (590 girls and 625 boys).
INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Handgrip strength (HS),
measured by the CAMRY hydraulic hand dynamometer (EH101; Camry, Guangdong
Province, China). RESULTS: Boys exhibited a greater performance than girls in the
4 and 5 years age groups, but no significant differences were found at 3 and 6
years. In relation to growth, HS performance was greater with increased age. The
Pearson correlation analysis showed significant correlations between HS and body
mass (r = 0.354, p < 0.001), body height (r = 0.352, p < 0.001), body mass index
(r = 0.164, p < 0.001) and waist circumference (r = 0.118, p < 0.001).
CONCLUSION: This study provides references values for muscular strength
assessment by an HS test carried out on a large sample of preschoolers in
relation to age and sex. Additionally, some differences in HS performance were
found according to sex.
PMID- 28499193
TI - Stachydrine ameliorates isoproterenol-induced cardiac hypertrophy and fibrosis by
suppressing inflammation and oxidative stress through inhibiting NF-kappaB and
JAK/STAT signaling pathways in rats.
AB - Cardiac hypertrophy (CH), as one of the major causes of morbidity and mortality
in the world, has become an independent and predictive risk factor for adverse
cardiovascular events. However, progress in treatment remains sluggish in recent
years. Therefore, compounds derived from non-toxic nature plants are urgently
needed. Stachydrine (STA), which is isolated from Leonurus, has various
activities, including resistance to cardiovascular disease, but little is known
about its effect on CH or the mechanisms. We herein investigated the effect of
STA on isoproterenol-induced CH and the underlying mechanisms. Treatment with STA
significantly increased the ratios of heart weight/body weight, left ventricle
weight/body weight and the cross-sectional areas of cardiomyocytes. In addition,
STA significantly decreased the mRNA levels of atrial natriuretic peptide, B-type
natriuretic peptide and beta-myosin heavy chain. Furthermore, isoproterenol
induced fibrosis in rats receiving STA was significant attenuated, as evidenced
by decreased ratio of fibrotic area/total area and decreased mRNA levels of
collagens I and III. Given down-regulation of interleukin-6, tumor necrosis
factor-alpha, interferon-gamma (IFN-gamma) and IFN-1beta, treatment with STA
significantly reversed the expressions of pro-inflammatory induced by
isoproterenol. Moreover, STA attenuated the oxidative stress level in serum of
isoproterenol-induced CH rats, as shown by increased activity of superoxide
dismutase and decreased malondialdehyde level. STA inhibited the expressions of
phosphorylated IkappaBalpha, NF-kappaB p65, JAK2 and STAT3 in vivo. Thus, both NF
kappaB and JAK/STAT signalings played essential roles in mediating the anti-CH
effect of STA. Collectively, STA has a potent protective effect on isoproterenol
induced CH, with therapeutic implication for CH.
PMID- 28499194
TI - Quercetin ameliorates imiquimod-induced psoriasis-like skin inflammation in mice
via the NF-kappaB pathway.
AB - Quercetin (QC) is a dietary flavonoid abundant in many natural plants. A series
of studies have shown that it has been shown to exhibit several biological
properties, including anti-inflammatory, anti-oxidant, cardio-protective,
vasodilatory, liver-protective and anti-cancer activities. However, so far the
possible therapeutic effect of QC on psoriasis has not been reported. The present
study was undertaken to evaluate the potential beneficial effect of QC in
psoriasis using a generated imiquimod (IMQ)-induced psoriasis-like mouse model,
and to further elucidate its underlying mechanisms of action. Effects of QC on
PASI scores, back temperature, histopathological changes, oxidative/anti
oxidative indexes, pro-inflammatory cytokines and NF-kappaB pathway in IMQ
induced mice were investigated. Our results showed that QC could significantly
reduce the PASI scores, decrease the temperature of the psoriasis-like lesions,
and ameliorate the deteriorating histopathology in IMQ-induced mice. Moreover, QC
effectively attenuated levels of TNF-alpha, IL-6 and IL-17 in serum, increased
activities of GSH, CAT and SOD, and decreased the accumulation of MDA in skin
tissue induced by IMQ in mice. The mechanism may be associated with the down
regulation of NF-kappaB, IKKalpha, NIK and RelB expression and up-regulation of
TRAF3, which were critically involved in the non-canonical NF-kappaB pathway. In
conclusion, our present study demonstrated that QC had appreciable anti-psoriasis
effects in IMQ-induced mice, and the underlying mechanism may involve the
improvement of antioxidant and anti-inflammatory status and inhibition on the
activation of the NF-kappaB signaling. Hence, QC, a naturally occurring flavone
with potent anti-psoriatic effects, has the potential for further development as
a candidate for psoriasis treatment.
PMID- 28499195
TI - Using the Rubik's Cube to directly produce paper analytical devices for
quantitative point-of-care aptamer-based assays.
AB - In this article, we describe a facile method named as Rubik's Cube stamping (RCS)
for equipment-free fabrication of microfluidic paper-based analytical devices
(MUPADs). RCS is inspired by the worldwide ubiquitous RC toy and requires no
specialized electric equipment other than a classical six-faced RC that is
assembled with home-made small iron components. It can pattern various rosin
microstructures in paper simply by either using different functional faces of the
modified RC or applying its internal pivot mechanism to adjust the components'
patterning forms on one functional face. Such a versatile stamping method is
quite simple and inexpensive, and thus holds potential for producing rosin
patterned MUPADs by untrained users in resource-limited environments such as
small laboratories and private clinics, or even at home and in the field.
Moreover, a set of one-channel devices are fabricated to design a point-of-care
aptamer-based assay with near sample-in-answer-out capability that integrates
enzymatic reactions for robust yet efficient signal amplification and a personal
glucometer for portable, user-friendly, rapid and quantitative readout. Its
utility is well demonstrated with the sensitive and specific detection of
adenosine as a model target in buffer samples and undiluted human urine within
several minutes. With the advantages of low cost, simplicity, portability,
rapidity, and aptamer variety, this general point-of-care assay system reported
here may find broad applications including home healthcare, field-based
environmental monitoring or food analysis and emergency situations.
PMID- 28499196
TI - Binding-induced DNA walker for signal amplification in highly selective
electrochemical detection of protein.
AB - A binding-induced DNA walker-assisted signal amplification was developed for
highly selective electrochemical detection of protein. Firstly, the track of DNA
walker was constructed by self-assembly of the high density ferrocene (Fc)
labeled anchor DNA and aptamer 1 on the gold electrode surface. Sequentially, a
long swing-arm chain containing aptamer 2 and walking strand DNA was introduced
onto gold electrode through aptamers-target specific recognition, and thus
initiated walker strand sequences to hybridize with anchor DNA. Then, the DNA
walker was activated by the stepwise cleavage of the hybridized anchor DNA by
nicking endonuclease to release multiple Fc molecules for signal amplification.
Taking thrombin as the model target, the Fc-generated electrochemical signal
decreased linearly with logarithm value of thrombin concentration ranging from
10pM to 100nM with a detection limit of 2.5pM under the optimal conditions. By
integrating the specific recognition of aptamers to target with the enzymatic
cleavage of nicking endonuclease, the aptasensor showed the high selectivity. The
binding-induced DNA walker provides a promising strategy for signal amplification
in electrochemical biosensor, and has the extensive applications in sensitive and
selective detection of the various targets.
PMID- 28499197
TI - Biomolecular stiffness detection based on positive frequency shift of CMOS
compatible gigahertz solidly mounted resonators.
AB - In this work, gigahertz solidly mounted resonators (SMRs) (2.5GHz) were designed
and fabricated to construct a novel particle-resonator system to achieve the
biomolecular stiffness sensing in real time. The positive frequency shift of the
system was used to estimate the stiffness of biomolecules connecting between the
SMR and attached particles. The working principle was revealed by the
mathematical analysis of the general block-spring model of the system. Further
interpretations about the mechanism of such elastic interaction from the
perspective of acoustic resonant modes of SMRs were given by finite element
method. Biotin-streptavidin, antibody and antigen binding system were used as
model molecular linkers to study the frequency shift varied with different
particle diameters and particle densities. Different linker stiffness was
realized by adjusting the concentrations of antigens connected with particles
which form specific binding with antibodies immobilized on the SMR. The results
fairly agree with the simulation results demonstrating the proposed particle
resonator system as an effective method to realize the real-time biomolecular
stiffness detection.
PMID- 28499198
TI - A Point-of-Need infrared mediated PCR platform with compatible lateral flow strip
for HPV detection.
AB - With the increasing need of monitoring the epidemiology of serious infectious
diseases, food hygiene, food additives and pesticide residues, it is urgent to
develop portable, easy-to-use, inexpensive and rapid molecular diagnostic tools.
Herein, we demonstrate a prototype of IR mediated Conducting Oil and CarbOn
Nanotube circUlaTing PCR (IR-COCONUT PCR) platform for nucleic acid
amplification. The presented platform offers a new solution for miniaturized PCR
instruments with non-contact heaters by using conducting oil and carbon nanotube
as a medium in IR mediated PCR. This novel platform offers accurate and flexible
control of temperature through the integration of PID (proportional-integral
derivative) algorithms to manipulate the duty cycle of the voltage signals of IR
LED and a peristaltic pump. The ramping rate of the introduced platform in
current study is 1.5 degrees C/s for heating speed and -2.0 degrees C/s for
cooling speed. This platform fulfills 30 thermal cycles within 50min which is a
match to the conventional bench-top PCR thermo cyclers. For demonstration
purpose, human papillomavirus (HPV) patient cervical swab specimens were
examined. Downstream lateral flow strip (LFS) was also developed to quantity the
PCR products from the IR-COCONUT PCR device within 25min. This PCR platform
together with the compatible LFS shows great potential for in-field and Point-of
Need (PoN) testing of genetic or contagious diseases.
PMID- 28499199
TI - Perovskite-type calcium titanate nanoparticles as novel matrix for designing
sensitive electrochemical biosensing.
AB - In this work, novel perovskite-type calcium titanate nanoparticles (CaTiO3NPs)
were for the first time exploited for the immobilization of proteins and the
development of electrochemical biosensor. The CaTiO3NPs were synthesized with a
simple and cost-effective route at low temperature, and characterized by scanning
electron microscopy, X-ray photoelectron spectroscopic spectrum, electrochemical
impedance spectrum, UV-visible spectroscopy, Fourier transform infrared spectrum,
and cyclic voltammetry, respectively. The results indicated that CaTiO3NPs
exhibited large surface area, and greatly promoted the direct electron transfer
between enzyme molecules and electrode surface. The immobilized enzymes on this
matrix retained its native bioactivity and exhibited a surface controlled, quasi
reversible two-proton and two-electron transfer reaction with an electron
transfer rate of 3.35s-1. Using glucose oxidase as model, the prepared glucose
biosensor showed a high sensitivity of 14.10+/-0.5mAM-1 cm-2, a wide linear range
of 7.0*10-6 to 1.49*10-3M, and a low detection limit of 2.3*10-6M at signal-to
noise of 3. Moreover, the biosensor also possessed good reproducibility,
excellent selectivity and acceptable storage life. This research provided a new
type and promising perovskite nanomaterials for the development of efficient
biosensors.
PMID- 28499200
TI - Interactions of mussel-inspired polymeric nanoparticles with gastric mucin:
Implications for gastro-retentive drug delivery.
AB - Mussel-inspired polydopamine (pD) coatings have several unique characteristics
such as durability, versatility, and robustness. In this study, we have designed
pD-coated nanoparticles (NPs) of methoxy polyethylene glycol-b-poly(epsilon
caprolactone) (mPEG-PCL@pD) as prospective nanoscale mucoadhesive platforms for
gastro-retentive drug delivery. Successful pD coating on the NPs was confirmed by
Transmission Electron Microscopy and X-ray Photoelectron Spectroscopy.
Mucoadhesion of pD-coated NPs was investigated in vitro using commercially
available mucin under stomach lumen-mimetic conditions. Mucin-NP interactions
were monitored by dynamic light scattering, which showed a significant change in
particle size distribution of pD-coated NPs at mucin/NP ratios of 1:1, 1:2, and
1:4w/w. Turbidity measurements indicated the formation of large mucin-NP
aggregates causing a significant increase in turbidity at mucin/NP ratios of 2:1
and 4:1w/w. pD-coated NPs exhibited a significantly higher mucin adsorption
ability compared to uncoated NPs at mucin/NP ratios of 1:4, 1:2, and 1:1w/w. Zeta
potential measurements demonstrated that mucin-pD-coated NP interactions were not
electrostatic in nature. An ex vivo wash-off test conducted using excised sheep
stomach revealed that 78% of pD-coated NPs remained attached to the mucosa after
8h of incubation, compared to only 33% of uncoated NPs. In vitro release of
rifampicin, used as a model drug, showed a similar controlled release profile
from both pD-coated and uncoated NPs. Our results serve to expand the versatility
of mussel-inspired coatings to the design of mucoadhesive nanoscale vehicles for
oral drug delivery.
PMID- 28499201
TI - Folate-functionalized assembly of low density lipoprotein/sodium carboxymethyl
cellulose nanoparticles for targeted delivery.
AB - In this study, well-defined folate (FA)-functionalized low density lipoproteins
(LDL)/sodium carboxymethyl cellulose (CMC) nanoparticles (NP) were first
formulated, utilized in tumor targeting and pH-triggered drug release. CMC was
modified with FA before the preparation of NP. A model anti-tumor drug,
doxorubicin (DOX), was effectively loaded into the LDL/CMC-FA NP by ionic bonding
and hydrophobic interactions. To enhance non-covalent encapsulation stability,
self-assembly of DOX-loaded LDL/CMC-FA NP (NP-DOX) was cross-linked by
multivalent cations such as Ca2+ (Ca2+-NP-DOX). The active targeting efficiency
of NP-DOX and Ca2+-NP-DOX was tested against KB cells (FA-receptor over
expressing cells, FR+) and A549 cells (FA-receptor negative-expressing cells, FR
), using FA non-modified DOX-loaded LDL/CMC NP (NG-DOX) as control. The
competition assay proved that free FA molecules prevented the cellular uptake of
the NP by competitive binding to the FA receptors on the surface of KB cells.
This new pH-responsive and FA-targeted nanocarrier may be a promising efficient
drug delivery system for potential cancer therapy.
PMID- 28499202
TI - Novel dual VES phospholipid self-assembled liposomes with an extremely high drug
loading efficiency.
AB - Vitamin E succinate (VES), a unique selective anti-cancer drug, has attracted
much attention for its ability to induce apoptosis in various cancer cells.
Importantly, it has been reported that VES is largely non-toxic to normal cells.
However, poor aqueous solubility and bioavailability extensively restricted its
clinical utility. In this report, dual VES phospholipid conjugate (di-VES-GPC)
prodrug based liposomes were prepared in order to develop an efficient delivery
system for VES. Di-VES-GPC was first synthesized by conjugating VES with l-alpha
glycerophosphorylcholine (GPC) using N,N'-dicyclohexylcarbodiimide (DCC) as a
coupling agent. The di-VES-GPC prodrug was able to self-assemble into liposomes
by reverse-phase evaporation method. The structure of the liposomes was
characterized by dynamic light scattering (DLS), transmission electron microscopy
(TEM) and cryo-TEM. The results showed that di-VES-GPC assembled liposomes were
spherical with an average diameter approximately 183nm. Cryo-TEM data confirmed
the formation of multilamellar liposomes with the bilayer thickness about 5nm by
the assembly of the conjugate without any excipient. The VES drug loading highly
reaches up to 82.8wt% in the liposomes after a simple calculation. Furthermore,
the in vitro release behavior of di-VES-GPC liposomes was evaluated in different
media. It was found that the liposomes could release free VES at a weakly acidic
microenvironment but exhibited good stability under a simulated biological
condition. The cellular uptake and intracellular drug release tests demonstrated
that di-VES-GPC liposomes could be internalized effectively and converted into
parent drug VES in cancer cells. Furthermore, in vitro antitumor activities of
the di-VES-GPC liposomes were evaluated by MTT assay and flow cytometry. It was
revealed that the liposomes presented comparable cytotoxicities to free VES.
Taken together, the di-VES-GPC liposomes might provide an excellent formulation
of VES which have potential in the treatment of cancers.
PMID- 28499203
TI - Efficient protein digestion using immobilized trypsin onto tannin modified Fe3O4
magnetic nanoparticles.
AB - Fe3O4 magnetic nanoparticles (MNPs) were prepared via solvothermal method. A
commercially available trypsin was covalently immobilized onto MNPs modified with
tannin (T) via a novel binding process. The morphology, structure, surface and
magnetic properties of the obtained nanostructures were characterized
comprehensively. The Fe3O4 MNPs had a saturation magnetization value of
60.18emu/g at room temperature, while the tannin modified Fe3O4 MNPs, and the
trypsin immobilized on tannin modified-Fe3O4 MNPs possessed a saturation
magnetization value of 57.82emu/g and 55.16emu/g, respectively, which indicated
the decent tannin coating and trypsin immobilization. The general applicability
of the immobilized trypsin for proteomic studies was confirmed by enzymatic
digestion of widely used bovine serum albumin (BSA). The immobilized trypsin was
investigated by conducting the tryptic digestion of BSA within 1min, 5min and
15min. Also, microwave-assisted digestion was carried out for 15s. The digested
protein fragments were identified by matrix-assisted laser desorption/ionization
time of flight mass spectrometry (MALDI-TOF MS), and a satisfactory peptide
numbers of 39, and a superior sequence coverage of 84% for 1min digestion were
obtained. The sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS
PAGE) analysis confirmed the satisfactory digestion of BSA and egg white proteins
by immobilized trypsin.
PMID- 28499204
TI - Simultaneous determination of nine phytohormones in seaweed and algae extracts by
HPLC-PDA.
AB - An RP-HPLC-PDA method for the simultaneous analysis of 9 compounds deriving from
the phytohormones class was developed and optimized, namely indoleacetic acid
(IAA), indolebutyric acid (IBA), phenyleacetic acid (PAA), naphtyleacetic acid
(NAA), trans-zeatin (TZ), kinetin (KA), isopentenyladenine (IA), 6
benzylaminopurine (6-BA) and abscisic acid (ABA). Validation of the method was
performed on the SFE-CO2 extract made out of the mixture of Baltic algae. The
regression coefficients for plant hormones were in the range from 0.997 to 0.999.
The LOD and LOQ were on the levels from 0.05-0.29 and 0.15-0.88mg/L,
respectively. Developed method was used for the separation and determination
plant hormones in extracts obtained by SFE-CO2 (supercritical fluid extraction)
made out of the mixture of Baltic algae, Cladophora glomerata and Spirulina sp.
In the extract of Baltic seaweed 2 of tested compounds were present in the
concentration of 154,45+/-20,63MUg/g for TZ and 362,47+/-13,00MUg/g for PAA,
whereas in Cladophora glomerata extract contained PAA and IAA in the
concentration of 229,30+/-7,90MUg/g and 23,91+/-0,80MUg/g, respectively (all
values per g of extract). The differences in the hormones levels may occur due to
the different scale of extract preparation (laboratory or industrial) and other
factors like the place of algae collection, year of collection or the way of
biomass preparation.
PMID- 28499205
TI - Comparative metabolomics analysis for the compatibility and incompatibility of
kansui and licorice with different ratios by UHPLC-QTOF/MS and multivariate data
analysis.
AB - Kansui, the root of Euphorbia kansui T.N. Liou ex T.P. Wang (Euphorbiaceae), is a
well-known poisonous traditional Chinese medicine (TCM). However, many monographs
of TCM indicated that it cannot be co-used with licorice, as kansui-licorice is a
typical "eighteen incompatible" medicaments. Our previous studies have indicated
that kansui was effective in treating malignant pleural effusion (MPE), and the
efficacy could be weakened by the co-use of licorice, even causing serious
toxicity at the given ratio. Nevertheless, the actual mechanisms of their dosage
toxicity-efficacy relationship need to be well clarified. The present study aimed
to investigate the effect of individual and combined use of kansui and licorice
on MPE rats, and explain the underlying mechanisms from a metabolomic
perspective. Urine samples were analyzed by ultra-high-performance liquid
chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC
QTOF/MS). Partial least-squares discriminate analysis (PLS-DA) models were built
to evaluate the interaction between kansui and licorice. Seven potential
biomarkers contribute to the separation of model group and control group were
tentatively identified. And selenoamino acid metabolism and nicotinate and
nicotinamide metabolism with the impact-value 0.31 and 0.24, respectively, were
filtered out as the most important metabolic pathways. Kansui and kansui-licorice
at a ratio of 4:1 can treat MPE rats by adjusting abnormal metabolic pathways to
the normal state, while it may have opposite result with kansui-licorice 1:4. The
different influences to the two metabolic pathways may partially explain the
dosage-toxicity-efficacy relationship of kansui-licorice with different ratios.
The results could offer valuable insights into the compatibility property changes
for the two herbs.
PMID- 28499206
TI - Simultaneous determination of seven alkaloids from Rhizoma Corydalis Decumbentis
in rabbit aqueous humor by LC-MS/MS: Application to ocular pharmacokinetic
studies.
AB - This study aims to establish a fast and sensitive LC-MS/MS method for
simultaneous determination of seven alkaloids from Rhizoma Corydalis Decumbentis
in rabbit aqueous humor. Aqueous humor samples were processed by protein
precipitation and then separated on a Thermo Syncronis C18 column (50mm*2.1mm,
5MUm) with a mobile phase using acetonitrile-0.05% formic acid (28:72, v/v).
Detection of the analytes and the internal standard (coptisine) were performed in
positive electrospray ionization with selected reaction monitoring. The method
showed good linearity (r>0.9931) for all the seven alkaloids. This fully
validated method was applied to the studies of aqueous humor pharmacokinetics of
seven alkaloids from Rhizoma Corydalis Decumbentis and the effects of borneol on
corneal penetration of these alkaloids into aqueous humor. This is the first work
that presents a reliable LC-MS/MS method for simultaneous determination of seven
alkaloids in rabbit aqueous humor and its application of ocular pharmacokinetics
of seven alkaloids from Rhizoma Corydalis Decumbentis.
PMID- 28499207
TI - Thin high-order shims for small dipole NMR magnets.
AB - An NMR shim coil design method that addresses the severe spatial constraints of
miniaturized dipole magnets is introduced. The fundamental design element, a
collection of straight wires, is shown to be sufficient for producing a complete
set of shim fields of high mathematical order. In accord with these theoretical
considerations, a shim set is constructed using four wires in each of four
directions to create all first through fourth order fields, except one. This shim
set, with its supporting structure, occupies only 2mm of the available 5mm gap in
a small 1.6T magnet. However, the fields produced by the individual wires are
found to differ significantly from theoretical expectations. To produce the
desired harmonic shim fields, the magnetic field of each of the 32 wires is
mapped in three dimensions, and linear combinations of these maps are formed. The
resulting shim fields are found to be very pure. The shims are used in a
prototype high-resolution NMR magnet in which the 1.0mm sample size is only
possible due to the thinness of the shim set. The resulting spectra demonstrate
shimming to high resolution (<25ppb FWHM) without undue heating effects.
PMID- 28499208
TI - Whole-brain resting-state functional connectivity identified major depressive
disorder: A multivariate pattern analysis in two independent samples.
AB - BACKGROUND: there has been a recent increase in the use of connectome-based
multivariate pattern analysis (MVPA) of resting-state functional magnetic
resonance imaging (fMRI) data aimed at distinguishing patients with major
depressive disorder (MDD) from healthy controls (HCs). However, the validity of
this method needs to be confirmed in independent samples. METHOD: we used resting
state fMRI to explore whole-brain functional connectivity (FC) patterns
characteristic of MDD and to confirm the effectiveness of MVPA in distinguishing
MDD versus HC groups in two independent samples. The first sample set included 29
MDD patients and 33 HCs and second sample set included 46 MDD patients and 57
HCs. RESULTS: for the first sample, we obtained a correct classification rate of
91.9% with a sensitivity of 89.6% and specificity of 93.9%. For the second
sample, we observed a correct classification rate of 86.4% with a sensitivity of
84.8% and specificity of 87.7%. With both samples, we found that the majority of
consensus FCs used for MDD identification were located in the salience network,
default mode network, the cerebellum, visual cortical areas, and the affective
network. LIMITATION: we did not analyze potential structural differences between
the groups. CONCLUSION: results suggest that whole-brain FC patterns can be used
to differentiate depressed patients from HCs and provide evidence for the
potential use of connectome-based MVPA as a complementary tool in the clinical
diagnosis of MDD.
PMID- 28499209
TI - Precursors in adolescence of adult-onset bipolar disorder.
AB - BACKGROUND: Although the estimated contribution of genetic factors is high in
bipolar disorder, environmental factors may also play a role. This Swedish
register-based cohort study of men examined if physical and psychological
characteristics in late adolescence, including factors previously linked with
bipolar disorder (body mass index, asthma and allergy), are associated with
subsequent bipolar disorder in adulthood. Unipolar depression and anxiety are
analysed as additional outcomes to identify bipolar disorder-specific
associations. METHODS: A total of 213,693 men born between 1952 and 1956, who
participated in compulsory military conscription assessments in late adolescence
were followed up to 2009, excluding men with any psychiatric diagnoses at
baseline. Cox regression estimated risk of bipolar disorder, depression and
anxiety in adulthood associated with body mass index, asthma, allergy, muscular
strength stress resilience and cognitive function in adolescence. RESULTS: BMI,
asthma and allergy were not associated with bipolar disorder. Higher grip
strength, cognitive function and stress resilience were associated with a reduced
risk of bipolar disorder and the other disease outcomes. LIMITATIONS: The sample
consisted only of men; even though the characteristics in adolescence pre-dated
disease onset, they may have been the consequence of prodromal disease.
CONCLUSIONS: Associations with body mass index and asthma found by previous
studies may be consequences of bipolar disorder or its treatment rather than risk
factors. Inverse associations with all the outcome diagnoses for stress
resilience, muscular strength and cognitive function may reflect general risks
for these psychiatric disorders or intermediary factors.
PMID- 28499210
TI - Micro-scale environment and mental health in later life: Results from the
Cognitive Function and Ageing Study II (CFAS II).
AB - BACKGROUND: Poor micro-scale environmental features, such as graffiti and broken
windows, have been associated with crime and signs of social disorder with a
potential impact on mental health. The aim of this study is to investigate the
association between micro-scale environment and mental health problems in later
life, including cognitive (cognitive impairment and dementia) and common mental
disorders (depressive and anxiety symptoms). METHODS: The method of visual image
audits was used to collect micro-scale environmental data for 3590 participants
in the Cognitive Function and Ageing Study II, a population-based multicentre
cohort of people aged 65 or above in England. Multilevel logistic regression was
used to examine the associations between the quality of micro-scale environment
and mental health problems taking into account urban/rural difference. RESULTS:
Poor quality of micro-scale environment was associated with nearly 20% increased
odds of depressive (OR: 1.19; 95% CI: 0.99, 1.44) and anxiety symptoms (OR: 1.17;
95% CI: 0.99, 1.38) while the direction of association for cognitive disorders
differed across urban and rural settings. Although higher odds of cognitive
disorders were found in rural settings, living in a poor quality environment was
associated with nearly twice higher odds of cognitive impairment (OR: 1.88; 95%
CI: 1.18, 2.97) in urban conurbations but 20% lower odds in rural areas (OR:
0.80; 95% CI: 0.57, 1.11). LIMITATIONS: The causal direction could not be fully
determined due to the cross-sectional nature of the data. The visual nature of
the environmental assessment tool means it likely does not fully capture features
related to the availability of local support services, or opportunities for
social participation and interaction. CONCLUSIONS: The quality of micro-scale
environment appears to be important to mental health in older people.
Interventions may incorporate the environmental aspect to reduce cognitive and
common mental disorders.
PMID- 28499211
TI - Oxytocin receptor and G-protein polymorphisms in patients with depression and
separation anxiety.
AB - BACKGROUND: The impact of combined variants of Oxytocin Receptor (OXTR) and G
protein beta3 subunit genes was investigated in relation to retrospective reports
of childhood as well as contemporary adult separation anxiety (SA), based on
evidence of a beta/gamma dimer-mediated signaling for OXTR. METHODS: A case
control association study (225 healthy adults and 188 outpatients with
depression) was performed to establish Risk-Combined Genotype (RCG) of the
studied variants (OXTR rs53576 and the functional Gbeta3 subunit rs5443). Current
SA was evaluated by the ASA-27 and retrospective childhood symptoms by the SASI.
GG genotype of OXTR rs53576 combined with T-carrier genotype of Gbeta3 rs5443
represented the RCG. RESULTS: Compared to non-RCG, those with RCG had
significantly higher levels of childhood and adult SA. The RCG was significantly
associated with childhood SA threshold score (OR=2.85, 90%CI: 1.08-7.50).
Childhood SA was, in turn, strongly associated with a threshold SA score in
adulthood (OR=15.58; 95% CI: 4.62-52.59). LIMITATIONS: Although the overall
sample size is sizable, comparisons among subgroups with specific combination of
alleles are based on relatively small numbers. CONCLUSIONS: Our study indicates
that variations in OXTR and Gbeta3 genes are specifically associated with
presence and severity of SA in childhood and adulthood, but not with depression
or anxiety in general. Because there is increasing interest in oxytocin in social
behavior, the gene-SA associations identified have potential translational and
clinical relevance.
PMID- 28499212
TI - Quantification of Pasteurella multocida in experimentally infected pigs using a
real-time PCR assay.
AB - The aim of the study was to quantify Pasteurella multocida in experimentally
infected pigs using a new qPCR assay based on the sodA gene and validated with 35
P. multocida strains, including strains isolated from pigs with pneumonia,
clinically healthy pigs (nasal cavities), and human infections. The specificity
of the test was verified with a collection of 60 strains of bacterial species
other than P. multocida. The estimated detection threshold was 10 genome
equivalents per microliter. The amplification efficiency and value of the
correlation coefficients were 95.5% (+/-3.5%) and 0.995 (+/-0.005), respectively.
Analysis of P. multocida suspensions in Buffered Peptone Water Broth and of
samples prepared from lungs experimentally spiked with P. multocida revealed
detection thresholds of 1.4CFU/MUl and 8.4CFU/MUl, respectively. In live pigs,
experimentally-infected, approximately 105, 107 and 108genomeequivalents/ml of P.
multocida DNA was detected on Day 8 post-infection in the nasal cavities, tonsils
and trachea samples, respectively. In dead pigs, approximatively
107genomeequivalents/ml of P. multocida DNA was detected in the lung tissue with
pneumonia. The qPCR assay's diagnostic specificity and sensitivity were 100% and
96%, respectively. This new qPCR assay should be a very useful tool for
controlling enzootic pneumonia and studying the dynamics of infections in pig
herds.
PMID- 28499213
TI - Effect of Excoecaria agallocha on non-specific immune responses and disease
resistance of Oreochromis niloticus against Streptococcus agalactiae.
AB - The current study was designed to evaluate the effects of Excoecaria agallocha
leaf extracts on immune mechanisms and resistance of tilapia, Oreochromis
niloticus, after challenge with Streptococcus agalactiae. Fish were divided into
6 groups; groups 1-5 fed with E. agallocha leaf extracts at 10, 20, 30, 40 and
50mgkg-1 level, respectively. Group 6 were fed without extract addition and acted
as control. E. agallocha extracts were administered as feed supplement in fish
diet for 28days and the hematological, immunological, and growth performance
studies were conducted. Fish were infected with S. agalactiae at a dose of
15*105CFUmL-1 and the total white blood cell (WBC), phagocytosis and respiratory
burst activities of leukocytes, serum bactericidal activity, lysozyme, total
protein, albumin, and globulin levels were monitored and mortalities recorded for
15days post infection. Results revealed that feeding O. niloticus with 50mgkg-1
of E. agallocha enhanced WBC, phagocytic, respiratory burst, serum bactericidal
and lysozyme activities on day 28 pre-challenge and on 3rd, 6th, 9th, 12th and
15th day post-challenge as compared to control. Total protein and albumin were
not enhanced by E. agallocha diet. E. agallocha increased the survival of fish
after challenge with S. agalactiae. The highest mortality rate (97%) was observed
in control fish and the lowest mortality (27%) was observed with group fed with
50mgkg-1 extract. The results indicate that dietary intake of E. agallocha
methanolic leaf extract in O. niloticus enhances the non-specific immunity and
disease resistance against S. agalactiae pathogen.
PMID- 28499214
TI - Speciation of potential anti-diabetic vanadium complexes in real serum samples.
AB - In this work the speciation in real serum samples of five VIVO complexes with
potential application in the therapy of diabetes was studied through EPR
spectroscopy as a function of V concentration (45.4, 90.9 and 454.5MUM) and time
(0-180min). [VO(dhp)2], [VO(ma)2], [VO(acac)2], [VO(pic)2(H2O)], and
[VO(mepic)2], where Hdhp indicates 1,2-dimethyl-3-hydroxy-4(1H)-pyridinone, Hma
maltol, Hacac acetylacetone, Hpic picolinic acid, and Hmepic 6-methylpicolinic
acid, were examined. The distribution of VIVO2+ among the serum bioligands was
calculated from the thermodynamic stability constants in the literature and
compared with the experimental results. EPR results, which confirm the
prediction, depend on the strength of the ligand L and geometry assumed by the
bis-chelated species at physiological pH, cis-octahedral or square pyramidal.
With dhp, the strongest chelator, the system is dominated by [VO(dhp)2] and/or
cis-VO(dhp)2(Protein); with intermediate strength chelators, i.e. maltolate,
acetylacetonate and picolinate, by cis-VO(ma)2(Protein), [VO(acac)2] or
[VO(pic)(citrH-1)]3-/[VO(pic)(lactH-1)]- (citr=citrate and lact=lactate) when the
V concentration overcomes 100-200MUM and by (VO)(hTf)/(VO)2(hTf) when
concentration is lower than 100MUM; with the weakest chelator, 6
methylpicolinate, (VO)(hTf)/(VO)2(hTf), (VO)(HSA) (hTf = human serum transferrin
and HSA = human serum albumin), and VO(mepic)(Protein)(OH) are the major species
at concentration higher than 100-200MUM, whereas hydrolytic processes are
observed for lower concentrations. For [VO(dhp)2], [VO(ma)2], [VO(acac)2] and
[VO(pic)2(H2O)], the EPR spectra remain unaltered with elapsing time, while for
mepic they change significantly because the hydrolyzed VIVO species are complexed
by the serum bioligands, in particular by lactate. The rate of oxidation in the
serum is [VO(dhp)2]>[VO(ma)2]>[VO(acac)2] and reflects the order of E1/2 values.
PMID- 28499215
TI - Numerical study on the air conditioning characteristics of the human nasal
cavity.
AB - The air-conditioning characteristics of the human nasal cavity were investigated
using computational fluid dynamics. The wall layer was modeled as a heat
conducting layer consisting of water with constant thickness placed on top of
epithelial cells. By assuming constant tissue temperature, prescribed to be 36
degrees C, which is close to the alveolar condition, the proposed wall model
yielded a spatially varying surface temperature distribution that is in
reasonable agreement with the measurement studies in the literature. The results
show that the regions of the main airway between the nasal valve, and the
anterior of the middle turbinate were shown to have relatively low temperatures,
whereas the superior meatus exhibited relatively high temperature. Water vapor
flux evaluated at the surface of the mucus layer was found to be quite large in
the region between the posterior of the vestibule and the anterior of the middle
turbinate. Comparing the results obtained from the present model to those
obtained with a constant surface temperature boundary condition of 32.6 degrees
C or 34 degrees C revealed that temperature, and absolute humidity of the
airflow increased faster through the turbinated airway passage. Even in the
presence of sizable differences in the distributions of surface temperature and
water vapor concentration, distributions of relative humidity of the air were
found to be quite similar regardless of temperature boundary conditions.
PMID- 28499216
TI - Biobrick chain recommendations for genetic circuit design.
AB - Synthetic biology databases have collected numerous biobricks to accelerate
genetic circuit design. However, selecting biobricks is a tough task. Here, we
leverage the fact that these manually designed circuits can provide underlying
knowledge to support biobrick selection. We propose to design a recommendation
system based on the analysis of available genetic circuits, which can narrow down
the biobrick selection range and provide candidate biobricks for users to choose.
A recommendation strategy based on a Markov model is established to tackle this
issue. Furthermore, a biobrick chain recommendation algorithm Sira is proposed
that applies a dynamic programming process on a layered state transition graph to
obtain the top k recommendation results. In addition, a weighted filtering
strategy, WFSira, is proposed to augment the performance of Sira. The
experimental results on the Registry of Standard Biological Parts show that Sira
outperforms other algorithms significantly for biobrick recommendations, with
approximately 30% improvement in terms of recall rate. It is also able to make
biobrick chain recommendations. WFSira can further improve the recall rate of
Sira by an average of 7.5% for the top 5 recommendations.
PMID- 28499217
TI - Adhesive coatings based on melanin-like nanoparticles for surgical membranes.
AB - Adhesive coatings for implantable biomaterials can be designed to prevent
material displacement from the site of implant. In this paper, a strategy based
on the use of melanin-like nanoparticles (MNPs) for the development of adhesive
coatings for polysaccharidic membranes was devised. MNPs were synthesized in
vitro and characterized in terms of dimensions and surface potential, as a
function of pH and ionic strength. The in vitro biocompatibility of MNPs was
investigated on fibroblast cells, while the antimicrobial properties of MNPs in
suspension were evaluated on E. coli and S. aureus cultures. The manufacturing of
the adhesive coatings was carried out by spreading MNPs over the surface of
polysaccharidic membranes; the adhesive properties of the nano-engineered coating
to the target tissue (intestinal serosa) were studied in simulated physiological
conditions. Overall, this study opens for novel approaches in the design of
naturally inspired nanostructured adhesive systems.
PMID- 28499218
TI - Dissolution and physicochemical stability enhancement of artemisinin and
mefloquine co-formulation via nano-confinement with mesoporous SBA-15.
AB - The objective of this study is to enhance the dissolution rate, supersaturation
and physicochemical stability of combination of two poorly water-soluble anti
malarial drugs, artemisinin (ART) and mefloquine (MFQ), by encapsulating them
inside mesoporous silica (SBA-15) via co-spray drying. Characteristic studies
such as powder X-ray diffraction (PXRD), transmission electron microscopy (TEM)
and scanning electron microscope (SEM) clearly indicate the amorphization of the
crystalline drugs. ART/MQF/SBA-15 formulations show a superior dissolution
enhancement with a burst release of more than 95% of drugs within 30min. In
addition, the combination formulation exhibits a stable supersaturation
enhancement by 2-fold higher than that of the untreated crystalline counterparts.
ART/MQF/SBA-15 samples possess excellent physicochemical stability under 2
different moderate storage conditions for 6 months. The amorphization of ART and
MFQ via nano-confinement using mesoporous SBA-15 is a potentially promising
approach to enhance the solubility of poorly water-soluble anti-malarial drugs
that co-formulated into a single dosage form.
PMID- 28499219
TI - Oxidant and anti-oxidant status in common brain tumors: Correlation to TP53 and
human biliverdin reductase.
AB - OBJECTIVE: To assess oxidant and antioxidant status in patients with common brain
tumors; namely meningiomas, low-grade gliomas (LGG) and high-grade gliomas (HGG)
and to compare with normal brain tissues. PATIENTS AND METHODS: Almost nine
biomarkers were measured in 59 brain tumors obtained during surgery and 15 normal
brain tissues that were collected during autopsy. Results were compared between
two groups. RESULTS: In general, protein oxidation and lipid peroxidation
increased while antioxidant capacity decreased significantly in tumors compared
to the controls (p<0.05) and higher the grade of the tumor, higher the levels of
oxidation and lower the anti-oxidation. CONCLUSIONS: Reactive oxygen species may
play a crucial role in the pathogenesis of these common brain tumors. As the
processes at the molecular level understood, targeted-treatment adjunct to
surgical removal will be possible to cope with these devastating brain tumors.
PMID- 28499220
TI - Effects of preadmission beta-blockers on neurogenic stunned myocardium after
aneurysmal subarachnoid hemorrhage: A meta- analysis.
AB - OBJECTIVE: Spontaneous subarachnoid hemorrhage is mostly caused by the rupture of
an aneurysm. Neurogenic stunned myocardium (NSM) is one of the most frequent
complications caused by aneurysmal subarachnoid hemorrhage (aSAH). The possible
pathogenesis of NSM may be that the catecholamine peak resulting from aSAH leads
to subendocardial ischemia or coronary artery spasm. We designed this meta
analysis to find out whether beta-blockers (BB) can significantly reduce the
incidence of NSM and improve the outcomes of aSAH. PATIENTS AND METHODS: We
systematically searched PubMed, Embase, Cochrane library, Elsevier and Medline
from inception to Feb 2016. All studies related to the preadmission beta-blocker
with aSAH were included. RESULTS: Three retrospective studies and 691 patients
were included. The incidence of mortality [OR=0.68, 95%CI (0.08-3.50), P=0.57],
cardiac dysfunction [OR = 0.55, 95% CI (0.05-6.49), P=0.63], cerebral vasospasm
(OR=0.52 95% CI(0.18-2.56), P=0.50] had no statistical difference between the
preadmission BB group and no BB group. CONCLUSION: The preadmission beta-blocker
cannot decrease the incidence of mortality, cardiac dysfunction, cerebral
vasospasm in patients with aSAH. A further research of the usefulness of
preadmission beta-blocker in patients with aSAH will be needed.
PMID- 28499221
TI - A water quality management strategy for regionally protected water through health
risk assessment and spatial distribution of heavy metal pollution in 3 marine
reserves.
AB - Severe water pollution and resource scarcity is a major problem in China, where
it is necessary to establish water quality-oriented monitoring and intelligent
watershed management. In this study, an effective watershed management method is
explored, in which water quality is first assessed using the heavy metal
pollution index and the human health risk index, and then by classifying the
pollution and management grade based on cluster analysis and GIS visualization.
Three marine reserves in Tianjin were selected and analyzed, namely the Tianjin
Ancient Coastal Wetland National Nature Reserve (Qilihai Natural Reserve), the
Tianjin DaShentang Oyster Reef National Marine Special Reserve (DaShentang
Reserve), and the Tianjin Coastal Wetland National Marine Special Reserve (BinHai
Wetland Reserve) which is under construction. The water quality and potential
human health risks of 5 heavy metals (Pb, As, Cd, Hg, Cr) in the three reserves
were assessed using the Nemerow index and USEPA methods. Moreover, ArcGIS10.2
software was used to visualize the heavy metal index and display their spatial
distribution. Cluster analysis enabled classification of the heavy metals into 4
categories, which allowed for identification of the heavy metals whose pollution
index and health risks were highest, and, thus, whose control in the reserve is a
priority. Results indicate that heavy metal pollution exists in the Qilihai
Natural Reserve and in the north and east of the DaShentang Reserve; furthermore,
human health risks exist in the Qilihai Natural Reserve and in the BinHai Wetland
Reserve. In each reserve, the main factor influencing the pollution and health
risk were high concentrations of As and Pb that exceed the corresponding
standards. Measures must be adopted to control and remediate the pollutants.
Furthermore, to protect the marine reserves, management policies must be
implemented to improve water quality, which is an urgent task for both local and
national governments.
PMID- 28499222
TI - The actual role of oxygen deficit in the linkage of the water quality and benthic
phosphorus release: Potential implications for lake restoration.
AB - Human activities in watersheds have resulted in huge accumulations of phosphorus
(P) in sediments that have subsequently hindered restoration efforts of lake
water quality managers worldwide. Much controversy exists about the factors that
control the release of P from sediments (internal P loading). One of the main
debates concerns the role of oxygen deficit (anoxia) in the regulation of water
quality. Our results based on a comprehensive set of lakes worldwide demonstrate
that internal P loading (IPtot) plays a significant role in water quality
regulation. Internal P loading due to anoxia (IPanox) contributes significantly
to the IPtot. However, this contribution is insufficient to significantly
increase the chlorophyll a (Chl a) concentration in stratifying lakes. In the
lakes of the north temperate and boreal zone, this is because the IPanox reaches
surface water layer in the end of the growing season. Observed water quality
implications of IPtot are most likely caused by the sedimentary P that actually
originates from the shallow areas. These findings suggest limitations for the use
of aeration (improvement of the oxygen conditions in the hypolimnion) in lake
water quality restoration. Moreover, lake ecosystem managers can benefit from our
model that enables to predict anoxia triggered sedimentary P release from the
combination of lake characteristics. The final decision on the use of aeration is
indeed unique to each lake, and lake specific targets should be considered.
PMID- 28499223
TI - Decomposing the land-use specific response of plant functional traits along
environmental gradients.
AB - Environmental conditions affect functional trait variability within communities
and thus shape ecosystem properties. With the ability of plants to adapt
morphologically and physiologically to changing abiotic conditions, gradient
analysis was shown to be a suitable tool to identify the drivers which determine
trait values. Apart from direct environmental drivers and indirect gradients such
as elevation, also anthropogenic effects (e.g. irrigation, grazing) can influence
trait variability. Our aim was to assess the interactive effects of different
environmental drivers on major plant traits and to investigate how these are
modulated within two different land-use types (hay meadow vs. pasture). An
elevational gradient spanning 1000m was decomposed into its underlying direct
components (temperature, water input, length of growing season) for the
investigation of gradual responses of five prominent functional traits
(aboveground dry weight (AGDW), vegetative height (VegHt), specific leaf area
(SLA), leaf dry matter content (LDMC), leaf nitrogen concentration (LNC)) for key
species from two functional groups (grasses, forbs) in the two land
use/management regimes. The present study revealed that the detailed analysis of
single direct gradients provides substantial additional information on trait
response which remains hidden or is even reversed if only indirect gradients such
as elevation are analysed. However, trait response to the combination of the
three direct gradients aligned surprisingly well with trait response to the
indirect gradient underpinning the adequate representation of temperature, water
input and length of growing season by elevation. The response of traits
significantly depended on the management regime and corresponding intensity which
was shown to play an overriding role and constrained and attenuated response
ranges of traits to climatic gradients.
PMID- 28499224
TI - Interspecies comparison of selected pollution biomarkers in dreissenid spp.
inhabiting pristine and moderately polluted sites.
AB - Stress biomarkers, which can outline impacts of contaminants in aquatic biota at
the biochemical level, are increasingly used as early warning tools in
environmental monitoring. Reliable biomarker based assessment schemes, however,
request appropriate knowledge of baseline levels of selected endpoints, and the
potential influence of a range of natural influencing factors (both abiotic and
biotic) as well. In this study, we examined the interspecies variability of
various biomarkers (metallothioneins (MT), ethoxyresorufin-O-deethylase activity
(EROD), lipid peroxidation (LPO), DNA strand breaks (DNA_sb), vitellogenin-like
proteins (Vtg)) in Dreissena polymorpha and Dreissena bugensis inhabiting either
pristine- or moderately impacted sites of Lake Balaton (Hungary). Levels of all
biomarkers considered revealed low interspecies variability in the two dreissenid
species at all sampling sites, with consistently higher (but statistically
insignificant) values in Dreissena polymorpha. Levels of all biomarkers varied
within the two investigated seasons, with significant influence of the
reproduction cycle particularly on the levels of metallothioneins and
vitellogenin-like proteins. Each biomarker considered was elevated by October,
with significantly higher values in the mussels inhabiting harbours.
Insignificant spatial and temporal variability in the general health indicators
(condition index, total protein content) of dreissenids was observed, which, in
parallel with evident rise in biomarker levels, apparently suggest that the
anthropogenic impacts in harbours affect mussel fitness yet at sub organismal
level. Our data might serve useful basis for future environmental monitoring
surveys, especially in habitats where the progressive replacement of Dreissena
polymorpha by Dreissena bugensis is taking place, as the interspecies variability
in susceptibility to chemical stress of the two species is well comparable.
PMID- 28499225
TI - Environmental risk assessment of polycyclic musks HHCB and AHTN in consumer
product chemicals in China.
AB - An environmental risk assessment (ERA) framework was recently developed for
consumer product chemicals in China using a tiered approach, applying an existing
Chinese regulatory qualitative method in Tier Zero and, then, utilizing
deterministic and probabilistic methods for Tiers One and Two. The exposure
assessment methodology in the framework applied conditions specific to China
including physical setting, infrastructure, and consumers' habits and practices.
Furthermore, two scenarios were identified for quantitatively assessing
environmental exposure: (1) Urban with wastewater treatment, and; (2) Rural
without wastewater treatment (i.e., direct-discharge of wastewater). Upon a brief
discussion on the framework methodology, this paper primarily presented a case
study conducted using this new approach for assessing two fragrance chemicals,
the polycyclic musks HHCB (Galaxolide, 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8
hexamethylcyclopenta-[gamma]-2-benzopyran) and AHTN (Tonalide, 7-acetyl
1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene). Both HHCB and AHTN are
widely used as fragrances in a variety of consumer products in China, and
occurrences of both compounds have been reported in wastewater influents,
effluents, and sludge, in addition to surface water and sediments across several
major metropolitan regions throughout China. This case study illustrated the very
conservative nature of Tier Zero, which indicated a high risk potential of the
fragrances to receiving water aquatic communities due to the fragrance's non
ready biodegradability and eco-toxicity profiles. However, the higher-tiered
assessments (including deterministic and site-specific probabilistic)
demonstrated greater environmental realism with the conclusion of HHCB and AHTN
posing minimal risk, consistent with local monitoring data as well as a recent
similar study conducted in the United States.
PMID- 28499226
TI - Effectiveness of a full-scale horizontal slow sand filter for controlling
phytopathogens in recirculating hydroponics: From microbial isolation to full
microbiome assessment.
AB - The microbial disinfestation efficiency of an innovative horizontal-flow slow
sand filter (HSSF) for treating nutrient solution spent from an experimental
closed-loop nursery was evaluated by means of a combination of culture-dependent
and independent molecular techniques. A dense inoculum of the fungal plant
pathogen Fusarium oxysporum f.sp. lycopersici was applied in the fertigation
system (106 cells per mL). Indigenous and introduced populations of eubacteria
and fungi were assessed in the nutrient solution, the HSSF influent/effluent, and
a sand bed transect by isolation on selective media, as well as by quantitative
qPCR and next-generation sequencing (NGS) on target ribosomal genes. The HSSF
effectively reduced viable Fusarium propagules and fungal gene content with an
efficiency consistently above 99.9% (5 orders of magnitude down). On the other
hand, Fusarium cells accumulated in the sand bed, indicating that physical
entrapment was the main removal mechanism. The viability of retained Fusarium
cells tended to decrease in time, so that treatment efficiency might be enhanced
by antagonistic species from the genera Bacillus, Pseudomonas, and Trichoderma,
also identified in the sand bed. Indigenous bacterial populations from the HSSF
effluent were reduced by 87.2% and 99.9% in terms of colony forming units and
gene counts, respectively, when compared to the influent. Furthermore, microbial
populations from the HSSF effluent were different from those observed in the sand
bed and the influent. In summary, the HSSF microbial disinfestation efficiency is
comparable to that reported for other more intensive and costly methodologies,
while allowing a significant recovery of water and nutrients.
PMID- 28499227
TI - Organic carbon pools and soil biological fertility are affected by land use
intensity in Mediterranean ecosystems of Sardinia, Italy.
AB - Soil quality is mainly studied from the chemical and physical point of view,
whereas soil biochemical and microbiological parameters are relatively more
scarcely explored to assess the effect of management practices. This study aimed
to evaluate soil organic carbon (SOC) and its pools; soil microbial activity
parameters; and the Biological Fertility Index (BFI), in six land uses
characteristics of the Mediterranean basin in north-eastern Sardinia. These land
uses differed in management intensity and consisted of: tilled vineyard (TV), no
tilled grassed vineyard (GV), former vineyards (FV), hay crop and pasture (HC and
PA), cork oak forest (CO). Significant differences among ecosystems were found in
most cases in (SOC), the related pools (total extractable carbon, humic and
fulvic acids, not humified, not extractable), humification parameters (degree,
rate and index of humification), and soil microbial activity (microbial carbon,
respiration, metabolic quotient, and mineralization quotient). Pasture and cork
oak forest showed in average a better soil quality for most biochemical and
microbial parameters in comparison with the other ecosystems. The index of soil
biological fertility (BFI) was higher under cork oak forest which is supposed to
be the most sustainable ecosystem in the long term in this environment, able to
maintain soil biological fertility and microbial diversity.
PMID- 28499228
TI - Imprisoned in the Cretan mountains: How relict Zelkova abelicea (Ulmaceae) trees
cope with Mediterranean climate.
AB - We investigate the sensitivity of the relict, endemic Cretan tree species Zelkova
abelicea (Lam.) Boiss. (Ulmaceae) to several climate variables (temperature,
precipitation and drought). For this purpose, we establish the first centennial
tree-ring chronology for the species, and the first ever tree-ring chronology for
a broadleaved species on Crete. We demonstrate the strong sensitivity of Z.
abelicea towards precipitation and drought in late spring to early summer and the
absence of a significant response to abundant precipitation occurring during
winter or early spring. Whereas the late spring sensitivity is strong and
consistent through time, the species seems to be experiencing a loss of signal
towards early summer conditions since the 1970s, interpreted as an earlier
cessation of cambial activity due to the increase in summer drought conditions on
Crete. However, despite a reduced vegetative period, no significant decrease in
radial growth of Z. abelicea was observed in the tree-ring series for the last
decades, thus highlighting the capacity of Z. abelicea to withstand changing
environmental conditions.
PMID- 28499229
TI - Operational integration of time dependent toxicity impact category in dynamic
LCA.
AB - Life Cycle Assessment (LCA) is the most widely used method for the environmental
evaluation of an anthropogenic system and its capabilities no longer need to be
proved. However, several limitations have been pointed out by LCA scholars,
including the lack of a temporal dimension. The objective of this study is to
develop a dynamic approach for calculating the time dependent impacts of human
toxicity and ecotoxicity within LCA. A new framework is proposed, which includes
dynamic inventory and dynamic impact assessment. This study focuses on the
dynamic fate model for substances in the environment, combined with the USEtox(r)
model for toxicity assessment. The method takes into account the noisy and random
nature of substance emissions in function of time, as in the real world, and uses
a robust solver for the dynamic fate model resolution. No characterization
factors are calculated. Instead, a current toxicity is calculated as a function
of time i.e. the damage produced per unit of time, together with a time dependent
cumulated toxicity, i.e. the total damage produced from time zero to a given time
horizon. The latter can be compared with the results obtained by the conventional
USEtox(r) method: their results converge for a very large time horizon
(theoretically at infinity). Organic substances are found to disappear relatively
rapidly from the environmental compartments (in the time period in which the
emissions occur) while inorganic substances (i.e. metals) tend to persist far
beyond the emission period.
PMID- 28499230
TI - Species complexes within epiphytic diatoms and their relevance for the
bioindication of trophic status.
AB - The popularity of aquatic bioassessments has increased in Europe and worldwide,
with a considerable number of methods being based on benthic diatoms. Recent
evidence from molecular data and mating experiments has shown that some
traditional diatom morphospecies represent species complexes, containing several
to many cryptic species. This case study is based on epiphytic diatom and
environmental data from shallow fishponds, investigating whether the recognition
and use of fine taxonomic resolution (cryptic species) can improve assessment of
community response to environmental drivers and increase sharpness of
classification, compared to coarse taxonomic resolution (genus level and species
level with unresolved species complexes). Secondly, trophy bioindication based on
a species matrix divided into two compartments (species complexes and remaining
species) was evaluated against the expectation that species complexes would be
poor trophy indicators, due to their expected wide ecological amplitude. Finally,
the response of species complexes and their members (cryptic species) to a
trophic gradient (phosphorus) were compared. Multivariate analyses showed similar
efficiency of all three taxonomic resolutions in depicting community patterns and
their environmental correlates, suggesting that even genus level resolution is
sufficient for routine bioassessment of shallow fishponds with a wide trophic
range. However, after controlling for coarse taxonomic matrices, fine taxonomic
resolution (with resolved cryptic species) still showed sufficient variance
related to the environmental variable (habitat groups), and increased the
sharpness of classification, number of indicator species for habitat categories,
and gave better separation of habitat categories in the ordination space.
Regression analysis of trophic bioindication and phosphorus concentration showed
a weak relationship for species complexes but a close relationship for the
remaining taxa. GLM models also showed that no species complex responded to
phosphorus concentration. It follows that the studied species complexes have wide
tolerances to, and no apparent optima for, phosphorus concentrations. In
contrast, various responses (linear, unimodal, or no response) of cryptic species
within species complexes were found to total phosphorus concentration. In some
cases, fine taxonomic resolution to species level including cryptic species has
the potential to improve data interpretation and extrapolation, supporting recent
views of species surrogacy.
PMID- 28499231
TI - Radiofrequency electromagnetic fields and some cancers of unknown etiology: An
ecological study.
AB - Simultaneously with the increase of Radiofrequency Electromagnetic Fields (RF
EMF) in recent decades, there has been increasing concern about their potential
relation with the etiology of several tumors. At this time, the techniques of
spatial data analysis jointly with the study of the personal exposure to these
fields offer a new approach to the problem. This paper presents the results of a
preliminary epidemiological study, combining Epidemiology, Statistics and
Geographical Information Systems (GIS), in which we analyzed the correlation
between exposure to RF-EMF in the city of Albacete (166,000 inhabitants,
southeast Spain) and the incidence of several cancers with unspecific causes
(lymphomas, and brain tumors). We used statistical tools to analyze the spatial
point patterns and aggregate data with the aim to study the spatial randomness
and to determine the zones with the highest incidence from 95 tumors studied (65
lymphomas, 12 gliomas and 18 meningiomas). We also perform a correlation
(Spearman) study between the personal exposure to RF-EMF in 14 frequency bands,
recorded by an EME Spy 140 (Satimo) exposimeter in the city's administrative
regions, and the incidence of the tumors registered from January 2012 to May
2015. The studied cancer cases have a random spatial distribution inside the
city. On the other hand, and by means of an ecological study, we verified that
the exposure to RF-EMF registered in the city of Albacete shows little
correlation with the incidence of the studied tumors (gliomas (rho=0.15),
meningiomas (rho=0.19) and lymphomas (rho=-0.03)). The proposed methodology
inaugurates an unexplored analysis path in this field.
PMID- 28499232
TI - Co-application of sewage sludge with biochar increases disappearance of
polycyclic aromatic hydrocarbons from fertilized soil in long term field
experiment.
AB - The application of sewage sludge with biochar as fertilizer may be a new method
improves soil properties. Biochar increases of the crops productivity and
reduction of bioavailability of contaminants. In the present study the
persistence of sum of 16 (Sigma16) PAHs (US EPA 16 PAHs) in a sewage sludge
amended soil (11t/h) and in a sewage sludge-amended soil with the addition of
biochar (at a rate of 2.5, 5 or 10% of sewage sludge (dry weight basis)) was
determined. This study was carried out as a plot experiment over a period of
18months. Samples for analysis were taken at the beginning of the study and after
6, 12 and 18months from the beginning of the experiment. Application of sewage
sludge as a soil amendment did not cause a significant change (P>=0.05) in the
soil content of Sigma16 PAHs. In turn, the addition of biochar with sewage sludge
to the soil, regardless of the contribution of biochar in the sewage sludge,
resulted in a significant decrease in PAH content already at the beginning of the
experiment. Throughout the experiment, in all treatments the PAH content varied,
predominantly showing a decreasing trend. Ultimately, after 18months the content
of Sigma16 PAHs decreased by 19% in the experiment with sewage sludge alone and
by 45, 35 and 28% in the experiment with sewage sludge and the 2.5%, 5.0% and 10%
biochar rates, respectively. After 18months of the study, the largest losses in
the sewage sludge-amended soil were observed for 2- and 3-ring PAHs. In the
sewage sludge- and biochar-amended soil, compared to the beginning of the study
and the sewage sludge-amended soil, the highest losses were found for 5- and 6
ring PAHs (2.5 and 5.0% rates) as well as for 5- and 2-ring PAHs (10% rate).
PMID- 28499233
TI - Multi-scale sustainability assessments for biomass-based and coal-based fuels in
China.
AB - Transportation liquid fuels production is heavily depend on oil. In recent years,
developing biomass based and coal based fuels are regarded as promising
alternatives for non-petroleum based fuels in China. With the rapid growth of
constructing and planning b biomass based and coal based fuels production
projects, sustainability assessments are needed to simultaneously consider the
resource, the economic, and the environmental factors. This paper performs multi
scale analyses on the biomass based and coal based fuels in China. The production
cost, life cycle cost, and ecological life cycle cost (ELCC) of these synfuels
are investigated to compare their pros to cons and reveal the sustainability. The
results show that BTL fuels has high production cost. It lacks of economic
attractiveness. However, insignificant resource cost and environmental cost lead
to a substantially lower ELCC, which may indicate better ecological
sustainability. CTL fuels, on the contrary, is lower in production cost and
reliable for economic benefit. But its coal consumption and pollutant emissions
are both serious, leading to overwhelming resource cost and environmental cost. A
shifting from petroleum to CTL fuels could double the ELCC, posing great threat
to the sustainability of the entire fuels industry.
PMID- 28499234
TI - Magnetic implants in the tongue for assistive technologies: Tests of migration;
oromotor function; and tissue response in miniature pigs.
AB - OBJECTIVE: Uncertain biological consequences of titanium-magnet (Ti-mag) tongue
implants constrain application of the Tongue Drive System (TDS), a brain-tongue
computer interface for individuals with severe physical impairment. Here we
describe oromotor function and tongue tissue response following Ti-Mag
implantation and explantation in the miniature pig, an animal model with a tongue
similar in size to humans. DESIGN: A 1.8*6.2mm Ti-mag tracer was implanted into
the anterior tongue in five Yucatan minipigs. X-rays were taken immediately and
>six days after implantation to evaluate tracer migration. In three minipigs, the
tracer was explanted >16days after implantation. Twenty-five days post
explantation, tongue tissue was harvested and processed for histological and
immunohistochemical (IHC) markers of healing. In two minipigs tissue markers of
healing were evaluated post-mortem following >12days implantation. Drink cycle
rate (DCR) was characterized to determine the impact of procedures on oromotor
function. RESULTS: Neither implantation (N=5) nor explantation (N=3) changed DCR.
X-rays revealed minimal tracer migration (N=4, 0-4mm). By histology and IHC a
robust capsule was present two weeks post-implantation with limited fibrosis.
Explantation produced localized fibrosis and limited muscle remodeling.
CONCLUSIONS: These findings suggest the safety of Ti-mag anterior tongue implants
for assistive technologies in humans.
PMID- 28499235
TI - Probiotics: A non-conventional therapy for oral lichen planus.
AB - Oral lichen planus (OLP) is a common T-cell mediated chronic inflammatory
disease. Although the etiology is still unclear, present studies suggest that the
composition of the oral microbiota and psychological problems are implicated in
the etiology of OLP. The pathogenesis of OLP includes mainly antigen-specific and
non-specific mechanisms. Antigen-specific mechanisms involve T-cell activation
following antigen presentation and apoptosis of basal keratinocytes triggered by
CD8+ cytotoxic T cells, while non-specific mechanisms consist of matrix
metalloproteinase over-expression and mast cell degranulation in OLP lesions.
Therapies for OLP are mainly used to control symptoms and a specific cure is not
yet available. Probiotics are capable of modulating the immune response in a
strain-specific manner. They are able to alleviate microbial infection and
suppress T-cell activation, infiltration and proliferation, as well as suppress
keratinocyte apoptosis and nuclear factor-kappa B signaling. Furthermore,
probiotics can also modulate the production of inflammatory cytokines and
microRNAs, inhibit MMP-9 expression and mast cell degranulation, and ameliorate
psychological problems, all of which are involved in the pathogenesis of OLP.
Therefore, we hypothesize that probiotics may be applicable to OLP as a safe,
inexpensive and non-conventional therapy.
PMID- 28499236
TI - Putative periodontal pathogens in the subgingival plaque of Sudanese subjects
with aggressive periodontitis.
AB - BACKGROUND AND OBJECTIVES: There has been limited study of the bacterial species
associated with aggressive periodontitis (AgP) in high-risk populations in
Africa. The aim of this study was to investigate and quantify the presence of
four putative periodontal pathogens in the subgingival plaque of Sudanese
subjects with AgP. A secondary aim was to investigate the effect of varying the
detection threshold on the reported prevalence of the bacterial species
investigated. MATERIALS AND METHODS: Subgingival plaque samples were collected
from AgP cases (n=73) and healthy controls (n=71). Bacterial DNA was extracted
and analyzed by quantitative polymerase chain reaction for the detection and
quantification of four putative periodontal pathogens: Porphyromonas gingivalis,
Aggregatibacter actinomycetemcomitans, Treponema denticola and Tannerella
forsythia. RESULTS: At the lowest detection threshold (>101 cells), P. gingivalis
(p<0.0001) was more prevalent in AgP cases than controls. T. forsythia and T.
denticola had a high prevalence (>70%) in AgP cases at all detection levels.
While T. forsythia was significantly more frequently identified in AgP than in
controls at all detection thresholds, this was only the case for T. denticola at
the intermediate threshold (>102 cells). A. actinomycetemcomitans was identified
less frequently than the other bacterial species with no difference in its
prevalence between AgP cases and controls. CONCLUSION: The prevalence of the
putative periodontal pathogens investigated varied considerably in Sudanese
subjects with AgP and in periodontally healthy controls depending on the
detection thresholds applied. T. forsythia was identified as having the strongest
association with AgP.
PMID- 28499237
TI - The protective effect of propofol against TNF-alpha-induced apoptosis was
mediated via inhibiting iNOS/NO production and maintaining intracellular Ca2+
homeostasis in mouse hippocampal HT22 cells.
AB - AIM: Inflammation cytokine tumor necrosis factor-alpha (TNF-alpha) induces
apoptosis in neuronal cells. We hypothesized that propofol may attenuate TNF
alpha-induced apoptosis in mouse hippocampal HT22 cells and aimed to explore the
underlying mechanisms. METHODS: Mouse hippocampal HT22 cells were pretreated with
propofol, and then stimulated with TNF-alpha. Cell viability was measured by cell
counting kit 8 (CCK8). Cell apoptosis was examined by flow cytometry analysis.
The effect of propofol on TNF-alpha-modulated nitric oxide production was
measured by a nitrate reductase assay kit, intracellular calcium release and
mitochondrial membrane potential (MMP) depolarization were measured by flow
cytometry analysis, and the expression of inducible nitric oxide synthase (iNOS),
C/EBP homologous protein (CHOP), B-cell lymphoma 2 (Bcl2) family and caspases
were detected by Western blot. RESULTS: Compared with control, TNF-alpha
concentration- and time-dependently increased HT22 cell apoptosis, which was
attenuated by 25MUmol/l propofol. TNF-alpha (40ng/ml, 24h) induced the
overexpression of iNOS and the release of nitric oxide, caused the accumulation
of intracellular Ca2+ and endoplasmic reticulum (ER) stress, and therefore
leading to mitochondrial dysfunction. Importantly, these effects were alleviated
by 25MUmol/l propofol. CONCLUSIONS: We demonstrated that propofol could attenuate
TNF-alpha-induced HT22 apoptosis. More importantly, we indicated that the
underlying mechanism may involve iNOS/NO, Ca2+ and mitochondrial dysfunction.
PMID- 28499238
TI - Inhibition of iNOS protects cardiomyocytes against coxsackievirus B3-induced cell
injury by suppressing autophagy.
AB - BACKGROUND: Coxsackievirus B3 (CVB3), a member of the picornavirus family, is one
of the major causative enteroviruses of viral myocarditis. The aim of the current
study was to investigate the role and underlying mechanism of iNOS and autophagy
in CVB3 infected cardiomyocytes. METHODS: Myocardial cell H9c2 were randomly
divided into four groups: control group, CVB3 group, CVB3+L-NAME group and the
CVB3+iNOS siRNA group. Cell proliferation was detected by MTT method and cell
apoptosis was determined by flow cytometric. The protein expression levels were
determined by Western blot. Anisomycin was used to activate JNK pathway in CVB3
infected H9c2 cells. RESULTS: The results demonstrated that the inhibition of
iNOS significantly elevated cell proliferation and suppressed cell apoptosis of
CVB3-induced H9c2 cells. The production of MDA was obviously decreased, while the
activity of SOD was increased by the addition of L-NAME or iNOS siRNA compared
with the CVB3 group. Expression of the autophagy marker proteins LC3 II and
Beclin 1 was significantly decreased, and the autophagy substrate p62 was
dramatically increased in iNOS inhibition groups compared with the CVB3 group.
Moreover, iNOS inhibition suppressed the JNK pathway in CVB3-infected H9c2 cells.
Furthermore, administration of the JNK pathway stimulator, anisomycin,
counteracted the effect of iNOS inhibition in CVB3-infected H9c2 cells.
CONCLUSION: The inhibition of iNOS protects cardiomyocytes against CVB3-induced
cell injury by regulating autophagy and the JNK pathway, which may provide a
novel therapeutic strategy for treating CVB3-induced myocarditis.
PMID- 28499239
TI - Effect of recombinant human endostatin on hypertrophic scar fibroblast apoptosis
in a rabbit ear model.
AB - Hypertrophic scar (HS) is a dermal fibroproliferative disorder characterized by
the excessive proliferation of fibroblasts and is thought to result from a
cellular imbalance caused by the increased growth and reduced apoptosis of
hypertrophic scar fibroblasts (HSFs). Our recent study demonstrated that
recombinant human endostatin (rhEndostatin) plays a key role in the inhibition of
HSF proliferation in vitro, with a resulting decrease in dermal thickness and
scar hypertrophy. However, the effect of this protein on HSF apoptosis is
unknown. The present study was undertaken to directly examine the effect of
rhEndostatin on HSF apoptosis in the rabbit ear model. Transmission electron
microscopy and flow cytometry were used to investigate HSF apoptosis in scar
tissues and cultured HSFs in vitro, respectively. The expression levels of the c
jun, c-fos, NF-kappaB, fas, caspase-3, and bcl-2 gene products in HSFs were
quantified using real-time PCR and Western blotting assays. Our data reveal that
rhEndostatin (2.5 or 5mg/ml) induces HSF apoptotic cell death in scar tissue.
Additionally, HSFs treated with rhEndostatin (100mg/L) in vitro accumulated in
early and late apoptosis and displayed significantly decreased expression of c
jun, c-fos, NF-kappaB, fas, caspase-3 and bcl-2. In sum, these results
demonstrate that rhEndostatin induces HSF apoptosis, and this phenotypeis
partially due to downregulation of NF-kappaB and bcl-2. These findings suggest
that rhEndostatin may have an inhibitory effect on scar hypertrophy in vivo via
HSF apoptotic induction and therefore has potential therapeutic use for the
treatment of HS.
PMID- 28499240
TI - Establishment of a rat model of chronic Prostatitis/Chronic Pelvic Pain Syndrome
(CP/CPPS) induced by immunization with a novel peptide T2.
AB - BACKGROUND: The exact etiological mechanism of Chronic Prostatitis/chronic pelvic
pain syndrome (CP/CPPS) is still unclear however autoimmunity is the most valid
theory. We developed a rat model of Chronic Prostatitis/chronic pelvic pain
syndrome by using a novel peptide (T2) isolated from TRPM8. This model might be
beneficial in elucidating mechanisms involved in the pathogenesis of Chronic
Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS). METHODS: 40 male Sprague
Dawley rats with an average weight of 180-220g were equally distributed into five
groups. The normal control group was injected with normal saline (.9% NACL), the
CFA group with CFA, AL(OH)3 group was given AL(OH)3 injection, T2 group using a
novel peptide T2 and T2+AL(OH)3+CFA group was injected with T2+AL(OH)3+CFA.
Dosing to all rat groups were injected subcutaneously. Hematoxylin and eosin
staining and Immunohistochemistry were used to investigate inflammatory cell
infiltration and IL-1beta in the prostate tissue respectively. ELISA technique
was used to measure the serum level of CRP and TNF-alpha. T-test was used to
analyze the results. RESULTS: Maximum infiltration of inflammatory cells and the
highest level of IL-1beta in the prostate tissue was observed in T2+AL(OH)3+CFA
group as revealed by histopathology and Immunohistochemistry, respectively.
Furthermore, T2+AL(OH)3+CFA group attained the peak value of serum TNF-alpha and
CRP as determined by ELISA technique. CONCLUSION: Our results demonstrated that
T2 in combination with AL(OH)3 and CFA induced severe Prostatitis in rats. We
believe that our present model will be highly beneficial for investigation of the
pathophysiology of Chronic Prostatitis/Chronic Pelvic Pain Syndrome.
PMID- 28499241
TI - Pathophysiology, mechanisms and applications of mesenchymal stem cells for the
treatment of spinal cord injury.
AB - Spinal Cord Injury (SCI) is a serious devastating condition associated to the
high chances of morbidity and mortality. It involves a primary and a secondary
injury, former cause damages to both lower and upper motor neurones and disrupts
sensory, motor and autonomic functions while the latter involves various stages
of molecular plus cellular incidents which elaborate the original injury. In the
treatment of SCI, stem cells possess a good therapeutic potential. Bone marrow,
adipose tissue, placenta, amniotic fluid and umbilical cord are the good sources
for mesenchymal stem cells. This review article shows the uses of bone marrow
derived mesenchymal cells in the treatment of acute and chronic case of SCI and
its future scope.
PMID- 28499242
TI - Potential ameliorative effects of grape seed-derived polyphenols against cadmium
induced prostatic deficits.
AB - Grape (Vitis vinifera) is consumed as fruit and wine for people. In this study,
rat model of prostatic deficits was induced by orally receiving 60mg/L cadmium
chlorine (CdCl2) through drinking water for 20 weeks. Grape seed-derived
polyphenols extract (GSP) was orally given for 20 weeks. Finally, the prostatic
levels of E-cadherin, fibronectin, and alpha-smooth muscle actin were measured by
immunohistochemical and qPCR analysis. The oxidative stress was measured by
detecting the levels of malondialdehyde, nitric oxide, reduced
glutathione/oxidized glutathione and enzymatic antioxidant status. Additionally,
the prostatic expressions of transforming growth factor-beta1 (TGF-beta1), type I
TGF-beta receptor (TGF-betaRI), Smad3, phosphorylation-Smad3 (p-Smad3), Smad7,
nuclear related factor-2 (Nrf-2), heme oxygenase-1 (HO-1) and gamma-glutamate
cysteine ligase catalytic subunit (gamma-GCLC) were measured by western blot. The
levels of microRNA (miR)-133a/b were measured by qPCR. It was observed that GSP
ameliorated the prostatic oxidative stress and fibrosis induced by CdCl2. GSP
also inhibited the over-generation of TGF-beta1 and p-Smad3, as well as enhanced
the levels of Smad7, Nrf-2, HO-1, gamma-GCLC and miR-133a/b. These results showed
that GSP could attenuate Cd-induced prostatic deficits.
PMID- 28499244
TI - MicroRNA-24-1 suppresses mouse hepatoma cell invasion and metastasis via directly
targeting O-GlcNAc transferase.
AB - MicroRNAs (miRNAs) are endogenous non-coding regulatory RNAs involved in multiple
cellular processes. Emerging evidences showed that miRNAs are involved in
changing the cell surface glycosylation modification and oncogenesis. In this
study, the role of miRNA-24-1 in O-GlcNAcylation and metastasis of mouse
hepatocarcinoma cells was investigated. miRNAs expression array profiles were
obtained from mouse hepatocarcinoma cell lines Hca-P and Hca-F with the low/high
lymphatic metastasis potential, respectively. Based on the miRNAs expression
array profiles, miRNA-24-1 expression was found to exhibit converse coincidence
with metastasis potential, O-GlcNAc transferase (OGT) expression and O
GlcNAcylation. Dual-luciferase reporter assay revealed that miRNA-24-1
specifically binds to 3'-UTR of OGT. Furthermore, transfecting mouse
hepatocarcinoma cells with miR-24-1 mimic and antisense oligonucleotide showed
miR-24-mediates OGT expression silencing. This silencing is associated with the
suppression of cell metastasis potential, down-regulation of the O-GlcNAcylation
on c-Myc and decrease of c-Myc expression at the protein level rather than the
mRNA level. Collectively, these results suggested that as a tumor suppressor, miR
24-1 may regulate mouse hepatocarcinoma cells migration and invasion, at least
partially through targeting OGT, which could regulate the O-GlcNAcylation and the
stability of this oncoprotein c-Myc. This may give insight into a novel mechanism
and therapy of tumor lymphatic metastasis.
PMID- 28499243
TI - Diospyros, an under-utilized, multi-purpose plant genus: A review.
AB - The genus Diospyros from family Ebenaceae has versatile uses including edible
fruits, valuable timber, and ornamental uses. The plant parts of numerous species
have been in use as remedies in various folk healing practices, which include
therapy for hemorrhage, incontinence, insomnia, hiccough, diarrhea etc.
Phytochemical constituents such as terpenoids, ursanes, lupanes, polyphenols,
tannins, hydrocarbons, and lipids, benzopyrones, naphthoquinones, oleananes, and
taraxeranes have been isolated from different species of this genus. The
biological activities of these plants such as antioxidant, anti-inflammatory,
analgesic, antipyretic, anti-diabetic, antibacterial, anthelmintic,
antihypertensive, cosmeceutical, enzyme-inhibitory etc. have been validated by
means of an in vitro, in vivo, and clinical tests. As a rich reserve of
pharmacologically important components, this genus can accelerate the pace of
drug discovery. Accordingly, the aim of the present review is to survey and
summarize the recent literature pertaining to the medicinal and pharmacological
uses of Diospyros, and to select experimental evidence on the pharmacological
properties of this genus. In addition, the review also aims at identifying areas
that need development to make use of this genus, especially its fruit and
phytochemicals as means for economic development and for drug discovery.
PMID- 28499245
TI - Anti-hyperalgesic effect of Lippia grata leaf essential oil complexed with beta
cyclodextrin in a chronic musculoskeletal pain animal model: Complemented with a
molecular docking and antioxidant screening.
AB - BACKGROUND: Due to its unclear pathophysiology, the pharmacological treatment of
fibromyalgia is a challenge for researchers. Studies using medicinal plants, such
as those from the genus Lippia, complexed with cyclodextrins (CDs) have shown
innovative results. OBJECTIVE: The present research intended to evaluate the
effect of an inclusion complex containing beta-cyclodextrin (betaCD) inclusion
complex with Lippia grata (LG) essential oil in a chronic musculoskeletal pain
model, its central activity and its possible interaction with neurotransmitters
involved in pain. METHODS: After acid saline-induced chronic muscle pain, male
mice were evaluated for primary and secondary hyperalgesia and muscle strength.
Moreover, an antagonist assay was performed to assess the possible involvement of
the opioidergic, serotonergic and noradrenergic pathways. In addition, Fos
protein in the spinal cord was assessed, and a docking study and antioxidant
assays were performed. RESULTS: The treatment with LG-betaCD, especially in the
dose of 24mg/kg, was able to significantly decrease (p<0.05) the paw withdrawal
and muscle threshold. Furthermore, LG-betaCD was shown to affect the opioidergic
and serotonergic pathways. There were no significant changes in muscle strength.
Fos protein immunofluorescence showed a significant decrease in expression in the
dorsal horn of the spinal cord. The main compounds of LG showed through the
docking study interaction energies with the alpha-adrenergic and MUOpioid
receptors. In all antioxidant assays, LG exhibited stronger antioxidant
activities than LG-betaCD. CONCLUSION: This study suggested that LG-betaCD could
be considered as a valuable source for designing new drugs in the treatment of
chronic pain, especially musculoskeletal pain.
PMID- 28499246
TI - Evaluation of the therapeutic effects of lateral approach combined with
anteromedial approach in the treatment of terrible triad of the elbow.
AB - OBJECTIVE: This study aims to evaluate the therapeutic effects of the lateral
approach combined with anteromedial approach in the treatment of terrible triad
of the elbow. METHODS: Between June 2010 and January 2015, 334 patients suffering
from terrible triad of the elbow, amongst whom 105 cases underwent lateral
approaches combined with anteromedial approaches, 112 cases underwent lateral
approaches, and 117 cases underwent anteromedial approaches were included in the
study. The serum levels of C-reactive protein (CRP), interleukin-6 (IL-6),
interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) were detected
using enzyme-linked immunosorbent assay (ELISA) before operation and at 7 days
and 3 months after operation. X-ray imaging was employed to examine the recovery
condition of the elbow, and the joint motion and the forearm rotation of elbow
were evaluated before and after the operation. RESULTS: Excellent rate was
obtained in accordance with the Mayo Elbow Performance Score (MEPS). The serum
levels of CRP, IL-6, IL-8 and TNF-alpha gradually decreased to normal levels
after the operation, and recovery was faster in patients undergoing lateral
approach combined with anteromedial approach in comparison to those undergoing
lateral and anteromedial approaches. The X-ray images showed good recovery of
elbows in all patients, but the range of joint motion, forearm rotation degree,
and MEPS were higher in patients undergoing lateral approach combined with
anteromedial approach compared to those undergoing lateral and anteromedial
approaches independently. CONCLUSION: Taken together, these findings demonstrate
lateral approach combined with anteromedial approach reveals better therapeutic
effect than lateral approach and anteromedial approach in the treatment of
terrible triad of the elbow.
PMID- 28499247
TI - NLRC5 deficiency promotes myocardial damage induced by high fat diet in mice
through activating TLR4/NF-kappaB.
AB - The metabolic syndrome could be induced by high fat diet, leading to
cardiovascular diseases, such as myocardial damage. Inflammation response and
oxidative stress have been reported to be involved in high fat-induced heart
injury, and the molecular mechanism is not fully understood. The NOD-like protein
family member, NLRC5, could interact with IKKalpha to inhibit IKK complex
activation. In our study, high fat diet-feeding mice showed cardiac fibrosis,
inflammation and oxidative stress through collagen accumulation, TLR4/NF-kappaB
and MAPKs signaling pathways activation. NLRC5 knockout mice fed with high fat
showed accelerated fibrosis and inflammation response by promoting alpha-SMA,
Collagen I, Collagen III, TLR4/MyD88, phosphorylated IKKalpha, IkappaBalpha and
NF-kappaB expression. And no effect on oxidative stress was observed in wild type
and NLRC5-deficiency samples in in vivo studies. Moreover, NLRC5-knockout and
knockdown cardiac muscle cells challenged with LPS also exhibited aggravated
fibrosis levels and inflammatory response without any influences on ROS
production in in vitro studies. In conclusion, the findings indicated that NLRC5
showed important effects on high fat-induced heart injury via fibrosis and
inflammation modulation, providing an essential target for improving myocardial
damage induced by high fat diet.
PMID- 28499248
TI - Influence of fertilisation with sewage sludge-derived preparation on selected
soil properties and prairie cordgrass yield.
AB - The aim of the study was to evaluate the effect of using a fertilizer obtained
from waste substances on selected physical and chemical properties of soil and
biomass yield Spartina pectinate. The fertilizer used for soil (C) fertilisation
contained sewage sludge (SS), waste soil fractions of brown coal (BC), brown coal
ash (BCA) enriched with mineral potassium (K) fertilizer (C+SS+BC+BCA+K). The
composition of the preparation was developed by the authors and adjusted to the
quality of the fertilised soil and the individual characteristics of the plant.
It was assumed that the preparation should replace expensive conventional
fertilisation methods, allow for management of waste substances and improve soil
properties, leading to a high yield of Spartina pectinata used as energy crop.
The plants were grown on the soil from the Huta Czestochowa steelworks effect
zone. The soil was light, with acid reaction (pH KCl =5.5), with small contents
of such contaminants as Cd and Zn and elevated Pb content. Based on a three-year
pot experiment, the paper presents the results of the examinations concerning the
effect of fertilisation on soil pH, hydrolytic acidity, sorptive properties,
content of humic acids, organic coal and total nitrogen in soil and crop
yielding. The effect of the use of the fertilizer (C+SS+BC+BCA+K) was compared
with the use of the sludge (C+SS), sludge with mineral fertilizers (C+SS+NPK),
mixture of brown coal and mineral fertilizers (C+BC+NPK) and effect of only
mineral fertilizers (C+NPK). Fertilisation with (C+SS+BC+BCA+K) led to the
increase in soil pH from 5.5 to 6.0, which is considered sufficient for light
soils. The fertilised soil was characterized by sorption capacity of ca. 5.8
cmol(+)/kg, and, after fertilisation with O+W+P, reached the value of ca. 8.0
cmol(+)kg-1. Consequently the soil can be regarded as of good quality in terms of
its capability to store nutrients. The C:N ratio was also extended from 11:1
(control soil) to 14:1 (C+SS+BC+BCA+K). The yield of Spartina pectinata in the
first year was 1.6 and in the third year 2.7 times higher in the case of
fertilisation with the investigated mixture as compared to the control.
PMID- 28499249
TI - Estimates of potential childhood lead exposure from contaminated soil using the
US EPA IEUBK Model in Sydney, Australia.
AB - Surface soils in portions of the Sydney (New South Wales, Australia) urban area
are contaminated with lead (Pb) primarily from past use of Pb in gasoline, the
deterioration of exterior lead-based paints, and industrial activities. Surface
soil samples (n=341) were collected from a depth of 0-2.5cm at a density of
approximately one sample per square kilometre within the Sydney estuary catchment
and analysed for lead. The bioaccessibility of soil Pb was analysed in 18
samples. The blood lead level (BLL) of a hypothetical 24 month old child was
predicted at soil sampling sites in residential and open land use using the
United States Environmental Protection Agency (US EPA) Integrated Exposure Uptake
and Biokinetic (IEUBK) model. Other environmental exposures used the Australian
National Environmental Protection Measure (NEPM) default values. The IEUBK model
predicted a geometric mean BLL of 2.0+/-2.1ug/dL using measured soil lead
bioavailability measurements (bioavailability =34%) and 2.4+/-2.8ug/dL using the
Australian NEPM default assumption (bioavailability =50%). Assuming children were
present and residing at the sampling locations, the IEUBK model incorporating
soil Pb bioavailability predicted that 5.6% of the children at the sampling
locations could potentially have BLLs exceeding 5ug/dL and 2.1% potentially could
have BLLs exceeding 10ug/dL. These estimations are consistent with BLLs
previously measured in children in Sydney.
PMID- 28499252
TI - Crosstalk between HDAC6 and Nox2-based NADPH oxidase mediates HIV-1 Tat-induced
pro-inflammatory responses in astrocytes.
AB - Histone deacetylase 6 (HDAC6) likely is important in inflammatory diseases.
However, how HDAC6 exerts its effect on inflammatory processes remains unclear.
HIV-1 transactivator of transcription (Tat) activates NADPH oxidase resulting in
generation of reactive oxygen species (ROS), leading to extensive neuro
inflammation in the central nervous system. We investigated the correlation of
HDAC6 and NADPH oxidase in HIV-1 Tat-stimulated astrocytes. HDAC6 knockdown
attenuated HIV-1 Tat-induced ROS generation and NADPH oxidase activation. HDAC6
knockdown suppressed HIV-1 Tat-induced expression of NADPH oxidase subunits, such
as Nox2, p47phox, and p22phox. Specific inhibition of HDAC6 using tubastatin A
suppressed HIV-1 Tat-induced ROS generation and activation of NADPH oxidase. N
acetyl cysteine, diphenyl iodonium, and apocynin suppressed HIV-1 Tat-induced
expression of HDAC6 and the pro-inflammatory chemokines CCL2, CXCL8, and CXCL10.
Nox2 knockdown attenuated HIV-1 Tat-induced HDAC6 expression and subsequent
expression of chemokines. The collective results point to the potential crosstalk
between HDAC6 and NADPH oxidase, which could be a combined therapeutic target for
relief of HIV-1 Tat-mediated neuro-inflammation.
PMID- 28499251
TI - Sequestration of polyunsaturated fatty acids in membrane phospholipids of
Caenorhabditis elegans dauer larva attenuates eicosanoid biosynthesis for
prolonged survival.
AB - Mechanistic basis governing the extreme longevity and developmental quiescence of
dauer juvenile, a "non-ageing" developmental variant of Caenorhabditis elegans,
has remained largely obscure. Using a lipidomic approach comprising multiple
reaction monitoring transitions specific to distinct fatty acyl moieties, we
demonstrated that in comparison to other developmental stages, the membrane
phospholipids of dauer larva contain a unique enrichment of polyunsaturated fatty
acids (PUFAs). Esterified PUFAs in phospholipids exhibited temporal accumulation
throughout the course of dauer endurance, followed by sharp reductions prior to
termination of diapause. Reductions in esterified PUFAs were accompanied by
concomitant increases in unbound PUFAs, as well as their corresponding downstream
oxidized derivatives (i.e. eicosanoids). Global phospholipidomics has unveiled
that PUFA sequestration in membrane phospholipids denotes an essential aspect of
dauer dormancy, principally via suppression of eicosanoid production; and a
failure to upkeep membrane lipid homeostasis is associated with termination of
dauer endurance.
PMID- 28499250
TI - Redox regulation of microRNAs in endometriosis-associated pain.
AB - Endometriosis is a chronic, painful condition with unknown etiology. A
differential expression of microRNAs in the endometriotic tissues from women with
endometriosis with pain compared to those without suggested a plausible role for
miRNA or epigenetic mechanisms in the etiology of endometriotic pain. The
peritoneal milieu is involved in maintenance of endometriotic lesion and
nociception. We recently showed the mechanistic role for oxidized-lipoproteins
(ox-LDLs) present in peritoneal fluid (PF) in endometriosis and pain. We explored
the possibility of ox-LDLs modulating the expression of miRNAs in a manner
similar to PF from women with endometriosis. Expression levels of miRNAs and
their predicted nociceptive and inflammatory targets were determined in PF and ox
LDL treated human endometrial cell-lines. Samples from IRB-approved and consented
patients with and without endometriosis or pain were used. These were compared to
endometrial cell-lines treated with various forms of oxidized-lipoproteins. RNA
(including miRNAs) were isolated from treated endometrial cells and expression
levels were determined using commercial miRNome arrays. Cell lysates were used in
immunoblotting for inflammatory proteins using a protein array. Twenty miRNAs
including isoforms of miR-29, miR-181 and let-7 were mutually differentially
expressed in cells treated with PF from endometriosis patients with pain and
those treated with ox-LDL components. The ox-LDLs and endo-PF treatment also
produced significant overexpression of microRNA predicted target genes nerve
growth factor, interleukin-6 and prostaglandin E synthase and overexpression of
their downstream protein targets Mip1alpha and MCP1. This study showed
similarities between miRNA regulation in PF from endometriotic women and ox-LDLs
present in abundance in the PF of these women. Key miRNAs responsible for
targeting nociceptive and inflammatory molecules were downregulated in the
presence of ox-LDLs and endo-PF, thus playing a role in the etiology of
endometriotic pain. These redox-sensitive miRNAs can be of potential use as
targets in the treatment of endometriosis-associated pain.
PMID- 28499254
TI - Improving xylose utilization of defatted rice bran for nisin production by
overexpression of a xylose transcriptional regulator in Lactococcus lactis.
AB - Present investigation explores the potential of defatted rice bran (DRB) serving
as sole carbon source and partial nitrogen source to support Lactococcus lactis
growth and nisin production. To retain the nutrients in DRB, especially protein
fractions, thermal pretreatment followed by enzymatic hydrolysis without washing
step was applied for saccharification. A maximum of 45.64g reducing sugar mainly
containing 30.26g glucose and 5.66g xylose from 100g DRB was attained in
hydrolysates of DRB (HD). A novel strategy of xylR (xylose transcriptional
regulator) overexpression followed by evolutionary engineering was proposed,
which significantly increased the capacity of L. lactis to metabolize xylose.
Subsequently, RT-PCR results indicated that xylR overexpression stimulated
expression of xylose assimilation genes synergistically with exposure to xylose.
In HD medium, the highest nisin titer of the engineered strain FEXR was
3824.53IU/mL, which was 1.37 times of that in sucrose medium by the original
strain F44.
PMID- 28499253
TI - The role of sodium hydrosulfide in attenuating the aging process via PI3K/AKT and
CaMKKbeta/AMPK pathways.
AB - Age-related dysfunction of the central auditory system, known as central
presbycusis, is characterized by defects in speech perception and sound
localization. It is important to determine the pathogenesis of central
presbycusis in order to explore a feasible and effective intervention method.
Recent work has provided fascinating insight into the beneficial function of H2S
on oxidative stress and stress-related disease. In this study, we investigated
the pathogenesis of central presbycusis and tried to explore the mechanism of H2S
action on different aspects of aging by utilizing a mimetic aging rat and
senescent cellular model. Our results indicate that NaHS decreased oxidative
stress and apoptosis levels in an aging model via CaMKKbeta and PI3K/AKT
signaling pathways. Moreover, we found that NaHS restored the decreased activity
of antioxidants such as GSH, SOD and CAT in the aging model in vivo and in vitro
by regulating CaMKKbeta and PI3K/AKT. Mitochondria function was preserved by
NaHS, as indicated by the following: DNA POLG and OGG-1, the base excision repair
enzymes in mitochondrial, were upregulated; OXPHOS activity was downregulated;
mitochondrial membrane potential was restored; ATP production was increased; and
mtDNA damage, indicated by the common deletion (CD), declined. These effects were
also achieved by activating CaMKKbeta/AMPK and PI3K/AKT signaling pathways.
Lastly, protein homeostasis, indicated by HSP90 alpha, was strengthened by NaHS
via CaMKKbeta and PI3K/AKT. Our findings demonstrate that the ability to resist
oxidative stress and mitochondria function are both decreased as aging developed;
however, NaHS, a novel free radical scavenger and mitochondrial protective agent,
precludes the process of oxidative damage by activating CaMKKbeta and PI3K/AKT.
This study might provide a therapeutic target for aging and age-related disease.
PMID- 28499255
TI - Identification of an aspidospermine derivative from borage extract as an anti
amyloid compound: A possible link between protein aggregation and antimalarial
drugs.
AB - A number of human diseases, including Alzheimer's and Parkinson's have been
linked to amyloid formation. To search for an anti-amyloidogenic product,
alkaloid enriched extract from borage leaves was examined for anti-amyloidogenic
activity using Hen Egg White Lysozyme (HEWL) as a model protein. After isolation
of the plant extract using rHPLC, only one fraction indicated a significant
bioactivity. TEM analysis confirmed a remarkable reduction of amyloid fibrils in
the presence of the bioactive fraction. To identify the effective substance in
the fraction, mass spectrometry, FTIR, and NMR were performed. Our analyses
determined that the bioactive compound as 1-acetyl-19,21-epoxy-15,16
dimethoxyaspidospermidine-17-ol, a derivative of aspidospermine. To investigate
the mechanism of the inhibition, ANS binding, intrinsic fluorescence, and amide I
content were performed in the presence of the bioactive compound. All the results
confirmed the role of the compound in assisting the proper folding of the
protein. In addition, molecular docking indicated the aspidospermine derivative
binds the amyloidogenic region of the protein. Our results show that the alkaloid
extracted from borage leaves reduces protein aggregation mediating through
structural elements of the protein, promoting the correct folding of lysozyme.
Since a number of aspidospermine compounds have been shown to possess potent
antimalarial activities, the action of compound identified in the present study
suggests a possible link between protein aggregation and aspidospermine drugs.
PMID- 28499256
TI - From common to rare Zingiberaceae plants - A metabolomics study using GC-MS.
AB - Zingiberaceae plants, commonly known as gingers, have been popular for their
medicinal and culinary uses since time immemorial. In spite of their numerous
health-promoting applications, many Zingiberaceae plants still receive no
scientific attention. Moreover, existing reports mostly focused only on the
Zingiberaceae rhizomes. Here, untargeted metabolite profiling using Gas
Chromatography - Mass Spectrometry (GC-MS) was used to compare the metabolic
composition of leaves and rhizomes of the more common gingers, Zingiber
officinale Rosc. (ZO), Curcuma longa L. (CL), and Etlingera elatior (Jack) R.M.
Smith (EE), and the rare gingers, Amomum muricarpum Elmer (AM), Etlingera
philippinensis (Ridl.) R.M. Smith (EP), and Hornstedtia conoidea Ridl. (HC).
Principal component analysis (PCA) demonstrated that different species show
substantial chemical differentiation and revealed potential markers among the
different Zingiberaceae plants. Interestingly, the leaves of AM, CL, EE, EP, and
HC had significantly higher levels of chlorogenic acid than ZO. Moreover,
rhizomes of EP and HC were found to contain significantly higher levels of amino
acids than ZO. Sugars and organic acids were generally less abundant in ZO leaves
and rhizomes than in the other gingers. The leaves of EP and rhizomes of AM were
found most similar to the leaves and rhizomes of common gingers, respectively.
Results of this study provide significant baseline information on assessing the
possible usage of the leaves of common gingers and further propagation and
exploration of EP and AM. This study, being the first metabolomics report on rare
plants such as AM, EP and HC, affirms the usefulness of untargeted metabolite
profiling in exploring under-investigated plants.
PMID- 28499257
TI - Distinguishing the cognitive processes of mindfulness: Developing a standardised
mindfulness technique for use in longitudinal randomised control trials.
AB - A capacity model of mindfulness is adopted to differentiate the cognitive faculty
of mindfulness from the metacognitive processes required to cultivate this
faculty in mindfulness training. The model provides an explanatory framework
incorporating both the developmental progression from focussed attention to open
monitoring styles of mindfulness practice, along with the development of
equanimity and insight. A standardised technique for activating these processes
without the addition of secondary components is then introduced. Mindfulness
based interventions currently available for use in randomised control trials
introduce components ancillary to the cognitive processes of mindfulness,
limiting their ability to draw clear causative inferences. The standardised
technique presented here does not introduce such ancillary factors, rendering it
a valuable tool with which to investigate the processes activated in mindfulness
practice.
PMID- 28499258
TI - Trajectories of positive alcohol expectancies and drinking: An examination of
young adults in the US and Sweden.
AB - Positive alcohol expectancies and alcohol use tend to increase from adolescence
to young adulthood, yet little is known about the associations between these
constructs across cultures. The current study adds to the extant literature by
examining the growth trajectories of positive alcohol expectancies and drinking
behavior among United States (US) and Swedish participants during a critical
period where significant change in these outcomes may be expected to occur. A
total of 870 (US, N=362; Sweden, N=508) high school seniors completed baseline, 6
month, and 12-month assessments of alcohol expectancies and drinking (i.e.,
drinks per week). Changes in positive alcohol expectancies and drinking behavior
were examined using a parallel process latent growth model. In both samples,
higher baseline levels of positive alcohol expectancies were associated with a
higher number of drinks consumed per week at baseline. In the US sample, lower
baseline levels of positive alcohol expectancies were associated with a greater
increase in positive alcohol expectancies at 12-month follow-up, and lower
baseline levels of drinks per week were associated with a greater increase in
drinks consumed per week at 12-month follow-up. In the Swedish sample, an
increase in positive alcohol expectancies over time was associated with an
increase in drinks consumed per week over the same period of time. Additional
research is needed to examine when and for whom expectancy-based alcohol
interventions are most efficacious.
PMID- 28499259
TI - Systematic review of social media interventions for smoking cessation.
AB - BACKGROUND: Popular social media could extend the reach of smoking cessation
efforts. In this systematic review, our objectives were: 1) to determine whether
social media interventions for smoking cessation are feasible, acceptable, and
potentially effective; 2) to identify approaches for recruiting subjects; and 3)
to examine the specific intervention design components and strategies employed to
promote user engagement and retention. METHODS: We searched Scopus, Medline,
EMBASE, Cochrane Central, PsychINFO, CINAHL, and Web of Science through July 2016
and reference lists of relevant articles. Included studies described social media
interventions for smoking cessation and must have reported outcomes related to
feasibility, acceptability, usability, or smoking-related outcomes. RESULTS: We
identified 7 studies (all were published since 2014) that enrolled 9755
participants (median=136 [range 40 to 9042]). Studies mainly used Facebook (n=4)
or Twitter (n=2), and emerged as feasible and acceptable. Five studies reported
smoking-related outcomes such as greater abstinence, reduction in relapse, and an
increase in quit attempts. Most studies (n=6) recruited participants using online
or Facebook advertisements. Tailored content, targeted reminders, and moderated
discussions were used to promote participant engagement. Three studies found that
active participation through posting comments or liking content may be associated
with improved outcomes. Retention ranged from 35% to 84% (median=70%) across the
included studies. CONCLUSIONS: Our review highlights the feasibility,
acceptability and preliminary effectiveness of social media interventions for
smoking cessation. Future research should continue to explore approaches for
promoting user engagement and retention, and whether sustained engagement
translates to clinically meaningful smoking cessation outcomes.
PMID- 28499260
TI - Metal toxicity affects predatory stream invertebrates less than other functional
feeding groups.
AB - Ecosystem effects of heavy metals need to be identified for a retrospective risk
assessment, and potential impacts need to be predicted for a prospective risk
assessment. In this study, we established a strong correlation between the toxic
pressure of dissolved metals and invertebrate species. We compiled available data
from a wide geographical range of Australian streams that were contaminated with
heavy metals [mainly copper (Cu) and zinc (Zn)] and the corresponding
invertebrate communities. Heavy metal toxicity is positively related to the
proportion of predators within the invertebrate community, represented by the
predatorratio, with an effect threshold range of 2.6 MUg/L - 26 MUg/L for Cu and
62 MUg/L - 617 MUg/L for Zn. These effect concentrations are in the ranges of the
concentrations identified in model ecosystems and other field investigations and
are just above the existing guideline limits. Heavy metals also affects the taxa
richness negatively. Other community measures, such as the evenness, number of
EPT (Ephemeroptera, Plecoptera, and Trichoptera) taxa, SPEcies At Risk
(SPEAR)pesticides or SPEARsalinity were relatively poorly correlated with heavy
metal toxicity in the streams. Therefore, we suggest applying the predatorratio
within the community as a starting point for an indicator of the dissolved metal
toxicity, the SPEARmetals.
PMID- 28499261
TI - Structural signatures of water-soluble organic aerosols in contrasting
environments in South America and Western Europe.
AB - This study describes and compares the key structural units present in water
soluble organic carbon (WSOC) fraction of atmospheric aerosols collected in
different South American (Colombia - Medellin and Bogota, Peru - Lima, Argentina
Buenos Aires, and Brazil - Rio de Janeiro, Sao Paulo, and Porto Velho, during
moderate (MBB) and intense (IBB) biomass burning) and Western European (Portugal
Aveiro and Lisbon) locations. Proton nuclear magnetic resonance (1H NMR)
spectroscopy was employed to assess the relative distribution of non-exchangeable
proton functional groups in aerosol WSOC of diverse origin, for the first time to
the authors' knowledge in South America. The relative contribution of the proton
functional groups was in the order H-C > H-C-C= > H-C-O > Ar-H, except in Porto
Velho during MBB, Medellin, Bogota, and Buenos Aires, for which the relative
contribution of H-C-O was higher than that of H-C-C=. The 1H NMR source
attribution confirmed differences in aging processes or regional sources between
the two geographic regions, allowing the differentiation between urban combustion
related aerosol and biological particles. The aerosol WSOC in Aveiro, Lisbon, and
Rio de Janeiro during summer are more oxidized than those from the remaining
locations, indicating the predominance of secondary organic aerosols. Fresh
emissions, namely of smoke particles, becomes important during winter in Aveiro
and Sao Paulo, and in Porto Velho during IBB. The biosphere is an important
source altering the chemical composition of aerosol WSOC in South America
locations. The source attribution in Medellin, Bogota, Buenos Aires, and Lima
confirmed the mixed contributions of biological material, secondary formation, as
well as urban and biomass burning emissions. Overall, the information and
knowledge acquired in this study provide important diagnostic tools for future
studies aiming at understanding the water-soluble organic aerosol problem, their
sources and impact at a wider geographic scale.
PMID- 28499262
TI - Fate and O-methylating detoxification of Tetrabromobisphenol A (TBBPA) in two
earthworms (Metaphire guillelmi and Eisenia fetida).
AB - Tetrabromobisphenol A (TBBPA) is the world's most widely used brominated flame
retardant but there is growing concern about its fate and toxicity in terrestrial
organisms. In this study, two ecologically different earthworms, Metaphire
guillelmi and Eisenia fetida, were exposed to soil spiked with 14C-labeled TBBPA
for 21 days. M. guillelmi accumulated more TBBPA than E. fetida, evidenced by a
2.7-fold higher 14C-uptake rate and a 1.3-fold higher biota-soil accumulation
factor. Considerable amounts of bound residues (up to 40% for M. guillelmi and
18% for E. fetida) formed rapidly in the bodies of both earthworms. 14C
accumulated mostly in the gut of M. guillemi and in the skin of E. fetida,
suggesting that its uptake by M. guillelmi was mainly via gut processes whereas
in E. fetida epidermal adsorption predominated. The TBBPA transformation
potential was greater in M. guillelmi than in E. fetida, since only 5% vs. 34% of
extractable 14C remained as the parent compound after 21 days of exposure.
Besides polar metabolites, the major metabolites in both earthworms were TBBPA
mono- and dimethyl ethers (O-methylation products of TBBPA). Acute toxicity
assessments using filter paper and natural soil tests showed that the methylation
metabolites were much less toxic than the parent TBBPA to both earthworms. It
indicated that earthworms used O-methylation to detoxify TBBPA, and M. guillelmi
exhibited the higher detoxification ability than E. fetida. These results imply
that if only the free parent compound TBBPA is measured, not only bioaccumulation
may be underestimated but also its difference between earthworm species may be
misestimated. The species-dependent fate of TBBPA may provide a better indicator
of the differing sensitivities of earthworms to this environmental contaminant.
PMID- 28499263
TI - Effect of fumigation with chloropicrin on soil bacterial communities and genes
encoding key enzymes involved in nitrogen cycling.
AB - Chloropicrin (CP) is a potential alternative for methyl bromide as a soil
fumigant given that the use of methyl bromide has become limited. However, little
is known about how fumigation with CP affects the condition of the soil microbial
community. In this study, 16S rRNA amplicon sequencing and quantitative PCR were
combined to investigate the effect of CP on soil bacterial community. In total,
938,922 effective reads were obtained from 18 samples and clustered into 58,662
operational taxonomic units at a similarity cut-off of 97%. Both approaches
showed that the primary structure of bacterial community in soil did not
significantly change at the phylum level after fumigation, but CP had a
significant impact on the abundance of the bacterial microbiome that was
recovered and identified. Additionally, bacterial community diversity decreased
significantly, and there was a shift in the predominant populations.
Staphylococcus, Actinomadura, Acinetobacter and Streptomyces significantly
decreased in number or disappeared, and Bacteroides, Lachnoclostridium,
Pseudoalteromonas, Colwellia, Idiomarina and Cobetia became the new predominant
populations. In addition, some species associated with biodegradation, such as
Sphingomonas spp. and Rhodococcus spp., significantly increased in number. The
abundance of ammonia-oxidizing archaea (AOA) were significantly inhibited, yet
the abundance of ammonia-oxidizing bacteria (AOB) significantly increased, and
denitrification was significantly promoted. These changes in bacterial flora can
considerably impact soil function and health and lead to negative effects on the
environment surrounding fumigated soils, indicating the need for proactive risk
management. Our study provides useful information for environmental safety
assessments of CP in China.
PMID- 28499265
TI - Nanoagroparticles emerging trends and future prospect in modern agriculture
system.
AB - Increment of technical knowledge has remarkably uplifted logical thinking among
scientific communities to shape the theoretical concepts into near product
oriented research. The concept of nanotechnology has overwhelmed almost all forms
of lives and has traded its applications in myriad fields. Despite rapid
expansion of nanotechnology, sustainable competitions still do exist in the field
of agriculture. In current scenario, agriculture is a manifestation demand to
provide adequate nutrition for relentless growing global population. It is
estimated that nearly one-third of the global crop production is destroyed
annually. The loss owes to various stresses such as pest infestation, microbial
pathogens, weeds, natural calamities, lack of soil fertility and much more. In
order to overcome these limitations, various technological strategies are
implemented but a majority of these have their own repercussions. Hence there is
a scrawling progress on the evaluation of nanoparticles into agriculture sector
which can reform the modern agricultural system. Applications of these
nanomaterials can add tremendous value in the current scenario of a global food
scarcity. Nanotechnology can address the adverse effects posed by the abundant
use of chemical agrochemicals which are reported to cause biomagnification in an
ecosystem. Based on these facts and consideration, present review envisages on
nanoparticles as nanoherbicides, nanopesticides, onsite detection agro-pathogens
and nanoparticles in post harvest management. The review also elucidates on the
importance of nanoparticles in soil fertility, irrigation management and its
influence on improving crop yield. With scanty reports available on
nanotechnology in agriculture system, present review attributes toward developing
nanoagroparticles as the future prospect which can give new facelift for existing
agriculture system.
PMID- 28499264
TI - Initial clonogenic potential of human endothelial progenitor cells is predictive
of their further properties and establishes a functional hierarchy related to
immaturity.
AB - Endothelial progenitor cells (EPCs) generate in vitro Endothelial Colony Forming
Cells (ECFCs) combining features of endothelial and stem/progenitor cells. Their
angiogenic properties confer them a therapeutic potential for treating ischemic
lesions. They may be isolated from umbilical cord blood (CB-ECFCs) or peripheral
adult blood (AB-ECFCs). It is generally accepted that CB-ECFCs are more
clonogenic, proliferative and angiogenic than AB-ECFCs. Nevertheless, only a few
studies have focused on the functional heterogeneity of CB-ECFCs from different
individuals. Moreover, AB-ECFC loss of function is yet to be precisely described.
We have focused on these two issues that are critical for clinical perspectives.
The detailed clonogenic profile of CB-ECFCs and AB-ECFCs was obtained and
revealed a high inter individual heterogeneity and the absence of correlation
with age. Most CB-ECFCs yielded initial colonies and had functional properties
similar to those of AB-ECFCs. Conversely, a high clonogenicity was associated
with an enhanced proliferative and angiogenic potential and stemness gene
overexpression, confirming that immaturity, lost by AB-ECFCs, was a prerequisite
to functionality. We thus demonstrated the importance of selecting CB-ECFCs
according to specific criteria, and we propose using the initial clonogenicity as
a relevant marker of their potential efficacy on vascular repair.
PMID- 28499266
TI - Model-based optimization of parameters for degradation reaction of an
organophosphorus pesticide, paraoxon, using CeO2 nanoparticles in water media.
AB - Degradation and body surface decontamination is vital to prevent the skin
penetration of paraoxon (POX), an organophosphorus pesticide, and victims
poisoning. CeO2 demonstrated a good efficacy for the degradation of POX. The aim
of the study was to develop a model which includes the impact of weight of CeO2,
POX and diluent volumes on the degradation kinetics. The modelling was realized
with rapid and simple experiments carried out in tubes, in aqueous diluent which
contained ions in order to be in accordance with in vitro skin decontamination
conditions. CeO2 had degraded from 5% (in case of 7.5mmol of POX per gram of
CeO2) to 100% (0.002mmol of POX per gram of CeO2) of POX. Different kinetic
models were tested. Using the particle aggregation kinetic model, the simulated
and experimental data were in a good accordance. It highlighted the importance of
particles aggregation due to salts and consistency of the mix on the degradation
efficiency of CeO2. The model worked also really well to predict the degradation
efficiency of CeO2 powders during in vitro skin experiments. However, it did not
correctly forecast with an aqueous decontaminant, containing CeO2.
PMID- 28499267
TI - A novel germline TP53 mutation p.Pro190Arg detected in a patient with lung and
bilateral breast cancers.
AB - PURPOSE: Li-Fraumeni syndrome (LFS) is a rare genetic disease with strong
predispositions to multiple early-onset neoplasms, mostly sarcomas, breast
cancers, brain tumors and adrenocortical carcinomas (LFS core cancers). In most
LFS families the germline mutations of TP53 tumor suppressor gene were found.
Lung cancer does not belong to the core cancers of LFS, however its higher
incidence is observed in families with TP53 mutations. Our aim was to search for
TP53 mutations in female lung cancer patients whose clinico-demographic
characteristics suggested a probable genetic predisposition to the disease.
MATERIALS AND METHODS: The coding region of TP53 from blood DNA was sequenced
using Sanger method. The functioning of detected mutation was tested by
luciferase reporter assay. RESULTS: We found a nucleotide substitution c.569C>G,
p.Pro190Arg, which was not described in the TP53 germline mutation database
(http://p53.iarc.fr/TP53GermlineMutations.aspx). The mutation destroys the
ability of p53 to transactivate BAX promoter and significantly reduces
transactivation potential of p53 toward the promoter of MDM2 gen. CONCLUSION: We
identified novel germline mutation of TP53.
PMID- 28499268
TI - First universal pharmacophore model for hERG1 K+ channel activators: acthER.
AB - The intra-cavitary drug blockade of hERG1 channel has been extensively studied,
both experimentally and theoretically. Structurally diverse ligands inadvertently
block the hERG1 K+ channel currents lead to drug induced Long QT Syndrome (LQTS).
Accordingly, designing either hERG1 channel openers or current activators, with
the potential to target other binding pockets of the channel, has been introduced
as a viable approach in modern anti-arrhythmia drug development. However, reports
and investigations on the molecular mechanisms underlying activators binding to
the hERG1 channel remain sparse and the overall molecular design principles are
largely unknown. Most of the hERG1 activators were discovered during mandatory
screening for hERG1 blockade. To fill this apparent deficit, the first universal
pharmacophore model for hERG1 K+ channel activators was developed using PHASE. 3D
structures of 18 hERG1 K+ channel activators and their corresponding measured
binding affinity values were used in the development of pharmacophore models.
These compounds spanned a range of structurally different chemotypes with
moderate variation in binding affinity. A five sites AAHRR (A, hydrogen-bond
accepting, H, hydrophobic, R, aromatic) pharmacophore model has shown reasonable
high statistical results compared to the other developed more than 1000
hypotheses. This model was used to construct steric and electrostatic contour
maps. The predictive power of the model was tested with 3 external test set
compounds as true unknowns. Finally, the pharmacophore model was combined with
the previously developed receptor-based model of hERG1 K+ channel to develop and
screen novel activators. The results are quite striking and it suggests a greater
future role for pharmacophore modeling and virtual drug screening simulations in
deciphering complex patterns of molecular mechanisms of hERG1 channel openers at
the target sites. The developed model is available upon request and it may serve
as basis for the synthesis of novel therapeutic hERG1 activators.
PMID- 28499269
TI - Identification of novel serotonin reuptake inhibitors targeting central and
allosteric binding sites: A virtual screening and molecular dynamics simulations
study.
AB - The serotonin (5-hydroxytryptamine, 5HT) transporter (SERT) is a member of
neurotransmitter sodium symporter (NSS) family, which maintains neurotransmitter
by reuptaking 5HT into synapses. Decrease in serotonin concentrations in synaptic
clefts have been reported to cause psychological and neurological disorders.
Therefore, inhibition of SERT is a potent strategy for the treatment of related
diseases such as depression. In this study, approximately 260,000 small molecules
from an available chemical database have been virtually screened both at central
and allosteric binding sites of SERT to identify potent novel candidate SERT
inhibitors. A set of docking algorithms were used to predict binding modes and
energies of compounds. Screening analyses led three top-ranked hit compounds
(160234, Otava ID: 7118020138; 159166, Otava ID: 7117171303; and 69419, Otava ID:
118671819) for central binding site (S1) and one compound (93507, Otava ID:
6248262) for allosteric binding site (S2). These promising compounds are then
subjected to long multiple molecular dynamics (MD) simulations to elucidate their
structural and dynamical profiles at the binding cavities of SERT. Higher
predicted binding affinities of identified compounds were also confirmed with
binding free energy calculations (MM/GBSA) in comparison with the reference
central and allosteric binding site inhibitors, paroxetine (8PR) and escitalopram
(68P), respectively. To the best of our knowledge, the present work is the first
structure-based high throughput virtual screening study reported using recently
revealed crystal structure of SERT for screening inhibitors from chemical
databases on S1 and S2 binding sites. Small molecule library screening study
yielded candidate compounds both at central and allosteric binding site of SERT,
and further experimentation may pave the way for developing novel strong
inhibitors.
PMID- 28499270
TI - Simulation studies on structural and thermal properties of alkane thiol capped
gold nanoparticles.
AB - The structural and thermal properties of the passivated gold nanoparticles were
explored employing molecular dynamics simulation for the different surface
coverage densities of the self-assembled monolayer (SAM) of alkane thiol. The
structural properties of the monolayer protected gold nanoparticles such us
overall shape, organization and conformation of the capping alkane thiol chains
were found to be influenced by the capping density. The structural order of the
thiol capped gold nanoparticles enhances with the increase in the surface
coverage density. The specific heat capacity of the alkane thiol capped gold
nanoparticles was found to increase linearly with the thiol coverage density.
This may be attributed to the enhancement in the lattice vibrational energy. The
present simulation results suggest, that the structural and thermal properties of
the alkane thiol capped gold nanoparticles may be modified by the suitable
selection of the SAM coverage density.
PMID- 28499271
TI - Atom and receptor based 3D QSAR models for generating new conformations from
pyrazolopyrimidine as IL-2 inducible tyrosine kinase inhibitors.
AB - In the current study, quantitative three-dimensional structure-activity
relationship (3D-QSAR) method was performed to design a model for new chemical
entities by utilizing pyrazolopyrimidines. Their inhibiting activity on receptor
IL-2 Itk correlates descriptors based on topology and hydrophobicity. The best
model developed by ligand-based (atom-based) approach has correlation-coefficient
of r2: 0.987 and cross-validated squared correlation-coefficient of q2: 0.541
with an external prediction capability of r2: 0.944. Whereas the best selected
model developed by structured-based (receptor-based) approach has correlation
coefficient of r2: 0.987, cross-validated squared correlation-coefficient of q2:
0.637 with an external predictive ability of r2: 0.941. The statistical
parameters prove that structure-based gave a better model to design new chemical
scaffolds. The results achieved indicated that hydrophobicity at R1 location play
a vital role in the inhibitory activity and introduction of appropriately bulky
and strongly hydrophobic-groups at position 3 of the terminal phenyl-group which
is highly significant to enhance the activity. Six new pyrazolopyrimidine
derivatives were designed. Docking simulation study was carried out and their
inhibitory activity was predicted by the best structure based model with
predictive activity of ranging from 8.43 to 8.85 log unit. The interacting
residues PHE435, ASP500, LYS391, GLU436, MET438, CYS442, ILE369, VAL377 of PDB
4HCT were studied with respect to type of bonding with the new compounds. This
study was aimed to search out more potent inhibitors of IL-2 Itk.
PMID- 28499272
TI - Effects of cortisol on the memory bias for emotional words? A study in patients
with depression and healthy participants using the Directed Forgetting task.
AB - Mood congruent alterations in information processing such as an impaired memory
bias for emotional information and impaired inhibitory functions are prominent
features of a major depressive disorder (MDD). Furthermore, in MDD patients
hypothalamic-pituitary-adrenal axis dysfunctions are frequently found. Impairing
effects of stress or cortisol administration on memory retrieval as well as
impairing stress effects on cognitive inhibition are well documented in healthy
participants. In MDD patients, no effect of acute cortisol administration on
memory retrieval was found. The current study investigated the effect of acute
cortisol administration on memory bias in MDD patients (N = 55) and healthy
controls (N = 63) using the Directed Forgetting (DF) task with positive, negative
and neutral words in a placebo controlled, double blind design. After oral
administration of 10 mg hydrocortisone/placebo, the item method of the DF task
was conducted. Memory performance was tested with a free recall test. Cortisol
was not found to have an effect on the results of the DF task. Interestingly,
there was significant impact of valence: both groups showed the highest DF score
for positive words and remembered significantly more positive words that were
supposed to be remembered and significantly more negative words that were
supposed to be forgotten. In general, healthy participants remembered more words
than the depressed patients. Still, the depressed patients were able to inhibit
intentionally irrelevant information at a comparable level as the healthy
controls. These results demonstrate the importance to distinguish in experimental
designs between different cognitive domains such as inhibition and memory in our
study.
PMID- 28499273
TI - Inhibition of NLRP3 inflammasome by thioredoxin-interacting protein in mouse
Kupffer cells as a regulatory mechanism for non-alcoholic fatty liver disease
development.
AB - NOD-like receptor (NLR) NLRP3 inflammasome activation has been implicated in the
progression of non-alcoholic fatty liver disease (NAFLD) from non-alcoholic fatty
liver (NAFL) to non-alcoholic steatohepatitis (NASH). It has been also shown that
palmitic acid (PA) activates NLRP3 inflammasome and promotes interleukin-1beta
(IL-1beta) secretion in Kupffer cells (KCs). However, the specific mechanism of
the NLRP3 inflammasome activation is unclear. We studies the molecular mechanisms
by investigating the roles of Thioredoxin-interacting protein (TXNIP) and NLRP3
on NAFLD development in patients, high-fat diet (HFD)-induced NAFL and methionine
choline deficient (MCD) diet-induced NASH in wild type (WT), TXNIP-/-
(thioredoxin-interacting protein) and NLRP3-/- mice, and isolated KCs. We found
that the expressions of NLRP3 and TXNIP in human liver tissues were higher in
NASH group than in NAFL group. Furthermore, co-immunoprecipitation analyses show
that activation of the TXNIP-NLRP3 inflammasome protein complex occurred in KCs
of NASH WT mice rather than NAFL WT mice, thus suggesting that the formation and
activation of this protein complex is mainly involved in the development of NASH.
NLRP3-/- mice exhibited less severe NASH than WT mice in MCD diet model, whereas
TXNIP deficiency enhanced NLRP3 inflammasome activation and exacerbated liver
injury. PA triggered the activation and co-localization of the NLRP3 inflammasome
protein complex in KCs isolated from WT and TXNIP-/- but not NLRP3-/- mice, and
most of the complex co-localized with mitochondria of KCs following PA
stimulation. Taken together, our novel findings indicate that TXNIP plays a
protective and anti-inflammatory role in the development of NAFLD through binding
and suppressing NLRP3.
PMID- 28499280
TI - Help and Care Seeking for Sexually Transmitted Infections Among Youth in Low- and
Middle-Income Countries.
AB - BACKGROUND: The ability to seek help or medical care for sexually transmitted
infections (STIs) is vital for sexually active youth; yet, their needs are often
unmet. METHODS: We conducted a qualitative systematic review of studies to assess
youth and provider views about the behaviors of young people in help seeking and
care seeking for STI services in low- and middle-income countries. We searched
peer-reviewed literature for studies published between 2001 and 2014 with a study
population of youth (age, 10-24 years) and/or health service providers. Eighteen
studies were identified for inclusion from 18 countries. Thematic analyses
identified key themes across the studies. RESULTS: The majority of studies
included discussion of youth not seeking treatment, resorting to self-treatment,
or waiting to access care, suggesting that many youth still do not seek timely
care for STIs. Youth desired more information on sexual health and cited barriers
related to fear or taboos in obtaining help or information, especially from
providers or parents. Many did not recognize symptoms or waited until symptoms
worsened. However, many youth were able to identify a number of sources for STI
related care including public and private clinics, pharmacies, alternative
healers, and nongovernmental organizations. Youth's help seeking and care seeking
preferences were frequently influenced by desires for confidentiality,
friendliness, and cost. CONCLUSIONS: Youth in low- and middle-income countries
experience significant barriers in help seeking for STIs and often do not seek or
postpone medical care. Improving uptake may require efforts to address clinic
systems, provider attitudes, confidentiality, and cultural norms related to youth
sexuality.
PMID- 28499281
TI - Assortativity and Mixing by Sexual Behaviors and Sociodemographic Characteristics
in Young Adult Heterosexual Dating Partnerships.
AB - BACKGROUND: Assortative sexual mixing, the tendency for individuals to choose
partners with similar characteristics to themselves, may be an important
contributor to the unequal distribution of sexually transmitted infections in
populations. We analyzed the tendency for assortative mixing on demographic and
sexual behaviors characteristics in newly formed young adults dating
partnerships. METHODS: Women aged 18 to 24 years and their male sexual partners
of no more than 6 months were recruited during 2005 to 2010 at universities in
Montreal, Canada. New dating partners were also prospectively recruited during
the 2-year follow-up. We used Spearman and Newman coefficients to examine
correlations between partners' demographic characteristics and sexual behaviors,
and multivariable logistic modeling to determine which characteristics were
assortative. RESULTS: Participants in 502 recruited partnerships were assortative
on age (Spearman P = 0.60), smoking behavior (P = 0.43), ethnicity (Newman
coefficient=0.39), lifetime number of sexual partners (P = 0.36), sex partner
acquisition rates (P = 0.22), gap length between partnerships (P = 0.20), and on
whether they had concurrent partners (P = 0.33). Partners were assortative on
number of lifetime partners, sexual partner acquisition rates, concurrency, and
gap length between partnerships even after adjustment for demographic
characteristics. Reported condom use was correlated between initial and
subsequently recruited partners (P = 0.35). There was little correlation between
the frequencies of vaginal/oral/digital/anal sex between subsequent partnerships.
CONCLUSIONS: Dating partnerships were substantially assortative on various sexual
behaviors as well as demographic characteristics. Though not a representative
population sample, our recruitment of relatively new partnerships reduces
survivor bias inherent to cross-sectional surveys where stable long-term
partnerships are more likely to be sampled.
PMID- 28499282
TI - Can Social Network Analysis Help Address the High Rates of Bacterial Sexually
Transmitted Infections in Saskatchewan?
AB - BACKGROUND: Saskatchewan has one of the highest rates of gonorrhea among the
Canadian provinces-more than double the national rate. In light of these high
rates, and the growing threat of untreatable infections, improved understanding
of gonorrhea transmission dynamics in the province and evaluation of the current
system and tools for disease control are important. METHODS: We extracted data
from a cross-sectional sample of laboratory-confirmed gonorrhea cases between
2003 and 2012 from the notifiable disease files of the Regina Qu'Appelle Health
Region. The database was stratified by calendar year, and social network analysis
combined with statistical modeling was used to identify associations between
measures of connection within the network and the odds of repeat gonorrhea and
risk of coinfection with chlamydia at the time of diagnosis. RESULTS: Networks
were highly fragmented. Younger age and component size were positively associated
with being coinfected with chlamydia. Being coinfected, reporting sex trade
involvement, and component size were all positively associated with repeat
infection. CONCLUSIONS: This is the first study to apply social network analysis
to gonorrhea transmission in Saskatchewan and contributes important information
about the relationship of network connections to gonorrhea/chlamydia coinfection
and repeat gonorrhea. This study also suggests several areas for change of
systems-related factors that could greatly increase understanding of social
networks and enhance the potential for bacterial sexually transmitted infection
control in Saskatchewan.
PMID- 28499283
TI - Chlamydia trachomatis Incidence Using Self-Reports and Serology by Gender, Age
Period, and Sexual Behavior in a Birth Cohort.
AB - BACKGROUND: Although understanding chlamydia incidence assists prevention and
control, analyses based on diagnosed infections may distort the findings.
Therefore, we determined incidence and examined risks in a birth cohort based on
self-reports and serology. METHODS: Self-reported chlamydia and behavior data
were collected from a cohort born in New Zealand in 1972/3 on several occasions
to age 38 years. Sera drawn at ages 26, 32, and 38 years were tested for
antibodies to Chlamydia trachomatis Pgp3 antigen using a recently developed
assay, more sensitive in women (82.9%) than men (54.4%). Chlamydia incidence by
age period (first coitus to age 26, 26-32, and 32-38 years) was calculated
combining self-reports and serostatus and risk factors investigated by Poisson
regression. RESULTS: By age 38 years, 32.7% of women and 20.9% of men had
seroconverted or self-reported a diagnosis. The highest incidence rate was to age
26, 32.7 and 18.4 years per 1000 person-years for women and men, respectively.
Incidence rates increased substantially with increasing number of sexual
partners. After adjusting age period incidence rates for partner numbers, a
relationship with age was not detected until 32 to 38 years, and then only for
women. CONCLUSIONS: Chlamydia was common in this cohort by age 38, despite the
moderate incidence rates by age period. The strongest risk factor for incident
infection was the number of sexual partners. Age, up to 32 years, was not an
independent factor after accounting for partner numbers, and then only for women.
Behavior is more important than age when considering prevention strategies.
PMID- 28499284
TI - Emergence and Spread of Neisseria gonorrhoeae Isolates With Decreased
Susceptibility to Extended-Spectrum Cephalosporins in Argentina, 2009 to 2013.
AB - BACKGROUND: The emergence of Neisseria gonorrhoeae strains with decreased
susceptibility to cephalosporins represents a major concern globally. The aim of
this study was to examine the phenotypic and molecular characteristics of N.
gonorrhoeae isolates with decreased susceptibility to ceftriaxone and cefixime in
Argentina. METHODS: A total of 1987 isolates were collected during 2009 and 2013.
The susceptibility to penicillin G, tetracycline, ciprofloxacin, cefixime,
ceftriaxone, and azithromycin was determined using the agar dilution method. The
major extended-spectrum cephalosporin resistance determinants (penA, mtrR, and
porB1b) were sequenced in 42 N. gonorrhoeae isolates that showed decreased
susceptibility to ceftriaxone (minimum inhibitory concentration [MIC], 0.06-0.125
mg/L) and cefixime (MIC, 0.125-0.25 mg/L). Genotyping by N. gonorrhoeae
multiantigen sequence typing (NG-MAST) was performed. RESULTS: Between 2009 and
2013, there was a shift in the modal MICs for ceftriaxone. Among the 42 isolates
exhibiting decreased susceptibility to ceftriaxone and cefixime, 95.2% were
resistant to penicillin G, 95.2% to tetracycline, 97.6% to ciprofloxacin, and
33.3% to azithromycin. Thirty-five (83.3%) of the 42 isolates had a mosaic penA
allele XXXIV, which has been previously associated with resistance to ceftriaxone
and cefixime as well as treatment failures. The isolates that contained the
mosaic penicillin-binding protein 2 (PBP2) XXXIV were associated with NG-MAST
ST1407 or closely related genotypes. CONCLUSIONS: In Argentina, N. gonorrhoeae
isolates with decreased susceptibility to cefixime and ceftriaxone have now
emerged, mostly due to the introduction of the internationally spread multidrug
resistant NG-MAST ST1407.
PMID- 28499285
TI - Keeping an Eye on Chlamydia and Gonorrhea Conjunctivitis in Infants in the United
States, 2010-2015.
AB - Perinatal transmission of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae
(GC) can result in conjunctivitis in infants. We examined national rates of
reported CT/GC conjunctivitis among infants. Surveillance of these infections is
heavily affected by the completeness of reported data on specimen source and age.
Alternative data sources should be evaluated.
PMID- 28499287
TI - Impact of Eligibility Criteria on Participant Enrollment for a Randomized
Clinical Trial of Gonorrhea Treatment.
AB - BACKGROUND: High rates of failure to qualify for clinical trial participation
increase time and cost required for study completion. Identification of
remediable reasons for prescreen failure can help reduce prescreen failure rates
and improve study cost effectiveness. METHODS: Reasons for prescreen failure to
qualify for participation in a phase 2 randomized clinical trial of treatment of
uncomplicated urogenital gonorrhea were collected from prescreening logs. Reasons
were categorized based on whether the reason was that the subject failed to meet
eligibility criteria or declined participation. Subjects who failed prescreening
but could have been enrolled under protocol amendments were used to estimate
potential cost savings had enrollment completed sooner. RESULTS: Over 88%
(1373/1554) of potential study candidates were not enrolled. The majority (68.8%)
of nonenrolled subjects failed prescreening due to not meeting eligibility
criteria, whereas 31.0% declined to participate. The most common reasons for
failure to qualify were having only nonurogenital gonorrhea (16.4%), limited time
(13.1%), and being on antiretroviral therapy (7.5%). Potential cost savings if
protocol amendments affecting eligibility had been instituted earlier were
estimated at US $127,500. CONCLUSIONS: Careful attention to reasons for prescreen
failure can inform clinical trial protocol development to address trial design
features that may impact successful enrollment. More efficient subject enrollment
can result in substantial cost savings.
PMID- 28499286
TI - Retrospective Review of Gonococcal and Chlamydial Cases of Epididymitis at 2
Canadian Sexually Transmitted Infection Clinics, 2004-2014.
AB - Fifty-seven cases of gonococcal and chlamydial infections complicated by acute
epididymitis seen at 2 Alberta STI clinics from 2004 to 2014 were reviewed. The
majority responded to treatment recommended by national guidelines. Three of 6
treatment failures were not treated according to guidelines.
PMID- 28499288
TI - Impact of Number of Human Papillomavirus Vaccine Doses on Genital Warts Diagnoses
Among a National Cohort of U.S. Adolescents.
AB - BACKGROUND: The impact of fewer than 3 doses of human papillomavirus (HPV)
vaccine on genital warts is uncertain. METHODS: Using the Truven Health Analytics
Marketscan administrative database, we compared rates of genital warts among
women receiving 0, 1, 2, or 3 doses of HPV vaccine. Females aged 9 to 18 years on
January 1, 2007, who were continuously enrolled in the database through December
31, 2013, were included. Patients were assigned an HPV dose state (0, 1, 2, or 3)
based on the last recorded dose. The exposure period began on January 1, 2007, or
the date of the final HPV dose, and lasted until the first diagnosis of genital
warts or December 31, 2013. Multivariable Poisson regression was performed to
determine the risk of genital warts associated with vaccine doses. RESULTS: Among
387,906 subjects, mean age and exposure period were 14.73 and 5.64 years,
respectively. The proportions of doses received were: 52.1%, 7.8%, 9.4%, and
30.7% for 0, 1, 2, and 3 doses, respectively. The rate of genital warts was
1.97/1000 person-years. Receipt of 0 or 1 dose was associated with more genital
warts than 3 doses. The effectiveness of 2 doses following current Centers for
Disease Control and Prevention guidelines was similar to 3 doses. The risk of
genital warts rose with age. CONCLUSIONS: Prevention of genital warts is higher
with completion of 3 vaccine doses than with 1 dose, though 2-dose
recommendations appear to provide similar protection. Prospective effectiveness
studies of recommended 2-dose schedules against clinical endpoints including
persistent infection, genital warts, and cervical dysplasia are necessary to
ensure long-term protection of vaccinated cohorts.
PMID- 28499290
TI - Molecular Typing of Syphilis-Causing Strains Among Human Immunodeficiency Virus
Positive Patients in Antwerp, Belgium.
AB - Centers for Disease Control and Prevention and sequencing-based treponeme typing
was used to analyze 72 blood samples, collected from human immunodeficiency virus
and syphilis co-infected patients during 2014 to 2015 in Antwerp, Belgium. Twenty
nine (40.3%) isolates were polymerase chain reaction positive for Treponema
pallidum, and all tested were macrolide-resistant. Four genotypes were identified
by sequencing-based typing including two new genotypes, U4NR8 and SU9R8, whereas
enhanced Centers for Disease Control and Prevention typing revealed 7 subtypes.
PMID- 28499289
TI - Maternal Syphilis: An Independent Risk Factor for Mother to Infant Human
Immunodeficiency Virus Transmission.
AB - Syphilis is associated with increased human immunodeficiency virus acquisition
and sexual transmission; we examined impact on human immunodeficiency virus
mother-to-child transmission among mother-infant pairs enrolled in the India Six
Week Extended-Dose Nevirapine study. Maternal syphilis, diagnosed serologically
using Venereal Disease Research Laboratory titer plus Treponema Pallidum
Hemagglutination Assay, was associated with 2.5-fold greater risk.
PMID- 28499292
TI - ?
PMID- 28499291
TI - A Survey of 25 North Carolina Health Departments/Districts on Knowledge,
Attitudes, and Current Practices to Seeking Reimbursement From Third-Party Payers
for Sexually Transmitted Disease Services.
AB - BACKGROUND: North Carolina Administrative Code 10A Chapter 41A.0204 (a) states
"local health departments shall provide diagnosis, testing, treatment, follow-up,
and preventive services for syphilis, gonorrhea, chlamydia, ... These services
shall be provided upon request and at no charge to the patient." Although health
departments/districts may bill governmental or nongovernmental insurance
providers for sexually transmitted disease (STD) services, current billing
practices are unknown. Because of its high STD morbidity, the eastern region of
North Carolina was targeted. METHODS: Using a Qualtrics Survey developed to
measure attitudes as well as knowledge and reimbursement practices, this
descriptive study was performed with staff from 25 eastern North Carolina health
departments/districts. Snowball sampling was used to allow for greater inclusion.
Analysis of data was performed at the individual and agency level based on types
of questions in the survey. RESULTS: For knowledge, 87% of the respondents
reported being aware of the possibility of reimbursement from third-party
payers/commercial insurance carriers for STD services. In regard to current
billing of these services, 20 health departments/districts (80%) reported they
were billing these payers. When asked about their attitude of seeking
reimbursement from commercial insurance, 92% reported it was acceptable or very
acceptable. But when asked if STD services should remain a free service at the
health department, 55% supported and 45% did not. CONCLUSIONS: These data provide
a knowledge base for assisting health departments/districts to move forward in
improving STD services as well as maximizing reimbursement from third-party
payers/commercial insurance carriers when possible.
PMID- 28499293
TI - [Current Audiological Diagnostics].
AB - Today's audiological functional diagnostics is based on a stock of hearing tests,
whose large number takes account of the variety of malfunctions of a complex
sensory organ system and the necessity to examine it in a differentiated manner
and at any age of life. The objective is to identify nature and origin of the
hearing loss and to quantify its extent as far as necessary to dispose of the
information needed to initiate the adequate medical (conservative or operational)
treatment or the provision with technical hearing aids or prostheses. Moreover,
audiometry provides the basis for the assessment of impairment and handicap and
for the calculation of the degree of disability. In the present overview, the
current state of the method inventory available for practical use is described,
starting from basic diagnostics over to complex special techniques. The
presentation is systematically grouped in subjective procedures, based on
psychoacoustic exploration, and objective methods, based on physical
measurements: preliminary hearing tests, pure tone threshold, suprathreshold
processing of sound intensity, directional hearing, speech understanding in quiet
and in noise, dichotic hearing, tympanogram, acoustic reflex, otoacoustic
emissions and auditory evoked potentials. Apart from a few still existing gaps,
this method inventory covers the whole spectrum of all clinically relevant
functional deficits of the auditory system.
PMID- 28499294
TI - ?
AB - Hearing loss can be caused by a number of different pathological conditions. Some
of them can be successfully treated, mainly by surgery, depending on the
individual's disease process. However, the treatment of chronic sensorineural
hearing loss with damaged cochlear structures usually needs hearing
rehabilitation by means of technical amplification. During the last 2 decades
tremendous improvements in hearing aid technology led to a higher quality in the
hearing rehabilitation process. For example, due to sophisticated signal
processing the acoustic feedback path could be reduced and hence open fitting
options are available for even more subjects. In particular for high-frequency
hearing loss the use of open fitting is an option. Both the users' acceptance and
the perceived sound quality were significantly increased by open
fittings.However, we are still faced with a low level of readiness in many
hearing impaired subjects to accept acoustic amplification. Since ENT specialists
play a key-role in hearing aid provision, they should promote early hearing aid
rehabilitation and include this in the counselling even in subjects with mild and
moderate hearing loss. Recent investigations demonstrated the benefit of early
hearing aid use in this group of patients since this may help to reduce
subsequent damages as auditory deprivation, social isolation, development of
dementia, and cognitive decline. For subjects with tinnitus, hearing aids may
also support masking by environmental sounds and enhance cortical inhibition.The
present paper describes the latest development of hearing aid technology and the
current state of the art for amplification modalities. Implications for both
hearing aid indication and provision are discussed.
PMID- 28499295
TI - [Tympanoplasty - News And New Perspectives].
AB - Techniques and biomaterials for reconstructive middle ear surgery are under
steady, ongoing development. At the same time, clinical post-surgery results are
evaluated to determine success or failure of the therapy. Routine quality
assessment and assurance is of growing importance in the medical field, and
therefore also in middle ear surgery. The exact definition and acquisition of
outcome parameters is essential for both a comprehensive and detailed quality
assurance. These parameters are not the audiological results alone, but also
additional individual parameters which influence the postoperative outcome after
tympanoplasty. Selection of patients and the preoperative clinical situation, the
extent of the ossicular chain destruction, the chosen reconstruction technique
and material, the audiometric frequency selection and the observational interval
are only some of them. If these parameters are not well documented comparative
analyses between different studies are of limited value. The present overview
aims to describe, compare and evaluate some of the existing assessment and
scoring systems for middle ear surgery. Additionally, new methods for an
intraoperative quality assessment in ossiculoplasty and the postoperative
evaluation of suboptimal hearing results with imaging techniques are available.
In the area of implant development functional elements were integrated in
prostheses to enable not only good sound transmission but also compensation of
occurring atmospheric pressure changes. In combination with other components for
ossicular repair they can be used in a modular manner which, so far show
experimentally and clinically promising results.
PMID- 28499296
TI - [Implantable Hearing Devices].
AB - Combined hearing loss is an essential indication for implantable hearing systems.
Depending on the bone conduction threshold, various options are available:
Patients with mild sensorineural deafness usually benefit from transcutaneous
BCI, while percutaneous BCI systems are recommended also for moderate hearing
loss. For combined hearing loss with moderate and high-grade cochlear hearing
loss, active middle ear implants are recommended. For patients with
incompatibilities or middle ear surgery, implants are a valuable and proven
addition to the therapeutic options.
PMID- 28499297
TI - [Diagnostics and Therapy of Idiopathic Sudden Sensorineural Hearing Loss].
AB - This article reviews recent aspects of diagnostics, differential diagnostics and
evidence in systemic and local therapy of idiopathic, sudden, sensorineural
hearing loss (ISSHL). Since a number of disorders can be accompanied by sudden
hearing loss a meaningful and targeted diagnostic strategy is of utmost
importance. An important differential diagnosis of sudden hearing loss are
intralabyrinthine schwannomas (ILS). The incidence of ILS is probably
significantly underestimated. This may be due to the lack of awareness or lack of
explicit search for an intralabyrinthine tumor on MRI or an inappropriate MRI
technique ('head-MRI' instead of 'temporal bone-MRI' with too high slice
thickness) for the evaluation of sudden hearing loss. Therefore, the request to
the radiologist should specifically include the question for (or exclusion of) an
ILS. With special MRI techniques, it is today possible to visualize an
endolymphatic hydrops. The evidence in the therapy of ISSHL is - with respect to
quality not quantity of studies - unsatisfying. The value of systemically (low
dose) or intratympanically applied corticosteroids in the primary treatment of
ISSHL is still unclear. In order to investigate the efficacy and safety of high
dose corticosteroids in primary treatment for ISSHL a national, multicenter,
three-armed, randomized, triple-blind controlled clinical trial is currently
performed in Germany (http://hodokort-studie.hno.org/). After insufficient
recovery of threshold with systemic therapy of ISSHL, intratympanic
corticosteroid therapy appears to be associated with a significantly higher
chance of improvement of hearing threshold than no therapy or placebo. Both,
hearing gain and final hearing thresholds, however, appear to be independent of
the start of secondary therapy. Based on the currently available data from
clinical studies, no recommendation can be made with respect to type of
corticosteroid and specifics of the intratympanic application protocol.
PMID- 28499298
TI - [Cochlear Implant - State of the Art].
AB - Cochlear implants are the treatment of choice for the auditory rehabilitation of
patients with sensory deafness. They restore the missing function of inner hair
cells by transforming the acoustic signal into electrical stimuli for activation
of auditory nerve fibers. Due to the very fast technology development cochlear
implants provide open-set speech understanding in the majority of patients
including the use of the telephone. Children can achieve a near to normal speech
and language development provided their deafness is detected early after onset
and implantation is performed quickly thereafter. The diagnostic procedure as
well as the surgical techniques have been standardized and can be adapted to the
individual anatomical and physiological needs both in children and adults.
Special cases such as cochlear obliteration or malformations can be addressed.
Device failures and medical complications might require special measures and
reimplantation which can be done in most cases in a straight forward way.
Technology upgrades count for better performance.Future developments will focus
on better electrode nerve interfaces by improving electrode technology. An
increased number of electrical contacts as well as the biological treatment with
regeneration of the dendrides growing onto the electrode will increase the number
of electrical channels. This will give room for improved speech coding strategies
in order to create the bionic ear, i. e. to restore the process of natural
hearing by means of technology. The robot assisted surgery will allow for high
precision surgery and reliable hearing preservation. Biological therapies will
support the bionic ear. Methods are biohybrid electrodes which are coded by stem
cells transplanted into the inner ear to enhance autoproduction of neurotrophins.
Local drug delivery will focus on suppression of trauma reaction and local
regeneration. Gene therapy by nanoparticles will hopefully lead to the
preservation of residual hearing in patients being affected by genetic hearing
loss. Overall the cochlear implant is a very powerful tool to rehabilitate
patients with sensory deafness. More than 1 million of candidates in Germany
today could benefit from this high technology auditory implant. Only 50,000 are
implanted so far. In the future the procedure can be done under local anesthesia,
will be minimal invasive and straight forward. Hearing preservation will be
routine.
PMID- 28499299
TI - [Current Diagnostic Procedures for Diagnosing Vertigo and Dizziness].
AB - Modern diagnostic methods such as video head impulse test and cervical and ocular
vestibular evoked myogenic potentials allow to measure canal and otolith function
quantitatively and objectively. These methods contribute to a complex assessment
of the functional integrity of all 5 sensory elements of the vestibular organ for
the first time. Moreover, in combination with additional vestibular tests
frequency specific and time depended changes of impairments of vestibular sensors
and their pathways can be assessed. Over the past few years, new test methods
have been established step by step in daily clinical diagnostic of vertigo and
dizziness in acute vestibular syndrome and chronic complaints. Modern tests and
concepts caused a paradigm shift in vestibular diagnostic. New classifications of
vestibular disorders and algorithms provide a high diagnostic certainity and
reliability although evidence-based investigations of diagnostic procedures are
still missing.
PMID- 28499300
TI - [Recent surgical options for vestibular vertigo].
AB - Vertigo is not a well defined symptom but a heterogenous entity diagnosed and
treated mainly by otolaryngologists, neurologists, internal medicine and primary
care physicians. Most vertigo syndroms have a good prognosis and management is
predominantly conservative, whereas the need for surgical therapy is rare, but
for a subset of patients often the only remaining option. In this paper, we
describe the development of surgical therapy for hydropic inner ear diseases,
Meniere disease, dehiscence syndroms, perilymphatic fistulas, and benign
paroxysmal vertigo. At the end, we shortly introduce the most recent development
of vestibular implants. Surgical vestibular therapy is still indicated for
selected patients nowadays when conservative options did not reduce symptoms and
patients are still suffering. Success depends on the correct diagnosis and
indication for the different procedures going along with an adequate patient
selection. In regard to the invasiveness and the possible risks due to the
surgery, in depth individual counselling is necessary. Ablative and destructive
surgical procedures usually achieve a successful vertigo control, but go along
with a high risk for hearing loss. Therefore, residual hearing has to be included
in the decission making process for a surgical therapy.
PMID- 28499301
TI - [Validation of the German Version of Tinnitus Functional Index (TFI)].
AB - Tinnitus belongs to seriously debilitating auditory conditions and is often
complicated by comorbidities such as insomnia, difficulties with concentration,
depression, frustration and irritability. To facilitate the grading of symptoms
and the effects of therapeutic strategies, we validated a German-version Tinnitus
Functional Index (TFI) in 229 subjects suffering from chronic tinnitus. Outcome
validity was assessed using the Tinnitus Questionnaire (TQ, German adaptation by
Goebel u. Hiller [1998]). Construct validity was assessed using the "Hamburger
Allgemeine Depressionsskala" (HADS). The German TFI featured excellent internal
consistency (total score Cronbach's alpha=0.93). Factor analysis disclosed eight
TFI subscales as proposed earlier by Meikle et al. [2012]. Intercorrelations were
strong both between the TFI and the TQ (r=0.83), and between the TFI and the HADS
(depression r=0.49, anxiety r=0.51). The German-version TFI qualifies as a rapid
and statistically robust tool for grading the impact of tinnitus on daily living
and for the measurements of therapeutic effects. Regarding depressive
symptomatology, sensitivity of the TFI was comparable to that of the TQ.
PMID- 28499302
TI - [Virtual Planning of Prosthetic Treatment of the Orbit].
AB - Optimal positioning of bone-anchored implants in the treatment of patients with
orbital prosthesis is challenging. The definition of implant axis as well as the
positioning of the implants is important to prevent failures in prosthetic
rehabilitation in these patients. We performed virtual planning of enossal
implants at a base of a standard fan beam CT scan using the software
CoDiagnostiXTM (DentalWings, Montreal, Canada). By 3D-printing a surgical guide
for drilling and implant insertion was manufactured (Med-610TM, Stratasys,
Rehovot, Israel). An orbital exenteration was performed in a patient after
shrinkage of the eyelids 20 years after enucleation and radiation of the orbit
due to rhabdomyosarcoma. 4 Vistafix-3 implants (CochlearTM, Cochlea, Centennial,
USA) were primarily inserted after resection with the help of the 3D-surgical
guide. Prosthetic rehabilitation could be achieved as preplanned to a predictable
result. The individual prosthesis of the orbit showed good functional and
esthetic outcome. The virtual 3D-planning of endosseous implants for prosthetic
orbital and periorbital reconstruction is easy to use and facilitates optimal
placement of implants especially in posttherapeutically altered anatomic
situations.
PMID- 28499303
TI - [Long-term Follow up and patient satisfaction after tympanoplasty with Titanium
Clip-Prothesis].
AB - Aim of the present study is to evaluate the long term results of ossiculoplasty
using titanium clip prosthesis. A retrospective analysis with prospective follow
up has been done including for all patients who had a Clip-PORP implanted between
the years 2002-2013. Following this, audiometric hearing results were measured
with clinical examination including otoscopy and quality of life evaluation using
Glasgow benefit inventory. 48 patients (51 ears, 29 men, 19 women, average age
44.1 years) received followed up after an average duration of 6.3 years. The
overall air-bone-gap (0.5-4 kHz) decreased from 22.8 dB preoperatively to 14.6 dB
postoperatively (p<=0.001). The most frequent indication for surgical treatment
were cholesteatomas and recurrent cholesteatomas (52%), chronic inflammation of
middle ear (12%), revision of radical mastoidectomy (8%) and disturbance in sound
conduction after previous operation (14%). Tympanic membrane was closed in 47
times (92,2%), 4 times (7,8%) there was a defect. Clip-PORP was in situ 39 times
(75%), protrusion and disposal were detected 6 times (11,8%) and 2 times (4%),
respectively. However, 1 time (2%) the prothesis was lost or evaluation was not
possible (3 times, 5,9%). The overall patient satisfaction and general subscale
score after the treatment was beneficially evaluated. There was no change in
social support score nore the physical health score. In summary, the ossicular
chain reconstruction using titan Clip-PORP is safe and well established. Also in
long-term analysis stable hearing results due to reduction of air bone gap are
represented. The subjective quality of life is sustainable improved.
PMID- 28499304
TI - Isolation and Structure Characterization of Cytotoxic Phorbol Esters from the
Seeds of Croton tiglium.
AB - Nine new and eleven known phorbol esters were isolated from an acetone extract of
the seeds of Croton tiglium. Their structures were determined by extensive
analysis of spectroscopic data. Eleven of these compounds were evaluated for
their inhibition activity on human tumor cell lines HL-60 and lung carcinoma
A549. 12-O-Tiglylphorbol-13-acetate (11), 12-O-(2-methyl)-butyrylphorbol-13
aetate (12), and 12-O-tiglylphorbol-13-isobutyrate (13) exhibited strong
inhibition activity against both HL-60 and A549 cell lines with IC50 values <=
0.02 and <= 0.1 ug/mL, respectively. Compound 18 showed strong inhibition
activity against the HL-60 cell line with an IC50 value of 0.02 ug/mL.
PMID- 28499305
TI - Aristolic Acid Derivatives from the Bark of Antidesma ghaesembilla.
AB - Antidesma ghaesembilla is an important medicinal and food plant in many Asian
countries. Ten substances could be isolated from the dichloromethane and methanol
extract: sitostenone (3), daucosterol (4), chavibetol (5), asperphenamate (6),
protocatechuic acid (7), vanillic acid-4-O-beta-D-glucoside (8), 1-O-beta-D
glucopyranosyl-3-O-methyl-phloroglucinol (9), and aristolic acid II-8-O-beta-D
glucoside (10), and two new aristolic acid derivatives, 10-amino-5,7-dimethoxy
aristolic acid II (= 6-amino-9,11-dimethoxyphenanthro[3,4-d]-1,3-dioxole-5
carboxylic acid; 1) and 5,7-dimethoxy-aristolochic acid II (= 9,11-dimethoxy-6
nitrophenantro[3,4-d]-1,3-dioxole-5-carboxylic acid; 2). Exposure to humans of
some of these compounds is associated with a severe disease today known as
aristolochic acid nephropathy. Therefore, the traditional usage of this plant has
to be reconsidered carefully.
PMID- 28499306
TI - How Are Neonatology Fellows Trained for Antenatal Periviability Counseling?
PMID- 28499307
TI - Admission Systolic Blood Pressure and Outcomes in Preterm Infants of <= 26 Weeks'
Gestation.
PMID- 28499308
TI - Outcome of Neonates with Meconium Aspiration Syndrome at the University Hospital
of the West Indies, Jamaica: A Resource-Limited Setting.
PMID- 28499309
TI - Internal Audit of the Canadian Neonatal Network Data Collection System.
PMID- 28499310
TI - Ellagic Acid Administration Negated the Development of Streptozotocin-Induced
Memory Deficit in Rats.
AB - Rampant production of pro-oxidants and inadequate antioxidant availability in
brain exert oxidative stress, which in synergism with impaired glucose metabolism
and inflammation leads to neurodegeneration and cognitive deficits. Ellagic acid
(EGA) is a phenolic compound present in various fruits and is reported to possess
robust antioxidant and anti-inflammatory properties. The present study
investigated the effect of EGA administration on streptozotocin (STZ) induced
dementia in rats. Bilateral intracerebroventricle (ICV) injection of STZ (3
mg/kg) was given to Wistar rats (200 g) on day 1 and 3. EGA (17.5 and 35 mg/kg)
was administered orally to rats for 28 days daily. The spatial memory of rats was
quantified by using Morris water maze and elevated plus maze. Brain TBARS, GSH
and TNF-alpha were also measured. Administration of EGA prevented the induction
of STZ-ICV triggered cognitive deficits as evident by a significant (p<0.05)
reduction in mean escape latency during acquisition trial and increased (p<0.05)
time spent in target quadrant during retrieval trial in Morris water maze test,
and reduction (p<0.05) in transfer latency in elevated plus maze test.
Furthermore, both the doses of EGA attenuated STZ-ICV induced rise in brain TBARS
as well as TNF-alpha and simultaneously enhanced the GSH content. Thus, EGA
ameliorated STZ-induced dementia by probably restoring the balance between
cellular pro-oxidants and anti-oxidants in brain of rats.
PMID- 28499311
TI - Evaluation of Bone Mineral Density in Children with Type I Diabetes Mellitus and
Relationship to Serum Levels of Osteopontin.
AB - Type I diabetes mellitus (T1DM) patients are at risk of osteoporosis and fracture
due to the osteoblast and osteoclast malfunction. Osteopontin (OPN) as the major
non-collagenous bone matrix protein is produced by osteoblasts and osteoclasts
and involve in bone resorption, formation and remodeling. To evaluate the serum
levels of OPN, bone mineral density (BMD) and correlation in patients with T1DM
this study was designed. In this case-control study, 87 children with T1DM and 87
age/sex-matched healthy subjects were enrolled. Blood samples were tested for OPN
levels by ELISA. Dual energy X-ray absorptiometry was used to measure BMD. The
mean levels of BMD in patients was significantly lower than control group
(p<0.0001). There was no significant difference between patients and healthy
subjects regarding the levels of OPN. However, in patients with high levels of
OPN (mean+1.5 standard deviation) the BMD was significantly lower than other
patients (p<0.0001). Totally there was a negative correlation between serum
levels of OPN and BMD in patients with T1DM (p<0.016). These results indicated
that the BMD in T1DM is less than healthy children and elevated level of OPN in
patients could be associated with low BMD. A linear negative correlation between
serum OPN and total BMD of T1DM patients compared to control group was noticed in
this study indicating that the amount of serum OPN could be effective on BMD and
a good predicting factor for osteoporosis in patients.
PMID- 28499312
TI - Evidence for the Involvement of Monoaminergic Pathways in the Antidepressant-Like
Activity of Cymbopogon citratus in Mice.
AB - Objectives Depression is a complex neuropsychiatric disorder, which affects the
quality of life of the sufferers and treatment approach is associated with
serious adverse effects and sometimes therapeutic failures. Cymbopogon citratus
leaf (CC) has been reported to exert anti-depressant effect but its mechanism of
action is yet to be elucidated hence, the need for this study. Methods The anti
depressant-like effect of Cymbopogon citratus aqueous leaf was evaluated using
forced swim test (FST), tail suspension test (TST) and yohimbine-induced
lethality test (YLT) in aggregated mice. Interaction studies involving p
chlorophenylalanine (pCPA), an inhibitor of serotonin biosynthesis and yohimbine,
alpha2-adrenergic receptor antagonist were carried out to evaluate the role of
monoaminergic system in the anti-depressant-like effect of CC. The effect of CC
on spontaneous motor activity (SMA) was also assessed using activity cage.
ResultsCymbopogon citratus (25 and 50 mg/kg, p.o.) demonstrated antidepressant
like activity devoid of significant stimulation of the SMA in mice. However, the
antidepressant-like property of CC was significantly (p<0.05) attenuated by
pretreatment with yohimbine suggesting involvement of noradrenergic pathway in
the action of the extract. Also, pCPA reversed the anti-immobility effect of CC,
indicating the role of serotonergic system in the mediation of its antidepressant
activity. Moreover, CC (25 and 50 mg/kg) potentiated the lethal effect of
yohimbine in aggregated mice, which further suggest the involvement of
monoaminergic systems in its action. Conclusions The results of the study showed
that C. citratus might be interacting with serotonergic and noradrenergic
pathways to mediate its anti-depressant-like effect in mice.
PMID- 28499313
TI - [Changes in Tasks and Job Characteristics in Psychiatric-Psychotherapeutic
Inpatient Treatment in Germany - Description of Relevant Progresses since the
Commencement of the German "Psychiatry Staff Ordinance" in 1990 - Focusing
Psychiatric-Psychotherapeutic Inpatient Intensive Care].
AB - In Germany, mandatory standards in staff job characteristics concerning inpatient
(clinic and day clinic) treatment in psychiatry and psychotherapy were
established for the very first time in the year 1990. Those job characteristics,
concerning the several groups of professionals in German psychiatric
psychotherapeutic hospitals and departments underwent significant changes causing
issues of law, professional and socio-cultural development since then. Besides
general structurally changes, the present article focuses more particularly on
the field of inpatient psychiatric intensive care therapy.
PMID- 28499314
TI - [Small Area Variation in Demographic Aging - Informal and Formal Nursing Care
Ratios and Care Preferences of Senior Citizens Inform Health Care Planners].
AB - Objective Demographic aging affects the number of older individuals potentially
in need of care and age groups of younger individuals potentially providing
formal and informal care. This study examines the current and future demographic
aging and care preferences on a county level in Saxony. Methods To analyze
demographic aging, formal (FISR) and informal intergenerational support ratios
(IISR) based on population data from the Federal Institute for Research on
Building, Urban Affairs and Spatial Development (BBSR) were used. Ratios were
calculated for every county in Saxony from 2012 to 2035. Care preferences for
care settings of senior German citizens in Saxony were determined by a
representative telephone survey (n = 101; 65+). Results FISR and IISR tend to
progress in similar ways and are reduced by 50 % by 2035. Regarding nursing care
preferences, the majority preferred being cared for at home. Implications
Upcoming care ratios may inform community health care planners and decision
makers on critical constellations in advance. Strategies to ensure the future
elderly care are to be developed and implemented.
PMID- 28499315
TI - [Usual Care for Panic Disorder with/without Agoraphobia in Primary Care].
AB - OBJECTIVE: To describe therapy as usual (TAU) for panic disorder with/without
agoraphobia (PDA) in primary care. METHOD: Written survey of 38 general
practitioners (GPs) who provided TAU to 189 patients with PDA as part of an
interventional study. Data were analyzed descriptively. RESULTS: The most common
TAU-interventions were: exploration of psychosocial problems (83 %),
recommendation not to avoid anxiety-provoking stimuli (72 %), prescription of
SSRIs (62 %). Common reasons for referrals were various psychiatric comorbidities
and treatment-refractory anxiety (77 %). GPs rarely used validated diagnostic
tools such as structured interviews (18 %) or questionnaires (14 %). CONCLUSIONS:
TAU mostly involved guideline-recommended psychosocial and pharmacological
interventions. Study-related procedures may limit the generalizability of
findings.
PMID- 28499316
TI - [Diagnostic and Prescription Behavior of General Practitioners and Specialist
Physicians in Patients with Dementia in 2005 and 2015 in Germany].
AB - RESEARCH QUESTION: Did the diagnostic and treatment behavior of general
practitioners and specialists in patients with dementia (PWD) change in Germany
over a period of 11 years (2005 vs. 2015)? METHODS: We performed a retrospective,
database-based evaluation of diagnostic and prescription data from more than 398
general practices (GP) and 50 specialist practices (SP). RESULTS: Compared to
2005, in 2015, the number of PWD had increased by 40.7 % in GP and by 52.4 % in
SP. The proportion of patients with DAT (Alzheimer's Disease) had increased from
45.8 % to 61.7 % in SP. The latter changes are different from those in GP, where
the proportion of patients with DAT had decreased from 20.8 % to 19.2 %. On
average, each individual GP treated 29.9 PWD in 2015 (2005: 21.3), of which 5.9
were DAT patients (2005:4.4), and 1.7 DAT patients received an antidementia drug
(2005: 1.3). On the other hand, an average of 115.4 PWD were diagnosed in SP in
2015 (2005: 75.7), 71.2 of which were DAT patients (2005: 34.7). 54.4 received an
antidementia drug (2005: 23.9). CONCLUSIONS: Improvements in the diagnosis of
dementia and the prescription of antidementia drugs were only found in SP. In
light of their comparatively low potential for change, whether GP will change
their diagnostic and treatment behavior in the future and how SP can be better
integrated into the process of outpatient dementia care remains to be seen.
PMID- 28499317
TI - [Self-Stigma of Depression Scale SSDS - Evaluation of the German Version].
AB - OBJECTIVES: A better understanding of self-stigma facilitates the development and
evaluation of anti-stigma measures. In this study, the Self-Stigma of Depression
Scale (SSDS) is applied for the first time in Germany. The focus lies on
feasibility and psychometric characteristics of the scale. METHODS: Data stem
from a representative population survey in Germany (N = 2,013). The 16 items of
the original SSDS are used to assess anticipated self-stigma in case of
depression. Main component analysis is applied to analyze the factor structure.
RESULTS: The original version of the SDSS could not be replicated in the German
sample. Instead of four, three factors emerged in the German version. They are
similar to three subscales of the original SSDS: "social inadequacy", "help
seeking inhibition" and "self-blame". The internal reliability of the total scale
as well as of the first two subscales is acceptable. CONCLUSION: SSDS is a
multidimensional construct and can serve as an important instrument in research
regarding self-stigma of depression in Germany. A further development of the
German scale is recommended in order to gain greater insight into the nature of
(anticipated) depression self-stigma.
PMID- 28499318
TI - [Psychiatric Inpatient Treatment and Return to Work].
AB - OBJECTIVE: People with mental diseases have a high risk of unemployment and they
have only limited access to the labor market. The return to work is often
associated with fears.The present study aims to provide an overview of the number
of hospitalized psychiatric patients with permanent employment. Moreover it
should give an insight into the process of return to work, the experiences
patients gain and the support they receive. METHODS: In the participating clinics
we measured the number of patients with permanent employment. The main inclusion
criteria for further survey were the status of permanent employment and age
between 18 and 65. The participating patients were interviewed on two occasions,
at the time of inclusion and 3 months after the patient was discharged. The
questions addressed working conditions, job satisfaction and the process of
return-to-work. For statistical analysis, descriptive statistics (frequencies,
means, standard deviations) were used. RESULTS: Only 21 % of n = 815 inpatients
of the participating hospitals were permanently employed. Many patients did not
return to work after being discharged. In many cases the interviewed patients saw
a connection between their job and their current episode of illness. In this
context patients reported unsatisfying workplace conditions such as long working
hours, bad work organization and social conflicts. CONCLUSIONS: For mentally ill
patients, the employment rate in the primary labor market is devastating low.
After psychiatric inpatient treatment patients are at high risk to lose their
jobs. In order to prevent this development, work-related stress factors should be
discussed with inpatients at an early stage and support should be provided during
the return-to-work-process.
PMID- 28499319
TI - [Aftermath of death of a seriously ill family member: Online survey of
psychological distress and care satisfaction of relatives].
AB - Aim of the study The aim of the study was to assess the level of psychosocial
distress and satisfaction with care in family caregivers after the death of a
close relative. Method Anxiety and depression (HADS) of family caregivers were
evaluated in both bereaved family caregivers and a comparable group from the
general population. Furthermore, satisfaction with care (ZUF-8) and social
support (HOPE-Module, ESSI) were assessed after the patients had died. Regression
models were employed to analyze associations between psychological distress and
sociodemographic and care-related variables. Results We conducted an online
survey with 200 bereaved family caregivers (93% female, time since death of the
relative: M=306 days). Of these, 31% were the primary caregiver. The bereaved
caregivers were highly psychologically distressed (high anxiety: 41%/high
depression: 35%). From the survivors' point of view, care at the end of life was
partially insufficient: about one in three of the dying patients had suffered
from pain and 20% had not been treated with dignity. After the relative had
passed away, 44% of the bereaved caregivers did not get information about support
offers; one in three missed emotional assistance. Dissatisfaction with care and
support was associated with increased psychological distress, higher age and a
shorter period of care. Conclusion The high level of psychological distress in
bereaved family caregivers suggests high supportive care needs, which are often
not met in practice. Family caregivers need to be prepared for the time after
their relative's death and should be offered psychosocial support.
PMID- 28499320
TI - [Costs of Medial Care of MRSA Patients at the End-of-Life in a Geriatric Ward].
AB - OBJECTIVE: The present study addresses the financial effects of incidences of
MRSA in the geriatric ward of a German hospital on patients receiving end-of-life
care. The main cost drivers will be identified and the costs calculated.
METHODOLOGY: A retrospective analysis for a period of one year was conducted for
the geriatric ward of a German hospital. In addition to the duration of the
patient's stay and the total costs of his/her case, individual cost categories
such as personnel and material costs were also examined. In order to enable a
cost comparison of MRSA-positive and MRSA-negative patients, matching was used. T
tests were used for purposes of comparison with the case groups. FINDINGS: A
total of 107 cases were included in the study; in 27 of these cases, MRSA was
detected. Patients with MRSA were found to have a longer average stay and to
incur higher average costs. There were no statistically significant differences
in the duration of hospital stay between MRSA-positive and MRSA-negative
patients. Furthermore, no statistically significant differences were seen in the
total costs per case. Significantly higher daily personnel costs for nursing
staff were observed for MRSA-positive patients in the case group of patients with
lower than average total costs. For MRSA-positive patients, these costs amounted
to ? 97.18, while MRSA-negative patients incurred ? 80.44 in costs. Costs of
doctors, medical technicians and non-medical personnel and material costs for
infrastructure showed an opposite tendency. If the case groups for different
total costs are not considered, no significant differences between MRSA-positive
and MRSA-negative patients were found for the individual cost categories
examined. CONCLUSIONS: Although we demonstrated that MRSA-positive patients had
longer stays and caused higher overall costs in the geriatric ward, we did not
find any statistically significant differences between MRSA-positive and MRSA
negative patients. One of the main cost drivers in the care of MRSA-positive
patients was identified as the daily personnel costs for nursing staff. Analysing
processes related to patients' nursing care can be the first step in attempts to
make care for MRSA-positive patients more effective and efficient.
PMID- 28499321
TI - [Group Discussions in Health Services Research - Part 1: Introduction and
Deliberations on Selection of Method and Planning].
AB - Health services researchers focus on the players, structures and impact of health
care in "real life". They investigate how social aspects, financing,
organizational structures, technologies and personal attitudes affect the process
and outcomes of health care. Qualitative research methods are used here, which
address how people act according to their unique living conditions (outside the
context of experimental studies). Different methods of debriefing groups are
essential for qualitative health services research. In 2 subsequent articles, we
aim to outline the diverse facets and possible range of implementation of the
above-mentioned methods, in order to highlight the potential of debriefing groups
in health services research (focus groups or group discussions) using these
methods. In the current article, we would like to encourage researchers to
reflect on relevant topics such as the selection of an appropriate method, the
planning and undertaking of investigations including sampling methods, and
questions regarding ethics and privacy. A follow-up article (in preparation) will
deal with theoretical considerations of the term "group", as well as with the
process of moderating discussions, methods of analyzing data and (qualitative)
online research.
PMID- 28499322
TI - Azathioprine allows glucocorticoid withdrawal - post hoc results of a prospective
study in patients with inflammatory bowel diseases.
AB - Background Azathioprine is recommended as first-line immunosuppressant in
patients with steroid-dependent inflammatory bowel diseases (IBDs). However, data
on steroid withdrawal after induction therapy in IBD patients are sparse. Methods
In this post-hoc analysis of a prospective multicenter study, we analyzed the
proportion and clinical characteristics of 324 azathioprine-tolerant patients as
to whether they could terminate the glucocorticoid therapy after initiation of
treatment with azathioprine. Results Systemic steroid therapy was required in 190
patients (58.6 %) at baseline and in 40 patients (12.3 %) at the end of the
follow-up period (p < 0.001). The median daily dose was 30 mg at baseline and 10
mg at follow-up. At baseline, only 122 patients (37.2 %) were advised to take at
least the lowest recommended dose of 2 mg/kg per day. At follow-up, 221 patients
(68.2 %) were prescribed at least the recommended maintenance dosage. Conclusion
The majority of patients with thiopurine-naive IBDs that needed systemic steroids
at baseline were able to discontinue steroids after 3 - 6 months of azathioprine
therapy. These data support the continued high value of azathioprine in the
immunosuppressive therapy of IBD.
PMID- 28499323
TI - [CMV associated acute liver failure in a patient receiving tocilizumab for
systemic lupus erythematosus].
AB - A 41-year-old female patient was admitted because of febrile jaundice and acute
liver failure. The quick and the bilirubin were 21 % and 258 umol/l, and there
was hepatic encephalopathy I degrees . AST and AP had a maximum of 612 and 215
U/l. Despite a strong left shift in the differential, the CRP had a maximum of 15
mg/l. Because of an atypically presenting systemic lupus erythematosus, she had
been treated with Azathioprine, steroids and Tocilizumab until 12 days before
admission. The diagnostic workup revealed CMV hepatitis and necrotizing
hepatopathy, which was interpreted as toxic hepatitis. At the time of liver
biopsy, on day 3 after admission, staining for Ki-67 indicated strong
regenerative activity in the liver. Treatment with Valgancyclovir, antibiotics
and steroids led to early recovery from liver failure. The case differs from the
few described cases of severe acute liver injury related to Tocilizumab.
Apparently, the combined immunosuppression (steroid, Azathioprine and
Tocilizumab) led to acute liver failure secondary to CMV hepatitis and acute
toxic hepatitis, which may have been aggravated by transiently impaired liver
regeneration. On the other hand, stimulated liver regeneration was proven by
histology despite previous IL6 blockage by Tocilizumab.
PMID- 28499324
TI - Ascariasis imaging: pictorial essay.
AB - Ascariasis is not widespread in Europe, and the knowledge on how to diagnose and
treat the disease is limited to some specialists. On the other hand, clinicians
are facing an increasing number of immigrants from high-prevalence countries and
are, therefore, challenged to update in this field of infectious diseases. Here
we present current knowledge on this infection in 2 parts. The first part
discusses clinical features and hot topics in ascariasis, and the second part
presents imaging features of ascariasis as a pictorial essay.
PMID- 28499325
TI - ?
PMID- 28499326
TI - ?
PMID- 28499327
TI - Impact of polyethyleneglycol addition on diffusion coefficients in binary ionic
liquid electrolytes composed of dicationic ionic liquid and polyethyleneglycol.
AB - We conduct a comparative study of conductivity and diffusion coefficient of two
dicationic ionic liquids (3,3'-(octane-1,8-diyl)bis(1-ethyl-3-imidazolium)
bis(trifluoromethylsulfonyl)amide ([IMCI][TFSI], S1) and 3,3'-(2,2'-(ethane-1,2
diylbis(oxy))bis(ethane-2,1-diyl))bis(1-ethyl-3-imidazolium)
bis(trifluoromethylsulfonyl)amide ([IMOI][TFSI], S2)) at various temperatures.
The diffusion coefficients of cation and anion in ionic liquids are determined by
using pulse gradient spin-echo nuclear magnetic resonance method. S2 shows lower
viscosity, higher conductivity, and higher diffusion coefficient than those of
S1. Moreover, the influence of polyethyleneglycol (PEG200, Mw = 200) addition in
PEG200/IL binary solutions is investigated. PEG200/S1 binary solutions show lower
viscosity, higher conductivity, and higher diffusion coefficient than those of
neat S1. The experimental molar conductivity (Lambda) of neat IL and PEG200/IL
binary solutions is lower than that of the calculated molar conductivity
(LambdaNMR ) from pulse gradient spin-echo nuclear magnetic resonance method at
various temperatures, indicating that not all the diffusion species belong to the
ionic conduction. In other words, NMR diffusion measurements comprise charged and
paired (without charge) ions. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28499328
TI - Negative psychological consequences of breast cancer among recently diagnosed
ethnically diverse women.
AB - OBJECTIVE: Breast cancer has psychological consequences that impact quality of
life. We examined factors associated with negative psychological consequences of
a breast cancer diagnosis, in a diverse sample of 910 recently diagnosed patients
(378 African American, 372 white, and 160 Latina). METHODS: Patients completed an
in-person interview as part of the Breast Cancer Care in Chicago study within an
average of 4 months from diagnosis. The Cockburn negative psychological
consequences of breast cancer screening scale was revised to focus on a breast
cancer diagnosis. Path analysis assessed predictors of psychological consequences
and potential mediators between race/ethnicity and psychological consequences.
RESULTS: Compared to white counterparts, bivariate analysis showed African
American (beta = 1.4, P < .05) and Latina (beta = 3.6, P < .001) women reported
greater psychological consequences. Strongest predictors (P < .05 for all)
included unmet social support (beta = .38), and provider trust (beta = .12),
followed by stage at diagnosis (beta = .10) and perceived neighborhood social
disorder (beta = .09).The strongest mediator between race/ethnicity and
psychological consequences was unmet social support. CONCLUSIONS: African
American and Latina women reported greater psychological consequences related to
their breast cancer diagnosis; this disparity was mediated by differences in
unmet social support. Social support represents a promising point of
intervention.
PMID- 28499329
TI - Effect of Biologic Therapy on Clinical and Laboratory Features of Macrophage
Activation Syndrome Associated With Systemic Juvenile Idiopathic Arthritis.
AB - OBJECTIVE: To assess performance of the 2016 macrophage activation syndrome (MAS)
classification criteria for patients with systemic juvenile idiopathic arthritis
(JIA) who develop MAS while treated with biologic medications. METHODS: A
systematic literature review was performed to identify patients with MAS while
being treated with interleukin (IL)-1 and IL-6 blocking agents. Clinical and
laboratory information was compared to a large previously compiled historical
cohort. RESULTS: Eighteen publications were identified, and after removing
duplicates, 35 patients treated with canakinumab and 49 patients with tocilizumab
were available for analysis; 5 anakinra-treated patients were excluded due to
limited numbers. MAS classification criteria were less likely to classify
tocilizumab-treated patients as having MAS compared to the historical cohort or
canakinumab-treated patients (56.7%, 78.5%, and 84%, respectively; P < 0.01).
Patients who developed MAS while treated with canakinumab trended towards lower
ferritin at MAS onset than the historical cohort (4,050 versus 5,353 ng/ml; P =
0.18) but had no differences in other cardinal clinical or laboratory features.
In comparison, patients who developed MAS while treated with tocilizumab were
less likely febrile and had notably lower ferritin levels (1,152 versus 5,353
ng/ml; P < 0.001). Other features of MAS were more pronounced in patients treated
with tocilizumab, including lower platelet counts, lower fibrinogen, and higher
aspartate aminotransferase levels. Mortality rates for patients with MAS treated
with tocilizumab or canakinumab were not significantly different from the
historical cohort. CONCLUSION: These findings show substantial alterations in MAS
features that may limit utility of defined criteria for diagnosis of systemic JIA
patients treated with biologic agents.
PMID- 28499330
TI - Ascertaining the impact of public rapid transit system on spread of dengue in
urban settings.
AB - Urbanization is an important factor contributing to the global spread of dengue
in recent decades, especially in tropical regions. However, the impact of public
transportation system on local spread of dengue in urban settings remains poorly
understood, due to the difficulty in collecting relevant locality, transportation
and disease incidence data with sufficient detail, and in suitably quantifying
the combined effect of proximity and passenger flow. We quantify proximity and
passenger traffic data relating to 2014-2015 dengue outbreaks in Kaohsiung,
Taiwan by introducing a "Risk Associated with Metro Passengers Presence" (RAMPP),
which considers the passenger traffic of stations located within a fixed radius,
giving more weight to the busier and/or closer stations. In order to analyze the
contagion risk associated with nearby presence of one or more Kaohsiung Rapid
Transit (KRT) stations, we cluster the Li's (the fourth level administrative
subdivision in Taiwan) of Kaohsiung based on their RAMPP value using the K-means
algorithm. We then perform analysis of variance on distinct clusterings and
detect significant differences for both years. The subsequent post hoc tests
(Dunn) show that yearly incidence rate observed in the areas with highest RAMPP
values is always significantly greater than that recorded with smaller RAMPP
values. RAMPP takes into account of population mobility in urban settings via the
use of passenger traffic information of urban transportation system, that
captures the simple but important idea that large amount of passenger flow in and
out of a station can dramatically increase the contagion risk of dengue in the
neighborhood. Our study provides a new perspective in identifying high-risk areas
for transmissions and thus enhances our understanding of how public rapid transit
system contributes to disease spread in densely populated urban areas, which
could be useful in the design of more effective and timely intervention and
control measures for future outbreaks.
PMID- 28499331
TI - Correction: Suppression of CD300A inhibits the growth of diffuse large B-cell
lymphoma.
PMID- 28499332
TI - Correction: LGR5 regulates pro-survival MEK/ERK and proliferative Wnt/beta
catenin signalling in neuroblastoma.
PMID- 28499333
TI - Electrochemical Behavior and Electrodeposition of Nanostructured Rhodium from Low
Temperature Carbamide and Acetamide Containing Melts.
AB - The electrochemical behavior of rhodium at low-temperature carbamide-chloride and
acetamide-chloride melts was investigated. It was found that, during rhodium
anodic dissolution in carbamide and acetamide containing chloride melts, mixed
complexes [Rh(NH3)4Cl2]+ of quasi-octahedral symmetry D4h are produced. The
composition and structure of nascent complex ions have been studied. During
electrochemical reduction of [Rh(NH3)4Cl2]+ complexes, the synthesis of Rh
nanoparticles, as well as Fe, Cu, and Mo nanocoatings, were realized.
PMID- 28499335
TI - Thermal Molding of Organic Thin-Film Transistor Arrays on Curved Surfaces.
AB - In this work, a thermal molding technique is proposed for the fabrication of
plastic electronics on curved surfaces, enabling the preparation of plastic films
with freely designed shapes. The induced strain distribution observed in
poly(ethylene naphthalate) films when planar sheets were deformed into
hemispherical surfaces clearly indicated that natural thermal contraction played
an important role in the formation of the curved surface. A fingertip-shaped
organic thin-film transistor array molded from a real human finger was
fabricated, and slight deformation induced by touching an object was detected
from the drain current response. This type of device will lead to the development
of robot fingers equipped with a sensitive tactile sense for precision work such
as palpation or surgery.
PMID- 28499334
TI - Recent Advances on Neuromorphic Systems Using Phase-Change Materials.
AB - Realization of brain-like computer has always been human's ultimate dream. Today,
the possibility of having this dream come true has been significantly boosted due
to the advent of several emerging non-volatile memory devices. Within these
innovative technologies, phase-change memory device has been commonly regarded as
the most promising candidate to imitate the biological brain, owing to its
excellent scalability, fast switching speed, and low energy consumption. In this
context, a detailed review concerning the physical principles of the neuromorphic
circuit using phase-change materials as well as a comprehensive introduction of
the currently available phase-change neuromorphic prototypes becomes imperative
for scientists to continuously progress the technology of artificial neural
networks. In this paper, we first present the biological mechanism of human
brain, followed by a brief discussion about physical properties of phase-change
materials that recently receive a widespread application on non-volatile memory
field. We then survey recent research on different types of neuromorphic circuits
using phase-change materials in terms of their respective geometrical
architecture and physical schemes to reproduce the biological events of human
brain, in particular for spike-time-dependent plasticity. The relevant virtues
and limitations of these devices are also evaluated. Finally, the future prospect
of the neuromorphic circuit based on phase-change technologies is envisioned.
PMID- 28499336
TI - Optical Properties of Gold Nanoparticle Assemblies on a Glass Surface.
AB - The assemblies of cross-linked gold nanoparticles (AuNP) attract lot of
scientific attention due to feasible perspectives of their use for development of
scaled contact electrodes. Here, we developed and tested method of solid-state
formation of dimers created from small AuNP (~18 nm) cross-linked with 1.9
nonadithiol (NDT) molecules. The morphology of created coating of a glass surface
and its optical-polarization properties have been studied in detail by
combination of scanning electron microscopy, atomic force microscopy, UV-visible
spectroscopy, and modulation-polarization spectroscopy.The modification of
localized surface plasmon resonance (LSPR) of single AuNP and their assemblies
were studied by measuring of the spectral characteristics of polarization
difference at all stages of synthesis. The radiative and nonradiative modes of
LSPR have been analyzed in detail at different angles of incidence light. This
allowed establishing relation between surface morphology of the coating and its
optical properties.
PMID- 28499337
TI - Optically Encoded Semiconducting Polymer Dots with Single-Wavelength Excitation
for Barcoding and Tracking of Single Cells.
AB - Multiplexed optical encoding is emerging as a powerful technique for high
throughput cellular analysis and molecular assays. Most of the developed optical
barcodes, however, either suffer from large particle size or are incompatible
with most commercial optical instruments. Here, a new type of nanoscale
fluorescent barcode (Pdot barcodes) was prepared from semiconducting polymers.
The Pdot barcodes possess the merits of small size (~20 nm in diameter), narrow
emission bands (full-width-at-half-maximum (fwhm) of 30-40 nm), three-color
emissions (blue, green, and red) under single-wavelength excitation, a high
brightness, good pH and thermal stability, and efficient cellular uptake. The
Pdot barcodes were prepared using a three-color and six-intensity encoding
strategy; for ratiometric readout of the barcodes, one of the colors might be
used as an internal reference. We used the Pdot barcodes to label 20 sets of
cancer cells and then distinguished and identified each set based on the Pdot
barcodes using flow cytometry. We also monitored and tracked single cells labeled
with different Pdot barcodes, even through rounds of cell division. These results
suggest Pdot barcodes are strong candidates for discriminating different labeled
cell and for long-term cell tracking.
PMID- 28499338
TI - Hyaluronic Acid Molecular Weight-Dependent Modulation of Mucin Nanostructure for
Potential Mucosal Therapeutic Applications.
AB - This study investigates the effects of different molecular weight hyaluronic
acids (HAs) on the mucosal nanostructure using a pig stomach mucin hydrogel as a
mucosal barrier model. Microparticles (1.0 MUm) and nanoparticles (200 nm) were
used as probes, and their movement in mucin was studied by a three-dimensional
confocal microscopy-based particle tracking technique and by Nanoparticle
Tracking Analysis (NTA) after addition of high-molecular weight (900 kDa) and low
molecular weight (33 kDa) HA. This demonstrated a molecular weight-dependent HA
modulation of the mucin nanostructure with a 2.5-fold decrease in the mobility of
200 nm nanoparticles. To further investigate these mechanisms and to verify that
the natural viscoelastic properties of mucus are not undesirably altered,
rheological measurements were performed on mucin hydrogels with or without HA.
This suggested the observed particle mobility restriction was not attributed to
alterations of the natural mucin cohesive and viscoelastic properties but,
instead, indicates that the added high-molecular weight HA primarily modulates
the mucin nanostructure and mesh size. This study, hereby, demonstrates how mucus
nanostructure can be modulated by the addition of high-molecular weight HA that
offers an opportunity to control mucosal pathogenesis and drug delivery.
PMID- 28499339
TI - Synthetic Applications and Mechanistic Studies of the Hydroxide-Mediated Cleavage
of Carbon-Carbon Bonds in Ketones.
AB - The hydroxide-mediated cleavage of ketones into alkanes and carboxylic acids has
been reinvestigated and the substrate scope extended to benzyl carbonyl
compounds. The transformation is performed with a 0.05 M ketone solution in
refluxing xylene in the presence of 10 equiv of potassium hydroxide. The reaction
constitutes a straightforward protocol for the synthesis of certain phenyl
substituted carboxylic acids from 2-phenylcycloalkanones. The mechanism was
investigated by kinetic experiments which indicated a first order reaction in
hydroxide and a full negative charge in the rate-determining step. The studies
were complemented by a theoretical investigation where two possible pathways were
characterized by DFT/M06-2X. The calculations showed that the scission takes
place by nucleophilic attack of hydroxide on the ketone followed by fragmentation
of the resulting oxyanion into the carboxylic acid and a benzyl anion.
PMID- 28499340
TI - Tebuconazole and Azoxystrobin Residue Behaviors and Distribution in Field and
Cooked Peanut.
AB - Residue behaviors of tebuconazole and azoxystrobin in field condition and the
variation of their residue levels during the boiling process were evaluated. The
terminal residues of peanut kernels were determined by using a modified QuEChERS
method (quick, easy, cheap, effective, rugged, and safe) by means of the
optimization of the novel purification procedure with multiwalled carbon
nanotubes (MWCNTs) and Fe3O4-magnetic nanoparticle (Fe3O4-MNP) in the presence of
an external magnetic field, and the terminal residues were all at trace level at
harvest time. The residues in shells were detected as well to investigate the
distribution in peanuts. Tebuconazole and azoxystrobin residue levels varied
before/after boiling in kernels and shells to different degrees due to various
factors, such as the modes of action and physicochemical properties of
pesticides. The residues have been transferred from peanut into the infusion
during boiling with the higher percentage of azoxystrobin as its lower logKow.
The processing factors (PFs) for tebuconazole and azoxystrobin after processing
were <1, indicating that home cooking in this study could reduce the residue
levels in peanut. Risk assessment showed there was no health risk for consumers.
PMID- 28499341
TI - Positive Detection of GPCR Antagonists Using a System for Inverted Expression of
a Fluorescent Reporter Gene.
AB - The yeast Saccharomyces cerevisiae is a useful eukaryotic host organism for
studying GPCRs as monomolecular models. Fluorescent reporter gene assays for
GPCRs provide a convenient assay for measuring receptor activity using
fluorometric instruments. Generally, these assays detect receptor activation by
agonistic ligands as the induction of fluorescent reporter expression, whereas
antagonistic activities are detected by competition with agonistic ligands,
resulting in decreases in fluorescence intensity. In the current study, we
established a system for inverted expression of a fluorescent reporter by
incorporating a PEST-tag and finding out a promoter inhibited by activation of
the GPCR signaling pathway from yeast endogenous promoters. Because agonists
prevent fluorescent reporter expression in this system, antagonists compete with
agonists and yield increased fluorescence intensity. We used the yeast endogenous
pheromone receptor as a model GPCR to demonstrate the feasibility of our system
for positive detection targeted at antagonists. Compared to results when only
agonists were added to yeast cells, more than 10-fold higher fluorescence
intensity was observed when antagonists were added in combination with agonists.
The approach described here has the potential to markedly accelerate the
identification of GPCR antagonists by providing rapid and straightforward
responses.
PMID- 28499342
TI - Dementia and the privilege of growing old.
PMID- 28499343
TI - Knee Loading Deficits During Dynamic Tasks in Individuals Following Anterior
Cruciate Ligament Reconstruction.
AB - Study Design Controlled laboratory study, cross-sectional. Background Well
documented deficits in sagittal plane knee loading during dynamic tasks indicate
that individuals limit the magnitude of knee loading following anterior cruciate
ligament reconstruction (ACLR). It is unknown how these individuals modulate the
speed of knee flexion during loading, which is particularly important as they
progress to running during rehabilitation. Objective To investigate how
individuals following ACLR perform dynamic knee loading tasks compared to healthy
controls. Methods Two groups of recreationally active individuals participated:
15 healthy controls and 15 individuals post-ACLR (ACLR group). Participants
performed 3 trials of overground running and a single-limb loading (SLL) task.
Sagittal plane range of motion, peak knee extensor moment, peak knee flexion
angular velocity, peak knee power absorption, and rate of knee extensor moment
were calculated during deceleration. A mixed-factor multivariate analysis of
variance was performed to compare differences in variables between groups (ACLR
and control), limbs (within ACLR), and tasks (within control). Results Knee power
absorption, knee flexion angular velocity, and rate of knee extensor moment were
lower in reconstructed limbs (for the SLL task: 5.6 W/kg, 325.8 degrees /s, and
10.5 Nm/kg/s, respectively; for running: 11.8 W/kg, 421.4 degrees /s, and 38.2
Nm/kg/s, respectively) compared to nonsurgical limbs (for the SLL task: 9.7 W/kg,
432.0 degrees /s, and 19.1 Nm/kg/s, respectively; for running: 18.8 W/kg, 494.1
degrees /s, and 72.8 Nm/kg/s, respectively) during both tasks (P<.001). The
magnitudes of between-limb differences in knee flexion angular velocity were
similar in both tasks. Conclusion Despite lower loading demands during SLL,
individuals post-ACLR exhibit deficits in knee dynamics during SLL and running,
suggesting an inability or reluctance to dynamically accommodate forces at the
knee when progressing to running in rehabilitation. J Orthop Sports Phys Ther
2017;47(6):411-419. doi:10.2519/jospt.2017.6912.
PMID- 28499344
TI - The Responsiveness and Minimal Important Change of the Western Ontario Shoulder
Instability Index and Oxford Shoulder Instability Score.
AB - Study Design Prospective cohort study. Background Patient-reported outcome
measurements (PROMs) are widely used to evaluate functional limitations.
Considering PROMs for shoulder instability, information is lacking with regard to
what constitutes a relevant change from baseline scores. Objectives To evaluate
the responsiveness of the Western Ontario Shoulder Instability Index (WOSI) and
the Oxford Shoulder Instability Score (OSIS) and estimate their minimal important
change (MIC). Methods One hundred five consecutive patients with shoulder
instability completed 5 PROMs at baseline and at 6-month follow-up. The PROMs
included the WOSI and OSIS, the Simple Shoulder Test, the Oxford Shoulder Score,
and the Disabilities of the Arm, Shoulder and Hand assessment. Patients also
rated their functional change on an anchor question at follow-up. Responsiveness
was evaluated by testing 9 hypotheses regarding predefined correlations between
the changes in PROM scores, by calculating the area under the receiver operating
characteristic curve and by calculating the standardized response mean and effect
size statistics. The MIC was determined by identifying the optimal cutoff on the
receiver operating characteristic curve. Results Seven out of 9 hypotheses (78%)
were confirmed; as expected, a high correlation (0.77) was found between change
scores of the WOSI and OSIS, whereas the correlations of the change scores of the
WOSI and OSIS with those of general shoulder PROMs were slightly lower (0.61
0.75). The area under the curve was 0.83 (95% confidence interval: 0.75, 0.91)
for the OSIS and 0.82 (95% confidence interval: 0.74, 0.90) for the WOSI. The MIC
was about 6 points for the OSIS and about 14 points for the WOSI. Conclusion Both
the WOSI and OSIS are able to measure change in shoulder function in patients
with shoulder instability. The estimated MIC is 6 points for the OSIS (on a scale
from 0 to 48) and 14 points for the WOSI (on a scale from 0 to 100). J Orthop
Sports Phys Ther 2017;47(6):402-410. doi:10.2519/jospt.2017.6548.
PMID- 28499345
TI - Exploring the genetic architecture and improving genomic prediction accuracy for
mastitis and milk production traits in dairy cattle by mapping variants to
hepatic transcriptomic regions responsive to intra-mammary infection.
AB - BACKGROUND: A better understanding of the genetic architecture of complex traits
can contribute to improve genomic prediction. We hypothesized that genomic
variants associated with mastitis and milk production traits in dairy cattle are
enriched in hepatic transcriptomic regions that are responsive to intra-mammary
infection (IMI). Genomic markers [e.g. single nucleotide polymorphisms (SNPs)]
from those regions, if included, may improve the predictive ability of a genomic
model. RESULTS: We applied a genomic feature best linear unbiased prediction
model (GFBLUP) to implement the above strategy by considering the hepatic
transcriptomic regions responsive to IMI as genomic features. GFBLUP, an
extension of GBLUP, includes a separate genomic effect of SNPs within a genomic
feature, and allows differential weighting of the individual marker relationships
in the prediction equation. Since GFBLUP is computationally intensive, we
investigated whether a SNP set test could be a computationally fast way to
preselect predictive genomic features. The SNP set test assesses the association
between a genomic feature and a trait based on single-SNP genome-wide association
studies. We applied these two approaches to mastitis and milk production traits
(milk, fat and protein yield) in Holstein (HOL, n = 5056) and Jersey (JER, n =
1231) cattle. We observed that a majority of genomic features were enriched in
genomic variants that were associated with mastitis and milk production traits.
Compared to GBLUP, the accuracy of genomic prediction with GFBLUP was marginally
improved (3.2 to 3.9%) in within-breed prediction. The highest increase (164.4%)
in prediction accuracy was observed in across-breed prediction. The significance
of genomic features based on the SNP set test were correlated with changes in
prediction accuracy of GFBLUP (P < 0.05). CONCLUSIONS: GFBLUP provides a
framework for integrating multiple layers of biological knowledge to provide
novel insights into the biological basis of complex traits, and to improve the
accuracy of genomic prediction. The SNP set test might be used as a first-step to
improve GFBLUP models. Approaches like GFBLUP and SNP set test will become
increasingly useful, as the functional annotations of genomes keep accumulating
for a range of species and traits.
PMID- 28499346
TI - Occupational burnout and empathy influence blood pressure control in primary care
physicians.
AB - BACKGROUND: Good physician-patient communication can favor the adoption of
healthy lifestyle habits, which is essential in high blood pressure (BP)
management. More empathic physicians tend to have lower burnout and better
communication skills. We analyzed the association between burnout and empathy
among primary care physicians and nurses and investigated the influence on BP
control performance. METHODS: Descriptive study conducted in 2014 investigating
burnout and empathy levels in 267 primary care physicians and nurses and BP
control data for 301,657 patients under their care. We administered the Maslach
Burnout Inventory and the Jefferson Scale of Physician Empathy and defined good
BP control as a systolic BP <130 mmHg. RESULTS: Low burnout and high empathy were
observed in 58.8% and 33.7% of practitioners, respectively. Burnout and empathy
were significantly negatively associated (p < 0.009). Practitioners with high
empathy and low burnout had significantly better BP control and performance than
those with low empathy and high burnout (p < 0.05). CONCLUSIONS: Low burnout and
high empathy were significantly associated with improved BP control and
performance, possibly in relation to better physician/nurse-patient
communication.
PMID- 28499347
TI - The dynamics of early-state transcriptional changes and aggregate formation in a
Huntington's disease cell model.
AB - BACKGROUND: Huntington's disease (HD) is a fatal neurodegenerative disorder
caused by a CAG expansion in the Huntingtin (HTT) gene. Proteolytic cleavage of
mutant huntingtin (Htt) protein with an expanded polyglutamine (polyQ) stretch
results in production of Htt fragments that aggregate and induce impaired
ubiquitin proteasome, mitochondrial functioning and transcriptional
dysregulation. To understand the time-resolved relationship between aggregate
formation and transcriptional changes at early disease stages, we performed
temporal transcriptome profiling and quantification of aggregate formation in
living cells in an inducible HD cell model. RESULTS: Rat pheochromocytoma (PC12)
cells containing a stably integrated, doxycycline-inducible, eGFP-tagged N
terminal human Htt fragment with an expanded polyQ domain were used to analyse
gene expression changes at different stages of mutant Htt aggregation. At
earliest time points after doxycycline induction no detectable aggregates and few
changes in gene expression were observed. Aggregates started to appear at
intermediate time points. Aggregate formation and subsequent enlargement of
aggregates coincided with a rapid increase in the number of differentially
expressed (DE) genes. The increase in number of large aggregates coincided with a
decrease in the number of smaller aggregates whereas the transcription profile
reverted towards the profile observed before mutant Htt induction. Cluster-based
analysis of the 2,176 differentially expressed genes revealed fourteen distinct
clusters responding differently over time. Functional enrichment analysis of the
two major gene clusters revealed that genes in the up-regulated cluster were
mainly involved in metabolic (antioxidant activity and cellular ketone metabolic
processes) and genes in the down-regulated cluster in developmental processes,
respectively. Promoter-based analysis of the identified gene clusters resulted in
identification of a transcription factor network of which several previously have
been linked to HD. CONCLUSIONS: We demonstrate a time-resolved relationship
between Htt aggregation and changes in the transcriptional profile. We identified
two major gene clusters showing involvement of (i) mitochondrial dysfunction and
(ii) developmental processes implying cellular homeostasis defects. We identified
novel and known HD-linked transcription factors and show their interaction with
known and predicted regulatory proteins. Our data provide a novel resource for
hypothesis building on the role of transcriptional key regulators in early stages
of HD and possibly other polyQ-dependent diseases.
PMID- 28499348
TI - Total delay in treatment among tuberculous meningitis patients in China: a
retrospective cohort study.
AB - BACKGROUND: Currently, there is limited data on the risk factors associated with
treatment delay in tuberculous meningitis (TBM). This study aimed to assess the
duration of delay in the treatment TBM and to investigate its determinants.
METHODS: During the period from September 2009 to February 2016, a retrospective
cohort study of consecutive TBM patients admitted to our hospital was conducted
to determine the risk factors associated with treatment delay in TBM. Treatment
delay duration was defined as the time interval from onset of symptoms (by
patient recall) to initiation of treatment and was stratified into two
categories: <= 20 days, >20 days (median delay day is 20 days). Data collected
included demography, comorbidity, cerebrospinal fluid (CSF) examinations and
others. Univariable and multivariable logistic regression analysis was used to
evaluate the determinants of treatment delay. RESULTS: A total of 161 TBM
patients were included in our study, all were confirmed by CSF mycobacterial
culture. The median treatment delay for all patients included in the study was 20
days [interquartile range, 14-60 days]. Multivariate analysis revealed that age
(<=21 years old, OR = 0.202, 95% CI: 0.079, 0.521), fever (OR = 0.414, 95% CI:
0.180, 0.952), and headache (OR = 0.204, 95% CI: 0.095, 0.442) had significantly
lower risk for treatment delay, while multiple healthcare contact (>3 times) (OR
= 3.938, 95% CI: 1.326, 11.691) as well as CSF chloride (>111 mmol/L) (OR =
2.479, 95% CI: 1.143, 5.377) had significantly higher risk of the delay.
CONCLUSIONS: Our findings indicate that multiple healthcare contact and high CSF
chloride predict the risk of long delay, while young age, fever and headache are
associated with short delay. Maintained focus on awareness of TBM in the
population and in healthcare systems, and continuous implementation of diagnostic
methods for TBM to detect the disease early, may reduce the mortality and
morbidity.
PMID- 28499349
TI - Epimetheus - a multi-profile normalizer for epigenomic sequencing data.
AB - BACKGROUND: Exponentially increasing numbers of NGS-based epigenomic datasets in
public repositories like GEO constitute an enormous source of information that is
invaluable for integrative and comparative studies of gene regulatory mechanisms.
One of today's challenges for such studies is to identify functionally
informative local and global patterns of chromatin states in order to describe
the regulatory impact of the epigenome in normal cell physiology and in case of
pathological aberrations. Critically, the most preferred Chromatin
ImmunoPrecipitation-Sequencing (ChIP-Seq) is inherently prone to significant
variability between assays, which poses significant challenge on comparative
studies. One challenge concerns data normalization to adjust sequencing depth
variation. RESULTS: Currently existing tools either apply linear scaling
corrections and/or are restricted to specific genomic regions, which can be prone
to biases. To overcome these restrictions without any external biases, we
developed Epimetheus, a genome-wide quantile-based multi-profile normalization
tool for histone modification data and related datasets. CONCLUSIONS: Epimetheus
has been successfully used to normalize epigenomics data in previous studies on X
inactivation in breast cancer and in integrative studies of neuronal cell fate
acquisition and tumorigenic transformation; Epimetheus is freely available to the
scientific community.
PMID- 28499351
TI - Prediction of the reliability of genomic breeding values for crossbred
performance.
AB - BACKGROUND: In crossbreeding programs, various genomic prediction models have
been proposed for using phenotypic records of crossbred animals to increase the
selection response for crossbred performance in purebred animals. A possible
model is a model that assumes identical single nucleotide polymorphism (SNP)
effects for the crossbred performance trait across breeds (ASGM). Another model
is a genomic model that assumes breed-specific effects of SNP alleles (BSAM) for
crossbred performance. The aim of this study was to derive and validate equations
for predicting the reliability of estimated genomic breeding values for crossbred
performance in both these models. Prediction equations were derived for
situations when all (phenotyping and) genotyping data have already been
collected, i.e. based on the genetic evaluation model, and for situations when
all genotyping data are not yet available, i.e. when designing breeding programs.
RESULTS: When all genotyping data are available, prediction equations are based
on selection index theory. Without availability of all genotyping data,
prediction equations are based on population parameters (e.g., heritability of
the traits involved, genetic correlation between purebred and crossbred
performance, effective number of chromosome segments). Validation of the
equations for predicting the reliability of genomic breeding values without all
genotyping data was performed based on simulated data of a two-way crossbreeding
program, using either two closely-related breeds, or two unrelated breeds, to
produce crossbred animals. The proposed equations can be used for an easy
comparison of the reliability of genomic estimated breeding values across many
scenarios, especially if all genotyping data are available. We show that BSAM
outperforms ASGM for a specific breed, if the effective number of chromosome
segments that originate from this breed and are shared by selection candidates of
this breed and crossbred reference animals is less than half the effective number
of all chromosome segments that are independently segregating in the same
animals. CONCLUSIONS: The derived equations can be used to predict the
reliability of genomic estimated breeding values for crossbred performance using
ASGM or BSAM in many scenarios, and are thus useful to optimize the design of
breeding programs. Scenarios can vary in terms of the genetic correlation between
purebred and crossbred performances, heritabilities, number of reference animals,
or distance between breeds.
PMID- 28499350
TI - Transcription factor-associated combinatorial epigenetic pattern reveals higher
transcriptional activity of TCF7L2-regulated intragenic enhancers.
AB - BACKGROUND: Recent studies have suggested that combinations of multiple
epigenetic modifications are essential for controlling gene expression. Despite
numerous computational approaches have been developed to decipher the
combinatorial epigenetic patterns or "epigenetic code", none of them has
explicitly addressed the relationship between a specific transcription factor
(TF) and the patterns. METHODS: Here, we developed a novel computational method,
T-cep, for annotating chromatin states associated with a specific TF. T-cep is
composed of three key consecutive modules: (i) Data preprocessing, (ii) HMM
training, and (iii) Potential TF-states calling. RESULTS: We evaluated T-cep on a
TCF7L2-omics data. Unexpectedly, our method has uncovered a novel set of TCF7L2
regulated intragenic enhancers missed by other software tools, where the
associated genes exert the highest gene expression. We further used siRNA
knockdown, Co-transfection, RT-qPCR and Luciferase Reporter Assay not only to
validate the accuracy and efficiency of prediction by T-cep, but also to confirm
the functionality of TCF7L2-regulated enhancers in both MCF7 and PANC1 cells
respectively. CONCLUSIONS: Our study for the first time at a genome-wide scale
reveals the enhanced transcriptional activity of cell-type-specific TCF7L2
intragenic enhancers in regulating gene expression.
PMID- 28499352
TI - Novel optimum contribution selection methods accounting for conflicting
objectives in breeding programs for livestock breeds with historical migration.
AB - BACKGROUND: Optimum contribution selection (OCS) is effective for increasing
genetic gain, controlling the rate of inbreeding and enables maintenance of
genetic diversity. However, this diversity may be caused by high migrant
contributions (MC) in the population due to introgression of genetic material
from other breeds, which can threaten the conservation of small local
populations. Therefore, breeding objectives should not only focus on increasing
genetic gains but also on maintaining genetic originality and diversity of native
alleles. This study aimed at investigating whether OCS was improved by including
MC and modified kinships that account for breed origin of alleles. Three
objective functions were considered for minimizing kinship, minimizing MC and
maximizing genetic gain in the offspring generation, and we investigated their
effects on German Angler and Vorderwald cattle. RESULTS: In most scenarios, the
results were similar for Angler and Vorderwald cattle. A significant positive
correlation between MC and estimated breeding values of the selection candidates
was observed for both breeds, thus traditional OCS would increase MC.
Optimization was performed under the condition that the rate of inbreeding did
not exceed 1% and at least 30% of the maximum progress was achieved for all other
criteria. Although traditional OCS provided the highest breeding values under
restriction of classical kinship, the magnitude of MC in the progeny generation
was not controlled. When MC were constrained or minimized, the kinship at native
alleles increased compared to the reference scenario. Thus, in addition to
constraining MC, constraining kinship at native alleles is required to ensure
that native genetic diversity is maintained. When kinship at native alleles was
constrained, the classical kinship was automatically lowered in most cases and
more sires were selected. However, the average breeding value in the next
generation was also lower than that obtained with traditional OCS. CONCLUSIONS:
For local breeds with historical introgressions, current breeding programs should
focus on increasing genetic gain and controlling inbreeding, as well as
maintaining the genetic originality of the breeds and the diversity of native
alleles via the inclusion of MC and kinship at native alleles in the OCS process.
PMID- 28499353
TI - Transposon insertion sequencing reveals T4SS as the major genetic trait for
conjugation transfer of multi-drug resistance pEIB202 from Edwardsiella.
AB - BACKGROUND: Conjugation is a major type of horizontal transmission of genes that
involves transfer of a plasmid into a recipient using specific conjugation
machinery, which results in an extended spectrum of bacterial antibiotics
resistance. However, there is inadequate knowledge about the regulator and
mechanisms that control the conjugation processes, especially in an aquaculture
environment where a cocktail of antibiotics may be present. Here, we investigated
these with pEIB202, a typical multi-drug resistant IncP plasmid encoding
tetracycline, streptomycin, sulfonamide and chloramphenicol resistance in fish
pathogen Edwardsiella piscicida strain EIB202. RESULTS: We used transposon
insertion sequencing (TIS) to identify genes that are responsible for conjugation
transfer of pEIB202. All ten of the plasmid-borne type IV secretion system (T4SS)
genes and a putative lipoprotein p007 were identified to play an important role
in pEIB202 horizontal transfer. Antibiotics appear to modulate conjugation
frequencies by repressing T4SS gene expression. In addition, we identified topA
gene, which encodes topoisomerase I, as an inhibitor of pEIB202 transfer.
Furthermore, the RNA-seq analysis of the response regulator EsrB encoded on the
chromosome also revealed its essential role in facilitating the conjugation by
upregulating the T4SS genes. CONCLUSIONS: Collectively, our screens unraveled the
genetic basis of the conjugation transfer of pEIB202 and the influence of
horizontally acquired EsrB on this process. Our results will improve the
understanding of the mechanism of plasmid conjugation processes that facilitate
dissemination of antibiotic resistance especially in aquaculture industries.
PMID- 28499354
TI - Patient and care characteristics of self-referrals treated by the general
practitioner cooperative at emergency-care-access-points in the Netherlands.
AB - BACKGROUND: In the Netherlands, out-of-hours primary care is provided in general
practitioner-cooperatives (GPCs). These are increasingly located on site and in
collaboration with emergency departments of hospitals (ED). At such sites, also
called emergency-care-access-points (ECAP), the GPC is generally responsible for
the triage and treatment of self-referrals who used to attend the ED. To evaluate
the effects and safety of this novel organisation, we studied the characteristics
and the quality of care given by GPCs to self-referrals at ECAPs. METHODS:
Retrospective analysis (August 2011-January 2012) of 783 records of self-referred
patients at three Dutch GPCs in an ECAP. This was supplemented with a
retrospective analysis of patient records during a follow-up period of three
months to asses safety. RESULTS: Patient-characteristics: 59% was male, 46% aged
between 16-45 years and 59% trauma-related. Most cases (95%) were triaged low
urgent. None received the highest urgency-category. Quality: The triage outcome
was correct in 79%, underestimated in 12% and overestimated in 9%. After GP
consultation 20% were referred to the ED, mostly for radio-diagnostics. Of the
referrals to secondary care, 98% were according to common medical practice.
Thirty percent had a follow-up contact, mostly with their own general
practitioner, seldom with the ED. Complications, all non-severe, were registered
in 3.2%; 0.4% were possibly preventable. CONCLUSIONS: Self-referred patients at
an ECAP are mostly trauma related, low-urgent and male patients. The majority
could be treated by the GPC without subsequent referral to the ED. Care given at
the GPC is reasonably efficient and safe. Triage and treatment of self-referrals
by the GPC at ECAPs might offer opportunities for other countries facing problems
with inappropriate emergency department visits.
PMID- 28499356
TI - Erratum to: Out of hours care in Germany - High utilization by adult patients
with minor ailments?
PMID- 28499355
TI - Erratum to: Genome-wide association mapping and Identification of candidate genes
for fatty acid composition in Brassica napus L. using SNP markers.
PMID- 28499357
TI - Identification of a major Listeria monocytogenes outbreak clone linked to soft
cheese in Northern Italy - 2009-2011.
AB - BACKGROUND: Molecular subtyping and enhanced surveillance in Lombardy region
identified a cluster of possibly related listeriosis cases from 2006 to 2010.
This cluster grouped 31 isolates that belonged to serotype 1/2a and Sequence Type
38 (ST38) as defined by Multilocus Sequence Typing (MLST). METHODS: Our study
expanded the previous investigation to include cases from 2011 to 2014 and used
Multi-Virulence-Locus Sequence Typing (MVLST) on all ST38 isolates to better
understand their epidemiology and possibly identify a common source outbreak.
RESULTS: Out of 306 L. monocytogenes clinical isolates collected, 43 (14.1%)
belonged to ST38 with cases occurring in nine out of twelve Lombardy provinces.
The ST38 isolates were split by MVLST into two Virulence Types (VTs): VT80 (n =
12) and VT104 (n = 31). VT104 cases were concentrated between 2009 and 2011 in
two provinces, Bergamo and Milan. An epidemiologic investigation was performed
and in one case, a matching VT104 isolate was retrieved from a soft cheese sample
from a patient's refrigerator. CONCLUSIONS: Our findings revealed a major
listeriosis outbreak in Northern Italy linked to soft cheese in 2009-2011, which
went undetected by local health authorities. Our study shows that integrating
subtyping methods with conventional epidemiology can help identify the source of
L. monocytogenes outbreak clones.
PMID- 28499358
TI - Can we predict functional decline in hospitalized older people admitted through
the emergency department? Reanalysis of a predictive tool ten years after its
conception.
AB - BACKGROUND: In the Emergency Department (ED), early and rapid identification of
older people at risk of adverse outcomes, who could best benefit from complex
geriatric intervention, would avoid wasting time, especially in terms of
prevention of adverse outcomes, and ensure optimal orientation of vulnerable
patients. We wanted to test the predictive ability of a screening tool assessing
risk of functional decline (FD), named SHERPA, 10 years after its conception, and
to assess the added value of other clinical or biological factors associated with
FD. METHODS: A prospective cohort study of older patients (n = 305, >= 75 years)
admitted through the emergency department, for at least 48 h in non-geriatric
wards (mean age 82.5 +/- 4.9, 55% women). SHERPA variables (i.e. age, pre
admission instrumental Activity of Daily Living (ADL) status, falls within a
year, self-rated health and 21-point MMSE) were collected within 48 h of
admission, along with socio-demographic, medical and biological data. Functional
status was followed at 3 months by phone. FD was defined as a decrease at 3
months of at least one point in the pre-admission basic ADL score. Predictive
ability of SHERPA was assessed using c-statistic, predictive values and
likelihood ratios. Measures of discrimination improvement were Net
Reclassification Improvement and Integrated Discrimination Improvement. RESULTS:
One hundred and five patients (34%) developed 3-month FD. Predictive ability of
SHERPA decreased dramatically over 10 years (c = 0.73 vs. 0.64). Only two of its
constitutive variables, i.e. falls and instrumental ADL, were significant in
logistic regression analysis for functional decline, while 21-point MMSE was kept
in the model for clinical relevance. Demographic, comorbidity or laboratory data
available upon admission did not improve the SHERPA predictive yield.
CONCLUSIONS: Prediction of FD with SHERPA is difficult, but predictive factors,
i.e. falls, pre-existing functional limitation and cognitive impairment, stay
consistent across time and with literature. As accuracy of SHERPA and others
existing screening tools for FD is moderate, using these predictors as flags
instead of using composite scales can be a way to screen for high-risk patients.
PMID- 28499359
TI - Cystic fibrosis carriership and tuberculosis: hints toward an evolutionary
selective advantage based on data from the Brazilian territory.
AB - BACKGROUND: The reason why Cystic Fibrosis (CF) is the most common fatal genetic
disease among Caucasians has been incompletely studied. We aimed at deepening the
hypothesis that CF carriers have a relative protection against Mycobacterium
tuberculosis (Mtb) infection. METHODS: Applying spatial epidemiology, we studied
the link between CF carriership rate and tuberculosis (TB) incidence in Brazil.
We corrected for 5 potential environmental and 2 immunological confounders in
this relation: monthly income, sanitary provisions, literacy rates, racial
composition and population density along with AIDS incidence rates and diabetes
mellitus type 2. Smoking data were incomplete and not available for analysis.
RESULTS: A significant, negative correlation between CF carriership rate and TB
incidence, independent of any of the seven confounders was found. CONCLUSION: We
provide exploratory support for the hypothesis that carrying a single CFTR
mutation arms against Mtb infections.
PMID- 28499360
TI - Prevalence and correlates of cognitive impairment in kidney transplant
recipients.
AB - BACKGROUND: There is a high prevalence of cognitive impairment in dialysis
patients. The prevalence of cognitive impairment after kidney transplantation is
unknown. METHODS: Study Design: Cross-sectional study. SETTING AND PARTICIPANTS:
Single center study of prevalent kidney transplant recipients from a transplant
clinic in a large academic center. INTERVENTION: Assessment of cognition using
the Montreal Cognitive Assessment (MoCA). Demographic and clinical variables
associated with cognitive impairment were also examined. Outcomes and
Measurements: a) Prevalence of cognitive impairment defined by a MoCA score of
<26. b) Multivariable linear and logistic regression to examine the association
of demographic and clinical factors with cognitive impairment. RESULTS: Data from
226 patients were analyzed. Mean (SD) age was 54 (13.4) years, 73% were white,
60% were male, 37% had diabetes, 58% had an education level of college or above,
and the mean (SD) time since kidney transplant was 3.4 (4.1) years. The
prevalence of cognitive impairment was 58.0%. Multivariable linear regression
demonstrated that older age, male gender and absence of diabetes were associated
with lower MoCA scores (p < 0.01 for all). Estimated glomerular filtration rate
(eGFR) was not associated with level of cognition. The logistic regression
analysis confirmed the association of older age with cognitive impairment.
CONCLUSION: Cognitive impairment is common in prevalent kidney transplant
recipients, at a younger age compared to general population, and is associated
with certain demographic variables, but not level of eGFR.
PMID- 28499361
TI - Dietary diversity scores: an indicator of micronutrient inadequacy instead of
obesity for Chinese children.
AB - BACKGROUND: Micronutrient malnutrition affects the well-being of both adults and
children. Dietary diversity score (DDS) is a useful evaluation index with a
relatively well-developed guideline by FAO. It's meaningful to assess and predict
inadequate micronutrient intakes using DDS in Chinese children, after ruling out
the risk of obesity coming with more dietary diversity. METHODS: Data for
evaluation were extracted from the Nutrition Study of Preschool Children and
School Children, which is a cross-sectional study covering 8 cities of China,
including 1694 children in kindergartens and primary schools. This study applied
DDS to Chinese children to test the validity for micronutrient inadequacy, and
then explored the relationship between dietary diversity and obesity. RESULTS: It
reveals that dietary diversity varied with age and place of residence; the older
ones and the ones living in rural areas tend to have poorer dietary diversity.
Another discovery is that DDS is positively correlated with indicators of
micronutrient adequacy, with a score of 6-8 indicating the lowest risk of
micronutrient inadequacy in different groups of children. In our study
population, dietary diversity is not related with obesity. CONCLUSIONS: Dietary
diversity score is a valid indicator to evaluate micronutrient inadequacy in
Chinese children, though there is still room for improvement of the method.
Besides, the relationship between increase of dietary diversity and risk of
obesity should be treated circumspectly.
PMID- 28499362
TI - Active delivery of the anterior arm and incidence of second-degree perineal
tears: a clinical practice evaluation.
AB - BACKGROUND: Evaluate the feasibility of active delivery of the anterior arm
during spontaneous delivery. This maneuver could decrease incidence of second
degree perineal tears because it reduces fetal biacromial diameter. METHODS: An
observational comparative prospective study was conducted at our teaching
maternity from July 2012 to March 2013. The study included 199 nulliparous women
>=18 years, who met the following criteria: singleton pregnancy, vaginal delivery
with occiput anterior presentation, on epidural analgesia, from 37 weeks of
gestation onward. The distribution of rate and type of perineal tears were
compared between two groups: a non-exposed group and a group exposed to the
maneuver. RESULTS: A total of 101 patients were exposed to Couder's maneuver (CM)
and 98 patients were not exposed. In the intervention group, 3 failures of the
maneuver were reported. The maneuver was considered easy in 80% of cases,
moderately easy in 12% and difficult in 8% of cases. There was a significant
difference (p = 0.03) in the distribution of perineal tears between the two
groups. There was a significant reduction (p < 0.001) in the number of second
degree perineal tears in the patients exposed to CM. There was no significant
difference in the rate of anterior perineal trauma between the exposed and non
exposed arms. CONCLUSIONS: CM in primiparous women at term is feasible with a low
failure rate and influences the distribution of perineal tears by lowering second
degree perineal tears in a highly significant manner (p <0.01).
PMID- 28499363
TI - Predictors of response to prefabricated foot orthoses or rocker-sole footwear in
individuals with first metatarsophalangeal joint osteoarthritis.
AB - BACKGROUND: Osteoarthritis of the first metatarsophalangeal joint (1st MTPJ OA)
is a common and disabling condition commonly managed with footwear and orthotic
interventions. The objective of this study was to identify factors associated
with a successful treatment response in people with 1st MTPJ OA provided with
prefabricated orthoses or rocker-sole footwear as part of a randomised clinical
trial. METHODS: People with 1st MTPJ OA (n = 88) who participated in a randomised
trial were allocated to receive prefabricated foot orthoses (n = 47) or rocker
sole footwear (n = 41) and completed a baseline questionnaire including
information on demographics, anthropometrics, general health, pain
characteristics (including the Foot Health Status Questionnaire [FHSQ] and Foot
Function Index [FFI]) and perceptions of the interventions, and a clinical
assessment of foot posture, range of motion, radiographic severity and in-shoe
plantar pressures. Adherence was documented using diaries. At 12 weeks,
participants documented their perception of improvement on a 15-point scale.
Those reporting at least moderate improvement on this scale were classified as
'responders'. RESULTS: There were 29 responders (62%) in the orthoses group and
16 responders (39%) in the rocker-sole group. In the orthoses group, responders
had greater baseline pain severity while walking, a higher FFI difficulty score,
and wore their orthoses more frequently. In the rocker-sole group, responders had
a higher FFI stiffness score and greater radiographic severity. However, the
accuracy of these variables in identifying responders in each group was modest
(62 and 53%, respectively). CONCLUSION: The response to prefabricated orthoses or
rocker-sole footwear in people with 1st MTPJ OA is related to measures of
increased pain and disease severity. However, the overall classification accuracy
associated with these factors is not sufficient for identifying individuals who
are most likely to benefit from these interventions. TRIAL REGISTRATION:
Australian New Zealand Clinical Trials Registry: ACTRN12613001245785.
PMID- 28499364
TI - Clinical classification in low back pain: best-evidence diagnostic rules based on
systematic reviews.
AB - BACKGROUND: Clinical examination findings are used in primary care to give an
initial diagnosis to patients with low back pain and related leg symptoms. The
purpose of this study was to develop best evidence Clinical Diagnostic Rules
(CDR] for the identification of the most common patho-anatomical disorders in the
lumbar spine; i.e. intervertebral discs, sacroiliac joints, facet joints, bone,
muscles, nerve roots, muscles, peripheral nerve tissue, and central nervous
system sensitization. METHODS: A sensitive electronic search strategy using
MEDLINE, EMBASE and CINAHL databases was combined with hand searching and
citation tracking to identify eligible studies. Criteria for inclusion were:
persons with low back pain with or without related leg symptoms, history or
physical examination findings suitable for use in primary care, comparison with
acceptable reference standards, and statistical reporting permitting calculation
of diagnostic value. Quality assessments were made independently by two reviewers
using the Quality Assessment of Diagnostic Accuracy Studies tool. Clinical
examination findings that were investigated by at least two studies were included
and results that met our predefined threshold of positive likelihood ratio >= 2
or negative likelihood ratio <= 0.5 were considered for the CDR. RESULTS: Sixty
four studies satisfied our eligible criteria. We were able to construct promising
CDRs for symptomatic intervertebral disc, sacroiliac joint, spondylolisthesis,
disc herniation with nerve root involvement, and spinal stenosis. Single clinical
test appear not to be as useful as clusters of tests that are more closely in
line with clinical decision making. CONCLUSIONS: This is the first comprehensive
systematic review of diagnostic accuracy studies that evaluate clinical
examination findings for their ability to identify the most common patho
anatomical disorders in the lumbar spine. In some diagnostic categories we have
sufficient evidence to recommend a CDR. In others, we have only preliminary
evidence that needs testing in future studies. Most findings were tested in
secondary or tertiary care. Thus, the accuracy of the findings in a primary care
setting has yet to be confirmed.
PMID- 28499365
TI - Investigation of DNA repair-related SNPs underlying susceptibility to papillary
thyroid carcinoma reveals MGMT as a novel candidate gene in Belarusian children
exposed to radiation.
AB - BACKGROUND: Genetic factors may influence an individual's sensitivity to ionising
radiation and therefore modify his/her risk of developing papillary thyroid
carcinoma (PTC). Previously, we reported that common single nucleotide
polymorphisms (SNPs) within the DNA damage recognition gene ATM contribute to PTC
risk in Belarusian children exposed to fallout from the Chernobyl power plant
accident. Here we explored in the same population the contribution of a panel of
DNA repair-related SNPs in genes acting downstream of ATM. METHODS: The
association of 141 SNPs located in 43 DNA repair genes was examined in 75 PTC
cases and 254 controls from the Gomel region in Belarus. All subjects were
younger than 15 years at the time of the Chernobyl accident. Conditional logistic
regressions accounting for radiation dose were performed with PLINK using the
additive allelic inheritance model, and a linkage disequilibrium (LD)-based
Bonferroni correction was used for correction for multiple testing. RESULTS: The
intronic SNP rs2296675 in MGMT was associated with an increased PTC risk [per
minor allele odds ratio (OR) 2.54 95% CI 1.50, 4.30, P per allele = 0.0006, P
corr.= 0.05], and gene-wide association testing highlighted a possible role for
ERCC5 (P Gene = 0.01) and PCNA (P Gene = 0.05) in addition to MGMT (P Gene =
0.008). CONCLUSIONS: These findings indicate that several genes acting in
distinct DNA repair mechanisms contribute to PTC risk. Further investigation is
needed to decipher the functional properties of the methyltransferase encoded by
MGMT and to understand how alteration of such functions may lead to the
development of the most common type of thyroid cancer.
PMID- 28499366
TI - The role of BRCA1-IRIS in the development and progression of triple negative
breast cancers in Egypt: possible link to disease early lesion.
AB - BACKGROUND: Breast cancer is the most globally diagnosed female cancer, with the
triple negative breast cancer (TNBC) being the most aggressive subtype of the
disease. In this study we aimed at comparing the effect of BRCA1-IRIS
overexpression on the clinico-pathological characteristics in breast cancer
patients with TNBC or non-TNBC in the largest comprehensive cancer center in
Egypt. METHODS: To reach this goal, we conducted an observational study at the
National Cancer Institute (NCI), Cairo University (Cairo, Egypt). The data on all
diagnosed breast cancer patients, between 2009 and 2012, were reviewed. BRCA1
IRIS expression measured using real time RT/PCR in these patients' tumor samples
was correlated to tumor characteristics, such as to clinico-pathological
features, therapeutic responses, and survival outcomes. RESULTS: 96 patients were
enrolled and of these 45% were TNBC, and 55% were of other subtypes (hereafter,
non-TNBC). All patients presented with invasive ductal carcinomas. No significant
difference was observed for risk factors, such as age and menopausal status
between the TNBC and the non-TNBC groups except after BRCA1-IRIS expression was
factored in. The majority of the tumors in both groups were <=5 cm at surgery (p
= 0.013). However, in the TNBC group, <=5 cm tumors were BRCA1-IRIS
overexpressing, whereas in the non-TNBC group they were BRCA1-IRIS-negative (p =
0.00007). Most of the TNBC patients diagnosed with grade 1 or 2 were BRCA1-IRIS
overexpressing, whereas non-TNBCs were IRIS-negative (p = 0.00035). No
statistical significance was measured in patients diagnosed with grade 3 tumors.
Statistically significant difference between TNBCs and non-TNBCs and tumor stage
with regard to BRCA1-IRIS-overexpression was observed. Presence of axillary lymph
node metastases was positively associated with BRCA1-IRIS overexpression in TNBC
group, and with BRCA1-IRIS-negative status in the non-TNBC group (p = 0.00009).
Relapse after chemotherapy (p < 0.00001), and local recurrence/distant metastasis
after surgery (p = 0.0028) were more pronounced in TNBC patients with BRCA1-IRIS
overexpressing tumors compared to non-TNBC patients. Finally, decreased disease
free survival in TNBC/BRCA1-IRIS-overexpressing patients compared to TNBC/BRCA1
IRIS-negative patients, and decreased overall survival in TNBC as well as non
TNBC patients was driven by BRCA1-IRIS overexpression. CONCLUSIONS: TNBC/BRCA1
IRIS-overexpressing tumors are more aggressive than TNBC/BRCA1-IRIS-negative or
non-TNBC/BRCA1-IRIS-overexpressing or both negative tumors. Further studies are
warranted to define whether BRCA1-IRIS drives the early TNBC lesions growth and
dissemination and whether it could be used as a diagnostic biomarker and/or
therapeutic target for these lesions at an early stage setting.
PMID- 28499367
TI - The effectiveness of long-needle acupuncture at acupoints BL30 and BL35 for
CP/CPPS: a randomized controlled pilot study.
AB - BACKGROUND: The chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is one
of the commonest chronic inflammatory diseases in adult men, for which
acupuncture has been used to relieve related symptoms. The present study aimed to
evaluate the therapeutic effect of the long-needle acupuncture on CP/CPPS.
METHODS: A randomized traditional acupuncture-controlled single blind study was
conducted on 77 patients who were randomized into long-needle acupuncture (LA)
and traditional acupuncture (TA) groups. The patients received six sessions of
acupuncture for 2 weeks and a follow-up was scheduled at week 24. The primary
outcome was measured by the total National Institutes of Health-Chronic
Prostatitis Symptom Index (NIH-CPSI) score at week 2. Four domains of the NIH
CPSI (urination, pain or discomfort, effects of symptoms, and quality of life)
and the clinical efficacy score served as the secondary outcome. RESULTS: The
total NIH-CPSI score at week 2 and week 24 was significantly improved in the LA
group compared with the TA group. LA significantly improved urination, pain or
discomfort, the effects of symptoms, and the quality of life at week 2 and week
24 and patients undergoing LA treatment had a higher clinical efficacy score.
CONCLUSION: Needling at the BL30 and BL35 using LA benefits patients with
CP/CPPS. TRIAL REGISTRATION: The study was registered at the Chinese Clinical
Trial Register ( ChiCTR-ICR-15006138 ).
PMID- 28499368
TI - Measuring mental well-being in Norway: validation of the Warwick-Edinburgh Mental
Well-being Scale (WEMWBS).
AB - BACKGROUND: Mental well-being is an important, yet understudied, area of
research, partly due to lack of appropriate population-based measures. The
Warwick-Edinburgh Mental Well-being Scale (WEMWBS) was developed to meet the
needs for such a measure. This article assesses the psychometric properties of
the Norwegian version of the WEMWBS, and its short-version (SWEMWBS) among a
sample of primary health care patients who participated in the evaluation of
Prompt Mental Health Care (PMHC), a novel Norwegian mental health care program
aimed to increase access to treatment for anxiety and depression. METHODS:
Forward and back-translations were conducted, and 1168 patients filled out an
electronic survey including the WEMWBS, and other mental health scales. The
original dataset was randomly divided into a training sample (~70%) and a
validation sample (~30%). Parallel analysis and confirmatory factor analysis were
carried out to assess construct validity and precision. The final models were
cross-validated in the validation sample by specifying a model with fixed
parameters based on the estimates from the trainings set. Criterion validity and
measurement invariance of the (S)WEMWBS were examined as well. RESULTS: Support
was found for the single factor hypothesis in both scales, but similar to
previous studies, only after a number of residuals were allowed to correlate
(WEMWBS: CFI = 0.99; RMSEA = 0.06, SWEMWBS: CFI = .99; RMSEA = 0.06). Further
analyses showed that the correlated residuals did not alter the meaning of the
underlying construct and did not substantially affect the associations with other
variables. Precision was high for both versions of the WEMWBS (>.80), and scalar
measurement invariance was obtained for gender and age group. The final
measurement models displayed adequate fit statistics in the validation sample as
well. Correlations with other mental health scales were largely in line with
expectations. No statistically significant differences were found in mean latent
(S)WEMWBS scores for age and gender. CONCLUSION: Both WEMWBS scales appear to be
valid and precise instruments to measure mental well-being in primary health care
patients. The results encourage the use of mental well-being as an outcome in
future epidemiological, clinical, and evaluation studies, and may as such be
valuable for both research and public health practice.
PMID- 28499369
TI - Characterization of a splice-site mutation in the tumor suppressor gene FLCN
associated with renal cancer.
AB - BACKGROUND: Renal cell carcinoma is among the most prevalent malignancies. It is
generally sporadic. However, genetic studies of rare familial forms have led to
the identification of mutations in causative genes such as VHL and FLCN.
Mutations in the FLCN gene are the cause of Birt-Hogg-Dube syndrome, a rare tumor
syndrome which is characterized by the combination of renal cell carcinoma,
pneumothorax and skin tumors. METHODS: Using Sanger sequencing we identify a
heterozygous splice-site mutation in FLCN in lymphocyte DNA of a patient
suffering from renal cell carcinoma. Furthermore, both tumor DNA and DNA from a
metastasis are analyzed regarding this mutation. The pathogenic effect of the
sequence alteration is confirmed by minigene assays and the biochemical
consequences on the protein are examined using TALEN-mediated transgenesis in
cultured cells. RESULTS: Here we describe an FLCN mutation in a 55-year-old
patient who presented himself with progressive weight loss, bilateral kidney
cysts and renal tumors. He and members of his family had a history of recurrent
pneumothorax during the last few decades. Histology after tumor nephrectomy
showed a mixed kidney cancer consisting of elements of a chromophobe renal cell
carcinoma and dedifferentiated small cell carcinoma component. Subsequent FLCN
sequencing identified an intronic c.1177-5_-3delCTC alteration that most likely
affected the correct splicing of exon 11 of the FLCN gene. We demonstrate
skipping of exon 11 to be the consequence of this mutation leading to a shift in
the reading frame and the insertion of a premature stop codon. Interestingly, the
truncated protein was still expressed both in cell culture and in tumor tissue,
though it was strongly destabilized and its subcellular localization differed
from wild-type FLCN. Both, altered protein stability and subcellular localization
could be partly reversed by blocking proteasomal and lysosomal degradation.
CONCLUSIONS: Identification of disease-causing mutations in BHD syndrome requires
the analysis of intronic sequences. However, biochemical validation of the
consecutive alterations of the resulting protein is especially important in these
cases. Functional characterization of the disease-causing mutations in BHD
syndrome may guide further research for the development of novel diagnostic and
therapeutic strategies.
PMID- 28499371
TI - "Placebo effect is probably what we refer to as patient healing power": A
qualitative pilot study examining how Norwegian complementary therapists reflect
on their practice.
AB - BACKGROUND: Complementary therapists spend considerable time with their patients,
especially in the first consultation. The communication between patients and
their therapists is important for raising consciousness and activation of the
patient's self-healing power. Thus, the aims in this study were to delineate what
complementary therapists regard as essential in patient consultations, their view
of the healing process, and how the therapists understand the placebo effect and
its position in the healing process. METHODS: Semi-structured individual
interviews (n = 4), focus group interview (n = 1) and participant observation
were conducted among four different complementary therapists in a Norwegian
community. The text data was transcribed verbatim and the analysis of the
material was conducted according to conventional and direct content analysis.
Some codes were predefined and others were defined during the analysis. RESULTS:
The pilot study showed that the implemented methods seems feasible and fit well
with the aims of this study. Complementary therapists (chiropractor, naprapath
(musculoskeletal therapist), acupuncturist and acupuncturist/homeopath)
representing four different complementary modalities participated. A combination
of the conversation and examination during the first consultation formed the
basis for the therapist's choice of treatment. A successful consultation was
characterized by a fruitful relationship between the therapist and the patient.
Moreover, the therapist needs to be humble and show the patient respect.
Patients' positive beliefs and expectations about the treatment play a
significant role in the healing process. The more hope the therapist can bring
about, the more easily the patient can start believing that it is possible to get
well. CONCLUSION: This was a pilot study. Therefore the findings should be
appreciated as limited and preliminary. Therapists' and patients' mutual
understanding and treatment goals were essential for a successful consultation.
The therapists emphasized their professional skills and therapeutic competence as
important when building fruitful relationships with their patients. Exerting
authority and making the patient feel confident were essential factors for a
successful healing process. The complementary therapists understood the placebo
effect as the patient's self-healing power, resulting from establishing trust and
belief in the treatment process.
PMID- 28499370
TI - Is hydroxychloroquine effective in treating primary Sjogren's syndrome: a
systematic review and meta-analysis.
AB - BACKGROUND: To systematically review and assess the efficacy and safety of
hydroxychloroquine (HCQ) for treating primary Sjogren's syndrome (pSS). METHODS:
Five electronic databases (Pubmed, EMBASE, Web of science, Ovid, Cochrane
Library) were searched for randomized controlled trials and retrospective or
prospective studies published in English that reported the effect of HCQ on pSS.
The subjective symptoms ( sicca symptoms, fatigue and pain) and the objective
indexes (erythrocyte sedimentation rate and Schirmer test) were assessed as main
outcome measures. A meta-analysis and descriptive study on the efficacy and
safety of HCQ were conducted. The estimate of the effect of HCQ treatment was
expressed as a proportion together with 95% confidence interval, and plotted on a
forest plot. RESULTS: Four trials with totals of 215 SS patients, including two
randomized controlled trials, one double blind crossover trial and one
retrospective open-label study, were analyzed in this review. For dry mouth and
dry eyes, the effectiveness of HCQ treatment was essentially the same as placebo
treatment. For fatigue, the effectiveness of HCQ was lower than placebo. The
efficacy of HCQ in treating pain associated with pSS was superior to that of the
placebo. There was no significant difference between HCQ-treated groups and
controls in terms of Schirmer test results, but HCQ could reduce the erythrocyte
sedimentation rate compare with placebo. A descriptive safety assessment showed
that gastrointestinal adverse effects were the most common adverse effects
associated with HCQ. CONCLUSIONS: This systematic review showed that there is no
significant difference between HCQ and placebo in the treatment of dry mouth and
dry eye in pSS. Well-designed, randomized, controlled trials are needed to
provide higher-quality evidence to confirm our findings, and future studies
should focus on some other i n dex or extraglandular measures, such as
cutaneous manifestations, to further explore the therapeutic effect of HCQ in
pSS.
PMID- 28499372
TI - Persons with rheumatoid arthritis challenge the relevance of the health
assessment questionnaire: a qualitative study of patient perception.
AB - BACKGROUND: The Stanford Health Assessment Questionnaire-Disability Index (HAQ)
is widely used to measure functional ability in persons with Rheumatoid Arthritis
(RA). The instrument was developed with limited involvement from persons with RA,
and their perception of the instrument has not been studied in depth. The aim of
this study was to explore how persons with RA experience the use of the HAQ in
care. METHODS: The study used secondary data analysis. Persons with RA
participated in semi-structured interviews in previous research projects. Thirty
nine interviews were included based on data fit, and thematic analysis applied.
RESULTS: The participants questioned the relevance of the HAQ but nevertheless
experienced that the instrument had a profound effect on their understanding of
health and how care is delivered. The analysis resulted in three themes: Problems
with individual items, meaning of the summative score, and effects on care and
health perceptions. CONCLUSIONS: To make the HAQ relevant to persons with RA, it
needs to be revised or to include an option to select items most meaningful to
the respondent. To ensure relevance, the HAQ update should preferably be co
created by researchers, clinicians and persons with RA.
PMID- 28499373
TI - A case-control study of selenoprotein genes polymorphisms and autoimmune thyroid
diseases in a Chinese population.
AB - BACKGROUND: Selenium is an essential trace and there is a high selenium
concentration in the thyroid gland. Selenium deficiency may impair the thyroid
function. The aim of this study was to investigate the association between three
selenoprotein genes polymorphisms and autoimmune thyroid diseases. METHODS: We
genotyped six single-nucleotide polymorphisms (SNPs), rs6865453 in selenoprotein
P gene (SELENOP), rs713041 rs2074451 rs3746165 in glutathione peroxidase 4 gene
(GPX4) and rs28665122 and rs7178239 in selenoprotein S gene (SELENOS) by
MassARRAY system using the chip-based matrix-assisted laser desorption ionization
time-of-flight mass spectrometry technology in 1060 patients with autoimmune
thyroid diseases and 938 healthy controls. RESULTS: Major alleles in rs6865453 of
SELENOP, rs713041, rs2074451, rs3746165 of GPX4 decreased while the major allele
C in rs28665122 of SELENOS increased in AITD patients than in the control. The
allele C and genotype CC in rs7178239 of SELENOS showed different trend in GD and
HT patients when compared with the control. All the distribution difference
showed nonsignificant. Analysis according to clinical features including
ophthalmopathy, hypothyroidism and family history came out to be negative either.
CONCLUSIONS: Our findings suggest non-association between three selenoprotein
genes and AITD, conflicting to the positive result in another population.
Different selenium nutrition status in different populations may contribute to
conflicting results, the contribution of genetic variants in AITD mechanism may
be another reason.
PMID- 28499374
TI - Clinical improvement of renal amyloidosis in a patient with systemic-onset
juvenile idiopathic arthritis who received tocilizumab treatment: a case report
and literature review.
AB - BACKGROUND: Juvenile idiopathic arthritis (JIA) is a common rheumatic disease in
children and adolescents. Although JIA may cause secondary amyloidosis, this is a
rare complication in patients with JIA and other rheumatic diseases. Many
previous studies have revealed that common heterozygous or homozygous mutations
in the MEFV gene are associated with systemic-onset JIA (SJIA). CASE
PRESENTATION: We herein report a case involving a 19-year-old female patient with
difficult-to-control SJIA. She developed progressive proteinuria without clinical
signs or symptoms of edema. Renal amyloidosis was diagnosed by renal pathologic
examination, which demonstrated deposition of eosinophilic amorphous material in
the interlobular arteries, arterioles, and interstitium. Electron microscopy
showed fibrillary material deposits with a diameter of 8 to 10 nm. A heterozygous
E148Q mutation in the MEFV gene was identified. Conventional disease-modifying
anti-rheumatic drugs and etanercept had been used to treat the SJIA, but the
disease could not be controlled. Therefore, we decided to start tocilizumab to
control the disease activity. However, the patient was unable to receive a
standard dose of tocilizumab in the early period of treatment because of
socioeconomic limitations. Her disease course was still active, and proteinuria
was found. Therefore, tocilizumab was increased to a dose of 8 mg/kg every 2
weeks (standard dose of SJIA), and the patient exhibited a clinical response
within 3 months. CONCLUSION: Refractory SJIA associated with renal amyloidosis is
an uncommon cause of proteinuria in adolescents. Tocilizumab may be a beneficial
treatment for renal amyloidosis in patients with SJIA.
PMID- 28499375
TI - Cardiovascular risk status of Afro-origin populations across the spectrum of
economic development: findings from the Modeling the Epidemiologic Transition
Study.
AB - BACKGROUND: Cardiovascular risk factors are increasing in most developing
countries. To date, however, very little standardized data has been collected on
the primary risk factors across the spectrum of economic development. Data are
particularly sparse from Africa. METHODS: In the Modeling the Epidemiologic
Transition Study (METS) we examined population-based samples of men and women,
ages 25-45 of African ancestry in metropolitan Chicago, Kingston, Jamaica, rural
Ghana, Cape Town, South Africa, and the Seychelles. Key measures of
cardiovascular disease risk are described. RESULTS: The risk factor profile
varied widely in both total summary estimates of cardiovascular risk and in the
magnitude of component factors. Hypertension ranged from 7% in women from Ghana
to 35% in US men. Total cholesterol was well under 200 mg/dl for all groups, with
a mean of 155 mg/dl among men in Ghana, South Africa and Jamaica. Among women
total cholesterol values varied relatively little by country, following between
160 and 178 mg/dl for all 5 groups. Levels of HDL-C were virtually identical in
men and women from all study sites. Obesity ranged from 64% among women in the US
to 2% among Ghanaian men, with a roughly corresponding trend in diabetes. Based
on the Framingham risk score a clear trend toward higher total risk in
association with socioeconomic development was observed among men, while among
women there was considerable overlap, with the US participants having only a
modestly higher risk score. CONCLUSIONS: These data provide a comprehensive
estimate of cardiovascular risk across a range of countries at differing stages
of social and economic development and demonstrate the heterogeneity in the
character and degree of emerging cardiovascular risk. Severe
hypercholesterolemia, as characteristic in the US and much of Western Europe at
the onset of the coronary epidemic, is unlikely to be a feature of the
cardiovascular risk profile in these countries in the foreseeable future,
suggesting that stroke may remain the dominant cardiovascular event.
PMID- 28499376
TI - Benefits of preparing for childbirth with mindfulness training: a randomized
controlled trial with active comparison.
AB - BACKGROUND: Childbirth fear is linked with lower labor pain tolerance and worse
postpartum adjustment. Empirically validated childbirth preparation options are
lacking for pregnant women facing this problem. Mindfulness approaches, now
widely disseminated, can alleviate symptoms of both chronic and acute pain and
improve psychological adjustment, suggesting potential benefit when applied to
childbirth education. METHODS: This study , the Prenatal Education About Reducing
Labor Stress (PEARLS) study, is a randomized controlled trial (RCT; n = 30) of a
short, time-intensive, 2.5-day mindfulness-based childbirth preparation course
offered as a weekend workshop , the Mind in Labor (MIL): Working with Pain in
Childbirth, based on Mindfulness-Based Childbirth and Parenting (MBCP) education.
First-time mothers in the late 3rd trimester of pregnancy were randomized to
attend either the MIL course or a standard childbirth preparation course with no
mind-body focus. Participants completed self-report assessments pre-intervention,
post-intervention, and post-birth, and medical record data were collected.
RESULTS: In a demographically diverse sample, this small RCT demonstrated
mindfulness-based childbirth education improved women's childbirth-related
appraisals and psychological functioning in comparison to standard childbirth
education. MIL program participants showed greater childbirth self-efficacy and
mindful body awareness (but no changes in dispositional mindfulness), lower post
course depression symptoms that were maintained through postpartum follow-up, and
a trend toward a lower rate of opioid analgesia use in labor. They did not,
however, retrospectively report lower perceived labor pain or use epidural less
frequently than controls. CONCLUSIONS: This study suggests mindfulness training
carefully tailored to address fear and pain of childbirth may lead to important
maternal mental health benefits, including improvements in childbirth-related
appraisals and the prevention of postpartum depression symptoms. There is also
some indication that MIL participants may use mindfulness coping in lieu of
systemic opioid pain medication. A large-scale RCT that captures real-time pain
perceptions during labor and length of labor is warranted to provide a more
definitive test of these effects. TRIAL REGISTRATION: The ClinicalTrials.gov
identifier for the PEARLS study is: NCT02327559 . The study was retrospectively
registered on June 23, 2014.
PMID- 28499377
TI - Calculating hospital length of stay using the Hospital Episode Statistics; a
comparison of methodologies.
AB - BACKGROUND: Accurate calculation of hospital length of stay (LOS) from the
English Hospital Episode Statistics (HES) is important for a wide range of audit
and research purposes. The two methodologies which are commonly used to achieve
this differ in their accuracy and complexity. We compare these methods and make
recommendations on when each is most appropriate. METHODS: We calculated LOS
using continuous inpatient spells (CIPS), which link care spanning across
multiple hospitals, and spells, which do not, for six conditions with short
(dyspepsia or other stomach function, ENT infection), medium (dehydration and
gastroenteritis, perforated or bleeding ulcer), and long (stroke, fractured
proximal femur) average LOS. We examined how inter-area comparisons (i.e.
benchmarking) and temporal trends differed. We defined a classification system
for spells and explored the causes of differences. RESULTS: Stroke LOS was 16.5
days using CIPS but 24% (95% CI: 23, 24) lower, at 12.6 days, using spells.
Smaller differences existed for shorter-LOS conditions including dehydration and
gastroenteritis (4.5 vs. 4.2 days) and ENT infection (0.9 vs. 0.8 days). Typical
patient pathways differed markedly between areas and have evolved over time. One
area had the third shortest stroke LOS (out of 151) using spells but the fourth
longest using CIPS. These issues were most profound for stroke and fractured
proximal femur, as patients were frequently transferred to a separate hospital
for rehabilitation, however important disparities also existed for conditions
with simpler secondary care pathways (e.g. ENT infections, dehydration and
gastroenteritis). CONCLUSIONS: Spell-based LOS is widely used by researchers and
national reporting organisations, including the Health and Social Care
Information Centre, however it can substantially underestimate the time patients
spend in hospital. A widespread shift to a CIPS methodology is required to
improve the quality of LOS estimates and the robustness of research and
benchmarking findings. This is vital when investigating clinical areas with
typically long, complex patient pathways. Researchers should ensure that their
LOS calculation methodology is fully described and explicitly acknowledge
weaknesses when appropriate.
PMID- 28499378
TI - Organisational systems' approaches to improving cultural competence in
healthcare: a systematic scoping review of the literature.
AB - INTRODUCTION: Healthcare organisations serve clients from diverse Indigenous and
other ethnic and racial groups on a daily basis, and require appropriate client
centred systems and services for provision of optimal healthcare. Despite
advocacy for systems-level approaches to cultural competence, the primary focus
in the literature remains on competency strategies aimed at health promotion
initiatives, workforce development and student education. This paper aims to
bridge the gap in available evidence about systems approaches to cultural
competence by systematically mapping key concepts, types of evidence, and gaps in
research. METHODS: A literature search was completed as part of a larger
systematic search of evaluations and measures of cultural competence
interventions in health care in Canada, the United States, Australia and New
Zealand. Seventeen peer-reviewed databases, 13 websites and clearinghouses, and
11 literature reviews were searched from 2002 to 2015. Overall, 109 studies were
found, with 15 evaluating systems-level interventions or describing measurements.
Thematic analysis was used to identify key implementation principles,
intervention strategies and outcomes reported. RESULTS: Twelve intervention and
three measurement studies met our inclusion criteria. Key principles for
implementing systems approaches were: user engagement, organisational readiness,
and delivery across multiple sites. Two key types of intervention strategies to
embed cultural competence within health systems were: audit and quality
improvement approaches and service-level policies or strategies. Outcomes were
found for organisational systems, the client/practitioner encounter, health, and
at national policy level. DISCUSSION AND IMPLICATIONS: We could not determine the
overall effectiveness of systems-level interventions to reform health systems
because interventions were context-specific, there were too few comparative
studies and studies did not use the same outcome measures. However, examined
together, the intervention and measurement principles, strategies and outcomes
provide a preliminary framework for implementation and evaluation of systems
level interventions to improve cultural competence. Identified gaps in the
literature included a need for cost and effectiveness studies of systems
approaches and explication of the effects of cultural competence on client
experience. Further research is needed to explore the extent to which cultural
competence improves health outcomes and reduces ethnic and racially-based
healthcare disparities.
PMID- 28499379
TI - Diet with a combination of high protein and high total antioxidant capacity is
strongly associated with low prevalence of frailty among old Japanese women: a
multicenter cross-sectional study.
AB - BACKGROUND: The intake of protein and antioxidants has been inversely associated
with frailty, individually. However, to our knowledge, no study has evaluated
these associations in considering antioxidants or protein intakes as respective
confounders. Further, the cooperative effect of dietary protein and antioxidants
on frailty has not been investigated. Therefore, we examined the association of
high protein and high dietary total antioxidant capacity (TAC) with frailty under
the adjustment for dietary TAC or protein intake, respectively. The association
between the combination of high dietary protein and high dietary TAC and frailty
was also investigated. METHODS: A total of 2108 grandmothers or acquaintances of
dietetic students aged 65 years and older participated in this cross-sectional
multicenter study conducted in 85 dietetic schools in Japan. Dietary variables,
including protein intake, and dietary TAC were estimated from a validated brief
type self-administered diet history questionnaire. Frailty was defined as a score
of three or more points obtained from the following four components: slowness and
weakness (two points), exhaustion, low physical activity, and unintentional
weight loss. RESULTS: Median (interquartile range) age of the present subjects
was 74 (71-78) years. Multivariate adjusted ORs (95% CIs) for frailty in the
highest compared to the lowest tertile were 0.66 (0.49, 0.87) for total protein
intake (P for trend = 0.003) and 0.51 (0.37, 0.69) for dietary TAC (P for trend
<0.0001) after adjustment for dietary TAC or total protein intake, respectively.
The OR of frailty for the group with both the highest tertiles of total protein
intake and dietary TAC was markedly lower (multivariate adjusted OR [95% CIs]:
0.27 [0.16, 0.44]; P <0.0001) compared to the group with the lowest tertile of
protein intake and the lowest tertile of dietary TAC. CONCLUSIONS: Both protein
intake and dietary TAC were independently inversely associated with frailty among
old Japanese women. Further, a diet with the combination of high dietary protein
and high dietary TAC was strongly inversely associated with the prevalence of
frailty in this population. To select food combinations that allow for an
increase of both protein and antioxidants in diet according to the local food
culture and dietary habits may be an effective strategy for frailty prevention.
PMID- 28499380
TI - Erratum to: Implementing 360 degrees Quantified Self for childhood obesity:
feasibility study and experiences from a weight loss camp in Qatar.
PMID- 28499381
TI - Experience in the use of non-pneumatic anti-shock garment (NASG) in the
management of postpartum haemorrhage with hypovolemic shock in the Fundacion
Valle Del Lili, Cali, Colombia.
AB - BACKGROUND: The aim of this case series is to describe the experience of using
the non-pneumatic anti-shock garment (NASG) in the management of severe
Postpartum hemorrhage (PPH) and shock, and the value of implementing this concept
in high-complexity obstetric hospitals. METHODS: Descriptive case series of 77
women that received NASG in the management of PPH with severe hypovolemic shock
from June 2014 to December 2015. Vital signs, shock index (SI), the lactic acid
value and the base deficit were compared before and after NASG application.
RESULTS: Fifty-six (77%) women had an SI > 1.1 at the time shock management was
initiated; 96% had uterine atony. All women received standard does of
uterotonics. The average time between the birth and NASG applications was 20 min.
Forty-eight percent of women recovered haemodynamic variables in the first hour
and 100% within the first 6 h; 100% had a SI < 1.0 in the first hour. The NASG
was not removed until definitive control of bleeding was achieved, with an
average time of use of 24 h. There were no mortalities. CONCLUSIONS: In this case
series of women in severe shock, the NASG was an effective management device for
the control of severe hypovolemic shock. It should be considered a first-line
option for shock management.
PMID- 28499382
TI - The association between residential eviction and syringe sharing among a
prospective cohort of street-involved youth.
AB - BACKGROUND: Syringe sharing is a high-risk practice associated with the
transmission of infectious diseases, such as HIV and HCV. While youth who contend
with housing instability are known to be more likely to engage in high-risk
substance use, the potential relationship between being evicted from housing and
syringe sharing has not been examined. This study assessed whether residential
eviction was associated with syringe sharing among street-involved youth in
Vancouver, Canada. METHODS: Data were derived from the At-Risk Youth Study
(ARYS), a prospective cohort of street-involved youth who use drugs age 14-26 in
Vancouver, Canada. The study period was June 2007 to May 2014, and the potential
relationship between residential eviction and syringe sharing was analyzed using
multivariable generalized estimating equations (GEE) logistic regression.
RESULTS: Among 405 street-involved youth who injected drugs, 149 (36.8%) reported
syringe sharing, defined as borrowing or lending a syringe, at some point during
the study period. In a multivariable GEE analysis, recent residential eviction
remained independently associated with syringe sharing (adjusted odds ratio (AOR)
= 1.72, 95% confidence interval (CI): 1.16-2.57), after adjusting for potential
confounders. CONCLUSIONS: Syringe sharing was significantly elevated among youth
who had recently been evicted from housing. These findings indicate that policy
and programmatic interventions that increase housing stability may help mitigate
high-risk substance use practices among vulnerable youth.
PMID- 28499383
TI - Nintedanib antiangiogenic inhibitor effectiveness in delaying adenocarcinoma
progression in Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP).
AB - BACKGROUND: In recent times, anti-cancer treatments have focused on Fibroblast
Growth Factor (FGF) and Vascular-Endothelial Growth Factor (VEGF) pathway
inhibitors so as to target tumor angiogenesis and cellular proliferation. One
such drug is Nintedanib; the present study evaluated the effectiveness of
Nintedanib treatment against in vitro proliferation of human prostate cancer
(PCa) cell lines, and growth and progression of different grades of PCa lesions
in pre-clinical PCa transgenic adenocarcinoma for the mouse prostate (TRAMP)
model. METHODS: Both androgen-independent (LNCaP) and androgen-dependent (PC3)
PCa cell lines were treated with a range of Nintedanib doses for 72 h, and effect
on cell growth and expression of angiogenesis associated VEGF receptors was
analyzed. In pre-clinical efficacy evaluation, male TRAMP mice starting at 8 and
12 weeks of age were orally-fed with vehicle control (10% Tween 20) or Nintedanib
(10 mg/Kg/day in vehicle control) for 4 weeks, and sacrificed immediately after 4
weeks of drug treatment or sacrificed 6-10 weeks after stopping drug treatments.
At the end of treatment schedule, mice were sacrificed and ventral lobe of
prostate was excised along with essential metabolic organ liver, and subjected to
histopathological and extensive molecular evaluations. RESULTS: The total cell
number decreased by 56-80% in LNCaP and 45-93% in PC3 cells after 72 h of
Nintedanib treatment at 2.5-25 MUM concentrations. In pre-clinical TRAMP studies,
Nintedanib led to a delay in tumor progression in all treatment groups; the
effect was more pronounced when treatment was given at the beginning of the
glandular lesion development and continued till study end. A decreased
microvessel density and VEGF immunolocalization was observed, besides decreased
expression of Androgen Receptor (AR), VEGFR-1 and FGFR-3 in some of the treated
groups. No changes were observed in the histological liver analysis. CONCLUSIONS:
Nintedanib treatment was able to significantly decrease the growth of PCa cell
lines and also delay growth and progression of PCa lesions to higher grades of
malignancy (without inducing any hepatotoxic effects) in TRAMP mice. Furthermore,
it was observed that Nintedanib intervention is more effective when administered
during the early stages of neoplastic development, although the drug is capable
of reducing cell proliferation even after treatment interruption.
PMID- 28499384
TI - Quality of care in family planning services in Senegal and their outcomes.
AB - BACKGROUND: High quality of care in family planning (FP) services has been found
to be associated with increased and continued use of contraceptive methods. The
interpersonal skills and technical competence of the provider is one of the main
components of quality of care. To study the process component of quality of care,
the distribution of the FP counseling topics was examined by client, provider and
facility characteristics. To assess the outcomes of quality of care, client
satisfaction and their knowledge of their method's protection from STIs were
used. This study examined the factors associated with these outcomes with a focus
on provider counseling and training. METHODS: Data from the 2012-2013 Senegal
Service Provision Assessment survey was used for the analysis. The survey
included a representative sample of the health facilities in Senegal and collects
data by observing the clients' FP visits and conducting exit interviews. The main
outcomes of interest were provider's counseling in FP, client's satisfaction with
FP services and client's knowledge of their method's protection from STIs.
Several covariates were used in the analysis which represent client, provider and
facility characteristics. RESULTS: The level of counseling was inadequate-- very
low proportions of providers that performed different types of counseling.
Counseling was more likely to be provided to new than returning clients.
Approximately 84% of the clients were very satisfied with services but only 58%
had correct knowledge of their method's protection from STIs. Clients were
significantly less likely to be very satisfied when their providers counseled on
side effects and when to return, and counseling provided on method's protection
from STIs did not significantly improve knowledge in this area. Clients seen by a
provider with FP training had almost twice the odds of having correct knowledge
about their method's protection from STIs compared with clients seen by a
provider with no recent training. CONCLUSIONS: The percentage of providers
offering FP counseling to their clients was relatively low and was ineffective on
the client-focused outcomes. Interventions may be required for more effective
counseling methods that are client-centered as well as providing more FP training
to providers.
PMID- 28499385
TI - Target organ damage and incident type 2 diabetes mellitus: the Strong Heart
Study.
AB - BACKGROUND: Recent analyses in a registry of hypertensive patients suggested that
preceding left ventricular (LV) hypertrophy (LVH) and/or carotid atherosclerosis
are associated with incident type 2 diabetes, independent of confounders. We
assess the relation between prevalent cardio-renal target organ damage (TOD) and
subsequent incident type 2 diabetes in a population-based study with high
prevalence of obesity. METHODS: We selected 2887 non-diabetic participants from
two cohorts of the Strong Heart Study (SHS). Clinical exam, laboratory tests and
echocardiograms were performed. Adjudicated TODs were LVH, left atrium (LA)
dilatation, and high urine albumin/creatinine ratio (UACR). Multivariable
logistic regression models were used to identify variables responsible for the
association between initial TODs and incident diabetes at 4-year follow-up (FU).
RESULTS: After 4 years, 297 new cases of diabetes (10%) were identified, 216 of
whom exhibited baseline impaired fasting glucose (IFG, 73%, p < 0.0001).
Participants developing type 2 diabetes exhibited higher inflammatory markers,
fat-free mass and adipose mass and higher prevalence of initial LVH and LA
dilatation than those without (both p < 0.04). In multivariable logistic
regression, controlling for age, sex, family relatedness, presence of arterial
hypertension and IFG, all three indicators of TOD predicted incident diabetes
(all p < 0.01). However, the effects of TOD was offset when body fat and
inflammatory markers were introduced into the model. CONCLUSIONS: In this
population-based study with high prevalence of obesity, TOD precedes clinical
appearance of type 2 diabetes and is related to the preceding metabolic status,
body composition and inflammatory status. Trial registration Trial registration
number: NCT00005134, Name of registry: Strong Heart Study, URL of registry:
https://clinicaltrials.gov/ct2/show/NCT00005134, Date of registration: May 25,
2000, Date of enrolment of the first participant to the trial: September 1988.
PMID- 28499386
TI - Gender equality and human rights approaches to female genital mutilation: a
review of international human rights norms and standards.
AB - Two hundred million girls and women in the world are estimated to have undergone
female genital mutilation (FGM), and another 15 million girls are at risk of
experiencing it by 2020 in high prevalence countries (UNICEF, 2016. Female
genital mutilation/cutting: a global concern. 2016). Despite decades of concerted
efforts to eradicate or abandon the practice, and the increased need for clear
guidance on the treatment and care of women who have undergone FGM, present
efforts have not yet been able to effectively curb the number of women and girls
subjected to this practice (UNICEF. Female genital mutilation/cutting: a
statistical overview and exploration of the dynamics of change. 2013), nor are
they sufficient to respond to health needs of millions of women and girls living
with FGM. International efforts to address FGM have thus far focused primarily on
preventing the practice, with less attention to treating associated health
complications, caring for survivors, and engaging health care providers as key
stakeholders. Recognizing this imperative, WHO developed guidelines on management
of health complications of FGM. In this paper, based on foundational research for
the development of WHO's guidelines, we situate the practice of FGM as a rights
violation in the context of international and national policy and efforts, and
explore the role of health providers in upholding health-related human rights of
women at girls who are survivors, or who are at risk. Findings are based on a
literature review of relevant international human rights treaties and UN Treaty
Monitoring Bodies.
PMID- 28499387
TI - Evolution of the "fourth stage" of epidemiologic transition in people aged 80
years and over: population-based cohort study using electronic health records.
AB - BACKGROUND: In the "fourth stage" of epidemiological transition, the distribution
of non-communicable diseases is expected to shift to more advanced ages, but age
specific changes beyond 80 years of age have not been reported. METHODS: This
study aimed to evaluate demographic and health transitions in a population aged
80 years and over in the United Kingdom from 1990 to 2014, using primary care
electronic health records. Epidemiological analysis of chronic morbidities and
age-related impairments included a cohort of 299,495 participants, with
stratified sampling by five-year age group up to 100 years and over. Cause
specific proportional hazards models were used to estimate hazard ratios for
incidence rates over time. RESULTS: Between 1990 and 2014, nonagenarians and
centenarians increased as a proportion of the over-80 population, as did the male
to-female ratio among individuals aged 80 to 95 years. A lower risk of coronary
heart disease (HR 0.54, 95% confidence interval [CI]: 0.50-0.58), stroke (0.83,
0.76-0.90) and chronic obstructive pulmonary disease (0.59, 0.54-0.64) was
observed among 80-84 year-olds in 2010-2014 compared to 1995-1999. By contrast,
the risk of type II diabetes (2.18, 1.96-2.42), cancer (1.52, 1.43-1.61),
dementia (2.94, 2.70-3.21), cognitive impairment (5.57, 5.01-6.20), and
musculoskeletal pain (1.26, 1.21-1.32) was greater in 2010-2014 compared to 1995
1999. CONCLUSIONS: Redistribution of the over-80 population to older ages, and
declining age-specific incidence of cardiovascular and respiratory diseases in
over-80s, are consistent with the "fourth stage" of epidemiologic transition, but
increases in diabetes, cancer, and age-related impairment show new emerging
epidemiological patterns in the senior elderly.
PMID- 28499388
TI - Frequent use of hospital inpatient services during a nine year period: a
retrospective cohort study.
AB - BACKGROUND: Frequent use (FU) of hospital services impacts on patients and health
service expenditure. Studies examining FU in emergency departments and inpatient
settings have found heterogeneity and the need to differentiate between
potentially preventable FU and that associated with ongoing management of complex
conditions. Psychosocial factors have often been reported as underpinning or
exacerbating the phenomena. Most FU studies have been limited by time, to a
single study site, or restricted to specific diagnoses or patient groups. This
study provides a comprehensive description of adult patient characteristics,
conditions and risk factors associated with FU, based on admissions to the five
public hospitals in the Northern Territory (NT) of Australia over a nine year
period. The study population is distinctive comprising both Aboriginal and non
Aboriginal patients. METHODS: Data on all inpatient episodes in NT public
hospitals between 2005 and 2013 was analysed to identify patients with any FU
(four or more episodes within any 12-month period) and measure FU duration
(number of FU years) and intensity (mean number of episodes per FU year).
Pregnancy, alcohol-related and mental health condition flags were assigned to
patients with any episode with relevant diagnoses during the study period.
Multivariate analysis was used to assess factors associated with any FU, FU
duration and FU intensity, separately for Aboriginal and non-Aboriginal patients.
RESULTS: Of people with any inpatient episodes during the study period, 13.6%
were frequent users (Aboriginal 22%, non-Aboriginal 10%) accounting for 46.6% of
all episodes. 73% of frequent users had only one FU year. Any FU and increased FU
duration were more common among individuals who were: Aboriginal; older; female;
and those with a pregnancy, alcohol or mental health flag. Having two or more
alcohol-related episodes in the nine-year period was strongly associated with any
FU for both Aboriginal (odds ratio 8.9, 95% CI. 8.20-9.66) and non-Aboriginal
patients (11.5, 9.92-13.26). CONCLUSION: For many people, frequent inpatient
treatment is necessary and unavoidable. This study suggests that damage arising
from excessive alcohol consumption (either personal or by others) is the single
most avoidable factor associated with FU, particularly for Aboriginal people.
PMID- 28499389
TI - A phase II trial of autologous dendritic cell vaccination and radiochemotherapy
following fluorescence-guided surgery in newly diagnosed glioblastoma patients.
AB - BACKGROUND: Prognosis of patients with glioblastoma multiforme (GBM) remains
dismal, with median overall survival (OS) of about 15 months. It is therefore
crucial to search alternative strategies that improve these results obtained with
conventional treatments. In this context, immunotherapy seems to be a promising
therapeutic option. We hypothesized that the addition of tumor lysate-pulsed
autologous dendritic cells (DCs) vaccination to maximal safe resection followed
by radiotherapy and concomitant and adjuvant temozolomide could improve patients'
survival. METHODS: We conducted a phase-II clinical trial of autologous DCs
vaccination in patients with newly diagnosed patients GBM who were candidates to
complete or near complete resection. Candidates were finally included if residual
tumor volume was lower than 1 cc on postoperative radiological examination.
Autologous DCs were generated from peripheral blood monocytes and pulsed with
autologous whole tumor lysate. The vaccination calendar started before
radiotherapy and was continued during adjuvant chemotherapy. Progression free
survival (PFS) and OS were analyzed with the Kaplan-Meier method. Immune response
were assessed in blood samples obtained before each vaccines. RESULTS: Thirty-two
consecutive patients were screened, one of which was a screening failure due to
insufficient resection. Median age was 61 years (range 42-70). Karnofsky
performance score (KPS) was 90-100 in 29%, 80 in 35.5% and 60-70 in 35.5% of
cases. MGMT (O6-methylguanine-DNA-methyltransferase) promoter was methylated in
45.2% of patients. No severe adverse effects related to immunotherapy were
registered. Median PFS was 12.7 months (CI 95% 7-16) and median OS was 23.4
months (95% CI 16-33.1). Increase in post-vaccination tumor specific immune
response after vaccines (proliferation or cytokine production) was detected in
11/27 evaluated patients. No correlation between immune response and survival was
found. CONCLUSIONS: Our results suggest that the addition of tumor lysate-pulsed
autologous DCs vaccination to tumor resection and combined radio-chemotherapy is
feasible and safe. A multicenter randomized clinical trial is warranted to
evaluate the potential survival benefit of this therapeutic approach. Trial
registration This phase-II trial was registered as EudraCT: 2009-009879-35 and
ClinicalTrials.gov Identifier: NCT01006044 retrospectively registered.
PMID- 28499390
TI - High-content behavioral profiling reveals neuronal genetic network modulating
Drosophila larval locomotor program.
AB - BACKGROUND: Two key questions in understanding the genetic control of behaviors
are: what genes are involved and how these genes interact. To answer these
questions at a systems level, we conducted high-content profiling of Drosophila
larval locomotor behaviors for over 100 genotypes. RESULTS: We studied 69 genes
whose C. elegans orthologs were neuronal signalling genes with significant
locomotor phenotypes, and conducted RNAi with ubiquitous, pan-neuronal, or motor
neuronal Gal4 drivers. Inactivation of 42 genes, including the nicotinic
acetylcholine receptors nAChRalpha1 and nAChRalpha3, in the neurons caused
significant movement defects. Bioinformatic analysis suggested 81 interactions
among these genes based on phenotypic pattern similarities. Comparing the worm
and fly data sets, we found that these genes were highly conserved in having
neuronal expressions and locomotor phenotypes. However, the genetic interactions
were not conserved for ubiquitous profiles, and may be mildly conserved for the
neuronal profiles. Unexpectedly, our data also revealed a possible motor-neuronal
control of body size, because inactivation of Rdl and Galphao in the motor
neurons reduced the larval body size. Overall, these data established a framework
for further exploring the genetic control of Drosophila larval locomotion.
CONCLUSIONS: High content, quantitative phenotyping of larval locomotor
behaviours provides a framework for system-level understanding of the gene
networks underlying such behaviours.
PMID- 28499391
TI - Safety of three different product doses in autologous chondrocyte implantation:
results of a prospective, randomised, controlled trial.
AB - BACKGROUND: This study was conducted to assess the efficacy and safety of the
three dose levels of the three-dimensional autologous chondrocyte implantation
product chondrosphere(r) in the treatment of cartilage defects (4-10 cm2) of knee
joints. We hereby report the safety results for a 36-month post-treatment
observation period. METHODS: This was a prospective phase II trial with a
clinical intervention comprising biopsy for culturing spheroids and their
subsequent administration (level of evidence: I). Patients' knee defects were
investigated by arthroscopy, and a cartilage biopsy was taken for culturing.
Patients were randomised, on a single-blind basis, to treatment at the dose
levels 3-7 (low), 10-30 (medium) or 40-70 (high) spheroids per square centimetre.
Assessment (adverse events, vital signs, electrocardiography, physical
examination, concomitant medication and laboratory values) took place 1.5, 3, 6,
12, 24 and 36 months after chondrocyte implantation. RESULTS: Seventy-five
patients were included and 73 treated. The incidence of adverse events, of
patients with adverse events and of patients with treatment-related adverse
events showed no relevant difference between the treatment groups. There were no
fatal adverse events, no adverse events led to premature withdrawal from the
trial and none led to permanent sequelae. Two patients experienced serious
adverse events considered related to the study treatment: arthralgia 2-3 years
after implantation and chondropathy 1 and 2 years after implantation.
CONCLUSIONS: The treatment with chondrosphere(r) was generally well tolerated. No
relationship was detected between any safety criteria and the dose level:
Differences between the dose groups in the incidence of any adverse events, and
in numbers of patients with treatment-related adverse events, were insubstantial.
TRIAL REGISTRATION: clinicaltrials.gov, NCT01225575 .
PMID- 28499392
TI - Experimental tumor growth of canine osteosarcoma cell line on chick embryo
chorioallantoic membrane (in vivo studies).
AB - The chick embryo chorioallantoic membrane (CAM) model is extensively used in
human medicine in preclinical oncological studies. The CAM model has several
advantages: low cost, simple experimental approach, time saving and following "3R
principles". Research has shown that the human osteosarcoma cell lines U2OS, MMNG
HOS, and SAOS can form tumors on the CAM. In veterinary medicine, this has been
described only for feline fibrosarcomas, feline mammary carcinomas and canine
osteosarcomas. However, in case of canine osteosarcomas, it has been shown that
only non-adherent osteosarcoma stem cells isolated from KTOSA5 and CSKOS cell
lines have the ability to form microtumors on the CAM after an incubation period
of 5 days, in contrast to adherent KTOSA5 and CSKOS cells. In the presented
study, we have proven that the commercial adherent canine osteosarcoma cell line
(D-17) can form vascularized tumors on the CAM after the incubation period of 10
days.
PMID- 28499393
TI - Reversing the pipeline? Implementing public health evidence-based guidance in
english local government.
AB - BACKGROUND: In the UK, responsibility for many public health functions was
transferred in 2013 from the National Health Service (NHS) to local government; a
very different political context and one without the NHS history of policy and
practice being informed by evidence-based guidelines. A problem this move
presented was whether evidence-based guidelines would be seen as relevant, useful
and implementable within local government. This study investigates three aspects
of implementing national evidence-based recommendations for public health within
a local government context: influences on implementation, how useful guidelines
are perceived to be and whether the linear evidence-guidelines-practice model is
considered relevant. METHODS: Thirty-one councillors, public health directors and
deputy directors and officers and other local government employees were
interviewed about their experiences implementing evidence-based guidelines.
Interviews were informed and analysed using a theoretical model of behaviour (COM
B; Capability, Opportunity, Motivation-Behaviour). RESULTS: Contextual issues
such as budget, capacity and political influence were important influences on
implementation. Guidelines were perceived to be of limited use, with concerns
expressed about recommendations being presented in the abstract, lacking
specificity and not addressing the complexity of situations or local variations.
Local evidence was seen as the best starting point, rather than evidence-based
guidance produced by the traditional linear 'evidence-guidelines-practice' model.
Local evidence was used to not only provide context for recommendations but also
replace recommendations when they conflicted with local evidence. CONCLUSIONS:
Local government users do not necessarily consider national guidelines to be fit
for purpose at local level, with the consequence that local evidence tends to
trump evidence-based guidelines. There is thus a tension between the traditional
model of guideline development and the needs of public health decision-makers and
practitioners working in local government. This tension needs to be addressed to
facilitate implementation. One way this might be achieved, and participants
supported this approach, would be to reverse or re-engineer the traditional
pipeline of guideline development by starting with local need and examples of
effective local practice rather than starting with evidence of effectiveness
synthesised from the international scientific literature. Alternatively, and
perhaps in addition, training about the relevance of research evidence should
become a routine for local government staff and councillors.
PMID- 28499394
TI - SAR1a promoter polymorphisms are not associated with fetal hemoglobin in patients
with sickle cell disease from Cameroon.
AB - BACKGROUND: Reactivation of adult hemoglobin (HbF) is currently a dominant
therapeutic approach to sickle cell disease (SCD). In this study, we have
investigated among SCD patients from Cameroon, the association of HbF level and
variants in the HU-inducible small guanosine triphosphate-binding protein,
secretion-associated and RAS-related (SAR1a) protein, previously shown to be
associated with HbF after HU treatment in African American SCD patients. RESULTS:
Only patients >5 years old were included; hemoglobin electrophoresis and a full
blood count were conducted upon arrival at the hospital. RFLP-PCR was used to
describe the HBB gene haplotypes and Gap PCR to investigate the 3.7 kb alpha
globin gene deletion. The iPLEX Gold Sequenom Mass Genotyping Array and cycle
sequencing were used for the genotyping of four selected SNPs in SAR1a
(rs2310991; rs4282891; rs76901216 and rs76901220). Genetic analysis was performed
using an additive genetic model, under a generalized linear regression framework.
484 patients were studied. No associations were observed between any of the
promoter variants and baseline HbF, clinical events or other hematological
indices. CONCLUSION: The results of this study could be explained by possible
population-specificity of some tagging genomic variants associated with HbF
production and illustrated the complexity of replicating HbF-promoting variants
association results across African populations.
PMID- 28499395
TI - Time course of blood lactate levels, inflammation, and mitochondrial function in
experimental sepsis.
AB - BACKGROUND: A decrease in blood lactate levels (Lac) >10% during the first hours
of resuscitation in sepsis is associated with better outcomes, but the mechanisms
are unclear. Our objective was to investigate the relationship between the time
course of Lac, inflammatory response, and mitochondrial respiration during
experimental sepsis. METHODS: Original data from two previously published studies
were reanalyzed. In cohort 1, pigs were randomized to be resuscitated for 48 h
starting at 6, 12, and 24 h, respectively, after fecal peritonitis induction (n =
8 each). Animals were categorized according to the decrease in Lac during the
first 6 h of resuscitation (early if >=10% [Lac >=10%] or late if <10% or
increased [Lac <10%]), and systemic hemodynamics, inflammatory parameters, and
mitochondrial function were compared between groups. In a second group of animals
with fecal peritonitis and 24 h of resuscitation (n = 16, cohort 2), abdominal
regional Lac exchange was measured, and animals were categorized according to the
decrease in Lac as in cohort 1. RESULTS: Overall mortality was 20% (4 of 20) in
the Lac >=10% group and 60% (12 of 20) in the Lac <10% group (p = 0.022). In
cohort 1, systemic hemodynamics were similar in the Lac >=10% (n = 13) and Lac
<10% (n = 11) groups. Plasma interleukin-6 levels increased during unresuscitated
sepsis and decreased during resusciation in both groups, but they were lower at
study end in the Lac >=10% group (p = 0.047). Complexes I and II maximal (state
3) and resting (state 4) isolated brain mitochondrial respiration at study end
was higher in the Lac >=10% group than in the Lac <10% group, whereas hepatic,
myocardial, and skeletal muscle mitochondrial respiration was similar in both
groups. In cohort 2, mesenteric, total hepatic, and renal blood flow at study end
was higher in the Lac >=10% group (n = 7) than in the Lac <10% group (n = 9),
despite similar cardiac output. Hepatic lactate influx and uptake in the Lac
>=10% group were approximately 1.5 and 3 times higher, respectively, than in the
Lac <10% group (p = 0.066 for both). CONCLUSIONS: A decrease in Lac >10% during
early resuscitation (6 h) after abdominal sepsis is associated with lower levels
of plasma interleukin-6 and improved brain but not hepatic or muscle
mitochondrial respiration. Blood flow redistribution to abdominal organs in
animals with early decrease in Lac concentrations increases the potential to both
deliver and extract Lac.
PMID- 28499396
TI - Averaging rotational landmarks during total knee arthroplasty reduces component
malrotation caused by femoral asymmetry.
AB - BACKGROUND: Femoral component malrotation is a common cause of patient
dissatisfaction after total knee arthroplasty. The sulcus line (SL) is more
accurate than Whiteside's line as it corrects for variation in the coronal
orientation of the groove. The hypothesis is that averaging the SL and posterior
condylar axis (PCA) will reduce femoral malrotation. METHODS: The component was
inserted at a position between the SL and PCA in 91 patients. An intraoperative
photograph was taken showing the landmarks. These were compared to the component
position achieved relative to the surgical epicondylar axis (SEA) on a
postoperative CT scan. The component position was compared to the position
achieved using the individual landmarks. RESULTS: Relative to the SEA, the final
component position was 0.6 degrees (SD 1.4 degrees , range -3.8 degrees to +4.0
degrees ), the coronally corrected SL position was -0.7 degrees (SD 2.3 degrees
, -5.5 degrees to +4.6 degrees ), the PCA position was 0.9 degrees (SD 1.9
degrees , -6.1 degrees to +5.0 degrees ). Averaging the landmarks significantly
decreased the variance of the component position compared to using the SL and PCA
individually. The number of outliers (>3 degrees from SEA) was also
significantly less (p < 0.05) for the average position (2/84) when each was
compared to the SL (16/84) and PCA (14/84) individually. In 21/84 (25%) of cases,
there was more than 4 degrees of divergence between the SL and PCA. CONCLUSIONS:
Averaging the SL and the PCA decreases femoral component malrotation. Femora are
frequently asymmetrical in the axial plane. Referencing posterior condyles alone
to set rotation is likely to cause high rates of patellofemoral malalignment.
PMID- 28499398
TI - Biomechanical evaluation of a novel dualplate fixation method for proximal
humeral fractures without medial support.
AB - BACKGROUND: Comminuted fractures of the proximal humerus are generally treated
with the locking plate system, and clinical results are satisfactory. However,
unstable support of the medial column results in varus malunion and screw
perforation. We designed a novel medial anatomical locking plate (MLP) to
directly support the medial column. Theoretically, the combined application of
locking plate and MLP (LPMP) would directly provide strong dual-column stability.
We hypothesized that the LPMP could provide greater construct stability than the
locking plate alone (LP), locking plate combined with a fibular graft (LPSG), and
locking plate combined with a distal radius plate (LPDP). METHODS: LP, LPMP,
LPSG, and LPDP implants were instrumented into the finite element model of a
proximal humeral fracture. Axial, shear, and rotational loads were applied to the
models under normal and osteoporotic bone conditions. The whole simulation was
repeated five times for each fixator. To assess the biomechanical
characteristics, the construct stiffness, fracture micromotion, stress
distribution, and neck-shaft angle (NSA) were compared. RESULTS: The LPMP group
showed significantly greater integral and regional construct stiffness, and
endured less von Mises stresses, than the other three fixation methods. The
stresses on the lateral locking plate were dispersed by the MLP. The LPMP group
showed the least change in NSA. CONCLUSIONS: From the finite element viewpoint,
the LPMP method provided both lateral and medial direct support. The LPMP system
was effective in treating proximal humeral fracture with an unstable medial
column.
PMID- 28499397
TI - Neutral Lipid Storage Diseases: clinical/genetic features and natural history in
a large cohort of Italian patients.
AB - BACKGROUND: A small number of patients affected by Neutral Lipid Storage Diseases
(NLSDs: NLSD type M with Myopathy and NLSD type I with Ichthyosis) have been
described in various ethnic groups worldwide. However, relatively little is known
about the progression and phenotypic variability of the disease in large specific
populations. The aim of our study was to assess the natural history, disability
and genotype-phenotype correlations in Italian patients with NLSDs. Twenty-one
patients who satisfied the criteria for NLSDs were enrolled in a retrospective
cross-sectional study to evaluate the genetic aspects, clinical signs at onset,
disability progression and comorbidities associated with this group of diseases.
RESULTS: During the clinical follow-up (range: 2-44 years, median: 17.8 years),
two patients (9.5%, both with NLSD-I) died of hepatic failure, and a further five
(24%) lost their ability to walk or needed help when walking after a mean period
of 30.6 years of disease. None of the patients required mechanical ventilation.
No patient required a heart transplant, one patient with NLSD-M was implanted
with a cardioverter defibrillator for severe arrhythmias. CONCLUSION: The
genotype/phenotype correlation analysis in our population showed that the same
gene mutations were associated with a varying clinical onset and course. This
study highlights peculiar aspects of Italian NLSD patients that differ from those
observed in Japanese patients, who were found to be affected by a marked
hypertrophic cardiopathy. Owing to the varying phenotypic expression of the same
mutations, it is conceivable that some additional genetic or epigenetic factors
affect the symptoms and progression in this group of diseases.
PMID- 28499399
TI - Identification of potential Campylobacter jejuni genes involved in biofilm
formation by EZ-Tn5 Transposome mutagenesis.
AB - BACKGROUND: Biofilm formation has been suggested to play a role in the survival
of Campylobacter jejuni in the environment and contribute to the high incidence
of human campylobacteriosis. Molecular studies of biofilm formation by
Campylobacter are sparse. RESULTS: We attempted to identify genes that may be
involved in biofilm formation in seven C. jejuni strains through construction of
mutants using the EZ-Tn5 Transposome system. Only 14 mutants with reduced biofilm
formation were obtained, all from one strain of C. jejuni. Three different genes
of interest, namely CmeB (synthesis of multidrug efflux system transporter
proteins), NusG (transcription termination and anti-termination protein) and a
putative transmembrane protein (involved in membrane protein function) were
identified. The efficiency of the EZ::TN5 transposon mutagenesis approach was
strain dependent and was unable to generate any mutants from most of the strains
used. CONCLUSIONS: A diverse range of genes may be involved in biofilm formation
by C. jejuni. The application of the EZ::TN5 system for construction of mutants
in different Campylobacter strains is limited.
PMID- 28499400
TI - EpiTEome: Simultaneous detection of transposable element insertion sites and
their DNA methylation levels.
AB - The genome-wide investigation of DNA methylation levels has been limited to
reference transposable element positions. The methylation analysis of non
reference and mobile transposable elements has only recently been performed, but
required both genome resequencing and MethylC-seq datasets. We have created
epiTEome, a program that detects both new transposable element insertion sites
and their methylation states from a single MethylC-seq dataset. EpiTEome
outperforms other split-read insertion site detection programs, even while
functioning on bisulfite-converted reads. EpiTEome characterizes the previously
discarded fraction of DNA methylation at sites of new insertions, enabling future
investigation into the epigenetic regulation of non-reference and transposed
elements.
PMID- 28499401
TI - Are general and strategic measures of organizational context and leadership
associated with knowledge and attitudes toward evidence-based practices in public
behavioral health settings? A cross-sectional observational study.
AB - BACKGROUND: Examining the role of modifiable barriers and facilitators is a
necessary step toward developing effective implementation strategies. This study
examines whether both general (organizational culture, organizational climate,
and transformational leadership) and strategic (implementation climate and
implementation leadership) organizational-level factors predict therapist-level
determinants of implementation (knowledge of and attitudes toward evidence-based
practices). METHODS: Within the context of a system-wide effort to increase the
use of evidence-based practices (EBPs) and recovery-oriented care, we conducted
an observational, cross-sectional study of 19 child-serving agencies in the City
of Philadelphia, including 23 sites, 130 therapists, 36 supervisors, and 22
executive administrators. Organizational variables included characteristics such
as EBP initiative participation, program size, and proportion of independent
contractor therapists; general factors such as organizational culture and climate
(Organizational Social Context Measurement System) and transformational
leadership (Multifactor Leadership Questionnaire); and strategic factors such as
implementation climate (Implementation Climate Scale) and implementation
leadership (Implementation Leadership Scale). Therapist-level variables included
demographics, attitudes toward EBPs (Evidence-Based Practice Attitudes Scale),
and knowledge of EBPs (Knowledge of Evidence-Based Services Questionnaire). We
used linear mixed-effects regression models to estimate the associations between
the predictor (organizational characteristics, general and strategic factors) and
dependent (knowledge of and attitudes toward EBPs) variables. RESULTS: Several
variables were associated with therapists' knowledge of EBPs. Clinicians in
organizations with more proficient cultures or higher levels of transformational
leadership (idealized influence) had greater knowledge of EBPs; conversely,
clinicians in organizations with more resistant cultures, more functional
organizational climates, and implementation climates characterized by higher
levels of financial reward for EBPs had less knowledge of EBPs. A number of
organizational factors were associated with the therapists' attitudes toward
EBPs. For example, more engaged organizational cultures, implementation climates
characterized by higher levels of educational support, and more proactive
implementation leadership were all associated with more positive attitudes toward
EBPs. CONCLUSIONS: This study provides evidence for the importance of both
general and strategic organizational determinants as predictors of knowledge of
and attitudes toward EBPs. The findings highlight the need for longitudinal and
mixed-methods studies that examine the influence of organizational factors on
implementation.
PMID- 28499402
TI - ERK signaling is required for VEGF-A/VEGFR2-induced differentiation of porcine
adipose-derived mesenchymal stem cells into endothelial cells.
AB - BACKGROUND: Cell-based therapy that can rejuvenate the endothelium with
stimulated adipose-derived mesenchymal stem cells (AMSCs) is a promising
therapeutic strategy for the re-endothelialization of denuded arteries at the
stenting site. Previously, we have shown that silencing of MMP-2 and MMP-14
inhibits vascular endothelial growth factor receptor type 2 (VEGFR2) cleavage,
and induces differentiation of AMSCs toward the endothelial cell (EC) lineage. In
this study, we examined the underlying signaling pathways that regulate
differentiation of AMSCs to ECs in vitro through VEGFR2. METHODS: AMSCs were
isolated from porcine abdominal adipose tissue. The isolated AMSCs were
characterized by positive expression of CD29, CD44, and CD90 and negative
expression of CD11b and CD45. The isolated MSCs were transfected with siRNA to
silence MMP-2, MMP-14, and angiotensin receptor 2 (ATR2). Cells were suspended
either in endothelial basal media (EBM) or endothelial growth media (EGM) with
various treatments. Flow cytometry was performed to examine the expression of EC
markers, and western blot analysis was performed to examine the expression and
activity of various kinases. Scratch assay was performed to examine the cell
migration. Data were analyzed by ANOVA using PRISM GraphPad. RESULTS: After 10
days of stimulation for EC differentiation, the morphology of AMSCs changed to a
morphology similar to that of ECs. Silencing MMP-2 and MMP-14 resulted in
significant decrease in the number of migrated cells compared with the EGM-only
group. ATR2 siRNA transfection did not affect the migration and differentiation
of AMSCs to ECs. Stimulation of AMSCs for EC differentiation with or without MMP
2 or MMP-14 siRNA resulted in significant increase in p-ERK, and significant
decrease in p-JNK. There was no significant change in p-p38 in all three groups
compared with the EBM group. ERK inhibition resulted in significant decrease in
the expression of EC markers in the EGM, EGM + MMP-2 siRNA, and EGM + MMP-14
siRNA groups. The VEGFR2 kinase inhibitor induced a dose-dependent inhibition of
ERK. CONCLUSION: The ERK signaling pathway is critical for VEGF-A/VEGFR2-induced
differentiation of AMSCs into ECs. These findings provide new insights into the
role of the ERK signaling pathway in AMSC differentiation to ECs for potential
clinical use in cardiovascular diseases.
PMID- 28499403
TI - Surface displaying of swine IgG1 Fc enhances baculovirus-vectored vaccine
efficacy by facilitating viral complement escape and mammalian cell transduction.
AB - Baculovirus-mediated gene transfer has been developed as a vaccine design
strategy against a number of diseases without apparent viral replication.
However, it has been hampered by complement-dependent inactivation, thus
hindering the in vivo application of baculovirus. A variety of approaches have
been exploited to bypass the complement system in the serum. In this study, we
constructed and screened a series of baculovirus vectors displaying complement
interfering factors, of which a baculovirus vector displaying swine IgG1 Fc (pFc)
showed the highest complement antagonism (75.6%). Flow cytometry analysis of
transduced cells demonstrated that the baculovirus display of pFc had a
significant increase in transduction efficiency and transgene expression of
reporter genes. On this basis, a VSV-G-pseudotyped with swine IgG1 Fc surface
displayed baculovirus vector was developed to express the classical swine fever
virus (CSFV) E2 gene. The translational enhancers Syn21 and P10UTR were
incorporated to improve the antigen expression. The E2 gene was efficiently
expressed in both insect and mammalian cells. Pigs immunized with this
recombinant baculovirus developed high levels of E2-specific antibody, CSFV
specific neutralizing antibody and IFN-gamma-secreting cellular immune responses.
These results demonstrate that the strategy of surface-displaying swine IgG1 Fc
has a great potential to improve the efficiency of baculovirus-vectored vaccine
for CSFV and other swine pathogens.
PMID- 28499404
TI - Anterograde monosynaptic transneuronal tracers derived from herpes simplex virus
1 strain H129.
AB - BACKGROUND: Herpes simplex virus type 1 strain 129 (H129) has represented a
promising anterograde neuronal circuit tracing tool, which complements the
existing retrograde tracers. However, the current H129 derived tracers are
multisynaptic, neither bright enough to label the details of neurons nor capable
of determining direct projection targets as monosynaptic tracer. METHODS: Based
on the bacterial artificial chromosome of H129, we have generated a serial of
recombinant viruses for neuronal circuit tracing. Among them, H129-G4 was
obtained by inserting binary tandemly connected GFP cassettes into the H129
genome, and H129-DeltaTK-tdT was obtained by deleting the thymidine kinase (TK)
gene and adding tdTomato coding gene to the H129 genome. Then the obtained viral
tracers were tested in vitro and in vivo for the tracing capacity. RESULTS: H129
G4 is capable of transmitting through multiple synapses, labeling the neurons by
green florescent protein, and visualizing the morphological details of the
labeled neurons. H129-DeltaTK-tdT neither replicates nor spreads in neurons
alone, but transmits to and labels the postsynaptic neurons with tdTomato in the
presence of complementary expressed TK from a helper virus. H129-DeltaTK-tdT is
also capable to map the direct projectome of the specific neuron type in the
given brain regions in Cre transgenic mice. In the tested brain regions where
circuits are well known, the H129-DeltaTK-tdT tracing patterns are consistent
with the previous results. CONCLUSIONS: With the assistance of the helper virus
complimentarily expressing TK, H129-DeltaTK-tdT replicates in the initially
infected neuron, transmits anterogradely through one synapse, and labeled the
postsynaptic neurons with tdTomato. The H129-DeltaTK-tdT anterograde monosynaptic
tracing system offers a useful tool for mapping the direct output in neuronal
circuitry. H129-G4 is an anterograde multisynaptic tracer with a labeling signal
strong enough to display the details of neuron morphology.
PMID- 28499405
TI - A comparative molecular and 3-dimensional structural investigation into cross
continental and novel avian Trypanosoma spp. in Australia.
AB - BACKGROUND: Molecular and structural information on avian Trypanosoma spp.
throughout Australia is limited despite their intrinsic value in understanding
trypanosomatid evolution, diversity, and structural biology. In Western Australia
tissue samples (n = 429) extracted from 93 birds in 25 bird species were screened
using generic PCR primers to investigate the diversity of Trypanosoma spp. To
investigate avian trypanosome structural biology the first 3-dimensional
ultrastructural models of a Trypanosoma spp. (Trypanosoma sp. AAT) isolated from
a bird (currawong, Strepera spp.) were generated using focussed ion beam milling
combined with scanning electron microscopy (FIB-SEM). RESULTS: Here, we confirm
four intercontinental species of avian trypanosomes in native Australian birds,
and identify a new avian Trypanosoma. Trypanosome infection was identified in 18
birds from 13 different bird species (19%). A single new genotype was isolated
and found to be closely related to T. culicavium (Trypanosoma sp. CC2016 B002).
Other Trypanosoma spp. identified include T. avium, T. culicavium, T.
thomasbancrofti, Trypanosoma sp. TL.AQ.22, Trypanosoma sp. AAT, and an
uncharacterised Trypanosoma sp. (group C-III sensu Zidkova et al. (Infect Genet
Evol 12:102-112, 2012)), all previously identified in Australia or other
continents. Serially-sectioning Trypanosoma sp. AAT epimastigotes using FIB-SEM
revealed the disc-shaped kinetoplast pocket attached perpendicular to the
branching mitochondrion. Additionally, the universal minicircle sequence within
the kinetoplast DNA and the associated binding protein were determined in
Trypanosoma sp. AAT. CONCLUSIONS: These results indicate that bird trypanosomes
are relatively conserved across continents, while being locally diverse, which
supports the hypothesis that bird trypanosomes exist as fewer species than
described in the literature. Evidence exists that avian Trypanosoma spp. are
infecting mammals and could be transmitted by haemadipsid leeches. Trypanosoma
sp. AAT is most likely a separate species currently found only in Australia and
the first 3-dimentional ultrastructural analysis of an avian trypanosome provides
interesting information on their morphology and organelle arrangement.
PMID- 28499406
TI - Cattle genome-wide analysis reveals genetic signatures in trypanotolerant N'Dama.
AB - BACKGROUND: Indigenous cattle in Africa have adapted to various local
environments to acquire superior phenotypes that enhance their survival under
harsh conditions. While many studies investigated the adaptation of overall
African cattle, genetic characteristics of each breed have been poorly studied.
RESULTS: We performed the comparative genome-wide analysis to assess evidence for
subspeciation within species at the genetic level in trypanotolerant N'Dama
cattle. We analysed genetic variation patterns in N'Dama from the genomes of 101
cattle breeds including 48 samples of five indigenous African cattle breeds and
53 samples of various commercial breeds. Analysis of SNP variances between cattle
breeds using wMI, XP-CLR, and XP-EHH detected genes containing N'Dama-specific
genetic variants and their potential associations. Functional annotation analysis
revealed that these genes are associated with ossification, neurological and
immune system. Particularly, the genes involved in bone formation indicate that
local adaptation of N'Dama may engage in skeletal growth as well as immune
systems. CONCLUSIONS: Our results imply that N'Dama might have acquired distinct
genotypes associated with growth and regulation of regional diseases including
trypanosomiasis. Moreover, this study offers significant insights into
identifying genetic signatures for natural and artificial selection of diverse
African cattle breeds.
PMID- 28499407
TI - Early neurosyphilis presenting with facial palsy and an oral ulcer in a patient
who is human immunodeficiency virus positive: a case report.
AB - BACKGROUND: Neurosyphilis is the tertiary stage of Treponema pallidum infection
that involves the central nervous system, which occurs within days or weeks after
an initial syphilis infection, especially in immunocompromised patients. The
diagnosis of neurosyphilis is quite challenging as it is uncommon and often
presents with obscure symptoms since any organ system may be involved. CASE
PRESENTATION: We describe a case of a 40-year-old African man who is human
immunodeficiency virus positive with early neurosyphilis who presented with a
stiff neck, headache, confusion, restlessness, and a left-sided chest pain; he
did not respond to an empiric treatment of ceftriaxone and fluconazole for
meningitis, and tramadol for headache. Ten days after admission, he developed
generalized tonic-clonic convulsions; on examination he had ipsilateral facial
nerve palsy and an oral ulcer, and responded well to benzathine penicillin
treatment. CONCLUSIONS: Laboratory diagnosis of neurosyphilis is challenging
because to date there is no single laboratory test which is considered sensitive
enough for diagnosis of the disease, especially in resource-limited settings.
Clinical judgment is still an important part of diagnosis; and neurosyphilis
should be considered a diagnostic differential in patients with Human
Immunodeficiency Virus presenting with central nervous system involvement and in
other high-risk patients.
PMID- 28499409
TI - In your face: the biased judgement of fear-anger expressions in violent
offenders.
AB - BACKGROUND: Why is it that certain violent criminals repeatedly find themselves
engaged in brawls? Many inmates report having felt provoked or threatened by
their victims, which might be due to a tendency to ascribe malicious intentions
when faced with ambiguous social signals, termed hostile attribution bias.
METHODS: The present study presented morphed fear-anger faces to prison inmates
with a history of violent crimes, a history of child sexual abuse, and to matched
controls form the general population. Participants performed a fear-anger
decision task. Analyses compared both response frequencies and measures derived
from psychophysical functions fitted to the data. In addition, a test to
distinguish basic facial expressions and questionnaires for aggression,
psychopathy and personality disorders were administered. RESULTS: Violent
offenders present with a reliable hostile attribution bias, in that they rate
ambiguous fear-anger expressions as more angry, compared to both the control
population and perpetrators of child sexual abuse. Psychometric functions show a
lowered threshold to detect anger in violent offenders compared to the general
population. This effect is especially pronounced for male faces, correlates with
self-reported aggression and presents in absence of a general emotion recognition
impairment. CONCLUSIONS: The results indicate that a hostile attribution, related
to individual level of aggression and pronounced for male faces, might be one
mechanism mediating physical violence.
PMID- 28499408
TI - Organizational theory for dissemination and implementation research.
AB - BACKGROUND: Even under optimal internal organizational conditions, implementation
can be undermined by changes in organizations' external environments, such as
fluctuations in funding, adjustments in contracting practices, new technology,
new legislation, changes in clinical practice guidelines and recommendations, or
other environmental shifts. Internal organizational conditions are increasingly
reflected in implementation frameworks, but nuanced explanations of how
organizations' external environments influence implementation success are lacking
in implementation research. Organizational theories offer implementation
researchers a host of existing, highly relevant, and heretofore largely untapped
explanations of the complex interaction between organizations and their
environment. In this paper, we demonstrate the utility of organizational theories
for implementation research. DISCUSSION: We applied four well-known
organizational theories (institutional theory, transaction cost economics,
contingency theories, and resource dependency theory) to published descriptions
of efforts to implement SafeCare, an evidence-based practice for preventing child
abuse and neglect. Transaction cost economics theory explained how frequent,
uncertain processes for contracting for SafeCare may have generated
inefficiencies and thus compromised implementation among private child welfare
organizations. Institutional theory explained how child welfare systems may have
been motivated to implement SafeCare because doing so aligned with expectations
of key stakeholders within child welfare systems' professional communities.
Contingency theories explained how efforts such as interagency collaborative
teams promoted SafeCare implementation by facilitating adaptation to child
welfare agencies' internal and external contexts. Resource dependency theory
(RDT) explained how interagency relationships, supported by contracts, memoranda
of understanding, and negotiations, facilitated SafeCare implementation by
balancing autonomy and dependence on funding agencies and SafeCare developers. In
addition to the retrospective application of organizational theories demonstrated
above, we advocate for the proactive use of organizational theories to design
implementation research. For example, implementation strategies should be
selected to minimize transaction costs, promote and maintain congruence between
organizations' dynamic internal and external contexts over time, and
simultaneously attend to organizations' financial needs while preserving their
autonomy. We describe implications of applying organizational theory in
implementation research for implementation strategies, the evaluation of
implementation efforts, measurement, research design, theory, and practice. We
also offer guidance to implementation researchers for applying organizational
theory.
PMID- 28499410
TI - Comparison of the acute ocular manifestations of Stevens-Johnson syndrome and
toxic epidermal necrolysis in Chinese eyes: a 15-year retrospective study.
AB - BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
are rare but life-threatening conditions that initially affect the skin and
mucous membranes. The aim of this study was to compare the acute ocular
manifestations between SJS and TEN. METHODS: The initial presenting ophthalmic
records of patients with either SJS (<30% body surface area involvement) or TEN
(> = 30% involvement), who were treated at one tertiary burn center in Hong Kong
between 1999 and 2014, were retrospectively analyzed and compared. RESULTS: A
total of 20 SJS and 12 TEN cases were included. All were drug-induced. The
patient demographics and treatment received were comparable. Overall, 40% of SJS
and 75% of TEN patients had acute ocular surface inflammation. When comparing the
two groups, there was a significant difference in the number of cases with mild
involvement (5% in SJS, 42% in TEN, p = 0.01), while no statistically significant
differences were found (p > 0.05) comparing between the moderate (15% in SJS, 0%
in TEN) and severe groups (20% in SJS, 33% in TEN). CONCLUSIONS: Ocular surface
inflammation was common during the acute phase in both SJS and TEN. TEN had a
significantly higher number of cases with mild ocular involvement when compared
with SJS, but no significant difference between the number of moderate and severe
cases between the two groups.
PMID- 28499411
TI - Paraneoplastic acral vascular syndrome in a patient with metastatic melanoma
under immune checkpoint blockade.
AB - BACKGROUND: Paraneoplastic acral vascular syndrome (PAVS) is a rare phenomenon
which is observed in patients with adenocarcinomas and other malignancies.
Various potential pathogenic mechanisms such as tumour invasion of sympathetic
nerves, hyperviscosity, hypercoagulability, vasoactive tumour-secreted
substances, and immunological mechanisms have been suggested. CASE PRESENTATION:
We report a 60-year-old Caucasian male attended our hospital with a bulky lymph
node mass in the right axilla. Extirpation of a lymph node conglomerate revealed
5 melanoma lymph node metastases. Computed tomography showed a liver metastasis
(diameter: 3.8 cm), several retroperitoneal metastases, bilateral metastases in
the lung hilus, and prepectoral subcutaneous metastases (Stage IV; pTx, N3, M1c).
Lactate dehydrogenase and S100B were slightly elevated. Combination therapy of
nivolumab (1 mg/kg BW) and ipilimumab (3 mg/kg BW) was started. Three weeks after
the first combination therapy he developed progressive erythema, paraesthesia and
pain on the fingertips of both hands. Both cold and warmth was not well tolerated
by the patient. Complete work-up excluded associated conditions or factors such
as haematological disorders, rheumatologic disorders, hypertension, diabetes or
smoking. Treatment was initiated with prostacyclin 20 MUg twice daily and oral
prednisolone 50 mg in tapering dosage. However, prostacyclin was stopped after
the first applications because the pain increased during infusion. The second
course of nivolumab and ipilimumab was administered. About 2 weeks later, the
patient presented with increased pain and small subungual necrosis. We treated
the patient with oral analgetics and intravenous prednisolone 500 mg in tapering
dosage. On digital substraction angiography occlusion of all arteries of the
fingers was demonstrated. Further rheologic and anti-melanoma treatments were
refused by the patient. About 2 months after the second course of nivolumab and
ipilimumab combination therapy several fingers showed severe gangrene which
finally led to amputations of end phalanges of several fingers. Histopathology
did not reveal evidence for vasculitis or other primary vascular pathologies.
During the following 2 months the patient experienced dramatic progress of his
metastatic disease and finally died at multi-organ failure. CONCLUSION: Presence
of rapidly progressive digital ischemia in an elderly patient with cancer should
always raise clinical suspicion of a paraneoplastic phenomenon when other
possible causes have been excluded. In patients treated with immune checkpoint
inhibitors such as CTLA-4 and PD-L1 blockers PVAS-like events have not been
reported so far. However, it is debatable whether immune checkpoint blockade may
play a pathogenetic role in the development of PAVS in patients with
malignancies.
PMID- 28499412
TI - Genome-wide DNA methylation analysis reveals hypomethylation in the low-CpG
promoter regions in lymphoblastoid cell lines.
AB - BACKGROUND: Epidemiological studies of DNA methylation profiles may uncover the
molecular mechanisms through which genetic and environmental factors contribute
to the risk of multifactorial diseases. There are two types of commonly used DNA
bioresources, peripheral blood cells (PBCs) and EBV-transformed lymphoblastoid
cell lines (LCLs), which are available for genetic epidemiological studies.
Therefore, to extend our knowledge of the difference in DNA methylation status
between LCLs and PBCs is important in human population studies that use these DNA
sources to elucidate the epigenetic risks for multifactorial diseases. We
analyzed the methylation status of the autosomes for 192 and 92 DNA samples that
were obtained from PBCs and LCLs, respectively, using a human methylation 450 K
array. After excluding SNP-associated methylation sites and low-call sites,
400,240 sites were subjected to analysis using a generalized linear model with
cell type, sex, and age as the independent variables. RESULTS: We found that the
large proportion of sites showed lower methylation levels in LCLs compared with
PBCs, which is consistent with previous reports. We also found that significantly
different methylation sites tend to be located on the outside of the CpG island
and in a region relatively far from the transcription start site. Additionally,
we observed that the methylation change of the sites in the low-CpG promoter
region was remarkable. Finally, it was shown that the correlation between the
chronological age and ageing-associated methylation sites in ELOVL2 and FHL2 in
the LCLs was weaker than that in the PBCs. CONCLUSIONS: The methylation levels of
highly methylated sites of the low-CpG-density promoters in PBCs decreased in the
LCLs, suggesting that the methylation sites located in low-CpG-density promoters
could be sensitive to demethylation in LCLs. Despite being generated from a
single cell type, LCLs may not always be a proxy for DNA from PBCs in studies of
epigenome-wide analysis attempting to elucidate the role of epigenetic change in
disease risks.
PMID- 28499413
TI - Ranking metrics in gene set enrichment analysis: do they matter?
AB - BACKGROUND: There exist many methods for describing the complex relation between
changes of gene expression in molecular pathways or gene ontologies under
different experimental conditions. Among them, Gene Set Enrichment Analysis seems
to be one of the most commonly used (over 10,000 citations). An important
parameter, which could affect the final result, is the choice of a metric for the
ranking of genes. Applying a default ranking metric may lead to poor results.
METHODS AND RESULTS: In this work 28 benchmark data sets were used to evaluate
the sensitivity and false positive rate of gene set analysis for 16 different
ranking metrics including new proposals. Furthermore, the robustness of the
chosen methods to sample size was tested. Using k-means clustering algorithm a
group of four metrics with the highest performance in terms of overall
sensitivity, overall false positive rate and computational load was established
i.e. absolute value of Moderated Welch Test statistic, Minimum Significant
Difference, absolute value of Signal-To-Noise ratio and Baumgartner-Weiss
Schindler test statistic. In case of false positive rate estimation, all selected
ranking metrics were robust with respect to sample size. In case of sensitivity,
the absolute value of Moderated Welch Test statistic and absolute value of Signal
To-Noise ratio gave stable results, while Baumgartner-Weiss-Schindler and Minimum
Significant Difference showed better results for larger sample size. Finally, the
Gene Set Enrichment Analysis method with all tested ranking metrics was
parallelised and implemented in MATLAB, and is available at
https://github.com/ZAEDPolSl/MrGSEA . CONCLUSIONS: Choosing a ranking metric in
Gene Set Enrichment Analysis has critical impact on results of pathway enrichment
analysis. The absolute value of Moderated Welch Test has the best overall
sensitivity and Minimum Significant Difference has the best overall specificity
of gene set analysis. When the number of non-normally distributed genes is high,
using Baumgartner-Weiss-Schindler test statistic gives better outcomes. Also, it
finds more enriched pathways than other tested metrics, which may induce new
biological discoveries.
PMID- 28499414
TI - HLAscan: genotyping of the HLA region using next-generation sequencing data.
AB - BACKGROUND: Several recent studies showed that next-generation sequencing (NGS)
based human leukocyte antigen (HLA) typing is a feasible and promising technique
for variant calling of highly polymorphic regions. To date, however, no method
with sufficient read depth has completely solved the allele phasing issue. In
this study, we developed a new method (HLAscan) for HLA genotyping using NGS
data. RESULTS: HLAscan performs alignment of reads to HLA sequences from the
international ImMunoGeneTics project/human leukocyte antigen (IMGT/HLA) database.
The distribution of aligned reads was used to calculate a score function to
determine correctly phased alleles by progressively removing false-positive
alleles. Comparative HLA typing tests using public datasets from the 1000 Genomes
Project and the International HapMap Project demonstrated that HLAscan could
perform HLA typing more accurately than previously reported NGS-based methods
such as HLAreporter and PHLAT. In addition, the results of HLA-A, -B, and -DRB1
typing by HLAscan using data generated by NextGen were identical to those
obtained using a Sanger sequencing-based method. We also applied HLAscan to a
family dataset with various coverage depths generated on the Illumina HiSeq X-TEN
platform. HLAscan identified allele types of HLA-A, -B, -C, -DQB1, and -DRB1 with
100% accuracy for sequences at >= 90* depth, and the overall accuracy was 96.9%.
CONCLUSIONS: HLAscan, an alignment-based program that takes read distribution
into account to determine true allele types, outperformed previously developed
HLA typing tools. Therefore, HLAscan can be reliably applied for determination of
HLA type across the whole-genome, exome, and target sequences.
PMID- 28499415
TI - Discrimination of candidate subgenome-specific loci by linkage map construction
with an S1 population of octoploid strawberry (Fragaria * ananassa).
AB - BACKGROUND: The strawberry, Fragaria * ananassa, is an allo-octoploid (2n = 8x =
56) and outcrossing species. Although it is the most widely consumed berry crop
in the world, its complex genome structure has hindered its genetic and genomic
analysis, and thus discrimination of subgenome-specific loci among the
homoeologous chromosomes is needed. In the present study, we identified candidate
subgenome-specific single nucleotide polymorphism (SNP) and simple sequence
repeat (SSR) loci, and constructed a linkage map using an S1 mapping population
of the cultivar 'Reikou' with an IStraw90 Axiom(r) SNP array and previously
published SSR markers. RESULTS: The 'Reikou' linkage map consisted of 11,574 loci
(11,002 SNPs and 572 SSR loci) spanning 2816.5 cM of 31 linkage groups. The
11,574 loci were located on 4738 unique positions (bin) on the linkage map. Of
the mapped loci, 8999 (8588 SNPs and 411 SSR loci) showed a 1:2:1 segregation
ratio of AA:AB:BB allele, which suggested the possibility of deriving loci from
candidate subgenome-specific sequences. In addition, 2575 loci (2414 SNPs and 161
SSR loci) showed a 3:1 segregation of AB:BB allele, indicating they were derived
from homoeologous genomic sequences. Comparative analysis of the homoeologous
linkage groups revealed differences in genome structure among the subgenomes.
CONCLUSIONS: Our results suggest that candidate subgenome-specific loci are
randomly located across the genomes, and that there are small- to large-scale
structural variations among the subgenomes. The mapped SNPs and SSR loci on the
linkage map are expected to be seed points for the construction of
pseudomolecules in the octoploid strawberry.
PMID- 28499416
TI - Cardioprotective potential of N-acetyl cysteine against hyperglycaemia-induced
oxidative damage: a protocol for a systematic review.
AB - BACKGROUND: Hyperglycaemia-induced oxidative damage is a well-established factor
implicated in the development of diabetic cardiomyopathy (DCM) in diabetic
individuals. Some of the well-known characteristics of DCM include increased
myocardial left ventricular wall thickness and remodelling that result in reduced
cardiac efficiency. To prevent this, an increasing number of pharmacological
compounds such as N-acetyl cysteine (NAC) are explored for their antioxidant
properties. A few studies have shown that NAC can ameliorate hyperglycaemia
induced oxidative damage within the heart. Hence, the objective of this review is
to synthesise the available evidence pertaining to the cardioprotective role of
NAC against hyperglycaemia-induced oxidative damage and thus prevent DCM.
METHODS: This systematic review protocol will be reported in accordance with the
Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols
(PRISMA-P) 2015 statement. We will perform a comprehensive search on major
databases such as EMBASE, Cochrane Library, PubMed and Google scholar for
original research articles published from January 1960 to March 2017. We will
only report on literature that is available in English. Two authors will
independently screen for eligible studies using pre-defined criteria, and data
extraction will be done in duplicate. All discrepancies will be resolved by
consensus or consultation of a third reviewer. The quality of studies will be
checked using Cochrane Risk of Bias Assessment Tool and The Joanna Briggs
Institute (JBI) Critical Appraisal tools for non-randomised experimental studies.
Heterogeneity across studies will be assessed using the Cochrane Q statistic and
the inconsistency index (I 2). We will use the random effects model to calculate
a pooled estimate. DISCUSSION: Although several studies have shown that NAC can
ameliorate hyperglycaemia-induced oxidative damage within the heart, this
systematic review will be the first pre-registered synthesis of data to identify
the cardioprotective potential of NAC against hyperglycaemia-induced oxidative
damage. This result will help guide future research evaluating the
cardioprotective role of NAC against DCM and better identify possible mechanisms
of action for NAC to prevent oxidative damage with a diabetic heart. SYSTEMIC
REVIEW REGISTRATION: PROSPERO CRD42017055851 .
PMID- 28499418
TI - Early morning urine collection to improve urinary lateral flow LAM assay
sensitivity in hospitalised patients with HIV-TB co-infection.
AB - BACKGROUND: Urine LAM testing has been approved by the WHO for use in
hospitalised patients with advanced immunosuppression. However, sensitivity
remains suboptimal. We therefore examined the incremental diagnostic sensitivity
of early morning urine (EMU) versus random urine sampling using the Determine(r)
lateral flow lipoarabinomannan assay (LF-LAM) in HIV-TB co-infected patients.
METHODS: Consenting HIV-infected inpatients, screened as part of a larger
prospective randomized controlled trial, that were treated for TB, and could
donate matched random and EMU samples were included. Thus paired sample were
collected from the same patient, LF-LAM was graded using the pre-January 2014,
with grade 1 and 2 manufacturer-designated cut-points (the latter designated
grade 1 after January 2014). Single sputum Xpert-MTB/RIF and/or TB culture
positivity served as the reference standard (definite TB). Those treated for TB
but not meeting this standard were designated probable TB. RESULTS: 123 HIV
infected patients commenced anti-TB treatment and provided matched random and EMU
samples. 33% (41/123) and 67% (82/123) had definite and probable TB,
respectively. Amongst those with definite TB LF-LAM sensitivity (95%CI), using
the grade 2 cut-point, increased from 12% (5-24; 5/43) to 39% (26-54; 16/41) with
random versus EMU, respectively (p = 0.005). Similarly, amongst probable TB, LF
LAM sensitivity increased from 10% (5-17; 8/83) to 24% (16-34; 20/82) (p =
0.001). LF-LAM specificity was not determined. CONCLUSION: This proof of concept
study indicates that EMU could improve the sensitivity of LF-LAM in hospitalised
TB-HIV co-infected patients. These data have implications for clinical practice.
PMID- 28499417
TI - Genome-wide characterization and expression analyses of superoxide dismutase
(SOD) genes in Gossypium hirsutum.
AB - BACKGROUND: Superoxide dismutases (SODs) are a key antioxidant enzyme family,
which have been implicated in protecting plants against the toxic effects of
reactive oxygen species. Despite current studies have shown that the gene family
are involved in plant growth and developmental processes and biotic and abiotic
stress responses, little is known about its functional role in upland cotton.
RESULTS: In the present study, we comprehensively analyzed the characteristics of
the SOD gene family in upland cotton (Gossypium hirsutum). Based on their
conserved motifs, 18 GhSOD genes were identified and phylogenetically classified
into five subgroups which corroborated their classifications based on gene
structure patterns and subcellular localizations. The GhSOD sequences were
distributed at different densities across 12 of the 26 chromosomes. The conserved
domains, gene family evolution cis-acting elements of promoter regions and miRNA
mediated posttranscriptional regulation were predicted and analyzed. In addition,
the expression pattern of 18 GhSOD genes were tested in different tissues/organs
and developmental stages, and different abiotic stresses and abscisic acid, which
indicated that the SOD gene family possessed temporal and spatial specificity
expression specificity and may play important roles in reactive oxygen species
scavenging caused by various stresses in upland cotton. CONCLUSIONS: This study
describes the first genome-wide analysis of the upland cotton SOD gene family,
and the results will help establish a foundation for the further cloning and
functional verification of the GhSOD gene family during stress responses, leading
to crop improvement.
PMID- 28499419
TI - Across-proteome modeling of dimer structures for the bottom-up assembly of
protein-protein interaction networks.
AB - BACKGROUND: Deciphering complete networks of interactions between proteins is the
key to comprehend cellular regulatory mechanisms. A significant effort has been
devoted to expanding the coverage of the proteome-wide interaction space at
molecular level. Although a growing body of research shows that protein docking
can, in principle, be used to predict biologically relevant interactions, the
accuracy of the across-proteome identification of interacting partners and the
selection of near-native complex structures still need to be improved. RESULTS:
In this study, we developed a new method to discover and model protein
interactions employing an exhaustive all-to-all docking strategy. This approach
integrates molecular modeling, structural bioinformatics, machine learning, and
functional annotation filters in order to provide interaction data for the bottom
up assembly of protein interaction networks. Encouragingly, the success rates for
dimer modeling is 57.5 and 48.7% when experimental and computer-generated monomer
structures are employed, respectively. Further, our protocol correctly identifies
81% of protein-protein interactions at the expense of only 19% false positive
rate. As a proof of concept, 61,913 protein-protein interactions were confidently
predicted and modeled for the proteome of E. coli. Finally, we validated our
method against the human immune disease pathway. CONCLUSIONS: Protein docking
supported by evolutionary restraints and machine learning can be used to reliably
identify and model biologically relevant protein assemblies at the proteome
scale. Moreover, the accuracy of the identification of protein-protein
interactions is improved by considering only those protein pairs co-localized in
the same cellular compartment and involved in the same biological process. The
modeling protocol described in this communication can be applied to detect
protein-protein interactions in other organisms and pathways as well as to
construct dimer structures and estimate the confidence of protein interactions
experimentally identified with high-throughput techniques.
PMID- 28499420
TI - Continuous femoral nerve blockade and single-shot sciatic nerve block promotes
better analgesia and lower bleeding for total knee arthroplasty compared to
intrathecal morphine: a randomized trial.
AB - BACKGROUND: Knee arthroplasty leads to postoperative pain. This study compares
analgesia and postoperative bleeding achieved by intrathecal morphine with a
continuous femoral plus single-shot sciatic nerve block. METHODS: A randomized
non-blinded clinical trial enrolled patients aged over 18 years old, ASA I to III
who underwent total knee arthroplasty. All patients underwent spinal anesthesia
with isobaric bupivacaine, 20 mg. One group received 100 mcg of intrathecal
morphine (M group), and the other received a femoral nerve block by continuous
infusion plus a "single shot" block of the sciatic nerve at the end of the
surgery (FI group). Pain score from verbal numeric rating scale (VNRS) and
morphine consumption during the first 72 h, as well as motor blockade, adverse
effects, and postoperative bleeding were recorded. Analysis of variance of
repeated measures with Bonferroni post-test, t-test and Fisher exact test were
used for statistical analysis. RESULTS: Thirty nine patients completed the study
(M = 20; FI = 19 patients) and were similar except for higher age in the FI
group. Motor blockade as well as movement pain during postanesthesia care unit
(PACU) staying were not different between the groups, but movement pain was
significantly lower in FI group after 24 h. Postoperative bleeding (ml) was lower
in FI group. CONCLUSIONS: Continuous femoral nerve block combined with sciatic
nerve block provides effective for postoperative analgesia in patients undergoing
total knee arthroplasty, with lower pain scores after 24 h and a lower incidence
of adverse effects and bleeding compared to intrathecal morphine. TRIAL
REGISTRATION: Retrospectively registered on https://clinicaltrials.gov/ under
identifier NCT02882152 , 23rd December, 2016.
PMID- 28499421
TI - Patterns of use and appropriateness of antibiotics prescribed to patients
receiving haemodialysis: an observational study.
AB - BACKGROUND: There are limited published data on the types and appropriateness of
oral and intravenous (IV) antibiotics prescribed to patients receiving
haemodialysis. This information is critical to optimise antibiotic prescribing.
Therefore this study aims to describe the patterns of use and the appropriateness
of oral and IV antibiotics prescribed to patients receiving haemodialysis.
METHODS: This was a prospective, observational study across four community and
two hospital inpatient haemodialysis units in Melbourne, Australia. Data were
collected from July 2014 to January 2015 from participants. Antibiotic regimens
prescribed were compared with nationally available antibiotic guidelines and then
classified as being either appropriate, inappropriate or not assessable by an
expert multidisciplinary team using the National Antimicrobial Prescribing Survey
tool. RESULTS: Overall, 114 participants consented to this study where 55.3%
(63/114) received antibiotics and 235 antibiotic regimens were prescribed at a
rate of 69.1 antibiotic regimens/100 patient-months. The most common oral
antibiotics prescribed were amoxycillin/clavulanic acid and cephalexin. The most
common IV antibiotics prescribed were vancomycin, piperacillin/tazobactam,
cephazolin and ceftriaxone. The percentage of inappropriate antibiotic regimens
prescribed were 34.9% (15/43) in the community setting and 22.1% (40/181) in the
hospital setting. Furthermore, 29.4% (30/102) of oral and 20.5% (25/122) of IV
antibiotic regimens were inappropriate with incorrect dosing as the primary
reason. CONCLUSION: Although this study is limited by the sample size, it
describes the high antibiotic exposure that patients receiving haemodialysis
experience. Of concern is inappropriate dose and frequency being a major issue.
This requires interventions focused on the quality use of medicines and
antimicrobial stewardship aspects of prescribing in this population.
PMID- 28499422
TI - Identification of novel genes associated with HIV-1 latency by analysis of
histone modifications.
AB - BACKGROUND: A reservoir of HIV-1 is a major obstacle in eliminating HIV-1 in
patients because it can reactivate in stopping antiretroviral therapy (ART).
Histone modifications, such as acetylation and methylation, play a critical role
in the organization of chromatin domains and the up- or downregulation of gene
expression. Although many studies have reported that an epigenetic mechanism is
strongly involved in the maintenance of HIV-1 transcriptional latency, neither
the epigenetic control of viral replication nor how HIV-1 latency is maintained
is not fully understood. RESULTS: We re-analyzed a high throughput parallel DNA
sequencing (ChIP-seq) data from previous work to investigate the effect of
histone modifications, H3K4me3 and H3K9ac, on HIV-1 latency in terms of
chromosome distribution. The outputs of ChIP-seq from uninfected CD4+ T cell
lines and HIV-1 latently infected cells were aligned to hg18 using bowtie and
then analyzed using various software packages. Certain chromosomes (16, 17, 19,
and 22) were significantly enriched for histone modifications in both decreased
and increased islands. In the same chromosomes in HIV-1 latently infected cells,
38 decreased and 41 increased islands from common islands of H3K4me3 and H3K9ac
were selected for functional annotation. In Gene Ontology analysis, the 38 genes
associated with decreased islands were involved in the regulation of biological
process, regulation of cellular process, biological regulation, and purinergic
receptor signaling pathway, while the 41 genes associated with increased islands
were involved in nucleic acid binding, calcium-activated cation channel activity,
DNA binding, and zinc ion binding. In Pathway Commons analysis, the 38 genes were
strongly involved in the p63 transcription factor network, while the 41 genes
were involved in the RNA polymerase III transcription termination pathway.
Several genes such as Nuclear factor I X (NFIX) and TNF receptor association
factor 4 (TRAF4) were selected as candidate genes for HIV latency. Especially,
NFIX was highly expressed in HIV-1 latently infected cell lines and showed a
dramatic reduction in expression after phorbol-13-myristate-12-acetate (PMA)
treatment. CONCLUSIONS: These results show that the unique enrichment of histone
modifications and its linked genes in specific chromosomes might play a critical
role in the establishment and maintenance of HIV-1 latency.
PMID- 28499423
TI - Could cash and good parenting affect child cognitive development? A cross
sectional study in South Africa and Malawi.
AB - BACKGROUND: Social protection interventions, including cash grants and care
provision have been shown to effectively reduce some negative impacts of the HIV
epidemic on adolescents and families. Less is known about the role of social
protection on younger HIV affected populations. This study explored the impact of
cash grants on children's cognitive development. Additionally, we examined
whether combined cash and care (operationalised as good parenting) was associated
with improved cognitive outcomes. METHODS: The sample included 854 children, aged
5 - 15, participating in community-based organisation (CBO) programmes for
children affected by HIV in South Africa and Malawi. Data on child cognitive
functioning were gathered by a combination of caregiver report and observer
administered tests. Primary caregivers also reported on the economic situation of
the family, cash receipt into the home, child and household HIV status. Parenting
was measured on a 10 item scale with good parenting defined as a score of 8 or
above. RESULTS: About half of families received cash (55%, n = 473), only 6% (n =
51) reported good parenting above the cut-off point but no cash, 18% (n = 151)
received combined cash support and reported good parenting, and 21% (n = 179) had
neither. Findings show that cash receipt was associated with enhanced child
cognitive outcomes in a number of domains including verbal working memory,
general cognitive functioning, and learning. Furthermore, cash plus good
parenting provided an additive effect. Child HIV status had a moderating effect
on the association between cash or/plus good parenting and cognitive outcomes.
The association between cash and good parenting and child cognitive outcomes
remained significant among both HIV positive and negative children, but overall
the HIV negative group benefited more. CONCLUSIONS: This study shows the
importance of cash transfers and good parenting on cognitive development of young
children living in HIV affected environments. Our data clearly indicate that
combined provision (cash plus good parenting) have added value.
PMID- 28499424
TI - Ultrastructural deposits appearing as "zebra bodies" in renal biopsy: Fabry
disease?- comparative case reports.
AB - BACKGROUND: Fabry Disease (FD) is a genetic disorder caused by alpha
galactosidase A deficiency. Certain drugs, such as hydroxychloroquine, can
produce renal deposits that mimic morphological findings seen in FD,
characterizing a type of drug-induced renal phospholipidosis. CASE PRESENTATION:
Case 1: A 28-year-old female patient with systemic lupus erythematosus who had
been using hydroxychloroquine for 14 months presented subnephrotic proteinuria.
Renal biopsy showed deposits compatible with FD. Neither activity analysis of
alpha-galactosidase A nor genetic analysis were available and were not performed.
These deposits were not detected in a subsequent renal biopsy three years after
withdrawal of the medication, characterizing a possible hydroxychloroquine
induced renal phospholipidosis. Case 2: A 29-year-old male patient presented with
acroparesthesia, angiokeratomas, cornea verticillata and subnephrotic
proteinuria. Deposits compatible with FD were detected upon renal biopsy. The
evaluation of alpha-galactosidase A showed no activity in both blood and
leukocytes. Genetic analysis identified an M284 T mutation in exon 6, and such
mutation was also found in other family members. CONCLUSION: Clinical
investigation is necessary in suspected cases of Fabry Disease upon renal biopsy
in order to confirm diagnosis. Drug-induced renal phospholipidosis should be
considered in differential diagnosis in cases with intracellular osmiophilic,
lamellar inclusions in electron microscopy.
PMID- 28499426
TI - Erratum to: Oral intake of a combination of glucosyl hesperidin and caffeine
elicits an antiobesity effect in healthy, moderately obese subjects: a randomized
double-blind placebo-controlled trial.
PMID- 28499425
TI - Hand-held cell phone use while driving legislation and observed driver behavior
among population sub-groups in the United States.
AB - BACKGROUND: Cell phone use behaviors are known to vary across demographic sub
groups and geographic locations. This study examined whether universal hand-held
calling while driving bans were associated with lower road-side observed hand
held cell phone conversations across drivers of different ages (16-24, 25-59,
>=60 years), sexes, races (White, African American, or other), ruralities
(suburban, rural, or urban), and regions (Northeast, Midwest, South, and West).
METHODS: Data from the 2008-2013 National Occupant Protection Use Survey were
merged with states' cell phone use while driving legislation. The exposure was
presence of a universal hand-held cell phone ban at time of observation. Logistic
regression was used to assess the odds of drivers having a hand-held cell phone
conversation. Sub-groups differences were assessed using models with interaction
terms. RESULTS: When universal hand-held cell phone bans were effective, hand
held cell phone conversations were lower across all driver demographic sub-groups
and regions. Sub-group differences existed among the sexes (p-value, <0.0001) and
regions (p-value, 0.0003). Compared to states without universal hand-held cell
phone bans, the adjusted odds ratio (aOR) of a driver hand-held phone
conversation was 0.34 [95% confidence interval (CI): 0.28, 0.41] for females
versus 0.47 (CI 0.40, 0.55) for males and 0.31 (CI 0.25, 0.38) for drivers in
Western states compared to 0.47 (CI 0.30, 0.72) in the Northeast and 0.50 (CI
0.38, 0.66) in the South. CONCLUSIONS: The presence of universal hand-held cell
phone bans were associated lower hand-held cell phone conversations across all
driver sub-groups and regions. Hand-held phone conversations were particularly
lower among female drivers and those from Western states when these bans were in
effect. Public health interventions concerning hand-held cell phone use while
driving could reasonably target all drivers.
PMID- 28499427
TI - Pars plana vitrectomy with partial tamponade of filtered air in Rhegmatogenous
retinal detachment caused by superior retinal breaks.
AB - BACKGROUND: To investigate the anatomic and functional outcomes of pars plana
vitrectomy (PPV) with partial tamponade of filtered air for rhegmatogenous
retinal detachment (RRD) caused by superior retinal breaks. METHODS:
Retrospective, comparative, consecutive case series study. Patients with RRD
caused by superior retinal breaks undergone PPV with partial tamponade (Group A)
and whole tamponade (Group B) of filtered air were included. The main outcomes
were primary and final success rates, best corrected visual acuity (BCVA), and
rate of postoperative cataract surgery. RESULTS: Forty-one patients (41 eyes)
were included in Group A and 36 patients (36 eyes) were included in Group B.
There were no significant differences in primary or final success rates between
Groups A and B (P = 0.618 and P = 1.000, respectively). The patients in Group A
experienced quicker postoperative vision improvement (from the Week 1 follow-up)
than the patients in Group B (from the Month 3 follow-up). The postoperative
cataract surgery rate of Group A (7/31) was lower than that of Group B (13/26) (P
= 0.031). CONCLUSIONS: PPV with partial tamponade of air is effective in
achieving a high anatomic success rate, quicker postoperative vision improvement,
and lower rate of postoperative cataract surgery in RRD caused by superior
retinal breaks.
PMID- 28499428
TI - Clinical benefit of adding oxaliplatin to standard neoadjuvant chemoradiotherapy
in locally advanced rectal cancer: a meta-analysis : Oxaliplatin in neoadjuvant
treatment for rectal cancer.
AB - BACKGROUND: Neoadjuvant fluoropirimidine (5FU)-based chemoradiotherapy (CRT) has
been considered the standard of care for locally advanced rectal cancer (LARC).
Whether addition of oxaliplatin (OXP) will further improve clinical outcomes is
still debated. We conducted a meta-analysis to evaluate the role of OXP in this
patient population. METHODS: Literature searches were carried out in PubMed,
Medline and Scopus databases. End points were overall survival (OS), disease free
survival (DFS), local failure (LF) and distant failure (DF). Odd ratio (OR) with
95% confidence interval (CI) was calculated using random effects model. RESULTS:
Four randomized trials were included. Patients treated with OXP-5FU CRT had
significantly decreased DF (OR = 0.76; 95% CI, 0.60 to 0.97; p = 0.03) compared
to standard CRT. OS, DFS and LF were not significantly different between groups.
CONCLUSIONS: OXP significantly decreased DF, but does not improve OS e DFS
compared to 5FU CRT. Precise role of OXP in neoadjuvant setting of LARC remains
to be determined.
PMID- 28499429
TI - Parental work absenteeism is associated with increased symptom complaints and
school absence in adolescent children.
AB - BACKGROUND: Previous studies have proposed that having parents out of work may
influence adolescent illness behaviour and school attendance. However, prior
research investigating this question has been limited by retrospective reporting
and case control studies. In a large epidemiological study we investigated
whether parental work absence was associated with symptom complaints and
increased school absenteeism in adolescents. METHODS: We analysed data from a
large epidemiological study of 10,243 Norwegian adolescents aged 16-19.
Participants completed survey at school, which included demographic data,
parental work absence and current health complaints. An official registry
provided school attendance data. RESULTS: Parental work absence was significantly
related to the number of adolescent symptom complaints as well as school
absenteeism. Having a father out of work was associated with an increased
likelihood of being in the highest quartile of symptom reporting by an odds-ratio
of 2.2 and mother by 1.6 (compared to the lowest quartile). Similarly, parental
work absenteeism was associated with an increased likelihood of being in the
highest quartile for school absence by an odds-ratio of 1.9 for a father being
out of work and 1.5 for a mother out of work. We found that the number of
adolescent symptom complaints mediated the relationship between parental work
absenteeism and school absenteeism. CONCLUSION: We found that parental work
absence was significantly associated with the number of adolescent symptom
complaints and school absenteeism. The results suggest that parents may play a
critical modelling role in the intergenerational transmission of illness and
disability behaviour.
PMID- 28499430
TI - Genome-wide DNA methylation analysis in lung fibroblasts co-cultured with silica
exposed alveolar macrophages.
AB - BACKGROUND: Exposure to crystalline silica is considered to increase the risk of
lung fibrosis. The primary effector cell, the myofibroblast, plays an important
role in the deposition of extracellular matrix (ECM). DNA methylation change is
considered to have a potential effect on myofibroblast differentiation.
Therefore, the present study was designed to investigate the genome-wide DNA
methylation profiles of lung fibroblasts co-cultured with alveolar macrophages
exposed to crystalline silica in vitro. METHODS: AM/fibroblast co-culture system
was established. CCK8 was used to assess the toxicity of AMs. mRNA and protein
expression of collagen I, alpha-SMA, MAPK9 and TGF-beta1 of fibroblasts after AMs
exposed to 100 MUg /ml SiO2 for 0-, 24-, or 48 h were determined by means of
quantitative real-time PCR, immunoblotting and immunohistochemistry. Genomic DNA
of fibroblasts was isolated using MeDIP-Seq to sequence. R software, GO, KEGG and
Cytoscape were used to analyze the data. RESULTS: SiO2 exposure increased the
expression of collagen I and alpha-SMA in fibroblasts in co-culture system.
Analysis of fibroblast methylome identified extensive methylation changes
involved in several signaling pathways, such as the MAPK signaling pathway and
metabolic pathways. Several candidates, including Tgfb1 and Mapk9, are hubs who
can connect the gene clusters. MAPK9 mRNA expression was significantly higher in
fibroblast exposed to SiO2 in co-culture system for 48 h. MAPK9 protein
expression was increased at both 24-h and 48-h treatment groups. TGF-beta1 mRNA
expression of fibroblast has a time-dependent manner, but we didn't observe the
TGF-beta1 protein expression. CONCLUSION: Tgfb1 and Mapk9 are helpful to explore
the mechanism of myofibroblast differentiation. The genome-wide DNA methylation
profiles of fibroblasts in this experimental silicosis model will be useful for
future studies on epigenetic gene regulation during myofibroblast
differentiation.
PMID- 28499431
TI - Minimal invasive percutaneous plate osteosynthesis (MIPPO) through deltoid
pectoralis approach for the treatment of elderly proximal humeral fractures.
AB - BACKGROUND: Current treatments for proximal humeral fractures include
conservative treatment, conventional open reduction internal fixation (ORIF) and
MIPPO through deltoid-splitting approach. The aim of this study was to evaluate
the clinical outcome of MIPPO versus ORIF via the deltoid-pectoralis approach in
elderly patients with proximal humeral fractures. METHODS: Thirty-six patients
with proximal humeral fractures were enrolled in this study. Following the
randomized block and single-blinded principle, the patients were assigned to two
groups and treated with either conventional ORIF or MIPPO, both through the
deltoid-pectoralis approach. Surgical outcomes were evaluated by the NEER score,
Constant-Murley score, blood loss, length of operation, radiological imaging and
clinical examination. The patients were followed up for 4-24 (mean 10) months.
RESULTS: According to Constant-Murley score, the surgical outcome was excellent
in 14 cases, satisfactory in 2 cases and unsatisfactory in one case in MIPPO
group versus 10, 5 and 4 in conventional ORIF group. MIPPO was significantly
advantageous over conventional ORIF in terms of NEER score, Constant-Murley,
length of operation and intraoperative blood loss. In addition, MIPPO was also
more advantageous in several indexes in patients with BMI > 26.0 and NEER type
III fracture. CONCLUSION: The results of our study have demonstrated that MIPPO
through the deltoid-pectoralis approach is an effective alternative for the
treatment of proximal humeral fractures in elderly patients. TRIAL REGISTRATION:
The trial registration number (TRN): ChiCTR-INR-17011098 (retrospectively
registered at 2017-04-09).
PMID- 28499432
TI - Development and evaluation of a community-based buprenorphine treatment
intervention.
AB - BACKGROUND: The majority of Americans with opioid use disorder remain out of
treatment. Operating in 33 states, Washington DC, and Puerto Rico, harm reduction
agencies, which provide sterile syringes and other health services to people who
inject drugs, are a key venue to reach out-of-treatment opioid users. Aiming to
link out-of-treatment individuals with opioid use disorder to buprenorphine
treatment, we developed a community-based buprenorphine treatment (CBBT)
intervention in collaboration with New York City harm reduction agencies.
METHODS: Intervention development included formative data collection, feasibility
testing at one harm reduction agency, and pilot testing for preliminary
effectiveness at a second harm reduction agency. We used a pre-post design for
both feasibility and pilot testing. In the CBBT intervention, we trained harm
reduction agency staff to provide (1) buprenorphine education, (2) motivational
interviewing, (3) referrals to buprenorphine-prescribing doctors, and (4)
treatment retention support. We assessed feasibility by measuring staff
satisfaction with the intervention and changes in knowledge about buprenorphine.
We assessed preliminary effectiveness by comparing rates of buprenorphine
initiation among groups of harm reduction agency clients before and after
intervention implementation. RESULTS: Among staff members at the first harm
reduction agency, knowledge increased from 52% correct answers pre-intervention
to 79% correct post-intervention. Among clients at the second harm reduction
agency, initiation of buprenorphine treatment was low and did not differ between
pre- and post-intervention groups. CONCLUSIONS: The CBBT intervention was
feasible and well-received, but initiation of buprenorphine treatment among harm
reduction agency clients was low. More robust interventions may be necessary to
increase initiation of buprenorphine treatment.
PMID- 28499433
TI - ServAR: An augmented reality tool to guide the serving of food.
AB - BACKGROUND: Accurate estimation of food portion size is a difficult task. Visual
cues are important mediators of portion size and therefore technology-based aids
may assist consumers when serving and estimating food portions. The current study
evaluated the usability and impact on estimation error of standard food servings
of a novel augmented reality food serving aid, ServAR. METHODS: Participants were
randomised into one of three groups: 1) no information/aid (control); 2) verbal
information on standard serving sizes; or 3) ServAR, an aid which overlayed
virtual food servings over a plate using a tablet computer. Participants were
asked to estimate the standard serving sizes of nine foods (broccoli, carrots,
cauliflower, green beans, kidney beans, potato, pasta, rice, and sweetcorn) using
validated food replicas. Wilcoxon signed-rank tests compared median served
weights of each food to reference standard serving size weights. Percentage error
was used to compare the estimation of serving size accuracy between the three
groups. All participants also performed a usability test using the ServAR tool to
guide the serving of one randomly selected food. RESULTS: Ninety adults (78.9%
female; a mean (95%CI) age 25.8 (24.9-26.7) years; BMI 24.2 (23.2-25.2) kg/m2)
completed the study. The median servings were significantly different to the
reference portions for five foods in the ServAR group, compared to eight foods in
the information only group and seven foods for the control group. The cumulative
proportion of total estimations per group within +/-10%, +/-25% and +/-50% of the
reference portion was greater for those using ServAR (30.7, 65.2 and 90.7%;
respectively), compared to the information only group (19.6, 47.4 and 77.4%) and
control group (10.0, 33.7 and 68.9%). Participants generally found the ServAR
tool easy to use and agreed that it showed potential to support optimal portion
size selection. However, some refinements to the ServAR tool are required to
improve the user experience. CONCLUSIONS: Use of the augmented reality tool
improved accuracy and consistency of estimating standard serve sizes compared to
the information only and control conditions. ServAR demonstrates potential as a
practical tool to guide the serving of food. Further evaluation across a broad
range of foods, portion sizes and settings is warranted.
PMID- 28499434
TI - Development of a novel immunochromatographic lateral flow assay specific for
Mycobacterium bovis cells and its application in combination with immunomagnetic
separation to test badger faeces.
AB - BACKGROUND: The European badger is an important wildlife reservoir of
Mycobacterium bovis implicated in the spread of bovine tuberculosis in the United
Kingdom and Ireland. Infected badgers are known to shed M. bovis in their urine
and faeces, which may contaminate the environment. To aid bovine tuberculosis
control efforts novel diagnostic tests for detecting infected and shedding
badgers are needed. We proposed development of a novel, rapid
immunochromatographic lateral flow device (LFD) as a non-invasive test to detect
M. bovis cells in badger faeces. Its application in combination with
immunomagnetic separation (IMS) to detect Mycobacterium bovis cells in badger
faeces is reported here. RESULTS: A novel prototype LFD for M. bovis cells was
successfully developed, with unique specificity for M. bovis and a limit of
detection 50% (LOD50%) of 1.7 * 104 M. bovis cells/ml. When IMS was employed to
selectively capture and concentrate M. bovis cells from badger faeces prior to
LFD testing, the LOD50% of the IMS-LFD assay was 2.8 * 105 M. bovis cells/ml
faecal homogenate. Faeces samples collected from latrines at badger setts in a
region of endemic bovine tuberculosis infection were tested; 78 (18%) of 441
samples tested IMS-LFD assay positive, whereas 140 (32%) tested IMS-qPCR positive
(Kappa agreement -0.009 +/- 0.044, p = 0.838). Subsequently, when 130 faeces
samples from live captured, or captive, badgers of known infection status (on the
basis of StatPak, interferon-gamma and/or culture results) were tested, the IMS
LFD assay had higher relative diagnostic specificity (Sp 0.926), but poorer
relative diagnostic sensitivity (Se 0.081), than IMS-qPCR (Sp 0.706, Se 0.581)
and IMS-culture (Sp 0.794, Se 0.436). CONCLUSIONS: The novel IMS-LFD assay,
although very specific for M. bovis, has low analytical sensitivity (indicated by
the LOD50%) and would only detect badgers shedding high numbers of M. bovis (>104
5 cells/g) in their faeces. The novel LFD would, therefore, have limited value as
a non-invasive test for badger TB surveillance purposes but it may have value for
alternative veterinary diagnostic applications.
PMID- 28499435
TI - Parasite fauna of the Antarctic dragonfish Parachaenichthys charcoti
(Perciformes: Bathydraconidae) and closely related Bathydraconidae from the
Antarctic Peninsula, Southern Ocean.
AB - BACKGROUND: As members of the Notothenioidei - the dominant fish taxon in
Antarctic waters - the family Bathydraconidae includes 12 genera and 17 species.
The knowledge of these species inhabiting an isolated environment is rather
fragmentary, including their parasite fauna. Studies on fish hosts and their
associated parasites can help gain insights into even remote ecosystems and be
used to infer ecological roles in food webs; however, ecological studies on the
Bathydraconidae are scarce. RESULTS: In this study, stomach contents and parasite
fauna of the Antarctic dragonfish species Parachaenichthys charcoti (n = 47
specimens) as well as of Gerlachea australis (n = 5), Gymnodraco acuticeps (n =
9) and Racovitzia glacialis (n = 6) were examined. The parasite fauna of P.
charcoti consisted of eight genera represented by 11 species, with three of them
being new host records. Overall, 24 parasite genera and 26 species were found in
the sampled fish, including eleven new host records. CONCLUSION: Analyses
revealed that the majority of the parasite species found in the different fish
hosts are endemic to Antarctic waters and are characterized by a broad host
range. These findings are evidence for the current lack of knowledge and the need
for further parasitological studies of fish species in this unique habitat.
PMID- 28499436
TI - Inequality in healthcare costs between residing and non-residing patients:
evidence from Vietnam.
AB - BACKGROUND: Place of residence has been shown to impact health. To date, however,
previous studies have only focused on the variability in health outcomes and
healthcare costs between urban and rural patients. This study takes a different
approach and investigates cost inequality facing non-residing patients - patients
who do not reside in the regions in which the hospitals are located.
Understanding the sources for this inequality is important, as they are directly
related to healthcare accessibility in developing countries. METHODS: The causal
impact of residency status on individual healthcare spending is documented with a
quasi-experimental design. The propensity score matching method is applied to a
unique patient-level dataset (n = 900) collected at public general and specialist
hospitals across North Vietnam. RESULTS: Propensity score matching shows that
Vietnamese patients who do not reside in the regions in which the hospitals are
located are expected to pay about 15 million Vietnamese dongs (approximately 750
USD) more than those who do, a sizable gap, given the distribution of total
healthcare costs for the overall sample. This estimate is robust to alternative
matching specifications. The obtained discrepancy is empirically attributable to
the differences in three potential contributors, namely spending on accompanying
relatives, "courtesy funds," and days of hospitalization. CONCLUSIONS: The
present study finds that there is significant inequality in healthcare spending
between residing and non-residing patients at Vietnamese hospitals and that this
discrepancy can be partially explained by both institutional and non
institutional factors. These factors signal practical channels through which
policymakers can improve healthcare accessibility.
PMID- 28499437
TI - The effect of hemostatic dressing prototypes for the uniformed services on
selected blood coagulation parameters in pigs.
AB - BACKGROUND: Serious injuries accompanied by severe bleeding are life-threatening.
Post-traumatic hemorrhage involves the risk of developing coagulopathy.
Hemostatic dressings are widely used to minimize bleeding. The application of
procoagulants in control of hemorrhage may lead to thrombosis or disseminated
intravascular coagulation. The aim of this study was to evaluate the effect of
hemostatic dressing prototypes on the porcine coagulation system. RESULTS:
Fibrinogen and D-dimer concentrations were significantly higher in the
experimental groups where hemostatic dressings were used in comparison with the
control group. Considerable differences in antithrombin III activity and thrombin
antithrombin complex concentrations were also observed between groups.
CONCLUSIONS: The hemostatic dressing comprising modified seton impregnated with
18.0 g/m2 of procoagulant was most effective in preserving the physiological
equilibrium between fibrinogenesis and fibrinolysis.
PMID- 28499438
TI - Early developed ASD (adjacent segmental disease) in patients after surgical
treatment of the spine due to cancer metastases.
AB - BACKGROUND: The causes of ASD are still relatively unknown. Correlation between
clinical status of patients and radiological MRI findings is of primary
importance. The radiological classifications proposed by Pfirmann and Oner are
most commonly used to assess intradiscal degenerative changes. The aim of the
study was to assess the influence of the extension of spine fixation on the risk
of developing ASD in a short time after surgery. METHODS: A total of 332 patients
with spinal tumors were treated in our hospital between 2010 and 2013. Of these
patients, 287 underwent surgeries. A follow-up MRI examination was performed 12
months after surgical treatment. The study population comprised of 194 patients.
Among metastases, breast cancer was predominant (29%); neurological deficits were
detected in 76 patients. Metastases were seen in the thoracic (45%) and lumbar
(30%) spine; in 25% of cases, they were of multisegmental character. Pathological
fractures concerned 88% of the patients. Statistical calculations were made using
the chi2 test. Statistical analysis was done using the Statistica v. 10 software.
A p value <0.05 was accepted as statistically significant. The study population
was divided on seven groups according to applied treatment. RESULTS: Clinical
signs of ASD were noted in only seven patients. Two patients had symptoms of
nerve root irritation in the lumbar spine. Twenty-two patients (11%) were
diagnosed with ASD according to the MRI classifications by Oner, Rijt, and Ramos,
while the more sensitive Pfirmann classification allowed to detect the disease in
46 patients (24%). Healthy or almost healthy discs of Oner type I correlated with
the criteria of Pfirmann types II and III. The percentage of the incidence of ASD
diagnosed 1 year after the surgery using the Pfirmann classifications was
significantly higher than diagnosed according to the clinical examination.
CONCLUSIONS: The incidence of ASD in patients after spine surgeries due to cancer
metastases does not differ between the study groups. ASD detectability based on
clinical signs is significantly lower than ASD detectability based on MR images
according to the system by Pfirrmann et.al. ASD risk increase among patients with
multilevel fixation.
PMID- 28499440
TI - A feasibility randomised controlled trial of extended brief intervention for
alcohol misuse in adults with mild to moderate intellectual disabilities living
in the community; The EBI-LD study.
AB - BACKGROUND: Extended brief interventions (EBIs) are effective in targeting
alcohol misuse in the general population. However, little is known of the effects
of EBI in adults with intellectual (also known as learning) disabilities. In this
feasibility trial we compared EBI with usual care for alcohol misuse in adults
with mild to moderate Intellectual Disability (ID). METHODS: The study took place
in three community ID networks of services in England. Participants aged 18-65
years with reported alcohol problems, a score >=8 on the Alcohol Use Disorder
Identification Test (AUDIT), and IQ <70 (+/5%CI) were recruited and were randomly
allocated to either EBI (five weekly sessions and one follow-up at 8 weeks) and
usual care or usual care alone. Research assistants were blind to arm allocation.
Research assessments took place at baseline, 2 and 3 months. The primary outcome
was reduction in alcohol consumption measured by the AUDIT. Preliminary health
economic analysis was performed to investigate the costs of delivering EBI and
the feasibility of a cost-effectiveness analysis in a full trial. The trial is
closed. RESULTS: Participants were recruited from January 2014 to August 2015.
Thirty individuals were randomised (15 in each arm) and provided primary outcome
data. In regard to harmful drinking, at baseline, all the participants exceeded
the relevant threshold. At 8 weeks, the proportion of participants with harmful
drinking had decreased to 60% for both groups, and at 12 weeks it had decreased
by 66 degrees 7% and 46 degrees 7% for the intervention and the control groups,
respectively. The unit cost for the delivery of EBI is L430. CONCLUSIONS:
Recruitment to this trial has been proven challenging as prevalence of alcohol
misuse in the targeted population was lower than anticipated. EBI may provide an
effective low-intensity treatment for this population. Participants' and carers'
feedback on their experience was overall positive. Further work needs to be
undertaken to ascertain the group of participants that should be participating in
a future definitive trial. TRIAL REGISTRATION: Psychological Intervention Alcohol
Misuse Learning Disability; isrctn.com, identifier: ISRCTN58783633 . Registered
on 17 December 2013.
PMID- 28499439
TI - The role of TGF-beta and its crosstalk with RAC1/RAC1b signaling in breast and
pancreas carcinoma.
AB - This article focusses on the role of TGF-beta and its signaling crosstalk with
the RHO family GTPases RAC1 and RAC1b in the progression of breast and pancreatic
carcinoma. The aggressive nature of these tumor types is mainly due to metastatic
dissemination. Metastasis is facilitated by desmoplasia, a peculiar tumor
microenvironment and the ability of the tumor cells to undergo epithelial
mesenchymal transition (EMT) and to adopt a motile and invasive phenotype. These
processes are controlled entirely or in part by TGF-beta and the small RHO GTPase
RAC1 with both proteins acting as tumor promoters in late-stage cancers. Data
from our and other studies point to signaling crosstalk between TGF-beta and RAC1
and the related isoform, RAC1b, in pancreatic and mammary carcinoma cells. Based
on the exciting observation that RAC1b functions as an endogenous inhibitor of
RAC1, we propose a model on how the relative abundance or activity of RAC1 and
RAC1b in the tumor cells may determine their responses to TGF-beta and,
ultimately, the metastatic capacity of the tumor.
PMID- 28499441
TI - Chromosomal abnormalities: subgroup analysis by maternal age and perinatal
features in zhejiang province of China, 2011-2015.
AB - BACKGROUND: Recently, the prevalence of chromosomal abnormalities (CA) increased
as the increasing proportion of mothers with advanced age. We aimed to explore
the prevalence of CA in relation to maternal age and perinatal features. METHODS:
A retrospective study was performed based on provincial birth defects
surveillance data. The relative risk (RR) and 95% confidence interval (CI) were
used to calculate maternal age-specific rates of CA. Socio-demographic
characteristics of mothers and perinatal features were listed. RESULTS: The total
prevalence of CA was 6.38 per 10,000 births, which increased per 10,000 births
linearly from 4.02 in 2011 to 9.13 in 2015 (x 2line-trend =52.69, p < 0.001).
During this period, the prevalence for CA per 10,000 births among women over 35
years old increased from 15.34 in 2011 to 33.82 in 2015 (x 2line-trend =115121.6,
p < 0.001). The RR for overall CA, trisomy 21(T21), trisomy 18(T18) and others in
mothers 35 years or older were 6.64 (95% CI 5.55 ~ 7.93), 6.83 (95% CI 5.63 ~
8.30), 4.06 (95% CI 2.09 ~ 7.90) and 7.54 (95% CI 4.02 ~ 14.11) respectively in
comparison to mothers aged 25-29 years old. The stillbirths rate for total CA was
76.45%. T21 and T18 were strongly associated with multiple anomalies, especially
congenital heart abnormalities. CONCLUSIONS: The prevalence of CA increased as
maternal age increased. Cases with CA were associated with other congenital
defects and high mortality risk.
PMID- 28499443
TI - Erratum to: DeepCpG: accurate prediction of single-cell DNA methylation states
using deep learning.
PMID- 28499442
TI - Novel glycolipid agents for killing cisplatin-resistant human epithelial ovarian
cancer cells.
AB - BACKGROUND: Chemotherapy resistance is one of the major factors contributing to
mortality from human epithelial ovarian cancer (EOC). Identifying drugs that can
effectively kill chemotherapy-resistant EOC cells would be a major advance in
reducing mortality. Glycosylated antitumour ether lipids (GAELs) are synthetic
glycolipids that are cytotoxic to a wide range of cancer cells. They appear to
induce cancer cell death in an apoptosis-independent manner. METHODS: Herein, the
effectiveness of two GAELs, GLN and MO-101, in killing chemotherapy-sensitive and
-resistant EOC cells lines and primary cell samples was tested using monolayer,
non-adherent aggregate, and non-adherent spheroid cultures. RESULTS: Our results
show that EOC cells exhibit a differential sensitivity to the GAELs. Strikingly,
both GAELs are capable of inducing EOC cell death in chemotherapy-sensitive and
resistant cells grown as monolayer or non-adherent cultures. Mechanistic studies
provide evidence that apoptotic-cell death (caspase activation) contributes to,
but is not completely responsible for, GAEL-induced cell killing in the A2780-cp
EOC cell line, but not primary EOC cell samples. CONCLUSIONS: Studies using
primary EOC cell samples supports previously published work showing a GAEL
induced caspase-independent mechanism of death. GAELs hold promise for
development as novel compounds to combat EOC mortality due to chemotherapy
resistance.
PMID- 28499445
TI - Vision-related quality of life following glaucoma filtration surgery.
AB - BACKGROUND: To evaluate vision-related quality of life (VR-QOL) following
glaucoma filtration surgery. METHODS: A total of 103 glaucoma patients scheduled
to undergo glaucoma filtration surgery. Prior to and at three months after
glaucoma filtration surgery, trabeculectomy or EX-PRESS, all patients completed
the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25). A
total of 48 patients underwent combined cataract and filtration surgery. The
clinical data collected pre- and postoperatively included best-corrected visual
acuity (BCVA) and intraocular pressure (IOP). RESULTS: The IOP decreased
significantly from 19.0 +/- 8.1 mmHg to 9.7 +/- 3.9 mmHg (P < 0.001).
Preoperative VFQ-25 composite score (65.8 +/- 15.6) was similar to the
postoperative score (67.8 +/- 16.6). A significantly improved VFQ-25 composite
score (pre: 63.2 +/- 17.1, post: 67.7 +/- 17.8; P = 0.001) was observed in the
patients who underwent combined cataract and filtration surgery. There was a
significant association between the BCVA changes in the operated eye and the
changes in the VFQ-25 composite score (r = -0.315, P = 0.003). CONCLUSIONS:
Although glaucoma filtration surgery by itself did not decrease the VR-QOL in
glaucoma patients, there was significant improvement in the VR-QOL after the
patients underwent combined cataract and glaucoma filtration surgery.
PMID- 28499444
TI - A French national breast and thyroid cancer screening programme for survivors of
childhood, adolescent and young adult (CAYA) cancers - DeNaCaPST programme.
AB - BACKGROUND: Survival of childhood, adolescent and young adult (CAYA) cancers has
increased with progress in the management of the treatments and has reached more
than 80% at 5 years. Nevertheless, these survivors are at great risk of second
cancers and non-malignant co-morbidities in later life. DeNaCaPST is a non
interventional study whose aim is to organize a national screening for thyroid
cancer and breast cancer in survivors of CAYA cancers. It will study the
compliance with international recommendations, with the aim, regarding a breast
screening programme, of offering for every woman living in France, at equal risk,
an equal screening. METHOD: DeNaCaPST trial is coordinated by the INSERM 1018
unit in cooperation with the LEA (French Childhood Cancer Survivor Study for
Leukaemia) study's coordinators, the long term follow up committee and the
paediatric radiation committee of the SFCE (French Society of Childhood Cancers).
A total of 35 centres spread across metropolitan France and la Reunion will
participate. FCCSS (French Childhood Cancer Survivor Study), LEA and central
registry will be interrogated to identify eligible patients. To participate,
centers agreed to perform a complete "long-term follow-up consultations"
according to good clinical practice and the guidelines of the SFCE (French
Society of Children Cancers). DISCUSSION: As survival has greatly improved in
childhood cancers, detection of therapy-related malignancies has become a
priority even if new radiation techniques will lead to better protection for
organs at risk. International guidelines have been put in place because of the
evidence for increased lifetime risk of breast and thyroid cancer. DeNaCaPST is
based on these international recommendations but it is important to recognize
that they are based on expert consensus opinion and are supported by neither
nonrandomized observational studies nor prospective randomized trials in this
specific population. Over-diagnosis is a phenomenon inherent in any screening
program and therefore such programs must be evaluated.
PMID- 28499447
TI - Gender difference in utilization willingness of institutional care among the
single seniors: evidence from rural Shandong, China.
AB - BACKGROUND: Institutional care has become an urgent issue in rural China. Rural
single seniors, compared with their counterparts, have lower income and are more
vulnerable. Gender is also a significant factor determining long-term
institutional care. This study is designed to examine the gender difference
towards utilization willingness of institutional care among rural single seniors.
METHODS: A total of 505 rural single seniors were included in the analysis.
Binary logistic regression model was used to examine the gender difference
towards utilization willingness for institutional care, and also to identify the
determinants of the utilization willingness for institutional care among rural
single male and female seniors. RESULTS: Our study found that about 5.7% rural
single seniors had willingness for institutional care in Shandong, China. Single
females were found to be less willing for institutional care than single males in
rural areas (OR = 0.19; 95 CI 0.06-0.57). It's also found that psychological
stress was associated with institutionalization willingness in both single males
(P = 0.045) and single females (P = 0.013) in rural China. The rural single
seniors who lived alone were found to be more willing for institutional care both
in males (P = 0.032) and females (P = 0.002) compared with those who lived with
children or others. CONCLUSIONS: This study found that there was a gender
difference towards utilization willingness for institutional care among single
seniors in rural China. Factors including psychological stress and living
arrangements were determinants of institutionalization willingness both in single
males and females. Targeted policies should be made for rural single seniors of
different gender.
PMID- 28499446
TI - Genome sequence of Shigella flexneri strain SP1, a diarrheal isolate that encodes
an extended-spectrum beta-lactamase (ESBL).
AB - BACKGROUND: Shigellosis is the most common cause of gastrointestinal infections
in developing countries. In China, the species most frequently responsible for
shigellosis is Shigella flexneri. S. flexneri remains largely unexplored from a
genomic standpoint and is still described using a vocabulary based on biochemical
and serological properties. Moreover, increasing numbers of ESBL-producing
Shigella strains have been isolated from clinical samples. Despite this, only a
few cases of ESBL-producing Shigella have been described in China. Therefore, a
better understanding of ESBL-producing Shigella from a genomic standpoint is
required. In this study, a S. flexneri type 1a isolate SP1 harboring blaCTX-M-14,
which was recovered from the patient with diarrhea, was subjected to whole genome
sequencing. RESULTS: The draft genome assembly of S. flexneri strain SP1
consisted of 4,592,345 bp with a G+C content of 50.46%. RAST analysis revealed
the genome contained 4798 coding sequences (CDSs) and 100 RNA-encoding genes. We
detected one incomplete prophage and six candidate CRISPR loci in the genome. In
vitro antimicrobial susceptibility testing demonstrated that strain SP1 is
resistant to ampicillin, amoxicillin/clavulanic acid, cefazolin, ceftriaxone and
trimethoprim. In silico analysis detected genes mediating resistance to
aminoglycosides, beta-lactams, phenicol, tetracycline, sulphonamides, and
trimethoprim. The bla CTX-M-14 gene was located on an IncFII2 plasmid. A series
of virulence factors were identified in the genome. CONCLUSIONS: In this study,
we report the whole genome sequence of a blaCTX-M-14-encoding S. flexneri strain
SP1. Dozens of resistance determinants were detected in the genome and may be
responsible for the multidrug-resistance of this strain, although further
confirmation studies are warranted. Numerous virulence factors identified in the
strain suggest that isolate SP1 is potential pathogenic. The availability of the
genome sequence and comparative analysis with other S. flexneri strains provides
the basis to further address the evolution of drug resistance mechanisms and
pathogenicity in S. flexneri.
PMID- 28499448
TI - Comparison of demographic characteristics and psychiatric comorbidity among
methamphetamine-, heroin- and methamphetamine-heroin co- dependent males in
Hunan, China.
AB - BACKGROUND: There is little research of psychiatric comorbidity differences among
people with different types of drug dependence in Chinese population. We explored
demographic and comorbid psychiatric differences among methamphetamine- dependent
males (MDs), heroin-dependent males (HDs) and methamphetamine and heroin co
dependent males (M/HDs) in Hunan province, China. METHODS: A cross-sectional,
structured and clinical interview method was used to examine differences in DSM
IV-TR Axis I Disorders among 346 MDs, 698 HDs and 247 M/HDs from three compulsory
rehabilitation centers and two voluntary rehabilitation centers in Hunan.
RESULTS: MDs and M/HDs were younger, more likely to choose inhalation
administration, less likely to have a family history of substance use, less
likely to have undergone detoxification treatment, had higher incomes and shorter
duration of drug use than HDs. Overall, methamphetamine-dependence related to
higher rates of current and lifetime psychotic disorders, lifetime hallucinogen
use disorders. Heroin-dependence related to higher rates of current and lifetime
substance-induced mood disorders, sedative/hypnotic/anxiolytic and other drug use
disorders and current alcohol use disorder. For M/HDs, they were more likely to
have any other lifetime substance use disorders than MDs and HDs. CONCLUSIONS:
There were substantial differences in epidemiological characteristics and
comorbidity among MD, HD and M/HD groups, which highlights the urgent need to
develop treatment services and policies for drug-specific users in China.
PMID- 28499449
TI - PERK induces resistance to cell death elicited by endoplasmic reticulum stress
and chemotherapy.
AB - BACKGROUND: Nutrient deprivation, hypoxia, radiotherapy and chemotherapy induce
endoplasmic reticulum (ER) stress, which activates the so-called unfolded protein
response (UPR). Extensive and acute ER stress directs the UPR towards activation
of death-triggering pathways. Cancer cells are selected to resist mild and
prolonged ER stress by activating pro-survival UPR. We recently found that drug
resistant tumor cells are simultaneously resistant to ER stress-triggered cell
death. It is not known if cancer cells adapted to ER stressing conditions acquire
a chemoresistant phenotype. METHODS: To investigate this issue, we generated
human cancer cells clones with acquired resistance to ER stress from ER stress
sensitive and chemosensitive cells. RESULTS: ER stress-resistant cells were cross
resistant to multiple chemotherapeutic drugs: such multidrug resistance (MDR) was
due to the overexpression of the plasma-membrane transporter MDR related protein
1 (MRP1). Gene profiling analysis unveiled that cells with acquired resistance to
ER stress and chemotherapy share higher expression of the UPR sensor protein
kinase RNA-like endoplasmic reticulum kinase (PERK), which mediated the erythroid
derived 2-like 2 (Nrf2)-driven transcription of MRP1. Disrupting PERK/Nrf2 axis
reversed at the same time resistance to ER stress and chemotherapy. The inducible
silencing of PERK reduced tumor growth and restored chemosensitivity in resistant
tumor xenografts. CONCLUSIONS: Our work demonstrates for the first time that the
adaptation to ER stress in cancer cells produces a MDR phenotype. The
PERK/Nrf2/MRP1 axis is responsible for the resistance to ER stress and
chemotherapy, and may represent a good therapeutic target in aggressive and
resistant tumors.
PMID- 28499450
TI - Intrabodies against the Polysialyltransferases ST8SiaII and ST8SiaIV inhibit
Polysialylation of NCAM in rhabdomyosarcoma tumor cells.
AB - BACKGROUND: Polysialic acid (polySia) is a carbohydrate modification of the
neural cell adhesion molecule (NCAM), which is implicated in neural
differentiation and plays an important role in tumor development and metastasis.
Polysialylation of NCAM is mediated by two Golgi-resident polysialyltransferases
(polyST) ST8SiaII and ST8SiaIV. Intracellular antibodies (intrabodies; IB)
expressed inside the ER and retaining proteins passing the ER such as cell
surface receptors or secretory proteins provide an efficient means of protein
knockdown. To inhibit the function of ST8SiaII and ST8SiaIV specific ER IBs were
generated starting from two corresponding hybridoma clones. Both IBs
alphaST8SiaII-IB and alphaST8SiaIV-IB were constructed in the scFv format and
their functions characterized in vitro and in vivo. RESULTS: IBs directed against
the polySTs prevented the translocation of the enzymes from the ER to the Golgi
apparatus. Co-immunoprecipitation of ST8SiaII and ST8SiaIV with the corresponding
IBs confirmed the intracellular interaction with their cognate antigens. In CHO
cells overexpressing ST8SiaII and ST8SiaIV, respectively, the transfection with
alphaST8SiaII-IB or alphaST8SiaIV-IB inhibited significantly the cell surface
expression of polysialylated NCAM. Furthermore stable expression of ST8SiaII-IB,
ST8SiaIV-IB and luciferase in the rhabdomyosarcoma cell line TE671 reduced cell
surface expression of polySia and delayed tumor growth if cells were xenografted
into C57BL/6 J RAG-2 mice. CONCLUSION: Data obtained strongly indicate that
alphaST8SiaII-IB and alphaST8SiaIV-IB are promising experimental tools to analyze
the individual role of the two enzymes during brain development and during
migration and proliferation of tumor cells.
PMID- 28499451
TI - Effects of annulus defects and implantation of poly(lactic-co-glycolic acid)
(PLGA)/fibrin gel scaffolds on nerves ingrowth in a rabbit model of annular
injury disc degeneration.
AB - BACKGROUND: Growth of nerve fibers has been shown to occur in a rabbit model of
intravertebral disc degeneration (IVD) induced by needle puncture. As nerve
growth may underlie the process of chronic pain in humans affected by disc
degeneration, we sought to investigate the factors underlying nerve ingrowth in a
minimally invasive annulotomy rabbit model of IVD by comparing the effects of
empty disc defects with those of defects filled with poly(lactic-co-glycolic
acid)/fibrin gel (PLGA) plugs. METHODS: New Zealand white rabbits (n = 24)
received annular injuries at three lumbar levels (L3/4, L4/5, and L5/6). The
discs were randomly assigned to four groups: (a) annular defect (1.8-mm diameter;
4-mm depth) by mini-trephine, (b) annular defect implanted with a PLGA scaffold
containing a fibrin gel, (c) annular puncture by a 16G needle (5-mm depth), and
(d) uninjured L2/3 disc (control). Disc degeneration was evaluated by
radiography, MRI, histology, real-time PCR, and analysis of proteoglycan (PG)
content. Nerve ingrowth into the discs was assessed by immunostaining with the
nerve marker protein gene product 9.5. RESULTS: Injured discs showed a
progressive disc space narrowing with significant disc degeneration and
proteoglycan loss, as confirmed by imaging results, molecular and compositional
analysis, and histological examinations. In 16G punctured discs, nerve ingrowth
was observed on the surface of scar tissue. In annular defects, nerve fibers were
found to be distributed along small fissures within the fibrocartilaginous-like
tissue that filled the AF. In discs filled with PLGA/ fibrin gel, more nerve
fibers were observed growing deeper into the inner AF along the open annular
track. In addition, innervations scores showed significantly higher than those
of punctured discs and empty defects. A limited vascular proliferation was found
in the injured sites and regenerated tissues. CONCLUSIONS: Nerve ingrowth was
significantly higher in PLGA/fibrin-filled discs than in empty defects. Possible
explanations include (i) annular fissures along the defect and early loss of
proteoglycan may facilitate the ingrowth process and (ii) biodegradable
PLGA/fibrin gel may promote adverse growth of nerves and blood vessels into
deeper parts of injured disc. The rabbit annular defect model of disc
degeneration appears suitable to investigate the effects of nerve ingrowth in
relation to pain generation.
PMID- 28499453
TI - Monitoring urban beaches with qPCR vs. culture measures of fecal indicator
bacteria: Implications for public notification.
AB - BACKGROUND: The United States Environmental Protection Agency has established
methods for testing beach water using the rapid quantitative polymerase chain
reaction (qPCR) method, as well as "beach action values" so that the results of
such testing can be used to make same-day beach management decisions. Despite its
numerous advantages over culture-based monitoring approaches, qPCR monitoring has
yet to become widely used in the US or elsewhere. Considering qPCR results
obtained on a given day as the best available measure of that day's water
quality, we evaluated the frequency of correct vs. incorrect beach management
decisions that are driven by culture testing. METHODS: Beaches in Chicago, USA,
were monitored using E. coli culture and enterococci qPCR methods over 894 beach
days in the summers of 2015 and 2016. Agreement in beach management using the two
methods, after taking into account agreement due to chance, was summarized using
Cohen's kappa statistic. RESULTS: No meaningful agreement (beyond that expected
by chance) was observed between beach management actions driven by the two pieces
of information available to beach managers on a given day: enterococci qPCR
results ofsamples collected that morning and E. coli culture results of samples
collected the previous day. The E. coli culture beach action value was exceeded
3.4 times more frequently than the enterococci qPCR beach action value (22.6 vs.
6.6% of beach-days). CONCLUSIONS: The largest evaluation of qPCR-based beach
monitoring to date provides little scientific rationale for continued E. coli
culture testing of beach water in our setting. The observation that the E. coli
culture beach action value was exceeded three times as frequently as the
enterococci qPCR beach action value suggests that, although the beach action
values for bacteria using different measurement methods are thought to provide
comparable information about health risk, this does not appear to be the case in
all settings.
PMID- 28499454
TI - Risk for intracranial pressure increase related to enclosed air in post
craniotomy patients during air ambulance transport: a retrospective cohort study
with simulation.
AB - BACKGROUND: Post-craniotomy intracranial air can be present in patients scheduled
for air ambulance transport to their home hospital. We aimed to assess risk for
in-flight intracranial pressure (ICP) increases related to observed intracranial
air volumes, hypothetical sea level pre-transport ICP, and different potential
flight levels and cabin pressures. METHODS: A cohort of consecutive subdural
hematoma evacuation patients from one University Medical Centre was assessed with
post-operative intracranial air volume measurements by computed tomography.
Intracranial pressure changes related to estimated intracranial air volume
effects of changing atmospheric pressure (simulating flight and cabin pressure
changes up to 8000 ft) were simulated using an established model for intracranial
pressure and volume relations. RESULTS: Approximately one third of the cohort had
post-operative intracranial air. Of these, approximately one third had
intracranial air volumes less than 11 ml. The simulation estimated that the
expected changes in intracranial pressure during 'flight' would not result in
intracranial hypertension. For intracranial air volumes above 11 ml, the
simulation suggested that it was possible that intracranial hypertension could
develop 'inflight' related to cabin pressure drop. Depending on the pre-flight
intracranial pressure and air volume, this could occur quite early during the
assent phase in the flight profile. DISCUSSION: These findings support the idea
that there should be radiographic verification of the presence or absence of
intracranial air after craniotomy for patients planned for long distance air
transport. CONCLUSIONS: Very small amounts of air are clinically inconsequential.
Otherwise, air transport with maintained ground-level cabin pressure should be a
priority for these patients.
PMID- 28499452
TI - Current status and perspectives of patient-derived xenograft models in cancer
research.
AB - Cancers remain a major public health problem worldwide, which still require
profound research in both the basic and preclinical fields. Patient-derived
xenograft (PDX) models are created when cancerous cells or tissues from patients'
primary tumors are implanted into immunodeficient mice to simulate human tumor
biology in vivo, which have been extensively used in cancer research. The routes
of implantation appeared to affect the outcome of PDX research, and there has
been increasing applications of patient-derived orthotopic xenograft (PDOX)
models. In this review, we firstly summarize the methodology to establish PDX
models and then go over recent application and function of PDX models in basic
cancer research on the areas of cancer characterization, initiation,
proliferation, metastasis, and tumor microenvironment and in preclinical
explorations of anti-cancer targets, drugs, and therapeutic strategies and
finally give our perspectives on the future prospects of PDX models.
PMID- 28499455
TI - Bovis Bacillus Calmette-Guerin (BCG) infection induces exosomal miRNA release by
human macrophages.
AB - BACKGROUND: Tuberculosis (TB) remains a significant global health concern and its
diagnosis is challenging due to the limitations in the specificity and
sensitivity of the current diagnostic tests. Exosomes are bioactive 30-100 nm
vesicles produced by most cell types and are found in almost all human body
fluids. Exosomal microRNAs (miRNAs) can transfer biological information between
cells and tissues and may act as potential biomarkers in many diseases. In this
pilot study, we assessed the miRNA profile of exosomes released from human
monocyte-derived macrophages upon infection with Mycobacterium bovis Bacillus
Calmette-Guerin (BCG). METHODS: Human monocytes were obtained from the peripheral
blood of three healthy subjects and driven to a monocyte-derived macrophage (MDM)
phenotype using standard protocols. MDMs were infected with BCG or left
uninfected as control. 72 h post-infection, exosomes were collected from the cell
culture medium, RNA was isolated and RNA-seq performed. The raw reads were
filtered to eliminate adaptor and primer sequences and the sequences were run
against the mature human miRNA sequences available in miRBase. MicroRNAs were
identified using an E value <0.01. miRNA network analysis was performed using the
DIANA miRNA tool, miRDB and functional KEGG pathway analysis. RESULTS: Infection
of MDMs with BCG leads to the release of several exosomal miRNAs. These included
miR-1224, -1293, -425, -4467, -4732, -484, -5094, -6848-6849, -4488 and -96 all
of which were predicted to target metabolism and energy production-related
pathways. CONCLUSIONS: This study provides evidence for the release of specific
exosomal miRNAs from BCG-infected MDMs. These exosomal miRNAs reflect host
pathogen interaction and subversion of host metabolic processes following
infection.
PMID- 28499456
TI - Role of microRNAs in premature ovarian insufficiency.
AB - Premature ovarian insufficiency (POI) is a typical disorder of amenorrhea lasting
for a minimum of 4 months. The typical characteristics comprised of declined
estrogen and raised serum concentrations of follicle-stimulating hormone (FSH) in
women <40-year-old, primarily originating from iatrogenic factors, karyotypic
abnormalities, and genetic factors. However, the etiology of POI remains unknown
in approximately 90% of cases. POI could lead to infertility, osteoporosis,
cardiovascular disorder, and cognitive dysfunction. MicroRNAs (miRNAs) are a
class of endogenous noncoding RNAs (ncRNAs) that can mediate post-translational
silencing of the genes involved in the regulation of proliferation,
differentiation, apoptosis, development, tumorigenesis, and hematopoiesis.
Recently, the regulatory functions of miRNAs in the development of POI have been
the topic of intensive research. The present review addresses the association of
miRNAs' machinery genes (Dicer, Drosha, and XPO5) with POI and the miRNA
expression profiles in the plasma of patients with POI. In addition, several
specific miRNAs (miR-23a, miR-27a, miR-22-3p, miR-146a, miR-196a, miR-290-295,
miR-423, and miR-608) related to POI are also examined in order to highlight the
issues that deserve further investigation. A thorough understanding of the exact
regulatory roles of miRNAs is imperative to gain novel insights into the etiology
of idiopathic POI and offer new research directions in the field.
PMID- 28499458
TI - Evaluation of a Multilocus Sequence Typing (MLST) scheme for Leishmania (Viannia)
braziliensis and Leishmania (Viannia) panamensis in Colombia.
AB - BACKGROUND: Leishmaniases are parasitic vector-borne diseases affecting more than
12 million people in 98 countries. In Colombia, leishmaniasis is widespread and
the most common clinical manifestation is cutaneous, mainly caused by L.
panamensis and L. braziliensis. Currently, the genetic diversity of these species
in Colombia is unknown. To address this, we applied molecular techniques for
their characterization, using multilocus sequence typing (MLST) to explore the
genetic variability and phylodynamics of the disease. METHODS: Seven previously
described genetic markers were selected highlighting the implementation of a
mitochondrial marker. Markers were applied to 163 samples from isolates obtained
between 1980 and 2001. RESULTS: The identification of the samples showed an
excellent correlation with typing tests previously applied (MLEE, monoclonal
antibodies). Isolates of L. braziliensis showed greater genetic diversity than L.
panamensis, and a greater number of diploid sequence types (DSTs). In addition,
the geographical distribution of DSTs for each species were obtained through
georeferencing maps. CONCLUSIONS: To our knowldge, this study represents the
first description of the genetic variability of L. panamensis in Colombia and
South America, and is the first to propose a scheme of MLST for epidemiological
surveillance of leishmaniasis in the country.
PMID- 28499457
TI - Preconditioning of bone marrow-derived mesenchymal stromal cells by
tetramethylpyrazine enhances cell migration and improves functional recovery
after focal cerebral ischemia in rats.
AB - BACKGROUND: Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs)
is one of the new therapeutic strategies for treating ischemic stroke. However,
the relatively poor migratory capacity of BMSCs toward infarcted regions limited
the therapeutic potential of this approach. Pharmacological preconditioning can
increase the expression of CXC chemokine receptor 4 (CXCR4) in BMSCs and enhance
cell migration toward the injury site. In the present study, we investigated
whether tetramethylpyrazine (TMP) preconditioning could enhance BMSCs migration
to the ischemic brain and improve functional recovery through upregulating CXCR4
expression. METHODS: BMSCs were identified by flow cytometry analysis. BMSCs
migration was evaluated in vitro by transwell migration assay, and CXCR4
expression was measured by quantitative reverse transcription-polymerase chain
reaction and western blot analysis. In rats with focal cerebral ischemia, the
neurological function was evaluated by the modified neurological severity score,
the adhesive removal test and the corner test. The homing BMSCs and angiogenesis
were detected by immunofluorescence, and expression of stromal cell-derived
factor-1 (SDF-1) and CXCR4 was measured by western blot analysis. RESULTS: Flow
cytometry analysis demonstrated that BMSCs expressed CD29 and CD90, but not CD34
and CD45. TMP pretreatment dose-dependently induced BMSCs migration and CXCR4
expression in vitro, which was significantly inhibited by AMD3100, a CXCR4
antagonist. In rat stroke models, we found more TMP-preconditioned BMSCs homing
toward the infarcted regions than nonpreconditioned cells, leading to improved
neurological performance and enhanced angiogenesis. Moreover, TMP-preconditioned
BMSCs significantly upregulated the protein expression of SDF-1 and CXCR4 in the
ischemic boundary regions. These beneficial effects of TMP preconditioning were
blocked by AMD3100. CONCLUSION: TMP preconditioning enhances the migration and
homing ability of BMSCs, increases CXCR4 expression, promotes angiogenesis, and
improves neurological performance. Therefore, TMP preconditioning may be an
effective strategy to improve the therapeutic potency of BMSCs for ischemic
stroke due to enhanced BMSCs migration to ischemic regions.
PMID- 28499460
TI - The Euromelanoma Campaign.
PMID- 28499459
TI - Dispatch and prehospital transport for acute septic patients: an observational
study.
AB - BACKGROUND: In order to dispatch ambulances with the correct level of urgency,
the dispatch center has to balance the perceived urgency and traffic safety
considerations with the available resources. As urgency is not clear in all
clinical situations, some high urgency patients may end up with a suboptimal mode
of transport. Patients with severe sepsis or septic shock suffer from highly time
dependent conditions but they present with a wide range of symptoms, which might
be difficult to identify in the dispatch system. The aim of the study is to
investigate the modes of prehospital transport among acute admitted patients with
sepsis, severe sepsis and septic shock. METHODS: We included all adult patients
(>=15 years) presenting to an acute medical unit at Odense University Hospital
with a first-time admission of community-acquired sepsis between September 2010
August 2011. Cases and prehospital ambulance transport were identified by
structured manual chart review. In all cases it was registered, whether the
ordinary ambulance was assisted by the mobile emergency care unit (MECU), manned
by anesthesiologists. RESULTS: We included 1,713 patients median age 72 years
(IQR 57-81), 793 (46.3%) male, 621 (36.3%) had sepsis, 1,071 (62.5%) severe
sepsis, and 21 (1.2%) septic shock. In the group of sepsis patients, 390 (62.8%)
arrived without public prehospital transport, 197 (31.7%) were transported by
ambulance, and 34 (5.5%) were assisted by MECU. In the group of severe sepsis
patients, the same percentage 62.8% arrived without public pre-hospital
transport, a lower percentage 28.2% were transported by ambulance, and a larger
percentage 9.0% were transported by MECU. Among 21 patients with septic shock, 10
arrived without public pre-hospital transport (47.7%), 7 (33.3%) were transported
by ambulance, and 4 (19.0%) by MECU. The 30-day mortality hazard ratio was
associated with mode of transport, with the adjusted highest hazard ratio found
in the group of MECU transported patients 1.76 (95%Cl 1.16-2.66). CONCLUSIONS: A
substantial proportion of patients with severe sepsis and septic shock arrive to
hospital without public prehospital transport or by unspecialized ambulances.
PMID- 28499461
TI - Nitric oxide: A possible new biomarker in heart failure? Relationship with
pulmonary hypertension secondary to left heart failure.
PMID- 28499462
TI - A stressful work environment is associated with tinnitus: Initial evidence from
Asia.
PMID- 28499463
TI - Diffusion control for a tempered anomalous diffusion system using fractional
order PI controllers.
AB - This paper is concerned with diffusion control problem of a tempered anomalous
diffusion system based on fractional-order PI controllers. The contribution of
this paper is to introduce fractional-order PI controllers into the tempered
anomalous diffusion system for mobile actuators motion and spraying control. For
the proposed control force, convergence analysis of the system described by
mobile actuator dynamical equations is presented based on Lyapunov stability
arguments. Moreover, a new Centroidal Voronoi Tessellation (CVT) algorithm based
on fractional-order PI controllers, henceforth called FOPI-based CVT algorithm,
is provided together with a modified simulation platform called Fractional-Order
Diffusion Mobile Actuator-Sensor 2-Dimension Fractional-Order Proportional
Integral (FO-Diff-MAS2D-FOPI). Finally, extensive numerical simulations for the
tempered anomalous diffusion process are presented to verify the effectiveness of
our proposed fractional-order PI controllers.
PMID- 28499464
TI - Prospective study on ocular motility limitation due to orbital muscle entrapment
or impingement associated with orbital wall fracture.
AB - INTRODUCTION: The recommended urgent surgical management of ocular motility
restriction due to orbital muscle entrapment or impingement associated with
orbital wall fracture needs to be elucidated. AIM: To evaluate the importance of
the time from injury to surgery for the outcome in ocular motility and diplopia,
the time lapse of ocular motility, diplopia and hypesthesia recovery. MATERIAL
AND METHODS: Patients with entrapment or impingement of orbital contents due to
orbital wall fracture were followed up prospectively over 1year regarding ocular
motility, diplopia, hypesthesia and cosmetic deformity. RESULTS: 21 patients (10
entrapments and 11 impingements) were included and treated surgically. The median
time from injury to surgery was 36 (8-413)h for the entrapment group and 168 (48
326)h for the impingement group. The median time from study inclusion to surgery
was 0 (0-1) days for the entrapment group and 1.0 (0.2-4.8) days for the
impingement group. All the patients had ocular motility limitation and diplopia
at the inclusion. Ocular motility improved gradually and was normal at final
visit. Diplopia resolved gradually in all patients except in two with non
disturbing diplopia, at the final visit. Forced duction test was positive in 90%
of the patients in the entrapment group and 70% in impingement group. At final
visit, hypesthesia was found in none of the patients in the entrapment group but
in 4 patients in the impingement group. CONCLUSIONS: In this, the first
prospective long term follow up of orbital wall fractures with ocular motility
restriction, we did not find any significant correlation between the time from
injury to surgery and the outcomes in ocular motility and diplopia. An entrapment
requires surgery as soon as possible; however, the surgical reduction is at least
as important as surgical timing. Surgery should be delayed until it can be
performed by an experienced surgeon. Ocular motility restriction causing diplopia
due to impingement is not an ophthalmologic emergency and surgery is recommended
if the diplopia and ocular motility has not improved over time. Clinical
examination of ocular motility and not CT scan findings is crucial to determine
whether a limitation of ocular motility exists or not.
PMID- 28499465
TI - Current treatment of infected non-union after intramedullary nailing.
AB - Non-union is a devastating consequence of a fracture. Non-unions cause
substantial patient morbidity with patients suffering from loss of function of
the affected extremity, increased pain, and a substantial decrease in the quality
of life. The management is often associated with repeated, unsuccessful
operations resulting in prolonged hospital stays, which has social and economic
consequences to both the patient and the healthcare system. The rates of non
union following intramedullary (IM) nailing vary according to anatomical
location. There is currently no consensus regarding the treatment of infected non
unions following IM nailing, but the most common procedures reported are;
exchange IM nail with antibiotic suppression or excision of the non-union,
(stabilisation with external fixation or less commonly plate or IM nail) and then
reconstruction of the bone defect with distraction osteogenesis or the Masquelet
technique. This article explores the general principles of treatment, fixation
modalities and proposes a treatment strategy for the management of infected non
unions following intramedullary nailing.
PMID- 28499466
TI - Technical considerations to avoid delayed and non-union.
AB - For many years intramedullary nails have been a well accepted and successful
method of diaphyseal fracture fixation. However, delayed and non unions with this
technique do still occur and are associated with significant patient morbidity.
The reason for this can be multi-factorial. We discuss a number of technical
considerations to maximise fracture reduction, fracture stability and fracture
vascularity in order to achieve bony union.
PMID- 28499468
TI - Corrigendum to "Ultrasensitive and selective electrochemical biosensor for
detection of mercury (II) ions by nicking endonuclease-assisted target recycling
and hybridization chain reaction signal amplification" [Biosens. Bioelectron. 94
(2017) 19-23].
PMID- 28499467
TI - Secondary sinus lift: a viable option to increase contact of bone to implant.
PMID- 28499469
TI - Phylogenetically diverse groups of Bradyrhizobium isolated from nodules of tree
and annual legume species growing in Ethiopia.
AB - Bacteria belonging to the genus Bradyrhizobium nodulate various leguminous woody
plants and herbs, including economically important crops such as soybean, peanut
and cowpea. Here we analysed 39 Bradyrhizobium strains originating from root
nodules of the leguminous trees and crops Acacia saligna, Faidherbia albida,
Erythrina brucei, Albizia gummifera, Millettia ferruginea, Cajanus cajan, Vigna
unguiculata and Phaseolus vulgaris, growing in southern Ethiopia. Multilocus
sequence analyses (MLSA) of the 16S rRNA, glnII, recA, gyrB and dnaK genes and
the ITS region grouped the test strains into seven well-supported genospecies (I
VII), six of which occupied distinct positions excluding all hitherto defined
Bradyrhizobium species. Analyses of the nodA, nodC and nifH genes suggested
different evolutionary history of the chromosomal and symbiosis-related genes.
Our study corroborates earlier findings that Ethiopia is a hotspot for rhizobial
biodiversity, justifying further search for novel strains from this region and
calling for intensified research on the ecology and biochemistry of these
organisms.
PMID- 28499470
TI - Exercise and environment: New qualitative work to link popular practice and
public health.
AB - The health benefits of physical activity are many and well known. Those hoping to
promote public health are therefore understandably keen on encouraging physical
exercise. This commentary considers the role of qualitative research in this
undertaking, given a context in which medical researchers have more commonly
taken a quantitative approach to the motivations that are thought to underpin
exercise. Our core argument is that studies concerned with how particular
environments are inhabited by particular groups of exercisers could play a more
central part in public health promotion. In making this case, and by way of an
introduction to this Health and Place special issue, we present a series of
statements that we think could usefully guide the further development of this
work. Specifically, we argue for further attention to: the ways in which
different material settings play into the exercise experience; how many of the
exercise practices that we may hope to understand sit rather uneasily with the
idea of sport; the subtleties of how sociality features in contemporary exercise
practices; the physical pleasures that come from exercise; and how exercise
practices are both acquired by individuals and evolve as a whole. In so doing,
the aim is to encourage relevant researchers to engage more directly in
conversation with health promoters instead of either being indifferent to, or
critical of, them.
PMID- 28499472
TI - ?
PMID- 28499471
TI - Cytoskeletal connectivity may guide erythrocyte membrane ex- and invagination - A
discussion point how biophysical principles might be exploited by a parasite
invading erythrocytes.
PMID- 28499473
TI - [Child protection, a question of society].
AB - Child protection is a sector undergoing major changes in which local authorities
play a central role. There are several different types of child protection
measures covering different needs: monitoring in the home, foster family,
placement in a children's home or a stay in a mother-and-baby centre for young
mothers. For all these children and adolescents, leaving care is a key moment
which requires support.
PMID- 28499474
TI - [Legislative evolution and regulatory framework of child placement].
AB - In the area of child protection, French law has evolved considerably over recent
decades. Leal texts provide the system with a very precise structure, in order to
organise child protection on an administrative and judicial level.
PMID- 28499475
TI - [Clinical application of attachment].
AB - By favouring the proximity of a caregiver, attachment is essential for enabling
children to live and grow. It constitutes both an emotion regulator and an
internal security base. It is a complex process which evolves throughout a
person's lifetime.
PMID- 28499476
TI - ["Operation pouponnieres", yesterday and today: placement or a living
environment?]
AB - For several decades, major progress has been made in changing and improving
living conditions for children placed in an infant care home. From hospitalism to
the emergence of the concept of compassionate care, professionals have constantly
striven to support this evolution.
PMID- 28499477
TI - [Placement, a therapeutic act].
AB - Any proposed placement of a child is carried out with the aim of providing
protection as well as care. The therapeutic aspect is not straightforward, as it
comes up against the repetition of situations, the anxiety and the defences of
all concerned. In these complex situations, it is essential to provide suitable
care to the child and their parents.
PMID- 28499478
TI - [The nurse and child health nurse at the heart of the care in an infant care
home].
AB - Infant care homes cater for children up to the age of 3. The work of the nurse
and the child health nurse lies at the heart of the care project, helping the
children to construct themselves and develop. The harmonisation of practices and
continuity are essential notions.
PMID- 28499480
TI - [The place of the parents in an infant care home].
AB - In the infant unit of Chambery children's home, the organisation of parental
visits is the fruit of an institutional project. Practices have changed over the
years. The reflection and the responsiveness of the professionals and their
desire to create a secure environment for the children and the parents, have
enabled them to establish a setting which favours the preservation of the parent
child bond.
PMID- 28499479
TI - [Different perspectives on caring for a child in an infant care home].
AB - Caring for a child in an infant care home leads professionals to examine their
practices. Perrine Hugel, manager of an infant care home, and Maud Leon, an
auxiliary child health nurse in the same home, describes the nursing values which
they implement on a daily basis to favour the wellbeing of the infant and support
parenthood.
PMID- 28499481
TI - [Supporting the parental function in the case of child placement].
AB - When a child is placed in care, it is important that the parents' access visit
can take place in an environment which helps to support the parental function.
Time remains a major component which professionals must understand in order to
support the children and their parents along this long pathway. This article
presents the experience of the Diapason service, a meeting place for parents of
children in care.
PMID- 28499482
TI - [A scheme to support teenagers in care].
AB - In some family situations, the placement of a teenager, even in the case of a
court decision, proves ineffective. The accumulation of all kinds of difficulties
requires a different type of support, based on responsiveness, attention and
above all time to come together. A dedicated scheme helps to prevent situations
of waywardness or marginalisation among these teenagers and to support the
families.
PMID- 28499483
TI - ["An adopted family for Katherina"].
AB - A foster mother took into her home Katherina, a 5-month-old girl placed by the
child welfare services. Before taking the decision, she discussed it with her
partner and her own children. Straight after Katherina's arrival, visits were
organised in order to maintain, as much as possible, the child's bond with her
mother.
PMID- 28499484
TI - [Adverse events in neonatology, contribution of a standardised register].
AB - Despite the recommendation to report all adverse events to the risk management
unit, such reporting is far from consistent. An internal, standardised register
of adverse events, was put in place in a neonatology unit for six months. An
analysis of the reports has led to the reorganisation of the unit and practices
as part of a drive to improve the quality of care.
PMID- 28499485
TI - ?
PMID- 28499486
TI - Intra-osseous local anaesthetic patellar pain catheter suppresses osteoarthritic
patello-femoral pain.
AB - BACKGROUND: The source of pain in patellofemoral osteoarthritis is not fully
understood. The purpose of this study was to identify the origin of pain using
intraosseous pain catheters and to show early results with an osteotomy that is
potentially denervating and hydrostatic pressure-relieving. METHODS: Five
patients with patellofemoral osteoarthritis and pain with straight downward
patellofemoral compression were included. All underwent arthroscopic placement of
two 0.8mm catheters into the medial and lateral patella prior to subsequent
patellar facetectomy with an incomplete horizontal patellar osteotomy. The
catheters were first flushed with 0.5ml saline, then with local anaesthetic to
determine pain response. After a mean of 44months the latest clinical examination
was performed. RESULTS: Instillation of less than 0.5ml of saline provoked sharp
pain, which could be localised by all patients as medial or lateral within the
patella. Subsequent instillation of local anaesthetic suppressed the mean
patellar tenderness during axial compression from VAS 6 to VAS 1. In one of the
five patients, patellar osteotomy did not relieve symptoms and further surgical
intervention was required. The remaining four patients experienced a clinical
improvement with a mean subjective knee value of 55 (range 40 to 65) out of 100.
CONCLUSION: This is the first report on intraosseous catheters applying local
anaesthetics into bone. There is a surprisingly precise intraosseous spatial
resolution of pain perception in the patella and triggering of pain in
osteoarthritis appears at least in part to occur through intraosseous increase of
hydrostatic pressure. LEVEL OF EVIDENCE: Level IV, Case Series.
PMID- 28499487
TI - External beam radiation therapy with or without low-dose-rate brachytherapy:
Analysis of favorable and unfavorable intermediate-risk prostate cancer patients.
AB - PURPOSE: To compare the tumor control and toxicity in men with intermediate-risk
prostate cancer treated with either external beam radiation therapy (EBRT) or
EBRT plus low-dose-rate brachytherapy (combo-RT). METHODS AND MATERIALS: Between
1995 and 2012, 579 men with intermediate-risk prostate cancer were treated with
either EBRT (n = 388) or combo-RT (n = 191). Outcomes assessed included
biochemical recurrence-free survival (bRFS), distant metastasis-free survival
(DMFS), and cumulative incidence of genitourinary (GU) and gastrointestinal
toxicity. Favorable and unfavorable intermediate-risk subgroups were analyzed.
RESULTS: Median followup was 7.5 years. Combo-RT group had improved 10-year bRFS
compared with EBRT (91.7% vs. 75.4%, p = 0.014). On multivariable analysis, combo
RT (hazard ratio, 0.48; 95% confidence interval: 0.25, 0.92; p = 0.03) was
associated with improved bRFS. Combo-RT had significantly improved bRFS compared
with EBRT in the unfavorable subgroup (p = 0.02) but not in the favorable
subgroup (p = 0.37). DMFS was similar within the entire cohort and by risk group.
Combo-RT was associated with an increased rate in the 6-year cumulative incidence
of Grade 3 GU toxicity (hazard ratio, 3.48; 95% confidence interval: 1.1, 11.1; p
= 0.026); however, 57% of Grade 3 GU toxicity was resolved, 29% had partial
improvement, and only 1 patient had persistent Grade 3 GU toxicity. CONCLUSIONS:
In intermediate-risk prostate cancer, combo-RT improved bRFS but not DMFS and
increased Grade 3 GU toxicity. The bRFS benefit was limited to unfavorable
intermediate-risk patients.
PMID- 28499488
TI - In vivo dosimetry with alanine/electron spin resonance dosimetry to evaluate the
urethra dose during high-dose-rate brachytherapy.
AB - PURPOSE: To determine the dose of the urethra during Ir-192 high-dose-rate
brachytherapy in 15 patients, a new detector form developed for in vivo
measurements was used as described by Anton et al. 2009. METHODS AND MATERIALS:
The detector consists of alanine powder with paraffin as binder which was filled
in a shrinkable tube for measurements. The alanine strand so produced was
inserted in the foley catheter during high-dose-rate brachytherapy of the
prostate. The measured dose was compared with the dose calculated by the
treatment planning system SWIFT for 15 patients. After 8 patients, a marker was
introduced for better positioning of the alanine strand using transrectal
ultrasound images. RESULTS: The measurements of the dose of the urethra agreed
very well with the dose calculated by SWIFT within the estimated standard
uncertainty of the method for 8 patients with a mean absolute deviation of 0.08
Gy. However, for the other 7 patients, a mean absolute deviation between
delivered and measured dose of -5.13 Gy was seen. For these patients, the active
volume of the alanine dosimeter could not properly be reconstructed on the
ultrasound images. CONCLUSION: The method presented in this study is useful for
quality control of irradiations in vivo. To reconstruct the active volume on the
corresponding ultrasound images, the correct application of the alanine strand in
the urethra is very important. This procedure needs a well-trained physician.
PMID- 28499489
TI - Neuronal PAS Domain Proteins 1 and 3 Are Master Regulators of Neuropsychiatric
Risk Genes.
AB - BACKGROUND: NPAS3 has been established as a robust genetic risk factor in major
mental illness. In mice, loss of neuronal PAS domain protein 3 (NPAS3) impairs
postnatal hippocampal neurogenesis, while loss of the related protein NPAS1
promotes it. These and other findings suggest a critical role for NPAS proteins
in neuropsychiatric functioning, prompting interest in the molecular pathways
under their control. METHODS: We used RNA sequencing coupled with chromatin
immunoprecipitation sequencing to identify genes directly regulated by NPAS1 and
NPAS3 in the hippocampus of wild-type, Npas1-/-, and Npas3-/- mice. Computational
integration with human genetic and expression data revealed the disease relevance
of NPAS-regulated genes and pathways. Specific findings were confirmed at the
protein level by Western blot. RESULTS: This is the first in vivo, transcriptome
scale investigation of genes regulated by NPAS1 and NPAS3. These transcription
factors control an ensemble of genes that are themselves also major regulators of
neuropsychiatric function. Specifically, Fmr1 (fragile X syndrome) and Ube3a
(Angelman syndrome) are transcriptionally regulated by NPAS3, as is the
neurogenesis regulator Notch. Dysregulation of these pathways was confirmed at
the protein level. Furthermore, NPAS1/3 targets show increased human genetic
burden for schizophrenia and intellectual disability. CONCLUSIONS: Together,
these data provide a clear, unbiased view of the full spectrum of genes regulated
by NPAS1 and NPAS3 and show that these transcription factors are master
regulators of neuropsychiatric function. These findings expose the molecular
pathophysiology of NPAS1/3 mutations and provide a striking example of the
shared, combinatorial nature of molecular pathways that underlie diagnostically
distinct neuropsychiatric conditions.
PMID- 28499490
TI - Frequent inoculations with radiation attenuated sporozoite is essential for
inducing sterile protection that correlates with a threshold level of Plasmodia
liver-stage specific CD8+ T cells.
AB - Whole sporozoite vaccine (WSV) is shown to induce sterile protection that targets
Plasmodium liver-stage infection. There are many underlying issues associated
with induction of effective sterile protracted protection. In this study, we have
addressed how the alterations in successive vaccine regimen could possibly affect
the induction of sterile protection. We have demonstrated that the pattern of
vaccination with RAS (radiation attenuated sporozoites) induces varying degrees
of protection among B6 mice. Animals receiving four successive doses generated
100% sterile protection. However, three successive doses, though with the same
parasite inoculum as four doses, could induce sterile protection in ~50% mice.
Interestingly, mice immunized with the same 3 doses, but with longer gap, could
not survive the challenge. We demonstrate that degree of protection correlates
with the frequencies of IFN-gamma+ and multifunctional (IFN-gamma+ CD107a+) CD8+
TEM cells present in liver. The failure to achieve protective threshold frequency
of these cells in liver might make the host more vulnerable to parasite infection
during infectious sporozoite challenge.
PMID- 28499492
TI - Mechanisms and Dynamics of T Cell-Mediated Cytotoxicity In Vivo.
AB - Cytotoxic T lymphocytes (CTLs) are critical in the elimination of infected or
malignant cells and are emerging as a major therapeutic target. How CTLs
recognize and kill harmful cells has been characterized in vitro but little is
known about these processes in the living organism. Here we review recent
insights into CTL-mediated killing with an emphasis on in vivo CTL biology.
Specifically, we focus on the possible rate-limiting steps determining the
efficiency of CTL-mediated killing. We also highlight the need for cell-based
datasets that permit the quantification of CTL dynamics, including CTL location,
migration, and killing rates. A better understanding of these factors is required
to predict protective CD8 T cell immunity in vivo and to design optimized
vaccination protocols.
PMID- 28499493
TI - Bifunctional dentifrice: Amorphous polyphosphate a regeneratively active sealant
with potent anti-Streptococcus mutans activity.
AB - OBJECTIVE: In this study we demonstrate that inorganic polyphosphate (polyP)
exhibits a dual protective effect on teeth: it elicits a strong antibacterial
effect against the cariogenic bacterium Streptococcus mutans and, in form of
amorphous calcium polyP microparticles (size of 100-400nm), it efficiently
reseals cracks/fissures in the tooth enamel and dentin. METHODS: Three different
formulations of amorphous polyP microparticles (Ca-polyP, Zn-polyP and Sr-polyP)
were prepared. RESULTS: Among the different polyP microparticles tested, the Ca
polyP microparticles, as a component of a newly developed formulation of a
dentifrice, turned out to be most effective in inhibiting growth of S. mutans.
Further studies have shown that it is mainly the soluble polyP, which has a
strong antibacterial activity, either given as sodium salt of polyP or formed by
partial disintegration of the microparticles via the alkaline phosphatase present
in the oropharyngeal cavity. In addition, we demonstrate that the developed
toothpaste containing incorporated amorphous polyP microparticles, efficiently
reduces dental biofilm formation. SIGNIFICANCE: From our results we conclude that
polyP microparticles, if added to toothpaste in an amorphous state, might be
beneficial not only for restoring tooth damages but also because they provide a
suitable depot of functionally/antibacterially active soluble polyP.
PMID- 28499494
TI - Corrigendum to "Take a look at the bright side: Effects of positive body exposure
on selective visual attention in women with high body dissatisfaction" [Behav.
Res. Therapy 83 (2016) 19-25].
PMID- 28499495
TI - Distraction/Suppression and Distress Endurance diminish the extent to which
generalized conditioned fear is associated with maladaptive behavioral avoidance.
AB - A central conditioning correlate of clinical anxiety is the over-generalization
of Pavlovian fear to safe stimuli resembling conditioned danger cues (CS+).
Though much of the pathogenic influence of such generalization may lie in the
unnecessary behavioral avoidance it evokes, few studies have examined maladaptive
avoidance associated with Pavlovian generalization. Lab-based assessments of this
process, here referred to as instrumental avoidance from Pavlovian generalization
(IAP-G), have recently begun. The current study represents a next step in this
line of work by examining personality factors that may reduce maladaptive IAP-G.
This is a clinically relevant effort, as such traits may reflect resilience
factors, with high levels reducing the likelihood of maladaptive generalized
avoidance following Pavlovian generalization. Here we focus on the effects of
Distraction/Suppression (DS) and Distress Endurance (DE) on IAP-G. Results
indicate that both DS and DE moderate IAP-G by weakening relations between
Pavlovian generalization of fear-potentiated startle and maladaptive generalized
avoidance. Further, moderating effects of DS were most pronounced for more
ambiguous cues of threat (i.e., stimuli moderately resembling CS+), while
moderating effects of DE were most pronounced for more certain cues of threat
(i.e., stimuli highly resembling CS+, as well as the CS + itself). Results
implicate DS and DE as protective factors against the maladaptive behavioral
consequences of Pavlovian generalization, and further indicate that the
protective influence of these traits may depend on the ambiguity of the threat at
hand.
PMID- 28499496
TI - Relationships Between Quantitative Pulse-Echo Ultrasound Parameters from the
Superficial Zone of the Human Articular Cartilage and Changes in Surface
Roughness, Collagen Content or Collagen Orientation Caused by Early Degeneration.
AB - We aimed to quantitatively investigate the relationship between amplitude-based
pulse-echo ultrasound parameters and early degeneration of the knee articular
cartilage. Twenty samples from six human femoral condyles judged as grade 0 or 1
according to International Cartilage Repair Society grading were assessed using a
15-MHz pulsed-ultrasound 3-D scanning system ex vivo. Surface roughness (Rq),
average collagen content (A1) and collagen orientation (A12) in the superficial
zone of the cartilage were measured via laser microscopy and Fourier transform
infrared imaging spectroscopy. Multiple regression analysis with a linear mixed
effects model (LMM) revealed that a time-domain reflection coefficient at the
cartilage surface (Rc) had a significant coefficient of determination with Rq and
A12 (RLMMm2=0.79); however, Rc did not correlate with A1. Concerning the collagen
characteristic in the superficial zone, Rc was found to be a sensitive indicator
reflecting collagen disorganization, not collagen content, for the early
degeneration samples.
PMID- 28499497
TI - A sensitive chemiluminescence enzyme immunoassay based on molecularly imprinted
polymers solid-phase extraction of parathion.
AB - The chemiluminescence enzyme immunoassay (CLEIA) method responds differently to
various sample matrices because of the matrix effect. In this work, the CLEIA
method was coupled with molecularly imprinted polymers (MIPs) synthesized by
precipitation polymerization to study the matrix effect. The sample recoveries
ranged from 72.62% to 121.89%, with a relative standard deviation (RSD) of 3.74
18.14%.The ratio of the sample matrix-matched standard curve slope rate to the
solvent standard curve slope was 1.21, 1.12, 1.17, and 0.85 for apple, rice,
orange and cabbage in samples pretreated with the mixture of PSA and C18.
However, the ratio of sample (apple, rice, orange, and cabbage) matrix-matched
standard-MIPs curve slope rate to the solvent standard curve was 1.05, 0.92,
1.09, and 1.05 in samples pretreated with MIPs, respectively. The results
demonstrated that the matrices of the samples greatly interfered with the
detection of parathion residues by CLEIA. The MIPs bound specifically to the
parathion in the samples and eliminated the matrix interference effect.
Therefore, the CLEIA method have successfully applied MIPs in sample pretreatment
to eliminate matrix interference effects and provided a new sensitive assay for
agro-products.
PMID- 28499498
TI - Aptatope mapping of the binding site of a progesterone aptamer on the steroid
ring structure.
AB - In this work we report the mapping of the binding site of the only progesterone
aptamer published to date, in an approach referred to as aptatope mapping. By
linking the binding data obtained from microscale thermophoresis analysis to the
structural differences on the ring structure of a range of steroids, we
elucidated the moieties involved in aptamer-progesterone binding. This approach
can be further exploited for the characterization of aptamer specificity and
ultimately facilitate the development of aptamer-based assays depending on the
desired specificity.
PMID- 28499499
TI - Heat-related morbidity and mortality in New England: Evidence for local policy.
AB - BACKGROUND: Heat-related morbidity and mortality is a recognized public health
concern. However, public health officials need to base policy decisions on local
evidence, which is often lacking for smaller communities. OBJECTIVES: To evaluate
the association between maximum daily heat index (HI) and morbidity and mortality
in 15 New England communities (combined population: 2.7 million) in order to
provide actionable evidence for local officials. METHODS: We applied
overdispersed Poisson nonlinear distributed lag models to evaluate the
association between HI and daily (May-September) emergency department (ED)
admissions and deaths in each of 15 study sites in New Hampshire, Maine, and
Rhode Island, controlling for time trends, day of week, and federal holidays.
Site-specific estimates were meta-analyzed to provide regional estimates.
RESULTS: Associations (sometimes non-linear) were observed between HI and each
health outcome. For example, a day with a HI of 95 degrees F vs. 75 degrees F was
associated with a cumulative 7.5% (95% confidence interval [CI]: 6.5%, 8.5%) and
5.1% (95% CI: 0.2%, 10.3%) higher rate of all-cause ED visits and deaths,
respectively, with some evidence of regional heterogeneity. We estimate that in
the study area, days with a HI>=95 degrees F were associated with an annual
average of 784 (95% CI: 658, 908) excess ED visits and 22 (95% CI: 3, 39) excess
deaths. CONCLUSIONS: Our results suggest the presence of adverse health impacts
associated with HI below the current local guideline criteria of HI>=100 degrees
F used to issue heat advisories. We hypothesize that lowering this threshold may
lead to substantially reduced heat-related morbidity and mortality in the study
area.
PMID- 28499500
TI - Ca2+ Release Channels Join the 'Resolution Revolution'.
AB - Ryanodine receptors (RyRs) are calcium release channels expressed in the
sarcoendoplasmic reticula of many cell types including cardiac and skeletal
muscle cells. In recent years Ca2+ leak through RyRs has been implicated as a
major contributor to the development of diseases including heart failure, muscle
myopathies, Alzheimer's disease, and diabetes, making it an important therapeutic
target. Recent mammalian RyR1 cryoelectron microscopy (cryo-EM) structures of
multiple functional states have clarified longstanding questions including the
architecture of the transmembrane (TM) pore and cytoplasmic domains, the location
and architecture of the channel gate, ligand-binding sites, and the gating
mechanism. As we advance toward complete models of RyRs this new information
enables the determination of domain-domain interfaces and the location and
structural effects of disease-causing RyR mutations.
PMID- 28499501
TI - Potential involvement of chondroitin sulfate A in the pathogenesis of
ameloblastoma.
AB - Ameloblastoma is classified as a benign odontogenic tumor characterized by
locally invasive behavior and high risk of recurrence. Here, we evaluate a
potential role for glycosaminoglycan, a structural component of cell membranes
and extracellular matrix, in ameloblstoma pathogenesis. We subjected formalin
fixed, paraffin-embedded tissue sections of 34 cases of ameloblastoma, 10 of
odontogenic keratocyst, and 17 of dentigerous cyst to immunohistochemistry using
monoclonal antibodies recognizing chondroitin sulfate A (CS-A), heparan sulfate
(HS), and keratan sulfate (KS). Expression levels of CS-A in epithelial component
and stroma of ameloblastoma were significantly higher than those in odontogenic
keratocyst and dentigerous cyst. Moreover, CS-A in ameloblastoma was more
strongly expressed in stellate reticulum-like cells than in amelobast-like cells
with statistical significance. On the other hand, expression levels of HS and KS
in epithelial component and stroma of ameloblastoma were lower compared with CS
A. These results overall reveal that among these odontogenic lesions, CS-A is
preferentially expessed in ameloblastoma, suggesting potential pathogenetic role
probably in cytodifferention of tumor cells to stellate reticulum-like cells.
PMID- 28499502
TI - Sesamin encouraging effects on chondrogenic differentiation of human amniotic
fluid-derived mesenchymal stem cells.
AB - Worldwide, the most recognized musculoskeletal degenerative disease is
osteoarthritis (OA). Sesamin, a major abundant lignan compound present in Sesamun
Indicum Linn, has been described for its various pharmacological effects and
health benefits. However, the promoting effects of sesamin on chondrogenic
differentiation have not yet been observed. Herein, the aim of this study was to
investigate the effects of sesamin on cell cytotoxicity and the potent supporting
effects on chondrogenic differentiation of human amniotic fluid-derived
mesenchymal stem cells (hAF-MSCs). The results indicated that sesamin was not
toxic to hAF-MSCs after sesamin treatment. When treating the cells with a
combination of sesamin and inducing factors, sesamin was able to up-regulate the
expression level of specific genes which play an essential role during the
cartilage development process, including SOX9, AGC, COL2A1, COL11A1, and COMP and
also simultaneously promote the cartilage extracellular protein synthesis,
aggrecan and type II collagen. Additionally, histological analysis revealed a
high amount of accumulated sGAG staining inside the porous scaffold in the
sesamin co-treating group. In conclusion, the results of this study have
indicated that sesamin can be considered a chondrogenic inducing factor and a
beneficial dietary supplement for cartilage repair.
PMID- 28499503
TI - Mast cells in neuroinflammation and brain disorders.
AB - It is well recognized that neuroinflammation is involved in the pathogenesis of
various neurodegenerative diseases. Microglia and astrocytes are major pathogenic
components within this process and known to respond to proinflammatory mediators
released from immune cells such as mast cells. Mast cells reside in the brain and
are an important source of inflammatory molecules. Mast cell interactions with
glial cells and neurons result in the release of mediators such as cytokines,
proteases and reactive oxygen species. During neuroinflammation, excessive levels
of these mediators can influence neurogenesis, neurodegeneration and blood-brain
barrier (BBB) permeability. Mast cells are considered first responders and are
able to initiate and magnify immune responses in the brain. Their possible role
in neurodegenerative disorders such as multiple sclerosis, Alzheimer's disease
and autism has gained increasing interest. We discuss the possible involvement of
mast cells and their mediators in neurogenesis, neurodegeneration and BBB
permeability and their role in neuronal disorders such as cerebral ischemia,
traumatic brain injury, neuropathic pain, multiple sclerosis, Alzheimer's
disease, migraine, autism, and depression.
PMID- 28499504
TI - Williams syndrome deletions and duplications: Genetic windows to understanding
anxiety, sociality, autism, and schizophrenia.
AB - We describe and evaluate an integrative hypothesis for helping to explain the
major neurocognitive features of individuals with Williams syndrome region
deletions and duplications. First, we demonstrate how the cognitive differences
between Williams syndrome individuals, individuals with duplications of this
region, and healthy individuals parallel the differences between individuals
subject to effects of increased or decreased oxytocin. Second, we synthesize
evidence showing that variation in expression of the gene GTF2I (General
Transcription Factor II-I) underlies the primary social phenotypes of Williams
syndrome and that common genetic variation in GTF2I mediates oxytocin reactivity,
and its correlates, in healthy populations. Third, we describe findings relevant
to the hypothesis that the GTF2I gene is subject to parent of origin effects
whose behavioral expression fits with predictions from the kinship theory of
genomic imprinting. Fourth, we describe how Williams syndrome can be considered,
in part, as an autistic syndrome of Lorna Wing's 'active-but-odd' autism subtype,
in contrast to associations of duplications with both schizophrenia and autism.
PMID- 28499505
TI - Multiple central giant cell tumour lesions are exclusively linked to syndromes
related to RAS/MAPK pathway anomalies.
PMID- 28499506
TI - Influence of implant location in patients with and without type 2 diabetes
mellitus: 2-year follow-up.
AB - The aim of the present cross-sectional retrospective 2-year follow-up clinical
study was to assess the influence of implant location on clinical and
radiographic parameters around dental implants placed in patients with and
without type 2 diabetes mellitus (T2DM). Twenty-seven patients with T2DM and 25
non-diabetic controls were included. Implants were classified into three zones
according to their location: (1) anterior zone: implant/s replacing anterior
teeth, (2) middle zone: implant/s replacing premolars, and (3) posterior zone:
implant/s replacing molars. Peri-implant bleeding on probing (BOP), probing depth
(PD), and crestal bone loss (CBL) were measured. P-values less than 0.05 were
considered statistically significant. The mean age of patients with T2DM was 42.5
years and that of non-diabetic controls was 40.6 years. The mean fasting blood
glucose levels of patients with and without T2DM were 74.5mg/dl (66-80mg/dl) and
82.5mg/dl (79-88.1mg/dl), respectively. The mean duration of T2DM was 4.3 years.
There was no significant difference in BOP, PD, or CBL around implants placed in
any of the zones in the jaws of patients with and without T2DM. There is no
influence of implant location on clinical and radiographic parameters around
dental implants placed in patients with and without T2DM.
PMID- 28499507
TI - Nasolabial changes after two different approaches for surgically assisted rapid
maxillary expansion.
AB - This retrospective study evaluated the nasolabial changes in patients who
underwent surgically assisted rapid maxillary expansion (SARME) using two
different approaches. Nineteen patients were included in the study, divided into
two groups according to the kind of surgical approach performed: group 1 (n=9),
SARME performed through the standard Le Fort I circumvestibular approach followed
by the alar base cinch, and group 2 (n=10), SARME performed through a subtotal
vestibular approach associated to a V-shaped incision at the maxillary midline in
the labial frenulum region, without alar base cinch. Measurements of width,
length, and nasal projection as well as upper lip length were taken from cone
beam tomographic images obtained before surgery (T1) and 6 months postoperatively
(T2). Both groups presented an increase in the alar base width postoperatively
(P<0.05). The approach used in group 2 resulted in smaller changes in the alar
base width as measured at the superior alar curvature (P<0.05). Nasal length and
projection and upper lip length were not altered by SARME. The type of surgical
approach influenced nasolabial changes, but did not eliminate increase in width
of the alar base.
PMID- 28499508
TI - New approach to establish an object reference frame for dental arch in computer
aided surgical simulation.
AB - The purpose of this study was to develop a principal component analysis-based
adaptive minimum Euclidean distances (PAMED) approach to establish an optimal
object reference frame for symmetrical alignment of the dental arch during
computer-aided surgical simulation (CASS). It was compared with our triangular
methods and the standard principal component analysis (PCA) method. Thirty sets
of maxillary digital models were used. Midsagittal and occlusal planes were
ranked by three experienced evaluators based on their clinical judgment. The
results showed that for the midsagittal plane, all three evaluators ranked
"ideal" for all 30 models with the PAMED method, 28 with the triangular method,
and at least 11 with the PCA method. For the occlusal plane, one evaluator ranked
all 30 models "ideal" with both the PAMED and the PCA methods while the other two
evaluators ranked all 30 models "ideal" with the triangular method. However, the
differences among the three methods were minimal. In conclusion, our PAMED method
is the most reliable and consistent approach for establishing the object
reference frame for the dental arch in orthognathic surgical planning. The
triangular method should be used with caution because it can be affected by
dental arch asymmetry. The standard PCA method is not recommended.
PMID- 28499509
TI - Ten-year study of postoperative complications following dental extractions in
patients with inherited bleeding disorders.
AB - Dental extractions challenge the body's haemostatic mechanism. Postoperative
bleeding from dental extraction can be prolonged, or even life threatening in
patients with inherited bleeding disorders. Pre- and postoperative clotting
factor replacements or systemic desmopressin (ddAVP) have been advocated at our
institution to prevent bleeding complications in these patients. This study aimed
to assess the postoperative bleeding rate in patients with inherited bleeding
disorders that underwent dental extractions at our institution between 2003 and
2012. Patients with inherited bleeding disorders such as haemophilia A,
haemophilia B, and von Willebrand's disease were included. Retrospective chart
review was conducted. The result showed 53 extraction events occurred in 45
patients over the 10-year period. Ten out of 53 extraction events (18.9%) had
postoperative bleeding requiring further factor replacement or ddAVP.
Postoperative bleeding in one patient with mild haemophilia A was complicated by
the development of inhibitors. Type and severity of bleeding disorder, bone
removal, and use of a local haemostatic agent did not have any significant effect
on postoperative bleeding. Despite the use of perioperative factors and
desmopressin, the postoperative bleeding rates remain high for patients with
inherited bleeding disorders. More studies are required to assess the safety and
effectiveness of using local haemostatic control to achieve haemostasis following
extractions.
PMID- 28499511
TI - 73-Year-Old Asymptomatic Woman With Anemia.
PMID- 28499510
TI - Effect of Policy Change on the Use of Long-Distance Transport and Follow-Up Care
for Patients With Traumatic Finger Amputations.
AB - PURPOSE: In January 2006, the American College of Emergency Physicians released
updated guidelines for air transfer. Digit amputation and near-amputation were no
longer an indication for this costly service. We analyzed the effect of this
update on the use of air transport and associated care outcomes for finger
amputation patients and examined factors involved in providing follow-up care for
these patients. METHODS: A retrospective chart review identified all patients
treated for traumatic finger amputation between 1995 and 2012 at a major hand
trauma referral center. Analysis of available outcome measures was conducted
using multiple logistic and linear regression models. Analysis of factors
affecting frequency of return visits was performed via negative binomial
regression. RESULTS: We identified 724 patients with isolated traumatic finger
amputations. A total of 267 patients (37%) were transferred from an outside
hospital. Patients injured after 2006 were less likely to be transferred via air,
with a decrease from 29.5% pre-2006 to 14.9% post-2006. There was no difference
in likelihood of replantation success, length of hospital stay, or number of
return visits pre- versus post-2006. Patients transferred via helicopter after
2006 were more likely to be younger than 20 years of age and injured in a winter
month. Following successful replantation, work-relatedness was associated with a
higher number of return visits, whereas increasing age and transfer from farther
than 100 miles away were associated with fewer. CONCLUSIONS: After the American
College of Emergency Physicians policy update, decreased use of emergency air
transport to a hand trauma referral center for patients with traumatic finger
amputations did not adversely affect care delivery and outcomes. These changes
may be successfully implemented on a center-by-center basis to reduce costs
without detriment to patient care; however, coordination of follow-up care for
long-distance transport patients may require special focus when designing policy
around referral centers. TYPE PF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
PMID- 28499512
TI - The Organ Transplant Imperative.
AB - More than 120,000 US patients were listed for solid organ transplants in 2016.
Although data are scarce, we suspect that many of these patients will die while
awaiting transplant and without engaging in goals-of-care discussions with their
physicians. The challenges of addressing goals of care in patients with
malignancy, end-stage renal disease, and heart failure have been studied.
However, there is sparse literature on addressing goals of care throughout the
dynamic process of transplant assessment and listing. We propose the concept of
an organ transplant imperative, which is the perceived obligation by patients and
health care providers to proceed with organ transplant and to avoid advance care
planning and triggered goals-of-care discussions, even in situations in which
patients' clinical trajectories have worsened, resulting in poor quality of life
and low likelihood of meaningful survival. We situate this concept within the
paradigms of clinical inertia and the treatment and technological imperatives. We
illustrate this concept by describing a patient with end-stage liver disease
(ESLD) who was hoping for a liver transplant, who was caught between the
conflicting perspectives of specialist and primary care physicians, and who died
of complications of ESLD without experiencing the benefits of advance care
planning. Greater awareness of the transplant imperative should generate a shared
understanding among specialists, generalists, and patients and will provide
opportunities for more formalized involvement of palliative medicine experts in
the care of transplant patients.
PMID- 28499513
TI - Cardiorespiratory Fitness and All-Cause Mortality in Men With Emotional Distress.
AB - OBJECTIVE: Mental health and emotional disorders are often associated with higher
mortality risk. Whether higher cardiorespiratory fitness (CRF) reduces the risk
for all-cause mortality in individuals with emotional distress is not well known.
PATIENTS AND METHODS: Participants were 5240 men (mean age 46.5+/-9.5 years) with
emotional distress (including depression, anxiety, thoughts of suicide, or a
history of psychiatric or psychological counseling) who completed an extensive
medical examination between 1987 and 2002, and were followed for all-cause
mortality through December 31, 2003. Cardiorespiratory fitness was quantified as
maximal treadmill exercise test duration and was grouped for analysis as low,
moderate, and high. Cox proportional hazards regression was used to calculate
hazard ratios (HRs) and 95% CIs. RESULTS: During a median of 8.7 years (range,
1.0-16.9 years) and 46,217 person-years of follow-up, there were 128 deaths from
any cause. Age- and examination year-adjusted all-cause mortality rates per
10,000 person-years according to low, moderate, and high CRF groups were 64.7
(95% CI, 44.9-89.3), 28.0 (95% CI, 23.8-31.5), and 19.6 (95% CI, 17.1-21.6)
(trend P<.001) in men who reported any emotional distress. Overall, the
multivariable-adjusted HRs and 95% CIs across incremental CRF categories were
1.00 (referent), 0.54 (0.32-0.90), and 0.47 (0.26-0.85), linear trend P =.03.
CONCLUSION: Among men with emotional distress, higher CRF is associated with
lower risk of dying, independent of other clinical mortality predictors. Our
findings underscore the importance of promoting physical activity to maintain a
healthful level of CRF in individuals with emotional distress.
PMID- 28499514
TI - Needle Decompression of Tension Pneumothorax with Colorimetric Capnography.
AB - BACKGROUND: The success of needle decompression for tension pneumothorax is
variable, and there are no objective measures assessing effective decompression.
Colorimetric capnography, which detects carbon dioxide present within the pleural
space, may serve as a simple test to assess effective needle decompression.
METHODS: Three swine underwent traumatically induced tension pneumothorax
(standard of care, n = 15; standard of care with needle capnography, n = 15).
Needle thoracostomy was performed with an 8-cm angiocatheter. Similarly,
decompression was performed with the addition of colorimetric capnography.
Subjective operator assessment of decompression was recorded and compared with
true decompression, using thoracoscopic visualization for both techniques. Areas
under receiver operating curves were calculated and pairwise comparison was
performed to assess statistical significance (P < .05). RESULTS: The detection of
decompression by needle colorimetric capnography was found to be 100% accurate
(15 of 15 attempts), when compared with thoracoscopic assessment (true
decompression). Furthermore, it accurately detected the lack of tension
pneumothorax, that is, the absence of any pathologic/space-occupying lesion, in
100% of cases (10 of 10 attempts). Standard of care needle decompression was
detected by operators in 9 of 15 attempts (60%) and was detected in 3 of 10
attempts when tension pneumothorax was not present (30%). True decompression,
under direct visualization with thoracoscopy, occurred 15 of 15 times (100%) with
capnography, and 12 of 15 times (80%) without capnography. Areas under receiver
operating curves were 0.65 for standard of care and 1.0 for needle capnography (P
= .002). CONCLUSIONS: Needle decompression with colorimetric capnography provides
a rapid, effective, and highly accurate method for eliminating operator bias for
tension pneumothorax decompression. This may be useful for the treatment of this
life-threatening condition.
PMID- 28499516
TI - Improving CPR Performance.
AB - Cardiac arrest continues to represent a public health burden with most patients
having dismal outcomes. CPR is a complex set of interventions requiring
leadership, coordination, and best practices. Despite the widespread adoption of
new evidence in various guidelines, the provision of CPR remains variable with
poor adherence to published recommendations. Key steps health-care systems can
take to enhance the quality of CPR and, potentially, to improve outcomes, include
optimizing chest compressions, avoiding hyperventilation, encouraging
intraosseous access, and monitoring capnography. Feedback devices provide
instantaneous guidance to the rescuer, improve rescuer technique, and could
impact patient outcomes. New technologies promise to improve the resuscitation
process: mechanical devices standardize chest compressions, capnography guides
resuscitation efforts and signals the return of spontaneous circulation, and
intraosseous devices minimize interruptions to gain vascular access. This review
aims at identifying a discreet group of interventions that health-care systems
can use to raise their standard of cardiac resuscitation.
PMID- 28499515
TI - Incidence of Pneumonitis With Use of Programmed Death 1 and Programmed Death
Ligand 1 Inhibitors in Non-Small Cell Lung Cancer: A Systematic Review and Meta
Analysis of Trials.
AB - BACKGROUND: Programmed death 1 (PD-1) programmed death-ligand 1 (PD-L1)
inhibitors show significant clinical activity in non-small cell lung carcinoma
(NSCLC). However, they are often associated with potentially fatal immune
mediated pneumonitis. Preliminary reports of trials suggest a difference in the
rate of pneumonitis with PD-1 and PD-L1 inhibitors. We sought to determine the
overall incidence of pneumonitis and differences according to type of inhibitors
and prior chemotherapy use. METHODS: MEDLINE, Embase, and Scopus databases were
searched up to November 2016. Rates of pneumonitis of any grade and grade >= 3
from all clinical trials investigating nivolumab, pembrolizumab, atezolizumab,
durvalumab, and avelumab as single agents in NSCLC were collected. The incidence
of pneumonitis across trials was calculated using DerSimonian-Laird random
effects models. We compared incidences between PD-1 and PD-L1 inhibitors and
between treatment naive and previously treated patients. RESULTS: Nineteen trials
(12 with PD-1 inhibitors [n = 3,232] and 7 with PD-L1 inhibitors [n = 1,806])
were identified. PD-1 inhibitors were found to have statistically significant
higher incidence of any grade pneumonitis compared with PD-L1 inhibitors (3.6%;
95% CI, 2.4%-4.9% vs 1.3%; 95% CI, 0.8%-1.9%, respectively; P = .001). PD-1
inhibitors were also associated with higher incidence of grade 3 or 4 pneumonitis
(1.1%; 95% CI, 0.6%-1.7% vs 0.4%; 95% CI, 0%-0.8%; P = .02). Treatment naive
patients had higher incidence of grade 1 through 4 pneumonitis compared with
previously treated patients (4.3%; 95% CI, 2.4%-6.3% vs 2.8%; 95% CI, 1.7%- 4%; P
= .03). CONCLUSIONS: There was a higher incidence of pneumonitis with use of PD-1
inhibitors compared with PD-L1 inhibitors. Higher rate of pneumonitis was more
common in treatment naive patients.
PMID- 28499517
TI - Post-Orgasmic Illness Syndrome: Where Are We?
PMID- 28499518
TI - Combined Artificial Urinary Sphincter and Penile Implant Surgery: Good or Bad
Idea?
PMID- 28499519
TI - Association Between Sexual Problems and Relationship Satisfaction Among People
With Cardiovascular Disease.
AB - BACKGROUND: Relationship satisfaction is generally positively correlated with
sexual satisfaction, but this relation has been poorly examined in people with
cardiovascular disease who are at increased risk of sexual problems compared with
the general population. AIM: To document reported changes to sex after a
diagnosis of cardiac disease and determine whether there is an association
between sexual function and relationship satisfaction. METHODS: Semistructured
telephone interviews focused on relationship satisfaction and sexual problems
were conducted with 201 people with cardiovascular disease who were currently in
a sexual relationship with one main partner and were recruited from six hospital
cardiac rehabilitation centers in Ireland. Comparisons between groups were
conducted using t-tests and multivariate analysis of variance for continuous
variables and chi2 tests for categorical variables. Predictors of relationship
satisfaction were assessed using multiple linear regression analysis. OUTCOMES:
Data were gathered on demographic and clinical variables, sexual problems, and
relationship satisfaction, including satisfaction with the physical, emotional,
affection, and communication aspects of relationships. RESULTS: Just less than
one third of participants (n = 61, 30.3%) reported that sex had changed for the
worse since their cardiac event or diagnosis, with approximately half of these
stating that this was a serious problem for them. Satisfaction with relationships
was high among patients surveyed; more than 70% of the sample reported being very
or extremely satisfied with the physical and emotional aspects and showing
affection during sex. Satisfaction with communication about sex was lower, with
only 58% reporting being very or extremely satisfied. We did not find significant
associations between reporting of sexual problems or deterioration of sex as a
result of disease and relationship satisfaction. CLINICAL IMPLICATIONS: Cardiac
rehabilitation programs should address these sexual problems, potentially by
enhancing communication within couples about sex. STRENGTHS AND LIMITATIONS: The
strength is that data are presented on the sexual experiences and relationship
satisfaction of a relatively large sample of people diagnosed with cardiac
disease, a relatively underexplored research area. Limitations include the
possibility of selection bias of study participants and bias associated with self
report measurement. CONCLUSIONS: Sexual problems were significant in this
population but were not related to relationship satisfaction in this cross
sectional survey. Byrne M, Murphy P, D'Eath M, et al. Association Between Sexual
Problems and Relationship Satisfaction Among People With Cardiovascular Disease.
J Sex Med 2017;14:666-674.
PMID- 28499520
TI - Prevalence and Predictors of Low Sexual Desire, Sexually Related Personal
Distress, and Hypoactive Sexual Desire Dysfunction in a Community-Based Sample of
Midlife Women.
AB - BACKGROUND: Low desire is the most common sexual problem in women at midlife.
Prevalence data are limited by lack of validated instruments or exclusion of un
partnered or sexually inactive women. AIM: To document the prevalence of and
factors associated with low desire, sexually related personal distress, and
hypoactive sexual desire dysfunction (HSDD) using validated instruments. METHODS:
Cross-sectional, nationally representative, community-based sample of 2,020
Australian women 40 to 65 years old. OUTCOMES: Low desire was defined as a score
no higher than 5.0 on the desire domain of the Female Sexual Function Index
(FSFI); sexually related personal distress was defined as a score of at least
11.0 on the Female Sexual Distress Scale-Revised; and HSDD was defined as a
combination of these scores. The Menopause Specific Quality of Life Questionnaire
was used to document menopausal vasomotor symptoms. The Beck Depression Inventory
II was used to identify moderate to severe depressive symptoms (score >= 20).
RESULTS: The prevalence of low desire was 69.3% (95% CI = 67.3-71.3), that of
sexually related personal distress was 40.5% (95% CI = 38.4-42.6), and that of
HSDD was 32.2% (95% CI = 30.1-34.2). Of women who were not partnered or sexually
active, 32.4% (95% CI = 24.4-40.2) reported sexually related personal distress.
Factors associated with HSDD in an adjusted logistic regression model included
being partnered (odds ratio [OR] = 3.30, 95% CI = 2.46-4.41), consuming alcohol
(OR = 1.48, 95% CI = 1.16-1.89), vaginal dryness (OR = 2.08, 95% CI = 1.66-2.61),
pain during or after intercourse (OR = 1.63, 95% CI = 1.27-2.09), moderate to
severe depressive symptoms (OR = 2.69, 95% CI 1.99-3.64), and use of psychotropic
medication (OR = 1.42, 95% CI = 1.10-1.83). Vasomotor symptoms were not
associated with low desire, sexually related personal distress, or HSDD. CLINICAL
IMPLICATIONS: Given the high prevalence, clinicians should screen midlife women
for HSDD. STRENGTHS AND LIMITATIONS: Strengths include the large size and
representative nature of the sample and the use of validated tools. Limitations
include the requirement to complete a written questionnaire in English. Questions
within the FSFI limit the applicability of FSFI total scores, but not desire
domain scores, in recently sexually inactive women, women without a partner, and
women who do not engage in penetrative intercourse. CONCLUSIONS: Low desire,
sexually related personal distress, and HSDD are common in women at midlife,
including women who are un-partnered or sexually inactive. Some factors
associated with HSDD, such as psychotropic medication use and vaginal dryness,
are modifiable or can be treated with safe and effective therapies. Worsley R,
Bell RJ, Gartoulla P, Davis SR. Prevalence and Predictors of Low Sexual Desire,
Sexually Related Personal Distress, and Hypoactive Sexual Desire Dysfunction in a
Community-Based Sample of Midlife Women. J Sex Med 2017;14:675-686.
PMID- 28499521
TI - Investigating Clinically and Scientifically Useful Cut Points on the Compulsive
Sexual Behavior Inventory.
AB - INTRODUCTION: One of the major obstacles to conducting epidemiologic research and
determining the incidence and prevalence of compulsive sexual behavior (CSB) has
been the lack of relevant empirically derived cut points on the various
instruments that have been used to measure the concept. AIM: To further develop
the Compulsive Sexual Behavior Inventory (CSBI) through exploring predictive
validity and developing an empirically determined and clinically useful cut point
for defining CSB. METHODS: A sample of 242 men who have sex with men was
recruited from various sites in a moderate-size Midwestern city. Participants
were assigned to a CSB group or a control group using an interview for the
diagnosis that was patterned after the Structured Clinical Interview for the
Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition. The 22
item CSBI was administered as part of a larger battery of self-report
inventories. MAIN OUTCOME MEASURES: Receiver operating characteristic analyses
were used to compute area-under-the-curve measurements to ascertain the
predictive validity of the total scale, the control subscale, and the violence
subscale. Cut points were determined through consensus of experts balancing
sensitivity and specificity as determined by receiver operating characteristic
curves. RESULTS: Analyses indicated that the 22-item CSBI was a good predictor of
group membership, as was the 13-item control subscale. The violence subscale
added little to the predictive accuracy of the instrument; thus, it likely
measures something other than CSB. Two relevant cut points were found, one that
minimized false negatives and another, more conservative cut point that minimized
false positives. CONCLUSION: The CSBI as currently configured measures two
different constructions and only the control subscale is helpful in diagnosing
CSB. Therefore, we decided to eliminate the violence subscale and move forward
with a 13-item scale that we have named the CSBI-13. Two cut points were
developed from this revised scale, one that is useful as a clinical screening
tool and the other, more conservative measurement that is useful for etiologic
and epidemiologic research. Miner MH, Raymond N, Coleman E, Swinburne Romine R.
Investigating Clinically and Scientifically Useful Cut Points on the Compulsive
Sexual Behavior Inventory. J Sex Med 2017;14:715-720.
PMID- 28499522
TI - Editorial Comment on "Distinguishing Failure to Cure From Complication After
Penile Prosthesis Implantation".
PMID- 28499523
TI - Response and Rebuttal to Editorial Comment on "Distinguishing Failure to Cure
From Complication After Penile Prosthesis Implantation".
PMID- 28499524
TI - One-Stage Gender-Confirmation Surgery as a Viable Surgical Procedure for Female
to-Male Transsexuals.
AB - BACKGROUND: Female-to-male gender-confirmation surgery (GCS) includes removal of
breasts and female genitalia and complete genital and urethral reconstruction.
With a multidisciplinary approach, these procedures can be performed in one
stage, avoiding multistage operations. AIM: To present our results of one-stage
sex-reassignment surgery in female-to-male transsexuals and to emphasize the
advantages of single-stage over multistage surgery. METHODS: During a period of 9
years (2007-2016), 473 patients (mean age = 31.5 years) underwent metoidioplasty.
Of these, 137 (29%) underwent simultaneous hysterectomy, and 79 (16.7%) underwent
one-stage GCS consisting of chest masculinization, total transvaginal
hysterectomy with bilateral adnexectomy, vaginectomy, metoidioplasty, urethral
lengthening, scrotoplasty, and implantation of bilateral testicular prostheses.
All surgeries were performed simultaneously by teams of experienced gynecologic
and gender surgeons. OUTCOMES: Primary outcome measurements were surgical time,
length of hospital stay, and complication and reoperation rates compared with
other published data and in relation to the number of stages needed to complete
GCS. RESULTS: Mean follow-up was 44 months (range = 10-92). Mean surgery time was
270 minutes (range = 215-325). Postoperative hospital stay was 3 to 6 days (mean
= 4). Complications occurred in 20 patients (25.3%). Six patients (7.6%) had
complications related to mastectomy, and one patient underwent revision surgery
because of a breast hematoma. Two patients underwent conversion of transvaginal
hysterectomy to an abdominal approach, and subcutaneous perineal cyst, as a
consequence of colpocleisis, occurred in nine patients. There were eight
complications (10%) from urethroplasty, including four fistulas, three
strictures, and one diverticulum. Testicular implant rejection occurred in two
patients and testicular implant displacement occurred in one patient. CLINICAL
IMPLICATIONS: Female-to-male transsexuals can undergo complete GCS, including
mastectomy, hysterectomy, oophorectomy, vaginectomy, and metoidioplasty with
urethral reconstruction as a one-stage procedure without increased surgical risks
and complication rates. STRENGTHS AND LIMITATIONS: To our knowledge, this is the
largest cohort on this topic so far, with good surgical outcomes. Limitations
include lack of selection or exclusion criteria and lack of other studies with a
simple approach. For this reason, the technique should be studied further and
compared with other techniques for female-to-male surgery before it can be
recommended as an alternative procedure. CONCLUSIONS: Through a multidisciplinary
approach of experienced teams, one-stage GCS presents a safe, viable, and time-
and cost-saving procedure. Complication rates do not differ from reported rates
in multistage surgeries. Stojanovic B, Bizic M, Bencic M, et al. One-Stage Gender
Confirmation Surgery as a Viable Surgical Procedure for Female-to-Male
Transsexuals. J Sex Med 2017;14:741-746.
PMID- 28499525
TI - Consecutive Cyproterone Acetate and Estradiol Treatment in Late-Pubertal
Transgender Female Adolescents.
AB - BACKGROUND: Cyproterone acetate (CA) is an antiandrogenic progestin commonly used
in adult transwomen to suppress endogenous androgens, often in combination with
estrogens to induce feminization. AIM: To assess the (side) effects and
biochemical changes of CA alone and in combination with estrogens in adolescent
trans-girls. METHODS: This study was a retrospective analysis of clinical and
biochemical data from 27 trans-girls who presented at Tanner stage G4 and were
treated with CA monotherapy for at least 6 months (mean = 12 months) and then in
combination with incremental doses of estrogens (CA + E; mean = 16 months).
Statistical analysis of data included paired or unpaired Student t-test or
Wilcoxon signed-ranks or Mann-Whitney U-test as appropriate. OUTCOMES:
Anthropometrics, reported beneficial and side effects, safety parameters, and
hormone levels. RESULTS: Physical changes included decrease of facial and non
facial hair growth. One third showed breast development under CA (Tanner stages
B2-B3), which increased to Tanner stages B3 and B4 in 66.7% and 9.5%
respectively, during CA + E. Reported side effects during CA and CA + E were
breast tenderness, emotionality, fatigue, and flushes. No relevant weight changes
were observed. Main safety parameters showed the following changes. Hemoglobin
and hematocrit decreased and liver enzymes transiently and modestly increased
during CA. Triglycerides and cholesterol levels slightly decreased during CA but
returned to baseline during CA + E; glucose metabolism was unaffected. Relevant
hormonal changes included a decrease in gonadotropins during CA + E and in total
and free testosterone levels throughout treatment. Prolactin levels increased
during CA and were restored during CA + E. CLINICAL IMPLICATIONS: CA produced
modest feminizing effects in trans-girls and therefore might be a valuable
alternative in situations in which gonadotropin-releasing hormone analogues are
not the treatment of choice and/or are not reimbursed. STRENGTHS AND LIMITATIONS:
This is the first study to report on the effects of CA in the treatment of trans
girls and one of the few to report on the use of estrogens in this population.
Limitations are the modest sample size and the retrospective nature of this
study. CONCLUSION: Treatment with CA in late-pubertal trans-girls overall was
safe and well tolerated and induced mild clinical and biochemical feminizing
changes. Rapid further feminization was observed with incremental doses of E.
Tack LJW, Heyse R, Craen M, et al. Consecutive Cyproterone Acetate and Estradiol
Treatment in Late-Pubertal Transgender Female Adolescents. J Sex Med 2017;14:747
757.
PMID- 28499526
TI - Empirically Supported Incentive Model of Sexual Response Ignored.
PMID- 28499527
TI - Contraception: Menarche to Menopause.
AB - Contraception services should be part of routine health care maintenance in
reproductive-aged women, especially in light of the fact that approximately 50%
of pregnancies in the United States remain unplanned. Barrier methods, especially
condoms, may play a role in sexually transmitted disease prevention but are less
efficacious for pregnancy avoidance. There are several available hormonal
contraceptive options, including the combination hormonal pill, progestin-only
pill, combination hormonal patches and rings, injectable progestins, implantable
progestins, intrauterine devices (copper or progestin), and permanent
sterilization. These methods have varying efficacy, often related to patient
compliance or tolerance of side effects.
PMID- 28499528
TI - Vaginitis: Beyond the Basics.
AB - Vaginal complaints are one of the most common reasons women seek the advice of a
health care provider. Uncomplicated infections such as vulvovaginal candidiasis,
bacterial vaginosis, or trichomoniasis are easy to diagnose and treat. However,
about 8% of patients will have a more complicated course with failure to respond
to treatment or rapid recurrence of symptoms. Understanding the need for a
methodical, diagnostic approach to help these women with recurrent or refractory
cases of vaginal symptoms will aid the clinician achieve successful patient
outcomes.
PMID- 28499529
TI - Abnormal Uterine Bleeding: Current Classification and Clinical Management.
AB - Abnormal uterine bleeding is now classified and categorized according to the
International Federation of Gynecology and Obstetrics classification system: PALM
COEIN. This applies to nongravid women during their reproductive years and allows
more clear designation of causes, thus aiding clinical care and future research.
PMID- 28499530
TI - Recognition and Therapeutic Options for Malignancy of the Cervix and Uterus.
AB - An update on the current epidemiology and a review of the risk factors of
cervical and endometrial cancers are discussed. Cervical cancer prevention with a
focus on human papillomavirus vaccination and cervical cancer screening is
reviewed, emphasizing the new focus of less frequent intervention in an effort to
maintain high rates of early detection of disease while decreasing unnecessary
and anxiety-provoking colposcopies, biopsies, and excisional procedures. The
replacement of traditional endometrial hyperplasia terminology with more relevant
clinical categories, with an emphasis on the introduction of endometrial
intraepithelial neoplasia, is presented. Fertility-sparing options in the
management of early cervical and endometrial cancers are reviewed.
PMID- 28499531
TI - Gestational Diabetes: Diagnosis, Classification, and Clinical Care.
AB - Gestational diabetes mellitus (GDM) affects approximately 6% of pregnant women,
and prevalence is increasing in parallel with the obesity epidemic. Protocols for
screening/diagnosing GDM are controversial with several guidelines available.
Treatment of GDM results in a reduction in the incidence of preeclampsia,
shoulder dystocia, and macrosomia. If diet and lifestyle changes do not result in
target glucose levels, then treatment with metformin, glyburide, or insulin
should begin. It is generally recommended that pregnancies complicated by GDM do
not go beyond term. For women identified to have prediabetes, intensive lifestyle
intervention and metformin have been shown to prevent or delay progression to
type 2 diabetes.
PMID- 28499532
TI - Updates on the Recognition, Prevention and Management of Hypertension in
Pregnancy.
AB - Systematic reviews with meta-analysis represent the highest level of evidence
used to guide clinical practice. The defining criteria used to diagnose
preeclampsia have evolved, and will likely continue to evolve. Proteinuria is
sufficient but not necessary when defining preeclampsia. Hypertension without
proteinuria but with severe features is diagnostic. The methods used to measure
urinary protein have changed. The gold standard remains the 24-hour urine test.
The efficacy of low-dose aspirin in preventing preeclampsia is a function of
baseline risk. Data suggest that treating mild to moderate blood pressure has
clear maternal benefits with little fetal or neonatal risk.
PMID- 28499533
TI - Obstetric Emergencies: Shoulder Dystocia and Postpartum Hemorrhage.
AB - Shoulder dystocia and postpartum hemorrhage represent two of the most common
emergencies faced in obstetric clinical practice, both requiring prompt
recognition and management to avoid significant morbidity or mortality. Shoulder
dystocia is an uncommon, unpredictable, and unpreventable obstetric emergency and
can be managed with appropriate intervention. Postpartum hemorrhage occurs more
commonly and carries significant risk of maternal morbidity. Institutional
protocols and algorithms for the prevention and management of shoulder dystocia
and postpartum hemorrhage have become mainstays for clinicians. The goal of this
review is to summarize the diagnosis, incidence, risk factors, and management of
shoulder dystocia and postpartum hemorrhage.
PMID- 28499534
TI - Prenatal Diagnosis: Screening and Diagnostic Tools.
AB - The American Congress of Obstetricians and Gynecologists recommends that all
pregnant women be offered aneuploidy screening or diagnostic testing. A myriad of
screening and testing options are available to patients based on their risk
profile and gestational age. Screening options include traditional serum analyte
screening, such as first-trimester screening or quadruple screening, and more
recently, cell-free DNA. Diagnostic testing choices include chorionic villus
sampling and amniocentesis. The number of screening and diagnostic modalities
complicates prenatal counseling for physicians and can be difficult for patients
to grasp. Appropriate pretest and posttest counseling is important to ensure
adequate understanding of results and ensure testing strategy is concordant with
patient goals.
PMID- 28499535
TI - Cancer Recognition and Screening for Common Breast Disorders and Malignancy.
AB - Breast cancer is predicted to be the most common newly diagnosed cancer in women
in 2016. Screening mammography is the most commonly used method for the detection
of breast cancer in women of average risk. A genetic risk assessment is
recommended for women with a greater than 20% to 25% chance of having a
predisposition to breast and ovarian cancer. Evaluation of a breast mass begins
with a detailed history, assessment for cancer risk, and physical examination.
PMID- 28499536
TI - Recognizing and Managing Common Urogynecologic Disorders.
AB - Many women experience urogynecologic or pelvic floor disorders, especially
urinary incontinence and pelvic organ prolapse. The obstetrician/gynecologist is
often the first health care professional to evaluate and treat these disorders.
Treatments include pelvic floor muscle training, behavioral therapies, oral
medications, neuromodulation, intradetrusor medications, and surgery. When
approaching the woman with symptomatic prolapse, familiarity with pessaries and
various surgical procedures aid in counseling. Referral to a pelvic floor
physical therapist or to a female pelvic medicine and reconstructive surgeon
should be considered. Increasing attention to data on cost-effectiveness is a
necessity.
PMID- 28499537
TI - The Menopausal Transition.
AB - A clear understanding of the physiology of the menopausal transition, clinical
symptoms, and physical changes is essential for individualized patient
management, maximizing benefits and minimizing risks for the present and the
future. Menopause, defined by amenorrhea for 12 consecutive months, is determined
retrospectively and represents a permanent end to menses. Many physical changes
occur during the menopausal transition and beyond. Knowledge of symptoms and
findings experienced by women undergoing the menopausal transition allow
individualized care- improving quality of life and enhancing wellbeing for years
to come.
PMID- 28499538
TI - Burnout in Obstetricians and Gynecologists.
AB - It is estimated that 40% to 75% of obstetricians and gynecologists currently
suffer from professional burnout, making the lifetime risk a virtual certainty.
Although these statistics make for a dismal view of the profession, if the causes
and symptoms can be identified simple steps can be implemented to reverse the
threat. With a little care, the enjoyment of practice can be restored and the
sense of reward and the value of service can be returned.
PMID- 28499539
TI - Lifelong Learning Requires Maintenance of Knowledge.
PMID- 28499540
TI - Maintenance of Knowledge.
PMID- 28499541
TI - Sequence analysis of haemagglutinin and neuraminidase of H1N1 strain from a
patient coinfected with Mycobacterium tuberculosis.
AB - The 2009 H1N1 pandemic (H1N1pdm09) was associated with a considerable influenza
related morbidity and mortality. Among the complications, Mycobacterial
tuberculosis was recorded as a coinfection with influenza in rare cases. The full
length sequences of the viral haemagglutinin and neuraminidase of H1N1pdm09
influenza A virus were analyzed from a recently infected patient. The patient was
chronically infected with Mycobacterium tuberculosis. Molecular modelling and in
silico docking of the virus, and other selected strains with the drug oseltamivir
were conducted and compared. Sequence analysis of the viral haemagglutinin
revealed it to be closely related to the 6B.1 clade, with high identity to the
circulating H1N1pdm09 strains, and confirmed that the virus still harbouring high
affinity to the alpha-2,6-sialic acid human receptor. The viral neuraminidase
showed high identity to the neuraminidase of the recently circulating strains of
the virus with no evidence of the development of oseltamivir-resistant mutants.
Regular monitoring of the circulating strains is recommended to screen for a
possible emergence of drug-resistant strains.
PMID- 28499542
TI - Development of a taqman-based real-time PCR assay for the rapid and specific
detection of novel duck- origin goose parvovirus.
AB - A real-time PCR assay was developed for specific detection of novel duck-origin
goose parvovirus (N-GPV), the etiological agent of duck beak atrophy and dwarfism
syndrome (BADS). The detection limit of the assay was 102 copies. The assay was
useful in the prevention and control of BADS.
PMID- 28499543
TI - [Congenital anterior urethral diverticulum in children: A case report].
PMID- 28499544
TI - Diagnostic utility of cyclin D1 in the diagnosis of small round blue cell tumors
in children and adolescents: beware of cyclin D1 expression in clear cell sarcoma
of the kidney and CIC-DUX4 fusion-positive sarcomas. Comment on Magro et al
(2016).
PMID- 28499546
TI - Diagnostic utility of cyclin D1 in the diagnosis of small round blue cell tumors
in children and adolescents: beware of cyclin D1 expression in clear cell sarcoma
of the kidney and CIC-DUX4 fusion-positive sarcomas. Comment on Magro et al
(2016)-reply.
PMID- 28499545
TI - Mucoepidermoid carcinoma post-radioactive iodine treatment of papillary thyroid
carcinoma: unique presentation and putative etiologic association.
AB - We report the development of mucoepidermoid carcinomas of the parotid gland in 2
adult patients after a relatively short duration of radioactive iodine (RAI)
treatment of papillary thyroid carcinoma. Both instances, together with those
previously reported, underscore the selective nature of the mucoepidermoid
carcinoma phenotype development in patients with papillary thyroid carcinoma as a
consequence of RAI treatment. Efforts to alleviate salivary pathophysiologic
damage by RAI in these patients are warranted.
PMID- 28499547
TI - The dark side of T1 non-appendiceal small bowel neuroendocrine tumors.
PMID- 28499549
TI - Open letter to WHO DG candidates: reply from Sania Nishtar.
PMID- 28499548
TI - Mortality risks associated with emergency admissions during weekends and public
holidays: an analysis of electronic health records.
AB - BACKGROUND: Weekend hospital admission is associated with increased mortality,
but the contributions of varying illness severity and admission time to this
weekend effect remain unexplored. METHODS: We analysed unselected emergency
admissions to four Oxford University National Health Service hospitals in the UK
from Jan 1, 2006, to Dec 31, 2014. The primary outcome was death within 30 days
of admission (in or out of hospital), analysed using Cox models measuring time
from admission. The primary exposure was day of the week of admission. We
adjusted for multiple confounders including demographics, comorbidities, and
admission characteristics, incorporating non-linearity and interactions. Models
then considered the effect of adjusting for 15 common haematology and
biochemistry test results or proxies for hospital workload. FINDINGS: 257 596
individuals underwent 503 938 emergency admissions. 18 313 (4.7%) patients
admitted as weekday energency admissions and 6070 (5.1%) patients admitted as
weekend emergency admissions died within 30 days (p<0.0001). 9347 individuals
underwent 9707 emergency admissions on public holidays. 559 (5.8%) died within 30
days (p<0.0001 vs weekday). 15 routine haematology and biochemistry test results
were highly prognostic for mortality. In 271 465 (53.9%) admissions with complete
data, adjustment for test results explained 33% (95% CI 21 to 70) of the excess
mortality associated with emergency admission on Saturdays compared with
Wednesdays, 52% (lower 95% CI 34) on Sundays, and 87% (lower 95% CI 45) on public
holidays after adjustment for standard patient characteristics. Excess mortality
was predominantly restricted to admissions between 1100 h and 1500 h
(pinteraction=0.04). No hospital workload measure was independently associated
with mortality (all p values >0.06). INTERPRETATION: Adjustment for routine test
results substantially reduced excess mortality associated with emergency
admission at weekends and public holidays. Adjustment for patient-level factors
not available in our study might further reduce the residual excess mortality,
particularly as this clustered around midday at weekends. Hospital workload was
not associated with mortality. Together, these findings suggest that the weekend
effect arises from patient-level differences at admission rather than reduced
hospital staffing or services. FUNDING: NIHR Oxford Biomedical Research Centre.
PMID- 28499550
TI - Data linkage studies can help to explain the weekend effect.
PMID- 28499551
TI - Lessons learned from a single institution's retrospective analysis of emergent
cesarean delivery following external cephalic version with and without neuraxial
anesthesia.
AB - OBJECTIVES: To evaluate the risk of emergent cesarean delivery with the use of
neuraxial anesthesia for external cephalic version in a single practice.
BACKGROUND: Randomized trials have shown increased external cephalic version
success when neuraxial anesthesia is used, without additional risk. We
hypothesized that in our actual clinical practice, outside the confines of
randomized trials, neuraxial anesthesia could be associated with an increased
risk of emergent cesarean delivery. METHODS: This retrospective cohort study
included all women who underwent external cephalic version at a single
institution with and without neuraxial anesthesia. The primary outcome was the
incidence of emergent cesarean delivery (defined as delivery within 4hours of
version). Secondary outcomes were version success and ultimate mode of delivery.
RESULTS: A total of 135 women underwent external cephalic version procedures; 58
with neuraxial anesthesia (43.0%) and 77 without (57.0%). Location of the
procedure, tocolytic therapy, and gestational age were different between groups.
An increased rate of emergent cesarean delivery was found in procedures with
neuraxial anesthesia compared to procedures without (5/58 (8.6%) compared to 0/77
(0.0%); 95% CI for difference, 1.4 to 15.8%; P=0.013). CONCLUSION: In this single
hospital's practice, patients who may be at higher risk of complications and have
a lesser likelihood of success were provided NA for ECV. As a result, the use of
neuraxial anesthesia for external cephalic version was associated with a higher
rate of emergent cesarean delivery. Obstetric and anesthetic practices should
evaluate their patient selection and procedure protocol for external cephalic
version under neuraxial anesthesia.
PMID- 28499552
TI - Puerperal ventral epidural hematoma after epidural labor analgesia.
AB - Serious complications in obstetric anesthesia are a rare occurrence. High
neuraxial block, respiratory arrest in labor and delivery, and an unrecognized
spinal catheter are among the most frequently reported serious complications. A
serious complication occurs in approximately 1:3000 obstetric patients. Neuraxial
hematoma after obstetric epidural analgesia or anesthesia is extremely rare. We
present a case of a puerperal spinal epidural hematoma following epidural labor
analgesia. The patient presented with foot drop, which resolved after
conservative treatment. We reviewed the epidemiology, clinical manifestations and
treatment options for this rare complication.
PMID- 28499553
TI - Nasal delivery of Protollin-adjuvanted H5N1 vaccine induces enhanced systemic as
well as mucosal immunity in mice.
AB - Sporadic, yet frequent human infections with avian H5N1 influenza A viruses
continue to pose a potential pandemic threat. Poor immunogenicity of unadjuvanted
H5N1 vaccines warrants developing novel adjuvants and formulations as well as
alternate delivery systems to improve their immunogenicity and efficacy. Here, we
show that Protollin, a nasal adjuvant composed of Neisseria meningitides outer
membrane proteins non-covalently linked to Shigella flexneri 2a
lipopolysaccharide, is a potent nasal adjuvant for an inactivated split virion
H5N1 clade 1 A/Viet Nam1203/2004 (A/VN/1203/04) vaccine in a mouse model.
Protollin-adjuvanted vaccines elicited enhanced serum protective hemagglutination
inhibition titers, mucosal IgA responses, and H5N1-specific cell-mediated
immunity that resulted in complete protection against a lethal challenge with a
homologous virus as well as a heterologous clade 2 virus A/Indonesia/05/2005
(A/IN/05/05). Detailed analysis of adaptive immunity revealed that Protollin
increased the frequency of lymphoid- as well as local tissue-resident antibody
secreting cells, local germinal center reaction of B cells, broad-spectrum of CD4
T cell response. Our findings suggest that nasal delivery of H5N1 vaccine with
Protollin adjuvant can overcome the poor immunogenicity of H5N1 vaccines, induce
both cellular and humoral immune responses, enhance protection against challenge
with clade 1 and clade 2 H5N1 viruses and achieve significant antigen dose
sparing.
PMID- 28499554
TI - Effectiveness of HPV vaccines against genital warts in women from Valencia,
Spain.
AB - OBJECTIVES: To assess the effectiveness of the HPV vaccines in preventing genital
warts in young women. DESIGN: Population-based study using health databases.
SETTING: Valencian Community (Spain). PARTICIPANTS: All girls and women aged 14
19years who were registered in the Valencian Community between January 2009 and
December 2014 (n=279,787). MAIN OUTCOME MEASURES: Incident cases of genital warts
were defined as the first activation of diagnosis code ICD-9-CM 078.11 (Condyloma
acuminatum) in primary care and outpatient clinics during the study period.
RESULTS: There were 612 cases of genital warts. The overall incidence rate was
75.8/100,000 person-years (95% CrI 69.7-81.8). There was a decrease in genital
warts when female candidates to be vaccinated with quadrivalent HPV vaccine
reached the age of 18 (in 2012), compared to previous years. Incidence of genital
warts in unvaccinated women and those who received the bivalent vaccine was
higher than in girls and women who received the quadrivalent HPV vaccine. The
effectiveness of a three-dose regimen of the quadrivalent HPV vaccine was 77% (95
CrI: 66-85%), whereas that of a single dose was 61% (95 CrI: 20-87%). No
effectiveness was seen with a full vaccination course with the bivalent HPV
vaccine. CONCLUSIONS: Three doses of the quadrivalent HPV vaccine were effective
against genital warts in our population. Moreover, with low vaccine coverage the
incidence of genital warts decreased only in the vaccinated.
PMID- 28499555
TI - Evaluating biomechanics of user-selected sitting and standing computer
workstation.
AB - A standing computer workstation has now become a popular modern work place
intervention to reduce sedentary behavior at work. However, user's interaction
related to a standing computer workstation and its differences with a sitting
workstation need to be understood to assist in developing recommendations for use
and set up. The study compared the differences in upper extremity posture and
muscle activity between user-selected sitting and standing workstation setups.
Twenty participants (10 females, 10 males) volunteered for the study. 3-D
posture, surface electromyography, and user-reported discomfort were measured
while completing simulated tasks with each participant's self-selected
workstation setups. Sitting computer workstation associated with more non-neutral
shoulder postures and greater shoulder muscle activity, while standing computer
workstation induced greater wrist adduction angle and greater extensor carpi
radialis muscle activity. Sitting computer workstation also associated with
greater shoulder abduction postural variation (90th-10th percentile) while
standing computer workstation associated with greater variation for should
rotation and wrist extension. Users reported similar overall discomfort levels
within the first 10 min of work but had more than twice as much discomfort while
standing than sitting after 45 min; with most discomfort reported in the low back
for standing and shoulder for sitting. These different measures provide
understanding in users' different interactions with sitting and standing and by
alternating between the two configurations in short bouts may be a way of
changing the loading pattern on the upper extremity.
PMID- 28499556
TI - Reply to: "Pressure volume curves in cirrhosis: More than meets the eye".
PMID- 28499557
TI - The effect of focal cortical frontal and posterior lesions on recollection and
familiarity in recognition memory.
AB - Recognition memory can be subdivided into two processes: recollection (a
contextually rich memory) and familiarity (a sense that an item is old). The
brain network supporting recognition encompasses frontal, parietal and medial
temporal regions. Which specific regions within the frontal lobe are critical for
recollection vs. familiarity, however, are unknown; past studies of focal lesion
patients have yielded conflicting results. We examined patients with focal
lesions confined to medial polar (MP), right dorsal frontal (RDF), right
frontotemporal (RFT), left dorsal frontal (LDF), temporal, and parietal regions
and matched controls. A series of words and their humorous definitions were
presented either auditorily or visually to all participants. Recall, recognition,
and source memory were tested at 30 min and 24 h delay, along with
"remember/know" judgments for recognized items. The MP, RDF, temporal and
parietal groups were impaired on subjectively reported recollection; their intact
recognition performance was supported by familiarity. None of the groups were
impaired on cued recall, recognition familiarity or source memory. These findings
suggest that the MP and RDF regions, along with parietal and temporal regions,
are necessary for subjectively-reported recollection, while the LDF and right
frontal ventral regions, as those affected in the RTF group, are not.
PMID- 28499558
TI - Influence of response bias and internal/external source on lateral posterior
parietal successful retrieval activity.
AB - In studies of recognition memory, regions of the lateral posterior parietal
cortex exhibit greater activity (as indexed by the fMRI BOLD signal) during
correct recognition of "old" (studied) items than correct rejection of "new"
(unstudied) items. This effect appears to be source-sensitive, with greater
activity associated with recognition of perceived than imagined events. Parietal
successful retrieval activity also varies with response bias, or the tendency to
be conservative about making "old" judgments. Here, we examined whether
differences in response bias associated with recognition judgments of perceived
and imagined events could account for source-based differences in LPPC activity.
Participants perceived and imagined items in response to cue words and then at
test, made recognition judgments in blocks that knowingly contained either a high
or low proportion of old to new trials. While participants were indeed more
conservative when making judgments about perceived than imagined events, the
neuroimaging results demonstrated that response bias and source effects occurred
in non-overlapping parietal regions. These findings suggest that source-based
differences in LPPC activity cannot be explained by differences in response bias
associated with recognizing perceived and imagined events.
PMID- 28499559
TI - Identifying Psychosocial Distress and Stressors Using Distress-screening
Instruments in Patients With Localized and Advanced Penile Cancer.
AB - BACKGROUND: We examined the effects of treatment on the psychological well-being
of patients with localized or advanced penile cancer using screening
questionnaires to determine the consecutive need for psychosocial care. Penile
cancer is a rare, but highly aggressive, malignancy. The psychological stress of
patients with penile cancer arises from the cancer diagnosis per se and the
corresponding consequences of treatment. In addition, cancer-specific distress
results (eg, fear of metastasis, progression, relapse, death). Studies of the
psychosocial stress of penile cancer patients are rare. MATERIAL AND METHODS: We
undertook a prospective analysis of the data from patients with penile cancer who
had undergone surgery or chemotherapy from August 2014 to October 2016 at our
department. Patients were evaluated using standardized questionnaires for stress
screening and the identification for the need for psychosocial care (National
Comprehensive Cancer Network Distress Thermometer and Hornheider screening
instrument) and by assessing the actual use of psychosocial support. RESULTS: The
average stress level was 4.5. Of all the patients, 42.5% showed increased care
needs at the time of the survey. Younger patients, patients undergoing
chemotherapy, and patients with recurrence were significantly more integrated
with the psychosocial care systems. Finally, 67% of all patients received
inpatient psychosocial care. CONCLUSION: Owing to the potentially mutilating
surgery, patients with penile cancer experience increased psychological stress
and, consequently, have an increased need for psychosocial care. Therefore, the
emotional stress of these patients should be recognized and support based on
interdisciplinary collaboration offered.
PMID- 28499560
TI - The Challenge of Mental Health Care for Veterans and Their Families.
PMID- 28499561
TI - Grandmothers and Self-Management of Depressive Symptoms.
PMID- 28499562
TI - Educating Undergraduate Psychiatric Mental Health Nursing Students in Screening,
Brief Intervention, Referral to Treatment (SBIRT) Using an Online, Interactive
Simulation.
PMID- 28499563
TI - Roles of Psychiatry Nurses Within a Therapeutic Environment of Psychiatry Clinics
in Turkey.
AB - OBJECT: The object of this study is to determine the roles of psychiatry nurses
within the therapeutic environment of psychiatry clinics in Turkey. METHODS: This
study was performed in a cross-sectional and descriptive design in 195 institutes
comprising psychiatry clinics in Turkey. RESULTS: When the responsibilities of
nurses for clinical activities were asked, the following answers were obtained:
playing with patients or painting at a rate of 54,4%. It was determined that in
the majority of psychiatry clinics, there were educational activities which were
conducted by nurses. CONCLUSION: The researchers propose that the increase in the
roles and responsibilities of nurses in such activities be supported.
PMID- 28499564
TI - Socio-demographic and Psychological Correlates of Posttraumatic Growth among
Korean Americans with a History of Traumatic Life Experiences.
AB - This study examined socio-demographic and psychological correlates of
posttraumatic growth (PTG) among Korean Americans (KAs) with traumatic life
experiences. A total of 286 KAs were included. Being a woman or having a lower
annual household income had positive associations with PTG, while having no
religion had a negative association with it. In addition, praying and visiting a
mental health professional for coping with stress or for psychological problems
was positively associated with PTG. Higher resilience scores increased PTG, while
depressive symptoms decreased it. We suggest reinforcing help seeking behaviors
and accessibility to care facilities, and gender specific strengthening programs
for enhancing PTG among KAs.
PMID- 28499565
TI - Relationship Between Caregiving Burden and Anger Level in Primary Caregivers of
Individuals With Chronic Mental Illness.
AB - OBJECTIVES: The objective of this study was answer to the question: to what
extent are the anger of the caregivers of patients diagnosed with schizophrenia
and their perceived level of burden are related? METHOD: The study is a
descriptive and correlational study. The information form prepared by the
researchers which questions the socio-demographic information of the individuals
along with the "Caregiving Burden Inventory" which examines the burden of the
caregiver as well as "Trait Anger and Anger Expression Style Scale (TAAES)" which
determines the anger levels of the caregivers were used. RESULTS: The caregiving
burdens of the caregivers according to the score averages were determined as
11.88+/-9.78 for time and dependency burden, 11.93+/-8.46 for developmental
burden, 8.47+/-6.63 for physical burden, 5.61+/-5.26 for social burden, 6.29+/
5.25 for emotional burden and the total burden score was determined as 44.19+/
26.75. According to the trait anger and anger expression style scale score
averages; trait anger was determined as 15.12+/-5.95, anger expression as 9.70+/
3.43, anger-in as 15.22+/-4.02, anger control as 28.05+/-5.57 and anger total
score average as 68.11+/-9.97. CONCLUSION: According to the results obtained from
this study, caregivers of schizophrenia patients experience developmental,
physical, social and emotional burdens in addition to trait anger. The caregivers
of schizophrenia patients need knowledge and support in order to control the
burden and the anger they experience during the caregiving process.
PMID- 28499566
TI - Effects of Spiritual Group Therapy on Caregiver Strain in Home Caregivers of the
Elderly with Alzheimer's Disease.
AB - INTRODUCTION: Care of patients with Alzheimer's disease is one of the most
difficult types of care that exposes the caregiver to a high level of care
strain. The present research aimed at determining the effect of spiritual care on
caregiver strain of the elderly with Alzheimer's disease. METHODS: An
experimental study was carried out on 100 caregivers who were selected by
convenience sampling and randomly divided into intervention, control one and
control two groups. Group spiritual therapy was performed on the intervention
group for five weeks, Control one participate in the group sessions without any
particular interventions, and control two received no interventions. Data was
collected through a demographic questionnaire and Robinson's (1983) Caregiver
Strain Index, and analyzed using the Chi-square, Fisher's Exact test, one-way
analysis of variance and paired t-test. Statistical significance level was
considered as 0.05. RESULTS: In the intervention group mean of the posttest care
strain score 32.43+/-2.73 was significantly lower than pretest 37.16+/-1.26
(P<0.001). The mean posttest score of care strain was significantly lower in the
intervention group compared to the two other groups (P<0.001). CONCLUSION:
Spiritual care can reduce care strain in home caregivers of the elderly with
Alzheimer's disease.
PMID- 28499567
TI - The Effect of the Psychiatric Nursing Approach Based on the Tidal Model on Coping
and Self-esteem in People with Alcohol Dependency: A Randomized Trial.
AB - INTRODUCTION: People with alcohol dependency have lower self-esteem than controls
and when their alcohol use increases, their self-esteem decreases. Coping skills
in alcohol related issues are predicted to reduce vulnerability to relapse. It is
important to adapt care to individual needs so as to prevent a return to the
cycle of alcohol use. The Tidal Model focuses on providing support and services
to people who need to live a constructive life. AIM: The aim of the randomized
study was to determine the effect of the psychiatric nursing approach based on
the Tidal Model on coping and self-esteem in people with alcohol dependency.
METHOD: The study was semi-experimental in design with a control group, and was
conducted on 36 individuals (18 experimental, 18 control). An experimental and a
control group were formed by assigning persons to each group using the stratified
randomization technique in the order in which they were admitted to hospital. The
Coping Inventory (COPE) and the Coopersmith Self-Esteem Inventory (CSEI) were
used as measurement instruments. The measurement instruments were applied before
the application and three months after the application. In addition to routine
treatment and follow-up, the psychiatric nursing approach based on the Tidal
Model was applied to the experimental group in the One-to-One Sessions. RESULTS:
The psychiatric nursing approach based on the Tidal Model is an approach which is
effective in increasing the scores of people with alcohol dependency in positive
reinterpretation and growth, active coping, restraint, emotional social support
and planning and reducing their scores in behavioral disengagement. It was seen
that self-esteem rose, but the difference from the control group did not reach
significance. DISCUSSION: The psychiatric nursing approach based on the Tidal
Model has an effect on people with alcohol dependency in maintaining their
abstinence. IMPLICATIONS FOR PRACTICE: The results of the study may provide
practices on a theoretical basis for improving coping behaviors and self-esteem
and facilitating the recovery process of alcohol dependents with implications for
mental health nursing.
PMID- 28499568
TI - Risk Factors for Suicide Ideation Among Adolescents: Five-Year National Data
Analysis.
AB - This study identified risk factors for suicide ideation among adolescents through
a secondary analysis using data collected over five years from the 5th-9th Korea
Youth Risk Behavior Survey. We analyzed 370,568 students' responses to questions
about suicidality. The risk factors for suicide ideation included demographic
characteristics, such as gender (girls), low grades, low economic status, and not
living with one or both parents. Behavioral and mental health risk factors
affecting suicide ideation were depression, low sleep satisfaction, high stress,
alcohol consumption, smoking, and sexual activity. Health care providers should
particularly target adolescents manifesting the above risk factors when
developing suicide prevention programs for them.
PMID- 28499569
TI - Prevalence of Major Depression and Its Associations With Demographic and Clinical
Characteristics and Quality of Life in Chinese Patients With HBV-related Liver
Diseases.
AB - BACKGROUND: There are no data about the frequency of major depression in patients
with liver disease related to Hepatitis B virus (HBV) in China. This study
examined the prevalence of major depression and its clinical correlates and
association with quality of life (QOL) in patients with HBV-related liver
diseases. METHOD: Altogether 634 patients with HBV-related liver diseases met
study entry criteria and completed the survey. The diagnosis of major depression
was established with the Mini International Neuropsychiatric Interview (MINI).
Socio-demographic and clinical characteristics, Global Assessment of Functioning
(GAF) and QOL were measured. RESULTS: The prevalence of major depression was
6.4%. Multivariable logistic regression analyses revealed that insomnia (P=0.01,
OR=5.5, 95%CI=1.4-21.6) and global functioning (P<0.001, OR=0.6, 95% CI=0.5-0.7)
were independently associated with major depression. Major depression was
associated with both poor physical (F (1, 634)=4.0, P=0.04) and mental QOL (F (1,
634)=26.2, P<0.001). CONCLUSIONS: Given the negative impact of depression on
patients' QOL, more attempts should be made to identify and treat it in HBV
related diseases.
PMID- 28499570
TI - The Obsessive Compulsive Inventory-Child Version (OCI-CV): Further Evidence on
Confirmatory Factor Analytic Structure, Incremental and Criterion Validity in
Italian Community Children and Adolescents.
AB - Obsessive Compulsive Inventory-Child Version (OCI-CV) assesses six dimensions of
OCD symptoms in childhood and adolescence. The current study used confirmatory
methods to assess factor structure and reliability of the Italian OCI-CV in
community children and adolescents. 1408 community children and adolescents
completed the OCI-CV and a subgroup (n=855) completed measures of other anxiety
and depression symptoms. A six correlated factor structure showed good fit.
Reliability was excellent for total OCI-CV and for the other scales ranged from
good to acceptable. The OCI-CV confirmed good properties in terms of factor
structure and reliability.
PMID- 28499571
TI - Designing an Internet Intervention for Emerging Adults Who Experience Troubled
Relationships.
AB - This article describes how the Internet Intervention Model (IIM) was used as an
organizing framework to design a theoretically based Internet intervention for
emerging adults who experience troubled intimate partner relationships. In the
design process, the team addressed six fundamental questions related to the
several components of the IIM. Decisions made regarding the design of the
intervention based on the six questions are described. We focus in particular on
how the intervention is based on the Theory of Emerging Adulthood and the Theory
of Narrative Identity.
PMID- 28499572
TI - A National Survey on Nursing in Canadian ECT Departments.
PMID- 28499573
TI - Positive Thinking Training Intervention for Caregivers of Persons with Autism:
Establishing Fidelity.
AB - More than 3.5 million in the US are diagnosed with autism spectrum disorder (ASD)
and caregivers experience stress that adversely affects their well-being.
Positive thinking training (PTT) intervention can minimize that stress. However,
before testing the effectiveness of PTT, its fidelity must be established. This
pilot intervention trial examined fidelity of an online PTT intervention for ASD
caregivers with a random assignment of 73 caregivers to either the online PTT
intervention or to the control group. Quantitative data [Positive Thinking Skills
Scale (PTSS)] and qualitative data (online weekly homework) were collected. The
mean scores for the PTSS improved for the intervention group and decreased for
the control group post intervention. Evidence for use of PTT was found in
caregivers' online weekly homework. The findings provide evidence of the
implementation fidelity of PTT intervention and support moving forward to test
PTT effectiveness in promoting caregivers' well-being.
PMID- 28499574
TI - Use of Computer and Mobile Technologies in the Treatment of Depression.
AB - Major depression (MDD) is a common and disabling disorder. Research has shown
that most people with MDD receive either no treatment or inadequate treatment.
Computer and mobile technologies may offer solutions for the delivery of
therapies to untreated or inadequately treated individuals with MDD. The authors
review currently available technologies and research aimed at relieving symptoms
of MDD. These technologies include computer-assisted cognitive-behavior therapy
(CCBT), web-based self-help, Internet self-help support groups, mobile
psychotherapeutic interventions (i.e., mobile applications or apps), technology
enhanced exercise, and biosensing technology.
PMID- 28499575
TI - Childhood Enuresis: Current Diagnostic Formulations, Salient Findings, and
Effective Treatment Modalities.
AB - Enuresis constitutes a frequently encountered problem area for children that may
adversely affect social and emotional adjustment. This type of incontinence has
been of concern to the human family for centuries. A brief history of enuresis is
presented followed by current conceptualizations, diagnostic criteria, prevalence
rates and psychiatric comorbidities. Historic notions of causation together with
ineffective, sometimes barbaric treatments are then discussed, ending with a
presentation of evidence-based treatment modalities, with the urine alarm being
an essential element of effective treatment. An intervention termed dry bed
training combines the urine alarm with a series of procedures designed in part to
reduce relapse potential and should be a primary consideration for implementation
by treatment professionals. Finally, a brief case study is presented illustrating
special etiological and treatment considerations with juvenile psychiatric
patients.
PMID- 28499576
TI - An Introduction to the Model of Crisis Intervention Procedure for Borderline
Patients (CIP-BP): A Case Study.
AB - Borderline personality disorder is highly associated with suicidal behaviors. The
authors of the current case study present the introduction model of original
Crisis Intervention Procedure for Borderline Patients (CIP-BP) which is a method
focused on restoring emotional balance, reducing the severity of symptoms and the
risk of suicidal behavior, as well as developing optimum solutions for further
action. Its aim is to enable the patient to regain control of their emotional
memory, increase autonomy and restore important interpersonal relations by using
the original resources of this person. The procedure aims at providing nursing
personnel with a practical tool to effectively avert the crisis and prevent
further decompensation of BPD patients. Further pre-post study is required to
determine the effectiveness of the procedure.
PMID- 28499577
TI - Metabolic regulation of suppressive myeloid cells in cancer.
AB - Cancer cells rewire their metabolism to promote growth, survival, proliferation
and long-term maintenance. The common feature of this altered metabolism is the
increased glucose uptake and fermentation of glucose to lactate, which is
observed even in the presence of completely functioning mitochondria. This effect
is known as the 'Warburg Effect' and its intensive investigation in the last
decade has partially established either its causes or its functions. It is now
emerging that a major side effect of the Warburg Effect is immunosuppression,
which limits the immunogenicity of cancer cells and therefore restricts the
therapeutic efficacy of anticancer immunotherapy. Here we discuss how the
metabolic communication between cancer and infiltrating myeloid cells contributes
to cancer immune evasion and how the understanding of these mechanisms may
improve current immunotherapies.
PMID- 28499578
TI - Building a biomimetic membrane for neutron reflectivity investigation:
Complexity, asymmetry and contrast.
AB - The preparation and investigation of model membranes is deserving growing
interest both for the physics of complex systems, and for biology. The need of
simplified models should preserve mimicking the qualifying characteristics of
biological membranes, and keep non-invasive and detailed description. As a main
feature, biological membranes are non-homogeneous in the disposition of
components, both in the lateral and in the transverse direction. We prepared
asymmetric supported membranes containing GM1 ganglioside in biomimetic
proportion according to different protocols. Then, we studied their internal
structure by neutron reflectometry, providing few-Angstrom sensitivity in the
cross direction meanwhile avoiding radiation damage. This technique can also be
profitably applied to study interactions at the membrane surface. The best
protocol has proven to be the Langmuir-Blodgett/Langmuir-Schaefer depositions.
Notably, also the simpler and most accessible protocol of vesicle fusion was
found to be suitable for straightforward and good quality deposition of
compositionally asymmetric membranes.
PMID- 28499579
TI - Expression of recombinant truncated domains of mucus-binding (Mub) protein of
Lactobacillus plantarum in soluble and biologically active form.
PMID- 28499580
TI - Transient receptor potential (TRP) channels as molecular targets in lung
toxicology and associated diseases.
AB - The lungs as the gateways of our body to the external environment are essential
for gas exchange. They are also exposed to toxicants from two sides, the airways
and the vasculature. Apart from naturally produced toxic agents, millions of
human made chemicals were produced since the beginning of the industrial
revolution whose toxicity still needs to be determined. While the knowledge about
toxic substances is increasing only slowly, a paradigm shift regarding the
proposed mechanisms of toxicity at the plasma membrane emerged. According to
their broad-range chemical reactivity, the mechanism of lung injury evoked by
these agents has long been described as rather unspecific. Consequently,
therapeutic options are still restricted to symptomatic treatment. The
identification of molecular down-stream effectors in cells was a major step
forward in the mechanistic understanding of the action of toxic chemicals and
will pave the way for more causal and specific toxicity testing as well as
therapeutic options. In this context, the involvement of Transient Receptor
Potential (TRP) channels as chemosensors involved in the detection and effectors
of toxicant action is an attractive concept intensively discussed in the
scientific community. In this review we will summarize recent evidence for an
involvement of TRP channels (TRPA1, TRPC4, TRPC6, TRPV1, TRPV4, TRPM2 and TRPM8)
expressed in the lung in pathways of toxin sensing and as mediators of lung
inflammation and associated diseases like asthma, COPD, lung fibrosis and edema
formation. Specific modulators of these channels may offer new therapeutic
options in the future and will endorse strategies for a causal, specifically
tailored treatment based on the mechanistic understanding of molecular events
induced by lung-toxic agents.
PMID- 28499581
TI - Defining "mental disorder" in legal contexts.
PMID- 28499582
TI - Corrigendum to "Interplay between microbial trait dynamics and population
dynamics revealed by the combination of laboratory experiment and computational
approaches" [Journal of Theoretical Biology 419 (2017) 201-210].
PMID- 28499584
TI - Extremely high sulfate reduction, sediment oxygen demand and benthic nutrient
flux associated with a large-scale artificial dyke and its implication to benthic
pelagic coupling in the Yeongsan River estuary, Yellow Sea.
AB - We investigated environmental impact of large-scale dyke on the sediment
geochemistry, sulfate reduction rates (SRRs), sediment oxygen demand (SOD) and
potential contribution of benthic nutrient flux (BNF) to primary production in
the Yeongsan River estuary, Yellow Sea. The sediment near the dyke (YE1) with
high organic carbon (Corg) content (>4%, dry wt.) was characterized by extremely
high SOD (327mmolm-2d-1) and SRRs (91-140mmolm-2d-1). The sulfate reduction
accounted for 73% of Corg oxidation, and was responsible for strikingly high
concentrations of NH4+ (7.7mM), PO43- (67MUM) and HS- (487MUM) in pore water. The
BNF at YE1 accounted for approximately 200% of N and P required for primary
production in the water column. The results present one of the most extreme cases
that the construction of an artificial dyke may have profound impacts on the
biogeochemical and ecological processes in coastal ecosystems.
PMID- 28499583
TI - Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in
patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international,
open-label, randomised, controlled, phase 3, multicentre trial.
AB - BACKGROUND: Previous trials from our group suggested an overall survival benefit
with five cycles of adjuvant full-dose epirubicin plus ifosfamide in localised
high-risk soft-tissue sarcoma of the extremities or trunk wall, and no difference
in overall survival benefit between three cycles versus five cycles of the same
neoadjuvant regimen. We aimed to show the superiority of the neoadjuvant
administration of histotype-tailored regimen to standard chemotherapy. METHODS:
For this international, open-label, randomised, controlled, phase 3, multicentre
trial, patients were enrolled from 32 hospitals in Italy, Spain, France, and
Poland. Eligible patients were aged 18 years or older with localised, high-risk
(high malignancy grade, 5 cm or longer in diameter, and deeply located according
to the investing fascia), soft-tissue sarcoma of the extremities or trunk wall
and belonging to one of five histological subtypes: high-grade myxoid
liposarcoma, leiomyosarcoma, synovial sarcoma, malignant peripheral nerve sheath
tumour, and undifferentiated pleomorphic sarcoma. Patients were randomly assigned
(1:1) to receive three cycles of full-dose standard chemotherapy (epirubicin 60
mg/m2 per day [short infusion, days 1 and 2] plus ifosfamide 3 g/m2 per day [days
1, 2, and 3], repeated every 21 days) or histotype-tailored chemotherapy: for
high-grade myxoid liposarcoma, trabectedin 1.3 mg/m2 via 24-h continuous
infusion, repeated every 21 days; for leiomyosarcoma, gemcitabine 1800 mg/m2 on
day 1 intravenously over 180 min plus dacarbazine 500 mg/m2 on day 1
intravenously over 20 min, repeated every 14 days; for synovial sarcoma, high
dose ifosfamide 14 g/m2, given over 14 days via an external infusion pump, every
28 days; for malignant peripheral nerve sheath tumour, intravenous etoposide 150
mg/m2 per day (days 1, 2, and 3) plus intravenous ifosfamide 3 g/m2 per day (days
1, 2, and 3), repeated every 21 days; and for undifferentiated pleomorphic
sarcoma, gemcitabine 900 mg/m2 on days 1 and 8 intravenously over 90 min plus
docetaxel 75 mg/m2 on day 8 intravenously over 1 h, repeated every 21 days.
Randomisation was stratified by administration of preoperative radiotherapy and
by country of enrolment. Computer-generated random lists were prepared by use of
permuted balanced blocks of size 4 and 6 in random sequence. An internet-based
randomisation system ensured concealment of the treatment assignment until the
patient had been registered into the system. No masking of treatment assignments
was done. The primary endpoint was disease-free survival. The primary and safety
analyses were planned in the intention-to-treat population. We did yearly
futility analyses on an intention-to-treat basis. The study was registered with
ClinicalTrials.gov, number NCT01710176, and with the European Union Drug
Regulating Authorities Clinical Trials, number EUDRACT 2010-023484-17, and is
closed to patient entry. FINDINGS: Between May 19, 2011, and May 13, 2016, 287
patients were randomly assigned to a group (145 to standard chemotherapy and 142
to histotype-tailored chemotherapy), all of whom, except one patient assigned to
standard chemotherapy, were included in the efficacy analysis (97 [34%] with
undifferentiated pleomorphic sarcoma; 64 [22%] with high-grade myxoid
liposarcoma; 70 [24%] with synovial sarcoma; 27 [9%] with malignant peripheral
nerve sheath tumour; and 28 [10%] with leiomyosarcoma). At the third futility
analysis, with a median follow-up of 12.3 months (IQR 2.75-28.20), the projected
disease-free survival at 46 months was 62% (95% CI 48-77) in the standard
chemotherapy group and 38% (22-55) in the histotype-tailored chemotherapy group
(stratified log-rank p=0.004; hazard ratio 2.00, 95% CI 1.22-3.26; p=0.006). The
most common grade 3 or higher adverse events in the standard chemotherapy group
(n=125) were neutropenia (107 [86%]), anaemia (24 [19%]), and thrombocytopenia
(21 [17%]); the most common grade 3 or higher adverse event in the histotype
tailored chemotherapy group (n=114) was neutropenia (30 [26%]). No treatment
related deaths were reported in both groups. In agreement with the Independent
Data Monitoring Committee, the study was closed to patient entry after the third
futility analysis. INTERPRETATION: In a population of patients with high-risk
soft-tissue sarcoma, we did not show any benefit of a neoadjuvant histotype
tailored chemotherapy regimen over the standard chemotherapy regimen. The benefit
seen with the standard chemotherapy regimen suggests that this benefit might be
the added value of neoadjuvant chemotherapy itself in patients with high-risk
soft-tissue sarcoma. FUNDING: European Union grant (Eurosarc FP7 278472).
PMID- 28499586
TI - [Gemcitabine-induced thrombotic microangiopathy: Can we improve screening and
treatment?]
AB - Thrombotic microangiopathy is a rare but severe complication of treatment with
gemcitabine. Its prevalence increases because gemcitabine's indications are
growing. We report four cases, which presented with common clinical and
biological manifestations, i.e. high blood pressure, proteinuria and increasing
plasmatic creatinine level. However, severity was not similar, hemodialysis was
inconstant. There is no consensus on treatment for this condition. Stopping
gemcitabine is essential. Treatment was dispensed considering the severity of the
presentation: plasma exchange therapy of variable outcome, and eculizumab, which
was efficient when used. It's important to note that this syndrome includes
common and frequent signs in patients receiving chemotherapies. But they must
encourage the research of most specific signs, such as hypertension, mechanic
hemolysis signs, proteinuria or hematuria, in order to recognize thrombotic
microangiopathy as early as possible to treat it precociously, and to prevent
additional gemcitabine injections.
PMID- 28499585
TI - Multipotent adult progenitor cells improve the hematopoietic function in
myelodysplasia.
AB - BACKGROUND AIMS: Myelodysplastic syndromes (MDS) are a group of clonal stem cell
disorders affecting the normal hematopoietic differentiation process and leading
to abnormal maturation and differentiation of all blood cell lineages. Treatment
options are limited, and there is an unmet medical need for effective therapies
for patients with severe cytopenias. METHODS: We demonstrate that multipotent
adult progenitor cells (MAPC) improve the function of hematopoietic progenitors
derived from human MDS bone marrow (BM) by significantly increasing the frequency
of primitive progenitors as well as the number of myeloid colonies. RESULTS: This
effect was more pronounced in a non-contact culture, indicating the importance of
soluble factors produced by the MAPC cells. Moreover, the cells did not stimulate
the growth of the abnormal MDS clone, as shown by fluorescent in situ
hybridization analysis on BM cells from patients with a known genetic
abnormality. We also demonstrate that MAPC cells can provide stromal support for
patient-derived hematopoietic cells. When MAPC cells were intravenously injected
into a mouse model of MDS, they migrated to the site of injury and increased the
hematopoietic function in diseased mice. DISCUSSION: The preclinical studies
undertaken here indicate an initial proof of concept for the use of MAPC cell
therapy in patients with MDS-related severe and symptomatic cytopenias and should
pave the way for further investigation in clinical trials.
PMID- 28499588
TI - Clinical and molecular characterization of a 13-year-old Indian boy with cutis
laxa type 2B: Identification of two novel PYCR1 mutations by amplicon-based
semiconductor exome sequencing.
PMID- 28499587
TI - The phosphodiesterase 4 inhibitor apremilast inhibits Th1 but promotes Th17
responses induced by 6-sulfo LacNAc (slan) dendritic cells.
AB - BACKGROUND: The phosphodiesterase 4 (PDE4) inhibitor apremilast increases
cellular cAMP levels and has proven effective in the treatment of psoriasis and
psoriasis arthritis. We recently described 6-sulfo LacNAc dendritic cells
(slanDCs) as immature DCs in blood and as a subset of inflammatory dermal DCs in
psoriasis with a pronounced capacity to produce proinflammatory cytokines and to
program Th17/Th1 T cell responses. OBJECTIVE: The aim of this study was to
investigate possible immune regulatory effects of the PDE4 inhibitor apremilast
on slanDCs. METHODS: In vitro studies were performed analyzing the effects of
apremilast on the proinflammatory function of slanDCs and their capacity to
induce Th1/Th17-biased T cell responses. RESULTS: Increasing cAMP levels in
slanDCs by PDE4 inhibition strongly reduced production of IL-12 and TNF-alpha. In
line with these findings, co-culture experiments with apremilast-pulsed slanDCs
and allogeneic T cells either from psoriasis patients or healthy controls,
revealed a significant reduction of IFN-gamma production and expression of the
transcription factor T-bet. In parallel, production of IL-23 and IL-1beta by
slanDCs was increased and co-cultured T cells revealed a largely augmented IL-17
production and an upregulated RORyt expression. CONCLUSIONS: We here demonstrate
anti-inflammatory as well as Th17-promoting effects of apremilast when studying
blood precursors of human inflammatory dermal dendritic cells. In the concert of
the broad anti-inflammatory effects of apremilast on keratinocytes, fibroblasts
and endothelial cells, the dual effect on slan+ inflammatory dermal DCs should be
taken into account and may constrain therapeutic responses.
PMID- 28499589
TI - Askin's Tumor. A Rare Diagnosis in an Elderly Patient.
PMID- 28499590
TI - MiR-93-5p inhibits the EMT of breast cancer cells via targeting MKL-1 and STAT3.
AB - Epithelial-mesenchymal transition (EMT) plays an important role in breast cancer
cell metastasis. Both (megakaryoblastic leukemia)/myocardin-like 1 (MKL-1) and
Signal transducer and activator of transcription 3 (STAT3) have been implicated
in the control of cellular metabolism, survival and growth. Our previous study
has shown that cooperativity of MKL-1 and STAT3 promoted breast cancer cell
migration. Herein, we demonstrate a requirement for MKL-1 and STAT3 in miRNA
mediated cellular EMT to affect breast cancer cell migration. Here we show that
cooperativity of MKL-1 and STAT3 promoted the EMT of MCF-7 cells. Importantly,
MKL-1 and STAT3 promoted the expression of Vimentin via its promoter CArG box.
Interestingly, miR-93-5p inhibits the EMT of breast cancer cells through
suppressing the expression of MKL-1 and STAT3 via targeted their 3'UTR. These
results demonstrated a novel pathway through which miR-93-5p regulates MKL-1 and
STAT3 to affect EMT controlling breast cancer cell migration.
PMID- 28499591
TI - Chronic exposure to dim artificial light at night decreases fecundity and adult
survival in Drosophila melanogaster.
AB - The presence of artificial light at night is expanding in geographical range and
increasing in intensity to such an extent that species living in urban
environments may never experience natural darkness. The negative ecological
consequences of artificial night lighting have been identified in several key
life history traits across multiple taxa (albeit with a strong vertebrate focus);
comparable data for invertebrates is lacking. In this study, we explored the
effect of chronic exposure to different night-time lighting intensities on
growth, reproduction and survival in Drosophila melanogaster. We reared three
generations of flies under identical daytime light conditions (2600lx) and one of
four ecologically relevant ALAN treatments (0, 1, 10 or 100lx), then explored
variation in oviposition, number of eggs produced, juvenile growth and survival
and adult survival. We found that, in the presence of light at night (1, 10 and
100lx treatments), the probability of a female commencing oviposition and the
number of eggs laid was significantly reduced. This did not translate into
differences at the juvenile phase: juvenile development times and the probability
of eclosing as an adult were comparable across all treatments. However, we
demonstrate for the first time a direct link between chronic exposure to light at
night (greater than 1lx) and adult survival. Our data highlight that ALAN has the
capacity to cause dramatic shifts in multiple life history traits at both the
individual and population level. Such shifts are likely to be species-specific,
however a more in depth understanding of the broad-scale impact of ALAN and the
relevant mechanisms driving biological change is urgently required as we move
into an increasing brightly lit future.
PMID- 28499592
TI - Risk factors for poor outcomes of children with acute acalculous cholecystitis.
AB - BACKGROUND: Acute acalculous cholecystitis (AAC) is generally considered to be a
mild disease in children; however, if left untreated or treated without caution,
AAC can lead to severe outcomes, such as death. The objectives of this study were
to present the clinical features and identify the predictors of mortality in
pediatric AAC. METHODS: Patients diagnosed with AAC between 2005 and 2012 were
enrolled. AAC was defined by the presence of fever and an echo-proven thickened
gallbladder wall exceeding 4 mm. A poor health outcome was defined as death.
Further information related to the demographics, clinical manifestations,
laboratory results, ultrasound findings, and pathogens present in the AAC
patients was also collected. Predictors of mortality were identified by
association analyses and confirmed by multivariate logistic regression. RESULTS:
A total of 147 pediatric AAC patients (male/female = 1.01, mean age = 5.2 years)
were included in this retrospective study. The most common clinical presentation
was an elevated C-reactive protein level (84%) followed by hepatomegaly (80%) and
anorexia (78%). AAC in children was associated with various diseases, including
infectious diseases (70%), systemic diseases (13%), and malignancy (11%).
Fourteen of the 147 (9.25%) patients died during the study period. The presences
of thrombocytopenia, anemia, gallbladder sludge, hepatitis, and/or sepsis plus
hepatitis were found to be the important predictors of AAC mortality.
CONCLUSIONS: The factors associated with AAC mortality were anemia,
thrombocytopenia, gallbladder sludge, hepatitis, and sepsis plus hepatitis. These
predictors are likely to help clinicians identify patients who are at a high risk
of poor prognoses and make appropriate clinical decisions.
PMID- 28499593
TI - Expanding surgical skills and knowledge after training: Lifelong learning puts
patients first.
PMID- 28499594
TI - The value of salvage surgery after stereotactic body radiotherapy failure: A
sticky conundrum.
PMID- 28499595
TI - Impact of Calcium on Chronic Total Occlusion Percutaneous Coronary Interventions.
AB - We sought to examine the impact of calcific deposits on the outcomes of chronic
total occlusion (CTO) percutaneous coronary intervention (PCI). The outcomes of
1,476 consecutive CTO PCIs performed in 1,453 patients (65.5 +/- 10 years, 85%
male) between 2012 and 2016 at 11 US centers were evaluated. Moderate or severe
quantity of calcium was present in 58% of target lesions. Calcified lesions were
more tortuous and more likely to have proximal cap ambiguity and interventional
collaterals. PCI of moderately/severely calcified CTOs more often required use of
the retrograde approach (54% vs 30%, p <0.001) and was associated with longer
procedure and fluoroscopy time and higher air kerma radiation dose and contrast
volume. Moderate/severe quantity of calcium was associated with lower technical
(86.6% vs 93.8%, p <0.001) and procedural (84.4% vs 92.7%, p <0.001) success
rates and higher incidence of major adverse cardiac events (3.7% vs 1.8%, p =
0.033). On multivariate analysis, the presence of moderate/severe quantity of
calcium was not independently associated with technical success. Balloon
angioplasty was the most common lesion preparation technique for calcified
lesions, followed by rotational atherectomy and laser. To conclude, in a
contemporary, multicenter registry, moderate/severe calcific deposits were
present in 58% of attempted CTO lesions and were associated with higher use of
the retrograde approach, lower success, and higher complication rates. However,
on multivariable analysis, the amount of calcium was not independently associated
with technical success.
PMID- 28499596
TI - Magnetic porous beta-cyclodextrin polymer for magnetic solid-phase extraction of
microcystins from environmental water samples.
AB - Microcystins (MCs) are cyclic heptapeptide toxins and tumor promoters produced by
cyanobacteria, which threaten the health of humans. In this study, magnetic
porous beta-cyclodextrin polymer (Fe3O4@SiO2@P-CDP) was synthesized and
characterized by transmission electron microscopy, scanning electron microscopy,
energy dispersive X-ray spectrometry, Fourier transform infrared spectrometry, X
ray diffraction, nitrogen adsorption porosimetry and vibrating sample
magnetometer. The synthesized Fe3O4@SiO2@P-CDP particles were then used for
magnetic solid-phase extraction (MSPE) of MCs from environmental water samples,
and exhibited excellent extraction performance, especially for MC-RR. Coupled
with high-performance liquid chromatography with tandem mass spectrometry (HPLC
MS/MS), a simple, efficient and sensitive method for determination of trace
levels of MCs was established. After the optimization of conditions, wide linear
ranges (2.0-1000pgmL-1), good linearity (r2>=0.9996) and acceptable repeatability
(RSD<=9.4%, n=5) were obtained. The limits of detection (LODs, S/N=3) and limits
of quantification (LOQs, S/N=10) for three MCs (MC-LR, MC-RR and MC-YR) were in
the range of 1.0-2.0pgmL-1 and 2.0-5.0pgmL-1, respectively. Typical water samples
were analyzed by the developed method, and trace levels of MC-LR and MC-RR were
detected. The results demonstrate that the developed method has great potential
for the determination of MCs in complicated matrix.
PMID- 28499597
TI - Effect of cationic monomer content on polyacrylamide copolymers by frit-inlet
asymmetrical flow field-flow fractionation/multi-angle light scattering.
AB - In this study, ultrahigh-molecular-weight (MW) (>107Da) cationic polyacrylamides
(C-PAMs), which are water-soluble polymers used in waste water treatment, were
characterized using frit-inlet asymmetrical flow field-flow fractionation coupled
with multi-angle light scattering and differential refractive detection. C-PAMs
copolymerized with acryloxyethyltrimethyl ammonium chloride (DAC) were prepared
by varying the feed amount of cationic monomer, polymerization method (solution
vs. emulsion), and degree of branching. The MW of the copolymers prepared using
emulsion polymerization (107-109Da) was generally larger than that of copolymers
prepared using solution polymerization (4*107-108Da). When the amount of cationic
monomer was increased from 10 to 55mol% in solution polymerization, hydrophobic
contraction of the core induced formation of more compact C-PAMs. The copolymers
prepared using emulsion polymerization formed highly aggregated or supercoil
structures owing to increased intermolecular hydrophobic interaction when less
cationic monomer was used. However, the MW decreased with increased cationic
group content. In addition, C-PAMs larger than ~108Da prepared using the emulsion
method were separated by steric/hyperlayer elution mode while those in the 107
108Da range were analyzed in either normal or steric/hyperlayer mode depending on
the decay patterns of field programming. Moreover, branched copolymers were found
to be resolved with different elution modes under the same field decay pattern
depending on the degree of branching: steric/hyperlayer for low-branching and
normal for high-branching C-PAMs.
PMID- 28499598
TI - Simultaneous electromembrane extraction of cationic and anionic herbicides across
hollow polymer inclusion membranes with a bubbleless electrode.
AB - A new electric-field driven extraction approach based on the integration of a
bubbleless electrode into the electromembrane extraction (EME) across hollow
polymer inclusion membranes (HPIMs) was demonstrated for the first time. The
bubbleless electrode was prepared based on an in-situ synthesised polyacrylamide
within a fused silica capillary. The electrode functions as a salt bridge, which
conducts the electrical current between the acceptor phase in the lumen of the
HPIM and the acceptor solution in the reservoir connected to a high voltage
supply through a platinum electrode. Two types of HPIMs were employed, which
consisted of desired proportions of cellulose acetate as base polymer, tris(2
ethylhexyl)phosphate as plasticizer, and di-(2-ethylhexyl)phosphoric acid as
anionic carrier or Aliquat 336 as cationic carrier, respectively. The EME
strategy was evaluated for the simultaneous determination of cationic quaternary
ammonium and anionic chlorophenoxy acetic acid herbicides present in the river
water, respectively. The analysis was carried out using capillary electrophoresis
coupled with UV and contactless conductivity detection. Under the optimised
conditions, enrichment factors in the range of 152-185-fold were obtained from
4mL of river water sample with a 20min extraction time and an applied voltage of
3000V. The proposed method provided good linearity with correlation coefficients
ranging from 0.9982 to 0.9997 over a concentration range of 1-1000MUg/L. The
detection limits of the method for the herbicides were in the range of 0.3
0.4MUg/L, with relative standard deviations of between 4.8% and 8.5%. The
relative recoveries obtained when analysing the spiked river water ranged from
99.1% to 100%. A comparison was also made between the newly developed approach
with the conventional EME setup by placing the platinum electrode directly in the
lumen of the HPIMs.
PMID- 28499599
TI - Gas chromatography - mass spectrometry data processing made easy.
AB - Evaluation of GC-MS data may be challenging due to the high complexity of data
including overlapped, embedded, retention time shifted and low S/N ratio peaks.
In this work, we demonstrate a new approach, PARAFAC2 based Deconvolution and
Identification System (PARADISe), for processing raw GC-MS data. PARADISe is a
computer platform independent freely available software incorporating a number of
newly developed algorithms in a coherent framework. It offers a solution for
analysts dealing with complex chromatographic data. It allows extraction of
chemical/metabolite information directly from the raw data. Using PARADISe
requires only few inputs from the analyst to process GC-MS data and subsequently
converts raw netCDF data files into a compiled peak table. Furthermore, the
method is generally robust towards minor variations in the input parameters. The
method automatically performs peak identification based on deconvoluted mass
spectra using integrated NIST search engine and generates an identification
report. In this paper, we compare PARADISe with AMDIS and ChromaTOF in terms of
peak quantification and show that PARADISe is more robust to user-defined
settings and that these are easier (and much fewer) to set. PARADISe is based on
non-proprietary scientifically evaluated approaches and we here show that
PARADISe can handle more overlapping signals, lower signal-to-noise peaks and do
so in a manner that requires only about an hours worth of work regardless of the
number of samples. We also show that there are no non-detects in PARADISe,
meaning that all compounds are detected in all samples.
PMID- 28499600
TI - Lipid vesicles in pulsed electric fields: Fundamental principles of the membrane
response and its biomedical applications.
AB - The present review focuses on the effects of pulsed electric fields on lipid
vesicles ranging from giant unilamellar vesicles (GUVs) to small unilamellar
vesicles (SUVs), from both fundamental and applicative perspectives. Lipid
vesicles are the most popular model membrane systems for studying biophysical and
biological processes in living cells. Furthermore, as vesicles are made from
biocompatible and biodegradable materials, they provide a strategy to create safe
and functionalized drug delivery systems in health-care applications. Exposure of
lipid vesicles to pulsed electric fields is a common physical method to
transiently increase the permeability of the lipid membrane. This method, termed
electroporation, has shown many advantages for delivering exogenous molecules
including drugs and genetic material into vesicles and living cells. In addition,
electroporation can be applied to induce fusion between vesicles and/or cells.
First, we discuss in detail how research on cell-size GUVs as model cell systems
has provided novel insight into the basic mechanisms of cell electroporation and
associated phenomena. Afterwards, we continue with a thorough overview how
electroporation and electrofusion have been used as versatile methods to
manipulate vesicles of all sizes in different biomedical applications. We
conclude by summarizing the open questions in the field of electroporation and
possible future directions for vesicles in the biomedical field.
PMID- 28499601
TI - Multicomponent nanocrystals with anti-Stokes luminescence as contrast agents for
modern imaging techniques.
AB - Lanthanide-doped upconversion nanoparticles (UCNPs) have recently attracted great
attention in theranostics due to their exceptional optical and physicochemical
properties, which enable the design of a novel UCNP-based nanoplatform for
luminescent imaging, temperature mapping, sensing, and therapy. In addition,
UCNPs are considered to be ideal building blocks for development of multimodal
probes for cells and whole body imaging, exploiting simple variation of host
matrix, dopant ions, and surface chemistry. Modalities responsible for magnetic
resonance imaging (MRI), computed tomography (CT), and positron emission
tomography (PET)/single-photon emission computed tomography (SPECT) are embedded
in a single UC nanocrystal, providing integrating effect over any modality alone
in terms of the efficiency and sensitivity for clinical innovative diagnosis
through multimodal bioimaging. In particular, we demonstrate applications of
UCNPs as a new nanoplatform for optical and multimodal cancer imaging in vitro
and in vivo and extend discussions to delivery of UCNP-based therapeutic agents
for photodynamic and photothermal cancer treatments.
PMID- 28499602
TI - From polyelectrolyte complexes to polyelectrolyte multilayers: Electrostatic
assembly, nanostructure, dynamics, and functional properties.
AB - Polyelectrolyte complexes (PECs) are three-dimensional macromolecular structures
formed by association of oppositely charged polyelectrolytes in solution.
Polyelectrolyte multilayers (PEMs) can be considered a special case of PECs
prepared by layer-by-layer (LbL) assembly that involves sequential deposition of
molecular-thick polyelectrolyte layers with nanoscale control over the size,
shape, composition and internal organization. Although many functional PEMs with
novel physical and chemical characteristics have been developed, the current
practical applications of PEMs are limited to those that require only a few
bilayers and are relatively easy to prepare. The viability of such engineered
materials can be realized only after overcoming the scientific and engineering
challenges of understanding the kinetics and transport phenomena involved in the
multilayer growth and the factors governing their final structure, composition,
and response to external stimuli. There is a great need to model PEMs and to
connect PEM behavior with the characteristics of the PEC counterparts to allow
for prediction of performance and better design of multilayered materials. This
review focuses on the relationship between PEMs and PECs. The constitutive
interactions, the thermodynamics and kinetics of polyelectrolyte complexation and
PEM formation, PEC phase behavior, PEM growth, the internal structure and
stability in PEMs and PECs, and their response to external stimuli are presented.
Knowledge of such interactions and behavior can guide rapid fabrication of PEMs
and can aid their applications as nanocomposites, coatings, nano-sized reactors,
capsules, drug delivery systems, and in electrochemical and sensing devices. The
challenges and opportunities in future research directions are also discussed.
PMID- 28499603
TI - Bio-templated silica composites for next-generation biomedical applications.
AB - Silica-based materials have extensive biomedical applications owing to their
unique physical, chemical, and biological properties. Recently, increasing
studies have examined the mechanisms involved in biosilicification to develop
novel, fine-tunable, eco-friendly materials and/or technologies. In this review,
we focus on recent developments in bio-templated silica synthesis and relevant
applications in drug delivery systems, tissue engineering, and biosensing.
PMID- 28499604
TI - Iron oxide nanoparticles - In vivo/in vitro biomedical applications and in silico
studies.
AB - The review presents a broad overview of the biomedical applications of surface
functionalized iron oxide nanoparticles (IONPs) as magnetic resonance imaging
(MRI) agents for sensitive and precise diagnosis tool and synergistic combination
with other imaging modalities. Then, the recent progress in therapeutic
applications, such as hyperthermia is discussed and the available toxicity data
of magnetic nanoparticles concerning in vitro and in vivo biomedical applications
are addressed. This review also presents the available computer models using
molecular dynamics (MD), Monte Carlo (MC) and density functional theory (DFT), as
a basis for a complete understanding of the behaviour and morphology of
functionalized IONPs, for improving NPs surface design and expanding the
potential applications in nanomedicine.
PMID- 28499605
TI - Interfacial characteristics of binary polymer blend films spread at the air-water
interface.
AB - The interfacial characteristics of binary polymer blend films spread at the air
water interface are reviewed, focusing on their surface pressures, interfacial
structures, and dilational moduli as a function of the miscibility. Miscible
polymer blend films show thermodynamic, structural, and dynamic properties which
are a combination of those from both components in the polymer blend present at
the air-water interface. No preferential adsorption is observed and the behavior
does not depend on the surface concentration regime. In contrast, for immiscible
polymer blend films, preferential adsorption of one polymer phase occurs at the
air-water interface and the interfacial characteristics in the semi-dilute and
concentrated regimes are strongly controlled by one of the components of the
adsorbed polymer.
PMID- 28499606
TI - Finite element analysis of stress extent at peri-implant bone surrounding
external hexagon or Morse taper implants.
AB - PURPOSE: The purpose of the present study was to evaluate the distribution of
stresses and consequent bone volume affected surrounding external hexagon or
Morse taper dental implant systems by finite element analysis. MATERIAL AND
METHODS: Two different dental implant-abutment designs were assessed: external
hexagon or Morse taper joints. A mandibular bone model obtained from a computed
tomography scan was used. The implant-abutment systems were axially or obliquely
(45 degrees ) loaded on 150 N relatively to the central axis of the implant. The
von Mises stresses were analysed in terms of magnitude and volume of affected
surrounding bone. RESULTS: The von Mises equivalent values found on the cortical
bone were higher than that recorded on the trabecular bone. Additionally, the
bone volume associated with high stress values was higher in cortical and
trabecular bone for oblique loading compared to axial loading. The values of von
Mises equivalent stress around Morse taper implant-abutment system were lower on
both axial and oblique loads than those recorded for external hexagon implant
abutment systems. CONCLUSIONS: Morse taper implant joints revealed a proper
biomechanical behavior when compared to external hexagon systems concerning a
significant volume of surrounding peri-implant bone subjected to lower stresses
values.
PMID- 28499608
TI - Fat or fit: The big oxymoron of (metabolically) healthy obesity.
PMID- 28499607
TI - Evaluation of intensity modulated radiation therapy dose painting for localized
prostate cancer using 68Ga-HBED-CC PSMA-PET/CT: A planning study based on
histopathology reference.
AB - PURPOSE: To demonstrate the feasibility and to evaluate the tumour control
probability (TCP) and normal tissue complication probability (NTCP) of IMRT dose
painting using 68Ga-HBED-CC PSMA PET/CT for target delineation in prostate cancer
(PCa). METHODS AND MATERIALS: 10 patients had PSMA PET/CT scans prior to
prostatectomy. GTV-PET was generated on the basis of an intraprostatic SUVmax of
30%. Two IMRT plans were generated for each patient: Plan77 which consisted of
whole-prostate IMRT to 77Gy, and Plan95 which consisted of whole-prostate IMRT to
77Gy and a simultaneous integrated boost to the GTV-PET up to 95Gy (35
fractions). The feasibility of these plans was judged by their ability to adhere
to the FLAME trial protocol. TCP-histo/-PET were calculated on co-registered
histology (GTV-histo) and GTV-PET, respectively. NTCPs for rectum and bladder
were calculated. RESULTS: All plans reached prescription doses whilst adhering to
dose constraints. In Plan77 and Plan95 mean doses in GTV-histo were 75.8+/-0.3Gy
and 96.9+/-1Gy, respectively. Average TCP-histo values for Plan77 and Plan95 were
70% (range: 15-97%), and 96% (range: 78-100%, p<0.0001). Average TCP-PET values
for Plan77 and Plan95 were 55% (range: 27-82%), and 100% (range: 99-100%,
p<0.0001). There was no significant difference between TCP-PET and TCP-histo in
Plan95 (p=0.25). There were no significant differences in rectal (p=0.563) and
bladder (p=0.3) NTCPs. CONCLUSIONS: IMRT dose painting using PSMA PET/CT was
technically feasible and resulted in significantly higher TCPs without higher
NTCPs.
PMID- 28499609
TI - Achilles tendon xanthomas are associated with the presence and burden of
subclinical coronary atherosclerosis in heterozygous familial
hypercholesterolemia: A pilot study.
AB - BACKGROUND AND AIMS: Achilles tendon xanthomas (ATX) are a sign of long-term
exposure to high blood cholesterol in familial hypercholesterolemia (FH)
patients, which have been associated with cardiovascular disease. We evaluated
the ATX association with the presence and extent of subclinical coronary
atherosclerosis in heterozygous FH patients. METHODS: 102 FH patients diagnosed
by US-MEDPED criteria (67% with genetically proven FH), with median LDL-C 279
mg/dL (interquartile range: 240; 313), asymptomatic for cardiovascular disease,
underwent computed tomography angiography and coronary artery calcium (CAC)
quantification. Subclinical coronary atherosclerosis was quantified by CAC,
segment-stenosis (SSS) and segment-involvement (SIS) scores. Adjusted Poisson
regression was used to assess the association of ATX with subclinical
atherosclerosis burden as continuous variables. RESULTS: Patients with ATX (n =
21, 21%) had higher LDL-C and lipoprotein(a) [Lp(a)] concentrations as well as
greater CAC scores, SIS and SSS (p < 0.05). After adjusting for age, sex,
smoking, hypertension, previous statin use, HDL-C, LDL-C and Lp(a)
concentrations, there was an independent positive association of ATX presence
with CAC scores (beta = 1.017, p < 0.001), SSS (beta = 0.809, p < 0.001) and SIS
(beta = 0.640, p < 0.001). CONCLUSIONS: ATX are independently associated with the
extension of subclinical coronary atherosclerosis quantified by tomographic
scores in FH patients.
PMID- 28499610
TI - Effects of cyanobacteria Oscillatoria sp. lipopolysaccharide on B cell activation
and Toll-like receptor 4 signaling.
AB - Cyanobacteria ("blue-green algae"), such as Oscillatoria sp., are a ubiquitous
group of bacteria found in freshwater systems worldwide that are linked to
illness and in some cases, death among humans and animals. Exposure to
cyanobacteria occurs via ingestion of contaminated water or food-products.
Exposure of the gut to these bacteria also exposes their toxins, such as
lipopolysaccharide (LPS), to B cells in the gut associated lymphoid tissue.
However, the effect of Oscillatoria sp. LPS on B cell activation is unknown. To
test the hypothesis that Oscillatoria sp. LPS exposure to murine B cells would
result in B cell activation, murine B cells were incubated in the absence or
presence of Oscillatoria sp. LPS or E. coli LPS as a positive control. The data
indicate that Oscillatoria sp. LPS induces B cells to proliferate, upregulate MHC
II and CD86, enhance antigen uptake and induce IgM production at low levels.
Additional studies demonstrate that this low level of stimulation may be due to
incomplete TLR4 signaling induced by Oscillatoria sp. LPS, since IRF-3 is not
induced in B cells after stimulation with Oscillatoria sp. LPS. These findings
have important implications for the mechanisms of toxicity of cyanobacteria in
both humans and animals.
PMID- 28499611
TI - Silver nanoparticle-induced phosphorylation of histone H3 at serine 10 is due to
dynamic changes in actin filaments and the activation of Aurora kinases.
AB - The phosphorylation of histone H3 at serine 10 (p-H3S10) has been closely
correlated with mitotic chromosome condensation. We previously reported that
silver nanoparticles (AgNPs) significantly induced p-H3S10 independent of
mitosis. In the present study, we examined the mechanisms underlying the
induction of p-H3S10 by AgNPs. A treatment with AgNPs markedly induced p-H3S10 in
a dose-dependent manner in three types of cell lines, and this was dependent on
the cellular incorporation of AgNPs. The immunofluorescent staining of AgNP
induced p-H3S10 was thin and solid throughout the nucleus, and differed from that
normally associated with mitosis. AgNPs induced the formation of globular actin
in a dose-dependent manner. Latrunculin B (LatB) and phalloidin, inhibitors of
actin polymerization and depolymerization, respectively, inhibited p-H3S10,
suggesting that dynamic changes in actin filaments are related to AgNP-induced p
H3S10. Furthermore, p-H3S10 was mediated by Aurora kinase (AURK) pathways, which
were suppressed by LatB and siRNA for cofilin 1, an actin-depolymerizing protein.
AgNO3 (Ag ions) exerted similar effects to those of AgNPs. These results suggest
that Ag ions released from AgNPs incorporated into inner cells changed the
dynamics of actin filaments, and this was followed by the activation of AURKs,
leading to the induction of p-H3S10.
PMID- 28499612
TI - Environmentally relevant dose of arsenic interferes in functions of human
monocytes derived dendritic cells.
AB - Arsenic is a major environmental pollutant and highly hazardous toxin to human
health, which well established as carcinogen and immune deregulatory properties.
Dendritic cells (DCs) have a pivotal role in cell-mediated immunity for T-cell
activation and antigen presentation. In this study, T cell activation, some key
functional genes expression, cell stability and phagocytosis capacity of human
monocytes derived DCs (MDDCs) were analyzed after in vitro exposure to very low
dose of arsenic for 12 and 24h. Arsenic decreased continually phagocytosis
capacity of MDDCs. Furthermore, down-regulation of the cell-surface expression of
the co-stimulatory molecule CD40 after 24h post treatment with arsenic, confirmed
arsenic interferers in the phagocytosis process. Pro inflammatory cytokines,
IL1beta and TNFalpha were more expressed in arsenic-treated MDDCs while IL6
transiently was down regulated. In general, our novel findings here strongly
suggest that low level of arsenic dysregulates four fundamental immune processes
of DCs. Mechanistically; this could explain the observed immunodeficiency
activity of Arsenic, and give direction for comprehension the pathogenesis of
Arsenic-induced diseases.
PMID- 28499615
TI - Why did arterial pressure not increase after fluid administration?
PMID- 28499614
TI - Considerations on the low adherence to clinical practice guidelines.
PMID- 28499613
TI - Effects of bisphenol A on incidence and severity of cardiac lesions in the NCTR
Sprague-Dawley rat: A CLARITY-BPA study.
AB - The goal of this study was to determine whether bisphenol A (BPA) had adverse
effects indicative of cardiac toxicity. As part of the "Consortium Linking
Academic and Regulatory Insights on BPA Toxicity" (CLARITY-BPA), study dams and
offspring were exposed by daily gavage to five doses of BPA ranging from 2.5 to
25000MUg/kg/day, 0.05 or 0.5MUg/kg/day 17alpha-ethinyl-estradiol (EE) or 0.3%
carboxymethylcellulose vehicle. Exposure-related effects were analyzed in
isolated hearts by quantitative morphometry and histopathology. No dose-related
changes in body weight were detected. Across all exposure groups including
vehicle controls, body weight of continuously dosed males was reduced compared to
males dosed only until PND21. Heart weight was increased only in females exposed
to EE, and consistent alterations in LV wall thickness were not observed.
Exposure-related changes in collagen accumulation were minor and limited to
highest EE exposure groups with increased collagen accumulation in PND21 males.
Decreased collagen was observed in hearts of BPA or EE exposed females at PND90
and PND180. In BPA or EE treated females cardiomyopathy incidence and severity
was significantly increased compared to control females at PND21 with myocardial
degeneration observed in both males and females at PND21 and PND90.
PMID- 28499617
TI - Community-based Outcomes of Open versus Robot-assisted Radical Prostatectomy.
AB - BACKGROUND: Identifying the optimal surgical approach for patients with localized
prostate cancer (PCa) managed in the community setting remains controversial due
to the lack of robust, prospective data. OBJECTIVE: To assess surgical outcomes
and changes in urinary and sexual quality of life (QOL) over time in patients
undergoing radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS: Our
study included patients enrolled in Cancer of the Prostate Strategic Urologic
Research Endeavor (CaPSURE), a large, prospective, mostly community-based,
nationwide PCa registry, who underwent RP between 2004 and 2016. INTERVENTION:
Open (ORP) versus robot-assisted radical prostatectomy (RARP) for localized PCa.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Demographic and clinicopathologic
data and surgical outcomes were compared between ORP and RARP. Self-reported,
validated questionnaires (scaled 0-100 with higher numbers indicating better
function) were used to evaluate urinary and sexual QOL at different time points.
Repeated measures mixed-models assessed changes in function and bother over time
in each domain. RESULTS AND LIMITATIONS: Among 1892 men (n = 1137 ORP; n = 755
RARP), Cancer of the Prostate Risk Assessment score, Gleason grade at biopsy and
RP, and pT-stage were lower in ORP patients (all p < 0.01). Men undergoing RARP
had comparable surgical margin rates, lymph node yields, and biochemical
recurrence rates. In a subset analysis with 1451 men reporting baseline and
follow-up QOL data, ORP patients reported superior scores in urinary incontinence
(ORP mean +/- standard deviation 69 +/- 26 vs RARP 62 +/- 27) and bother (ORP
75+/-29 vs RARP 68+/-28, both p < 0.01) only in the 1st yr after RP. Differences
in sexual outcomes did not differ between groups, nor did any QOL scores beyond 1
yr. Limitations include a decrease in the rate of questionnaire response during
follow-up, potential selection biases in terms of patient assignment to ORP
versus RARP and survey completion rates, and the fact that RARP cases likely
included the initial learning curve for the CaPSURE surgeons. CONCLUSIONS: Most
patients experienced changes in urinary and sexual QOL in the 1st 3 yr following
RP. The pattern of recovery over time was similar between ORP and RARP groups.
Patients should not expect different oncologic or QOL outcomes based on surgical
approach. PATIENT SUMMARY: Aside from a small, early, and temporary advantage in
terms of urinary incontinence and bother favoring open surgery, minimal
differences in outcomes are observed when comparing men who undergo open versus
robot-assisted prostatectomy in the community setting.
PMID- 28499616
TI - Effective analgesic doses of tramadol or tapentadol induce brain, lung and heart
toxicity in Wistar rats.
AB - Tramadol and tapentadol are extensively prescribed for the treatment of moderate
to severe pain. Although these drugs are very effective in pain treatment, the
number of intoxications and deaths due to both opioids is increasing, and the
underlying toxic mechanisms are not fully understood. The present work aimed to
study the potential biochemical and histopathological alterations induced by
acute effective (analgesic) doses of tramadol and tapentadol, in Wistar rats.
Forty-two male Wistar rats were divided into different groups: a control,
administered with normal saline solution, and tramadol- or tapentadol-treated
groups (10, 25 or 50mg/kg - typical effective analgesic dose, intermediate and
maximum recommended doses, respectively). 24h after intraperitoneal
administration, biochemical and oxidative stress analyses were performed in
blood, and specimens from brain, lung and heart were taken for histopathological
and oxidative stress studies. Both drugs caused an increase in the AST/ALT ratio,
in LDH, CK and CK-MB activities in serum samples, and an increase in lactate
levels in serum and brain samples. Oxidative damage, namely protein oxidation,
was found in heart and lung tissues. In histological analyses, tramadol and
tapentadol were found to cause alterations in cell morphology, inflammatory cell
infiltrates and cell death in all tissues under study, although tapentadol caused
more damage than tramadol. Our results confirmed the risks of tramadol exposure,
and demonstrated the higher risk of tapentadol, especially at high doses.
PMID- 28499618
TI - Applying Precision Oncology to Renal Cell Carcinoma: Emerging Challenges.
PMID- 28499619
TI - Reply to Tuomas Mirtti and Tero Aittokallio's Letter to the Editor re: Fatemeh
Seyednasrollah, Mehrad Mahmoudian, Liisa Rautakorpi, et al. How Reliable are
Trial-based Prognostic Models in Real-world Patients with Metastatic Castration
resistant Prostate Cancer? Eur Urol. 2017;71:838-40. Clinical Utility of Trial
estimated Prognostic Models.
PMID- 28499620
TI - Re: Fatemeh Seyednasrollah, Mehrad Mahmoudian, Liisa Rautakorpi, et al. How
Reliable are Trial-based Prognostic Models in Real-world Patients with Metastatic
Castration-resistant Prostate Cancer? Eur Urol. 2017;71:838-40.
PMID- 28499621
TI - An adaptive positivity thresholding method for automated Ki67 hotspot detection
(AKHoD) in breast cancer biopsies.
AB - The proliferative activity of breast cancer tissue can be estimated using the
Ki67 biomarker. The percentage of positivity of such biomarker is correlated with
proliferation and consequently with the prognosis of a breast tumor. Ki67 marked
tissue samples are analyzed by an experienced pathologist who identifies the most
active areas of tumor cell proliferation called hotspots, and estimates the
positivity of each case. A method for the Automated Ki67 Hotspot Detection
(AKHoD) is presented in this work. The main objective of the AKHoD method is to
automatically and efficiently provide the pathologist with suggestions about Ki67
hotspot areas as a decision support. The input of AKHoD is a digital slide that
is divided in tiles. For each tile, AKHoD provides a rough estimate of positivity
and cellularity, summarized in very low resolution positivity and cellularity
images. In a second step, an adaptive thresholding is applied to such positivity
image to identify the most positive connected and convex areas, within
cellularity limits set by current guidelines (that is, 500-2000). The method has
been preliminarily validated on 50 digital slides for which three expert
pathologists provided gold standard hotspots. 82% of the gold standard hotspots
have been successfully recognized by the system, spending an average of 54s per
slide. While further validation is needed taking into account also patients
follow-up, this first experimentation suggests that the proposed method could be
adequate for supporting the pathologist in hotspot detection.
PMID- 28499622
TI - m6A in mRNA: An Ancient Mechanism for Fine-Tuning Gene Expression.
AB - Modifications in mRNA constitute ancient mechanisms to regulate gene expression
post-transcriptionally. N6-methyladenosine (m6A) is the most prominent mRNA
modification, and is installed by a large methyltransferase complex (the m6A
'writer'), not only specifically bound by RNA-binding proteins (the m6A
'readers'), but also removed by demethylases (the m6A 'erasers'). m6A mRNA
modifications have been linked to regulation at multiple steps in mRNA
processing. In analogy to the regulation of gene expression by miRNAs, we propose
that the main function of m6A is post-transcriptional fine-tuning of gene
expression. In contrast to miRNA regulation, which mostly reduces gene
expression, we argue that m6A provides a fast mean to post-transcriptionally
maximize gene expression. Additionally, m6A appears to have a second function
during developmental transitions by targeting m6A-marked transcripts for
degradation.
PMID- 28499623
TI - Response to Letter to the Editor on "Long-Term Results of Total Hip Arthroplasty
With Shortening Subtrochanteric Osteotomy in Crowe IV Developmental Dysplasia".
PMID- 28499624
TI - Acetabular Placement Accuracy With the Direct Anterior Approach Freehand
Technique.
AB - BACKGROUND: Acetabular cup placement in total hip arthroplasty (THA) has been
recognized as an important factor in operative success, and accurate cup
placement has been the impetus for novel medical technologies. METHODS: This
article examines the cup placement in 955 THAs using a freehand Direct Anterior
Approach on a standard operating table. Acetabular anteversion and inclination
were determined using the circle theorem. Measurements were divided into safe
zone placement determined by Callanan et al as 5 degrees -25 degrees for
anteversion and 30 degrees -45 degrees for inclination, as well as by Lewinnek
et al as 5 degrees -25 degrees for anteversion and 30 degrees -50 degrees for
inclination. Dislocation rate was determined and correlated to safe zone
placement. RESULTS: Although technology has advanced for cup placement, this
investigation shows that a freehand technique demonstrates 0.31% dislocation
after THA with an accuracy of 85% for the Lewinnek safe zone and 61% for
Callanan, potentially because of the sparing of the posterior hip capsule.
CONCLUSION: The direct anterior approach to the hip on a regular operating table
is safe and reliable. Our results demonstrate improvement in cup positioning
compared with other freehand techniques. Surgeon awareness and control of the
position of the pelvis within space optimizes acetabular component accuracy and
precision without the need for special equipment, such as intraoperative
fluoroscopy.
PMID- 28499625
TI - Range of Motion Simulation of Hip Joint Movement During Salat Activity.
AB - BACKGROUND: Impingement of an artificial hip joint because of limited range of
motion (RoM) during human activity is one of the main sources of hip joint
failure. The aim of this article is to simulate the RoMs of hip joints during
salat, the practice of formal worship in Islam. METHODS: Salat consists of
several stages which can be represented with a cycle (raka'ah). Every raka'ah
consists of standing, bowing (ruku'), straightening up (i'tidal), transition of
standing toward prostrating, prostrating (sujud), and sitting. A virtual skeleton
model was used to analyze the motion during salat for the possibility of the
impingement occurrence. RESULTS: The results of the simulation were presented in
terms of maximum flexion, abduction, and internal or external rotation. The
results also showed that the prostration position is similar in RoM with the
Japanese zarei position and similar in RoM to pick up an object while sitting on
a chair. CONCLUSION: Specific aspects of salat such as the difference in position
of the 2 legs at the last sitting position create an extreme RoM which in turn
results in a high risk of impingement.
PMID- 28499626
TI - Carbon Dioxide Exposure Resulting From Hood Protective Equipment Used in Joint
Arthroplasty Surgery.
AB - BACKGROUND: To protect both the surgeon and patient during procedures, hooded
protection shields are used during joint arthroplasty procedures. Headache,
malaise, and dizziness, consistent with increased carbon dioxide (CO2) exposure,
have been anecdotally reported by surgeons using hoods. We hypothesized that
increased CO2 concentrations were causing reported symptoms. METHODS: Six healthy
subjects (4 men) donned hooded protection, fan at the highest setting. Arm cycle
ergometry at workloads of 12 and 25 watts (W) simulated workloads encountered
during arthroplasty. Inspired O2 and CO2 concentrations at the nares were
continuously measured at rest, 12 W, and 25 W. At each activity level, the fan
was deactivated and the times for CO2 to reach 0.5% and 1.0% were measured.
RESULTS: At rest, inspired CO2 was 0.14% +/- 0.04%. Exercise had significant
effect on CO2 compared with rest (0.26% +/- 0.08% at 12 W, P = .04; 0.31% +/-
0.05% at 25 W, P = .003). Inspired CO2 concentration increased rapidly with fan
deactivation, with the time for CO2 to increase to 0.5% and 1.0% after fan
deactivation being rapid but variable (0.5%, 12 +/- 9 seconds; 1%, 26 +/- 15
seconds). Time for CO2 to return below 0.5% after fan reactivation was 20 +/- 37
seconds. CONCLUSION: During simulated joint arthroplasty, CO2 remained within
Occupational Safety and Health Administration (OSHA) standards with the fan at
the highest setting. With fan deactivation, CO2 concentration rapidly exceeds
OSHA standards.
PMID- 28499627
TI - Clinical application of MOSkin dosimeters to rectal wall in vivo dosimetry in
gynecological HDR brachytherapy.
AB - PURPOSE: Three MOSkins dosimeters were assembled over a rectal probe and used to
perform in vivo dosimetry during HDR brachytherapy treatments of vaginal cancer.
The purpose of this study was to verify the applicability of the developed tool
to evaluate discrepancies between planned and measured doses to the rectal wall.
MATERIALS AND METHODS: MOSkin dosimeters from the Centre for Medical Radiation
Physics are particularly suitable for brachytherapy procedures for their ability
to be easily incorporated into treatment instrumentation. In this study, 26
treatment sessions of HDR vaginal brachytherapy were monitored using three MOSkin
mounted on a rectal probe. A total of 78 measurements were collected and compared
to doses determined by the treatment planning system. RESULTS: Mean dose
discrepancy was determined as 2.2+/-6.9%, with 44.6% of the measurements within
+/-5%, 89.2% within +/-10% and 10.8% higher than +/-10%. When dose discrepancies
were grouped according to the time elapsed between imaging and treatment (i.e.,
group 1: <=90min; group 2: >90min), mean discrepancies resulted in 4.7+/-3.6% and
7.1+/-5.0% for groups 1 and 2, respectively. Furthermore, the position of the
dosimeter on the rectal catheter was found to affect uncertainty, where highest
uncertainties were observed for the dosimeter furthest inside the rectum.
CONCLUSIONS: This study has verified MOSkin applicability to in-patient dose
monitoring in gynecological brachytherapy procedures, demonstrating the
dosimetric rectal probe setup as an accurate and convenient IVD instrument for
rectal wall dose verification. Furthermore, the study demonstrates that the
delivered dose discrepancy may be affected by the duration of treatment planning.
PMID- 28499628
TI - A real world wearable cardioverter defibrillator experience - Very high
appropriate shock rate in ischemic cardiomyopathy patients at a European single
center.
AB - BACKGROUND: The wearable cardioverter defibrillator (WCD) has emerged as a
valuable tool to protect patients with increased risk of sudden cardiac death
(SCD). We sought to characterize WCD patients and to analyze predictors of
ventricular arrhythmia (VA) occurrence and WCD shock delivery. METHODS AND
RESULTS: One hundred fourteen patients with WCD use were included in the study.
Indications were mainly ischemic cardiomyopathy (ICM; 31.6%), non-ICM (45.6%) and
explantation of implantable cardioverter defibrillator due to device infection
(11.4%). We observed sustained VA in 9.6% of the study population and 6.1%
received an appropriate shock. VA occurred in 16.7% of ICM, 3.8% of non-ICM and
15.4% of patients with device infection. CONCLUSIONS: Our data demonstrate a very
high rate of sustained VA in patients at risk for SCD during WCD use. ICM
patients, including those with recent MI, bore the highest risk.
PMID- 28499629
TI - Nonobstructive Reproductive Tract Anomalies: A Review of Surgical Management.
AB - Mullerian anomalies include a spectrum of anatomic variants of the genital tract
arising from abnormal embryologic development, ranging from incomplete resorption
of uterine septa to complete vaginal agenesis. Nonobstructive anomalies are often
recognized later than obstructive anomalies, because women do not present with
pain. However, nonobstructive anomalies frequently have a negative impact on
sexual and reproductive health, and careful evaluation and management of these
disorders is warranted. This review focuses on the surgical management of
nonobstructive Mullerian anomalies.
PMID- 28499630
TI - Effect of surface alkali-based treatment of titanium implants on ability to
promote in vitro mineralization and in vivo bone formation.
AB - : This study investigated whether a novel alkali-based surface modification
enhances in vitro mineralization as well as in vivo bone formation around
titanium (Ti) implants in a femoral condyle model of 36 male Wister rats. All
implant surfaces were grit-blasted and then received either acid-etching
treatment, alkali-based treatment, or were left untreated (controls).
Histological and histomorphometrical analyses were performed on retrieved
specimens after 4 and 8weeks of healing to assess peri-implant bone formation.
Results of implants surface characterisation showed notable differences in the
topography and composition of alkali-treated surfaces, reflecting the formation
of submicron-structured alkali-titanate layer. In the in vitro test, alkali
treated Ti surfaces showed the ability to stimulate mineralization upon soaking
in simulated body fluid (SBF). In vivo histomorphometrical analyses showed
similar values for bone area (BA%) and bone-to-implant contact (BIC%) for all
experimental groups after both 4- and 8-week implantation periods. In conclusion,
the surface topography and composition of the grit-blasted Ti implants was
significantly modified using alkali-based treatment. With respect to the present
in vivo model, the biological performance of alkali-treated Ti implants is
comparable to the commercially available, grit-blasted, acid-etched Ti implants.
STATEMENT OF SIGNIFICANCE: Since success rate of dental implants might be
challenged in bone of low density, an optimum implant surface characteristic is
demanding. In this work, alkali treatment of Ti implants showed significant
advantage of surface mineralization upon soaking in simulated body fluid. Using
an in vivo rat model, Ti surfaces with either acid-etching treatment or alkali
based treatment evoked robust bone formation around Ti implants. Such information
may be utilized for the advancement of biomaterials research for bone implants in
future.
PMID- 28499631
TI - Extrafibrillar collagen demineralization-based chelate-and-rinse technique
bridges the gap between wet and dry dentin bonding.
AB - : Limitations associated with wet-bonding led to the recent development of a
selective demineralization strategy in which dentin was etched with a reduced
concentration of phosphoric acid to create exclusive extrafibrillar
demineralization of the collagen matrix. However, the use of acidic conditioners
removes calcium via diffusion of very small hydronium ions into the
intrafibrillar collagen water compartments. This defeats the purpose of limiting
the conditioner to the extrafibrillar space to create a collagen matrix
containing only intrafibrillar minerals to prevent collapse of the collagen
matrix. The present work examined the use of polymeric chelators (the sodium salt
of polyacrylic acid) of different molecular weights to selectively demineralize
extrafibrillar dentin. These polymeric chelators exhibit different affinities for
calcium ions (isothermal titration calorimetry), penetrated intrafibrillar dentin
collagen to different extents based on their molecular sizes (modified size
exclusion chromatography), and preserve the dynamic mechanical properties of
mineralized dentin more favorably compared with completely demineralized
phosphoric acid-etched dentin (nanoscopical dynamic mechanical analysis).
Scanning and transmission electron microscopy provided evidence for retention of
intrafibrillar minerals in dentin surfaces conditioned with polymeric chelators.
Microtensile bond strengths to wet-bonded and dry-bonded dentin conditioned with
these polymeric chelators showed that the use of sodium salts of polyacrylic acid
for chelating dentin prior to bonding did not result in significant decline in
resin-dentin bond strength. Taken together, the findings led to the conclusion
that a chelate-and-rinse conditioning technique based on extrafibrillar collagen
demineralization bridges the gap between wet and dry dentin bonding. STATEMENT OF
SIGNIFICANCE: The chelate-and-rinse dental adhesive bonding concept
differentiates from previous research in that it is based on the size-exclusion
characteristics of fibrillar collagen; molecules larger than 40kDa are prevented
from accessing the intrafibrillar water compartments of the collagen fibrils.
Using this chelate-and-rinse extrafibrillar calcium chelation concept, collagen
fibrils with retained intrafibrillar minerals will not collapse upon air-drying.
This enables adhesive infiltration into the mineral-depleted extrafibrillar
spaces without relying on wet-bonding. By bridging the gap between wet and dry
dentine bonding, the chelate-and-rinse concept introduces additional insight to
the field by preventing exposure of endogenous proteases via preservation of the
intrafibrillar minerals within a collagen matrix. If successfully validated, this
should help prevent degradation of resin-dentine bonds by collagenolytic enzymes.
PMID- 28499632
TI - A comprehensive study of layer-specific morphological changes in the
microstructure of carotid arteries under uniaxial load.
AB - : The load bearing properties of large blood vessels are principally conferred by
collagen and elastin networks and their microstructural organization plays an
important role in the outcomes of various arterial pathologies. In particular,
these fibrous networks are able to rearrange and reorient spatially during
mechanical deformations. In this study, we investigate for the first time whether
these well-known morphological rearrangements are the same across the whole
thickness of blood vessels, and subsequently if the underlying mechanisms that
govern these rearrangements can be predicted using affine kinematics. To this
aim, we submitted rabbit carotid samples to uniaxial load in three distinct
deformation directions, while recording live images of the 3D microstructure
using multiphoton microscopy. Our results show that the observed realignment of
collagen and elastin in the media layer, along with elastin of the adventitia
layer, remained limited to small angles that can be predicted by affine
kinematics. We show also that collagen bundles of fibers in the adventitia layer
behaved in significantly different fashion. They showed a remarkable capacity to
realign in the direction of the load, whatever the loading direction. Measured
reorientation angles of the fibers were significantly higher than affine
predictions. This remarkable property of collagen bundles in the adventitia was
never observed before, it shows that the medium surrounding collagen in the
adventitia undergoes complex deformations challenging traditional hyperelastic
models based on mixture theories. STATEMENT OF SIGNIFICANCE: The biomechanical
properties of arteries are conferred by the rearrangement under load of the
collagen and elastin fibers making up the arterial microstructure. Their
kinematics under deformation is not yet characterized for all fiber networks. In
this respect we have submitted samples of arterial tissue to uniaxial tension,
simultaneously to confocal imaging of their microstructure. Our method allowed
identifying for the first time the remarkable ability of adventitial collagen
fibers to reorient in the direction of the load, achieving reorientation
rotations that exceeded those predicted by affine kinematics, while all other
networks followed the affine kinematics. Our results highlight new properties of
the microstructure, which might play a role in the outcomes of vascular
pathologies like aneurysms.
PMID- 28499633
TI - Controllable release of nitric oxide and doxorubicin from engineered nanospheres
for synergistic tumor therapy.
AB - : NaYF4:Yb,Er upconversion nanoparticles (UCNPs) capped with long-chain
carboxylic acid were synthesized and then conjugated with chitosan (CS) in the
aid of N-hydroxysuccinimide. The resultant nanocompound was integrated with
doxorubicin (DOX) and Roussin's black salt (RBS), a photosensitive nitric oxide
(NO) donor to produce stimuli-responsive UCNPs(DOX)@CS-RBS nanospheres as
nanocarriers for controllable drug delivery. On the one hand, the encapsulated
UCNPs can efficiently absorb NIR photons and convert them into visible photons to
trigger NO release. On the other hand, the entrapped DOX can be released at
lowered pH from the swollen nanospheres caused by stretched oleoyl-CS chains
under acidic conditions. The UCNPs(DOX)@CS-RBS nanospheres exhibit great
therapeutic efficacy, which is attributable to the combination of NO and DOX
releases based on NO dose-dependent mechanisms. This study highlights the
controllable release of NO and DOX from the same nanocarriers and the synergistic
therapeutic effect on tumors, which could give new insights into improving cancer
nanotherapeutics. STATEMENT OF SIGNIFICANCE: In this paper, core-shell structured
UCNPs(DOX)@CS-RBS nanospheres have been designed and synthesized via a step-by
step procedure. The stimuli-responsive UCNPs(DOX)@CS-RBS nanospheres act as
nanocarriers for controllable drug delivery towards cancer therapy. The
encapsulated UCNPs can efficiently absorb NIR photons and convert them into
visible light to trigger NO release. Meanwhile, the entrapped DOX can be released
from the swollen nanospheres caused by stretched oleoyl-CS chains at lowered pH
typical of intracellular environment. Synergistic cancer therapy will be achieved
through the combination of NO and DOX releases based on NO dose-dependent
mechanisms. This study provides new drug nanocarriers with high antitumor
efficacy for synergistic cancer therapy.
PMID- 28499634
TI - A 'degradable' poly(vinyl alcohol) iron oxide nanoparticle hydrogel.
AB - : Polymeric materials that contain magnetic nanoparticles are extremely useful in
many applications including as multifunctional drug carriers, imaging contrast
agents, or scaffold material. There is a need for biomaterials with appropriate
chemical, mechanical, and magnetic properties that also have the ability to
degrade or dissolve over time so they can be eliminated from the body following
use. In this work, we explore the use of iron oxide nanoparticle (IONP) formation
in poly(vinyl alcohol) (PVA) as a crosslinking method in conjunction with
physical crosslinking achieved using low temperature thermal cycling (LTTC). PVA
IONP hydrogels were fabricated and characterized. IONPs contribute to the
crosslinking of the PVA-IONP material, and their subsequent removal reduces
crosslinking, and therefore stability, of the material, allowing dissolution to
occur. Dissolution studies were performed on PVA-IONP hydrogels and dissolution
was compared for films in solutions of varying pH, in the presence of iron
chelating agents, and in simulated physiological and tumor conditions in cell
culture media. Iron release, mass loss, and mechanical testing data was
collected. This work demonstrates the ability of this biomaterial to 'degrade'
over time, which may be very advantageous for applications such as drug delivery.
This importance of this work extends to other areas such as the use of stimuli
responsive hydrogels. STATEMENT OF SIGNIFICANCE: This manuscript explores the
stability of an iron oxide nanoparticle (IONP)-containing, physically crosslinked
poly(vinyl alcohol) (PVA) hydrogel. The PVA-IONP hydrogel's stability is imparted
through crosslinks created through a low temperature thermal cycling process and
through the IONPs. Subsequent IONP removal reduces crosslinks so material
dissolution can occur, resulting in a 'degradable' and multifunctional
biomaterial. PVA-IONP films were fabricated, characterized and evaluated in terms
of dissolution in solutions of varying pH and in the presence of chelating
agents. Iron release, mass loss, and mechanical testing data demonstrate the
ability of the PVA-IONP biomaterial to 'degrade' over time. This degradability
has not yet been demonstrated for crosslinked PVA hydrogels. These results are
relevant to the development of degradable multifunctional drug carriers, image
contrast agents, or magnetic scaffold materials.
PMID- 28499635
TI - Adenosine A2A receptors are up-regulated and control the activation of human
alveolar macrophages.
AB - Chronic inflammatory lung diseases remain a health concern and new anti
inflammatory treatments are needed. Targeting adenosine A2A receptors (A2AR)
affords robust anti-inflammatory effects in animal models, but the translation of
this promising strategy to humans has been challenging, possibly due to
interspecies differences in receptor distribution and effects. Thus, we now
assessed the efficiency of a selective A2AR agonist to control the activation of
fresh human alveolar inflammatory cells. We collected bronchoalveolar lavage
fluid from patients with interstitial lung disease and loaded alveolar cells with
the intracellular free calcium probe FURA-2/AM. Calcium transients were then
recorded in response to superfusion with a proinflammatory peptide (N
formylmethionyl-leucyl-phenylalanine - FMLP), in the absence or presence of the
selective A2AR agonist CGS21680. In a second experiment, cells were continuously
exposed to FMLP and A2AR density was assessed by immunocytochemistry. Sixteen
patients were included, nine for analysis of calcium transients, and seven for
immunocytochemistry. When alveolar macrophages were exposed to 100 nM FMLP for
120 s, a peak elevation of intracellular free calcium levels (97.0% over
baseline) was recorded; CGS21680 (100 and 300 mM) significantly reduced this peak
to 89.5% and 81.5%, respectively. The immunofluorescence analysis revealed a time
dependent increase of A2AR density in alveolar macrophage upon exposure to 1 MUM
FMLP, up to 148% of control at 6 h. These results show that pro-inflammatory
stimuli up-regulate A2AR and their activation dampens the impact of pro
inflammatory stimuli. This supports that targeting A2AR is a promising therapy
for human lung inflammatory diseases, especially for diseases with a strong
inflammatory component.
PMID- 28499636
TI - [Is there a role for therapeutic education to prevent acute COPD exacerbations?]
PMID- 28499637
TI - [Preventive measures after acute COPD exacerbations].
PMID- 28499638
TI - [Appropriate investigations during an acute COPD exacerbation requiring
hospitalization].
PMID- 28499639
TI - [Appropriate investigations during acute COPD exacerbations in community-based
practice].
PMID- 28499640
TI - [What is the place for biomarkers during acute COPD exacerbations?]
PMID- 28499641
TI - Outcomes of research biopsies in clinical trials of EGFR mutation-positive non
small cell lung cancer patients pretreated with EGFR-tyrosine kinase inhibitors.
AB - BACKGROUND/PURPOSE: Research biopsies (RBs) are crucial for developing novel
molecular targeted agents. However, the safety and diagnostic yields of RBs have
not been investigated in EGFR mutation-positive non-small cell lung cancer
(NSCLC) patients pretreated with epidermal growth factor receptor (EGFR) tyrosine
kinase inhibitors (TKIs). METHODS: We searched the medical records of NSCLC
patients who participated in lung cancer clinical trials and underwent mandatory
RBs between 2012 and 2014 at our institution. Only patients with EGFR mutation
positive NSCLC pretreated with at least 1 EGFR-TKI were enrolled. RESULTS: Of 140
enrolled patients, 73 (52.1%) and 59 (42.1%) had exon 19 deletions and exon 21
L858R mutation, respectively. Before RBs, 108 (77.1%), 83 (59.3%), and 36 (25.7%)
patients had been treated with gefitinib, erlotinib, and afatinib, respectively.
Computed tomography-guided percutaneous core needle biopsy was the most
frequently used modality among 181 RBs performed (50.8%), followed by
ultrasonography-guided (32.0%) and endoscopic RBs (16.0%). The most common RB
sites were the lung (69.6%), pleura (8.8%), and liver (6.1%). Pathologic
examinations revealed malignant cells in most RB specimens (72.9%). Complications
due to RBs included pneumothorax (11.6%), bleeding (6.1%), and infection (1.1%).
Only 1 patient required chest tube placement for pneumothorax, and 2 patients
underwent endotracheal intubation because of bleeding. CONCLUSION: RBs in this
patient population were generally safe. Pneumothorax was the most frequent
complication; bleeding, while infrequent, increased the risk of severe events.
The diagnostic yields and complications of any particular modality should
therefore be discussed with prospective clinical trial participants.
PMID- 28499642
TI - Efficiency of four currently used decontamination conditionings in Romania
against Aspergillus and Candida strains.
AB - INTRODUCTION: Efficacy of four commercial biocidal products (noted A to D), using
manufacturers' recommendations, and a contact time of 30minutes, were evaluated
in the purpose of standard SR EN1657: 2006 adapted. METHODS: Were used four
strains, two as reference: Aspergillus brasiliensis (niger) (ATCC 16404) and
Candida albicans (ATCC 10231), and two isolates: Aspergillus flavus and
respectively Aspergillus fumigatus. The inoculum plates containing Malt Extract
Agar (MEA) were incubated 48h for C. albicans and 72hours for Aspergillus spp.
The standard SR EN1657: 2006 adapted was conducted in two phases: the test
cultures preparation and the method validation. Method validation included: the
control of experimental conditions and of neutralizant solution, and the method
verification. RESULTS: Results revealed that three from the four tested products
(A, B and D) had exerted biocidal effect on the studied strains at the
recommended concentrations, the registered CFU values being reduced by more than
4 log10, conversely in the case of the product (C), applied against A. fumigatus
at the recommended concentration of 2%, the biocidal effect was not detected,
fact confirmed also by the CFU's value (3.59 log10). The biocide retested at a
greater concentration (of 5%), showed a biocidal effect against A. fumigatus
after 30minutes, the CFU value being reduced, by more than 5.29 log10, evidencing
the resistance emergence of A. fumigatus under the repeated pressure of biocides.
CONCLUSION: It is re-confirming that merely the "chemical" defense measures to
defuse the fungi's strategies become unproductive.
PMID- 28499643
TI - Pharmacokinetic profile of bilberry anthocyanins in rats and the role of glucose
transporters: LC-MS/MS and computational studies.
AB - The aim of the present investigation was to better understand the pharmacokinetic
profile of bilberry (Vaccinium Myrtillus) anthocyanins and the role of glucose
transporters (sGLT1 and GLUT2) on their absorption. In particular, the absorption
of 15 different anthocyanins contained in a standardized bilberry extract
(Mirtoselect(r)) was measured in rats by a validated LC-ESI-MS/MS approach. The
plasma concentration peak (Cmax) of 11.1ng/mL was reached after 30min and fasting
condition significantly increased the bioavailability of anthocyanins by more
than 7 fold in respect to fed rats. Glucose co-administration did not interfere
with the overall anthocyanin uptake. Bioavailability of each anthocyanin was then
estimated by comparing the relative content in plasma vs extract. The 15
anthocyanins behaved differently in term of bioavailability and both the aglycone
and the sugar moiety were found to affect the absorption. For instance,
arabinoside moiety was detrimental while cyanidin enhanced bioavailability.
Computational studies permitted to rationalize such results, highlighting the
role of glucose transporters (sGLT1 and GLUT2) in anthocyanins absorption. In
particular a significant correlation was found for the 15 anthocyanins between
sGLT1 and GLUT2 recognition and absorption.
PMID- 28499644
TI - Simple and rapid LC-MS method for the determination of circulating albumin
microheterogeneity in veal calves exposed to heat stress.
AB - Heat stress has a major impact on veal calves welfare and productivity. Prolonged
exposure to warm temperature is associated with several alterations of
physiologic processes and increased systemic inflammation and oxidative stress.
Bovine serum albumin (BSA) is the most abundant plasma protein and, besides the
regulation of osmotic pressure, carries several additional functions, including
antioxidant, immunomodulatory, binding and transport activities. Such non-oncotic
properties are closely related to structural integrity of the circulating
molecule and may be compromised in stressful microenvironments as it occurs in
heat stressed animals. Thus, in the present study we developed and validated an
LC-MS analytical technique for the characterization of circulating BSA
microheterogeneity in veal calves exposed to heat stress. The method was
specifically tailored to the structural characteristics of the BSA molecule as
well as to the complexity of the biological samples, allowing the identification
of several BSA isoforms, each characterized by a specific structural defect. The
mass spectrometry based approach enabled the identification of BSA isoforms with
reversible and irreversible oxidation and/or glycation and the native BSA, the
only isoform endowed with structural and functional integrity. We found that, in
veal calves, heat stress is associated to a significant reduction of the native
BSA and to a significant increment of the reversibly and irreversibly oxidized
BSA. Then, by monitoring the BSA microheterogeneity over a period of moderate
heat stress, we found that the native BSA as well as the glycated BSA increased
significantly during the recovery period. Based on our results the analysis of
the BSA microheterogeneity could represent a novel biomarker for the assessment
of animal welfare during environmental stressful conditions.
PMID- 28499645
TI - Healing: Moving Toward Health and Wholeness.
PMID- 28499646
TI - Dancing partners at the ball: Rational selection of next generation anti-CD20
antibodies for combination therapy of chronic lymphocytic leukemia in the novel
agents era.
AB - The anti-CD20 antibodies represent a major advancement in the therapeutic options
available for chronic lymphocytic leukemia. The addition of rituximab, ofatumumab
and obinutuzumab to various chemotherapy regimens has led to considerable
improvements in both response and survival. Ocaratuzumab, veltuzumab and
ublituximab are currently being explored within the trial setting. We review the
current status of these antibodies, and discuss how their mechanisms of action
may impact on the choice of combinations with novel small molecule agents.
PMID- 28499647
TI - Commentary to "Assessment of Competence in EVAR Procedures - A Novel Rating Scale
Developed by the Delphi Technique".
PMID- 28499648
TI - Ovarian cancer spheroid shrinkage following continuous exposure to cisplatin is a
function of spheroid diameter.
AB - OBJECTIVE: Most ovarian cancer patients present with advanced-stage disease,
disseminated in the peritoneal cavity. Standard treatment involves surgical
resection of all visible tumor, followed by delivery of systemic therapy.
Patients with advanced-stage disease may be candidates for intraperitoneal (IP)
chemotherapy following surgical debulking. Recent clinical trials have created
controversy regarding the benefits of this approach. Previous clinical trials
report that patients with microscopic residual disease respond best to IP
therapy. The goal of this study was to determine the relationship between tumor
size and the efficacy of continuous chemotherapy. METHODS: Small and large
ovarian cancer spheroids (derived from UCI101 and A2780 cell lines) were exposed
to short-term high (modeling an IP injection, "IP") or prolonged, low cisplatin
concentrations (modeling an implanted device, "device"), which have been
previously shown to be less toxic. Spheroid diameter was measured at various time
points via image analysis and used to quantify tumor shrinkage over the course of
treatment. RESULTS: We show that "IP" doses more effectively shrink large
spheroids when the same cumulative dose is administered with both treatments, but
that both regimens similarly treat small spheroids. We also demonstrate that
higher cumulative "device" doses are most effective at shrinking large spheroids.
CONCLUSIONS: These results support the hypothesis that intratumoral drug
distribution following IP treatment is diffusion-controlled. An implanted device
that continuously delivers low doses of IP chemotherapy would, therefore, be
maximally effective against microscopic tumors.
PMID- 28499649
TI - A SEER-Medicare analysis of the impact of metformin on overall survival in
ovarian cancer.
AB - OBJECTIVE: Determine whether metformin use is associated with improved survival
in patients with ovarian, fallopian tube or primary peritoneal cancer. METHODS:
All patients with a diagnosis of first epithelial ovarian cancer from 2007 to
2011 in the combined SEER-Medicare database were identified from the SEER
registry primary site codes. Comorbidities, procedures and cancer treatment ICD-9
and HCPCS codes were used to search the Medicare claims files. Medication use was
determined with National Drug Codes using the Medicare Part D event files. The
primary outcome, overall survival, was assessed between metformin users and non
users using a Cox Proportional Hazards survival model. To control for
confounding, metformin users were matched to non-metformin users using propensity
scores. Effect of dosage on survival was assessed using discrete time survival
analysis with pooled logistic regression (PLR). RESULTS: There were 2291 cases
that met our inclusion criteria. Of these, 180 (7.9%) had been on metformin. The
median age was 73years, with the majority of the population being White (83.5%)
and treated with primary surgery (74.1%). Metformin use was not associated with
overall survival in the entire cohort (HR 0.96, 95% CI 0.75-1.23) or in the
matched sample cohort (HR 0.88, 95% CI 0.66-1.17). However, exploratory
regression with time-varying coefficients suggests a protective metformin effect
for women alive after 30months follow-up (HR=0.37, 95% 0.16-0.87). CONCLUSION: No
statistically significant association was observed between metformin use and
overall survival in a matched cohort of 360 ovarian cancer patients. However,
exploratory modeling suggests metformin use may be protective in a certain
subgroup of patients.
PMID- 28499651
TI - Bioprosthetic Aortic Valve Durability: A Meta-Regression of Published Studies.
AB - To compare structural valve deterioration (SVD) among bioprosthetic aortic valve
types, a PubMed search found 54 papers containing SVD-free curves extending to at
least 10 years. The curves were digitized and fit to Weibull distributions, and
the mean times to valve failure (MTTF) were calculated. Twelve valve models were
collapsed into four valve types: Medtronic (Medtronic, Minneapolis, MN) and
Edwards (Edwards Lifesciences, Irvine, CA) porcine; and Sorin (Sorin Group [now
LivaNova], London, United Kingdom) and Edwards pericardial. Meta-regression found
MTTF was associated with the patient's age, publication year, SVD definition, and
valve type. Sorin pericardial valves had significantly lower risk-adjusted MTTF
(higher SVD risk), and there were no significant differences in MTTF among the
other three valve types.
PMID- 28499650
TI - The Mesenchymal State Predicts Poor Disease-Free Survival in Resectable Non-Small
Cell Lung Cancer.
AB - BACKGROUND: The epithelial-mesenchymal transition (EMT) is thought to contribute
to the overall invasiveness of malignant cells. Expression of cluster of
differentiation (CD) 44 and CD90 mark the mesenchymal state in multiple
epithelial malignancies. Their role in lung cancer remains unclear, however. This
study evaluated the prognostic significance of CD44 and CD90 coexpression in
patients with resectable primary non-small cell lung cancer (NSCLC). METHODS:
This was a nonconcurrent cohort study of patients with resectable NSCLC,
stratified by the degree of expression of CD44/CD90 double-positive cells in
their primary tumor. Flow cytometry was used for immunophenotyping of freshly
isolated disaggregated tumor. We analyzed the relationship between expression of
CD44/CD90 and relapse-free survival. RESULTS: We evaluated 37 patients (18 men;
median age, 70 years) with NSCLC. For this group, the geometric mean proportion
of cells coexpressing CD44/CD90 was 0.52%. Expression of CD44/CD90 was
significantly elevated (24.4%, geometric mean) in 6 patients. The median relapse
free survival for patients with high CD44/CD90 coexpression was 7.7 months (95%
confidence interval, 4.2 to 11.7) compared with 40 months (95% confidence
interval, 18.2 to 77.8) for the group with low CD44/CD90 coexpression (p =
0.00006 by Mantel log-rank test). The assessment of risk based upon CD44/CD90
expression status was not correlated with pathologic staging (p = 0.073 by chi2).
CONCLUSIONS: High expression of CD44 and CD90 was associated with significantly
reduced relapse-free survival in NSCLC patients. These results suggest that CD44
and CD90 may be important markers of tumor progression in NSCLC.
PMID- 28499652
TI - Lack of Furosemide Responsiveness Predicts Acute Kidney Injury in Infants After
Cardiac Surgery.
AB - BACKGROUND: This was a retrospective study to determine whether lack of
furosemide responsiveness (LFR) predicts acute kidney injury (AKI) after
cardiopulmonary bypass surgery in infants. METHODS: Infants (less than 1 year of
age) undergoing cardiopulmonary bypass surgery, receiving routine postoperative
furosemide (0.8 to 1.2 mg/kg per dose between 8 and 24 hours after surgery) were
included. Urine output was measured 2 and 6 hours after furosemide dose. Lack of
furosemide responsiveness was defined a priori as urine output less than 1 mL .
kg-1 . h-1 after furosemide. Serum creatinine was corrected for fluid balance.
Acute kidney injury was determined using changes in uncorrected and corrected
serum creatinine. The predictive utility of LFR was assessed using receiver
operating characteristics curve analysis. RESULTS: We analyzed 568 infants who
underwent cardiopulmonary bypass. Eighty-one (14.3%) had AKI using uncorrected
serum creatinine; AKI occurred in 41 (7.2%) after correcting for fluid overload.
Patients with AKI had a lower response to furosemide (median urine output 2
hours: 1.2 versus 3.4 mL . kg-1 . h-1, p = 0.01; median urine output 6 hours: 1.3
versus 2.9 mL . kg-1 . h-1, p = 0.01). After creatinine correction, LFR predicts
AKI development (area under receiver-operating characteristics curve of 0.74 at 2
hours and 0.77 at 6 hours). After adjusting for surgical complexity using The
Society of Thoracic Surgeons/European Association for Cardiothoracic Surgery
mortality categories, the area under the receiver-operating characteristics curve
was 0.74 at 2 hours and 0.81 at 6 hours. Patients with urine output greater than
1 mL . kg-1 . h-1 were unlikely to have AKI (negative predictive value, 97%).
CONCLUSIONS: After correcting serum creatinine for fluid balance and adjusting
for surgical complexity, LFR performs fairly at 2 hours, whereas at 6 hours, LFR
is a good AKI predictor. Prospective studies are needed to validate whether
diuretic responsiveness predicts AKI.
PMID- 28499653
TI - Customized Hinged Covered Metallic Stents for the Treatment of Benign Main
Bronchial Stenosis.
AB - BACKGROUND: To address the limitations of silicone stents, we designed a hinged
self-expandable covered metallic stent. The aim of this study was to evaluate the
safety and efficacy of the customized stents in clinical applications. METHODS:
This was a retrospective analysis. Under conscious sedation and local anesthesia,
the stents were implanted or removed by interventional radiologists, with
fluoroscopic guidance. RESULTS: Of 24 patients with benign main bronchial
stenosis, stents were successfully placed in 21 (87.5%). The low-pressure balloon
before dilation failed in 1 case (4.17%) of left main bronchial cicatricial
stenosis. In 2 other cases (8.33%), stent placement was abandoned. Stents were
successfully removed between 29 and 103 days after the procedure. After stent
removal, the follow-up lasted for at least 12 months. Restenosis occurred only in
1 case (4.55%) owing to bronchial collapse 3 days after stent removal. Dyspnea
occurred in another case (4.55%) at 2 months after retrieval; recurrence was
confirmed using bronchoscopy, leading to a left pneumonectomy. CONCLUSIONS: The
described procedure is safe and easy to be performed and avoids the use of
intubation, bronchoscopy, and general anesthesia.
PMID- 28499654
TI - Hybrid Extracorporeal Membrane Oxygenation Using Avalon Elite Double Lumen
Cannula Ensures Adequate Heart/Brain Oxygen Supply.
AB - BACKGROUND: Differential hypoxia exists in peripheral venoarterial (VA)
extracorporeal membrane oxygenation (ECMO) patients with compromised lungs,
causing hypoxic damage to heart or brain. We proposed an Avalon Elite (Maquet,
Rastatt, Germany) double lumen cannula-based hybrid ECMO to add a venovenous (VV)
blood flow into the pulmonary circulation onto the existing VA ECMO circuit to
increase oxygen saturation in the left ventricle and ascending aorta, mitigating
heart/brain hypoxia. METHODS: This hybrid ECMO circuit consists of two cannulas
(27F Avalon Elite double lumen cannula from the inferior vena cava to the
superior vena cava to right atrium to inferior vena cava; 17F infusion cannula in
femoral artery), a blood pump, and a gas exchanger. This hybrid ECMO circuit was
tested in 7 adult sheep with simulated lung failure. Total ECMO blood flow (2.8
to 3.3 L/min) was split between VV and VA blood flow. The VV blood flow was
adjusted from 0% to 50% of total ECMO flow by approximately 10% increments.
RESULTS: In VA ECMO, simulated respiratory failure resulted in differential
hypoxia (low oxygen level in left ventricle and high oxygen level in abdominal
aorta). In hybrid ECMO, adding VV blood flow (10% to 50% of total ECMO flow) to
the VA ECMO circuit progressively increased left ventricle blood oxygen
saturation from 70% +/- 8% at zero VV blood flow (pure VA ECMO) to 82% +/- 6% at
300 mL/min VV blood flow, and 96% +/- 6% at 1,700 mL/min VV blood flow.
CONCLUSIONS: The Avalon Elite double-lumen cannula-based hybrid ECMO circuit is a
simple circuit that provides efficient performance and flexible VA/VV blood
distribution. In this hybrid ECMO circuit, incremental VV blood flow (10% to 50%)
progressively increased left ventricular blood oxygen level, ensuring adequate
heart and brain oxygen supply.
PMID- 28499655
TI - Validating the Thoracic Revised Cardiac Risk Index Following Lung Resection.
AB - BACKGROUND: The Thoracic Revised Cardiac Index (ThRCRI) is a tool that
differentiates patients who may proceed to lung resection (classes A or B) from
those who should receive additional cardiac evaluation (classes C or D). This
study aims to describe the ability of the ThRCRI to stratify patients based on
major cardiac complication rates using a large multi-institutional dataset.
METHODS: Patients undergoing lobectomy or pneumonectomy were identified in the
American College of Surgeons National Surgical Quality Improvement Program
dataset from 2005 to 2012. Patients were grouped into 4 risk classes based on a
summary score of preoperative risk factors: ischemic heart disease,
cerebrovascular disease, renal comorbidity, and pneumonectomy. The primary
outcome was the incidence of perioperative major cardiac complication in each of
the 4 risk classes. RESULTS: Of the 4,625 patients identified, the majority
underwent surgery for malignant disease (78%) and had an open procedure (70%).
Among ThRCRI risk factors, 9% of patients had ischemic heart disease, 7% had
cerebrovascular disease, 2% had renal comorbidity, and 6% underwent
pneumonectomy. Incidence of cardiac complication in all patients was 2%.
Incidence of cardiac complication within risk classes A, B, C, and D were 1%, 3%,
9%, and 4%, respectively (p < 0.01). CONCLUSIONS: Using a large multi
institutional dataset, the ThRCRI can differentiate patients at higher risk for
cardiac complication following lung resection (classes C and D) and can be a
useful preoperative instrument. The ThRCRI may allow for identifying patients who
would benefit from additional cardiac evaluation.
PMID- 28499656
TI - Outcome of a Step-Up Treatment Strategy for Chyle Leakage After Esophagectomy.
AB - BACKGROUND: Thoracic chyle leakage is a major complication of esophagectomy. In
this study our treatment strategy for chyle leakage was evaluated and its risk
factors were identified. METHODS: According to the Esophagectomy Complications
Consensus Group recommendations, chyle leakage was classified as follows: I,
enteric dietary modifications; II, total parenteral nutrition (TPN); and III,
interventional or surgical therapy. It was graded as A, less than 1,000 mL per
day; or B, more than 1,000 mL per day. In our protocol, chyle leakage less than
500 mL per day was treated with a low-fat diet; more than 1,000 mL per day, with
TPN, and 500 to 1,000 mL per day, with a low-fat diet or TPN depending on whether
the chyle leakage was increasing or decreasing at diagnosis and the clinical
condition. Surgery was reserved for refractory leakages. RESULTS: In total 371
patients were included. Chyle leakage incidence was 21%, consisting of 51% grade
A and 49% grade B leakage. Chyle leakage severity was associated with length of
stay (grade A, median 17 days versus B, 25 days; p = 0.006). Independent risk
factors were a transthoracic approach (odds ratio 4.8, p = 0.002), neoadjuvant
chemoradiotherapy (odds ratio 2.6, p = 0.002), and preoperative body mass index
(exp(B) 0.92, p = 0.031). Treatment consisted of low-fat diet in 53%, TPN in 37%,
and surgery in 10% of the patients. Low-fat diet and TPN successfully treated 87%
of chyle leaks. Chyle leakages treated by TPN first were significantly more
severe compared with those treated first by low-fat diet, and were significantly
associated with electrolyte deficiencies, increased complication severity, and
length of stay, but not with 90-day mortality. CONCLUSIONS: A step-up treatment
strategy, starting with dietary modifications, solved nearly 90% of chyle leaks
conservatively. A minority of chyle leaks required surgery.
PMID- 28499657
TI - Electrically Assisted Movement Therapy in Chronic Stroke Patients With Severe
Upper Limb Paresis: A Pilot, Single-Blind, Randomized Crossover Study.
AB - OBJECTIVE: To evaluate the effects of electrically assisted movement therapy
(EAMT) in which patients use functional electrical stimulation, modulated by a
custom device controlled through the patient's unaffected hand, to produce or
assist task-specific upper limb movements, which enables them to engage in
intensive goal-oriented training. DESIGN: Randomized, crossover, assessor
blinded, 5-week trial with follow-up at 18 weeks. SETTING: Rehabilitation
university hospital. PARTICIPANTS: Patients with chronic, severe stroke (N=11;
mean age, 47.9y) more than 6 months poststroke (mean time since event, 46.3mo).
INTERVENTIONS: Both EAMT and the control intervention (dose-matched, goal
oriented standard care) consisted of 10 sessions of 90 minutes per day, 5
sessions per week, for 2 weeks. After the first 10 sessions, group allocation was
crossed over, and patients received a 1-week therapy break before receiving the
new treatment. MAIN OUTCOME MEASURES: Fugl-Meyer Motor Assessment for the Upper
Extremity, Wolf Motor Function Test, spasticity, and 28-item Motor Activity Log.
RESULTS: Forty-four individuals were recruited, of whom 11 were eligible and
participated. Five patients received the experimental treatment before standard
care, and 6 received standard care before the experimental treatment. EAMT
produced higher improvements in the Fugl-Meyer scale than standard care (P<.05).
Median improvements were 6.5 Fugl-Meyer points and 1 Fugl-Meyer point after the
experimental treatment and standard care, respectively. The improvement was also
significant in subjective reports of quality of movement and amount of use of the
affected limb during activities of daily living (P<.05). CONCLUSIONS: EAMT
produces a clinically important impairment reduction in stroke patients with
chronic, severe upper limb paresis.
PMID- 28499658
TI - [Radiotherapy volume delineation based on (18F)-fluorodeoxyglucose positron
emission tomography for locally advanced or inoperable oesophageal cancer].
AB - PURPOSE: To study the impact on radiotherapy planning of an automatically
segmented target volume delineation based on (18F)-fluorodeoxy-D-glucose (FDG)
hybrid positron emission tomography-computed tomography (PET-CT) compared to a
manually delineation based on computed tomography (CT) in oesophageal carcinoma
patients. METHODS AND MATERIALS: Fifty-eight patients diagnosed with oesophageal
cancer between September 2009 and November 2014 were included. The majority had
squamous cell carcinoma (84.5 %), and advanced stage (37.9 % were stade IIIA) and
44.8 % had middle oesophageal lesion. Gross tumour volumes were retrospectively
defined based either manually on CT or automatically on coregistered PET/CT
images using three different threshold methods: standard-uptake value (SUV) of
2.5, 40 % of maximum intensity and signal-to-background ratio. Target volumes
were compared in length, volume and using the index of conformality. Radiotherapy
plans to the dose of 50Gy and 66Gy using intensity-modulated radiotherapy were
generated and compared for both data sets. Planification target volume coverage
and doses delivered to organs at risk (heart, lung and spinal cord) were
compared. RESULTS: The gross tumour volume based manually on CT was significantly
longer than that automatically based on signal-to-background ratio (6.4cm versus
5.3cm; P<0.008). Doses to the lungs (V20, Dmean), heart (V40), and spinal cord
(Dmax) were significantly lower on plans using the PTVSBR. The PTVSBR coverage
was statistically better than the PTVCT coverage on both plans. (50Gy: P<0.0004
and 66Gy: P<0.0006). CONCLUSION: The automatic PET segmentation algorithm based
on the signal-to-background ratio method for the delineation of oesophageal
tumours is interesting, and results in better target volume coverage and
decreased dose to organs at risk. This may allow dose escalation up to 66Gy to
the gross tumour volume.
PMID- 28499660
TI - Stereotactic radiation therapy of brain metastases from colorectal cancer: A
single institution cohort.
AB - PURPOSE: The brain remains an uncommon site of colorectal cancer metastases. Due
to the improvement of overall colorectal cancer patient survival, the incidence
of brain metastases will likely rise. We report the efficacy and safety of
hypofractionnated stereotactic radiation therapy and stereotactic radiosurgery,
and its role in colorectal cancer brain metastasis management. METHODS AND
MATERIAL: Between June 2010 and December 2014, fifteen consecutive patients
received hypofractionnated stereotactic radiation therapy or stereotactic
radiosurgery as first local therapy or following surgical removal for colorectal
cancer brain metastases. The primary endpoint was overall survival. Secondary
endpoints were brain progression free survival, in field control rates and
safety. RESULTS: Median follow-up was 41 months (95% confidence interval [CI]:
[8.9-73.1 months]), median overall survival was 8 months (95% CI [4.7-11.3
months]), and median brain progression-free survival was 5 months (95% CI [3.9
6.1 months]). Five in field recurrences were observed, which makes a control rate
per metastases at 6 and 12 months of 77.8% (95% CI [74.34%-81.26%]), 51.9% (95%
CI [44.21%-59.59%]) respectively. Over the 19 treatment sequences, five in field
recurences were observed: 6, 12 and 18 months control rate per treatment sequence
were 93.3% (95% CI [90.42%-96.18%]), 68.1% (95% CI [62.03%-74.17%]) and 45.4%
(95% CI [36.14%-54.66%]) respectively. Immediate tolerance was good with no
toxicity grade III or more. Long-term toxicity included two radionecrosis among
which, one was symptomatic. DISCUSSION: The results of this retrospective
analysis suggest that hypofractionnated stereotactic radiation therapy and
stereotactic radiosurgery are effective and safe treatment modalities for single
and multiple small brain metastases from colorectal cancer. However, results need
to be confirmed by multicenter, collected data.
PMID- 28499659
TI - [Spinal stereotactic body radiotherapy: French assessment in 2016].
AB - PURPOSE: Stereotactic body radiotherapy to vertebral column remains uncommon
practice and only relevant in selected group of patients. The main objective of
the study was to describe the current state of medical practices of stereotactic
body radiotherapy to vertebral column in France in 2016 and to assess the
diversity of practices to identify areas for improvement and establish a common
database set for this technique. MATERIALS AND METHODS: A questionnaire was
written with contribution of a medical physicist, a radiation oncologist, an
information technologist and a radiotherapy resident. The questionnaire was
distributed online to a radiation oncologists and a medical physicists partner of
selected French radiotherapy specialized centres that provide stereotactic body
radiotherapy to vertebral metastasis from April to June 2016. The questionnaire
surveyed the following topics: patients' selection, simulation, targeted volume
and organs at risk delineation, prescription, dosimetric implementation and image
guidance. RESULTS: A total of 31 centres were surveyed. Seventy eight per cent of
centres (n=21) completed the questionnaire. The "ideal" patient for spine
stereotactic radiotherapy according to these institutions has a good performance
status, a long life expectancy, controlled primary tumour with oligometastatic
spread. The most prescribed protocol was 30Gy in three fractions. For clinical
target volume delineation, about two thirds of centres used the International
Spine Radiosurgery Consortium (ISRC) recommendations (Noel G et al.,2006).
CONCLUSION: This study identified some consistency of practices in some aspects
despite the lack of consensus guidelines. Nevertheless, further studies are
needed to establish consensus of planning and treatment.
PMID- 28499661
TI - Second malignancies after permanent implant prostate cancer brachytherapy: A
single-institution study of 675 patients treated between 1999 and 2003.
AB - PURPOSE: To analyse the rate of secondary malignancies observed in a series of
675 prostate cancer patients who underwent a permanent implant brachytherapy
between 1999 and 2003, and to compare the incidence with the expected rate in a
matched general French population. MATERIAL AND METHODS: The cohort included low
risk patients and a selection of "favourable-intermediate" risk patients. All
patients were homogeneously treated using an intraoperative dynamic planning
prostate brachytherapy technique, with loose 125-iodine seeds and a prescription
dose of 145Gy. The mean follow-up was 132 months. RESULTS: The 10-year overall
survival for the entire cohort was 92% (95% confidence interval [CI]: 90-94). The
10-year relapse-free survival rate was 82% (95% CI: 79-85). Overall, 61 second
cancers were registered. When comparing with a matched general French population,
the standard incidence ratio (SIR) for bladder cancer was 1.02 (95% CI: 0.46
1.93). For colorectal cancer, the SIR was 0.45 (95% CI: 0.19-0.89). For lung
cancer, the SIR was 0.38 (95% CI: 0.17-0.76). The SIR for all cancers was 0.61
(95% CI: 0.47-0.79). When excluding secondary colorectal and lung cancers (both
with low SIRs in this series), the SIR for all cancers was 1.06 (95% CI: 0.77
1.29). CONCLUSION: With a mean follow-up of more than 11 years, this series does
not detect any excess risk of second cancers associated with permanent implant
prostate brachytherapy. However, due to power limitation, a small increase in the
risk of secondary malignancies cannot be totally ruled out.
PMID- 28499662
TI - [Acute toxicity of breast cancer irradiation with modulated intensity by
tomotherapy(r)].
AB - PURPOSE: Helical radiation intensity modulated by tomotherapy improves dose
distribution to complex and large volumes. The aim of the study was to assess
acute toxicity of this technique during breast cancer irradiation after
conserving surgery or mastectomy. PATIENTS AND METHODS: Cutaneous toxicities,
lung and oesophageal side effects, and breast lymphedema were retrospectively
collected according to the Common Terminology Criteria for Adverse Events Version
4.0 (CTCAE v4.0) in 292 patients treated for a breast cancer by tomotherapy
between May 2010 and December 2014. After conservative surgery, the dose
administered to breast volume and the tumour bed was respectively 52.2Gy and
63.8Gy in 29 fractions. After mastectomy, the dose was 50Gy in 25 fractions.
Univariate and multivariate analyses were performed to highlight risk factors for
dermatitis and breast oedema. RESULTS: The rate of dermatitis grade 2 and 3 were
22.9% and 1.7% respectively. In univariate analysis, factors associated with
acute radiation dermatitis were breast volume (P=0.002), body mass index (BMI)
(P<0.0001), the use of chest compression mask (net) (P=0.005) and the
localization of the irradiation (P <0.0001). In multivariate analysis, BMI
greater than 25kg/m2 (odds ratio [OR]: 3.61, 95% confidence interval [CI]: [1.93
6.74], P<0.0001), the use of a chest mask (OR 2.01, 95% CI [1.06-3.79] P=0.0328)
and irradiation after conservative treatment increase the risk of acute radiation
dermatitis (mastectomy: OR 0.64, 95% CI [0.04-0.43]; mastectomy with immediate
reconstruction with prosthesis: OR 0.13 95% CI [0.10-0.38] P=0.0003). The
incidence of breast oedema grade 2 or above was 19.5%, in univariate analysis,
there was a correlation with BMI (P=0.003) and smoking (P=0.009). In multivariate
analysis, smoking and BMI greater than 25kg/m2 increased the risk of breast
oedema (OR 2.47, respectively [95% CI 1.22-5.01] P=0.012 and OR 2.37 [95% CI 1.22
4.59] P=0.01). The rate of radiation pneumonitis of grade 2 or above was 1.4%.
Among the patients, 19.9% had esophagitis grade 1 or 2. CONCLUSION: The helical
irradiation intensity modulation tomotherapy is a well-tolerated treatment for
breast cancer that reduces the high radiation doses to organs at risk.
PMID- 28499663
TI - Htr2c Splice Variants and 5HT2CR-Mediated Appetite.
AB - Serotonin 2C receptor (5HT2CR) exists as different isoforms as a result of
alternate splicing. A truncated variant (5HT2CR-trunc) has no canonical receptor
function and yet shows robust expression levels throughout the brain. Recent work
has demonstrated the biochemical role of this isoform and how altering levels of
5HT2CR-trunc leads to changes in behaviour.
PMID- 28499664
TI - STEMI with fluctuating closing of LAD and Cx: Do not concentrate on the finger.
AB - Case report of the male with an anterior STEMI to whom a primary PCI is
performed. The angiogram shows a fluctuating close of the LAD and Cx than when an
OCT is performed does not clearly see any pathological findings but when the IVUS
is performed, it is clearly seen as a coronary haematoma at the LM, LAD and Cx.
Stent at the LM-LAD and proximal Cx are implanted with final good result. After
exchanging the guiding catheter for a diagnostic catheter to visualize the RCA,
there is an aortic flap; the coronary haematoma was coming from an ascending
aortic dissection. The CT confirms the type A aortic dissection and the patient
is sent to urgent surgery where it seems that the point of intimal disruption is
close to brachiocephalic trunk; a supracommissural ascending aortic replacement
is performed. After several complications the patient did well and he is alive.
Although the patient got the right approach, as we focused on the coronary
arteries we did not realized there was an aortic dissection until the end of the
procedure.
PMID- 28499665
TI - Persistent T-wave inversion predicts myocardial damage after ST-elevation
myocardial infarction.
AB - BACKGROUND: Persistent T-wave inversion (PTI) after ST-elevation myocardial
infarction (STEMI) is associated with worse clinical outcome; however, the
underlying mechanism between PTI and poor prognosis is incompletely understood.
We sought to investigate the relationship between PTI and myocardial damage
assessed by cardiac magnetic resonance (CMR) following STEMI. METHODS: In this
prospective observational study, we included 142 consecutive revascularized STEMI
patients. Electrocardiography to determine the presence and amplitude of PTI and
pathological Q-waves was conducted 4months after infarction. CMR was performed
within 1week after infarction and at 4months follow-up to evaluate infarct
characteristics and myocardial function. RESULTS: Patients with PTI (n=103, 73%)
showed a larger acute (21[11-29] vs. 6[1-13]%; p<0.001) and chronic infarct size
(IS) (14[8-19] vs. 3[1-8]%; p<0.001) and more frequently microvascular
obstruction (59 vs. 33%; p=0.02). The association between PTI and chronic IS
remained significant (odds ratio: 9.02, 95%CI 3.49-23.35; p<0.001) after
adjustment for pathological Q-wave and other IS estimators (high-sensitivity
cardiac troponin T and C-reactive protein, N-terminal pro B-type natriuretic
peptide, culprit vessel, pre-interventional TIMI flow). The value of PTI
amplitude for the prediction of large chronic IS>11% (AUC: 0.84, 95%CI 0.77-0.90)
was significantly higher compared to Q-wave amplitude (AUC: 0.72, 95%CI 0.63
0.80; p=0.009); the combination of PTI with pathological Q-wave (Q-wave/T-wave
score) led to a net reclassification improvement of 0.43 (95% CI 0.29-0.57;
p<0.001) as compared to PTI alone. CONCLUSIONS: PTI following STEMI is
independently and incrementally associated with more extensive myocardial damage
as visualized by CMR. An electrocardiographic score combining PTI with
pathological Q-wave allows for a highly accurate IS estimation post-STEMI.
PMID- 28499666
TI - Long-term survival after off-pump versus on-pump coronary artery bypass graft
surgery. Does completeness of revascularization play a role?
AB - BACKGROUND: We sought to compare the incidence of incomplete revascularization
(IR) and long-term survival (up to 20years) after off-pump (OPCAB) versus on-pump
(ONCAB) coronary artery bypass in a high OPCAB volume centre where OPCAB was
introduced in 1996 and has become the preferred strategy over the years. METHODS
AND RESULTS: From 1996 to 2015 a total of 7,427 OPCAB and 7128 ONCAB procedures
were performed at Bristol Heart Institute, United Kingdom. We obtained 5423
propensity matched pairs for final comparison. Mixed effect Cox model accounting
for clustering due to different surgeon was used to investigate the treatment
effect on mortality. RESULTS: OPCAB was associated with higher rate of incomplete
revascularization 13.3% versus 6.7%; P<0.0001). Mean follow-up time was 7.8+/
4.6year [max 17.3]. At 12years OPCAB was associated with a marginal but
significant +3% increase in overall mortality (67.4%[95%CI 65.8-69.1] vs
64.4%[95%CI 62.7-66.2]; stratified log-rank P=0.03). When compared to ONCAB with
complete revascularization, OPCAB with IR (HR 1.74;95%CI 1.53-1.99; P<0.001) and
ONCAB with IR (HR 1.29; 95%CI 1.06-1.57; P=0.01) but not OPCAB with complete
revascularization (HR 1.02;95%CI 0.94-1.11; P=0.63) were associated with
increased risk of late mortality. CONCLUSION: Despite completeness of
revascularization was achieved in the majority of OPCAB cases, OPCAB remained
associated with a significantly higher rate of incomplete revascularization. This
translated into a marginal but significant reduction in late survival rates after
OPCAB when compared to ONCAB.
PMID- 28499667
TI - Insight into the incidence of acute aortic dissection in the German region of
Berlin and Brandenburg.
AB - BACKGROUND: Stanford acute type A aortic dissection (ATAAD) is a potentially
lethal condition. Epidemiology studies show a statistical incidence in Europe of
approximately 2-16 cases/100,000 inhabitants/year. In Germany, the estimated
incidence (here subsumed under "thoracic aortic dissection" with 4.63
cases/100,000 inhabitants/year) is mainly extracted from medical death
certificates by the German Federal Statistical Office. The prehospital incidence
of ATAAD deaths is largely unknown. Since patients often die in the pre-hospital
setting, the incidence of ATAAD is therefore likely to be higher than current
estimates. MATERIAL AND METHODS: For the period from 2010 to 2014, we
retrospectively analyzed all in-hospital ATAAD data from two of the largest
cardiac surgical centers that treat ATAAD in the Berlin-Brandenburg region. In
addition, autopsy reports of all forensic medicine institutes and of one large
pathological provider in the region were analyzed to identify additional non
hospitalized ATAAD patients. Based on these findings, the regional incidence of
ATAAD was calculated. RESULTS: In addition to in-hospital ATAAD patients (n=405),
we identified additional 145 lethal ATAAD cases among 14,201 autopsy reports. The
total of 550 ATAAD cases led to an estimated incidence of 11.9 cases/100,000
inhabitants/year for the whole Berlin-Brandenburg region. Arterial hypertension,
pre-existing aortic dilatation, and hereditary connective tissue disorder were
found in, respectively, 62.7%, 10%, and 1.8% of patients. CONCLUSION: ATAAD is
more frequent than previously reported. Our results show that when patients who
die outside of cardiac surgery centers are included, the incidence of ATAAD
significantly exceeds the rate reported by the Federal Statistical Office.
PMID- 28499668
TI - A multicenter feasibility study on ultrafiltration via a single peripheral venous
access in acute heart failure with overt fluid overload.
AB - OBJECTIVES: The need for a central venous catheter has limited the widespread use
of ultrafiltration in daily clinical practice for the treatment of acute heart
failure (AHF) with overt fluid overload. We evaluated the feasibility of a new
ultrafiltration device, the CHIARA (Congestive Heart Impairment Advanced Removal
Approach) system, that utilizes a single-lumen cannula (17G, multi-hole) inserted
in a peripheral vein of the arm. METHODS: In this multicenter, prospective,
feasibility study, consecutive ultrafiltration treatments (lasting >=6 hours and
with an ultrafiltration rate >=100ml/h) with the CHIARA device and a single
peripheral venous approach were performed at 6 Italian hospitals. For each
session, we evaluated the performance of the venous access, the ultrafiltrate
volume removed, and the cause of its interruption. RESULTS: One-hundred-three
ultrafiltration sessions were performed in 55 patients with AHF (average 1.9+/
1.7 treatment/patient). The overall median length of ultrafiltration treatment
was 14h (interquartile range 7-21) with removal of 3266+/-3088ml of fluid (183+/
30ml/hour). The treatment was successfully completed in 92 (89%) sessions and in
80% of patients. The mean suction flow rate from the vein was 70+/-20ml/min,
while the mean re-injection flow rate was 98+/-26ml/min. There were no clinically
relevant complications related to the venous access and/or to the anticoagulant
therapy with heparin. CONCLUSIONS: The study demonstrated that the CHIARA system
satisfies clinical applicability and efficacy criteria in the treatment of AHF,
in terms of adequate fluid removal through a single peripheral venous access.
PMID- 28499669
TI - Atorvastatin reduces cardiac and adipose tissue inflammation in rats with
metabolic syndrome.
AB - BACKGROUND: Statins are strong inhibitors of cholesterol biosynthesis and help to
prevent cardiovascular disease. They also exert additional pleiotropic effects
that include an anti-inflammatory action and are independent of cholesterol, but
the molecular mechanisms underlying these additional effects have remained
unclear. We have now examined the effects of atorvastatin on cardiac and adipose
tissue inflammation in DahlS.Z-Leprfa/Leprfa (DS/obese) rats, which we previously
established as a model of metabolic syndrome (MetS). METHODS AND RESULTS:
DS/obese rats were treated with atorvastatin (6 or 20mgkg-1day-1) from 9 to
13weeks of age. Atorvastatin ameliorated cardiac fibrosis, diastolic dysfunction,
oxidative stress, and inflammation as well as adipose tissue inflammation in
these animals at both doses. The high dose of atorvastatin reduced adipocyte
hypertrophy to a greater extent than did the low dose. Atorvastatin inhibited the
up-regulation of peroxisome proliferator-activated receptor gamma gene expression
in adipose tissue as well as decreased the serum adiponectin concentration in
DS/obese rats. It also activated AMP-activated protein kinase (AMPK) as well as
inactivated nuclear factor-kappaB (NF-kappaB) in the heart of these animals. The
down-regulation of AMPK and NF-kappaB activities in adipose tissue of DS/obese
rats was attenuated and further enhanced, respectively, by atorvastatin
treatment. CONCLUSIONS: The present results suggest that the anti-inflammatory
effects of atorvastatin on the heart and adipose tissue are attributable at least
partly to increased AMPK activity and decreased NF-kappaB activity in this rat
model of MetS.
PMID- 28499670
TI - Feasibility and relevance of right parasternal view for assessing severity and
rate of progression of aortic valve stenosis in primary care.
AB - BACKGROUND: Right parasternal view (RPV) is important in assessing the severity
of aortic stenosis (AS). However, the feasibility and relevance of RPV in primary
care is unresolved. Moreover, information regarding the role of RPV in the
evaluation of the hemodynamic progression of AS is lacking. METHODS: Consecutive
patients with peak aortic valve velocity (Vmax) >=2.5m/s were prospectively
enrolled in a primary care echocardiographic laboratory. Aortic Doppler
parameters were evaluated from apical view and RPV. RESULTS: The total number of
enrolled patients was 330 (aged 81+/-11years, 47% female, left ventricular
ejection fraction 64+/-9%). The RPV was feasible in 275 (83%). Vmax and Mean
Gradient were significantly higher and aortic valve area was significantly lower
from RPV as compared to apical view (p<0.0001 for all). Reclassification of
severity towards either moderate or severe AS occurred in 13-26% of patients,
according to different criteria, when evaluated from RPV. Among 108 patients
(40%) undergoing multiple examinations the rate of progression was lower from the
apical approach than from the RPV (0.19+/-0.20m/s/year vs. 0.24+/-0.27m/s/year,
respectively; p=0.03), and was fast (>0.3m/s/year) in 17 patients (16%) from the
apical window vs. 26 patients (24%) from RPV (p<0.0001). CONCLUSION: Implementing
RPV is feasible in primary care and results in a substantial reclassification
rate through the entire spectrum of AS severity. Our data also suggest a
potential role of Doppler interrogation from multiple windows to improve AS
progression assessment.
PMID- 28499671
TI - Tricuspid annuloplasty versus a conservative approach in patients with functional
tricuspid regurgitation undergoing left-sided heart valve surgery: A study-level
meta-analysis.
AB - BACKGROUND: Tricuspid valve (TV) repair at the time of left-sided valve surgery
is indicated in patients with either severe functional tricuspid regurgitation
(TR) or mild-to-moderate TR with coexistent tricuspid annular dilation or right
heart failure. We assessed the benefits of a concomitant TV repair strategy
during left-sided surgical valve interventions, focusing on mortality and
echocardiographic TR-related outcomes. METHODS: A meta-analysis was performed of
studies reporting outcomes of patients who underwent left-sided (mitral and/or
aortic) valve surgery with or without concomitant TV repair. Primary endpoints
were all-cause and cardiac-related mortality; secondary endpoints were the
presence of more-than-moderate TR, TR progression, and TR severity grade. All
endpoints were evaluated at the longest available follow-up. RESULTS: Fifteen
studies were included for a total of 2840 patients. TV repair at the time of left
sided valve surgery was associated with a significantly lower risk of cardiac
related mortality (odds ratio [OR] 0.38; 95% confidence interval [CI]: 0.25-0.58;
p<0.001), with a trend towards a lower risk of all-cause mortality (OR 0.57; 95%
CI: 0.32-1.05; p=0.07) at a mean weighted follow-up of 6years. The presence of
more-than-moderate TR (OR 0.19; 95% CI: 0.12-0.30; p<0.001), TR progression (OR
0.03; 95% CI: 0.01-0.05; p<0.001), and TR grade (standardized mean difference
1.11; 95% CI: -1.57 to -0.65; p<0.001) were significantly lower in the TV repair
group at a mean weighted follow-up of 4.7years. CONCLUSIONS: A concomitant TV
repair strategy during left-sided valve surgery is associated with a reduction in
cardiac-related mortality and improved echocardiographic TR outcomes at follow
up.
PMID- 28499672
TI - Association of elevated pulmonary artery systolic pressure with stroke and
systemic embolic events in patients with hypertrophic cardiomyopathy.
AB - BACKGROUND: Echocardiographically estimated pulmonary artery systolic pressure
(PASP) is a non-invasive widely available method that is used to estimate
pulmonary arterial pressure. Although elevated PASP predicts mortality in
patients with hypertrophic cardiomyopathy (HCM), the relationship between PASP
and embolic events is unclear. This study aimed to determine whether elevated
PASP is associated with stroke and systemic embolic events in a tertiary referral
HCM cohort. METHODS: This study included 374 clinically diagnosed patients with
HCM. PASP was estimated from tricuspid regurgitant jet velocity using the
modified Bernoulli equation. RESULTS: The median (interquartile range) PASP was
33 (28-37) mm Hg, and elevated PASP (>40mmHg) was observed in 66 (17.6%)
patients. Seventeen of the 66 (25.8%) patients with elevated PASP and 24 of the
308 (7.8%) patients without elevated PASP experienced stroke and systemic embolic
events during the 10.3+/-7.4years of follow-up (log-rank P<0.001). Multivariable
analysis showed that age at diagnosis, atrial fibrillation, and PASP >40mmHg
(adjusted hazard ratio, 2.59; 95% confidence interval, 1.31-5.12; P=0.006) were
independently associated with embolic events. CONCLUSIONS: In addition to age and
atrial fibrillation, PASP estimated by Doppler echocardiography could help
embolic risk stratification in patients with HCM.
PMID- 28499673
TI - [How I do... to perform uterine adenomyomectomy].
PMID- 28499674
TI - [Training of residents in amniocentesis: Effectiveness of a craft simulator].
AB - OBJECTIVE: This prospective study aims to assess a low fidelity simulation device
for learning amniocentesis to gynecology-obstetrics residents. METHODS: From 2013
to 2016, gynecology-obstetrics residents of all levels, from the maternity of
Nancy hospital, which have already performed amniocentesis or not, participated
in amniocentesis training on an artisanal simulator. Residents were evaluated on
the amniocentesis simulator according to seven quality criteria. Three scores
were assigned: the first (S1) at the beginning of the first training session, the
second (S2) at the end of the first session after individualized personal
training and the third (S3) two months after the first simulation. RESULTS: A
total of 40 residents were included. The scores obtained by the residents were
3.2+/-1.8 points for S1 versus 6.2+/-0.9 points for S2 (P<0.001). Two months
after, the residents' performances remained significantly improved compared to
the initial assessment with a score (S3) of 5.8+/-1.3 points at S3 (P<0.001).
CONCLUSION: Amniocentesis craft simulator is effective for performance
improvement and allows a persistence of acquired skills two months after the
training. At the time of "never the first time on the patient", it should be part
of the curriculum of gynecology-obstetrics residents in order to guarantee
patients quality care and optimum safety.
PMID- 28499675
TI - Growth and Psychological Development in Postoperative Patients With Anterior
Encephaloceles.
AB - PURPOSE: Anterior encephaloceles are rare malformations that are frequently
associated with other brain anomalies. This study evaluates the growth and
psychological development of children following encephalocele repair. MATERIALS &
METHODS: Growth and psychological assessment was done in 24 children with only
encephalocele (group I); nine children with encephalocele and hydrocephalus
(group II); seven children with encephalocele, hydrocephalus, and secondary
malformations (group III); and 40 apparently healthy control subjects.
Psychological assessment was done by evaluating intelligence and temperament.
RESULTS: Single-stage repair was performed in 38 children, and two underwent
multistage repair. Major postoperative complications were noted in three
individuals. The follow-up period ranged from 12 to 168 months, and during this
time the growth velocity declined significantly among group II and group III
patients when compared with control subjects. After adjusting the body mass index
for age, our data revealed that group III participants had a significantly (P =
0.02) lower body mass index than the control group. Group III also had poor
indices for intelligence quotient (P <= 0.01) and temperament (P <= 0.01). Female
patients had lower temperament indices when compared with unaffected females with
regard to approach withdrawal (P <= 0.01), mood (P = 0.026), and intensity (P =
0.03). Overall, increased disease severity adversely affected the psychological
indices. CONCLUSION: Individuals with anterior encephalocele without associated
intracranial defects had excellent postoperative outcomes in terms of growth and
psychological developments. Hydrocephalus and agenesis of corpus callosum had the
least impact on psychological development. However, the presence of secondary
brain defects led to developmental delays. Gender differences in temperament may
suggest a need for distinct treatment regimens to assess psychosocial well-being
for males and females.
PMID- 28499678
TI - Saving Lives for 35 Years: Sentara Nightingale Looks Forward.
AB - The Nightingale Regional air Ambulance program, operated by Norfolk, VA-based not
for-profit Sentara Healthcare, is marking its 35th year of operation in 2017,
having surpassed 20,000 safe flights. Looking ahead, the program is adding IFR
capabilities, designated landing zones to rendezvous with EMS partners and
clinical training in a simulation lab, and collaborating with cardiac and
neurology services to provide quicker interventions for STEMI and stroke patients
at Sentara Norfolk General Hospital.
PMID- 28499679
TI - Aeromedical Ultrasound: The Evaluation of Point-of-care Ultrasound During
Helicopter Transport.
AB - INTRODUCTION: This study correlated the eFAST findings performed in-flight by the
flight crew with the findings obtained by the trauma team upon initial evaluation
at a level 1 trauma center and with the subsequent CT scans that were performed
or the surgeon's operative note. We hypothesize that aeromedical eFAST
examinations are highly correlated with the trauma teams findings. METHODS: This
prospective, observational study evaluated 190 traumatically injured patients
from June 2014 to December 2015 in Southeast Virginia and Northeast North
Carolina. RESULTS: For 190 trauma patients the Flight Crew POCUS examinations
obtained a Positive Predictive Value (PPV) of 100% and a Negative Predictive
Value (NPV) of 98.3% for the identification of pneumothorax, hemothorax, and free
abdominal fluid, which is equivalent to that of the Trauma Team's POCUS studies
on the same group of patients. DISCUSSION: Because the early recognition of
potentially life-threatening conditions is critical to providing appropriate care
to the traumatically injured patient this study provides solid statistical data
that flight crews can adequately perform and interpret POCUS results as well as
out trauma team colleagues. This study could lead to a reduction of iatrogenic
injuries from unnecessary invasive prehospital procedures, allow for early
initiation of Massive Transfusion Protocols (MTP) prior to the patient's arrival
at the Trauma Center, and potentially develop a change in trauma systems
notification and transportation directly to the operating room. CONCLUSION:
Despite this study developing a very positive outlook on performing aeromedical
POCUS for the evaluation and care of trauma patients additional research will be
required to better understand the potential impact on trauma activation protocols
and activation of in-hospital resources.
PMID- 28499680
TI - A Systematic Review of the Prevalence and Types of Adverse Events in
Interfacility Critical Care Transfers by Paramedics.
AB - OBJECTIVE: The aim of this study was to investigate if paramedics can safely
transfer interfacility critically ill adult patients and to determine the
prevalence and types of adverse events when paramedics lead interfacility
critical care transfers. METHODS: MEDLINE, Web of Science, Embase, and CINAHL
databases were searched from 1990 up to February 2016. Eligibility criteria were
adult patients (16 years and over), interfacility transfer (between two health
care facilities), quantitative or qualitative description of adverse events, and
a paramedic as the primary care provider or the sole health care provider.
RESULTS: Seven publications had paramedics as the sole health care provider
conducting interfacility critical care transfers. All seven studies were
observational studies published in the English language. The study duration
ranged from 14 months to 10 years. The frequency of adverse events seen by
paramedics in interfacility transfers ranges from 5.1% to 18%. CONCLUSION: There
is a gap in literature on the safety and adverse events in interfacility
transfers by paramedics. The prevalence of in-transit adverse events is well
established; however, because the published literature is lacking longitudinal
monitoring of patients and only reporting in-transit events, we believe that
further research in this area might provide the basis of paramedics safety in
interfacility transfers.
PMID- 28499681
TI - Is Nifedipine as a Tocolytic Effective in Facilitating In Utero Transfer?
AB - OBJECTIVE: Previous studies have reported that air medical transfer of women in
preterm labor can be safely accomplished, without preterm birth occurring; in
fact, many women were later discharged without preterm birth occurring. The
purpose of this study was to determine if nifedipine, when used as a tocolytic,
is effective at facilitating in utero transfer of women in preterm labor in the
Top End of the Northern Territory of Australia. METHODS: This was a retrospective
descriptive study over a 3-year period of all women transported in preterm labor
between 23 + 6 to 36 + 6 weeks' gestation of pregnancy (N = 325). RESULTS: The
average gestation period was 32 + 2 weeks. The mean retrieval time was 6 hours.
The mean time of birth from referral was 33 hours. A number of women gave birth
to a preterm newborn in a remote health center (17%). There were 3 in-flight
preterm births, and 49% of women were discharged without a preterm birth
occurring. All women transported by air medical retrieval were admitted to the
tertiary hospital for at least 24 hours. CONCLUSION: In this study, nifedipine
was used successfully to facilitate in utero transfer in many cases. Nearly half
of the women referred were discharged without preterm birth occurring. Findings
compare favorably with other published studies.
PMID- 28499682
TI - An Analysis of the Temperature Change in Warmed Intravenous Fluids During
Administration in Cold Environments.
AB - This nonhuman simulation study was conducted to determine the decrease in
temperature that occurred to 1-L bags of normal saline in a cold environment. The
bags were warmed to 39 degrees C and administered through intravenous (IV) tubing
at a set flow rate while in a cold environment. The goal was to determine if
there was a significant decrease in fluid temperature from the bag to the
catheter site. Three trials were completed at temperatures of 0 degrees C, -7
degrees C, -12 degrees C, and 22 degrees C (control). Each bag of normal saline
was warmed to 39 degrees C using the SoftSack IV Fluid Warmer (Smithworks Med
Inc, Lindale, TX). Fluid was collected and temperatures recorded at 5-minute
intervals. The results showed a statistically significant (P = .003) change in
temperature between the IV bag and the administration site. The most rapid change
occurred within the first 5 minutes. The temperature change was more significant
with colder ambient temperatures, with an average of a 28.7 degrees C difference
at -7 degrees C and -12 degrees C after 30 minutes. It appears that the most
significant heat loss occurs through the IV tubing itself. Therefore, it may be
beneficial to insulate the tubing on a trauma patient receiving warmed IV fluids
in a cold environment to help prevent hypothermia.
PMID- 28499683
TI - Response of Flight Nurses in a Simulated Helicopter Environment.
AB - OBJECTIVE: The purpose of this study was to determine if a helicopter flight
simulator could provide a useful educational platform by creating experiences
similar to those encountered by actual flight nurses. METHODS: Flight nurse (FN)
and non-FN participants completed a simulated emergency scenario in a flight
simulator. Physiologic and psychological stress during the simulation was
measured using heart rate and perceived stress scores. A questionnaire was then
administered to assess the realism of the flight simulator. RESULTS: Subjects
reported that the overall experience in the flight simulator was comparable with
a real helicopter. Sounds, communications, vibrations, and movements in the
simulator most approximated those of a real-life helicopter environment.
Perceived stress levels of all participants increased significantly from 27 (on a
0-100 scale) before simulation to 51 at the peak of the simulation and declined
thereafter to 28 (P < .001). Perceived stress levels of FNs increased
significantly from 25 before simulation to 54 at the peak of the simulation and
declined thereafter to 30 (P < .001). Perceived stress levels of non-FNs
increased significantly from 31 before simulation to 49 at the peak of the
simulation and declined thereafter to 25 (P < .001). There were no significant
differences in perceived stress levels between FNs and non-FNs before (P = .58),
during (P = .63), or after (P = .55) simulation. FNs' heart rates increased
significantly from 77 before simulation to 100 at the peak of the simulation and
declined thereafter to 72 (P < .001). CONCLUSION: The results of this study
suggest that simulation of a critical care scenario in a high-fidelity helicopter
flight simulator can provide a realistic helicopter transport experience and
create physiologic and psychological stress for participants.
PMID- 28499684
TI - Flying Lessons for Clinicians: Developing System 2 Practice.
AB - There is a long history of adopting lessons learned from aviation to improve
health care practice. Two of the major practices that have successfully
transferred include using a checklist and simulation. Training and simulation
technology is currently underdeveloped for nurses and health care providers
entering critical care transport. This article describes a pedagogical approach
adopted from aviation to develop a new simulation platform and program of
research to develop the science of critical care transport nursing education.
PMID- 28499685
TI - Ultrasound in the Royal Danish Air Force Search and Rescue Helicopter: 2 Case
Reports.
PMID- 28499686
TI - An Unusual Case of Shortness of Breath.
PMID- 28499688
TI - In Memoriam.
PMID- 28499687
TI - Erratum to 'Air Medical Evacuations From the German North Sea Wind Farm Bard
Offshore 1: Traumatic Injuries, Acute Diseases, and Rescue Process Times (2011
2013)' [Air Medical Journal 35 (2016) 216-226].
PMID- 28499689
TI - An 89-Year-Old Man Hanging in a Remote Location.
PMID- 28499690
TI - Weaning.
PMID- 28499691
TI - Good People Don't Smoke Marijuana.
PMID- 28499692
TI - Genital discomfort: yeast, trichomonas and bacterial vaginosis are only the tip
of the iceberg.
PMID- 28499693
TI - A case report of mysterious bleeding.
PMID- 28499694
TI - Effectiveness and safety of community-based treatment with sofosbuvir plus
ribavirin for elderly patients with genotype 2 chronic hepatitis C.
AB - BACKGROUND: The aim of this study was to clarify the effectiveness and safety of
sofosbuvir/ribavirin therapy for elderly patients with genotype 2-infected
chronic hepatitis C (CHC) in Japan. METHODS: A multicenter, retrospective study
evaluated the effectiveness and safety of sofosbuvir/ribavirin based on real
world clinical data. RESULTS: The subjects consisted of 270 patients, 47.0% of
whom were aged >=65 years. The sustained virological response rates in patients
aged <65 and >=65 years were 98.6% and 95.3%, respectively. Hemoglobin levels
decreased during treatment due to ribavirin-related hemolysis, and were
significantly lower in patients aged >=65 years than those aged <65 years at all
time-points. A reduction in ribavirin dose was necessary in 31.0% (26/84) of
patients with hemoglobin levels <13.0g/dL and in 70.7% (39/127) of those aged >65
years. Although the most frequent adverse event was anemia, no patients
discontinued the use of either ribavirin or sofosbuvir. The incidence of
ribavirin-related anemia in patients aged >=65 years was 34.6% and significantly
higher compared with that in patients aged <65 years (2.8%). CONCLUSIONS:
Treatment with sofosbuvir/ribavirin for genotype 2-infected CHC was effective and
safe even for elderly patients, although the incidence of adverse events
including ribavirin-related anemia was relatively high.
PMID- 28499695
TI - Dapagliflozin modulates glucagon secretion in an SGLT2-independent manner in
murine alpha cells.
AB - AIM: SGLT2 inhibitors reduce renal glucose uptake through an insulin-independent
mechanism. They also increase glucagon concentration, although the extent to
which this is due to a direct effect on pancreatic alpha cells remains unclear.
METHODS: In the present work, alphaTC1 cells treated with the SGLT2 inhibitor
dapagliflozin (Dapa) were analyzed for glucose transporters, molecular mediators
of hormone secretion, glucagon and GLP-1 release, and the effects of
somatostatin. Data were validated in murine and human pancreatic islets. RESULTS:
SLC5A2 (the SGLT2-encoding gene) was nearly undetectable in alphaTC1 cells, not
even by a digital PCR technique using different probes. In contrast, SLC5A1 (the
SGLT1-encoding gene) was constitutively abundant in alphaTC1 cells and in islets,
and increased with Dapa. This was associated with greater glucagon release,
preceded by increased expression of preproglucagon and HNF4alpha. Looking at the
candidate intracellular signalling pathway, reduced PASK and increased AMPK
alpha2 expression were also detected. GLUT1 and GLUT2, as well as regulators of
glucagon release and alpha-cell phenotype (chromogranin A, paired box 6,
proprotein convertase 1/2, synaptophysin), were unaffected by Dapa, as were GLP-1
receptor expression and GLP-1 release. Low glucose did not influence the
stimulatory effect of Dapa on glucagon release, but was instead almost fully
reverted by SLC5A1 silencing. When the effect of Dapa on AMPK and PASK, emerging
regulators of lipid and glucose metabolism, was tested, upregulated AMPK-alpha2
appeared to be involved in molecular signalling. CONCLUSION: Our study has shown
that, in alphaTC1 cells, Dapa acutely upregulates SGLT1 expression and increases
glucagon release through an SGLT1-dependent mechanism, with SGLT2 expression
virtually undetectable. These results suggest the involvement of SGLT1 in
modulating glucagon increases following SGLT2 inhibition.
PMID- 28499697
TI - Assessment of dietary compliance in celiac children using a standardized dietary
interview.
AB - BACKGROUND & AIMS: Compliance to a gluten free diet (GFD) in celiac disease (CD)
is ideally assessed by dietary interviews, albeit time-consuming. Short dietary
questionnaires have been developed for adults but not for children. Primary aim
was to compare GFD compliance in celiac children, measured by a short dietary
questionnaire against a dietary interview. Secondary aims were correlation
between both questionnaires and celiac antibodies and identifying variables
predicting noncompliance. METHODS: Between 2012 and 2014, participants in the E
health CoelKids study, completed a short dietary questionnaire and standardized
dietary interview together with measurement of anti-tissue transglutaminase
antibodies (TG2A). Results of the questionnaires were assigned under similar
categories. Factors possibly influencing dietary compliance were recorded. Where
appropriate, Pearson's Chi-square test for trend, unpaired t-test, Cohen's kappa
and one-way ANOVA were used. RESULTS: 151 of 165 participating patients were
studied, 66% were female. Mean age was 11.3 years (2-26, SD 5.4), mean age at CD
diagnosis was 4.9 years (1-23, SD 4.0). The short questionnaire and dietary
interview correlated poorly, detecting problems in dietary adherence in 14% and
52% of the patients, respectively (Cohen's kappa 0.034). Only the short
questionnaire correlated with TG2A (p = 0.003). Only older age was associated
with noncompliance, the mean age of completely nonadherent, adherent but
committing errors, and strictly adherent patients were 15.5, 11.5 and 10.1 years,
respectively (p < 0.001). CONCLUSIONS: Compared to the dietary interview, short
dietary questionnaires and TG2A serology failed to detect dietary transgressions
in CD children, wherein adolescents were shown to be at highest risk.
PMID- 28499696
TI - Fenofibrate decreases plasma ceramide in type 2 diabetes patients: A novel marker
of CVD?
AB - AIM: The benefit of the lipid-lowering drug fenofibrate on cardiovascular
outcomes is controversial. Our aim was to find new circulating markers to
identify those patients most likely to benefit from fenofibrate prescription.
METHODS: Analyses were conducted of plasma samples collected from 102 patients
with type 2 diabetes, enrolled in the FIELD trial, before and after fenofibrate
treatment (200mg/day). Non-targeted and targeted lipid analyses and
apolipoprotein measurements were made using mass spectrometry methods. RESULTS:
Lipidomics revealed a global decrease in ceramide after fenofibrate treatment
confirmed by quantitative analysis (-18.2%, P<0.001). These changes were strongly
associated with those found for plasma sphingomyelin (r=0.80, P<0.001) and, to a
lesser extent, for sphingosine-1-phosphate (r=0.34, P<0.001). Ceramide levels
decreased in 73.5% of patients. In addition to the expected lipid changes
(decreases in triglycerides, total cholesterol and LDL cholesterol, and increase
in HDL cholesterol), fenofibrate also lowered plasma apoC-II (-11.1%, P<0.01),
apoC-III (-24.6%; P<0.001), apoB100 (-27.0%, P<0.01) and sphingomyelinase (-7.6%,
P<0.001), and increased plasma apoA-II (22.4%, P<0.001) as well as adiponectin
(11.4%, P<0.001). No significant association was found between ceramide decrease
and these modulations except for total cholesterol (r=0.20, P=0.047) and HDL
protein components. At baseline, only elevated sphingolipid levels were
significantly associated with ceramide reduction after fenofibrate treatment.
CONCLUSION: Fenofibrate lowers plasma ceramide independently of the usual lipid
parameters. As ceramide is a strong marker of atherosclerosis, our study
underpins the need to further evaluate its contribution to cardiovascular events
in fenofibrate-treated patients.
PMID- 28499698
TI - Dental microwear and Pliocene paleocommunity ecology of bovids, primates,
rodents, and suids at Kanapoi.
AB - Reconstructions of habitat at sites like Kanapoi are key to understanding the
environmental circumstances in which hominins evolved during the early Pliocene.
While Australopithecus anamensis shows evidence of terrestrial bipedality
traditionally associated with a more open setting, its enamel has low delta13C
values consistent with consumption of C3 foods, which predominate in wooded areas
of tropical Africa. Habitat proxies, ranging from paleosols and their carbonates
to associated herbivore fauna and their carbon isotope ratios, suggest a
heterogeneous setting with both grass and woody plant components, though the
proportions of each have been difficult to pin down. Here we bring dental
microwear texture analysis of herbivorous fauna to bear on the issue. We present
texture data for fossil bovids, primates, rodents, and suids (n = 107 individuals
in total) from the hominin bearing deposits at Kanapoi, and interpret these in
the light of closely related extant mammals with known differences in diet. The
Kanapoi bovid results, for example, are similar to those for extant variable
grazers or graze-browse intermediate taxa. The Kanapoi suid data vary by taxon,
with one similar to the pattern of extant grazers and the other more closely
resembling mixed feeders. The Kanapoi primates and rodents are more difficult to
associate with a specific environment, though it seems that grass was likely a
component in the diets of both. All taxa evince microwear texture patterns
consistent with a mosaic of discrete microhabitats or a heterogeneous setting
including both tree and grass components.
PMID- 28499699
TI - Malaria Vector Control Still Matters despite Insecticide Resistance.
AB - Mosquito vectors' resistance to insecticides is usually considered a major threat
to the recent progresses in malaria control. However, studies measuring the
impact of interventions and insecticide resistance reveal inconsistencies when
using entomological versus epidemiological indices. First, evaluation tests that
do not reflect the susceptibility of mosquitoes when they are infectious may
underestimate insecticide efficacy. Moreover, interactions between insecticide
resistance and vectorial capacity reveal nonintuitive outcomes of interventions.
Therefore, considering ecological interactions between vector, parasite, and
environment highlights that the impact of insecticide resistance on the malaria
burden is not straightforward and we suggest that vector control still matters
despite insecticide resistance.
PMID- 28499700
TI - Imatinib mesylate- and dasatinib-induced eosinophilia in a patient with chronic
myelocytic leukemia.
PMID- 28499701
TI - Should We Stop Saying 'Glia' and 'Neuroinflammation'?
AB - Central nervous system (CNS) therapeutics based on the theoretical framework of
neuroinflammation have only barely succeeded. We argue that a problem may be the
wrong use of the term 'neuroinflammation' as a distinct nosological entity when,
based on recent evidence, it may not explain CNS disease pathology. Indeed, the
terms 'neuroinflammation' and 'glia' could be obsolete. First, unbiased molecular
profiling of CNS cell populations and individual cells reveals striking
phenotypic heterogeneity in health and disease. Second, astrocytes, microglia,
oligodendrocytes, and NG2 cells may contribute to higher-brain functions by
performing actions beyond housekeeping. We propose that CNS diseases be viewed as
failed circuits caused in part by disease-specific dysfunction of cells
traditionally called 'glia', and hence, favor therapies promoting their
functional recovery.
PMID- 28499702
TI - Prespermatogenesis and early spermatogenesis in frogs.
AB - Spermatogenesis in frogs was for the first time divided into two phases:
prespermatogenesis, when gonocytes proliferate in developing tadpole testes, and
active spermatogenesis when spermatogonial stem cells (i.e. descendants of
gonocytes), either self-renew or enter into meiotic cycles within cysts formed by
Sertoli cells. We argue that amphibian larval gonocytes are homologues to
mammalian gonocytes, whereas spermatogonial stem cells (SSCs) in adult frogs are
homologous to mammalian single spermatogonia (As). Gonocytes constitute sex
cords, i.e. the precursors of seminiferous tubules; they are bigger than SSCs and
differ in morphology and ultrastructure. The nuclear envelope in gonocytes formed
deep finger-like invaginations absent in SSCs. All stages of male germ cells
contained lipid droplets, which were surrounded by glycogen in SSCs, but not in
gonocytes. Mitochondria in gonocytes had enlarged edges of cristae, and in SSCs
also lamellar mitochondria appeared. Minimal duration of prespermatogenesis was
46days after gonadal sex differentiation, but usually it lasted longer. SSCs give
rise to secondary spermatogonia (equal to mammalian A, In, and B). Their lowest
number inside a cyst was eight and this indicated the minimal number of cell
cycles (three) of secondary spermatogonia necessary to enter meiosis. We sorted
them according to the number of cell cycles (from 8 to 256 cells). This number is
similar to that recorded for mammals as the result of a single As proliferation.
The number of secondary spermatogonia correlates with the volume of a cyst. The
general conclusion is that spermatogenesis in amphibians and mammals follows
basically the same scheme.
PMID- 28499704
TI - Displaced Endoscopic Ultrasound-Guided Gastroenterostomy Stent Rescued With
Natural Orifice Transluminal Endoscopic Surgery.
PMID- 28499703
TI - miR-375 Regulates Invasion-Related Proteins Vimentin and L-Plastin.
AB - Invasion is a hallmark of advanced head and neck squamous cell carcinoma (HNSCC).
We previously determined that low relative miR-375 expression was associated with
poor patient prognosis. HNSCC cells with increased miR-375 expression have lower
invasive properties and impaired invadopodium activity. Using stable isotope
labeling with amino acids in cell culture and reverse-phase liquid chromatography
mass spectrometry, we assessed the impact of miR-375 expression on protein levels
in UM-SCC-1 cells. Increased miR-375 expression was associated with down
regulation of proteins involved in cellular assembly and organization, death and
survival, and movement. Two invasion-associated proteins, vimentin and L-plastin,
were strongly down-regulated by miR-375. Luciferase reporter assays demonstrated
that high miR-375 expression reduced vimentin promoter activity, suggesting that
vimentin is an indirect target of miR-375. Runt-related transcription factor 1
(RUNX1) is a potential miR-375 direct target, and its knockdown reduced vimentin
and L-plastin expression. Data in The Cancer Genome Atlas HNSCC database showed a
significant inverse correlation between miR-375 expression and RUNX1, vimentin,
and L-plastin RNA expression. These clinical correlations validate our in vitro
model findings and support a mechanism in which miR-375 suppresses RUNX1 levels,
resulting in reduced vimentin and L-plastin expression. Furthermore, knockdown of
RUNX1, L-plastin, and vimentin resulted in significant reductions in cell
invasion in vitro, indicating the functional significance of miR-375 regulation
of specific proteins involved in HNSCC invasion.
PMID- 28499706
TI - Pseudophakic Macular Edema in Primary Open-Angle Glaucoma: A Prospective Study
Using Spectral-Domain Optical Coherence Tomography.
AB - PURPOSE: To determine the incidence of and risk factors for pseudophakic macular
edema (PME) after uncomplicated cataract surgery in primary open-angle glaucoma
(POAG) using spectral-domain optical coherence tomography (SDOCT). DESIGN: Cohort
study. METHODS: Macular retinal thickness was evaluated using SDOCT at 1 week
before surgery and at 1, 3, 6, and 12 months postoperatively, in 70 POAG and 68
control eyes. Forty-three healthy subjects without impaired vision or cystoid PME
were recruited separately as pilot samples to define significant PME. Significant
PME was defined as an increase in the average thickness exceeding the mean + 3
standard deviations of the increase shown in the pilot samples. RESULTS:
Significant PME (increase in the foveal 3-mm zone thickness of >19.5 MUm) was
observed in 31 (44%) eyes with POAG and in 14 (21%) control eyes (P = .003). The
extent of PME was maximal at 3 months postoperatively and decreased gradually
until 12 months. Regression tree analysis revealed that the risk of PME was the
greatest in the POAG group using prostaglandin analogue (PGA) (odds ratio [OR] =
5.51), followed by POAG not using PGA (OR = 1.70), and control group (OR = 1.0).
Risk factors for PME were younger age in all groups (OR = 1.07), systemic
hypertension in PGA users (OR = 6.42), higher untreated IOP in PGA nonusers (OR =
1.09) and male sex (OR = 14.06) and diabetes mellitus (OR = 16.71) in the control
group. CONCLUSIONS: The incidence of PME as observed by SDOCT was higher than
previously reported after uncomplicated cataract surgery. Eyes with POAG were at
greater risk for PME, which was mainly associated with perioperative PGA use.
PMID- 28499705
TI - Measurement and Reproducibility of Preserved Ellipsoid Zone Area and Preserved
Retinal Pigment Epithelium Area in Eyes With Choroideremia.
AB - PURPOSE: To identify valid and reproducible methods for quantifying anatomic
outcome measures for eyes with choroideremia (CHM) in clinical trials. DESIGN:
Reliability analysis study. METHODS: In this multicenter study, patients with
confirmed genetic diagnosis of CHM were enrolled. All cases underwent spectral
domain optical coherence tomography (SDOCT) and fundus autofluorescence (FAF)
imaging. Two graders independently delineated boundaries of preserved
autofluorescence (PAF) and preserved ellipsoid zone (EZ) on FAF and OCT images,
respectively. The results of the 2 independent gradings of both FAF and OCT
images were compared to assess the reproducibility of the grading methods.
RESULTS: A total of 148 eyes from 75 cases were included. In 21% of eyes PAF and
in 43% of eyes preserved EZ had extended beyond the image capture area. After
exclusion of these eyes and low-quality images, 114 FAF and 77 OCT images were
graded. The mean PAF areas from 2 independent gradings were 3.720 +/- 3.340 mm2
and 3.692 +/- 3.253 mm2, respectively. Intraclass correlation coefficient (ICC)
for these gradings was 0.996. The mean preserved EZ areas from 2 independent
gradings were 2.746 +/- 2.319 mm2 and 2.858 +/- 2.446 mm2, respectively. ICC for
these gradings was 0.991. CONCLUSIONS: Quantifying preserved retinal pigment
epithelium and EZ areas on FAF and OCT images, respectively, in CHM patients is
highly reproducible. These variables would be potential anatomic outcome measures
for CHM clinical trials and could be studied and tracked longitudinally in
choroideremia.
PMID- 28499707
TI - Lower Laser Energy Levels Lead to Better Visual Recovery After Small-Incision
Lenticule Extraction: Prospective Randomized Clinical Trial.
AB - PURPOSE: To determine the effect of lowering laser energy on clinical outcomes in
small-incision lenticule extraction (SMILE). DESIGN: Prospective randomized
clinical trial. METHODS: A total of 151 patients (151 eyes) with moderate myopia
scheduled for SMILE were included: 58 eyes received SMILE with low energy (100,
105, and 110 nJ; L-SMILE group) and 93 with conventional energy (115-150 nJ; C
SMILE group). Patients received complete ophthalmic examinations preoperatively
and over 3 months postoperatively. RESULTS: Uncorrected distance visual acuity
(logMAR UDVA) 1 day and 1 week postoperatively was significantly better in L
SMILE than in C-SMILE (P < .001 and P = .005, respectively). There was no
significant difference between the groups at 1 and 3 months. L-SMILE induced
significantly fewer corneal aberrations compared with C-SMILE at 1 week and 1
month postoperatively (both P < .01), but there were no significant differences
at 3 months. Though there was no difference in logMAR UDVA over the postoperative
period between the 100, 105, and 110 nJ subgroups, there was a significant
difference in logMAR UDVA on postoperative day 1 between L-SMILE and each
subgroup in which an energy level of 115 nJ or higher was used. Furthermore,
logMAR UDVA on postoperative day 1 showed a significant correlation with laser
energy (r = 0.451, P < .001) and multiple linear regression analysis revealed
that energy level was the only independent factor associated with logMAR UDVA on
postoperative day 1 (P < .001). CONCLUSIONS: SMILE using femtosecond energy of
less than 115 nJ facilitates better visual acuity with less induction of corneal
aberrations in the early postoperative period.
PMID- 28499708
TI - Incidence of Intermediate-stage Age-related Macular Degeneration in Patients With
Acquired Immunodeficiency Syndrome.
AB - PURPOSE: To evaluate the incidence of intermediate-stage age-related macular
degeneration (AMD) in patients with acquired immunodeficiency syndrome (AIDS).
DESIGN: Cohort study. METHODS: Patients enrolled in the Longitudinal Study of the
Ocular Complications of AIDS (LSOCA) underwent 5- and 10-year follow-up retinal
photographs. Intermediate-stage AMD (AREDS stage 3) was determined from these
photographs by graders at a centralized Reading Center, using the Age-Related Eye
Disease Study-2 grading system. The incidence of AMD in LSOCA was compared with
that in the Multi-Ethnic Study of Atherosclerosis (MESA), a Human
Immunodeficiency Virus (HIV)-uninfected cohort, which used a similar photographic
methodology. RESULTS: The incidence of AMD in LSOCA was 0.65/100 person-years
(PY). In a multivariate analysis the only significant risk factor for AMD in
LSOCA was smoking; the relative risk vs never-smokers was 3.4 for former smokers
(95% confidence interval [CI] 1.3, 9.5; P = .02) and 3.3 for current smokers (95%
CI 1.1, 9.7; P = .03). Compared with the MESA cohort, the race/ethnicity- and sex
adjusted risk of AMD in LSOCA was 1.75 (95% CI 1.16, 2.64; P = .008), despite the
fact that the mean age of the MESA cohort was 17 years greater than the LSOCA
cohort (61 +/- 9 years vs 44 +/- 8 years). CONCLUSIONS: Patients with AIDS have a
1.75-fold increased race- and sex-adjusted incidence of intermediate-stage AMD
compared with that found in an HIV-uninfected cohort. This increased incidence is
consistent with the increased incidence of other age-related diseases in
antiretroviral-treated, immune-restored, HIV-infected persons when compared with
HIV-uninfected persons.
PMID- 28499709
TI - Mortality in dialysis patients with cinacalcet use: A large observational
registry study.
AB - BACKGROUND: Secondary hyperparathyroidism (sHPT) is associated with higher
mortality in dialysis patients. The calcimimetic cinacalcet reduces intact
parathyroid hormone (iPTH) in dialysis patients. The randomized controlled EVOLVE
trial failed to unequivocally prove survival advantage of cinacalcet in dialysis
patients. However, recent post hoc analyses suggested a benefit in subgroups of
dialysis patients. Large observational cohort studies may represent an option to
better determine such subgroups. METHODS: Data from the nationwide Austrian
registry of dialysis patients between January 2004 and December 2009 were
analyzed with follow-up until December 2010. All-cause and cardiovascular
mortality analyses were performed using the Kaplan-Meier and Cox proportional
hazards regression. To reduce confounding effects a propensity score (PS) based
method (matching by stratification) was used for group comparison. RESULTS: The
cohort included 7983 dialysis patients, 1572 (19.7%) were prescribed cinacalcet.
During a median follow-up of 2.7years, 3574 (44.8%) patients died, including 1342
(16.8%) deaths from cardiovascular causes. Survival analyses in the PS-matched
study population (n=6109) showed lower all-cause mortality for cinacalcet-treated
as compared to untreated patients only in subsets characterized by younger age,
low prevalence of diabetes, iPTH levels between 300 and 599pg/mL, concomitant
therapy with vitamin D and phosphate binders. CONCLUSIONS: Our data suggest that
a subgroup of dialysis patients, namely those with moderate sHPT, younger age and
without diabetes benefit from cinacalcet with reduced overall and cardiovascular
mortality. These findings may help to identify populations for further controlled
trials and may allow a more individualized sHPT treatment using cinacalcet in
specific patient subgroups.
PMID- 28499710
TI - Impact of prealbumin on mortality and hospital readmission in patients with acute
heart failure.
AB - BACKGROUND: Prealbumin is a maker of nutritional status and inflammation of
potential prognostic value in acute heart failure (HF). The aim of this study is
to evaluate if low prealbumin levels on admission predict mortality and
readmissions in patients with acute HF. METHOD: We conducted a prospective
observational cohort study including 442 patients hospitalized for acute HF.
Patients were classified in two groups according to prealbumin levels: "normal"
prealbumin (>15mg) and "low" prealbumin (<=15mg/dL). End-points were mortality
and readmissions (all-cause and HF-related) and the combined end-point of
mortality/readmission at 180days. RESULTS: Out of 442 patients, 159 (36%) had low
and 283 (64%) had normal prealbumin levels Mean age was 79.6 (73.9-84.2, p=0,405)
years and 183 (41%, p=0,482) were males. After a median 180days of follow-up, 108
(24%, p=0,021) patients died and 170 (38%, p=0,067) were readmitted. Mortality
was higher in the low prealbumin group. The combined end-point was more frequent
in the low prealbumin group (57% vs. 50%, p=0.199). In the multivariate analysis
the following variables were associated with mortality or readmission: older age,
exacerbated chronic HF, higher comorbidity, low systolic blood pressure and
hemoglobin values and higher pro brain natriuretic peptide levels. CONCLUSIONS:
Low prealbumin is common (36%) in patients with acute heart failure and it is
associated with a higher short-term mortality.
PMID- 28499711
TI - Does an external chest wall measurement correlate with a CT-based measurement in
patients with chest wall deformities?
AB - BACKGROUND: Measurements in chest wall deformities are typically conducted using
a thorax caliper or a CT scan of the chest wall. This paper focuses on the
possible correlation between these two methods to validate the reliability of the
thorax caliper, minimize radiation exposure, and limit the usage of expensive
imaging techniques. METHODS: We evaluated 95 consecutive patients (77 pectus
excavatum (PE), 17 pectus carinatum (PC), 1 mixed deformity) who received
surgical correction of the anterior chest wall. The results of the external chest
wall measurements and the CT-based measurements were statistically compared.
RESULTS: A significant correlation between the two measurements was observed in
PE and PC at the highest point of the deformation. The strongest correlation was
noted in PE. We also noted a correlation between the transverse diameter of the
external measurement and the inner thoracic diameter of the CT scan but not for
the sagittal diameters in the upper parts of the sternum. CONCLUSIONS: Thorax
caliper measurements are suitable for determining the sagittal thoracic diameter
at the maximum level of the deformity and the transverse diameter with an
accuracy comparable to that of CT measurements. Since these values key, the
thorax caliper is reliable for monitoring and documenting chest wall
malformations. LEVEL OF EVIDENCE: Study of diagnostic test. Testing previously
developed diagnostic criteria in a consecutive series of patients and a
universally "gold" standard-Level I.
PMID- 28499712
TI - Quattro Flap Tracheotomy-The impact of a novel surgical technique for young
infants.
AB - BACKGROUND: Tracheotomy for pediatric patients is a surgical procedure with
greater technical difficulty and higher rates of morbidity and mortality than
that in adults. We report a new technique for pediatric tracheotomy that reduces
the issue of granulation and recannulation after accidental decannulation.
METHODS: Clinical data were retrospectively reviewed for 32 pediatric patients
aged 3weeks-32months who underwent Quattro Flap Tracheotomy (QFT) at our
hospital. The technique for the procedure is described and illustrated in detail.
We analyzed the complications of surgery and the prognosis of patients. RESULTS:
Twenty-seven out of 32 pediatric tracheotomy patients were aged <12months.
Overall, one patient with subglottic stenosis developed granulation and required
a resection. Three patients with granulation were cured using conservative
treatment. Neither pneumothorax nor accidental decannulation and failure to
reinsert the cannula occurred with QFT. No tracheotomy-related deaths occurred.
The overall rate of postoperative complications was lower in the study group
(4/32 cases, 12.5%) than in the control group (12/32 cases, 37.5%; p=0.041).
CONCLUSION: QFT is a new method for pediatric tracheotomy that should be
performed in younger infants. If performed appropriately, QFT may reduce the
incidence of complications and death in many cases that involve persistent
granulation. LEVELS OF EVIDENCE: IV.
PMID- 28499713
TI - Long-term outcomes of oesophageal atresia without or with proximal
tracheooesophageal fistula - Gross types A and B.
AB - PURPOSE: Because of an extended gap between esophageal pouches a variety of
methods are employed to treat oesophageal atresia (OA) without (type A) or with
(type B) proximal tracheooesophageal fistula. This retrospective observational
study describes their single centre long-term outcomes from 1947 to 2014.
METHODS: Of 693 patients treated for OA 68 (9.7%) had type A (n=58, 8.3%) or B
(n=10, 1.4%). Hospital records were reviewed. Main outcome measures were survival
and oral intake. RESULTS: Nine (13%) patients had early and 10 (15%) delayed
primary anastomosis, 30 (44%) underwent reconstruction including colonic
interposition (n=13), reversed gastric tube (n=11) and jejunum interposition
(n=6), whereas19 (28%) had died without a definite repair. Median follow up was
35 (interquartile range, 7.4-40) years. Thirty-one (63%) of 49 patients with
definitive repair survived long term. Survival was 22% for early and 80% for
delayed primary anastomosis, 57% for colon interposition, 82% for gastric tube
and 84% for jejunum interposition. Gastrooesophageal reflux was most common after
gastric tube (80%), dysphagia after colon interposition (50%), and 3 (60%) of 5
survivors with jejunum interposition had permanent feeding ostomy because of
neurological disorder. Endoscopic follow-up disclosed no oesophageal cancer or
dysplasia. Repair in the most recent patients from 1985 to 2014 (n=14) included
delayed primary anastomosis (n=7), jejunum interposition (n=6) and gastric tube
(n=1) with 93% long-term survival. CONCLUSION: Morbidity among long-term
survivors of type A or B OA is high. With modern management survival is, however,
excellent and patients without neurological disorder achieve full oral intake
either after primary anastomosis or reconstruction. LEVELS OF EVIDENCE: IV.
PMID- 28499714
TI - Seizures in Infants Born Preterm: Defining the Scale of the Problem.
PMID- 28499716
TI - Risk-Based Questionnaires Fail to Detect Adolescent Iron Deficiency and Anemia.
AB - OBJECTIVE: To evaluate the predictive ability of screening questionnaires to
identify adolescent women at high-risk for iron deficiency or iron deficiency
anemia who warrant objective laboratory testing. STUDY DESIGN: Cross-sectional
study of 96 female individuals 12-21 years old seen at an academic medical
center. Participants completed an iron deficiency risk assessment questionnaire
including the 4 Bright Futures Adolescent Previsit Questionnaire anemia
questions, along with depression, attention, food insecurity, and daytime
sleepiness screens. Multiple linear regression controlling for age, race, and
hormonal contraception use compared the predictive ability of 2 models for
adolescent iron deficiency (defined as ferritin <12 mcg/L) and anemia (hemoglobin
<12 g/dL). Model 1, the Bright Futures questions, was compared with model 2,
which included the 4 aforementioned screens and body mass index percentile.
RESULTS: Among participants, 18% (17/96) had iron deficiency and 5% (5/96) had
iron deficiency anemia. Model 1 (Bright Futures) poorly predicted ferritin and
hemoglobin values (R2 = 0.03 and 0.08, respectively). Model 2 demonstrated
similarly poor predictive ability (R2 = 0.05 and 0.06, respectively). Mean
differences for depressive symptoms (0.3, 95% CI -0.2, 0.8), attention difficulty
(-0.1, 95% CI -0.5, 0.4), food insecurity (0.04, 95% CI -0.5, 0.6), daytime
sleepiness (0.1, 95% CI -0.1, 0.3), and body mass index percentile (-0.04, 95% CI
-0.3, 0.2) were not significantly associated with ferritin in model 2. Mean
differences for hemoglobin were also nonsignificant. CONCLUSIONS: Risk-based
surveys poorly predict objective measures of iron status using ferritin and
hemoglobin. Next steps are to establish the optimal timing for objective
assessment of adolescent iron deficiency and anemia.
PMID- 28499717
TI - A call to action for outpatient antibiotic stewardship.
AB - OBJECTIVES: To address the public health threat of antibiotic resistance, there
has been an enhanced call for antibiotic stewardship programs throughout the
health care continuum. SUMMARY: While antibiotic stewardship programs have been
well described in the inpatient setting, data on effectiveness and guidance on
implementing outpatient programs is scarce. Establishing stewardship practices in
the outpatient setting is necessary because more than 60% of human antibiotic use
occurs in this setting. CONCLUSION: In this article, we highlight the importance
and need for stewardship in the outpatient setting, discuss strategies for the
development of stewardship teams, and discuss potential metrics that can be used
to assess effectiveness of antibiotic stewardship interventions.
PMID- 28499715
TI - Infant Nutritional Status and Markers of Environmental Enteric Dysfunction are
Associated with Midchildhood Anthropometry and Blood Pressure in Tanzania.
AB - OBJECTIVE: To assess whether growth and biomarkers of environmental enteric
dysfunction in infancy are related to health outcomes in midchildhood in
Tanzania. STUDY DESIGN: Children who participated in 2 randomized trials of
micronutrient supplements in infancy were followed up in midchildhood (4.6-9.8
years of age). Anthropometry was measured at age 6 and 52 weeks in both trials,
and blood samples were available from children at 6 weeks and 6 months from 1
trial. Linear regression was used for height-for-age z-score, body mass index-for
age z-score, and weight for age z-score, and blood pressure analyses; log
binomial models were used to estimate risk of overweight, obesity, and stunting
in midchildhood. RESULTS: One hundred thirteen children were followed-up. Length
for-age z-score at 6 weeks and delta length-for-age z-score from 6 to 52 weeks
were associated independently and positively with height-for-age z-score and
inversely associated with stunting in midchildhood. Delta weight-for-length and
weight-for-age z-score were also positively associated with midchildhood height
for-age z-score. The 6-week and delta weight-for-length z-scores were associated
independently and positively with midchildhood body mass index-for-age z-score
and overweight, as was the 6-week and delta weight-for-age z-score. Delta length
for-age z-score was also associated with an increased risk of overweight in
midchildhood. Body mass index-for-age z-score in midchildhood was associated
positively with systolic blood pressure. Serum anti-flagellin IgA concentration
at 6 weeks was also associated with increased blood pressure in midchildhood.
CONCLUSIONS: Anthropometry at 6 weeks and growth in infancy independently predict
size in midchildhood, while anti-flagellin IgA, a biomarker of environmental
enteric dysfunction, in early infancy is associated with increased blood pressure
in midchildhood. Interventions in early life should focus on optimizing linear
growth while minimizing excess weight gain and environmental enteric dysfunction.
TRIAL REGISTRATION: ClinicalTrials.gov: NCT00197730 and NCT00421668.
PMID- 28499718
TI - Family amyloid polyneuropathy, sympathetic denervation and liver transplantation.
PMID- 28499719
TI - Diabetes, hypoxia and cardiovascular disease: From molecular mechanism to
treatment.
PMID- 28499720
TI - T follicular helper and TH2 cells in allergic responses.
AB - IL-4 is a cytokine commonly secreted by TH2 and follicular helper T (TFH) cells
after antigenic sensitization. TH2 cells have been thought to be the major
contributor of B cell help as a source of IL-4 responsible for class switch
recombination to Immunoglobulin G1 (IgG1) and Immunoglobulin E (IgE).
Importantly, there are some differences in transcriptional regulation between
these two T cell subsets. The IL-4 production by TH2 and TFH cells is
distinctively regulated by two pathways, GATA-3-mediated Il4-HS2 enhancer and
Notch mediated Il4-CNS-2 enhancer. IgE and IgG1 antibody responses are mainly
controlled by IL-4-secreting TFH cells, but not by TH2 cells. In this review, we
discuss the role of TH2 and TFH cells in IgE production and allergic responses.
PMID- 28499721
TI - Efficacy of South African Babesia bovis vaccine against field isolates.
AB - A high-passage Babesia bovis vaccine containing only one genotype population was,
although protective, inferior compared to the immunity afforded by a lower
passage of the same strain containing two populations. The 24 times serially
passaged South African B. bovis S vaccine strain contain only a single parasite
population (Bv80 allele A 558bp). Forty-four field isolates sampled were all
found different with regard to the number and composition of the parasite
populations present in each isolate. The extensive genotypic diversity in South
Africa and the limited genotypic diversity observed in the S24 vaccine, raised
the question on its ability to protect against such diverse populations. The 6
isolates selected for challenge in the current study originated from
geographically distinct populations that also possessed thirteen unique genotypes
based on the Bv80 gene and included strains that resulted in clinical disease.
The strain coverage was therefore much greater than in previous studies on the
protective ability of the S24 vaccine. Challenge of vaccinated cattle indicated
that the vaccine gave adequate protection against 5/6 isolates. Protection
against the remaining isolate proved inadequate. However, field observations in
the region where this isolate originated from, showed only minor mortalities in
vaccinated animals compared to losses experienced in unvaccinated herds. This
study demonstrated the ability of the South African B. bovis S24 vaccine to
protect cattle against challenge from local field isolates containing single or
multiple parasite populations.
PMID- 28499722
TI - Babesia genotypes in Haemaphysalis concinna collected from birds in Hungary
reflect phylogeographic connections with Siberia and the Far East.
AB - Haemaphysalis concinna is the second most common tick species attaching to birds
in Hungary. Recently, Babesia genotypes, found in Siberia and the Far East, have
been detected in this tick species collected from the vegetation in Hungary and
Slovakia. The aim of this study was to molecularly investigate if these
piroplasms also occur in H. concinna carried by migratory birds, which might
explain their occurrence in the western Palaearctic. During a 2-year period, 321
H. concinna larvae and nymphs were collected from 121 passerine birds (of 19
species) in Hungary. These were molecularly investigated for the presence of
piroplasm DNA with PCR and sequencing. The prevalence of PCR positive ticks was
15.9% (51 out of 321). Piroplasm PCR positivity of H. concinna ticks was
significantly more frequent during the summer and autumn compared to spring,
suggesting that migratory birds arriving in Hungary from the north or north east
are the most important in the dispersal of H. concinna-associated piroplasms.
Three genotypes, i.e. Babesia sp. "Irk-Hc133", "Irk-Hc130" (originally found in
Irkutsk, Siberia) and "Kh-Hc222" (originally found in Khabarovsk, Far East) were
detected. Phylogenetically all these belonged to the group formed by Babesia spp.
of ruminants. Four bird species, which had 14-60% prevalence of PCR positive
ticks, are known to be associated with northeast to southwest autumn migration.
In conclusion, the presence of Central and East Asian Babesia genotypes in
Central Europe are most likely related to bird species with known eastern
migratory habit and/or phylogenetically substantiated connections between their
eastern and western Eurasian populations.
PMID- 28499723
TI - A dual-site gateway cloning system for simultaneous cloning of two genes for
plant transformation.
AB - Analyses of the subcellular localization of proteins and protein-protein
interaction networks are essential to uncover the molecular basis of diverse
biological processes in plants. To this end, we have created a Gateway cloning
compatible vector system, named dual-site (DS) Gateway cloning system to allow
simple cloning of two expression cassettes in a binary vector and to express them
simultaneously in plant cells. In the DS Gateway cloning system, (i) a moderate
constitutive nopaline synthase promoter (Pnos), which is much suitable for
localization analysis, is used to guide each expression cassette, (ii) four
series of vectors with different plant resistance markers are established, (iii)
N-terminal fusion with 6 fluorescent proteins and 7 epitope tags is available,
(iv) both N- and C-terminal fusions with split enhanced yellow fluorescent
protein (EYFP) are possible for efficient detection of protein-protein
interactions using a bimolecular fluorescence complementation (BiFC) assay. The
usefulness of the DS Gateway cloning system has been demonstrated by the analysis
of the expression and the subcellular localization patterns of two Golgi proteins
in stable expression system using A. thaliana, and by the analyses of
interactions between subunits of coat protein complex II (COPII) both in
transient and stable expression systems using Japanese leek and A. thaliana,
respectively. The DS Gateway cloning system provides a multipurpose, efficient
expression tool in gene function analyses and especially suitable for
investigating interactions and subcellular localization of two proteins in living
plant cells.
PMID- 28499725
TI - Antibiotic prescribing and resistance: knowledge among Latin American medical
students during Antibiotic Awareness Week 2016.
PMID- 28499724
TI - Cardio-oncology in the older adult.
AB - Heart disease and cancer are the leading causes of death in older adults. Many
first-line cancer treatments have the potential for cardiotoxicity. Age-related
risk factors, pre-existing cardiac disease, and a high prevalence of
comorbidities are reasons for increased cardiotoxicity in older adults. Concerns
regarding cardiotoxicity may lead to frailty bias and undertreatment, resulting
in suboptimal outcomes. There is an urgent need for geriatric-specific evidence
and guidelines to help tailor care for this vulnerable group. A multi
disciplinary approach based on close collaboration between oncologists,
cardiologists, and geriatricians, among other specialist clinicians is essential.
PMID- 28499726
TI - Inhibitory effect of donepezil on bradykinin-induced increase in the
intracellular calcium concentration in cultured cortical astrocytes.
AB - Donepezil is a potent and selective acetylcholinesterase inhibitor developed for
the treatment of Alzheimer's disease. In the present study, we investigated the
responses of astrocytes to bradykinin, an inflammatory mediator, and the effect
of donepezil on these responses using cultured cortical astrocytes. Bradykinin
induced a transient increase of intracellular calcium concentration ([Ca2+]i) in
cultured astrocytes. Bradykinin-induced [Ca2+]i increase was inhibited by the
exposure to thapsigargin, which depletes Ca2+ stores on endoplasmic reticulum,
but not by the exclusion of extracellular Ca2+. Twenty four hours pretreatment of
donepezil reduced the bradykinin-induced [Ca2+]i increase. This reduction was
inhibited not only by mecamylamine, a nAChR antagonist, but also by PI3K and Akt
inhibitors. In addition, donepezil inhibited bradykinin-induced increase of the
intracellular reactive oxygen species level in astrocytes. These results suggest
that donepezil inhibits the inflammatory response induced by bradykinin via nAChR
and PI3K-Akt pathway in astrocytes.
PMID- 28499727
TI - The Rush from Judgment.
PMID- 28499729
TI - Doubts about dementia diagnoses.
PMID- 28499728
TI - Push-Alert Notification of Troponin Results to Physician Smartphones Reduces the
Time to Discharge Emergency Department Patients: A Randomized Controlled Trial.
AB - STUDY OBJECTIVE: For emergency department (ED) patients with chest pain,
discharge decisions often hinge on troponin results. Push-alert notifications
deliver results immediately to physician smartphones. Our objective is to
determine whether troponin push alerts improve the time to discharge decisions
for ED patients with chest pain. METHODS: In an academic ED, we assessed the
effect of a quality improvement initiative using troponin push alerts to
physician smartphones, with a cluster-randomized evaluation. Participating
physicians were randomized to receive troponin push alerts (intervention) or not
receive them (control). We retrospectively identified patients treated by
participating physicians during the study period who were discharged from the ED
with chest pain. The primary outcome was the time from final troponin result to
discharge decision. Secondary outcomes included length of stay. A linear mixed
model was used to adjust for physician clustering. RESULTS: During the study,
1,554 patients were discharged from the ED with chest pain. There were 551
patients in the control group and 554 in the intervention group who met inclusion
criteria. The overall median interval from final troponin result to discharge
decision was 79.7 minutes (interquartile range [IQR] 33.6 to 167.8 minutes); it
was 94.3 minutes (IQR 36.2 to 177.8 minutes) in the control group and 68.5
minutes (IQR 30.5 to 157.2 minutes) in the intervention group. This 25.8-minute
difference in medians (95% confidence interval 24.6 to 28.0 minutes) was
statistically significant. Total ED length of stay was 345 minutes (IQR 261 to
419 minutes) in the control group and 328 minutes (IQR 250 to 408 minutes) in the
intervention group. CONCLUSION: Physicians who received troponin push alerts
discharged their patients with chest pain 26 minutes faster than those without
troponin notifications. Total ED length of stay did not significantly improve for
these patients.
PMID- 28499730
TI - Effects of Withdrawing alpha1-Blocker from Combination Therapy with alpha1
Blocker and 5alpha-Reductase Inhibitor in Patients with Lower Urinary Tract
Symptoms Suggestive of Benign Prostatic Hyperplasia: A Prospective and
Comparative Trial Using Urodynamics.
AB - PURPOSE: We compared the effects on lower urinary tract symptoms and bladder
outlet obstruction of combination therapy with alpha1-blocker and 5alpha
reductase inhibitor or a switch to 5alpha-reductase inhibitor monotherapy. We
determined the factors influencing changes in lower urinary tract symptoms after
alpha1-blocker withdrawal. MATERIALS AND METHODS: A total of 140 outpatients with
lower urinary tract symptoms suggestive of benign prostatic hyperplasia received
combination therapy with silodosin 8 mg per day and dutasteride 0.5 mg per day
for 12 months. Of the patients 132 were randomized to continue combination
therapy or switched to dutasteride monotherapy through silodosin withdrawal as
the monotherapy group. Parameter changes from before randomization to 12 months
after randomization were assessed based on subjective symptoms and urodynamic
findings of voiding and storage function. RESULTS: Efficacy analysis included 57
patients on combination therapy and 60 on monotherapy. The change in I-PSS
(International Prostate Symptom Score) after randomization was -0.7 and -0.6 in
the combination therapy and monotherapy groups, respectively. The bladder outlet
obstruction index changed from 46.1 to 41.8 in the combination therapy group and
from 42.9 to 39.9 in the monotherapy group. No significant differences in
subjective symptoms and bladder outlet obstruction were observed between the 2
groups. However, storage function decreased in the monotherapy group and lower
urinary tract symptoms deteriorated significantly after the switch to dutasteride
monotherapy in patients with a higher body mass index. CONCLUSIONS: We found that
alpha1-blocker withdrawal from combination therapy was reasonable and tolerable
with regard to the effect on lower urinary tract symptoms and bladder outlet
obstruction. However, withdrawal must be performed carefully in patients with a
high body mass index.
PMID- 28499731
TI - Discovery of N-substituted-endo-3-(8-aza-bicyclo[3.2.1]oct-3-yl)-phenol and
phenyl carboxamide series of MU-opioid receptor antagonists.
AB - Gastrointestinal dysfunction as a consequence of the use of opioid analgesics is
of significant clinical concern. First generation drugs to treat these opioid
induced side-effects were limited by their negative impact on opioid receptor
agonist-induced analgesia. Second generation therapies target a localized,
peripherally-restricted, non-CNS penetrant drug distribution of opioid receptor
antagonists. Herein we describe the discovery of the N-substituted-endo-3-(8-aza
bicyclo[3.2.1]oct-3-yl)-phenol and -phenyl carboxamide series of MU-opioid
receptor antagonists. This report highlights the discovery of the key MU-opioid
receptor antagonist pharmacophore and the optimization of in vitro metabolic
stability through the application of a phenol bioisostere. The compounds 27a and
31a with the most attractive in vitro profile, formed the basis for the
application of Theravance Biopharma's multivalent approach to drug discovery to
afford the clinical compound axelopran (TD-1211), targeted for the treatment of
opioid-induced constipation.
PMID- 28499732
TI - Activity of resveratrol triesters against primary acute lymphoblastic leukemia
cells.
AB - Resveratrol is a common polyphenol of plant origin known for its cancer
prevention and other properties. Its wider application is limited due to poor
water solubility, low stability, and weak bioavailability. To overcome these
limitations, a series of 13 novel resveratrol triesters were synthesized
previously. In this paper, we describe the synthesis of 3 additional derivatives
and the activity of all 16 against primary acute lymphoblastic leukemia cells. Of
these, 3 compounds were more potent than resveratrol (IC50=10.5uM) namely:
resveratryl triacetate (IC50=3.4uM), resveratryl triisobutyrate (IC50=5.1uM), and
resveratryl triisovalerate (IC50=4.9uM); all other derivatives had IC50 values of
>10uM. Further studies indicated that the active compounds caused G1 phase
arrest, increased expression of p53, and induced characteristics of apoptotic
cell death. Moreover, the compounds were only effective in cycling cells, with
cells arrested in G1 phase being refractory.
PMID- 28499733
TI - Alkaloids from aerial parts of Houttuynia cordata and their anti-inflammatory
activity.
AB - New alkaloids, houttuynamide B and C (1, 2) and houttuycorine (14), were isolated
from the aerial parts of Houttuynia cordata Thunb. in addition to eighteen known
alkaloids. Their structures were elucidated through extensive spectroscopic
analysis. All the isolates were tested for their inhibitory activity against NO
production in RAW 264.7 cells stimulated by LPS. Of the tested compounds,
compound 15 showed the most potent anti-inflammatory activity with an IC50 value
of 8.7MUM.
PMID- 28499734
TI - Preoperative controlling nutritional status (CONUT) score as a novel predictive
biomarker of survival in patients with localized urothelial carcinoma of the
upper urinary tract treated with radical nephroureterectomy.
AB - OBJECTIVE: The purpose of this study was to investigate the correlation between
the controlling nutritional status (CONUT) score and survival of patients with
localized urothelial carcinoma of the upper urinary tract treated with radical
nephroureterectomy (RNU). METHODS AND MATERIALS: We retrospectively enrolled 107
patients. CONUT score was calculated based on the serum albumin concentration,
lymphocyte count, and total cholesterol concentration. Patients were classified
into 2 groups based on CONUT score. Relapse-free survival (RFS), cancer-specific
survival (CSS), and overall survival (OS) after RNU were compared between the 2
groups, and predictors of survival were analyzed using Cox proportional hazards
regression models. RESULTS: For CONUT score, the area under the curve was 0.588
and the optimal cutoff value was 3. Twenty-four patients (22.4%) had high CONUT
scores. The patients with high CONUT scores had significantly shorter 5-year RFS,
CSS, and OS than did those with low CONUT scores (RFS: 50.1% vs. 66.0%; CSS:
28.1% vs. 71.7%; OS: 26.4% vs. 66.8%; all P<0.05). Results of the multivariable
analysis, after adjustment for factors such as pT stage, pN stage, tumor grade,
presence of lymphovascular invasion, and C-reactive protein level, revealed that
CONUT score was an independent predictor of CSS (hazard ratio [HR] = 5.44, P =
0.0016) and OS (HR = 2.90, P = 0.0214) and showed marginal significance for
predicting RFS (HR = 2.26, P = 0.0581). CONCLUSIONS: Preoperative CONUT score
helps predict survival in patients with localized urothelial carcinoma of the
upper urinary tract treated with RNU.
PMID- 28499735
TI - Turkish Standardized Reading Passage for the Evaluation of Hard Glottal Attack
Occurrence Frequency.
AB - OBJECTIVE: This study aimed to develop a Turkish reading passage that can be used
in evaluating the frequency of hard glottal attack (HGA) and to assess its
reliability. STUDY DESIGN: This is a prospective case-control study. METHODS: The
Towne-Heuer reading passage is a valuable tool that can be used for the auditory
perceptual assessment of voice. The characteristics of the first four paragraphs
of the reading passage were analyzed by a linguist. Then, a Turkish reading
passage with similar characteristics was developed. The control group (n = 21)
consisted of individuals with no voice disorder. The study group consisted of two
subgroups that were diagnosed as having vocal fold nodules (n = 11) and muscle
tension dysphonia (n = 10). A total of three listeners were evaluated for the
frequency of HGAs. One of the listeners was a master's student, whereas the other
two listeners were speech-language pathologists. Consistency between the
listeners was evaluated by using the percent agreement and the kappa statistics.
Intrarater reliability was assessed by the Wilcoxon sign test. The t test was
used to evaluate potential differences between the groups. The results were
considered as significant if the P value was <0.05. RESULTS: The average attack
number in the study group was found to be significantly higher than the controls
(P < 0.05). No significant difference could be discerned between the muscle
tension dysphonia and vocal nodule subgroups (P > 0.05). CONCLUSIONS: Findings
confirmed that HGAs are clearly related to the vocal hyperfunction; however, the
mechanism of action needs more research. In addition, the relationship between
syllable stress and HGA should be further researched to clarify the cause of the
attack number differences between English and Turkish languages.
PMID- 28499736
TI - [Children's medically complex diseases unit. A model required in all our
hospitals].
AB - INTRODUCTION: The increase in survival of children with severe diseases has led
to the rise of children with chronic diseases, sometimes with lifelong
disabilities. In 2008, a unit for the specific care of medically complex children
(MCC) was created in Hospital La Paz. OBJECTIVES: To describe the work and care
activities of this Unit. Patients and methods An analysis was performed on all
discharge reports of the Unit between January 2014 and July 2016. RESULTS: The
MCC Unit has 6 beds and daily outpatient clinic. A total of 1,027 patients have
been treated since the creation of the unit, with 243 from 2014. The median age
was 24.2 months (IQ: 10.21-84.25). The large majority (92.59%) have multiple
diseases, the most frequent chronic conditions observed were neurological
(76.95%), gastrointestinal (63.78%), and respiratory diseases (61.72%). More than
two-thirds (69.54%) of MCC are dependent on technology, 53.49% on respiratory
support, and 35.80% on nutritional support. Hospital admission rates have
increased annually. There have been 403 admissions since 2014, of which 8.93%
were re-admissions within 30 days of hospital discharge. The median stay during
2014-2016 was 6 days (IQ: 3-14). The occupancy rate has been above 100% for this
period. Currently, 210 patients remain on follow-up (86.42%), and 11 children
(4.53%) were discharged to their referral hospitals. The mortality rate is 9.05%
(22 deaths). The main condition of these 22 patients was neurological (9
patients). Infectious diseases were the leading cause of death. CONCLUSION: MCC
should be treated in specialized units in tertiary or high-level hospitals.
PMID- 28499737
TI - Endovascular Repair as a Bridge to Open Repair of a Ruptured Descending Thoracic
Aspergillus Aortitis.
AB - Invasive aspergillosis rarely involves the thoracic aorta and is associated with
a poor prognosis. A 56-year-old heart transplant recipient presented with
invasive aspergillosis, primary Aspergillus aortitis, and a ruptured thoracic
aorta pseudoaneurysm. Open surgical repair was not possible because of severe
sepsis. Therefore, a sequential surgical strategy was planned, including
emergency thoracic endovascular aortic repair, followed by antifungal treatment
and definitive open repair with explantation of the endograft and placement of a
cryopreserved arterial allograft under extracorporeal membrane oxygenator
support. The infection did not reoccur during follow-up, and the patient remained
alive and well 13 months after the operation.
PMID- 28499738
TI - Cognitive effects of subdiaphragmatic vagal deafferentation in rats.
AB - Vagal afferents are a crucial neuronal component of the gut-brain axis and
mediate the information flow from the viscera to the central nervous system.
Based on the findings provided by experiments involving vagus nerve stimulation,
it has been suggested that vagal afferent signaling may influence various
cognitive functions such as recognition memory and cognitive flexibility. Here,
we examined this hypothesis using a rat model of subdiaphragmatic vagal
deafferentation (SDA), the most complete and selective abdominal vagal
deafferentation method existing to date. We found that SDA did not affect working
memory in a nonspatial alternation task, nor did it influence short-,
intermediate-, and long-term object recognition memory. SDA did also not affect
the acquisition of positively reinforced left-right discrimination learning, but
it facilitated the subsequent reversal left-right discrimination learning. The
SDA-induced effects on reversal learning emerged in the absence of concomitant
changes in motivation towards the positive reinforcer, indicating selective
effects on cognitive flexibility. Taken together, these findings suggest that the
relative contribution of vagal afferent signaling to cognitive functions is
limited. At the same time, our study demonstrates that cognitive flexibility, at
least in the domains of positively reinforced learning, is subjected to visceral
modulation through abdominal vagal afferents.
PMID- 28499739
TI - Diatom communities on commercial biocidal fouling control coatings after one year
of immersion in the marine environment.
AB - Little is known about the effect of commercial biocidal fouling control coatings
on fouling diatom communities and their growth forms after long periods of
exposure in the marine tropical environment. The current study investigated the
abundance and composition of fouling diatom communities developed on 11
commercially available biocidal antifouling coatings, covering the three main
technology types in recent historic use (Self-Polishing Copolymers, Self
Polishing Hybrid and Controlled Depletion Polymers) after one year of static
immersion at two locations in Muscat, Oman (Marina Shangri La and Marina Bandar
Rowdha). Light microscopy demonstrated that the total abundance of diatoms and
the relative abundance of growth forms were significantly affected by the choice
of biocidal antifouling coating and experimental location. Using scanning
electron microscopy, a total of 21 diatom genera were identified which were
grouped into adnate, motile, plocon and erect growth forms. The adnate growth
forms, mainly the genera Amphora, Cocconeis and Mastogloia, dominated the other
growth forms in terms of their relative abundance. Current results revealed the
importance of exposure location and choice of biocidal antifouling coating on the
relative abundance of diatom growth forms.
PMID- 28499740
TI - Metastability in Senescence.
AB - The brain during healthy aging exhibits gradual deterioration of structure but
maintains a high level of cognitive ability. These structural changes are often
accompanied by reorganization of functional brain networks. Existing
neurocognitive theories of aging have argued that such changes are either
beneficial or detrimental. Despite numerous empirical investigations, the field
lacks a coherent account of the dynamic processes that occur over our lifespan.
Taking advantage of the recent developments in whole-brain computational modeling
approaches, we hypothesize that the continuous process of aging can be explained
by the concepts of metastability - a theoretical framework that gives a
systematic account of the variability of the brain. This hypothesis can bridge
the gap between existing theories and the empirical findings on age-related
changes.
PMID- 28499742
TI - Understanding constraints on sport performance from the complexity sciences
paradigm: An ecological dynamics framework.
AB - Glazier's suggestion for the constraints-led approach as a GUT for sport
performance is a worthy proposal. What is missing from these preliminary insights
is a principled basis, in the form of pillars, for understanding the cornerstones
of the sports medicine profession, and this lack of an overarching theoretical
framework is also somewhat of a limitation in Glazier's initial ideas, as we
argue later. Here we suggest that his preliminary proposal would benefit from
considering a more comprehensive ontological positioning within the complexity
sciences paradigm to benefit from conceptualising athletes and sports teams as
complex adaptive systems. We argue that ecological dynamics provides a more
encompassing rationale than the constraint-led approach because it is a multi
dimensional theoretical framework shaped by many relevant disciplines.
PMID- 28499741
TI - The Origins of Social Categorization.
AB - Forming conceptually-rich social categories helps people to navigate the complex
social world by allowing them to reason about the likely thoughts, beliefs,
actions, and interactions of others, as guided by group membership. Nevertheless,
social categorization often has nefarious consequences. We suggest that the
foundation of the human ability to form useful social categories is in place in
infancy: social categories guide the inferences infants make about the shared
characteristics and social relationships of other people. We also suggest that
the ability to form abstract social categories may be separable from the eventual
negative downstream consequences of social categorization, including prejudice,
discrimination, and stereotyping. Although a tendency to form inductively-rich
social categories appears early in ontogeny, prejudice based on each particular
category dimension may not be inevitable.
PMID- 28499743
TI - Resolution of the uncertainty in the kinetic mechanism for the trans-3
Chloroacrylic acid dehalogenase-catalyzed reaction.
AB - trans- and cis-3-Chloroacrylic acid dehalogenase (CaaD and cis-CaaD,
respectively) catalyze the hydrolytic dehalogenation of their respective isomers
and represent key steps in the bacterial conversion of 1,3-dichloropropene to
acetaldehyde. In prior work, a kinetic mechanism for the CaaD-catalyzed reaction
could not be unequivocally determined because (1) the order of product release
could not be determined and (2) the fluorescence factor for the enzyme species,
E*PQ (where P = bromide and Q = malonate semialdehyde, the two products of the
reaction) could not be assigned. The ambiguities in the model have now been
resolved by stopped-flow experiments following the reaction using an active site
fluorescent probe, alphaY60W-CaaD and 3-bromopropiolate, previously shown to be a
mechanism-based inhibitor of CaaD, coupled with the rate of bromide release in
the course of CaaD inactivation. A global fit of the combined datasets provides a
complete minimal model for the reaction of alphaY60W-CaaD and 3-bromoacrylate. In
addition, the global fit produces kinetic constants for CaaD inactivation by 3
bromopropiolate and implicates the acyl bromide as the inactivating species.
Finally, a comparison of the model with that for cis-CaaD shows that for both
enzymes turnover is limited by product release and not chemistry.
PMID- 28499744
TI - Does prednisone use or disease activity in pregnant women with rheumatoid
arthritis influence the body composition of their offspring?
AB - Glucocorticoids are given during pregnancy when rheumatoid arthritis (RA) is too
active. It could lead to increased risk of cardiovascular diseases (CVD) and type
2 diabetes mellitus (T2DM) in the offspring. Elevated RA disease activity during
pregnancy is associated with low birth weight and rapid post-natal growth. Both
can negatively influence the body composition later in life. This study shows
that prednisone use or RA disease activity in pregnant women with RA had no
influence on the body composition of prepubertal offspring. Furthermore, no
components of the metabolic syndrome (MetS) were present in the children, which
minimalize the change on CVD or T2DM later in life. This reassuring conclusion
might lead to a different therapeutic view when glucocorticoid treatment during
pregnancy is inevitable.
PMID- 28499745
TI - Distress in Caregivers Accompanying Patients to an Emergency Department: A
Scoping Review.
AB - BACKGROUND: Despite substantial research interest in caregiver distress in the
emergency department (ED), no recent review of the literature exists. OBJECTIVE:
Our aims were to map primary research on caregiver distress in the ED, synthesize
key concepts underpinning the literature, identify gaps, and provide guidance for
future work. METHODS: We used a five-stage scoping review with tandem screening
and data extraction. RESULTS: Of 2121 records, 29 studies were included. The
majority were small, conducted in North America or Europe, and published after
2000. Numerous methodologies and definitions of distress were represented. The
majority involved children, with just five studies restricted to adults. Many
involved higher-acuity scenarios, such as resuscitations or invasive procedures.
The most common research topic was anxiety of parents of children undergoing
procedures. Effects of witnessed resuscitation were also addressed. Parental
presence may reduce anxiety during venipuncture, while only waiting room music
reduced anxiety in parents of children not undergoing a procedure. No study
explored interventions to reduce distress in caregivers of adults. While
heterogeneity precluded evidence-based recommendations, clinically relevant
observations emerged, including that anxiety can be worsened if a caregiver
believes their patient has been forgotten; that parents are sensitive about being
perceived as neglectful; and that sympathy and confidence ease distress, as does
sensitivity toward end-of-life issues. Several studies suggested that negative
staff behaviors affect caregiver anxiety. CONCLUSIONS: Future studies should use
validated measures of distress; include larger samples; and capture adult,
geriatric, and rural populations. A focused systematic review might yield
evidence-based guidance for clinicians.
PMID- 28499746
TI - Comparing Access to Laser Capsulotomy Performed by Optometrists and
Ophthalmologists in Oklahoma by Calculated Driving Distance and Time.
AB - PURPOSE: To quantify Medicare beneficiary proximity to his or her yttrium
aluminum-garnet (YAG) laser capsulotomy-providing ophthalmologist and optometrist
in Oklahoma by calculating driving distances and times. DESIGN: Cross-sectional
cohort study using 2014 Oklahoma Medicare 100% and 5% data sets and Google Maps
distance and travel time application programming interfaces. PARTICIPANTS: U.S.
fee-for-service Medicare beneficiaries and Oklahoma ophthalmologist and
optometrist laser capsulotomy providers. METHODS: The 2014 Medicare Provider
Utilization and Payment Limited 100% and 5% datasets from the Centers for
Medicare and Medicaid (CMS) were obtained to identify the office street addresses
of Oklahoma ophthalmologists and optometrists who submitted claims to Medicare
for a YAG laser capsulotomy, and the county addresses of the corresponding
Medicare beneficiaries who received the laser capsulotomy. The shortest travel
distances and travel times between the beneficiary and the laser provider were
calculated by using Google Maps distance and travel time application programming
interfaces. MAIN OUTCOME MEASURES: Beneficiary driving distances and times to his
or her YAG laser capsulotomy-providing Oklahoma ophthalmologist and optometrist.
RESULTS: In 2014, 90 (57%) of 157 Oklahoma ophthalmologists and 65 (13%) of 506
Oklahoma optometrists submitted a total of 7521 and 3751 YAG laser capsulotomy
claims to Medicare, respectively. By using the Medicare Limited 5% dataset, there
was no difference in driving distance between beneficiaries who received a laser
capsulotomy from an ophthalmologist (median, 39 miles; interquartile range [IQR],
13-113 miles) compared with an optometrist (median, 46 miles; IQR, 13-125 miles;
P = 0.93) or in driving time to an ophthalmologist (median, 47 minutes; IQR, 19
110 minutes) compared with an optometrist (median, 50 minutes; IQR, 17-117
minutes; P = 0.76). CONCLUSIONS: For Medicare beneficiaries, there was no
difference in geographic access to YAG laser capsulotomy whether performed by an
Oklahoma ophthalmologist or optometrist as determined by calculated driving
distances and times.
PMID- 28499747
TI - Preoperative Posturing of Patients with Macula-On Retinal Detachment Reduces
Progression Toward the Fovea.
AB - PURPOSE: Traditionally, preoperative posturing consisting of bed rest and
positioning is prescribed to patients with macula-on retinal detachment (RD) to
prevent RD progression and detachment of the fovea. Execution of such advice can
be cumbersome and expensive. This study aimed to investigate if preoperative
posturing affects the progression of RD. DESIGN: Prospective cohort study.
PARTICIPANTS: Ninety-eight patients with macula-on RD were included. Inclusion
criteria were volume optical coherence tomography (OCT) scans could be obtained
with sufficient quality; and the smallest distance from the fovea to the
detachment border was 1.25 mm or more. METHODS: Patients were admitted to the
ward for bed rest in anticipation of surgery and were positioned on the side
where the RD was mainly located. At baseline and before and after each
interruption for meals or toilet visits, a 37 degrees *45 degrees OCT volume
scan was performed using a wide-angle Spectralis OCT (Heidelberg Engineering,
Heidelberg, Germany). The distance between the nearest point of the RD border and
fovea was measured using a custom-built measuring tool. MAIN OUTCOME MEASURES:
The RD border displacement and the average RD border displacement velocity moving
toward (negative) or away (positive) from the fovea were determined for intervals
of posturing and interruptions. RESULTS: The median duration of intervals of
posturing was 3.0 hours (interquartile range [IQR], 1.8-14.0 hours; n = 202) and
of interruptions 0.37 hours (IQR, 0.26-0.50 hours; n = 197). The median RD border
displacement was 2 MUm (IQR, -65 to +251 MUm) during posturing and -61 MUm (IQR,
140 to 0 MUm) during interruptions, a statistically significant difference (P <
0.001, Mann-Whitney U test). The median RD border displacement velocity was +1
MUm/hour (IQR, -21 to +49 MUm/hour) during posturing and -149 MUm/hour (IQR, -406
to +1 MUm/hour) during interruptions, a statistically significant difference (P <
0.001). CONCLUSIONS: By making use of usual interruptions of preoperative
posturing we were able to show, in a prospective and ethically acceptable manner,
that RD stabilizes during posturing and progresses during interruptions in
patients with macula-on RD. Preoperative posturing is effective in reducing
progression of RD.
PMID- 28499748
TI - Rates of Local Retinal Nerve Fiber Layer Thinning before and after Disc
Hemorrhage in Glaucoma.
AB - PURPOSE: To investigate longitudinal temporal and spatial associations between
disc hemorrhage (DH) and rates of local retinal nerve fiber layer (RNFL) thinning
before and after DHs. DESIGN: Longitudinal, observational cohort study.
PARTICIPANTS: Forty eyes of 37 participants (23 with glaucoma and 17 with suspect
glaucoma at baseline) with DH episodes during follow-up from the Diagnostic
Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation
Study. METHODS: All subjects underwent optic disc photography annually and
spectral-domain optical coherence tomography (OCT) RNFL thickness measurements
every 6 months. The rates of RNFL thinning were calculated using multivariate
linear mixed-effects models before and after DH. MAIN OUTCOME MEASURES: Rates of
global and local RNFL thinning. RESULTS: Thirty-six eyes of 33 participants with
inferior or superior DHs were analyzed. The rates of RNFL thinning were
significantly faster in DH quadrants than in non-DH quadrants after DH (-2.25 and
-0.69 MUm/year; P < 0.001). In the 18 eyes with intensified treatment after DH,
the mean rate of RNFL thinning significantly slowed after treatment compared with
before treatment in the non-DH quadrants (-2.89 and -0.31 MUm/year; P < 0.001),
but not in the DH quadrants (-2.64 and -2.12 MUm/year; P = 0.19). In 18 eyes with
unchanged treatment, the rate of RNFL thinning in the DH quadrant was faster
after DH than before DH (P = 0.008). Moreover, compared with eyes without a
treatment change, intensification of glaucoma treatment after DH significantly
reduced the global, non-DH quadrants, and DH quadrant rates of RNFL thinning
after DH compared with before DH (global, P = 0.004; non-DH quadrant, P < 0.001;
DH quadrant, P = 0.005). In the multiple linear regression analysis, treatment
intensification (beta, 1.007; P = 0.005), visual field mean deviation (beta,
0.066; P = 0.049), and difference in intraocular pressure before and after DH
(beta, -0.176; P = 0.034) were associated significantly with the difference of
global RNFL slope values before and after DH. CONCLUSIONS: Although the rate of
RNFL thinning worsened in a DH quadrant after DH, glaucoma treatment
intensification may have a beneficial effect in reducing this rate of thinning.
PMID- 28499749
TI - A double blinded prospective randomized trial comparing the effect of anatomic
versus non-anatomic resection on hepatocellular carcinoma recurrence.
AB - BACKGROUND: The aim of this study was to determine the effect of anatomic
resection (AR) versus non-anatomic resection (NAR) on recurrence rates in
patients with hepatocellular carcinoma (HCC). METHODS: Eligible patients were
randomized to AR or NAR from January 2006 to July 2007 at a single center. The
primary outcome was the 2-year recurrence-free survival (RFS). Secondary outcomes
were postoperative complications, time to first recurrence, 1-, 3-, and 5-year
RFS, and overall survival (OS). RESULTS: Fifty-three (51%) and 52 (50%) patients
underwent NAR and AR, respectively. A larger proportion of patients achieved
margins >=20 mm in the AR group (52% vs. 30%; P = 0.023). Complications (blood
loss, transfusion requirement, and hospital stay) were similar between the two
groups. Median follow-up was 33 (range, 2-77) months. Incidence of local
recurrence at 2 years was 30% and 59% in the AR and NAR groups, respectively.
Median time to first local recurrence in the AR group was significantly longer
than in the NAR group (53 vs. 10 months, P = 0.010). There was no difference in
overall RFS between the two groups (P = 0.290). DISCUSSION: AR decreased the 2
year local recurrence rate and increased the time to first local recurrence
compared to NAR in patients with HCC.
PMID- 28499750
TI - Ticket to Ride: Targeting Proteins to Exosomes for Brain Delivery.
PMID- 28499751
TI - Expanding Access to Sexual and Reproductive Health Services Through Nursing
Education.
AB - Thoughtful, unbiased, evidence-based content in nursing education is crucial for
the development of confident and competent nurses who provide care in every
setting. The purpose of this article is twofold: to provide evidence to show that
comprehensive sexual and reproductive health care by nurses is informed by
educational exposure to content and to provide recommendations for change at the
individual, institutional, and structural levels to improve and expand sexual and
reproductive health services.
PMID- 28499752
TI - Principles of Supportive Psychotherapy for Perinatal Distress.
AB - Although interpersonal psychotherapy and cognitive behavioral therapy have
demonstrated efficacy in the treatment of perinatal distress, supportive
psychotherapy has not been as widely studied by researchers. However, the
principles of supportive psychotherapy are essential in the treatment of
perinatal distress. The purpose of this article is to show that supportive
psychotherapy is a plausible intervention that nurses and other maternity care
providers can use with women who experience anxiety and depression in the
perinatal period.
PMID- 28499753
TI - Emotional intelligence and stress management in Nursing professionals in a
hospital emergency department.
AB - OBJECTIVE: To determine stress levels and to identify if there is a relationship
between emotional intelligence and work stress in nurses and healthcare
assistants of the Emergency Department. METHOD: Observational, descriptive and
cross-sectional study with a quantitative approach. The population were nurses
and healthcare assistants of the Emergency Department of the University Hospital
of Ourense. The data were collected between January and May 2016. The tool used
was a validated, anonymous, and self-administered questionnaire that included the
Trait Meta-Mood Scale and Moreno's Brief Burnout Questionnaire. The study was
approved by the Clinical Research Ethics Committee of Galicia. Descriptive and
association analyses were performed using the SPSS 15.0 statistics program.
RESULTS: A total of 60 professionals participated, of whom 36 were qualified
nurses and 24 were auxiliary nurses. The response rate was 68.1%. The results
showed a deficiency in emotional care, with a score of 22.87, while emotional
clarity and reparation of emotions were situated within normal levels, with
values of 26.42 and 26.60, respectively. The burnout levels of the sample were
medium-high. The mean score in the depersonalisation dimension was 8.05, whereas
emotional fatigue obtained a mean of 6.90, with a value of 7.50 for professional
fulfilment. Significant positive correlations were found between the employment
situation and emotional clarity (r=.276; P=.033), and between the latter and
personal fulfilment (r=.277; P=.032), and organisation (r=.316; P=.014).
CONCLUSIONS: Nurses and healthcare assistants of the Emergency Department showed
medium-high average levels of burnout, with depersonalisation being the symptom
that reflects the highest values. Emotional Intelligence is related to work
stress and, specifically, the understanding of one's own emotional states
influences personal fulfilment. Professionals with more job stability show a
better capacity to feel and express their feelings.
PMID- 28499754
TI - Methotrexate-induced epidermal necrosis: A case series of 24 patients.
AB - BACKGROUND: Methotrexate-induced epidermal necrosis (MEN) is a rare but life
threatening cutaneous reaction that mimics Stevens-Johnson syndrome (SJS) and
toxic epidermal necrolysis (TEN). OBJECTIVES: To investigate the
clinicopathology, risk factors, and prognostic factors of MEN. METHODS: We
enrolled 24 patients with MEN and 150 controls and analyzed the demographics,
pathology, and plasma concentrations of methotrexate (MTX). RESULTS: Patients
with MEN showed extensive skin necrosis (mean, 33.2% total body surface area) but
no target lesions. The histopathology displayed keratinocyte dystrophy. Early
signs of MEN included painful skin erosions, oral ulcers, and
leukopenia/thrombocytopenia. Although 79.2% patients received leucovorin
treatment, there was 16.7% mortality. Risk factors for MEN included older age
(>60 years), chronic kidney disease, and high initial dosage of MTX without folic
acid supplementation. Renal insufficiency delayed MTX clearance. Severe renal
disease and leukopenia predicted poor prognosis in MEN, but none of the SCORe of
Toxic Epidermal Necrosis criteria were associated with mortality of MEN.
LIMITATIONS: The study was limited by the small sample size. CONCLUSION: MEN
exhibited distinct clinicopathologic features from SJS/TEN. Recognition of the
early signs and prognostic factors is important, because the rapid institution of
leucovorin may be helpful. To reduce the risk of MEN, physicians should avoid
prescribing MTX to high-risk patients and titrate the dosage slowly upward with
folic acid supplementation.
PMID- 28499755
TI - Biological characteristics and karyotiping of a new isolation method for human
adipose mesenchymal stem cells in vitro.
AB - OBJECTIVE: A new method was presented to prepare clinical-grade human adipose
derived stromal stem cells (ASCs) and its safety in vitro, such as biological
characteristics and genetic features alteration were investigated. METHODS: The
morphology of the ASCs which were cultured in vitro using serum-free medium was
observed. Cell cycle and CD markers profile were tested by flow cytometry, while
karyotype was analyzed by the chromosome G-banding technology. Growth factors
expression was tested by ELISA and tumor-related genes were analyzed by the real
time PCR, respectively. RESULTS: ASCs were adult stem cells with spindle shape.
The proliferation ratio of ASCs began to slow down after 10 passages, and was
significant after 15 passages. Cell cycle analysis revealed that the percentage
of G2 phase and S phase cells was stable. There was no obvious missing,
translocation or dislocation in terms of karyotype. Expression level of tumor
relevant genes and cytokines at different passages had no significant difference.
CONCLUSIONS: The clinical-grade ASCs prepared with this new method, less than ten
passages, was safe for clinical trials.
PMID- 28499757
TI - Hidradenitis Suppurativa Is Associated with Familial Mediterranean Fever-A
Population-Based Study.
PMID- 28499756
TI - Genetic Variants in WNT2B and BTRC Predict Melanoma Survival.
AB - Cutaneous melanoma (CM) is the most lethal skin cancer. The Wnt pathway has an
impact on development, invasion, and metastasis of CM, thus likely affecting CM
prognosis. Using data from a published genome-wide association study from The
University of Texas MD Anderson Cancer Center, we assessed the associations of
19,830 common single-nucleotide polymorphisms (SNPs) in 151 Wnt pathway autosomal
genes with CM-specific survival and then validated significant SNPs in another
genome-wide association study from Harvard University. In the single-locus
analysis, 1,855 SNPs were significantly associated with CM-specific survival at P
< 0.05, of which 547 SNPs were still considered noteworthy after the correction
by the false-positive report probability. In the replication, two SNPs remained
significantly associated with CM-specific survival after multiple comparison
correction. By performing functional prediction and stepwise selection, we
identified two independent SNPs (i.e., WNT2B rs1175649 G>T and BTRC rs61873997
G>A) that showed a predictive role in CM-specific survival, with an effect-allele
attributed hazards ratio (adjusted hazards ratio) of 1.99 (95% confidence
interval = 1.41-2.81, P = 8.10 * 10-5) and 0.61 (0.46-0.80, 3.12*10-4),
respectively. Collectively, these variants in the Wnt pathway genes may be
biomarkers for outcomes of patients with CM, if validated by larger studies.
PMID- 28499758
TI - Activating CYSLTR2 and PLCB4 Mutations in Primary Leptomeningeal Melanocytic
Tumors.
PMID- 28499759
TI - Trends in Operating Room Assistance for Major Urologic Surgical Procedures: An
Increasing Role for Advanced Practice Providers.
AB - OBJECTIVE: To characterize changes in surgical assistance patterns over time for
commonly performed urologic operations. MATERIALS AND METHODS: This study used
the Medicare Physician/Supplier Procedure Summary Master File to identify cases
performed by urologists from 2003 to 2014. Current Procedural Terminology
modifiers were used to identify operations assisted by second surgeons and
advanced practice providers (APPs). Rates were reported annually for 6 common
urologic operations, and average annual rates of change were determined using
least squares regression and tested using t tests (alpha = .05). RESULTS: Of the
urologic operations analyzed, 5.0% of cases (n = 33,895) were assisted by APPs
compared with 27.0% (n = 182,842) assisted by a second surgeon. The proportion of
cases assisted by an APP rose significantly for all procedures; conversely, the
proportion of cases assisted by a second surgeon declined significantly for all
procedures, except for open partial nephrectomy. The largest changes were seen in
robotic prostatectomies for which second surgeon assistance fell from 26% in 2004
to 15% in 2014, whereas APP assistance rose from <1% to 7%. CONCLUSION:
Urologists are increasingly using APPs as assistants in surgery, particularly in
robotic and laparoscopic operations. This trend will likely continue as the
shortage of urologists worsens in the coming years.
PMID- 28499760
TI - Henoch-Schonlein Purpura With Testicular Necrosis: Sonographic Findings at the
Onset, During Treatment, and at Follow-up.
AB - Henoch-Schonlein purpura (HSP) with involvement of the testes is extremely rare.
Here, we present a pediatric case of HSP involving testicular ischemic necrosis
in an 8-year-old child. Ultrasonography plays an important role not only in the
differential diagnosis at onset, but also in the assessment of treatment response
and prognosis during treatment and at follow-up. In this case report, we present
the sonographic images for the entire course of testicular involvement in HSP and
reveal histopathologically the pathogeny as testicular autoimmune vasculitis
caused by the deposition of immunoglobulin A-containing immune complexes in the
testicular vessels.
PMID- 28499761
TI - Cystadenoma of the Rete Testis in a Patient With von Hippel-Lindau Disease.
AB - von Hippel-Lindau disease is a rare, inherited multicystic disorder that is
characterized by several benign and malignant neoplasms (Odrzywolski, 2010).
Classically, the disease manifests itself in a broad spectrum, including renal
cell carcinomas, intracranial and spinal hemangioblastomas, endolymphatic sac
tumors, renal and pancreatic cysts, and pheochromocytomas. Another important, but
commonly forgotten manifestation is the cystadenoma of the rete testis.
PMID- 28499762
TI - Ureteral Wall Thickness as a Preoperative Indicator of Impacted Stones in
Patients With Ureteral Stones Undergoing Ureteroscopic Lithotripsy.
AB - OBJECTIVE: To evaluate the clinical significance of ureteral wall thickness (UWT)
to predict the presence of impacted stones in patients with ureteral stones
undergoing ureteroscopic lithotripsy (URSL). MATERIALS AND METHODS: We
retrospectively analyzed 130 procedures in patients with ureteral stones who
underwent URSL between January 2014 and September 2016. Maximum UWT at the stone
site was measured from computed tomography images. Clinical predictors of
impacted stones were assessed using univariate and multivariate logistic
regression analyses. Receiver operating characteristic curve analysis was applied
to determine the UWT cutoff value and to evaluate its accuracy in predicting
impacted stones. Moreover, we evaluated the association between UWT and
endoscopic findings, as well as surgical outcomes. RESULTS: Of the 130
procedures, 50 (38.5%) involved patients with impacted stones. The univariate
analysis showed significant differences in age, hydronephrosis, stone location,
stone burden, and UWT in patients with and without impacted stones, and the
multivariate analysis showed that age, stones in the middle ureter, and UWT (odds
ratio 5.43, P < .001) were independent predictors of impacted stones. The
receiver operating characteristic analysis showed that 3.49 mm was the optimal
cutoff value for UWT, with a predictive accuracy of 0.87. High UWTs were
associated with the presence of ureteral edema, polyps, white lesions, stone
fixation, longer operation time, and lower endoscopic stone-free rate, compared
with low UWTs (P < .05 each). CONCLUSION: High UWT is associated not only with a
higher risk of impacted stones but also with poor endoscopic findings and adverse
surgical outcomes in patients with ureteral stones undergoing URSL.
PMID- 28499763
TI - Hydronephrosis Secondary to an Ectopic Decidual Reaction in the Urinary Bladder.
AB - A 28-year-old pregnant woman at 19 weeks gestation presented with dysuria as well
as lower abdominal and left flank pain. Imaging revealed left-sided
hydronephrosis and a mass invading the posterior bladder wall. Management
included placement of a left nephrostomy tube and transurethral resection of ~25%
of the mass. Microscopy showed an ectopic decidual reaction within the muscularis
propria. The patient improved symptomatically and continued prenatal care.
Complete resolution of her ureteral obstruction was demonstrated during the
postpartum period. Ectopic decidual reactions involving the urinary bladder are
extremely rare, and ureteral obstruction secondary to this phenomenon has not yet
been reported.
PMID- 28499764
TI - [Personal health records on the Internet. A narrative review of attitudes,
expectations, utilization and effects on health outcomes].
AB - BACKGROUND: The integration of information and communication technologies (ICT)
is increasingly considered in the development of healthcare structures. This fact
is also recognised in the e-Health Act. In this context, personal health records
(PHR) have a specific meaning. The aim of this paper is to provide an overview on
utilization, barriers and possible effects on the implementation of PHR. METHODS:
This analysis is based on a literature search in Web of Science (Core Collection)
(01/2000 to 12/2014) using the following terms: "personal health record",
"personal medical record", "personal electronic health record", "interpersonal
health record", "personally controlled health record". RESULTS: In general,
patients have positive attitudes towards the electronic exchange of personal
health information (PHI) on a PHR. Even the sharing of PHI with physicians,
health professionals, family and friends appears to be an option for many
patients. Physicians also see the potential of a PHR on the internet, but they
are more critical than patients. Barriers exist towards the use of complex and
non-intuitive PHR concepts along with technical faults and the lack of
functionality. From the physicians' perspective, prejudices concerning the use of
PHR have not been confirmed and, other than previously expected, the workload has
not increased so much. However, clinical outcomes have so far been rather
moderate. Stronger effects may be achieved by embedding the PHR in a broader
healthcare concept. CONCLUSION: In the context of chronic disease, a connected
PHR (patient-controlled, cross-sectoral, and interoperable) can be a valuable
tool for organizing healthcare for patients. To take full effect, the development
of such systems should focus on patients and their families as well as on
physicians and other healthcare professionals. Whether the e-Health Act is a step
in the right direction will have to be established by future analysis.
PMID- 28499765
TI - CKD-EPI equation: A suitable Glomerular Filtration Rate estimate for drug dosing
in HIV-infected patients.
AB - OBJECTIVES: To evaluate concordance between glomerular filtration rate (GFR)
estimates (Cockcroft and Gault, modification of diet in renal diseases, chronic
kidney disease epidemiology study group equations) for drug dosing in HIV
infected patients. PATIENTS AND METHODS: We performed a monocentric study. GFR
was measured using the gold standard method (plasma clearance of iohexol) in 230
HIV-infected patients. Concordance rate was evaluated between measured GFR (mGFR)
and estimated GFR (eGFR) for different GFR categories (GFR>90 mL/min, GFR<90
mL/min, GFR>70 mL/min, and GFR<70 mL/min). MDRD and CKD-EPI were used with and
without indexation to body surface area (BSA). RESULTS: Mean age was 48+/-10
years, mean mGFR was 101+/-26 mL/min. Concordance between mGFR and eGFR estimated
with CG, CKD-EPI (indexed and not indexed to BSA), or MDRD equations (not indexed
to BSA) was similar (73%, 73%, 74%, and 73% respectively) for a breakpoint value
of 90 mL/min for GFR. At this value, the concordance rate between mGFR and MDRD
indexed to BSA was significantly lower (65%, P<0.05). Using 70 mL/min of GFR as
the breakpoint value, all equations had similar concordance rates with mGFR (with
or without indexation to BSA). CONCLUSION: CKD-EPI equation has the same
concordance with GFR and with CG when used for drug dosing.
PMID- 28499766
TI - Comparing early signs and basic symptoms as methods for predicting psychotic
relapse in clinical practice.
AB - BACKGROUND: Early signs interventions show promise but could be further
developed. A recent review suggested that 'basic symptoms' should be added to
conventional early signs to improve relapse prediction. This study builds on
preliminary evidence that basic symptoms predict relapse and aimed to: 1. examine
which phenomena participants report prior to relapse and how they describe them;
2. determine the best way of identifying pre-relapse basic symptoms; 3. assess
current practice by comparing self- and casenote-reported pre-relapse
experiences. METHODS: Participants with non-affective psychosis were recruited
from UK mental health services. In-depth interviews (n=23), verbal checklists of
basic symptoms (n=23) and casenote extracts (n=208) were analysed using directed
content analysis and non-parametric statistical tests. RESULTS: Three-quarters of
interviewees reported basic symptoms and all reported conventional early signs
and 'other' pre-relapse experiences. Interviewees provided rich descriptions of
basic symptoms. Verbal checklist interviews asking specifically about basic
symptoms identified these experiences more readily than open questions during in
depth interviews. Only 5% of casenotes recorded basic symptoms; interviewees were
16 times more likely to report basic symptoms than their casenotes did.
CONCLUSIONS: The majority of interviewees self-reported pre-relapse basic
symptoms when asked specifically about these experiences but very few casenotes
reported these symptoms. Basic symptoms may be potent predictors of relapse that
clinicians miss. A self-report measure would aid monitoring of basic symptoms in
routine clinical practice and would facilitate a prospective investigation
comparing basic symptoms and conventional early signs as predictors of relapse.
PMID- 28499767
TI - Routine patient reported outcomes as predictors of psychiatric rehospitalization.
AB - OBJECTIVE: Patient reported outcome measures (PROMs) are increasingly used to
measure psychiatric service consumers' progress and to provide feedback to
consumers and providers. We tested whether PROMs can predict and be used to
identify groups at high risk for future hospitalization. METHODS: A total of 2842
Israeli users of psychiatric rehabilitation services reported on their quality of
life (QoL) and the effect of symptoms on their daily functioning. Survey data
were linked with information on psychiatric hospitalization 6 and 12months after
survey completion. Variables associated with each of the outcomes were tested for
significance and entered into a multivariate logistic regression model.
Prediction scores were developed to identify the highest-risk groups according to
each model. RESULTS: QoL was found to be a significant predictor of future
hospitalization within 6months (odds ratio [OR]=0.71, 95% CI: 0.59-0.86), and
self-report of the impact of symptoms on functioning significantly predicted 12
month hospitalization (OR=0.83, 95% CI: 0.74-0.93), controlling for known risk
factors. Positive predictive values for the 6- and 12-month risk scores were 31.1
and 40.4, respectively, for the 10% highest risk categories. CONCLUSIONS: Reports
of psychiatric service consumers on their QoL and on the effect of symptoms on
their functioning significantly predict of future hospitalization risk, beyond
other well-known risk factors. PROMs can identify consumers at high risk for
future hospitalization and thus direct interventions for those at highest risk.
PMID- 28499768
TI - Mortality in people with psychotic disorders in Finland: A population-based 13
year follow-up study.
AB - OBJECTIVES: We conducted a population based study aiming at finding predictors of
mortality in psychotic disorders and evaluating the extent to which
sociodemographic, lifestyle and health-related factors explain the excess
mortality. METHODS: In a nationally representative sample of Finns aged 30
70years (n=5642), psychotic disorders were diagnosed using structured interviews
and medical records in 2000-2001. Information on mortality and causes of death
was obtained of those who died by the end of year 2013. Cox proportional hazards
models were used to investigate the mortality risk. RESULTS: No people with
affective psychoses (n=36) died during the follow-up, thus the analysis was
restricted to non-affective psychotic disorders (NAP) (n=106). Adjusting for age
and sex, NAP was statistically significantly associated with all-cause mortality
(hazard ratio (HR) 2.99, 95% CI 2.03-4.41) and natural-cause mortality (HR 2.81,
95% CI 1.85-4.28). After adjusting for sociodemographic factors, health status,
inflammation and smoking, the HR dropped to 2.11 (95% CI 1.10-4.05) for all-cause
and to 1.98 (95% CI 0.94-4.16) for natural-cause mortality. Within the NAP group,
antipsychotic use at baseline was associated with reduced HR for natural-cause
mortality (HR 0.25, 95% CI 0.07-0.96), and smoking with increased HR (HR 3.54,
95% CI 1.07-11.69). CONCLUSIONS: The elevated mortality risk in people with NAP
is only partly explained by socioeconomic factors, lifestyle, cardio-metabolic
comorbidities and inflammation. Smoking cessation should be prioritized in
treatment of psychotic disorders. More research is needed on the quality of
treatment of somatic diseases in people with psychotic disorders.
PMID- 28499769
TI - Structure, biochemical and kinetic properties of recombinant Pst2p from
Saccharomyces cerevisiae, a FMN-dependent NAD(P)H:quinone oxidoreductase.
AB - The genome of the yeast Saccharomyces cerevisiae encodes four flavodoxin-like
proteins, namely Lot6p, Pst2p, Rfs1p and Ycp4p. Thus far only Lot6p was
characterized in detail demonstrating that the enzyme possesses NAD(P)H:quinone
oxidoreductase activity. In the present study, we heterologously expressed PST2
in Escherichia coli and purified the produced protein to conduct a detailed
biochemical and structural characterization. Determination of the three
dimensional structure by X-ray crystallography revealed that Pst2p adopts the
flavodoxin-like fold and forms tetramers independent of cofactor binding. The
lack of electron density for FMN indicated weak binding, which was confirmed by
further biochemical analysis yielding a dissociation constant of 20+/-1MUM. The
redox potential of FMN bound to Pst2p was determined to -89+/-3mV and is thus
119mV more positive than that of free FMN indicating that reduced FMN binds ca.
five orders of magnitude tighter to Pst2p than oxidized FMN. Due to this rather
positive redox potential Pst2p is unable to reduce free FMN or azo dyes as
reported for other members of the flavodoxin-like protein family. On the other
hand, Pst2p efficiently catalyzes the NAD(P)H dependent two-electron reduction of
natural and artificial quinones. The kinetic mechanism follows a ping-pong bi-bi
reaction scheme. In vivo experiments with a PST2 knock out and overexpressing
strain demonstrated that Pst2p enables yeast cells to cope with quinone-induced
damage suggesting a role of the enzyme in managing oxidative stress.
PMID- 28499770
TI - Development of active, nanoparticle, antimicrobial technologies for muscle-based
packaging applications.
AB - Fresh and processed muscle-based foods are highly perishable food products and
packaging plays a crucial role in providing containment so that the full effect
of preservation can be achieved through the provision of shelf-life extension.
Conventional packaging materials and systems have served the industry well,
however, greater demands are being placed upon industrial packaging formats owing
to the movement of muscle-based products to increasingly distant markets, as well
as increased customer demands for longer product shelf-life and storage
capability. Consequently, conventional packaging materials and systems will have
to evolve to meet these challenges. This review presents some of the new
strategies that have been developed by employing novel nanotechnological concepts
which have demonstrated some promise in significantly extending the shelf-life of
muscle-based foods by providing commercially-applicable, antimicrobially-active,
smart packaging solutions. The primary focus of this paper is applied to subject
aspects, such as; material chemistries employed, forming methods utilised,
interactions of the packaging functionalities including nanomaterials employed
with polymer substrates and how such materials ultimately affect microbes. In
order that such materials become industrially feasible, it is important that
safe, stable and commercially-viable packaging materials are shown to be
producible and effective in order to gain public acceptance, legislative approval
and industrial adoption.
PMID- 28499771
TI - The key role of the meat industry in transformation to a low-carbon, climate
resilient, sustainable economy.
AB - Climate change, air pollution and refugees have become key global challenges
threatening sustainability of lifestyles, economies and ecosystems. Agri-food
systems are the number one driver of environmental change. Livestock production
is the world's largest land user, responsible for half of greenhouse gas
emissions from agri-food systems, and the source of repeated health crises. Poor
diets have become the number one cause of ill health. Recommendations for a
healthy diet emphasize plant-based food. Rapidly falling costs in information
technology, biotechnology, renewable energy and battery technology will disrupt
current energy and transportation systems and offer opportunities for responsible
meat production. Growing consumer interest in healthy food, combined with
innovative information systems, offer opportunities to create value through
quality control and consumer information in integrated value chains. Meat
scientists have a major role to play in the necessary transformation of global
agri-food systems towards a new model of green economic growth that is climate
resilient, sustainable and provides green jobs.
PMID- 28499772
TI - Exploring Patient Engagement: A Qualitative Analysis of Low-Income Urban
Participants in Asthma Research.
AB - BACKGROUND: Uncontrolled asthma is a common highly morbid condition with worse
outcomes in low-income and minority patients in part due to barriers accessing
and engaging with health care. We developed a patient advocate to educate about
and assist with navigating access to care and provider-patient communication.
Participants completed an End of Study Questionnaire (ESQ) that was analyzed to
assess experience and engagement with the protocol. OBJECTIVE: This study uses
qualitative analysis to evaluate participant experience with the patient advocate
and control group interventions. METHODS: The ESQ aimed to prompt an open-ended
discussion of study experience. Questions were developed from patient focus
groups about the patient advocate intervention (PAI), and were revised based on
early responses. The questionnaire was administered after 12 months of study
participation: 6 months of control or PAI, followed by 6 months of follow-up.
Answers were evaluated using qualitative coding and a grounded theory analytical
approach. RESULTS: A total of 102 low-income and minority adults with moderate or
severe asthma who had completed the study protocol at the time of publication
(approximately one-third of total participants) found PAI and control group
activities acceptable. Four themes emerged from both groups: (1) appreciation of
interpersonal and educational interaction, (2) perception of improved health care
adherence, (3) preparedness for physician appointments, (4) improved patient
provider communication. Attention from study personnel and review of asthma
related information was unanimously well received and empowered patients' active
health care participation. CONCLUSIONS: Patient engagement and empowerment were
elicited by perceived education and personal attention. This study suggests a low
resource, feasible method to improve patient engagement.
PMID- 28499773
TI - Stability of Asthma Symptom Control in a Longitudinal Study of Mild-Moderate
Asthmatics.
AB - BACKGROUND: Achieving and maintaining symptom control is a primary goal of asthma
management. Although factors associated with the likelihood of achieving symptom
control have been studied, there are unanswered questions on the stability of
symptom control, that is, the tendency of individuals to remain at a given
symptom control level over time. OBJECTIVE: The objective of this study was to
evaluate the stability of symptom control using a longitudinal cohort of mild
moderate asthmatics. METHODS: Participants reported symptom control using the
Global Initiative for Asthma criteria at 5 assessments during the 1-year follow
up period. We described variability in the stability of symptom control between
individuals, and used a random-effects logistic regression model to evaluate the
impact of a suite of factors on the stability of symptom control. RESULTS: A
total of 429 individuals (67% female, mean age 51.6) contributed 2141 study
visits. Individuals varied from completely stable in symptom control (18%
remained at the same control level in all 5 visits) to completely unstable (12%
changed the control level between all subsequent visits). Only 4% of between
individual variation in the stability of symptom control was explained by the
included exposures, and a secondary analysis indicated that the history of
symptom control stability was the best predictor of current stability.
CONCLUSIONS: The tendency to remain at a given control level varies significantly
among patients with asthma. Only a small fraction of this variability is
explained by observable characteristics. In the absence of predictors, a previous
history of symptom control stability is the best indicator of future stability
and should be considered when monitoring symptom control.
PMID- 28499774
TI - An Australian Consensus on Infant Feeding Guidelines to Prevent Food Allergy:
Outcomes From the Australian Infant Feeding Summit.
AB - BACKGROUND: Infant feeding in the first postnatal year of life has an important
role in an infant's risk of developing food allergy. Consumer infant feeding
advice is diverse and lacks consistency. AIM: The Australian Infant Feeding
Summit was held with the aim of achieving national consensus on the wording of
guidelines for infant feeding and allergy prevention. METHODS: Two meetings were
hosted by the Centre for Food and Allergy Research, the Australasian Society of
Clinical Immunology and Allergy, and the Australian National Allergy Strategy.
The first meeting of 30 allergy researchers, clinicians, and consumers assessed
the evidence. The second consensus meeting involved 46 expert stakeholders
including state and federal health care agencies, consumers, and experts in
allergy, infant feeding, and population health. RESULTS: Partner stakeholders
agreed on consensus wording for infant feeding advice: CONCLUSIONS: Consensus was
achieved in a context in which there is a high prevalence of food allergy.
Guidelines for other countries are being updated. Provision of consistent wording
related to infant feeding to reduce food allergy risk will ensure clear consumer
advice.
PMID- 28499775
TI - Precision allergy: Separate allergies to male and female dogs.
PMID- 28499776
TI - Seminal plasma hypersensitivity: Clinical and histopathologic features in a
multipara woman.
PMID- 28499778
TI - Fatal Anaphylaxis to Yellow Jacket Stings in Mastocytosis: Options for
Identification and Treatment of At-Risk Patients.
AB - BACKGROUND: Patients with indolent systemic mastocytosis (ISM) are at risk for
severe anaphylactic reactions to yellow jacket (YJ) stings while demonstration of
sensitization can be challenging because specific IgE (sIgE) levels are regularly
below 0.35 kUA/L. The implication of missing YJ allergy is illustrated by a case
of fatal anaphylaxis. OBJECTIVE: To explore the natural course of YJ venom
allergy and the diagnostic accuracy and therapeutic consequence of YJ venom sIgE
in patients with ISM. METHODS: All patients with ISM seen from 1981 to 2015 (n =
243) were evaluated on the number of YJ stings, reaction severity, and
sensitivity and specificity of YJ venom sIgE. YJ venom allergic patients without
mastocytosis served as control (n = 313). RESULTS: A total of 153 patients with
ISM were stung during adult life. The first systemic reaction was more often
severe in patients with ISM than in patients without mastocytosis (69.9% vs
22.0%) and reactions recurred in 40 of 41 re-stung patients with ISM. ISM
reactors showed lower YJ venom sIgE levels than nonmastocytosis reactors (0.61 vs
4.83 kUA/L; P < .001) and asymptomatic sensitization was exceedingly rare. In ISM
the current clinical threshold of 0.35 kUA/L yields a sensitivity and specificity
of 77.6% and 87.5%, respectively. The optimal diagnostic accuracy is achieved at
0.17 kUA/L (sensitivity, 83.6%; specificity, 85.0%). CONCLUSIONS: The high rate
of severe reactions and the fatal case underscore the importance of adequate
diagnostic sensitivity of sIgE in patients with ISM. The sensitivity of sIgE can
be ameliorated by lowering the threshold to 0.17 kUA/L, retaining good
specificity. We recommend sIgE screening in all patients with ISM and discussing
immunotherapy when YJ venom sIgE exceeds 0.17 kUA/L.
PMID- 28499777
TI - Lack of Efficacy of Symptoms and Medical History in Distinguishing the Degree of
Eosinophilia in Nasal Polyps.
AB - BACKGROUND: Distinguishing eosinophilic nasal polyps (NP) from noneosinophilic NP
will impact prognosis and therapeutic responsiveness. OBJECTIVE: To investigate
the ability of clinical history and biomarkers to distinguish these conditions.
METHODS: A total of 74 consecutive patients undergoing surgery for NP were
enrolled. Clinical presentations were evaluated using the 22-item sinonasal
outcome test (SNOT-22). Biomarkers included absolute eosinophil count, IgE, and
extent of tissue hyperplasia on sinus computed tomography scan. Tissue
eosinophilia was quantified in 10 random hpf and data analyzed addressing both
peak and average results. RESULTS: No component of the SNOT-22 was predictive of
tissue eosinophilia. Similarly, a medical history of allergic rhinitis, asthma,
or aspirin-exacerbated respiratory disease was not predictive. An absolute
eosinophil count of more than 300 was associated with NP tissue eosinophilia. In
contrast, neither IgE nor extent of sinus computed tomography hyperplasia was
predictive. CONCLUSIONS: The ability to individualize therapies for NP is
dependent on identifying clinical features or biomarkers of eosinophilia.
However, with the exception of circulating eosinophilia, we could not identify a
clinical feature or biomarker that robustly predicted the presence of tissue
eosinophilia. Even more problematic, even the seeming "criterion standard"
determination of tissue pathology was of limited value, as our cohort displayed a
continuous spectrum of tissue eosinophil expression, making arbitrary any
definitive cutoff distinguishing these conditions.
PMID- 28499779
TI - "Treating Through" Decision and Follow-up in Antibiotic Therapy-Associated
Exanthemas.
AB - BACKGROUND: Immediate discontinuation or replacement of suspected drugs is
considered standard medical care in acute exanthematous skin reactions. In the
treatment of bacterial infections, structurally different alternative
antibiotics, however, are commonly second choice options due to a suboptimal
antimicrobial activity or an unfavorable side effect profile. Nonetheless,
"treating through," the continuation of antibiotic treatment despite an objective
exanthema, is practiced only rarely. OBJECTIVE: We aimed to assess whether
"treating through" is an option for patients with severe bacterial soft tissue
infections (severe cellulitis) who experience maculopapular exanthema (MPE)
during antibiotic therapy. METHODS: We retrospectively reviewed clinical data
from 18 patients who developed MPE within a few days after initiation of
intravenous antibiotic treatment. A decision to "treat through" was made when the
suspected antibiotics (beta-lactams, clindamycin, ciprofloxacin) were clinically
effective and the benefits of continued treatment outweighed potential risks.
Clinical and laboratory findings were closely monitored in an inpatient setting.
RESULTS: In 2 patients, a modification of antibiotic therapy was deemed necessary
due to a significant increase of liver enzymes within 4 days after the initial
decision to "treat through." Because of a progression of MPE under ongoing
treatment with cefuroxime and clindamycin, clindamycin was discontinued in 1
patient. In another 3 patients, antibiotic treatment was modified because of
insufficient improvement of the soft tissue infection. In the remaining 12
"treated through" cases, the skin symptoms improved despite unchanged continued
antibiotic treatment, and relevant laboratory parameters remained within the
normal range. CONCLUSIONS: Careful risk-benefit assessment may enable the
continuation of antibiotic therapy despite MPE, provided that patients are under
close medical observation.
PMID- 28499780
TI - Drug-induced enterocolitis in an adult patient.
PMID- 28499781
TI - Aplastic anemia and cytotoxic T lymphocyte antigen-4 haploinsufficiency treated
with bone marrow transplantation.
PMID- 28499782
TI - Systemic reactions to immunotherapy during mountain cedar season: implications
for seasonal dose adjustment.
PMID- 28499783
TI - CD21 deficiency in 2 siblings with recurrent respiratory infections and
hypogammaglobulinemia.
PMID- 28499784
TI - GSK-3 as a novel prognostic indicator in leukemia.
AB - While leukemias represent a diverse set of diseases with malignant cells derived
from myeloid or lymphoid origin, a common feature is the dysregulation of signal
transduction pathways that influence leukemogeneisis, promote drug resistance,
and favor leukemia stem cells. Mutations in PI3K, PTEN, RAS, or other upstream
regulators can activate the AKT kinase which has central roles in supporting cell
proliferation and survival. A major target of AKT is Glycogen Synthase Kinase 3
(GSK3). GSK3 has two isoforms (alpha and beta) that were studied as regulators of
metabolism but emerged as central players in cancer in the early 1990s. GSK3 is
unique in that the isoforms are constitutively active. Active GSK3 promotes
destruction of oncogenic proteins such as beta Catenin, c-MYC, and MCL-1 and thus
has tumor suppressor properties. In AML, inactivation of GSK3 is associated with
poor overall survival. Interestingly in some leukemias GSK3 targets a tumor
suppressor and thus the kinases can act as tumor promoters in those instances. An
example is GSK3 targeting p27Kip1 in AML with MLL translocation. This review will
cover the role of GSK3 in various leukemias both as tumor suppressor and tumor
promoter. We will also briefly cover current state of GSK3 inhibitors for
leukemia therapy.
PMID- 28499785
TI - Antecedents of basic psychological need satisfaction of pharmacy students: The
role of peers, family, lecturers and workload.
AB - BACKGROUND: Self-determination theory (SDT) provides a model to improve pharmacy
students' well-being or functioning in their study context. According to SDT,
students need a context that satisfies their needs for autonomy, relatedness and
competence in order to function optimally. Contextual factors that could have an
impact on a student's functioning are lecturers, family, peers and workload.
OBJECTIVES: To investigate whether there is a difference between the
contributions family, lecturers, peers and workload make towards the satisfaction
of pharmacy students' basic psychological needs within a university context.
METHODS: An electronic survey was administered amongst students registered with
the North-West University's School of Pharmacy. Registered pharmacy students,
779, completed said electronic survey comprised of a questionnaire on
demographics, BMPN (Balanced Measure of Psychological Needs) and self-developed
ANPNS (Antecedents of Psychological Need-satisfaction Scale). Data derived from
the afore-going was analysed with the aid of structural equation modelling (SEM).
RESULTS: Structural equation modelling explained 46%, 25% and 30% respectively of
the total group's variances in autonomy, competence and relatedness satisfaction,
and 26% of the variance in psychological need frustration. Peers and family
played a significant role in the satisfaction of students' need for autonomy,
relatedness and competence, whilst workload seemingly hampered satisfaction with
regards to relatedness and autonomy. Workload contributed towards frustration
with regards to psychological need satisfaction. The role played by lecturers in
satisfying pharmacy students' need for autonomy, relatedness and competence will
also be highlighted. CONCLUSIONS: This study added to the body of knowledge
regarding contextual factors and the impact those factors have on pharmacy
students' need satisfaction by illustrating that not all factors (family,
lecturers, peers and workload) can be considered equal. Lecturers ought to
recognise the important role family and peers play in the emotional and mental
wellbeing of students and utilise those factors in their teaching. SYNOPSIS: The
mechanism of basic psychological need satisfaction as described in Self
determination theory provide insight into pharmacy students' optimal functioning.
Hence the influence of contextual factors, (lecturers, peers, family and
workload) on the need satisfaction was investigated by means of a survey. The
structural model explained 46%, 25% and 30% of the variances in autonomy,
competence and relatedness satisfaction and 26% of the variance in psychological
need frustration. Family and Peer support contributed the most to the variance
explained of the variables. Lecturers should acknowledge this important role of
family and peers and utilise this premise when they design learning encounters.
PMID- 28499786
TI - Head elevation and lateral head rotation effect on facemask ventilation
efficiency: Randomized crossover trials.
AB - PURPOSE: We performed two prospective randomized crossover trials to evaluate the
effect of head elevation or lateral head rotation to facemask ventilation volume.
METHODS: In the first trial, facemask ventilation was performed with a 12-cm high
pillow (HP) and 4-cm low pillow (LP) in 20 female patients who were scheduled to
undergo general anesthesia. In the second trial, facemask ventilation was
performed with and without lateral head rotation in another 20 female patients.
Ventilation volume was measured in a pressure-controlled ventilation (PCV) manner
at 10, 15, and 20 cmH2O inspiratory pressures. RESULTS: In the first trial
evaluating head elevation effect, facemask ventilation volume was significantly
higher with a HP than with a LP at 15 and 20 cmH2O inspiratory pressure (15
cmH2O: HP median540 [IQR480-605] mL, LP 460 [400-520] mL, P=0.006, 20 cmH2O: HP
705 [650-800] mL, LP 560 [520-677] mL, P<0.001). In the second trial, lateral
head rotation did not significantly increase facemask ventilation volume at all
inspiratory pressure. CONCLUSION: Head elevation increased facemask ventilation
volume in normal airway patients, while lateral head rotation did not.
PMID- 28499787
TI - Motocross-associated head and spine injuries in adult patients evaluated in an
emergency department.
AB - BACKGROUND: Motor vehicle-related injuries (including off-road) are the leading
cause of traumatic brain injury (TBI) and acute traumatic spinal cord injury in
the United States. OBJECTIVES: To describe motocross-related head and spine
injuries of adult patients presenting to an academic emergency department (ED).
METHODS: We performed an observational cohort study of adult ED patients
evaluated for motocross-related injuries from 2010 through 2015. Electronic
health records were reviewed and data extracted using a standardized review
process. RESULTS: A total of 145 motocross-related ED visits (143 unique
patients) were included. Overall, 95.2% of patients were men with a median age of
25years. Sixty-seven visits (46.2%) were associated with head or spine injuries.
Forty-three visits (29.7%) were associated with head injuries, and 46 (31.7%)
were associated with spine injuries. Among the 43 head injuries, 36 (83.7%) were
concussions. Seven visits (16.3%) were associated with at least 1 head
abnormality identified by computed tomography, including skull fracture (n=2),
subdural hematoma (n=1), subarachnoid hemorrhage (n=4), intraparenchymal
hemorrhage (n=3), and diffuse axonal injury (n=3). Among the 46 spine injuries,
32 (69.6%) were acute spinal fractures. Seven patients (4.9%) had clinically
significant and persistent neurologic injuries. One patient (0.7%) died, and 3
patients had severe TBIs. CONCLUSION: Adult patients evaluated in the ED after
motocross trauma had high rates of head and spine injuries with considerable
morbidity and mortality. Almost half had head or spine injuries (or both), with
permanent impairment for nearly 5% and death for 0.7%.
PMID- 28499788
TI - Nocturia and Prevalence of Depressive Symptoms in Japanese Adult Patients With
Type 2 Diabetes Mellitus: The Dogo Study.
AB - OBJECTIVES: No studies have investigated the association between nocturia and
depressive symptoms in patients with type 2 diabetes mellitus. Because nocturia
and depressive symptoms are common in patients with type 2 diabetes, we examined
this association in Japanese patients with type 2 diabetes. METHODS: We studied
762 Japanese patients with type 2 diabetes. A self-administered questionnaire was
used to collect information about the variables under study. The subjects were
divided into 3 groups according to their nocturnal micturition: 1) no nocturia;
2) mild nocturia (1 void per night) and 3) moderate to severe nocturia (2 or more
voids per night). Depressive symptoms were defined as being present when a
subject had a Self-Rating Depression Scale score higher than 49. RESULTS: The
prevalence values of mild nocturia, moderate to severe nocturia and depressive
symptoms were 39.5%, 41.9% and 16.8%, respectively. Both mild nocturia and
moderate to severe nocturia were independently positively associated with
depressive symptoms in all patients; the adjusted ORs were 1.96 (95% CI 1.06 to
3.77) and 2.58 (95% CI 1.38 to 5.04). In female patients, both mild nocturia and
moderate to severe nocturia were independently associated with depressive
symptoms; the adjusted ORs were 5.26 (95% CI 1.73 to 20.61) and 6.91 (95% CI 2.15
to 28.54), respectively. In male patients, neither mild nocturia nor moderate to
severe nocturia was significantly related to depressive symptoms. CONCLUSIONS: In
Japanese female patients with type 2 diabetes, nocturia may be positively
associated with depressive symptoms.
PMID- 28499789
TI - Association Between the Polymorphism of Glu298Asp in Exon 7 of the eNOS Gene With
Foot Ulcer and Oxidative Stress in Adult Patients With Type 2 Diabetes.
AB - OBJECTIVES: Diabetic foot ulcer (DFU) is a common and major manifestation in
patients with diabetes. Oxidative stress (OS) plays an important role in diabetic
complications, such as DFU. Nitric oxide deficiency contributes to the impairment
of diabetic wound healing. The aim of this study was to examine the association
between the eNOS Glu298Asp polymorphism and DFU and oxidative stress in patients
with type 2 diabetes mellitus in an Iranian population. METHODS: In this case
control study, 123 patients with type 2 diabetes and DFU and 134 patients without
DFU were recruited. The genotypes of eNOS Glu298Asp polymorphism in exon 7 were
determined by the polymerase chain reaction-restriction fragment length
polymorphism analysis. We measured the levels of thiobarbituric reactive
substances and ferric-reducing ability of plasma as the potential markers of OS.
RESULTS: There were significant differences in genotype frequencies of eNOS
Glu298Asp polymorphism between case and control groups (GG+TG vs. TT; p=0.002;
OR=0.22, 95% CI 0.83 to 0.62). Also, the frequency of the T allele in cases was
less common than in controls (p=0.004). There was no significant difference in
levels of OS parameters and various genotypes (p>0.05). CONCLUSIONS: These
results imply that the T allele might be protective against DFU.
PMID- 28499790
TI - Trends in Blood Glucose Test Strip Utilization: A Population-Wide Analysis in
Saskatchewan, Canada.
AB - OBJECTIVES: To describe trends in blood glucose test strip (TS) utilization and
cost in Saskatchewan. METHODS: A retrospective analysis of TS use between January
1, 1996, and December 31, 2013, was conducted using population-based health
administrative databases in Saskatchewan. The prescription drug database was used
to describe the annual number of TS dispensations, the number of strips
dispensed, the number of unique beneficiaries and the total costs. A patient
level analysis was also carried out to describe the patterns of TS use (i.e.
light, moderate or heavy) by the entire cohort and by diabetes treatments.
Potential cost savings due to a newly implemented restriction policy were
estimated based on the most recent data (2013). RESULTS: TS utilization increased
dramatically between 1996 and 2013 in terms of the number of users and the
average number of TSs received. The percentage of TS users receiving fewer than 4
TSs per week (i.e. light users) decreased by 20%, while the percentage of heavy
users (i.e. those receiving more than 8 TSs per week) increased by 19%. During
the same period, the use of high-risk oral hypoglycemic medications declined by
30% among all TS users. Heavy TS use was observed in at least one-third of all
users, irrespective of treatment type. CONCLUSIONS: If Saskatchewan's newly
imposed coverage limits had been applied in 2013, the costs of strips exceeding
those limits would have totalled $2.5 million. Although TS use aligns with
chronic disease care paradigms, the substantial costs and lack of evidence of
patient outcomes demand better strategies to help reduce unnecessary use.
PMID- 28499792
TI - Doing More With Less; Are There Some 'Easy Wins' in the Management of Early
Breast Cancer?
PMID- 28499791
TI - The Role of Radiotherapy in Epidermal Growth Factor Receptor Mutation-positive
Patients with Oligoprogression: A Matched-cohort Analysis.
AB - AIMS: Almost all patients with epidermal growth factor receptor (EGFR) mutations
will develop resistance to first-line EGFR tyrosine kinase inhibitors (TKIs). The
management of oligoprogression on EGFR TKI is controversial. Irradiating
progressing tumours may potentially eradicate the resistant clone and allow
continuation of EGFR TKI, but the clinical data remain sparse. We aimed to assess
the effect of radiotherapy on survival outcomes in patients with oligoprogression
in a matched-cohort study. MATERIALS AND METHODS: This was a retrospective
matched-cohort study comparing patients with EGFR mutation-positive stage IV non
small cell lung cancer receiving radiotherapy versus chemotherapy for
progression. Patients in the radiotherapy group received radiotherapy (mainly
stereotactic ablative radiotherapy) for oligoprogression, whereas the
chemotherapy group received only systemic chemotherapy upon progression. Key
prognostic factors including gender, age, performance status, time to first
progression and mutation subtypes were matched. RESULTS: Twenty-five patients
with oligoprogression (radiotherapy group) were identified, and a matched
chemotherapy group with the same number of patients was generated. The median
duration of follow-up was 24.3 and 34 months for the radiotherapy and
chemotherapy groups, respectively. The median overall survival of the
radiotherapy group was significantly longer than the chemotherapy group, 28.2
versus 14.7 months (P = 0.026). The median progression-free survival (PFS) was
7.0 and 4.1 months after radiotherapy and chemotherapy, respectively (P =
0.0017). The use of radiotherapy was an independent predictive factor of overall
survival and PFS in multivariate analysis. Only one patient had >=grade 3
toxicity after radiotherapy. The frequency of secondary T790M mutation and
subsequent Osimertinib exposure were similar in both groups. CONCLUSION:
Radiotherapy may effectively extend EGFR TKI therapy for patients with
oligoprogression on TKI. Improved PFS and overall survival were observed,
although potential biases should not be overlooked. Further randomised studies
are warranted.
PMID- 28499793
TI - Ciprofloxacin-loaded lipid-core nanocapsules as mucus penetrating drug delivery
system intended for the treatment of bacterial infections in cystic fibrosis.
AB - Treatment of bacterial airway infections is essential for cystic fibrosis
therapy. However, effectiveness of antibacterial treatment is limited as bacteria
inside the mucus are protected from antibiotics and immune response. To overcome
this biological barrier, ciprofloxacin was loaded into lipid-core nanocapsules
(LNC) for high mucus permeability, sustained release and antibacterial activity.
Ciprofloxacin-loaded LNC with a mean size of 180nm showed a by 50% increased drug
permeation through mucus. In bacterial growth assays, the drug in the LNC had
similar minimum inhibitory concentrations as the free drug in P. aeruginosa and
S. aureus. Interestingly, formation of biofilm-like aggregates, which were
observed for S. aureus treated with free ciprofloxacin, was avoided by exposure
to LNC. With the combined advantages over the non-encapsulated drug,
ciprofloxacin-loaded LNC represent a promising drug delivery system with the
prospect of an improved antibiotic therapy in cystic fibrosis.
PMID- 28499794
TI - On the role of forces governing particulate interactions in pharmaceutical
systems: A review.
AB - Process understanding for designing, optimizing and scaling of pharmaceutical
unit operations is fundamentally important to address concerns of high risks,
monumental costs, and productivity decline in the pharmaceutical industry. This
is especially important in the rapidly changing landscape of the pharmaceutical
industry. Pharmaceutical processes majorly deal with multiphase, multicomponent
flows, basics of which are discussed in terms of fundamental contact and non
contact forces. Also, basics of multiphase flow regimes, powder flow, and
pertinent process modeling techniques relevant to pharmaceutical unit operations
are discussed. The most fundamental contact and non-contact forces are then
reviewed in detail on their molecular or physical origin, factors which influence
these forces, numerical formalisms and modeling strategies to simulate flows and
processes of pharmaceutical interest.
PMID- 28499796
TI - The antenatal urinary tract dilation classification system accurately predicts
severity of kidney and urinary tract abnormalities.
AB - BACKGROUND: Urinary tract dilation (UTD) is a commonly diagnosed prenatal
condition; however, it is currently unknown which features lead to benign and
resolving or pathologic abnormalities. A consensus UTD classification system
(antenatal UTD classification, UTD-A) was created by Nguyen et al. in 2014 [1],
but has not yet been validated. OBJECTIVE: To evaluate the ability of the UTD-A
system to identify kidney and urinary tract (KUT) abnormalities, assess whether
UTD-A can predict severity of KUT conditions, and perform a cost analysis of
screening ultrasound (US). METHODS: A retrospective single-center study was
conducted at an academic medical center. Inclusion criteria were: neonates in the
well or sick nursery who had a complete abdominal or limited renal US performed
in the first 30 days of life between January 01, 2011 and December 31, 2013. Data
were collected on prenatal US characteristics from which UTD-A classification was
retrospectively applied, and postnatal data were collected up to 2 years
following birth. RESULTS: A total of 203 patients were identified. Of the 36
abnormal postnatal KUT diagnoses, 90% were identified prenatally as UTD A1 or UTD
A2-3. The remaining 10% developed postnatal KUT abnormalities due to
myelomeningocele, such as VUR or UTD, which were not evident prenatally. Overall
sensitivity and specificity of the UTD-A system was 0.767 (95% CI 0.577, 0.901)
and 0.836 (95% CI 0.758, 0.897), respectively, when resolved UTD was counted as a
normal diagnosis. Postnatal diagnoses differed by UTD-A classification as shown
in the Summary fig. Of all the obstructive uropathies, 90.9% occurred in the UTD
A2-3 class and none occurred in UTD-A Normal. Rate of postnatally resolved UTD
was significantly higher in the UTD A1 group (78%) compared with UTD A2-3 (31%)
or UTD-A Normal (12%, all P < 0.001). There was a notable trend towards more UT
surgeries, UTI, and positive VUR among UTD A2-3 patients, but statistical
significance was limited by a small number of patients. CONCLUSIONS: This study
found that the UTD-A classification system revealed important differences in the
severity of UTD abnormalities. With repeated validation in larger cohorts, the
UTD-A classification may be used to offer a prognosis for parents regarding
prenatally diagnosed KUT conditions. Larger prospective studies should be
designed to validate whether the UTD-A system can predict postnatal events
related to UTD morbidity such as need for UT-related surgery or UTI.
PMID- 28499795
TI - Anesthesia-inducing drugs also induce conditioned taste aversions.
AB - Animals learn to reduce their intake of a tastant when its ingestion is followed
by the administration of an anesthesia-inducing drug. To determine the nature of
this intake suppression, the current study examined whether ketamine/xylazine
(Experiment 1) and pentobarbital (Experiment 2) also conditionally reduce taste
palatability. Using lick pattern analysis, we found that pairing saccharin with
either drug reduced total licks, lick cluster size, and initial lick rate. Given
that both lick cluster size and initial lick rate are indices of palatability,
this pattern of results indicates that anesthesia-inducing drugs also induce
conditioned taste aversions.
PMID- 28499797
TI - The S.An.A.(r) concept: Semi-aerobic, Anaerobic, Aerated bioreactor landfill.
AB - Hybrid Bioreactor Landfills are designed to enhance and speed up biological
processes, aiming at reducing the duration of post operational phase until
landfill completion. S.An.A.(r) (Semi-aerobic, Anaerobic, Aerated) concept
consists in a Hybrid Bioreactor featuring a first semi-aerobic phase to enhance
the methane production occurring in the following anaerobic step and a forced
aeration for the abatement of the residual emissions. At the end of the last
step, semi-aerobic conditions are restored and flushing applied for leaching
residual non-biodegradable compounds. Results of the application of S.An.A.(r)
concept to a lab scale bioreactor system showed that pre-aeration was effective
in controlling the concentration of VFA, increasing pH and stimulating methane
production during anaerobic phase; in particular with intermittent airflow the
methane potential was 50% higher respect to control reactors. Forced aeration
reduced organic compounds and nitrogen concentration in leachate of an order of
magnitude, better performing in low airflow reactors. S.An.A.(r) Hybrid
bioreactors proved to be an efficient system both for increasing methane
production and reaching landfill completion in shorter time, suggesting that with
proper landfill management, the duration of post-closure care might be reduced by
25-35%.
PMID- 28499798
TI - Pilot trial on separation conditions for diaper recycling.
AB - By utilizing laboratory-scale tests, the optimal separation conditions for diaper
recycling were identified, and then, these conditions were validated by a pilot
trial. In this research, we determined the mass balances derived during various
processing steps and identified the most feasible procedures to use for
separating each material in the output flow. The results showed that drum
screening was not able to remove all the fiber and super absorbent particles
(SAP) in the plastic-rich fraction and that cellulose enzyme treatment can be a
good solution. To achieve better separation of fibers and SAP, slot screening
followed by a cleaner is a potential option. A feasible diaper recycling process
was recommended based on these results. This process involves screening and
enzymatic treatment for the plastic fraction, and screening, cleaning, and
thickening for the fiber fraction. Treatment procedures were also proposed for
the SAP fraction and rejected materials.
PMID- 28499799
TI - Mouse<->rat aggregation chimaeras can develop to adulthood.
AB - In order to examine interactions between cells originating from different species
during embryonic development we constructed interspecific mouse<->rat chimaeras
by aggregation of 8-cell embryos. Embryos of both species expressed different
fluorescent markers (eGFP and DsRed), which enabled us to follow the fate of both
components from the moment of aggregation until adulthood. We revealed that in
majority of embryos the blastocyst cavity appeared inside the group of rat cells,
while the mouse component was allocated to the deeper layer of the inner cell
mass and to the polar trophectoderm. However, due to rearrangement of all cells
and selective elimination of rat cells, shortly before implantation all primary
lineages became chimaeric. Moreover, despite the fact that rat cells were always
present in the mural trophectoderm, majority of mouse<->rat chimaeric blastocysts
implanted in mouse uterus, and out of those 46% developed into foetuses and pups,
half of which were chimaeric. In contrast to mural trophectoderm, polar
trophectoderm derivatives, i.e. the placentae of all chimaeras were exclusively
of mouse origin. This strongly suggests that the successful postimplantation
development of chimaeras is enabled by gradual elimination of xenogeneic cells
from the nascent placenta. The size of chimaeric newborns was within the limits
of control mouse neonates. The rat component located preferentially in the
anterior part of the body, where it contributed mainly to the neural tube. Our
observations indicate that although chimaeric animals were able to reach
adulthood, high contribution of rat cells tended to diminish their viability.
PMID- 28499800
TI - Improving clinical laboratory performance through quality indicators.
PMID- 28499801
TI - The effect of admission serum potassium levels on in-hospital and long-term
mortality in type A acute aortic dissection.
AB - BACKGROUND: Mild fluctuations in serum potassium (K+) levels are related to the
prognosis of cardiovascular disease. This study aimed to determine the effect of
admission serum potassium levels on in-hospital and long-term mortality in
patients with Stanford type A acute aortic dissection (AAD). MATERIALS AND
METHODS: A total of 588 consecutive patients with type A AAD were enrolled, and
they were grouped according to admission serum potassium level: <3.5, 3.5 to
<4.0, 4.0 to <4.5, 4.5 to <5.0, and >=5.0mmol/L. Clinical outcomes were in
hospital death and long-term all-cause mortality. RESULTS: The in-hospital and
long-term all-cause mortality rates were 10.7% and 16.3%, respectively. A U
shaped relationship was observed between admission serum potassium levels and
both in-hospital death and long-term mortality. Univariate Cox regression
identified potassium levels outside the interval of <3.5 to 4.5mmol/L to be a
risk factor for both in-hospital and long-term death. After adjusting for age,
gender, surgery and other risk factors, potassium levels outside the interval of
<3.5 to 4.5mmol/L still had a significant association with long-term death
[hazard ratio (HR)=1.72, 95% confidence interval (95% CI): 1.07-2.74, P=0.024].
Surgical intervention was the main protective factor associated with both in
hospital (HR=0.01, 95% CI 0.01-0.06, P<0.001) and long-term survival (HR=0.06,
95% CI 0.03-0.12, P<0.001). CONCLUSIONS: Among patients with Stanford type A AAD,
admission serum potassium levels other than 3.5 to 4.5mmol/L might be associated
with an increased risk of in-hospital death and long-term mortality.
PMID- 28499802
TI - AMPK activates FOXO3a and promotes neuronal apoptosis in the developing rat brain
during the early phase after hypoxia-ischemia.
AB - AMP-activated protein kinase (AMPK) is a key metabolic and stress
sensor/effector. Few investigations have been performed to study the role of AMPK
in developing rat brain with hypoxia-ischemia (HI). Forkhead transcriptional
factor (FOXO3a) has been revealed to be a critical effector of AMPK-mediated
celluar apoptosis. However, it is not clear whether AMPK/FOXO3a pathway is
involved in neuronal apoptosis in the developing rat brain after HI. In this
study, we generated hypoxia-ischemia brain damage (HIBD) model using postnatal
day 7 rats. We found that activation of AMPK was accompanied by the decrease of p
mTOR, p-Akt and p-FOXO3a, which induced FOXO3a translocation into the nucleus and
up-regulated the expression of Bim and cleaved caspase 3 (CC3). Furthermore, we
discovered that AMPK inhibition by Compound C, a selective inhibitor for AMPK
activity, significantly increased the phosphorylation levels of mTOR, Akt and
FOXO3a, attenuated the nuclear translocation of FOXO3a, and inhibited Bim and CC3
expression after HI. Moreover, AMPK inhibition reduced cellular apoptosis,
attenuated brain infarct volume and promoted neurological recovery in the
developing rat brain after HI. Our findings suggest that AMPK participates in the
regulation of FOXO3a-mediated neuronal apoptosis in the developing rat brain
after HI. Agents targeting AMPK may offer promise for rescuing neurons from HI
induced damage.
PMID- 28499803
TI - Establishment and characterization of primary astrocyte culture from adult mouse
brain.
AB - As a major class of glial cells, astrocytes have been indicated to play multi
roles in physiological and pathological brain. Astrocyte cultures derived from
postnatal mouse brains have been extensively used to characterize their
biological properties. However, the inability to culture adult mouse primary
astrocytes has long stymied studies of function in adult brain. Here, we
developed a protocol to successfully establish highly enriched astrocyte cultures
from the brains of adult mouse. Cortical tissues were collected to prepare cell
suspension by enzymatic digestion and mechanical dissociation, and then plated
onto vessels pre-coated with gelatin and matrigel and cultured in DMEM medium
containing 20% fetal bovine serum (FBS). Forskolin (FSK) and glial-derived
neurotrophic factor (GDNF) were use to promote astrocyte proliferation and
survival respectively. These adult astrocyte cultures were identified by
immunocytochemical, immunobloting and PCR analysis. Furthermore, biological and
functional analysis indicated that they possess the biochemical and physiological
properties of astrocytes, suggestive of a useful cell model for astroglial
studies in adult brain.
PMID- 28499804
TI - Monckeberg Arteriosclerosis: A Telltale Sign.
AB - Monckeberg arteriosclerosis is often an incidental finding recognized at plain
radiography. It differs from the more common atherosclerosis in that the tunica
intima remains unaffected; hence, the vessel lumen is preserved. Monckeberg
arteriosclerosis is most commonly seen in patients with diabetes and patients
with end-stage renal disease. In this short communication, the author presents a
rare case of Monckeberg arteriosclerosis affecting the facial vasculature.
PMID- 28499806
TI - A Rare Sporadic Case of Camurati-Engelmann Disease With Jaw Involvement.
AB - Camurati-Engelmann disease (CED), or progressive diaphyseal dysplasia, is an
uncommon bone dysplasia that is inherited in an autosomal-dominant pattern. The
disease mainly affects the diaphyses of the long bones but can induce sclerotic
changes to the facial skeleton and skull base. The diagnosis of CED is based on
clinical and radiologic features. This article presents the clinical and
radiologic characteristics of the jaws as visualized on cone-beam computed
tomograms of a 46-year-old woman diagnosed with CED.
PMID- 28499805
TI - Differentiating 131I Radiation Sialadenitis From Autoimmune (Sjogren Syndrome)
Sialadenitis: Case Report.
AB - Radioactive iodine (131I) is used effectively for the treatment of differentiated
thyroid cancers. Because it is actively secreted by the salivary glands,
radiation damage to these glands can occur. Obstructive swellings after mealtime
salivary stimulation are common occurrences. Dry mouth is not usually seen if low
doses of 131I are used. A subjective complaint of xerostomia in a patient treated
with 131I 75.8 mCi proved to be related to the simultaneous presence of Sjogren
syndrome (SS). Serologic, histologic, scintigraphic, and salivary volume findings
and the patient's subjective complaints served to establish the pre-existence of
SS.
PMID- 28499807
TI - Evaluation of insulin-like growth factor (IGF-1) and retinol binding protein (RBP
4) levels in patients with newly diagnosed pancreatic adenocarcinoma (PDAC).
AB - BACKGROUND/OBJECTIVES: The elevation of insulin-like growth factor 1 (IGF-1) and
adipokine retinol-binding protein 4 (RBP-4) is known to be associated with the
risk of many cancers. The aim of this study was to evaluate the serum
concentrations of IGF-1 and RBP-4 in patients with PDAC and chronic pancreatitis
(CP). METHODS: The study included 43 patients with PDAC, 39 patients with CP and
10 controls. The concentrations of IGF-1 and RBP-4 were obtained using the ELISA
method (Corgenix UK Ltd R&D Systems). The study protocol was approved by the
Bioethics Committee at the Medical University of Lodz. RESULTS: In PDAC patients
the serum IGF-1 level was significantly higher than in patients with CP (107.79
+/- 66.40 ng/ml vs 89.91 +/- 74.06 ng/ml; P < 0.05). Patients with both CP and
diabetes mellitus (DM) were noted to have a significantly lower level of IGF-1
compared with those who only had CP (51.33 +/- 24.30 ng/ml vs 108.42 +/- 82.39
ng/ml; P = 0.01). The same result was obtained for men with and without DM (58.05
+/- 32.44 ng/ml vs 98.79 +/- 79.47 ng/ml, P = 0.05). As regards the serum level
of RBP-4, the PDAC and CP groups were not significantly different from each
other. CONCLUSIONS: Diabetes accompanying PDAC does not influence the level of
IGF-1 as opposed to diabetes in the course of CP. The IGF-1 level can be useful
for early diagnosis of PDAC. High concentration of RBP-4 is not specific to
pancreatic cancer, so it does not appear to be a useful biomarker for PDAC.
PMID- 28499808
TI - High-contrast high-resolution imaging of posttraumatic mandibular nerve by 3DAC
PROPELLER magnetic resonance imaging: correlation with the severity of sensory
disturbance.
AB - OBJECTIVE: Magnetic resonance neurography reveals abnormal morphologies of
regenerated nerves and overgrown connective tissue in injured trigeminal nerves,
suggesting neuroma formation. We hypothesized that such deformities and scar
formation contribute to pain symptoms. STUDY DESIGN: High-contrast high
resolution magnetic resonance imaging was utilized to evaluate the inferior
alveolar nerve and lingual nerve following traumatic injury in 19 patients. The
relationship between the morphologic classification and severity of the sensory
disorder was assessed. RESULTS: In all cases, 3-dimensional anisotropy contrast
periodically rotated overlapping parallel lines with enhanced reconstruction
(3DAC-PROPELLER) successfully revealed the inner structures within the lesion.
The isolated type represented the normal course of the nerve isolated from scar
like tissue (8 cases), whereas the deformity type included the deformed nerve
either within scar-like tissue or by itself, unassociated with surrounding scar
like tissue (9 cases). In the remaining 2 cases, the nerve tissue and scar-like
tissue were incorporated. Patients with the deformity type exhibited
significantly more severe pain symptoms compared with patients with the isolated
type. CONCLUSIONS: Overgrown connective tissue does not necessarily block
regenerating nerves and itself may not cause pain. The morphologic findings on
the 3DAC-PROPELLER were relevant to the severity of pain symptoms.
PMID- 28499810
TI - Prevalence of late-onset pompe disease in Portuguese patients with diaphragmatic
paralysis - DIPPER study.
AB - : Pompe disease is a rare autosomal recessive neuromuscular disorder caused by
acid alpha-glucosidase enzyme (GAA) deficiency and divided into two distinct
variants, infantile- and late-onset. The late-onset variant is characterized by a
spectrum of phenotypic variation that may range from asymptomatic, to reduced
muscle strength and/or diaphragmatic paralysis. Since muscle strength loss is
characteristic of several different conditions, which may also cause
diaphragmatic paralysis, a protocol was created to search for the diagnosis of
Pompe disease and exclude other possible causes. METHODS: We collected a sample
size of 18 patients (10 females, 8 males) with a median age of 60 years and
diagnosis of diaphragmatic paralysis of unknown etiology, followed in the
Pulmonology outpatient consultation of 9 centers in Portugal, over a 24-month
study period. We evaluated data from patient's clinical and demographic
characteristics as well as complementary diagnostic tests including blood tests,
imaging, neurophysiologic and respiratory function evaluation. All patients were
evaluated for GAA activity with DBS (dried blood test) or serum quantification
and positive results confirmed by serum quantification and sequencing. RESULTS:
Three patients were diagnosed with Pompe's disease and recommended for enzyme
replacement therapy. The prevalence of Pompe, a rare disease, in our
diaphragmatic paralysis patient sample was 16.8%. CONCLUSION: We conclude that
DBS test for GAA activity should be recommended for all patients with
diaphragmatic paralysis which, despite looking at all the most common causes,
remains of unknown etiology; this would improve both the timing and accuracy of
diagnosis for Pompe disease in this patient population. Accurate diagnosis will
lead to improved care for this rare, progressively debilitating but treatable
neuromuscular disease.
PMID- 28499811
TI - The effect of lever height on the microstructure of operant behavior.
AB - The effect of lever height on the temporal organization of reinforced lever
pressing was examined. Lever pressing was reinforced on a variable-interval 30-s
schedule in rats, with lever height manipulated across six successive conditions.
Parameters of the organization of responses in bouts (bout length distribution,
bout-initiation rate, within-bout rate, and sequential dependency) were
estimated. These estimates revealed (1) a qualitative change in the distribution
of IRTs and their sequential dependency when the lever was too high, (2) a
mixture of geometrically-distributed bout lengths at all lever heights, and (3)
longer bouts at lower and intermediate lever heights. In accordance with previous
data, these findings suggest that lower and intermediate lever heights favored
lever pressing with longer bout lengths, faster bout initiation, faster within
bout responding, and more sequentially dependent timing. These results underscore
the disociability of motoric capacity in operant performance, and may reflect the
influence of the body size on the temporal organization of the operant.
PMID- 28499809
TI - An emerging role for the lateral habenula in aggressive behavior.
AB - Inter-male aggression is an essential component of social behavior in organisms
from insects to humans. However, when expressed inappropriately, aggression poses
significant threats to the mental and physical health of both the aggressor and
the target. Inappropriate aggression is a common feature of numerous
neuropsychiatric disorders in humans and has been hypothesized to result from the
atypical activation of reward circuitry in response to social targets. The
lateral habenula (LHb) has recently been identified as a major node of the
classical reward circuitry and inhibits the release of dopamine from the midbrain
to signal negative valence. Here, we discuss the evidence linking LHb function to
aggression and its valence, arguing that strong LHb outputs to the ventral
tegmental area (VTA) and the dorsal raphe nucleus (DRN) are likely to play roles
in aggression and its rewarding components. Future studies should aim to
elucidate how various inputs and outputs of the LHb shape motivation and reward
in the context of aggression.
PMID- 28499812
TI - Modeling of the interaction between grip force and vibration transmissibility of
a finger.
AB - It is known that the vibration characteristics of the fingers and hand and the
level of grip action interacts when operating a power tool. In the current study,
we developed a hybrid finger model to simulate the vibrations of the hand-finger
system when gripping a vibrating handle covered with soft materials. The hybrid
finger model combines the characteristics of conventional finite element (FE)
models, multi-body musculoskeletal models, and lumped mass models. The distal,
middle, and proximal finger segments were constructed using FE models, the finger
segments were connected via three flexible joint linkages (i.e., distal
interphalangeal joint (DIP), proximal interphalangeal joint (PIP), and
metacarpophalangeal (MCP) joint), and the MCP joint was connected to the ground
and handle via lumped parameter elements. The effects of the active muscle forces
were accounted for via the joint moments. The bone, nail, and hard connective
tissues were assumed to be linearly elastic whereas the soft tissues, which
include the skin and subcutaneous tissues, were considered as hyperelastic and
viscoelastic. The general trends of the model predictions agree well with the
previous experimental measurements in that the resonant frequency increased from
proximal to the middle and to the distal finger segments for the same grip force,
that the resonant frequency tends to increase with increasing grip force for the
same finger segment, especially for the distal segment, and that the magnitude of
vibration transmissibility tends to increase with increasing grip force,
especially for the proximal segment. The advantage of the proposed model over the
traditional vibration models is that it can predict the local vibration behavior
of the finger to a tissue level, while taking into account the effects of the
active musculoskeletal force, the effects of the contact conditions on
vibrations, the global vibration characteristics.
PMID- 28499813
TI - Red blood cell aggregate flux in a bifurcating microchannel.
AB - Red blood cell aggregation plays a key role in microcirculatory flows, however,
little is known about the transport characteristics of red blood cell aggregates
in branching geometries. This work reports on the fluxes of red blood cell
aggregates of various sizes in a T-shaped microchannel, aiming to clarify the
effects of different flow conditions in the outlet branches of the channel. Image
analysis techniques, were utilised, and moderately aggregating human red blood
cell suspensions were tested in symmetric (~50-50%) and asymmetric flow splits
through the two outlet (daughter) branches. The results revealed that the flux
decreases with aggregate size in the inlet (parent) and daughter branches, mainly
due to the fact that the number of larger structures is significantly smaller
than that of smaller structures. However, when the flux in the daughter branches
is examined relative to the aggregate size flux in the parent branch an increase
with aggregate size is observed for a range of asymmetric flow splits. This
increase is attributed to size distribution and local concentration changes in
the daughter branches. The results show that the flow of larger aggregates is not
suppressed downstream of a bifurcation, and that blood flow is maintained, for
physiological levels of red blood cell aggregation.
PMID- 28499814
TI - Selected cholesterol biosynthesis inhibitors produce accumulation of the
intermediate FF-MAS that targets nucleus and activates LXRalpha in HepG2 cells.
AB - Sterol intermediates of the cholesterol biosynthetic pathway have drawn attention
for novel biological activities. Follicular fluid meiosis activating sterol (FF
MAS) is a LXRalpha ligand and a potential modulator of physiologic processes
regulated by nuclear receptors, such as lipid homeostasis and cell proliferation.
In this work, we established a model to selectively accumulate FF-MAS in HepG2
cells, by using a combination of the inhibitors AY9944 and 17-hydroxyprogesterone
to block C14-sterol reductases and the downstream C4-demethylase complex. We
investigated the effects produced by altered levels of cholesterol biosynthesis
intermediates, in order to dissect their influence on LXRalpha signaling. In
particular, endogenously accumulated FF-MAS was able to modulate the expression
of key genes in cholesterol metabolism, to activate LXRalpha nuclear signaling
resulting in increased lipogenesis, and to inhibit HepG2 cells proliferation.
Moreover, a fluorescent ester derivative of FF-MAS localized in nuclear lipid
droplets, suggesting a role for these organelles in the storage of signaling
lipids interacting with nuclear partners.
PMID- 28499815
TI - New insight into the interaction of TRAF2 C-terminal domain with lipid raft
microdomains.
AB - In this study we provide the first evidence of the interaction of a truncated
TRAF2 with lipid raft microdomains. We have analyzed this interaction by
measuring the diffusion coefficient of the protein in large and giant unilamellar
vesicles (LUVs and GUVs, respectively) obtained both from synthetic lipid
mixtures and from natural extracts. Steady-state fluorescence measurements
performed with synthetic vesicles indicate that this truncated form of TRAF2
displays a tighter binding to raft-like LUVs with respect to the control (POPC
containing LUVs), and that this process depends on the protein oligomeric state.
Generalized Polarization measurements and spectral phasor analysis revealed that
truncated-TRAF2 affects the membrane fluidity, especially when vesicles are
heated up at physiological temperature. The addition of nanomolar concentration
of TRAF2 in GUVs also seems to exert a mechanical action, as demonstrated by the
formation of intraluminal vesicles, a process in which ganglioside GM1 plays a
crucial role.
PMID- 28499816
TI - Tumor ablation using low-intensity ultrasound and sound excitable drug.
AB - The cell membrane is a semi-fluid container that defines the boundary of cells,
and provides an enclosed environment for vital biological processes. A sound
excitable drug (SED) that is non-cytotoxic to cells is developed to disrupt the
plasma membrane under gentle ultrasound insonation, 1MHz, 1W/cm2. The frequency
and power density of insonation are within the physical therapy and medical
imaging windows; thus the applied ultrasound is safe and not harmful to tissues.
The insertion of SEDs into the plasma membrane is not toxic to cells; however,
the intruding SEDs weaken the membrane's integrity. Under insonation, the
ultrasound energy destabilized the SED disrupted membranes, resulting in membrane
rupture and eventual cell death. In a xenograft breast tumor model, the SED alone
or the ultrasound alone caused little adverse effects to tumor tissue, while the
combined treatment triggered necrosis with a brief local insonation of 3min. The
described sono-membrane rupture therapy could be a safe alternative to the
currently used high-energy tissue ablation technology, which uses X-rays, gamma
rays, electron beams, protons, or high-intensity focused ultrasound.
PMID- 28499817
TI - Use of CellNetAnalyzer in biotechnology and metabolic engineering.
AB - Mathematical models of the cellular metabolism have become an essential tool for
the optimization of biotechnological processes. They help to obtain a systemic
understanding of the metabolic processes in the used microorganisms and to find
suitable genetic modifications maximizing the production performance. In
particular, methods of stoichiometric and constraint-based modeling are
frequently used in the context of metabolic and bioprocess engineering. Since
metabolic networks can be complex and comprise hundreds or even thousands of
metabolites and reactions, dedicated software tools are required for an efficient
analysis. One such software suite is CellNetAnalyzer, a MATLAB package providing,
among others, various methods for analyzing stoichiometric and constraint-based
metabolic models. CellNetAnalyzer can be used via command-line based operations
or via a graphical user interface with embedded network visualizations. Herein we
will present key functionalities of CellNetAnalyzer for applications in
biotechnology and metabolic engineering and thereby review constraint-based
modeling techniques such as metabolic flux analysis, flux balance analysis, flux
variability analysis, metabolic pathway analysis (elementary flux modes) and
methods for computational strain design.
PMID- 28499818
TI - Biosurfactant-biopolymer driven microbial enhanced oil recovery (MEOR) and its
optimization by an ANN-GA hybrid technique.
AB - A lipopeptide biosurfactant produced by marine Bacillus megaterium and a
biopolymer produced by thermophilic Bacillus licheniformis were tested for their
application potential in the enhanced oil recovery. The crude biosurfactant
obtained after acid precipitation effectively reduced the surface tension of
deionized water from 70.5 to 28.25mN/m and the interfacial tension between lube
oil and water from 18.6 to 1.5mN/m at a concentration of 250mgL-1. The
biosurfactant exhibited a maximum emulsification activity (E24) of 81.66% against
lube oil. The lipopeptide micelles were stabilized by addition of Ca2+ ions to
the biosurfactant solution. The oil recovery efficiency of Ca2+ conditioned
lipopeptide solution from a sand-packed column was optimized by using artificial
neural network (ANN) modelling coupled with genetic algorithm (GA) optimization.
Three important parameters namely lipopeptide concentration, Ca2+ concentration
and solution pH were considered for optimization studies. In order to further
improve the recovery efficiency, a water soluble biopolymer produced by Bacillus
licheniformis was used as a flooding agent after biosurfactant incubation. Upon
ANN-GA optimization, 45% tertiary oil recovery was achieved, when biopolymer at a
concentration of 3gL-1 was used as a flooding agent. Oil recovery was only 29% at
optimal conditions predicted by ANN-GA, when only water was used as flooding
solution. The important characteristics of biopolymers such as its viscosity,
pore plugging capabilities and bio-cementing ability have also been tested. Thus,
as a result of biosurfactant incubation and biopolymer flooding under the optimal
process conditions, a maximum oil recovery of 45% was achieved. Therefore, this
study is novel, timely and interesting for it showed the combined influence of
biosurfactant and biopolymer on solubilisation and mobilization of oil from the
soil.
PMID- 28499819
TI - Correction to Lancet Glob Health 2017; published online April 30,
http://dx.doi.org/10.1016/S2214-109X(17)30196-1.
PMID- 28499820
TI - HE4 expression in lung cancer, a meta-analysis.
AB - BACKGROUND: The prognostic role of Human epididymis protein 4 (HE4) expression in
lung cancer remains controversial. We performed this meta-analysis to assess the
prognostic value of HE4 expression in lung cancer. METHODS: A systematic
literature search was conducted to identify eligible studies in PubMed, Embase
and Wanfang databases. The pooled hazard ratios (HRs) and their 95% confidence
intervals (CIs) were used to assess the relationship. RESULTS: A total of 1412
patients from 8 studies were included in this meta-analysis. The results of
univariate analysis (HR=1.73, 95% CI: 1.19-2.52, P=0.004) and multivariate
analysis (HR=2.49, 95% CI: 1.89-3.28, P<0.001) demonstrated that high HE4
expression in lung cancer patients was correlated with poor overall survival
(OS). We observed through further stratified analysis of the results of the
univariate analysis that high HE4 expression was associated with worse OS in
Asian lung cancer patients (HR=2.48, 95% CI: 1.88-3.26, P<0.001). However, there
was no significant association between high HE4 expression and poor OS in
Caucasian patients (HR=1.12, 95% CI: 0.80-1.55, P=0.513). CONCLUSION: High serum
HE4 level was a marker of poor prognosis in lung cancer patients, particularly in
Asian patients with lung cancer.
PMID- 28499821
TI - X-ray crystal structure of rivoglitazone bound to PPARgamma and PPAR subtype
selectivity of TZDs.
AB - Thiazolidinedione (TZD) compounds targeting the nuclear receptor peroxisome
proliferator-activated receptor gamma (PPARgamma) demonstrate unique benefits for
the treatment of insulin resistance and type II diabetes. TZDs include
rosiglitazone, pioglitazone and rivoglitazone, with the latter being the most
potent. The TZDs are only marginally selective for the therapeutic target
PPARgamma as they also activate PPARalpha and PPARdelta homologues to varying
degrees, causing off-target effects. While crystal structures for TZD compounds
in complex with PPARgamma are available, minimal structural information is
available for TZDs bound to PPARalpha and PPARdelta. This paucity of structural
information has hampered the determination of precise structural mechanisms
involved in TZD selectivity between PPARs. To help address these questions
molecular dynamic simulations were performed of rosiglitazone, pioglitazone and
rivoglitazone in complex with PPARalpha, PPARdelta, and PPARgamma in order to
better understand the mechanisms of PPAR selectivity. The simulations revealed
that TZD interactions with residues Tyr314 and Phe318 of PPARalpha and residues
Phe291 and Thr253 of PPARdelta as well as the omega loop, are key determinants of
TZD receptor selectivity. Notably, in this study, we solve the first X-ray
crystal structure of rivoglitazone bound to any PPAR. Rivoglitazone forms a
unique hydrogen bond network with the residues of the PPARgamma co-activator
binding surface (known as AF2) and makes more extensive contacts with helix 3 and
the beta-sheet as compared to model TZD compounds such as rosiglitazone.
PMID- 28499822
TI - Activation of STAT3/HIF-1alpha/Hes-1 axis promotes trastuzumab resistance in HER2
overexpressing breast cancer cells via down-regulation of PTEN.
AB - BACKGROUND: Resistance to the HER2-targeted antibody trastuzumab remains to be a
major clinical challenge in the treatment of HER2-positive breast cancer. Hyper
activation of STAT3 is proposed to be a predictive biomarker of trastuzumab
resistance. However, the precise mechanism(s) remains poorly defined. Evidence is
emerging that HIF-1alpha, a central downstream element of STAT3 pathway, serves a
pivotal role in the complex signaling network with subsequent diverse cellular
events. MATERIAL AND METHODS: We have established trastuzumab resistant SKBR3
cells (SKBR3-TR). The cell viability, apoptosis as well as western blot, siRNA
transfection and co-immunoprecipitation assays were performed to evaluate the
involvement of STAT3/HIF-1alpha in modulation of trastuzumab resistance. RESULTS:
We found that in SKBR3-TR cells and conditioned medium-treated parental cells,
constitutive phosphorylated STAT3 coincided with prominent up-regulation of HIF
1alpha which was accompanied with PTEN attenuation. Moreover, the inhibition of
STAT3 activation by Stattic and/or genetically STAT3 knocking down decreased HIF
1alpha level in SKBR3-TR cells. Additionally, treatment with Stattic and/or STAT3
siRNA engendered the up-regulation of PTEN protein in STAT3-inhibited resistant
cells. Restoration of PTEN was also observed following siRNA-mediated silencing
of HIF-1alpha expression. Moreover, down-regulation of HIF-1alpha caused a
reduction in the HES-1 content. Further study with HES-1 specific siRNA revealed
the elevation of PTEN expression in HES-1 knock-down trastuzumab resistant cells.
CONCLUSION: The impairment of STAT3-HIF-1alpha-HES-1 pathway restored trastuzumab
sensitivity through up-regulation of PTEN protein. GENERAL SIGNIFICANCE: These
findings highlighted the signal integrator role of HIF-1alpha in STAT3-mediated
trastuzumab resistance induction which would be valuable in designing more
efficient chemosensitization strategies.
PMID- 28499823
TI - Structural and mechanistic insights into Mycothiol Disulphide Reductase and the
Mycoredoxin-1-alkylhydroperoxide reductase E assembly of Mycobacterium
tuberculosis.
AB - Mycobacteria employ a versatile machinery of the mycothiol-dependent system,
containing the proteins mycothiol disulfide reductase (Mtr), the oxido-reductase
Mycoredoxin-1 (Mrx-1) and the alkyl-hydroperoxide subunit E (AhpE). The mycothiol
dependent protein ensemble regulates the balance of oxidized-reduced mycothiol,
to ensure a reductive intracellular environment for optimal functioning of its
proteins even upon exposure to oxidative stress. Here, we determined the first
low-resolution solution structure of Mycobacterium tuberculosis Mtr (MtMtr)
derived from small-angle X-ray scattering data, which provides insight into its
dimeric state. The solution shape reveals the two NADPH-binding domains inside
the dimeric MtMtr in different conformations. NMR-titration shows that the MtMtr
MtMrx-1 interaction is characterized by a fast exchange regime and critical
residues involved in the protein-protein interaction were identified. Using NMR
spectroscopy and docking studies, the epitopes of MtMrx-1 and MtAhpE interaction
are described, shedding new light into the interaction interface and mechanism of
action. Finally, the essential residue of MtMrx-1 identified in the interaction
with MtMtr and MtAhpE form a platform for structure-guided drug design against
the versatile enzyme machinery of the mycothiol-dependent system inside M.
tuberculosis.
PMID- 28499824
TI - Quantifying dietary exposure to pesticide residues using spraying journal data.
AB - Relatively few studies are available on the combined risk of realistic dietary
pesticide exposure. Despite available studies showing low risk, public concern
remains. Recent methods used to estimate realistic exposure levels have a number
of drawbacks, and better methods are needed. Using a novel approach, we estimated
the combined exposure in the Danish population, resulting from pesticide usage in
Danish agriculture. The complete Danish spraying journal data from 2014, and
supervised trial residue levels reported by EFSA, were used in combination,
generating residue estimates in 25 crops. Cumulative risk assessments were made
for six typical Danish consumer diets. In terms of intake of cereals, sugar,
fruits and vegetables, the 25 crops included accounted 70% of the diets of Danish
consumers. The Hazard Index (HI) method was used to assess the consumer risk.
Despite the conservative (cautious) approach, low HI values where obtained.
Highest HI was 14% of the Acceptable Daily Intake (ADI) for Children. The main
advantages of the new exposure estimation method are 1) comprehensive use data
not relying on random samples, 2) coverage of all pesticides used, and 3) more
precise estimates of residues that are below the standard reporting limits in the
national monitoring program.
PMID- 28499825
TI - Induction of cytochrome P450-dependent mixed function oxidase activities and
peroxisome proliferation by chloramine-T in male rat liver.
AB - Chloramine-T is an antimicrobial agent recognized for its disinfectant properties
widely used in food industry. As an N-chloro-compound, chloramine-T contains
electrophilic chlorine and in water it hydrolyses to hypochlorite. Chlorine as
hypochlorous acid or hypochlorite is a very reactive chemical which can function
as both an oxidant and halogenating agent. Because chloramine-T could be involved
in the metabolic activation of drugs, in the present study the effects of
chloramine-T on the activities of some drug metabolizing enzymes in rat liver
microsomes and peroxisome proliferation were determined in vivo. Rats were
treated orally with chloramine-T at doses of 1.25, 2.50, 5 and 10 mg/kg body
weight (bw)/day for 6 days. The activities of CYP2E1, CYP1A1/2 CYP2B1/2, CYP3A4
and CYP4A1/2 enzymes significantly increased after treatment with 2.50, 5 and 10
mg/kg bw/day, in a dose-dependent manner as compared to control. This effect was
not observed after chloramine-T treatment at dose of 1.25 mg/kg bw/day. Our
results suggest that chloramine-T may potentiate the toxicity of many xenobiotics
via metabolic activation and/or accumulation of reactive metabolites.
PMID- 28499826
TI - RIFM fragrance ingredient safety assessment, 5-Acetyl-3-isopropyl-1,1,2,6
tetramethylindane, CAS Registry Number 68140-48-7.
PMID- 28499827
TI - Drug-resistant tuberculosis threatens WHO's End-TB strategy.
PMID- 28499829
TI - Characteristics of traditional Chinese medicine usage in children with precocious
puberty: A nationwide population-based study.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Precocious puberty (PP) occurs in children with
the early onset of pubertal development leading to physical and psychological
problems. Current medical treatment is expensive and has its side effects.
However, little is known about the utilization of traditional Chinese medicine
(TCM) among patients with PP. To characterize the application of TCM among these
patients, we conducted a nationwide population-based study. MATERIALS AND
METHODS: We used the Taiwanese National Health Insurance Research Database
(NHIRD), to perform a nationwide population-based study. The NHIRD has a derived
dataset with the information for a randomly selected half of all insured children
from 1997 to 2008 in Taiwan. We identified children <18 years of age with newly
diagnosed sexual precocity (ICD-9 CM code: 259.1). The subjects were categorized
based on the inclusion of TCM in their treatment plan. RESULTS: Overall, 3495
newly diagnosed subjects with sexual precocity were included. Among these
children, 1.86% (N=65) had used TCM. There were significantly more subjects with
no treatment, 87.32% (N=3052), than those with treatment of TCM, western
medicine, or both. Most of the TCM users received Chinese herbal remedies
(98.25%), and only 1.75% received acupuncture or manipulative therapies. Zhi-Bai
Di-Huang-Wan was the most frequently prescribed TCM formulation (23.73%), while
Mai-Ya (Fructus Hordei Germinatus) was the most commonly prescribed single herb
(10.87%). CONCLUSION: Our study identified the characteristics and prescription
patterns of TCM for children with PP in Taiwan. Further basic mechanistic studies
and clinical trials are needed to confirm the efficacy and mechanism.
PMID- 28499828
TI - Estimating the future burden of multidrug-resistant and extensively drug
resistant tuberculosis in India, the Philippines, Russia, and South Africa: a
mathematical modelling study.
AB - BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR)
tuberculosis are emerging worldwide. The Green Light Committee initiative
supported programmatic management of drug-resistant tuberculosis in 90 countries.
We used estimates from the Preserving Effective TB Treatment Study to predict MDR
and XDR tuberculosis trends in four countries with a high burden of MDR
tuberculosis: India, the Philippines, Russia, and South Africa. METHODS: We
calibrated a compartmental model to data from drug resistance surveys and WHO
tuberculosis reports to forecast estimates of incident MDR and XDR tuberculosis
and the percentage of incident MDR and XDR tuberculosis caused by acquired drug
resistance, assuming no fitness cost of resistance from 2000 to 2040 in India,
the Philippines, Russia, and South Africa. FINDINGS: The model forecasted the
percentage of MDR tuberculosis among incident cases of tuberculosis to increase,
reaching 12.4% (95% prediction interval 9.4-16.2) in India, 8.9% (4.5-11.7) in
the Philippines, 32.5% (27.0-35.8) in Russia, and 5.7% (3.0-7.6) in South Africa
in 2040. It also predicted the percentage of XDR tuberculosis among incident MDR
tuberculosis to increase, reaching 8.9% (95% prediction interval 5.1-12.9) in
India, 9.0% (4.0-14.7) in the Philippines, 9.0% (4.8-14.2) in Russia, and 8.5%
(2.5-14.7) in South Africa in 2040. Acquired drug resistance would cause less
than 30% of incident MDR tuberculosis during 2000-40. Acquired drug resistance
caused 80% of incident XDR tuberculosis in 2000, but this estimate would decrease
to less than 50% by 2040. INTERPRETATION: MDR and XDR tuberculosis were forecast
to increase in all four countries despite improvements in acquired drug
resistance shown by the Green Light Committee-supported programmatic management
of drug-resistant tuberculosis. Additional control efforts beyond improving
acquired drug resistance rates are needed to stop the spread of MDR and XDR
tuberculosis in countries with a high burden of MDR tuberculosis. FUNDING: US
Agency for International Development and US Centers for Disease Control and
Prevention, Division of Tuberculosis Elimination.
PMID- 28499830
TI - Implementation of a systematic culturing program to monitor the efficacy of
endoscope reprocessing: outcomes and costs.
AB - BACKGROUND AND AIMS: In 2015, the U.S. Food and Drug Administration and Centers
for Disease Control and Prevention (CDC) issued guidance for duodenoscope
culturing and reprocessing in response to outbreaks of carbapenem-resistant
Enterobacteriaceae (CRE) duodenoscope-related infections. Based on this guidance,
we implemented best practices for reprocessing and developed a systematic process
for culturing endoscopes with elevator levers. The aim of this study is to report
the outcomes and direct costs of this program. METHODS: First, clinical
microbiology data from 2011 to 2014 were reviewed retrospectively to assess for
possible elevator lever-equipped endoscope-related CRE infections. Second, a
program to systematically culture elevator lever-equipped endoscopes was
implemented. Each week, about 25% of the inventory of elevator lever-equipped
endoscopes is cultured based on the CDC guidelines. If any cultures return
bacterial growth, the endoscope is quarantined pending repeat culturing. The
costs of the program, including staff time and supplies, have been calculated.
RESULTS: From 2011 to 2014, none of 17 patients with documented CRE infection had
undergone ERCP or endoscopic ultrasound in the previous 36 months. From June 2015
to September 2016, 285 cultures were performed. Three (1.1%) had bacterial
growth, 2 with skin contaminants and 1 with an oral contaminant. The associated
endoscopes were quarantined and reprocessed, and repeat cultures were negative.
The total estimated cost of our program for an inventory of 20 elevator lever
equipped endoscopes was $30,429.60 per year ($1521.48 per endoscope).
CONCLUSIONS: This 16-month evaluation of a systematic endoscope culturing program
identified a low rate of positive cultures after elevator lever endoscope
reprocessing. All positive cultures were with non-enteric microorganisms. The
program was of modest cost and identified reprocessing procedures that may have
led to a low rate of positive cultures.
PMID- 28499831
TI - Resolution of hypertropia with correction of consecutive horizontal deviation.
AB - BACKGROUND: To study the resolution of hypertropia in patients who undergo
horizontal deviation surgery for consecutive esotropia or consecutive exotropia.
METHODS: We retrospectively reviewed the records of 23 patients with consecutive
esotropia or exotropia who had concomitant vertical tropia. All patients had had
surgery for horizontal deviation that required further surgery to correct
consecutive horizontal strabismus and had a minimum of six months of
postoperative follow-up. All patients were noted to have vertical deviation
greater than 5 prism diopters (PD) in primary position on preoperative
examination. Patients underwent corrective surgery for horizontal strabismus
without surgical manipulation of the vertical extraocular muscles. The exclusion
criteria were coexisting oblique muscle dysfunction, manifest or latent
dissociated vertical deviation, and extraocular muscle palsy. RESULTS: The mean
preoperative vertical deviations were 7.6 +/- 2.3 PD for distance and 7.3 +/- 2.3
PD for near. All patients had resolution of vertical deviation in all fields of
gaze despite surgical correction only being made to horizontal extraocular
muscles. No patients had measureable vertical tropia during six months of follow
up. CONCLUSION: We propose that measureable hypertropia unrelated to oblique
muscle dysfunction, dissociated vertical deviation, or paretic/mechanical muscle
that coincides with consecutive horizontal deviation can be resolved with
horizontal muscle surgery alone. Therefore, it may not be necessary to perform
vertical surgery to correct coincident vertical deviation in patients with
consecutive horizontal deviation. More research is needed in the form of
prospective clinical trials to determine whether vertical surgery has any utility
for these patients.
PMID- 28499832
TI - Versatile and precise gene-targeting strategies for functional studies in
mammalian cell lines.
AB - The advent of programmable nucleases such as ZFNs, TALENs and CRISPR/Cas9 has
brought the power of genetic manipulation to widely used model systems. In
mammalian cells, nuclease-mediated DNA double strand break is mainly repaired
through the error-prone non-homologous end-joining (NHEJ) repair pathway,
eventually leading to accumulation of small deletions or insertions (indels) that
can inactivate gene function. However, due to the variable size of the indels and
the polyploid status of many cell lines (e.g., cancer-derived cells), obtaining a
knockout usually requires lengthy screening and characterization procedures.
Given the more precise type of modifications that can be introduced upon homology
directed repair (HDR), we have developed HDR-based gene-targeting strategies that
greatly facilitate the process of knockout generation in cell lines. To generate
reversible knockouts (R-KO), a selectable promoter-less STOP cassette is inserted
in an intron, interrupting transcription. Loss-of-function can be validated by RT
qPCR and is removable, enabling subsequent restoration of gene function. A
variant of the R-KO procedure can be used to introduce point mutations. To
generate constitutive knockouts (C-KO), an exon is targeted, which makes use of
HDR-based gene disruption together with NHEJ-induced indels on non-HDR targeted
allele(s). Hence the C-KO procedure greatly facilitates simultaneous inactivation
of multiple alleles. Overall these genome-editing tools offer superior precision
and efficiency for functional genetic approaches. We provide detailed protocols
guiding in the design of targeting vectors and in the analysis and validation of
gene targeting experiments.
PMID- 28499835
TI - Increase of reactive oxygen species generation in cerebral cortex slices after
the transiently enhanced metabolic activity.
AB - Under certain conditions such as hypoxia-reoxygenation, the generation of
reactive oxygen species (ROS) increases following hypoxia caused by a decreased
oxygen supply. As another hypoxic condition, an excess neural activity status
including epileptic seizure induces a decrease in tissue oxygen partial pressure
(pO2) caused by enhanced oxygen utilization; however, whether ROS generation
increases following the hypoxic status induced by transiently enhanced energy
metabolism in brain tissue currently remains unknown. We herein investigated ROS
dependent chemiluminescence in cerebral cortex slices during the restoration of
transiently enhanced energy metabolism induced by a high-potassium treatment with
tissue pO2 changes and redox balance. ROS generation in the tissue was enhanced
after high-potassium-induced hypoxia, but not by the reversed order of the
treatment: control-potassium then high-potassium treatment, high-potassium
treatment alone, and control-potassium treatment alone. The high-potassium
treatment induced a transient decrease in tissue pO2 and a shift in the tissue
redox balance towards reduction. The transient shift in the tissue redox balance
towards reduction with enhanced metabolic activity and its recovery may correlate
with ROS generation. This phenomenon may mimic ROS generation following the
hypoxic status induced by transiently enhanced energy metabolism.
PMID- 28499833
TI - Mitochondrial dysfunction in cancer: Potential roles of ATF5 and the
mitochondrial UPR.
AB - Mitochondria form a cellular network of organelles, or cellular compartments,
that efficiently couple nutrients to energy production in the form of ATP. As
cancer cells rely heavily on glycolysis, historically mitochondria and the
cellular pathways in place to maintain mitochondrial activities were thought to
be more relevant to diseases observed in non-dividing cells such as muscles and
neurons. However, more recently it has become clear that cancers rely heavily on
mitochondrial activities including lipid, nucleotide and amino acid synthesis,
suppression of mitochondria-mediated apoptosis as well as oxidative
phosphorylation (OXPHOS) for growth and survival. Considering the variety of
conditions and stresses that cancer cell mitochondria may incur such as hypoxia,
reactive oxygen species and mitochondrial genome mutagenesis, we examine
potential roles for a mitochondrial-protective transcriptional response known as
the mitochondrial unfolded protein response (UPRmt) in cancer cell biology.
PMID- 28499834
TI - N-stearoyltyrosine protects primary cortical neurons against oxygen-glucose
deprivation-induced apoptosis through inhibiting anandamide inactivation system.
AB - N-stearoylthrosine (NST), a synthesized anandamide (AEA) analogue, plays a
neuroprotective role in neurodegenerative diseases and cerebrovascular diseases.
Several studies have demonstrated that the endocannabinoids systems (ECS) are
involved in the neuroprotective effects against cerebral ischemic injury. Oxygen
glucose deprivation (OGD)-induced neuronal injury elevated the levels of
endocannabinoids and activated ECS. This research was conducted to investigate
the neuroprotective effect of NST against OGD-induced neuronal injury in cultured
primary cortical neurons and the potential mechanism involved. Cortical neurons
were treated with NST at indicate concentrations for 30min prior to injury and
OGD injured neurons were incubated with normal conditions for 0-24h. The best
neuroprotective effect of NST against OGD-induced injury occurred at 10MUM. All
data indicated that the neuroprotective effect of NST against OGD-induced injury
resulted from blocking anandamide membrane transporter (AMT) (IC50=11.74nM) and
inhibiting fatty acid amide hydrolase activity (FAAH) (IC50=16.54nM). Our
findings demonstrated that NST has an important role in cerebral ischemic injury
pathological progression through activating cannabinoid receptors by inhibiting
AEA inactivation system. These data suggested a potential role for NST in the
therapeutic consideration of cerebral ischemic injury. However, inhibition of AEA
inactivation system may provide a neuroprotective effect during cerebral ischemic
injury.
PMID- 28499836
TI - Inhibitory Control for Emotional and Neutral Scenes in Competition: An Eye
Tracking Study in Bipolar Disorder.
AB - This study examined the inhibitory control of attention to social scenes in
manic, depressive, and euthymic episodes of bipolar disorder (BD). Two scenes
were simultaneously presented (happy/threatening/neutral [target] versus
control). Participants were asked either to look at the emotional pictures (i.e.,
attend-to-emotional block) or to avoid looking at the emotional pictures (i.e.,
attend-to-neutral block) while their eye movements were recorded. The initial
orienting (latency and percentage of first fixation) and subsequent attentional
engagement (gaze duration) were computed. Manic patients showed a higher
percentage of initial fixations on happy scenes than on the other scenes,
regardless of the instructions. However, in the attend-to-neutral block, their
gaze durations were longest for threatening scenes. Inhibitory control was not
modulated by the scene's emotional salience in the other groups. Thus, manic
patients had difficulties voluntarily ignoring emotional information - this was
characterized by a happy-related bias during initial orienting, but a threat
related bias during attentional engagement.
PMID- 28499837
TI - Information Processing of the Rorschach's Traumatic Content Index in Trauma
exposed Adults: An Event Related Potential (ERP) Study.
AB - PTSD elicits hypervigilance to trauma-related stimuli. Our novel research
examined event-related potentials from Blood, Anatomy, and Morbid content derived
from the Rorschach's traumatic content index (TCI). Participants included: 16
with PTSD, 24 trauma-exposed without PTSD (non-PTSD), and 16 non-traumatized
Controls. P3 oddball paradigms were used with TCI-derived Distractors and neutral
Targets/Standards. We predicted larger P3 amplitudes in the context of TCI
related Distractors among trauma-exposed participants. Significant interaction of
Group and Distractor type was found for P3 amplitude. PTSD and non-PTSD groups
exhibited larger P3 amplitudes from Blood and Anatomy Distractors, and attenuated
amplitudes from Morbid; the reverse pattern was found among Controls. A late
negative component was observed, denoting a significantly larger area under the
curve (AUC) among the PTSD group for Anatomy and Blood Distractors. Larger AUC's
were observed for Distractors among the PTSD group, and Targets among Controls.
The findings concur with the neurocircuitry model of PTSD and suggest impairment
in cerebral suppression of attention to stimuli that may have been perceptually
primed with trauma.
PMID- 28499838
TI - Brain responses to sound intensity changes dissociate depressed participants and
healthy controls.
AB - Depression is associated with bias in emotional information processing, but less
is known about the processing of neutral sensory stimuli. Of particular interest
is processing of sound intensity which is suggested to indicate central
serotonergic function. We tested weather event-related brain potentials (ERPs) to
occasional changes in sound intensity can dissociate first-episode depressed,
recurrent depressed and healthy control participants. The first-episode depressed
showed larger N1 amplitude to deviant sounds compared to recurrent depression
group and control participants. In addition, both depression groups, but not the
control group, showed larger N1 amplitude to deviant than standard sounds.
Whether these manifestations of sensory over-excitability in depression are
directly related to the serotonergic neurotransmission requires further research.
The method based on ERPs to sound intensity change is fast and low-cost way to
objectively measure brain activation and holds promise as a future diagnostic
tool.
PMID- 28499839
TI - Does emotion change auditory prediction and deviance detection?
AB - In the last decades, a growing number of studies provided compelling evidence
supporting the interplay of cognitive and affective processes. However, it
remains to be clarified whether and how an emotional context affects the
prediction and detection of change in unattended sensory events. In an event
related potential (ERP) study, we probed the modulatory role of pleasant,
unpleasant and neutral visual contexts on the brain response to automatic
detection of change in spectral (intensity) vs. temporal (duration) sound
features. Twenty participants performed a passive auditory oddball task.
Additionally, we tested the relationship between ERPs and self-reported mood.
Participants reported more negative mood after the negative block. The P2
amplitude elicited by standards was increased in a positive context. Mismatch
Negativity (MMN) amplitude was decreased in the negative relative to the neutral
and positive contexts, and was associated with self-reported mood. These findings
suggest that the detection of regularities in the auditory stream was facilitated
in a positive context, whereas a negative visual context interfered with
prediction error elicitation, through associated mood changes. Both ERP and
behavioral effects highlight the intricate links between emotion, perception and
cognitive processes.
PMID- 28499840
TI - Antimicrobial peptide KSL-W promotes gingival fibroblast healing properties in
vitro.
AB - We investigated the effect of synthetic antimicrobial decapeptide KSL-W
(KKVVFWVKFK) on normal human gingival fibroblast growth, migration, collagen gel
contraction, and alpha-smooth muscle actin protein expression. Results show that
in addition to promoting fibroblast adhesion by increasing F-actin production,
peptide KSL-W promoted cell growth by increasing the S and G2/M cell cycle
phases, and enhanced the secretion of metalloproteinase (MMP)-1 and MMP-2 by
upregulating MMP inhibitors, such as tissue inhibitors of metalloproteinase
(TIMP)-1 and TIMP-2 in fibroblasts. An in vitro wound healing assay confirmed
that peptide KSL-W promoted fibroblast migration and contraction of a collagen
gel matrix. We also demonstrated a high expression of alpha-smooth muscle actin
by gingival fibroblasts being exposed to KSL-W. This work shows that peptide KSL
W enhances gingival fibroblast growth, migration, and metalloproteinase
secretion, and the expression of alpha-smooth muscle actin, thus promoting wound
healing.
PMID- 28499841
TI - Effect of administration method, animal weight and age on the intranasal delivery
of drugs to the brain.
AB - BACKGROUND: The intranasal route of administration has proven to be an effective
method for bypassing the blood brain barrier and avoiding first pass hepatic
metabolism when targeting drugs to the brain. Most small molecules gain rapid
access to CNS parenchyma when administered intranasally. However, bioavailability
is affected by various factors ranging from the molecular weight of the drug to
the mode of intranasal delivery. COMPARISON WITH EXISTING METHODS: We examined
the effects of animal posture, intranasal application method and animal weight
and age on the delivery of radiolabeled pralidoxime (3H-2-PAM) to the brain of
rats. RESULTS: We found that using upright vs. supine posture did not
significantly affect 3H-2-PAM concentrations in different brain regions. Older
animals with higher weights required increased doses to achieve the same drug
concentration throughout the brain when compared to young animals with lower body
weights. The use of an intranasal aerosol propelled delivery device mainly
increased bioavailability in the olfactory bulbs, but did not reliably increase
delivery of the drug to various other brain regions, and in some regions of the
brain delivered less of the drug than simple pipette administration. CONCLUSION:
In view of the emerging interest in the use of intranasal delivery of drugs to
combat cognitive decline in old age, we tested effectiveness in very old rats and
found the method to be as effective in the older rats.
PMID- 28499842
TI - Establishing the ferret as a gyrencephalic animal model of traumatic brain
injury: Optimization of controlled cortical impact procedures.
AB - BACKGROUND: Although rodent TBI studies provide valuable information regarding
the effects of injury and recovery, an animal model with neuroanatomical
characteristics closer to humans may provide a more meaningful basis for clinical
translation. The ferret has a high white/gray matter ratio, gyrencephalic
neocortex, and ventral hippocampal location. Furthermore, ferrets are amenable to
behavioral training, have a body size compatible with pre-clinical MRI, and are
cost-effective. NEW METHODS: We optimized the surgical procedure for controlled
cortical impact (CCI) using 9 adult male ferrets. We used subject-specific
brain/skull morphometric data from anatomical MRIs to overcome across-subject
variability for lesion placement. We also reflected the temporalis muscle, closed
the craniotomy, and used antibiotics. We then gathered MRI, behavioral, and
immunohistochemical data from 6 additional animals using the optimized surgical
protocol: 1 control, 3 mild, and 1 severely injured animals (surviving one week)
and 1 moderately injured animal surviving sixteen weeks. RESULTS: The optimized
surgical protocol resulted in consistent injury placement. Astrocytic reactivity
increased with injury severity showing progressively greater numbers of
astrocytes within the white matter. The density and morphological changes of
microglia amplified with injury severity or time after injury. Motor and
cognitive impairments scaled with injury severity. COMPARISON WITH EXISTING
METHOD(S): The optimized surgical methods differ from those used in the rodent,
and are integral to success using a ferret model. CONCLUSIONS: We optimized
ferret CCI surgery for consistent injury placement. The ferret is an excellent
animal model to investigate pathophysiological and behavioral changes associated
with TBI.
PMID- 28499843
TI - Magnetic resonance imaging in dissociated strabismus complex demonstrates
generalized hypertrophy of rectus extraocular muscles.
AB - BACKGROUND: Dissociated strabismus complex (DSC) is an enigmatic form of
strabismus that includes dissociated vertical deviation (DVD) and dissociated
horizontal deviation (DHD). We employed magnetic resonance imaging (MRI) to
evaluate the extraocular muscles in DSC. METHODS: We studied 5 patients with DSC
and mean age of 25 years (range, 12-42 years), and 15 age-matched, orthotropic
control subjects. All patients had DVD; 4 also had DHD. We employed high
resolution, surface coil MRI with thin, 2 mm slices and central target fixation.
Volumes of the rectus and superior oblique muscles in the region 12 mm posterior
to 4 mm anterior to the globe-optic nerve junction were measured in quasi-coronal
planes in central gaze. RESULTS: Patients with DSC had no structural
abnormalities of rectus muscles or rectus pulleys or the superior oblique muscle
but exhibited modest, statistically significant increased volume of all rectus
muscles ranging from 20% for medial rectus to 9% for lateral rectus (P < 0.05).
CONCLUSIONS: DSC includes various combinations of sursumduction, excycloduction,
and abduction not conforming to Hering's law. We have found modest generalized
enlargement of all rectus muscles. DSC is associated with generalized rectus
extraocular muscle hypertrophy in the absence of other orbital abnormalities.
PMID- 28499844
TI - Inconclusive Exercise Stress Echocardiography in Patients With Chest Pain:
Prevalence and Clinical Determinants.
PMID- 28499845
TI - Exploring resistance pathways for first-generation NS3/4A protease inhibitors
boceprevir and telaprevir using Bayesian network learning.
AB - Resistance-associated variants (RAVs) have been shown to influence treatment
response to direct-acting antivirals (DAAs) and first generation NS3/4A protease
inhibitors (PIs) in particular. Interpretation of hepatitis C virus (HCV)
genotypic drug resistance remains a challenge, especially in patients who
previously failed DAA therapy and need to be retreated with a second DAA based
regimen. Bayesian network (BN) learning on HCV sequence data from patients
treated with DAAs could provide insight in resistance pathways against PIs for
HCV subtypes 1a and 1b, in a similar way as applied before for HIV. The publicly
available 'Rega-BN' tool chain was developed to study associative analyses for
various pathogens. Our first analysis, comparing sequences from PI-naive and PI
experienced patients, determined that NS3 substitutions R155K and V36M arise with
PI-exposure in HCV1a infected patients, and were defined as major and minor
resistance-associated variants respectively. NS3 variant 174H was newly
identified as potentially related to PI resistance. In a second analysis, NS3
sequences from PI-naive patients who cleared the virus during PI therapy and from
PI-naive patients who failed PI therapy were compared, showing that NS3 baseline
variant 67S predisposes to treatment-failure and variant 72I to treatment
success. This approach has the potential to better characterize the role of more
RAVs, if sufficient therapy annotated sequence data becomes available in curated
public databases. In addition, polymorphisms present in baseline sequences that
predispose patients to therapy failure can be identified using this approach.
PMID- 28499846
TI - Methodological quality is underrated in systematic reviews and meta-analyses in
health psychology.
AB - OBJECTIVES: In this paper, we compile and describe the main approaches proposed
in the literature to include methodological quality (MQ) or risk of bias (RoB)
into research synthesis. We also meta-review how the RoB of observational primary
studies is being assessed and to what extent the results are incorporated in the
conclusions of research synthesis. STUDY DESIGN AND SETTING: Electronic databases
were searched for systematic reviews or meta-analyses related to health and
clinical psychology. A random sample of 90 reviews published between January 2010
and May 2016 was examined. RESULTS: A total of 46 reviews (51%) performed a
formal assessment of the RoB of primary studies. Only 17 reviews (19%) linked the
outcomes of quality assessment with the results of the review. CONCLUSION:
According to the previous literature, our results corroborate the lack of
guidance to incorporate the RoB assessment in the results of systematic reviews
and meta-analyses. Our recommendation is to appraise MQ according to domains of
RoB to rate the degree of credibility of the results of a research synthesis, as
well as subgroup analysis or meta-regression as analytical methods to incorporate
the quality assessment.
PMID- 28499847
TI - GRADE equity guidelines 2: considering health equity in GRADE guideline
development: equity extension of the guideline development checklist.
AB - OBJECTIVE: To provide guidance for guideline developers on how to consider health
equity at key stages of the guideline development process. STUDY DESIGN AND
SETTING: Literature review followed by group discussions and consensus building.
RESULTS: The key stages at which guideline developers could consider equity
include setting priorities, guideline group membership, identifying the target
audience(s), generating the guideline questions, considering the importance of
outcomes and interventions, deciding what evidence to include and searching for
evidence, summarizing the evidence and considering additional information,
wording of recommendations, and evaluation and use. We provide examples of how
guidelines have actually considered equity at each of these stages. CONCLUSION:
Guideline projects should consider the aforementioned suggestions for
recommendations that are equity sensitive.
PMID- 28499848
TI - Understanding obesity in the context of an Indigenous population-A qualitative
study.
AB - BACKGROUND: Obesity is a progressive global phenomenon that is disparately
prevalent amongst Indigenous populations. While there is a growing body of
literature investigating the extrinsic contributors to obesity, there is a lack
of evidence to elucidate intrinsic drivers in the context of an Indigenous
population. METHODS: Qualitative research theory, inclusive of Indigenous
knowledge systems, was applied to the narratives of 15 Indigenous (Maori) people
aged between 18 and 65 to contextualise their understandings of obesity. RESULTS:
Thematic analysis of the interview data revealed four intrinsic determinants for
obesity expression that specifically relate to Indigenous peoples: (1)
relationships and social connectedness; (2) holistic health including spiritual
beliefs and cultural practices (Indigenous worldview); (3) historical trauma and
the impacts of colonisation; and (4) the biomedical model of caloric restriction,
diet and exercise were culturally insensitive, non-relatable, and were not
significant drivers for engagement in healthier lifestyles. DISCUSSION AND
CONCLUSIONS: Similar to non-Indigenous populations, Indigenous understandings of
obesity are multi-factorial. What was unique about the findings of this study
were insights into the importance of relational aspects and connectedness to each
other and the environment, as determinants for obesity expression. This suggests
that the current individualistic approaches of western medicine to obesity
management are not culturally aligned with Indigenous peoples ways of being.
Adopting an ontology of connectedness may represent a more culturally centred
approach, and help build epistemological resilience to mitigate rising obesity
incidence in Indigenous populations.
PMID- 28499850
TI - Skeletal muscle protease activities in the early growth and development of wild
Atlantic salmon (Salmo salar L.).
AB - Growth-related dynamics of intracellular protease activities in four year classes
of the Atlantic salmon (Salmo salar L. 1758) parr and smolts inhabiting salmon
rivers of northwestern Russia (the White Sea basin) were studied. Cathepsin B,
cathepsin D, proteasome, and calpain activities in the skeletal muscles of salmon
were assessed to investigate their relative contribution to the total protein
degradation as well as to young fish growth process. It was confirmed that
calpain activity dominates in salmon muscles while proteasome plays a minor role,
in contrast to terrestrial vertebrates. Calpain and proteasome activities were
maximal at the early post-larval stage (in parrs 0+) and declined with age (parrs
1+ through 2+) dropping to the lowest level in salmon smolts. Annual growth
increments and proteolytic activities of calpains and proteasome in the muscles
of salmon juveniles changed with age in an orchestrated manner, while lysosomal
cathepsin activities increased with age. Comparing protease activities and growth
increments in salmon parr and smolts we suggested that the partial suppression of
the protein degradation could be a mechanism stimulating efficient growth in
smoltifying salmon. Growth and smoltification-related dynamics of protease
activities was quite similar in salmon populations from studied spawning rivers,
such as Varzuga and Indera; however, some habitat-related differences were
observed. Growth increments and protease activities varied in salmon parr 0+ (but
not on later ages) inhabiting either main rivers or small tributaries apparently
due to habitat difference on the resources for fish growth.
PMID- 28499849
TI - A geometrically adjustable receive array for imaging marmoset cohorts.
AB - The common marmoset (Callithrix jacchus) is an increasingly popular animal model
for translational neuroscience studies, during which anatomical and functional
MRI can be useful investigative tools. To attain the requisite SNR for high
resolution acquisitions, the radiofrequency coil must be optimized for the
marmoset; however, relatively few custom coils have been developed that maximize
SNR and are compatible with accelerated acquisitions. For the study of large
populations of animals, the heterogeneity in animal size reduces the
effectiveness of a "one size fits all" approach to coil sizing and makes coils
tailored to individual animals cost and time prohibitive. The approach taken in
this study was to create an 8-channel phased-array receive coil that was
adjustable to the width of the marmoset head, thereby negating the need for
tailored coils while still maintaining high SNR. Two marmosets of different size
were imaged on a 9.4-T small-animal scanner. Consistent SNR was achieved in the
periphery of the brain between head sizes. When compared to a 15-channel, "one
size fits all" receive coil, the adjustable coil achieved 57% higher SNR in the
superior frontal and parietal cortices and 29% higher SNR in the centre of the
brain. The mean geometry factor of the adjustable coil was less than 1.2 for a 2
fold reduction factor in the left-right and anterior-posterior directions.
Geometry factors were compared to the 15-channel coil to guide future designs.
The adjustable coil was shown to be a practical means for anatomical and echo
planar imaging of marmoset cohorts.
PMID- 28499852
TI - Withdrawal of antiepileptic drugs: an individualised approach.
PMID- 28499851
TI - Effects of nutritional history on stress response in gibel carp (Carassius
auratus gibelio) and largemouth bass (Micropterus salmoides).
AB - The stress response of omnivorous gibel carp (Carassius auratus gibelio) and
carnivorous largemouth bass (Micropterus salmoides) with different nutritional
history were evaluated. A 2*2 layout, including two fish species (gibel carp or
largemouth bass) and two nutritional history (fasted or fed to satiation for four
weeks), was used. After feeding or fasting, the fishes were subjected to an acute
handling. Fasting resulted in decrease of plasma glucose level and liver glycogen
content of gibel carp and largemouth bass. After handling stress, plasma levels
of cortisol, glucose and lactate of gibel carp and largemouth bass increased,
regardless the fasted fish or fed fish. During the period from 0h to 24h post
stress, the fasted gibel carp exhibited lower plasma cortisol and glucose levels,
brain and liver glycogen contents, and liver phosphoenolpyruvate carboxykinase
(PEPCK) activity compared with the fed counterpart. The plasma glucose level,
brain glucose level, brain and liver glycogen contents were lower, while the
liver PEPCK and hexokinase (HK) activities were higher, in the faster largemouth
bass than the fed counterpart. This study indicates that nutritional history can
influence stress response of gibel carp and largemouth bass, and the stress
response is less severe in the fasted fish relative to the fed counterpart. This
study also reveals that gibel carp and largemouth bass may have different
strategies in response to fasting and acute handling stress.
PMID- 28499853
TI - Epilepsy and two evolving societies.
PMID- 28499854
TI - Curcumin loading potentiates the chemotherapeutic efficacy of selenium
nanoparticles in HCT116 cells and Ehrlich's ascites carcinoma bearing mice.
AB - The anticancer properties of selenium (Se) and curcumin nanoparticles in solo
formulations as well as in combination with other therapeutic agents have been
proved time and again. Exploiting this facet of the two, we clubbed their
tumoricidal characteristics and designed curcumin loaded Se nanoparticles (Se
CurNPs) to achieve an enhanced therapeutic effect. We evaluated their therapeutic
effects on different cancer cell lines and Ehrlich's ascites carcinoma mouse
model. In vitro results showed that Se-CurNPs were most effective on colorectal
carcinoma cells (HCT116) compared to the other cancer cell lines used and
possessed pleiotropic anticancer effects. The therapeutic effect on HCT116 was
primarily attributed to an elevated level of autophagy and apoptosis as evident
from significant up-regulation of autophagy associated (LC3B-II) and pro
apoptotic (Bax) proteins, down-regulation of anti-apoptotic (Bcl-2) protein and
Cytochrome c (cyt c) release from mitochondria along with reduced NFkappaB
signaling and EMT based machineries marked by downregulation of inflammation
(NFkappaB, phospho-NFkappaB) and epithelial-mesenchymal transition (CD44, N
cadherin) associated proteins. In vivo studies on Ehrlich's ascites carcinoma
(EAC) mice model indicated that Se-CurNPs significantly reduced the tumor load
and enhanced the mean survival time (days) of tumor-bearing EAC mice.
PMID- 28499855
TI - Electrolyte type and nozzle composition affect the process of vibrating-membrane
nebulization.
AB - The size of airborne particles determines their deposition pattern within the
lungs and therefore, the efficacy of inhalation therapy. The present study
analyzed factors affecting liquid atomization performed by vibrating-membrane
technology. First, the process of vibrating-membrane nebulization (eFlow(r)rapid
and Aeroneb(r) Pro) was challenged with numerous inorganic salts and active
pharmaceutical ingredients. All investigated samples caused a sigmoidal decrease
in aerosol droplet size upon an increase in concentration. Calculated dose-effect
curve characteristics (i.e., half maximal effective sample concentration inducing
a halfway drop of the droplet size) indicated distinct molar "potency" amongst
the utilized samples with respect to generation of "adequate" inhalation
aerosols. Second, the employed solvent (aqueous vs. organic) was shown to amplify
the electrolyte effect on vibrating-membrane technology (i.e., dose-effect curve
characteristics and overall aerosol droplet size). Third, besides the sample and
solvent type, the nozzle composition (diverse metal and polymer coatings) induced
a strong impact on the current mode of nebulization. Here, coating materials were
identified, which necessitated higher and lower electrolyte concentrations in
order to decrease the aerosol droplet size in comparable manner to plain
nebulizer membranes. Thus, depending on the employed sample type and
concentration, solvent and nozzle composition, a delivery of "inadequate" or
"adequate" aerosols for inhalation purpose was observed. Overall, the current
observations could be used to compile suggestions for the rational design of
aerosol formulations and nebulizer devices meeting the specific requirements for
successful inhalation therapy.
PMID- 28499857
TI - Preface to the special issue "Impact of omics on comparative immunology".
PMID- 28499856
TI - Measuring Soldier Performance During the Patrol-Exertion Multitask: Preliminary
Validation of a Postconcussive Functional Return-to-Duty Metric.
AB - OBJECTIVE: To assess the discriminant validity of the Patrol-Exertion Multitask
(PEMT), a novel, multidomain, functional return-to-duty clinical assessment for
active duty military personnel. DESIGN: Measurement development study. SETTING:
Nonclinical indoor testing facility. PARTICIPANTS: Participants (N=84) were
healthy control (HC) service members (SMs; n=51) and military personnel (n=33)
with persistent postconcussive symptoms receiving rehabilitation (mild traumatic
brain injury [mTBI]). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Known
groups discriminant validity was evaluated by comparing performance on the PEMT
in 2 groups of active duty SMs: HCs and personnel with mTBI residual symptoms.
Participant PEMT performance was based on responses in 4 subtasks during a 12
minute patrolling scenario: (1) accuracy in identifying virtual improvised
explosive device (IED) markers and responses to scenario-derived questions from a
computer-simulated foot patrol; (2) auditory reaction time responses; (3) rating
of perceived exertion during stepping; and (4) self-reported visual clarity (ie,
gaze stability) during vertical head-in-space translation while stepping.
RESULTS: Significant between-group differences for the PEMT were observed in 2 of
4 performance domains. Postpatrol IED identification task/question responses
(P=.179) and rating of perceived exertion (P=.133) did not discriminate between
groups. Participant self-report of visual clarity during stepping revealed
significant (P<.001) between-group differences. SM reaction time responses to
scenario-based auditory cues were significantly delayed in the mTBI group in both
the early (P=.013) and late (P=.002) stages of the PEMT. CONCLUSIONS: Findings
from this study support the use of a naturalistic, multidomain, complex clinical
assessment to discriminate between healthy SMs and personnel with mTBI residual
symptoms. Based on this preliminary study, additional research to further refine
the PEMT and extend its application to return-to-work outcomes in military and
civilian environments is warranted.
PMID- 28499859
TI - Reply to Letter to the Editor by Griffiths et al. commenting on Evans & Allen.
PMID- 28499858
TI - Enhanced behavioral immune defenses in a C. elegans C-type lectin-like domain
gene mutant.
AB - C-type lectin-like domain (CTLD) proteins occupy crucial functions in the immune
system of vertebrates, but their role in invertebrate immunity is much less
understood. The nematode Caenorhabditis elegans possesses a highly diverse CTLD
protein encoding (clec) gene repertoire. A role of C. elegans clec genes in
pathogen defense is always assumed, yet experimental evidence for clec immune
function is rare. To systematically test the potential function of clec genes in
the C. elegans defense against pathogens, we screened 39 clec mutants for
survival on the Gram-positive pathogen Bacillus thuringiensis (BT18247) and 37
clec mutants on the Gram-negative pathogen Pseudomonas aeruginosa (PA14). We
found that clec mutants can exhibit either decreased or, unexpectedly, increased
resistance to infection. Since we observed high escape behavior for some of the
clec mutants on BT18247 during the initial screen, we then asked if increased
pathogen avoidance behavior underlies the increased resistance of some clec
mutants. We thus tested lawn leaving behavior of the resistant clec-29(ok3181),
clec-34(ok2120), clec-151(ok2264), and C54G4.4(ok2110) mutant on BT18247. We
found that C54G4.4(ok2110) mutant animals exhibit a particularly strong lawn
leaving behavior, in addition to prolonged feeding cessation when exposed to
BT18247. Together, our results indicate that clec genes mediate both resistance
and susceptibility to infection. Further, behavioral analyses of the
C54G4.4(ok2110) mutant implicate C54G4.4 in the regulation of pathogen avoidance
behavior towards BT18247. We conclude that C. elegans clec genes may act both as
positive and negative regulators of physiological as well as behavioral immune
defense responses.
PMID- 28499860
TI - Circulating Tumor DNA Identifies EGFR Coamplification as a Mechanism of
Resistance to Crizotinib in a Patient with Advanced MET-Amplified Lung
Adenocarcinoma.
PMID- 28499861
TI - The Cost-Effectiveness of High-Risk Lung Cancer Screening and Drivers of Program
Efficiency.
AB - INTRODUCTION: Lung cancer risk prediction models have the potential to make
programs more affordable; however, the economic evidence is limited. METHODS:
Participants in the National Lung Cancer Screening Trial (NLST) were
retrospectively identified with the risk prediction tool developed from the
Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. The high-risk
subgroup was assessed for lung cancer incidence and demographic characteristics
compared with those in the low-risk subgroup and the Pan-Canadian Early Detection
of Lung Cancer Study (PanCan), which is an observational study that was high-risk
selected in Canada. A comparison of high-risk screening versus standard care was
made with a decision-analytic model using data from the NLST with Canadian cost
data from screening and treatment in the PanCan study. Probabilistic and
deterministic sensitivity analyses were undertaken to assess uncertainty and
identify drivers of program efficiency. RESULTS: Use of the risk prediction tool
developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial
with a threshold set at 2% over 6 years would have reduced the number of
individuals who needed to be screened in the NLST by 81%. High-risk screening
participants in the NLST had more adverse demographic characteristics than their
counterparts in the PanCan study. High-risk screening would cost $20,724 (in 2015
Canadian dollars) per quality-adjusted life-year gained and would be considered
cost-effective at a willingness-to-pay threshold of $100,000 in Canadian dollars
per quality-adjusted life-year gained with a probability of 0.62. Cost
effectiveness was driven primarily by non-lung cancer outcomes. Higher
noncurative drug costs or current costs for immunotherapy and targeted therapies
in the United States would render lung cancer screening a cost-saving
intervention. CONCLUSIONS: Non-lung cancer outcomes drive screening efficiency in
diverse, tobacco-exposed populations. Use of risk selection can reduce the budget
impact, and screening may even offer cost savings if noncurative treatment costs
continue to rise.
PMID- 28499862
TI - Successful Revascularization of Aortic Arch in a 39-Year-Old Blunt Trauma Patient
with Acute Diffuse Axonal Injury without the Use of Systemic Anticoagulation.
AB - Blunt traumatic aortic injury is the second leading cause of death in trauma
patients aged 4-34 years. Of the patients who are able to receive treatment,
mortality rates as high as 40% have been reported. Endovascular repair options
have allowed for more expeditious repairs with reduced iatrogenic trauma;
however, when the injury involves the ascending aorta or arch, current endografts
lack fenestrations needed for cerebral blood flow. Traditionally, on pump,
cardiopulmonary bypass with systemic anticoagulation has been used to repair
these injuries. In this paper, we describe a unique case of repairing a large
traumatic aortic arch pseudoaneurysm in the setting of which systemic
anticoagulation is contraindicated. The patient is a 39-year-old otherwise
healthy Hispanic male who presented to Ryder Trauma Center in Miami, Florida,
following a motor vehicle collision and found to have multiple intracranial
hemorrhages and a large aortic pseudoaneurysm of the distal ascending aorta. In
lieu of standard cardiopulmonary bypass, a hybrid approach was utilized. Cranial
blood flow was maintained using a temporary extra-anatomical left femoral to
bilateral carotid bypass during endovascular coverage of the aortic arch. Aortic
arch revascularization was then achieved by means of in situ laser fenestration
of the innominate artery followed by a right-to-left carotid-carotid-subclavian
bypass. This case demonstrates the viability of a hybrid vascular repair of a
complex aortic disruption without the use of systemic anticoagulation in the
setting of contraindicated or unknown risk of systemic anticoagulation. Further
research is warranted on whether emergent traumatic cases with contraindications
to anticoagulation can be performed in a similar fashion to safely reduce the
morbidity and mortality associated with aortic disruptions.
PMID- 28499863
TI - Innovative Procedure for Inferior Mesenteric Artery Embolization Using the
Amplatzer Vascular Plug 4 during Endovascular Aneurysm Repair.
AB - PURPOSE: The aim of this study is to present an easy and quick technique for
embolization of the inferior mesenteric artery (IMA) during endovascular aneurysm
repair (EVAR). TECHNIQUE: We performed IMA embolization using a conventional EVAR
device alone with the femoral artery approach during EVAR, which has not been
reported previously. First, a 16F or 18F DrySeal Sheath is inserted from the
femoral artery into the site around the IMA. Second, cannulation is performed in
the IMA with an angiography catheter having a 0.038-inch inner lumen that is used
for gate cannulation during EVAR. Third, IMA embolization is performed using the
Amplatzer Vascular Plug 4 (AVP4). The use of the DrySeal Sheath facilitates
cannulation of the IMA, and its combination with a stent-graft balloon allows the
AVP4 to be placed at the root of the IMA without deviation of the catheter. The
success rate of the procedure was 90.9% (30/33 cases). The median procedure time
was 11.6 min. No complications due to IMA embolization were noted. CONCLUSION:
This procedure enables safe and quick placement of the AVP4 in the IMA using the
catheter insertion approach from the femoral artery, which has been
conventionally regarded as difficult.
PMID- 28499864
TI - Role of hepatitis B core protein in HBV transcription and recruitment of histone
acetyltransferases to cccDNA minichromosome.
AB - The hepatitis B core protein (HBc) has been suggested to interact with covalently
closed circular DNA (cccDNA) and regulate hepatitis B virus (HBV) transcription.
However, direct evidence is lacking. We aimed to identify the specific HBc
region(s) responsible for transcription regulation and its interaction with
cccDNA. Seventeen mutants with mutations at the four arginine-rich clusters of
the HBc carboxyl-terminal domain (CTD) were created. The effect of HBc mutations
on the levels of HBV DNA, RNA, and hepatitis B surface antigen (HBsAg) were
measured. The association of cccDNA with mutant HBc and histone
acetyltransferases (HATs) was assessed by chromatin immunoprecipitation (ChIP).
Compared with wild-type HBc, HBc mutants with mutations in clusters III and IV
resulted in a significant reduction in HBV RNA levels (all P < 0.05). HBc
arginine clusters III and IV mutants also had a significantly lower levels of
intracellular HBV DNA (<5% of wild-type; P < 0.001) and HBsAg (<10% of wild-type;
P < 0.0001). cccDNA-ChIP assay demonstrated that HBc clusters III and IV mutants
had a smaller degree of association with cccDNA (P < 0.001). In the HBc mutants,
the association between HATs with cccDNA were reduced. In conclusion, HBc-CTD
arginine residues at clusters III and IV play an important role in the regulation
of HBV transcription as well as subsequent replication steps, likely through the
reduced interaction of HBc with cccDNA and reduced acetylation of cccDNA-bound
histones. These findings may provide clues to the identification of novel
therapeutic targets against HBV.
PMID- 28499865
TI - Implication of altered autonomic control for orthostatic tolerance in SCI.
AB - Neural output from the sympathetic and parasympathetic branches of the autonomic
nervous system (ANS) are integrated to appropriately control cardiovascular
responses during routine activities of daily living including orthostatic
positioning. Sympathetic control of the upper extremity vasculature and the heart
arises from the thoracic cord between T1 and T5, whereas splanchnic bed and lower
extremity vasculature receive sympathetic neural input from the lower cord
between segments T5 and L2. Although the vasculature is not directly innervated
by the parasympathetic nervous system, the SA node is innervated by post
ganglionic vagal nerve fibers via cranial nerve X. Segmental differences in
sympathetic cardiovascular innervation highlight the effect of lesion level on
orthostatic cardiovascular control following spinal cord injury (SCI). Due to
impaired sympathetic cardiovascular control, many individuals with SCI,
particularly those with lesions above T6, are prone to orthostatic hypotension
(OH) and orthostatic intolerance (OI). Symptomatic OH, which may result in OI, is
a consequence of episodic reductions in cerebral perfusion pressure and the
symptoms may include: dizziness, lightheadedness, nausea, blurred vision, ringing
in the ears, headache and syncope. However, many, if not most, individuals with
SCI who experience persistent and episodic hypotension and OH do not report
symptoms of cerebral hypoperfusion and therefore do not raise clinical concern.
This review will discuss the mechanism underlying OH and OI following SCI, and
will review our knowledge to date regarding the prevalence, consequences and
possible treatment options for these conditions in the SCI population.
PMID- 28499866
TI - Identification and characterization of novel lncRNAs in Arabidopsis thaliana.
AB - Long noncoding RNAs (lncRNAs) are important regulators of various biological
processes, but few studies have identified lncRNAs in plants; genome-wide
discovery of novel lncRNAs is thus required. We used deep strand-specific
sequencing (ssRNA-seq) to obtain approximately 62 million reads from all
developmental stages of Arabidopsis thaliana and identified 156 novel lncRNAs
that we classified according to their localization. These novel identified
lncRNAs showed low expression levels and sequence conservation. Bioinformatic
analysis predicted potential target genes or cis-regulated genes of 91 antisense
and 32 intergenic lncRNAs. Functional annotation of these potential targets and
sequence motif analysis indicated that the lncRNAs participate in various
biological processes underlying Arabidopsis growth and development. Seventeen of
the lncRNAs were predicted targets of 22 miRNAs, and a network of interactions
between ncRNAs and mRNAs was constructed. In addition, nine lncRNAs functioned as
miRNA precursors. Finally, qRT-PCR revealed that novel lncRNAs have stage- and
tissue-specific expression patterns in A. thaliana. Our study provides insight
into the potential functions and regulatory interactions of novel Arabidopsis
lncRNAs, and enhances our understanding of plant lncRNAs, which will facilitate
functional research.
PMID- 28499867
TI - Glycine-nitronyl nitroxide conjugate protects human umbilical vein endothelial
cells against hypoxia/reoxygenation injury via multiple mechanisms and
ameliorates hind limb ischemia/reperfusion injury in rats.
AB - Oxidative stress and inflammation play important roles in the pathogenesis of
ischemia/reperfusion (I/R)-injury. The administration of antioxidants and anti
inflammatory agents has been applied to prevent I/R-injury for several decades.
Of the numerous compounds administrated therapeutically in anti-oxidative stress,
nitronyl nitroxide has gained increasing attention due to its continuous ability
to scavenge active oxygen radicals. However, its effect is not ideal in clinical
therapy. In previous study, we linked the anti-inflammatory amino acid glycine to
nitronyl nitroxide and developed a novel glycine-nitronyl nitroxide (GNN)
conjugate, which showed a synergetic protection against renal
ischemia/reperfusion injury. However, the underlying mechanism remains unclear.
In this study, a hypoxia/reoxygenation (H/R) injury model was established in
human umbilical vein endothelial cells (HUVECs) and we found that the GNN
conjugate significantly elevated the cell viability via reducing the apoptosis
rate in H/R-treated HUVECs. Meanwhile, GNN conjugate attenuated H/R induced
mitochondrial fragmentation, mitochondrial membrane potential reduction,
Cytochrome c release and autophagy. To determine the extensive applicability of
GNN conjugate in different I/R models and its effect in remote organs, an in vivo
hind limb I/R model was established. As expected, GNN conjugate ameliorated
damages of muscle and remote organs. These results demonstrate that GNN conjugate
may be an effective agent against ischemia/reperfusion injury in clinical
therapy.
PMID- 28499868
TI - Exposure to particulate matter induces cardiomyocytes apoptosis after myocardial
infarction through NFkappaB activation.
AB - Clinical evidence has indicated an increased myocardial infarction (MI) morbidity
and mortality after exposure to air pollution (particulate matter<2.5 MUm,
PM2.5). However, the mechanisms by which PM2.5 aggravates MI remain unknown.
Present study was to explore the adverse effect of PM2.5 on myocardium after MI
and the potential mechanisms. Male mice with MI surgery were treated with PM2.5
by intranasal instillation. Neonatal mice ventricular myocytes (NMVMs) subjected
to hypoxia were also incubated with PM2.5 to determine the role of PM2.5 in
vitro. Exposure to PM2.5 significantly impaired the cardiac function and
increased the infarct size in MI mice. TUNEL assay, flow cytometry and western
blotting of Caspase 3, Bax and BCl-2 indicated that PM2.5 exposure could cause
cellular apoptosis in vivo and in vitro. Besides, PM2.5 activated NFkappaB
pathway and increased gene expression of IL-1beta and IL-6 in NMVMs with hypoxia,
which could be effectively reversed by SN-50-induced blockade of NFkappaB
translocation to the nucleus. In summary, air pollution induces myocardium
apoptosis and then impairs cardiac function and aggravates MI via NFkappaB
activation.
PMID- 28499869
TI - RNF8 negatively regulates NF-kappaB signaling by targeting IkappaB kinase:
implications for the regulation of inflammation signaling.
AB - Persistent or excess activation of NF-kappaB leads to cancer, autoimmune and
inflammatory diseases. Therefore, activated NF-kappaB needs to be terminated
after induction, which highlights the physiological significance of NF-kappaB
negative regulators. However, the molecular mechanisms that negatively regulate
NF-kappaB are not well understood. Here, we report that Ring Finger Protein 8
(RNF8), an E3 ubiquitin ligase, inhibits TNFalpha-mediated NF-kappaB activation
by targeting IkappaB kinase (IKK). Upon TNFalpha stimulation, RNF8 binds to the
catalytic subunits of IKK complex, resulting in inhibition of IKKalpha/beta
phosphorylation and subsequent NF-kappaB activation. RNF8 targets the IKK complex
in a manner independent of its RING domain. We further provide evidence that the
silencing of RNF8 results in enhanced TNFalpha-induced IKK activation, and an
increase expression of NF-kappaB-induced inflammatory cytokine IL-8. Our study
identifies a previously unrecognized role for RNF8 in the negative regulation of
NF-kappaB activation by targeting and deactivating the IKK complex.
PMID- 28499870
TI - Fibronectin on extracellular vesicles from microvascular endothelial cells is
involved in the vesicle uptake into oligodendrocyte precursor cells.
AB - We previously reported transplantation of brain microvascular endothelial cells
(MVECs) into cerebral white matter infarction model improved the animal's
behavioral outcome by increasing the number of oligodendrocyte precursor cells
(OPCs). We also revealed extracellular vesicles (EVs) derived from MVECs promoted
survival and proliferation of OPCs in vitro. In this study, we investigated the
mechanism how EVs derived from MVECs contribute to OPC survival and
proliferation. Protein mass spectrometry and enzyme-linked immunosorbent assay
revealed fibronectin was abundant on the surface of EVs from MVECs. As
fibronectin has been reported to promote OPC survival and proliferation via
integrin signaling pathway, we blocked the binding between fibronectin and
integrins using RGD sequence mimics. Blocking the binding, however, did not
attenuate the survival and proliferation promoting effect of EVs on OPCs. Flow
cytometric and imaging analyses revealed fibronectin on EVs mediates their
internalization into OPCs by its binding to heparan sulfate proteoglycan on OPCs.
OPC survival and proliferation promoted by EVs were attenuated by blocking the
internalization of EVs into OPCs. These lines of evidence suggest that
fibronectin on EVs mediates their internalization into OPCs, and the cargo of EVs
promotes survival and proliferation of OPCs, independent of integrin signaling
pathway.
PMID- 28499871
TI - Synthesis of a new deoxyglucose derivative modified near-infrared fluorescent
probe for tumor diagnosis.
AB - Malignant neoplasms exhibit an elevated rate of glycolysis and a high demand for
glucose over normal cells. This characteristic can be exploited for in vivo
imaging and tumor targeting examined. In this manuscript, we describe the
synthesis of near-infrared (NIR) fluorochrome IR-822-labeled 2-amino-2-deoxy-d
glucose (DG) for optical imaging of tumors in mice. NIR fluorescent dye IR-820
was subsequently conjugated with 3-Mercaptopropionic acid and 2-amino-2-deoxy-d
glucose to form IR-822-DG. The cell experiments and acute toxicity studies
demonstrated the low toxicity of IR-822-DG to normal cells/tissues. The dynamic
behavior and targeting ability of IR-822-DG in normal mice was investigated with
a NIR fluorescence imaging system. The in vitro and in vivo tumor targeting
capabilities of IR-822-DG were evaluated in tumor cells and tumor bearing mice,
respectively. Results demonstrated that IR-822-DG actively and efficiently
accumulated at the site of the tumor. The probe also exhibited good
photostability and excellent cell membrane permeability. The study indicates the
broad applicability of IR-822-DG for tumors diagnosis, especially in the glucose
related pathologies.
PMID- 28499872
TI - Interaction of Flavivirus with their mosquito vectors and their impact on the
human health in the Americas.
AB - Some of the major arboviruses with public health importance, such as dengue,
yellow fever, Zika and West Nile virus are mosquito-borne or mosquito-transmitted
Flavivirus. Their principal vectors are from the family Culicidae, Aedes aegypti
and Aedes albopictus being responsible of the urban cycles of dengue, Zika and
yellow fever virus. These vectors are highly competent for transmission of many
arboviruses. The genetic variability of the vectors, the environment and the
viral diversity modulate the vector competence, in this context, it is important
to determine which vector species is responsible of an outbreak in areas where
many vectors coexist. As some vectors can transmit several flaviviruses and some
flaviviruses can be transmitted by different species of vectors, through this
review we expose importance of yellow fever, dengue and Zika virus in the world
and the Americas, as well as the updated knowledge about these flaviviruses in
their interaction with their mosquito vectors, guiding us on what is probably the
beginning of a new stage in which the simultaneity of outbreaks will occur more
frequently.
PMID- 28499873
TI - Inhibition of bioluminescence in the living gills of the luminous fungus Mycena
chlorophos by trans-4-aminocinnamic acid.
AB - The living gills of the fungus Mycena chlorophos spontaneously emit green light.
It was previously reported that trans-4-hydroxycinnamic acid and trans-3,4
dihydroxycinnnamic acid are essential for the bright light production in the
living gills. However, the chemical mechanisms underlying their bioluminescence
are unknown. In the present study, trans-4-aminocinnamic acid was found to
inhibit light production in the living gills. The concentrations of trans-4
aminocinnamic acid that inhibited the bioluminescence intensity by 50% of initial
values for immature and mature gills were 0.07 MUM and 4 MUM, respectively.
Approximately 20% of the bioluminescence intensity of the immature and mature
gills was not inhibited by a further increase in the concentration of trans-4
aminocinnamic acid. Moreover, the bioluminescence that was activated by trans-4
hydroxycinnamic acid or trans-3,4-dihydroxycinnamic acid (0.01 mM) was completely
inhibited by trans-4-aminocinnamic acid. Therefore, trans-4-hydroxycinnamic acid
and trans-3,4-dihydroxycinnamic acid functioned for the bioluminescence that was
inhibited by trans-4-aminocinnamic acid. trans-4-Aminocinnamic acid strongly
bound to the bioluminescence system(s) and withstood rinsing of the gills with 10
mM phosphate buffer (pH = 7), and high concentrations of trans-4-hydroxycinnamic
acid (1 mM) and trans-3,4-dihydroxycinnamic acid (0.1 mM) functioned to displace
trans-4-aminocinnamic acid from the bioluminescence system(s) and reactivate
bioluminescence. Benzenamine, trans-cinnamic acid, trans-2-aminocinnamic acid,
and trans-3-aminocinnamic acid did not inhibit bioluminescence. Therefore, the
structure-specific inhibition by trans-4-aminocinnamic acid suggested that the 4
hydroxy group in trans-4-hydroxycinnamic acid and trans-3,4-dihydroxycinnamic
acid molecules plays a functional role in the bioluminescence reaction.
PMID- 28499874
TI - Pyrrole-indolinone SU11652 targets the nucleoside diphosphate kinase from
Leishmania parasites.
AB - Nucleoside diphosphate kinases (NDKs) are key enzymes in the purine-salvage
pathway of trypanosomatids and have been associated with the maintenance of host
cell integrity for the benefit of the parasite, being potential targets for
rational drug discovery and design. The NDK from Leishmania major (LmNDK) and
mutants were expressed and purified to homogeneity. Thermal shift assays were
employed to identify potential inhibitors for LmNDK. Calorimetric experiments,
site-directed mutagenesis and molecular docking analysis were performed to
validate the interaction and to evaluate the structural basis of ligand
recognition. Furthermore, the anti-leishmanial activity of the newly identified
and validated compound was tested in vitro against different Leishmania species.
The molecule SU11652, a Sunitinib analog, was identified as a potential inhibitor
for LmNDK and structural studies indicated that this molecule binds to the active
site of LmNDK in a similar conformation to nucleotides, mimicking natural
substrates. Isothermal titration calorimetry experiments combined with site
directed mutagenesis revealed that the residues H50 and H117, considered
essential for catalysis, play an important role in ligand binding. In vitro cell
studies showed that SU11652 had similar efficacy to Amphotericin b against some
Leishmania species. Together, our results indicate the pyrrole-indolinone SU11652
as a promising scaffold for the rational design of new drugs targeting the enzyme
NDK from Leishmania parasites.
PMID- 28499875
TI - Natural zwitterionic l-Carnitine as efficient cryoprotectant for solvent-free
cell cryopreservation.
AB - Organic solvents, such as dimethyl sulfoxide (DMSO) and glycerol, have been
commonly used as cryoprotectants (CPAs) in cell cryopreservation. However, their
cytotoxicity and need of complex freezing protocols have impeded their
applications especially in clinical cell therapy and regenerative medicine.
Trehalose has been explored as a natural CPA to cryopreserve cells, but its poor
cell permeability frequently results in low cryopreservation efficacy. In this
work, we presented that a natural zwitterionic molecule-l-carnitine-could serve
as a promising CPA for solvent-free cryopreservation. We demonstrated that l
carnitine possessed strong ability to depress water freezing point, and with
ultrarapid freezing protocol, we studied the post-thaw survival efficiency of
four cell lines (GLC-82 cells, MCF-7 cells, NIH-3T3 cells and Sheep Red Blood
Cells) using l-carnitine without addition of any organic solvents. At the optimum
l-carnitine concentration, all four cell lines could achieve above 80% survival
efficiency, compared with the significantly lower efficiency using organic CPAs
and trehalose. After cryopreservation, the recovered cell behaviors including
cell attachment and proliferation were found to be similar to the normal cells,
indicating that the cell functionalities were not affected. Moreover, l-carnitine
showed no observable cytotoxicity, which was superior to the organic CPAs. This
work offered an attractive alternative to traditional CPAs and held great promise
to revolutionize current cryopreservation technologies, to benefit the patients
in various cell-based clinical applications.
PMID- 28499876
TI - MR imaging for accurate prediction of outcome after perinatal arterial ischemic
stroke: Sooner not necessarily better.
AB - BACKGROUND: Involvement of the corticospinal tracts after perinatal arterial
ischemic stroke (PAIS) is strongly correlated with adverse motor outcome.
METHODS: Two full-term infants with PAIS, with two early MRI scans available, are
reported. RESULTS: Diffusion weighted imaging (DWI)-MRI, performed within 24 h
following onset of seizures and repeated 48 h later, clearly showed restricted
diffusion within the middle cerebral artery territory on both MRIs, but clear
patterns of signal intensity changes in the descending corticospinal tracts on
the second MRI only. CONCLUSION: Since involvement of the corticospinal tracts is
essential for prediction of motor outcome, we may need to reconsider optimal
timing of MR imaging for prediction of neurodevelopmental outcome after PAIS.
PMID- 28499877
TI - Novel Superparamagnetic Microdevices Based on Magnetized PLGA/PLA Microparticles
Obtained by Supercritical Fluid Emulsion and Coating by Carboxybetaine
Functionalized Chitosan Allowing the Tuneable Release of Therapeutics.
AB - When superparamagnetic nanoparticles (MAG) are loaded within microcarriers of
thermosensitive and injectable biopolymers, "smart" microdevices are obtained:
they respond to an external magnetic field through the release of any co
encapsulated molecules with a remote on-off control. Creating reliable and
effective fabrication technologies for the production of these smart
nano/microdevices remains a challenge. In this work, supercritical emulsion
extraction technology is proposed for the fabrication of microcapsules with a
core of poly-lactic-co-glycolic acid (PLGA) or polylactic acid (PLA) covered by
carboxybetaine-functionalized chitosan (f-chi) and loaded with MAG (mean size of
6.5 +/- 3.0 nm) and water-soluble fluorescein (Fluo). Fluo is co-encapsulated as
a fluorescent marker for the release study. Microcarriers showed a mean size of
800 +/- 60 nm with an encapsulation efficiency of up to 90%. The inversion of
surface charge, after the f-chi coating, suggested the presence of a uniform
functionalized surface available for further chemical linkage. The external
chitosan layer had a thickness of 200 +/- 50 nm. An excellent MAG dispersion was
confirmed within the biopolymer matrix that was shown to be responsive to
external magnetic field; indeed, Fluo was released over 3 or 5 days from PLGA or
f-chi-PLGA microdevices into phosphate-buffered saline medium at 37 degrees C,
whereas remote on-off controlled release was achieved when an alternating
magnetic field was applied.
PMID- 28499878
TI - Possible Role of Organic Cation Transporters in the Distribution of
[11C]Sulpiride, a Dopamine D2 Receptor Antagonist.
AB - We synthesized [11C]sulpiride as a positron emission tomography probe for
investigating the drug distribution in the human body. [11C]Sulpiride was
injected to healthy male subjects in either tracer dose of [11C]sulpiride
(approximately 222 MBq) or with therapeutic dose of sulpiride (500 mg, peroral) 3
h before the injection in a crossover fashion. Whole-body positron emission
tomography imaging demonstrated that [11C]sulpiride accumulated exceedingly in
the bladder, followed by liver, gall bladder, and kidney, respectively, at 30 min
after the injection, whereas scarcely in the brain. Oral dose of sulpiride
decreased the hepatic accumulation of the radioactivity by 60%. From in vitro
experiments, we found that sulpiride is a substrate of hOCT1 (Km 2.6 MUM), hOCT2
(Km 68 MUM), hMATE1 (Km 40 MUM), and hMATE2-K (Km 60 MUM). Moreover, the uptake
of sulpiride by human hepatocytes was diminished by tetraethylammonium, and
saturable with Km of 18 MUM. Oct1/2 double knockout mice and wild-type mice
received Mate1 inhibitors (pyrimethamine/cimetidine) manifested reduced renal
clearance of sulpiride, accompanied with its accumulation in the plasma. In
conclusion, we found that sulpiride is a substrate of OCT1, OCT2, MATE1, and
MATE2-K, and this suggests that [11C]sulpiride would be a useful radioligand to
investigate the organic cation transporters in humans.
PMID- 28499879
TI - Developing a Flexible Pediatric Dosage Form for Antiretroviral Therapy: A Fast
Dissolving Tablet.
AB - Current presentations of the anti-HIV drugs lopinavir and ritonavir make
appropriate dosing for children difficult. We conducted a feasibility study to
develop a formulation for these drugs with child-safe excipients in a flexible
dosage form for children across the pediatric age spectrum. The freeze-drying in
blister approach was used to produce fast-dissolving tablets (FDTs), as these can
be dispersed in fluids for easy administration, even to infants, and appropriate
portions of the dispersion can be given for different ages/weights. We combined
various ratios of polymers, surfactants, and bulking agents to incorporate the 2
highly hydrophobic drugs while maintaining drug stability, rapid disintegration,
and good handling properties. The final FDT was robust and disintegrated in 0.5
mL of fluid in 10 s with up to 4 tablets dissolving in 2 mL to achieve varying
doses accommodated in a common teaspoon. Drug recovery after dissolution in small
volumes of liquid or fluid foods was 90%-105%. The final candidate FDT was stable
at 40 degrees C, 75% relative humidity for up to 3 months. FDTs are a promising
flexible dosage form for antiretroviral treatment for pediatric patients,
especially in low-resource settings.
PMID- 28499880
TI - Photoprotection strategies of the alga Nannochloropsis gaditana.
AB - Nannochloropsis spp. are algae with high potential for biotechnological
applications due to their capacity to accumulate lipids. However, little is known
about their photosynthetic apparatus and acclimation/photoprotective strategies.
In this work, we studied the mechanisms of non-photochemical quenching (NPQ), the
fast response to high light stress, in Nannochloropsis gaditana by "locking" the
cells in six different states during quenching activation and relaxation.
Combining biochemical analysis with time-resolved fluorescence spectroscopy, we
correlated each NPQ state with the presence of two well-known NPQ components: de
epoxidized xanthophylls and stress-related antenna proteins (LHCXs). We
demonstrated that after exposure to strong light, the rapid quenching that takes
place in the antennas of both photosystems was associated with the presence of
LHCXs. At later stages, quenching occurs mainly in the antennas of PSII and
correlates with the amount of de-epoxidised xanthophylls. We also observed
changes in the distribution of excitation energy between photosystems, which
suggests redistribution of excitation between photosystems as part of the photo
protective strategy. A multistep model for NPQ induction and relaxation in N.
gaditana is discussed.
PMID- 28499881
TI - Spectral dependence of irreversible light-induced fluorescence quenching:
Chlorophyll forms with maximal emission at 700-702 and 705-710nm as spectroscopic
markers of conformational changes in the core complex.
AB - The spectral dependence of the irreversible non-photochemical fluorescence
quenching associated with photoinhibition in vitro has been comparatively
investigated in thylakoid membranes, PSII enriched particles and PSII core
complexes isolated from spinach. The analysis of the fluorescence emission
spectra of dark-adapted and quenched samples as a function of the detection
temperature in the 280-80K interval, indicates that Chlorophyll spectral forms
having maximal emission in the 700-702nm and 705-710nm ranges gain relative
intensity in concomitance with the establishment of irreversible light-induced
quenching, acting thereby as spectroscopic markers. The relative enhancement of
the 700-702nm and 705-710nm forms emission could be due either to an increase of
their stoichiometric abundance or to their intrinsically low fluorescence quantum
yields. These two factors, that can also coexist, need to be promoted by light
induced alterations in chromophore-protein as well as chromophore-chromophore
interactions. The bands centred at about 701 and 706nm are also observed in the
PSII core complex, suggesting their, at least partial, localisation in proximity
to the reaction centre, and the occurrence of light-induced conformational
changes in the core subunits.
PMID- 28499883
TI - The role of 5-hydroxymethylcytosine in development, aging and age-related
diseases.
AB - DNA methylation at the fifth position of cytosines (5mC) represents a major
epigenetic modification in mammals. The recent discovery of 5
hydroxymethylcytosine (5hmC), resulting from 5mC oxidation, is redefining our
view of the epigenome, as multiple studies indicate that 5hmC is not simply an
intermediate of DNA demethylation, but a genuine epigenetic mark that may play an
important functional role in gene regulation. Currently, the availability of
platforms that discriminates between the presence of 5mC and 5hmC at single-base
resolution is starting to shed light on the functions of 5hmC. In this review, we
provide an overview of the genomic distribution of 5hmC, and examine recent
findings on the role of this mark and the potential consequences of its
misregulation during three fundamental biological processes: cell
differentiation, cancer and aging.
PMID- 28499882
TI - [Effect of several methods of scarification and osmotic stress on seed
germination of Robinia pseudoacacia L.]
AB - The planting of several species adapted to forests areas in the Saharan Atlas
would allow one to better fight against the desertification of the vegetation
cover of these fragile areas. Thanks to its rapid growth on degraded soils,
Robinia pseudoacacia L. has an advantage in the repopulation of these areas
undergoing desertification. Operation of this large-scale tree requires good
control of germination conditions and growth of plants. The scarification of the
seeds of Robinia pseudoacacia L. is necessary to allow the absorption of water by
the seeds. Our results show that mechanical scarification with sulphuric acid
(75minutes), boiling water (90minutes) and scarification by microwaves (700W)
(105seconds) give the best germination rates. The presence of PEG6000 in the
imbibition's solutions reduces considerably the germination rate of the seeds of
R. pseudoacacia L. A 70 % decrease in the optimal rate of germination is observed
when the osmotic pressure of the imbibition solution is at -4.65 bar.
PMID- 28499884
TI - Inhibition of ubiquitin-specific protease 34 (USP34) induces epithelial
mesenchymal transition and promotes stemness in mammary epithelial cells.
AB - Ubiquitin-specific protease 34 (USP34) is a deubiquitinating enzyme that
regulates Axin stability and plays a critical role in Wnt/beta-catenin signaling.
We sought to investigate the role of USP34 on epithelial-mesenchymal (EMT)
induction and its effects on mammary epithelial stem cells. USP34 expression
levels were relatively lower in MDA-MB-231 and 4T1 mesenchymal-like cells when
compared to epithelial-like cells. Inhibition of USP34 in NMuMG cells induced
EMT, as evidenced by the upregulation of EMT markers including N-cadherin,
phospho-Smad3, Snail and active-beta-catenin, as well as the downregulation of
Axin 1 and E-cadherin. USP34 knockdown (KD) in these cells also resulted in the
acquisition of invasive behavior, and promoted stemness as indicated by enhanced
mammosphere-forming ability, concomitant with the upregulation of Nanog, Oct4 and
Sox2 mRNA expression. Endogenous USP34 expression was observed to be at low
levels in virgin mouse mammary glands in vivo. When USP34-KD cells were
transplanted into the cleared mammary fat pads (CFP) of mice, these cells
reconstituted the mammary gland with ductal tree development within 3months. Our
findings suggest a previously unknown role for USP34 in mammary gland
development.
PMID- 28499886
TI - Ambulatory surgery for sleeve gastrectomy: terminology and concept.
PMID- 28499885
TI - The role of GILZ in modulation of adaptive immunity in a murine model of
myocardial infarction.
AB - Myocardial infarction (MI) is associated with intense immune and inflammatory
responses which contribute to tissue injury. Increasing evidence indicates that
the glucocorticoid-induced leucine zipper (GILZ) protein suppresses immune and
inflammatory responses. However, the status of and the role of GILZ in MI are not
known. We tested the hypotheses that a) MI reduces cardiac GILZ associated with
intense inflammation and cell death and b) intramyocardial GILZ delivery confers
cardioprotection in association with increased Tregs and suppression of
inflammation. Male Balb/C mice were subjected to MI or sham operation; the
infarcted animals were subdivided to receive intramyocardial injections of PBS,
GILZ overexpressing cells (GILZ) or their controls expressing the green
fluorescent protein (GFP). Three hours after the procedures, hearts were procured
for subsequent analyses. MI markedly reduced cardiac GILZ expression accompanied
with a) increase in Th-17 cells (i.e., CD3+CD4+IL-17+ BNP-) but decrease in Tregs
(i.e., CD3+CD4+FoxP3+BNP-), and b) disruption of mitochondrial membrane potential
(psim) associated with significant increases in apoptotic and necrotic cell
death. While both GILZ and GFP returned the aforementioned parameters towards
those of sham controls, these effects were most marked for mice receiving GILZ.
Thus, GILZ markedly reduced Th-17 cells but increased Tregs and the anti
inflammatory cytokine, IL-10 positive cells accompanied with preservation of psim
and prevention of cell death. To our knowledge, this is the first report
indicating an important role for GILZ in MI, in part via modulation of adaptive
immune response, which raises the prospect of exogenous GILZ delivery as a novel
cardioprotective modality.
PMID- 28499887
TI - What is the impact on the healthcare system if access to bariatric surgery is
delayed?
AB - BACKGROUND: Bariatric surgery has been available as part of the Brazilian Public
Health System for patients with body mass index>40 kg/m2 (or>35 kg/m2 with co
morbidities) since 1999. However, access to surgery is challenging, with eligible
patients waiting up to 7 years before surgery. OBJECTIVE: Our objective was to
compare costs and effectiveness of different waiting times before surgery versus
prompt surgery. SETTINGS: Public practice. METHODS: A Markov microsimulation
model compared 5 different strategies: no surgery, prompt surgery, and delaying
surgery for 1, 2, 4, and 7 years. Markov tracker variables and states reflected
changes in body mass index, type 2 diabetes status (including remission and
relapse), and cardiovascular events. Time horizon was 20 years; discount rate,
5%; and the perspective of the Brazilian Public Health System. Effectiveness was
calculated as quality adjusted life years. RESULTS: Prompt surgery was the least
costly and most effective strategy compared with any delay. Costs increased and
effectiveness diminished progressively with the length of delays. Waiting 7 years
for surgery was the most expensive and least effective strategy. Prompt surgery
maintained dominance in 99.9%, 90.7%, 96.1%, and 94.2% of simulations in
probabilistic sensitivity analyses versus 1-, 2-, 4-, and 7-year delays,
respectively. Immediate surgery was very cost effective compared with no surgery
in the case base. In the scenario with all patients having type 2 diabetes,
immediate surgery was dominant to any strategy, including the no surgery group.
CONCLUSIONS: Delaying bariatric operations is more expensive and less effective
compared with prompt surgery and very cost effective compared with no surgery.
Public health systems should pursue strategies to accelerate access to surgery to
decrease obesity related complications and mortality of patients, but also to
improve cost effectiveness.
PMID- 28499888
TI - Almeria spatial memory recognition test (ASMRT): Gender differences emerged in a
new passive spatial task.
AB - Many different human spatial memory tasks were developed in the last two decades.
Virtual reality based tasks make possible developing different scenarios and
situations to assess spatial orientation but sometimes these tasks are complex
for specific populations like children and older-adults. A new spatial task with
a very limited technological requirement was developed in this study. It demanded
the use of spatial memory for an accurate solution. It also proved to be
sensitive to gender differences, with men outperforming women under high specific
difficulty levels. Thanks to its simplicity it could be applied as a screening
test and is easy to combine with EEG and fMRI studies.
PMID- 28499890
TI - Interleukin-6 pathway blockade as an option for managing refractory cases of
crystal arthritis: Two cases report.
PMID- 28499889
TI - Recent advances in epilepsy genetics.
AB - In last few years there has been rapid increase in the knowledge of epilepsy
genetics. Nowadays, it is estimated that genetic epilepsies include over than 30%
of all epilepsy syndromes. Several genetic tests are now available for diagnostic
purposes in clinical practice. In particular, next-generation sequencing has
proven to be effective in revealing gene mutations causing epilepsies in up to a
third of the patients. This has lead also to functional studies that have given
insight into disease pathophysiology and consequently to the identification of
potential therapeutic targets opening the way of precision medicine for epilepsy
patients. This minireview is focused on the most recent advances in genetics of
epilepsies. We will also overview the modern genomic technologies and illustrate
the diagnostic pathways in patients with genetic epilepsies. Finally, the
potential implications for a personalized treatment (precision medicine) are also
discussed.
PMID- 28499891
TI - SAPHO, autophagy, IL-1, FoxO1, and Propionibacterium (Cutibacterium) acnes.
AB - Overt infection by Propionibacterium acnes is lacking in many SAPHO syndromes,
and antibiotics have only a transient and incomplete effect, either in SAPHO
syndrome or acne. As several auto-inflammatory bone disorders sharing
overproduction of IL-1beta can mimic SAPHO, this syndrome could partly depend on
genetically encoded overproduction of IL-1beta. However, cyclic intracellular
infections, mostly by P. acnes, can contribute to the enhanced IL-1beta release
by some skin cells, and probably by bone cells. P. acnes is indeed a powerful
trigger of NLRP3-inflammasome activation and IL-1beta, leading to osteitis and
enhanced mesenchymal cells differentiation in osteoblasts. Recent advances in the
understanding of acne suggest that first steps of this disorder are not driven by
P. acnes, but by a relative deficiency of FoxO1 within the nucleus of sebaceous
cells. A similar defect of FoXO1 in bone cells should also be sought in SAPHO,
since repression of FoxO1 gene is found in lesional psoriasis skin, and is
associated with an increased number of osteoblasts and high bone mass in mice.
FoxO1 selectively promotes IL-1beta production, so that its downregulation could
help some P. acnes t escape innate immunity and persist in a latent state in bone
cells, including mesenchymal stem cells. However, P. acnes itself possibly
contributes to FoxO1 downregulation, like H. pylori infection which induces
nuclear inactivation of FoxO1 in human gastric cells to slow down autophagic
clearance. As bisphosphonates, which often improve SAPHO syndromes, enhance
autophagy, it may be worth testing whether their combination with antibiotics is
synergistic in SAPHO syndromes.
PMID- 28499892
TI - Tocilizumab for giant cell arteritis with corticosteroid-resistant progressive
anterior ischemic optic neuropathy.
AB - BACKGROUND: Giant cell arteritis is an inflammatory disorder of the medium- and
large-size arteries. Permanent visual loss related to arteritic anterior ischemic
optic neuropathy is among the most serious complications of this disease and
initial treatment usually consists of high dose corticosteroids. There is no
consensus in the literature concerning the optimal therapeutic approach in giant
cell arteritis patients with corticosteroid-resistant arteritic anterior ischemic
optic neuropathy. CASE REPORT: A 73-year-old Caucasian female with biopsy-proven
giant cell arteritis developed an acute visual loss of the right eye due to
arteritic anterior ischemic optic neuropathy. Despite 5 daily methylprednisolone
pulses, systemic symptoms persisted and rapid involvement of the controlateral
eye was documented. Therefore, tocilizumab (humanised monoclonal antibody binding
the human interleukin-6 receptor) was introduced as a potential salvage therapy
with a swift consecutive resolution of the systemic symptoms and stabilization of
the ophthalmic lesions. CONCLUSIONS: Although a late effect of steroids pulses
cannot be formally ruled out in this dramatic situation, tocilizumab likely
offered a decisive effect in preventing bilateral blindness and may have
contributed to steroid tapering. Tocilizumab may represent a new early effective
second-line treatment option in corticosteroid-resistant anterior ischemic optic
neuropathy. More data are needed to confirm this observation and to evaluate the
safety profile of this treatment.
PMID- 28499893
TI - Vertebroplasty and interventional radiology procedures for bone metastases.
AB - Advances in cancer treatments have lengthened the survival of patients with bone
metastases. Optimal control of the symptoms and prevention of the complications
associated with bone metastases improve quality of life. Achieving these goals
increasingly involves interventional radiology procedures. These include bone
consolidation and analgesic techniques such as cementoplasty (vertebroplasty at
the spine); percutaneous implantation of screws, metallic reinforcement devices,
or intraosseous implants; and tumor destruction using thermal methods
(radiofrequency and cryotherapy), chemicals (alcohol), and drugs
(chemoembolization), which have fewer indications. Here, these techniques and
their indications are reviewed.
PMID- 28499895
TI - Epstein-Barr virus and rheumatoid arthritis.
AB - Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, with a
0.5% worldwide prevalence. The cause of RA remains unknown, however both genetic
and environmental factors may contribute to its development. Among these is the
Epstein-Barr virus (EBV). Here, we discuss several aspects of the close
relationship between EBV and RA. Patients with RA have impaired control of EBV
infection. Indeed, they have high titres of antibodies against EBV antigens.
Their peripheral blood T lymphocytes are less efficient at controlling the
outgrowth of EBV-infected B cells. RA patients have more EBV-infected B cells
than normal controls, leading to a 10-fold systemic EBV overload. Post-transplant
lymphoproliferative disorder (PTLPD) is a polyclonal EBV-positive B lymphocyte
proliferation, which can evolve into an EBV-positive B cell lymphoma. RA patients
also have an increased risk of developing EBV-associated lymphoproliferative
disorder (LPD). Hence the need to monitor EBV load when treating RA patients with
immunosuppressors. EBV, a widespread virus, highly recognized by antibodies but
never eliminated, is an ideal candidate to trigger chronic immune complex
disease. Anti-EBV antibody responses should be considered as one of the chronic
autoantibody responses linked to the development of RA, in the same way as anti
citrullinated protein antibodies.
PMID- 28499894
TI - Pathophysiology of bone metastases from solid malignancies.
AB - Bone metastases are common complications of many cancers. Among the mechanisms
that set the scene for the development of bone metastases, several are shared by
all forms of metastatic dissemination (pre-metastatic niche formation and
chemotactic attraction of malignant cells, which invade the host tissue) and
others are specific of bone tissue (homing of malignant cells to bone marrow
niches and acquisition of an osteomimetic cell phenotype). After a latency period
that can last several years, the malignant cells can proliferate into tumors that
alter the normal bone remodeling process by inducing dysregulation of osteoblast
and osteoclast function. These metastases may be lytic, characterized by major
bone destruction; sclerotic, with excess bone formation; or mixed. Osteolysis
occurs when the tumor cells stimulate osteoclast activity and inhibit osteoblast
activity, whereas the opposite effects lead to bone sclerosis. Moreover, the
mineralized bone matrix plays a major role in the formation of bone metastases,
as its degradation releases growth factors and calcium that exert mitogenic
effects on tumor cells. Thus, bone metastases are the site of a vicious circle in
which mechanisms involved in bone resorption/formation promote tumor growth and
vice versa.
PMID- 28499896
TI - Decreased prefrontal brain activation during verbal fluency task in patients with
somatoform pain disorder: An exploratory multi-channel near-infrared spectroscopy
study.
AB - BACKGROUND: Pain is a common phenomenon. Patients with somatoform pain disorder
(SPD) suffer from lasting chronic pain which may cause cognitive impairment. The
dysfunction of prefrontal cortex (PFC) may be involved in pain-induced cognition
impairment, which is the most important part in regulating of cognitive function.
Multi-channel near-infrared spectroscopy (NIRS) is a noninvasive and low-cost
functional neuroimaging technique being used to detect the prefrontal cortex
activation during cognitive tasks to demonstrate the relationship between PFC
dysfunction and cognition impairment in SPD patients. METHODS: 24 patients with
SPD and 24 age-, gender- and education level-matched healthy controls were
examined by NIRS of the relative concentration of oxygenated hemoglobin (oxy-Hb)
in PFC during verbal fluency task (VFT). All data analysis procedures were
accomplished under MATLAB, SPM and SPM-fNIRS which is an SPM12-based software for
fNIRS analysis. RESULTS: 1. The number of words generated during the VFT tasks in
SPD patients were fewer than healthy controls. 2. The activated areas in SPD
patients were smaller than healthy controls. 3. The average activation strength
of [oxy-Hb] in SPD patients was much lower than healthy controls. 4. The
difference of activation areas between left and right lobe were particularly
obvious in SPD patients. CONCLUSION: There are evidences suggested that the
markedly dysfunction in PFC especially bilateral dorsolateral prefrontal cortex
(DLPFC) areas may be involved in the cognitive deficiency in patients with SPD.
PMID- 28499897
TI - Reduced language lateralization in first episode schizophrenia: A near infrared
spectroscopy study.
AB - BACKGROUND: Diminished functional lateralization in language-related areas is
found in chronic schizophrenia (SZ). However, whether this reduced lateralization
exists at the early stage of SZ remains unclear. The present study aimed to
investigate language lateralization in first episode schizophrenia (FES) using
near infrared spectroscopy (NIRS) during a letter version of verbal fluency test
(VFT). METHODS: A total of 28 FES patients and 33 healthy controls (HCs)
underwent NIRS while performing a VFT. Six regions of interests (ROIs) were
defined: the bilateral frontal-, inferior frontal gyrus (IFG), and temporal
regions. Laterality index (LI) was calculated and compared between the two groups
in ROIs. In addition, we investigated whether language lateralization was
correlated with severity of clinical symptoms. RESULTS: Across all ROIs, LI was
significantly reduced in FES patients (p=0.037) compared to controls in the IFG
region. In addition, LI was not found to be correlated with VFT performance, the
PANSS positive, negative or general psychopathology subscales. CONCLUSIONS: Our
study demonstrated a diminution of leftward functional lateralization in the IFG
during a VFT in FES patients. This is the first NIRS study to report reduced
functional lateralization in patients at the early stage of schizophrenia.
PMID- 28499898
TI - Antidepressant drugs for beta amyloid-induced depression: A new standpoint?
AB - Mounting evidence suggests that depression represents a risk factor and an early
manifestation of Alzheimer's disease (AD). Neuropsychiatric symptoms may derive
from neurobiological changes in specific brain areas and may be considered
prodromal of dementia. We have previously reported the depressive-like profile in
rats receiving a single intracerebroventricular injection of soluble amyloid beta
protein (betaA). Here, we verified the effect of different classes of
antidepressants on the betaA-induced depressive behavior and on cortical
monoamine levels. To these purposes, the forced swimming test was performed and
cortical levels of serotonin (5-HT) and noradrenaline (NA) were quantified by
high performance liquid chromatography (HPLC). We found that acute fluoxetine
(20mg/kg, s.c.), reboxetine (10mg/kg, s.c.), and ketamine (15mg/kg, i.p.)
significantly reduced the immobility in betaA-treated rats compared to controls.
Fluoxetine and reboxetine reversed 5-HT reduction, while betaA-induced NA
increase was further enhanced by all treatments. Treatments with fluoxetine,
reboxetine and ketamine were able to revert soluble betaA-induced decrease of
cortical BDNF levels, while only fluoxetine and ketamine, but not reboxetine, had
the same effects on cortical NGF expression. Moreover, plasma soluble betaA
levels were lowered by fluoxetine, but not reboxetine and ketamine, treatments.
Our data suggest that different classes of antidepressants yield a short-acting
effect on rat soluble betaA-induced depressive profile. Thus, we hypothesize a
novel common mechanism of action of these drugs also based upon a "betaA
lowering" effect. Although further investigations are still needed, our study
might open a new scenario for unravelling the molecular antidepressant mechanisms
of these drugs.
PMID- 28499899
TI - The wake-promoting drug Modafinil prevents motor impairment in sickness behavior
induced by LPS in mice: Role for dopaminergic D1 receptor.
AB - The wake-promoting drug Modafinil has been used for many years for treatment of
Narcolepsy and Excessive Daytime Sleepiness, due to a dopamine-related
psychostimulant action. Recent studies have indicated that Modafinil prevents
neuroinflammation in animal models. Thus, the aim of the present study was to
evaluate the effect of Modafinil pretreatment in the Lipopolysaccharide (LPS)
induced sickness and depressive-like behaviors. Adult male C57BL/6J mice were
pretreated with Vehicle or Modafinil (90mg/Kg) and, 30min later, received a
single saline or LPS (2mg/Kg) administration, and were submitted to the open
field and elevated plus maze test 2h later. After 24h, mice were subjected to
tail suspension test, followed by either flow cytometry with whole brain for
CD11b+CD45+ cells or qPCR in brain areas for cytokine gene expression. Modafinil
treatment prevented the LPS-induced motor impairment, anxiety-like and depressive
like behaviors, as well as the increase in brain CD11b+CD45high cells induced by
LPS. Our results indicate that Modafinil pretreatment also decreased the IL-1beta
gene upregulation caused by LPS in brain areas, which is possibly correlated with
the preventive behavioral effects. The pharmacological blockage of the
dopaminergic D1R by the drug SCH-23390 counteracted the effect of Modafinil on
locomotion and anxiety-like behavior, but not on depressive-like behavior and
brain immune cells. The dopaminergic D1 receptor signaling is essential to the
Modafinil effects on LPS-induced alterations in locomotion and anxiety, but not
on depression and brain macrophages. This evidence suggests that Modafinil
treatment might be useful to prevent inflammation-related behavioral alterations,
possibly due to a neuroimmune mechanism.
PMID- 28499900
TI - Lurasidone in post-menopausal females with major depressive disorder with mixed
features: Post-hoc analysis of a placebo-controlled trial.
AB - BACKGROUND: Several studies have found that depressed, post-menopausal females
may respond differently to antidepressants compared to pre-menopausal females.
The atypical antipsychotic lurasidone, whose mechanism of action differs from
SSRIs and other standard antidepressants, was shown in a 6-week randomized,
flexible-dose, placebo-controlled study (n=209), to be effective in treating
major depressive disorder (MDD) with mixed features (subthreshold hypomanic
symptoms). This post-hoc analysis assessed the efficacy of lurasidone in this
study by menopausal status. METHODS: The main outcome measure for this post-hoc
analysis was change in MADRS score from baseline to week 6 endpoint for two
lurasidone-treated subgroups: presumptive pre-menopausal (<52years) and
presumptive post-menopausal (>=52years) patients, compared to placebo treatment,
using a mixed-model for repeated-measures analysis, and calculation of the effect
size for each subgroup. Additional efficacy assessments included the CGI-S, HAM-A
and YMRS. An exploratory analysis was also conducted removing presumptive peri
menopausal women (ages 45-51years) to allow for clearer definition of pre- and
post-menopausal status. RESULTS: A total of 56 lurasidone-treated and 47 placebo
treated pre-menopausal females, and 17 lurasidone-treated and 25 placebo-treated
post-menopausal females were available from the larger study for comparison on
key outcome measures. The pre- and post-menopausal subgroups had similar
demographic and clinical characteristics at study baseline (other than age),
including number of past major depressive episodes as well as depressive and
manic symptom severity. Mean daily lurasidone dose was similar for each subgroup
during the study. Both the primary and exploratory analyses showed that both
lurasidone-treated post-menopausal and pre-menopausal females responded
significantly compared to placebo (p=0.016 or less) on the MADRS, and that post
menopausal patients had a numerically larger response (effect size=0.96) than pre
menopausal patients (effect size=0.64). All other secondary outcome measures for
lurasidone compared with placebo treatment were significant (p=0.045 or less) for
both subgroups. CONCLUSIONS: In this post-hoc analysis, lurasidone was found to
be effective in treating post-menopausal MDD patients with mixed features
(subthreshold hypomanic symptoms).
PMID- 28499901
TI - Antioxidant and anti-inflammatory nutrient status, supplementation, and
mechanisms in patients with schizophrenia.
AB - Over 50 million people around the world suffer from schizophrenia, a severe
mental illness characterized by misinterpretation of reality. Although the exact
causes of schizophrenia are still unknown, studies have indicated that
inflammation and oxidative stress may play an important role in the etiology of
the disease. Pro-inflammatory cytokines are crucial for normal central nervous
development and proper functioning of neural networks and neurotransmitters.
Patients with schizophrenia tend to have abnormal immune activation resulting in
elevated pro-inflammatory cytokine levels, ultimately leading to functional brain
impairments. Patients with schizophrenia have also been found to suffer from
oxidative stress, a result of an imbalance between the production of free
radicals and the ability to detoxify their harmful effects. Furthermore,
inflammation and oxidative stress are implicated to be related to the severity of
psychotic symptoms. Several nutrients are known to have anti-inflammatory and
antioxidant functions through various mechanisms in our body. The present review
evaluates studies and literature that address the status and supplementation of
omega-3 polyunsaturated fatty acids, vitamin D, B vitamins (B6, folate, B12),
vitamin E, and carotenoids in different stages of schizophrenia. The possible
anti-inflammatory and antioxidant mechanisms of action of each nutrient are
discussed.
PMID- 28499902
TI - Dumbbell-Shaped Jugular Foramen Tumors Extending to the Neck: Surgical
Considerations Based on Imaging Findings.
AB - OBJECTIVE: Dumbbell-shaped jugular foramen tumors (DSJFTs) extending to the neck
present diagnostic and management difficulties because of their rarity, various
pathologies, and multidisciplinary involvement. Accurate imaging findings are of
great importance for surgical planning and clinical outcomes. However, few
articles have discussed this issue to date. METHODS: Thirty-one patients with
DSJFTs extending to the neck were surgically treated in a single stage at our
institute. Their clinical and radiologic features, operative procedures, and
outcomes were retrospectively reviewed. RESULTS: Preoperative correct diagnosis
of DSJFTs extending to the neck was made in all cases of benign tumor and in only
3 cases of malignant tumors in this series. All tumors were removed via a
craniocervical approach by a multidisciplinary skull base team because of both
their intracranial and neck extensions. Total removal was achieved in 26 patients
(83.9%). Preoperative symptoms were improved in 18 patients, whereas new or
worsening lower cranial nerve deficits occurred in 4 patients postoperatively.
Follow-up (1-132 months, mean 64.4 months) was available in 90.3% of the
patients. No clinical or radiologic signs of tumor recurrence were observed.
CONCLUSIONS: Preoperative radiologic evaluation of DSJFTs extending to the neck
is essential for differential diagnosis, patient selection, and surgical
planning. Favorable surgical outcomes can be achieved via a craniocervical
approach, and some detailed imaging findings are helpful to increase the safety
of tumor resection and reduce the morbidity of lower cranial nerve deficits and
cerebrospinal fluid leakage.
PMID- 28499903
TI - Use of Paine's Technique: Projecting Puncture Point to the Skull and Skin.
AB - OBJECTIVE: Ventriculostomy from Paine's point is an effective technique to ensure
that the brain is relaxed for aneurysm surgery. This study aimed to use Paine's
point for other neurosurgical procedures (except for those that require a
pterional approach) by delineation of surface landmarks for identification of
Paine's point on the cranium and scalp. METHODS: Based on the anatomical
knowledge and examination of 3-dimensional computed tomography images of skull,
we determined novel surface landmarks to identify Paine's point on the cranium
and scalp. The new method was used in patients with intraventricular hemorrhage
and aneurysmal subarachnoid hemorrhage caused by ruptured aneurysm of the
anterior communicating artery. RESULTS: The puncture point was determined at a
point located 2.5 cm superior to the supraorbital margin on linea temporalis on
the skull and 2.5 cm superior to the eyebrow along the anterior edge of temporal
muscle on the skin. Ventriculostomy was performed from Paine's point in patients
with intraventricular hemorrhage or aneurysmal subarachnoid hemorrhage who
underwent aneurysm surgery via an interhemispheric approach. No adverse events
were observed in any of the patients. CONCLUSIONS: By accurate surface marking on
skull and skin, the use of Paine's point for ventriculostomy performed via an
interhemispheric approach or for simple burr-hole surgery was found to be safe
and reliable.
PMID- 28499904
TI - Completely Thrombosed Distal Middle Cerebral Artery Aneurysm Mimicking a
Cavernous Angioma: Case Report and Review of the Literature.
AB - BACKGROUND: Distal middle cerebral artery (MCA) aneurysms originate from branches
of MCA distal to its main bifurcation or the peripheral branches. Distal MCA
aneurysms are uncommon compared with saccular aneurysms, which develop along the
proximal trunks of MCA. However, thrombotic aneurysms, characterized by organized
intraluminal thrombus and solid mass, are frequently in the large and giant size
range, whereas complete thrombosis of non-giant MCA aneurysms is very rare. CASE
PRESENTATION: We present the clinical case of a 53 years-old woman with a
completely thrombosed medium distal MCA aneurysm mimicking a cavernous angioma.
She came to our emergency department after the onset of tinnitus and persistent
headache. Magnetic resonance imaging performed subsequently showed a nodular mass
surrounded by edema located in the temporal lobe with a homogeneous peripheral
contrast enhancement. Furthermore, angiography showed regular flow in the MCA and
confirmed the diagnosis of cavernous angioma. The patient underwent surgery, and
the lesion was found to be a thrombosed aneurysm originating from the distal
temporal branch of the left MCA (M2 segment). CONCLUSIONS: To our knowledge, this
is the first report of a thrombosed distal medium MCA aneurysm that mimicked a
cavernous angioma. The completely thrombosed aneurysm can be confused with
intracranial lesions or cavernous malformations, which can have similar
radiographic features without angiographic anomalies, so it is mandatory to
consider the possibility of a thrombosed aneurysm for a correct differential
diagnosis.
PMID- 28499905
TI - Unholy Alliance, Pathway to Scholarly Work, or Just an Association?
PMID- 28499906
TI - A numerical approach to determine mutant invasion fitness and evolutionary
singular strategies.
AB - We propose a numerical approach to study the invasion fitness of a mutant and to
determine evolutionary singular strategies in evolutionary structured models in
which the competitive exclusion principle holds. Our approach is based on a dual
representation, which consists of the modeling of the small size mutant
population by a stochastic model and the computation of its corresponding
deterministic model. The use of the deterministic model greatly facilitates the
numerical determination of the feasibility of invasion as well as the convergence
stability of the evolutionary singular strategy. Our approach combines standard
adaptive dynamics with the link between the mutant survival criterion in the
stochastic model and the sign of the eigenvalue in the corresponding
deterministic model. We present our method in the context of a mass-structured
individual-based chemostat model. We exploit a previously derived mathematical
relationship between stochastic and deterministic representations of the mutant
population in the chemostat model to derive a general numerical method for
analyzing the invasion fitness in the stochastic models. Our method can be
applied to the broad class of evolutionary models for which a link between the
stochastic and deterministic invasion fitnesses can be established.
PMID- 28499907
TI - Occurrence of ampicillin-resistant Enterococcus faecium carrying esp gene in pet
animals: An upcoming threat for pet lovers.
AB - OBJECTIVES: This study was carried out to investigate oral colonisation by
Enterococcus faecalis and Enterococcus faecium in pet dogs and cats, with special
reference to antibiotic resistance. METHODS: Oral swabs were collected from 63
pet dogs and 57 pet cats with no known history of hospitalisation. All samples
were enriched in Kenner Fecal (KF) broth before being cultured on KF agar to
isolate enterococci. E. faecalis and E. faecium were identified by biochemical
and molecular techniques. Antimicrobial resistance was determined by the disk
diffusion method, and ampicillin-resistant strains were further examined by PCR
to detect the esp gene. RESULTS: Oral prevalence rates of E. faecalis among pet
dogs and cats were 3.2% and 5.3%, respectively, whilst those for E. faecium were
22.2% and 15.8%, respectively. None of the isolated enterococci were resistant to
vancomycin. However, ampicillin-resistant E. faecium (AREfm) was detected in the
examined dogs and cats at rates of 14.3% and 5.3%, respectively. Moreover, among
the isolated enterococci, six isolates showed multidrug resistance (all AREfm).
Whilst the esp gene was detected in only two of nine canine AREfm isolates
(multidrug-resistant strains), none of feline AREfm isolates harboured esp.
CONCLUSIONS: The occurrence of AREfm and the esp gene among oral isolates from
pet dogs and cats represents a great public health hazard for pet owners and
highlights possible zoonotic transmission of such a nosocomial pathogen outside
healthcare facilities.
PMID- 28499908
TI - Identification of novel mammalian hosts and Brazilian biome geographic
distribution of Trypanosoma cruzi TcIII and TcIV.
AB - Trypanosoma cruzi is a parasitic protozoan responsible for Chagas disease. Seven
different Discrete Typing Units (DTUs) of T. cruzi are currently identified in
nature: TcI-TcVI, and TcBat whose distribution patterns in nature,
hosts/reservoirs and eco-epidemiological importance are still little known. Here,
we present novel data on the geographic distribution and diversity of mammalian
hosts and vectors of T. cruzi DTUs TcIII and TcIV. In this study, we analyzed 61
T. cruzi isolates obtained from 18 species of mammals (five orders) and two
Hemiptera genera. Samples were collected from five Brazilian biomes (Pantanal,
Caatinga, Cerrado, Atlantic Rainforest, and Amazon) previously characterized as
Z3 or mixed infection (TcI-Z3) by mini-exon gene PCR. To identify TcIII and TcIV
genotypes, we applied restriction fragment length polymorphism analysis to the
PCR-amplified histone 3 gene. DTUs TcIII and TcIV were identified in single and
mixed infections from wide dispersion throughout five Brazilian biomes studied,
with TcIV being the most common. Pantanal was the biome that displayed the
largest number of samples characterized as TcIII and TcIV in single and mixed
infections, followed by Atlantic Rainforest and Amazon. Species from the
Didelphimorphia order displayed the highest frequency of infection and were found
in all five biomes. We report, for the first time, the infection of a species of
the Artiodactyla order by DTU TcIII. In addition, we describe new host species:
five mammals (marsupials and rodents) and two genera of Hemiptera. Our data
indicate that DTUs TcIII and TcIV are more widespread and infect a larger number
of mammalian species than previously thought. In addition, they are transmitted
in restricted foci and cycles, but in different microhabitats and areas with
distinct ecological profiles. Finally, we show that DTUs TcIII and TcIV do not
present any specific association with biomes or host species.
PMID- 28499909
TI - Sesame oil: An ex vivo study of properties against oxidation of plasma low
density lipoproteins and total serum lipoproteins.
PMID- 28499910
TI - SPARC paucity alleviates superoxide-mediated oxidative stress, apoptosis, and
autophagy in diabetogenic hepatocytes.
AB - Secreted protein acidic and rich in cysteine (SPARC) is known to play a
previously unappreciated role in diabetes, but its precise mechanism in
liver/hepatocyte pathology remains unknown. Inhibition of SPARC is critical in
resolving candidate pathogenic events such as production of reactive oxygen
species (ROS), which are broadly considered for their roles in diabetes, and is
capable of protecting functional hepatocytes. Here, we provide in vitro and in
vivo evidence demonstrating pathological correlations between SPARC and
streptozotocin (STZ)-induced diabetic rat livers as well as cultured hepatocytes
induced by diabetogenic stimuli. Under these conditions, transient SPARC
silencing was carried out to investigate the role of SPARC in the pathogenesis of
pro-diabetic hepatocyte damage and dysfunction. The constitutive expression of
SPARC in hepatocytes was up-regulated under a diabetic environment. In addition,
Nox4-dependent superoxide generation contributed to increased expression of
SPARC, and this was inhibited by tiron and pharmacological or genetic
inactivation of Nox4-containing NADPH oxidase. Remarkably, SPARC deficiency
inhibited diabetic stimuli-induced elevation of superoxide production and
resolved salient features of hepatocyte damage such as impaired cytoprotection,
inflammation, apoptosis, and autophagy. At the same time, links between SPARC,
integrin-beta1, Nox4-derived superoxide, and JNK signaling provide a basis for
these phenotypes. Taken together with the observations that SPARC deficiency had
protective effects on hepatocytes via a favorable inhibition profile, functional
knowledge of SPARC may offer a unique therapeutic approach to preserve
hepatocellular fate decisions in diabetes.
PMID- 28499911
TI - Aging-associated metabolic disorder induces Nox2 activation and oxidative damage
of endothelial function.
AB - Oxidative stress attributable to the activation of a Nox2-containing NADPH
oxidase is involved in the development of vascular diseases and in aging.
However, the mechanism of Nox2 activation in normal aging remains unclear. In
this study, we used age-matched wild-type (WT) and Nox2 knockout (KO) mice at 3-4
months (young); 11-12 months (middle-aged) and 21-22 months (aging) to
investigate age-related metabolic disorders, Nox2 activation and endothelial
dysfunction. Compared to young mice, middle-aged and aging WT mice had
significant hyperglycaemia, hyperinsulinaemia, increased systemic oxidative
stress and higher blood pressure. Endothelium-dependent vessel relaxation to
acetylcholine was significantly impaired in WT aging aortas, and this was
accompanied by increased Nox2 and ICAM-1 expressions, MAPK activation and
decreased insulin receptor expression and signaling. However, these aging
associated disorders were significantly reduced or absent in Nox2KO aging mice.
The effect of metabolic disorder on Nox2 activation and endothelial dysfunction
was further confirmed using high-fat diet-induced obesity and insulin resistance
in middle-aged WT mice treated with apocynin (a Nox2 inhibitor). In vitro
experiments showed that in response to high glucose plus high insulin challenge,
WT coronary microvascular endothelial cells increased significantly the levels of
Nox2 expression, activation of stress signaling pathways and the cells were
senescent, e.g. increased p53 and beta-galactosidase activity. However, these
changes were absent in Nox2KO cells. In conclusion, Nox2 activation in response
to aging-associated hyperglycaemia and hyperinsulinaemia plays a key role in the
oxidative damage of vascular function. Inhibition or knockout of Nox2 preserves
endothelial function and improves global metabolism in old age.
PMID- 28499912
TI - Cyclophosphamide and acrolein induced oxidative stress leading to deterioration
of metaphase II mouse oocyte quality.
AB - Cyclophosphamide (CTX) is a chemotherapeutic agent widely used to treat ovarian,
breast, and hematological cancers as well as autoimmune disorders. Such
chemotherapy is associated with reproductive failure and premature ovarian
insufficiency. The mechanism by which CTX and/or its main metabolite, acrolein,
affect female fertility remains unclear, but it is thought to be caused by an
overproduction of reactive oxygen species (ROS). Here, we investigated the effect
of CTX on metaphase II mouse oocytes obtained from treated animals (120mg/kg, 24h
of single treatment), and oocytes directly exposed to increasing concentrations
of CTX and acrolein (n=480; 0, 5, 10, 25, 50, and 100MUM) with and without
cumulus cells (CCs) for 45min which correlates to the time of maximum peak plasma
concentrations after administration. Oocytes were fixed and subjected to indirect
immunofluorescence and were scored based on microtubule spindle structure (MT)
and chromosomal alignment (CH). Generation of ROS was evaluated using the
Cellular Reactive Oxygen Species Detection Assay Kit. Deterioration of oocyte
quality was noted when oocytes were obtained from CTX treated mice along with CTX
and acrolein treated oocytes in a dose-dependent manner as shown by an increase
in poor scores. Acrolein had an impact at a significantly lower level as compared
to CTX, plateau at 10MUM versus 50MUM, respectively. These variation is are
associated with the higher amount of ROS generated with acrolein exposure as
compared to CTX (p<0.05). Utilization of antioxidant therapy and acrolein
scavengers may mitigate the damaging effects of these compounds and help women
undergoing such treatment.
PMID- 28499913
TI - Integration of gel-based and gel-free proteomic data for functional analysis of
proteins through Soybean Proteome Database.
AB - : The Soybean Proteome Database (SPD) stores data on soybean proteins obtained
with gel-based and gel-free proteomic techniques. The database was constructed to
provide information on proteins for functional analyses. The majority of the data
is focused on soybean (Glycine max 'Enrei'). The growth and yield of soybean are
strongly affected by environmental stresses such as flooding. The database was
originally constructed using data on soybean proteins separated by two
dimensional polyacrylamide gel electrophoresis, which is a gel-based proteomic
technique. Since 2015, the database has been expanded to incorporate data
obtained by label-free mass spectrometry-based quantitative proteomics, which is
a gel-free proteomic technique. Here, the portions of the database consisting of
gel-free proteomic data are described. The gel-free proteomic database contains
39,212 proteins identified in 63 sample sets, such as temporal and organ-specific
samples of soybean plants grown under flooding stress or non-stressed conditions.
In addition, data on organellar proteins identified in mitochondria, nuclei, and
endoplasmic reticulum are stored. Furthermore, the database integrates multiple
omics data such as genomics, transcriptomics, metabolomics, and proteomics. The
SPD database is accessible at http://proteome.dc.affrc.go.jp/Soybean/. BIOLOGICAL
SIGNIFICANCE: The Soybean Proteome Database stores data obtained from both gel
based and gel-free proteomic techniques. The gel-free proteomic database
comprises 39,212 proteins identified in 63 sample sets, such as different organs
of soybean plants grown under flooding stress or non-stressed conditions in a
time-dependent manner. In addition, organellar proteins identified in
mitochondria, nuclei, and endoplasmic reticulum are stored in the gel-free
proteomics database. A total of 44,704 proteins, including 5490 proteins
identified using a gel-based proteomic technique, are stored in the SPD. It
accounts for approximately 80% of all predicted proteins from genome sequences,
though there are over lapped proteins. Based on the demonstrated application of
data stored in the database for functional analyses, it is suggested that these
data will be useful for analyses of biological mechanisms in soybean.
Furthermore, coupled with recent advances in information and communication
technology, the usefulness of this database would increase in the analyses of
biological mechanisms.
PMID- 28499914
TI - Advances in understanding the pathophysiology of autism spectrum disorders.
AB - Autism spectrum disorders (ASD) are common heterogeneous neurodevelopmental
disorders with typical triad of symptoms: impaired social interaction, language
and communication abnormalities and stereotypical behavior. Despite extensive
research, the etiology and pathogenesis of ASD remain largely unclear. The lack
of solid knowledge on the mechanisms of these disorders decreases the
opportunities for pathogenetic treatment of autism. Various theories where
proposed in order to explain the pathophysiology underlying ASD. Despite the fact
that none of them is able to completely explain the impairments in the nervous
system of ASD patients, these hypotheses were instrumental in highlighting the
most important mechanisms in the development of this complex disorder. Some new
theories are based on neurovisualization studies, others on the data from genomic
studies, which become increasingly available worldwide. As the research in this
field is largely dependent on the animal models, there is an ongoing discussion
and search for the most appropriate one adequately reproducing the pathology.
Here we provide an overview of current theories of the origin and development of
ASD discussed in the context of existing and proposed rodent models of ASD.
PMID- 28499915
TI - Early life stress and later peer distress on depressive behavior in adolescent
female rats: Effects of a novel intervention on GABA and D2 receptors.
AB - Early life adversity (ELA) increases the risk of depression during adolescence
that may result from a decline in parvalbumin (PVB) secondary to increased
neuroinflammation. In this study, we investigated depressive-like behavior
following exposure to two different types of stressors that are relevant for
their developmental period: 1) chronic ELA (maternal separation; MS) and 2) an
acute emotional stressor during adolescence (witnessing their peers receive
multiple shocks; WIT), and their interaction. We also determined whether reducing
inflammation by cyclooxygenase-2 (COX-2) inhibition would prevent the onset of
depressive-like behavior. Female Sprague-Dawley rat pups underwent MS for four
hours/day or received typical care (CON) between postnatal days (P) 2 and P20. A
COX-2 inhibitor (COX-2I) or vehicle was administered every other day between P30
and P38. Subjects were tested for learned helplessness to assess depressive-like
behavior at P40 (adolescence). MS females demonstrated increased escape latency
and decreased PVB in the prefrontal cortex (PFC) and dorsal raphe that were
attenuated by COX-2I intervention. Helplessness was also associated with an
increase in D2 receptors in the accumbens. In contrast, WIT elevated escape
latency in CON, but reduced latency in MS females. Furthermore, COX-2I
intervention decreased escape latency in both CON and MS after WIT. WIT reduced
PVB levels in the basolateral amygdala and increased PFC levels to CON levels.
Our data suggest that decreased PVB in the PFC is important for the expression of
depressive-like behavior and suggest that COX-2I intervention may provide a novel
prevention for depression.
PMID- 28499916
TI - Effects of neonatal and adolescent neuroactive steroid manipulation on locomotor
activity induced by ethanol in male wistar rats.
AB - Neonatal neuroactive steroids levels are crucial for brain development.
Alterations of neonatal neuroactive steroids levels induce anxiolytic-like
effects and improve exploration in novel environments in adulthood. These
behavioural traits, i.e. sensation/novelty seeking, anxiety or impulsivity, are
associated with vulnerability to drug use and abuse. Adolescence is also
recognized as a particularly critical developmental phase to contribute to
vulnerable phenotype. However, the influence of neuroactive steroids during
development in the vulnerability to drug addiction has been poorly studied. The
aim of the present experiment is to study the effect of early neonatal and
adolescent manipulations of neuroactive steroids on the sensitivity to the
stimulant effects of ethanol in adult male rats. Therefore, allopregnanolone or
finasteride, an allopregnanolone synthesis inhibitor, were injected from
postnatal day 5-9. In early adolescence, half of the subjects were injected with
progesterone, the main allopregnanolone precursor, and the elevated plus-maze
anxiety test was performed. Results indicated that early adolescent progesterone
induced anxiolytic-like effects (increase in the percentage of entries and time
in open arms). Neonatal finasteride administration decreased locomotor activity
induced by ethanol in adolescent vehicle subjects. Interestingly, differences
induced by neonatal treatments were not present in the animals that received
progesterone in the early adolescence. In conclusion, neuroactive steroid
manipulations in crucial stages of development could be playing an important role
in behavioural effects of alcohol such as the sensitivity to locomotor
stimulation.
PMID- 28499917
TI - The role of matrix metalloproteinases in aging: Tissue remodeling and beyond.
AB - Proteases are a set of enzymes that have been involved in multiple biological
processes throughout evolution. Among them, extracellular matrix (ECM) remodeling
has emerged as one of the most relevant functions exerted by these proteins,
being essential in the regulation of critical events such as embryonic
development or tissue homeostasis. Hence, it is not surprising that dysregulation
in any protease function that affects ECM homeostasis may contribute to the aging
process. Matrix metalloproteinases (MMPs) are one of the most important families
of proteases involved in the tight control of ECM remodeling over time. In this
review, we will discuss how MMPs and other proteases alter ECM composition and
mechanical properties in aging, thereby affecting stem cell niches and the
development of senescent phenotypes. Finally, we will summarize recent findings
that associate MMPs with the development of age-related diseases, such as
neurodegenerative disorders.
PMID- 28499918
TI - Cul3 neddylation is crucial for gradual lipid droplet formation during
adipogenesis.
AB - Cullin 3 (Cul3) belongs to the family of cullins (Cul1-7) providing the scaffold
for cullin-RING ubiquitin (Ub) ligases (CRLs), which are activated by neddylation
and represent essential E3 ligases of the Ub proteasome system. During adipogenic
differentiation neddylated Cul3 accumulates in LiSa-2 preadipocytes.
Downregulation of Cul3 and inhibition of neddylation by MLN4924 blocks the
formation of lipid droplets (LDs), the lipid storage organelles and markers of
adipogenesis. Neddylation of Cul3 coincides with an increase of Rab18, a GTPase
associated with LDs. Immunoprecipitation and confocal fluorescence microscopy
revealed physical association of Cul3 and Rab18 at the membrane of LDs. RhoA, a
suppressor of adipogenesis decreased during differentiation. Our results in LiSa
2 cells, but also mouse embryonic fibroblasts revealed a connection between Cul3,
Rab18 and RhoA. Downregulation of Cul3 led to a marked increase in RhoA protein
expression after 6days of LiSa-2 cell differentiation, suggesting that Cul3 is
involved in the regulation of RhoA stability.
PMID- 28499920
TI - Patient Understanding, Expectations, and Satisfaction Regarding Rotator Cuff
Injuries and Surgical Management.
AB - Rotator cuff injuries are among the most common in orthopaedics, with rotator
cuff repair surgery consistently reported as one of the most commonly performed
orthopaedic procedures. Patient satisfaction is becoming an increasingly
important outcome metric as health care continues to evolve with regard to
quality measures affecting physician reimbursement. Evidence supports that
postoperative patient satisfaction, an important quality outcome metric, is
highly influenced by preoperative patient expectations, which are in turn
governed by patient knowledge and understanding. Many authors have delineated
patient-, injury-, and surgery-specific variables associated with high
preoperative expectations and satisfaction after rotator cuff surgery.
Specifically, large rotator cuff tears, subscapularis tears, persistence of
postoperative pain and dysfunction, worker's compensation cases, lower education
level, and preoperative disability have been seen more frequently in patients
reporting poor satisfaction. Others have reported variables associated with
higher patient satisfaction such as being married, employed, and of older age at
the time of surgery (>55 years old) predictive of higher satisfaction. Patient
education preoperatively regarding details about the surgery and the
postoperative plan both immediately after the procedure and for rehabilitation
are critical in helping set patients' preoperative expectations that have a known
effect on patients' subjective clinical outcomes.
PMID- 28499919
TI - Long non-coding RNA AC023115.3 suppresses chemoresistance of glioblastoma by
reducing autophagy.
AB - Malignant glioma is an aggressive brain cancer that responds poorly to
chemotherapy. However, the molecular mechanism underlying the development of
chemoresistance in glioma is not well-understood. In this study, we show that
long non-coding RNA AC023115.3 is induced by cisplatin in human glioblastoma
cells and that elevated AC023115.3 promotes cisplatin-induced apoptosis by
inhibiting autophagy. Further mechanistic studies revealed that AC023115.3 acts
as a competing endogenous RNA for miR-26a and attenuates the inhibitory effect of
miR-26a on GSK3beta, a proline-directed serine-threonine kinase that promotes the
degradation of Mcl1, leading to an increase in GSK3beta and a decrease in
autophagy. Additionally, we discovered that AC023115.3 improves chemosensitivity
of glioma cells to cisplatin by regulating the miR-26a-GSK3beta-Mcl1 pathway.
Thus, these data indicate that the AC023115.3-miR-26a-GSK3beta signalling axis
plays an important role in reducing the chemoresistance of glioma.
PMID- 28499921
TI - Anterior Cruciate Ligament Soft Tissue Graft Fixation in the Elderly: Is There a
Reason to Use Interference Screws? A Human Cadaver Study.
AB - PURPOSE: To analyze the ultimate failure load, yield load, stiffness, and cyclic
resistance of different anterior cruciate ligament (ACL) soft tissue graft
fixation techniques in osteopenic bone. METHODS: In this study, 24 fresh-frozen
human cadaveric tibiae (mean age 82.6 years; range 56-96; 6 male and 6 female
donors) were used. Quantitative computed tomography was performed to match bone
density. Looped porcine flexor tendon grafts were chosen as ACL graft substitutes
for tibial graft fixation techniques (n = 8 each): (1) hybrid fixation with an
interference screw and extracortical button fixation; (2) extracortical button
fixation; and (3) interference screw fixation. In single cycle mode, constructs
were loaded to failure to evaluate stiffness, yield load, and maximum load. In
cyclic testing, 2,000 cycles (25-100 N) were applied followed by loading to
failure. A 1-way analysis of variance was performed with significance set at P =
.05. RESULTS: Hybrid fixation resulted in significantly higher yield load (283.4
+/- 86.19 N; P = .0037) and maximum load (407.9 +/- 102.3 N; P = .0026) than
interference screw fixation (yield load 176.4 +/- 26.03, max load 231.8 +/- 94.06
N) in elderly bone. Yield load after extracortical button fixation (252.9 +/-
41.97 N; P = .0286) was also higher than that after interference screw fixation,
but stiffness (18.98 +/- 9.154 N/mm; P = .0041) was less than that after hybrid
fixation (37.28 +/- 13.53 N/mm). Of 8 specimens in the interference screw group,
7 did not survive 2,000 cycles and failed by graft slippage, whereas all other
specimens in both other groups survived. CONCLUSIONS: Tibial hybrid fixation of
ACL soft tissue grafts provides less vertical graft movement than extracortical
button fixation and higher primary failure loads than interference screw fixation
in elderly bone. CLINICAL RELEVANCE: In this elderly human joint in vitro model,
tibial hybrid fixation provides biomechanical advantages over other techniques.
Graft fixation with only an interference screw should be avoided in osteopenic
bone.
PMID- 28499922
TI - Critical Analysis of the Lever Test for Diagnosis of Anterior Cruciate Ligament
Insufficiency.
AB - PURPOSE: To critically analyze the "lever test" in detecting anterior cruciate
ligament (ACL) tears and to compare its accuracy with the Lachman, anterior
drawer (AD), and pivot shift tests. METHODS: From June 2014 to June 2015, 91
subjects were analyzed. Inclusion criteria were subjects aged 16 to 60 years,
presenting after a knee injury with subjective swelling, or an objective effusion
and an uninjured normal contralateral knee for comparison. Exclusion criteria
included previous knee ligamentous reconstruction, fracture of the distal femur
or proximal tibia, bilateral knee injuries, or known cruciate ligament tear. The
Lachman, AD, pivot shift, and lever tests were performed in the office by 2 board
certified orthopaedic surgeons with patient awake. Examiners were blinded to the
presence or absence of ACL injury. Magnetic resonance imaging was used to
determine injury. Sensitivity, specificity, and accuracy were evaluated for all 4
tests. Accuracy was compared using chi-square and receiver operator curves.
RESULTS: Average subject age was 28 +/- 11 years (61 males, 30 females). Seventy
one (79%) had ACL tears diagnosed by magnetic resonance imaging. The sensitivity,
specificity, and accuracy of the lever test were 83%, 80%, and 82%, respectively.
Accuracy was not statistically different from the Lachman, AD, and pivot shift
tests (P = .78, .99, .07, respectively). Subanalyses were performed based on the
presence of another ligament tear, timing of injury, and the presence of a
meniscus tear. Although the groups were smaller and thus underpowered, the
results were reported. Neither the presence of another ligament tear nor the
timing of the injury affected accuracy (P = .62 and P = .47); however, the
presence of a meniscus tear decreased its accuracy (P = .003). CONCLUSIONS: The
lever test showed high sensitivity, specificity, and overall accuracy in the
detection of ACL tears. The accuracy of the lever test was not significantly
different from the Lachman, AD, or pivot shift tests. LEVEL OF EVIDENCE: Level
II, prospective comparative study.
PMID- 28499924
TI - Hypercholesterolemia Causes Circadian Dysfunction: A Potential Risk Factor for
Cardiovascular Disease.
AB - Hypercholesterolemia is a well-known risk factor for a wide range of diseases in
developed countries. Here, we report that mice lacking functional LDLR (low
density lipoprotein receptor), an animal model of human familial
hypercholesterolemia, show circadian abnormalities. In free running behavioral
experiments in constant darkness, these mice showed a prolonged active phase and
distinctly bimodal rhythms. Even when the circadian rhythms were entrained by
light and dark cycles, these mice showed a significant attenuation of behavioral
onset intensity at the start of the dark period. Further, we hypothesized that
the combination of hypercholesterolemia and circadian abnormalities may affect
cardiovascular disease progression. To examine this possibility, we generated
LDLR-deficient mice with impaired circadian rhythms by simultaneously introducing
a mutation into Period2, a core clock gene, and found that these mice showed a
significant enlargement of artery plaque area with an increase in inflammatory
cytokine IL-6 levels. These results suggest that circadian dysfunction may be
associated with the development or progression of cardiovascular diseases.
PMID- 28499925
TI - Does Kruppel Like Factor 15 Play an Important Role in the Left Ventricular
Hypertrophy of Patients with Type 2 Diabetes?
PMID- 28499926
TI - Epigenetic Studies of Perinatal Determinants of Later Obesity Link Important, but
Previously Unrelated, Genetic and Epidemiological Findings.
PMID- 28499923
TI - The Atypical Kinase RIOK1 Promotes Tumor Growth and Invasive Behavior.
AB - Despite being overexpressed in different tumor entities, RIO kinases are hardly
characterized in mammalian cells. We investigated the role of these atypical
kinases in different cancer cells. Using isogenic colon-, breast- and lung cancer
cell lines, we demonstrate that knockdown of RIOK1, but not of RIOK2 or RIOK3,
strongly impairs proliferation and invasiveness in conventional and 3D culture
systems. Interestingly, these effects were mainly observed in RAS mutant cancer
cells. In contrast, growth of RAS wildtype Caco-2 and Bcr-Abl-driven K562 cells
is not affected by RIOK1 knockdown, suggesting a specific requirement for RIOK1
in the context of oncogenic RAS signaling. Furthermore, we show that RIOK1
activates NF-kappaB signaling and promotes cell cycle progression. Using
proteomics, we identified the pro-invasive proteins Metadherin and Stathmin1 to
be regulated by RIOK1. Additionally, we demonstrate that RIOK1 promotes lung
colonization in vivo and that RIOK1 is overexpressed in different subtypes of
human lung- and breast cancer. Altogether, our data suggest RIOK1 as a potential
therapeutic target, especially in RAS-driven cancers.
PMID- 28499928
TI - Detection of Ostreid herpesvirus-1 microvariants in healthy Crassostrea gigas
following disease events and their possible role as reservoirs of infection.
AB - Ostreid herpesvirus-1 microvariants (OsHV-1) cause severe mortalities in farmed
Crassostrea gigas in Europe, New Zealand and Australia. Outbreaks are seasonal,
recurring in the warmer months of the year in endemic estuaries. The reference
genotype and microvariant genotypes of OsHV-1 have been previously detected in
the tissues of apparently healthy adult oysters naturally exposed to OsHV-1 in
the field. However, the role of such oysters as reservoirs of infection for
subsequent mortality outbreaks remains unclear. The aims of this study were: (1)
to identify the optimal sample type to use for the detection of OsHV-1 DNA in
apparently healthy C. gigas; and (2) to assess whether live C. gigas maintained
on-farm after an OsHV-1 related mortality event remain infected and could act as
a reservoir host for subsequent outbreaks. OsHV-1 DNA was detected in the
hemolymph, gill, mantle, adductor muscle, gonad and digestive gland of apparently
healthy adult oysters. The likelihood of detecting OsHV-1 DNA in hemolymph was
equivalent to that in gill and mantle, but the odds of detecting OsHV-1 DNA in
hemolymph and gill were more than 8 times that of adductor muscle. Gill had the
highest viral loads. Compared to testing whole gill homogenates, testing snippets
of the gill improved the detection of OsHV-1 DNA by about four fold. The
prevalence of OsHV-1 in gill and mantle was highest after the first season of
OsHV-1 exposure; it then declined to low or negligible levels in the same cohorts
in subsequent seasons, despite repeated seasonal exposure in monitoring lasting
up to 4years. The hemolymph of individually identified oysters was repeatedly
sampled over 15months, and OsHV-1 prevalence declined over that time frame in the
youngest cohort, which had been exposed to OsHV-1 for the first time at the start
of that season. In contrast, the prevalence in two cohorts of older oysters,
which had been exposed to OsHV-1 in prior seasons, was consistently low (<10%).
Viral loads were <104 DNA copies per mg tissue or MUL hemolymph, suggesting that
OsHV-1 was not being maintained at or amplified to high quantities. Therefore,
while OsHV-1 may persist within apparently healthy oysters that have survived an
outbreak of disease, they may not be a major reservoir host for the virus for
subsequent outbreaks. However, further investigation is required to ascertain
whether OsHV-1 replication occurs in surviving oysters, and whether transmission
from them to naive oysters and induction of clinical disease is possible.
PMID- 28499927
TI - Disruption of the Hepcidin/Ferroportin Regulatory System Causes Pulmonary Iron
Overload and Restrictive Lung Disease.
AB - Emerging evidence suggests that pulmonary iron accumulation is implicated in a
spectrum of chronic lung diseases. However, the mechanism(s) involved in
pulmonary iron deposition and its role in the in vivo pathogenesis of lung
diseases remains unknown. Here we show that a point mutation in the murine
ferroportin gene, which causes hereditary hemochromatosis type 4 (Slc40a1C326S),
increases iron levels in alveolar macrophages, epithelial cells lining the
conducting airways and lung parenchyma, and in vascular smooth muscle cells.
Pulmonary iron overload is associated with oxidative stress, restrictive lung
disease with decreased total lung capacity and reduced blood oxygen saturation in
homozygous Slc40a1C326S/C326S mice compared to wild-type controls. These findings
implicate iron in lung pathology, which is so far not considered a classical iron
related disorder.
PMID- 28499929
TI - Reproductive efficiency of entomopathogenic nematodes as scavengers. Are they
able to fight for insect's cadavers?
AB - Entomopathogenic nematodes (EPNs) and their bacterial partners are well-studied
insect pathogens, and their persistence in soils is one of the key parameters for
successful use as biological control agents in agroecosystems. Free-living
bacteriophagous nematodes (FLBNs) in the genus Oscheius, often found in soils,
can interfere in EPN reproduction when exposed to live insect larvae. Both groups
of nematodes can act as facultative scavengers as a survival strategy. Our
hypothesis was that EPNs will reproduce in insect cadavers under FLBN presence,
but their reproductive capacity will be severely limited when competing with
other scavengers for the same niche. We explored the outcome of EPN - Oscheius
interaction by using freeze-killed larvae of Galleria mellonella. The
differential reproduction ability of two EPN species (Steinernema kraussei and
Heterorhabditis megidis), single applied or combined with two FLBNs (Oscheius
onirici or Oscheius tipulae), was evaluated under two different infective
juvenile (IJ) pressure: low (3IJs/host) and high (20IJs/host). EPNs were able to
reproduce in insect cadavers even in the presence of potential scavenger
competitors, although EPN progeny was lower than that recorded in live larvae.
Hence, when a highly susceptible host is available, exploiting cadavers by EPN
might limit the adaptive advantage conferred by the bacteria partner, and might
result in an important trade-off on long-term persistence. Contrary to our
hypothesis, for most of the combinations, there were not evidences of competitive
relationship between both groups of nematodes in freeze-killed larvae, probably
because their interactions are subject to interference by the microbial growth
inside the dead host. Indeed, evidences of possible beneficial effect of FLBN
presence were observed in certain EPN-FLBN treatments compared with single EPN
exposure, highlighting the species-specific and context dependency of these
multitrophic interactions occurring in the soil.
PMID- 28499930
TI - Working memory and attentional bias on reinforcing efficacy of food.
AB - Reinforcing efficacy of food, or the relationship between food prices and
purchasing, is related to obesity status and energy intake in adults. Determining
how to allocate resources for food is a decision making process influenced by
executive functions. Attention to appetitive cues, as well as working memory
capacity, or the ability to flexibly control attention while mentally retaining
information, may be important executive functions involved in food purchasing
decisions. In two studies, we examined how attention bias to food and working
memory capacity are related to reinforcing efficacy of both high energy-dense and
low energy-dense foods. The first study examined 48 women of varying body mass
index (BMI) and found that the relationship between attentional processes and
reinforcing efficacy was moderated by working memory capacity. Those who avoid
food cues and had high working memory capacity had the lowest reinforcing
efficacy, as compared to those with low working memory capacity. Study 2
systematically replicated the methods of study 1 with assessment of maintained
attention in a sample of 48 overweight/obese adults. Results showed the
relationship between maintained attention to food cues and reinforcing efficacy
was moderated by working memory capacity. Those with a maintained attention to
food and high working memory capacity had higher reinforcing efficacy than low
working memory capacity individuals. These studies suggest working memory
capacity moderated the relationship between different aspects of attention and
food reinforcement. Understanding how decision making process are involved in
reinforcing efficacy may help to identify future intervention targets.
PMID- 28499931
TI - Empowered to cook: The crucial role of 'food agency' in making meals.
AB - What makes an individual, on any given occasion, able and willing to prepare a
meal for themselves: that is, to cook? As home cooking has increasingly become
the focus of public-health, nutrition, and policy interventions and campaigns,
the need for a better understanding has become apparent. It is clear that cooking
is not merely a matter of mechanical skill or rote training; beyond this, it is
difficult to explain why similar individuals have such different capacities for
setting and achieving food-related goals. This paper proposes a new paradigm for
cooking and food provisioning - termed "food agency" - that attempts to describe
how an individual's desires form and are enacted in correspondence with social
environments: broadly, agency emerges from the complex interplay of individual
technical skills and cognitive capacities with social and cultural supports and
barriers. Drawing on a close reading of anthropological and sociological research
into cooking, the authors propose that an individual's ability to integrate such
complexity in regard to provisioning - to possess 'food agency' - is crucial.
This argument is supplemented by empirical case studies from a large body of
ethnographic observations and interviews with home cooks from the United States,
conducted over the last decade. Overall, more food agency means the cook is more
empowered to act. Adopting the paradigm of food agency into the consideration of
everyday cooking practices has the potential to support transdisciplinary food
scholarship integrating individual actions within a food system and thus inform
nutrition and public health interventions related to meal preparation.
PMID- 28499932
TI - Dietary customs and food availability shape the preferences for basic tastes: A
cross-cultural study among Polish, Tsimane' and Hadza societies.
AB - Biological significance of food components suggests that preferences for basic
tastes should be similar across cultures. On the other hand, cultural factors
play an important role in diet and can consequently influence individual
preference for food. To date, very few studies have compared basic tastes
preferences among populations of very diverse environmental and cultural
conditions, and research rather did not involve traditional populations for whom
the biological significance of different food components might be the most
pronounced. Hence, our study focused on basic taste preferences in three
populations, covering a broad difference in diet due to environmental and
cultural conditions, market availability, dietary habits and food acquirement: 1)
a modern society (Poles, n = 200), 2) forager-horticulturalists from
Amazon/Bolivia (Tsimane', n = 138), and 3) hunter-gatherers from Tanzania (Hadza,
n = 85). The preferences for basic tastes were measured with sprays containing
supra-threshold levels of sweet, sour, bitter, salty, and umami taste solutions.
We observed several interesting differences between participating societies. We
found that Tsimane' and Polish participants liked the sweet taste more than other
tastes, while Hadza participants liked salty and sour tastes more than the
remaining tastes. Further, Polish people found bitter taste particularly
aversive, which was not observed in the traditional societies. Interestingly, no
cross-cultural differences were observed for relative liking of umami taste - it
was rated closely to neutral by members of all participating societies.
Additionally, Hadza showed a pattern to like basic tastes that are more common to
their current diet than societies with access to different food sources. These
findings demonstrate the impact of diet and market availability on preference for
basic tastes.
PMID- 28499934
TI - Matrine promotes oligodendrocyte development in CNS autoimmunity through the
PI3K/Akt signaling pathway.
AB - AIMS: Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix
Sophorae flavescens, has been recently found to be beneficial in experimental
autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, mainly
through its anti-inflammatory effect. In the present study, we tested the effect
of MAT on ongoing EAE and defined possible mechanisms underlying its effects on
myelination and oligodendrocytes. MAIN METHODS: EAE was induced in C57BL/6 mice
and MAT treatment was started at disease onset. Clinical scores were monitored
daily; spinal cords and the corpus callosum brain region of mice were harvested
on day 23 p.i. for inflammatory infiltration and demyelination of the central
nervous system. Myelin content and the development of oligodendrocytes and their
precursors were determined by immunostaining, and expression of p-Akt, p-mTOR, p
PI3K, and p-P70S6 was determined by Western blot. KEY FINDINGS: MAT effectively
suppressed EAE severity and increased the expression of proteolipid protein, a
myelin protein that is a marker of CNS myelin. MAT treatment largely increased
the number of mature oligodendrocytes, and significantly activated the
PI3K/Akt/mTOR signaling pathway, which is required for oligodendrocyte survival
and axon myelination. SIGNIFICANCE: These findings demonstrate a beneficial
effect of MAT on oligodendrocyte differentiation and myelination during EAE, most
likely through activating the PI3K/Akt/mTOR signaling pathway.
PMID- 28499935
TI - Sub-chronic lead exposure produces beta1-adrenoceptor downregulation decreasing
arterial pressure reactivity in rats.
AB - : Lead is considered a causative factor for hypertension and other cardiovascular
diseases. AIMS: To investigate the effects of sub-chronic lead exposure on blood
pressure reactivity and cardiac beta1-adrenoceptor activity and to evaluate
whether the effects found in vitro are similar to those found in vivo. MAIN
METHODS: Male Wistar rats were randomly distributed into two groups: control rats
(Ct) and rats administered drinking water containing 100ppm lead (Pb) for 30days.
KEY FINDINGS: Blood pressure in the Pb rats increased starting from the first
week of treatment until the end of the study [systolic blood pressure, Ct: 122+/
4 vs. Pb: 143+/-3mmHg; diastolic blood pressure, Ct: 63+/-4 vs. Pb: 84+/-4mmHg].
The heart rate was also increased (Ct: 299+/-11 vs. Pb: 365+/-11bpm), but the
pressure reactivity to phenylephrine was decreased. Losartan and hexamethonium
exhibited a greater reduction in blood pressure of Pb rats than in the Ct rats.
Isoproterenol increased the left ventricular systolic and end-diastolic pressure,
and heart rate only in Ct rats, suggesting that lead induced beta1-adrenoceptor
downregulation. Indomethacin reduced the blood pressure and heart rate in the Pb
rats, suggesting the involvement of cyclooxygenase-derived products (which are
associated with reduced nitric oxide bioavailability) in this process.
SIGNIFICANCE: These findings offer further evidence that the effects of sub
chronic lead exposure in vitro can be reproduced in vivo-even at low
concentrations-thus triggering mechanisms for the development of hypertension.
Therefore, lead should be considered an environmental risk factor for
cardiovascular disease.
PMID- 28499936
TI - Umbilical Cord Blood Transplantation without Antithymocyte Globulin Results in
Similar Survival but Better Quality of Life Compared with Unrelated Peripheral
Blood Stem Cell Transplantation for the Treatment of Acute Leukemia-A
Retrospective Study in China.
AB - Although previous studies have demonstrated improved outcomes in umbilical cord
blood transplantation (UCBT) by omitting antithymocyte globulin (ATG) in the
conditioning regimen, this approach has not been comparatively studied in
unrelated peripheral blood stem cell transplantation (UPBSCT). To compare the
risks and benefits between UCBT without ATG and UPBSCT in patients with acute
leukemia (AL), we conducted a multicenter retrospective study of 79 patients who
underwent UCBT (myeloablative conditioning without ATG) and 96 patients who
underwent UPBSCT (myeloablative conditioning with ATG). The outcomes were graft
failure, neutrophil engraftment, platelet engraftment, acute graft-versus-host
disease (aGVHD), chronic graft-versus-host disease (cGVHD), transplantation
related mortality (TRM), relapse, overall survival (OS), and leukemia-free
survival (LFS). Follow-up was censored on October 31, 2016. Engraftment was
similar between the 2 groups but granulocyte and platelet recovery were slower in
the UCBT group (both P < .001). The incidences of aGVHD, TRM, OS, and LFS were
similar between the 2 groups (all P > .05). Without ATG, the UCBT group displayed
less cGVHD and less moderate and severe cGVHD (P < .001 and P = .004). The
incidences of Epstein-Barr virus viremia and post-transplantation
lymphoproliferative disease were significantly lower in the UCBT group (P < .001
and P = .037). UCBT recipients had higher activity Karnofsky performance scores
and 3-year GVHD-free/relapse-free survival than the UPBSCT group (P = .03 and P =
.04). We observed similar survival when comparing UCBT without ATG and UPBSCT,
but we also observed better quality of life in patients undergoing UCBT without
ATG. We can therefore conclude that patients with primary AL for whom an
appropriate HLA-matched sibling donor is not available could select either UCBT
or UPBSCT.
PMID- 28499937
TI - Haploidentical Allogeneic Hematopoietic Cell Transplantation for Multiple Myeloma
Using Post-Transplantation Cyclophosphamide Graft-versus-Host Disease
Prophylaxis.
AB - Allogeneic (allo) hematopoietic cell transplantation (HCT) currently represents
the only potentially curative therapy for patients affected by multiple myeloma
(MM). Up to 30% of patients in western countries do not have a matched donor.
Haploidentical HCT (haplo-HCT) may be an option, but currently, there are little
available data regarding this treatment. We analyzed survival outcomes of 30
heavily pretreated MM patients who received haplo-HCT with post-transplantation
cyclophosphamide as graft-versus-host-disease (GVHD) prophylaxis. Median
neutrophil and platelet engraftments at day +30 were 87% (95% confidence interval
[CI], 66% to 95%) and 60% (95% CI, 40% to 75%), respectively. The cumulative
incidences of relapse or progression of disease (PD) and nonrelapse mortality at
18 months were 42% (95% CI, 23% to 59%) and 10% (95% CI, 2% to 24%),
respectively. The cumulative incidence of grade II to IV acute GVHD at day +100
was 29% (95% CI, 14% to 47%). The cumulative incidence of chronic GVHD at 18
months was 7% (95% CI, 1% to 21%). With a median follow-up in survivors of 25
months (range, 15 to 73 months), the 18-month progression-free survival (PFS) and
overall survival (OS) were 33% (95% CI, 17% to 50%) and 63% (95% CI, 44% to 78%),
respectively. No differences were observed between peripheral blood and bone
marrow graft in terms of engraftment, GVHD, or PD incidence. Chemorefractory
disease at transplantation was associated with a lower/reduced 18-month PFS (9%
versus 47%, P = .01) and OS (45% versus 74%, P = .03). This was explained by a
higher PD incidence (55% versus 33%, P = .05). In this multicenter study, we
report encouraging results with haplo-HCT for patients with heavily pretreated
MM.
PMID- 28499938
TI - Allogeneic Stem Cell Transplantation in Myelofibrosis.
AB - Myeloproliferative neoplasm (MPN) is a category in the World Health Organization
classification of myeloid tumors. BCR-ABL1-negative MPN is a subcategory that
includes primary myelofibrosis (MF), post-essential thrombocythemia MF, and post
polycythemia vera MF. These disorders are characterized by stem cell-derived
clonal myeloproliferation. Clinically, these diseases present with anemia and
splenomegaly and significant constitutional symptoms such as severe fatigue,
symptoms associated with an enlarged spleen and liver, pruritus, fevers, night
sweats, and bone pain. Multiple treatment options may provide symptom relief and
improved survival; however, allogeneic stem cell transplantation (HCT) remains
the only potentially curative option. The decision for a transplant is based on
patient prognosis, age, comorbidities, and functional status. This review
describes the recent data on various peritransplantation factors and their effect
on outcomes of patients with MF and new therapeutic areas, such as the use and
timing of Janus kinase inhibitors with HCT and gives overall conclusions from the
available data in the published literature.
PMID- 28499939
TI - Respecting death at the coal face.
PMID- 28499940
TI - Effects of cardiopulmonary resuscitation time on chest wall compliance in
patients with cardiac arrest.
PMID- 28499933
TI - Major review: Molecular genetics of primary open-angle glaucoma.
AB - Glaucoma is a leading cause of irreversible blindness worldwide. Primary open
angle glaucoma (POAG), the most common type, is a complex inherited disorder that
is characterized by progressive retinal ganglion cell death, optic nerve head
excavation, and visual field loss. The discovery of a large, and growing, number
of genetic and chromosomal loci has been shown to contribute to POAG risk, which
carry implications for disease pathogenesis. Differential gene expression
analyses in glaucoma-affected tissues as well as animal models of POAG are
enhancing our mechanistic understanding in this common, blinding disorder. In
this review we summarize recent developments in POAG genetics and molecular
genetics research.
PMID- 28499941
TI - MTUS1, a gene encoding angiotensin-II type 2 (AT2) receptor-interacting proteins,
in health and disease, with special emphasis on its role in carcinogenesis.
AB - Loss of tumor suppressor activity is a frequent event in the formation and
progression of tumors and has been listed as an important hallmark of cancers.
Microtubule-Associated Scaffold Protein 1 (MTUS1) is a candidate tumor suppressor
gene which is reported to be frequently down-regulated in a variety of human
cancers including pancreas, colon, bladder, head-and-neck, ovarian, breast
cancers, gastric, lung cancers. It is also reported to be implicated in several
types of pathologies such as cardiac hypertrophy, atherosclerosis, and SLE-like
lymphoproliferative diseases. Moreover, MTUS1-encoded proteins are shown to be
involved in the regulation of vital cellular processes such as proliferation,
differentiation, DNA repair, inflammation, vascular remodeling and senescence.
However, the current knowledge is very limited about the role of this gene in
human cancers as well as other type diseases. Besides, there is no literature
report which summarizes and criticizes the importance of MTUS1 in the cellular
processes, especially in the processes of carcinogenesis. Accordingly, in this
comprehensive review, we tried to shed light on the role of tumor suppressor
MTUS1/ATIP in health and disease, putting special emphasis on its role in the
development and progression of human cancers as well as associated molecular
mechanisms and the reasons behind MTUS1/ATIP deficiency, which have been not well
documented previously.
PMID- 28499942
TI - Metformin ameliorates hypoxia/reoxygenation-induced cardiomyocyte apoptosis based
on the SIRT3 signaling pathway.
AB - Myocardial hypoxia/reoxygenation (H/R) injury is one of the main causes of death
and disability worldwide. However, a limited number of therapies are available to
minimize the detrimental effects of this injury. Recently, researchers have
demonstrated that metformin exerts direct cardioprotective effects against H/R.
The aim of this study was to investigate the underlying mechanisms of how
metformin affects myocardial hypoxia/reoxygenation (H/R) injury. In our study,
the activities of lactate dehydrogenase (LDH) and superoxide dismutase (SOD) as
well as the levels of malondialdehyde (MDA) were measured. Following H/R injury,
LDH activity and MDA levels were evidently increased, while SOD activity and cell
viability significantly decreased. Surprisingly, metformin downregulated the
levels of relative reactive oxygen species (ROS) and upregulated the levels of
relative SOD following H/R injury. Furthermore, metformin-treated cells exhibited
reduced cell death, which was demonstrated to be associated with increased SIRT3
expression compared to that in the control group, as evidenced by blocking of the
protective effects of metformin on cell apoptosis by the SIRT3 inhibitor
Nicotinamide (NAM). Therefore, our results demonstrate that metformin improves
cells viability following H/R, and this cardioprotective effect is partly
mediated by the SIRT3 signaling pathway.
PMID- 28499943
TI - Molecular cloning, transcriptional profiling, and subcellular localization of
signal transducer and activator of transcription 2 (STAT2) ortholog from rock
bream, Oplegnathus fasciatus.
AB - Signal transducer and activator of transcription 2 (STAT2) is a key element that
transduces signals from the cell membrane to the nucleus via the type I
interferon-signaling pathway. Although the structural and functional aspects of
STAT proteins are well studied in mammals, information on teleostean STATs is
very limited. In this study, a STAT paralog, which is highly homologous to the
STAT2 members, was identified from a commercially important fish species called
rock bream and designated as RbSTAT2. The RbSTAT2 gene was characterized at
complementary DNA (cDNA) and genomic sequence levels, and was found to possess
structural features common with its mammalian counterparts. The complete cDNA
sequence was distributed into 24 exons in the genomic sequence. The promoter
proximal region was analyzed and found to contain potential transcription factor
binding sites to regulate the transcription of RbSTAT2. Phylogenetic studies and
comparative genomic structure organization revealed the distinguishable evolution
for fish and other vertebrate STAT2 orthologs. Transcriptional quantification was
performed by SYBR Green quantitative real-time PCR (qPCR) and the ubiquitous
expression of RbSTAT2 transcripts was observed in all tissues analyzed from
healthy fish, with a remarkably high expression in blood cells. Significantly
(P<0.05) altered transcription of RbSTAT2 was detected after immune challenge
experiments with viral (rock bream irido virus; RBIV), bacterial (Edwardsiella
tarda and Streptococcus iniae), and immune stimulants (poly I:C and LPS).
Antiviral potential was further confirmed by WST-1 assay, by measuring the
viability of rock bream heart cells treated with RBIV. In addition, results of an
in vitro challenge experiment signified the influence of rock bream interleukin
10 (RbIL-10) on transcription of RbSTAT2. Subcellular localization studies by
transfection of pEGFP-N1/RbSTAT2 into rock bream heart cells revealed that the
RbSTAT2 was usually located in the cytoplasm and translocated near to the nucleus
upon poly I:C administration. Altogether, these findings suggest that RbSTAT2 is
involved in various biologically crucial mechanisms, and provides immune
protection to the rock bream.
PMID- 28499944
TI - Comparison of different coating techniques on the properties of FucoPol films.
AB - Plasma deposition, liquid flame spray (LFS) and atomic layer deposition (ALD)
were used to form inorganic coatings in new exopolysaccharide (FucoPol)
biodegradable films. Coated films were characterised in terms of surface, optical
and barrier properties in order to evaluate their potential use in food
packaging. FucoPol films presented dense and homogeneous surface with instant
water contact angle of 95. Plasma deposition of perfluorohexane (PFH) on FucoPol
surface has not shown significant improvement in the hydrophobic behaviour over
the time. The FucoPol coating of SiO2 nanoparticles deposited by LFS and plasma
deposition of PFH have shown higher instant water contact angle (135 degrees )
caused by coating surface roughness, but this hydrophobic behaviour was not
stable over time. FucoPol films coated only with TiO2 deposited by ALD and
combination of that with plasma deposition of PFH have shown stable water contact
angle during time (90 and 115, respectively), transparency in the same order of
magnitude and significantly lower permeability to water vapour (3.45*10-11mol/m s
Pa and 3.45*10-11mol/m s Pa when compared to uncoated films with 5.32*10-11mol/m
s Pa). Moreover, films coated with TiO2-PFH have also shown a permeability to
oxygen of 1.70*10-16molm/m2sPa which is 67% lower than uncoated films.
PMID- 28499945
TI - DSC investigation of bovine hide collagen at varying degrees of crosslinking and
humidities.
AB - Bovine hide collagen (nonCLC; non-CrossLinked Collagen) was analysed by
differential scanning calorimetry (DSC) at different hydration degrees and
compared with hide collagen samples crosslinked with glutaraldehyde (CLC-GA) and
chromium(III) ions (CLC-Cr), respectively. Crosslinking and drying were confirmed
to increase the denaturation temperature. Different regions were assigned, that
reflect the variation of the influence of water on the denaturation temperature.
Furthermore, at moderate hydration degrees, the enthalpies of non-crosslinked
collagen increase compared to the fully hydrated state. This reflects a glue-like
action of water in the range of 25% hydration. Crosslinking of bovine hide
collagen decreases the enthalpy by 25% in the fully hydrated state, even at very
low levels of crosslinking This can be explained by intensive effects of the
crosslinking agent on the hydration network of the collagen molecules, assuming
that the enthalpies are principally a result of hydrogen bonding. At very low
water contents DSC peaks of CLC-Cr completely disappear. This could be explained
by competition between hydroxosulfochromate(III) complexes and collagen for
water.
PMID- 28499946
TI - Lipid drug conjugate nanoparticle as a potential nanocarrier for the oral
delivery of pemetrexed diacid: Formulation design, characterization, ex vivo, and
in vivo assessment.
AB - The present work was to develop lipid drug conjugated (LDC) nanoparticles for the
potential oral delivery of pemetrexed diacid (PTX) and evaluation of its in
vitro, ex vivo and in vivo potentials. The LDC was prepared by salt formation of
PTX with stearic acid and followed by cold homogenization technique to produce
the LDC nanoparticles. FTIR analysis of LDC proved the presence of amide bond in
LDC powder indicating the conjugation between drug and lipid. LDC nanoparticles
was found to have particle size 121.9+/-1.85nm and zeta potential -51.6mV+/-1.23
and entrapment efficiency 81.0+/-0.89%. TEM images revealed spherical morphology
and were in corroboration with particle size measurements. Ex vivo gut permeation
studies revealed a very good enhancement in permeation of drug present in the LDC
as compared to plain drug solution and were confirmed by CLSM. MTT assay
conformed significant% toxicity at the end of 24h and 48h. Furthermore, the AUC0
24 of PTX from the optimized LDC nanoparticels was found to be 4.22 folds higher
than that from PTX suspension on oral administration. Thus, LDC has high
potential for the oral delivery of PTX in cancer therapy and future prospects for
the industrial purpose.
PMID- 28499947
TI - Effect of chemical denaturants on the conformational stability of GyrB subunit of
DNA gyrase from Salmonella enterica serovar Typhi.
AB - DNA gyrase, a type II topoisomerase maintains the topology of DNA by introducing
negative supercoils using energy generated by ATP hydrolysis. It is composed of
two subunits, GyrA and GyrB (GyrA2GyrB2 hetero-tetramer). GyrB comprises two
domains, a 43kDa amino N-terminus (GBNTD) and 47kDa carboxyl C- terminus (GBCTD).
Till now no study has been reported in terms of stability of Gyrase B and its
domains using chemical denaturants related to its function. To understand the
role of each domain in GyrB subunit, we estimated the thermodynamic stability of
GBF and its individual domains using urea and GdmCl. Changes in secondary and
tertiary structures were monitored using circular dichroism and fluorescence
spectroscopy. The Cm values for GBNTD, GBCTD and GBF proteins were found to be
2.25, 1.65 and 1.82M during GdmCl-induced denaturation and 2.95, 2.25 and 2.67M
for urea-induced denaturation. It is observed that GBNTD is more stable than
GBCTD and it contributes to overall stability of GyrB. The lower Cm and DeltaG
values reflect the flexibility of GBCTD to form the catalytic site along with
GANTD for cleavage or religation reaction. Both GdmCl- and urea-induced
denaturation of GyrB domains were reversible over the entire range of
concentration.
PMID- 28499948
TI - Antibacterial and wound healing properties of chitosan/poly(vinyl alcohol)/zinc
oxide beads (CS/PVA/ZnO).
AB - Treatment against bacterial infection is crucial for wound healing. Development
of cost-effective antibacterial agent with wound healing properties is still in
high demand. In this study we aimed to design chitosan/poly(vinyl alcohol)/zinc
oxide (CS/PVA/ZnO) beads as novel antibacterial agent with wound healing
properties. CS/PVA/ZnO beads were synthesized, and characterized by using XRD,
FTIR, SEM, and TEM analysis. Pure chitosan exhibits two peaks at 2theta=10 and 20
and the CS/PVA polymer matrix exhibit the peaks at 2theta=19.7 degrees and
another of low intensity at 2theta=11.5 degrees . Pure ZnO shows the
characteristic peaks at (100), (002), (101), (102), (110), (103), (200), and
(112) that were in good agreement with wurtzite ore having hexagonal lattice
structure. The antibacterial activity of CS/PVA/ZnO against Escherichia coli, and
Staphylococcus aureus were evaluated with the zone of inhibition method.
Antibacterial activity of CS/PVA/ZnO was higher than that of chitosan (CS) and
poly(vinyl alcohol (PVA). Hemocompatibility and biocompatibility of CS/PVA/ZnO
were tested in in vitro. Wound healing properties of CS/PVA/ZnO were tested in
mice skin wound. CS/PVA/ZnO showed strong antimicrobial, wound healing effect,
hemocompatibility and biocompatibility. Hence the results strongly support the
possibility of using this novel CS/PVA/ZnO material for the anti bacterial and
wound healing application.
PMID- 28499949
TI - Optimization of polysaccharides extraction from Dictyophora indusiata and
determination of its antioxidant activity.
AB - Response surface methodology (RSM) was used to optimize the extraction conditions
of polysaccharides from the fruiting body of Dictyophora indusiata (DIP). Effect
of extraction time, extraction temperature and solid to liquid ratio on the yield
of DIP was investigated. The optimum extraction conditions for DIP were as
follows: extraction time, 2.1h, solid to liquid ratio, 1:37, and extraction
temperature, 92 degrees C. Under these conditions, the experimental extraction
yield of DIP was 15.95+/-0.144%, which was matched closely to the predicted
value. During the antioxidant experiments in vitro, DIP exhibited a strong
reducing capacity and strong scavenging activity on DPPH, superoxide, and
hydroxyl radicals. The EC50 of DIP on DPPH, hydroxyl and superoxide radicals was
0.89mg/L, 0.51mg/mL and 0.68mg/mL, respectively. This suggests that
polysaccharides from D. indusiata have the potential to be the resources of
natural antioxidants.
PMID- 28499950
TI - Modifiable risk factors promoting neurodegeneration is associated with two novel
brain degradation markers measured in serum.
AB - There has been limited success with blood-based biomarkers of neurodegeneration.
One perceived reason is that blood has no direct contact to the brain. Recently
developed blood-based biomarkers of tau-degradation have shown promise as
potential tools for peripheral assessment of neurodegeneration; however, factors
contributing to the levels of these in blood are poorly understood. Using
multiple linear regression analysis in cross-sectional data from an observational
cohort (n = 5626), the aim was to examine which factors correlate to the
serological levels of two novel biomarkers measuring truncated tau fragments (Tau
A and Tau-C) in serum. Platelets, albumin and several modifiable risk factors,
including Body Mass Index, high density lipoprotein and white blood cell count
were associated with the serum level of tau fragments. The factors associated
with tau in serum may promote neurodegeneration and alter the permeability of the
Blood Brain Barrier through chronic inflammation and vascular dysfunction. These
data are of key importance for understanding the mechanism of release and
subsequent peripheral processing of tau from the brain and will assist in the
development of future blood-based biomarkers.
PMID- 28499951
TI - Effects of task-specific rehabilitation training on tau modification in rat with
photothrombotic cortical ischemic damage.
AB - Although stroke elicits progressive cognitive decline and is a leading cause of
dementia, molecular interplay between stroke and Alzheimer's disease (AD)
pathology has not been fully elucidated. Furthermore, studies on the effects of
post-stroke rehabilitation on AD pathology are limited. We evaluated the acute
effect of stroke on tau modification, and the molecular effects of task-specific
training (TST) on tau modification using a model of photochemically-induced
thrombosis (PIT)-induced cortical infarction. Following PIT in the dominant side
of sensorimotor cortex, the rehabilitation group received 4-weeks of TST
rehabilitation once daily by single pellet reaching training, whereas the
sedentary control group did not received any type of training. Cortical
expression levels of proteins related to tau modification were evaluated on post
stroke day 1 (PSD1) and 28; functional tests were also evaluated performed every
week. The expression levels of acetyl-tau, phosphorylated-tau (p-tau),
cyclooxygenase-2 and Akt-mTORC1-p70S6K pathway in infarcted cortices on PSD1 were
significantly greater, whereas the expression levels of p-AMPK were significantly
lower than in the paired contralateral sides. TST rehabilitation for 4 weeks
greatly improved functional motor performance but not memory, which concurred
with the down-regulations of ipsilateral p-AMPK, cyclooxygenase-2, Akt-mTORC1
p70S6K pathway, and p-tau in rehabilitation group. PIT-induced cortical
infarction was found to induce cortical tau modification through the Akt-mTORC1
p70S6K activation, and to suppress the expression of AMPK-related proteins. TST
rehabilitation greatly improved motor function, but not memory, and suppressed p
tau expression and neuroinflammation. Nevertheless, the role of TST-mediated
regulation of tau hyperphosphorylation required further clarification.
PMID- 28499952
TI - Data management plans: the missing perspective.
AB - The National Institutes of Health requires data sharing plans for projects with
over five hundred thousand dollars in direct costs in a single year and has
recently released a new guidance on rigor and reproducibility in grant
applications. The National Science Foundation outright requires Data Management
Plans (DMPs) as part of applications for funding. However, there is no general
and definitive list of topics that should be covered in a DMP for a research
project. We identified and reviewed DMP requirements from research funders. Forty
three DMP topics were identified. The review uncovered inconsistent requirements
for written DMPs as well as high variability in required or suggested DMP topics
among funder requirements. DMP requirements were found to emphasize post
publication data sharing rather than upstream activities that impact data
quality, provide traceability or support reproducibility. With the emphasis
equalized, the forty-three identified topics can aid Data Managers in
systematically generating comprehensive DMPs that support research project
planning and funding application evaluation as well as data management conduct
and post-publication data sharing.
PMID- 28499953
TI - Analysis and modelling of septic shock microarray data using Singular Value
Decomposition.
AB - Being a high throughput technique, enormous amounts of microarray data has been
generated and there arises a need for more efficient techniques of analysis, in
terms of speed and accuracy. Finding the differentially expressed genes based on
just fold change and p-value might not extract all the vital biological signals
that occur at a lower gene expression level. Besides this, numerous mathematical
models have been generated to predict the clinical outcome from microarray data,
while very few, if not none, aim at predicting the vital genes that are important
in a disease progression. Such models help a basic researcher narrow down and
concentrate on a promising set of genes which leads to the discovery of gene
based therapies. In this article, as a first objective, we have used the lesser
known and used Singular Value Decomposition (SVD) technique to build a microarray
data analysis tool that works with gene expression patterns and intrinsic
structure of the data in an unsupervised manner. We have re-analysed a microarray
data over the clinical course of Septic shock from Cazalis et al. (2014) and have
shown that our proposed analysis provides additional information compared to the
conventional method. As a second objective, we developed a novel mathematical
model that predicts a set of vital genes in the disease progression that works by
generating samples in the continuum between health and disease, using a simple
normal-distribution-based random number generator. We also verify that most of
the predicted genes are indeed related to septic shock.
PMID- 28499954
TI - Systematic review and meta-analysis of gait mechanics in young and older adults.
AB - BACKGROUND: Age-related gait changes may play a critical role in functional
limitations of older adults. Despite sizable interest in determining how age
alters walking mechanics, small sample sizes and varied outcome measures have
precluded a comprehensive understanding of the impact of age on lower extremity
joint kinematics and kinetics. OBJECTIVE: The aim of this study was to perform a
systematic review and meta-analysis of the aging gait mechanics literature.
METHODS: The overall standardized effect of age on walking mechanics was computed
for 29 studies (200 standardized effects). To account for variation in reported
outcome variables, analyses were carried out for comparisons between young and
older adult results using all discrete kinematic or kinetic variables reported
for the ankle, knee, or hip. Different variables reported for a given joint were
then analyzed as separate categorical moderators. RESULTS: The overall
standardized effect of age was large for ground reaction forces, moderate for
ankle and small for knee and hip kinematics and ankle and hip kinetics. When the
analysis was restricted to studies with similar or matched walking speed, the
standardized effects of age remained similar except for hip power generation and
knee kinematic variables. CONCLUSIONS: The results of this meta-analysis provide
evidence to support moderate standardized effects, with and without consideration
of walking speeds, for changes in lower extremity kinematics, joint moments and
powers at the ankle, and ground reaction forces. The standardized effects of age
for knee mechanics are less conclusive and would benefit from further research.
PMID- 28499955
TI - Transcriptomic analysis of Saccharomyces cerevisiae upon honokiol treatment.
AB - Honokiol (HNK), one of the main medicinal components in Magnolia officinalis,
possesses antimicrobial activity against a variety of pathogenic bacteria and
fungi. However, little is known of the molecular mechanisms underpinning the
antimicrobial activity. To explore the molecular mechanism of its antifungal
activity, we determined the effects of HNK on the mRNA expression profile of
Saccharomyces cerevisiae using a DNA microarray approach. HNK markedly induced
the expression of genes related to iron uptake and homeostasis. Conversely, genes
associated with respiratory electron transport were downregulated, mirroring the
effects of iron starvation. Meanwhile, HNK-induced growth deficiency was partly
rescued by iron supplementation and HNK reacted with iron, producing iron
complexes that depleted iron. These results suggest that HNK treatment induced
iron starvation. Additionally, HNK treatment resulted in the upregulation of
genes involved in protein synthesis and drug resistance networks. Furthermore,
the deletion of PDR5, a gene encoding the plasma membrane ATP binding cassette
(ABC) transporter, conferred sensitivity to HNK. Overexpression of PDR5 enhanced
resistance of WT and pdr5Delta strains to HNK. Taken together, these findings
suggest that HNK, which can be excluded by overexpression of Pdr5, functions in
multiple cellular processes in S. cerevisiae, particularly in inducing iron
starvation to inhibit cell growth.
PMID- 28499956
TI - Group X hybrid histidine kinase Chk1 is dispensable for stress adaptation, host
pathogen interactions and virulence in the opportunistic yeast Candida
guilliermondii.
AB - Hybrid histidine kinases (HHKs) progressively emerge as prominent sensing
proteins in the fungal kingdom and as ideal targets for future therapeutics. The
group X HHK is of major interest, since it was demonstrated to play an important
role in stress adaptation, host-pathogen interactions and virulence in some yeast
and mold models, and particularly Chk1, that corresponds to the sole group X HHK
in Candida albicans. In the present work, we investigated the role of Chk1 in the
low-virulence species Candida guilliermondii, in order to gain insight into
putative conservation of the role of group X HHK in opportunistic yeasts. We
demonstrated that disruption of the corresponding gene CHK1 does not influence
growth, stress tolerance, drug susceptibility, protein glycosylation or cell wall
composition in C. guilliermondii. In addition, we showed that loss of CHK1 does
not affect C. guilliermondii ability to interact with macrophages and to
stimulate cytokine production by human peripheral blood mononuclear cells.
Finally, the C. guilliermondii chk1 null mutant was found to be as virulent as
the wild-type strain in the experimental model Galleria mellonella. Taken
together, our results demonstrate that group X HHK function is not conserved in
Candida species.
PMID- 28499957
TI - Costs of outpatient parenteral antimicrobial therapy (OPAT) administered by
Hospital at Home units in Spain.
AB - The aim of this study was to assess the direct healthcare costs of outpatient
parenteral antimicrobial therapy (OPAT) administered by Hospital at Home (HaH)
units in Spain. An observational, multicentre, economic evaluation of
retrospective cohorts was conducted. Patients were treated at home by the HaH
units of three Spanish hospitals between January 2012 and December 2013. From the
cost accounting of HaH OPAT (staff, pharmacy, transportation, diagnostic tests
and structural), the cost of each outpatient course was obtained following a top
down strategy based on the use of resources. Costs associated with inpatient
stay, if any, were estimated based on length of stay and ICD-9-CM diagnosis.
There were 1324 HaH episodes in 1190 patients (median age 70 years). The median
(interquartile range) stay at home was 10 days (7-15 days). Of the OPAT episodes,
91.5% resulted in cure or improvement on completion of intravenous therapy. The
mean total cost of each infectious episode was ?6707 [95% confidence interval
(CI) ?6189-7406]. The mean cost per OPAT episode was ?1356 (95% CI ?1247-1560),
mainly distributed between healthcare staff costs (46%) and pharmacy costs (39%).
The mean cost of inpatient hospitalisation of an infectious episode was ?4357
(95% CI ?3947-4977). The cost per day of inpatient hospitalisation was ?519,
whilst the cost per day of OPAT was ?98, meaning a saving of 81%. This study
shows that OPAT administered by HaH units resulted in lower costs compared with
inpatient care in Spain.
PMID- 28499958
TI - Unexpected persistence of extended-spectrum beta-lactamase-producing
Enterobacteriaceae in the faecal microbiota of hospitalised patients treated with
imipenem.
AB - Imipenem is active against extended-spectrum beta-lactamase-producing
Enterobacteriaceae (ESBL-E) but favours the intestinal emergence of resistance.
The effects of imipenem on intestinal microbiota have been studied using culture
based techniques. In this study, the effects were investigated in patients using
culture and metagenomic techniques. Seventeen hospitalised adults receiving
imipenem were included in a multicentre study (NCT01703299,
http://www.clinicaltrials.gov). Most patients had a history of antibiotic use
and/or hospitalisation. Stools were collected before, during and after imipenem
treatment. Bacterial and fungal colonisation was assessed by culture, and
microbiota changes were assessed using metagenomics. Unexpectedly, high
colonisation rates by imipenem-susceptible ESBL-E before treatment (70.6%)
remained stable over time, suggesting that imipenem intestinal concentrations
were very low. Carriage rates of carbapenem-resistant Gram-negative bacilli (0
25.0%) were also stable over time, whereas those of yeasts (64.7% before
treatment) peaked at 76.5% during treatment and decreased thereafter. However,
these trends were not statistically significant. Yeasts included highly diverse
colonising Candida spp. Metagenomics showed no global effect of imipenem on the
bacterial taxonomic profiles at the sequencing depth used but demonstrated
specific changes in the microbiota not detected with culture, attributed to
factors other than imipenem, including sampling site or treatment with other
antibiotics. In conclusion, culture and metagenomics were highly complementary in
characterising the faecal microbiota of patients. The changes observed during
imipenem treatment were unexpectedly limited, possibly because the microbiota was
already disturbed by previous antibiotic exposure or hospitalisation.
PMID- 28499959
TI - Impact of initial empirical antifungal agents on the outcome of critically ill
patients with invasive candidiasis: analysis of the China-SCAN study.
AB - The effect of different empirical antifungal agents on the clinical outcome of
critically ill patients with invasive candidiasis (IC) has not been fully
elucidated. In this study, 136 patients with proven IC who received empirical
therapy in the China-SCAN multicentre study were retrospectively analysed.
Initial empirical antifungal monotherapy consisted of a triazole [fluconazole (n
= 61), voriconazole (n = 20) or itraconazole (n = 12)] or an echinocandin (n =
43). Hospital mortality as the primary outcome and global responses (clinical and
microbiological) were assessed. The results indicated that rates of hospital
mortality (P = 0.006) and intensive care unit (ICU) mortality (P = 0.011) were
significantly lower in patients treated with an echinocandin compared with those
receiving fluconazole, voriconazole or itraconazole. Multivariate regression
analysis indicated that the type of antifungal agent used in empirical therapy
was an independent predictor of hospital mortality (P = 0.033). Initial empirical
echinocandin treatment was associated with decreased hospital mortality compared
with fluconazole [odds ratio (OR) = 0.22, 95% confidence interval (CI) 0.06-0.85;
P = 0.028], voriconazole (OR = 0.11, 95% CI 0.02-0.56; P = 0.008) or itraconazole
(OR = 0.12, 95% CI 0.02-0.72; P = 0.020). Similar findings were observed for the
clinical success endpoint. This study demonstrated that the initial empirical
antifungal agent was an independent predictor of hospital mortality in critically
ill patients with IC. Empirical therapy with an echinocandin was associated with
decreased hospital mortality and greater clinical success than empirical therapy
with fluconazole, voriconazole or itraconazole.
PMID- 28499960
TI - Association between dipstick hematuria and decline in estimated glomerular
filtration rate among Japanese patients with type 2 diabetes: A prospective
cohort study [Diabetes Distress and Care Registry at Tenri (DDCRT 14)].
AB - AIMS: To assess the association between dipstick hematuria and estimated
glomerular filtration rate (eGFR) decline in Japanese patients with type 2
diabetes. METHODS: Longitudinal data were obtained from 3068 Japanese patients
with type 2 diabetes. To assess the independent association between dipstick
hematuria and eGFR decline, we used Cox proportional hazard model adjusted for
potential confounders. RESULTS: Median follow-up period was 699.7days. Mean age,
body mass index (BMI), and HbA1c level were 65.7years, 24.6kg/m2, and 7.5%
(58.1mmol/mol), respectively. Positive dipstick hematuria was significantly
associated with baseline eGFR and severity of albuminuria (p<0.001). The
multivariable-adjusted hazard ratio for eGFR decline in patients with dipstick
hematuria compared with those without dipstick hematuria was 2.19 [95% confidence
interval (CI): 1.22-3.91]; this association remained significant even after the
exclusion of patients who did not have diabetic retinopathy (hazard ratio: 2.39;
95% CI: 1.13-5.04). CONCLUSION: Positive dipstick hematuria was associated with
severity of albuminuria and renal function. A significant association was found
between dipstick hematuria and increased risk of eGFR decline among patients with
type 2 diabetes. Therefore, our results suggest that dipstick hematuria is
perhaps indicative of more severe diabetic nephropathy.
PMID- 28499961
TI - Towards an improved global understanding of treatment and outcomes in people with
type 2 diabetes: Rationale and methods of the DISCOVER observational study
program.
AB - AIM: Contemporary global real-world data on the management of type 2 diabetes are
scarce. The global DISCOVER study program aims to describe the disease management
patterns and a broad range of associated outcomes in patients with type 2
diabetes initiating a second-line glucose-lowering therapy in routine clinical
practice. METHODS: The DISCOVER program comprises two longitudinal observational
studies involving more than 15,000 patients in 38 countries across six
continents. Study sites have been selected to be representative of type 2
diabetes management in each country. Data will be collected at baseline
(initiation of second-line therapy), at 6months, and yearly during a 3-year
follow-up period. RESULTS: The DISCOVER program will record patient, healthcare
provider, and healthcare system characteristics, treatment patterns, and factors
influencing changes in therapy. In addition, disease control (e.g. achievement of
glycated hemoglobin target), management of associated risk factors (e.g.
hypercholesterolemia and hypertension), and healthcare resource utilization will
be recorded. Microvascular and macrovascular complications, incidence of
hypoglycemic events, and patient-reported outcomes will also be captured.
CONCLUSIONS: The DISCOVER program will provide insights into the current
management of patients with type 2 diabetes worldwide, which will contribute to
informing future clinical guidelines and improving patient care.
PMID- 28499962
TI - Diabetes and male sex are key risk factor correlates of the extent of coronary
artery calcification: A Euro-CCAD study.
AB - BACKGROUND AND AIMS: Although much has been written about the conventional
cardiovascular risk factor correlates of the extent of coronary artery
calcification (CAC), few studies have been carried out on symptomatic patients.
This paper assesses the potential ability of risk factors to associate with an
increasing CAC score. METHODS: From the European Calcific Coronary Artery Disease
(Euro-CCAD) cohort, we retrospectively investigated 6309 symptomatic patients,
62% male, from Denmark, France, Germany, Italy, Spain and the USA. All had
conventional cardiovascular risk factor assessment and CT scanning for CAC
scoring. RESULTS: Among all patients, male sex (OR = 4.85, p<0.001) and diabetes
(OR = 2.36, p<0.001) were the most important risk factors of CAC extent, with
age, hypertension, dyslipidemia and smoking also showing a relationship. Among
patients with CAC, age, diabetes, hypertension and dyslipidemia were associated
with an increasing CAC score in males and females, with diabetes being the
strongest dichotomous risk factor (p<0.001 for both). These results were echoed
in quantile regression, where diabetes was consistently the most important
correlate with CAC extent in every quantile in both males and females. To a
lesser extent, hypertension and dyslipidemia were also associated in the high CAC
quantiles and the low CAC quantiles respectively. CONCLUSION: In addition to age
and male sex in the total population, diabetes is the most important correlate of
CAC extent in both sexes.
PMID- 28499963
TI - Neither artificial light at night, anthropogenic noise nor distance from roads
are associated with oxidative status of nestlings in an urban population of
songbirds.
AB - Increasing urbanization is responsible for road-related pollutants and causes an
unprecedented increase in light and noise pollution, with potential detrimental
effects for individual animals, communities and ecosystems. These stressors
rarely act in isolation but studies dissecting the effects of these multiple
stressors are lacking. Moreover, studies on urban stressors have mainly focused
on adults, while exposure in early-life may be detrimental but is largely
ignored. To fill this important knowledge gap, we studied if artificial light at
night, anthropogenic noise and road-related pollution (using distance from roads
as a proxy) explain variation in oxidative status in great tit nestlings (Parus
major) in an urban population. Artificial light at night, anthropogenic noise and
distance from roads were not associated with variation of the nine studied
metrics of oxidative status (superoxide dismutase-SOD-, glutathione peroxidase
GPX, catalase-CAT-, non-enzymatic total antioxidant capacity-TAC-, reduced
glutathione-GSH-, oxidized glutathione-GSSG-, ratio GSH/GSSG, protein carbonyls
and thiobarbituric acid reactive substances-TBARS). Interestingly, for all
oxidative status metrics, we found that there was more variation in oxidative
status among individuals of the same nest compared to between different nests. We
also showed an increase in protein carbonyls and a decrease of the ratio GSH/GSSG
as the day advanced, and an increase of GPX when weather conditions deteriorated.
Our study suggests that anthropogenic noise, artificial light at night and road
related pollution are not the most important sources of variation in oxidative
status in great tit nestlings. It also highlights the importance of considering
bleeding time and weather conditions in studies with free-living animals.
PMID- 28499964
TI - Life-history dependent relationships between body condition and immunity, between
immunity indices in male Eurasian tree sparrows.
AB - In free-living animals, recent evidence indicates that innate, and acquired,
immunity varies with annual variation in the demand for, and availability of,
food resources. However, little is known about how animals adjust the
relationships between immunity and body condition, and between innate and
acquired immunity to optimize survival over winter and reproductive success
during the breeding stage. Here, we measured indices of body condition (size
corrected mass [SCM], and hematocrit [Hct]), constitutive innate immunity (plasma
total complement hemolysis activity [CH50]) and acquired immunity (plasma
immunoglobulin A [IgA]), plus heterophil/lymphocyte (H/L) ratios, in male
Eurasian tree sparrows (Passer montanus) during the wintering and the breeding
stages. We found that birds during the wintering stage had higher IgA levels than
those from the breeding stage. Two indices of body condition were both negatively
correlated with plasma CH50 activities, and positively with IgA levels in
wintering birds, but this was not the case in the breeding birds. However, there
was no correlation between CH50 activities and IgA levels in both stages. These
results suggest that the relationships between body condition and immunity can
vary across life-history stage, and there are no correlations between innate and
acquired immunity independent of life-history stage, in male Eurasian tree
sparrows. Therefore, body condition indices predict immunological state,
especially during the non-breeding stage, which can be useful indicators of
individual immunocompetences for understanding the variations in innate and
acquired immunity in free-living animals.
PMID- 28499965
TI - Effects of dietary dandelion extracts on growth performance, body composition,
plasma biochemical parameters, immune responses and disease resistance of
juvenile golden pompano Trachinotus ovatus.
AB - The present study was conducted to investigate the effects of dietary dandelion
extracts (DE) supplementation on growth performance, feed utilization, body
composition, plasma biochemical indices, immune responses, hepatic antioxidant
abilities, and resistance to the pathogen Vibrio harveyi in Trachinotus ovatus. A
basal diet supplemented with DE at 0, 0.50, 1.00, 2.00, 4.00 and 10.00 g kg-1
were fed to golden pompano for 8 weeks. The study indicated that dietary
supplementation with DE could significantly improve final body weight (FBW),
weight gain rate (WGR), specific growth rate (SGR), feed efficiency ratio (FER),
feed intake (FI), protein efficiency ratio (PER) and protein deposit rate (PDR)
(P < 0.05). The highest FBW, WGR, SGR, FI and PDR were observed in fish fed 1.00
g kg-1 dietary DE (P < 0.05). The highest FER and PER were recorded at 0.50 g kg
1 dietary DE (P < 0.05). Condition factor, viscerosomatic index, hepatosomatic
index and survival were not significantly different among all groups. Fish fed
1.00 g kg-1 dietary DE showed significant increase in plasma total protein,
complement 4 content and alkaline phosphatase, lysozyme, glutathione reductase
(GSR) activity, but significant decrease in triglyceride, low density lipoprotein
cholesterol, malondialdehyde (MDA) content and aspartate aminotransferase
activities compared to the control group (P < 0.05). Hepatic antioxidant enzymes
(SOD, T-AOC, CAT, GSH-Px, GSR) significantly increased whereas MDA content
significantly decreased in fish fed 1.00 g kg-1 DE supplement (P < 0.05). After
challenge with Vibrio harveyi, significant higher post-challenge survival was
observed in fish fed DE supplement (P < 0.05). These results indicated that
golden pompano fed a diet supplemented with DE (especially at 1.00 g kg-1 of fed
supplement) could significantly promote its growth performance, feed utilization,
body protein deposit, immune ability, hepatic and plasma antioxidative enzyme
activities and improve its resistance to infection by Vibrio harveyi.
PMID- 28499966
TI - Interferon-induced protein 56 (IFI56) is induced by VHSV infection but not by
bacterial infection in olive flounder (Paralichthys olivaceus).
AB - Interferon-inducible protein 56 (IFI56, also known as ISG56/IFIT1, interferon
induced protein with tetratricopeptide repeats 1) is strongly induced in response
to interferon and a potent inhibitor of viral replication and translational
initiation. Here, we describe the identification of IFI56 (OfIFI56) in olive
flounder, its characteristic features, and expression levels in various tissues
before and after viral hemorrhagic septicemia virus (VHSV) infection. The full
length OfIFI56 sequence was identified from rapid amplification of cDNA ends PCR.
The complete coding sequence of OfIFI56 is 1971 bp in length and encodes 431
amino acids. The putative OfIFI56 protein has multiple tetratricopeptide (TPR)
motifs, which regulate diverse biological processes, such as organelle targeting,
protein import, and vesicle fusion. Based on sequence analysis, the Larimichthys
crocea IFI56 protein (61%) had the highest sequence homology to OfIFI56. In
healthy olive flounder, OfIFI56 mRNA expression was detected in many tissues such
as intestine, gill, head kidney, heart, spleen, and trunk kidney tissues. After
VHSV challenge, OfIFI56 mRNA was significantly up-regulated in these tissues.
Additionally, OfIFI56 expression was induced by poly I:C but not by Streptococcus
parauberis and S. iniae infection or lipopolysaccharide injection in kidney and
spleen tissues of olive flounder. These results demonstrate that piscine OfIFI56
expression is not induced by bacterial infection but is selectively induced by
viral infection, especially VHSV, and that OfIFI56 may play an important role in
the host response against VHSV infection.
PMID- 28499967
TI - Molecular cloning, expression and antioxidative activity of 2-cys-peroxiredoxin
from freshwater mussel Cristaria plicata.
AB - Peroxiredoxins (Prxs) play an important role against various oxidative stresses
by catalyzing the reduction of hydrogen peroxide (H2O2) and organic
hydroperoxides to less harmful form. A 2-cys peroxiredoxin, designated as CpPrx,
was cloned from hemocytes of freshwater mussel Cristaria plicata. The full length
cDNA of CpPrx is 1247 bp, which includes an open reading frame (ORF) of 591bp,
encoding 196 amino acids. CpPrx possesses two conserved cysteine residues (Cys49,
Cys170). The deduced amino acid sequence of CpPrx showed a high level (67-74%) of
sequence similarity to 2-Cys Prxs from other species. The results of real-time
quantitative PCR revealed that CpPrx mRNA was constitutively expressed in
tissues, and the highest expression levels were in hepatopancreas and gills.
After peptidoglycan (PGN) and Aeromonas hydrophila challenge, the expression
levels of CpPrx mRNA were up-regulated in hemocytes and hepatopancreas. The cDNA
of CpPrx was cloned into the plasmid pET-32, and the recombinant protein was
expressed in Escherichia coli BL21(DE3). Comparison with DE3-pET-32 and DE3
strain, the cells of DE3-pET-32-CpPrx exhibited resistance to the concentration
of 0.4, 0.8 and 1.2 mmoL/L H2O2 in vivo.
PMID- 28499968
TI - Normal behavioral responses to light and darkness and the pupillary light reflex
are dependent upon the olivary pretectal nucleus in the diurnal Nile grass rat.
AB - The olivary pretectal nucleus (OPT) is a midbrain structure that receives
reciprocal bilateral retinal projections, is involved in the pupillary light
reflex, and connects reciprocally with the intergeniculate leaflet (IGL), a
retinorecipient brain region that mediates behavioral responses to light pulses
(i.e., masking) in diurnal Nile grass rats. Here, we lesioned the OPT and
evaluated behavioral responses in grass rats to various lighting conditions, as
well as their anxiety-like responses to light exposure. While control grass rats
remained diurnal, grass rats with OPT lesions exhibited a more night-active
pattern under 12h:12h light-dark (LD) conditions. However, when placed in
constant darkness, OPT-lesioned grass rats became more active during their
subjective day, suggesting that an exaggerated masking response to light may be
responsible for the effect of OPT lesions on locomotor activity in LD. To test
this hypothesis, we presented dark and light pulses to controls and grass rats
with OPT lesions; controls increased their activity in response to light, whereas
those with OPT lesions significantly increased activity in response to darkness.
Further, when placed in a 7-h ultradian LD cycle, animals with OPT lesions were
more active during darkness than controls. OPT lesions also abolished the
pupillary light reflex, but did not affect anxiety-like behaviors. Finally, in
animals with OPT lesions, light did not induce Fos expression in the
ventrolateral geniculate nucleus, as it did in controls. Altogether, these
results suggest that masking responses to light and darkness are dependent upon
nuclei within the subcortical visual shell in grass rats.
PMID- 28499969
TI - Corticotropin-releasing hormone modulates airway vagal preganglionic neurons of
Sprague-Dawley rats at multiple synaptic sites via activation of its type 1
receptors: Implications for stress-associated airway vagal excitation.
AB - Corticotropin-releasing hormone release is the final common pathway of stress
associated neuroendocrine responses. This study tested how corticotropin
releasing hormone modulates airway vagal preganglionic neurons. Airway vagal
preganglionic neurons in neonatal rats were retrogradely labeled with fluorescent
dye and identified in medullary slices, and their responses to corticotropin
releasing hormone (200nmolL-1) were examined using whole-cell patch clamp. The
results show that under current clamp, corticotropin-releasing hormone (200nmolL
1) depolarized airway vagal preganglionic neurons and significantly increased the
rate of their spontaneous firing. Under voltage clamp, corticotropin-releasing
hormone caused a tonic inward current and significantly facilitated the
spontaneous glutamatergic and GABAergic inputs of these neurons. Corticotropin
releasing hormone had no impact on the spontaneous glycinergic inputs of these
neurons. In the preexistence of tetrodotoxin (1MUmolL-1), corticotropin-releasing
hormone had no impact on the miniature excitatory or inhibitory postsynaptic
currents, but still induced a tonic inward current and significantly increased
the input resistance. The responses induced by corticotropin-releasing hormone
were prevented by Antalarmin hydrochloride (50MUmolL-1), an antagonist of type 1
corticotropin-releasing hormone receptors, but insensitive to Astressin 2B
(200nmolL-1), an antagonist of type 2 corticotropin-releasing hormone receptors.
These results suggest that corticotropin-releasing hormone excites airway vagal
preganglionic neurons via activation of its type 1 receptors at multiple sites,
which includes a direct postsynaptic excitatory action and presynaptic
facilitation of both glutamatergic and GABAergic inputs. In stress, corticotropin
releasing hormone might be able to activate the airway vagal nerves and,
consequently, participate in induction or exacerbation of airway disorders.
PMID- 28499970
TI - Chitinase1 contributed to a potential protection via microglia polarization and
Abeta oligomer reduction in D-galactose and aluminum-induced rat model with
cognitive impairments.
AB - Chitinase activity is increased in Alzheimer's disease (AD). However, the role of
chitinase1 in AD is unknown. We investigated the effects of chitinase1 on
Alzheimer's pathology and microglia function. Artificial chitinase1 and chitinase
inhibitor (chitinase-IN-2) were used to determine the effects of chitinase1 on
inflammatory factors and beta-amyloid (Abeta) oligomers deposition in D
galactose/AlCl3-induced rat model with cognitive impairments. Abeta-treated N9
microglia cells were analyzed to further verify whether the changes in
inflammatory factors following chitinase1 treatment were associated with
microglia alternative activation. Our data displayed that the activity of
chitinase1 was both improved in D-galactose/AlCl3-injected rats and Abeta
pretreated microglia. Moreover, there was an improvement in cognitive function in
chitinase1-treated AD rats. Furthermore, anti-inflammation factors (Arginase 1,
Arg-1, mannose receptor type C 1, MRC1/CD206) were increased and pro-inflammation
factors (tumor necrosis factor alpha, TNFalpha, interleukin 1 beta, IL-1beta)
were decreased in D-galactose/AlCl3-induced AD rats with chitinase1 treatment. A
higher level of M2 markers (Arg-1, MRC1/CD206) and a lower level of classic M1
markers (TNFa, IL-1beta) were obtained in Abeta-pretreated N9 cells with
chitinase1, suggesting that chitinase1 polarized the microglia into an anti-AD M2
phenotype. We also detected that chitnase1 could weaken the deposition of Abeta
oligomers in the brain of D-galactose/ AlCl3-induced AD rats. In conclusion,
Chitinase1 might exert protective effects against AD by polarizing microglia to
an M2 phenotype and resisting Abeta oligomer deposition.
PMID- 28499971
TI - Selective reward affects the rate of saccade adaptation.
AB - In this study we tested whether a selective reward could affect the adaptation of
saccadic eye movements in monkeys. We induced the adaptation of saccades by
displacing the target of a horizontal saccade vertically as the eye moved toward
it, thereby creating an apparent vertical dysmetria. The repeated upward target
displacement caused the originally horizontal saccade to gradually deviate upward
over the course of several hundred trials. We induced this directional adaptation
in both right- and leftward saccades in every experiment (n=20). In half of the
experiments (n=10), we rewarded monkeys only when they made leftward saccades and
in the other half (n=10) only for rightward saccades. The reaction time of
saccades in the rewarded direction was shorter and we, like others, interpreted
this change as a sign of the reward's preferential effect in that direction.
Saccades in the rewarded direction showed more rapid adaptation of their
directions than did saccades in the non-rewarded direction, indicating that the
selective reward increased the speed of saccade adaptation. The differences in
adaptation speed were reflected in changes in saccade metrics, which were usually
more noticeable in the deceleration phases of saccades than in their acceleration
phases. Because previous studies have shown that the oculomotor cerebellum is
involved with saccade deceleration and also participates in saccade adaptation,
it is possible that selective reward could influence cerebellar plasticity.
PMID- 28499972
TI - Simvastatin ameliorates memory impairment and neurotoxicity in streptozotocin
induced diabetic mice.
AB - Diabetes comes with an additional burden of moderate to severe hyperlipidemia,
but little is known about the effects of lipid-lowering therapy on diabetic
complications such as diabetes-associated cognitive decline. Herein we
investigated the effects of statins on memory impairment and neurotoxicity in
streptozotocin-induced diabetic mice. Our data indicated that oral administration
of simvastatin at 10 or 20mg/kg for 4weeks significantly ameliorated diabetes
associated memory impairment reflected by performance better in the Morris water
maze and Y-maze tests. The further study showed that these treatments caused
significant increase of peroxisome proliferator-activated receptors gamma and
decrease of NF-kappaB p65 in nucleus of hippocampus and cortex, and ameliorated
neuroinflammatory response as evidenced by less Iba-1-positive cells and lower
inflammatory mediators including IL-1beta, IL-6 and TNF-alpha as well as
suppressed neuronal apoptosis as indicated by decreased TUNEL-positive cells,
increased ratio of Bcl-2/Bax and decreased caspase-3 activity in the hippocampus
and cortex. Moreover, simvastatin pronouncedly attenuated amyloidogenesis by
decreasing amyloid-beta, amyloid precursor protein (APP) and beta-site APP
cleaving enzyme-1. As expected, treated with simvastatin, the diabetic mice
exhibited significant improvement of hyperlipidemia rather than hyperglycemia.
Our findings disclosed novel therapeutic potential of simvastatin for the
diabetes-associated cognitive impairment.
PMID- 28499973
TI - Activation of dopamine D1 receptors enhances the temporal summation and
excitability of rat retinal ganglion cells.
AB - Dopamine (DA), an important neurotransmitter and neuromodulator, plays important
roles in neuronal physiological functions by activating G-protein-coupled DA D1
and/or D2 receptors. Previous studies have demonstrated that D1 receptors are
functionally expressed in retinal neurons and glial cells, including ganglion
cells. In this study, we explored the effects of D1 receptor activation on
retinal ganglion cell (RGC) temporal summation and excitability in rat retinal
slices using electrophysiological techniques. Bath application of the selective
D1 receptor agonist SKF81297 increased the ratio of excitatory postsynaptic
potentials (EPSPs) (EPSP5/EPSP1) within an EPSP train evoked by a train
stimulation (five current pulses at 40Hz), which was blocked by co-application of
SCH23390, a specific D1 receptor antagonist. Ba2+, an inwardly rectifying K+
channel (Kir) blocker, significantly suppressed the SKF81297-induced effect,
whereas ZD7288, a specific hyperpolarization-activated cation current (Ih)
blocker, showed a moderate inhibitory effect. The cAMP/protein kinase A (PKA)
signaling pathway, but not phosphoinositide-specific phospholipase C (PI-PLC),
mediated the SKF81297-induced modulation of EPSP temporal summation. Further
experiments showed that SKF81297 suppressed Ba2+-sensitive Kir currents in RGCs.
Additionally, SKF81297 increased the spontaneous firing frequency of RGCs, and
caused depolarization of the cells with or without the presence of synaptic
receptor blockers. In contrast, SKF81297 did not significantly change the
frequency of miniature excitatory postsynaptic currents (mEPSCs) recorded in
RGCs. Our results indicate that D1 receptor activation enhances the temporal
summation of RGCs mainly by suppressing Kir currents through the cAMP/PKA
signaling pathway, thus increasing the excitability of rat RGCs.
PMID- 28499974
TI - Prefrontal cortical glutathione-dependent defense and proinflammatory mediators
in chronically isolated rats: Modulation by fluoxetine or clozapine.
AB - Chronic psychosocial stress modulates brain antioxidant systems and causes
neuroinflammation that plays a role in the pathophysiology of depression.
Although the antidepressant fluoxetine (FLX) represents the first-line treatment
for depression and the atypical antipsychotic clozapine (CLZ) is considered as a
second-line treatment for psychotic disorders, the downstream mechanisms of
action of these treatments, beyond serotonergic or dopaminergic signaling, remain
elusive. We examined behavioral changes, glutathione (GSH)-dependent defense and
levels of proinflammatory mediators in the prefrontal cortex (PFC) of adult male
Wistar rats exposed to 21days of chronic social isolation (CSIS). We also tested
the ability of FLX (15mg/kg/day) or CLZ (20mg/kg/day), applied during CSIS, to
prevent stress-induced changes. CSIS caused depressive- and anxiety-like
behaviors, compromised GSH-dependent defense, and induced nuclear factor-kappa B
(NF-kappaB) activation with a concomitant increase in cytosolic levels of
proinflammatory mediators cyclooxigenase-2, interleukin-1beta and tumor necrosis
factor-alpha in the PFC. NF-kappaB activation and proinflammatory response in the
PFC were not found in CSIS rats treated with FLX or CLZ. In contrast, only FLX
preserved GSH content in CSIS rats. CLZ not only failed to protect against CSIS
induced GSH depletion, but it diminished its levels when applied to non-stressed
rats. In conclusion, prefrontal cortical GSH depletion and the proinflammatory
response underlying depressive- and anxiety-like states induced by CSIS were
prevented by FLX. The protective effect of CLZ, which was equally effective as
FLX on the behavioral level, was limited to proinflammatory components. Hence,
different mechanisms underlie the protective effects of these two drugs in CSIS
rats.
PMID- 28499975
TI - Intracortical signal processing of periodontal ligament sensations in rat.
AB - The somatosensory information from the orofacial region, including the
periodontal ligament (PDL), is processed in a manner that differs from that used
for other body somatosensory information in the related cortices. It was reported
that electrical stimulation to rat PDL elicited activation of the insular oral
region (IOR) and the primary (S1) and secondary (S2) somatosensory cortices.
However, the physiological relationship between S1 and S2/IOR is not well
understood. To address this issue, we performed in vivo optical imaging using a
voltage-sensitive dye. Our results demonstrated that the electrical stimulation
to the PDL of the mandibular incisor evoked the simultaneous activation of S1 and
the S2/IOR. The stimulation to the initial response area of the S1 evoked
responses in the S2/IOR, and vice versa. An injection of tetrodotoxin (TTX) to
the cortical region between S1 and S2/IOR attenuated such elicited responses only
in the non-stimulated cortical partner site. The cortico-cortical interaction
between S1 and S2/IOR was suppressed by the application of TTX, indicating that
these two cortical regions bi-directionally communicate the signal processing of
PDL sensations. An injection of FluoroGoldTM (FG) to the initial response area in
S1 or the S2/IOR showed that FG-positive cells were scattered in the non-injected
cortical counterpart. This morphological result demonstrated the presence of a bi
directional intracortical connection between the initial response areas in S1 and
the S2/IOR. These findings suggest the presence of a mutual connection between S1
and the S2/IOR as an intracortical signal processing network for orofacial
nociception.
PMID- 28499976
TI - Daily modulation of the speed-accuracy trade-off.
AB - Goal-oriented arm movements are characterized by a balance between speed and
accuracy. The relation between speed and accuracy has been formalized by Fitts'
law and predicts a linear increase in movement duration with task constraints. Up
to now this relation has been investigated on a short-time scale only, that is
during a single experimental session, although chronobiological studies report
that the motor system is shaped by circadian rhythms. Here, we examine whether
the speed-accuracy trade-off could vary during the day. Healthy adults carried
out arm-pointing movements as accurately and fast as possible toward targets of
different sizes at various hours of the day, and variations in Fitts' law
parameters were scrutinized. To investigate whether the potential modulation of
the speed-accuracy trade-off has peripheral and/or central origins, a motor
imagery paradigm was used as well. Results indicated a daily (circadian-like)
variation for the durations of both executed and mentally simulated movements, in
strictly controlled accuracy conditions. While Fitts' law was held for the whole
sessions of the day, the slope of the relation between movement duration and task
difficulty expressed a clear modulation, with the lowest values in the afternoon.
This variation of the speed-accuracy trade-off in executed and mental movements
suggests that, beyond execution parameters, motor planning mechanisms are
modulated during the day. Daily update of forward models is discussed as a
potential mechanism.
PMID- 28499977
TI - Human neural stem/progenitor cells derived from the olfactory epithelium express
the TrkB receptor and migrate in response to BDNF.
AB - Neurogenesis constitutively occurs in the olfactory epithelium of mammals,
including humans. The fact that new neurons in the adult olfactory epithelium
derive from resident neural stem/progenitor cells suggests a potential use for
these cells in studies of neural diseases, as well as in neuronal cell
replacement therapies. In this regard, some studies have proposed that the human
olfactory epithelium is a source of neural stem/progenitor cells for autologous
transplantation. Although these potential applications are interesting, it is
important to understand the cell biology and/or whether human neural
stem/progenitor cells in the olfactory epithelium sense external signals, such as
brain-derived neurotrophic factor (BDNF), that is also found in other pro
neurogenic microenvironments. BDNF plays a key role in several biological
processes, including cell migration. Thus, we characterized human neural
stem/progenitor cells derived from the olfactory epithelium (hNS/PCs-OE) and
studied their in vitro migratory response to BDNF. In the present study, we
determined that hNS/PCs-OE express the protein markers Nestin, Sox2, Ki67 and
betaIII-tubulin. Moreover, the doubling time of hNS/PCs-OE was approximately 38h.
Additionally, we found that hNS/PCs-OE express the BDNF receptor TrkB, and
pharmacological approaches showed that the BDNF-induced (40ng/ml) migration of
differentiated hNS/PCs-OE was affected by the compound K252a, which prevents TrkB
activation. This observation was accompanied by changes in the number of vinculin
adhesion contacts. Our results suggest that hNS/PCs-OE exhibit a migratory
response to BDNF, accompanied by the turnover of adhesion contacts.
PMID- 28499978
TI - Salt Taste Recognition in a Heart Failure Cohort.
AB - BACKGROUND: Heart failure (HF) disproportionately affects older adults. Dietary
sodium indiscretion is frequently implicated in HF decompensation. The affinity
for and ability to taste salt in this process is unexplored. We sought to
evaluate differences in salt taste by age and HF diagnosis and to map changes
after hospitalization for acute decompensated heart failure (ADHF). METHODS:
Seventy-two subjects underwent initial salt-taste testing during hospitalization
for ADHF. Follow-up taste testing occurred at discharge and 1, 4, and 12 weeks
after hospitalization. Three different groups were included as control subjects
and underwent 1-time salt-taste testing: 10 patients with stable HF, 10 healthy
older adults, and 10 healthy younger adults. Salt-taste testing was completed
with the use of commercially available and validated Salsave test strips with
increasing concentrations of NaCl (0.6-1.6 mg/cm2) to identify salt taste
recognition threshold. Respectively, 2-sample t tests, multiple regression, and
linear mixed-effects modeling were used for intergroup comparisons, to adjust for
confounders, and to assess the effect of time after discharge from ADHF
hospitalization. RESULTS: The baseline salt taste recognition threshold was
lowest in the young healthy control group (0.62 [SD 0.05] mg/cm2 NaCl) compared
with the healthy older control subjects (0.92 [SD 0.29] mg/cm2 NaCl), stable HF
outpatients, (1.06 [SD 0.22] mg/cm2 NaCl), and ADHF subjects on admission (1.06
[SD 0.48] mg/cm2 NaCl). There was a strong trend toward higher recognition
threshold in HF patients (P = .051) that was independent from age and other
potential confounders. Serial salt-taste testing in the ADHF group demonstrated a
decrease in recognition threshold that persisted over the 12 weeks after
discharge (1.04 [SD 0.44] to 0.76 [SD 0.22] mg/cm2 NaCl; P = .003). DISCUSSION:
When compared with young healthy control subjects, HF patients have impaired
recognition of salt taste. The salt taste recognition threshold decreases after
hospitalization for ADHF. This change demonstrates the first evidence of the
phenomenon known as the "hedonic shift" in HF, in which the threshold to
recognize salt taste decreases after prescribed sodium restriction.
PMID- 28499979
TI - Inspiratory Muscle Training Improves Intercostal and Forearm Muscle Oxygenation
in Patients With Chronic Heart Failure: Evidence of the Origin of the Respiratory
Metaboreflex.
AB - BACKGROUND: The impact of inspiratory muscle training (IMT) on respiratory and
peripheral muscle oxygenation and perfusion during inspiratory muscle fatigue in
patients with chronic heart failure (HF) has not been established. METHODS AND
RESULTS: Twenty-six patients with chronic HF were randomly assigned to either 8
weeks of IMT or a control group. Inspiratory fatigue was induced by means of a
progressive inspiratory resistive loading protocol until there was an inability
to sustain inspiratory pressure, when the inspiratory muscle metaboreflex should
be activated. The main outcomes were intercostal and forearm muscle oxygen
saturation and deoxygenation as measured by means of near-infrared spectroscopy
(NIRS) and blood lactate levels. Inspiratory muscle strength was increased by 78%
(P <.001) after 8 weeks of participation in the IMT group. IMT attenuated the
reduction of oxygen saturation in intercostal and forearm muscles and the
increase in blood lactate during respiratory fatigue (P <.001 and P <.05,
respectively). These changes were different from the control group (P <.01, P
<.05, and P <.05, respectively). After 8 weeks, similar increases in oxygen
consumption, mean arterial pressure, heart rate, stroke volume, and cardiac
output were observed in both groups during respiratory fatigue. CONCLUSIONS: This
randomized controlled clinical trial demonstrates that IMT attenuates the
respiratory muscle oxygen demand-delivery mismatch during respiratory fatigue in
patients with chronic HF.
PMID- 28499980
TI - Morphological and molecular identification of Sarcocystis arctica sarcocysts in
three red foxes (Vulpes vulpes) from the Czech Republic.
AB - Muscular sarcocystosis by Sarcocystis arctica was found for the first time in the
Czech Republic, in different muscles of red fox (Vulpes vulpes). Cysts were slim,
elongated, thread-like, whitish, 1-7mm long, and 206-270MUm wide; bradyzoites
were 7.9*2.7MUm in unstained wet mounts and 9.2*2.9MUm in cyst Giemsa-stained
smears. The cyst wall was thin, with short villi-like protrusions, and no host
response was observed in the histological sections. Examination of the
distribution and intensity of sarcocysts in 17 different muscle groups revealed
that the highest intensity was in the cranial tibial muscle (>15 cysts in
compressoria), followed by the diaphragm, forearm, and other groups (with
intensities of 3-15 cysts in compressoria). Sarcocysts were detected in 3 out of
86 foxes. Genetic characterization at 18S rRNA, 28S rRNA, ITS1 and cox1,
consistently showed that the species was identical with S. arctica.
Interestingly, this protozoan was also detected as a co-infection in 3 foxes with
the nematode Trichinella spp. for the first time.
PMID- 28499981
TI - Mitochondrial dysfunction in ocular disease: Focus on glaucoma.
AB - Mitochondrial dysfunction commonly presents with ocular findings as a part of a
systemic disorder. These ophthalmic manifestations can be the first sign of a
mitochondrial abnormality, which highlights the key role of a comprehensive
ophthalmic assessment. On the other hand, a number of visually disabling genetic
and acquired eye diseases with no curative treatment show abnormal mitochondrial
function. Recent advances in mitochondrial research have improved our
understanding of previously unexplained ocular disorders utilising better
diagnostic approaches. Further studies on mitochondrial dysfunction and novel
modalities of treatment will help to improve outcomes of these conditions. In
this review article we discuss the clinical picture of common mitochondrial
related eye diseases, diagnostic approaches and possible treatment options
including a very recent interesting report about gene therapy, with a particular
focus on glaucoma.
PMID- 28499982
TI - Identification of FASTKD2 compound heterozygous mutations as the underlying cause
of autosomal recessive MELAS-like syndrome.
AB - Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes
(MELAS) is a condition that affects many parts of the body, particularly the
brain and muscles. This study examined a Korean MELAS-like syndrome patient with
seizure, stroke-like episode, and optic atrophy. Target sequencing of whole mtDNA
and 73 nuclear genes identified compound heterozygous mutations p.R205X and
p.L255P in the FASTKD2. Each of his unaffected parents has one of the two
mutations, and both mutations were not found in 302 controls. FASTKD2 encodes a
FAS-activated serine-threonine (FAST) kinase domain 2 which locates in the
mitochondrial inner compartment. A FASTKD2 nonsense mutation was once reported as
the cause of a recessive infantile mitochondrial encephalomyopathy. The present
case showed relatively mild symptoms with a late onset age, compared to a
previous patient with FASTKD2 mutation, implicating an inter-allelic clinical
heterogeneity. Because this study is the second report of an autosomal recessive
mitochondrial encephalomyopathy patient with a FASTKD2 mutation, it will extend
the phenotypic spectrum of the FASTKD2 mutation.
PMID- 28499983
TI - Photostimulation of mitochondria as a treatment for retinal neurodegeneration.
AB - Absorption of photon energy by neuronal mitochondria leads to numerous downstream
neuroprotective effects. Red and near infrared (NIR) light are associated with
significantly less safety concerns than light of shorter wavelengths and they are
therefore, the optimal choice for irradiating the retina. Potent neuroprotective
effects have been demonstrated in various models of retinal damage, by red/NIR
light, with limited data from human studies showing its ability to improve visual
function. Improved neuronal mitochondrial function, increased blood flow to
neural tissue, upregulation of cell survival mediators and restoration of normal
microglial function have all been proposed as potential underlying mechanisms of
red/NIR light.
PMID- 28499984
TI - Systemic PTEN-Akt1-mTOR pathway activity in patients with normal tension glaucoma
and ocular hypertension: A case series.
AB - Glaucoma is the most common optic neuropathy in humans and the leading cause of
irreversible blindness worldwide. Its prevalence and incidence increase
exponentially with ageing and raised intraocular pressure (IOP), while increasing
evidence suggests that systemic mitochondrial abnormalities may also be
implicated in its pathogenesis. We have recently shown that patients who have not
developed glaucoma despite being exposed for many years to high IOP (ocular
hypertension - OHT) have more efficient mitochondria, measured in peripheral
blood lymphocytes, when compared to age-similar controls and fast progressing
normal tension glaucoma (NTG) patients. In this prospective case series we aimed
to explore some of the molecular pathways involved in mitochondrial efficiency in
glaucoma resistance by measuring the systemic activity (in peripheral blood) of
key mitochondrial regulators: the mammalian target of rapamycin (mTOR) and its
major upstream regulators and downstream effectors that form the PTEN-Akt1-mTOR
signalling pathway. We found no statistically significant difference in the
systemic mTOR activity between the three groups (control, NTG and OHT). In line
with the mTOR results, there was no significant difference in the activity of
both the two major upstream mTOR regulators (PTEN and Akt1) and its two main
downstream effectors (S6K and 4EBP1). In a single NTG patient, with history of
Raynaud's, significantly higher mTOR activity was noted. We conclude that the
PTEN-Akt1-mTOR pathway does not appear to play a central role in mitochondrial
efficiency in OHT.
PMID- 28499985
TI - Functional miR-146a, miR-149, miR-196a2 and miR-499 polymorphisms and the
susceptibility to hepatocellular carcinoma: An updated meta-analysis.
AB - OBJECTIVE: Single nucleotide polymorphisms of miRNAs play important roles in the
pathogenesis of hepatocellular carcinoma (HCC). To evaluate the association
between four common miRNAs (miR-146a rs2910164; miR-149 rs2292832; miR-196a2
rs11614913 and miR-499 rs3746444) and HCC risk, an updated meta-analysis was
performed. METHODS: 32 studies including 12,405 HCC cases and 15,056 controls
were used for this meta-analysis. There were 22 studies with 7894 cases and
10,221 controls for miR-146a, 9 studies with 2684 HCC cases and 3464 controls for
miR-149, 17 studies with 6937 cases and 8217 controls for miR-196a2 and 16
studies with 4158 cases and 5264 controls for miR-499. Odds radios (ORs) and 95%
confidence intervals (CIs) were used to assess the HCC risk. RESULTS: Meta
analysis showed that miR-146a was associated with HCC risk under the heterozygote
model (OR=1.10, 95%CI=1.03-1.17, P=0.007), whereas no association was found in
Caucasian using all genetic models. For miR-196a2 polymorphism, an increased risk
of HCC was observed based on four models (C vs T: OR=1.15, 95%CI=1.05-1.26,
P=0.003; CC vs TT: OR=1.35, 95%CI=1.12-1.63, P=0.002; CC+CT vs TT: OR=1.20,
95%CI=1.04-1.37, P=0.01 and CC vs CT+TT: OR=1.23, 95%CI=1.06-1.42, P=0.006).
Association of miR-499 with HCC risk was only detected in the subgroup of studies
which did not use polymerase chain reaction and restriction fragment length
polymorphism (PCR-RFLP) under the allelic, heterozygote and dominant models.
However, negative results were obtained for the association of miR-149 and HCC
susceptibility. CONCLUSION: Our results suggest that miR-146a and miR-196a2
polymorphisms are associated with increased risk of HCC, especially in Asian.
PMID- 28499986
TI - N-acetylcysteine treatment attenuates the cognitive impairment and synaptic
plasticity loss induced by streptozotocin.
AB - Alzheimer's disease (AD) is a neurodegenerative disorder pathologically
characterized by severe neuronal and glial structural changes and progressive
cognitive decline. N-acetylcysteine (NAC) is a well-known pharmacological agent
with pro-neurogenic properties and neuroprotective effects. In this study, we
evaluated NAC protective effects on cognitive impairment and associated
pathological markers in a streptozotocin (STZ)-induced sporadic dementia of AD
type mice model. Animals were divided into six groups: I) Sham, II) NAC, III)
physostigmine (PHY), IV) STZ, V) NAC + STZ and VI) PHY + NAC. NAC (5 mg/kg) and
PHY (0.25 mg/kg) were administrated orally for 30 consecutive days and STZ (2.5
mg/kg) intracerebroventricularly at the first and third days. Novel object
recognition (NOR, days 26-27) and Morris water maze (MWM, days 26-30) tasks were
assessed to evaluate learning and memory. On the thirty-first day animals were
euthanized and brains collected for biochemical analysis. Interestingly, our
results showed that STZ treatment induced cognitive impairment in mice in the NOR
and MWM tasks. Both NAC and PHY treatments prevented from this impairment. The
increase in AChE activity and decrease in pTrkB and MnSOD levels caused by STZ in
the cerebral cortex and hippocampus, were prevented by the NAC and PHY
treatments. The decrease in SYN, MAP2 and GFAP expressions were also prevented by
NAC and PHY treatments. In conclusion, NAC treatment prevented the cognitive
impairment induced by STZ, normalizing the AChE activity and rescuing the
synaptic plasticity loss. Our results suggest that NAC is a promising therapeutic
strategy for the treatment of AD.
PMID- 28499987
TI - Evoked potentials in final epoch of self-initiated hand movement: A study in
patients with depth electrodes.
AB - Comparison between the intended and performed motor action can be expected to
occur in the final epoch of a voluntary movement. In search for
electrophysiological correlates of this mental process the purpose of the current
study was to identify intracerebral sites activated in final epoch of self-paced
voluntary movement. Intracerebral EEG was recorded from 235 brain regions of 42
epileptic patients who performed self-paced voluntary movement task. Evoked
potentials starting at 0 to 243ms after the peak of averaged, rectified
electromyogram were identified in 21 regions of 13 subjects. The mean amplitude
value of these late movement potentials (LMP) was 56.4+/-27.5MUV. LMPs were
observed in remote regions of mesiotemporal structures, cingulate, frontal,
temporal, parietal, and occipital cortices. Closely before the LMP onset, a
significant increase of phase synchronization was observed in all EEG record
pairs in 9 of 10 examined subjects; p<0.001, Mann-Whitney U test. In conclusion,
mesiotemporal structures, cingulate, frontal, temporal, parietal, and occipital
cortices seem to represent integral functionally linked parts of network
activated in final epoch of self-paced voluntary movement. Activation of this
large-scale neuronal network was suggested to reflect a comparison process
between the intended and actually performed motor action. Our results contribute
to better understanding of neural mechanisms underlying goal-directed behavior
crucial for creation of agentive experience.
PMID- 28499989
TI - Melanocortin Receptor Accessory Proteins (MRAPs): Functions in the melanocortin
system and beyond.
AB - G-protein coupled receptors (GPCRs) are regulated by numerous proteins including
kinases, G-proteins, beta-arrestins and accessory proteins. Several families of
GPCR accessory proteins like Receptor Activity Modifying Proteins, Receptor
Transporting Proteins and Melanocortin Receptor Accessory Proteins (MRAPs) have
been identified as regulator of receptor trafficking, signaling and ligand
specificity. The MRAP family contains two members, MRAP1 and MRAP2, responsible
for the formation of a functional ACTH receptor and for the regulation of energy
homeostasis respectively. Like all known GPCR accessory proteins, MRAPs are
single transmembrane proteins, however, they form a unique structure since they
assemble as an anti-parallel homodimer. Moreover, the accepted idea that MRAPs
are specific regulators of melanocortin receptors was recently challenged by the
discovery that MRAP2 inhibits the activity of prokineticin receptors. Recent
studies are starting to explain the role of the unusual structure of MRAPs and to
illustrate the importance of MRAP2 for the maintenance of both energy and glucose
homeostasis. This article is part of a Special Issue entitled: Melanocortin
Receptors - edited by Ya-Xiong Tao.
PMID- 28499991
TI - An Interactive Simulator for Imposing Virtual Musculoskeletal Dynamics.
AB - OBJECTIVE: disease processes are often marked by both neural and muscular changes
that alter movement control and execution, but these adaptations are difficult to
tease apart because they occur simultaneously. This is addressed by swapping an
individual's limb dynamics with a neurally controlled facsimile using an
interactive musculoskeletal simulator (IMS) that allows controlled modifications
of musculoskeletal dynamics. This paper details the design and operation of the
IMS, quantifies and describes human adaptation to the IMS, and determines whether
the IMS allows users to move naturally, a prerequisite for manipulation
experiments. METHODS: healthy volunteers (n = 4) practiced a swift goal-directed
task (back-and-forth elbow flexion/extension) for 90 trials with the IMS off
(normal dynamics) and 240 trials with the IMS on, i.e., the actions of a user's
personalized electromyography-driven musculoskeletal model are robotically
imposed back onto the user. RESULTS: after practicing with the IMS on, subjects
could complete the task with end-point errors of 1.56 degrees , close to the
speed-matched IMS-off error of 0.57 degrees . Muscle activity, joint torque, and
arm kinematics for IMS-on and -off conditions were well matched for three
subjects (root-mean-squared error [RMSE] = 0.16 N.m), but the error was higher
for one subject with a small stature (RMSE = 0.25 N.m). CONCLUSION: a well
matched musculoskeletal model allowed IMS users to perform a goal-directed task
nearly as well as when the IMS was not active. SIGNIFICANCE: this advancement
permits real-time manipulations of musculoskeletal dynamics, which could increase
our understanding of muscular and neural co-adaptations to injury, disease,
disuse, and aging.
PMID- 28499992
TI - Segmentation and Quantification for Angle-Closure Glaucoma Assessment in Anterior
Segment OCT.
AB - Angle-closure glaucoma is a major cause of irreversible visual impairment and can
be identified by measuring the anterior chamber angle (ACA) of the eye. The ACA
can be viewed clearly through anterior segment optical coherence tomography (AS
OCT), but the imaging characteristics and the shapes and locations of major
ocular structures can vary significantly among different AS-OCT modalities, thus
complicating image analysis. To address this problem, we propose a data-driven
approach for automatic AS-OCT structure segmentation, measurement, and screening.
Our technique first estimates initial markers in the eye through label transfer
from a hand-labeled exemplar data set, whose images are collected over different
patients and AS-OCT modalities. These initial markers are then refined by using a
graph-based smoothing method that is guided by AS-OCT structural information.
These markers facilitate segmentation of major clinical structures, which are
used to recover standard clinical parameters. These parameters can be used not
only to support clinicians in making anatomical assessments, but also to serve as
features for detecting anterior angle closure in automatic glaucoma screening
algorithms. Experiments on Visante AS-OCT and Cirrus high-definition-OCT data
sets demonstrate the effectiveness of our approach.
PMID- 28499990
TI - A State Space and Density Estimation Framework for Sleep Staging in Obstructive
Sleep Apnea.
AB - OBJECTIVE: Although the importance of sleep is increasingly recognized, the lack
of robust and efficient algorithms hinders scalable sleep assessment in healthy
persons and those with sleep disorders. Polysomnography (PSG) and visual/manual
scoring remain the gold standard in sleep evaluation, but more
efficient/automated systems are needed. Most previous works have demonstrated
algorithms in high agreement with the gold standard in healthy/normal (HN)
individuals-not those with sleep disorders. METHODS: This paper presents a
statistical framework that automatically estimates whole-night sleep architecture
in patients with obstructive sleep apnea (OSA)-the most common sleep disorder.
Single-channel frontal electroencephalography was extracted from 65 HN/OSA sleep
studies, and decomposed into 11 spectral features in 60 903 30 s sleep epochs.
The algorithm leveraged kernel density estimation to generate stage-specific
likelihoods, and a 5-state hidden Markov model to estimate per-night sleep
architecture. RESULTS: Comparisons to full PSG expert scoring revealed the
algorithm was in fair agreement with the gold standard (median Cohen's kappa =
0.53). Further, analysis revealed modest decreases in median scoring agreement as
OSA severity increased from HN (kappa = 0.63) to severe (kappa = 0.47). A
separate implementation on HN data from the Physionet Sleep-EDF Database resulted
in a median kappa = 0.65, further indicating the algorithm's broad applicability.
CONCLUSION: Results of this work indicate the proposed single-channel framework
can emulate expert-level scoring of sleep architecture in OSA. SIGNIFICANCE:
Algorithms constructed to more accurately model physiological variability during
sleep may help advance automated sleep assessment, for practical and general use
in sleep medicine.
PMID- 28499993
TI - Robust 2-D-3-D Registration Optimization for Motion Compensation During 3-D TRUS
Guided Biopsy Using Learned Prostate Motion Data.
AB - In magnetic resonance (MR)-targeted, 3-D transrectal ultrasound (TRUS)-guided
biopsy, prostate motion during the procedure increases the needle targeting error
and limits the ability to accurately sample MR-suspicious tumor volumes. The
robustness of the 2-D-3-D registration methods for prostate motion compensation
is impacted by local optima in the search space. In this paper, we analyzed the
prostate motion characteristics and investigated methods to incorporate such
knowledge into the registration optimization framework to improve robustness
against local optima. Rigid motion of the prostate was analyzed adopting a
mixture-of-Gaussian (MoG) model using 3-D TRUS images acquired at bilateral
sextant probe positions with a mechanically assisted biopsy system. The learned
motion characteristics were incorporated into Powell's direction set method by
devising multiple initial search positions and initial search directions.
Experiments were performed on data sets acquired during clinical biopsy
procedures, and registration error was evaluated using target registration error
(TRE) and converged image similarity metric values after optimization. After
incorporating the learned initialization positions and directions in Powell's
method, 2-D-3-D registration to compensate for motion during prostate biopsy was
performed with rms +/- std TRE of 2.33 +/- 1.09 mm with ~3 s mean execution time
per registration. This was an improvement over 3.12 +/- 1.70 mm observed in
Powell's standard approach. For the data acquired under clinical protocols, the
converged image similarity metric value improved in >=8% of the registrations
whereas it degraded only <=1% of the registrations. The reported improvements in
optimization indicate useful advancements in robustness to ensure smooth clinical
integration of a registration solution for motion compensation that facilitates
accurate sampling of the smallest clinically significant tumors.
PMID- 28499994
TI - Observation of Nonlinear Harmonic Generation of Bulk Modes in SAW Devices.
AB - Nonlinear generation of harmonics is measured on the wafer level on temperature
compensated surface-acoustic-wave resonators on lithium niobate. The second
harmonic response features strong peaks looking like multiple resonant modes. The
product of the frequency difference between the successive peaks to the substrate
thickness is found to remain almost constant. The results also show that the
level of the harmonic signal strongly depends on the roughness of the back side
of the substrate. Due to these findings, it was assumed that the signal is due to
nonlinear generation of a bulk mode. This assumption is confirmed experimentally
by measuring the second-harmonic wave field on the back side of the substrate
with an interferometer. Possible nonlinear mechanisms explaining these results
are discussed.
PMID- 28499995
TI - Large-Scale Nonlinear Lumped and Integrated Field Simulations of Top-Orthogonal
to-Bottom-Electrode CMUT Architectures.
AB - Capacitive micromachined ultrasonic transducers (CMUTs) promise many advantages
over traditional piezoelectric transducers such as the potential to construct
large, cost-effective 2-D arrays. To avoid wiring congestion issues associated
with fully wired arrays, top-orthogonal-to-bottom electrode (TOBE) CMUT array
architectures have proven to be a more practical alternative, using only 2N wires
for an N *N array. Optimally designing a TOBE CMUT array is a significant
challenge due to the range of parameters from the device level up to the
operating conditions of the entire array. Since testing many design variations
can be prohibitively expensive, a simulation approach accounting for both the
small and large-scale array characteristics of TOBE arrays is essential. In this
paper, we demonstrate large-scale TOBE CMUT array simulations using a nonlinear
CMUT lumped-circuit model. We investigate the performance of the array with
different CMUT design parameters and array operating conditions. These simulated
results are then compared with measurements of TOBE arrays fabricated using a
sacrificial release process.
PMID- 28499996
TI - Modeling and Analysis of Lateral Propagation of Surface Acoustic Waves Including
Coupling Between Different Waves.
AB - This paper discusses lateral propagation of surface acoustic waves (SAWs) in
periodic grating structures when two types of SAWs exist simultaneously and are
coupled. The thin plate model proposed by the authors is extended to include the
coupling between two different SAW modes. First, lateral SAW propagation in an
infinitely long periodic grating is modeled and discussed. Then, the model is
applied to the Al-grating/42 degrees YX-LiTaO3 (42-LT) substrate structure, and
it is shown that the slowness curve shape changes from concave to convex with the
Al grating thickness. The transverse responses are also analyzed on an infinitely
long interdigital transducer on the structure, and good agreement is achieved
between the present and the finite-element method analyses. Finally, SAW
resonators are fabricated on the Cu grating/42-LT substrate structure, and it is
experimentally verified that the slowness curve shape of the shear horizontal SAW
changes with the Cu thickness.
PMID- 28499988
TI - Melanocortin neurons: Multiple routes to regulation of metabolism.
AB - The burden of disability, premature death, escalating health care costs and lost
economic productivity due to obesity and its associated complications including
hypertension, stroke, cardiovascular disease and type 2 diabetes is staggering
[1,2]. A better understanding of metabolic homeostatic pathways will provide us
with insights into the biological mechanisms of obesity and how to fundamentally
address this epidemic [3-6]. In mammals, energy balance is maintained via a
homeostatic system involving both peripheral and central melanocortin systems;
changes in body weight reflect an unbalance of the energetic state [7-9].
Although the primary cause of obesity is unknown, there is significant effort to
understand the role of the central melanocortin pathway in the brain as it has
been shown that deficiency of proopiomelanocortin (POMC) [10,11] and melanocortin
4 receptors (MC4R) [12-15] in both rodents and humans results in severe
hyperphagia and obesity [16-23]. In this review, we will summarize how the
central melanocortin pathway helps regulate body mass and adiposity within a
'healthy' range through the 'nutrient sensing' network [24-28]. This article is
part of a Special Issue entitled: Melanocortin Receptors - edited by Ya-Xiong
Tao.
PMID- 28499997
TI - Enhancement of Visual Comfort and Sense of Presence on Stereoscopic 3D Images.
AB - Conventional stereoscopic 3D (S3D) displays do not provide accommodation depth
cues of the 3D image or video contents being viewed. The sense of content depths
is thus limited to cues supplied by motion parallax (for 3D video), stereoscopic
vergence cues created by presenting left and right views to the respective eyes,
and other contextual and perspective depth cues. The absence of accommodation
cues can induce two kinds of accommodation vergence mismatches (AVM) at the
fixation and peripheral points, which can result in severe visual discomfort.
With the aim of alleviating discomfort arising from AVM, we propose a new visual
comfort enhancement approach for processing S3D visual signals to deliver a more
comfortable 3D viewing experience at the display. This is accomplished via an
optimization process whereby a predictive indicator of visual discomfort is
minimized, while still aiming to maintain the viewer's sense of 3D presence by
performing a suitable parallax shift, and by directed blurring of the signal. Our
processing framework is defined on 3D visual coordinates that reflect the
nonuniform resolution of retinal sensors and that uses a measure of 3D saliency
strength. An appropriate level of blur that corresponds to the degree of parallax
shift is found, making it possible to produce synthetic accommodation cues
implemented using a perceptively relevant filter. By this method, AVM, the
primary contributor to the discomfort felt when viewing S3D images, is reduced.
We show via a series of subjective experiments that the proposed approach
improves visual comfort while preserving the sense of 3D presence.
PMID- 28499998
TI - Scalable Image Coding Based on Epitomes.
AB - In this paper, we propose a novel scheme for scalable image coding based on the
concept of epitome. An epitome can be seen as a factorized representation of an
image. Focusing on spatial scalability, the enhancement layer of the proposed
scheme contains only the epitome of the input image. The pixels of the
enhancement layer not contained in the epitome are then restored using two
approaches inspired from local learning-based super-resolution methods. In the
first method, a locally linear embedding model is learned on base layer patches
and then applied to the corresponding epitome patches to reconstruct the
enhancement layer. The second approach learns linear mappings between pairs of co
located base layer and epitome patches. Experiments have shown that the
significant improvement of the rate-distortion performances can be achieved
compared with the Scalable extension of HEVC (SHVC).
PMID- 28499999
TI - Contrast Enhancement Based on Intrinsic Image Decomposition.
AB - In this paper, we propose to introduce intrinsic image decomposition priors into
decomposition models for contrast enhancement. Since image decomposition is a
highly illposed problem, we introduce constraints on both reflectance and
illumination layers to yield a highly reliable solution. We regularize the
reflectance layer to be piecewise constant by introducing a weighted l1 norm
constraint on neighboring pixels according to the color similarity, so that the
decomposed reflectance would not be affected much by the illumination
information. The illumination layer is regularized by a piecewise smoothness
constraint. The proposed model is effectively solved by the Split Bregman
algorithm. Then, by adjusting the illumination layer, we obtain the enhancement
result. To avoid potential color artifacts introduced by illumination adjusting
and reduce computing complexity, the proposed decomposition model is performed on
the value channel in HSV space. Experiment results demonstrate that the proposed
method performs well for a wide variety of images, and achieves better or
comparable subjective and objective quality compared with the state-of-the-art
methods.
PMID- 28500000
TI - Hierarchical Contour Closure-Based Holistic Salient Object Detection.
AB - Most existing salient object detection methods compute the saliency for pixels,
patches, or superpixels by contrast. Such fine-grained contrast-based salient
object detection methods are stuck with saliency attenuation of the salient
object and saliency overestimation of the background when the image is
complicated. To better compute the saliency for complicated images, we propose a
hierarchical contour closure-based holistic salient object detection method, in
which two saliency cues, i.e., closure completeness and closure reliability, are
thoroughly exploited. The former pops out the holistic homogeneous regions
bounded by completely closed outer contours, and the latter highlights the
holistic homogeneous regions bounded by averagely highly reliable outer contours.
Accordingly, we propose two computational schemes to compute the corresponding
saliency maps in a hierarchical segmentation space. Finally, we propose a
framework to combine the two saliency maps, obtaining the final saliency map.
Experimental results on three publicly available datasets show that even each
single saliency map is able to reach the state-of-the-art performance.
Furthermore, our framework, which combines two saliency maps, outperforms the
state of the arts. Additionally, we show that the proposed framework can be
easily used to extend existing methods and further improve their performances
substantially.
PMID- 28500001
TI - Exemplar-Based Image and Video Stylization Using Fully Convolutional Semantic
Features.
AB - Color and tone stylization in images and videos strives to enhance unique themes
with artistic color and tone adjustments. It has a broad range of applications
from professional image postprocessing to photo sharing over social networks.
Mainstream photo enhancement softwares, such as Adobe Lightroom and Instagram,
provide users with predefined styles, which are often hand-crafted through a
trial-and-error process. Such photo adjustment tools lack a semantic
understanding of image contents and the resulting global color transform limits
the range of artistic styles it can represent. On the other hand, stylistic
enhancement needs to apply distinct adjustments to various semantic regions. Such
an ability enables a broader range of visual styles. In this paper, we first
propose a novel deep learning architecture for exemplar-based image stylization,
which learns local enhancement styles from image pairs. Our deep learning
architecture consists of fully convolutional networks for automatic semantics
aware feature extraction and fully connected neural layers for adjustment
prediction. Image stylization can be efficiently accomplished with a single
forward pass through our deep network. To extend our deep network from image
stylization to video stylization, we exploit temporal superpixels to facilitate
the transfer of artistic styles from image exemplars to videos. Experiments on a
number of data sets for image stylization as well as a diverse set of video clips
demonstrate the effectiveness of our deep learning architecture.
PMID- 28500002
TI - Cross-Label Suppression: A Discriminative and Fast Dictionary Learning With Group
Regularization.
AB - This paper addresses image classification through learning a compact and
discriminative dictionary efficiently. Given a structured dictionary with each
atom (columns in the dictionary matrix) related to some label, we propose
crosslabel suppression constraint to enlarge the difference among representations
for different classes. Meanwhile, we introduce group regularization to enforce
representations to preserve label properties of original samples, meaning the
representations for the same class are encouraged to be similar. Upon the
crosslabel suppression, we donot resort to frequently-used l0-norm or l1-norm for
coding, and obtain computational efficiency without losing the discriminative
power for categorization. Moreover, two simple classification schemes are also
developed to take full advantage of the learnt dictionary. Extensive experiments
on six data sets, including face recognition, object categorization, scene
classification, texture recognition, and sport action categorization are
conducted, and the results show that the proposed approach can outperform lots of
recently presented dictionary algorithms on both recognition accuracy and
computational efficiency.
PMID- 28500003
TI - Hybrid Laplace Distribution-Based Low Complexity Rate-Distortion Optimized
Quantization.
AB - Rate distortion optimized quantization (RDOQ) is an efficient encoder
optimization method that plays an important role in improving the rate-distortion
(RD) performance of the high-efficiency video coding (HEVC) codecs. However, the
superior performance of RDOQ is achieved at the expense of high computational
complexity cost in two stages RD minimization, including the determination of
optimal quantized level among available candidates for each transformed
coefficient and the determination of best quantized coefficients for transform
units with the minimum total cost, to softly optimize the quantized coefficients.
To reduce the computational cost of the RDOQ algorithm in HEVC, we propose a low
complexity RDOQ scheme by modeling the statistics of the transform coefficients
with hybrid Laplace distribution. In this manner, specifically designed block
level rate and distortion models are established based on the coefficient
distribution. Therefore, the optimal quantization levels can be directly
determined by optimizing the RD performance of the whole block, while the
complicated RD cost calculations can be eventually avoided. Extensive
experimental results show that with about 0.3%-0.4% RD performance degradation,
the proposed low-complexity RDOQ algorithm is able to reduce around 70%
quantization time with up to 17% total encoding time reduction compared with the
original RDOQ implementation in HEVC on average.
PMID- 28500004
TI - Generic Content-Based Retrieval of Marker-Based Motion Capture Data.
AB - In this work, we propose an original scheme for generic content-based retrieval
of marker-based motion capture data. It works on motion capture data of arbitrary
subject types and arbitrary marker attachment and labelling conventions.
Specifically, we propose a novel motion signature to statistically describe both
the high-level and the low-level morphological and kinematic characteristics of a
motion capture sequence, and conduct the content-based retrieval by computing and
ordering the motion signature distance between the query and every item in the
database. The distance between two motion signatures is computed by a weighted
sum of differences in separate features contained in them. For maximum retrieval
performance, we propose a method to pre-learn an optimal set of weights for each
type of motion in the database through biased discriminant analysis, and
adaptively choose a good set of weights for any given query at the run time.
Excellence of the proposed scheme is experimentally demonstrated on various data
sets and performance metrics.
PMID- 28500005
TI - Patch-Based Image Inpainting via Two-Stage Low Rank Approximation.
AB - To recover the corrupted pixels, traditional inpainting methods based on low-rank
priors generally need to solve a convex optimization problem by an iterative
singular value shrinkage algorithm. In this paper, we propose a simple method for
image inpainting using low rank approximation, which avoids the time-consuming
iterative shrinkage. Specifically, if similar patches of a corrupted image are
identified and reshaped as vectors, then a patch matrix can be constructed by
collecting these similar patch-vectors. Due to its columns being highly linearly
correlated, this patch matrix is low-rank. Instead of using an iterative singular
value shrinkage scheme, the proposed method utilizes low rank approximation with
truncated singular values to derive a closed-form estimate for each patch matrix.
Depending upon an observation that there exists a distinct gap in the singular
spectrum of patch matrix, the rank of each patch matrix is empirically determined
by a heuristic procedure. Inspired by the inpainting algorithms with component
decomposition, a two-stage low rank approximation (TSLRA) scheme is designed to
recover image structures and refine texture details of corrupted images.
Experimental results on various inpainting tasks demonstrate that the proposed
method is comparable and even superior to some state-of-the-art inpainting
algorithms.
PMID- 28500006
TI - Skill Learning and Skill Transfer Mediated by Cooperative Haptic Interaction.
AB - It is known that physical coupling between two subjects may be advantageous in
joint tasks. However, little is known about how two people mutually exchange
information to exploit the coupling. Therefore, we adopted a reversed, novel
perspective to the standard one that focuses on the ability of physically coupled
subjects to adapt to cooperative contexts that require negotiating a common plan:
we investigated how training in pairs on a novel task affects the development of
motor skills of each of the interacting partners. The task involved reaching
movements in an unstable dynamic environment using a bilateral non-linear elastic
tool that could be used bimanually or dyadically. The main result is that
training with an expert leads to the greatest performance in the joint task.
However, the performance in the individual test is strongly affected by the
initial skill level of the partner. Moreover, practicing with a peer rather than
an expert appears to be more advantageous for a naive; and motor skills can be
transferred to a bimanual context, after training with an expert, only if the non
expert subject had prior experience of the dynamics of the novel task.
PMID- 28500007
TI - A Wearable Multi-Site System for NMES-Based Hand Function Restoration.
AB - Reaching and grasping impairments significantly affect the quality of life for
people who have experienced a stroke or spinal cord injury. The long-term well
being of patients varies greatly according to the restorable residual
capabilities. Electrical stimulation could be a promising solution to restore
motor functions in these conditions, but its use is not clinically widespread.
Here, we introduce the HandNMES, an electrode array (EA) for neuromuscular
electrical stimulation (NMES) aimed at grasp training and assistance. The device
was designed to deliver electrical stimulation to extrinsic and intrinsic hand
muscles. Six independent EAs, positioned on the user forearm and hand, deliver
NMES pulses originating from an external stimulator equipped with demultiplexers
for interfacing with a large number of electrodes. The garment was designed to be
adaptable to user needs and anthropometric characteristics; size, shape, and
contact materials can be customized, and stimulation characteristics such as
intensity of stimulation and virtual electrode location, and size can be
adjusted. We performed extensive tests with nine healthy subjects showing the
efficacy of the HandNMES in terms of stimulation performance and personalization.
Because encouraging results were achieved, in the coming months, the HandNMES
device will be tested in pilot clinical trials.
PMID- 28500008
TI - Wearable Haptic Systems for the Fingertip and the Hand: Taxonomy, Review, and
Perspectives.
AB - In the last decade, we have witnessed a drastic change in the form factor of
audio and vision technologies, from heavy and grounded machines to lightweight
devices that naturally fit our bodies. However, only recently, haptic systems
have started to be designed with wearability in mind. The wearability of haptic
systems enables novel forms of communication, cooperation, and integration
between humans and machines. Wearable haptic interfaces are capable of
communicating with the human wearers during their interaction with the
environment they share, in a natural and yet private way. This paper presents a
taxonomy and review of wearable haptic systems for the fingertip and the hand,
focusing on those systems directly addressing wearability challenges. The paper
also discusses the main technological and design challenges for the development
of wearable haptic interfaces, and it reports on the future perspectives of the
field. Finally, the paper includes two tables summarizing the characteristics and
features of the most representative wearable haptic systems for the fingertip and
the hand.
PMID- 28500009
TI - End-to-End Feature-Aware Label Space Encoding for Multilabel Classification With
Many Classes.
AB - To make the problem of multilabel classification with many classes more
tractable, in recent years, academia has seen efforts devoted to performing label
space dimension reduction (LSDR). Specifically, LSDR encodes high-dimensional
label vectors into low-dimensional code vectors lying in a latent space, so as to
train predictive models at much lower costs. With respect to the prediction, it
performs classification for any unseen instance by recovering a label vector from
its predicted code vector via a decoding process. In this paper, we propose a
novel method, namely End-to-End Feature-aware label space Encoding (E2FE), to
perform LSDR. Instead of requiring an encoding function like most previous works,
E2FE directly learns a code matrix formed by code vectors of the training
instances in an end-to-end manner. Another distinct property of E2FE is its
feature awareness attributable to the fact that the code matrix is learned by
jointly maximizing the recoverability of the label space and the predictability
of the latent space. Based on the learned code matrix, E2FE further trains
predictive models to map instance features into code vectors, and also learns a
linear decoding matrix for efficiently recovering the label vector of any unseen
instance from its predicted code vector. Theoretical analyses show that both the
code matrix and the linear decoding matrix in E2FE can be efficiently learned.
Moreover, similar to previous works, E2FE can be specified to learn an encoding
function. And it can also be extended with kernel tricks to handle nonlinear
correlations between the feature space and the latent space. Comprehensive
experiments conducted on diverse benchmark data sets with many classes show
consistent performance gains of E2FE over the state-of-the-art methods.
PMID- 28500010
TI - Robust Latent Subspace Learning for Image Classification.
AB - This paper proposes a novel method, called robust latent subspace learning
(RLSL), for image classification. We formulate an RLSL problem as a joint
optimization problem over both the latent SL and classification model parameter
predication, which simultaneously minimizes: 1) the regression loss between the
learned data representation and objective outputs and 2) the reconstruction error
between the learned data representation and original inputs. The latent subspace
can be used as a bridge that is expected to seamlessly connect the origin visual
features and their class labels and hence improve the overall prediction
performance. RLSL combines feature learning with classification so that the
learned data representation in the latent subspace is more discriminative for
classification. To learn a robust latent subspace, we use a sparse item to
compensate error, which helps suppress the interference of noise via weakening
its response during regression. An efficient optimization algorithm is designed
to solve the proposed optimization problem. To validate the effectiveness of the
proposed RLSL method, we conduct experiments on diverse databases and encouraging
recognition results are achieved compared with many state-of-the-arts methods.
PMID- 28500011
TI - Improved Stability and Stabilization Results for Stochastic Synchronization of
Continuous-Time Semi-Markovian Jump Neural Networks With Time-Varying Delay.
AB - Continuous-time semi-Markovian jump neural networks (semi-MJNNs) are those MJNNs
whose transition rates are not constant but depend on the random sojourn time.
Addressing stochastic synchronization of semi-MJNNs with time-varying delay, an
improved stochastic stability criterion is derived in this paper to guarantee
stochastic synchronization of the response systems with the drive systems. This
is achieved through constructing a semi-Markovian Lyapunov-Krasovskii functional
together as well as making use of a novel integral inequality and the
characteristics of cumulative distribution functions. Then, with a linearization
procedure, controller synthesis is carried out for stochastic synchronization of
the drive-response systems. The desired state-feedback controller gains can be
determined by solving a linear matrix inequality-based optimization problem.
Simulation studies are carried out to demonstrate the effectiveness and less
conservatism of the presented approach.
PMID- 28500012
TI - Memcomputing Numerical Inversion With Self-Organizing Logic Gates.
AB - We propose to use digital memcomputing machines (DMMs), implemented with self
organizing logic gates (SOLGs), to solve the problem of numerical inversion.
Starting from fixed-point scalar inversion, we describe the generalization to
solving linear systems and matrix inversion. This method, when realized in
hardware, will output the result in only one computational step. As an example,
we perform simulations of the scalar case using a 5-bit logic circuit made of
SOLGs, and show that the circuit successfully performs the inversion. Our method
can be extended efficiently to any level of precision, since we prove that
producing -bit precision in the output requires extending the circuit by at most
bits. This type of numerical inversion can be implemented by DMM units in
hardware; it is scalable, and thus of great benefit to any real-time computing
application.
PMID- 28500013
TI - New Splitting Criteria for Decision Trees in Stationary Data Streams.
AB - The most popular tools for stream data mining are based on decision trees. In
previous 15 years, all designed methods, headed by the very fast decision tree
algorithm, relayed on Hoeffding's inequality and hundreds of researchers followed
this scheme. Recently, we have demonstrated that although the Hoeffding decision
trees are an effective tool for dealing with stream data, they are a purely
heuristic procedure; for example, classical decision trees such as ID3 or CART
cannot be adopted to data stream mining using Hoeffding's inequality. Therefore,
there is an urgent need to develop new algorithms, which are both mathematically
justified and characterized by good performance. In this paper, we address this
problem by developing a family of new splitting criteria for classification in
stationary data streams and investigating their probabilistic properties. The new
criteria, derived using appropriate statistical tools, are based on the
misclassification error and the Gini index impurity measures. The general
division of splitting criteria into two types is proposed. Attributes chosen
based on type- splitting criteria guarantee, with high probability, the highest
expected value of split measure. Type- criteria ensure that the chosen attribute
is the same, with high probability, as it would be chosen based on the whole
infinite data stream. Moreover, in this paper, two hybrid splitting criteria are
proposed, which are the combinations of single criteria based on the
misclassification error and Gini index.
PMID- 28500014
TI - Three-Dimensional Visual Patient Based on Electronic Medical Diagnostic Records.
AB - OBJECTIVE: an innovative concept and method is introduced to use a 3-D anatomical
graphic pattern called visual patient (VP) visually to index, represent, and
render the medical diagnostic records (MDRs) of a patient, so that a doctor can
quickly learn the current and historical medical status of the patient by
manipulating VP. The MDRs can be imaging diagnostic reports and DICOM images,
laboratory reports and clinical summaries which can have clinical information
relating to medical status of human organs or body parts. METHODS: the concept
and method included three steps. First, a VP data model called visual index
object (VIO) and a VP graphic model called visual anatomic object (VAO) were
introduced. Second, a series of processing methods of parsing and extracting key
information from MDRs were used to fill the attributes of the VIO model of a
patient. Third, a VP system (VPS) was designed to map VIO to VAO, to create a VP
instance for each patient. RESULTS: a prototype VPS has been implemented in a
simulated hospital PACS/RIS integrated environment. Two evaluation results showed
that more than 70% participating radiologists would like to use the VPS in their
radiological imaging tasks, and the efficiency of using VPS to review the tested
patients' MDRs was 2.24 times higher than that of using PACS/RIS, while the
average accuracy by using PACS/RIS was better than that by using VPS;
however, this difference was only about 4%. CONCLUSION: the developed VPS can
show the medical status of patient organs/sub-organs with 3-D anatomical graphic
pattern and will be welcomed by radiologists with better efficiency in reviewing
the patients' MDRs and with acceptable accuracy. SIGNIFICANCE: the VP introduces
a new way for medical professionals to access and interact with a huge amount of
patient records with better efficiency in the big data era.
PMID- 28500015
TI - Social Synchrony on Complex Networks.
AB - Social synchrony (SS) is an emergent phenomenon in human society. People often
mimic others which, over time, can result in large groups behaving similarly.
Drawing from prior empirical studies of SS in online communities, here we propose
a discrete network model of SS based on four attributes: 1) depth of action; 2)
breadth of impact, i.e., a large number of actions are performed with a large
group of people involved; 3) heterogeneity of role, i.e., people of higher degree
play more important roles; and 4) lastly, emergence of phenomenon, i.e., it is
far from random. We analyze our model both analytically and with simulations, and
find good agreement between the two. We find this model can well explain the four
characters of SS, and thus hope it can help researchers better understand human
collective behavior.
PMID- 28500016
TI - Adaptive Graph Matching.
AB - Establishing correspondence between point sets lays the foundation for many
computer vision and pattern recognition tasks. It can be well defined and solved
by graph matching. However, outliers may significantly deteriorate its
performance, especially when outliers exist in both point sets and meanwhile the
inlier number is unknown. In this paper, we propose an adaptive graph matching
algorithm to tackle this problem. Specifically, a novel formulation is proposed
to make the graph matching model adaptively determine the number of inliers and
match them, then by relaxing the discrete domain to its convex hull the discrete
optimization problem is relaxed to be a continuous one, and finally a graduated
projection scheme is used to get a discrete matching solution. Consequently, the
proposed algorithm could realize inlier number estimation, inlier selection, and
inlier matching in one optimization framework. Experiments on both synthetic data
and real world images witness the effectiveness of the proposed algorithm.
PMID- 28500017
TI - Tablet-Based Well-Being Check for the Elderly: Development and Evaluation of
Usability and Acceptability.
AB - BACKGROUND: Many elderly people prefer to live at home independently. One of the
major concerns raised by the family members is the safety and well-being of their
elderly family members when living independently in a home environment. To
address this issue, assistive technology solutions have been available in the
market. Despite their availability and proliferation, these types of solutions
are not popular with the elderly due to their intrusive nature, privacy-related
issues, social stigma, and fear of losing human interaction. This study shares
the experience in the development of a digital photo frame system that helps
family members to check the well-being of the elderly, exploiting their desire to
remain socially connected. OBJECTIVES: The aim of this study was to iteratively
design, implement, and assess the usability, user friendliness, and acceptability
of a tablet-based system to check the well-being of the elderly. METHODS: Our
study methodology comprises three separate stages: initial system development,
contextual assessment, and comparative case study evaluation. RESULTS: In the
first stage, requirements were elicited from the elderly to design a well-being
check prototype. In the second stage, areas for improvements (eg, privacy
features) were identified. Also, additional features (such as medication prompts
or food reminders) were suggested to help aged and health care service providers
with effective but subtle monitoring of the elderly. These would lower their
operating cost by reducing visits by care providers to the homes of the elderly.
In the third stage, the results highlighted the difference (between users in
India and Australia) in the levels of familiarity of the elderly with this
technology. Some elderly participants at the Kalyani Institute for Study,
Planning and Action for Rural Change, India latched onto this technology quickly
while a few refused to use the system. However, in all cases, the support of
family members was crucial for their willingness to use the technology.
CONCLUSIONS: This project has three major outcomes. First, a picture frame
prototype was tested with the elderly to leverage the benefits of social
communication. Second, the project helped us test and implement the "Silvercare"
model for supporting the elderly through young retired people residing in the
area. Finally, the project helped formalize the agile three-stage design
methodology to develop information technology solutions for the elderly. Also,
the project contributed to an ongoing European Union Project called Victoryahome,
which involves more than 50 sites across 5 countries (Norway, Sweden,
Netherlands, Portugal, and Australia) to assess the use of telepresence robots,
wearable fall detectors, and medication dispensers for the elderly living
independently.
PMID- 28500018
TI - Guidelines for the Gamification of Self-Management of Chronic Illnesses:
Multimethod Study.
AB - BACKGROUND: Gamification is the use of game elements and techniques in nongaming
contexts. The use of gamification in health care is receiving a great deal of
attention in both academic research and the industry. However, it can be noticed
that many gamification apps in health care do not follow any standardized
guidelines. OBJECTIVE: This research aims to (1) present a set of guidelines
based on the validated framework the Wheel of Sukr and (2) assess the guidelines
through expert interviews and focus group sessions with developers. METHODS:
Expert interviews (N=6) were conducted to assess the content of the guidelines
and that they reflect the Wheel of Sukr. In addition, the guidelines were
assessed by developers (N=15) in 5 focus group sessions, where each group had an
average of 3 developers. RESULTS: The guidelines received support from the
experts. By the end of the sixth interview, it was determined that a saturation
point was reached. Experts agreed that the guidelines accurately reflect the
framework the Wheel of Sukr and that developers can potentially use them to
create gamified self-management apps for chronic illnesses. Moreover, the
guidelines were welcomed by developers who participated in the focus group
sessions. They found the guidelines to be clear, useful, and implementable. Also,
they were able to suggest many ways of gamifying a nongamified self-management
app when they were presented with one. CONCLUSIONS: The findings suggest that the
guidelines introduced in this research are clear, useful, and ready to be
implemented for the creation of self-management apps that use the notion of
gamification as described in the Wheel of Sukr framework. The guidelines are now
ready to be practically tested. Further practical studies of the effectiveness of
each element in the guidelines are to be carried out.
PMID- 28500019
TI - Assessing the Comparability of Paper and Electronic Versions of the EORTC QOL
Module for Head and Neck Cancer: A Qualitative Study.
AB - BACKGROUND: Patient-reported outcome (PRO) instruments are important tools for
monitoring disease activity and response to treatment in clinical trials and
clinical practice. In recent years, there have been movements away from
traditional pen-and-paper PROs towards electronic administration. When using
electronic PROs (ePROs), evidence that respondents complete ePROs in a similar
way to their paper counterparts provides assurance that the two modes of
administration are comparable or equivalent. The European Organisation for
Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30
item (EORTC QLQ-C30) and associated disease-specific modules are among the most
widely used PROs in oncology. Although studies have evaluated the comparability
and equivalence of electronic and original paper versions of the EORTC QLQ-C30,
no such studies have been conducted to date for the head and neck cancer specific
module (EORTC QLQ-H&N35). OBJECTIVE: This study aimed to qualitatively assess the
comparability of paper and electronic versions of the EORTC QLQ-H&N35. METHODS:
Ten head and neck cancer patients in the United States underwent structured
cognitive debriefing and usability interviews. An open randomized crossover
design was used in which participants completed the two modes of administration
allocated in a randomized order. Using a "think-aloud" process, participants were
asked to speak their thoughts aloud while completing the EORTC QLQ-H&N35. They
were thoroughly debriefed on their responses to determine consistency in
interpretation and cognitive process when completing the instrument in both paper
and electronic format. RESULTS: Participants reported that the EORTC QLQ-H&N35
demonstrated excellent qualitative comparability between modes of administration.
The proportion of noncomparable responses (ie, where the thought process used by
participants for selecting responses appeared to be different) observed in the
study was low (11/350 response pairs [35 items x 10 participants]; 3.1%).
Evidence of noncomparability was observed for 9 of the 35 items of the EORTC QLQ
H&N35 and in no more than 2 participants per item. In addition, there were no
apparent differences in level of comparability between individual participants or
between modes of administration. CONCLUSIONS: Mode of administration does not
affect participants' response to, or interpretation of, items in the EORTC QLQ
H&N35. The findings from this study add to the existing evidence supporting the
use of electronic versions of the EORTC instruments when migrated to electronic
platforms according to best practice guidelines.
PMID- 28500021
TI - Thoracic Surgery Information on the Internet: A Multilingual Quality Assessment.
AB - BACKGROUND: Previous data suggest that quality of Internet information regarding
surgical conditions and their treatments is variable. However, no comprehensive
analysis of website quality exists for thoracic surgery. OBJECTIVE: The aim of
this study was to quantify website quality in a multilingual setting using an
international standard for assessment. METHODS: Health On the Net (HON)
principles may be applied to websites using an automated toolbar function. We
used the English, French, Spanish, and German Google search engines to identify
12,000 websites using keywords related to thoracic conditions and procedures. The
first 150 websites returned by each keyword in each language were examined. We
compared website quality to assess for tertile (is the quality better in first,
second, or third 50 websites returned) and language differences. A further
analysis of the English site types was undertaken performing a comparative
analysis of website provider types. RESULTS: Overall, there are a considerable
number of websites devoted to thoracic surgery: "lung cancer" returned over 150
million websites. About 7.85% (940/11,967) of websites are HON-accredited with
differences by search term (P<.001) and tertiles (P<.001) of the first 150
websites, but not between languages. Oncological keywords regarding conditions
and procedures were found to return a higher percentage of HON-accreditation. The
percentage of HON-accredited sites was similar across all four languages (P=.77).
In general, the first tertile contained a higher percentage of HON-accredited
sites for every keyword. CONCLUSIONS: Clinicians should appreciate the lack of
validation of the majority of thoracic websites, with discrepancies in quality
and number of websites across conditions and procedures. These differences appear
similar regardless of language. An opportunity exists for clinicians to
participate in the development of informative, ethical, and reliable health
websites on the Internet and direct patients to them.
PMID- 28500023
TI - An apparently simple case of fever and sore throat.
PMID- 28500024
TI - Anticancer Sulfonamides Induce Splicing Factor RBM39 Degradation.
AB - Anticancer sulfonamides produce aberrant splicing by inducing degradation of the
splicing factor RBM39.
PMID- 28500020
TI - Efficacy of a Web-Based Guided Recommendation Service for a Curated List of
Readily Available Mental Health and Well-Being Mobile Apps for Young People:
Randomized Controlled Trial.
AB - BACKGROUND: Mental disorders are highly prevalent for the people who are aged
between 16 and 25 years and can permanently disrupt the development of these
individuals. Easily available mobile health (mHealth) apps for mobile phones have
great potential for the prevention and early intervention of mental disorders in
young adults, but interventions are required that can help individuals to both
identify high-quality mobile apps and use them to change health and lifestyle
behavior. OBJECTIVES: The study aimed to assess the efficacy of a Web-based self
guided app recommendation service ("The Toolbox") in improving the well-being of
young Australians aged between 16 and 25 years. The intervention was developed in
collaboration with young adults and consists of a curated list of 46 readily
available health and well-being apps, assessed and rated by professionals and
young people. Participants are guided by an interactive quiz and subsequently
receive recommendations for particular apps to download and use based on their
personal goals. METHODS: The study was a waitlist, parallel-arm, randomized
controlled trial. Our primary outcome measure was change in well-being as
measured by the Mental Health Continuum-Short Form (MHC-SF). We also employed
ecological momentary assessments (EMAs) to track mood, energy, rest, and sleep.
Participants were recruited from the general Australian population, via several
Web-based and community strategies. The study was conducted through a Web-based
platform consisting of a landing Web page and capabilities to administer study
measures at different time points. Web-based measurements were self-assessed at
baseline and 4 weeks, and EMAs were collected repeatedly at regular weekly
intervals or ad hoc when participants interacted with the study platform. Primary
outcomes were analyzed using linear mixed-models and intention-to-treat (ITT)
analysis. RESULTS: A total of 387 participants completed baseline scores and were
randomized into the trial. Results demonstrated no significant effect of "The
Toolbox" intervention on participant well-being at 4 weeks compared with the
control group (P=.66). There were also no significant differences between the
intervention and control groups at 4 weeks on any of the subscales of the MHC-SF
(psychological: P=.95, social: P=.42, emotional: P=.95). Repeat engagement with
the study platform resulted in a significant difference in mood, energy, rest,
and sleep trajectories between intervention and control groups as measured by
EMAs (P<.01). CONCLUSIONS: This was the first study to assess the effectiveness
of a Web-based well-being intervention in a sample of young adults. The design of
the intervention utilized expert rating of existing apps and end-user codesign
approaches resulting in an app recommendation service. Our finding suggests that
recommended readily available mental health and well-being apps may not lead to
improvements in the well-being of a nonclinical sample of young people, but might
halt a decline in mood, energy, rest, and sleep. TRIAL REGISTRATION: Australian
New Zealand Clinical Trials Registry (ANZCTR): ACTRN12614000710628;
https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366145 (Archived
by WebCite at http://www.webcitation.org/ 6pWDsnKme).
PMID- 28500022
TI - What Matters in Weight Loss? An In-Depth Analysis of Self-Monitoring.
AB - BACKGROUND: Using technology to self-monitor body weight, dietary intake, and
physical activity is a common practice used by consumers and health companies to
increase awareness of current and desired behaviors in weight loss. Understanding
how to best use the information gathered by these relatively new methods needs to
be further explored. OBJECTIVE: The purpose of this study was to analyze the
contribution of self-monitoring to weight loss in participants in a 6-month
commercial weight-loss intervention administered by Retrofit and to specifically
identify the significant contributors to weight loss that are associated with
behavior and outcomes. METHODS: A retrospective analysis was performed using 2113
participants enrolled from 2011 to 2015 in a Retrofit weight-loss program.
Participants were males and females aged 18 years or older with a starting body
mass index of >=25 kg/m2, who also provided a weight measurement at the sixth
month of the program. Multiple regression analysis was performed using all
measures of self-monitoring behaviors involving weight measurements, dietary
intake, and physical activity to predict weight loss at 6 months. Each
significant predictor was analyzed in depth to reveal the impact on outcome.
RESULTS: Participants in the Retrofit Program lost a mean -5.58% (SE 0.12) of
their baseline weight with 51.87% (1096/2113) of participants losing at least 5%
of their baseline weight. Multiple regression model (R2=.197, P<0.001) identified
the following measures as significant predictors of weight loss at 6 months:
number of weigh-ins per week (P<.001), number of steps per day (P=.02), highly
active minutes per week (P<.001), number of food log days per week (P<.001), and
the percentage of weeks with five or more food logs (P<.001). Weighing in at
least three times per week, having a minimum of 60 highly active minutes per
week, food logging at least three days per week, and having 64% (16.6/26) or more
weeks with at least five food logs were associated with clinically significant
weight loss for both male and female participants. CONCLUSIONS: The self
monitoring behaviors of self-weigh-in, daily steps, high-intensity activity, and
persistent food logging were significant predictors of weight loss during a 6
month intervention.
PMID- 28500027
TI - Engineering CAR T Cells with Biomaterials.
AB - Incorporating biomaterials into the design of CAR T cells may yield new, improved
versions of this immunotherapy. Two preclinical studies indicate the potential of
using biodegradable nanoparticles to program circulating T cells into CAR T cells
in situ, and delivering these therapeutic cells directly to solid tumors via
small dissolvable sponges.
PMID- 28500030
TI - Translating Divergent Environmental Stresses into a Common Proteome Response
through Hik33 in a Model Cyanobacterium.
AB - The histidine kinase Hik33 plays important roles in mediating cyanobacterial
response to divergent types of abiotic stresses including cold, salt, high light
(HL), and osmotic stresses. However, how these functions are regulated by Hik33
remains to be addressed. Using a hik33-deficient strain (Deltahik33) of
Synechocystis sp. PCC 6803 (Synechocystis) and quantitative proteomics, we found
that Hik33 depletion induces differential protein expression highly similar to
that induced by divergent types of stresses. This typically includes
downregulation of proteins in photosynthesis and carbon assimilation that are
necessary for cell propagation, and upregulation of heat shock proteins,
chaperons, and proteases that are important for cell survival. This observation
indicates that depletion of Hik33 alone mimics divergent types of abiotic
stresses, and that Hik33 could be important for preventing abnormal stress
response in the normal condition. Moreover, we found the majority of proteins of
plasmid origin were significantly upregulated in Deltahik33, though their
biological significance remains to be addressed. Together, the systematically
characterized Hik33-regulated cyanobacterial proteome, which is largely involved
in stress responses, builds the molecular basis for Hik33 as a general regulator
of stress responses.
PMID- 28500031
TI - Labeling glycans on living cells by a chemoenzymatic glycoengineering approach.
AB - Structural glycobiology has traditionally been a challenging field due to a
limited set of tools available to investigate the diverse and complex glycan
molecules. However, we cannot ignore that glycans play critical roles in health
as well as in disease, and are present in more than 50% of all proteins and on
over 80% of all surface proteins. Chemoenzymatic glycoengineering (CGE) methods
are a powerful set of tools to synthesize complex glycans, but the full potential
of these methods have not been explored in cell biology yet. Herein, we report
the labeling of live Chinese hamster ovary (CHO) cells by employing three highly
specific glycosyltransferases: a sialyltransferase, a galactosyltransferase, and
an N-acetyl-glucosaminyl transferase. We verified our results by bio-orthogonal
blots and further rationalized them by computational modeling. We expect CGE
applications in cell biology to rise and their implementation will assist in
structural-functional discoveries in glycobiology. This research will contribute
to this effort.
PMID- 28500032
TI - Senescence gives insights into the morphogenetic evolution of anamniotes.
AB - Senescence represents a mechanism to avoid undesired cell proliferation that
plays a role in tumor suppression, wound healing and embryonic development. In
order to gain insight on the evolution of senescence, we looked at its presence
in developing axolotls (urodele amphibians) and in zebrafish (teleost fish),
which are both anamniotes. Our data indicate that cellular senescence is present
in various developing structures in axolotls (pronephros, olfactory epithelium of
nerve fascicles, lateral organs, gums) and in zebrafish (epithelium of the yolk
sac and in the lower part of the gut). Senescence was particularly associated
with transient structures (pronephros in axolotls and yolk sac in zebrafish)
suggesting that it may play a role in the elimination of these tissues. Our data
supports the notion that cellular senescence evolved early in vertebrate
evolution to influence embryonic development.
PMID- 28500034
TI - Primary pericardial mesothelioma and asbestos exposure: a rare fatal disease.
PMID- 28500033
TI - Proteomic responses to elevated ocean temperature in ovaries of the ascidian
Ciona intestinalis.
AB - Ciona intestinalis, a common sea squirt, exhibits lower reproductive success at
the upper extreme of the water temperatures it experiences in coastal New
England. In order to understand the changes in protein expression associated with
elevated temperatures, and possible response to global temperature change, we
reared C. intestinalis from embryos to adults at 18 degrees C (a temperature at
which they reproduce normally at our collection site in Rhode Island) and 22
degrees C (the upper end of the local temperature range). We then dissected
ovaries from animals at each temperature, extracted protein, and measured
proteomic levels using shotgun mass spectrometry (LC-MS/MS). 1532 proteins were
detected at a 1% false discovery rate present in both temperature groups by our
LC-MS/MS method. 62 of those proteins are considered up- or down-regulated
according to our statistical criteria. Principal component analysis shows a clear
distinction in protein expression pattern between the control (18 degrees C)
group and high temperature (22 degrees C) group. Similar to previous studies,
cytoskeletal and chaperone proteins are upregulated in the high temperature
group. Unexpectedly, we find evidence that proteolysis is downregulated at the
higher temperature. We propose a working model for the high temperature response
in C. intestinalis ovaries whereby increased temperature induces upregulation of
signal transduction pathways involving PTPN11 and CrkL, and activating
coordinated changes in the proteome especially in large lipid transport proteins,
cellular stress responses, cytoskeleton, and downregulation of energy metabolism.
PMID- 28500035
TI - Montgomery and informed consent: where are we now?
PMID- 28500036
TI - Heritability and risks associated with early onset hypertension:
multigenerational, prospective analysis in the Framingham Heart Study.
AB - Objective To determine the role of early onset versus late onset hypertension as
a risk factor for hypertension in offspring and cardiovascular death.Design
Multigenerational, prospective cohort study.Setting Framingham Heart
Study.Participants Two generations of community dwelling participants with blood
pressure measurements performed at serial examinations spanning six decades: 3614
first generation participants with mortality data and 1635 initially non
hypertensive second generation participants with data available on parental blood
pressure.Main outcome measures The main outcome measures were relation of
parental early onset hypertension (age <55 years) with incidence of hypertension
in offspring, using regression analyses, and relation of age at hypertension
onset with cause specific mortality using a case (cardiovascular death) versus
control (non-cardiovascular death) design.Results In second generation
participants, having one or both parents with late onset hypertension did not
increase the risk of hypertension compared with having parents with no
hypertension; by contrast, the hazard ratios of hypertension were 2.0 (95%
confidence interval 1.2 to 3.5) and 3.5 (1.9 to 6.1) in participants with one and
both parents with early onset hypertension, respectively. In first generation
decedents, 1151 cardiovascular deaths occurred (including 630 coronary deaths).
The odds of cardiovascular death increased linearly with decreasing age of
hypertension onset (P<0.001 for trend). Compared with non-hypertensive
participants, hypertension onset at age <45 years conferred an odds ratios of 2.2
(1.8 to 2.7) for cardiovascular death and 2.3 (1.8 to 2.9) for coronary death,
whereas hypertension onset at age >=65 years conferred a lower magnitude odds
ratios of 1.5 (1.2 to 1.9) for cardiovascular death and 1.4 (0.98 to 1.9) for
coronary death (P<=0.002 for differences in odds ratios between hypertension
onset at age <45 and age >=65).Conclusions Early onset and not late onset
hypertension in parents was strongly associated with hypertension in offspring.
In turn, early onset compared with late onset hypertension was associated with
greater odds of cardiovascular, and particularly coronary, death. These findings
suggest it may be important to distinguish between early onset and late onset
hypertension as a familial trait when assessing an individual's risk for
hypertension, and as a specific type of blood pressure trait when estimating risk
for cardiovascular outcomes in adults with established hypertension.
PMID- 28500037
TI - Improving Baculovirus Infectivity by Efficiently Embedding Enhancing Factors into
Occlusion Bodies.
AB - The relatively low infectivity of baculoviruses to their host larvae limits their
use as insecticidal agents on a larger scale. In the present study, a novel
strategy was developed to efficiently embed foreign proteins into Autographa
californica multiple nucleopolyhedrovirus (AcMNPV) occlusion bodies (OBs) to
achieve stable expression of foreign proteins and to improve viral infectivity. A
recombinant AcMNPV bacmid was constructed by expressing the 150-amino-acid (aa) N
terminal segment of polyhedrin under the control of the p10 promoter and the
remaining C-terminal 95-aa segment under the control of the polyhedrin promoter.
The recombinant virus formed OBs in Spodoptera frugiperda 9 cells, in which the
occlusion-derived viruses were embedded in a manner similar to that for wild-type
AcMNPV. Next, the 95-aa polyhedrin C terminus was fused to enhanced green
fluorescent protein, and the recombinant AcMNPV formed fluorescent green OBs and
was stably passaged in vitro and in vivo The AcMNPV recombinants were further
modified by fusing truncated Agrotis segetum granulovirus enhancin or truncated
Cydia pomonella granulovirus ORF13 (GP37) to the C-terminal 95 aa of polyhedrin,
and both recombinants were able to form normal OBs. Bioactivity assays indicated
that the median lethal concentrations of these two AcMNPV recombinants were 3- to
5-fold lower than that of the control virus. These results suggest that embedding
enhancing factors in baculovirus OBs by use of this novel technique may promote
efficient and stable foreign protein expression and significantly improve
baculovirus infectivity.IMPORTANCE Baculoviruses have been used as
bioinsecticides for over 40 years, but their relatively low infectivity to their
host larvae limits their use on a larger scale. It has been reported that it is
possible to improve baculovirus infectivity by packaging enhancing factors within
baculovirus occlusion bodies (OBs); however, so far, the packaging efficiency has
been low. In this article, we describe a novel strategy for efficiently embedding
foreign proteins into AcMNPV OBs by expressing N- and C-terminal (dimidiate)
polyhedrin fragments (150 and 95 amino acids, respectively) as fusions to foreign
proteins under the control of the p10 and polyhedrin promoters, respectively.
When this strategy was used to embed an enhancing factor (enhancin or GP37) into
the baculovirus OBs, 3- to 5-fold increases in baculoviral infectivity were
observed. This novel strategy has the potential to create an efficient protein
expression system and a highly efficient virus-based system for insecticide
production in the future.
PMID- 28500038
TI - Enrichment and Physiological Characterization of a Cold-Adapted Nitrite-Oxidizing
Nitrotoga sp. from an Eelgrass Sediment.
AB - Nitrite-oxidizing bacteria (NOB) are responsible for the second step of
nitrification in natural and engineered ecosystems. The recently discovered genus
Nitrotoga belongs to the Betaproteobacteria and potentially has high
environmental importance. Although environmental clones affiliated with Nitrotoga
are widely distributed, the limited number of cultivated Nitrotoga spp. results
in a poor understanding of their ecophysiological features. In this study, we
successfully enriched the nonmarine cold-adapted Nitrotoga sp. strain AM1 from
coastal sand in an eelgrass zone and investigated its physiological
characteristics. Multistep-enrichment approaches led to an increase in the
abundance of AM1 to approximately 80% of the total bacterial population. AM1 was
the only detectable NOB in the bacterial community. The 16S rRNA gene sequence of
AM1 was 99.6% identical to that of "Candidatus Nitrotoga arctica," which was
enriched from permafrost-affected soil. The highest nitrogen oxidation rate of
AM1 was observed at 16 degrees C. The half-saturation constant (Km ) and the
generation time were determined to be 25 MUM NO2- and 54 h, respectively. The
nitrite oxidation rate of AM1 was stimulated at concentrations of <30 mM NH4Cl
but completely inhibited at 50 mM NH4Cl. AM1 can grow well under specific
environmental conditions, such as low temperature and in the presence of a
relatively high concentration of free ammonia. These results help improve our
comprehension of the functional importance of NitrotogaIMPORTANCE Nitrite
oxidizing bacteria (NOB) are key players in the second step of nitrification,
which is an important process of the nitrogen cycle. Recent studies have
suggested that the organisms of the novel NOB genus Nitrotoga were widely
distributed and played a functional role in natural and engineered ecosystems.
However, only a few Nitrotoga enrichments have been obtained, and little is known
about their ecology and physiology. In this study, we successfully enriched a
Nitrotoga sp. from sand in a shallow coastal marine ecosystem and undertook a
physiological characterization. The laboratory experiments showed that the
Nitrotoga enrichment culture could adapt not only to low temperature but also to
relatively high concentrations of free ammonia. The determination of as-yet
unknown unique characteristics of Nitrotoga contributes to the improvement of our
insights into the microbiology of nitrification.
PMID- 28500039
TI - Selected Probiotic Lactobacilli Have the Capacity To Hydrolyze Gluten Peptides
during Simulated Gastrointestinal Digestion.
AB - The aim of this study was to demonstrate the capacity of probiotic lactobacilli
to hydrolyze immunogenic gluten peptides. Eighteen commercial strains of
probiotic lactobacilli with highly variable peptidase activity (i.e.,
aminopeptidase N, iminopeptidase, prolyl endopeptidyl peptidase, tripeptidase,
prolidase, prolinase, and dipeptidase), including toward Pro-rich peptides, were
tested in this study. Ten probiotic strains were selected on the basis of their
specific enzyme activity. When pooled, these 10 strains provided the peptidase
portfolio that is required to completely degrade the immunogenic gluten peptides
involved in celiac disease (CD). The selected probiotic mixture was able to
completely hydrolyze well-known immunogenic epitopes, including the gliadin 33
mer peptide, the peptide spanning residues 57 to 68 of the alpha9-gliadin (alpha9
gliadin peptide 57-68), A-gliadin peptide 62-75, and gamma-gliadin peptide 62-75.
During digestion under simulated gastrointestinal conditions, the pool of 10
selected probiotic lactobacilli strongly hydrolyzed the wheat bread gluten (ca.
18,000 ppm) to less than 10 ppm after 360 min of treatment. As determined by
multidimensional chromatography (MDLC) coupled to nanoelectrospray ionization
(nano-ESI)-tandem mass spectrometry (MS/MS), no known immunogenic peptides were
detected in wheat bread that was digested in the presence of the probiotics.
Accordingly, the level of cytokines (interleukin 2 [IL-2], IL-10, and interferon
gamma [IFN-gamma]) produced by duodenal biopsy specimens from CD patients who
consumed wheat bread digested by probiotics was similar to the baseline value
(negative control). Probiotics that specifically hydrolyze gluten polypeptides
could also be used to hydrolyze immunogenic peptides that contaminate gluten-free
products. This could provide a new and safe adjunctive therapy alternative to the
gluten-free diet (GFD).IMPORTANCE This study confirmed that probiotic
Lactobacillus strains have different enzymatic abilities for hydrolyzing
polypeptides, including the Pro-rich epitopes involved in the pathology of CD.
Ten lactobacilli with complementary peptidase activities that hydrolyze gluten
peptides during simulated gastrointestinal digestion were selected and tested.
The results collected showed the potential of probiotic formulas as novel dietary
treatments for CD patients.
PMID- 28500040
TI - Novel Sampling Method for Assessing Human-Pathogen Interactions in the Natural
Environment Using Boot Socks and Citizen Scientists, with Application to
Campylobacter Seasonality.
AB - This paper introduces a novel method for sampling pathogens in natural
environments. It uses fabric boot socks worn over walkers' shoes to allow the
collection of composite samples over large areas. Wide-area sampling is better
suited to studies focusing on human exposure to pathogens (e.g., recreational
walking). This sampling method is implemented using a citizen science approach:
groups of three walkers wearing boot socks undertook one of six routes, 40 times
over 16 months in the North West (NW) and East Anglian (EA) regions of England.
To validate this methodology, we report the successful implementation of this
citizen science approach, the observation that Campylobacter bacteria were
detected on 47% of boot socks, and the observation that multiple boot socks from
individual walks produced consistent results. The findings indicate higher
Campylobacter levels in the livestock-dominated NW than in EA (55.8% versus
38.6%). Seasonal differences in the presence of Campylobacter bacteria were found
between the regions, with indications of winter peaks in both regions but a
spring peak in the NW. The presence of Campylobacter bacteria on boot socks was
negatively associated with ambient temperature (P = 0.011) and positively
associated with precipitation (P < 0.001), results consistent with our
understanding of Campylobacter survival and the probability of material adhering
to boot socks. Campylobacter jejuni was the predominant species found;
Campylobacter coli was largely restricted to the livestock-dominated NW. Source
attribution analysis indicated that the potential source of C. jejuni was
predominantly sheep in the NW and wild birds in EA but did not differ between
peak and nonpeak periods of human incidence.IMPORTANCE There is debate in the
literature on the pathways through which pathogens are transferred from the
environment to humans. We report on the success of a novel method for sampling
human-pathogen interactions using boot socks and citizen science techniques,
which enable us to sample human-pathogen interactions that may occur through
visits to natural environments. This contrasts with traditional environmental
sampling, which is based on spot sampling techniques and does not sample human
pathogen interactions. Our methods are of practical value to scientists trying to
understand the transmission of pathogens from the environment to people. Our
findings provide insight into the risk of Campylobacter exposure from
recreational visits and an understanding of seasonal differences in risk and the
factors behind these patterns. We highlight the Campylobacter species
predominantly encountered and the potential sources of C. jejuni.
PMID- 28500041
TI - Real-Time PCR Method for Detection of Salmonella spp. in Environmental Samples.
AB - The methods currently used for detecting Salmonella in environmental samples
require 2 days to produce results and have limited sensitivity. Here, we describe
the development and validation of a real-time PCR Salmonella screening method
that produces results in 18 to 24 h. Primers and probes specific to the gene
invA, group D, and Salmonella enterica serovar Enteritidis organisms were
designed and evaluated for inclusivity and exclusivity using a panel of 329
Salmonella isolates representing 126 serovars and 22 non-Salmonella organisms.
The invA- and group D-specific sets identified all the isolates accurately. The
PCR method had 100% inclusivity and detected 1 to 2 copies of Salmonella DNA per
reaction. Primers specific for Salmonella-differentiating fragment 1 (Sdf-1) in
conjunction with the group D set had 100% inclusivity for 32 S Enteritidis
isolates and 100% exclusivity for the 297 non-Enteritidis Salmonella isolates.
Single-laboratory validation performed on 1,741 environmental samples
demonstrated that the PCR method detected 55% more positives than the Vitek
immunodiagnostic assay system (VIDAS) method. The PCR results correlated well
with the culture results, and the method did not report any false-negative
results. The receiver operating characteristic (ROC) analysis documented
excellent agreement between the results from the culture and PCR methods (area
under the curve, 0.90; 95% confidence interval of 0.76 to 1.0) confirming the
validity of the PCR method.IMPORTANCE This validated PCR method detects 55% more
positives for Salmonella in half the time required for the reference method,
VIDAS. The validated PCR method will help to strengthen public health efforts
through rapid screening of Salmonella spp. in environmental samples.
PMID- 28500042
TI - Carboxyl Analogue of Mutacin 1140, a Scaffold for Lead Antibacterial Discovery.
AB - Mutacin 1140 belongs to the epidermin group of lantibiotics. Epidermin class
lantibiotics are ribosomally synthesized and posttranslationally modified
antibiotics with potent activity against Gram-positive bacteria. In particular,
this class is effective at targeting drug-resistant Streptococcus pneumoniae,
methicillin-resistant Staphylococcus aureus (MRSA), Mycobacterium tuberculosis,
and Clostridium difficile A C-terminal S-[(Z)-2-aminovinyl]-d-cysteine (AviCys)
residue is derived from a decarboxylation of a terminal cysteine that is involved
in lanthionine ring formation. Studies on mutacin 1140 have revealed new insight
into the structural importance of the C-terminal AviCys residue. A C-terminal
carboxyl analogue of mutacin 1140 was engineered. Capping the C-terminal carboxyl
group with a primary amine restores bioactivity and affords a novel opportunity
to synthesize new analogues. A C-terminal fluorescein-labeled mutacin 1140
analogue traps lipid II into a large lipid II lantibiotic complex, similar to
that observed in vivo for the lantibiotic nisin. A C-terminal carboxyl analogue
of mutacin 1140 competitively inhibits the activity of native mutacin 1140 and
nisin. The presence of a C-terminal carboxyl group prevents the formation of the
large lipid II lantibiotic complexes but does not prevent the binding of the
lantibiotic to lipid II.IMPORTANCE This study addressed the importance of the C
terminal S-[(Z)-2-aminovinyl]-d-cysteine (AviCys) residue for antibacterial
activity. We have learned that the posttranslational modification for making the
AviCys residue is presumably important for the lateral assembly mechanism of
activity that traps lipid II into a large complex. The C-terminal carboxyl
analogue of this class of lantibiotics is agreeable to the addition of a wide
variety of substrates. The addition of fluorescein enabled in vivo visualization
of the epidermin class of lantibiotics in action. These results are significant
because, as we demonstrate, the presence of the AviCys residue is not essential
for bioactivity, but, more importantly, the removal of the carboxyl group is
essential. The ability to make a C-terminal carboxyl analogue that is modifiable
will facilitate the synthesis of novel analogues of the epidermin class of
lantibiotics that can be developed for new applications.
PMID- 28500043
TI - Potential for Waterborne and Invertebrate Transmission of West Nile Virus in the
Great Salt Lake, Utah.
AB - In November and December of 2013, a large mortality event involving 15,000 to
20,000 eared grebes (Podiceps nigricollis) occurred at the Great Salt Lake (GSL),
UT. The onset of the outbreak in grebes was followed by a mortality event in >86
bald eagles (Haliaeetus leucocephalus). During the die-off, West Nile virus (WNV)
was detected by reverse transcription-PCR (RT-PCR) or viral culture in the
carcasses of grebes and eagles submitted to the National Wildlife Health Center.
However, no activity of mosquitoes, the primary vectors of WNV, was detected by
the State of Utah's WNV monitoring program. The transmission of WNV has rarely
been reported during the winter in North America in the absence of known mosquito
activity; however, the size of this die-off, the habitat in which it occurred,
and the species involved are unique. We experimentally investigated whether WNV
could survive in water with a high salt content, as found at the GSL, and whether
brine shrimp, the primary food of migrating eared grebes on the GSL, could have
played a role in the transmission of WNV to feeding birds. We found that WNV can
survive up to 72 h at 4 degrees C in water containing 30 to 150 ppt NaCl, and
brine shrimp incubated with WNV in 30 ppt NaCl may adsorb WNV to their cuticle
and, through feeding, infect epithelial cells of their gut. Both mechanisms may
have potentiated the WNV die-off in migrating eared grebes on the GSL.IMPORTANCE
Following a major West Nile virus die-off of eared grebes and bald eagles at the
Great Salt Lake (GSL), UT, in November to December 2013, this study assessed the
survival of West Nile virus (WNV) in water as saline as that of the GSL and
whether brine shrimp, the major food for migrating grebes, could have played a
role as a vector for the virus. While mosquitoes are the major vector of WNV,
under certain circumstances, transmission may occur through contaminated water
and invertebrates as food.
PMID- 28500044
TI - RpoN (sigma54) Is Required for Floc Formation but Not for Extracellular
Polysaccharide Biosynthesis in a Floc-Forming Aquincola tertiaricarbonis Strain.
AB - Some bacteria are capable of forming flocs, in which bacterial cells become self
flocculated by secreted extracellular polysaccharides and other biopolymers. The
floc-forming bacteria play a central role in activated sludge, which has been
widely utilized for the treatment of municipal sewage and industrial wastewater.
Here, we use a floc-forming bacterium, Aquincolatertiaricarbonis RN12, as a model
to explore the biosynthesis of extracellular polysaccharides and the regulation
of floc formation. A large gene cluster for exopolysaccharide biosynthesis and a
gene encoding the alternative sigma factor RpoN1, one of the four paralogues,
have been identified in floc formation-deficient mutants generated by transposon
mutagenesis, and the gene functions have been further confirmed by genetic
complementation analyses. Interestingly, the biosynthesis of exopolysaccharides
remained in the rpoN1-disrupted flocculation-defective mutants, but most of the
exopolysaccharides were secreted and released rather than bound to the cells.
Furthermore, the expression of exopolysaccharide biosynthesis genes seemed not to
be regulated by RpoN1. Taken together, our results indicate that RpoN1 may play a
role in regulating the expression of a certain gene(s) involved in the self
flocculation of bacterial cells but not in the biosynthesis and secretion of
exopolysaccharides required for floc formation.IMPORTANCE Floc formation confers
bacterial resistance to predation of protozoa and plays a central role in the
widely used activated sludge process. In this study, we not only identified a
large gene cluster for biosynthesis of extracellular polysaccharides but also
identified four rpoN paralogues, one of which (rpoN1) is required for floc
formation in A. tertiaricarbonis RN12. In addition, this RpoN sigma factor
regulates the transcription of genes involved in biofilm formation and swarming
motility, as previously shown in other bacteria. However, this RpoN paralogue is
not required for the biosynthesis of exopolysaccharides, which are released and
dissolved into culture broth by the rpoN1 mutant rather than remaining tightly
bound to cells, as observed during the flocculation of the wild-type strain.
These results indicate that floc formation is a regulated complex process, and
other yet-to-be identified RpoN1-dependent factors are involved in self
flocculation of bacterial cells via exopolysaccharides and/or other biopolymers.
PMID- 28500045
TI - Sodium Lactate Negatively Regulates Shewanella putrefaciens CN32 Biofilm
Formation via a Three-Component Regulatory System (LrbS-LrbA-LrbR).
AB - The capability of biofilm formation has a major impact on the industrial and
biotechnological applications of Shewanella putrefaciens CN32. However, the
detailed regulatory mechanisms underlying biofilm formation in this strain remain
largely unknown. In the present report, we describe a three-component regulatory
system which negatively regulates the biofilm formation of S. putrefaciens CN32.
This system consists of a histidine kinase LrbS (Sputcn32_0303) and two cognate
response regulators, including a transcription factor, LrbA (Sputcn32_0304), and
a phosphodiesterase, LrbR (Sputcn32_0305). LrbS responds to the signal of the
carbon source sodium lactate and subsequently activates LrbA. The activated LrbA
then promotes the expression of lrbR, the gene for the other response regulator.
The bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) phosphodiesterase LrbR, containing
an EAL domain, decreases the concentration of intracellular c-di-GMP, thereby
negatively regulating biofilm formation. In summary, the carbon source sodium
lactate acts as a signal molecule that regulates biofilm formation via a three
component regulatory system (LrbS-LrbA-LrbR) in S. putrefaciens CN32.IMPORTANCE
Biofilm formation is a significant capability used by some bacteria to survive in
adverse environments. Numerous environmental factors can affect biofilm formation
through different signal transduction pathways. Carbon sources are critical
nutrients for bacterial growth, and their concentrations and types significantly
influence the biomass and structure of biofilms. However, knowledge about the
underlying mechanism of biofilm formation regulation by carbon source is still
limited. This work elucidates a modulation pattern of biofilm formation
negatively regulated by sodium lactate as a carbon source via a three-component
regulatory system in S. putrefaciens CN32, which may serve as a good example for
studying how the carbon sources impact biofilm development in other bacteria.
PMID- 28500046
TI - RoxB Is a Novel Type of Rubber Oxygenase That Combines Properties of Rubber
Oxygenase RoxA and Latex Clearing Protein (Lcp).
AB - Only two types of rubber oxygenases, rubber oxygenase (RoxA) and latex clearing
protein (Lcp), have been described so far. RoxA proteins (RoxAs) are c-type
cytochromes of ~70 kDa produced by Gram-negative rubber-degrading bacteria, and
they cleave polyisoprene into 12-oxo-4,8-dimethyltrideca-4,8-diene-1-al (ODTD), a
C15 oligo-isoprenoid, as the major end product. Lcps are common among Gram
positive rubber degraders and do not share amino acid sequence similarities with
RoxAs. Furthermore, Lcps have much smaller molecular masses (~40 kDa), are b-type
cytochromes, and cleave polyisoprene to a mixture of C20, C25, C30, and higher
oligo-isoprenoids as end products. In this article, we purified a new type of
rubber oxygenase, RoxB Xsp (RoxB of Xanthomonas sp. strain 35Y). RoxB Xsp is
distantly related to RoxAs and resembles RoxAs with respect to molecular mass
(70.3 kDa for mature protein) and cofactor content (2 c-type hemes). However,
RoxB Xsp differs from all currently known RoxAs in having a distinctive product
spectrum of C20, C25, C30, and higher oligo-isoprenoids that has been observed
only for Lcps so far. Purified RoxB Xsp revealed the highest specific activity of
4.5 U/mg (at 23 degrees C) of all currently known rubber oxygenases and exerts a
synergistic effect on the efficiency of polyisoprene cleavage by RoxA Xsp RoxB
homologs were identified in several other Gram-negative rubber-degrading species,
pointing to a prominent function of RoxB for the biodegradation of rubber in Gram
negative bacteria.IMPORTANCE The enzymatic cleavage of rubber (polyisoprene) is
of high environmental importance given that enormous amounts of rubber waste
materials are permanently released (e.g., by abrasion of tires). Research from
the last decade has discovered rubber oxygenase A, RoxA, and latex clearing
protein (Lcp) as being responsible for the primary enzymatic attack on the
hydrophobic and water-insoluble biopolymer poly(cis-1,4-isoprene) in Gram
negative and Gram-positive rubber-degrading bacteria, respectively. Here, we
provide evidence that a third type of rubber oxygenase is present in Gram
negative rubber-degrading species. Due to its characteristics, we suggest the
designation RoxB for the new type of rubber oxygenase. Bioinformatic analysis of
genome sequences indicates the presence of roxB homologs in other Gram-negative
rubber degraders.
PMID- 28500048
TI - Insight into the Recent Genome Duplication of the Halophilic Yeast Hortaea
werneckii: Combining an Improved Genome with Gene Expression and Chromatin
Structure.
AB - Extremophilic organisms demonstrate the flexibility and adaptability of basic
biological processes by highlighting how cell physiology adapts to environmental
extremes. Few eukaryotic extremophiles have been well studied and only a small
number are amenable to laboratory cultivation and manipulation. A detailed
characterization of the genome architecture of such organisms is important to
illuminate how they adapt to environmental stresses. One excellent example of a
fungal extremophile is the halophile Hortaea werneckii (Pezizomycotina,
Dothideomycetes, Capnodiales), a yeast-like fungus able to thrive at near
saturating concentrations of sodium chloride and which is also tolerant to both
UV irradiation and desiccation. Given its unique lifestyle and its remarkably
recent whole genome duplication, H. werneckii provides opportunities for testing
the role of genome duplications and adaptability to extreme environments. We
previously assembled the genome of H. werneckii using short-read sequencing
technology and found a remarkable degree of gene duplication. Technology
limitations, however, precluded high-confidence annotation of the entire genome.
We therefore revisited the H. wernickii genome using long-read, single-molecule
sequencing and provide an improved genome assembly which, combined with
transcriptome and nucleosome analysis, provides a useful resource for fungal
halophile genomics. Remarkably, the ~50 Mb H. wernickii genome contains 15,974
genes of which 95% (7608) are duplicates formed by a recent whole genome
duplication (WGD), with an average of 5% protein sequence divergence between
them. We found that the WGD is extraordinarily recent, and compared to
Saccharomyces cerevisiae, the majority of the genome's ohnologs have not diverged
at the level of gene expression of chromatin structure.
PMID- 28500047
TI - Self-reactive VH4-34-expressing IgG B cells recognize commensal bacteria.
AB - The germline immunoglobulin (Ig) variable heavy chain 4-34 (VH4-34) gene segment
encodes in humans intrinsically self-reactive antibodies that recognize I/i
carbohydrates expressed by erythrocytes with a specific motif in their framework
region 1 (FWR1). VH4-34-expressing clones are common in the naive B cell
repertoire but are rarely found in IgG memory B cells from healthy individuals.
In contrast, CD27+IgG+ B cells from patients genetically deficient for IRAK4 or
MYD88, which mediate the function of Toll-like receptors (TLRs) except TLR3,
contained VH4-34-expressing clones and showed decreased somatic hypermutation
frequencies. In addition, VH4-34-encoded IgGs from IRAK4- and MYD88-deficient
patients often displayed an unmutated FWR1 motif, revealing that these antibodies
still recognize I/i antigens, whereas their healthy donor counterparts harbored
FWR1 mutations abolishing self-reactivity. However, this paradoxical self
reactivity correlated with these VH4-34-encoded IgG clones binding commensal
bacteria antigens. Hence, B cells expressing germline-encoded self-reactive VH4
34 antibodies may represent an innate-like B cell population specialized in the
containment of commensal bacteria when gut barriers are breached.
PMID- 28500049
TI - Metabolic Adaptation to Nutrients Involves Coregulation of Gene Expression by the
RNA Helicase Dbp2 and the Cyc8 Corepressor in Saccharomyces cerevisiae.
AB - Cells fine-tune their metabolic programs according to nutrient availability in
order to maintain homeostasis. This is achieved largely through integrating
signaling pathways and the gene expression program, allowing cells to adapt to
nutritional change. Dbp2, a member of the DEAD-box RNA helicase family in
Saccharomyces cerevisiae, has been proposed to integrate gene expression with
cellular metabolism. Prior work from our laboratory has reported the necessity of
DBP2 in proper gene expression, particularly for genes involved in glucose
dependent regulation. Here, by comparing differentially expressed genes in dbp2?
to those of 700 other deletion strains from other studies, we find that CYC8 and
TUP1, which form a complex and inhibit transcription of numerous genes, corepress
a common set of genes with DBP2 Gene ontology (GO) annotations reveal that these
corepressed genes are related to cellular metabolism, including respiration,
gluconeogenesis, and alternative carbon-source utilization genes. Consistent with
a direct role in metabolic gene regulation, loss of either DBP2 or CYC8 results
in increased cellular respiration rates. Furthermore, we find that corepressed
genes have a propensity to be associated with overlapping long noncoding RNAs and
that upregulation of these genes in the absence of DBP2 correlates with decreased
binding of Cyc8 to these gene promoters. Taken together, this suggests that Dbp2
integrates nutrient availability with energy homeostasis by maintaining
repression of glucose-repressed, Cyc8-targeted genes across the genome.
PMID- 28500051
TI - Effects of the Ordering of Natural Selection and Population Regulation Mechanisms
on Wright-Fisher Models.
AB - We explore the effect of different mechanisms of natural selection on the
evolution of populations for one- and two-locus systems. We compare the effect of
viability and fecundity selection in the context of the Wright-Fisher model with
selection under the assumption of multiplicative fitness. We show that these two
modes of natural selection correspond to different orderings of the processes of
population regulation and natural selection in the Wright-Fisher model. We find
that under the Wright-Fisher model these two different orderings can affect the
distribution of trajectories of haplotype frequencies evolving with genetic
recombination. However, the difference in the distribution of trajectories is
only appreciable when the population is in significant linkage disequilibrium. We
find that as linkage disequilibrium decays the trajectories for the two different
models rapidly become indistinguishable. We discuss the significance of these
findings in terms of biological examples of viability and fecundity selection,
and speculate that the effect may be significant when factors such as gene
migration maintain a degree of linkage disequilibrium.
PMID- 28500050
TI - A Systemic Analysis of Transcriptomic and Epigenomic Data To Reveal Regulation
Patterns for Complex Disease.
AB - Integrating diverse genomics data can provide a global view of the complex
biological processes related to the human complex diseases. Although substantial
efforts have been made to integrate different omics data, there are at least
three challenges for multi-omics integration methods: (i) How to simultaneously
consider the effects of various genomic factors, since these factors jointly
influence the phenotypes; (ii) How to effectively incorporate the information
from publicly accessible databases and omics datasets to fully capture the
interactions among (epi)genomic factors from diverse omics data; and (iii) Until
present, the combination of more than two omics datasets has been poorly
explored. Current integration approaches are not sufficient to address all of
these challenges together. We proposed a novel integrative analysis framework by
incorporating sparse model, multivariate analysis, Gaussian graphical model, and
network analysis to address these three challenges simultaneously. Based on this
strategy, we performed a systemic analysis for glioblastoma multiforme (GBM)
integrating genome-wide gene expression, DNA methylation, and miRNA expression
data. We identified three regulatory modules of genomic factors associated with
GBM survival time and revealed a global regulatory pattern for GBM by combining
the three modules, with respect to the common regulatory factors. Our method can
not only identify disease-associated dysregulated genomic factors from different
omics, but more importantly, it can incorporate the information from publicly
accessible databases and omics datasets to infer a comprehensive interaction map
of all these dysregulated genomic factors. Our work represents an innovative
approach to enhance our understanding of molecular genomic mechanisms underlying
human complex diseases.
PMID- 28500052
TI - Exploring the Impact of Cleavage and Polyadenylation Factors on Pre-mRNA Splicing
Across Eukaryotes.
AB - In human, mouse, and Drosophila, the spliceosomal complex U1 snRNP (U1) protects
transcripts from premature cleavage and polyadenylation at proximal intronic
polyadenylation signals (PAS). These U1-mediated effects preserve transcription
integrity, and are known as telescripting. The watchtower role of U1 throughout
transcription is clear. What is less clear is whether cleavage and
polyadenylation factors (CPFs) are simply patrolled or if they might actively
antagonize U1 recruitment. In addressing this question, we found that, in the
introns of human, mouse, and Drosophila, and of 14 other eukaryotes, including
multi- and single-celled species, the conserved AATAAA PAS-a major target for
CPFs-is selected against. This selective pressure, approximated using DNA strand
asymmetry, is detected for peripheral and internal introns alike. Surprisingly,
it is more pronounced within-rather than outside-the action range of
telescripting, and particularly intense in the vicinity of weak 5' splice sites.
Our study uncovers a novel feature of eukaryotic genes: that the AATAAA PAS is
universally counter-selected in spliceosomal introns. This pattern implies that
CPFs may attempt to access introns at any time during transcription. However,
natural selection operates to minimize this access. By corroborating and
extending previous work, our study further indicates that CPF access to intronic
PASs might perturb the recruitment of U1 to the adjacent 5' splice sites. These
results open the possibility that CPFs may impact the splicing process across
eukaryotes.
PMID- 28500053
TI - Manipulating the Mitochondrial Genome To Enhance Cattle Embryo Development.
AB - The mixing of mitochondrial DNA (mtDNA) from the donor cell and the recipient
oocyte in embryos and offspring derived from somatic cell nuclear transfer (SCNT)
compromises genetic integrity and affects embryo development. We set out to
generate SCNT embryos that inherited their mtDNA from the recipient oocyte only,
as is the case following natural conception. While SCNT blastocysts produced from
Holstein (Bos taurus) fibroblasts depleted of their mtDNA, and oocytes derived
from Angus (Bos taurus) cattle possessed oocyte mtDNA only, the coexistence of
donor cell and oocyte mtDNA resulted in blastocysts derived from nondepleted
cells. Moreover, the use of the reprogramming agent, Trichostatin A (TSA),
further improved the development of embryos derived from depleted cells. RNA-seq
analysis highlighted 35 differentially expressed genes from the comparison
between blastocysts generated from nondepleted cells and blastocysts from
depleted cells, both in the presence of TSA. The only differences between these
two sets of embryos were the presence of donor cell mtDNA, and a significantly
higher mtDNA copy number for embryos derived from nondepleted cells. Furthermore,
the use of TSA on embryos derived from depleted cells positively modulated the
expression of CLDN8, TMEM38A, and FREM1, which affect embryonic development. In
conclusion, SCNT embryos produced by mtDNA depleted donor cells have the same
potential to develop to the blastocyst stage without the presumed damaging effect
resulting from the mixture of donor and recipient mtDNA.
PMID- 28500054
TI - Linkage Map of Lissotriton Newts Provides Insight into the Genetic Basis of
Reproductive Isolation.
AB - Linkage maps are widely used to investigate structure, function, and evolution of
genomes. In speciation research, maps facilitate the study of the genetic
architecture of reproductive isolation by allowing identification of genomic
regions underlying reduced fitness of hybrids. Here we present a linkage map for
European newts of the Lissotriton vulgaris species complex, constructed using two
families of F2 L. montandoni * L. vulgaris hybrids. The map consists of 1146
protein-coding genes on 12 linkage groups, equal to the haploid chromosome
number, with a total length of 1484 cM (1.29 cM per marker). It is notably
shorter than two other maps available for salamanders, but the differences in map
length are consistent with cytogenetic estimates of the number of chiasmata per
chromosomal arm. Thus, large salamander genomes do not necessarily translate into
long linkage maps, as previously suggested. Consequently, salamanders are an
excellent model to study evolutionary consequences of recombination rate
variation in taxa with large genomes and a similar number of chromosomes. A
complex pattern of transmission ratio distortion (TRD) was detected: TRD occurred
mostly in one family, in one breeding season, and was clustered in two genomic
segments. This is consistent with environment-dependent mortality of individuals
carrying L. montandoni alleles in these two segments and suggests a role of TRD
blocks in reproductive isolation. The reported linkage map will empower studies
on the genomic architecture of divergence and interactions between the genomes of
hybridizing newts.
PMID- 28500056
TI - A Pathway-Centered Analysis of Pig Domestication and Breeding in Eurasia.
AB - Ascertaining the molecular and physiological basis of domestication and breeding
is an active area of research. Due to the current wide distribution of its wild
ancestor, the wild boar, the pig (Sus scrofa) is an excellent model to study
these processes, which occurred independently in East Asia and Europe ca. 9000 yr
ago. Analyzing genome variability patterns in terms of metabolic pathways is
attractive since it considers the impact of interrelated functions of genes, in
contrast to genome-wide scans that treat genes or genome windows in isolation. To
that end, we studied 40 wild boars and 123 domestic pig genomes from Asia and
Europe when metabolic pathway was the unit of analysis. We computed statistical
significance for differentiation (Fst) and linkage disequilibrium (nSL)
statistics at the pathway level. In terms of Fst, we found 21 and 12 pathways
significantly differentiated at a q-value < 0.05 in Asia and Europe,
respectively; five were shared across continents. In Asia, we found six
significant pathways related to behavior, which involved essential
neurotransmitters like dopamine and serotonin. Several significant pathways were
interrelated and shared a variable percentage of genes. There were 12 genes
present in >10 significant pathways (in terms of Fst), comprising genes involved
in the transduction of a large number of signals, like phospholipase PCLB1, which
is expressed in the brain, or ITPR3, which has an important role in taste
transduction. In terms of nSL, significant pathways were mainly related to
reproductive performance (ovarian steroidogenesis), a similarly important target
trait during domestication and modern animal breeding. Different levels of
recombination cannot explain these results, since we found no correlation between
Fst and recombination rate. However, we did find an increased ratio of
deleterious mutations in domestic vs. wild populations, suggesting a relaxed
functional constraint associated with the domestication and breeding processes.
Purifying selection was, nevertheless, stronger in significantly differentiated
pathways than in random pathways, mainly in Europe. We conclude that pathway
analysis facilitates the biological interpretation of genome-wide studies.
Notably, in the case of pig, behavior played an important role, among other
physiological and developmental processes.
PMID- 28500055
TI - RNAi-Mediated Reverse Genetic Screen Identified Drosophila Chaperones Regulating
Eye and Neuromuscular Junction Morphology.
AB - Accumulation of toxic proteins in neurons has been linked with the onset of
neurodegenerative diseases, which in many cases are characterized by altered
neuronal function and synapse loss. Molecular chaperones help protein folding and
the resolubilization of unfolded proteins, thereby reducing the protein
aggregation stress. While most of the chaperones are expressed in neurons, their
functional relevance remains largely unknown. Here, using bioinformatics
analysis, we identified 95 Drosophila chaperones and classified them into seven
different classes. Ubiquitous actin5C-Gal4-mediated RNAi knockdown revealed that
~50% of the chaperones are essential in Drosophila Knocking down these genes in
eyes revealed that ~30% of the essential chaperones are crucial for eye
development. Using neuron-specific knockdown, immunocytochemistry, and robust
behavioral assays, we identified a new set of chaperones that play critical roles
in the regulation of Drosophila NMJ structural organization. Together, our data
present the first classification and comprehensive analysis of Drosophila
chaperones. Our screen identified a new set of chaperones that regulate eye and
NMJ morphogenesis. The outcome of the screen reported here provides a useful
resource for further elucidating the role of individual chaperones in Drosophila
eye morphogenesis and synaptic development.
PMID- 28500058
TI - Response to: 'HLA-A* 31:01 is not associated with the development of methotrexate
pneumonitis in the UK population: results from a genome wide association study'
by Bluett et al.
PMID- 28500057
TI - HLA-A 31:01 is not associated with the development of methotrexate pneumonitis in
the UK population: results from a genome-wide association study.
PMID- 28500059
TI - Toothpick impaction in a sigmoid diverticulum.
AB - A 70-year-old woman presented to our emergency department with recurrent episodes
of left lower quadrant pain. She subsequently underwent high anterior resection
with working diagnosis of acute diverticulitis, but intraoperatively was found to
have perforated sigmoid diverticulum due to toothpick impaction. A high index of
suspicion is required for diagnosis of toothpick ingestion. Appropriate
preoperative investigations such as endoscopy and CT, despite their fairly low
sensitivity, should be performed to increase the ability to accurately diagnose
this condition and therefore optimise subsequent management.
PMID- 28500060
TI - Unusual presentation of right coronary artery fistula.
PMID- 28500061
TI - Abdominal electroacupuncture demonstrates an increase in complete spontaneous
bowel movements.
PMID- 28500062
TI - Possible protective effect of prenatal omega-3 long-chain polyunsaturated fatty
acids supplementation on persistent wheeze and asthma in early childhood.
PMID- 28500063
TI - Oral antibiotics are as effective as intravenous antibiotics for postdischarge
treatment of complicated pneumonia in children.
PMID- 28500064
TI - Cry presence and amplitude do not reflect cortical processing of painful stimuli
in newborns with distinct responses to touch or cold.
AB - OBJECTIVE: Newborns requiring hospitalisation frequently undergo painful
procedures. Prevention of pain in infants is of prime concern because of adverse
associations with physiological and neurological development. However, pain
mitigation is currently guided by behavioural observation assessments that have
not been validated against direct evidence of pain processing in the brain. The
aim of this study was to determine whether cry presence or amplitude is a valid
indicator of pain processing in newborns. DESIGN: Prospective observational
cohort. SETTING: Newborn nursery. PATIENTS: Healthy infants born at >37 weeks and
<42 weeks gestation. INTERVENTIONS: We prospectively studied newborn cortical
responses to light touch, cold and heel stick, and the amplitude of associated
infant vocalisations using our previously published paradigms of time-locked
electroencephalogram (EEG) with simultaneous audio recordings. RESULTS: Latencies
of cortical peak responses to each of the three stimuli type were significantly
different from each other. Of 54 infants, 13 (24%), 19 (35%) and 35 (65%) had
cries in response to light touch, cold and heel stick, respectively. Cry in
response to non-painful stimuli did not predict cry in response to heel stick.
All infants with EEG data had measurable pain responses to heel stick, whether
they cried or not. There was no association between presence or amplitude of
cries and cortical nociceptive amplitudes. CONCLUSIONS: In newborns with distinct
brain responses to light touch, cold and pain, cry presence or amplitude
characteristics do not provide adequate behavioural markers of pain signalling in
the brain. New bedside assessments of newborn pain may need to be developed using
brain-based methodologies as benchmarks in order to provide optimal pain
mitigation.
PMID- 28500066
TI - Classic Spotlight, 1988 and 1989: Articles of Significant Interest Selected from
the Journal of Virology Archives by the Editors.
PMID- 28500068
TI - The first CT in a SAH: a picture tells a story.
AB - Finding the cause of acute neurological deterioration in the hours following
aneurysmal subarachnoid haemorrhage remains challenging. The presence of blood
casts in the ventricles proves that deterioration is secondary to acute
hydrocephalus and prompts immediate external ventricular drain placement.
PMID- 28500065
TI - Loss of Mpdz impairs ependymal cell integrity leading to perinatal-onset
hydrocephalus in mice.
AB - Hydrocephalus is a common congenital anomaly. LCAM1 and MPDZ (MUPP1) are the only
known human gene loci associated with non-syndromic hydrocephalus. To investigate
functions of the tight junction-associated protein Mpdz, we generated mouse
models. Global Mpdz gene deletion or conditional inactivation in Nestin-positive
cells led to formation of supratentorial hydrocephalus in the early postnatal
period. Blood vessels, epithelial cells of the choroid plexus, and cilia on
ependymal cells, which line the ventricular system, remained morphologically
intact in Mpdz-deficient brains. However, flow of cerebrospinal fluid through the
cerebral aqueduct was blocked from postnatal day 3 onward. Silencing of Mpdz
expression in cultured epithelial cells impaired barrier integrity, and loss of
Mpdz in astrocytes increased RhoA activity. In Mpdz-deficient mice, ependymal
cells had morphologically normal tight junctions, but expression of the
interacting planar cell polarity protein Pals1 was diminished and barrier
integrity got progressively lost. Ependymal denudation was accompanied by
reactive astrogliosis leading to aqueductal stenosis. This work provides a
relevant hydrocephalus mouse model and demonstrates that Mpdz is essential to
maintain integrity of the ependyma.
PMID- 28500070
TI - CXCR3.1 and CXCR3.2 Differentially Contribute to Macrophage Polarization in
Teleost Fish.
AB - The study of multiple copies of chemokine receptor genes in various teleosts has
long appealed to investigators seeking to understand the evolution of the immune
system. The CXCR CXCR3 gene has two isoforms, CXCR3.1 and CXCR3.2, which are both
expressed in macrophages. The distinct roles of teleost CXCR3s have not been
identified previously. In this article, we found that CXCR3.1 and CXCR3.2
differentially contributed to macrophage polarization in the teleosts: ayu
(Plecoglossus altivelis), grass carp (Ctenopharyngodon idella), and spotted green
pufferfish (Tetraodon nigroviridis). In ayu macrophages, the P. altivelis CXCR3.1
(PaCXCR3.1) gene was constitutively expressed, whereas the P. altivelis CXCR3.2
(PaCXCR3.2) gene was induced postinfection with Escherichia coli Upon E. coli
infection, PaCXCR3.1+ and PaCXCR3.2+ macrophages showed an M1 and an M2
phenotype, respectively. CXCL9-11-like proteins mediated M1 and M2 polarization
by interacting with the PaCXCR3.1 and PaCXCR3.2 proteins on macrophages,
respectively. The transcription factors P. altivelis STAT1 and P. altivelis STAT3
were activated in PaCXCR3.1+ and PaCXCR3.2+ macrophages, respectively.
Furthermore, the prognosis of septic ayu adoptively transferred with PaCXCR3.2+
macrophages was improved. Our data reveal a previously unknown mechanism for
macrophage polarization, suggesting that redundant genes may regulate crucial
functions in the teleost immune system.
PMID- 28500069
TI - B Cell Activity Is Impaired in Human and Mouse Obesity and Is Responsive to an
Essential Fatty Acid upon Murine Influenza Infection.
AB - Obesity is associated with increased risk for infections and poor responses to
vaccinations, which may be due to compromised B cell function. However, there is
limited information about the influence of obesity on B cell function and
underlying factors that modulate B cell responses. Therefore, we studied B cell
cytokine secretion and/or Ab production across obesity models. In obese humans, B
cell IL-6 secretion was lowered and IgM levels were elevated upon ex vivo anti
BCR/TLR9 stimulation. In murine obesity induced by a high fat diet, ex vivo IgM
and IgG were elevated with unstimulated B cells. Furthermore, the high fat diet
lowered bone marrow B cell frequency accompanied by diminished transcripts of
early lymphoid commitment markers. Murine B cell responses were subsequently
investigated upon influenza A/Puerto Rico/8/34 infection using a Western diet
model in the absence or presence of docosahexaenoic acid (DHA). DHA, an essential
fatty acid with immunomodulatory properties, was tested because its plasma levels
are lowered in obesity. Relative to controls, mice consuming the Western diet had
diminished Ab titers whereas the Western diet plus DHA improved titers.
Mechanistically, DHA did not directly target B cells to elevate Ab levels.
Instead, DHA increased the concentration of the downstream specialized
proresolving lipid mediators (SPMs) 14-hydroxydocosahexaenoic acid, 17
hydroxydocosahexaenoic acid, and protectin DX. All three SPMs were found to be
effective in elevating murine Ab levels upon influenza infection. Collectively,
the results demonstrate that B cell responses are impaired across human and mouse
obesity models and show that essential fatty acid status is a factor influencing
humoral immunity, potentially through an SPM-mediated mechanism.
PMID- 28500071
TI - Activated Microglia Desialylate and Phagocytose Cells via Neuraminidase, Galectin
3, and Mer Tyrosine Kinase.
AB - Activated microglia can phagocytose dying, stressed, or excess neurons and
synapses via the phagocytic receptor Mer tyrosine kinase (MerTK). Galectin-3 (Gal
3) can cross-link surface glycoproteins by binding galactose residues that are
normally hidden below terminal sialic acid residues. Gal-3 was recently reported
to opsonize cells via activating MerTK. We found that LPS-activated BV-2
microglia rapidly released Gal-3, which was blocked by calcineurin inhibitors.
Gal-3 bound to MerTK on microglia and to stressed PC12 (neuron-like) cells, and
it increased microglial phagocytosis of PC12 cells or primary neurons, which was
blocked by inhibition of MerTK. LPS-activated microglia exhibited a sialidase
activity that desialylated PC12 cells and could be inhibited by Tamiflu, a
neuraminidase (sialidase) inhibitor. Sialidase treatment of PC12 cells enabled
Gal-3 to bind and opsonize the live cells for phagocytosis by microglia. LPS
induced microglial phagocytosis of PC12 was prevented by small interfering RNA
knockdown of Gal-3 in microglia, lactose inhibition of Gal-3 binding, inhibition
of neuraminidase with Tamiflu, or inhibition of MerTK by UNC569. LPS-induced
phagocytosis of primary neurons by primary microglia was also blocked by
inhibition of MerTK. We conclude that activated microglia release Gal-3 and a
neuraminidase that desialylates microglial and PC12 surfaces, enabling Gal-3
binding to PC12 cells and their phagocytosis via MerTK. Thus, Gal-3 acts as an
opsonin of desialylated surfaces, and inflammatory loss of neurons or synapses
may potentially be blocked by inhibiting neuraminidases, Gal-3, or MerTK.
PMID- 28500072
TI - The Upregulation of Integrin alphaDbeta2 (CD11d/CD18) on Inflammatory Macrophages
Promotes Macrophage Retention in Vascular Lesions and Development of
Atherosclerosis.
AB - Macrophage accumulation is a critical step during development of chronic
inflammation, initiating progression of many devastating diseases. Leukocyte
specific integrin alphaDbeta2 (CD11d/CD18) is dramatically upregulated on
macrophages at inflammatory sites. Previously we found that CD11d overexpression
on cell surfaces inhibits in vitro cell migration due to excessive adhesion. In
this study, we have investigated how inflammation-mediated CD11d upregulation
contributes to macrophage retention at inflammatory sites during atherogenesis.
Atherosclerosis was evaluated in CD11d-/-/ApoE-/- mice after 16 wk on a Western
diet. CD11d deficiency led to a marked reduction in lipid deposition in aortas
and isolated macrophages. Macrophage numbers in aortic sinuses of CD11d-/- mice
were reduced without affecting their apoptosis and proliferation. Adoptive
transfer of fluorescently labeled wild-type and CD11d-/- monocytes into ApoE-/-
mice demonstrated similar recruitment from circulation, but reduced accumulation
of CD11d-/- macrophages within the aortas. Furthermore, CD11d expression was
significantly upregulated on macrophages in atherosclerotic lesions and M1
macrophages in vitro. Interestingly, expression of the related ligand-sharing
integrin CD11b was not altered. This difference defines their distinct roles in
the regulation of macrophage migration. CD11d-deficient M1 macrophages
demonstrated improved migration in a three-dimensional fibrin matrix and during
resolution of peritoneal inflammation, whereas migration of CD11b-/- M1
macrophages was not affected. These results prove the contribution of high
densities of CD11d to macrophage arrest during atherogenesis. Because high
expression of CD11d was detected in several inflammation-dependent diseases, we
suggest that CD11d/CD18 upregulation on proinflammatory macrophages may represent
a common mechanism for macrophage retention at inflammatory sites, thereby
promoting chronic inflammation and disease development.
PMID- 28500073
TI - FcgammaRIIIa Signaling Modulates Endosomal TLR Responses in Human CD4+ T Cells.
AB - Recognition of Ab-opsonized pathogens by immune cells triggers both TLR and Fc
receptor signaling. Fc receptors endocytose modified nucleic acids bound to Abs
and deliver them to endosomes, where they are recognized by nucleic acid-sensing
TLRs (NA-TLRs). We show that in CD4+ T cells, NA-TLRs, TLR3, TLR8, and TLR9 are
upregulated by FcgammaRIIIa-pSyk cosignaling and localize with FcgammaRIIIa on
the cell surface. TLR9 accumulates on the cell surface, where it recognizes CpG
oligonucleotide 2006. Subcellular location of NA-TLRs is a key determinant in
discriminating self versus viral nucleic acid. Hydroxychloroquine used for
treating systemic lupus erythematosus and a Syk inhibitor blocked NA-TLR
localization with FcgammaRIIIa. Engaging TLR9 with CpG oligonucleotide
contributes to the development of IL17A+ and IL-21+ populations. RNA-sequencing
analysis showed upregulation of proinflammatory cytokines, NF-kappaB signaling,
and heat shock protein pathway RNA transcripts. These data suggest a role for
FcgammaRIIIa-pSyk cosignaling in modulating NA-TLR responses in human CD4+ T
cells by affecting the amounts and cellular distribution. These events are
important for understanding of autoimmune pathology.
PMID- 28500075
TI - Overexpression of Human CD55 and CD59 or Treatment with Human CD55 Protects
against Renal Ischemia-Reperfusion Injury in Mice.
AB - Deficiency in the membrane-bound complement regulators CD55 and CD59 exacerbates
renal ischemia-reperfusion injury (IRI) in mouse models, but the effect of
increasing CD55 and CD59 activity has not been examined. In this study, we
investigated the impact of overexpression of human (h) CD55 +/- hCD59 or
treatment with soluble rhCD55 in a mouse model of renal IRI. Unilaterally
nephrectomised mice were subjected to 18 (mild IRI) or 22 min (moderate IRI) warm
renal ischemia, and analyzed 24 h after reperfusion for renal function (serum
creatinine and urea), complement deposition (C3b/c and C9), and infiltration of
neutrophils and macrophages. Transgenic mice expressing hCD55 alone were
protected against mild renal IRI, with reduced creatinine and urea levels
compared with wild type littermates. However, the renal function of the hCD55
mice was not preserved in the moderate IRI model, despite a reduction in C3b/c
and C9 deposition and innate cell infiltration. Mice expressing both hCD55 and
hCD59, on the other hand, were protected in the moderate IRI model, with
significant reductions in all parameters measured. Wild type mice treated with
rhCD55 immediately after reperfusion were also protected in the moderate IRI
model. Thus, manipulation of CD55 activity to increase inhibition of the C3 and
C5 convertases is protective against renal IRI, and the additional expression of
hCD59, which regulates the terminal complement pathway, provides further
protection. Therefore, anti-complement therapy using complement regulatory
proteins may provide a potential clinical option for preventing tissue and organ
damage in renal IRI.
PMID- 28500074
TI - Disease-Specific Effects of Matrix and Growth Factors on Adhesion and Migration
of Rheumatoid Synovial Fibroblasts.
AB - In rheumatoid arthritis (RA), cartilage and bone matrix are degraded, and
extracellular matrix (ECM) proteins, acting as cellular activators, are
liberated. Similar to ECM proteins, matrix-bound chemokines, cytokines, and
growth factors (GFs) influence functional properties of key cells in RA,
especially synovial fibroblasts. The role of these molecules on attachment,
migration, and proinflammatory and prodestructive activation of RASFs was
analyzed. Adhesion/migration of RASFs were examined under GF-enriched (GF+) or
reduced (GF-) conditions with or without addition of matrix-associated GFs, TGF
beta, and platelet-derived GF to GF- or culture supernatants. Fibroblast adhesion
and alterations in proinflammatory/prodestructive properties (e.g., IL-6/matrix
metalloproteinase 3-release) in response to matrix-associated molecules were
compared. Effects of GF+, GF-, and other ECM components on human RASF-mediated
cartilage invasion were examined in the SCID mouse model. RASF adhesion under GF-
conditions was significantly lower compared with GF+ conditions (6.8- versus 8.3
fold). This effect was specific for RA because control cells showed opposite
effects (e.g., osteoarthritis synovial fibroblasts [SF]; GF- versus GF+: 10.7-
versus 8-fold). Addition of TGF-beta to GF- increased RASF attachment (12.7-fold)
compared with other matrices and components. RASF adhesion to GF+ matrix resulted
in the strongest IL-6 and matrix metalloproteinase-3 release, and was even more
pronounced compared with supplementation of single GFs. In vivo, GF- matrix
decreased RASF-mediated cartilage invasion compared with GF+ matrix. ECM
components and especially GFs when bound within ECM actively enhance RASF
attraction and cartilage adhesion. This observation was specific for RASFs as a
reverse behavior was observed for controls.
PMID- 28500076
TI - Stat5 Is Required for CD103+ Dendritic Cell and Alveolar Macrophage Development
and Protection from Lung Injury.
AB - We tested the role of Stat5 in dendritic cell and alveolar macrophage (AM)
homeostasis in the lung using CD11c-cre mediated deletion (Cre+5f/f). We show
that Stat5 is required for CD103+ dendritic cell and AM development. We found
that fetal monocyte maturation into AMs was impaired in Cre+5f/f mice, and we
also confirmed impaired AM development of progenitor cells using mixed chimera
experiments. In the absence of Stat5 signaling in AMs, mice developed alveolar
proteinosis with altered lipid homeostasis. In addition, loss of Stat5 in CD11c+
cells was associated with exaggerated LPS-induced inflammatory responses and
vascular leak. In Cre+5f/f mice, there was loss of immune-dampening effects on
epithelial cells, a key source of CCL2 that serves to recruit monocytes and
macrophages. These findings demonstrate the critical importance of Stat5
signaling in maintaining lung homeostasis, and underscore the importance of
resident macrophages in moderating tissue damage and excess inflammation.
PMID- 28500077
TI - Alternative Start Sites Downstream of Non-Sense Mutations Drive Antigen
Presentation and Tolerance Induction to C-Terminal Epitopes.
AB - CTL responses to the transgene product remain an active area of concern for the
gene therapy field. A patient's underlying genetic mutation may influence the
qualitative nature of these potentially destructive T cell responses. Individuals
with a mutation that introduces a premature termination codon (PTC) that prevents
synthesis of the full-length peptide are considered more likely to mount a
transgene-specific T cell response because of a lack of immune tolerance to C
terminal epitopes as a consequence of absent endogenous Ag presentation. In this
article, we demonstrate that a human ornithine transcarbamylase gene containing
various PTC-inducing non-sense mutations is able to generate and present epitopes
downstream of the termination codon. Generation of these epitopes occurs
primarily from alternative translation start sites downstream of the stop codon.
Furthermore, we show that expression of these genes from adeno-associated virus
vectors in C57BL/6 mice is able to induce peripheral tolerance to epitopes
downstream of the PTC. These results suggest that, despite the lack of full
length endogenous protein, patients with PTC-inducing non-sense mutations may
still present T cell epitopes downstream of the premature termination site that
may render the subject tolerant to wild-type transgene products.
PMID- 28500079
TI - Exercise therapy for functional capacity in chronic diseases: an overview of meta
analyses of randomised controlled trials.
AB - OBJECTIVE: To summarise all meta-analyses of randomised controlled trials that
have evaluated the effects of exercise therapy on functional capacity in patients
with chronic diseases. DESIGN: Umbrella review of meta-analyses of randomised
controlled trials. DATA SOURCES: We systematically searched the CENTRAL, CINAHL,
DARE, Medline, OTSeeker, PEDro, SPORTDiscus, ProQuest Nursing & Allied Health
Database, Web of Science, Scopus, OpenGrey and BMC Proceedings from database
inception to 1 September 2016. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We
included meta-analyses that compared the effects of exercise therapy with no
treatment or usual care in adults with non-communicable chronic diseases and
included outcomes related to functional capacity. We excluded meta-analyses with
less than 100 patients. RESULTS: Eighty-five meta-analyses with 22 different
chronic diseases were included. The exercise interventions resulted in
statistically significant (p<0.05) improvements for 126 of 146 (86%) functional
capacity outcomes, compared with the control group. The standardised mean
differences were small in 64 (44%), moderate in 54 (37%) and large in 28 (19%) of
the 146 functional capacity outcomes. The results were similar for aerobic
exercise, resistance training, and aerobic and resistance training combined.
There were no significant differences in serious adverse effects between the
intervention and control groups in any of the meta-analyses. CONCLUSION: Exercise
therapy appears to be a safe way to improve functional capacity and reduce
disability in individuals with chronic disease.
PMID- 28500080
TI - Displaced middle-third clavicle fracture management in sport: still a challenge
in 2018. Should you call the surgeon to speed return to play?
PMID- 28500078
TI - A Time- and Compartment-Specific Activation of Lung Macrophages in Hypoxic
Pulmonary Hypertension.
AB - Studies in various animal models suggest an important role for pulmonary
macrophages in the pathogenesis of pulmonary hypertension (PH). Yet, the
molecular mechanisms characterizing the functional macrophage phenotype relative
to time and pulmonary localization and compartmentalization remain largely
unknown. In this study, we used a hypoxic murine model of PH in combination with
FACS to quantify and isolate lung macrophages from two compartments over time and
characterize their programing via RNA sequencing approaches. In response to
hypoxia, we found an early increase in macrophage number that was restricted to
the interstitial/perivascular compartment, without recruitment of macrophages to
the alveolar compartment or changes in the number of resident alveolar
macrophages. Principal component analysis demonstrated significant differences in
overall gene expression between alveolar and interstitial macrophages (IMs) at
baseline and after 4 and 14 d hypoxic exposure. Alveolar macrophages at both day
4 and 14 and IMs at day 4 shared a conserved hypoxia program characterized by
mitochondrial dysfunction, proinflammatory gene activation, and mTORC1 signaling,
whereas IMs at day 14 demonstrated a unique anti-inflammatory/proreparative
programming state. We conclude that the pathogenesis of vascular remodeling in
hypoxic PH involves an early compartment-independent activation of lung
macrophages toward a conserved hypoxia program, with the development of
compartment-specific programs later in the course of the disease. Thus,
harnessing time- and compartment-specific differences in lung macrophage
polarization needs to be considered in the therapeutic targeting of macrophages
in hypoxic PH and potentially other inflammatory lung diseases.
PMID- 28500081
TI - Quadriceps strengthening with and without blood flow restriction in the treatment
of patellofemoral pain: a double-blind randomised trial.
AB - BACKGROUND: Quadriceps strengthening exercises are part of the treatment of
patellofemoral pain (PFP), but the heavy resistance exercises may aggravate knee
pain. Blood flow restriction (BFR) training may provide a low-load quadriceps
strengthening method to treat PFP. METHODS: Seventy-nine participants were
randomly allocated to a standardised quadriceps strengthening (standard) or low
load BFR. Both groups performed 8 weeks of leg press and leg extension, the
standard group at 70% of 1 repetition maximum (1RM) and the BFR group at 30% of
1RM. Interventions were compared using repeated-measures analysis of variance for
Kujala Patellofemoral Score, Visual Analogue Scale for 'worst pain' and 'pain
with daily activity', isometric knee extensor torque (Newton metre) and
quadriceps muscle thickness (cm). Subgroup analyses were performed on those
participants with painful resisted knee extension at 60 degrees . RESULTS: Sixty
nine participants (87%) completed the study (standard, n=34; BFR, n=35). The BFR
group had a 93% greater reduction in pain with activities of daily living
(p=0.02) than the standard group. Participants with painful resisted knee
extension (n=39) had greater increases in knee extensor torque with BFR than
standard (p<0.01). No between-group differences were found for change in Kujala
Patellofemoral Score (p=0.31), worst pain (p=0.24), knee extensor torque (p=0.07)
or quadriceps thickness (p=0.2). No difference was found between interventions at
6 months. CONCLUSION: Compared with standard quadriceps strengthening, low load
with BFR produced greater reduction in pain with daily living at 8 weeks in
people with PFP. Improvements were similar between groups in worst pain and
Kujala score. The subgroup with painful resisted knee extension had larger
improvements in quadriceps strength from BFR. TRIAL REGISTRATION NUMBER:
12614001164684.
PMID- 28500085
TI - The most common vices of men can damage fertility and the health of the next
generation.
AB - Animal and human studies demonstrate that acquired paternal traits can impair
both a male's fertility and the health of his offspring, including advanced age,
smoking, stress, trauma, under-nutrition, infection, toxin exposure, and obesity.
Many of these factors lead to similar changes to neurological, behavioural,
and/or metabolic functioning in offspring. The molecular mechanisms that both
respond to the paternal environment and act to transmit traits to offspring are
beginning to emerge. This review focuses on three vices of men (alcohol
consumption, overweight/obesity, and tobacco smoking) that damage fertility and
pose risks to offspring health. These vices are not only the three most prevalent
but are also leading risk factors for death and disability adjusted life years
(DALYs) worldwide. Moreover, given that these vices are predominantly self
inflicted, interventions aimed at mitigating their consequences are readily
identified.
PMID- 28500083
TI - Hepatic thyroid signaling of heat-stressed late pregnant and early lactating
cows.
AB - During the transition between late gestation and early lactation, dairy cows
experience severe metabolic stress due to the high energy and nutrient
requirements of the fetus and the mammary gland. Additional thermal stress that
occurs with rising temperatures during the ongoing climate change has further
adverse implications on energy intake, metabolism and welfare. The thyroid
hormone (TH)-mediated cellular signaling has a pivotal role in regulation of body
temperature, energy intake and metabolic adaptation to heat. To distinguish
between energy intake and heat stress-related effects, Holstein cows were first
kept at thermoneutrality at 15 degrees C followed by exposure to heat stress (HS)
at 28 degrees C or pair-feeding (PF) at 15 degrees C for 6 days, in late
pregnancy and again in early lactation. Herein, we focused on hepatic metabolic
changes associated with alterations in the hypothalamic-pituitary-thyroid axis in
HS and PF animals. T3 and T4 levels dropped with HS or PF; however, in HS
animals, this decline was more pronounced. Thyroid-stimulating hormone (TSH)
levels remain unaffected, while plasma cholesterol concentrations were lower in
HS than PF animals. Hepatic marker genes for TH action (THRA, DIO1 and PPARGC1)
decreased after HS and were lower compared to PF cows but only post-partum.
Proteomics data revealed reduced hepatic amino acid catabolism ante-partum and a
shift toward activated beta-oxidation and gluconeogenesis but declined oxidative
stress defense post-partum. Thus, liver metabolism of HS and PF cows adapts
differently to diminished energy intake both ante-partum and post-partum, and a
different TH sensitivity is involved in the regulation of catabolic processes.
PMID- 28500084
TI - Bisphenol A promotes hepatic lipid deposition involving Kupffer cells M1
polarization in male mice.
AB - Bisphenol A (BPA), one of the most common environmental endocrine disruptors, is
considered to promote hepatic lipid deposition. However, the mechanism has not
been fully elucidated. The polarization of Kupffer cells (KCs) plays an important
role in hepatic inflammation by promoting pro-inflammatory M1 phenotype (M1KCs),
which contributes to dysregulated lipid metabolism. The purpose of this study is
to investigate the role of KC polarization in BPA-induced hepatosteatosis in male
mice. In this study, we examined hepatic lipid contents and quantified M1KC in
BPA-treated CD1 mice, and further explored the interaction between KCs and
hepatocytes using conditional HepG2 cell culture. BPA treatment significantly
increased hepatic fat contents in CD1 mice, accompanied by increased number of
pro-inflammatory M1KCs and enhanced secretion of inflammatory cytokines.
Increased lipid contents were also observed in HepG2 cells treated with BPA.
Interestingly, higher TG contents were observed in HepaG2 cells treated with
conditional media from BPA-treated KCs, compared with those treated with BPA
directly. Incubation of KCs with BPA promoted the polarization of KCs to pro
inflammatory M1 dominant subtypes, which was blocked by estrogen antagonist
ICI182780. Taken together, our results revealed that M1KCs polarization is
involved in BPA-induced hepatic fat deposition, which is possibly associated with
the estrogen receptor signaling pathway.
PMID- 28500086
TI - Detection of pneumothoraces in patients with multiple blunt trauma: use and
limitations of eFAST.
AB - BACKGROUND: Extended focused assessment with sonography for trauma (eFAST) has
been shown to have moderate sensitivity for detection of pneumothorax in trauma.
Little is known about the location or size of missed pneumothoraces or clinical
predictors of pneumothoraces in patients with false-negative eFAST. METHODS: This
retrospective cross-sectional study includes all patients with multiple blunt
trauma diagnosed with pneumothorax who underwent both eFAST and CT performed in
the ED of a level 1 trauma centre in Switzerland between 1 June 2012 and 30
September 2014. Sensitivity of eFAST for pneumothorax was determined using CT as
the gold standard. Demographic and clinical characteristics of those who had a
pneumothorax detected by eFAST and those who did not were compared using the Mann
Whitney U or Pearson's chi2 tests. Univariate binary logistic regression models
were used to identify predictors for pneumothoraces in patients with negative
eFAST examination. RESULTS: The study included 109 patients. Overall sensitivity
for pneumothorax on eFAST was 0.59 and 0.81 for pneumothoraces requiring
treatment. Compared with those detected by eFAST, missed pneumothoraces were less
likely to be ventral (30 (47.6%) vs 4 (9.3%), p <0.001) and more likely to be
apical and basal (7 (11.1%) vs 15 (34.9%), p=0.003; 11 (17.5%) vs 18 (41.9%),
p=0.008, respectively). The missed pneumothoraces were smaller than the detected
pneumothoraces (left side: 30.7+/-17.4 vs 12.1+/-13.9 mm; right side: 30.2+/-10.1
vs 6.9+/-10.2 mm, both p <0.001). No clinical variables were identified which
predicted pneumothoraces in falsely negative eFAST. Among those pneumothoraces
missed by eFAST, 30% required tube thoracostomy compared with 88.9% of those
detected with eFAST. CONCLUSION: In our study, pneumothoraces missed by eFAST
were smaller and in atypical locations compared with those detected by eFAST and
needed thoracic drainage less often.
PMID- 28500088
TI - Spotting the black swan: why emergency medicine is ahead of the curve.
AB - "Black Swans", originally described as an economic theory, are unexpected events
whose potential to occur only becomes apparent after they have happened. The
concept is very relevant to the practice of Emergency Medicine and this article
explores how black swans impact on emergency care and how staff unconsciously aim
to mitigate against them.
PMID- 28500087
TI - Feasibility of the Manchester Acute Coronary Syndromes (MACS) decision rule to
safely reduce unnecessary hospital admissions: a pilot randomised controlled
trial.
AB - BACKGROUND: Observational studies suggest that the Manchester Acute Coronary
Syndromes (MACS) decision rule can effectively 'rule out' and 'rule in' acute
coronary syndromes (ACS) following a single blood test. In a pilot randomised
controlled trial, we aimed to determine whether a large trial is feasible.
METHODS: Patients presenting to two EDs with suspected cardiac chest pain were
randomised to receive care guided by the MACS decision rule (intervention group)
or standard care (controls). The primary efficacy outcome was a successful
discharge from the ED, defined as a decision to discharge within 4 hours of
arrival providing that the patient did not have a missed acute myocardial
infarction (AMI) or develop a major adverse cardiac event (MACE: death, AMI or
coronary revascularisation) within 30 days. Feasibility outcomes included
recruitment and attrition rates. RESULTS: In total, 138 patients were included
between October 2013 and October 2014, of whom 131 (95%) were randomised (66 to
intervention and 65 controls). Nine (7%) patients had prevalent AMI and six (5%)
had incident MACE within 30 days. All 131 patients completed 30-day follow-up and
were included in the final analysis with no missing data for the primary
analyses. Compared with standard care, a significantly greater proportion of
patients whose care was guided by the MACS rule were successfully discharged
within 4 hours (26% vs 8%, adjusted OR 5.45, 95% CI 1.73 to 17.11, p=0.004). No
patients in either group who were discharged within 4 hours had a diagnosis of
AMI or incident MACE within 30 days (0.0%, 95% CI 0% to 20.0% in the intervention
group). CONCLUSIONS: In this pilot trial, use of the MACS rule led to a
significant increase in safe discharges from the ED but a larger, fully powered
trial remains necessary. Our findings seem to support the feasibility of that
trial. TRIAL REGISTRATION NUMBER: ISRCTN 86818215. RESEARCH ETHICS COMMITTEE
REFERENCE: 13/NW/0081. UKCRN REGISTRATION ID: 14334.
PMID- 28500089
TI - An exploration of patients' experiences of participation in a randomised
controlled trial of the Manchester Acute Coronary Syndromes (MACS) decision rule.
AB - BACKGROUND: As an important part of a pilot study to determine the feasibility of
a large randomised controlled trial (RCT) comparing use of the Manchester Acute
Coronary Syndromes (MACS) decision rule with standard care, we aimed to explore
patient attitudes and potential barriers to participation in a trial of this
nature. METHODS: We conducted a qualitative study nested within a pilot RCT
comparing use of the MACS rule (which could enable some patients with chest pain
to be discharged earlier) with standard care. Semi-structured interviews with
consenting participants were conducted with reference to a bespoke topic guide.
Interviews were audio recorded, transcribed verbatim and analysed using the
Framework method with an inductive approach. RESULTS: The 10 interviewees
expressed that participation in the trial was generally acceptable. All but one
recommended participation to others. Participants who were in pain or anxious at
the time of arrival reported that the initial invitation to participate in the
trial was sometimes made too early. The approach was welcome, providing they had
been given time to settle. Interviewees welcomed the opportunity that trial
participation offered for them to play a more active role in their healthcare and
to reduce unnecessary waiting time. Participants appeared to like the fact that
participation in the trial might mean they could return home sooner and welcomed
the provision of follow-up. Although several participants described being
generally sceptical of medical research, they were amenable to participation in
this trial. This appears to be because they agreed with the need for research in
this field and perceived the intervention as non-invasive. CONCLUSIONS: Patients
were positive about their participation in this RCT comparing the MACS rule with
standard care. A number of areas for improving trial design were identified and
should be considered in the planning of future large trials. TRIAL REGISTRATION:
ISRCTN 86818215 RESEARCH ETHICS COMMITTEE REFERENCE: 13/NW/0081 UKCRN
REGISTRATION ID: 14334.
PMID- 28500090
TI - Effect of Facility IAC-Accreditation on CT Dose Awareness and Reduction.
AB - PURPOSE: To assess characteristics of computed tomography (CT) facilities
accredited by the Intersocietal Accreditation Commission (IAC) and evaluate the
perceived effect of accreditation on CT radiation dose awareness and reduction.
METHODS: IAC-accredited CT facilities were sent a survey in April 2016, which
included 20 questions categorized into 5 groups: equipment and facility (7),
patient safety/practice (5), protocols (2), dose reduction practice (3), and
quality improvement (3). RESULTS: The response rate was 20.7% (N = 607). A
majority of facilities (80%) reported that radiation dose was adjusted based on
patient size. Before undergoing accreditation, 79% of facilities reported annual
review of CT protocols and radiation exposure. Following accreditation, that
number increased to 93%. A majority (77%) of respondents indicated that the
accreditation process, along with the IAC Standards and Guidelines, increased
awareness of radiation exposure; in addition, 36% indicated that radiation doses
were lower after undertaking accreditation. DISCUSSION: This study demonstrated
that most IAC-accredited facilities followed recommended radiation safety
practices by adjusting radiation dose based on patient size, reviewing protocols
annually, and participating in quality improvement activities that focus on
patient radiation exposure. CONCLUSION: IAC-accredited facilities reported that
the accreditation process had a positive effect on radiation dose awareness and
reduced dose associated with CT examinations.
PMID- 28500091
TI - Forensic Age Estimation Using the Medial Clavicular Epiphysis: A Study Review.
AB - PURPOSE: To discuss current literature evaluating the medial clavicular epiphysis
to assess an individual's age using various imaging modalities. METHODS: Four
scholarly research databases were searched to find studies that examined living
subjects. Several articles were included that used cadavers, and a textbook was
used to detail the anatomy of the clavicle. Thirty-nine articles were analyzed.
RESULTS: The literature indicated that several imaging modalities, including
conventional radiography, computed tomography, magnetic resonance, and
sonography, are being used to evaluate the medial clavicular epiphysis to
estimate an individual's age in the forensic context. In addition to multiple
modalities, researchers are using various staging classification systems, ethnic
groups, and interpreter criteria to establish reference data. DISCUSSION: There
is a need to determine the age of individuals involved in civil and criminal
proceedings who do not have valid birth date documentation. The clavicle is the
last bone in the human body to complete fusion. The clavicle begins to fuse in
the early teens and completes medial epiphyseal fusion in the late 20s. Clavicle
fusion spans the legally significant age range of 18 through 21. Multiple
variables influence the final age estimation, including interpreters' experience,
the individual's socioeconomic class or area of origin, and limitations within
the imaging modalities. CONCLUSION: Computed tomography is the modality of choice
for forensic age estimation using the medial clavicular epiphysis. Radiologic
technologists should be cognizant of current forensic age estimation practices,
and future research should continue to provide reference data to improve accuracy
of age estimation in those individuals who lack documentation of their date of
birth.
PMID- 28500092
TI - Patient-centered Radiation Safety.
AB - Some suggest radiation safety is evolving from a provider-centered process to a
more patient-centered approach. This shift places additional responsibility on
radiologic technologists to educate patients about the possible risks and
benefits of medical radiation exposure so patients can be equal partners in their
care. This article discusses the ethics of radiation protection and the
development of the patient-centered approach, and the radiologic technologist's
role in ensuring patient-centered radiation safety is addressed.
PMID- 28500094
TI - Recent News.
PMID- 28500093
TI - Vertebral Osteomyelitis and the Role of Imaging.
AB - Vertebral osteomyelitis is a rare but serious infectious disease that causes
inflammation and destruction of the spinal vertebrae. Prompt diagnosis and
treatment are essential to avoid adverse outcomes. This article reviews risk
factors for vertebral osteomyelitis, disease mechanisms, signs and symptoms, and
diagnostic criteria. Medical imaging techniques for vertebral osteomyelitis are a
main focus, and treatment, prognosis, and possible complications also are
discussed. Finally, the special case of pediatric patients with vertebral
osteomyelitis is presented.
PMID- 28500097
TI - Data Analysis: Closing the Loop in Assessment.
PMID- 28500098
TI - Student Reflections on Clinical: Lessons Learned.
PMID- 28500099
TI - TeamSTEPPS: Addressing Imaging Procedure Appropriateness.
PMID- 28500100
TI - EQUIP: Enhancing Quality Using the Inspection Program.
PMID- 28500102
TI - Using Social Media and Hashtags to Engage Medical Imaging Students.
PMID- 28500101
TI - Flamingo Stress View of the Pelvis.
PMID- 28500104
TI - Technical Factors and Exposure Indicators.
PMID- 28500106
TI - Medical 3-D Printing.
AB - Three-dimensional printing is used in the manufacturing industry, medical and
pharmaceutical research, drug production, clinical medicine, and dentistry, with
implications for precision and personalized medicine. This technology is
advancing the development of patient-specific prosthetics, stents, splints, and
fixation devices and is changing medical education, treatment decision making,
and surgical planning. Diagnostic imaging modalities play a fundamental role in
the creation of 3-D printed models. Although most 3-D printed objects are rigid,
flexible soft-tissue-like prosthetics also can be produced.
PMID- 28500107
TI - Metastatic Breast Cancer.
AB - Despite advances in breast cancer screening, diagnosis, and treatment, nearly 12%
of patients with a diagnosis of breast cancer eventually develop metastatic
disease, or breast cancer that has spread beyond the breast to other parts of the
body. No cure for metastatic breast cancer yet exists, and it is associated with
a poor prognosis: The 5-year survival rate is 26%. Nevertheless, many treatments
can improve and extend the lives of patients with metastatic breast cancer. This
article reviews the types of breast cancer and cancer staging systems. It also
discusses the molecular subtypes of breast cancer, symptoms of metastatic breast
cancer, and current treatments for the disease.
PMID- 28500108
TI - Recent News.
PMID- 28500110
TI - Bilateral brachial rhabdomyolysis caused by push-up exercise.
PMID- 28500109
TI - Hemifacial spasm and neurovascular compression syndrome.
PMID- 28500111
TI - Migration of a Nexplanon contraceptive implant to the pulmonary artery.
AB - This is a case report of a 17-year-old woman who experienced distant
intravascular migration of a radio-opaque Nexplanon contraceptive implant. She
presented with an impalpable implant and this was located using CT in the left
lower lobe pulmonary artery. Significant migration of a contraceptive implant is
an uncommon risk. Using radio-opaque contraceptive implants such as Nexplanon
increases the ability to locate them if migration occurs.
PMID- 28500112
TI - Intra-abdominal inflammatory myofibroblastic tumour (IMT) mimicking gonadal mass
in a male infant with undescended testes.
AB - Inflammatory myofibroblastic tumour (IMT) is a rare benign neoplastic tumour,
originally described as an inflammatory pseudotumor. Only a single case of IMT in
the spermatic cord associated with undescended testes has been reported. We
present a rare case of abdominal IMT in a male infant with undescended bilateral
testes. The abdominopelvic mass was suspected to be a gonadal malignancy due to
empty scrotal sac but proved to be otherwise on histopathology. Mass was
completely resected and orchiopexy was performed for both undescended normal
appearing testes. The patient developed a recurrent mass 2 months later involving
the left spermatic cord and the left testicle. Radical surgery was performed with
removal of the left testicle and spermatic cord. The patient was disease-free at
1-year follow-up.
PMID- 28500113
TI - Annular pancreas causing duodenal obstruction in an adult.
PMID- 28500114
TI - Pseudoprogression in lung adenocarcinoma during treatment with nivolumab.
PMID- 28500115
TI - Erroneously elevated glucose values due to maltose interference in mutant glucose
dehydrogenase pyrroloquinolinequinone (mutant GDH-PQQ) based glucometer.
AB - Currently available glucose test strip enzymes include glucose oxidase (GOD) and
glucose dehydrogenase (GDH). In GDH-based glucometers, glucose oxidation can be
catalysed by different cofactors: nicotinamide adenine dinucleotide (GDH-NAD),
flavin adenine dinucleotide (GDH-FAD), pyrroloquinolinequinone (GDH-PQQ) and
mutant GDH-PQQ. GOD-based and GDH-NAD-based glucometers are substrate-specific
and do not react with sugars other than glucose. GDH-FAD reacts with xylose only
in addition to glucose. GDH-PQQ is not glucose-specific; in addition to glucose,
it reacts with different other sugars and produces falsely high values of
capillary glucose in the presence of such substances. There are reports of
several deaths associated with usage of GDH-PQQ-based test strips. A modified
form of GDH-PQQ, the so-called mutant GDH-PQQ, is supposedly free from such
interferences. In this article spuriously high glucose values due to maltose
interference in a glucometer using the mutant GDH-PQQ chemistry are being
reported.
PMID- 28500116
TI - A 53-year-old man with dyspnoea, respiratory failure, consistent with infliximab
induced acute interstitial pneumonitis after an accelerated induction dosing
schedule.
AB - A 53-year-old man with ulcerative colitis (UC) suffered fatal acute interstitial
pneumonitis (AIP) post completing an accelerated infliximab induction course.
This is the first case reported in this setting. A literature review found four
similar cases of infliximab-induced interstitial lung disease in the setting of
treating patients with UC using standard infliximab regimens had successful
treatment of the subjects post infliximab discontinuation. Unfortunately, the
patient we are presenting, who had an accelerated infliximab induction course,
did not survive. Although a prior small trial along more recent new small studies
continue to show a benefit in reducing the need for early colectomy with the
accelerated infliximab induction regimen as salvage therapy, it should be used
cautiously until more safety data are available. Further larger trials are
required to investigate rare side effects that may be associated with this
regimen such as rapidly progressive lung toxicity as seen in this patient.
PMID- 28500117
TI - Intracranial hypotension causing pituitary enlargement.
PMID- 28500118
TI - Isolated prostate cancer soft tissue recurrence 10 years after radical
prostatectomy.
AB - In advanced disease, prostate cancer is well known to invade locally as well as
metastasise to distant locations. Metastases occur commonly in lymph nodes and
bone but have also been known to involve certain visceral organs, particularly
the lungs. Involvement of soft tissue by metastases is far less common,
particularly in the context of cancer recurrence. We present the case of a male
aged 68 years who presented with a rising prostate-specific antigen (PSA) 10
years after radical prostatectomy (RP). The PSA increased despite salvage
radiotherapy and was ultimately found to be caused by a PSA secreting prostate
cancer soft tissue mass in the suprapubic region. Surgical resection of the mass
caused a sharp decline in the PSA to negligible levels. This case highlights the
need for ongoing surveillance post-RP and the potential for prostate cancer
recurrence in the soft tissue that is refractory to routine salvage radiotherapy.
PMID- 28500119
TI - Evaluating the pictorial warnings on tobacco products in Arabian Gulf countries
against other international pictorial warnings.
AB - BACKGROUND: Few assessments of pictorial warnings (PWs) on cigarette packs
implemented in Gulf Cooperation Council (GCC) countries have been done. METHODS:
This article includes two cross-sectional studies. In Study 1, convenience
samples of adults from the Kingdom of Saudi Arabia (n=111) and USA (n=115)
participated in a consumer survey to rate a total of nine PWs from the GCC,
Australia and the UK. Outcome measures were affective responses to PWs and
concerns about smoking. In Study 2, tobacco control experts (n=14) from multiple
countries rated the same PWs on a potential efficacy scale and completed one open
ended question about each. The PWs were altered to mask their country of origin.
Analyses compared ranking on multiple outcomes and examined ratings by country of
origin and by smoking status. RESULTS: In the consumer survey, participants from
both countries rated the PWs from GCC lower than PWs from other countries on the
two measures. The mixed-model analysis showed significant differences between the
PWs from Australia and those from the GCC and between the PWs from the UK and
those from the GCC (p<0.001) in the consumer and expert samples. The experts'
comments about the PWs implemented in the GCC were negative overall and confirmed
previously identified themes about effective PWs. CONCLUSION: This study shows
PWs originating from the GCC had significantly lower ratings than those
implemented in Australia and the UK. The GCC countries may need to re-evaluate
the currently implemented PWs and update them periodically.
PMID- 28500120
TI - The clinical conundrum of diagnosing and treating systemic sarcoidosis in a high
TB burden area.
AB - A 53-year-old woman from Southern India presented with weight loss, anorexia,
fever and asthenia. Whole body positron emission tomography/computed tomography
(PET-CT) showed fluorodeoxyglucose-avid mediastinal and abdominal lymphadenopathy
with hepatic, splenic, parotid and lacrimal glandular inflammations. Endoscopic
ultrasound-guided fine needle aspiration of subcarinal lymph node showed non
caseating granulomas. Initial serum ACE level was elevated but with normal
calcium. Despite the suspicion of sarcoidosis, a trial of antituberculosis
therapy was started empirically due to similar presentations of disseminated
tuberculosis (TB) in this high endemic area. The patient subsequently
deteriorated and was admitted with symptomatic hypercalcaemia. Her subsequent ACE
levels were very high, supportive of a diagnosis of systemic sarcoidosis. She was
given steroid pulse therapy, and 5 months later had fully recovered. This case
highlights the challenges faced by physicians in high TB-endemic areas when
managing granulomatous diseases as they are concerned about missing TB, the
difficulties in diagnosing sarcoidosis and the role of pulse steroid therapy.
PMID- 28500121
TI - Angioleiomyoma of the upper lip.
AB - This report describes a case of labial angioleiomyoma in a 52-year-old woman. The
patient had noticed a slow-growing painless isolated mass in her upper lip for 6
months. The mass was surgically excised, and pathological examination was
consistent with angioleiomyoma. Surgical excision was curative, and there was no
recurrence at 12-month follow-up.
PMID- 28500122
TI - Navigating the benefits and burdens of life-saving treatment in severely
decompensated cirrhosis: an illustrative, multisourced narrative.
AB - Severely decompensated cirrhosis presents major challenges in terms of balancing
the benefits and burdens of life-extending treatment. Using accounts and
interviews with a patient, her mother, consultant hepatologists and a consultant
intensivist, this article explores the decision making around a 43-year-old woman
with alcoholic liver disease who died after 100 days in a hospital. Particular
focus is given to decisions on escalation, recognition of futility, distress
associated with therapy and how messages given during end-of-life discussions are
processed. Without suggesting that the case is an example of ideal practice, the
importance of frequent multidisciplinary discussion, clinical re-evaluation and
continuity of care is emphasised.
PMID- 28500123
TI - Enterococcus casseliflavus septicaemia associated with hepatobiliary infection in
a 75-year-old man.
AB - Enterococcus casseliflavus is a rare non-faecium, non-faecalis, vancomycin
resistant enterococcus (VRE) that is responsible for up to 2% of all enterococcal
infections. Septicaemia with this bacterium is usually seen in older patients
with multiple comorbidities who have had several previous hospitalisations.
Septicaemia with E. casseliflavus portends a poorer prognosis, and treatment
usually involves administration of antienterococcal beta-lactams or anti-VRE
medications such as linezolid or daptomycin. We present such a case of a 75-year
old man who developed E. casseliflavus septicaemia of presumably hepatobiliary
origin and responded well to treatment with intravenous beta-lactams.
PMID- 28500124
TI - Unusual cause of mediastinal mass.
PMID- 28500125
TI - Acute urinary retention and constipation precipitated by herpes zoster infection.
AB - A 76-year-old man presented to the emergency department complaining of acute
urinary retention (AUR) and severe constipation. His recent medical history
included 4 days of treatment in the community for gluteal herpes zoster with
famciclovir. A transurethral catheter was passed and the patient completed a full
course of famciclovir with resolution of constipation. The patient's catheter was
successfully removed 3 weeks after his presentation. We report on the clinical
presentation and management of an unusual case of AUR and constipation caused by
a zoster viral infection of the S2-S4 dermatome.
PMID- 28500126
TI - Lemierre's syndrome; a rare cause of septic arthritis.
AB - Lemierre's syndrome is a rare condition characterised by pharyngitis leading to
septic thrombophlebitis of the internal jugular vein. Complications include
pulmonary septic emboli, septic arthritis and disseminated intravascular
coagulation. The authors present a case of a healthy woman aged 25 years with
septic arthritis of the shoulder due to this unusual cause. This diagnosis was
made via a combination of clinical, radiological and microbiological findings. It
was successfully treated via surgical and antimicrobial interventions. The
patient made a good recovery with minimal associated morbidity or loss of
function. This case highlights the importance for awareness and high index of
suspicion for rarer causes of septic arthritis in young healthy adults as early
appropriate intervention maximises prognosis.
PMID- 28500127
TI - The efficacy of hyperbaric oxygen therapy in the treatment of central retinal
artery occlusion.
AB - Central retinal artery occlusion (CRAO) is an ophthalmological emergency. Various
treatment modalities have been tried, but none have shown to alter natural
history of the disease. Hyperoxia can restore retinal oxygenation, and favourable
results were obtained with hyperbaric oxygen therapy (HBOT). We report two
patients with sudden visual loss due to CRAO treated with HBOT. Case 1: a 61-year
old female, presented with CRAO in her left eye(OS). She was submitted to eight
sessions of HBOT(2.4atmosphere absolute (ATA)). BCVA(Best corrected visual
acuity) improved from counting fingers (CF) to 1.0 and fluorescein angiography
(FA) showed a normalisation. Vascular study showed a value of 8.8% for HbA1c and
ventricular extrasystoles. Case 2: a 69-year-old male presented with CRAO in his
OS. Nine sessions of HBOT(2.4 ATA) were performed. Best corrected visual acuity
(BCVA)improved from CF to 0.8 and the FA was normalised. Vascular study revealed
an atheromatous carotid disease, and cardiac pathology. HBOT seems to be
beneficial on the recovery of vision following CRAO.
PMID- 28500128
TI - Retroperitoneal schwannoma: an unusual cause of abdominal distention.
PMID- 28500129
TI - Terminal ileal lymphoma resembling abdominal abscess.
PMID- 28500130
TI - A seizure-induced T8 burst fracture re-presenting as an acute abdomen.
AB - A male aged 44 years presented to the emergency department with a 1-week history
of intermittent right-sided abdominal pain radiating to the midline. Examination
demonstrated a tender right upper quadrant with voluntary guarding and a low
grade fever. One week previously, he had been admitted to hospital after an
isolated, self-terminating seizure secondary to an deliberate venlafaxine
overdose. His upper abdominal symptoms started immediately postseizure but at the
time were attributed to musculoskeletal chest pain by the discharging team. Acute
cholecystitis was suspected, but liver function tests, amylase and an erect chest
radiograph were unremarkable.The abdominal pain responded well to morphine,
permitting a thorough reassessment of the patient, which revealed midthoracic
spine tenderness, previously undetected. Prior to this, the patient had not
complained of any back pain. A CT scan confirmed a burst fracture of T8 requiring
urgent transfer to the local spinal unit for posterior stabilisation.
PMID- 28500131
TI - Cerebral venous sinus thrombosis during superselective intra-arterial infusion of
cisplatin and concomitant radiotherapy for maxillary squamous cell carcinoma.
PMID- 28500132
TI - The zinc finger E-box-binding homeobox 1 (Zeb1) promotes the conversion of mouse
fibroblasts into functional neurons.
AB - The zinc finger E-box-binding transcription factor Zeb1 plays a pivotal role in
the epithelial-mesenchymal transition. Numerous studies have focused on the
molecular mechanisms by which Zeb1 contributes to this process. However, the
functions of Zeb1 beyond the epithelial-mesenchymal transition remain largely
elusive. Using a transdifferentiation system to convert mouse embryonic
fibroblasts (MEFs) into functional neurons via the neuronal transcription factors
achaete-scute family bHLH (basic helix-loop-helix) transcription factor1 (Ascl1),
POU class 3 homeobox 2 (POU3F2/Brn2), and neurogenin 2 (Neurog2, Ngn2) (ABN), we
found that Zeb1 was up-regulated during the early stages of transdifferentiation.
Knocking down Zeb1 dramatically attenuated the transdifferentiation efficiency,
whereas Zeb1 overexpression obviously increased the efficiency of
transdifferentiation from MEFs to neurons. Interestingly, Zeb1 improved the
transdifferentiation efficiency induced by even a single transcription factor
(e.g. Asc1 or Ngn2). Zeb1 also rapidly promoted the maturation of induced neuron
cells to functional neurons and improved the formation of neuronal patterns and
electrophysiological characteristics. Induced neuron cells could form functional
synapse in vivo after transplantation. Genome-wide RNA arrays showed that Zeb1
overexpression up-regulated the expression of neuron-specific genes and down
regulated the expression of epithelial-specific genes during conversion. Taken
together, our results reveal a new role for Zeb1 in the transdifferentiation of
MEFs into neurons.
PMID- 28500133
TI - The heme-regulatory motif of nuclear receptor Rev-erbbeta is a key mediator of
heme and redox signaling in circadian rhythm maintenance and metabolism.
AB - Rev-erbbeta is a heme-responsive transcription factor that regulates genes
involved in circadian rhythm maintenance and metabolism, effectively bridging
these critical cellular processes. Heme binding to Rev-erbbeta indirectly
facilitates its interaction with the nuclear receptor co-repressor (NCoR1),
resulting in repression of Rev-erbbeta target genes. Fe3+-heme binds in a 6
coordinate complex with axial His and Cys ligands, the latter provided by a heme
regulatory motif (HRM). Rev-erbbeta was thought to be a heme sensor based on a
weak Kd value for the Rev-erbbeta.heme complex of 2 MUm determined with
isothermal titration calorimetry. However, our group demonstrated with UV-visible
difference titrations that the Kd value is in the low nanomolar range, and the
Fe3+-heme off-rate is on the order of 10-6 s-1 making Rev-erbbeta ineffective as
a sensor of Fe3+-heme. In this study, we dissected the kinetics of heme binding
to Rev-erbbeta and provided a Kd for Fe3+-heme of ~0.1 nm Loss of the HRM axial
thiolate via redox processes, including oxidation to a disulfide with a
neighboring cysteine or dissociation upon reduction of Fe3+- to Fe2+-heme,
decreased binding affinity by >20-fold. Furthermore, as measured in a co
immunoprecipitation assay, substitution of the His or Cys heme ligands in Rev
erbbeta was accompanied by a significant loss of NCoR1 binding. These results
demonstrate the importance of the Rev-erbbeta HRM in regulating interactions with
heme and NCoR1 and advance our understanding of how signaling through HRMs
affects the major cellular processes of circadian rhythm maintenance and
metabolism.
PMID- 28500134
TI - The E3 ubiquitin ligase WWP2 facilitates RUNX2 protein transactivation in a mono
ubiquitination manner during osteogenic differentiation.
AB - Poly-ubiquitination-mediated RUNX2 degradation is an important cause of age- and
inflammation-related bone loss. NEDD4 family E3 ubiquitin protein ligases are
thought to be the major regulators of RUNX2 poly-ubiquitination. However, we
observed a mono-ubiquitination of RUNX2 that was catalyzed by WWP2, a member of
the NEDD4 family of E3 ubiquitin ligases. WWP2 has been reported to catalyze the
mono-ubiquitination of Goosecoid in chondrocytes, facilitating craniofacial
skeleton development. In this study, we found that osteogenic differentiation of
mesenchymal stem cells promoted WWP2 expression and nuclear accumulation.
Knockdown of Wwp2 in mesenchymal stem cells and osteoblasts led to significant
deficiencies of osteogenesis, including decreased mineral deposition and down
regulation of osteogenic marker genes. Co-immunoprecipitation experiments showed
the interaction of WWP2 with RUNX2 in vitro and in vivo Mono-ubiquitination by
WWP2 leads to RUNX2 transactivation, as evidenced by the wild type of WWP2, but
not its ubiquitin ligase-dead mutant, augmenting RUNX2-reponsive reporter
activity. Moreover, deletion of WWP2-dependent mono-ubiquitination resulted in
striking defects of RUNX2 osteoblastic activity. In addition, ectopic expression
of the constitutively active type 1A bone morphogenetic protein receptor enhanced
WWP2-dependent RUNX2 ubiquitination and transactivation, demonstrating a
regulatory role of bone morphogenetic protein signaling in the WWP2-RUNX2 axis.
Taken together, our results provide evidence that WWP2 serves as a positive
regulator of osteogenesis by augmenting RUNX2 transactivation in a non
proteolytic mono-ubiquitination manner.
PMID- 28500135
TI - Dual Antiplatelet Therapy Continuation Beyond 1 Year After Drug-Eluting Stents: A
Meta-Analysis of Randomized Trials.
AB - BACKGROUND: The benefits and harms of dual antiplatelet therapy (DAPT)
continuation beyond 1 year after drug-eluting stent implantation as compared with
1-year DAPT remain controversial. METHODS AND RESULTS: We searched for randomized
trials that compared longer than 1-year DAPT versus 1-year DAPT after drug
eluting stenting. A meta-analysis was performed by using standard frequentist and
random-effects Bayesian approaches. Four trials comprising 17 650 participants
were included. Compared with 1-year DAPT, extended DAPT did not affect all-cause
mortality (odds ratio [OR], 1.11; 95% confidence interval [CI], 0.79-1.5; P=0.53)
or cardiovascular mortality (OR, 1.03; 95% CI, 0.72-1.46; P=0.88). Extended DAPT
was associated with a reduction in the risk of myocardial infarction (OR, 0.56;
95% CI, 0.43-0.73; P<0.001), nonsignificant reductions of stent thrombosis (OR,
0.46; 95% CI, 0.16-1.27; P=0.13), similar risk of stroke (OR, 0.91; 95% CI, 0.65
1.26; P=0.56), and an increased risk of major bleeding (OR, 1.49; 95% CI, 1.06
2.11; P=0.02). By using Bayesian meta-analysis, we found moderate evidence of a
reduction of myocardial infarction (OR, 0.62; 95% credible intervals, 0.39-1.05)
and weak evidence of an increase in major bleeding (OR, 1.66; 95% credible
intervals, 0.89-3.09) associated with extended DAPT. CONCLUSIONS: In this meta
analysis, extended DAPT beyond 1 year prevented myocardial infarctions and
increased major bleedings, but the strength of evidence for these effects was not
strong. DAPT continuation beyond 1 year showed no effects on mortality.
PMID- 28500136
TI - Percutaneous Mechanical Circulatory Support Devices in Cardiogenic Shock.
AB - Despite a high rate of early revascularization and use of intra-aortic balloon
pump counterpulsation therapy, the prognosis of patients with cardiogenic shock
has remained poor. In the hopes of improving outcomes, clinicians are
increasingly turning to percutaneous left and right mechanical circulatory
support devices. Until recently, the evidence base for these devices had
consisted only of observational data, meta-analyses, and small feasibility
trials. In this article, we describe the contemporary outcomes of patients with
cardiogenic shock, the hemodynamics of cardiogenic shock, and hemodynamic effects
of percutaneous mechanical circulatory support devices. We then use this
discussion to provide clinicians with a useful framework for understanding when
selecting between or while managing patients with a percutaneous mechanical
circulatory support devices. We critically review the recently published data for
and against the use of commercially available devices-the intra-aortic balloon
pump counterpulsation, the Impella system, the TandemHeart, and venous-arterial
extracorporeal membrane oxygenation-and highlight gaps in our understanding.
Given such gaps, a consensus multidisciplinary approach that combines expertise
from interventional cardiologists, heart failure specialists, cardiac surgeons,
and cardiac anesthesiologists may help pair the right patient with the right
device at the right time.
PMID- 28500137
TI - Outcomes After Decompression of the Right Ventricle in Infants With Pulmonary
Atresia With Intact Ventricular Septum Are Associated With Degree of Tricuspid
Regurgitation: Results From the Congenital Catheterization Research
Collaborative.
AB - BACKGROUND: Outcomes after right ventricle (RV) decompression in infants with
pulmonary atresia with intact ventricular septum vary widely. Descriptions of
outcomes are limited to small single-center studies. METHODS AND RESULTS:
Neonates undergoing RV decompression for pulmonary atresia with intact
ventricular septum were included from 4 pediatric centers. Primary end point was
reintervention post-RV decompression; secondary end points included circulation
type at latest follow-up. Ninety-nine patients (71 with pulmonary atresia with
intact ventricular septum and 28 with virtual atresia) underwent RV decompression
at median 3 (25th-75th, 2-5) days of age. Seventy-one patients (72%) underwent at
least 1 reintervention after decompression. Median duration of follow-up was 3
years (range, 1-10). Freedom from reintervention was 51% at 1 month and 23% at 3
years. In multivariable analysis, reintervention was associated with virtual
atresia (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.28-091;
P=0.027), smaller RV length (HR, 0.94; 95% CI, 0.89-0.99; P=0.027), and <=mild
tricuspid regurgitation (TR; HR, 3.58; 95% CI, 2.04-6.30; P<0.001). Patients
undergoing surgical shunt or ductal stent were less likely to have virtual
atresia (HR, 0.36; 95% CI, 0.15-0.85; P=0.02) and more likely to have higher RV
end-diastolic pressure (HR, 1.07; 95% CI, 1.00-1.15; P=0.057) and <=mild TR (HR,
3.50; 95% CI, 1.75-7.0; P<0.001). Number of reinterventions was associated with
<=mild TR (rate ratio, 1.87; 95% CI, 1.23-2.87; P=0.0037). Multivariable analysis
indicated that <2-ventricle circulation status was associated with <=mild TR
(odds ratio, 18.6; 95% CI, 5.3-65.2; P<0.001) and lower RV area (odds ratio,
0.81; 95% CI, 0.72-0.91; P<0.001). CONCLUSIONS: Patients with pulmonary atresia
with intact ventricular septum deemed suitable for RV decompression have a high
reintervention burden although most achieve 2-ventricle circulation. TR <=mild at
baseline is strongly associated with reintervention and <2-ventricle circulation
at medium-term follow-up. Degree of baseline TR may be an important marker of
long-term outcomes in this population.
PMID- 28500140
TI - Therapeutic Management of Low-Gradient Aortic Stenosis: First Assess the State of
the Schrodinger Cat Before Making a Decision.
PMID- 28500138
TI - Legacy Effect of Coronary Perforation Complicating Percutaneous Coronary
Intervention for Chronic Total Occlusive Disease: An Analysis of 26 807 Cases
From the British Cardiovascular Intervention Society Database.
AB - BACKGROUND: Coronary perforation (CP) during chronic total occlusion percutaneous
coronary intervention for stable angina (CTO-PCI) is a rare but serious event.
The evidence base is limited, and the long-term effects are unclear. Using a
national PCI database, the incidence, predictors, and outcomes of CP during CTO
PCI were defined. METHODS AND RESULTS: Data analyzed from the British
Cardiovascular Intervention Society data set on all CTO-PCI procedures performed
in England and Wales between 2006 and 2013. Multivariate logistic regressions and
propensity scores were used to identify predictors of CP and its association with
outcomes. A total of 376 CP were recorded from 26 807 CTO-PCI interventions
(incidence of 1.40%) with an increase in frequency during the study period
(P=0.012). Patient-related factors associated with an increased risk of CP were
age and female sex. Procedural factors indicative of complex CTO intervention
strongly related to an increased risk of CP with a close relationship between the
number of complex strategies used and CP evident (P=0.008 for trend). Tamponade
occurred in 16.6% and emergency surgery in 3.4% of cases. Adverse outcomes were
frequent in those patients with perforation including bleeding, transfusion,
myocardial infarction, and death. A legacy effect of perforation on mortality was
evident, with an odds ratio for 12-month mortality of 1.60 for perforation
survivors compared with matched nonperforation survivors without a CP (P<0.0001).
CONCLUSIONS: Many of the factors associated with an increased risk of CP were
related to CTO complexity. Perforation was associated with adverse outcomes, with
a legacy effect on later mortality after CP also observed.
PMID- 28500139
TI - High- Versus Low-Gradient Severe Aortic Stenosis: Demographics, Clinical
Outcomes, and Effects of the Initial Aortic Valve Replacement Strategy on Long
Term Prognosis.
AB - BACKGROUND: There is considerable debate on the management of patients with low
gradient severe aortic stenosis (LG-AS), defined as aortic valve area <1 cm2 with
peak aortic jet velocity <=4.0 m/s, and mean aortic pressure gradient <=40 mm Hg.
METHODS AND RESULTS: In the CURRENT AS registry (Contemporary Outcomes After
Surgery and Medical Treatment in Patients With Severe Aortic Stenosis), there
were 2097 patients (initial aortic valve replacement [AVR] strategy: n=977, and
conservative strategy: n=1120) with high-gradient severe aortic stenosis (HG-AS)
and 1712 patients (initial AVR strategy: n=219, and conservative strategy:
n=1493) with LG-AS. AVR was more frequently performed in HG-AS patients than in
LG-AS patients (60% versus 28%) during the entire follow-up. In the comparison
between the initial AVR and conservative groups, the propensity score-matched
cohorts were developed in both HG-AS (n=887 for each group) and LG-AS (n=218 for
each group) strata. The initial AVR strategy when compared with the conservative
strategy was associated with markedly lower risk for a composite of aortic valve
related death or heart failure hospitalization in both HG-AS and LG-AS strata
(hazard ratio, 0.30; 95% confidence interval, 0.25-0.37; P<0.001 and hazard
ratio, 0.46; 95% confidence interval, 0.32-0.67; P<0.001, respectively). Among
1358 patients with LG-AS with preserved left ventricular ejection fraction, the
initial AVR strategy was associated with a better outcome than the conservative
strategy (adjusted hazard ratio, 0.37; 95% confidence interval, 0.23-0.59;
P<0.001). CONCLUSIONS: The initial AVR strategy was associated with better
outcomes than the conservative strategy in both HG-AS and LG-AS patients,
although AVR was less frequently performed in LG-AS patients than in HG-AS
patients. The favorable effect of initial AVR strategy was also seen in patients
with LG-AS with preserved left ventricular ejection fraction. CLINICAL TRIAL
REGISTRATION: URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier:
UMIN000012140.
PMID- 28500145
TI - Where are all the vet nurses?
PMID- 28500146
TI - Reviewing Schedule 3: why now and what might the outcome be?
AB - Liz Cox, chair of the RCVS VN Council and the Schedule 3 Working Party, explains
more about the RCVS's review of Schedule 3.
PMID- 28500141
TI - Chronic obstructive pulmonary disease in Scottish military veterans.
AB - INTRODUCTION: Smoking is a major risk factor for chronic obstructive pulmonary
disease (COPD). Serving military personnel have previously been shown to be more
likely to smoke, and to smoke more heavily, than civilians, but there is no clear
consensus as to whether in later life, as veterans, they experience a higher
prevalence and mortality from COPD than do non-veterans. We examined the risk of
COPD in Scottish veterans and assessed the impact of changes in military smoking.
METHODS: Retrospective 30-year cohort study of 56 205 veterans born 1945-1985,
and 172 741 people with no record of military service, matched for age, sex and
area of residence, using Cox proportional hazard models to examine the
association between veteran status, birth cohort, length of service and risk of
COPD resulting in hospitalisation or death. RESULTS: There were 1966 (3.52%)
cases of COPD meeting the definition in veterans, compared with 5434 (3.19%) in
non-veterans. The difference was statistically significant (p=0.001) in the
unadjusted model although it became non-significant after adjusting for
deprivation. The highest risk was seen in the oldest (1945-1949) birth cohort and
in veterans with the shortest service (Early Service Leavers). The risk was
significantly reduced in veterans born from 1960, and in those with over 12
years' service. CONCLUSIONS: Our findings are consistent with falling rates of
military smoking since the 1960s, and with the reduction in smoking with longer
service. The oldest veterans, and those with the shortest service, are least
likely to have benefited from this, as reflected in their higher risk for COPD.
PMID- 28500148
TI - One Health pioneer Lord Soulsby dies.
PMID- 28500149
TI - Record numbers vote in RCVS elections.
PMID- 28500150
TI - Team cow - BCVA marks 50th anniversary with charity push.
PMID- 28500154
TI - Suspected adverse events, 2015.
AB - The following article has been produced by the pharmacovigilance unit at the
Veterinary Medicines Directorate (VMD) to provide a summary of some of the
results from its surveillance work carried out in 2015Decrease in number of
reports for food-producing speciesIncrease in number of pet animal reportsReports
of dogs affected by medicines intended for large animals.
PMID- 28500155
TI - Improving safety through changes to the practice culture.
PMID- 28500157
TI - Possible effect of diet on stress and neuroendocrine parameters in dogs with
behavioural disorders.
PMID- 28500158
TI - Possible effect of diet on stress and neuroendocrine parameters in dogs with
behavioural disorders.
PMID- 28500159
TI - Business after Brexit.
PMID- 28500160
TI - Summer meeting of the Veterinary Invertebrate Society.
PMID- 28500161
TI - Helping feed bees and pollinators.
PMID- 28500169
TI - Making an impact through research.
AB - Julie Fitzpatrick grew up in rural Ayrshire, surrounded by dogs, cats, ponies and
other animals, with aspirations of working in mixed practice. She now heads the
Moredun Group in Edinburgh.
PMID- 28500170
TI - JAK2 inhibitors for myeloproliferative neoplasms: what is next?
AB - Since its approval in 2011, the Janus kinase 1/2 (JAK1/2) inhibitor ruxolitinib
has evolved to become the centerpiece of therapy for myelofibrosis (MF), and its
use in patients with hydroxyurea resistant or intolerant polycythemia vera (PV)
is steadily increasing. Several other JAK2 inhibitors have entered clinical
testing, but none have been approved and many have been discontinued.
Importantly, the activity of these agents is not restricted to patients with JAK2
V617F or exon 12 mutations. Although JAK2 inhibitors provide substantial clinical
benefit, their disease-modifying activity is limited, and rational combinations
with other targeted agents are needed, particularly in MF, in which survival is
short. Many such combinations are being explored, as are other novel agents, some
of which could successfully be combined with JAK2 inhibitors in the future. In
addition, new JAK2 inhibitors with the potential for less myelosuppression
continue to be investigated. Given the proven safety and efficacy of ruxolitinib,
it is likely that ruxolitinib-based combinations will be a major way forward in
drug development for MF. If approved, less myelosuppressive JAK2 inhibitors such
as pacritinib or NS-018 could prove to be very useful additions to the
therapeutic armamentarium in MF. In PV, inhibitors of histone deacetylases and
human double minute 2 have activity, but their role, if any, in the future
treatment algorithm is uncertain, given the availability of ruxolitinib and
renewed interest in interferons. Ruxolitinib is in late-phase clinical trials in
essential thrombocythemia, in which it could fill an important void for patients
with troublesome symptoms.
PMID- 28500172
TI - Induced Pluripotent Stem Cell-Derived Cardiomyocytes Provide In Vivo Biological
Pacemaker Function.
AB - BACKGROUND: Although multiple approaches have been used to create biological
pacemakers in animal models, induced pluripotent stem cell-derived cardiomyocytes
(iPSC-CMs) have not been investigated for this purpose. We now report pacemaker
function of iPSC-CMs in a canine model. METHODS AND RESULTS: Embryoid bodies were
derived from human keratinocytes, their action potential characteristics
determined, and their gene expression profiles and markers of differentiation
identified. Atrioventricular blocked dogs were immunosuppressed, instrumented
with VVI pacemakers, and injected subepicardially into the anterobasal left
ventricle with 40 to 75 rhythmically contracting embryoid bodies (totaling 1.3
2*106 cells). ECG and 24-hour Holter monitoring were performed biweekly. After 4
to 13 weeks, epinephrine (1 MUg kg-1 min-1) was infused, and the heart removed
for histological or electrophysiological study. iPSC-CMs largely lost the markers
of pluripotency, became positive for cardiac-specific markers. and manifested If
dependent automaticity. Epicardial pacing of the injection site identified
matching beats arising from that site by week 1 after implantation. By week 4,
20% of beats were electronically paced, 60% to 80% of beats were matching, and
mean and maximal biological pacemaker rates were 45 and 75 beats per minute.
Maximum night and day rates of matching beats were 53+/-6.9 and 69+/-10.4 beats
per minute, respectively, at 4 weeks. Epinephrine increased rate of matching
beats from 35+/-4.3 to 65+/-4.0 beats per minute. Incubation of embryoid bodies
with the vital dye, Dil, revealed the persistence of injected cells at the site
of administration. CONCLUSIONS: iPSC-CMs can integrate into host myocardium and
create a biological pacemaker. Although this is a promising development, rate and
rhythm of the iPSC-CMs pacemakers remain to be optimized.
PMID- 28500173
TI - TGF-beta1 (Transforming Growth Factor-beta1) Plays a Pivotal Role in Cardiac
Myofibroblast Arrhythmogenicity.
AB - BACKGROUND: TGF-beta1 (transforming growth factor-beta1) importantly contributes
to cardiac fibrosis by controlling differentiation, migration, and collagen
secretion of cardiac myofibroblasts. It is still elusive, however, to which
extent TGF-beta1 alters the electrophysiological phenotype of myofibroblasts and
cardiomyocytes and whether it affects proarrhythmic myofibroblast-cardiomyocyte
crosstalk observed in vitro. METHODS AND RESULTS: Patch-clamp recordings of
cultured neonatal rat ventricular myofibroblasts revealed that TGF-beta1, applied
for 24 to 48 hours at clinically relevant concentrations (<=2.5 ng/mL), causes
substantial membrane depolarization concomitant with a several-fold increase of
transmembrane currents. Transcriptome analysis revealed TGF-beta1-dependent
changes in 29 of 63 ion channel/pump/connexin transcripts, indicating a
pleiotropic effect on the electrical phenotype of myofibroblasts. Whereas not
affecting cardiomyocyte membrane potentials and cardiomyocyte-cardiomyocyte gap
junctional coupling, TGF-beta1 depolarized cardiomyocytes coupled to
myofibroblasts by ~20 mV and increased gap junctional coupling between
myofibroblasts and cardiomyocytes >5-fold as reflected by elevated connexin 43
and consortin transcripts. TGF-beta1-dependent cardiomyocyte depolarization
resulted from electrotonic crosstalk with myofibroblasts as demonstrated by
immediate normalization of cardiomyocyte electrophysiology after targeted
disruption of coupled myofibroblasts and by cessation of ectopic activity of
cardiomyocytes coupled to myofibroblasts during pharmacological gap junctional
uncoupling. In cardiac fibrosis models exhibiting slow conduction and ectopic
activity, block of TGF-beta1 signaling completely abolished both arrhythmogenic
conditions. CONCLUSIONS: TGF-beta1 profoundly alters the electrophysiological
phenotype of cardiac myofibroblasts. Apart from possibly contributing to the
control of cell function in general, the changes proved to be pivotal for
proarrhythmic myofibroblast-cardiomyocyte crosstalk in vitro, which suggests that
TGF-beta1 may play a potentially important role in arrhythmogenesis of the
fibrotic heart.
PMID- 28500171
TI - Platelet microparticles infiltrating solid tumors transfer miRNAs that suppress
tumor growth.
AB - Platelet-derived microparticles (PMPs) are associated with enhancement of
metastasis and poor cancer outcomes. Circulating PMPs transfer platelet microRNAs
(miRNAs) to vascular cells. Solid tumor vasculature is highly permeable, allowing
the possibility of PMP-tumor cell interaction. Here, we show that PMPs infiltrate
solid tumors in humans and mice and transfer platelet-derived RNA, including
miRNAs, to tumor cells in vivo and in vitro, resulting in tumor cell apoptosis.
MiR-24 was a major species in this transfer. PMP transfusion inhibited growth of
both lung and colon carcinoma ectopic tumors, whereas blockade of miR-24 in tumor
cells accelerated tumor growth in vivo, and prevented tumor growth inhibition by
PMPs. Conversely, Par4-deleted mice, which had reduced circulating microparticles
(MPs), supported accelerated tumor growth which was halted by PMP transfusion.
PMP targeting was associated with tumor cell apoptosis in vivo. We identified
direct RNA targets of platelet-derived miR-24 in tumor cells, which included
mitochondrial mt-Nd2, and Snora75, a noncoding small nucleolar RNA. These RNAs
were suppressed in PMP-treated tumor cells, resulting in mitochondrial
dysfunction and growth inhibition, in an miR-24-dependent manner. Thus, platelet
derived miRNAs transfer in vivo to tumor cells in solid tumors via infiltrating
MPs, regulate tumor cell gene expression, and modulate tumor progression. These
findings provide novel insight into mechanisms of horizontal RNA transfer and add
multiple layers to the regulatory roles of miRNAs and PMPs in tumor progression.
Plasma MP-mediated transfer of regulatory RNAs and modulation of gene expression
may be a common feature with important outcomes in contexts of enhanced vascular
permeability.
PMID- 28500174
TI - Effect of Digoxin Use Among Medicaid Enrollees With Atrial Fibrillation.
AB - BACKGROUND: Recently published analysis of contemporary atrial fibrillation (AF)
cohorts showed an association between digoxin and increased mortality and
hospitalizations; however, other studies have demonstrated conflicting results.
Many AF cohort studies did not or were unable to examine racial differences. Our
goal was to examine risk factors for hospitalizations and mortality with digoxin
use in a diverse real-world AF patient population and evaluate racial
differences. METHODS AND RESULTS: We performed a retrospective cohort analysis of
claims data for Medicaid beneficiaries, aged 18 to 64 years, with incident
diagnosis of AF in 2008 with follow-up until December 31, 2009. We created Kaplan
Meier curves and constructed multivariable Cox proportional hazard models for
mortality and hospitalization. We identified 11 297 patients with an incident
diagnosis of AF in 2008, of those, 1401 (12.4%) were on digoxin. Kaplan-Meier
analysis demonstrated an increased risk of hospitalization with digoxin use
overall and within race and heart failure groups. In adjusted models, digoxin was
associated with an increased risk of hospitalization (adjusted hazard ratio,
1.54; 95% confidence interval, 1.39-1.70) and mortality (adjusted hazard ratio,
1.50; 95% confidence interval, 1.05-2.13). Overall, blacks had a higher risk of
hospitalization but similar mortality when compared with whites regardless of
digoxin use. We found no significant interaction between race and digoxin use for
mortality (P=0.4437) and hospitalization (P=0.7122). CONCLUSIONS: Our study
demonstrates an overall increased risk of hospitalizations and mortality with
digoxin use but no racial/ethnic differences in outcomes were observed. Further
studies including minority populations are needed to critically evaluate these
associations.
PMID- 28500175
TI - Spatial Resolution Requirements for Accurate Identification of Drivers of Atrial
Fibrillation.
AB - BACKGROUND: Recent studies have demonstrated conflicting mechanisms underlying
atrial fibrillation (AF), with the spatial resolution of data often cited as a
potential reason for the disagreement. The purpose of this study was to
investigate whether the variation in spatial resolution of mapping may lead to
misinterpretation of the underlying mechanism in persistent AF. METHODS AND
RESULTS: Simulations of rotors and focal sources were performed to estimate the
minimum number of recording points required to correctly identify the underlying
AF mechanism. The effects of different data types (action potentials and unipolar
or bipolar electrograms) and rotor stability on resolution requirements were
investigated. We also determined the ability of clinically used endocardial
catheters to identify AF mechanisms using clinically recorded and simulated data.
The spatial resolution required for correct identification of rotors and focal
sources is a linear function of spatial wavelength (the distance between
wavefronts) of the arrhythmia. Rotor localization errors are larger for
electrogram data than for action potential data. Stationary rotors are more
reliably identified compared with meandering trajectories, for any given spatial
resolution. All clinical high-resolution multipolar catheters are of sufficient
resolution to accurately detect and track rotors when placed over the rotor core
although the low-resolution basket catheter is prone to false detections and may
incorrectly identify rotors that are not present. CONCLUSIONS: The spatial
resolution of AF data can significantly affect the interpretation of the
underlying AF mechanism. Therefore, the interpretation of human AF data must be
taken in the context of the spatial resolution of the recordings.
PMID- 28500176
TI - Mitral-Aortic Flow Reversal in Cardiac Resynchronization Therapy: Coupling With
Ejection and Impact of Variations in Atrioventricular Delay.
AB - BACKGROUND: Flow entering the left ventricle is reversed toward the outflow tract
through rotating reversal flow around the mitral valve. This was thought to
facilitate early ejection, but had not been proved to date. We hypothesized that
perfect coupling between reversal and ejection flow would occur at optimal
atrioventricular delay (AVD), contributing to its hemodynamic superiority, and
evaluated its applicability for AVD optimization. METHODS AND RESULTS: Forty
consecutive patients with cardiac resynchronization therapy underwent
intracardiac flow analysis and AVD optimization. Reversal and ejection flow
curves were studied. The presence and duration of reversal-ejection discontinuity
were assessed for all programmed AVD. Reproducibility of each optimization method
was evaluated through interobserver variability. Discontinuity between reversal
and ejection flow was observed in all patients with longer than optimal AVD,
increasing linearly with excess duration in AVD (linear R2=0.976, P<0.001).
Longer discontinuities implied progressive decreases in pre-ejection flow
velocity in the left ventricular outflow tract, with consequent loss of flow
momentum. The equation optimal AVD=programmed AVD-[1.2(discontinuity duration)]+4
accurately predicted optimal AVD. Short AVD systematically compromised reversal
flow because of premature ejection. Agreement over optimal AVD was superior when
assessed by flow reversal method (intraclass correlation coefficient =0.931;
P<0.001) over both iterative and aortic velocity-time integral methods.
CONCLUSIONS: Perfect coupling between mitral-aortic flow reversal and ejection
flow in the left ventricle occurs at optimal AVD. As a result, full blood
momentum in the outflow tract is used to facilitate early ejection. This can be
measured and provides a new method for AVD optimization.
PMID- 28500177
TI - Efficacy of an Anatomical Approach in Radiofrequency Catheter Ablation of
Idiopathic Ventricular Arrhythmias Originating From the Left Ventricular Outflow
Tract.
AB - BACKGROUND: When anatomic obstacles preclude radiofrequency catheter ablation of
idiopathic ventricular arrhythmias (VAs) originating from the left ventricular
outflow tract (LVOT), an alternative approach from the anatomically opposite side
(endocardial versus epicardial or above versus below the aortic valve) may be
considered (anatomic ablation). The purpose of this study was to investigate the
efficacy of an anatomic ablation in idiopathic LVOT VAs. METHODS AND RESULTS: We
studied 229 consecutive patients with idiopathic LVOT VAs. Radiofrequency
ablation from the first suitable site was successful in 190 patients, and in the
remaining 39 patients, it was unsuccessful or had to be abandoned because of
anatomic obstacles. In 22 of these 39 patients, an anatomic ablation was
successful, and the VA origins were located in the intramural LVOT in 17
patients, basal left ventricular summit in 4, and LVOT septum near the His bundle
in 1. The anatomic ablation was highly successful for idiopathic VAs originating
from the intramural LVOT (>75%) and lateral LVOT, whereas it was unlikely to be
successful for idiopathic VAs originating from the basal left ventricular summit
(25%) and sepal LVOT. CONCLUSIONS: When a standard catheter ablation targeting
the best electrophysiological measure of idiopathic LVOT VAs was unsuccessful or
had to be abandoned because of anatomic obstacles, an anatomic ablation was
moderately successful. These idiopathic LVOT VAs with a successful anatomic
ablation commonly arose from the intramural LVOT among the left coronary cusp,
aortomitral continuity, and epicardium, occasionally the basal left ventricular
summit, and rarely the LVOT septum near the His bundle.
PMID- 28500180
TI - Induced Pluripotent Stem Cell-Based Treatment of Acquired Heart Block: The Battle
for Tomorrow Has Begun!
PMID- 28500179
TI - Is TGF-beta1 (Transforming Growth Factor-beta1) an Enabler of Myofibroblast
Cardiomyocyte Cross Talk?
PMID- 28500178
TI - Electrical Substrate Elimination in 135 Consecutive Patients With Brugada
Syndrome.
AB - BACKGROUND: There is emerging evidence that localization and elimination of
abnormal electric activity in the epicardial right ventricular outflow tract may
be beneficial in patients with Brugada syndrome. METHODS AND RESULTS: A total of
135 symptomatic Brugada syndrome patients having implantable cardiac
defibrillator were enrolled: 63 (group 1) having documented ventricular
tachycardia (VT)/ventricular fibrillation (VF) and Brugada syndrome-related
symptoms, and 72 (group 2) having inducible VT/VF without ECG documentation at
the time of symptoms. About 27 patients of group 1 experienced multiple
implantable cardiac defibrillator shocks for recurrent VT/VF episodes. Three
dimensional maps before and after ajmaline determined the arrhythmogenic
electrophysiological substrate (AES) as characterized by prolonged fragmented
ventricular potentials. Primary end point was identification and elimination of
AES leading to ECG pattern normalization and VT/VF noninducibility. Extensive
areas of AES were found in the right ventricle epicardium, which were wider in
group 1 (P=0.007). AES increased after ajmaline in both groups (P<0.001) and was
larger in men (P=0.008). The increase of type-1 ST-segment elevation correlated
with AES expansion (r=0.682, P<0.001). Radiofrequency ablation eliminated AES
leading to ECG normalization and VT/VF noninducibility in all patients. During a
median follow-up of 10 months, the ECG remained normal even after ajmaline in all
except 2 patients who underwent a repeated effective procedure for recurrent VF.
CONCLUSIONS: In Brugada syndrome, AES is commonly located in the right ventricle
epicardium and ajmaline exposes its extent and distribution, which is correlated
with the degree of coved ST-elevation. AES elimination by radiofrequency ablation
results in ECG normalization and VT/VF noninducibility. Substrate-based ablation
is effective in potentially eliminating the arrhythmic consequences of this
genetic disease. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov.
Unique identifier: NCT02641431.
PMID- 28500181
TI - Nucleolar caspase-2: Protecting us from DNA damage.
AB - Caspase-2 triggers apoptosis, but how it is activated by different stimuli is
unclear. In this issue, Ando et al. (2017. J. Cell Biol.
https://doi.org/10.1083/jcb.201608095) delineate two pathways of caspase-2
activation and show that, in response to DNA damage, caspase-2 forms a complex
with the PIDDosome and NPM1 within the nucleolus.
PMID- 28500182
TI - UPR transducer BBF2H7 allows export of type II collagen in a cargo- and
developmental stage-specific manner.
AB - The unfolded protein response (UPR) handles unfolded/misfolded proteins
accumulated in the endoplasmic reticulum (ER). However, it is unclear how
vertebrates correctly use the total of ten UPR transducers. We have found that ER
stress occurs physiologically during early embryonic development in medaka fish
and that the smooth alignment of notochord cells requires ATF6 as a UPR
transducer, which induces ER chaperones for folding of type VIII (short-chain)
collagen. After secretion of hedgehog for tissue patterning, notochord cells
differentiate into sheath cells, which synthesize type II collagen. In this
study, we show that this vacuolization step requires both ATF6 and BBF2H7 as UPR
transducers and that BBF2H7 regulates a complete set of genes (Sec23/24/13/31,
Tango1, Sedlin, and KLHL12) essential for the enlargement of COPII vesicles to
accommodate long-chain collagen for export, leading to the formation of the
perinotochordal basement membrane. Thus, the most appropriate UPR transducer is
activated to cope with the differing physiological ER stresses of different
content types depending on developmental stage.
PMID- 28500184
TI - Does not compute.
PMID- 28500186
TI - Medication access via hospital admission.
PMID- 28500188
TI - End-of-life care.
PMID- 28500183
TI - The chromokinesin Klp3a and microtubules facilitate acentric chromosome
segregation.
AB - Although poleward segregation of acentric chromosomes is well documented, the
underlying mechanisms remain poorly understood. Here, we demonstrate that
microtubules play a key role in poleward movement of acentric chromosome
fragments generated in Drosophila melanogaster neuroblasts. Acentrics segregate
with either telomeres leading or lagging in equal frequency and are
preferentially associated with peripheral bundled microtubules. In addition,
laser ablation studies demonstrate that segregating acentrics are mechanically
associated with microtubules. Finally, we show that successful acentric
segregation requires the chromokinesin Klp3a. Reduced Klp3a function results in
disorganized interpolar microtubules and shortened spindles. Normally, acentric
poleward segregation occurs at the periphery of the spindle in association with
interpolar microtubules. In klp3a mutants, acentrics fail to localize and
segregate along the peripheral interpolar microtubules and are abnormally
positioned in the spindle interior. These studies demonstrate an unsuspected role
for interpolar microtubules in driving acentric segregation.
PMID- 28500189
TI - Choice is led by values.
PMID- 28500190
TI - Response.
PMID- 28500191
TI - Family physicians' role in hidradenitis suppurativa management.
PMID- 28500193
TI - Viral myositis in children.
AB - Question I recently evaluated a child in my clinic after an emergency department
visit where she presented having woken up that morning refusing to walk and was
crawling around the house. The parents reported she was getting over a cold, and
I recall similar cases of myositis during the H1N1 influenza epidemic a few years
ago. What are the key features of myositis that I should recognize? Which
investigations are needed to confirm the diagnosis and how should affected
patients be managed? Answer Benign acute childhood myositis is a mild and self
limited sudden onset of lower extremity pain during or following recovery from a
viral illness. Presentation can include tiptoe gait or refusal to walk, secondary
to symmetric bilateral lower extremity pain that resolves quickly, usually within
3 days. In general, no investigation is needed except in severe cases for which
screening bloodwork and a urine myoglobin test can confirm the diagnosis and rule
out complications. Myoglobinuria and highly elevated creatine phosphokinase
levels are rare but should be a consideration for admission to hospital.
Prognosis is excellent and management might include rest and analgesia.
PMID- 28500192
TI - Deprescribing proton pump inhibitors: Evidence-based clinical practice guideline.
AB - OBJECTIVE: To develop an evidence-based guideline to help clinicians make
decisions about when and how to safely taper or stop proton pump inhibitors
(PPIs); to focus on the highest level of evidence available and seek input from
primary care professionals in the guideline development, review, and endorsement
processes. METHODS: Five health professionals (1 family physician, 3 pharmacists,
and 1 gastroenterologist) and 5 nonvoting members comprised the overall team;
members disclosed conflicts of interest. The guideline process included the GRADE
(Grading of Recommendations Assessment, Development and Evaluation) approach,
with a detailed evidence review in in-person, telephone, and online meetings.
Uniquely, the guideline development process included a systematic review of PPI
deprescribing trials and examination of reviews of the harm of continued PPI use.
Narrative syntheses of patient preferences and resource-implication literature
informed recommendations. The team refined guideline content and recommendation
wording through consensus and synthesized clinical considerations to address
common front-line clinician questions. The draft guideline was distributed to
clinicians and then to health care professional associations for review and
revisions made at each stage. A decision-support algorithm was developed in
conjunction with the guideline. RECOMMENDATIONS: This guideline recommends
deprescribing PPIs (reducing dose, stopping, or using "on-demand" dosing) in
adults who have completed a minimum of 4 weeks of PPI treatment for heartburn or
mild to moderate gastroesophageal reflux disease or esophagitis, and whose
symptoms are resolved. The recommendations do not apply to those who have or have
had Barrett esophagus, severe esophagitis grade C or D, or documented history of
bleeding gastrointestinal ulcers. CONCLUSION: This guideline provides practical
recommendations for making decisions about when and how to reduce the dose of or
stop PPIs. Recommendations are meant to assist with, not dictate, decision making
in conjunction with patients.
PMID- 28500195
TI - Glucagonlike peptide 1 analogs in diabetes care.
PMID- 28500194
TI - Million dollar ride: Crime committed during involuntary scopolamine intoxication.
PMID- 28500196
TI - Choosing Wisely Canada.
PMID- 28500197
TI - Establishing and growing the scope of practice of physician assistants.
PMID- 28500198
TI - Triple antithrombotic therapy for atrial fibrillation and coronary stents.
PMID- 28500200
TI - Hope.
PMID- 28500199
TI - Data quality in electronic medical records in Manitoba: Do problem lists reflect
chronic disease as defined by prescriptions?
AB - OBJECTIVE: To determine if the problem list (health conditions) in primary care
electronic medical records (EMRs) accurately reflects the conditions for which
chronic medications are prescribed in the EMR. DESIGN: A retrospective analysis
of EMR data. SETTING: Eighteen primary care clinics across rural and urban
Manitoba using the Accuro EMR. PARTICIPANTS: Data from the EMRs of active
patients seen in an 18-month period (December 18, 2011, to June 18, 2013, or
December 3, 2012, to June 3, 2014) were used. MAIN OUTCOME MEASURES: The
likelihood of documentation in the EMR problem list of those specific chronic
diseases for which drug prescriptions were documented in the EMR. Regression
modeling was performed to determine the effect of clinic patient load and
remuneration type on the completeness of EMR problem lists. RESULTS: Overall
problem-list completeness was low but was highest for diabetes and lowest for
insomnia. Fee-for-service clinics generally had lower problem-list completeness
than salaried clinics did for all prescription medications examined. Panel size
did not affect problem-list completeness rates. CONCLUSION: The low EMR problem
list completeness suggests that this field is not reliable for use in quality
improvement initiatives or research until higher reliability has been
demonstrated. Further research is recommended to explore the reasons for the poor
quality and to support improvement efforts.
PMID- 28500201
TI - Thinking like a rebel: Listening to patients, partnering with disease, finding
the inspiration in suffering.
PMID- 28500202
TI - Osteoporosis management in residential care: How internal and family medicine
resident physicians translate evidence into practice.
PMID- 28500203
TI - Indigenous health: time for action.
PMID- 28500206
TI - Comprehensiveness revisited: Family Medicine Responsibility Profile.
PMID- 28500210
TI - First-line medications for alcohol use disorders among public drug plan
beneficiaries in Ontario.
AB - OBJECTIVE: To examine use of first-line alcohol use disorder (AUD) medications
(naltrexone and acamprosate) among public drug plan beneficiaries in the year
following an AUD diagnosis. DESIGN: Retrospective population-based cohort study.
SETTING: Ontario. PARTICIPANTS: Individuals eligible for public drug plan
benefits who had an AUD diagnosis at a hospital visit between April 1, 2011, and
March 31, 2012. MAIN OUTCOME MEASURES: Number of AUD medications dispensed to
public drug plan beneficiaries who had a recent hospital visit with an AUD
diagnosis, and number of prescriptions dispensed per person. RESULTS: A total of
10 394 Ontarians between 18 and 65 years of age were identified who had a
hospital visit with an AUD diagnosis and were eligible for public drug plan
benefits. The rate of AUD medications dispensed in the subsequent year was 3.56
per 1000 population (95% CI 2.51 to 4.91; n = 37). This rate did not differ
significantly by sex (P = .83). CONCLUSION: Very few public drug plan
beneficiaries are dispensed first-line AUD medications in the year following an
AUD diagnosis.
PMID- 28500211
TI - Computer use in primary care practices in Canada.
AB - OBJECTIVE: To examine the use of computers in primary care practices. DESIGN: The
international Quality and Cost of Primary Care study was conducted in Canada in
2013 and 2014 using a descriptive cross-sectional survey method to collect data
from practices across Canada. Participating practices filled out several surveys,
one of them being the Family Physician Survey, from which this study collected
its data. SETTING: All 10 Canadian provinces. PARTICIPANTS: A total of 788 family
physicians. MAIN OUTCOME MEASURES: A computer use scale measured the extent to
which family physicians integrated computers into their practices, with higher
scores indicating a greater integration of computer use in practice. Analyses
included t tests and 2 tests comparing new and traditional models of primary care
on measures of computer use and electronic health record (EHR) use, as well as
descriptive statistics. RESULTS: Nearly all (97.5%) physicians reported using a
computer in their practices, with moderately high computer use scale scores (mean
[SD] score of 5.97 [2.96] out of 9), and many (65.7%) reported using EHRs.
Physicians with practices operating under new models of primary care reported
incorporating computers into their practices to a greater extent (mean [SD] score
of 6.55 [2.64]) than physicians operating under traditional models did (mean [SD]
score of 5.33 [3.15]; t726.60 = 5.84; P < .001; Cohen d = 0.42, 95% CI 0.808 to
1.627) and were more likely to report using EHRs (73.8% vs 56.7%; [Formula: see
text]; P < .001; odds ratio = 2.15). Overall, there was a statistically
significant variability in computer use across provinces. CONCLUSION: Most family
physicians in Canada have incorporated computers into their practices for
administrative and scholarly activities; however, EHRs have not been adopted
consistently across the country. Physicians with practices operating under the
new, more collaborative models of primary care use computers more comprehensively
and are more likely to use EHRs than those in practices operating under
traditional models of primary care.
PMID- 28500214
TI - Efficacy of the Telemedical Lifestyle intervention Program TeLiPro in Advanced
Stages of Type 2 Diabetes: A Randomized Controlled Trial.
AB - OBJECTIVE: Lifestyle interventions are the foundation of treatment in newly
diagnosed type 2 diabetes. However, their therapeutic potential in advanced
disease stages is unknown. We evaluated the efficacy of the Telemedical Lifestyle
intervention Program (TeLiPro) in improving metabolic control in advanced-stage
type 2 diabetes. RESEARCH DESIGN AND METHODS: In this single-blind, active
comparator, intervention study, patients with type 2 diabetes (with glycated
hemoglobin [HbA1c] >=7.5% [58.5 mmol/mol]), and BMI >=27 kg/m2 and on >=2
antidiabetes medications) were recruited in Germany and randomized 1:1 using an
electronically generated random list and sealed envelopes into two parallel
groups. The data analyst was blinded after assignment. The control group (n =
100) got weighing scales and step counters and remained in routine care. The
TeLiPro group (n = 102) additionally received telemedical coaching including
medical-mental motivation, a formula diet, and self-monitored blood glucose for
12 weeks. The primary end point was the estimated treatment difference in HbA1c
reduction after 12 weeks. All available values per patient (n = 202) were
analyzed. Analyses were also performed at 26 and 52 weeks of follow-up. RESULTS:
HbA1c reduction was significantly higher in the TeLiPro group (mean +/- SD -1.1
+/- 1.2% vs. -0.2 +/- 0.8%; P < 0.0001). The estimated treatment difference in
the fully adjusted model was 0.8% (95% CI 1.1; 0.5) (P < 0.0001). Treatment
superiority of TeLiPro was maintained during follow-up (week 26: 0.6% [95% CI
1.0; 0.3], P = 0.0001; week 52: 0.6% [0.9; 0.2], P < 0.001). The same applies for
secondary outcomes: weight (TeLiPro -6.2 +/- 4.6 kg vs. control -1.0 +/- 3.4 kg),
BMI (-2.1 +/- 1.5 kg/m2 vs. -0.3 +/- 1.1 kg/m2), systolic blood pressure (-5.7 +/
15.3 mmHg vs. -1.6 +/- 13.8 mmHg), 10-year cardiovascular disease risk,
antidiabetes medication, and quality of life and eating behavior (P < 0.01 for
all). The effects were maintained long-term. No adverse events were reported.
CONCLUSIONS: In advanced-stage type 2 diabetes, TeLiPro can improve glycemic
control and may offer new options to avoid pharmacological intensification.
PMID- 28500215
TI - A National Effort to Prevent Type 2 Diabetes: Participant-Level Evaluation of
CDC's National Diabetes Prevention Program.
AB - OBJECTIVE: To assess participant-level results from the first 4 years of
implementation of the National Diabetes Prevention Program (National DPP), a
national effort to prevent type 2 diabetes in those at risk through structured
lifestyle change programs. RESEARCH DESIGN AND METHODS: Descriptive analysis was
performed on data from 14,747 adults enrolled in year-long type 2 diabetes
prevention programs during the period February 2012 through January 2016. Data on
attendance, weight, and physical activity minutes were summarized and predictors
of weight loss were examined using a mixed linear model. All analyses were
performed using SAS 9.3. RESULTS: Participants attended a median of 14 sessions
over an average of 172 days in the program (median 134 days). Overall, 35.5%
achieved the 5% weight loss goal (average weight loss 4.2%, median 3.1%).
Participants reported a weekly average of 152 min of physical activity (median
128 min), with 41.8% meeting the physical activity goal of 150 min per week. For
every additional session attended and every 30 min of activity reported,
participants lost 0.3% of body weight (P < 0.0001). CONCLUSIONS: During the first
4 years, the National DPP has achieved widespread implementation of the lifestyle
change program to prevent type 2 diabetes, with promising early results. Greater
duration and intensity of session attendance resulted in a higher percent of body
weight loss overall and for subgroups. Focusing on retention may reduce
disparities and improve overall program results. Further program expansion and
investigation is needed to continue lowering the burden of type 2 diabetes
nationally.
PMID- 28500218
TI - NHS in danger of falling behind with out of date scanners, warn experts.
PMID- 28500216
TI - Metformin, Lifestyle Intervention, and Cognition in the Diabetes Prevention
Program Outcomes Study.
AB - OBJECTIVE: We examined the association of the Diabetes Prevention Program (DPP)
intervention arms (lifestyle intervention, metformin, and placebo) with cognition
in the Diabetes Prevention Program Outcomes Study (DPPOS). We also examined
metformin use, incident type 2 diabetes, and glycemia as exposures. RESEARCH
DESIGN AND METHODS: The DPP lasted 2.8 years, followed by a 13-month bridge to
DPPOS. Cognition was assessed in DPPOS years 8 and 10 (12 and 14 years after
randomization) with the Spanish English Verbal Learning Test (SEVLT), letter
fluency and animal fluency tests, Digit Symbol Substitution Test (DSST), and a
composite cognitive score. RESULTS: A total of 2,280 participants (749 lifestyle,
776 metformin, and 755 placebo) aged 63.1 +/- 10.7 years underwent cognitive
assessments; 67.7% women, 54.6% non-Hispanic white, 20.7% non-Hispanic black,
14.6% Hispanic, 5.5% American Indian, and 4.6% Asian; 26.6% were homozygous or
heterozygous for APOE-epsilon4. At the time of cognitive assessment, type 2
diabetes was higher in the placebo group (57.9%; P < 0.001) compared with
lifestyle (47.0%) and metformin (50.4%). Metformin exposure was higher in the
metformin group (8.72 years; P < 0.001) compared with placebo (1.43 years) and
lifestyle (0.96 years). There were no differences in cognition across
intervention arms. Type 2 diabetes was not related to cognition, but higher
glycated hemoglobin at year 8 was related to worse cognition after confounder
adjustment. Cumulative metformin exposure was not related to cognition.
CONCLUSIONS: Exposure to intensive lifestyle intervention or metformin was not
related to cognition among DPPOS participants. Higher glycemia was related to
worse cognitive performance. Metformin seemed cognitively safe among DPPOS
participants.
PMID- 28500217
TI - Glucose Peaks and the Risk of Dementia and 20-Year Cognitive Decline.
AB - OBJECTIVE: Hemoglobin A1c (HbA1c), a measure of average blood glucose level, is
associated with the risk of dementia and cognitive impairment. However, the role
of glycemic variability or glucose excursions in this association is unclear. We
examined the association of glucose peaks in midlife, as determined by the
measurement of 1,5-anhydroglucitol (1,5-AG) level, with the risk of dementia and
20-year cognitive decline. RESEARCH DESIGN AND METHODS: Nearly 13,000
participants from the Atherosclerosis Risk in Communities (ARIC) study were
examined. Dementia was ascertained from surveillance, neuropsychological testing,
telephone calls with participants or their proxies, or death certificate dementia
codes. Cognitive function was assessed using three neuropsychological tests at
three visits over 20 years and was summarized as z scores. We used Cox and linear
mixed-effects models. 1,5-AG level was dichotomized at 10 MUg/mL and examined
within clinical categories of HbA1c. RESULTS: Over a median time of 21 years,
dementia developed in 1,105 participants. Among persons with diabetes, each 5
MUg/mL decrease in 1,5-AG increased the estimated risk of dementia by 16% (hazard
ratio 1.16, P = 0.032). For cognitive decline among participants with diabetes
and HbA1c <7% (53 mmol/mol), those with glucose peaks had a 0.19 greater z score
decline over 20 years (P = 0.162) compared with those without peaks. Among
participants with diabetes and HbA1c >=7% (53 mmol/mol), those with glucose peaks
had a 0.38 greater z score decline compared with persons without glucose peaks (P
< 0.001). We found no significant associations in persons without diabetes.
CONCLUSIONS: Among participants with diabetes, glucose peaks are a risk factor
for cognitive decline and dementia. Targeting glucose peaks, in addition to
average glycemia, may be an important avenue for prevention.
PMID- 28500219
TI - Mechanisms of Enhanced Phrenic Long-Term Facilitation in SOD1G93A Rats.
AB - Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease,
causing muscle paralysis and death from respiratory failure. Effective means to
preserve/restore ventilation are necessary to increase the quality and duration
of life in ALS patients. At disease end-stage in a rat ALS model (SOD1G93A ),
acute intermittent hypoxia (AIH) restores phrenic nerve activity to normal levels
via enhanced phrenic long-term facilitation (pLTF). Mechanisms enhancing pLTF in
end-stage SOD1G93A rats are not known. Moderate AIH-induced pLTF is normally
elicited via cellular mechanisms that require the following: Gq-protein-coupled 5
HT2 receptor activation, new BDNF synthesis, and MEK/ERK signaling (the Q
pathway). In contrast, severe AIH elicits pLTF via a distinct mechanism that
requires the following: Gs-protein-coupled adenosine 2A receptor activation, new
TrkB synthesis, and PI3K/Akt signaling (the S pathway). In end-stage male
SOD1G93A rats and wild-type littermates, we investigated relative Q versus S
pathway contributions to enhanced pLTF via intrathecal (C4) delivery of small
interfering RNAs targeting BDNF or TrkB mRNA, and MEK/ERK (U0126) or PI3
kinase/Akt (PI828) inhibitors. In anesthetized, paralyzed and ventilated rats,
moderate AIH-induced pLTF was abolished by siBDNF and UO126, but not siTrkB or
PI828, demonstrating that enhanced pLTF occurs via the Q pathway. Although
phrenic motor neuron numbers were decreased in end-stage SOD1G93A rats (~30%
survival; p < 0.001), BDNF and phosphorylated ERK expression were increased in
spared phrenic motor neurons (p < 0.05), consistent with increased Q-pathway
contributions to pLTF. Our results increase understanding of respiratory
plasticity and its potential to preserve/restore breathing capacity in
ALS.SIGNIFICANCE STATEMENT Since neuromuscular disorders, such as amyotrophic
lateral sclerosis (ALS), end life via respiratory failure, the ability to harness
respiratory motor plasticity to improve breathing capacity could increase the
quality and duration of life. In a rat ALS model (SOD1G93A ) we previously
demonstrated that spinal respiratory motor plasticity elicited by acute
intermittent hypoxia is enhanced at disease end-stage, suggesting greater
potential to preserve/restore breathing capacity. Here we demonstrate that
enhanced intermittent hypoxia-induced phrenic motor plasticity results from
amplification of normal cellular mechanisms versus addition/substitution of
alternative mechanisms. Greater understanding of mechanisms underlying phrenic
motor plasticity in ALS may guide development of new therapies to preserve and/or
restore breathing in ALS patients.
PMID- 28500221
TI - Ubiquitin C-Terminal Hydrolase L1 (UCH-L1) Promotes Hippocampus-Dependent Memory
via Its Deubiquitinating Effect on TrkB.
AB - Multiple studies have established that brain-derived neurotrophic factor (BDNF)
plays a critical role in the regulation of synaptic plasticity via its receptor,
TrkB. In addition to being phosphorylated, TrkB has also been demonstrated to be
ubiquitinated. However, the mechanisms of TrkB ubiquitination and its biological
functions remain poorly understood. In this study, we demonstrate that ubiquitin
C-terminal hydrolase L1 (UCH-L1) promotes contextual fear conditioning learning
and memory via the regulation of ubiquitination of TrkB. We provide evidence that
UCH-L1 can deubiquitinate TrkB directly. K460 in the juxtamembane domain of TrkB
is the primary ubiquitination site and is regulated by UCH-L1. By using a peptide
that competitively inhibits the association between UCH-L1 and TrkB, we show that
the blockade of UCH-L1-regulated TrkB deubiquitination leads to increased BDNF
induced TrkB internalization and consequently directs the internalized TrkB to
the degradation pathway, resulting in increased degradation of surface TrkB and
attenuation of TrkB activation and its downstream signaling pathways. Moreover,
injection of the peptide into the DG region of mice impairs hippocampus-dependent
memory. Together, our results suggest that the ubiquitination of TrkB is a
mechanism that controls its downstream signaling pathways via the regulation of
its endocytosis and postendocytic trafficking and that UCH-L1 mediates the
deubiquitination of TrkB and could be a potential target for the modulation of
hippocampus-dependent memory.SIGNIFICANCE STATEMENT Ubiquitin C-terminal
hydrolase L1 (UCH-L1) has been demonstrated to play important roles in the
regulation of synaptic plasticity and learning and memory. TrkB, the receptor for
brain-derived neurotrophic factor, has also been shown to be a potent regulator
of synaptic plasticity. In this study, we demonstrate that UCH-L1 functions as a
deubiquitinase for TrkB. The blockage of UCH-L1-regulated deubiquitination of
TrkB eventually results in the increased degradation of surface TrkB and
decreased activation of TrkB and its downstream signaling pathways. In vivo, UCH
L1-regulated TrkB deubiquitination is necessary for hippocampus-dependent memory.
Overall, our study provides novel insights into the mechanisms of UCH-L1-mediated
neurobiological functions and suggests that ubiquitination is an important
regulatory signal for TrkB functions.
PMID- 28500222
TI - Energy Requirements of Odor Transduction in the Chemosensory Cilia of Olfactory
Sensory Neurons Rely on Oxidative Phosphorylation and Glycolytic Processing of
Extracellular Glucose.
AB - The mechanisms that power the physiological events occurring in cilia, flagella,
and microvilli are of fundamental importance for the functions of these important
and ubicuous organelles. The olfactory epithelium is mostly populated by ciliated
olfactory sensory neurons (OSNs) and surrounding sustentacular cells (SCs) with
apical microvilli. The only OSN dendrite extends to the surface forming a knob
projecting several chemosensory cilia of ~50 * 0.2 MUm, devoid of inner membranes
embedded in a mucus layer. Upon odorant binding, odor receptors couple to G
protein activating adenylyl cyclase, producing cAMP. cAMP opens cyclic nucleotide
gated channels allowing a Ca2+ influx that opens Ca2+-activated Cl- channels,
generating the receptor potential. Many enzymes are activated in
chemotransduction to hydrolyze ATP. The knob contains approximately two
mitochondria; assuming that the cilia ATP is 1 mm and diffuses along it at ~10
MUm in 500 ms, ATP from the knob mitochondria may not fulfill the demands of
transduction over the full length of the cilium, which suggests an additional ATP
source. We measured millimolar glucose in rat mucus; we detected glucose
transporter GLUT3 in rat and toad (Caudiverbera caudiverbera) OSN cilia, SC
microvilli, and glycolytic enzymes in rat cilia. We also found that the cilia and
knob can incorporate and accumulate 2-deoxyglucose (glucose analog), but not when
blocking GLUT. Glucose removal and the inhibition of glycolysis or oxidative
phospholylation impaired the odor response. This evidence strongly suggests that
glycolysis in the cilia and knob oxidative phosphorylation together fuel
chemotransduction.SIGNIFICANCE STATEMENT How processes occurring in cilia and
flagella are powered is a matter of general interest. Substantial progress has
been made in unraveling the sensory transduction mechanisms, commonly occurring
in such structures; however, the energy sources powering them have been scarcely
explored. Accessibility to the specialized sensory organelles and their small
dimensions have been limiting factors. Olfactory sensory neurons chemosensory
cilia are elongated, mucus embedded, fully exposed structures particularly
amenable for a multidisciplinary study of this problem, as done here. We
demonstrate the occurrence and functionality of glucose uptake and glycolysis in
the cilia. We support that odor transduction relies on ATP generated by oxidative
phosphorylation in the dendrite and glycolytically in the cilia using glucose
internalized from the mucus.
PMID- 28500220
TI - Environmental Enrichment Rescues Binocular Matching of Orientation Preference in
the Mouse Visual Cortex.
AB - Neural circuits are shaped by experience during critical periods of development.
Sensory deprivation during these periods permanently compromises an organism's
ability to perceive the outside world. In the mouse visual system, normal visual
experience during a critical period in early life drives the matching of
individual cortical neurons' orientation preferences through the two eyes, likely
a key step in the development of binocular vision. Here, in mice of both sexes,
we show that the binocular matching process is completely blocked by monocular
deprivation spanning the entire critical period. We then show that 3 weeks of
environmental enrichment (EE), a paradigm of enhanced sensory, motor, and
cognitive stimulation, is sufficient to rescue binocular matching to the level
seen in unmanipulated mice. In contrast, 6 weeks of conventional housing only
resulted in a partial rescue. Finally, we use two-photon calcium imaging to track
the matching process chronically in individual cells during EE-induced rescue. We
find that for cells that are clearly dominated by one of the two eyes, the input
representing the weaker eye changes its orientation preference to align with that
of the dominant eye. These results thus reveal ocular dominance as a key driver
of the binocular matching process, and suggest a model whereby the dominant input
instructs the development of the weaker input. Such a mechanism may operate in
the development of other systems that need to integrate inputs from multiple
sources to generate normal neuronal functions.SIGNIFICANCE STATEMENT Critical
periods are developmental windows of opportunity that ensure the proper wiring of
neural circuits, as well as windows of vulnerability when abnormal experience
could cause lasting damage to the developing brain. In the visual system,
critical period plasticity drives the establishment of binocularly matched
orientation preferences in cortical neurons. Here, we show that binocular
matching is completely blocked by monocular deprivation during the critical
period. Moreover, environmental enrichment can fully rescue the disrupted
matching, whereas conventional housing of twice the duration results in a partial
rescue. We then use two-photon calcium imaging to track individual cells
chronically during the EE-induced recovery, and reveal important insights into
how appropriate function can be restored to the nervous system after the critical
period.
PMID- 28500223
TI - Thirty-Year Mortality After Coronary Artery Bypass Graft Surgery: A Danish
Nationwide Population-Based Cohort Study.
AB - BACKGROUND: Data are sparse on long-term mortality after coronary artery bypass
graft (CABG) surgery. We examined short-term and long-term mortality of patients
undergoing CABG surgery and a general population comparison cohort. METHODS AND
RESULTS: Linking data from Danish registries, we conducted a nationwide,
population-based cohort study on 51 307 CABG patients and 513 070 individuals
from the general population matched on age, sex, and calendar year (1980-2009).
The mortality risk was higher in patients having isolated CABG surgery than in
the general population, particularly during 0 to 30 days (3.2% versus 0.2%), 11
to 20 years (51.1% versus 35.6%), and 21 to 30 years (62.4% versus 44.8%), but
not substantially higher during 31 to 364 days (2.9% versus 2.4%) or 1 to 10
years (30.7% versus 25.8%). The 30-day adjusted mortality rate ratio for isolated
CABG surgery was 13.51 (95% confidence interval [CI], 12.59-14.49). Between 31 to
364 days and 1 to 10 years, the isolated CABG surgery cohort had a slightly
higher mortality rate than the general population comparison cohort, adjusted
mortality rate ratios of 1.15 (95% CI, 1.09-1.21) and 1.09 (95% CI, 1.08-1.11),
respectively. Between 11 to 20 years and 21 to 30 years, the adjusted mortality
rate ratios were 1.62 (95% CI, 1.58-1.66) and 1.76 (95% CI, 1.62-1.91). Within 30
days, CABG patients had a 25-fold, a 26-fold, and a 18-fold higher risk of dying
from myocardial infarction, heart failure, or stroke, respectively, than members
of the general population comparison cohort. We found substantial heterogeneity
in absolute mortality rates according to baseline risk groups. CONCLUSIONS: The
isolated CABG cohort had a higher mortality rate than the general population
comparison cohort, especially within 30 days of and 10 years after surgery.
PMID- 28500225
TI - Zika virus infection-associated acute transient polyneuritis.
PMID- 28500224
TI - Evaluating the safety of beta-interferons in MS: A series of nested case-control
studies.
AB - OBJECTIVE: To examine the association between interferon-beta (IFN-beta) and
potential adverse events using population-based health administrative data in
British Columbia, Canada. METHODS: Patients with relapsing-remitting multiple
sclerosis (RRMS) who were registered at a British Columbia Multiple Sclerosis
Clinic (1995-2004) were eligible for inclusion and were followed up until death,
absence from British Columbia, exposure to a non-IFN-beta disease-modifying drug,
or December 31, 2008. Incidence rates were estimated for each potential adverse
event (selected a priori and defined with ICD-9/10 diagnosis codes from physician
and hospital claims). A nested case-control study was conducted to assess the
odds of previous IFN-beta exposure for each potential adverse event with at least
30 cases. Cases were matched by age (+/-5 years), sex, and year of cohort entry,
with up to 20 randomly selected (by incidence density sampling) controls. Odds
ratios (ORs) with 95% confidence intervals (95% CIs) were estimated with
conditional logistic regression adjusted for age at cohort entry. RESULTS: Of the
2,485 eligible patients, 77.9% were women, and 1,031 were treated with IFN-beta
during follow-up. From the incidence analyses, 27 of the 47 potential adverse
events had at least 30 cases. Patients with incident stroke (ORadj 1.83, 95% CI
1.16-2.89), migraine (ORadj 1.55, 95% CI 1.18-2.04), depression (ORadj 1.33, 95%
CI 1.13-1.56), and hematologic abnormalities (ORadj 1.32, 95% CI 1.01-1.72) were
more likely to have previous exposure to IFN-beta than controls. CONCLUSIONS:
Among patients with RRMS, IFN-beta was associated with a 1.8- and 1.6-fold
increase in the risk of stroke and migraine and 1.3-fold increases in depression
and hematologic abnormalities.
PMID- 28500226
TI - MR perfusion lesions after TIA or minor stroke are associated with new infarction
at 7 days.
AB - OBJECTIVE: To investigate the relationship between acute perfusion-weighted
imaging (PWI) lesions occurring within the first hours after a TIA or a minor
brain infarction (BI) and the incidence of new BI detected on a systematic MRI at
1 week. METHODS: Consecutive patients who experienced a TIA or BI with a
neurologic deficit that lasted <24 hours, did not receive any revascularization
therapy (thrombolysis/thrombectomy), and underwent DWI/PWI at baseline and fluid
attenuated inversion recovery (FLAIR)/DWI 1 week after symptom onset were
enrolled. Investigators blinded to clinical information independently assessed
the presence of acute ischemic lesions on baseline DWI/PWI and follow-up DWI and
FLAIR. Baseline and follow-up MRIs were then compared to determine the occurrence
and location of new infarctions. RESULTS: Sixty-four patients met the inclusion
criteria. Median (IQR) ABCD2 score was 4 (3-5). Median delay from onset to
baseline and follow-up MRI was 5 (2-10) hours and 6 (5-7) days, respectively. MRI
revealed an acute ischemic lesion on DWI and/or PWI in 38 patients. Nine patients
(14%) had a new infarction on follow-up MRI. Each had a PWI and 4 had a DWI
lesion on baseline MRI. All new BIs except one were asymptomatic and in the same
location as the acute PWI lesion. CONCLUSIONS: Our results showed that 30% of the
acute focal PWI lesions detected after a TIA are associated with a new BI at 1
week. Those new BIs may result from the progression of the initial ischemic
injury.
PMID- 28500228
TI - A liana from the lower Miocene of Panama and the fossil record of Connaraceae.
AB - PREMISE OF THE STUDY: Permineralized wood is common in the Miocene beds exposed
during the expansion of the Panama Canal. We describe a stem with the distinctive
anatomy of a liana and evaluate the evolutionary, biogeographic, and ecological
significance of this discovery. METHODS: The object of the study was obtained
from a collection of fossil woods and fruits from a locality in the lower Miocene
Cucaracha Formation, where the formation is exposed by the Culebra Cut of the
Panama Canal. Thin sections were prepared using the cellulose acetate peel
technique and examined using transmitted light microscopy. We described the
anatomy and compared it with that of extant and fossil species. We also reviewed
and evaluated published reports of fossils attributed to Connaraceae. KEY
RESULTS: The anatomy of this fossil wood matches the genus Rourea (Connaraceae).
The stem is only 1 cm in diameter, but vessels >200 MUm in diameter also occur,
indicating the perennial climbing habit. We evaluated 12 other pre-Quaternary
occurrences attributed to Connaraceae. Four are accepted, three are rejected, and
we consider five unknown or uncertain. CONCLUSIONS: The discovery of this Rourea
stem confirms the presence of Connaraceae in the Neotropics by the early Miocene,
provides the oldest evidence of the climbing habit in the family, and contributes
to our understanding of the flora of Panama 19 mya. Although the fossil record of
Connaraceae is sparse, reliable occurrences span three continents and indicate
that the family originated as early as the Late Cretaceous-Paleocene and was
widespread by the early Miocene.
PMID- 28500227
TI - Neurofilament markers for ALS correlate with extent of upper and lower motor
neuron disease.
AB - OBJECTIVE: To determine the diagnostic performance and prognostic value of
phosphorylated neurofilament heavy chain (pNfH) and neurofilament light chain
(NfL) in CSF as possible biomarkers for amyotrophic lateral sclerosis (ALS) at
the diagnostic phase. METHODS: We measured CSF pNfH and NfL concentrations in 220
patients with ALS, 316 neurologic disease controls (DC), and 50 genuine disease
mimics (DM) to determine and assess the accuracy of the diagnostic cutoff value
for pNfH and NfL and to correlate with other clinical parameters. RESULTS: pNfH
was most specific for motor neuron disease (specificity 88.2% [confidence
interval (CI) 83.0%-92.3%]). pNfH had the best performance to differentially
diagnose patients with ALS from DM with a sensitivity of 90.7% (CI 84.9%-94.8%),
a specificity of 88.0% (CI 75.7%-95.5%) and a likelihood ratio of 7.6 (CI 3.6
16.0) at a cutoff of 768 pg/mL. CSF pNfH and NfL levels were significantly lower
in slow disease progressors, however, with a poor prognostic performance with
respect to the disease progression rate. CSF pNfH and NfL levels increased
significantly as function of the number of regions with both upper and lower
motor involvement. CONCLUSIONS: In particular, CSF pNfH concentrations show an
added value as diagnostic biomarkers for ALS, whereas the prognostic value of
pNfH and NfL warrants further investigation. Both pNfH and NfL correlated with
the extent of motor neuron degeneration. CLASSIFICATION OF EVIDENCE: This study
provides Class II evidence that elevated concentrations of CSF pNfH and NfL can
accurately identify patients with ALS.
PMID- 28500229
TI - Isolation by distance and isolation by environment contribute to population
differentiation in Protea repens (Proteaceae L.), a widespread South African
species.
AB - PREMISE OF THE STUDY: The Cape Floristic Region (CFR) of South Africa is renowned
for its botanical diversity, but the evolutionary origins of this diversity
remain controversial. Both neutral and adaptive processes have been implicated in
driving diversification, but population-level studies of plants in the CFR are
rare. Here, we investigate the limits to gene flow and potential environmental
drivers of selection in Protea repens L. (Proteaceae L.), a widespread CFR
species. METHODS: We sampled 19 populations across the range of P. repens and
used genotyping by sequencing to identify 2066 polymorphic loci in 663
individuals. We used a Bayesian FST outlier analysis to identify single
nucleotide polymorphisms (SNPs) marking genomic regions that may be under
selection; we used those SNPs to identify potential drivers of selection and
excluded them from analyses of gene flow and genetic structure. RESULTS: A
pattern of isolation by distance suggested limited gene flow between nearby
populations. The populations of P. repens fell naturally into two or three
groupings, which corresponded to an east-west split. Differences in rainfall
seasonality contributed to diversification in highly divergent loci, as do
barriers to gene flow that have been identified in other species. CONCLUSIONS:
The strong pattern of isolation by distance is in contrast to the findings in the
only other widespread species in the CFR that has been similarly studied, while
the effects of rainfall seasonality are consistent with well-known patterns.
Assessing the generality of these results will require investigations of other
CFR species.
PMID- 28500230
TI - Conjunctival lymphangiectasia associated with classic Fabry disease.
AB - BACKGROUND: Fabry disease (FD) is a treatable multisystem disease caused by a
defect in the alpha-galactosidase gene. Ocular signs of FD, including corneal
verticillata, are among the earliest diagnostic findings. Conjunctival
lymphangiectasia (CL) has not previously been associated with FD. METHODS: We
examined the eyes of a cohort of 13 adult patients, eight men and five women,
with documented classic FD, all treated with enzyme replacement therapy (ERT) at
the University of Alabama at Birmingham between February 2014 and April 2015. The
average age was 48 years with a range of 35-55 years for men and 21-71 years for
women. The mean duration of ERT was 8.4 years (men 8.9 years, women 7.6 years)
with a range of 4-14 years. Classical Fabry mutations included Q283X, R227X,
W236X and W277X. A high resolution Haag-Streit BQ-900 slit lamp with EyeCap
imaging system was used to record conjunctival images. RESULTS: CL was observed
in 11 of the 13 patients (85%) despite long-term ERT. Clinical presentations
included single cysts, beaded dilatations and areas of conjunctival oedema.
Lesions were located within 6 mm of the corneal limbus. Ten of the 13 subjects
(77%) had Fabry-related cataracts and all 13 demonstrated bilateral corneal
verticillata. Twelve of the 13 patients had evidence of dry eye, 9 of whom were
symptomatic, and 10 had peripheral lymphoedema. CONCLUSION: CL represents a
common but under-recognised ocular manifestation of FD, which persists despite
ERT, and is often accompanied by peripheral lymphoedema and dry eye syndrome.
PMID- 28500231
TI - Discovery of a Novel Small-Molecule Inhibitor that Targets PP2A-beta-Catenin
Signaling and Restricts Tumor Growth and Metastasis.
AB - Molecular hybridization of different pharmacophores to tackle both tumor growth
and metastasis by a single molecular entity can be very effective and unique if
the hybrid product shows drug-like properties. Here, we report synthesis and
discovery of a novel small-molecule inhibitor of PP2A-beta-catenin signaling that
limits both in vivo tumor growth and metastasis. Our molecular hybridization
approach resulted in cancer cell selectivity and improved drug-like properties of
the molecule. Inhibiting PP2A and beta-catenin interaction by selectively
engaging PR55alpha-binding site, our most potent small-molecule inhibitor
diminished the expression of active beta-catenin and its target proteins c-Myc
and Cyclin D1. Furthermore, it promotes robust E-cadherin upregulation on the
cell surface and increases beta-catenin-E-Cadherin association, which may prevent
dissemination of metastatic cells. Altogether, we report synthesis and
mechanistic insight of a novel drug-like molecule to differentially target beta
catenin functionality via interacting with a particular subunit of PP2A. Mol
Cancer Ther; 16(9); 1791-805. (c)2017 AACR.
PMID- 28500232
TI - NKG2D Ligand-Targeted Bispecific T-Cell Engagers Lead to Robust Antitumor
Activity against Diverse Human Tumors.
AB - Two new bispecific T-cell engaging (BiTE) molecules with specificity for NKG2D
ligands were developed and functionally characterized. One, huNKG2D-OKT3, was
derived from the extracellular portion of the human NKG2D receptor fused to a
CD3epsilon binding single-chain variable fragment (scFv), known as OKT3. NKG2D
has multiple ligands, including MICA, which are expressed by a variety of
malignant cells. A second molecule, B2-OKT3, was created in the tandem scFv BiTE
format that targets MICA on tumor cells and CD3epsilon on human T cells. Both
BiTEs specifically activated T cells to kill human tumor cell lines. Cytotoxicity
by B2-OKT3, but not huNKG2D-OKT3, is blocked by soluble rMICA. The huNKG2D-OKT3
induced greater T-cell cytokine production in comparison with B2-OKT3. No T-cell
pretreatment was required for IFNgamma production upon coculture of B2-OKT3 or
huNKG2D-OKT3 with T cells and target cells. The effector memory T-cell
compartment was the primary source of IFNgamma, and culture of T cells and these
BiTEs with plate-bound rMICA showed ligand density-dependent production of
IFNgamma from both CD4+ and CD8+ T cells. There was 2-fold more IFNgamma produced
per CD8+ T cell and 5-fold greater percentage of CD8+ T cells producing IFNgamma
compared with CD4+ T cells. In addition, both BiTEs elicited significant
antitumor responses against human metastatic melanoma tumor samples using
autologous or healthy donor T cells. These data demonstrate the robust antitumor
activity of these NKG2D ligand-binding bispecific proteins and support their
further development for clinical use. Mol Cancer Ther; 16(7); 1335-46. (c)2017
AACR.
PMID- 28500233
TI - Nanoformulation of Olaparib Amplifies PARP Inhibition and Sensitizes PTEN/TP53
Deficient Prostate Cancer to Radiation.
AB - The use of PARP inhibitors in combination with radiotherapy is a promising
strategy to locally enhance DNA damage in tumors. Here we show that radiation
resistant cells and tumors derived from a Pten/Trp53-deficient mouse model of
advanced prostate cancer are rendered radiation sensitive following treatment
with NanoOlaparib, a lipid-based injectable nanoformulation of olaparib. This
enhancement in radiosensitivity is accompanied by radiation dose-dependent
changes in gamma-H2AX expression and is specific to NanoOlaparib alone. In
animals, twice-weekly intravenous administration of NanoOlaparib results in
significant tumor growth inhibition, whereas previous studies of oral olaparib as
monotherapy have shown no therapeutic efficacy. When NanoOlaparib is administered
prior to radiation, a single dose of radiation is sufficient to triple the median
mouse survival time compared to radiation only controls. Half of mice treated
with NanoOlaparib + radiation achieved a complete response over the 13-week study
duration. Using ferumoxytol as a surrogate nanoparticle, MRI studies revealed
that NanoOlaparib enhances the intratumoral accumulation of systemically
administered nanoparticles. NanoOlaparib-treated tumors showed up to 19-fold
higher nanoparticle accumulation compared to untreated and radiation-only
controls, suggesting that the in vivo efficacy of NanoOlaparib may be potentiated
by its ability to enhance its own accumulation. Together, these data suggest that
NanoOlaparib may be a promising new strategy for enhancing the radiosensitivity
of radiation-resistant tumors lacking BRCA mutations, such as those with PTEN and
TP53 deletions. Mol Cancer Ther; 16(7); 1279-89. (c)2017 AACR.
PMID- 28500234
TI - Niclosamide and Bicalutamide Combination Treatment Overcomes Enzalutamide- and
Bicalutamide-Resistant Prostate Cancer.
AB - Activation of the androgen receptor (AR) and its splice variants is linked to
advanced prostate cancer and drives resistance to antiandrogens. The roles of AR
and AR variants in the development of resistance to androgen deprivation therapy
(ADT) and bicalutamide treatment, however, are still incompletely understood. To
determine whether AR variants play a role in bicalutamide resistance, we
developed bicalutamide-resistant LNCaP cells (LNCaP-BicR) and found that these
resistant cells express significantly increased levels of AR variants,
particularly AR-V7, both at the mRNA and protein levels. Exogenous expression of
AR-V7 in bicalutamide-sensitive LNCaP cells confers resistance to bicalutamide
treatment. Knockdown of AR-V7 in bicalutamide- and enzalutamide-resistant
CWR22Rv1, enzalutamide-resistant C4-2B (C4-2B MDVR), and LNCaP-BicR cells
reversed bicalutamide resistance. Niclosamide, a potent inhibitor of AR variants,
significantly enhanced bicalutamide treatment. Niclosamide and bicalutamide
combination treatment not only suppressed AR and AR variants expression and
inhibited their recruitment to the PSA promoter, but also significantly induced
apoptosis in bicalutamide- and enzalutamide-resistant CWR22Rv1 and C4-2B MDVR
cells. In addition, combination of niclosamide with bicalutamide inhibited the
growth of enzalutamide-resistant tumors. In summary, our results demonstrate that
AR variants, particularly AR-V7, drive bicalutamide resistance and that targeting
AR-V7 with niclosamide can resensitize bicalutamide-resistant cells to
bicalutamide treatment. Furthermore, combination of niclosamide with bicalutamide
inhibits enzalutamide resistant tumor growth, suggesting that the combination of
niclosamide and bicalutamide could be a potential cost-effective strategy to
treat advanced prostate cancer in patients, including those who fail to respond
to enzalutamide therapy. Mol Cancer Ther; 16(8); 1521-30. (c)2017 AACR.
PMID- 28500235
TI - beta-Catenin Inhibitor BC2059 Is Efficacious as Monotherapy or in Combination
with Proteasome Inhibitor Bortezomib in Multiple Myeloma.
AB - Currently available treatment options are unlikely to be curative for the
majority of multiple myeloma patients, emphasizing a continuing role for the
introduction of investigational agents that can overcome drug resistance. The
canonical Wnt/beta-catenin signaling pathway, essential for self-renewal, growth,
and survival, has been found to be dysregulated in multiple myeloma, particularly
in advanced stages of disease. This provides the rationale for evaluating the
novel beta-catenin inhibitor BC2059 as monotherapy and in combination with
proteasome inhibitors in vitro and in vivo Here, we show nuclear localization of
beta-catenin in human myeloma cell lines (HMCL), consistent with activation of
the canonical Wnt pathway. BC2059 attenuates beta-catenin levels, in both the
cytoplasm and the nucleus, reducing the transcriptional activity of the TCF4/LEF
complex and the expression of its target gene axin 2. Treatment of HMCL with
BC2059 inhibits proliferation and induces apoptosis in a dose-dependent manner.
This is also observed in HMCL-stromal cell cocultures, mitigating the protective
effect afforded by the stroma. Similarly, BC2059 induces apoptosis in primary
multiple myeloma samples in vitro, causing minimal apoptosis on healthy
peripheral blood mononuclear cells. Furthermore, it synergizes with the
proteasome inhibitor bortezomib both in HMCL and primary multiple myeloma
samples. Finally, in xenograft models of human myelomatosis, BC2059 delays tumor
growth and prolongs survival with minor on-target side effects. Collectively,
these results demonstrate the efficacy of targeting the Wnt/beta-catenin pathway
with BC2059 both in vitro and in vivo, at clinically achievable doses. These
findings support further clinical evaluation of BC2059 for the treatment of
multiple myeloma. Mol Cancer Ther; 16(9); 1765-78. (c)2017 AACR.
PMID- 28500236
TI - Identification of the Serine Biosynthesis Pathway as a Critical Component of BRAF
Inhibitor Resistance of Melanoma, Pancreatic, and Non-Small Cell Lung Cancer
Cells.
AB - Metastatic melanoma cells commonly acquire resistance to BRAF V600E inhibitors
(BRAFi). In this study, we identified serine biosynthesis as a critical mechanism
of resistance. Proteomic assays revealed differential protein expression of
serine biosynthetic enzymes PHGDH, PSPH, and PSAT1 following vemurafenib (BRAFi)
treatment in sensitive versus acquired resistant melanoma cells. Ablation of
PHGDH via siRNA sensitized acquired resistant cells to vemurafenib. Inhibiting
the folate cycle, directly downstream of serine synthesis, with methotrexate also
displayed similar sensitization. Using the DNA-damaging drug gemcitabine, we show
that gemcitabine pretreatment sensitized resistant melanoma cells to BRAFis
vemurafenib and dabrafenib. We extended our findings to BRAF WT tumor cell lines
that are intrinsically resistant to vemurafenib and dabrafenib. Pretreatment of
pancreatic cancer and non-small cell lung cancer cell lines with sublethal doses
of 50 and 5 nmol/L of gemcitabine, respectively, enhanced killing by both
vemurafenib and dabrafenib. The novel aspects of this study are the direct
identification of serine biosynthesis as a critical mechanism of BRAF V600E
inhibitor resistance and the first successful example of using gemcitabine +
BRAFis in combination to kill previously drug-resistant cancer cells, creating
the translational potential of pretreatment with gemcitabine prior to BRAFi
treatment of tumor cells to reverse resistance within the mutational profile and
the WT. Mol Cancer Ther; 16(8); 1596-609. (c)2017 AACR.
PMID- 28500238
TI - SDHA mutated paragangliomas may be at high risk of metastasis.
PMID- 28500239
TI - Vacuolar and plasma membrane proton pumps collaborate to achieve cytosolic pH
homeostasis in yeast.
PMID- 28500237
TI - Resistance to RET-Inhibition in RET-Rearranged NSCLC Is Mediated By Reactivation
of RAS/MAPK Signaling.
AB - Oncogenic rearrangements in RET are present in 1%-2% of lung adenocarcinoma
patients. Ponatinib is a multi-kinase inhibitor with low-nanomolar potency
against the RET kinase domain. Here, we demonstrate that ponatinib exhibits
potent antiproliferative activity in RET fusion-positive LC-2/ad lung
adenocarcinoma cells and inhibits phosphorylation of the RET fusion protein and
signaling through ERK1/2 and AKT. Using distinct dose escalation strategies, two
ponatinib-resistant LC-2/ad cell lines, PR1 and PR2, were derived. PR1 and PR2
cell lines retained expression, but not phosphorylation of the RET fusion and
lacked evidence of a resistance mutation in the RET kinase domain. Both resistant
lines retained activation of the MAPK pathway. Next-generation RNA sequencing
revealed an oncogenic NRAS p.Q61K mutation in the PR1 cell. PR1 cell
proliferation was preferentially sensitive to siRNA knockdown of NRAS compared
with knockdown of RET, more sensitive to MEK inhibition than the parental line,
and NRAS dependence was maintained in the absence of chronic RET inhibition.
Expression of NRAS p.Q61K in RET fusion expressing TPC1 cells conferred
resistance to ponatinib. PR2 cells exhibited increased expression of EGFR and
AXL. EGFR inhibition decreased cell proliferation and phosphorylation of ERK1/2
and AKT in PR2 cells, but not LC-2/ad cells. Although AXL inhibition enhanced PR2
sensitivity to afatinib, it was unable to decrease cell proliferation by itself.
Thus, EGFR and AXL cooperatively rescued signaling from RET inhibition in the PR2
cells. Collectively, these findings demonstrate that resistance to ponatinib in
RET-rearranged lung adenocarcinoma is mediated by bypass signaling mechanisms
that result in restored RAS/MAPK activation. Mol Cancer Ther; 16(8); 1623-33.
(c)2017 AACR.
PMID- 28500240
TI - A carboxyl ester lipase (CEL) mutant causes chronic pancreatitis by forming
intracellular aggregates that activate apoptosis.
PMID- 28500241
TI - A plague of actin disassembly.
AB - Pathogenic Yersinia species employ several strategies to evade the host immune
system, including interfering with cytoskeletal remodeling as a way to block
macrophage phagocytosis. The kinase YopO binds directly to monomeric actin and
phosphorylates the actin-remodeling protein gelsolin, but the functional
importance of this gelsolin modification has not been clear. A combined
biochemical, computational, and biophysical study now reveals that YopO-mediated
phosphorylation activates host gelsolin, leading to severed actin filaments and
disturbed actin dynamics.
PMID- 28500242
TI - Rotational atherectomy: re-emergence of an old technique.
PMID- 28500243
TI - Aerobic fitness, muscular strength and obesity in relation to risk of heart
failure.
AB - OBJECTIVE: Low physical fitness and obesity have been associated with higher risk
of developing heart failure (HF), but their interactive effects are unknown.
Elucidation of interactions among these common modifiable factors may help
facilitate more effective primary prevention. METHODS: We conducted a national
cohort study to examine the interactive effects of aerobic fitness, muscular
strength and body mass index (BMI) among 1 330 610 military conscripts in Sweden
during 1969-1997 (97%-98% of all 18-year-old men) on risk of HF identified from
inpatient and outpatient diagnoses through 2012 (maximum age 62 years). RESULTS:
There were 11 711 men diagnosed with HF in 37.8 million person-years of follow
up. Low aerobic fitness, low muscular strength and obesity were independently
associated with higher risk of HF, after adjusting for each other, socioeconomic
factors, other chronic diseases and family history of HF. The combination of low
aerobic fitness and low muscular strength (lowest vs highest tertiles) was
associated with a 1.7-fold risk of HF (95% CI 1.6 to 1.9; p<0.001; incidence
rates per 100 000 person-years, 43.2 vs 10.8). These factors had positive
additive and multiplicative interactions (p<0.001) and were associated with
increased risk of HF even among men with normal BMI. CONCLUSIONS: Low aerobic
fitness, low muscular strength and obesity at the age of 18 years were
independently associated with higher risk of HF in adulthood, with interactive
effects between aerobic fitness and muscular strength. These findings suggest
that early-life interventions may help reduce the long-term risk of HF and should
include both aerobic fitness and muscular strength, even among persons with
normal BMI.
PMID- 28500244
TI - Tamoxifen reduces hepatic VLDL production and GH secretion in women: a possible
mechanism for steatosis development.
AB - CONTEXT: Growth hormone (GH) stimulates hepatic synthesis of very-low-density
lipoproteins (VLDL), whereas hepatic steatosis develops as a result of GH
deficiency. Steatosis is also a complication of tamoxifen treatment, the cause of
which is not known. As tamoxifen inhibits the secretion and action of GH, we
hypothesize that it induces steatosis by inhibiting hepatic VLDL export. AIM: To
investigate whether tamoxifen reduces hepatic VLDL secretion. DESIGN: Eight
healthy, normolipidemic women (age: 64.4 +/- 2.1 years) were studied in random
sequence at baseline, after 2 weeks of tamoxifen (20 mg/day) and after 2 weeks of
estradiol valerate (EV; 2 mg/day) treatments, separated by a 4-week washout
period. The kinetics of apolipoprotein B (apoB), the structural protein of VLDL
particles, were measured using a stable isotope 2H3-leucine turnover technique.
VLDL-apoB fractional catabolic rate (FCR) was determined using a multicompartment
model. VLDL-apoB secretion was estimated as the product of FCR and VLDL-apoB
concentration. GH response to arginine stimulation, circulating levels of IGF-1,
FFA, and TG, along with TG content in VLDL were measured. RESULTS: Tamoxifen
significantly (P < 0.05) reduced VLDL-apoB concentration and secretion by 27.3 +/
7.8% and 29.8 +/- 10.2%, respectively. In contrast, EV did not significantly
change VLDL-apoB concentration or secretion. Tamoxifen but not EV significantly
reduced (P < 0.05) GH response to arginine stimulation. Both treatments
significantly lowered (P < 0.05) circulating IGF-1. CONCLUSION: Inhibition of
VLDL secretion may contribute to the development of fatty liver during tamoxifen
therapy. As GH stimulates VLDL secretion, the development of steatosis may arise
secondarily from GH insufficiency induced by tamoxifen.
PMID- 28500245
TI - Pseudoacromegaly: an unusual presenting manifestation of long-standing
undiagnosed primary hypothyroidism.
PMID- 28500246
TI - Closing the theory to practice gap for newly qualified doctors: evaluation of a
peer-delivered practical skills training course for newly qualified doctors in
preparation for clinical practice.
AB - PURPOSE: The Good Intern Programme (GIP) in Sri Lanka has been implemented to
bridge the 'theory to practice gap' of doctors preparing for their internship.
This paper evaluates the impact of a 2-day peer-delivered Acute Care Skills
Training (ACST) course as part of the GIP. STUDY DESIGN: The ACST course was
developed by an interprofessional faculty, including newly graduated doctors
awaiting internship (pre-intern), focusing on the recognition and management of
common medical and surgical emergencies. Course delivery was entirely by pre
intern doctors to their peers. Knowledge was evaluated by a pre- and post-course
multiple choice test. Participants' confidence (post-course) and 12 acute care
skills (pre- and post-course) were assessed using Likert scale-based questions. A
subset of participants provided feedback on the peer learning experience.
RESULTS: Seventeen courses were delivered by a faculty consisting of eight peer
trainers over 4 months, training 320 participants. The mean (SD) multiple choice
questionnaire score was 71.03 (13.19) pre-course compared with 77.98 (7.7) post
course (p<0.05). Increased overall confidence in managing ward emergencies was
reported by 97.2% (n=283) of respondents. Participants rated their post-course
skills to be significantly higher (p<0.05) than pre-course in all 12 assessed
skills. Extended feedback on the peer learning experience was overwhelmingly
positive and 96.5% would recommend the course to a colleague. CONCLUSIONS: A peer
delivered ACST course was extremely well received and can improve newly qualified
medical graduates' knowledge, skills and confidence in managing medical and
surgical emergencies. This peer-based model may have utility beyond pre-interns
and beyond Sri Lanka.
PMID- 28500248
TI - The association of the lipidomic profile with features of polycystic ovary
syndrome.
AB - Polycystic ovary syndrome (PCOS) affects up to 18% of reproductive-aged women
with reproductive and metabolic complications. While lipidomics can identify
associations between lipid species and metabolic diseases, no research has
examined the association of lipid species with the pathophysiological features of
PCOS. The aim of this study was to examine the lipidomic profile in women with
and without PCOS. This study was a cross-sectional study in 156 age-matched pre
menopausal women (18-45 years, BMI >20 kg/m2; n = 92 with PCOS, n = 64 without
PCOS). Outcomes included the association between the plasma lipidomic profile
(325 lipid species (24 classes) using liquid chromatography mass spectrometry)
and PCOS, adiposity, homeostasis assessment of insulin resistance (HOMA), sex
hormone-binding globulin (SHBG) and free androgen index (FAI). There were no
associations of the lipidomic profile with PCOS or testosterone. HOMA was
positively associated with 2 classes (dihydroceramide and triacylglycerol), SHBG
was inversely associated with 2 classes (diacylglycerol and triacylglycerol), FAI
was positively associated with 8 classes (ceramide, phosphatidylcholine,
lysophosphatidylcholine, phosphatidylethanolamine, lysophosphatidylethanolamine,
phosphatidylinositol, diacylglycerol and triacylglycerol) and waist circumference
was associated with 8 classes (4 positively (dihydroceramide,
phosphatidylglycerol, diacylglycerol and triacylglycerol) and 4 inversely
(trihexosylceramide, GM3 ganglioside, alkenylphosphatidylcholine and
alkylphosphatidylethanolamine)). The lipidomic profile was primarily related to
central adiposity and FAI in women with or without PCOS. This supports prior
findings that adiposity is a key driver of dyslipidaemia in PCOS and highlights
the need for weight management through lifestyle interventions.
PMID- 28500249
TI - Maternal high-fat diet induces metabolic stress response disorders in offspring
hypothalamus.
AB - Maternal obesity has been shown to increase the risk of obesity and related
disorders in the offspring, which has been partially attributed to changes of
appetite regulators in the offspring hypothalamus. On the other hand, endoplasmic
reticulum (ER) stress and autophagy have been implicated in hypothalamic
neuropeptide dysregulation, thus may also play important roles in such
transgenerational effect. In this study, we show that offspring born to high-fat
diet-fed dams showed significantly increased body weight and glucose intolerance,
adiposity and plasma triglyceride level at weaning. Hypothalamic mRNA level of
the orexigenic neuropeptide Y (NPY) was increased, while the levels of the
anorexigenic pro-opiomelanocortin (POMC), NPY1 receptor (NPY1R) and melanocortin
4 receptor (MC4R) were significantly downregulated. In association, the
expression of unfolded protein response (UPR) markers including glucose-regulated
protein (GRP)94 and endoplasmic reticulum DNA J domain-containing protein (Erdj)4
was reduced. By contrast, protein levels of autophagy-related genes Atg5 and
Atg7, as well as mitophagy marker Parkin, were slightly increased. The
administration of 4-phenyl butyrate (PBA), a chemical chaperone of protein
folding and UPR activator, in the offspring from postnatal day 4 significantly
reduced their body weight, fat deposition, which were in association with
increased activating transcription factor (ATF)4, immunoglobulin-binding protein
(BiP) and Erdj4 mRNA as well as reduced Parkin, PTEN-induced putative kinase
(PINK)1 and dynamin-related protein (Drp)1 protein expression levels. These
results suggest that hypothalamic ER stress and mitophagy are among the
regulatory factors of offspring metabolic changes due to maternal obesity.
PMID- 28500250
TI - Characterization of NMB, GRP and their receptors (BRS3, NMBR and GRPR) in
chickens.
AB - The two structurally and functionally related peptides, gastrin-releasing peptide
(GRP) and neuromedin B (NMB) play critical roles in many
physiological/pathological processes in mammals. However, the information
regarding the expression and functionality of avian NMB, GRP and their receptors
is limited. Here, we characterized cNMB, cGRP and their receptors (cNMBR, cGRPR
and cBRS3) in chickens. Our results showed that: (1) cNMBR and cGRPR expressed in
CHO cells could be potently activated by cNMB and cGRP, respectively, as
monitored by cell-based luciferase reporter assays, indicating that cNMBR and
cGRPR are cNMB- and cGRP-specific receptors; strikingly, BRS3 of chickens
(/spotted gars), which is orthologous to mouse bombesin receptor subtype-3
(BRS3), could be potently activated by GRP and NMB, demonstrating that both
peptides are the endogenous ligands for chicken (/spotted gar) BRS3; (2)
quantitative real-time PCR (qPCR) revealed that cGRPR is widely expressed in
chicken tissues with abundant expression in the ovary, pancreas, proventriculus,
spinal cord and brain, whereas cNMB, cNMBR and cBRS3 are mainly expressed in the
brain and testes; (3) interestingly, qPCR, Western blot and immunostaining
revealed that cGRP is predominantly expressed in the anterior pituitary and
mainly localized to LH-cells, suggesting that cGRP is likely a novel pituitary
hormone in chickens. In summary, our data help to uncover the roles of GRP, NMB
and their receptors in birds, and provide the first persuasive evidence from an
evolutionary prospective that in vertebrates, GRP and NMB are the endogenous
ligands for BRS3, an orphan receptor that has puzzled endocrinologists for more
than two decades.
PMID- 28500252
TI - Transcriptome profiling reveals novel BMI- and sex-specific gene expression
signatures for human cardiac hypertrophy.
AB - How obesity or sex may affect the gene expression profiles of human cardiac
hypertrophy is unknown. We hypothesized that body-mass index (BMI) and sex can
affect gene expression profiles of cardiac hypertrophy. Human heart tissues were
grouped according to sex (male, female), BMI (lean<25 kg/m2, obese>30 kg/m2), or
left ventricular hypertrophy (LVH) and non-LVH nonfailed controls (NF). We
identified 24 differentially expressed (DE) genes comparing female with male
samples. In obese subgroup, there were 236 DE genes comparing LVH with NF; in
lean subgroup, there were seven DE genes comparing LVH with NF. In female
subgroup, we identified 1,320 significant genes comparing LVH with NF; in male
subgroup, there were 1,383 significant genes comparing LVH with NF. There were
seven significant genes comparing obese LVH with lean NF; comparing male obese
LVH with male lean NF samples we found 106 significant genes; comparing female
obese LVH with male lean NF, we found no significant genes. Using absolute value
of log2 fold-change > 2 or extremely small P value (10-20) as a criterion, we
identified nine significant genes (HBA1, HBB, HIST1H2AC, GSTT1, MYL7, NPPA, NPPB,
PDK4, PLA2G2A) in LVH, also found in published data set for ischemic and dilated
cardiomyopathy in heart failure. We identified a potential gene expression
signature that distinguishes between patients with high BMI or between men and
women with cardiac hypertrophy. Expression of established biomarkers atrial
natriuretic peptide A (NPPA) and B (NPPB) were already significantly increased in
hypertrophy compared with controls.
PMID- 28500251
TI - Expression of distinct maternal and somatic 5.8S, 18S, and 28S rRNA types during
zebrafish development.
AB - There is mounting evidence that the ribosome is not a static translation
machinery, but a cell-specific, adaptive system. Ribosomal variations have mostly
been studied at the protein level, even though the essential transcriptional
functions are primarily performed by rRNAs. At the RNA level, oocyte-specific 5S
rRNAs are long known for Xenopus. Recently, we described for zebrafish a similar
system in which the sole maternal-type 5S rRNA present in eggs is replaced
completely during embryonic development by a somatic-type. Here, we report the
discovery of an analogous system for the 45S rDNA elements: 5.8S, 18S, and 28S.
The maternal-type 5.8S, 18S, and 28S rRNA sequences differ substantially from
those of the somatic-type, plus the maternal-type rRNAs are also replaced by the
somatic-type rRNAs during embryogenesis. We discuss the structural and functional
implications of the observed sequence differences with respect to the
translational functions of the 5.8S, 18S, and 28S rRNA elements. Finally, in
silico evidence suggests that expansion segments (ES) in 18S rRNA, previously
implicated in ribosome-mRNA interaction, may have a preference for interacting
with specific mRNA genes. Taken together, our findings indicate that two distinct
types of ribosomes exist in zebrafish during development, each likely conducting
the translation machinery in a unique way.
PMID- 28500255
TI - Balancing Bleeding and Clotting: The Known Unknowns of Mechanically Assisted
Circulation.
PMID- 28500253
TI - LINC00341 exerts an anti-inflammatory effect on endothelial cells by repressing
VCAM1.
AB - The long noncoding RNAs (lncRNAs), which constitute a large portion of the
transcriptome, have gained intense research interest because of their roles in
regulating physiological and pathophysiological functions in the cell. We
identified from RNA-Seq profiling a set of lncRNAs in cultured human umbilical
vein endothelial cells (HUVECs) that are differentially regulated by
atheroprotective vs. atheroprone shear flows. Among the comprehensively annotated
lncRNAs, including both known and novel transcripts, LINC00341 is one of the most
abundant lncRNAs in endothelial cells. Moreover, its expression level is enhanced
by atheroprotective pulsatile shear flow and atorvastatin. Overexpression of
LINC00341 suppresses the expression of vascular cell adhesion molecule 1 (VCAM1)
and the adhesion of monocytes induced by atheroprone flow and tumor necrosis
factor-alpha. Underlying this anti-inflammatory role, LINC00341 guides enhancer
of zest homolog 2, a core histone methyltransferase of polycomb repressive
complex 2, to the promoter region of the VCAM1 gene to suppress VCAM1. Network
analysis reveals that the key signaling pathways (e.g., Rho and PI3K/AKT) are co
regulated with LINC00341 in endothelial cells in response to pulsatile shear.
Together, these findings suggest that LINC00341, as an example of lncRNAs, plays
important roles in modulating endothelial function in health and disease.
PMID- 28500256
TI - TZAP-ing telomeres down to size.
AB - The phenomenon of gradual telomere shortening has become a paradigm for how we
understand the biology of aging and cancer. Cell proliferation is accompanied by
cumulative telomere loss, and the aged cell either senesces, dies or transforms
toward cancer. This transformation requires the activation of telomere elongation
mechanisms in order to restore telomere length such that cell death or senescence
programs are not induced. Most of the time, this occurs through telomerase
reactivation. In other rare cases, the Alternative lengthening of telomeres (ALT)
pathway hijacks DNA recombination-associated mechanisms to hyperextend telomeres,
often to more than 50 kb. Why telomere length is restricted and what sets their
maximal length has been a long-standing puzzle in cell biology. Two recent
studies published in this issue of EMBO Reports [1] and recently in Science [2]
sought to address this important question. Both built on omics approaches that
identified ZBTB48 as a potential telomere-associated protein and reveal it to be
a critical regulator of telomere length homeostasis by the telomere trimming
mechanism. These discoveries provide fundamental insights for our understanding
of telomere trimming and how it impacts telomere integrity in stem and cancer
cells.
PMID- 28500254
TI - Increased Thromboembolic Events With Dabigatran Compared With Vitamin K
Antagonism in Left Ventricular Assist Device Patients: A Randomized Controlled
Pilot Trial.
AB - BACKGROUND: Left ventricular assist device-supported patients are usually
anticoagulated with a combination of aspirin and vitamin K antagonists. Long-term
vitamin K antagonist therapy can be complicated by unstable international
normalized ratio values and patient-related compliance problems. Therefore,
direct thrombin inhibitors may represent an alternative to vitamin K antagonists.
METHODS AND RESULTS: Thirty HeartWare ventricular assist device patients with
stable renal function were planned for this prospective, randomized, open-label,
single-center study. Patients were randomized to receive either phenprocoumon or
dabigatran in addition to aspirin for long-term anticoagulation. Treatment
duration was scheduled for 1 year and stopped after observation of a primary end
point. Dabigatran dose was 110 and 75 mg BID in patients with normal or impaired
renal function (glomerular filtration rate >80 mL/min or between 80 and 30
mL/min, respectively). The study was stopped prematurely for safety reasons after
16 patients (61+/-8 years, 1 female) were randomized. Thromboembolic events
occurred in 4 subjects receiving dabigatran (50%) and in 1 receiving
phenprocoumon (13%; P=0.28). No major bleeding was recorded, and no patient died
during the study. Median time to treatment termination was significantly shorter
in dabigatran patients (8.5 versus 12.0 months; P=0.015). CONCLUSIONS:
Thromboembolic events on dabigatran led to early termination of a randomized
controlled trial of dabigatran versus phenprocoumon in left ventricular assist
device patients. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov.
Unique identifier: NCT02872649.
PMID- 28500259
TI - Central serous chorioretinopathy secondary to tuberculosis: cause or coincidence.
AB - 32-year-old male with diagnosis of central serous chorioretinopathy (CSCR) in
both eyes and negative history of administration of any medicine was treated with
bilateral focal laser at leakage point, with visual recovery. Recurrence occurred
after 2 years in right eye and was treated successfully with acetazolamide.
Second recurrence occurred after 1 year. Acetazolamide was restarted, but no
improvement was noted. Thorough re-evaluation of the patient revealed a family
history of tuberculosis. Ancillary investigations rendered the presumptive
diagnosis of tuberculosis, and antituberculosis treatment led to visual recovery
with no recurrences. Present case poses two dilemmas: whether CSCR was secondary
to tuberculosis or was it an incidental association in tuberculosis endemic
population and second whether resolution occurred due to the treatment of
tuberculosis or due to mineralo-corticoid antagonism action of rifampicin.
Significance of patient's history, clinical observation and angiographic studies
in the diagnosis of idiopathic and recurrent CSCR is reiterated.
PMID- 28500257
TI - ZBTB48 is both a vertebrate telomere-binding protein and a transcriptional
activator.
AB - Telomeres constitute the ends of linear chromosomes and together with the
shelterin complex form a structure essential for genome maintenance and
stability. In addition to the constitutive binding of the shelterin complex,
other direct, yet more transient interactions are mediated by the CST complex and
HOT1/HMBOX1, while subtelomeric variant repeats are recognized by NR2C/F
transcription factors. Recently, the Kruppel-like zinc finger protein
ZBTB48/HKR3/TZAP has been described as a novel telomere-associated factor in the
vertebrate lineage. Here, we show that ZBTB48 binds directly both to telomeric
and to subtelomeric variant repeat sequences. ZBTB48 is found at telomeres of
human cancer cells regardless of the mode of telomere maintenance and it acts as
a negative regulator of telomere length. In addition to its telomeric function,
we demonstrate through a combination of RNAseq, ChIPseq and expression proteomics
experiments that ZBTB48 acts as a transcriptional activator on a small set of
target genes, including mitochondrial fission process 1 (MTFP1). This discovery
places ZBTB48 at the interface of telomere length regulation, transcriptional
control and mitochondrial metabolism.
PMID- 28500260
TI - Anticoagulation therapy for thromboembolism prevention: a case of warfarin
induced skin necrosis in the setting of protein C deficiency.
AB - Patients with protein C deficiency are at increased risk for thrombolic diseases.
Non-vitamin K antagonist anticoagulant options should be considered in patients
with warfarin-induced skin necrosis (WISN) in the setting of protein C. We report
a 41-year-old African American male patient with WISN and protein C deficiency
who was treated with rivaroxaban followed by dabigatran. After 1 month on
rivaroxaban, he began experiencing blood in his stools, unrelenting pain in his
lower extremities, found it difficult to obtain medication despite having
insurance and as a result did not maintain compliance. He was then assessed at
the hospital, symptomatically treated and discharged on dabigatran. After 6
weeks, he reported symptomatic relief and less side effects. This case involved a
head-to-head clinical comparison of rivaroxaban and dabigatran as alternatives to
warfarin anticoagulation therapy.
PMID- 28500261
TI - Osmotic demyelination syndrome in type 1 diabetes in the absence of
dyselectrolytaemia: an overlooked complication?
AB - Central pontine myelinolysis (CPM) is a demyelinating disorder of central nervous
system which involves central portion of the pons and sometimes extrapontine
areas also. It is commonly reported in settings of hyponatraemia or its rapid
correction, but in the last few years it has also been reported in patients with
diabetes in the absence of electrolyte disturbances or correction of serum
osmolality. Here we report a case of a 20-year-old female patient, with a known
history of type 1 diabetes mellitus, who presented with acute onset spastic
quadriparesis with dysarthria and mild ataxia which evolved over 2 weeks. Her MRI
brain showed well-defined, bilateral symmetric hyperintense lesion involving
central pons showing area of diffusion restriction which was consistent with CPM.
Patient was treated conservatively and improved over a period of few weeks. To
diagnose more number of cases, we should not overlook CPM in patients with
diabetes.
PMID- 28500258
TI - Transposon-driven transcription is a conserved feature of vertebrate
spermatogenesis and transcript evolution.
AB - Spermatogenesis is associated with major and unique changes to chromosomes and
chromatin. Here, we sought to understand the impact of these changes on
spermatogenic transcriptomes. We show that long terminal repeats (LTRs) of
specific mouse endogenous retroviruses (ERVs) drive the expression of many long
non-coding transcripts (lncRNA). This process occurs post-mitotically
predominantly in spermatocytes and round spermatids. We demonstrate that this
transposon-driven lncRNA expression is a conserved feature of vertebrate
spermatogenesis. We propose that transposon promoters are a mechanism by which
the genome can explore novel transcriptional substrates, increasing evolutionary
plasticity and allowing for the genesis of novel coding and non-coding genes.
Accordingly, we show that a small fraction of these novel ERV-driven transcripts
encode short open reading frames that produce detectable peptides. Finally, we
find that distinct ERV elements from the same subfamilies act as differentially
activated promoters in a tissue-specific context. In summary, we demonstrate that
LTRs can act as tissue-specific promoters and contribute to post-mitotic
spermatogenic transcriptome diversity.
PMID- 28500262
TI - Recurrent syncope in systemic lupus erythematosus: a hidden cause in abdomen.
AB - Systemic inflammatory rheumatic diseases have shown an increase in frequency of
internal malignancies, predominantly lymphoproliferative disorders. Occurrence of
solid organ tumours is exceedingly rare. It is even rarer for it to manifest as
recurrent syncope. We report a 55-year-old woman with systemic lupus
erythematosus, who later developed episodes of syncope and dizziness along with
diaphoresis and palpitations. She also had associated abdominal pain and
vomiting. Imaging revealed a gall bladder (GB) mass with hepatic extension, which
was histologically consistent with adenocarcinoma of the GB. Subsequently she
succumbed to death during chemotherapy.
PMID- 28500263
TI - Migration of eroded laparoscopic adjustable gastric band causing small bowel
obstruction and perforation.
AB - We present an unusual and rare complication caused by gastric band erosion into
the stomach after band placement 15 years ago. The complication was only picked
up after the band had subsequently migrated from the stomach at the site of
erosion, to the distal ileum causing acute small bowel obstruction and focal
perforation requiring emergency laparotomy.Abdominal pain in patients with
gastric band should always be treated as serious until proven otherwise.
PMID- 28500264
TI - S1P receptor 1-Mediated Anti-Renin-Angiotensin System Cardioprotection: Pivotal
Role of Mast Cell Aldehyde Dehydrogenase Type 2.
AB - In the ischemic-reperfused (I/R) heart, renin-containing mast cells (MC) release
enzymatically active renin, activating a local renin-angiotensin system (RAS),
causing excessive norepinephrine release and arrhythmic dysfunction. Activation
of Gi-receptors on MC and/or ischemic preconditioning (IPC) prevent renin
release, thus providing anti-RAS cardioprotection. We questioned whether
sphingosine-1-phosphate (S1P), a sphingolipid produced in the I/R heart, might
afford anti-RAS cardioprotection by activating Gi-coupled S1P1 receptors (S1P1R)
on MC. We report that activation of Gi-coupled S1P1R in cardiac MC confers IPC
like anti-RAS cardioprotection due to S1P1R-mediated inhibition of I/R-induced
cardiac MC degranulation and renin release. This results from an initial
translocation of protein kinase C subtype-epsilon and subsequent activation of
aldehyde dehydrogenase type 2 (ALDH2), culminating in the elimination of the MC
degranulating effects of acetaldehyde and other toxic species produced during
I/R. Inhibition of toxic aldehydes-induced MC-renin release prevents local RAS
activation, reduces infarct size, and alleviates arrhythmias. Notably, these
cardioprotective effects are lacking in hearts and MC from gene-targeted knock-in
mice (ALDH2*2) in which ALDH2 enzymatic activity is maximally reduced. Thus,
ALDH2 appears to play a pivotal role in this protective process. Our findings
suggest that MC S1P1R may represent a new pharmacologic and therapeutic target
for the direct alleviation of RAS-induced cardiac dysfunctions, including
ischemic heart disease and congestive heart failure.
PMID- 28500265
TI - Acyl-CoA-Binding Protein ACBP1 Modulates Sterol Synthesis during Embryogenesis.
AB - Fatty acids (FAs) and sterols are primary metabolites that exert interrelated
functions as structural and signaling lipids. Despite their common syntheses from
acetyl-coenzyme A, homeostatic cross talk remains enigmatic. Six Arabidopsis
(Arabidopsis thaliana) acyl-coenzyme A-binding proteins (ACBPs) are involved in
FA metabolism. ACBP1 interacts with PHOSPHOLIPASE Dalpha1 and regulates
phospholipid composition. Here, its specific role in the negative modulation of
sterol synthesis during embryogenesis is reported. ACBP1, likely in a liganded
state, interacts with STEROL C4-METHYL OXIDASE1-1 (SMO1-1), a rate-limiting
enzyme in the sterol pathway. Proembryo abortion in the double mutant indicated
that the ACBP1-SMO1-1 interaction is synthetic lethal, corroborating with their
strong promoter activities in developing ovules. Gas chromatography-mass
spectrometry revealed quantitative and compositional changes in FAs and sterols
upon overexpression or mutation of ACBP1 and/or SMO1-1 Aberrant levels of these
metabolites may account for the downstream defect in lipid signaling. GLABRA2
(GL2), encoding a phospholipid/sterol-binding homeodomain transcription factor,
was up-regulated in developing seeds of acbp1, smo1-1, and ACBP1+/-smo1-1 in
comparison with the wild type. Consistent with the corresponding transcriptional
alteration of GL2 targets, high-oil, low-mucilage phenotypes of gl2 were
phenocopied in ACBP1+/-smo1-1 Thus, ACBP1 appears to modulate the metabolism of
two important lipid classes (FAs and sterols) influencing cellular signaling.
PMID- 28500266
TI - NADPH Thioredoxin Reductase C and Thioredoxins Act Concertedly in Seedling
Development.
AB - Thiol-dependent redox regulation of enzyme activity plays a central role in the
rapid acclimation of chloroplast metabolism to ever-fluctuating light
availability. This regulatory mechanism relies on ferredoxin reduced by the
photosynthetic electron transport chain, which fuels reducing power to
thioredoxins (Trxs) via a ferredoxin-dependent Trx reductase. In addition,
chloroplasts harbor an NADPH-dependent Trx reductase, which has a joint Trx
domain at the carboxyl terminus, termed NTRC. Thus, a relevant issue concerning
chloroplast function is to establish the relationship between these two redox
systems and its impact on plant development. To address this issue, we generated
Arabidopsis (Arabidopsis thaliana) mutants combining the deficiency of NTRC with
those of Trxs f, which participate in metabolic redox regulation, and that of Trx
x, which has antioxidant function. The ntrc-trxf1f2 and, to a lower extent, ntrc
trxx mutants showed severe growth-retarded phenotypes, decreased photosynthesis
performance, and almost abolished light-dependent reduction of fructose-1,6
bisphosphatase. Moreover, the combined deficiency of both redox systems provokes
aberrant chloroplast ultrastructure. Remarkably, both the ntrc-trxf1f2 and ntrc
trxx mutants showed high mortality at the seedling stage, which was overcome by
the addition of an exogenous carbon source. Based on these results, we propose
that NTRC plays a pivotal role in chloroplast redox regulation, being necessary
for the activity of diverse Trxs with unrelated functions. The interaction
between the two thiol redox systems is indispensable to sustain photosynthesis
performed by cotyledons chloroplasts, which is essential for early plant
development.
PMID- 28500267
TI - Impaired Mitochondrial Transcription Termination Disrupts the Stromal Redox Poise
in Chlamydomonas.
AB - In photosynthetic eukaryotes, the metabolite exchange between chloroplast and
mitochondria ensures efficient photosynthesis under saturating light conditions.
The Chlamydomonas reinhardtii mutant stm6 is devoid of the mitochondrial
transcription termination factor MOC1 and aberrantly expresses the mitochondrial
genome, resulting in enhanced photosynthetic hydrogen production and diminished
light tolerance. We analyzed the modulation of mitochondrial and
chlororespiration during the acclimation of stm6 and the MOC1-complemented strain
to excess light. Although light stress stimulated mitochondrial respiration via
the energy-conserving cytochrome c pathway in both strains, the mutant was unable
to fine-tune the expression and activity of oxidative phosphorylation complex I
in excess light, which was accompanied by an increased mitochondrial respiration
via the alternative oxidase pathway. Furthermore, stm6 failed to fully activate
chlororespiration and cyclic electron flow due to a more oxidized state of the
chloroplast stroma, which is caused by an increased mitochondrial electron sink
capacity. Increased susceptibility to photoinhibition of PSII in stm6
demonstrates that the MOC1-dependent modulation of mitochondrial respiration
helps control the stromal redox poise as a crucial part of high-light acclimation
in C. reinhardtii.
PMID- 28500269
TI - Dynamic Cytology and Transcriptional Regulation of Rice Lamina Joint Development.
AB - Rice (Oryza sativa) leaf angle is determined by lamina joint and is an important
agricultural trait determining leaf erectness and, hence, the photosynthesis
efficiency and grain yield. Genetic studies reveal a complex regulatory network
of lamina joint development; however, the morphological changes, cytological
transitions, and underlying transcriptional programming remain to be elucidated.
A systemic morphological and cytological study reveals a dynamic developmental
process and suggests a common but distinct regulation of the lamina joint.
Successive and sequential cell division and expansion, cell wall thickening, and
programmed cell death at the adaxial or abaxial sides form the cytological basis
of the lamina joint, and the increased leaf angle results from the asymmetric
cell proliferation and elongation. Analysis of the gene expression profiles at
four distinct developmental stages ranging from initiation to senescence showed
that genes related to cell division and growth, hormone synthesis and signaling,
transcription (transcription factors), and protein phosphorylation (protein
kinases) exhibit distinct spatiotemporal patterns during lamina joint
development. Phytohormones play crucial roles by promoting cell differentiation
and growth at early stages or regulating the maturation and senescence at later
stages, which is consistent with the quantitative analysis of hormones at
different stages. Further comparison with the gene expression profile of leaf
inclination1, a mutant with decreased auxin and increased leaf angle, indicates
the coordinated effects of hormones in regulating lamina joint. These results
reveal a dynamic cytology of rice lamina joint that is fine-regulated by multiple
factors, providing informative clues for illustrating the regulatory mechanisms
of leaf angle and plant architecture.
PMID- 28500268
TI - A Rice NAC Transcription Factor Promotes Leaf Senescence via ABA Biosynthesis.
AB - It is well known that abscisic acid (ABA)-induced leaf senescence and premature
leaf senescence negatively affect the yield of rice (Oryza sativa). However, the
molecular mechanism underlying this relationship, especially the upstream
transcriptional network that modulates ABA level during leaf senescence, remains
largely unknown. Here, we demonstrate a rice NAC transcription factor, OsNAC2,
that participates in ABA-induced leaf senescence. Overexpression of OsNAC2
dramatically accelerated leaf senescence, whereas its knockdown lines showed a
delay in leaf senescence. Chromatin immunoprecipitation-quantitative PCR, dual
luciferase, and yeast one-hybrid assays demonstrated that OsNAC2 directly
activates expression of chlorophyll degradation genes, OsSGR and OsNYC3 Moreover,
ectopic expression of OsNAC2 leads to an increase in ABA levels via directly up
regulating expression of ABA biosynthetic genes (OsNCED3 and OsZEP1) as well as
down-regulating the ABA catabolic gene (OsABA8ox1). Interestingly, OsNAC2 is
upregulated by a lower level of ABA but downregulated by a higher level of ABA,
indicating a feedback repression of OsNAC2 by ABA. Additionally, reduced OsNAC2
expression leads to about 10% increase in the grain yield of RNAi lines. The
novel ABA-NAC-SAGs regulatory module might provide a new insight into the
molecular action of ABA to enhance leaf senescence and elucidates the
transcriptional network of ABA production during leaf senescence in rice.
PMID- 28500270
TI - Heavy Metals Induce Iron Deficiency Responses at Different Hierarchic and
Regulatory Levels.
AB - In plants, the excess of several heavy metals mimics iron (Fe) deficiency-induced
chlorosis, indicating a disturbance in Fe homeostasis. To examine the level at
which heavy metals interfere with Fe deficiency responses, we carried out an in
depth characterization of Fe-related physiological, regulatory, and morphological
responses in Arabidopsis (Arabidopsis thaliana) exposed to heavy metals. Enhanced
zinc (Zn) uptake closely mimicked Fe deficiency by leading to low chlorophyll but
high ferric-chelate reductase activity and coumarin release. These responses were
not caused by Zn-inhibited Fe uptake via IRON-REGULATED TRANSPORTER (IRT1).
Instead, Zn simulated the transcriptional response of typical Fe-regulated genes,
indicating that Zn affects Fe homeostasis at the level of Fe sensing. Excess
supplies of cobalt and nickel altered root traits in a different way from Fe
deficiency, inducing only transient Fe deficiency responses, which were
characterized by a lack of induction of the ethylene pathway. Cadmium showed a
rather inconsistent influence on Fe deficiency responses at multiple levels. By
contrast, manganese evoked weak Fe deficiency responses in wild-type plants but
strongly exacerbated chlorosis in irt1 plants, indicating that manganese
antagonized Fe mainly at the level of transport. These results show that the
investigated heavy metals modulate Fe deficiency responses at different
hierarchic and regulatory levels and that the interaction of metals with
physiological and morphological Fe deficiency responses is uncoupled. Thus, this
study not only emphasizes the importance of assessing heavy metal toxicities at
multiple levels but also provides a new perspective on how Fe deficiency
contributes to the toxic action of individual heavy metals.
PMID- 28500271
TI - Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart
Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus: A Mendelian Randomization
Analysis.
AB - BACKGROUND: The implications of different adiposity measures on cardiovascular
disease etiology remain unclear. In this article, we quantify and contrast causal
associations of central adiposity (waist-to-hip ratio adjusted for body mass
index [WHRadjBMI]) and general adiposity (body mass index [BMI]) with
cardiometabolic disease. METHODS: Ninety-seven independent single-nucleotide
polymorphisms for BMI and 49 single-nucleotide polymorphisms for WHRadjBMI were
used to conduct Mendelian randomization analyses in 14 prospective studies
supplemented with coronary heart disease (CHD) data from CARDIoGRAMplusC4D
(Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM]
plus The Coronary Artery Disease [C4D] Genetics; combined total 66 842 cases),
stroke from METASTROKE (12 389 ischemic stroke cases), type 2 diabetes mellitus
from DIAGRAM (Diabetes Genetics Replication and Meta-analysis; 34 840 cases), and
lipids from GLGC (Global Lipids Genetic Consortium; 213 500 participants)
consortia. Primary outcomes were CHD, type 2 diabetes mellitus, and major stroke
subtypes; secondary analyses included 18 cardiometabolic traits. RESULTS: Each
one standard deviation (SD) higher WHRadjBMI (1 SD~0.08 U) associated with a 48%
excess risk of CHD (odds ratio [OR] for CHD, 1.48; 95% confidence interval [CI],
1.28-1.71), similar to findings for BMI (1 SD~4.6 kg/m2; OR for CHD, 1.36; 95%
CI, 1.22-1.52). Only WHRadjBMI increased risk of ischemic stroke (OR, 1.32; 95%
CI, 1.03-1.70). For type 2 diabetes mellitus, both measures had large effects:
OR, 1.82 (95% CI, 1.38-2.42) and OR, 1.98 (95% CI, 1.41-2.78) per 1 SD higher
WHRadjBMI and BMI, respectively. Both WHRadjBMI and BMI were associated with
higher left ventricular hypertrophy, glycemic traits, interleukin 6, and
circulating lipids. WHRadjBMI was also associated with higher carotid intima
media thickness (39%; 95% CI, 9%-77% per 1 SD). CONCLUSIONS: Both general and
central adiposity have causal effects on CHD and type 2 diabetes mellitus.
Central adiposity may have a stronger effect on stroke risk. Future estimates of
the burden of adiposity on health should include measures of central and general
adiposity.
PMID- 28500273
TI - Fundamental trade-offs between information flow in single cells and cellular
populations.
AB - Signal transduction networks allow eukaryotic cells to make decisions based on
information about intracellular state and the environment. Biochemical noise
significantly diminishes the fidelity of signaling: networks examined to date
seem to transmit less than 1 bit of information. It is unclear how networks that
control critical cell-fate decisions (e.g., cell division and apoptosis) can
function with such low levels of information transfer. Here, we use theory,
experiments, and numerical analysis to demonstrate an inherent trade-off between
the information transferred in individual cells and the information available to
control population-level responses. Noise in receptor-mediated apoptosis reduces
information transfer to approximately 1 bit at the single-cell level but allows 3
4 bits of information to be transmitted at the population level. For processes
such as eukaryotic chemotaxis, in which single cells are the functional unit, we
find high levels of information transmission at a single-cell level. Thus, low
levels of information transfer are unlikely to represent a physical limit.
Instead, we propose that signaling networks exploit noise at the single-cell
level to increase population-level information transfer, allowing extracellular
ligands, whose levels are also subject to noise, to incrementally regulate
phenotypic changes. This is particularly critical for discrete changes in fate
(e.g., life vs. death) for which the key variable is the fraction of cells
engaged. Our findings provide a framework for rationalizing the high levels of
noise in metazoan signaling networks and have implications for the development of
drugs that target these networks in the treatment of cancer and other diseases.
PMID- 28500272
TI - Probing the lithium-response pathway in hiPSCs implicates the phosphoregulatory
set-point for a cytoskeletal modulator in bipolar pathogenesis.
AB - The molecular pathogenesis of bipolar disorder (BPD) is poorly understood. Using
human-induced pluripotent stem cells (hiPSCs) to unravel such mechanisms in
polygenic diseases is generally challenging. However, hiPSCs from BPD patients
responsive to lithium offered unique opportunities to discern lithium's target
and hence gain molecular insight into BPD. By profiling the proteomics of BDP
hiPSC-derived neurons, we found that lithium alters the phosphorylation state of
collapsin response mediator protein-2 (CRMP2). Active nonphosphorylated CRMP2,
which binds cytoskeleton, is present throughout the neuron; inactive
phosphorylated CRMP2, which dissociates from cytoskeleton, exits dendritic
spines. CRMP2 elimination yields aberrant dendritogenesis with diminished spine
density and lost lithium responsiveness (LiR). The "set-point" for the ratio of
pCRMP2:CRMP2 is elevated uniquely in hiPSC-derived neurons from LiR BPD patients,
but not with other psychiatric (including lithium-nonresponsive BPD) and
neurological disorders. Lithium (and other pathway modulators) lowers pCRMP2,
increasing spine area and density. Human BPD brains show similarly elevated
ratios and diminished spine densities; lithium therapy normalizes the ratios and
spines. Consistent with such "spine-opathies," human LiR BPD neurons with
abnormal ratios evince abnormally steep slopes for calcium flux; lithium
normalizes both. Behaviorally, transgenic mice that reproduce lithium's
postulated site-of-action in dephosphorylating CRMP2 emulate LiR in BPD. These
data suggest that the "lithium response pathway" in BPD governs CRMP2's
phosphorylation, which regulates cytoskeletal organization, particularly in
spines, modulating neural networks. Aberrations in the posttranslational
regulation of this developmentally critical molecule may underlie LiR BPD
pathogenesis. Instructively, examining the proteomic profile in hiPSCs of a
functional agent-even one whose mechanism-of-action is unknown-might reveal
otherwise inscrutable intracellular pathogenic pathways.
PMID- 28500277
TI - Ba/F3 transformation assays.
PMID- 28500274
TI - Combined HMG-COA reductase and prenylation inhibition in treatment of CCM.
AB - Cerebral cavernous malformations (CCMs) are common vascular anomalies that
develop in the central nervous system and, more rarely, the retina. The lesions
can cause headache, seizures, focal neurological deficits, and hemorrhagic
stroke. Symptomatic lesions are treated according to their presentation; however,
targeted pharmacological therapies that improve the outcome of CCM disease are
currently lacking. We performed a high-throughput screen to identify Food and
Drug Administration-approved drugs or other bioactive compounds that could
effectively suppress hyperproliferation of mouse brain primary astrocytes
deficient for CCM3. We demonstrate that fluvastatin, an inhibitor of 3-hydroxy-3
methyl-glutaryl (HMG)-CoA reductase and the N-bisphosphonate zoledronic acid
monohydrate, an inhibitor of protein prenylation, act synergistically to reverse
outcomes of CCM3 loss in cultured mouse primary astrocytes and in Drosophila
glial cells in vivo. Further, the two drugs effectively attenuate neural and
vascular deficits in chronic and acute mouse models of CCM3 loss in vivo,
significantly reducing lesion burden and extending longevity. Sustained
inhibition of the mevalonate pathway represents a potential pharmacological
treatment option and suggests advantages of combination therapy for CCM disease.
PMID- 28500275
TI - Experimental evaluation of the generalized vibrational theory of G protein
coupled receptor activation.
AB - Recently, an alternative theory concerning the method by which olfactory proteins
are activated has garnered attention. This theory proposes that the activation of
olfactory G protein-coupled receptors occurs by an inelastic electron tunneling
mechanism that is mediated through the presence of an agonist with an appropriate
vibrational state to accept the inelastic portion of the tunneling electron's
energy. In a recent series of papers, some suggestive theoretical evidence has
been offered that this theory may be applied to nonolfactory G protein-coupled
receptors (GPCRs), including those associated with the central nervous system
(CNS). [Chee HK, June OS (2013) Genomics Inform 11(4):282-288; Chee HK, et al.
(2015) FEBS Lett 589(4):548-552; Oh SJ (2012) Genomics Inform 10(2):128-132].
Herein, we test the viability of this idea, both by receptor affinity and
receptor activation measured by calcium flux. This test was performed using a
pair of well-characterized agonists for members of the 5-HT2 class of serotonin
receptors, 2,5-dimethoxy-4-iodoamphetamine (DOI) and N,N-dimethyllysergamide (DAM
57), and their respective deuterated isotopologues. No evidence was found that
selective deuteration affected either the binding affinity or the activation by
the selected ligands for the examined members of the 5-HT2 receptor class.
PMID- 28500278
TI - Comparison of Echocardiography and 64-Multislice Spiral Computed Tomography for
the Diagnosis of Pediatric Congenital Heart Disease.
AB - BACKGROUND The goals of this study were: to compare echocardiogram and 64
multislice spiral computed tomography (64-MSCT) in diagnosing pediatric
congenital heart disease; to determine the significance of ECHO for diagnosing
congenital heart disease; and to identify the appropriate diagnosis for
congenital heart disease through combined use of 64-MSCT and ECHO. MATERIAL AND
METHODS Thirty patients underwent both ECHO and 64-MSCT diagnoses before their
surgeries. Imaging from ECHO and 64-MSCT were analyzed by 4 specialists. The
diagnostic accuracy and kappa value of ECHO and 64-MSCT were evaluated based on
the operation results. The accuracy of the 2 methods was evaluated using the
McNemar chi2 test. RESULTS We confirmed 138 malformations in 30 children by
surgery. The diagnostic accuracy of ECHO and 64-MSCT was 98.40% and 96.20%,
respectively, with a significant difference between the 2 results (chi2=6.404,
P=0.011). We compared prognosis accuracy and uniformity on 3 types of congenital
heart disease (cardiac malformation, heart-large vascular connecting
malformation, and large vascular malformation): 56 cardiac malformations were
confirmed by surgery, in which the diagnostic accuracy of ECHO and 64-MSCT was
99.50% and 94.80%, respectively. (chi2=8.578, P=0.034); 31 heart-large vascular
connecting malformations were confirmed by surgery, in which the diagnostic
accuracy of ECHO and 64-MSCT was 99.00% and 95.42% (chi2=6.779, P=0.009); and 51
vascular malformations were confirmed, in which the diagnostic accuracy of ECHO
and 64-MSCT was 96.30% and 98.30% (chi2=1.806, P=0.179). CONCLUSIONS ECHO is more
effective than 64-MSCT in preoperative diagnosis of congenital heart disease,
especially for children.
PMID- 28500279
TI - New Navigation Surgery for Resection of Lymphatic Malformations Using Indocyanine
Green Fluorescence Imaging.
AB - BACKGROUND We used indocyanine green (ICG) fluorescence imaging to completely
resect lymphatic malformations (LMs). This is the first report of navigation
surgery utilizing ICG fluorescence imaging for resection of LMs. CASE REPORT A 15
year-old boy was diagnosed with LMs in the abdominal wall. The extent of the
tumor was determined by an ultrasound, and ICG (Diagnogreen(r), Daiichi-Sankyo
Pharma, Tokyo, Japan) was injected subcutaneously and intradermally into the core
and 2 marginal regions of the tumor (3 injections in total), respectively. During
surgery, the extent of the tumor was confirmed with a photodynamic eye, and the
tumor was completely resected. A fluorescent portion macroscopically estimated as
normal was additionally resected and no residual fluorescence or tumor were
confirmed in the remaining tissue. Abnormal lymphatic vessels were
histopathologically observed in the additionally resected tissue, indicating the
invasion of LMs. The surgery had a good outcome with no evidence of recurrence.
CONCLUSIONS We performed near-infrared fluorescence-guided imaging surgery for
the resection of LMs in the abdominal wall. This is a single case study;
therefore, assessment of more cases is warranted for further validation. This
procedure could provide significant benefit to patients requiring resection of
LMs.
PMID- 28500280
TI - Visualization of a Mammalian Mitochondrion by Coherent X-ray Diffractive Imaging.
AB - We report a three dimensional (3D) quantitative visualization of a mammalian
mitochondrion by coherent x-ray diffractive imaging (CXDI) using synchrotron
radiation. The internal structures of a mitochondrion from a mouse embryonic
fibroblast cell line (NIH3T3) were visualized by tomographic imaging at
approximately 60 nm resolution without the need for sectioning or staining. The
overall structure consisted of a high electron density region, composed of the
outer and inner membranes and the cristae cluster, which enclosed the lower
density mitochondrial matrix. The average mass density of the mitochondrion was
about 1.36 g/cm3. Sectioned images of the cristae reveal that they have neither a
baffle nor septa shape but were instead irregular. In addition, a high
resolution, about 14 nm, 2D projection image was captured of a similar
mitochondrion with the aid of strongly scattering Au reference objects. Obtaining
3D images at this improved resolution will allow CXDI to be an effective and
nondestructive method for investigating the innate structure of mitochondria and
other important life supporting organelles.
PMID- 28500281
TI - Layered social influence promotes multiculturality in the Axelrod model.
AB - Despite the presence of increasing pressure towards globalisation, the
coexistence of different cultures is a distinctive feature of human societies.
However, how multiculturality can emerge in a population of individuals inclined
to imitation, and how it remains stable under cultural drift, i.e. the
spontaneous mutation of traits in the population, still needs to be understood.
To solve such a problem, we propose here a microscopic model of culture
dissemination which takes into account that, in real social systems, the
interactions are organised in various layers corresponding to different interests
or topics. We show that the addition of multiplexity in the modeling of our
society generates qualitatively novel dynamical behavior, producing a new stable
regime of cultural diversity. This finding suggests that the layered organisation
of social influence typical of modern societies is the key ingredient to explain
why and how multiculturality emerges and thrives in our world.
PMID- 28500282
TI - The molecular basis of thin filament activation: from single molecule to muscle.
AB - For muscles to effectively power locomotion, trillions of myosin molecules must
rapidly attach and detach from the actin thin filament. This is accomplished by
precise regulation of the availability of the myosin binding sites on actin (i.e.
activation). Both calcium (Ca++) and myosin binding contribute to activation, but
both mechanisms are simultaneously active during contraction, making their
relative contributions difficult to determine. Further complicating the process,
myosin binding accelerates the attachment rate of neighboring myosin molecules,
adding a cooperative element to the activation process. To de-convolve these two
effects, we directly determined the effect of Ca++ on the rate of attachment of a
single myosin molecule to a single regulated actin thin filament, and separately
determined the distance over which myosin binding increases the attachment rate
of neighboring molecules. Ca++ alone increases myosin's attachment rate ~50-fold,
while myosin binding accelerates attachment of neighboring molecules 400 nm along
the actin thin filament.
PMID- 28500283
TI - Fine-tune regulation of carboxypeptidase N1 controls vascular patterning during
zebrafish development.
AB - Vascular development is regulated by complicated signals and molecules in
vertebrates. In this study, we characterized a novel function of carboxypeptidase
N1 (Cpn1) in the vasculature. We show that cpn1 mRNA is expressed in developing
vessels. The knockdown of cpn1 by morpholino injection impairs the growth of
intersegmental vessels (ISV) and caudal vein plexus (CVP), suggesting the role of
cpn1 in vascular development. We showed that vascular defects are not caused by
cell death but are due to the impairment of migration and proliferation.
Consistent with vascular growth defects, loss of cpn1 affects the expression of
the vascular markers flt4, mrc1, flk, stabilin, and ephrinb2. Furthermore, the
overexpression of cpn1 impaired the growth of ISV and CVP, but the remodeling
expression of vascular markers was different from the knockdown of cpn1,
indicating the differential regulation mechanisms in cpn1-overexpressing embryos.
We examine the interaction between cpn1 and multiple signals and observed that
cpn1 is regulated by Notch/VEGF signals for ISV growth and likely regulates BMP
signals for CVP patterning. In conclusion, we demonstrate that cpn1 has a
critical role in the vascular development of zebrafish. We also reveal a fine
tune regulation of cpn1 that controls vascular patterning mediated by multiple
signals.
PMID- 28500284
TI - Hotspot analyses indicate significant conservation gaps for evergreen broadleaved
woody plants in China.
AB - Evergreen broadleaved woody plants (EBWPs) are dominant components in forests and
savanna of the global tropic and subtropic regions. Southern China possesses the
largest continuous area of subtropical EBWPs distribution, harboring a high
proportion of endemic species. Hotspot and gap analyses are effective methods for
analyzing the spatial pattern of biodiversity and conservation and were used here
for EBWPs in China. Based on a distribution data set of 6,265 EBWPs with a
spatial resolution of 50 * 50 km, we measured diversity of EBWPs in China using
four indices: species richness, corrected weighted endemism, relative
phylogenetic diversity, and phylogenetic endemism. According to the results based
on 10% threshold, 15.73% of China's land area was identified as hotspots using at
least one diversity index. Only 2.14% of China's land area was identified as
hotspots for EBWPs by all four metrics simultaneously. Most of the hotspots
locate in southern mountains. Moreover, we found substantial conservation gaps
for Chinese EBWPs. Only 25.43% of the hotspots are covered by existing nature
reserves by more than 10% of their area. We suggest to promote the establishment
and management of nature reserve system within the hotspot gaps.
PMID- 28500285
TI - Topological Quantum Phase Transition and Local Topological Order in a Strongly
Interacting Light-Matter System.
AB - An attempt is made to understand the topological quantum phase transition,
emergence of relativistic modes and local topological order of light in a
strongly interacting light-matter system. We study this system, in a one
dimensional array of nonlinear cavities. Topological quantum phase transition
occurs with massless excitation only for the finite detuning process. We present
a few results based on the exact analytical calculations along with the physical
explanations. We observe the emergence of massive Majorana fermion mode at the
topological state, massless Majorana-Weyl fermion mode during the topological
quantum phase transition and Dirac fermion mode for the non-topological state.
Finally, we study the quantized Berry phase (topological order) and its
connection to the topological number (winding number).
PMID- 28500288
TI - Light perception in aerial tissues enhances DWF4 accumulation in root tips and
induces root growth.
AB - Many attempts have been made to characterize the activities of brassinosteroids
(BRs), which are important plant hormones. The crosstalk between light perception
and the BR signalling pathway has been extensively studied regarding its effects
on photomorphogenesis, especially in elongating etiolated hypocotyls. In
contrast, how and where the light induces BR biosynthesis remain uncharacterized.
DWF4 is one of the main enzymes involved in the BR biosynthesis pathway in
Arabidopsis thaliana. We established DWF4-GUS A. thaliana lines in a homozygous
dwf4-102 genetic background, but functionally complemented with a genomic DWF4
sequence fused in-frame with a beta-glucuronidase (GUS) marker gene. The DWF4-GUS
plants enabled the visualization of the accumulation of DWF4 under different
conditions. We investigated the effects of aboveground light on root and
hypocotyl growth. We observed that root length increased when shoots were
maintained under light irrespective of whether roots were exposed to light. We
also determined that light perception in aerial tissues enhanced DWF4
accumulation in the root tips. Overall, our data indicate that BR biosynthesis is
promoted in the root tip regions by an unknown mechanism in distantly located
shoot tissues exposed to light, leading to increased root growth.
PMID- 28500287
TI - Determination of nasal and oropharyngeal microbiomes in a multicenter population
based study - findings from Pretest 1 of the German National Cohort.
AB - We examined acceptability, preference and feasibility of collecting nasal and
oropharyngeal swabs, followed by microbiome analysis, in a population-based study
with 524 participants. Anterior nasal and oropharyngeal swabs were collected by
certified personnel. In addition, participants self-collected nasal swabs at home
four weeks later. Four swab types were compared regarding (1) participants'
satisfaction and acceptance and (2) detection of microbial community structures
based on deep sequencing of the 16 S rRNA gene V1-V2 variable regions. All
swabbing methods were highly accepted. Microbial community structure analysis
revealed 846 phylotypes, 46 of which were unique to oropharynx and 164 unique to
nares. The calcium alginate tipped swab was found unsuitable for microbiome
determinations. Among the remaining three swab types, there were no differences
in oropharyngeal microbiomes detected and only marginal differences in nasal
microbiomes. Microbial community structures did not differ between staff
collected and self-collected nasal swabs. These results suggest (1) that nasal
and oropharyngeal swabbing are highly feasible methods for human population-based
studies that include the characterization of microbial community structures in
these important ecological niches, and (2) that self-collection of nasal swabs at
home can be used to reduce cost and resources needed, particularly when serial
measurements are to be taken.
PMID- 28500286
TI - A-Kinase Anchoring Protein 79/150 Scaffolds Transient Receptor Potential A 1
Phosphorylation and Sensitization by Metabotropic Glutamate Receptor Activation.
AB - Mechanical pain serves as a base clinical symptom for many of the world's most
debilitating syndromes. Ion channels expressed by peripheral sensory neurons
largely contribute to mechanical hypersensitivity. Transient Receptor Potential A
1 (TRPA1) is a ligand-gated ion channel that contributes to inflammatory
mechanical hypersensitivity, yet little is known as to the post-translational
mechanism behind its somatosensitization. Here, we utilize biochemical,
electrophysiological, and behavioral measures to demonstrate that metabotropic
glutamate receptor-induced sensitization of TRPA1 nociceptors stimulates targeted
modification of the receptor. Type 1 mGluR5 activation increases TRPA1 receptor
agonist sensitivity in an AKA-dependent manner. As a scaffolding protein for
Protein Kinases A and C (PKA and PKC, respectively), AKAP facilitates
phosphorylation and sensitization of TRPA1 in ex vivo sensory neuronal
preparations. Furthermore, hyperalgesic priming of mechanical hypersensitivity
requires both TRPA1 and AKAP. Collectively, these results identify a novel AKAP
mediated biochemical mechanism that increases TRPA1 sensitivity in peripheral
sensory neurons, and likely contributes to persistent mechanical
hypersensitivity.
PMID- 28500289
TI - Stapled BIG3 helical peptide ERAP potentiates anti-tumour activity for breast
cancer therapeutics.
AB - Estradiol (E2) and the oestrogen receptor-alpha (ERalpha) signalling pathway play
pivotal roles in the proliferative activity of breast cancer cells. Recent
findings show that the brefeldin A-inhibited guanine nucleotide-exchange protein
3-prohibitin 2 (BIG3-PHB2) complex plays a crucial role in E2/ERalpha signalling
modulation in breast cancer cells. Moreover, specific inhibition of the BIG3-PHB2
interaction using the ERalpha activity-regulator synthetic peptide (ERAP: 165-177
amino acids), derived from alpha-helical BIG3 sequence, resulted in a significant
anti-tumour effect. However, the duration of this effect was very short for
viable clinical application. We developed the chemically modified ERAP using
stapling methods (stapledERAP) to improve the duration of its antitumour effects.
The stapledERAP specifically inhibited the BIG3-PHB2 interaction and exhibited
long-lasting suppressive activity. Its intracellular localization without the
membrane-permeable polyarginine sequence was possible via the formation of a
stable alpha-helix structure by stapling. Tumour bearing-mice treated daily or
weekly with stapledERAP effectively prevented the BIG3-PHB2 interaction, leading
to complete regression of E2-dependent tumours in vivo. Most importantly,
combination of stapledERAP with tamoxifen, fulvestrant, and everolimus caused
synergistic inhibitory effects on growth of breast cancer cells. Our findings
suggested that the stapled ERAP may be a promising anti-tumour drug to suppress
luminal-type breast cancer growth.
PMID- 28500290
TI - Impact of Hepatitis C Treatment as Prevention for People Who Inject Drugs is
sensitive to contact network structure.
AB - Treatment as Prevention (TasP) using directly-acting antivirals has been
advocated for Hepatitis C Virus (HCV) in people who inject drugs (PWID), but
treatment is expensive and TasP's effectiveness is uncertain. Previous modelling
has assumed a homogeneously-mixed population or a static network lacking turnover
in the population and injecting partnerships. We developed a transmission-dynamic
model on a dynamic network of injecting partnerships using data from survey of
injecting behaviour carried out in London, UK. We studied transmission on a novel
exponential-clustered network, as well as on two simpler networks for comparison,
an exponential unclustered and a random network, and found that TasP's
effectiveness differs markedly. With respect to an exponential-clustered network,
the random network (and homogeneously-mixed population) overestimate TasP's
effectiveness, whereas the exponential-unclustered network underestimates it. For
all network types TasP's effectiveness depends on whether treated patients change
risk behaviour, and on treatment coverage: higher coverage requires fewer total
treatments for the same health gain. Whilst TasP can greatly reduce HCV
prevalence, incidence of infection, and incidence of reinfection in PWID,
assessment of TasP's effectiveness needs to take account of the injecting
partnership network structure and post-treatment behaviour change, and further
empirical study is required.
PMID- 28500291
TI - The complete chloroplast genome sequence of tung tree (Vernicia fordii):
Organization and phylogenetic relationships with other angiosperms.
AB - Tung tree (Vernicia fordii) is an economically important tree widely cultivated
for industrial oil production in China. To better understand the molecular basis
of tung tree chloroplasts, we sequenced and characterized its genome using PacBio
RS II sequencing platforms. The chloroplast genome was sequenced with 161,528 bp
in length, composed with one pair of inverted repeats (IRs) of 26,819 bp, which
were separated by one small single copy (SSC; 18,758 bp) and one large single
copy (LSC; 89,132 bp). The genome contains 114 genes, coding for 81 protein, four
ribosomal RNAs and 29 transfer RNAs. An expansion with integration of an
additional rps19 gene in the IR regions was identified. Compared to the
chloroplast genome of Jatropha curcas, a species from the same family, the tung
tree chloroplast genome is distinct with 85 single nucleotide polymorphisms
(SNPs) and 82 indels. Phylogenetic analysis suggests that V. fordii is a sister
species with J. curcas within the Eurosids I. The nucleotide sequence provides
vital molecular information for understanding the biology of this important oil
tree.
PMID- 28500292
TI - Fitness estimates from experimental infections predict the long-term strain
structure of a vector-borne pathogen in the field.
AB - The populations of many pathogen species consist of a collection of common and
rare strains but the factors underlying this strain-specific variation in
frequency are often unknown. Understanding frequency variation among strains is
particularly challenging for vector-borne pathogens where the strain-specific
fitness depends on the performance in both the vertebrate host and the arthropod
vector. Two sympatric multiple-strain tick-borne pathogens, Borrelia afzelii and
B. garinii, that use the same tick vector, Ixodes ricinus, but different
vertebrate hosts were studied. 454-sequencing of the polymorphic ospC gene was
used to characterize the community of Borrelia strains in a local population of
I. ricinus ticks over a period of 11 years. Estimates of the reproduction number
(R0), a measure of fitness, were obtained for six strains of B. afzelii from a
previous laboratory study. There was substantial variation in prevalence among
strains and some strains were consistently common whereas other strains were
consistently rare. In B. afzelii, the strain-specific estimates of R0 in
laboratory mice explained over 70% of the variation in the prevalences of the
strains in our local population of ticks. Our study shows that laboratory
estimates of fitness can predict the community structure of multiple-strain
pathogens in the field.
PMID- 28500293
TI - Preparation of Nanowire like WSe2-Graphene Nanocomposite for Photocatalytic
Reduction of CO2 into CH3OH with the Presence of Sacrificial Agents.
AB - A nanowire-like WSe2-graphene catalyst was prepared via ultra-sonication and was
tested in terms of the photocatalytic reduction of CO2 into CH3OH under
irradiation with UV/visible light. The prepared nano-composite was further
characterized via XRD, SEM, TEM, Raman and XPS. The photocurrent analysis was
further tested for its photocatalytic reduction of CO2 using gas chromatography
(GCMS-QP2010 SE). To further improve the the photo-catalytic efficiency, a
sacrificial agent (Na2S/Na2SO3) was added to the WSe2-graphene nanocomposite and
was found to improve the photo-catalytic efficiency, with the methanol yield
reaching 5.0278 umol g-1h-1. Our present work provides a convenient way to
prepare nanomaterials various morphologies that have future applications for
environmental remediation.
PMID- 28500294
TI - Adipocyte Fatty-Acid Binding Protein is Overexpressed in Cirrhosis and Correlates
with Clinical Outcomes.
AB - Fatty-acid-binding proteins (FABPs) are small intracellular proteins that
coordinate lipid-mediated processes by targeting metabolic and immune response
pathways. The aim of the study was to investigate plasma FABPs levels and their
relationship with clinical outcomes in cirrhosis. Plasma levels of L-FABP1(liver
and kidney), I-FABP2(intestine), and A-FABP4(adipocyte and macrophages) were
measured in 274 patients with decompensated cirrhosis. Hepatic gene expression of
FABPs was assessed in liver biopsies from patients with decompensated cirrhosis
and in liver cell types from mice with cirrhosis. Immunohistochemistry of A-FABP4
in human liver biopsy was also performed. Plasma levels of FABPs were increased
in patients with decompensated cirrhosis compared to those of healthy subjects (L
FABP1: 25 (17-39) vs 10 (9-17) ng/mL p = 0.001, I-FABP2: 1.1 (0.5-2.1) vs 0.6
(0.4-1) ng/mL p = 0.04 and A-FABP4: 37 (20-68) vs 16 (11-33) ng/mL p = 0.002),
respectively. Increased A-FABP4 levels were associated with complications of
cirrhosis, acute-on-chronic liver failure and poor survival. Hepatic A-FABP4 gene
expression was upregulated in decompensated cirrhosis. Macrophages were the main
liver cell that over-expressed A-FABP4 in experimental cirrhosis and increased A
FABP4 was found in macrophages of human biopsies by immunohistochemistry. A-FABP4
levels are increased in decompensated cirrhosis and correlate with poor outcomes.
Liver macrophages appear to be the main source of A-FABP4 in decompensated
cirrhosis.
PMID- 28500297
TI - Three-dimensional quantitative fracture analysis of tight gas sandstones using
industrial computed tomography.
AB - Tight gas sandstone samples are imaged at high resolution industrial X-ray
computed tomography (ICT) systems to provide a three-dimensional quantitative
characterization of the fracture geometries. Fracture networks are quantitatively
analyzed using a combination of 2-D slice analysis and 3-D visualization and
counting. The core samples are firstly scanned to produce grayscale slices, and
the corresponding fracture area, length, aperture and fracture porosity as well
as fracture density were measured. Then the 2-D slices were stacked to create a
complete 3-D image using volume-rendering software. The open fractures (vug) are
colored cyan whereas the calcite-filled fractures (high density objects) are
colored magenta. The surface area and volume of both open fractures and high
density fractures are calculated by 3-D counting. Then the fracture porosity and
fracture aperture are estimated by 3-D counting. The fracture porosity and
aperture from ICT analysis performed at atmospheric pressure are higher than
those calculated from image logs at reservoir conditions. At last, the fracture
connectivity is determined through comparison of fracture parameters with
permeability. Distribution of fracture density and fracture aperture determines
the permeability and producibility of tight gas sandstones. ICT has the advantage
of performing three dimensional fracture imaging in a non-destructive way.
PMID- 28500296
TI - Digital Etch Technique for Forming Ultra-Scaled Germanium-Tin (Ge 1-x Sn x ) Fin
Structure.
AB - We developed a new digital etch process that allows precise etching of Germanium
or Germanium-tin (Ge1-x Sn x ) materials. The digital etch approach consists of
Ge1-x Sn x oxide formation by plasma oxidation and oxide removal in diluted
hydrochloric acid at room temperature. The first step is a self-limiting process,
as the thickness of oxide layer grows logarithmically with the oxidation time and
saturates fast. Consistent etch rates in each cycle were found on the Ge1-x Sn x
samples, with the surfaces remaining smooth after etch. The digital etch process
parameters were tuned to achieve various etch rates. By reducing the radio
frequency power to 70 W, etch rate of sub-1.2 nm was obtained on a Ge0.875Sn0.125
sample. The digital etch process was employed to fabricate the Ge1-x Sn x fin
structures. Extremely scaled Ge0.95Sn0.05 fins with 5 nm fin width were realized.
The side walls of the Ge0.95Sn0.05 fins are smooth, and no crystal damage can be
observed. This technique provides an option to realize aggressively scaled
nanostructure devices based on Ge1-x Sn x materials with high-precision control.
PMID- 28500295
TI - Angiotensin II type 1/adenosine A 2A receptor oligomers: a novel target for
tardive dyskinesia.
AB - Tardive dyskinesia (TD) is a serious motor side effect that may appear after long
term treatment with neuroleptics and mostly mediated by dopamine D2 receptors
(D2Rs). Striatal D2R functioning may be finely regulated by either adenosine A2A
receptor (A2AR) or angiotensin receptor type 1 (AT1R) through putative receptor
heteromers. Here, we examined whether A2AR and AT1R may oligomerize in the
striatum to synergistically modulate dopaminergic transmission. First, by using
bioluminescence resonance energy transfer, we demonstrated a physical AT1R-A2AR
interaction in cultured cells. Interestingly, by protein-protein docking and
molecular dynamics simulations, we described that a stable heterotetrameric
interaction may exist between AT1R and A2AR bound to antagonists (i.e. losartan
and istradefylline, respectively). Accordingly, we subsequently ascertained the
existence of AT1R/A2AR heteromers in the striatum by proximity ligation in situ
assay. Finally, we took advantage of a TD animal model, namely the reserpine
induced vacuous chewing movement (VCM), to evaluate a novel multimodal
pharmacological TD treatment approach based on targeting the AT1R/A2AR complex.
Thus, reserpinized mice were co-treated with sub-effective losartan and
istradefylline doses, which prompted a synergistic reduction in VCM. Overall, our
results demonstrated the existence of striatal AT1R/A2AR oligomers with potential
usefulness for the therapeutic management of TD.
PMID- 28500298
TI - ZBP1 phosphorylation at serine 181 regulates its dendritic transport and the
development of dendritic trees of hippocampal neurons.
AB - Local protein synthesis occurs in axons and dendrites of neurons, enabling fast
and spatially restricted responses to a dynamically changing extracellular
environment. Prior to local translation, mRNA that is to be translated is packed
into ribonucleoprotein particles (RNPs) where RNA binding proteins ensure mRNA
silencing and provide a link to molecular motors. ZBP1 is a component of RNP
transport particles and is known for its role in the local translation of beta
actin mRNA. Its binding to mRNA is regulated by tyrosine 396 phosphorylation, and
this particular modification was shown to be vital for axonal growth and
dendritic branching. Recently, additional phosphorylation of ZBP1 at serine 181
(Ser181) was described in non-neuronal cells. In the present study, we found that
ZBP1 is also phosphorylated at Ser181 in neurons in a mammalian/mechanistic
target of rapamycin complex 2-, Src kinase-, and mRNA binding-dependent manner.
Furthermore, Ser181 ZBP1 phosphorylation was essential for the proper dendritic
branching of hippocampal neurons that were cultured in vitro and for the proper
ZBP1 dendritic distribution and motility.
PMID- 28500299
TI - Visual processing mode switching regulated by VIP cells.
AB - The responses of neurons in mouse primary visual cortex (V1) to visual stimuli
depend on behavioral states. Specifically, surround suppression is reduced during
locomotion. Although locomotion-induced vasoactive intestinal polypeptide
positive (VIP) interneuron depolarization can account for the reduction of
surround suppression, the functions of VIP cell depolarization are not fully
understood. Here we utilize a firing rate model and a computational model to
elucidate the potential functions of VIP cell depolarization during locomotion.
Our analyses suggest 1) that surround suppression sharpens the visual responses
in V1 to a stationary scene, 2) that depolarized VIP cells enhance V1 responses
to moving objects by reducing self-induced surround suppression and 3) that
during locomotion V1 neuron responses to some features of the moving objects can
be selectively enhanced. Thus, VIP cells regulate surround suppression to allow
pyramidal neurons to optimally encode visual information independent of
behavioral state.
PMID- 28500300
TI - Alterations of cerebral perfusion in asymptomatic internal carotid artery steno
occlusive disease.
AB - Patients with asymptomatic occlusion in the internal carotid arteries (ICA) have
been shown to have a better preserved hemodynamic status of the brain as compared
to patients with symptoms. This study was aimed to explore the cerebral perfusion
alterations in asymptomatic patients using multi-parametric arterial spin
labeling (ASL) magnetic resonance (MR) imaging. Forty-two patients diagnosed with
asymptomatic ICA stenosis/occlusion were prospectively included and divided into
high-grade (ultrasonographic stenosis >=70%, N = 20) and low-grade groups (N =
22). On a 3-Tesla clinical MR scanner, pseudo-continuous ASL was performed to
measure cerebral blood flow CBF, arterial transit time ATT, and flow territory.
Fisher's exact test indicates that the high-grade group has higher frequency in
asymmetric ATT (p < 10-3) and asymmetric flow territory (p < 10-3) as compared to
the low-grade group. The between-group difference in CBF asymmetry is marginal (p
= 0.062). Logistic regression further reveals that hemispherical asymmetry in ATT
and flow territory is associated with the existence of high-grade ICA stenosis
(odds ratio = 12 and 21, respectively), whereas hemispherical asymmetry in CBF is
not. Our data suggest that ATT and flow territory may be better predictors of
asymptomatic high-grade ICA stenosis diagnosed by carotid ultrasonography than
CBF.
PMID- 28500301
TI - Characterization of prophages of Lactococcus garvieae.
AB - This report describes the morphological characterization and genome analysis of
an induced prophage (PLg-TB25) from a dairy strain of Lactococcus garvieae. The
phage belongs to the Siphoviridae family and its morphology is typical of other
lactococcal phages. A general analysis of its genome did not reveal similarities
with other lactococcal phage genomes, confirming its novelty. However,
similarities were found between genes of its morphogenesis cluster and genes of
Gram-positive bacteria, suggesting that this phage genome resulted from
recombination events that took place in a heterogeneous microbial environment. An
in silico search for other prophages in 16 L. garvieae genomes available in
public databases, uncovered eight seemingly complete prophages in strains
isolated from dairy and fish niches. Genome analyses of these prophages revealed
three novel L. garvieae phages. The remaining prophages had homology to phages of
Lactococcus lactis (P335 group) suggesting a close relationship between these
lactococcal species. The similarity in GC content of L. garvieae prophages to the
genomes of L. lactis phages further supports the hypothesis that these phages
likely originated from the same ancestor.
PMID- 28500303
TI - Photonic crystal and quasi-crystals providing simultaneous light coupling and
beam splitting within a low refractive-index slab waveguide.
AB - Coupling between free space components and slab waveguides is a common
requirement for integrated optical devices, and is typically achieved by end-fire
or grating coupling. Power splitting and distribution requires additional
components. Usually grating couplers are used in combination with MMI/Y-splitters
to do this task. In this paper, we present a photonic crystal device which
performs both tasks simultaneously and is able to couple light at normal
incidence and near normal incidence. Our approach is scalable to large channel
counts with little impact on device footprint. We demonstrate in normal incidence
coupling with multi-channel splitting for 785 nm light. Photonic crystals are
etched into single mode low refractive index SiON film on both SiO2/Si and
borosilicate glass substrate. Triangular lattices are shown to provide coupling
to 6 beams with equal included angle (60 degrees ), while a quasi-crystal lattice
with 12-fold rotational symmetry yields coupling to 12 beams with equal included
angle (30 degrees ). We show how to optimize the lattice constant to achieve
efficient phase matching between incident and coupled mode wave vectors, and how
to adjust operating wavelength from visible to infrared wavelengths.
PMID- 28500302
TI - Different Polyubiquitinated Bodies in Human Dendritic Cells: IL-4 Causes PaCS
During Differentiation while LPS or IFNalpha Induces DALIS During Maturation.
AB - Two types of polyubiquitin-reactive cytoplasmic bodies, particulate cytoplasmic
structures (PaCS) and dendritic cell (DC) aggresome-like induced structures
(DALIS), were analyzed by electron microscopy, immunocytochemistry,
immunoblotting, and flow cytometry in DC obtained from human blood monocytes
incubated with GM-CSF plus IL-4 (IL4-DC), GM-CSF plus IFNalpha (IFN-DC), or GM
CSF alone (GM-DC), with or without LPS maturation. PaCS developed as monomorphic
aggregates of proteasome-reactive barrel-like particles only in ribosomes-rich
cytoplasmic areas of differentiating IL4-DC. In contrast, DALIS formed as
vesicular bodies storing K63-linked ubiquitinated proteins by coalescence of
increased endosomal structures, in IFN-DC or after LPS maturation of GM-DC. DALIS
forming cells showed incomplete morphological and functional DC-type
differentiation when compared to PaCS-forming IL4-DC. PaCS and DALIS may have
different function as well as different origin and cytochemistry. DALIS may be a
transient accumulation site of potentially antigenic polyubiquitinated proteins
during their processing and presentation. PaCS are found under physiologic or
pathologic conditions associated with increased/deranged protein synthesis and
increased ubiquitin-proteasome activity. Given its high heat-shock protein
content PaCS may work as a quality control structure for newly synthesized,
cytosolic proteins. This comparative analysis suggests that PaCS and DALIS have
distinctive roles in DC.
PMID- 28500304
TI - Microgravity induces inhibition of osteoblastic differentiation and
mineralization through abrogating primary cilia.
AB - It is well documented that microgravity in space environment leads to bone loss
in astronauts. These physiological changes have also been validated by human and
animal studies and modeled in cell-based analogs. However, the underlying
mechanisms are elusive. In the current study, we identified a novel phenomenon
that primary cilia (key sensors and functioning organelles) of rat calvarial
osteoblasts (ROBs) gradually shrank and disappeared almost completely after
exposure to simulated microgravity generated by a random positioning machine
(RPM). Along with the abrogation of primary cilia, the differentiation,
maturation and mineralization of ROBs were inhibited. We also found that the
disappearance of primary cilia was prevented by treating ROBs with cytochalasin
D, but not with LiCl or dynein light chain Tctex-type 1 (Dynlt1) siRNA. The
repression of the differentiation, maturation and mineralization of ROBs was
effectively offset by cytochalasin D treatment in microgravity conditions.
Blocking ciliogenesis using intraflagellar transport protein 88 (IFT88) siRNA
knockdown inhibited the ability of cytochalasin D to counteract this reduction of
osteogenesis. These results indicate that the abrogation of primary cilia may be
responsible for the microgravity's inhibition on osteogenesis. Reconstruction of
primary cilia may become a potential strategy against bone loss induced by
microgravity.
PMID- 28500305
TI - NSAIDs Use and Reduced Metastasis in Cancer Patients: results from a meta
analysis.
AB - This meta-analysis investigated the relationship between non-steroidal anti
inflammatory drugs (NSAIDs) and lymph node/distant metastasis. Relevant sources
were identified from MEDLINE, EMBASE, PubMed, and Cochrane Library. Studies that
reported the odds ratio (OR)/risk ratio (RR)/hazard ratio (HR) with 95%
confidence intervals (CIs) for the associations of interested outcomes were
included. Pooled effect estimates were obtained by using random- or fixed-effect
model depending on the heterogeneity across these studies. Sixteen studies
involving 202780 participants, including prostate, breast, lung, and colorectal
cancer patients, were included. Compared with the reference, generally patients
exposed to NSAIDs at pre- and post-diagnosis experienced a significantly reduced
risk of distant metastasis (RR 0.708, 95% CI 0.586-0.856 and RR: 0.484, 95% CI:
0.393-0.595, respectively), including prostate cancer (pre-diagnostic use: RR =
0.874, 95% CI, 0.787-0.97; post-diagnostic use: RR = 0.482, 95% CI 0.359-0.647),
and breast cancer (pre-diagnostic use: RR = 0.644, 95% CI 0.565-0.735; post
diagnostic use: RR = 0.485, 95% CI 0.362-0.651). However, lymph node metastasis
was weakly related with pre-diagnostic use of NSAIDs (RR = 0.949, 95% CI 0.914
0.985). NSAIDs are related to a significantly reduced risk of metastasis
development, regardless of pre-diagnostic or post-diagnostic use. However, NSAIDs
and lymph node metastasis are weakly associated. Our finding suggested a novel
metastasis management.
PMID- 28500306
TI - Plasmonic Purcell effect reveals obliquely ordered phosphorescent emitters in
Organic LEDs.
AB - The non-isotropic alignment of molecules can increase the interaction efficiency
with propagating light fields. This applies to both emissive and absorptive
systems and can be exploited for achieving unprecedented efficiencies of organic
opto-electronic devices such as organic light-emitting diodes. Optical analysis
has revealed certain phosphorescent emitters to align spontaneously in an
advantageous orientation. Unfortunately, established approaches only determine an
average orientation because emission patterns solely depend on the second moments
of the transition dipole vector distribution. In order to resolve further details
of such a distribution, additional differences in the emission characteristics of
parallel and perpendicularly oriented emitters need to be introduced. A thin
metal layer near the emitters introduces plasmon mediated losses mostly for
perpendicular emitters. Then, analyzing the emission at different polarizations
allows one to measure emission lifetimes of mostly parallel or mostly
perpendicular oriented emitters. This should alter the transient emission when
observing the temporal phosphorescence decay under different directions and/or
polarizations. The angular width of the orientation distribution can be derived
from the degree of such lifetime splitting. Our results suggest a narrow but
obliquely oriented molecular ensemble of Ir(MDQ)2(acac) doped into the alpha-NPD
host inside an Organic LED stack.
PMID- 28500307
TI - ALOX5 exhibits anti-tumor and drug-sensitizing effects in MLL-rearranged
leukemia.
AB - MLL-rearranged acute myeloid leukemia (AML) remains a fatal disease with a high
rate of relapse and therapeutic failure due to chemotherapy resistance. In
analysis of our Affymetrix microarray profiling and chromatin immunoprecipitation
(ChIP) assays, we found that ALOX5 is especially down-regulated in MLL-rearranged
AML, via transcription repression mediated by Polycomb repressive complex 2
(PRC2). Colony forming/replating and bone marrow transplantation (BMT) assays
showed that Alox5 exhibited a moderate anti-tumor effect both in vitro and in
vivo. Strikingly, leukemic cells with Alox5 overexpression showed a significantly
higher sensitivity to the standard chemotherapeutic agents, i.e., doxorubicin
(DOX) and cytarabine (Ara-C). The drug-sensitizing role of Alox5 was further
confirmed in human and murine MLL-rearranged AML cell models in vitro, as well as
in the in vivo MLL-rearranged AML BMT model coupled with treatment of "5 + 3"
(i.e. DOX plus Ara-C) regimen. Stat and K-Ras signaling pathways were negatively
correlated with Alox5 overexpression in MLL-AF9-leukemic blast cells; inhibition
of the above signaling pathways mimicked the drug-sensitizing effect of ALOX5 in
AML cells. Collectively, our work shows that ALOX5 plays a moderate anti-tumor
role and functions as a drug sensitizer, with a therapeutic potential, in MLL
rearranged AML.
PMID- 28500308
TI - Ultrafast all-optical tuning of direct-gap semiconductor metasurfaces.
AB - Optical metasurfaces are regular quasi-planar nanopatterns that can apply diverse
spatial and spectral transformations to light waves. However, metasurfaces are no
longer adjustable after fabrication, and a critical challenge is to realise a
technique of tuning their optical properties that is both fast and efficient. We
experimentally realise an ultrafast tunable metasurface consisting of
subwavelength gallium arsenide nanoparticles supporting Mie-type resonances in
the near infrared. Using transient reflectance spectroscopy, we demonstrate a
picosecond-scale absolute reflectance modulation of up to 0.35 at the magnetic
dipole resonance of the metasurfaces and a spectral shift of the resonance by 30
nm, both achieved at unprecedentedly low pump fluences of less than 400 MUJ cm-2.
Our findings thereby enable a versatile tool for ultrafast and efficient control
of light using light.Metasurfaces are not adjustable after fabrication, and a
critical challenge is to realise a technique of tuning their optical properties
that is both fast and efficient. Here, Shcherbakov et al. realise an ultrafast
tunable metasurface with picosecond-scale large absolute reflectance modulation
at low pump fluences.
PMID- 28500309
TI - Resveratrol inhibits release of soluble fms-like tyrosine kinase (sFlt-1) and
soluble endoglin and improves vascular dysfunction - implications as a
preeclampsia treatment.
AB - Preeclampsia is a disease of pregnancy associated with placental oxidative
stress, inflammation and elevated release of anti-angiogenic factors sFlt-1 and
soluble endoglin. These placental factors cause generalized maternal endothelial
dysfunction. There are no treatments to halt disease progression; delivery is the
only cure. Resveratrol modulates pathways involved in inflammation and oxidative
stress and may offer a potential therapeutic for preeclampsia. Resveratrol
reduced sFlt-1, sFlt-1 e15a and soluble endoglin secretion from primary
trophoblasts and HUVECs and reduced mRNA expression of pro-inflammatory molecules
NFkappaB, IL-6 and IL-1beta in trophoblasts. IL-6, IL-1beta and TNFalpha
secretion were also significantly reduced. In HUVECs, resveratrol significantly
increased mRNA of anti-oxidant enzymes HO-1, NQO1, GCLC and TXN but did not
significantly alter HO-1 protein expression, whilst reducing HO-1 protein in
trophoblast. Endothelial dysfunction was induced in HUVECs using TNFalpha,
increasing expression of cell adhesion molecule VCAM1 and adhesion of peripheral
blood mononuclear cells, both of which were increased further by resveratrol. In
contrast, resveratrol significantly reduced TNFalpha-induced Endothelin-1 (a
vasoconstrictor) and significantly increased the phosphorylation of endothelial
nitric oxide synthase (eNOS). In summary, resveratrol decreases secretion of anti
angiogenic factors however its effects on the endothelium are mixed. Overall, it
may have potential as a treatment for preeclampsia.
PMID- 28500310
TI - Bio-Inspired nacre-like nanolignocellulose-poly (vinyl alcohol)-TiO2 composite
with superior mechanical and photocatalytic properties.
AB - Nacre, the gold standard for biomimicry, provides an excellent example and
guideline for assembling high-performance composites. Inspired by the layered
structure and extraordinary strength and toughness of natural nacre, nacre-like
nanolignocellulose/poly (vinyl alcohol)/TiO2 composites possessed the similar
layered structure of natural nacre were constructed through hot-pressing process.
Poly (vinyl alcohol) and TiO2 nanoparticles have been used as nanofillers to
improve the mechanical performance and synchronously endow the superior
photocatalytic activity of the composites. This research would be provided a
promising candidate for the photooxidation of volatile organic compounds also
combined with outstanding mechanical property.
PMID- 28500311
TI - Optimisation of a Novel Spiral-Inducing Bypass Graft Using Computational Fluid
Dynamics.
AB - Graft failure is currently a major concern for medical practitioners in treating
Peripheral Vascular Disease (PVD) and Coronary Artery Disease (CAD). It is now
widely accepted that unfavourable haemodynamic conditions play an essential role
in the formation and development of intimal hyperplasia, which is the main cause
of graft failure. This paper uses Computational Fluid Dynamics (CFD) to conduct a
parametric study to enhance the design and performance of a novel prosthetic
graft, which utilises internal ridge(s) to induce spiral flow. This design is
primarily based on the identification of the blood flow as spiral in the whole
arterial system and is believed to improve the graft longevity and patency rates
at distal graft anastomoses. Four different design parameters were assessed in
this work and the trailing edge orientation of the ridge was identified as the
most important parameter to induce physiological swirling flow, while the height
of the ridge also significantly contributed to the enhanced performance of this
type of graft. Building on these conclusions, an enhanced configuration of spiral
graft is proposed and compared against conventional and spiral grafts to reaffirm
its potential benefits.
PMID- 28500312
TI - Total tumour diameter is superior to unifocal diameter as a predictor of
papillary thyroid microcarcinoma prognosis.
AB - The current American Joint Committee (AJCC) on Cancer TNM classification does not
describe the treatment of multifocal papillary thyroid microcarcinomas (PTMCs)
with a total tumour diameter (TTD) >1 cm. Herein, we investigated this PTMC
subgroup in terms of extrathyroidal extension (ETE), local infiltration, central
lymph node metastasis (LNM), and prognosis. Consecutive patients (n = 1102) were
identified and the proportions of LNM, ETE, and local infiltration were similar
between PTCs with a unifocal tumour diameter >1 cm and <=2 cm and PTMCs with a
multifocal TTD >1 cm and <=2 cm. The proportions of LNM, ETE, and local
infiltration were also similar between PTMCs with a unifocal diameter <=1 cm vs.
multifocal TTD <=1 cm. However, when comparing PTMCs with a unifocal diameter <=1
cm vs. multifocal TTD >1 cm, significant differences were observed. In the Kaplan
Meier analysis, significant differences were observed between PTMCs with a
unifocal diameter <=1 cm vs. multifocal TTD >1 cm and multifocal TTD <=1 cm vs.
multifocal TTD >1 cm. Accordingly, TTD may represent a more accurate criterion
for tumour size of PTCs and should be considered in the revised AJCC staging
system.
PMID- 28500313
TI - The mitochondrial genomes of the acoelomorph worms Paratomella rubra, Isodiametra
pulchra and Archaphanostoma ylvae.
AB - Acoels are small, ubiquitous - but understudied - marine worms with a very simple
body plan. Their internal phylogeny is still not fully resolved, and the position
of their proposed phylum Xenacoelomorpha remains debated. Here we describe
mitochondrial genome sequences from the acoels Paratomella rubra and Isodiametra
pulchra, and the complete mitochondrial genome of the acoel Archaphanostoma
ylvae. The P. rubra and A. ylvae sequences are typical for metazoans in size and
gene content. The larger I. pulchra mitochondrial genome contains both ribosomal
genes, 21 tRNAs, but only 11 protein-coding genes. We find evidence suggesting a
duplicated sequence in the I. pulchra mitochondrial genome. The P. rubra, I.
pulchra and A. ylvae mitochondria have a unique genome organisation in comparison
to other metazoan mitochondrial genomes. We found a large degree of protein
coding gene and tRNA overlap with little non-coding sequence in the compact P.
rubra genome. Conversely, the A. ylvae and I. pulchra genomes have many long non
coding sequences between genes, likely driving genome size expansion in the
latter. Phylogenetic trees inferred from mitochondrial genes retrieve
Xenacoelomorpha as an early branching taxon in the deuterostomes. Sequence
divergence analysis between P. rubra sampled in England and Spain indicates
cryptic diversity.
PMID- 28500314
TI - Activation of Eosinophils Interacting with Bronchial Epithelial Cells by
Antimicrobial Peptide LL-37: Implications in Allergic Asthma.
AB - The role of antimicrobial peptide LL-37 in asthma exacerbation is unclear.
Microbial infection, which is the most common inducer of asthma exacerbation, is
accompanied by elevated LL-37. The present study found that co-culture of
eosinophils and bronchial epithelial cell line BEAS-2B significantly enhanced
intercellular adhesion molecule-1 on both cells and CD18 expression on
eosinophils upon LL-37 stimulation. IL-6, CXCL8 and CCL4 were substantially
released in co-culture in the presence of LL-37. LL-37 triggered the activation
of eosinophils interacting with BEAS-2B cells in a P2X purinoceptor 7/epidermal
growth factor receptor-dependent manner. Eosinophils and BEAS-2B cells
differentially contribute to the expression of cytokines/chemokines in co
culture, while soluble mediators were sufficient to mediate the intercellular
interactions. Intracellular p38-mitogen-activated protein kinase, extracellular
signal-regulated kinase and NF-kappaB signaling pathways were essential for LL-37
mediated activation of eosinophils and BEAS-2B cells. By using the ovalbumin
induced asthmatic model, intranasal administration of mCRAMP (mouse ortholog of
LL-37) in combination with ovalbumin during the allergen challenge stage
significantly enhanced airway hyperresponsiveness and airway inflammation in
sensitized mice, thereby implicating a deteriorating role of LL-37 in allergic
asthma. This study provides evidence of LL-37 in triggering asthma exacerbation
via the activation of eosinophils interacting with bronchial epithelial cells in
inflammatory airway.
PMID- 28500315
TI - Network and role analysis of autophagy in Phytophthora sojae.
AB - Autophagy is an evolutionarily conserved mechanism in eukaryotes with roles in
development and the virulence of plant fungal pathogens. However, few reports on
autophagy in oomycete species have been published. Here, we identified 26
autophagy-related genes (ATGs) belonging to 20 different groups in Phytophthora
sojae using a genome-wide survey, and core ATGs in oomycetes were used to
construct a preliminary autophagy pathway model. Expression profile analysis
revealed that these ATGs are broadly expressed and that the majority of them
significantly increase during infection stages, suggesting a central role for
autophagy in virulence. Autophagy in P. sojae was detected using a GFP-PsAtg8
fusion protein and the fluorescent dye MDC during rapamycin and starvation
treatment. In addition, autophagy was significantly induced during sporangium
formation and cyst germination. Silencing PsAtg6a in P. sojae significantly
reduced sporulation and pathogenicity. Furthermore, a PsAtg6a-silenced strain
showed haustorial formation defects. These results suggested that autophagy might
play essential roles in both the development and infection mechanism of P. sojae.
PMID- 28500316
TI - Establishment of a Strong Link Between Smoking and Cancer Pathogenesis through
DNA Methylation Analysis.
AB - Smoking is a well-documented risk factor in various cancers, especially lung
cancer. In the current study, we tested the hypothesis that abnormal DNAm loci
associated with smoking are enriched in genes and pathways that convey a risk of
cancer by determining whether smoking-related methylated genes led to enrichment
in cancer-related pathways. We analyzed two sets of smoking-related methylated
genes from 28 studies originating from blood and buccal samples. By analyzing 320
methylated genes from 26 studies on blood samples (N = 17,675), we found 57
enriched pathways associated with different types of cancer (FDR < 0.05). Of
these, 11 were also significantly overrepresented in the 661 methylated genes
from two studies of buccal samples (N = 1,002). We further found the aryl
hydrocarbon receptor signaling pathway plays an important role in the initiation
of smoking-attributable cancer. Finally, we constructed a subnetwork of genes
important for smoking-attributable cancer from the 48 non-redundant genes in the
11 oncogenic pathways. Of these, genes such as DUSP4 and AKT3 are well documented
as being involved in smoking-related lung cancer. In summary, our findings
provide robust and systematic evidence in support of smoking's impact on the
epigenome, which may be an important contributor to cancer.
PMID- 28500317
TI - Optical properties of monolayer tinene in electric fields.
AB - The absorption spectra of monolayer tinene in perpendicular electric fields are
studied by the tight-binding model. There are three kinds of special structures,
namely shoulders, logarithmical symmetric peaks and asymmetric peaks in the
square-root form, corresponding to the optical excitations of the extreme points,
saddle points and constant-energy loops. With the increasing field strength, two
splitting shoulder structures, which are dominated by the parabolic bands of 5p z
orbitals, come to exist because of the spin-split energy bands. The frequency of
threshold shoulder declines to zero and then linearly grows. The third shoulder
at 0.75~0.85 eV mainly comes from (5p x , 5p y ) orbitals. The former and the
latter orbitals, respectively, create the saddle-point symmetric peaks near the M
point, while they hybridize with one another to generate the loop-related
asymmetric peaks. Tinene quite differs from graphene, silicene, and germanene.
The special relationship among the multi-orbital chemical bondings, spin-orbital
couplings and Coulomb potentials accounts for the feature-rich optical
properties.
PMID- 28500318
TI - Direct Observation of Sink-Dependent Defect Evolution in Nanocrystalline Iron
under Irradiation.
AB - Crystal defects generated during irradiation can result in severe changes in
morphology and an overall degradation of mechanical properties in a given
material. Nanomaterials have been proposed as radiation damage tolerant
materials, due to the hypothesis that defect density decreases with grain size
refinement due to the increase in grain boundary surface area. The lower defect
density should arise from grain boundary-point defect absorption and enhancement
of interstitial-vacancy annihilation. In this study, low energy helium ion
irradiation on free-standing iron thin films were performed at 573 K.
Interstitial loops of a 0 /2 [111] Burgers vector were directly observed as a
result of the displacement damage. Loop density trends with grain size
demonstrated an increase in the nanocrystalline (<100 nm) regime, but scattered
behavior in the transition from the nanocrystalline to the ultra-fine regime (100
500 nm). To examine the validity of such trends, loop density and area for
different grains at various irradiation doses were compared and revealed
efficient defect absorption in the nanocrystalline grain size regime, but loop
coalescence in the ultra-fine grain size regime. A relationship between the
denuded zone formation, a measure of grain boundary absorption efficiency, grain
size, grain boundary type and misorientation angle is determined.
PMID- 28500320
TI - Oral administration of trace element magnesium significantly improving the
cognition and locomotion in hepatic encephalopathy rats.
AB - The therapeutic effects of iron, zinc and magnesium trace elements, as well as
rifaximin were investigated and compared in HE rats. In this study, HE rats were
treated with either ferrous sulfate (HE-Fe, 30 mg/kg/day), zinc sulfate (HE-Zn,
30 mg/kg/day), magnesium sulfate (HE-Mg, 50 mg/kg/day) or rifaximin (HE-Rf, 50
mg/kg/day), which was mixed with water and administered orally for 61 days. The
Morris water maze (MWM) and open-field tests were used to evaluate cognitive and
locomotor function. The blood ammonia levels before and after administration of
the glutamine challenge test, manganese concentration and glutamine synthetase
(GS) activity were measured. Significantly longer MWM escape latencies, less
locomotor activity, higher blood ammonia levels, higher brain manganese
concentrations and higher GS activity were observed in HE rats. However, HE-Mg
and HE-Rf rats had significantly shorter MWM escape latencies, increased
locomotor activity, lower blood ammonia, lower brain manganese concentrations and
lower GS activity. Partial improvements were observed in HE-Fe and HE-Zn rats.
The results indicated that oral administration of magnesium can significantly
improve the cognitive and locomotor functions in HE rats by reducing the brain
manganese concentration and regulating GS activity.
PMID- 28500319
TI - Airway Microbial Diversity is Inversely Associated with Mite-Sensitized Rhinitis
and Asthma in Early Childhood.
AB - Microbiota plays an important role in regulating immune responses associated with
atopic diseases. We sought to evaluate relationships among airway microbiota,
serum IgE levels, allergic sensitization and their relevance to rhinitis and
asthma. Microbial characterization was performed using Illumina-based 16S rRNA
gene sequencing of 87 throat swabs collected from children with asthma (n = 32)
and rhinitis (n = 23), and from healthy controls (n = 32). Data analysis was
performed using QIIME (Quantitative Insights Into Microbial Ecology) v1.8.
Significantly higher abundance of Proteobacteria was found in children with
rhinitis than in the healthy controls (20.1% vs. 16.1%, P = 0.009). Bacterial
species richness (Chao1 index) and diversity (Shannon index) were significantly
reduced in children with mite sensitization but not in those with food or IgE
sensitization. Compared with healthy children without mite sensitization, the
mite-sensitized children with rhinitis and asthma showed significantly lower
Chao1 and Shannon indices. Moraxella and Leptotrichia species were significantly
found in the interaction of mite sensitization with rhinitis and asthma
respectively. Airway microbial diversity appears to be inversely associated with
sensitization to house dust mites. A modulation between airway dysbiosis and
responses to allergens may potentially cause susceptibility to rhinitis and
asthma in early childhood.
PMID- 28500321
TI - Twinning-induced plasticity (TWIP) and work hardening in Ti-based metallic glass
matrix composites.
AB - The present study demonstrates that Ti-based metallic glass matrix composites
(MGMCs) with a normal composition of Ti43Zr32Ni6Ta5Be14 containing ductile
dendrites dispersed in the glass matrix has been developed, and deformation
mechanisms about the tensile property have been investigated by focusing on
twinning-induced plasticity (TWIP) effect. The Ti-based MGMC has excellent
tensile properties and pronounced tensile work-hardening capacity, with a yield
strength of 1100 MPa and homogeneous elongation of 4%. The distinguished strain
hardening is ascribed to the formation of deformation twinning within the
dendrites. Twinning generated in the dendrites works as an obstacle for the rapid
propagation of shear bands, and then, the localized necking is avoided, which
ensures the ductility of such kinds of composites. Besides, a finite-element
model (FEM) has been established to explain the TWIP effect which brings out a
work-hardening behavior in the present MGMC instead of a localized strain
concentration. According to the plasticity theory of traditional crystal
materials and some new alloys, TWIP effect is mainly controlled by stacking fault
energy (SFE), which has been analyzed intensively in the present MGMC.
PMID- 28500322
TI - Incidence and predictors of HBV relapse after cessation of nucleoside analogues
in HBeAg-negative patients with HBsAg <= 200 IU/mL.
AB - The predictors of hepatitis B virus (HBV) relapse and HBsAg loss after cessation
of nucleos(t)ide analogues (NA) in HBeAg-negative patients with end-of-treatment
HBsAg <= 200 IU/mL remains unclear. The study recruited 119 chronic hepatitis B
(CHB) patients who achieved end-of-treatment HBsAg <= 200 IU/mL, were treated
with lamivudine (n = 34) and entecavir (n = 85). The 5-year rates of post
treatment virological relapse, clinical relapse, and HBsAg loss at 60 months were
39.4%, 27.6%, and 45.9%, respectively. Cox regression analysis revealed that HBV
DNA at entry and end-of-treatment HBsAg levels were independent predictors of
virolgical and clinical relapse. HBV genotype C and end-of-treatment HBsAg were
independent factors of HBsAg loss. Patients with a combination of end-of
treatment HBsAg < 50 IU/mL and HBV DNA < 2 * 105 IU/mL at entry experienced the
lowest virological and clinical relapse rates (5% and 0% at 60 months,
respectively). In contract, patients with a combination of end-of-treatment HBsAg
>= 50 IU/mL and HBV DNA >= 2 * 105 IU/mL at entry experienced high virological
and clinical relapse (80.7% and 71.5% at 60 months, respectively). No patients
experienced hepatic decompensation when clinical relapse occurred after timely
retreatment. A combination of HBV DNA levels at entry and end-of-treatment HBsAg
levels was useful for predicting the post-treatment HBV relapse in HBeAg-negative
patients with HBsAg <= 200 IU/mL.
PMID- 28500323
TI - Development of an inducible mouse model of iRFP713 to track recombinase activity
and tumour development in vivo.
AB - While the use of bioluminescent proteins for molecular imaging is a powerful
technology to further our understanding of complex processes, fluorescent
labeling with visible light fluorescent proteins such as GFP and RFP suffers from
poor tissue penetration and high background autofluorescence. To overcome these
limitations, we generated an inducible knock-in mouse model of iRFP713. This
model was used to assess Cre activity in a Rosa Cre-ER background and quantify
Cre activity upon different tamoxifen treatments in several organs. We also show
that iRFP can be readily detected in 3D organoid cultures, FACS analysis and in
vivo tumour models. Taken together we demonstrate that iRFP713 is a progressive
step in in vivo imaging and analysis that widens the optical imaging window to
the near-infrared spectrum, thereby allowing deeper tissue penetration, quicker
image acquisition without the need to inject substrates and a better signal to
background ratio in genetically engineered mouse models (GEMMs).
PMID- 28500324
TI - Labeling Extracellular Vesicles for Nanoscale Flow Cytometry.
AB - Extracellular vesicles (EVs), including exosomes and microvesicles, are 30-800 nm
vesicles that are released by most cell types, as biological packages for
intercellular communication. Their importance in cancer and inflammation makes
EVs and their cargo promising biomarkers of disease and cell-free therapeutic
agents. Emerging high-resolution cytometric methods have created a pressing need
for efficient fluorescent labeling procedures to visualize and detect EVs.
Suitable labels must be bright enough for one EV to be detected without the
generation of label-associated artifacts. To identify a strategy that robustly
labels individual EVs, we used nanoFACS, a high-resolution flow cytometric method
that utilizes light scattering and fluorescence parameters along with sample
enumeration, to evaluate various labels. Specifically, we compared lipid-,
protein-, and RNA-based staining methods and developed a robust EV staining
strategy, with the amine-reactive fluorescent label, 5-(and-6)-Carboxyfluorescein
Diacetate Succinimidyl Ester, and size exclusion chromatography to remove
unconjugated label. By combining nanoFACS measurements of light scattering and
fluorescence, we evaluated the sensitivity and specificity of EV labeling assays
in a manner that has not been described for other EV detection methods. Efficient
characterization of EVs by nanoFACS paves the way towards further study of EVs
and their roles in health and disease.
PMID- 28500325
TI - Catechol-Functional Chitosan/Silver Nanoparticle Composite as a Highly Effective
Antibacterial Agent with Species-Specific Mechanisms.
AB - In this study, silver nanoparticles (Ag NPs) coated with catechol-conjugated
chitosan (CSS) were prepared using green methods. Interestingly, we uncovered
that CSS-coated Ag NPs (CSS-Ag NPs) exhibited a higher toxicity against gram
negative Escherichia coli (E. coli) bacteria than against gram-positive
Staphylococcus aureus (S. aureus) bacteria. The differences revealed that the CSS
Ag NPs killed gram bacteria with distinct, species-specific mechanisms. The aim
of this study is to further investigate these underlying mechanisms through a
series of analyses. The ultrastructure and morphology of the bacteria before and
after treatment with CSS-Ag NPs were observed. The results demonstrated the CSS
Ag NPs killed gram-positive bacteria through a disorganization of the cell wall
and leakage of cytoplasmic content. In contrast, the primary mechanism of action
on gram-negative bacteria was a change in membrane permeability, induced by
adsorption of CSS-Ag NPs. The species-specific mechanisms are caused by
structural differences in the cell walls of gram bacteria. Gram-positive bacteria
are protected from CSS-Ag NPs by a thicker cell wall, while gram-negatives are
more easily killed due to an interaction between a special outer membrane and the
nanoparticles. Our study offers an in-depth understanding of the antibacterial
behaviors of CSS-Ag NPs and provides insights into ultimately optimizing the
design of Ag NPs for treatment of bacterial infections.
PMID- 28500327
TI - Metazoan Ribosome Inactivating Protein encoding genes acquired by Horizontal Gene
Transfer.
AB - Ribosome inactivating proteins (RIPs) are RNA N-glycosidases that depurinate a
specific adenine residue in the conserved sarcin/ricin loop of 28S rRNA. These
enzymes are widely distributed among plants and their presence has also been
confirmed in several bacterial species. Recently, we reported for the first time
in silico evidence of RIP encoding genes in metazoans, in two closely related
species of insects: Aedes aegypti and Culex quinquefasciatus. Here, we have
experimentally confirmed the presence of these genes in mosquitoes and attempted
to unveil their evolutionary history. A detailed study was conducted, including
evaluation of taxonomic distribution, phylogenetic inferences and microsynteny
analyses, indicating that mosquito RIP genes derived from a single Horizontal
Gene Transfer (HGT) event, probably from a cyanobacterial donor species.
Moreover, evolutionary analyses show that, after the HGT event, these genes
evolved under purifying selection, strongly suggesting they play functional roles
in these organisms.
PMID- 28500326
TI - Intranasal drug delivery of small interfering RNA targeting Beclin1 encapsulated
with polyethylenimine (PEI) in mouse brain to achieve HIV attenuation.
AB - We previously reported that activation of the host autophagic protein, Beclin1,
by HIV-1 infection represents an essential mechanism in controlling HIV
replication and viral-induced inflammatory responses in microglial cells.
Existing antiretroviral therapeutic approaches have been limited in their ability
to cross the blood-brain barrier effectively and recognize and selectively
eliminate persistent HIV-infected brain reservoirs. In the present study and for
the first time, the bio-distribution and efficacy of noninvasive intranasal
delivery of small interfering RNA (siRNA) against the Beclin1 gene using the
cationic linear polyethylenimines (PEI) as a gene carrier was investigated in
adult mouse brain. Fluorescein isothiocyanate (FITC)-labeled control siRNA
delivered intranasally was found in the cytoplasm of neurons and glial cells of
the prefrontal cortex at 4 and 24 hours post-delivery, with no major adverse
immune reaction encountered. Intranasal delivery of the siRNA targeting Beclin1
significantly depleted the target protein expression levels in brain tissues with
no evidence of toxicity. Binding of siRNA to PEI-polymer was characterized and
confirmed by Raman spectroscopy. These results indicate that the intranasal drug
delivery allows for the direct delivery of the PEI-siRNA nano-complex to the
central nervous system, which could potentially offer an efficient means of gene
silencing-mediated therapy in the HIV-infected brain.
PMID- 28500328
TI - Spatial topologies affect local food web structure and diversity in evolutionary
metacommunities.
AB - An important challenge in theoretical ecology is to better predict ecological
responses to environmental change, and in particular to spatial changes such as
habitat fragmentation. Classical food-web models have focused on purely
ecological predictions, without taking adaptation or evolution of species traits
into account. We address this issue using an eco-evolutionary model, which is
based on body masses and diets as the key traits that determine metabolic rates
and trophic interactions. The model implements evolution by the introduction of
new morphs that are related to the existing ones, so that the network structure
itself evolves in a self-organized manner. We consider the coupling and
decoupling of habitats in multi-trophic metacommunities consisting of 2 or 4
habitats. Our model thus integrates metacommunity models, which describe
ecosystems as networks of networks, with large community evolution models. We
find that rescue effects and source-sink effects occur within coupled habitats,
which have the potential to change local selection pressures so that the local
food web structure shows a fingerprint of its spatial conditions. Within our
model system, we observe that habitat coupling increases the lifetimes of top
predators and promotes local biodiversity.
PMID- 28500329
TI - No evidence of inbreeding depression in a Tasmanian devil insurance population
despite significant variation in inbreeding.
AB - Inbreeding depression occurs when inbred individuals experience reduced fitness
as a result of reduced genome-wide heterozygosity. The Tasmanian devil faces
extinction due to a contagious cancer, devil facial tumour disease (DFTD). An
insurance metapopulation was established in 2006 to ensure the survival of the
species and to be used as a source population for re-wilding and genetic rescue.
The emergence of DFTD and the rapid decline of wild devil populations have
rendered the species at risk of inbreeding depression. We used 33 microsatellite
loci to (1) reconstruct a pedigree for the insurance population and (2) estimate
genome-wide heterozygosity for 200 individuals. Using heterozygosity-fitness
correlations, we investigated the effect of heterozygosity on six diverse fitness
measures (ulna length, asymmetry, weight-at-weaning, testes volume, reproductive
success and survival). Despite statistically significant evidence of variation in
individual inbreeding in this population, we found no associations between
inbreeding and any of our six fitness measurements. We propose that the benign
environment in captivity may decrease the intensity of inbreeding depression,
relative to the stressful conditions in the wild. Future work will need to
measure fitness of released animals to facilitate translation of this data to the
broader conservation management of the species in its native range.
PMID- 28500330
TI - Genotyping-by-sequencing of three mapping populations for identification of
candidate genomic regions for resistance to sterility mosaic disease in
pigeonpea.
AB - Sterility mosaic disease (SMD) is one of the serious production constraints that
may lead to complete yield loss in pigeonpea. Three mapping populations including
two recombinant inbred lines and one F2, were used for phenotyping for SMD
resistance at two locations in three different years. Genotyping-by-sequencing
approach was used for simultaneous identification and genotyping of SNPs on above
mentioned populations. In total, 212,464, 89,699 and 64,798 SNPs were identified
in ICPL 20096 * ICPL 332 (PRIL_B), ICPL 20097 * ICP 8863 (PRIL_C) and ICP 8863 *
ICPL 87119 (F2) respectively. By using high-quality SNPs, genetic maps were
developed for PRIL_B (1,101 SNPs; 921.21 cM), PRIL_C (484 SNPs; 798.25 cM) and F2
(996 SNPs; 1,597.30 cM) populations. The average inter marker distance on these
maps varied from 0.84 cM to 1.65 cM, which was lowest in all genetic mapping
studies in pigeonpea. Composite interval mapping based QTL analysis identified a
total of 10 QTLs including three major QTLs across the three populations. The
phenotypic variance of the identified QTLs ranged from 3.6 to 34.3%. One
candidate genomic region identified on CcLG11 seems to be promising QTL for
molecular breeding in developing superior lines with enhanced resistance to SMD.
PMID- 28500331
TI - Transcriptome sequencing and phylogenetic analysis of four species of luminescent
beetles.
AB - The evolution of bioluminescence has prompted scientific attention to illuminate
phylogenetic relationships of luminescent beetles. However, genomic resources are
virtually lacking in rhagophthalmids (Rhagophthalmidae) and their related firefly
beetles lampyrids (Lampyridae). Here, we employed the Illumina Hiseq 2000
platform and sequenced the whole-body transcriptomes of the four luminescent
beetles: one rhagophthalmid (Rhagophthalmus sp.) and three fireflies
(Asymmetricata circumdata, Aquatica ficta, and Pyrocoelia pectoralis). We
obtained 55.4, 43.4, 38.6, and 36.7 million clean reads for the four species,
respectively. All reads were assembled into contigs from which unigenes were
derived. All unigenes were annotated by publicly available databases, and a total
of 4325 orthologous genes were identified. Using multiple phylogenetic
approaches, our transcriptome data confirmed the distinctiveness of
Rhagophthalmidae from Lampyridae, which was also supported by our mitogenome
analysis using three newly determined mitogenome sequences and 12 previously
published ones. Together, this study is the first report of whole transcriptome
sequencing data in Rhagophthalmidae and Lampyridae species, representing a
valuable genomic resource for studying the origin and evolution of some
remarkable traits in these beetles such as bioluminescence. Moreover, our
transcriptome and mitogenome data provide useful phylogenetic information that
could be of importance in future studies of phylogenetic inference.
PMID- 28500333
TI - Novel Algorithms for Improved Sensitivity in Non-Invasive Prenatal Testing.
AB - Non-invasive prenatal testing (NIPT) of cell-free DNA in maternal plasma, which
is a mixture of maternal DNA and a low percentage of fetal DNA, can detect fetal
aneuploidies using massively parallel sequencing. Because of the low percentage
of fetal DNA, methods with high sensitivity and precision are required. However,
sequencing variation lowers sensitivity and hampers detection of trisomy samples.
Therefore, we have developed three algorithms to improve sensitivity and
specificity: the chi-squared-based variation reduction (chi2VR), the regression
based Z-score (RBZ) and the Match QC score. The chi2VR reduces variability in
sequence read counts per chromosome between samples, the RBZ allows for more
precise trisomy prediction, and the Match QC score shows if the control group
used is representative for a specific sample. We compared the performance of
chi2VR to that of existing variation reduction algorithms (peak and GC
correction) and that of RBZ to trisomy prediction algorithms (standard Z-score,
normalized chromosome value and median-absolute-deviation-based Z-score). chi2VR
and the RBZ both reduce variability more than existing methods, and thereby
increase the sensitivity of the NIPT analysis. We found the optimal combination
of algorithms was to use both GC correction and chi2VR for pre-processing and to
use RBZ as the trisomy prediction method.
PMID- 28500334
TI - Using change trajectories to study the impacts of multi-annual habitat loss on
fledgling production in an old forest specialist bird.
AB - The loss and subdivision of habitat into smaller and more spatially isolated
units due to human actions has been shown to adversely affect species worldwide.
We examined how changes in old forest cover during eight years were associated
with the cumulative number of fledged offspring at the end of study period in
Eurasian treecreepers (Certhia familiaris) in Central Finland. We were
specifically interested in whether the initial level of old forest cover
moderated this relation. We applied a flexible and powerful approach, latent
growth curve modelling in a structural equation modeling (SEM) framework, to
create trajectories describing changes in old forest cover through time, and
studied how this change at both the territory core and landscape scales impacted
fledging numbers. Our main finding was that at the territory core scale the
negative impact of habitat loss on fledging numbers was lessened by the higher
levels of initial forest cover, while no association was found at the landscape
scale. Our study highlights a powerful, but currently under-utilised methodology
among ecologists that can provide important information about biological
responses to changes in the environment, providing a mechanistic way to study how
land cover dynamics can affect species responses.
PMID- 28500332
TI - Sexual homomorphism in dioecious trees: extensive tests fail to detect sexual
dimorphism in Populus ?.
AB - The evolution of sexual dimorphism and expansion of sex chromosomes are both
driven through sexual conflict, arising from differing fitness optima between
males and females. Here, we pair work in poplar (Populus) describing one of the
smallest sex-determining regions known thus far in complex eukaryotes (~100 kbp)
with comprehensive tests for sexual dimorphism using >1300 individuals from two
Populus species and assessing 96 non-reproductive functional traits. Against
expectation, we found sexual homomorphism (no non-reproductive trait differences
between the sexes), suggesting that gender is functionally neutral with respect
to non-reproductive features that affect plant survival and fitness. Combined
with a small sex-determining region, we infer that sexual conflict may be
effectively stymied or non-existent within these taxa. Both sexual homomorphism
and the small sex-determining region occur against a background of strong
environmental selection and local adaptation in Populus. This presents a powerful
hypothesis for the evolution of dioecious species. Here, we suggest that
environmental selection may be sufficient to suppress and stymy sexual conflict
if it acts orthogonal to sexual selection, thereby placing limitations on the
evolution of sexual dimorphism and genomic expansion of sex chromosomes.
PMID- 28500335
TI - Nutrient consumption and chain tuning in diatoms exposed to storm-like
turbulence.
AB - Current information on the response of phytoplankton to turbulence is linked to
cell size and nutrient availability. Diatoms are considered to be favored by
mixing as dissolved nutrients are more easily accessible for non-motile cells. We
investigated how diatoms exploit microscale turbulence under nutrient repletion
and depletion conditions. Here, we show that the chain-forming diatom Chaetoceros
decipiens, continues to take up phosphorus and carbon even when silicon is
depleted during turbulence. Our findings indicate that upon silica depletion,
during turbulence, chain spectra of C. decipiens remained unchanged. We show here
that longer chains are maintained during turbulence upon silica depletion whereas
under still conditions, shorter chains are enriched. We interpret this as a sign
of good physiological state leading to a delay of culture senescence. Our results
show that C. decipiens senses and responds to turbulence both in nutrient
repletion and depletion. This response is noteworthy due to the small size of the
species. The coupling between turbulence and biological response that we depict
here may have significant ecological implications. Considering the predicted
increase of storms in Northern latitudes this response might modify community
structure and succession. Our results partly corroborate Margalef's mandala and
provide additional explanations for that conceptualization.
PMID- 28500336
TI - Phylogeographical structure and demographic expansion in the endemic alpine
stream salamander (Hynobiidae: Batrachuperus) of the Qinling Mountains.
AB - The Qinling Mountains of China provide an excellent study area for assessing the
effect of Pleistocene climatic oscillations and paleogeological events on
intraspecific diversification. To assess genetic diversity of an endemic stream
salamander, Batrachuperus tibetanus, for its conservation, a phylogeographical
survey was performed based on mitochondrial DNA and morphological data. The
mitochondrial data revealed three lineages of B. tibetanus in the Qinling
Mountains. A lineage present in the northwestern Qinling Mountains groups with
the Tibet lineage of B. tibetanus, and the remaining Qinling populations are
eastern and western lineages that separated ~3-4 million years ago (Ma). The
eastern and western Qinling lineage delineation is supported by three
morphological variables (snout length, eye diameter and axilla-groin length). The
divergence of the two major lineages was likely caused by orogenesis of the
Qinling Mountains during the late Cenozoic, and the two lineages were
subsequently affected at different levels by Pleistocene climatic oscillations
showing different signals of demographic expansion. A large suitable area of B.
tibetanus through the Qinling Mountains since the last glacial maximum (LGM)
indicated the adaptation of this species to the climatic changes. However, low
genetic diversity within populations indicate the urgency of preserving the
vulnerable populations and endemic lineages.
PMID- 28500337
TI - Examining the efficacy of intravenous administration of predatory bacteria in
rats.
AB - The proteobacteria Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus are
obligate predators of Gram-negative bacteria, and have been proposed to be used
to treat multidrug-resistant bacterial infections. The ability of predatory
bacteria to reduce bacterial burden in vivo within the lungs of rats has been
demonstrated, but it was unknown if predatory bacteria can attenuate systemic
bacterial burden administered intravenously. In this study, we first assessed the
safety of intravenous inoculation of predatory bacteria in rats. No rat morbidity
or adverse histopathology of various organs due to predatory bacteria
administration was observed. An increase in proinflammatory cytokines (TNFalpha
and KC/GRO) was observed at two hours post-inoculation; however, cytokines
returned to baseline levels by 18 hours. Furthermore, bacterial dissemination
analysis demonstrated that predatory bacteria were efficiently cleared from the
host by 20 days post-injection. To determine whether predatory bacteria could
reduce bacterial burden in vivo, Klebsiella pneumoniae was injected into the tail
veins of rats and followed with multiple doses of predatory bacteria over 16 or
24 hours. Predatory bacteria were unable to significantly reduce K. pneumoniae
burden in the blood or prevent dissemination to other organs. The results suggest
that predatory bacteria may not be effective for treatment of acute blood
infections.
PMID- 28500338
TI - Inflammatory bacteriome featuring Fusobacterium nucleatum and Pseudomonas
aeruginosa identified in association with oral squamous cell carcinoma.
AB - Studies on the possible association between bacteria and oral squamous cell
carcinoma (OSCC) remain inconclusive, largely due to methodological
variations/limitations. The objective of this study was to characterize the
species composition as well as functional potential of the bacteriome associated
with OSCC. DNA obtained from 20 fresh OSCC biopsies (cases) and 20 deep
epithelium swabs (matched control subjects) was sequenced for the V1-V3 region
using Illumina's 2 * 300 bp chemistry. High quality, non-chimeric merged reads
were classified to species level using a prioritized BLASTN-algorithm. Downstream
analyses were performed using QIIME, PICRUSt, and LEfSe. Fusobacterium nucleatum
subsp. polymorphum was the most significantly overrepresented species in the
tumors followed by Pseudomonas aeruginosa and Campylobacter sp. Oral taxon 44,
while Streptococcus mitis, Rothia mucilaginosa and Haemophilus parainfluenzae
were the most significantly abundant in the controls. Functional prediction
showed that genes involved in bacterial mobility, flagellar assembly, bacterial
chemotaxis and LPS synthesis were enriched in the tumors while those responsible
for DNA repair and combination, purine metabolism, phenylalanine, tyrosine and
tryptophan biosynthesis, ribosome biogenesis and glycolysis/gluconeogenesis were
significantly associated with the controls. This is the first epidemiological
evidence for association of F. nucleatum and P. aeruginosa with OSCC.
Functionally, an "inflammatory bacteriome" is enriched in OSSC.
PMID- 28500339
TI - A role for core planar polarity proteins in cell contact-mediated orientation of
planar cell division across the mammalian embryonic skin.
AB - The question of how cell division orientation is determined is fundamentally
important for understanding tissue and organ shape in both healthy or disease
conditions. Here we provide evidence for cell contact-dependent orientation of
planar cell division in the mammalian embryonic skin. We propose a model where
the core planar polarity proteins Celsr1 and Frizzled-6 (Fz6) communicate the
long axis orientation of interphase basal cells to neighbouring basal mitoses so
that they align their horizontal division plane along the same axis. The
underlying mechanism requires a direct, cell surface, planar polarised cue, which
we posit depends upon variant post-translational forms of Celsr1 protein coupled
to Fz6. Our hypothesis has parallels with contact-mediated division orientation
in early C. elegans embryos suggesting functional conservation between the
adhesion-GPCRs Celsr1 and Latrophilin-1. We propose that linking planar cell
division plane with interphase neighbour long axis geometry reinforces axial bias
in skin spreading around the mouse embryo body.
PMID- 28500340
TI - Both haemagglutinin-specific antibody and T cell responses induced by a
chimpanzee adenoviral vaccine confer protection against influenza H7N9 viral
challenge.
AB - Since 2013, the outbreak or sporadic infection of a new reassortant H7N9
influenza virus in China has resulted in hundreds of deaths and thousands of
illnesses. An H7N9 vaccine is urgently needed, as a licensed human vaccine
against H7N9 influenza is currently not available. Here, we developed a
recombinant adenovirus-based vaccine, AdC68-H7HA, by cloning the H7N9
haemagglutinin (HA) gene into the chimpanzee adenoviral vector AdC68. The
efficacy of AdC68-H7HA was evaluated in mice as well as guinea pigs. For
comparison, an H7N9 DNA vaccine based on HA was also generated and tested in mice
and guinea pigs. The results demonstrated that both AdC68-H7HA and the DNA
vaccine prime-adenovirus boost regimen induced potent immune responses in animals
and completely protected mice from lethal H7N9 influenza viral challenge. A post
immunization serum transfer experiment showed that antibody responses could
completely protect against lethal challenge, while a T cell depletion experiment
indicated that HA-specific CD8+ T cells responses also contributed to protection.
Therefore, both HA-specific humoral immunity and cellular immunity play important
roles in the protection. These data suggest that the chimpanzee adenovirus
expressing HA is a promising vaccine candidate for H7N9 virus or other influenza
viral subtypes.
PMID- 28500342
TI - Controllability of complex networks with unilateral inputs.
AB - In this paper, we study the problem of controlling complex networks with
unilateral controls, i.e., controls which can assume only positive or negative
values, not both. Given a complex network represented by the adjacency matrix A,
an algorithm is developed that constructs an input matrix B such that the
resulting system (A, B) is controllable with a near minimal number of unilateral
control inputs. This is made possible by a reformulation of classical conditions
for controllability that casts the minimal unilateral input selection problem
into well known optimization problems. We identify network properties that make
unilateral controllability relatively easy to achieve as compared to unrestricted
controllability. The analysis of the network topology for instance allows us to
establish theoretical bounds on the minimal number of controls required. For
various categories of random networks as well as for a number of real-world
networks these lower bounds are often achieved by our heuristics.
PMID- 28500344
TI - Quantitative trait loci for large sink capacity enhance rice grain yield under
free-air CO2 enrichment conditions.
AB - The global atmospheric CO2 concentration has been increasing annually. To
determine the trait that effectively increases rice (Oryza sativa L.) grain yield
under increased atmospheric CO2 concentrations, as predicted in the near future,
we grew a chromosome segment substitution line (CSSL) and a near-isogenic line
(NIL) producing high spikelet numbers per panicle (CSSL-GN1 and NIL-APO1,
respectively) under free-air CO2 enrichment (FACE) conditions and examined the
effects of a large sink capacity on grain yield, its components, and growth
related traits under increased atmospheric CO2 concentrations. Under ambient
conditions, CSSL-GN1 and NIL-APO1 exhibited a similar grain yield to Koshihikari,
as a result of the trade-off between increased spikelet number and reduced grain
filling. However, under FACE conditions, CSSL-GN1 and NIL-APO1 had an equal or a
higher grain yield than Koshihikari because of the higher number of spikelets and
lower reduction in grain filling. Thus, the improvement of source activity by
increased atmospheric CO2 concentrations can lead to enhanced grain yield in rice
lines that have a large sink capacity. Therefore, introducing alleles that
increase sink capacity into conventional varieties represents a strategy that can
be used to develop high-yielding varieties under increased atmospheric CO2
concentrations, such as those predicted in the near future.
PMID- 28500341
TI - Determinants of neuroglobin plasticity highlighted by joint coarse-grained
simulations and high pressure crystallography.
AB - Investigating the effect of pressure sheds light on the dynamics and plasticity
of proteins, intrinsically correlated to functional efficiency. Here we detail
the structural response to pressure of neuroglobin (Ngb), a hexacoordinate globin
likely to be involved in neuroprotection. In murine Ngb, reversible coordination
is achieved by repositioning the heme more deeply into a large internal cavity,
the "heme sliding mechanism". Combining high pressure crystallography and coarse
grain simulations on wild type Ngb as well as two mutants, one (V101F) with
unaffected and another (F106W) with decreased affinity for CO, we show that Ngb
hinges around a rigid mechanical nucleus of five hydrophobic residues (V68, I72,
V109, L113, Y137) during its conformational transition induced by gaseous ligand,
that the intrinsic flexibility of the F-G loop appears essential to drive the
heme sliding mechanism, and that residue Val 101 may act as a sensor of the
interaction disruption between the heme and the distal histidine.
PMID- 28500343
TI - A genome scan for milk production traits in dairy goats reveals two new mutations
in Dgat1 reducing milk fat content.
AB - The quantity of milk and milk fat and proteins are particularly important traits
in dairy livestock. However, little is known about the regions of the genome that
influence these traits in goats. We conducted a genome wide association study in
French goats and identified 109 regions associated with dairy traits. For a major
region on chromosome 14 closely associated with fat content, the Diacylglycerol O
Acyltransferase 1 (DGAT1) gene turned out to be a functional and positional
candidate gene. The caprine reference sequence of this gene was completed and 29
polymorphisms were found in the gene sequence, including two novel exonic
mutations: R251L and R396W, leading to substitutions in the protein sequence. The
R251L mutation was found in the Saanen breed at a frequency of 3.5% and the R396W
mutation both in the Saanen and Alpine breeds at a frequencies of 13% and 7%
respectively. The R396W mutation explained 46% of the genetic variance of the
trait, and the R251L mutation 6%. Both mutations were associated with a notable
decrease in milk fat content. Their causality was then demonstrated by a
functional test. These results provide new knowledge on the genetic basis of milk
synthesis and will help improve the management of the French dairy goat breeding
program.
PMID- 28500346
TI - Structural studies of the periplasmic portion of the diguanylate cyclase CdgH
from Vibrio cholerae.
AB - Cyclic diguanylate monophosphate (c-di-GMP) is a second messenger involved in
bacterial signal transduction and produced by diguanylate cyclases (DGCs)
generally containing highly variable periplasmic signal-recognition domains. CdgH
is a DGC enzyme that regulates rugosity associated phenotypes in Vibrio cholerae.
CdgH has two N-terminal tandem periplasmic substrate-binding (PBPb) domains for
its signal recognition; however, the role of the tandem PBPb domains remains
unclear. Here, we reported the crystal structure of the periplasmic portion of
CdgH, which indicated that both tandem PBPb domains consist of typical interlobe
ligand-binding architecture. Unexpectedly, the PBPb-I domain binds an L-arginine
which apparently has been co-purified from the E. coli expression system, whereas
the PBPb-II domain is in an unliganded open state. Structural comparison with
other amino acid-binding proteins indicated that despite similar ligand-binding
pockets, the PBPb-I domain possesses two ligand-binding residues (E122 and Y148)
not conserved in homologs and involved in hydrophilic and hydrophobic
interactions with L-arginine. Isothermal titration calorimetry indicated that the
PBPb-I is primarily an L-arginine/L-lysine/L-ornithine-binding domain, whereas
the PBPb-II domain exhibits a preference for L-glutamine and L-histidine.
Remarkably, we found that the periplasmic portion of CdgH forms a stable dimer in
solution and L-arginine binding would cause conformational changes of the dimer.
PMID- 28500345
TI - Heterologous expression and characterization of functional mushroom tyrosinase
(AbPPO4).
AB - Tyrosinases are an ubiquitous group of copper containing metalloenzymes that
hydroxylate and oxidize phenolic molecules. In an application context the term
'tyrosinase' usually refers to 'mushroom tyrosinase' consisting of a mixture of
isoenzymes and containing a number of enzymatic side-activities. We describe a
protocol for the efficient heterologous production of tyrosinase 4 from Agaricus
bisporus in Escherichia coli. Applying this procedure a pure preparation of a
single isoform of latent tyrosinase can be achieved at a yield of 140 mg per
liter of autoinducing culture medium. This recombinant protein possesses the same
fold as the enzyme purified from the natural source as evidenced by single
crystal X-ray diffraction. The latent enzyme can be activated by limited
proteolysis with proteinase K which cleaves the polypeptide chain after K382,
only one The latent enzyme can amino acid before the main in-vivo activation
site. Latent tyrosinase can be used as obtained and enzymatic activity may be
induced in the reaction mixture by the addition of an ionic detergent (e.g. 2 mM
SDS). The proteolytically activated mushroom tyrosinase shows >50% of its maximal
activity in the range of pH 5 to 10 and accepts a wide range of substrates
including mono- and diphenols, flavonols and chalcones.
PMID- 28500347
TI - Novel Fabrication and Enhanced Photocatalytic MB Degradation of Hierarchical
Porous Monoliths of MoO3 Nanoplates.
AB - Porous monoliths of MoO3 nanoplates were synthesized from ammonium molybdate
(AHM) by freeze-casting and subsequent thermal treatment from 300 to 600 degrees
C. Pure orthorhombic MoO3 phase was obtained at thermal treatment temperature of
400 degrees C and above. MoO3 monoliths thermally treated at 400 degrees C
displayed bimodal pore structure, including large pore channels replicating the
ice crystals and small pores from MoO3 sheets stacking. Transmission electron
microscopy (TEM) images revealed that the average thicknesses of MoO3 sheet were
50 and 300 nm in porous monoliths thermally treated at 400 degrees C. The
photocatalytic performance of MoO3 was evaluated through degradation of methylene
blue (MB) under visible light radiation and MoO3 synthesized at 400 degrees C
exhibited strong adsorption performance and best photocatalytic activity for
photodegradation of MB of 99.7% under visible illumination for 60 min. MoO3
photocatalyst displayed promising cyclic performance, and the decolorization
efficiency of MB solution was 98.1% after four cycles.
PMID- 28500348
TI - Penicillinase-resistant antibiotics induce non-immune-mediated cholestasis
through HSP27 activation associated with PKC/P38 and PI3K/AKT signaling pathways.
AB - The penicillinase-resistant antibiotics (PRAs), especially the highly prescribed
flucloxacillin, caused frequent liver injury via mechanisms that remain largely
non-elucidated. We first showed that flucloxacillin, independently of
cytotoxicity, could exhibit cholestatic effects in human hepatocytes in the
absence of an immune reaction, that were typified by dilatation of bile
canaliculi associated with impairment of the Rho-kinase signaling pathway and
reduced bile acid efflux. Then, we analyzed the sequential molecular events
involved in flucloxacillin-induced cholestasis. A crucial role of HSP27 by
inhibiting Rho-kinase activity was demonstrated using siRNA and the specific
inhibitor KRIBB3. HSP27 activation was dependent on the PKC/P38 pathway, and led
downstream to activation of the PI3K/AKT pathway. Other PRAs induced similar
cholestatic effects while non PRAs were ineffective. Our results demonstrate that
PRAs can induce cholestatic features in human hepatocytes through HSP27
activation associated with PKC/P38 and PI3K/AKT signaling pathways and
consequently support the conclusion that in clinic they can cause a non-immune
mediated cholestasis that is not restricted to patients possessing certain
genetic determinants.
PMID- 28500349
TI - Quantitative Succinyl-Proteome Profiling of Camellia sinensis cv. 'Anji Baicha'
During Periodic Albinism.
AB - Lysine succinylation is a novel dynamic and evolutionarily conserved post
translational modification (PTM) that regulates various biological processes.
'Anji Baicha' is an albino tea variety that exhibits temperature-based
variability of leaf colour and amino acid concentrations. However, the mechanism
underlying albinism in 'Anji Baicha' has not been investigated at the level of
succinylation. Here, we identify 3530 lysine succinylation sites mapped to 2132
proteins in 'Anji Baicha', representing the first extensive data on the lysine
succinylome in the tea plant. Eleven conserved succinylation motifs were enriched
among the identified succinylated peptides. The protein-protein interaction maps
were visualized using Cytoscape software. Comparison across three typical
developmental stages of 'Anji Baicha' revealed that proteins exhibiting
differential succinylation levels were primarily involved in photosynthesis,
carbon fixation, biosynthesis of amino acids and porphyrin and chlorophyll
metabolism, suggesting that these succinylated proteins are involved in 'Anji
Baicha' leaf colour variability. These results not only deepen our understanding
of the mechanism underlying 'Anji Baicha' albinism and the regulatory role of
succinylation in the tea plant but also provide new insight into molecular
breeding for leaf colour variety.
PMID- 28500352
TI - Whole-mantle convection with tectonic plates preserves long-term global patterns
of upper mantle geochemistry.
AB - The evolution of the planetary interior during plate tectonics is controlled by
slow convection within the mantle. Global-scale geochemical differences across
the upper mantle are known, but how they are preserved during convection has not
been adequately explained. We demonstrate that the geographic patterns of
chemical variations around the Earth's mantle endure as a direct result of whole
mantle convection within largely isolated cells defined by subducting plates. New
3D spherical numerical models embedded with the latest geological paleo-tectonic
reconstructions and ground-truthed with new Hf-Nd isotope data, suggest that
uppermost mantle at one location (e.g. under Indian Ocean) circulates down to the
core-mantle boundary (CMB), but returns within >=100 Myrs via large-scale
convection to its approximate starting location. Modelled tracers pool at the CMB
but do not disperse ubiquitously around it. Similarly, mantle beneath the Pacific
does not spread to surrounding regions of the planet. The models fit global
patterns of isotope data and may explain features such as the DUPAL anomaly and
long-standing differences between Indian and Pacific Ocean crust. Indeed, the
geochemical data suggests this mode of convection could have influenced the
evolution of mantle composition since 550 Ma and potentially since the onset of
plate tectonics.
PMID- 28500350
TI - Formants provide honest acoustic cues to body size in American alligators.
AB - In many vertebrates, acoustic cues to body size are encoded in resonance
frequencies of the vocal tract ("formants"), rather than in the rate of tissue
vibration in the sound source ("pitch"). Anatomical constraints on the vocal
tract's size render formants honest cues to size in many bird and mammal species,
but it is not clear whether this correlation evolved convergently in these two
clades, or whether it is widespread among amniotes (mammals, birds, and non-avian
reptiles). We investigated the potential for honest acoustic cues in the bellows
of adult American alligators and found that formant spacing provided highly
reliable cues to body size, while presumed correlates of the source signal did
not. These findings held true for both sexes and for all bellows whether produced
in or out of water. Because birds and crocodilians are the last extant
Archosaurians and share common ancestry with all extinct dinosaurs, our findings
support the hypothesis that dinosaurs used formants as cues to body size. The
description of formants as honest signals in a non-avian reptile combined with
previous evidence from birds and mammals strongly suggests that the principle of
honest signalling via vocal tract resonances may be a broadly shared trait among
amniotes.
PMID- 28500351
TI - Non-Targeted Effects Models Predict Significantly Higher Mars Mission Cancer Risk
than Targeted Effects Models.
AB - Cancer risk is an important concern for galactic cosmic ray (GCR) exposures,
which consist of a wide-energy range of protons, heavy ions and secondary
radiation produced in shielding and tissues. Relative biological effectiveness
(RBE) factors for surrogate cancer endpoints in cell culture models and tumor
induction in mice vary considerable, including significant variations for
different tissues and mouse strains. Many studies suggest non-targeted effects
(NTE) occur for low doses of high linear energy transfer (LET) radiation, leading
to deviation from the linear dose response model used in radiation protection.
Using the mouse Harderian gland tumor experiment, the only extensive data-set for
dose response modelling with a variety of particle types (>4), for the first-time
a particle track structure model of tumor prevalence is used to investigate the
effects of NTEs in predictions of chronic GCR exposure risk. The NTE model led to
a predicted risk 2-fold higher compared to a targeted effects model. The scarcity
of data with animal models for tissues that dominate human radiation cancer risk,
including lung, colon, breast, liver, and stomach, suggest that studies of NTEs
in other tissues are urgently needed prior to long-term space missions outside
the protection of the Earth's geomagnetic sphere.
PMID- 28500354
TI - Assessment of Mine Water Quality Using Heavy Metal Pollution Index in a Coal
Mining Area of Damodar River Basin, India.
AB - A total no. of 16 mine water (underground and opencast coal mine pump discharges)
samples were collected from East Bokaro coalfield during pre-monsoon, monsoon and
post-monsoon seasons. The concentrations of Fe, Mn, Cu, Pb, Zn, Ni, As, Se, Al,
Cd and Cr were determined using inductively coupled plasma mass spectrometry for
the assessment of spatio-temporal variations, source apportionment and heavy
metal pollution indexing. The results demonstrated that concentrations of the
metals showed significant seasonality and most variables exhibited higher levels
in the pre-monsoon season. The principle component analysis for ionic source
identification was synthesized into three factors with eigen values cut off at
greater than unity and explained about 64.8% of the total variance. The extracted
factors seemed to be associated to the geogenic, extensive mining and allied
transportation sources of the elements. The heavy metal pollution index (HPI) of
the mine water calculated for the individual locations varied from 7.1 to 49.5.
Most of the locations fall under low to medium classes of HPI except few
locations which are under the influence of surface mining and associated
transportation.
PMID- 28500353
TI - Estimation of postmortem interval by vitreous potassium evaluation with a novel
fluorescence aptasensor.
AB - Estimation of postmortem interval (PMI) is a central role in medico-legal
identification. Analysis of vitreous potassium ions (K+) concentration is
frequently used by forensic workers to estimate PMI. This paper describes
interdisciplinary research to introduce fluorescence sensing techniques into
forensic medicine. On the basis of silver nanoclusters (AgNCs) probe stabilized
by DNA, a simple and highly sensitive fluorescence aptasensor has been proposed
to selectively detect K+ ions. The linear range for K+ ions was found to be 0.1
nM-1 mM, with limit of detection of 0.06 nM. Moreover, 63 vitreous humour cases
within 36 h after death were further studied to verify the utility of K+ ions in
estimating the PMI. By the fluorescence aptasensor method, a new formula was
built to determine the postmortem interval based on K+ ions concentration: PMI(h)
= -0.55 + 1.66 * CK+(r = 0.791). And the real significance of this research was
demonstrated by additional 6 cases with known PMIs. In comparison with the
conventional method, the presented aptasensor strategy is cost-effective and easy
in measuring vitreous K+, which may be potentially a better way for estimation of
PMI in medico-legal practice.
PMID- 28500356
TI - Intracameral cefuroxime in the prevention of postoperative endophthalmitis.
PMID- 28500355
TI - Fabrication of Metal-Organic Framework MOF-177 Coatings on Stainless Steel Fibers
for Head-Space Solid-Phase Microextraction of Phenols.
AB - Direct head-space solid-phase microextraction (HS-SPME) of phenols in water is
usually difficult due to its polarity and solubility in aqueous matrix. Herein we
report the fabrication of metal-organic framework MOF-177 coated stainless steel
fiber for the HS-SPME of phenols (2-methylolphenol, 4-methylolphenol, 2,4
dimethylolphenol, 2,4-dichlorphenol, and 3-methyl-4-chlorophenol) in
environmental water samples prior to the gas chromatography-mass spectrometry
detection. Several parameters affecting the extraction efficiency were optimized
in the experiment, including extraction temperature and time, the pH value and
salt addition. The results indicated that the coated fiber gave low detection
limits (0.015-0.043 MUg L-1) and good repeatability with the RSD ranging from
2.8% to 5.5% for phenols. The recoveries are between 84.5%-98.6% with the spiked
level of 10 MUg L-1 for the real water samples. The established method may afford
a kind of potential enrichment material and a reference method for the analysis
of methylphenols in water samples.
PMID- 28500357
TI - Lessons from a Community-Based Program to Monitor Forest Vertebrates in the
Brazilian Amazon.
AB - A large number of sustainable use reserves recently have been titled in the
Brazilian Amazonia. These reserves require public participation in the design and
implementation of management and monitoring programs. Species-monitoring programs
that engage local stakeholders may be useful for assessing wildlife status over
the long term. We collaborated on the development of a participatory program to
monitor forest vertebrates in the Piagacu-Purus Sustainable Development Reserve
and to build capacity among the local people. We examined relations between the
distance to the nearest human community and sighting rates of each species, and
evaluated the program overall. Eighteen wildlife monitors received training in
line transect and sign surveys and then conducted surveys along a total of ten
transects. Sighting rates of most species in the Piagacu-Purus Sustainable
Development Reserve were higher than those reported in other Amazonian forests.
Distance to the human community was not associated with the overall vertebrate
sighting rate. Use of the trained monitors was successful in terms of data
acquisition and engagement. The involvement of local people promoted discussions
about regulation of hunting in the reserve. Implementation of community-based
programs to monitor forest wildlife in Amazonian sustainable use reserves may
empower local communities and assess the status of wildlife through time.
PMID- 28500360
TI - Expert's comment concerning Grand Rounds case entitled "Thoracic osteotomy for
Gorham-Stout disease of the spine: a case report and literature review" by C.
Maillot et al., Eur Spine J: doi 10.1007/s00586-014-3613-3.
PMID- 28500358
TI - Injury prediction and vulnerability assessment using strain and susceptibility
measures of the deep white matter.
AB - Reliable prediction and diagnosis of concussion is important for its effective
clinical management. Previous model-based studies largely employ peak responses
from a single element in a pre-selected anatomical region of interest (ROI) and
utilize a single training dataset for injury prediction. A more systematic and
rigorous approach is necessary to scrutinize the entire white matter (WM) ROIs as
well as ROI-constrained neural tracts. To this end, we evaluated injury
prediction performances of the 50 deep WM regions using predictor variables based
on strains obtained from simulating the 58 reconstructed American National
Football League head impacts. To objectively evaluate performance, repeated
random subsampling was employed to split the impacts into independent training
and testing datasets (39 and 19 cases, respectively, with 100 trials). Univariate
logistic regressions were conducted based on training datasets to compute the
area under the receiver operating characteristic curve (AUC), while accuracy,
sensitivity, and specificity were reported based on testing datasets. Two tract
wise injury susceptibilities were identified as the best overall via pair-wise
permutation test. They had comparable AUC, accuracy, and sensitivity, with the
highest values occurring in superior longitudinal fasciculus (SLF; 0.867-0.879,
84.4-85.2, and 84.1-84.6%, respectively). Using metrics based on WM fiber strain,
the most vulnerable ROIs included genu of corpus callosum, cerebral peduncle, and
uncinate fasciculus, while genu and main body of corpus callosum, and SLF were
among the most vulnerable tracts. Even for one un-concussed athlete, injury
susceptibility of the cingulum (hippocampus) right was elevated. These findings
highlight the unique injury discriminatory potentials of computational models and
may provide important insight into how best to incorporate WM structural
anisotropy for investigation of brain injury.
PMID- 28500359
TI - Effect of including damage at the tissue level in the nonlinear homogenisation of
trabecular bone.
AB - Being able to predict bone fracture or implant stability needs a proper
constitutive model of trabecular bone at the macroscale in multiaxial, non
monotonic loading modes. Its macroscopic damage behaviour has been investigated
experimentally in the past, mostly with the restriction of uniaxial cyclic
loading experiments for different samples, which does not allow for the
investigation of several load cases in the same sample as damage in one direction
may affect the behaviour in other directions. Homogenised finite element models
of whole bones have the potential to assess complicated scenarios and thus
improve clinical predictions. The aim of this study is to use a homogenisation
based multiscale procedure to upscale the damage behaviour of bone from an
assumed solid phase constitutive law and investigate its multiaxial behaviour for
the first time. Twelve cubic specimens were each submitted to nine proportional
strain histories by using a parallel code developed in-house. Evolution of post
elastic properties for trabecular bone was assessed for a small range of
macroscopic plastic strains in these nine load cases. Damage evolution was found
to be non-isotropic, and both damage and hardening were found to depend on the
loading mode (tensile, compression or shear); both were characterised by linear
laws with relatively high coefficients of determination. It is expected that the
knowledge of the macroscopic behaviour of trabecular bone gained in this study
will help in creating more precise continuum FE models of whole bones that
improve clinical predictions.
PMID- 28500361
TI - [Live Animals and Staged Nature : Drawing and Photography in German Popular
Zoology between 1860 and 1910].
AB - It is the central thesis of this paper that the "biological perspective" (Lynn
Nyhart) typical for Germany, with its interest in living animals, not only
influenced natural history practices in many ways during the second half of the
19th century, rather also shaped the illustrations of popular zoology
publications, as for example those in Brehms Thierleben. The illustrators of this
period preferred to use live animals as models, which they studied in zoos. These
animals were often depicted in their "natural" habitats. Since the illustrators
knew only very little about these habitats, they had to be imagined. Another
fashionable genre within popular zoology was the portrayal of animals fighting,
which attracted attention because of their drama. The first wildlife
photographers oriented themselves on the zoological illustrations and, with the
aid of manipulation, staging and retouching, gave their photographs the
impression of natural surroundings and drama. Yet both the illustrators and the
photographers emphasized their truth to nature and - based on this - the
scientific value of their pictures. In so doing, they developed a "biological"
kind of wildlife photography, which, after the turn of the 19th century, allowed
dedicated amateurs to create a popular zoological oeuvre that was well received
by broad audiences.
PMID- 28500362
TI - MicroRNA-195 inhibits human gastric cancer by directly targeting basic fibroblast
growth factor.
AB - PURPOSE: Gastric cancer (GC) is one of the fatal malignancies worldwide with high
occurrences but poor outcomes. bFGF has been shown to play significant roles in
GC. Yet, whether bFGF affects the development of GC is less studied. METHODS:
MicroRNA assays, real-time PCR, and western blot were conducted for expression
analysis of miR-195-5p and basic fibroblast growth factor (bFGF). Luciferase
activity was measured with mutated bFGF 3'-UTR sequence at the 3' end of the
luciferase gene. Two GC cell lines, SNU-1 and KATO-3 overexpressing miR-195-5p
and bFGF were subjected to wound healing assay and transwell invasion assay.
Mouse GC xenograft model was established and subjected to tumor size analysis.
RESULTS: Expression levels of miR-195-5p and bFGF showed negative correlation in
human GC tissues. MiR-195-5p directly targeted bFGF 3'-UTR as demonstrated by
luciferase activity assay. MiR-195-5p, through downregulating bFGF, inhibited the
migration and invasion of SNU-1 and KATO-3 cells, as well as tumorigenesis in a
xenograft mouse model, which could be restored by re-introduction of bFGF.
CONCLUSIONS: MiR-195-5p inhibits tumorigenesis of GC through suppressing bFGF,
which supports both miR-195-5p and bFGF as potential therapeutic targets in the
treatment of GC.
PMID- 28500363
TI - Diffusion-weighted imaging of the kidneys in haemolytic uraemic syndrome.
AB - OBJECTIVES: To evaluate the kidneys of patients with haemolytic uraemic syndrome
(HUS) using diffusion-weighted imaging (DWI) and Doppler ultrasound (US) compared
with healthy controls. MATERIALS AND METHODS: Fifteen patients (mean age 33.3
years; three male; 12 female) with diarrhoea-positive HUS and 15 healthy
volunteers were prospectively evaluated with DWI and Doppler US. A total apparent
diffusion coefficient (ADCTOT), and ADCs predominantly reflecting microperfusion
(ADCLOW) and diffusion (ADCHIGH) were calculated. Doppler US evaluated renal
vascularity and flow. RESULTS: When compared with controls, kidneys affected by
HUS showed reduced cortical ADC values (ADCTOT 1.79+/-0.22 vs. 2.04+/-0.1x10-3
mm2/s, P 0.001), resulting in either low corticomedullary differences (11/15
patients) or an inverted corticomedullary pattern (4/15 patients). Reduction of
cortical ADC values was associated with a decrease of cortical vascularity on
Doppler US (ADCTOT, P<0.001; ADCLOW, P 0.047). Kidneys with complete absence of
the cortical vasculature on Doppler US (four patients) also demonstrated limited
diffusion (ADCHIGH, P 0.002). Low glomerular filtration rate, requirement for
haemodialysis during hospitalization, and longer duration of haemodialysis were
associated with decreased cortical diffusivity (ADCTOT: P 0.04, 0.007, and
<0.001, respectively). CONCLUSION: DWI shows qualitative and quantitative
abnormalities in kidneys affected by HUS, thereby extending the non-invasive
assessment of renal parenchymal damage. KEY POINTS: * In HUS, DWI is feasible for
functional characterization of kidney involvement. * Kidneys affected by HUS
showed reduced cortical diffusivity. * Decreased cortical diffusivity was
associated with lower kidney function. * Requirement and duration of
haemodialysis was linked to degree of cortical alterations.
PMID- 28500364
TI - Radiologists need to be aware of secondary central venous stenosis in patients
with SAPHO syndrome.
AB - OBJECTIVES: We aimed to define central venous stenosis (CVS) caused by
sternocostoclavicular hyperostosis as a feature of synovitis-acne-pustulosis
hyperostosis-osteitis (SAPHO) syndrome on routine contrast-enhanced computed
tomography (CT) images. The relationship between SAPHO syndrome and CVS without
venous thrombosis caused by anterior chest wall compression has not been
investigated. Therefore, the present study evaluated CVS in patients with SAPHO
syndrome at our hospital. METHODS: We retrospectively reviewed contrast-enhanced
CT images of ten patients with suspected or diagnosed SAPHO syndrome between
January 2007 and November 2015. The patients were assessed by contrast-enhanced
CT using 16-, 64- or 128-detector row scanners. Two radiologists independently
assessed the presence of CVS or obstruction and SAPHO syndrome in a retrospective
review of CT images. RESULTS: Six of the ten patients had findings of CVS with
SAPHO syndrome. The mean diameter and patency rate at the site of CVS were 1.88
mm and 27.2%, respectively. Stenosis was more significant in terms of the mean
diameter of CVS sites than of stenotic sites that crossed the anteroposterior
vein (p < 0.05). CONCLUSIONS: Radiologists who routinely assess contrast-enhanced
CT images should be aware that sternocostoclavicular hyperostosis with SAPHO
syndrome could cause secondary CVS. KEY POINTS: * SAPHO syndrome can cause
central venous stenosis. * Radiologists should consider central venous stenosis
in patients with SAPHO syndrome. * Early diagnosis of central venous stenosis due
to SAPHO syndrome is challenging.
PMID- 28500365
TI - Capsule, septum, and T2 hyperintense foci for differentiation between large
hepatocellular carcinoma (>=5 cm) and intrahepatic cholangiocarcinoma on
gadoxetic acid MRI.
AB - OBJECTIVE: To determine the added value of capsule, septum, and T2 hyperintense
foci for differentiating large hepatocellular carcinoma (HCC; >= 5 cm) from
intrahepatic cholangiocarcinoma (ICC) using gadoxetic acid MRI. METHODS: The
study included 116 patients (94 men, 22 women; mean age, 56.8 years) with
surgically confirmed HCCs (n = 87, 5.0-18.0 cm) or ICCs (n = 29, 5.0-14.0 cm) who
underwent gadoxetic acid MRI. Three observers independently reviewed MRIs in two
sessions, examining enhancement patterns only and then adding capsule, septum,
and T2 hyperintense foci. Reviewers used a five-point scale to score accuracy,
sensitivity, and specificity. RESULTS: A significant increase was observed in
accuracy when ancillary features (96.1-98.3%) were added compared to enhancement
pattern only (83.6-88.4%; p <= 0.02). Sensitivity was significantly increased
with combined reading (97.1-98.3%) compared to enhancement features only (81.6
88.5%; p <= 0.006) for two observers, with no difference in specificity (84.5
89.7% vs. 86.2-98.3%; p > 0.05). We found substantial to excellent interobserver
agreement for ancillary features (0.598-0.976). CONCLUSION: Adding capsule,
septum, and T2 hyperintense foci to enhancement patterns for gadoxetic acid MRI
increased diagnostic performance for characterizing large HCC by differentiating
it from ICC. KEY POINTS: * Capsule, septum, and T2 hyperintense foci were useful
for characterizing large HCC. * Adding ancillary features to enhancement pattern
increased accuracy for diagnosing large HCC. * Interobserver agreement was
substantial to excellent for ancillary features.
PMID- 28500366
TI - Comparison of 3D magnetic resonance imaging and digital subtraction angiography
for intracranial artery stenosis.
AB - OBJECTIVES: To compare three-dimensional high-resolution magnetic resonance
imaging (3D HR-MRI) and digital subtraction angiography (DSA) for diagnosing and
evaluating stenosis in the entire circle of Willis. METHODS: The study included
516 intracranial arteries from 43 patients with intracranial artery stenosis
(ICAS) who underwent both 3D HR-MRI and DSA within 1 month. Two readers
independently diagnosed atherosclerosis, dissection, moyamoya disease and
vasculitis, rated their diagnostic confidence for each vessel and measured the
luminal diameters. Reference standard was made from clinico-radiologic diagnosis.
Diagnostic accuracy, diagnostic confidence, the degree of stenosis and luminal
diameter were assessed and compared between both modalities. RESULTS: For
atherosclerosis, 3D HR-MRI showed better diagnostic accuracy (P = .03-.003),
sensitivity (P = .006-.01) and positive predictive value (P <= .001-.006)
compared to DSA. Overall, the readers were more confident of their diagnosis of
ICAS when using 3D HR-MRI (reader 1, P <= .001-.007; reader 2, P <= .001-.015).
3D HR-MRI showed similar degree of stenosis (P > .05) and higher luminal diameter
(P < .05) compared to DSA. CONCLUSIONS: 3D HR-MRI might be useful to evaluate
atherosclerosis, with better diagnostic confidence and comparable stenosis
measurement compared to DSA in the entire circle of Willis. KEY POINTS: * 3D HR
MRI showed better diagnostic accuracy for atherosclerosiscompared to DSA * 3D HR
MRI showed better overall diagnostic confidence for stenosiscompared to DSA * 3D
HR-MRI and DSA showed similar degree of stenosis.
PMID- 28500367
TI - Evolution of posterior fossa and brain morphology after in utero repair of open
neural tube defects assessed by MRI.
AB - OBJECTIVES: To describe characteristics of foetuses undergoing in utero repair of
open neural tube defects (ONTD) and assess postoperative evolution of posterior
fossa and brain morphology. METHODS: Analysis of pre- and postoperative foetal as
well as neonatal MRI of 27 foetuses who underwent in utero repair of ONTD. Type
and level of ONTD, hindbrain configuration, posterior fossa and liquor space
dimensions, and detection of associated findings were compared between MRI
studies and to age-matched controls. RESULTS: Level of bony spinal defect was
defined with exactness of +/- one vertebral body. Of surgically confirmed 18
myelomeningoceles (MMC) and 9 myeloschisis (MS), 3 MMC were misdiagnosed as MS
due to non-visualisation of a flat membrane on MRI. Hindbrain herniation was more
severe in MS than MMC (p < 0.001). After repair, hindbrain herniation resolved in
25/27 cases at 4 weeks and liquor spaces increased. While posterior fossa
remained small (p < 0.001), its configuration normalised. Lateral ventricle
diameter indexed to cerebral width decreased in 48% and increased in 12% of
cases, implying a low rate of progressive obstructive hydrocephalus. Neonatally
evident subependymal heterotopias were detected in 33% at preoperative and 50% at
postoperative foetal MRI. CONCLUSION: MRI demonstrates change of Chiari
malformation type II (CM-II) features. KEY POINTS: * Hindbrain herniation is
significantly more pronounced in myeloschisis than in myelomeningocele *
Resolution of hindbrain herniation 4 weeks after in utero closure of ONTD * MRI
is valuable for preoperative assessment and postoperative evaluation following in
utero repair.
PMID- 28500368
TI - Advanced myocardial tissue characterisation by a multi-component CMR protocol in
patients with rheumatoid arthritis.
AB - OBJECTIVES: Rheumatoid arthritis (RA) patients are at increased risk of suffering
from adverse cardiovascular events. Cardiovascular magnetic resonance (CMR)
mapping techniques might be appropriate tools to complement late gadolinium
enhancement (LGE) for the assessment of myocardial involvement. This study aimed
to perform advanced myocardial tissue characterisation in RA patients by a
multicomponent CMR protocol. METHODS: 22 RA patients were prospectively enrolled
and underwent CMR, including LGE and T1/T2 mapping sequences; 20 volunteers
served as controls. RESULTS: Mean LV-EF was 66%; prevalence of LGE was 18%. RA
patients had increased native T1 (985 vs. 959 ms, p = 0.03), expanded
extracellular volume (ECV) (27 vs. 25%, p = 0.02) and higher T2 values (52 vs. 49
ms, p < 0.001) compared to controls irrespective of the presence of LGE. T2
mapping showed the highest prevalence of values beyond the 95% percentile of
controls. CONCLUSION: RA patients demonstrated higher T1, ECV and T2 values
compared to controls, with most significant differences for T2. Since these
results seem to be independent of the presence of LGE, advanced myocardial tissue
characterisation including CMR mapping techniques in addition to LGE-CMR might be
useful in the evaluation of myocardial involvement in RA patients. KEY POINTS: *
RA patients had higher T1, ECV and T2 values compared to controls. * Most
significant differences were observed for T2. * Our results seem to be
independent of the presence of LGE. * Mapping might be useful in the evaluation
of myocardial involvement in RA.
PMID- 28500369
TI - Feature-tracking myocardial strain analysis in acute myocarditis: diagnostic
value and association with myocardial oedema.
AB - OBJECTIVES: To investigate the diagnostic value of cardiac magnetic resonance
(CMR) feature-tracking (FT) myocardial strain analysis in patients with suspected
acute myocarditis and its association with myocardial oedema. METHODS: Forty
eight patients with suspected acute myocarditis and 35 control subjects underwent
CMR. FT CMR analysis of systolic longitudinal (LS), circumferential (CS) and
radial strain (RS) was performed. Additionally, the protocol allowed for the
assessment of T1 and T2 relaxation times. RESULTS: When compared with healthy
controls, myocarditis patients demonstrated reduced LS, CS and RS values (LS:
19.5 +/- 4.4% vs. -23.6 +/- 3.1%, CS: -23.0 +/- 5.8% vs. -27.4 +/- 3.4%, RS: 28.9
+/- 8.5% vs. 32.4 +/- 7.4%; P < 0.05, respectively). LS (T1: r = 0.462, P <
0.001; T2: r = 0.436, P < 0.001) and CS (T1: r = 0.429, P < 0.001; T2: r = 0.467,
P < 0.001) showed the strongest correlations with T1 and T2 relaxations times.
Area under the curve of LS (0.79) was higher compared with those of CS (0.75; P =
0.478) and RS (0.62; P = 0.008). CONCLUSIONS: FT CMR myocardial strain analysis
might serve as a new tool for assessment of myocardial dysfunction in the
diagnostic work-up of patients suspected of having acute myocarditis. Especially,
LS and CS show a sufficient diagnostic performance and were most closely
correlated with CMR parameters of myocardial oedema. KEY POINTS: * Myocardial
strain measures are considerably reduced in patients with suspected myocarditis.
* Myocardial strain measures can sufficiently discriminate between diseased and
healthy patients. * Myocardial strain measures show basic associations with the
extent of myocardial oedema/inflammation.
PMID- 28500371
TI - The silhouette technique: improving post-operative radiographs for planning of
correction with a hexapod external fixator.
AB - Correction of deformity of a bone through use of a hexapod external fixator
requires clear definition of the relationship between the bone and the frame.
Achieving adequate orthogonal calibrated radiographs for this aim, with minimum X
ray exposure, can prove a challenge in the radiography suite. We describe a
simple technique for obtaining adequate imaging, without the use of additional
equipment. Introduction of the technique to our department has demonstrated an
improvement in the adequacy of planning radiographs and a reduction in the
requirement for repeat imaging.
PMID- 28500370
TI - Long-term prognostic performance of low-dose coronary computed tomography
angiography with prospective electrocardiogram triggering.
AB - OBJECTIVES: To assess long-term prognosis after low-dose 64-slice coronary
computed tomography angiography (CCTA) using prospective electrocardiogram
triggering. METHODS: We included 434 consecutive patients with suspected or known
coronary artery disease referred for low-dose CCTA. Patients were classified as
normal, with non-obstructive or obstructive lesions, or previously
revascularized. Coronary artery calcium score (CACS) was assessed in 223
patients. Follow-up was obtained regarding major adverse cardiac events (MACE):
cardiac death, myocardial infarction and elective revascularization. We performed
Kaplan-Meier analysis and Cox regressions. RESULTS: Mean effective radiation dose
was 1.7 +/- 0.6 mSv. At baseline, 38% of patients had normal arteries, 21% non
obstructive lesions, 32% obstructive stenosis and 8% were revascularized. Twenty
nine patients (7%) were lost to follow-up. After a median follow-up of 6.1 +/-
0.6 years, MACE occurred in 0% of patients with normal arteries, 6% with non
obstructive lesions, 30% with obstructive stenosis and 39% of those
revascularized. MACE occurrence increased with increasing CACS (P < 0.001), but
4% of patients with CACS = 0 experienced MACE. Multivariate Cox regression
identified obstructive stenosis, lesion burden in CCTA and CACS as independent
MACE predictors (P <= 0.001). CONCLUSION: Low-dose CCTA with prospective
electrocardiogram-triggering has an excellent long-term prognostic performance
with a warranty period >6 years for patients with normal coronary arteries. KEY
POINTS: * Coronary CT angiography (CCTA) has an excellent long-term prognostic
performance. * CCTA can accurately stratify cardiac risk according to coronary
lesion severity. * A normal CCTA predicts freedom from cardiac events for >6
years. * Patients with a coronary calcium score of 0 may experience cardiac
events. * CCTA allows for reclassification of cardiac risk compared with ESC
SCORE.
PMID- 28500372
TI - Ion mobility-mass spectrometry as a tool to investigate protein-ligand
interactions.
AB - Ion mobility-mass spectrometry (IM-MS) is a powerful tool for the simultaneous
analysis of mass, charge, size, and shape of ionic species. It allows the
characterization of even low-abundant species in complex samples and is therefore
particularly suitable for the analysis of proteins and their assemblies. In the
last few years even complex and intractable species have been investigated
successfully with IM-MS and the number of publications in this field is steadily
growing. This trend article highlights recent advances in which IM-MS was used to
study protein-ligand complexes and in particular focuses on the catch and release
(CaR) strategy and collision-induced unfolding (CIU). Graphical Abstract Native
mass spectrometry and ion mobility-mass spectrometry are versatile tools to
follow the stoichiometry, energetics, and structural impact of protein-ligand
binding.
PMID- 28500373
TI - Effects of varenicline versus transdermal nicotine replacement therapy on
cigarette demand on quit day in individuals with substance use disorders.
AB - RATIONALE: Cigarette demand is a behavioral economic measure of the relative
value of cigarettes. Decreasing the value of cigarette reinforcement may help
with quitting smoking. OBJECTIVES: This study aimed to evaluate the effects of
initial use of varenicline (VAR) versus nicotine replacement therapy (NRT) on
demand for cigarettes on quit day among smokers with substance use disorders
(SUD) and to determine whether reduced demand was associated with subsequent
abstinence from smoking at 1 and 3 months. METHODS: Participants (N = 110) were
randomized to double-blind, double-placebo conditions: VAR with placebo NRT or
NRT with placebo capsules. The cigarette purchase task (CPT) was used to assess
demand for cigarettes at baseline and on quit day, following a 1-week medication
dose run-up/placebo capsule lead-in and first day use of the patch. RESULTS:
Demand for cigarettes decreased from baseline to quit day without significant
differences between medications. Reductions in CPT intensity (number of
cigarettes that would be smoked if they were free) and CPT breakpoint (lowest
price at which no cigarettes would be purchased) predicted greater likelihood of
abstaining on quit day. Reduced intensity predicted length of abstinence at 1 and
3 months while reduced breakpoint predicted only 1 month length of abstinence.
CONCLUSIONS: Initial therapeutic doses of VAR and NRT resulted in similar
reductions in cigarette reinforcement. Larger initial reductions in demand on
quit day were associated with early success with abstaining from cigarettes.
Behavioral economic approaches may be useful for identifying individuals who
benefit less from pharmacotherapy and may need additional treatment resources.
TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT00756275.
PMID- 28500374
TI - Exploring the genetics of feed efficiency and feeding behaviour traits in a pig
line highly selected for performance characteristics.
AB - The consideration of feed efficiency traits is highly relevant in animal breeding
due to economic and ecologic impacts of the efficient usage and utilization of
feed resources. In pigs, corresponding observations are recorded using automatic
feeding stations and serve as one of the main criteria in most pig selection
programmes. Simultaneously, feeding stations also generate feeding behaviour data
which represent a nearly unused resource and provide a valuable proxy measure of
health status, animal welfare, and management practices. In the current study, an
integrated approach was applied to a feed efficiency tested and genome-wide
genotyped terminal sire line population. Therefore, genetic analyses were
performed combining a single-marker based approach and a Bayesian multi-marker
algorithm. Major quantitative trait loci (QTL) for feeding behaviour traits
comprising daily occupation time, daily feeder visit, and daily feeding rate were
identified on chromosomes 1, 4, 6, 7, 8, and 14. Feed efficiency was represented
by feed conversion ratio and daily feed intake revealing prominent genomic
regions on chromosomes 1, 6, 9, and 11. The positional and functional candidate
genes identified are involved in transport processes like AQP4, SLC22A23, and
SLC6A14 as well as energy sensing, generation, and utilization as exemplified by
PPP3CA, IQGAP3, ECI2, and DnaJC15. These molecular features provide the first
step towards the dissection of the genetic connection between distinct feeding
behaviour patterns, feed efficiency and performance, health, and welfare traits
driving the implementation of these traits in breeding programmes and pig
husbandry.
PMID- 28500375
TI - First molecular identification and genetic diversity of Strongyloides stercoralis
and Strongyloides fuelleborni in human communities having contact with long
tailed macaques in Thailand.
AB - The parasitic nematodes, Strongyloides stercoralis and Strongyloides fuelleborni,
can infect humans and non-human primates. We amplified and sequenced a portion of
the 18S ribosomal RNA gene (rRNA) and of the mitochondrial cytochrome c oxidase
subunit 1 (cox1) gene of Strongyloides from humans in the study area in Thailand,
where people have frequent contact with long-tailed macaques. Fresh stool samples
were obtained from 213 people and were examined using the agar plate culture
method. The overall prevalence of Strongyloides infection was 8.92% (19/213).
From a total of 19 worms (one per infected person), 18 adult males had 18S rRNA
sequences identical with that of S. stercoralis and one adult female had a
sequence almost identical with that of S. fuelleborni. A median-joining network
of cox1 sequences revealed nine new haplotypes from S. stercoralis, and an
overall haplotype diversity (Hd) of 0.9309. The single haplotype of S.
fuelleborni was also new and contributed to an overall haplotype diversity for
that species of 0.9842. This is the first molecular identification of S.
stercoralis and S. fuelleborni in a human community having contact with long
tailed macaques in Thailand. It is also the first report of S. fuelleborni
infecting a human in Thailand.
PMID- 28500376
TI - The PTPN22 R263Q polymorphism confers protection against systemic lupus
erythematosus and rheumatoid arthritis, while PTPN22 R620W confers susceptibility
to Graves' disease in a Mexican population.
AB - OBJECTIVE: The functional PTPN22 R620W polymorphism (rs2476601) is clearly
associated with susceptibility to several autoimmune diseases (ADs). However, the
PTPN22 R263Q polymorphism (rs33996649) has been scarcely explored in different
ADs. Here we aimed to examine the associations of the PTPN22 R620W and R263Q
polymorphisms with susceptibility to or protection against rheumatoid arthritis
(RA), systemic lupus erythematosus (SLE), and Graves' disease (GD) among Mexican
patients. METHODS: We conducted a case-control study including 876 patients (405
with SLE, 388 with RA, and 83 with GD) and 336 healthy control individuals.
PTPN22 genotypes were determined using the TaqMan 5' allele discrimination assay.
RESULTS: PTPN22 R620W was associated with GD susceptibility (OR 4.3, p = 0.004),
but was not associated with SLE (OR 1.8, p = 0.19). We previously demonstrated
that this polymorphism is associated with RA susceptibility (OR 4.17, p =
0.00036). Moreover, PTPN22 R263Q was associated with protection against SLE (OR
0.09, p = 004) and RA (OR 0.28, p = 0.045), but was not associated with GD.
CONCLUSIONS: Our data provide the first demonstration that PTPN22 R620W confers
GD susceptibility among Latin-American patients. Moreover, this is the second
report documenting the association of PTPN22 R263Q with protection against SLE
and RA.
PMID- 28500377
TI - Reliability of echocardiographic speckle-tracking derived bi-atrial strain
assessment under different hemodynamic conditions.
AB - The aim of this study was to assess intra- and inter-observer variability of left
(LA) and right atrial (RA) strain indices obtained by two-dimensional speckle
tracking echocardiography (2D-STE) in a healthy group of individuals at low
altitude and after rapid ascent to high-altitude in order to provoke altered
systemic and pulmonary hemodynamics otherwise seen in various cardiac diseases.
Twenty healthy subjects underwent transthoracic echocardiography during a
baseline examination at low-altitude (424 m) as well as 7, 20 and 44 h after
arrival at high-altitude (4559 m). Atrial strain indices (i.e. reservoir, conduit
and contractile strain) were determined off-line by two independent observers.
Intra- and inter-observer reproducibility of variables was assessed by intra
class correlation coefficients (ICCs), coefficients of variation and Bland Altman
plots. Heart rate, systemic blood pressure and pulmonary artery pressure
increased significantly from low-altitude to the first examination at high
altitude. Intra-observer ICCs were >=0.90 except for RA conduit strain with an
ICC of 0.86. The mean intra-observer differences were small and limits of
agreement of relative differences were narrow for all atrial strain parameters
(<3 and <16%, respectively). Inter-observer ICCs (0.80-0.90), mean biases and
limits of agreement (<4 and <20%, respectively) were greater than intra-observer
results for all parameters. Intra- and inter-obserer ICCs for all atrial strain
variables did not differ between low- and high-altitude. 2D-STE-derived bi-atrial
strain indices have excellent intra- and moderate inter-observer reproducibility
with no effect of high-altitude-induced hemodynamic changes on reliability
results.
PMID- 28500378
TI - Intravascular ultrasound elastography analysis of the elastic mechanical
properties of atherosclerotic plaque.
AB - To assess the elastic mechanical properties of atherosclerotic plaque with
different morphological properties by intravascular ultrasound elastography
(IVUSE). 30 purebred New Zealand rabbits were fed a high-cholesterol diet; the
abdominal aorta endothelium was balloon-injured after 2 weeks; at week 12, 2
plaques with moderate echo from each rabbit were chosen for in situ imaging, and
2 consecutive frames near the end-diastole images in situ were used to construct
an IVUS elastogram. Shear strain (SS) and area strain (AS) were greater for
eccentric than centripetal plaque (SS: 2.65(2.45)% vs. 1.79 +/- 0.97%, p < 0.05;
AS: 4.81(4.99)% vs. 3.23 +/- 1.75%, p < 0.05) but were lower with low than high
plaque burden (SS: 2.14 +/- 0.37% vs. 3.40 +/- 0.34%, p < 0.05; AS: 3.88 +/-
0.60% vs. 5.81 +/- 0.54%, p < 0.05). SS and AS were significantly greater for
plaque with negative than no remodeling (SS: 3.98 +/- 1.53% vs. 1.82(1.40)%, p <
0.017; AS: 6.94 +/- 2.24% vs. 2.59(2.87)%, p < 0.017) and were found correlated
with eccentric index and plaque burden (R2 = 0.365 and R2 = 0.359, both p <
0.05). Plaques associated with eccentricity, high plaque burden and negative
remodeling showed greater strain than those with centripetalism, low plaque
burden and positive remodeling. Eccentric index and plaque burden may be useful
to predict the elastic stability of plaque.
PMID- 28500380
TI - Association of T lymphocyte immune imbalance and IL-10 gene polymorphism with the
risk of obstructive sleep apnea in children with obesity.
AB - PURPOSE: The purpose of this study is to determine the role of T lymphocyte
immune imbalance and interleukin (IL)-10 gene polymorphism in the development of
obstructive sleep apnea (OSA) in obese children. METHODS: One hundred obese
children at high-risk and low-risk for OSA based upon a sleep questionnaire were
selected. Peripheral blood T lymphocyte subsets were measured by flow cytometry,
and plasma IFN-gamma, IL-4, and IL-10 cytokines were detected by ELISA. The
relationships between OSA and the above variables were analyzed. IL-10 gene
polymorphisms were analyzed by DNA sequencing. RESULTS: Ninety subjects completed
all the tests. Forty-two patients were diagnosed as OSA by PSG. Compared with non
OSA children, the levels of CD4+ T cells, IFN-gamma, and IL-4 were increased (P <
0.05) whereas the numbers of CD4+ CD25+ Treg and NKT cells and the levels of IL
10 were reduced (P < 0.05). Multiple linear regression analysis showed that IL-10
level was negatively associated with OAHI (OR 0.352, 95% CI 0.286-0.540; P <
0.05). In multivariate analysis, IL-10 also had a strong negative association
with OSA after adjustment for confounding factors from models 1 to 3. Correlative
analysis showed that IL-10 levels had a positive association with CD4+ CD25+ Treg
(r = 0.628, P < 0.01). Furthermore, the IL-10/A-1082G gene polymorphism
correlated with OSA. CONCLUSIONS: T lymphocyte immune imbalance was associated
with OSA and IL-10 may play an important protective role in the pathogenesis of
OSA in obese children.
PMID- 28500379
TI - Effect of zinc deprivation on the lipid metabolism of budding yeast.
AB - Zinc is an essential micronutrient for all living cells. It serves as a
structural and catalytic cofactor for numerous proteins, hence maintaining a
proper level of cellular zinc is essential for normal functioning of the cell.
Zinc homeostasis is sustained through various ways under severe zinc-deficient
conditions. Zinc-dependent proteins play an important role in biological systems
and limitation of zinc causes a drastic change in their expression. In budding
yeast, a zinc-responsive transcription factor Zap1p controls the expression of
genes required for uptake and mobilization of zinc under zinc-limiting
conditions. It also regulates the polar lipid levels under zinc-limiting
conditions to maintain membrane integrity. Deletion of ZAP1 causes an increase in
triacylglyerol levels which is due to the increased biosynthesis of acetate that
serves as a precursor for triacylglycerol biosynthesis. In this review, we
expanded our recent work role of Zap1p in nonpolar lipid metabolism of budding
yeast.
PMID- 28500381
TI - Radical change or warm sentiments? A commentary on Gronholm et al. (2017)
Interventions to reduce discrimination and stigma: the state of the art.
PMID- 28500382
TI - The football sign.
PMID- 28500383
TI - Quantitative assessment of the degree of differentiation in colon cancer with
dual-energy spectral CT.
AB - OBJECTIVE: To evaluate dual-energy spectral CT imaging in evaluating the degree
of differentiation in colon cancer. METHODS: Forty-seven colon cancer patients
underwent spectral CT during arterial phase (AP) and portal venous phase (PP),
and were characterized pathologically differentiated to well-differentiated (A, n
= 18) and poorly differentiated or undifferentiated carcinoma group (B, n = 29).
Lesion iodine concentration (IC) was measured and normalized to that of aorta
(NIC). CT numbers were measured and the slope (lambda HU) of the spectral HU
curve was calculated. These parameters were statistically compared between the
two groups. ROC curves were used to evaluate their diagnostic efficacies.
RESULTS: There were significant differences in IC (1.01 +/- 0.20 vs. 1.59 +/-
0.57 mg/ml), NIC (0.12 +/- 0.03 vs. 0.19 +/- 0.09), lambda HU (1.41 +/- 0.29 vs.
2.03 +/- 0.85), and CT number at 70 keV (48.61 +/- 9.03HU vs. 63.97 +/- 15.86HU)
between groups A and B in AP (p < 0.05), but no difference in PP. Using IC = 1.13
mg/ml in AP as the threshold, one obtained a sensitivity of 81.8% and a
specificity of 71.4% for differentiating well-differentiated from poorly
differentiated or undifferentiated carcinoma. These values were statistically
higher than those (64.7% and 62.3%) using CT number at 70 keV. CONCLUSION:
Spectral CT imaging parameters (IC, NIC, and lambda HU) in AP provide improved
accuracy for evaluating the degrees of differentiation in colon cancer than CT
number at 70 keV.
PMID- 28500385
TI - Assessment of the horizontal transfer of functional genes as a suitable approach
for evaluation of the bioremediation potential of petroleum-contaminated sites: a
mini-review.
AB - Petroleum sludge contains recalcitrant residuals. These compounds because of
being toxic to humans and other organism are of the major concerns. Therefore,
petroleum sludge should be safely disposed. Physicochemical methods which are
used by this sector are mostly expensive and need complex devices. Bioremediation
methods because of being eco-friendly and cost-effective overcome most of the
limitations of physicochemical treatments. Microbial strains capable to degrade
petroleum hydrocarbons are practically present in all soils and sediments and
their population density increases in contact with contaminants. Bacterial
strains cannot degrade alone all kinds of petroleum hydrocarbons, rather
microbial consortium should collaborate with each other for degradation of
petroleum hydrocarbon mixtures. Horizontal transfer of functional genes between
bacteria plays an important role in increasing the metabolic potential of the
microbial community. Therefore, selecting a suitable degrading gene and tracking
its horizontal transfer would be a useful approach to evaluate the bioremediation
process and to assess the bioremediation potential of contaminated sites.
PMID- 28500384
TI - Associations between social vulnerabilities and psychosocial problems in European
children. Results from the IDEFICS study.
AB - The effect of socioeconomic inequalities on children's mental health remains
unclear. This study aims to explore the cross-sectional and longitudinal
associations between social vulnerabilities and psychosocial problems, and the
association between accumulation of vulnerabilities and psychosocial problems.
5987 children aged 2-9 years from eight European countries were assessed at
baseline and 2-year follow-up. Two different instruments were employed to assess
children's psychosocial problems: the KINDL (Questionnaire for Measuring Health
Related Quality of Life in Children and Adolescents) was used to evaluate
children's well-being and the Strengths and Difficulties Questionnaire (SDQ) was
used to evaluate children's internalising problems. Vulnerable groups were
defined as follows: children whose parents had minimal social networks, children
from non-traditional families, children of migrant origin or children with
unemployed parents. Logistic mixed-effects models were used to assess the
associations between social vulnerabilities and psychosocial problems. After
adjusting for classical socioeconomic and lifestyle indicators, children whose
parents had minimal social networks were at greater risk of presenting
internalising problems at baseline and follow-up (OR 1.53, 99% CI 1.11-2.11). The
highest risk for psychosocial problems was found in children whose status changed
from traditional families at T0 to non-traditional families at T1 (OR 1.60, 99%
CI 1.07-2.39) and whose parents had minimal social networks at both time points
(OR 1.97, 99% CI 1.26-3.08). Children with one or more vulnerabilities
accumulated were at a higher risk of developing psychosocial problems at baseline
and follow-up. Therefore, policy makers should implement measures to strengthen
the social support for parents with a minimal social network.
PMID- 28500386
TI - Thermodynamics of enzyme-catalyzed esterifications: I. Succinic acid
esterification with ethanol.
AB - Succinic acid (SA) was esterified with ethanol using Candida antarctica lipase B
immobilized on acrylic resin at 40 and 50 degrees C. Enzyme activity in the
reaction medium was assured prior to reaction experiments. Reaction-equilibrium
experiments were performed for varying initial molalities of SA and water in the
reaction mixtures. This allowed calculating the molality-based apparent
equilibrium constant K m as function of concentration and temperature. K m was
shown to depend strongly on the molality of water and SA as well as on
temperature. It could be concluded that increasing the molality of SA shifted the
reaction equilibrium towards the products. Water had a strong effect on the
activity of the enzyme and on K m . The concentration dependence of K m values
was explained by the activity coefficients of the reacting agents. These were
predicted with the thermodynamic models Perturbed-Chain Statistical Associating
Fluid Theory (PC-SAFT), NRTL, and Universal Quasichemical Functional Group
Activity Coefficients (UNIFAC), yielding the ratio of activity coefficients of
products and reactants K gamma . All model parameters were taken from literature.
The models yielded K gamma values between 25 and 115. Thus, activity coefficients
have a huge impact on the consistent determination of the thermodynamic
equilibrium constants K th. Combining K m and PC-SAFT-predicted K gamma allowed
determining K th and the standard Gibbs energy of reaction as function of
temperature. This value was shown to be in very good agreement with results
obtained from group contribution methods for Gibbs energy of formation. In
contrast, inconsistencies were observed for K th using K gamma values from the
classical gE-models UNIFAC and NRTL. The importance of activity coefficients
opens the door for an optimized reaction setup for enzymatic esterifications.
PMID- 28500387
TI - Thermal adaptation strategies of the extremophile bacterium Thermus filiformis
based on multi-omics analysis.
AB - Thermus filiformis is an aerobic thermophilic bacterium isolated from a hot
spring in New Zealand. The experimental study of the mechanisms of thermal
adaptation is important to unveil response strategies of the microorganism to
stress. In this study, the main pathways involved on T. filiformis
thermoadaptation, as well as, thermozymes with potential biotechnological
applications were revealed based on omics approaches. The strategy adopted in
this study disclosed that pathways related to the carbohydrate metabolism were
affected in response to thermoadaptation. High temperatures triggered oxidative
stress, leading to repression of genes involved in glycolysis and the
tricarboxylic acid cycle. During heat stress, the glucose metabolism occurred
predominantly via the pentose phosphate pathway instead of the glycolysis
pathway. Other processes, such as protein degradation, stringent response, and
duplication of aminoacyl-tRNA synthetases, were also related to T. filiformis
thermoadaptation. The heat-shock response influenced the carotenoid profile of T.
filiformis, favoring the synthesis of thermozeaxanthins and thermobiszeaxanthins,
which are related to membrane stabilization at high temperatures. Furthermore,
antioxidant enzymes correlated with free radical scavenging, including superoxide
dismutase, catalase and peroxidase, and metabolites, such as oxaloacetate and
alpha-ketoglutarate, were accumulated at 77 degrees C.
PMID- 28500388
TI - Aspergillus atacamensis and A. salisburgensis: two new halophilic species from
hypersaline/arid habitats with a phialosimplex-like morphology.
AB - Halophilic fungal strains isolated from historical wooden staircase in a salt
mine in Austria, and from wall biofilm and soil of a cave in the Coastal Range of
the hyperarid Atacama Desert in Chile were characterised and described newly as
Aspergillus salisburgensis and Aspergillus atacamensis. Morphological characters
including solitary phialides producing solitary conidia and conidia in chains
and/or heads suggested affinity to Aspergillus subgenus Polypaecilum. Strains
required salt for growth, grew optimally on media with 10-25% NaCl and at 15-28
degrees C. These values are similar to those observed for Aspergillus salinarus
comb. nov. (Phialosimplex salinarum), while the ex-type strains of Aspergillus
sclerotialis, Aspergillus chlamydosporus and Aspergillus caninus (all belonging
to Aspergillus subgen. Polypaecilum) grew optimally at 0-5% NaCl and showed
fastest growth at 28-37 degrees C. Phylogenetic analyses on the basis of rDNA
sequences, RAPD-PCR fingerprint patterns, and cellobiohydrolase gene (cbh-I)
polymorphism clustered the strains into three groups and supported their
taxonomic recognition as A. salinarus, A. atacamensis and A. salisburgensis. On
the basis of phylogenetic inferences, also Sagenomella keratitidis is newly
combined as Aspergillus keratitidis and inferred as a species of Aspergillus
subgenus Polypaecilum.
PMID- 28500389
TI - Degradation of phospholipids under different types of irradiation and varying
oxygen saturation.
AB - The effects of different types of radiation on the formation of peroxide forms of
2-dioleoyl-sn-glycero-3-phosphocholine were studied under various conditions. For
the irradiation, an aqueous solution of small unilamellar vesicles was prepared.
Variations in parameters such as the dose rate and molecular oxygen saturation
levels were evaluated. Our study suggests that the mechanism of the peroxides
formation process remains unchanged under irradiation by accelerated electrons,
gamma and accelerated protons. The values of radiation chemical yields of the
peroxidic form depend on the type of radiation, dose rate, and the saturation of
molecular oxygen. The level of oxygen saturation strongly affects the values of
radiation chemical yields as well, as the dissolved oxygen is an important agent
participating in peroxidation and it is a source of free radicals during the
radiolysis. The values of radiation chemical yields strongly suggest that the
mechanism of radiation-induced peroxidation of phosphatidylcholines does not
proceed via chain reaction.
PMID- 28500391
TI - Anterior referencing of tibial slope in total knee arthroplasty considerably
influences knee kinematics: a musculoskeletal simulation study.
AB - PURPOSE: In total knee arthroplasty (TKA), the posterior tibial slope is not
always reconstructed correctly, and the knee ligaments may become too tight in
flexion. To release a tight flexion gap, surgeons can increase the posterior
tibial slope using two surgical resection techniques: the anterior tibial cortex
(ACR) or the centre of tibial plateau (CPR) referencing. It is not known how this
choice affects the knee laxity and function during activities of daily living.
The aim of this study was to investigate the effect of tibial slope on knee
laxity, kinematics and forces during a squatting activity using computer
simulation techniques. We hypothesised that the effects depend on the referencing
technique utilised. METHODS: A validated musculoskeletal model of TKA was used.
Knee laxity tests were simulated in flexion and extension. Then, a squat motion
was simulated to calculate: movement of the tibiofemoral joint (TFJ) contact
points and patello-femoral joint (PFJ) contact force. All analyses were repeated
with more anterior (-3 degrees ), neutral (0 degrees ), and more posterior tibial
slope (+3 degrees , +6 degrees , +9 degrees ), and with two referencing
techniques (ACR, CPR). RESULTS: Knee laxities increased dramatically with more
posterior slope with the ACR technique (up to 400%), both in flexion and in
extension. The CPR technique, instead, had much smaller effects (up to 42%
variations). During squatting, more slope with the ACR technique resulted in
larger movements of the TFJ contact point. The PFJ contact force decreased
considerably with more slope with the CPR technique (12% body weight reduction
every 3 degrees more posterior slope), thanks to the preservation of the
patellar height and quadriceps-femur load sharing. CONCLUSION: ACR technique
alters considerably the knee laxity, both in flexion and extensions, and surgeons
should be cautious about its use. More slope with CPR technique induces more
favourable TFJ kinematics and loading of the knee extensor apparatus and does not
substantially alter knee laxity. Preferably, the tibial slope resection should be
pre-planned thoroughly and performed using CPR technique as accurately as
possible. Surgeons can directly translate the results of this study into the
clinical practice.
PMID- 28500392
TI - A case of advanced gastric cancer achieved a pathological complete response by
chemotherapy.
AB - BACKGROUND: Although chemotherapy is the first recommended treatment of
unresectable gastric cancer, a pathological complete response is a rare event.
CASE PRESENTATION: A 58-year-old male was diagnosed as gastric cancer with a
bulky tumor, lymphadenopathy, and suspicious peritoneal dissemination. The
patient underwent chemotherapy with S-1 and cisplatin. After three courses of
chemotherapy, a computed tomography showed dramatic improvements in gastric wall
thickening, shrinkage of lymphadenopathy, and disappearance of disseminated
peritoneal lesion. The patient underwent potentially curative resection by total
gastrectomy with D2 lymph node dissection. Histological examination revealed the
absence of malignant cells not only in the resected specimen but also in the
harvested lymph nodes. At present, more than 7 years after the initial surgery,
the patient is still alive without any recurrence. CONCLUSIONS: We obtained a
pathological complete response by chemotherapy with S-1 and cisplatin for
advanced gastric cancer. Although a pathological complete response is a rare
event, it would be associated with the long-term survival of patients with
advanced gastric cancer.
PMID- 28500390
TI - Pollen exposure and hospitalization due to asthma exacerbations: daily time
series in a European city.
AB - Exposure to pollen can contribute to increased hospital admissions for asthma
exacerbation. This study applied an ecological time series analysis to examine
associations between atmospheric concentrations of different pollen types and the
risk of hospitalization for asthma in London from 2005 to 2011. The analysis
examined short-term associations between daily pollen counts and hospital
admissions in the presence of seasonal and long-term patterns, and allowed for
time lags between exposure and admission. Models were adjusted for temperature,
precipitation, humidity, day of week, and air pollutants. Analyses revealed an
association between daily counts (continuous) of grass pollen and adult hospital
admissions for asthma in London, with a 4-5-day lag. When grass pollen
concentrations were categorized into Met Office pollen 'alert' levels, 'very
high' days (vs. 'low') were associated with increased admissions 2-5 days later,
peaking at an incidence rate ratio of 1.46 (95%, CI 1.20-1.78) at 3 days.
Increased admissions were also associated with 'high' versus 'low' pollen days at
a 3-day lag. Results from tree pollen models were inconclusive and likely to have
been affected by the shorter pollen seasons and consequent limited number of
observation days with higher tree pollen concentrations. Future reductions in
asthma hospitalizations may be achieved by better understanding of environmental
risks, informing improved alert systems and supporting patients to take
preventive measures.
PMID- 28500393
TI - Association of serum microRNAs with islet autoimmunity, disease progression and
metabolic impairment in relatives at risk of type 1 diabetes.
AB - AIMS/HYPOTHESIS: MicroRNAs (miRNAs) are key regulators of gene expression and
novel biomarkers for many diseases. We investigated the hypothesis that serum
levels of some miRNAs would be associated with islet autoimmunity and/or
progression to type 1 diabetes. METHODS: We measured levels of 93 miRNAs most
commonly detected in serum. This retrospective cohort study included 150
autoantibody-positive and 150 autoantibody-negative family-matched siblings
enrolled in the TrialNet Pathway to Prevention Study. This was a young cohort
(mean age = 11 years), and most autoantibody-positive relatives were at high risk
because they had multiple autoantibodies, with 39/150 (26%, progressors)
developing type 1 diabetes within an average 8.7 months of follow-up. We analysed
miRNA levels in relation to autoantibody status, future development of diabetes
and OGTT C-peptide and glucose indices of disease progression. RESULTS: Fifteen
miRNAs were differentially expressed when comparing autoantibody
positive/negative siblings (range -2.5 to 1.3-fold). But receiver operating
characteristic (ROC) analysis indicated low specificity and sensitivity. Seven
additional miRNAs were differentially expressed among autoantibody-positive
relatives according to disease progression; ROC returned significant AUC values
and identified miRNA cut-off levels associated with an increased risk of disease
in both cross-sectional and survival analyses. Levels of several miRNAs showed
significant correlations (r values range 0.22-0.55) with OGTT outcomes. miR-21
3p, miR-29a-3p and miR-424-5p had the most robust associations.
CONCLUSIONS/INTERPRETATION: Serum levels of selected miRNAs are associated with
disease progression and confer additional risk of the development of type 1
diabetes in young autoantibody-positive relatives. Further studies, including
longitudinal assessments, are warranted to further define miRNA biomarkers for
prediction of disease risk and progression.
PMID- 28500394
TI - Bed rest and resistive vibration exercise unveil novel links between skeletal
muscle mitochondrial function and insulin resistance.
AB - AIMS/HYPOTHESIS: Physical inactivity has broad implications for human disease
including insulin resistance, sarcopenia and obesity. The present study tested
the hypothesis that (1) impaired mitochondrial respiration is linked with blunted
insulin sensitivity and loss of muscle mass in healthy young men, and (2)
resistive vibration exercise (RVE) would mitigate the negative metabolic effects
of bed rest. METHODS: Participants (n = 9) were maintained in energy balance
during 21 days of bed rest with RVE and without (CON) in a crossover study.
Mitochondrial respiration was determined by high-resolution respirometry in
permeabilised fibre bundles from biopsies of the vastus lateralis. A
hyperinsulinaemic-euglycaemic clamp was used to determine insulin sensitivity,
and body composition was assessed by dual-energy x-ray absorptiometry (DEXA).
RESULTS: Body mass (-3.2 +/- 0.5 kg vs -2.8 +/- 0.4 kg for CON and RVE,
respectively, p < 0.05), fat-free mass (-2.9 +/- 0.5 kg vs -2.7 +/- 0.5 kg, p <
0.05) and peak oxygen consumption ([Formula: see text]) (10-15%, p < 0.05) were
all reduced following bed rest. Bed rest decreased insulin sensitivity in the CON
group (0.04 +/- 0.002 mg kgFFM-1 [pmol l-1] min-1 vs 0.03 +/- 0.002 mg kgFFM-1
[pmol l-1] min-1 for baseline vs post-CON), while RVE mitigated this response
(0.04 +/- 0.003 mg kgFFM-1 [pmol l-1] min-1). Mitochondrial respiration
(oxidative phosphorylation and electron transport system capacity) decreased in
the CON group but not in the RVE group when expressed relative to tissue weight
but not when normalised for citrate synthase activity. LEAK respiration,
indicating a decrease in mitochondrial uncoupling, was the only component to
remain significantly lower in the CON group after normalisation for citrate
synthase. This was accompanied by a significant decrease in adenine nucleotide
translocase protein content. CONCLUSIONS/INTERPRETATION: Reductions in muscle
mitochondrial respiration occur concomitantly with insulin resistance and loss of
muscle mass during bed rest and may play a role in the adaptations to physical
inactivity. Significantly, we show that RVE is an effective strategy to partially
prevent some of the deleterious metabolic effects of bed rest.
PMID- 28500395
TI - The human serum protein C4b-binding protein inhibits pancreatic IAPP-induced
inflammasome activation.
AB - AIMS/HYPOTHESIS: Inflammasome activation and subsequent IL-1beta production is a
driver of islet pathology in type 2 diabetes. Oligomers, but not mature amyloid
fibrils, of human islet amyloid polypeptide (IAPP), which is co-secreted with
insulin, trigger NOD-like receptor pyrin domain containing-3 (NLRP3) inflammasome
activation. C4b-binding protein (C4BP), present in serum, binds to IAPP and
affects transition of IAPP monomers and oligomers to amyloid fibrils. We
therefore hypothesised that C4BP inhibits IAPP-mediated inflammasome activation
and IL-1beta production. METHODS: Macrophages were exposed to IAPP in the
presence or absence of plasma-purified human C4BP, and inflammasome activation
was assessed by IL-1beta secretion as detected by ELISA and reporter cell lines.
IAPP fibrillation was assessed by thioflavin T assay. Uptake of IAPP-C4BP
complexes and their effects on phagolysosomal stability were assessed by flow
cytometry and confocal microscopy. The effect of C4BP regulation of IAPP-mediated
inflammasome activation on beta cell function was assessed using a clonal rat
beta cell line. Immunohistochemistry was used to examine the association of IAPP
amyloid deposits and macrophage infiltration in isolated human and mouse
pancreatic islets, and expression of C4BP from isolated human pancreatic islets
was assessed by quantitative PCR, immunohistochemistry and western blot. RESULTS:
C4BP significantly inhibited IAPP-mediated IL-1beta secretion from primed
macrophages at physiological concentrations in a dose-dependent manner. C4BP
bound to and was internalised together with IAPP. C4BP did not affect IAPP uptake
into phagolysosomal compartments, although it did inhibit its formation into
amyloid fibrils. The loss of macrophage phagolysosomal integrity induced by IAPP
incubation was inhibited by co-incubation with C4BP. Supernatant fractions from
macrophages activated with IAPP inhibited both insulin secretion and viability of
clonal beta cells in an IL-1beta-dependent manner but the presence of C4BP during
macrophage IAPP incubation rescued beta cell function and viability. In human and
mouse islets, the presence of amyloid deposits correlated with higher numbers of
infiltrating macrophages. Isolated human islets expressed and secreted C4BP,
which increased with addition of IL-1beta. CONCLUSIONS/INTERPRETATION: IAPP
deposition is associated with inflammatory cell infiltrates in pancreatic islets.
C4BP blocks IAPP-induced inflammasome activation by preventing the loss of
macrophage phagolysosomal integrity required for NLRP3 activation. The
consequence of this is the preservation of beta cell function and viability. C4BP
is secreted directly from human pancreatic islets and this increases in response
to inflammatory cytokines. We therefore propose that C4BP acts as an
extracellular chaperone protein that limits the proinflammatory effects of IAPP.
PMID- 28500396
TI - SGLT2 inhibitors and diabetic ketoacidosis: data from the FDA Adverse Event
Reporting System.
AB - AIMS/HYPOTHESIS: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are
indicated for the treatment of type 2 diabetes and may also improve glucose
control in type 1 diabetes. In 2015, regulatory agencies warned that SGLT2i may
favour diabetic ketoacidosis (DKA). We provide a detailed analysis of DKA reports
in which an SGLT2i was listed among suspect or concomitant drugs in the US Food
and Drug Administration Adverse Event Reporting System (FAERS). METHODS: We first
analysed the entire public FAERS up to September (third quarter [Q3]) 2016 to
extract the number of reports, background indications and concomitant
medications, and to calculate proportional reporting ratios (PRRs) and safety
signals. We then mined single FAERS files from the first quarter (Q1) of 2014 to
2016 Q3 to obtain detailed information on DKA reports. RESULTS: The FAERS
database contains >2500 DKA reports in which SGLT2i are listed as suspect or
concomitant drugs. The PRR of DKA in reports including vs those not including an
SGLT2i and having a diabetes indication was 7.9 (95% CI 7.5, 8.4) and was higher
for type 1 diabetes. Several concomitant conditions were less prevalent in DKA
reports with SGLT2i vs DKA reports filed for other drugs. A detailed analysis of
2397 DKA reports for SGLT2i from 2014 Q1 to 2016 Q3 revealed a predominance of
women, an extremely wide range of age and body weight, and a highly variable
duration of SGLT2i treatment before onset of DKA. In 37 individuals (1.54%), DKA
was fatal. CONCLUSIONS/INTERPRETATION: Based on the profile of these reports,
SGLT2i-associated DKA may not be limited to any particular demographic or
comorbid subpopulation and can occur at any duration of SGLT2i use. DATA
AVAILABILITY: A list of FDA reports analysed in the study is available in the
figshare repository, 10.6084/m9.figshare.4903211 . Other data are available from
the corresponding author on reasonable request.
PMID- 28500397
TI - Analysis of lethal and sublethal impacts of environmental disasters on sperm
whales using stochastic modeling.
AB - Mathematical models are essential for combining data from multiple sources to
quantify population endpoints. This is especially true for species, such as
marine mammals, for which data on vital rates are difficult to obtain. Since the
effects of an environmental disaster are not fixed, we develop time-varying
(nonautonomous) matrix population models that account for the eventual recovery
of the environment to the pre-disaster state. We use these models to investigate
how lethal and sublethal impacts (in the form of reductions in the survival and
fecundity, respectively) affect the population's recovery process. We explore two
scenarios of the environmental recovery process and include the effect of
demographic stochasticity. Our results provide insights into the relationship
between the magnitude of the disaster, the duration of the disaster, and the
probability that the population recovers to pre-disaster levels or a biologically
relevant threshold level. To illustrate this modeling methodology, we provide an
application to a sperm whale population. This application was motivated by the
2010 Deepwater Horizon oil rig explosion in the Gulf of Mexico that has impacted
a wide variety of species populations including oysters, fish, corals, and
whales.
PMID- 28500399
TI - Childhood and teenage physical activity and breast cancer risk.
AB - PURPOSE: Adult physical activity is associated with reduced breast cancer risk,
but few studies have evaluated activity before adulthood. Early life may be an
important period because of rapid breast development and hormonal changes. This
study contributes new information by examining childhood (ages 5-12) and teenage
(ages 13-19) activity separately and overall. METHODS: The Sister Study is a
cohort of 50,884 women aged 35-74. Women reported age 5-19 sports/exercise
activities and age 10 and 16 unstructured activities. Both hours and MET-hours of
activity were considered in association with breast cancer overall, by ER status,
and by menopausal status. Hazard ratios (HRs) and 95% confidence intervals (CIs)
were calculated with Cox proportional hazards models. RESULTS: 2416 cases were
diagnosed during follow-up (mean = 6.4 years). Participation in 7+ hours (vs <1
h) per week of sports/exercise during ages 5-19 was associated with reduced
breast cancer risk (HR = 0.75; 95% CI 0.57-0.99). 7+ hours (vs <1 h) per week of
unstructured physical activity at age 16, but not age 10, was inversely
associated with breast cancer (HR = 0.81; 95% CI 0.70-0.95). Associations were
more pronounced for ER+ tumors, especially for activity during the childhood
(ages 5-12) period. Due to low correlation between childhood/teenage and
adulthood activity in this study (r = 0.1), it is unlikely that recent activity
explains our results. CONCLUSIONS: Findings from this large cohort indicate
higher levels of physical activity during ages 5-19 are inversely associated with
breast cancer risk, supporting early life as a window of susceptibility for
breast cancer development.
PMID- 28500398
TI - Comparative clinical utility of tumor genomic testing and cell-free DNA in
metastatic breast cancer.
AB - PURPOSE: Breast cancer metastases differ biologically from primary disease;
therefore, metastatic biopsies may assist in treatment decision making.
Commercial genomic testing of both tumor and circulating tumor DNA have become
available clinically, but utility of these tests in breast cancer management
remains unclear. METHODS: Patients undergoing a clinically indicated metastatic
tumor biopsy were consented to the ongoing METAMORPH registry. Tumor and blood
were collected at the time of disease progression before subsequent therapy, and
patients were followed for response on subsequent treatment. Tumor testing (n =
53) and concurrent cell-free DNA (n = 32) in a subset of patients was performed
using CLIA-approved assays. RESULTS: The proportion of patients with a genomic
alteration was lower in tumor than in blood (69 vs. 91%; p = 0.06). After
restricting analysis to alterations covered on both platforms, 83% of tumor
alterations were detected in blood, while 90% of blood alterations were detected
in tumor. Mutational load specific for the panel genes was calculated for both
tumor and blood. Time to progression on subsequent treatment was significantly
shorter for patients whose tumors had high panel-specific mutational load (HR
0.31, 95% CI 0.12-0.78) or a TP53 mutation (HR 0.35, 95% CI 0.20-0.79), after
adjusting for stage at presentation, hormone receptor status, prior treatment
type, and number of lines of metastatic treatment. CONCLUSIONS: Treating
oncologists must distinguish platform differences from true biological
heterogeneity when comparing tumor and cfDNA genomic testing results. Tumor and
concurrent cfDNA contribute unique genomic information in metastatic breast
cancer patients, providing potentially useful biomarkers for aggressive
metastatic disease.
PMID- 28500400
TI - Bioflocculation potentials of a uronic acid-containing glycoprotein produced by
Bacillus sp. AEMREG4 isolated from Tyhume River, South Africa.
AB - Bioflocculants are secondary metabolites produced by microorganisms during their
growth which have received attentions due to their biodegradability,
innocuousness and lack of secondary pollution from degradation intermediates.
This study reports on a bioflocculant produced by Bacillus specie isolated from
Thyume River in South Africa. The bacterial isolate was identified through 16S
rDNA sequencing and the BLAST analysis of the nucleotide sequences revealed 99%
similarity to Bacillus sp. BCT-7112. The sequence was subsequently deposited in
the GenBank as Bacillus sp. AEMREG4 with accession number KP406729. The optimum
culture conditions for bioflocculant production were an inoculum size 4% (v/v)
(80%) and starch (81%) as well as yeast extract (82%) as sole carbon and nitrogen
sources, respectively. Addition of Ca2+ greatly enhanced the flocculating
activity (76%) of crude bioflocculant over a wide range of pH 4-10 and retained
high flocculating activity when heated at 100 degrees C for 1 h. Chemical
analyses of the purified bioflocculant revealed carbohydrate (79% w/w) as a
predominant component followed by uronic acid (15% w/w) and protein (5% w/w).
Fourier transform infrared spectrum revealed the presence of carboxyl, hydroxyl
and methoxyl groups as the functional groups responsible for flocculation and the
high flocculation activity achieved portends its industrial applicability.
PMID- 28500401
TI - Sources of beta-galactosidase and its applications in food industry.
AB - The enzyme beta-galactosidases have been isolated from various sources such as
bacteria, fungi, yeast, vegetables, and recombinant sources. This enzyme holds
importance due to its wide applications in food industries to manufacture lactose
hydrolyzed products for lactose-intolerant people and the formation of
glycosylated products. Absorption of undigested lactose in small intestine
requires the activity of this enzyme; hence, the deficiency of this enzyme leads
to lactose intolerance. Lactose intolerance affects around 70% of world's adult
population, while the prevalence rate of lactose intolerance is 60% in Pakistan.
beta-Galactosidases are not only used to manufacture lactose-free products but
also employed to treat whey, and used in prebiotics. This review focuses on
various sources of beta-galactosidase and highlights the importance of beta
galactosidases in food industries.
PMID- 28500402
TI - Identification and characterization of a grain micronutrient-related OsFRO2 rice
gene ortholog from micronutrient-rich little millet (Panicum sumatrense).
AB - Minor millets are considered as nutrient-rich cereals having significant effect
in improving human health. In this study, a rice ortholog of Ferric Chelate
Reductase (FRO2) gene involved in plant metal uptake has been identified in iron
rich Little millet (LM) using PCR and next generation sequencing-based strategy.
FRO2 gene-specific primers designed from rice genome amplified 2.7 Kb fragment in
LM genotype RLM-37. Computational genomics analyses of the sequenced amplicon
showed high level sequence similarity with rice OsFRO2 gene. The predicted gene
structure showed the presence of 6 exons and 5 introns and its protein sequence
was found to contain ferric reductase and NOX_Duox_Like_FAD_NADP domains.
Further, 3D structure analysis of FCR-LM model protein (494 amino acids) shows
that it has 18 helices, 10 beta sheets, 10 strands, 41 beta turn and 5 gamma turn
with slight deviation from the FCR-Os structure. Besides, the structures of FCR
LM and FCR-Os were modelled followed by molecular dynamics simulations. The
overall study revealed both sequence and structural similarity between the
identified gene and OsFRO2. Thus, a putative ferric chelate reductase gene has
been identified in LM paving the way for using this approach for identification
of orthologs of other metal genes from millets. This also facilitates mining of
effective alleles of known genes for improvement of staple crops like rice.
PMID- 28500403
TI - Nanochitosan supports growth of Zea mays and also maintains soil health following
growth.
AB - The present study evaluated the effect of nanochitosan in combination with plant
growth promoting rhizobacteria (PGPR), PS2 and PS10 on maize growth. The PGPR
were earlier recognized as Bacillus spp. on the basis of 16S rDNA sequencing. The
observation revealed enhanced plant health parameters like seed germination (from
60 to 96.97%), plant height (1.5-fold increase), and leaf area (twofold).
Variability in different physicochemical parameters (pH, oxidizable organic
carbon, available phosphorous, available potassium, ammoniacal nitrogen and
nitrate nitrogen) was observed. Activities of soil health indicator enzymes
(dehydrogenase, fluorescein diacetate hydrolysis and alkaline phosphatase) were
also enhanced 2 to 3 fold. Plant metabolites with respect to different treatments
were also analyzed using gas chromatography-mass spectroscopy (GC-MS) and the
result revealed an increase in the amounts of alcohols, acid ester and aldehyde
compounds. Increase in organic acids indicates increased stress tolerance
mechanism operating in maize plant after treatment of nanochitosan.
PMID- 28500404
TI - Analysis of genetic structure and interrelationships in lentil species using
morphological and SSR markers.
AB - Genetic structure and relationships of 130 lentil accessions belonging to six
taxa were analysed. For this purpose, seven morphological traits and 31
polymorphic simple sequence repeat (SSR) primers were used for this purpose.
Morphological traits grouped lentil accessions into five main clusters. SSR
primers collectively amplified 139 polymorphic alleles in a range of 2-10 with an
average of 4.48 alleles. The size of amplified alleles varied from 50 to 650 bp.
Polymorphism information content (PIC) ranged from 0.02 to 0.85 with an average
of 0.46. Neighbour-joining tree grouped accessions broadly according to their
taxonomic ranks, except L. culinaris ssp. odemensis. Analysis of molecular
variance (AMOVA) revealed that a major portion (82.0%) of genetic variance
resided within species, while only 18% resided among species. Bayesian model
based STRUCTURE analysis assigned all accessions into five clusters and showed
some admixture within individuals. Cluster analysis showed that cultivated Lens
accessions of Ethiopian origin clustered separately, from other cultivated
accessions indicating its distinct lineage. Among the analysed lentil species, L.
culinaris ssp. odemensis seemed to have conserved genetic background and needs
revision of its taxonomic status. Results of present study provide important
information on genetic diversity and relationships among different wild and
cultivated taxa of lentil. Thus, these results can be useful in designing
breeding strategies for future improvement and taxonomic implications in lentil.
PMID- 28500405
TI - EST-SSR marker revealed effective over biochemical and morphological scepticism
towards identification of specific turmeric (Curcuma longa L.) cultivars.
AB - Turmeric (Curcuma longa L., family Zingiberaceae) is one of the most economically
important plants for its use in food, medicine, and cosmetic industries. Cultivar
identification is a major constraint in turmeric, owing to high degree of
morphological similarity that in turn, affects its commercialization. The present
study addresses this constraint, using EST-SSR marker based, molecular
identification of 8 elite cultivars and 88 accessions in turmeric. Fifty EST-SSR
primers were screened against eight cultivars of turmeric (Suroma, Roma,
Lakadong, Megha, Alleppey Supreme, Kedaram, Pratibha, and Suvarna); out of which
11 primers showed polymorphic banding pattern. The polymorphic information
content (PIC) of these primers ranged from 0.13 to 0.48. However, only three SSR
loci (CSSR 14, CSSR 15, and CSSR 18) gave reproducible unique banding pattern
clearly distinguishing the cultivars 'Lakadong' and 'Suvarna' from other
cultivars tested. These three unique SSR markers also proved to be effective in
identification of 'Lakadong' cultivars when analysed with 88 accessions of
turmeric collected from different agro-climatic regions. Furthermore, two
identified cultivars (Lakadong and Suvarna) could also be precisely
differentiated when analysed and based on phylogenetic tree, with other 94
genotypes of turmeric. The novel SSR markers can be used for identification and
authentication of two commercially important turmeric cultivars 'Lakadong' and
'Suvarna'.
PMID- 28500406
TI - Assessment of genetic diversity of sesame accessions collected from different
ecological regions using sequence-related amplified polymorphism markers.
AB - Sequence-related amplified polymorphism (SRAP) markers were used to assess the
genetic diversity among a collection of 52 sesame accessions representing
different geographical environments, including eight Saudi landraces. A
combination of seventeen primers generated a high number of alleles (365) with
100% polymorphism. The polymorphic information content (PIC) and primer
discrimination power (DP) recorded overall means of 0.88 and 5.88, respectively.
Genetic similarity values based on Jaccard coefficients ranged from 0.12 to 0.49,
with an average similarity value of 0.30, indicating both high genetic distance
and a wide genetic basis of the investigated accessions. The unweighted pair
group method with arithmetic mean (UPGMA) dendrogram grouped 48 of 52 accessions
into seven main clusters, and five accessions failed to form clusters and were
separated individually. However, subclusters separated the accessions and,
considering the relatedness of accessions and their geographical origin, formed
distinct diversity among groups. Saudi landraces showed the widest genetic basis
compared with other introduced accessions that were distributed throughout the
dendrogram, indicating that agro-ecological zones were indistinguishable by
cluster analysis. SRAP analysis revealed a high degree of genetic polymorphism in
sesame accessions investigated and showed weak association between geographical
origin and SRAP patterns. This wide genetic variability should be considered for
sesame breeding programs.
PMID- 28500407
TI - Phytochemical profile and free radical nitric oxide (NO) scavenging activity of
Averrhoa bilimbi L. fruit extract.
AB - Averrhoa bilimbi L. belongs to family Oxalidaceae. Traditionally, people use this
plant (root, bark, leaves and fruits) for treating several illnesses include
itches, boils, syphilis, whooping cough, hypertension, fever and inflammation.
The aim of the study was to evaluate the nitric oxide (NO) scavenging activity
and GC-MS analysis of A. bilimbi L. fruit extract. Averrhoa bilimbi L. fruits
were collected for the preliminary phytochemical analysis, antioxidant scavenging
activity and biologically important compounds were identified by GC-MS analysis.
The preliminary phytochemicals, GC-MS, total phenolic content and NO scavenging
activity of the plant were analysed. In the present investigation, the A. bilimbi
L. fruit extract has major phytochemicals. Among the 151 compounds identified in
GC-MS, 15 compounds are found to have diverse biological activity. We also
observed that the A. bilimbi L. fruit extract has high level of total phenolic
compounds at a concentration of 209.25 GAE mg/g. Presence of phenolic compound
apparently explains the antioxidant activity of the plant. Antioxidant activity
of A. bilimbi L. fruit extract is proven from its high level of NO scavenging
activity of potent IC50 value of 108.10. From the above study, it is apparent
that the A. bilimbi L. fruit extract is a rich source of phytochemicals (natural
products) with biological activity. The GC-MS report on this fruit proves that
natural products have pharmacologically and biologically active compounds. A high
phenolic content is observed in our study. A. bilimbi L. fruit extract is also
found to have NO scavenging activity in our study.
PMID- 28500408
TI - Scheduling internal medicine resident rotations to ensure fairness and facilitate
continuity of care.
AB - Completing a residency program is a requirement for medical students before they
can practice medicine independently. Residency programs in internal medicine must
undergo a series of supervised rotations in elective, inpatient, and ambulatory
units. Typically, a team of chief residents is charged to develop a yearly
rotational schedule. This process is complex, as it needs to consider academic,
managerial, regulatory, and legal restrictions while also facilitating the
provision of patient care, ensuring a diverse educational experience, balancing
the workload, and improving resident satisfaction. This study proposes (1) a
multi-stage multi-objective optimization approach for generating yearlong weekly
resident rotation schedules and (2) the use of Analytical Hierarchy Process (AHP)
to compare schedules across multiple criteria to select those that are more
equitable and hence to facilitate their adoption and implementation. Furthermore,
the proposed approach allows the scheduling of periodic clinic rotation schemes
that are commonly used to facilitate continuity of care, such as "4+1" or the
"8+2" policies. In the "4+1" policy residents rotate for four consecutive weeks
in different units prior to return for a week to a predetermined clinical post.
Similarly, in the "8+2" policy, residents rotate eight weeks across multiple
units before doing a two week rotation at a predetermined clinic.
PMID- 28500410
TI - Erratum to: Aldo-ketoreductase 1 (AKR1) improves seed longevity in tobacco and
rice by detoxifying reactive cytotoxic compounds generated during ageing.
PMID- 28500409
TI - Physicochemical and biological characteristics of BMP-2/IGF-1-loaded three
dimensional coaxial electrospun fibrous membranes for bone defect repair.
AB - Coaxial electrospun fibrous membranes show favorable mechanical properties for
use in guided bone regeneration (GBR). We used coaxial electrospinning technology
to fabricate three-dimensional nanofiber membranes loaded with BMP-2 and IGF-1,
and assessed the physicochemical and biological properties of these novel
membranes in vitro. We fabricated four experimental groups of BMP-2/IGF-1/BSA
loaded membranes with different flow ratios (shell/core). Membrane
characteristics were assessed by scanning and transmission electron microscopy,
and laser confocal microscopy. Physicochemical and drug release properties were
evaluated based on contact angle, mechanical property testing, X-ray diffraction
analysis, and ELISA. The membranes were seeded with bone marrow-derived
mesenchymal stem cells (BMMSCs) to estimate their biological properties based on
cell viability and alkaline phosphatase (ALP) activity. The four membrane groups
presented uniform diameters and core-shell structures. Acceleration of the shell
solution flow rate increased the contact angle and mechanical properties of the
fibrous membrane, while dual-factor addition did not impact fiber structure. Each
drug-loaded membrane showed a gradually increasing release curve, with varying
degrees of burst and sustained release. Compared to the other groups, the
membranes with a core-shell flow ratio of 1:10 showed better drug-loading
capacity and sustained release performance, higher biological properties and good
barrier function. Optimal parameters were chosen based on the physical and
chemical characteristics and biological properties of the membrane. Our results
imply that the BMP-2/IGF-1/BSA-loaded coaxial electrospun fibrous membrane with
optimum parameters is a suitable barrier membrane for GBR, and releases multiple
factors promoting osteoconduction and osteoinduction.
PMID- 28500411
TI - A hairy-leaf gene, BLANKET LEAF, of wild Oryza nivara increases photosynthetic
water use efficiency in rice.
AB - BACKGROUND: High water use efficiency is essential to water-saving cropping.
Morphological traits that affect photosynthetic water use efficiency are not well
known. We examined whether leaf hairiness improves photosynthetic water use
efficiency in rice. RESULTS: A chromosome segment introgression line (IL-hairy)
of wild Oryza nivara (Acc. IRGC105715) with the genetic background of Oryza
sativa cultivar 'IR24' had high leaf pubescence (hair). The leaf hairs developed
along small vascular bundles. Linkage analysis in BC5F2 and F3 populations showed
that the trait was governed by a single gene, designated BLANKET LEAF (BKL), on
chromosome 6. IL-hairy plants had a warmer leaf surface in sunlight, probably due
to increased boundary layer resistance. They had a lower transpiration rate under
moderate and high light intensities, resulting in higher photosynthetic water use
efficiency. CONCLUSION: Introgression of BKL on chromosome 6 from O. nivara
improved photosynthetic water use efficiency in the genetic background of IR24.
PMID- 28500412
TI - [Hereditary breast and ovarian cancer].
AB - Hereditary breast and ovarian carcinomas are frequently caused by germline
mutations of the BRCA1 and BRCA2 genes (BRCA1/2 syndromes) and are often less
associated with other hereditary syndromes such as Li-Fraumeni and Peutz-Jeghers.
The BRCA1/2 proteins have a special role in DNA repair. Therefore, loss of
function due to mutation causes an accumulation of mutations in other genes and
subsequent tumorigenesis at an early age. BRCA1/2 mutations are irregularly
distributed over the length of the genes without hot spots, although special
mutations are known. Breast and ovarian cancer occur far more frequently in women
with BRCA1/2 germline mutations compared with the general population. Breast
cancer occurs increasingly from the age of 30, ovarian cancer in BRCA1 syndrome
from the age of 40 and BRCA2 from the age of 50. Suspicion of a BRCA syndrome
should be prompted in the case of clustering of breast cancer in 1st degree
relatives, in particular at a young age, if breast and ovarian cancer have
occurred, and if cases of male breast cancer are known. Breast carcinomas with
medullary differentiation seem to predominate in BRCA syndromes, but other
carcinoma types may also occur. BRCA germline mutations seem to occur frequently
in triple-negative breast carcinomas, whereas an association with ductal
carcinoma in situ (DCIS) is rare. Ovarian carcinomas in BRCA syndromes are
usually high-grade serous, mucinous carcinomas and borderline tumors are unusual.
Pathology plays a special role within the multidisciplinary team in the
recognition of patients with hereditary cancer syndromes.
PMID- 28500414
TI - Comparative Metabolomic Analysis of the Green Microalga Chlorella sorokiniana
Cultivated in the Single Culture and a Consortium with Bacteria for Wastewater
Remediation.
AB - Co-culture of microalgae with many types of bacteria usually comes out with
significant different treatment efficiencies for COD, nitrogen, and phosphorus in
wastewater remediation, compared with the single culture. In order to understand
the mechanism behind, a comparative experiment was designed in this study, using
the green microalgae species Chlorella sorokiniana in the single culture and a
consortium with a bacterium, Pseudomonas H4, for nutrient removal. Comparative
metabolome profile analysis was conducted to reveal the Chlorella cell responses
to the synergistic growth with the bacteria, and possible relations between the
metabolic regulation of microalgae and the nutrient degradation were discussed.
The detectable differential metabolites of Chlorella belonged to several classes,
including carbohydrates, fatty acids, amino acids, phosphates, polyols, etc. The
orthogonal partial least squares discriminant analysis (OPLS-DA) model of the
identified metabolites suggests the metabolism in this alga was significantly
affected by the bacteria, corresponding to different treatment behaviors.
PMID- 28500413
TI - Impaired Pulmonary Function is an Additional Potential Mechanism for the
Reduction of Functional Capacity in Clinically Stable Fontan Patients.
AB - Central factors negatively affect the functional capacity of Fontan patients
(FP), but "non-cardiac" factors, such as pulmonary function, may contribute to
their exercise intolerance. We studied the pulmonary function in asymptomatic FP
and its correlations with their functional capacity. Pulmonary function and
cardiopulmonary exercise tests were performed in a prospective study of 27 FP and
27 healthy controls (HC). Cardiovascular magnetic resonance was used to evaluate
the Fontan circulation. The mean age at tests, the mean age at surgery, and the
median follow-up time of FP were 20(+/-6), 8(+/-3), and 11(8-17) years,
respectively. Dominant ventricle ejection fraction was within normal range. The
mean of peak VO2 expressed in absolute values (L/min), the relative values to
body weight (mL/kg/min), and their predicted values were lower in FP compared
with HC: 1.69 (+/-0.56) vs 2.81 (+/-0.77) L/min; 29.9 (+/-6.1) vs 41.5 (+/-9.3)
mL/kg/min p < 0.001 and predicted VO2 Peak [71% (+/-14) vs 100% (+/-20) p <
0.001]. The absolute and predicted values of the forced vital capacity (FVC),
forced expiratory volume in one second (FEV1), inspiratory capacity (IC), total
lung capacity (TLC), diffusion capacity of carbon monoxide of the lung (DLCO),
maximum inspiratory pressure (MIP), and sniff nasal inspiratory pressure (SNIP)
were also significantly lower in the Fontan population compared to HC. An
increased risk of restrictive ventilatory pattern was found in patients with
postural deviations (OD:10.0, IC:1.02-97.5, p = 0.042). There was a strong
correlation between pulmonary function and absolute peak VO2 [FVC (r = 0.86, p <
0.001); FEV1 (r = 0.83, p < 0.001); IC (r = 0.84, p < 0.001); TLC (r = 0.79, p <
0.001); and DLCO (r = 0.72, p < 0.001). The strength of the inspiratory muscles
in absolute and predicted values was also reduced in FP [-79(+/-28) vs -109(+/
44) cmH2O (p = 0.004) and 67(+/-26) vs 89(+/-36) % (p = 0.016)]. Thus, we
concluded that the pulmonary function was impaired in clinically stable Fontan
patients and the static and dynamic lung volumes were significantly reduced
compared with HC. We also demonstrated a strong correlation between absolute Peak
VO2 with the FVC, FEV1, TLC, and DLCO measured by complete pulmonary test.
PMID- 28500415
TI - Mind-muscle connection training principle: influence of muscle strength and
training experience during a pushing movement.
AB - PURPOSE: To investigate the effect of different attentional focus conditions on
muscle activity during the push-up exercise and to assess the possible influence
of muscle strength and training experience. METHODS: Eighteen resistance-trained
men performed 1RM bench press testing and were familiarized with the procedure
during the first session. In the second session, three different conditions were
randomly performed: regular push-up and push-up focusing on using the pectoralis
major and triceps brachii muscles, respectively. Surface electromyography (EMG)
was recorded and analyzed (EMG normalized to max; nEMG) for the triceps brachii
and pectoralis major muscles. RESULTS: Participants had on average 8 (SD 6) years
of training experience and 1RM of 1.25 (SD 0.28) kg per kg bodyweight. Focusing
on using pectoralis major increased activity in this muscle by 9% nEMG (95% CI 5
13; Cohen's d 0.60) compared with the regular condition. Triceps activity was not
significantly influenced by triceps focus although borderline significant, with a
mean difference of 5% nEMG (95% CI 0-10; Cohen's d 0.30). However, years of
training experience was positively associated with the ability to selectively
activate the triceps (beta = 0.41, P = 0.04), but not the pectoralis. Bench press
1RM was not significantly associated with the ability to selectively activate the
muscles. CONCLUSION: Pectoralis activity can be increased when focusing on using
this muscle during push-ups, whereas the ability to do this for the triceps is
dependent on years of training experience. Maximal muscle strength does not
appear to be a decisive factor for the ability to selectively activate these
muscles.
PMID- 28500416
TI - Effects of breaking up prolonged sitting following low and high glycaemic index
breakfast consumption on glucose and insulin concentrations.
AB - PURPOSE: Breaking up prolonged sitting can attenuate the postprandial rise in
glucose and insulin. Whether such effects are dependent of the glycaemic index
(GI) of the consumed carbohydrate is unknown. This study examined the acute
effects of breaking up prolonged sitting following a low GI and a high GI
breakfast on postprandial glucose and insulin concentrations. PROCEDURES:
Fourteen adult males aged 22.1 +/- 1.2 years completed four, 4 h experimental
conditions: high GI breakfast followed by uninterrupted sitting (HGI-SIT), low GI
breakfast followed by uninterrupted sitting (LGI-SIT), high GI breakfast followed
by 2 min activity breaks every 20 min (HGI-ACT), and low GI breakfast followed by
2 min activity breaks every 20 min (LGI-ACT). Positive incremental area under the
curve (iAUC) for glucose and insulin (mean [95% CI]) for each 4 h experimental
condition was calculated. Statistical analyses were completed using linear mixed
models. RESULTS: The sitting * breakfast GI interaction was not significant for
glucose positive iAUC (P = 0.119). Glucose positive iAUC (mmol/L 4 h-1) was
significantly lower in the activity breaks conditions than the uninterrupted
sitting conditions (2.07 [2.24, 2.89] vs. 2.56 [1.74, 2.40], respectively, P =
0.004) and significantly lower in the low GI conditions than the high GI
conditions (2.13 [1.80, 2.45] vs. 2.51 [2.18, 2.84], respectively, P = 0.022).
Insulin concentrations did not differ between conditions (P >= 0.203).
CONCLUSIONS: Breaking up prolonged sitting and lowering breakfast GI
independently reduced postprandial glucose responses. This indicates that
interrupting prolonged sitting and reducing dietary GI are beneficial approaches
for reducing cardiometabolic disease risk.
PMID- 28500418
TI - Weight Loss After Bariatric Surgery: Do Clinical and Behavioral Factors Explain
Racial Differences?
AB - BACKGROUND: Prior studies have suggested less weight loss among African American
compared to Caucasian patients; however, few studies have been able to
simultaneously account for baseline differences in other demographic, clinical,
or behavioral factors. METHODS: We interviewed patients at two weight loss
surgery (WLS) centers and conducted chart reviews before and after WLS. We
compared weight loss post-WLS by race/ethnicity and examined baseline
demographic, clinical (BMI, comorbidities, quality of life), and behavioral
(eating behavior, physical activity level, alcohol intake) factors that might
explain observed racial differences in weight loss at 1 and 2 years after WLS.
RESULTS: Of 537 participants who underwent either Roux-en-Y Gastric Bypass (54%)
or gastric banding (46%), 85% completed 1-year follow-up and 73% completed 2-year
follow-up. Patients lost a mean of 33.00% of initial weight at year 1 and 32.43%
at year 2 after bypass and 16.07% and 17.56 % respectively after banding. After
adjustment for other demographic characteristics and type of surgery, African
Americans lost an absolute 5.93 +/- 1.49% less weight than Caucasian patients
after bypass (p < 0.001) and 4.72 +/- 1.96% less weight after banding. Of the
other demographic, clinical, behavioral factors considered, having diabetes and
perceived difficulty making dietary changes at baseline were associated with less
weight loss among gastric bypass patients whereas having a diagnosis of anxiety
disorder was associated with less weight loss among gastric banding patients. The
association between race and weight loss did not substantially attenuate with
additional adjustment for these clinical and behavioral factors, however.
CONCLUSION: African American patients lost significantly less weight than
Caucasian patients. Racial differences could not be explained by baseline
demographic, clinical, or behavioral characteristics we examined.
PMID- 28500419
TI - Bariatric Surgery as a Bridge to Renal Transplantation in Patients with End-Stage
Renal Disease.
AB - BACKGROUND: Obesity is a relative contraindication to organ transplantation.
Preliminary reports suggest that bariatric surgery may be used as a bridge to
transplantation in patients who are not eligible for transplantation because of
morbid obesity. SETTING: The Bariatric Center at Tampa General Hospital,
University of South Florida, Tampa, Florida. METHODS: We reviewed the outcomes of
16 consecutive patients on hemodialysis for end-stage renal disease (ESRD) who
underwent bariatric surgery from 1998 to 2016. Demographics, comorbidities,
weight loss, as well as transplant status were reported. Data is mean +/- SD.
RESULTS: Six men and ten women aged 43-66 years (median = 54 years) underwent
laparoscopic Roux-en-Y gastric bypass (LRYGB, n = 12), laparoscopic adjustable
gastric banding (LAGB, n = 3), or laparoscopic sleeve gastrectomy (LSG, n = 1).
Preoperative BMI was 48 +/- 8 kg/m2. Follow-up to date was 1-10 years (median =
2.8 years); postoperative BMI was 31 +/- 7 kg/m2; %EBWL was 62 +/- 24. Four
patients underwent renal transplantation (25%) between 2.5-5 years after
bariatric surgery. Five patients are currently listed for transplantation. Five
patients were not listed for transplantation due to persistent comorbidities; two
of these patients died as a consequence of their comorbidities (12.5%) more than
1 year after bariatric surgery. Two patients were lost to follow-up (12.5%).
CONCLUSION: Bariatric surgery is effective in patients with ESRD and improves
access to renal transplantation. Bariatric surgery offers a safe approach to
weight loss and improvement in comorbidities in the majority of patients.
Referrals of transplant candidates with obesity for bariatric surgery should be
considered early in the course of ESRD.
PMID- 28500417
TI - Pathophysiology and Treatment of Memory Dysfunction After Traumatic Brain Injury.
AB - Memory is fundamental to everyday life, and cognitive impairments resulting from
traumatic brain injury (TBI) have devastating effects on TBI survivors. A
contributing component to memory impairments caused by TBI is alteration in the
neural circuits associated with memory function. In this review, we aim to bring
together experimental findings that characterize behavioral memory deficits and
the underlying pathophysiology of memory-involved circuits after TBI. While there
is little doubt that TBI causes memory and cognitive dysfunction, it is difficult
to conclude which memory phase, i.e., encoding, maintenance, or retrieval, is
specifically altered by TBI. This is most likely due to variation in behavioral
protocols and experimental models. Additionally, we review a selection of
experimental treatments that hold translational potential to mitigate memory
dysfunction following injury.
PMID- 28500420
TI - Purification, biochemical, and structural characterization of a novel
fibrinolytic enzyme from Mucor subtilissimus UCP 1262.
AB - Fibrinolytic proteases are enzymes that degrade fibrin. They provide a promising
alternative to existing drugs for thrombolytic therapy. A protease isolated from
the filamentous fungus Mucor subtilissimus UCP 1262 was purified in three steps
by ammonium sulfate fractionation, ion exchange, and molecular exclusion
chromatographies, and characterized biochemically and structurally. The purified
protease exhibited a molecular mass of 20 kDa, an apparent isoelectric point of
4.94 and a secondary structure composed mainly of alpha-helices. Selectivity for
N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide as substrate suggests that this enzyme
is a chymotrypsin-like serine protease, whose activity was enhanced by the
addition of Cu2+, Mg2+, and Fe2+. The enzyme showed a fibrinolytic activity of
22.53 U/mL at 40 degrees C and its contact with polyethylene glycol did not lead
to any significant alteration of its secondary structure. This protein represents
an important example of a novel fibrinolytic enzyme with potential use in the
treatment of thromboembolic disorders such as strokes, pulmonary emboli, and deep
vein thrombosis.
PMID- 28500422
TI - Are Reptiles Reservoirs of Leptospirosis? A Brief Discussion Based on Serological
Studies.
PMID- 28500421
TI - Seasonal Fluctuations of Astrovirus, But Not Coronavirus Shedding in Bats
Inhabiting Human-Modified Tropical Forests.
AB - Emerging infectious diseases (EIDs) are considered a major threat to global
health. Most EIDs appear to result from increased contact between wildlife and
humans, especially when humans encroach into formerly pristine habitats. Habitat
deterioration may also negatively affect the physiology and health of wildlife
species, which may eventually lead to a higher susceptibility to infectious
agents and/or increased shedding of the pathogens causing EIDs. Bats are known to
host viruses closely related to important EIDs. Here, we tested in a
paleotropical forest with ongoing logging and fragmentation, whether habitat
disturbance influences the occurrence of astro- and coronaviruses in eight bat
species. In contrast to our hypothesis, anthropogenic habitat disturbance was not
associated with corona- and astrovirus detection rates in fecal samples. However,
we found that bats infected with either astro- or coronaviruses were likely to be
coinfected with the respective other virus. Additionally, we identified two more
risk factors influencing astrovirus shedding. First, the detection rate of
astroviruses was higher at the beginning of the rainy compared to the dry season.
Second, there was a trend that individuals with a poor body condition had a
higher probability of shedding astroviruses in their feces. The identification of
risk factors for increased viral shedding that may potentially result in
increased interspecies transmission is important to prevent viral spillovers from
bats to other animals, including humans.
PMID- 28500424
TI - Cardiac surgery-associated acute kidney injury: tools for enriching clinical
trial populations.
PMID- 28500423
TI - Physiological Self-Regulation Buffers the Relationship between Impulsivity and
Externalizing Behaviors among Nonclinical Adolescents.
AB - Trait impulsivity is a risk factor for rule breaking and aggressive
(externalizing) behaviors among nonclinical youth. Buffers of trait-based risk
are of practical interest to preventing externalizing behaviors. One such buffer
may be the capacity and efforts of a child to self-regulate their physiology.
Youth who possess baseline physiological self-regulatory capacities are more
likely to maintain adaptive engagement with their environment and may be less
prone to impulsively rule break or be aggressive. Similarly, youth who are able
to use self-regulatory skills to calm their physiology in times of stress may be
less likely to externalize distress. This study examined self-regulatory capacity
and efforts as a moderator of the relationship between trait impulsivity and
externalizing behaviors, cross-sectionally and prospectively. We hypothesized
that the effect of trait impulsivity on externalizing behaviors would depend on
the presence of baseline self-regulatory capacity and/or self-regulatory efforts
during stress. Participants were 134 nonclinical adolescents (Mage = 12.59, SD =
1.20 51.9% female, 71% Caucasian). Trait impulsivity was measured using a
parental report questionnaire. Physiological self-regulatory capacity and efforts
were measured through collection of electrocardiogram data during a resting
baseline and a stressful, unsolvable anagram task, respectively. Physiological
self-regulation was quantified by calculating respiratory sinus arrhythmia scores
across baseline and stress tasks. Respiratory sinus arrhythmia is the change in
heart rate across the breathing cycle, and is hypothesized to index physiological
self-regulation capacity and efforts under specific conditions. The results
indicated that physiological self-regulation capacity, but not efforts, moderated
the effect of trait impulsivity on externalizing behaviors prospectively.
Stronger physiological self-regulatory capacity buffered the effect of greater
trait impulsivity. Implications of these findings among typically developing
youth are discussed.
PMID- 28500425
TI - Hepatic glucuronidation of 4-tert-octylphenol in humans: inter-individual
variability and responsible UDP-glucuronosyltransferase isoforms.
AB - 4-tert-Octylphenol (4-tOP) is an endocrine-disrupting chemical. It is mainly
metabolized into glucuronide by UDP-glucuronosyltransferase (UGT) enzymes in
humans. The purpose of this study was to assess inter-individual variability in
and the possible roles of UGT isoforms in hepatic 4-tOP glucuronidation in the
humans. 4-tOP glucuronidation activities in the liver microsomes and recombinant
UGTs of humans were assessed at broad substrate concentrations, and kinetics were
analyzed. Correlation analyses between 4-tOP and diclofenac or 4-hydroxybiphenyl
activities in pooled and individual human liver microsomes were also performed.
Typical CLint values were 17.8 mL/min/mg protein for the low type, 25.2 mL/min/mg
protein for the medium type, and 47.7 mL/min/mg protein for the high type. Among
the recombinant UGTs (13 isoforms) examined, UGT2B7 and UGT2B15 were the most
active of catalyzing 4-tOP glucuronidation. Although the K m values of UGT2B7 and
UGT2B15 were similar (0.36 and 0.42 uM, respectively), the CLint value of UGT2B7
(6.83 mL/min/mg protein) >UGT2B15 (2.35 mL/min/mg protein). Strong correlations
were observed between the glucuronidation activities of 4-tOP and diclofenac (a
probe for UGT2B7) or 4-hydroxybiphenyl (a probe for UGT2B15) with 0.79-0.88 of
Spearman correlation coefficient (r s) values. These findings demonstrate that 4
tOP glucuronidation in humans is mainly catalyzed by hepatic UGT2B7 and UGT2B15,
and suggest that these UGT isoforms play important and characteristic roles in
the detoxification of 4-tOP.
PMID- 28500426
TI - Identification and evaluation of potential bio-control fungal endophytes against
Ustilagonoidea virens on rice plants.
AB - False smut disease of rice is posing an increasing concern for production, not
only because of the hiking epidemic occurrence in rice production, but also
because of the challenging specific pathogenesis of the disease. The aim of this
work was to evaluate the potential of five fungal endophytes to reduce negative
effects of rice false smut fungus (Ustilagonoidea virens) on rice plants, in both
the laboratory and greenhouse. Though all the fungal isolates showed the ability
to inhibit the growth of U. virens with varying degrees, isolate E337 showed
significant antagonistic activity against the pathogenic fungi. The isolate E337
was identified as Antennariella placitae by molecular and morphological data
analysis including 18S rDNA sequence analysis. This isolate showed a significant
in vitro inhibition of mycelial growth of U. virens by dual culture method and it
was subsequently tested for its in vivo biocontrol potential on false smut
disease on rice plants. Greenhouse experiments confirmed that applications of
conidia of A. placitae protected rice plants by improving rice yield and by
decreasing the severity of false smut disease on susceptible rice plants. This is
the first report where A. placitae has been identified as a biocontrol organism.
PMID- 28500427
TI - A Japanese infant with systemic juvenile xanthogranuloma mimicking severe
microangiopathy.
PMID- 28500428
TI - A novel classification method for aid decision of traditional Chinese patent
medicines for stroke treatment.
AB - Traditional Chinese patent medicines are widely used to treat stroke because it
has good efficacy in the clinical environment. However, because of the lack of
knowledge on traditional Chinese patent medicines, many Western physicians, who
are accountable for the majority of clinical prescriptions for such medicine, are
confused with the use of traditional Chinese patent medicines. Therefore, the aid
decision method is critical and necessary to help Western physicians rationally
use traditional Chinese patent medicines. In this paper, Manifold Ranking is
employed to develop the aid-decision model of traditional Chinese patent
medicines for stroke treatment. First, 115 stroke patients from three hospitals
are recruited in the cross-sectional survey. Simultaneously, traditional Chinese
physicians determine the traditional Chinese patent medicines appropriate for
each patient. Second, particular indicators are explored to characterize the
population feature of traditional Chinese patent medicines for stroke treatment.
Moreover, these particular indicators can be easily obtained byWestern physicians
and are feasible for widespread clinical application in the future. Third, the
aid-decision model of traditional Chinese patent medicines for stroke treatment
is constructed based on Manifold Ranking. Experimental results reveal that
traditional Chinese patent medicines can be differentiated. Moreover, the
proposed model can obtain high accuracy of aid decision.
PMID- 28500429
TI - The antibiotic resistome: gene flow in environments, animals and human beings.
AB - The antibiotic resistance is natural in bacteria and predates the human use of
antibiotics. Numerous antibiotic resistance genes (ARGs) have been discovered to
confer resistance to a wide range of antibiotics. The ARGs in natural
environments are highly integrated and tightly regulated in specific bacterial
metabolic networks. However, the antibiotic selection pressure conferred by the
use of antibiotics in both human medicine and agriculture practice leads to a
significant increase of antibiotic resistance and a steady accumulation of ARGs
in bacteria. In this review, we summarized, with an emphasis on an ecological
point of view, the important research progress regarding the collective ARGs
(antibiotic resistome) in bacterial communities of natural environments, human
and animals, i.e., in the one health settings.We propose that the resistance gene
flow in nature is "from the natural environments" and "to the natural
environments"; human and animals, as intermediate recipients and disseminators,
contribute greatly to such a resistance gene "circulation."
PMID- 28500430
TI - Postnatal feeding with high-fat diet induces obesity and precocious puberty in
C57BL/6J mouse pups: a novel model of obesity and puberty.
AB - Childhood obesity and obesity-related metabolic complications are induced by a
high-fat postnatal diet. The lack of a suitable animal model, however, remains a
considerable challenge in obesity studies. In the current study, we provided high
fat diet (HFD) to dams during lactation and to pups after weaning. We also
developed a novel model of C57BL/6J mouse pups with HFD-induced postnatal
obesity. Results showed that feeding with HFD induces fat deposition and obesity
in pups. Furthermore, HFD more potently increased the body weight (BW) of male
than female pups. HFD-fed female pups were obese, underwent precocious puberty,
and showed increased kisspeptin expression in the hypothalamus. However, parental
obesity and precocious puberty exerted no synergistic effects on the HFD-induced
postnatal weight gain and puberty onset of the pups. Interestingly, some HFD-fed
litters with normal BW also exhibited precocious puberty. This finding suggested
that diet composition but not BW triggers puberty onset. Our model suggests good
construction validity of obesity and precocious puberty. Furthermore, our model
can also be used to explore the mutual interactions between diet-induced
postnatal childhood obesity and puberty.
PMID- 28500432
TI - Quality and readability of online information resources on insomnia.
AB - The internet is a major source for health information. An increasing number of
people, including patients with insomnia, search for remedies online; however,
little is known about the quality of such information. This study aimed to
evaluate the quality and readability of insomnia-related online information.
Google was used as the search engine, and the top websites on insomnia that met
the inclusion criteria were evaluated for quality and readability. The analyzed
websites belonged to nonprofit, commercial, or academic organizations and
institutions such as hospitals and universities. Insomnia-related websites
typically included definitions (85%), causes and risk factors (100%), symptoms
(95%), and treatment options (90%). Cognitive behavioral therapy for insomnia
(CBT-I) was the most commonly recommended approach for insomnia treatment, and
sleep drugs are frequently mentioned. The overall quality of the websites on
insomnia is moderate, but all the content exceeded the recommended reading ease
levels. Concerns that must be addressed to increase the quality and
trustworthiness of online health information include sharing metadata, such as
authorship, time of creation and last update, and conflicts of interest;
providing evidence for reliability; and increasing the readability for a layman
audience.
PMID- 28500433
TI - The effect of orbital radiation therapy on thyroid-associated orbitopathy
complicated with dysthyroid optic neuropathy.
AB - Thyroid-associated orbitopathy (TAO) is an inflammatory autoimmune disorder. The
most serious complication of TAO is dysthyroid optic neuropathy (DON), which can
lead to permanent vision loss because of volume expansion in the orbital apex.
Orbital radiation therapy (ORT) is an anti-inflammatory treatment used in the
treatment of active TAO. Clinical studies support radiotherapy as having a modest
effect on DON, and early radiotherapy may protect against disease progression to
DON. Current studies suggest that radiotherapy is generally safe. However, risks
still exist in some cases. The possible effects of radiotherapy on TAO,
especially complicated with DON, are reviewed. The effects of radiotherapy on DON
are not completely known, and evidence from standardized, prospective, and
multicenter clinical trials is still lacking.
PMID- 28500431
TI - Molecular aspects of MERS-CoV.
AB - Middle East respiratory syndrome coronavirus (MERS-CoV) is a betacoronavirus
which can cause acute respiratory distress in humans and is associated with a
relatively high mortality rate. Since it was first identified in a patient who
died in a Jeddah hospital in 2012, the World Health Organization has been
notified of 1735 laboratory-confirmed cases from 27 countries, including 628
deaths. Most cases have occurred in Saudi Arabia. MERS-CoVancestors may be found
in OldWorld bats of the Vespertilionidae family. After a proposed bat to camel
switching event, transmission of MERS-CoV to humans is likely to have been the
result of multiple zoonotic transfers from dromedary camels. Human-to-human
transmission appears to require close contact with infected persons, with
outbreaks mainly occurring in hospital environments. Outbreaks have been
associated with inadequate infection prevention and control implementation,
resulting in recommendations on basic and more advanced infection prevention and
control measures by the World Health Organization, and issuing of government
guidelines based on these recommendations in affected countries including Saudi
Arabia. Evolutionary changes in the virus, particularly in the viral spike
protein which mediates virus-host cell contact may potentially increase
transmission of this virus. Efforts are on-going to identify specific evidence
based therapies or vaccines. The broad-spectrum antiviral nitazoxanide has been
shown to have in vitro activity against MERS-CoV. Synthetic peptides and
candidate vaccines based on regions of the spike protein have shown promise in
rodent and non-human primate models. GLS-5300, a prophylactic DNA-plasmid vaccine
encoding S protein, is the first MERS-CoV vaccine to be tested in humans, while
monoclonal antibody, m336 has given promising results in animal models and has
potential for use in outbreak situations.
PMID- 28500434
TI - Comparing the Multicomponent Coping Power Program to Individualized Parent-Child
Treatment for Improving the Parenting Efficacy and Satisfaction of Parents of
Children with Conduct Problems.
AB - This study compared the multicomponent Coping Power (group) program to
individualized parent-child treatment with respect to changing the parenting
efficacy and satisfaction of parents of children with conduct problems. One
hundred fourteen parents of 9-12-year-old children with conduct problems were
randomized to Coping Power or individualized treatment at an urban children's
mental health clinic. Parents reported their pre- and post-treatment parenting
efficacy and parenting satisfaction (Parent Sense of Competence Scale). Mixed
effect models revealed that parenting efficacy and satisfaction significantly
increased from pre- to post-treatment, and there was no evidence that this effect
is different between Coping Power and individualized treatment, even after
controlling for initial severity of child symptomatology. Findings support the
effectiveness of Coping Power as an intervention for parenting efficacy and
satisfaction among parents of children aged 9-12 years with conduct problems.
PMID- 28500435
TI - Examining the Mechanisms of Therapeutic Change in a Cognitive-Behavioral
Intervention for Anxious Children: The Role of Interpretation Bias, Perceived
Control, and Coping Strategies.
AB - This study examined the role of theoretically meaningful mediators of therapeutic
change-interpretation bias, perceived control, and coping strategies-in a
cognitive-behavioral intervention for anxious youth. This is one of the few
studies that examined the change in potential mediator and outcome variables by
means of a longitudinal design that included four assessment points:
pretreatment, in-treatment, post-treatment, and at 4-months follow-up. Forty
seven 8- to 12-year-old children with a principal DSM-IV diagnosis of anxiety
disorder participated in the study. On each assessment point, questionnaires
assessing the mediator variables and a standardized anxiety scale were
administered to the children. The results showed that perceived control and
interpretation bias (but not coping strategies) accounted for a significant
proportion in the variability of various types of anxiety symptoms, providing a
preliminary support for the notion that these cognitive dimensions' act as
mechanisms of therapeutic change in cognitive-behavioral therapy for anxious
children.
PMID- 28500436
TI - The efficacy of a multimodal analgesia protocol in preventing heterotopic
ossification after acetabular fractures surgery.
AB - Background Heterotopic ossification (HO) after joint surgery is always a
disturbing problem for patients and surgeons. Prophylaxis is the most effective
therapy. Objective To assess the efficacy and safety of a multimodal analgesia
protocol that included parecoxib and celecoxib in preventing HO after acetabular
fracture surgery. Setting Selecting patients from trauma registry of our
hospital. Method We identified 259 patients who had acetabular fracture surgery
between January 2008 and December 2014. Hundredsixty-three patients received
parecoxib and celecoxib (Group A) and 96 patients received no prophylaxis (Group
B). The presence of HO was assessed according to the classification of Brooker et
al. at the 12 month postoperative visit. Main outcome measure The differences in
HO incidence and severity between the two groups. Results 49 patients (30.0%)
developed HO in the Group A and 44(45.8%) in Group B. The difference in total HO
incidence between the two groups was significant (P = 0.011 < 0.05, chi2 = 6.530,
OR 0.508, 95% CI (0.301-0.857). Severe HO (Brooker grade III or IV) developed in
15 patients (9.2%) in Group A and 17 patients (17.7%) in Group B. Brooker grade I
+ II was 34(20.9%) and 27(28.1%) in each group. The difference in the severity of
HO between the two Groups was significant (P = 0.008 < 0.05). Conclusion A short
term administration of parecoxib and celecoxib aids in the prevention of HO after
acetabular fractures surgery.
PMID- 28500437
TI - An evaluation of the translation of continuing education into diabetes public
health care by pharmacists.
AB - Background Pharmacists are assuming greater public health roles and partaking in
continuing education to advance knowledge and skills necessary for the provision
of this patient care. Objective We sought to determine what conditions in a
Middle East context influence how community pharmacists actually incorporate new
information into practice. Setting Community pharmacies in Qatar. Methods A
continuing professional development (CPD) program regarding the management of
fasting diabetes patients during Ramadan was developed and delivered.
Participants then maintained a record of their patient encounters when attempting
to screen fasting diabetes patients for risk and offer medication, lifestyle, and
monitoring advice. Diary entries were coded using inductive methods and follow-up
focus group discussion was conducted to further corroborate the thematic
analysis. Main outcome measure Facilitators and barriers to care. Results Forty
one pharmacists attended the CPD program and 35 subsequently made at least one
diary entry during the 3-weeks preceding and during Ramadan. One-hundred and
forty-eight submitted records and the transcript of one focus group (n = 6) were
analyzed. Three main factors were found to influence pharmacists' ability to
engage use new knowledge and skills: situational, patient, and pharmacist.
Patient reception was the overwhelming influence whereby positive interactions
encouraged pharmacists to continue screening and counseling attempts, but
difficult encounters were negative reinforcing stimuli in almost equal measure.
Conclusion In this Middle East setting, environmental factors play a considerable
role in the pharmacists' ability to engage in public health care and reinforce
that continuing education for health professionals must be closely aligned with
the realities of practice and purposefully considered as part of its evaluation.
PMID- 28500440
TI - Alternative Models to Hodgkin-Huxley Equations.
AB - The Hodgkin and Huxley equations have served as the benchmark model in
electrophysiology since 1950s. But it suffers from four major drawbacks. Firstly,
it is only phenomenological not mechanistic. Secondly, it fails to exhibit the
all-or-nothing firing mechanism for action potential generation. Thirdly, it
lacks a theory for ion channel opening and closing activation across the cell
membrane. Fourthly, it does not count for the phenomenon of voltage-gating which
is vitally important for action potential generation. In this paper, a
mathematical model for excitable membranes is constructed by introducing circuit
characteristics for ion pump exchange, ion channel activation, and voltage
gating. It is demonstrated that the model is capable of re-establishing the
Nernst resting potentials, explicitly exhibiting the all-or-nothing firing
mechanism, and most important of all, filling the long-lasting theoretical gap by
a unified theory on ion channel activation and voltage-gating. It is also
demonstrated that the new model has one half fewer parameters but fits
significantly better to experiment than the HH model does. The new model can be
considered as an alternative template for neurons and excitable membranes when
one looks for simpler models for mathematical studies and for forming large
networks with fewer parameters.
PMID- 28500439
TI - Effect of basal forebrain stimulation on extracellular acetylcholine release and
blood flow in the olfactory bulb.
AB - The olfactory bulb receives cholinergic basal forebrain input, as does the
neocortex; however, the in vivo physiological functions regarding the release of
extracellular acetylcholine and regulation of regional blood flow in the
olfactory bulb are unclear. We used in vivo microdialysis to measure the
extracellular acetylcholine levels in the olfactory bulb of urethane-anesthetized
rats. Focal chemical stimulation by microinjection of L-glutamate into the
horizontal limb of the diagonal band of Broca (HDB) in the basal forebrain, which
is the main source of cholinergic input to the olfactory bulb, increased
extracellular acetylcholine release in the ipsilateral olfactory bulb. When the
regional cerebral blood flow was measured using laser speckle contrast imaging,
the focal chemical stimulation of the HDB did not significantly alter the blood
flow in the olfactory bulb, while increases were observed in the neocortex. Our
results suggest a functional difference between the olfactory bulb and neocortex
regarding cerebral blood flow regulation through the release of acetylcholine by
cholinergic basal forebrain input.
PMID- 28500441
TI - Route simulations, compass mechanisms and long-distance migration flights in
birds.
AB - Bird migration has fascinated humans for centuries and routes crossing the globe
are now starting to be revealed by advanced tracking technology. A central
question is what compass mechanism, celestial or geomagnetic, is activated during
these long flights. Different approaches based on the geometry of flight routes
across the globe and route simulations based on predictions from compass
mechanisms with or without including the effect of winds have been used to try to
answer this question with varying results. A major focus has been use of
orthodromic (great circle) and loxodromic (rhumbline) routes using celestial
information, while geomagnetic information has been proposed for both a magnetic
loxodromic route and a magnetoclinic route. Here, we review previous results and
evaluate if one or several alternative compass mechanisms can explain migration
routes in birds. We found that most cases could be explained by magnetoclinic
routes (up to 73% of the cases), while the sun compas s could explain only 50%.
Both magnetic and geographic loxodromes could explain <25% of the routes. The
magnetoclinic route functioned across latitudes (1 degrees S-74 degrees N), while
the sun compass only worked in the high Arctic (61-69 degrees N). We discuss the
results with respect to orientation challenges and availability of orientation
cues.
PMID- 28500442
TI - Drosophila Rhodopsin 7 can partially replace the structural role of Rhodopsin 1,
but not its physiological function.
AB - Rhodopsin 7 (Rh7), a new invertebrate Rhodopsin gene, was discovered in the
genome of Drosophila melanogaster in 2000 and thought to encode for a functional
Rhodopsin protein. Indeed, Rh7 exhibits most hallmarks of the known Rhodopsins,
except for the G-protein-activating QAKK motif in the third cytoplasmic loop that
is absent in Rh7. Here, we show that Rh7 can partially substitute Rh1 in the
outer receptor cells (R1-6) for rhabdomere maintenance, but that it cannot
activate the phototransduction cascade in these cells. This speaks against a role
of Rh7 as photopigment in R1-6, but does not exclude that it works in the inner
photoreceptor cells.
PMID- 28500443
TI - Genome characterization of a novel megrivirus-related avian picornavirus from a
carnivorous wild bird, western marsh harrier (Circus aeruginosus).
AB - In this study, the complete genome of a novel picornavirus called harrier
picornavirus 1 (HaPV-1) strain harrier/MR-01/HUN/2014 (KY488458) was sequenced
and analysed from a cloacal sample of a threatened, carnivorous wild bird,
western marsh harrier (Circus aeruginosus). HaPV-1 was detectable from 2 of the 3
samples from harriers. HaPV-1 is phylogenetically related to megriviruses (genus
Megrivirus) from domestic chicken, turkey and duck, showing a similar genome
organization pattern; it also has an avian picornavirus-like "Unit A" motif in
the 3' UTR. Unlike the type-IV internal ribosomal entry site (IRES) of
megriviruses, HaPV-1 is predicted to contain a type-II-like IRES, suggesting
modular exchange of IRES elements between picornavirus genomes.
PMID- 28500444
TI - Development of a recombinase polymerase amplification assay for the diagnosis of
banana bunchy top virus in different banana cultivars.
AB - Recombinase polymerase amplification (RPA) is a rapid, isothermal amplification
method with high specificity and sensitivity. In this study, an assay was
developed and evaluated for the detection of banana bunchy top virus (BBTV) in
infected banana plants. Three oligonucleotide primer pairs were designed from the
replicase initiator protein gene sequences of BBTV to function both in RPA as
well as in polymerase chain reaction (PCR). A total of 133 symptomatic as well as
asymptomatic banana leaf samples from various cultivars were collected from the
different regions of India and evaluated for BBTV infection using the RPA assay.
BBTV was efficiently detected using crude leaf sap in RPA and the results
obtained were consistent with PCR-based detection using purified DNA as template.
To our knowledge, this is the first report of reliable diagnosis of BBTV
infection by RPA using crude leaf sap as a template.
PMID- 28500445
TI - Genetic diversity and evolutionary characteristics of type 2 porcine reproductive
and respiratory syndrome virus in southeastern China from 2009 to 2014.
AB - The objective of this study was to assess the genetic diversity of porcine
reproductive and respiratory syndrome virus circulating in Fujian province
(southeastern China). Based on 53 ORF5 nucleotide sequences collected from nine
sites, both highly pathogenic (sublineage 8.7) and lineage 1 strains were
circulating in Fujian in 2009-2014 along with lineages 3 and 5.1. Notably, the
lineage 1 strains were closely related to the NADC30 strain circulating in North
America and were the predominant strains in 2014. In addition, we found that
nonstructural protein 2 (NSP2) was the most variable nonstructural protein in
Fujian isolates, with a 36-amino-acid (aa) insertion and seven different
deletions detected in the 53 sequences examined. Similarly, analysis of GP5 amino
acid sequences showed that the isolates were highly variable in primary
neutralizing epitopes. Interesting, FJ3.2 and FJ7-2 strains have the mutation
N44K, but they exhibited high replication and high titers in MARC-145 and PAM
cells. The complete genome sequences determined for 12 type 2 isolates were 82.1
99.3% identical and were 15,016-15,407 nucleotides (nt), in length excluding the
poly(A) tail. The strains also shared 88.2-99.4% identity with strain VR2332 (the
prototype North American strain), 83.4-99.2% identity with strain JXA1 (the
prototype high-pathogenicity Chinese strain), 88.2-97.1% identity with strain CH
1a (the prototype classical Chinese strain), and 82.9-97.1% identity with strain
NADC30 (the prototype NADC30-like strain). Strikingly, phylogenetic and molecular
evolutionary analyses indicated that strain FJW05 is a spontaneous recombinant
between a circulating lineage 1 virus and the vaccine strain JXA1-R, which is
derived from the highly pathogenic strain JXA-1. Collectively, the data highlight
the epidemiology of porcine reproductive and respiratory syndrome in Fujian and
may aid in selecting a suitable vaccine for use on pig farms.
PMID- 28500446
TI - A Portuguese rapid-onset dystonia-parkinsonism case with atypical features.
PMID- 28500447
TI - [Certification guidelines and qualification courses].
AB - German regulations require a license for using ionizing radiation in medicine.
This license-called "Fachkunde"-varies for different medical procedures such as
CT, fluoroscopy, radiography, or mammography. The required frequencies and
training times also vary for different medical disciplines such as radiology,
cardiology, vascular surgery, traumatology, nuclear medicine, and radiotherapy,
among others. The quality criteria for a specific license require a minimum
training time under supervision and a minimum frequency of a wide range of
procedures. Depending on the radiation doses used and the complexity of
procedures performed, this may go up to 5000 examinations and 36 months for a
radiology resident. A refresher course is mandatory every 5 years.
PMID- 28500448
TI - Bone Loss After Denosumab: Only Partial Protection with Zoledronate.
AB - A case series of six women with postmenopausal osteoporosis who had received
continuous denosumab for 7 years and were then given a single infusion of
zoledronate (5 mg) is reported. During denosumab treatment, bone mineral density
(BMD) in the spine increased 18.5% (P = 0.006), and total hip BMD by 6.9% (P =
0.03). Post-zoledronate BMDs were measured 18-23 months after treatment, and
there were significant declines at each site (P spine = 0.043, P hip = 0.005).
Spine BMD remained significantly above the pre-denosumab baseline (+9.3%, P =
0.003), but hip BMD was not significantly different from baseline (-2.9%). At the
time of post-zoledronate BMD measurements, serum PINP levels were between 39 and
60 MUg/L (mean 52 MUg/L), suggesting that the zoledronate treatment had not
adequately inhibited bone turnover. It is concluded that this regimen of
zoledronate administration is not adequate to preserve the BMD gains that result
from long-term denosumab treatment.
PMID- 28500449
TI - Concentration polarization phenomenon in the case of mechanical pressure
difference on the membrane.
AB - We analyzed the transport of KCl solutions through the bacterial cellulose
membrane and concentration boundary layers (CBLs) near membrane with pressure
differences on the membrane. The membrane was located in horizontal-plane between
two chambers with different KCL solutions. The membrane was located in horizontal
plane between two chambers with different KCL solutions. As results from the
elaborated model, gradient of KCL concentration in CBLs is maximal at membrane
surfaces in the case when pressure difference on the membrane equals zero. The
amplitude of this maximum decreases with time of CBLs buildup. Application of
mechanical pressure gradient in the direction of gradient of osmotic pressure on
the membrane causes a shift of this maximum into the chamber with lower
concentration. In turn, application of mechanical pressure gradient directed
opposite to the gradient of osmotic pressure causes the appearance of maximum of
concentration gradient in chamber with higher concentration. Besides, the
increase of time of CBLs buildup entails a decrease of peak height and shift of
this peak further from the membrane. Similar behavior is observed for
distribution of energy dissipation in CBLs but for pressure difference on the
membrane equal to zero the maximum of energy dissipation is observed in the
chamber with lower concentration. We also measured time characteristics of
voltage in the membrane system with greater KCl concentrations over the membrane.
We can state that mechanical pressure difference on the membrane can suppress or
strengthen hydrodynamic instabilities visible as pulsations of measured voltage.
Additionally, time of appearance of voltage pulsations, its amplitude, and
frequency depend on mechanical pressure differences on the membrane and initial
quotient of KCl concentrations in chambers.
PMID- 28500450
TI - Genetic variation in matrix metalloproteinase MMP2 and MMP9 as a risk factor for
idiopathic recurrent spontaneous abortions in an Indian population.
AB - PURPOSE: Matrix metalloproteinases, MMP2 and MMP9, are found to have an important
role during ovulation and pregnancy because of their capacity to degrade
components of the extracellular matrix (ECM) thereby facilitating cell migration
and angiogenesis. In this respect, the aim of the present study was to evaluate
the association of the promoter polymorphisms -1306 C > T and -1562 C/T in MMP2
and MMP9 respectively with couples diagnosed with idiopathic recurrent
spontaneous abortions (IRSA). The expression levels of these two genes were also
studied in fetal tissue. METHODS: In this case control study, a total of 35
couples with at least three consecutive IRSA and 35 fertile couples were
included. Genotype analysis was performed using polymerase chain reaction and
Sanger sequencing. RESULTS: No statistically significant differences were found
in distribution of MMP2-1306C/T and MMP9-1562C/T genotypes in the three groups
between the cases and controls. CONCLUSION: Further genetic association studies
on a larger number of IRSA couples, as well as evaluation of more MMP
polymorphisms and their expression profiling are needed to establish the
potential role of MMP polymorphisms in IRSA.
PMID- 28500452
TI - Erythroblastopenia in a critically ill influenza patient.
PMID- 28500451
TI - Pregnancy rates for single embryo transfer (SET) of day 5 and day 6 blastocysts
after cryopreservation by vitrification and slow freeze.
AB - PURPOSE: The purpose of this study was to compare clinical and ongoing pregnancy
rates in cycles with single embryo transfer (SET) of blastocysts cryopreserved on
day 5 or day 6. Our aim was to determine whether day 6 blastocysts perform
adequately to recommend SET. METHODS: Retrospective cohort study including 468
transfer cycles for 392 women younger than age 38 undergoing SET at a university
affiliated IVF clinic in the USA. A total of 261 day 5 blastocysts and 207 day 6
blastocysts for frozen-thawed SET between 2010 and 2016 were analyzed. Data
included cryopreservation by both a slow freeze method and vitrification.
RESULTS: In total, 59.0% of day 5 SET cycles resulted in a clinical pregnancy
compared to 54.1% of day 6 blastocysts (p = 0.54). Ongoing pregnancy rates from
day 5 frozen-thawed blastocysts (51.7%) were comparable to day 6 (44.9%, p =
0.14). When looking at vitrified blastocysts only, there were no significant
differences between day 5 and day 6 blastocysts, with a clinical pregnancy rate
of 69.2% for day 5 and 72.5% for day 6 (p = 0.68). CONCLUSIONS: SETs of day 6
cryopreserved blastocysts resulted in similar clinical and ongoing pregnancy
rates compared to day 5, particularly after vitrification.
PMID- 28500453
TI - What does it mean for a critically ill patient to fare well?
PMID- 28500454
TI - Extracorporeal membrane oxygenation for poisoning in adult patients: outcomes and
predictors of mortality.
PMID- 28500457
TI - An alternative technique for greater tuberosity fractures: use of the mesh plate.
AB - INTRODUCTION: Isolated greater tuberosity (GT) fractures (AO 11-A1) tend to occur
in the younger patient population and are poorly managed by most precontoured
proximal humerus locking plates. The goal of this study was to identify and
assess an alternative treatment strategy for greater tuberosity fractures.
MATERIALS AND METHODS: A retrospective review of all cases of isolated greater
tuberosity fractures treated with a 2.4/2.7 mesh plate (Synthes) between 2010 and
2015 was conducted. Patient demographics, operative reports, and clinical notes
were reviewed. The time to radiographic union was assessed. Clinical outcomes
were retrieved from patients at their follow-up visits or via mailed Disabilities
of the Arm, Shoulder, Hand (DASH) questionnaires. RESULTS: Ten patients with
isolated GT fractures treated with mesh plating were identified with an average
age of 47.1 years. The average radiographic follow-up was 7.2 months and the
average clinical follow-up was 8.0 months. The mean time to union was 8.5 weeks.
Two patients underwent elective hardware removal. The mean DASH at final follow
up was 28.2 (+/-22.4), while the mean DASH work was 13.6 (+/-19.1). CONCLUSION:
We have identified a viable alternative treatment option for the surgical
management of isolated greater tuberosity fractures using a mesh plate that can
be contoured to the patient's anatomy. Surgeons should be aware of this option
for select patients.
PMID- 28500456
TI - Sex differences in spatial accuracy relate to the neural activation of
antagonistic muscles in young adults.
AB - Sex is an important physiological variable of behavior, but its effect on motor
control remains poorly understood. Some evidence suggests that women exhibit
greater variability during constant contractions and poorer accuracy during goal
directed tasks. However, it remains unclear whether motor output variability or
altered muscle activation impairs accuracy in women. Here, we examine sex
differences in endpoint accuracy during ankle goal-directed movements and the
activity of the antagonistic muscles. Ten women (23.1 +/- 5.1 years) and 10 men
(23 +/- 3.7 years) aimed to match a target (9 degrees in 180 ms) with ankle
dorsiflexion. Participants performed 50 trials and we recorded the endpoint
accuracy and the electromyographic (EMG) activity of the primary agonist
(Tibialis Anterior; TA) and antagonist (Soleus; SOL) muscles. Women exhibited
greater spatial inaccuracy (Position error: t = -2.65, P = 0.016) but not
temporal inaccuracy relative to men. The motor output variability was similar for
the two sexes (P > 0.2). The spatial inaccuracy in women was related to greater
variability in the coordination of the antagonistic muscles (R 2 0.19, P = 0.03).
These findings suggest that women are spatially less accurate than men during
fast goal-directed movements likely due to an altered activation of the
antagonistic muscles.
PMID- 28500455
TI - The intensive care medicine research agenda on septic shock.
AB - Septic shock remains a global health challenge with millions of cases every year,
high rates of mortality and morbidity, impaired quality of life among survivors
and relatives, and high resource use both in developed and developing nations.
Care and outcomes are improving through organisational initiatives and updated
clinical practice guidelines based on clinical research mainly carried out by
large collaborative networks. This progress is likely to continue through the
collaborative work of the established and merging trials groups in many parts of
the world and through refined trial methodology and translational work. In this
review, international experts summarize the current position of clinical research
in septic shock and propose a research agenda to advance this field.
PMID- 28500458
TI - Occurrence of Vascular Lake Phenomenon as a Predictor of Improved Tumor Response
in HCC Patients That Underwent DEB-TACE.
AB - PURPOSE: To evaluate incidence and predictive factors for the vascular lake
phenomenon (VLP), as well as to compare local and overall tumor response in
patients with and without VLP induced during DEB-TACE for HCC. METHODS: A total
of 200 consecutive patients with 323 HCC nodules underwent first-session DEB-TACE
from 2011 to 2014. Patients were divided in two groups, according to the presence
of the VLP during DEB-TACE. Pre- and post-treatment imaging studies (CT or MRI)
were performed. Primary endpoint was assessment of tumor response, evaluated by
mRECIST. Comparison of response rates between the VLP group and the non-VLP group
was performed. Secondary endpoints were the determination of incidence rate and
predictive factors for the VLP. RESULTS: The VLP was observed in 39/323 (12.1%)
of the nodules treated. At multivariate logistic regression analysis, tumor size
>=3 cm in diameter (OR 13.95; 95% CI 3.60-54.05), presence of a pseudocapsule (OR
6.67; 95% CI 1.45-30.59) and alpha-fetoprotein levels (OR 1.004; 95% CI 1.000
1.007) remained predictive for the VLP occurrence. On a nodule-based analysis (p
< 0.001), target lesion response analysis (p = 0.003) and overall response
analysis (p = 0.004) the VLP group presented a higher objective response rate
than the non-VLP group. CONCLUSION: VLP is observed in 12% of the patients and
happens more frequently in large and encapsulated tumors. It seems to be
associated with better local and overall responses in HCC patients who underwent
DEB-TACE.
PMID- 28500459
TI - Personalized Feedback on Staff Dose in Fluoroscopy-Guided Interventions: A New
Era in Radiation Dose Monitoring.
AB - PURPOSE: Radiation safety and protection are a key component of fluoroscopy
guided interventions. We hypothesize that providing weekly personal dose feedback
will increase radiation awareness and ultimately will lead to optimized behavior.
Therefore, we designed and implemented a personalized feedback of procedure and
personal doses for medical staff involved in fluoroscopy-guided interventions.
MATERIALS AND METHODS: Medical staff (physicians and technicians, n = 27)
involved in fluoroscopy-guided interventions were equipped with electronic
personal dose meters (PDMs). Procedure dose data including the dose area product
and effective doses from PDMs were prospectively monitored for each consecutive
procedure over an 8-month period (n = 1082). A personalized feedback form was
designed displaying for each staff individually the personal dose per procedure,
as well as relative and cumulative doses. This study consisted of two phases: (1)
1-5th months: Staff did not receive feedback (n = 701) and (2) 6-8th months:
Staff received weekly individual dose feedback (n = 381). An anonymous evaluation
was performed on the feedback and occupational dose. RESULTS: Personalized
feedback was scored valuable by 76% of the staff and increased radiation dose
awareness for 71%. 57 and 52% reported an increased feeling of occupational
safety and changing their behavior because of personalized feedback,
respectively. For technicians, the normalized dose was significantly lower in the
feedback phase compared to the prefeedback phase: [median (IQR) normalized dose
(phase 1) 0.12 (0.04-0.50) uSv/Gy cm2 versus (phase 2) 0.08 (0.02-0.24) uSv/Gy
cm2, p = 0.002]. CONCLUSION: Personalized dose feedback increases radiation
awareness and safety and can be provided to staff involved in fluoroscopy-guided
interventions.
PMID- 28500460
TI - Prophylactic Temporary Occlusion of the Cystic Artery Using a Fibered Detachable
Coil During 90Y Radioembolization.
AB - PURPOSE: To address the feasibility of prophylactic temporary occlusion of the
cystic artery using a detachable coil during 90Y radioembolization. MATERIALS AND
METHODS: From January 2012 to October 2016, nine patients underwent temporary
occlusion of the cystic artery during 90Y radioembolization. Based on the
planning hepatic angiography, a detachable coil was deployed into the cystic
artery, which arose from a more distal level (e.g., right anterior hepatic
artery) than its usual origin, but the proximal 1 cm was left inside the
microcatheter. 90Y microspheres were infused proximal to the cystic artery where
the 99mTc-MAA had been infused, and then the coil was retrieved. Afterward, the
patients underwent PET/CT imaging. Medical records were reviewed, and the
differences in the uptake of 99mTc-MAA and 90Y microspheres in the gallbladder
were evaluated using Wilcoxon's signed-rank test. RESULTS: Temporary placement of
a detachable coil was feasible in all cases. On the angiograms obtained after
detachable coil placement, the distal cystic artery and gallbladder were
partially identifiable in eight of the nine (88.8%) patients, but fully restored
after the removal of the coils in all cases. The proportional uptake of 99mTc-MAA
(mean, 4.35%) and 90Y (mean, 0.90%) in the gallbladder was significantly
different due to the temporary occlusion of the cystic artery (p = 0.004). No
clinical complications were identified for three months after the procedure.
CONCLUSION: Temporary occlusion of the cystic artery using a detachable coil
appeared to be feasible and effective in reducing 90Y uptake in the gallbladder.
PMID- 28500461
TI - Predicting Success in Percutaneous Transhepatic Biliary Drainage.
AB - PURPOSE: To develop a model to predict successful bilirubin decrease following
percutaneous biliary drain placement. METHODS: A total of 257 patients who were
identified having undergone percutaneous transhepatic biliary drain placement
(PTBD) at our institution between 2002 and 2013 had their medical records and
imaging reviewed. Of those, 190 of these patients met criteria and were used in
the analysis. A regression model was performed on logarithm-transformed collected
variables to predict post-drainage logarithmic transformed total bilirubin
levels. A stepwise variable selection method based on Schwarz Bayesian
Information Criterion was used to select the most closely associated variables.
The model was validated with a Monte Carlo simulation. A short program was
developed to calculate the point estimate using the model developed and compared
to actual values. RESULTS: The variables that best predicted bilirubin reduction
were initial Tbl (PrTbl), INR and ALT. The selected model had a root mean squared
error of 0.8. The model had a negative predictive value (PoTbl is below 2 mg/dL)
of 83%. CONCLUSIONS: PTBD may not achieve decreasing bilirubin in patients with a
malignant obstruction. This is an initial model that can help determine which
patients may not benefit from PTBD placement. With more patients, the model's
validity can be increased and provide useful clinical determinant to aide patient
care.
PMID- 28500462
TI - Perfusion index and left ventricular output correlation in healthy term infants.
AB - : Perfusion index (PI) is a non-invasive marker of peripheral perfusion which is
detected by an oximeter. We aimed to assess the correlation between PI and left
ventricular output (LVO) in healthy term infants at the time of the screening for
congenital heart disease (CHD). PI was measured at 48+/-2 h of life in the
infant's right hand (PIrh) and in one foot (PIf) contemporary to SpO2 for CHD
screening. Heart ultrasound was performed immediately after the screening
procedure for measuring LVO. Forty-nine healthy term infants were studied. PIrh
and PIf were 1.9 +/- 0.6 and 1.9 +/- 0.8, respectively, and their values were
significantly correlated (p < 0.0001) with a coefficient r = 0.8. Bland-Altman
analysis shows a mean difference of -0.06 +/- 0.47 (95%LOA -0.98-0.86). PIrh
correlates with LVO (r = 0.68) and LVO/kg (r = 0.61) with an increase of 151
mL/min (95%CI 103-198) of LVO and 42 mL/kg/min (95%CI 26-58) of LVO/kg per point
of PIrh. PIf correlates with LVO (r = 0.74) and LVO/kg (r = 0.73) with an
increase of 123 mL/min (95%CI 90-155) of LVO and 37 mL/kg/min (95%CI 27-47) of
LVO/kg per point of PIf. CONCLUSION: PI is significantly correlated with LVO in
healthy term infants. These results support the theoretical potential role of PI
in the CHD screening. What is Known: * Perfusion index is an indirect measure of
perfusion which depends on cardiac output and peripheral vascular resistance
whose normal values have been documented in term and preterm infants in the first
days of life. * Perfusion index has been proposed for the screening of congenital
heart disease with duct-dependent systemic circulation in term infants. What is
New: * Perfusion index shows a significant correlation with the left ventricular
output in term infants at the moment of the screening for congenital heart
disease. * Perfusion index might have a theoretical role in improving the
accuracy of pulse oximetry in the screening of CHD associated to low systemic
flow.
PMID- 28500463
TI - Comparison of four different intraosseous access devices during simulated
pediatric resuscitation. A randomized crossover manikin trial.
AB - : The aim of the study was to compare the success rate, procedure time, and user
satisfaction of pediatric NIOTM compared to Pediatric BIG(r), EZ-IO(r), and
Jamshidi intraosseous access devices. This was a randomized, crossover manikin
trial with 87 paramedics. The correct location of intraosseous access when using
NIO, BIG, EZ-IO, and Jamshidi was varied and was respectively 100, 90, 90, and
90%. The time required to obtain intravascular access (time T1) in the case of
NIO, BIG, EZ-IO, and Jamshidi was varied and amounted to 9 s [IQR, 8-12] for NIO,
12 s [IQR, 9-16] for BIG, 13.5 s [IQR, 11-17] for the EZ-IO, and 15 s [IQR, 13
19] for Jamshidi. The paramedics evaluated each device on the subjective ease
with which they performed the procedures. The intraosseous device, which proved
the easiest to use was NIO, which in the case of CPR received a median rating of
1.5 (IQR, 0.5-1.5) points. CONCLUSION: Our study found that NIO(r) is superior to
BIG(r), EZ-IO(r), and Jamshidi. NIO(r) achieved the highest first attempt success
rate. NIO(r) also required the least time to insert and easiest to operate even
by novice users. Further study is needed to test our findings in cadavers or
human subjects. Based on our findings, NIO(r) is a promising intraosseous device
for use in pediatric resuscitation. What is Known: * Venous access in acutely ill
pediatric patients, such as those undergoing cardiopulmonary resuscitation, is
needed for prompt administration of drugs and fluids. * Intraosseous access is
recommended by American Heart Association and European Resuscitation council if
vascular access is not readily obtainable to prevent delay in treatment. What is
New: * This simulated pediatric resuscitation compared performance of four
commercially available pediatric intraosseous devices in a manikin model. *
NIO(r) outperformed BIG(r), EZ-IO(r), and Jamshidi in first attempt success rates
and time of procedure among novice users.
PMID- 28500465
TI - The Information Sharing Statement Grows Some Teeth.
PMID- 28500466
TI - A three-dimensional pelvic model made with a three-dimensional printer:
applications for laparoscopic surgery to treat rectal cancer.
AB - To help understand the three-dimensional (3D) spatial relationships among the
highly complex structures of the pelvis, we made a novel 3D pelvic model with a
3D printing system. We created two pelvic models including the muscles, vessels,
nerves, and urogenital organs; the first based on the pelvic anatomy of a healthy
male volunteer and the second on the pelvic anatomy of a female volunteer with
rectal cancer. The models clearly demonstrated the complicated spatial
relationships between anatomical structures in the pelvis. Surgeons could use
these models to improve their spatial understanding of pelvic anatomy, which
could consequently improve the safety and efficiency of laparoscopic rectal
cancer surgery.
PMID- 28500464
TI - Global skin colour prediction from DNA.
AB - Human skin colour is highly heritable and externally visible with relevance in
medical, forensic, and anthropological genetics. Although eye and hair colour can
already be predicted with high accuracies from small sets of carefully selected
DNA markers, knowledge about the genetic predictability of skin colour is
limited. Here, we investigate the skin colour predictive value of 77 single
nucleotide polymorphisms (SNPs) from 37 genetic loci previously associated with
human pigmentation using 2025 individuals from 31 global populations. We
identified a minimal set of 36 highly informative skin colour predictive SNPs and
developed a statistical prediction model capable of skin colour prediction on a
global scale. Average cross-validated prediction accuracies expressed as area
under the receiver-operating characteristic curve (AUC) +/- standard deviation
were 0.97 +/- 0.02 for Light, 0.83 +/- 0.11 for Dark, and 0.96 +/- 0.03 for Dark
Black. When using a 5-category, this resulted in 0.74 +/- 0.05 for Very Pale,
0.72 +/- 0.03 for Pale, 0.73 +/- 0.03 for Intermediate, 0.87+/-0.1 for Dark, and
0.97 +/- 0.03 for Dark-Black. A comparative analysis in 194 independent samples
from 17 populations demonstrated that our model outperformed a previously
proposed 10-SNP-classifier approach with AUCs rising from 0.79 to 0.82 for White,
comparable at the intermediate level of 0.63 and 0.62, respectively, and a large
increase from 0.64 to 0.92 for Black. Overall, this study demonstrates that the
chosen DNA markers and prediction model, particularly the 5-category level; allow
skin colour predictions within and between continental regions for the first
time, which will serve as a valuable resource for future applications in forensic
and anthropologic genetics.
PMID- 28500467
TI - Psoriasis in children with type 1 diabetes: A new comorbidity to be considered?
PMID- 28500468
TI - Rickettsia spp. in Dermacentor marginatus ticks: analysis of the host-vector
pathogen interactions in a northern Mediterranean area.
AB - In this work, we have analyzed the key features of Rickettsia spp. maintenance in
Dermacentor marginatus ticks in four regions of the northern Mediterranean area,
where extensive investigations are currently lacking. For this purpose, 380 adult
D. marginatus ticks were collected from vegetation and wild ungulates during a 3
year study. A host-vector-pathogen interaction approach was applied to
investigate the key components of the disease systems and evaluate their
respective weight in the intensity of infection in natural foci. A high
variability in the R. slovaca infection rate among sampling sites was observed,
whereas R. raoultii was sporadically present and at low infection rates.
Dermacentor marginatus presence was confirmed in all the investigated regions.
The local wild boar population showed a strong association with adult D.
marginatus ticks. The results of this investigation suggest that wild boars not
only maintain D. marginatus populations by feeding adult ticks, but may also have
a potential role in the eco-epidemiology of rickettsioses, as carriers of
rickettsiae-infected ticks. The public health implications of these results are
discussed.
PMID- 28500469
TI - Aggression Predicts Changes in Peer Victimization that Vary by Form and Function.
AB - Peer victimization is predictive of serious problems in adjustment, especially
among children who are both victimized and aggressive. This study investigated
how different types of aggression contribute to later victimization.
Specifically, we examined prospective relationships between the types of
aggression that children perpetrated and the types that they experienced at the
hands of others. Trained observers coded schoolyard behavior of 553 children in
grades 3-6 during the initial year of a bullying intervention program. Both
observed aggression and victimization were specified by form (direct, indirect)
and function (proactive, reactive). Total hourly rates of victimization were
highest in the upper grades. Direct-reactive aggression uniquely predicted
increases in victimization, while direct-proactive aggression predicted
decreases, particularly in direct-proactive victimization. Indirect-proactive
aggression (e.g., derogatory gossip) predicted increases in indirect-proactive
victimization only in the control group. Indirect-reactive aggression and
victimization occurred too rarely to detect change. Aggression-victimization
relationships did not differ for boys and girls. Discussion considers why
children might risk direct reactive aggression in the face of increased
victimization. Different sequelae for different forms and functions of aggression
highlight the need to resolve theoretical ambiguities in defining proactive and
reactive aggression.
PMID- 28500470
TI - Neural Correlates of Emotion Reactivity and Regulation in Young Children with
ADHD Symptoms.
AB - Emotion reactivity and regulation are frequently impaired in individuals with
attention-deficit/hyperactivity disorder (ADHD), yet few studies have examined
these factors in young children with ADHD, and none have explored the neural
correlates of emotion reactivity and regulation in this group through event
related potentials (ERPs). Children aged 4 to 7 with (n = 25; 18 boys) and
without (n = 29; 20 boys) ADHD symptoms completed an attention task composed of
four blocks: baseline, frustration, suppression, and recovery. In the frustration
and suppression blocks, negative affect was induced by false negative feedback.
During the suppression block, children were asked to suppress emotional
expressions. Neural reactivity, assessed via the N2 and P3 components, suggests
that children with ADHD symptoms processed the emotional induction differently
than typically developing (TD) children. TD children demonstrated decreased N2
and increased P3 amplitudes at frontal and frontocentral regions across task
conditions whereas children with ADHD symptoms showed relatively stable N2 and P3
amplitudes. This pattern suggests that young children with ADHD symptoms are not
as effective as their TD peers in modulating attention allocation and cognitive
control in emotionally laden situations. The present study underscores that
emotional contexts may exacerbate attentional control deficits in young children
with ADHD symptoms.
PMID- 28500471
TI - W-enriched satellite sequence in the Indian meal moth, Plodia interpunctella
(Lepidoptera, Pyralidae).
AB - The W chromosome of most lepidopteran species represents the largest
heterochromatin entity in the female genome. Although satellite DNA is a typical
component of constitutive heterochromatin, there are only a few known satellite
DNAs (satDNAs) located on the W chromosome in moths and butterflies. In this
study, we isolated and characterized new satDNA (PiSAT1) from microdissected W
chromosomes of the Indian meal moth, Plodia interpunctella. Even though the
PiSAT1 is mainly localized near the female-specific segment of the W chromosome,
short arrays of this satDNA also occur on autosomes and/or the Z chromosome.
Probably due to the predominant location in the non-recombining part of the
genome, PiSAT1 exhibits a relatively large nucleotide variability in its
monomers. However, at least a part of all predicted functional motifs is located
in conserved regions. Moreover, we detected polyadenylated transcripts of PiSAT1
in all developmental stages and in both sexes (female and male larvae, pupae and
adults). Our results suggest a potential structural and functional role of PiSAT1
in the P. interpunctella genome, which is consistent with accumulating evidence
for the important role of satDNAs in eukaryotic genomes.
PMID- 28500473
TI - Orchid Bee (Apidae: Euglossini) Communities in Atlantic Forest Remnants and
Restored Areas in Parana State, Brazil.
AB - In this study, we compare orchid bee communities surveyed in four forest remnants
of the Atlantic Forest and four reforested areas characterized by seasonal semi
deciduous forest vegetation in different successional stages (mature and
secondary vegetation), located in southern Brazil. The sizes of forest remnants
and reforested areas varied from 32.1 to 583.9 ha and from 11.3 to 33.3 ha,
respectively. All reforested areas were located near one forest remnant. During
samplings, totaling nine per study area, euglossine males were attracted to eight
scent baits and captured with bait trap and entomological nets. Each forest
remnant and its respective reforested area were sampled simultaneously by two
collectors. We collected 435 males belonging to nine species of orchid bees
distributed in four genera. The number of individuals and species did not differ
significantly between different areas, except for a reforested area (size 33.3
ha), which was located far from its respective forest remnant. Our findings also
revealed an apparent association between an orchid bee species (Euglossa
annectans Dressler 1982) and the most preserved area surveyed in our study,
suggesting that this bee is a potential indicator of good habitat quality in
recuperating or preserved areas. Our results suggest that reforested habitats
located near forest remnants have a higher probability of having reinstated their
euglossine communities.
PMID- 28500472
TI - Impaired Interpretation of Others' Behavior is Associated with Difficulties in
Recognizing Pragmatic Language in Patients with Schizophrenia.
AB - Much attention has been paid to the pragmatic language function in schizophrenia.
This study of Japanese patients with schizophrenia examined the relationship
between impaired interpretation of the behaviors of other people in social
contexts and the ability to recognize metaphor and irony. We assessed 34 patients
with schizophrenia and 34 normal subjects using first- and second-order theory of
mind tasks, the Metaphor and Sarcasm Scenario Test, and the Dewey Story Test
(which tests the ability to judge others' social behaviors). We compared the
performance between the groups and analyzed correlations between the tasks. All
tasks revealed significant deficits in the patients compared with the controls.
In the patient group, metaphor comprehension was correlated with the ability to
judge normal behaviors, and irony comprehension was correlated with the ability
to judge abnormal behaviors, suggesting that deficits of social cognition in
schizophrenia include these two types of factors associated with pragmatic
language.
PMID- 28500475
TI - Mitteilungen der DGKFO.
PMID- 28500474
TI - Comparisons of hospital output in Canada: national and international
perspectives.
AB - Current cost-based approach in measuring health care output does not allow
decomposition of health care expenditure into price and output components. In
this paper we propose an episode-based direction measurement method which closely
resembles the concept of output in the system of national accounts. Using data
from the Canadian Institute for Health Information, we calculate a quality
unadjusted output index of the Canadian hospital sector for the periods 1996
2005. The result shows that total output increases at an average annual growth
rate of 1.49%. We expect that with the quality adjustment the actual rate is
higher. This is in contrast with the long-held assumption that health care
productivity growth is zero. Our results provide key information on the ongoing
health care policy debate.
PMID- 28500477
TI - Impact of a Program for the Management of Aggressive Behaviors on Seclusion and
Restraint Use in Two High-Risk Units of a Mental Health Institute.
AB - The Omega Program for the Management of Aggressive Behaviors aims to reduce
patients' dangerous behaviors, towards themselves or others, and to reduce the
use of seclusion and restraint (S/R). A previous study in a Mental Health
Institute (Montreal, Canada) showed that implementing this program allowed
employees of the intensive care and emergency units to gain confidence in coping
with patients' aggressions and to reduce their psychological distress. The
present study, conducted in the same high-risk units, assesses the effect of the
program on S/R use. We hypothesize that the incidence and duration of S/R should
diminish significantly following the implementation of the program in both units.
This naturalistic, prospective study covered archival data between April 2010 and
July 2014. Pre-training data (April 2010-December 2011) were compared to data
during training (January 2012-October 2012) and to post-training data (November
2012-July 2014) for both units. In the intensive care unit, we confirmed an
increase of both mean daily number and duration of S/R by admissions in pre
training, followed by a decrease during the training and post-training. In the
emergency unit, a decreasing trend is seen during the entire period thus
suggesting that the decrease in S/R may be independent of the training. These
findings suggest that Omega is a promising intervention program to use in an
intensive care unit. However, a more global approach, including institutional
changes in culture and attitude, can be important factors to develop to increase
the positive outcomes.
PMID- 28500476
TI - Update on APOA5 Genetics: Toward a Better Understanding of Its Physiological
Impact.
AB - PURPOSE OF REVIEW: This review is intended to summarize the genetic studies
published during the last 3 years that help us understand the physiology of apoAV
and its clinical implications. RECENT FINDINGS: APOA5 is probably the gene with
the strongest effect on triglyceride (TG) metabolism. APOA5 is almost exclusively
expressed in the liver, and its product apoAV has a very low circulating
concentration. New physiological roles of apoAV have been recently elucidated,
such as control of chylomicron production in the intestine and TG accumulation in
adipose tissue. The key role of APOA5 in TG metabolism has been largely shown
through genetic studies in association with either severe or moderate
hypertriglyceridemia. Studies suggest that APOA5 variants affect not only total
TG concentrations but also the entire lipoprotein subclass distribution, shifting
them toward atherogenic dyslipidemia in high-risk subjects. Environmental
interactions and epigenetic factors are also crucial in regulating these
processes. Delineation of the mechanisms involved in the transcriptional control
of the gene, combined with determination of biological significance of the SNPs
in the APOA5 locus, would help to fully understand the effect of APOA5 on TGs. In
summary, APOA5 variants cause hypertriglyceridemia. In high cardiovascular risk
patients (e.g., patients with metabolic syndrome or type 2 diabetes), APOA5
variants elevate TG levels and shift the entire lipoprotein subclass distribution
toward atherogenic dyslipidemia. At a physiological level, apoAV seems to
encompass more roles than those initially suggested after its discovery.
PMID- 28500478
TI - Effect of stenosis eccentricity on the functionality of coronary bifurcation
lesions-a numerical study.
AB - Interventional cardiologists still rely heavily on angiography for the evaluation
of coronary lesion severity, despite its poor correlation with the presence of
ischemia. In order to improve the accuracy of the current diagnostic procedures,
an understanding of the relative influence of geometric characteristics on the
induction of ischemia is required. This idea is especially important for coronary
bifurcation lesions (CBLs), whose treatment is complex and is associated with
high rates of peri- and post-procedural clinical events. Overall, it is unclear
which geometric and morphological parameters of CBLs influence the onset of
ischemia. More specifically, the effect of stenosis eccentricity is unknown.
Computational fluid dynamic simulations, under a geometric multiscale framework,
were executed for seven CBL configurations within the left main coronary artery
bifurcation. Both concentric and eccentric stenosis profiles of mild to severe
constriction were considered. By using a geometric multiscale framework, the
fractional flow reserve, which is the gold-standard clinical diagnostic index,
could be calculated and was compared between the eccentric and concentric
profiles for each case. The results suggested that for configurations where the
supplying vessel is stenosed, eccentricity could have a notable effect on and
therefore be an important factor that influences configuration functionality.
PMID- 28500479
TI - [Catheter ablation of persistent atrial fibrillation : Where do we go?]
AB - Despite the very promising initial results of clinical studies, catheter ablation
of persistent atrial fibrillation (AF) remains a challenge in modern
electrophysiology. On the basis of the hypothesized pathophysiological
mechanisms, a variety of ablation strategies have been developed over the course
of time. The current ablation strategies range from pulmonary vein isolation
(PVI) alone as first-line therapy, through ablation of multiple linear lesions,
ablation of complex fractionated atrial electrograms (CFAE), rotor ablation,
isolation of fibrotic and scar tissue up to isolation of the left atrial
appendage (LAA); however, it is unclear even to the present day whether these
complex and time-consuming strategies actually improve the success rate of
ablation therapy. In recent years it has reproducibly been shown that with these
ablation techniques more than one procedure is often necessary in order to
achieve a stable sinus rhythm and even then only limited satisfactory success
rates can be expected. The only currently established ablation endpoint is PVI.
The stringent treatment of risk factors, such as arterial hypertension and
obesity is becoming a focus of interest as an additive concept to ablation.
PMID- 28500480
TI - [Pulmonary vein isolation for atrial fibrillation : Findings from long-term
follow-up].
AB - Atrial fibrillation is by far the most common cardiac arrhythmia in humans. The
incidence of atrial fibrillation increases with age and will increase even more
in the future due to the demographic changes in the population. Therefore, this
arrhythmia will have a growing clinical and socioeconomic impact. Although there
are established pharmaceutical treatment options, atrial fibrillation is one of
the major causes of stroke, heart failure and cardiovascular morbidity and
mortality. The latest guidelines recommend the invasive procedure of
circumferential pulmonary vein isolation (PVI) as an effective treatment of
paroxysmal and persistent atrial fibrillation. This article summarizes the
current long-term follow-up data after PVI.
PMID- 28500482
TI - Improved Yield of High Molecular Weight Hyaluronic Acid Production in a Stable
Strain of Streptococcus zooepidemicus via the Elimination of the Hyaluronidase
Encoding Gene.
AB - Despite the significant potential of Streptococcus zooepidemicus for hyaluronic
acid (HA) production with high molecular weight (MW), the HA degrading properties
of hyaluronidase prevents the bacteria to achieve enhanced HA yield with high MW.
In the present study, we aim to knockout the hyaluronidase enzyme and assess its
effects on the yield and MW of the produced HA. The kanamycin resistance gene
between the left and right arms of hyaluronidase gene was inserted into pUC18
plasmid to construct pUC18-L-kanar-R as a recombinant suicide plasmid. The
construct was then transferred into S. zooepidemicus to induce the homologous
recombination between the hyaluronidase gene and the kanamycin resistance gene.
Gene deletion was confirmed by PCR and enzyme assay. The product was cultured on
selectable medium in which the MW of HA was increased from 1.5 to 3.8 MDa. The
yield of HA production using the mutant strain was higher in all different
concentrations of glucose from 40 to 120 g/l. Moreover, glucose increase results
in higher HA production within both wild-type and recombinant strains. However,
the growth rate of HA concentration (the slope of the plot), as a consequence of
increased glucose concentration, is always higher for the recombinant strain.
Unlike the wild-type strain, there was no sharp HA production drop approaching
the 6 g/l HA concentration. In conclusion, hyaluronidase activity and HA
concentration and MW exhibited a mutual control on each other. Based on our
results, deletion of the hyaluronidase gene positively affects the yield and MW
of HA.
PMID- 28500483
TI - The effect of repetitive flexion and extension fatigue loading on the young
porcine lumbar spine, a feasibility study of MRI and histological analyses.
AB - BACKGROUND: The biomechanical mechanisms of failure of FSUs have been studied but
the correlation of repetitive flexion and extension loadings to the initial phase
of fatigue in young FSUs are still not known. The purpose of the study was to
examine the fatigue results of low magnitude repetitive flexion and extension
loading on porcine lumbar Functional Spinal Units (FSUs) with Magnetic Resonance
Imaging (MRI) and histology. METHODS: Eight FSUs were subject to repetitive pivot
flexion and eight to extension loading by a protocol of 20 000 cycles at 1 Hz
with a load of 700 N. All loaded FSUs (N = 16) were examined with MRI and
histology post loading. Three FSUs were examined with MRI as controls. Further
three FSUs were non loaded histology controls. RESULTS: Fifteen (94%) of the
loaded FSUs have decreased MRI signal in the growth zone of the superior vertebra
and 12 (75%) in the inferior vertebrae. Fourteen (88%) FSUs have increased signal
in the superior vertebral body. Fourteen (88%) FSUs have a reduced signal in all
or any endplate. The histology morphometry displayed that the unstained parts of
the epiphyseal growth zone were larger among the loaded FSUs (mean 29% vs 4%) and
that the chondrocytes in the endplate and growth zones had abnormal structure and
deformed extracellular matrix. CONCLUSION: Repetitive loading of young porcine
FSUs in both extension and flexion causes concurrent MRI and histological changes
in the growth zones and endplates, which could be a first sign of fatigue and an
explanation for the disc, apophyseal and growth zone injuries seen among
adolescent athletes.
PMID- 28500481
TI - Pathways Linking Adverse Childhood Experiences to Cigarette Smoking Among Young
Black Men: a Prospective Analysis of the Role of Sleep Problems and Delayed
Reward Discounting.
AB - BACKGROUND: African American men experience increases in smoking during the young
adult transition. Exposure to childhood adversity, a risk factor which
disproportionately affects African American men, has been identified as a robust
precursor to health risk behavior in general and cigarette smoking in particular.
The intermediate mechanisms that transmit the influence of early adversity to
smoking behavior are not well understood. PURPOSE: We tested a model of the
escalation of smoking behaviors among young adult African American men,
investigating sleep disturbance and delayed reward discounting as intermediate
factors linking adverse childhood experiences with smoking. METHODS: Hypotheses
were tested with three waves of data (M age-T1 = 20.34, M age-T2 = 21.92, M age
T3 = 23.02) from 505 African American men living in rural counties in South
Georgia. Men provided self-report data on their adverse childhood experiences,
sleep problems, and smoking behavior using audio-assisted computer self
interviews. Men also completed a computer-based delayed reward discounting task.
RESULTS: Structural equation modeling analyses supported our hypotheses: Adverse
childhood experiences predicted poor sleep adequacy, which forecast increases in
delayed reward discounting; discounting, in turn, predicted increased smoking.
Significant indirect pathways were detected linking adversity to discounting via
sleep adequacy and linking sleep adequacy to smoking via discounting.
CONCLUSIONS: Prevention and intervention researchers can draw on these findings
to develop programs that focus on sleep adequacy to reduce smoking in African
American men exposed to childhood adversity.
PMID- 28500484
TI - Association of folate metabolism gene polymorphisms and haplotype combination
with pulmonary embolism risk in Chinese Han population.
AB - In this study, we aimed to investigate the association of four single nucleotide
polymorphisms (SNPs) (MTHFR 677 C > T, MTHFR 1298 A > C, MTR 2756 A > G and MTRR
66 A > G), gene-gene interaction and haplotype combination with pulmonary
embolism (PE) risk based on Chinese Han population. Logistic regression was
performed to investigate association between four SNPs within folate metabolism
gene and PE risk, and GMDR model was used to investigate the additional gene-gene
interactions among the four SNPs. Logistic analysis showed that rs1801133 and
rs1801131 in MTHFR gene were associated with increased PE risk in both additive
and dominant models. The carriers with homozygous mutant of rs1801133
polymorphism and homozygous of rs1801131 were associated with increased PE risk,
and ORs (95% CI) were 1.71(1.24-2.21) and 1.58 (1.24-2.01), respectively. We also
found a significant gene-gene interaction between rs1801133 and rs1801131 on PE.
Overall, the cross-validation consistency of this two-locus model was 10/10, and
the testing accuracy was 60.72%, after adjusting for covariates. Haplotype
containing the rs1801133- T and rs1801131- C alleles were associated with a
statistically increased PE risk, OR (95% CI) = 2.68 (1.28-4.13), P < 0.001. We
found that rs1801133 and rs1801131 within MTHFR gene, their interaction, and
haplotype containing the rs1801133- T and rs1801131- C alleles were all
associated with PE risk.
PMID- 28500485
TI - Hydroxyurea-Lactose Interaction Study: In Silico and In Vitro Evaluation.
AB - The Maillard reaction between hydroxyurea (a primary amine-containing drug) and
lactose (used as an excipient) was explored. The adduct of these compounds was
synthesized by heating hydroxyurea with lactose monohydrate at 60 degrees C in
borate buffer (pH 9.2) for 12 h. Synthesis of the adduct was confirmed using UV
visible spectroscopy and Fourier transform infrared, differential scanning
calorimetry, high-pressure liquid chromatography, and liquid chromatography-mass
spectrometry studies. An in silico investigation of how the adduct formation
affected the interactions of hydroxyurea with its biological target
oxyhemoglobin, to which it binds to generate nitric oxide and regulates fetal
hemoglobin synthesis, was carried out. The in silico evaluations were
complemented by an in vitro assay of the anti-sickling activity. Co-incubation of
hydroxyurea with deoxygenated blood samples reduced the percentage of sickled
cells from 38% to 12 +/- 1.6%, whereas the percentage of sickled cells in samples
treated with the adduct was 17 +/- 1.2%. This indicated loss of anti-sickling
activity in the case of the adduct. This study confirmed that hydroxyurea can
participate in a Maillard reaction if lactose is used as a diluent. Although an
extended study at environmentally feasible temperatures was not carried out in
the present investigation, the partial loss of the anti-sickling activity of
hydroxyurea was investigated along with the in silico drug-target interactions.
The results indicated that the use of lactose in hydroxyurea formulations needs
urgent reconsideration and that lactose must be replaced by other diluents that
do not form Maillard adducts.
PMID- 28500486
TI - Tips and tricks for a safe and effective image-guided percutaneous renal tumour
ablation.
AB - : Image-guide thermal ablations are nowadays increasingly used to provide a
minimally invasive treatment to patients with renal tumours, with reported good
clinical results and low complications rate. Different ablative techniques can be
applied, each with some advantages and disadvantages according to the clinical
situation. Moreover, percutaneous ablation of renal tumours might be complex in
cases where there is limited access for image guidance or a close proximity to
critical structures, which can be unintentionally injured during treatment. In
the present paper we offer an overview of the most commonly used ablative
techniques and of the most important manoeuvres that can be applied to enhance
the safety and effectiveness of percutaneous image-guided renal ablation.
Emphasis is given to the different technical aspects of cryoablation,
radiofrequency ablation, and microwave ablation, on the ideal operating room
setting, optimal image guidance, application of fusion imaging and virtual
navigation, and contrast enhanced ultrasound in the guidance and monitoring of
the procedure. Moreover, a series of protective manoeuvre that can be used to
avoid damage to surrounding sensitive structures is presented. A selection of
cases of image-guided thermal ablation of renal tumours in which the discussed
technique were used is presented and illustrated. TEACHING POINTS: *
Cryoablation, radiofrequency and microwave ablation have different advantages and
disadvantages. * US, CT, fusion imaging, and CEUS increase an effective image
guidance. * Different patient positioning and external compression may increase
procedure feasibility. * Hydrodissection and gas insufflation are useful to
displace surrounding critical structures. * Cold pyeloperfusion can reduce the
thermal damage to the collecting system.
PMID- 28500487
TI - High-frame rate vector flow imaging of the carotid bifurcation.
AB - : Carotid artery atherosclerotic disease is still a significant cause of
cerebrovascular morbidity and mortality. A new angle-independent technique,
measuring and visualizing blood flow velocities in all directions, called vector
flow imaging (VFI) is becoming available from several vendors. VFI can provide
more intuitive and quantitative imaging of vortex formation, which is not clearly
distinguishable in the color Doppler image. VFI, as quantitative method assessing
disturbed flow patterns of the carotid bifurcation, has the potential to allow
better understanding of the diagnostic value of complex flow and to enhance risk
stratification. This pictorial review article will show which new information VFI
adds for the knowledge of hemodynamics in comparison to the conventional
ultrasound techniques. TEACHING POINTS: * VFI is an angle-independent technique
measuring flow velocities in all directions. * This kind of VFI is based on a
plane wave multidirectional excitation technique. * VFI allows quantitative
assessment of carotid streamlines progression and visualizes vorticity. * VFI
does not allow a precise comprehension of streamlines' 3D shape. * VFI allows a
better understanding of carotid artery complex flows.
PMID- 28500488
TI - [Analysis of intrusion errors in free recall].
AB - Extra-list intrusion errors during five trials of the eight-word list-learning
task of the Amsterdam Dementia Screening Test (ADST) were investigated in 823
consecutive psychogeriatric patients (87.1% suffering from major neurocognitive
disorder). Almost half of the participants (45.9%) produced one or more intrusion
errors on the verbal recall test. Correct responses were lower when subjects made
intrusion errors, but learning slopes did not differ between subjects who
committed intrusion errors and those who did not so. Bivariate regression
analyses revealed that participants who committed intrusion errors were more
deficient on measures of eight-word recognition memory, delayed visual
recognition and tests of executive control (the Behavioral Dyscontrol Scale and
the ADST-Graphical Sequences as measures of response inhibition). Using
hierarchical multiple regression, only free recall and delayed visual recognition
retained an independent effect in the association with intrusion errors, such
that deficient scores on tests of episodic memory were sufficient to explain the
occurrence of intrusion errors. Measures of inhibitory control did not add
significantly to the explanation of intrusion errors in free recall, which makes
insufficient strength of memory traces rather than a primary deficit in
inhibition the preferred account for intrusion errors in free recall.
PMID- 28500489
TI - Population-based study of grade progression in patients who harboured Gleason 3 +
3.
AB - PURPOSE: This study aimed to evaluate (1) the time interval between a decision to
commence on active surveillance (AS) and grade progression in community practice;
(2) factors predicting grade progression in localised prostate cancer (CaP)
patients apparently undergoing AS. METHODS: Data from the Prostate Cancer
Outcomes Registry-Victoria were used to analyze men with Gleason 3 + 3 CaP or
less who had at least one repeat biopsy. Unadjusted and adjusted 5-year Kaplan
Meier survival curves were used to assess the time to grade progression. Both
univariate and multivariate analyses for grade progression were performed using
Cox proportional hazards. RESULTS: The cohort included 951 men. Overall, 39% of
men had Gleason grade reclassified to a higher risk disease state with median of
2.2 years [IQR 1.2-3.7 years]. Men who harboured cT2 disease were 30% more likely
to have upgrading compared to men with cT1 disease (adjusted HR: 1.3, 95% CI 1.0
1.6, p = 0.048). Half of the men with cT2 in our cohort had their Gleason grade
reclassified within 1.6 years from diagnosis as compared with 2.7 years for the
cT1 group. The presence of percentage of core involvement >25.0% and a PSA
velocity of >1.01 ng/mL/year remained significant for a higher progression rate.
The adjusted HR: 1.6; 95% CI [1.2-2.3], p = 0.004; adjusted HR: 1.6, 95% CI [1.2
2.4], p = 0.021, for percent of core involvement of 25.1-37.5%, and >=37.6%,
respectively. The adjusted HRs and p value associated with PSA velocity were 1.5;
95% CI [1.1-2.1], p = 0.016 and 1.6; 95% CI [1.2-2.3], p = 0.003 for PSA velocity
values of 1.01-2 ng/mL per year and >2 ng/mL per year, respectively. Men who were
diagnosed in regional hospital and subsequently had biopsy in metropolitan
hospital were twice at risk of having Gleason upgrade compared to those whom both
diagnostic and surveillance biopsies were carried out in metropolitan hospitals
(adjusted HR: 1.9; 95% CI 1.1-3.3, p = 0.029). CONCLUSIONS: When placing men on
AS and considering time to histologic progression, clinicians should pay
particular attention to the likely accuracy of the diagnostic specimen, their
tumour stage, volume of tumour (percent of core involvement), and rising PSA.
Those diagnosed with T2 disease and had >25.0% of core involvement, and a PSA
velocity greater than 1 ng/mL per year is at particular risk for more rapid
disease progression and, for this reason, should be counselled on the importance
of following the recommended surveillance regimen. For half of these men, their
disease will have 'progressed' according to biopsy results in 2 years.
PMID- 28500490
TI - Effects of definitive and salvage radiotherapy on the distribution of lymphocyte
subpopulations in prostate cancer patients.
AB - BACKGROUND: Radiotherapy (RT) is an established treatment for patients with
primary and recurrent prostate cancer. Herein, the effects of definitive and
salvage RT on the composition of lymphocyte subpopulations were investigated in
patients with prostate cancer to study potential immune effects. PATIENTS AND
METHODS: A total of 33 prostate cancer patients were treated with definitive (n =
10) or salvage RT (n = 23) after biochemical relapse. The absolute number of
lymphocytes and the distribution of lymphocyte subpopulations were analyzed by
multiparameter flow cytometry before RT, at the end of RT, and in the follow-up
period. RESULTS: Absolute lymphocyte counts decreased significantly after RT in
both patient groups and a significant drop was observed in the percentage of B
cells directly after RT from 10.1 +/- 1.3 to 6.0 +/- 0.7% in patients with
definitive RT and from 9.2 +/- 0.8 to 5.8 +/- 0.7% in patients with salvage RT.
In contrast, the percentages of T and natural killer (NK) cells remained
unaltered directly after RT in both patient groups. However, 1 year after RT, the
percentage of CD3+ T cells was significantly lower in patients with definitive
and salvage RT. The percentage of regulatory T cells was slightly upregulated in
primary prostate cancer patients after definitive RT, but not after salvage RT.
CONCLUSION: Definitive and salvage RT exert similar effects on the composition of
lymphocyte subpopulations in prostate cancer patients. Total lymphocyte counts
are lower in both patient groups compared to healthy controls and further
decreased after RT. B cells are more sensitive to definitive and salvage RT than
T and NK cells.
PMID- 28500491
TI - Hyperfractionated accelerated radiation therapy plus cetuximab plus cisplatin
chemotherapy in locally advanced inoperable squamous cell carcinoma of the head
and neck : Final 5-year results of a phase II study.
AB - BACKGROUND: Cetuximab (CET) is a potent inhibitor of the epidermal growth factor
receptor and has been shown to have activity in squamous cell carcinoma of the
head and neck (SCCHN). We conducted a single-arm phase II trial of a combination
therapy comprising cisplatin (CIS), CET and hyperfractionated accelerated
radiotherapy (HART). PATIENTS AND METHODS: Patients with UICC stage III or IVA/B,
M0 SCCHN were enrolled and treated with an initial dose of CET (400 mg/m2) and
then with a weekly dosage of 250 mg/m2 during HART. HART was started with a
prescribed dosage of 2.0 Gy per day for 3 weeks, followed by 1.4 Gy twice daily
to a total dose of 70.6 Gy to the gross tumour volume. CIS (40 mg/m2) was
administered weekly (days 1, 8, 15, 22, 29 and 36). The primary objective of the
phase II study was to determine the 2-year progression-free survival (PFS).
RESULTS: Between November 2007 and November 2010, a total of 74 patients were
enrolled in the study, of whom 65 were evaluable (83% were men). Median age was
56 years (range 37-69 years). An Oropharyngeal primary tumour was diagnosed in
49%, T4a,b in 65% and N2/3 in 96% of the patients. Of these patients, 85% were
smokers or ex-smokers. Complete remission (CR) was observed in 23 patients (35%).
The most common toxicity grade was >=3, including mucositis (58%) and dysphagia
(52%). The 2- and 5-year overall survival rates were 64 and 41%, the 2- and 5
year PFS rates were 45 and 32%, and the 2- and 5-year locoregional control rates
were 47 and 33%, respectively. CONCLUSION: The combination of weekly CIS with
HART plus CET is a feasible regimen for these unfavourable smoking-induced
cancers. However, the parallel US study (RTOG 0522) showed no advantage of the
enhanced triple therapy compared to chemoradiotherapy alone.
PMID- 28500493
TI - Impaired XPO5 function leads to transportation failure of microRNA precursor.
PMID- 28500492
TI - Treatment of withdrawal headache in patients with medication overuse headache: a
pilot study.
AB - BACKGROUND: Drug withdrawal still remains the key element in the treatment of
Medication Overuse Headache (MOH), but there is no consensus about the withdrawal
procedure. Still debated is the role of the steroid therapy. The aim of this
study was to evaluate the effectiveness of methylprednisolone or paracetamol in
the treatment of withdrawal headache in MOH. METHODS: We performed a pilot,
randomized, single-blinded, placebo controlled trial. MOH patients, unresponsive
to a 3 months prophylaxis, underwent withdrawal therapy on an inpatient basis.
Overused medications were abruptly stopped and methylprednisolone 500 mg i.v (A)
or paracetamol 4 g i.v. (B) or placebo i.v. (C) were given daily for 5 days.
Patients were monitored at 1 and 3 months. RESULTS: Eighty three consecutive MOH
patients were enrolled. Fifty seven patients completed the study protocol.
Nineteen patients were randomized to each group. Withdrawal headache on the 5th
day was absent in 21.0% of group A, in 31.6% of group B and in 12.5% of group C
without significant differences. Withdrawal headache intensity decreased
significantly after withdrawal without differences among the groups. Rregardless
of withdrawal treatment, 52% MOH patients reverted to an episodic migraine and
62% had no more medication overuse after 3 months. CONCLUSIONS: This study
suggests that in a population of severe MOH patients, withdrawal headache
decreased significantly in the first 5 days of withdrawal regardless of the
treatment used. Methylprednisolone and paracetamol are not superior to placebo at
the end of the detoxification program.
PMID- 28500494
TI - Three divergent approaches identified the same RGF1 receptors in Arabidopsis
thaliana.
PMID- 28500495
TI - Causes for early and late surgical re-intervention after radial head
arthroplasty.
AB - PURPOSE: The primary objective was to describe the reasons for surgical re
intervention after radial head arthroplasty. The secondary objective was to
analyze the radiographic and clinical outcomes after surgical re-intervention at
the elbow with implant conservation. METHODS: Among the 70 radial head
arthroplasties with bipolar radial head implant performed between 2002 and 2014,
29 required surgical re-interventions. Reasons for surgical re-intervention were
gathered from operative notes and follow-up documentation. Patients who underwent
re-intervention with implant retention were reassessed via clinical and
radiographic examinations by an independent reviewer. RESULTS: Twenty nine re
operations were performed at a mean follow-up of 16 +/- 11.7 months (0.2-36
months). The prosthesis was removed in 18 cases and retained in 11. There was a
significant difference in mean time to re-intervention between the implant
removal and preservation groups, 23.1 +/- 8.3 months (7-36 months) and 4.4 +/-
4.7 months (0.2-13 months), respectively (p < 0.001). The primary reason for
surgical re-intervention was painful loosening (13 cases). Radio-capitellar
instability was the most frequent reason for re-intervention with implant
retention (5 cases). Midterm quickDASH and MEPS after surgical re-intervention
with implant retention were 15.4 +/- 5.4 and 82.27 +/- 7.3, respectively. At
least one degenerative lesion was reported in nine cases (81.8%) (i.e. 5
periprosthetic osteolysis, 5 capitellar wear, 5 periarticular heterotopic
ossification). CONCLUSIONS: Painful loosening and capitellar instability are the
primary reasons for surgical re-intervention with or without implant removal.
Midterm clinical results are favourable despite an elevated rate of degenerative
lesions after surgical re-intervention with implant retention.
PMID- 28500496
TI - Patient-specific instrumentation improves alignment of lateral unicompartmental
knee replacements by novice surgeons.
AB - PURPOSE: Patient-specific instrumentation (PSI) has the potential to offer
numerous benefits-not least of all, improved resection accuracy; but its
potential has not been realised in clinical studies. An explanation may be the
focus of such studies on the total knee replacement (TKR-a common procedure, with
which surgeons are generally very familiar. Consequently, we sought to
investigate the potential role of PSI in guiding novice surgeons to perform the
more technically demanding and less familiar lateral unicondylar knee replacement
(LUKR). METHODS: Twelve orthopaedic trainees naive to LUKR were instructed to
perform the procedure according to a pre-operative plan. These were carried out
on synthetic sawbones and were completed once with conventional instrumentation
alone and once with the adjunct of PSI, allowing a comparison of the plan
adherence achieved by the two sets of instrumentation. RESULTS: There was a
tendency for PSI to demonstrate improved plan adherence, though a statistically
significant improvement was only seen in compound rotational error of the femoral
implant (p = 0.004). PSI was, however, able to produce narrower standard
deviations in the mean translational displacement of the femoral implant and also
the mean rotational displacement of both implants, suggesting a higher degree of
precision. CONCLUSIONS: Our study provides some evidence that PSI can improve the
ability of novice surgeons to replicate a pre-operative plan, but our results
suggest the need for larger-scale clinical studies to establish the role of PSI
in this procedure.
PMID- 28500498
TI - [Aging, technical aids, and the socio-gerontological dialog-the IDA
interdisciplinary guide].
PMID- 28500497
TI - Evaluation of endothelialization in the center part of graft using 3 cm vascular
grafts implanted in the abdominal aortae of the rat.
AB - In order to develop small-diameter vascular grafts, it is necessary to evaluate
endothelialization, especially, in the center part at early stage. For
implantation of vascular grafts of 1 cm in length to abdominal aortae of rat,
endothelial cells can be formed easily by stretching anastomosis. We evaluated
the endothelialization in the center part of vascular grafts by implanting
vascular grafts using transgenic (TG) silk fibroin (SF) of 3 cm in length.
Vascular grafts were prepared 1.5 mm in diameter and 1 and 3 cm in length using
wild type (WT) SF and TG SF by braiding structure, respectively. The grafts were
removed after 2 weeks or 3 months and evaluated pathologically.
Endothelialization was not confirmed totally after 3 months of implantation.
However, endothelialization in the center part of grafts was significantly higher
in TG SF than in WT SF. No significant difference was found regarding tissue
infiltration and internal diameter. The TG SF revealed migration of the
endothelial cells into the center part of the vessels at the early stage. Also,
tissue infiltration and remodeling is expected using SF. The 3 cm length vascular
grafts can be evaluated as a new experimental system.
PMID- 28500499
TI - [Anesthesiological care of trauma patients in orthogeriatric co-management].
AB - Elderly patients increasingly need to undergo surgery under anesthesia,
especially following trauma. A timely interdisciplinary approach to the
perioperative management of these patients is decisive for the long-term outcome.
Orthogeriatric co-management, which includes geriatricians and anesthesiologists
from an early stage, is of great benefit for geriatric patients. Patient age,
comorbidities and self-sufficiency in activities of daily life are decisive for
an anesthesiological assessment of the state of health and preoperative risk
stratification. If necessary additional investigations, such as echocardiography
must be carried out, in order to guarantee optimal perioperative
anesthesiological management. Certain medical factors can delay the initiation of
anesthesia and it is absolutely necessary that these are taken into consideration
for surgical management. Not every form of anesthesia is equally suitable for
every geriatric patient.
PMID- 28500500
TI - [Epistemology in the intensive care unit-what is the purpose of a definition? :
Paradigm shift in sepsis research].
AB - The adoption of the new sepsis definition in early 2016 introduced a new paradigm
for the clinical picture of sepsis. Up until now, sepsis was defined as a
systemic inflammatory reaction (systemic inflammatory response syndrome, SIRS) to
an infection. Based on a better understanding of the molecular mechanisms, the
focus of the new definition is no longer the inflammatory response, but rather
the tissue damage and impairment of organ function which this induces. The
paradigm thus moves away from the infection and the systemic inflammatory
response, and toward that which makes sepsis so dangerous in terms of both
disease dynamics and outcome: organ failure due to a dysregulated host response
to an infection. This change of perspective or paradigm enables patients with an
increased risk of developing sepsis to be recognized and treated earlier in
clinical routine, even outside of the intensive care unit. The new definition
also promotes development of new treatment strategies with improved ability to
treat sepsis causally.
PMID- 28500501
TI - "Can One Put Faith and Work in the Same Sentence?" Faith Development and Vocation
of a Female Leader in the Engineering Profession.
AB - Faith has been pointed out as a possible resource in strengthening individuals'
health and well-being at work. The aim of this article is to gain in-depth
knowledge of the faith development and vocation of a selected female leader in a
male-dominated work context. The article contributes to research on faith
development in women leaders, based on Fowler's faith development theory. This is
a single case study grounded in a qualitative research design. In-depth
qualitative data were gathered through observation and interviews over 18 months.
Findings showed the development of faith across a women leader's life span and
highlight that faith and vocation are important resources that provide strength,
meaningfulness and a vision.
PMID- 28500502
TI - Retinoic acid regulates cell-shape and -death of E-FABP (FABP5)-immunoreactive
septoclasts in the growth plate cartilage of mice.
AB - Septoclasts, which are mononuclear and spindle-shaped cells with many processes,
have been considered to resorb the transverse septa of the growth plate (GP)
cartilage at the chondro-osseous junction (COJ). We previously reported the
expression of epidermal-type fatty acid-binding protein (E-FABP, FABP5) and
localization of peroxisome proliferator-activated receptor (PPAR)beta/delta,
which mediates the cell survival or proliferation, in septoclasts. On the other
hand, retinoic acid (RA) can bind to E-FABP and is stored abundantly in the GP
cartilage. From these information, it is possible to hypothesize that RA in the
GP is incorporated into septoclasts during the cartilage resorption and regulates
the growth and/or death of septoclasts. To clarify the mechanism of the cartilage
resorption induced by RA, we administered an overdose of RA or its precursor
vitamin A (VA)-deficient diet to young mice. In mice of both RA excess and VA
deficiency, septoclasts decreased in the number and cell size in association with
shorter and lesser processes than those in normal mice, suggesting a substantial
suppression of resorption by septoclasts in the GP cartilage. Lack of
PPARbeta/delta-expression, TUNEL reaction, RA receptor (RAR)beta, and cellular
retinoic acid-binding protein (CRABP)-II were induced in E-FABP-positive
septoclasts under RA excess, suggesting the growth arrest/cell-death of
septoclasts, whereas cartilage-derived retinoic acid-sensitive protein (CD-RAP)
inducing the cell growth arrest or morphological changes was induced in
septoclasts under VA deficiency. These results support and do not conflict with
our hypothesis, suggesting that endogenous RA in the GP is possibly incorporated
in septoclasts and utilized to regulate the activity of septoclasts resorbing the
GP cartilage.
PMID- 28500504
TI - Delay discounting and parental monitoring in adolescents with poorly controlled
type 1 diabetes.
AB - In a sample of adolescents with poorly controlled type 1 diabetes, this study
examined if delay discounting, the extent to which individuals prefer immediate
over delayed rewards, was associated with severity of non-adherence and poor
glycemic control, and if parental monitoring of diabetes management moderated
those associations. Sixty-one adolescents (M age = 15.08 years, SD 1.43) with
poorly controlled type 1 diabetes completed a delayed discounting task and an
HbA1c blood test. Adherence was assessed via self-monitoring of blood glucose
(SMBG) data from adolescents' glucometers. Parents completed a parental
monitoring questionnaire. Greater delay discounting was associated with higher
HbA1c, but not SMBG. Direct parent observation of diabetes tasks, but not
indirect parental monitoring, moderated the link between greater delay
discounting and higher HbA1c, with higher direct parent observation buffering the
link between greater discounting and poorer glycemic control. Delay discounting
may be a target for future interventions to improve HbA1c in youth with type 1
diabetes.
PMID- 28500505
TI - Rehydration improves the ductility of dry bone allografts.
AB - Processing of bone allografts improves infectious safety and allows storing bone
substitutes at room temperature. The aim of this study was to compare mechanical
properties of the processed OsteopureTM bone with fresh frozen bone. All the
samples were pieces from femoral heads retrieved during hip arthroplasty
operations. The processing includes chemical decellularization, drying and
irradiation with 25 kGy. Three types of samples were tested: 1. fresh frozen
thawed wet, 2. dry non-rehydrated graft 3. dry rehydrated graft. In the 3-point
bending test Young's modulus and stress at break yielded no significant
difference among the 3 different sample groups. Rehydrating of the dry graft
showed increased ductility in strain at break test compared with the other 2
groups (p = 0.003). In compression tests dry grafts had significantly higher
maximum effective stress and apparent maximum deformation compared with the
grafts of other groups (p < 0.05). Processed bone has almost similar mechanical
properties compared with fresh frozen bone. However, rehydration of processed dry
graft increases its ductility. These grafts may tolerate bending forces better
before breakage.
PMID- 28500503
TI - Expression and localization of myosin VI in developing mouse spermatids.
AB - Myosin VI (MVI) is a versatile actin-based motor protein that has been implicated
in a variety of different cellular processes, including endo- and exocytic
vesicle trafficking, Golgi morphology, and actin structure stabilization. A role
for MVI in crucial actin-based processes involved in sperm maturation was
demonstrated in Drosophila. Because of the prominence and importance of actin
structures in mammalian spermiogenesis, we investigated whether MVI was
associated with actin-mediated maturation events in mammals. Both
immunofluorescence and ultrastructural analyses using immunogold labeling showed
that MVI was strongly linked with key structures involved in sperm development
and maturation. During the early stage of spermiogenesis, MVI is associated with
the Golgi and with coated and uncoated vesicles, which fuse to form the acrosome.
Later, as the acrosome spreads to form a cap covering the sperm nucleus, MVI is
localized to the acroplaxome, an actin-rich structure that anchors the acrosome
to the nucleus. Finally, during the elongation/maturation phase, MVI is
associated with the actin-rich structures involved in nuclear shaping: the
acroplaxome, manchette, and Sertoli cell actin hoops. Since this is the first
report of MVI expression and localization during mouse spermiogenesis and MVI
partners in developing sperm have not yet been identified, we discuss some
probable roles for MVI in this process. During early stages, MVI is hypothesized
to play a role in Golgi morphology and function as well as in actin dynamics
regulation important for attachment of developing acrosome to the nuclear
envelope. Next, the protein might also play anchoring roles to help generate
forces needed for spermatid head elongation. Moreover, association of MVI with
actin that accumulates in the Sertoli cell ectoplasmic specialization and other
actin structures in surrounding cells suggests additional MVI functions in
spermatid movement across the seminiferous epithelium and in sperm release.
PMID- 28500506
TI - A controlled comparison of the BacT/ALERT(r) 3D and VIRTUOTM microbial detection
systems.
AB - The performance of the next-generation BacT/ALERT(r) VIRTUOTM Microbial Detection
System (VIRTUOTM, bioMerieux Inc., Hazelwood, MO) was compared to the
BacT/ALERT(r) 3D Microbial Detection System (3D, bioMerieux Inc., Durham, NC)
using BacT/ALERT(r) FA Plus (FA Plus), BacT/ALERT(r) PF Plus (PF Plus),
BacT/ALERT(r) FN Plus (FN Plus), BacT/ALERT(r) Standard Aerobic (SA), and
BacT/ALERT(r) Standard Anaerobic (SN) blood culture bottles (bioMerieux Inc.,
Durham, NC). A seeded limit of detection (LoD) study was performed for each
bottle type in both systems. The LoD studies demonstrated that both systems were
capable of detecting organisms at nearly identical levels [<10 colony-forming
units (CFU) per bottle], with no significant difference. Following LoD
determination, a seeded study was performed to compare the time to detection
(TTD) between the systems using a panel of clinically relevant microorganisms
inoculated at or near the LoD with 0, 4, or 10 mL of healthy human blood.
VIRTUOTM exhibited a faster TTD by an average of 3.5 h, as well as demonstrated a
significantly improved detection rate of 99.9% compared to 98.8% with 3D (p-value
<0.05).
PMID- 28500508
TI - The whereabouts of visual attention: Involuntary attentional bias toward the
default gaze direction.
AB - This study proposed and verified a new hypothesis on the relationship between
gaze direction and visual attention: attentional bias by default gaze direction
based on eye-head coordination. We conducted a target identification task in
which visual stimuli appeared briefly to the left and right of a fixation cross.
In Experiment 1, the direction of the participant's head (aligned with the body)
was manipulated to the left, front, or right relative to a central fixation
point. In Experiment 2, head direction was manipulated to the left, front, or
right relative to the body direction. This manipulation was based on results
showing that bias of eye position distribution was highly correlated with head
direction. In both experiments, accuracy was greater when the target appeared at
a position where the eyes would potentially be directed. Consequently, eye-head
coordination influences visual attention. That is, attention can be automatically
biased toward the location where the eyes tend to be directed.
PMID- 28500507
TI - Impact of severe hematological abnormalities in the outcome of hospitalized
patients with influenza virus infection.
AB - Although hematological abnormalities have been described among patients with
influenza virus infection, little is known about their impact on the outcome of
the patients. The aim of this study was to assess the frequency and clinical
impact of severe hematological abnormalities in patients with confirmed influenza
virus infection. This was an observational retrospective study including all
adult patients with diagnosis of influenza virus infection hospitalized from
January to May 2016 in our institution. Influenza virus infection was diagnosed
by means of rRT-PCR assay performed on respiratory samples. Poor outcome was
defined as a composite endpoint in which at least one of the following criteria
had to be fulfilled: (a) respiratory failure, (b) SOFA >=2, or (c) death. Two
hundred thirty-nine patients were included. Applying the HLH-04 criteria for the
diagnosis of hemophagocytic syndrome, cytopenias (hemoglobin <=9 g/dl, platelets
<100,000/MUl or neutrophils <1,000/MUl) were present in 51 patients (21%).
Patients with hematological abnormalities showed higher SOFA scores, respiratory
failure, septic shock and in-hospital mortality than the remaining patients. The
composite endpoint was present in 33.3% in the cytopenias group vs. 13.3% in the
group without cytopenias (p=0.001). In a multivariate analysis, variables
associated with the composite endpoint were: use of steroids prior to present
admission (OR: 0.12; 95% CI: 0.015-0.96, p=0.046), presence of any hematological
abnormality (OR: 3.54; 95% CI:1.66-7.51, p= 0.001), and LDH>225 U/l (OR:4.45;
CI:1-19.71, p=0.049). Hematological abnormalities are not uncommon among
hospitalized patients with influenza virus infection, and they are associated
with a poorer outcome.
PMID- 28500509
TI - Observations of termitarium geophagy by Rylands' bald-faced saki monkeys
(Pithecia rylandsi) in Madre de Dios, Peru.
AB - Geophagy, or soil consumption, has been documented in diverse animal taxa,
including many primates. Physiological functions such as mineral supplementation,
detoxification of secondary compounds, and antacid properties are possible causes
for this behavior. We report on observations of geophagy at arboreal termitaria
by free-ranging Pithecia rylandsi at La Estacion Biologica Los Amigos (EBLA) in
Peru between 2008 and 2015. Characteristics of geophagy events, including saki
monkey behavior at the termitaria, were recorded and geochemical analyses were
conducted on consumed termitaria, nearby topsoils, and unvisited termitaria. We
observed 76 feeding bouts at 26 different termitaria by two groups of P. rylandsi
during 1125 observational hours (0.07 bouts/obs. h). Geophagy occurred throughout
the year, but rates peaked in January during the rainy season. All age and sex
classes visited both active and inactive mounds. Feeding bouts were brief (171 +/
SD 154 s), and no differences were observed in time spent feeding at active or
inactive termitaria. Analyses showed that consumed soils contained higher
concentrations of phosphorous, potassium, calcium, and magnesium than did
topsoil. Consumed soils also contained a higher total cation exchange capacity
than topsoil. Our analysis of consumed versus control termitaria revealed no
differences in their chemical composition. We discuss these results in the
context of the two primary hypotheses proposed for geophagy in pitheciins:
mineral supplementation and toxin adsorption. Our data are consistent with the
interpretation that P. rylandsi consume soils from arboreal termitaria to aid in
adsorption of toxins found in immature seeds, which are a year-round component of
their diet.
PMID- 28500513
TI - Erratum to: Surgeons' views on sling tensioning during surgery for female stress
urinary incontinence.
PMID- 28500512
TI - Molecular Adaptations to Social Defeat Stress and Induced Depression in Mice.
AB - Chronic stress is a risk factor for major depression. Social defeat stress is a
well-validated murine model of depression. However, little is known about the
gene activity dynamics during the development of a depression-like state. We
analyzed the effects of social defeat stress of varying duration (10 and 30 days)
on the behavioral patterns and prefrontal-cortex transcriptome of C57BL/6 mice.
The 10-day exposure to social defeat stress resulted in a high level of social
avoidance with no signs of depression-associated behavior. Most animals exposed
to 30 days of social defeat stress demonstrated clear hallmarks of depression,
including a higher level of social avoidance, increased immobility in the forced
swimming test, and anhedonic behavior. The monitoring of transcriptome changes
revealed widespread alterations in gene expression on the 10th day. Surprisingly,
the expression of only a few genes were affected by the 30th day of stress,
apparently due to a reversal of the majority of the early stress-induced changes
to the original basal state. Moreover, we have found that glucocorticoid
sensitive genes are clearly stimulated targets on the 10th day of stress, but
these genes stop responding to the elevated corticosterone level by the 30th day
of stress. The majority of genes altered by the 30-day stress were downregulated,
with the most relevant ones participating in chromatin modifications and
neuroplasticity (e.g., guanine nucleotide exchange factors of the Rho-family of
GTPases). Very different molecular responses occur during short-term and long
term social stress in mice. The early-stress response is associated with social
avoidance and with upregulation and downregulation of many genes, including those
related to signal transduction and cell adhesion pathways. Downregulation of a
few genes, in particular, genes for histone-modifying methyltransferases, is a
signature response to prolonged stress that induces symptoms of depression.
Altogether, our data show that the development of depression under social stress
conditions is correlated with suppression of the overactive molecular response to
induced stress, involving gene regulatory resistance to glucocorticoid molecules,
potentially via a chromatin remodeling mechanism.
PMID- 28500515
TI - Outpatient mid-urethral tissue fixation system sling for urodynamic stress
urinary incontinence: 3-year surgical and quality of life results.
AB - INTRODUCTION: To evaluate the clinical effectiveness and quality of life (QOL) of
outpatient mid-urethral tissue fixation system sling (TFS) procedures for
urodynamic stress urinary incontinence (SUI) at 3-year follow-up. METHODS: We
analyzed 50 mid-urethral TFS sling operations between 2007 and 2012 at Yokohama
Motomachi Women's Clinic LUNA. The primary outcome was success defined as a
negative 24-h pad test, negative cough and Valsalva stress test, and no re
treatment for SUI. Secondary outcome was improvement in quality of life, which
was assessed using the Incontinence Questionnaire-Short Form (ICIQ-SF) and the
Incontinence Impact Questionnaire Short Form (IIQ-7). The 3-year postoperative
scores were compared with baseline scores using the Wilcoxon signed rank test. A
5% two-sided significance level was used for all statistical testing. RESULTS:
All operations were carried out on an outpatient basis with no intraoperative
complications. The primary cure rate result at 3-year follow-up was 90%. Median
total ICIQ-SF score changed from 12 (6-20) to 0 (0-14) and median total IIQ-7
score changed from 156 (0-300) to 0 (0.00-16.7) at 3-year follow-up. CONCLUSIONS:
Results show that the TFS mid-urethral sling operation is a simple, safe,
effective procedure that may be done without difficulty at a freestanding clinic
on an outpatient basis and favorably improves subjective QOL of the patient.
PMID- 28500516
TI - Nd:YAG laser irradiation associated with fluoridated gels containing photo
absorbers in the prevention of enamel erosion.
AB - This study evaluated the combined effect of Nd:YAG laser irradiation and
fluoridated gels containing photo absorbers against enamel erosion. Enamel
specimens from bovine teeth were polished, eroded (10 min, with 1% citric acid,
pH = 2.6), and randomly allocated into the experimental groups (n = 8), according
to the different surface treatments: fluoridated gels (F: 9047 ppm F and F + Sn:
9047 ppm F and 3000 ppm Sn), with or without photo absorbers (E: erythrosine and
MB: methylene blue), and associated or not with Nd:YAG laser irradiation (in
contact; 0.5 W; 50 mJ; ~41.66 J/cm2; 10 Hz; 40 s; pulse duration of 120 MUs). A
placebo gel (PLA) associated or not with laser was used as control. All gels had
pH = 4.5 and were applied for 2 min. Laser irradiation was performed during gel
application. The specimens were then submitted to a 5-day erosion
remineralization cycling model using 0.3% citric acid (pH = 2.6), 4*/day. Enamel
surface loss (SL) was analyzed by optical profilometry in the end of the cycling
(in MUm). Data were analyzed by ANOVA and Tukey tests (alpha = 0.05). Means (SD)
of SL for the groups were the following (different superscript letters imply
significant difference among groups): PLA (21.02 +/- 1.28)a, PLA + laser (19.20
+/- 0.96)ab, laser (17.47 +/- 1.50)b, F + Sn + E + laser (13.69 +/- 0.62)c, F + E
+ laser (13.52 +/- 1.16)c, F (13.10 +/- 1.08)c, F + laser (11.94 +/- 1.44)cd, F +
Sn + MB + laser (11.90 +/- 4.02)cd, F + MB + laser (11.42 +/- 1.42)cd, F + Sn
(11.12 +/- 1.20)cd, and F + Sn + laser (10.35 +/- 0.89)d. In conclusion, all
fluoridated gels and the Nd:YAG laser irradiation reduced erosion development,
but the combination of treatments did not promote further protection. The
addition of photo absorbers to the fluoridated gels did not influence the anti
erosive effect of the combination of laser plus fluoridated gels.
PMID- 28500517
TI - Role of Non-Statins, LDL-C Thresholds, and Special Population Considerations: A
Look at the Updated 2016 ACC Consensus Committee Recommendations.
AB - PURPOSE OF REVIEW: The 2013 ACC/AHA Cholesterol guidelines was a major paradigm
shift in the management and treatment of dyslipidemia. The new guidelines
outlined "statin benefit groups," highlighted weighing the benefit versus risks
of statin therapy ("net benefit"), and discussed the importance of shared
decision making between patients and providers in primary prevention. While there
was widespread agreement on the main groups benefiting from statin therapy, there
was significant controversy regarding LDL-C goals and thresholds, the role of non
statin therapy, and the use of statins in specific populations. The goal of this
review is to understand the rationale for the updated 2016 ACC Expert Consensus
on Non-Statins and to contrast it with the 2015 NLA Recommendations on the
Management of Dyslipidemia. RECENT FINDINGS: The findings of the ACC Expert
Consensus Panel were largely influenced by the results of several new clinical
trials using non-statin therapy in combination with moderate to high intensity
statin therapy. The IMPROVE-IT trial demonstrated that ezetimibe on top of statin
therapy lowered ASCVD risk in patients with acute coronary syndromes whose LDL
was driven below the previous LDL-C target of <70 mg/dL. In addition, preliminary
data assessing the safety of evolocumab and alirocumab on top of statin therapy
suggested possible large reductions in ASCVD risk in post hoc analysis. Both the
2016 ACC Consensus Recommendations and the 2015 NLA Recommendations emphasize the
importance of maximally tolerated statin therapy, the use of adjunctive non
statin LDL lowering therapy, and the use of LDL-C goals and thresholds to guide
intensification of LDL lowering therapy. Although there are some important
differences between the ACC Consensus and NLA recommendations in terms of
treatment of special populations (i.e., CHF) and on the use of non-HDL-C goals
and thresholds, both guidelines support a role for ezetimibe, bile acid
sequestrants, and PCSK-9 inhibitors in patients on maximum tolerated statin
therapy. The recent positive results of the FOURIER trial gives additional
support to the non-statin recommendations of both the ACC and NLA.
PMID- 28500518
TI - Incremental start to PD as experienced in Italy: results of censuses carried out
from 2005 to 2014.
AB - BACKGROUND: It is not known how widely used in Italy an incremental start to in
peritoneal dialysis (Incr-PD) is. METHODS: By analyzing the peritoneal dialysis
(PD) censuses conducted by the PD Study Group (GSDP-SIN) for the years 2005,
2008, 2010, 2012 and 2014 in all the Centers performing PD in Italy, the use of
Incr-PD, i.e. continuous ambulatory peritoneal dialysis (CAPD) with 1 or 2
exchanges/day or automated peritoneal dialysis (APD) with 3-4 sessions/week, was
examined among incident PD patients. RESULTS: In 2014 PD was started in Italy by
1,652 patients, 455 (27.5%) of whom incrementally (Incr-CAPD 82.2% vs. Incr-APD
17.8%). Incr-PD was used in 53.5% of the 225 Centers. The number of patients and
of Centers using Incr-DP increased constantly over the years up to 2012 (in 2005
Incr-PD was used in 33.4% of Centers, and in 11.9% of patients). The use of Incr
PD was greater in Centers with a more extensive PD program and greater use of PD
in general. The most widely-used modality in Incr-PD was CAPD. CONCLUSIONS: Incr
PD is used in Italy in a large number of incident PD patients. The reasons for
this increase need to be clarified, as current adequacy targets are based on full
dose studies with a very low glomerular filtration rate (GFR).
PMID- 28500519
TI - DFT study of CO2 and H2O co-adsorption on carbon models of coal surface.
AB - The moisture content of coal affects the adsorption capacity of CO2 on the coal
surface. Since the hydrogen bonds are formed between H2O and oxygen functional
group, the H2O cluster more easily adsorbs on the coal micropore than CO2
molecule. The coal micropores are occupied by H2O molecules that cannot provide
extra space for CO2 adsorption, which may leads to the reduction of CO2
adsorption capacity. However, without considering factors of micropore and oxygen
functional groups, the co-adsorption mechanisms of CO2 and adsorbed H2O molecule
are not clear. Density functional theory (DFT) calculations were performed to
elucidate the effect of adsorbed H2O to CO2 adsorption. This study reports some
typical coal-H2O...CO2 complexes, along with a detailed analysis of the geometry,
energy, electrostatic potential (ESP), atoms in molecules (AIM), reduced density
gradient (RDG), and energy decomposition analysis (EDA). The results show that
H2O molecule can more stably adsorb on the aromatic ring surface than CO2
molecule, and the absolute values of local ESP maximum and minimum of H2O cluster
are greater than CO2. AIM analysis shows a detailed interaction path and strength
between atoms in CO2 and H2O, and RDG analysis shows that the interactions among
CO2, H2O, and coal model belong to weak van der Waals force. EDA indicates that
electrostatic and long-range dispersion terms play a primary role in the co
adsorption of CO2 and H2O. According to the DFT calculated results without
considering micropore structure and functional group, it is shown that the
adsorbed H2O can promote CO2 adsorption on the coal surface. These results
demonstrate that the micropore factor plays a dominant role in affecting CO2
adsorption capacity, the attractive interaction of adsorbed H2O to CO2 makes
little contribution.
PMID- 28500520
TI - Theoretical study of noncovalent interactions in XCN...YO2H (X = F, Cl, Br, I; Y
= P, As, Sb) complexes.
AB - Noncovalent interactions in XCN...YO2H (X = F, Cl, Br, I; Y = P, As, Sb)
complexes were investigated using ab initio calculations at the MP2/aug-cc-pVDZ
level of theory. There are four different configurations of these complexes, and
the complexes are formed via hydrogen bonds, halogen bonds, pi-hole interactions,
or dual interactions. An examination of binding distances and interaction
energies suggested that pi-hole bonds are more stable than the other
interactions. Molecular electrostatic potentials, electron densities, second
order stabilization energies, and electron density differences were computed to
study the character of these interactions.
PMID- 28500521
TI - Overview of the Diverse Roles of Bacterial and Archaeal Cytoskeletons.
AB - As discovered over the past 25 years, the cytoskeletons of bacteria and archaea
are complex systems of proteins whose central components are dynamic cytomotive
filaments. They perform roles in cell division, DNA partitioning, cell shape
determination and the organisation of intracellular components. The protofilament
structures and polymerisation activities of various actin-like, tubulin-like and
ESCRT-like proteins of prokaryotes closely resemble their eukaryotic counterparts
but show greater diversity. Their activities are modulated by a wide range of
accessory proteins but these do not include homologues of the motor proteins that
supplement filament dynamics to aid eukaryotic cell motility. Numerous other
filamentous proteins, some related to eukaryotic IF-proteins/lamins and dynamins
etc, seem to perform structural roles similar to those in eukaryotes.
PMID- 28500522
TI - E. coli Cell Cycle Machinery.
AB - Cytokinesis in E. coli is organized by a cytoskeletal element designated the Z
ring. The Z ring is formed at midcell by the coalescence of FtsZ filaments
tethered to the membrane by interaction of FtsZ's conserved C-terminal peptide
(CCTP) with two membrane-associated proteins, FtsA and ZipA. Although interaction
between an FtsZ monomer and either of these proteins is of low affinity, high
affinity is achieved through avidity - polymerization linked CCTPs interacting
with the membrane tethers. The placement of the Z ring at midcell is ensured by
antagonists of FtsZ polymerization that are positioned within the cell and target
FtsZ filaments through the CCTP. The placement of the ring is reinforced by a
protein network that extends from the terminus (Ter) region of the chromosome to
the Z ring. Once the Z ring is established, additional proteins are recruited
through interaction with FtsA, to form the divisome. The assembled divisome is
then activated by FtsN to carry out septal peptidoglycan synthesis, with a
dynamic Z ring serving as a guide for septum formation. As the septum forms, the
cell wall is split by spatially regulated hydrolases and the outer membrane
invaginates in step with the aid of a transenvelope complex to yield progeny
cells.
PMID- 28500526
TI - Intermediate Filaments Supporting Cell Shape and Growth in Bacteria.
AB - For years intermediate filaments (IF), belonging to the third class of
filamentous cytoskeletal proteins alongside microtubules and actin filaments,
were thought to be exclusive to metazoan cells. Structurally these eukaryote IFs
are very well defined, consisting of globular head and tail domains, which flank
the central rod-domain. This central domain is dominated by an alpha-helical
secondary structure predisposed to form the characteristic coiled-coil, parallel
homo-dimer. These elementary dimers can further associate, both laterally and
longitudinally, generating a variety of filament-networks built from filaments in
the range of 10 nm in diameter. The general role of these filaments with their
characteristic mechano-elastic properties both in the cytoplasm and in the
nucleus of eukaryote cells is to provide mechanical strength and a scaffold
supporting diverse shapes and cellular functions.Since 2003, after the first
bacterial IF-like protein, crescentin was identified, it has been evident that
bacteria also employ filamentous networks, other than those built from bacterial
tubulin or actin homologues, in order to support their cell shape, growth and, in
some cases, division. Intriguingly, compared to their eukaryote counterparts, the
group of bacterial IF-like proteins shows much wider structural diversity. The
sizes of both the head and tail domains are markedly reduced and there is great
variation in the length of the central rod-domain. Furthermore, bacterial rod
domains often lack the sub-domain organisation of eukaryote IFs that is the
defining feature of the IF-family. However, the fascinating display of
filamentous assemblies, including rope, striated cables and hexagonal laces
together with the conditions required for their formation both in vitro and in
vivo strongly resemble that of eukaryote IFs suggesting that these bacterial
proteins are deservedly classified as part of the IF-family and that the current
definition should be relaxed slightly to allow their inclusion. The lack of
extensive head and tail domains may well make the bacterial proteins more
amenable for structural characterisation, which will be essential for
establishing the mechanism for their association into filaments. What is more,
the well-developed tools for bacterial manipulations provide an excellent
opportunity of studying the bacterial systems with the prospect of making
significant progress in our understanding of the general underlying principles of
intermediate filament assemblies.
PMID- 28500525
TI - FtsZ Constriction Force - Curved Protofilaments Bending Membranes.
AB - FtsZ assembles in vitro into protofilaments (pfs) that are one subunit thick and
~50 subunits long. In vivo these pfs assemble further into the Z ring, which,
along with accessory division proteins, constricts to divide the cell. We have
reconstituted Z rings in liposomes in vitro, using pure FtsZ that was modified
with a membrane targeting sequence to directly bind the membrane. This FtsZ-mts
assembled Z rings and constricted the liposomes without any accessory proteins.
We proposed that the force for constriction was generated by a conformational
change from straight to curved pfs. Evidence supporting this mechanism came from
switching the membrane tether to the opposite side of the pf. These switched
tether pfs assembled "inside-out" Z rings, and squeezed the liposomes from the
outside, as expected for the bending model. We propose three steps for the full
process of cytokinesis: (a) pf bending generates a constriction force on the
inner membrane, but the rigid peptidoglycan wall initially prevents any
invagination; (b) downstream proteins associate to the Z ring and remodel the
peptidoglycan, permitting it to follow the constricting FtsZ to a diameter of
~250 nm; the final steps of closure of the septum and membrane fusion are
achieved by excess membrane synthesis and membrane fluctuations.
PMID- 28500527
TI - FtsZ-ring Architecture and Its Control by MinCD.
AB - In bacteria and archaea, the most widespread cell division system is based on the
tubulin homologue FtsZ protein, whose filaments form the cytokinetic Z-ring. FtsZ
filaments are tethered to the membrane by anchors such as FtsA and SepF and are
regulated by accessory proteins. One such set of proteins is responsible for Z
ring's spatiotemporal regulation, essential for the production of two equal-sized
daughter cells. Here, we describe how our still partial understanding of the FtsZ
based cell division process has been progressed by visualising near-atomic
structures of Z-rings and complexes that control Z-ring positioning in cells,
most notably the MinCDE and Noc systems that act by negatively regulating FtsZ
filaments. We summarise available data and how they inform mechanistic models for
the cell division process.
PMID- 28500528
TI - Bacterial Actins.
AB - A diverse set of protein polymers, structurally related to actin filaments
contributes to the organization of bacterial cells as cytomotive or cytoskeletal
filaments. This chapter describes actin homologs encoded by bacterial
chromosomes. MamK filaments, unique to magnetotactic bacteria, help establishing
magnetic biological compasses by interacting with magnetosomes. Magnetosomes are
intracellular membrane invaginations containing biomineralized crystals of iron
oxide that are positioned by MamK along the long-axis of the cell. FtsA is
widespread across bacteria and it is one of the earliest components of the
divisome to arrive at midcell, where it anchors the cell division machinery to
the membrane. FtsA binds directly to FtsZ filaments and to the membrane through
its C-terminus. FtsA shows altered domain architecture when compared to the
canonical actin fold. FtsA's subdomain 1C replaces subdomain 1B of other members
of the actin family and is located on the opposite side of the molecule.
Nevertheless, when FtsA assembles into protofilaments, the protofilament
structure is preserved, as subdomain 1C replaces subdomain IB of the following
subunit in a canonical actin filament. MreB has an essential role in shape
maintenance of most rod-shaped bacteria. Unusually, MreB filaments assemble from
two protofilaments in a flat and antiparallel arrangement. This non-polar
architecture implies that both MreB filament ends are structurally identical.
MreB filaments bind directly to membranes where they interact with both cytosolic
and membrane proteins, thereby forming a key component of the elongasome. MreB
filaments in cells are short and dynamic, moving around the long axis of rod
shaped cells, sensing curvature of the membrane and being implicated in
peptidoglycan synthesis.
PMID- 28500524
TI - Cytoskeletal Proteins in Caulobacter crescentus: Spatial Orchestrators of Cell
Cycle Progression, Development, and Cell Shape.
AB - Caulobacter crescentus, an aquatic Gram-negative alpha-proteobacterium, is
dimorphic, as a result of asymmetric cell divisions that give rise to a free
swimming swarmer daughter cell and a stationary stalked daughter. Cell polarity
of vibrioid C. crescentus cells is marked by the presence of a stalk at one end
in the stationary form and a polar flagellum in the motile form. Progression
through the cell cycle and execution of the associated morphogenetic events are
tightly controlled through regulation of the abundance and activity of key
proteins. In synergy with the regulation of protein abundance or activity,
cytoskeletal elements are key contributors to cell cycle progression through
spatial regulation of developmental processes. These include: polarity
establishment and maintenance, DNA segregation, cytokinesis, and cell elongation.
Cytoskeletal proteins in C. crescentus are additionally required to maintain its
rod shape, curvature, and pole morphology. In this chapter, we explore the
mechanisms through which cytoskeletal proteins in C. crescentus orchestrate
developmental processes by acting as scaffolds for protein recruitment,
generating force, and/or restricting or directing the motion of molecular
machines. We discuss each cytoskeletal element in turn, beginning with those
important for organization of molecules at the cell poles and chromosome
segregation, then cytokinesis, and finally cell shape.
PMID- 28500529
TI - Bacterial Nucleoid Occlusion: Multiple Mechanisms for Preventing Chromosome
Bisection During Cell Division.
AB - In most bacteria cell division is driven by the prokaryotic tubulin homolog,
FtsZ, which forms the cytokinetic Z ring. Cell survival demands both the spatial
and temporal accuracy of this process to ensure that equal progeny are produced
with intact genomes. While mechanisms preventing septum formation at the cell
poles have been known for decades, the means by which the bacterial nucleoid is
spared from bisection during cell division, called nucleoid exclusion (NO), have
only recently been deduced. The NO theory was originally posited decades ago
based on the key observation that the cell division machinery appeared to be
inhibited from forming near the bacterial nucleoid. However, what might drive the
NO process was unclear. Within the last 10 years specific proteins have been
identified as important mediators of NO. Arguably the best studied NO mechanisms
are those employed by the Escherichia coli SlmA and Bacillus subtilis Noc
proteins. Both proteins bind specific DNA sequences within selected chromosomal
regions to act as timing devices. However, Noc and SlmA contain completely
different structural folds and utilize distinct NO mechanisms. Recent studies
have identified additional processes and factors that participate in preventing
nucleoid septation during cell division. These combined data show multiple levels
of redundancy as well as a striking diversity of mechanisms have evolved to
protect cells against catastrophic bisection of the nucleoid. Here we discuss
these recent findings with particular emphasis on what is known about the
molecular underpinnings of specific NO machinery and processes.
PMID- 28500523
TI - Cell Cycle Machinery in Bacillus subtilis.
AB - Bacillus subtilis is the best described member of the Gram positive bacteria. It
is a typical rod shaped bacterium and grows by elongation in its long axis,
before dividing at mid cell to generate two similar daughter cells. B. subtilis
is a particularly interesting model for cell cycle studies because it also
carries out a modified, asymmetrical division during endospore formation, which
can be simply induced by starvation. Cell growth occurs strictly by elongation of
the rod, which maintains a constant diameter at all growth rates. This process
involves expansion of the cell wall, requiring intercalation of new peptidoglycan
and teichoic acid material, as well as controlled hydrolysis of existing wall
material. Actin-like MreB proteins are the key spatial regulators that
orchestrate the plethora of enzymes needed for cell elongation, many of which are
thought to assemble into functional complexes called elongasomes. Cell division
requires a switch in the orientation of cell wall synthesis and is organised by a
tubulin-like protein FtsZ. FtsZ forms a ring-like structure at the site of
impending division, which is specified by a range of mainly negative regulators.
There it recruits a set of dedicated division proteins to form a structure called
the divisome, which brings about the process of division. During sporulation,
both the positioning and fine structure of the division septum are altered, and
again, several dedicated proteins that contribute specifically to this process
have been identified. This chapter summarises our current understanding of
elongation and division in B. subtilis, with particular emphasis on the
cytoskeletal proteins MreB and FtsZ, and highlights where the major gaps in our
understanding remain.
PMID- 28500530
TI - Structure and Dynamics of Actin-Like Cytomotive Filaments in Plasmid Segregation.
AB - One of the well-known functions of the bacterial cytoskeleton is plasmid
segregation. Type II plasmid segregation systems, among the best characterized
with respect to the mechanism of action, possess an actin-like cytomotive
filament as the motor component. This chapter describes the essential components
of the plasmid segregation machinery and their mechanism of action, concentrating
on the actin-like protein family of the bacterial cytoskeleton. The structures of
the actin-like filaments depend on their nucleotide state and these in turn
contribute to the dynamics of the filaments. The components that link the
filaments to the plasmid DNA also regulate filament dynamics. The modulation of
the dynamics facilitates the cytomotive filament to function as a mitotic spindle
with a minimal number of components.
PMID- 28500531
TI - Tubulin-Like Proteins in Prokaryotic DNA Positioning.
AB - A family of tubulin-related proteins (TubZs) has been identified in prokaryotes
as being important for the inheritance of virulence plasmids of several
pathogenic Bacilli and also being implicated in the lysogenic life cycle of
several bacteriophages. Cell biological studies and reconstitution experiments
revealed that TubZs function as prokaryotic cytomotive filaments, providing one
dimensional motive forces. Plasmid-borne TubZ filaments most likely transport
plasmid centromeric complexes by depolymerisation, pulling on the plasmid DNA, in
vitro. In contrast, phage-borne TubZ (PhuZ) pushes bacteriophage particles
(virions) to mid cell by filament growth. Structural studies by both
crystallography and electron cryo-microscopy of multiple proteins, both from the
plasmid partitioning sub-group and the bacteriophage virion centring group of
TubZ homologues, allow a detailed consideration of the structural phylogeny of
the group as a whole, while complete structures of both crystallographic
protofilaments at high resolution and fully polymerised filaments at intermediate
resolution by cryo-EM have revealed details of the polymerisation behaviour of
both TubZ sub-groups.
PMID- 28500532
TI - The Structure, Function and Roles of the Archaeal ESCRT Apparatus.
AB - Although morphologically resembling bacteria, archaea constitute a distinct
domain of life with a closer affiliation to eukaryotes than to bacteria. This
similarity is seen in the machineries for a number of essential cellular
processes, including DNA replication and gene transcription. Perhaps
surprisingly, given their prokaryotic morphology, some archaea also possess a
core cell division apparatus that is related to that involved in the final stages
of membrane abscission in vertebrate cells, the ESCRT machinery.
PMID- 28500533
TI - Archaeal Actin-Family Filament Systems.
AB - Actin represents one of the most abundant and conserved eukaryotic proteins over
time, and has an important role in many different cellular processes such as cell
shape determination, motility, force generation, cytokinesis, amongst many
others. Eukaryotic actin has been studied for decades and was for a long time
considered a eukaryote-specific trait. However, in the early 2000s a bacterial
actin homolog, MreB, was identified, characterized and found to have a
cytoskeletal function and group within the superfamily of actin proteins. More
recently, an actin cytoskeleton was also identified in archaea. The genome of the
hyperthermophilic crenarchaeon Pyrobaculum calidifontis contains a five-gene
cluster named Arcade encoding for an actin homolog, Crenactin, polymerizing into
helical filaments spanning the whole length of the cell. Phylogenetic and
structural studies place Crenactin closer to the eukaryotic actin than to the
bacterial homologues. A significant difference, however, is that Crenactin can
form single helical filaments in addition to filaments containing two intertwined
proto filaments. The genome of the recently discovered Lokiarchaeota encodes
several different actin homologues, termed Lokiactins, which are even more
closely related to the eukaryotic actin than Crenactin. A primitive, dynamic
actin-based cytoskeleton in archaea could have enabled the engulfment of the
alphaproteobacterial progenitor of the mitochondria, a key-event in the evolution
of eukaryotes.
PMID- 28500534
TI - The Tubulin Superfamily in Archaea.
AB - In comparison with bacteria and eukaryotes, the large and diverse group of
microorganisms known as archaea possess a great diversity of cytoskeletal
proteins, including members of the tubulin superfamily. Many species contain
FtsZ, CetZ and even possible tubulins; however, some major taxonomic groups do
not contain any member of the tubulin superfamily. Studies using the model
archaeon, Halferax volcanii have recently been instrumental in defining the
fundamental roles of FtsZ and CetZ in archaeal cell division and cell shape
regulation. Structural studies of archaeal tubulin superfamily proteins provide a
definitive contribution to the cytoskeletal field, showing which protein-types
must have developed prior to the divergence of archaea and eukaryotes. Several
regions of the globular core domain - the "signature" motifs - combine in the 3D
structure of the common molecular fold to form the GTP-binding site. They are the
most conserved sequence elements and provide the primary basis for identification
of new superfamily members through homology searches. The currently well
characterised proteins also all share a common mechanism of GTP-dependent
polymerisation, in which GTP molecules are sandwiched between successive subunits
that are arranged in a head-to-tail manner. However, some poorly-characterised
archaeal protein families retain only some of the signature motifs and are
unlikely to be capable of dynamic polymerisation, since the promotion of
depolymerisation by hydrolysis to GDP depends on contributions from both subunits
that sandwich the nucleotide in the polymer.
PMID- 28500535
TI - Reconstitution of Protein Dynamics Involved in Bacterial Cell Division.
AB - Even simple cells like bacteria have precisely regulated cellular anatomies,
which allow them to grow, divide and to respond to internal or external cues with
high fidelity. How spatial and temporal intracellular organization in prokaryotic
cells is achieved and maintained on the basis of locally interacting proteins
still remains largely a mystery. Bulk biochemical assays with purified components
and in vivo experiments help us to approach key cellular processes from two
opposite ends, in terms of minimal and maximal complexity. However, to understand
how cellular phenomena emerge, that are more than the sum of their parts, we have
to assemble cellular subsystems step by step from the bottom up. Here, we review
recent in vitro reconstitution experiments with proteins of the bacterial cell
division machinery and illustrate how they help to shed light on fundamental
cellular mechanisms that constitute spatiotemporal order and regulate cell
division.
PMID- 28500536
TI - Benzocoumarin-Styryl Hybrids: Aggregation and Viscosity Induced Emission
Enhancement.
AB - Two benzo[h]chromen-3-yl)ethylidene) malononitrile styryl hybrid dyes are
synthesized and characterized by NMR and elemental analysis. One is based on
nitrogen donor and other on oxygen (3b and 3b respectively). Dyes are low
emissive in the solution but dramatically showed increase in emission intensity
in aggregates form in the THF (tetrahydrofuran) /water system. Dyes are also
sensitive to viscosity and showed increased emission intensity in the DCM:PEG 400
system and DMF:PEG 400 system respectively. Dyes 3a and 3b showed higher
viscosity sensitivity constant (0.67 and 0.39 respectively) in DMF:PEG 400 system
compared to DCM:PEG 400 (0.47 and 0.21 respectively) system which is contrary to
the traditional concept of FMRs. Results shows that lowering of twisted
intramolecular charge transfer (TICT) and increase in intramolecular charge
transfer (ICT) in the excited state could be the reason for such behavior in the
aggregate and highly viscous state. This study may provide the new insights into
the field of AIEE and FMR research of such hybrid molecules.
PMID- 28500537
TI - Zhongxian Lin: Founder of color psychology in China.
PMID- 28500538
TI - Lian-Cang Xu: the founder of management psychology in China.
PMID- 28500539
TI - Hybrid PET/CT and PET/MRI imaging of vulnerable coronary plaque and myocardial
scar tissue in acute myocardial infarction.
AB - BACKGROUND: Following an acute coronary syndrome, combined CT and PET with 18F
NaF can identify coronary atherosclerotic plaques that have ruptured or eroded.
However, the processes behind 18F-NaF uptake in vulnerable plaques remain
unclear. METHODS AND RESULTS: Ten patients with STEMI were scanned after 18F-NaF
injection, for 75 minutes in a Siemens PET/MR scanner using delayed enhancement
(LGE). They were then scanned in a Siemens PET/CT scanner for 10 minutes. Tissue
to-background ratio (TBR) was compared between the culprit lesion in the IRA and
remote non-culprit lesions in an effort to independently validate prior studies.
Additionally, we performed a proof-of-principle study comparing TBR in scar
tissue and remote myocardium using LGE images and PET/MR or PET/CT data. From the
33 coronary lesions detected on PET/CT, TBRs for culprit lesions were higher than
for non-culprit lesions (TBR = 2.11 +/- 0.45 vs 1.46 +/- 0.48; P < 0.001).
Interestingly, the TBR measured on the PET/CT was higher for infarcted myocardium
than for remote myocardium (TBR = 0.81 +/- 0.10 vs 0.71 +/- 0.05; P = 0.003).
These results were confirmed using the PET/MR data (TBR = 0.81 +/- 0.10 for scar,
TBR = 0.71 +/- 0.06 for healthy myocardium, P = 0.03). CONCLUSIONS: We confirmed
the potential of 18F-NaF PET/CT imaging to detect vulnerable coronary lesions.
Moreover, we demonstrated proof-of-principle that 18F-NaF concurrently detects
myocardial scar tissue.
PMID- 28500540
TI - Prediction of sudden cardiac death in patients with chronic heart failure by
regional washout rate in cardiac MIBG SPECT imaging.
AB - BACKGROUND: The sympathetic nervous system provides an important trigger for
major arrhythmic events through regional heterogeneity of sympathetic activity,
which could be evaluated by SPECT imaging as the regional MIBG washout rate (WR).
There is little information available on the prognostic value of regional WR in
SPECT imaging for the prediction of sudden cardiac death (SCD) in patients with
chronic heart failure (CHF). METHODS: We studied 73 CHF outpatients with LVEF <
40%. At study entry, the regional WR was measured in 17 segments on the polar
map. We defined abnormal regional WR as both the regional WR range (maximum -
minimum regional WR) and maximum regional WR > mean value + 2SD obtained in 15
normal controls. RESULTS: During a mean follow-up of 7.5 +/- 4.1 years, 15 of 73
patients had SCD. The abnormal regional WR and abnormal global WR on planar
images were significantly and independently associated with SCD. Patients with
both the abnormal regional WR and global WR had a significantly higher risk of
SCD than those with none of these criteria. CONCLUSIONS: The analysis of regional
MIBG WR on SPECT imaging provides additional prognostic value to global WR on
planar images for SCD prediction in CHF patients.
PMID- 28500541
TI - Ambivalence over emotional expression, intrusive thoughts, and posttraumatic
stress symptoms among Chinese American breast cancer survivors.
AB - OBJECTIVE: Posttraumatic stress symptoms (PTSS) are common among breast cancer
survivors. However, the association and the underlying mediating mechanism
between psychosocial factors and PTSS were rarely investigated among breast
cancer survivors. Previous studies have suggested the importance of emotional
expression in cancer survivors' PTSS. This study examined the association between
ambivalence over emotional expression (AEE; defined as the conflict between the
desire to express feelings and the fear of its consequences) and PTSS, and
proposed intrusive thoughts as the mediators in such an association. We tested
this proposed mediation model among Chinese breast cancer survivors whose culture
discourages emotional expression. METHODS: Participants were 118 Chinese-speaking
breast cancer survivors in the USA, who were diagnosed with breast cancer of
stages 0-III within the past 5 years. They completed questionnaires measuring
their levels of AEE, PTSS, and intrusive thoughts. RESULTS: AEE was positively
associated with intrusive thoughts (r = 0.43, p < 01), which were positively
associated with the arousal and avoidance subscales of PTSS (r = 0.68 and r =
0.62, respectively, p < .01). Path analysis supported a partial mediation model
with an indirect effect from AEE to the latent variable of PTSS (with both
arousal and avoidance as indicators) via intrusive thoughts (beta = 0.29; 95% CI=
0.18, 0.42) and the direct effect from AEE to the latent variable of PTSS (beta =
0.21, 95% CI = 0.07, 0.35), all p < .001. CONCLUSIONS: Those who are highly
ambivalent about emotion expression tend to have higher PTSS, and this may be
partially due to the lack of opportunities to discuss emotional events, thereby
increasing the repetitive cancer-related negative thoughts. Intervention for PTSS
should consider helping cancer patients to develop adaptive emotional regulation
strategies to reduce the detrimental effects of cancer-related intrusive
thoughts.
PMID- 28500542
TI - Self-report of symptoms in children with cancer younger than 8 years of age: a
systematic review.
AB - OBJECTIVE: The study's objective was to summarize the psychometric evaluation of
self-report symptom instruments used in children with cancer younger than 8 years
of age. METHODS: We conducted electronic searches of Ovid Medline, EMBASE,
PsycInfo, Science Citation, Social Science Citation (Web of Science), and CINAHL.
We included studies of children with cancer in which their self-report symptoms
had been quantified and in which results were described for those younger than 8
years of age. The search was restricted to publications in English. Two reviewers
screened studies and abstracted all data in duplicate. Descriptive analysis of
reliability and validity was performed. RESULTS: Thirteen studies were included.
Only one study recruited children <8 years alone. Most studies described
reliability and validity in a wider age range cohort in which most children were
older than 8 years of age. Of the eight studies that evaluated reliability within
the younger age group, six raised concerns about poor internal consistency with
Cronbach's alpha <0.7 in at least one dimension. Concerns about test re-test
reliability and inter-rater reliability were also observed. None of the studies
evaluated validity. CONCLUSIONS: We failed to demonstrate that currently
available instruments to measure self-report symptoms are reliable or valid
specifically for children with cancer younger than 8 years of age. Development of
psychometrically robust instruments for younger children should be a priority.
PMID- 28500543
TI - Impact of spin label rigidity on extent and accuracy of distance information from
PRE data.
AB - Paramagnetic relaxation enhancement (PRE) is a versatile tool for NMR
spectroscopic structural and kinetic studies in biological macromolecules. Here,
we compare the quality of PRE data derived from two spin labels with markedly
different dynamic properties for large RNAs using the I-A riboswitch aptamer
domain (78 nt) from Mesoplamsa florum as model system. We designed two I-A
aptamer constructs that were spin-labeled by noncovalent hybridization of short
spin-labeled oligomer fragments. As an example of a flexible spin label, UreidoU
TEMPO was incorporated into the 3' terminal end of helix P1 while, the recently
developed rigid spin-label Cm was incorporated in the 5' terminal end of helix
P1. We determined PRE rates obtained from aromatic 13C bound proton intensities
and compared these rates to PREs derived from imino proton intensities in this
sizeable RNA (~78 nt). PRE restraints derived from both imino and aromatic
protons yielded similar data quality, and hence can both be reliably used for PRE
determination. For NMR, the data quality derived from the rigid spin label Cm is
slightly better than the data quality for the flexible UreidoTEMPO as judged by
comparison of the structural agreement with the I-A aptamer crystal structure
(3SKI).
PMID- 28500545
TI - Nocardia tengchongensis sp. nov., isolated from a soil sample.
AB - The taxonomic status was determined of two actinomycetes, designated CFH S0057T
and CFH S0065, that were isolated from soil samples collected from an extinct
volcano in Tengchong county, Yunnan province, south-west China. Phylogenetic
analysis based on 16S rRNA gene sequences showed that strains CFH S0057T and CFH
S0065 belong to the genus Nocardia and formed a single clade within this genus.
The two isolates were able to grow at 4-45 degrees C, pH 5.0-7.0 and with a NaCl
tolerance up to 5.0% (w/v). The whole-cell hydrolysates were rich in meso
diaminopimelic acid, galactose, arabinose and fructose. Mycolic acids were
present. Strains CFH S0057T and CFH S0065 exhibited a menaquinone system with MK
8 (H4, omega cyclo), and the major polar lipids consisted of
diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol,
phosphatidylinositol mannoside and one unidentified phospholipid. Major fatty
acids were C16:0, Summed features 3, C18:1 omega9c and C18:0 10-methyl (TBSA).
The genomic DNA G + C contents of strains CFH S0057T and CFH S0065 were 65.7 and
66.1 mol%, respectively. The combined genotypic, phenotypic and chemotaxonomic
results indicated the isolates are considered to represent a novel species of the
genus Nocardia, for which the name Nocardia tengchongensis sp. nov. is proposed.
The type strain is CFH S0057T (= KCTC 29485T = JCM 30083T).
PMID- 28500544
TI - Diversity and plant growth promoting properties of rhizobia isolated from root
nodules of Ononis arvensis.
AB - This is the first report describing isolates from root nodules of Ononis arvensis
(field restharrow). The aim of this investigation was to describe the diversity,
phylogeny, and plant growth promoting features of microsymbionts of O. arvensis,
i.e., a legume plant growing in different places of the southern part of Poland.
Twenty-nine bacterial isolates were characterized in terms of their phenotypic
properties, genome fingerprinting, and comparative analysis of their 16S rRNA,
nodC and acdS gene sequences. Based on the nodC and 16S rRNA gene phylogenies,
the O. arvensis symbionts were grouped close to bacteria of the genera Rhizobium
and Mesorhizobium, which formed monophyletic clusters. The acdS gene sequences of
all the isolates tested exhibited the highest similarities to the corresponding
gene sequences of genus Mesorhizobium strains. The presence of the acdS genes in
the genomes of rhizobia specific for O. arvensis implies that these bacteria may
promote the growth and development of their host plant in stress conditions. The
isolated bacteria showed a high genomic diversity and, in the BOX-PCR reaction,
all of them (except three) exhibited DNA fingerprints specific only for them. Our
studies showed that restharrow isolates formed effective symbiotic interactions
with their native host (O. arvensis) and Ononis spinosa but not with Trifolium
repens and Medicago sativa belonging to the same tribe Trifolieae as Ononis
species and not with Lotus corniculatus, representing the tribe Loteae.
PMID- 28500547
TI - Effects of Se on the growth, tolerance, and antioxidative systems of three
alfalfa cultivars.
AB - The aim of this study was to evaluate the selenium (Se) tolerance and exploit the
physiological mechanisms in roots, stem, and leaves of three alfalfa cultivars to
different concentrations of Se for 60 days. Among three cultivars, Medicago
sativa ssp. displayed the highest Se concentrations in tissues, the largest Se
amount in aerial parts, the highest bioconcentration factor (BCF) in aerial
parts, and translocation factor (TF) under Se stress. Under Se stress, induced
O2*- production in roots and leaves and increases in free proline and activities
of antioxidative enzymes were observed in M. sativa ssp. Based on the above
results, it is concluded that M. sativa ssp. is superior to the other two
cultivars for Se phytoremediation, and its well-coordinated physiological changes
under Se stress confer the great Se tolerance of this cultivar.
PMID- 28500546
TI - Quantitative image analysis of polyhydroxyalkanoates inclusions from microbial
mixed cultures under different SBR operation strategies.
AB - Polyhydroxyalkanoates (PHAs) produced from mixed microbial cultures (MMC),
regarded as potential substitutes of petrochemical plastics, can be found as
intracellular granules in various microorganisms under limited nutrient
conditions and excess of carbon source. PHA is traditionally quantified by
laborious and time-consuming chromatography analysis, and a simpler and faster
method to assess PHA contents from MMC, such as quantitative image analysis
(QIA), is of great interest. The main purpose of the present work was to upgrade
a previously developed QIA methodology (as reported by Mesquita et al. (Anal Chim
Acta 770:36-44, 2013a, Anal Chim Acta 865:8-15, 2015)) for MMC intracellular PHA
contents quantification, increase the studied intracellular PHA concentration
range, and extend to different sequencing batch reactor (SBR) operation
strategies. Therefore, the operation of a new aerobic dynamic feeding (ADF) SBR
allowed further extending the studied operating conditions, dataset, and range of
the MMC intracellular PHA contents from the previously reported anaerobic/aerobic
cycle SBR. Nile Blue A (NBA) staining was employed for epifluorescence microscope
visualization and image acquisition, further fed to a custom developed QIA. Data
from each of the feast and famine cycles of both SBR were individually processed
using chemometrics analysis, obtaining the correspondent partial least squares
(PLS) models. The PHA concentrations determined from PLS models were further
plotted against the results obtained in the standard chromatographic method. For
both SBR, the predicted ability was higher at the end of the feast stage than for
the famine stage. Indeed, an independent feast and famine QIA data treatment was
found to be fundamental to obtain the best prediction abilities. Furthermore, a
promising overall correlation (R 2 of 0.83) could be found combining the overall
QIA data regarding the PHA prediction up to a concentration of 1785.1 mg L-1
(37.3 wt%). Thus, the results confirm that the presented QIA methodology can be
seen as promising for estimating higher intracellular PHA concentrations for a
larger reactors operation systems and further extending the prediction range of
previous studies.
PMID- 28500549
TI - Adsorption affinity and selectivity of 3-ureidopropyltriethoxysilane grafted oil
palm empty fruit bunches towards mercury ions.
AB - This study was conducted to investigate the potential application of oil palm
empty fruit branches (OPEFB) as adsorbents to remove organic methylmercurry,
MeHg(II), and inorganic Hg(II) from aqueous solution. The OPEFB was
functionalized with amine containing ligand namely 3-ureidopropyltriethoxysilane
(UPTES) aiming for better adsorption performance towards both mercury ions. The
adsorption was found to be dependent on initial pH, initial concentraton,
temperatures, and contact time. The maximum adsorption capacities (Qm.exp) of
Hg(II) adsorption onto OPEFB and UPTES-OPEFB were 0.226 and 0.773 mmol/g,
respectively. The Qm.exp of MeHg(II) onto OPEFB, however, was higher than UPTES
OPEFB. The adsorption kinetic data obeyed the Elovich model and the adsorption
was controlled by the film-diffusion step. The calculated thermodynamic
parameters indicate an endothermic adsorption process. Adsorption data analysis
indicates that the adsorption mechanism may include ion-exchange, complexation,
and physisorption interactions. The potential applications of adsorbents were
demonstrated using oilfield produced water and natural gas condensate. The UPTES
OPEFB offered higher selectivity towards both mercury ions than OPEFB. The
regenerability studies indicated that the adsorbent could be reused for multiple
cycles.
PMID- 28500548
TI - Decontamination of arsenic(V)-contained liquid phase utilizing Fe3O4/bone char
nanocomposite encapsulated in chitosan biopolymer.
AB - The application of a novel nanocomposite synthesized through the combination of
Fe3O4 nanoparticles and bone char particles for the adsorption of As(V) ions in
the aquatic medium was investigated. As-prepared nanocomposite was immobilized by
using chitosan biopolymer. The characterization of the nanocomposite was
performed via SEM, XRD, FT-IR, and BET together with the determination of zero
point charge of the adsorbent surface. As results, the obtained experimental data
were fitted well with pseudo-first-order kinetic model (R2 = 0.997) and Langmuir
isotherm model (R2 = 0.990) with the maximum adsorption capacity of about 112
MUg/g. Increasing the dosage of nanocomposite and initial solute concentration
led to increasing the adsorption capacity of As(V) ions, while decreasing the
solution temperature resulted in the enhanced adsorption process. According to
the results of thermodynamic study, the adsorption of As(V) ions onto the
nanocomposite was spontaneous and exothermic in nature.
PMID- 28500550
TI - Reclamation of heavy metals from contaminated soil using organic acid liquid
generated from food waste: removal of Cd, Cu, and Zn, and soil fertility
improvement.
AB - Food waste fermentation generates complicated organic and acidic liquids with low
pH. In this work, it was found that an organic acid liquid with pH 3.28 and
volatile low-molecular-weight organic acid (VLMWOA) content of 5.2 g/L could be
produced from food wastes after 9-day fermentation. When the liquid-to-solid
ratio was 50:1, temperature was 40 degrees C, and contact time was 0.5-1 day,
92.9, 78.8, and 52.2% of the Cd, Cu, and Zn in the contaminated soil could be
washed out using the fermented food waste liquid, respectively. The water
soluble, acid-soluble, and partly reducible heavy metal fractions can be removed
after 0.5-day contact time, which was more effective than that using commercially
available VLMWOAs (29-72% removal), as the former contained microorganisms and
adequate amounts of nutrients (nitrogen, phosphorous, and exchangeable Na, K, and
Ca) which favored the washing process of heavy metals. It is thus suggested that
the organic acid fractions from food waste has a considerable potential for
reclaiming contaminated soil while improving soil fertility.
PMID- 28500551
TI - Effect of industrial and domestic ash from biomass combustion, and spent coffee
grounds, on soil fertility and plant growth: experiments at field conditions.
AB - An experimental study was conducted at field conditions in order to evaluate the
effect of application of ash from biomass combustion on some soil fertility
characteristics and plant growth. Application of 7.5 Mg ha-1 industrial fly ash
(IA), domestic ash (DA), and a 50:50 mix of domestic ash (DA) and spent coffee
grounds (SCG) was made in different soil parcels. Lolium perenne seeds were sown
and the grown biomass was harvested and quantified after 60 days. Soil samples
from each parcel were also collected after that period and characterized. Both
soil and grown biomass samples were analyzed for Ca, Mg, Na, K, P, Fe, Mn, Zn,
and Al contents. Soil pH was determined before and after amendment. All
applications rose significantly soil pH. Domestic ash, whether combined with
coffee grounds or not, proved to be efficient at supplying available
macronutrients Ca, Mg, K, and P to the soil and also reducing availability of Al
(more than industrial ash). However, it inhibited plant growth, even more when
combined with spent coffee grounds. As regards to elemental abundance in plant
tissue, both domestic ash treatments reduced Ca and enhanced Al contents, unlike
industrial ash, which proved less harmful for the load applied in the soil.
Hence, it was possible to conclude that application load should be a limiting
factor for this management option for the studied materials.
PMID- 28500552
TI - Adsorption of terpenic compounds onto organo-palygorskite.
AB - Essential oils from aromatic plants are currently mentioned as suitable tools for
excellent protection of stored grains from insect pest attacks. The present work
aimed to study the processes of the synthesis insecticidal formulation with clay.
The active terpenic compounds of essential oil of Eucalyptus globulus (Eg) were
fixed in the palygorskite by adsorption process. Two sample types of
palygorskites were used: raw and organo-palygorskite. The palygorskite clays were
characterized by different physicochemical techniques including X-ray diffraction
(XRD), Fourier transform infrared (FTIR) analyses, thermogravimetric analysis
(TG), differential thermal analysis (DTA), Brunauer-Emmet-Teller (BET), and
scanning electron microscope (SEM). Results reveal that the raw clay has a
fibrous structure with impurities essential calcite. These structures and
physicochemical properties of raw palygorskite and organo-palygorskite give it
the potential of material adsorbent. Results show that the adsorption capacity
strongly depends on affinity between terpenic compounds and organic cations
rather than on interlayer distance of organo-palygorskite. The highest adsorption
capacity of terpenic compounds is acquired with palygorskite interlaced by
didodecyldimethylammonium bromide (DDDMA). These results validated the potential
utility of the Paly-DDDMA as adsorbent fibrous clay for the retention of terpenic
compounds in application of environmental preservation.
PMID- 28500553
TI - Characterization of rainwater chemical composition after a Southeast Asia haze
event: insight of transboundary pollutant transport during the northeast monsoon.
AB - Open biomass burning in Peninsula Malaysia, Sumatra, and parts of the Indochinese
region is a major source of transboundary haze pollution in the Southeast Asia.
To study the influence of haze on rainwater chemistry, a short-term investigation
was carried out during the occurrence of a severe haze episode from March to
April 2014. Rainwater samples were collected after a prolonged drought and
analyzed for heavy metals and major ion concentrations using inductively coupled
plasma mass spectroscopy (ICP-MS) and ion chromatography (IC), respectively. The
chemical composition and morphology of the solid particulates suspended in
rainwater were examined using a scanning electron microscope coupled with energy
dispersive X-ray spectroscopy (SEM-EDS). The dataset was further interpreted
using enrichment factors (EF), statistical analysis, and a back trajectory (BT)
model to find the possible sources of the particulates and pollutants. The
results show a drop in rainwater pH from near neutral (pH 6.54) to acidic ( 43.0, p <
0.001), with increased visibility. However, the median CD between the white patch
and surrounding mucosa decreased after NBI (44.8 -> 30.3, p < 0.001). The fibrin
cap was paler than the white patch of candidiasis, but the increased visibility
of the fibrin cap by NBI enabled it to be found more easily. This is the first
report of a case in which NBI was helpful in locating a fibrin cap of EVs.
PMID- 28500574
TI - Tissue Engineering-Bridging the Gap.
PMID- 28500571
TI - Associations between illness duration and health-related quality of life in
specified mental and physical chronic health conditions: results from a
population-based survey.
AB - PURPOSE: We compared health-related quality of life (HRQOL) in incident (<=1 year
since diagnosis), mid-term (>1-5 years since diagnosis), and long-term (>5 years
since diagnosis) cases of mental and physical chronic illness with the general
population and assessed the modifying effects of age and gender on the
association between HRQOL and illness duration. METHODS: Data from the 2007
Australian National Health and Mental Wellbeing Survey were used. HRQOL was
captured by the Assessment of Quality of Life Scale 4D. Multivariable linear
regression analyses compared HRQOL of individuals with different duration of
illnesses with those who did not have the condition of interest. RESULTS: The
8841 survey respondents were aged 16-85 years (median 43 years, 50.3% female).
For the overall sample, worse HRQOL was associated with incident (P = 0.049) and
mid-term (P = 0.036) stroke and long-term depression (P < 0.001) and anxiety (P =
0.001). Age had moderating effect on the associations between HRQOL and duration
of asthma (P < 0.001), arthritis (P = 0.001), diabetes (P = 0.004), stroke (P =
0.009), depression (P < 0.001), bipolar disorder (P < 0.001), and anxiety (P <
0.001), but not heart disease (P = 0.102). In older ages, the greatest loss in
HRQOL was associated with incident asthma, depression, and bipolar disorder. In
younger ages, the greatest loss in HRQOL was associated with arthritis (any
duration) and incident diabetes and anxiety. Additionally, gender moderated the
association between HRQOL and arthritis, with worse HRQOL among men with incident
arthritis (P = 0.047). CONCLUSIONS: Loss of HRQOL associated with longer duration
of chronic illness is most apparent in stroke and mental illness and differs
between age groups.
PMID- 28500572
TI - Methods and impact of engagement in research, from theory to practice and back
again: early findings from the Patient-Centered Outcomes Research Institute.
AB - PURPOSE: Since 2012, PCORI has been funding patient-centered comparative
effectiveness research with a requirement for engaging patients and other
stakeholders in the research, a requirement that is unique among the US funders
of clinical research. This paper presents PCORI's evaluation framework for
assessing the short- and long-term impacts of engagement; describes engagement in
PCORI projects (types of stakeholders engaged, when in the research process they
are engaged and how they are engaged, contributions of their engagement); and
identifies the effects of engagement on study design, processes, and outcomes
selection, as reported by both PCORI-funded investigators and patient and other
stakeholder research partners. METHODS: Detailed quantitative and qualitative
information collected annually from investigators and their partners was analyzed
via descriptive statistics and cross-sectional qualitative content and thematic
analysis, and compared against the outcomes expected from the evaluation
framework and its underlying conceptual model. RESULTS: The data support the role
of engaged research partners in refinements to the research questions, selection
of interventions to compare, choice of study outcomes and how they are measured,
contributions to strategies for recruitment, and ensuring studies are patient
centered. CONCLUSIONS: The evaluation framework and the underlying conceptual
model are supported by results to date. PCORI will continue to assess the effects
of engagement as the funded projects progress toward completion, dissemination,
and uptake into clinical decision making.
PMID- 28500575
TI - Salt and Blood Pressure: Cutting Through the Scientific Fog.
PMID- 28500573
TI - Brief Report: Contrasting Profiles of Everyday Executive Functioning in Smith
Magenis Syndrome and Down Syndrome.
AB - Everyday executive function (EF) was examined in Smith-Magenis syndrome (SMS),
associated with high risk of behaviour disorder, and Down syndrome (DS),
associated with relatively low risk of behaviour disorder. Caregivers of 13
children with SMS and 17 with DS rated everyday EF using the Behavioral Rating
Inventory of Executive Functioning-Preschool. Greater everyday EF deficits
relative to adaptive ability were evident in SMS than in DS. The SMS profile of
everyday EF abilities was relatively uniform; in DS emotional control strengths
and working memory weaknesses were evident. Findings implicate broad everyday EF
difficulties in SMS compared to DS, corresponding with increased rates of
behaviour disorder in SMS. Findings further suggest that everyday EF profiles
may, in part, be syndrome related.
PMID- 28500576
TI - 66th Annual Scientific Sessions of the American College of Cardiology: 17-19
March 2017; Washington, DC, USA.
PMID- 28500577
TI - Pectin Esterification Degree in the Bioavailability of Non-heme Iron in Women.
AB - Pectins are a type of soluble fiber present in natural and processed foods.
Evidence regarding the effect of esterification degree of pectins on iron
absorption in humans is scarce. In the present study, the effect of pectins with
different degrees of esterification on non-heme iron absorption in women was
evaluated. A controlled experimental study was conducted with block design,
involving 13 apparently healthy, adult women. Each subject received 5 mg Fe
(FeSO4) without pectin (control) or accompanied by 5 g citrus pectin, two with a
low degree of esterification (27 and 36%), and one with a high degree of
esterification (67 to 73%), each on different days. Each day, the 5 mg Fe doses
were marked with radioactive 59Fe or 55Fe. Radioactivity incorporated into
erythrocytes was determined in blood samples 14 days after the marked Fe doses
were consumed. On days 18 and 36 of study, 30 and 20 mL blood samples were
obtained, respectively, and blood sample radioactivity incorporated into
erythrocytes was determined. Body iron status was determined from blood taken on
day 18. Whole body blood volume was estimated for calculate iron bioavailability;
it was assumed that 80% of absorbed radioactivity was incorporated into the Hb.
All women participants signed an informed consent of participation at baseline.
Iron bioavailability (mean geometric +/-1 SD) alone (control) was 18.2% (12.3
27.1%), iron + pectin27 was 17.2% (10.2-29.2%), iron + pectin36 was 15.3% (9.5
24.6%), and iron + pectin67 was 19.5% (10.0-38.0%). No statistically significant
differences between iron bioavailability (repeated measures ANOVA, p = 0.22) were
observed. Pectin esterification degree does not influence the bioavailability of
non-heme iron in women.
PMID- 28500578
TI - The Relationship Between Copper, Iron, and Selenium Levels and Alzheimer Disease.
AB - This study aimed to evaluate the concentrations of copper, iron, and selenium in
elderly people with Alzheimer disease (AD), comparing the same parameters in a
paired group of healthy people, in order to verify if the amount of these metals
may influence the cognitive impairment progression. Patients' cognitive
impairment was evaluated by Clinical Dementia Rating (CDR). The elementary
quantification of erythrocytes was performed by inductively coupled plasma mass
spectrometry technique. The statistical analyses were carried out by SPSS
software 20.0 version, employing Shapiro-Wilk, Wilcoxon, Kruskall-Wallis, and
Spearman correlation tests, considering significant results of p < 0.05. The
sample was composed of 34% (n = 11) of women and 66% (n = 21) of men in each
group. The AD group was characterized by a higher concentration of copper (p <
0.0001) and iron (p < 0.0001); however, there is no significant difference in
selenium level. The analyses of the metal levels in different stages of AD were
not significant in CDR-1, however in CDR-2 and CDR-3, elevated levels of copper
and iron were observed; in CDR-3 patients, the level of selenium was lower (p <
0.008) compared to that of healthy controls. Patients with Alzheimer disease
studied present increase in biometal blood levels, especially of copper and iron,
and such increase can be different according to the disease stage and can cause
more impairment cognitive functions in AD.
PMID- 28500581
TI - John M. Hayes (1940-2017).
AB - ?.
PMID- 28500579
TI - Robotic repair of a right-sided Bochdalek hernia: a case report and literature
review.
AB - BACKGROUND: Bochdalek hernias (BHs) are usually diagnosed in the neonatal period,
occurring in 1/2200-1/12,500 live births. There are few reported cases of BHs in
adults. Robotic repair has not been described in current literature as opposed to
the laparoscopic approach. Here we present a case of an adult with clinical signs
of bowel obstruction secondary to a BH which was repaired using a robotic
approach. CASE REPORT: A 74-year-old gentleman with past medical history of
benign prostatic hyperplasia presented to the emergency department with a 1-week
history of nausea, vomiting, diarrhea, and decline in appetite. Computed
tomography (CT) imaging of the chest and abdomen revealed elevation of the right
hemidiaphragm and evidence of small bowel obstruction. The patient was managed
conservatively with nasogastric tube placement and bowel rest. He underwent
colonoscopy which could not be completed secondary to a transverse colon
stricture which was confirmed by barium enema. Upon repeat CT imaging, the
patient was found to have herniated colon through a right-sided diaphragmatic
hernia which caused colonic narrowing. The patient's intestinal obstruction
improved clinically with continued conservative management and he underwent
robotic repair of a right posterior diaphragmatic hernia. The hernia defect was
closed with interrupted figure of eight Ethibond sutures. A right-sided chest
tube was placed. Intraoperatively, the herniated proximal transverse colon was
noted to be ischemic and a right hemicolectomy was performed. He recovered well
and was discharged home on postoperative day 5. CONCLUSION: Congenital
diaphragmatic hernias usually present in the neonatal period and are rare in
adults. Operative repair is recommended and laparoscopic repair has been
described. Based on the existing literature regarding laparoscopic repair and the
current case report, robotic repair also appears to be a viable and safe option.
PMID- 28500580
TI - Is right colectomy a complete learning procedure for a robotic surgical program?
AB - This study analyses the utility of right colectomy as a learning procedure at the
beginning of a robotic surgical program. The hypothesis is that right colectomy
contains all the technical steps necessary to acquire basic abilities in robotics
surgery. The first 23 consecutive robotic right colectomy performed at the
beginning of a robotic program were analysed. All surgical times were recorded in
the operating room and second checked on a dedicated video-database. Specific
robotic times were analysed using CUSUM method to evaluate the learning curve.
CUSUM-derived learning phases were compared. Fourteen males and nine females with
a mean age of 68.7 (46-84) underwent robotic right colectomy. The mean overall
time was 265.3 min (180-320 min), docking time was 7 min (5-12 min), console time
was 205.9 min (145-260 min), and anastomotic time was 43.6 (25-60 min). CUSUM
analyses identified two learning phases: "starting phase" and "consolidation
phase". Interphase comparison confirmed the significant (p < 0.05) differences
between the two phases. Robotic technology facilitates the training process in
minimally invasive colorectal surgery. At the beginning of the learning curve,
right colectomy could represent a complete procedure to be proficient in robotic
colorectal surgery.
PMID- 28500582
TI - How Hot are Your Ions Really? A Threshold Collision-Induced Dissociation Study of
Substituted Benzylpyridinium "Thermometer" Ions.
AB - The first absolute experimental bond dissociation energies (BDEs) for the main
heterolytic bond cleavages of four benzylpyridinium "thermometer" ions are
measured using threshold collision-induced dissociation in a guided ion beam
tandem mass spectrometer. In this experiment, substituted benzylpyridinium ions
are introduced into the apparatus using an electrospray ionization source,
thermalized, and collided with Xe at varied kinetic energies to determine
absolute cross-sections for these reactions. Various effects are accounted for,
including kinetic shifts, multiple collisions, and internal and kinetic energy
distributions. These experimentally measured 0 K BDEs are compared with
computationally predicted values at the B3LYP-GD3BJ, M06-GD3, and MP2(full)
levels of theory with a 6-311+G(2d,2p) basis set using vibrational frequencies
and geometries determined at the B3LYP/6-311+G(d,p) level. Additional
dissociation pathways are observed for nitrobenzylpyridinium experimentally and
investigated using these same levels of theory. Experimental BDEs are also
compared against values in the literature at the AM1, HF, B3LYP, B3P86, and
CCSD(T) levels of theory. Of the calculated values obtained in this work, the
MP2(full) level of theory with counterpoise corrections best reproduces the
experimental results, as do the similar literature CCSD(T) values. Lastly, the
survival yield method is used to determine the characteristic temperature (Tchar)
of the electrospray source prior to the thermalization region and to confirm
efficient thermalization. Graphical Abstract ?.
PMID- 28500583
TI - Laser-Induced Acoustic Desorption/Electron Ionization of Amino Acids and Small
Peptides.
AB - Laser-induced acoustic desorption (LIAD) allows for desorption of neutral
nonvolatile compounds independent of their volatility or thermal stability. Many
different ionization methods have been coupled with LIAD. Hence, this setup
provides a better control over the types of ions formed than other mass
spectrometry evaporation/ionization methods commonly used to characterize
biomolecules, such as ESI or MALDI. In this study, the utility of LIAD coupled
with electron ionization (EI) was tested for the analysis of common amino acids
with no derivatization. The results compared favorably with previously reported
EI mass spectra obtained using thermal desorption/EI. Further, LIAD/EI mass
spectra collected for hydrochloride salts of two amino acids were found to be
similar to those measured for the neutral amino acids with the exception of the
appearance of an HCl+? ion. However, the hydrochloride salt of arginine showed a
distinctly different LIAD/EI mass spectrum than the previously published
literature EI mass spectrum, likely due to its highly basic side chain that makes
a specific zwitterionic form particularly favorable. Finally, EI mass spectra
were measured for seven small peptides, including di-, tri-, and tetrapeptides.
These mass spectra show a variety of ion types. However, an type ions are
prevalent. Also, electron-induced dissociation (EID) of protonated peptides has
been reported to form primarily an type ions. In addition, the loss of small
neutral molecules and side-chain cleavages were observed that are reminiscent of
other high-energy fragmentation methods, such as EID. Finally, the isomeric
dipeptides LG and IG were found to produce drastically different EI mass spectra,
thus allowing differentiation of the leucine and isoleucine amino acids in these
dipeptides. Graphical Abstract ?.
PMID- 28500584
TI - Specific Interactions of Antitumor Metallocenes with Deoxydinucleoside
Monophosphates.
AB - Bent metallocenes Cp2MCl2 (M = Ti, V, Nb, Mo) are known to exhibit cytotoxic
activity against a variety of cancer types. Though the mechanism of action is not
fully understood yet, the accumulation of the metal ions in the nucleus points
towards DNA as one of the primary targets. A set of eight deoxydinucleoside
monophosphates was used to study the adduct yields with metallocenes and
cisplatin. The binding affinities are reflected by the relative intensities of
the adducts and were found to follow the order of Pt > V > Ti > Mo (no adducts
were detected with Nb). High-resolution tandem mass spectrometry was applied to
locate the binding patterns in the deoxydinucleoside monophosphates. Whereas
cisplatin binds to the soft nitrogen atoms in the purine nucleobases, the
metallocenes additionally interact with the hard phosphate oxygen, which is in
good agreement with the hard and soft (Lewis) acids and bases (HSAB) concept.
However, the binding specificities were found to be unique for each metallocene.
The hard Lewis acids titanium and vanadium predominantly bind to the deprotonated
phosphate oxygen, whereas molybdenum, an intermediate Lewis acid, preferentially
interacts with the nucleobases. Nucleobases comprise alternative binding sites
for titanium and vanadium, presumably oxygen atoms for the first and nitrogen
atoms for the latter. In summary, the intrinsic binding behavior of the different
metallodrugs is reflected by the gas-phase dissociation of the adducts.
Consequently, MS/MS can provide insights into therapeutically relevant
interactions between metallodrugs and their cellular targets. Graphical Abstract
?.
PMID- 28500586
TI - Evidence of Spontaneous Post-transplant HCV Eradication in Two Failed DAA
Treatments Awaiting Liver Transplantation.
PMID- 28500585
TI - Systematic review and meta-analysis of complications and mortality of veno-venous
extracorporeal membrane oxygenation for refractory acute respiratory distress
syndrome.
AB - Veno-venous extracorporeal membrane oxygenation (ECMO) for refractory acute
respiratory distress syndrome (ARDS) is a rapidly expanding technique. We
performed a systematic review and meta-analysis of the most recent literature to
analyse complications and hospital mortality associated with this technique.
Using the PRISMA guidelines for systematic reviews and meta-analysis, MEDLINE and
EMBASE were systematically searched for studies reporting complications and
hospital mortality of adult patients receiving veno-venous ECMO for severe and
refractory ARDS. Studies were screened for low bias risk and assessed for study
size effect. Meta-analytic pooled estimation of study variables was performed
using a weighted random effects model for study size. Models with potential
moderators were explored using random effects meta-regression. Twelve studies
fulfilled inclusion criteria, representing a population of 1042 patients with
refractory ARDS. Pooled mortality at hospital discharge was 37.7% (CI 95% = 31.8
44.1; I 2 = 74.2%). Adjusted mortality including one imputable missing study was
39.3% (CI 95% = 33.1-45.9). Meta-regression model combining patient age, year of
study realization, mechanical ventilation (MV) days and prone positioning before
veno-venous ECMO was associated with hospital mortality (p < 0.001; R 2 = 0.80).
Patient age (b = 0.053; p = 0.01) and maximum cannula size during treatment (b =
0.075; p = 0.008) were also independently associated with mortality. Studies
reporting H1N1 patients presented inferior hospital mortality (24.8 vs 40.6%; p =
0.027). Complication rate was 40.2% (CI 95% = 25.8-56.5), being bleeding the most
frequent 29.3% (CI 95% = 20.8-39.6). Mortality due to complications was 6.9% (CI
95% = 4.1-11.2). Mechanical complications were present in 10.9% of cases (CI 95%
= 4.7-23.5), being oxygenator failure the most prevalent (12.8%; CI 95% = 7.1
21.7). Despite initial severity, significant portion of patients treated with
veno-venous ECMO survive hospital discharge. Patient age, H1N1-ARDS and cannula
size are independently associated with hospital mortality. Combined effect of
patient age, year of study realization, MV days and prone positioning before veno
venous ECMO influence patient outcome, and although medical complications are
frequent, their impact on mortality is limited.
PMID- 28500587
TI - Insights into the Pathogenesis of Pancreatic Cystic Neoplasms.
AB - With the current epidemic of diagnosed pancreatic cystic neoplasms on the rise, a
substantial amount of work has been done to unravel their biology, thus leading
to implications on clinical decision making. Recent genetic profiling of resected
human specimens has identified alterations in signaling pathways involving KRAS
and GNAS signaling as early events in the pathogenesis of intraductal pancreatic
mucinous neoplasms. Progressively, mutations in genes such as TP53, SMAD4, RNF43,
and others are thought to characterize invasive and advanced lesions. The role of
inflammation in fueling the growth and transformation of these cysts has also
begun to be studied with greater interest. A number of promising clinical studies
have attempted to integrate these genetic insights into classifying these cysts
and treating patients. We have reviewed existing literature on similar lines
besides commenting on some useful animal models that recapitulate molecular and
phenotypic progression of these cysts.
PMID- 28500588
TI - Sun Should Not Rise and Set on a Case of Acute Intestinal Obstruction.
PMID- 28500589
TI - Prospective Analysis of Minor Adverse Events After Colon Polypectomy.
AB - BACKGROUND: The risks of minor adverse events (MAEs) such as abdominal pain and
bloating after colon polypectomy (CP) are less clearly documented than major
adverse events. However, these complications may cause significant discomfort
during the performance of normal activities. We aimed to estimate the incidence
of MAE, associated risk factors, and healthcare resource utilization after CP.
METHODS: Patients who underwent CP were prospectively enrolled in this study.
Trained nurses contacted patients by telephone at 7 and 30 days after the CP and
administered a standardized questionnaire to obtain information regarding the
development of complications. MAEs were defined as any discomfort the patient
experienced after CP excluding major bleeding, perforation, and post-polypectomy
coagulation syndrome. RESULTS: Among a total of 2716 patients, 2253 patients
completed the interview at 7 and 30 days. MAEs occurred in 263 patients (11.7%)
before day 7, among which the most common were abdominal pain (4.5%), rectal
bleeding (2.8%), and bloating (2.6%). Cumulative incidence of MAEs was in 267
patients (11.9%) at 30 days. On multivariate analysis, female sex (odds ratio
[OR] 2.24, 95% confidence interval [CI] 1.58-3.18) and use of meperidine (OR
1.54, 95% CI 1.04-2.27) were risk factors for the occurrence of MAEs. Two
patients (0.7%) required hospital admission, 117 patients (43.8%) were treated
medically in the outpatient clinic, and the majority at 148 patients (55.4%)
experienced resolution of symptoms after observation. CONCLUSIONS: The post-CP
MAE rate was as low as 11.8%. The MAEs occurred mainly in the first seven
postoperative days and resulted in little use of healthcare resources.
PMID- 28500590
TI - Autolysis of Pichia pastoris induced by cold.
AB - The production of recombinant biopharmaceutical proteins is a multi-billion
dollar market. Protein recovery represents a major part of the production costs.
Pichia pastoris is one of the microbial systems most used for the production of
heterologous proteins. The use of a cold-induced promoter to express lytic
enzymes in the yeast after the growth stage could reduce protein recovery costs.
This study shows that a cold-shock can be applied to induce lysis of the yeast
cells. A strain of P. pastoris was constructed in which the endogenous eng gene
encoding a putative endo-beta-1,3-glucanase was overexpressed using the cold
shock induced promoter of the cctalpha gene from Saccharomyces cerevisiae. In the
transgenic P. pastoris, the expression of eng increased 3.6-fold after chilling
the cells from 30 to 4 degrees C (cold-shock stage) followed by incubation for 6
h (eng expression stage). The culture was heated to 30 degrees C for 6 h (ENG
synthesis stage) and kept at 37 degrees C for 24 h (lysis stage). After this
procedure the cell morphology changed, spheroplasts were obtained and cellular
lysis was observed. Thus, a clone of P. pastoris was obtained, which undergoes
autolysis after a cold-shock.
PMID- 28500591
TI - A Brief Introduction into the Renin-Angiotensin-Aldosterone System: New and Old
Techniques.
AB - The renin-angiotensin-aldosterone system (RAAS) is a complex system of enzymes,
receptors, and peptides that help to control blood pressure and fluid
homeostasis. Techniques in studying the RAAS can be difficult due to such factors
as peptide/enzyme stability and receptor localization. This paper gives a brief
account of the different components of the RAAS and current methods in measuring
each component. There is also a discussion of different methods in measuring stem
and immune cells by flow cytometry, hypertension, atherosclerosis, oxidative
stress, energy balance, and other RAAS-activated phenotypes. While studies on the
RAAS have been performed for over 100 years, new techniques have allowed
scientists to come up with new insights into this system. These techniques are
detailed in this Methods in Molecular Biology Series and give students new to
studying the RAAS the proper controls and technical details needed to perform
each procedure.
PMID- 28500592
TI - A Color Segmentation-Based Method to Quantify Atherosclerotic Lesion Compositions
with Immunostaining.
AB - There is an increasing recognition that atherosclerotic lesion composition,
rather than size, is the determinant of acute events. Immunostaining is a
commonly used method to characterize atherosclerotic lesion compositions. Here,
we describe a color segmentation-based approach in HSI (hue, saturation, and
intensity) color mode, which minimizes subjectivity and produces accurate and
consistent quantifications of atherosclerotic lesion compositions.
PMID- 28500593
TI - Assessment of Protein Carbonylation and Protein Tyrosine Phosphatase (PTP)
Oxidation in Vascular Smooth Muscle Cells (VSMCs) Using Immunoblotting
Approaches.
AB - Post-translational modification of proteins, such as phosphorylation and
oxidation, plays a major role in cellular signaling by influencing protein
structure and function. In vascular cells, in addition to influencing
phosphorylation, angiotensin II (Ang II) induces oxidation of proteins, important
in redox signaling in the cardiovascular and renal systems. The present chapter
describes immunoblotting approaches to assess irreversible protein carbonylation
and protein tyrosine phosphatase (PTPs) oxidation status in the proteome of
vascular smooth muscle cells (VSMC).Protein carbonylation is generally measured
using the OxyBlotTM approach, whereby derivatization of protein carbonyl groups
(C = O) on oxidized amino acids by dinitrophenylhydrazine (DNPH) results in the
formation of a stable dinitrophenyl (DNP) hydrazone product. The samples are
analyzed by SDS-PAGE and a primary antibody raised against the DNP moiety is used
to determine levels of irreversible protein carbonylation in the sample by
immunoblotting.Oxidation of PTPs can be evaluated using a monoclonal antibody
against the "hyperoxidized" (SO3H) catalytic site of these enzymes. The described
methodology offers the ability to discriminate between irreversible (SO3H) and
reversible (SOH) PTP oxidation states. Initially, the free unmodified PTP-thiols
(S-) are alkylated and the sample is split into two. One part is used to assess
the PTP-SO3H form. In the other part reversibly modified PTP-thiols are first
reduced and then hyperoxidized by pervanadate (PV). Both untreated and PV-treated
samples are analyzed by SDS-PAGE and "hyperoxidized" PTPs are detected by
immunoblotting. The proportion of reversibly oxidized PTP-SOH fraction is
determined by the difference between the signals in untreated and the PV-treated
samples.The above immunoassays provide general approaches to detect and quantify
global levels of irreversible protein oxidation and of irreversibly/reversibly
oxidized PTPs in any (patho)physiological context. Characterization of the global
redox status is essential to better understand the redox-sensitive mechanisms
underlying chronic diseases associated with oxidative stress. This is
particularly important in systems influenced by the renin angiotensin system,
because Ang II is a potent inducer of oxidative stress and redox signaling.
PMID- 28500594
TI - Methods for Studying the Role of RAAS in the Modulation of Vascular Repair
Relevant Functions of Stem/Progenitor Cells.
AB - In recent years, previously unknown functions have been conferred to the RAAS and
have been explored in mechanistic studies and disease models. Implication of bone
marrow stem/progenitor cells in the cardiovascular protective or detrimental
effects of RAAS is a prominent advancement because of the translational
significance. Selected members of RAAS are now known to modulate migration,
proliferation, and mobilization of bone marrow cells in response to ischemic
insult, which are sensitive indicators of vascular repair-relevant functions. In
this Chapter, protocols for most frequently used, in vitro, ex vivo, and in vivo
assays to explore the potential of RAAS members to stimulate vascular repair
relevant functions of bone marrow stem/progenitor cells of human and murine
origin.
PMID- 28500595
TI - Use of a Fluorescent Substrate to Measure ACE2 Activity in the Mouse Abdominal
Aorta.
AB - The use of fluorogenic substrates to measure enzymatic activity is widely used to
understand function within different experimental models. ACE2 is important in
understanding the balance between AngII and Ang-(1-7) and how this balance could
then in turn influence hypertension or other disease outcomes. Here, we describe
a method to measure ACE2 activity in abdominal aorta of hyperlipidemic mice under
both saline and AngII infusion.
PMID- 28500596
TI - Measuring Blood Pressure Using a Noninvasive Tail Cuff Method in Mice.
AB - The renin angiotensin system (RAS) is well known for its role in regulating blood
pressure (BP). An activated RAS contributes to elevated blood pressure and is
evident in both human and animal models of hypertension. Drugs that target the
classic vasoconstrictive arm of the RAS (angiotensin II/AT1 receptor signaling)
are potent anti-hypertensive agents in clinical setting. However, the newly
discovered angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1-7)/Mas receptor
axis added new vitality to the hypertension field. Advances in genetic
manipulation and the relative low cost made the mouse model as one of the most
popular animal models to study hypertension. Since a reliable and accurate method
for BP assessment is the key for such experiments, here we provide a protocol for
BP measurement in mice using a noninvasive BP system. The CODA noninvasive BP
system (a tail-cuff Method, Kent Scientific Corporation) enables blood pressure
(BP) measurements in mice. This method uses a specialized volume pressure
recording (VPR) sensor, and measures blood volume changes that are placed over
the animal's tail. Mice do need to be restrained in specific holders and
artificially heated to maintain normal BP.
PMID- 28500597
TI - Blood Pressure Monitoring Using Radio Telemetry Method in Mice.
AB - The TA11PA-C10 implantable transmitter (Data Sciences International, DSI) is
designed to measure blood pressure (BP) and activity in freely moving laboratory
mice. The fluid filled catheter is placed in the free flowing blood of the
systemic artery (inserted into the left carotid artery and extended into the
aorta), and the transmitter body is placed in a benign location for long-term
biocompatibility. The transmitter can be used to monitor BP in mice (as small as
17 g) under normal physiological and unrestricted conditions 24 h a day while
remaining free from stress associated with human interaction. Thus, telemetry is
considered the gold standard for BP monitoring in small animals such as mice.
However, this methodology does require a good understanding of the system as well
as appropriate training to perform the delicate transmitter implantation surgery.
PMID- 28500598
TI - Characterization and Functional Phenotyping of Renal Immune Cells via Flow
Cytometry.
AB - A variety of immune cell subsets contribute to the pathogenesis of hypertension
and associated kidney damage following inappropriate activation of the renin
angiotensin system (RAS). These immune cell subsets often express common surface
markers, which complicates their separation and characterization in vivo.
Accordingly, flow cytometry has become an invaluable tool for parsing immune cell
populations because this technique permits the simultaneous detection of up to 18
markers on a single cell. Below we describe a process by which one can determine
the immune cell subsets in the kidney via flow cytometry.
PMID- 28500599
TI - Assessment of the Renin-Angiotensin System in Cellular Organelle: New Arenas for
Study in the Mitochondria.
AB - The renin-angiotensin system (RAS) is an important hormonal system composed of
various protein and peptide components that contribute to blood pressure
regulation. Although originally characterized as a circulating system, there is
increasing evidence for the intracellular expression of RAS elements on the
nucleus and mitochondria that may function in concert with or independent of the
circulating system. The present chapter describes several experimental approaches
to quantify the expression of RAS components in isolated mitochondria from the
kidney. These approaches are intended to provide a framework to understand the
mitochondrial RAS within a cell-free environment.
PMID- 28500600
TI - Comprehensive Assessments of Energy Balance in Mice.
AB - Increasing evidence supports a major role for the renin-angiotensin system (RAS)
in energy balance physiology. The RAS exists as a circulating system but also as
a local paracrine/autocrine signaling mechanism in target tissues including the
gastrointestinal tract, the brain, the kidney, and distinct adipose beds. Through
activation of various receptors in these target tissues, the RAS contributes to
the control of food intake behavior, digestive efficiency, spontaneous physical
activity, and aerobic and anaerobic resting metabolism. Although the assortment
of methodologies available to assess the various aspects of energy balance can be
daunting for an investigator new to this area, a relatively straightforward array
of entry-level and advanced methodologies can be employed to comprehensively and
quantitatively dissect the effects of experimental manipulations on energy
homeostasis. Such methodologies and a simple initial workflow for the use of
these methods are described in this chapter, including the use of metabolic
caging systems, bomb calorimetry, body composition analyzers, respirometry
systems, and direct calorimetry systems. Finally, a brief discussion of the
statistical analyses of metabolic data is included.
PMID- 28500601
TI - In Vitro Assays to Determine Smooth Muscle Cell Hypertrophy, Protein Content, and
Fibrosis.
AB - This chapter provides information on how to culture primary rat vascular smooth
muscle cells and how to induce cellular changes similar to those associated with
angiotensin II activation in vivo. We describe how to assess the cellular changes
by determining cell size with an automated coulter cell counter to measure cell
volume. In addition, we describe a method to assess total protein content.
Finally, we describe a standard technique to quantify angiotensin II-induced pro
fibrotic response using the Chondrex Sirius Red Total Collagen Detection Kit.
PMID- 28500602
TI - A New Mouse Model for Introduction of Aortic Aneurysm by Implantation of
Deoxycorticosterone Acetate Pellets or Aldosterone Infusion in the Presence of
High Salt.
AB - Dysfunction of the renin-angiotensin-aldosterone system (RAAS) has been
implicated in the etiologies of many cardiovascular diseases, including aortic
aneurysm. In particular, the infusion of angiotensin II (Ang II) in the
apolipoprotein E-deficient mice (apoE-/-) and low density lipoprotein receptor
knockout mice (LDLR-/-) to induce aortic aneurysm has been extensively used in
the field. In contrast, whether aldosterone (Aldo), an essential component of
RAAS and a downstream effector of Ang II, is involved in aortic aneurysm is
largely unknown. Here, we describe a new animal model for induction of aortic
aneurysm in mice in which administration of deoxycorticosterone acetate (DOCA)
and high salt or aldosterone and high salt, but not DOCA or high salt alone, to
C57BL/6 male mice can potently induce aortic aneurysm formation and rupture in an
age-dependent manner. This new aortic aneurysm mouse model is different from Ang
II infusion mouse model and exhibits several unique features that mimic human
aortic aneurysm.
PMID- 28500603
TI - Fluorescence-Based Binding Assay for Screening Ligands of Angiotensin Receptors.
AB - Binding assay is a common technique used to characterize ability of a ligand to
interact with a specific biological target. A number of parameters, such as
binding affinity, receptor density, and association/dissociation rate constants,
can be measured by means of this technique. In most cases, implementation of the
binding assay requires specific infrastructure for labeling and detecting the
ligand, which impedes realization of this technique in a standard laboratory.
Here we describe a simple fluorescence-based binding assay for angiotensin
peptides and receptors, which does not require complex equipment and can be used
for initial screening of the novel ligands or mutational studies.
PMID- 28500606
TI - ?
PMID- 28500604
TI - A Primer to Angiotensin Peptide Isolation, Stability, and Analysis by Nano-Liquid
Chromatography with Mass Detection.
AB - The renin-angiotensin system (RAS) is an important element of cardiovascular and
renal physiology and targeting the RAS by renin inhibitors, angiotensin (Ang)
converting enzyme (ACE) inhibitors and Ang II type 1 receptor antagonists is
effective in the treatment of hypertension, heart failure, and atherosclerosis.
Quantification of Ang peptides is critical to establish the status of the RAS,
but it is challenging due to low Ang peptides concentrations (fmol/mL or fmol/g),
abundance of interfering substances, post sampling conversions, and difficulties
with the specificity of the assay.In this chapter, we describe a new nano-LC/MS
based methodology for comprehensive, specific, sensitive, and accurate
quantification of Ang peptides profile in plasma and tissue. We optimized sample
pretreatment method (protein removal (acetonitrile precipitation) followed by
solid-phase extraction (C18 silica bonded phase)), chromatographic conditions
(reversed-phase nanochromatography with preconcentration), and mass detection
(multiple reaction monitoring) of nine peptides: Ang-(1-12), Ang I (1-10), Ang-(1
9), Ang II (1-8), [Ala1]-Ang II, Ang III (2-8), Ang IV (3-8), Ang-(1-7), and
[Ala1]-Ang-(1-7). Assessment of plasma and cardiac concentrations of Ang peptides
in genetically modified atherosclerotic apolipoprotein E/LDL receptor double
knockout (ApoE-/-/LDLR-/-) mice vs. wild types revealed changes in renin
angiotensin system consistent with an overactivation of ACE and impairment of
ACE2. The method could be easily adopted for high-throughput analysis and for use
in clinical applications such as diagnosis of the RAS abnormalities or monitoring
of the RAS inhibition-based therapies.
PMID- 28500605
TI - Analysis of Angiotensin Metabolism in the Kidney Using Mass Spectrometry.
AB - The renin angiotensin system (RAS) is a highly complex enzymatic system
consisting of multiple peptide hormones, enzymes, and receptors. A thorough
characterization of angiotensin peptide metabolism is crucial for understanding
pathological states associated with an imbalanced RAS. Here, we describe two
matrix-assisted laser desorption/ionization (MALDI) mass spectrometric (MS)
approaches for the assessment of in vitro and in situ RAS enzymatic activities in
the kidney using the natural angiotensin peptide substrates. These MS techniques
demonstrate high specificity and are superior over conventional
spectrophotometric or colorimetric assays since multiple proteolytic cleavage
sites can be detected, thus unraveling the complexity of the RAS.
PMID- 28500607
TI - ?
PMID- 28500608
TI - ?
PMID- 28500609
TI - ?
PMID- 28500610
TI - ?
PMID- 28500611
TI - [Restorative proctocolectomy for ulcerative colitis : Long-term functional
results and quality of life].
AB - Restorative proctocolectomy with ileo-pouch-anal anastomosis is the standard
procedure for ulcerative colitis. It provides complete removal of the diseased
colorectum, avoids permanent ileostomy and allows the preservation of continence.
Functional results and quality of life after restorative proctocolectomy are of
great importance. Patients usually have 5-6 bowel movements per day, and
continence is satisfactory in more than 90% of patients. A good pouch function
strongly correlates with high quality of life. Postoperative septic complications
are the main risk factor for bad pouch function and pouch failure; therefore
nowadays most procedures are performed with a covering ileostomy. Quality of life
is usually impaired by active ulcerative colitis, and restorative proctocolectomy
improves the quality of life up to the level of a healthy reference population.
Taken together, restorative proctocolectomy provides excellent results concerning
function and quality of life.
PMID- 28500612
TI - Electric smog: telemetry interference between ICD and LVAD.
AB - Electromagnetic interferences between implantable cardioverter/defibrillators
(ICD) and left ventricular assist devices (LVAD) impacting telemetry have been
described in previous generations of ICD as well as LVAD, but have been
predominantly overcome in current ICD generations. After introduction of a new
fully magnetically levitated centrifugal continuous-flow circulatory pump, we
report a case of tenacious telemetry interference between the HeartMate 3 LVAD
and an ICD after battery exchange to an Iforia 5. Initialization of the initial
telemetry handshake was only possible using several specific maneuvers
simultaneously. In order to exclude device-device interference, we suggest to
place the ICD above the LVAD before implantation and to test for possible
telemetry interferences.
PMID- 28500613
TI - Functional Diets Modulate lncRNA-Coding RNAs and Gene Interactions in the
Intestine of Rainbow Trout Oncorhynchus mykiss.
AB - The advent of functional genomics has sparked the interest in inferring the
function of non-coding regions from the transcriptome in non-model species.
However, numerous biological processes remain understudied from this perspective,
including intestinal immunity in farmed fish. The aim of this study was to infer
long non-coding RNA (lncRNAs) expression profiles in rainbow trout (Oncorhynchus
mykiss) fed for 30 days with functional diets based on pre- and probiotics. For
this, whole transcriptome sequencing was conducted through Illumina technology,
and lncRNAs were mined to evaluate transcriptional activity in conjunction with
known protein sequences. To detect differentially expressed transcripts, 880
novels and 9067 previously described O. mykiss lncRNAs were used. Expression
levels and genome co-localization correlations with coding genes were also
analyzed. Significant differences in gene expression were primarily found in the
probiotic diet, which had a twofold downregulation of lncRNAs compared to other
treatments. Notable differences by diet were also evidenced between the coding
genes of distinct metabolic processes. In contrast, genome co-localization of
lncRNAs with coding genes was similar for all diets. This study contributes novel
knowledge regarding lncRNAs in fish, suggesting key roles in salmons fed with in
feed additives with the capacity to modulate the intestinal homeostasis and host
health.
PMID- 28500615
TI - Marijuana and the Risk of Fatal Car Crashes: What Can We Learn from FARS and NRS
Data?
AB - Lab studies have shown that marijuana can severely impair driving skills.
Epidemiological studies, however, have been inconclusive regarding the
contribution of marijuana use to crash risk. In the United States, case-control
studies based on the merging of comparable crash Fatality Analysis Reporting
System (FARS) and non-crash National Roadside Survey (NRS) data have been applied
to assess the contribution of drugs to crash risk, but these studies have yielded
confusing, even contradictory results. We hypothesize that such a divergence of
results emanates from limitations in the databases used in these studies, in
particular that of the FARS. The goal of this effort is to examine this
hypothesis, and in doing so, illuminate the pros and cons of using these
databases for drugged-driving research efforts. We took advantage of two
relatively recent cannabis crash risk studies that, despite using similar
databases (the FARS and the NRS) and following similar overall approaches,
yielded opposite results (Li, Brady, & Chen, 2013; Romano, Torres-Saavedra, Voas,
& Lacey, 2014). By identifying methodological similarities and differences
between these efforts, we assessed how the limitations of the FARS and NRS
databases contributed to contradictory and biased results. Because of its
limitations, we suggest that the FARS database should neither be used to examine
trends in drug use nor to obtain precise risk estimates. However, under certain
conditions (e.g., based on data from jurisdictions that routinely test for drugs,
with as little variation in testing procedures as possible), the FARS database
could be used to assess the contribution of drugs to fatal crash risk relative to
other sources of risk such as alcohol.
PMID- 28500614
TI - IRF9-Stat2 Fusion Protein as an Innate Immune Inducer to Activate Mx and
Interferon-Stimulated Gene Expression in Zebrafish Larvae.
AB - Virus infection often causes large amounts of mortality during teleost larvae
stage. Strong induction of innate immunity to increase survival rates of teleost
larvae has been less reported. In this study, we present a zebrafish IRF9-Stat2
fusion protein (zIRF9-S2C) as a strong innate immunity inducer and characterized
induction of interferon-stimulated genes (ISGs) in zebrafish larvae. zIRF9-S2C
could mimic IFN-stimulated gene factor 3 (ISGF3) complex to constitutively
activate transcription of Mx promoter through IFN-stimulatory element (ISRE)
sites. Mutation of two ISRE sites on Mx promoter reduced transactivation
activities of Mx promoter induced by zIRF9-S2C. An electrophoretic mobility shift
assay experiment shows that zIRF9-S2C could directly bind to two ISRE sites of Mx
promoter. Induction of transactivation of Mx promoter by zIRF9-S2C shows
significantly higher activity than by zebrafish IFN1 (zIFN1), IFNgamma
(zIFNgamma), and Tetraodon IRF9-S2C (TnIRF9-S2C). zIRF9-S2C raises transcription
of Mxa, Mxb, Mxc, Ifnphi1, Ifnphi2, and Ifnphi3 in zebrafish liver ((ZFL) cell
line) cells and zebrafish larvae. Collectively, we suggest that IRF9-S2C could
activate transcription of ISGs with species-specific recognition and could be an
innate immunity inducer in teleost larvae.
PMID- 28500616
TI - Significance of blood neutrophil-to-lymphocyte ratio for prognostic
stratification of patients with gastroesophageal junction adenocarcinoma in the
era of the 8th edition of the American Joint Committee on Cancer (AJCC8) staging.
AB - The prognosis of patients with gastroesophageal junction (GOJ) adenocarcinoma
depends mainly on the clinical staging, as described by the new AJCC8 (American
Joint Committee on Cancer 8th edition). Evidence suggests that peripheral blood
neutrophil-to-lymphocyte ratio (NLR) may be of prognostic significance in
patients with upper gastrointestinal cancers. We examined the prognostic
significance of NLR in the era of the new AJCC8 staging system. In this single
centre cohort study, retrospective data on patients with operable GOJ
adenocarcinoma treated with perioperative chemotherapy were analysed. The
prognostic significance of baseline NLR in combination with AJCC8 clinical
staging and other patient characteristics was examined for both time-to
progression (TTP) and overall survival (OS). Of 316 patients, 245 (77.5%)
underwent radical surgery. Fifty-one patients (16.2%) developed unresectable
disease due to early disease progression. NLR was the only baseline factor
independently associated with the development of early disease progression. AJCC8
clinical staging was significantly associated with TTP and OS. In addition, NLR
>= 3 was predictive of poorer TTP (p = 0.001) and OS (p = 0.002), confirmed in
multivariate Cox-regression analysis. NLR >= 3 was prognostic, especially in
patients with clinical stage III for TTP (p = 0.006) and OS (p = 0.025) and in
patients with clinical stage IVA for OS (p = 0.017). NLR significantly improved
the prognostic classification of patients by different AJCC8 clinical stages,
with a c-index improved from 0.554 to 0.592 (p < 0.001). NLR was confirmed to be
an independent prognostic factor in this cohort and could be used in combination
with AJCC8 clinical staging to improve the baseline prognostic stratification of
patients with newly diagnosed resectable GOJ adenocarcinoma.
PMID- 28500617
TI - Post-chemotherapy PD-L1 expression correlates with clinical outcomes in Japanese
bladder cancer patients treated with total cystectomy.
AB - Programmed cell death ligand-1 (PD-L1) is a key target molecule of immunotherapy
that is frequently overexpressed in bladder cancer. In the present study, we
examined whether PD-L1 expression is associated with clinical outcomes in bladder
cancer patients. We enrolled 102 bladder cancer patients treated with cystectomy
at the Aomori Prefectural Hospital between April 2004 and May 2014. We conducted
an immunohistochemical examination of PD-L1 expression using the SP142 assay. PD
L1 expression was scored at three diagnostic levels (0/1/2). Of the 102 patients,
82 were men (81.0%) and 20 were women (19.0%) (mean age 60 years, range 43-84
years). Sixty-six patients (64.8%) had previously undergone neoadjuvant
chemotherapy [neoadjuvant (+) group]. During the mean observation period of 54.5
months, 42 patients had recurring disease (41.1%) and 34 died (33.3%). The 5-year
cause-specific survival (CSS) rate was 66.6%; the 5-year disease-free survival
(DFS) rate was 59.7%. In the neoadjuvant (+) group, the 5-year DFS rate was 65.0%
for PD-L1 (-) patients and 31.7% for PD-L1 (+) patients (log-rank p = 0.006). In
the neoadjuvant (+) groups, the 5-year CSS rate was 69.6% for PD-L1 (-) patients
and 48.1% for PD-L1 (+) patients. Differences in CSS and DFS rates between PD-L1
(-) and PD-L1 (+) patients in both treatment groups were statistically
significant (log-rank p = 0.006 and 0.039, respectively.) Despite the small study
size, our data suggest that post-chemotherapy PD-L1 expression is associated with
poor prognosis in patients receiving neoadjuvant chemotherapy who had previously
undergone cystectomy.
PMID- 28500619
TI - Prevalence of cribra orbitalia in Pacopampa during the formative period in Peru.
AB - Cribra orbitalia is characterized by an aggregation of small apertures in the
orbital roof in response to marrow hypertrophy. This pathological change is
indicative of biological stress during youth. We examined the prevalence of this
lesion in Pacopampa, a ceremonial center of the formative period, located in the
northern highlands of Peru. Using this evaluation of cribra orbitalia, we
reconstructed aspects of the population's health and nutritional status during
the formation of Andean civilization. We examined 41 orbits of 27 adult
individuals (13 males, 14 females) and recorded the macroscopic presence or
absence of cribra orbitalia. The presence or absence of cribra orbitalia was the
same bilaterally for all 14 individuals having both orbits preserved. The
pathology was present in two of the 13 males (15.4%), one of the 14 (7.1%)
females, and three of 27 individuals (11.1%) for both sexes combined. There was
no difference in the frequency between sexes. The prevalence of cribra orbitalia
was found to be lower in Pacopampa than in the comparative data of coastal
populations. It is reasonable to assume that the increase in social complexity in
Pacopampa was probably unrelated to the decline in overall health of the people.
PMID- 28500618
TI - Prognostic value of ABO blood types in young patients with breast cancer; a
nationwide study in Korean Breast Cancer Society.
AB - The purpose of this study was to investigate the relationship between ABO blood
types and breast cancer survival in young Korean patients. This was a
retrospective study of 115,474 patients who were surgically treated for primary
breast cancer between 1987 and 2011 in Korea. All data were collected by the
Korean Breast Cancer Society (KBCS) online breast cancer registry. Each hospital
serologically examined the ABO blood types of patients before surgery. There was
no significant difference in overall survival (OS) or breast cancer-specific
survival (BCSS) among ABO blood types. Type of surgery; T stage; N stage;
histologic grade; status of estrogen receptor, progesterone receptor, and HER2;
and chemotherapy were significant prognostic factors of OS and BCSS in univariate
analysis and multivariate analyses. Compared to women with blood type O, there
was a difference in OS and BCSS for blood type A, blood type B, or blood type AB.
Compared to blood group non-O, patients with blood group O were more likely to
have favorable prognosis when younger than 40 years. Further follow-up studies
are necessary to clarify the role of the impact of ABO blood types on prognosis
of breast cancer.
PMID- 28500620
TI - Relationship between disordered eating and self-identified sexual minority youth
in a sample of public high school adolescents.
AB - PURPOSE: To investigate the relationship between selected disordered eating
behaviors and self-reported sexual minority status (gay/lesbian, bisexual, and
unsure) among a representative sample of high school adolescents. METHODS: The
2013 Centers for Disease Control and Prevention (CDC)-sponsored Connecticut Youth
Risk Behavior Survey was utilized (N = 2242). Unadjusted and adjusted logistic
regression analyses, separated by gender, examined sexual minority adolescents
(gay/lesbian, bisexual, and unsure) and selected eating behaviors. Analyses
adjusted for race, age, cigarette use, binge drinking, organized school activity
participation, body mass index (BMI), and depression. RESULTS: Gay males were
significantly more likely to report exercising or eating less to lose weight in
the unadjusted models (p < 0.05) and fasting, vomiting, and taking diet pills in
both adjusted (p < 0.05) and unadjusted models (p < 0.01) when compared to the
referent heterosexual males. Bisexual females were significantly more likely to
report fasting, vomiting, and taking diet pills in the unadjusted model (p <
0.05) when compared to the referent heterosexual females and significantly less
likely to report exercising or eating less to lose weight in the adjusted models
(p < 0.05). CONCLUSIONS: Although additional studies are needed owing to small
sample sizes, preliminary findings support previous research suggesting that high
school-aged sexual minority youth subgroups are a priority target population for
increased efforts to prevent disordered eating.
PMID- 28500621
TI - Symptoms predicting psychosocial impairment in bulimia nervosa.
AB - PURPOSE: The current study aimed to determine which particular eating disorder
(ED) symptoms and related features, such as BMI and psychological distress,
uniquely predict impairment in bulimia nervosa (BN). METHODS: Two hundred and
twenty-two adults with BN completed questionnaires assessing ED symptoms, general
psychological distress, and psychosocial impairment. Regression analyses were
used to determine predictors which account for variance in impairment. RESULTS:
Four variables emerged as significant predictors of psychosocial impairment:
concerns with eating; concerns with weight and shape; dietary restraint; and
general psychological distress. CONCLUSIONS: Findings support previous work
highlighting the importance of weight and shape concerns in determining ED
related impairment. Other ED symptoms, notably dietary restraint and concerns
with eating, were also significant predictors as was psychological distress.
Results suggest that cognitive aspects of EDs, in addition to psychological
distress, may be more important determinants of impairment than behavioural
symptoms, such as binge eating or purging.
PMID- 28500622
TI - Implementation of a rapid assay of ADAMTS13 activity was associated with improved
30-day survival rate in patients with acquired primary thrombotic
thrombocytopenic purpura who received platelet transfusions.
AB - BACKGROUND: Platelet (PLT) transfusions are probably harmful in patients with
acquired idiopathic thrombotic thrombocytopenic purpura (aTTP). Introduction of a
rapid assay for ADAMTS13 activity should reduce the time to definite diagnosis of
aTTP, reduce the amount of inappropriately transfused PLT concentrates, and
improve mortality and morbidity. STUDY DESIGN AND METHODS: We selected 265 aTTP
patients with severe ADAMTS13 deficiency. Of these, 91 patients were diagnosed by
March 2005 (Period 1), when ADAMTS13 activity was measured by von Willebrand
factor multimer assay, which took 4 to 7 days until the result was reported. An
additional 174 patients were diagnosed after April 2005 (Period 2), when the
activity was measured by a chromogenic enzyme-linked immunosorbent assay, which
took 1 to 2 days. RESULTS: We found no significant differences in 30-day survival
rate between the two periods. Overall, 48 patients received PLT transfusions.
Mortality was slightly greater between patients with (22.9%) versus without PLT
transfusion (17.7%), but not significant. In Period 1, Cox proportional hazards
regression analysis showed that older age (>=60 years) and PLT transfusion
administration were independent factors associated with higher risks of 30-day
mortality. In contrast, in Period 2, lower Rose-Eldor TTP severity score and use
of plasma exchange and corticosteroid therapy were independent factors associated
with higher survival rates while nonadministration of PLT transfusions was not.
CONCLUSION: Our results indicate that PLT transfusions are harmful for aTTP
patients when the definite diagnosis of severe ADAMTS13 deficiency is delayed. If
it can be done as soon as possible, PLT transfusions for severe bleeding or
surgical interventions might be allowed with subsequent plasmapheresis.
PMID- 28500623
TI - Simultaneous inhibition of NMDA and mGlu1/5 receptors by levo-corydalmine in rat
spinal cord attenuates bone cancer pain.
AB - Bone cancer pain is a challenge for its not completely clarified mechanism and
broad clinical morbidity. Therefore, novel and more effective drugs are urgent
needed for improvement of patients' quality of life. Glutamate receptors have
been associated with the development of the central sensitization of chronic
pain. Inhibition of N-methyl-d-aspartate (NMDA) and metabotropic glutamate (mGlu)
receptors can effectively attenuate bone cancer pain, respectively. Herein, our
results indicated that levo-Corydalmine (l-CDL), a compound from Corydalis
yanhusuo W.T. Wang, which has been used in traditional Chinese medicine for pain
relief could effectively attenuate bone cancer pain induced by tibia bone cavity
tumor cell implantation (TCI) through simultaneously inhibiting the NMDA and
mGlu1/5 receptors in rat spinal cord without notable side effects. Both
intragastric and intrathecal administration of l-CDL significantly alleviated the
mechanical hypersensitivity induced by TCI in rats, and the analgesic effect of l
CDL could be reversed by intrathecal administration of NMDA receptor agonist NMDA
and mGlu1/5 receptor agonist DHPG but not AMPA receptor agonist AMPA. l-CDL could
also selectively suppress NMDA and DHPG induced rapid rise in Ca2+ oscillations
in primary cultures neurons of spinal cord in vitro. The antinociception of l-CDL
were partially mediated by the reduced phosphorylation of PKC gamma and ERK1/2 in
spinal cord of TCI rats in a NMDA and mGlu1/5 dependent manner. In conclusion,
these results suggested that l-CDL attenuates TCI induced bone cancer pain
through simultaneously inhibiting the NMDA and mGlu1/5 receptors and the
downstream PKC gamma, ERK1/2 signaling pathways in the spinal cord.
PMID- 28500624
TI - Temporal trends in thyroid-stimulating hormone (TSH) and thyroid peroxidase
antibody (ATPO) testing across two phases of iodine fortification in Tasmania
(1995-2013).
AB - CONTEXT: Tasmania is an island state of the Australian Commonwealth with a well
documented history of mild iodine deficiency. Between 2001 and 2009, Tasmania
experienced two incremental phases of iodine fortification. OBJECTIVE: To examine
trends in thyroid-stimulating hormone (TSH) and thyroid peroxidase antibody
(ATPO) testing and their relationship to different phases of iodine nutrition in
the Tasmanian population between 1995 and 2013. DESIGN: Retrospective
longitudinal study. SETTING AND PARTICIPANTS: The major primary care and largest
public hospital pathology providers in Tasmania submitted data for all TSH and
ATPO tests performed between 1995 and 2013. Data linkage methodology was used to
determine trends in TSH and ATPO testing. RESULTS: A total of 1.66 million TSH
assessments, involving 389,910 individual patients, were performed in Tasmania
between 1995 and 2013. There was approximately a fourfold increase in the overall
rate of TSH testing during this period with the rate of incident TSH assessment
remaining relatively stable over the study period. The incidence of overt
suppression and elevation of TSH (TSH<=0.1 mIU/L and >=10 mIU/L) declined 62.3%
and 59.7%, respectively, with a trend for increased incidence of borderline TSH
elevation >=4.0 mIU/L. The incidence of thyroid autoimmunity as determined by the
proportion of abnormal ATPO results remained stable, with the absolute number of
positive test results increasing during the study period. CONCLUSION: Iodine
supplementation of this mildly iodine-deficient population was not associated
with an obvious increase in incidence of overt thyroid dysfunction or
autoimmunity. Whilst the volume of TSH testing increased over the study period,
the increase was driven by patients undergoing follow-up TSH assessments.
PMID- 28500625
TI - Adopting automated image analysis tool for fibrin network: Can we obtain clot
properties for practical application?
PMID- 28500626
TI - Using Eulerian video magnification to enhance detection of fasciculations in
people with amyotrophic lateral sclerosis.
AB - INTRODUCTION: This study seeks to determine whether the use of Eulerian video
magnification (EVM) increases the detection of muscle fasciculations in people
with amyotrophic lateral sclerosis (PALS) compared with direct clinical
observation (DCO). METHODS: Thirty-second-long video recordings were taken of 9
body regions of 7 PALS and 7 controls, and fasciculations were counted by DCO
during the same 30-s period. The video recordings were then motion magnified and
reviewed by 2 independent assessors. RESULTS: In PALS, median fasciculation count
per body region was 1 by DCO (range 0-10) and 3 in the EVM recordings (range 0
15; P < 0.0001). EVM revealed more fasciculations than DCO in 61% of recordings.
In controls, median fasciculation count was 0 for both DCO and EVM. DISCUSSION:
Compared with DCO, EVM significantly increased the detection of fasciculations in
body regions of PALS. When it is used to supplement clinical examination, EVM has
the potential to facilitate the diagnosis of ALS. Muscle Nerve 56: 1063-1067,
2017.
PMID- 28500627
TI - Widespread biphasic amyloidosis related to ipilimumab treatment for metastatic
melanoma.
PMID- 28500628
TI - Nonconvulsive electrotherapy in psychiatry: The treatment of the mental disorders
of the Norwegian painter Edvard Munch.
PMID- 28500629
TI - Early Prediction Tool to Identify the Need for Pharmacotherapy in Infants at Risk
of Neonatal Abstinence Syndrome.
AB - OBJECTIVE: To develop a tool to predict the need for pharmacologic treatment of
neonatal abstinence syndrome (NAS) within 36 hours from birth in infants at risk
for opioid withdrawal. STUDY DESIGN: Retrospective study of infants born at
gestation of >=34 weeks with in utero exposure to opioids during two time periods
from January 2013 through October 2016. Period 1 was used to develop a predictive
tool for validation during period 2. Birth weight, gestational age, four
categories of opioid exposure, and individual scores for 21 withdrawal symptoms
from the Modified Finnegan Score at 36 hours of life were recorded. During period
1, a best subsets multiple regression analysis was performed on factors that were
associated with pharmacotherapy on univariate analysis. Two tools were designed:
one based on three highly predictive symptoms associated with need for
pharmacotherapy for NAS and the other incorporating opioid exposure. Sensitivity,
specificity, and positive and negative predictive values for the tools were
calculated during period 2. RESULTS: The study included 264 infants (period 1,
n=143; period 2, n=121). Polysubstance exposure and three withdrawal symptoms
present at 36 hours of life that were significantly associated with
pharmacotherapy for NAS comprised the tools. The "symptoms only tool" was able to
predict that infants with a score <1 would not receive pharmacotherapy, and
infants with scores of >=4 would receive pharmacotherapy with positive predictive
values of 90% and 100%, respectively. When opioid exposure was included, the
"symptoms + exposure tool" was able to predict that infants with a score of <=1
would not receive pharmacotherapy and infants with scores of >=5 would receive
pharmacotherapy with positive predictive values of 94% and 86%, respectively.
CONCLUSION: An NAS prediction tool combining three clinical signs with and
without category of opioid exposure had high positive predictive values for
requiring and for not requiring pharmacotherapy. This tool may expedite
pharmacotherapy decisions and optimize management for infants at risk for NAS.
PMID- 28500631
TI - Exploring the value of mental health nurses working in primary care in England: A
qualitative study.
AB - : WHAT IS KNOWN ON THE SUBJECT?: Primary care and, in particular, general
practice (GP) are often first point of access to health care. International
evidence suggests that healthcare systems oriented towards primary care may
produce better outcomes, at lower costs and with higher user satisfaction.
Despite this, there are noted deficiencies and variations in the quality of care
in primary care for patients with mental health problems. WHAT THIS PAPER ADDS TO
EXISTING KNOWLEDGE?: Emerging models of providing mental health services in
primary care are poorly understood. This paper evaluates a mental health nurse
led Primary Care Liaison Service (PCLS), developed in 2011 in inner London. The
findings suggest that this type of service can improve the quality of care for
people presenting with mental health problems within primary care, specifically
due to improved integration, clinical effectiveness, patient-centred care, access
and efficiency. The study also highlighted challenges such as staff retention
within this new role and setting appropriate referral criteria. WHAT ARE THE
IMPLICATIONS FOR PRACTICE?: This is a relatively new service, and the cost
effectiveness is not yet fully understood; however, commissioners may want to
consider the potential benefits of a similar service in their area. The extent to
which the findings are transferable will depend on service configuration and
local demographics which can vary. Further research within this area could give
more detail on the impact of such teams on health outcomes, recovery rates,
secondary care referrals and accident and emergency attendances, and its cost
effectiveness. ABSTRACT: Aims/Question General practice is typically the first
point of access to healthcare. This study explores what value a Primary Care
Liaison Nurse (PCLN) service, established in 2011, can bring to people with
mental health problems in primary care. Method Semi-structured interviews were
used to elicit participants' experiences and perspectives on the value of a PCLN
service. Participants included ten interviews with seven general practitioners
and three senior practitioners working in primary care mental health services.
Thematic analysis, based on a 6-phase approach, was used to describe and explore
the data collected. Results Five main themes were derived from the thematic
analysis of the interviews relating to: integration; clinical effectiveness;
patient centred care; access; and efficiency. Discussion The study suggests that
the PCLN service can improve the quality of care and is generally highly valued
by its stakeholders. The study identifies particularly valued elements of the
service, including having a duty worker, as well as aspects which could be
improved, such as patient criteria. Implications for practice This is a
relatively new service and the cost-effectiveness is not yet fully understood;
however, commissioners may want to consider the potential benefits of a similar
service in their area.
PMID- 28500630
TI - E2F is involved in radioresistance of carbon ion induced apoptosis via
Bax/caspase 3 signal pathway in human hepatoma cell.
AB - Deletion of p53, most common genetic alteration, is observed in human tumors and
reported to lead to improve in cell radioresistance. Heavy-ion irradiation (IR)
could induce p53-/- cancer cells apoptosis. However, little is known regarding
the molecular mechanism in this type of cell apoptosis. The present studies have
focused on mechanisms state of signaling pathways as an activator of the cell
fate decisions induced by heavy ion IR without p53. Carbon ion IR could induce up
regulation of E2F1 expression in cancer cells. This phenomenon was not observed
in X-ray IR group. Up-regulation of E2F1 could cause a higher reduction in
clonogenic survival, low level of cellular activity, G2 /M phase arrest,
promotion of apoptosis rate, up-regulation of phosphor-Rb, Bax, and cleaved
caspase 3 proteins expressions without p53. Changes of E2F1 expressions could
partly alter radioresistance in cancer cells. The results were suggested that
heavy ion IR could induce p53-/- cancer cells apoptosis via E2F1 signal pathway.
Our study provides a scientific rationale for the clinical use of heavy ion as
radiotherapy in patients with p53-deficient tumors, which are often resistant to
radiotherapy.
PMID- 28500632
TI - Altered expression of four miRNA (miR-1238-3p, miR-202-3p, miR-630 and miR-766
3p) and their potential targets in peripheral blood from vitiligo patients.
AB - Vitiligo is an acquired skin disease with pigmentary disorder. Autoimmune
destruction of melanocytes is thought to be major factor in the etiology of
vitiligo. miRNA-based regulators of gene expression have been reported to play
crucial roles in autoimmune disease. Therefore, we attempt to profile the miRNA
expressions and predict their potential targets, assessing the biological
functions of differentially expressed miRNA. Total RNA was extracted from
peripheral blood of vitiligo (experimental group, n = 5) and non-vitiligo
(control group, n = 5) age-matched patients. Samples were hybridized to a miRNA
array. Box, scatter and principal component analysis plots were performed,
followed by unsupervised hierarchical clustering analysis to classify the
samples. Quantitative reverse transcription polymerase chain reaction (RT-PCR)
was conducted for validation of microarray data. Three different databases,
TargetScan, PITA and microRNA.org, were used to predict the potential target
genes. Gene ontology (GO) annotation and pathway analysis were performed to
assess the potential functions of predicted genes of identified miRNA. A total of
100 (29 upregulated and 71 downregulated) miRNA were filtered by volcano plot
analysis. Four miRNA were validated by quantitative RT-PCR as significantly
downregulated in the vitiligo group. The functions of predicted target genes
associated with differentially expressed miRNA were assessed by GO analysis,
showing that the GO term with most significantly enriched target genes was axon
guidance, and that the axon guidance pathway was most significantly correlated
with these miRNA. In conclusion, we identified four downregulated miRNA in
vitiligo and assessed the potential functions of target genes related to these
differentially expressed miRNA.
PMID- 28500633
TI - The novel role of pyrvinium in cancer therapy.
AB - Pyrvinium pamoate (PP) is a quinoline-derived cyanine dye which was officially
approved by FDA for its anthelmintic properties and therapeutic function against
animal-like protists such as Cryptosporidium parvum and Plasmodium falciparum in
the 1950s. In the last 10 years, several studies have shown the novel activity of
pyrvinium in tumor therapy. Some investigations have indicated that pyrvinium
could delay or inhibit tumor cell proliferation in cancer models including colon,
breast, lung and prostate cancer, and some hematological malignancies. In this
review, we discuss multiple critical signaling pathways and mechanisms underlying
the anticancer effects of PP. In details, pyrvinium acts through the following
main mechanisms: (i) energy and autophagy depletion; and (ii) inhibition of Akt
and Wnt-beta-catenin-dependent pathways. Interestingly, pyrvinium has also shown
potent anti-cancer stem cell activity. The overwhelming insights into the
mechanism of anticancer properties of PP can help establishing novel and future
anti-tumor treatment strategies.
PMID- 28500634
TI - Inhibition of mast cell infiltration in an LL-37-induced rosacea mouse model
using topical brimonidine tartrate 0.33% gel.
AB - Brimonidine is a highly selective alpha2-adrenergic receptor agonist approved by
the FDA for the treatment of rosacea. Rosacea is a major clinical disease with
vasodilatation and rash on the centre of the face, and that brimonidine as a
vasoconstrictor can act as a remedy for rosacea. However, there is no study of
how brimonidine has an effect on rosacea-related immune cells or mechanisms in
the skin to improve rosacea. In this study, we observed that clinical features of
rosacea induced by LL-37 in Balb/c mice were improved after the application of
brimonidine gel, and we also showed a marked decrease in the number of
inflammatory cells, especially mast cells (MCs) histologically. Furthermore, we
confirmed that mRNA levels of MC enzymes increased by LL-37 were reduced by
brimonidine gel. To our knowledge, we first found that brimonidine has a
mechanism of treating rosacea by reducing the number and mRNA levels of MC
specific enzymes, an important immune cell in the pathogenesis of rosacea.
PMID- 28500636
TI - Immune correlates of hepatitis B surface antigen spontaneous seroconversion in
hepatitis B e antigen negative chronic hepatitis B patients.
AB - BACKGROUND: Hepatitis B surface antigen (HBsAg) seroconversion in HBeAg -ve
chronic hepatitis B (CHB) infection is rare, possibly due to poor antigen
processing and impaired humoral response. We investigated the role of dendritic
cells (DCs), T follicular helper (TFH) cells and plasma B cells in
seroconversion. METHODS: HBeAg -ve (n=135) CHB patients with raised ALT at
baseline were followed up. Patients undergoing HBsAg seroconversion (Gr. I, n=11)
were compared with non-converters with low (Gr. II, n=17, HBV DNA<2000 IU/mL) or
high HBV DNA (Gr. III, HBV DNA >2000 IU/mL, n=17). We measured cell phenotypes
(TFH, B and DCs), HBV specific T-cell functionality [using pooled overlapping
surface and core peptides], IL21 levels and gene expression analysis by qRT-PCR.
RESULTS: Patients in Gr. I compared to Gr. II and III, had higher IL-21 levels
(865 vs 276 vs 111 pg/mL, P=<.0001), TFH (CD4+ CXCR5+ ) cells (12.3 vs 4.67 vs
2.77, P=<.001), inducible T-cell co-stimulator (ICOS) expression on TFH cells
(20.0 vs 13.0 vs 13.68, P=.01), HBsAg specific IL-17 (9.40 vs 2.33 vs 2.61,
P=<.001) and TNF-alpha secreting TFH17 cells (82 vs 1.43 vs 2.33, P=<.001),
plasma B (CD19+ CD38+ ) cells (15.0 vs 5.08 vs 5.57, P=<.001), myeloid (17.80 vs
5.39 vs 2.70, P=<.001) and plasmocytoid DCs (2.6 vs 0.43 vs 0.21, P=<.001).
Plasma B-cell frequency (R2 =.64, P=.01) and IL-21 levels (R2 =.52, P=.003)
correlated with anti-HBs titres in patients with HBsAg seroconversion.
CONCLUSIONS: Dendritic cell and TFH cell mediated responses regulate humoral
responses against HBV and play a major role in HBsAg seroconversion in CHB
patients.
PMID- 28500637
TI - Randomized controlled trials in status epilepticus: Size matters.
PMID- 28500635
TI - Principles of pharmacological research of nutraceuticals.
AB - LINKED ARTICLES: This article is part of a themed section on Principles of
Pharmacological Research of Nutraceuticals. To view the other articles in this
section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc.
PMID- 28500638
TI - Adult intestinal colonization botulism mimicking brain death.
PMID- 28500640
TI - Dysregulation of the MEK/ERK/MNK1 signalling cascade by middle T antigen of the
trichoydsplasia spinulosa polyomavirus.
AB - BACKGROUND: Trichodysplasia spinulosa (TS) is a disfiguring folliculocentric
cutaneous disease caused by infection with the trichodysplasia spinulosa
polyomavirus (TSPyV). The TSPyV genome contains splice variants encoding the
middle tumour (mT) antigen, although the potential role for TSPyV mT antigen in
disease development remains unknown. OBJECTIVE: The current study was designed to
investigate the mechanistic properties of TSPyV mT antigen, which may further our
understanding of TS pathogenesis and provide insight into potential therapies.
METHODS: A lentiviral packaging system was used to create an inducible cell line
expressing TSPyV mT antigen. Proteins were extracted, separated by SDS-PAGE and
subjected to Western blot analysis. Co-immunoprecipitation experiments and
mutational analyses were also performed to evaluate protein-protein interactions
of mT antigen. RESULTS: We describe a novel mechanism of action for mT antigen
that involves hyperactivation of MEK, ERK and MNK1. Our findings suggest that
dysregulation of these key signalling molecules depends upon TSPyV mT antigen
interaction with protein phosphatase 2A (PP2A) via intact Zn binding motifs.
CONCLUSION: Given that PP2A interaction and MEK/ERK/MNK1 phosphorylation are
associated with high levels of cell proliferation and inflammation, our findings
provide new evidence that TSPyV mT antigen may contribute to the pro
proliferative conditions that lead to TS development.
PMID- 28500639
TI - Comparison of transfusion thresholds during neonatal extracorporeal membrane
oxygenation.
AB - BACKGROUND: The objective of this study was to assess complications and patient
outcomes associated with a lower reflexive red blood cell (RBC) transfusion
threshold for neonates undergoing extracorporeal membrane oxygenation (ECMO) for
hypoxic respiratory failure. STUDY DESIGN AND METHODS: A retrospective cohort
study was conducted at a single tertiary neonatal intensive care unit of neonates
undergoing ECMO support for refractory hypoxic respiratory failure for more than
24 hours between December 2009 and December 2014. Seventy-two neonates received
ECMO support for hypoxic respiratory failure for longer than 24 hours during the
study period. Patient cohorts were determined based on transfusion threshold of
hematocrit (Hct) level of less than 40% (December 2009-October 2012) and Hct
level of less than 35% (November 2012-December 2014). RESULTS: Patients who had a
lower threshold for transfusion (Hct < 35) had a lower mean Hct (38.3% vs. 41.4%,
p < 0.0001) and received less total RBC transfusion volume (10.4 mL/kg/day vs.
13.3 mL/kg/day, p = 0.002) while undergoing ECMO support. Survival off ECMO,
survival to discharge, and complication rates were similar between the cohorts.
CONCLUSIONS: A lower Hct threshold of 35% is associated with a reduction in RBC
transfusion volume and does not appear to alter complication rates or patient
outcomes for neonates receiving ECMO support for respiratory failure.
PMID- 28500642
TI - Toward meaningful outcomes in teaching conversation and greeting skills with
individuals with autism spectrum disorder.
AB - We identified greeting and conversation deficits based on a parent interview and
semistructured direct assessment for one child and two adolescents with autism
spectrum disorder. We taught the greeting and conversation skills using
behavioral skills training and within-session corrective feedback. A multiple
baseline across conversation and greeting skills demonstrated experimental
control over the effects of the teaching on acquisition and generalization to
novel adults. We also conducted embedded reversals to assess maintenance of the
acquired skills. Teaching produced robust acquisition, generalization,
maintenance, and treatment extension for 15 of the 16 targeted skills across
participants. Participant and parent reports indicated high levels of social
validity for the intervention and outcomes. The results support individualized
assessment and intervention for improving greeting and conversation skills during
unscripted interactions, which are requisite for more extended and complex social
interactions.
PMID- 28500641
TI - T and B cell clonal expansion in Ras-associated lymphoproliferative disease
(RALD) as revealed by next-generation sequencing.
AB - Ras-associated lymphoproliferative disease (RALD) is an autoimmune
lymphoproliferative syndrome (ALPS)-like disease caused by mutations in Kirsten
rat sarcoma viral oncogene homologue (KRAS) or neuroblastoma RAS viral (V-Ras)
oncogene homologue (NRAS). The immunological phenotype and pathogenesis of RALD
have yet to be studied extensively. Here we report a thorough immunological
investigation of a RALD patient with a somatic KRAS mutation. Patient lymphocytes
were analysed for phenotype, immunoglobulin levels and T cell proliferation
capacity. T and B cell receptor excision circles (TREC and KREC, respectively),
markers of naive T and B cell production, were measured serially for 3 years. T
and B cell receptor repertoires were studied using both traditional assays as
well as next-generation sequencing (NGS). TREC and KREC declined dramatically
with time, as did T cell receptor diversity. NGS analysis demonstrated T and B
clonal expansions and marked restriction of T and B cell receptor repertoires
compared to healthy controls. Our results demonstrate, at least for our reported
RALD patient, how peripheral T and B clonal expansions reciprocally limit
lymphocyte production and restrict the lymphocyte receptor repertoire in this
disease. Decreased naive lymphocyte production correlated with a clinical
deterioration in our patient's immune status, suggesting that TREC and KREC may
be used as an aid in monitoring disease progression. Both the methodologies used
here and the conclusions regarding immune homeostasis may be applicable to the
research of ALPS and other immune dysregulation syndromes.
PMID- 28500643
TI - Markers of the innate immune system in the cerebrospinal fluid in patients with
severe depression.
PMID- 28500644
TI - Stimulation of autophagy prevents intestinal mucosal inflammation and ameliorates
murine colitis.
AB - BACKGROUND AND PURPOSE: Defective autophagy contributes to the pathogenesis of
inflammatory disorders such as inflammatory bowel disease and there are
interactions between autophagy and inflammation. Here we have analysed the
effects of autophagy stimulators on murine colitis. EXPERIMENTAL APPROACH: Mice
were treated with intrarectal administration of 2,4,6-trinitrobenzenesulfonic
acid (TNBS) (3.5 mg.20 g-1 ) and body weight was measured daily. Histological
damage was scored 2 or 4 days after treatment. Some mice received trehalose (3%
in drinking water 3 weeks before TNBS administration) or a daily administration
of rapamycin (1.25 mg.kg-1 , i.p.), betanin (1 g.kg-1 , i.p.) or betanin + 3
methyladenine (3MA) (10 mg.kg-1 , i.p.). Protein levels of p-mTOR, p62, LC3,
BCL10, NFkappaB, IkappaBalpha and p-IkappaBalpha in mucosa were determined by
Western blots and mRNA expression of TNFalpha, IL1beta, IL6, IL10, COX2, CCR7,
CD11c, inducible NOS and CD86 by qRT-PCR. KEY RESULTS: Impaired autophagy
associated with body weight loss and intestinal damage was detected in the mucosa
of TNBS-treated mice. Administration of trehalose, rapamycin or betanin prevented
the impaired autophagic flux induced by TNBS and decreased mucosal protein levels
of BCL10, p-IkappaBalpha and NFkappaB-p65 and the expression of pro-inflammatory
cytokines and M1 macrophage markers. Blockade of autophagosome formation by
treatment with 3MA, prevented the reduction in protein levels of p62, BCL10, p
IkappaBalpha and NFkappaB-p65 induced by betanin in TNBS-treated mice and
weakened the protective effects of betanin on murine colitis. CONCLUSIONS AND
IMPLICATIONS: Pharmacological stimulation of mucosal autophagy reduced intestinal
inflammation and improved murine colitis.
PMID- 28500645
TI - Development and validation of an LC-ESI-MS/MS approach to determine a highly
hydrophobic drug, norcantharidin palmitate, and apply to a preliminary
pharmacokinetic study in rats.
AB - In order to investigate the pharmacokinetics of norcantharidin palmitate (NCTD
PAL) in rats, we developed and validated an LC-ESI-MS/MS method. The NCTD-PAL and
internal standard (triamcinoloneacetonide palmitate, TAP) were separated on a
Phenomenex Kinetex(r)XB C18 column, and the mobile phase was composed of
tetrahydrofuran (THF)-acetonitrile (20/80, v/v) and an aqueous phase containing
0.2% ammonium hydroxide at a flow rate of 0.3 mL/min. The ESI interface operated
in positive mode was used to acquire the mass spectrometric data, and the
transition ions were m/z 635.50 -> 168.95 and 673.65 -> 397.13 for NCTD-PAL and
IS, respectively. The method had a linear range of 10-2000 ng/mL with a
correlation coefficient of >0.99. The accuracy (RE, %) was within +/-10.1%, and
the intra- and inter-day precisions (RSD, %) were 10.9 and 13.8%, respectively.
The extraction recovery of NCTD-PAL at different concentrations ranged from 89.3
to 102.0%. The validated approach was efficaciously applied to a pharmacokinetic
study of NCTD-PAL in rats via intravenous injection. Based on these results
obtained, this method is practical and suitable for a wide range of applications.
PMID- 28500646
TI - High-throughput metabolic profiling based on small amount of hepatic cells.
AB - Common metabolomics platforms require about 106 cells, which has a limited
throughput due to the time-consuming steps of cell culture and preparation. There
is a demand for metabolic profiling methods to improve analytical throughput and
detection sensitivity based on small amount of cells. In this study, we proposed
a high-throughput scheme, integrating 96-well plate cell cultivation, in-situ
cell pretreatment, and sensitive dansylation labeling coupled with LC-MS analysis
of metabolites inside HepG2 cells (of the order of magnitude of 103 cells in each
well). A simple and rapid cell pretreatment was performed showing good extraction
efficiency and good precision (the RSDs smaller than 5%) for polar metabolites.
The recovery in metabolite extraction evaluated with three isotope-labeled amino
acids was from 89.7 to 106.3% at low, medium, and high concentrations. The
suitability of the method was illustrated by exploring influences of different
fatty acids on HepG2 cells.
PMID- 28500647
TI - Serum brain-derived neurotrophic factor and interleukin-6 response to high-volume
mechanically demanding exercise.
AB - INTRODUCTION: The aim of this study was to follow circulating brain-derived
neurotrophic factor (BDNF) and interleukin-6 (IL-6) levels in response to severe
muscle-damaging exercise. METHODS: Young healthy men (N = 10) performed a bout of
mechanically demanding stretch-shortening cycle exercise consisting of 200 drop
jumps. Voluntary and electrically induced knee extension torque, serum BDNF
levels, and IL-6 levels were measured before and for up to 7 days after exercise.
RESULTS: Muscle force decreased by up to 40% and did not recover by 24 hours
after exercise. Serum BDNF was decreased 1 hour and 24 hours after exercise,
whereas IL-6 increased immediately and 1 hour after but recovered to baseline by
24 hours after exercise. IL-6 and 100-Hz stimulation torque were correlated (r =
0.64, P < 0.05) 24 hours after exercise. DISCUSSION: In response to acute, severe
muscle-damaging exercise, serum BDNF levels decrease, whereas IL-6 levels
increase and are associated with peripheral fatigue. Muscle Nerve 57: E46-E51,
2018.
PMID- 28500649
TI - A comparative study using thrombin generation and three different INR methods in
patients on Vitamin K antagonist treatment.
AB - INTRODUCTION: Vitamin K antagonist (VKA) treatment requires routine monitoring
using the international normalized ratio (INR). However, different INR assays may
vary in their results. The aim of this study was to assess the agreement of three
different INR methods, compared with thrombin generation, in patients on VKA
treatment. METHODS: Sixty patients attending the Anticoagulation Clinic at Mater
Dei Hospital (Msida, Malta) for VKA monitoring between August and September 2015
were enrolled. The INR was tested using a point-of-care (POC) device (CoaguChek
XS Plus, Roche Diagnostics) for both capillary and venous blood samples, a photo
optical (Sysmex CS-2100i/CA-1500, Siemens) and a mechanical clot detection system
(Thrombolyzer XRC, Behnk Elektronik). All assays used human recombinant
thromboplastin as reagent. Thrombin generation was performed using the calibrated
automated thrombogram. RESULTS: There was a negative curvilinear correlation
between the endogenous thrombin potential and different INR assays (r<=-.75) and
a strong positive linear correlation between the CoaguChek XS Plus on capillary
samples and the other INR methodologies (r>=.96). CONCLUSION: All different INR
assays showed good correlation with the thrombin generation potential. The POC
INR showed one of the highest correlation coefficients with thrombin generation,
confirming the POC devices as an accurate, valid alternative to laboratory INR in
VKA patients.
PMID- 28500650
TI - Aberrant cognitive phenotypes and altered hippocampal BDNF expression related to
epigenetic modifications in mice lacking the post-synaptic scaffolding protein
SHANK1: Implications for autism spectrum disorder.
AB - Autism spectrum disorder (ASD) is a class of neurodevelopmental disorders
characterized by persistent deficits in social communication/interaction,
together with restricted/repetitive patterns of behavior. ASD is among the most
heritable neuropsychiatric conditions, and while available evidence points to a
complex set of genetic factors, the SHANK gene family has emerged as one of the
most promising candidates. Here, we assessed ASD-related phenotypes with
particular emphasis on social behavior and cognition in Shank1 mouse mutants in
comparison to heterozygous and wildtype littermate controls across development in
both sexes. While social approach behavior was evident in all experimental
conditions and social recognition was only mildly affected by genotype, Shank1-/-
null mutant mice were severely impaired in object recognition memory. This effect
was particularly prominent in juveniles, not due to impairments in object
discrimination, and replicated in independent mouse cohorts. At the
neurobiological level, object recognition deficits were paralleled by increased
brain-derived neurotrophic factor (BDNF) protein expression in the hippocampus of
Shank1-/- mice; yet BDNF levels did not differ under baseline conditions. We
therefore investigated changes in the epigenetic regulation of hippocampal BDNF
expression and detected an enrichment of histone H3 acetylation at the Bdnf
promoter1 in Shank1-/- mice, consistent with increased learning-associated BDNF.
Together, our findings indicate that Shank1 deletions lead to an aberrant
cognitive phenotype characterized by severe impairments in object recognition
memory and increased hippocampal BDNF levels, possibly due to epigenetic
modifications. This result supports the link between ASD and intellectual
disability, and suggests epigenetic regulation as a potential therapeutic target.
PMID- 28500651
TI - Predictors of Response in Emergency Department Patients Receiving Intravenous
Opioids for Severe Pain.
AB - The primary objective of this study was to identify significant environmental and
patient characteristics of emergency department (ED) patients who responded to
intravenous (IV) hydromorphone and IV morphine for severe pain. Secondary
objectives were to investigate the individual effect of the significant
environmental and patient characteristics of responders, and to assess the nature
and strength of the correlation of initial dose and change in pain score from
arrival to pre-administration. A retrospective chart review was performed in
patients who received IV hydromorphone or morphine in the ED for severe pain. Key
evaluated patient characteristics included patient demographics, recent opioid
use, history of drug or alcohol abuse, and pain location, among others. Key
evaluated environmental characteristics included initial opioid administered,
time to first dose, initial pain score, and initial dose of opioid administered,
among others. Environmental and patient characteristics associated with response
to pain management were first identified using bivariate analyses and then
entered into a multiple stepwise logistic regression mode. Patients were excluded
if they were younger than 18 years, did not have a follow-up pain score within 2
hours of drug administration, or if they were discharged from the ED within 1
hour of administration. Patients meeting the inclusion criteria were grouped into
two cohorts based on response and lack of response to treatment. A total of 200
patients were included. A decrease in pain score from arrival until pre
administration pain score and an inactive tobacco history had a positive
association with response (odds ratio [OR] 1.488, 95% confidence interval [CI]
1.088-2.036, p=0.013, and OR 1.835, 95% CI 0.801-4.200, overall p=0.022,
respectively). A higher initial dose and an active tobacco history had a negative
association with response (OR 0.715, 95% CI 0.580-0.881, p=0.002, and OR 0.582,
95% CI 0.296-1.144, overall p=0.022, respectively). Two characteristics were
associated with response to IV opioid pain management in the ED, inactive tobacco
history and an increase in pain score from arrival until pre-administration, and
two characteristics were associated with nonresponse to IV opioid pain management
in the ED, active tobacco history and a higher initial dose. Previous literature
supports both characteristics identified as risk factors but does not support
either characteristic identified as protective factors, prompting the need for
further research.
PMID- 28500652
TI - Freeze-dried plasma enhances clot formation and inhibits fibrinolysis in the
presence of tissue plasminogen activator similar to pooled liquid plasma.
AB - BACKGROUND: Systemic hyperfibrinolysis is an integral part of trauma-induced
coagulopathy associated with uncontrolled bleeding. Recent data suggest that
plasma-first resuscitation attenuates hyperfibrinolysis; however, the
availability, transport, storage, and administration of plasma in austere
environments remain challenging and have limited its use. Freeze-dried plasma
(FDP) is a potential alternative due to ease of storage, longer shelf life, and
efficient reconstitution. FDP potentially enhances clot formation and resists
breakdown better than normal saline (NS) and albumin and similar to liquid
plasma. STUDY DESIGN AND METHODS: Healthy volunteers underwent citrated blood
draw followed by 50% dilution with NS, albumin, pooled plasma (PP), or pooled
freeze-dried plasma (pFDP). Citrated native and tissue plasminogen activator (t
PA)-challenge (75 ng/mL) thrombelastography were done. Proteins in PP, pFDP, and
albumin were analyzed by mass spectroscopy. RESULTS: pFDP and PP had superior
clot-formation rates (angle) and clot strength (maximum amplitude) compared with
NS and albumin in t-PA-challenge thrombelastographies (angle: pFDP, 67.9 degrees;
PP, 67.8 degrees; NS, 40.6 degrees; albumin, 35.8 degrees; maximum amplitude:
pFDP, 62.4 mm; PP, 63.5 mm; NS, 44.8 mm; albumin, 41.1 mm). NS and albumin
dilution increased susceptibility to t-PA-induced hyperfibrinolysis compared with
pFDP and PP (NS, 62.4%; albumin, 62.6%; PP, 8.5%; pFDP, 6.7%). pFDP was similar
to PP in the attenuation of t-PA-induced fibrinolysis. Most proteins (97%) were
conserved during the freeze-dry process, with higher levels in 12% of pFDP
proteins compared with PP. CONCLUSION: pFDP enhances clot formation and
attenuates hyperfibrinolysis better than NS and albumin and is a potential
alternative to plasma resuscitation in the treatment of hemorrhagic shock.
PMID- 28500653
TI - Blood transfusion in the surgical treatment of adolescent idiopathic scoliosis-a
single-center experience of patient blood management in 210 cases.
AB - BACKGROUND: The surgical treatment of adolescent idiopathic scoliosis can be
associated with substantial blood loss, requiring allogeneic red blood cell (RBC)
transfusion. This study describes the use of RBC and the effect of a standardized
perioperative patient blood management program. STUDY DESIGN AND METHODS:
Patients treated with posterior instrumented fusion were consecutively enrolled
over a 6-year period. Patient blood management strategies were implemented in
2011, including prophylactic tranexamic acid, intraoperative permissive
hypotension, restrictive fluid therapy (including avoidance of synthetic
colloids), restrictive RBC trigger according to institutional standardized
protocol, the use of cell savage, and goal-directed therapy according to
thrombelastography. RESULTS: In total, 210 patients were included. 64 patients
(31%) received RBC transfusions. A decline in the intraoperative rate of RBC
transfusion was observed, from 77% in 2011 to 13% in 2016 (p < 0.001). Patients
in the transfusion group had a significantly larger major curve, lower
preoperative hemoglobin, higher estimated blood loss, and an increased use of
crystalloid volume resuscitation. Multiple logistic regression showed that
significant predictors for RBC transfusion were preoperative hemoglobin level
(odds ratio [OR], 0.40; 95% confidence interval [CI], 0.27-0.57), estimated blood
loss (OR, 1.26; 95% CI, 1.15-1.42), and year of surgery (indicating the effect of
patient blood management) (OR per year, 0.76; 95% CI, 0.58-0.99). CONCLUSION: A
perioperative patient blood management program substantially reduced the need for
RBC transfusion. A preoperative evaluation of anemia is essential to further
minimize transfusion rates.
PMID- 28500654
TI - Altered timing of riboflavin and ultraviolet light pathogen inactivation improves
platelet in vitro quality.
AB - BACKGROUND: The platelet (PLT) storage lesion is in part caused by the collection
and/or production process. Pathogen inactivation (PI) further accelerates its
development leading to a reduced in vitro PLT functionality and hence quality.
Although the treatment of PLT concentrates (PCs) with riboflavin and ultraviolet
light PI should occur within 22 hours of collection, in this study the impact of
treatment timing on in vitro PLT quality was investigated. STUDY DESIGN AND
METHODS: Apheresis PCs were PI treated on the day of production or on Days 1, 3,
or 4 of storage or left untreated as control. A panel of in vitro variables was
used to monitor quality throughout 7-day storage, including metabolism, PLT
activation, and release of microparticles. Changes in phosphorylation profiles of
proteins in the lysate and levels of PLT factor 4, thrombospondin, and epidermal
growth factor (EGF) in the releasate were analyzed by immunoblots or enzyme
linked immunosorbent assay. RESULTS: By Day 7 of storage, units illuminated on
Day 4 showed a smaller impact of the PI process than units treated on the day of
production or one day after on PLT quality such as PLT activation; metabolic
activity; microvesicle and EGF release; and phosphorylation of p38, ERK, and
HSP27. PCs treated on Day 3 of storage displayed an intermediate effect.
CONCLUSION: The timing of PI treatment of PCs influences in vitro PLT quality.
Based on these results, timing recommendations should be reconsidered. If PI is
applied, inventory management in blood banks might improve with a more flexible
collection and treatment regime.
PMID- 28500655
TI - Discovery and validation of candidate host DNA methylation markers for detection
of cervical precancer and cancer.
AB - Human papillomavirus (HPV) testing has been recently introduced as an alternative
to cytology for cervical cancer screening. However, since most HPV infections
clear without causing clinically relevant lesions, additional triage tests are
required to identify women who are at high risk of developing cancer. We
performed DNA methylation profiling on formalin-fixed, paraffin-embedded tissue
specimens from women with benign HPV16 infection and histologically confirmed
cervical intraepithelial neoplasia grade 3, and cancer using a bead-based
microarray covering 1,500 CpG sites in over 800 genes. Methylation levels in
individual CpG sites were compared using a t-test, and results were summarized by
computing p-values. A total of 12 candidate genes (ADCYAP1, ASCL1, ATP10, CADM1,
DCC, DBC1, HS3ST2, MOS, MYOD1, SOX1, SOX17 and TMEFF2) identified by DNA
methylation profiling, plus an additional three genes identified from the
literature (EPB41L3, MAL and miR-124) were chosen for validation in an
independent set of 167 liquid-based cytology specimens using pyrosequencing and
targeted, next-generation bisulfite sequencing. Of the 15 candidate gene markers,
10 had an area under the curve (AUC) of >= 0.75 for discrimination of high grade
squamous intraepithelial lesions or worse (HSIL+) from =0.80, irrespective of methylation detection assay. In
addition to verifying candidate markers from the literature (e.g., SOX1 and
EPB41L3), we identified novel markers that may be considered for detection of
cervical precancer and cancer and warrant further validation in prospective
studies.
PMID- 28500656
TI - A Stable N-Annulated Perylene-Bridged Bisphenoxyl Diradicaloid and the
Corresponding Boron Trifluoride Complex.
AB - Organic pi-extended radicals display unique electronic structures, and could be
used as promising functional materials. However, design and synthesis of stable
radicals are challenging for chemists due to their high reactivity. In this work,
we synthesized a stable N-annulated perylene-bridged bisphenoxyl diradicaloid,
and its complex with Lewis acid boron trifluoride. Their ground-state geometric
and electronic structures were systematically studied by various experimental
methods, including X-ray crystallographic analysis, variable-temperature NMR
spectroscopy, electron-spin resonance spectroscopy (ESR), and superconducting
quantum interference device (SQUID) measurements, supported by density functional
theory. Both were observed as open-shell singlet diradicaloids in the ground
state. The bisphenoxyl diradicaloid demonstrated string features of strong near
infrared (NIR) absorption, closely packed pi-dimer structure in crystals,
amphoteric redox behavior with a small HOMO-LUMO energy band gap, and a rather
small singlet-triplet gap, whereas the complex showed very different
photophysical, electrochemical, and magnetic properties. Our studies provide an
efficient method of making stable diradicaloids by Lewis acid/base complexation.
PMID- 28500658
TI - Evaluation of photoaging scales in an elderly male population.
PMID- 28500657
TI - Modulation of Kv 11.1 (hERG) channels by 5-(((1H-indazol-5-yl)oxy)methyl)-N-(4
(trifluoromethoxy)phenyl)pyrimidin-2-amine (ITP-2), a novel small molecule
activator.
AB - BACKGROUND AND PURPOSE: Activators of Kv 11.1 (hERG) channels have potential
utility in the treatment of acquired and congenital long QT (LQT) syndrome. Here,
we describe a new hERG channel activator, 5-(((1H-indazol-5-yl)oxy)methyl)-N-(4
(trifluoromethoxy)phenyl)pyrimidin-2-amine (ITP-2), with a chemical structure
distinct from previously reported compounds. EXPERIMENTAL APPROACH: Conventional
electrophysiological methods were used to assess the effects of ITP-2 on hERG1a
and hERG1a/1b channels expressed heterologously in HEK-293 cells. KEY RESULTS:
ITP-2 selectively increased test pulse currents (EC50 1.0 MUM) and decreased tail
currents. ITP-2 activated hERG1a homomeric channels primarily by causing large
depolarizing shifts in the midpoint of voltage-dependent inactivation and
hyperpolarizing shifts in the voltage-dependence of activation. In addition, ITP
2 slowed rates of inactivation and made recovery from inactivation faster.
hERG1a/1b heteromeric channels showed reduced sensitivity to ITP-2 and their
inactivation properties were differentially modulated. Effects on midpoint of
voltage-dependent inactivation and rates of inactivation were less pronounced for
hERG1a/1b channels. Effects on voltage-dependent activation and activation
kinetics were not different from hERG1a channels. Interestingly, hERG1b channels
were inhibited by ITP-2. Inactivation-impairing mutations abolished activation by
ITP-2 and led to inhibition of hERG channels. ITP-2 exerted agonistic effect from
extracellular side of the membrane and could activate one of the arrhythmia
associated trafficking-deficient LQT2 mutants. CONCLUSIONS AND IMPLICATIONS: ITP
2 may serve as another novel lead molecule for designing robust activators of
hERG channels. hERG1a/1b gating kinetics were differentially modulated by ITP-2
leading to altered sensitivity. ITP-2 is capable of activating an LQT2 mutant and
may be potentially useful in the development of LQT2 therapeutics.
PMID- 28500659
TI - Insulin sensitivity in relation to fat distribution and plasma adipocytokines
among abusers of anabolic androgenic steroids.
AB - OBJECTIVE: Abuse of anabolic androgenic steroids (AAS) is prevalent among young
men, but information regarding effects on insulin sensitivity and fat
distribution is limited. The objective was to investigate insulin sensitivity in
relation to fat distribution and adipocytokines among current and former AAS
abusers compared with controls. DESIGN: Cross-sectional study among men involved
in recreational strength training. Current and former AAS abusers (n=37 and n=33)
and controls (n=30) volunteered from the community. METHODS: We assessed insulin
sensitivity by Matsuda index (oral glucose tolerance test). Using overnight
fasting blood samples, adiponectin and leptin were measured. Body composition and
fat distribution, including visceral adipose tissue (VAT), were assessed by dual
energy X-ray absorptiometry. RESULTS: Current and former AAS abusers displayed
lower Matsuda index than controls (%-difference (95%CI) from controls, -26% (-45;
-1) and -39% (-55; -18)). Testosterone was markedly higher among current AAS
abusers and subnormal among former AAS abusers compared with controls. Current
AAS abusers displayed higher mean VAT than controls (388 (17) vs 293 (12) cm3 ,
P<.001) whereas body fat %, adiponectin and leptin concentrations were lower. In
contrast, former AAS abusers showed highest leptin concentrations and body fat %.
Multivariate linear regressions identified VAT as independent predictor of lower
Matsuda index among current AAS abusers compared with controls; while body fat %
independently predicted lower Matsuda index among former AAS abusers.
CONCLUSIONS: Both current and former AAS abusers displayed lower insulin
sensitivity which could be mediated by higher VAT and total body fat %,
respectively.
PMID- 28500661
TI - Is mealworm or shrimp allergy indicative for food allergy to insects?
AB - SCOPE: The growing world population is a key driver for the exploration of
sustainable protein sources to ensure food security. Mealworm and other insects
are promising candidates. Previously we found that shrimp allergic patients are
at risk for mealworm allergy, and that mealworm can induce a primary allergy .
This study set out to investigate the allergenic potential of edible insects,
suggested for human consumption by agencies such as WHO/FAO, in both the shrimp
(potentially cross-reactive) and primary mealworm allergic population. The
following insects were studied: mealworm, house cricket, giant mealworm, lesser
mealworm, African grasshopper, large wax moth, and black soldier fly. METHODS AND
RESULTS: Fifteen shrimp (mealworm sensitized or allergic) patients and four
primary mealworm allergic subjects, who participated in previous studies, were
included. All shrimp allergic patients were sensitized to multiple insects with
similar response profiles for all insects tested. Primary mealworm allergic
patients, showed IgE binding to proteins from only a few insects on immunoblot,
although basophil activation test was positive for all tested insects.
CONCLUSION: Shrimp allergic patients are most likely at risk of food allergy to
mealworm and other insects. Primary mealworm allergy does not mean subjects are
likely to react to all insects.
PMID- 28500662
TI - Application of a novel bioreactor for in vivo engineering of pancreas tissue.
AB - Type 1 diabetes is characterized by autoimmune destruction of pancreatic cells.
Organ transplantation is an acceptable treatment for native organ failure.
However, it is associated with several problems due to a number of reasons, such
as the lack of appropriate donors and immunosuppression. In our present study, a
novel model is presented for in vivo recellularization of acellular pancreas by
implanting between the host pancreas and the adjacent omental flap. In this
study, the pancreases were harvested and cannulated via the common bile duct and
then, the scaffolds were acellularized by a detergent-based protocol. After that,
the abdomens of 35 rats were opened and the spleen was extracted with the
adjacent omentum, and placed outside the abdomen. The acellularized scaffold was
stretched over the host pancreas and the omentum was wrapped around it to make a
sandwich-like structure, which was then fixed with Chromic Sutures 6-0 and marked
with Prolene 4-0 on four sides. All samples were biopsied at 14, 30, 60, 90, and
120 days post-transplantation. The result showed marked recellularization of
acellularized pancreas with visible neovascularization and neobeta-cells with
minimal inflammatory response. This study provides a new approach to produces a
normal-like pancreas by allograft transplantation for pancreas tissue
engineering. We observed that in vivo transplantation of acellularized pancreas
can promote recellularization, proliferation, and differentiation by blood
circulation. These findings support that in vivo studies can contribute to
finding faster solutions for the treatment of diabetes.
PMID- 28500660
TI - Association between wrist ratio and carpal tunnel syndrome: Effect modification
by body mass index.
AB - INTRODUCTION: Previous studies have reported higher wrist ratios (WR) related to
carpal tunnel syndrome (CTS) but have not assessed effect modification by obesity
and may have inadequately controlled for confounders. METHODS: Baseline data of a
multicenter prospective cohort study were analyzed. CTS was defined by nerve
conduction study (NCS) criteria and symptoms. RESULTS: Among the 1,206
participants, a square-shaped wrist was associated with CTS after controlling for
confounders (prevalence ratio = 2.27; 95% confidence interval [95% CI], 1.33
3.86). Body mass index (BMI) was a strong effect modifier on the relationship
between WR and both CTS and abnormal NCS results, with normal weight strata of
rectangular versus square wrists = 8.18 (95% CI, 1.63-49.96) and 7.12 (95% CI,
2.19-23.16), respectively. DISCUSSION: A square wrist is significantly associated
with CTS after controlling for confounders. Effect modification by high BMI
masked the eightfold magnitude adjusted relationship seen between WR and CTS
among normal weight participants. Muscle Nerve 56: 1047-1053, 2017.
PMID- 28500663
TI - Obesity and related risk of myeloproliferative neoplasms among israeli
adolescents.
AB - OBJECTIVE: Obesity has been associated with various malignancies, but a clear
association between overweight and myeloproliferative neoplasms (MPN) has not
been established. METHODS: This study assessed the association between adolescent
obesity and future risk for MPN. Data on 2,516,256 Israeli adolescents, who
underwent a compulsory general health examination at ages 16 to 19, between 1967
and 2011, were linked to the National Cancer Registry in this nationwide,
population-based cohort study. Cox proportional hazards models were used to
estimate the hazard ratio (HR) for MPN associated with BMI measured at
adolescence. RESULTS: The mean follow-up of 19.86 +/- 12.15 years reflected
49,977,521 person years, during which 433 examinees developed MPN, primarily
chronic myelogenous leukemia, polycythemia vera, and essential thrombocythemia.
Obesity (BMI >= 95th percentile) in adolescence significantly predicted increased
risk of MPN with HR (adjusted for sex) of 1.81 (95% confidence interval 1.13
2.92, P = 0.014). CONCLUSIONS: Adolescent obesity might be related to an
increased incidence of myeloproliferative neoplasms.
PMID- 28500664
TI - Ligand-Promoted Rhodium(III)-Catalyzed ortho-C-H Amination with Free Amines.
AB - Ligand development for rhodium(III)-catalyzed C-H activation reactions has
largely been limited to cyclopentadienyl (Cp) based scaffolds. 2-Methylquinoline
has now been identified as a feasible ligand that can coordinate to the metal
center of Cp*RhCl to accelerate the cleavage of the C-H bond of N
pentafluorophenylbenzamides, providing a new structural lead for ligand design.
The compatibility of this reaction with secondary free amines and anilines also
overcomes the limitations of palladium(II)-catalyzed C-H amination reactions.
PMID- 28500665
TI - Load-induced changes in the diffusion tensor of ovine anulus fibrosus: A pilot
MRI study.
AB - PURPOSE: To assess the feasibility of diffusion tensor imaging (DTI) for
evaluating changes in anulus fibrosus (AF) microstructure following uniaxial
compression. MATERIALS AND METHODS: Six axially aligned samples of AF were
obtained from a merino sheep disc; two each from the anterior, lateral, and
posterior regions. The samples were mechanically loaded in axial compression
during five cycles at a rate and maximum compressive strain that reflected
physiological conditions. DTI was conducted at 7T for each sample before and
after mechanical testing. RESULTS: The mechanical response of all samples in
unconfined compression was nonlinear. A stiffer response during the first loading
cycle, compared to the remaining cycles, was observed. Change in diffusion
parameters appeared to be region-dependent. The mean fractional anisotropy
increased following mechanical testing. This was smallest in the lateral (2% and
9%) and largest in the anterior and posterior samples (17-25%). The mean average
diffusivity remained relatively constant (<2%) after mechanical testing in the
lateral and posterior samples, but increased (by 5%) in the anterior samples. The
mean angle made by the principal eigenvector with the spine axis in the lateral
samples was 73 degrees and remained relatively constant (<2%) following
mechanical testing. This angle was smaller in the anterior (55 degrees ) and
posterior (47 degrees ) regions and increased by 6-16 degrees following
mechanical testing. CONCLUSION: These preliminary results suggest that axial
compression reorients the collagen fibers, such that they become more
consistently aligned parallel to the plane of the endplates. LEVEL OF EVIDENCE: 1
Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;45:1723-1735.
PMID- 28500666
TI - Bioactivity and mineralization of natural hydroxyapatite from cuttlefish bone and
Bioglass(r) co-sintered bioceramics.
AB - In this study, bioactive hydroxyapatite (HAP)-based bioceramics starting from
cuttlefish bone powders have been prepared and characterized. In particular,
fragmented cuttlefish bone was co-sintered with 30 wt% of Bioglass(r) -45S5 to
synthesize HAP-based powders with enhanced mechanical properties and bioactivity.
Commercial synthetic HAP was treated following the same procedure and used as a
reference. The structure and composition of the bioceramics formulations were
characterized using Fourier transform infrared spectroscopy, X-ray diffraction
and scanning electron microscopy. After the thermal treatment of cuttlefish bone
powder added with 30 wt% Bioglass, new phases with compositions of sodium calcium
phosphate [Na3 Ca6 (PO4 )5 ], beta-tricalcium phosphate [Ca3 (PO4 )] and
amorphous silica were detected. In vitro cell culture studies were performed by
evaluating proliferation, metabolic activity and differentiation of human
osteoblast-like cells (MG63). Scaffolds made with cuttlefish bone powder
exhibited increased apatite deposition, alkaline phosphatase activity and cell
proliferation compared with commercial synthetic HAP. In addition, the ceramic
compositions obtained after the combination with Bioglass(r) further enhanced the
metabolic activity of MG63 cell and promoted the formation of a well-developed
apatite layer after 7 days of incubation in Dulbecco's modified Eagle's medium.
PMID- 28500667
TI - Magnetic resonance neurography and diffusion tensor imaging of the peripheral
nerves in patients with Charcot-Marie-Tooth Type 1A.
AB - INTRODUCTION: Investigation of peripheral neuropathies by magnetic resonance
neurography (MRN) may provide increased diagnostic accuracy when performed in
combination with diffusion tensor imaging (DTI). This study seeks to evaluate DTI
in the detection of neuropathic abnormalities in Charcot-Marie-Tooth type 1A
(CMT1A). METHODS: MRI of the sciatic and tibial nerves, including MRN and DTI,
was prospectively performed in 15 CMT1A patients and 30 healthy controls (HCs).
The following MRI parameters were evaluated and correlated with clinical and
neurophysiological findings: T2-relaxation time, proton spin density (PD) and DTI
(fractional anisotropy [FA] and apparent diffusion coefficient [ADC]). RESULTS:
DTI showed lower FA and higher ADC in CMT1A compared with HCs. T2 relaxation time
showed no difference; however, PD of the sciatic nerve was higher in CMT1A. There
were some close associations between neuropathy severity and MRN-DTI, with the
closest correlation between FA and nerve conduction velocity in the sciatic nerve
(r = 0.76, P < 0.01). DISCUSSION: MRN-DTI evaluation of sciatic and tibial nerves
improves the detection of nerve abnormalities in patients with CMT1A. Muscle
Nerve 56: E78-E84, 2017.
PMID- 28500668
TI - Advanced multivariate data analysis to determine the root cause of trisulfide
bond formation in a novel antibody-peptide fusion.
AB - Product quality heterogeneities, such as a trisulfide bond (TSB) formation, can
be influenced by multiple interacting process parameters. Identifying their root
cause is a major challenge in biopharmaceutical production. To address this
issue, this paper describes the novel application of advanced multivariate data
analysis (MVDA) techniques to identify the process parameters influencing TSB
formation in a novel recombinant antibody-peptide fusion expressed in mammalian
cell culture. The screening dataset was generated with a high-throughput (HT)
micro-bioreactor system (AmbrTM 15) using a design of experiments (DoE) approach.
The complex dataset was firstly analyzed through the development of a multiple
linear regression model focusing solely on the DoE inputs and identified the
temperature, pH and initial nutrient feed day as important process parameters
influencing this quality attribute. To further scrutinize the dataset, a partial
least squares model was subsequently built incorporating both on-line and off
line process parameters and enabled accurate predictions of the TSB concentration
at harvest. Process parameters identified by the models to promote and suppress
TSB formation were implemented on five 7 L bioreactors and the resultant TSB
concentrations were comparable to the model predictions. This study demonstrates
the ability of MVDA to enable predictions of the key performance drivers
influencing TSB formation that are valid also upon scale-up. Biotechnol. Bioeng.
2017;114: 2222-2234. (c) 2017 The Authors. Biotechnology and Bioengineering
Published by Wiley Periodicals, Inc.
PMID- 28500669
TI - Anti-Mullerian hormone signaling is influenced by Follistatin 288, but not 14
other transforming growth factor beta superfamily regulators.
AB - The hypothesis that, in contrast to other transforming growth factor-beta
(TGFbeta) superfamily ligands, the dose-response curve of Anti-Mullerian hormone
(AMH) is unmodulated was tested by examining whether known TGFB superfamily
modulators affect AMH signaling, using a P19/BRE luciferase reporter assay. AMHC
and AMHN,C activated the reporter with an EC50 of approximately 0.5 nM.
Follistatins (FS) produced concentration-dependent increases in AMHC - and AMHN,C
-initiated reporter activity, with FS288 being more potent than FS315; however,
the maximum bioactivity of AMH was not altered by either follistatin. Thirteen
other TGFbeta regulators (Chordin, Chordin-like 1, Chordin-like 2, Differential
screening-selected gene aberrative in neuroblastoma [DAN], Decorin, Endoglin,
Follistatin-like 1, Follistatin-like 3, Follistatin-like 4, Noggin, alpha2
macroglobulin, TGFbeta receptor 3, Von Willebrand factor C domain-containing 2)
had little or no effect. Surface plasmon resonance analysis showed no significant
association between FS288 and AMHC , suggesting that FS288 indirectly regulates
AMH signaling. Activin A, a direct target of FS288, did not itself induce
reporter activity in P19 cells, but did prevent the FS288-induced increase in AMH
signaling. Hence, local concentrations of FS288 and Activin A may influence the
response of some cell types to AMH.
PMID- 28500671
TI - Is the firing rate of motor units in different vastus medialis regions modulated
similarly during isometric contractions?
AB - INTRODUCTION: Previous evidence suggests the fibers of different motor units
reside within distinct vastus medialis (VM) regions. It remains unknown whether
the activity of these motor units may be modulated differently. Herein we assess
the discharge rate of motor units detected proximodistally from the VM to address
this issue. METHODS: Surface electromyograms (EMGs) were recorded proximally and
distally from the VM while 10 healthy subjects performed isometric contractions.
Single motor units were decomposed from surface EMGs. The smoothed discharge
rates of motor units identified from the same and from different VM regions were
then cross-correlated. RESULTS: During low-level contractions, the discharge rate
varied more similarly for distal (cross-correlation peak; interquartile interval:
0.27-0.40) and proximal (0.28-0.52) than for proximodistal pairs of VM motor
units (0.20-0.33; P = 0.006). DISCUSSION: The discharge rates of motor units from
different proximodistal VM regions show less similarity in their variations than
those of pairs of units either distally or proximally. Muscle Nerve 57: 279-286,
2018.
PMID- 28500670
TI - Coupled effects of salt and pressure on catalytic ability of Rhizopus chinensis
lipase.
AB - BACKGROUND: Both high pressure and environmental factors could influence the
catalytic abilities of enzymes. This work investigated coupled effects of
pressure and salts on Rhizopus chinensis lipase (RCL) to provide significant
information for its further applications. RESULTS: The maximum activity of RCL
was observed under 200 MPa at 40 degrees C. The highest activity was achieved at
concentrations of 0.06-0.1 mol L-1 for tested salts. The effect of monovalent
cations on RCL activity followed the Hofmeister series (K+ > Na+ > Li+ ) at 0.1
MPa but the order of Na+ and K+ was changed under 200 MPa. Meanwhile, the effects
of anions did not follow the Hofmeister series. KCl slightly improved the
thermostability of RCL at moderate concentration. At 60 degrees C, LiCl only
stabilised RCL at 0.1 mol L-1 . The pre-transition unfolding point was shifted
from 4.5 to 3.5 mol L-1 with pressure increasing from 0.1 to 600 MPa. In
addition, KCl could not change the lipase's extrinsic fluorescence evolution
versus pressure. CONCLUSION: Pressure and salts could improve catalytic ability
and stability of RCL under appropriate conditions. The effect of high pressure on
RCL was influenced by salts. Meanwhile salts cannot prevent high pressure-induced
damage to RCL. (c) 2017 Society of Chemical Industry.
PMID- 28500673
TI - Uterine tissue aging and adverse reproductive outcomes: New concepts, mechanisms,
and markers.
PMID- 28500672
TI - Telomere length and fetal programming: A review of recent scientific advances.
AB - We sought to synthesize a comprehensive literature review comprising recent
research linking fetal programming to fetal telomere length. We also explored the
potential effects fetal telomere length shortening has on fetal phenotypes.
Utilizing the PubMed database as our primary search engine, we retrieved and
reviewed 165 articles of published research. The inclusion criteria limited the
articles to those that appeared within the last ten years, were pertinent to
humans, and without restriction to language of publication. Our results showed
that socio-demographic factors like age, sex, genetic inheritance, and acquired
disease impact telomere length. Further, we found several maternal
characteristics to be associated with fetal telomere length shortening, and these
include maternal chemical exposure (eg, tobacco smoke), maternal stress during
pregnancy, maternal nutritional and sleeping disorders during pregnancy as well
as maternal disease status. Due to paucity of data, our review could not
synthesize evidence directly linking fetal phenotypes to telomere length
shortening. Although the research summarized in this review shows some
association between determinants of intrauterine programming and fetal telomere
length, there is still significant work that needs to be done to delineate the
direct relationship of telomere attrition with specific fetal phenotypes.
PMID- 28500674
TI - Disseminated cutaneous nocardiosis with ocular involvement.
PMID- 28500675
TI - Counterfactual Plausibility and Comparative Similarity.
AB - Counterfactual thinking involves imagining hypothetical alternatives to reality.
Philosopher David Lewis (1973, 1979) argued that people estimate the subjective
plausibility that a counterfactual event might have occurred by comparing an
imagined possible world in which the counterfactual statement is true against the
current, actual world in which the counterfactual statement is false.
Accordingly, counterfactuals considered to be true in possible worlds
comparatively more similar to ours are judged as more plausible than
counterfactuals deemed true in possible worlds comparatively less similar.
Although Lewis did not originally develop his notion of comparative similarity to
be investigated as a psychological construct, this study builds upon his idea to
empirically investigate comparative similarity as a possible psychological
strategy for evaluating the perceived plausibility of counterfactual events. More
specifically, we evaluate judgments of comparative similarity between episodic
memories and episodic counterfactual events as a factor influencing people's
judgments of plausibility in counterfactual simulations, and we also compare it
against other factors thought to influence judgments of counterfactual
plausibility, such as ease of simulation and prior simulation. Our results
suggest that the greater the perceived similarity between the original memory and
the episodic counterfactual event, the greater the perceived plausibility that
the counterfactual event might have occurred. While similarity between actual and
counterfactual events, ease of imagining, and prior simulation of the
counterfactual event were all significantly related to counterfactual
plausibility, comparative similarity best captured the variance in ratings of
counterfactual plausibility. Implications for existing theories on the
determinants of counterfactual plausibility are discussed.
PMID- 28500676
TI - An evaluation of interdependent and independent group contingencies during the
good behavior game.
AB - The Good Behavior Game (GBG) uses an interdependent group contingency to improve
classroom behavior. Despite the wealth of research on the effectiveness of the
GBG, some teachers may have concerns about their students' abilities to work in
teams, particularly if they have a history of poor social skills. We used an
alternating treatments design to compare the relative effectiveness of the GBG
with interdependent and independent group contingencies in a classroom for
children with emotional and behavioral disorders. Our results showed that both
versions of the GBG reduced verbal disruptions, inappropriate sitting, and off
task behaviors for all children. However, the majority of children preferred the
interdependent arrangement. We discuss how these results may promote more
widespread use of the GBG with children with substantial behavioral challenges.
PMID- 28500678
TI - BGG492 as an adjunctive treatment in patients with partial-onset seizures: A 12
week, randomized, double-blind, placebo-controlled, phase II dose-titration study
with an open-label extension.
AB - OBJECTIVES: To evaluate dose-response relationship of BGG492 as add-on therapy to
1-3 antiepileptic drugs in patients with partial-onset seizures and to
investigate safety and tolerability of BGG492. METHODS: This was a 12-week,
randomized, double-blind, placebo-controlled, phase II dose-titration study (core
study) with a 30-week, flexible-dose, open-label extension. In the core study,
patients were randomized (1:2) to placebo or BGG492 100 mg t.i.d. in cohort 1,
and in cohort 2 patients were randomized (1:4) to placebo or BGG492 150 mg t.i.d.
On completion of the core study, eligible patients entered the extension study.
Primary outcome measures were total partial seizure frequency per 28 days (core
study) and safety and tolerability (extension study). RESULTS: Overall, 93
patients were randomized (150 mg [n = 44]; 100 mg [n = 24]; placebo [n = 25]),
and 81 (87.1%) completed the core study. Fifty-one patients entered and 43
(84.3%) completed the extension study. In the core study, no statistically
significant dose-response trend among the BGG492 treatment groups (100 and 150
mg) was observed at the 4-week double-blind maintenance period (weeks 7-10);
however, there was higher percent reduction in total partial seizure frequency in
the BGG492 150 mg over placebo groups (37.32%; 95% confidence interval [CI]
18.90, 66.95). Dizziness, somnolence, and fatigue were the most common adverse
events (AEs), higher in the BGG492 150 mg group than in the 100 mg and placebo
groups (dizziness: 14 [31.8%] vs. 3 [12.5%] and 1 [4.0%]; somnolence: 7 [15.9%]
vs. 1 [4.2%] and 1 [4.0%]; fatigue: 5 [11.4%] vs. 1 [4.2%] and 1 [4.0%]). During
the open-label extension study, 39 (76.5%) patients on BGG492 had AEs, and the
most commonly experienced AEs were dizziness (14 [27.5%]) and somnolence (9
[17.6%]). SIGNIFICANCE: There was no significant dose-response trend in the
BGG492 treatment groups (100 and 150 mg); however, higher percent reduction over
placebo was observed in the BGG492 150 mg group. Safety and tolerability data
were consistent with the known safety profile for BGG492, and no new safety risks
were identified.
PMID- 28500677
TI - Optimizing the dose in cancer patients treated with imatinib, sunitinib and
pazopanib.
AB - AIM: Fixed dose oral tyrosine kinase inhibitors imatinib, sunitinib and pazopanib
show a high interpatient variability in plasma exposure. A relationship between
plasma exposure and treatment outcome has been established, which supports the
rationale for dose optimization of these drugs. The aim of this study was to
monitor how many patients reached adequate trough levels after therapeutic drug
monitoring-based dose optimization in daily practice. METHODS: A cohort study was
performed in patients treated with imatinib, sunitinib or pazopanib of whom
follow-up drug levels were measured between August 2012 and April 2016. Patients'
characteristics were collected by reviewing electronic patient records. Drug
levels were measured using high-performance liquid chromatography coupled with
tandem mass spectrometry and trough levels were estimated using a predefined
algorithm. Dose interventions were proposed based on trough levels. RESULTS: In
total, 396 trough levels were determined in 109 patients. Median sample frequency
per patient was 3. During the first measurement only 38% of patients showed
trough levels within the predefined target ranges despite standard dosing; 52% of
the patients showed drug levels below and 10% above the target range. In 35 out
of 41 patients (85%) dose interventions led to adequate trough levels.
Eventually, 64% of the total cohort reached adequate trough levels. CONCLUSIONS:
Dose optimization proved an effective tool to reach adequate trough levels in
patients treated with imatinib, sunitinib and pazopanib. The percentage of
patients with adequate trough levels increased from 38 to 64%. Therapeutic drug
monitoring may add to the improvement of efficacy and reduction of toxicity and
costs of these treatments.
PMID- 28500679
TI - Red tattoos, ultraviolet radiation and skin cancer in mice.
AB - Ultraviolet radiation (UVR) induces skin cancer. The combination of UVR and red
tattoos may be associated with increased risk of skin cancer due to potential
carcinogens in tattoo inks. This combination has not been studied previously.
Immunocompetent C3.Cg/TifBomTac hairless mice (n=99) were tattooed on their back
with a popular red tattoo ink. This often used ink is banned for use on humans
because of high content of the potential carcinogen 2-anisidine. Half of the mice
were irradiated with three standard erythema doses UVR thrice weekly. Time to
induction of first, second and third squamous cell carcinoma (SCC) was measured.
All UV-irradiated mice developed SCCs. The time to the onset of the first and
second tumor was identical in the red-tattooed group compared with the control
group (182 vs 186 days and 196 vs 203 days, P=ns). Statistically, the third tumor
appeared slightly faster in the red-tattooed group than in the controls (214 vs
224 days, P=.043). For the second and third tumor, the growth rate was faster in
the red-tattooed group compared with the control (31 vs 49 days, P=.009 and 30 vs
38 days, P=.036). In conclusion, no spontaneous cancers were observed in skin
tattooed with a red ink containing 2-anisidine. However, red tattoos exposed to
UVR showed faster tumor onset regarding the third tumor, and faster growth rate
of the second and third tumor indicating red ink acts as a cocarcinogen with UVR.
The cocarcinogenic effect was weak and may not be clinically relevant.
PMID- 28500680
TI - Rapid detoxification via glutathione S-transferase (GST) conjugation confers a
high level of atrazine resistance in Palmer amaranth (Amaranthus palmeri).
AB - BACKGROUND: Palmer amaranth (Amaranthus palmeri) is an economically troublesome,
aggressive and damaging weed that has evolved resistance to six herbicide modes
of action including photosystem II (PS II) inhibitors such as atrazine. The
objective of this study was to investigate the mechanism and inheritance of
atrazine resistance in Palmer amaranth. RESULTS: A population of Palmer amaranth
from Kansas (KSR) had a high level (160 - 198-fold more; SE +/-21 - 26) of
resistance to atrazine compared to the two known susceptible populations MSS and
KSS, from Mississippi and Kansas, respectively. Sequence analysis of the
chloroplastic psbA gene did not reveal any known mutations conferring resistance
to PS II inhibitors, including the most common Ser264Gly substitution for
triazine resistance. However, the KSR plants rapidly conjugated atrazine at least
24 times faster than MSS via glutathione S-transferase (GST) activity.
Furthermore, genetic analyses of progeny generated from reciprocal crosses of KSR
and MSS demonstrate that atrazine resistance in Palmer amaranth is a nuclear
trait. CONCLUSION: Although triazine resistance in Palmer amaranth was reported
more than 20 years ago in the USA, this is the first report elucidating the
underlying mechanism of resistance to atrazine. The non-target-site based
metabolic resistance to atrazine mediated by GST activity may predispose the
Palmer amaranth populations to have resistance to other herbicide families, and
the nuclear inheritance of the trait in this dioecious species further
exacerbates the propensity for its rapid spread. (c) 2017 Society of Chemical
Industry.
PMID- 28500681
TI - Comparison of Time to First Dose of Oral Morphine in the Treatment of Neonatal
Abstinence Syndrome.
AB - OBJECTIVE: To compare time to first dose of oral morphine used in the treatment
of neonatal abstinence syndrome (NAS) in a neonatal intensive care unit (NICU)
versus a special care nursery (SCN) setting. METHODS: A retrospective chart
review was completed of patient data from two community hospitals in a single
health network. Infants born at either facility between January 2013 and August
2015 were eligible for inclusion in the study if treated for NAS with a course of
oral morphine. The primary outcome was time from birth to first dose of oral
morphine. Secondary outcomes included details about the morphine treatment
course, length of stay, and complications from NAS. RESULTS: A total of 54
patients (19 NICU patients and 35 SCN patients) fulfilled inclusion criteria for
the study. The primary outcome of median time from birth to first dose of oral
morphine did not differ between the two groups (42.5 hrs [NICU] vs 43 hrs [SCN],
p=0.53). No significant differences were found between the morphine regimens used
in the two units. The median length of hospital stay (27 days [NICU] vs 26 days
[SCN], p=0.66) and median length of NICU/SCN stay (26 days [NICU] vs 23 days
[SCN], p=0.75) were not statistically significantly different. Time between
transfer to the NICU or SCN and administration of the first dose of oral morphine
was significantly shorter in the SCN setting (28 hrs [NICU] vs 4 hrs [SCN],
p=0.009). CONCLUSIONS: This study found that infants treated for NAS had similar
treatment in an NICU and an SCN. No difference was observed in time from birth to
initiation of medication therapy. In addition, no differences were seen in all
but one marker for quality of care including length of stay and cumulative
morphine dose. Infants treated for NAS, whether in an NICU or SCN setting, can
receive similar treatment and comparable outcomes.
PMID- 28500682
TI - Red blood cell transfusions during sickle cell anemia vaso-occlusive crises: a
report from the magnesium in crisis (MAGiC) study.
AB - BACKGROUND: Little is known about red blood cell (RBC) transfusion practices for
children hospitalized for a sickle cell vaso-occlusive pain crisis (VOC). We
hypothesized that transfusion would be associated with the development of acute
chest syndrome (ACS), lower hemoglobin (Hb) concentration, and lack of
hydroxyurea therapy. STUDY DESIGN AND METHODS: This is a secondary analysis of
all children admitted for a sickle cell pain crisis enrolled in the Magnesium in
Crisis (MAGiC) randomized trial; all had HbSS or S-beta0 thalassemia. ACS
development and transfusion administration were prospectively collected during
the parent trial. All Hb values during the hospitalization were recorded, as was
parent report of child receiving hydroxyurea. Relative risks (RRs) of transfusion
were compared between groups. RESULTS: Of 204 enrolled children, 40 (19.6%)
received a transfusion. Of the 30 children who developed ACS, 22 (73.3%) received
transfusions compared to 18 of 174 (10.3%) without ACS: the RR of transfusion in
children with ACS was 7.1 (95% confidence interval [CI], 4.4-11.5). Among those
without ACS, the lowest Hb was most strongly associated with transfusions: RR was
3.1 (95% CI 2.0 - 4.7) for each 1 g/dL decrease in lowest Hb. In a binary
recursive partitioning model for those without ACS, a lowest recorded Hb level of
less than 6.3 g/dL was significantly associated with transfusion during admission
(p < 0.01). Hydroxyurea use was not associated with transfusions in any analysis.
CONCLUSION: ACS increased the RR of transfusion in children hospitalized for VOC
sevenfold. In children without ACS, transfusion was associated with lowest Hb
concentration, particularly Hb concentration of less than 6.3 g/dL.
PMID- 28500683
TI - Induction of telomere-mediated chromosomal truncation and behavior of truncated
chromosomes in Brassica napus.
AB - Engineered minichromosomes could be stably inherited and serve as a platform for
simultaneously transferring and stably expressing multiple genes. Chromosomal
truncation mediated by repeats of telomeric sequences is a promising approach for
the generation of minichromosomes. In the present work, direct repetitive
sequences of Arabidopsis telomere were used to study telomere-mediated truncation
of chromosomes in Brassica napus. Transgenes containing alien Arabidopsis
telomere were successfully obtained, and Southern blotting and fluorescence in
situ hybridization (FISH) results show that the transgenes resulted in successful
chromosomal truncation in B. napus. In addition, truncated chromosomes were
inherited at rates lower than that predicted by Mendelian rules. To determine the
potential manipulations and applications of the engineered chromosomes, such as
the stacking of multiple transgenes and the Cre/lox and FRT/FLP recombination
systems, both amenable to genetic manipulations through site-specific
recombination in somatic cells, were tested for their ability to undergo
recombination in B. napus. These results demonstrate that alien Arabidopsis
telomere is able to mediate chromosomal truncation in B. napus. This technology
would be feasible for chromosomal engineering and for studies on chromosome
structure and function in B. napus.
PMID- 28500685
TI - Analysis of serum markers of cellular immune activation in patients with bullous
pemphigoid.
AB - Experimental models of bullous pemphigoid (BP), the most frequent subepidermal
autoimmune bullous disease, revealed that the immune response leading to blister
formation represents an incompletely understood complex process involving
different inflammatory cells. In contrast to previous reports commonly focusing
on limited molecular and cellular phenotypes of the disease, the aim of this
study was to investigate a broad spectrum of markers of cellular immune
activation in patients with BP. We found that serum levels of soluble CD4,
myeloperoxidase, S100A12, eosinophil cationic protein and soluble P-selectin were
significantly elevated in patients with active BP compared with normal controls.
Mast cell tryptase and neopterin serum levels significantly decreased at the time
of clinical remission of the patients. Additionally, serum concentrations of
soluble IL-2 receptor, mast cell tryptase and soluble P-selectin were
significantly associated with levels of circulating anti-BP180 autoantibodies.
Our findings confirm and extend previous reports suggesting some concomitant
involvement of a panel of molecules representative for a wide spectrum of
cellular players (T cells, mast cells, neutrophils, eosinophils, macrophages and
platelets) orchestrating the inflammatory reaction in BP. These data may favour
the employment of broad-spectrum or combined immunosuppressants, potentially
together with an anticoagulant treatment, over cell- or molecule-specific
targeted therapy in patients with this disorder.
PMID- 28500684
TI - Impact of Roux-en-Y gastric bypass surgery on appetite, alcohol intake behaviors,
and midbrain ghrelin signaling in the rat.
AB - OBJECTIVE: Roux-en-Y gastric bypass (RYGB) surgery reduces appetite and
stimulates new onset alcohol misuse; however, the genesis of these behavioral
changes is unclear. This study is hypothesized that new onset alcohol intake is a
behavioral adaptation that occurs secondary to reduced appetite and correlates
with altered central ghrelin signaling. METHODS: Hedonic high-fat diet (HFD)
intake was evaluated prior to the assessment of alcohol intake behaviors in RYGB
and control rats. Measurements were also taken of circulating ghrelin and ghrelin
receptor (GHSR) regulation of neuronal firing in ventral tegmental area (VTA)
dopamine (DA) neurons. RESULTS: RYGB rats displayed reduced HFD intake relative
to controls. Sham and RYGB rats consumed more alcohol and preferred lower
concentrations of alcohol, whereas only RYGB rats escalated alcohol intake during
acute withdrawal. Remarkably, GHSR activity, independent of peripheral ghrelin
release, set the tonic firing of VTA DA neurons, a response selectively
diminished in RYGB rats. CONCLUSIONS: This study indicates that gut manipulations
lead to increased alcohol intake, whereas RYGB promotes behaviors that may
maintain alcohol misuse. Reductions in hedonic feeding and diminished GHSR
control of VTA firing further distinguish gut manipulation from complete bypass
and present a potential mechanism linking reduced appetite with alcohol misuse
after RYGB surgery.
PMID- 28500686
TI - Factors predicting overall response and overall survival in hepatocellular
carcinoma patients undergoing balloon-occluded transcatheter arterial
chemoembolization: A retrospective cohort study.
AB - AIM: This study aimed to investigate the factors predicting overall response and
overall survival in hepatocellular carcinoma patients undergoing balloon-occluded
transcatheter arterial chemoembolization (B-TACE). METHODS: Sixty-six patients
treated with B-TACE at a Japanese tertiary referral hospital between January 2011
and August 2015 were included in this retrospective cohort study. RESULTS: The
overall response was classified as complete response, partial response, stable
disease, and progressive disease in 35 (53.0%), 7 (10.6%), 13 (19.7%), and 11
(16.7%) patients, respectively. The response rate was 63.6%, and the disease
control rate was 83.3%. The number of tumors (hazard ratio [HR], 4.44; 95%
confidence interval [CI], 1.26-15.7; P = 0.021) and alpha-fetoprotein level (HR,
11.40; 95% CI, 2.75-46.9; P < 0.001) were significantly associated with the tumor
response in a multivariate analysis. The 1-, 2-, and 3-year survival rates were
76.8% (95% CI, 64.5-85.3%), 57.3% (95% CI, 42.3-69.7%), and 46.7% (95% CI, 30.7
61.2%), respectively. The median survival time was 902 days. Albumin (>=3.4 g/dL)
(HR, 0.28; 95% CI, 0.12-0.63; P = 0.002) and overall response (complete response
and partial response) (HR, 0.33; 95% CI, 0.16-0.71; P = 0.004) were factors
significantly associated with overall survival in a multivariate analysis. No
mortalities were observed, but biloma requiring percutaneous transhepatic biliary
drainage occurred in one patient (1.5%). CONCLUSION: Balloon-occluded
transcatheter arterial chemoembolization may exert a good antitumor effect and
result in good overall survival in select hepatocellular carcinoma patients.
PMID- 28500687
TI - Epidemiological analysis and follow-up of human rhinovirus infection in children
with asthma exacerbation.
AB - To determine the prevalence of human rhinovirus (HRV) infection in children with
acute asthma exacerbations, investigation of HRV viral load and severity of
asthma exacerbations is also required. Nasopharyngeal aspirates and swabs were
collected and assessed for respiratory viruses. HRV-positive samples were
sequenced to identify types and determine viral load. Outpatients with asthma
exacerbations underwent follow-up evaluations, their swabs were collected and
clinical outcomes were recorded at their next clinic visit 4 weeks later. One
hundred forty-three inpatients and 131 outpatients, including 88 patients with
asthma exacerbations and 43 controls with stable asthma were recruited. HRV-A was
mainly detected in September and February (45.5% and 33.3%, respectively), while
HRV-C was mainly detected in November and April (70.0% and 55.6%, respectively).
HRV-C was the primary type and was primarily found in inpatients with severe
asthma exacerbations. HRV-A viral load in the group of inpatients with severe
exacerbations was higher than in the mild and moderate groups (P < 0.001 and P =
0.022). The HRV-A viral load of both inpatients and outpatients was higher than
that of HRV-C (P < 0.001 and P = 0.036). The main genotypes were HRV-C53 and HRV
A20 among inpatients, and this genotype caused more severe clinical
manifestations. HRV persisted for no more than 4 weeks, and their symptoms or
signs of disease were well-controlled well. HRV-C was most frequently detected in
asthma exacerbations. HRV-A with high viral load led to severe asthma
exacerbations.
PMID- 28500688
TI - Fennel (Foeniculum vulgare Mill. subsp. piperitum) florets, a traditional
culinary spice in Italy: evaluation of phenolics and volatiles in local
populations, and comparison with the composition of other plant parts.
AB - BACKGROUND: Wild fennel (Foeniculum vulgare Mill. subsp. piperitum) florets are
used as a typical spice in central and southern Italy. Although fennel
(Foeniculum vulgare Mill.), belonging to the Apiaceae (syn. Umbelliferae) family,
is a well-known vegetable and aromatic plant, whose main phytochemical compounds
have been extensively analysed and investigated as flavouring agents and for
their putative health promoting functions, its florets have not been specifically
considered up to now. Therefore, the volatile and phenolic composition of florets
from an Italian wild fennel crop was determined at different developmental
stages, and compared to that of leaves and fruits. Moreover, florets of nine
Italian wild fennel populations of different geographical origin from northern
central Italy were also analysed. RESULTS: The total phenolic amount increased
from leaves to florets, reaching its highest value in early florets, at 58 012 mg
kg-1 of dry matter (DM), then constantly decreased in fruits. In florets of wild
populations, phenolics ranged from 6666 to 43 368 mg kg-1 DM. The total amount of
volatile compounds was more than twice higher in florets (21 449 mg kg-1 DM) than
in leaves (10 470 mg kg-1 DM), reaching its highest value in fruits (50 533 mg kg
1 DM). Estragole and trans-anethole were the main compounds of the volatile
fraction. Total volatiles ranged from 24 367 to 60 468 mg kg-1 DM in florets of
local populations. CONCLUSION: Significant changes in the total amount and
profile of both phenolic and volatile compounds occurred during plant
development. The consistent increase of estragole at later developmental stages
supported the claim of different sensory properties of florets and fruits.
Geographical origin significantly affected phenolic and volatile composition of
wild fennel florets. (c) 2017 Society of Chemical Industry.
PMID- 28500690
TI - Tumour necrosis factor receptor-associated periodic syndrome mimicking chronic
spontaneous urticaria.
PMID- 28500689
TI - Blockade of hedgehog pathway is required for the protective effects of magnesium
isoglycyrrhizinate against ethanol-induced hepatocyte steatosis and apoptosis.
AB - Alcoholic liver disease (ALD), characterized by excessive deposition of lipids in
hepatocytes, causes heavy health burden personally and socially. Mechanistically,
hedgehog signaling was activated during the development of ALD, and exerted
compelling role in regulating lipometabolism. The current promising intervention
strategy is inhibition of lipid accumulation and apoptosis in hepatocytes.
Magnesium isoglycyrrhizinate (MgIG) has been widely used in various liver
diseases for its good hepatoprotective activities. However, the role of MgIG in
ALD has not been elucidated. Therefore, this study was aimed to explore the role
of MgIG and further identify the potential mechanisms. We found for the first
time that MgIG reduced lipid accumulation, including triglyceride, and total
cholesterol, probably via inducing peroxisome proliferator-activated receptor
alpha and inhibiting sterol regulatory element-binding protein-1c. Further, MgIG
alleviated ethanol-induced oxidative stress, evidenced by reduced abundance of
reactive oxygen species and increased levels of glutathione, superoxide
dismutase, and mitochondrial transmembrane potential. Besides, MgIG protected
hepatocytes from ethanol-induced apoptosis. In addition, MgIG dose-dependently
suppressed hedgehog signaling. Of note was that disruption of hedgehog signaling
could mimic the effects of MgIG, whereas activation of hedgehog signaling
abrogated the effects of MgIG. These findings suggested that MgIG prevented
ethanol-induced hepatocyte steatosis and apoptosis via a hedgehog signaling
inhibition-dependent mechanism. (c) 2017 IUBMB Life, 69(7):540-552, 2017.
PMID- 28500691
TI - An Interventional Study Using Cell-Mediated Immunity to Personalize Therapy for
Cytomegalovirus Infection After Transplantation.
AB - Cell-mediated immune responses predict clinical cytomegalovirus (CMV) events but
have not been adopted into routine practice due to lack of interventional
studies. Our objective was to demonstrate the safety and feasibility of early
discontinuation of antivirals based on the real-time measurement of CMV-specific
cell-mediated immunity (CMI) in patients with CMV viremia. Transplant patients
were enrolled at the onset of CMV viremia requiring antiviral therapy. CD8 T cell
responses were determined using the Quantiferon-CMV assay, and results were used
to guide subsequent management. A total of 27 patients (median viral load at
onset 10 900 International Units/mL) were treated until viral load negative. At
end of treatment, 14/27 (51.9%) had a positive CMV-CMI response and had
antivirals discontinued. The remaining 13/27 (48.1%) patients had a negative CMV
CMI response and received 2 months of secondary antiviral prophylaxis. In those
with a positive CMI and early discontinuation of antivirals, only a single
patient experienced a low-level asymptomatic recurrence. In contrast, recurrence
was observed in 69.2% of CMI-negative patients despite more prolonged antivirals
(p = 0.001). In conclusion, this is the first study to demonstrate the
feasibility and safety of real-time CMV-specific CMI assessment to guide changes
to the management of CMV infection.
PMID- 28500693
TI - The clinical spectrum of xanthomatous lesions of the eyelids.
AB - Yellowish papules, nodules, or plaques, namely "xanthomatous" lesions, may be
seen on the eyelids in the course of various disorders. The prototype is
"xanthelasma palpebrarum" (XP) that is localized only to the eyelids and may be
associated with hyperlipidemia. On the other hand, different types of
normolipemic disorders may also cause xanthomatous eyelid lesions. Among these,
Langerhans cell histiocytosis, diffuse normolipemic xanthoma, and non-Langerhans
cell histiocytoses (papular xanthoma, juvenile xanthogranuloma, xanthoma
disseminatum, adult-onset xanthogranuloma, adult-onset asthma and periocular
xanthogranuloma, necrobiotic xanthogranuloma, Erdheim-Chester disease, Rosai
Dorfman disease, and reticulohistiocytosis) can be listed. The eyelid findings of
this heterogeneous group of disorders are challenging to differentiate from each
other due to common clinical aspects that may even sometimes mimic XP.
Nodularity, induration, ulceration, diffuse eyelid involvement, and extension
from eyelids to the neighboring skin may represent the clinical features of
xanthomatous lesions other than XP. It is necessary to obtain a thorough history
and exclude XP and then perform detailed dermatological and systemic examination,
biopsy for histopathologic confirmation, and appropriate specific imaging
screens. As some of the conditions may be associated with other systemic
disorders, especially malignancies, the differentiation of xanthomatous eyelid
lesions has a critical importance, and clinical signs can be guiding.
PMID- 28500692
TI - Toll-like receptor 4 mediates fat, sugar, and umami taste preference and food
intake and body weight regulation.
AB - OBJECTIVE: Immune and inflammatory pathways play important roles in the
pathogenesis of metabolic disorders. This study investigated the role of toll
like receptor 4 (TLR4) in orosensory detection of dietary lipids and sugars.
METHODS: Taste preferences of TLR4 knockout (KO) and wild-type (WT) male mice
under a standard and a high-fat, high-sugar diet were assessed with two-bottle
tests. Gene expression of taste signaling molecules was analyzed in the tongue
epithelium. The role of TLR4 in food intake and weight gain was investigated in
TLR4 KO and WT mice fed a high-fat and high-sugar diet for 12 weeks. RESULTS:
Compared to WT mice, TLR4 KO mice showed reduced preference for lipids, sugars,
and umami in a two-bottle preference test. The altered taste perception was
associated with decreased levels of key taste regulatory molecules in the tongue
epithelium. TLR4 KO mice on a high-fat and high-sugar diet consumed less food and
drink, resulting in diminished weight gain. CONCLUSIONS: TLR4 signaling promotes
ingestion of sugar and fat by a mechanism involving increased preference for such
obesogenic foods.
PMID- 28500694
TI - Trends of Neonatal Abstinence Syndrome Epidemic and Maternal Risk Factors in
Florida.
AB - OBJECTIVE: This study aimed to examine secular trends of (i) maternal
prescription opioid use in late pregnancy, (ii) neonatal abstinence syndrome
(NAS) stratified by late maternal prescription opioid use, and (iii) maternal
risk factors among NAS deliveries. METHODS: Women with a live birth who were
enrolled 90 days before and 30 days after delivery in Florida Medicaid Analytic
Extract billing records linked to birth certificates from 2000 to 2010 were
identified for the study. Changes in the annual prevalence of prescription opioid
use during pregnancy were tested with use of the Cochran-Armitage trend test.
Temporal trends of NAS deliveries were estimated with the use of Poisson
regression and stratified by prescription opioid exposure in the last 90 days of
pregnancy in the study period. To identify contributors to the increase in NAS
cases, variations in prevalence of opioid dispensing, tobacco use, antidepressant
use, and substance use disorder among NAS and non-NAS deliveries were examined.
RESULTS: There were 41,968 (9.4%) deliveries exposed to at least one opioid
prescription in late pregnancy, and this rate remained stable from 2000 to 2010.
Among prescription opioid-exposed deliveries, frequency of NAS increased from 1.6
to 25.2 per 1000 live births during the study period (p<0.05). Although the
prevalence of maternal use of prescription opioid, tobacco, and antidepressants
remained stable among NAS deliveries from 2000 to 2010, the prevalence of
substance use disorder diagnoses increased substantially from 38.9% in 2000 to
67.9% in 2006 (p<0.05). CONCLUSIONS: The prevalence of NAS increased dramatically
whereas the prevalence of major risk factors, including maternal prescription
opioid use, remained stable in Florida between 2000 and 2010. The increase in
substance use disorder may be responsible for the sharp increase in NAS
deliveries.
PMID- 28500696
TI - A Simple Preparation Method for Phytochromobilin.
AB - Phytochromobilin (PPhiB), the chromophore of plant phytochromes, is difficult to
isolate because phytochromes occur at very low concentrations in plants. It is,
therefore, frequently replaced in plant phytochrome studies by phycocyanobilin,
which is abundant in cyanobacteria. PPhiB is also an attractive chromophore for
far-red emitting chromoproteins. In this work, we design and optimize a simple
method to efficiently isolate useful quantities of PPhiB: The chromophore is
generated in Escherichia coli and transiently bound to a tailored chromophore
binding domain of ApcE2, the apo-protein of a core-membrane linker, from which it
can subsequently be released. The ease and effectiveness of this method hinges
not only on the enhanced biosynthesis of PPhiB in the presence of the ApcE2
construct from Synechococcus sp. PCC7335, but also on the noncovalent binding of
the pigment to its apo-protein. The isolated PPhiB was successfully incorporated
into phytochrome-related assemblies, and furthermore, the noncovalently bound
PPhiB could be transferred directly from the ApcE2 construct to the apo-proteins
of phytochromes, cyanobacteriochromes and phycobiliproteins, without loss of
relevant biological activity.
PMID- 28500695
TI - Clinical characteristics and survival of systemic sclerosis patients with
pulmonary hypertension and elevated wedge pressure: Observations from the PHAROS
cohort.
AB - BACKGROUND AND OBJECTIVE: Systemic sclerosis (SSc) is a complex autoimmune
disease commonly associated with pulmonary hypertension (PH). When associated
with elevated pulmonary artery wedge pressure (PAWP), pulmonary artery pressure
(PAP) is either in-proportion (post-capillary PH) or higher than expected
(combined PH) relative to the increased PAWP. METHODS: Patients from the PHAROS
registry (a prospective observational cohort of SSc-PH patients) who had mean PAP
>= 25 and PAWP > 15 on right heart catheterization were stratified based on
diastolic pressure gradient (DPG). Kaplan-Meier analysis was performed to compare
survival and PH-related hospitalization. Baseline factors were compared between
patients dying and those who survived using Cox regression analysis. RESULTS: A
total of 59 patients were included, of whom 21 (36%) patients were classified as
combined PH and 38 (64%) had post-capillary PH. No baseline characteristics were
significantly different between the two groups. There were no differences in
survival or PH-related hospitalization between the groups. The only baseline
factor independently associated with death was lower 6-min walk distance (6MWD)
(hazard ratio (HR): 1.33 per 25 m decrease, 95% CI: 1.11-1.59, P = 0.002). PH
specific medications were started during follow-up in significantly more patients
in the combined PH group compared with the post-capillary group (86% vs 50%, P =
0.01). CONCLUSION: Outcomes were similar between SSc patients with post-capillary
PH and combined pre- and post-capillary PH. 6MWD at baseline can predict risk for
death in SSc patients with PH and an elevated PAWP. More patients with combined
PH were started on PH-specific medications, and the clinical benefit of treating
this subgroup specifically in SSc patients needs further exploration.
PMID- 28500697
TI - Light-Induced Conformational Changes in the Plant Cryptochrome Photolyase
Homology Region Resolved by Selective Isotope Labeling and Infrared Spectroscopy.
AB - Plant cryptochromes are photoreceptors that regulate flowering, circadian rhythm
and photomorphogenesis in response to blue and UV-A light. It has been
demonstrated that the oxidized flavin cofactor is photoreduced to the neutral
radical state via separate electron and proton transfer. Conformational changes
have been found in the C-terminal extension, but few studies have addressed the
changes in secondary structure in the sensory photolyase homology region (PHR).
Here, we investigated the PHR of the plant cryptochrome from the green alga
Chlamydomonas reinhardtii by light-induced infrared difference spectroscopy in
combination with global 13 C and 15 N isotope labeling. Assignment of the signals
is achieved by establishing a labeling strategy for cryptochromes that preserves
the flavin at natural abundance. We demonstrate by UV/vis spectroscopy that the
integrity of the sample is maintained and by mass spectrometry that the global
labeling was highly efficient. As a result, difference bands are resolved at full
intensity that at natural abundance are compensated by the overlap of flavin and
protein signals. These bands are assigned to prominent conformational changes in
the PHR by blue light illumination. We postulate that not only the partial
unfolding of the C-terminal extension but also changes in the PHR may mediate
signaling events.
PMID- 28500698
TI - Phytochromes from Agrobacterium fabrum.
AB - Agrobacterium fabrum is a widely used model bacterium for gene transfer from pro-
to eukaryote, for genetics and metabolism. The phytochrome system of
Agrobacterium, encompassing the two phytochromes Agp1 and Agp2, has provided deep
insight into phytochrome action in a bacterial organism. This review summarizes
recent results on phytochrome evolution, phytochrome regulation of conjugation
and plant infection and biochemical studies including the crystal structure of
Agp1-PCM, the photosensory core module of Agp1.
PMID- 28500699
TI - Distinctive Properties of Dark Reversion Kinetics between Two Red/Green-Type
Cyanobacteriochromes and their Application in the Photoregulation of cAMP
Synthesis.
AB - Cyanobacteriochromes (CBCRs) are photoreceptors that bind to a linear
tetrapyrrole within a conserved cGMP-phosphodiesterase/adenylate cyclase/FhlA
(GAF) domain and exhibit reversible photoconversion. Red/green-type CBCR GAF
domains that photoconvert between red- (Pr) and green-absorbing (Pg) forms occur
widely in various cyanobacteria. A putative phototaxis regulator, AnPixJ,
contains multiple red/green-type CBCR GAF domains. We previously reported that
AnPixJ's second domain (AnPixJg2) but not its fourth domain (AnPixJg4) shows
red/green reversible photoconversion. Herein, we found that AnPixJg4 showed Pr-to
Pg photoconversion and rapid Pg-to-Pr dark reversion, whereas AnPixJg2 showed a
barely detectable dark reversion. Site-directed mutagenesis revealed the
involvement of six residues in Pg stability. Replacement at the Leu294/Ile660
positions of AnPixJg2/AnPixJg4 showed the highest influence on dark reversion
kinetics. AnPixJg2_DR6, wherein the six residues of AnPixJg2 were entirely
replaced with those of AnPixJg4, showed a 300-fold faster dark reversion than
that of the wild type. We constructed chimeric proteins by fusing the GAF domains
with adenylate cyclase catalytic regions, such as AnPixJg2-AC, AnPixJg4-AC and
AnPixJg2_DR6-AC. We detected successful enzymatic activation under red light for
both AnPixJg2-AC and AnPixJg2_DR6-AC, and repression under green light for
AnPixJg2-AC and under dark incubation for AnPixJg2_DR6-AC. These results provide
platforms to develop cAMP synthetic optogenetic tools.
PMID- 28500701
TI - Editorial (2017, issue 3).
PMID- 28500700
TI - Influence of Heterogeneity on the Ultrafast Photoisomerization Dynamics of Pfr in
Cph1 Phytochrome.
AB - Photoisomerization of a protein-bound chromophore is the basis of light sensing
and signaling in many photoreceptors. Phytochrome photoreceptors can be
photoconverted reversibly between the Pr and Pfr states through
photoisomerization of the methine bridge between rings C and D. Ground-state
heterogeneity of the chromophore has been reported for both Pr and Pfr. Here, we
report ultrafast visible (Vis) pump-probe and femtosecond polarization-resolved
Vis pump-infrared (IR) probe studies of the Pfr photoreaction in native and 13
C/15 N-labeled Cph1 phytochrome with unlabeled PCB chromophore, demonstrating
different S0 substates, Pfr-I and Pfr-II, with distinct IR absorptions,
orientations and dynamics of the carbonyl vibration of ring D. We derived time
constants of 0.24 ps, 0.7 ps and 6 ps, describing the complete initial
photoreaction. We identified an isomerizing pathway with 0.7 ps for Pfr-I, and
silent dynamics with 6 ps for Pfr-II. We discuss different origins of the Pfr
substates, and favor different facial orientations of ring D. The model provides
a quantum yield for Pfr-I of 38%, in line with ~35% ring D rotation in the
electronic excited state. We tentatively assign the silent form Pfr-II to a dark
adapted state that can convert to Pfr-I upon light absorption.
PMID- 28500702
TI - Bacterial Photosensory Proteins and Their Role in Plant-pathogen Interactions.
AB - Light is an important environmental signal for almost all living organisms. The
light perception is achieved by photoreceptor proteins. As can be observed from
the great number of bacterial genomes sequenced, plant pathogenic bacteria encode
for a large number of photoreceptor proteins. The physiological implications of
these photoreceptors are still poorly characterized. However, recent studies
revealed the participation of these photosensory proteins in the pathogenic
process. Here, we summarize what is known about these proteins and their role
during the virulence process, concluding that the light environment modulates the
plant-pathogen interaction.
PMID- 28500703
TI - Excitation Energies of Canonical Nucleobases Computed by Multiconfigurational
Perturbation Theories.
AB - In this computational work, we assessed the performance of ab initio
multireference (MR) methods for the calculation of vertical excitation energies
of five nucleobases: adenine, guanine, cytosine, thymine and uracil. In total, we
have studied 38 singlet and 30 triplet excited states. Where possible we used the
multireference configuration interaction (MRCI) method as a reference for various
flavors of multireference perturbation theory to second order. In particular, we
have benchmarked CASPT2, NEVPT2 and XMCQDPT2. For CASPT2, we have analyzed the
single-state, multistate (MS) and extended MS variants. In addition, we have
assessed the effect of the ionization potential electron affinity (IPEA) shift.
For NEVPT2, we have used the partially and the strongly contracted variants.
Further, we have tested the commonly used RI-CC2, RI-ADC2 and EOM-CCSD methods.
Generally, we observe the following trends for singlet excited states: NEVPT2 is
the closest MR method to MRCISD+Q, closely followed by CASPT2 with the default
IPEA shift. The same trend is observed for triplet states, although NEVPT2 and
CASPT2-IPEA are getting closer. Interestingly, the n, pi* singlet excited states
were described more accurately than pi, pi* excited states, while for triplet
states the trend is inverted except for NEVPT2. This work is an important
benchmark for future photochemical investigations.
PMID- 28500704
TI - Meta-Analysis of the Transcriptome Reveals a Core Set of Shade-Avoidance Genes in
Arabidopsis.
AB - The presence of neighboring vegetation modifies the light input perceived by
photo-sensory receptors, initiating a signaling cascade that adjusts plant growth
and physiology. Thousands of genes can change their expression during this
process, but the structure of the transcriptional circuit is poorly understood.
Here we present a meta-analysis of transcriptome data from Arabidopsis thaliana
exposed to neighbor signals in different contexts, including organs where growth
is promoted or inhibited by these signals. We identified a small set of genes
that consistently and dynamically respond to neighbor light signals. This group
is also affected by light during de-etiolation and day/night cycles. Among these
genes, many of those with positive response to neighbor signals are binding
targets of PHYTOCHROME-INTERACTING FACTORS (PIFs) and function as transcriptional
regulators themselves, but none of these features is observed among those with
negative response to neighbor signals. Changes. in neighbor signals can mimic the
transcriptional signature of auxin, gibberellins, brassinosteroid, abscisic acid,
ethylene, jasmonic acid and cytokinin but in a context-dependent manner. We
propose the existence of a small core set of genes involved in downstream
communication of PIF signaling status and in the control of light sensitivity and
chloroplast metabolism.
PMID- 28500705
TI - Integration of Temperature and Blue-Light Sensing in Acinetobacter baumannii
Through the BlsA Sensor.
AB - BlsA is a BLUF photoreceptor present in Acinetobacter baumannii, responsible for
modulation of motility, biofilm formation and virulence by light. In this work,
we have combined physiological and biophysical evidences to begin to understand
the basis of the differential photoregulation observed as a function of
temperature. Indeed, we show that blsA expression is reduced at 37 degrees C,
which correlates with negligible photoreceptor levels in the cells, likely
accounting for absence of photoregulation at this temperature. Another point of
control occurs on the functionality of the BlsA photocycle itself at different
temperatures, which occurs with an average quantum yield of photoactivation of
the signaling state of 0.20 +/- 0.03 at 15 degrees C < T < 25 degrees C, but is
practically inoperative at T > 30 degrees C, as a result of conformational
changes produced in the nanocavity of FAD. This effect would be important when
the photoreceptor is already present in the cell to avoid almost instantaneously
further signaling process when it is no longer necessary, for example under
circumstances of temperature changes possibly faced by the bacteria. This complex
interplay between light and temperature would provide the bacteria clues of
environmental location and dictate/modulate light photosensing in A. baumannii.
PMID- 28500706
TI - Common Structural Elements in the Chromophore Binding Pocket of the Pfr State of
Bathy Phytochromes.
AB - Phytochromes are bimodal photoreceptors which, upon light absorption by the
tetrapyrrole chromophore, can be converted between a red-absorbing state (Pr) and
far-red-absorbing state (Pfr). In bacterial phytochromes, either Pr or Pfr are
the thermally stable states, thereby constituting the classes of prototypical and
bathy phytochromes, respectively. In this work, we have employed vibrational
spectroscopies to elucidate the origin of the thermal stability of the Pfr states
in bathy phytochromes. Here, we present the first detailed spectroscopic analysis
of RpBphP6 (Rhodopseudomas palustris), which together with results obtained for
Agp2 (Agrobacterium tumefaciens) and PaBphP (Pseudomonas aeruginosa) allows
identifying common structural properties of the Pfr state of bathy phytochromes,
which are (1) a homogenous chromophore structure, (2) the protonated ring C
propionic side chain of the chromophore and (3) a retarded H/D exchange at the
ring D nitrogen. These properties are related to the unique strength of the
hydrogen bonding interactions between the ring D N-H group with the side chain of
the conserved Asp194 (PaBphP numbering). As revealed by a comparative analysis of
homology models and available crystal structures of Pfr states, these
interactions are strengthened by an Arg residue (Arg453) only in bathy but not in
prototypical phytochromes.
PMID- 28500707
TI - Introduction, Festschrift in honor of Wolfgang Gartner.
PMID- 28500708
TI - Proteorhodopsin Photocycle Kinetics Between pH 5 and pH 9.
AB - The retinal protein proteorhodopsin is a homolog of the well-characterized light
driven proton pump bacteriorhodopsin. Basic mechanisms of proton transport seem
to be conserved, but there are noticeable differences in the pH ranges of proton
transport. Proton transport and protonation state of a carboxylic acid side
chain, the primary proton acceptor, are correlated. In case of proteorhodopsin,
the pKa of the primary proton acceptor Asp-97 (pKa ~ 7.5) is unexpectedly close
to environmental pH (pH ~ 8). A significant fraction of proteorhodopsin is
possibly inactive at natural pH, in contrast to bacteriorhodopsin. We
investigated photoinduced kinetics of proteorhodopsin between pH 5 and pH 9 by
time resolved UV/vis absorption spectroscopy. Kinetics is inhomogeneous within
that pH region and can be considered as a superposition of two fractions. These
fractions are correlated with the Asp-97 titration curve. Beside Asp-97,
protonation equilibria of other groups influence kinetics, but the observations
do not point toward major differences of primary proton acceptor function in
proteorhodopsin and bacteriorhodopsin. The pKa of proteorhodopsin and some of its
variants is suspected to be an example of molecular adaptation to the physiology
of the original organisms.
PMID- 28500709
TI - The Expanded Red/Green Cyanobacteriochrome Lineage: An Evolutionary Hot Spot.
AB - This article highlights the paper by Rockwell et al. in the current issue of
Photochemistry and Photobiology. Rockwell et al. describe the discovery of novel
two-Cys photocycles within the "expanded red/green" (XRG) cyanobacteriochrome
(CBCR) lineage. Comprehensive phylogenetic analysis revealed that several XRG
CBCRs possess a second Cys residue in the DXCF (Asp-Xaa-Cys-Phe) motif conserved
among the DXCF CBCR lineage. Spectral studies identified that these CBCRs showed
green/blue or ultraviolet/blue reversible photoconversion abilities. The
green/blue reversible photocycle had not been reported previously among the XRG
CBCR lineage. Based on these findings, Rockwell et al. replaced three amino acid
residues in a red/green reversible CBCR, NpR6012g4, and succeeded in constructing
a violet/green reversible photocycle. These findings, together with previous
studies, provide a good explanation for the evolutionary flexibility of the XRG
CBCRs.
PMID- 28500710
TI - Characterization of the Blue-Light-Activated Adenylyl Cyclase mPAC by Flash
Photolysis and FTIR Spectroscopy.
AB - The recently discovered photo-activated adenylyl cyclase (mPAC from Microcoleus
chthonoplastes) is the first PAC that owes a light-, oxygen- and voltage
sensitive (LOV) domain for blue-light sensing. The photoreaction of the mPAC
receptor was studied by time-resolved UV/vis and light-induced Fourier transform
infrared (FTIR) absorption difference spectroscopy. The photocycle comprises of
the typical triplet state LOV715 and the thio-adduct state LOV390 . While the
adduct state decays with a time constant of 8 s, the lifetime of the triplet
state is with 656 ns significantly shorter than in all other reported LOV
domains. The light-induced FTIR difference spectrum shows the typical bands of
the LOV390 and LOV450 intermediates. The negative S-H stretching vibration at
2573 cm-1 is asymmetric suggesting two rotamer configurations of the protonated
side chain of C194. A positive band at 3632 cm-1 is observed, which is assigned
to an internal water molecule. In contrast to other LOV domains, mPAC exhibits a
second positive feature at 3674 cm-1 which is due to the O-H stretch of a second
intrinsic water molecule and the side chain of Y476. We conclude that the latter
might be involved in the dimerization of the cyclase domain which is crucial for
ATP binding.
PMID- 28500711
TI - Quantum Chemical Spin Densities for Radical Cations of Photosynthetic Pigment
Models.
AB - The spin densities of radical cations of magnesium porphyrin, magnesium chlorine
and a truncated chlorophyll a model are calculated with density-functional theory
and multiconfigurational quantum chemical methods. The latter serve as a
reference for approximate density-functional theory which yields spin densities
that may suffer from the self-interaction error. We carried out complete active
space self-consistent field calculations with increasing active orbital spaces to
systematically converge qualitatively correct spin densities. In particular, for
the magnesium chlorine and chlorophyll a model radical cations, this is not easy
to achieve because of the lower symmetry compared to magnesium porphyrin.
Strategies had to be employed which allowed us to consider very large active
orbital spaces. We explored restricted active space self-consistent field and
density-matrix renormalization group calculations. Based on these reference data,
we assessed the accuracy of different density-functional approximations. We show
that in particular, exchange-correlation model potentials with correct asymptotic
behavior yield good spin densities, and we find, in agreement with previous
studies on different classes of compounds, that hybrid functionals systematically
increase spin-polarization effects with increasing amounts of exact exchange. Our
results provide a starting point for investigations of spin densities of more
complex systems such as the hinge model for the primary electron donor in
photosystem II.
PMID- 28500712
TI - Time-Resolved Energetics of Photoprocesses in Prokaryotic Phytochrome-Related
Photoreceptors.
AB - Time-resolved photoacoustics (PA) is uniquely able to explore the energy
landscape of photoactive proteins and concomitantly detects light-induced
volumetric changes (DeltaV) accompanying the formation and decay of transient
species in a time window between ca. 20 ns and 5 MUs. Here, we report PA
measurements on diverse photochromic bilin-binding photoreceptors of prokaryotic
origin: (1) the chromophore-binding GAF3 domain of the red (R)/green (G)
switching cyanobacteriochrome 1393 (Slr1393g3) from Synechocystis; (2) the
red/far red (R/FR) Synechocystis Cph1 phytochrome; (3) full-length and truncated
constructs of Xanthomonas campestris bacteriophytochrome (XccBphP), absorbing up
to the NIR spectral region. In almost all cases, photoisomerization results in a
large fraction of energy dissipated as heat (up to 90%) on the sub-ns scale,
reflecting the low photoisomerization quantum yield (<0.2). This "prompt" step is
accompanied by a positive DeltaV1 = 5-12.5 mL mol-1 . Formation of the first
intermediate is the sole process accessible to PA, with the notable exception of
Slr1393g3-G for which DeltaV1 = +4.5 mL mol-1 is followed by a time-resolved,
energy-conserving contraction DeltaV2 = -11.4 mL mol-1 , tau2 = 180 ns at 2.4
degrees C. This peculiarity is possibly due to a larger solvent occupancy of the
chromophore cavity for Slr1393g3-G.
PMID- 28500713
TI - Photochemical Properties of the Red-shifted Channelrhodopsin Chrimson.
AB - Color-tuned variants of channelrhodopsins allow for selective optogenetic
manipulation of different host cell populations. Chrimson is the channelrhodopsin
with the longest wavelength absorbance maximum. We characterize its photochemical
properties at different pH values corresponding to two protonation states of the
counterion for the protonated Schiff base. Both states will lead to a functional
channel opening, but the route is different as reflected in the photochemical
states observed spectroscopically. The light-induced isomerization kinetics
change with the local electrostatic environment, becoming faster with the
presence of an anionic counterion. The spectral effect is stronger on the ground
state energy surface. From the excited state, a bifurcated pathway leads to the
electronic ground state resulting in a pronounced excitation wavelength
dependence. The subsequent steps in the photocycles at pH 6 and pH 9.5 differ in
the accumulation of states with a protonated and deprotonated Schiff base,
respectively, that can be correlated with the open channel. Therefore, different
protonation states are preserved in the open and the initial states. Chrimson's
photocycle at alkaline pH shows features observed in other rhodopsins without an
internal proton donor to the Schiff base, but it accumulates an intermediate with
an even longer lifetime reflecting slow recovery of the initial state.
PMID- 28500714
TI - Sensory Rhodopsin I and Sensory Rhodopsin II Form Trimers of Dimers in Complex
with their Cognate Transducers.
AB - Archaeal photoreceptors consist of sensory rhodopsins in complex with their
cognate transducers. After light excitation, a two-component signaling chain is
activated, which is homologous to the chemotactic signaling cascades in
enterobacteria. The latter system has been studied in detail. From structural and
functional studies, a picture emerges which includes stable signaling complexes,
which assemble to receptor arrays displaying hexagonal structural elements. At
this higher order structural level, signal amplification and sensory adaptation
occur. Here, we describe electron microscopy data, which show that also the
archaeal phototaxis receptors sensory rhodopsin I and II in complex with their
cognate transducers can form hexagonal lattices even in the presence of a
detergent. This result could be confirmed by molecular dynamics calculations,
which revealed similar structural elements. Calculations of the global modes of
motion displayed one mode, which resembles the "U"-"V" transition of the
NpSRII:NpHtrII complex, which was previously argued to represent a functionally
relevant global conformational change accompanying the activation process
[Ishchenko et al. (2013) J. Photochem. Photobiol. B 123, 55-58]. A model of
cooperativity at the transmembrane level is discussed.
PMID- 28500715
TI - Crystal Effects on Mesobilirubin: A Combined NMR Spectroscopic and Density
Functional Theory Study.
AB - We report solid-state NMR investigations of crystal effects in powdered
mesobilirubin-IXalpha, an open-chain tetrapyrrole that is structurally related to
bilirubin-IXalpha but hydrogenated at the 3- and 18-vinyl groups. 13 C and 15 N
cross-polarization magic-angle spinning (CP/MAS) NMR experiments were performed
on the compound at natural abundance. To facilitate the spectral analysis,
density functional calculations were carried out at the B3LYP/6-311G(d,p) level
of theory, using an enneameric cluster to simulate the solid. The 1 H, 13 C and
15 N chemical shift data calculated for the enneamer are in a good agreement with
those observed in the experimental spectra, and the relative order of the
calculated resonances was thus used to confirm the tentative assignments obtained
mainly from the heteronuclear correlation spectra. The observed signal splittings
of a small subset of the 13 C resonances in the peripheral regions of the two
terminal rings provide evidence for microcrystalline heterogeneity of the
powdered compound.
PMID- 28500716
TI - Functional Expression of Gloeobacter Rhodopsin in Synechocystis sp. PCC6803.
AB - Proteorhodopsins are light-driven proton pumps that occur widespread in Nature,
where they function predominantly in environments with high incident irradiance.
Their maximal absorbance is usually in the blue range, but can be extended into
the (far)red range of the electromagnetic spectrum. Because they can be expressed
heterologously, they may be exploited in studies aimed at increasing the
efficiency of photosynthesis. Here we report further studies toward this goal, by
comparing the expression of two different bacterial rhodopsins (Proteorhodopsin
and Gloeobacter rhodopsin) in the model cyanobacterium Synechocystis sp. PCC6803.
In particular, we investigated the pigments bound by the respective apo-opsins,
and the oligomeric state of the corresponding holo-rhodopsins, both in
Escherichia coli and in the cyanobacterial membranes. We conclude that the two
proton-pumping rhodopsins are predominantly present in an oligomeric state
(hexamers for Proteorhodopsin and trimers for Gloeobacter rhodopsin).
Furthermore, Gloeobacter rhodopsin is able to bind an antenna carotenoid (in
addition to retinal) and has the highest pumping rate at given light intensity.
However, its lower expression level will decrease its physiological
effectiveness. It remains to be established which of these two bacterial
rhodopsins is best in stimulating the growth rate of its cyanobacterial host.
PMID- 28500717
TI - Epigenetically Enhanced Photodynamic Therapy (ePDT) is Superior to Conventional
Photodynamic Therapy for Inducing Apoptosis in Cutaneous T-Cell Lymphoma.
PMID- 28500718
TI - RPE65 and the Accumulation of Retinyl Esters in Mouse Retinal Pigment Epithelium.
AB - The RPE65 protein of the retinal pigment epithelium (RPE) enables the conversion
of retinyl esters to the visual pigment chromophore 11-cis retinal. Fresh 11-cis
retinal is generated from retinyl esters following photoisomerization of the
visual pigment chromophore to all-trans during light detection. Large amounts of
esters accumulate in Rpe65-/- mice, indicating their continuous formation when 11
cis retinal generation is blocked. We hypothesized that absence of light, by
limiting the conversion of esters to 11-cis retinal, would also result in the
build-up of retinyl esters in the RPE of wild-type mice. We used HPLC to quantify
ester levels in organic extracts of the RPE from wild-type and Rpe65-/- mice.
Retinyl ester levels in Sv/129 wild-type mice that were dark adapted for various
intervals over a 4-week period were similar to those in mice raised in cyclic
light. In C57BL/6 mice however, which contain less Rpe65 protein, dark adaptation
was accompanied by an increase in ester levels compared to cyclic light controls.
Retinyl ester levels were much higher in Rpe65-/- mice compared to wild type and
kept increasing with age. The results suggest that the RPE65 role in retinyl
ester homeostasis extends beyond enabling the formation of 11-cis retinal.
PMID- 28500719
TI - Novel Thermostable Flavin-binding Fluorescent Proteins from Thermophilic
Organisms.
AB - Flavin-binding fluorescent proteins (FbFPs) are small, oxygen-independent in vivo
reporters, derived from Light Oxygen Voltage (LOV) domains of photoreceptors.
Here, we investigated the thermostability of existing, as well as novel FbFPs,
whose genes were identified in genome sequences of various thermophilic bacteria
as well as metagenomic libraries from hot springs in the Yellowstone National
Park. Detailed in vitro analyses revealed that two of those fluorescent reporter
proteins were highly thermostable, exhibiting melting temperatures above 75
degrees C.
PMID- 28500720
TI - Casting Away the Shadows: Elucidating the Role of Light-mediated
Posttranscriptional Control in Plants.
AB - Light signals trigger precise changes in gene expression networks that activate
distinctive developmental programs in plants. The transcriptome is shaped at
different stages, both by the regulation of gene expression and also by
posttranscriptional mechanisms that alter the sequence or abundance of the
transcripts generated. Posttranscriptional mechanisms have attracted much
interest in recent years with the advent of high-throughput technologies and
bioinformatics tools. One such posttranscriptional process, alternative splicing,
increases proteome diversity without increasing gene number by changing the
function of individual proteins, while another, miRNA-mediated gene silencing,
fine-tunes the amount of mRNA produced. The manner in which plants make use of
these two crucial posttranscriptional mechanisms to respond to light and adapt to
their environment is the focus of active research. In this review, we summarize
the current knowledge of light-mediated posttranscriptional control in
Arabidopsis thaliana and focus on the biological impact of the various
posttranscriptional processes. We also discuss a potential cross talk between the
alternative splicing and miRNA pathways, highlighting the complexity of light
responsiveness.
PMID- 28500721
TI - Structural and Vibrational Characterization of the Chromophore Binding Site of
Bacterial Phytochrome Agp1.
AB - Agp1 is a prototypical bacterial phytochrome from Agrobacterium fabrum harboring
a biliverdin cofactor which reversibly photoconverts between a red-light
absorbing (Pr) and a far-red-light-absorbing (Pfr) states. The reaction mechanism
involves the isomerization of the bilin-chromophore followed by large structural
changes of the protein matrix that are coupled to protonation dynamics at the
chromophore binding site. Histidines His250 and His280 participate in this
process. Although the three-dimensional structure of Agp1 has been solved at high
resolution, the precise position of hydrogen atoms and protonation pattern in the
chromophore binding pocket has not been investigated yet. Here, we present
protonated structure models of Agp1 in the Pr state involving appropriately
placed hydrogen atoms that were generated by hybrid quantum mechanics/molecular
mechanics- and electrostatic calculations and validated against experimental
structural- and spectroscopic data. Although the effect of histidine protonation
on the vibrational spectra is weak, our results favor charge neutral H250 and
H280 both protonated at Nepsilon. However, a neutral H250 with a proton at
Nepsilon and a cationic H280 may also be possible. Furthermore, the present QM/MM
calculations of IR and Raman spectra of Agp1 containing isotope-labeled BV
provide a detailed vibrational assignment of the biliverdin modes in the
fingerprint region.
PMID- 28500722
TI - UV-Resistant Actinobacteria from High-Altitude Andean Lakes: Isolation,
Characterization and Antagonistic Activities.
AB - Polyextremophiles are present in a wide variety of extreme environments in which
they must overcome various hostile conditions simultaneously such as high UVB
radiation, extreme pHs and temperatures, elevated salt and heavy-metal
concentration, low-oxygen pressure and scarce nutrients. High-altitude Andean
lakes (HAALs; between 2000 and 4000 m) are one example of these kinds of
ecosystems suffering from the highest total solar and UVB radiation on Earth
where an abundant and diverse polyextremophilic microbiota was reported. In this
work, we performed the first extensive isolation of UV-resistant actinobacteria
from soils, water, sediments and modern stromatolites at HAALs. Based on the 16S
rRNA sequence, the strains were identified as members of the genera Streptomyces,
Micrococcus, Nesterenkonia, Rhodococcus, Microbacterium, Kocuria, Arthrobacter,
Micromonospora, Blastococcus, Citrococcus and Brevibacterium. Most isolates
displayed resistance to multiple environmental stress factors confirming their
polyextremophilic nature and were able to produce effective antimicrobial
compounds. HAALs constitute a largely unexplored repository of UV-resistant
actinobacteria, with high potential for the biodiscovery of novel natural
products.
PMID- 28500723
TI - Self-limited membranous glomerulonephritis due to syphilis.
PMID- 28500725
TI - Study Break: Misconduct in Research and Publication: a Dilemma That Is Taking
Place
PMID- 28500724
TI - Grape seed proanthocyanidin extract ameliorates inflammation and adiposity by
modulating gut microbiota in high-fat diet mice.
AB - SCOPE: Obesity and associated metabolic complications is a worldwide public
health issue. Gut microbiota have been recently linked to obesity and its related
inflammation. In this study, we have explored the anti-inflammatory effect of
grape seed proanthocyanindin extract (GSPE) in the high-fat diet (HFD)-induced
obesity and identified the contribution of the gut microbiota to GSPE effects on
metabolism. METHODS AND RESULTS: Mice were fed a normal diet and a high-fat diet
with or without GSPE (300 mg/kg body weight/day) by oral gavage for 7 weeks.
Supplementation with GSPE significantly decreased plasma levels of inflammatory
factors such as TNF-alpha, IL-6 and MCP-1, companied with ameliorated macrophage
infiltration in epidydimal fat and liver tissues. Furthermore, GSPE also reduced
epidydimal fat mass and improved insulin sensitivity. 16S rDNA analyses revealed
that GSPE supplementation modulated the gut microbiota composition and certain
bacteria including Clostridium XIVa, Roseburia and Prevotella. More importantly,
depleting gut microbiota by antibiotics treatment abolished the beneficial
effects of GSPE on inflammation and adiposity. CONCLUSION: Our study identifies
the novel links between gut microbiota alterations and metabolic benefits by GSPE
supplementation, providing possibilities for the prevention and treatment of
metabolic disorders by targeting gut microbiota through a potential prebiotic
agent GSPE.
PMID- 28500726
TI - Mutations associated with drug resistance and prevalence of vaccine escape
mutations in patients with chronic hepatitis B infection.
AB - The Brazilian public health system (SUS) has provided antiviral drugs for chronic
hepatitis B treatment for over 10 years, but a system for monitoring for drug
related resistance mutations is not available. Determine the presence of HBV
mutations associated with resistance to nucleos(t)ide analogs among 81 patients
with chronic HBV infection in Salvador-BA-Brazil. HBV-DNA was PCR amplified with
primers deduced from the rt domain at the HBV P gene, the sequence extended 1032
bp (from amino acid 1 to 344-rt domain). Those sequences were submitted to the
HBV drug resistance database to retrieve each mutation according to the genotype.
HBV genotype A1 (85.2%) was the most prevalent, followed by genotype A2 (4.9%), F
(6.2%), and C1, D2, and D4 (1.2% each). Six patients (7%) exhibited resistance
mutations to LAM, ETV, and TDF: two with patterns L180M + M204V and four with
other different patterns: L80I + L180M + M204I; L80V + L180M + M204V; M204I;
A194T. All of these mutations were present in patients with genotype A (four A1
and two A2). In addition, four mutations in gene S (three cases with the sI195M
mutation and one with the W196L mutation), were detected, corresponding to a rate
of 6% of vaccine escape mutations. Althougth the small sample size, an
association was found between the occurrence of HBV resistance mutations and
HBeAg positivity, co-infection with HIV and a history of treatment for HBV and/or
HIV.
PMID- 28500728
TI - Immunolocalization of Substance P and NK-1 Receptor in ADIPOSE Stem Cells.
AB - Substance P (SP) is a neuropeptide belonging to the thachykinin peptide family.
SP, after binding to its receptor, the neurokinin 1 receptor (NK1R), controls
several transcription factors such as NF-kappaB, hypoxia inducible factor (HIF
1alpha), c-myc, c-fos, c-jun, and AP-1. SP and NK1R have a widespread
distribution in both the central and peripheral nervous systems. They are also
present in cells not belonging to the nervous system (immune cells, placenta,
etc.). SP is located in all body fluids, that is, blood, cerebrospinal fluid,
etc., making it ubiquitous throughout the human body. SP and NK1R genes are
expressed in the stem cell line TF-1 and in primary stem cells derived from human
placental cord blood. However, to our knowledge, the presence of SP and the NK1R
receptor in adipose stem cells (ADSC) is unknown. We demonstrated by
immunofluorescence the localization of SP and NK1R in human and rat ADSC. SP and
NK1R are located in both the cytoplasm and the nucleus of these cells. The NK1R
is higher in the nucleus than in the cytoplasm of ADSCs. By Western blot we
demonstrated the presence of different isoforms of NK1R that have different
subcellular locations in the ADSC. SP induces proliferation and mitogenesis
through NK1R in ADSCs. These findings reported here for the first time suggest an
important role for a SP/NK1R system, either as genetic and/or epigenetic factor,
in both the cytoplasm and nucleus functions of the ADSCs. J. Cell. Biochem. 118:
4686-4696, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28500729
TI - Electrophilic Activation of Iodonium Ylides by Halogen-Bond-Donor Catalysis for
Cross-Enolate Coupling.
AB - The umpolung alkylation of silyl enol ethers with an iodonium(III) ylide proceeds
under mild conditions to afford various 1,4-dicarbonyl compounds in high yields
in the presence of a halogen-bonding catalyst. Unlike typical transition-metal
activation processes of such ylide precursors, which tend to proceed via
carbenoid intermediates, experimental and computational studies indicate that
halogen bonding (XB) between the XB donor catalyst and the iodonium ylide plays a
crucial role in promoting the reaction. The identification of a compatible
Bronsted base catalyst enabled the extension of this method to enols generated in
situ to give the corresponding adducts in good yields.
PMID- 28500727
TI - Biological function and histone recognition of family IV bromodomain-containing
proteins.
AB - Bromodomain proteins function as epigenetic readers that recognize acetylated
histone tails to facilitate the transcription of target genes. There are
approximately 60 known human bromodomains, which are divided into eight sub
families based on structural conservation. The bromodomain-containing proteins in
family IV include seven members (BRPF1, BRPF2, BRPF3, BRD7, BRD9, ATAD2, and
ATAD2b). The bromodomains of each of these proteins recognize and bind
acetyllysine residues on histone tails protruding from the nucleosome. However,
the histone marks recognized by each bromodomain protein can be very different.
The BRPF1 subunit of the MOZ histone acetyltransferase (HAT) recognizes
acetylated histones H2AK5ac, H4K12ac, H3K14ac, H4K8ac, and H4K5ac. While the
bromodomain of BRD7, a member of the SWI/SNF complex, was shown to preferentially
recognize acetylated histones H3K9ac, H3K14ac, H4K8ac, H4K12ac, and H4K16ac. The
bromodomains of BRPF2 and BRPF3 have similar sequences, and function as part of
the HBO1 HAT complex, but there is limited data on which histone ligands they
bind. Similarly, there is little known about the histone targets of the BRD9 and
ATAD2b bromodomain proteins. Interestingly, the ATAD2 bromodomain was recently
shown to preferentially bind to the di-acetylated H4K5acK12ac mark found in newly
synthesized histones following DNA replication. However, despite the
physiological importance of the family IV bromodomains, little is known about how
they function at the molecular or atomic level. In this review, we summarize our
understanding of how family IV bromodomains recognize and select for acetyllysine
marks and discuss the importance of acetylated histone recognition for their
biological functions.
PMID- 28500730
TI - Comparative prognostic value of postprocedural creatine kinase myocardial band
and high-sensitivity troponin T in patients with non-ST-segment elevation
myocardial infarction undergoing percutaneous coronary intervention.
AB - OBJECTIVES: We aimed to assess the prognostic value of postprocedural creatine
kinase myocardial band (CK-MB) and cardiac troponin (cTn) in patients with non-ST
segment elevation myocardial infarction (NSTEMI). BACKGROUND: Whether
postprocedural CK-MB or cTn is a better biomarker to stratify the risk after
percutaneous coronary intervention (PCI) remains unknown. METHODS: This study
included 2,077 patients with NSTEMI undergoing early PCI. Peak postprocedural
values of CK-MB and high-sensitivity cTn T (hs-cTnT) were analyzed. The primary
outcome was 3-year mortality. RESULTS: The median values of peak postprocedural
CK-MB and hs-cTnT were 18.3 U L-1 and 0.140 ug L-1 , respectively. Overall, 211
patients died during follow-up. There were 129 deaths in patients with CK-MB >the
median value and 82 deaths in those with CK-MB <=the median value (Kaplan-Meier
estimates of 3-year mortality, 18.9% and 14.0%, respectively; hazard ratio [HR] =
1.52, 95% confidence interval [CI] 1.16-2.01; P < 0.001). There were 134 deaths
in patients with hs-cTnT >the median value and 77 deaths in patients with hs-cTnT
<=the median value (Kaplan-Meier estimates of 3-year mortality, 19.9% and 13.2%,
respectively; HR = 1.90 [1.44-2.52]; P < 0.001). After adjustment, peak
postprocedural CK-MB (adjusted HR = 1.05 [1.02-1.07], P < 0.001 for each 24 U L-1
increment) and hs-cTnT (adjusted HR = 1.12 [1.01-1.25], P = 0.037 for each unit
higher log hs-cTnT) remained independently associated with the risk of 3-year
mortality. The C-statistic(s) of the model with CK-MB and hs-cTnT were 0.789
[0.757-0.817] and 0.793 [0.762-0.821], respectively (P = 0.585). CONCLUSION: In
patients with NSTEMI undergoing early PCI, peak postprocedural CK-MB and hs-cTnT
are independently associated with the risk of 3-year mortality. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28500731
TI - Alternative plasticizer, 4-cyclohexene-1,2-dicarboxylic acid dinonyl ester, for
blood containers with protective effects on red blood cells and improved cold
resistance.
AB - Di (2-ethylhexyl) phthalate (DEHP), a typical plasticizer used for polyvinyl
chloride (PVC), is eluted from PVC-made blood containers and protects against red
blood cell (RBC) hemolysis. However, concerns have arisen regarding the
reproductive and developmental risks of DEHP in humans, and the use of
alternative plasticizers for medical devices has been recommended worldwide. In
this study, we propose that the use of a novel plasticizer, 4-cyclohexene-1,2
dicarboxylic acid dinonyl ester (DL9TH), could help produce more useful and safe
blood containers. PVC sheet containing DL9TH and di (2-ethylhexyl) 4-cyclohexene
1,2-dicarboxylate (DOTH) provides comparable or superior protective effects to
RBCs relative to PVC sheet containing DEHP or di-isononyl-cyclohexane-1,2
dicarboxylate (DINCH(r) , an alternative plasticizer that has been used in PVC
sheets for blood containers). The total amount of plasticizer eluted from
DOTH/DL9TH-PVC sheets is nearly the same as that eluted from DEHP-PVC sheets. In
addition, DOTH/DL9TH-PVC has better cold resistance than DEHP- and DINCH(r) -PVC
sheets. In vitro and in vivo tests for biological safety based on International
Organization for Standardization guidelines (10993 series) suggest that the
DOTH/DL9TH-PVC sheet can be used safely. Subchronic toxicity testing of DL9TH in
male rats in accordance with the principles of Organisation for Economic Co
operation and Development Test Guideline 408 showed that DL9TH did not induce
adverse effects up to the highest dose level tested (717 mg/kg body weight/day).
There were no effects on testicular histopathology and sperm counts, and no
indications of endocrine effects: testosterone, thyroid-stimulating hormone,
follicle-stimulating hormone, and 17beta-estradiol were unchanged by the
treatment, compared with the control group. (c) 2017 Wiley Periodicals, Inc. J
Biomed Mater Res Part B: Appl Biomater, 106B: 1052-1063, 2018.
PMID- 28500732
TI - Costs of cancer care in children and adolescents in Ontario, Canada.
AB - BACKGROUND: Cancer in children and adolescents presents unique issues regarding
treatment and survivorship, but few studies have measured economic burden. We
estimated health care costs by phase of cancer care, from the public payer
perspective, in population-based cohorts. METHODS: Children newly diagnosed at
ages 0 days-14.9 years and adolescents newly diagnosed at 15-19.9 years, from
January 1, 1995 to June 30, 2010, were identified from Ontario cancer registries,
and each matched to three noncancer controls. Data were linked with
administrative records describing resource use for cancer and other health care.
Total and net (patients minus controls) resource-specific costs ($CAD2012) were
estimated using generalized estimating equations for four phases of care:
prediagnosis (60 days), initial (360 days), continuing (variable), final (360
days). RESULTS: Mean ages at diagnosis were 6 years for children (N = 4,606) and
17 years for adolescents (N = 2,443). Mean net prediagnosis phase 60-day costs
were $6,177 for children and $1,018 for adolescents. Costs for initial,
continuing, and final phases were $138,161, $15,756, and $316,303 per 360 days
for children, and $62,919, $7,071, and $242,008 for adolescents. The highest
initial phase costs were for leukemia patients ($156,225 per 360 days for
children and $171,275 for adolescents). The final phase was the most costly
($316,303 per 360 days for children and $242,008 for adolescents). CONCLUSIONS:
Costs for children with cancer are much higher than for adolescents and much
higher than those reported in adults. Comprehensive population-based long-term
estimates of cancer costs are useful for health services planning and cost
effectiveness analysis.
PMID- 28500733
TI - Bordetella effector BopN is translocated into host cells via its N-terminal
residues.
AB - Bordetella bronchiseptica infects a wide variety of mammals, the type III
secretion system (T3SS) being involved in long-term colonization by Bordetella of
the trachea and lung. T3SS translocates virulence factors (commonly referred to
as effectors) into host cells, leading to alterations in the host's physiological
function. The Bordetella effectors BopN and BteA are known to have roles in up
regulation of IL-10 and cytotoxicity, respectively. Nevertheless, the mechanism
by which BopN is translocated into host cells has not been examined in sufficient
detail. Therefore, to determine the precise mechanisms of translocation of BopN
into host cells, truncated derivatives of BopN were built and the derivatives'
ability to translocate into host cells evaluated by adenylate cyclase-mediated
translocation assay. It was found that N-terminal amino acid (aa) residues 1-200
of BopN are sufficient for its translocation into host cells. Interestingly, BopN
translocation was completely blocked by deletion of the N-terminal aa residues 6
50, indicating that the N-terminal region is critical for BopN translocation.
Furthermore, BopN appears to play an auxiliary role in BteA-mediated
cytotoxicity. Thus, BopN can apparently translocate into host cells and may
facilitate activity of BteA.
PMID- 28500734
TI - Differentiation of human olfactory bulb-derived neural stem cells toward
oligodendrocyte.
AB - In the central nervous system (CNS), oligodendrocytes are the glial element in
charge of myelin formation. Obtaining an overall presence of oligodendrocyte
precursor cells/oligodendrocytes (OPCs/OLs) in culture from different sources of
NSCs is an important research area, because OPCs/OLs may provide a promising
therapeutic strategy for diseases affecting myelination of axons. The present
study was designed to differentiate human olfactory bulb NSCs (OBNSCs) into
OPCs/OLs and using expression profiling (RT-qPCR) gene, immunocytochemistry, and
specific protein expression to highlight molecular mechanism(s) underlying
differentiation of human OBNSCs into OPCs/OLs. The differentiation of OBNSCs was
characterized by a simultaneous appearance of neurons and glial cells. The
differentiation medium, containing cAMP, PDGFA, T3, and all-trans-retinoic acid
(ATRA), promotes OBNSCs to generate mostly oligodendrocytes (OLs) displaying
morphological changes, and appearance of long cytoplasmic processes. OBNSCs
showed, after 5 days in OLs differentiation medium, a considerable decrease in
the number of nestin positive cells, which was associated with a concomitant
increase of NG2 immunoreactive cells and few O4(+)-OPCs. In addition, a
significant up regulation in gene and protein expression profile of stage
specific cell markers for OPCs/OLs (CNPase, Galc, NG2, MOG, OLIG1, OLIG2, MBP),
neurons, and astrocytes (MAP2, beta-TubulinIII, GFAP) and concomitant decrease of
OBNSCs pluripotency markers (Oct4, Sox2, Nestin), was demonstrated following
induction of OBNSCs differentiation. Taken together, the present study
demonstrate the marked ability of a cocktail of factors containing PDGFA, T3,
cAMP, and ATRA, to induce OBNSCs differentiation into OPCs/OLs and shed light on
the key genes and pathological pathways involved in this process.
PMID- 28500735
TI - Increased expression of CD38 and HLADR in HIV-infected patients with oral lesion.
AB - Persistent immune actiation is associated with innadequate immune recovery in HIV
patients. This study assessed the relationship between frequency of expression of
cell activation markers (CD38 and HLADR) and presence of oral lesions in HIV-1
infected patients. Fifty-seven HIV-infected persons, undergoing antiretroviral
treatment, were divided into three groups, according to the number of CD4+ T
cells and CD4+ /CD8+ ratio: adequate, partial, and inadequate immune
restauration. All patients underwent full mouth assessments for saliva flow
measurement, oral mucosal lesion, periodontal disease, and severity of
periodontitis. Immune activation markers levels were compared according to three
groups of periodontal disease ("No periodontal disease," "gingivitis," and
"periodontitis"). Oral mucosal lesions (P = 0.03) and peridodontal disease (P =
0.03) were associated with lower CD4+ /CD8+ ratio. Patients with oral mucosal
lesions had significantly higher median levels of HLADR and CD38 markers in all T
lymphocytes populations than patients without oral lesions. Patients with
gingivitis and with periodontitis presented significantly higher median levels of
CD3+ HLADR+ , CD4+ HLADR+ , CD8+ HLADR+ , and CD3+ CD38+ and significantly lower
CD4+ /CD8+ ratio than patients with no periodontal disease. Increased levels of
HLADR and CD38 expressions in peripheral blood were associated with oral lesions
in HIV-positive patients. Periodontal disease was associated with HLADR
expression.
PMID- 28500736
TI - High density lipoprotein (HDL) reverses palmitic acid induced energy metabolism
imbalance by switching CD36 and GLUT4 signaling pathways in cardiomyocyte.
AB - In our previous study palmitic acid (PA) induced lipotoxicity and switches energy
metabolism from CD36 to GLUT4 in H9c2 cells. Low level of high density
lipoprotein (HDL) is an independent risk factor for cardiac hypertrophy.
Therefore, we in the present study investigated whether HDL can reverse PA
induced lipotoxicity in H9c2 cardiomyoblast cells. In this study, we treated H9c2
cells with PA to create a hyperlipidemia model in vitro and analyzed for CD36 and
GLUT4 metabolic pathway proteins. CD36 metabolic pathway proteins (phospho-AMPK,
SIRT1, PGC1alpha, PPARalpha, CPT1beta, and CD36) were decreased by high PA (150
and 200 MUg/MUl) concentration. Interestingly, expression of GLUT4 metabolic
pathway proteins (p-PI3K and pAKT) were increased at low concentration (50
MUg/MUl) and decreased at high PA concentration. Whereas, phospho-PKCzeta, GLUT4
and PDH proteins expression was increased in a dose dependent manner. PA treated
H9c2 cells were treated with HDL and analyzed for cell viability. Results showed
that HDL treatment induced cell proliferation efficiency in PA treated cells. In
addition, HDL reversed the metabolic effects of PA: CD36 translocation was
increased and reduced GLUT4 translocation, but HDL treatment significantly
increased CD36 metabolic pathway proteins and reduced GLUT4 pathway proteins. Rat
neonatal cardiomyocytes showed similar results. In conclusion, HDL reversed
palmatic acid-induced lipotoxicity and energy metabolism imbalance in H9c2
cardiomyoblast cells and in neonatal rat cardiomyocyte cells.
PMID- 28500738
TI - Occurrence and predictors of acute stent recoil-A comparison between the xience
prime cobalt chromium stent and the promus premier platinum chromium stent.
AB - OBJECTIVES: To compare the occurrence of acute stent recoil in two different
stent types (platinum chromium and cobalt chromium) and identify the potential
predictors of significant acute stent recoil. BACKGROUND: Acute stent recoil is
frequently observed after percutaneous coronary intervention and has been
associated with in-stent restenosis and in-stent thrombosis. Different stent
designs may result in varying degrees of stent recoil. METHODS: From a registry
of "all-comers" treated with either the Xience Prime Cobalt Chromium or Promus
Premier Platinum Chromium stent, a random sample of 100 patients was drawn. Acute
stent recoil was defined as the minimal luminal diameter (MLD) of the last
inflated balloon minus the MLD after, divided by the MLD of the last inflated
balloon. Significant acute stent recoil was defined as recoil >=10%. RESULTS: A
total of 123 lesions (61 Xience Prime vs 62 Promus Premier) in 100 patients were
analyzed. Acute stent recoil of 8.6 +/- 4.9% was observed in the Xience Prime
group versus 8.7 +/- 4.2% in the Promus Premier group, P = 0.970. In a
multivariate model for significant acute stent recoil, a stent/vessel ratio >=1
(hazard ratio 4.64 [1.94-11.12], P = 0.001), a balloon/stent ratio >1 (hazard
ratio 3.83 [1.12-13.14], P = 0.032) and direct stenting (hazard ratio 0.42 [0.18
0.96], P = 0.039) were identified as predictors. CONCLUSIONS: No significant
differences were observed in the extent of acute stent recoil between the Xience
Prime and the Promus Premier stent. A larger stent/vessel ratio, a larger
balloon/stent ratio, and direct stenting were associated with significant acute
stent recoil >=10%. (c) 2017 Wiley Periodicals, Inc.
PMID- 28500739
TI - Feasibility and safety of transfemoral sheathless portico aortic valve
implantation: Preliminary results in a single center experience.
AB - BACKGROUND: Feasibility of transfemoral (TF) transcathteter aortic valve
replacement (TAVR) is limited by the smallest diameter, the calcification and
tortuosity of the iliofemoral access vessels. The use of the Portico system
without delivery sheath results in significantly lower profile delivery system
compared to standard technique. We herein report our single center experience,
feasibility and safety of such an approach. METHODS: The Portico valve was
implanted sheathless in 81 high-risk patients with severe aortic stenosis
utilizing percutaneous femoral access. Mean minimal diameter of the ileo-femoral
arterial access was 7.06 +/- 1.89 mm. In most cases a multidetector computed
tomography was performed before the intervention to assess the feasibility of
vascular access and for aortic annulus measurements. The vascular access site was
preclosed using two ProGlide suture systems. RESULTS: Device implantation was
successful 98.7% of patients. Valve recapturing and repositioning as well as
valve-in-valve deployment was performed in only one case (1.2%). There were no
infarctions, 2 strokes (2.4%) and 2 acute kidney failure (2.4%), 1 major vascular
complication1 (1.2%) 4 major bleedings (4.9%), 11 conductions disturbances and
relative pace-maker implantations (14.2%). The mean gradient decreased from 42.3
+/- 17 to 6.3 +/- 2.78 mm Hg. Paravalvular regurgitation as assessed by TTE at
discharge was absent or trivial in 19 patients, mild in 60 and moderate 1. Thirty
day mortality was 2.4%. CONCLUSIONS: Sheathless use of the Portico valve is
feasible and appears to be safe, with excellent rates of complications and
mortality in the short-term. Such an approach has the potential to further expand
feasibility of TF TAVR to patients with severe peripheral arterial disease.
Feasibility in patients with smaller femoral access and more challenging anatomy
has to be proven in further studies. (c) 2017 Wiley Periodicals, Inc.
PMID- 28500737
TI - Clinical outcomes of overlapping versus non-overlapping everolimus-eluting absorb
bioresorbable vascular scaffolds: An analysis from the multicentre prospective
RAI registry (ClinicalTrials.gov identifier: NCT02298413).
AB - OBJECTIVES: To compare clinical outcomes of patients treated with overlapping
versus non-overlapping Absorb BVS. BACKGROUND: Limited data are available on the
clinical impact of stent overlap with the Absorb BVS bioresorbable stent.
METHODS: We compared outcomes of patients receiving overlapping or non
overlapping Absorb BVS in the multicenter prospective RAI Registry. RESULTS: Out
of 1,505 consecutive patients treated with Absorb BVS, 1,384 were eligible for
this analysis. Of these, 377 (27%) were in the overlap group, and 1,007 (73%) in
the non-overlap group. The most frequent overlap configuration was the marker-to
marker type (48%), followed by marker-over-marker (46%) and marker-inside-marker
(6%) types. Patients of the overlap group had higher prevalence of multivessel
disease and higher SYNTAX score, and required more frequently the use of
intravascular imaging. At a median follow-up of 368 days, no difference was
observed between overlap and non-overlap groups in terms of a device-related
composite endpoint (cardiac death, TV-MI, ID-TLR) (5.8% vs. 4.1%, P = 0.20) or of
a patient-related composite endpoint (any death, any MI, any revascularization)
(15.4% vs. 12.5%, P = 0.18). Cardiac death (1.0% vs. 1.3%, P = 0.54), MI (4.5%
vs. 3.6%, P = 0.51), TVR (4.5% vs. 3.6%, P = 0.51) and stent thrombosis (1.1 vs.
1.5%, P = 1.00) were also comparable between groups. When assessing outcomes of
the overlap population according to overlap configurations used, no difference
was observed in terms of the device- or patient-related composite endpoints.
CONCLUSIONS: Outcomes of patients with or without overlapping BVS were comparable
at mid-term follow-up despite higher angiographic complexity of the overlap
subset. (c) 2017 Wiley Periodicals, Inc.
PMID- 28500740
TI - Children with low-risk acute lymphoblastic leukemia are at highest risk of second
cancers.
AB - BACKGROUND: The improved survival rates for childhood acute lymphoblastic
leukemia (ALL) may be jeopardized by the development of a second cancer, which
has been associated with thiopurine therapy. PROCEDURE: We retrospectively
analyzed three sequential Nordic Society of Paediatric Haematology and Oncology's
protocols characterized by increasing intensity of thiopurine-based maintenance
therapy. We explored the risk of second cancer in relation to protocols, risk
group, thiopurine methyltransferase (TPMT) activity, ALL high hyperdiploidy
(HeH), and t(12;21)[ETV6/RUNX1]. RESULTS: After median 9.5 years (interquartile
range, 5.4-15.3 yrs) of follow-up, 40 of 3,591 patients had developed a second
cancer, of whom 38 had non-high-risk B-cell precursor ALL. Patients with standard
risk ALL, who received the longest maintenance therapy, had the highest adjusted
hazard of second cancer (hazard ratio [HR], intermediate vs. standard risk: 0.16,
95% CI: 0.06-0.43, P < 0.001; HR, high vs. standard risk: 0.09, 95% CI: 0.02
0.49, P = 0.006); no significant effects of protocol, age, or white blood cell
count at diagnosis, ALL HeH, or t(12;21)[ETV6/RUNX1] were observed. A subset
analysis on the patients with standard-risk ALL did not show an increased hazard
of second cancer from either HeH or t(12;21) (adjusted HR 2.02, 95% CI: 0.69
5.96, P = 0.20). The effect of low TPMT low activity was explored in patients
reaching maintenance therapy in clinical remission (n = 3,368); no association
with second cancer was observed (adjusted HR 1.43, 95% CI: 0.54-3.76, P = 0.47).
CONCLUSIONS: The rate of second cancer was generally highest in patients with low
risk ALL, but we could not identify a subset at higher risk than others.
PMID- 28500741
TI - Mouth examination performance by children's parents and by adolescents in Fanconi
anemia.
AB - BACKGROUND: Fanconi anemia (FA) is a rare genetic syndrome characterized by
increased risk of developing malignant neoplasms, particularly oral squamous cell
carcinoma. This study aims to ascertain the extent to which adolescents and
guardians/parents of children with FA are aware of their oral cancer risks and
assess their ability to perform mouth examination (ME). PROCEDURE: A cross
sectional study was conducted among patients with FA (between 6 and 16 years) and
their parents. A total of 45 patients, 19 children and 26 adolescents,
participated in the study. Among children less than 12 years of age, caregivers
performed ME and adolescents between 12 and 16 years of age performed mouth self
examination (MSE). All parents were given a self-reporting questionnaire to
collect sociodemographic data, information about health-related behaviors, and
oral cancer awareness. Performance was evaluated using criteria for mucosal
visualization and retracting ability. Subsequently, a dentist clinically examined
all patient participants. RESULTS: Performance evaluation indicated that the
examination quality was unsatisfactory in both groups. Statistical significance
was found between ability to perform ME by marital status (P < 0.036), where
divorced parents had more difficulty performing ME than nondivorced parents.
CONCLUSION: Oral mucosa surveillance performed by parents and adolescents seems
to be inaccurate. However, as an oral examination is a relatively inexpensive
form of secondary prevention, it merits attention to teaching the technique to
patients with FA and their caregivers.
PMID- 28500742
TI - Amino acids at positions 3, 168, and 169 are associated with the ability of Nef
proteins from HIV-1 CRF01_AE to downmodulate CD4.
AB - Several HIV-1 subtypes are co-circulating among various high-risk groups in
China, and an increasing prevalence of CRF01_AE was observed among MSM (men who
have sex with men) within recent years. Patients infected with CRF01_AE may
experience a more rapid disease progression than patients infected with non
CRF01_AE; however, the underlying mechanisms remains elusive. HIV-1 Nef is a
multifunctional protein and plays critical roles in viral pathogenesis. Nef
downregulates CD4 and human leukocyte antigen (HLA) to promote viral transmission
and escape from the host immune response. In this study, we investigated the CD4
downmodulation activity of Nef proteins isolated from HIV-1 CRF01_AE and analyzed
a potential relationship of Nef's capacity to downregulate CD4 with disease
progression. We found that the majority of these Nefs from HIV-1 CRF01_AE
efficiently downregulated CD4; Nefs with weaker CD4 downmodulation activity
tended to be associated with higher CD4 levels and lower viral loads. Further
elucidation revealed that amino acid residues at positions 3, 168, and 169 of
CRF01_AE Nefs were associated with the capacity to downregulate CD4. Our data
suggest that the capacity of Nef-mediated CD4 downregulation is not the only
determinant for controlling disease progression, and other host and viral factors
should be considered to explain the rapid disease progression of patients
infected with HIV-1 CRF01_AE.
PMID- 28500743
TI - Safety and efficacy of clip-based vs. suture mediated vascular closure for
femoral access hemostasis: A prospective randomized single center study comparing
the StarClose and the ProGlide device.
AB - OBJECTIVES: This study is the first head-to-head analysis of StarClose vs.
ProGlide in patients undergoing 5F or 6F percutaneous coronary catheterization or
peripheral artery interventions. BACKGROUND: The clip based StarClose and the
suture mediated ProGlide vascular closure device are well established for femoral
hemostasis in endovascular therapy. However, until now no prospective randomized
study compared the safety and efficacy of the two devices. METHODS: This
prospective, randomized, single-center study enrolled 505 patients (69.6 +/- 11.2
years) resulting in 538 procedures due to more than one intervention in several
patients: We analyzed 422 cardiac catheterization and 116 peripheral artery
interventions via a common femoral artery access. Patients were randomized to
StarClose or ProGlide (1:1). In-hospital complications (major bleeding, hematoma,
pseudoaneurysm, vessel occlusion, and arteriovenous fistula) and device failure
were recorded. The puncture site was assessed by ultrasound in all patients prior
to discharge. RESULTS: Overall complication rate was 3.9%. There were more
complications after utilization of StarClose compared to ProGlide (5.6 vs. 2.2%,
P = 0.064), which was significant in adjusted logistic regression analysis with a
2.9-fold increased risk of complications for StarClose (P < 0.05). In the
subgroup of coronary catheterizations there were significantly more complications
for StarClose compared to ProGlide (1.4 vs. 5.2%, P < 0.05) with a 4.7-fold
increased risk. Device failure rate was not significantly different between the
two devices. CONCLUSION: In this first randomized trial comparing the two closure
systems complication rate was higher for StarClose with equal efficacy compared
to ProGlide. (c) 2017 Wiley Periodicals, Inc.
PMID- 28500744
TI - Risk of cataract among interventional cardiologists and catheterization lab
staff: A systematic review and meta-analysis.
AB - OBJECTIVES: We performed a systematic review and meta-analysis to assess the risk
of developing a radiation-induced cataract in interventional cardiologists (ICs).
BACKGROUND: ICs are forced to radiation exposure during cardiac catheterization
procedures. Since the eye lens is one of the most radiosensitive organs in the
body, ICs are highly susceptible to develop a radiation-induced cataract. METHOD:
We performed a systematic literature search of nine electronic databases to
retrieve studies that report cataract among interventional cardiologists. Records
were screened for eligibility and data were extracted and analyzed using review
manager (RevMan) for windows. RESULTS: Eight studies involving 2559 subjects
(exposed ICs = 1224) were included. Posterior lens opacity was significantly
higher in ICs relative to the control group (RR= 3.21, 95% CI [2.14, 4.83], P <
0.00001). In contrast, there was no significant difference between both groups in
cortical lens opacity (RR= 0.69, 95% CI [0.46, 1.06], P = 0.09) and nuclear
opacity (RR= 0.85, 95% CI [0.71, 1.02], P = 0.08). CONCLUSION: Interventional
cardiologists are at high risk of developing radiation-induced cataract;
therefore, protective measures with high safety rates should be implied. (c) 2017
Wiley Periodicals, Inc.
PMID- 28500745
TI - Advanced oxidation protein products induce hepatocyte epithelial-mesenchymal
transition via a ROS-dependent, TGF-beta/Smad signaling pathway.
AB - Epithelial-mesenchymal transition (EMT) occurs during the progression of liver
fibrosis in response to chronic liver injury. However, the molecular mechanism
underlying the regulation of hepatocyte EMT remains unclear. The aim of this
study was to determine whether advanced oxidation protein products (AOPP) had an
effect on hepatocyte EMT. The human L02 hepatocyte cell line and hepatocytes from
normal Sprague-Dawley rats were challenged with AOPP treatment in both in vitro
and in vivo studies. The expression of cell and molecular markers of EMT in L02
hepatocytes were studied using Western blotting, and quantitative reverse
transcription-polymerase chain reaction (qRT-PCR) assays. Hepatocyte migratory
potential was analyzed using a wound healing assay. Intracellular reactive oxygen
species (ROS) were detected using the dichlorofluorescein (DCF) assay. In liver
tissue sections, expression of EMT markers was evaluated using
immunohistochemistry, and collagen was assessed using histochemical staining with
Masson's trichrome. The findings were that AOPP treatment resulted in EMT in
hepatocytes, which was associated with reduced expression of E-cadherin,
increased expression of vimentin, increased deposition of collagen protein, and
enhanced cell migration in vivo and in vitro. AOPP was also found to promote
migration in L02 cells, and to promote the production of ROS and the activation
of TGF-betaR and Smad signaling. Inhibition of the generation of intracellular
ROS and TGF-beta receptor blocking could reverse AOPP-induced EMT in hepatocytes.
This study has identified a novel mechanism in the regulation of hepatocyte EMT,
and the findings may have implications for the control of liver fibrosis.
PMID- 28500746
TI - Higher viral load and genetic diversity of HIV-1 in seminal compartments than in
blood of seven Chinese men who have sex with men and have early HIV-1 infection.
AB - To date, there have been no reports characterizing HIV-1 in the semen of Chinese
men who have sex with men (MSM) with early infection. In this study, genetic
diversity and viral load of HIV-1 in the seminal compartments and blood of
Chinese MSM with early HIV-1 infection were examined. Viral load and genetic
diversity of HIV-1 in paired samples of semen and blood were analyzed in seven
MSM with early HIV-1 infection. HIV-1 RNA and DNA were quantitated by real-time
PCR assays. Through sequencing the C2-V5 region of the HIV-1 env gene, the HIV-1
genotype and genetic diversity based on V3 loop amino acid sequences were
determined by using Geno2pheno and PSSM programs co-receptor usage. It was found
that there was more HIV-1 RNA in seminal plasma than in blood plasma and total,
and more 2-LTR circular and integrated HIV-1 DNA in seminal cells than in
peripheral blood mononuclear cells from all seven patients with early HIV
infection. There was also greater HIV-1 genetic diversity in seminal than in
blood compartments. HIV-1 in plasma displayed higher genetic diversity than in
cells from the blood and semen. In addition, V3 loop central motifs, which
present some key neutralizing antibody epitopes, varied between blood and semen.
Thus, virological characteristics in semen may be more representative when
evaluating risk of transmission in persons with early HIV infection.
PMID- 28500747
TI - Investigating biogeographic boundaries of the Sunda shelf: A phylogenetic
analysis of two island populations of Macaca fascicularis.
AB - OBJECTIVES: Cyclical submergence and re-emergence of the Sunda Shelf throughout
the Pleistocene served as a dynamic biogeographic landscape, across which long
tailed macaques (Macaca fascicularis) have migrated and evolved. Here, we tested
the integrity of the previously reported continental-insular haplotype divide
reported among Y and mitochondrial DNA lineages across multiple studies.
MATERIALS AND METHODS: The continental-insular haplotype divide was tested by
heavily sampling wild macaques from two important biogeographic regions within
Sundaland: (1) Singapore, the southernmost tip of continental Asia and (2) Bali,
Indonesia, the southeastern edge of the Indonesian archipelago, immediately west
of Wallace's line. Y DNA was haplotyped for samples from Bali, deep within the
Indonesian archipelago. Mitochondrial D-loop from both islands was analyzed
against existing data using Maximum Likelihood and Bayesian approaches. RESULTS:
We uncovered both "continental" and "insular" Y DNA haplotypes in Bali. Between
Singapore and Bali we found 52 unique mitochondrial haplotypes, none of which had
been previously described. Phylogenetic analyses confirmed a major haplogroup
division within Singapore and identified five new Singapore subclades and two
primary subclades in Bali. DISCUSSION: While we confirmed the continental-insular
divide among mtDNA haplotypes, maintenance of both Y DNA haplotypes on Bali, deep
within the Indonesian archipelago calls into question the mechanism by which Y
DNA diversity has been maintained. It also suggests the continental-insular
designation is less appropriate for Y DNA, leading us to propose geographically
neutral Y haplotype designations.
PMID- 28500748
TI - Epidemiology and genetic diversity of classic human astrovirus among hospitalized
children with acute gastroenteritis in Uruguay.
AB - Classic Human Astrovirus (Classic HAstV) are one of the most important causes of
pediatric acute gastroenteritis (AGE), after rotaviruses and arguably
caliciviruses. The aim of this study was to determine the molecular epidemiology
of Classic HAstV from 175 clinical samples, being 153 stools and 22 vomits,
collected from pediatric hospitalized patients with AGE in Salto city, Uruguay,
from January 2011 to December 2012. Classic HAstV were detected and genotyped by
using a qualitative Retro Transcription-Polimerase Chain Reaction (RT-PCR)
directed to the Open Reading Frame-2 (ORF2) region C. Amplicons were sequenced
and phylogenetic analyses were carried out in order to determine genotypes and
lineages. Classic HAstV were detected in 18 out of 175 analyzed samples (10.3%)
and 14 of them (78.0%) were successfully sequenced being 6 (42.8%) classified as
HAstV-1 (1a lineage), 4 (28.6%) as HAstV-2 (2c lineage), and 4 (28.6%) as HAstV-3
(3c lineage). A higher detection of Classic HAstV infections was observed in
autumn for both years of surveillance, and the majority of the positive cases
were observed in 2011. The group of children between 2 and 5 years old presented
the higher percentage of infections. To our knowledge, the present study
represents the first report of astrovirus from acute gastroenteritis cases in
Uruguay, evidencing its role as a relevant etiologic agent in severe cases of
this disease.
PMID- 28500749
TI - Local resectability assessment of head and neck cancer: Positron emission
tomography/MRI versus positron emission tomography/CT.
AB - BACKGROUND: The purpose of this study was to compare the diagnostic accuracy of
positron emission tomography (PET)/MRI with PET/CT for local resectability of
head and neck cancer. METHODS: Sequential contrast-enhanced PET/CT-MRI was
performed in 58 patients referred for the staging or restaging of head and neck
cancer. Tumors were assessed with PET/CT and PET/MRI for the presence of
resectability-defining factors: T4b status (mediastinal invasion, invasion of the
prevertebral space, and vascular encasement), and another 8 findings that would
imply obstacles for surgical cure (invasion of the laryngeal cartilage, invasion
of the preepiglottic fat pad, perineural spread, orbital invasion, bone
infiltration, skull base invasion, dural infiltration, and invasion of the
brachial plexus). RESULTS: The sensitivity/specificity/accuracy of local
resectability-defining factors of PET/CT and PET/MRI was 0.92/0.99/0.98 and
0.98/0.99/0.99 (P = .727), respectively, per lesion, and 0.96/0.87/0.91 and
0.96/0.90/0.93 (P = .687), respectively, per patient. CONCLUSION: Both contrast
enhanced PET/MRI and contrast-enhanced PET/CT can serve as reliable examinations
for defining local resectability of head and neck cancer.
PMID- 28500750
TI - Nausea and vomiting in children and adolescents receiving intrathecal
methotrexate: A prospective, observational study.
AB - BACKGROUND: The prevalence of nausea and vomiting after receipt of intrathecal
methotrexate (IT-MTX) in pediatric oncology patients is unknown. METHODS:
Patients (4-18 years) about to receive IT-MTX were eligible to participate in
this prospective, observational study. Patients received antiemetics as
prescribed by their clinical team. Nausea severity (patient-assessed), timing of
emetic episodes, and administration of antiemetics were recorded beginning
immediately prior to IT-MTX administration, for the next 24 hr (acute phase), and
for a maximum of 7 additional days (delayed phase). Complete chemotherapy-induced
nausea and vomiting (CINV) control was defined as no emetic episodes and no
nausea. RESULTS: One hundred patients consented to participate in this study; 70
provided evaluable data (mean age: 8.3 years; range: 4.1-17.6). Most (94%)
received propofol-containing anesthesia for IT-MTX administration. Most (89%)
received a 5-HT3 antagonist prior to IT-MTX. During the acute phase, 36 children
(51%) experienced complete CINV control, 67 (96%) complete vomiting control, and
36 (51%) complete nausea control. Severe acute phase nausea was reported by 12
children (17%). During the delayed phase, 35 patients (50%) experienced complete
CINV control, 60 (86%) complete vomiting control, and 36 (51%) complete nausea
control. Severe nausea was reported in the delayed phase by 27 (39%) patients.
CONCLUSIONS: Most pediatric patients who received IT-MTX and prophylaxis with
ondansetron or granisetron experienced complete acute and delayed vomiting
control. However, nausea control was poor and severe nausea was reported by many
children. Effective interventions to control nausea are needed.
PMID- 28500753
TI - A 0-Hour/1-Hour Protocol for Safe, Early Discharge of Chest Pain Patients.
AB - OBJECTIVES: Guidelines recommend a 0-hour/1-hour high-sensitivity cardiac
troponin T (hs-cTnT) diagnostic strategy in acute chest pain patients. There are,
however, little data on the performance of this strategy when combined with
clinical risk stratification. We aimed to evaluate the diagnostic accuracy of an
accelerated diagnostic protocol (ADP) using the 0-hour/1-hour hs-cTnT strategy
together with an adapted Thrombolysis In Myocardial Infarction (TIMI) score and
electrocardiogram (ECG) for ruling out major adverse cardiac events (MACE) within
30 days. METHODS: This prospective observational study enrolled consecutive
emergency department (ED) chest pain patients. TIMI score variables, ED
physicians' assessments of the ECG, and 0- and 1-hour hs-cTnT were collected.
Thirty-day MACE was defined as acute myocardial infarction (AMI), unstable angina
(UA), cardiogenic shock, ventricular arrhythmia, atrioventricular block, cardiac
arrest, or death of cardiac or unknown cause. RESULTS: A total of 1,020 patients
were included in the final analysis. The combination of an adapted TIMI score
<=1, a nonischemic ECG, and either a 0-hour hs-cTnT < 5 ng/L or a 0-hour hs-cTnT
< 12 ng/L combined with a 1-hour increase < 3 ng/L identified 432 (42.4%)
patients as very low risk with a negative predictive value of 99.5% (95%
confidence interval [CI] = 98.3%-99.9%) and a negative likelihood ratio of 0.04
(95% CI = 0.01-0.14) for 30-day MACE. The ADP missed only two patients with UA
and no patients with AMI or other forms of MACE. CONCLUSION: An ADP using the
guideline recommended 0-hour/1-hour hs-cTnT strategy rapidly identified patients
with a very low risk of 30-day MACE including UA where no further cardiac testing
would be needed. This could potentially allow safe early discharge of about 40%
of ED chest pain patients.
PMID- 28500754
TI - Mutational phospho-mimicry reveals a regulatory role for the XRCC4 and XLF C
terminal tails in modulating DNA bridging during classical non-homologous end
joining.
AB - XRCC4 and DNA Ligase 4 (LIG4) form a tight complex that provides DNA ligase
activity for classical non-homologous end joining (the predominant DNA double
strand break repair pathway in higher eukaryotes) and is stimulated by XLF.
Independently of LIG4, XLF also associates with XRCC4 to form filaments that
bridge DNA. These XRCC4/XLF complexes rapidly load and connect broken DNA,
thereby stimulating intermolecular ligation. XRCC4 and XLF both include
disordered C-terminal tails that are functionally dispensable in isolation but
are phosphorylated in response to DNA damage by DNA-PK and/or ATM. Here we
concomitantly modify the tails of XRCC4 and XLF by substituting fourteen
previously identified phosphorylation sites with either alanine or aspartate
residues. These phospho-blocking and -mimicking mutations impact both the
stability and DNA bridging capacity of XRCC4/XLF complexes, but without affecting
their ability to stimulate LIG4 activity. Implicit in this finding is that
phosphorylation may regulate DNA bridging by XRCC4/XLF filaments.
PMID- 28500755
TI - Enhanced FIB-SEM systems for large-volume 3D imaging.
AB - Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) can automatically
generate 3D images with superior z-axis resolution, yielding data that needs
minimal image registration and related post-processing. Obstacles blocking wider
adoption of FIB-SEM include slow imaging speed and lack of long-term system
stability, which caps the maximum possible acquisition volume. Here, we present
techniques that accelerate image acquisition while greatly improving FIB-SEM
reliability, allowing the system to operate for months and generating
continuously imaged volumes > 106 um3. These volumes are large enough for
connectomics, where the excellent z resolution can help in tracing of small
neuronal processes and accelerate the tedious and time-consuming human
proofreading effort. Even higher resolution can be achieved on smaller volumes.
We present example data sets from mammalian neural tissue, Drosophila brain, and
Chlamydomonas reinhardtii to illustrate the power of this novel high-resolution
technique to address questions in both connectomics and cell biology.
PMID- 28500757
TI - Meta-analysis of the effect of the maternal vitamin D level on the risk of
spontaneous pregnancy loss.
AB - BACKGROUND: The association between vitamin D deficiency and early spontaneous
pregnancy loss (SPL) is unclear. OBJECTIVES: To assess the association of serum
25-hydroxyvitamin D (25(OH)D) and SPL. SEARCH STRATEGY: Embase, PubMed, and Web
of Science were searched for relevant papers published before February 20, 2016,
using search terms including "vitamin D" and "pregnancy loss." SELECTION
CRITERIA: Case-control and cohort studies investigating the relationship of
maternal serum 25(OH)D and SPL were included. DATA COLLECTION AND ANALYSIS: Two
authors independently extracted original data from the selected papers. The
DerSimonian-Laird random-effects model was used to perform the meta-analysis.
Heterogeneity was assessed by calculating I2 . MAIN RESULTS: Five studies,
including 10 630 pregnant women, met the inclusion criteria. There was no
significant association between a low 25(OH)D level and an increased risk of SPL.
In a subgroup analysis, an extremely low 25(OH)D level (<20 ng/mL) was
significantly associated with an increased risk of SPL in the first trimester
(relative risk 2.24, 95% confidence interval 1.15-4.37); the heterogeneity across
studies was not significant (I2 =0.0%, P=0.355). CONCLUSIONS: Severe Vitamin D
deficiency could be detrimental to early embryonic development and increase the
risk of early SPL.
PMID- 28500756
TI - Sphingomyelin metabolism controls the shape and function of the Golgi cisternae.
AB - The flat Golgi cisterna is a highly conserved feature of eukaryotic cells, but
how is this morphology achieved and is it related to its function in cargo
sorting and export? A physical model of cisterna morphology led us to propose
that sphingomyelin (SM) metabolism at the trans-Golgi membranes in mammalian
cells essentially controls the structural features of a Golgi cisterna by
regulating its association to curvature-generating proteins. An experimental test
of this hypothesis revealed that affecting SM homeostasis converted flat
cisternae into highly curled membranes with a concomitant dissociation of
membrane curvature-generating proteins. These data lend support to our hypothesis
that SM metabolism controls the structural organization of a Golgi cisterna.
Together with our previously presented role of SM in controlling the location of
proteins involved in glycosylation and vesicle formation, our data reveal the
significance of SM metabolism in the structural organization and function of
Golgi cisternae.
PMID- 28500752
TI - Which ante mortem clinical features predict progressive supranuclear palsy
pathology?
AB - BACKGROUND: Progressive supranuclear palsy (PSP) is a neuropathologically defined
disease presenting with a broad spectrum of clinical phenotypes. OBJECTIVE: To
identify clinical features and investigations that predict or exclude PSP
pathology during life, aiming at an optimization of the clinical diagnostic
criteria for PSP. METHODS: We performed a systematic review of the literature
published since 1996 to identify clinical features and investigations that may
predict or exclude PSP pathology. We then extracted standardized data from
clinical charts of patients with pathologically diagnosed PSP and relevant
disease controls and calculated the sensitivity, specificity, and positive
predictive value of key clinical features for PSP in this cohort. RESULTS: Of
4166 articles identified by the database inquiry, 269 met predefined standards.
The literature review identified clinical features predictive of PSP, including
features of the following 4 functional domains: ocular motor dysfunction,
postural instability, akinesia, and cognitive dysfunction. No biomarker or
genetic feature was found reliably validated to predict definite PSP. High
quality original natural history data were available from 206 patients with
pathologically diagnosed PSP and from 231 pathologically diagnosed disease
controls (54 corticobasal degeneration, 51 multiple system atrophy with
predominant parkinsonism, 53 Parkinson's disease, 73 behavioral variant
frontotemporal dementia). We identified clinical features that predicted PSP
pathology, including phenotypes other than Richardson's syndrome, with varying
sensitivity and specificity. CONCLUSIONS: Our results highlight the clinical
variability of PSP and the high prevalence of phenotypes other than Richardson's
syndrome. The features of variant phenotypes with high specificity and
sensitivity should serve to optimize clinical diagnosis of PSP. (c) 2017
International Parkinson and Movement Disorder Society.
PMID- 28500758
TI - MSCs ameliorates DPN induced cellular pathology via [Ca2+ ]i homeostasis and
scavenging the pro-inflammatory cytokines.
AB - The MSCs of various origins are known to ameliorate or modulate cell survival
strategies. We investigated, whether UCB MSCs could improve the survival of the
human neuronal cells and/or fibroblast assaulted with DPN sera. The results
showed, the co-culture of UCB MSCs with human neuronal cells and/or fibroblasts
could effectively scavenge the pro-inflammatory cytokines TNF-alpha, IL-1beta,
IFN-? and IL - 12 and control the pro-apoptotic expression of p53/Bax. Further co
culture of UCB MSCs have shown to induce anti-inflammatory cytokines like IL-4,
IL-10 and TGF-beta and anti-apoptotic Bclxl/Bcl2 expression in the DPN sera
stressed cells. Amelioration of elevated [Ca2+ ]i and cROS, the portent behind
the NFkappaB/Caspase-3 mediated inflammation in DPN rescued the cells from
apoptosis. The results of systemic administration of BM MSCs improved DPN
pathology in rat as extrapolated from human cell model. The BM MSCs ameliorated
prolonged distal motor latency (control: 0.70 +/- 0.06, DPN: 1.29 +/- 0.13 m/s
DPN + BM MSCs: 0.89 +/- 0.02 m/s, p < 0.05) and lowered high amplitude of
compound muscle action potentials (CMAPs) (control: 12.36 +/- 0.41, DPN: 7.52 +/-
0.61 mV, DPN + MSCs: 8.79 +/- 0.53 mV, p < 0.05), while slowly restoring the
plasma glucose levels. Together, all these results showed that administration of
BM or UCB MSCs improved the DPN via ameliorating pro-inflammatory cytokine
signaling and [Ca2+ ]i homeostasis.
PMID- 28500751
TI - Radiological biomarkers for diagnosis in PSP: Where are we and where do we need
to be?
AB - PSP is a pathologically defined neurodegenerative tauopathy with a variety of
clinical presentations including typical Richardson's syndrome and other variant
PSP syndromes. A large body of neuroimaging research has been conducted over the
past two decades, with many studies proposing different structural MRI and
molecular PET/SPECT biomarkers for PSP. These include measures of brainstem,
cortical and striatal atrophy, diffusion weighted and diffusion tensor imaging
abnormalities, [18F] fluorodeoxyglucose PET hypometabolism, reductions in
striatal dopamine imaging and, most recently, PET imaging with ligands that bind
to tau. Our aim was to critically evaluate the degree to which structural and
molecular neuroimaging metrics fulfill criteria for diagnostic biomarkers of PSP.
We queried the PubMed, Cochrane, Medline, and PSYCInfo databases for original
research articles published in English over the past 20 years using postmortem
diagnosis or the NINDS-SPSP criteria as the diagnostic standard from 1996 to
2016. We define a five-level theoretical construct for the utility of
neuroimaging biomarkers in PSP, with level 1 representing group-level findings,
level 2 representing biomarkers with demonstrable individual-level diagnostic
utility, level 3 representing biomarkers for early disease, level 4 representing
surrogate biomarkers of PSP pathology, and level 5 representing definitive PSP
biomarkers of PSP pathology. We discuss the degree to which each of the currently
available biomarkers fit into this theoretical construct, consider the role of
biomarkers in the diagnosis of Richardson's syndrome, variant PSP syndromes and
autopsy confirmed PSP, and emphasize current shortfalls in the field. (c) 2017
The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of
International Parkinson and Movement Disorder Society.
PMID- 28500760
TI - The opposite effects of nitric oxide donor, S-nitrosoglutathione, on myocardial
ischaemia/reperfusion injury in diabetic and non-diabetic mice.
AB - Nitric oxide is a potent anti-apoptotic and cardioprotective molecule in healthy
animals. However, recent study demonstrates that overexpression of eNOS
exacerbates the liver injury in diabetic animals. whether diabetes may also alter
NO's biologic activity in ischaemic/reperfused heart remains unknown. The present
experiment was designed to determine whether the nitric oxide donor, S
nitrosoglutathione, may exert different effects on diabetic and non-diabetic
myocardial ischaemia/reperfusion (MI/R) injury. Diabetic state was induced in
mice by multiple intraperitoneal injections of low-dose streptozotocin (STZ). The
control or diabetic mice were subjected to 30 minutes ischaemia and 3 or 24 hours
reperfusion. At 10 minutes before reperfusion, diabetic and non-diabetic mice
were received an intraperitoneal injection of S-nitrosoglutathione (GSNO, a
nitric oxide donor, 1 MUmol/kg). GSNO attenuated MI/R injury in non-diabetic
mice, as measured by improved cardiac function, reduced infarct size and
decreased cardiomyocyte apoptosis. In contrast, GSNO failed to attenuate but,
rather, aggravated the MI/R injury in diabetic mice. Mechanically, the diabetic
heart exhibited an increased nitrative/oxidative stress level, as measured by
peroxynitrite formation, compared with non-diabetic mice. Co-administration of
GSNO with EUK134 (a peroxynitrite scavenger) or MnTE-2-PyP5 (a superoxide
dismutase mimetic) or Apocynin (a NADPH oxidase inhibitor) 10 minutes before
reperfusion significantly decreased the MI/R-induced peroxynitrite formation and
the MI/R injury. Collectively, the present study for the first time demonstrated
that diabetes may cause superoxide overproduction, increase NO inactivation and
peroxynitrite formation, and thus convert GSNO from a cardioprotective molecule
to a cardiotoxic molecule.
PMID- 28500759
TI - A Monte Carlo model for mean glandular dose evaluation in spot compression
mammography.
AB - PURPOSE: To characterize the dependence of normalized glandular dose (DgN) on
various breast model and image acquisition parameters during spot compression
mammography and other partial breast irradiation conditions, and evaluate
alternative previously proposed dose-related metrics for this breast imaging
modality. METHODS: Using Monte Carlo simulations with both simple homogeneous
breast models and patient-specific breasts, three different dose-related metrics
for spot compression mammography were compared: the standard DgN, the normalized
glandular dose to only the directly irradiated portion of the breast (DgNv), and
the DgN obtained by the product of the DgN for full field irradiation and the
ratio of the mid-height area of the irradiated breast to the entire breast area
(DgNM ). How these metrics vary with field-of-view size, spot area thickness, x
ray energy, spot area and position, breast shape and size, and system geometry
was characterized for the simple breast model and a comparison of the simple
model results to those with patient-specific breasts was also performed. RESULTS:
The DgN in spot compression mammography can vary considerably with breast area.
However, the difference in breast thickness between the spot compressed area and
the uncompressed area does not introduce a variation in DgN. As long as the spot
compressed area is completely within the breast area and only the compressed
breast portion is directly irradiated, its position and size does not introduce a
variation in DgN for the homogeneous breast model. As expected, DgN is lower than
DgNv for all partial breast irradiation areas, especially when considering spot
compression areas within the clinically used range. DgNM underestimates DgN by
6.7% for a W/Rh spectrum at 28 kVp and for a 9 * 9 cm2 compression paddle.
CONCLUSION: As part of the development of a new breast dosimetry model, a task
undertaken by the American Association of Physicists in Medicine and the European
Federation of Organizations of Medical Physics, these results provide insight on
how DgN and two alternative dose metrics behave with various image acquisition
and model parameters.
PMID- 28500761
TI - Melatonin ameliorates myocardial ischemia reperfusion injury through SIRT3
dependent regulation of oxidative stress and apoptosis.
AB - Sirtuins are a family of highly evolutionarily conserved nicotinamide adenine
nucleotide-dependent histone deacetylases. Sirtuin-3 (SIRT3) is a member of the
sirtuin family that is localized primarily to the mitochondria and protects
against oxidative stress-related diseases, including myocardial
ischemia/reperfusion (MI/R) injury. Melatonin has a favorable effect in
ameliorating MI/R injury. We hypothesized that melatonin protects against MI/R
injury by activating the SIRT3 signaling pathway. In this study, mice were
pretreated with or without a selective SIRT3 inhibitor and then subjected to MI/R
operation. Melatonin was administered intraperitoneally (20 mg/kg) 10 minutes
before reperfusion. Melatonin treatment improved postischemic cardiac contractile
function, decreased infarct size, diminished lactate dehydrogenase release,
reduced the apoptotic index, and ameliorated oxidative damage. Notably, MI/R
induced a significant decrease in myocardial SIRT3 expression and activity,
whereas the melatonin treatment upregulated SIRT3 expression and activity, and
thus decreased the acetylation of superoxide dismutase 2 (SOD2). In addition,
melatonin increased Bcl-2 expression and decreased Bax, Caspase-3, and cleaved
Caspase-3 levels in response to MI/R. However, the cardioprotective effects of
melatonin were largely abolished by the selective SIRT3 inhibitor 3-(1H-1,2,3
triazol-4-yl)pyridine (3-TYP), suggesting that SIRT3 plays an essential role in
mediating the cardioprotective effects of melatonin. In vitro studies confirmed
that melatonin also protected H9c2 cells against simulated ischemia/reperfusion
injury (SIR) by attenuating oxidative stress and apoptosis, while SIRT3-targeted
siRNA diminished these effects. Taken together, our results demonstrate for the
first time that melatonin treatment ameliorates MI/R injury by reducing oxidative
stress and apoptosis via activating the SIRT3 signaling pathway.
PMID- 28500762
TI - Methyl aminolevulinate photodynamic therapy combined with curettage debulking for
pigmented basal cell carcinoma.
PMID- 28500763
TI - Crosstalk Between Enzyme Matrix Metalloproteinases 2 and 9 and Regulatory T Cell
Immunity in the Global Burden of Atherosclerosis.
AB - Changes in immune and inflammatory responses may play a crucial role in the
development and progression of atherosclerosis, as an autoimmune, chronic and
progressive inflammatory disease. Immunological activity and vascular
inflammation during atherosclerosis can be modulated by autoimmune responses
against self-antigens, according to changeable risk factors (cholesterol,
oxidized low-density lipoprotein (ox-LDL) in the vascular wall, fatty acids,
etc.), and accompanied by accumulation of leucocytes and proinflammatory
cytokines, which stimulate the transcription of matrix metalloproteinases (MMPs),
whose concentration are increased in foam cell-rich regions. Regulatory T cells
(Tregs) represent a unique subpopulation of T cells specialized in the regulation
of immune response and in the suppression of proatherogenic T cells. The aim of
our study was to examine the interactions between the concentration of enzyme
matrix metalloproteinases 2 and 9 (MMP-2 and 9) in urine and the percentage of
Tregs in peripheral blood of two groups of patients: with carotid artery stenosis
(CAS), undergoing surgery and with mild atherosclerosis (A) from general
practice. The method of enzyme immunoassay (ELISA) was used to determine enzyme
MMP expression, and Tregs was examined by flow cytometric analysis. Our data have
showed a large increase in the enzyme MMP-2 and 9 in the urine of CAS and A
patients in comparison with healthy controls and indicated this method as an easy
marker for the monitoring of the development of atherosclerosis. Simultaneously,
the diminished number of Tregs in the same patients pointed the importance of
these regulatory mechanisms in the etiopathogenesis of atherosclerosis and
possible Tregs-mediated therapy.
PMID- 28500765
TI - Developing Bayesian networks from a dependency-layered ontology: A proof-of
concept in radiation oncology.
AB - PURPOSE: Bayesian networks (BNs) are graphical representations of probabilistic
knowledge that offer normative reasoning under uncertainty and are well suited
for use in medical domains. Traditional knowledge-based network development of BN
topology requires that modeling experts establish relevant dependency links
between domain concepts by searching and translating published literature,
querying domain experts, or applying machine learning algorithms on data. For
initial development these methods are time-intensive and this cost hinders the
growth of BN applications in medical decision making. Further, this approach
fails to utilize knowledge representation in medical fields to automate network
development. Our research alleviates the challenges surrounding BN modeling in
radiation oncology by leveraging an ontology based hub and spoke system for BN
construction. METHODS: We implement a hub and spoke system by developing (a) an
ontology of knowledge in radiation oncology (the hub) which includes dependency
semantics similar to BN relations and (b) a software tool that operates on
ontological semantics using deductive reasoning to create BN topologies (the
spokes). We demonstrate that network topologies built using the software are
terminologically consistent and form networks that are topologically compatible
with existing ones. We do this first by merging two different BN models for
prostate cancer radiotherapy prediction which contain domain cross terms. We then
use the logic to perform discovery of new causal chains between radiation
oncology concepts. RESULTS: From the radiation oncology (RO) ontology we
successfully reconstructed a previously published prostate cancer radiotherapy
Bayes net using up-to-date domain knowledge. Merging this model with another
similar prostate cancer model in the RO domain produced a larger, highly
interconnected model representing the expanded scope of knowledge available
regarding prostate cancer therapy parameters, complications, and outcomes. The
causal discovery resulted in an automatically-built causal network model of all
ontologized radiotherapy concepts between a 'Mucositis' complication and anatomic
tumor location. CONCLUSIONS: The proposed model building approach lowers barriers
to developing probabilistic models relevant to real-world clinical decision
making, and offers a solution to the consistency and compatibility problems.
Further, the knowledge representation in this work demonstrates potential for
broader radiation oncology applications outside of Bayes nets.
PMID- 28500764
TI - Phylogeny is a powerful tool for predicting plant biomass responses to nitrogen
enrichment.
AB - Increasing rates of anthropogenic nitrogen (N) enrichment to soils often lead to
the dominance of nitrophilic plant species and reduce plant diversity in natural
ecosystems. Yet, we lack a framework to predict which species will be winners or
losers in soil N enrichment scenarios, a framework that current literature
suggests should integrate plant phylogeny, functional tradeoffs, and nutrient co
limitation. Using a controlled fertilization experiment, we quantified biomass
responses to N enrichment for 23 forest tree species within the genus Eucalyptus
that are native to Tasmania, Australia. Based on previous work with these
species' responses to global change factors and theory on the evolution of plant
resource-use strategies, we hypothesized that (1) growth responses to N
enrichment are phylogenetically structured, (2) species with more resource
acquisitive functional traits have greater growth responses to N enrichment, and
(3) phosphorus (P) limits growth responses to N enrichment differentially across
species, wherein P enrichment increases growth responses to N enrichment more in
some species than others. We built a hierarchical Bayesian model estimating
effects of functional traits (specific leaf area, specific stem density, and
specific root length) and P fertilization on species' biomass responses to N,
which we then compared between lineages to determine whether phylogeny explains
variation in responses to N. In concordance with literature on N limitation, a
majority of species responded strongly and positively to N enrichment. Mean
responses ranged three-fold, from 6.21 (E. pulchella) to 16.87 (E. delegatensis)
percent increases in biomass per g N.m-2 .yr-1 added. We identified a strong
difference in responses to N between two phylogenetic lineages in the Eucalyptus
subgenus Symphyomyrtus, suggesting that shared ancestry explains variation in N
limitation. However, our model indicated that after controlling for phylogenetic
non-independence, eucalypt responses to N were not associated with functional
traits (although post-hoc analyses show a phylogenetic pattern in specific root
length similar to that of responses to N), nor were responses differentially
limited by P. Overall, our model results suggest that phylogeny is a powerful
predictor of winners and losers in anthropogenic N enrichment scenarios in
Tasmanian eucalypts, which may have implications for other species.
PMID- 28500767
TI - Metformin for high-altitude performance?
AB - Metformin has been introduced for treatment of type 2 diabetes but may also have
ergogenic properties at high altitude by improving muscle glycogen repletion.
However, very little information is available on potential risks associated with
the (mis)use of metformin by healthy people.
PMID- 28500766
TI - Melatonin inhibits neuronal dysfunction-associated with neuroinflammation by
atopic psychological stress in NC/Nga atopic-like mouse models.
AB - Atopic dermatitis (AD), also known as atopic eczema, is chronic pruritic skin
disease. AD can increase psychological stress as well, increasing glucocorticoid
release and exacerbating the associated symptoms. Chronic glucocorticoid
elevation disturbs neuroendocrine signaling and can induce neuroinflammation,
neurotoxicity, and cognitive impairment; however, it is unclear whether AD
related psychological stress elevates glucocorticoids enough to cause neuronal
damage. Therefore, we assessed the effects of AD-induced stress in a mouse AD
model. AD-related psychological stress increased astroglial and microglial
activation, neuroinflammatory cytokine expression, and markers of neuronal loss.
Notably, melatonin administration inhibited the development of skin lesions,
scratching behavior, and serum IgE levels in the model mice, and additionally
caused a significant reduction in corticotropin-releasing hormone responsiveness,
and a significant reduction in neuronal damage. Finally, we produced similar
results in a corticosterone-induced AD-like skin model. This is the first study
to demonstrate that AD-related psychological stress increases neuroendocrine
dysfunction, exacerbates neuroinflammation, and potentially accelerates other
neurodegenerative disease states.
PMID- 28500768
TI - Can constitutive pigmentation be measured on upper inner arm? Correlation between
arm and buttocks pigmentation.
PMID- 28500769
TI - Biogeochemistry drives diversity in the prokaryotes, fungi, and invertebrates of
a Panama forest.
AB - Humans are both fertilizing the world and depleting its soils, decreasing the
diversity of aquatic ecosystems and terrestrial plants in the process. We know
less about how nutrients shape the abundance and diversity of the prokaryotes,
fungi, and invertebrates of Earth's soils. Here we explore this question in the
soils of a Panama forest subject to a 13-yr fertilization with factorial
combinations of nitrogen (N), phosphorus (P), and potassium (K) and a separate
micronutrient cocktail. We contrast three hypotheses linking biogeochemistry to
abundance and diversity. Consistent with the Stress Hypothesis, adding N
suppressed the abundance of invertebrates and the richness of all three groups of
organisms by ca. 1 SD or more below controls. Nitrogen addition plots were 0.8 pH
units more acidic with 18% more exchangeable aluminum, which is toxic to both
prokaryotes and eukaryotes. These stress effects were frequently reversed,
however, when N was added with P (for prokaryotes and invertebrates) and with
added K (for fungi). Consistent with the Abundance Hypothesis, adding P generally
increased prokaryote and invertebrate diversity, and adding K enhanced
invertebrate diversity. Also consistent with the Abundance Hypothesis, increases
in invertebrate abundance generated increases in richness. We found little
evidence for the Competition Hypothesis: that single nutrients suppressed
diversity by favoring a subset of high nutrient specialists, and that nutrient
combinations suppressed diversity even more. Instead, combinations of nutrients,
and especially the cation/micronutrient treatment, yielded the largest increases
in richness in the two eukaryote groups. In sum, changes in soil biogeochemistry
revealed a diversity of responses among the three dominant soil groups, positive
synergies among nutrients, and-in contrast with terrestrial plants-the frequent
enhancement of soil biodiversity.
PMID- 28500770
TI - The role of melatonin in the neurodevelopmental etiology of schizophrenia: A
study in human olfactory neuronal precursors.
AB - Dim light exposure of the mother during pregnancy has been proposed as one of the
environmental factors that affect the fetal brain development in schizophrenia.
Melatonin circulating levels are regulated by the environmental light/dark cycle.
This hormone stimulates neuronal differentiation in the adult brain. However,
little is known about its role in the fetal human brain development. Olfactory
neuronal precursors (ONPs) are useful for studying the physiopathology of
neuropsychiatric diseases because they mimic all the stages of neurodevelopment
in culture. Here, we first characterized whether melatonin stimulates neuronal
differentiation in cloned ONPs obtained from a healthy control subject (HCS).
Then, melatonin effects were evaluated in primary cultures of ONPs derived from a
patient diagnosed with schizophrenia (SZ) and an age- and gender-matched HCS.
Axonal formation was evidenced morphologically by tau immunostaining and by
GSK3beta phosphorylated state. Potassium-evoked secretion was assessed as a
functional feature of differentiated neurons. As well, we report the expression
of MT1/2 receptors in human ONPs for the first time. Melatonin stimulated axonal
formation and ramification in cloned ONPs through a receptor-mediated mechanism
and enhanced the amount and velocity of axonal and somatic secretion. SZ ONPs
displayed reduced axogenesis associated with lower levels of pGSK3beta and less
expression of melatonergic receptors regarding the HCS ONPs. Melatonin
counteracted this reduction in SZ cells. Altogether, our results show that
melatonin signaling is crucial for functional differentiation of human ONPs,
strongly suggesting that a deficit of this indoleamine may lead to an impaired
neurodevelopment which has been associated with the etiology of schizophrenia.
PMID- 28500771
TI - Large animal models of traumatic brain injury.
AB - Animal models are essential to gain a deeper understanding of the pathophysiology
associated with traumatic brain injury (TBI). Rodent models of TBI have proven
highly valuable with respect to the information they have provided over the
years, particularly when it comes to the molecular understanding of injury
mechanisms. However, there has been a failure to translate the successes in
therapeutic treatment of TBI in rodents, which many believe may be related to
their different brain anatomy compared with humans. Specifically, the rodent
lissencephalic brain within its bony skull responds differently to injury than a
human gyrencephalic brain, particularly from a biomechanical and physiological
perspective. There is now far greater interest in developing more clinically
relevant, large animal models of TBI so as to enhance the possibility of
successful clinical translation. The current mini-review highlights the
differences between lissencephalic and gyrencephalic brains, emphasizing how
these differences might impact studies of TBI. Thereafter follows a summary of
the different large animal models, with a critical analysis of their strengths
and weaknesses.
PMID- 28500772
TI - A test of genomic modularity among life-history adaptations promoting speciation
with gene flow.
AB - Speciation with gene flow may require adaptive divergence of multiple traits to
generate strong ecologically based reproductive isolation. Extensive negative
pleiotropy or physical linkage of genes in the wrong phase affecting these
diverging traits may therefore hinder speciation, while genetic independence or
"modularity" among phenotypic traits may reduce constraints and facilitate
divergence. Here, we test whether the genetics underlying two components of
diapause life history, initial diapause intensity and diapause termination
timing, constrain differentiation between sympatric hawthorn and apple-infesting
host races of the fly Rhagoletis pomonella through analysis of 10,256 SNPs
measured via genotyping-by-sequencing (GBS). Loci genetically associated with
diapause termination timing were mainly observed for SNPs mapping to chromosomes
1-3 in the genome, most notably for SNPs displaying higher levels of linkage
disequilibrium (LD), likely due to inversions. In contrast, selection on initial
diapause intensity affected loci on all five major chromosomes of the genome,
specifically those showing low levels of LD. This lack of overlap in genetically
associated loci suggests that the two diapause phenotypes are largely modular. On
chromosome 2, however, intermediate level LD loci and a subgroup of high LD loci
displayed significant negative relationships between initial diapause intensity
and diapause termination time. These gene regions on chromosome 2 therefore
affected both traits, while most regions were largely independent. Moreover, loci
associated with both measured traits also tended to exhibit highly divergent
allele frequencies between the host races. Thus, the presence of nonoverlapping
genetic modules likely facilitates simultaneous, adaptive divergence for the
measured life-history components.
PMID- 28500773
TI - The energy sensing LKB1-AMPKalpha1 pathway regulates IGF1 secretion and
consequent activation of the IGF1R-PKB pathway in primary hepatocytes.
AB - The insulin-like growth factor 1 (IGF1) pathway has been linked with various
diseases including diabetes, cancer and aging. In contrast to the well
established regulatory mechanisms controlling IGF1 expression, molecular
mechanisms regulating its secretion are not fully understood. The AMP-activated
protein kinase (AMPK) is a key energy sensor, and cumulative evidence shows that
it is an attractive therapeutic target for treatment of diabetes, cancer and
aging. Here we found that deficiency of AMPK promoted IGF1 secretion in mouse
primary hepatocytes. Furthermore, we found that AMPKalpha1 but not AMPKalpha2 was
involved in regulation of IGF1 secretion in mouse primary hepatocytes. Knockout
of AMPK caused activation of the IGF1 receptor (IGF1R)-protein kinase B (PKB;
also known as Akt) pathway in hepatocytes, which was mediated by hypersecretion
of IGF1. Upstream of AMPK, liver kinase B1 (LKB1) was responsible for AMPK
dependent suppression of IGF1 secretion in hepatocytes. Collectively, these
findings demonstrate that the energy-sensing LKB1-AMPK pathway regulates IGF1
secretion in mouse primary hepatocytes, which in turn regulates activation of the
IGF1R-PKB pathway.
PMID- 28500774
TI - The transcriptional landscape of seasonal coat colour moult in the snowshoe hare.
AB - Seasonal coat colour change is an important adaptation to seasonally changing
environments but the evolution of this and other circannual traits remains poorly
understood. In this study, we use gene expression to understand seasonal coat
colour moulting in wild snowshoe hares (Lepus americanus). We used hair colour to
follow the progression of the moult, simultaneously sampling skin from three
moulting stages in hares collected during the peak of the spring moult from white
winter to brown summer pelage. Using RNA sequencing, we tested whether patterns
of expression were consistent with predictions based on the established phases of
the hair growth cycle. We found functionally consistent clustering across skin
types, with 766 genes differentially expressed between moult stages. "White"
pelage showed more differentially expressed genes that were upregulated relative
to other skin types, involved in the transition between late telogen (quiescent
stage) and the onset of anagen (proliferative stage). Skin samples from
transitional "intermediate" and "brown" pelage were transcriptionally similar and
resembled the regressive transition to catagen (regressive stage). We also
detected differential expression of several key circadian clock and pigmentation
genes, providing important means to dissect the bases of alternate seasonal
colour morphs. Our results reveal that pelage colour is a useful biomarker for
seasonal change but that there is a consistent lag between the main gene
expression waves and change in visible coat colour. These experiments establish
that developmental sampling from natural populations of nonmodel organisms can
provide a crucial resource to dissect the genetic basis and evolution of complex
seasonally changing traits.
PMID- 28500775
TI - Vaccines against malaria-still a long way to go.
AB - Several species of Plasmodium cause a broad spectrum of human disease that range
from nausea and fever to severe anemia, cerebral malaria, and multiorgan failure.
In malaria-endemic countries, continuous exposure to Plasmodium sporozoite
inoculations and subsequent blood infections elicit only partial and short-lived
immunity, which gradually develops over many years of parasite exposure and
multiple clinical episodes. The ambitious goal of malaria vaccinology over the
past 70 years has been to develop an immunization strategy that mounts protection
superior to naturally acquired immunity. Herein, three principal concepts in
evidence-based malaria vaccine development are compared. Feasible leads are
typically stand-alone subunit vaccine approaches that block Plasmodium parasite
life cycle progression or parasite/host interactions, and they constitute the
majority of candidates in preclinical research and early clinical testing.
Integrated approaches incorporate malaria antigen(s) into licensed or emerging
pediatric vaccine formulations. This strategy can complement the malaria control
portfolio even if the antimalarial component is only partially effective and has
led to the development of the only candidate vaccine to date, namely RTS,S-AS01.
Experimental whole parasite vaccine approaches have been repeatedly shown to
elicit sterile and lasting protection against identical parasite strains, but
mass production, proof of broad protection against different parasite strains,
and routes of vaccine delivery remain significant translational road blocks.
Global access to an effective and affordable malaria vaccine will critically
depend on innovative translational research that builds on a better molecular
understanding of Plasmodium biology and host immunity.
PMID- 28500776
TI - Analysis of National Pharmacovigilance Data Associated with Statin Use in Korea.
AB - The aim of this study was to evaluate clinical manifestations, age distribution
and risk factors of adverse drug reactions (ADRs) of statins. Korean Adverse
Event Reporting System (KAERS) database records (July 2009-June 2014) on statin
treated adults were used. ADRs classified as 'certain', 'probable' and 'possible'
based on the WHO-Uppsala Monitoring Centre criteria were analysed. The frequency
of ADRs was compared between adults (18-64 years) and older people (age >=65
years) groups. In total, 2161 ADRs from 1690 patients (579, 34.3% older people)
were included for analysis. Mean patient age and ADRs per patient were 60.46 +/-
12.72 years and 1.28, respectively. ADRs were reported with atorvastatin (48.4%),
rosuvastatin (23.0%), pitavastatin (10.4%) and simvastatin (9.1%). The frequent
ADRs were gastrointestinal (421 events, 19.5%), musculoskeletal (331, 15.3%),
skin (312, 14.4%) and hepatobiliary disorders (286, 13.2%). Skin disorders were
significantly more frequent in adults compared to those in older patients (16.3%
versus 12.4%, p = 0.021). Common clinical symptoms were myalgia (263 events,
12.2%), dyspepsia (133, 6.2%) and pruritus (103, 4.8%). Myalgia was more
frequently reported in adults (12.7% versus 9.5%, p = 0.039) and dizziness was
more frequent in older people (3.4% versus 5.8%, p = 0.015). According to KAERS
data, leading statin ADRs were gastrointestinal and musculoskeletal disorders.
Myalgia and dyspepsia were the common clinical symptoms.
PMID- 28500777
TI - A comprehensive investigation of starch degradation process and identification of
a transcriptional activator MabHLH6 during banana fruit ripening.
AB - Although starch degradation has been well studied in model systems such as
Arabidopsis leaves and cereal seeds, this process in starchy fruits during
ripening, especially in bananas, is largely unknown. In this study, 38 genes
encoding starch degradation-related proteins were identified and characterized
from banana fruit. Expression analysis revealed that 27 candidate genes were
significantly induced during banana fruit ripening, with concomitant conversion
of starch-to-sugars. Furthermore, iTRAQ-based proteomics experiments identified
18 starch degradation-associated enzymes bound to the surface of starch granules,
of which 10 were markedly up-regulated during ripening. More importantly, a novel
bHLH transcription factor, MabHLH6, was identified based on a yeast one-hybrid
screening using MaGWD1 promoter as a bait. Transcript and protein levels of
MabHLH6 were also increased during fruit ripening. Electrophoretic mobility shift
assays, chromatin immunoprecipitation and transient expression experiments
confirmed that MabHLH6 activates the promoters of 11 starch degradation-related
genes, including MaGWD1, MaLSF2, MaBAM1, MaBAM2, MaBAM8, MaBAM10, MaAMY3,
MaAMY3C, MaISA2, MaISA3 and MapGlcT2-2 by recognizing their E-box (CANNTG) motifs
present in the promoters. Collectively, these findings suggest that starch
degradation during banana fruit ripening may be attributed to the complex actions
of numerous enzymes related to starch breakdown at transcriptional and
translational levels, and that MabHLH6 may act as a positive regulator of this
process via direct activation of a series of starch degradation-related genes.
PMID- 28500778
TI - Phaeohyphomycosis due to Exophiala infections in solid organ transplant
recipients: Case report and literature review.
AB - This case report and literature review underscores the cutaneous presentations of
phaeohyphomycosis in the solid organ transplant population. Increased cognizance
with prompt identification is critical. The therapy and clinical outcomes of
phaeohyphomycosis, caused by the Exophiala genus, in the solid organ transplant
population, is analyzed to examine optimal care. This review highlights the
inherent difficulties in providing the appropriate duration of antifungal therapy
to avoid relapsing infections in immunosuppressed patients.
PMID- 28500779
TI - Beyond nutrients: a meta-analysis of the diverse effects of arbuscular
mycorrhizal fungi on plants and soils.
AB - Arbuscular mycorrhizal fungi (AMF) can increase plant fitness under certain
environmental conditions. Among the mechanisms that may drive this mutualism, the
most studied is provisioning of nutrients by AMF in exchange for carbon from
plant hosts. However, AMF may also provide a suite of non-nutritional benefits to
plants including improved water uptake, disease resistance, plant chemical
defense, soil aggregation, and allelochemical transport and protection. Here, we
use a meta-analysis of 93 studies to assess the relative effect of AMF on
nutritional and non-nutritional factors that may influence plant fitness. We find
that the positive effects of AMF on soil aggregation, water flow and disease
resistance are equal to the effect of AMF on plant nitrogen and phosphorus
uptake. However, AMF had no effect on the uptake of other nutrients, plant water
content, allelopathic transport or production of chemical defense compounds. We
suggest future research directions, including experimentally assessing the
relative contribution on plant fitness of AMF interactions by untangling the
independence of alternative benefits of AMF from an increase in nutrient uptake.
This will lead to a more holistic view of the mycorrhizal-plant association and a
more accurate picture of the net impact on the plant or plant community in
question.
PMID- 28500780
TI - Prognostic factors of maternal near miss events and maternal deaths in a tertiary
healthcare facility in India.
AB - OBJECTIVE: To study maternal near miss (MNM) and maternal mortality to identify
rectifiable risk factors. METHODS: The present cross-sectional retrospective
study included pregnant women who experienced acute life-threatening pregnancy
related adverse events at Deen Dayal Upadhyay hospital, New Delhi, India, between
September 1, 2009, and August 31, 2011. Patient data were analyzed to investigate
factors associated with MNM events and maternal deaths. RESULTS: There were 369
patients included, and 302 MNM events and 67 maternal deaths were recorded. The
recorded causes of MNM events included hemorrhage, hypertensive disorders, severe
anemia with cardiac failure, organ failure, and infection in 192 (63.6%), 62
(20.5%), 13 (4.3%), 8 (2.6%), and 8 (2.6%) patients, respectively. Higher rates
of anemia (P=0.007) and infection (P=0.007) were recorded among patients in the
maternal death group than the MNMN group. CONCLUSION: Hemorrhage and hypertension
were major causes of MNM events and are likely major barriers to reducing
maternal mortality in low-income countries. Anemia and infection were significant
prognostic factors of maternal death in the present study. MNM could be used as
surrogate for maternal death in the provision of standard obstetric care.
PMID- 28500781
TI - Pregnancy outcomes in simultaneous pancreas and kidney transplant recipients: a
national French survey study.
AB - Simultaneous pancreas and kidney transplantation (SPK) is currently the best
therapeutic option for patients with type 1 diabetes and terminal renal failure.
Renal transplantation restores fertility enabling women to pursue pregnancies.
However, scarcity of available data on pregnancy outcomes in SPK impedes fair
medical counseling. Medical files of all pregnancies that lasted >=3 months among
recipients of functional SPK performed between 1990 and 2015 in France were
retrospectively analyzed. Twenty-six pregnancies in 22 SPK recipients were
identified. Main maternal complications included gestational hypertension (53.8%)
and infections (50%). Cesarean section was performed in 73% of cases. Overall
fetal survival was 92.6% with a mean gestational age of 34.2 +/- 3 weeks. Four
children (16.7% of live births) had a birth weight <10th percentile. Endocrine
pancreas graft function remained stable during pregnancy. An acute kidney
rejection occurred in two patients, one of which resulting in graft loss. Kidney
and pancreas graft survival was, respectively, 96% and 100% at 1 year
postconception and did not differ from controls. Pregnancy in SPK is feasible,
but patients should be informed of the risks for the fetus, the mother, and the
grafts. Planning of pregnancy in SPK women is key to allow a personalized
multidisciplinary monitoring, which represents the most straightforward approach
to optimize outcomes.
PMID- 28500783
TI - On mixed electron-photon radiation therapy optimization using the column
generation approach.
AB - PURPOSE: Despite considerable increase in the number of degrees of freedom
handled by recent radiotherapy optimisation algorithms, treatments are still
typically delivered using a single modality. Column generation is an iterative
method for solving large optimisation problems. It is well suited for mixed
modality (e.g., photon-electron) optimisation as the aperture shaping and
modality selection problem can be solved rapidly, and the performance of the
algorithm scales favourably with increasing degrees of freedom. We demonstrate
that the column generation method applied to mixed photon-electron planning can
efficiently generate treatment plans and investigate its behaviour under
different aperture addition schemes. MATERIALS AND METHODS: Column generation was
applied to the problem of mixed-modality treatment planning for a chest wall case
and a leg sarcoma case. 6 MV beamlets (100 cm SAD) were generated for the photon
components along with 5 energies for electron beamlets (6, 9, 12, 16 and 20 MeV),
simulated as shortened-SAD (80 cm) beams collimated with a photon MLC. For the
chest wall case, IMRT-only, modulated electron radiation therapy (MERT)-only, and
mixed electron-photon (MBRT) treatment plans were created using the same planning
criteria. For the sarcoma case, MBRT and MERT plans were created to study the
behaviour of the algorithm under two different sets of planning criteria designed
to favour specific modalities. Finally, the efficiency and plan quality of four
different aperture addition schemes was analysed by creating chest wall MBRT
treatment plans which incorporate more than a single aperture per iteration of
the column generation loop based on a heuristic aperture ranking scheme. RESULTS:
MBRT plans produced superior target coverage and homogeneity relative to IMRT and
MERT plans created using the same optimisation criteria, all the while preserving
the normal tissue-sparing advantages of electron therapy. Adjusting the planning
criteria to favour a specific modality in the sarcoma case resulted in the
algorithm correctly emphasizing the appropriate modality. As expected, adding a
single aperture per iteration yielded the lowest (best) cost function value per
aperture included in the treatment plan. However, a greedier scheme was able to
converge to approximately the same cost function after 125 apertures in one third
of the running time. Electron apertures were on average 50-100% larger than
photon apertures for all aperture addition schemes. The distribution of
intensities among the available modalities followed a similar trend for all
schemes, with the dominant modalities being 6 MV photons along with 6, 9 and 20
MeV electrons. CONCLUSION: The column generation method applied to mixed modality
treatment planning was able to produce clinically realistic treatment plans and
combined the advantages of photon and electron radiotherapy. The running time of
the algorithm depended heavily on the choice of mixing scheme. Adding the highest
ranked aperture for each modality provided the best trade-off between running
time and plan quality for a fixed number of apertures. This work contributes an
efficient methodology for the planning of mixed electron-photon treatments.
PMID- 28500782
TI - Melatonin protects bone marrow mesenchymal stem cells against iron overload
induced aberrant differentiation and senescence.
AB - Bone marrow mesenchymal stem cells (BMSCs) are an expandable population of stem
cells which can differentiate into osteoblasts, chondrocytes and adipocytes.
Dysfunction of BMSCs in response to pathological stimuli contributes to bone
diseases. Melatonin, a hormone secreted from pineal gland, has been proved to be
an important mediator in bone formation and mineralization. The aim of this study
was to investigate whether melatonin protected against iron overload-induced
dysfunction of BMSCs and its underlying mechanisms. Here, we found that iron
overload induced by ferric ammonium citrate (FAC) caused irregularly
morphological changes and markedly reduced the viability in BMSCs. Consistently,
osteogenic differentiation of BMSCs was significantly inhibited by iron overload,
but melatonin treatment rescued osteogenic differentiation of BMSCs. Furthermore,
exposure to FAC led to the senescence in BMSCs, which was attenuated by melatonin
as well. Meanwhile, melatonin was able to counter the reduction in cell
proliferation by iron overload in BMSCs. In addition, protective effects of
melatonin on iron overload-induced dysfunction of BMSCs were abolished by its
inhibitor luzindole. Also, melatonin protected BMSCs against iron overload
induced ROS accumulation and membrane potential depolarization. Further study
uncovered that melatonin inhibited the upregulation of p53, ERK and p38 protein
expressions in BMSCs with iron overload. Collectively, melatonin plays a
protective role in iron overload-induced osteogenic differentiation dysfunction
and senescence through blocking ROS accumulation and p53/ERK/p38 activation.
PMID- 28500784
TI - Nonablative fractional laser-assisted daylight photodynamic therapy with topical
methyl aminolevulinate for moderate to severe facial acne vulgaris: Results of a
randomized and comparative study.
AB - BACKGROUND: Photodynamic therapy (PDT) has been reported as an effective
alternative treatment for patients with acne. PURPOSE: To evaluate the efficacy
and safety of DL-PDT in moderate to severe acne and to compare outcomes with
those of laser-assisted daylight photodynamic therapy. METHODS: Patients were
randomly assigned to either a DL-PDT group (D group) or a fractional laser
assisted DL-PDT group (F group). The outcomes were assessed by measuring acne
lesion counts and severity grade at 4, 8, 12, and 16 weeks after therapy
commenced. RESULTS: Twenty-eight subjects completed the study. Compared with
baseline, the mean inflammatory lesion counts significantly decreased by 36.0% in
the D group and 51.8% in the F group at 8 weeks (P<.001). The mean acne severity
grades in both groups significantly decreased starting at 4 weeks (P=.012), and
the beneficial effects lasted 16 weeks. CONCLUSION: DL-PDT with MAL shows
clinically good responses to inflammatory lesions and is well tolerated in
patients with moderate to severe acne.
PMID- 28500785
TI - Don't Label Me: A Qualitative Study of Patients' Perceptions and Experiences of
Sedation During Behavioral Emergencies in the Emergency Department.
AB - OBJECTIVES: Behavioral emergencies are commonly seen in emergency departments
(EDs). Acutely agitated patients can be difficult to manage and sedation may be
required to decrease dangerous behavior and to ensure the safety of both the
patient and the staff. While the experience of staff caring for this population
has been reported, patients' experiences with their overall management remains
unknown. We aimed to describe the perceptions and experiences of patients
regarding the use of sedation during acute behavioral emergencies. METHODS: Face
to-face semistructured interviews were conducted with adults aged 18 years or
older, who had received parenteral sedative medication for the management of a
behavioral emergency and were deemed capable to participate. The participants
were asked about their experiences of receiving care in the ED during the episode
and their perceptions of sedation. All interviews were transcribed verbatim and
analyzed thematically. RESULTS: Data saturation was reached after 13 interviews.
Two broad themes emerged: trusting relationships and needs or wants following
sedation. A trusting relationship is built through 1) confidence in care, 2)
sedation as an appropriate treatment, 3) insight into own behavior, and 4) humane
treatment. Four subthemes of needs or wants were identified: 1) empathy, 2)
debrief, 3) addressing concerns, and 4) follow-up. CONCLUSIONS: A trusting
relationship was identified as crucial to minimize the negative impact of
coercive measures used to manage behavioral emergencies. Participants expressed
similar needs to patients presenting with medical problems. This study
illustrates their needs for compassionate communication, adequate information
about the treatment provided, and follow-up care.
PMID- 28500786
TI - Dovitinib enhances temozolomide efficacy in glioblastoma cells.
AB - The multikinase inhibitor and FDA-approved drug dovitinib (Dov) crosses the blood
brain barrier and was recently used as single drug application in clinical trials
for GB patients with recurrent disease. The Dov-mediated molecular mechanisms in
GB cells are unknown. We used GB patient cells and cell lines to show that Dov
downregulated the stem cell protein Lin28 and its target high-mobility group
protein A2 (HMGA2). The Dov-induced reduction in pSTAT3Tyr705 phosphorylation
demonstrated that Dov negatively affects the STAT3/LIN28/Let-7/HMGA2 regulatory
axis in GB cells. Consistent with the known function of LIN28 and HMGA2 in GB
self-renewal, Dov reduced GB tumor sphere formation. Dov treatment also caused
the downregulation of key base excision repair factors and O6 -methylguanine-DNA
methyltransferase (MGMT), which are known to have important roles in the repair
of temozolomide (TMZ)-induced alkylating DNA damage. Combined Dov/TMZ treatment
enhanced TMZ-induced DNA damage as quantified by nuclear gammaH2AX foci and comet
assays, and increased GB cell apoptosis. Pretreatment of GB cells with Dov ('Dov
priming') prior to TMZ treatment reduced GB cell viability independent of p53
status. Sequential treatment involving 'Dov priming' and alternating treatment
cycles with TMZ and Dov substantially reduced long-term GB cell survival in MGMT+
patient GB cells. Our results may have immediate clinical implications to improve
TMZ response in patients with LIN28+ /HMGA2+ GB, independent of their MGMT
methylation status.
PMID- 28500787
TI - Corticosterone primes the neuroinflammatory response to Gulf War Illness-relevant
organophosphates independently of acetylcholinesterase inhibition.
AB - Gulf War Illness (GWI) is a chronic multi-symptom disorder affecting veterans of
the 1991 Gulf War. Among the symptoms of GWI are those associated with sickness
behavior, observations suggestive of underlying neuroinflammation. We have shown
that exposure of mice to the stress hormone, corticosterone (CORT), and to
diisopropyl fluorophosphate (DFP), as a nerve agent mimic, results in marked
neuroinflammation, findings consistent with a stress/neuroimmune basis of GWI.
Here, we examined the contribution of irreversible and reversible
acetylcholinesterase (AChE) inhibitors to neuroinflammation in our mouse model of
GWI. Male C57BL/6J mice received 4 days of CORT (400 mg/L) in the drinking water
followed by a single dose of chlorpyrifos oxon (CPO; 8 mg/kg, i.p.), DFP (4
mg/kg, i.p.), pyridostigmine bromide (PB; 3 mg/kg, i.p.), or physostigmine (PHY;
0.5 mg/kg, i.p.). CPO and DFP alone caused cortical and hippocampal
neuroinflammation assessed by qPCR of tumor necrosis factor-alpha, IL-6, C-C
chemokine ligand 2, IL-1beta, leukemia inhibitory factor and oncostatin M; CORT
pretreatment markedly augmented these effects. Additionally, CORT exposure prior
to DFP or CPO enhanced activation of the neuroinflammation signal transducer,
signal transducer and activator of transcription 3 (STAT3). In contrast, PHY or
PB alone or with CORT pretreatment did not produce neuroinflammation or STAT3
activation. While all of the CNS-acting AChE inhibitors (DFP, CPO, and PHY)
decreased brain AChE activity, CORT pretreatment abrogated these effects for the
irreversible inhibitors. Taken together, these findings suggest that irreversible
AChE inhibitor-induced neuroinflammation and particularly its exacerbation by
CORT, result from non-cholinergic effects of these compounds, pointing
potentially to organophosphorylation of other neuroimmune targets.
PMID- 28500788
TI - Unraveling the importance of the malaria parasite helicases.
AB - Malaria is a human parasitic disease caused by infection from Plasmodium species,
particularly Plasmodium falciparum. Each year millions of people are infected
with malaria and large numbers of deaths result due to this deadly infection. P.
falciparum contains 14 chromosomes, nearly 5400 genes and a multistage life cycle
in humans and mosquitoes. The control of malaria is still a challenge as the
parasite is continuously developing resistance to available antimalarial drugs
and the mosquito vector is developing resistance to insecticides. The
availability of P. falciparum genome has resulted in the identification of
parasite-specific proteins that can be targeted without harmful effects to the
human host. Toward this goal, we have been working on the identification and
characterization of helicases in order to find parasite-specific helicases, which
can be used as novel drug targets to tackle the rising problem of drug
resistance. Helicases are ATP-dependent nucleic acid unwinding enzymes. The P.
falciparum genome analysis depicts that it contains some parasite-specific
helicases and homologs to most of the human helicases. Here, we present an
overview of P. falciparum helicases and their importance in parasite growth and
survival.
PMID- 28500789
TI - Atlantic small-mammal: a dataset of communities of rodents and marsupials of the
Atlantic forests of South America.
AB - The contribution of small mammal ecology to the understanding of macroecological
patterns of biodiversity, population dynamics, and community assembly has been
hindered by the absence of large datasets of small mammal communities from
tropical regions. Here we compile the largest dataset of inventories of small
mammal communities for the Neotropical region. The dataset reviews small mammal
communities from the Atlantic forest of South America, one of the regions with
the highest diversity of small mammals and a global biodiversity hotspot, though
currently covering less than 12% of its original area due to anthropogenic
pressures. The dataset comprises 136 references from 300 locations covering seven
vegetation types of tropical and subtropical Atlantic forests of South America,
and presents data on species composition, richness, and relative abundance
(captures/trap-nights). One paper was published more than 70 yr ago, but 80% of
them were published after 2000. The dataset comprises 53,518 individuals of 124
species of small mammals, including 30 species of marsupials and 94 species of
rodents. Species richness averaged 8.2 species (1-21) per site. Only two species
occurred in more than 50% of the sites (the common opossum, Didelphis aurita and
black-footed pigmy rice rat Oligoryzomys nigripes). Mean species abundance varied
430-fold, from 4.3 to 0.01 individuals/trap-night. The dataset also revealed a
hyper-dominance of 22 species that comprised 78.29% of all individuals captured,
with only seven species representing 44% of all captures. The information
contained on this dataset can be applied in the study of macroecological patterns
of biodiversity, communities, and populations, but also to evaluate the
ecological consequences of fragmentation and defaunation, and predict disease
outbreaks, trophic interactions and community dynamics in this biodiversity
hotspot.
PMID- 28500790
TI - Accuracy evaluation of a six-degree-of-freedom couch using cone beam CT and
IsoCal phantom with an in-house algorithm.
AB - PURPOSE: The accuracy of a six degree of freedom (6DoF) couch was evaluated using
a novel method. METHODS: Cone beam CT (CBCT) images of a 3D phantom (IsoCal) were
acquired with different, known combinations of couch pitch and roll angles. Pitch
and roll angles between the maximum allowable values of 357 and 3 degrees were
tested in one degree increments. A total of 49 combinations were tested at 0
degrees of yaw (couch rotation angle). The 3D positions of 16 tungsten carbide
ball bearings (BBs), each 4 mm in diameter and arranged in a known geometry
within the IsoCal phantom, were determined in the 49 image sets with in-house
software. The BB positions at different rotation angles were determined using a
rotation matrix from the original BB positions at zero pitch and roll angles. A
linear least squares fit method estimated the rotation angles and differences
between detected and nominal rotation angles were calculated. This study was
conducted for the case with and without extra weight on the couch. Couch walk
shifts for the system were investigated using eight combinations of rotation,
roll and pitch. RESULTS: A total of 49 CBCT images with voxel sizes 0.5 * 0.5 *
1.0 mm3 were taken for the case without extra weight on the couch. The 16 BBs
were determined to evaluate the isocenter translation and rotation differences
between the calculated and nominal couch values. Among all 49 calculations, the
maximum rotation angle differences were 0.10 degrees for pitch, 0.15 degrees for
roll and 0.09 degrees for yaw. The corresponding mean and standard deviation
values were 0.028 +/- 0.032, -0.043 +/- 0.058, and -0.009 +/- 0.033 degrees. The
maximum translation differences were 0.3 mm in the left-right direction, 0.5 mm
in the anterior-posterior direction and 0.4 mm in the superior-inferior
direction. The mean values and corresponding standard deviations were 0.07 +/-
0.12, -0.05 +/- 0.25, and -0.12+/-0.14 mm for the planes described above. With an
80 kg phantom on the couch, the maximum translation shift was 0.69 mm. The couch
walk translation shifts were less than 0.1 mm and rotation shifts were less than
0.1 degree. CONCLUSIONS: Errors of a new 6DoF couch were tested using CBCT images
of a 3D phantom. The rotation errors were less than 0.3 degree and the
translation errors were less than or equal to 0.8 mm in each direction. This
level of accuracy is warranted for clinical radiotherapy utilization including
stereotactic radiosurgery.
PMID- 28500791
TI - Fire catalyzed rapid ecological change in lowland coniferous forests of the
Pacific Northwest over the past 14,000 years.
AB - Disturbance can catalyze rapid ecological change by causing widespread mortality
and initiating successional pathways, and during times of climate change,
disturbance may contribute to ecosystem state changes by initiating a new
successional pathway. In the Pacific Northwest of North America (PNW),
disturbance by wildfires strongly shapes the composition and structure of lowland
forests, but understanding the role of fire over periods of climate change is
challenging, because fire-return intervals are long (e.g., millennia) and the
coniferous trees dominating these forests can live for many centuries. We
developed stand-scale paleorecords of vegetation and fire that span nearly the
past 14,000 yr to study how fire was associated with state changes and rapid
dynamics in forest vegetation at the stand scale (1-3 ha). We studied forest
history with sediment cores from small hollow sites in the Marckworth State
Forest, located ~1 km apart in the Tsuga heterophylla Zone in the Puget Lowland
ecoregion of western Washington, USA. The median rate of change in pollen/spore
assemblages was similar between sites (0.12 and 0.14% per year), but at both
sites, rates of change increased significantly following fire events (ranging up
to 1% per year, with a median of 0.28 and 0.38%, P < 0.003). During times of low
climate velocity, forest composition was resilient to fires, which initiated
successional pathways leading back to the dominant vegetation type. In contrast,
during times of high climate variability and velocity (e.g., the early Holocene)
forests were not resilient to fires, which triggered large-scale state changes.
These records provide clear evidence that disturbance, in the form of an
individual fire event, can be an important catalyst for rapid state changes,
accelerating vegetation shifts in response to large-scale climate change.
PMID- 28500792
TI - Changing trends in the aetiology, treatment and outcomes of bloodstream infection
occurring in the first year after solid organ transplantation: a single-centre
prospective cohort study.
AB - To analyse trends in the aetiology, treatment and outcomes of bloodstream
infection (BSI) within the first year post-transplant over the last 10-year
period, we prospectively recorded all episodes of BSI occurring in solid organ
transplant (SOT) recipients during the first year post-transplant from 2007 to
2016. Trends of factors were analysed by 2-year periods. Of 475 consecutive
episodes of BSI, 218 occurred within a year of SOT in 178 SOT recipients. Gram
positive BSI decreased over time (40.5-2.2%). In contrast, there was a steady
increase in Gram-negative bacilli (GNB) BSI (54.1-93.3%; P < 0.001), mainly due
to Pseudomonas aeruginosa (2.4-20.4%) and Klebsiella pneumoniae (7.1-26.5%).
Multidrug-resistant (MDR) GNB (4.8-38.8%; P < 0.001) rose dramatically,
especially due to extended-spectrum beta-lactamase (ESBL) production (7.1-34.7%).
There was a sharp rise in the use of carbapenems, both as empirical (11.9-55.3%;
P < 0.001) and as targeted antibiotic treatment (11.9-46.9%; P < 0.001). In
conclusion, today, GNB are the leading causative agents of BSI in SOT recipients
within the first year after SOT. In addition, MDR GNB have emerged mainly due to
ESBL-producing strains. In spite of these changes, length of hospital stay, days
of treatment and mortality have remained stable over time.
PMID- 28500793
TI - Integrating the genomic architecture of human nucleolar organizer regions with
the biophysical properties of nucleoli.
AB - Nucleoli are the sites of ribosome biogenesis and the largest membraneless
subnuclear structures. They are intimately linked with growth and proliferation
control and function as sensors of cellular stress. Nucleoli form around arrays
of ribosomal gene (rDNA) repeats also called nucleolar organizer regions (NORs).
In humans, NORs are located on the short arms of all five human acrocentric
chromosomes. Multiple NORs contribute to the formation of large heterochromatin
surrounded nucleoli observed in most human cells. Here we will review recent
findings about their genomic architecture. The dynamic nature of nucleoli began
to be appreciated with the advent of photodynamic experiments using fluorescent
protein fusions. We review more recent data on nucleoli in Xenopus germinal
vesicles (GVs) which has revealed a liquid droplet-like behavior that facilitates
nucleolar fusion. Further analysis in both XenopusGVs and Drosophila embryos
indicates that the internal organization of nucleoli is generated by a
combination of liquid-liquid phase separation and active processes involving
rDNA. We will attempt to integrate these recent findings with the genomic
architecture of human NORs to advance our understanding of how nucleoli form and
respond to stress in human cells.
PMID- 28500794
TI - Rapid, broad-scale gene expression evolution in experimentally harvested fish
populations.
AB - Gene expression changes potentially play an important role in adaptive evolution
under human-induced selection pressures, but this has been challenging to
demonstrate in natural populations. Fishing exhibits strong selection pressure
against large body size, thus potentially inducing evolutionary changes in life
history and other traits that may be slowly reversible once fishing ceases.
However, there is a lack of convincing examples regarding the speed and magnitude
of fisheries-induced evolution, and thus, the relevant underlying molecular-level
effects remain elusive. We use wild-origin zebrafish (Danio rerio) as a model for
harvest-induced evolution. We experimentally demonstrate broad-scale gene
expression changes induced by just five generations of size-selective harvesting,
and limited genetic convergence following the cessation of harvesting. We also
demonstrate significant allele frequency changes in genes that were
differentially expressed after five generations of size-selective harvesting. We
further show that nine generations of captive breeding induced substantial gene
expression changes in control stocks likely due to inadvertent selection in the
captive environment. The large extent and rapid pace of the gene expression
changes caused by both harvest-induced selection and captive breeding emphasizes
the need for evolutionary enlightened management towards sustainable fisheries.
PMID- 28500795
TI - The future distribution of river fish: The complex interplay of climate and land
use changes, species dispersal and movement barriers.
AB - The future distribution of river fishes will be jointly affected by climate and
land use changes forcing species to move in space. However, little is known
whether fish species will be able to keep pace with predicted climate and land
use-driven habitat shifts, in particular in fragmented river networks. In this
study, we coupled species distribution models (stepwise boosted regression trees)
of 17 fish species with species-specific models of their dispersal (fish
dispersal model FIDIMO) in the European River Elbe catchment. We quantified (i)
the extent and direction (up- vs. downstream) of predicted habitat shifts under
coupled "moderate" and "severe" climate and land use change scenarios for 2050,
and (ii) the dispersal abilities of fishes to track predicted habitat shifts
while explicitly considering movement barriers (e.g., weirs, dams). Our results
revealed median net losses of suitable habitats of 24 and 94 river kilometers per
species for the moderate and severe future scenarios, respectively. Predicted
habitat gains and losses and the direction of habitat shifts were highly variable
among species. Habitat gains were negatively related to fish body size, i.e.,
suitable habitats were projected to expand for smaller-bodied fishes and to
contract for larger-bodied fishes. Moreover, habitats of lowland fish species
were predicted to shift downstream, whereas those of headwater species showed
upstream shifts. The dispersal model indicated that suitable habitats are likely
to shift faster than species might disperse. In particular, smaller-bodied fish
(<200 mm) seem most vulnerable and least able to track future environmental
change as their habitat shifted most and they are typically weaker dispersers.
Furthermore, fishes and particularly larger-bodied species might substantially be
restricted by movement barriers to respond to predicted climate and land use
changes, while smaller-bodied species are rather restricted by their specific
dispersal ability.
PMID- 28500796
TI - High-density genotyping of the A.E. Watkins Collection of hexaploid landraces
identifies a large molecular diversity compared to elite bread wheat.
AB - The importance of wheat as a food crop makes it a major target for agricultural
improvements. As one of the most widely grown cereal grains, together with maize
and rice, wheat is the leading provider of calories in the global diet,
constituting 29% of global cereal production in 2015. In the last few decades,
however, yields have plateaued, suggesting that the green revolution, at least
for wheat, might have run its course and that new sources of genetic variation
are urgently required. The overall aim of our work was to identify novel
variation that may then be used to enable the breeding process. As landraces are
a potential source of such diversity, here we have characterized the A.E. Watkins
Collection alongside a collection of elite accessions using two complementary
high-density and high-throughput genotyping platforms. While our results show the
importance of using the appropriate SNP collection to compare diverse accessions,
they also show that the Watkins Collection contains a substantial amount of novel
genetic diversity which has either not been captured in current breeding
programmes or which has been lost through previous selection pressures. As a
consequence of our analysis, we have identified a number of accessions which
carry an array of novel alleles along with a number of interesting chromosome
rearrangements which confirm the variable nature of the wheat genome.
PMID- 28500798
TI - Persistent Sick Sinus Syndrome in Scrub Typhus.
PMID- 28500797
TI - Fatal Flea-Borne Typhus in Texas: A Retrospective Case Series, 1985-2015.
AB - AbstractFlea-borne (murine) typhus is a global rickettsiosis caused by Rickettsia
typhi. Although flea-borne typhus is no longer nationally notifiable, cases are
reported for surveillance purposes in a few U.S. states. The infection is
typically self-limiting, but may be severe or life-threatening in some patients.
We performed a retrospective review of confirmed or probable cases of fatal flea
borne typhus reported to the Texas Department of State Health Services during
1985-2015. When available, medical charts were also examined. Eleven cases of
fatal flea-borne typhus were identified. The median patient age was 62 years
(range, 36-84 years) and 8 (73%) were male. Patients presented most commonly with
fever (100%), nausea and vomiting (55%), and rash (55%). Respiratory (55%) and
neurologic (45%) manifestations were also identified frequently. Laboratory
abnormalities included thrombocytopenia (82%) and elevated hepatic transaminases
(63%). Flea or animal contact before illness onset was frequently reported (55%).
The median time from hospitalization to administration of a tetracycline-class
drug was 4 days (range, 0-5 days). The median time from symptom onset to death
was 14 days (range, 1-34 days). Flea-borne typhus can be a life-threatening
disease if not treated in a timely manner with appropriate tetracycline-class
antibiotics. Flea-borne typhus should be considered in febrile patients with
animal or flea exposure and respiratory or neurologic symptoms of unknown
etiology.
PMID- 28500799
TI - Erratum.
PMID- 28500800
TI - First Insight Into the Fluoroquinolone and Aminoglycoside Resistance of Multidrug
Resistant Mycobacterium tuberculosis in Saudi Arabia.
AB - AbstractIn Saudi Arabia, there were no nationwide screening studies conducted so
far to determine the aminoglycoside and fluoroquinolone resistance among
multidrug-resistant tuberculosis (MDR-TB) isolates. Therefore, as the first
attempt in the country, a retrospective analysis has been conducted on a
nationwide collection of 2,956 M. tuberculosis clinical isolates screened with
phenotypic drug susceptibility testing to define MDR-TB. Enrolled MDR-TB isolates
were subjected to second-line drug susceptibility testing, detection of mutations
conferring resistance to aminoglycosides and fluoroquinolone, followed by 24-loci
mycobacterial interspersed repetitive unit-variable number of tandem repeat
typing and spoligotyping. Overall, 83 isolates were identified as MDR-TB, and 13
(15.7%) isolates showed resistance to second-line drugs. Moxifloxacin (low level)
showed higher resistant rates (10.8%) followed by ofloxacin (7.2%), capreomycin
(3.6%), kanamycin (3.6%), and amikacin (2.4%). Overall fluoroquinolone resistance
was 12%, whereas aminoglycoside resistance was 7.2%. Predominant mutations
conferring resistance to fluoroquinolone were found in gyrA A90V and D94G,
whereas aminoglycoside resistance was observed only with rrs gene A1401G
mutation. The corresponding strain lineages predominated with Indo-Oceanic and
East-African Indian origin. Interestingly, none of the isolates with second-line
drug resistance was defined as extensively drug-resistant TB (XDR-TB).
Surprisingly, many isolates (50.6%) were panresistant to first-line drugs. Saudi
Arabia faces considerable burden of fluoroquinolone- and aminoglycoside-resistant
MDR-TB. Higher incidence of panresistant MDR-TB reveals a threat for the
emergence of XDR-TB strains in the near future.
PMID- 28500801
TI - A Malaria-Resistant Phenotype with Immunological Correlates in a Tanzanian Birth
Cohort Exposed to Intense Malaria Transmission.
AB - AbstractMalaria incidence is highly heterogeneous even in areas of high
transmission, although no conclusive evidence exists that innate or naturally
acquired resistance can prevent infection over an extended period of time. This
longitudinal study examined immunoparasitological evidence for a malaria
resistant phenotype in which children do not develop malaria despite an extended
period of exposure to parasites. Within a birth cohort followed from 2002 to 2006
in Muheza, Tanzania, an area of intense transmission, children (N = 687) provided
blood smears biweekly during infancy and monthly thereafter. Maternal and
childhood characteristics were obtained, cord-blood cytokines were measured, and
antibody responses were assayed as measures of stage-specific exposure. Sixty
three (9.2%) children had no blood smear-positive slides over 2 years of follow
up (range: 1-3.5 years) and were identified as malaria resistant. Malaria
resistant children were similar to other children with respect to completeness of
follow-up and all maternal and childhood characteristics except residence area.
Antibody seroprevalence was similar for two sporozoite antigens, but malaria
resistant children had a lower antibody seroprevalence to merozoite antigens
merozoite surface protein 1 (5.4% versus 30.2%; P < 0.0001) and apical membrane
antigen 1 (7.2% versus 33.3%; P < 0.0001). Malaria-resistant children had higher
cytokine levels in cord blood, particularly interleukin-1beta. In summary, a
subset of children living in an area of intense transmission was exposed to
malaria parasites, but never developed patent parasitemia; this phenotype was
associated with a distinct cytokine profile at birth and antibody profile during
infancy. Further research with malaria-resistant children may identify mechanisms
for naturally acquired immunity.
PMID- 28500802
TI - High-Resolution Melting Curve Analysis of the 16S Ribosomal Gene to Detect and
Identify Pathogenic and Saprophytic Leptospira Species in Colombian Isolates.
AB - AbstractIt is important to identify the circulating Leptospira agent to enhance
the performance of serodiagnostic tests by incorporating specific antigens of
native species, develop vaccines that take into account the species/serovars
circulating in different regions, and optimize prevention and control strategies.
The objectives of this study were to develop a polymerase chain reaction (PCR)
high-resolution melting (HRM) assay for differentiating between species of the
genus Leptospira and to verify its usefulness in identifying unknown samples to
species level. A set of primers from the initial region of the 16S ribosomal gene
was designed to detect and differentiate the 22 species of Leptospira. Eleven
reference strains were used as controls to establish the reference species and
differential melting curves. Twenty-five Colombian Leptospira isolates were
studied to evaluate the usefulness of the PCR-HRM assay in identifying unknown
samples to species level. This identification was confirmed by sequencing and
phylogenetic analysis of the 16S ribosomal gene. Eleven Leptospira species were
successfully identified, except for Leptospira meyeri/Leptospira yanagawae
because the sequences were 100% identical. The 25 isolates from humans, animals,
and environmental water sources were identified as Leptospira santarosai
(twelve), Leptospira interrogans (nine), and L. meyeri/L. yanagawae (four). The
species verification was 100% concordant between PCR-HRM and phylogenetic
analysis of the 16S ribosomal gene. The PCR-HRM assay designed in this study is a
useful tool for identifying Leptospira species from isolates.
PMID- 28500803
TI - Patients' Delay in Seeking Health Care for Tuberculosis Diagnosis in East Gojjam
Zone, Northwest Ethiopia.
AB - AbstractPatients' delay in seeking diagnosis is a major problem in the management
of tuberculosis (TB). Relative to the burden of TB, there is lack of data on the
magnitude of delays in seeking care and why patients fail to seek early care at
health facilities in Ethiopia. A facility-based cross-sectional study was
conducted from April to July 2013 in East Gojjam Zone, Amhara, Ethiopia, to
assess patients' delays and associated factors in TB patients. Using simple
random sampling, 605 (327 male and 278 female) participants were recruited. Of
the total, 323 (53.4%) TB patients were delayed in seeking health care (median =
45 days; mean = 78.5 days). The following independent variables were associated
with patient delays: age >= 45 years (adjusted odds ratio [AOR] = 8.74, 95%
confidence interval [CI] = 4.71-16.23, P < 0.001); working as a farmer (AOR =
4.18, 95% CI = 1.44-12.11, P = 0.009); prior visit to holy water sites,
traditional healers, and/or private drug shops (AOR = 69.11, 95% CI =13.91
343.29, P < 0.001; AOR = 14.74, 95% CI = 1.43-152.31, P = 0.024; AOR = 2.10, 95%
CI = 1.22-3.59, P = 0.007, respectively); poor knowledge about TB (AOR = 2.79,
95% CI = 1.74-4.92, P = 0.006), and extrapulmonary TB (AOR = 14.69, 95% CI = 8.21
26.26, P < 0.001). Generally, patients' delay in seeking care at health
facilities was high (53.4%). Most of TB patients getting treatment from holy
water (95.3%; 101/106) and traditional healers (84.6%; 11/13) were delayed.
Therefore, for early seeking in modern health care, a combination of
interventions is required to encourage TB patients.
PMID- 28500804
TI - A Large Outbreak of Thiamine Deficiency Among Illegal Gold Miners in French
Guiana.
AB - From September 2013 to July 2014, several gold miners working in the tropical
forest consulted the Maripasoula Health Center in French Guiana for edema and
findings consistent with right-sided cardiac failure. Of the 42 cases of beriberi
that were diagnosed, one patient died. The laboratory and clinical investigation
demonstrated vitamin B1 deficiency in most of the patients tested. Furthermore,
30 of 42 patients responded favorably to 500 mg of intravenous or intramuscular
thiamine supplementation. In addition, dietary investigation showed insufficient
thiamine intake in these patients. We concluded that patients had acquired
beriberi because of diet restrictions, hard labor, and infectious diseases,
notably malaria. In 2016, cases were still being reported. We recommend screening
for compatible symptoms in gold miners, thiamine supplementation, and nutritional
intervention.
PMID- 28500805
TI - Unusual Otolaryngologic Manifestations of Paracoccidioidomycosis: A Case Report
and Review of Literature.
AB - AbstractParacoccidioidomycosis is a systemic mycosis caused by Paracoccidioides
brasiliensis. It occurs more frequently in its chronic form, which particularly
affects male adults from rural areas. These patients present with pulmonary
involvement and systemic symptoms. Skin and mucosal lesions are rather typical
and might suggest the diagnosis. The involvement of the upper airway mucosa is
common and the patients usually complain of dysphagia and dysphonia. Nonetheless,
in endemic areas, physicians should maintain a high level of suspicion even when
faced with some atypical symptoms. We present the case of an adult diagnosed with
nasopharyngeal paracoccidioidomycosis after presenting with an unusual
otolaryngologic syndrome including unilateral soft palate paralysis with
velopharyngeal insufficiency and hearing loss secondary to middle ear effusion.
PMID- 28500807
TI - The Eyes Have It-Or Do They?
PMID- 28500808
TI - Seroprevalence of Scrub Typhus, Typhus, and Spotted Fever Among Rural and Urban
Populations of Northern Vietnam.
AB - AbstractRickettsial infections are recognized as important causes of fever
throughout southeast Asia. Herein, we determined the seroprevalence to
rickettsioses within rural and urban populations of northern Vietnam. Prevalence
of individuals with evidence of prior rickettsial infections (IgG positive) was
surprisingly low, with 9.14% (83/908) testing positive to the three major
rickettsial serogroups thought to circulate in the region. Prevalence of typhus
group rickettsiae (TG)-specific antibodies (6.5%, 58/908) was significantly
greater than scrub typhus group orientiae (STG)- or spotted fever group
rickettsiae (SFG)-specific antibodies (P < 0.05). The majority of TG
seropositives were observed among urban rather than rural residents (P < 0.05).
In contrast, overall antibody prevalence to STG and SFG were both very low (1.1%,
10/908 for STG; 1.7%, 15/908 for SFG), with no significant differences between
rural and urban residents. These results provide data on baseline population
characteristics that may help inform development of Rickettsia serological
testing criteria in future clinical studies.
PMID- 28500809
TI - Investigating Mumps Outbreak in Odisha, India: An Opportunity to Assess the
Health System by Utilizing the Essential Public Health Services Framework.
AB - AbstractMumps, a highly contagious, viral disease continues to spread in India,
despite the availability of an effective vaccine. On November 24, 2014, we came
across a suspected case of mumps in a 6-year-old boy in a village of Bhusandapur
sector in Odisha. We initiated an outbreak investigation using standard
techniques outlined by the Centers for Disease Control and Prevention, Atlanta,
GA. This uncovered a silent epidemic of 94 case patients (10% of the population)
over a period of 16 weeks between August and December 2014, in a single village,
which had gone completely unnoticed by the existing health-care system. Since the
index case was one of the last case patients of the outbreak, investigation for
immediate control was not a priority. Hence, we have used this exercise to
describe the outbreak and identify causes that led to its nondetection. Age range
of the case patients was between 2 and 40 years; 85 (90.4%) case patients were <=
15 years of age and 54 (57.4%) were females. Average duration of illness was 9
days. No child had received the mumps vaccine. The outbreak had led to a
community expenditure of 538 USD. The exercise uncovered a number of weak links
in the essential public health services within the health-care delivery system in
the area.
PMID- 28500806
TI - Antibody Responses to Plasmodium falciparum and Plasmodium vivax and Prospective
Risk of Plasmodium spp. Infection Postpartum.
AB - AbstractPostpartum women may have an altered susceptibility to Plasmodium
falciparum and Plasmodium vivax. The relationship between naturally acquired
malarial immunity and susceptibility to malaria postpartum is yet to be
determined. IgG levels were measured against P. falciparum and P. vivax antigens
from delivery in 201 postpartum and 201 nonpregnant controls over 12 weeks.
Associations between time-varying antibody levels and time to first
microscopically confirmed species-specific infection were determined by Cox
regression. Associations between antibody levels and prospective risk of
Plasmodium infection were similar in postpartum and control women. A 2-fold
increase in P. falciparum antibody levels was associated with increased
prospective risk of P. falciparum infection (hazard ratio [HR] range = 1.37
1.94). Antibody levels against most P. vivax antigens displayed no association
with prospective risk of P. vivax infection (HR range = 1.02-1.05) with the
exception of PvMSP119 antibodies that were weakly associated with prospective
risk of P. vivax infection (HR = 1.14 (95% confidence interval = 1.02, 1.28) per
2-fold increase in levels). Associations between antibody levels and prospective
risk of infection attenuated when adjusted for documented retrospective exposure.
Serology may be a useful tool to predict and monitor women at increased risk of
P. falciparum infection postpartum, particularly in the absence of a detailed
history of retrospective infections.
PMID- 28500810
TI - Environmental and Behavioral Drivers of Buruli Ulcer Disease in Selected
Communities Along the Densu River Basin of Ghana: A Case-Control Study.
AB - AbstractThe exact route of transmission of Mycobacterium ulcerans (MU) (causative
agent of Buruli ulcer [BU]), risk factors, and reservoir hosts are not clearly
known, although it has been identified as an environmental pathogen. This study
assessed potential environmental and behavioral risk factors that influence BU
infections. We conducted a case-control study where cases were matched by their
demographic characteristics and place of residence. A structured questionnaire
was administered to solicit information on the environmental and behavioral
factors of participants that may expose them to infection. A total of 176 cases
and 176 controls were enrolled into the study. Multivariate conditional logistic
regression analysis identified farming in swampy areas (odds ratio [OR] = 4.10,
95% confidence interval [CI] = 3.82-7.18), farming while wearing short clothing
(OR = 1,734.1, 95% CI = 68.1-44,120.9), insect bite (OR = 988.3, 95% CI = 31.4
31,115.6), and application of leaves on wounds (OR = 6.23, 95% CI = 4.74-18.11)
as potential risk factors. Farming in long clothing (OR = 0.000, 95% CI = 0.00
0.14), washing wound with water and soap (OR = 0.37, 95% CI = 0.29-0.98), and
application of adhesive bandage on wounds (OR = 0.31, 95% CI = 0.15-0.82) were
found to be protective against BU infection. In the absence of the exact MU
transmission mechanisms, education of public in BU-endemic zones on the use of
protective clothing during farming activities to limit exposure of the skin and
proper wound care management would be essential in the fight against BU.
PMID- 28500812
TI - The Prevalence of Chagas Disease Among Latin American Immigrants with Pacemakers
in Los Angeles, California.
AB - AbstractChagas disease (CD), with associated conduction abnormalities, is a
common indication for pacemaker implantation in Latin America. The prevalence of
CD in Latin American immigrants with pacemakers residing in the United States has
never been studied. This single-center cross-sectional study included pacemaker
patients who were aged 18 years or more with a previous residence in Latin
America for at least 6 months. Patients with an implantable cardioverter
defibrillator, cardiac resynchronization therapy, or iatrogenic and/or congenital
heart block were excluded. Serological testing for Trypanosoma cruzi was
performed at enrollment. A total of 80 patients were enrolled, and CD was
diagnosed in six patients (7.5%). Patients with CD were more likely to be from El
Salvador (P = 0.001). Other clinical, therapeutic, electrocardiographic, and
echocardiographic variables were similar between the CD and non-CD groups. There
is a high prevalence of CD among Latin American immigrants with pacemakers in Los
Angeles.
PMID- 28500811
TI - Cost-Effectiveness of Dengue Vaccination Programs in Brazil.
AB - AbstractThe first approved dengue vaccine, CYD-TDV, a chimeric, live-attenuated,
tetravalent dengue virus vaccine, was recently licensed in 13 countries,
including Brazil. In light of recent vaccine approval, we modeled the cost
effectiveness of potential vaccination policies mathematically based on data from
recent vaccine efficacy trials that indicated that vaccine efficacy was lower in
seronegative individuals than in seropositive individuals. In our analysis, we
investigated several vaccination programs, including routine vaccination, with
various vaccine coverage levels and those with and without large catch-up
campaigns. As it is unclear whether the vaccine protects against infection or
just against disease, our model incorporated both direct and indirect effects of
vaccination. We found that in the presence of vaccine-induced indirect
protection, the cost-effectiveness of dengue vaccination decreased with
increasing vaccine coverage levels because the marginal returns of herd immunity
decreases with vaccine coverage. All routine dengue vaccination programs that we
considered were cost-effective, reducing dengue incidence significantly.
Specifically, a routine dengue vaccination of 9-year-olds would be cost-effective
when the cost of vaccination per individual is less than $262. Furthermore, the
combination of routine vaccination and large catch-up campaigns resulted in a
greater reduction of dengue burden (by up to 93%) than routine vaccination alone,
making it a cost-effective intervention as long as the cost per course of
vaccination is $255 or less. Our results show that dengue vaccination would be
cost-effective in Brazil even with a relatively low vaccine efficacy in
seronegative individuals.
PMID- 28500813
TI - Quality of Case Management for Pneumonia and Diarrhea Among Children Seen at
Health Facilities in Southern Malawi.
AB - Pneumonia and diarrhea are leading causes of child deaths in Malawi. Guidelines
to manage childhood illnesses in resource-poor settings exist, but studies have
reported low health-care worker (HCW) adherence to guidelines. We conducted a
health facility survey from January to March 2015 to assess HCW management of
pneumonia and diarrhea in children < 5 years of age in southern Malawi, and to
determine factors associated with case management quality. Descriptive statistics
and multivariable logistic regression models examined patient, HCW, and health
facility factors associated with recommended pneumonia and diarrhea management,
using Malawi's national guidelines as the gold standard. Of 694 surveyed children
2-59 months of age at 95 health facilities, 132 (19.0%) met survey criteria for
pneumonia; HCWs gave recommended antibiotic treatment to 90 (68.2%). Of 723
children < 5 years of age, 222 (30.7%) had uncomplicated diarrhea; HCWs provided
recommended treatment to 94 (42.3%). In multivariable analyses, caregivers'
spontaneous report of children's symptoms was associated with recommended
treatment of both pneumonia (odds ratio [OR]: 2.8, 95% confidence interval [CI]:
1.2-6.8, P = 0.023) and diarrhea (OR: 24.2, 95% CI: 6.0-97.0, P < 0001). Malaria
diagnosis was negatively associated with recommended treatment (OR for pneumonia:
0.5, 95% CI: 0.2-1.0, P = 0.046; OR for diarrhea: 0.3, 95% CI: 0.1-0.6, P =
0.003). To improve quality of care, children should be assessed systematically,
even when malaria is suspected. Renewed efforts to invigorate such a systematic
approach, including HCW training, regular follow-up supervision, and monitoring
HCW performance, are needed in Malawi.
PMID- 28500814
TI - FTA Cards Facilitate Storage, Shipment, and Detection of Arboviruses in Infected
Aedes aegypti Collected in Adult Mosquito Traps.
AB - AbstractThe utility of applying infected Aedes aegypti to Flinders Technology
Associates (FTA(r)) cards for storage, transport, and detection of dengue, Zika,
and Barmah Forest viruses was assessed in laboratory-based experiments. The
mosquitoes had been removed from Gravid Aedes Traps maintained under conditions
of high temperature and humidity. RNA of all viruses could be detected in
infected mosquitoes on FTA cards either individually or in pools with uninfected
mosquitoes, and stored for up to 28 days. Importantly, there was only a minimal
decrease in RNA levels in mosquitoes between days 0 and 28, indicating that viral
RNA was relatively stable on the cards. FTA cards thus provide a mechanism for
storing potentially infected mosquitoes collected in the field and transporting
them to a central diagnostic facility for virus detection.
PMID- 28500815
TI - Oral Pentoxifylline Associated with Pentavalent Antimony: A Randomized Trial for
Cutaneous Leishmaniasis.
AB - AbstractCutaneous leishmaniasis (CL) by Leishmania braziliensis is associated
with decreasing cure rates in Brazil. Standard treatment with pentavalent
antimony (Sbv) cures only 50-60% of the cases. The immunopathogenesis of CL ulcer
is associated with high interferon-gamma and tumor necrosis factor (TNF)
production. Pentoxifylline, a TNF inhibitor, has been successfully used in
association with Sbv in mucosal and cutaneous leishmaniasis. This randomized,
double-blind, and placebo-controlled trial aimed to evaluate the efficacy and
safety of oral pentoxifylline plus Sbv versus placebo plus Sbv in patients with
CL in Bahia, Brazil. A total of 164 patients were randomized in two groups to
receive the combination or the monotherapy. Cure rate 6 months after treatment
was 45% in the pentoxifylline group and 43% in the control group. There was also
no difference between the groups regarding the healing time (99.7 +/- 66.2 days
and 98.1 +/- 72.7 days, respectively). Adverse events were more common in the
pentoxifylline group (37.8%), versus 23% in the placebo group. This trial shows
that Sbv combined therapy with pentoxifylline is not more effective than Sbv
monotherapy in the treatment of CL caused by L. braziliensis.
PMID- 28500817
TI - Transmission Incompetence of Culex quinquefasciatus and Culex pipiens pipiens
from North America for Zika Virus.
AB - AbstractIn late 2014, Zika virus (ZIKV; Flaviviridae, Flavivirus) emerged as a
significant arboviral disease threat in the Western hemisphere. Aedes aegypti and
Aedes albopictus have been considered the principal vectors of ZIKV in the New
World due to viral isolation frequency and vector competence assessments. Limited
reports of Culex transmission potential have highlighted the need for additional
vector competence assessments of North American Culex species. Accordingly, North
American Culex pipiens and Culex quinquefasciatus were orally exposed and
intrathoracically inoculated with the African prototype ZIKV strain and currently
circulating Asian lineage ZIKV strains to assess infection, dissemination, and
transmission potential. Results indicated that these two North American Culex
mosquito species were highly refractory to oral infection with no dissemination
or transmission observed with any ZIKV strains assessed. Furthermore, both Culex
mosquito species intrathoracically inoculated with either Asian or African
lineage ZIKVs failed to expectorate virus in saliva. These in vivo results were
further supported by the observation that multiple mosquito cell lines of Culex
species origin demonstrated significant growth restriction of ZIKV strains
compared with Aedes-derived cell lines. In summation, no evidence for the
potential of Cx. pipiens or Cx. quinquefasciatus to serve as a competent vector
for ZIKV transmission in North America was observed.
PMID- 28500819
TI - Primary Pancreatic Hydatid: A Rare Cystic Lesion of the Pancreas.
PMID- 28500816
TI - Serum Lipids and Lipoproteins During Uncomplicated Malaria: A Cohort Study in
Lambarene, Gabon.
AB - AbstractThe serum lipid profile in malaria patients has been found to differ from
that of healthy controls. We investigated serum lipid profile changes in malaria
patients over time compared with patients with other febrile diseases. In total,
217 patients were included in the study (111 malaria patients and 106 symptomatic
controls, defined as malaria-negative febrile patients). Serum lipid levels
(mmol/L) were significantly lower in malaria patients compared with those with
other febrile diseases (total cholesterol [TC] = 3.26 [standard deviation = 0.94]
versus 3.97 [1.22; P < 0.001]; high-density lipoprotein cholesterol [HDL-C] =
0.43 [0.47] versus 1.05 [0.67; P < 0.001], low-density lipoprotein cholesterol
[LDL-C] = 2.05 [0.76] versus 2.42 [0.90; P < 0.001]. Triglycerides (TGs) levels
were higher in malaria patients (1.81 [1.02] versus 1.11 [0.82; P < 0.001]). No
significant differences were found for apolipoprotein A1, apolipoprotein B, and
lipoprotein(a). Cholesterol levels increased toward reference values on day 28
(TC = 3.26-3.98, P < 0.001; HDL-C = 0.43-0.96, P < 0.001; LDL-C = 2.05-2.60, P <
0.001). TG levels decreased from 1.81 on admission to 1.76 (day 3) and 0.88 (day
28; P = 0.130). Lipid profile changes were not correlated with parasitemia or
Plasmodium falciparum histidine-rich protein 2 levels. This study confirms
characteristic temporary lipid profile changes in malaria. Lipid profile changes
demonstrated a good accuracy to discriminate between malaria and other febrile
diseases (area under the curve = 0.80 (95% confidence interval = 0.742-0.863, P <
0.001). Several plausible hypotheses exist regarding the pathophysiology of lipid
profile changes in malaria. Further studies to elucidate the precise pathways may
lead to improved understanding of the underlying pathophysiology.
PMID- 28500818
TI - Household Microbial Water Quality Testing in a Peruvian Demographic and Health
Survey: Evaluation of the Compartment Bag Test for Escherichia coli.
AB - AbstractThe Joint Monitoring Program relies on household surveys to classify
access to improved water sources instead of measuring microbiological quality.
The aim of this research was to pilot a novel test for Escherichia coli
quantification of household drinking water in the 2011 Demographic and Health
Survey (DHS) in Peru. In the Compartment Bag Test (CBT), a 100-mL water sample is
supplemented with chromogenic medium to support the growth of E. coli, poured
into a bag with compartments, and incubated. A color change indicates E. coli
growth, and the concentration of E. coli/100 mL is estimated as a most probable
number. Triplicate water samples from 704 households were collected; one sample
was analyzed in the field using the CBT, another replicate sample using the CBT
was analyzed by reference laboratories, and one sample using membrane filtration
(MF) was analyzed by reference laboratories. There were no statistically
significant differences in E. coli concentrations between the field and
laboratory CBT results, or when compared with MF results. These results suggest
that the CBT for E. coli is an effective method to quantify fecal bacteria in
household drinking water. The CBT can be incorporated into DHS and other national
household surveys as a direct measure of drinking water safety based on microbial
quality to better document access to safe drinking water.
PMID- 28500820
TI - Jared Diamond Confidential Reflections on Writing, Science, and Life.
PMID- 28500822
TI - Erratum.
PMID- 28500821
TI - Serum Carbonic Anhydrase 1 is a Biomarker for Diagnosis of Human Schistosoma
mansoni Infection.
AB - AbstractSchistosoma mansoni is a major public health threat in many parts of the
world. The current diagnostic tests for schistosomiasis are suboptimal,
particularly early in infection, when the parasite burden is low and with
reinfection after treatment. We sought to identify novel biomarkers of active
infection by studying serum proteins in a mouse model of schistosomiasis followed
by confirmation in chronically infected patients. Acute (6 weeks) and chronic (12
weeks) sera from S. mansoni-infected C57Bl/6 mice as well as sera from
chronically infected patients were assessed using two proteomic platforms:
surface-enhanced, laser desorption and ionization, time-of-flight mass
spectrometry and Velos Orbitrap mass spectrometry. Several candidate biomarkers
were further evaluated by Western blot and/or enzyme-linked immunosorbent assay
(ELISA). Among the most promising was carbonic anhydrase 1 (CA1), a host protein
found primarily in red blood cells and enterocytes that proved to be a negative
biomarker for schistosomiasis in both mouse and human samples. Reduced serum CA-1
levels were confirmed by both Western blot (murine and human: both P < 0.001) and
ELISA (human: P < 0.01). Western blots of serial mouse sera revealed a
progressive reduction in serum CA1 levels over the 12-week infection period. CA1
is a promising negative serum biomarker for the diagnosis of S. mansoni
infection.
PMID- 28500824
TI - Vitamin D and aspects of female fertility.
AB - The role of vitamin D in female reproduction has been intensively examined over
the last few decades. A large body of evidence suggests that vitamin D might have
beneficial effects on metabolic/hormonal parameters of PCOS and endometriosis,
while it appears to be associated with IVF outcomes. However, due to the
heterogeneity among observational and interventional studies, no cause-effect
relationship has yet been established. The aim of this review is to analyze
recent in vitro animal and human studies which examined the association of
vitamin D with disease entities affecting female fertility potential. Recent
research data strongly imply that vitamin D is implicated in female reproduction
and might represent a beneficial and inexpensive therapeutic approach, in
combination with first-line medical treatments, to female infertility.
PMID- 28500823
TI - Aflatoxin Exposure During Pregnancy, Maternal Anemia, and Adverse Birth Outcomes.
AB - AbstractPregnant women and their developing fetuses are vulnerable to multiple
environmental insults, including exposure to aflatoxin, a mycotoxin that may
contaminate as much as 25% of the world food supply. We reviewed and integrated
findings from studies of aflatoxin exposure during pregnancy and evaluated
potential links to adverse pregnancy outcomes. We identified 27 studies (10 human
cross-sectional studies and 17 animal studies) assessing the relationship between
aflatoxin exposure and adverse birth outcomes or anemia. Findings suggest that
aflatoxin exposure during pregnancy may impair fetal growth. Only one human study
investigated aflatoxin exposure and prematurity, and no studies investigated its
relationship with pregnancy loss, but animal studies suggest aflatoxin exposure
may increase risk for prematurity and pregnancy loss. The fetus could be affected
by maternal aflatoxin exposure through direct toxicity as well as indirect
toxicity, via maternal systemic inflammation, impaired placental growth, or
elevation of placental cytokines. The cytotoxic and systemic effects of aflatoxin
could plausibly mediate maternal anemia, intrauterine growth restriction, fetal
loss, and preterm birth. Given the widespread exposure to this toxin in
developing countries, longitudinal studies in pregnant women are needed to
provide stronger evidence for the role of aflatoxin in adverse pregnancy
outcomes, and to explore biological mechanisms. Potential pathways for
intervention to reduce aflatoxin exposure are urgently needed, and this might
reduce the global burden of stillbirth, preterm birth, and low birthweight.
PMID- 28500825
TI - Which type 2 diabetes mellitus patients should be screened for subclinical
Cushing's syndrome?
AB - OBJECTIVE: Diabetes or impaired glucose tolerance are common in patients with
Cushing's syndrome (CS). In this study we investigated the incidence of
subclinical Cushing's syndrome (SCS) in type 2 diabetic patients with poor and
good metabolic control and the relationship between blood glucose and cortisol
levels. DESIGN: A total of 400 type 2 diabetes mellitus (T2DM) patients (Group A,
HbA1c >=8%, n=250; Group B, HbA1c <=6.5%, n=150) were included in the study.
Biochemical tests followed by the 1 mg dexamethasone suppression test (DST) were
performed. If post-DST cortisol levels were above 1.8 MUg/dl (non-suppressed
group), the 2 mg DST test was performed for 2 days. Among the patients, post-DST
cortisol of at least 1.8 MUg/dL and midnight serum cortisol levels of at least
7.5 MUg/dL confirmed the diagnosis of CS. RESULTS: While SCS was observed in 5
patients (2%) in Group A, no case was observed in group B. There was a
statistically significant difference between groups for basal cortisol and post
DST cortisol results (p<0.001 and p<0.001, respectively). Microvascular
complication rates were higher in the non-suppressed group (p=0.007). Post-DST
cortisol levels had a positive correlation with the number of complications and
HbA1c levels (respectively r=0.213, p<0.001, and r=0.191, p<0.001). Multivariate
regression analysis revealed that durations of DM, HbA1c level, and post 1 mg DST
cortisol levels were associated with the number of complications. CONCLUSIONS:
This study shows the presence of SCS in a notable number in T2DM patients having
poor metabolic control. Screening with 1 mg and 2 mg DST of T2DM patients with
poor metabolic control who are also obese and hypertensive and have microvascular
complications may be an appropriate method for detection of SCS.
PMID- 28500826
TI - Serum kisspeptin concentrations are negatively correlated with body mass index in
adolescents with anorexia nervosa and amenorrhea.
AB - OBJECTIVE: To measure, for the first time, serum kisspeptin concentrations in
adolescent females with anorexia nervosa (AN) and associated amenorrhea, and
investigate potential correlations of kisspeptin with anthropometric, bone and
hormonal data. DESIGN: Setting: University Adolescent Medicine Center.
PARTICIPANTS: Females aged 12-20 years with typical or atypical AN (based on DSM
5 diagnostic criteria) and controls. INTERVENTIONS: Measurement of body mass
index (BMI), whole body/lumbar spine bone mineral density and serum
concentrations of kisspeptin, follicle stimulating hormone, luteinizing hormone
(LH), prolactin (PRL), thyroid stimulating hormone (TSH), free thyroxine,
triiodothyronine, estradiol (E2), 17-hydroxyprogesterone. MAIN OUTCOME MEASURES:
Kisspeptin serum concentrations and correlations between kisspeptin and AN
related anthropometric, bone and hormonal changes. RESULTS: Participants included
37 females, 22 with AN (typical AN group=17, atypical AN group=5) and 15 in the
control group. All typical AN patients had secondary amenorrhea. Wide inter
subject variation (101.9-709.1 ng/L) in kisspeptin levels was observed with no
significant differences among study groups; there was a trend toward higher
concentrations in the atypical AN group. Adolescents with typical AN had
significantly lower BMI (P<0.001), lumbar spine z-score (P=0.016), serum E2
(P<0.001), LH (P=0.016), PRL (P=0.034) and TSH (P=0.045) than controls. They also
had lower BMI (P=0.009) and TSH (P=0.027) than girls with atypical AN. An inverse
correlation between BMI and serum kisspeptin was noted in the typical AN group
(r=-0.60, P=0.012). CONCLUSIONS: Serum kisspeptin concentrations overlapped
between patients and controls; in typical anorexic adolescents kisspeptin
concentrations were negatively correlated with BMI. Future studies are needed to
explore kisspeptin physiology in AN.
PMID- 28500827
TI - Psychological vulnerability to stress in carriers of congenital adrenal
hyperplasia due to 21-hydroxylase deficiency.
AB - OBJECTIVE: Carriers of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase
deficiency (21-OHD) demonstrate increased secretion of cortisol precursors
following ACTH stimulation, suggestive of impaired cortisol production and
compensatory increases in hypothalamic corticotropin-releasing hormone (CRH)
secretion. Both cortisol and CRH have behavioral effects, and hypothalamic CRH
hypersecretion has been associated with chronic states of anxiety and depression.
We performed an endocrinologic and psychological evaluation in carriers of 21-OHD
and matched control subjects. DESIGN: We recruited 29 parents of children with
classic CAH (14 males, 15 females; age (mean+/-SD): 41.8+/-5.7 yr), and hence 21
OHD carriers, and 13 normal subjects (5 males, 8 females; age: 43.8+/-6.1 yr).
All subjects underwent a formal ovine (o) CRH stimulation test with measurement
of ACTH, cortisol, 17-hydroxyprogesterone (17-OHP) and androstenedione
concentrations, which was preceded by determination of 24-hour urinary free
cortisol (UFC) excretion. Psychometric assessment was performed by administering
the State-Anxiety (STAI 1) and Trait-Anxiety (STAI 2) Inventory, Beck Depression
Inventory, Symptom Checklist-90R and Temperament and Character Inventory.
RESULTS: Carriers of 21-OHD had significantly higher 17-OHP concentrations
following oCRH stimulation and higher STAI 1 (47.6+/-5.6 vs. 43.3+/-5.4, P=0.023)
scores than control subjects. Mean 24-hour UFC concentrations were positively
correlated with paranoid ideation (r=0.435; P=0.023) and psychoticism (r=0.454;
P=0.017). Stepwise multiple linear regression analysis revealed that the single
independent predictor of STAI 1 was peak stimulated 17-OHP concentrations (beta:
0.055, SE: 0.023, R2: 0.290, P=0.031). CONCLUSIONS: Carriers of 21-OHD may be
predisposed to the development of anxiety disorders.
PMID- 28500828
TI - The impact of thyroid autoimmunity (TPOAb) on bone density and fracture risk in
postmenopausal women.
AB - OBJECTIVE: Skeletal development, linear growth, cartilage biology and bone
turnover are highly dependent on the activity of thyroid hormones. Thyroid
dysfunction affects the skeleton, and autoimmune thyroid disease, manifesting as
a chronic inflammatory condition, may be an important contributing factor to
impaired bone quality in these patients. MATERIALS AND METHODS: Measurement of
TSH, FT4, TPOAb and bone mineral density and FRAX score calculations were
performed in 189 postmenopausal women (110 euthyroid women and 79 women diagnosed
with subclinical hypothyroidism) divided into subgroups according to the presence
of TPOAb. RESULTS: In multivariate logistic regression analysis only TPOAb were
found to be significantly related to fracture, independently of TSH values
(p=0.018; OR=7.800; 95% CI 1.424-42.721). Lower bone mineral density and FRAX
score for hip and for major osteoporotic fractures were associated with the
presence of TPOAb in euthyroid postmenopausal women in an unadjusted logistic
regression model, as well as in a model adjusted for age, BMI and smoking. TSH
was a better predictive factor for fractures in women with subclinical
hypothyroidism (FRAX main p <0.001; 95% CI for SE 0.858-0.959 and FRAX hip p
<0.001; 95% CI for SE 0.628-0.854). CONCLUSION: Autoimmune thyroid disease is
associated with decreased bone mineral density at both spine and hip and risk of
future fracture incidence in euthyroid postmenopausal women. Presence of TPOAb is
a potential marker of higher fracture risk in these patients. However, in
subclinical hypothyroidism, TSH is a better indicator of future fragility
fractures than TPOAb.
PMID- 28500829
TI - Removal of a high-fat diet, but not voluntary exercise, reverses obesity and
diabetic-like symptoms in male C57BL/6J mice.
AB - OBJECTIVE: Both the consumption of high-fat diets and exercise are known to
produce alterations in metabolism and behavior. This study focuses on the effects
of a change to a low-fat diet from a high-fat diet and voluntary exercise on
obesity, type-2 diabetic-like symptoms, and locomotor behavior in male C57BL/6J
mice. DESIGN: Mice were initially given either a high-fat diet or regular chow,
along with a cage with a running-wheel to mimic exercise, or one without, to
determine to what extend exercise affects these symptoms. Then half of the mice
given a high-fat diet were switched to regular chow to ascertain if the switch in
diet would improve type-2 diabetic-like and obesity symptoms. RESULTS: Wheel
running alone produced an improvement in insulin in mice continuously fed a high
fat diet (p=0.006), but running-wheels did not produce any further improvements
in mice with regular chow replacement (p=0.999) or in controls (p=0.996).
Replacement of a high-fat diet with regular chow led to physiological
improvements in insulin (p=0.012) and leptin (p <0.001), glucose tolerance (p
<0.001), and obesity (p <0.001), more so than exercise alone. Mice consuming a
high-fat diet without a wheel exhibited reduced home-cage activity compared to
controls after the diet switch (p=0.030), while no reduction was found in running
wheel activity between high-fat diet and regular chow consuming mice after
switching diets (p=0.516). CONCLUSIONS: These results suggest that exercise is
only partially beneficial to improving health outcomes in mice consuming a high
fat diet, whereas incorporating a better diet, even without exercise, improves
quality of health and can suppress T2DM symptoms and related conditions more so
than exercise alone.
PMID- 28500830
TI - Association between TPO Asn698Thr and Thr725Pro gene polymorphisms and serum anti
TPO levels in Iranian patients with subclinical hypothyroidism.
AB - OBJECTIVE: Subclinical hypothyroidism (SCH) is defined as high levels of TSH in
the presence of normal levels of serum FT4. Since thyroid peroxidase (TPO) plays
a key role in thyroid hormone synthesis, variations in the TPO gene can change
the enzyme structure and result in the production of anti-TPO antibodies. The aim
of this study was to examine the relationship between the Asn698Thr (A2095C) and
Thr725Pro (A2173C) polymorphisms of the TPO gene and anti-TPO levels in patients
with SCH. DESIGN: In this study, 150 individuals (75 cases and 75 controls), aged
19-75 years, were selected randomly by a clinician. The thyroid function tests
included were FT3, FT4, TSH and anti-TPO antibodies using ELISA. The TPO gene
polymorphisms were examined by PCR-RFLP. RESULTS: Anti-TPO levels in the
experimental group was significantly increased (P=0.020). The A2095C genotype
frequency in the experimental and control groups were 37.3% vs 34.7% for the AA
healthy genotype, 20% vs 46.7% for AC and 42.7% vs 18.6% for CC, respectively
(P=0.001). The A2173C genotype frequency in the experimental and control groups
were 22.6% vs 68% for healthy AA, 40% vs 25.3% for AC and 37.4% vs 6.7% for CC,
respectively (P <0.001). The increased anti-TPO antibodies were significantly
associated with the A2173C polymorphism (P=0.035). The findings showed that the
chance (odds ratio) of developing subclinical hypothyroidism in individuals who
had C alleles was 1.5 and 5.6-fold higher than in individuals without these
alleles in the A2095C and A2173C regions, respectively. CONCLUSIONS:
Determination of anti-TPO antibody levels and exon 12 TPO gene polymorphisms in
patients with SCH can be helpful for prediction of overt hypothyroidism.
PMID- 28500831
TI - Somatotropinomas inadequately controlled with octreotide may over-respond to
pasireotide: the importance of dose adjustment to achieve long-term biochemical
control.
AB - OBJECTIVE: To present two female patients with acromegaly inadequately controlled
with long-acting octreotide who were subsequently treated with the multireceptor
targeted somatostatin analogue pasireotide that over-suppressed IGF-1 levels.
METHODS: We report two patients who failed surgery and received long-acting
octreotide 20-30 mg/month as part of two double-blind, Phase III clinical trials.
After 6-12 months of octreotide treatment, both patients remained inadequately
controlled and were switched to long-acting pasireotide 40 mg/month as part of a
crossover extension phase. RESULTS: During the core phase of the studies the
patients received octreotide 20-30 mg/month, but GH and IGF-1 levels remained
above normal. They were switched to pasireotide 40 mg/month after 6 and 12
months, according to the study protocols. After crossover, GH and IGF-1 decreased
and normalized, but continued treatment led to further reduction of IGF-1 to
below the normal; these reduced levels mildly increased following pasireotide
dose reduction to 20 mg/month. Tumour volume was reduced and the clinical signs
and symptoms of acromegaly also improved. CONCLUSION: These patients achieved
long-term biochemical control, tumour volume reduction and improvement of
clinical signs/symptoms after switching from octreotide to pasireotide. IGF-1
over-suppression is observed in a few patients and requires dose adjustment of
pasireotide.
PMID- 28500832
TI - Combined pituitary hormone deficiency in a girl with 48, XXXX and Rathke's cleft
cyst.
AB - BACKGROUND: Tetrasomy X is a rare chromosomal aneuploidy seen in girls,
associated with facial dysmorphism, premature ovarian insufficiency and
intellectual disability. A Rathke's cleft cyst (RCC) is a remnant of Rathke's
pouch which may cause multiple pituitary hormone deficiencies by exerting
pressure on the pituitary gland in the sella. METHODS/RESULTS: The patient was
diagnosed with tetrasomy X by karyotyping during infancy. Brain MRI and multiple
endocrine stimulation tests revealed RCC and combined pituitary hormone
deficiency (growth hormone deficiency, secondary adrenal insufficiency and
central hypothyroidism) likely due to RCC. CONCLUSION: We report the first case
in the literature of a girl with 48, XXXX and combined pituitary hormone
deficiency due to Rathke's cyst.
PMID- 28500833
TI - The male bride: a story of Sexual Female-to-Male Transformation at marriage from
the Hellenistic period, recorded by Phlegon of Tralles.
PMID- 28500834
TI - Hermaphroditism: an obsolete diagnosis?
PMID- 28500835
TI - Hypophysis. From outgrowth, to ocular disorder to pituitary gland.
PMID- 28500856
TI - Effect of low-level laser therapy on tissue repair after dental extraction in
rats administered zoledronic acid and dexamethasone.
AB - Bisphosphonates (BPs) are being increasingly used for the treatment of metabolic
and oncological pathologies involving the skeletal system. Because of the
severity of the BP associated osteonecrosis of the jaws, the difficulties of
treatment, and patient discomfort, additional support methods for their
management are needed. Laser therapy has an easy handling, photobiostimulator
effect on tissues healing, so it can be considered a preferred therapy. The aim
of this study was to evaluate the influence of low-level laser therapy in the 685
and 830-nm wavelength in the healing process of the bone and soft tissues in
rats under BP therapy [zoledronic acid (ZA)] and dexamethasone concomitantly that
underwent a surgery for the extraction of upper molars. There were statistically
significant differences in the clinical evaluation of the wound and the weight of
the animals. Regarding the histological evaluation, it was possible to observe
the different maturations of the healing stage between groups. The effect of drug
therapy with ZA and dexamethasone in the bone tissue repair process induces
osteonecrosis of the jaw in rats and slows down the healing process. In the laser
groups, at the stipulated dosimetry, a positive influence on the bone and soft
tissue repair process was observed.
PMID- 28500855
TI - The Evolutionary Theory of Depression.
AB - The evolutionary success of Homo sapiens is attributed to the following two
factors: the upright body posture (which freed our hands and allowed
unconstrained operation of various objects) and intensive development of the
frontal lobes, mainly the Broca area of the brain. Underlining the uniqueness of
the human brain, we often forget about the fact that the frontal lobes - the most
developed part of the brain - are at the same time our greatest weakness, exposed
to the action of damaging factors in our evolving environment. Is depression the
cost of evolution?
PMID- 28500858
TI - The Coumarin-Dimer Spring-The Struggle between Charge Transfer and Steric
Interactions.
AB - The synthesis of a weakly coupled, strongly polarized coumarin dimer has been
achieved for the first time. The three-step strategy comprises the Skattebol
formylation followed by the Knoevenagel reaction and the formation of a tertiary
amide by using a peptide-type procedure. The molecule consists of two different
coumarin moieties: One is a classical donor-acceptor system and the second one
possesses a weaker amide donor at the 7-position. The polarized coumarin dimer
can form an electronically conjugated structure possessing an electric dipole
larger than that of 7-(dimethylamino)coumarin-3-carboxylic acid. The limited
flexibility of the inter-coumarin connection results in stable conformers of
different electric dipole moments and complex photophysics. In the solid state,
this compound has a strongly bent conformation with the two coumarin units
forming an angle of around 74 degrees . In solution, two conformers are in
equilibrium. The existence of the molecule as two conformers in the ground state
has been confirmed by optical studies, and further corroborated by molecular
calculations. The fluorescence spectra possess a unique feature: A charge
transfer band (ca. 550 nm) is visible only in nonpolar or weakly polar solvents.
Optical spectroscopy studies coupled with molecular calculations allowed us to
rationalize this phenomenon: The large amplitude of intramolecular motions is
responsible for the conformational isomerization as well as producing a conical
intersection between the potential energy surfaces of the excited singlet state
and the ground state, which opens an internal conversion channel that effectively
competes with the fluorescence of the conformers.
PMID- 28500857
TI - Polydimethylsiloxane-based optical waveguides for tetherless powering of floating
microstimulators.
AB - Neural electrodes and associated electronics are powered either through
percutaneous wires or transcutaneous powering schemes with energy harvesting
devices implanted underneath the skin. For electrodes implanted in the spinal
cord and the brain stem that experience large displacements, wireless powering
may be an option to eliminate device failure by the breakage of wires and the
tethering of forces on the electrodes. We tested the feasibility of using
optically clear polydimethylsiloxane (PDMS) as a waveguide to collect the light
in a subcutaneous location and deliver to deeper regions inside the body, thereby
replacing brittle metal wires tethered to the electrodes with PDMS-based optical
waveguides that can transmit energy without being attached to the targeted
electrode. We determined the attenuation of light along the PDMS waveguides as
0.36 +/- 0.03 ?? dB / cm and the transcutaneous light collection efficiency of
cylindrical waveguides as 44 % +/- 11 % by transmitting a laser beam through the
thenar skin of human hands. We then implanted the waveguides in rats for a month
to demonstrate the feasibility of optical transmission. The collection efficiency
and longitudinal attenuation values reported here can help others design their
own waveguides and make estimations of the waveguide cross-sectional area
required to deliver sufficient power to a certain depth in tissue.
PMID- 28500859
TI - Proteins with Site-Specific Lysine Methylation.
AB - As an important epigenetic mark, lysine methylations play critical roles in the
regulation of both chromatin and non-chromatin proteins. There are three levels
of lysine methylation, mono-, di-, and trimethylation. Each one has turned out to
be biologically distinctive. For the biochemical characterization of proteins
with lysine methylation, multiple chemical biology methods have been developed.
This concept article will highlight these developments and their applications in
epigenetic investigation of protein functions.
PMID- 28500861
TI - Overview of high-risk medical device recalls in obstetrics and gynecology from
2002 through 2016: implications for device safety.
AB - The field of women's health has endured numerous recent controversies involving
medical devices such as pelvic meshes, laparoscopic morcellators, and a
hysteroscopic sterilization device. With the recent passage of the 21st Century
Cures Act, new legislation will change how the Food and Drug Administration
regulates medical devices. Given these controversies and new changes, we
investigated high-risk, class I recalls in women's health from 2002 through 2016.
Class I recalls for medical devices are defined by the Food and Drug
Administration as the most serious recall events and are designated for
situations when there is a reasonable probability of serious adverse health
consequences or death. We defined a recall event as a group of unique Food and
Drug Administration recalls that share a similar reason for recall and occurred
within a 1-month time frame. In total, 7 class I recall events were identified
encompassing 83 unique recalls affecting >88,000 medical devices in distribution.
Recalls involved a broad range of devices used in women's health including
diagnostic assays for chlamydia and gonorrhea, a laparoscopic tissue morcellator,
and obstetrical/gynecological surgical kits. Four of 7 (57%) recall events were
due to postmarketing problems such as improper packaging and labeling while the
remaining 3 (43%) recalls were due to premarketing problems (eg, software
issues). Additionally, 3 of 7 (43%) recall events were cleared via the 510(k)
pathway, while the remaining were essentially exempt from any form of premarket
approval. Two recall events involved sterility concerns of 71 surgical kits used
in obstetrics and gynecological surgeries representing the majority of affected
devices (78,423) in distribution. Class I medical device recalls are rare but
serious events. Most recalled devices in women's health had minimal preapproval
regulation and were recalled due to both premarketing and postmarketing reasons.
Future regulatory efforts to improve postmarketing surveillance may mitigate the
potential impact and frequency of class I recalls, but do not replace the need
for a higher burden of proof for both safety and efficacy prior to medical device
approval.
PMID- 28500860
TI - Interventions for preventing silent cerebral infarcts in people with sickle cell
disease.
AB - BACKGROUND: Sickle cell disease (SCD) is one of the commonest severe monogenic
disorders in the world, due to the inheritance of two abnormal haemoglobin (beta
globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary
complications, and premature death. Silent cerebral infarcts are the commonest
neurological complication in children and probably adults with SCD. Silent
cerebral infarcts also affect academic performance, increase cognitive deficits
and may lower intelligence quotient. OBJECTIVES: To assess the effectiveness of
interventions to reduce or prevent silent cerebral infarcts in people with SCD.
SEARCH METHODS: We searched for relevant trials in the Cochrane Library, MEDLINE
(from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980),
and ongoing trial databases; all searches current to 19 September 2016. We
searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials
Register: 06 October 2016. SELECTION CRITERIA: Randomised controlled trials
comparing interventions to prevent silent cerebral infarcts in people with SCD.
There were no restrictions by outcomes examined, language or publication status.
DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological
procedures. MAIN RESULTS: We included five trials (660 children or adolescents)
published between 1998 and 2016. Four of the five trials were terminated early.
The vast majority of participants had the haemoglobin (Hb)SS form of SCD. One
trial focused on preventing silent cerebral infarcts or stroke; three trials were
for primary stroke prevention and one trial dealt with secondary stroke
prevention.Three trials compared the use of regular long-term red blood cell
transfusions to standard care. Two of these trials included children with no
previous long-term transfusions: one in children with normal transcranial doppler
(TCD) velocities; and one in children with abnormal TCD velocities. The third
trial included children and adolescents on long-term transfusion.Two trials
compared the drug hydroxyurea and phlebotomy to long-term transfusions and iron
chelation therapy: one in primary prevention (children), and one in secondary
prevention (children and adolescents).The quality of the evidence was moderate to
very low across different outcomes according to GRADE methodology. This was due
to trials being at high risk of bias because they were unblinded; indirectness
(available evidence was only for children with HbSS); and imprecise outcome
estimates. Long-term red blood cell transfusions versus standard care Children
with no previous long-term transfusions and higher risk of stroke (abnormal TCD
velocities or previous history of silent cerebral infarcts) Long-term red blood
cell transfusions may reduce the incidence of silent cerebral infarcts in
children with abnormal TCD velocities, risk ratio (RR) 0.11 (95% confidence
interval (CI) 0.02 to 0.86) (one trial, 124 participants, low-quality evidence);
but make little or no difference to the incidence of silent cerebral infarcts in
children with previous silent cerebral infarcts on magnetic resonance imaging and
normal or conditional TCDs, RR 0.70 (95% CI 0.23 to 2.13) (one trial, 196
participants, low-quality evidence).No deaths were reported in either trial.Long
term red blood cell transfusions may reduce the incidence of: acute chest
syndrome, RR 0.24 (95% CI 0.12 to 0.49) (two trials, 326 participants, low
quality evidence); and painful crisis, RR 0.63 (95% CI 0.42 to 0.95) (two trials,
326 participants, low-quality evidence); and probably reduces the incidence of
clinical stroke, RR 0.12 (95% CI 0.03 to 0.49) (two trials, 326 participants,
moderate-quality evidence).Long-term red blood cell transfusions may improve
quality of life in children with previous silent cerebral infarcts (difference
estimate -0.54; 95% confidence interval -0.92 to -0.17; one trial; 166
participants), but may have no effect on cognitive function (least squares means:
1.7, 95% CI -1.1 to 4.4) (one trial, 166 participants, low-quality evidence).
Transfusions continued versus transfusions halted: children and adolescents with
normalised TCD velocities (79 participants; one trial)Continuing red blood cell
transfusions may reduce the incidence of silent cerebral infarcts, RR 0.29 (95%
CI 0.09 to 0.97 (low-quality evidence).We are very uncertain whether continuing
red blood cell transfusions has any effect on all-cause mortality, Peto odds
ratio (OR) 8.00 (95% CI 0.16 to 404.12); or clinical stroke, RR 0.22 (95% CI 0.01
to 4.35) (very low-quality evidence).The trial did not report: comparative
numbers for SCD-related adverse events; quality of life; or cognitive function.
Hydroxyurea and phlebotomy versus transfusions and chelation Primary prevention,
children (121 participants; one trial)We are very uncertain whether switching to
hydroxyurea and phlebotomy has any effect on: silent cerebral infarcts (no
infarcts); all-cause mortality (no deaths); risk of stroke (no strokes); or SCD
related complications, RR 1.52 (95% CI 0.58 to 4.02) (very low-quality evidence).
Secondary prevention, children and adolescents with a history of stroke (133
participants; one trial)We are very uncertain whether switching to hydroxyurea
and phlebotomy has any effect on: silent cerebral infarcts, Peto OR 7.28 (95% CI
0.14 to 366.91); all-cause mortality, Peto OR 1.02 (95%CI 0.06 to 16.41); or
clinical stroke, RR 14.78 (95% CI 0.86 to 253.66) (very low-quality
evidence).Switching to hydroxyurea and phlebotomy may increase the risk of SCD
related complications, RR 3.10 (95% CI 1.42 to 6.75) (low-quality
evidence).Neither trial reported on quality of life or cognitive function.
AUTHORS' CONCLUSIONS: We identified no trials for preventing silent cerebral
infarcts in adults, or in children who do not have HbSS SCD.Long-term red blood
cell transfusions may reduce the incidence of silent cerebral infarcts in
children with abnormal TCD velocities, but may have little or no effect on
children with normal TCD velocities. In children who are at higher risk of stroke
and have not had previous long-term transfusions, long-term red blood cell
transfusions probably reduce the risk of stroke, and other SCD-related
complications (acute chest syndrome and painful crises).In children and
adolescents at high risk of stroke whose TCD velocities have normalised,
continuing red blood cell transfusions may reduce the risk of silent cerebral
infarcts. No treatment duration threshold has been established for stopping
transfusions.Switching to hydroxyurea with phlebotomy may increase the risk of
silent cerebral infarcts and SCD-related serious adverse events in secondary
stroke prevention.All other evidence in this review is of very low-quality.
PMID- 28500862
TI - Enhanced Tau Aggregation in the Presence of Amyloid beta.
AB - Amyloid plaques and neurofibrillary tangles co-occur in Alzheimer disease, but
with different topological and temporal patterns. Whether these two lesions are
independent or pathobiologically related is uncertain. For example, amyloid
deposition in the neocortex precedes the spread of tau neurofibrillary tangles
from the limbic areas to the cortex. We examined the aggregation properties of
tau isolated from human cases with early tau pathology (Braak II) with and
without plaques. Using a well-established HEK cell biosensor assay, we show that
tau from cases with plaques has an enhanced ability to induce tau aggregates
compared to tau from cases without plaques. To further explore this effect, we
combined mice carrying the APP/PS1 transgene array that develop plaques with
rTg4510 mice carrying the P301L mutant human tau transgene that develop extensive
tau pathology with age. The resulting APP/PS1-rTg4510 mice had a threefold
increase in tau seeding activity over the rTg4510 strain, without change in tau
production or extracellular release. Surprisingly, this effect was observed
before overt amyloid deposition. The enhancement of tau aggregation was also
apparent by an increase in histological measures of tau pathology in young
APP/PS1-rTg4510 mice and an increase in high-molecular-weight tau. Overall, these
data provide evidence that amyloid beta acts to enhance tau pathology by
increasing the formation of tau species capable of seeding new aggregates.
PMID- 28500863
TI - Lymphoepithelioma-Like Carcinoma in Liver.
AB - Liver cancer, primarily encompassing hepatocellular carcinoma and intrahepatic
cholangiocarcinoma, has become the second leading cause of worldwide cancer
related death during the past two decades. Lymphoepithelioma-like carcinomas
(LELCs) are defined as tumors composed of undifferentiated epithelial cells with
a prominent lymphoid infiltrate, and can arise in the liver as hepatocellular or
cholangiocarcinoma forms. Patients with liver LELC display distinctive
demographics and tumor characteristics. LELCs also appear to be associated with
strikingly better outcomes compared to typical liver cancers, with 5-year
survival rates of 57% to 100% versus 12% to 68%, respectively. Liver LELCs
represent a unique model of immune response in liver cancer. Data on LELCs of the
liver remain limited, and future comprehensive studies are needed to further
elucidate this disease, which could ultimately offer precious insights for
immunotherapeutic strategies in liver cancer.
PMID- 28500864
TI - Identification of Human Bocavirus type 4 in a child asymptomatic for respiratory
tract infection and acute gastroenteritis - Goiania, Goias, Brazil.
AB - Human Bocavirus (HBoV) has been identified from feces and respiratory samples
from cases of both acute gastroenteritis and respiratory illness as well as in
asymptomatic individuals. The aim of this study was to detect and characterize
HBoV from fecal samples collected from hospitalized children aged less than five
years old with no symptoms of respiratory tract infection (RTI) or acute
gastroenteritis (AGE). The study involved 119 children and one fecal sample was
collected from each participant between 2014 and 2015. HBoV was detected using
Nested-PCR, and the viral type identified by genomic sequencing. HBoV-4 was
identified from one sample obtained from a hospitalized child with soft tissue
tumor of the submandibular region. This is the first report of HBoV-4
identification in Brazil, but we consider that this type may be circulating in
the country similar to the other types and new investigations are necessary.
PMID- 28500865
TI - Dihydromyricetin ameliorates atherosclerosis in LDL receptor deficient mice.
AB - BACKGROUND AND AIMS: Dihydromyricetin, the most abundant flavonoid in Ampelopsis
grossedentata, exerts numerous pharmacological activities, including anti
inflammatory, antioxidant, hepatoprotective, and lipid regulatory activities;
however, its protective effect against atherosclerosis remains poorly understood.
The aim of the present study was to evaluate the effects of dihydromyricetin on
high fat diet (HFD)-induced atherosclerosis using LDL receptor deficient (LDLr-/
) mice. METHODS: Blood samples were collected for determination of serum lipid
profiles, oxidized LDL (ox-LDL) and pro-inflammatory cytokines. Histology,
hepatic lipid content, quantification of atherosclerosis, assessment of oxidative
stress and inflammation were performed on liver and aorta samples by molecular
biology methods. The effects of dihydromyricetin on ox-LDL-induced human
umbilical vein endothelial cells (HUVECs) dysfunction and foam cell formation
were further studied. RESULTS: (1) Dihydromyricetin ameliorated hyperlipidemia,
reduced serum ox-LDL, IL-6 and TNF-alpha levels in HFD-fed LDLr-/- mice.
Moreover, (2) dihydromyricetin suppressed hepatic lipid accumulation and
increased protein expressions of PPARalpha, LXRalpha and ABCA1. (3) It inhibited
atherosclerotic lesion formation and favoured features of plaque stability. (4)
Dihydromyricetin prevented hepatic and aortic inflammation as evidenced by the
reduced IL-6 and TNF-alpha mRNA expression; (5) it prevented hepatic and aortic
oxidative stress by normalizing activities of antioxidant enzymes in the liver
and suppressing reactive oxygen species generation and NOX2 protein expression in
both liver and aorta; (6) it inhibited oxLDL-induced injury, monocytes adhesion
and oxidative stress in HUVECs and (7) inhibited macrophage foam cell formation
and enhanced cholesterol efflux. CONCLUSIONS: These findings suggest that
dihydromyricetin could reduce atherosclerosis via its pleiotropic effects,
including improvement of endothelial dysfunction, inhibition of macrophage foam
cell formation, amelioration of lipid profiles, anti-inflammatory action and anti
oxidative effect.
PMID- 28500866
TI - Presence of eating disorders and its relationship to anxiety and depression in
pregnant women.
AB - BACKGROUND: women who have inadequate nutrient intake are more likely to develop
a risky pregnancy. The purpose of this study was to determine the presence of
eating disorders and its association with anxiety and depression symptomatology
in high-risk pregnancies. METHODS: this is a cross-sectional and prospective
study conducted at the tertiary university hospital in the city of Sao Paulo,
Brazil. 913 pregnant women waiting for the Obstetrics' outpatient appointment
were invited to participate in the study on their 2nd and 3rd trimester of
pregnancy. Structured interviews were carried out and the Structured Clinical
Interview for DSM Disorders and Hospital Anxiety and Depression Scale were
applied. FINDINGS: prevalence of eating disorder (ED) during pregnancy was 7.6%
(n=69) (95% CI: 5.84% -9.28%), 0.1% (n=1) for anorexia nervosa; 0.7% (n=6) for
bulimia nervosa; 1.1% (n=10) for binge eating disorder, and 5.7% (n=52) for pica.
A statistically significant difference was found between the anxiety (p<0.01) and
depressive symptoms (p<0.01). CONCLUSIONS: the prevalence of ED (7.6%) and its
association with anxiety and depression symptoms during pregnancy highlights the
need for specialist care for prevention, diagnosis and treatment. Given the
importance of proper nutrition during pregnancy, both with regard to maternal
health and fetal development, it is necessary to have specific predetermined
evaluation protocols implemented by health care professionals for the diagnosis
of ED during pregnancy.
PMID- 28500867
TI - Hospitalization for Charcot neuroarthropathy in diabetes: A population study in
Italy.
AB - AIMS: To provide data on hospitalization and incidence rates of Charcot
neuroarthropathy (CN) and its relation to lower limbs'
amputations/revascularizations in population with diabetes of Italy as well as of
one of its regions (Tuscany). METHODS: Hospitalizations with CN diagnosis (codes
ICD-9-CM: 7130, 7135, 7138) have been recorded in people with diabetes over years
2003-2013 in Italy and 2008-2015 in Tuscany. Amputations, peripheral vascular
disease, revascularizations and infections were likewise evaluated. RESULTS:
Between 2003 and 2013 CN hospitalizations were very infrequent in Italy ranging
between 14*100,000 and 11*100,000 patients with diabetes. In Tuscany they
declined to a minimum of 7*100,000 patients in 2015, after a previous increase to
a maximum of 22*100,000 (p=NS for both). Yearly CN incidence remained constant in
Italy, declining in Tuscany to a minimum of 3.4*100,000 diabetic patients in 2015
(p=0.047). CN patients were younger and with longer length of hospital stay than
those with non-Charcot diabetic foot (p<0.05 for both). Amputation and infection
rates were manifold higher in CN patients than in those with non-Charcot diabetic
foot, while the revascularization rate was similar in both. CONCLUSIONS: Over
last decade, in Italy and Tuscany yearly CN incidence and hospitalization rates
concerned only a small percentage of patients, remaining constant over years and
declining in Tuscany in the last couple of years. CN was significantly associated
to younger age, longer hospital stay and greater risk of amputations and
infections while the need of revascularization was similar to that of non-Charcot
diabetic foot.
PMID- 28500868
TI - Type 1 diabetes mellitus care and education in China: The 3C study of coverage,
cost, and care in Beijing and Shantou.
AB - AIMS: The paucity of data on Type 1 diabetes in China hinders progress in care
and policy-making. This study compares Type 1 diabetes care and clinical outcomes
in Beijing and Shantou with current clinical guidelines. METHODS: The 3C Study
was a cross-sectional study of the clinical practices and outcomes of people with
Type 1 diabetes. The study sequentially enrolled 849 participants from hospital
records, inpatient wards, and outpatient clinics. Data were collected via face-to
face interviews with patients and health professionals, the Summary of Diabetes
Self-Care Activities, medical records, and venous blood samples. Care was audited
using ISPAD/IDF indicators. Data underwent descriptive analysis and tests for
association. RESULTS: The median age was 22years (IQR=13-34years), and 48.4% of
the sample had diabetes less than six years. The median HbA1c was 8.5%
(69mmol/mol) (IQR 7.2-10.5%), with significant regional variance (p=0.002).
Insulin treatment was predominantly two injections/day (45% of patients). The
highest incidence of diabetic ketoacidosis was 14.4 events/100 patient years
among adolescents. Of the 57.3% of patients with LDL-C>2.6mmol/L, only 11.2%
received treatment. Of the 10.6% considered hypertensive, 47.1% received
treatment. Rates of documented screening for retinopathy, nephropathy, and
peripheral neuropathy were 35.2%, 42.3%, and 25.0%, respectively. The median
number of days of self-monitoring/week was 3.0 (IQR=1.0-7.0). There were
significant differences in care practices across regions. CONCLUSIONS: The study
documented an overall deficit in care with significant regional differences noted
compared to practice guidelines. Modifications to treatment modalities and the
structure of care may improve outcomes.
PMID- 28500869
TI - To sleep or not to sleep: neuronal and ecological insights.
AB - Daily, animals need to decide when to stop engaging in cognitive processes and
behavioral responses to the environment, and go to sleep. The main processes
regulating the daily organization of sleep and wakefulness are circadian rhythms
and homeostatic sleep pressure. In addition, motivational processes such as food
seeking and predator evasion can modulate sleep/wake behaviors. Here, we discuss
the principal processes regulating the propensity to stay awake or go to sleep
focusing on neuronal and behavioral aspects. We first introduce the neuronal
populations involved in sleep/wake regulation. Next, we describe the circadian
and homeostatic drives for sleep. Then, we highlight studies demonstrating
various effects of motivational processes on sleep/wake behaviors, and discuss
possible neuronal mechanisms underlying their control.
PMID- 28500871
TI - The ability to tickle oneself is associated with level of psychometric schizotypy
in non-clinical individuals.
AB - A recent study (Lemaitre et al., 2016, Consciousness and Cognition, 41, 64-71)
found that non-clinical individuals who scored highly on a psychometric scale of
schizotypy were able to tickle themselves. The present study aimed to extend this
finding by investigating whether the ability to tickle oneself was associated
with level of psychometric schizotypy considered as a continuous variable. One
hundred and eleven students completed the Schizotypal Personality Questionnaire
(SPQ). A mechanical device delivered tactile stimulation to participants' palms.
The device was operated by the experimenter (External) or the participant (Self).
Participants were asked to rate the intensity, ticklishness and pleasantness of
the stimulation. A significant association was observed between participants'
tactile self-suppression (External minus Self) and their score on the SPQ. These
results suggest that the ability to suppress the tactile consequences of self
generated movements varies across the general population, and maps directly onto
the personality dimension of schizotypy.
PMID- 28500870
TI - Brainstem regulation of slow-wave-sleep.
AB - Recent work has helped reconcile puzzling results from brainstem transection
studies first performed over 60 years ago, which suggested the existence of a
sleep-promoting system in the medullary brainstem. It was specifically shown that
GABAergic neurons located in the medullary brainstem parafacial zone (PZGABA) are
not only necessary for normal slow-wave-sleep (SWS) but that their selective
activation is sufficient to induce SWS in behaving animals. In this review we
discuss early experimental findings that inspired the hypothesis that the caudal
brainstem contained SWS-promoting circuitry. We then describe the discovery of
the SWS-promoting PZGABA and discuss future experimental priorities.
PMID- 28500873
TI - Evaluation methods for assessing effectiveness of in situ remediation of soil and
sediment contaminated with organic pollutants and heavy metals.
AB - Soil and sediment contamination has become a critical issue worldwide due to its
great harm to the ecological environment and public health. In recent years, many
remediation technologies including physical, chemical, biological, and combined
methods have been proposed and adopted for the purpose of solving the problems of
soil and sediment contamination. However, current research on evaluation methods
for assessing these remediation technologies is scattered and lacks valid and
integrated evaluation methods for assessing the remediation effectiveness. This
paper provides a comprehensive review with an environmental perspective on the
evaluation methods for assessing the effectiveness of in situ remediation of soil
and sediment contaminated with organic pollutants and heavy metals. The review
systematically summarizes recent exploration and attempts of the remediation
effectiveness assessment based on the content of pollutants, soil and sediment
characteristics, and ecological risks. Moreover, limitations and future research
needs of the practical assessment are discussed. These limitations are not
conducive to the implementation of the abatement and control programs for soil
and sediment contamination. Therefore, more attention should be paid to the
evaluation methods for assessing the remediation effectiveness while developing
new in situ remediation technologies in future research.
PMID- 28500874
TI - Effects of Intermittent Low-Dose Parathyroid Hormone Treatment on Rapid
Mandibular Distraction Osteogenesis in Rabbits.
AB - PURPOSE: To determine whether low-dose recombinant human parathyroid hormone
(rhPTH) would have a beneficial effect on regenerate healing and surrounding bone
in a rabbit model of rapid mandibular distraction osteogenesis (DO). MATERIALS
AND METHODS: Twenty-eight rabbits underwent unilateral mandibular lengthening at
a rapid rate of 2 mm per day for 5 days. From the first day of DO, the
experimental group received daily subcutaneous injections of rhPTH 10 MUg/kg for
30 days and the control group received the same volume of saline (n = 14 in each
group). At 6 weeks after completion of DO, the distracted callus was examined by
micro-computed tomography (micro-CT), histology, and the 3-point bending test.
Moreover, bone mineral density of the anterior pin region was evaluated by dual
energy x-ray absorptiometry. RESULTS: Under rapid distraction, poor bone healing
was observed in the distracted callus from the control group. In contrast, more
mature and abundant bone formation was found in the distracted callus from the
experimental group by histologic and micro-CT examinations. Quantitatively, the
PTH-treated animals had superior parameters in bone volume fraction, trabecular
number, and trabecular thickness and mechanical properties compared with controls
(P < .05). Bone mineral density of the anterior pin region was greater in the
experimental than in the control group (P < .05). CONCLUSION: Low-dose
intermittent rhPTH administration not only enhances new bone formation but also
can prevent fixator-related osteoporosis of surrounding segments after rapid
mandibular DO in rabbits.
PMID- 28500872
TI - CYP3A genes and the association between prenatal methylmercury exposure and
neurodevelopment.
AB - BACKGROUND: Results on the association between prenatal exposure to methylmercury
(MeHg) and child neuropsychological development are heterogeneous. Underlying
genetic differences across study populations could contribute to this varied
response to MeHg. Studies in Drosophila have identified the cytochrome p450 3A
(CYP3A) family as candidate MeHg susceptibility genes. OBJECTIVES: We evaluated
whether genetic variation in CYP3A genes influences the association between
prenatal exposure to MeHg and child neuropsychological development. METHODS: The
study population included 2639 children from three birth cohort studies: two
subcohorts in Seychelles (SCDS) (n=1160, 20 and 30months of age, studied during
the years 2001-2012), two subcohorts from Spain (INMA) (n=625, 14months of age,
2003-2009), and two subcohorts from Italy and Greece (PHIME) (n=854, 18months of
age, 2006-2011). Total mercury, as a surrogate of MeHg, was analyzed in maternal
hair and/or cord blood samples. Neuropsychological development was evaluated
using Bayley Scales of Infant Development (BSID). Three functional polymorphisms
in the CYP3A family were analyzed: rs2257401 (CYP3A7), rs776746 (CYP3A5), and
rs2740574 (CYP3A4). RESULTS: There was no association between CYP3A polymorphisms
and cord mercury concentrations. The scores for the BSID mental scale improved
with increasing cord blood mercury concentrations for carriers of the most active
alleles (beta[95% CI]:=2.9[1.53,4.27] for CYP3A7 rs2257401 GG+GC, 2.51[1.04,3.98]
for CYP3A5 rs776746 AA+AG and 2.31[0.12,4.50] for CYP3A4 rs2740574 GG+AG). This
association was near the null for CYP3A7 CC, CYP3A5 GG and CYP3A4 AA genotypes.
The interaction between the CYP3A genes and total mercury was significant
(p<0.05) in European cohorts only. CONCLUSIONS: Our results suggest that the
polymorphisms in CYP3A genes may modify the response to dietary MeHg exposure
during early life development.
PMID- 28500875
TI - Upper Airway Changes After Mandibular Setback and/or Advancement Genioplasty in
Obese Patients.
AB - PURPOSE: Orthognathic surgeries, such as bilateral sagittal split ramus osteotomy
(BSSO) and genioplasty, can influence the pharyngeal airway space (PAS) and this
has been supported by previous studies. The purpose of this study was to assess
changes of the PAS in patients with a high body mass index (BMI) likely to have
narrow airways before and after setback BSSO with or without advancement
genioplasty surgery by 3-dimensional computed tomography. MATERIALS AND METHODS:
Thirty-five adults with a BMI of at least 24.0 kg/m2 were treated from 2010 to
2016. Samples were grouped mandibular setback (group A; n = 11), advancement
genioplasty (group B; n = 12), and mandibular setback plus advancement
genioplasty (group C; n = 12). Computed tomograms were obtained 1 week
preoperatively (T0), 1 week postoperatively (T1), and at least 1 year
postoperatively (T2). The area of the posterior nasal spine and posterior plane
(PPA), the soft palate plane (SPA), the plane of the most posterior point of the
tongue base (PTA), the plane of the root of the epiglottis (EA), and the volumes
of the palatopharyngeal part (VP), oropharyngeal part (VO), glossopharyngeal part
(VG), and laryngeal part (VL) were measured and compared within groups using
analysis of variance. The P value was set at .05. RESULTS: In group A, all
results showed statistically significant differences (P < .05) from T0 to T2
except for VO, VG, VL, SPA, PTA, and EA. In group B, VO, VG, VL, SPA, PTA, and EA
showed statistically significant increases (P < .05) from T0 to T2. The hyoid at
T2 showed significant advancement compared with T0 (P < .05). In group C, there
were statistically significant decreases (P < .05) from T0 to T1 for VG, VL, PTA,
and EA. CONCLUSION: In adults with a high BMI, mandibular setback BSSO could
decrease the PAS, whereas advancement genioplasty could enlarge the PAS, after
surgery. Therefore, undergoing advancement genioplasty concurrently with
mandibular setback BSSO could help in lessening the negative effects of a PAS
decrease.
PMID- 28500876
TI - Does Adjunctive Botulinum Toxin A Reduce Pain Scores When Combined With
Temporomandibular Joint Arthroscopy for the Treatment of Concomitant
Temporomandibular Joint Arthralgia and Myofascial Pain?
AB - PURPOSE: Currently, there is no standard of care for the treatment of refractory
myofascial pain and concomitant temporomandibular joint (TMJ) arthralgia. This
comparative study was conducted to determine the effectiveness of botulinum toxin
A (Btx), as an adjunct to TMJ arthroscopy, in this patient population. MATERIALS
AND METHODS: A retrospective cohort study was conducted of patients who underwent
TMJ arthroscopy with (Btx group) or without (control group) intramuscular Btx for
TMJ arthritis and refractory myofascial pain at the University of Michigan (Ann
Arbor) from 2011 through 2014. For patients in the Btx group, intramuscular
injections of Btx were administered at sites of maximal tenderness within the
masseter and temporalis muscles. The primary outcome variable was pain score on
the visual analog scale (VAS; 0 to 10). The secondary outcome variables included
maximal interincisal opening, total score for sites of tenderness, total number
of tender sites, and diet consistency tolerated. Statistical analysis included
means and standard deviations, Student t test, simple regression analysis, and
multiple regression analysis. RESULTS: The study cohort included 52 patients (30
in Btx group, 22 in control group), of which 48 (92.3%) were women. The mean
follow-up was 5.56 +/- 1.41 months. Patients in the Btx group had a significantly
greater decrease in mean pain score (P = .04) on the VAS compared with the
control group (score, 3.24 for Btx group; score, 1.13 for control group). On
multivariate regression analysis, treatment with Btx trended toward significance
(P = .084) and the preoperative pain score (P = .0007) was significantly
correlated with the change in pain observed. CONCLUSION: The use of Btx appears
to correlate with a clinically superior decrease in pain score compared with the
control group. The use of Btx could be useful as an adjunctive treatment modality
in the management of refractory myofascial pain.
PMID- 28500877
TI - Clinically isolated aortitis: pitfalls, progress, and possibilities.
AB - Non-infectious aortitis may be caused by several distinct systemic rheumatologic
diseases. In some patients, aortitis is identified either pathologically or
radiologically in the absence of clinical evidence of a systemic vasculitis. By
consensus nomenclature, such cases are referred to as clinically isolated
aortitis (CIA). Some systemic disorders may initially present as CIA including
giant cell arteritis (GCA), IgG4-related disease, infectious aortitis, and
granulomatosis with polyangiitis. CIA most commonly occurs in women of European
descent over the age of 50 and, thus, mirrors the gender, age, and geographic
distribution of GCA. CIA most often demonstrates a granulomatous/giant cell
pattern of inflammation (GPI), and CIA-GPI is pathologically indistinguishable
from aortitis due to GCA. In many cases, CIA may be a manifestation of
extracranial GCA. CIA is being identified both pathologically in resected aortic
tissue and radiologically by computed tomography scanning, magnetic resonance
imaging, and fluorodeoxyglucose positron emission tomography. However, there
appears to be significant differences between pathologically defined CIA and
radiologically defined CIA. Multiple studies have shown that patients with CIA
are at increased risk for subsequent aortic events (new aneurysms or dissections)
and thus it is recommended to monitor these patients with periodic aortic
imaging. While the data is currently limited, there is increasing evidence that
at least some patients with CIA may benefit from immunosuppressive therapy.
PMID- 28500878
TI - Identification of changes in neuronal function as a consequence of aging and
tauopathic neurodegeneration using a novel and sensitive magnetic resonance
imaging approach.
AB - Tauopathies, the most common of which is Alzheimer's disease (AD), constitute the
most crippling neurodegenerative threat to our aging population. Tauopathic
patients have significant cognitive decline accompanied by irreversible and
severe brain atrophy, and it is thought that neuronal dysfunction begins years
before diagnosis. Our current understanding of tauopathies has yielded promising
therapeutic interventions but have all failed in clinical trials. This is partly
due to the inability to identify and intervene in an effective therapeutic window
early in the disease process. A major challenge that contributes to the
definition of an early therapeutic window is limited technologies. To address
these challenges, we modified and adapted a manganese-enhanced magnetic resonance
imaging (MEMRI) approach to provide sensitive and quantitative power to detect
changes in broad neuronal function in aging mice. Considering that tau tangle
burden correlates well with cognitive impairment in Alzheimer's patients, we
performed our MEMRI approach in a time course of aging mice and an accelerated
mouse model of tauopathy. We measured significant changes in broad neuronal
function as a consequence of age, and in transgenic mice, before the deposition
of bona fide tangles. This MEMRI approach represents the first diagnostic measure
of neuronal dysfunction in mice. Successful translation of this technology in the
clinic could serve as a sensitive diagnostic tool for the definition of effective
therapeutic windows.
PMID- 28500879
TI - Role of forensic medicine in evaluating non-fatal physical violence against women
by their husbands in Jordan.
AB - OBJECTIVE: Intimate partner violence against women is a major health problem in
most nations, but to date, there has been little awareness of the extent or
seriousness of this issue in Jordan. Forensic medical practitioners play a
significant role in diagnosing, evaluating and reporting these cases. The
Jordanian judicial system is dependent on forensic reports. This study aims to
assess the role of forensic medicine in evaluating the physical injuries
sustained by women who are abused by their husbands. METHOD: A retrospective
review of 158 forensic reports of Jordanian women alleging assault by their
husbands and who were seen at Jordan University Hospital over the period 2010
2015. RESULTS: Of the 158 women who presented, 87 had multiple injuries. The
majority of injuries were soft tissue injuries, but others included fractures,
tympanic membrane perforation, burns and neck contusions. Twelve women were
pregnant at the time of the assessment. The period of incapacity caused by these
injuries (an important factor for the Jordanian judicial system) was between 1
and 14 days. CONCLUSION: Intimate partner violence can present with a range of
injuries from relatively minor to potentially disabling or life threatening.
Forensic medicine has a role in documenting and evaluating these injuries and
advising the judicial system in these cases. These are all key elements in
increasing the awareness of the nature and extent of this behavior and its impact
on women (and men) and the wider society.
PMID- 28500880
TI - Motor functioning differentially predicts mortality in men and women.
AB - INTRODUCTION: Research indicates gender differences in functional performance at
advanced ages, but little is known about their impact on longevity for men and
women. OBJECTIVE: To derive a set of motor function factors from a battery of
functional performance measures and examine their associations with mortality,
incorporating possible gender interactions. METHOD: Analyses were performed on
the longitudinal Swedish Adoption/Twin Study of Aging (SATSA) including twenty
four assessments of motor function up to six times over a 19-year period. Three
motor factors were derived from several factor analyses; fine motor,
balance/upper strength, and flexibility. A latent growth curve model was used to
capture longitudinal age changes in the motor factors and generated estimates of
intercept at age 70 (I), rates of change before (S1) and after age 70 (S2) for
each factor. Cox regression models were used to determine how gender in
interaction with the motor factors was related to mortality. RESULTS: Females
demonstrated lower functional performance in all motor functions relative to men.
Cox regression survival analyses demonstrated that both balance/upper strength,
and fine motor function were significantly related to mortality. Gender specific
analyses revealed that this was true for women only. For men, none of the motor
factors were related to mortality. CONCLUSION: Women demonstrated more
difficulties in all functioning facets, and only among women were motor
functioning (balance/upper strength and fine motor function) associated with
mortality. These results provide evidence for the importance of considering motor
functioning, and foremost observed gender differences when planning for
individualized treatment and rehabilitation.
PMID- 28500881
TI - A Parvovirus B19 synthetic genome: sequence features and functional competence.
AB - Central to genetic studies for Parvovirus B19 (B19V) is the availability of
genomic clones that may possess functional competence and ability to generate
infectious virus. In our study, we established a new model genetic system for
Parvovirus B19. A synthetic approach was followed, by design of a reference
genome sequence, by generation of a corresponding artificial construct and its
molecular cloning in a complete and functional form, and by setup of an efficient
strategy to generate infectious virus, via transfection in UT7/EpoS1 cells and
amplification in erythroid progenitor cells. The synthetic genome was able to
generate virus with biological properties paralleling those of native virus, its
infectious activity being dependent on the preservation of self-complementarity
and sequence heterogeneity within the terminal regions. A virus of defined genome
sequence, obtained from controlled cell culture conditions, can constitute a
reference tool for investigation of the structural and functional characteristics
of the virus.
PMID- 28500883
TI - Effect of temperature, water loading, and Ru/C catalyst on water-insoluble and
water-soluble biocrude fractions from hydrothermal liquefaction of algae.
AB - Hydrothermal liquefaction (HTL) converts algal biomass into a crude bio-oil
(biocrude) and aqueous-phase products. The effect of temperature, water loading,
and added H2 and/or Ru/C catalyst on the properties of the biocrude that
spontaneously separates from the aqueous phase post reaction and also the
biocrude that is extractable from the aqueous phase by dichloromethane is
explored herein. This report is the first to elucidate how the yields,
compositions, heating values, and energy recoveries of the two biocrudes vary
with the processing conditions above. Increasing temperature from 350 to 400
degrees C increased the yield of water-insoluble biocrude (38.1-42.5wt%) and its
hexane-soluble subfraction (63.7-85.6wt%) while decreasing the yield of
extractable, water-soluble biocrude (6.6-2.5wt%). The Ru/C catalyst had the same
effect. Reaction temperature and catalysts could be used to manipulate the
proportions of water-soluble and water-insoluble biocrude from algae HTL and
thereby manipulate biocrude quantity and quality.
PMID- 28500882
TI - Human papillomavirus 16 E6 and E7 oncoprotein expression alters microRNA
expression in extracellular vesicles.
AB - Extracellular vesicles released by cancer cells are mediators of intercellular
communication that have been reported to contribute to carcinogenesis. Since they
are readily detected in bodily fluids, they may also be used as cancer
biomarkers. The E6/E7 oncoproteins drive human papillomavirus (HPV)-associated
cancers, which account for approximately 5% of all human cancers worldwide. Here,
we investigate how HPV16 E6/E7 oncogene expression in primary human epithelial
cells alters miR expression in extracellular vesicles and compare these to
changes in intracellular miR expression. Examining a panel of 68 cancer related
miRs revealed that many miRs had similar expression patterns in cells and in
extracellular vesicles, whereas some other miRs had different expression patterns
and may be selectively packaged into extracellular vesicles. Interestingly, the
set of miRs that may be selectively packaged in HPV16 E6/E7 extracellular
vesicles is predicted to inhibit necrosis and apoptosis.
PMID- 28500884
TI - Rapid biodiesel synthesis from waste pepper seeds without lipid isolation step.
AB - In situ transformation of lipid in waste pepper seeds into biodiesel (i.e., fatty
acid methyl esters: FAMEs) via thermally-induced transmethylation on silica was
mainly investigated in this study. This study reported that waste pepper seeds
contained 26.9wt% of lipid and that 94.1% of the total lipid in waste pepper
seeds could be converted into biodiesel without lipid extraction step for only
~1min reaction time. This study also suggested that the optimal temperature for
in situ transmethylation was identified as 390 degrees C. Moreover, comparison of
in situ process via the conventional transmethylation catalyzed by H2SO4 showed
that the introduced biodiesel conversion in this study had a higher tolerance
against impurities, thereby being technically feasible. The in situ biodiesel
production from other oil-bearing food wastes can be studied.
PMID- 28500885
TI - Effects of ZnO nanoparticles on aerobic denitrification by strain Pseudomonas
stutzeri PCN-1.
AB - Anaerobic denitrification has been proved to be negatively affected by ZnO
nanomaterials (NPs), but little is known about how ZnO NPs affects aerobic
denitrification. In this study, inhibition of ZnO NPs to an aerobic denitrifier,
Pseudomonas stutzeri PCN-1, was firstly reported. The results showed total
nitrogen removal efficiency was decreased from 100% to 1.70% with the increase of
ZnO NPs from 1 to 128mg/L. The presence of ZnO NPs caused significant inhibition
of gene expressions and catalytic activities of nitrate reductase and nitrite
reductase, which finally led to delayed nitrate reduction and high nitrite
accumulation. Further studies revealed that the deposition of nanoparticles on
the bacterial surface caused by electrostatic forces and the generation of
reactive oxygen species (ROS) were responsible for the cytotoxicity of ZnO NPs,
where ROS played a more important role. These results were of significance to
evaluating the potential ecological toxicity and risks of nanomaterials.
PMID- 28500886
TI - Optimized removal of oxytetracycline and cadmium from contaminated waters using
chemically-activated and pyrolyzed biochars from forest and wood-processing
residues.
AB - In the present investigation, the adsorptive removal of the antibiotic drug
oxytetracycline (OTC) and toxic heavy metal cadmium (Cd) from aqueous solution
was carried out using forest and wood-processing residues. Numerous biochars were
prepared using different chemical agents (H3PO4, H2SO4, NaOH and KOH) and
pyrolysis times and temperatures. Several elemental, chemical and structural
characterizations were performed. The optimum conditions for pyrolysis to enable
the production of biochars with well-developed porosity was 600 degrees C for 1h,
for both residues. The adsorption process using selected activated biochars was
optimized with respect to reaction time, pH, temperature and initial load of
pollutants. Under optimized operating conditions, and based on equilibrium
modelling data, the biochars which showed the highest removal efficiencies of OTC
and cadmium were "5M H3PO4 forest" (263.8mg/g) and "1M NaOH forest" (79.30mg/g),
respectively. Compared to adsorbents reported in the literature, the efficiencies
of those biochars are highly competitive.
PMID- 28500887
TI - Integrated techno-economic and environmental analysis of butadiene production
from biomass.
AB - In this study, lignocellulose biorefineries annexed to a typical sugar mill were
investigated to produce either ethanol (EtOH) or 1,3-butadiene (BD), utilizing
bagasse and trash as feedstock. Aspen simulation of the scenarios were developed
and evaluated in terms of economic and environmental performance. The minimum
selling prices (MSPs) for bio-based BD and EtOH production were 2.9-3.3 and 1.26
1.38-fold higher than market prices, respectively. Based on the sensitivity
analysis results, capital investment, Internal Rate of Return and extension of
annual operating time had the greatest impact on the MSP. Monte Carlo simulation
demonstrated that EtOH and BD productions could be profitable if the average of
ten-year historical price increases by 1.05 and 1.9-fold, respectively. The
fossil-based route was found inferior to bio-based pathway across all
investigated environmental impact categories, due to burdens associated with oil
extraction.
PMID- 28500888
TI - Impact of furan derivatives and phenolic compounds on hydrogen production from
organic fraction of municipal solid waste using co-culture of Enterobacter
aerogenes and E. coli.
AB - In the present study, the effect of furan derivatives (furfural and 5
hydroxymethylfurfural) and phenolic compounds (vanillin and syringaldehyde) on
hydrogen production from organic fraction of municipal solid waste (OFMSW) was
investigated using co-culture of facultative anaerobes Enterobacter aerogenes and
E. coli. The inhibitors were applied in the concentration ranges of 0.25, 0.5, 1,
2 and 5g/L each. Inhibition coefficients of phenolic compounds were higher than
those of furan derivatives and vanillin exhibited maximum inhibition coefficients
correspondingly lowest hydrogen yield among all inhibitors. Furfural and 5
hydroxymethylfurfural addition resulted in an average decrease of 26.99% and
37.16% in hydrogen yield respectively, while vanillin and syringaldehyde resulted
in 49.40% and 42.26% average decrease in hydrogen yield respectively. Further
analysis revealed that Furfural and 5-hydroxymethylfurfural were completely
degraded up to concentrations of 1g/L, while vanillin and syringaldehyde were
degraded completely up to the concentration of 0.5g/L. Volatile fatty acid
generation decreased with inhibitors addition.
PMID- 28500889
TI - Ammonium stimulates nitrate reduction during simultaneous nitrification and
denitrification process by Arthrobacter arilaitensis Y-10.
AB - The ability of Arthrobacter arilaitensis Y-10 for nitrogen removal from simulated
wastewater was studied. Results showed that ammonium was the best inorganic
nitrogen for strain Y-10's cell growth, which could also promote nitrate
reduction. Approximately 100.0% of ammonium was removed in the nitrogen removal
experiments. The nitrate removal efficiency was 73.3% with nitrate as sole
nitrogen source, and then the nitrate efficiency was increased to 85.3% and
100.0% with ammonium and nitrate (both about 5 or 100mg/L) as the mixed nitrogen
sources. Nitrite accumulation was observed in presence of ammonium and nitrate.
When the concentration of sole nitrite nitrogen was 10.31mg/L, the nitrite
removal efficiency was 100.0%. Neither ammonium nor nitrate was accumulated
during the whole experimental process. All experimental results indicated that A.
arilaitensis Y-10 could remove ammonium, nitrate and nitrite at 15 degrees C from
wastewater, and could also perform simultaneous nitrification and denitrification
under aerobic condition.
PMID- 28500890
TI - Effect of static magnetic field on trichloroethylene removal in a biotrickling
filter.
AB - A laboratory-scale biotrickling filter combined with a magnetic field (MF-BTF)
and a single BTF (S-BTF) were set up to treat trichloroethylene (TCE) gas. The
influences of phenol alone and NaAc-phenol as co-substrates and different MF
intensities were investigated. At low MF intensity, MF-BTF displayed better
performance with 0.20g/L of phenol, 53.6-337.1mg/m3 of TCE, and empty bed
residence times of 202.5s. The performances followed the order MF-BTF (60.0mT)>MF
BTF (30.0mT)>S-BTF (0mT)>MF-BTF (130.0mT), and the removal efficiencies (REs) and
maximum elimination capacities (ECs) corresponded to: 92.2%-45.5%, 2656.8mg/m3h;
89.8%-37.2%, 2169.1mg/m3h; 89.8%-29.8%, 1967.7mg/m3h; 76.0%-20.8%, 1697.1mg/m3h,
respectively. High-throughput sequencing indicated that the bacterial diversity
was lower, whereas the relative abundances of Acinetobacter, Chryseobacterium,
and Acidovorax were higher in MF-BTF. Results confirmed that a proper MF could
improve TCE removal performance in BTF.
PMID- 28500891
TI - Steam-exploded biomass saccharification is predominately affected by
lignocellulose porosity and largely enhanced by Tween-80 in Miscanthus.
AB - In this study, total ten Miscanthus accessions exhibited diverse cell wall
compositions, leading to largely varied hexoses yields at 17%-40% (% cellulose)
released from direct enzymatic hydrolysis of steam-exploded (SE) residues.
Further supplied with 2% Tween-80 into the enzymatic digestion, the Mis7
accession showed the higher hexose yield by 14.8-fold than that of raw material,
whereas the Mis10 had the highest hexoses yield at 77% among ten Miscanthus
accessions. Significantly, this study identified four wall polymer features that
negatively affect biomass saccharification as p<0.05 or 0.01 in the SE residues,
including cellulose DP, Xyl and Ara of hemicellulose, and S-monomer of lignin.
Based on Simons' stain, the SE porosity (defined by DY/DB) was examined to be the
unique positive factor on biomass enzymatic digestion. Hence, this study provides
the potential strategy to enhance biomass saccharification using optimal biomass
process technology and related genetic breeding in Miscanthus and beyond.
PMID- 28500892
TI - Enrichment of extremophilic exoelectrogens in microbial electrolysis cells using
Red Sea brine pools as inocula.
AB - Applying microbial electrochemical technologies for the treatment of highly
saline or thermophilic solutions is challenging due to the lack of proper inocula
to enrich for efficient exoelectrogens. Brine pools from three different
locations (Valdivia, Atlantis II and Kebrit) in the Red Sea were investigated as
potential inocula sources for enriching exoelectrogens in microbial electrolysis
cells (MECs) under thermophilic (70 degrees C) and hypersaline (25% salinity)
conditions. Of these, only the Valdivia brine pool produced high and consistent
current 6.8+/-2.1A/m2-anode in MECs operated at a set anode potential of +0.2V
vs. Ag/AgCl (+0.405V vs. standard hydrogen electrode). These results show that
exoelectrogens are present in these extreme environments and can be used to
startup MEC under thermophilic and hypersaline conditions. Bacteroides was
enriched on the anode of the Valdivia MEC, but it was not detected in the open
circuit voltage reactor seeded with the Valdivia brine pool.
PMID- 28500893
TI - Glucagon receptor knockout mice are protected against acute olanzapine-induced
hyperglycemia.
AB - OBJECTIVES: To determine if glucagon is involved in mediating the increase in
blood glucose levels caused by the second-generation antipsychotic drug
olanzapine. MATERIALS AND METHODS: Whole body glucagon receptor deficient mice
(Gcgr-/-) or WT littermate controls were injected with olanzapine (5mg/kg BW IP)
and changes in blood glucose measured over the following 120min. Separate cohorts
of mice were treated with olanzapine and changes in pyruvate tolerance, insulin
tolerance and whole body substrate oxidation were determined. RESULTS: Olanzapine
treatment increased serum glucagon and lead to rapid increases in blood glucose
concentrations in WT mice. Gcgr-/- mice were protected against olanzapine-induced
increases in blood glucose but this was not explained by differences in terminal
serum insulin concentrations, enhanced AKT phosphorylation in skeletal muscle,
adipose tissue or liver or differences in RER. In both genotypes olanzapine
induced an equivalent degree of insulin resistance as measured using an insulin
tolerance test. Olanzapine treatment led to an exaggerated glucose response to a
pyruvate challenge in WT but not Gcgr-/- mice and this was paralleled by
reductions in the protein content of PEPCK and G6Pase in livers from Gcgr-/-
mice. CONCLUSIONS: Gcgr-/- mice are protected against olanzapine-induced
increases in blood glucose. This is likely a result of reductions in liver
glucose output, perhaps secondary to decreases in PEPCK and G6Pase protein
content. Our findings highlight the central role of the liver in mediating
olanzapine-induced disturbances in glucose homeostasis.
PMID- 28500894
TI - Mercury induced oxidative stress, DNA damage, and activation of antioxidative
system and Hsp70 induction in duckweed (Lemna minor).
AB - Mercury uptake and its effects on physiology, biochemistry and genomic stability
were investigated in Lemna minor after 2 and 6d of exposure to 0-30MUM Hg. The
accumulation of Hg increased in a concentration- and duration-dependent manner,
and was positively correlated with the leaf damage. Oxidative stress after Hg
exposure was evidenced in L. minor by a significant decrease in photosynthetic
pigments, an increase in malondialdehyde and lipoxygenase activities (total
enzyme activity and isoenzymes activity). Fronds of L. minor exposed to Hg showed
an induction of peroxidase, catalase, and ascorbate peroxidase activities (total
enzyme activity and some isoenzymes activities). Exposure of L. minor to Hg
reduced the activity (total enzyme activity and some isoenzymes activities) of
glutathione reductase, and superoxide dismutase. Exposure to Hg produced a
transient increase in the content of glutathione and ascorbic acid. The content
of dehydroascorbate and oxidized glutathione in L. minor were high during the
entire exposure period. Exposure of L. minor to Hg also caused the accumulation
of proline and soluble sugars. The amplification of new bands and the absence of
normal DNA amplicons in treated plants in the random amplified polymorphic DNA
(RAPD) profile indicated that genomic template stability (GTS) was affected by Hg
treatment. The accumulation of Hsp70 indicated the occurrence of a heat shock
response at all Hg concentrations. These results suggest that L. minor plants
were able to cope with Hg toxicity through the activation of various mechanisms
involving enzymatic and non-enzymatic antioxidants, up-regulation of proline, and
induction of Hsp70.
PMID- 28500895
TI - A universal multilingual weightless neural network tagger via quantitative
linguistics.
AB - In the last decade, given the availability of corpora in several distinct
languages, research on multilingual part-of-speech tagging started to grow.
Amongst the novelties there is mWANN-Tagger (multilingual weightless artificial
neural network tagger), a weightless neural part-of-speech tagger capable of
being used for mostly-suffix-oriented languages. The tagger was subjected to
corpora in eight languages of quite distinct natures and had a remarkable
accuracy with very low sample deviation in every one of them, indicating the
robustness of weightless neural systems for part-of-speech tagging tasks.
However, mWANN-Tagger needed to be tuned for every new corpus, since each one
required a different parameter configuration. For mWANN-Tagger to be truly
multilingual, it should be usable for any new language with no need of parameter
tuning. This article proposes a study that aims to find a relation between the
lexical diversity of a language and the parameter configuration that would
produce the best performing mWANN-Tagger instance. Preliminary analyses suggested
that a single parameter configuration may be applied to the eight aforementioned
languages. The mWANN-Tagger instance produced by this configuration was as
accurate as the language-dependent ones obtained through tuning. Afterwards, the
weightless neural tagger was further subjected to new corpora in languages that
range from very isolating to polysynthetic ones. The best performing instances of
mWANN-Tagger are again the ones produced by the universal parameter
configuration. Hence, mWANN-Tagger can be applied to new corpora with no need of
parameter tuning, making it a universal multilingual part-of-speech tagger.
Further experiments with Universal Dependencies treebanks reveal that mWANN
Tagger may be extended and that it has potential to outperform most state-of-the
art part-of-speech taggers if better word representations are provided.
PMID- 28500897
TI - Genetic alterations within TLR genes in development of Toxoplasma gondii
infection among Polish pregnant women.
AB - PURPOSE: The research was conducted to evaluate the role of genotypes, haplotypes
and multiple-SNP variants in the range of TLR2, TLR4 and TLR9 single nucleotide
polymorphisms (SNPs) in the development of Toxoplasma gondii infection among
Polish pregnant women. MATERIAL AND METHODS: The study was performed for 116
Polish pregnant women, including 51 patients infected with T. gondii, and 65 age
matched control pregnant individuals. Genotypes in TLR2 2258 G>A, TLR4 896 A>G,
TLR4 1196 C>T and TLR9 2848 G>A SNPs were estimated by self-designed, nested PCR
RFLP assays. Randomly selected PCR products, representative for distinct
genotypes in the studied polymorphisms, were confirmed by sequencing. All the
genotypes were calculated for Hardy-Weinberg (H-W) equilibrium and TLR4 variants
were tested for linkage disequilibrium. Relationships were assessed between
alleles, genotypes, haplotypes or multiple-SNP variants in TLR polymorphisms and
the occurrence of T. gondii infection in pregnant women, using a logistic
regression model. RESULTS: All the analyzed genotypes preserved the H-W
equilibrium among the studied groups of patients (P>0.050). Similar distribution
of distinct alleles and individual genotypes in TLR SNPs, as well as of
haplotypes in TLR4 polymorphisms, were observed in T. gondii infected and control
uninfected pregnant women. However, the GACG multiple-SNP variant, within the
range of all the four studied polymorphisms, was correlated with a decreased risk
of the parasitic infection (OR 0.52, 95% CI 0.28-0.97; P<=0.050). CONCLUSIONS:
The polymorphisms, located within TLR2, TLR4 and TLR9 genes, may be involved
together in occurrence of T. gondii infection among Polish pregnant women.
PMID- 28500896
TI - A MicroRNA/Ubiquitin Ligase Feedback Loop Regulates Slug-Mediated Invasion in
Breast Cancer.
AB - The transformation of a normal cell to cancer requires the derail of multiple
pathways. Normal signaling in a cell is regulated at multiple stages by the
presence of feedback loops, calibration of levels of proteins by their regulated
turnover, and posttranscriptional regulation, to name a few. The tumor suppressor
protein FBXO31 is a component of the SCF E3 ubiquitin ligase and is required to
arrest cells at G1 following genotoxic stresses. Due to its growth-suppression
activity, it is underexpressed in many cancers. However, the molecular mechanism
underlying the translational regulation of FBXO31 remains unclear. Here we show
that the oncogenic microRNAs miR-93 and miR-106a repress FBXO31, resulting in the
upregulation of Slug, which is involved in epithelial-mesenchymal transition and
cell invasion. FBXO31 targets and ubiquitylates Slug for proteasomal degradation.
However, this mechanism is repressed in breast tumors where miR-93 and miR-106a
are overexpressed. Our study further unravels an interesting mechanism whereby
Slug drives the expression of miR-93 and miR-106a, thus establishing a positive
feedback loop to maintain an invasive phenotype. Together, these results
establish the presence of interplay between microRNAs and the ubiquitination
machinery, which together regulate cancer cell invasion.
PMID- 28500898
TI - The fact not to ignore: Mean blood pressure is the main predictor of increased
arterial stiffness in patients with systemic rheumatic diseases.
AB - PURPOSE: We aimed to evaluate the association between carotid-radial pulse wave
velocity (PWV), augmentation index (AIx), and flow-mediated dilatation (FMD) of
the brachial artery and factors potentially influencing them in patients with
rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic
sclerosis (SSc). MATERIAL AND METHODS: 316 patients diagnosed with RA (32%), SLE
(20%), SSc (16%) and 156 controls (32%) were included in the study. Parameters of
arterial stiffness AIx and PWV were obtained using applanation tonometry. FMD
reflecting endothelial function was measured by ultrasound. RESULTS: AIx was
increased in all three diseases (p<0.0001), but no differences were found between
rheumatic diseases. In most of the RA cases PWV values were abnormal (on average
by 0.52m/sec higher than in controls), while in SSc patients FMD values were
diminished (p=0.006). Mean blood pressure (MBP) was the most consistent
predictive factor in all three diseases, influencing both PWV and AIx, although
patient age was also important in variation of AIx. The disease activity score
(DAS28) was relevant only in RA patients. Furthermore, SLE disease activity index
in SLE or Rodnan skin thickness score had no statistical significance in SSc and
inflammatory markers. CONCLUSIONS: Both, PWV and AIx are dependent on MBP and age
DAS28 may affect AIx in RA patients, while other disease or inflammatory markers
are unlikely to have any effect. MBP is one of the main cardiovascular risk
factors affecting the arterial stiffness in RA, SLE and SSc patients therefore
controlling MBP in systemic rheumatic disease patients is mandatory.
PMID- 28500899
TI - Hysteroscopy in the treatment of uterine cesarean section scar diverticulum: A
systematic review.
AB - The aim of this paper is to review and to analyze the results of previous studies
dealing with hysteroscopic treatment of postcesarean scar defects. A systematic
review of publications indexed in MEDLINE/PubMed database identified a total of
11 studies dealing with resectoscopic treatment of postcesarean scar defect. The
review was conducted in line with the Meta-analysis of Observational Studies in
Epidemiology (MOOSE) guidelines and the PRISMA statement. In only few studies,
patients were qualified for hysteroscopic surgery based on the measurement of the
defect depth and thickness of residual myometrium above the pouch. Two principal
techniques were used for the hysteroscopic treatment: resection of one edge of
the scar diverticulum, and resection of the inferior and superior edges of the
defect. Additionally, most authors performed electrocauterization of the niche
bottom. Resectoscopic treatment turned out to be highly effective in the case of
women with AUB. No complications of the hysteroscopic procedure have been
reported. Methodological value of the reviewed studies was relatively low due to
non-unified selection/verification criteria and incomplete, non-systematic
postoperative assessment. In conclusion, hysteroscopic treatment seems to be a
promising option in the management of postcesarean scar defects, but still
further research is needed on the problem in question.
PMID- 28500900
TI - Treatment of refractory epilepsy patients with autologous mesenchymal stem cells
reduces seizure frequency: An open label study.
AB - PURPOSE: Existing anti-epileptic drugs (AED) have limited efficiency in many
patients, necessitating the search for alternative approaches such as stem cell
therapy. We report the use of autologous patient-derived mesenchymal stem cells
(MSC) as a therapeutic agent in symptomatic drug-resistant epilepsy in a Phase I
open label clinical trial (registered as NCT02497443). PATIENTS AND METHODS: The
patients received either standard treatment with AED (control group), or AED
supplemented with single intravenous administration of undifferentiated
autologous MSC (target dose of 1*106cells/kg), followed by a single intrathecal
injection of neurally induced autologous MSC (target dose of 0.1*106cells/kg).
RESULTS: MSC injections were well tolerated and did not cause any severe adverse
effects. Seizure frequency was designated as the main outcome and evaluated at 1
year time point. 3 out of 10 patients in MSC therapy group achieved remission (no
seizures for one year and more), and 5 additional patients became responders to
AEDs, while only 2 out of 12 patients became responders in control group
(difference significant, P=0.0135). CONCLUSIONS: MSC possess unique
immunomodulatory properties and are a safe and promising candidate for cell
therapy in AED resistant epilepsy patients.
PMID- 28500901
TI - The course of cancer related fatigue up to ten years in early breast cancer
patients: What impact in clinical practice?
AB - Little is known about the cancer related fatigue (CRF) along cancer course and
risk factors that could predict CRF development and persistence in breast cancer
(BC) survivors. This prospective study detected incidence, timing of onset,
duration of CRF, impact on QoL and psychological distress. Seventy-eight early BC
patients, undergoing chemotherapy (CT) followed or not by hormonal therapy were
assessed for QoL and psychological distress by EORTC QLQC30 and HADs
questionnaires. Fatigue was investigated with mix methods, structured interview
and psychometric measures. A qualitative analysis was added to assess the
behavioral pattern of CRF. Low fatigue levels were identified after surgery (9%),
increasing during (49%) and at the end of CT (47%), maintaining after 1 year
(31%) and declining up to ten years of follow-up. Prevalence of CRF was higher at
the end of CT and lower at follow-up. At the end and after 1 and 2 years from CT,
persistence of CRF was associated to anxiety in 20%, 11% and 5% and to depression
in 15%, 10% and 5% respectively. A relationship between CRF and psychological
distress was observed; patients presenting depression and anxiety before CT were
at higher risk for fatigue onset at a later period. A relationship between
fatigue and QoL was noted at the end of CT. Our study shows the fatigue timely
trend in early BC patients from surgery, CT and follow-up. Identification of
biological, psychological, social predictor factors related to fatigue could be
helpful for early interventions in patients at higher risk of developing fatigue.
PMID- 28500902
TI - RNA-sequencing and pathway analysis reveal alteration of hepatic steroid
biosynthesis and retinol metabolism by tributyltin exposure in male rare minnow
(Gobiocypris rarus).
AB - Tributyltin (TBT) is widely spread in aquatic ecosystems. Although adverse
effects of TBT on reproduction and lipogenesis are observed in fishes, the
underlying mechanisms, especially in livers, are still scarce and inconclusive.
Thus, RNA-sequencing runs were performed on the hepatic libraries of adult male
rare minnow (Gobiocypris rarus) after TBT exposure for 60d. After differentially
expressed genes were identified, enrichment analysis and validation by
quantitative real-time PCR were conducted. The results showed that TBT up
regulated the profile of hepatic genes in the steroid biosynthesis pathway and
down-regulated the profile of hepatic genes in the retinol metabolism pathway. In
the hepatic steroid biosynthesis pathway, TBT might induce biosynthesis of
cholesterol, which could affect the bioavailability of steroid hormones. More
important, 3beta-hydroxysteroid 3-dehydrogenase, a key enzyme in the biosynthesis
of all active steroid hormones, was up-regulated by TBT exposure. In the hepatic
retinol metabolism pathway, TBT impaired retinoic acid homeostasis which plays
essential roles in both reproduction and lipogenesis. The results of two pathways
offered new mechanisms underlying the toxicology of TBT and represented a
starting point from which detailed mechanistic links should be explored.
PMID- 28500904
TI - Endometrial adenocarcinoma recurrence presenting with tibial metastasis: Report
of a case.
AB - INTRODUCTION: Metastatic bone disease at extremities is mostly associated with
lung, liver, prostat, thyriod or breast malignancies. There for surgeons
generally tends to seek for a primary tumor originating from these organs. Herein
a case of endometrial adenocarcinoma recurrence that presented with symptoms of
tibial pain is described. PRESENTATION OF CASE: 59 year-old woman was admitted to
our orthopaedic oncology unit with pain, swelling and tenderness at right cruris
for two weeks without any trauma history. Her medical history revealed that she
had a total abdominal hysterectomy and bilateral salpingo-oophorectomy. During
follow-ups no recurrence had been detected. Initial X-rays of the right tibia
showed a lytic and expansile mass located at the shaft of the tibia suggesting
metastasis. A wide resection of the lesion with clear margins was performed two
weeks after first admittance. Resected area was replaced by fresh frozen femoral
shaft allograft. At postoperative 17th month. X-rays obtained at last follow-up
demostrated full healing and integration of allograft. DISCUSSION: Endometrial
adenocarcinoma is a disease of postmenapousal women with 95% of the cases
occurring after the age of 40 years. Patients with advanced or recurrent
endometrial cancer often have distant metastases found within the lymph nodes,
liver, and/or lung. CONCLUSION: Recurrence of endometrial cancer as a solitary
bone lesion is a rare situation. Wide resection and reconstruction with an
allograft or an intercalar prosthesis might be an option to increase survival and
possible cure of the patient.
PMID- 28500905
TI - Double acousto-optic deflector system for increased scanning range of laser
beams.
AB - A new laser scanning system is presented based on two wide-band acousto-optic
deflectors. The interaction medium is tellurium dioxide. Anisotropic interactions
take place under two different tangential phase matching configurations in such a
way that the acousto-optic bandwidths add up. We demonstrate the feasibility of
such a cascade deflection system for the wavelength of lambda=514nm. The total
frequency bandwidth is Deltaf=100MHz, equally distributed between the two acousto
optic deflectors. The total angular scan at the output is Deltatheta=4.4 degrees
leading to 125 resolvable spots for a 1mm truncated Gaussian beam.
PMID- 28500903
TI - Microcystin-LR bioconcentration induces antioxidant responses in the digestive
gland of two marine bivalves Crassostrea gigas and Mytilus edulis.
AB - Microcystins (MCs) are a major group of potent cyanobacterial toxins found in
freshwater and even brackish waterbodies. To understand the putative correlation
between bioconcentration of MCs and antioxidant responses of the digestive gland
of bivalves, Pacific oyster Crassostrea gigas and blue mussel Mytilus edulis were
exposed to different concentrations (0.1, 1, 10 and 20MUgL-1) of MC-Leucine
Arginine (LR) for seven days. MC-LR bioconcentrated in the digestive glands of
both bivalves during exposure period. The levels were slightly reduced when the
bivalves were exposed to seawater during depuration (7days), while approximately
0.1MUgL-1 of MC-LR was observed in the 10 and 20MUgL-1 exposed bivalves at the
end of depuration. Intracellular malondialdehyde (MDA) and glutathione (GSH)
levels were significantly elevated in the 10 and 20MUgL-1 exposed bivalves at
7day, and the levels were maintained during depuration in both bivalves. Overall,
significant higher levels of enzymatic activities of antioxidant defense systems
such as glutathione S-transferase (GST), catalase (CAT), superoxide dismutase
(SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) were observed
in the 10 and 20MUgL-1 exposed bivalves. Interestingly, most of higher levels of
Pacific oyster were detected at exposure period, while blue mussel showed higher
levels at depuration phase, suggesting a species-specific sensitivity upon MC-LR.
These patterns were correlated with the bioconcentration patterns of MC-LR as
Pacific oyster was highly accumulated by MC-LR during exposure period, but blue
mussel showed prolonged high levels of MC-LR for depuration phase. Our results
will be useful to understand species-specific bioconcentration of MC-LR in
bivalves and their effects on intracellular oxidative status via accumulation.
PMID- 28500906
TI - Feasibility and reliability of a mobile tool to evaluate exposure to tobacco
product marketing and messages using ecological momentary assessment.
AB - INTRODUCTION: Existing measures of tobacco marketing and messaging exposure are
limited, relying on recall, recognition, or proxy measures. This study aimed to
determine the feasibility and reliability of a mobile application for the
measurement of tobacco and e-cigarette marketing and message exposure using
ecological momentary assessment (EMA). METHODS: Young adults from Austin, TX
(n=181, ages 18-29) were instructed to use a mobile application to record all
sightings of marketing or social media related to tobacco (including e
cigarettes) in real-time for 28days (Event EMAs). Tobacco product use and recall
of message encounters were assessed daily using an app-initiated EMA (Daily
EMAs). RESULTS: The mobile app was a feasible and acceptable method to measure
exposure to tobacco messages. The majority of messages (45.0%) were seen on the
Internet, and many were user-generated. Thirty-day recall of messages at baseline
was poorly correlated with messages reported via Event EMA during the study
period; however, the correlation between post-study 30-day recall and Event EMA
was much stronger (r=0.603 for industry-sponsored messages, r=0.599 for user
generated messages). Correlations between Daily EMAs and 30-day recall of message
exposure (baseline and post-study) were small (baseline: r=0.329-0.389) to large
(post-study: r=0.656-0.766). CONCLUSIONS: These findings suggest that EMA is a
feasible and reliable method for measuring tobacco message exposure, especially
given the prevalence of messages encountered online and on social media. Recall
measures are limited in their ability to accurately represent marketing exposure,
but might be improved by a period of priming or clearer response categories.
PMID- 28500907
TI - In the process of drinking to cope among college students: An examination of
specific vs. global coping motives for depression and anxiety symptoms.
AB - The present study sought to address an issue in the drinking to cope (DTC)
motives literature, namely the inconsistent application of treating DTC motives
as a single construct and splitting it into DTC-depression and DTC-anxiety
motives. Specifically, we aimed to determine if the effects of anxiety and
depression on alcohol-related problems are best explained via their associations
with DTC with specific affects or via their associations with a more global
measure of DTC by testing four distinct models: the effects of anxiety/depression
on alcohol-related problems mediated by DTC-anxiety only (Model 1), these effects
mediated by DTC-depression only (Model 2), these effects mediated by a combined,
global DTC factor (Model 3), and these effects mediated by both DTC-anxiety and
DTC-depression (Model 4). Using path analysis/structural equation modeling across
two independent samples, we found that there was a significant total indirect
effect of both anxiety and depressive symptoms on alcohol-related problems in
every model. However, there was a slightly larger indirect effect in all models
using the global DTC motives factor compared to even the model that included the
two distinct DTC motives. Our results provide some preliminary evidence that at
least at the between-subjects level, a global DTC motives factor may have more
predictive validity than separate DTC motives. Additional research is needed to
examine how to best operationalize DTC motives at different levels of analysis
(e.g., within-subjects vs. between subjects) and in different populations (e.g.,
college students vs. individuals with alcohol use disorder).
PMID- 28500908
TI - Distress tolerance interacts with circumstances, motivation, and readiness to
predict substance abuse treatment retention.
AB - BACKGROUND: Our understanding of the conditions that influence substance abuse
treatment retention in urban African American substance users is limited. This
study examined the interacting effect of circumstances, motivation, and readiness
(CMR) with distress tolerance to predict substance abuse treatment retention in a
sample of urban African American treatment-seeking substance users. METHODS: Data
were collected from 81 African American substance users entering residential
substance abuse treatment facility in an urban setting. Participants completed
self-reported measures on CMR and distress tolerance. In addition, participants
were assessed on psychiatric comorbidities, substance use severity, number of
previous treatments, and demographic characteristics. Data on substance abuse
treatment retention were obtained using administrative records of the treatment
center. RESULTS: Logistic regression analysis found that the interaction of CMR
and distress tolerance was significant in predicting substance abuse treatment
retention. Higher score on CMR was significantly associated with increased
likelihood of treatment retention in substance users with higher distress
tolerance, but not in substance users with lower distress tolerance. CONCLUSIONS:
Findings of the study indicate that at higher level of distress tolerance,
favorable external circumstances, higher internal motivation, and greater
readiness to treatment are important indicators of substance abuse treatment
retention. The study highlights the need for assessing CMR and distress tolerance
levels among substance users entering treatment, and providing targeted
interventions to increase substance abuse treatment retention and subsequent
recovery from substance abuse among urban African American substance users.
PMID- 28500909
TI - Development and testing of a moment-based coactivation index to assess complex
dynamic tasks for the lumbar spine.
AB - BACKGROUND: Many methods exist to describe coactivation between muscles. However,
most methods have limited capability in the assessment of coactivation during
complex dynamic tasks for multi-muscle systems such as the lumbar spine. The
ability to assess coactivation is important for the understanding of
neuromuscular inefficiency. In the context of this manuscript, inefficiency is
defined as the effort or level of coactivation beyond what may be necessary to
accomplish a task (e.g., muscle guarding during postural stabilization). The
objectives of this study were to describe the development of an index to assess
coactivity for the lumbar spine and test its ability to differentiate between
various complex dynamic tasks. METHODS: The development of the coactivation index
involved the continuous agonist/antagonist classification of moment contributions
for the power-producing muscles of the torso. Different tasks were employed to
test the range of the index including lifting, pushing, and Valsalva. FINDINGS:
The index appeared to be sensitive to conditions where higher coactivation would
be expected. These conditions of higher coactivation included tasks involving
higher degrees of control. Precision placement tasks required about 20% more
coactivation than tasks not requiring precision, lifting at chest height required
approximately twice the coactivation as mid-thigh height, and pushing fast speeds
with turning also required at least twice the level of coactivity as slow or
preferred speeds. INTERPRETATION: Overall, this novel coactivation index could be
utilized to describe the neuromuscular effort in the lumbar spine for tasks
requiring different degrees of postural control.
PMID- 28500910
TI - Ankle strength impairments associated with knee osteoarthritis.
AB - BACKGROUND: Knee Osteoarthritis seems to negatively impact ankle biomechanics.
However, the effect of knee osteoarthritis on ankle muscle strength has not been
clearly established. This study aimed to evaluate the ankle strength of the
plantar flexors and dorsiflexors of patients with knee osteoarthritis in
different degrees of severity. METHODS: Thirty-seven patients with knee
osteoarthritis and 15 controls, subjected to clinical and radiographic analysis,
were divided into three groups: control, mild, and moderate knee osteoarthritis.
Participants answered a self-reported questionnaire and accomplished a muscle
torque assessment of the ankle using the Biodex dynamometer in isometric,
concentric and eccentric modes. FINDINGS: The mild osteoarthritis group (peak
torque=26.85(SD 3.58)) was significantly weaker than the control (peak
torque=41.75(SD 4.42)) in concentric plantar flexion (P<0.05). The control and
mild osteoarthritis groups were not significantly different from the moderate
osteoarthritis group (peak torque=36.12(SD 4.61)) in concentric plantar flexion.
There were no significant differences for dorsiflexion among the groups; however
the control and moderate osteoarthritis groups presented large and medium
standardized mean differences. The mild osteoarthritis group was significantly
lower than the control and moderate osteoarthritis groups in the concentric
plantar flexion by concentric dorsiflexion torque ratio. INTERPRETATION: Ankle
function exhibited impairments in patients with knee osteoarthritis, especially
in the plantar flexion torque, in which the mild osteoarthritis group was weaker
than the control. Interestingly, patients with moderate knee osteoarthritis
showed results similar to the control group in plantar flexion torque. The
results raise the possibility of a compensatory mechanism of the plantar flexors
developed by patients in more advanced degrees to balance other muscle failures.
PMID- 28500911
TI - Do welfare regimes matter for oral health? A multilevel analysis of European
countries.
AB - While the role of political factors on population health has recently received
increasing attention, relatively little is known in that respect for oral health.
We aimed to assess the influence of welfare state regimes on the variation in
adult oral health between European countries, building on the existing literature
by using a multilevel approach. Our analysis also explored how the oral health of
people with different socioeconomic position was influenced by living in five
different welfare state regimes. We analysed data from the Eurobarometer survey
2009. The main outcome was no functional dentition, defined as having fewer than
20 natural teeth. Age, gender, marital status, education and occupational social
class were the individual-level explanatory variables, while welfare regimes, GDP
per capita and GDP annual growth were the country-level variables. Multilevel
logistic regression models were fitted with individuals nested within countries.
Results revealed that country-level characteristics accounted for 8.1% of the
variation in oral health. Adults in all welfare regimes were more likely to have
poorer oral health than their counterparts in the Scandinavian regime, with those
in Eastern countries being 6.94 (95% CI: 3.62-12.67) times as likely to lack a
functional dentition as adults in Scandinavian countries. The variation at
country-level reduced significantly when welfare regimes were introduced into the
model (from 0.57 to 0.16; 72% reduction), indicating that welfare regime
explained much of the variation in the outcome among European countries. Finally,
adults with less education and lower occupational level were more likely to have
no functional dentition, especially in the Eastern and Bismarckian welfare
regimes.
PMID- 28500912
TI - Clotting time-dependent pseudohyperkalemia associated with Sezary syndrome.
PMID- 28500914
TI - Limitations of experiments performed in artificially made OECD standard soils for
predicting cadmium, lead and zinc toxicity towards organisms living in natural
soils.
AB - Development of comparative toxicity potentials of cationic metals in soils for
applications in hazard ranking and toxic impact assessment is currently
jeopardized by the availability of experimental effect data. To compensate for
this deficiency, data retrieved from experiments carried out in standardized
artificial soils, like OECD soils, could potentially be tapped as a source of
effect data. It is, however, unknown whether such data are applicable to natural
soils where the variability in pore water concentrations of dissolved base
cations is large, and where mass transfer limitations of metal uptake can occur.
Here, free ion activity models (FIAM) and empirical regression models (ERM, with
pH as a predictor) were derived from total metal EC50 values (concentration with
effects in 50% of individuals) using speciation for experiments performed in
artificial OECD soils measuring ecotoxicological endpoints for terrestrial
earthworms, potworms, and springtails. The models were validated by predicting
total metal based EC50 values using backward speciation employing an independent
set of natural soils with missing information about ionic composition of pore
water, as retrieved from a literature review. ERMs performed better than FIAMs.
Pearson's r for log10-transformed total metal based EC50s values (ERM) ranged
from 0.25 to 0.74, suggesting a general correlation between predicted and
measured values. Yet, root-mean-square-error (RMSE) ranged from 0.16 to 0.87 and
was either smaller or comparable with the variability of measured EC50 values,
suggesting modest performance. This modest performance was mainly due to the
omission of pore water concentrations of base cations during model development
and their validation, as verified by comparisons with predictions of published
terrestrial biotic ligand models. Thus, the usefulness of data from artificial
OECD soils for global-scale assessment of terrestrial ecotoxic impacts of Cd, Pb
and Zn in soils is limited due to relatively small variability of pore water
concentrations of dissolved base cations in OECD soils, preventing their
inclusion in development of predictive models. Our findings stress the importance
of considering differences in ionic composition of soil pore water when
characterizing terrestrial ecotoxicity of cationic metals in natural soils.
PMID- 28500915
TI - A comparison of denitrifying bacterial community structures and abundance in
acidic soils between natural forest and re-vegetated forest of Nanling Nature
Reserve in southern China.
AB - Denitrification plays a key role in converting reactive nitrogen species to
dinitrogen gas back into the atmosphere to maintain the equilibrium of nitrogen
cycling in ecosystems. In this study, functional genes of nirK and nosZ were used
to detect the community structure and abundance of denitrifying microorganisms in
acidic forest soils in southern China. Three sets of factors were considered for
a comparison among 5 forests, including forest types (natural vs. re-vegetated),
depths (surface layer vs. lower layer) and seasons (winter vs. summer). The
community of nirK gene detected from these acidic forest soils was closely
related to Proteobacteria especially alpha-Proteobacteria and uncultured soil
sequences, while that of nosZ gene was affiliated with the alpha-, beta- and
gamma-Proteobacteria. Higher diversity of denitrifiers was observed in re
vegetated forest soils than natural ones. Not only the community but also the
abundance showed significant differences between forest types as well as depths.
The abundance of denitrifiers ranged from 105 to 107 gene copies g-1 dry soil in
this study. For nirK gene, the abundance was much higher in the lower layer than
surface layer in both forest types, and the differences between winter and summer
in natural forest soils were higher than those in re-vegetated forest soils. The
abundance of nosZ and nirK genes showed a similar trend in natural forest, but
the former was higher in matured forest than re-vegetated forest. This study
provided a direct comparison on community composition and abundance of
denitrifying bacteria in natural and re-vegetated acidic forest soils to allow
further assessment of the nitrogen cycling.
PMID- 28500916
TI - Valuing urban open space using the travel-cost method and the implications of
measurement error.
AB - Urbanization has placed pressure on open space within and adjacent to cities. In
recent decades, a greater awareness has developed to the fact that individuals
derive multiple benefits from urban open space. Given the location, there is
often a high opportunity cost to preserving urban open space, thus it is
important for both public and private stakeholders to justify such investments.
The goals of this study are twofold. First, we use detailed surveys and precise,
accessible, mapping methods to demonstrate how travel-cost methods can be applied
to the valuation of urban open space. Second, we assess the degree to which
typical methods of estimating travel times, and thus travel costs, introduce bias
to the estimates of welfare. The site we study is Taylor Mountain Regional Park,
a 1100-acre space located immediately adjacent to Santa Rosa, California, which
is the largest city (~170,000 population) in Sonoma County and lies 50 miles
north of San Francisco. We estimate that the average per trip access value
(consumer surplus) is $13.70. We also demonstrate that typical methods of
measuring travel costs significantly understate these welfare measures. Our study
provides policy-relevant results and highlights the sensitivity of urban open
space travel-cost studies to bias stemming from travel-cost measurement error.
PMID- 28500913
TI - MYB fusions and CD markers as tools for authentication and purification of cancer
stem cells from salivary adenoid cystic carcinoma.
AB - Cancer stem cells (CSC) are considered the major cause of aggressive tumor
behavior, recurrence, metastases, and resistance to radiation, making them an
attractive therapeutic target. However, isolation of CSC from tumor tissue and
their characterization are challenging due to uncertainty about their molecular
markers and conditions for their propagation. Adenoid cystic carcinoma (ACC),
which arises predominantly in the salivary glands, is a slow-growing but
relentless tumor that frequently invades nerves and metastasizes. New effective
treatment approaches for ACC have not emerged over the last 40years. Previously,
based on a highly conserved SOX10 gene signature that we identified in the
majority of ACC tumors, we suggested the existence in ACC of SOX10+ cells with
neural stem properties and corroborated this hypothesis via isolation from ACC
tissue a novel population of CSC, termed ACC-CSC. These cells activated NOTCH1
signaling and co-expressed SOX10 and other ACC-intrinsic neural crest stem cell
markers with CD133, a CSC cell surface marker, suggesting that ACC is driven by a
previously uncharacterized population of SOX10+/CD133+ cells with neural stem
cell properties. Here, we authenticated ACC identity of our primary cultures by
demonstrating that most of them harbor MYB-NFIB fusions, which are found in 86%
of ACC. We demonstrated using CyTOF, a novel mass cytometry technology, that
these cells express high beta-catenin and STAT3 levels and are marked by CD24 and
CD44. Finally, to streamline development of ACC cell lines, we developed RT-PCR
tests for distinguishing mouse and human cells and used immunomagnetic cell
sorting to eliminate mouse cells from long-term cell cultures. Overall, this
study describes a new population of CSC that activates signaling pathways
associated with poor prognosis, validates their ACC identity, and optimizes
approaches that can be used for purification of ACC-CSC and generation of cell
lines.
PMID- 28500917
TI - Using rapid-scan EPR to improve the detection limit of quantitative EPR by more
than one order of magnitude.
AB - X-band rapid-scan EPR was implemented on a commercially available Bruker ELEXSYS
E580 spectrometer. Room temperature rapid-scan and continuous-wave EPR spectra
were recorded for amorphous silicon powder samples. By comparing the resulting
signal intensities the feasibility of performing quantitative rapid-scan EPR is
demonstrated. For different hydrogenated amorphous silicon samples, rapid-scan
EPR results in signal-to-noise improvements by factors between 10 and 50. Rapid
scan EPR is thus capable of improving the detection limit of quantitative EPR by
at least one order of magnitude. In addition, we provide a recipe for setting up
and calibrating a conventional pulsed and continuous-wave EPR spectrometer for
rapid-scan EPR.
PMID- 28500918
TI - Experience using high-dose glucose-insulin-potassium (GIK) in critically ill
patients.
AB - PURPOSE: To audit the use of GIK in terms of safety, haemodynamic effects, and
impact on catecholamine dosage. MATERIALS AND METHODS: A retrospective,
descriptive, evaluative audit of GIK use within the adult ICU of a London
teaching hospital was conducted. Rescue therapy of GIK (up to
1.0Unitsinsulin/kg/h) was administered to improve cardiac function. Outcomes were
ICU survival, change in cardiac index (CI) and blood lactate levels, events of
hypoglycaemia, hyperglycaemia, hypokalaemia and hyperkalaemia, and
discontinuation time of catecholamine inotropes. RESULTS: Of 85 patients treated
with GIK, 13 (15.3%) survived their ICU stay and 9 (10.5%) were discharged home.
In patients surviving until 72h, a trend of improved CI and lactate levels was
seen, often with reductions in catecholamine dosing. Inotropes were discontinued
in 35 (54%) patients. Severe hypoglycaemia (<2mmol/l), hyperglycaemia
(>20mmol/l), hypokalaemia (<2.5mmol/l) and hyperkalaemia (>7mmol/l) during GIK
affected 1, 6, 8 and 1 patients, respectively. These abnormalities were quickly
identified. No measurable harm was noted. CONCLUSIONS: High-dose GIK can be
safely used in critically ill patients, though blood glucose and potassium levels
must be monitored frequently. GIK was associated with improved CI and blood
lactate levels. Impact on survival requires prospective evaluation.
PMID- 28500919
TI - Kinetics of circulating fetuin-A may predict mortality independently from
adiponectin, high molecular weight adiponectin and prognostic factors in
critically ill patients with sepsis: A prospective study.
AB - PURPOSE: Fetuin-A and adiponectin, major hepatokine and adipokine respectively,
have been implicated in systematic inflammation. Our aim was to jointly
investigate whether kinetics of circulating fetuin-A, adiponectin and its isoform
HMWA predict 28-day mortality in sepsis. MATERIALS AND METHODS: In a prospective
study, serum fetuin-A, adiponectin and HMWA were determined in 102 ICU patients
fulfilling the diagnostic criteria of SEPSIS-3, at enrollment and one week after,
and in 102 healthy controls matched on age and gender. RESULTS: Serum fetuin-A
was significantly lower in septic patients than controls (p<0.001). Among septic
patients, those with septic shock and nonsurvivors presented lower fetuin-A, but
higher adiponectin and HMWA compared to patients with sepsis and survivors
respectively, both at baseline and day 7 (p<0.001). Fetuin-A exhibited negative
correlations with APACHE II, CRP, procalcitonin, adiponectin and IL-6 but a
positive one with albumin. Reduced fetuin-A as well as lower serum kinetics of
fetuin-A (HR: 0.55, 95% C.I. 0.34-0.91, p=0.02), adiponectin but not HMWA were
independently associated with 28-day mortality adjusting for age, gender, BMI,
APACHE II, septic shock and laboratory biomarkers. CONCLUSIONS: Circulating
fetuin-A kinetics may be a prognostic biomarker in septic patients. More research
is essential to elucidate fetuin-A's ontological role in sepsis pathophysiology.
PMID- 28500920
TI - The impact of delayed rapid response call activation on patient outcomes.
AB - PURPOSE: To investigate the impact of delay in rapid response call (RRC)
activation on Hospital mortality. MATERIALS AND METHODS: This study was conducted
in a university affiliated hospital providing medical, surgical, mental health,
maternity, and pediatric services. RRCs were considered delayed if RRC activation
was delayed by >=15min. The primary outcome measure was in-hospital mortality.
Secondary outcomes included hospital length of stay (LOS), requirement of ICU
admission, as well as requirement of mechanical ventilation and ICU LOS for
patients requiring ICU admission. RESULTS: A total of 826 RRCs occurred in 629
patient admissions. A quarter of all RRCs were delayed by >=15min, with a median
delay of 1h and 20min. Patients with a delayed RRC had significantly higher in
hospital mortality (34.7% vs. 21.2%; p=0.001,) and significantly longer
hospitalizations (11.6 vs. 8.4days; p=0.036). After adjusting for confounders,
RRC activation was independently associated with increased in-hospital mortality
(OR=1.79; 95% CI=1.17-2.72: p=0.007). CONCLUSIONS: A delay of >=15min was
associated with significantly increased in-hospital mortality and longer
hospitalization. The factors contributing to the observed increase in mortality
with delayed RRCs require further exploration.
PMID- 28500921
TI - Development and validation of two measures of emotional contrast avoidance: The
contrast avoidance questionnaires.
AB - The Contrast Avoidance (CA) model (Newman & Llera, 2011) proposed that
individuals with generalized anxiety disorder (GAD) fear sharp emotional shifts
(or contrasts), such as the shift from a pleasant or neutral state to one of
sudden distress following a negative event. Further, the model suggests that
chronic worry is employed by those with GAD to sustain negative emotionality as a
means to avoid sudden shifts into negativity. The model has received empirical
support; however, no validated measure exists to assess CA tendencies. In this
paper we developed and tested two measures of CA: one focusing on worry, and
another examining broader mechanisms of CA that could be used test whether CA is
applicable to other disorders. In Study 1, Part 1, we used 3 samples of
participants (each N=410) to perform item reduction, exploratory factor analysis,
and confirmatory factor analysis. In Study 1, Part 2, we performed tests of
construct validity. In Study 2, we used a new sample (N=126) to determine test
retest reliability. All data point to the strong psychometric properties of the
CA questionnaires and their relationship to GAD. Both measures distinguished
between participants reporting clinical levels of GAD symptoms and nonanxious
controls, demonstrating their utility as complementary measures of CA tendencies.
PMID- 28500923
TI - History, injury, and psychosocial risk factor commonalities among cases of fatal
and near-fatal physical child abuse.
AB - Failure to recognize child maltreatment results in chronic exposure to high-risk
environments where re-injury or death may occur. We analyzed a series (n=20) of
fatal (n=10) and near-fatal (n=10) physical child abuse cases from the
Commonwealth of Kentucky to identify commonalities and determine whether
indicators of maltreatment were present prior to the child's fatal or near-fatal
event. We conducted retrospective state record reviews involving children <4years
of age classified as physical child abuse by the Cabinet for Health and Family
Services during a 12 month period. Cases were distributed across 17 counties. IRB
approvals were obtained. Three reviewers concurrently abstracted case data from
medical, social, and legal documents, and descriptive statistics were analyzed.
Median age of subjects was 7.5 months (range 1-32 months); 55% were male.
Psychosocial risk factors (PRFs) were present in 100% of cases. Traumatic brain
injury (95%) and bruising (90%) were the most common injuries. Of the 14 children
with available prior medical records, 9 (64%) had sentinel injuries in the form
of prior unexplained bruising; all nine suffered subsequent traumatic brain
injury resulting in four deaths. A male was caring for the child at the time of
the final event in 70% of cases. Our study identified key commonalities across
cases of fatal and near-fatal abuse, highlighting the prevalence of psychosocial
risk factors and the significance of prior unexplained bruising as a herald of
escalating abuse. Further study is warranted to ascertain the predictive value of
our findings in the larger population.
PMID- 28500922
TI - Adverse childhood experiences and suicide attempts among those with mental and
substance use disorders.
AB - Using the 2012-2013 National Epidemiologic Survey on Alcohol and Related
Conditions data, we examined the associations of ten types of adverse childhood
experiences (ACEs) with (1) lifetime suicide attempts and (2) number and age of
attempts among U.S. adults aged 18+. In a case-control design, suicide attempters
(5.14% of the full sample) were matched with never attempters (matched sample
N=3912) on nine mental and substance use disorders. ACE rates were higher among
attempters (3.30 [SE=0.07]) than their matched controls (2.19 [SE=0.06]). Results
from multivariable logistic regression analyses showed that sexual abuse and
parental/other family member's mental illness were associated with increased odds
of having attempted suicide among both genders, and emotional neglect was also a
factor for men. Population attributable risk fractions for sexual abuse were
25.75% for women and 8.56% for men. Sexual abuse and a higher number of ACEs were
also related to repeated suicide attempts. A higher number of ACEs was associated
with a younger first attempt age. Gay/bisexual orientation in men and the lack of
college education in both genders were significant covariates. In conclusion,
this study underscores that ACEs are significantly associated with lifetime
suicide attempts even when mental and substance use disorders are controlled.
PMID- 28500925
TI - Revisiting racial disparities in access to surgical management of drug-resistant
temporal lobe epilepsy post implementation of Affordable Care Act.
AB - OBJECTIVES: Prior to enactment of the Affordable Care Act(ACA), several reports
demonstrated remarkable racial disparities in access to surgical care for
epileptic patients. Implementation of ACA provided healthcare access to 7-16
million uninsured Americans. The current study investigates racial disparity post
ACA era in (1) access to surgical management of drug-resistant temporal lobe
epilepsy (DRTLE); (2) short-term outcomes in the surgical cohort. PATIENT AND
METHODS: Adult patients with DRTLE registered in the National Inpatient Sample
(2012-2013) were identified. Association of race (African Americans and other
minorities with respect to Caucasians) with access to surgical management of TLE,
and short-term outcomes [discharge disposition, length of stay (LOS) and hospital
charges] in the surgical cohort were investigated using multivariable regression
techniques. RESULTS: Of the 4062 patients with DRTLE, 3.6%(n=148) underwent
lobectomy. Overall, the mean age of the cohort was 42.35+/-16.33years, and 54%
were female. Regression models adjusted for patient demographics, clinical and
hospital characteristics demonstrated no racial disparities in access to surgical
care for DRTLE. Likewise, no racial disparity was noted in outcomes in the
surgical cohort. CONCLUSION: Our study reflects no racial disparity in access to
surgical care in patients with DRTLE post 2010 amendment of the ACA. The seismic
changes to the US healthcare system may plausibly have accounted for addressing
the gap in racial disparity for epilepsy surgery.
PMID- 28500924
TI - Caregiver parenting and gender attitudes: Associations with violence against
adolescent girls in South Kivu, Democratic Republic of Congo.
AB - Violence against adolescent girls occurs at alarmingly high rates in conflict
affected settings, in part due to their increased vulnerability from their age
and gender. However, humanitarian programming efforts have historically focused
either on child abuse prevention or intimate partner violence prevention and have
not fully addressed the specific needs of adolescent girls, including engagement
of caregivers to reduce risk of violence against adolescent girls. Thus, the
objectives of this analysis are to examine the whether gendered and parental
attitudes of caregivers in South Kivu, Democratic Republic of Congo (DRC) were
associated with their adolescent girls' experiences of violence and girls'
attitudes towards IPV. Cross-sectional data from 869 girls (10-14 years) and
their caregivers (n=764) were drawn from a baseline assessment of a violence
prevention evaluation conducted in 2015. Findings suggest that female caregiver's
gender equitable attitudes for adults may be associated with reduced odds of
sexual abuse and less acceptance of IPV for adolescent girl children. Parenting
attitudes and beliefs and gender equity for girl children were not associated
with violence risk for girls, while increased accepting attitudes of negative
discipline were only associated with lowered odds of sexual abuse. Understanding
of caregivers' attitudes may provide potential insight into how to more
effectively engage and develop programming for caregivers to promote the safety
and well-being of adolescent girls.
PMID- 28500926
TI - Different patterns of gelatinolytic activity in pituitary macro- and
microadenomas.
AB - OBJECTIVE: Gelatinases, Matrix MetalloProteinase(MMP)-2 and MMP-9, belong to zinc
dependent endopeptidases involved in several physiological and pathological
processes including inflammation and tumor development. Because the information
about the involvement of gelatinases in pituitary adenoma (PA) development are
scant, our objective was the analysis of MMP-2 and MMP-9 activity in serum and
tumor tissue of PA patients. PATIENTS AND METHODS: Twenty one patients with PA
(macroadenoma n=18, microadenoma n=3), qualified to the endoscopic resection of
tumors were enrolled. Venous blood samples were collected before the surgery and
PA tissue was collected during the surgery. Tissue material was homogenized in a
buffer containing 0.1M Tris-HCl pH 7.4 and centrifuged. The supernatant was set
to the equal protein content 18MUg/sample. Protein level in tissue samples was
estimated with Bradford method. MMP-2 and MMP-9 analysis in serum and tissue was
performed with gelatin zymography. RESULTS: The proteolytically activated forms
of MMPs were not observed in the analyzed sera. Serum activities of MMP-2 and MMP
9 did not statistically differ between patients with micro and macroadenomas. The
analysis of material obtained from tissue of microadenomas showed slightly lower
activities of both forms of MMP-9 (pro-MMP-9 and MMP-9/lipokalin heterodimer).
Simultaneously the increased activity of pro-MMP-2 in comparison to macroadenomas
was observed. Although differences observed did not reach statistical
significance, only in the case of microadenomas the presence of the active form
of MMP-2 (molecular weight 65kDa band) was observed. CONCLUSION: In the course of
PA growth the change the biochemical profile of the gelatinolytic activity within
the tumor tissue is observed. Initially, the higher activity of MMP-2 in
microadenomas and elevated activity of MMP-9 in macroadenomas were detected.
PMID- 28500927
TI - Comparison of electromagnetic neuronavigation system and free-hand method for
ventricular catheter placement in internal shunt.
AB - OBJECTIVE: Optimal ventricular catheter positioning is able to reduce the risk of
catheter dysfunction, and subsequently the risk of multiple revision surgery. The
objective of our study was to compare the proportion of optimal ventricular
catheter placements in a cohort of patients operated for ventriculoperitoneal
(VP) shunt between a free-hand group and a neuronavigated group. PATIENTS AND
METHODS: Twenty patients with hydrocephalus requiring VP shunt were prospectively
included in this study. Patients were divided into two groups; the ventricular
catheter was positioned using free-hand method (n=10) or magnetic navigation
system (n=10). For the two groups, clinical baseline characteristics, etiology of
hydrocephaly and initial ventricular size were assessed. The main judgment
criterion was the proportion of optimal catheter placements defined by the
presence of all catheter holes in the ventricle, evaluated on post-operative CT
scan. RESULTS: There was no initial difference between the two groups in terms of
hydrocephalus etiology or initial ventricular size. The number of optimal
catheter placements was 6/10 in the neuronavigated group versus 1/10 in the free
hand group (p<0.05). There were no complications during post-operative period in
either cohort. CONCLUSION: In patients suffering from hydrocephaly, the use of an
electromagnetic neuronavigation system for ventricular catheter placement
significantly improved the proportion of optimal catheter placements. Long-term
follow-up is necessary to evaluate the number of revision surgeries and the cost
in each group.
PMID- 28500928
TI - Molecular cloning, characterization and in silico analysis of a thermostable beta
glucosidase enzyme from Putranjiva roxburghii with a significant activity for
cellobiose.
AB - The native Putranjiva roxburghii family 1 glycoside hydrolase enzyme showed beta
D-fucosidase activity in addition to beta-D-glucosidase and beta-D-galactosidase
activities reported in our previous study. A single step concanvalin A affinity
chromatography for native PRGH1 improved the yield and reduced the purification
time. The PRGH1 gene was cloned and overexpressed in E. coli. The full length
gene contained an ORF of 1617 bp encoding a polypeptide of 538 amino acids. The
amino acid sequence of PRGH1 showed maximum similarities to beta-glucosidases and
myrosinases. Both native and recombinant protein showed maximum hydrolytic
activity for pNP-Fuc followed by pNP-Glc and pNP-Gal. Significant enzyme activity
was also observed for cellobiose, however it decreased with increase in chain
length for glycan substrates. The enzyme showed significant resistant to D
glucose concentration up to 500 mM. Mutational studies confirmed the predicted
catalytic acid/base Glu173 and nucleophile Glu389 as key residues for its
activity. Moreover, Glu446 and Asn172 played essential role in substrate binding
by interacting with the -1 subsite of substrates. Bioinformatic analysis
suggested the possible reasons for the broad substrate specificity and other
properties of the enzyme. PRGH1 had high sequence similarity towards S
glucosidase and may be involved in defence. The broad specificity, catalytic
efficiency and thermostability make PRGH1 potentially an important industrial
enzyme.
PMID- 28500929
TI - Oleanane-type glycosides from Pittosporum tenuifolium "variegatum" and P.
tenuifolium "gold star".
AB - The phytochemical study of two cultivars of Pittosporum tenuifolium Banks & Sol.
ex Gaertn, "variegatum" and "gold star", led to the isolation of eight oleanane
type glycosides: seven previously undescribed and a known one. Their aglycons are
oxygenated oleanane derivatives as barringtogenol C, camelliagenin A,
hederagenin, and 22alpha-hydroxyoleanolic acid. Their structures were established
by 2D NMR spectroscopic techniques and mass spectrometry as 3-O-beta-D
galactopyranosyl-(1 -> 2)-[alpha-L-arabinopyranosyl-(1 -> 3)]-beta-D
glucuronopyranosyl-21-O-angeloyl-22-O-acetylbarringtogenol C, 3-O-beta-D
galactopyranosyl-(1 -> 2)-[alpha-L-arabinopyranosyl-(1 -> 3)]-beta-D
glucuronopyranosyl-21,22-di-O-angeloylbarringtogenol C, 3-O-beta-D
galactopyranosyl-(1 -> 2)-[alpha-L-arabinopyranosyl-(1 -> 3)]-beta-D
glucuronopyranosyl-22-O-angeloylcamelliagenin A, 3-O-beta-D-glucopyranosyl-(1 ->
2)-[beta-D-glucopyranosyl-(1 -> 6)]-beta-D-glucopyranosyl-22-O-[(6-O-acetyl)-beta
D-glucopyranosyl]camelliagenin A, 3-O-beta-D-galactopyranosyl-(1 -> 2)-[alpha-L
arabinofuranosyl-(1 -> 4)]-beta-D-glucuronopyranosylhederagenin 28-O-beta-D
glucopyranosyl ester, 3-O-alpha-L-arabinofuranosyl-(1 -> 4)-beta-D
glucuronopyranosylhederagenin 28-O-beta-D-glucopyranosyl ester, 3-O-beta-D
galactopyranosyl-(1 -> 2)-[alpha-L-arabinofuranosyl-(1 -> 4)]-beta-D
glucuronopyranosyl-22alpha-hydroxyoleanolic acid 28-O-beta-D-glucopyranosyl
ester, and the known ilexoside XLIX. These results represent a significative
contribution to the chemotaxonomy of the genus Pittosporum, highlighting
hederagenin-type saponins as chemotaxonomic markers of P. tenuifolium cultivars.
PMID- 28500930
TI - Micro-computed tomography, scanning electron microscopy and energy X-ray
spectroscopy studies of facet joint degeneration: A comparison to clinical
imaging.
AB - Segmental degeneration in the human lumbar spine affects both the intervertebral
discs and facet joints. Facet joint degeneration not only affects the cartilage
surface, but also alters the cellular properties of the cartilage tissue and the
structure of the subchondral bone. The primary focus of this study is the
investigation of these microstructural changes that are caused by facet joint
degeneration. Microstructural analyses of degenerated facet joint samples,
obtained from patients following operative lumbar interbody fusion, have not
previously been extensively investigated. This study analyzes human facet joint
samples from the inferior articular process using scanning electron microscopy,
micro-computed tomography, and energy dispersive X-ray spectroscopy to evaluate
parameters of interest in facet joint degeneration such as elemental composition,
cartilage layer thickness and cell density, calcification zone thickness,
subchondral bone portion, and trabecular bone porosity. These microstructural
analyses demonstrate fragmentation, cracking, and destruction of the cartilage
layer, a thickened calcification zone, localized calcification areas, and cell
cluster formation as pathological manifestations of facet joint degeneration. The
detailed description of these microstructural changes is critical for a
comprehensive understanding of the pathology of facet joint degeneration, as well
as the subsequent development and efficacy analysis of regenerative treatment
strategies.
PMID- 28500931
TI - The influence of polycyclic aromatic hydrocarbons on lung function in a
representative sample of the Canadian population.
AB - We investigated the associations between exposure to polycyclic aromatic
hydrocarbons (PAHs) and selected respiratory physiologic measures in cycles 2 and
3 of the Canadian Health Measures Survey, a nationally representative population
sample. Using generalized linear mixed models, we tested the association between
selected PAH metabolites and 1-second forced expiratory volume (FEV1), forced
vital capacity (FVC), and the ratio between the two (FEV1/FVC) in 3531 people
from 6 to 79 years of age. An interquartile change in urinary PAH metabolite was
associated with significant decrements in FEV1 and FVC for eight PAHs, 2
hydroxynapthalene, 1-, and 2-hydroxyphenanthrene, 2-, 3-, and 9-hydroxyfluorene
and 3- and 4-hydroxyphenanthrene. Exposure to PAH may negatively affect lung
function in the Canadian population.
PMID- 28500933
TI - Functional consequences of inhibitory plasticity: homeostasis, the excitation
inhibition balance and beyond.
AB - Computational neuroscience has a long-standing tradition of investigating the
consequences of excitatory synaptic plasticity. In contrast, the functions of
inhibitory plasticity are still largely nebulous, particularly given the
bewildering diversity of interneurons in the brain. Here, we review recent
computational advances that provide first suggestions for the functional roles of
inhibitory plasticity, such as a maintenance of the excitation-inhibition
balance, a stabilization of recurrent network dynamics and a decorrelation of
sensory responses. The field is still in its infancy, but given the existing body
of theory for excitatory plasticity, it is likely to mature quickly and deliver
important insights into the self-organization of inhibitory circuits in the
brain.
PMID- 28500932
TI - Mass spectral characterization of tabun-labeled lysine biomarkers in albumin.
AB - Tabun has been shown to form phosphylated adducts on tyrosine residues in albumin
in vivo and in vitro. However, in this work, tabun-labeled lysine adducts were
found in albumin. Three types of albumin were treated with overdose of tabun in
vitro and 17 tabun-labeled lysine residues were found: K4, K12, K224, K377, and
K524 in bovine albumin, K186, K188, K212, K329, K414, and K525 in leporine
albumin, and K79, K186, K188, K212, K376, and K525 in rat albumin. To investigate
the modification of tabun in vivo, three leporines were injected with 0.8*LD50
dose of tabun. The results showed that the labeled lysine residues in vivo, were
consistent with modified lysines in vitro. Structure characteristics and the
binding mode of 6 tabun-labeled lysines of leporine albumin were further analyzed
using theory simulation and molecular docking in Discovery Studio. For the first
time, we show that tabun-labeled lysine peptides are found in vivo and in vitro.
These modified lysine peptides are good biomarkers for exposure to tabun in
albumin of leporine and rat.
PMID- 28500934
TI - Interactions of natural resins and pigments in works of art.
AB - The degradation process involving the formation of metal soaps in drying oils is
a well-known problem due to cations from pigments reacting with free fatty acids
from the oil. The aggregation of these carboxylates in semi-crystalline
structures can lead to eruptions through the paint layers and 'blooming' on the
surface. In this work, the metal soaps formation in presence of natural resins
has been assessed and studied by means of Fourier transform infrared spectroscopy
with experiments concerning the ageing of drying oil and different natural resins
(shellac, dammar and colophony) in the presence of common historic pigments
(smalt, ochre, umber, azurite, lead white, zinc white and titanium white).
Mixtures of resins and pigments have been exposed to photo-ageing in solar box up
to 1000h, thermal ageing at 50 degrees C up to 1100h and 6month of room
conditions exposure as reference. The decrease in the intensity of the carbonyl
band in the spectra, as well as the contemporary increase of the metal
carboxylates (in the range from 1500 to 1650cm-1) absorption bands, were used as
the main indicators of metal soap formation. It has been observed that some
pigments, particularly zinc white and smalt, present a 'catalytic' effect
favouring the simultaneous formation of associated oxalates. The formation of
oxalates and different degradation products from natural resins in the presence
of pigments is particularly important, as it deeply affects the removability of
varnishes and, more generally, the cleaning processes. Moreover, it permanently
modifies the interface between painting and varnish layers as well as the
aesthetic aspects of the painted surfaces. The influence of natural resins
reactivity with pigments and their role in the oxalate formation is an issue
still unexplored.
PMID- 28500935
TI - Enhanced pseudocapacitive performance of electroactive p-type conductive polymer
in the presence of 1-octadecyl-3-methylimidazolium bromide.
AB - In present work, for improving the electrochemical performance of conductive
polymer, POAP/1-octadecyl-3-methylimidazolium Bromide ([OMD]Br) composite films
have been fabricated by POAP electropolymerization in the presence of [OMD]Br as
active electrodes for electrochemical supercapacitors. Different electrochemical
methods including galvanostatic charge discharge experiments, cyclic voltammetry
and electrochemical impedance spectroscopy have been applied to study the system
performance. Analyses of DFT results show that the atomic-scale electronic
properties are generally depend on the bonding and electronic molecular
structures (and thus their variation with the external bias in real nano
electrochemical circuits). The supercapacity behavior of the composite film was
attributed to the (i) high active surface area of the composite, (ii) charge
transfer along the polymer chain due to the conjugation form of the polymer and
finally (iii) synergism effect between conductive polymer and [OMD]Br.
PMID- 28500936
TI - Facile hydrothermal synthesis of urchin-like cobalt manganese spinel for high
performance supercapacitor applications.
AB - A facile hydrothermal method has been adopted to synthesize the spherical urchin
like hierarchical CoMn2O4 nanostructures on the nickel foam substrate. The as
synthesized urchins have an average diameter of ~3-7MUm with numerous self
assembled nanoneedles grown radically in all the directions from its center with
a huge void space between them. For comparison, we have also studied the
electrochemical as well as other physicochemical properties of parent simple
Co3O4 and MnO2 materials, which were also synthesized by a similar hydrothermal
method. The results show that CoMn2O4 electrode displayed significantly higher
(more than two times) areal and specific capacitances compared to Co3O4 and MnO2
electrodes with excellent capacitance retention and Coulombic efficiency.
Moreover, the energy and power densities obtained for CoMn2O4 electrode are also
far higher than the parent Co3O4 and MnO2. Long-term cycling tests of CoMn2O4
electrode shows the improved capacitance with high rate capability up to 6000
cycles indicating their potential for high performance supercapacitor
applications. The better electrochemical performance of CoMn2O4 electrode can be
attributed to the smart urchin-like nanostructures, which has several advantages
like, more electroactive sites for faradic reactions emerging from the two metal
ions, higher electronic/ionic conductivity and fast electrolyte transportation
kinetics promoted by unique morphology.
PMID- 28500937
TI - Computational methodology for determining textural properties of simulated porous
carbons.
AB - We have refined and improved the computational efficiency of the TriPOD
technique, used to determine the accessible characteristics of porous solids with
a known configuration of solid atoms. Instead of placing a probe molecule
randomly, as described in the original version of the TriPOD method (Herrera et
al., 2011), we implemented a scheme for dividing the porous solid into 3D-grids
and computing the solid-fluid potential energies at these grid points. We
illustrate the potential of this technique in determining the total pore volume,
the surface area and the pore size distribution of various molecular models of
porous carbons, ranging from simple pore models to a more complex simulated
porous carbon model; the latter is constructed from a canonical Monte Carlo
simulation of carbon microcrystallites of various sizes.
PMID- 28500938
TI - Importance of crystallinity of anchoring block of semi-solid amphiphilic triblock
copolymers in stabilization of silicone nanoemulsions.
AB - Polymer emulsifiers solidified at the interface between oil and water can provide
exceptional dispersion stability to emulsions due to the formation of unique semi
solid interphase. Our recent works showed that the structural stability of
paraffin-in-water emulsions highly depends on the oil wettability of hydrophobic
block of methoxy poly(ethylene glycol)-block-poly(epsilon-caprolactone) (mPEG-b
PCL). Here we investigate the effects of the crystallinity of hydrophobic block
of triblock copolymer-based emulsifiers, PCLL-b-PEG-b-PCLL, on the colloidal
properties of silicone oil-in-water nanoemulsions. The increased ratio of l
lactide to epsilon-caprolactone decreases the crystallinity of the hydrophobic
block, which in turn reduces the droplet size of silicone oil nanoemulsions due
to the increased chain mobility at the interface. All of the prepared
nanoemulsions are very stable for a month at 37 degrees C. However, the exposure
to repeated freeze-thaw cycles quickly destabilizes the nanoemulsions prepared
using the polymer with the reduced crystallinity. This work demonstrates that the
anchoring chain crystallization in the semi-solid interphase is critically
important for the structural robustness of nanoemulsions under harsh physical
stresses.
PMID- 28500939
TI - Novel molecularly imprinted polymer based on beta-cyclodextrin@graphene oxide:
Synthesis and application for selective diphenylamine determination.
AB - A sensitive and selective molecularly imprinted polymer (MIP) for the
determination of diphenylamine (DPA) was developed based on host-guest
interactions of a cyclodextrin-based polymer which possesses an inherent affinity
for the target. The proposed GO@MIP has been prepared using the graphene oxide
(GO) sheets as surface of polymerization, DPA as target molecule, beta
cyclodextrin (beta-CD) and acrylamide (AM) as functional monomers,
azobisisobutyronitrile (AIBN) as initiator and N, N methylene bisacrylamide
(MBAm) as crosslinker which denoted as GO@MIP nanocomposite. The MIP sites were
formed by the inclusion complex through interaction of DPA and beta-CD, followed
by extraction of target. The resulting GO@MIP nanocomposite possess a fast
adsorption kinetics, highly improved imprinting effect, high adsorption capacity,
and it can be applied to fast extraction of DPA. The resultant GO@MIP
nanocomposite was characterized using the Fourier transform infrared spectroscopy
(FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA) scanning
electron microscope (SEM) and energy-dispersive spectroscopy (EDS) analysis. On
the other hand, the non-imprinted polymer (GO@NIP nanocomposite) has been
synthesized and was used in the adsorption experiments. The MIP exhibited good
affinity with a maximum adsorption capacity of 95.98mgg-1 and excellent
selectivity toward DPA than other structural analogues such as 2-amino
benzophenone and dithizone.
PMID- 28500940
TI - Efficient catalytic hydration of cyanamides in aqueous medium and in the presence
of Naringin sulfuric acid or green synthesized silver nanoparticles by using
Gongronema latifolium leaf extract.
AB - In this paper, a novel, efficient and green method for the preparation of
Naringin sulfuric acid (NSA) as a Bronsted acid organocatalyst and silver
nanoparticles (Ag NPs) by using Gongronema latifolium leaf extract as a reducing
and stabilizing agent is introduced. The catalysts were characterized using the
powder XRD, SEM, EDS, TEM, UV-Vis and FT-IR spectroscopy. Afterward, the
catalytic activity of synthesized NSA and Ag NPs were investigated for the
synthesis of N-monosubstituted ureas via the hydration of cyanamides in aqueous
medium. All products were obtained in good to excellent yields. These methods
provided several advantages such as shorter reaction time, simpler work-up and
higher yield.
PMID- 28500941
TI - Direct exfoliation of graphite in water with addition of ammonia solution.
AB - To bring graphene closer to its real-world applications, finding a green, low
cost, environment-friendly and less toxic solvent for production of high-quality
graphene is highly demanded. However, water, the most widely used green solvent,
is generally considered to be a poor solvent for hydrophobic graphene. In this
study, we exfoliate graphene nanosheets directly in basic water without
surfactants, polymers or organic solvents. The addition of a small amount of
ammonia solution achieves the exfoliation of few-layer graphene nanosheets from
pristine graphite. Diverse characterization methods are employed to investigate
the morphology and quality of as-prepared graphene sheets. The release of gaseous
ammonia plays the key role in exfoliation of graphene. The concentration of
stable graphene dispersions can reach 0.058mg/mL.
PMID- 28500942
TI - Synthesis of high surface area mesoporous MnO2 via a "metastable" aqueous
interfacial reaction.
AB - In this work, a metastable aqueous interface was fabricated for synthesizing
mesoporous and high surface area MnO2. When urea was used as the additive,
hierarchical spheres self-organized from ultrathin nano-sheets were obtained. Its
porous structure could be controlled through adjusting the urea concentration,
and a maximum surface area of 407m2 g-1 was achieved by this method, which is
larger than the reported values. Due to the porous structure and high surface
area, as-prepared MnO2 exhibited a specific capacitance of 775.4 F g-1 at a
current density of 0.1 A g-1, and exhibited a 63.5% capacitance retention when
the current density was increased from 0.1 A g-1 to 5A g-1. Durability studies
showed a 63.7% capacitance retention after 2500 cycles. The metastable
interfacial reaction approach could also be extended to other alloys with large
surface area and porous structure, such as CoB alloy. This method provides a
simple and low-cost method to synthesize high surface area and mesoporous
materials.
PMID- 28500943
TI - Quantitative interpretation of PAMAM dendrimers adsorption on silica surface.
AB - Understanding the dendrimer-solid support interaction is of great importance for
dendrimer-based drug delivery system design. The maximum surface coverage on a
hydrophilic silica surface was determined using the quartz crystal microbalance
with dissipation monitoring (QCM-D) and multi-parametric surface plasmon
resonance (MP-SPR) methods: the adsorption process depends on ionic strength and
pH of solutions. The effectiveness of G6 adsorption is mainly determined by the
range of electrostatic inter-dendrimer interactions and dendrimer-silica surface
interactions. Changes in ionic strength have a strong effect on the binding
affinity of dendrimers to the surface. The trends in the binding affinity and the
surface saturation amount correspond well with the degree of change of
protonation of the adsorbed molecules. The development of new research techniques
makes it possible to attain a more profound understanding of the self-assembling
behaviour of dendrimers. The comparison of QCM-D and MP-SPR allowed the
estimation that the dendrimer film contains approximately 70% water. These
results indicate that 6th generation PAMAM dendrimers form very hydrated films on
silica surfaces. In this case the number of water molecules associated per
dendrimer molecule varied from 10,450 to 9,200. The hydration of dendrimer films
seems to be a crucial aspect of their implementation. This data confirmed that
dendrimers are very promising candidates for many biological applications.
PMID- 28500944
TI - The structure evolution of colloidal aggregates composed of monodisperse silica
nanospheres.
AB - In this work, colloidal aggregates, such as higher-order clusters with polyhedral
geometry, supraparticles with intermediate packing ordering, different inner
structured supraballs with face-centered cubic ordering were produced through
self-assembly of different quantities of monodisperse silica nanospheres in water
in-oil emulsion droplets which were formed by ultrasonic dispersion of silica
nanospheres suspension into different solvents. The structure evolution of
colloidal aggregates as a function of the number of constituent silica
nanospheres was studied in this article. It was found that the inner structures
of colloidal aggregates would be changed with increasing of the number of
constituent silica nanospheres in different solvents. In the case of n-octanol
being as solvent, the supraparticles were the transition structure for higher
order clusters into supraballs with hollow structure, while in silicone oil, the
supraparticles were the transition structure for higher-order clusters into solid
structured supraballs.
PMID- 28500945
TI - Carbohydrate-based electrochemical biosensor for detection of a cancer biomarker
in human plasma.
AB - Autocrine motility factor (AMF) is a tumor-secreted cytokine that stimulates
tumor cell motility in vitro and metastasis in vivo. AMF could be detected in
serum or urine of cancer patients with worse prognosis. Reported as a cancer
biomarker, AMF secretion into body fluids might be closely related to metastases
formation. In this study, a sensitive and specific carbohydrate-based
electrochemical biosensor was designed for the detection and quantification of a
protein model of AMF, namely phosphoglucose isomerase from rabbit muscle (RmPGI).
Indeed, RmPGI displays high homology with AMF and has been shown to have AMF
activity. The biosensor was constructed by covalent binding of the enzyme
substrate d-fructose 6-phosphate (F6P). Immobilization was achieved on a gold
surface electrode following a bottom-up approach through an aminated surface
obtained by electrochemical patterning of ethylene diamine and terminal amine
polyethylene glycol chain to prevent non-specific interactions. Carbohydrate
protein interactions were quantified in a range of 10 fM to 100nM. Complex
formation was analyzed through monitoring of the redox couple Fe2+/Fe3+ by
electrochemical impedance spectroscopy and square wave voltammetry. The F6P
biosensor demonstrates a detection limit of 6.6 fM and high selectivity when
compared to other non-specific glycolytic proteins such as d-glucose-6-phosphate
dehydrogenase. Detection of protein in spiked plasma was demonstrated and
accuracy of 95% is obtained compared to result obtained in PBS (phosphate
buffered saline). F6P-biosensor is a very promising proof of concept required for
the design of a carbohydrate-based electrochemical biosensor using the enzyme
substrate as bioreceptor. Such biosensor could be generalized to detect other
protein biomarkers of interest.
PMID- 28500946
TI - PA-Tb-Cu MOF as luminescent nanoenzyme for catalytic assay of hydrogen peroxide.
AB - Metal organic frameworks (MOFs) with flexible structures and components have
aroused great interest in designing functional materials. In this work, we
designed and made a kind of PA-Tb-Cu MOF nanoenzyme capable of emitting
fluorescence for the catalytic reaction of hydrogen peroxide (H2O2). Luminescent
Tb3+, catalytic Cu2+ and bridging ligand were assembled and integrated into a
single material nanoenzyme. This PA-Tb-Cu MOF nanoenzyme not only possessed
excellent catalytic activity comparable to horseradish peroxidase but also can
real-time fluorescently indicate the concentration of H2O2 as low as 0.2uM during
catalysis. Luminescent PA-Tb-Cu MOF nanoenzyme did not need a common combined use
of natural/artificial enzymes and chromogenic reactions for the quantification of
H2O2 in widely-used enzyme-catalytic reactions. The present strategy assembled
directly from functional ions/molecules provides a new way for the design and
development of smart, multifunctional artificial enzymes for wide applications in
biocatalysis, bioassays and nano-biomedicine.
PMID- 28500947
TI - Electrochemical latent redox ratiometric probes for real-time tracking and
quantification of endogenous hydrogen sulfide production in living cells.
AB - Hydrogen sulfide (H2S) was discovered as a third gasotransmitter in biological
systems and recent years have seen a growing interest to understand its
physiological and pathological functions. However, one major limiting factor is
the lack of robust sensors to quantitatively track its production in real-time.
We described a facile electrochemical assay based on latent redox probe approach
for highly specific and sensitive quantification in living cells. Two chemical
probes, Azido Benzyl ferrocene carbamate (ABFC) and N-alkyl Azido Benzyl
ferrocene carbamate (NABFC) composed of azide trigger group were designed. H2S
molecules specifically triggered the release of reporters from probes and the
current response was monitored using graphene oxide film modified electrode as
transducer. The detection limits are 0.32uM (ABFC) and 0.076uM (NABFC) which are
comparable to those of current sensitive methods. The probes are successful in
the determination of H2S spiked in whole human blood, fetal bovine serum, and E.
coli. The continuous monitoring and quantification of endogenous H2S production
in E. coli were successfully accomplished. This work lays first step stone
towards real-time electrochemical quantification of endogenous H2S in living
cells, thus hold great promise in the analytical aspects of H2S.
PMID- 28500948
TI - Using reduced graphene oxide-Ca:CdSe nanocomposite to enhance
photoelectrochemical activity of gold nanoparticles functionalized tungsten oxide
for highly sensitive prostate specific antigen detection.
AB - An ultrasensitive sandwich-type photoelectrochemical (PEC) immunosensor was
constructed for the detection of prostate specific antigen (PSA). In this work,
Au-nanoparticle-loaded tungsten oxide (WO3-Au) hybrid composites was applied as
PEC sensing platform, while Ca ions doped CdSe equipped on the conducting
framework of reduced graphene oxide (rGO-Ca:CdSe) nanocomposites were employed as
the signal amplification probe. As for WO3-Au, massive Au nanoparticles were
formed on the surface of WO3 without any additional reducing agent, providing a
novel nanocarriers for anchoring plenty of the primary antibodies due to the
large specific surface area and good biocompatibility by chemical bonding between
Au nanoparticles and -NH2 of antibodies. Besides, the incorporation of the rGO
and the doping of Ca ions could improve the conductivity and hinder the
recombination of electron-hole pairs of CdSe nanoparticles effectively, thereby
enhancing the photocurrent conversion efficiency. Based on the sandwich
immunoreaction, the primary antibody was immobilized onto WO3-Au substrate, after
the formed rGO-Ca:CdSe labels were captured onto the electrode surface via the
specific antibody-antigen interaction, the photocurrent intensity could be
further enhanced due to the sensitization effect. Under the optimal conditions,
the proposed PEC immunosensor shows a linear relationship between photocurrent
variation and the logarithm of PSA concentration in the wide range of 5pgmL-1 to
50ngmL-1 with a low detection limit of 2.6pgmL-1 (S/N=3). Moreover, it also
presented good stability and acceptable specificity, indicating the potential
applications in clinical diagnostics.
PMID- 28500949
TI - Human health risks for Legionella and Mycobacterium avium complex (MAC) from
potable and non-potable uses of roof-harvested rainwater.
AB - A quantitative microbial risk assessment (QMRA) of opportunistic pathogens
Legionella pneumophila (LP) and Mycobacterium avium complex (MAC) was undertaken
for various uses of roof-harvested rainwater (RHRW) reported in Queensland,
Australia to identify appropriate usages and guide risk management practices.
Risks from inhalation of aerosols due to showering, swimming in pools topped up
with RHRW, use of a garden hose, car washing, and toilet flushing with RHRW were
considered for LP while both ingestion (drinking, produce consumption, and
accidental ingestion from various activities) and inhalation risks were
considered for MAC. The drinking water route of exposure presented the greatest
risks due to cervical lymphadenitis and disseminated infection health endpoints
for children and immune-compromised populations, respectively. It is therefore
not recommended that these populations consume untreated rainwater. LP risks were
up to 6 orders of magnitude higher than MAC risks for the inhalation route of
exposure for all scenarios. Both inhalation and ingestion QMRA simulations
support that while drinking, showering, and garden hosing with RHRW may present
the highest risks, car washing and clothes washing could constitute appropriate
uses of RHRW for all populations, and toilet flushing and consumption of lettuce
irrigation with RHRW would be appropriate for non- immune-compromised
populations.
PMID- 28500950
TI - Determining the effect of cartridge case coatings on GSR using post-fire priming
cup residue.
AB - Ammunition is typically composed of a lead-based priming mixture which
contributes to the characteristics most commonly used for the identification of
gunshot residue (GSR). Due to the health risks often associated with lead, the
use of lead-free primers in ammunitions is becoming more popular. Thus, the
presence of GSR is becoming more difficult to discern based on the traditional
means, i.e. the presence of lead (Pb), barium (Ba), and antimony (Sb). While
research has been conducted on the differences between lead-based and lead-free
muzzle discharge residue, few have researched other components of ammunition
which may lead to other means of characterizing GSR. This research, therefore,
covers that gap by focusing on the priming cup present in ammunition and the
residue which may originate from it, that can contribute to muzzle discharge
residue. In this study, a lead-based and a lead-free ammunition from four
different manufacturers were chosen. The cartridges were fired using a Glock 17,
9mm Parabellum, collected post-fire, and subsequently de-primed resulting in the
removal of the anvil. The GSR present on the anvils and cups was analyzed using
scanning electron microscopy coupled with energy dispersive x-ray spectrometry
(SEM-EDX). The data was then processed using unit vector analysis for
normalization and analyzed using principal component analysis (PCA) and linear
discriminant analysis (LDA). This data was then used to determine the components
of the cartridge case which contribute to GSR and develop a method of
characterization between lead-free and lead-based ammunition. Such a method will
improve the detection of GSR by strengthening the criteria of identification.
PMID- 28500951
TI - Hydrogen peroxide induces cell proliferation and apoptosis in pulp of rats after
dental bleaching in vivo: Effects of the dental bleaching in pulp.
AB - OBJECTIVE: This study provides an in vivo evaluation of the inflammatory
response, levels of cell proliferation and apoptosis, and the presence of
necrosis after dental bleaching with two concentrations of hydrogen peroxide
(H2O2). DESIGN: Wistar rats were divided into Control (placebo gel), BLUE (20%
H2O2, 1*50min), and MAXX (35% H2O2, 3*15min) groups. At 2 and 30days, the rats
were killed (n=10). The jaws were processed for histology analysis and PCNA and
Caspase-3-cleaved immunohistochemistry, and data were submitted to the Mann
Whitney or ANOVA test (P<0.05). RESULTS: At 2days, the MAXX group showed necrosis
and the BLUE group revealed moderate inflammation on the occlusal third of the
crown (P<0.05). At 30days, tertiary dentin had formed and there was an absence of
inflammation. The level of cell proliferation was higher in the middle third of
the BLUE group (P<0.05), and cervical of MAXX at 2days (P<0.05), decreasing at
30days. The apoptosis was present at 2days, particularly in the cervical third of
the crown in the bleached groups (P<0.05), with a decrease only at 30days in the
BLUE group (P<0.05). CONCLUSIONS: The concentration of H2O2 influences effects on
the pulp tissue, where a higher concentration of H2O2 can cause necrosis in the
pulp and a prolonged effect within the apoptotic process; lower concentrations of
H2O2 provide moderate inflammation, cell proliferation and apoptosis with a
reduction of these processes over time.
PMID- 28500953
TI - Induced not just right and incompleteness experiences in OCD patients and non
clinical individuals: An in vivo study.
AB - BACKGROUND AND OBJECTIVES: Research on incompleteness and not-just right
experiences, (INC/NJREs) indicate that some OCD symptom dimensions are motivated
by these experiences rather than by anxiety. Most published data are
correlational, using non-clinical individuals. This study sought to examine
INC/NJREs in vivo in non-clinical and OCD individuals. METHODS: Study 1: Ninety
three undergraduates were randomly assigned to a INC/NJREs induction (n=44) or
non-induction task (n=47). Scores on self-reports assessing INC, NJREs, OCD,
Anxiety, and Depression were also recorded. Study 2: Twenty adults with OCD
performed the induction task and completed the same questionnaire-packet as the
non-clinical participants. RESULTS: Study 1: The induction-group scored higher on
several DVs of the experimental task, as INC/NJREs and uncomfortable physical
sensations predicted impulses/urges to do something. All the DVs correlated with
INC, NJREs, and OCD symptoms. Anxiety was only related to suppressing
difficulties of the most intense sensation. Study 2: Results were comparable to
those found in non-clinical people. Induced INC/NJREs correlated with compulsions
severity and were associated with ordering, washing, and hoarding symptoms. OCDs
did not differ from non-clinical subjects in the number of induced INC/NJREs, but
they were more disturbing, difficult to suppress, and instigated more urges to do
in OCDs. LIMITATIONS: The small group of OCDs and the lack of a non-OCD clinical
group kept us from drawing conclusions about the specificity of INC/NJREs to some
OCD symptoms. CONCLUSIONS: Findings support the role of INC/NJREs as stimuli
triggering urges and/impulses to do and their impact on OCD severity.
PMID- 28500952
TI - Isolation and characterization of lymphoid enhancer factor-1-positive deciduous
dental pulp stem-like cells after transfection with a piggyBac vector containing
LEF1 promoter-driven selection markers.
AB - OBJECTIVE: Lymphoid enhancer-binding factor-1 (LEF1) is a 48-kD nuclear protein
that is expressed in pre-B and T cells. LEF1 is also an important member of the
Wnt/beta-catenin signaling pathway that plays important roles in the self-renewal
and differentiation of embryonic stem cells. We speculated that LEF1 might
function in the stem cells from human exfoliated deciduous teeth (SHED). In this
study, we attempted to isolate such LEF1-positive cells from human deciduous
dental pulp cells (HDDPCs) by genetic engineering technology, using the human
LEF1 promoter. DESIGN: A piggyBac transposon plasmid (pTA-LEN) was introduced
into HDDPCs, using the Neon(r) transfection system. After G418 selection, the
emerging colonies were assessed for EGFP-derived fluorescence by fluorescence
microscopy. Reverse transcription polymerase chain reaction (RT-PCR) analysis was
performed using RNA isolated from these colonies to examine stem cell-specific
transcript expression. Osteoblastic or neuronal differentiation was induced by
cultivating the LEF1-positive cells with differentiation-inducing medium.
RESULTS: RT-PCR analysis confirmed the expression of several stem cell markers,
including OCT3/4, SOX2, REX1, and NANOG, in LEF1-positive HDDPCs, which could be
differentiated into osteoblasts and neuronal cells. CONCLUSIONS: The isolated
LEF1-positive HDDPCs exhibited the properties of stem cells, suggesting that LEF1
might serve as a marker for SHED.
PMID- 28500954
TI - Finger forces in fastball baseball pitching.
AB - Forces imparted by the fingers onto a baseball are the final, critical aspects
for pitching, however these forces have not been quantified previously as no
biomechanical technology was available. In this study, an instrumented baseball
was developed for direct measurement of ball reaction force by individual fingers
and used to provide fundamental information on the forces during a fastball
pitch. A tri-axial force transducer with a cable having an easily-detachable
connector were installed in an official baseball. Data were collected from 11
pitchers who placed the fingertip of their index, middle, ring, or thumb on the
transducer, and threw four-seam fastballs to a target cage from a flat mound. For
the index and middle fingers, resultant ball reaction force exhibited a bimodal
pattern with initial and second peaks at 38-39ms and 6-7ms before ball release,
and their amplitudes were around 97N each. The ring finger and thumb produced
single-peak forces of approximately 50 and 83N, respectively. Shear forces for
the index and middle fingers formed distinct peak at 4-5ms before release, and
the peaks summed to 102N; a kinetic source for backspin on the ball. An
additional experiment with submaximal pitching effort showed a linear
relationship of peak forces with ball velocity. The peak ball reaction force for
fastballs exceeded 80% of maximum finger strength measured, suggesting that
strengthening of the distal muscles is important both for enhancing performance
and for avoiding injuries.
PMID- 28500955
TI - Economic evaluation of nurse practitioner and clinical nurse specialist roles: A
methodological review.
AB - BACKGROUND: Advanced practice nurses (e.g., nurse practitioners and clinical
nurse specialists) have been introduced internationally to increase access to
high quality care and to tackle increasing health care expenditures. While
randomised controlled trials and systematic reviews have demonstrated the
effectiveness of nurse practitioner and clinical nurse specialist roles, their
cost-effectiveness has been challenged. The poor quality of economic evaluations
of these roles to date raises the question of whether current economic evaluation
guidelines are adequate when examining their cost-effectiveness. OBJECTIVE: To
examine whether current guidelines for economic evaluation are appropriate for
economic evaluations of nurse practitioner and clinical nurse specialist roles.
METHODS: Our methodological review was informed by a qualitative synthesis of
four sources of information: 1) narrative review of literature reviews and
discussion papers on economic evaluation of advanced practice nursing roles; 2)
quality assessment of economic evaluations of nurse practitioner and clinical
nurse specialist roles alongside randomised controlled trials; 3) review of
guidelines for economic evaluation; and, 4) input from an expert panel. RESULTS:
The narrative literature review revealed several challenges in economic
evaluations of advanced practice nursing roles (e.g., complexity of the roles,
variability in models and practice settings where the roles are implemented, and
impact on outcomes that are difficult to measure). The quality assessment of
economic evaluations of nurse practitioner and clinical nurse specialist roles
alongside randomised controlled trials identified methodological limitations of
these studies. When we applied the Guidelines for the Economic Evaluation of
Health Technologies: Canada to the identified challenges and limitations,
discussed those with experts and qualitatively synthesized all findings, we
concluded that standard guidelines for economic evaluation are appropriate for
economic evaluations of nurse practitioner and clinical nurse specialist roles
and should be routinely followed. However, seven out of 15 current guideline
sections (describing a decision problem, choosing type of economic evaluation,
selecting comparators, determining the study perspective, estimating
effectiveness, measuring and valuing health, and assessing resource use and
costs) may require additional role-specific considerations to capture costs and
effects of these roles. CONCLUSION: Current guidelines for economic evaluation
should form the foundation for economic evaluations of nurse practitioner and
clinical nurse specialist roles. The proposed role-specific considerations, which
clarify application of standard guidelines sections to economic evaluation of
nurse practitioner and clinical nurse specialist roles, may strengthen the
quality and comprehensiveness of future economic evaluations of these roles.
PMID- 28500957
TI - Design & synthesis of novel oxazolone & triazinone derivatives and their
biological evaluation as COX-2 inhibitors.
AB - A new series of oxazolones and triazinones were designed and synthesized and
evaluated against both COX-1 and COX-2 enzymes. Full structure elucidation of the
new derivatives was performed using microanalyses, IR, 1H NMR, 13C NMR and mass
spectra. Most of the derivatives showed good inhibitory activity against COX-2
enzyme specifically compounds IIIc, IIIe, IVd and IVg with IC50 values 0.024,
0.019, 0.011 and 0.014uM compared to celecoxib as reference drug with IC50 value
of 0.05uM. Altogether, these results indicate that these derivatives can be
effective anti-inflammatory agents.
PMID- 28500956
TI - Efficient synthesis of novel dialkyl-3-cyanopropylphosphate derivatives and
evaluation of their anticholinesterase activity.
AB - Based on the broad spectrum of biological activities associated with
organophosphates, a novel type of this class of compounds was synthesized,
bearing a nitrile group, from the sodium alkoxide-catalyzed reaction of
dialkylphosphites with gamma-ketonitriles at 80 degrees C under solvent-free
conditions. A reaction mechanism involving a phospha-Brook type rearrangement is
proposed. Eight title compounds were investigated for their in vitro inhibitory
potency and selectivity against acetylcholinesterase (AChE) and
butyrylcholinesterase (BChE) using Ellman's spectrophotometric method. The
synthesized derivatives exhibited mostly a moderate activity against both
cholinesterases. The IC50 values for BChE were in a smaller concentration range
(5.96-23.35uM) compared to those for AChE inhibition (9.61-53.74uM). The diethyl
3-cyano-1-p-tolylpropylphosphate which displayed the higher dual inhibitory
potency towards both cholinesterases could be considered as a potential candidate
for developing new drugs to treat Alzheimer's disease.
PMID- 28500958
TI - Development of an updated normative data table for hand grip and pinch strength:
A pilot study.
AB - STUDY DESIGN: Pilot cross-sectional clinical measurement. INTRODUCTION: Normative
tables for assessment of grip and pinch strength were developed 30 years ago and
are likely outdated. PURPOSE OF STUDY: To assess suitability of current normative
tables to evaluate hand and grip strength in clinical practice. METHODS: Hand
grip strength (HGS) data were measured in 120 healthy subjects for comparison to
normative values by gender, age, and handedness. RESULTS: Statistically
significant differences in HGS measurements (grip, key pinch, and palmar pinch)
between our measurements and normative data were detected in males and females
regardless of handedness. When the population was stratified by five year age
groups per Mathiowetz Rating Scale and compared to Mathiowetz normal values, 23
out of 120 possible comparisons (19%) had associated p-values <0.10, suggesting
moderate evidence of differences between study and reference values. In simulated
10-year age groups, 23 out of 60 possible comparisons (38%) had relatively large
differences between our measurements and Mathiowetz [20/23 (87%) were greater
than 10% and 8 (35%) were greater that 15%]. Negative differences (N=19) were
more frequent than positive differences (N=4), which indicates our patient
population as a whole has decreased HGS compared to previous populations though
we note this difference in HGS measurements is less in patients over 45 years of
age. CONCLUSIONS: Normative hand strength values need to be further assessed in a
larger study to update normative standards for use in clinical practice. LEVEL OF
EVIDENCE: 2c.
PMID- 28500959
TI - Biomechanical evaluation of implant-supported prosthesis with various tilting
implant angles and bone types in atrophic maxilla: A finite element study.
AB - BACKGROUND AND OBJECTIVE: The purpose of this study is to evaluate and compare
bone stress that occurs as a result of using vertical implants with simultaneous
sinus augmentation with bone stress generated from oblique implants without sinus
augmentation in atrophic maxilla. METHODS: Six, three-dimensional (3D) finite
element (FE) models of atrophic maxilla were generated with SolidWorks software.
The maxilla models were varied for two different bone types. Models 2a, 2b and 2c
represent maxilla models with D2 bone type. Models 3a, 3b and 3c represent
maxilla models with D3 bone type. Five implants were embedded in each model with
different configurations for vertical implant insertion with sinus augmentation:
Model 2a/Model 3a, 30 degrees tilted insertion; Model 2b/Model 3b and 45 degrees
tilted insertion; Model 2c/Model 3c. A 150 N load was applied obliquely on the
hybrid prosthesis. The maximum von Mises stress values were comparatively
evaluated using color scales. RESULTS: The von Mises stress values predicted by
the FE models were higher for all D3 bone models in both cortical and cancellous
bone. For the vertical implant models, lower stress values were found in cortical
bone. Tilting of the distal implants by 30 degrees increased the stress in the
cortical layer compared to vertical implant models. Tilting of the distal implant
by 45 degrees decreased the stress in the cortical bone compared to the 30
degrees models, but higher stress values were detected in the 45 degrees models
compared to the vertical implant models. CONCLUSIONS: Augmentation should be the
first treatment option in atrophic maxilla in terms of biomechanics. Tilted
posterior implants can create higher stress values than vertical posterior
implants. During tilting implant planning, the use of a 45 degrees tilted
implant results in better biomechanical performance in peri-implant bone than 30
degrees tilted implant due to the decrease in cantilever length.
PMID- 28500960
TI - Infrared reflectometry of skin: Analysis of backscattered light from different
skin layers.
AB - We have recently reported infrared spectroscopy of human skin in vivo using
quantum cascade laser excitation and photoacoustic or photothermal detection for
non-invasive glucose measurement . Here, we analyze the IR light diffusely
reflected from skin layers for spectral contributions of glucose. Excitation of
human skin by an external cavity tunable quantum cascade laser in the spectral
region from 1000 to 1245cm-1, where glucose exhibits a fingerprint absorption,
yields reflectance spectra with some contributions from glucose molecules. A
simple three-layer model of skin was used to calculate the scattering intensities
from the surface and from shallow and deeper layers using the Boltzmann radiation
transfer equation. Backscattering of light at wavelengths around 10MUm from the
living skin occurs mostly from the Stratum corneum top layers and the shallow
layers of the living epidermis. The analysis of the polarization of the
backscattered light confirms this calculation. Polarization is essentially
unchanged; only a very small fraction (<3%) is depolarized at 90 degrees with
respect to the laser polarization set at 0 degrees . Based on these findings, we
propose that the predominant part of the backscattered light is due to specular
reflectance and to scattering from layers close to the surface. Diffusely
reflected light from deeper layers undergoing one or more scattering processes
would appear with significantly altered polarization. We thus conclude that a non
invasive glucose measurement based on backscattering of IR light from skin would
have the drawback that only shallow layers containing some glucose at
concentrations only weakly related to blood glucose are monitored.
PMID- 28500961
TI - Influence of polyethylene glycol on the phase transition of poly(butylene
adipate) thin films: Polymorphic control.
AB - Control of the polymorphic crystals formation of poly(butylene adipate) (PBA) is
crucial to tailor its performance. In the present study, we investigated the
effect of polyethylene glycol (PEG) with molecular weight of 400 on the
polymorphic crystal of PBA thin films using x-ray diffraction (XRD), temperature
dependent infrared-reflection absorbance spectroscopy (IRRAS) and two-dimensional
correlation analysis (2DCOS). XRD and IRRAS results suggest that the PBA thin
film tends to grow alpha-form crystal with addition of PEG at room temperature.
Increasing the PEG contribution to 30wt%, the PBA thin film shows alpha-form
crystal only. Temperature-dependent IRRAS spectra indicate that pure PBA thin
film exhibited alpha/beta mixed crystal and the beta-to-alpha transition was
observed during the heating process. After the incorporation of PEG, PEG not only
inhibits the growth of beta crystal but also suppresses the beta-to-alpha
transition during the heating process. In addition, we unexpectedly captured
three different amorphous bands of CO stretching of pure PBA from the
asynchronous 2D correlation spectrum. The band at 1740cm-1 corresponded to the
amorphous phase of PBA at room temperature, whereas 1746 and 1760cm-1
respectively arose from the amorphous phase of PBA melting from alpha-form
crystal and beta-form crystal. This study demonstrated that the crystal form of
PBA can be modified by blending with PEG, providing a new method to control the
crystal modification and physical properties of polymorphic PBA in their blend
system.
PMID- 28500962
TI - The methylation levels of the H19 differentially methylated region in human
umbilical cords reflect newborn parameters and changes by maternal environmental
factors during early pregnancy.
AB - H19 is a tumor-suppressor gene, and changes in the methylation of the H19
differential methylation region (H19-DMR) are related to human health. However,
little is known about the factors that regulate the methylation levels of H19
DMR. Several recent studies have shown that maternal environmental factors during
pregnancy, such as smoking, drinking, chemical exposure, and nutrient intake, can
alter the methylation levels of several genes in fetal tissues. In this study, we
examined the effects of maternal factors on changes in the methylation levels of
H19-DMR in the human umbilical cord (UC), an extra-embryonic tissue. Participants
from the Chiba study of Mother and Children's Health (C-MACH) were enrolled in
this study. Genomic DNA was extracted from UC samples, and the methylation level
of H19-DMR was evaluated by methylation-sensitive high resolution melting
analysis. Individual maternal and paternal factors and clinical information for
newborns at birth were examined using questionnaires prepared in the C-MACH
study, a brief-type self-administered diet history questionnaire (BDHQ) during
early pregnancy (gestational age of 12 weeks), and medical records. Univariate
and multivariate logistic regression analyses indicated that reduced H19-DMR
methylation (<50% methylation) in UC tissues was positively related to decreased
head circumference in newborns [odds ratio (OR) =2.82; 95% confidence intervals
(CI): 1.21-6.87; p=0.0183 and OR =2.51; 95% CI: 1.02-6.46; p=0.0499,
respectively]. Moreover, multiple comparison test showed that H19-DMR methylation
in UC tissues was significantly reduced in the low calorie group (intake of less
than 1,000kcal/day; methylation level: 40.98%; 95% CI: 33.86-48.11) compared with
that in the middle (1,000-1,999kcal/day; methylation level: 51.28%; 95% CI: 48.28
54.27) and high (>=2,000kcal/day; methylation level: 52.16%; 95% CI: 44.81-59.51)
calorie groups (p=0.0054 and 0.047, respectively). In the subpopulations with low
to moderate calorie intake (<2,000kcal/day), reduced H19-DMR methylation in UC
tissues was significantly related to serum homocysteine concentration (OR =0.520;
95% CI: 0.285-0.875; p=0.019), maternal age (OR =1.22; 95% CI: 1.01-1.52;
p=0.049), and serum folate levels (OR =0.917; 95% CI: 0.838-0.990; p=0.040).
These data indicated that H19-DMR methylation levels in human UC tissues could be
modulated by maternal factors during early pregnancy and may affect fetal and
newborn growth.
PMID- 28500963
TI - Sensory profiling of low sodium frankfurter containing garlic products: Adequacy
of Polarized Projective Mapping compared with trained panel.
PMID- 28500964
TI - Dietary linseed oil supplemented with organic selenium improved the fatty acid
nutritional profile, muscular selenium deposition, water retention, and
tenderness of fresh pork.
AB - Cross-bred pigs were fed a control diet (with 0.3ppm sodium selenite and 1.5%
soybean oil) or organic selenium diets (0.3ppm Se-Yeast with 1.5% soybean or
linseed oil) to investigate nutrient supplement effects on meat quality and
oxidative stability. The organic selenium diets increased muscular selenium
content up to 54%, and linseed oil increased n-3 fatty acids two-fold while
lowering the n-6/n-3 fatty acid ratio from 13.9 to 5.9 over the selenite control
diet (P<0.05). Organic selenium yeast treatments with linseed oil reduced pork
drip loss by 58-74% when compared with diets with soybean oil. Lightness of fresh
pork was slightly less for organic selenium groups than inorganic (P<0.05), but
redness was mostly similar. Lipid oxidation (TBARS) and protein oxidation
(sulfhydryl) during meat storage (4 degrees C up to 6days) showed no appreciable
difference (P>0.05) between diets, in agreement with the lack of notable
difference in endogenous antioxidant enzyme activity between these meat groups.
PMID- 28500967
TI - A systematic review on potential mechanisms of minocycline in kidney diseases.
AB - Kidney diseases need specialized health care and still are a reason of death.
There is a large body of evidence that indicates minocycline possesses some
cytoprotective effects beside of antibacterial properties. In this review, we
aimed to explain cytoprotective mechanisms and kidney protection of minocycline.
In order to find the effects of minocycline on kidney diseases a systematic
literature search was performed, according to the guidelines proposed at the
PRISMA statement in the electronic databases, including: PubMed, Scopus, and Web
of Science up to August 2016, using the term 'minocycline' combined either by
'kidney' or 'renal' and published in English language. The following criteria
were included: (1) studies that used minocycline in renal diseases; (2) full-text
articles; (3) English language; (4) no limitation in publications with in-vivo or
in-vitro and human or animal subjects. Our search provided a total of 1056
articles which 1045 of them were discarded due to not meeting the inclusion
criteria. It has been clear that several factors, including apoptosis, oxidative
stress, mitochondrial dysfunction and inflammation have pivotal roles in the
development and progression of kidney diseases. Minocycline protective properties
are via several ways, including anti-apoptotic, free radical scavenging, anti
inflammatory, effect on mitochondrial functions and inhibition of matrix
metalloproteinase. This systematic review confirmed that minocycline could have
significant effects on treatment of renal malfunctions. However, regarding any
possible adverse effects of antibiotics, it appears that more investigation is
still needed in this context.
PMID- 28500966
TI - Synthesis of novel benzylidene analogues of betulinic acid as potent cytotoxic
agents.
AB - Different benzylidene derivatives (15a-o and 16a-o) of betulinic acid were
designed and synthesized in an effort to develop potent anticancer agents. All
the synthesized derivatives along with betulinic acid were evaluated for
cytotoxicity against a panel of five different human cancer cell lines A-549
(Lung), PC-3 (Prostate), HCT 116 (Colon), MCF-7 (Breast) and MIA PaCa-2
(Pancreatic) using SRB assay. Pharmacological results showed that compounds 15b,
15c, 15i, 15k, 16a-c and 16l were found to have promising cytotoxic profile
against various cancer cell lines tested (IC50 1-2 MUM). Best results were
observed for compound 16c with IC50 values 1.5, 1.6, 1.36, 3.5 and 3.2 MUM
against A-549, PC-3, HCT 116, MCF-7 and MIA PaCa-2 cell lines, respectively.
Mechanistic study of compound 16c revealed that it inhibits the colony formation
and restrict the migration in HCT 116 cells in vitro. It also induces growth
arrest with characterized morphological changes and loss of mitochondrial
membrane potential (MMP) in a concentration dependent manner.
PMID- 28500965
TI - Resting state functional connectivity in primary insomnia, generalized anxiety
disorder and controls.
AB - Sleep abnormalities are extremely common in anxiety disorders and may contribute
to their development and persistence. Their shared pathophysiological mechanisms
could thus serve as biomarkers or targets for novel therapeutics. Individuals
with Primary Insomnia were age- and sex-matched to controls and to persons with
Generalized Anxiety Disorder. All underwent fMRI resting-state scans at 3-T. In
Primary Insomnia and controls, sleep was recorded for 2 weeks using diaries and
actigraphy. All participants completed state-anxiety and neuroticism inventories.
Whole-brain connectivity of 6 fear- and extinction-related seeds were compared
between the 3 groups using ANOVA. The only significant between-group main effect
was seen for connectivity between the left amygdala seed and a bilateral cluster
in the rostral anterior cingulate cortex. The latter is believed to exert top
down control over amygdala activity and their interaction may thus constitute an
emotion regulatory circuit. This connectivity was significantly greatest in
controls while Primary Insomnia was intermediate between that of controls and
Generalized Anxiety Disorder. Across Primary Insomnia and control subjects, mean
connectivity decreased with poorer sleep. Across all 3 groups, connectivity
decreased with greater neuroticism and pre-scan anxiety. Decreased top-down
control of the amygdala may increase risk of developing an anxiety disorder with
preexisting Primary Insomnia.
PMID- 28500968
TI - Stability and removal of selected avobenzone's chlorination products.
AB - Stability studies of two avobenzone transformation products: chloro-avobenzone [2
chloro-1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)-1,3-propanedione] and dichloro
avobenzone [2,2-dichloro-1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)-1,3
propanedione] have been performed at different pHs values as well as under UV A
light and compared with the stability of avobenzone, one of the mostly used UV A
filter present in sunscreens. We have additionally investigated the possibility
of application of TiO2 photocatalysis as a method for the removal of them.
Results have shown the differences in pH stability of all three studied compounds
with much slower degradation rate under neutral conditions in comparison to the
acidic ones for all three studied compounds. In the case of photolytic
experiment, performed under UV A light, dichloro-avobenzone exhibited the lowest
UVA stability (half-life 22.4 +/- 0.7 min), while avobenzone and chloro
avobenzone are much more stable and have shown quite similar degradation pattern
(half-lives 126 +/- 16 min and 128 +/- 25 min). Under the photocatalytic
conditions the less stable was dichloro-avobenzone (half-life 14.1 +/- 0.6 min),
while chloro-avobenzone and avobenzone were much more stable (half-lives 41 +/- 3
min and 79 +/- 13 min). Dichloroavobenzone is significantly more reactive than
avobenzone and its monochloro-derivative. On the basis of the formation of
various stable degradation products, including substituted acetophenones, benzoic
acids and phenols, identified by GC-MS, the degradation pathway has been
proposed.
PMID- 28500969
TI - Oxidation of the antibacterial agent norfloxacin during sodium hypochlorite
disinfection of marine culture water.
AB - Chlorination disinfection and antibiotic addition are two universal processes of
marine culture. The generation of disinfection byproducts (DBPs) is unavoidable.
Antibiotic residue not only pollutes water but also acts as a precursor to the
production of new DBPs. The fate of antibiotic norfloxacin (NOR) in chlorination
disinfection was investigated. It was observed that NOR could be oxidized by
disinfection agent sodium hypochlorite, but the oxidation rate varied
considerably with the type of disinfected water. For fresh water, marine culture
water and sea water, the reaction rate constant was 0.066 min-1, 0.466 min-1 and
1.241 min-1, respectively. The difference was primarily attributed to the
promotion role of bromide ions in seawater and marine culture water. Moreover,
the bromide ions could result in the generation of brominated DBPs (Br-DBPs). The
kinetics, products, reaction centers and mechanisms were investigated. The active
site of NOR was found to be the N4 atom on piperazinyl in fresh water. During
marine culture water and sea water disinfection, the carboxyl on NOR was oxidized
and two Br-DBPs were formed. This was attributed to the lowering of the
reaction's required activation energy when performed in the presence of bromide
ions. The Br-DBPs were also confirmed in real shrimp pond brackish water.
Quantitative structure activity relationships and the total organic halogen
analysis showed that the DBPs in marine culture water possessed stronger
toxicological properties than the DBPs in fresh water. The toxicity increase was
attributed to the production of Br-DBPs in the disinfection process of marine
culture water.
PMID- 28500970
TI - Histopathological changes and lipid metabolism in the liver of Bufo gargarizans
tadpoles exposed to Triclosan.
AB - In the current study, the adverse effects of TCS on liver health of B.
gargarizans tadpoles were assessed. B. gargarizans larvae were exposed to TCS at
0, 10, 30, 60, and 150 MUg L-1 from Gosner stage 3 until metamorphic climax. The
hepatosomatic index (HSI), hepatic histological and ultrastructural features, and
transcript levels of genes associated with detoxification and oxidative stress as
well as lipid metabolism in the livers were determined. Exposure to 150 MUg L-1
TCS resulted in increased HSI of tadpoles at metamorphic climax. Histological
changes characterized by an increase in the number of melanomacrophage, nucleus
pyknosis, and deposition of collagen fibers were observed in liver at 60 and 150
MUg L-1 TCS. Moreover, marked ultrastructural alterations including high electron
dense in mitochondrial matrix and lipid accumulation were also observed. In
addition, abundances of transcripts of Cu/Zn superoxide dismutase (SOD),
phospholipid hydroperoxide glutathione peroxidase (PHGPx), and heat shock protein
90 (HSP90) were decreased in larvae exposed to 60 and 150 MUg L-1 TCS, while
transcript level of HSP90 was increased at 30 MUg L-1 TCS. Also, abundances of
transcripts of acetyl-CoA carboxylase (ACC), carnitine palmitoyltransferase 2
(CPT2), peroxisome proliferator-activated receptor alpha (PPARa), fatty acid
elongase 1 (FAE), sterol carrier protein 2 (SCP) were significantly lesser in
larvae exposed to 60 and 150 MUg L-1 TCS. Overall, TCS at high levels induced
histopathological changes in the liver of B. gargarizans tadpoles. This might
have been due to the alteration of oxidative stress-related genes and lipid
metabolism-related genes expression levels.
PMID- 28500971
TI - Assessment of the oxidative and neurotoxic effects of glyphosate pesticide on the
larvae of Rhamdia quelen fish.
AB - The aim of this work was to investigate the effects of glyphosate on the
antioxidant system, as well as the neurotoxic effects on the larvae of Rhamdia
quelen. A completely randomized design was implemented with the eggs of silver
catfish distributed in 48 containers with 300 mL of water, which were subdivided
randomly into two groups: control and treated with 6.5 mg L of glyphosate. These
groups were evaluated at four time points (12 h, 24 h, 48 h, and 72 h), each with
six replications. The survival rate of eggs/larvae (%) was evaluated, and samples
were collected for antioxidant system analysis (catalase - CAT, glutathione
transferase - GST, glutathione reductase - GR, and lipoperoxidation - LPO), and
neurotoxic evaluation (cholinesterase - ChE). Throughout the 72 h of
experimentation, there was a higher survival rate among the animals treated with
glyphosate. The highest value of integrated biomarkers response (IBR = 1.26) was
at 12 h, presenting induction of the cholinesterase (ChE) enzyme and GR. At 24 h,
the value of IBR was -2.56, with inhibition of ChE and induction of GR. At 48 h,
the value was -0.76, with induction of LPO. The lowest value of IBR was at 72 h (
4.65), with induction of GST and inhibition of all other biomarkers. Finally, it
was possible to detect an acute effect of glyphosate throughout the early
development of R. quelen, with a decrease in the antioxidant system control and
neurotoxic effects.
PMID- 28500972
TI - Fate and transport of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and its
degradation products in sedimentary and volcanic rocks, Los Alamos, New Mexico.
AB - High-explosive compounds including hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX)
were used extensively in weapons research and testing at Los Alamos National
Laboratory (LANL). Liquid effluents containing RDX were released to an outfall
pond that flowed to Canon de Valle at LANL's Technical Area 16 (TA-16), resulting
in the contamination of the alluvial, intermediate and regional groundwater
bodies. Monitoring of groundwater within Canon de Valle has shown persistent RDX
in the intermediate perched zone located between 225 and 311 m below ground
surface. Monitoring data also show detectable levels of RDX putative anaerobic
degradation products. Batch and column experiments were conducted to determine
the extent of adsorption-desorption and transport of RDX and its degradation
products (MNX, DNX, and TNX) in major rock types that are within the RDX plume.
All experiments were performed in the dark using water obtained from a well
located at the center of the plume, which is fairly oxic and has a neutral pH of
7.5. Retardation factors and partitioning coefficient (Kd) values for RDX were
calculated from batch experiments. Additionally, retardation factors and Kd
values for RDX and its degradation products were calibrated from column
experiments using a one-dimensional transport model with equilibrium sorption
(linear isotherm). Results from the column and batch experiments showed little to
no sorption of RDX to the aquifer materials tested, with retardation factors
ranging from 1.0 to 1.8 and Kd values varying from 0 to 0.70 L/kg. Results also
showed no measurable differences between the transport properties of RDX and its
degradation products.
PMID- 28500973
TI - Selenate redistribution during aging in different Chinese soils and the dominant
influential factors.
AB - To date, few works have attempted to determine the effect of soil types on
Selenium aging process and the possible influential factors. In this study, the
differences in Se speciation distribution and availability in 15 Chinese typical
agricultural soils were investigated using spiked selenate for the entire year.
Results evidenced that after one year of incubation, Se transformed from soluble
fraction to Fe/Mn oxides and organic matter bound fractions in neutral or
alkaline soils (pH 7.09-8.51) and from exchangeable fraction to residual fraction
in acidic soils (pH 4.89-6.82). The available Se content in all soils declined
rapidly at the initial stage of aging, with most of the neutral or alkaline soils
reaching equilibrium after 109 d, whereas the acidic soils reached equilibrium
after only 33-56 d. The available Se content in soil decreased constantly during
the entire aging process in S4 (Xinjiang Gray desert soil), S12 (Anhui Yellow
brown earths), and S15 (Hunan Krasnozems). Elovich model was the best model (R2 >
0.80) in describing the Se aging process. Estimated time for exogenous Se
reaching the distribution of available Se in corresponding native soils extended
from 9.7 y to 50.2 y, indicating a much longer time was required for spiked soil
to reach equilibrium. Soil pH was the most significant factor directly and
negatively influencing the aging process (p < 0.05), while organic matter played
a dual role on Se speciation. Results could provide reference for the selection
of unified equilibrium time on Se-spiked experiment.
PMID- 28500974
TI - Ongoing developments in RSV prophylaxis: a clinician's analysis.
AB - Respiratory syncytial virus (RSV) is the most common respiratory pathogen in
infants and young children worldwide. Lower respiratory tract infection due to
RSV is one of the most common causes of hospitalization for infants, especially
those born premature or with chronic lung or heart disease. Furthermore, RSV
infection is an important cause of morbidity in adults, particularly in the
elderly and immunocompromised individuals. The acute phase of this infection is
often followed by episodes of wheezing that recur for months or years and usually
lead to a physician diagnosis of asthma. RSV was discovered more than 50 years
ago, and despite extensive research to identify pharmacological therapies, the
most effective management of this infection remains supportive care. The trial of
a formalin-inactivated RSV vaccine in the 1960s resulted in priming the severe
illness upon natural infection. Currently, Palivizumab is the only available
option for RSV prophylaxis, and because of restricted clinical benefits and high
costs, it has been limited to a group of high-risk infants. There are several
ongoing trials in preclinical, Phase-I, Phase-II, or Phase-III clinical stages
for RSV vaccine development based on various strategies. Here we review the
existing available prophylactic options, the current stages of RSV vaccine
clinical trials, different strategies, and major hurdles in the development of an
effective RSV vaccine.
PMID- 28500976
TI - Personality disparity in chronic regional and widespread pain.
AB - Chronic pain has high comorbidity with psychiatric disorders, therefore, better
understanding of the relationship between chronic pain and mental illness is
needed. This study aimed to investigate the pathway relationships among parental
attachment, personality characteristics, alexithymic trait and mental health in
patients with chronic widespread pain, those with chronic regional pain, and
controls. Two hundred and thirty participants were recruited. The parental
Bonding Inventory, Eysenck Personality Inventory (EPI), 20-item Toronto
Alexithymia Scale (TAS-20), Chinese Health Questionnaire, and Short-Form 36 were
filled out. The pathway relationships revealed that patients of mothers who were
more protective were more neurotic, had more difficulty identifying feelings
(DIF), worse mental health, and a higher association with chronic widespread
pain. No differences were found between patients with chronic regional pain and
the controls. The predisposing factors for chronic widespread pain, when compared
with chronic regional pain, may be more closely related to psychiatric disorders.
The pathways to chronic regional pain and chronic widespread pain differ, with
neuroticism and the alexithymic DIF trait being the main factors defining chronic
widespread pain. Therefore, besides therapies targeting pain symptoms,
psychiatric consultation, medication and psychotherapy are also recommended for
those with chronic widespread pain to alleviate their mental health conditions.
PMID- 28500977
TI - Endocytosis and intracellular traffic of cholesterol-PDMAEMA liposome complexes
in human epithelial-like cells.
AB - Liposomes are generally used as delivery systems, as they are capable of
encapsulating a wide variety of molecules (i.e. plasmids, recombinant proteins,
therapeutic drugs). However, liposomal drug delivery have to fulfill different
requirements, such as the effective internalization by the target cells and
avoidance of the degradative activity of the intracellular compartments. The use
of polymer lipid complexes (PLCs), by including different polymers in the
liposome formulation, could improve internalization and intracellular release of
drugs. The aim of the present work is to study the mechanisms of cellular
uptaking and the intracellular trafficking of PLCs formed with cholesterol-poly(2
(dimethylamino)ethyl methacrylate) CHO-PDMAEMA and lecithin (LC CHO-PD). Calcein
loaded liposomes were used to determine cellular uptake and intracellular
localization by flow cytometry and confocal microscopy. Incorporation of CHO
PDMAEMA to lecithin liposomes enhanced the internalization capacity of PLCs.
Internalization of PLCs by human epithelial-like cells (HEK-293) diminished at 4
degrees C, suggesting uptake by endocytosis. PLCs showed no co-localization with
acidic compartments after internalization. Experiments with endocytosis
inhibitors and co-localization of liposomes and albumin, suggested the caveolae
endocytic pathway as the most probable route for intracellular trafficking of
PLCs. In this work, we demonstrated an efficient uptake of LC CHO-PDs by human
epithelial-like cells (HEK-293) through the non-degradative caveolae endocytic
pathway. The mode of internalization and the intracellular fate of liposomes
under study, suggest a promising use of LC CHO-PDs as drug delivery systems.
PMID- 28500975
TI - Valnoctamide, which reduces rat brain arachidonic acid turnover, is a potential
non-teratogenic valproate substitute to treat bipolar disorder.
AB - BACKGROUND: Valproic acid (VPA), used for treating bipolar disorder (BD), is
teratogenic by inhibiting histone deacetylase. In unanaesthetized rats, chronic
VPA, like other mood stabilizers, reduces arachidonic acid (AA) turnover in brain
phospholipids, and inhibits AA activation to AA-CoA by recombinant acyl-CoA
synthetase-4 (Acsl-4) in vitro. Valnoctamide (VCD), a non-teratogenic
constitutional isomer of VPA amide, reported effective in BD, also inhibits
recombinant Acsl-4 in vitro. HYPOTHESIS: VCD like VPA will reduce brain AA
turnover in unanaesthetized rats. METHODS: A therapeutically relevant (50mg/kg
i.p.) dose of VCD or vehicle was administered daily for 30 days to male rats. AA
turnover and related parameters were determined using our kinetic model,
following intravenous [1-14C]AA in unanaesthetized rats for 10min, and measuring
labeled and unlabeled lipids in plasma and high-energy microwaved brain. RESULTS:
VCD, compared with vehicle, increased lambda, the ratio of brain AA-CoA to
unesterified plasma AA specific activities; and decreased turnover of AA in
individual and total brain phospholipids. CONCLUSIONS: VCD's ability like VPA to
reduce rat brain AA turnover and inhibit recombinant Acsl-4, and its efficacy in
BD, suggest that VCD be further considered as a non-teratogenic VPA substitute
for treating BD.
PMID- 28500978
TI - Novel polyglycerol-dioleate based cubosomal dispersion with tailored physical
characteristics for controlled delivery of ondansetron.
AB - In this study different amphiphilic lipids viz. glycerylmonooleate (GMO),
Glycerylmonolinoleate (GML), Plurol(r) (polyglycerol 3-dioleate), Soya
phosphatidylcholine (Soya PC), Dipalmitoyl-phosphatidylcholine (DPPC) and
Dipalmitoyl- phosphatidylglycerol (DPPG) were screened for their ability to form
cubosomes and the formed particles were optimized for controlled delivery using
ondansetron as a model drug. Polarized optical microscopy and high resolution
transmission electron microscopy were performed to investigate the morphology of
the prepared particles. A full factorial study was developed to optimize
formulation composition and process conditions. Atomic force microscopy and in
vitro drug release studies were done on selected formulae. Results showed that
GMO, Plurol and GML were able to form cubosomes while DPPC was able to form
spherical nanoparticles. There was a negative correlation between homogenization
speed and PS, PDI and EE%. Furthermore, there was a significant positive
correlation between Lipid: Polymer ratio and PS as well as PDI values, while
there was a slight negative correlation between it and EE% in all nanoparticles
except for those based on DPPC, which showed significant increase in EE% upon
increase in the lipid:polymer ratio. Additionally, cumulative percent release of
ondansetron from the particles shows that their design was efficiently tailored
throughout this study to afford sustained drug release with diffusion pattern.
T80 reached 19.3h in case of Plurol. Further confirmation studies on cubic
structure formation were done on selected GMO and Plurol-based nanoparticles
using scanning electron microscopy and x-ray powder diffraction. Results showed
that Plurol was able to form cubic nanostrucures resembling those formed by GMO.
Finally, Plurol (polyglyceroldioleate) showed to be a promising amphiphilic lipid
that is capable of forming cubic nanostructures like GMO opening a new era for
polyglycerols to take a step as a self assembling lipid resembling the
unsaturated monoglycerols (UMGs).
PMID- 28500979
TI - Ultra-sensitive and selective quantification of endothelin-1 in human plasma
using ultra-performance liquid chromatography coupled to tandem mass
spectrometry.
AB - Endothelin-1 (ET-1) is a potent endogenous vasoconstrictor peptide and the plasma
concentrations are commonly quantified by immunoassays such as enzyme-linked
immuno-sorbent assays (ELISA) with the disadvantage of possible cross-reactivity
with closely related endothelin derivatives. The aim of this study was to develop
and validate an ultra-sensitive and selective assay for the quantification of ET
1 in human plasma, using ultra-performance liquid chromatography with tandem mass
spectrometry (UPLC-MS/MS) after solid phase extraction. The assay fulfilled the
requirements of the US Food and Drug Administration (FDA) and the European
Medicines Agency (EMA) guidelines for assay validation, with a lower limit of
quantification of 1.5pg/mL for ET-1. Recovery rates from plasma ranged between
80.8% and 93.6%, and matrix effect varied between 121% and 135%. The assay was
successfully applied to assess the time course of plasma ET-1 concentrations in
two human volunteers after co-administration of bosentan and clarithromycin. In
this trial, the concentrations measured by UPLC-MS/MS were slightly lower than
those measured by ELISA, with a strong positive correlation between the two
methods. Our novel UPLC-MS/MS method is applicable to the clinical setting and
may have better selectivity for ET-1 than ELISA.
PMID- 28500980
TI - Serum metabolomics reveals the mechanistic role of functional foods and exercise
for obesity management in rats.
AB - Obesity is one of the independent risk factors for several health problems,
leading to metabolic perturbations and for which analytical approaches i.e.,
"metabolomics" is needed to monitor the underlying metabolic changes. In this
study, obesity associated changes were assessed via serum metabolites analysis of
obese rats fed on high fat diet. Obese rats were subsequently treated with
different functional foods used for obesity management including pomegranate,
grapefruit, and red cabbage in parallel to swimming exercise. Serum samples were
analyzed using gas chromatography-mass spectrometry (GC-MS) followed by
multivariate data analysis to classify samples and determine if such treatments
can help revert obesity related metabolic changes back to normal status. Results
led to the identification of several novel metabolites biomarkers for obesity
related to lipids, amino acids and central tricarboxylic acid (TCA) pathways.
Distinct variations in metabolite levels were recorded in obese rats compared to
normal ones including l-aspartic, l-alanine, l-glutamine, l-glycine,
phenylethanolamine, alpha-aminobutyric acid and beta-hydroxybutyric acid.
Metabolomics approach developed herein provides novel insight onto the metabolic
disturbances associated with obesity, which will assist in future drug design
that can help mitigate against such changes.
PMID- 28500981
TI - Some consequences of normal aging for generating conceptual explanations: A case
study of vitalist biology.
AB - Accumulating evidence suggests that not only diseases of old age, but also normal
aging, affect elderly adults' ability to draw on the framework theories that
structure our abstract causal-explanatory knowledge, knowledge that we use to
make sense of the world. One such framework theory, the cross-culturally
universal vitalist biology, gives meaning to the abstract concepts life and
death. Previous work shows that many elderly adults are animists, claiming that
active, moving entities such as the sun and the wind are alive (Zaitchik &
Solomon, 2008). Such responses are characteristic of young children, who, lacking
an intuitive theory of biology, distinguish animals from non-animals on the basis
of a theory of causal and intentional agency. What explains such childlike
responses? Do the elderly undergo semantic degradation of their intuitive
biological theory? Or do they merely have difficulty deploying their theory of
biology in the face of interference from the developmentally prior agency theory?
Here we develop an analytic strategy to answer this question. Using a battery of
vitalist biology tasks, this study demonstrates-for the first time-that animism
in the elderly is due to difficulty in deployment of the vitalist theory, not its
degradation. We additionally establish some powerful downstream consequences of
theory deployment difficulties, demonstrating that the elderly's use of the
agency theory is not restricted to animist judgments-rather, it pervades their
explicit reasoning about animates and inanimates. Extending the investigation, we
identify specific cognitive mechanisms implicated in adult animism, finding that
differences between young and elderly adults are mediated and moderated by
differences in inhibition and shifting mechanisms. The analytic strategy
developed here could help adjudicate between degradation and deployment in other
conceptual domains and other populations.
PMID- 28500983
TI - Night sleep influences white matter microstructure in bipolar depression.
AB - BACKGROUND: Alteration of circadian rhythms and sleep disruption are prominent
trait-like features of bipolar disorder (BD). Diffusion tensor imaging (DTI)
measures suggest a widespread alteration of white matter (WM) microstructure in
patients with BD. Sleep promotes myelination and oligodendrocyte precursor cells
proliferation. We hypothesized a possible association between DTI measures of WM
microstructure and sleep quantity measures in BD. METHODS: We studied 69
inpatients affected by a depressive episode in course of type I BD. We used whole
brain tract-based spatial statistics on DTI measures of WM microstructure: axial,
radial, and mean diffusivity (AD, RD, MD), and fractional anisotropy (FA). Self
assessed measures of time asleep (TA) and total sleep time (TST) were extracted
from the Pittsburgh Sleep Quality Index (PSQI). Actigraphic recordings were
performed on a subsample of 23 patients. RESULTS: We observed a positive
correlation of DTI measures of FA with actigraphic measures of TA and TST, and
with PSQI measure of TA. DTI measures of RD inversely associated with actigraphic
measure of TA, and with PSQI measures of TA and TST. Several WM tracts were
involved, including corpus callosum, cyngulate gyrus, uncinate fasciculus, left
superior and inferior longitudinal and fronto-occipital fasciculi, thalamic
radiation, corona radiata, retrolenticular part of internal capsule and
corticospinal tract. LIMITATIONS: The study is correlational in nature, and no
conclusion about a causal connection can be drawn. CONCLUSIONS: Reduced FA with
increased RD and MD indicate higher water diffusivity associated with less
organized myelin and/or axonal structures. Our findings suggest an association
between sleep disruption and these measures of brain microstructure in specific
tracts contributing to the functional connectivity in BD.
PMID- 28500984
TI - The need for academic electronic health record systems in nurse education.
AB - The nursing profession has been slow to incorporate information technology into
formal nurse education and practice. The aim of this study was to identify the
use of academic electronic health record systems in nurse education and to
determine student and faculty perceptions of academic electronic health record
systems in nurse education. A quantitative research design with supportive
qualitative research was used to gather information on nursing students'
perceptions and nursing faculty's perceptions of academic electronic health
record systems in nurse education. Eighty-three participants (21 nursing faculty
and 62 students), from 5 nursing schools, participated in the study. A purposive
sample of 9 nursing faculty was recruited from one university in the Midwestern
United States to provide qualitative data for the study. The researcher-designed
surveys (completed by faculty and students) were used for quantitative data
collection. Qualitative data was taken from interviews, which were transcribed
verbatim for analysis. Students and faculty agreed that academic electronic
health record systems could be useful for teaching students to think critically
about nursing documentation. Quantitative and qualitative findings revealed that
academic electronic health record systems regarding nursing documentation could
help prepare students for the future of health information technology. Meaningful
adoption of academic electronic health record systems will help in building the
undergraduate nursing students' competence in nursing documentation with
electronic health record systems.
PMID- 28500982
TI - Abnormal sleep duration associated with hastened depressive recurrence in bipolar
disorder.
AB - BACKGROUND: Abnormal sleep duration (ASD, <6 or >=9h) is common in bipolar
disorder (BD), and often persists beyond acute mood episodes. Few longitudinal
studies have examined the ASD's impact upon BD illness course. The current study
examined the longitudinal impact of ASD upon bipolar depressive
recurrence/recovery. METHODS: Outpatients referred to the Stanford BD Clinic
during 2000-2011 were assessed with the Systematic Treatment Enhancement Program
for BD (STEP-BD) Affective Disorders Evaluation at baseline, and with the
Clinical Monitoring Form at monthly follow-ups for up to two years of
naturalistic treatment. Prevalence and clinical correlates of ASD in 93 recovered
(euthymic >=8 weeks) and 153 depressed BD patients were assessed. Kaplan-Meier
analyses (Log-Rank tests) assessed relationships between baseline ASD and
longitudinal depressive severity, with Cox Proportional Hazard analyses assessing
potential mediators. RESULTS: ASD was only half as common among recovered versus
depressed BD outpatients, but was significantly associated with hastened
depressive recurrence (Log-Rank p=0.007), mediated by lifetime anxiety disorder
and attenuated by lifetime history of psychosis, and had only a non-significant
tendency towards association with delayed depressive recovery (Log-Rank p=0.07).
In both recovered and depressed BD outpatients, baseline ASD did not have
significant association with any baseline BD illness characteristic. LIMITATIONS:
Self-reported sleep duration. Limited generalizability beyond our predominately
white, female, educated, insured American BD specialty clinic sample.
CONCLUSIONS: Baseline ASD among recovered BD patients may be a risk marker for
hastened depressive recurrence, suggesting it could be an important therapeutic
target between mood episodes.
PMID- 28500985
TI - Low dose computed tomography pulmonary angiography protocol for imaging pregnant
patients: Can dose reduction be achieved without reducing image quality?
AB - OBJECTIVE: To assess the effect of low dose computed tomography pulmonary
angiography (CTPA) on radiation dose in pregnant patients. MATERIALS AND METHODS:
An old CTPA protocol for pregnant patients was compared to a new protocol.
Protocol changes included: decreased kVp; increased contrast injection rate;
imaging after shallow inspiration. Patients undergoing CTPA before (phase 1
group) or after (phase 2 group) the protocol change, were assessed. RESULTS:
Effective dose was lower in the phase 2 group (0.95 v 1.66 mSv; p<0.001).
Quantitative noise was lower in the phase 1 group (p<0.001). CONCLUSION: Low dose
CTPA tailored for pregnancy reduces dose in pregnant patients.
PMID- 28500986
TI - Intradermal invasive lobular carcinoma presenting: Not everything in the skin is
benign.
AB - In this case report, the history and imaging of two patients with invasive
lobular carcinoma (ILC) in the skin are presented, followed by a discussion of
both benign and malignant intradermal findings on breast ultrasound. Although the
majority of dermal findings are benign, these cases are a reminder that
malignancy can manifest within the skin. The purpose of presenting these cases
together is to remind breast imagers of the importance of considering malignancy
in the differential diagnosis of intradermal lesions on breast ultrasound,
especially in special circumstances such as a personal history of breast cancer
or associated clinical findings.
PMID- 28500987
TI - Optimization of NBED simulations for disc-detection measurements.
AB - Nano-beam electron diffraction (NBED) is a method which can be applied to measure
lattice strain and polarisation fields in strained layer heterostructures and
transistors. To investigate precision, accuracy and spatial resolution of such
measurements in dependence of properties of the specimen as well as electron
optical parameters, simulations of NBED patterns are required which allow to
predict the result of common disc-detection algorithms. In this paper we
demonstrate by focusing on the detection of the central disc in crystalline
silicon that such simulations require to take several experimental
characteristics into account in order to obtain results which are comparable to
those from experimental NBED patterns. These experimental characteristics are the
background intensity, the presence of Poisson noise caused by electron statistics
and blurring caused by inelastic scattering and by the transfer quality of the
microscope camera. By means of these optimized simulations, different effects of
specimen properties on disc detection - such as strain, surface morphology and
compositional changes on the nanometer scale - are investigated and discussed in
the context of misinterpretation in experimental NBED evaluations. It is shown
that changes in surface morphology and chemical composition lead to measured
shifts of the central disc in the NBED pattern of tens to hundreds of urad. These
shifts are of the same order of magnitude or even larger than shifts that could
be caused by an electric polarisation field in the range of MV/cm.
PMID- 28500988
TI - Comparison of Faradaic reactions in capacitive deionization (CDI) and membrane
capacitive deionization (MCDI) water treatment processes.
AB - Capacitive deionization (CDI) and membrane capacitive deionization (MCDI) are the
most common cell architectures in the use of CDI for water treatment. In this
work, the Faradaic reactions occurring in batch-mode CDI and MCDI processes were
compared by investigating the variation of H2O2 and dissolved oxygen (DO)
concentrations, pH, conductivity and current during charging and discharging
under different charging voltages. During charging, the H2O2 concentration in CDI
increased rapidly and then decreased while almost no H2O2 was generated in MCDI
due to the inability of oxygen to penetrate the ion exchange membrane. Chemical
kinetic models were developed to quantitatively describe the variation of H2O2
concentration and found to present satisfactory descriptions of the experimental
data. The pH drop during charging could be partially explained by Faradaic
reactions with proton generation associated with oxidation of the carbon
electrodes considered to be the major contributor. The electrode potentials
required for the induction of Faradaic reactions were analyzed with this analysis
providing robust thermodynamic explanations for the occurrence of carbon
oxidation at the anode and H2O2 generation at the cathode during the ion
adsorption process. Finally, electrochemically-induced ageing of the carbon
electrodes and the resulting performance stability were investigated. The
findings in this study contribute to a better understanding of Faradaic reactions
in CDI and MCDI and should be of value in optimizing CDI-based technologies for
particular practical applications.
PMID- 28500989
TI - Pharmaceuticals, benzene, toluene and chlorobenzene removal from contaminated
groundwater by combined UV/H2O2 photo-oxidation and aeration.
AB - This study was performed to test the feasibility of several decontamination
methods for remediating heavily contaminated groundwater in a real contaminated
locality in the Czech Republic, where a pharmaceuticals plant has been in
operation for more than 80 years. The site is polluted mainly by recalcitrant
psychopharmaceuticals and monoaromatic hydrocarbons, such as benzene, toluene and
chlorobenzene. For this purpose, an advanced oxidation technique employing UV
radiation with hydrogen peroxide dosing was employed, in combination with simple
aeration pretreatment. The results showed that UV/H2O2 was an efficient and
necessary step for degradation of the pharmaceuticals; however, the monoaromatics
were already removed during the aeration step. Characterization of the removal
mechanisms participating in the aeration revealed that volatilization, co
precipitation and biodegradation contributed to the process. These findings were
supported by bacterial metabolite analyses, phospholipid fatty acid analysis,
qPCR of representatives of the degradative genes and detailed characterization of
the formed precipitate using Mossbauer spectroscopy and scanning electron
microscopy. Further tests were carried out in a continuous arrangement directly
connected to the wells already present in the locality. The results documented
the feasibility of combination of the photo-reactor employing UV/H2O2 together
with aeration pretreatment for 4 months, where the overall decontamination
efficiency ranged from 72% to 99% of the pharmaceuticals. We recorded even better
results for the monoaromatics decontamination except for one month, when we
encountered some technical problems with the aeration pump. This demonstrated the
necessity of using the aeration step.
PMID- 28500990
TI - Evaluating the safety impact of adaptive cruise control in traffic oscillations
on freeways.
AB - Adaptive cruise control (ACC) has been considered one of the critical components
of automated driving. ACC adjusts vehicle speeds automatically by measuring the
status of the ego-vehicle and leading vehicle. Current commercial ACCs are
designed to be comfortable and convenient driving systems. Little attention is
paid to the safety impacts of ACC, especially in traffic oscillations when crash
risks are the highest. The primary objective of this study was to evaluate the
impacts of ACC parameter settings on rear-end collisions on freeways. First, the
occurrence of a rear-end collision in a stop-and-go wave was analyzed. A car
following model in an integrated ACC was developed for a simulation analysis. The
time-to-collision based factors were calculated as surrogate safety measures of
the collision risk. We also evaluated different market penetration rates
considering that the application of ACC will be a gradual process. The results
showed that the safety impacts of ACC were largely affected by the parameters.
Smaller time delays and larger time gaps improved safety performance, but
inappropriate parameter settings increased the collision risks and caused traffic
disturbances. A higher reduction of the collision risk was achieved as the ACC
vehicle penetration rate increased, especially in the initial stage with
penetration rates of less than 30%. This study also showed that in the initial
stage, the combination of ACC and a variable speed limit achieved better safety
improvements on congested freeways than each single technique.
PMID- 28500991
TI - Thermoluminescence characteristics of a chondrite (Holbrook) and an aubrite
achondrite (Norton County) meteorites.
AB - The present study constitutes the first part of a meteorite project, currently in
progress, towards the full and thorough dosimetric study (TL and OSL) of two
different meteorites of recent fall, Norton County and Holbrook. Both meteorites
exhibit strong TL sensitivity, linear dose response and no saturation for doses
up to 2kGy. However, the two meteorites exhibited a very dissimilar TL glow curve
and behaviour regarding sensitization and fading. Notably, the Norton County
aubrite achondrite was found to exhibit a strong fading of the high-temperature
peak (~300 degrees C), attributed to anomalous fading, whereas Holbrook did not
seem to show signs of anomalous fading. Since quantitative conclusions regarding
the thermal and irradiation history of meteorites, require knowledge of the
detailed peak structure of the glow curve and deeper understanding of the
trapping mechanism, the glow curves, after irradiation in the range 10-2000Gy,
were deconvoluted using general order kinetics. The fitting parameters extracted
point towards complex non-strictly first order mechanisms with a multitude of
traps acting very differently. All the above, combined with future OSL
measurements, currently in progress, are expected to shed light on the nature of
the involved traps in both phenomena (energy depth, light-resistance etc), which
would allow to extract more concrete conclusions about their history.
PMID- 28500993
TI - Nonsynonymous changes of equine lentivirus receptor-1 (ELR1) gene in amino acids
involved in the interaction with equine infectious anemia virus (EIAV).
AB - Equine lentivirus receptor-1 (ELR1) has been characterized as the specific
functional receptor that mediates equine infectious anemia virus (EIAV) entrance
to horse macrophages. This receptor is tumor necrosis factor receptor superfamily
member 14 (TNFRSF14). The aim of this study was to investigate the occurrence of
allelic variants in the coding sequence of equine TNFRSF14 gene by screening for
single-nucleotide polymorphisms (SNPs) in different equine populations. Forty
seven horse samples were randomly selected from a reservoir of EIAV-seropositive
and seronegative samples collected from different outbreaks and regions of
Argentina. DNA samples were scanned via PCR and direct sequencing of exon 3 and
exon 5 of TNFRSF14 gene. A total of 21 SNPs were identified, of which 11 were
located in coding sequences. Within exon 5, four SNPs caused nonsynonymous
substitutions, while two other SNPs caused synonymous substitutions in crucial
residues (Ser112 and Thr114) implicated in the interaction with EIAV. Despite
some of exon 5 variants occurred exclusively in EIAV-positive or EIAV-negative
horses, critical residues for the function of the mature protein were conserved,
accounting for selective pressures in favor of preserving the specific function
of TNFRSF members and the host immune response. To our knowledge, this is the
first report of the existence of allelic variations involving some crucial amino
acid residues in horse ELR1. Further, it could be an initial step to test the
possible functional relevance and relationship of these variants with EIAV
infection and disease progression as well as to develop preventive strategies.
PMID- 28500992
TI - Multi-transmitter neurons in the mammalian central nervous system.
AB - It is firmly established that many mammalian neurons release various combinations
of amino acids, their derivatives, and other small molecules from presynaptic
terminals in order to signal to their postsynaptic targets. Here we discuss
recent findings about four types of multi-transmitter neurons-those that release
GABA and acetylcholine (Ach); dopamine (DA) and GABA or glutamate; and glutamate
and GABA. The mechanisms of co-release in each class differ and highlight the
complex and dynamic nature of neurotransmitter release. Furthermore, identifying
the neurotransmitter signature of each neuron and the post-synaptic targets of
each neurotransmitter remain challenging. The existence of multi-transmitter
neurons complicates the interpretation of connectomic wiring diagrams and poses
interesting challenges for our understanding of circuit function in the brain.
PMID- 28500994
TI - Salt-tolerance mechanisms induced in Stevia rebaudiana Bertoni: Effects on
mineral nutrition, antioxidative metabolism and steviol glycoside content.
AB - In order to cope with challenges linked to climate change such as salinity,
plants must develop a wide spectrum of physiological and molecular mechanisms to
rapidly adapt. Stevia rebaudiana Bertoni plants are a case in point. According to
our findings, salt stress has no significant effect on plant growth in these
plants, which accumulate sodium (Na+) in their roots, thus avoiding excessive Na+
accumulation in leaves. Furthermore, salt stress (NaCl stress) increases the
potassium (K+), calcium (Ca2+), chloride ion (Cl-) and proline concentrations in
Stevia leaves, which could contribute to osmotic adjustment. We also found that
long-term NaCl stress does not produce changes in chlorophyll concentrations in
Stevia leaves, reflecting a mechanism to protect the photosynthesis process.
Interestingly, an increase in chlorophyll b (Chlb) content occured in the oldest
plants studied. In addition, we found that NaCl induced reactive oxygen species
(ROS) accumulation in Stevia leaves and that this accumulation was more evident
in the presence of 5 g/L NaCl, the highest concentration used in the study.
Nevertheless, Stevia plants are able to induce (16 d) or maintain (25 d)
antioxidant enzymes to cope with NaCl-induced oxidative stress. Low salt levels
did not affect steviolbioside and rebaudioside A contents. Our results suggest
that Stevia plants induce tolerance mechanisms in order to minimize the
deleterious effects of salt stress. We can thus conclude that saline waters can
be used to grow Stevia plants and for Steviol glycosides (SGs) production.
PMID- 28500995
TI - Antibacterial activity and mechanism of action of the benzazole acrylonitrile
based compounds: In vitro, spectroscopic, and docking studies.
AB - A new series of pyrimidine derivatives 5, 9a-d and 12a-d was synthesized by an
efficient procedure. The antibacterial activity of the new compounds was studied
against four bacterial strains. Compound 5 was found to exhibit the highest
potency, with = 1.0 MUg/ml, against both Escherichia coli and Pseudomonas
aeruginosa when compared with amoxicillin (MIC = 1.0-1.5 MUg/mL). Transmission
electron microscope results confirmed that activities against bacteria occurred
via rupturing of the cell wall. Molecular modeling results suggested that
compounds 5, 9a-d and 12a-d have the potential to irreversibly bind to the
penicillin-binding protein (PBP) Ser62 residue in the active site and were able
to overcome amoxicillin resistance in bacteria by inhibiting the beta-lactamase
enzyme. Docking studies showed that compounds 5, 9a-d and 12a-d inhibit the beta
lactamase enzyme through covalent bonding with Ser70. The synergistic effect with
amoxicillin was studied. The newly synthesized compounds reported in this study
warrant further consideration as prospective antimicrobial agents.
PMID- 28500996
TI - Professor Kerstin Hall (1929-1917): Pioneer in the field of growth hormone and
IGF research.
PMID- 28500997
TI - Does a policy of earlier induction affect labour outcomes in women induced for
postmaturity? A retrospective analysis in a tertiary hospital in the North of
England.
AB - OBJECTIVES: to investigate whether a change in the management of postmature
pregnancy to earlier induction affects the length of labour and the induction
process. Secondly, to assess the feasibility of the research process to inform a
future larger study. DESIGN: a change in management of postmature pregnancy in an
NHS hospital in October 2013, from induction at 42 weeks gestation to induction
between 41-42 weeks, provided an opportunity to conduct a retrospective analysis.
Pre-existing data from the maternity database and casenotes were collected and
primary outcomes analysed using the Mann-Whitney test and the Hodges-Lehman
confidence interval for differences in medians. SETTING: a large city based
tertiary referral hospital in the North of England. PARTICIPANTS: 125 women
induced before the change in policy were compared with 309 women induced after
the change. MEASUREMENTS: primary outcomes were length of 1st and 2nd stage of
labour, overall length of labour, length of induction to established labour and
length of induction to birth. FINDINGS: the median overall length of labour for
women induced at 42 weeks was 6.5hours, while for women induced at 41-42 weeks
this was 5.2hours. The difference was not statistically significant (p=0.15, 95%
CI for median difference -0.27 to 1.93hours) with a small effect size (Pearson's
r=-0.08). The median length of induction to birth was 13.6hours for women induced
at 42 weeks and 16.5hours for women induced at 41-42 weeks. This difference was
also not statistically significant (p=0.14, 95% CI for median difference -7.25 to
1.20hours) with a small effect size (Pearson's r=-0.13). KEY CONCLUSIONS AND
IMPLICATIONS FOR PRACTICE: This study demonstrated no statistically significant
differences in length of labour and induction following a change in the
management of postmature pregnancy to earlier induction. A large study is needed
to establish definitively the effects of earlier induction on labour outcomes.
PMID- 28500998
TI - The impact of surface and geometry on coefficient of friction of artificial hip
joints.
AB - Coefficient of friction (COF) tests were conducted on 28-mm and 36-mm-diameter
hip joint prostheses for four different material combinations, with or without
the presence of Ultra High Molecular Weight Polyethylene (UHMWPE) particles using
a novel pendulum hip simulator. The effects of three micro dimpled arrays on
femoral head against a polyethylene and a metallic cup were also investigated.
Clearance played a vital role in the COF of ceramic on polyethylene and ceramic
on ceramic artificial hip joints. Micro dimpled metallic femoral heads yielded
higher COF against a polyethylene cup; however, with metal on metal prostheses
the dimpled arrays significantly reduced the COF. In situ images revealed
evidence that the dimple arrays enhanced film formation, which was the main
mechanism that contributed to reduced friction.
PMID- 28500999
TI - Effects of working gas pressure on zirconium dioxide thin film prepared by pulsed
plasma deposition: roughness, wettability, friction and wear characteristics.
AB - In joint arthroplasty one of the main issues related to the failure of prosthetic
implants is due to the wear of the ultra-high molecular weight polyethylene
(UHMWPE) component. Surface treatments and coatings have been recognized as
enhancing methods, able to improve the tribological properties of the implants.
Therefore, the main objective of this work was to investigate the possibility to
fabricate yttria-stabilized zirconia (YSZ) coatings on a metal (AISI 316-L)
substrate by means of Pulsed Electron Deposition, in order to improve the
tribological behavior of the polymer-metal coupling, by reducing the initial wear
of the UHMWPE component. In order to optimize the coating characteristics, the
effects of working gas pressure on both its morphological and tribological
properties were analyzed. Morphological characterization of the films was
evaluated by Atomic Force Microscopy (AFM). Coating wettability was also
estimated by contact angle (CA) measurement. Tribological performance (coupling
friction and wear of UHMWPE) was evaluated by using a ball-on-disc tribometer
during highly-stressing tests in dry and lubricated (i.e. NaCl and serum)
conditions; friction and wear were specifically evaluated at the initial sliding
distances - to highlight the main effect of coating morphology - and after 100m -
where the influence of the intrinsic materials properties prevails. AFM analysis
highlighted that the working pressure heavily affected the morphological
characteristics of the realized films. The wettability of the coating at the
highest and lowest deposition pressures (CA ~ 60 degrees , closed to substrate
value) decreased for intermediate pressures, reaching a maximum CA of ~ 90
degrees . Regarding tribological tests, a strong correlation was found in the
initial steps between friction coefficient and wettability, which decreased as
the distance increased. Concerning UHMWPE wear associated to coated counterpart,
at 100m a reduction rate of about 7% in dry, 12% in NaCl and 5% in presence of
serum was obtained compared to the uncoated counterpart. Differently from what
highlighted for friction, no correlation was found between wear rate and
morphological parameters. These findings, in agreement with literature,
underlined the effect of the deposition pressure on the morphological properties,
but suggested that physical characteristics are influenced too. Further research
on the deposition process will be required in order to improve the tribological
performance of the coating at long distances, addressing - above all - orthopedic
applications.
PMID- 28501000
TI - Combination of a biodegradable three-dimensional (3D) - printed cage for
mechanical support and nanofibrous membranes for sustainable release of
antimicrobial agents for treating the femoral metaphyseal comminuted fracture.
AB - The aim of this study was to develop a biodegradable three-dimensional-printed
polylactide (PLA) cage for promoting bony fixation and an antibiotics-embedded
poly(d,l)-lactide-co-glycolide (PLGA) nanofibrous membrane for infectious
prophylaxis during treating the comminuted metaphyseal fracture in a rabbit
femoral model. The in vitro studies included measuring the mechanical properties
of the 3D printed cage and determining release activities of vancomycin and
ceftazidime from the nanofibers. The in vivo study included comparisons of
rabbits of the femoral metaphyseal comminuted fracture treated with or without
the combined biodegradable polymers. The results showed that vancomycin and
ceftazidime were sustainably detected above the effective levels in the local
tissue fluid around the fracture site for 3 weeks. The animal studies showed that
rabbits with the 3D cage implantation possessed better cortical integrity, leg
length ratio, and maximal bending strengths. The study results indicate that
these combined polymers may promote fracture fixation during treating the rabbit
femoral metaphyseal comminuted fracture.
PMID- 28501001
TI - One-pot chemo-enzymatic synthesis of furfuralcohol from xylose.
AB - Furfuralcohol (FOL) is an important intermediate for the production of lysine,
ascorbic acid, and lubricants. It can be used as a hypergolic fuel in rocketry.
In this study, it was attempted to synthesize FOL from xylose by tandem catalysis
with solid acid SO42-/SnO2-Montmorillonite and recombination Escherichia coli
CCZU-K14 whole cells. Using SO42-/SnO2-Montmorillonite (3.0wt% dosage) as
catalyst, a highest furfural yield of 41.9% was achieved from xylose at 170
degrees C for 20min. Furthermore, Escherichia coli CCZU-K14 whole cells were used
for bioconverting furfural to FOL. The optimum biocatalytic reaction temperature,
reaction pH, cosubstrate concentration, and substrate concentration were 30
degrees C, 6.5, 1.5mol glucose/mol furfural, and 200mM, respectively. Finally,
the yield of FOL from 200mM furfural was achieved to 100% by Escherichia coli
CCZU-K14 whole cells after 24h. In conclusion, this strategy show high potential
application for the effective synthesis of FOL.
PMID- 28501002
TI - Effects of lactic acid bacteria and molasses additives on the microbial community
and fermentation quality of soybean silage.
AB - The objective was to study effects of lactic acid bacteria (L) and molasses (M)
on the microbial community and fermentation quality of soybean silage. Soybean
was ensiled with no additive control (C), 0.5% molasses (0.5%M), 0.5%M+L
(0.5%ML), 2%M, 2%M+L (2%ML) for 7, 14, 30 and 60days. The M-treated silages could
increase the content of lactic acid and decrease butyric acid than control.
Besides, higher crude protein was also observed in M-treated silages. With
prolonged ensiling time, there was a reduction of the ratio of lactic acid/acetic
acid in the 2%M-treated and 2%ML-treated silages. The combined addition of L and
2%M could enhance the account of desirable Lactobacillus and inhibit the growth
of undesirable microorganism such as Clostridia and Enterobacter. In summary, the
silage quality of soybean was improved with the addition of L and M.
PMID- 28501003
TI - Phytochemicals for taming agitated immune-endocrine-neural axis.
AB - Homeostasis of immune-endocrine-neural axis is paramount for human health. If
this axis gets agitated due to age, genetic variations, environmental exposures
or lifestyle assaults, a cascade of adverse reactions occurs in human body.
Cytokines, hormones and neurotransmitters, the effector molecules of this axis
behave erratically, leading to a gamut of neural, endocrine, autoimmune, and
metabolic diseases. Current panel of drugs can tackle some of them but not in a
sustainable, benign way as a myriad of side effects, causal of them have been
documented. In this context, phytochemicals, the secondary metabolites of plants
seem beneficial. These bioactive constituents encompassing polyphenols,
alkaloids, flavonoids, terpenoids, tannins, lignans, stilbenoids (resveratrol),
saponins, polysaccharides, glycosides, and lectins etc. have been proven to exert
antioxidant, anti-inflammatory, hypolipidemic, hypotensive, antidiabetic,
anticancer, immunomodulatory, anti-allergic, analgesic, hepatoprotective,
neuroprotective, dermatoprotective, and antimicrobial properties, among a litany
of other biological effects. This review presents a holistic perspective of
common afflictions resultant of immune-endocrine-neural axis disruption, and the
phytochemicals capable of restoring their normalcy and mitigating the ailments.
PMID- 28501004
TI - Adipose-derived mesenchymal stem cells slow disease progression of acute-on
chronic liver failure.
AB - A serious complication of chronic hepatic insufficiency is acute-on-chronic liver
failure, a recognized syndrome characterized by acute decompensation of cirrhosis
and organ/system failure. We investigated the use of adipose-derived mesenchymal
stem cells (AD-MSCs) in an experimental model of acute-on-chronic liver failure,
developed by microsurgical extrahepatic cholestasis in rats. Rats undergoing
microsurgical extrahepatic cholestasis were treated by intraparenchymal liver
injection of human or rat AD-MSCs, undifferentiated or previously differentiated
in vitro toward the hepatocyte lineage. The groups treated with rat AD-MSCs
showed less ascites, lower hepato- and splenomegaly, less testicular atrophy, and
an improvement in serum biochemical hepatic parameters. There was also an
improvement in histological liver changes, in which the area of fibrosis and bile
duct proliferation were significantly decreased in the group treated with
predifferentiated rat AD-MSCs. In conclusion, an isograft of hepatocyte
predifferentiated AD-MSCs injected intraparenchymally 2 weeks after microsurgery
in extrahepatic cholestatic rats prevents secondary complications of acute-on
chronic hepatic failure. These data support the potential use of autologous AD
MSCs in the treatment of human cholestasis, and specifically of newborn biliary
atresia, which could be beneficial for patients awaiting transplant.
PMID- 28501005
TI - HuR promotes breast cancer cell proliferation and survival via binding to CDK3
mRNA.
AB - HuR, a ubiquitously expressed RNA-binding protein, stabilizes mRNA and regulates
its translation. HuR expression was increased at all stages of breast cancer and
correlated with poor clinical outcome. However, the detailed mechanisms remain
unclear. Here we reported that overexpression of HuR increased CDK3 mRNA
stability and thus its protein expression in MDA-MB-231 and MCF-7 cells.
Mechanistically, CDK3 mRNA was identified as a target of HuR via bioinformatics
and RNA binding protein immunoprecipitation (RIP) assays. Furthermore, treatment
with HuR shRNA decreased CDK3 expression, inhibited cell proliferation and
promoted cell apoptosis in breast cancer. More importantly, overexpression of
CDK3 reversed the suppressive effects of HuR knockdown on cell growth in both MDA
MB-231 and MCF-7 cells. Finally, HuR and CDK3 expression levels were positively
correlated and significantly up-regulated in breast cancer samples. And
overexpression of HuR attenuated the chemotherapeutical efficiency of breast
cancer. Therefore, our results indicate that ectopic expression of HuR promotes
breast cancer cell proliferation and survival by directly binding to and
stabilizing CDK3 mRNA.
PMID- 28501006
TI - Liquid chromatography-mass spectrometry-based quantitative proteomics analysis
reveals chondroprotective effects of astragaloside IV in interleukin-1beta
induced SW1353 chondrocyte-like cells.
AB - OBJECTIVE: Chondrocyte apoptosis played a key role on the progression of
Osteoarthritis (OA). Safe and effective drugs are urgently needed for the
treatment of OA. Previous study reported that Astragaloside IV (ASG-IV) had
exerted a protective effect against articular cartilage degeneration by promoting
rapid proliferation of chondrocyte. Therefore, the aim of our study is to explore
the effects and mechanisms of ASG-IV in chondrocyte apoptosis. METHODS: Isobaric
Tags For Relative And Absolute Quantitation (iTRAQ)-based quantitative proteomics
was used to quantitatively detect and map proteins in SW1353 chondrocyte-like
cells pre-treated with ASG-IV or interleukin-1beta (IL-1beta) or ASG-IV+IL-1beta.
The iTRAQ-labeled peptides were fractionated by high-accuracy liquid
chromatography-mass spectrometry (LC-MS). Cell apoptosis and differentially
expressed proteins was detected by flow cytometry (FCM), quantitative real-time
polymerase chain reaction (qRT-PCR), and western blotting, respectively. RESULTS:
The apoptosis of the IL-1beta-induced SW1353 cells treated with ASG-IV was
greatly inhibited. Bioinformatics analysis revealed that gamma actin 1 (ACTG1)
and Yes Associated Protein 1 (YAP1), participating in the Hippo signaling pathway
and Vitronectin (VTN) and Collagen Type I Alpha 1 Chain (COL1A1), involving in
the extracellular matrix (ECM)-receptor interaction signaling pathway, were all
significantly up-regulated in the IL-1beta-induced SW1353 cells after treatment
with ASG-IV. The qRT-PCR and Western blotting results confirmed the up-regulation
of these four genes. CONCLUSION: ASG-IV played a positive role in human
osteoarthritic chondrocyte apoptosis, possibly through modulation of the Hippo
signaling pathway by up-regulating YAP1and ACTG1 expression, and also by up
regulating VTN and COL1A1, which are involved in the ECM-receptor interaction
pathway. Taken together, all the results suggested that ASG-IV had a novel
therapeutic potential for the treatment of OA.
PMID- 28501007
TI - MiR-330 inhibits IL-22-induced keratinocyte proliferation through targeting
CTNNB1.
AB - Psoriasis is a common chronic inflammatory skin disease which is characterized by
hyperproliferation and aberrant differentiation of keratinocytes; however the
exact pathogenesis is largely unknown. Interleukin-22 (IL-22) has demonstrated
its vital role in T cell-mediated immune response by interacting with
keratinocytes in the pathogenesis of psoriasis. The microRNAs (miRNAs) are a
class of small non-coding RNA molecules that play important roles in cellular
processes by regulating gene expression at the post-transcriptional level. MiR
330 has been reported to inhibit the proliferation and migration of mouse
keratinocytes. In the present study, we indicated that miR-330 expression in
lesion tissue of psoriasis patients was specifically down-regulated, and could
inhibit IL-22-induced proliferation of HaCaT and HKC cell. Wnt/beta-catenin
pathway plays an essential role in the pathogenesis of psoriasis. By direct
targeting CTNNB1, miR-330 could significantly downregulate IL-22-induced CTNNB1
expression. In addition, we found that the downstream targets of beta-catenin,
CyclinD1 and Axin2, could be affected by miR-330; miR-330 could suppress CyclinD1
protein expression and rescue Axin2 protein expression. Taken together, we
indicated miR-330 inhibits IL-22-induced proliferation of HaCaT and HKC cell by
targeting CTNNB1 and subsequently affect the downstream factors, CyclinD1 and
Axin2 for the first time, and provide diagnostic markers and a novel target for
psoriasis treatment.
PMID- 28501009
TI - miR-205 as a biological marker in non-small cell lung cancer.
AB - OBJECTION: The aim of this study is to explain the significance and mechanism of
miR-205 in the diagnosis and treatment of non-small cell lung cancer. METHODS:
The 70 advanced NSCLC patients, treated in our hospital, were collected from
2011.10 to 2013.9, taking the tissues from cancer and adjacent tissues to measure
the miR-205 expression, evaluate the AKT gene and protein expression of cancer
and adjacent normal tissues by RT-PCR and Immunohistochemistry (IHC) assays and
analyzing the correlation between miR-205 and AKT. Following up the patients for
2 years; Recording patients' survival time. In the cell experiment, Selecting
A549 cell as research object, the cells were divided into three groups: Normal
control group (NC), Blank control group (BL) and si-miR-205 transfection group
(si-miR-205). Cell proliferation rate and apoptosis rate were detected by MTT
method and flow cytometry; Measuring invasion and migration of difference groups
by transwell and scratch testing, measured the Akt, mTOR,P21, MMP2 and MMP9 gene
expression and detected Akt, p-Akt, mTOR, p-mTOR, P21, MMP2 and MMP 9 protein
expression levels. RESULTS: Compared with adjacent normal tissue, the miR-205 and
AKT gene expression level was significantly increased in NSCLC tissues (P<0.05)
and the AKT protein expression was stronger than that of healthy tissues, miR-205
was positive correlation with AKT; In the overall survival, MiR-205 high
expression group was significantly higher than low expression group (P<0.05). In
the cell experiment, Compared with NC and BL groups, si-miR-205 could
significantly reduced the biological activity of A549 cells in proliferation,
invasion and migration, and promoted the apoptosis of A549 cells (P<0.05,
respectively). Akt, p-Akt, mTOR, p-mTOR, P21, MMP 2 and MMP 9 gene and protein
expression of si-miR-205 group were significantly compared with NC and BL groups
(P<0.05, respectively). CONCLUSION: miRNA-205 might serve as a potential
biomarker for the prognosis of advanced NSCLC, and inhibiting miR-205 expression
could decrease A549 cells biological activity by regulating Akt/mTOR/P21 and
Akt/MMP 2/MMP 9signaling pathway.
PMID- 28501008
TI - Ethanol extract and its dichloromethane fraction of Alpinia oxyphylla Miquel
exhibited hepatoprotective effects against CCl4-induced oxidative damage in vitro
and in vivo with the involvement of Nrf2.
AB - Alpinia oxyphylla Miq. (A. oxyphylla), as a kind of medicine which also be used
as food, is widely used in East Asian for the treatment of dyspepsia, diarrhea,
abdominal pain and deficiency cold of spleen and stomach. This study aimed to
investigate the protective effects of ethanol extract (EE) and its
dichloromethane fraction (DM) of A. oxyphylla, which are rich in phenolic
compounds, against CCl4-induced hepatic injury in vitro and in vivo. EE, DM and
silymarin ameliorated CCl4-induced decrease of cell viability and increase of
reactive oxygen species (ROS) in HepG2 cells. The CCl4-induced changes of
glutathione (GSH) and methane dicarboxylic aldehyde (MDA) levels, and the
decrease of superoxide dismutase (SOD) and catalase (CAT) activities were all
restored with the pretreatment of EE, DM and silymarin. The results in liver
injury model in rats showed that EE, DM and silymarin could significant decrease
the levels of serum aspartate aminotransferase (AST), alanine aminotransferase
(ALT), alkaline phosphatase (ALP) and total bilirubin than the model group. Liver
histopathology revealed that EE and DM attenuated the incidence of liver lesions
triggered by CCl4 intoxication. They also effectively relieved CCl4-induced
oxidative damage. Western blot analysis indicated NF-E2-related factor (Nrf2)
pathway played an critical role in the protection of EE and DM against CCl4
induced oxidative stress. In conclusion, the extracts from A. oxyphylla might be
used as hepatoprotective agents.
PMID- 28501010
TI - Detecting and predicting the impact of land use changes on groundwater quality, a
case study in Northern Kelantan, Malaysia.
AB - The conversions of forests and grass land to urban and farmland has exerted
significant changes on terrestrial ecosystems. However, quantifying how these
changes can affect the quality of water resources is still a challenge for
hydrologists. Nitrate concentrations can be applied as an indicator to trace the
link between land use changes and groundwater quality due to their solubility and
easy transport from their source to the groundwater. In this study, 25year
records (from 1989 to 2014) of nitrate concentrations are applied to show the
impact of land use changes on the quality of groundwater in Northern Kelantan,
Malaysia, where large scale deforestation in recent decades has occurred. The
results from the integration of time series analysis and geospatial modelling
revealed that nitrate (NO3-N) concentrations significantly increased with
approximately 8.1% and 3.89% annually in agricultural and residential wells,
respectively, over 25years. In 1989 only 1% of the total area had a nitrate value
greater than 10mg/L; and this value increased sharply to 48% by 2014. The
significant increase in nitrate was only observed in a shallow aquifer with a
3.74% annual nitrate increase. Based on the result of the Autoregressive
Integrated Moving Average (ARIMA) model the nitrate contamination is expected to
continue to rise by about 2.64% and 3.9% annually until 2030 in agricultural and
residential areas. The present study develops techniques for detecting and
predicting the impact of land use changes on environmental parameters as an
essential step in land and water resource management strategy development.
PMID- 28501011
TI - Public health and economic risk assessment of waterborne contaminants and
pathogens in Finland.
AB - This study shows that a variety of mathematical modeling techniques can be
applied in a comprehensive assessment of the risks involved in drinking water
production. In order to track the effects from water sources to the end
consumers, we employed four models from different fields of study. First, two
models of the physical environment, which track the movement of harmful
substances from the sources to the water distribution. Second, a statistical
quantitative microbial risk assessment (QMRA) to assess the public health risks
of the consumption of such water. Finally, a regional computable general
equilibrium (CGE) model to assess the economic effects of increased illnesses. In
order to substantiate our analysis, we used an illustrative case of a recently
built artificial recharge system in Southern Finland that provides water for a
300,000 inhabitant area. We examine the effects of various chemicals and microbes
separately. Our economic calculations allow for direct effects on labor
productivity due to absenteeism, increased health care expenditures and indirect
effects for local businesses. We found that even a considerable risk has no
notable threat to public health and thus barely measurable economic consequences.
Any epidemic is likely to spread widely in the urban setting we examined, but is
also going to be short-lived in both public health and economic terms. Our
estimate for the ratio of total and direct effects is 1.4, which indicates the
importance of general equilibrium effects. Furthermore, the total welfare loss is
2.4 times higher than the initial productivity loss. The major remaining
uncertainty in the economic assessment is the indirect effects.
PMID- 28501012
TI - Alkylphenol and phthalate contamination of all sources of greywater from French
households.
AB - Despite the importance of domestic wastewater, the contribution of greywater to
both alkylphenol and phthalate pollution is not yet well documented. Likewise,
the detailed emissions of phthalates and alkylphenols by greywater have been
insufficiently studied, this work aims to fill this gap. The levels of four
phthalates (DEP, DnBP, BBP and DEHP) and two alkylphenols (nonylphenol isomers
and octylphenol) were quantified in six different types of greywater, namely that
from washing machines, manual dishwashing, dishwashers, bathroom water (from
showers and sinks) and floor cleaning. This paper presents the methodology used
to characterize all sources of greywater and provides their levels of
contamination. The highest concentrations were found in greywater produced by the
washing machine and floor cleaning, while washing machine and shower greywater
have the highest phthalate and alkylphenol loads because of the volume associated
with these two sources of greywater.
PMID- 28501013
TI - Comparison of surface energy budgets and feedbacks to microclimate among
different land use types in an agro-pastoral ecotone of northern China.
AB - The biophysical effect of land use conversion plays a significant role in
regulating climate change. Owing to albedo and evapotranspiration (ET) change,
the effect of energy budget difference on land surface temperature (LST) is
important but unclear among contrasting land use types, especially in temperate
semi-arid regions. Based on moderate-resolution imaging spectroradiometer (MODIS)
data, we compared the differences in albedo, ET, and LST between cropland and
grassland (CR-GR), and between planted forest and grassland (PF-GR) in the Horqin
Sandy Land of Inner Mongolia, an agro-pastoral ecotone of northern China. Our
main objective was to explore the magnitude and direction of albedo and ET change
during the growing season and, subsequently, to estimate the biophysical effects
on LST as a result of land use and land cover change. Our results indicate no
significant difference in mean monthly albedo for CR-GR and PF-GR. Cropland lost
more water through ET and significantly decreased daytime LST compared with
grassland from July to September, but no significant differences in ET and LST
were observed for PF-GR in any month. The biophysical climate effects were more
pronounced for CR-GR compared with PF-GR. The response of LST to the changes in
energy budget confirmed that ET was the critical driving factor relative to
albedo. Compared with grassland, cropland and planted forest tended to cool the
land surface by 5.15 degrees C and 1.51 degrees C during the growing season,
respectively, because of the biophysical effects. Our findings suggest the
significance of local-scale biophysical effect on climate variation after land
use conversion in semi-arid regions.
PMID- 28501014
TI - Discrimination between acute and chronic decline of Central European forests
using map algebra of the growth condition and forest biomass fuzzy sets: A case
study.
AB - Forest decline is either caused by damage or else by vulnerability due to
unfavourable growth conditions or due to unnatural silvicultural systems. Here,
we assess forest decline in the Czech Republic (Central Europe) using fuzzy
functions, fuzzy sets and fuzzy rating of ecosystem properties over a 1*1km grid.
The model was divided into fuzzy functions of the abiotic predictors of growth
conditions (Fpred including temperature, precipitation, acid deposition, soil
data and relative site insolation) and forest biomass receptors (Frec including
remote sensing data, density and volume of aboveground biomass, and surface humus
chemical data). Fuzzy functions were designed at the limits of unfavourable,
undetermined or favourable effects on the forest ecosystem health status. Fuzzy
sets were distinguished through similarity in a particular membership of the
properties at the limits of the forest status margins. Fuzzy rating was obtained
from the least difference of Fpred-Frec. Unfavourable Fpred within unfavourable
Frec indicated chronic damage, favourable Fpred within unfavourable Frec
indicated acute damage, and unfavourable Fpred within favourable Frec indicated
vulnerability. The model in the 1*1km grid was validated through spatial
intersection with a point field of uniform forest stands. Favourable status was
characterised by soil base saturation (BS)>50%, BCC/Al>1, Corg>1%, MgO>6g/kg, and
nitrogen deposition<1200mol(H+)/ha.year. Vulnerable forests had BShumus 46-60%,
BCC/Al 9-20 and NDVI~0.42. Chronic forest damage occurs in areas with low
temperatures, high nitrogen deposition, and low soil BS and Corg levels. In the
Czech Republic, 10% of forests were considered non-damaged and 77% vulnerable,
with damage considered acute in 7% of forests and chronic in 5%. The fuzzy model
used suggests that improvement in forest health will depend on decreasing
environmental load and restoration concordance between growth conditions and tree
species composition.
PMID- 28501015
TI - Effect of medium-pressure UV-lamp treatment on disinfection by-products in
chlorinated seawater swimming pool waters.
AB - Several brominated disinfection by-products (DBPs) are formed in chlorinated
seawater pools, due to the high concentration of bromide in seawater. UV
irradiation is increasingly employed in freshwater pools, because UV treatment
photodegrades harmful chloramines. However, in freshwater pools it has been
reported that post-UV chlorination promotes the formation of other DBPs. To date,
UV-based processes have not been investigated for DBPs in seawater pools. In this
study, the effects of UV, followed by chlorination, on the concentration of three
groups of DBPs were investigated in laboratory batch experiments using a medium
pressure UV lamp. Chlorine consumption increased following post-UV chlorination,
most likely because UV irradiation degraded organic matter in the pool samples to
more chlorine-reactive organic matter. Haloacetic acid (HAA) concentrations
decreased significantly, due to photo-degradation, but the concentrations of
trihalomethanes (THMs) and haloacetonitriles (HANs) increased with post-UV
chlorination. Bromine incorporation in HAAs was significantly higher in the
control samples chlorinated without UV irradiation but decreased significantly
with UV treatment. Bromine incorporation was promoted in THM and HAN after UV and
chlorine treatment. Overall, the accumulated bromine incorporation level in DBPs
remained essentially unchanged in comparison with the control samples. Toxicity
estimates increased with single-dose UV and chlorination, mainly due to increased
HAN concentrations. However, brominated HANs are known in the literature to
degrade following further UV treatment.
PMID- 28501016
TI - Role of climate anomalies on decadal variation in the occurrence of wintertime
haze in the Yangtze River Delta, China.
AB - The wintertime haze day (HD) in the Yangtze River Delta (YRD) region of China
shows a significant upward trend during the past decades due to the rapid
industrialization and urbanization. Besides the enhanced anthropogenic emission,
climate change also plays the important role in the long term HD variations. In
this study, the significant decadal variation of wintertime HD during the period
1960-2012 in YRD is examined by the empirical orthogonal function (EOF) analysis,
featured as less HD occurrence before 1980 and more occurrence after 2000. The
numerical simulations by the global transport and chemical model (Model for Ozone
and Related chemical Tracers, MOZART) with the same emission inventory suggest
8.4% enhancement of wintertime PM2.5 (particulate matter with the equivalent
diameter of air dynamics less than or equal to 2.5MUm) mass concentration in YRD
during 2001-2009 compared with that during 1971-1979 attributed to meteorological
changes, indicating the significant effect of climate anomaly on the decadal
variations of wintertime HD. Through the composite analysis on the atmospheric
dynamical and thermal conditions based on the reanalysis data, the faster warming
in the lower and middle troposphere over the continent in the recent decade is
suggested to be important for the out-of-phase decadal HD variation in YRD. The
thermal anomaly not only reverses the zonal thermal difference of land-sea to
stimulate the anomalous southerlies over YRD leading to reduced prevailing north
wind in winter, but also develops the deep inversion below the mid-troposphere to
enhance the atmospheric stability. As a result, more frequent and persistent air
stagnations in recent decade are expected for the reduction of atmospheric
horizontal dispersion and vertical diffusion capacity leading to more occurrence
of wintertime HD in YRD.
PMID- 28501017
TI - Golgi-independent routes support protein disulfide isomerase externalization in
vascular smooth muscle cells.
AB - Extracellular pools of intracellular molecular chaperones are increasingly
evident. The peri/epicellular(pec) pool of the endoplasmic reticulum redox
chaperone protein disulfide isomerase-A1(PDI) is involved in thrombosis and
vascular remodeling, while PDI externalization routes remain elusive. In
endothelial cells, vesicular-type PDI secretion involves classical and
unconventional pathways, while in platelets PDI exocytosis involves actin
cytoskeleton. However, little is known about pecPDI in vascular smooth muscle
cells(VSMC). Here, we showed that VSMC display a robust cell-surface(cs) PDI
pool, which binds to cs independently of electrostatic forces. However,
contrarily to other cells, soluble secreted PDI pool was undetectable in VSMC.
Calcium ionophore A23187 and TNFalpha enhanced VSMC csPDI. Furthermore, VSMC PDI
externalization occurred via Golgi-bypass unconventional route, which was
independent of cytoskeleton or lysosomes. Secreted PDI was absent in ex vivo wild
type mice aortas but markedly enhanced in PDI-overexpressing mice. Such
characterization of VSMC pecPDI reinforces cell-type and context specific routes
of PDI externalization.
PMID- 28501018
TI - Geographic mobility and potential bridging for sexually transmitted infections in
Agbogbloshie, Ghana.
AB - Short-term mobility can significantly influence the spread of infectious disease.
In order for mobile individuals to geographically spread sexually transmitted
infections (STIs), individuals must engage in sexual acts with different partners
in two places within a short time. In this study, we considered the potential of
mobile individuals as bridge populations - individuals who link otherwise
disconnected sexual networks and contributed to ongoing STI transmission. Using
monthly retrospective panel data, we examined associations between short-term
mobility and sexual partner concurrency in Agbogbloshie, Ghana. We also examined
bridging by the location of sex acts and the location of sexual partners in
concurrent triads, and whether mobile individuals from our sample were more
likely to be members of geographic bridging triads. Although reported rates of
sexual partnership concurrency were much higher for men compared to women,
mobility was only associated with increased concurrency for women. Additionally,
this association held for middle-distance mobility and short-duration trips for
women. Taking into account the location of sex acts and the location of sexual
partners, about 22% of men (21.7% and 22.4% for mobile and non-mobile men,
respectively) and only 3% of women (1.4% and 3.3% for mobile and non-mobile
women, respectively) were potential bridges for STIs over the last year. Our
results highlight the gendered nature of mobility and sexual risk behavior,
reflecting the normative social context that encourages women to conceal certain
types of sexual behavior.
PMID- 28501019
TI - Towards a feminist understanding of intersecting violence against women and
children in the family.
AB - While intimate partner violence (IPV) against women and violence against children
(VAC) have emerged as distinct fields of research and programming, a growing
number of studies demonstrate the extent to which these forms of violence overlap
in the same households. However, existing knowledge of how and why such co
occurrence takes place is limited, particularly in the Global South. The current
study aims to advance empirical and conceptual understanding of intersecting IPV
and VAC within families in order to inform potential programming. We explore
shared perceptions and experiences of IPV and VAC using qualitative data
collected in December 2015 from adults and children in Kampala, Uganda (n = 106).
We find that the patriarchal family structure creates an environment that
normalizes many forms of violence, simultaneously infantilizing women and
reinforcing their subordination (alongside children). Based on participant
experiences, we identify four potential patterns that suggest how IPV and VAC not
only co-occur, but more profoundly intersect within the family, triggering cycles
of emotional and physical abuse: bystander trauma, negative role modeling,
protection and further victimization, and displaced aggression. The discussion is
situated within a feminist analysis, including careful consideration of maternal
violence and an emphasis on the ways in which gender and power dynamics can
coalesce and contribute to intra-family violence.
PMID- 28501021
TI - The application of a feedback-informed approach in psychological service with
youth: Systematic review and meta-analysis.
AB - Research with adults has consistently demonstrated that the use of regular client
feedback in psychological services can improve outcomes. However, there appear to
be fewer studies with youth. The purpose of the current review was to
explore/assess (1) current developments in research on the use of feedback
informed approaches in mental health interventions or services for youth 10
19years of age; (2) the efficacy of client feedback in youth treatment settings;
and (3) consider future directions for research. A total of 12 studies were
included in this review, comprising a meta-analysis (n=9) and a qualitative
review (n=3). Most studies assessed the benefits of a feedback framework in terms
of symptom severity, functioning levels and/or goal attainments in therapy (i.e.,
ratings on the feedback-informed tools). The Hedges's g indexes of 0.20 (for
independent-groups trials), 0.32 (single-group trials) and 0.28 (for all trials)
suggest that the collection and application of continuous feedback from youth
clients throughout the course of the interventions/services can boost and produce
beneficial outcomes for the youth, while noting the feedback effect to be in the
small range. Based on these initial findings, implications for future research
and clinical practice are discussed, including considering fruitful research
directions.
PMID- 28501020
TI - Educational gains in cause-specific mortality: Accounting for cognitive ability
and family-level confounders using propensity score weighting.
AB - A negative educational gradient has been found for many causes of death. This
association may be partly explained by confounding factors that affect both
educational attainment and mortality. We correct the cause-specific educational
gradient for observed individual background and unobserved family factors using
an innovative method based on months lost due to a specific cause of death re
weighted by the probability of attaining a higher educational level. We use data
on men with brothers from the Swedish Military Conscription Registry (1951-1983),
linked to administrative registers. This dataset of some 700,000 men allows us to
distinguish between five education levels and many causes of death. The empirical
results reveal that raising the educational level from primary to tertiary would
result in an additional 20 months of survival between ages 18 and 63. This
improvement in mortality is mainly attributable to fewer deaths from external
causes. The highly educated gain more than nine months due to the reduction in
deaths from external causes, but gain only two months due to the reduction in
cancer mortality and four months due to the reduction in cardiovascular
mortality. Ignoring confounding would lead to an underestimation of the gains by
educational attainment, especially for the less educated. Our results imply that
if the education distribution of 50,000 Swedish men from the 1951 cohort were
replaced with that of the corresponding 1983 cohort, 22% of the person-years that
were lost to death between ages 18 and 63 would have been saved for this cohort.
PMID- 28501022
TI - Sociodemographic profile of an Olympic team.
AB - OBJECTIVES: To document the distribution of sociodemographic markers (race and
relative access to wealth) in athletes participating at the summer and Winter
Olympic Games (OGs). STUDY DESIGN: Cross-sectional descriptive epidemiological
study. METHODS: Sociodemographic data were collected from publically available
resources for all athletes representing four countries (Canada, United States of
America, Great Britain and Australia) at the 2014 Sochi Winter OGs and 2016 Rio
Summer OGs. The prevalence of white and privately educated athletes were
identified for each sport, country, and team with consideration and comparison to
the general population. Access indices (i.e. the combined race socio-economic
access index [CAI]) were developed to describe the relative distribution of white
and privately educated athletes representing each sport, country and team
compared to the respective general population. RESULTS: A total of 568 winter and
1643 summer athletes were included in this study. Privately educated athletes
constituted 30.3% and 32.7% of winter and summer athletes, respectively; while
94.9% of winter and 81.7% of summer athletes were white. The CAIs of the
Canadian, American, British and Australian winter Olympic teams were 0.52, 0.42,
0.61 and 0.45, respectively. The CAIs, for the Canadian, American, British and
Australian summer Olympic teams were 0.89, 1.13, 0.82 and 0.83, respectively.
Summer and winter sports with the greatest and least racial and socio-economic
biases were identified. CONCLUSION: Racial and socio-economic biases were
identified in both summer and winter Olympic sports; predominantly favouring
white and privately educated Olympic athletes. These findings prompt further
inquiry into barriers for sport-specific participation and advancement, in
addition to the practice of providing substantial public resources in support for
Olympic sports and athletes.
PMID- 28501023
TI - Force-velocity relationship of leg muscles assessed with motorized treadmill
tests: Two-velocity method.
AB - Linear regression models applied on force (F) and velocity (V) data obtained from
loaded multi-joint functional movement tasks have often been used to assess
mechanical capacities of the tested muscles. The present study aimed to explore
the properties of the F-V relationship of leg muscles exerting the maximum
pulling F at a wide range of V on a standard motorized treadmill. Young and
physically active male and female subjects (N=13+15) were tested on their maximum
pulling F exerted horizontally while walking or running on a treadmill set to 8
different velocities (1.4-3.3m/s). Both the individual (median R=0.935) and
averaged across the subjects F-V relationships (R=0.994) proved to be
approximately linear and exceptionally strong, while their parameters depicting
the leg muscle capacities for producing maximum F, V, and power (P; proportional
to the product of F and V) were highly reliable (0.84 Portuguese) and backward (Portuguese -> English) translation,
by independent native speaker translators. After review, a preliminary version
was created to be pilot tested among Portuguese patients. As a Brazilian version
was already available for Quality of Life Questionnaire - OES18 (esophageal
module), the questionnaire was simply culturally adapted and pilot tested. Both
cancer and non-cancer patients were included. RESULTS: Overall, 30 patients
completed the Portuguese version of each questionnaire. Afterwards, a structured
interview was conducted to find and report any problematic items. Troublesome
items and wording were changed according to the pilot testing results. The final
versions were sent to the European Organisation for Research and Treatment of
Cancer Quality of Life Group and approved. CONCLUSION: The Portuguese versions of
the European Organization for Research and Treatment of Cancer Quality of Life
Questionnaire - OES18 (esophageal module) and OG25 (esophagogastric module)
questionnaires are useful, reliable and valid tools for measuring health-related
quality of life in patients with esophageal and esophagogastric cancers,
respectively. They can now be used in clinical setting and for scientific
purposes.
PMID- 28501039
TI - Symptomatic Control in End-of-Life Patients.
AB - End-of-life patients present a variety of symptoms that cause suffering for them
and their respective families. Health professionals throughout their university,
internship and medical careers are ill-prepared to manage and improve the quality
of life of these patients. This article aims to provide basic skills in the
symptomatic management of end-of-life patients, focusing in particular on the
control of pain, dyspnoea, fatigue, nausea, vomiting and anorexia. It also aims
to draw attention to basic concepts of control concerning refractory symptoms and
palliative sedation.
PMID- 28501038
TI - [Superiority of 18F-FNa PET/CT for Detecting Bone Metastases in Comparison with
Other Diagnostic Imaging Modalities].
AB - INTRODUCTION: The 18F-NaF positron emission tomography/computed tomography is
being considered as an excellent imaging modality for bone metastases detection.
This ability was compared with other imaging techniques. MATERIAL AND METHODS: We
retrospectively evaluated 114 patients who underwent 18F-NaF positron emission
tomography/ computed tomography. Of these, 49 patients also had bone
scintigraphy, 61 18F-FDG positron emission tomography/computed tomography and 10
18F-FCH positron emission tomography/computed tomography. We identified the
technique that detected the largest number of bone metastases. For the detection
of skeletal metastases with the 18F-NaF positron emission tomography/computed
tomography study, the contribution of the positron emission tomography component
was compared with the contribution of the computed tomography component. Cases in
which 18F-NaF positron emission tomography/computed tomography and bone
scintigraphy required further additional tests for diagnosis clarification were
registered. RESULTS: The 18F-NaF positron emission tomography/computed tomography
was superior to bone scintigraphy in 49% of the patients (p < 0.001); it was
superior to 18F-FDG positron emission tomography/computed tomography in 59% of
the patients (p < 0.001) and it was superior to 18F-FCH positron emission
tomography/computed tomography in 40% of the patients (p < 0.001). None of the
compared imaging techniques were superior to 18F-NaF positron emission
tomography/computed tomography. The positron emission tomography component was
superior to computed tomography in 35% of the cases (p < 0.001). Further
investigation was suggested in only 3.5% of patients who underwent 18F-NaF
positron emission tomography/computed tomography (45% for bone scintigraphy) (p <
0.001). DISCUSSION: As with other authors, our experience also confirms that 18F
NaF positron emission tomography/computed tomography is an excellent imaging
modality for the detection of bone metastases, detecting lesions in more patients
and more lesions per patient. CONCLUSION: The 18F-NaF positron emission
tomography/computed tomography showed a superior ability for the detection of
bone metastases when compared with bone scintigraphy, 18F-FDG positron emission
tomography/computed tomography and 18F-FCH positron emission tomography/computed
tomography.
PMID- 28501040
TI - [The Relationship Between Immunodepression and the Development of Skin Cancer].
AB - The effects of immunodepression on several disease states have constituted an
important area of research, leading to the identification of relevant
associations between immunodepression and a vast set of comorbidities, including
infectious diseases, cardiovascular diseases and cancer. Research on the effects
of immunodepression has mostly been conducted in individuals under
immunodepression by the human immunodeficiency virus and transplant recipients
under pharmacological immunosuppression, due to the difficulties in obtaining
relevant samples sizes in other contexts of immunodepression. Overall,
immunosuppressed individuals tend to show increased incidence of malignancies,
but only transplant recipients show significantly increased incidence of skin
cancer; human immunodeficiency virus-infected individuals only show increased
incidence of malignancies of infectious origin. This paper presents a literature
review on the effects of immunodepression in the development of tumours in
humans, with special emphasis on the development of the different types of skin
cancer.
PMID- 28501041
TI - Trauma Patient with Fat Embolism Detected on Computed Tomography.
AB - Fat embolism is frequent following fractures of long bones, however the
development of the clinical syndrome of fat embolism (characterized by
progressive respiratory distress, mental status depression and petechial rash) is
rare, but relevant because of its potential severity. We report a case of a
trauma patient with multiple fractures of the right lower limb in whom an
emergency computed tomography scan showed fat emboli within the lumen of the
homolateral common femoral vein. The imaging detection of macroscopic fat emboli
should alert the clinician to the potential for subsequent fat embolism syndrome.
PMID- 28501042
TI - Behavior Changes and Gait Unsteadiness: The Value of Imaging and Prompt
Neurosurgical Intervention.
AB - Cavernous angiomas are central nervous system malformations. Most common
manifestations are seizures and acute focal neurological deficits. We present a
case report of a seventy-one year-old man with a two-month history of behavior
changes, attention deficit and indifference followed by gait unsteadiness.
Neuropsychological evaluation showed severe cognitive impairment and executive
dysfunction. Head computed tomography depicted a supraventricular hydrocephaly.
Magnetic resonance imaging revealed a small hemorrhage, contiguous to a
mesencephalic cavernous angioma, obstructing the Sylvius aqueduct, causing
secondary hydrocephalus. Four months after endoscopic ventriculocisternostomy,
neuropsychological evaluation showed improvement and the patient regained
autonomy. Parenchyma cavernous angiomas causing direct hemorrhage and subsequent
obstruction of the Sylvian aqueduct are uncommon. Sub-acute behavior and mental
state abnormalities are rare first manifestations of cavernous angioma and
requires high clinical suspicion for its correct diagnosis. Magnetic resonance
imaging evaluation is crucial in the detection of such patients as prompt
neurosurgical intervention may substantially improve cognitive function.
PMID- 28501043
TI - Aortic Dissection Mimicking ST Elevation Myocardial Infarction.
PMID- 28501044
TI - Scrotal Cystocele by Computed Tomography and Ultrasound.
PMID- 28501045
TI - [Letter to the Editor: Comments to Training and Medical Education].
PMID- 28501046
TI - Reporting pre-exposure prophylaxis use in Craigslist personal advertisements
among men seeking sex with men in the United States.
AB - This study describes the self-reported use of pre-exposure prophylaxis (PrEP) in
the personal advertisements of men seeking sex with men in the United States on
the online classified advertisement site, Craigslist. Overall self-reported PrEP
use was low (0.20%; 95% confidence interval (CI)=0.18-0.22). However, PrEP use in
personal ads was described in conjunction with seeking sexual risk behaviours
including 'bareback' sex (22.7%; 95% CI=17.7-27.7%) and sex with substance use
(26.8%; 95% CI=21.5-32.1%). Only 4.0% of personal ads sought safe sex (3.3%; 95%
CI=1.2-5.4%) or required condoms (0.7%; 95% CI=-0.3-1.7%). Our findings
underscore the need for increased public PrEP awareness, particularly among men
seeking sex with men, as well as the importance of healthcare providers
emphasising sexually transmissible infection prevention behaviours (i.e. condom
use) used in conjunction with PrEP.
PMID- 28501047
TI - Realising the potential of health needs assessments.
AB - Population-level assessment and planning has traditionally been the role of
public health departments but in establishing Primary Health Networks (PHNs), the
Australian Government has instituted a new mechanism for identifying community
needs and commissioning services to meet those needs. If PHNs are to achieve the
vision of nimble organisations capable of identifying and addressing local health
needs via integrated health and social services, several things need to occur.
First, PHN funding schedules must become more flexible. Second, the Federal
health department must maintain an open dialogue with PHNs, permit waivers in
funding schedules to suit local conditions and be prepared to back innovations
with seed investment. Third, health data exchange and linkage must be accelerated
to better inform community needs assessments and commissioning. Finally, PHNs
must be encouraged and supported to develop collaborations both within and
outside the health sector in order to identify and address a broad set of health
issues and determinants. By following these principles, PHNs may become leading
change agents in the Australian healthcare system.
PMID- 28501049
TI - Distrusting doctors.
AB - Objective The aim of the present study was to describe how policy makers
(bureaucrats and politicians) in Australia and Ontario (Canada) perceive evidence
provided by doctors to substantiate applications for disability income support
(DIS) by their patients with mental illnesses. Because many mental illnesses
(e.g. depression) lack diagnostic tests, their existence and effects are more
difficult to demonstrate than most somatic illnesses.Methods Semi-structured
interviews were conducted with 45 informants, all influential in the design of
the assessment of DIS programs. The informants were subcategorised into
advocates, legal representatives, doctors (general practitioners (GPs) and
specialists (e.g. psychiatrists)), policy insiders and researchers. Informants
were found through snowball sampling. Following the principles of grounded
theory, data collection and analysis occurred in tandem.Results Informants
expressed some scepticism about doctors' evidence. Informants perceived that
doctors could, due to lack of diagnostic certainty, 'write these things
[evidence] however [they] want to'. Psychiatrists, perceived as having more time
and skills, were considered as providing more trustworthy evidence than
GPs.Conclusion Doctors, providing evidence to support applications, play an
important role in determining disability. However, policy makers perceive
doctors' evidence about mental illnesses as less trustworthy than evidence about
somatic illnesses. This affects decisions by government adjudicators.What is
known about the topic? Doctors (GPs and psychiatrists) are often asked to provide
evidence to substantiate a DIS application for those with mental illnesses. We
know little about the perception of this evidence by the policy makers who
consider these applications.What does this paper add? Policy makers distrust
doctors' evidence in relation to mental illnesses. This is partly because many
mental illnesses lack diagnostic proof, in contrast with evidence for somatic
conditions, where the disability is often visible and proven through diagnostic
tests. Furthermore, GPs' evidence is considered less trustworthy than that of
psychiatrists.What are the implications for practitioners? Although doctors'
evidence is often required, the utility of their evidence is limited by policy
makers' perceptions.
PMID- 28501048
TI - Systematic review of evidence underpinning non-pharmacological therapies in
dementia.
AB - Objective Dementia is one of the most common illnesses worldwide, and is one of
the most important causes of disability in older people. Currently, dementia
affects over 35million people around the globe. It is expected that this number
will increase to 65.7million by 2030. Early detection, diagnosis and treatment to
control the principal behaviour symptoms may help reduce these numbers and delay
the progression to more advanced and dangerous stages of this disorder with
resultant increase quality of life for those affected. The main goal of the
present systematic literature review was to examine contemporary evidence
relating to non-pharmacological therapy in the treatment of dementia.Methods To
achieve the study goal, the Preferred Reporting Items for Systematic Reviews and
Meta-Analyses (PRISMA) statement was used.Results This study identified the five
most common behaviours in patients with dementia as aggression, wandering,
agitation, apathy and sleep disturbances. Two non-pharmacological therapies were
the most studied treatment: music therapy and aromatherapy. Ten other non
pharmacological therapies were also identified, but these lack a sufficient
evidence-base.Conclusion Although all the therapies identified could be used as
part of the treatment of behavioural symptoms, there is insufficient evidence
relating to the indications, appropriate use and effectiveness of these therapies
to apply in each behavioural treatment. Thus, the present study has demonstrated
a significant research gap.What is known about the topic? Despite the widespread
use of many different types of therapies, there is limited evidence regarding the
efficacy of non-pharmaceutical therapies deployed in the management of behaviours
of concern manifested by some people who suffer with dementia in all its
forms.What does this paper add? This systematic review examines contemporary
evidence from the literature to determine whether there is an evidence base
available that would underpin the use of these therapies. This report on a PRISMA
systematic review of the available literature demonstrates that only two
therapies have some evidence to underpin the use of these non-pharmaceutical
therapies and that a significant research gap is exists.What are the implications
for practitioners? The implications for practitioners is that significant
research effort is required to determine the efficacy of many of the therapies
that are currently deployed, and thus many of the therapies used lack an evidence
base at this time.
PMID- 28501050
TI - Do patients discharged from advanced practice physiotherapy-led clinics re
present to specialist medical services?
AB - Objective The aim of the present study was to determine the rates of re-referral
to specialist out-patient clinics for patients previously managed and discharged
from an advanced practice physiotherapy-led service in three metropolitan
hospitals. Methods A retrospective audit was undertaken of 462 patient cases with
non-urgent musculoskeletal conditions discharged between 1 April 2014 and 30
March 2015 from three metropolitan hospitals. These patients had been discharged
from the physiotherapy-led service without requiring specialist medical review.
Rates and patterns of re-referral to specialist orthopaedic, neurosurgical,
chronic pain, or rheumatology services within 12 months of discharge were
investigated. Results Forty-six of the 462 patients (10.0%) who were managed by
the physiotherapy-led service were re-referred to specialist medical orthopaedic,
neurosurgical, chronic pain or rheumatology departments within 12 months of
discharge. Only 22 of these patients (4.8%) were re-referred for the same
condition as managed previously and discharged. Conclusions Ninety-five per cent
of patients with non-urgent musculoskeletal conditions managed by an advanced
practice physiotherapy-led service at three metropolitan hospitals did not re
present to access public specialist medical services for the same condition
within 12 months of discharge. This is the first time that re-presentation rates
have been reported for patients managed in advanced practice physiotherapy
services and the findings support the effectiveness of these models of care in
managing demand for speciality out-patient services. What is known about the
topic? Advanced practice physiotherapy-led services have been implemented to
address the needs of patients referred with non-urgent musculoskeletal conditions
to hospital specialist out-patient services. Although this model is widely used
in Australia, there has been very little information about whether patients
managed in these services subsequently re-present for further specialist medical
care. What does this paper add? This paper identifies that the majority (95%) of
patients managed by an advanced practice physiotherapy-led service did not re
present for further medical care for the same condition within 12 months of
discharge. What are the implications for practitioners? This paper supports the
use of advanced practice physiotherapy-led services in the management of
overburdened neurosurgical and orthopaedic specialist out-patient waiting lists.
PMID- 28501051
TI - 2018: the end of a cycle in Radiologia.
PMID- 28501052
TI - Self-ligating Brackets May Not Have Clinical Advantages Over Conventional
Brackets for the Periodontal Health of Adolescent Orthodontic Patients.
AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: The effect of bracket ligation on
the periodontal status of adolescents undergoing orthodontic treatment. A
systematic review and meta-analysis. Arnold S, Koletsi D, Patcas R, Eliades T. J
Dent 2016; 54:13-24. SOURCE OF FUNDING: The authors did not report any funding
source information for the study TYPE OF STUDY/DESIGN: Systematic review with
meta-analysis of data.
PMID- 28501053
TI - The Risk of Medication-Related Osteonecrosis of the Jaw After Dental Extraction
is Higher for Patients on Intravenous as Compared With Oral Antiresorptive Drugs.
AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Occurrence and risk indicators of
medication-related osteonecrosis of the jaw after dental extraction: a systematic
review and meta-analysis. Gaudin E, Seidel L, Bacevic M, Rompen E, Lambert F. J
Clin Periodontol 2015;42(10):922-32. SOURCE OF FUNDING: Internal institutional
support TYPE OF STUDY/DESIGN: Systematic review with meta-analysis of data.
PMID- 28501054
TI - Cement- and Screw-Retained Implant-Supported Restorations Showed Comparable
Marginal Bone Loss and Implant Survival Rate.
AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Evaluation of cement-retained versus
screw-retained implant-supported restorations for marginal bone loss: A
systematic review and meta-analysis. Lemos CAA, de Souza Batista VE, de Faria
Almeida DA, Junior JFS, Verri FR, Pellizzer EP. J Prosthet Dent 2016; 115(4):419
27. SOURCE OF FUNDING: Sao Paulo Research Foundation (FAPESP), grant 2014/02490
8. TYPE OF STUDY/DESIGN: Systematic review with meta-analysis of data.
PMID- 28501055
TI - Limited Evidence Suggests There Is No Difference Between the Clinical Longevity
of direct vs Indirect Composite Resins in Class I and II Cavities.
AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Longevity of direct and indirect
resin composite restorations in permanent posterior teeth: A systematic review
and meta-analysis. Da Veiga AMA, Cunha AC, Ferreria DMTP, Fidalgo TK, Chianca TK,
Reis KR, Maia LC. J Dent 2016;54:1-12. SOURCE OF FUNDING: Federal University of
Rio de Janeiro, Brazil. This study was conducted as part of the master degree for
one of the authors under supervision by another author. TYPE OF STUDY/DESIGN:
Systematic review with meta-analysis.
PMID- 28501056
TI - Resin Infiltration May Be Considered as a Color-Masking Treatment Option for
Enamel Development Defects and White Spot Lesions.
AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Is resin infiltration an effective
esthetic treatment for enamel development defects and white spot lesions? A
systematic review. Borges AB, Caneppele TMF, Masterson D, Maia LC. J Dent
2017;56:11-8. SOURCE OF FUNDING: Information not available. TYPE OF STUDY/DESIGN:
Systematic review.
PMID- 28501057
TI - Mini Implant-Retained Complete Overdenture Can be an Alternative Treatment Option
for Selected Patients.
AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Complete overdentures retained by
mini implants: A systematic review. Lemos CAA, Verri FR, de Souza Batista VE,
Santiago JF Jr, Mello CC, Pellizzer EP. J Dent 2017;57:4-13. SOURCE OF FUNDING:
The authors did not report any external sources of fund. TYPE OF STUDY/DESIGN:
Systematic review.
PMID- 28501058
TI - Limited-Quality Evidence Suggests That Early Caries Experience at Age 6 years May
Predict Low Oral Health-Related Quality of Life at Age 10 years.
AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Early Caries Predicts Low Oral
Health-Related Quality of Life at a Later Age. Kragt L, van der Tas JT, Moll HA,
Elfrink ME, Jaddoe VW, Wolvius EB, Ongkosuwito EM. Caries Res. 2016; 50(5):471-9.
SOURCE OF FUNDING: This study was funded by (1) the Erasmus Medical Center,
Rotterdam, the Erasmus University, Rotterdam, (2) the Netherlands Organization
for Health Research and Development, (3) an unrestricted grant from GABA,
Therwil, Switzerland, (4) the Netherlands Organization for Health Research and
Development (VIDI 016.136.361), and a (5) consolidator grant from the European
Research Council (ERC-2014- CoG-64916). TYPE OF STUDY/DESIGN: Prospective Cohort
Study.
PMID- 28501059
TI - Stopping Anticoagulation Therapy Before Implant and Bone Grafting Surgery May Not
Be Necessary to Prevent Bleeding Events.
AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Management of anticoagulated
patients in implant therapy: a clinical comparative study. Clemm R, Neukam FW,
Rusche B, Bauersachs A, Musazada S, Schmitt CM. Clin Oral Implants Res
2016;27(10):1274-82. SOURCE OF FUNDING: Information not available TYPE OF
STUDY/DESIGN: Cohort study.
PMID- 28501060
TI - Analysis of Orange/Red Fluorescence for Bacterial Activity in Initial Carious
Lesions May Provide Accurate Lesion Activity Assessment for Caries Progression.
AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Orange/Red Fluorescence of Active
Caries by Retrospective Quantitative Light-Induced Fluorescence Image Analysis.
Gomez GF, Eckert GJ, Zandona AF.Caries Res 2016; 50(3):295-302. SOURCE OF
FUNDING: The study was partially supported by a grant from NIH/NIDCR
(R01DE017890) TYPE OF STUDY/DESIGN: Retrospective case-control design using the
data collected in a longitudinal study.
PMID- 28501061
TI - Limited Evidence Shows That a Motivational Interviewing Approach May be the Most
Effective Behavioral Intervention for Reducing Dental Caries in Children.
AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Preventing childhood caries: a
review of recent behavioral research. Albino J, Tiwari T. J Dent Res
2016;95(1):35-42. SOURCE OF FUNDING: Government. NIDCR grants U54DE019259 and
1K99DE024758-01A1. TYPE OF STUDY/DESIGN: Literature review.
PMID- 28501062
TI - Systemic Propolis (Adjuvant to Nonsurgical Periodontal Treatment) May aid in
Glycemic Control and Periodontal Health in Type 2 Diabetes of Long Duration.
AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Propolis improves periodontal status
and glycemic control in patients with type 2 DM and chronic periodontitis: A
randomized clinical trial. El-Sharkawy HM, Anees MM, Van Dyke TE. J Periodontol
2016;87:1418-1426. SOURCE OF FUNDING: Information not available. TYPE OF
STUDY/DESIGN: Randomized controlled trial (RCT).
PMID- 28501063
TI - Case Selection is Critical for Successful Outcomes Following Immediate Implant
Placement in the Esthetic Zone.
AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Immediate versus delayed implant
placement after anterior single tooth extraction: the timing randomized
controlled clinical trial. Tonetti MS, Cortellini P, Graziani F, Cairo F, Lang
NP, Abundo R, Conforti GP, Marquardt S, Rasperini G, Silvestri M, Wallkamm B,
Wetzel A. Journal of Clinical Periodontology 2017;44(2):215-24. SOURCE OF
FUNDING: Nonprofit, Foundations: European Research Group on Periodontology,
Genova, Italy Industry: Thommen Medical AG, Switzerland and Geistlich AG,
Switzerland (biomaterials). TYPE OF STUDY/DESIGN: Randomized controlled trial.
PMID- 28501064
TI - Four or More Amalgam Fillings Correlate With Higher Blood Mercury Levels in
Pregnant Women but Not High Enough to be of Health Concern.
AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Dental associations with blood
mercury in pregnant women. Golding J, Steer CD, Gregory S, Lowery T, Hibbeln JR,
Taylor CM. Community Dent Oral Epidemiol 2016; 44: 216-22. SOURCE OF FUNDING:
This study was funded by a combination of government (UK Medical Research
Council), foundation/nonprofit (the Welcome Trust) and university (University of
Bristol, UK) grants. TYPE OF STUDY/DESIGN: Cross-sectional.
PMID- 28501065
TI - Limited and Nongeneralizable Evidence Shows Neighborhood Contextual Factors May
Be Linked to Dental Treatment but Not Untreated Caries Prevalence.
AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Neighbourhood Determinants of Caries
Experience in Preschool Children: A Multilevel Study. Priesnitz MC, Celeste RK,
Pereira MJ, Pires CA, Feldens CA, Kramer PF. Caries Res 2016;50(5):455-61. SOURCE
OF FUNDING: None. TYPE OF STUDY/DESIGN: Cross-sectional study.
PMID- 28501066
TI - Taxing Sugary Beverages Reduces Their Purchase, Especially Among Poor Households.
AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Beverage purchases from stores in
Mexico under the excise tax on sugar sweetened beverages: observational study.
Colchera MA, Popkin BM, Rivera JA, Ng SW. Br Med J 2016;352:h6704. SOURCE OF
FUNDING: Bloomberg Philanthropies, Robert Wood Johnson Foundation, Instituto
Nacional de Salud Publica and Carolina Population Center. TYPE OF STUDY/DESIGN:
Observational study.
PMID- 28501067
TI - In Defense of Flossing: Can We Agree It's Premature to Claim Flossing is
Ineffective to Prevent Dental Caries?
AB - Current evidence pertaining to the effectiveness of flossing and caries
prevention is potentially being misinterpreted by health oversight bodies, which
may have significant implications for current and future public flossing
guidelines. We identify and discuss several methodological deficiencies,
including the lack of validated measures of flossing skill, over-reliance on self
reported flossing behavior, and the lack of current guidelines on how to
interpret and apply evidence-based findings to specific clinical scenarios that
are present in the studies of flossing effectiveness included in the Cochrane
Review. As such, we argue that it is premature for health oversight bodies to
conclude that flossing is ineffective in the prevention of dental caries. Our
research group, which is funded by the National Institutes of Health (NIH), is
developing a valid and reliable provider-observed measure of tooth brushing and
flossing skill that may help promote higher quality flossing evidence in the
future.
PMID- 28501068
TI - Preliminary Evidence for the Complete Digital Esthetic Rehabilitation Treatment:
Case Report and 1-Year Follow-up.
AB - PURPOSE: To show through computer-aided design and manufacturing technology
combined with novel digital acquisition images and the right restorative material
that the technology can provide an easier and predictable workflow for general
practitioners. BASIC PROCEDURE: This case report presents a fully digital
treatment of a 59-year-old patient with tooth-supported crowns and provides a
detailed step-by-step digital technique to obtain a successful result.
CONCLUSION: By avoiding traditional impression and fixed prosthetic techniques,
excellent clinical results can be obtained, minimizing the required steps and
simplifying the overall procedure. This adds information to the current
literature, allowing general practitioners to choose the best treatment option.
The function and esthetics remained unaltered over a 1-year follow-up period. No
fracture or decementation was observed.
PMID- 28501069
TI - Emergency Department Utilization related to dental conditions and distribution of
Dentists, Nebraska 2011-2013.
AB - PURPOSE: This study aims to provide estimates of hospital-based emergency
department (ED) visits due to dental conditions in Nebraska and to examine
patient-related characteristics associated with ED charges. In addition, this
study provides dental-related ED visits and distribution of dentists by county.
METHODS: For the study, we used the State Emergency Department Database for
Nebraska for the years 2011 through 2013 and the Health Resources and Services
Administration's Area Health Resource File. All ED visits with dental conditions
in Nebraska were selected. The primary outcome variable was hospital-based ED
charges. Multivariable linear regression model was used to examine the effects of
patient-related factors on ED charges. RESULTS: During the study period, a total
of 9943 dental-related ED visits occurred. Of these, 55.5% patients aged between
25 and 44 years. Thirty-nine percent of all dental ED visits had patients who
were self-financed or uninsured. Twenty counties in Nebraska do not have a
dentist, and nine counties had more than 50 ED visits per 10,000 population.
Patients residing in urban areas paid significantly higher charges than those
living in rural towns, small rural towns, or isolated rural areas. The mean and
total ED charges attributed to dental conditions for the entire study period were
$934 and $9.3 million, respectively. CONCLUSION: Patients who are uninsured, aged
25-44 years, covered by private insurance, and residing in urban areas are
identified to be at high risk. There is a need to develop health policies and
programs to improve access to dental care in rural states.
PMID- 28501070
TI - Use of Evidence-Based Decision-Making in Comprehensive Dental Treatment of a
Patient with Meth Mouth-A Case Report.
AB - OBJECTIVE: This case report illustrates the use of evidence-based practice in
formulating a comprehensive dental treatment plan for a patient who presented
himself with signs of oral health debilitation accompanying methamphetamine (MA)
abuse called "meth mouth" with the goal of providing dental care practitioners in
Saudi Arabia with an insight into the global problem of MA abuse and its impact
on oral health. BACKGROUND: This report documents the case of a 22-year-old male
patient who reported to the clinic with rampant caries caused due to MA abuse
exacerbated by poor oral hygiene and smoking habit. METHOD: The treatment plan of
this present case was formulated on the lines of the evidence-based dentistry
approach. A clinical question was composed based on the Problem, Intervention,
Comparison, and Outcome format to identify past studies and case reports on meth
mouth. A standard search was conducted on PubMed Central. Standard guidelines on
the treatment of meth mouth were extracted from the Web site of the American
Dental Association. RESULTS: A total of 2 systematic reviews, 7 review articles,
4 epidemiologic studies, 5 case reports, and 1 American Dental Association
guideline were found. CONCLUSION: Accelerated dental decay leading to rampant
caries in young and middle-aged adults is a characteristic oral finding in MA
abusers. The most important factor that affects the prognosis of dental care is
complete cessation of MA use by the patient.
PMID- 28501072
TI - Letter to the Editor.
PMID- 28501071
TI - In Patients With Symptomatic Irreversible Pulpitis, Articaine is 3.6 Times More
Efficacious Than Lidocaine in Achieving Anesthetic Success When Used for
Supplementary Infiltration After Mandibular Block Anesthesia.
AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Does articaine provide an advantage
over lidocaine in patients with symptomatic irreversible pulpitis? A systematic
review and meta-analysis. Kung J, McDonagh M, Sedgley CM. J Endod 2015;
41(11):1784-94. SOURCE OF FUNDING: The study was supported by the OHSU Department
of Endodontology Les Morgan Endowment Fund and a resident research grant from the
American Association of Endodontists Foundation TYPE OF STUDY/DESIGN: Systematic
review with meta-analysis of data.
PMID- 28501073
TI - Prophylactic Hemodialysis for Protection Against Gadolinium-Induced Nephrogenic
Systemic Fibrosis: A Doll's House.
PMID- 28501074
TI - Scared to the Marrow: Pitfalls and Pearls in Renal Imaging.
PMID- 28501075
TI - Gadolinium Retention and Toxicity-An Update.
AB - Until 2006, the main considerations regarding safety for all gadolinium-based
contrast agents (GBCAs) were related to short-term adverse reactions. However,
the administration of certain "high-risk" GBCAs to patients with renal failure
resulted in multiple reported cases of nephrogenic systemic fibrosis. Findings
have been reported regarding gadolinium deposition within the body and various
reports of patients who report suffering from acute and chronic symptoms
secondary to GBCA's exposure. At the present state of knowledge, it has been
proved that gadolinium deposits also occur in the brain, irrespective of renal
function and GBCAs stability class. To date, no definitive clinical findings are
associated with gadolinium deposition in brain tissue. Gadolinium deposition
disease is a newly described and probably infrequent entity. Patients presenting
with gadolinium deposition disease may show signs and symptoms that somewhat
follows a pattern similar but not identical, and also less severe, to those
observed in nephrogenic systemic fibrosis. In this review, we will address
gadolinium toxicity focusing on these 2 recently described concerns.
PMID- 28501076
TI - Intravenous Contrast: Friend or Foe? A Review on Contrast-Induced Nephropathy.
AB - Intravenous iodinated contrast is used in many contrasted imaging studies ranging
from computed tomography to angiography. The risks of contrast-induced
nephropathy (CIN) and its incidence have not been clearly defined. Most iodinated
contrast media used today are hypertonic compared with serum osmolality and pose
biological risks. However, the risk of CIN in the general population may be
overestimated. Confounding risk factors may contribute to acute kidney injury
other than attributable risk of contrast exposure. In high-risk populations such
as in those with CKD, CIN risk may be higher and thus caution should be exerted
with contrast exposure. The volumes of contrast should be minimized as much as
possible and hemodynamic status should be optimized before contrast
administration.
PMID- 28501078
TI - The Role of PET Scanning in the Evaluation of Patients With Kidney Disease.
AB - Patients with underlying kidney disease are often required to undergo imaging for
a variety of purposes including diagnosis and prognosis. A test that is being
increasingly used with for this group of patients is the positron emission test
(PET) scan. In addition, combining the nuclear medicine technique (PET) with
computed tomography scan allows additional imaging advantages over either alone.
These imaging modalities are commonly used for a number of extrarenal indications
(ie, cancer, coronary artery disease, central nervous system disease, infectious
diseases, and others). They have also been used for diagnosis of acute
tubulointerstitial nephritis, evaluation and management of retroperitoneal
fibrosis, identifying infection within kidney and liver cysts, and distinguishing
complex kidney cysts from kidney cancer in patients with underlying CKD. We will
review PET scan utility in patients with kidney disease.
PMID- 28501077
TI - Recent Advances in Magnetic Resonance Imaging Assessment of Renal Fibrosis.
AB - CKD is a global public health problem. Renal fibrosis is a final common pathway
leading to progressive loss of function in CKD. The degree of renal fibrosis
predicts the prognosis of CKD. Recent studies have shown that bone marrow-derived
fibroblasts contribute significantly to the development of renal fibrosis, which
may yield novel therapeutic strategy for fibrotic kidney disease. Therefore, it
is imperative to accurately assess the degree of renal fibrosis noninvasively to
identify those patients who can benefit from antifibrotic therapy. In this
review, we summarize recent advances in the assessment of renal fibrosis by
magnetic resonance imaging.
PMID- 28501079
TI - Functional Magnetic Resonance Imaging of the Kidneys-With and Without Gadolinium
Based Contrast.
AB - Assessment of renal function with magnetic resonance imaging (MRI) has been
actively explored in the past decade. In this review, we introduce the principle
of MRI and review recent progress of MRI methods (contrast enhanced and
noncontrast) in assessing renal function. Contrast-enhanced MRI using ultra-low
dose of gadolinium-based agent has been validated for measuring single-kidney
glomerular filtration rate and renal plasma flow accurately. For routine
functional test, contrast-enhanced MRI may not replace the simple serum
creatinine method. However, for patients with renal diseases, it is often worthy
to perform MRI to accurately monitor renal function, particularly for the
diseased kidney. As contrast-enhanced MRI is already an established clinical tool
for characterizing renal structural abnormalities, including renal mass and
ureteral obstruction, it is possible to adapt the clinical MRI protocol to
measure single-kidney glomerular filtration rate and renal plasma flow, as
demonstrated by recent studies. What makes MRI unique is the promise of its
noncontrast methods. These methods include arterial spin labeling for tissue
perfusion, blood oxygen-level dependent for blood and tissue oxygenation, and
diffusion-weighted imaging for water diffusion. For each method, we reviewed
recent findings and summarized challenges.
PMID- 28501080
TI - Intravenous Contrast-Induced Nephropathy-The Rise and Fall of a Threatening Idea.
AB - Contrast-induced nephropathy (CIN) has been considered to be a cause of renal
failure for over 50 years, but careful review of past and recent studies reveals
the risks of CIN to be overestimated. Older studies frequently cited the use of
high-osmolality contrast media, which have since been replaced by low-osmolality
contrast media, which have lower risks for nephropathy. In addition, literature
regarding CIN typically describes the incidence following cardiac angiography,
whereas the risk of CIN from intravenous injection is much lower. Most of the
early published literature also lacked appropriate control groups to compare to
those that received iodinated contrast, and thus attributed rises in creatinine
to intravenous contrast without considering normal creatinine fluctuations
(frequent in patients with kidney disease) and other acute pathologic states such
as hypotension or nephrotoxic drug administration. The aim of this paper is to
review the literature detailing CIN risk, discuss why CIN risk is often
overestimated and how withholding contrast can lead to misdiagnosis and delay in
appropriate patient management.
PMID- 28501081
TI - The Impact of Excess Ligand on the Retention of Nonionic, Linear Gadolinium-Based
Contrast Agents in Patients With Various Levels of Renal Dysfunction: A Review
and Simulation Analysis.
AB - The role of gadolinium (Gd)-based contrast agents (GBCAs) in the pathophysiology
of nephrogenic systemic fibrosis (NSF) is now uncontested. Although the
definitive mechanism has not been established, the association with weaker GBCA
ligands and with reduced renal clearance supports a hypothesis that Gd release
from the GBCAs is a key process in precipitating the disease. Prevention
strategies often include the use of more stable GBCA ligands in patients with
reduced kidney function, but animal models and some clinical data suggest that
better patient outcomes can be achieved when excess ligand is administered with
weaker GBCAs; this is particularly significant for OptiMARK, which contains a
nonionic, linear ligand similar to gadodiamide, the active ingredient in
Omniscan, but contains twice the amount of excess ligand. Here we review evidence
regarding the use of OptiMARK over Omniscan for prevention of NSF and perform a
pharmacokinetic-based simulation to determine if the presented evidence is
consistent with the established kinetics of GBCAs and Gd.
PMID- 28501083
TI - The Gastric Microbiome and Its Influence on Gastric Carcinogenesis: Current
Knowledge and Ongoing Research.
AB - Gastric malignancies are a leading cause of cancer-related death worldwide. At
least 2 microbial species are currently linked to carcinogenesis and the
development of cancer within the human stomach. These include the bacterium
Helicobacter pylori and the Epstein-Barr virus. In recent years, there has been
increasing evidence that within the human gastrointestinal tract it is not only
pathogenic microbes that impact human health but also the corresponding
autochthonous microbial communities. This article reviews the gastrointestinal
microbiome as it relates primarily to mechanisms of disease and carcinogenesis
within the upper gastrointestinal tract.
PMID- 28501082
TI - A High-Content Screening Technology for Quantitatively Studying Podocyte
Dynamics.
AB - Podocytes form the visceral layer of a kidney glomerulus and express a
characteristic octopus-like cellular architecture specialized for the
ultrafiltration of blood. The cytoskeletal dynamics and structural elasticity of
podocytes rely on the self-organization of highly interconnected actin bundles,
and the maintenance of these features is important for the intact glomerular
filtration. Development of more differentiated podocytes in culture has
dramatically increased our understanding of the molecular mechanisms regulating
podocyte actin dynamics. Podocytes are damaged in a variety of kidney diseases,
and therapies targeting podocytes are being investigated with increasing efforts.
Association between podocyte damage and disease severity-or between podocyte
recovery and the performance of therapeutic molecules-have been the venues of
research for years. In this perspective, more standardized high--content
screening has emerged as a powerful tool for visualization and analysis of
podocyte morphology. This high-throughput fluorescence microscopy technique is
based on an automated image analysis with simultaneous detection of various
phenotypes (multiplexing) across multiple phenotypic parameters
(multiparametric). Here, we review the principles of high-content screening
technology and summarize efforts to carry out small compound screen using
podocytes.
PMID- 28501084
TI - Barrett Esophagus and Intramucosal Esophageal Adenocarcinoma.
AB - Barrett esophagus (BE) is a precursor lesion for esophageal adenocarcinoma (EAC).
Developments in imaging and molecular markers, and endoscopic eradication
therapy, are available to curb the increase of EAC. Endoscopic surveillance is
recommended, despite lack of data. The cancer risk gets progressively downgraded,
raising questions about the understanding of risk factors and molecular biology
involved. Recent data point to at least 2 carcinogenic pathways operating in EAC.
The use of p53 overexpression and high-risk human papillomavirus may represent
the best chance to detect progressors. Genome-wide technology may provide
molecular signatures to aid diagnosis and risk stratification in BE.
PMID- 28501085
TI - Staging in Esophageal and Gastric Cancers.
AB - Gastric and esophageal tumors have a poor prognosis; approximately 15% of
patients are alive at 10 years following diagnosis. Surgical resection plus
adjunctive chemotherapy or chemoradiotherapy is curative in approximately 50% of
patients with operable disease, but is also associated with significant
morbidity. Therefore, accurate preoperative staging is required to spare patients
unnecessary toxicity and futile surgery. This review evaluates the sensitivity
and specificities of the modalities used to stage patients with gastroesophageal
cancer. Staging techniques reviewed include CT, PET, MRI, EUS, and laparoscopy.
The article concludes with suggestions on appropriate staging tools according to
site and stage of disease.
PMID- 28501086
TI - Management of Locally Advanced Gastroesophageal Cancer: Still a Multidisciplinary
Global Challenge?
AB - The outcome of patients with locally advanced, resectable gastric cancer, or
adenocarcinoma of the gastroesophageal junction is poor. In clinical trials,
multimodality therapy, such as perioperative chemotherapy, preoperative or
postoperative chemoradiation, or adjuvant chemotherapy led to significant
increments in survival. Therefore, experts agree that patients with stage II or
III disease should be offered a multidisciplinary treatment approach. However,
patients are treated somewhat differently in the different regions of the world
and survival rates remain far from being satisfactory. Efforts to further improve
outcome are highly warranted.
PMID- 28501087
TI - The Role of Radiotherapy in Localized Esophageal and Gastric Cancer.
AB - Multimodality management has become a core treatment principle for locally
advanced esophageal, gastroesophageal junction (GEJ), and gastric cancer.
Radiotherapy serves an important role for optimizing patient outcomes. This
article reviews the evolving role of radiotherapy in the multidisciplinary
management of esophageal, GEJ, and gastric cancer, summarizing the results of
recent clinical trials leading to contemporary accepted treatment approaches. A
major theme is the evidence supporting the role of radiotherapy in combined
modality management, particularly the trend toward its delivery in the
neoadjuvant setting. Also reviewed are novel radiotherapy paradigms and newer
radiation technologies such as image-guided radiotherapy and MRI-guided
radiotherapy.
PMID- 28501088
TI - Management of Metastatic Gastric Cancer.
AB - Metastatic gastric cancer is an incurable disease. Systemic chemotherapy prolongs
survival, improves symptom control, and helps maintain a better quality of life
of patients with metastatic gastric cancer. HER2 testing of the primary tumor
and/or the metastases is warranted before initiation of first-line treatment.
This review article outlines the indication and clinical data of medical
treatment of advanced gastric cancer and highlights aspects of quality of life.
PMID- 28501089
TI - The Evolving Role of Checkpoint Inhibitors in the Management of Gastroesophageal
Cancer.
AB - The connection between inflammation and malignancy has long been recognized in
gastric and esophageal cancers. Given the considerable success of immune
checkpoint inhibitors in other tumor types, for example, lung cancer and
melanoma, much attention is being paid to furthering their role in gastric and
esophageal cancers. The Cancer Genome Atlas has provided further details of the
molecular heterogeneity of these tumors, which may help predict responsiveness to
immune checkpoint inhibitors. This article discusses the rationale for
investigating these agents in gastroesophageal cancer and summarizes the relevant
clinical trial data and ongoing studies.
PMID- 28501090
TI - Antiangiogenic Therapy in Gastroesophageal Cancer.
AB - Antiangiogenesis therapy is one of only 2 biologically targeted approaches shown
to improve overall survival over standard of care in advanced adenocarcinoma of
the stomach or gastroesophageal junction (GEJ). Therapeutic targeting of vascular
endothelial growth factor receptor 2 improves overall survival in patients with
previously treated advanced gastric/GEJ adenocarcinoma. No antiangiogenesis
therapy has demonstrated an overall survival benefit in patients with chemo-naive
or resectable esophagogastric cancer or in patients whose tumors arise from the
esophagus. Promising ongoing clinical investigations include the combination of
antiangiogenesis therapy with immune checkpoint inhibition and anti-human
epidermal growth factor receptor 2 therapy.
PMID- 28501093
TI - Future Directions in Improving Outcomes for Patients with Gastric and Esophageal
Cancer.
AB - "This issue of Hematology/Oncology Clinics of North America provides an update to
the current understanding of the physiology of gastric and esophageal cancers and
the state-of-the-art management of disease. Over the past 10 years, we have
witnessed dramatic changes in both our understanding of the disease and its
management. We have 2 new biological agents approved to treat advanced disease,
with several more prospects under development. In this article, the author looks
to the future, attempting to answer the question of which advancements will play
the biggest role in improving patient outcomes in this still-devastating disease.
PMID- 28501092
TI - Emerging Novel Therapeutic Agents in the Treatment of Patients with
Gastroesophageal and Gastric Adenocarcinoma.
AB - With further understanding of the biology of gastric and gastroesophageal
adenocarcinomas, strides are being made to find effective treatments through
novel trial designs. This article focuses on the ongoing trials of drugs
targeting specific hallmarks of gastric and gastroesophageal cancers, including
oncogene addiction proliferative pathways (fibroblast growth factor receptor 2
amplified tumors), stem cell inhibition, apoptotic induction through claudin
inhibitors, and matrix metalloproteinase inhibition. In developing novel
therapeutics in treatment of patients with gastroesophageal adenocarcinomas,
parallel research efforts to refine target population and biomarkers are crucial,
and targeting the tumor genomics and microenvironment may be key in improving
overall survival.
PMID- 28501091
TI - Update on Gastroesophageal Adenocarcinoma Targeted Therapies.
AB - Gastroesophageal cancer (GEC) remains a major cause of cancer-related mortality
worldwide. Although the incidence of distal gastric adenocarcinoma (GC) is
declining in the United States, proximal esophagogastric junction adenocarcinoma
(EGJ) incidence is rising. GC and EGJ, together, are treated uniformly in the
metastatic setting as GEC. Overall survival in the metastatic setting remains
poor, with few molecular targeted approaches having been successfully
incorporated into routine care to date-only first-line anti-HER2 therapy for
ERBB2 amplification and second-line anti-VEGFR2 therapy. This article reviews
aberrations in epidermal growth factor receptor, MET, and ERBB2, their
therapeutic implications, and future directions in targeting these pathways.
PMID- 28501094
TI - The Management of Esophagogastric Cancers Enters a New Era.
PMID- 28501095
TI - Imaging of IgG4-related disease of the head and neck.
AB - IgG4-related disease is a systemic, inflammatory disorder typically involving
multiple organ systems. Several eponymous conditions described previously in the
clinical and radiology literature are now recognised to be part of the IgG4
related disease spectrum. This includes multiple manifestations in the head and
neck region, which are the subject of this review. Imaging can occasionally
suggest the specific diagnosis of IgG4 disease. More commonly, it will be
included in a limited differential diagnosis that requires clarification with the
aid of image-guided biopsy. There are strict histopathological criteria for the
diagnosis of IgG4-related disease.
PMID- 28501096
TI - Combined diffusion-weighted imaging and dynamic contrast-enhanced MRI for
differentiating radiologically indeterminate malignant from benign orbital
masses.
AB - AIM: To evaluate the performance of the combination of diffusion-weighted (DW)
and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for
differentiating radiologically indeterminate malignant from benign orbital
masses. MATERIALS AND METHODS: Sixty-five patients with orbital masses (36 benign
and 29 malignant) underwent DW and DCE MRI examinations for pre-treatment
evaluation. The apparent diffusion coefficient (ADC) was derived from DW imaging
data using the mono-exponential model. The volume transfer constant (Ktrans), the
flux rate constant between the extravascular extracellular space and the plasma
(Kep), and the extravascular extracellular volume fraction (Ve) were calculated
using modified Tofts model. Differences in quantitative metrics were tested using
independent-samples t test. Receiver operating characteristic (ROC) curve
analyses were used to determine and compare the diagnostic ability of each
significant metric. RESULTS: The malignant group demonstrated significantly lower
ADC (0.711+/-0.260 versus 1.187+/-0.389, p<0.001) and higher Kep values (1.265+/
0.637 versus 0.871+/-0.610, p=0.008) than the benign group. Optimal diagnostic
performance (area under the ROC curve [AUC], 0.941; sensitivity, 0.966;
specificity, 0.917) could be achieved using combined ADC and Kep values as the
diagnostic index. The diagnostic performance of the combination of ADC and Kep
was significantly better than Kep alone (p=0.006). Compared with ADC alone,
combined ADC and Kep values also showed higher AUC (0.941 versus 0.898), although
the difference did not reach statistical significance (p=0.220). CONCLUSION: Kep
and ADC could help to differentiate radiologically indeterminate malignant from
benign orbital masses. The combination of DW and DCE MRI might improve the
differentiating performance.
PMID- 28501097
TI - Orofacial pain and headaches associated with exfoliation glaucoma.
AB - BACKGROUND AND OVERVIEW: Exfoliation syndrome is the most common identifiable
cause of open-angle glaucoma. The authors report a case of exfoliation glaucoma
in a patient who had orofacial pain. CASE DESCRIPTION: A 77-year-old woman was
treated at the orofacial pain clinic for left-sided facial pain and headaches of
7 months' duration. Her cataracts and open-angle glaucoma had been diagnosed
approximately 3 years earlier. Her main symptoms were orofacial pain, eye
redness, inflammation of the eyelids, and eyelid edema. Magnetic resonance
imaging showed no evidence of intracranial or extracranial pathology. Hemicrania
continua was considered as a possible diagnosis. Indomethacin was prescribed but
did not affect her headaches. She then went to an ophthalmologist to rule out
secondary headaches. Intraocular pressure was 13 millimeters of mercury in the
right eye and 67 mm Hg in the left eye. The ophthalmologist made a diagnosis of
exfoliation glaucoma, and the patient underwent surgical treatment for the
glaucoma and cataracts. After surgery, she was free of symptoms, and intraocular
pressure was 15 mm Hg in the left eye. CONCLUSIONS AND PRACTICAL IMPLICATIONS:
During differential diagnosis, dentists need to consider intraoral and systemic
conditions that can mimic odontogenic or orofacial pain disorders in the
patient's medical history and that have a higher incidence associated with the
patient's age.
PMID- 28501098
TI - Alterations in intestinal microbiota relate to intestinal failure-associated
liver disease and central line infections.
AB - BACKGROUND: The gut microbiota plays a vital role in modulating the metabolic and
immune functions of the intestines. We aimed to analyze the dysbiosis of
microbiota in infants with short bowel syndrome (SBS) with different
complications. PROCEDURE: We included 26 fecal samples from 18 infants with SBS
during parenteral nutrition. The samples were categorized into three groups:
asymptomatic, parenteral nutrition-associated liver disease (PNALD), and central
line-associated bloodstream infection (CLABSI). Seven healthy infants were
enrolled as controls. Fecal microbiota, secretory IgA, calprotectin, bile acids,
and short chain fatty acids were detected. RESULTS: The bacterial diversity of
the Asymptomatic and Control Groups was significantly higher than that in the
PNALD and CLABSI Groups. Proteobacteria was the most pronounced phylum in the
PNALD and CLABSI Groups. Decreased acetate was observed in all SBS samples;
however, fecal secretory IgA and calprotectin and the proportion of primary and
secondary bile acids did not differ from those in healthy controls. CONCLUSIONS:
Marked alterations of the intestinal microbiota with decreased level of acetate
were shown in SBS patients compared with healthy controls. Over-abundance of
Proteobacteria (especially Enterobacteriaceae) was found in the samples from the
PNALD and CLABSI Groups. LEVEL OF EVIDENCE: Prognosis Study, Level I.
PMID- 28501099
TI - Entropy of aqueous surfaces. Application to polymeric Langmuir films.
AB - Measuring surface (excess) entropies provides a bounty of valuable structural
information that is hard to obtain otherwise. In the paper these quantities are
defined and procedures of measurements discussed. Mostly they involve
measurements at different temperatures. A review is given for interfaces with
aqueous solutions in the absence of polymers. This review illustrates how,
sometimes unanticipated, pieces of information are obtained, for example with
cloud seeding and a possible explanation of the Jones-Ray effect. As a novel
extension the procedure is applied to deposited, or Langmuir, monolayers of
poly(ethylene oxide)-poly(propylene oxide) block copolymers. It will be shown how
the various phase transitions and associated configurations of these polymers can
be recognized and monitored.
PMID- 28501100
TI - Comparison of Direct Current Synchronized Cardioversion to Ibutilide-Guided
Catheter Ablation for Long-Term Sinus Rhythm Maintenance After Isolated Pulmonary
Vein Isolation of Persistent Atrial Fibrillation.
AB - Use of the antiarrhythmic ibutilide after isolated pulmonary vein isolation (PVI)
might distinguish atrial remodeling severity and cases requiring further
substrate modification, thereby improving efficacy of persistent atrial
fibrillation (AF) treatment. Ninety-six consecutive patients with persistent AF
were randomized after PVI to either direct current synchronized cardioversion
(DCC group, n = 48) or 1 mg of intravenous ibutilide (ibutilide group, n = 48)
followed by no further intervention if AF converted to sinus rhythm (SR) within
30 minutes (ibutilide conversion subgroup) or by complex fractionated atrial
electrogram (CFAE) ablation until SR recovery or complete CFAE elimination
(ibutilide nonconversion subgroup). With similarly distributed baseline
characteristics and no serious postablation complications, the primary end point
of 12-month SR maintenance rate after PVI was significantly higher for ibutilide
versus the DCC group before (75% vs 56%; p = 0.042) or after (83% vs 60%; p =
0.011) reablation at physician's discretion for recurrence beyond 3 months after
PVI. After ibutilide administration, 21 of 48 patients (44%) converted to SR at
17 +/- 8 minutes (mean +/- SD); those in the ibutilide nonconversion subgroup had
larger atrial size (47 +/- 4 vs 45 +/- 4; p = 0.025) and CFAE area (29 +/- 8 vs
12 +/- 5; p = 0.001) and longer AF duration (27 +/- 6 vs 21 +/- 10; p = 0.026).
Among ibutilide conversion and nonconversion subgroups and DCC group, procedure,
ablation, and x-ray exposure times differed significantly, as did 12-month SR
maintenance rate before (81% vs 70% vs 56%; p = 0.043) or after reablation (86%
vs 81% vs 60%; p = 0.042). In conclusion, in persistent AF treatment, ibutilide
guided ablation after PVI yields higher 1-year SR maintenance rate than PVI only.
PMID- 28501101
TI - Risk assessment: A hindrance or a help to landfill management?
PMID- 28501102
TI - Integration of biological effects, fish histopathology and contaminant
measurements for the assessment of fish health: A pilot application in Irish
marine waters.
AB - This study investigates the use of a weight of evidence (WOE) approach to
evaluate fish health status and biological effects (BEs) of contaminants for
assessment of ecosystem health and discusses its potential application in support
of the Marine Strategy Framework Directive (MSFD). External fish disease, liver
histopathology and several BEs of contaminant exposure including 7-ethoxy
resorufin O-de-ethylase (EROD), acetylcholinesterase (AChE), bile metabolites,
vitellogenin (VTG) and alkali labile phosphates (ALP) were measured in two
flatfish species from four locations in Ireland. Contaminant levels in fish were
generally low with PCBs in fish liver below OSPAR environmental assessment
criteria (EAC). There were consistencies with low PCB levels, EROD and PAH bile
metabolite levels detected in fish. Dab from Cork, Dublin and Shannon had the
highest relative prevalence of liver lesions associated with the carcinogenic
pathway. An integrated biomarker response (IBR) showed promise to be useful for
evaluation of environmental risk, although more contaminant parameters in liver
are required for a full assessment with the present study.
PMID- 28501103
TI - mRNA decay is regulated via sequestration of the conserved 5'-3' exoribonuclease
Xrn1 at eisosome in yeast.
AB - We describe a novel mechanism of mRNA decay regulation, which takes place under
the conditions of glucose deprivation in the yeast Saccharomyces cerevisiae. The
regulation is based on temporally stable sequestration of the main 5'-3' mRNA
exoribonuclease Xrn1 at the eisosome, a plasma membrane-associated protein
complex organizing a specialized membrane microdomain. As documented by
monitoring the decay of a specific mRNA substrate in time, Xrn1-mediated mRNA
degradation ceases during the accumulation of Xrn1 at eisosome, but the eisosome
associated Xrn1 retains its functionality and can be re-activated when released
to cytoplasm following the addition of glucose. In cells lacking the eisosome
organizer Pil1, Xrn1 does not associate with the plasma membrane and its activity
is preserved till the stationary phase. Thus, properly assembled eisosome is
necessary for this kind of Xrn1 regulation, which occurs in a liquid culture as
well as in a differentiated colony.
PMID- 28501104
TI - Knockdown of Cbp/P300-interacting transactivator with Glu/Asp-rich carboxy
terminal domain 2 inhibits cell division and increases apoptosis in gastric
cancer.
AB - BACKGROUND: Cbp/P300-interacting transactivator with Glu/Asp-rich carboxy
terminal domain 2 (CITED2) is a pleiotropic protein associated with numerous cell
functions, including transcription and differentiation. The role of CITED2 has
been investigated in a number of malignancies; however, the roles of this protein
in gastric cancers remain unclear. Therefore, we determined the role of CITED2 in
gastric cancers. MATERIALS AND METHODS: Gastric cancer cell lines (MKN74, MKN28,
7901, and AGS) were used to assess CITED2 transcript levels. Messenger RNA levels
were determined using quantitative polymerase chain reaction. Lentiviral vectors
containing CITED2 small interfering RNA were used to knockdown CITED2 expression.
Cell proliferation was assessed with fluorescent imaging and 3-(4,5
dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide assays. Apoptosis and cell
cycle stages were assessed through flow cytometry, and formation of colonies was
determined using a fluorescent microscope. RESULTS: All cell lines tested in this
study expressed CITED2. The cell line expressing the highest levels of CITED2
(MKN74) showed significant knockdown of endogenous CITED2 expression on
lentiviral infection. Cell proliferation was shown to be lower in CITED2
knockdown MKN74 cells. G1/S-phase cell cycle arrest was observed on silencing of
CITED2 in MKN74 cells. A significant increase in apoptosis was observed on CITED2
knock down in MKN74 cells, while colony forming ability was significantly
inhibited after knock down of CITED2. CONCLUSIONS: CITED2 supports gastric cancer
cell colony formation and proliferation while inhibiting apoptosis making it a
potential gene therapy target for gastric cancer.
PMID- 28501105
TI - Surviving rectal cancer: examination of racial disparities surrounding access to
care.
AB - BACKGROUND: The aim of this study was to evaluate whether survival differences
are attributable to disproportionate access to stage-specific rectal cancer
treatment recommended by the National Comprehensive Care Network. METHODS: A
retrospective analysis of the National Cancer Data Base between 1998 and 2006 was
performed. A series of Kaplan-Meier survival analyses were used to compare 5-y
survival among race cohorts. Propensity score matching was used to compare
Caucasian and African American patients who received the same treatment by
accounting for covariates. RESULTS: 5-y overall survival in African Americans was
50.7% versus 56.2% in Caucasians (P < 0.001). In patients with stage I-III
disease, 5-y survival was 58.7% in African Americans versus 63.1% in Caucasians
(P < 0.001). Analysis of patients receiving surgery for stage I-III disease,
revealed a 61.1% 5-y survival in African Americans versus 65.8% in Caucasians (P
< 0.001). Propensity score matching did not eliminate the racial disparity. The
median survival for Caucasian patients was 109.6 mo as compared to 85.8 mo for
African Americans (P < 0.001). CONCLUSIONS: These data show that access to
standard care appears to decrease but not eliminate the survival differences
between African Americans and Caucasians with rectal cancer.
PMID- 28501106
TI - Concurrent endocrine and other surgical procedures: an institutional experience.
AB - INRODUCTION: The number of endocrine procedures, specifically parathyroidectomy,
thyroidectomy, and adrenalectomy, being performed is increasing. There is a
paucity of literature on the feasibility of combining these procedures with other
surgical procedures. Therefore, the aim of this study was to determine the effect
of performing concurrent surgical procedures on postoperative outcomes. METHODS:
This is a single institution retrospective review of multiple prospectively
maintained databases of patients who underwent elective thyroidectomy,
parathyroidectomy, and/or adrenalectomy in combination with another procedure.
The other procedures included soft tissue, breast or hernia, abdominal major,
abdominal minor, cervical, and "other". Demographics, operative details, length
of-stay, and 30-d outcomes were reviewed. "Endocrine-specific" complications
included recurrent laryngeal nerve injury, hypoparathyroidism, cervical wound
infection, hematoma, and other. RESULTS: The cohort comprised 104 patients.
Overall, 19 (18%) patients had 21 complications, including endocrine-specific
complications in eleven (11%) patients. These eleven complications included
recurrent laryngeal nerve injury (n = 3; 3%), hematoma (n = 2; 2%), wound
infection (n = 1; 1%), transient hypoparathyroidism (n = 2; 2%), and other (n =
3; 3%). The remaining complications included three (3%) general complications,
six (6%) patients with complications related to the concurrent procedure, and one
patient who underwent an open adrenalectomy and hysterectomy and developed a
midline wound dehiscence, which could not be specifically attributed to either
procedure. CONCLUSIONS: Less than 5% of patients undergoing a surgical endocrine
procedure underwent a concurrent procedure, ranging from soft tissue to major
abdominal. Short-term endocrine-specific complications were managed safely,
suggesting that concurrent procedures can be considered, with minimal effect on
patient outcomes.
PMID- 28501107
TI - Melatonin reduces changes to small intestinal microvasculature during systemic
inflammation.
AB - BACKGROUND: Systemic inflammation is known to impair the microcirculation in
intestine and other organs as a result of multifactorial events. Here, we show
that melatonin selectively reduces changes to the small intestinal
microvasculature during systemic inflammation. MATERIALS AND METHODS:
Lipopolysaccharide (LPS) was infused at a rate of 0.5 mg/kg * h to induce
systemic inflammation in male Wistar rats. Melatonin (single dose: 3 mg/kg * 15
min) was intravenously administered before as well as 120 and 240 min after the
beginning of the LPS infusion. Systemic parameters were determined in regular
intervals. Small intestine, liver, and kidney were histologically (structure of
the microvessels, intravascular blood accumulation, and hemorrhages) and
immunohistochemically (mast cells, granulocytes, and macrophages) analyzed.
RESULTS: Continuous infusion of LPS resulted in dilated microvessels with
intravascular blood accumulation (congestion) in liver and small intestine, the
latter being particularly pronounced. Blood vessel walls remained intact, there
were no hemorrhages. Melatonin significantly reduced these changes to the
microvasculature in small intestine, but not in liver. It further reduced mast
cell and granulocytes count in small intestine enhanced by LPS. However, except
for the systemic blood pressure, melatonin neither improved LPS-dependent changes
to systemic parameters nor mortality. CONCLUSIONS: Changes to the
microvasculature during systemic inflammation are most pronounced in small
intestine. Melatonin selectively diminishes these changes to small intestinal
microvasculature, probably by reducing the local immune cells recruitment.
However, changes to the small intestine are not decisive for the survival. We
assume that the therapeutic benefit of melatonin is more likely in local
intestinal inflammation.
PMID- 28501108
TI - Vendor effects on murine gut microbiota influence experimental abdominal sepsis.
AB - BACKGROUND: Experimental animal models are indispensable components of
preclinical sepsis research. Reproducible results highly rely on defined and
invariant baseline conditions. Our hypothesis was that the murine gut microbiota
varies among different distributors of laboratory animals and that these
variations influence the phenotype of abdominal sepsis derived from a bacterial
inoculum model (intraperitoneal stool injection). MATERIALS AND METHODS: Male
C57BL/6 mice (8-wk old) purchased from Charles River (CR), Janvier (J), and
Harlan (H) were sacrificed, and the bacterial composition of feces was analyzed
using CHROMagar orientation medium. Stool was injected intraperitoneally into CR
mice, followed by clinical observation and gene expression analysis. Experiments
were repeated 16 mo later under the same conditions. RESULTS: Stool analysis
revealed profound intervendor differences in bacterial composition, mainly
regarding Staphylococcus aureus and Bacillus licheniformis. Mice challenged with
CR as well as H feces developed significantly higher severity of disease and died
within the observation period, whereas stool from J mice did not induce any of
these symptoms. Real-time polymerase chain reaction revealed corresponding
results with significant upregulation of proinflammatory cytokines and vascular
leakage-related mediators in CR and H injected animals. Sixteen months later, the
bacterial fecal composition had significantly shifted. The differences in
clinical phenotype of sepsis after intraperitoneal stool injection had vanished.
CONCLUSIONS: We are the first to demonstrate vendor and time effects on the
murine fecal microbiota influencing sepsis models of intraabdominal stool
contamination. The intestinal microbiota must be defined and standardized when
designing and interpreting past and future studies using murine abdominal sepsis
models.
PMID- 28501109
TI - Sarcopenia: a new predictor of postoperative complications for elderly gastric
cancer patients who underwent radical gastrectomy.
AB - BACKGROUND: A geriatric assessment is needed to identify high-risk elderly
patients with gastric cancer. However, the current geriatric assessment has been
considered to be either time-consuming or subjective. The present study aimed to
investigate the predictive effect of sarcopenia on the postoperative
complications for elderly patients who underwent radical gastrectomy. MATERIALS
AND METHODS: We conducted a prospective study of patients who underwent radical
gastrectomy from August 2014 to December 2015. Computed tomography-assessed
lumbar skeletal muscle, handgrip strength, and gait speed were measured to define
sarcopenia. RESULTS: Sarcopenia was present in 69 of 240 patients (28.8%) and was
associated with lower body mass index, lower serum albumin, lower hemoglobin, and
higher nutritional risk screening 2002 scores. Postoperative complications
significantly increased in the sarcopenic patients (49.3% versus 24.6%, P <
0.001), compared with nonsarcopenic patients. The multivariate analysis
demonstrated that sarcopenia (odds ratio: 2.959, 95% CI: 1.629-5.373, P < 0.001)
and the Charlson comorbidity index >=2 (odds ratio: 3.357, 95% CI: 1.144-9.848, P
= 0.027) were independent risk factors for postoperative complications.
CONCLUSIONS: Sarcopenia, presented as a new geriatric assessment factor, was a
strong and independent risk factor for postoperative complications of elderly
patients with gastric cancer.
PMID- 28501110
TI - Arachidonic acid causes hidden blood loss-like red blood cell damage through
oxidative stress reactions.
AB - BACKGROUND: Hidden blood loss (HBL) often occurs in the prosthetic replacement
for joint, but the mechanism is still not clear. MATERIALS AND METHODS: This
study tried to establish an animal model of HBL by injecting arachidonic acid
(AA) into the Sprague-Dawley rats. Different concentrations of AA were injected
into the tail veins of the rats, and blood samples were collected before and
after administration at 24, 48, and 72 h. A complete blood count was obtained by
to find the hemoglobin (Hb) and red blood cell (RBC) count changes. The
glutathione peroxidase (GSH-PX) and total superoxide dismutase (T-SOD) activities
and hydrogen peroxide (H2O2) levels were detected. The morphological changes of
erythrocyte were observed under a polarizing microscope. The absorbance values of
the blood samples were tested to determine the presence of ferryl Hb. RESULTS:
HBL occurred in the experimental groups when the concentration of AA reached 10
mmol/L; Hb and RBC values decreased sharply at 24- and 48-h postinjection. This
was followed by reduced activities of GSH-PX and T-SOD and decreased levels of
H2O2. Moreover, the pathologic changes of red cell morphology mainly presented as
pleomorphic RBC morphology, including cell rupture. The absorbance values of the
blood samples were in accordance with ferryl Hb features. RBC and Hb values were
relatively stable at 72 h. The GSH-PX and T-SOD activities and H2O2 levels
gradually increased up to a balanced state. CONCLUSIONS: The study concluded that
high concentrations of AA can induce oxidative stress reactions in the body,
causing acute injury of RBCs, which is closely related to HBL.
PMID- 28501111
TI - Laparoscopic dissection and division of distal fistula in boys with rectourethral
fistula.
AB - BACKGROUND: Congenital rectourethral fistula (RUF) is the most common form of
anorectal malformations found in boys. The aim of this study is to review our
experience with dissection and division of distal fistula using laparoscopic
surgery in the management of RUF, especially rectourethral bulbar fistula.
METHODS: One hundred and two consecutive boys with congenital RUF who underwent
conventional or single-incision laparoscopic surgery between July 2008 and June
2015 were enrolled in the study. The dissection of the distal fistula was
performed along submucosal layer to a level 0.5 cm proximal to the urethra.
Rectal mucosa of the fistula was dissected to the distal most point and
completely transected flush with the posterior urethra. The residual muscular
cuff was ligated with Hem-o-Lock clip or 5-0 PDS suture. Voiding
cystourethrography and pelvic magnetic resonance imaging were performed at 3 mo,
6 mo, and 1 y postoperatively. RESULTS: All patients successfully underwent
laparoscopic surgery without conversion. The mean age at the time of operation
was 4.3 +/- 2.9 mo. The operative times for the rectoprostatic fistula and
rectobulbar fistula were similar (118.2 versus 119.4 min, P = 0.082). There was
no significant difference in average operative time between conventional
laparoscopic surgery group and single-incision laparoscopic surgery group (118.8
versus 119.1 min, P = 0.281). There was no injury to the urethra or vas deferens.
The urethral catheter was removed on postoperative day 10. All patients were
followed up. The median follow-up period was 3.3 +/- 1.8 y. No recurrent fistula
or urethral diverticulum was detected on voiding cystourethrography and pelvic
MRI at 1 y. CONCLUSIONS: Submucosal dissection and division of distal fistula
using a laparoscopic approach is safe, feasible, and effective for congenital
RUF, especially bulbar fistula, in boys.
PMID- 28501112
TI - Early results of a surgeon-led, perioperative surgical home.
AB - BACKGROUND: The Perioperative Surgical Home is a novel care model designed to
provide patient-centered, high-quality surgical care. In 2013, we implemented
POSH, a pilot Peri-Operative Surgical Home at Phoenix Indian Medical Center
(PIMC), an Indian Health Service hospital, as a quality improvement project.
After 2 y, we sought to quantify the impact of POSH on the quality of surgical
care at PIMC. MATERIALS AND METHODS: We conducted a retrospective review of 33
surgical patients who underwent surgery at PIMC through the POSH process between
2013 and 2015 matched to 64 historical controls with similar operations. Study
patients underwent surgery via the POSH treatment process. Primary outcomes were
composite measures of (1) care standards and (2) care goals. Success was defined
as meeting seven of nine care standards and six of eight care goals. RESULTS AND
DISCUSSION: The mean number of care standards met was 8.1 +/- 1.0 versus 4.2 +/-
1.4 (P < 0.001) and the mean number of care goals met was 6.7 +/- 0.8 versus 6.1
+/- 1.1 (P = 0.005) for POSH patients and historical controls, respectively.
Patients participating in the POSH model were 8.6 (95% confidence interval: 3.5
22.3) and 1.5 (95% confidence interval: 1.2-1.9) times more likely to meet the
minimum number of care standards and goals, respectively. Fourteen of the study
patients (42%) would not have been offered surgery at PIMC before POSH due to
elevated surgical risk. CONCLUSIONS: POSH may have improved quality of surgical
care at PIMC while expanding services to more complex patients. POSH may present
an opportunity for improved surgical quality in resource-constrained
environments.
PMID- 28501113
TI - Clinical Acuity Shorthand System: a standardized classification tool to
facilitate handoffs.
AB - BACKGROUND: The handoff of medical information from one provider to another can
be inefficient and error prone, potentially undermining patient safety. Although
several tools for structuring handoffs exist, none provide a brief, standardized
framework for ensuring that patient acuity is efficiently and reliably
communicated. We aim to introduce and perform initial testing of the Clinical
Acuity Shorthand System (CLASS) (Copyright 2015, Duke University. All rights
reserved.) for surgery, a patient classification tool intended to facilitate
efficient communication of key patient information during handoffs. MATERIALS AND
METHODS: Surgical trainees at a single center were asked to perform an exercise
involving application of CLASS to 10 theoretical patient scenarios and to then
complete a brief survey. Responses were scored based on similarity to target
answers. Performance was evaluated overall and between groups of trainees. Time
required to complete the exercise was also determined and perceived utility of
the system was assessed based on survey responses. RESULTS: The study task was
completed by 17 participants. Mean time to task completion was 10.3 +/- 8.4 min.
Accuracy was not decreased, and was in fact superior, in junior trainees. Most
respondents indicated that such a system would be feasible and could prevent
medical errors. CONCLUSIONS: CLASS is a novel system that can be learned quickly
and implemented readily by trainees and can be used to convey patient information
concisely and with acceptable fidelity regardless of level of training. Further
study examining application of this system on clinical surgical services is
warranted.
PMID- 28501114
TI - Evaluation of palliative care training and skills retention by medical students.
AB - BACKGROUND: Training in palliative and end-of-life care has been introduced in
medical education; however, the impact of such training and the retention of
skills and knowledge have not been studied in detail. This survey study examines
long-term follow-up on end-of-life communication skills training, evaluation, and
skills retention in medical students. MATERIALS AND METHODS: During the surgical
clerkship, all third-year medical students received communication skills training
in palliative care using simulated patients. The training involved three
scenarios involving diverse surgical patients with conditions commonly
encountered during the surgical clerkship. The students used web-based best
practice guidelines to prepare for the patient encounters. The following
communication abilities were evaluated: (1) giving bad news clearly and with
empathy, (2) initiating death and dying conversations with patients and/or their
family members, (3) discussing do not resuscitate status and exploring
preferences for end-of-life care, and (4) initiating conversations regarding
religious or spiritual values and practices. All students were surveyed after 1
year (12-24 mo) to ascertain: (1) the retention of skills and/or knowledge gained
during this training, (2) application of these skills during subsequent clinical
rotations, and (3) overall perception of the value added by the training to their
undergraduate medical education. These results were correlated with residency
specialty choice. RESULTS: The survey was sent to all graduating fourth-year
medical students (n = 105) in our program, of which 69 students responded to the
survey (66% response rate). All respondents agreed that palliative care training
is essential in medical school training. Seventy percent of the respondents
agreed that the simulated encounters allowed development of crucial conversation
skills needed for palliative/end-of-life care communications. The most useful
part of the training was the deliberate practice of "giving bad news" (85%). Most
of the respondents (80%) indicated retention of overall communication skills with
regard to approach and useful phrases. Forty-five percent claimed retention of
communication skills surrounding death and dying, and 44% claimed retention of
end-of-life preferences/advance directives/do not resuscitate. Relatively few
respondents (16%) retained skills regarding religious or spiritual values. There
was no correlation between training evaluation/skill retention and the area of
residency specialty the students pursued on graduation. CONCLUSIONS: Early
training in palliative and end-of-life care communication is feasible and
effective during the surgical clerkship. Students highly valued the simulated
patient and/or family discussions and retained most of the skills and knowledge
from the experiential simulated encounters. However, students felt the skills
developed could be reinforced with opportunities to observe their attending
physicians or residents leading such discussions and involving students in such
discussions as and when appropriate.
PMID- 28501115
TI - Postconditioning attenuates coronary perivascular and interstitial fibrosis
through modulating angiotensin II receptors and angiotensin-converting enzyme 2
after myocardial infarction.
AB - BACKGROUND: Postconditioning (Postcon) is known to reduce infarct size. This
study tested the hypothesis that Postcon attenuates the perivascular and
interstitial fibrosis after myocardial infarction through modulating angiotensin
II-activated fibrotic cascade. MATERIALS AND METHODS: Male Sprague-Dawley rats
were subjected to 45-min coronary occlusion followed by 1 and 6 wk of
reperfusion. Postcon was applied at the onset of reperfusion with four cycles of
10/10-s reperfusion-ischemia at the onset of reperfusion. Preconditioning
(Precon) with two cycles of 5/5-min ischemia-reperfusion was applied before
coronary occlusion. RESULTS: Postcon reduced angiotensin-converting enzyme
protein and expression in the perivascular area and intermyocardium, coincident
with the less-expressed angiotensin II receptor, type 1, enhanced angiotensin II
receptor, type 2, and angiotensin converting enzyme 2. Postcon lowered the
monocyte chemoattractant protein-1 and inhibited the populations of interstitial
macrophages (60 +/- 12 versus 84 +/- 9.5 number per high-powered field [HPF] in
control, P < 0.05). Along with these modulations, Postcon also downregulated
transforming growth factor beta1 protein and inhibited proliferation of alpha
smooth muscle actin expressing myofibroblasts (41 +/- 11 versus 79 +/- 8.2 number
per HPF in control, P < 0.05), consistent with downregulated phospho-Smad2 and
phospho-Smad3. Furthermore, the synthesis of collagen I and III was attenuated,
and the perivascular-interstitial fibrosis was inhibited by Postcon as
demonstrated by reduced perivascular fibrosis ratio (0.6 +/- 0.6 versus 1.6 +/-
0.5 per HPF in control, P < 0.05) and smaller collagen-rich area (16 +/- 4.7
versus 34 +/- 9.2% per HPF in control, P < 0.05). Precon conferred a comparable
level of protection as Postcon did in all parameters measured, suggesting
protection trigged by this endogenous stimulation can be achieved when it was
applied either before ischemia or after reperfusion. CONCLUSIONS: These results
suggest that Postcon could be selected as an adjunctive intervention with other
existing therapeutic drugs to treat the fibrosis-derived heart failure patients
after myocardial infarction.
PMID- 28501116
TI - Usefulness of virtual reality in assessment of medical student laparoscopic
skill.
AB - BACKGROUND: This study evaluates if undergraduate medical trainees' laparoscopic
skills acquisition could be assessed using a virtual reality (VR) simulator and
how the resultant metrics correlate with performance of Fundamentals of
Laparoscopic Surgery (FLS) tasks. Our hypothesis is that the VR simulator metrics
will correlate with passing results in a competency-based curriculum (FLS).
MATERIALS AND METHODS: Twenty-eight fourth-year medical students applying for
surgical residency were recruited to participate in a VR training curriculum
comprised of camera navigation, hand eye coordination, and FLS tasks: circle
cutting (CC), ligating loop (LL), peg transfer (PT), and intracorporeal knot
tying (IKT). Students were given 8 wk to achieve proficiency goals, after which
they were observed performing FLS tasks. The ability of the VR simulator to
detect penalties in each of the FLS tasks and correlations of time taken to
complete tasks are reported. RESULTS: Twenty-five students trained in all
components of the curriculum. All students were proficient in camera navigation
and hand eye coordination tasks. Proficiency was achieved in CC, LL, PT, and IKT
by 21, 19, 23, and one student, respectively. VR simulation showed high
specificity for predicting zero penalties on the observed CC, LL, and PT tasks
(80%, 75%, and 80%, respectively). CONCLUSIONS: VR can be used to assess medical
student's acquisition of laparoscopic skills. The absence of penalties in the
simulator reasonably predicts the absence of penalties in all FLS skills, except
IKT. The skills acquired by trainees can be used in residency for further
monitoring of progress toward proficiency.
PMID- 28501117
TI - Institutional variation in surgical care for early-stage breast cancer at
community hospitals.
AB - BACKGROUND: There is significant institutional variation in the surgical care of
breast cancer, and this may reflect access to services and resultant physician
practice patterns. In previous studies, specialty care has been associated with
variation in the operative treatment of breast cancer but has not been evaluated
in a community setting. This study investigates these issues in a cohort of 59
community hospitals in the United States. MATERIALS AND METHODS: Data on patients
receiving an operation for breast cancer (2006-2009) in a large, geographically
diverse cohort of hospitals were obtained. Administrative data, autoabstracted
cancer-specific variables from free text, and multiple other data sets were
combined. Polymotous logistic regression with multilevel outcomes identified
associations between these variables and surgical treatment. RESULTS: At 59
community hospitals, 4766 patients underwent breast conserving surgery (BCS),
mastectomy, or mastectomy with reconstruction. The older patients were most
likely to receive mastectomy alone, whereas the younger age group underwent more
reconstruction (age <50), and BCS was most likely in patients aged 50-65.
Surgical procedure also varied according to tumor characteristics. BCS was more
likely at smaller hospitals, those with ambulatory surgery centers, and those
located in nonmetropolitan areas. The likelihood of reconstruction doubled when
there were more reconstructive surgeons in the health services area (P = 0.02).
BCS was more likely when radiation oncology services were available within the
hospital or network (P = 0.04). CONCLUSIONS: Interpretation of these results for
practice redesign is not straightforward. Although access to specialty care is
statistically associated with type of breast surgical procedure, clinical impact
is limited. It may be more effective to target other aspects of care to ensure
each patient receives treatment consistent with her individual preferences.
PMID- 28501118
TI - Impact of chromogranin A, differentiation, and mitoses in nonfunctional
pancreatic neuroendocrine tumors <= 2 cm.
AB - BACKGROUND: Small pancreatic neuroendocrine tumors (PNETs) are a unique subset of
pancreatic neoplasms. Chromogranin A (CgA) levels, mitotic rate, and histologic
differentiation are often used to characterize PNET behavior. This study
evaluates the impact of these factors on survival in patients with PNETs.
METHODS: The US National Cancer Data Base (1998-2012) was reviewed for patients
with stages I-III, nonfunctional PNETs <=2 cm. Clinicopathologic characteristics
were collected, and univariate and multivariate survival analyses were performed.
RESULTS: Of 1159 patients, 872 had tumor differentiation recorded, 403 had
mitotic rate, and 217 patients had CgA. Mitotic rate >20 mitoses per 10 high
power microscopic fields was significantly associated with survival (hazard ratio
[HR] = 10.6, P = 0.002) in multivariate analysis. Of those who underwent
resection, there was no significant difference in positive lymph nodes between
high (>100 ng/mL) and low (<=100 ng/mL) CgA levels (0.27 versus 0.37, P =
0.4440). Multivariate analyses of patients with both grade and CgA recorded found
poorly differentiated tumors and very high CgA (>400 ng/mL) negatively impacted
survival (HR = 2.99, P < 0.0001, HR = 3.47, P < 0.0001, respectively). Propensity
score matching demonstrated improved 5-y survival in patients who underwent
surgical resection, P < 0.0001. CONCLUSIONS: Poorly differentiated disease should
be considered an indicator of worse prognosis in nonfunctional PNETs <=2 cm.
Surgical resection appears to improve survival in these patients.
PMID- 28501119
TI - Nonocclusive mesenteric infarction after cardiac surgery: potential biomarkers.
AB - BACKGROUND: Nonocclusive mesenteric ischemia can cause intestinal infarction but
the diagnosis is challenging. This prospective study evaluated three plasma
biomarkers of intestinal infarction after cardiac surgery. MATERIALS AND METHODS:
Patients were recruited after cardiac surgery if they required laparotomy (with
or without intestinal resection) for suspected nonocclusive mesenteric ischemia.
Plasma levels of D-lactate, intestinal fatty acid-binding protein (i-FABP), and
smooth muscle actin (SMA) before laparotomy were measured. RESULTS: Twenty
patients were recruited (68 +/- 9 y, EuroSCORE: 8.7 +/- 2.8, mortality 70%). A
positive laparotomy (n = 13) was associated with no change in D-lactate (P =
0.95), decreased i-FABP (P = 0.007), and increased SMA (P = 0.01). All patients
with high SMA had a positive laparotomy. A subgroup analysis was undertaken in
the eight patients who required multiple laparotomies. D-lactate increased
between the two laparotomies in nonsurvivors (n = 4). Plasma i-FABP (P = 0.008)
and SMA (P = 0.036) significantly decreased after the bowel resection, regardless
of survival outcome. CONCLUSIONS: None of the biomarkers were accurate enough to
reliably diagnose intestinal infarction. However, all patients with high values
of SMA developed intestinal infarction, thus warranting further investigation. An
increasing D-lactate after intestinal resection suggests impending death.
PMID- 28501120
TI - Histologic lung cancer subtype differentiates synchronous multiple primary lung
adenocarcinomas from intrapulmonary metastases.
AB - BACKGROUND: Distinguishing synchronous multiple primary lung cancers (SMPLCs)
from intrapulmonary metastases is important. The objective of this study was to
determine long-term survival in patients who underwent surgical resection for
synchronous multiple lung cancers and identify additional criteria that may be
useful to distinguish patients with SMPLCs from those with more advanced disease.
METHODS: The medical records of patients with lung cancer who underwent planned
resection for synchronous multiple lung cancers from 2007 to 2012 at our
institutions were reviewed retrospectively. A comprehensive histologic assessment
was used to determine whether the tumors were metastases or separate synchronous
primary tumors. RESULTS: A total of 51 patients with synchronous multiple lung
cancers underwent surgical resection. Twenty-nine patients had ipsilateral
synchronous multiple lung cancers, and 22 had bilateral synchronous multiple lung
cancers. No perioperative death occurred. The survival analysis of all 51
patients with synchronous multiple lung cancers who underwent planned resection
of all lesions showed 3- and 5-year overall survival rates of 86% and 67%,
respectively, The median overall survival was not reached. The comprehensive
histologic assessment identified six patients with intrapulmonary metastasis and
45 patients with SMPLCs. Intrapulmonary metastases were associated with decreased
survival. Among patients with SMPLCs, the epidermal growth factor receptor
mutation distribution shown high concordant frequency rate of 35% (5/14).
CONCLUSIONS: Survival after surgical resection of synchronous multiple lung
cancers in different lobes was promising. A comprehensive histologic assessment
was useful for differentiating SMPLCs from intrapulmonary metastases.
PMID- 28501121
TI - Validation of a field spinal motion restriction protocol in a level I trauma
center.
AB - BACKGROUND: Spinal motion restriction (SMR) after traumatic injury has been a
mainstay of prehospital trauma care for more than 3 decades. Recent guidelines
recommend a selective approach with cervical spine clearance in the field when
criteria are met. MATERIALS AND METHODS: In January 2014, the Department of
Health Services of the City of Los Angeles, California, implemented revised
guidelines for cervical SMR after blunt mechanism trauma. Adult patients (aged
>=18 y) with an initial Glasgow Coma Scale (GCS) score of >=13 presented to a
single level I trauma center after blunt mechanism trauma over the following 1-y
period were retrospectively reviewed. Demographics, injury data, and prehospital
data were collected. Cervical spine injury (CSI) was identified by International
Classification of Disease, Ninth Revision, codes. RESULTS: Emergency medical
services transported 1111 patients to the emergency department who sustained
blunt trauma. Patients were excluded if they refused c-collar placement or if
documentation was incomplete. A total of 997 patients were included in our
analysis with 172 (17.2%) who were selective cleared of SMR per protocol. The
rate of Spinal Cord Injury was 2.2% (22/997) overall and 1.2% (2/172) in patients
without SMR. The sensitivity and specificity of the protocol are 90.9% (95%
confidence interval: 69.4-98.4) and 17.4% (95% confidence interval: 15.1-20.0),
respectively, for CSI. Patients with CSI who arrived without immobilization
having met field clearance guidelines, were managed without intervention, and had
no neurologic compromise. CONCLUSIONS: Guidelines for cervical SMR have high
sensitivity and low specificity to identify CSI. When patients with injuries were
not placed on motion restrictions, there were no negative clinical outcomes.
PMID- 28501123
TI - Attenuation of intestinal ischemia-reperfusion-injury by beta-alanine: a
potentially glycine-receptor mediated effect.
AB - BACKGROUND: Acute mesenteric ischemia is often caused by embolization of the
mesenteric arterial circulation. Coherent intestinal injury due to ischemia and
following reperfusion get visible on macroscopic and histologic level. In
previous studies, application of glycine caused an ameliorated intestinal damage
after ischemia-reperfusion in rats. Because we speculated that glycine acted here
as a signal molecule, we investigated whether the glycine-receptor agonist beta
alanine evokes the same beneficial effect in intestinal ischemia-reperfusion.
MATERIALS AND METHODS: beta-alanine (10, 30, and 100 mg/kg) was administered
intravenously. Ischemia/reperfusion of the small intestine was initiated by
occluding and reopening the superior mesenteric artery in rats. After 90 min of
ischemia and 120 min of reperfusion, the intestine was analyzed with regard to
macroscopic and histologic tissue damage, the activity of the saccharase, and
accumulation of macrophages. In addition, systemic parameters and metabolic ones
(e.g., acid-base balance, electrolytes, and blood glucose) were measured at
certain points in time. RESULTS: All three dosages of beta-alanine did not change
systemic parameters but prevent from hyponatremia during the period of
reperfusion. Most importantly, application of 100-mg beta-alanine clearly
diminished intestinal tissue damage, getting visible on macroscopic and
histologic level. In addition, I/R-mediated decrease of saccharase activity and
accumulation of macrophages in the small intestine were ameliorated. CONCLUSIONS:
The present study demonstrated that beta-alanine was a potent agent to ameliorate
I/R-induced injury of the small intestine. Due to its diminishing effect on the
accumulation of macrophages, beta-alanine is strongly expected to mediate its
beneficial effect via glycine receptors.
PMID- 28501122
TI - Association of patient age with high-risk pathologic features in papillary
thyroid cancer.
AB - BACKGROUND: Certain patient demographics and histopathologic features are risk
factors for papillary thyroid cancer (PTC) recurrence after initial treatment.
Our objective was to determine whether very young age is associated with
aggressive pathologic features in patients with PTC. MATERIALS AND METHODS: A
retrospective analysis was performed for PTC patients who underwent surgical
treatment at the University of Michigan between 2006 and 2012. Patients with
known distant metastases were excluded. Demographics, high-risk pathologic
features (capsular or vascular invasion, extrathyroidal extension, lymph node
metastases, and extranodal extension), and disease recurrence were analyzed.
RESULTS: 632 PTC patients were included in the analysis. Median age was 49 y
(range 10-87). Tumors in patients aged <25 y had higher rates of extranodal
extension (P = 0.002) compared with patients aged 25-44 y. Patients aged <25 y
had more vascular invasion (P < 0.001) and lymph node metastasis (P = 0.001) than
tumors in patients aged between 45-75 y. Patients aged >75 y had higher rates of
vascular invasion (P < 0.001) and extrathyroidal extension (P = 0.001) compared
with patients aged 45-75 y and more extrathyroidal extension (P < 0.001) than
patients aged 25-44 y. There were no differences in tumor characteristics between
the <25 and >75 age groups. CONCLUSIONS: PTC patients aged <25 y of age or older
than 75 y exhibit higher rates of aggressive histopathologic features compared to
PTC patients aged between 25-75 y.
PMID- 28501124
TI - Effects of endotoxin absorber hemoperfusion on microcirculation in septic pigs.
AB - BACKGROUND: Endotoxins contribute to systemic inflammatory response and
microcirculatory dysfunctions under conditions of sepsis. Polymyxin B
hemoperfusion (PMX-HP) is used to remove circulating endotoxins and improve
clinical outcomes. This study aims to investigate the effect of PMX-HP on
microcirculation in septic pigs. MATERIALS AND METHODS: By using a septic pig
model, we tested the hypothesis that PMX-HP can correct intestinal
microcirculation, tissue oxygenation saturation, and histopathologic alterations.
A total of 18 male pigs were divided into three groups: (1) sham; (2) sepsis
(fecal peritonitis); and (3) sepsis + PMX-HP groups. A sidestream dark field
video microscope was used to record microcirculation throughout the terminal
ileal mucosa, colon mucosa, kidney surface, and sublingual area. A superficial
tissue oxygenation monitor employing the light reflectance spectroscopy technique
was used to measure the tissue oxygen saturation. Hematoxylin and eosin staining
was used for histologic examination. RESULTS: The perfused small vessel density
and tissue oxygen saturation of the ileal mucosa at 6 h were higher in the sepsis
+ PMX-HP group than those in the sepsis group. The fluid amount and
norepinephrine infusion rate between the sepsis group and sepsis + PMX-HP groups
did not differ significantly. The histologic score for the ileal mucosa was lower
in the sepsis + PMX-HP group than that in the sepsis group. Finally, the urine
output was higher in the sepsis + PMX-HP group than it was in the sepsis group.
CONCLUSIONS: This study demonstrates that PMX-HP attenuates microcirculatory
dysfunction, tissue desaturation, and histopathologic alterations in the ileal
mucosa in septic pigs.
PMID- 28501125
TI - Direct orthotopic implantation of hepatic organoids.
AB - BACKGROUND: Liver organoids show potential for development as a tissue
replacement therapy for patients with end-stage liver disease, but efficient
methods for introducing organoids into host livers have not been established. In
this study, we aimed to develop a surgical technique to implant hepatic organoids
into the liver and assess their engraftment. METHODS: Donor hepatocytes were
isolated from ROSA26 C57BL/6 mice, so that engrafted cells, when implanted into
wild-type mice, could be easily identified by X-gal staining. Hepatic organoids
were generated by three-dimensional culture in rotating wall vessel bioreactors.
We qualitatively and quantitatively compared organoid engraftment to that of
single-cell hepatocyte transplants. In addition, we determined the effect of
adding stellate cells to hepatocytes to form co-aggregated organoids and the
effect of partial hepatectomy of the host liver on organoid engraftment. RESULTS:
Direct orthotopic implantation of hepatic organoids within a hepatotomy site
resulted in local engraftment of exogenous hepatocytes with limited durability.
Hepatocyte-stellate cell organoids produced more extracellular matrix but did not
significantly improve engraftment compared with hepatocyte-alone organoids.
Partial hepatectomy of the host liver led to significantly decreased engraftment
of organoids. Survival of organoids was limited by the presence of apoptotic
hepatocytes within organoids as early as 1 h after implantation. Organoids
eventually became necrotic and elicited a chronic inflammatory giant cell
reaction similar to a foreign body response. CONCLUSIONS: With additional
organoid and host factor optimization, direct orthotopic implantation of hepatic
organoids may be an approach to introduce large numbers of exogenous hepatocytes
into recipient livers.
PMID- 28501126
TI - Perceptions regarding helmet use: a cross-sectional survey of female pillions in
Karachi, Pakistan.
AB - BACKGROUND: In 2011, road traffic injury-associated fatalities among motorized
two-wheeler (MTW) pillion riders (backseat two-wheeler passengers) rose 30% in
Karachi. Despite mandatory helmet laws, helmet use fell 20% the same year. This
study aims to identify opinions of female pillions on helmet usage and whether
various forms of media influence their self-perception. METHODS: Trained
surveyors, using a survey tool used in similar studies in South Asia, conducted
random, man-on-the-street interviews of 400 women in four areas of Karachi. Data
pertaining to demographics, opinions on helmet laws, media influences, and helmet
usage were collected. Data were analyzed in SAS 9.3 using chi-squared or Fisher's
exact tests. RESULTS: Of the 400 women, 98.8% (n = 394) reported never wearing a
helmet while riding on a MTW as a pillion rider. Women with a postsecondary or
higher (US ninth grade) education level were more likely to be aware of helmet
laws (38.6%) than women with lower education levels (24.6%, P = 0.005). Most
women (82.4%, n = 329) supported mandatory laws and 97% (n = 289) recognized that
disability was the more likely to result than death in event of a traumatic brain
injury. Nearly all (98.5%, n = 394) stated that they would use a helmet if they
were men, regardless of age, education level, or employment status. Television
news was the most influential media form (83.7%, n = 334), with most women
finding it effective because of its informative nature (91.3%, n = 303).
CONCLUSIONS: Most Pakistani women do not personally use helmets when riding MTWs,
yet most believe helmet use should be legally required for MTW riders and
drivers. These data show that media outlets such as television can be used as a
platform to educate the public about helmet usage, which may lead to improved
helmet compliance among female MTW pillions in Pakistan. Furthermore,
investigations into improved helmet comfort and appearance by collaborating with
helmet manufacturers may have a positive impact on helmet use in Pakistan.
PMID- 28501127
TI - C-C motif chemokine 22 ligand (CCL22) concentrations in sera of gastric cancer
patients are related to peritoneal metastasis and predict recurrence within one
year after radical gastrectomy.
AB - BACKGROUND: Gastric cancer is a common cancer with a poor prognosis. Chemokines
play important roles in the tumor microenvironments to support tumor growth and
metastasis. The effects of C-C motif chemokine ligand 22 (CCL22) in gastric
cancer remain unclear. MATERIALS AND METHODS: Between January 1, 2014 and April
31, 2014, a total of 298 gastric cancer patients were recruited to this study.
Circulating concentrations of CCL22 were measured in gastric cancer patients
before surgery, at discharged and during follow-up visits. The expression of
CCL22 in gastric cancer tumor beds was measured by immunohistochemistry. The
proportion of CD3+CD4+CD25+Foxp3+ regulatory T cells in tumor sites was assessed
by flow cytometry. RESULTS: Gastric cancer patients had higher serum CCL22 levels
compared to healthy controls (P < 0.001). Immunohistochemistry indicated that the
gastric cancer tumor beds were the source of serum CCL22, as gastric cancer
patients had an increased proportion of strong expression of CCL22 (P < 0.01),
and immunohistochemistry scores were positively correlated with levels of
circulating CCL22 (P < 0.001). Gastric cancer tissue harbored a higher percentage
of regulatory T cells compared to normal tumor-free stomach margins (P < 0.001),
and this abundance of regulatory T cells was positively correlated with
circulating levels of CCL22 (P < 0.001). Gastric cancer patients with peritoneal
metastasis showed increased levels of circulating CCL22 before surgery compared
to metastasis-free patients (P < 0.001). Gastric cancer patients with the
recurrence within the first year after surgery had elevated serum CCL22
concentrations at different time points compared to those of recurrence-free
patients (P < 0.001). Logistic regression analysis indicated that high CCL22
circulating levels before surgery is a risk factor for peritoneal metastasis and
an independent risk factor for an early recurrence after surgery. CONCLUSIONS:
CCL22 plays an important role in supporting gastric cancer development presumably
by increasing the percentage of regulatory T cells in the tumor
microenvironments. CCL22 levels in sera have a predictive value for gastric
cancer peritoneal metastasis and the early recurrence. Therefore, CCL22 may be a
therapeutic target for gastric cancer.
PMID- 28501128
TI - Immunochemotherapy benefits in gastric cancer patients stratified by programmed
death-1 ligand-1.
AB - BACKGROUND: Effectiveness of protein-bound polysaccharide K (PSK) during adjuvant
chemotherapy in gastric cancer patients expressing programmed death-1 ligand 1
(PD-L1) has not been investigated. Investigating this might help in triaging
candidates eligible to immunochemotherapy. MATERIALS AND METHODS: In total, 918
patients with stages II and III gastric cancer, undergoing curative gastrectomy,
and receiving adjuvant chemotherapy were enrolled in a prospective database, and
the patients were retrospectively reviewed. We classified those patients into
four cohorts stratified by PD-L1 expression and PSK administration, namely PD-L1,
PSK (-,+); PD-L1, PSK (-,-); PD-L1, PSK (+,+); and PD-L1, PSK (+,-). In addition,
another independent cohort of 20 patients undergoing radical gastrectomy was
prospectively recruited to check their immunological cells of sera before and 2
mo after PSK administration. RESULTS: PSK treatment was an independent prognostic
factor for patient's overall survival (P = 0.020), whereas PD-L1 expression per
se was not. Administration of PSK prolonged patient survival in stages IIIA and
IIIB (P = 0.031) but not in stage II or stage IIIC. Patients with negative
expression of PD-L1, treated with PSK had longer survival than those not treated
with PSK (P = 0.033). PSK did not affect the survival of patients with positive
expression of PD-L1, (P = 0.421). The percentages of natural killer and natural
killer T (NKT) cells, but not Th1, Th17, Treg, or IFN-gamma+/CD8+ T cells, were
significantly increased in PD-L1 (-) patients treated with PSK. However, these
findings were not evident in PD-L1 (+) patients. CONCLUSIONS: PSK treatment
preferentially confers a survival gain for patients with stage IIIA/IIIB gastric
cancer, especially in the PD-L1 (-) subpopulation.
PMID- 28501129
TI - Loss of muscle mass: a significant predictor of postoperative complications in
acute diverticulitis.
AB - BACKGROUND: Severe muscle mass depletion, sarcopenia, has been shown to be
associated with poor operative outcomes. However, its impact on emergency
abdominal operations remains unclear. The purpose of this study was to examine
the association between low muscle mass (LMM) and outcomes after emergency
operations for acute diverticulitis. PATIENTS AND METHODS: Patients >=18 y
requiring an emergency operation for acute diverticulitis between January 2007
and September 2014 were included. On preoperative computed tomography, the cross
sectional area (CSA) and transverse diameter (TVD) of the right and left psoas
muscle were measured at the level of the third lumbar vertebral body. Sensitivity
analysis was performed to determine appropriate CSA and TVD cutoff values
defining low skeletal muscle mass. Clinical outcomes of patients with low muscle
mass (LMM group) were compared with the non-LMM group. RESULTS: A total of 89
patients met our inclusion criteria. Median CSA and TVD were 794 mm2 and 24 mm,
respectively. There was a strong correlation between the CSA and TVD (R2 = 0.84).
In univariable analysis, significantly higher rates of postoperative major
complications (63% versus 37%, P = 0.027) and surgical site infection (47% versus
19%, P = 0.008) were identified in the LMM group. After adjusting for clinically
important covariates in a logistic regression model, patients with LMM were
significantly associated with higher odds of major complications and surgical
site infection. CONCLUSIONS: Preoperative assessment of the psoas muscle CSA and
TVD on computed tomography can be a practical method for identifying patients at
risk for postoperative complications.
PMID- 28501131
TI - MicroRNA-203 promotes liver regeneration after partial hepatectomy in cirrhotic
rats.
AB - BACKGROUND: Liver resection or partial hepatectomy (PH) is still the most
commonly used therapeutic option for hepatocellular carcinoma (HCC) at present.
However, the impaired regenerative ability induced by the accompanied liver
cirrhosis is an important risk factor of posthepatectomy liver failure, and
posthepatectomy liver failure is a feared complication that accounts for up to
75% of mortality after extensive liver resection. MicroRNA(miR)-203 is a tumor
suppressor of HCC and may act as a positive intermediary in A20-enhanced
interleukin (IL-6)/signal transducer and activator of transcription 3 (STAT3) pro
proliferative signals, which may promote liver regeneration after PH. However,
its direct pro-proliferative effect on cirrhotic liver after hepatectomy is
unknown. MATERIALS AND METHODS: Liver cirrhosis was induced by intraperitoneal
injection of 50% CCl4-olive oil solution in adult male Wistar rat. Rats with
liver cirrhosis received portal vein injection of physiological saline, miR-203
lentivirus, or control empty lentivirus, and then 70% PH was performed under
ether anesthesia 7 d later. Liver samples were harvested at 0, 24, 36, and 72 h
after 70% PH. Hepatic expressions of cyclin D1 and Ki67 were checked to evaluate
the liver regenerative ability. Hepatic expressions of IL-6, suppressor of
cytokine signaling 3 (SOCS3), and phospho-STAT3 were also tested to clarify the
mechanisms of miR-203 in liver regeneration. RESULTS: The regeneration of miR-203
overexpression cirrhotic liver after 70% PH was enhanced and peaked at 24 and 36
h after 70% PH. The cyclin D1-positive liver cells/high-power field (HPF) in miR
203 overexpression liver markedly increased at 24 and 36 h after 70% PH compared
with 0-h samples. When comparing with the control groups, cyclin D1-positive
liver cells/HPF in miR-203 overexpression liver were also significantly increased
at 24 and 36 h after 70% PH. A similar result of the Ki67-positive liver
cells/HPF was achieved at 36 h after 70% PH. The hepatic expression of IL-6
showed a rising tendency after 70% PH, and the levels of IL-6 are significantly
higher in miR-203 overexpression livers. Hepatic expression of SOCS3 was
negatively expressed with hepatic miR-203 expression level, and the reduced
expression of SOCS3 facilitated the phosphorylation of STAT3. CONCLUSIONS: By
targeting SOCS3 and then enhancing proliferating IL-6/STAT3 signaling pathway,
hepatic overexpression of miR-203 can facilitate the initiation of liver
regeneration and enhance the potency of liver regeneration after 70% PH in
cirrhotic rat. Together with the tumor suppressive effect on HCC, miR-203 would
be an ideal candidate for promoting liver regeneration in HCC patients undergoing
liver resection without the risk of tumorigenesis or cancer recurrence.
PMID- 28501130
TI - Collateral artery pathways of the femoral and popliteal artery.
AB - BACKGROUND: The role of collateral artery circulation in the lower limb is under
debate but clinically relevant, particularly when using covered stents for
occlusive disease. Covered stents seem to outperform nitinol stents in extensive
disease, but collaterals could be essential in case of acute thrombosis. In the
present study, we describe the collateral pathways of the deep and superficial
femoral artery (DFA, SFA) and the popliteal artery (PA), observed in human
cadavers. METHODS: Ten fresh frozen cadaver legs were selected. The SFA and DFA
were separately cannulated and injected with a different colored latex mixture
simultaneously. After curing of the latex, the circulation was dissected thus
visualizing the main arteries and their collateral vessels. The process was
photographed and recorded, and collateral pathways were analyzed using a
standardized vessel segmentation. The upper leg was divided in three regions,
that is, the femoral triangle (F), the adductor canal (H), and the popliteal
fossa (P) that, in turn, were split in three segments (1, 2, and 3, from proximal
to distal). RESULTS: Overall, 113 collateral vessels were found; 69 originated
from the DFA, 34 from the SFA, and 10 from the PA. The majority of collaterals
originating from the DFA terminated in the SFA (57%). Fifty-six of 113
collaterals (50%) ended in either the distal adductor channel (H3) or the
proximal PA (P1). Another 28 collateral arteries (25%) had their origin in this
segment (H3, P1) and mostly connected to the P2 and P3 segments. Forty-three
collaterals of the DFA and H3 segment had a direct or indirect connection to
below the knee muscles. CONCLUSIONS: The majority of collaterals originate from
the DFA, and the greater part of all collaterals has a connection with the H3-P1
segment. This observation may have clinical implications in the planning of
endovascular procedures.
PMID- 28501132
TI - Association between climatic elements and acute appendicitis in Japan.
AB - BACKGROUND: In Japan, it has been reported that an increase in atmospheric
pressure is associated with a higher incidence of acute appendicitis. The aim of
this epidemiologic study was to investigate the association between climatic
elements and the incidence of acute appendicitis. MATERIALS AND METHODS: A case
crossover design was used in the present study. Two wk before diagnosis was used
for the target period. The same 2-wk period, but 1, 2, and 3 y before diagnosis,
was used for the control period. The study participants were patients with acute
appendicitis (10-29 y) from 14 facilities in the Greater Tokyo Area. Mean of the
observed values for atmospheric pressure, temperature, relative humidity, and
hours of sunshine calculated for each target and control period were used as
climatic elements to investigate trends 1 and 2 wk before diagnosis. RESULTS: The
year of diagnosis, a statistically significant moderate upward trend in
atmospheric pressure was observed during the 2-wk period before diagnosis of
acute appendicitis (tau = 0.47; P = 0.0213), whereas a weak nonsignificant
downward trend was observed 1 y before diagnosis (tau = -0.29; P = 0.1596), and
weak nonsignificant upward trends were observed 2 (tau = 0.24; P = 0.2505) and 3
y (tau = 0.28; P = 0.1634) before diagnosis. CONCLUSIONS: An association was
found between atmospheric pressure and the incidence of acute appendicitis.
However, no significant differences were found in relation to sex or age. These
findings suggest that changes in atmospheric pressure are associated with the
likelihood of patients visiting the hospital.
PMID- 28501133
TI - Intraintestinal administration of ulinastatin protects against sepsis by
relieving intestinal damage.
AB - BACKGROUND: Intravenous administration of ulinastatin (UTI), a broad spectral
protease inhibitor, has been used on an experimental basis with severe sepsis
patients in Asia. However, the effects of intraintestinal administration of UTI
on intestinal and multiple organ damage in sepsis have not been reported.
MATERIALS AND METHODS: In this study, we established a sepsis model in rats using
cecal ligation and puncture and compared the effects of intraintestinal
administration of UTI through an artificial fistula of duodenum and
intraperitoneal administration of UTI on the pathophysiological changes of
sepsis. RESULTS: It was found that intraintestinal administration of UTI (1)
significantly improved the survival of septic rats, (2) significantly reduced the
serum levels of tumor necrosis factor-alpha, interleukin-1beta, interleukin-6 as
well as intestinal injury biomarkers diamine oxidase, D-lactic acid, and
fluorescein isothiocyanate-dextran 4, and (3) significantly reduced intestinal
microscopic and ultrastructural damage of septic rats. In addition, the
protective effects of intraintestinal administration of UTI were significantly
better than those of intraperitoneal administration of UTI. CONCLUSIONS: Overall,
the present study for the first time revealed that intraintestinal administration
of protease inhibitor UTI could reduce systemic inflammatory responses and
multiple organ dysfunction in rats with sepsis by inhibiting autodigestion of
intestinal wall due to proteases and provided new research ideas and experimental
evidences for treatment of sepsis by intraintestinal administration of UTI.
PMID- 28501135
TI - Impact of hernia volume on pulmonary complications following complex hernia
repair.
AB - BACKGROUND: Despite a multitude of evidence-based prediction models and risk
factors for postoperative complications after ventral hernia repair, estimating a
patient's risk of postoperative complications after ventral hernia repair remains
challenging. In an attempt to improve the preoperative assessment of complex
hernia patients, some studies have examined pulmonary changes after hernia repair
hypothesizing that large hernias lead to pulmonary changes and increased
pulmonary complication rates. Some studies have described a correlation between
hernia volume and pulmonary changes, although none provided compelling evidence
to identify hernia volume as a risk factor for pulmonary complications. This
study evaluates the relationship between hernia volume and postoperative
pulmonary complications using computed tomography (CT)-based volume measurements.
MATERIALS AND METHODS: Analysis of a prospectively maintained database of
consecutive complex hernia patients from 2011 to 2014 undergoing endoscopic
(ECST) or open component separation technique (CST) for a hernia defect with a
minimum width of 6 cm and visual protrusion of the hernia sac ventral of the
rectus abdominis muscles in supine position was performed. Hernia volume was
calculated using multiple plane reconstruction of a standard abdominal CT-scan.
Noted endpoints were pulmonary complications. RESULTS: Thirty-five patients
underwent ECST (n = 20) or CST (n = 15) with a median defect volume of 474 cm3
(range, 114-2086 cm3). Observed complications were pneumonia (n = 4), pulmonary
infiltrate (n = 3), aspiration pneumonia (n = 2), and acute respiratory distress
syndrome (n = 1). Univariate and multivariate analyses showed that pulmonary
complications were associated with "hernia volume" (P = 0.045; 95% CI: 1.008
1.910). CONCLUSIONS: Hernia volume is a promising risk factor for postoperative
pulmonary complications and can be calculated using a standard abdominal CT-scan.
PMID- 28501134
TI - Factors associated with palliative care use in patients undergoing cytoreductive
surgery and hyperthermic intraperitoneal chemotherapy.
AB - BACKGROUND: Peritoneal carcinomatosis represents widespread metastatic disease
throughout the abdomen and/or pelvis. Cytoreductive surgery/hyperthermic
intraperitoneal chemotherapy (CRS/HIPEC) improves the overall survival compared
to standard therapy alone. The role palliative care (PC) plays however, remains
poorly studied among these patients. METHODS: Patients who had previously
undergone HIPEC and who underwent an inpatient admission from 7/1/2013 to
6/30/2014 were identified to determine which patients were referred for inpatient
or outpatient palliative consultation. Multivariable logistic regression analysis
was performed to identify risk factors associated with the use of PC. RESULTS: Of
the 60 patients analyzed, 23 (38.3%) had a PC consultation with a median time to
PC referral of 310 (IQR: 151-484 days). Patients who were prescribed opioids (no
PC referral versus PC referral: 46.0% versus 91.3%, P < 0.001), patients who
reported the use of a cancer-related emetic (35.1% versus 87.0%, P < 0.001),
patients reporting the use of total parenteral nutrition (16.2% versus 39.1%, P =
0.046), and patients dependent on a gastric tube for nutrition (5.4% versus
43.5%, P < 0.001) were more likely to be referred to a PC consultation. On
multivariable analysis, use of opioids, use of a cancer-related antiemetic, and
the use of a G-tube were independently associated with a greater odds for being
referred to PC (all P < 0.05). CONCLUSIONS: Approximately one-third of patients
were referred to PC following cytoreductive surgery/hyperthermic intraperitoneal
chemotherapy. Palliative care referrals were most commonly used for patients with
chronic symptoms, which are difficult to manage, especially toward the end of
life.
PMID- 28501136
TI - Delayed splenic vascular injury after nonoperative management of blunt splenic
trauma.
AB - BACKGROUND: Delayed splenic vascular injury (DSVI) is traditionally considered a
rare, often clinically occult, harbinger of splenic rupture in patients with
splenic trauma that are managed conservatively. The purpose of our study was to
assess the incidence of DSVI and associated features in patients admitted with
blunt splenic trauma and managed nonoperatively. MATERIALS AND METHODS: A
retrospective analysis was conducted over a 4-y time. Patients admitted with
blunt splenic trauma, managed no-operatively and with a follow-up contrast
enhanced computed tomography (CT) scan study during admission were included. The
CT scans were reviewed for American Association for the Surgery of Trauma splenic
injury score, amount of hemoperitoneum, and presence of DSVI. Logistic regression
models were used to investigate the risk factors associated with DSVI. RESULTS: A
total of 100 patients (60 men and 40 women) constituted the study group. Follow
up CT scan demonstrated a 23% incidence of DSVI. Splenic artery angiography
validated DSVI in 15% of the total patient population. Most DSVIs were detected
only on arterial phase CT scan imaging. The American Association for the Surgery
of Trauma splenic injury score (odds ratio = 1.73; P = 0.045) and the amount of
hemoperitoneum (odds ratio = 1.90; P = 0.023) on admission CT scan were
associated with the development of DSVI on follow-up CT scan. CONCLUSIONS: DSVI
on follow-up CT scan imaging of patients managed nonoperatively after splenic
injury is common and associated with splenic injury score assessed on admission
CT scan.
PMID- 28501137
TI - Supinator to ulnar nerve transfer via in situ anterior interosseous nerve bridge
to restore intrinsic muscle function in combined proximal median and ulnar nerve
injury: a novel cadaveric study.
AB - BACKGROUND: In cases of high ulnar nerve palsy, result of nerve repair in term of
intrinsic muscle recovery is unsatisfactory. Distal nerve transfer can diminish
the regeneration time and improve the results. But, there was no perfect distal
nerve transfer for restoring intrinsic hand function in combined proximal median
and ulnar nerve injuries. This cadaveric study aims to evaluate the possibility
and feasibility of supinator nerve transfer to motor branch of ulnar nerve (MUN).
METHODS: Ten cadaveric upper limbs dissected to identify the location of the
supinator branch, anterior interosseous nerve (AIN), and MUN. The AIN was cut
from its origin and transferred to the supinator branches. Also, the AIN was
distally cut and transferred to the MUN. After nerve coaptation, surface area,
fascicle count, and axon number were determined by histologic methods. RESULTS:
In all limbs, the proximal and distal stumps of AIN reached the supinator branch
and the MUN without tension, respectively. The mean of axon number in the
supinator, proximal stump of AIN, distal stump of AIN and MUN branches were
32,426, 45,542, 25,288, and 35,426, respectively. CONCLUSIONS: This study showed
that transfer of the supinator branches to the MUN is possible via the in situ
AIN bridge. The axon count data showed a favorable match between the supinator
branches, AIN, and MUN. Therefore, it is suggested that this technique can be
useful for patients with combined high median and ulnar nerve injuries.
PMID- 28501138
TI - Submucosal neurons and enteric glial cells expressing the P2X7 receptor in rat
experimental colitis.
AB - The aim of this study was to evaluate the effect of ulcerative colitis on the
submucosal neurons and glial cells of the submucosal ganglia of rats. 2,4,6
Trinitrobenzene sulfonic acid (TNBS; colitis group) was administered in the colon
to induce ulcerative colitis, and distal colons were collected after 24h. The
colitis rats were compared with those in the sham and control groups. Double
labelling of the P2X7 receptor with calbindin (marker for intrinsic primary
afferent neurons, IPANs, submucosal plexus), calretinin (marker for secretory and
vasodilator neurons of the submucosal plexus), HuC/D and S100beta was performed
in the submucosal plexus. The density (neurons per area) of submucosal neurons
positive for the P2X7 receptor, calbindin, calretinin and HuC/D decreased by 21%,
34%, 8.2% and 28%, respectively, in the treated group. In addition, the density
of enteric glial cells in the submucosal plexus decreased by 33%. The profile
areas of calbindin-immunoreactive neurons decreased by 25%. Histological analysis
revealed increased lamina propria and decreased collagen in the colitis group.
This study demonstrated that ulcerative colitis affected secretory and
vasodilatory neurons, IPANs and enteric glia of the submucosal plexus expressing
the P2X7 receptor.
PMID- 28501139
TI - J-ALEX: alectinib versus crizotinib in ALK-positive lung cancer.
PMID- 28501141
TI - TRPV6: From identification to function.
PMID- 28501140
TI - Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung
cancer (J-ALEX): an open-label, randomised phase 3 trial.
AB - BACKGROUND: Alectinib, a potent, highly selective, CNS-active inhibitor of
anaplastic lymphoma kinase (ALK), showed promising efficacy and tolerability in
the single-arm phase 1/2 AF-001JP trial in Japanese patients with ALK-positive
non-small-cell lung cancer. Given those promising results, we did a phase 3 trial
to directly compare the efficacy and safety of alectinib and crizotinib. METHODS:
J-ALEX was a randomised, open-label, phase 3 trial that recruited ALK inhibitor
naive Japanese patients with ALK-positive non-small-cell lung cancer, who were
chemotherapy-naive or had received one previous chemotherapy regimen, from 41
study sites in Japan. Patients were randomly assigned (1:1) via an interactive
web response system using a permuted-block method stratified by Eastern
Cooperative Oncology Group performance status, treatment line, and disease stage
to receive oral alectinib 300 mg twice daily or crizotinib 250 mg twice daily
until progressive disease, unacceptable toxicity, death, or withdrawal. The
primary endpoint was progression-free survival assessed by an independent review
facility. The efficacy analysis was done in the intention-to-treat population,
and safety analyses were done in all patients who received at least one dose of
the study drug. The study is ongoing and patient recruitment is closed. This
study is registered with the Japan Pharmaceutical Information Center (number
JapicCTI-132316). FINDINGS: Between Nov 18, 2013, and Aug 4, 2015, 207 patients
were recruited and assigned to the alectinib (n=103) or crizotinib (n=104)
groups. At data cutoff for the second interim analysis, 24 patients in the
alectinib group had discontinued treatment compared with 61 in the crizotinib
group, mostly due to lack of efficacy or adverse events. At the second interim
analysis (data cutoff date Dec 3, 2015), an independent data monitoring committee
determined that the primary endpoint of the study had been met (hazard ratio 0.34
[99.7% CI 0.17-0.71], stratified log-rank p<0.0001) and recommended an immediate
release of the data. Median progression-free survival had not yet been reached
with alectinib (95% CI 20.3-not estimated) and was 10.2 months (8.2-12.0) with
crizotinib. Grade 3 or 4 adverse events occurred at a greater frequency with
crizotinib (54 [52%] of 104) than alectinib (27 [26%] of 103). Dose interruptions
due to adverse events were also more prevalent with crizotinib (77 [74%] of 104)
than with alectinib (30 [29%] of 103), and more patients receiving crizotinib (21
[20%]) than alectinib (nine [9%]) discontinued the study drug because of an
adverse event. No adverse events with a fatal outcome occurred in either
treatment group. INTERPRETATION: These results provide the first head-to-head
comparison of alectinib and crizotinib and have the potential to change the
standard of care for the first-line treatment of ALK-positive non-small-cell lung
cancer. The dose of alectinib (300 mg twice daily) used in this study is lower
than the approved dose in countries other than Japan; however, this limitation is
being addressed in the ongoing ALEX study. FUNDING: Chugai Pharmaceutical Co,
Ltd.
PMID- 28501142
TI - ?
AB - Jean-Martin Charcot (1825-1893) was the preeminent neurologist of the nineteenth
century. Several of his major contributions remain fully relevant to contemporary
neurology, and this essay highlights three areas of particular importance to the
modern neurologist: the anatomo-clinical method that Charcot developed as the
anchor of neurological study; the integration of new scientific discoveries from
other fields as a core strategy for neurological advancement; and the role of
heredity as the fundamental etiological focus to the understanding of the
pathogenesis of primary neurological disorders. Further, Charcot left a strong
tradition of visual skills as the core requirement for accurate neurological
diagnosis and emphasized scientific humility in the face of difficult diseases.
In spite of vast advances in neuroscience over the 20th and 21st centuries, the
challenges faced by Charcot remain largely the same for the contemporary
neurologist, and the lessons provided by Charcot retain their power and
significance today.
PMID- 28501143
TI - Do we know how to diagnose epilepsy early in Alzheimer's disease?
AB - Epilepsy is an increasingly recognized comorbidity in Alzheimer's disease (AD).
First described as generalized in dementia patients, epileptic AD patients are
nowadays fully described in earlier stages of the disease (with mild or
subjective cognitive impairment). At such early stages, patients may present not
only with generalized seizures, but also with focal seizures (commonly localized
in the frontal or temporal lobe). Thus, partial or generalized epilepsy is part
of the semiological spectrum of AD that should be borne in mind at all stages of
disease to ensure early identification and prevent the risk of repeated seizures
(such as accidents, injury, progression of cognitive impairment). This review of
the available (and still growing) literature shows that there are already
sufficient data to inform physicians on seizure semiology, and on the diagnostic
value of electroencephalography and brain imaging. Taken together, these tools
can help to rapidly identify epilepsy in AD patients. Nevertheless, epilepsy
diagnosis can be challenging, and test medication is sometimes necessary. Some
cerebrospinal fluid biomarkers (or their ratios) may also prove to be good
predictors of seizures in AD, but further studies are needed. Epilepsy in AD
patients is frequently pharmacosensitive, and a good response can be obtained
with standard doses of antiepileptic drugs. For all these reasons and based on
our review of the literature, it appears that, at present, the diagnosis of
epilepsy in AD is not only possible at any stage of the disease, but also to be
recommended to improve the patient's prognosis.
PMID- 28501144
TI - Sequential injection differential pulse voltammetric method based on screen
printed carbon electrode modified with carbon nanotube/Nafion for sensitive
determination of paraquat.
AB - The screen-printed carbon electrode (SPCE) modified with various nanoparticles
has been studied for using as a working electrode in voltammetric technique. The
electrochemical behavior of paraquat on different electrodes was studied by
cyclic voltammetry (CV), and then differential pulse voltammetry (DPV) has been
employed for trace analysis of paraquat based on redox reaction which the peak
current was directly proportional to the concentration of paraquat in the
solution. The SPCE modified with carbon nanotube dispersed in Nafion and ethanol
(SPCE-CNT/Nafion) gave the best result. Sequential injection-differential pulse
voltammetric (SI-DPV) method has been developed for more automated analysis and
to reduce chemical consumption. The parameters affecting the SI-DPV system such
as step potential, modulation amplitude, flow rate, and concentration of sodium
chloride as an electrolyte were studied to improve the sensitivity. Under the
optimum condition of the system, i.e., Nafion concentration of 1% (w/v), volume
of CNT suspension of 2uL, flow rate of 100uLs-1, step potential of 5mV,
modulation amplitude of 100mV and concentration of sodium chloride of 1M, a
linear calibration graph in the range of 0.54-4.30uM with a good R2 of 0.9955 and
a limit of detection of 0.17uM (0.03mgL-1) were achieved. The proposed system
shows high tolerance to some possible interfering ions in natural water,
surfactant, and other pesticides. The relative standard deviation (RSD) was 4.2%
for 11 replicate measurements with the same electrode. The reproducibility for
the preparation of 7 modified electrodes was 2.3% RSD. Recoveries of the analysis
were obtained in the range of 82-106%. The developed system can be conveniently
applied for analysis without pretreatment of the samples.
PMID- 28501145
TI - A novel "turn-on" thiooxofluorescein-based colorimetric and fluorescent sensor
for Hg2+ and its application in living cells.
AB - A novel water-soluble fluorescent probe FLS2 based on the thiooxofluorescein
derivative has been firstly designed and synthesized. UV-vis absorption and
fluorescence spectra studies showed that the FLS2 as a colorimetric and
ratiometric fluorescent probe exhibited high selectivity and sensitivity towards
Hg2+, which was mainly attributed to the special binding with the receptor unit
accompanied with the spirolactam ring-opening progress. In addition, the probe
FLS2 could be used as a naked-eye indicator for Hg2+ with reversible response. It
displayed approximate 37-fold fluorescent enhancement at 529nm in the presence of
only 2.0 equiv. Hg2+ and the detection limit was calculated at about 39nM. What's
more, cellular imaging experiment revealed that the sensor had excellent
biocompatibility and low cytotoxicity that could be utilized for monitoring Hg2+
in living cells.
PMID- 28501146
TI - Selective solid phase extraction of chloroacetamide herbicides from environmental
water samples by amphiphilic magnetic molecularly imprinted polymers.
AB - In this study, a novel amphiphilic magnetic molecularly imprinted polymers
(MMIPs) have been prepared by using Fe3O4 microspheres as the magnetic core, 4
vinyl pyridine (4-VP) and alkenyl glycosides glucose (AGG) as functional co
monomers. Fe3O4 microspheres were directly encapsulated by the polymer without
any surface modification in the distillation-precipitation polymerization. The
morphology and composition of MMIPs were characterized by X-ray diffraction
(XRD), vibrating sample magnetometry (VSM), scanning electron microscopy (SEM),
and transmission electron microscopy (TEM). Binding property and magnetic
separation ability were systematically investigated through the equilibrium
binding experiments. The feasibility of magnetic molecular imprinted solid phase
extraction (MMISPE) was investigated for the selective enrichment of
chloroacetamide herbicides from environmental water samples. The developed MMISPE
HPLC method exhibited good linearity (0.1-200MUgL-1), low limit of detection
(0.03-0.06MUgL-1), and good precision (RSD<7%) under the optimized conditions.
The introduced MMISPE-HPLC method was successfully used to analyze
chloroacetamide herbicides in environmental water samples. Spiked chloroacetamide
herbicides recoveries in three water samples ranged from 82.1% to 102.9%. These
results indicated that amphiphilic MMIPs were the promising sorbents for the
selective enrichment of chloroacetamide herbicides at trace levels from real
environmental water samples.
PMID- 28501147
TI - A fluorescent homogeneous assay for myeloperoxidase measurement in biological
samples. A positive correlation between myeloperoxidase-generated HOCl level and
oxidative status in STZ-diabetic rats.
AB - Myeloperoxidase (MPO) is a key enzyme derived from leukocytes which is associated
with the initiation and progression of many inflammatory diseases. Increased
levels of MPO may contribute to cellular dysfunction and tissues injury by
producing highly reactive oxidants such as hypochlorous acid (HOCl).
Myeloperoxidase-generated HOCl is therefore considered as a relevant biomarker of
oxidative stress-related damage and its quantitation is of great importance to
the study of disease progression. In this context, the current study describes a
rapid, sensitive and homogeneous fluorescence-based method for detecting the MPO
chlorination activity in biological samples. This assay utilizes 7-hydroxy-2-oxo
2H-chromene-8-carbaldehyde oxime as a selective probe for HOCl detection, and is
adapted to 96-well microplates to allow high-throughput quantitation of active
MPO. The ability of the method to monitor HOCl release was further investigated
in hyperglycemic streptozotocin-treated diabetic rats. The data proved that the
present assay has a reliable performance when quantitating the active MPO in the
plasma of diabetic animals, a feature of inflammatory disease found concomitant
with an elevation of protein carbonyls levels and lipid peroxidation and which
was negatively correlated with the ratio of reduced-to-oxidized glutathione.
PMID- 28501148
TI - Simultaneous determination of acidic phytohormones in cucumbers and green bean
sprouts by ion-pair stir bar sorptive extraction-high performance liquid
chromatography.
AB - A simple, sensitive and inexpensive method of ion-pair stir bar sorptive
extraction (IP-SBSE) combined with high performance liquid chromatography
ultraviolet (HPLC-UV) detection was developed for the simultaneous determination
of three acidic phytohormones (salicylic acid (SA), indole-3-acetic acid (IAA),
and abscisic acid (ABA)) in vegetables. With the addition of cationic surfactant
cetyltrimethylammonium bromide (CTAB) in sample solutions, ion pair between CTAB
and target phytohormones were formed, leading to an improvement of the extraction
efficiency for target phytohormones by C18 silica coated SBSE. The factors
affecting the extraction efficiency of three target phytohormones by IP-C18
coated SBSE were optimized, and the optimal experimental conditions were
established. Under the optimal conditions, the limits of detection for SA, IAA
and ABA obtained by IP-C18-SBSE-HPLC-UV were 2.7, 2.1 and 0.3MUgL-1, with the
relative standard deviations of 6.0%, 5.0% and 8.3%, respectively, and the
enrichment factor was 32-49-fold. The developed method was applied to the
determination of SA, IAA and ABA in cucumbers and green bean sprouts, and the
recoveries of SA, IAA and ABA for the spiked samples were between 72.8% and
109.5%.
PMID- 28501149
TI - Novel cellulose-based halochromic test strips for naked-eye detection of alkaline
vapors and analytes.
AB - A simple, portable and highly sensitive naked-eye test strip is successfully
prepared for optical detection of gaseous and aqueous alkaline analytes. Novel pH
sensory tricyanofuran-hydrazone (TCFH) disperse colorant containing a hydrazone
recognition functional moiety is successfully synthesized via azo-coupling
reaction between active methyl-containing tricyanofuran (TCF) heterocycle and
diazonium salt of 4-aminobenzaldehyde followed by Knoevenagel condensation with
malononitrile. UV-vis absorption spectra display solvatochromism and reversible
color changes of the TCFH solution in dimethyl sulfoxide in response to pH
variations. We investigate the preparation of hydrophobic cellulose/polyethylene
terephthalate composites characterized by their high affinity for disperse dyes.
Composite films made from CA, Cell/CA, PET/CA, and Cell/PET-CA are produced via
solvent-casting procedure using 10-30% modified cellulose or modified
polyethylene terephthalate. The mechanical properties and morphologies of these
composite films are investigated. The prepared pH-sensory hydrazone-based
disperse dye is then applied to dye the produced cellulose-based composite films
employing the high temperature pressure dyeing procedure. The produced
halochromic PET-CA-TCFH test strip provide an instant visible signal from orange
to purple upon exposure to alkaline conditions as proved by the coloration
measurements. The sensor strip exhibits high sensitivity and quick detection
toward ammonia in both of aqueous and vapor phases by naked-eye observations at
room temperature and atmospheric pressure.
PMID- 28501150
TI - Facile one-pot fabrication of Ag@MOF(Ag) nanocomposites for highly selective
detection of 2,4,6-trinitrophenol in aqueous phase.
AB - Ag@MOF(Ag) nano-composites were fabricated through one-pot facile reflux reaction
from the raw materials of AgNO3 and 2-aminoterephthalic acid, and were then
characterized through SEM, TEM, XRD, XPS, and FTIR, which showed a high
fluorescence quantum yield (10.6%) and exhibited outstanding selectivity and
excellent sensitivity for 2,4,6-trinitrophenol (TNP) over a concentration range
of 1-29MUM in water. The fluorescence quenching mechanism may be attributed to
hydrogen-bonding interactions and resonance energy transfer.
PMID- 28501151
TI - Micro-sampling method based on high-resolution continuum source graphite furnace
atomic absorption spectrometry for calcium determination in blood and
mitochondrial suspensions.
AB - A micro-sampling and straightforward method based on high resolution continuum
source atomic absorption spectrometry (HR-CS AAS) was developed to determine
extracellular and intracellular Ca in samples of interest in clinical and
biomedical analysis. Solid sampling platforms were used to introduce the micro
samples into the graphite furnace atomizer. The secondary absorption line for Ca,
located at 239.856nm, was selected to carry out the measurements. Experimental
parameters such as pyrolysis and atomization temperatures and the amount of
sample introduced for the measurements were optimized. Calibration was performed
using aqueous standards and the approach to measure at the wings of the
absorption lines was employed for the expansion of the linear response range. The
limit of detection was of 0.02mgL-1 Ca (0.39ng Ca) and the upper limit of linear
range was increased up to 8.0mgL-1 Ca (160ng Ca). The proposed method was used to
determine Ca in mitochondrial suspensions and whole blood samples with successful
results. Adequate recoveries (within 91-107%) were obtained in the tests
performed for validation purposes.
PMID- 28501153
TI - Faradaic and capacitive current estimation by means of Independent Components
Analysis and 1kHz sampling.
AB - In this work it was demonstrated for the first time that Independent Components
Analysis non-deterministic multivariate strategy enables estimation of the
Faradic and double layer charging current components in differential pulse and
anodic stripping voltammetry. The signals separation can be realized based on the
different shapes of the capacitive and Faradaic current functions. The set of
calibration voltammograms measured with the 1kHz sampling frequency is the
sufficient data to retrieve signals compatible with the theoretical shapes, with
r2 greater than 0.987 for Faradaic component and greater than 0.994 for
capacitive component. In the effect, DP voltammograms of Pb(II) and Cd(II)
recorded on silver annular band electrode were constructed using only Faradaic
component. Quantitative analysis was performed and calibration models were
calculated by different waiting time and sampling time, what demonstrated the
possibility of significant improvement of sensitivity in considered experiments.
PMID- 28501152
TI - Determination of inorganic arsenic in algae using bromine halogenation and on
line nonpolar solid phase extraction followed by hydride generation atomic
fluorescence spectrometry.
AB - Accurate, stable and fast analysis of toxic inorganic arsenic (iAs) in
complicated and arsenosugar-rich algae matrix is always a challenge. Herein, a
novel analytical method for iAs in algae was reported, using bromine halogenation
and on-line nonpolar solid phase extraction (SPE) followed by hydride generation
atomic fluorescence spectrometry (HG-AFS). The separation of iAs from algae was
first performed by nonpolar SPE sorbent using Br- for arsenic halogenation. Algae
samples were extracted with 1% perchloric acid. Then, 1.5mL extract was reduced
by 1% thiourea, and simultaneously reacted (for 30min) with 50MUL of 10% KBr for
converting iAs to AsBr3 after adding 3.5mL of 70% HCl to 5mL. A polystyrene (PS)
resin cartridge was employed to retain arsenicals, which were hydrolyzed, eluted
from the PS resin with H2O, and categorized as iAs. The total iAs was quantified
by HG-AFS. Under optimum conditions, the spiked recoveries of iAs in real algae
samples were in the 82-96% range, and the method achieved a desirable limit of
detection of 3MUgkg-1. The inter-day relative standard deviations were 4.5% and
4.1% for spiked 100 and 500MUgkg-1 respectively, which proved acceptable for this
method. For real algae samples analysis, the highest presence of iAs was found in
sargassum fusiforme, followed by kelp, seaweed and laver.
PMID- 28501154
TI - New approach to H-point standard addition method for detection and elimination of
unspecific interferences in samples with unknown matrix.
AB - A novel method for correction of unknown unspecific (additive) interferences was
developed in sequential injection analysis (SIA) using a Lab on Valve module
(LOV) with spectrophotometric detection. The method implements a novel idea to
calibrate by the standard addition method in several different chemical
conditions created in such a way to measure different signal for an analyte and
unchanged signal for interferents causing additive effect. This approach, being
an enhancement of the H-point standard addition method (HPSAM), enables to
quantify unbiased concentration of an analyte in the presence of unknown
interferences. The method was tested on the example of the determination of
ascorbic acid in soft drinks and juices basing on reduction of Fe(III) to Fe(II)
and reaction of the latter with o-phenanthroline to the ferroin complex absorbing
at 512.0nm. The analytical utility of the method has been verified and confirmed
by the spectrophotometric determination of total acidity in rose and red wines in
the presence of bromothymol blue absorbing at 616.0nm. Calibration solutions were
prepared automatically in the designed flow system. Ascorbic acid was determined
with LOD of 1.4mgL-1 and LOQ of 4.2mgL-1 within linear working range up to 80mgL
1, while in case of the determination of total acidity the values of 4.2, 11.8
and 100, respectively, were obtained. A sample was consumed in volumes of 400 and
1000uL in both cases. The analyses are simple, "green", and non-expensive. The
developed method is readily applicable to analysis of real samples of complex
unknown matrices and adaptable to different analytical methods.
PMID- 28501155
TI - Morphology-tunable polydopamine nanoparticles and their application in Fe3+
detection.
AB - In this work, we discovered the morphology transformation property of
polydopamine (PDA) nanomaterials, the addition of Fe3+ initiated the dramatic
morphology transformation of PDA dots from aggregated plate-like to uniform
willow-leaf-like morphology. Further study revealed that this fascinating
morphology transformation process could be attributed to the oxidative nature and
coordination characteristic of Fe3+. This is the first report on the morphology
transformation ability of PDA, and a probable self-assembled mechanism was
proposed to explain this issue. Besides, we noticed that morphological and
fluorescent properties of PDA dots were closely related, thus a fluorescent Fe3+
detection method was presented based on the morphology-tunable PDA dots. With the
proposed method, selective Fe3+ detection was achieved with a wide linear dynamic
range of 10MUM to 1mM. Furthermore, since the morphology tuning behavior of PDA
dots was easy to operate, we anticipate this ability will find significant
utility in sensing, drug delivery, and tissue engineering.
PMID- 28501156
TI - Broadcasting photonic lab on a chip concept through a low cost manufacturing
approach.
AB - A low cost fabrication process for photonic lab on a chip systems is here
proposed. For the implementation of the masters suitable for cast molding
fabrication, an inexpensive dry film photoresist, patternable using standard
laboratory equipment, is benchmarked against standardized SU-8 masters obtained
using UV lithography and systems manufacture in clean room facilities. Results
show adequate system fabrication and a comparable performance of the photonic
structures for absorbance/extinction measurements.
PMID- 28501157
TI - pH-Triggered Disaggregation-Induced Emission (DIE) probe for sensoring minor-pH
changes in near infrared fluorescence region.
AB - A new strategy for pH-responsive near infrared (NIR) cyanine dye, based on the
concept of triggered disaggregation-induced emission (DIE), has been developed.
Schiff base group was introduced to the molecular scaffold of Cy7, and promoted
the aggregation of cyanine in pH7.4 buffer due to the strong pi-pi interaction.
While in an acidic (pH 5.8) environment, the Schiff base group was hydrolyzed by
acid and the nanoparticles were disaggregated. The vanishing of the
intermolecular aggregation-caused quenching thus induced a fluorescence recovery
of 96 folds. Moreover, abundant kinds of Schiff base provide more potential
cyanine dyes for pH-responsive ultrahigh NIR fluorescence "Off/On" ratio, which
could work as the intelligent bio-imaging probes in near future.
PMID- 28501158
TI - Poly(vinyl alcohol) capped silver nanoparticles for antioxidant assay based on
seed-mediated nanoparticle growth.
AB - A simple and rapid method for measurement of total antioxidant capacity (TAC) was
developed. In this work, gallic acid was used as the antioxidant standard.
Poly(vinyl alcohol) embedded silver nanoparticles (PVA-AgNPs) were employed as a
colorimetric sensor. The detection principle was based on the seed-mediated
nanoparticle growth technique. The PVA-AgNPs act as a catalyst in the reduction
of Ag+ by gallic acid by providing nucleation seeds. Ag+ was reduced to Ag
degrees and accumulated on the PVA-AgNP surface, leading to an increase in the
size of particles. The absorbance of the colloidal solution was drastically
enhanced with a small red shift. Under optimal conditions, a linear response was
established between the change in absorbance and the TAC value expressed in terms
of gallic acid equivalents. The linear range was from 25 to 200MUM with a
detection limit of 22.1MUM. Satisfactory precision was obtained with % relative
standard deviation (RSD) of 2.17. The developed sensor was successfully applied
for TAC assessment of commercial ginger products. The PVA-AgNP sensor offers
rapid analysis (within 5min) compared to other nanoparticle-based antioxidant
assays. Synthesis of the particles and assay involved less-toxic chemicals, and
is therefore a "greener" method.
PMID- 28501159
TI - Depleting high-abundant and enriching low-abundant proteins in human serum: An
evaluation of sample preparation methods using magnetic nanoparticle, chemical
depletion and immunoaffinity techniques.
AB - The efficiency of three different depletion methods to remove the most abundant
proteins, enriching those human serum proteins with low abundance is checked to
make more efficient the search and discovery of biomarkers. These methods utilize
magnetic nanoparticles (MNPs), chemical reagents (sequential application of
dithiothreitol and acetonitrile, DTT/ACN), and commercial apparatus based on
immunoaffinity (ProteoMiner, PM). The comparison between methods shows
significant removal of abundant protein, remaining in the supernatant at
concentrations of 4.6+/-0.2, 3.6+/-0.1, and 3.3+/-0.2uguL-1 (n=3) for MNPs,
DTT/ACN and PM respectively, from a total protein content of 54uguL-1. Using GeLC
MS/MS analysis, MNPs depletion shows good efficiency in removing high molecular
weight proteins (>80kDa). Due to the synergic effect between the reagents DTT and
ACN, DTT/ACN-based depletion offers good performance in the depletion of thiol
rich proteins, such as albumin and transferrin (DTT action), as well as of high
molecular weight proteins (ACN action). Furthermore, PM equalization confirms its
efficiency in concentrating low-abundant proteins, decreasing the dynamic range
of protein levels in human serum. Direct comparison between the treatments
reveals 72 proteins identified when using MNP depletion (43 of them exclusively
by this method), but only 20 proteins using DTT/ACN (seven exclusively by this
method). Additionally, after PM treatment 30 proteins were identified, seven
exclusively by this method. Thus, MNPs and DTT/ACN depletion can be simple,
quick, cheap, and robust alternatives for immunochemistry-based protein
depletion, providing a potential strategy in the search for disease biomarkers.
PMID- 28501160
TI - Bioaffinity-based assay for the sensitive detection and discrimination of sweat
aimed at forensic applications.
AB - Sweat is a well-known piece of biological evidence that is actually used much
less than expected. Biological samples are important because their components can
often provide some type of information about a person-of-interest. Sweat, in
particular, is important because of its DNA content which can be extracted and
analyzed to provide information that can be imperative to a criminal
investigation. While it is a very important source of forensic information, the
methods for detection and discrimination of sweat are limited, causing it to be
overlooked during evidence collection. This manuscript presents a biocatalytic
method for sweat detection that utilizes an enzyme cascade system that has the
capability to detect trace amounts of sweat and distinguish it from saliva, even
after the sample has dried. The results show the initial calibration studies
performed to insure that the cascade performs well using both mimicked and
authentic sweat samples which have components that could negatively affect the
enzymes needed for the analysis. The method presented here also has the potential
to be adapted for on-site analysis. The initial results of the development of a
sweat-sensitive strip are shown here.
PMID- 28501162
TI - Solidification of floating organic droplet in dispersive liquid-liquid
microextraction as a green analytical tool.
AB - Dispersive liquid-liquid microextraction (DLLME) is a special type of
microextraction in which a mixture of two solvents (an extracting solvent and a
disperser) is injected into the sample. The extraction solvent is then dispersed
as fine droplets in the cloudy sample through manual or mechanical agitation.
Hence, the sample is centrifuged to break the formed emulsion and the extracting
solvent is manually separated. The organic solvents commonly used in DLLME are
halogenated hydrocarbons that are highly toxic. These solvents are heavier than
water, so they sink to the bottom of the centrifugation tube which makes the
separation step difficult. By using solvents of low density, the organic
extractant floats on the sample surface. If the selected solvent such as
undecanol has a freezing point in the range 10-25 degrees C, the floating droplet
can be solidified using a simple ice-bath, and then transferred out of the sample
matrix; this step is known as solidification of floating organic droplet (SFOD).
Coupling DLLME to SFOD combines the advantages of both approaches together. The
DLLME-SFOD process is controlled by the same variables of conventional liquid
liquid extraction. The organic solvents used as extractants in DLLME-SFOD must be
immiscible with water, of lower density, low volatility, high partition
coefficient and low melting and freezing points. The extraction efficiency of
DLLME-SFOD is affected by types and volumes of organic extractant and disperser,
salt addition, pH, temperature, stirring rate and extraction time. This review
discusses the principle, optimization variables, advantages and disadvantages and
some selected applications of DLLME-SFOD in water, food and biomedical analysis.
PMID- 28501161
TI - Fabrication of selective chemical sensor with ternary ZnO/SnO2/Yb2O3
nanoparticles.
AB - Construction of highly efficient toxic chemical sensors is the key approach for
the determination of carcinogenic chemicals in the environment and ecosystem. We
report here, an efficient acetone chemical sensor based on the analytical
performances such as sensitivity, lower-detection limit, reproducibility, and
good linearity. The proposed acetone-detecting electrode was introduced by the
implementation of ZnO/SnO2/Yb2O3 nanoparticles (NPs) as a successful electron
mediator with glassy carbon electrode (GCE) assembly. The prepared NPs of
ZnO/SnO2/Yb2O3 were well crystalline-doped nanomaterial and produced by
implementation of hydrothermal procedure at low temperature. The conventional
methods such as Fourier-transform infrared spectroscopy (FTIR), ultraviolet
visible spectroscopy (UV/vis), field emission scanning electron microscopy
(FESEM), X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray
spectroscopy (EDS), and powder x-ray diffraction (XRD) were utilized for
characterization of prepared NPs in terms of morphological, elemental, optical
and structural properties. The large linear dynamic range (LDR) of 0.34nmolL-1 to
3.4mmolL-1 with lower detection limit (S/N=3) of 0.05+/-0.002nmolL-1 and a higher
sensitivity of 17.09uAmmolL-1cm-2 were exhibited by lab-made fabricated sensor
based on ZnO/SnO2/Yb2O3 NPs for selective acetone detection. In shortly, the
ZnO/SnO2/Yb2O3 NPs are utilized as an excellent electron mediator with Nafion/GCE
assembly in a chemical sensor for acetone detection even at the very low
concentration. Therefore, the chemical sensor is fabricated with ZnO/SnO2/Yb2O3
NPs may be a promising highly sensitive sensor by reliable I-V detection method
for the effective detection of hazardous and carcinogenic chemicals in medical as
well as health-care fields.
PMID- 28501163
TI - On-line immunoaffinity solid-phase extraction capillary electrophoresis mass
spectrometry using Fab'antibody fragments for the analysis of serum
transthyretin.
AB - This paper describes an on-line immunoaffinity solid-phase extraction capillary
electrophoresis mass spectrometry (IA-SPE-CE-MS) method using an immunoaffinity
sorbent with Fab' antibody fragments (Fab'-IA) for the analysis of serum
transthyretin (TTR), a homotetrameric protein (Mr~56,000) involved in different
types of amyloidosis. The IA sorbent was prepared by covalent attachment of Fab'
fragments obtained from a polyclonal IgG antibody against TTR to succinimidyl
silica particles. The Fab'-IA-SPE-CE-MS methodology was first established
analyzing TTR standard solutions. Under optimized conditions, repeatability and
reproducibility were acceptable, the method was linear between 1 and 25ugmL-1,
limits of detection (LODs) were around 0.5ugmL-1 (50-fold lower than by CE-MS,
~25ugmL-1) and different TTR conformations were observed (folded and unfolded).
The applicability of the developed method to screen for familial amyloidotic
polyneuropathy type I (FAP-I), which is the most common hereditary systemic
amyloidosis, was evaluated analyzing serum samples from healthy controls and FAP
I patients. For the analysis of sera, the most abundant proteins were
precipitated with 5% (v/v) of phenol before Fab'-IA-SPE-CE-MS. The current method
enhanced our previous results for the analysis of TTR using intact antibodies
immobilized on magnetic beads. It allowed a slight improvement on LODs (2-fold),
the detection of proteoforms found at lower concentrations and the preparation of
microcartridges with extended durability.
PMID- 28501164
TI - A nanocluster-based fluorescent sensor for sensitive hemoglobin detection.
AB - In this report, a fluorescence sensor for sensitive detection of hemoglobin was
developed. Gold nanoclusters were first synthesized with bovine serum albumin. It
was found that both hydrogen peroxide and hemoglobin could weakly quench the
fluorescence from the gold nanoclusters, but when these two were applied onto the
nanolcusters simultaneously, a much improved quenching was resulted. This
enhancing effect was proved to come from the catalytic generation of hydroxyl
radical by hemoglobin. Under an optimized condition, the quenching linearly
related to the concentration of hemoglobin in the range of 1-250nM, and a limit
of detection as low as 0.36nM could be obtained. This provided a sensitive means
for the quantification of Hb. The sensor was then successfully applied for blood
analyses with simple sample pretreatment.
PMID- 28501165
TI - A portable somatic cell counter based on a multi-functional counting chamber and
a miniaturized fluorescence microscope.
AB - A somatic cell count is the concentration or density of somatic cells in milk,
and is an important indicator for monitoring mastitis incidence and milk quality
in the dairy industry. Managing and controlling mastitis based on somatic cell
counts can help ensure high milk quality and yield. A major challenge when
translating existing cell counting methods to such application is that they
require off-chip sample preparation and complicated sample and reagent delivery
steps that cannot be easily performed in resource-limited settings such as dairy
farms. Here, we describe an integrated cell counting platform that enables
automatic sample delivery into a cell counting chamber and on-chip sample
preparation without requiring any off-chip processes, and that simultaneously
provides a miniaturized, hand-held fluorescence device for the identification of
fluorescently-labelled somatic cells. Our platform thus allows simple, rapid and
accurate enumeration of somatic cells in milk. We successfully demonstrated its
capability of counting somatic cells in milk, which can be easily performed even
by non-experts without additional instrumentation. The platform represents a
promising tool for everyday milk-quality tracking and for controlling mastitis
occurrence.
PMID- 28501166
TI - Synthesis and evaluation of a molecularly imprinted polymer for selective
adsorption and quantification of Acid Green 16 textile dye in water samples.
AB - An alternative for determining environmental pollutants, like textile dyes, is
the use of molecularly imprinted polymers (MIPs) as solid phase extraction (SPE)
or as sensor recognition systems. MIPs are tailor-made artificial receptor sites
in a polymer, which present good affinity and selectivity. This work shows the
synthesis of MIPs for the Acid Green 16 (AG16) textile dye and the results of
rebinding, selectivity and application of this MIP in water samples. MIP
synthesis was performed using AG16 dye (template), 1-vinylimidazole (functional
monomer), ethylene-glycol-dimethacrylate (cross-link), 2,2'-azobis(2
methylpropionitrile) (initiator) and methanol (solvent) by bulk synthesis. The
imprinted polymer presented excellent rebinding of 83%, an imprinted factor of
6.91 and great selectivity in comparison with other textile dyes. Additionally,
the MIP showed high efficiency in the extraction of this dye in water samples,
presenting a recovery rate close to 100% and a better performance when compared
to commercial SPE cartridges. Due to this excellent performance for AG16, the
application of this MIP to determine dyes in different matrices of environmental
importance is promising.
PMID- 28501167
TI - Polyoxometalate incorporated polymer monolith microextraction for highly
selective extraction of antidepressants in undiluted urine.
AB - In this work, a polyoxometalate (POM) incorporated polymer monolith
microextraction (PMME) was successfully proposed and employed in the selective
extraction of basic antidepressants in undiluted urine sample. This hybrid
monolith exhibited strong cation-exchange interaction (SCX) with positively
charged antidepressants when pH was 3.0, because of the multiple ionizable
moieties on polyanionic POM. As such, antidepressants in complex sample matrices
were efficiently extracted by the monolith, and the matrix effect was
significantly reduced. In addition, due to the high amount of anionic POM, the
monolith exhibited remarkable extraction capacities for target antidepressants
ranging from 4.7 to 5.8mg/g. Further, the POM incorporated PMME was coupled with
high-performance liquid chromatography-ultraviolet (HPLC-UV). Thus,
antidepressants in undiluted urine sample was efficiently extracted under
optimized extraction conditions online. The limits of detection (LODs) for the
target antidepressants ranged from 0.7 to 1.4ng/mL, and the linear range was 5
1000ng/mL with determination coefficients (R2) higher than 0.9960. The recoveries
ranged from 86.8% to 104.0% with relative standard deviations (RSDs) of 0.4
10.1%. The proposed procedure was successfully applied to determine
antidepressant in human urine. Taken together, the developed method presented a
new strategy for the analysis of basic drugs in undiluted urine sample, which
could be used for monitoring medicines in pharmacokinetic analysis.
PMID- 28501168
TI - High sensitivity thermal lens microscopy: Cr-VI trace detection in water.
AB - In this work, a low detection limit for hexavalent chromium in water of parts per
trillions (21ng/L) was achieved using a micro-spatial thermal lens spectroscopy
setup with coaxial counter-propagating pump and probe laser beams and an
integrated passive optical Fabry-Perot resonator, aided with a well-established
diphenyl carbazide colorimetric method. Cr-VI concentrations in the range of
MUg/L, i.e. well-below the toxicity thresholds in humans and animals (26 and
190mg/L respectively) and below those delimited by international regulations for
drink water (~0.05-0.5mg/L), have been obtained by measurements in bottled and
tap water samples. The developed thermal lens microscope is also capable to
detect Cr-VI directly in potassium dichromate solutions using pump beam
wavelengths within the very low optical absorption region in the visible part of
the spectrum, i.e., without the use of any colorimetric method.
PMID- 28501169
TI - Aqueous biphasic systems containing PEG-based deep eutectic solvents for high
performance partitioning of RNA.
AB - In this work, 16 kinds of novel deep eutectic solvents (DESs) composed of
polyethylene glycol (PEG) and quaternary ammonium salts, were coupled with
Aqueous Biphasic Systems (ABSs) to extract RNA. The phase forming ability of ABSs
were comprehensively evaluated, involving the effects of various proportions of
DESs' components, carbon chain length and anions species of quaternary ammonium
salts, average molecular weights of PEG and inorganic salts nature. Then the
systems were applied in RNA extraction, and the results revealed that the
extraction efficiency values were distinctly enhanced by relatively lower PEG
content in DESs, smaller PEG molecular weights, longer carbon chain of quaternary
ammonium salts and more hydrophobic inorganic salts. Then the systems composed of
[TBAB][PEG600] and Na2SO4 were utilized in the influence factor experiments,
proving that the electrostatic interaction was the dominant force for RNA
extraction. Therefore, back-extraction efficiency values ranging between 85.19%
and 90.78% were obtained by adjusting the ionic strength. Besides, the selective
separation of RNA and tryptophane (Trp) was successfully accomplished. It was
found that 86.19% RNA was distributed in the bottom phase, while 72.02% Trp was
enriched in the top phase in the novel ABSs. Finally, dynamic light scattering
(DLS) and transmission electron microscope (TEM) were used to further investigate
the extraction mechanism. The proposed method reveals the outstanding feasibility
of the newly developed ABSs formed by PEG-based DESs and inorganic salts for the
green extraction of RNA.
PMID- 28501170
TI - A star-shaped poly(2-methyl-2-oxazoline)-based antifouling coating: Application
in investigation of the interaction between acetaminophen and bovine serum
albumin by frontal analysis capillary electrophoresis.
AB - In this work, an antifouling capillary modified with star-shaped poly(2-methyl-2
oxazoline)-based copolymer was used to study the interaction between
acetaminophen (APAP) and bovine serum albumin (BSA) by frontal analysis capillary
electrophoresis (FACE). The star-shaped copolymer, poly(ethylene imine)-graft
poly(2-methyl-2-oxazoline) (PEI-g-PMOXA), was immobilized onto the fused-silica
capillary inner wall via dopamine-assisted co-deposition strategy, yielding a PEI
g-PMOXA/polydopamine (PDA)-coated antifouling capillary, i.e., an antifouling
capillary coated with the PEI-g-PMOXA/PDA co-deposited film. Electroosmotic flow
(EOF) mobility of the PEI-g-PMOXA/PDA-coated capillary was almost zero in a wide
pH range (3.0-10.0), while the EOF mobility of bare capillary was much larger and
increased significantly with pH increasing. When the PEI-g-PMOXA/PDA-coated
capillary was exploited to separate a protein mixture including cytochrome c,
lysozyme, ribonuclease A and alpha-chymotrypsinogen A, the theoretical plate
numbers were of five orders of magnitude which were about ten-fold higher over
those obtained with bare capillary; in addition, the RSD values of migration time
were mostly less than 0.7% (30 consecutive runs) which were much smaller than
those of bare capillary (c.a. 5.7%). The protein-resistant PEI-g-PMOXA/PDA-coated
capillary was then used to investigate the interaction between APAP and BSA by
FACE, the binding constant and number of binding sites at 25 degrees C and pH 7.4
(Tris/HCl buffer of 25mM) were 1.39*104M-1 and 1.08, respectively, which were
comparable to the results determined by fluorescence spectroscopic measurement
(3.18*104M-1 and 1.19, respectively).
PMID- 28501171
TI - A novel magnetic/photoluminescence bifunctional nanohybrid for the determination
of trypsin.
AB - In this work, we have designed a novel kind of nanohybrid with magnetic and
photoluminescence (PL) property for trypsin detection. The modified magnetic
Fe3O4 nanoparticles (MNPs) with polydopamine (PDA) and human serum albumin (HSA)
were prepared through a one step self-polymerization under mild condition. The
polydopamine (PDA) coating on MNPs can improve the biocompatibility of the MNP
PDA-HAS composite due to its hydrophilicity and multifunctional groups. When MNP
PDA-HSA composite was added into the Anti-HSA modified CdTe QDs (anti-HSA-QDs),
HSA on the MNP-PDA-HSA composite was captured by the site of anti-HSA-QDs to form
MNP-PDA-HSA/anti-HSA-QDs nanohybrid. Therefore, the photoluminescence of QDs can
be quenched by Fe3O4 nanoparticles due to the electron transfer. In the presence
of trypsin, the protein (anti-HSA) was digested by trypsin and QDs was separated
from the nanohybrid surface. As a result, the photoluminescence intensity of QDs
was recovered. The magnetic/luminescent bifunctional nanohybrid displayed
excellent analytical performance for the detection of trypsin in the range of 0.5
30MUg/mL with a low detection limit of 0.25MUg/mL.
PMID- 28501172
TI - Combining phagomagnetic separation with immunoassay for specific, fast and
sensitive detection of Staphylococcus aureus.
AB - A Staphylococcus aureus (S. aureus)-specific lytic bacteriophage P-S. aureus-9,
isolated from an environmental water sample, was assembled on magnetic beads for
capturing S. aureus from samples through magnetic separation. Horseradish
Peroxidase (HRP) labeled immunoglobulin (IgG) antibodies were used to detect the
captured S. aureus by reacting with protein A on S. aureus followed by
colorimetric signals, which were generated from the catalytic reaction between
HRP and the substrate 3,3',5,5'-Tetramethylbenzidine (TMB). Under optimal
conditions, the calibration curve was linear from 1.0*104 to 1.0*106CFUmL-1. The
limit of detection (LOD) for the assay was 2.47*103CFUmL-1 and 8.86*103CFUmL-1 of
S. aureus in PBS and apple juice, respectively. Moreover, the whole assay
revealed outstanding specificity towards S. aureus, without any interference of
common pathogenic bacteria, and can be completed within 90min without any pre
enrichment. As far as known, it was the first time to detect S. aureus based on
the double site recognition of bacteriophage and mammal IgG. The novel approach
has shown good potentials for a rapid, specific, cheap and simple detection of S.
aureus in food samples.
PMID- 28501173
TI - An exploiting of cost-effective direct current conductivity detector in gas
diffusion flow injection system.
AB - In this work, a homemade direct current (DC) conductivity detector as an
alternative cost-effective detection device has been fabricated and investigated
to use in flow analysis system. Under the selected appropriate conditions of flow
system, the electrolysis of a carrier stream at the conductivity detector was
negligible and provides well-defined signal. The cost-effective DC conductivity
detector was demonstrated to couple with gas diffusion flow injection system for
determination of dissolved inorganic carbon (DIC) in water. The method is based
on the conversion of DIC (dissolved CO2, HCO3- and CO32-) presented in the
injected sample to carbon dioxide in an acidic donor stream and then CO2 gas
diffuses through a hydrophobic porous membrane to an acceptor stream. As a
result, the change of conductivity signal was observed corresponding to DIC
concentration. A linear calibration range of DIC in 1.0-10mmolL-1, with limit of
detection of 70umolL-1, repeatability of <3% RSD and 15 injections h-1 sample
throughput can be obtained. This method was applied for DIC determination in
natural water.
PMID- 28501174
TI - Polyhydric polymer-functionalized fluorescent probe with enhanced aqueous
solubility and specific ion recognition: A test strips-based fluorimetric
strategy for the rapid and visual detection of Fe3+ ions.
AB - A polyhydric polymer-functionalized probe with enhanced aqueous solubility was
designed initially by coupling 1-pyrenecarboxyaldehyde (Pyr) onto poly(vinyl
alcohol) (PVA) via the one-step condensation reaction. Polyhydric PVA polymer
chains could facilitate the Pyr fluorophore with largely improved aqueous
solubility and especially strong cyan fluorescence. Importantly, the fluorescence
of the PVA-Pyr probes could thereby be quenched specifically by Fe3+ ions through
the strong PVA-Fe3+ interaction triggering the polymeric probe aggregation.
Furthermore, a test strips-based fluorimetric method was developed with the
stable and uniform probe distribution by taking advantage of the unique film
forming ability and the depression capacity of "coffee-stain" effects of PVA
matrix. The as-developed test strips could allow for the rapid and visual
detections of Fe3+ ions simply by a dipping way, showing a linear concentration
range of 5.00-300MUM, with the detection limit of 0.73MUM. Moreover, the proposed
method was applied to the evaluation of Fe3+ ions in natural water samples,
showing the analysis performances better or comparable to those of current
detection techniques. This test strips-based fluorimetric strategy promises the
extensive applications for the rapid on-site monitoring of Fe3+ ions in
environmental water and the outdoor finding of the potential iron mines.
PMID- 28501175
TI - Sensitive determination of endogenous hydroxyl radical in live cell by a BODIPY
based fluorescent probe.
AB - The sensitive and selective fluorescence probe for hydroxyl radical analysis is
of significance because hydroxyl radical plays key roles in many physiological
and pathological processes. In this work, a novel organic fluorescence molecular
probe OHP for hydroxyl radical is synthesized by a two-step route. The probe
employs 4-bora-3a,4a-diaza-s-indacene (difluoroboron dipyrromethene, BODIPY) as
the fluorophore and possesses relatively high fluorescence quantum yields
(77.14%). Hydroxyl radical can rapidly react with the probe and quench the
fluorescence in a good linear relationship (R2=0.9967). The limit of detection is
determined to be as low as 11nM. In addition, it has been demonstrated that the
probe has a good stability against pH and light illumination, low cytotoxicity
and high biocompatibility. Cell culture experimental results show that the probe
OHP is sensitive and selective for imaging and tracking endogenous hydroxyl
radical in live cells.
PMID- 28501176
TI - Liquid chromatography-high resolution mass spectrometric methods for the
surveillance monitoring of cyanotoxins in freshwaters.
AB - A comprehensive risk management on human exposure to cyanotoxins, whose
production is actually unpredictable, is limited by reliable analytical tools for
monitoring as many toxic algal metabolites as possible. Two analytical approaches
based on a LC-QTOF system for target analysis and suspect screening of
cyanotoxins in freshwater were presented. A database with 369 compounds belonging
to cyanobacterial metabolites was developed and used for a retrospective data
analysis based on high resolution mass spectrometry (HRMS). HRMS fragmentation of
the suspect cyanotoxin precursor ions was subsequently performed for correctly
identifying the specific variants. Alternatively, an automatic tandem HRMS
analysis tailored for cyanotoxins was performed in a single chromatographic run,
using the developed database as a preferred precursor ions list. Twenty-five
extracts of surface and drinking waters contaminated by cyanobacteria were
processed. The identification of seven uncommon microcystins (M(O)R, MC-FR, MSer7
YR, D-Asp3MSer7-LR, MSer7-LR, dmAdda-LR and dmAdda-YR) and 6 anabaenopeptins (A,
B, F, MM850, MM864, oscyllamide Y) was reported. Several isobaric variants, fully
separated by chromatography, were pointed out. The developed methods are proposed
to be used by environmental and health agencies for strengthening the
surveillance monitoring of cyanotoxins in water.
PMID- 28501177
TI - Determination of stability characteristics for electrochemical biosensors via
thermally accelerated ageing.
AB - Biosensors are devices that are prone to ageing; this phenomenon can be
characterized as a decrease in signal over time. Biosensor stability is of a
crucial importance for commercial success and as biosensors are presently being
applied to an increasing and variety of applications. Stability characteristics
related to shelf life, reusability and/or continuous use stability are often
poorly investigated or unreported in literature, yet are important factors.
Instability or ageing can be accelerated at an elevated temperature; Arrhenius
(exponential) and linear models were investigated in order to propose a novel
method for rapid ageing characteristics determination. Linear correlation proved
more suitable with higher coefficients of determination than exponential
correlation. Degradation rate is linearly dependent on temperature and by
utilizing the proposed models, long term shelf life of a biosensor can be
determined in 4 days and continuous use stability in less than 24h. Reusability
studies are found to correlate poorly due to the unpredictable nature of
biosensor handling. Basic constructed screen printed electrode glucose oxidase
biosensors were used as a model biosensor in order to propose models for shelf
life, reusability and continuous use stability.
PMID- 28501178
TI - Electrochemically deposited conductive composite sorbent for highly efficient
online solid-phase microextraction of jasmonates in plant samples.
AB - Conductive composite films composed of poly (3, 4-ethylenedioxythiophene) (PEDOT)
and sulfonated graphene were electrochemically deposited on carbon fiber bundle
in aqueous solutions for solid phase microextraction (SPME). During the electro
polymerization process, negatively charged sulfonated graphene were doped in
PEDOT layer and uniformly dispersed in the composite. The modified carbon fiber
bundle worked as sorbent was then successfully applied to online SPME-HPLC-UV
analysis of jasmonates in wintersweet flowers. High extraction efficiency (over
420-fold), low limits of detection (0.1ngmL-1 for jasmonic acid and 0.01ngmL-1
for methyl jasmonate) and wide linear ranges (0.5-5000 and 0.05-5000ngmL-1,
R>0.9997) have been obtained. It has been demonstrated that this method can be
well used for jasmonates analysis in fresh wintersweet flowers with good
recoveries (92.4-98.9%). The results were confirmed by HPLC-MS method.
PMID- 28501179
TI - Determination of veterinary penicillin antibiotics by fast high-resolution liquid
chromatography and luminescence detection.
AB - A chromatographic method based on the use of a fused-core column and luminescence
detection is described for the determination of six penicillin antibiotics used
in veterinary practice, namely amoxicillin, ampicillin, penicillin G, oxacillin,
cloxacillin and nafcillin. The use of this column provides the separation of
these antibiotics with retention times lower than 4.5min. The tris(2,2'
bipyridyl)ruthenium(II) [Ru(bpy)32+] - Ce(IV) system has been used as post-column
derivatization reagent, obtaining a luminescence signal (lambdaem 610nm)
proportional to the analyte concentration when the system is excited at 450nm.
The dynamic ranges of the calibration graphs are 100-10,000ngmL-1 for all the
antibiotics assayed and the limits of detection are in the range of 44-51ngmL-1.
The precision, established at two concentration levels of each analyte and
expressed as the percentage of the relative standard deviation is in the range of
6.9-9.8%. The method has been satisfactorily applied to the analysis of water and
pharmaceutical samples, with recoveries ranging from 88.6% to 108.5%.
PMID- 28501181
TI - A voltammetry sensor platform for baicalein and baicalin simultaneous detection
in vivo based on Ta2O5-Nb2O5@CTS composite.
AB - Baicalein and baicalin are the major flavonoids found in Scutellariae Radix, an
essential herb which has had a presence in traditional Chinese medicine (TCMs)
for more than two thousands of years. Owing to their similar characteristics and
physiochemical properties, sensitive, it is a great challenge to detect both of
them simultaneously. In this work, a novel, facile and sensitive electrochemical
method was proposed based on tantalum oxide (Ta2O5), niobium oxide (Nb2O5)
particles and antiseptic chitosan modified carbon paste electrode (Ta2O5
Nb2O5@CTS-CPE). Scanning electron microscope (SEM), X-ray diffraction
spectroscopy (XRD), Fourier transform infrared spectroscopy (FTIR), cyclic
voltammetry (CV) and electrochemical impedance spectrum (EIS) were used to
characterize the properties and investigate the electrochemical response of the
sensor. The electrochemical behaviors and redox mechanisms of two analytes were
investigated at the target electrode. Under the optimum conditions, the highly
sensitive and simultaneous determination of baicalein and baicalin was
successfully achieved with a linear response range of 0.08-8.0MUM for both of
them. The obtained detection limits for baicalein and baicalin were of 0.05 and
0.03MUM (S/N=3), respectively. Furthermore, the proposed sensor displayed high
sensitivity, excellent stability and satisfactory results in Scutellariae Radix
samples analysis and hydrolysis process analysis of baicalin in vivo.
PMID- 28501180
TI - Detection of Abeta oligomers based on magnetic-field-assisted separation of
aptamer-functionalized Fe3O4 magnetic nanoparticles and BaYF5:Yb,Er nanoparticles
as upconversion fluorescence labels.
AB - A sensitive and stable bioassay for the detection of Abeta oligomer (Abetao), a
potentially promising candidate biomarker for Alzheimer's disease (AD) diagnosis,
was developed using Fe3O4 magnetic nanoparticles (MNPs) as the recognition and
concentration elements and BaYF5:Yb,Er upconversion nanoparticles (UCNPs) as
highly sensitive labels, conjugated with the Abetao aptamer (DNA1) and the
complementary oligonucleotide of the Abetao aptamer (DNA2), respectively. The
DNA1 hybridized with DNA2 to form the duplex structure on the surface of the
MNPs/UCNPs nanocomposites probe. When the target Abetao was introduced, the
aptamer DNA1 preferentially bound with Abetao and caused the dissociation of some
complementary DNA2, liberating some UCNP-labeled complementary DNA2 and leading
to a decreased upconversion fluorescent intensity on the surface of MNPs. The
decreased fluorescence intensity of UCNPs was related to the concentration of
Abetao in the range of 0.2-15nM with a detection limit of 36 pM. The developed
method then was successfully applied to measure Abetao in artificial
cerebrospinal fluid. Benefiting from the magnetic separation and concentration
effect of MNPs, the high sensitivity of UCNPs, as well as the selectivity and
stability of the aptamer, the present strategy offered valuable information
related to early diagnosis of AD process.
PMID- 28501182
TI - Determination of Escherichia coli in urine using a low-cost foil-based
microfluidic device.
AB - We developed a simple low-cost cultivation-based microfluidic device from office
laminator foil and Parafilm for the determination of specific microorganisms in
water samples. The main goal was to obtain a device that would be portable and
cheap compared to common laboratory techniques testing microorganisms. This
device needs only 10uL of a sample and can be easily used in terrain by a non
specialist. Moreover, we dealt with some technical aspects of the device
fabrication such as low-cost lamination techniques and the use of different
cultivation media.
PMID- 28501183
TI - In-line moisture monitoring in fluidized bed granulation using a novel multi
resonance microwave sensor.
AB - Microwave resonance technology (MRT) is known as a process analytical technology
(PAT) tool for moisture measurements in fluid-bed granulation. It offers a great
potential for wet granulation processes even where the suitability of near
infrared (NIR) spectroscopy is limited, e.g. colored granules, large variations
in bulk density. However, previous sensor systems operating around a single
resonance frequency showed limitations above approx. 7.5% granule moisture. This
paper describes the application of a novel sensor working with four resonance
frequencies. In-line data of all four resonance frequencies were collected and
further processed. Based on calculation of density-independent microwave moisture
values multiple linear regression (MLR) models using Karl-Fischer titration (KF)
as well as loss on drying (LOD) as reference methods were build. Rapid, reliable
in-process moisture control (RMSEP<=0.5%) even at higher moisture contents was
achieved.
PMID- 28501184
TI - Heavy metal contents of play dough, face and finger paint samples sold in turkish
markets.
AB - Lead, cadmium, nickel, manganese, cobalt and copper contents of some play dough,
face and finger paint samples were determined by using a new solid phase
extraction method which has been developed by using multi-walled carbon nanotube
with patent blue (V) sodium salt to selectively separate and preconcentrate these
metal ions. Flame atomic absorption spectrometry was used to determine the metal
ions. Analytical parameters affecting the complex formation and solid phase
extraction performance such as pH, the amount of ligand and volume of sample
solution were investigated. The recoveries of the studied metal ions were not
affected by the foreign ions. Analytes were recovered quantitatively at pH 5.5
and with a nitric acid of 2molL-1 as eluent. Analysis of a certified reference
material was performed to validate the method before applying it to determine the
metal ions in the real samples. Detection limits were found to be as Pb(II):
7.71MUgL-1, Cu(II): 1.43MUgL-1, Cd(III): 0.21MUgL-1, Mn(II): 0.47MUgL-1, Ni(II):
3.52MUgL-1and Co(II): 1.96MUgL-1.
PMID- 28501185
TI - Simultaneous voltammetric determination of vanillin and caffeine in food products
using an anodically pretreated boron-doped diamond electrode: Its comparison with
HPLC-DAD.
AB - This paper describes an electroanalytical method for the simultaneous
determination of vanillin (VAN) and caffeine (CAF) using an anodically pretreated
boron-doped diamond electrode. Selective determination of one compound in the
presence of other one was also realized. Both compounds yielded a single
irreversible oxidation peak using cyclic voltammetry. The nature of the electrode
reaction was found to be diffusion controlled with contribution of adsorption. By
using square-wave adsorptive stripping voltammetry after 60s accumulation under
open-circuit voltage, method allowed simultaneous determination of VAN and CAF in
phosphate buffer, pH 2.5, with detection limits of 0.234ugmL-1 (1.54*10-6M) and
0.071ugmL-1 (3.66*10-7M), respectively. The proposed method was successfully
applied in the selective and simultaneous determination of VAN and CAF in
commercial food and beverage samples. In addition, for the comparison, high
performance liquid chromatographic method with diode-array detection was
developed for the first time for their simultaneous determination.
PMID- 28501186
TI - Application of Box-Behnken design to optimize multi-sorbent solid phase
extraction for trace neonicotinoids in water containing high level of matrix
substances.
AB - Extensive use of neonicotinoid insecticides has raised great concerns about their
ecological risk. A reliable method to measure trace neonicotinoids in complicated
aquatic environment is a premise for assessing their aquatic risk. To effectively
remove matrix interfering substances from field water samples before instrumental
analysis with HPLC/MS/MS, a multi-sorbent solid phase extraction method was
developed using Box-Behnken design. The optimized method employed 200mg HLB/GCB
(w/w, 8/2) as the sorbents and 6mL of 20% acetone in acetonitrile as the elution
solution. The method was applied for measuring neonicotinoids in water at a wide
range of concentrations (0.03-100MUg/L) containing various amounts of matrix
components. The recoveries of acetamiprid, imidacloprid, thiacloprid and
thiamethoxam from the spiked samples ranged from 76.3% to 107% while clothianidin
and dinotefuran had relatively lower recoveries. The recoveries of neonicotinoids
in water with various amounts of matrix interfering substances were comparable
and the matrix removal rates were approximately 50%. The method was sensitive
with method detection limits in the range of 1.8-6.8ng/L for all target
neonicotinoids. Finally, the developed method was validated by measurement of
trace neonicotinoids in natural water.
PMID- 28501187
TI - Voltammetric determination of reduced glutathione using poly(thionine) as a
mediator in the presence of Fenton-type reaction.
AB - An indirect and sensitive electrochemical method for the determination of reduced
glutathione (GSH) was developed by using poly(thionine) (PTH) as a mediator in
the presence of Fenton-type reaction on the electrode surface in this work.
Cyclic voltammetry and the adsorption of Cu2+ were employed in sequence to
fabricate a Cu-PTH modified electrode, which was characterized by scanning
electron microscopy, XPS and electrochemical measurements. Hydroxyl radicals that
were derived from the Fenton-type reaction between Cu2+ and H2O2 could
effectively oxidize PTH, leading to the great enhancement of the cathodic peak
current of the dye polymer in the cyclic voltammetric scan. The electroreduction
of PTH on the electrode surface was found to be inhibited in the presence of GSH.
Under the optimized conditions, the cathodic peak current change was found to be
proportional to the logarithm of the GSH concentration from 10nM to 1mM with a
detection limit of 2.5nM estimated at a signal-to-noise ratio of 3. The proposed
electrochemical sensor was successfully employed for the determination of GSH in
real samples with satisfactory results.
PMID- 28501188
TI - A hemicyanine-based colorimetric and ratiometric fluorescent probe for selective
detection of cysteine and bioimaging in living cell.
AB - A new ratiometric fluorescent probe based on a hemicyanine dye was synthesized.
Investigation on the response behavior towards amino acids showed that the probe
had a capability of rapidly and selectively detecting cysteine over other
biothiols such as glutathione and homocysteine with similar structure and
reactivity, and it also displayed a high selectivity and rapid response.
Moreover, the probe had good water solubility, which authorized it could be
applied in fluorescent bioimaging. The laser confocal fluorescence images
indicated that the probe could visualize the intracellular cysteine. This work
suggested that it could be utilized as a fluorescent indicator to discriminate
the endogenous cysteine in living cells.
PMID- 28501189
TI - High selective potentiometric sensor for determination of nanomolar con
centration of Cu(II) using a polymeric electrode modified by a graphene/7,7,8,8
tetracyanoquinodimethane nanoparticles.
AB - In this paper we present several possibilities for modification of the all-solid
state copper(II)-selective electrodes in order to obtain high stability and
selectivity potentiometric sensor signal. The copper(II)-selective electrodes
were modified in a simple way by introducing solid contact layer based on
graphene or graphene oxide, 7,7,8,8-tetracyanoquinodimethane or its copper salt.
Each of electrodes shown a Nernstian response, wide linear range of Cu2+
concentration and a low detection limit. Nevertheless, some differences between
the groups of electrodes have been noticed and resulted from application of
intermediate layers of various compositions. The electrode modified with graphene
and 7,7,8,8-tetracyanoquinodimethane nanocomposite exhibited the best potential
reproducibility and detection limit. Moreover, prepared sensors were
characterized by an improved selectivity for copper(II) in relation to non
modified electrodes. The developed electrodes were successfully used for the Cu2+
determination in different samples and results were comparable with those
obtained using voltammetry.
PMID- 28501190
TI - HPLC-UV and HPLC-CAD chromatographic data fusion for the authentication of the
geographical origin of palm oil.
AB - Data fusion combined with a multivariate classification approach (partial least
squares-discriminant analysis, PLS-DA) was applied to authenticate the
geographical origin of palm oil. Data fusion takes advantage of the synergistic
effect of information collected from more than one data source. In this study,
data from liquid chromatography coupled to two detectors -ultraviolet (UV) and
charged aerosol (CAD)- was fused by high- and mid-level data fusion strategies.
Mid-level data fusion combines a few variables from each technique and then
applies the classification technique. Principal component analysis and interval
partial least squares were applied to obtain the variables selected. High-level
data fusion combines the PLS-DA classification results obtained individually from
the chromatographic technique with each detector. Fuzzy aggregation connective
operators were used to make the combinations. Prediction rates varied between 73%
and 98% for the individual techniques and between 87% and 100% and 93% and 100%
for the mid- and high-level data fusion strategies, respectively.
PMID- 28501191
TI - TLC-UV hyphenated with MALDI-TOFMS for the screening of invertase substrates in
plant extracts.
AB - In this study, thin-layer chromatography (TLC) hyphenated with matrix-assisted
laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) was
developed for the screening of invertase substrates in complex matrices. BfrA, a
specific beta-D-fructofuranosidase from Leishmania major, was chosen as a model
enzyme to screen biological activity in plant extracts due to its capacity to
hydrolyze specific carbohydrates. TLC was considered to be a reliable technique
for screening substrates (bioactive molecules) in plant extracts due to its
quantitative capabilities whereas MALDI-TOFMS was particularly useful for rapid
identification. The first part of this approach consisted of a differential
analysis by TLC-densitometry to highlight band under- and over-expressions in
plant extract between blank and enzymatic reaction. Zones of interest were then
immediately analyzed by TLC-MALDI-TOFMS coupling to identify bioactive molecules.
Development of the method presented various challenges: the separation and
analysis of isomers (such as glucose and fructose), the high matrix effect
(demonstrated by the analysis of products with invertase enzyme naturally present
in plant extract), and the analysis of polar molecules with low molecular mass
(sugars). Thanks to the separative technique, the specificity of detection, and
the high precision of the characterization, this method was shown to be feasible
for the analysis of bioactive molecules in complex mixtures containing
interfering compounds (e.g. proteins, salts). Overall, this study demonstrates
that Thin-layer chromatography hyphenated with Matrix-assisted laser
desorption/ionization time-of-flight mass spectrometry is a simple, rapid,
precise and efficient method for the analysis of suitable substrates in raw
samples.
PMID- 28501192
TI - Variability of fluorescence spectra of coelenteramide-containing proteins as a
basis for toxicity monitoring.
AB - Nowadays, physicochemical approach to understanding toxic effects remains
underdeveloped. A proper development of such mode would be concerned with
simplest bioassay systems. Coelenteramide-Containing Fluorescent Proteins (CLM
CFPs) can serve as proper tools for study primary physicochemical processes in
organisms under external exposures. CLM-CFPs are products of bioluminescent
reactions of marine coelenterates. As opposed to Green Fluorescent Proteins, the
CLM-CFPs are not widely applied in biomedical research, and their potential as
colored biomarkers is undervalued now. Coelenteramide, fluorophore of CLM-CFPs,
is a photochemically active molecule; it acts as a proton donor in its electron
excited states, generating several forms of different fluorescent state energy
and, hence, different fluorescence color, from violet to green. Contributions of
the forms to the visible fluorescence depend on the coelenteramide
microenvironment in proteins. Hence, CLM-CFPs can serve as fluorescence
biomarkers with color differentiation to monitor results of destructive
biomolecule exposures. The paper reviews experimental and theoretical studies of
spectral-luminescent and photochemical properties of CLM-CFPs, as well as their
variation under different exposures - chemicals, temperature, and ionizing
radiation. Application of CLM-CFPs as toxicity bioassays of a new type is
justified.
PMID- 28501193
TI - Immunoaffinity chromatography combined with tandem mass spectrometry: A new tool
for the selective capture and analysis of brassinosteroid plant hormones.
AB - Brassinosteroids (BRs) are plant-specific steroid hormones that play essential
roles in the regulation of many important physiological processes in plant life.
Their extremely low concentrations (~pmoles/g FW) in plant tissue and huge
differences in polarity of individual members within the BR family hamper their
detection and quantification. To address this problem, an immunoaffinity sorbent
with broad specificity and high capacity for different BR metabolites containing
a monoclonal antibody (mAb) against a BR spacer (20S)-2alpha,3alpha-dihydroxy-7
oxa-7alpha-homo-5alpha-pregnane-6-one-20 carboxylic acid (BR4812) was used for
the rapid and highly selective isolation of endogenous BRs containing a
2alpha,3alpha-diol in ring A from minute plant samples. This enrichment procedure
was successfully applied as a sample preparation method prior to quantitative
analysis of BRs in real plant tissues by ultra-high performance liquid
chromatography-tandem mass spectrometry (UHPLC-MS/MS). Use of immunoaffinity
chromatography (IAC) increased the sensitivity of the UHPLC-MS/MS analysis owing
to improvements in the BR signal-to-noise ratio (S/N) and matrix factor (MF).
Although MF values of BRs analyzed in classical samples ranged from 8.9% to
47.4%, MF values for the IAC purified samples reached 44.5-96.6%. Thus, the
developed IAC-UHPLC-MS/MS approach was shown to be a simple, robust, effective
and extremely fast procedure requiring minute amounts of plant samples suitable
for the quantitative profiling of many BR metabolites, helping to overcome the
major problems associated with their determination in very complex plant
matrices.
PMID- 28501194
TI - The use of Stationary Phase Optimized Selectivity Liquid Chromatography for the
development of herbal fingerprints to detect targeted plants in plant food
supplements.
AB - The consumption of plant food supplements is increasing steadily and more and
more, these products are bought through internet. Often the products sold through
internet are not registered or declared with a national authority, meaning that
no or minimal quality control is performed and that they could contain herbs or
plants that are regulated. Stationary Phase Optimized Selectivity Liquid
Chromatography (SOS-LC) was evaluated for the development of specific
fingerprints, to be used for the detection of targeted plants in plant food
supplements. Three commonly used plants in plant food supplements and two
regulated plants were used to develop fingerprints with SOS-LC. It was shown that
for all plants specific fingerprints could be obtained, allowing the detection of
these targeted plants in triturations with different herbal matrices as well as
in real samples of suspicious supplements seized by the authorities. For three of
the five plants a more specific fingerprint was obtained, compared to the ones
developed on traditional columns described in literature. It could therefore be
concluded that the combination of segments of different types of stationary
phases, as used in SOS-LC, has the potential of becoming a valuable tool in the
quality control and the identification of crude herbal or plant material and in
the detection of regulated plants in plant food supplements or other herbal
preparations.
PMID- 28501195
TI - Recycling polymer residues to synthesize magnetic nanocomposites for dispersive
micro-solid phase extraction.
AB - The ubiquitous presence of plastics, an obvious consequence of their usefulness
and low price, has turned them into a problem of environmental and safety
concern. The new plastic economy, an initiative recently launched by the World
Economic Forum and Ellen MacArthur Foundation, with analytical support from
McKinsey & Company, promotes a change in the use of plastic worldwide around
three main pillars: redesign, reusing and recycling. Recycled plastics, with the
aim of extending their life spam, can be used to synthesize materials for
analytical purposes. In this article polystyrene (PS) trays, previously used for
food packaging, are proposed as polymeric source for the synthesis of magnetic
nanocomposites. The synthesis plays with the solubility of PS in different
solvents in such a way that PS is gelated in the presence of cobalt ferrite
nanoparticles which are finally embedded in the polymeric network. The extraction
capability of the magnetic PS nanocomposite was evaluated using the determination
of four parabens (methylparaben, ethylparaben, propylparaben and butylparaben) in
water using liquid chromatography-tandem mass spectrometry as model analytical
problem. Under the optimum conditions, limits of detection and quantification
were in the range of 0.05-0.15 and 0.15-0.5ng/mL, respectively. The precisions,
expressed as relative standard deviation (RSD), varied between 4.4% and 8.5% and
the relative recoveries for analysis of the water samples were in the interval
81.2-104.5%.
PMID- 28501196
TI - Calibration transfer between different analytical methods.
AB - The procedure for transfer of calibration models between different analytical
methods is suggested. It is based on the direct standardization (DS) algorithm
earlier suggested for data conversion between physically different instruments of
the same type. As a result, multivariate regression models obtained e.g. for NIR
spectroscopic measurements in one wavelength range can be successfully applied
for predictions from the data obtained with another NIR spectrometer in another
wavelength range. The performance of the suggested method was tested with two
simulated and two real datasets. In the latter case calibration models
constructed for energy-dispersive X-ray fluorescence, UV-Vis spectrometry and NIR
spectrometry were addressed. The observed performance of the method implies that
it can have a broad range of possible applications in analytical chemistry; some
of them are suggested in the paper.
PMID- 28501197
TI - Methylmercury determination in seafood by photochemical vapor generation
capacitively coupled plasma microtorch optical emission spectrometry.
AB - A non-chromatographic method based on double liquid-liquid extraction and
measurements by UV photochemical vapor generation capacitively coupled plasma
microtorch optical emission spectrometry was developed and characterized for
methylmercury determination in seafood. Samples were prepared following the
procedure recommended in JRC Technical Report of European Commission formerly
proposed for the determination of methylmercury in seafood by thermal
decomposition atomic absorption spectrometry, namely confinement of Hg species in
47% HBr solution, extraction of CH3Hg+ in toluene and back-extraction in 1% l
cysteine aqueous solution. Mercury cold vapor was generated by flow injection UV
photo-reduction from CH3Hg+ in 0.6molL-1 HCOOH, while quantification was
performed against external Hg2+ aqueous standards and measuring Hg 253.652nm
emission using a low power/Ar consumption plasma microtorch (15W, 100mLmin-1) and
a low resolution microspectrometer (Ocean Optics). The figures of merit and
analytical capability were assessed by analyzing certified reference materials
and test samples of fish fillet and discussed in relation with requirements for
Hg determination in seafood in European legislation (Decisions 2007/333/EC and
2002/657/EC) as well as compared to performances achieved in thermal
decomposition atomic absorption spectrometry. The limit of detection and
quantification of 2ugkg-1 and 6ugkg-1 respectively, precision of 2.7-9.4% and
accuracy of 99+/-8% of the proposed method for the determination of CH3Hg+
fulfill the demands of European legislation for Hg quantification. The limit of
detection and quantification were better than those in the used reference method
or other non-/chromatographic methods taken for comparison. The analysis of
certified reference materials and the Bland and Altman test performed on 12 test
samples confirmed trueness of the proposed method and its reliability for the
determination of traces of CH3Hg+ with 95% confidence level. The proposed method
fulfills several demands of the eco-scale concept, is sensitive, simple and safe
related to sample preparation through elimination of classical, harmful
reductants and attractive by using economical miniaturized instrumentation
incorporating a low power and low Ar consumption plasma.
PMID- 28501198
TI - Introducing plasma/serum glycodepletion for the targeted proteomics analysis of
cytolysis biomarkers.
AB - A major class of clinical biomarkers is constituted of intracellular proteins
which are leaking into the blood following ischemia, exposure to toxic
xenobiotics or mechanical aggression. Their ectopic presence in plasma/serum is
an indicator of tissue damage and raises a warning signal. These proteins,
referred to as cytolysis biomarkers, are generally of cytoplasmic origin and as
such, are devoid of glycosylation. In contrast, most plasma/serum proteins
originate from the hepatic secretory pathway and are heavily glycosylated (at the
exception of albumin). Recent advances in targeted proteomics have supported the
parallelized evaluation of new blood biomarkers. However, these analytical
methods must be combined with prefractionation strategies that reduce the
complexity of plasma/serum matrix. In this article, we present the glycodepletion
method, which reverses the hydrazide-based glycocapture concept to remove
plasma/serum glycoproteins from plasma/serum matrix and facilitates the detection
of cytolysis biomarkers. Glycodepletion was integrated to a targeted proteomics
pipeline to evaluate 4 liver cytolysis biomarker candidates in the context of
acetaminophen-induced acute hepatitis.
PMID- 28501199
TI - Developing a sensor layer for the optical detection of amines during food
spoilage.
AB - A colourimetric sensor layer has been developed for ammonia and biogenic amines.
Amine exposure induces a traffic light colour change from green to red.
Recognition is performed by a pH indicator dye, covalently immobilised onto
cellulose microparticles. The sensor microparticles are embedded into food-grade
silicone. Selectivity of the pH indicator dye towards gaseous amine is obtained
by complete embedding of the sensor particles within the ion-impermeable
silicone. A response time of 1.5h has been achieved, with a reverse response
occurring after 20h. This time frame is considered sufficient for spoilage
processes. Cytotoxicity studies confirm the layers are non-toxic.
PMID- 28501200
TI - A new approach to calibration and determination of selected trace elements in
food contact polymers by LA-ICP-MS.
AB - A calibration strategy using porous nylon disks and reference solutions is
proposed for the first time for matrix matching and determination of As, Ba, Cd,
Cr, Pb, Sr and Zn in polymers by laser ablation-inductively coupled plasma mass
spectrometry (LA-ICP-MS). Polymer samples commonly used in contact with food were
analyzed. The procedure consists on the use of porous nylon disks as support for
a dried droplet reference solution. Calibration in the range of 0.50-190MUgg-1
for Ba, Cd, Cr, Pb, Sr and Zn and from 0.30-9.0MUgg-1 for As was used. Laser and
ICP-MS instrument conditions were evaluated in order to achieve the best signal
to-background ratio. The radiofrequency power and carrier gas flow rate were
fixed at 1300W and 1.25Lmin-1, respectively. Spot size, repetition rate, scan
line speed and laser fluency were set to 100um, 20Hz, 100ums-1 and 17.9Jcm-2,
respectively, as the established conditions for analysis of standards and
samples. By using these conditions, limits of detection, estimated considering
B+3s (where B is the value of the blank and s is the standard deviation of 10
measurements of the blank), ranged from 0.09MUgg-1 (208Pb) to 1.09 (53Cr) and
0.05MUgg-1 (208Pb) to 2.10 (53Cr) for calibration with and without 13C as
internal standard (IS). In spite to the use of nylon for matrix matching of
different polymeric matrices, the normalization with 13C as IS was also
evaluated. The precision of the method is relatively good (RSD<20%), and the
accuracy of the method, evaluated by analysis of certified reference materials
(CRM) and by comparison with results obtained from solution analysis by ICP-MS
after sample decomposition by microwave induced combustion (MIC) is relatively
good. The suitability of the proposed method resulted in direct and reliable
analyses of polymer samples with a simplified or unnecessary sample preparation
step. In addition, the calibration with dried droplet reference solutions may be
considered a promising procedure in view of its advantages to other forms of
calibration, as the use of CRM or the preparation of synthetic standards. The use
of porous nylon disks spiked with reference solutions for calibration is the main
advantage of the present work.
PMID- 28501201
TI - Waste derivitized blue luminescent carbon quantum dots for selenite sensing in
water.
AB - Herein, we report an environmental friendly, facile, and completely green
synthetic method for producing carbon quantum dots (CQDs) from whey, a major
dairy waste. The as-prepared monodispersed diameter CQDs exhibit blue
luminescence with noteworthy quantum yield (~11.4%) and excitation dependent
emission behaviour. Nuclear magnetic resonance (NMR) analysis reveals the
presence of aromatized carbon peaks, leading to polymerized CQDs diameter
architecture during whey pyrolysis. The X-ray and selected area electron
diffraction patterns confirm their amorphous nature. Further, we demonstrate,
these CQDs as an effective sensor probe for selective selenite monitoring in
water upon functionalization with appropriate ligand. The functionalized GCQDs
probe is shown to detect selenite with high sensitivity in 10-1000ppb detection
range. Further it is selective for selenite over other relevant ions (such as
Cu2+, As3+, As5+, Pb2+, Ni2+, Se6+, Cl-, Br-, NO3-, NO2- and F-) and displays a
sub-ppb detection limit at 1.1% relative standard deviation.
PMID- 28501202
TI - A ratiometric fluorescent probe for hypochlorous acid determination: Excitation
and the dual-emission wavelengths at NIR region.
AB - An interesting ratiometric fluorescent probe with unique optical performance was
reported in this work. By modifying on the bridge-head of heptamethine cyanine
chromophore with an N-phenyl-N'-ethylene amine thiourea substituent as a
chemodosimetric recognition unit, the probe exhibited ratiometric fluorescent
response towards hypochlorous acid (HClO). Upon addition of HClO, the absorbance
spectra showed a great red shift as large as 150nm from 650nm to 800nm. Employing
the isosbestic absorption point at 730nm as an excitation wavelength, a
ratiometric fluorescent sensing mode with two long emission wavelengths at 760nm
and 820nm was acquired, and thus the probe displayed significant behavior with
both the excitation wavelength and the dual-emission wavelengths located at NIR
(650-900nm) region exclusively. Also, the probe showed excellent performance in
high sensitivity and good selectivity towards HClO over other reactive oxygen
species and a wide variety of coexist species in biological pH condition and had
been successfully used to detect hypochlorous acid in serum samples and tap water
samples.
PMID- 28501203
TI - Development of a progesterone immunosensor based on thionine-graphene oxide
composites platforms: Improvement by biotin-streptavidin-amplified system.
AB - Progesterone (P4) is a kind of hormone that can cause neuropathic disturbances in
humans when the concentration overpasses a certain degree. In this work, an
electrochemical immunosensor capable of detecting P4 sensitively and selectively
was developed. Thionine-graphene oxide (Thi-GO) composites with excellent
biocompatibility were synthesized and coated to a clear glassy carbon electrode.
P4 coating antigen (P4-OVA) was immobilized to the electrode, then sample as well
as biotinylated antibody (biotin-P4 Ab) were added. The free P4 can compete with
P4-OVA for binding to biotin-P4 Ab. After the further addition of streptavidin
HRP, H2O2 was introduced to develop electrical signal for quantitative
determination of P4. After careful optimization of assay conditions, the proposed
immunosensor showed a linear range from 0.02 to 20ngmL-1 for P4 in milk samples.
The averaged recoveries from spiked samples ranged from 84.0% to 102.0%, which
correlated well with standard HPLC-MS/MS. The biosensor also showed good
specificity, reproducibility and stability, indicating its potential application
in monitoring of P4 in a simple and low cost manner.
PMID- 28501204
TI - Quantification of N-glycosylation site occupancy status based on labeling/label
free strategies with LC-MS/MS.
AB - Protein N-glycosylation plays important roles in physiological and pathological
processes. Characterizing the site-specific N-glycosylation including N-glycan
macroheterogeneity (glycosylation site occupancy) and microheterogeneity (site
specific glycan structure) is important for understanding of glycoprotein
biosynthesis and function. N-Glycan macroheterogeneity is a physiological
property of glycoprotein and the technical obstacles have restricted research
into the regulation and functions of this heterogeneity. Quantification of N
glycosylation site occupancy would uncover the critical role of
macroheterogeneity in a variety of biological properties. Liquid chromatography
(LC)- mass spectrometry (MS)-based quantification is emerging as a powerful tool
for glycosylation characterization. This review summarizes the labeling and label
free quantitative MS approaches for quantifying N-glycosylation site occupancy,
including its quantification for target glycoproteins in recent years.
PMID- 28501205
TI - An integrated strategy for the quantitative analysis of endogenous proteins: A
case of gender-dependent expression of P450 enzymes in rat liver microsome.
AB - Liquid chromatography mass spectrometry based methods provide powerful tools for
protein analysis. Cytochromes P450 (CYPs), the most important drug metabolic
enzymes, always exhibit sex-dependent expression patterns and metabolic
activities. To date, analysis of CYPs based on mass spectrometry is still facing
critical technical challenges due to the complexity and diversity of CYP isoforms
besides lack of corresponding standards. The aim of present work consisted in
developing a label-free qualitative and quantitative strategy for endogenous
proteins, and then applying to the gender-difference study for CYPs in rat liver
microsomes (RLMs). Initially, trypsin digested RLM specimens were analyzed by the
nanoLC-LTQ-Orbitrap MS/MS. Skyline, an open source and freely available software
for targeted proteomics research, was then used to screen the main CYP isoforms
in RLMs under a series of criteria automatically, and a total of 40 and 39 CYP
isoforms were identified in male and female RLMs, respectively. More importantly,
a robust quantitative method in a tandem mass spectrometry-multiple reaction mode
(MS/MS-MRM) was built and optimized under the help of Skyline, and successfully
applied into the CYP gender difference study in RLMs. In this process, a simple
and accurate approach named 'Standard Curve Slope" (SCS) was established based on
the difference of standard curve slopes of CYPs between female and male RLMs in
order to assess the gender difference of CYPs in RLMs. This presently developed
methodology and approach could be widely used in the protein regulation study
during drug pharmacological mechanism research.
PMID- 28501206
TI - Simultaneous determination and speciation analysis of arsenic and chromium in
iron supplements used for iron-deficiency anemia treatment by HPLC-ICP-MS.
AB - This work proposes the use of high performance liquid chromatography coupled to
inductively coupled plasma mass spectrometry (HPLC-ICP-MS) for simultaneous
speciation of arsenic and chromium in iron supplements used for the treatment of
anemia. The sample preparation procedure recommended for the total determination
of arsenic and chromium was established using acid digestion in a microwave
assisted oven. For speciation analysis, however, the microwave-assisted
extraction procedure involved the use of water as extraction solvent at 90
degrees C for 30min. The chromatographic separation was performed using a mobile
phase containing 1.0mM tetrabutylammonium hydroxide (TBAH), 0.7mM
ethylenediaminetetraacetic acid (EDTA) and 5% methanol at pH 7.2. Helium was used
in the collision cell for elimination of the interferences. Under optimized
conditions, the separation and detection of the As(III), As(V), Cr(III) and
Cr(VI) species can be performed in 5min, permitting their quantification with the
external calibration technique with standards prepared in the mobile phase. The
limits of quantification obtained were 0.008, 0.010, 0.5 and 0.14ugg-1, for
As(III), As(V), Cr(III) and Cr(VI), respectively. The accuracy of the method was
evaluated and confirmed by addition/recovery tests. The recoveries obtained
varied from 81% to 110%. The proposed method was applied to the speciation
analysis of arsenic and chromium in commercially available iron supplements
acquired in several cities in Brazil and Spain. The content of the species ranged
from 0.01 to 1.3ugg-1 for arsenic, and from 0.4 to 61.2ugg-1 for chromium.
PMID- 28501207
TI - Novel bimetallic gold-silver nanoclusters with "Synergy"-enhanced fluorescence
for cyanide sensing, cell imaging and temperature sensing.
AB - We herein opened up a facile and green strategy for the fabrication of bright
orange-fluorescent gold-silver nanoclusters (AuAgNCs@ew, GSNCs) by a one-pot
synthesis at a vital molar ratio of Au/Ag precursors in the egg white protein
matrix using microwave-assisted method. The prepared GSNCs exhibited enhanced
fluorescence with fluorescent quantum yield of 5.4%, which is dependent on gold
and silver synergies. Due to the advantageous superiority of low-toxicity,
excellent stability and satisfactory fluorescence, the as-prepared GSNCs has been
successfully used in cell imaging and temperature sensing. More strikingly, the
GSNCs emerged strong response to CN- with rapid, selective, and ultrasensitive
characteristics. The detection limit was approximately 138nM, which is nearly 20
times lower than the maximum level (2700nM) of CN- in drinking water set up by
the World Health Organization (WHO). In addition, the as-prepared GSNCs could be
applied to detecting real samples with minimum interference. Our findings showed
that this new GSNCs probe is eco-friendly and large-scale development for
potential applications including the detection of environmental pollution and
bioimaging.
PMID- 28501208
TI - Evaluation of a QuEChERS-like extraction approach for the determination of PBDEs
in mussels by immuno-assay-based screening methods.
AB - A sample preparation method was evaluated for the determination of polybrominated
diphenyl ethers (PBDEs) in mussel samples, by using colorimetric and
electrochemical immunoassay-based screening methods. Herein, a rapid procedure
based on QuEChERS-like extraction approach followed by solid phase purification
was optimized for PBDE extraction from mussel samples. The detection limits for
colorimetric and electrochemical immunoassays, calculated as BDE-47 equivalent
concentration, were 0.6ngg-1 and 1.1ngg-1, respectively. Real mussel samples,
including a Certified Reference Material (CRM), were analyzed. The samples were
measured by colorimetric and electrochemical immunoassays as well as by GC-MS. In
comparison to GC-MS results, 106% and 102% relative accuracy were obtained for
the colorimetric and electrochemical immunoassays, respectively. The proposed
method could be useful for massive environmental campaigns, being able to rapidly
detect possible polluted seafood samples.
PMID- 28501209
TI - A sensitive signal-off electrogenerated chemiluminescence biosensing method for
the discrimination of DNA hydroxymethylation based on glycosylation modification
and signal quenching from ferroceneboronic acid.
AB - In this study, a new and sensitive signal-off electrogenerated chemiluminescence
(ECL) biosensing method for the quantification of 5-hydroxymethylcytosine in DNA
(5-hmC-DNA) was developed. The method achieved simple and sensitive detection of
5-hmC-DNA based on the glycosylation of 5-hmC, combining both the amplification
function of gold nanoparticles (AuNPs) and the high quenching efficiency of the
tris(2, 2'-ripyridine) dichlororuthenium(II) (Ru(bpy)32+)-ferrocene (Fc) system.
First, the electrode modified with a mixture of Nafion and AuNPs was utilized as
the platform for electrostatically adsorbing Ru(bpy)32+(an ECL-emitting species)
and assembling 5-hmC-DNA. The 5-hmC-DNA was glycosylated by T4 beta
glucosyltransferase, yielding beta-glucosyl-5-hydroxymethyl-cytosine in DNA (5
ghmC-DNA). Finally, quencher-FcBA was further covalently bound to 5-ghmC-DNA
through formation of boronate ester covalent bonds between boronic acid and cis
diols of 5-ghmC, resulting in a decrease in ECL intensity. The results indicated
that the decreased ECL intensity was directly linear to the concentration of 5
hmC-DNA in the range from 1.0*10-8 to 5.0*10-11M with a low detection limit of
1.63*10-11M. In addition, this ECL method was demonstrated to be useful for the
quantification of 5-hmC in clinical serum samples. Moreover, the method allowed
good discrimination among cytosine (5-C), 5-methylcytosine (5-mC), and 5-hmC in
DNA.
PMID- 28501210
TI - Determination of tocopherols and their metabolites by liquid-chromatography
coupled with tandem mass spectrometry in human plasma and serum.
AB - Several studies are increasingly underlying the biological role of vitamin E
metabolites as bioactive compounds with anti-inflammatory, anti-proliferative and
anti-atherogenic activity. A quantitative method for the simultaneous
determination in human plasma and serum of vitamin E (alpha-tocopherol, alpha-T
and gamma-tocopherol, gamma-T) and its cytochrome P-450 metabolites: 13'
hydroxychromanol (alpha-13'-OH), 13'-carboxychromanol (alpha-13'-COOH) and
carboxyethyl hydroxychromanols (alpha-CEHC and gamma-CEHC), was developed and
validated. After enzymatic hydrolysis and deproteinization, the metabolites were
extracted with a mixture of hexane/ methyl tertiary butyl ether (2/1, v/v). The
separation was achieved by reversed phase chromatography and the analytes
detected by a triple quadrupole mass analyser using electrospray ionization in
positive mode (LC-MS/MS). alpha-T and gamma-T were extracted separately without
enzymatic hydrolysis. The analytes were quantified with the isotopic dilution
method. After an extensive validation study (three levels in three different
occasions for a total of 54 experiments), the procedure was successfully applied
to the analysis of sera of healthy volunteers (before and after supplementation
with alpha-T) and plasma of patients affected by chronic kidney disease. Finally,
the structures of three unknown compounds found in blood and related to the long
chain metabolites (alpha-13'-OH and alpha-13'-COOH) were further investigated
using liquid chromatography coupled to high resolution mass spectrometry (LC
HRMS).
PMID- 28501211
TI - Metastatic cancer cell and tissue-specific fluorescence imaging using a new DNA
aptamer developed by Cell-SELEX.
AB - Metastasis, which derived from a primary tumor, accounts for 90% of mortality
caused by cancer. Early diagnosis of cancer metastasis may significantly improve
cure rate of patients who are at high risk for developing metastasis. In this
study, we successfully achieved metastatic cancer cell and tissue-specific
fluorescence imaging by using a new aptamer developed by cell-based systematic
evolution of ligands by exponential enrichment (Cell-SELEX). With metastatic
colorectal carcinoma LoVo cells as selection target, the aptamer named J3 which
bind to metastatic cancer cells with good affinity and specificity was obtained.
Then J3 was labeled with Cy5 fluorescent group (J3-Cy5) for imaging metastatic
cancer cells, the results demonstrated excellent imaging contrast. Moreover, the
results of tissue section imaging revealed that J3-Cy5 probe explicitly
recognized lymph node tissue with colorectal carcinoma metastasis with a high
detection rate of 73.9%, but showed a low detection rate to colorectal carcinoma
tissue with no metastasis or cancer adjacent tissue. Therefore, the targeting
reagent J3-based fluorescence imaging possesses great potential for clinical
diagnosis of cancer metastasis.
PMID- 28501213
TI - Corrigendum to "Magnetic graphene solid-phase extraction for the determination of
carbamate pesticides in tomatoes coupled with high performance liquid
chromatography [TAL 141 212-219]".
PMID- 28501212
TI - A selective and sensitive fluorescent probe for the determination of HSA and
trypsin.
AB - A simple fluorescent probe HBI-GR based on the combination of the fluorophore (p
HBI) in green fluorescent protein (GFP) and Guanine riboside (GR) for HSA was
successfully synthesized. HBI-GR showed an obvious fluorescence enhancement
toward HSA without interference from other proteins, amino acids, anions and
commonly existing metal ions. HBI-GR exhibited high sensitivity towards HSA with
a good linear relationship between the fluorescence intensity of HBI-GR and HSA
concentration from 0 to 0.06mgmL-1. The limit of detection, based on a signal-to
noise ratio of 3, was 15.09ngmL-1, which was much lower than that of most other
reported probes. HBI-GR was almost non-fluorescent because of the bond twisting
in the exited state of chromophore HBI. After binding to the hydrophobic pocket
of HSA, it showed an obvious fluorescence enhancement due to the rigidifying of
the flexible chromophore HBI by the hydrophobic environment. The resulting HBI
GR/HSA system also showed a satisfactory sensing ability toward trypsin through
decreased fluorescence intensity with the detection limit of 0.0282ngmL-1. The
fluorescence decreasing process was occurred as the lysine and arginine amino
acids residues of HSA were cleaved by trypsin, which led to further exposure of
HBI-GR to the PBS buffer phase and a concomitant decrease of the HBI-GR
fluorescence intensity. Moreover, the probe HBI-GR was successfully used to
detect HSA in healthy human urine and human blood serum samples. The practical
application of the HBI-GR/HSA system for trypsin detection in healthy human urine
also achieved satisfactory result.
PMID- 28501215
TI - Assessment of in vitro dopamine-neuroblastoma cell interactions with a
bioelectric biosensor: perspective for a novel in vitro functional assay for
dopamine agonist/antagonist activity.
AB - Current receptor-binding assays for dopamine do not measure the in vitro whole
cellular response against dopamine or potential agonist/antagonist molecules. We
herewith report the development of a novel functional assay concept for studying
the in vitro interaction of the neurotransmitter dopamine with neural cells
bearing dopamine receptors. The concept is based on the ultra-rapid measurement
of changes in the electric properties of cultured N2a mouse neuroblastoma cells
(corresponding to cumulative changes of the cell membrane potential). A close
relationship between cumulative cell membrane potential and dopamine
concentration was observed. Membrane depolarization was observed at nanomolar
dopamine concentrations, while hyperpolarization was associated with micromolar
ones. Treatment with the dopamine D2-receptor antagonist eticlopride resulted to
a concentration-dependent membrane depolarization. Treatment with sodium chloride
caused considerable weakening of the dopamine-associated hyperpolarization
effect. The observed bioelectric response to dopamine was highly inversely
correlated with the pattern of dopamine release-uptake balance by N2a cells, as
determined with cyclic voltammetry. The bioelectric approach was also used to
evaluate the dopaminergic activity of chaste tree (Vitex agnus-castus) extracts.
The novel assay concept offers promising perspectives for the development of
advanced companion diagnostics system for the high throughput, fast functional
characterization of neurotransmitter agonists and antagonists.
PMID- 28501216
TI - Intracellular DNA and microRNA sensing based on metal-organic framework
nanosheets with enzyme-free signal amplification.
AB - A new fluorescent sensing platform based on ultrathin metal-organic framework
(MOF) nanosheets (MnDMS) was prepared from the flexible ligand 2,2
dimethylsuccinate and Mn ions. The MnDMS nanoparticles can be obtained by simply
ultrasonication of the MnDMS crystal, and then can be exfoliated into nanosheets
by Li-intercalation method. The MnDMS nanosheets can be easily assembled with
biological probes, leading to efficient fluorescence quenching of the fluorophore
tagged ssDNA and microRNA (miRNA). By using a hybridization chain reaction (HCR)
strategy, the fluorescence signal can be obviously amplified. A good linearity
was obtained from 1 pM to 200 pM of target ssDNA, with a detection limit of 0.2
pM. The HCR/MnDMS system provides an effective way to monitor miRNA in living
cells. Therefore, the MnDMS nanosheets can be used as a new kind of platform in
biomedical sensing applications.
PMID- 28501214
TI - Capillary electrophoresis tandem mass spectrometry determination of glutamic acid
and homocysteine's metabolites: Potential biomarkers of amyotrophic lateral
sclerosis.
AB - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects
both lower and upper motor neurons, leading to muscle atrophy, paralysis, and
death caused by respiratory failure or infectious complications. Altered levels
of homocysteine, cysteine, methionine, and glutamic acid have been observed in
plasma of ALS patients. In this context, a method for determination of these
potential biomarkers in plasma by capillary electrophoresis tandem mass
spectrometry (CE-MS/MS) is proposed herein. Sample preparation was carefully
investigated, since sulfur-containing amino acids may interact with plasma
proteins. Owing to the non-thiol sulfur atom in methionine, it was necessary to
split sample preparation into two methods: i) determination of homocysteine and
cysteine as S-acetyl amino acids; ii) determination of glutamic acid and
methionine. All amino acids were separated within 25min by CE-MS/MS using 5molL-1
acetic acid as background electrolyte and 5mmolL-1 acetic acid in 50%
methanol/H2O (v/v) as sheath liquid. The proposed CE-MS/MS method was validated,
presenting RSD values below 6% and 11% for intra- and inter-day precision,
respectively, for the middle concentration level within the linear range. The
limits of detection ranged from 35 (homocysteine) to 268nmolL-1 (glutamic acid).
The validated method was applied to the analysis of plasma samples from a group
of healthy individuals and patients with ALS, showing the potential of glutamic
acid and homocysteine metabolites as biomarkers of ALS.
PMID- 28501217
TI - EDTA-functionalized magnetic nanoparticles: A suitable platform for the analysis
of low abundance urinary proteins.
AB - Urine is a highly attractive source of biological information and disease
biomarkers, whose proteome characterization is ongoing. To that end,
depletion/enrichment strategies for protein analysis can be of great convenience.
We have thus developed a method based on the use of EDTA-functionalized magnetic
nanoparticles (NPs@EDTA), to fractionate urine samples before liquid
chromatography-mass spectrometry analysis and compared the identified proteins
with those obtained from ultrafiltrated/unfractionated (UF) urine samples.
NPs@EDTA allowed larger urine volumes to be processed, resulting in a greater
number of protein identifications (~2-fold) at a lower cost when compared to UF
samples. Proteins of greater abundance (such as albumin and uromodulin) were, at
least partially, depleted with NPs@EDTA while those of lower abundance were
enriched. Bioinformatics analysis showed that approximately 27% of NPs@EDTA
enriched proteins were annotated as displaying enzymatic activity, most of these
being hydrolytic enzymes (56%), particularly proteases/peptidases (48%). Also,
post-translational modifications were prominently predicted across NPs@EDTA
enriched proteins (90%), particularly glycosylation (52%), phosphorylation (47%)
and acetylation (30%). NPs@EDTA allowed the identification of 109 proteins in
urine for the first time, showing high potential as a platform for urine's
fractionation prior to proteomic analysis.
PMID- 28501218
TI - A modified fluorescein derivative with improved water-solubility for turn-on
fluorescent determination of Hg2+ in aqueous and living cells.
AB - To improve the water-solubility of heavy-metal sensing materials, a modified
fluorescein-based derivative, acryloyl fluorescein hydrazine (ACFH), was designed
and developed by incorporating a non-hydrogen-bonding group into the conjugated
molecule for weakening intermolecular hydrogen-bonding interactions. In neutral
water environments, ACFH presented a fluorescence-enhancement performance at
lambdamax=512nm in the presence of Hg2+, which could be visualized by naked-eyes.
Under the optimized conditions, the linear range of Hg2+ detection was 1.0-100*10
9molL-1 with a correlation coefficient of 0.9992 and a detection limit of 0.86*10
9molL-1. The recognition mechanism was confirmed to be a stable and irreversible
1:1 five-member ring complex between ACFH and Hg2+ with a coordination constant
of 3.36*109. ACFH would possess a potential application in detecting Hg2+ for
biological assay with low cytotoxicity.
PMID- 28501219
TI - Headspace single-drop microextraction coupled with microvolume fluorospectrometry
for highly sensitive determination of bromide.
AB - This work reports on the development of a novel methodology for bromide
determination by combining headspace single-drop microextraction with microvolume
fluorospectrometry. The method lies in the in situ generation of bromine,
transfer of the volatile to the headspace and trapping/reaction onto a
fluorescein-containing aqueous drop exposed to the gas phase. The decrease in the
fluorescence intensity enabled the determination of bromide without dilution of
the enriched microdrop. Experimental parameters influencing the performance of
the method, namely, fluorescence parameters, extractant phase composition,
bromine generation conditions and microextraction time, were evaluated and
controlled. Under optimal conditions, an enrichment factor of 243 was attained.
The limits of detection and quantification achieved under optimal conditions for
bromide were found to be 1.4 and 4.4ugL-1, respectively. The intra-day
repeatability, expressed as relative standard deviation, was 4.4% (n=6). Besides,
the inter-day reproducibility, performed at four different days, was 7.1%.
Finally, the developed method was successfully applied to the determination of
bromide in different water samples, showing recovery values in the range of 95
110%, and validated against certified reference material BCR-611 (ground water,
Br- low level). The proposed method represents a highly convenient approach for
monitoring of bromide at very low concentrations.
PMID- 28501220
TI - 7,8-hydroxy-2'-deoxyguanosine/2'-deoxiguanosine ratio determined in hydrolysates
of brain DNA by ultrachromatrography coupled to tandem mass spectrometry.
AB - 7,8-hydroxy-2'-deoxyguanosine (8-OHdG) is an abundant DNA lesion formed by
oxidation of the nucleoside 2'-deoxyguanosine (2-dG) and one of the most studied
and accepted oxidative stress biomarkers. 8-OHdG has a strong carcinogenic
potential, and prolonged oxidative stress heightens pathological conditions and
especially cancer risk. Our aim was to develop, validate and apply a reliable
method to assess DNA oxidation in genomic cellular DNA of sensible target organs
such as brain. A procedure to isolate and digest the DNA of brain tissue properly
for further detection of 8-OHdG and 2-dG by Ultra Performance Liquid
Chromatography-tandem Mass Spectrometry (UPLC-MS/MS) was optimized. The UPLC
MS/MS was validated following the American Food and Drug Administration (FDA)
Guidelines using mice pups' brain samples. To demonstrate the applicability of
the UPLC-MS/MS method, 8-OHdG/2-dG ratio was determined in brain tissue of 1day
old newborn mice pups (P1) in a model of hypoxia pre-conditioning during fetal-to
neonatal transition. We found that hypoxia at birth (FiO2 0.14) and for 8h
thereafter induced lower levels of DNA oxidation in mice pups and rendered even
protective against a postnatal asphyxia/reoxygenation insult compared with fetal
to neonatal transition in room air. We conclude that the UPLC-MS/MS method
developed has proven suitable for the analysis of DNA oxidation biomarker 8
OHdG/2-dG ratio in tissue samples from newborn mice pups. We aim to apply this
method in future studies aiming to provide a deeper insight into the mechanisms
of oxidation DNA caused during neonatal asphyxia and resuscitation.
PMID- 28501221
TI - Return to Sport and Clinical Outcomes After Hip Arthroscopic Labral Repair in
Young Amateur Athletes: Minimum 2-Year Follow-Up.
AB - PURPOSE: To determine the rate of return of young amateur athletes to sport after
hip arthroscopy, their clinical outcomes, and pathologic risk factors for worse
outcomes 2 years after surgery. METHODS: This study included all patients between
age 13 and 23 who participated in a sport prior to surgery with intent to return
who underwent hip arthroscopy after failure of comprehensive nonoperative
management for whom 2-year outcome scores were available. Outcomes collected
retrospectively included modified Harris Hip Score (mHHS) and the Hip Outcome
Scores (HOS) subscales for activities of daily living (ADL) and sport (HOS
Sport). In addition, sport played, return to sport rates, and Tegner Scores were
measured preinjury and postoperatively. Descriptive statistics were used to
present demographic data. A priori analysis was used to determine the sample size
needed to show minimal clinically important differences for mHHS, HOS ADL, and
HOS Sport. RESULTS: The study population included 50 patients with a mean age of
17.8 years. Athletes returned to sport at a rate of 92% (46/50). At a mean follow
up of 34 months, the mean mHHS, HOS ADL, and HOS Sport outcome scores were 85,
91, and 80 for the entire study group; 87, 92, and 84 for the group that returned
to sport; and 67, 82, and 41 for the group that did not return to sport,
respectively. Median preinjury and postoperative Tegner levels were 8 and 7,
respectively. Labral takedown and reattachment was associated with lower HOS ADL
(P = .01) and HOS Sport scores (P = .02). CONCLUSIONS: Athletes returned to sport
at a high rate (92%; 46/50) after hip arthroscopy and perform activities at near
preinjury levels. In this group of athletes, arthroscopic labral repair with
chondrolabral preservation, which reflected less severe chondrolabral pathology,
performed better than labral repair with takedown and reattachment. LEVEL OF
EVIDENCE: Level IV, therapeutic case series.
PMID- 28501222
TI - Medial Patellar Instability: A Systematic Review of the Literature of Outcomes
After Surgical Treatment.
AB - PURPOSE: To perform a systematic review of literature reporting on outcomes after
surgical treatment of medial patellar instability. METHODS: A systematic review
was performed according to PRISMA guidelines. Inclusion criteria were as follows:
the outcomes and complications of medial patellar instability repair with a
follow-up greater than 12 months, English language, and human studies. We
excluded cadaveric studies, animal studies, basic science articles, editorial
articles, review articles, and surveys. RESULTS: Searches identified 1,116
individual titles. After inclusion and exclusion criteria were applied, a total
of 8 studies were identified. Three studies exclusively included patients with
previous lateral release; 1 included patients with chronic instability; 1
included patients with both previous lateral release and other surgical causes; 1
study had patients with previous lateral release, spontaneous instability, and
instability due to injury; 1 study included patients after tibial tubercle
transfer surgery; and 1 study did not report the etiology of instability.
CONCLUSIONS: Good to excellent outcomes were reported postoperatively in 85% of
the patients after surgical treatment of medial patellar instability. However,
clinical outcomes data for medial patellar ligament reconstruction is sparse and
highly heterogeneous. There is inconsistency in the literature in regard to the
indication, timing, and procedure. LEVEL OF EVIDENCE: Level IV, systematic review
of Level IV studies.
PMID- 28501223
TI - Health care barriers, racism, and intersectionality in Australia.
AB - While racism has been shown to negatively affect health care quality, little is
known about the extent to which racial discrimination works with and through
gender, class, and sexuality to predict barriers to health care (e.g., perceived
difficulty accessing health services). Additionally, most existing studies focus
on racial disparities in the U.S. context, with few examining marginalized groups
in other countries. To address these knowledge gaps, we analyze data from the
2014 Australian General Social Survey, a nationally representative survey of
individuals aged 15 and older living in 12,932 private dwellings. Following an
intersectional perspective, we estimate a series of multivariable logit
regression models to assess three hypotheses: racial discrimination will be
positively associated with perceived barriers to health care (H1); the effect of
perceived racial discrimination will be particularly severe for women, sexual
minorities, and low socio-economic status individuals (H2); and, in addition to
racial discrimination, other forms of perceived discrimination will negatively
impact perceived barriers to health care (H3). Findings show that perceptions of
racial discrimination are significantly associated with perceived barriers to
health care, though this relationship is not significantly stronger for low
status groups. In addition, our analyses reveal that perceived racism and other
forms of discrimination combine to predict perceived barriers to health care.
Taken together, these results speak to the benefits of an intersectional approach
for examining racial inequalities in perceived access to health care.
PMID- 28501224
TI - Re: Pascal Rischmann, Albert Gelet, Benjamin Riche, et al. Focal High Intensity
Focused Ultrasound of Unilateral Localized Prostate cancer: A Prospective
Multicentric Hemiablation Study of 111 Patients. Eur Urol 2017;71:267-73.
PMID- 28501225
TI - Introduction to Integrative Medicine in the Primary Care Setting.
AB - Integrative Medicine has been described as "healing oriented medicine that takes
account of the whole person (body, mind, and spirit) including all aspects of
lifestyle. It emphasizes therapeutic relationships and makes use of all
appropriate therapies, both conventional and alternative." National surveys
consistently report that approximately one-third of adults and 12% of children
use complementary and integrative medicine approaches. Although there are
barriers to primary care professionals engaging in discussions about lifestyle
change and complementary and integrative medicine options, there is also great
potential to impact patient well-being.
PMID- 28501226
TI - Phytotherapy: An Introduction to Herbal Medicine.
AB - Herbal medications are commonly used in all medical settings, making it essential
for primary care providers to learn about the products being used and resources
they can access for continuing education. Understanding how herbal medicines are
sourced, processed, and standardized can help providers guide patients who are
trying to choose the most clinically effective and affordable treatments.
Multiple herbs are often combined and sold as proprietary blends, which can
increase the risk of allergies, adverse reactions, or cross-reactivity with other
pharmaceuticals and supplements. Several textbooks, online point-of-care
resources, and conferences are available for primary care providers to expand
their knowledge of herbal medicines.
PMID- 28501227
TI - Integrative Medicine Strategies for Changing Health Behaviors: Support for
Primary Care.
AB - Until system reforms allow adequate time and reimbursement for primary care
providers to focus on lifestyle change to prevent and mitigate chronic disease,
primary care providers need a manageable, defined role to support lifestyle
change. The authors suggest this role is to serve as a catalyst, priming the
patient for change; educating and pointing the patient to appropriate, evidence
based resources for additional guidance and hands-on support; and providing
ongoing encouragement throughout the long journey of change while patients work
more intensely with health coaches or allied health providers.
PMID- 28501228
TI - Integrative Medicine for the Treatment of Persistent Pain.
AB - Integrative health modalities can provide useful tools in the management of
persistent pain in the primary care setting. These modalities, such as
acupuncture, mind-body medicine, diet and herbs, and movement strategies can be
safely used and may provide patients with hope and empowerment. It is highly
recommended that the patient work alongside trained professionals for a given
modality and/or an interprofessional team.
PMID- 28501230
TI - Integrative Medicine and Mood, Emotions and Mental Health.
AB - An integrative approach to individuals with mood, emotional or mental health
concerns involves a comprehensive model of care that is person-centered.
Integrative medicine builds on a patient's personal meaning and goals (spiritual
aspects) and includes herbal therapies, nutritional support, movement and
physical manipulative therapies, mindfulness, relaxation strategies, and
psychotherapies.
PMID- 28501231
TI - Complementary and Integrative Interventions for Chronic Neurologic Conditions
Encountered in the Primary Care Office.
AB - Chronic neurologic conditions are frequently managed in the primary care setting,
and patients with these conditions are increasingly seeking nonconventional
treatment options. This article provides a review and summary of the evidence for
some of the most commonly studied and most frequently used complementary and
integrative interventions for 3 conditions managed every day in primary care
offices - diabetic neuropathy, migraine, and dementia.
PMID- 28501232
TI - Restoring Balance for People with Cancer Through Integrative Oncology.
AB - Integrative Oncology incorporates conventional and western cancer treatment
approaches with the best of ancient and traditional medicine including nutrition,
supplements, Qigong, herbal medicine, mind-body practices, and more. This article
offers a guiding conceptual paradigm from an integrative perspective based on the
principles of balance and imbalance. An integrative approach is used to help
improve quality of life, enhance lifestyle choices and mitigate symptoms and side
effects from conventional treatments. By supporting the patient's mind, body and
spirit throughout the cancer treatment journey, the primary care physician is in
a key position to work with their patient's oncologist to provide supportive care
and recommendations during cancer treatment.
PMID- 28501229
TI - Integrative Medicine for Gastrointestinal Disease.
AB - Gastrointestinal conditions are prevalent in the population and account for
significant morbidity and health care costs. Patients with gastrointestinal
conditions use integrative medicine. There is growing evidence that integrative
medicine approaches can improve symptoms and affect physiology and disease
course. This article reviews data on some common and well-studied approaches,
including mind-body therapies, acupuncture, diet, probiotics, and dietary
supplements and herbs. Although clear recommendations can be made for some
conditions, in others there are challenges in translating these findings owing to
small study size, lack of standardization, and trial heterogeneity.
PMID- 28501233
TI - Pediatric Integrative Medicine.
AB - The practice of pediatrics from an integrative framework is based on physician
patient relationship, informed by evidence, and approaches the health of children
and their families from a broad perspective. This article reviews the basic
principles of integrative pediatrics and summarizes data and integrative
approaches to common pediatric conditions seen in the primary care setting.
PMID- 28501234
TI - Integrative Medicine and Cardiovascular Disorders.
AB - Integrative medicine (IM) has developed an increasingly significant role in
health care worldwide, including cardiovascular diseases (CVD). This review
describes the commonly used IM in CVD, with particular attention placed with
dietary supplements and mind-body therapies. More rigorous research continues to
be needed to determine the mechanisms and efficacy of IM cardiovascular morbidity
and mortality. Health care providers will need to develop skills in open
communication and nonjudgmental dialogue around IM use in discussing treatment
plans with their patients.
PMID- 28501235
TI - Women's Health: Pregnancy and Conception.
AB - Preconception is an ideal time to assist women contemplating pregnancy to modify
health behaviors. Dietary needs in pregnancy are critical and may require
supplementation. The use of mind-body medicine in the antenatal period assists
patients in childbirth preparation. Integrative medicine techniques can be safely
and effectively used for common third-trimester obstetric complications of
pregnancy.
PMID- 28501236
TI - Women's Health: Polycystic Ovarian Syndrome, Menopause, and Osteoporosis.
AB - Surveys consistently show that a significantly higher percentage of women with
chronic medical conditions report use of complementary and integrative medicine
(CIM) approaches compared with men. A total of 54.5% of women report use of at
least one CIM approach specifically for obstetric or gynecologic problems.
However, primary care providers remain an underutilized resource by patients for
guidance in the safe and appropriate use of integrative therapies. This article
provides a practical overview of the most appropriate integrative therapies to
consider in the management of commonly seen women's health conditions: polycystic
ovarian syndrome, menopause, and osteoporosis.
PMID- 28501237
TI - "Too Much?"
PMID- 28501238
TI - Integrative Medicine and Primary Care.
PMID- 28501239
TI - Economic Insecurity and Intimate Partner and Sexual Violence Victimization.
AB - INTRODUCTION: Previous research has consistently found that low SES is associated
with higher levels of both intimate partner violence (IPV) and sexual violence
(SV) victimization. Though associated with poverty, two indicators of economic
insecurity, food and housing insecurity, have been identified as conceptually
distinct social determinants of health. This study examined the relationship
between food and housing insecurity experienced in the preceding 12 months and
IPV and SV victimization experienced in the preceding 12 months, after
controlling for SES and other demographic variables. METHODS: Data were from the
2010 National Intimate Partner and Sexual Violence Survey, a nationally
representative telephone survey of U.S. adults. In 2016, multivariate logistic
regression modeling was used to examine the association between food and housing
insecurity and multiple forms of IPV and SV victimization. RESULTS: Robust
associations were found between food and housing insecurity experienced in the
preceding 12 months and IPV and SV experienced in the preceding 12 months, for
women and men, even after controlling for age, family income, race/ethnicity,
education, and marital status. CONCLUSIONS: Food and housing insecurity may be
important considerations for the prevention of SV and IPV or the reductions of
their consequences, although future research is needed to disentangle the
direction of the association. Strategies aimed at buffering economic insecurity
may reduce vulnerability to IPV and SV victimization.
PMID- 28501240
TI - Urinary Excretion of alpha1-Microglobulin Does Not Predict Graft Loss in Stable
Kidney Transplant Recipients.
PMID- 28501241
TI - In Reply to 'Urinary Excretion of alpha1-Microglobulin Does Not Predict Graft
Loss in Stable Kidney Transplant Recipients'.
PMID- 28501242
TI - Colorectal Cancer Screening.
AB - This article highlights the importance of colorectal cancer screening in the
prevention and early detection of colorectal cancer. Early detection of
colorectal cancer is associated with reduced mortality. There are a variety of
screening procedures for colorectal cancer, which are variable in technique and
effectiveness. Engaging patients to participate in a screening regimen with which
they will comply is critical to the ultimate success of colorectal cancer
screening. Familiarity with risk stratification and screening guidelines is
imperative for counseling and appropriate testing.
PMID- 28501243
TI - Imaging for Colorectal Cancer.
AB - A comprehensive approach to colorectal cancer includes thorough radiologic
imaging, which allows appropriate initial staging of the disease, as well as
subsequent surveillance for disease recurrence. Several imaging modalities are
used with different associated advantages and disadvantages, which are outlined
in this article with specific attention paid to the local staging of rectal
cancer.
PMID- 28501244
TI - The Difficult Colorectal Polyp.
AB - Difficult colorectal polyps represent lesions that pose a challenge to
traditional endoscopic snare polypectomy. These polyps have historically been
managed by surgical resection. Currently, several less invasive options are
available to avoid colectomy. Repeat colonoscopy and snare polypectomy by an
expert endoscopist, endoscopic mucosal resection, endoscopic submucosal
dissection, and combined endoscopic and laparoscopic surgery have been developed
to remove difficult polyps without the need for formal surgical resection.
Patients with rectal polyps have the advantage of additional transanal minimally
invasive techniques to enhance their resectability. Today, most colorectal polyps
can be managed without the need for formal surgical resection.
PMID- 28501245
TI - Emergency Presentations of Colorectal Cancer.
AB - Many colorectal carcinomas will present emergently with issues such as
obstruction, perforation, and bleeding. Emergency surgery is associated with poor
short- and long-term outcomes. For abnormality localizing to the colon proximal
to the splenic flexure, surgical management with hemicolectomy is often a safe
and appropriate approach. Obstructions are more common in the distal colon,
however, where there is an evolving spectrum of surgical and nonsurgical options,
most notably by the development of endoluminal stents. Perforation and bleeding
are managed similarly to benign causes, as malignancy may be only part of a
differential diagnosis at the time of an operation.
PMID- 28501247
TI - Robotic Colorectal Surgery for Neoplasia.
AB - Robotic colorectal surgery has become increasingly prevalent, with several
reported benefits for surgeons and patients alike. Although its use is well
supported for pelvic surgery, there is less evidence that it is beneficial for
abdominal surgery. There are several technical limitations of robotic surgery,
and newer generations of robot platforms have addressed these, which may lead to
increased use in the near future. In general, robotic surgery is more beneficial
for surgeons than it is for patients.
PMID- 28501246
TI - Advances in Laparoscopic Colorectal Surgery.
AB - Laparoscopic colorectal surgery has now become widely adopted for the treatment
of colorectal neoplasia, with steady increases in utilization over the past 15
years. Common minimally invasive techniques include multiport laparoscopy, single
incision laparoscopy, and hand-assisted laparoscopy, with the choice of technique
depending on several patient and surgeon factors. Laparoscopic colorectal surgery
involves a robust learning curve, and fellowship training often lays the
foundation for a high-volume laparoscopic practice. This article provides a
summary of the various techniques for laparoscopic colorectal surgery, including
operative steps, the approach to difficult patients, and the learning curve for
proficiency.
PMID- 28501248
TI - Local Excision of Rectal Cancer.
AB - Local excision (LE) of early-stage rectal cancer avoids the morbidity associated
with radical surgery but has historically been associated with inferior oncologic
outcomes. Newer techniques, including transanal endoscopic microsurgery (TEM) and
transanal minimally invasive surgery (TAMIS), have been developed to improve the
quality of LE and extend the benefits of LE to tumors in the more proximal
rectum. This article provides an overview of conventional LE, TEM, and TAMIS
techniques, including indications for their use and pertinent literature on their
associated outcomes for rectal cancer.
PMID- 28501249
TI - New Strategies in Rectal Cancer.
AB - In recent years, our understanding of rectal cancer has improved, including how
locally advanced disease responds to chemotherapy and radiation. This has led to
new innovations and advances in the treatment of rectal cancer, which includes
organ-preserving strategies for responsive disease, and minimally invasive
approaces for the performance of total mesorectal excision/protectomyh for
persistently advanced disease. This article discusses new strategies for rectal
cancer therapy, including Watch and Wait, local excision, minimally invasive
proctectomy, and transanal total mesorectal excision particularly in the setting
of preoperative multimodality treatment.
PMID- 28501250
TI - Hereditary Colorectal Cancer Syndromes.
AB - Awareness of hereditary colorectal cancer syndromes is important to facilitate
their identification because affected patients are at increased risk for early
onset, synchronous, and metachronous colorectal malignancies, and certain
extracolonic malignancies depending on the syndrome. Identification of an
affected individual allows for screening and early interventions for patients and
their at-risk kindred. Genetic counseling and testing is important to the care of
these patients. As knowledge of the genetic basis of these syndromes grows,
unique genotype-phenotype profiles allow clinicians to tailor surveillance and
treatment strategies based on individual risk.
PMID- 28501251
TI - Dysplasia and Cancer in Inflammatory Bowel Disease.
AB - Inflammatory bowel disease is associated with an increased risk of dysplasia and
cancer. Improvements in medical management and endoscopic surveillance have
reduced these risks. Patients can develop cancer even in the absence of dysplasia
or with indefinite or low-grade dysplasia. Most guidelines recommend starting
surveillance colonoscopy 6 to 10 years after initial diagnosis with interval
surveillance afterward every 1 to 5 years depending on risk and/or individual
characteristics. Most patients should undergo total proctocolectomy with end
ileostomy or reconstruction with ileal pouch anal anastomosis because segmental
and subtotal resections carry a higher risk of metachronous cancers.
PMID- 28501252
TI - Atypical Colorectal Neoplasms.
AB - Primary colorectal lymphoma, carcinoids (neuroendocrine tumors), and
gastrointestinal stromal tumors comprise a small subset of all colorectal
cancers. Their features are unique, and their treatment varies from that of
colorectal adenocarcinoma. Appropriate identification is key in the management of
these tumors.
PMID- 28501254
TI - Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy in the Management of
Colorectal Peritoneal Metastasis.
AB - Historically, patients with peritoneal carcinomatosis secondary to colorectal
cancer have a poor overall prognosis. Recent data support the use of
cytoreductive surgery and heated intraperitoneal chemotherapy (CRS + HIPEC) to
specifically address the peritoneal disease. Retrospective studies on CRS + HIPEC
have been promising, showing significant improvements in OS compared with
systemic chemotherapy alone. However, CRS + HIPEC carries morbidity similar to
other advance oncology procedures such as liver resection and
pancreatoduonectomy. It is hoped that ongoing clinical trials will clarify its
role in the treatment of patients with peritoneal metastatic colorectal cancer.
PMID- 28501253
TI - Resection of the Primary Tumor in Stage IV Colorectal Cancer: When Is It
Necessary?
AB - Management of metastatic colorectal cancer requires accurate staging and
multidisciplinary evaluation, leading to a consensus treatment plan with the
ultimate goal of increasing survival and improving the quality of life, while
taking into consideration the patient's performance status, disease burden, and
goals of care. Since the introduction of multidrug chemotherapeutic regimens,
survival of patients with metastatic colorectal cancer has improved. Many
patients with unresectable disease are undergoing surgery for asymptomatic
primary tumors despite evidence that it is usually a futile intervention.
Palliative measures for local control of the primary tumor include colonic
stents, laser therapy, and fulguration.
PMID- 28501256
TI - Foreword.
PMID- 28501255
TI - Molecular Markers for Colorectal Cancer.
AB - Colorectal cancers develop through at least 3 major pathways, including
chromosomal instability, mismatch repair, and methylator phenotype. These
pathways can coexist in a single individual and occur in both sporadic and
inherited colorectal cancers. In spite of the unique molecular and genetic
signatures of colorectal cancers, nonspecific chemotherapy based on the
antineoplastic effects of 5-fluorouracil is the cornerstone of therapy for stage
III and some stage II disease. Techniques to recognize colorectal cancer at the
molecular level have facilitated development of new signature drugs designed to
inhibit the unique pathways of colorectal cancer growth and immunity.
PMID- 28501257
TI - Preface.
PMID- 28501258
TI - Impact of Hospital Admission for Patients with Transient Ischemic Attack.
AB - OBJECTIVES: To determine the impact of admission among transient ischemic attack
(TIA) patients in the emergency department (ED). STUDY DESIGN: Retrospective
cohort study using national Veterans Health Administration data (2008). METHODS:
We first analyzed whether admitted patients were discharged from the hospital
with a diagnosis of TIA. We then analyzed whether admission was associated with a
composite outcome (new stroke, new myocardial infarction, or death in the year
after TIA) using multivariate logistic regression modeling with propensity score
matching. RESULTS: Among 3623 patients assigned a diagnosis of TIA in the ED,
2118 (58%) were admitted to the hospital or placed in observation compared with
1505 (42%) who were discharged from the ED. Among the 2118 patients who were
admitted, 903 (43% of admitted group) were discharged from the hospital with a
diagnosis of TIA, and 548 (26% of admitted group) were discharged with a
diagnosis of stroke. Admitted patients were more likely than nonadmitted patients
to receive processes of care (i.e., brain imaging, carotid imaging,
echocardiography). In matched analyses using propensity scores, the 1-year
composite outcome in the admitted group (15.3%) was not lower than the discharged
group (13.3%, OR 1.17 [.94-1.46], P = .17). CONCLUSIONS: Less than half of
patients admitted with a diagnosis of TIA retained that diagnosis at hospital
discharge. Although admitted patients were more likely to receive diagnostic
procedures, we did not identify improvements in outcomes among admitted patients;
however, evaluating care for patients with TIA is limited by the reliability of
secondary data analysis.
PMID- 28501260
TI - Erratum to "Efficacy and tolerability of adjunctive brivaracetam in patients with
prior antiepileptic drug exposure: A post-hoc study" [Epilepsy Res. 131 (2017) 70
75].
PMID- 28501259
TI - Risk of Stroke/Transient Ischemic Attack or Myocardial Infarction with Herpes
Zoster: A Systematic Review and Meta-Analysis.
AB - BACKGROUND: Accumulating evidence indicates that herpes zoster (HZ) may increase
the risk of stroke/transient ischemic attack (TIA) or myocardial infarction (MI),
but the results are inconsistent. We aim to explore the relationship between HZ
and risk of stroke/TIA or MI and between herpes zoster ophthalmicus (HZO) and
stroke. METHODS: We estimated the relative risk (RR) and 95% confidence intervals
(CIs) with the meta-analysis. Cochran's Q test and Higgins I2 statistic were used
to check for heterogeneity. RESULTS: HZ infection was significantly associated
with increased risk of stroke/TIA (RR = 1.30, 95% CI: 1.17-1.46) or MI (RR =
1.18, 95% CI: 1.07-1.30). The risk of stroke after HZO was 1.91 (95% CI 1.32
2.76), higher than that after HZ. Subgroup analyses revealed increased risk of
ischemic stroke after HZ infection but not hemorrhagic stroke. The risk of stroke
was increased more at 1 month after HZ infection than at 1-3 months, with a
gradual reduced risk with time. The risk of stroke after HZ infection was greater
with age less than 40 years than 40-59 years and more than 60 years. Risk of
stroke with HZ infection was greater without treatment than with treatment and
was greater in Asia than Europe and America but did not differ by sex.
CONCLUSIONS: Our study indicated that HZ infection was associated with increased
risk of stroke/TIA or MI, and HZO infection was the most marked risk factor for
stroke. Further studies are needed to explore whether zoster vaccination could
reduce the risk of stoke/TIA or MI.
PMID- 28501261
TI - Obsessive Compulsive Symptoms and Quality of Life in mothers of Children With
Atopic Dermatitis.
AB - BACKGROUND AND OBJECTIVES: Atopic dermatitis is one of the most common skin
disorders in children and it can negatively affect both children and their
families. The purpose of this study was to investigate the effect of atopic
dermatitis on quality of life related to maternal health and maternal obsessive
compulsive symptoms. METHODS: A cross-sectional study was conducted in the
pediatric and dermatology polyclinics. The SCORAD index was used for determining
the severity of disease, and the Maudsley Obsessive Compulsive Inventory (MOCI)
and SF-36 form were applied to the participants' mothers. RESULTS: A total of 120
children and their mothers participated the study. Comparing the atopic
dermatitis group and the healthy control group, no statistically significant
differences were seen in terms of MOCI and SF-36 scores, except for the physical
functioning subscore. CONCLUSION: The results showed that having a child with
atopic dermatitis and the severity of the disease do not influence their mothers
in terms of obsessive-compulsive symptoms and health-related quality of life,
except for physical functioning scores.
PMID- 28501262
TI - Radiotherapy in nonmelanoma skin cancer: Radiosensitivity, radioresistance and
radiocurability. In regard to Gracia-Cazana et al.
PMID- 28501263
TI - Economic and environmental review of Waste-to-Energy systems for municipal solid
waste management in medium and small municipalities.
AB - The application of Directive 2008/98/CE on Municipal Solid Waste (MSW) implies
the need to introduce technologies to generate energy from waste. Incineration,
the most widely used method, is difficult to implement in low populated areas
because it requires a large amount of waste to be viable (100,000 tons per year).
This paper analyses the economic and environmental costs of different MSW-to
Energy technologies (WtE) in an area comprising of 13 municipalities in southern
Spain. We analyse anaerobic digestion (Biomethanization), the production of solid
recovered fuel (SRF) and gasification, and compare these approaches to the
present Biological Mechanical Treatment (BMT) with elimination of the reject in
landfill, and incineration with energy recovery. From an economic standpoint the
implementation of WtE systems reduces the cost of running present BMT systems and
incineration; gasification presents the lowest value. From the environmental
standpoint, Life Cycle Assessment shows that any WtE alternatives, including
incineration, present important advantages for the environment when compared to
BMT. Finally, in order to select the best alternative, a multi-criteria method is
applied, showing that anaerobic digestion is the optimal solution for the area
studied.
PMID- 28501264
TI - Challenges around automotive shredder residue production and disposal.
AB - The challenge for the automotive industry is how to ensure they adopt the
circular economy when it comes to the disposal of end-of-life vehicles (ELV).
According to the European Commission the UK achieved a total reuse and recovery
rate of 88%. This is short of the revised ELV directive target of 95% materials
recovery, which requires a minimum of 85% of materials to be recycled or reused.
A significant component of the recycling process is the production of automotive
shredder residue (ASR). This is currently landfilled across Europe. The
additional 10% could be met by processing ASR through either waste-to-energy
facilities or Post shredder technology (PST) to recover materials. The UK auto
and recycling sectors claimed there would need to be a massive investment by
their members in both new capacity and new technology for PST to recover
additional recycle materials. It has been shown that 50% of the ASR contains
valuable recoverable materials which could be used to meet the Directive target.
It is expected in the next 5years that technological innovation in car design
will change the composition from easily recoverable metal to difficult polymers.
This change in composition will impact on the current drive to integrate the
European Circular Economy Package. A positive factor is that main driver for
using ASR is coming from the metals recycling industry itself. They are looking
to develop the infrastructure for energy generation from ASR and subsequent
material recovery. This is driven by the economics of the process rather than
meeting the Directive targets. The study undertaken has identified potential
pathways and barriers for commercial thermal treatment of ASR. The results of ASR
characterisation were used to assess commercial plants from around the world.
Whilst there were many claiming that processing of ASR was possible none have so
far shown both the technological capability and economic justification.
PMID- 28501265
TI - An algorithm for the management of coagulopathy from postpartum hemorrhage, using
fibrinogen concentrate as first-line therapy.
AB - BACKGROUND: We constructed an algorithm for the management of coagulopathy from
massive postpartum hemorrhage. Fibrinogen concentrate was administered
preferentially, and the dose of both fibrinogen concentrate and fresh frozen
plasma given was determined by the plasma fibrinogen concentration and
prothrombin time. The efficacy of the algorithm and the amount of fibrinogen
concentrate and fresh frozen plasma transfused were determined. METHODS: The
study was conducted in a single teaching perinatal center. Nineteen patients were
included between April 2011 and March 2014 (patient group). For a historical
comparison group, we retrospectively analyzed the records of 19 patients who had
been treated for coagulopathy from massive postpartum hemorrhage between April
2006 and March 2011 (control group). RESULTS: Blood loss was significantly lower
in the patient group. No adverse events were associated with this management in
either group. The dose of fibrinogen concentrate administered was significantly
higher and that of fresh frozen plasma administered was significantly lower in
the patient group. CONCLUSION: This algorithm appeared to help reduce blood loss
and the total amount of fresh frozen plasma transfused when treating coagulopathy
from postpartum hemorrhage, and may represent another strategy for achieving
hemostasis in this setting.
PMID- 28501266
TI - Cochleotoxicity monitoring protocol.
AB - INTRODUCTION: Cochlear damage is frequent in long-term aminoglycosides therapy or
chemotherapeutic treatments with platinum-based agents. Despite its prevalence,
it is currently underestimated and underdiagnosed. A monitoring protocol is vital
to the early detection of cochleotoxicity and its implementation is widely
encouraged in every hospital unit. Our aim was to elaborate a cochleotoxicity
monitoring protocol for patients treated with platinum compounds or
aminoglycosides antibiotics. METHODS: PubMed(r) database was searched using terms
relevant to drug cochleotoxicity in order to identify the most adequate protocol.
Several articles and guidelines influenced our decision. RESULTS: There is no
consensus on a universal monitoring protocol. Its formulation and application
rely heavily on available resources and personnel. High-frequency audiometry and
otoacoustic emissions play an important role on early detection of
cochleotoxicity caused by aminoglycoside antibiotics and platinum compounds.
CONCLUSION: A cochleotoxicity monitoring protocol consisting on an initial
evaluation, treatment follow-up and post-treatment evaluation is proposed.
PMID- 28501267
TI - Gender equity imbalance in electrocardiology: A call to action.
AB - Despite the increasing number of women entering the medical profession, senior
positions and academic productivity in many fields of medicine remain to be men
dominated. We explored gender equity in electrocardiology as perceived by recent
academic productivity and also active participation (presidencies and board
constituents) in both the International Society of Electrocardiology (ISE) and
the International Society for Holter and Noninvasive Electrocardiology (ISHNE).
Academic productivity was measured by authorship (first and senior) in the
Journal of Electrocardiology (JECG) and the Annals of Noninvasive
Electrocardiology (ANE) in 2015. The percentage of women ISE and ISHNE Presidents
was 5.6% and 0%, respectively. Current women board constituents for each society
was 12.1% for ISE, and 9.4% for ISHNE. JECG articles published in 2015 had
considerably less women compared to men for both senior (16.3%) and first (25.3%)
authorship. ANE articles published in 2015 followed the same trends in gender,
having less women compared to men for both senior (9.4%) and first (19.3%)
authorship. There is a gender equity imbalance in the field of Electrocardiology.
Identifying a gender imbalance is important for understanding reasons behind
these trends, and may also help improve gender equity in Electrocardiology.
PMID- 28501268
TI - Techniques to Form a Suitable Lipiodol-Epirubicin Emulsion by Using 3-Way
Stopcock Methods in Transarterial Chemoembolization for Liver Tumor.
AB - PURPOSE: To compare physicochemical properties of emulsions of ethiodized oil
(Lipiodol; Guerbet, Villepinte, France) and epirubicin prepared using different
techniques for conventional transarterial chemoembolization. MATERIALS AND
METHODS: Lipiodol was mixed with epirubicin solution (8.33 mg/mL) by using a 3
way stopcock. The following technical parameters were compared: ratio of
epirubicin solution to Lipiodol (1:2 vs 1:1), number of pumping exchanges through
the stopcock (20 exchanges vs 10 exchanges), pumping speed (1 s/push vs 2
s/push), and first push syringe (epirubicin solution vs Lipiodol). RESULTS: The
mean percentage of water-in-oil was 70.45 +/- 1.51 in the 1:2 epirubicin-Lipiodol
ratio and 16.03 +/- 2.95 in the 1:1 ratio (P < .001). The first push syringe did
not influence emulsion type. Median droplet sizes were significantly larger in
the slower pumping speed (52.0 MUm in 2 s vs 33.7 MUm in 1 s; P < .001), whereas
there was no significant difference in number of pumping exchanges. Droplet sizes
enlarged during 30 minutes after pumping. Viscosity was lower in the 1:1 ratio
and the slower pumping speed. Viscosity decreased during 30 minutes after
pumping. CONCLUSIONS: The ratio of epirubicin to Lipiodol is a significant factor
to form water-in-oil emulsions with higher viscosity. The percentage of water-in
oil is limited to 70% using current pumping techniques. The pumping speed
strongly influences droplet size and viscosity.
PMID- 28501270
TI - A novel stereotactic frame for real PET-guided biopsies: A preclinical proof-of
concept.
AB - PURPOSE: To design, build and test a stereotactic device that allows PET image
guided biopsies to be performed. METHODS: An initial prototype consisting of four
main pieces, one of which contains radioactive markers to make it visible in the
PET images, was built using a 3D printer. Once the device is mounted, a spherical
coordinate system is built with the entrance needle point in the skin as the
origin of coordinates. Two in-house software programs, namely getCoord.ijm, which
obtains the spherical coordinates of the tumour tissue to be biopsied, and
getNeedle.ijm, which virtualizes the inner needle tip once the puncture has taken
place, were written. This prototype was tested on an FDG-doped phantom to
characterize both the accuracy of the system and the procedure time. RESULTS: Up
to 11 complete biopsy procedures were conducted. The mean total procedure time
was less than 20min, which is less than the procedure time of conventional
standard CT-guided biopsies. The overall accuracy of the system was found to be
5.0+/-1.3mm, which outperforms the criterion used in routine clinical practice
when targeting tumours with a diameter of 10mm. CONCLUSIONS: A stereotactic frame
to conduct real PET image-guided biopsies has been designed and built. A proof-of
concept was performed to characterize the system. The procedure time and accuracy
of the system were found to meet the current needs of physicians performing
biopsies.
PMID- 28501269
TI - Peak enhancement ratio of myocardium to aorta for identification of myocardial
ischemia using dynamic myocardial computed tomography perfusion imaging.
AB - BACKGROUND: This study aimed to evaluate the feasibility of peak enhancement (PE)
ratio of myocardium to aorta (PER) derived from stress dynamic computed
tomography myocardial perfusion imaging (CTP) for the detection of myocardial
ischemia assessed by magnetic resonance (MR) imaging. METHODS: Forty-four
patients who underwent stress dynamic CTP and MR imaging were retrospectively
evaluated. From the time-attenuation curve, myocardial PE, PER, and myocardial
blood flow (MBF) were calculated on a segment-based analysis. The correlation
between myocardial and aortic PE was assessed by Spearman's correlation, and the
differences in myocardial PE and PER between normal and ischemic myocardium were
assessed by the Mann-Whitney U-test. The diagnostic accuracies of myocardial PE,
PER, and MBF for detecting myocardial ischemia were compared by receiver
operating characteristic analysis. RESULTS: Of 704 segments, 258 segments (37%)
were diagnosed as myocardial ischemia with MR imaging. Myocardial and aortic PE
were significantly correlated in both normal and ischemic segments (r=0.76 and
0.58; p<0.05, in each). The myocardial PE and PER of ischemic segments were
significantly lower than those of normal segments (p<0.05, in each). Sensitivity
and specificity were 61% [95% confidence interval (CI), 55-70%] and 83% (95% CI,
73-87%) for myocardial PE, 78% (67-88%) and 82% (95% CI, 70-91%) for PER, and 81%
(95% CI, 73-87%) and 85% (95% CI, 79-92%) for MBF. There was a significantly
larger area under the curve for PER (0.87; 95% CI, 0.84-0.90) and MBF (0.88;
95%CI, 0.85-0.91), compared to myocardial PE (0.75; 95% CI, 0.70-0.79) (p<0.05,
in each). There was no significant difference in area under the curve between PER
and MBF. CONCLUSIONS: The semi-quantitative parameter of PER showed a high
diagnostic accuracy for the detection of myocardial ischemia, comparable to that
of MBF.
PMID- 28501271
TI - Virtual cystoscopy, computed tomography urography and optical cystoscopy for the
detection and follow-up for bladder cancer.
AB - OBJECTIVES: To evaluate the utility of virtual cystoscopy (VC) performed with CT
urography in patients being studied under gross hematuria or patients being
followed-up after a previous bladder cancer and compare the results with those
obtained with gold standard technique (optical cystoscopy). METHODS:
Retrospective study of 117 patients who were referred for VC by the Urology
Department between May 2014 and May 2015. Those patients presented with gross
hematuria or they were previously treated patients from bladder cancer being
followed up. These patients were evaluated with MDCT and virtual cystoscopy after
distending the bladder with air. The results were compared with those obtained
with optical cystoscopy which was performed no more than a week after. RESULTS:
The global sensitivity and specificity of VC were 81,8 and 92,1%. Aditional
findings detected in CT urography were an aortic dissection, urinary lithiasis
and colonic metastasis. CONCLUSION: VC seems an useful technique in the diagnosis
and follow-up for bladder cancer with a good correlation with OC. The main
limitations are the impossibility of biopsy during the procedure and the
detection of erythematous lesions. Collateral findings can be detected performed
with CT urography although the high radiation exposure does not recommend their
combined use.
PMID- 28501272
TI - Oxidative stress in pre-eclampsia; have we been looking in the wrong place?
PMID- 28501273
TI - Cerebral white matter lesions after pre-eclampsia.
AB - BACKGROUND: Women who have had pre-eclampsia in their previous pregnancies
demonstrate a greater prevalence of cerebral white matter lesions several years
after the pregnancy than women who have been normotensive during their pregnancy.
Both the pathophysiology and the timing of development of these lesions are
uncertain. White matter lesions, in the general population, are associated with
an increased risk of stroke, dementia and death. AIMS AND OBJECTIVES: The
objective of the study was to determine the prevalence of cerebral white matter
lesions amongst women with severe pre-eclampsia at delivery, 6months and 1year
postpartum and to establish the possible pathophysiology and risks factors.
METHODS: This was a longitudinal study performed at Steve Biko Academic Hospital,
a tertiary referral hospital in Pretoria South Africa. Ninety-four women with
severe pre-eclampsia were identified and recruited during the delivery admission.
Magnetic resonance imaging (MRI) of the brain was performed post - delivery and
at 6months and 1year postpartum. RESULTS: Cerebral white matter lesions were
demonstrated in 61.7% of women at delivery, 56.4% at 6months and 47.9% at 1year.
Majority of the lesions were found in the frontal lobes of the brain. The
presence of lesions at 1year post-delivery was associated with the number of
drugs needed to control blood pressure during pregnancy (OR 5.1, 95% CI 2.3-11.3,
p<0.001). The prevalence of WMLs at 1year was double in women with chronic
hypertension at 1year compared to those women who were normotensive (65.1% vs
32.3%). CONCLUSION: Women who require 2 or more drugs to control blood pressure
during pregnancy have an increased risk of developing cerebral white matter
lesions after delivery.
PMID- 28501274
TI - Impact of fetal growth on pregnancy outcomes in women with severe preeclampsia.
AB - OBJECTIVE: To estimate whether pregnancy outcomes in women with severe
preeclampsia (sPE) with small for gestational age (SGA) fetuses differ from those
with sPE without SGA or isolated SGA. STUDY DESIGN: We conducted a retrospective
cohort study of consecutive non-anomalous, livebirths in a single tertiary care
institution from 2004 to 2008. We compared pregnancy outcomes in women who had
sPE with SGA (birthweight<10th percentile), and sPE without SGA to those with
isolated SGA as reference. The primary outcome was a neonatal composite score
including low 5-min APGAR, NICU admission and neonatal death. Secondary outcomes
were components of the composite as well as placental abruption and cesarean
delivery. Analysis was repeated with SGA defined as birthweight<5th percentile.
Multivariable logistic regression was used to adjust for confounders. RESULTS:
1905 women met inclusion criteria: 156 sPE with SGA, 746 sPE without SGA, 1003
isolated SGA. The risk of the neonatal composite score was higher for sPE with
SGA (adjusted odds ratio [aOR] 2.29; 95% confidence interval [CI] 1.39-3.79) and
sPE without SGA (aOR 3.66; 95% CI 2.71-4.93) compared to isolated SGA. The risk
of abruption and cesarean were similarly increased in women with sPE with SGA and
sPE without SGA compared to those with isolated SGA. CONCLUSION: Similar to women
with sPE without SGA fetus, women who have sPE with SGA are at a higher risk for
several adverse maternal and neonatal outcomes compared to isolated SGA. These
findings suggest that women with preeclampsia and SGA should be managed as sPE
rather than as isolated SGA.
PMID- 28501275
TI - Dysregulation of the Fas/FasL system in an experimental animal model of HELLP
syndrome.
AB - INTRODUCTION: Placental FasL is up-regulated in women with HELLP (hemolysis
elevated liver enzyme and low platelet) syndrome and has been proposed to
contribute to the liver damage seen in these patients. OBJECTIVE: This study
aimed to determine if an experimental rodent model of HELLP also had
dysregulation of Fas/FasL compared to normal pregnant (NP) rats. We also set out
to determine if blockade of the endothelin system regulated Fas/FasL expression
in HELLP rats. STUDY DESIGN: On gestational day (GD) 12, sEng (7ug/kg) and sFlt-1
(4.7ug/kg) infusion began via mini-osmotic pump into NP rats. On GD19 plasma and
tissue were collected and FasL and Fas were measured via enzyme linked
immunosorbent assay and gene expression via real-time PCR. RESULTS: HELLP rats
had significantly more circulating and placental FasL compared to NP rats,
whereas hepatic FasL was decreased and placental Fas was increased compared to NP
rats. Administration of an endothelin A receptor antagonist (ETA) beginning on
GD12 significantly decreased placental expression of Fas in HELLP rats. Liver
mRNA transcript of Fas was significantly increased in HELLP rats compared to NP
rats. CONCLUSION: These data suggest that rats in this experimental model of
HELLP syndrome have abnormal expression of the Fas/FasL system. Future studies
will examine the sources of Fas/FasL dysregulation in this model and if blockade
could reduce some of the inflammation and hypertension associated with HELLP
syndrome.
PMID- 28501276
TI - Diagnosis of preeclampsia and fetal growth restriction with the sFlt-1/PlGF
ratio: Diagnostic accuracy of the automated immunoassay Kryptor(r).
AB - OBJECTIVE: We aimed to characterize the diagnostic accuracy of the Kryptor(r)
assay for sFlt-1 and PlGF in maternal serum samples of uneventful singleton
pregnancies and subjects with preeclampsia (PE) and PE-related outcomes such as
fetal growth restriction (FGR). Longitudinal reference ranges of the sFlt-1 and
PlGF level in the course of normal pregnancies were generated. METHODS: A cohort
of subjects with PE and PE-related outcomes including FGR in the third trimester
was compared to a cohort of women with uneventful outcome. Serum levels of sFlt
1, PlGF level as well as the sFlt-1/PlGF ratio was analysed with the Kryptor(r)
assay and compared between the case- and control groups. Cut-off values were
generated and diagnostic accuracy examined. RESULTS: Longitudinal reference
ranges of the sFlt-1 and PlGF level in healthy pregnancies were in line with
those levels measured with other immunoassays. Comparison of the sFlt-1/PlGF
ratio between PE-related outcomes including FGR or PE and healthy controls showed
a high diagnostic accuracy with an area under the curve (AUC) of 0.917 for PE
related outcomes and 0.919 for PE.
PMID- 28501277
TI - Inherited predisposition to preeclampsia: Analysis of the Aberdeen
intergenerational cohort.
AB - OBJECTIVE: To assess the magnitude of familial risk of preeclampsia and
gestational hypertension in women born of a preeclamptic pregnancy and those born
of pregnancy complicated by gestational hypertension while accounting for other
risk factors. METHODS: An intergenerational dataset was extracted from the
Aberdeen Maternity and Neonatal Databank (AMND) which records all pregnancy and
delivery details occurring in Aberdeen, Scotland since 1950. The analysis
included all nulliparous women whose mothers' records at their births are also
recorded in the AMND. Multinomial logistic regression was used to assess the risk
of having preeclampsia or gestational hypertension based on maternal history of
preeclampsia or gestational hypertension. RESULTS: There were 17302 nulliparous
women included, of whom 1057(6.1%) had preeclampsia while 4098(23.7%) had
gestational hypertension. Furthermore, 424(2.5%) and 2940(17.0%) had maternal
history of preeclampsia and gestational hypertension respectively. The risk of
preeclampsia was higher in women who were born of pregnancies complicated by
preeclampsia (adjusted RRR 2.55 95% CI 1.87-3.47). This was higher than the risk
observed in women whose mothers had gestational hypertension (adjusted RRR 1.44
95% CI 1.23-1.69). Conversely, the risk of gestational hypertension was similar
in those who were born of preeclamptic pregnancies (adjusted RRR 1.37 95% CI 1.09
1.71) and those whose mothers had gestational hypertension (adjusted RRR 1.36 95%
CI 1.24-1.49). CONCLUSION: There was a dose response effect in the inheritance
pattern of preeclampsia with the highest risk in women born of preeclamptic
pregnancies. Gestational hypertension showed similar increased risk with maternal
gestational hypertension and preeclampsia.
PMID- 28501278
TI - Antenatal risk factors associated with need of postpartum antihypertensives in
women with preeclampsia in South India: Case control study.
AB - OBJECTIVES: To investigate the antepartum risk factors associated with the need
for antihypertensive medication in the postpartum period in women with pre
eclampsia. METHODOLOGY: Matched retrospective case control study was done in a
tertiary center in south India between January 2016 and June 2016. We compared
100 preeclamptic women requiring antihypertensive medication in the postpartum
period at discharge with 100 preeclamptic women who were not on antihypertensive
medication at discharge, matched for age and parity at a ratio 1:1. Demographic
data, maternal medical conditions, and delivery data were abstracted from
maternal charts. Risk factors were evaluated using conditional logistic
regression. RESULTS: Gestational age at delivery was comparable in both groups
(34.3vs. 35.6weeks, p=0.220). Cesarean section rates were higher in the cases
compared to controls (53% vs. 32%, p=0.004). After adjusting for age and parity
women who had eclampsia, required prophylactic magnesium sulphate therapy and
high peak antenatal systolic blood pressure were associated with postpartum
antihypertensives. Using multivariate conditional logistic regression, mean
systolic blood pressure (OR=1.03, 95% CI 1.00-1.07), development of eclampsia
(OR=6.43, 95% CI 1.03-39.91) and need of prophylactic magnesium sulphate
(OR=5.02, 95% CI 2.02-12.47) were found to be associated with the need of
postpartum antihypertensives. CONCLUSIONS: In women with preeclampsia,
development of eclampsia, use of prophylactic magnesium sulphate and high peak
antenatal systolic blood pressure are more likely to require antihypertensives in
postpartum period.
PMID- 28501280
TI - Evaluation of placental vascularization by three-dimensional ultrasound
examination in second and third trimester of pregnancies complicated by chronic
hypertension, gestational hypertension or pre-eclampsia.
AB - OBJECTIVES: The purpose of this study was to assess three-dimensional placental
power Doppler indices in second and third trimester of pregnancies complicated by
chronic-, gestational hypertension or pre-eclampsia. METHODS: We analyzed 226
pregnancies prospectively measuring three-dimensional placental power Doppler
indices (vascularization index, flow index, vascularization flow index) in cases
of normal blood pressure (N=109), chronic hypertension (N=43), gestational
hypertension (N=57) and pre-eclampsia (N=17). We evaluated the correlation among
vascularization indices, flow characteristics of uterine arteries and perinatal
outcome. We assessed the influence of maternal factors (pregestational body mass
index, previous pregnancies/deliveries, maternal age) on vascularization indices,
and analyzed histological findings of placenta from pregnancy hypertension
groups. RESULTS: Vascularization index was significantly higher (p=0.010) in
pregnancies with chronic- and lower (p=0.152) in pregnancies with gestational
hypertension and preeclampsia compared to the normal group. Flow index was
significantly lower in all three pathological groups compared to normal group.
Placental volume was significantly smaller (p<0.001) in all three pathological
groups than in normal pregnancies at the time of delivery, and there was no
significant difference between the three affected groups. The rate of adverse
pregnancy outcomes showed no significant difference between the normal and
chronic hypertension groups. We observed significantly lower 1', 5' and 10' APGAR
scores (p<0.,001), and birth weight in preeclampsia compared to chronic-,
gestational hypertension, and normal groups. Maternal factors had no influence on
the development of the power Doppler indices. CONCLUSION: Vascularization indices
seem good markers for the prediction of risks and adverse outcomes in case of
pregnancy hypertension.
PMID- 28501279
TI - Clinical and laboratory markers in the recovery from severe preeclampsia.
AB - OBJECTIVE: To examine the recovery from severe Preeclampsia toxemia (PET) in
women treated with magnesium sulfate (MgSO4) during the first 24h postpartum as
reflected by the changes in various clinical and laboratory markers. STUDY
DESIGN: The study population included all women diagnosed with severe PET that
gave birth at the Soroka University Medical center between 2013 and 2014, and
were treated with MgSO4 in the first 24h postpartum. Data were collected from the
institutional computerized records. The different parameters were examined in 6h
intervals and were compared using appropriate statistical tests. MAIN OUTCOMES
MEASURES: Change in various postpartum laboratory and clinical parameters.
RESULTS: During the study period there were 132 singleton deliveries with severe
PET treated with a 24-hours postpartum MgSO4 regimen. Most of the women were
primigravida and delivered vaginally. Both mean systolic and mean diastolic blood
pressure values have shown recovery to normal values after the first 6h of
treatment (P<0.001). Urine output and proteinuria have demonstrated later
recovery (after 12h). CONCLUSIONS: When assessing the natural recovery of severe
PET features, the earliest parameter to recover during the first 24h postpartum
is hypertension followed by urine output and the proteinuria. Further larger
studies are needed in order to confirm these results. Moreover, the use of these
parameters may allow using shorter MgSO4 treatment regimens for appropriate women
showing earlier recovery and facilitating quicker mother-baby bonding and
emotional recovery.
PMID- 28501281
TI - Alteration of serum adropin level in preeclampsia.
AB - To clarify the alterations in serum adropin and preptin concentrations in
preeclampsia, we determined serum adropin and preptin levels in 29 women with
normal pregnancy and 32 women with preeclampsia. We found that maternal age, body
mass index and fetal gender were not significantly different between two groups;
however, blood pressure, gestational age and neonatal birth weight were
significantly different. Serum adropin levels were significantly increased in
women with preeclampsia compared with those with normal pregnancy but there were
no significant differences in preptin levels. An increase in maternal serum
adropin level was found in preeclampsia, and this may be a compensation for
pregnancy complicated with preeclampsia.
PMID- 28501282
TI - Proteinuria in preeclampsia: Not essential to diagnosis but related to disease
severity and fetal outcomes.
AB - Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality
globally and proteinuria can be one of the cardinal features of this disease.
However, studies about the association of the amount of proteinuria and the
severity of preeclampsia, and perinatal outcomes are limited. Data on 239 women
with preeclampsia were retrospectively collected from a university teaching
hospital from September 2011 to June 2013 and analysed. Data included all
clinical parameters and proteinuria in a 24h urine collection. In cases of severe
preeclampsia, significantly fewer patients had proteinuria levels <0.3g/L in
comparison to any of the other groups with proteinuria >0.3g/L, but there was no
difference in cases of severe preeclampsia when proteinuria levels were >0.3g/L.
Furthermore, when proteinuria levels were >0.3g/L, the frequency of severe
preeclampsia in each group was significantly higher than the frequency of mild
pre-eclampsia cases. Time of onset was significantly earlier in patients with
proteinuria >3g/L in a 24h urine collection, but time between the onset of
preeclampsia and delivery was not correlated with the amount of proteinuria. The
birth weight was significantly lower in patients with proteinuria >3g/L. The
incidence of fetal growth restriction or stillbirth was significantly higher in
patients with proteinuria >5g/L. Our data demonstrate that the amount of
proteinuria is not associated with the severe of preeclampsia, once proteinuria
is detected, but is related to the severity of preeclampsia. The adverse fetal
outcomes appear to be the function of prematurity rather than proteinuria itself.
PMID- 28501283
TI - Assessment of annexin A5 and annexin A2 levels as biomarkers for pre-eclampsia: A
pilot study.
AB - Deficient anticoagulant activity of annexin A5 and deficient profibrinolytic
activity of annexin A2 have been linked to increased risk of thrombotic events.
Placental dysfunction due to fibrin deposition/microthrombi has been implicated
in the pathogenesis of pre-eclampsia (PE). In this study, we aimed to assess
serum levels of annexin A5 and annexin A2 in a cohort of PE patients and
investigate their role as biomarkers for the development of the disease. We
examined 80 women in total; 40 healthy pregnant women and 40 pregnant women with
PE after 20weeks of pregnancy. Women were subjected to full clinical assessment,
ultrasonography, and laboratory testing including complete blood picture, liver
and kidney function tests and assessment of serum and urine proteins. Annexin A5
and annexin A2 were analyzed using enzyme-linked immunosorbent assay. The study
showed serum annexin A2 but not annexin A5 was significantly reduced (P=0.029) in
women with PE (total and severe cases) compared to those with normal pregnancy.
The ROC analysis of annexin A2 level for the prediction of development of PE
showed an area under the curve of 0.64 (P=0.029), and the best cut-off value was
0.89ng/ml with a sensitivity of 70.0% and a specificity of 70.0%. Univariate
analysis showed annexin A2 of <0.89ng/ml, proteinuria, lower platelet count and
higher BP were associated with significantly higher risk to develop PE. Based on
this pilot study, serum annexin A2 levels may be a useful biomarker for pre
eclampsia. However, a larger study is required before a final conclusion is made.
PMID- 28501284
TI - Reliability of home blood pressure monitoring devices in pregnancy.
AB - Home blood pressure monitors are freely available and used for women during
pregnancy. The exact role of home blood pressure monitoring in pregnancy remains
uncertain, and few such monitors have been validated for use in pregnancy. As it
has been our Unit's policy to test these devices against sphygmomanometry (as the
gold standard) before clinical use for some years now, we undertook this study to
ascertain the degree of accuracy or inaccuracy of these devices in usual clinical
practice. We analysed 9 consecutive blood pressures (BP) alternately using an
automated home BP device and sphygmomanometry in 127 pregnant women with
hypertension using two different methods: a) a modified version of the British
Hypertension Society's guidelines for analysing automated devices, and b)
examining the difference between the mean of blood pressure readings by the
device and sphygmomanometry for each patient. 87 devices (69%) had systolic BP
within 5mmHg or less and 98 (77%) were within 5mmHg for diastolic BP. The
frequency of systolic BPs within 5mmHg was similar for non-validated vs.
validated devices (75vs. 60%; p=0.23). Similarly, diastolic BP within 5mmHg was
similar for non-validated vs. validated devices (86vs. 68%, p=0.06). Our findings
showed that a wide variety of devices are used and few if any have been formally
validated for use in pregnancy. As a group the devices provide accurate BP in the
majority of women, but up to a quarter will have a BP difference of at least
5mmHg, and this is not related to the absolute BP. Furthermore using a home BP
device validated for general use in non-pregnant subjects appeared as reliable as
using other non-validated devices. On the basis of these data we recommended
clinicians always perform their own analysis of a patient's home BP machine
accuracy prior to home use using a simple protocol as described here, even if the
machine has been validated for general use.
PMID- 28501285
TI - Construct validity of a novel, objective evaluation tool for the basics of open
laparotomy training using a simulated model.
AB - BACKGROUND: We describe initial success in designing and implementing an
objective evaluation for opening and closing a simulated abdomen. METHODS: (1) An
assessment for laparotomy was created using peer-reviewed literature, texts, and
the input of academic surgeons nationally; (2) the assessment was evaluated for
construct validity, comparing the videotaped performance of laparotomy by
surgical experts and novices on a viscoelastic model; and (3) the basics of open
laparotomy training (BOLT) curriculum was piloted with junior residents to
evaluate efficacy at improving performance. RESULTS: Experts performed better
than novices opening (.94 vs .51; P < .001), closing (.85 vs .16; P < .001), and
overall performance (.88 vs .27; P < .001). Novices caused bowel injury more
frequently (5 vs 1; P < .05) and took longer to open the abdomen (6:06 vs 3:43; P
= .01). After completing the BOLT curriculum, novices improved for opening (1.00
vs .50; P = .014), closing (.80 vs .10; P = .014), and overall score (.87 vs .23;
P = .014). CONCLUSIONS: We demonstrate construct validity of an evaluation tool
for simulated laparotomy, and pilot efforts with the BOLT curriculum have shown
promise.
PMID- 28501286
TI - The correlation between stabbing-related upper extremity wounds and survival of
stabbing victims with abdominal and thoracic injuries.
AB - BACKGROUND: When treating patients with stab injuries of the torso, clinicians
often lack timely information about the degree and nature of internal organ
damage. An externally observable sign significantly associated with
characteristics of torso injuries may therefore be useful for practitioners. One
such potential sign is the presence of wounds to the hands, sometimes sustained
during victims' attempt to defend themselves during the violent altercation.
Thus, the primary aim of this study was to evaluate the association between
presence of upper extremity wounds and the severity of the thoracic and intra
abdominal injuries due to stabbing. METHODS: This study was carried out
retrospectively using data on 8714 patients with stabbing-related injuries from
19 trauma centers that participated in the Israeli National Trauma Registry
(INTR) between January 1st1997 and December 31st 2013. Patients with wounds of
upper extremities in addition to torso injuries (UE group) were compared to other
patients with torso injuries (TO group) in terms of demographics, injury
characteristics and clinical outcome. RESULTS: The compared groups were found to
be homogeneous in terms of age and systolic blood pressure; the number of
sustained torso injuries was also identical. The UE group comprised a slightly
greater percentage of females, however both groups were predominantly male.
Patients with upper extremity injuries had a lower proportion of internal organ
damage (36% vs. 38.5%) and lower mortality (0.9% vs. 2%). The higher mortality of
patients without upper extremity wounds remained significantly different even
when adjusted by other epidemiological parameters (OR 2.46, 95% CI 1.33-5.08).The
number of sustained upper extremity injuries was positively associated with
deeper penetration of the torso by the stabbing instrument. CONCLUSIONS: Patients
with stabbing-related upper extremity wounds had a significant survival advantage
over patients without such injuries. However, a greater number of sustained upper
extremity wounds may be an external sign of greater severity of thoracic and
intraabdominal stabbing injuries.
PMID- 28501287
TI - Femoral nerve block in a representative sample of elderly people with hip
fracture: A randomised controlled trial.
AB - INTRODUCTION: The number of elderly people with hip fracture and dementia is
increasing, and many of these patients suffer from pain. Opioids are difficult to
adjust and side effects are common, especially with increased age and among
patients with dementia. Preoperative femoral nerve block is an alternative pain
treatment. AIM: To investigate whether preoperative femoral nerve block reduced
acute pain and opioid use after hip fracture among elderly patients, including
those with dementia. PATIENTS AND METHODS: In this randomised controlled trial
involving patients aged >=70years with hip fracture (trochanteric and cervical),
including those with dementia, we compared femoral nerve block with conventional
pain management, with opioid use if required. The primary outcome was
preoperative pain, measured at five timepoints using a visual analogue scale
(VAS). Preoperative opioid consumption was also registered. RESULTS: The study
sample comprised 266 patients admitted consecutively to the Orthopaedic Ward. The
mean age was 84.1 (+/-6.9)years, 64% of participants were women, 44% lived in
residential care facilities, and 120 (45.1%) had dementia diagnoses. Patients
receiving femoral nerve block had significantly lower self-rated pain scores from
baseline to 12h after admission than did controls. Self-rated and proxy VAS pain
scores decreased significantly in these patients from baseline to 12h compared
with controls (p<0.001 and p=0.003, respectively). Patients receiving femoral
nerve block required less opioids than did controls, overall (2.3+/-4.0 vs. 5.7+/
5.2mg, p<0.001) and in the subgroup with dementia (2.1+/-3.3 vs. 5.8+/-5.0mg,
p<0.001). CONCLUSION: Patients with hip fracture, including those with dementia,
who received femoral nerve block had lower pain scores and required less opioids
before surgery compared with those receiving conventional pain management.
Femoral nerve block seems to be a feasible pain treatment for elderly people,
including those with dementia.
PMID- 28501288
TI - Recurrent Episodes of Brief Global Amnesia Related to Intrathecal Baclofen Pump:
Originally Mistaken for Psychogenic Nonepileptic Seizures.
PMID- 28501289
TI - Alcohol-Related Dementia: A Systemic Review of Epidemiological Studies.
AB - BACKGROUND: Alcohol-related dementia (ARD) is a heterogeneous long-term cognitive
problem that can develop in the course of alcoholism. Current understanding of
ARD remains limited. METHODS: We conducted a systematic review to synthesize
available data on the epidemiology of ARD, through searching the relevant studies
in the PubMed, PsycINFO, and ALOIS. "Alcohol" and "dementia" were used as
keywords. RESULTS: We included articles published between January 1, 1991 and
February 29, 2016, where language was not limited. Of the 9 identified articles,
the prevalence of ARD ranged from 1.19/1000 in multiday admission patients
residing in the United Kingdom to 25.6% in elderly clinic alcoholics from the
United States. The proportion of ARD in early-onset dementia taken from 3 studies
was approximately 10%, whereas only 1.28% in late-onset dementia taken from 1
study. CONCLUSIONS: Considering the relatively high proportion of ARD in early
onset dementia and its potentially reversible course, future investigation into
ARD is necessary.
PMID- 28501290
TI - Use of Transdermal Selegiline in Pregnancy and Lactation: A Case Report.
PMID- 28501291
TI - Use and dependence on opioid drugs in the Spanish population with chronic pain:
Prevalence and differences according to sex.
AB - OBJECTIVES: To analyse the prevalence in the use and dependence on opioid drugs
in the Spanish population with chronic pain and evaluate the differences
according to sex. PATIENTS AND METHODS: The demographic variables, opioid
treatment characteristics and use of other substances were assessed in 229 users
of opioid drugs. A descriptive bivariate analysis of the data was performed.
RESULTS: Forty-six percent of the patients met the criteria of dependence on
opioid drugs (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition
[DSM-IV-TR]). Alcohol and cannabis consumption was greater in the men. The rates
of dependence on the use of opioid drugs were significantly higher in the
extended treatments. CONCLUSIONS: Planning for treatments with opioids and
strategies for preventing inappropriate use should not depend on the patient's
sex. We need further studies on the medical and psychological variables related
to the use of and dependence on opioids.
PMID- 28501292
TI - Gender Differences in Medicine-From Medical School to Medicare.
PMID- 28501293
TI - Gender Differences in Physician Service Provision Using Medicare Claims Data.
AB - OBJECTIVE: To determine differences in the provision of Medicare services based
on physician gender in the United States. PATIENTS AND METHODS: Participants
included all 2013 Medicare fee-for-service physicians and their patients, a
population that is predominantly older than 65 years. The 2013 Medicare Provider
Utilization and Payment Data for services rendered between January 1, 2013, and
December 31, 2013, were combined with the 2015 Physician Compare National
Downloadable files and 2015 Berenson-Eggers Type of Service classification files.
Total fee-for-service Medicare payments and Healthcare Common Procedure Coding
System procedure codes for all fee-for-service beneficiaries were aggregated
according to physician gender, specialty, years since medical school graduation,
and type of service classifications. RESULTS: Excluding drug reimbursement, the
mean total Medicare payments per female physician, compared with those for male
physicians, were 41% in surgical specialties, 72% in hospital-based specialties,
and 55% across all specialties (P<.001). The mean overall number of unique
beneficiary visits per female physician was 59% of that for male physicians
(P<.001). By using the Berenson-Eggers Type of Service classification, procedures
and other services by female physicians were of 54% lower overall average
intensity (allowed payments/number of unique patients) compared with those of
male physicians. These differences persisted irrespective of years since medical
school graduation (P<.001). CONCLUSION: Female physicians had smaller average
total Medicare payments and fewer unique beneficiary visits than male physicians
in the care of fee-for-service Medicare beneficiaries in 2013. The differences
persisted across specialty types and years in practice. These data can identify
variation but cannot determine causation or explain the reasons behind gender
differences. These findings suggest, but do not prove, that female physician
Medicare payments are lower due to different practice patterns, consisting of
fewer patients cared for and lower intensity of care.
PMID- 28501294
TI - Cognitive endpoints for therapy development for neuronopathic
mucopolysaccharidoses: Results of a consensus procedure.
AB - The design and conduct of clinical studies to evaluate the effects of novel
therapies on central nervous system manifestations in children with neuronopathic
mucopolysaccharidoses is challenging. Owing to the rarity of these disorders,
multinational studies are often needed to recruit enough patients to provide
meaningful data and statistical power. This can make the consistent collection of
reliable data across study sites difficult. To address these challenges, an
International MPS Consensus Conference for Cognitive Endpoints was convened to
discuss approaches for evaluating cognitive and adaptive function in patients
with mucopolysaccharidoses. The goal was to develop a consensus on best practice
for the design and conduct of clinical studies investigating novel therapies for
these conditions, with particular focus on the most appropriate outcome measures
for cognitive function and adaptive behavior. The outcomes from the consensus
panel discussion are reported here.
PMID- 28501295
TI - Discovering DNA methylation patterns for long non-coding RNAs associated with
cancer subtypes.
AB - Despite growing evidence demonstrates that the long non-coding ribonucleic acids
(lncRNAs) are critical modulators for cancers, the knowledge about the DNA
methylation patterns of lncRNAs is quite limited. We develop a systematic
analysis pipeline to discover DNA methylation patterns for lncRNAs across
multiple cancer subtypes from probe, gene and network levels. By using The Cancer
Genome Atlas (TCGA) breast cancer methylation data, the pipeline discovers
various DNA methylation patterns for lncRNAs across four major subtypes such as
luminal A, luminal B, her2-enriched as well as basal-like. On the probe and gene
level, we find that both differentially methylated probes and lncRNAs are subtype
specific, while the lncRNAs are not as specific as probes. On the network level,
the pipeline constructs differential co-methylation lncRNA network for each
subtype. Then, it identifies both subtype specific and common lncRNA modules by
simultaneously analyzing multiple networks. We show that the lncRNAs in subtype
specific and common modules differ greatly in terms of topological structure,
sequence conservation as well as expression. Furthermore, the subtype specific
lncRNA modules serve as biomarkers to improve significantly the accuracy of
breast cancer subtypes prediction. Finally, the common lncRNA modules associate
with survival time of patients, which is critical for cancer therapy.
PMID- 28501297
TI - Are sensitized patients better off with a desensitization transplant or waiting
on dialysis?
AB - Sensitization to human leukocyte antigens (HLAs) remains one of the major
clinical challenges for successful kidney transplantation. Two large
observational studies have recently addressed the question of whether individuals
are better off with a desensitization treatment followed by HLA-incompatible
living donor transplantation or waiting on the deceased donor kidney transplant
list for a compatible transplant. The conflicting results of these 2 studies
largely reflect differences in the study design and study population, leaving
clinicians to make decisions about desensitization based largely on local
expertise and anticipated waiting times for a compatible deceased donor
transplant.
PMID- 28501298
TI - ACE2 as therapy for glomerular disease: the devil is in the detail.
AB - Angiotensin-converting enzyme 2 cleaves angiotensin (Ang) II to Ang(1-7), which
antagonizes the deleterious effects of Ang II. In this issue, 2 groups
administered angiotensin-converting enzyme 2 in murine models of kidney disease.
Angiotensin-converting enzyme 2 did not improve glomerular injury in 2 models of
mild diabetic nephropathy but was partially protective in an Alport syndrome
model. These discrepant findings may be explained by the inability of angiotensin
converting enzyme 2 to reach the urinary space in the absence of severe
proteinuria.
PMID- 28501299
TI - Severe hypertension with renal thrombotic microangiopathy: what happened to the
usual suspect?
AB - Patients with atypical hemolytic uremic syndrome (aHUS) and malignant
hypertension can both present with concomitant hypertension and thrombotic
microangiopathy (TMA), rendering policy decisions complex. Timmermans et al.
report that patients with severe hypertension and renal TMA might have
unrecognized aHUS with underlying complement abnormalities. Based on this, they
assert that all patients presenting with severe hypertension and renal TMA should
be evaluated for aHUS. It remains uncertain whether this holds equally true for
patients with malignant hypertension and renal TMA.
PMID- 28501300
TI - A metabolite-GWAS (mGWAS) approach to unveil chronic kidney disease progression.
AB - In this issue, McMahon et al. report that, by combining phenotypic, metabolomic,
and genetic data, they could better detect chronic kidney disease at the early
stages and provide insight into its pathobiology. The most significant findings
of the study are that several urinary metabolites (e.g., glycine and histidine)
were identified as early risk factors for chronic kidney disease, and metabolites
with genomewide association study analysis identified associations of urinary
metabolites (i.e., lysine and NG-monomethyl-l-arginine) with single-nucleotide
polymorphisms of SLC7A9.
PMID- 28501301
TI - Osteocyte dysfunction and renal osteodystrophy: not just calcium and phosphorus
anymore.
AB - In an important new cross-sectional analysis in this issue, Graciolli and
colleagues present bone data from 148 adult patients across the spectrum of
chronic kidney disease that confirm that disrupted osteocyte function and
abnormal bone histology characterize all stages of chronic kidney disease and
suggest that osteocytic Wnt signaling and osteocyte maturation may play a role in
the pathogenesis of renal osteodystrophy. These concepts may alter how the
skeletal, cardiovascular, and infectious complications of chronic kidney disease
are managed.
PMID- 28501302
TI - Measuring the patient response to dialysis therapy: hemodiafiltration and
clinical trials.
AB - There is a strong biological plausibility for benefit from removal of larger
uremic toxins and increasing positive clinical experience with hemodiafiltration.
However, evidence supporting hemodiafiltration is not definitive with studies
that are often limited by serious methodological shortcomings. Morena et al. show
that hemodiafiltration may prevent intradialytic hypotension, albeit in a study
that also has some shortcomings. Ongoing research for hemodiafiltration is still
needed through high-quality clinical trials that adhere to standards for clinical
trial conduct and reporting.
PMID- 28501303
TI - Potential relevance of shear stress for slit diaphragm and podocyte function.
AB - Filtrate flow through the glomerular barrier produces shear stresses that tend to
disconnect podocytes from the glomerular basement membrane. Forces are highest
within the filtration slits. The slit diaphragm mechanically balances the lateral
components of the shear stresses on opposing foot processes, preventing widening
of the slit.
PMID- 28501304
TI - Speculations on salt and the genesis of arterial hypertension.
AB - Blood pressure salt sensitivity and salt resistance are mechanistically
imperfectly explained. A prescient systems medicine approach by Guyton and
colleagues-more than 50 years ago-suggested how salt intake might influence blood
pressure. They proposed that a high-salt diet engenders sodium accumulation,
volume expansion, cardiac output adjustments, and then autoregulation for flow
maintenance. The autoregulation in all vascular beds increases systemic vascular
resistance, causing the kidneys to excrete more salt and water, thus reducing
systems to normal and minimizing any changes in blood pressure. This schema,
which is remarkably all encompassing, included all regulatory mechanisms Guyton
could identify at the time. Guyton introduced the idea that the kidney is
central, particularly concerning the regulation of renal pressure natriuresis.
Numerous criticisms have been subsequently raised, particularly recently. Kurtz
and colleagues argue that the ability of individuals to respond with an
appropriate vasodilatory response to increased salt intake is pivotal. Data exist
to address that issue. Salt-resistant hypertensive models provide additional
information. We identified a mendelian form of hypertension not related to sodium
reabsorption in the distal nephron. The hypertension develops because of
increased systemic vascular resistance. In addition, we rediscovered a third salt
storage glycose-aminoglycan-related compartment, largely in the skin. This
compartment operates independently of renal function, and when perturbed, is
associated with salt sensitivity. More recently, we found novel molecular
mechanisms demonstrating how large salt quantities are excreted by the kidneys
with minimal water losses. We introduce novel interpretations as to how the
kidneys excrete salt when the intake is high. The findings could have relevance
as to how blood pressure may be regulated at varying salt intakes. Our purposes
are to provide the readership with a banquet of thoughts to digest, to pursue
Guyton's ideas, and to adjust them accordingly.
PMID- 28501305
TI - Modeling citrate excretion.
PMID- 28501306
TI - The Authors Reply.
PMID- 28501307
TI - Modeling amount of acid.
PMID- 28501308
TI - The Authors Reply.
PMID- 28501309
TI - Hematuria from urinary ascariasis.
PMID- 28501311
TI - The Case | An unusual case of recurrent hypokalemic periodic paralysis.
PMID- 28501310
TI - Magnetic resonance lymphangiography in recurrent chylous ascites and chyluria.
PMID- 28501313
TI - Corrigendum to "Believe it or not: Moving non-biological stimuli believed to have
human origin can be represented as human movement" [Cognition 146 (2016) 431
438].
PMID- 28501312
TI - Preschoolers' social experiences and empathy-based responding relate to their
fair resource allocation.
AB - Although the development of fairness has become a topic of wide interest, little
is known about the correlates and factors that relate to the early ontogeny of
fairness-related decision making in preschoolers. The current study assessed 5
year-old children's consideration of existing inequalities in their resource
allocation decisions, that is, their tendency to allocate more resources to poor
others than to rich others. In addition, children's prosocial responding toward
others in pain, the amount of their social interaction experiences, and their
social-cognitive abilities were assessed. The results provide evidence that
children's early social interaction experiences and empathy-based prosocial
responding relate to their fairness-related decision making, supporting a
relational systems approach to early prosocial and moral development.
PMID- 28501314
TI - An Introduction to the Special Issue.
PMID- 28501315
TI - Endovascular stenting for end-stage lung cancer patients with superior vena cava
syndrome post first-line treatments - A single-center experience and literature
review.
AB - BACKGROUND: Superior vena cava (SVC) syndrome is a major complication that occurs
when a growing lung malignancy compresses the SVC extrinsically. Current
treatment options include radiotherapy or chemotherapy to shrink the tumor or
endovascular stenting of the SVC to restore flow. Herein, we report a case series
treated in a single institution to demonstrate the safety, effectiveness, and
outcomes of salvage and primary stenting for malignant SVC obstruction. METHODS:
A total of 12 male patients with malignant superior vena cava obstruction caused
by lung cancer underwent SVC stenting from October 2009 to May 2015. Data were
reviewed retrospectively, including demographic and clinical characteristics,
procedural details, and outcomes. RESULTS: Seven patients had received
radiotherapy prior to SVC stenting, while the other five patients received
stenting as first-line therapy for SVC syndrome. Only one patient experienced
initial symptomatic improvement after radiotherapy, and symptoms of SVC syndrome
recurred one year later. Wallstents(r) (Boston Scientific, Natick MA, USA) were
used in all patients. Preoperatively, the mean narrowest SVC diameter measured by
CT was 2.16 mm (0-5.5 mm). Technical success was achieved in all patients without
complications such as pulmonary embolism, rupture or bleeding. Postoperative mean
narrowest SVC diameter measured by CT during follow-up was 11.17 mm (8-13.5 mm).
Symptoms of SVC syndrome such as arm and face swelling and dyspnea improved
within 1-5 days in all patients. After median follow-up duration of 11.5 months,
only one patient presented recurrent SVC syndrome due to in-stent thrombosis two
months after stenting. CONCLUSION: Salvage SVC stenting remains a safe and
effective treatment for patients with SVC obstruction after failure of
radiotherapy and chemotherapy. Primary stenting may be considered at initial
presentation of SVC syndrome to improve patients' quality of life.
PMID- 28501316
TI - Early initiation of GnRH antagonist administration in a flexible protocol: Is it
better?
PMID- 28501317
TI - [Frequent users and return visits].
PMID- 28501319
TI - Association of pyrethroids exposure with onset of puberty in Chinese girls.
AB - Pyrethroids, a class of ubiquitous insecticides, have been considered as
endocrine-disrupting chemicals (EDCs). Female animal studies suggested that early
life pyrethroids exposure might delay puberty onset. However, it remains unclear
whether this association applies to human populations. A total of 305 girls at
the ages of 9-15 years old were recruited in Hangzhou, China in this study. The
concentration of the common metabolite of pyrethroids, 3-phenoxybenzoic acid (3
PBA), was analyzed in urine samples to reflect the exposure level of pyrethroids.
The associations of 3-PBA with pubertal stages were evaluated using a multinomial
logistic regression model. The geometric mean level of 3-PBA was 1.11 MUg/L (1.42
MUg/g for creatinine-adjusted concentration). There was a significant 45%
reduction in odds of being in breast stage 3 (B3) per one-unit increase in the
log-transformed 3-PBA levels [OR = 0.55 (95%CI: 0.31-0.98), p = 0.042]. A similar
negative association was found between urinary 3-PBA levels with later onset by
pubic hair stage 2 (P2) [OR = 0.56 (95%CI: 0.36-0.90), p = 0.015]. Similar
negative association was also observed between urinary 3-PBA levels and pubertal
onset indicated by menarche [OR = 0.51 (95%CI: 0.28-0.93), p = 0.029]. For the
first time to our knowledge, this work reveals that pyrethroids exposure may
increase the risk of delayed pubertal onset in girls.
PMID- 28501320
TI - Different impacts of bariatric surgical procedures on dyslipidemia: a registry
based analysis.
PMID- 28501318
TI - Mortality, rehospitalization, and post-transplant complications in gender
mismatched heart transplant recipients.
AB - BACKGROUND: Limited research has been published on outcomes in heart transplant
(HT) recipients with gender-mismatched donors. OBJECTIVE: Compare 3-year post
transplant outcomes in 2 groups of gender-mismatched HT recipients and a no
mismatch group. METHODS: Sample: 347 HT recipients: 21.3% (74) received a heart
from the opposite gender: Group 1: same gender donor/recipient (273, 78.7%);
Group 2: female donor/male recipient (40, 11.5%); Group 3: male donor/female
recipient (34, 9.8%). OUTCOMES: mortality, hospitalization, and complications.
RESULTS: Female patients with male heart donors had shorter 3-year survival, were
rehospitalized more days after HT discharge, and had more treated acute rejection
episodes and cardiac allograft vasculopathy. No differences were found in: HT
length of stay, respiratory failure, stroke, cancer, renal dysfunction, steroid
induced diabetes, number of IV-treated infections, or the timing of infection and
rejection. CONCLUSION: Female HT recipients with male donors had worse 3-year
outcomes as compared to male-mismatch and no-mismatch groups.
PMID- 28501321
TI - The effect of close postoperative follow-up on co-morbidity improvement after
bariatric surgery.
AB - BACKGROUND: Patients undergoing gastric bypass (RYGB) surgery require follow-up
for efficacy assessment, early detection of postoperative complications, and also
for management of co-morbid conditions. Recent literature shows support for
improved long-term weight loss with close patient follow-up. However, attrition
rates after RYGB have been reported as high as 50%. OBJECTIVE: The objective of
this study was to assess the relationship between complete follow-up and
improvement or remission of co-morbid conditions at 12 months after surgery.
SETTING: University Hospital, United States. METHODS: Using the Bariatric
Outcomes Longitudinal Database (BOLD) data set, patients with 12-month follow-up
after RYGB were identified. Patients with complete follow-up were compared with
patients who had missed either or both of their 3- and 6-month visits.
Improvement and remission of type 2 diabetes, hypertension, and dyslipidemia were
evaluated at 12-month postoperatively. RESULTS: 46,381 patients (30.6% of all
RYGB patients) were identified that had follow-up with minimum 12-month data.
Complete follow-up was recorded for 75.6% of this group with 12-month data. Of
the 18,629 patients with type 2 diabetes at baseline, 13,498 (72.4%) and 11,287
(60.6%) had improvement and remission, respectively, at 12 months. Improvement in
hypertension and dyslipidemia was noted in 17,808 (62.8%) and 11,602 (55.2%) of
patients, while 13,024 (45.9%) and 9119 (43.4%) had hypertension and dyslipidemia
remission, respectively. After adjusting for baseline characteristics, complete
follow-up in the first year after RYGB was independently associated with a higher
rate of improvement or remission of co-morbid conditions. CONCLUSION: Complete
postoperative follow-up resulted in a higher rate of co-morbidity improvement and
remission compared with incomplete postoperative care. Patients and practices
should strive to achieve complete and long-term follow-up after RYGB surgery.
PMID- 28501322
TI - Extra costs of living with a disability: A review and agenda for research.
AB - BACKGROUND: There has been a growing interest in disability and poverty on the
international research and policy stages. Poverty assessments for persons with
disabilities may be affected by the experience of extra costs associated with a
disability. OBJECTIVE: This article provides a systematized review of the global
literature on the direct costs associated with living with a disability at the
individual or household level. METHODS: We searched three databases for peer
reviewed journal articles that estimated extra costs associated with disability:
Econlit, SocIndex and PubMed. RESULTS: We found 20 such studies conducted in 10
countries. These studies were predominantly from high-income countries. Although
studies were heterogeneous (e.g., in terms of disability measures and cost
methodologies), estimated costs were sizeable and some patterns were consistent
across studies. Costs varied according to the severity of disability, life cycle
and household composition. Highest costs were observed among persons with severe
disabilities, and among persons with disabilities living alone or in small sized
households. CONCLUSIONS: More quantitative evidence is needed using rigorous
methods, for instance evidence based on longitudinal data and as part of policy
evaluations. More internationally comparable data on disability is required for
the quantitative evidence to develop, especially in low- and middle-income
countries where studies are scarce. Qualitative and participatory research is
also needed, especially to investigate unmet needs, and the consequences of extra
costs.
PMID- 28501323
TI - Reliable and practical methods for cryopreservation of embryogenic cultures and
cold storage of somatic embryos of Norway spruce.
AB - Somatic embryogenesis (SE) is considered as the most-effective method for
vegetative propagation of Norway spruce (Picea abies L. Karst). For mass
propagation, a cryopreservation method able to handle large numbers of
embryogenic tissues (ETs) reliably and at low costs is needed. The aim of the
present study was to compare pretreatments, cryoprotectants and slow-cooling
devices for cryopreservation of Norway spruce ETs, with 12 variations of methods
and a total of 136 spruce genotypes. Secondly, possible applications for cold
storage of mature somatic embryos were studied with the aim of developing a
flexible time window for embling production. At best, 100% of the embryogenic
lines were recovered following cryopreservation, but the results varied among the
sets of lines. Also physiological condition of the tissues, pre-treatment and
cryoprotectant applied, as well as the slow-cooling device used were found to
affect the recovery. The best option for cryopreservation of Norway spruce is to
select fresh growth from young ETs as samples, pretreat them on semi-solid medium
with increasing sucrose concentration (0.1 M for 24 h; 0.2 M for another 24 h),
apply a mixture of polyethylene glycol 6000, glucose, and dimethylsulfoxide, 10%
w/v each, as cryoprotectant and use a programmable freezer with a slow cooling
rate (0.17 degrees C/min). On average, 87% of the genotypes can be recovered,
without any effect on their genetic fidelity, as shown by microsatellite markers
and embryo production capacity. Mature somatic embryos of Norway spruce can also
be safely cold-stored at +4 degrees C, without adverse effects on their
germination ability.
PMID- 28501324
TI - Using a new plateau hyperbaric chamber to alleviate high altitude hypoxia: Rabbit
and human studies.
AB - OBJECTIVES: To validate the effects of the new plateau hyperbaric chamber on
alleviating high altitude hypoxia on Mount Kun Lun. METHODS: A prospective,
controlled study of rabbits and adult volunteers was conducted at altitudes of
355, 2880 and 4532m. We obtained arterial blood samples from rabbits and
volunteers before and after hyperbaric treatment. The respiratory rate, heart
rate, and blood pressure (BP) of adult volunteers were monitored during
hyperbaric treatment. RESULTS: The mean PaO2 levels of experimental group rabbits
and volunteers increased significantly after 60min of hyperbaric treatment at
350, 2880 and 4532m. The mean PaCO2 and pH levels of rabbits were not significant
different before and after hyperbaric treatment at each altitude. The mean PaCO2
and pH levels were not significant different at 355m in the human study. However,
at 2880 and 4532m, pH fell with increasing PaCO2 levels in humans before and
after hyperbaric treatment. CONCLUSIONS: The new multiplace plateau hyperbaric
chamber may be used to alleviate plateau hypoxia by increasing patient PaO2.
However, its value in treating AMS must be confirmed in field conditions.
PMID- 28501325
TI - A role for NMDAR-dependent cerebellar plasticity in adaptive control of saccades
in humans.
AB - BACKGROUND: Saccade pulse amplitude adaptation is mediated by the dorsal
cerebellar vermis and fastigial nucleus. Long-term depression at the parallel
fibre-Purkinjie cell synapses has been suggested to provide a cellular mechanism
for the corresponding learning process. The mechanisms and sites of this
plasticity, however, are still debated. OBJECTIVE: To test the role of cerebellar
plasticity phenomena on adaptive saccade control. METHODS: We evaluated the
effect of continuous theta burst stimulation (cTBS) over the posterior vermis on
saccade amplitude adaptation and spontaneous recovery of the initial response. To
further identify the substrate of synaptic plasticity responsible for the
observed adaptation impairment, subjects were pre-treated with memantine, an N
methyl-d-aspartate receptor (NMDAR) antagonist. RESULTS: Amplitude adaptation was
altered by cTBS, suggesting that cTBS interferes with cerebellar plasticity
involved in saccade adaptation. Amplitude adaptation and spontaneous recovery
were not affected by cTBS when recordings were preceded by memantine
administration. CONCLUSION: The effects of cTBS are NMDAR-dependent and are
likely to involve long-term potentiation or long-term depression at specific
synaptic connections of the granular and molecular layer, which could effectively
take part in cerebellar motor learning.
PMID- 28501326
TI - Management of Platelet Disorders and Platelet Transfusions in ICU Patients.
AB - Thrombocytopenia or receipt of antiplatelet drugs, with or without bleeding, is a
common indication for platelet transfusions in the ICU. However, there is almost
no evidence base for these practices other than expert opinion. Also common is
use of platelet transfusions prior to invasive procedures or surgery in patients
with thrombocytopenia. Likewise, there is no high-quality evidence that such
practices are efficacious or safe. Recently, it has become clear that, whether
causal or not, patients receiving prophylactic platelet transfusions experience
high rates of nosocomial infection, thrombosis, organ failure, and mortality,
which increase the urgency and need for randomized trials to assess these
practices. Investigational methods of improving the safety and efficacy of
platelet transfusions include use of alternate strategies such as
antifibrinolytics; use of ABO-identical, leukoreduced, and washed platelet
transfusions; and improved storage solutions.
PMID- 28501327
TI - Echo Particle Image Velocimetry for Estimation of Carotid Artery Wall Shear
Stress: Repeatability, Reproducibility and Comparison with Phase-Contrast
Magnetic Resonance Imaging.
AB - Measurement of hemodynamic wall shear stress (WSS) is important in investigating
the role of WSS in the initiation and progression of atherosclerosis. Echo
particle image velocimetry (echo PIV) is a novel ultrasound-based technique for
measuring WSS in vivo that has previously been validated in vitro using the
standard optical PIV technique. We evaluated the repeatability and
reproducibility of echo PIV for measuring WSS in the human common carotid artery.
We measured WSS in 28 healthy participants (18 males and 10 females, mean age: 56
+/- 12 y). Echo PIV was highly repeatable, with an intra-observer variability of
1.0 +/- 0.1 dyn/cm2 for peak systolic (maximum), 0.9 dyn/cm2 for mean and 0.5
dyn/cm2 for end-diastolic (minimum) WSS measurements. Likewise, echo PIV was
reproducible, with a low inter-observer variability (max: 2.0 +/- 0.2 dyn/cm2,
mean: 1.3 +/- 0.1 dyn/cm2, end-diastolic: 0.7 dyn/cm2) and more variable inter
scan (test-retest) variability (max: 7.1 +/- 2.3 dyn/cm2, mean: 2.9 +/- 0.4
dyn/cm2, min: 1.5 +/- 0.1 dyn/cm2). We compared echo PIV with the reference
method, phase-contrast magnetic resonance imaging (PC-MRI); echo PIV-based WSS
measurements agreed qualitatively with PC-MRI measurements (r = 0.89, p < 0.05).
Significant differences were observed in some WSS measurements (echo PIV vs. PC
MRI): WSS at peak systole: 21 +/- 7.0 dyn/cm2 vs. 15 +/- 5.0 dyn/cm2; time
averaged WSS: 8.9 +/- 3.0 dyn/cm2 vs. 7.1 +/- 3.0 dyn/cm2 (p < 0.05); WSS at end
diastole: 3.8 +/- 2.8 dyn/cm2 vs. 3.9 +/- 2 dyn/cm2 (p > 0.05). For the first
time, we report that echo PIV can measure WSS with good repeatability and
reproducibility in adult humans with a broad age range. Echo PIV is feasible in
humans and offers an easy-to-use, ultrasound-based, quantitative technique for
measuring WSS in vivo in humans with good repeatability and reproducibility.
PMID- 28501328
TI - Evaluation of venous thrombosis and tissue factor in epithelial ovarian cancer.
AB - OBJECTIVE: Ovarian clear cell carcinoma (OCCC) and high grade serous ovarian
cancer (HGSOC) are associated with the highest risk of VTE among patients with
epithelial ovarian cancer (EOC). Tissue factor (TF) is a transmembrane
glycoprotein which can trigger thrombosis. We sought to evaluate if there is an
association between VTE and tumor expression of tissue factor (TF), plasma TF,
and microvesicle TF (MV TF) activity in this high-risk population. METHODS: We
performed a case-control study of OCCC and HGSOC patients with and without VTE.
105 patients who underwent surgery at a tertiary care center between January 1995
and October 2013 were included. Plasma TF was measured with an enzyme-linked
immunosorbent assay. A TF-dependent Factor Xa generation assay was used to
measure MV TF activity. Immunohistochemical (IHC) analysis was performed to
evaluate tumor expression of TF. RESULTS: 35 women with OCCC or HGSOC diagnosed
with VTE within 9months of surgery were included in the case group. Those with
VTE had a worse OS, p<0.0001, with a greater than three-fold increase in risk of
death, HR 3.33 (CI 1.75-6.35). There was no significant difference in median
plasma TF level or MV TF activity level between patients with and without VTE.
OCCC patients had greater expression of TF in their tumors than patients with
HGSOC, p<0.0001. CONCLUSIONS: TFMV activity and plasma TF level were not
predictive of VTE in this patient population. Given the extensive expression of
TF in OCCC tumors, it is unlikely IHC expression will be useful in risk
stratification for VTE in this population.
PMID- 28501329
TI - Eukaryotic DNA replication: Orchestrated action of multi-subunit protein
complexes.
AB - Genome duplication is an essential process to preserve genetic information
between generations. The eukaryotic cell cycle is composed of functionally
distinct phases: G1, S, G2, and M. One of the key replicative proteins that
participate at every stage of DNA replication is the Mcm2-7 complex, a
replicative helicase. In the G1 phase, inactive Mcm2-7 complexes are loaded on
the replication origins by replication-initiator proteins, ORC and Cdc6. Two
kinases, S-CDK and DDK, convert the inactive origin-loaded Mcm2-7 complex to an
active helicase, the CMG complex in the S phase. The activated CMG complex begins
DNA unwinding and recruits enzymes essential for DNA synthesis to assemble a
replisome at the replication fork. After completion of DNA synthesis, the
inactive CMG complex on the replicated DNA is removed from chromatin to terminate
DNA replication. In this review, we will discuss the structure, function, and
regulation of the molecular machines involved in each step of DNA replication.
PMID- 28501331
TI - The expression of keratin 6 is regulated by the activation of the ERK1/2 pathway
in arsenite transformed human urothelial cells.
AB - Urothelial cancers have an environmental etiological component, and previous
studies from our laboratory have shown that arsenite (As+3) can cause the
malignant transformation of the immortalized urothelial cells (UROtsa), leading
to the expression of keratin 6 (KRT6). The expression of KRT6 in the parent
UROtsa cells can be induced by the addition of epidermal growth factor (EGF).
Tumors formed by these transformed cells have focal areas of squamous
differentiation that express KRT6. The goal of this study was to investigate the
mechanism involved in the upregulation of KRT6 in urothelial cancers and to
validate that the As+3-transformed UROtsa cells are a model of urothelial cancer.
The results obtained showed that the parent and the As+3-transformed UROtsa cells
express EGFR which is phosphorylated with the addition of epidermal growth factor
(EGF) resulting in an increased expression of KRT6. Inhibition of the
extracellular-signal regulated kinases (ERK1/2) pathway by the addition of the
mitogen-activated protein kinase kinase 1 (MEK1) and MEK2 kinase inhibitor U0126
resulted in a decrease in the phosphorylation of ERK1/2 and a reduced expression
of KRT6. Immuno-histochemical analysis of the tumors generated by the As+3
transformed isolates expressed EGFR and tumors formed by two of the transformed
isolates expressed the phosphorylated form of EGFR. These results show that the
expression of KRT6 is regulated at least in part by the ERK1/2 pathway and that
the As+3-transformed human urothelial cells have the potential to serve as a
valid model to study urothelial carcinomas.
PMID- 28501330
TI - Virus entry and replication in the brain precedes blood-brain barrier disruption
during intranasal alphavirus infection.
AB - Viral infections of the central nervous system (CNS) are often associated with
blood-brain barrier (BBB) disruption, yet the impact of virus replication and
immune cell recruitment on BBB integrity are incompletely understood. Using two
photon microscopy, we demonstrate that Venezuelan equine encephalitis virus
(VEEV) strain TC83-GFP, a GFP expressing, attenuated strain with a G3A mutation
within the 5' UTR that is associated with increased sensitivity to type I
interferons (IFNs), does not directly impact BBB permeability. Following
intranasal infection of both wild-type and IFN-induced protein with
tetratricopeptide repeats 1 (IFIT1)-deficient mice, which fail to block TC83
specific RNA translation, virus spreads to the olfactory bulb and cortex via
migration along axonal tracts of neurons originating from the olfactory
neuroepithelium. Global dissemination of virus in the CNS by 2days post-infection
(dpi) was associated with increased BBB permeability in the olfactory bulb, but
not in the cortex or hindbrain, where permeability only increased after the
recruitment of CX3CR1+ and CCR2+ mononuclear cells on 6 dpi, which corresponded
with tight junction loss and claudin 5 redistribution. Importantly, despite
higher levels of viral replication, similar results were obtained in IFIT1
deficient mice. These findings indicate that TC83 gains CNS access via
anterograde axonal migration without directly altering BBB function and that
mononuclear and endothelial cell interactions may underlie BBB disruption during
alphavirus encephalitis.
PMID- 28501333
TI - Comparative effectiveness of faecal microbiota transplant by route of
administration.
AB - The optimal route of delivery for faecal microbiota transplant (FMT) is unknown.
This observational single-centre study analysed the two-week cure rates for all
patients who received FMT from 2013 to 2016 according to route of delivery.
Overall, nasogastric delivery of FMT was less effective than lower endoscopic
delivery. When patients were stratified by illness severity, nasogastric delivery
achieved similar cure rates in healthier individuals, whereas lower endoscopic
delivery was preferred for relatively ill individuals. Nasogastric delivery may
be less effective than lower endoscopic delivery; however, when taking the cost,
preparation and potential risk into account, this difference may not be
clinically significant for patients with mild disease.
PMID- 28501332
TI - Inhibition of nicotinamide phosphoribosyltransferase and depletion of
nicotinamide adenine dinucleotide contribute to arsenic trioxide suppression of
oral squamous cell carcinoma.
AB - Emerging evidence suggests that increased nicotinamide phosphoribosyltransferase
(NAMPT) expression is associated with the development and prognosis of many
cancers, but it remains unknown regarding its role in oral squamous cell
carcinoma (OSCC). In the present study, the results from tissue microarray showed
that NAMPT was overexpressed in OSCC patients and its expression level was
directly correlated with differential grades of cancer. Interestingly, treatment
of OSCC cells with chemotherapy agent arsenic trioxide (ATO) decreased the levels
of NAMPT protein and increased cellular death in an ATO dose- and time-dependent
manner. Most importantly, combination of low concentration ATO with FK866 (a
NAMPT inhibitor) exerted enhanced inhibitive effect on NAMPT protein and mRNA
expressions, leading to synergistic cytotoxicity on cancer cells through
increasing cell apoptosis and depleting intracellular nicotinamide adenine
dinucleotide levels. These findings demonstrate the crucial role of NAMPT in the
prognosis of OSCC and reveal inhibition of NAMPT as a novel mechanism of ATO in
suppressing cancer cell growth. Our results suggest that ATO can significantly
enhance therapeutic efficacy of NAMPT inhibitor, and combined treatment may be a
novel and effective therapeutic strategy for OSCC patients.
PMID- 28501335
TI - Obtaining of granular fertilizers based on ashes from combustion of waste
residues and ground bones using phosphorous solubilization by bacteria Bacillus
megaterium.
AB - The article presents research results on obtaining phosphorus granulated
fertilizers on the basis of microbiologically activated sewage sludge ashes,
ground bones and dried blood from meat industry. Granulation tests were carried
out using a laboratory pan granulator as well as on an experimental pilot plant.
The aim of the studies was to select the proper composition of the mixture of raw
materials and binding agents to obtain granulated fertilizers from waste
materials such as MSSA and MBM and bacteria lyophilisate. Obtained fertilizer
samples were subjected to physical tests (granulation tests etc.) and quality
assessment. The tests confirmed that it was possible to produce granulated
phosphate fertilizers using the Bacillus megaterium for solubilization of
phosphorus in a simple process.
PMID- 28501334
TI - Exchangeable Sodium Percentage decrease in saline sodic soil after Basic Oxygen
Furnace Slag application in a lysimeter trial.
AB - The Basic Oxygen Furnace Slag results from the conversion of hot metal into
steel. Some properties of this slag, such as the high pH or calcium and magnesium
content, makes it suitable for agricultural use as a soil amendment. Slag
application to agricultural soils is allowed in some European countries, but to
date there is no common regulation in the European Union. In Italy soils in
coastal areas are often affected by excess sodium, which has several detrimental
effects on the soil structure and crop production. In this study, carried out
within an European project, the ability of the Basic Oxygen Furnace Slag to
decrease the soil Exchangeable Sodium Percentage of a sodic soil was evaluated. A
three-year lysimeter trial with wheat and tomato crops was carried out to assess
the effects of two slag doses (D1, 3.5 g kg-1year-1 and D, 2, 7 g kg-1year-1) on
exchangeable cations in comparison with unamended soil. In addition, the
accumulation in the topsoil of vanadium and chromium, the two main trace metals
present in the Basic Oxygen Furnace Slag, was assessed. After two years, the soil
Exchangeable Sodium Percentage was reduced by 40% in D1 and 45% in D2 compared to
the control. A concomitant increase in exchangeable bivalent cations (Ca++ and
Mg++) was observed. We concluded that bivalent cations supplied with the slag
competed with sodium for the sorption sites in the soil. The slag treatments also
had a positive effect on tomato yields, which were higher than the control.
Conversely the wheat yield was lower in the slag-amended soil, possibly because
of the toxicity of vanadium added with the slag. This study showed that Basic
Oxygen Furnace Slag decreased the Exchangeable Sodium Percentage, but precautions
are needed to avoid the build up of toxic concentrations of trace metals in the
soil, especially vanadium.
PMID- 28501336
TI - Bioethanol production from recovered napier grass with heavy metals.
AB - Using plants to absorb and accumulate heavy metals from polluted soil, followed
by the recycling of explants containing heavy metals, can help achieve the goal
of reverting contaminated soil to low heavy-metal content soil. However, the re
use of recovered explants can also be problematic. Meanwhile, bioethanol has
become a popular energy source. In this study, napier grass was used for the
remediation of soil contaminated with heavy metals (artificially contaminated
soil). The influence of bioethanol production from napier grass after
phytoremediation was also investigated. The concentration of Zn, Cd, and Cr in
the contaminated soil was 1000, 100, and 250 mg/kg, respectively. After napier
grass phytoremediation, the concentration (dry biomass) of Zn, Cd, and Cr in the
explants was 2701.97 +/- 173.49, 6.1 +/- 2.3, and 74.24 +/- 1.42 mg/kg,
respectively. Biomass production in the unpolluted soil was 861.13 +/- 4.23 g.
The biomass production ratio in high Zn-polluted soil was only 3.89%, while it
was 4.68% for Cd and 21.4% for Cr. The biomass obtained after napier grass
phytoremediation was pretreated using the steam explosion conditions of 180
degrees C, for 10 min, with 1.5% H2SO2, followed by enzymatic hydrolysis. The
efficiency of enzymatic hydrolysis for Zn-polluted biomass was 90% of the
unpolluted biomass, while it was 77% for Cd, and approximately the same for Cr.
The fermentation efficiency of the heavy-metal-containing biomass was higher than
the control biomass. The fermentation ethanol concentration obtained was 8.69
12.68, 13.03-15.50, and 18.48-19.31 g/L in Zn, Cd, and Cr environments,
respectively. Results show that the heavy metals had a positive effect on
bacteria fermentation. However, the fermentation efficiency was lower for biomass
with severe heavy metal pollution. Thus, the utilization of napier grass
phytoremediation for bioethanol production has a positive effect on the
sustainability of environmental resources.
PMID- 28501337
TI - Late In-Hospital Management of Patients Hospitalized with Acute Heart Failure.
AB - Acute Heart Failure (AHF) hospitalization presents a significant financial burden
and portends a poor prognosis following discharge. As such, there has been
significant emphasis on the late inpatient management of patients hospitalized
with AHF to ensure successful transition to the outpatient setting and to reduce
overall readmission and mortality rates. Thorough discharge planning and a
multidisciplinary team approach are essential and as outlined in this review
should focus on four key elements: the assessment of patients' readiness for
discharge, optimization of goal directed medical therapy and appropriate device
therapy, patient education and transition to the outpatient care.
PMID- 28501338
TI - Risk factors for metabolic syndrome after liver transplantation: A systematic
review and meta-analysis.
AB - INTRODUCTION: Metabolic syndrome is associated with increased risk of
cardiovascular events, which contributes to the elevated mortality rate among
liver transplant recipients. The objective of this systematic review and meta
analysis was to assess the prevalence and risk factors for metabolic syndrome
after liver transplantation. METHODS: The databases Medline and Scopus were
searched for observational studies evaluating prevalence and risk factors for
metabolic syndrome after liver transplantation. Meta-analyses were performed
based on odds ratios (ORs) from multivariable analyses. The Newcastle-Ottawa
Scale was used for assessment of bias. RESULTS: The literature search generated
1815 records of which 16 articles were included comprising 3539 patients. The
post-transplant prevalence of metabolic syndrome was 39%. Eight studies were
eligible for meta-analyses, which showed that pre-transplant diabetes (OR=3.54,
95% confidence interval (CI): 2.51-4.98) and pre-transplant obesity (OR=2.44, 95%
CI: 1.48-4.03) were risk factors for metabolic syndrome. Six out of seven studies
reported that recipients with metabolic syndrome had a higher incidence of
cardiovascular events. Four studies showed that survival was not affected by
metabolic syndrome. CONCLUSIONS: The prevalences of metabolic syndrome and new
onset metabolic syndrome were high after liver transplantation. Metabolic
syndrome was associated with cardiovascular events, but not poorer survival.
Patients with pre-transplant diabetes and -obesity are at high risk of metabolic
syndrome and should be under careful surveillance in order to prevent, earlier
diagnose, and treat metabolic syndrome and thereby limit the risk of
cardiovascular events.
PMID- 28501339
TI - X-ray free electron laser single-particle analysis for biological systems.
AB - The X-ray free electron laser (XFEL) is a new light source that can produce
coherent, ultra-brilliant, femtosecond X-ray pulses. This X-ray beam provides new
possibilities for studies in structural biology. In this review, we survey the
applications of XFEL to biological systems, with an emphasis on studies of
noncrystalline samples. Although atomic-level modeling is not yet achievable,
this method enables high-throughput, damage-free imaging of biological samples
under near-physiological conditions and is being rapidly developed. Here, we
provide overviews of XFEL technology, experimental techniques, and computational
data analyses, and discuss examples of such studies.
PMID- 28501340
TI - Gliding Resistance After Epitendinous-First Repair of Flexor Digitorum Profundus
in Zone II.
AB - PURPOSE: The importance of flexor tendon repair with both core and epitendinous
suture placement has been well established. The objective of this study was to
determine whether suture placement order affects gliding resistance and bunching
in flexor digitorum profundus tendons in a human ex vivo model. METHODS: The
flexor digitorum profundus tendons of the index, middle, ring, and little fingers
of paired cadaver forearms were tested intact for excursion and mean gliding
resistance in flexion and extension across the A2 pulley. Tendons were
subsequently transected and repaired with either an epitendinous-first (n = 12)
or a control (n = 12) repair. Gliding resistance of pair-matched tendons were
analyzed at cycle 1 and during the steady state of tendon motion. The tendon
repair breaking strength was also measured. RESULTS: The mean steady state
gliding resistance was less for the epitendinous-first repair than for the
control repair in flexion (0.61 N vs 0.72 N) and significantly less in extension
(0.68 N vs 0.85 N). Similar results were seen for cycle 1. None of the repairs
demonstrated gap formation; however, control repairs exhibited increased
bunching. Load to failure was similar for both groups. CONCLUSIONS: The order of
suture placement for flexor tendon repair is important. Epitendinous-first repair
significantly decreased mean gliding resistance, allowed for easier placement of
core sutures, and resulted in decreased bunching. CLINICAL RELEVANCE:
Epitendinous-first flexor tendon repairs may contribute to improved clinical
outcomes compared with control repairs by decreasing gliding resistance and
bunching.
PMID- 28501341
TI - Chronic Boutonniere Deformity: Cross-Lateral Band Technique Using Palmaris Longus
Autograft.
AB - PURPOSE: The purpose of this study was to evaluate the outcomes of treatment of
chronic boutonniere deformity with a reconstruction technique using palmaris
longus autograft. MATERIALS AND METHODS: Seven patients with chronic,
posttraumatic, flexible boutonniere deformities referred to our clinic between
January 2010 and September 2014 were included in the study. In all 7 patients,
the lateral bands were deficient or damaged beyond repair. A novel reconstruction
technique for chronic boutonniere deformity utilizing palmaris longus autograft
was used. The 2 lateral bands were reconstructed by attaching the palmaris longus
tendon grafts from the lateral part of the central slip proximally to the volar
aspect of the distal phalanx distally using pull-out sutures. The grafts were
positioned so that they crossed over one another at the level of the middle
phalanx. The patients were followed for a mean of 14 months (range, 12-16
months). The principal outcome measure was the range of motion of the proximal
(PIP) and distal (DIP) interphalangeal joints. RESULTS: Before surgery, the
average PIP joint active flexion was 69 degrees (range, 60 degrees -85 degrees
). After surgery, the average PIP joint active flexion increased to 92 degrees
(range, 90 degrees -100 degrees ). Before surgery, the average PIP joint
extension deficit was 54 degrees (range, 40 degrees -60 degrees ); after
surgery, the average deficit was reduced to 7 degrees (range, 5 degrees -15
degrees ). Before surgery, the average DIP posture was 9 degrees of
hyperextension (range, 5 degrees -12 degrees ); after surgery, DIP hyperextension
was reduced to 2 degrees (range, 0 degrees -5 degrees ). Before surgery, the
average DIP active flexion was 40 degrees (range, 35 degrees -55 degrees );
after surgery, this increased to 55 degrees (range, 43 degrees -72 degrees ). No
patients developed a DIP flexion contracture. CONCLUSIONS: In the chronic
boutonniere deformity, when the lateral bands are deficient or damaged, our cross
lateral band reconstruction technique using palmaris longus autograft is a
treatment option with satisfactory results. TYPE OF STUDY/LEVEL OF EVIDENCE:
Therapeutic V.
PMID- 28501342
TI - Speed, age, sex, and body mass index provide a rigorous basis for comparing the
kinematic and kinetic profiles of the lower extremity during walking.
AB - The increased use of gait analysis has raised the need for a better understanding
of how walking speed and demographic variations influence asymptomatic gait.
Previous analyses mainly reported relationships between subsets of gait features
and demographic measures, rendering it difficult to assess whether gait features
are affected by walking speed or other demographic measures. The purpose of this
study was to conduct a comprehensive analysis of the kinematic and kinetic
profiles during ambulation that tests for the effect of walking speed in parallel
to the effects of age, sex, and body mass index. This was accomplished by
recruiting a population of 121 asymptomatic subjects and analyzing characteristic
3-dimensional kinematic and kinetic features at the ankle, knee, hip, and pelvis
during walking trials at slow, normal, and fast speeds. Mixed effects linear
regression models were used to identify how each of 78 discrete gait features is
affected by variations in walking speed, age, sex, and body mass index. As
expected, nearly every feature was associated with variations in walking speed.
Several features were also affected by variations in demographic measures,
including age affecting sagittal-plane knee kinematics, body mass index affecting
sagittal-plane pelvis and hip kinematics, body mass index affecting frontal-plane
knee kinematics and kinetics, and sex affecting frontal-plane kinematics at the
pelvis, hip, and knee. These results could aid in the design of future studies,
as well as clarify how walking speed, age, sex, and body mass index may act as
potential confounders in studies with small populations or in populations with
insufficient demographic variations for thorough statistical analyses.
PMID- 28501343
TI - Changes of renal sinus fat and renal parenchymal fat during an 18-month
randomized weight loss trial.
AB - BACKGROUND & AIMS: Data regarding the role of kidney adiposity, its clinical
implications, and its dynamics during weight-loss are sparse. We investigated the
effect of long-term weight-loss induced intervention diets on dynamics of renal
sinus-fat, an ectopic fat depot, and %renal-parenchymal-fat, lipid accumulation
within the renal parenchyma. METHODS: We randomized 278 participants with
abdominal obesity/dyslipidemia to low-fat or Mediterranean/low-carbohydrate
diets, with or without exercise. We quantified renal-sinus-fat and %renal
parenchymal-fat by whole body magnetic-resonance-imaging. RESULTS: Participants
(age = 48 years; 89% men; body-mass-index = 31 kg/m2) had 86% retention to the
trial after 18 months. Both increased renal-sinus-fat and %renal-parenchymal-fat
were directly associated with hypertension, and with higher abdominal deep
subcutaneous-adipose-tissue and visceral-adipose-tissue (p of trend < 0.05 for
all) after adjustment for body weight. Higher renal-sinus-fat was associated with
lower estimated-glomerular-filtration-rate and with higher microalbuminuria and
%HbA1C beyond body weight. After 18 months of intervention, overall renal-sinus
fat (-9%; p < 0.05 vs. baseline) but not %renal-parenchymal-fat (-1.7%; p = 0.13
vs. baseline) significantly decreased, and similarly across the intervention
groups. Renal-sinus-fat and %renal-parenchymal-fat changes were correlated with
weight-loss per-se (p < 0.05). In a model adjusted for age, sex, and visceral
adipose-tissue changes, 18 months reduction in renal-sinus-fat associated with
decreased pancreatic, hepatic and cardiac fats (p < 0.05 for all) and with
decreased cholesterol/high-density lipoprotein-cholesterol (HDL-c) (beta = 0.13;
p = 0.05), triglycerides/HDL-c (beta = 0.13; p = 0.05), insulin (beta = 0.12; p =
0.05) and gamma glutamyl transpeptidase (beta = 0.24; p = 0.001), but not with
improved renal function parameters or blood pressure. Decreased intake of sodium
was associated with a reduction in %renal-parenchymal-fat, after adjustment for
18 months weight-loss (beta = 0.15; p = 0.026) and hypertension (beta = 0.14; p =
0.04). CONCLUSIONS: Renal-sinus-fat and renal-parenchymal-fat are fairly related
to weight-loss. Decreased renal-sinus-fat is associated with improved hepatic
parameters, independent of changes in weight or hepatic fat, rather than with
improved renal function or blood pressure parameters. CLINICALTRIALS.
GOVIDENTIFIER: NCT01530724.
PMID- 28501344
TI - Kaposi Sarcoma and Lung Transplant: Two Case Reports.
PMID- 28501345
TI - Incidental Finding of Right Pulmonary Artery Agenesis in an Adult.
PMID- 28501346
TI - IL-13 and idiopathic pulmonary fibrosis: Possible links and new therapeutic
strategies.
AB - The recent advances in the knowledge of immunological aspects of many pulmonary
diseases, allowed to identify cells, biological functions, cytokines, and
receptors that are preferentially involved in each disease. This is the case of
asthma, where IL-13 (together with IL-4) is recognized as a central mediator. The
role of IL-13 is strictly related, via complex signaling pathways, to eosinophil
recruitment and activation, to mucus secretion, periostin generation and to
fibrogenic processes (which are part of the remodeling process). These peculiar
roles of IL-13 have suggested the hypothesis of its role in Idiopathic Pulmonary
Fibrosis, and consequently of its antagonists in the treatment of such disease.
We review herein the immunological roles of IL-13 in asthma and IPF, and the
currently ongoing attempts to treat IPF by IL-13 antagonism strategies.
PMID- 28501347
TI - Defective protein prenylation is a diagnostic biomarker of mevalonate kinase
deficiency.
PMID- 28501349
TI - Potential health impact and cost-effectiveness of drug therapy for
prehypertension.
AB - BACKGROUND: Studies have reported that pharmacologic interventions with
candesartan or ramipril could reduce the risk of hypertension among
prehypertensive subjects free of clinical cardiovascular disease (CVD), however,
the cost-effectiveness and long-term cardiovascular risk of drug treatment among
these population is unclear. METHOD: A Markov state-transition model was
developed to simulate a hypothetical cohort of Chinese adults with high-range
prehypertension (130-139/85-89mmHg) but without CVD. Data on the incidence of CVD
and hypertension was obtained from corresponding risk equations. Utility and
disease-related costs were obtained from published literatures. Robustness and
uncertainty was evaluated using deterministic and probabilistic sensitivity
analyses. RESULTS: Compared with placebo, drug treatment resulted in delaying the
development of hypertension by nearly 12years and reducing the absolute incidence
of hypertension by 32.01% over lifetime. The cumulative incidence of coronary
heart disease, stroke and heart failure were reduced and survival was improved
from 28.46 to 28.80years. The average incremental cost effectiveness ratio for
drug treatment was $12,994 per quality-adjusted life-year and the value was
mostly sensitive to the effect size of treatment and age starting treatment. At a
willingness-to-pay threshold of >3*China gross domestic product per capita in
2014, there was a 30.48% chance that drug treatment would remain cost-effective
and a low chance of being cost-effective if relative risk of treatment on
hypertension was larger than 0.64. CONCLUSION: Drug treatment for prehypertension
may help stem the current epidemic of hypertension among Chinese adults free of
CVD, which may in turn reduce CVD complications and potentially be cost
effective.
PMID- 28501348
TI - Single-Cell RNA Sequencing: Unraveling the Brain One Cell at a Time.
AB - Single-cell RNA sequencing (scRNA-seq) is an exciting new technology allowing the
analysis of transcriptomes from individual cells, and is ideally suited to
address the inherent complexity and dynamics of the central nervous system. scRNA
seq has already been applied to the study of molecular taxonomy of the brain.
These works have paved the way to expanding our understanding of the nervous
system and provide insights into cellular susceptibilities and molecular
mechanisms in neurological and neurodegenerative diseases. We discuss recent
progress and challenges in applying this technology to advance our understanding
of the brain. We advocate the application of scRNA-seq in the discovery of
targets and biomarkers as a new approach in developing novel therapeutics for the
treatment of neurodegenerative diseases.
PMID- 28501350
TI - First in man prolonged pressure-controlled intermittent coronary sinus occlusion
to treat refractory left ventricular dysfunction and ischemia with patent
epicardial coronary arteries.
AB - AIMS: Pressure-controlled Intermittent Coronary Sinus Occlusion (PICSO)
intermittently increases the pressure in the cardiac venous outflow tract using a
balloon-tipped catheter introduced percutaneously into the coronary sinus. It
aims to improve microvascular perfusion in STEMI patients during PCI, thus
improving infarct healing. Its successful administration was associated with an
improvement in myocardial recovery four months after primary-PCI as compared to
control. However, it has never been used in other settings or for a prolonged
period. The aim of this study was to report on the feasibility and efficacy of
prolonged PICSO to treat refractory LV dysfunction and ischemia. METHODS AND
RESULTS: Two patients with refractory LV dysfunction and ongoing ischemia with
patent epicardial coronary artery and suspected underlying microvascular
dysfunction were treated with prolonged off-label PICSO utilization. A medium of
23,990mmHg PICSO quantity (a marker of PICSO therapy performance) was achieved:
it was almost fifty times the PICSO quantity previously reported in in short-term
PICSO utilization. After PICSO placement, both patients showed significant
improvement of myocardial ischemia and recovery of LV systolic function.
CONCLUSION: Prolonged PICSO utilization was feasible and effective in two
patients. These cases highlight a novel application of PICSO technology:
redistribution of venous blood and improvement in microvascular perfusion that
might be a new target in cases of refractory LV dysfunction and ongoing ischemia
in the setting of patent epicardial coronary arteries.
PMID- 28501351
TI - Author's reply: Assessment of current use of guideline-based medical therapy in
elderly patients with heart failure.
PMID- 28501352
TI - Effects of glucagon-like peptide-1 receptor agonists on mortality and
cardiovascular events: A comprehensive meta-analysis of randomized controlled
trials.
AB - INTRODUCTION: The publication of the results of LEADER and SUSTAIN-6 trials
suggested a possible beneficial effect of the class of GLP-1 receptor agonists on
cardiovascular morbidity and mortality. The aim of the present meta-analysis is
to collect and synthetize all available evidence on the effect of GLP-1 receptor
agonists on cardiovascular events and mortality. METHODS: A Medline search for
GLP-1 receptor agonists (exenatide, liraglutide, lixisenatide, albiglutide,
dulaglutide, or semaglutide) was performed, collecting all randomized clinical
trials with a duration >11weeks, enrolling patients with type 2 diabetes, and
comparing a GLP-1 receptor agonist with placebo or any other non-GLP-1 receptor
agonist drug. The principal outcome of this analysis was the effect of GLP-1
receptor agonists on all-cause and cardiovascular mortality, overall (fatal plus
nonfatal) myocardial infarction, stroke, and heart failure. RESULTS: Out of 113
trials fulfilling inclusion criteria (mean duration 41.7+/-38.2weeks), 32, 25,
48, 43 and 32 reported at least one event for all-cause and cardiovascular
mortality, overall (fatal plus nonfatal) myocardial infarction, stroke, and heart
failure, respectively. In GLP-1 receptor agonist-treated patients, all-cause
mortality, cardiovascular mortality, and myocardial infarction were significantly
lower than in comparators (MH-OR [95% CI] 0.88 [0.79-0.97], p=0.015, 0.84 [0.74
0.96], p=0.009, and 0.90 [0.80-1.00], p=0.050, respectively), whereas no
beneficial effect was observed for stroke and heart failure (MH-OR [95% CI] 0.90
[0.81-1.00]. p=0.059. 0.89 [0.76-1.04]. p=0.15. and 0.92 [0.81-1.06]. p=0.25.
respectively). CONCLUSIONS: Overall, the agents of this class appear to reduce
all-cause mortality, cardiovascular mortality, and the incidence of myocardial
infarction at mid-term follow up.
PMID- 28501353
TI - Beta-tricalcium phosphate for orthopedic reconstructions as an alternative to
autogenous bone graft.
AB - : Autogenous bone graft (autograft) remains the gold standard in the treatment of
many orthopedic problems. However, graft harvest can lead to perioperative
morbidity and increased cost. We tested the hypothesis that an osteoconductive
matrix, beta-tricalcium phosphate (beta-TCP), would be a safe and effective
alternative to autograft alone. Beta-tricalcium phosphate (beta-TCP) is
considered as one of the most promising biomaterials for bone reconstruction.
This study analyzes the outcomes of patients who received beta-TCP as bone
substitutes in orthopedic surgery. METHODS: A total of 50 patients were enrolled
in a controlled, non-inferiority clinical trial to compare the safety and
efficacy of beta-TCP (25 patients) with those of autograft (25 patients) in
indications requiring usually autograft. These 50 patients were categorized
according to the etiology and morphology of the 54 bone defects resulting from
elective surgical procedures, such as 34 open-wedge high tibial osteotomies, and
20 osteonecrosis treatments with core decompression. Radiographic (healing
process with or without integration of beta-TCP), clinical (no other surgical
procedure), functional outcomes and safety (with or without complications) were
assessed through fifty-two weeks postoperatively. RESULTS: With regard to the
primary endpoint (radiographic evolution), the fusion rate of the 34 open-wedge
osteotomies was 100% (17 among 17) for patients in the group with beta-TCP
compared with 94% (16 among 17) for patients in the autograft group. For the 20
cavitary defects (osteonecrosis), the radiographic union rates, as determined by
the presence of osseous bridging, were 100% for patients in the group with beta
TCP and 100% for those in the autograft group. Clinically at one year, all
quality-of-life and functional outcome data supported non-inferiority of beta-TCP
compared with autograft, and patients in the beta-TCP group were found to have
less pain and an improved safety profile. CONCLUSIONS: Treatment with beta-TCP
resulted in comparable fusion rates, less pain and fewer side effects as compared
with treatment with autograft. This study established clinical parameters where
the beta-TCP alone can successfully support the osteogenic process.
PMID- 28501354
TI - Calcium orthophosphates (CaPO4): Occurrence and properties.
AB - The present overview is intended to point the readers' attention to the important
subject of calcium orthophosphates (CaPO4). This type of materials is of the
special significance for the human beings because they represent the inorganic
part of major normal (bones, teeth and antlers) and pathological (those appearing
due to various diseases) calcified tissues of mammals. For example,
atherosclerosis results in blood vessel blockage caused by a solid composite of
cholesterol with CaPO4, while dental caries (tooth decay) and osteoporosis (a low
bone mass with microarchitectural changes) mean a partial decalcification of
teeth and bones, respectively, that results in replacement of a less soluble and
harder biological apatite by more soluble and softer calcium
hydrogenorthophosphates. Due to the compositional similarities to the calcified
tissues of mammals, CaPO4 are widely used as biomaterials for bone grafting
purposes. In addition, CaPO4 have many other applications. Thus, there is a great
significance of CaPO4 for the humankind and, in this paper, an overview on the
current knowledge on this subject is provided.
PMID- 28501355
TI - Sono-photo-Fenton oxidation of bisphenol-A over a LaFeO3 perovskite catalyst.
AB - In this study, oxidation of bisphenol-A (IUPAC name - 2,2-(4,4-dihydroxyphenyl,
BPA), which is an endocrine disrupting phenolic compound used in the
polycarbonate plastic and epoxy resin industry, was investigated using sono-photo
Fenton process under visible light irradiation in the presence of an iron
containing perovskite catalyst, LaFeO3. The catalyst prepared by sol-gel method,
calcined at 500 degrees C showed a catalytic activity in BPA oxidation using sono
photo-Fenton process with a degradation degree and a chemical oxygen demand (COD)
reduction of 21.8% and 11.2%, respectively. Degradation of BPA was studied by
using individual and combined advanced oxidation techniques including sonication,
heterogeneous Fenton reaction and photo oxidation over this catalyst to
understand the effect of each process on degradation of BPA. It was seen, the
role of sonication was very important in hybrid sono-photo-Fenton process due to
the pyrolysis and sonoluminescence effects caused by ultrasonic irradiation. The
prepared LaFeO3 perovskite catalyst was a good sonocatalyst rather than a
photocatalyst. Sonication was not only the effective process to degrade BPA but
also it was the cost effective process in terms of energy consumption. The
studies show that the energy consumption is lower in the sono-Fenton process than
those in the photo-Fenton and sono-photo- Fenton processes.
PMID- 28501357
TI - Medicaid Reform: Key Considerations for Children's Health Care.
PMID- 28501358
TI - The Zero-LDL Hypothesis. Towards Extremely Low LDL Concentrations.
PMID- 28501356
TI - Engaging Overweight Adolescents in a Health and Fitness Program Using Wearable
Activity Trackers.
AB - INTRODUCTION: Our objectives were to (a) examine feasibility and receptivity of
overweight adolescents joining a community-based group fitness program and (b)
test preliminary efficacy of a 12-week pilot intervention designed to promote
health, fitness, and self-efficacy for the identified teens. METHODS: The 12-week
fitness program for overweight adolescents was developed and included planned
physical activities, nutrition classes, and goal-setting sessions. A one-group
pre-/posttest study design evaluated 20 participants from grades 10 through 12
who enrolled in the program pilot study. Participants were given a wearable
activity tracker that captured data using an Internet-based platform. Outcome
measures included body mass index, screen time, fitness, and cardiovascular
measures. RESULTS: A community fitness program for overweight adolescents was
successfully implemented. High school students were receptive to the intervention
and reported high program satisfaction. Positive effects included measurements of
strength, systolic blood pressure, weight, and screen time behaviors. DISCUSSION:
This study provides evidence to support the feasibility, acceptance, and
preliminary effects of the pilot program with overweight adolescents.
PMID- 28501359
TI - The Ebola epidemic in Liberia and managing the dead-A future role for
Humanitarian Forensic Action?
AB - With some of their economies, communities and health systems weakened by decades
of war and poor governance, it was no accident that an epidemic of Ebola virus
disease broke out in west Africa. Being spread in part by contact with body
fluids of those who had died from the disease, funerary rites and the way dead
bodies were managed were important modes of transmission. The Liberian Red Cross,
supported by the International Federation of Red Cross and Red Crescent Societies
and the International Committee of the Red Cross, undertook the challenging task
of managing the dead bodies in Monrovia during the epidemic. The work was
undertaken by volunteers, not health care workers, who were trained and equipped
for this task. The authors observed their work and were impressed. Valuable
lessons were learned for mortuaries generally, and for Humanitarian Forensic
Action involving the management of highly infectious human remains.
PMID- 28501360
TI - Cow urine, Indian yellow, and art forgeries: An update.
AB - In a recent technical note in this Journal, de Faria et al., 2017 [1] reported
the Raman spectrum of authentic Indian yellow artists' pigment, correcting a
decades old reference spectrum that has led to the misidentification of this
pigment in artworks that actually contained tartrazine yellow. The present
communication provides additional information and corrects important experimental
details mentioned by de Faria et al. that should lead to further identifications
of the authentic pigment in artworks. Despite their claim that the analysis of
this naturally fluorescent colorant is only possible with Fourier transform (FT)
instruments, the ready characterization of two authentic samples of historic
Indian yellow pigment is demonstrated here using commonly available visible and
near-infrared excitation sources on a dispersive Raman microspectrometer. To
highlight the importance of the proper identification of dyes and colorants, the
authentication and art historical implications of previous literature reports
that have misidentified Indian yellow on historic documents are more thoroughly
discussed here from a forensic science point of view. The numerous modern
pigments that are sold as imitation Indian yellow are addressed and analyzed,
allowing the ready noninvasive detection of anachronistic colorants in attempted
forgeries. Finally, this unusual pigment is positively identified for the first
time using non-invasive dispersive Raman microspectroscopy on a historic object
of uncertain date, a highly decorative manuscript from the Indian subcontinent.
PMID- 28501361
TI - Intrauterine insemination with gonadotropin stimulation or in vitro fertilization
for the treatment of unexplained subfertility: a randomized controlled trial.
AB - OBJECTIVE: To evaluate the best first line management option for the treatment of
unexplained subfertility-controlled ovarian hyperstimulation (COH) with
gonadotropins and IUI or IVF. DESIGN: Randomized controlled trial. SETTING:
Single center trial in a tertiary referral unit. PATIENT(S): Couples with
unexplained subfertility. INTERVENTION(S): Couples were randomized to receive
either three cycles of IUI + COH or one cycle of IVF. MAIN OUTCOME MEASURE(S):
Singleton pregnancy rate (PR) per couple. RESULT(S): A total of 207 couples were
randomly assigned to three cycles of IUI + COH (n = 101) or one cycle of IVF (n =
106). There were 25 (24.7%) singleton live births for the IUI + COH group and 33
(31.1%) for the IVF group (relative risk, 1.3; 95% confidence interval [CI] 0.81
1.96) with an absolute risk difference of 6.4% (95% CI -5.8% to 18.6%). The
multiple pregnancies per live birth were 4 (13.8%) for the IUI + COH group and 3
(8.3%) for the IVF group (relative risk, 0.6; 95% CI 0.14-2.4). There were no
cases of ovarian hyperstimulation syndrome (OHSS) in the IUI group and three
cases of OHSS (3.7%) in the IVF group. There were 17 live births from spontaneous
conception in between treatment cycles (8.2%). CONCLUSION(S): The singleton live
birth rate with one cycle of IVF was not significantly different than three
cycles of IUI + COH. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN43430382.
PMID- 28501363
TI - Sex and gender: you should know the difference.
PMID- 28501364
TI - Immune modulation treatments-where is the evidence?
AB - While advances in assisted reproductive techniques have been substantial, failure
of the apparently viable embryo to implant remains a source of distress and
frustration to patients and specialists alike. The unique maternal immunological
response to the embryo and the notion that defects in early placentation underlie
the great complications of pregnancy have focused attention on the therapeutic
potential of peri-implantation immunomodulation. On the face of it, the rationale
for this approach is very attractive. However, as will be argued in this review,
the clinical evidence base supporting the use of immunosuppressive treatments is
weak and difficult to apply in practice and fails the needs of both doctors and
their patients. This evidence gap is filled by justifications that are based
largely on meeting patient expectations and commercial imperatives. However, this
does not mean that immunomodulation treatments should be written off as
ineffective. The literature in this field, while suffering the same challenges of
heterogeneity, small studies, and publication bias as other areas of medicine,
does hint at the way forward. Recurrent implantation failure and pregnancy loss
are not diagnoses but clinical presentations that require appropriate phenotyping
and etiological investigation. We are increasingly gaining the tools to make an
"endometrial diagnosis," and these will allow us to design clinical studies of
interventions that treat the underlying cause rather than the symptoms of
implantation failure. The current evidence base does not support the clinical use
of immunomodulation therapies in patients undergoing IVF. However, more
discerning phenotyping may identify groups who could benefit.
PMID- 28501362
TI - Mode of conception does not appear to affect placental volume in the first
trimester.
AB - OBJECTIVE: To study whether infertility treatments, including IVF and non-IVF
fertility treatments, are associated with diseases of placental insufficiency in
early gestation. First trimester placental volumes by ultrasound and chorionic
villi weight during sampling (CVS) were performed to detect differences between
pregnancies conceived spontaneously versus with fertility treatments. DESIGN:
Retrospective cohort. SETTING: Academic tertiary center. PATIENT(S): Women with
singleton pregnancies undergoing CVS and first trimester ultrasound from April
2007 to November 2015. INTERVENTION(S): Estimated placental volume (EPV) was
calculated from ultrasound images using a validated computation and CVS estimated
tissue weight was performed using a validated visual analogue scale. MAIN OUTCOME
MEASURE(S): Adjusted linear regression was used to compare EPV and CVS weight
based on mode of conception. RESULT(S): A total of 1,977 spontaneous and 334
conceived with fertility treatments (133 non-IVF and 201 IVF) pregnancies were
included. Significant differences in maternal age, gravidity, hypertension, and
smoking status were identified. EPV and CVS weight were correlated with maternal
age, gestational age, and maternal hypertension. Adjusted linear regression
showed no difference in EPV in pregnancies conceived with fertility treatments
versus spontaneously. The CVS weight was significantly lower in the IVF
conceptions in unadjusted univariate analyses. However, after adjusted
regression, this was no longer significant. CONCLUSION(S): Mode of conception
does not appear to affect first trimester placental size. As differences in
maternal age, hypertension, and smoking status differ among the groups and are
correlated to placental size, it may be the underlying patient population leading
to abnormal placentation and insufficiency, not the fertility treatments used.
PMID- 28501365
TI - Why natural killer cells are not enough: a further understanding of killer
immunoglobulin-like receptor and human leukocyte antigen.
AB - The immune system's role in recurrent reproductive failure is a controversial
issue in assisted reproduction. Most studies into immune system implication in
reproduction have focused on finding markers of peripheral blood and less on the
uterine environment. Peripheral blood natural killer cells have become an "immune
study core" for women with recurrent miscarriage or recurrent implantation
failure, based on the mistaken notion that they cause reproductive failure by
killing or "rejecting" the embryo. Maternal-fetal tolerance begins at the uterine
level, so successful adaptation to the fetus occurs after a complicated process.
Insufficient uterine lining invasion by an invading extravillous trophoblast is
the primary defect in pregnancy disorders such as recurrent miscarriage. This
process is regulated by the interaction between maternal killer immunoglobulin
like receptors (KIRs), expressed by uterine natural killer cells (uNK), and their
ligand human leukocyte antigen (HLA) C, expressed by the extravillous
trophoblast. Pregnancies are an increased risk of disorders in mothers with KIR
AA when the fetus has paternal HLA-C2. A recent report has indicated that the
expression of more than one paternal HLA-C by the extravillous trophoblast in
assisted reproduction may affect placentation in mothers with KIR AA. This review
provides insight into the immune system's role in assisted reproductive
treatments. These insights can have an impact on the selection of single-embryo
transfer and/or oocyte/sperm donor according to HLA-C in patients with recurrent
implantation failure and recurrent miscarriage depending on their KIR haplotype.
PMID- 28501366
TI - Reproductive outcomes after a single dose of gonadotropin-releasing hormone
agonist compared with human chorionic gonadotropin for the induction of final
oocyte maturation in hyper-responder women aged 35-40 years.
AB - OBJECTIVE: To investigate the reproductive outcomes after the use of GnRH agonist
(GnRHa) compared with hCG for the induction of final oocyte maturation in GnRH
antagonist cycles performed in hyper-responder women aged 35-40 years. DESIGN:
Retrospective study. SETTING: Academic fertility center. PATIENT(S): Two hundred
seventy-two hyper-responder women aged 35-40 years who underwent controlled
ovarian stimulation under GnRH antagonist suppression were included. Final oocyte
maturation was performed with GnRHa (n = 168) or hCG (n = 104). Embryos were
cryopreserved at the blastocyst stage and transferred in subsequent warming
cycles (n = 542). Subjects were included in the analysis until live birth was
achieved, after which they were excluded from further analysis. INTERVENTION(S):
None. MAIN OUTCOME MEASURE(S): Cumulative live birth rate. RESULT(S): Subjects in
the GnRHa group achieved a higher number of oocytes (22 vs. 21) and a higher
number of mature oocytes (16 vs. 14). The number of cryopreserved blastocysts
(median of five blastocysts in both groups) was similar. Women in the hCG group
needed a lower number of warming cycles to achieve live birth (1.32 vs. 2.12),
had higher embryo implantation rates (48% vs. 39%), and the proportion of embryos
transferred until live birth was lower (33% vs. 57%). The cumulative live birth
rate was similar between the groups (48.15% vs. 48%). CONCLUSION(S): Although the
cumulative live birth rate is similar, a single dose of GnRHa possibly results in
suboptimal oocyte and embryo competence, as manifested by decreased embryo
implantation rates and increased time needed to achieve live birth.
PMID- 28501367
TI - Old habits die hard: retrospective analysis of outcomes with use of
corticosteroids and antibiotics before embryo transfer.
AB - OBJECTIVE: To evaluate clinical pregnancy rates in embryo transfer (ET) cycles
with and without peri-implantation corticosteroid and oral antibiotic
administration. DESIGN: Retrospective cohort study. SETTING: University
affiliated in vitro fertilization (IVF) clinic. PATIENT(S): Eight hundred and
seventy-six ETs with or without the routine use of methylprednisolone and
doxycycline. INTERVENTION(S): Embryo transfer procedures. MAIN OUTCOME
MEASURE(S): Clinical pregnancy rates (CPR). RESULT(S): The CPR with the routine
use of methylprednisolone and doxycycline was 56.1% compared with 61.5% after
discontinuation of these medications. Ongoing pregnancy rates were 49.5% with
medications versus 53.2% without medications. Of the cleavage-stage embryos, 79%
underwent assisted hatching; among these, the CPR was 28.7% when treated with
corticosteroids and antibiotics compared with 47.4% without medications.
CONCLUSION(S): No statistically significant difference in overall IVF outcomes
was noted after the discontinuation of routine peri-implantation corticosteroids
and antibiotics. The use of these medications varies across the country and may
be a result of habit rather than evidence-based medicine.
PMID- 28501368
TI - Contribution of immunology to implantation failure of euploid embryos.
AB - Outcomes in assisted reproduction have seen marked improvement. With increased
ability in the embryology laboratory to use extended embryo culture which in turn
enables other selective techniques, such as trophectoderm biopsy and
comprehensive chromosome screening, the chance of success per embryo transfer is
increased. However, even the selection of a euploid blastocyst, which selects out
many embryonic factors, does not yield successful implantation and ultimately
delivery in all cases. Among the factors that affect implantation failure of
apparently reproductively competent embryos, the immune system has been perhaps
both the most plausible and the most debated. There are data on T-helper cells,
in particular the TH1-TH2 balance, peripheral and uterine natural killer cells,
and autoantibodies, all of which have been shown to have variable effects on
implantation. Many investigators have developed and used a wide range of immune
tests and treatments aimed at manipulating the milieu to favor implantation.
Although it is certain that the immune system plays a role in implantation, our
understanding of the physiology, let alone the pathophysiology, remains
incomplete. It is imperative that we gain more clear evidence of causes and test
and implement treatment paradigms. In the meantime, immune testing or empirical
treatment with the use of immune modulators must be approached with caution.
PMID- 28501369
TI - Validation study of the SCREENIVF: an instrument to screen women or men on risk
for emotional maladjustment before the start of a fertility treatment.
AB - OBJECTIVE: To examine construct and criterion validity of the Dutch SCREENIVF
among women and men undergoing a fertility treatment. DESIGN: A prospective
longitudinal study nested in a randomized controlled trial. SETTING: University
hospital. PATIENT(S): Couples, 468 women and 383 men, undergoing an
IVF/intracytoplasmic sperm injection (ICSI) treatment in a fertility clinic,
completed the SCREENIVF. MAIN OUTCOME MEASURE(S): Construct and criteria validity
of the SCREENIVF. RESULT(S): The comparative fit index and root mean square error
of approximation for women and men show a good fit of the factor model. Across
time, the sensitivity for Hospital Anxiety and Depression Scale subscale in women
ranged from 61%-98%, specificity 53%-65%, predictive value of a positive test
(PVP) 13%-56%, predictive value of a negative test (PVN) 70%-99%. The sensitivity
scores for men ranged from 38%-100%, specificity 71%-75%, PVP 9%-27%, PVN 92%
100%. A prediction model revealed that for women 68.7% of the variance in the
Hospital Anxiety and Depression Scale on time 1 and 42.5% at time 2 and 38.9% at
time 3 was explained by the predictors, the sum score scales of the SCREENIVF.
For men, 58.1% of the variance in the Hospital Anxiety and Depression Scale on
time 1 and 46.5% at time 2 and 37.3% at time 3 was explained by the predictors,
the sum score scales of the SCREENIVF. CONCLUSION(S): The SCREENIVF has good
construct validity but the concurrent validity is better than the predictive
validity. SCREENIVF will be most effectively used in fertility clinics at the
start of treatment and should not be used as a predictive tool.
PMID- 28501370
TI - Gamete donation: current practices, public opinion, and unanswered questions.
PMID- 28501371
TI - Endometriosis on the uterosacral ligament: a marker of ureteral involvement.
AB - OBJECTIVE: To evaluate the association between ultrasound measurements of
endometriosis nodules on the uterosacral ligament (USL) and the risk of ureteral
involvement, as well as to assess whether associations with other ultrasound
variables increase the sensitivity and specificity of the diagnosis of ureteral
endometriosis. DESIGN: Cross-sectional, observational study. SETTING: University
hospital. PATIENT(S): Four hundred sixty-three women with deep infiltrating
endometriosis (DIE). INTERVENTION(S): Patients diagnosed with DIE underwent
transvaginal ultrasound endometriosis mapping before laparoscopic surgery for
full excision of endometriotic lesions. MAIN OUTCOME MEASURE(S): Preoperative
ultrasound evaluation, intra- and postoperative assessment, and anatomopathologic
confirmation. RESULT(S): Of the 463 patients who participated in the study, 111
(23.97%) presented with endometriosis nodules with USL involvement on ultrasound
examination conducted by a single radiologist. Receiver operating characteristic
curve analysis showed that the size of the USL nodule had a statistically
significant association with ipsilateral ureteral involvement. After multivariate
logistic regression, the variables reduction in ovarian mobility, ureteral
changes on the right side, size of the USL nodule, and presence of endometrioma
on the left side were significantly associated with a ureteral endometriosis
nodule. However, the combined result for the variables cited was worse than the
diagnostic analysis using only the size of the USL nodule. CONCLUSION(S):
Uterosacral ligament nodules with ultrasound measurements of 1.75 cm and 1.95 cm
on the right and left sides, respectively, significantly increase the risk of
ureteral involvement. Even with the association of other ultrasound variables,
there was no improvement in sensitivity. Therefore, USL nodule size is a key
measure for therapeutic planning and consent of the patient.
PMID- 28501372
TI - Exploring global recognition of quality midwifery education: Vision or fiction?
AB - BACKGROUND: Midwifery education is the foundation for preparing competent
midwives to provide a high standard of safe, evidence-based care for women and
their newborns. Global competencies and standards for midwifery education have
been defined as benchmarks for establishing quality midwifery education and
practice worldwide. However, wide variations in type and nature of midwifery
education programs exist. AIM: To explore and discuss the opportunities and
challenges of a global quality assurance process as a strategy to promote quality
midwifery education. DISCUSSION: Accreditation and recognition as two examples of
quality assurance processes in education are discussed. A global recognition
process, with its opportunities and challenges, is explored from the perspective
of four illustrative case studies from Ireland, Kosovo, Latin America and
Bangladesh. The discussion highlights that the establishment of a global
recognition process may assist in promoting quality of midwifery education
programs world-wide, but cannot take the place of formal national accreditation.
In addition, a recognition process will not be feasible for many institutions
without additional resources, such as financial support or competent evaluators.
In order to achieve quality midwifery education through a global recognition
process the authors present 5 Essential Challenges for Quality Midwifery
Education. CONCLUSION: Quality midwifery education is vital for establishing a
competent workforce, and improving maternal and newborn health. Defining a global
recognition process could be instrumental in moving toward this goal, but dealing
with the identified challenges will be essential.
PMID- 28501373
TI - Evaluating Appropriate Use of Pediatric Echocardiograms for Chest Pain in
Outpatient Clinics.
AB - BACKGROUND: Echocardiography is often used in the evaluation of pediatric chest
pain, but the incidence of cardiac pathology is low. In 2014, the American
College of Cardiology published appropriate use criteria (AUC) for
echocardiography including recommendations for pediatric chest pain. We evaluated
the frequency and diagnostic yield of echocardiograms performed for each AUC
indication and cost associated with echocardiograms performed for indications
meeting the "rarely appropriate" criteria. METHODS: Retrospective, single
institution study of all patients 18 years or younger undergoing an initial
evaluation for chest pain by a pediatric cardiologist (2014-15). We categorized
the appropriateness of indications for echocardiograms on the basis of the AUC.
We used multivariable logistic regression to determine factors associated with
performance of an echocardiogram with the "rarely appropriate" indication. Excess
costs associated with nondiagnostic echocardiograms meeting the "rarely
appropriate" criteria were estimated using the Healthcare Bluebook to estimate a
fair market price. RESULTS: The cohort included 539 patients, median age 13 years
(range, 3-18) and 51.0% female. With retrospective application of the AUC,
echocardiogram indications were classified as "appropriate" (304/539, 56.4%),
"maybe appropriate" (68/539, 12.6%), and "rarely appropriate" (167/539, 31.0%).
Echocardiograms were performed in 70.5% (380/539) of patients overall and in
35.9% (60/167) of patients with "rarely appropriate" indications. Of those
undergoing echocardiography, abnormal findings were present in 5.0% (19/380) and
incidental findings in 2.6% (10/380); however, only one echocardiogram (0.3%) led
to a diagnosis considered to be contributory to the patient's chest pain. There
were no abnormal findings in the "rarely appropriate" subgroup. Provider use of
echocardiography for "rarely appropriate" indications varied widely from 0 to 75%
across 15 providers (P = .004). In multivariable analysis, provider clinical
experience of >=20 years was associated with a lower rate of echocardiograms for
"rarely appropriate" indications (odds ratio, 0.21 [95% CI, 0.09-0.47] vs.
providers with <10 years' experience, P < .001). There was no significant
association between race, ethnicity, age, sex, payer status, or total number of
patients seen and performance of an echocardiogram meeting the "rarely
appropriate" indications. Echocardiograms with "rarely appropriate" indications
resulted in $47,578 in excess costs over the 1-year study. CONCLUSIONS:
Echocardiogram use in patients meeting the "rarely appropriate" indication
criteria is of little diagnostic utility and contributes to additional cost to
the patient and health care system.
PMID- 28501375
TI - Transthoracic Echocardiography versus Computed Tomography for Ascending Aortic
Measurements in Patients with Bicuspid Aortic Valve.
AB - BACKGROUND: Ascending aorta dilatation is common in bicuspid aortic valve (BAV).
The aim of this study was to investigate agreement of transthoracic
echocardiographic (TTE) measurement of the sinuses of Valsalva and the tubular
mid-ascending aorta (Asc-Ao) compared with electrocardiographically gated
computed tomographic angiographic (CTA) assessment in patients with BAV. METHODS:
Fifty-three patients with BAV (mean age, 54 +/- 14 years; 74% men) who underwent
both TTE and CTA imaging for ascending aortic assessment were retrospectively
identified. All studies were measured de novo by experts. TTE measurements were
obtained at the sinuses and the Asc-Ao, at both systole and end-diastole, using
both leading edge-to-leading edge (L-L) and inner edge-to-inner edge (I-I)
methods in the parasternal long-axis (LAX) view. The sinuses were also measured
in the parasternal short-axis (SAX) view using the same methods plus mid
diastole. CTA measurements were obtained in diastole using outer wall-to-outer
wall (O-O) and inner wall-to-inner wall (I-I) methods. Correlation and agreement
between the two imaging modalities were assessed using Lin correlation and Bland
Altman analysis, respectively. RESULTS: Compared with CTA O-O maximum sinuses
diameter, the best correlation and agreement were obtained using the TTE SAX mid
diastolic L-L method (rho = 0.89, 2.6 +/- 2.3 mm, respectively). Compared with
CTA O-O maximum Asc-Ao diameter, the TTE LAX systolic L-L method (rho = 0.93, 1.3
+/- 2.5 mm) was best. Compared with CTA I-I maximum sinuses diameter, the TTE SAX
mid-diastole L-L method (rho = 0.95, 0.6 +/- 2.2 mm) was unbiased. Compared with
CTA I-I maximum Asc-Ao diameter, the TTE LAX end-diastolic L-L method (rho =
0.95, 0.6 +/- 2.4 mm) was unbiased. CONCLUSIONS: In patients with BAV aortopathy,
unbiased agreement between CTA and TTE imaging can be obtained between the CTA I
I method and TTE SAX mid-diastolic L-L method for the sinuses and the TTE LAX end
diastolic L-L method for the Asc-Ao. When using the CTA O-O method, the best
agreement is obtained with the TTE SAX mid-diastolic L-L method for the sinuses
(bias ~2 mm) and the TTE LAX systolic L-L method (bias ~1 mm) for the Asc-Ao.
PMID- 28501374
TI - The Effect of the Superior Cavopulmonary Anastomosis on Ventricular Remodeling in
Infants with Single Ventricle.
AB - BACKGROUND: Infants with single ventricular physiology have volume and pressure
overload that adversely affect ventricular mechanics. The impact of superior
cavopulmonary anastomosis (SCPA) on single left ventricles versus single right
ventricles is not known. METHODS: As part of the Pediatric Heart Network placebo
controlled trial of enalapril in infants with single ventricular physiology,
echocardiograms were obtained before SCPA and at 14 months and analyzed in a core
laboratory. Retrospective analysis of the following measurements included single
ventricular end-diastolic volume (EDV), end-systolic volume (ESV), mass, mass-to
volume ratio (mass/volume), and ejection fraction. Qualitative assessment of
atrioventricular valve regurgitation and assessment of diastolic function were
also performed. RESULTS: A total of 156 participants underwent echocardiography
at both time points. Before SCPA, mean ESV and mass Z scores were elevated (3.4
+/- 3.7 and 4.2 +/- 2.9, respectively) as were mean EDV and mass/volume Z scores
(2.1 +/- 2.5 and 2.0 +/- 2.9, respectively). EDV, ESV, and mass decreased after
SCPA, but mass/volume and the degree of atrioventricular valve regurgitation did
not change. Subjects with morphologic left ventricles demonstrated greater
reductions in ventricular volumes and mass than those with right ventricles (mean
change in Z score: left ventricular [LV] EDV, -1.9 +/- 2.1; right ventricular
EDV, -0.7 +/- 2.5; LV ESV, -2.3 +/- 2.9; right ventricular ESV, -0.9 +/- 4.6; LV
mass, -2.5 +/- 2.8; right ventricular mass, -1.3 +/- 2.6; P <= .03 for all).
Approximately one third of patients whose diastolic function could be assessed
had abnormalities at each time point. CONCLUSIONS: Decreases in ventricular size
and mass occur in patients with single ventricle after SCPA, and the effect is
greater in those with LV morphology. The remodeling process resulted in
commensurate changes in ventricular mass and volume such that the mass/volume did
not change significantly in response to the volume-unloading surgery.
PMID- 28501376
TI - Six-Year Incidence of Age-Related Macular Degeneration in Asian Malays: The
Singapore Malay Eye Study.
AB - PURPOSE: To determine the 6-year incidence of early and late age-related macular
degeneration (AMD) in a Singaporean Malay population and to validate the Age
Related Eye Disease Study (AREDS) simplified severity scale in Asians. DESIGN:
Prospective, population cohort study. PARTICIPANTS: The Singapore Malay Eye Study
baseline participants (age, >=40 years; 2006-2008) were followed up in 2011
through 2013, and 1901 of 3280 of eligible participants (72.1%) took part.
METHODS: Fundus photographs were graded using the Wisconsin AMD grading system.
MAIN OUTCOME MEASURES: Incidence of early and late AMD. RESULTS: Gradable fundus
photographs were available for 1809 participants who attended both baseline and 6
year follow-up examinations. The age-standardized incidences of early and late
AMD were 5.89% (95% confidence interval [CI], 4.81-7.16) and 0.76% (95% CI, 0.42
1.29), respectively. The 5-year age-standardized incidence of early AMD
(calculated based on the 6-year incidence) was lower in our population (5.58%;
95% CI, 4.43-7.01) compared with the Beaver Dam Eye Study population (8.19%). The
incidence of late AMD in our population was similar to that of the Beaver Dam Eye
Study population (0.98% [95% CI, 0.49-1.86] vs. 0.91%), the Blue Mountains Eye
Study population (1.10% [95% CI, 0.52-9.56] vs. 1.10%), and the Hisayama Study
population (1.09% [95% CI, 0.54-4.25] vs. 0.84%). The incidence of late AMD
increased markedly with increasing baseline AREDS score (step 0, 0.23%; step 4,
9.09%). CONCLUSIONS: This study documented the incidence of early and late AMD in
a Malay population. The AREDS simplified severity scale is useful in predicting
the risk of late AMD development in Asians.
PMID- 28501378
TI - Incremental Revisions across the Life Span of Ophthalmic Devices after Initial
Food and Drug Administration Premarket Approval, 1979-2015.
AB - PURPOSE: To characterize the frequency, nature, and regulatory mechanisms by
which ophthalmic devices are iteratively modified after initial Food and Drug
Administration (FDA) Premarket Approval (PMA). DESIGN: Retrospective cross
sectional analysis using publicly available FDA data. PARTICIPANTS: Ophthalmic
devices initially approved via the FDA's PMA pathway between January 1, 1979 and
December 31, 2015. METHODS: We used the FDA's PMA Database to identify and
characterize initial approvals and subsequent postmarket modifications to Class
III ophthalmic devices. The FDA Recalls Database was used to identify associated
safety events. MAIN OUTCOME MEASURES: Median iterated life span (timespan across
which modifications occurred after initial PMA) and median number of supplements
approved per device, by device type, and overall, stratified by regulatory
pathway and modification type. RESULTS: Between 1979 and 2015, the FDA approved
168 original ophthalmic devices via the PMA pathway and 2813 subsequent
modifications. More than one third (n = 64; 38%) of original approvals were
intraocular lenses. Overall, devices underwent a median of 11 postmarket
modifications (interquartile range [IQR], 3-24.8) across a median 10.0-year
iterated life span (IQR, 4.1-16.7). The majority of devices (n = 144; 86%)
underwent more than 1 postapproval modification, including more than 1 design
modification (n = 84; 50%). The median number of changes altering device design
or labeling was 3.5 (IQR, 1-9). Although manufacturing alterations (n = 834 of
2813; 30%) were the most frequent type of revision, changes involving device
design (n = 667; 24%) and labeling (n = 417; 15%) were common. Recalled devices
underwent more frequent postapproval modifications per year (median, 1.4; IQR,
0.7-2.3; mean, 1.5; 95% confidence interval, 1.1-1.9) in the period preceding
recall than did nonrecalled devices (median, 0.5; IQR, 0.2-1.1; mean, 0.8; 95%
confidence interval, 0.7-1.0) across their market approval period (P < 0.001).
CONCLUSIONS: Most ophthalmic devices approved via the FDA's PMA pathway have
undergone extensive revisions, including serial design and labeling changes,
since their initial approvals, often without supporting clinical data.
Ophthalmologists should take into consideration that cumulative revisions may
render the clinical evidence that supported an original FDA approval less
relevant to newer device models.
PMID- 28501377
TI - Structural Changes Associated with Delayed Dark Adaptation in Age-Related Macular
Degeneration.
AB - PURPOSE: To examine the relationship between dark adaptation (DA) and optical
coherence tomography (OCT)-based macular morphology in age-related macular
degeneration (AMD). DESIGN: Prospective, cross-sectional study. PARTICIPANTS:
Patients with AMD and a comparison group (>50 years) without any vitreoretinal
disease. METHODS: All participants were imaged with spectral-domain OCT and color
fundus photographs, and then staged for AMD (Age-related Eye Disease Study
system). Both eyes were tested with the AdaptDx (MacuLogix, Middletown, PA) DA
extended protocol (20 minutes). A software program was developed to map the DA
testing spot (2 degrees circle, 5 degrees superior to the fovea) to the OCT B
scans. Two independent graders evaluated the B-scans within this testing spot, as
well as the entire macula, recording the presence of several AMD-associated
abnormalities. Multilevel mixed-effects models (accounting for correlated
outcomes between 2 eyes) were used for analyses. MAIN OUTCOME MEASURES: The
primary outcome was rod-intercept time (RIT), defined in minutes, as a continuous
variable. For subjects unable to reach RIT within the 20 minutes of testing, the
value of 20 was assigned. RESULTS: We included 137 eyes (n = 77 subjects), 72.3%
(n = 99 eyes) with AMD and the remainder belonging to the comparison group.
Multivariable analysis revealed that even after adjusting for age and AMD stage,
the presence of any abnormalities within the DA testing spot (beta = 4.8, P <
0.001), as well as any abnormalities in the macula (beta = 2.4, P = 0.047), were
significantly associated with delayed RITs and therefore impaired DA. In eyes
with no structural changes within the DA testing spot (n = 76, 55.5%), the
presence of any abnormalities in the remaining macula was still associated with
delayed RITs (beta = 2.00, P = 0.046). Presence of subretinal drusenoid deposits
and ellipsoid zone disruption were a consistent predictor of RIT, whether located
within the DA testing spot (P = 0.001 for both) or anywhere in the macula (P <
0.001 for both). Within the testing spot, the presence of classic drusen or
serous pigment epithelium detachment was also significantly associated with
impairments in DA (P <= 0.018). CONCLUSIONS: Our results suggest a significant
association between macular morphology evaluated by OCT and time to dark-adapt.
Subretinal drusenoid deposits and ellipsoid zone changes seem to be strongly
associated with impaired dark adaptation.
PMID- 28501379
TI - Metabolic impact of nutrient starvation in mevalonate-producing Escherichia coli.
AB - The aim of this work was to enhance mevalonate yield from glucose in Escherichia
coli by essential nutrient starvations and to reveal these effects on the central
carbon metabolism. Stationary phase culture without essential nutrients such as
nitrogen, sulfur, and magnesium was evaluated using an engineered E. coli
introducing mvaE and mvaS genes from Enterococcus faecalis. Sulfur starvation
resulted in the highest mevalonate yield of 0.61C-molC-mol-1 from glucose. The
metabolic impacts of nutrient starvation were investigated by 13C-metabolic flux
analysis. Under nitrogen starvation, the flux of the TCA cycle was large, causing
high CO2 production. This was caused by degradation of mevalonate synthesis
pathway enzymes. Under magnesium starvation, NADPH production was decreased,
which limited mevalonate synthesis and promoted an overflow of acetate. Sulfur
starvation not only suppressed the TCA cycle flux, but also supplied NADPH for
mevalonate synthesis.
PMID- 28501380
TI - CRISPRi mediated phosphoenolpyruvate carboxylase regulation to enhance the
production of lipid in Chlamydomonas reinhardtii.
AB - In this study, CRISPRi (clustered regularly interspaced short palindromic repeats
interference) was used for the first time to regulate expression of exogenously
supplied rfp gene as a proof-of-concept, and endogenous PEPC1 gene as a proof-of
function in Chlamydomonas reinhardtii. The efficiency of 94% and stability of 7
generations via CRISPRi mediated gene regulation in C. reinhardtii have been
demonstrated by RFP. Gene PEPC1 encoding proteins are essential for controlling
the carbon flux that enters the TCA cycle and plays a crucial role in carbon
partitioning of substrates in competition with lipid synthesis. All CrPEPC1 down
regulated strains have lower chlorophyll color, but higher biomass concentration
and lipid accumulation rate. The present results revealed that CRISPRi based
transcriptional silencing was applicable in C. reinhardtii and expanded the way
to improve the yield, titer and productivity of microalgae-based products.
PMID- 28501381
TI - Salinity induced oxidative stress alters the physiological responses and improves
the biofuel potential of green microalgae Acutodesmus dimorphus.
AB - The main aim of the present study was to analyze salinity stress induced
physiological and biochemical changes in a freshwater microalgae Acutodesmus
dimorphus. During single-stage cultivation, the accumulations of lipids and
carbohydrates increased with an increase in an initial salinity of the culture
medium. The carbohydrate and lipid accumulations of 53.30+/-2.76% and 33.40+/
2.29%, respectively, were observed in 200mM NaCl added culture. During two-stage
cultivation, salinity stress of 200mM was favorable for the growth up to 2days,
as suggested by higher biomass, lower levels of oxidative stress biomarkers and
no significant changes in the biochemical composition of the cells. Extending the
stress to 3days significantly increased the lipid accumulation by 43% without
affecting the biomass production. This study, thus, provides the strategy to
improve the biofuel potential of A. dimorphus along with presenting the
physiological adaptive mechanisms of a cell against salinity stress.
PMID- 28501382
TI - Fabrication of biochars obtained from valorization of biowaste and evaluation of
its physicochemical properties.
AB - This study investigated the yields and the physicochemical properties of biochar
from three different feedstocks viz., i) bioenergy byproducts (deoiled cakes of
Jatropha carcus and Pongamia glabra), ii) lignocellulose biomass (Jatropha carcus
seed cover), and iii) a noxious weed (Parthenium hysterophorus), obtained through
slow pyrolysis at a heating rate of 40 degrees Cmin-1 with a nitrogen flow
100mlmin-1 at a temperature range of 350-650 degrees C. For successful
utilization of biochar for C-sequestration, its ability to resist abiotic or
biotic degradation was deduced from recalcitrance index R50 by using TG analysis.
It was observed that the biochar produced at higher temperature had higher water
holding capacity (WHC) and pH, suggesting its suitability as an amendment in soil
with low water retention capacity; thus biochar may be designed to selectively
improve soil chemical and physical properties by altering feedstocks and
pyrolysis conditions. Biochar produced at 650 degrees C had highest yield in the
range of 28.52-39.9 wt.%.
PMID- 28501383
TI - Intentional Misuse and Abuse of Loperamide: A New Look at a Drug with "Low Abuse
Potential".
AB - BACKGROUND: Despite its opioid properties, loperamide has long been thought to
have low abuse potential due to its poor absorption from the gastrointestinal
tract and limited potential to cross the blood-brain barrier. A recent patient
reportedly taking loperamide to avoid heroin withdrawal symptoms, at doses
approximately 100 times those recommended, directed our attention to this issue.
OBJECTIVES: 1) Investigate number of cases of intentional loperamide abuse and
misuse reported to poison centers between 2009 and 2015; 2) Compile reports of
clinical effects of loperamide abuse; and 3) Search for evidence of increasing
Internet interest in the central opioid effects of loperamide. METHODS: For the
years 2009 thru 2015, we reviewed exposure calls related to misuse/abuse of
loperamide in the Texas Poison Center Network's database and the National Poison
Data System. We used Google trend analysis to detect evidence of increased
Internet interest in the illicit use of loperamide. RESULTS: Between 2009 and
2015, the number of misuse/abuse calls related to loperamide alone nearly
doubled, with about one-third of cases occurring in teens and young adults in
their 20s. Of particular concern are reports of significant cardiotoxic effects
(~18% of cases), including conduction defects and various dysrhythmias, sometimes
leading to death. Google Trends analysis demonstrates an increasing number of
searches for "loperamide high" and "loperamide withdrawal" beginning in 2011.
CONCLUSIONS: Loperamide misuse/abuse seems to be on the rise. Given its
propensity to induce conduction disturbances and dysrhythmias at very high doses,
emergency physicians should be vigilant for this form of drug abuse.
PMID- 28501384
TI - Acute Heart Failure in the Emergency Department: the SAFE-SIMEU Epidemiological
Study.
AB - BACKGROUND: Patients with acute heart failure (AHF) have high rates of attendance
to emergency departments (EDs), with significant health care costs. OBJECTIVES:
We aimed to describe the clinical characteristics of patients attending Italian
EDs for AHF and their diagnostic and therapeutic work-up. METHODS: We carried out
a retrospective analysis on 2683 cases observed in six Italian EDs for AHF
(January 2011 to June 2012). RESULTS: The median age of patients was 84 years
(interquartile range 12), with females accounting for 55.8% of cases (95%
confidence interval [CI] 53.5-57.6%). A first episode of AHF was recorded in
55.3% (95% CI 55.4-57.2%). Respiratory disease was the main precipitating factor
(approximately 30% of cases), and multiple comorbidities were recorded in > 50%
of cases (history of acute coronary syndrome, chronic obstructive pulmonary
disease, diabetes, chronic kidney disease, valvular heart disease). The treatment
was based on oxygen (69.7%; 67.9-71.5%), diuretics (69.2%; 67.9-71.5%),
nitroglycerin (19.7%; 18.3-21.4%), and noninvasive ventilation (15.2%; 13.8
16.6%). Death occurred within 6 h in 2.5% of cases (2.0-3.1%), 6.4% (5.5-7.3%)
were referred to the care of their general practitioners within a few hours from
ED attendance or after short-term (< 24 h) observation 13.9% (12.6-15.2%); 60.4%
(58.5-62.2%) were admitted to the hospital, and 16.8% (15.4-18.3%) were cared for
in intensive care units according to disease severity. CONCLUSIONS: Our study
reporting the "real-world" clinical activity indicates that subjects attending
the Italian EDs for AHF are rather different from those reported in international
registries. Subjects are older, with a higher proportion of females, and high
prevalence of cardiac and noncardiac comorbidities.
PMID- 28501385
TI - Full and Partial Thickness Burns from Spontaneous Combustion of E-Cigarette
Lithium-Ion Batteries with Review of Literature.
AB - BACKGROUND: In recent years, the use of electronic cigarettes (e-cigarettes) has
increased worldwide. Most electronic nicotine delivery systems use rechargeable
lithium-ion batteries, which are relatively safe, but in rare cases these
batteries can spontaneously combust, leading to serious full and partial
thickness burn injuries. Explosions from lithium-ion batteries can cause a flash
fire and accelerant-related burn injuries. CASE REPORT: A retrospective chart
review was conducted of 3 patients with lithium-ion battery burns seen at our
Level I community-based trauma center. Clinical presentation, management, and
outcome are presented. All 3 patients sustained burn injuries (total body surface
area range 5-13%) from the spontaneous combustion of lithium-ion batteries used
for e-cigarettes. All patients were treated with debridement and local wound
care. All fully recovered without sequelae. WHY SHOULD AN EMERGENCY PHYSICIAN BE
AWARE OF THIS?: Emergency physicians can expect to treat burn cases due to
spontaneous lithium-ion battery combustion as e-cigarette use continues to
increase. The cases presented here are intended to bring attention to lithium-ion
battery-related burns, prepare physicians for the clinical presentation of this
burn mechanism, and facilitate patient education to minimize burn risk.
PMID- 28501386
TI - Atrioesophageal Fistula after Ablation for Atrial Fibrillation.
AB - BACKGROUND: Atrioesophageal fistula (AEF) is a rare and highly fatal complication
of ablation procedures for atrial fibrillation. We report a diagnostically
challenging case of AEF that highlights the unfortunate outcome that can be
expected when this condition is not promptly diagnosed and managed accordingly.
The varied clinical presentations are reviewed and recommended diagnostic and
management approaches are presented. CASE REPORT: A 79-year-old female who was 5
weeks post-ablation presented to a community emergency department with chest pain
and a transient episode of left-arm weakness. Troponin was mildly elevated, but
other investigations, including thoracic and head computed tomography (CT) were
normal. During the course of the next few days in hospital, the diagnosis of AEF
became apparent, as the patient developed a fever and recurrent episodes of
neurologic deficits along with blood cultures that yielded upper gastrointestinal
flora. The patient was urgently transferred to a tertiary center where repeat
thoracic CT confirmed the diagnosis, but she succumbed to an intracranial bleed
before definitive surgical management could be performed. WHY SHOULD AN EMERGENCY
PHYSICIAN BE AWARE OF THIS?: This case is presented to increase awareness among
emergency physicians of this fatal condition that is increasing in incidence as
ablation procedures become more mainstream. The diagnosis can be challenging,
given that presenting symptoms are often variable and nonspecific. To complicate
matters further, performing certain diagnostic tests and interventions can prove
fatal in this particular patient population. Survival in these unfortunate cases
is highly dependent on initiating a prompt and appropriate diagnostic workup,
followed by rapid surgical intervention.
PMID- 28501387
TI - Surgical treatment of isolated zygomatic fracture: Outcome comparison between
titanium plate and bioabsorbable plate.
AB - BACKGROUND: Zygoma fracture is of clinical importance because malar prominence
plays an essential role in facial appearance. Traditionally, most maxillofacial
surgeons perform osteosynthesis with titanium plates and screws for rigid
fixation. However, this procedure has certain disadvantages that include the
possibility of implant exposure, palpability or loosening of the screws, painful
irritation, temperature sensitization, and radiographic artifacts. In this study,
we compared the function and satisfaction outcome between Bonamates(r)
bioabsorbable implant and Leibinger titanium implant. METHOD: Consecutively 53
patients with isolated unilateral zygomatic fracture that were treated with the
Bonamates(r) bioabsorbable plate system, n = 53 were compared to patients with
the titanium plate system, n = 55 in the period between 2009 and 2013. All
patients were followed-up at least 6 months. Preoperative and postoperative
facial computed tomography (CT) scans were performed and scored from 0 to 2 in
the 5 areas of zygoma. A score of 2 indicated the most severely displaced
fracture in one of the areas. A visual analogue scale ranging from 0 to 10 was
used to assess the postoperative aesthetic and functional satisfactions. RESULT:
The mean ages of the patients in the bioabsorbable and titanium plate groups were
33 years and 30 years, respectively. The male to female ratios were 1.2:1
(bioabsorbable plate group) and 1.1:1 (titanium plate group). The average
preoperative CT scan scores of the bioabsorbable and titanium plate groups were
5.7 and 5.1, respectively. The postoperative CT scan scores of the bioabsorbable
and titanium plate groups were 1.3 and 1.1, respectively. The implant cost of the
bioabsorbable group was approximately 6-fold higher than that of the titanium
plate group. The complication rate was similar in both groups and included
complications such as palpable implant, skin irritation, and hypersensitive
cheek. The patients in both groups attained similar mouth-opening function and a
satisfactory score at 6 months after operation. CONCLUSION: This study revealed
that the bioabsorbable plate outcome was similar to the titanium plate outcome
for patients with isolated unilateral zygomatic fracture. The bioabsorbable
implant system provides another option for internal fixation devices in the
treatment of zygomatic fractures and avoids implant removal surgery; however, the
implant cost of bioabsorbable plates is higher than that of titanium plates in
Taiwan.
PMID- 28501388
TI - Association between metabolic syndrome and chronic kidney disease in a Chinese
urban population.
AB - BACKGROUND: Few studies have examined the relationships between the prevalence of
chronic kidney disease (CKD) and the metabolic risk factors in a developing
country such as China, where genetic and environmental backgrounds differ from
those in Western countries. METHODS: The subjects of this cross-sectional study
were the individuals from 18 to 92y. The metabolic syndrome (MetS) was defined
based on the criteria of Adult Treatment Panel Third Report (ATP III), but using
body mass index (BMI) instead of waist circumference. CKD was defined as
decreased estimated glomerular filtration rate (eGFR<60mL/min/1.73m2) or presence
of proteinuria (urine protein>=1+) assessed using dipstick method. RESULTS: A
total of 26,601 subjects (average age of 48.7y) were analyzed. Among them, the
prevalence of the MetS and CKD was 36.4% and 3.0%, respectively. After adjustment
for age, gender, cigarette smoking and alcohol drinking, the prevalence of CKD
was significantly greater in subjects with than without MetS (OR 1.99, 95% CI
1.57-2.53, p<0.001). Multivariate-adjusted odd ratios for CKD in subjects with 3,
4 or 5 MetS components were 1.82 (95% CI 1.31-2.52, p<0.001), 2.92 (95% CI 2.09
4.09, p<0.001), and 3.07 (95% CI 1.67-5.67, p<0.001), respectively. After further
adjustments were made for the other components of MetS, only high fasting glucose
(OR 1.52, 95% CI 1.12-2.05) were significant risk factors for reduced renal
function(eGFR<60mL/min/1.73m2). High blood pressure (OR 1.81, 95% CI 1,42-2.29),
high triglycerides (OR 1.34, 95% CI 1.11-1.67) and high fasting glucose (OR 2.07,
95% CI 1.62-2.66) were significant risk factors for proteinuria. CONCLUSIONS:
MetS was highly prevalent in the middle-aged and elderly Chinese population in
the city of Jinan. There was a graded relationship between the number of MetS
components and risk of CKD. High fasting blood glucose levels were the main risk
factor of reduced renal function. High blood pressure, high fasting blood glucose
levels and high triglycerides were main risk factors for proteinuria.
PMID- 28501389
TI - Differential proteome profile in ischemic heart disease: Prognostic value in
chronic angina versus myocardial infarction. A proof of concept.
AB - The initial clinical manifestation of ischemic heart disease (IHD) i.e.
unheralded myocardial infarction (MI) versus chronic angina pectoris (AP) is
statistically associated with adverse or mild disease progression respectively in
the long-term follow-up. Here, we subjected AP and MI patients to blood proteomic
analysis by Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass
Spectrometry (SELDI-TOF-MS) in order to investigate putative new prognostic
biomarkers of IHD manifestation. We found several differentially expressed peaks
but four of them (4176, 4475, 14,158m/z and 8922m/z for AP and MI, respectively)
were most reliable. Two of them were identified; 14,158m/z peak was the double
charged form of Apolipoprotein A-I and its vasoprotective action accords with
prominence in AP. The 4176m/z peak was related to FAM83C protein, while neither
the 4475m/z peak nor the MI-linked 8922m/z peak could be identified. We conclude
that SELDI-TOF-MS analysis may yield a panel of molecular signals able to
retrospectively classify patients according to their clinical and molecular
features, exploitable for predicting the natural course of IHD.
PMID- 28501390
TI - Clinical Features and Incidence Rates of Ocular Complications in Patients With
Retinal Vasculitis.
AB - PURPOSE: To describe the incidence rates of visual loss and ocular complications
in patients with retinal vasculitis (RV). DESIGN: Retrospective cohort study.
METHODS: Clinical data were collected for 96 patients (175 eyes) diagnosed with
RV from 2003 to 2013. Main outcome measures included rates of visual loss and
ocular complications. Comparison of outcomes in patients with a relapsing vs
nonrelapsing disease also were analyzed. RESULTS: Over a median follow-up of 44
months (range: 1-153 months), the rate of visual loss to 20/50 or worse was 0.13
per eye-year (/EY, 95% confidence interval [CI], 0.09/EY to 0.18/EY) and to
20/200 or worse was 0.06/EY (95% CI, 0.04/EY to 0.08/EY). The most common
complications were cataract (0.31/EY), epiretinal membrane (0.16/EY), and
recurrent macular edema (0.09/EY). Patients with a relapsing course (median
number of relapses = 1, range: 1-6) appeared to have greater risk for visual loss
to 20/50 (odds ratio [OR] = 2.07; 95% CI, 0.88-4.90, P = .09) and 20/200 or worse
(OR = 2.49; 95% CI, 0.98-6.30, P = .05). Immunosuppressive drug therapy lowered
the risk of visual loss, independent of relapsing disease course (OR = 0.79; 95%
CI, 0.66-0.94, P = .01 and OR = 0.73; 95% CI, 0.57-0.93, P = .01 for the 20/50 or
worse and 20/200 or worse thresholds, respectively). CONCLUSIONS: Rates of visual
loss and complications among patients with RV were similar to reported rates in
noninfectious uveitides. Treatment with immunosuppressive drugs lowered the risk
of visual loss. A relapsing course suggested an increased risk for visual loss
but was not statistically significant, perhaps owing to low numbers of
recurrences.
PMID- 28501391
TI - Long-term Visual Acuity, Strabismus, and Nystagmus Outcomes Following
Multimodality Treatment in Group D Retinoblastoma Eyes.
AB - PURPOSE: To analyze the long-term visual acuity, strabismus, and nystagmus
outcomes in Group D retinoblastoma following multimodality treatments in a
national retinoblastoma referral center. DESIGN: Retrospective interventional
case series. METHODS: A 13-year retrospective chart review of Group D eyes
treated initially with intravenous chemotherapy (IVC) and followed up for at
least 1 year from last treatment. Risk factors for final visual acuity (VA) were
analyzed, and rate of strabismus and nystagmus at last follow-up visit were
calculated. RESULTS: One hundred and four Group D eyes (92 patients) presented to
our center during the study period, of which 32 (27 patients) met the inclusion
criteria. Following IVC (vincristine, etoposide, and carboplatin), adjuvant
treatments included intraophthalmic artery chemotherapy in 5 (16%) eyes, plaque
brachytherapy in 5 (16%), transpupillary thermotherapy (TTT) in 18 (56%), and
cryotherapy in 24 (75%) eyes. On last examination, 64.41 +/- 6.76 months from
presentation, mean final VA was 20/283 (logMAR equivalent of 1.15 +/- 0.15). On
univariate analysis, presentation age, foveal retinoblastoma (at initial
examination), use of TTT, and tumor-foveola distance (at last visit) were found
to be significant risk factors for worse VA (P < .026). On multivariate analysis,
however, only TTT was found to be significant (P = .010). At last visit, 6 of 27
(22%) patients had nystagmus and 12 of 20 (60%) bilaterally salvaged patients had
strabismus (n = 10 exotropia and n = 2 esotropia). CONCLUSIONS: After
multimodality treatments initiated with IVC, 50% of salvaged Group D
retinoblastoma eyes had <20/200 vision, with TTT being a risk factor for worse
vision; 60% had strabismus; and 22% had nystagmus.
PMID- 28501392
TI - Acute Retinal Necrosis: Presenting Characteristics and Clinical Outcomes in a
Cohort of Polymerase Chain Reaction-Positive Patients.
AB - PURPOSE: To identify determinants of adverse outcomes in acute retinal necrosis
(ARN), presenting characteristics and incidence rates of vision loss and ocular
complications in a cohort of polymerase chain reaction (PCR)-positive eyes were
analyzed. DESIGN: Retrospective observational cohort study. METHODS: Forty-one
eyes of 36 patients with clinically diagnosed ARN, PCR-positive for herpes
simplex virus or varicella zoster virus and evaluated between January 2002 and
June 2013, were included. Main outcome measures included incidence rates of
vision loss and retinal detachment (RD). RESULTS: Presenting visual acuity was
generally poor (20/50 to >20/200 in 27%; 20/200 or worse in 56%). The incidence
rate of <=20/200 was 0.66/eye-year (EY), (95% confidence interval [CI], 0.32/EY
to 1.22/EY); the rate of light perception or no light perception vision was
0.07/EY (95% CI, 0.02/EY to 0.16/EY). During follow-up, 59% of eyes developed at
least 1 RD (rate = 0.40/EY, 95% CI, 0.19/EY to 0.58/EY). Eyes with retinitis
involving >=25% of the retina at presentation detached at nearly 12 times the
rate, as compared to those with <25% retinal involvement (0.70/EY vs 0.06/EY; P =
.001). Development of an RD was the greatest determinant of adverse visual
outcomes, with 4% of eyes, that had experienced at least 1 RD, achieving a best
corrected visual acuity of >=20/40 compared to 53% of eyes that never detached (P
= .0003). CONCLUSIONS: Poor outcomes in ARN were common in this cohort. RD
confers the greatest risk of incident vision loss, and once 25% or more of the
retina is involved the risk of RD and visual loss increases significantly.
PMID- 28501393
TI - Seq-ing the Circuit Logic of the Basal Ganglia.
AB - Recently, Wallace et al. (2017) provide an unprecedented view of the layers of
molecular, cellular and circuit complexity involving a basal ganglia output
structure, the entopeduncular nucleus. Their findings lend order to chaos by
revealing how molecularly and functionally defined cellular subsets are organized
into distinct circuitry.
PMID- 28501394
TI - [Changes in hazardous drinking in Spanish adolescent population in the last
decade (2004-2013) using a quantitative and qualitative design].
AB - OBJECTIVE: To determine the changes in hazardous drinking in adolescents in the
last decade, as well as their motivations and experiences. DESIGN: Firstly, a
descriptive design using a self-report questionnaire, and secondly an explanatory
qualitative design, with video recordings of discussion groups with content
analysis (coding, triangulation of categories and verification of results).
SETTING AND PARTICIPANTS: Pupils from an urban High School, administering a
questionnaire every 3 years from 2004 to 2013. Purposive sampling was used to
elect groups in qualitative design. Homogeneity criteria: education level;
heterogeneity criteria: age, gender, and drug use. MAIN MEASUREMENTS:
Questionnaire: age, gender, drug use, and the CAGE test. Interviews: semi
structured on a previous script, evaluating experiences and expectations.
RESULTS: Descriptive design: A total of 1,558 questionnaires, age 14.2+/
0.3years, 50% female. The prevalence of alcohol drinking decreases (13%), but its
hazardous use increases (11%; P<.001, chi2). This is associated with being female
(P<.01 chi2), higher alcohol consumption (>6 standard drink units weekly; P<.001,
ANOVA), during the weekend (56%; P<.01, chi2) and multiple drug use (P<.01,
chi2). CAGE questionnaire: 37% >=1positive response (related to hazardous
drinking, P<.05 chi2), 18% >=2answers. QUALITATIVE: A total of 48 respondents,
classified into 4 categories: personal factors (age, gender), social influences
(family, friends), consumption standards (accessibility, nightlife), and
addiction (risk, multiple drug use). CONCLUSION: Despite the decrease in the
prevalence of alcohol drinking, the increase in the percentage of the hazardous
drinking is a public health problem. It is related to being female, binge
drinking, and multiple drug use. Nightlife and social standards are the main
reasons given by adolescents, who have no perception of risk.
PMID- 28501395
TI - [Acceptability and feasibility among primary care doctors of the opportunistic
search for HIV in Health Care centers in Spain].
AB - OBJECTIVE: To evaluate the acceptability and feasibility of the opportunistic
search of HIV according to primary care doctors' experience. To set up the
profile of the physician involved in this study. DESIGN: Observational,
transversal study. LOCATION: Primary Care Centers of the National Health System.
PARTICIPANTS: General practitioners and residents who participated in VIH-AP
study to measure the acceptability of HIV opportunistic search by patients. MAIN
MEASUREMENTS: Self-filling survey to collect data on age, sex, teaching skills,
amount of years dedicated to research, time working with the same quota of
patients, acceptability and feasibility of opportunistic HIV search. RESULTS: A
total of 197 physicians with a mean age of 45.2+/-9.7 (SD) years. 18.8% were
under 36years old, 70.1% were women and 62.4% had teaching skills. 55.8% worked
in towns with a population over 100,000 inhabitants and the mean of years working
with the same quota of patients was 6.4+/-6.6. 91.9% (95%CI: 88.1-98.7) of them
considered the opportunistic search of HIV acceptable and 89.3% (95%CI: 85.0
93.6), feasible to perform. The multivariate analysis showed positive relation
between the acceptability/feasibility and teaching skills (OR: 2.74; 95%CI: 1.16
6.49). The acceptance of the screening by patients was 93.1% and this was
positively related to how long the doctor had worked with the same quota,
teaching skills and the amount of years dedicated to research. CONCLUSIONS: HIV
opportunistic search is an acceptable and feasible method for primary care
professionals.
PMID- 28501396
TI - Analysis of copy number variations in Holstein-Friesian cow genomes based on
whole-genome sequence data.
AB - Thirty-two whole genome DNA sequences of cows were analyzed to evaluate inter
individual variability in the distribution and length of copy number variations
(CNV) and to functionally annotate CNV breakpoints. The total number of deletions
per individual varied between 9,731 and 15,051, whereas the number of
duplications was between 1,694 and 5,187. Most of the deletions (81%) and
duplications (86%) were unique to a single cow. No relation between the pattern
of variant sharing and a family relationship or disease status was found. The
animal-averaged length of deletions was from 5,234 to 9,145 bp and the average
length of duplications was between 7,254 and 8,843 bp. Highly significant inter
individual variation in length and number of CNV was detected for both deletions
and duplications. The majority of deletion and duplication breakpoints were
located in intergenic regions and introns, whereas fewer were identified in
noncoding transcripts and splice regions. Only 1.35 and 0.79% of the deletion and
duplication breakpoints were observed within coding regions. A gene with the
highest number of deletion breakpoints codes for protein kinase cGMP-dependent
type I, whereas the T-cell receptor alpha constant gene had the most duplication
breakpoints. The functional annotation of genes with the largest incidence of
deletion/duplication breakpoints identified 87/112 Kyoto Encyclopedia of Genes
and Genomes pathways, but none of the pathways were significantly enriched or
depleted with breakpoints. The analysis of Gene Ontology (GO) terms revealed that
a cluster with the highest enrichment score among genes with many deletion
breakpoints was represented by GO terms related to ion transport, whereas the GO
term cluster mostly enriched among the genes with many duplication breakpoints
was related to binding of macromolecules. Furthermore, when considering the
number of deletion breakpoints per gene functional category, no significant
differences were observed between the "housekeeping" and "strong selection"
categories, but genes representing the "low selection pressure" group showed a
significantly higher number of breakpoints.
PMID- 28501397
TI - Effect of conjugated linoleic acid and acetate on milk fat synthesis and adipose
lipogenesis in lactating dairy cows.
AB - During biohydrogenation-induced milk fat depression (MFD), nutrients are spared
from milk fat synthesis and are available for other metabolic uses. Acetate is
the major carbon source spared and it may increase lipid synthesis in adipose
tissue during MFD. The objective of this study was to compare the effect of trans
10,cis-12 conjugated linoleic acid (CLA) and the amount of acetate spared during
CLA-induced MFD on adipose tissue lipogenesis. Nine multiparous, lactating,
ruminally cannulated Holstein cows (244 +/- 107 d in milk; 25 +/- 8.4 kg of
milk/d; mean +/- standard deviation) were randomly assigned to treatments in a 3
* 3 Latin square design. Experimental periods were 4 d followed by a 10-d
washout. Treatments were control (CON), ruminal infusion of acetate (AC;
continuous infusion of 7 mol/d adjusted to pH 6.1 with sodium hydroxide), or
abomasal infusion of CLA (10 g/d of both trans-10,cis-12 CLA and cis-9,trans-11
CLA). Dry matter intake, milk yield, and milk protein yield and percentage were
not affected by treatments. Compared with CON, milk fat yield decreased 23% and
fat percent decreased 28% in CLA, and milk fat yield increased 20% in AC.
Concentration and yield of milk de novo synthesized fatty acids (C16) was increased by CLA,
compared with CON. Yield of de novo synthesized fatty acids and palmitic acid was
increased by AC, compared with CON. Lipogenesis capacity of adipose tissue
explants was decreased 72% by CLA, but was not affected by AC. Acetate oxidation
by adipose explants was not affected by treatments. Treatments had no effect on
expression of key lipogenic factors, lipogenic enzymes, and leptin; however,
expression of fatty acid binding protein 4 was reduced in CLA compared with CON.
Additionally, hormone-sensitive lipase and perilipin 1 were decreased by CLA and
acetate. Plasma glucose and glucagon concentrations were not affected by
treatments; however, CLA increased nonesterified fatty acids 17.7%, beta
hydroxybutyrate 16.1%, and insulin 27.8% compared with CON, and AC increased
plasma beta-hydroxybutyrate 18%. In conclusion, during CLA-induced MFD in low
producing cow adipose tissue was sensitive to the anti-lipogenic effects of CLA,
while spared acetate did not stimulate adipose lipogenesis. However, acetate may
play an important role in stimulating lipogenesis and improving energy status in
the mammary gland under normal conditions.
PMID- 28501398
TI - Machine-learning-based calving prediction from activity, lying, and ruminating
behaviors in dairy cattle.
AB - The objective of this study was to use automated activity, lying, and rumination
monitors to characterize prepartum behavior and predict calving in dairy cattle.
Data were collected from 20 primiparous and 33 multiparous Holstein dairy cattle
from September 2011 to May 2013 at the University of Kentucky Coldstream Dairy.
The HR Tag (SCR Engineers Ltd., Netanya, Israel) automatically collected neck
activity and rumination data in 2-h increments. The IceQube (IceRobotics Ltd.,
South Queensferry, United Kingdom) automatically collected number of steps, lying
time, standing time, number of transitions from standing to lying (lying bouts),
and total motion, summed in 15-min increments. IceQube data were summed in 2-h
increments to match HR Tag data. All behavioral data were collected for 14 d
before the predicted calving date. Retrospective data analysis was performed
using mixed linear models to examine behavioral changes by day in the 14 d before
calving. Bihourly behavioral differences from baseline values over the 14 d
before calving were also evaluated using mixed linear models. Changes in daily
rumination time, total motion, lying time, and lying bouts occurred in the 14 d
before calving. In the bihourly analysis, extreme values for all behaviors
occurred in the final 24 h, indicating that the monitored behaviors may be useful
in calving prediction. To determine whether technologies were useful at
predicting calving, random forest, linear discriminant analysis, and neural
network machine-learning techniques were constructed and implemented using R
version 3.1.0 (R Foundation for Statistical Computing, Vienna, Austria). These
methods were used on variables from each technology and all combined variables
from both technologies. A neural network analysis that combined variables from
both technologies at the daily level yielded 100.0% sensitivity and 86.8%
specificity. A neural network analysis that combined variables from both
technologies in bihourly increments was used to identify 2-h periods in the 8 h
before calving with 82.8% sensitivity and 80.4% specificity. Changes in behavior
and machine-learning alerts indicate that commercially marketed behavioral
monitors may have calving prediction potential.
PMID- 28501399
TI - Effect of feeding strategies and cropping systems on greenhouse gas emission from
Wisconsin certified organic dairy farms.
AB - Organic agriculture continues to expand in the United States, both in total
hectares and market share. However, management practices used by dairy organic
producers, and their resulting environmental impacts, vary across farms. This
study used a partial life cycle assessment approach to estimate the effect of
different feeding strategies and associated crop production on greenhouse gas
emissions (GHG) from Wisconsin certified organic dairy farms. Field and livestock
driven emissions were calculated using 2 data sets. One was a 20-yr data set from
the Wisconsin Integrated Cropping System Trial documenting management inputs,
crop and pasture yields, and soil characteristics, used to estimate field-level
emissions from land associated with feed production (row crop and pasture),
including N2O and soil carbon sequestration. The other was a data set summarizing
organic farm management in Wisconsin, which was used to estimate replacement
heifer emission (CO2 equivalents), enteric methane (CH4), and manure management
(N2O and CH4). Three combinations of corn grain (CG) and soybean (SB) as
concentrate (all corn = 100% CG; baseline = 75% CG + 25% SB; half corn = 50% CG +
50% SB) were assigned to each of 4 representative management strategies as
determined by survey data. Overall, GHG emissions associated with crop production
was 1,297 +/- 136 kg of CO2 equivalents/t of ECM without accounting for soil
carbon changes (DeltaSC), and GHG emission with DeltaSC was 1,457 +/- 111 kg of
CO2 equivalents/t of ECM, with greater reliance on pasture resulting in less
DeltaSC. Higher levels of milk production were a major driver associated with
reduction in GHG emission per metric tonne of ECM. Emissions per metric tonne of
ECM increased with increasing proportion of SB in the ration; however, including
SB in the crop rotation decreased N2O emission per metric tonne of ECM from
cropland due to lower applications of organically approved N fertility inputs.
More SB at the expense of CG in the ration reduced enteric CH4 emission per
metric tonne of ECM (because of greater dietary fat content) but increased N2O
emission per metric tonne of ECM from manure (because of greater N content). An
increased reliance on pasture for feed at the expense of grain resulted in
decreased in milk production, subsequently leading to substantially higher
emissions per metric tonne of ECM.
PMID- 28501400
TI - The genetics of antibody response to paratuberculosis in dairy cattle.
AB - Genetic parameters were estimated for antibody response to paratuberculosis
(Mycobacterium avium ssp. paratuberculosis) using milk ELISA test results,
collected and analyzed by National Milk Records, from Holstein Friesian cows on
UK dairy farms in their first 3 lactations. Milk ELISA test results were obtained
from 2007 to 2012 and combined with milk recording data and pedigree information.
The reduced data set edited for the purposes of genetic parameter estimation
consisted of 148,054 milk ELISA records from 64,645 lactations in 40,142 cows of
908 sires, recorded in 641 herds. Milk ELISA test results were loge-transformed
and univariate analysis of 3 alternative animal models and equivalent sire models
were considered. The most appropriate model included additive genetic and
permanent environmental random effects, whereas maternal effects were significant
according to likelihood ratio test and Akaike's information criterion but not for
Bayesian information criterion. Heritability and repeatability estimates were
0.06 and 0.37, respectively, for the chosen animal model and its equivalent sire
model. A subset of the data including herds with greater than 10% positive tests
gave a slightly higher heritability of 0.08. Favorable but generally low
significant genetic correlations were obtained between antibody response with 305
d milk yield (-0.16), 305-d protein yield (-0.16), loge-transformed lactation
average somatic cell count (0.15), and the number of mastitis episodes (0.22).
Thus, selection on the antibody response to paratuberculosis, should not be
detrimental to production or udder health traits. Testing cattle for
paratuberculosis is important for its use in control programs and although the
heritability of antibody response was low, breeding against the disease might be
a good prospect as a preventative measure to assist together with other
approaches in an overall control strategy.
PMID- 28501401
TI - Milk production and composition, nitrogen utilization, and grazing behavior of
late-lactation dairy cows as affected by time of allocation of a fresh strip of
pasture.
AB - Eighty late-lactation dairy cows were used to examine the effects of allocating a
new pasture strip of a sward based on ryegrass (Lolium perenne L.) in the morning
(a.m.; ~0730 h) or in the afternoon (p.m.; ~1530 h) on milk production and
composition, nitrogen (N) utilization, and grazing behavior. Cows grazed the same
pasture strips for 24 h and were offered the same daily herbage allowance.
Herbage composition differed among treatments; p.m. herbage had greater dry
matter (DM; 22.7 vs. 19.9%), organic matter (OM; 89.5 vs. 88.9%), and water
soluble carbohydrate (10.9 vs. 7.6%) concentrations and lesser crude protein
(20.5 vs. 22.2%) and neutral detergent fiber (48.8 vs. 50.4%) concentrations
compared with a.m. herbage. Total fatty acids (FA), alpha-linolenic acid, and
polyunsaturated FA (PUFA) were greater in a.m. herbage, whereas monounsaturated
FA were greater in p.m. herbage. Estimates of herbage DM intake did not differ
among treatments. Daily milk yields and milk fat and milk protein concentrations
were similar among treatments, whereas milk fat (684 vs. 627 g/cow), milk protein
(545 vs. 505 g/cow), and milk solids (milk fat + milk protein) yields (1,228 vs.
1,132 g/cow) tended to be greater for cows on p.m. herbage. Rumenic acid and
total PUFA in milk were greater for cows on a.m. herbage, whereas oleic acid was
greater for cows on p.m. herbage. Estimates of urinary N excretion (g/d) did not
differ among treatments, but urinary N concentrations were greater for cows on
a.m. herbage (5.85 vs. 5.36 g/L). Initial herbage mass (HM) available (kg of
DM/ha) and instantaneous HM disappearance rates (kg of DM/ha and kg of DM/h) did
not differ, but fractional disappearance rates (0.56 vs. 0.74 per hour for a.m.
vs. p.m., respectively) differed. Under the current conditions, timing of pasture
strip allocation altered the herbage nutrient supply to cows; allocating a fresh
strip of pasture later in the day resulted in moderate increases in milk and milk
solids yields in late-lactation dairy cows. Conversely, a greater concentration
of precursor FA in a.m. herbage resulted in a greater concentration of beneficial
FA in milk, compared with cows on p.m. herbage.
PMID- 28501402
TI - Thiamine supplementation facilitates thiamine transporter expression in the rumen
epithelium and attenuates high-grain-induced inflammation in low-yielding dairy
cows.
AB - An experiment was conducted to uncover the effects of increasing dietary grain
levels on expression of thiamine transporters in ruminal epithelium, and to
assess the protective effects of thiamine against high-grain-induced inflammation
in dairy cows. Six rumen-fistulated, lactating Holstein dairy cows (627 +/- 16.9
kg of body weight, 180 +/- 6 d in milk; mean +/- standard deviation) were
randomly assigned to a replicated 3 * 3 Latin square design trial. Three
treatments were control (20% dietary starch, dry matter basis), high-grain diet
(HG, 33.2% dietary starch, DM basis), and HG diet supplemented with 180 mg of
thiamine/kg of dry matter intake. On d 19 and 20 of each period, milk performance
was measured. On d 21, ruminal pH, endotoxic lipopolysaccharide (LPS), and
thiamine contents in rumen and blood, and plasma inflammatory cytokines were
detected; a rumen papillae biopsy was taken on d 21 to determine the gene and
protein expression of toll-like receptor 4 (TLR4) signaling pathways. The HG diet
decreased ruminal pH (5.93 vs. 6.49), increased milk yield from 17.9 to 20.2
kg/d, and lowered milk fat and protein from 4.28 to 3.83%, and from 3.38 to
3.11%, respectively. The HG feeding reduced thiamine content in rumen (2.89 vs.
8.97 MUg/L) and blood (11.66 vs. 17.63 MUg/L), and the relative expression value
of thiamine transporter-2 (0.37-fold) and mitochondrial thiamine pyrophosphate
transporter (0.33-fold) was downregulated by HG feeding. The HG-fed cows
exhibited higher endotoxin LPS in rumen fluid (134,380 vs. 11,815 endotoxin
units/mL), and higher plasma concentrations of lipopolysaccharide binding protein
and pro-inflammatory cytokines when compared with the control group. The gene and
protein expression of tumor necrosis factor alpha (TNFalpha), IL1B, and IL6 in
rumen epithelium increased when cows were fed the HG diet, indicating that local
inflammation occurred. The depressions in ruminal pH, milk fat, and protein of HG
fed cows were reversed by thiamine supplementation. Thiamine supplementation
increased thiamine contents in rumen and blood, and also upregulated the relative
expression of thiamine transporters compared with the HG group. Thiamine
supplementation decreased ruminal LPS (49,361 vs. 134,380 endotoxin units/mL) and
attenuated the HG-induced inflammation response as indicated by a reduction in
plasma IL6, and decreasing gene and protein expression of pro-inflammatory
cytokines in rumen epithelium. Western bottling analysis showed that thiamine
suppressed the protein expression of TLR4 and the phosphorylation of nuclear
factor kappa B (NFkappaB) unit p65. In conclusion, HG feeding inhibits thiamine
transporter expression in ruminal epithelium. Thiamine could attenuate the
epithelial inflammation during high-grain feeding, and the protective effects may
be due to its ability to suppress TLR4-mediated NFkappaB signaling pathways.
PMID- 28501404
TI - Effects of dietary crude protein concentration on late-lactation dairy cow
performance and indicators of nitrogen utilization.
AB - The objectives of this study were to measure performance responses and to
evaluate indictors of N utilization in late-lactation cows fed diets with
incremental reductions in crude protein (CP) concentration. Holstein cows (n =
128; 224 +/- 54 d in milk) were stratified by parity and days pregnant (86 +/- 25
d) and randomly assigned to 1 of 16 pens in a randomized complete block design.
For 3 wk, all cows received a covariate diet containing 16.9% CP [dry matter (DM)
basis]. For the subsequent 12 wk, pens were randomly assigned to 1 of 4
treatments that contained 16.2, 14.4, 13.1, or 11.8% CP (DM basis). Diets were
offered once daily and contained 32.5% corn silage, 32.5% alfalfa silage, 13.5%
high-moisture corn, and 21.5% concentrate mix. A reduction in dietary CP was
achieved by replacing soybean meal with soy hulls in the concentrate mix (DM
basis). Dry matter intake, milk urea N (MUN; mg/dL), and the yield of milk urea N
(g/d) decreased linearly with dietary CP. Compared with a 16.2% CP diet, a 14.4%
CP diet did not alter milk yield throughout the study, but the 13.1 and 11.8% CP
diets reduced milk yield after 4 and 1 wk, respectively. Furthermore, milk
protein percentage was reduced for all dietary CP less than 16.2%, but this
negative effect was temporary and disappeared after 7 wk for the 14.4% CP diet.
In contrast, MUN adjusted to a new steady state within 1 wk for all dietary
treatments. Modeling quadratic responses with a plateau led to predictions of no
reduction in fat- and protein-corrected milk (32.6 kg/d) and yields of fat (1.31
kg/d), lactose (1.49 kg/d), and true protein (1.12 kg/d) until dietary CP
decreased below 15.5, 15.3, 15.9, and 16.2%, respectively. In this study, MUN and
the yield of MUN were highly correlated with N intake, milk protein yield, and
fat- and protein-corrected milk. Surprisingly, N use efficiency (milk protein
N/intake N) was not correlated with any variables related to N utilization and
reached an apparent upper limit of approximately 30%. Although this observation
may be associated with feeding diets deficient in metabolizable protein, late
lactation cows in this study adjusted to low dietary CP concentration better than
anticipated as milk production was 2.6, 3.6, 6.4, and 8.0 kg/d higher than
National Research Council (2001)-predicted metabolizable protein-allowable milk
for dietary CP of 16.2, 14.4, 13.1, and 11.8%, respectively.
PMID- 28501403
TI - Use of calcitriol to maintain postpartum blood calcium and improve immune
function in dairy cows.
AB - Our objectives were to determine the effects of an injectable formulation of
calcitriol on mineral metabolism and immune function in postpartum Holstein cows
that received an acidogenic diet prepartum to minimize hypocalcemia. In
experiment 1, cows within 6 h of calving received calcitriol (0, 200, or 300 MUg)
to determine the dose needed to increase plasma concentrations of Ca; 300 MUg was
sufficient to sustain Ca for at least 3 d. In experiment 2, multiparous cows were
assigned randomly to receive only vehicle (control, n = 25) or 300 MUg of
calcitriol (n = 25) subcutaneously within the first 6 h after calving. Blood was
sampled before treatment and 12 h later, then daily until 15 d in milk (DIM), and
analyzed for concentrations of ionized Ca (iCa), total Ca (tCa), total Mg (tMg),
and total P (tP), metabolites, and hormones. Urine was sampled in the first 7 DIM
and analyzed for concentrations of tCa, tMg, and creatinine. Neutrophil function
was evaluated in the first week postpartum. Dry matter intake and production
performance were evaluated for the first 36 DIM. Calcitriol administration
increased concentrations of calcitriol in plasma within 12 h of application from
51 to 427 pg/mL, which returned to baseline within 5 d. Concentrations of iCa and
tCa increased 24 h after treatment with calcitriol. Concentrations of iCa
(control = 1.08 vs. calcitriol = 1.20 mM), tCa (control = 2.23 vs. calcitriol =
2.33 mM), and tP (control = 1.47 vs. calcitriol = 1.81 mM) remained elevated in
cows treated with calcitriol until 3, 5, and 7 DIM, respectively, whereas
concentration of tMg (control = 0.76 vs. calcitriol = 0.67 mM) was less in
calcitriol cows than control cows until 3 DIM. Concentrations of parathyroid
hormone decreased in calcitriol cows compared with control cows (control = 441
vs. calcitriol = 336 pg/mL). Calcitriol tended to increase plasma concentrations
of beta-hydroxybutyrate and serotonin, but concentrations of glucose,
nonesterified fatty acids, and C-telopeptide of type I collagen in plasma did not
differ between treatments. Cows treated with calcitriol excreted more urinary tCa
(control = 0.5 vs. calcitriol = 2.1 g/d) and tMg (control = 4.5 vs. calcitriol =
5.0 g/d) in the first 7 and 2 DIM, respectively, than control cows. Compared with
control, calcitriol improved the proportion of neutrophils with oxidative burst
(control = 31.9 vs. calcitriol = 40.6%), mean fluorescence intensity for
oxidative burst (control = 90,900 vs. calcitriol = 99,746), and mean fluorescence
intensity for phagocytosis (control = 23,887 vs. calcitriol = 28,080). Dry matter
intake, yields of milk, and milk components did not differ between treatments.
Administration of 300 MUg of calcitriol at calving was safe and effective in
increasing blood concentration of iCa and plasma concentrations of calcitriol,
tCa, and tP for the first 6 d after treatment, and improved measures of innate
immune function in early-lactation Holstein cows.
PMID- 28501405
TI - Short communication: Nutrient consumption patterns of Lactobacillus acidophilus
KLDS 1.0738 in controlled pH batch fermentations.
AB - This work focused on elucidating the nutrient consumption patterns of
Lactobacillus acidophilus to guide the design of media for high-cell-density
culture. We investigated the nutrient consumption patterns of L. acidophilus KLDS
1.0738 in chemically defined media in controlled pH batch fermentations. The most
abundantly consumed amino acids, vitamins, ions, and purines and pyrimidines were
Glu and Gly, pyridoxine and nicotinamide, K+ and PO43-, and guanine and uracil,
respectively. The highest consumption rates for amino acids, vitamins, ions, and
purines and pyrimidines were Asp and Arg, folic acid and pyridoxine, Fe2+ and
Mn2+, and uracil and thymine, respectively. Furthermore, most of the amino acids,
as well as guanine, thymine, pyridoxine, folic acid, nicotinamide, Mg2+, PO43-,
and K+ had the highest bioavailability from the end of the lag growth phase to
the mid-exponential growth phase. The overall consumption of glucose, adenine
nucleotides, 2'-deoxyguanosine monohydrate, calcium pantothenate, Fe2+ and Mn2+
decreased with increasing average growth rate, indicating more effective use of
these nutritional components at a higher average growth rate, as biomass yield
based on nutritional component consumption increased. Our findings help to
formulate complex media for high-cell-density cultivation and provide a
theoretical basis for L. acidophilus feeding strategies.
PMID- 28501406
TI - Effect of inhibiting the lactogenic signal at calving on milk production and
metabolic and immune perturbations in dairy cows.
AB - During the periparturient period, the abrupt increase in energy demand for milk
production often induces metabolic and immunological disturbances in dairy cows.
Our previous work has shown that reducing milk output by milking once a day or
incompletely in the first few days of lactation reduces these disturbances. The
aim of this study was to reduce metabolic and immunological disturbances by
limiting milk production during the first week of lactation by inhibiting the
lactogenic signal driven by prolactin. Twenty-two fresh cows received 8 i.m.
injections of the prolactin-release inhibitor quinagolide (QUIN; 2 mg) or water
as a control (CTL). The first injection was given just after calving, and the
subsequent 7 injections were given every 12 h. Milk production was measured until
d 28 after calving. Blood samples were taken from d 1 (calving) to d 5 and then
on d 7, 10, 14, 21, and 28 to measure concentrations of urea, phosphorus,
calcium, glucose, nonesterified fatty acids (NEFA), beta-hydroxybutyrate, and
prolactin. Other blood samples were taken on d 2, 5, 10, and 28 to analyze
oxidative burst, phagocytosis, and the effect of the serum on the
lymphoproliferation of peripheral blood mononuclear cells from donor cows. Blood
prolactin concentration was lower from d 2 to 5 but higher from d 10 to 28 in the
QUIN cows than in the CTL cows. Milk production was lower from d 2 to 6 in the
QUIN cows than in the CTL cows (24.3 +/- 6.4 and 34.8 +/- 4.1 kg/d on average,
respectively). We observed no residual effect of quinagolide on milk production
after d 6. During the first week of lactation, blood glucose and calcium
concentrations were higher and beta-hydroxybutyrate concentration was lower in
the QUIN cows than in the CTL cows. Blood NEFA, urea, and phosphorus
concentrations were not affected by the treatment. At d 2 and 5, the phagocytosis
ability of polymorphonuclear leukocytes was not affected by treatment; however,
quinagolide injection enhanced the proportion of cells that entered oxidative
burst, The mitogen-induced proliferation of peripheral blood mononuclear cells
was greater when they were incubated with serum harvested from the CTL cows and
was negatively correlated with the NEFA concentration in the serum. Reducing the
prolactin peak at calving was effective in reducing milk production during the
first week of lactation without compromising the dairy cow's overall
productivity. Slowing the increase in milk production allowed a more gradual
transition from pregnancy to lactation and led to a reduction in metabolic stress
and an improvement in some immune system aspects during this period.
PMID- 28501407
TI - Amino acid composition of rumen bacteria and protozoa in cattle.
AB - Because microbial crude protein (MCP) constitutes more than 50% of the protein
digested in cattle, its AA composition is needed to adequately estimate AA
supply. Our objective was to update the AA contributions of the rumen microbial
AA flowing to the duodenum using only studies from cattle, differentiating
between fluid-associated bacteria (FAB), particle-associated bacteria (PAB), and
protozoa, based on published literature (53, 16, and 18 treatment means were used
for each type of microorganism, respectively). In addition, Cys and Met reported
concentrations were retained only when an adequate protection of the sulfur
groups was performed before the acid hydrolysis. The total AA (or true protein)
fraction represented 82.4% of CP in bacteria. For 10 AA, including 4 essential
AA, the AA composition differed between protozoa and bacteria. The most
noticeable differences were a 45% lower Lys concentration and 40% higher Ala
concentration in bacteria than in protozoa. Differences between FAB and PAB were
less pronounced than differences between bacteria and protozoa. Assuming 33% FAB,
50% PAB, and 17% of protozoa in MCP duodenal flow, the updated concentrations of
AA would decrease supply estimates of Met, Thr, and Val originating from MCP and
increase those of Lys and Phe by 5 to 10% compared with those calculated using
the FAB composition reported previously. Therefore, inclusion of the contribution
of PAB and protozoa to the duodenal MCP flow is needed to adequately estimate AA
supply from microbial origin when a factorial method is used to estimate duodenal
AA flow. Furthermore, acknowledging the fact that hydrolysis of 1 kg of true
microbial protein yields 1.16 kg of free AA substantially increases the estimates
of AA supply from MCP.
PMID- 28501408
TI - Understanding the gut microbiome of dairy calves: Opportunities to improve early
life gut health.
AB - Early gut microbiota plays a vital role in the long-term health of the host.
However, understanding of these microbiota is very limited in livestock species,
especially in dairy calves. Neonatal calves are highly susceptible to enteric
infections, one of the major causes of calf death, so approaches to improving gut
health and overall calf health are needed. An increasing number of studies are
exploring the microbial composition of the gut, the mucosal immune system, and
early dietary interventions to improve the health of dairy calves, revealing
possibilities for effectively reducing the susceptibility of calves to enteric
infections while promoting growth. Still, comprehensive understanding of the
effect of dietary interventions on gut microbiota-one of the key aspects of gut
health-is lacking. Such knowledge may provide in-depth understanding of the
mechanisms behind functional changes in response to dietary interventions.
Understanding of host-microbial interactions with dietary interventions and the
role of the gut microbiota during pathogenesis at the site of infection in early
life is vital for designing effective tools and techniques to improve calf gut
health.
PMID- 28501409
TI - Effect of different fat supplements on performance of dairy calves during cold
season.
AB - The objective of this experiment was to evaluate the effects of starter
supplementation with fat sources differing in their fatty acid (FA) profile on
performance of dairy calves during cold season. Sixty Holstein calves (3 d of
age; 39.7 +/- 3.8 kg of body weight) were randomly assigned to 1 of 5 starter
diets supplemented with (1) no fat or oil source (control), (2) 3% palm fat
(PLF), (3) 3% soybean oil (SBO), (4) 3% tallow (TAL), and (5) a 3.2% mixture
(MIX) of PLF, SBO, and fish oil. The fat supplements were substituted for corn in
the basal starter diet. Both the control and fat-supplemented diets contained
similar amounts of dietary crude protein (19.4%), but the latter had a slightly
higher quantity of calculated metabolizable energy (3.17 vs. 3.07 Mcal/kg) than
did the former. Calves were reared outdoor in individual pens during the cold of
winter with a mean ambient temperature of 5.0 degrees C during the study period.
Whole milk was offered twice daily from d 3 to 45 and once from d 46 to 49. The
animals were weaned on d 50 and monitored in their individual pens until d 70.
Supplementation with SBO and MIX increased both the dietary concentration and
ratio of essential FA (n-6 and n-3), whereas supplementation with TAL and PLF
made no change in the essential FA profile. Starter intake and average daily gain
were not affected by PLF and TAL supplements, but were reduced as a result of
feeding MIX. Feeding supplemental SBO did not affect starter intake, but tended
to improve average daily gain and final body weight. Fat sources had no effects
on body skeletal measurements, fecal score, digestibility, ruminal pH, ammonia,
and total volatile FA concentrations; however, feeding MIX increased rumen molar
proportion of propionate. No differences were observed in blood metabolites
across the treatments during the preweaning period. Plasma concentrations of
triacylglycerol and cholesterol increased when fat sources were supplemented and
glucose concentration increased when SBO was supplemented during the postweaning
period. Overall, addition of 3% PLF or TAL to the diet of young calves failed to
improve growth performance. Although addition of SBO and MIX increased the
dietary essential FA concentration, calf performance was only improved when SBO
was supplemented.
PMID- 28501410
TI - Effects of dietary energy allowance and decline in dry matter intake during the
dry period on responses to glucose and insulin in transition dairy cows.
AB - We assessed whether high energy intake during the early dry period [144% of
metabolizable energy (ME) requirements/d] followed by a gradual restriction of
energy intake in the close-up dry period (119% of ME/d; HEI) impaired whole-body
insulin sensitivity compared with a controlled energy intake (100% of ME/d; CEI)
throughout the 6-wk dry period. Multiparous Ayrshire dairy cows (n = 16) were
blocked by body weight, body condition score, and expected date of parturition
and were used in a randomized complete block design until 10 d after parturition.
Cows were fed either HEI or CEI diets based on grass silage during the first 3 wk
of the dry period and grass silage supplemented with a commercial concentrate
(30% of ME intake) during the final 3 wk of gestation. After calving, all cows
were fed grass silage ad libitum and an increasing amount of commercial
concentrate (maximum 9 kg at d 10 postpartum). Intravenous glucose tolerance
tests (IVGTT) and intravenous insulin challenges were performed -10 +/- 5 d (n =
15) and +10 +/- 1 d (n = 14) relative to parturition. Following glucose
injection, we did not find any treatment effects on glucose and insulin
responses. The prepartal nonesterified fatty acid (NEFA) response of the HEI
group was blunted, basal NEFA and the decrement of NEFA were smaller, and the
area under the response curve (AUC) of NEFA was less negative in HEI cows than in
CEI cows. The NEFA response reversed after parturition; the NEFA AUC of the HEI
group was more negative than that of the CEI group. We did not find similar
responses after insulin injection. Across the treatments, NEFA AUC correlated
strongly with the basal NEFA concentration during the IVGTT pre- and postpartum.
Calculated and model-based indices characterizing the overall glucose tolerance
and beta-cell function and the insulin sensitivity were higher after parturition
than during the dry period. Consistent with the lower basal insulin, the acute
insulin release after the glucose infusion was smaller in postpartal IVGTT than
in prepartal IVGTT. The results suggest that whole-body insulin sensitivity of
the cows increased after parturition. However, the role of peripheral insulin
sensitivity in the regulation of glucose partitioning seems to be minor relative
to the major change in insulin secretion and clearance during the periparturient
period.
PMID- 28501412
TI - Sudden Death in a Diver: A Diagnostic Conundrum.
AB - We discuss the case of an experienced diver who ran out of air during his final
ascent while scuba diving. He lost consciousness rapidly after surfacing and
despite immediate cardiopulmonary resuscitation, could not be revived. On arrival
at the emergency department he was noted to have copious amounts of blood in his
upper airway and had developed extensive subcutaneous emphysema. Large amounts of
air were observed in the central circulation following a postmortem computerized
tomography scan as well as pneumomediastinum, a small right-sided hemothorax, and
extensive subcutaneous emphysema. We discuss several potential pathophysiological
mechanisms that might explain these findings. Finally, we end with a
recommendation for an expedient whole-body postmortem computerized tomography
scan and autopsy by a suitably qualified pathologist in the investigation of all
dive-related fatalities, where possible.
PMID- 28501411
TI - Short communication: Associations between blood glucose concentration, onset of
hyperketonemia, and milk production in early lactation dairy cows.
AB - The objectives of this study were to describe the associations between
hypoglycemia and the onset of hyperketonemia (HYK) within the first 6 wk of
lactation, to evaluate the effects of body condition score at calving on glucose
concentration, and to study the effects of hypoglycemia on milk production. A
total of 621 dairy cows from 6 commercial dairy farms in Germany were enrolled
between 1 and 4 d in milk (DIM). Cows were tested twice weekly using an
electronic handheld meter for glucose and beta-hydroxybutyrate (BHB),
respectively, for a period of 42 d. Hypoglycemia was defined as glucose
concentration <=2.2 mmol/L. Hyperketonemia was defined as a BHB concentration
>=1.2 mmol/L. The onset of HYK was described as early onset (first HYK event
within the first 2 wk postpartum) and late onset (first HYK event in wk 3 to 6
postpartum). The effect of ketosis status on blood glucose within 42 DIM was
evaluated using a generalized linear mixed model. No effect was observed of HYK
on glucose concentration in primiparous cows. Multiparous cows with early-onset
HYK had a lower glucose concentration (-0.21 mmol/L) compared with nonketotic
cows. Overall, primiparous cows had a lower prevalence and incidence of
hypoglycemia than multiparous cows. Hypoglycemia in multiparous cows was
associated with higher first test-day milk production and 100 DIM milk
production. In conclusion, hypoglycemia mainly occurred in multiparous cows with
early-onset HYK, whereas primiparous cows were at a lower risk for hypoglycemia.
PMID- 28501413
TI - Managing Traumatic Brain Injury: Translating Military Guidelines to the
Wilderness.
AB - Traumatic brain injury (TBI) is a common injury on the battlefield. Much of what
medics do to manage these injuries on the battlefield can be translated to other
austere environments, such as wilderness or disaster settings. The recognition
and diagnosis of TBI can be difficult even in the hospital, but basic
understanding of how to define a TBI and prevent secondary injuries can be
accomplished with relatively few resources and little training. This article
outlines what a TBI is and how to manage it in the field.
PMID- 28501414
TI - Editorial commentary: Genetic contributions to cardiovascular disease: The
blurred lines between monogenic and polygenic traits.
PMID- 28501415
TI - Reduced electrode arrays for the automated detection of rhythmic and periodic
patterns in the intensive care unit: Frequently tried, frequently failed?
AB - OBJECTIVE: To investigate the effect of systematic electrode reduction from a
common 10-20 EEG system on pattern detection sensitivity (SEN). METHODS: Two
reviewers rated 17130 one-minute segments of 83 prospectively recorded cEEGs
according to the ACNS standardized critical care EEG terminology (CCET),
including burst suppression patterns (BS) and unequivocal electrographic
seizures. Consensus annotations between reviewers were used as a gold standard to
determine pattern detection SEN and specificity (SPE) of a computational
algorithm (baseline, 19 electrodes). Electrodes were than reduced one by one in
four different variations. SENs and SPEs were calculated to determine the most
beneficial assembly with respect to the number and location of electrodes.
RESULTS: High automated baseline SENs (84.99-93.39%) and SPEs (90.05-95.6%) were
achieved for all patterns. Best overall results in detecting BS and CCET patterns
were found using the "hairline+vertex" montage. While the "forehead+behind ear"
montage showed an advantage in detecting ictal patterns, reaching a 15% drop of
SEN with 10 electrodes, all montages could detect BS sufficiently if at least
nine electrodes were available. CONCLUSION: For the first time an automated
approach was used to systematically evaluate the effect of electrode reduction on
pattern detection SEN in cEEG. SIGNIFICANCE: Prediction of the expected detection
SEN of specific EEG patterns with reduced EEG montages in ICU patients.
PMID- 28501416
TI - Digoxin and 30-Day All-Cause Readmission in Long-Term Care Residents Hospitalized
for Heart Failure.
AB - BACKGROUND: Digoxin use has been shown to be associated with a lower risk of 30
day all-cause hospital readmissions in older patients with heart failure (HF). In
the current study, we examined this association among long-term care (LTC)
residents hospitalized for HF. METHODS: Of the 8049 Medicare beneficiaries
discharged alive after hospitalization for HF from 106 Alabama hospitals, 545
(7%) were LTC residents, of which 227 (42%) received discharge prescriptions for
digoxin. Propensity scores for digoxin use, estimated for each of the 545
patients, were used to assemble a matched cohort of 158 pairs of patients
receiving and not receiving digoxin who were balanced on 29 baseline
characteristics. Hazard ratios (HRs) and 95% confidence intervals (CIs) for
outcomes associated with digoxin among matched patients were estimated using Cox
regression models. RESULTS: Matched patients (n = 316) had a mean age of 83
years, 74% were women, and 18% African American. Thirty-day all-cause readmission
occurred in 21% and 20% of patients receiving and not receiving digoxin,
respectively (HR, 1.02; 95% CI, 0.63-1.66). Digoxin had no association with all
cause mortality (HR, 0.90; 95% CI, 0.48-1.70), HF readmission (HR, 0.90; 95% CI,
0.38-2.12), or a combined endpoint of all-cause readmission or all-cause
mortality (HR, 0.97; 95% CI, 0.65-1.45) at 30 days. These associations remained
unchanged at 1 year postdischarge. CONCLUSIONS: The lack of an association
between digoxin and 30-day all-cause readmission in older nursing home residents
hospitalized for HF is intriguing and needs to be interpreted with caution given
the small sample size.
PMID- 28501417
TI - Prevalence of Frailty Assessed by Fried and Kihon Checklist Indexes in a
Prospective Cohort Study: Design and Demographics of the Kyoto-Kameoka
Longitudinal Study.
AB - OBJECTIVE: The Kyoto-Kameoka Study was launched in 2011-2012 to identify the
associations among food intake, nutritional status, physical activity, oral
function, quality of life or social capital, the use of long-term care insurance
(LTCI) system, and healthy lifespan in community-dwelling older people as a part
of the World Health Organization Safe Community program. DESIGN: A prospective
cohort study, reporting baseline demographics (cross-sectional data). SETTING AND
PARTICIPANTS: We conducted 2 mailed self-administered questionnaire surveys; one
is a complete population survey with a comprehensive survey of needs in the
sphere of daily life (NSDL) that included 2 different frailty indexes, the Kihon
Checklist (KCL) and the Fried phenotype, socioeconomic status, general and
psychological health, and social relationships; followed by the more detailed
Health and Nutrition Survey. A slightly modified NSDL survey was conducted again
in 2013. Survival time, LTCI certification, and medical and long-term care costs
after the baseline survey will be followed. RESULTS: Of 18,231 NSDL
questionnaires distributed, 13,294 people responded (response rate: 72.92%; mean
age 73.7 +/- 6.4 and 75.1 +/- 7.2 years for men and women, respectively; 12,054
people without and 1240 with LTCI certification). In people without LTCI, the
proportion of robust, prefrail, and frail were 30.3%, 59.8%, and 9.9% in men and
25.3%, 64.7%, and 10.0% in women, according to the Fried index. The proportion of
frail people as defined by KCL >=7 was 30.8% in men and 33.3% in women.
CONCLUSIONS: The study is the first to document frailty prevalence using both
Fried and KCL measures with a complete city population survey among older
Japanese in the community as a part of World Health Organization Safe Community
program. The study is expected to provide valuable evidence of the effects of
lifestyle habits on long-term care prevention and healthy life span.
PMID- 28501418
TI - Comparability and feasibility of wrist- and hip-worn accelerometers in free
living adolescents.
AB - OBJECTIVE: To determine the comparability and feasibility of wrist- and hip-worn
accelerometers among free-living adolescents. DESIGN: 89 adolescents (age=13
14years old) from eight secondary schools in New South Wales (NSW), Australia
wore wrist-worn GENEActiv and hip-worn ActiGraph (GT3X+) accelerometers
simultaneously for seven days and completed an accelerometry behavior
questionnaire. METHODS: Bivariate correlations between the wrist- and hip-worn
out-put were used to determine concurrent validity. Paired samples t-test were
used to compare minutes per day in moderate-to-vigorous physical activity (MVPA).
Group means and paired sample t-tests were used to analyze participants'
perceptions of the wrist- and hip-worn monitoring protocols to assist with
determining the feasibility. RESULTS: Wrist-worn accelerometry compared favorably
with the hip-worn in average activity (r=0.88, p<0.001) and MVPA (r=0.84 p<0.001,
mean difference=3.54min/day, SD=12.37). The wrist-worn accelerometer had 50%
fewer non-valid days (75 days, 12%) than the hip-worn accelerometer (n=152,
24.4%). Participants reported they liked to wear the device on the wrist
(p<0.01), and that it was less uncomfortable (p=0.02) and less embarrassing to
wear on the wrist (p<0.01). Furthermore, that they would be more willing to wear
the device again on the wrist over the hip (p<0.01). CONCLUSIONS: Our findings
reveal there is a strong linear relationship between wrist- and hip-worn
accelerometer out-put among adolescents in free-living conditions. Adolescent
compliance was significantly higher with wrist placement, with participants
reporting that it was more comfortable and less embarrassing to wear on the
wrist.
PMID- 28501419
TI - Brachytherapy for Conservative Treatment of Invasive Penile Carcinoma: Prognostic
Factors and Long-Term Analysis of Outcome.
AB - PURPOSE: To report the largest experience with brachytherapy as a conservative
approach for the treatment of penile carcinoma. METHODS AND MATERIALS: We
examined the outcomes of 201 patients treated at our institution over 45 years
for invasive squamous cell carcinoma of the glans penis by brachytherapy.
RESULTS: With a median follow-up of 10.7 years, local relapse as first failure
was reported in 37 patients (18.9%), and 24 of 31 patients (77.4%) with local
failure only were in complete remission after new treatment. At last follow-up 25
patients (12.4%) underwent partial surgery and 7 (3.5%) total penectomies for
relapse. Fifty patients (24.8%) presented urethral stenosis requiring at least 1
dilatation, and 14 (7%) required limited surgeries for toxicities. At 5 years the
estimated overall survival rate was 79% (95% confidence interval 73%-85%). The
estimated original local control rate was 82% (95% confidence interval 76%-88%).
Presence of inguinal lymph node metastasis and tumor size correlated with a
poorer overall and disease-free survival in univariate and multivariate analyses.
In univariate analysis, neutrophilia at diagnosis correlated with a higher
probability of distant relapse (P=.025), and a dose >=62 Gy correlated with
better local control in N0 patients (P=.038). The risk of complication correlated
with the dose, treated volume, and dose rate. CONCLUSION: This large
institutional experience confirms the high local control achieved with
brachytherapy for penile carcinoma, with the advantage of organ preservation.
Most local relapses are efficiently salvaged by second-intent surgery.
PMID- 28501420
TI - Manipulation of visual information affects control strategy during a visuomotor
tracking task.
AB - Proper understanding of motor control requires insight into the extent and manner
in which task performance and control strategy are influenced by various aspects
of visual information. We therefore systematically manipulated the visual
presentation (i.e., scaling factor and optical flow density) of a visuomotor
tracking task without changing the task itself, and investigated the effect on
performance, effort, motor control strategy (i.e., anticipatory or corrective
steering) and underlying neuromechanical parameters (i.e., intrinsic muscle
stiffness and damping, and proprioceptive and visual feedback). Twenty healthy
participants controlled the left-right position of a virtual car (by means of
wrist rotations in a haptic robot) to track a slightly curved virtual road
(presented on a 60" LED screen), while small torque perturbations were applied to
the wrist (1.25-20Hz multisine) for quantification of the neuromechanical
parameters. This visuomotor tracking task was performed in conditions with
low/medium/high scaling factor and low/high optical flow density. Task
performance was high in all conditions (tracking accuracy 96.6%-100%); a higher
scaling factor was associated with slightly better performance. As expected,
participants did adapt their control strategy and the use of proprioceptive and
visual feedback in response to changes in the visual presentation. These findings
indicate that effects of visual representation on motor behavior should be taken
into consideration in designing, interpreting and comparing experiments on motor
control in health and disease. In future studies, these insights might be
exploited to assess the sensory-motor adaptability in various clinical
conditions.
PMID- 28501421
TI - "What time is my next meal?" delay-discounting individuals choose smaller
portions under conditions of uncertainty.
AB - 'Dietary' delay discounting is typically framed as a trade-off between immediate
rewards and long-term health concerns. Our contention is that prospective
thinking also occurs over shorter periods, and is engaged to select portion sizes
based on the interval between meals (inter-meal interval; IMI). We sought to
assess the extent to which the length of an IMI influences portion-size
selection. We predicted that delay discounters would show 'IMI insensitivity'
(relative lack of concern about hunger or fullness between meals). In particular,
we were interested in participants' sensitivity to an uncertain IMI. We
hypothesized that when meal times were uncertain, delay discounters would be less
responsive and select smaller portion sizes. Participants (N = 90) selected
portion sizes for lunch. In different trials, they were told to expect dinner at
5pm, 9pm, and either 5pm or 9pm (uncertain IMI). Individual differences in future
orientation were measured using a monetary delay-discounting task. Participants
chose larger portions when the IMI was longer (p < 0.001). When the IMI was
uncertain, delay-discounting participants chose smaller portions than the average
portion chosen in the certain IMIs (p < 0.05). Furthermore, monetary discounting
mediated a relationship between BMI and smaller portion selection in uncertainty
(p < 0.05). This is the first study to report an association between delay
discounting and IMI insensitivity. We reason that delay discounters selected
smaller portions because they were less sensitive to the uncertain IMI, and
overlooked concerns about potential future hunger. These findings are important
because they illustrate that differences in discounting are expressed in short
term portion-size decisions and suggest that IMI insensitivity increases when
meal timings are uncertain. Further research is needed to confirm whether these
findings generalise to other populations.
PMID- 28501422
TI - Desideratum for GUT: A functional semantics for sport.
PMID- 28501423
TI - Teratoma of the nervous system: A case series.
AB - Teratoma is a common form of germ cell tumors composed of multiple tissues
foreign to the site in which arise with a histological representation of all
three germ cell layers. Intracranial teratomas are very rare. In this study, we
report three cases of intracranial teratomas with an interesting clinical course,
neuroradiology, and outcome. In addition, we review the literature and convey
important messages to the neuroscience community regarding issues related to the
management of these rare tumors. The present cases are interesting examples of
intracranial teratoma in terms of location of the tumor and neuroimaging
findings. Delay in surgical intervention may complicate the course of the disease
with progressive enlargement of tumors and development of complication including
hydrocephalus. Using endoscopic surgical techniques may emerge as the preferred
intervention option as compared to other traditional methods. We recommend the
establishment of a national and international registry for intracranial tumors.
PMID- 28501424
TI - RO0504985 is an inhibitor of CMGC kinase proteins and has anti-human
cytomegalovirus activity.
AB - Public-private partnerships allow many previously unavailable compounds to be
screened for antiviral activity. Here a screening method was used to identify an
oxindole compound, RO0504985, from a Roche kinase inhibitor library that
inhibited human cytomegalovirus (HCMV) protein production. RO0504985 was
previously described as an inhibitor of cyclin-dependent kinase 2 (CDK2).
However, using kinase selectivity assays it was found that RO0504985 was an
inhibitor of several CMGC group kinase proteins, including CDK2. Using virus
yield reduction assays it was observed that RO0504985 inhibited replication of
different HCMV strains at low micromolar concentrations. Western blotting was
used to investigate how RO0504985 inhibited HCMV replication. Treatment of HCMV
infected cells with RO0504985 inhibited production of the immediate early viral
IE2 proteins and the late viral protein pp28. Thus, RO0504985 inhibited HCMV
replication by preventing production of specific HCMV proteins necessary for
virus replication.
PMID- 28501425
TI - The effects of kratom on restraint-stress-induced analgesia and its mechanisms of
action.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa and its extracts are called
kratom (dried leaves, extract). They contain several alkaloids with an affinity
for different opioid receptors. They are used in traditional medicine for the
treatment of different diseases, as a substitute by opiate addicts, and to
mitigate opioid withdrawal symptoms. Apart from their medical properties, they
are used to enhance physical endurance and as a means of overcoming stress.
PURPOSE: The aim of this study was to determine the mechanisms underlying the
effects of kratom on restraint-stress-induced analgesia which occurs during or
following exposure to a stressful or fearful stimulus. METHODS: To gain further
insights into the action of kratom on stress, we conducted experiments using
restraint stress as a test system and stress-induced analgesia as a test
parameter. Using transgenic mu opioid-receptor (MOR) deficient mice, we studied
the involvement of this receptor type. We used nor-binaltorphimine (BNT), an
antagonist at kappa opioid receptors (KOR), to study functions of this type of
receptor. Membrane potential assay was also employed to measure the intrinsic
activity of kratom in comparison to U50,488, a highly selective kappa agonist.
RESULTS: Treatment with kratom diminished stress-induced analgesia in wildtype
and MOR knockout animals. Pretreatment of MOR deficient mice with BNT resulted in
similar effects. In comparison to U50,488, kratom exhibited negligible intrinsic
activity at KOR alone. CONCLUSIONS: The results suggest that the use of kratom as
a pharmacological tool to mitigate withdrawal symptoms is related to its action
on KOR.
PMID- 28501426
TI - Attenuation of diabetic nephropathy by Sanziguben Granule inhibiting EMT through
Nrf2-mediated anti-oxidative effects in streptozotocin (STZ)-induced diabetic
rats.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic nephropathy (DN) is an acute and serious
diabetic complication characterized by renal hypertrophy and renal fibrosis with
the expansion of extracellular matrices. Diabetic nephropathy has become a major
cause of end-stage kidney disease. Sanziguben Granule (SZGB) is a compound
prescription which has been widely applied in clinical medicine for the
prevention and treatment of diabetic nephropathy as well as for acute and chronic
kidney injuries. However, the mechanism of protective effects of SZGB in DN
remains unclear. MATERIALS AND METHODS: In this research, we investigated the
effects of SZGB on renal interstitial fibrosis, antioxidant proficiency, and
apoptosis in streptozotocin (STZ)-induced diabetic rats. Diabetic rats were
prepared by performing a right uninephrectomy along with a single intraperitoneal
injection of STZ. Rats were divided into six groups including sham, DN, SZGB-D,
SZGB-Z, SZGB-G and fosinopril. SZGB and fosinopril were given to rats by gavage
for 12 weeks. Samples from urine, blood and kidneys were collected for
biochemical, histological, immunohistochemical and western blot analyses.
RESULTS: We found that rats treated with SZGB showed reduced 24-h urinary protein
excretion along with reduced serum total cholesterol (TC) and triglyceride (TG)
levels. SZGB was also shown to prevent the disruption of catalase activity and
reduce serum urea, creatinine, and renal malondialdehyde while increasing
glutathione levels. Moreover, SZGB administration markedly improved the
expression levels of E-cadherin, 4-HNE, Nrf2, HO-1, and Bcl-2, while it decreased
the expression levels of Vimentin, alpha-SMA and Cleaved caspase-3 in the kidneys
of diabetic rats. The renoprotective effects of SZGB was believed to be mediated
by its antioxidant capacity, and SZGB treatment attenuated renal fibrosis through
stimulating the nuclear factor erythroid-2-related factor 2 (Nrf2) signaling
pathway in the diabetic kidneys. CONCLUSIONS: Therefore, it is suggested that
SZGB can restrain epithelial-mesenchymal transition (EMT) through stimulating the
Nrf2 pathway, which improves renal interstitial fibrosis in DN.
PMID- 28501427
TI - Ethnopharmacological approach to the herbal medicines of the "Elements Alpha to
Delta" in Nikolaos Myrepsos' Dynameron. Part II.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Dynameron is a Byzantine medical compendium,
divided into 24 sections, the "Elements", containing 2667 recipes, most of which
inherited by previous physicians of the classic ancient Greek and Hellenistic,
and imperial Roman periods. AIM OF THE STUDY: In continuation to our previous
study concerning the first and largest chapter of the "Element Alpha" of Nikolaos
Myrepsos' Dynameron (Valiakos et al., 2015), this paper focuses on the plants
quoted in the recipes of the eight following chapters entitled "About Salts",
"About Honeypacks" and "About Spreads", all belonging to the same "Element
Alpha"; "About Antitussives" and "About Suppositories" belonging to the "Element
Beta"; "About women's Cathartics" belonging to the "Element Gamma"; "About
Drossaton" and "About Diachrisma", both belonging to the "Element Delta".
MATERIALS AND METHODS: Our main primary source material was the codex kept in the
National Library of France (in Paris) under the number grec. 2243, which is the
older and larger codex of Dynameron (Valiakos et al., 2015). RESULTS: The present
study led us to the interpretation of 277 plants under different names, among
which we recognized 57 medicinal plants listed by the European Medicines Agency,
one of them with negative monograph (i.e. Chelidonium majus). In addition, there
are identified taxa related to those quoted by EMA as herbal medicines. The
plants appearing in the examined Elements belong to various families of which the
most frequent are: Apiaceae 10.11%; Lamiaceae 7.22%; Asteraceae 6.86%; Rosaceae
6.5% and Fabaceae 6.14%. CONCLUSIONS: A total of 277 species have been
catalogued, most of which are referred in our previous publication (Valiakos et
al., 2015). Among them, 56 plants still play a very important role in medical
practice, as they are used as traditional herbal medicines (www.ema.eu). This
evidence is a proof that the use of medicinal plants remains valuable from the
ancient times until today. The recipes, in contrast to older medical compendia,
contain precise measurements of ingredients and dosages for every drug, which
seem to reflect empirical logic.
PMID- 28501428
TI - Management of ovarian stimulation for IVF: narrative review of evidence provided
for World Health Organization guidance.
AB - In this paper, a review of evidence provided to the World Health Organization
(WHO) guideline development, who prepare global guidance on the management of
ovarian stimulation for women undergoing IVF, is presented. The purpose of
ovarian stimulation is to facilitate retrieval of multiple oocytes during a
single IVF cycle. Availability of multiple oocytes compensates for inefficiencies
in subsequent stages of the cycle, which include oocyte maturation, IVF, embryo
culture, embryo transfer, and implantation. Multiple embryos can be transferred
in most women, and spare embryos can be frozen to allow for future chances of
pregnancy without the need for repeated ovarian stimulation and oocyte retrieval.
Our evidence synthesis team addressed 10 clinical questions on management of
ovarian stimulation for IVF, prepared a narrative review of the evidence and
drafted recommendations to be considered through WHO guideline development
processes. Our main outcome measures were live birth, clinical pregnancy, and
ovarian hyperstimulation syndrome.
PMID- 28501430
TI - Kinetic properties and affinities for sulfonamide inhibitors of an alpha-carbonic
anhydrase (CruCA4) involved in coral biomineralization in the Mediterranean red
coral Corallium rubrum.
AB - We report the kinetic properties and sulfonamide inhibition profile of an alpha
carbonic anhydrase (CA, EC 4.2.1.1), named CruCA4, identified in the red coral
Corallium rubrum. This isoform is involved in the biomineralization process
leading to the formation of a calcium carbonate skeleton. Experiments performed
on the recombinant protein show that the enzyme has a "moderate activity" level.
Our results are discussed compared to values obtained for other CA isoforms
involved in biomineralization. This is the first study describing the biochemical
characterization of an octocoral CA.
PMID- 28501429
TI - Permanent prostate brachytherapy postimplant magnetic resonance imaging dosimetry
using positive contrast magnetic resonance imaging markers.
AB - PURPOSE: Permanent prostate brachytherapy dosimetry using computed tomography
magnetic resonance imaging (CT-MRI) fusion combines the anatomic detail of MRI
with seed localization on CT but requires multimodality imaging acquisition and
fusion. The purpose of this study was to compare the utility of MRI only
postimplant dosimetry to standard CT-MRI fusion-based dosimetry. METHODS AND
MATERIALS: Twenty-three patients undergoing permanent prostate brachytherapy with
use of positive contrast MRI markers were included in this study. Dose
calculation to the whole prostate, apex, mid-gland, and base was performed via
standard CT-MRI fusion and MRI only dosimetry with prostate delineated on the
same T2 MRI sequence. The 3-dimensional (3D) distances between seed positions of
these two methods were also evaluated. Wilcoxon-matched-pair signed-rank test
compared the D90 and V100 of the prostate and its sectors between methods.
RESULTS: The day 0 D90 and V100 for the prostate were 98% versus 94% and 88%
versus 86% for CT-MRI fusion and MRI only dosimetry. There were no differences in
the D90 or V100 of the whole prostate, mid-gland, or base between dosimetric
methods (p > 0.19), but prostate apex D90 was high by 13% with MRI dosimetry (p =
0.034). The average distance between seeds on CT-MRI fusion and MRI alone was 5.5
mm. After additional automated rigid registration of 3D seed positions, the
average distance between seeds was 0.3 mm, and the previously observed
differences in apex dose between methods was eliminated (p > 0.11). CONCLUSIONS:
Permanent prostate brachytherapy dosimetry based only on MRI using positive
contrast MRI markers is feasible, accurate, and reduces the uncertainties arising
from CT-MRI fusion abating the need for postimplant multimodality imaging.
PMID- 28501431
TI - Lipase-catalyzed kinetic resolution as key step in the synthesis of
enantiomerically pure sigma ligands with 2-benzopyran structure.
AB - In order to obtain enantiomerically pure sigma1 receptor ligands with a 2
benzopyran scaffold an Oxa-Pictet-Spengler reaction with the enantiomerically
pure 2-phenylethanol derivatives (R)-4 and (S)-4 was envisaged. The kinetic
resolution of racemic alcohol (+/-)-4 using Amano Lipase PS-C II and isopropenyl
acetate in tert-butyl methyl ether led to the (R)-configured alcohol (R)-4 in 42%
yield with an enantiomeric excess of 99.6%. The (S)-configured alcohol (S)-4 was
obtained by Amano Lipase PS-C II catalyzed hydrolysis of enantiomerically
enriched acetate (S)-5 (76.9% ee) and provided (S)-4 in 26% yield and 99.7% ee.
The absolute configuration of alcohol (R)-4 was determined by exciton coupled CD
spectroscopy of the bis(bromobenzoate) (R)-7. The next important step for the
synthesis of 2-benzopyrans 2 and 3 was the Oxa-Pictet-Spengler reaction of the
enantiomerically pure alcohols (R)-4 and (S)-4 with piperidone ketal 8 and
chloropropionaldehyde acetal 12. The conformationally restricted spirocyclic 2
benzopyrans 2 revealed higher sigma1 affinity than the more flexible aminoethyl
derivatives 3. The (R)- and (R,R)-configured enantiomers (R)-2 and (R,R)-3
represent the eutomers of this class of compounds with eudismic ratios of 4.8
(2b) and 4.5 (2c). High sigma1/sigma2 selectivity (>49) was found for the most
potent sigma1 ligands (R)-2b, (R)-2c, (R)-2d, and (S)-2d (Ki(sigma1) 9-15nM).
PMID- 28501432
TI - Diverse size approach to incorporate and extend highly fluorescent unnatural
nucleotides into DNA.
AB - We have prepared a series of size-diverse unnatural nucleotides containing
fluorescent (dApyrTP, dUpyrTP, dUantTP, dUthiTP) and quencher (dUazoTP) units, as
well as nucleotides presenting small functional groups (dAethTP, dAoctTP,
dUethTP, dUiodTP), all based on deoxyadenosine and deoxyuridine, and examined
their suitability for use in enzymatic incorporation and extension into DNA. We
observed a size-dependence of the incorporation and extension capability
(following the order dUiodTP=dUethTP=dUthiTP>dUazoTP>dUpyrTP>dUantTP) during
primer extension. This result was supported by circular dichroism (CD) spectra,
which revealed a trend in the different B-form DNA structures depending on the
size of the unit at the 5-position of the deoxyuridine
(dUiodTP>dUethTP>dUthiTP>dUpyrTP), obtained from the PCR products. Interestingly,
dUthiTP could be incorporated and extended into long DNA strands during primer
extension and even PCR amplification, with CD spectroscopy confirming a stable
secondary B-form duplex DNA structure. We observed full-length extension products
even when combining dUthiTP with a template containing 24 continuous dA units
during the primer extension. Thus, we believe that dUthiTP is a promising
fluorescent nucleotide for a diverse range of biological applications requiring
multiple incorporation and extension directly without disruption of B-form DNA
structures.
PMID- 28501433
TI - Responsiveness of the Self-Administered Foot Evaluation Questionnaire (SAFE-Q) in
patients with hallux valgus.
AB - BACKGROUND: In this study, we investigated the responsiveness of the Self
Administered Foot Evaluation Questionnaire (SAFE-Q) for patient's assessment
before and after hallux valgus surgery. METHODS: Patient-reported answers on the
SAFE-Q and Short Form-36 (SF-36) before and at a mean of 3-4 and 9-12 months
after hallux valgus surgery were analyzed. Data of 100 patients (92 women, eight
men) from 36 institutions throughout Japan were used for analysis. RESULTS: In
all subscales of the SAFE-Q, the trend of increased scores after surgery was
statistically significant (P < 0.001). Among the patients with available scores
both before and at 9-12 months after surgery (n = 66), the largest effect sizes
(ESs) were observed for shoe-related (1.60), pain and pain-related (1.05), and
general health and well-being (0.84) scales. In the SF-36 (n = 64), the largest
ES was observed for the bodily pain scale (0.86). Less notable changes were
observed for the remaining SF-36 domains. CONCLUSION: The SAFE-Q is the first
patient-reported outcome measure which includes a quality of life assessment of
shoes. In our cohort, the most remarkable responsiveness was observed for the
shoe-related subscale. Based on its responsiveness, the SAFE-Q appears to be
sufficient for evaluation of foot-related quality of life before and after
surgery.
PMID- 28501434
TI - Risk stratification for predicting symptomatic skeletal events (SSEs) in breast
cancer patients with bone metastases.
AB - BACKGROUND: Symptomatic skeletal events (SSEs) affect many patients with bone
metastases from breast cancer. However, predictive models of SSEs in patients
with bone metastases from breast cancer have not been established for clinical
use. The purpose of this study is to examine risk factors for SSEs in those
patients and by combining these risk factors patients are classified into several
groups. With this risk-stratification model, we can identify patients at higher
risk of SSEs and require close follow-up to maintain ADL. METHODS: Participants
included 189 female patients with bone metastases from breast cancer and treated
in our institute between 2009 and 2012. To assess risk factors for the first
SSEs, clinical data at the time of registration were assessed. To estimate the
effects of covariates, we used cause-specific hazard modeling. RESULTS:
Multivariate analysis revealed that a high number of metastasized vertebral
bodies (>=20) (p < 0.001) and elevated carcinoembryonic antigen (CEA) level (>5
ng/mL) (p = 0.003) were risk factors for SSEs. Patients were classified into four
subgroups according to the combination of the number of vertebral metastases and
CEA level: patients with CEA level > 5 ng/mL and >=20 vertebral metastases;
patients with CEA level <= 5 ng/mL and >=20 vertebral metastases; patients with
CEA level > 5 ng/mL and <20 vertebral metastases; and patients with CEA level <=
5 ng/mL and <20 vertebral metastases. Cumulative incidences of SSEs in these four
subgroups at 6 months were 35.6%, 15.6%, 9.3%, and 3.7%, respectively.
CONCLUSIONS: Patients with elevated CEA level (>5 ng/mL) and extensive vertebral
metastases (>=20) should be closely monitored in routine clinical care, to allow
prevention of pathological fracture or paraplegia with the intervention of
orthopedists or radiologists.
PMID- 28501435
TI - Risk factors for cognitive decline following osteoporotic vertebral fractures: A
multicenter cohort study.
AB - BACKGROUND: Osteoporotic vertebral fractures (OVFs) are the most common cause of
intractable back pain and reduced activities of daily living (ADL), which may
affect cognitive function. However, no previous studies have reported a change in
cognitive function after OVFs. The purpose was to reveal cognitive function
changes after OVFs and investigate the risk factors for cognitive decline.
METHODS: Consecutive patients with symptomatic OVFs were enrolled in a
prospective multicenter cohort study. The inclusion criteria were age >65 years,
diagnosis of acute or subacute OVF, and back pain onset within 2 months prior to
presentation. Cognitive function was assessed with the mini-mental state
examination. Medical history, radiological findings, and ADL were investigated as
risk factors for cognitive decline. RESULTS: We recruited a sample of 339
patients (58 men and 281 women) who met the inclusion criteria. Patients
underwent examinations and completed questionnaires at both the time of
enrollment and at 6-month follow-up. At 6-month follow-up, cognitive decline was
observed in 26 (7.7%) patients. Medical history, including comorbidities and
sports activities, did not affect odds ratios (ORs). However, elevated ORs were
associated with delayed union (OR: 4.67, 95% Confidence interval: 1.22-17.87). In
addition, significantly increased ORs were associated with reduced ADL at 6-month
follow-up. CONCLUSIONS: The current results revealed the incidence of cognitive
decline after the onset of OVF. Delayed union and reduced ADL at 6-month follow
up were associated with cognitive decline. Patients with cognitive decline
experienced significantly reduced quality of life. These results highlight the
importance of preventing cognitive impairment in patients with symptomatic OVF.
Physical treatment or early surgical treatment may provide appropriate options,
particularly for patients with suspected delayed union.
PMID- 28501436
TI - Identification of the bovine HSL gene expression profiles and its association
with fatty acid composition and fat deposition traits.
AB - Hormone-sensitive lipase (HSL) is an intracellular neutral lipase capable of
hydrolysing a variety of esters and is considered to be a candidate gene
affecting fat deposition traits. Gene expression profiles of HSL were analysed in
various adipose tissues of cattle, and the effect of HSL on lipid metabolism
genes was analysed by a PCR array. Novel polymorphisms were identified within the
HSL regulatory domain by sequencing, and the relationship between HSL variants
and fat deposition traits was analysed. HSL mRNA was highly expressed in the
subcutaneous and visceral fat of cattle. CPT1B/CPT1C and other lipocatabolic
genes were upregulated, and lipogenesis-related genes (FASN, LPL and ACOT12) were
downregulated by HSL overexpression in BFFs. Five novel variants in the HSL
functional domain were significantly associated with fat deposition traits,
including FCR, LBT, MFW and fatty acid composition. HSL plays a pivotal role in
the regulation of lipolysis and fatty acid biosynthesis in beef cattle.
PMID- 28501437
TI - Electronic noses: Powerful tools in meat quality assessment.
AB - Main factors that are considered by consumers when choosing meat products are
colour and aroma, of which the latter is a more reliable indicator of quality.
However, a simple sensory evaluation of hedonistic qualities is often not
sufficient to determine whether protein is past its shelf life, and consumption
of spoiled meat can lead to serious health hazards. Some volatile compounds can
be used as spoilage indicators, and so a device equipped with a sensor sensitive
to particular odorants would prove useful. Unfortunately, no such single compound
has yet been identified, as the changes taking place in a sample of meat during
storage are contingent on numerous factors. On the other hand, a combination of
volatile compounds may form a unique 'fingerprint' which can be analysed pattern
recognition algorithms with an electronic nose. It can supplement established
techniques of meat quality assessment by providing results that correlate well
with hedonic perception in a short time and at a low cost.
PMID- 28501438
TI - Investigating drug absorption from the colon: Single-pass vs. Doluisio approaches
to in-situ rat large-intestinal perfusion.
AB - Traditionally, the colon is considered a secondary intestinal segment in the drug
absorption process. However, in many cases the role of colonic drug permeability
cannot be overlooked. The purpose of this research was to compare colon
permeability data obtained using two different rat perfusion methods the single
pass intestinal perfusion (SPIP) approach and the closed-loop (Doluisio)
perfusion model. A list of 14 structurally diverse model drugs was constructed,
and their rat colon permeability was studied using the two methods. The two sets
of results were compared to each other, and were evaluated vs. in-vitro, ex-vivo,
and in-vivo literature values. The SPIP and the Doluisio results exhibited good
correlation between them (R2=0.81). The best correlation of both sets was
obtained with transport studies across Caco-2 monolayers (R2~0.9), as well as the
sigmoidal fit vs. human fraction of dose absorbed (Fabs) data. On the other hand,
Ussing chambers data, as well as lipophilicity (Log P) data, resulted in weak
correlation to the in-situ results. In conclusion, the single-pass intestinal
perfusion (SPIP) and the Doluisio (closed-loop) perfusion models were found to be
equally convenient and useful for obtaining validated colon permeability values,
although more human colonic Fabs data are needed for a better understanding of
colonic drug permeability and absorption.
PMID- 28501439
TI - Paclitaxel: What has been done and the challenges remain ahead.
AB - In recent years, the nanotechnology has offered researchers the opportunity to
solve the problems caused by the vehicle of the standard and first formulation of
paclitaxel (Taxol(r)), while maximizing the proven antineoplastic activity of the
drug against many solid tumors. Hence, different types of nanocarriers have been
employed to improve the efficacy, safety, physicochemical properties and
pharmacokinetic/pharmacodynamic profile of this drug. To date, paclitaxel is the
unique drug that is marketed in three different nanoplatforms for its parenteral
delivery: polymeric nanoparticles (Abraxane(r)), liposomes (Lipusu(r)), and
polymeric micelles (Genexol(r), Nanoxel(r) and Paclical(r)). Indeed, a fourth
nanocarrier might be available soon, because phase III studies of OpaxioTM, a
polymeric-conjugated, are near completion. Furthermore, other several
nanoformulations are currently in various stages of clinical trials. Therefore,
it is only through the critical analysis of clinical evidence from these studies
that we can get a more concrete idea of what has been achieved with
pharmaceutical nanotechnology so far. This review attempts to summarize current
information available regarding the clinical status and the physicochemical
characteristic of different nanocarriers for paclitaxel delivery in cancer
therapy. We present an overview of the preclinical and clinical data of these
systems including their pharmacokinetics, dose and administration, adverse events
and clinical efficacy.
PMID- 28501440
TI - Classification of microcrystalline celluloses via structures of individual
particles measured by synchrotron radiation X-ray micro-computed tomography.
AB - Microcrystalline cellulose (MCC) is one of the most important excipients due to
its outstanding binding and tableting properties. Owing to the absence of high
resolution characterization techniques at the single particle scale, 3D (three
dimension) microstructure of MCC and its effects on formulation performance
remain unexamined. The aim of this work was to establish a methodology for single
particles of MCC type 102 based on synchrotron radiation X-ray micro computed
tomography (SR-MUCT), principal component analysis (PCA) and partial least square
discriminant analysis (PLSDA). Scanning electron microscopy, SR-MUCT, powders
properties together with tensile strength (TS), disintegration time (DT),
Kawakita plots and force/displacement profiles of tablets were measured. PCA
PLSDA was applied to evaluate the structural classification of MCC particles on
the basis of 2D and 3D SR-MUCT derived images. The studied MCCs were found to
differ in the TS, DT, Kawakita plot and force/displacement, while box ratio and
Feret ratio had major influence on the principal components, but the angle of
repose, bulk and tapped density did not exhibit significantly. These findings
verified that different samples of MCCs from alternative suppliers have
morphological diversity when assessed at the individual particle level, which
could result into variation in powder properties and tableting performance.
PMID- 28501441
TI - Repeatability of topographic corneal thickness in keratoconus comparing VisanteTM
OCT and Oculus Pentacam HR(r) topographer.
AB - PURPOSE: To assess the repeatability and reproducibility of VisanteTM OCT and
Oculus Pentacam HR(r) in measuring central (CCT) and topographic corneal
thickness (TCT) along the principle meridians in keratoconus (KC) corneae.
METHOD: Twenty participants diagnosed with KC were recruited. There were two
study visits. On the first study visit, two repeated corneal thickness
measurements were obtained with each instrument. Measurements were repeated at
least 48hrs later in the same order. TCT were recorded in the 90, 180, 45 and 135
meridians at 1mm intervals across 8mm chord. RESULTS: Mean CCT for VisanteTM OCT
was 484.97+/-43.14MUm (range: 484.84-486.09) and Oculus Pentacam HR(r) was
478.86+/-45.31MUm (range: 477.20-480.53). No significant difference in TCT
between the two visits (p=0.54) and measurements (p=0.63) for VisanteTM OCT. For
Oculus Pentacam HR(r), no significant difference was found for each visit
(p=0.18) but differences existed in the measurements outside of the central
region (p=0.001). Tukey post-hoc analysis shows the differences (p?0.05) were
found in the +1 and +4 (supero-temporal) locations in the 135 meridian.
Significant differences were found comparing the two instruments, (p<0.05). Bland
Altman plots were used to demonstrate the differences between the two instruments
and indicate their limits of agreement. CONCLUSION: Both instruments gave
repeatable measurements as no significant differences were found in most
locations in all meridians. Comparing the two instruments, they were not
reproducible in all locations.
PMID- 28501442
TI - Theoretical fitting characteristics of typical soft contact lens designs.
AB - PUROSE: To calculate theoretical fitting success rates (SR) for a range of
typical soft contact lens (SCL) designs using a mathematical model. METHOD: A
spreadsheet mathematical model was used to calculate fitting SR for various SCL
designs. Designs were evaluated using ocular topography data from 163 subjects.
The model calculated SR based on acceptable edge strain (within range 0-6%) and
horizontal diameter overlap (range 0.2-1.2mm). Where lenses had multiple base
curves (BCs), eyes unsuccessful with the steeper BC were tested with the flatter
BC and aggregate SR calculated. Calculations were based on typical, current,
hydrogel and silicone hydrogel SCLs and allowed for appropriate on-eye shrinkage
(1.0-2.3%). Theoretical results were compared with those from actual clinical
trials. RESULTS: Theoretical success rates for one-BC lenses ranged from 60.7%
(95% CI 7.2%) to 90.2% (95% CI 3.7%). With two-BC designs, most combinations
showed a SR increase with a second BC (84.0%-90.2%). However, one of the two-BC
combinations showed only negligible increase with a second BC (72.4%-73.0%). For
designs with lower SR, the greatest contributor to failure was inadequate lens
diameter. For a given design, differences in shrinkage (i.e. on-eye bulk
dehydration) had a significant effect on success rate. In comparison with
historical clinical data, there was a positive correlation between small lens
fitting prevalence and discomfort reports (r=+0.95, P=<0.001) with a poor
correlation between theoretical and actual tight/loose fittings. CONCLUSIONS:
Mathematical modelling is a useful method for testing SCL design combinations.
The results suggest that judicious choice of additional fittings can expand the
range of fitting success.
PMID- 28501443
TI - Meibomian gland dysfunction and its determinants in Iranian adults: A population
based study.
AB - PURPOSE: To estimate the prevalence of Meibomian gland dysfunction (MGD) and
determine the associated factors in the general population in Iran. METHODS: This
cross-sectional study is based on the data from the second phase of the Shahroud
Eye Cohort Study conducted in 2014. Of the 4737 participants of the second phase,
data was available for 4700 people; their mean age was 55.9+/-6.2 years and 2768
(58.9%) were women. Diagnosis of MGD was made based on the classification of the
International Workshop on MGD as judged by the examining ophthalmologist. The
prevalence of MGD was summarized as percentage and 95% confidence intervals (CI),
and related factors were studied through simple and multiple logistic
regressions. RESULTS: The diagnosis of MGD in at least one eye was recorded for
1235 (26.3%) participants; the prevalence of unilateral and bilateral MGD was
26.3% (95% CI: 24.5-28.1) and 26.1% (95% CI: 24.3-27.9), respectively. In the
multiple logistic regression analyses, MGD significantly correlated with
pinguecula [odds ratio (OR)=1.3, 95% CI: 1.12-1.50], hypertension (OR=1.34, 95%
CI: 1.11-1.61), high-density lipoprotein (HDL) level (OR=0.0992, 95% CI: 0.986
0.999), diabetes mellitus (OR=0.83, 95% CI: 0.71-0.97), and years of education
(OR=0.98, 95% CI: 0.96-0.99). CONCLUSIONS: MGD prevalence in this study was lower
than the rates reported in other studies on Asian populations. Besides HDL level,
MGD is associated with another ocular surface disorder, namely pinguecula, as
well as certain systemic diseases such as hypertension and diabetes mellitus.
These associations should be taken into consideration when diagnosing MGD.
PMID- 28501444
TI - Modern scleral lenses: Mini versus large.
AB - The evolution of scleral lenses has led to new formulations of scleral fitting
concepts and designs. The diameters of modern scleral lenses have been overhauled
too and they are smaller comparing to the original ones. Nowadays, prescription
of mini-sclerals supposedly seems in major extension and it appears indeed the
necessity of some practitioner to differentiate the smaller mini-scleral lenses
from larger mini-scleral lenses empathizing that they are the "smaller" ones.
Therefore, it is maybe, necessary a definition of mini-scleral lenses referring
to the landing zone width in relation to the horizontal visible iris diameter
(HVID) and the limbus extension. The choice of the total diameter is crucial for
a successful fitting and it depends majorly on patient's topographic patterns and
anatomic factors. However, there are other important criteria for the selection
of the scleral lens diameter based on oxygen supply, bubbles formation,
mechanical stress on a toric sclera, ocular surface disease protection, entity of
the vault over the cornea and distribution of the lens weight on the sclera. The
advantages of mini-scleral lenses are various nonetheless in some cases large
lenses are necessary. This paper presents a review of the benefits and
disadvantages of both mini and large scleral lenses analyzing the conditions in
which it may be better to prefer one diameter to another. A suggestion may be
that to start fitting the smallest lens as possible, depending on the dimension
of HVID and limbus width and consider larger lenses only when issues occur.
PMID- 28501445
TI - Local and systemic humoral immune response in farmed Atlantic salmon (Salmo salar
L.) under a natural amoebic gill disease outbreak.
AB - Amoebic gill disease (AGD), caused by the protozoan parasite Neoparamoeba
perurans, is one of the most significant infectious diseases for Atlantic salmon
(Salmo salar L.) mariculture. The present study investigated the humoral immune
response (both local in gill mucus and systemic in serum) of farmed Atlantic
salmon naturally infected with N. perurans in commercial sea pens, at two
different stages of the disease and after freshwater treatment. Parameters
analysed included activity of immune related enzymes (i.e. lysozyme, peroxidase,
protease, anti-protease, esterase, alkaline phosphatase), IgM levels, and the
terminal carbohydrate profile in the gill mucus. Overall, greater variations
between groups were noted in the immune parameters determined in gill mucus than
the equivalent in the serum. In gill mucus, IgM levels and peroxidase, lysozyme,
esterase and protease activities were decreased in fish showing longer exposure
time to the infection and higher disease severity, then showed a sequential
increase after treatment. Results obtained highlight the capacity of gills to
elicit a local response to the infection, indicate an impaired immune response at
the later stages of the disease, and show partial reestablishment of the host
immune status after freshwater treatment. In addition to providing data on the
humoral response to AGD, this study increases knowledge on gill mucosal humoral
immunity, since some of the parameters were analysed for the first time in gill
mucus.
PMID- 28501446
TI - The involvement of cathepsin F gene (CTSF) in turbot (Scophthalmus maximus L.)
mucosal immunity.
AB - Cathepsin F (CTSF) is a recently described papain-like cysteine protease and
unique among cathepsins due to an elongated N-terminal pro-region, which contains
a cystatin domain. CTSF likely plays a regulatory role in processing the
invariant chain which is associated with the major histocompatibility complex
(MHC) class II. In this regard, we identified the CTSF gene of turbot as well as
its protein structure, phylogenetic relationships, and expression patterns in
mucosal tissues following Vibrio anguillarum and Streptococcus iniae challenge.
We also determined the expression patterns of CTSF in mucosal tissues after
vaccinated with the formalin-inactivated V. vulnificus whole-cell vaccine.
Briefly, turbot CTSF gene showed the closest relationship with that of
Paralichthys olivaceus in phylogenetic analysis. And CTSF was ubiquitously
expressed in all tested tissues with the highest expression level in gill. In
addition, CTSF gene showed different expression patterns following different
bacterial challenge. The significant quick regulation of CTSF in mucosal surfaces
against infection indicated its roles in mucosal immunity. Functional studies
should further characterize avail utilization of CTSF function to increase the
disease resistance of turbot in maintaining the integrity of the mucosal barriers
against infection and to facilitate selection of the disease resistant
family/strain in turbot.
PMID- 28501447
TI - Comparison of quantitative measurement of foveal avascular zone and macular
vessel density in eyes of children with amblyopia and healthy controls: an
optical coherence tomography angiography study.
AB - PURPOSE: To quantify vessel density of superficial capillary plexus (SCP), deep
capillary plexus (DCP), and the foveal avascular zone (FAZ) of children's
amblyopic eyes and to compare the measurements with those of companion eyes and
age-matched controls. METHODS: Fifteen patients with strabismic amblyopia, and 15
age-matched controls were included in this cross-sectional study. SCP, DCP, and
FAZ were measured via optical coherence tomographic angiography (OCTA). RESULTS:
Mean subject age was 8.2 +/- 2.3 years in the amblyopia group and 8.6 +/- 2.2
years in the control group. The mean SCP at 1 mm, 2 mm, and 3 mm zones were (in
the order amblyopic eye, companion eye, control) 1.399 +/- 0.088, 5.854 +/-
0.195, 12.866 +/- 0.346; 1.467 +/- 0.084, 5.979 +/- 0.182, 12.965 +/- 0.321; and
1.559 +/- 0.052, 6.343 +/- 0.190, 13.819 +/- 0.423. SCP was significantly lower
in amblyopic eyes than in companion eyes and controls (P < 0.05). The mean DCP at
1 mm, 2 mm, and 3 mm zones were 1.425 +/- 0.069, 6.038 +/- 0.186, 13.522 +/-
0.336; 1.525 +/- 0.072, 6.427 +/- 0.190, 14.286 +/- 0.322; and 1.685 +/- 0.074,
6.895 +/- 0.198, 15.355 +/- 0.356. DCP was significantly lower in amblyopic eyes
than companion eyes and controls (P < 0.05). The mean superficial FAZ were 0.287
+/- 0.091, 0.262 +/- 0.092, and 0.280 +/- 0.097. The mean deep FAZ were 0.382 +/-
0.092, 0.335 +/- 0.080, and 0.329 +/- 0.085. There was no significant difference
in FAZ among groups (P > 0.05). CONCLUSIONS: Vessel density of SCP and DCP of
eyes with amblyopia is lower than that of the companion eye and the age-matched
controls.
PMID- 28501448
TI - Pseudomonas versuta sp. nov., isolated from Antarctic soil.
AB - In this study we analysed three bacterial strains coded L10.10T, A4R1.5 and
A4R1.12, isolated in the course of a study of quorum-quenching bacteria occurring
in Antarctic soil. The 16S rRNA gene sequence was identical in the three strains
and showed 99.7% pairwise similarity with respect to the closest related species
Pseudomonas weihenstephanensis WS4993T. Therefore, the three strains were
classified within the genus Pseudomonas. Analysis of housekeeping genes (rpoB,
rpoD and gyrB) sequences showed similarities of 84-95% with respect to the
closest related species of Pseudomonas, confirming its phylogenetic affiliation.
The ANI values were less than 86% to the closest related species type strains.
The respiratory quinone is Q9. The major fatty acids are C16:0, C16:1 omega7c/
C16:1 omega6c in summed feature 3 and C18:1 omega7c / C18:1 omega6c in summed
feature 8. The strains are oxidase- and catalase-positive. Growth occurs at 4-30
degrees C, and at pH 4.0-10. The DNA G+C content is 58.2-58.3mol %. The combined
genotypic, phenotypic and chemotaxonomic data support the classification of
strains L10.10T, A4R1.5 and A4R1.12 into a novel species of Pseudomonas, for
which the name P. versuta sp. nov. is proposed. The type strain is L10.10T (LMG
29628T, DSM 101070T).
PMID- 28501449
TI - Initial Steps in Training the Public about Bleeding Control: Surgeon
Participation and Evaluation.
AB - BACKGROUND: With increasing active shooter and intentional mass casualty events,
as well as everyday injuries resulting in severe bleeding, there have been calls
for the public to learn bleeding control techniques. The aims of this project
were to offer bleeding control training to surgeons attending the Clinical
Congress of the American College of Surgeons (ACS), to determine if the trained
surgeons believe that teaching bleeding control to the public should be a
priority of the ACS, and to assess the surgeon trainees' perceptions regarding
the appropriateness of the course for a public audience. STUDY DESIGN: This was
an educational program with a post-course evaluation to determine if the bleeding
control course is appropriate for a public audience. RESULTS: Three hundred forty
one surgeons were trained. All were trained and successfully performed a return
demonstration. Regarding perceptions of the participating surgeons that teaching
bleeding control to the public should be a priority of the ACS, 93.79% of the 322
surgeons responding indicated agreement with this proposition. Regarding whether
or not the training was at an appropriate level of difficulty for the public,
93.13% of the 320 respondents to this item agreed that it was appropriate.
CONCLUSIONS: The surgeons who were trained were very much in favor of making
training the public a priority of the ACS. With additional training of surgeons
and other health care professionals as trainers, and the engagement of the
public, the goal of having a citizenry prepared to stop bleeding can be achieved.
PMID- 28501450
TI - Exploring prognosis in chronic relapsing visceral leishmaniasis among HIV
infected patients: Circulating Leishmania DNA.
AB - BACKGROUND: Visceral leishmaniasis (VL) affecting HIV-infected patients is
considered a challenging condition because of its high mortality and relapse
rates. The approach of this condition is still surrounded by many uncertainties,
especially regarding the criteria to institute and discontinue secondary
prophylaxis for VL. The aim of this study was to evaluate the Leishmania
parasitism kinetic assessed by polymerase chain reaction (PCR) as a possible tool
in the prognostic assessment in a context in which patients are receiving highly
active antiretroviral therapy and secondary prophylaxis. METHODS: A prospective
observation of Leishmania-HIV-co infected patients was performed and two groups
with distinct clinical prognosis unpredicted by their CD4 count at the moment of
VL diagnosis and not related to their HIV load control were confirmed. RESULTS:
Relapsing (R) and non-relapsing (NR) patients had similar antiviral therapy use
rates, CD4 lymphocyte count medians and HIV load levels at VL-diagnosis. At the
12-month follow-up, R-patients presented a significantly lower CD4 lymphocyte
count than NR-patients, without difference in HIV load control. The time between
HIV and VL diagnoses was longer in the R than NR-group. Comparison between Kaplan
Meier relapse-free survival curves (time to relapse) using a log rank test showed
that patients presenting circulating Leishmania DNA had a significantly higher
risk of clinical VL relapse within 4 months after a positive test (p=0.001).
CONCLUSIONS: These results reinforce that a negative PCR could be a useful tool
to support prophylaxis interruption among patients with CD4 counts above
200cells/mm3 and that a positive PCR suggests imminent VL relapse.
PMID- 28501452
TI - Promoting Same-Day Discharge for Gynecologic Oncology Patients in Minimally
Invasive Hysterectomy.
AB - STUDY OBJECTIVE: Despite clear data demonstrating feasibility, safety, and cost
effectiveness of same-day discharge after minimally invasive hysterectomy, a
paucity of data suggests ways to increase same-day discharge rates. Our
objectives were to promote same-day discharge after minimally invasive
hysterectomy using preoperative patient education videos, provider same-day
discharge awareness initiatives, and standardization of postoperative management
and to investigate reasons for overnight admission after surgery (non-same-day
discharge). DESIGN: A quality improvement project measured rates of same-day
discharge, patient satisfaction, and readmission during the 5 months before and
after video implementation. Readmission rates were calculated as a surrogate for
safety. A retrospective chart review was conducted of patients who underwent
minimally invasive hysterectomy during the 5 months after video implementation,
comparing 43 same-day discharges to 26 non-same-day discharge patients who met
criteria for same-day discharge. Differences between groups were analyzed using 2
tailed t tests or logistic regression (continuous variables) and Fisher's exact
test or chi2 test (categorical variables). Next, providers were educated about
same-day discharge, and initiatives were implemented to standardize postoperative
care. Same-day discharge rates were then calculated to evaluate these additional
interventions (Canadian Task Force classification II-2). SETTING: A gynecologic
oncology division based at an academic institution and performing surgery at 2
hospitals. PATIENTS: All patients undergoing minimally invasive hysterectomy for
both benign and malignant disease, using robot-assisted, straight laparoscopic,
and radical hysterectomy procedures. INTERVENTIONS: Patient education video,
provider education about same-day discharge, and initiatives to standardize
postoperative care. MEASUREMENTS AND MAIN RESULTS: Overall, same-day discharge
rates decreased from 47% to 35% and readmission rates from 1.7% to 0% after video
implementation. Greater than 87% of both groups were very or somewhat satisfied
with their care (p = .71). Excluding patients who did not qualify for same-day
discharge, the prevideo implementation same-day discharge rate was 72% (n = 78)
and the postvideo implementation same-day discharge rate was 62% (n = 69). Higher
patient complexity (p = .003), later case end time (p = .001), longer operative
time (p = .001), and robot-assisted cases (p = .002) significantly predicted non
same-day discharge. After implementing initiatives to increase provider same-day
discharge awareness and to standardize postoperative management, in addition to
video implementation, the same-day discharge rate increased to 86% (n = 51).
CONCLUSION: Same-day discharge in a select population is safe and feasible, with
at least similar patient satisfaction as non-same-day discharge patients. Shorter
operative time, earlier case end time, lower patient complexity, and non-robot
assisted approach increase the likelihood of same-day discharge. Patient
education videos alone did not increase same-day discharges but maintained
acceptable readmission rates. Communication with providers regarding the same-day
discharge initiative and standardization of postoperative management with
preoperative video implementation may lead to increased same-day discharge rates.
PMID- 28501453
TI - Is fine-needle aspiration a reliable tool in the diagnosis of malignant salivary
gland tumors?
AB - PURPOSE: The purpose of the present study was to establish the reliability of
fine needle aspiration (FNA) in the diagnosis of malignant salivary gland tumors
in our population and to compare our results with those of other authors.
MATERIAL AND METHODS: This was a retrospective study of clinical data from 172
patients, 153 parotid tumors and 19 submandibular tumors who underwent
preoperative FNA between January 2004 and December 2013. Sensitivity,
specificity, positive and negative predictive values of FNA for the preoperative
diagnosis of malignancy were analyzed. RESULTS: For the diagnosis of malignancy
an S value of 60% was obtained, which means that 40% of malignant tumors were not
diagnosed by FNA. Besides an E value of 97.5% was obtained, thus indicating that
FNA was negative for malignancy in up to 97.5% of all benign neoplasms. According
to predictive values, we observe that FNA hit in 83.3% cases given as malignant
and in 92% of cases giving as benign (PPV=83,3%; NPV=92%). CONCLUSION: With a
scarce 60% sensitivity value in our series, fine needle aspiration has evident
limitations for diagnosis of malignancy in major salivary gland neoplasms. Being
highly conditioned by the staff and the conditions in which it is performed, FNA
is a complementary test that helps the preoperative diagnosis of the major
salivary glands with radiological tests, medical history and physical
examination, but that alone it is not defining of malignancy.
PMID- 28501454
TI - Masseteric nerve for gracilis muscle re-innervation in unilateral facial palsy:
Impact on quality of life.
AB - BACKGROUND: Unilateral established or congenital facial palsies are usually
treated with neuromuscular transplantation to reanimate the impaired side of the
face. One of the most debated points is the motor nerve to choose for the
reinnervation of the transplant. Contra-lateral healthy facial nerve is usually
preferred, but in selected cases motor nerve to masseter is considered a valuable
option. However only a few clinical studies focused on quality of life in this
subset of patients are available in literature. METHODS: Twenty patients treated
for established or congenital unilateral facial palsy reanimated with gracilis
muscle transplant reinnervated with masseteric nerve were retrospectively
analyzed. The FDI questionnaire on quality of life was administered before and
after surgery and statistical analysis of results was conducted to score changes.
RESULTS: Overall results of the questionnaire resulted in a statistically
significant improvement after surgery, with a p value of 0.05. CONCLUSION: Facial
animation with gracilis muscle transplant re-innervated with masseteric nerve is
a safe and reliable procedure in selected unilateral facial palsy patients.
Results reported here confirm that surgery mainly improves the functional aspects
of a patient's daily life quality, while the impact on social interactions and
self-perception is less significant. The comparison of these results with those
obtained in patients treated with gracilis muscle transplant re-innervated via
contralateral facial nerve suggests that spontaneity is probably highly relevant
to improve social aspects of QOL in this subset of patients.
PMID- 28501451
TI - Habitual exercise levels are associated with cerebral amyloid load in
presymptomatic autosomal dominant Alzheimer's disease.
AB - INTRODUCTION: The objective of this study was to evaluate the relationship
between self-reported exercise levels and Alzheimer's disease (AD) biomarkers, in
a cohort of autosomal dominant AD mutation carriers. METHODS: In 139
presymptomatic mutation carriers from the Dominantly Inherited Alzheimer Network,
the relationship between self-reported exercise levels and brain amyloid load,
cerebrospinal fluid (CSF) Abeta42, and CSF tau levels was evaluated using linear
regression. RESULTS: No differences in brain amyloid load, CSF Abeta42, or CSF
tau were observed between low and high exercise groups. Nevertheless, when
examining only those already accumulating AD pathology (i.e., amyloid positive),
low exercisers had higher mean levels of brain amyloid than high exercisers.
Furthermore, the interaction between exercise and estimated years from expected
symptom onset was a significant predictor of brain amyloid levels. DISCUSSION:
Our findings indicate a relationship exists between self-reported exercise levels
and brain amyloid in autosomal dominant AD mutation carriers.
PMID- 28501455
TI - Exploring the acceptability of the available pneumococcal conjugate vaccines in
Canadian health care professionals and immunization experts.
AB - BACKGROUND: In children, the 13 and 10-valent pneumoccocal conjugate vaccines
(PCV13/10) are currently approved for the prevention of invasive pneumococcal
disease (IPD). Acceptability is a key consideration in the implementation of a
vaccine program and it is recognized that health professional's attitudes and
opinions towards vaccines are independent predictors of the success of an
immunization program. We aimed to survey the beliefs and attitudes for the two
available PCVs in health care professionals and immunization experts. FINDINGS:
We interviewed 21 members of Canadian immunization committees and/or participants
working in frontline healthcare delivery. Overall, participants predominantly
preferred PCV-13 over PCV10. For most, AOM should not be taken into
considerations in decisions for pneumococcal vaccination programs implementation.
AOM was considered an important endpoint of the program but an ineffective
measure of program success due to the lack of surveillance for the condition.
Recent evidence pertaining to PCV10 cross-protection against 19A did not affect
preference but had an impact on perceptions regarding pricing. CONCLUSION: To
consider implementing any changes to the current program, most participants would
require more evidence regarding PCV10 cross-protection and effectiveness against
OM. Decreasing vaccine price was cited as a positive outcome of funding both
vaccines.
PMID- 28501457
TI - Pushing Bacterial Biohybrids to In Vivo Applications.
AB - Bacterial biohybrids use the energy of bacteria to manipulate synthetic materials
with the goal of solving biomedical problems at the micro- and nanoscale. We
explore current in vitro studies of bacterial biohybrids, the first attempts at
in vivo biohybrid research, and problems to be addressed for the future.
PMID- 28501456
TI - Assessing age-dependent susceptibility to measles in Japan.
AB - BACKGROUND: Routine vaccination against measles in Japan started in 1978. Whereas
measles elimination was verified in 2015, multiple chains of measles transmission
were observed in 2016. We aimed to reconstruct the age-dependent susceptibility
to measles in Japan so that future vaccination strategies can be elucidated.
METHODS: An epidemiological model was used to quantify the age-dependent immune
fraction using datasets of vaccination coverage and seroepidemiological survey.
The second dose was interpreted in two different scenarios, i.e., booster and
random shots. The effective reproduction number, the average number of secondary
cases generated by a single infected individual, and the age at infection were
explored using the age-dependent transmission model and the next generation
matrix. RESULTS: While the herd immunity threshold of measles likely ranges from
90% to 95%, assuming that the basic reproductive number ranges from 10 to 20, the
estimated immune fraction in Japan was below those thresholds in 2016, despite
the fact that the estimates were above 80% for all ages. If the second dose
completely acted as the booster shot, a proportion immune above 90% was achieved
only among those aged 5years or below in 2016. Alternatively, if the second dose
was randomly distributed regardless of primary vaccination status, a proportion
immune over 90% was achieved among those aged below 25years. The effective
reproduction number was estimated to range from 1.50 to 3.01 and from 1.50 to
3.00, respectively, for scenarios 1 and 2 in 2016; if the current vaccination
schedule were continued, the reproduction number is projected to range from 1.50
to 3.01 and 1.39 to 2.78, respectively, in 2025. CONCLUSION: Japan continues to
be prone to imported cases of measles. Supplementary vaccination among adults
aged 20-49years would be effective if the chains of transmission continue to be
observed in that age group.
PMID- 28501458
TI - In Vivo Molecular Bioluminescence Imaging: New Tools and Applications.
AB - in vivo bioluminescence imaging (BLi) is an optical molecular imaging technique
used to visualize molecular and cellular processes in health and diseases and to
follow the fate of cells with high sensitivity using luciferase-based gene
reporters. The high sensitivity of this technique arises from efficient photon
production, followed by the reaction between luciferase enzymes and luciferin
substrates. Novel discoveries and developments of luciferase reporters,
substrates, and gene-editing techniques, and emerging fields of applications,
promise a new era of deeper and more sensitive molecular imaging.
PMID- 28501459
TI - [Cancer, radiotherapy and immune system].
AB - Novel paradigms emerge in oncology today. Systemic treatments are more effective
and diversified along with an increased life expectancy in oligometastatic
patients. Stereotactic radiotherapy using hypofractionation opens new
perspectives for local tumour control. The area of radiobiology has expanded with
integration of tumour microenvironment in which radiation-induced inflammation
mediators and immune system play a major role. Immunity checkpoints inhibitors
experience a major development. This rapidly evolving field seems involved in the
abscopal effects, especially when radiation is combined with checkpoints
inhibitors, as demonstrated in numerous preclinical studies and several clinical
trials. Paradoxically, irradiation also produces immunosuppressive effects. This
manuscript aims to report the dual effects of ionizing radiation on the immune
system and reviews some results of the combination of radiation and immunity
chekpoints inhibitors and also research perspectives.
PMID- 28501460
TI - Involvement of JNK signaling in IL4-induced M2 macrophage polarization.
AB - It has been generally accepted that alternatively activated macrophages (M2),
which can be induced by type 2 cytokines such as IL-4, is responsible for tissue
repair. However, the function of JNK in IL-4-induced M2 macrophage polarization
remains unclear. Here, we demonstrated that M0 macrophages can be polarized into
M2 status in response to IL-4 stimulation with the increased expression of the M2
specific molecular markers. We also found that IL-4 induced higher expression of
JNK and transcription factor c-Myc in M2 macrophages. Our Q-PCR and Western blot
results showed that JNK increased the expression of c-Myc and M2 markers Arg1,
Mrc1. We also demonstrated c-Myc was the downstream of IL-4-JNK pathway. Further,
the depletion of c-Myc, Arg1 and Mrc1 could inhibit the migration ability of M2
macrophages. Taken together, our data establishes a new role for JNK signaling in
IL-4-induced alternative activation of macrophages and may provide a novel
strategy for immune therapy.
PMID- 28501461
TI - Spliceosome-associated factor CTNNBL1 promotes proliferation and invasion in
ovarian cancer.
AB - Ovarian cancer is the most lethal gynecologic malignancy and the molecular
pathogenesis of high-grade serous ovarian carcinoma has not been completely
characterized. Numerous studies have shown that altered splicing patterns and
splicing factors were found to contribute to tumor development and progression.
In this study, we demonstrated that spliceosome-associated factor CTNNBL1 was
significantly upregulated in high-grade serous ovarian carcinoma, the elevated
level of CTNNBL1 indicates poor prognosis in patients with high-grade serous
ovarian carcinoma. Functional characterization revealed that CTNNBL1 promoted the
proliferation and invasion of ovarian cancer cells in vitro. Furthermore, through
transcriptome analysis, we found CTNNBL1 regulates multiple splicing events and
gene expression in ovarian cancer cells. Importantly, we identified IFI16 and
FOXM1 splicing was regulated by CTNNBL1. To our knowledge, this is the first
study exploring the expression, functional roles and regulated splicing events of
CTNNBL1 in ovarian cancer.
PMID- 28501462
TI - Ray resection in paediatric population.
AB - AIM: Evaluation of clinical and functional outcome of ray resection in paediatric
population and description of key aspects of surgical technique. MATERIAL AND
METHODS: We performed a retrospective review of all patients undergoing surgery
between 2010-2015. INCLUSION CRITERIA: one or more ray resections of the hand and
a minimum of one year follow-up. Evaluation of clinical characteristics,
functional and cosmetic results, complications, need for psychological support
and patient or family satisfaction. RESULTS: Four patients met the inclusion
criteria. The mean age at surgery was 5 years (range, 1-14 years). Aetiology was:
fibrolipomatous hamartoma, traumatic amputation, radial deficiency and complex
syndactyly. Second ray was resected in three patients and third and fourth ray in
one. No finger transfer was performed. No immediate post-operative complications
were found at the final evaluation. None of them needed psychological support.
All the patients showed excellent clinical and functional results with a high
grade of satisfaction. DISCUSSION: Ray resection of the hand has been used as
salvage procedure in patients with vascular lesions, tumours, trauma, infections
or congenital malformations. There are only a few published studies including
small samples in adults or case reports, with no references in the paediatric
population. CONCLUSION: Ray resection of the hand is a useful and safe technique
in paediatric population, obtaining excellent cosmetic and functional results in
those cases in which it is impossible to preserve one or more fingers.
PMID- 28501463
TI - Home-based rehabilitation in the postoperative treatment of flexor tendon repair.
AB - OBJECTIVE: To evaluate the results and complications of flexor tendon repair in
which a home-based rehabilitation program was utilized without the assistance of
a hand therapist during the first 4postoperative weeks. MATERIAL Y METHODS:
Between July 2009 and July 2014, a total of 21 digits in 15 patients were treated
in our institution for complete laceration of the flexor tendons within the
flexor pulley system (zone 1 and 2). Passive and active exercises performed by
the patients themselves were started the morning after the operation. Data, as
range-of-motion and complications, were collected 6months after the surgery.
RESULTS: Fifteen digits had full recovery of flexion. One patient suffered a
rupture in the fifth postoperative week. Ten of the 21 digits developed a flexion
contracture of the proximal interphalangeal joint; in 5 the contracture was less
or equal to 10 degrees without impairment of function or aesthetics. DISCUSSION:
Over recent decades, specialized hand therapy has been of great importance in the
postoperative treatment of hand diseases. Unfortunately, these professionals are
not always available in our area in the first days after surgery. With this
protocol, the patient is in charge of carrying out the postoperative exercises,
which could lead to a worse final result and a higher rate of complications.
CONCLUSION: The home-based rehabilitation program yielded complete recovery of
joint mobility in most cases with a low complication rate.
PMID- 28501464
TI - The connection between nursing diagnosis and the use of healthcare resources.
AB - AIM: The health service invests up to 75% of its resources on chronic care where
the focus should be on caring rather than curing. Nursing staff focuses their
work on such care. Care requires being redorded in health histories through the
standardized languages. These records enable useful analyses to organisational
and healthcare decision-making. Our proposal is to know the association of
between nursing diagnosis and a higher total expenditure on health. METHOD: An
observational cross-sectional analytical study was performed based on data from
electronic health records in Primary Care (Drago-AP), hospital discharges (CMBD
AH) and prescriptions (REC-SCS) of patients over 50 from 2012-2013 in the Canary
Islands. A descriptive, bivariate and multivariate analysis was undertaken to
create a predictive model on the use of resources. INDEPENDENT VARIABLES:
Sociodemographic (age, sex, type of health-care affiliation, type of prescription
charge) and nursing diagnosis (ND) recorded in late 2012. Dependent variables:
Resources consumed in 2013. RESULTS: 582,171 patients met the criteria for
inclusion. 53.0% of them were women with an average age of 64.3 years (SD
10.8years). 53.2% were pensioners. 49% of the included population had an ND, with
an average of 2.1ND per patient. The average costs per patient were 1824.62?
(with a median of 827.5?) 25 and 27 percentiles of 264.1? and 1824.7?,
respectively. The bivariate analysis showed a significant correlation between
these expenses and all the demographic variables; the expenses increased when a
nursing diagnosis has been made (Spearman's rank=0.37: the more diagnoses, the
more expenses). In the multivariate analysis, a first linear regression with the
sociodemographic variables as independent variables explains 13.7% of the
variability of the logarithm of the full costs (R2=0.137). If we add to this
model the presence of nursing diagnoses, the explanatory capacity reaches 19.77%
(R2=0.1977). CONCLUSION: Compared with a model that only consists of
sociodemographic variables, nursing diagnoses can enhance the explanatory
capacity of the use of healthcare resources.
PMID- 28501465
TI - Candiduria: Evidence-based approach to management, are we there yet?
AB - Candiduria is considered one of the most controversial issues in patient
management. Neither the diagnosis nor the optimal treatment options are
standardized. This is further complicated by lack of defined laboratory criteria
for diagnosis as most of the studies were set for bacterial rather than fungal
urinary tract infection (UTI). Furthermore, since Candida species is a known
commensal of the genitourinary tract its presence in the urine sample adds
ambiguity to making a definitive diagnosis of candidal UTI. Guidelines for
diagnosis and management of candiduria have changed considerably over the past
decades. In 1960s, the condition was believed to be benign with no intervention
required. However, over the years new dimensions were added to address the issues
associated with candiduria until the latest Infectious Diseases Association of
America (IDSA) guidelines were published in 2009, which indicated that there was
an increase in the incidence of candiduria caused by more resistant non-Candida
albicans species. Further complicating the issue is the observation that
candiduria may be the only indicator of a more serious invasive candidiasis,
especially in immunocompromised patients. Long-term urinary catheterization is
considered to be the most significant risk factor for candiduria followed by
antibiotic use and diabetes. Strategies for management are based on the
evaluation of candiduria in the context of the clinical setting to determine its
relevance and make an appropriate decision about the need for antifungal therapy.
Fluconazole is the main drug used for its efficacy and least complications. Other
options include bladder irrigation with amphotericin B, flucytosine or parenteral
amphotericin B. Since azoles other than fluconazole and all echinocandins are
poorly excreted in urine they have been found to be less effective in candiduric
patients.
PMID- 28501466
TI - A case of bilateral otomycosis associated with Aspergillus flavus and A. terreus
in Taiwan.
AB - Otitis externa caused by fungi (otomycosis) occurs more commonly in tropical
areas with high moisture than in temperate regions. Bilateral otomycosis is,
however, rarely reported. In a case of bilateral otitis externa in a 56-year-old
male patient in Taiwan, direct microscopic examination of the cerumen as well as
isolation of strains indicated the presence of two Aspergillus species being
different in each of both ears. The species were identified by DNA sequence
comparisons and additional morphological confirmation of diagnostic
characteristics as Aspergillus flavus and Aspergillus terreus. The rarely
reported occurrence of two Aspergillus species in otitis of the same patient
deserves attention in other cases of otomycosis, particularly with respect to
potentially different resistances of different species against antifungals.
Treatment with nystatin/neomycin was not successful, but with clotrimazole was
effective.
PMID- 28501467
TI - Keratitis by a rare pathogen Colletotrichum gloeosporioides: A case report.
AB - Colletotrichum species have been reported infrequently as the cause of keratitis
or subcutaneous lesions. The patient we describe developed keratitis after ocular
trauma. The sample from the corneal scrapings grew Colletotrichum gloeosporioides
as identified from morphological characters and DNA sequence of the 'Internal
Transcribed Spacer' (ITS) region. The patient underwent topical application of
amphotericin-B followed by itraconazole and natamycin treatment. Simultaneous
oral voriconazole regimen leads to complete regression of corneal ulcer. This
report highlights the fact that early and accurate identification and therapy can
resolve keratitis caused by rare pathogen C. gloeosporioides.
PMID- 28501468
TI - [Tinea capitis: Main mycosis child. Epidemiological study on 10years].
AB - Despite the changes in their epidemiology, and the improving level of hygiene of
the population, tinea capitis is still considered a public health problem in our
country, and is the most common type of dermatophytosis in our country. The aim
of our study was to evaluate the epidemiological, clinical and mycological
features of tinea capitis in children encountered in the Tunis region. A
retrospective study concerned 1600 children aged 6 months to 15 years suspected
to have tinea capitis was conducted in Parasitology-Mycology laboratory, Rabta
hospital, over a 10-years period (2005-2014). Dermatophyte infections were
confirmed using scalp scrapings examinated with direct microscopy using potash at
30% and/or culture on Sabouraud medium agar. Tinea capitis diagnosis was
confirmed in 947 cases (59.18%). The sex ratio was 2.61 and the average age of
6.28 years with predominance in the age group of 4 to 8 years (52.27%). The most
common clinical presentation was ringworm (87.65%). Ringworm large plaque was
predominant (65.9%). Direct examination was positive in 884 cases (93.35%).
Microsporic tinea was the most frequent (63.25%) followed by trichophytic tinea
(29.78%). Positive cultures of dermatophytes were obtained in 912 cases (96.30%).
The following dermatophyte species were isolated: Microsporum canis (67%),
Trichophyton violaceum (31.68%), Trichophyton mentagrophytes (0.66%), Microsporum
audouinii (0.22%), Trichophyton schoenleinii (0.22%) and Microsporum gypseum
(0.22%). M. canis is currently the most frequently incriminated species in tinea
capitis in Tunisia. This change is related to a change in behavior of our
population, in fact the cat; main reservoir of M. canis cohabiting increasingly
with Tunisian families.
PMID- 28501469
TI - Routes for Drug Translocation Across the Blood-Brain Barrier: Exploiting Peptides
as Delivery Vectors.
AB - A number of potent drugs for the treatment of brain diseases are available.
However, in order for them to reach their target site of action, they must pass
the blood-brain barrier (BBB). The capillary endothelium comprises the major
barrier of the BBB and allows only passive permeation of some small lipophilic
molecules. Brain delivery of the larger biopharmaceuticals, which today includes
an increasing number of novel drug entities, is therefore restricted, both due to
their molecular size and their hydrophilic nature. Thus, the development of novel
drug entities intended for the treatment of brain diseases such as
neurodegenerative diseases or brain cancers require a delivery strategy for
overcoming the BBB before reaching its final target within the brain. Peptide
based delivery vector is an emerging tool as shuttles for drug delivery across
the BBB and one may explore receptor-mediated transcytosis, adsorptive-mediated
transcytosis, and the paracellular route. The latter, however, being
controversial due to the risk of co-delivery of blood-borne potential harmful
substances. On the other hand, a number of studies report on drug delivery across
the BBB exploiting receptor-mediated transcytosis and adsorptive-mediated
transcytosis, indicating that peptides and peptide vectors may be of use in a
central nervous system delivery context.
PMID- 28501470
TI - Possibility of Predicting Serotonin Transporter Occupancy From the In Vitro
Inhibition Constant for Serotonin Transporter, the Clinically Relevant Plasma
Concentration of Unbound Drugs, and Their Profiles for Substrates of
Transporters.
AB - Accurate prediction of target occupancy facilitates central nervous system drug
development. In this review, we discuss the predictability of serotonin
transporter (SERT) occupancy in human brain estimated from in vitro Ki values for
human SERT and plasma concentrations of unbound drug (Cu,plasma), as well as the
impact of drug transporters in the blood-brain barrier. First, the geometric
means of in vitro Ki values were compared with the means of in vivo Ki values
(Ki,u,plasma) which were calculated as Cu,plasma values at 50% occupancy of SERT
obtained from previous clinical positron emission tomography/single photon
emission computed tomography imaging studies for 6 selective serotonin
transporter reuptake inhibitors and 3 serotonin norepinephrine reuptake
inhibitors. The in vitro Ki values for 7 drugs were comparable to their in vivo
Ki,u,plasma values within 3-fold difference. SERT occupancy was overestimated for
5 drugs (P-glycoprotein substrates) and underestimated for 2 drugs (presumably
uptake transporter substrates, although no evidence exists as yet). In
conclusion, prediction of human SERT occupancy from in vitro Ki values and
Cu,plasma was successful for drugs that are not transporter substrates and will
become possible in future even for transporter substrates, once the transporter
activities will be accurately estimated from in vitro experiments.
PMID- 28501471
TI - Comparison of endoscopic ultrasound guided fine needle aspiration and PET/CT in
preoperative diagnosis of pancreatic adenocarcinoma.
AB - BACKGROUND: Endoscopic ultrasound guided fine needle aspiration (EUS-FNA) is the
procedure of choice to investigate and sample pancreatic masses for the
preoperative diagnosis of pancreatic ductal adenocarcinoma (PDAC). The role of
18fluoro-deoxyglucose positron emission tomography/computed tomography (PET/CT)
in PDAC is debated. This study evaluates the role of EUS-FNA as compared to
PET/CT in the preoperative evaluation of PDAC. METHODS: Preoperative evaluation
by PET/CT and EUS-FNA was performed on 25 patients with pancreatic solid lesions,
who underwent a subsequent Whipple procedure or partial pancreatic resection.
RESULTS: This series included 19 PDACs and 6 non-PDACs including 1 metastatic
breast ductal adenocarcinoma, 2 low grade neuroendocrine tumors, 2 chronic
pancreatitis and 1 gastrointestinal tumor abutting the pancreas. EUS-FNA
correctly diagnosed 18 of 19 PDACs, 1 metastatic breast ductal adenocarcinoma and
all 5 of the other non-PDAC cases. One case of well differentiated PDAC was
negative on EUS-FNA. PET/CT provided excellent size and was positive in 14 of 19
PDACs and the metastatic breast ductal adenocarcinoma. The sensitivity,
specificity, positive predictive value, negative predictive value and accuracy
for EUS-FNA in diagnosis of selected pancreatic tumors were 91%, 100%, 100%, 50%
and 92%, respectively, while they were 65%, 100%, 100%, 20% and 68% for PET/CT,
respectively. CONCLUSIONS: Compared to PET/CT, EUS-FNA has a higher sensitivity
and accuracy for preoperative diagnosis of PDAC. However, PET/CT provides
excellent size, volume and stage information. A combination of both PET/CT and
EUS will better help guide diagnosis and treatment of pancreatic adenocarcinoma.
PMID- 28501473
TI - Electrical status epilepticus during sleep in Mowat-Wilson syndrome.
AB - AIM: Mowat-Wilson Syndrome (MWS) is a genetic rare disease. Epilepsy is present
in 70-75% of Patients and an age-dependent electroclinical pattern has been
described. Up to date, there are studies with overnight sleep EEGs, probably
because of the severe intellectual disability (ID) and hyperactivity of these
Patients. Our purpose was to verify the hypothesis that MWS Patients might have
electrical status epilepticus in slow wave sleep (ESES pattern). METHODS: A
retrospective analysis of anamnestic and electrographic data was performed on 7
consecutive MWS Patients followed between 2007 and 2016. Only Patients with at
least one overnight sleep EEG were included in the study. RESULTS: Five out of 7
Patients had overnight sleep EEG studies and were included in this study. All of
them had an anterior ESES pattern with spike-and-wave index>85%. The architecture
of sleep was abnormal. An ESES related regression of cognitive and motor
functions with impact on daily activities (ESES-related syndrome) was
demonstrated in 3 out of 5 (60%) Patients. In two Patients marked improvement of
cognitive and motor performances was observed when the epileptiform activity
during sleep was successfully controlled or it was spontaneously reduced.
CONCLUSIONS: The clinical significance of the ESES pattern is hard to assess in
MWS Patients due to severe ID, but changing in behaviour or in motor and
cognitive functions should mandate sleep EEG investigation and, if ESES is
present, an appropriate treatment should be tried. Furthermore, overnight sleep
EEG recordings, if regularly performed in the follow up, might help to understand
if ESES pattern hampers the cognitive and communicative profile in MWS.
PMID- 28501472
TI - Prokaryotic expression of a codon-optimized capsid gene from duck circovirus and
its application to an indirect ELISA.
AB - Duck circovirus (DuCV), as a causative agent of long-term immunosuppressive
disease, has caused heavy damage to waterfowl breeding worldwide. In this study,
the full-length Cap (capsid) gene of DuCV was expressed in Escherichia coli (E.
coli) for the first time by optimizing the codons in its nuclear localization
signal (NLS) regions. The recombinant protein was expressed as inclusion bodies,
and the quantification of purified Cap protein could reach 0.29mgmL-1. Moreover,
an indirect ELISA method (Cap-ELISA) was established based on the recombinant Cap
protein. The results of the optimization for Cap-ELISA revealed that the optimum
concentration of the coating antigen and serum dilution ratio were 19.5ng per
well and 1:1280, respectively. The cut-off value of the Cap-ELISA for positive
sample detection was 0.145, the sensitivity of that reached 1:25600, and it was
specific for the detection of DuCV anti-sera. In comparative experiments using 56
clinically suspected DuCV-infection samples, the Cap-ELISA showed a 94.64%
coincidence rate with the PCR test. These results indicated that codon
optimization is a reasonable strategy to obtain an intact Cap protein, and this
Cap-ELISA is suitable for extensive applications in DuCV serological diagnosis.
PMID- 28501474
TI - A case of mumps-related acute encephalopathy with biphasic seizures and late
reduced diffusion.
AB - BACKGROUND: Mumps is a common childhood viral disease characterized by fever and
swelling of the parotid gland. The prognosis is generally good, although some
complications, such as encephalitis (0.1%), exist. Acute encephalopathy with
biphasic seizures and late reduced diffusion is the most common type of acute
encephalopathy. However, this type of encephalopathy has not been reported in
association with mumps infection. PATIENT: A previously healthy 3-year-old
Japanese boy had a brief convulsion after fever for 3days, and then had conscious
disturbance and parotitis. After several days, he had a second brief convulsion
and was admitted. Increased serum amylase levels and presence of anti-mumps
immunoglobulin M antibody confirmed mumps parotitis. The patient had another
brief seizure later the day of admission. He did not have status or cluster
seizures, although the biphasic nature of his seizures, conscious disturbance
between the seizures, no pleocytosis in cerebrospinal fluid, and brain magnetic
resonance images were consistent with acute encephalopathy with biphasic seizures
and late reduced diffusion. DISCUSSION: In Japan, the mumps vaccine is not
administered as a part of routine immunizations. It thus has low coverage (30
40%), and as a result, mumps infections are still common. However, this is the
first case of mumps-related acute encephalopathy with biphasic seizures and late
reduced diffusion. This case may be representative of only a minority of patients
with mumps-associated central nervous system involvement. Nevertheless, this
diagnostic possibility may be considered. In order to prevent mumps-related
complications, routine mumps vaccination might be warranted.
PMID- 28501475
TI - Long term kinetic measurements revealing precision and general performance of
surface plasmon resonance biosensors.
AB - This work presents an extensive parameter list that facilitates a survey of
biosensor performance using Biacore instruments for kinetic binding studies. Six
long term measurements were performed using a strongly interacting antigen
antibody (beta2 microglobulin) system. Both Single Cycle Kinetic (SCK) and Multi
Cycle Kinetic (MCK) were executed each with five different analyte
concentrations. The overall comparison of the long term monitored parameters,
like the dissociation constant (KD with approximately 3-6% relative percental
standard deviation), the association and dissociation rate constants (ka, kd),
the analyte binding capacity (Rmax), chi2 and the sum of the absolute values of
the residuals, revealed the delicate factors that make the system performance
vulnerable. The main influential factors on kinetic performance were the
regeneration conditions, the quality of the sensor surface, the usage time and
alteration of the sensor surface, the dilution series and the number of run
cycles (about 250-600 per chip). Moreover the direct comparison of MCK and SCK
uncovered distinct differences in the accuracy of the KD values. The study of
sensor chips from two manufacturers showed distinct differences in the precision
of the data. Using control charts for the surveillance of these parameters
contributes to an overall better system performance.
PMID- 28501477
TI - Co-accumulation of cis-regulatory and coding mutations during the
pseudogenization of the Xenopus laevis homoeologs six6.L and six6.S.
AB - Common models for the evolution of duplicated genes after genome duplication are
subfunctionalization, neofunctionalization, and pseudogenization. Although the
crucial roles of cis-regulatory mutations in subfunctionalization are well
documented, their involvement in pseudogenization and/or neofunctionalization
remains unclear. We addressed this issue by investigating the evolution of
duplicated homeobox genes, six6.L and six6.S, in the allotetraploid frog Xenopus
laevis. Based on a comparative expression analysis, we observed similar eye
specific expression patterns for the two loci and their single ortholog in the
ancestral-type diploid species Xenopus tropicalis. However, we detected lower
levels of six6.S expression than six6.L expression. The six6.S enhancer sequence
was more highly diverged from the orthologous enhancer of X. tropicalis than the
six6.L enhancer, and showed weaker activity in a transgenic reporter assay. Based
on a phylogenetic analysis of the protein sequences, we observed greater
divergence between X. tropicalis Six6 and Six6.S than between X. tropicalis Six6
and Six6.L, and the observed mutations were reminiscent of a microphthalmia
mutation in human SIX6. Misexpression experiments showed that six6.S has weaker
eye-enlarging activity than six6.L, and targeted disruption of six6.L reduced the
eye size more significantly than that of six6.S. These results suggest that
enhancer attenuation stimulates the accumulation of hypomorphic coding mutations,
or vice versa, in one duplicated gene copy and facilitates pseudogenization. We
also underscore the value of the allotetraploid genome of X. laevis as a resource
for studying latent pathogenic mutations.
PMID- 28501476
TI - Endothelial cells are not required for specification of respiratory progenitors.
AB - Crosstalk between mesenchymal and epithelial cells influences organogenesis in
multiple tissues, such as lung, pancreas, liver, and the nervous system. Lung
mesenchyme comprises multiple cell types, however, and precise identification of
the mesenchymal cell type(s) that drives early events in lung development remains
unknown. Endothelial cells have been shown to be required for some aspects of
lung epithelial patterning, lung stem cell differentiation, and regeneration
after injury. Furthermore, endothelial cells are involved in early liver and
pancreas development. From these observations we hypothesized that endothelial
cells might also be required for early specification of the respiratory field and
subsequent lung bud initiation. We first blocked VEGF signaling in E8.5 cultured
foreguts with small molecule VEGFR inhibitors and found that lung specification
and bud formation were unaltered. However, when we examined E9.5 mouse embryos
carrying a mutation in the VEGFR Flk-1, which do not develop endothelial cells,
we found that respiratory progenitor specification was impeded. Because the E9.5
embryos were substantially smaller than control littermates, suggesting the
possibility of developmental delay, we isolated and cultured foreguts from mutant
and control embryos on E8.5, when no size differences were apparent. We found
that both specification of the respiratory field and lung bud formation occurred
in mutant and control explants. These observations were unaffected by the
presence or absence of serum. We also observed that hepatic specification and
initiation occurred in the absence of endothelial cells, and that expansion of
the liver epithelium in culture did not differ between mutant and control
explants. Consistent with previously published results, we also found that
pancreatic buds were not maintained in cultured foreguts when endothelial cells
were absent. Our observations support the conclusion that endothelial cells are
not required for early specification of lung progenitors and bud initiation, and
that the diminished lung specification seen in E9.5 Flk-/- embryos is likely due
to developmental delay resulting from the insufficient delivery of oxygen,
nutrients, and other factors in the absence of a vasculature.
PMID- 28501479
TI - Risk factors for complex regional pain syndrome in patients with surgically
treated traumatic injuries attending hand therapy.
AB - STUDY DESIGN: Prospective cohort study. INTRODUCTION: Identification of risk
factors for CRPS development in patients with surgically treated traumatic
injuries attending hand therapy allows to watch at-risk patients more closely for
early diagnosis and to take precautionary measures as required. PURPOSE OF THE
STUDY: The aim of this study was to evaluate the risk factors for the development
of complex regional pain syndrome (CRPS) after surgical treatment of traumatic
hand injuries. METHODS: In this prospective cohort, 291 patients with traumatic
hand injuries were evaluated 3 days after surgery and monitored for 3 months for
the development of CRPS. The factors assessed for the development of CRPS were
age, sex, manual work, postoperative pain within 3 days measured on a Pain
Numerical Rating Scale (0-10), and injury type (crush injury, blunt trauma, and
cut laceration injury). RESULTS: CRPS was diagnosed in 68 patients (26.2 %) with
a duration of 40.10 +/- 17.01 days between the surgery and CRPS diagnosis. The
mean postoperative pain score was greater in patients with CRPS than in those
without CRPS (P < .001). Patients with pain scores >= 5 had a high risk of
developing CRPS compared with patients with pain scores <5 (odds ratio: 3.61,
confidence interval = 1.94-6.70). Patients with crush injuries were more likely
to develop CRPS (odds ratio: 4.74, confidence interval = 2.29-9.80). CONCLUSIONS:
The patients with a pain score of >=5 in the first 3 days after surgery and the
patients with crush injury were at high risk for CRPS development after surgical
treatment of traumatic hand injuries. LEVEL OF EVIDENCE: II b.
PMID- 28501478
TI - Osr1 functions downstream of Hedgehog pathway to regulate foregut development.
AB - During early fetal development, paracrine Hedgehog (HH) ligands secreted from the
foregut epithelium activate Gli transcription factors in the surrounding
mesenchyme to coordinate formation of the respiratory system, digestive track and
the cardiovascular network. Although disruptions to this process can lead to
devastating congenital defects, the underlying mechanisms and downstream targets,
are poorly understood. We show that the zinc finger transcription factor Osr1 is
a novel HH target as Osr1 expression in the foregut mesenchyme depends on HH
signaling and the effector of HH pathway Gli3 binds to a conserved genomic loci
near Osr1 promoter region. Molecular analysis of mouse germline Osr1 mutants
reveals multiple functions of Osr1 during foregut development. Osr1 mutants
exhibit fewer lung progenitors in the ventral foregut. Osr is then required for
the proper branching of the primary lung buds, with mutants exhibiting miss
located lung lobes. Finally, Osr1 is essential for proper mesenchymal
differentiation including pulmonary arteries, esophageal and tracheal smooth
muscle as well as tracheal cartilage rings. Tissue specific conditional knockouts
in combination with lineage tracing indicate that Osr1 is required cell
autonomously in the foregut mesenchyme. We conclude that Osr1 is a novel
downstream target of HH pathway, required for lung specification, branching
morphogenesis and foregut mesenchymal differentiation.
PMID- 28501480
TI - Assessing manual dexterity: Comparing the WorkAbility Rate of Manipulation Test
with the Minnesota Manual Dexterity Test.
AB - STUDY DESIGN: Cross-sectional study. INTRODUCTION: The WorkAbility Rate of
Manipulation Test (WRMT), an adaptation of the Minnesota Manual Dexterity Test
(MMDT), contains a revised board and protocols to improve its utility for therapy
or fitness assessment. PURPOSE OF THE STUDY: To describe the development and
preliminary psychometric properties of WRMT. METHODS: Sixty-six healthy
participants completed MMDT and WRMT in a random order followed by a user
experience survey. We compared tests using repeated-measures analysis of
variance, test-retest reliability, and examined agreement between tests. RESULTS:
Despite the similarities of these 2 instruments, the different administration
protocols resulted in statistically different score distributions (P < .001).
Results supported good test-retest reliability of WRMT (placing test ICC = 0.88
0.90 and turning test ICC = 0.68-0.82). The WRMT correlated moderately with MMDT
(r = 0.81 in placing test and r = 0.44-0.57 in turning test). Bland-Altman plot
showed that the differences in completion time were 3.8 seconds between placing
tests and 19.6 (both hands), 0.3 (right hand), and 3.9 (left hand) seconds
between turning tests. Overall, participants felt that the instruction of WRMT
was easier to follow (44%) and preferred its setup, color, and depth of the test
board (49%). Time required to complete 1 panel of 20 disks correlated highly with
the time needed to finish a complete trial of 60 disks in both MMDT (r = 0.91
0.97) and WRMT (r = 0.88-0.95). CONCLUSIONS: Caution is warranted in comparing
scores from these 2 test variants. LEVEL OF EVIDENCE: 3b.
PMID- 28501481
TI - Effect of Lymphadenectomy During Radical Nephroureterectomy in Locally Advanced
Upper Tract Urothelial Carcinoma.
AB - BACKGROUND: The role of lymph node dissection (LND) for upper tract urothelial
carcinoma (UTUC) patients remains controversial. The aim of this study was to
evaluate the effect of LND on clinical outcomes during radical nephroureterectomy
(RNU) and to determine prognostic factors of survival. PATIENTS AND METHODS: From
1985 to 2013, 404 patients with UTUC underwent RNU; 5 patients who received
neoadjuvant chemotherapy were excluded. Among them, 182 (46%) were pathologically
negative for lymph node metastasis (pN0), 177 (44%) were non-LND (pNx), and 40
(10%) were positive for lymph nodes metastasis (pN1/2). RESULTS: The 5-year
disease-free survival (DFS) and cancer-specific survival (CSS) rate were higher
in pN0 patients than in pNx patients and in pN1/2 patients. According to
multivariate analysis, non-LND was an independent predictive factor of DFS
(hazard ratio [HR], 1.91; P = .004) and CSS (HR, 2.28; P = .003). In the subgroup
with muscle-invasive UTUC, the 5-year DFS and CSS rates were higher in pN0
patients than in pNx patients. However, there was no statistical difference
between pN0 and pNx groups in terms of DFS and CSS in the pT2 cases. DFS and CSS
times were significantly prolonged in the pN0 group in the locally advanced UTUC
patients (>=pT3). CONCLUSION: In the >=pT3 subgroup, the 5-year DFS and CSS were
significantly prolonged in the pN0 group, but there were no statistical
differences between pN0 and pNx groups in terms of DFS and CSS in the pT2
subgroup. LND for patients with locally advanced UTUC might improve disease
prognosis.
PMID- 28501482
TI - Ciproxifan improves cholinergic transmission, attenuates neuroinflammation and
oxidative stress but does not reduce amyloid level in transgenic mice.
AB - AIM: The present study is aimed to investigate the ability of ciproxifan, a
histamine H3 receptor antagonist to inhibit beta-amyloid (Abeta)-induced
neurotoxicity in SK-N-SH cells and APP transgenic mouse model. MATERIALS AND
METHODS: In vitro studies was designed to evaluate the neuroprotective effects of
ciproxifan in Abeta25-35 - induced SK-N-SH cells. For the in vivo study,
ciproxifan (1 and 3mg/kg, i.p.) was administrated to transgenic mice for 15days
and behaviour was assessed using the radial arm maze (RAM). Brain tissues were
collected to measure Abeta levels (Abeta1-40 and Abeta1-42), acetylcholine (ACh),
acetylcholinesterase (AChE), nitric oxide (NO), lipid peroxidation (LPO),
antioxidant activities, cyclooxygenases (COX) and cytokines (IL-1alpha, IL-1beta
and IL-6), while plasma was collected to measure TGF-1beta. RESULTS: The in vitro
studies demonstrated neuroprotective effect of ciproxifan by increasing cell
viability and inhibiting reactive oxygen species (ROS) in Abeta25-35-induced SK-N
SH cells. Ciproxifan significantly improved the behavioural parameters in RAM.
Ciproxifan however, did not alter the Abeta levels in APP transgenic mice.
Ciproxifan increased ACh and showed anti-oxidant properties by reducing NO and
LPO levels as well as enhancing antioxidant levels. The neuroinflammatory
analysis showed that ciproxifan reduced both COX-1 and COX-2 activities,
decreased the level of pro-inflammatory cytokines IL-1alpha, IL-1beta and IL-6
and increased the level of anti-inflammatory cytokine TGF-1beta. CONCLUSION: This
present study provides scientific evidence of the use of ciproxifan via
antioxidant and cholinergic pathways in the management of AD.
PMID- 28501484
TI - Response to Letter to the Editor.
PMID- 28501483
TI - Reversal of bioenergetics dysfunction by diphenyl diselenide is critical to
protection against the acetaminophen-induced acute liver failure.
AB - Physiopathological conditions such as acute liver failure (ALF) induced by
acetaminophen (APAP) can often impair the mitochondrial bioenergetics. Diphenyl
diselenide [(PhSe)2] has been shown protects against APAP-induced ALF. The
present study aimed to clarify the signaling mechanism involved in the protection
of bioenergetics dysfunction associated with ALF-induced by APAP overdose. Mice
received APAP (600mg/kg) or (PhSe)2 (15.6mg/kg) alone, or APAP+(PhSe)2, all the
solutions were administered by the intraperitoneal (i.p.). Samples of liver,
blood and liver mitochondria were collected at 2 and 4h after APAP
administration. APAP-induced ALF was able to induce ALF by means of alteration on
liver injury biomarkers, increased Nitrite and Nitrate levels and the impairment
of oxidative phosphorylation capacity (OXPHOS). In parallel, APAP overdose
promoted activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and
Heat shock protein 70 (HSP70) expression. (PhSe)2 was able to abolish the APAP
induced decline of OXPHOS and changes on the Nrf2-ARE pathway. In addition,
(PhSe)2 elevated the levels of peroxisome proliferator-activated receptor-gamma
coactivator (PGC-1alpha), helping to restore the levels of nuclear respiratory
factor 1 (NRF1) associated with mitochondrial biogenesis. In summary, the
treatment with (PhSe)2 maintained mitochondrial function, promoted genes related
to mitochondrial dynamic and demonstrating to play critical role in the
modulation of cellular protective responses during ALF.
PMID- 28501486
TI - Food additives: A special issue of the journal Food and Chemical Toxicology.
PMID- 28501485
TI - Rapid genotyping of Legionella pneumophila serogroup 1 strains by a novel DNA
microarray-based assay during the outbreak investigation in Warstein, Germany
2013.
AB - Between 1 August and 6 September 2013, an outbreak of Legionnaires' disease (LD)
with 78 cases confirmed by positive urinary antigen tests occurred in Warstein,
North Rhine-Westphalia, Germany. Legionella (L.) pneumophila, serogroup (Sg) 1,
monoclonal antibody (mAb) subgroup Knoxville, sequence type (ST) 345, was
identified as the epidemic strain. This strain was isolated from seven patients.
To detect the source of the infection, epidemiological typing of clinical and
environmental strains was performed in two consecutive steps. First, strains were
typed by monoclonal antibodies. Indistinguishable strains were further subtyped
by sequence-based typing (SBT) which is the internationally recognized standard
method for epidemiological genotyping of L. pneumophila. In an early stage of the
outbreak investigation, many environmental isolates were found to belong to the
mAb subgroup Knoxville, but to two different STs, namely to ST 345, the epidemic
strain, and to ST 600. A majority of environmental isolates belonged to ST 600
whereas the epidemic ST 345 strain was less common in environmental samples. To
rapidly distinguish both Knoxville strains, we applied a novel typing method
based on DNA-hybridization on glass chips. The new assay can easily and rapidly
discriminate L. pneumophila Sg 1 strains. Thus, we were able to quickly identify
the sources harboring the epidemic strain, i.e., two cooling towers of different
companies, the waste water treatment plants (WWTP) of the city and one company as
well as water samples of the river Wester and its branches.
PMID- 28501487
TI - Inhibition on cholinesterase and tyrosinase by alkaloids and phenolics from
Aristotelia chilensis leaves.
AB - It is reported in this study the effect of isolates from leaves of Aristotelia
chilensis as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase
(BChE) and tyrosinase enzymes. The aim of the paper was to evaluate the activity
of A. chilensis towards different enzymes. In addition to pure compounds,
extracts rich in alkaloids and phenolics were tested. The most active F5
inhibited AChE (79.5% and 89.8% at 10.0 and 20.0 MUg/mL) and against BChE (89.5%
and 97.8% at 10.0 and 20.0 MUg/mL), showing a strong mixed-type inhibition
against AChE and BChE. F3 (a mixture of flavonoids and phenolics acids), showed
IC50 of 90.7 and 59.6 MUg/mL of inhibitory activity against AChE and BChE,
inhibiting the acetylcholinesterase competitively. Additionally, F3 showed and
high potency as tyrosinase inhibitor with IC50 at 8.4 MUg/mL. Sample F4
(anthocyanidins and phenolic composition) presented a complex, mixed-type
inhibition of tyrosinase with a IC50 of 39.8 MUg/mL. The findings in this
investigation show that this natural resource has a strong potential for future
research in the search of new phytotherapeutic treatments for cholinergic
deterioration ailments avoiding the side effects of synthetic drugs. This is the
first report as cholinesterases and tyrosinase inhibitors of alkaloids and
phenolics from A. chilensis leaves.
PMID- 28501488
TI - Laminaria Japonica Polysaccharides effectively inhibited the growth of
nasopharyngeal carcinoma cells in vivo and in vitro study.
AB - AIMS: Laminaria Japonica Polysaccharides (LJP) is a kind of plant polysaccharide
isolated from Laminaria Japonica Aresch. LJP has a variety of biological
activity, including anti-tumor, improving immune function, anti-radiation and
others. This study observed the biological activity of LJP in vitro and in vivo
on human nasopharyngeal carcinoma(NPC), and the possible anticancer mechanism was
explored. METHODS: Nasopharyngeal poorly differentiated squamous cell carcinoma
cell lines CNE2 and HONE1 were used for the study. MTT method was used to detect
the proliferation of HONE1 and CNE2 treated with gradient concentrations of LJP.
The apoptosis of HONE1 treated with LJP was detected by annexin V-FITC/PI double
staining method. HONE1 was used to establish subcutaneous implanted tumor model
in nude mice. The changes of transplanted tumor volume and body weight of nude
mice in each group were observed and recorded. The changes of the ultrastructure
of transplanted tumor were observed by transmission electron microscope (TEM).
RESULTS: MTT results showed that LJP has inhibitory effect on proliferation of
both HONE1 and CNE2, and the effects were dosage-dependent; results of flow
cytometry (FCM) analysis showed that, LJP could efficient induce apoptosis in
HONE1, and apoptosis rate increased with the increase of LJP concentration. In
vivo experiments, the inhibition rate was 33.7% (P<0.05) and 47% (P<0.01) in
middle and high dose LJP group, respectively. TEM results suggested that the
cancer cells in the transplanted tumor tissue treated with middle and high dose
LJP presented unique apoptosis changes. CONCLUSIONS: LJP can effectively inhibit
the growth of NPC cells. And it may be achieved by inducing apoptosis of NPC
cells.
PMID- 28501489
TI - Hydroxyethyl starch 130/0.4 compared with 0.9% NaCl administered to greyhounds
with haemorrhagic shock.
AB - OBJECTIVE: To determine the cardiovascular and acid-base effects of 6%
hydroxyethyl starch (HES) 130/0.4 and 0.9% sodium chloride (NaCl) administered to
anaesthetized greyhounds with haemorrhagic shock. STUDY DESIGN: Prospective,
experimental, complete randomized block design. ANIMALS: Twelve healthy adult
greyhounds. METHODS: After 60 minutes of isoflurane anaesthesia, 48 mL kg-1 of
blood was removed to induce hypotension. Dogs were randomized to receive either
20 mL kg-1 of HES 130/0.4 or 80 mL kg-1 of 0.9% NaCl over 20 minutes.
Haemoglobin, arterial and central venous blood gas and electrolytes, lactate,
mean arterial pressure (MAP) and cardiac index were measured at: T0, 60 minutes
after induction of anaesthesia, immediately prior to blood removal; T1,
immediately after blood removal; T2, immediately after fluid administration; and
T3, 40 minutes after fluid administration. Oxygen extraction ratio (O2ER) was
calculated at each sample time. RESULTS: O2ER increased at T1 and decreased at T2
and T3, with no difference between the two groups. Dogs administered HES 130/0.4
had higher lactate at T2 [mean (95% confidence interval) 1.3 (0.8-1.9) mmol L-1]
than dogs administered 0.9% NaCl [0.8 (0.5-1.1) mmol L-1]; p = 0.045. Dogs
administered HES 130/0.4 had a higher MAP at T3 [88 (74-102) mmHg] than dogs
administered 0.9% NaCl [69 (60-79) mmHg]; p = 0.019. Dogs administered 0.9% NaCl
were more acidaemic at T2 and T3, including higher hydrogen ion, lower
bicarbonate, lower base excess and higher chloride concentrations. CONCLUSION:
and clinical relevance The effect of 20 mL kg-1 of HES 130/0.4 on shock, as
measured by O2ER, was no different than that of 80 mL kg-1 of 0.9% NaCl in dogs
under general anaesthesia. Acidaemia in the NaCl group is likely attributable to
hyperchloraemic metabolic acidosis from the larger volume administered.
PMID- 28501490
TI - Colistin use in critically ill neonates: A case-control study.
AB - BACKGROUND: The aim of this study was to assess the safety and efficacy of
colistin use in critically ill neonates. METHODS: This was a case-control study
that included newborn infants with proven or suspected nosocomial infections
between January 2012 and October 2015, at two centers in Diyarbakir, Turkey. The
clinical and laboratory characteristics and outcomes of patients who received
colistin therapy were reviewed and compared to patients who were treated with
antimicrobial agents other than colistin during the same period. RESULTS: Forty
seven cases who received intravenous colistin (colistin group) and 59 control
patients (control group) were included. There were no significant differences
between the groups regarding outcomes and nephrotoxicity, including acute renal
failure. Colistin therapy was associated with significantly reduced serum
magnesium (1.38 +/- 0.39 mg/dL vs. 1.96 +/- 0.39 mg/dL, p < 0.001) and
hypokalemia (46.8% vs. 25.4%, p = 0.026). The patients who received colistin also
had longer hospital stays (43 (32-70) days vs. 39 (28-55) days, p = 0.047), a
higher rate of previous carbapenem exposure (40.4% vs. 11.9%, p = 0.001), and a
higher age at the onset of infection (13 (10-21) days vs. 11 (9-15) days, p =
0.03). CONCLUSION: This study showed that colistin was both effective and safe
for treating neonatal infections caused by multidrug-resistant gram-negative
bacteria. However, intravenous colistin use was significantly associated with
hypomagnesemia and hypokalemia.
PMID- 28501491
TI - Diagnostic usefulness of Xpert MTB/RIF assay for detection of tuberculous
meningitis using cerebrospinal fluid.
AB - OBJECTIVE: Tuberculous meningitis (TBM) is the most severe form of extra
pulmonary tuberculosis (TB) due to association of diseases with high rates of
mortality and morbidity. Diagnosis continues to be a clinical challenge as
microbiological confirmation is rare and time consuming resulting in delayed
treatment. Xpert MTB/RIF assay is a rapid and simple test, which has been
endorsed by World Health Organization as an initial diagnostic test for the
diagnosis of TBM. However, evidence still lacks for its performance on
cerebrospinal fluid (CSF) for the diagnosis of TBM especially from India.
METHODS: A total of 267 CSF samples from patients with high clinico-radiological
suspicion of TBM were included in this study. Ziehl-Neelsen (ZN) staining, BACTEC
Mycobacterial Growth Indicator Tube (MGIT-960) culture system, and Xpert MTB/RIF
assay (using cartridge version G4) were tested on all samples. RESULTS: Of total
267 samples, all were negative for smear AFB and 52 (19.5%) were culture positive
by MGIT-960 culture system. However, out of 52 (19.5%) cultures detected positive
by MGIT-960, 5 (9.6%) were detected as resistant to rifampicin. Xpert MTB/RIF
assay was positive in 38 (14.2%) samples and negative in 223 (83.5%) samples.
Cartridge error was detected in 6 (2.2%) samples, which could not be repeated due
to insufficient sample volume. The sensitivity and specificity of Xpert MTB/RIF
assay in comparison to MGIT-960 was 55.1% (95%, CI: 40.2-69.3) and 94.8% (95%,
CI: 90.9-97.4) respectively. Overall, Xpert MTB/RIF assay detected 38 (14.2%) as
positive for MTB of which 4 (10.5%), 31 (81.6%) and 3 (7.9%) were found to be
rifampicin resistant, sensitive and indeterminate respectively. CONCLUSION: Xpert
MTB/RIF assay showed lower sensitivity as compared to MGIT 960 culture for the
diagnosis of TBM from CSF samples.
PMID- 28501492
TI - LDH inhibition impacts on heat shock response and induces senescence of
hepatocellular carcinoma cells.
AB - In normal cells, heat shock response (HSR) is rapidly induced in response to a
variety of harmful conditions and represents one of the most efficient defense
mechanism. In cancer tissues, constitutive activation converts HSR into a life
threatening process, which plays a major role in helping cell survival and
proliferation. Overexpression of heat shock proteins (HSPs) has been widely
reported in human cancers and was found to correlate with tumor progression.
Hepatocellular carcinoma is one of the conditions in which HSR activation was
shown to have the highest clinical significance. Transcription of HSPs is induced
by HSF-1, which also activates glycolytic metabolism and increases the expression
of LDH-A, the master regulator of the Warburg effect. In this paper, we tried to
explore the relationship between HSR and LDH-A. In cultured hepatocellular
carcinoma cells, by using two enzyme inhibitors (oxamate and galloflavin), we
found that the reduction of LDH-A activity led to decreased level and function of
the major HSPs involved in tumorigenesis. Galloflavin (a polyphenol) also
inhibited the ATPase activity of two of the examined HSPs. Finally, hindering HSR
markedly lowered the alpha-fetoprotein cellular levels and induced senescence.
Specific inhibitors of single HSPs are currently under evaluation in different
neoplastic diseases. However, one of the effects usually observed during
treatment is a compensatory elevation of other HSPs, which decreases treatment
efficacy. Our results highlight a connection between LDH and HSR and suggest LDH
inhibition as a way to globally impact on this tumor promoting process.
PMID- 28501493
TI - Prophylactic warfarin post anterior ST-elevation myocardial infarction: A
systematic review and meta-analysis.
AB - OBJECTIVES: To determine the role of warfarin (WF) prophylaxis in the prevention
of left ventricular thrombus (LVT) formation and subsequent embolic complications
following an anterior ST elevation myocardial infarction (STEMI) complicated by
reduced left ventricular ejection fraction (LVEF) and wall motion abnormalities.
BACKGROUND: The role of oral anticoagulation prophylaxis, in addition to dual
antiplatelet therapy (DAPT), in the current era of percutaneous coronary
intervention has not been well studied, despite being a class IIb recommendation
in the AHA/ACC STEMI guidelines. METHODS: The Cochrane search strategy was used
to search PubMed, Embase and the Cochrane library for relevant results. Four
studies, two retrospective, one prospective registry, and a randomized
feasibility control trial met criteria for inclusion. Data was pooled using a
random effects model and reported as odds ratios (OR) with their 95% confidence
intervals (CI). Primary outcomes of interest were rate of stroke, major bleeding
and mortality. RESULTS: Pooled analysis included 526 patients in the No WF group
and 347 patients in the WF group. No statistical difference in rate of stroke
(OR: 2.72 [95% CI: 0.47-15.88; p=0.21]) or mortality (OR: 1.50 [95% CI 0.29-7.71;
p=0.63]) was observed. Major bleeding was significantly higher in the WF group
(OR: 2.56 [95% CI: 1.34-4.89; p=0.004]). CONCLUSIONS: The routine use of DAPT and
WF for prophylaxis against LVT formation following an anterior STEMI with
associated decrease in LVEF and wall motion abnormalities, appears to result in
no mortality benefit or reduction in stroke rates, but may increase the frequency
of major bleeding.
PMID- 28501494
TI - Focused microwave irradiation-assisted immunohistochemistry to study effects of
ketamine on phospho-ERK expression in the mouse brain.
AB - Ketamine produces rapid and long-lasting antidepressant effects in depressive
patients. Preclinical studies demonstrate that ketamine stimulates AMPA receptor
transmission and activates BDNF/TrkB-Akt/ERK-mTOR signaling cascades, leading to
a sustained increase in synaptic protein synthesis and strengthening of synaptic
plasticity, a potential mechanism underlying the antidepressant effects. The
purpose of this study was to develop an immunohistochemistry (IHC) assay to map
the distribution of extracellular signal-regulated kinase (ERK) phosphorylation
in the mouse brain in response to systemic ketamine treatment. We established a
focused microwave irradiation-assisted IHC assay to detect phosphorylated
(phospho) proteins including phospho-ERK, phospho- cAMP-response- element-binding
protein (CREB), phospho- glutamate receptor 1 (GluR1) and phospho-
calcium/calmodulin-dependent protein kinase II (CaMKII) with greater sensitivity
and reproducibility in comparison to conventional IHC methods. A single dose of
ketamine produced a robust, dose- and time-dependent increase in phospho-ERK
immunoreactive (phospho-ERK-ir) neurons in the medial prefrontal cortex (mPFC)
and the central nucleus of the amygdala. Phospho-ERK-ir neurons in the mPFC were
primarily located in the prelimbic and anterior cingulate subregions with the
morphology resembling pyramidal neurons. An increase in phospho-ERK-ir was also
observed in the brainstem dorsal raphe nucleus and locus coeruleus. The NMDA
GluN2B subtype receptor antagonist Ro 25-6981 increased phospho-ERK expression in
the brain in a similar pattern as ketamine. In summary, we have established a
sensitive and reliable focused microwave irradiation-assisted IHC assay, and
defined the activation pattern of ERK, in response to systemic ketamine and Ro 25
6981 treatment, in brain regions that are potentially responsible for mediating
the antidepressant effects.
PMID- 28501496
TI - Improved life expectancy of people living with HIV: who is left behind?
PMID- 28501495
TI - Survival of HIV-positive patients starting antiretroviral therapy between 1996
and 2013: a collaborative analysis of cohort studies.
AB - BACKGROUND: Health care for people living with HIV has improved substantially in
the past two decades. Robust estimates of how these improvements have affected
prognosis and life expectancy are of utmost importance to patients, clinicians,
and health-care planners. We examined changes in 3 year survival and life
expectancy of patients starting combination antiretroviral therapy (ART) between
1996 and 2013. METHODS: We analysed data from 18 European and North American HIV
1 cohorts. Patients (aged >=16 years) were eligible for this analysis if they had
started ART with three or more drugs between 1996 and 2010 and had at least 3
years of potential follow-up. We estimated adjusted (for age, sex, AIDS, risk
group, CD4 cell count, and HIV-1 RNA at start of ART) all-cause and cause
specific mortality hazard ratios (HRs) for the first year after ART initiation
and the second and third years after ART initiation in four calendar periods
(1996-99, 2000-03 [comparator], 2004-07, 2008-10). We estimated life expectancy
by calendar period of initiation of ART. FINDINGS: 88 504 patients were included
in our analyses, of whom 2106 died during the first year of ART and 2302 died
during the second or third year of ART. Patients starting ART in 2008-10 had
lower all-cause mortality in the first year after ART initiation than did
patients starting ART in 2000-03 (adjusted HR 0.71, 95% CI 0.61-0.83). All-cause
mortality in the second and third years after initiation of ART was also lower in
patients who started ART in 2008-10 than in those who started in 2000-03 (0.57,
0.49-0.67); this decrease was not fully explained by viral load and CD4 cell
count at 1 year. Rates of non-AIDS deaths were lower in patients who started ART
in 2008-10 (vs 2000-03) in the first year (0.48, 0.34-0.67) and second and third
years (0.29, 0.21-0.40) after initiation of ART. Between 1996 and 2010, life
expectancy in 20-year-old patients starting ART increased by about 9 years in
women and 10 years in men. INTERPRETATION: Even in the late ART era, survival
during the first 3 years of ART continues to improve, which probably reflects
transition to less toxic antiretroviral drugs, improved adherence, prophylactic
measures, and management of comorbidity. Prognostic models and life expectancy
estimates should be updated to account for these improvements. FUNDING: UK
Medical Research Council, UK Department for International Development, EU EDCTP2
programme.
PMID- 28501497
TI - The Micro-Managing Fat: Exosomes as a New Messenger.
AB - Brown fat secretes endocrine factors and exerts metabolic effects beyond
thermogenesis. In addition to protein factors and bioactive lipids, recent work
has revealed brown fat-derived miRNAs carried by exosomes as a new means of
interorgan crosstalk, with potentially important implications for metabolic
physiology and disease.
PMID- 28501498
TI - The role of sleep in the plasticity of the olfactory system.
AB - The central olfactory system mediates a variety of odor-guided behaviors crucial
for maintenance of animal life. The olfactory neural circuit must be highly
plastic to ensure that it responds appropriately to changing odor circumstances.
Recent studies have revealed that the processing of odor information changes
drastically during waking and sleep and that neural activity during sleep plays
pivotal roles in the structural reorganization and functional plasticity of the
olfactory system. While olfactory information from the external world is
efficiently transferred to the olfactory cortex (OC) via the olfactory bulb (OB)
during waking, this information flow is attenuated during slow-wave sleep: during
slow-wave sleep, the OC neurons exhibit synchronous discharges without odor input
under the entrainment of sharp waves in the local field potential recording. Top
down transfer of sharp-wave activity to the OB during slow-wave sleep promotes
structural reorganization of the OB neural circuit. Further, the activity of the
OC during sleep is affected by the olfactory experience during prior waking
period, and perturbation of the sleep activity disrupts proper olfactory memory.
Thus, as is seen also in the hippocampus and neocortex, the neural activities of
the olfactory system during sleep likely play essential roles in circuit
reorganization and memory consolidation.
PMID- 28501499
TI - Sleep in vertebrate and invertebrate animals, and insights into the function and
evolution of sleep.
AB - Many mammalian species, including humans, spend a substantial fraction of their
life sleeping. Sleep deprivation in rats ultimately leads to death, indicating
the essential role of sleep. Exactly why sleep is so essential, however, remains
largely unknown. From an evolutionary point of view, almost all animal species
that have been investigated exhibit sleep or sleep-like states, suggesting that
sleep may benefit survival. In certain mammalian and avian species, sleep can be
further divided into at least two stages, rapid eye movement (REM) sleep and non
REM sleep. In addition to a widely conserved role for sleep, these individual
sleep stages may have roles unique to these animals. The recent use of state-of
the-art techniques, including optogenetics and chemogenetics, has greatly
broadened our understanding of the neural mechanisms of sleep regulation,
allowing us to address the function of sleep. Studies focusing on non-mammalian
animals species have also provided novel insights into the evolution of sleep.
This review provides a comprehensive overview regarding the current knowledge of
the function and evolution of sleep.
PMID- 28501500
TI - It's about time: The development and validation of a rapid optimized single
antigen bead (ROB) assay protocol for LABScreen.
AB - The LABScreen single antigen bead assay (SAB) is a method widely used for the
identification and monitoring of human leukocyte antigen (HLA) antibodies in
patients pre-and post-transplant. While accurate testing of patient samples is
key for optimal patient care, time can also be important, especially during
deceased donor workups or post-transplant assessments. Here we describe the
development and validation of the Rapid Optimized SAB (ROB) protocol, a modified
version of the One Lambda LABScreen SAB (OLSAB) procedure, which reduces assay
time from 85 to 25min (>70% reduction) without impacting assay quality or
sensitivity. Optimization steps included shortened centrifugation cycles and
reduced serum and secondary antibody incubation times in combination with
increased secondary antibody concentration. Linear regression analysis of
baseline median fluorescence intensity (MFI) values showed excellent correlation
between the ROB and OLSAB protocols (r2>0.98) for both class I and class II
antibodies in 58 sera tested in two HLA laboratories. Importantly, the ROB
protocol demonstrated a trend towards improved inter-laboratory MFI concordance
when compared to the OLSAB procedure (r2=0.9816 vs 0.9451), especially for HLA
antibody specificities in the 500-2000 MFI range (r2=0.7824 vs 0.6313).
Implementation of the ROB protocol will expedite HLA antibody testing and may
improve reproducibility of the SAB assay.
PMID- 28501501
TI - Anti-tumor effects of differentiation-inducing factor-1 in malignant melanoma:
GSK-3-mediated inhibition of cell proliferation and GSK-3-independent suppression
of cell migration and invasion.
AB - Differentiation-inducing factor-1 (DIF-1) isolated from Dictyostelium discoideum
strongly inhibits the proliferation of various mammalian cells through the
activation of glycogen synthase kinase-3 (GSK-3). To evaluate DIF-1 as a novel
anti-cancer agent for malignant melanoma, we examined whether DIF-1 has anti
proliferative, anti-migratory, and anti-invasive effects on melanoma cells using
in vitro and in vivo systems. DIF-1 reduced the expression levels of cyclin D1
and c-Myc by facilitating their degradation via GSK-3 in mouse (B16BL6) and human
(A2058) malignant melanoma cells, and thereby strongly inhibited their
proliferation. DIF-1 suppressed the canonical Wnt signaling pathway by lowering
the expression levels of transcription factor 7-like 2 and beta-catenin, key
transcription factors in this pathway. DIF-1 also inhibited cell migration and
invasion, reducing the expression of matrix metalloproteinase-2; however, this
effect was not dependent on GSK-3 activity. In a mouse lung tumor formation
model, repeated oral administrations of DIF-1 markedly reduced melanoma colony
formation in the lung. These results suggest that DIF-1 inhibits cell
proliferation by a GSK-3-dependent mechanism and suppresses cell migration and
invasion by a GSK-3-independent mechanism. Therefore, DIF-1 may have a potential
as a novel anti-cancer agent for the treatment of malignant melanoma.
PMID- 28501502
TI - Urtica dioica Extract Inhibits Proliferation and Induces Apoptosis and Related
Gene Expression of Breast Cancer Cells In Vitro and In Vivo.
AB - INTRODUCTION: Currently, because the prevalence of breast cancer and its
consequent mortality has increased enormously in the female population, a number
of studies have been designed to identify natural products with special antitumor
properties. The main purpose of the present study was to determine the effect of
Urtica dioica on triggering apoptosis and diminishing growth, size, and weight of
the tumor in an allograft model of BALB/c mice. MATERIALS AND METHODS: In the
present study, a BALB/c mouse model of breast cancer (4T1) was used. After
emergence of tumor, 2 groups of mice received the extract, 1 group at a dose of
10 mg/kg and 1 group at a dose of 20 mg/kg, by intraperitoneal injection for 28
days. During the test and after removal of the tumor mass, the size and weight of
the tumor were measured. To assess the induction of apoptosis in the cancer
cells, the TUNEL (terminal deoxynucleotidyl transferase deoxyuridine triphosphate
nick-end labeling) assay was performed. The Ki-67 test was used to evaluate tumor
proliferation. RESULTS: The results showed that the tumor size in the mice
treated with the extract decreased significantly. The weight of the tumor mass in
the treated mice after resection was less than that in the control group. The
TUNEL assay findings revealed that apoptosis occurred in the treated group. The
Ki-67 test findings also demonstrated that administration of the extract
suppressed the growth of tumor cells. CONCLUSION: These results suggest that U.
dioica extract can decrease the growth of breast tumors and induce apoptosis in
tumor cells; thus, it might represent an ideal therapeutic tool for breast
cancer.
PMID- 28501504
TI - Transmission of Borrelia miyamotoi sensu lato relapsing fever group spirochetes
in relation to duration of attachment by Ixodes scapularis nymphs.
AB - Borrelia miyamotoi sensu lato relapsing fever group spirochetes are emerging as
causative agents of human illness (Borrelia miyamotoi disease) in the United
States. Host-seeking Ixodes scapularis ticks are naturally infected with these
spirochetes in the eastern United States and experimentally capable of
transmitting B. miyamotoi. However, the duration of time required from tick
attachment to spirochete transmission has yet to be determined. We therefore
conducted a study to assess spirochete transmission by single transovarially
infected I. scapularis nymphs to outbred white mice at three time points post
attachment (24, 48, and 72h) and for a complete feed (>72-96h). Based on
detection of B. miyamotoi DNA from the blood of mice fed on by an infected nymph,
the probability of spirochete transmission increased from 10% by 24h of
attachment (evidence of infection in 3/30 mice) to 31% by 48h (11/35 mice), 63%
by 72h (22/35 mice), and 73% for a complete feed (22/30 mice). We conclude that
(i) single I. scapularis nymphs effectively transmit B. miyamotoi relapsing fever
group spirochetes while feeding, (ii) transmission can occur within the first 24h
of nymphal attachment, and (iii) the probability of transmission increases with
the duration of nymphal attachment.
PMID- 28501503
TI - Detection and molecular characterization of Babesia, Theileria, and Hepatozoon
species in hard ticks collected from Kagoshima, the southern region in Japan.
AB - To reveal the distribution of tick-borne parasites, we established a novel nested
polymerase chain reaction (PCR) system to detect the most common agents of tick
borne parasitic diseases, namely Babesia, Theileria, and Hepatozoon parasites. We
collected host-seeking or animal-feeding ticks in Kagoshima Prefecture, the
southernmost region of Kyusyu Island in southwestern Japan. Twenty of the total
of 776 tick samples displayed a specific band of the appropriate size
(approximately 1.4-1.6kbp) for the 18S rRNA genes in the novel nested PCR
(20/776: 2.58%). These PCR products have individual sequences of Babesia spp.
(from 8 ticks), Theileria spp. (from 9 ticks: one tick sample including at least
two Theileria spp. sequences), and Hepatozoon spp. (from 3 ticks). Phylogenetic
analyses revealed that these sequences were close to those of undescribed Babesia
spp. detected in feral raccoons in Japan (5 sequences; 3 sequences being
identical), Babesia gibsoni-like parasites detected in pigs in China (3
sequences; all sequences being identical), Theileria spp. detected in sika deer
in Japan and China (10 sequences; 2 sequences being identical), Hepatozoon canis
(one sequence), and Hepatozoon spp. detected in Japanese martens in Japan (two
sequences). In summary, we showed that various tick-borne parasites exist in
Kagoshima, the southern region in Japan by using the novel nested PCR system.
These including undescribed species such as Babesia gibsoni-like parasites
previously detected in pigs in China. Importantly, our results revealed new
combinations of ticks and protozoan parasites in southern Japan. The results of
this study will aid in the recognition of potential parasitic animal diseases
caused by tick-borne parasites.
PMID- 28501505
TI - Sevoflurane postconditioning attenuates reactive astrogliosis and glial scar
formation after ischemia-reperfusion brain injury.
AB - Cerebral ischemia leads to astrocyte's activation and glial scar formation. Glial
scar can inhibit axonal regeneration during the recovery phase. It has
demonstrated that sevoflurane has neuroprotective effects against ischemic
stroke, but its effects on ischemia-induced formation of astrogliosis and glial
scar are unknown. This study was designed to investigate the effect of
sevoflurane postconditioning on astrogliosis and glial scar formation in ischemic
stroke model both in vivo and in vitro. The results showed that 2.5% of
sevoflurane postconditioning could significantly reduce infarction volume and
improve neurologic deficits. And it could also decrease the expression of the
glial scar marker glial fibrillary acidic protein (GFAP), neurocan and phosphacan
in the peri-infarct region and markedly reduce the thickness of glial scar after
ischemia/reperfusion (I/R). Consistent with the in vivo data, in the oxygen and
glucose deprivation/reoxygenation (OGD/Re) model, sevoflurane postconditioning
could protect astrocyte against OGD/Re-induced injury, decrease the expression of
GFAP, neurocan and phosphacan. Further studies demonstrated that sevoflurane
postconditioning could down-regulate the expression of Lamp1 and active cathepsin
B, and block I/R or OGD/Re-induced release of cathepsin B from the lysosomes into
cytoplasm. In order to confirm whether inhibition of cathepsin B could attenuate
the formation of glial scar, we used cathepsin B inhibitor CA-074Me as a positive
control. The results showed that inhibition of cathepsin B could decrease the
expression of GFAP, neurocan and phosphacan. Taken together, sevoflurane
postconditioning can attenuate astrogliosis and glial scar formation after
ischemic stroke, associating with inhibition of the activation and release of
lysosomal cathepsin B.
PMID- 28501507
TI - Peering over the chasm: Diffusion of prostate radiation therapy
hypofractionation.
PMID- 28501506
TI - Defective neuronal migration and inhibition of bipolar to multipolar transition
of migrating neural cells by Mesoderm-Specific Transcript, Mest, in the
developing mouse neocortex.
AB - Brain developmental disorders such as lissencephaly can result from faulty
neuronal migration and differentiation during the formation of the mammalian
neocortex. The cerebral cortex is a modular structure, where developmentally,
newborn neurons are generated as a neuro-epithelial sheet and subsequently
differentiate, migrate and organize into their final positions in the cerebral
cortical plate via a process involving both tangential and radial migration. The
specific role of Mest, an imprinted gene, in neuronal migration has not been
previously studied. In this work, we reduced expression of Mest with in utero
electroporation of neuronal progenitors in the developing embryonic mouse
neocortex. Reduction of Mest levels by shRNA significantly reduced the number of
neurons migrating to the cortical plate. Also, Mest-knockdown disrupted the
transition of bipolar neurons into multipolar neurons migrating out of the sub
ventricular zone region. The migrating neurons also adopted a more tangential
migration pattern upon knockdown of the Mest message, losing their potential to
attach to radial glia cells, required for radial migration. The differentiation
and migration properties of neurons via Wnt-Akt signaling were affected by Mest
changes. In addition, miR-335, encoded in a Mest gene intron, was identified as
being responsible for blocking the default tangential migration of the neurons.
Our results suggest that Mest and its intron product, miR-335, play important
roles in neuronal migration with Mest regulating the morphological transition of
primary neurons required in the formation of the mammalian neocortex.
PMID- 28501508
TI - Military metaphors in oncology: Let's not fight about this.
PMID- 28501509
TI - Designer outer membrane vesicles as immunomodulatory systems - Reprogramming
bacteria for vaccine delivery.
AB - Vaccines often require adjuvants to be effective. Traditional adjuvants, like
alum, activate the immune response but in an uncontrolled way. Newer adjuvants
help to direct the immune response in a more coordinated fashion. Here, we review
the opportunity to use the outer membrane vesicles (OMVs) of bacteria as a way to
modulate the immune response toward making more effective vaccines. This review
outlines the different types of OMVs that have been investigated for vaccine
delivery and how they are produced. Because OMVs are derived from bacteria, they
have compositions that may not be compatible with parenteral delivery in humans;
therefore, we also review the strategies brought to bear to detoxify OMVs while
maintaining an adjuvant profile. OMV-based vaccines can be derived from the
pathogens themselves, or can be used as surrogate constructs to mimic a pathogen
through the heterologous expression of specific antigens in a desired host source
strain, and approaches to doing so are reviewed. Additionally, the emerging area
of engineered pathogen-specific carbohydrate sequences, or glycosylated OMVs is
reviewed and contrasted with protein antigen delivery. Existing OMV-based
vaccines as well as their routes of administration round out the text. Overall,
this is an exciting time in the OMV field as it matures and leads to more
effective and targeted ways to induce desired pathogen-specific immune responses.
PMID- 28501511
TI - Identification of quinazoline based inhibitors of IRAK4 for the treatment of
inflammation.
AB - Interleukin-1 receptor associated kinase 4 (IRAK4) has been implicated in IL-1R
and TLR based signaling. Therefore selective inhibition of the kinase activity of
this protein represents an attractive target for the treatment of inflammatory
diseases. Medicinal chemistry optimization of high throughput screening (HTS)
hits with the help of structure based drug design led to the identification of
orally-bioavailable quinazoline based IRAK4 inhibitors with excellent
pharmacokinetic profile and kinase selectivity. These highly selective IRAK4
compounds show activity in vivo via oral dosing in a TLR7 driven model of
inflammation.
PMID- 28501512
TI - Anti-influenza activity of monoterpene-containing substituted coumarins.
AB - Compounds simultaneously carrying the monoterpene and coumarin moieties have been
tested for cytotoxicity and inhibition of activity against influenza virus
A/California/07/09 (H1N1)pdm09. The structure of substituents in the coumarin
framework, as well as the structure and the absolute configuration of the
monoterpenoid moiety, are shown to significantly influence the anti-influenza
activity and cytotoxicity of the compounds under study. The compounds with a
bicyclic pinane framework exhibit the highest selectivity indices (the ratios
between the cytotoxicity and the active dose). The derivative of (-)-myrtenol
15c, which is characterized by promising activity, low cytotoxicity, and
synthetic accessibility, has the greatest potential among this group of
compounds. It exhibited the highest activity when added to the infected cell
culture at early stages of viral reproduction.
PMID- 28501513
TI - QSAR studies of the bioactivity of hepatitis C virus (HCV) NS3/4A protease
inhibitors by multiple linear regression (MLR) and support vector machine (SVM).
AB - In this study, quantitative structure-activity relationship (QSAR) models using
various descriptor sets and training/test set selection methods were explored to
predict the bioactivity of hepatitis C virus (HCV) NS3/4A protease inhibitors by
using a multiple linear regression (MLR) and a support vector machine (SVM)
method. 512 HCV NS3/4A protease inhibitors and their IC50 values which were
determined by the same FRET assay were collected from the reported literature to
build a dataset. All the inhibitors were represented with selected nine global
and 12 2D property-weighted autocorrelation descriptors calculated from the
program CORINA Symphony. The dataset was divided into a training set and a test
set by a random and a Kohonen's self-organizing map (SOM) method. The correlation
coefficients (r2) of training sets and test sets were 0.75 and 0.72 for the best
MLR model, 0.87 and 0.85 for the best SVM model, respectively. In addition, a
series of sub-dataset models were also developed. The performances of all the
best sub-dataset models were better than those of the whole dataset models. We
believe that the combination of the best sub- and whole dataset SVM models can be
used as reliable lead designing tools for new NS3/4A protease inhibitors
scaffolds in a drug discovery pipeline.
PMID- 28501510
TI - Surface engineering for lymphocyte programming.
AB - The once nascent field of immunoengineering has recently blossomed to include
approaches to deliver and present biomolecules to program diverse populations of
lymphocytes to fight disease. Building upon improved understanding of the
molecular and physical mechanics of lymphocyte activation, varied strategies for
engineering surfaces to activate and deactivate T-Cells, B-Cells and natural
killer cells are in preclinical and clinical development. Surfaces have been
engineered at the molecular level in terms of the presence of specific biological
factors, their arrangement on a surface, and their diffusivity to elicit specific
lymphocyte fates. In addition, the physical and mechanical characteristics of the
surface including shape, anisotropy, and rigidity of particles for lymphocyte
activation have been fine-tuned. Utilizing these strategies, acellular systems
have been engineered for the expansion of T-Cells and natural killer cells to
clinically relevant levels for cancer therapies as well as engineered to program
B-Cells to better combat infectious diseases.
PMID- 28501514
TI - Stabilizing HDAC11 with SAHA to assay slow-binding benzamide inhibitors.
AB - Among 18 human histone deacetylases (HDAC), HDAC11 is least studied. MS275, a
benzamide HDAC inhibitor (HDACi), was stereotypically considered to selectively
target Class I HDACs. We verified this slow-binding inhibitor also targeted
HDAC11. In a traditional enzyme based assay, MS275 at low concentrations
surprisingly behaved as an agonist. This was attributed to the poor stability of
HDAC11 which lost 40% activity in 3h at 37 degrees C. By adding 0.2MUM SAHA,
HDAC11 activity was stabilized during the 3-h assay period. Since 0.2MUM SAHA
inhibited 50% HDAC11 activity, the apparent IC50' of MS275 was adjusted to the
true IC50=0.65MUM. Finally, the new method demonstrated its superiority in one
dose-screening assays by decreasing false negative results. This work highlighted
an optimized strategy to assay slow-binding inhibitors of unstable proteins with
known fast-binding inhibitors. It should be especially useful in a hit-discovery
stage to find moderate potent compounds.
PMID- 28501515
TI - Shrimp humoral responses against pathogens: antimicrobial peptides and
melanization.
AB - Diseases have caused tremendous economic losses and become the major problem
threatening the sustainable development of shrimp aquaculture. The knowledge of
host defense mechanisms against invading pathogens is essential for the
implementation of efficient strategies to prevent disease outbreaks. Like other
invertebrates, shrimp rely on the innate immune system to defend themselves
against a range of microbes by recognizing and destroying them through cellular
and humoral immune responses. Detection of microbial pathogens triggers the
signal transduction pathways including the NF-kappaB signaling, Toll and Imd
pathways, resulting in the activation of genes involved in host defense
responses. In this review, we update the discovery of components of the Toll and
Imd pathways in shrimp and their participation in the regulation of shrimp
antimicrobial peptide (AMP) synthesis. We also focus on a recent progress on the
two most powerful and the best-studied shrimp humoral responses: AMPs and
melanization. Shrimp AMPs are mainly cationic peptides with sequence diversity
which endues them the broad range of activities against microorganisms.
Melanization, regulated by the prophenoloxidase activating cascade, also plays a
crucial role in killing and sequestration of invading pathogens. The progress and
emerging research on mechanisms and functional characterization of components of
these two indispensable humoral responses in shrimp immunity are summarized and
discussed. Interestingly, the pattern recognition protein (PRP) crosstalk is
evidenced between the proPO activating cascade and the AMP synthesis pathways in
shrimp, which enables the innate immune system to build up efficient immune
responses.
PMID- 28501516
TI - Is dual inhibition of metalloenzymes HDAC-8 and MMP-2 a potential pharmacological
target to combat hematological malignancies?
AB - For the last three decades, metalloenzymes such as histone deacetylases (HDACs)
and matrix metalloproteinases (MMPs) have been identified in promoting solid as
well as hematological carcinogenesis. Histone deacetylase 8 (HDAC-8), a class I
HDAC enzyme, may serve as 'epigenetic player' that affects in the regulation of
transcription factors and alters the structure of chromosome associated with
tumorigenesis. It is established that the influence of MMP-2 in invasion,
metastasis and angiogenenic events of hematological malignancies may be
suppressed by HDAC inhibitors through reversion-inducing-cysteine-rich protein
with kazal motifs (RECK) protein. Therefore, the isoform-specific HDAC-8 and MMP
2 inhibitors may provide synergistic medicinal benefit in leukemia. However, a
paucity of articles is available on dual acting HDAC-8/MMP-2 inhibitors. In this
circumstance, a lot of works are still necessary to identify novel dual HDAC
8/MMP-2 inhibitors and this review will surely provide an initial idea regarding
the utility of designing such type of dual inhibitors. Here, the importance of
MMP-2 and HDAC-8 inhibition in hematological malignancies are focussed for the
first time as per our knowledge along with the structure-activity relationships
(SARs) of a handful of molecules, some of which were synthesised in-house, have
been highlighted that will inspire more interactions between the medicinal
chemistry and biology community to harness their expertise in design and
discovery of the better acting dual inhibitors in future.
PMID- 28501517
TI - Nanoparticles for modulating tumor microenvironment to improve drug delivery and
tumor therapy.
AB - Tumor microenvironment (TME) plays a critical role in tumorigenesis, tumor
invasion and metastasis. TME is composed of stroma, endothelial cells, pericytes,
fibroblasts, smooth muscle cells, and immune cells, which is characterized by
hypoxia, acidosis, and high interstitial fluid pressure. Due to the important
role of TME, we firstly reviewed the composition of TME and discussed the impact
of TME on tumor progression, drug and nanoparticle delivery. Next, we reviewed
current strategies developed to modulate TME, including modulating tumor
vasculature permeability, tumor associated macrophage phenotypes, tumor
associated fibroblasts, tumor stroma components, tumor hypoxia, and multiple
interventions simultaneously. Also, potential problems and future directions of
TME modulation strategy have been discussed.
PMID- 28501518
TI - Cannabidiol in medical marijuana: Research vistas and potential opportunities.
AB - The high and increasing prevalence of medical marijuana consumption in the
general population invites the need for quality evidence regarding its safety and
efficacy. Herein, we synthesize extant literature pertaining to the
phytocannabinoid cannabidiol (CBD) and its brain effects. The principle
phytocannabinoid Delta9-tetrahydrocannabinol (Delta9-THC) and CBD are the major
pharmacologically active cannabinoids. The effect of CBD on brain systems as well
as on phenomenological measures (e.g. cognitive function) are distinct and in
many cases opposite to that of Delta9-THC. Cannabidiol is without euphoriant
properties, and exerts antipsychotic, anxiolytic, anti-seizure, as well as anti
inflammatory properties. It is essential to parcellate phytocannabinoids into
their constituent moieties as the most abundant cannabinoid have differential
effects on physiologic systems in psychopathology measures. Disparate findings
and reports related to effects of cannabis consumption reflect differential
relative concentration of Delta9-THC and CBD. Existing literature,
notwithstanding its deficiencies, provides empirical support for the hypothesis
that CBD may exert beneficial effects on brain effector systems/substrates
subserving domain-based phenomenology. Interventional studies with purified CBD
are warranted with a call to target-engagement proof-of-principle studies using
the research domain criteria (RDoC) framework.
PMID- 28501519
TI - The Utility of Cardiac Magnetic Resonance Imaging in the Diagnosis of Cardiac
Sarcoidosis.
AB - BACKGROUND: Autopsy reports suggest that cardiac sarcoidosis occurs in 20 to 25%
of patients with pulmonary sarcoidosis, yet the clinical ante-mortem diagnosis is
made in only 5% of cases. Current diagnostic algorithms are complex and lack
sensitivity. Cardiac Magnetic Resonance imaging (CMR) provides an opportunity to
detect myocardial involvement in sarcoidosis. The aim of this study is to
determine the prevalence and clinical significance of late gadolinium enhancement
(LGE) on CMR in patients with sarcoidosis. METHODS: Consecutive patients with
biopsy-proven sarcoidosis undergoing CMR were retrospectively evaluated for
cardiac sarcoidosis. Medical records were correlated with CMR. RESULTS: Forty-six
patients were evaluated. Late gadolinium enhancement was present in 22%,
indicating myocardial involvement, and 70% had corresponding hyper-intense T2
signal indicating active inflammation. Late gadolinium enhancement was 18%+/-9.7%
of overall left ventricular (LV) mass and most commonly located in the basal to
mid septum. There was no association between LGE and cardiovascular symptoms or
pulmonary stage. Eighty per cent of patients with LGE did not fulfill
conventional diagnostic criteria for cardiac sarcoidosis. However, LGE was
associated with clinically significant arrhythmia (p<0.01) and a lower LVEF
(p=0.04). CONCLUSIONS: Using CMR, we identified a higher prevalence of cardiac
sarcoidosis than previously reported clinical studies, a prevalence which is more
consistent with autopsy data. The presence of LGE was highly correlated with
clinically significant arrhythmias and lower LVEF.
PMID- 28501520
TI - Can Heart Failure With Preserved Ejection Fraction Shed Light on the Mortality
Readmissions Paradox?
PMID- 28501521
TI - Associations Between Short or Long Length of Stay and 30-Day Readmission and
Mortality in Hospitalized Patients With Heart Failure.
AB - OBJECTIVES: This study sought to examine the associations between heart failure
(HF)-related hospital length of stay and 30-day readmissions and HF hospital
length of stay and mortality rates. BACKGROUND: Although reducing HF readmission
and mortality rates are health care priorities, how HF-related hospital length of
stay affects these outcomes is not fully known. METHODS: A population-level,
multicenter cohort study of 58,230 patients with HF (age >65 years) was conducted
in Ontario, Canada between April 1, 2003 and March 31, 2012. RESULTS: When length
of stay was modeled as continuous variable, its association with the rate of
cardiovascular readmission was nonlinear (p < 0.001 for nonlinearity) and U
shaped. When analyzed as a categorical variable, there was a higher rate of
cardiovascular readmission for short (1 to 2 days; adjusted hazard ratio [HR]:
1.12; 95% confidence interval [CI]: 1.04 to 1.21; p = 0.003) and long (9 to 14
days; HR: 1.11; 95% CI: 1.04 to 1.19; p = 0.002) lengths of stay as compared with
5 to 6 days (reference). Hospital readmissions for HF demonstrated a similar
nonlinear (p = 0.005 for nonlinearity) U-shaped relationship with increased rates
for short (HR: 1.15; 95% CI: 1.04 to 1.27; p = 0.006) and long (HR: 1.14; 95% CI:
1.04 to 1.25; p = 0.004) lengths of stay. Noncardiovascular readmissions
demonstrated increased rates with long (HR: 1.17; 95% CI: 1.07 to 1.29; p <
0.001) and decreased rates with short (HR: 0.87; 95% CI: 0.79 to 0.96; p = 0.006)
lengths of stay (p = 0.53 for nonlinearity). The 30-day mortality risk was
highest after a long length of stay (HR: 1.28; 95% CI: 1.14 to 1.43; p < 0.001).
CONCLUSIONS: A short length of stay after hospitalization for HF is associated
with increased rates of cardiovascular and HF readmissions but lower rates of
noncardiovascular readmissions. A long length of stay is associated with
increased rates of all types of readmission and mortality.
PMID- 28501522
TI - Long-Term Effects of Flosequinan on the Morbidity and Mortality of Patients With
Severe Chronic Heart Failure: Primary Results of the PROFILE Trial After 24
Years.
AB - OBJECTIVES: The purpose of this clinical trial was to evaluate the long-term
effects of flosequinan on the morbidity and mortality of patients with severe
chronic heart failure. BACKGROUND: Flosequinan was the first oral vasodilator to
be used in the clinic to augment the effects of digitalis, diuretics, and
angiotensin-converting enzyme inhibitors in heart failure. However, the drug
activated neurohormonal systems and exerted both positive inotropic and
chronotropic effects, raising concerns about its safety during long-term use.
METHODS: Following a run-in period designed to minimize the risk of tachycardia,
we randomly assigned 2,354 patients in New York Heart Association functional
class III to IV heart failure and with an ejection fraction <=35% to receive long
term treatment with placebo or flosequinan (75 or 100 mg/day) in addition to
their usual therapy. The primary outcome was all-cause mortality. RESULTS: The
trial was terminated after a recommendation of the Data and Safety Monitoring
Board, because during an average of 10 months of follow-up, 192 patients died in
the placebo group and 255 patients died in the flosequinan group (hazard ratio:
1.39, 95% confidence interval: 1.15 to 1.67; p = 0.0006). Flosequinan also
increased the risk of disease progression, which was paralleled by drug-related
increases in heart rate and neurohormonal activation. However, during the first
month, patients in the flosequinan group were more likely to report an
improvement in well-being and less likely to experience worsening heart failure.
Similarly, during the month following drug withdrawal at the end of the trial,
patients withdrawn from flosequinan were more likely than those withdrawn from
placebo to report symptoms of or to require treatment for worsening heart
failure. CONCLUSIONS: Although flosequinan produced meaningful symptomatic
benefits during short- and long-term treatment, the drug increased the risk of
death in patients with severe chronic heart failure.
PMID- 28501524
TI - Holding the Readmission Gates: Incentivizing Quality and Cost-Effective Care for
Heart Failure.
PMID- 28501523
TI - A New Clinically Applicable Measure of Functional Status in Patients With Heart
Failure: The 60-Foot Walk Test.
AB - OBJECTIVES: This study reports the development and predictive value of the 60
foot walk test (60ftWT), a brief functional status measure for patients with
heart failure (HF). The goal was to develop a test suitable for clinical settings
and appropriate for patients with walking impairments. BACKGROUND: The 6-min walk
test (6MWT) has considerable predictive value, but requires a long walking course
and has limited utility in patients with mobility-related comorbidities. A
shorter, more clinically practical test is therefore needed. METHODS: A total of
144 patients (age 57.4 +/- 11.4 years; 111 males) with symptomatic HF received
baseline assessments using the 60ftWT, 6MWT, and self-reported symptom and health
status. Patients were tested 3 months later to determine stability of
assessments. HF hospitalizations or death from any cause were recorded for 3.5
years following baseline. RESULTS: Median 60ftWT completion time was 26 s
(interquartile range: 22 to 31 s). Longer 60ftWT time was associated with shorter
6MWT distance (r = -0.75; p < 0.001), and with higher symptom severity at
baseline (r = -0.40; p < 0.001). Longer 60ftWT times also predicted increases in
6MWT and symptoms from baseline to 3 months (p < 0.01). Both WTs predicted long
term clinical outcomes, with patients taking longer than 31 s to complete the
60ftWT at greatest risk for HF hospitalization or death (hazard ratio: 2.13; 95%
confidence interval: 1.18 to 3.84; p = 0.01). CONCLUSIONS: The 60ftWT is an
easily administered functional status measure that predicts adverse events,
symptoms, and health status. It has the potential for considerable clinical
utility to help identify patients at risk for future events and to calibrate
treatments designed to improve functional status and quality of life.
PMID- 28501525
TI - Tetralogy of Fallow: Four Trials and Tribulations.
PMID- 28501526
TI - Do We Need Another Walking Test?
PMID- 28501529
TI - Hepatocellular carcinoma diagnosis and surveillance: Socioeconomic factors don't
seem to matter, unless you are an immigrant.
PMID- 28501527
TI - Race/Ethnic Differences in Outcomes Among Hospitalized Medicare Patients With
Heart Failure and Preserved Ejection Fraction.
AB - OBJECTIVES: This study analyzed HFpEF patient characteristics and clinical
outcomes according to race/ethnicity and adjusted for patient and hospital
characteristics along with socioeconomic status (SES). BACKGROUND: The proportion
of hospitalizations for heart failure with preserved ejection fraction (HFpEF)
has increased over the last decade. Whether the short- and long-term outcomes
differ between racial/ethnic groups is not well described. METHODS: The Get With
The Guidelines-Heart Failure registry was linked to Medicare administrative data
to identify hospitalized patients with HFpEF >=65 years of age with left
ventricular ejection fraction >=50% between 2006 and 2014. Cox proportional
hazards models were used to report hazard ratios (HRs) for 30-day and 1-year
readmission and mortality rates with sequential adjustments for patient
characteristics, hospital characteristics, and SES. RESULTS: The final cohort
included 53,065 patients with HFpEF. Overall 30-day mortality was 5.87%; at 1
year, it was 33.1%. The 30-day all-cause readmission rate was 22.2%, and it was
67.0% at 1 year. After adjusting for patient characteristics, hospital
characteristics, and SES, 30-day mortality was lower for black patients (HR:
0.84; 95% confidence interval [CI]: 0.71 to 0.98; p = 0.031) and Hispanic
patients (HR: 0.78; 95% CI: 0.64 to 0.96; p = 0.017) compared with white
patients. One-year mortality was lower for black patients (HR: 0.93; 95% CI: 0.87
to 0.99; p = 0.031), Hispanic patients (HR: 0.83; 95% CI: 0.75 to 0.91; p <
0.001), and Asian patients (HR: 0.76; 95% CI: 0.66 to 0.88; p < 0.001) compared
with white patients. Black patients had a higher risk of readmission at 30 days
(HR: 1.09; 95% CI: 1.02 to 1.16; p = 0.012) and 1 year (HR: 1.14; 95% CI: 1.09 to
1.20; p < 0.001) compared with white patients. CONCLUSIONS: Black, Hispanic, and
Asian patients had a lower mortality risk after a hospitalization for HFpEF
compared with white patients; black patients had higher readmission rates. These
differences in mortality and readmission risk according to race/ethnicity
persisted after adjusting for patient characteristics, SES, and hospital factors.
PMID- 28501530
TI - Adsorption of plasma proteins onto PEGylated single-walled carbon nanotubes: The
effects of protein shape, PEG size and grafting density.
AB - Single-walled carbon nanotubes (SWCNTs) covalently functionalized or
noncovalently coated with polyethylene glycol (PEG) of different sizes (Mw=2000
and 5000) and grafting densities (5-16 PEGs per SWCNT) are simulated with human
fibrinogen (HFG) and serum albumin (HSA). Proteins migrate toward the SWCNT, but
their adsorption extents differ. The extent of the HFG-SWCNT binding decreases
with increasing PEG size and grafting density because PEGs more completely cover
SWCNTs and thus block hydrophobic interactions between HFGs and SWCNTs, which
occurs on PEG-functionalized SWCNTs but not on PEG-coated ones. In particular,
the HFG-SWCNT binding significantly decreases in the transition region of PEG
conformation from mushroom to brush, where PEGs extend like brushes as described
in the Alexander-de Gennes theory. While the HFG adsorption is modulated by PEG
conformation, the HSA adsorption is much weaker and less influenced by PEG,
because spherical HSAs can bind to the restricted area of the SWCNT and thus
cannot bind to the SWCNT as tightly as do linear HFGs. These findings agree with
experiments showing less adsorption of proteins on the SWCNT functionalized with
larger and more PEGs, and support experimental suggestions regarding the
dependence of protein adsorption on protein shape and the mushroom-brush
transition of PEG conformation.
PMID- 28501531
TI - Symmetry in normal modes and its strong dependence on symmetry in structure.
AB - In this work, we look at the symmetry of normal modes in symmetric structures,
particularly structures with cyclic symmetry. We show that normal modes of
symmetric structures have different levels of symmetry, or symmetricity. One
novel theoretical result of this work is that, for a ring structure with m
subunits, the symmetricity of the normal modes falls into m groups of equal size,
with normal modes in each group having the same symmetricity. The normal modes in
each group can be computed separately, using a much smaller amount of memory and
time (up to m3 less). Lastly, we show that symmetry in normal modes depends
strongly on symmetry in structure. This work suggests a deeper reason for the
existence of symmetric complexes: that they may be formed not only for structural
purpose, but likely also for a dynamical reason, that certain structural symmetry
is needed to obtain certain symmetric motions that are functionally critical.
PMID- 28501532
TI - Targeted inhibition of Klotho binding to fibroblast growth factor 23 prevents
hypophosphetemia.
AB - Klotho is a transmembrane protein which plays significant role in the
pathogenesis of phosphate ion (Pi)-related disorders. Pi accumulation in human
kidney tissues results in the major metabolic disorders due to malfunctioning of
Klotho-FGFR1-FGF23 trimeric complex. The potential role of Klotho in Pi
metabolism was elaborated through modeling and interaction analysis of glycosyl
hydrolase (GS1 and GS2) domains with Fibroblast growth factor 23 (FGF23). In
order to inhibit the association of Klotho and FGF23, binding patterns of three
reported hits (N-(2-chlorophenyl)-1H-indole-3-carboxamide, N-[2-(1-cyclohexen-1
yl)ethyl]-6,7,8,9-tetrahydropyrido[1,2-e]purin-4-amine and 2-(1-propyl)amino-11
chlorothiazolo[5,4-a]acridine) were evaluated through molecular docking analysis.
These inhibitors effectively targeted both GS1 and GS2 domains of Klotho at the
similar sites required for FGF23 binding. To further characterize the comparative
binding profile of these compounds, molecular dynamics simulation assays were
performed. Taken together, current study emphasizes that Klotho may be
anticipated as a target molecule in familial hypophosphatemic rickets and
mentioned compounds may prove to be effective therapeutic targets against
hypophosphetemia induced disorders.
PMID- 28501528
TI - BCKDK of BCAA Catabolism Cross-talking With the MAPK Pathway Promotes
Tumorigenesis of Colorectal Cancer.
AB - Branched-chain amino acids catabolism plays an important role in human cancers.
Colorectal cancer is the third most commonly diagnosed cancer in males and the
second in females, and the new global incidence is over 1.2 million cases. The
branched-chain alpha-keto acid dehydrogenase kinase (BCKDK) is a rate-limiting
enzyme in branched-chain amino acids catabolism, which plays an important role in
many serious human diseases. Here we investigated that abnormal branched-chain
amino acids catabolism in colorectal cancer is a result of the disease process,
with no role in disease initiation; BCKDK is widely expressed in colorectal
cancer patients, and those patients that express higher levels of BCKDK have
shorter survival times than those with lower levels; BCKDK promotes cell
transformation or colorectal cancer ex vivo or in vivo. Mechanistically, BCKDK
promotes colorectal cancer by enhancing the MAPK signaling pathway through direct
MEK phosphorylation, rather than by branched-chain amino acids catabolism. And
the process above could be inhibited by a BCKDK inhibitor, phenyl butyrate.
PMID- 28501534
TI - Glomus Tumor of the Stomach-A Tumor That Needs to Be Differentiated From
Gastrointestinal Stromal Tumor.
PMID- 28501533
TI - Promising Modalities to Identify and Monitor Eosinophilic Esophagitis.
AB - Eosinophilic esophagitis (EoE) is an allergen-mediated condition characterized by
symptoms of esophageal dysfunction and histologic evidence of intense
eosinophilic inflammation involving the esophagus in the absence of overlapping
conditions such as gastroesophageal reflux disease. Since the initial description
as a distinct entity approximately 2 decades ago, there has been a remarkable
increase in the recognition of this clinicopathologic entity. The current
approach to diagnose and monitor EoE requires repeated
esophagogastroduodenoscopies, with associated sedation/anesthesia, to visualize
mucosal abnormalities, and to obtain multiple biopsy specimens for histologic
assessment and to evaluate treatment response. Frequent
esophagogastroduodenoscopies with multiple biopsies can increase the risk of
procedural complications, place significant financial burden on families, and
escalate health care costs. In addition, this burdensome approach may contribute
toward delayed diagnosis and suboptimal monitoring, thereby increasing the
likelihood of complications such as esophageal narrowing and stricture formation,
which may require escalation of care including endoscopic interventions. Clinical
progression and complications associated with EoE can be attenuated through early
identification and optimal management. Therefore, developing reliable, safe, less
cumbersome, and cost-effective modalities for early diagnosis and effective
monitoring of EoE is an area of active research. These efforts have been
substantially supported by the development of new biomaterials, analytic
methodologies, and the application of novel concepts. Herein, we summarize
modalities that have shown promise to advance the diagnosis and monitoring of EoE
and could improve the care of affected individuals and advance the field.
PMID- 28501535
TI - High Negative Predictive Value, Low Prevalence, and Spectrum Effect: Caution in
the Interpretation.
PMID- 28501536
TI - Multicenter External Validation of Risk Stratification Criteria for Patients With
Variceal Bleeding.
AB - BACKGROUND & AIMS: Early placement of a transjugular intrahepatic portosystemic
shunts (TIPS) is considered the treatment of choice for patients with acute
variceal bleeding (AVB) and cirrhosis who have a high risk of death (Child-Pugh
class B with active bleeding at endoscopy or Child-Pugh class C). It has been
proposed that patients of Child-Pugh class B, even with active bleeding, should
not be considered high risk. Alternative criteria have been proposed for
identification of high-risk patients, such as Child-Pugh class C with plasma
level of creatinine of 1 mg/dL or more (ChildC-C1) and a model for end-stage
liver disease (MELD) score of 19 or more. We analyzed outcomes of a large cohort
of patients with AVB who received the standard of care at different centers to
validate these systems of risk stratification. METHODS: We performed an
observational study of 915 patients with liver cirrhosis and AVB who received
standard treatment (drugs, antibiotics, and endoscopic ligation, with TIPS as the
rescue treatment), over different time periods between 2006 and 2014 in Canada
and Europe. All patients were followed until day 42 (week 6) after index AVB or
death. Child-Pugh and MELD scores were calculated at time of hospital admission.
The primary outcome was mortality 6 weeks after index AVB among patients who met
the early TIPS criteria (Child-Pugh class B with active bleeding at endoscopy or
Child-Pugh class C), MELD19 criteria (patients with MELD scores of 19 or more),
and ChildC-C1 criteria. RESULTS: Among 915 patients with AVB, 18% died within 6
weeks. Among the 523 patients who met the early TIPS criteria, 17% died within 6
weeks. All 3 rules discriminated patients at high risk of death from those with
low risk: 28.3% of the patients classified as high risk by the early TIPS
criteria died whereas only 7.0% of patients classified as low risk died; 46.0% of
patients classified as high risk by the MELD19 criteria died vs 8.1% of patients
classified as low risk; 51.9% of patients classified as high risk by the ChildC
C1 criteria died compared with 10.9% of patients classified as low risk.
Mortality was significantly lower among patients with Child-Pugh class B (11.7%)
than with Child-Pugh class C (35.6%) (P <= .001). Mortality was similar between
patients with Child-Pugh class B cirrhosis with or without active bleeding
(11.7%). Patients with Child-Pugh class A cirrhosis or MELD scores of 11 or less
had low mortality (2%-4%), patients with Child-Pugh class B cirrhosis or MELD
scores of 12 to 18 had intermediate mortality (10%-12%), and patients with Child
Pugh class C cirrhosis or MELD scores of 19 or more had high mortality (22%-46%).
CONCLUSIONS: Patients with Child-Pugh class B cirrhosis and AVB who receive
standard therapy, regardless of the presence of active bleeding, have 3-fold
lower mortality than patients with Child-Pugh C cirrhosis and might not need
TIPS. Patients with Child-Pugh class C and/or MELD scores of 19 or more should be
considered at high risk of death. These findings might help refine criteria for
early TIPS.
PMID- 28501537
TI - Effects of Exercise on Liver Fat and Metabolism in Alcohol Drinkers.
AB - BACKGROUND & AIMS: Exercise is an important component of obesity-associated
disorders and has been shown to reduce markers of nonalcoholic fatty liver
disease (NAFLD). However, little is known about how these effects are influenced
by alcohol intake. The authors performed a randomized controlled trial to
investigate the effects of exercise on hepatic triglyceride content (HTGC) and
metabolism in overweight or obese patients who consume alcohol. METHODS: The
authors performed a prospective study of 27 patients (mean 54 +/- 11 years of
age, body mass index [BMI] 31 +/- 4 kg/m2) with >5% HTGC in the United Kingdom,
consuming alcohol (mean 221 +/- 75 g/week). Anthropometry, body composition,
HTGC, and abdominal fat were measured using plethysmography and magnetic
resonance imaging. Subjects were assigned to groups that exercised (3 times/week
on nonconsecutive days) for 12 weeks (n = 14) or continued standard care (control
group, n = 13), maintaining baseline weight and alcohol consumption. The exercise
program consisted of aerobic exercise (static cycling) and a circuit of
resistance exercise (free weights and machines). Patients were examined at
baseline and at 12 weeks; data collected on HTGC, body composition, metabolic
control, circulating inflammatory, and fibrosis markers were assessed at baseline
and at 12 weeks. Between-group differences were evaluated using an unpaired t
test and within-group differences using a paired t test. The primary outcomes for
this study were changes in HTGC between baseline and 12 weeks. RESULTS: After 12
weeks, there was no significant difference between the exercise and control
groups in HTGC (reduction of 0.1% +/- 2.1% in exercisers vs increase of 0.5 +/-
2.1% in control group; P > .05). At week 12, the exercise group had significant
reductions in subcutaneous fat (loss of 23 +/- 28 cm2 in the exercisers vs
increase of 12 +/- 19 cm2 in the control group; P < .01), and whole body fat
(loss of 2.1 +/- 1.1 kg in the exercisers vs increase of 0.2 +/- 2.1 kg; P <
.01). The exercise group also had a significantly greater increase in lean body
mass (increase of 1.9 +/- 1.4 kg for the exercisers vs increase of 0.7 +/- 1.5 kg
for the control group; P < .01) and a significantly greater reduction in level of
cytokeratin 18 (reduction of 49 +/- 82 U/L in exercisers vs increase of 17 +/- 38
U/L in control group; P < .05). There were no differences between groups in
changes in metabolic factors or markers of inflammation. CONCLUSIONS: In a
randomized controlled trial of obese individuals who consume alcohol, exercise
significantly improved body composition and reduced hepatocyte apoptosis
(cytokeratin 18), but did not reduce HTGC. This finding could indicate that
alcohol consumption reduces the effects of exercise on NAFLD observed in previous
studies. Clinical care teams should look to use exercise as part of the
management strategy for people consuming alcohol, but optimal benefit may be as
an adjunct to alcohol reduction and weight management strategies. (ISRCTN.com,
Number: ISRCTN90597099).
PMID- 28501538
TI - Biopsy Specimens From Allograft Liver Contain Histologic Features of Hepatitis C
Virus Infection After Virus Eradication.
AB - BACKGROUND & AIMS: Most patients, even those who have received a liver
transplant, achieve a sustained virologic response (SVR) to therapy for hepatitis
C virus (HCV) infection. Little is known about the histologic features of liver
biopsy specimens collected after SVR, particularly in patients who have received
a liver transplant. We aimed to better characterize the histologic features of
allograft liver biopsy specimens from patients who achieved SVR to anti-HCV
therapy after liver transplantation. METHODS: We performed a retrospective
analysis of 170 allograft liver biopsy specimens from 36 patients who received a
liver transplant for chronic HCV infection, had recurrent HCV infection after
transplantation, and subsequently achieved SVR (collected from 1999 through 2015
at 4 medical centers). SVR was defined as an undetectable serum HCV RNA level 24
weeks after completion of HCV treatment. A total of 65 biopsy specimens were post
SVR (at least 1 post-SVR from each patient; some biopsy specimens were collected
at later time points from a subset of patients). We performed polymerase chain
reaction analysis for HCV RNA on a subset of the biopsy specimens (28 collected
before SVR and 32 after SVR). RESULTS: Of the 65 post-SVR biopsy specimens, 45
(69%) had histologic features of active HCV infection. Of the initial post-SVR
biopsy specimens collected from each of the 36 patients, 32 (89%) showed these
changes. For patients with more than 1 post-SVR biopsy specimen, 6 (46%) had no
change in fibrosis between biopsies, and fibrosis worsened for 3 patients (23%)
based on their most recent biopsy. The HCV RNA level was undetectable in 31 of
the 32 biopsy specimens analyzed by polymerase chain reaction. CONCLUSIONS: In a
retrospective analysis of allograft liver biopsy specimens from patients who
achieved SVR after a liver transplant for chronic HCV infection, histologic
changes associated with active HCV were present in 69% and fibrosis continued to
progress in 23%, despite the lack of detection of HCV RNA. Pathologists should be
aware of patients' SVR status when analyzing liver biopsy specimens to avoid
diagnoses of chronic HCV-associated hepatitis. Because of the persistent
inflammatory activity and fibrosis after SVR, clinicians should continue to
monitor patients carefully after SVR to anti-HCV therapy.
PMID- 28501540
TI - FT-IR spectroscopic study of amyloid protein formation and aortic valve
calcification.
PMID- 28501539
TI - Spatiotemporal oscillatory dynamics of visual selective attention during a
flanker task.
AB - The flanker task is a test of visual selective attention that has been widely
used to probe error monitoring, response conflict, and related constructs.
However, to date, few studies have focused on the selective attention component
of this task and imaged the underlying oscillatory dynamics serving task
performance. In this study, 21 healthy adults successfully completed an arrow
based version of the Eriksen flanker task during magnetoencephalography (MEG).
All MEG data were pre-processed and transformed into the time-frequency domain.
Significant oscillatory brain responses were imaged using a beamforming approach,
and voxel time series were extracted from the peak responses to identify the
temporal dynamics. Across both congruent and incongruent flanker conditions, our
results indicated robust decreases in alpha (9-12Hz) activity in medial and
lateral occipital regions, bilateral parietal cortices, and cerebellar areas
during task performance. In parallel, increases in theta (3-7Hz) oscillatory
activity were detected in dorsal and ventral frontal regions, and the anterior
cingulate. As per conditional effects, stronger alpha responses (i.e., greater
desynchronization) were observed in parietal, occipital, and cerebellar cortices
during incongruent relative to congruent trials, whereas the opposite pattern
emerged for theta responses (i.e., synchronization) in the anterior cingulate,
left dorsolateral prefrontal, and ventral prefrontal cortices. Interestingly, the
peak latency of theta responses in these latter brain regions was significantly
correlated with reaction time, and may partially explain the amplitude difference
observed between congruent and incongruent trials. Lastly, whole-brain
exploratory analyses implicated the frontal eye fields, right temporoparietal
junction, and premotor cortices. These findings suggest that regions of both the
dorsal and ventral attention networks contribute to visual selective attention
processes during incongruent trials, and that such differential processes are
transient and fully completed shortly after the behavioral response in most
trials.
PMID- 28501541
TI - Characteristics Associated with Treatment Response and Satisfaction in Women
Undergoing OnabotulinumtoxinA and Sacral Neuromodulation for Refractory Urgency
Urinary Incontinence.
AB - PURPOSE: We sought to identify clinical and demographic characteristics
associated with treatment response and satisfaction in women undergoing
onabotulinumtoxinA and sacral neuromodulation therapies. MATERIALS AND METHODS:
We analyzed data from the ROSETTA (Refractory Overactive Bladder: Sacral
NEuromodulation versus BoTulinum Toxin Assessment) trial. Baseline participant
characteristics and clinical variables were associated with 2 definitions of
treatment response, including 1) a reduction in mean daily urgency incontinence
episodes during 6 months and 2) a 50% or greater decrease in urgency incontinence
episodes across 6 months. The OAB-S (Overactive Bladder-Satisfaction)
questionnaire was used to assess satisfaction. RESULTS: A greater reduction in
mean daily urgency incontinence episodes was associated with higher HUI-3 (Health
Utility Index-3) scores in the onabotulinumtoxinA group and higher baseline
incontinence episodes (each p <0.001) in the 2 groups. Increased age was
associated with a lesser decrease in incontinence episodes in the 2 groups (p
<0.001). Increasing body mass index (adjusted OR 0.82/5 points, 95% CI 0.70-0.96)
was associated with reduced achievement of a 50% or greater decrease in
incontinence episodes after each treatment. Greater age (adjusted OR 0.44/10
years, 95% CI 0.30-0.65) and a higher functional comorbidity index (adjusted OR
0.84/1 point, 95% CI 0.71-0.99) were associated with reduced achievement of a 50%
or greater decrease in urgency incontinence episodes in the onabotulinumtoxinA
group only (p <0.001 and 0.041, respectively). In the onabotulinumtoxinA group
increased satisfaction was noted with higher HUI-3 score (p = 0.002) but there
was less satisfaction with higher age (p = 0.001). CONCLUSIONS: Older women with
multiple comorbidities, and decreased functional and health related quality of
life had decreased treatment response and satisfaction with onabotulinumtoxinA
compared to sacral neuromodulation for refractory urgency incontinence.
PMID- 28501542
TI - Metabolite profile of koji amazake and its lactic acid fermentation product by
Lactobacillus sakei UONUMA.
AB - The koji amazake is a traditional sweet Japanese beverage. It has been consumed
for over a thousand years in Japan; nonetheless, little is yet known of the
ingredients in koji amazake. Therefore, this study aimed to analyze the
metabolites of koji amazake using a metabolomics approach. Additionally, we
reformed the flavor of koji amazake by lactic acid fermentation (LAF-amazake)
using Lactobacillus sakei UONUMA, which was isolated from snow caverns. The
purpose of this article is to identify the ingredients in these beverages. In LAF
amazake and koji amazake, sugars, amino acids, organic acids, and vitamin B
complex were determined in the two beverages, and over 300 compounds were
detected in total. Thirteen saccharides were identified including two unknown
trisaccharides, and there were no differences in these between the two beverages.
In LAF-amazake, lactic acid, vitamin B2 (riboflavin), B3 (nicotinic acid and
nicotinamide), and B6 (pyridoxine) were significantly increased as compared to
koji amazake, whereas malate and glutamine decreased. These results suggested
that LAF, malolactic fermentation, and glutamine deamidation occurred
simultaneously in LAF-amazake. L. sakei UONUMA strains produced these vitamins.
Moreover, it was surprising that acetylcholine, a well-known neurotransmitter,
was newly generated in LAF-amazake. Here, we have succeeded in reforming the
flavor of koji amazake and obtained these metabolic data on the two beverages.
The present study could provide useful basic information for promoting functional
analyses of koji amazake and LAF-amazake for human health.
PMID- 28501543
TI - Allogeneic Hematopoietic Stem Cell Transplantation for Adolescents and Young
Adults with Acute Myeloid Leukemia.
AB - Few reports have focused on adolescent and young adult (AYA) patients with acute
myeloid leukemia (AML) treated with hematopoietic stem cell transplantation
(HSCT). We performed a retrospective analysis based on data obtained from a
Japanese nationwide registration database to compare HSCT outcomes in AYA
patients with AML with those in children with AML. An analysis of the 2973
patients with de novo AML who received allogeneic HSCT from 1990 to 2013 showed
inferior 5-year overall survival (OS) (54% versus 58%, P <.01) and increased
treatment-related mortality (TRM) (16% versus 13%, P = .02) in AYA patients.
Multivariate analysis for both OS and TRM showed a significant negative impact on
AYAs. However, the negative impact of older age lost its significance in an
additional analysis focusing on 1407 recent transplant recipients with high
resolution HLA typing (2000 to 2013). Finally, we analyzed the impact of
transplantation center type on HSCT outcomes in 317 adolescent patients (15 to 18
years old) and found no difference in outcomes between patients treated at a
pediatric or an adult hospital. Higher age was a strong predictive factor for
inferior OS resulting from increased TRM, which can be eliminated with better
donor selection using high-resolution HLA typing.
PMID- 28501544
TI - The DNA methylation status alteration of two steroidogenic genes in gonads of
rare minnow after bisphenol A exposure.
AB - Both cytochrome P450c17 (CYP17A1) and P-450 side chain cleavage (CYP11A1) play
important roles in steroid biosynthesis. According to our previous studies,
bisphenol A (BPA) could regulate the mRNA expression of cyp17a1 and cyp11a1 in
rare minnow Gobiocypris rarus. However, the potential mechanism of the regulation
is barely understood. In the present study, aiming to explore how BPA affects the
mRNA expression of cyp17a1 and cyp11a1 in testes and ovaries of G. rarus, we
firstly cloned 340-bp fragment of 5' flanking region of cyp11a1 and then detected
the methylation level of CpG loci involved in 5' flanking of cyp11a1 and cyp17a1
and their mRNA expression levels. Results showed that exposure to BPA
significantly increased serum estradiol (E2) and 11-ketotesterone (11-KT)
concentrations. Ovarian mRNA expression of cyp17a1 and cyp11a1 were significantly
decreased after BPA exposure 7- for and 14-days. However, transcriptions of
testicular cyp17a1 and cyp11a1 were significantly increased and decreased
respectively after BPA treatment for 14days. The DNA methylation levels of
cyp17a1 were decreased in ovaries on day 7 and increased in ovaries and decreased
in testes respectively on day 14. The methylation levels of cyp11a1 were
increased in ovaries on day 7 and both ovaries and testes on day 14. There were a
significant correlation between DNA methylation at specific CpG loci and cyp17a1
and cyp11a1 genes transcription levels. In conclusion, the CpG loci methylation
in 5' flanking region appears to involve in the regulation of mRNA expression of
cyp17a1 and cyp11a1 mediated by BPA.
PMID- 28501545
TI - Betamethasone causes intergenerational reproductive impairment in male rats.
AB - Prenatal betamethasone (BM) exposure in rats negatively impacts sperm quality and
male fertility. Studies have shown that BM can cause multi-generational effects
on the pituitary-adrenal-axis of rats. The objective of this study was to assess
the reproductive development and fertility of male rats (F2) whose fathers (F1)
were exposed to BM (0.1mg/kg) on gestational days 12, 13, 18 and 19. In F2 rats,
there was a significant reduction in body weights of the BM-treated group at PND
1 as well as delayed onset of puberty, and decreases in FSH levels, Leydig cell
volume, sperm number and motility, seminal vesicle contractility and ejaculated
volume. Furthermore, increased serum LH levels, sperm DNA damage and abnormal
morphology were observed, resulting in reduced fertility. In conclusion, prenatal
BM-treatment leads to intergenerational long-term reproductive impairment in male
rats, raising concern regarding the widespread use of BM in preterm births.
PMID- 28501546
TI - Diagnosis of primary ciliary dyskinesia: When and how?
AB - INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare congenital disorder
involving permanent ubiquitous structural and/or functional ciliary
abnormalities. METHODS: A single-center retrospective study included 56 cases of
PCD (respiratory form) out of a cohort of 280 patients with suspected PCD. The
main features of history-taking and clinical examination were analyzed, to
formulate a pragmatic diagnostic procedure, easy to implement in clinical
practice. RESULTS: Chronic respiratory tract infectious symptoms are sensitive
but non-specific for the diagnosis of PCD. Nasal brushing for phase-contrast
microscopy study of ciliary morphology and activity proved to be a fast, easy,
non-invasive, cost-effective and age-independent diagnostic method. In doubtful
cases, depending on local availability, further tests are indicated: nasal nitric
oxide level, electronic microscopy, genetic study and cell culture. CONCLUSIONS:
In suspected PCD, there being no gold standard method of screening and early
diagnosis, nasal brushing with ciliary study is contributive, alongside numerous
other complementary tests, on condition that the clinician is experienced and
results are interpreted in the light of clinical examination and history-taking.
PMID- 28501547
TI - Drawn together: When motor representations ground joint actions.
AB - What enables individuals to act together? Recent discoveries suggest that a
variety of mechanisms are involved. But something fundamental is yet to be
investigated. In joint action, agents represent a collective goal, or so it is
often assumed. But how, if at all, are collective goals represented in joint
action and how do such representations impact performance? To investigate this
question we adapted a bimanual paradigm, the circle-line drawing paradigm, to
contrast two agents acting in parallel with two agents performing a joint action.
Participants were required to draw lines or circles while observing circles or
lines being drawn. The findings indicate that interpersonal motor coupling may
occur in joint but not parallel action. This suggests that participants in joint
actions can represent collective goals motorically.
PMID- 28501549
TI - The effect of phasic auditory alerting on visual perception.
AB - Phasic alertness refers to a short-lived change in the preparatory state of the
cognitive system following an alerting signal. In the present study, we examined
the effect of phasic auditory alerting on distinct perceptual processes,
unconfounded by motor components. We combined an alerting/no-alerting design with
a pure accuracy-based single-letter recognition task. Computational modeling
based on Bundesen's Theory of Visual Attention was used to examine the effect of
phasic alertness on visual processing speed and threshold of conscious
perception. Results show that phasic auditory alertness affects visual perception
by increasing the visual processing speed and lowering the threshold of conscious
perception (Experiment 1). By manipulating the intensity of the alerting cue, we
further observed a positive relationship between alerting intensity and
processing speed, which was not seen for the threshold of conscious perception
(Experiment 2). This was replicated in a third experiment, in which pupil size
was measured as a physiological marker of alertness. Results revealed that the
increase in processing speed was accompanied by an increase in pupil size,
substantiating the link between alertness and processing speed (Experiment 3).
The implications of these results are discussed in relation to a newly developed
mathematical model of the relationship between levels of alertness and the speed
with which humans process visual information.
PMID- 28501548
TI - Facilitation and interference in naming: A consequence of the same learning
process?
AB - Our success with naming depends on what we have named previously, a phenomenon
thought to reflect learning processes. Repeatedly producing the same name
facilitates language production (i.e., repetition priming), whereas producing
semantically related names hinders subsequent performance (i.e., semantic
interference). Semantic interference is found whether naming categorically
related items once (continuous naming) or multiple times (blocked cyclic naming).
A computational model suggests that the same learning mechanism responsible for
facilitation in repetition creates semantic interference in categorical naming
(Oppenheim, Dell, & Schwartz, 2010). Accordingly, we tested the predictions that
variability in semantic interference is correlated across categorical naming
tasks and is caused by learning, as measured by two repetition priming tasks
(picture-picture repetition priming, Exp. 1; definition-picture repetition
priming, Exp. 2, e.g., Wheeldon & Monsell, 1992). In Experiment 1 (77 subjects)
semantic interference and repetition priming effects were robust, but the results
revealed no relationship between semantic interference effects across contexts.
Critically, learning (picture-picture repetition priming) did not predict
semantic interference effects in either task. We replicated these results in
Experiment 2 (81 subjects), finding no relationship between semantic interference
effects across tasks or between semantic interference effects and learning
(definition-picture repetition priming). We conclude that the changes underlying
facilitatory and interfering effects inherent to lexical access are the result of
distinct learning processes where multiple mechanisms contribute to semantic
interference in naming.
PMID- 28501550
TI - Type 2 diabetes alters hippocampal gamma oscillations: A potential mechanism
behind impaired cognition.
AB - Type 2 diabetes (T2D) has been associated with cognitive decline, dementia and
Alzheimer's disease (AD). Remarkably, the pathophysiological mechanisms behind
this are still mostly unknown. Cognition and memory formation are associated with
gamma oscillations in hippocampal neuronal networks and fast-spiking, parvalbumin
expressing interneurons (PV+ IN) play a key role in these processes.
PMID- 28501551
TI - Contribution of stress and sex hormones to memory encoding.
AB - Distinct stages of the menstrual cycle and the intake of oral contraceptives (OC)
affect sex hormone levels, stress responses, and memory processes critically
involved in the pathogenesis of mental disorders. To characterize the interaction
of sex and stress hormones on memory encoding, 30 men, 30 women in the early
follicular phase of the menstrual cycle (FO), 30 women in the luteal phase (LU),
and 30 OC women were exposed to either a stress (socially evaluated cold-pressor
test) or a control condition prior to memory encoding and immediate recall of
neutral, positive, and negative words. On the next day, delayed free and cued
recall was tested. Sex hormone levels verified distinct estradiol, progesterone,
and testosterone levels between groups. Stress increased blood pressure, cortisol
concentrations, and ratings of stress appraisal in all four groups as well as
cued recall performance of negative words in men. Stress exposure in OC women led
to a blunted cortisol response and rather enhanced cued recall of neutral words.
Thus, pre-encoding stress facilitated emotional cued recall performance in men
only, but not women with different sex hormone statuses pointing to the pivotal
role of circulating sex hormones in modulation of learning and memory processes.
PMID- 28501552
TI - Taking turns across channels: Conversation-analytic tools in animal
communication.
AB - In the quest to bridge the gulf between the fields of linguistics and animal
communication, interest has recently been drawn to turn-taking behavior in social
interaction. Vocal turn-taking is the core form of language usage in humans, and
has been examined in numerous species of birds and primates. Recent studies on
great apes have shown that they engage in a bodily form, gestural turn-taking, to
achieve mutual communicative goals. However, most studies on turn-taking
neglected the fact that signals are prevalently perceived and produced in a
multimodal format. Here, I propose that research on animal communication may
benefit a more holistic and dynamic approach: studying turn-taking using a
multimodal, conservation-analytic framework. I will discuss recent comparative
research that implemented this approach via a specific set of parameters. In sum,
I argue that a conversation-analytic framework might help substantially to
pinpoint the ways in which crucial components of language are embodied in the
'human interaction engine'.
PMID- 28501553
TI - Progressive cortical reorganisation: A framework for investigating structural
changes in schizophrenia.
AB - One of the few well-replicated features of schizophrenia is the demonstration of
neuroanatomical abnormalities affecting cortical and subcortical grey matter
(GM). Evidence to date suggests that the greatest reduction in GM occurs in the
immediate post-onset phase. The predominant view to date is that the accelerated
grey matter (GM) loss represents an adverse process (degenerative or
developmental deficit) contributing to the unfavourable course of schizophrenia.
This prevailing emphasis on decompensation often overlooks the fact that human
brain has an inherent capacity to remodel itself in response to insults that
affect its function. In the wake of emerging insights into both micro- and macro
scale brain connectivity, a substantial amount of the longitudinal structural
changes seen in patients with schizophrenia could result from a distributed,
nevertheless inefficient, cortical reorganization response. Quantifying cortical
reorganization in the early stages of illness can enable prospective grading of
the underlying pathophysiological process in schizophrenia.
PMID- 28501554
TI - Molecular typing of Clostridium difficile isolates cultured from patient stool
samples and gastroenterological medical devices in a single Iranian hospital.
AB - This study aimed to characterize Clostridium difficile isolates cultured from
stool samples of patients with C. difficile infection (CDI) and swabs from a
medical environment in a gastroenterology center in Tehran, Iran. A total of 158
samples (105 stool samples from hospitalized patients and 53 swabs from medical
devices and the environment) were collected from January 2011 to August 2011 and
investigated for the presence of C. difficile by direct anaerobic culture on a
selective media for C. difficile. C. difficile isolates were further
characterized by capillary electrophoresis (CE) ribotyping and toxin gene
multiplex PCR. Of 158 samples, C. difficile was cultured in 19 of 105 stool
samples (18%) and in 4 of 53 swabs (7.5%). C. difficile PCR ribotype (RT) 126 was
the most common RT in the study (21.7%). Further RTs were: 001, 003, 014, 017,
029, 039, 081, 103 and 150. RTs 126, 001, 150 were cultured from both the stool
samples and swabs of medical devices and the hospital environment which suggest a
possible route of transmission.
PMID- 28501555
TI - Antitumor Effect of AZD4547 in a Fibroblast Growth Factor Receptor 2-Amplified
Gastric Cancer Patient-Derived Cell Model.
AB - BACKGROUND: FGFR2 amplification is associated with aggressive gastric cancer
(GC), and targeted drugs have been developed for treatment of GC. We evaluated
the antitumor activity of an FGFR inhibitor in FGFR2-amplified GC patients with
peritoneal carcinomatosis. METHODS: Two GC patients with FGFR2 amplification
confirmed by fluorescence in situ hybridization showed peritoneal seeding and
malignant ascites. We used the patient-derived xenograft model; patient-derived
cells (PDCs) from malignant ascites were used to assess FGFR2 expression and its
downstream pathway using immunofluorescence analysis and immunoblot assay in
vitro. Apoptosis and cell cycle arrest after treatment of FGFR inhibitor were
analyzed by Annexin V-FITC assay and cell cycle analysis. RESULTS: FGFR2
amplification was verified in both PDC lines. AZD4547 as an FGFR inhibitor
decreased proliferation of PDCs, and the IC50 value was estimated to be 250 nM in
PDC#1 and 210 nM in PDC#2. FGFR inhibitor also significantly decreased levels of
phosphorylated FGFR2 and downstream signaling molecules in FGFR2-amplified PDC
lines. In cell cycle analysis, apoptosis was significantly increased in AZD4547
treated cells compared with nontreated cells. The proportion of cells in the sub
G1 stage was significantly higher in AZD4547-treated PDCs than in control cells.
CONCLUSION: Our findings suggest that FGFR2 amplification is a relevant
therapeutic target in GC with peritoneal carcinomatosis.
PMID- 28501557
TI - The positive cognitive impact of aerobic fitness is associated with peripheral
inflammatory and brain-derived neurotrophic biomarkers in young adults.
AB - There is ample evidence for supporting the positive impact of aerobic fitness on
cognitive function, but little is known about the physiological mechanisms. The
objective of this study was to investigate whether the positive cognitive impact
of aerobic fitness is associated with inflammatory and neurotrophic peripheral
biomarkers in young adults aged 18 to 29years (n=87). For the objective
assessment of aerobic fitness, we measured maximal oxygen uptake (VO2max) as a
parametric measure of cardiorespiratory capacity. We demonstrated that young
adults with the higher levels of VO2max performed better on computerized
cognitive tasks assessing sustained attention and working memory. This positive
VO2max-cognitive performance association existed independently of confounders
(e.g., years of education, intelligence scores) but was significantly dependent
on resting peripheral blood levels of inflammatory (C-reactive protein, CRP) and
neurotrophic (brain-derived neurotrophic factor, BDNF) biomarkers. Statistical
models showed that CRP was a mediator of the effect of VO2max on working memory.
Further, BDNF was a moderator of the effect of VO2max on working memory. These
mediating and moderating effects occurred in individuals with higher levels of
aerobic fitness. The results suggest that higher aerobic fitness, as measured by
VO2max, is associated with enhanced cognitive functioning and favorable resting
peripheral levels of inflammatory and brain-derived neurotrophic biomarkers in
young adults.
PMID- 28501556
TI - Behavioral and physiological reactions in dogs to a veterinary examination: Owner
dog interactions improve canine well-being.
AB - In order to improve well-being of dogs during veterinary visits, we aimed to
investigate the effect of human social interactions on behavior and physiology
during routine examination. Firstly, we assessed the impact of a standardized
veterinary examination on behavioral and physiological indicators of stress in
dogs. Secondly, we examined whether the owner's tactile and verbal interactions
with the dog influenced behavioral and physiological stress-associated
parameters. A randomized within-subjects crossover design was used to examine
behavior (n=33), rectal temperature (n=33), heart rate (HR) (n=18), maximal
ocular surface temperature (max OST) (n=13) and salivary cortisol concentrations
(n=10) in healthy privately owned pet dogs. The study consisted of two
experimental conditions: a) "contact" - owner petting and talking to the dog
during the examination; b) "non-contact" - owner present during the examination
but not allowed to interact with the dog. Our findings showed that the veterinary
examinations produced acute stress responses in dogs during both "contact" and
"non-contact" conditions, with significant increases in lip licking, HR, and max
OST. A significant decrease in attempts to jump off the examination table
(p=0.002) was observed during the examination in the "contact" compared to the
"non-contact" condition. In addition, interactions of owners showed an
attenuating effect on HR (p=0.018) and max OST (p=0.011) in their dogs. The
testing order (first vs. second visit) had no impact on behavioral and
physiological parameters, suggesting that dogs did not habituate or sensitize to
the examination procedure. Moreover, the duration of the owner-dog interactions
had no significant impact on the behavioral and physiological responses of their
dogs. This study demonstrates that owner-dog interactions improve the well-being
of dogs during a veterinary examination. Future research may assist in further
understanding the mechanisms associated with reducing stress in dogs in similar
settings.
PMID- 28501558
TI - Effects of prolonged exposure to CO2 on behaviour, hormone secretion and
respiratory muscles in young female rats.
AB - Atmospheric CO2 concentrations increased significantly over the last century and
continuing increases are expected to have significant effects on current
ecosystems. This study evaluated the behavioural and physiological (hormone
status, muscle structure) effects of prolonged CO2 exposure in young female
Wistar rats exposed at 700ppm of CO2 during 6h a day for 15days. Prolonged CO2
exposure, though not continuous, produced significant disturbances in behaviour
with an increase in drinking, grooming and resting, and a reduction in rearing,
jumping-play and locomotor activity. Furthermore, CO2 exposure was accompanied by
increased plasma levels of corticosterone, suggesting that prolonged exposure to
CO2 was stressful. The muscular structure can also be modified also when
respiratory working conditions change. The expression of myosin heavy chain was
significantly affected in the diaphragm and oral respiratory muscles: Masseter
Superficialis and Anterior Digastric. Modified behaviour and hormonal changes
both appear to be at the origin of the observed muscular adaptation.
PMID- 28501559
TI - Fast, accurate and easy-to-teach QT interval assessment: The triplicate
concatenation method.
AB - BACKGROUND: The gold standard method for assessing the QTcF (QT corrected for
heart rate by Fridericia's cube root formula) interval is the "QTcF semiautomated
triplicate averaging method" (TAM), which consists of measuring three QTcF values
semiautomatically, for each 10-second sequence of a triplicate electrocardiogram
set, and averaging them to get a global and unique QTcF value. Thus, TAM is time
consuming. We have developed a new method, namely the "QTcF semiautomated
triplicate concatenation method" (TCM), which consists of concatenating the three
10-second sequences of the triplicate electrocardiogram set as if they were a
single 30-second electrocardiogram, and measuring QTcF only once for the
triplicate electrocardiogram set. AIM: To compare the TCM method with the TAM
method. METHODS: Fifty triplicate electrocardiograms were read twice by an expert
and a student using both methods (TAM and TCM). We plotted Bland-Altman plots to
assess agreement between the two methods, and to compare the student and expert
results. The time needed to read a set of 20 consecutive triplicate
electrocardiograms was measured. RESULTS: Limits of agreement between TAM and TCM
ranged from -8.25 to 6.75ms with the expert reader. TCM was twice as fast as TAM
(17.38 versus 34.28min for 20 consecutive triplicate electrocardiograms). Bland
Altman plots comparing student and expert results showed limits of agreement
ranging from -4.34 to 11.75ms for TAM, and -1.2 to 8.0ms for TCM. CONCLUSIONS:
TAM and TCM show good agreement for QT measurement. TCM is less time consuming
than TAM. After a learning session, an inexperienced reader can measure the QT
interval accurately with both methods.
PMID- 28501560
TI - The immune microenvironment and HPV in anal cancer: Rationale to complement
chemoradiation with immunotherapy.
AB - Anal squamous cell carcinomas (ASCC) are increasing in frequency across the
developed world, and 70-90% of all cases originate from infection with human
papilloma viruses (HPV). Primary chemoradiotherapy (CRT) is the standard
treatment for ASCC, but local and/or distant failure still occurs in up to 30% of
patients. HPV-associated ASCC and tumors with a higher density of tumor
infiltrating lymphocytes (TIL) carry a better prognosis. Furthermore, HPV can
render tumors more immunogenic, whereas it correlates with elevated TIL
densities. This comprehensive review highlights the progress made in
understanding the immune microenvironment of anal intraepithelial neoplasias and
ASCC in the context of HPV. Here, we discuss the immunomodulatory potential of
CRT, the prognostic impact of immune checkpoint markers, and the rationale for
including immunotherapies to further improve the clinical outcome in patients
with ASCC.
PMID- 28501561
TI - The sleeping ugly: Tumour microenvironment's act to make or break the spell of
dormancy.
AB - Metastasis is the main cause of death for most cancer patients. It appears clear
from clinical observations that the majority of cancers, particularly carcinoma
do not follow a linear model of metastatic progression, where cancer cells shed
from the primary tumour, disseminate to a distant organ and immediately outgrow
to form clinical metastasis. Certainly, while cancer spreading is an early event,
metastasis occurs much later during tumour progression and frequently arises
several years after primary tumour resection. The time spent by disseminated
cancer cells (DTCs) in a distant organ before their outgrowth is termed
metastatic latency. We will examine here the current knowledge of the mechanisms
allowing metastatic latency and discuss the crucial role of the DTCs' tissue
microenvironment in this process.
PMID- 28501562
TI - A 'joint venture' model of recontacting in clinical genomics: challenges for
responsible implementation.
AB - Advances in genomics often lead healthcare professionals (HCPs) to learn new
information, e.g., about reinterpreted variants that could have clinical
significance for patients seen previously. A question arises of whether HCPs
should recontact these former patients. We present some findings interrogating
the views of patients (or parents of patients) with a rare or undiagnosed
condition about how such recontacting might be organised ethically and
practically. Forty-one interviews were analysed thematically. Participants
suggested a 'joint venture' model in which efforts to recontact are shared with
HCPs. Some proposed an ICT-approach involving an electronic health record that
automatically alerts them to potentially relevant updates. The need for rigorous
privacy controls and transparency about who could access their data was
emphasised. Importantly, these findings highlight that the lack of clarity about
recontacting is a symptom of a wider problem: the lack of necessary
infrastructure to pool genomic data responsibly, to aggregate it with other
health data, and to enable patients/parents to receive updates. We hope that our
findings will instigate a debate about the way responsibilities for recontacting
under any joint venture model could be allocated, as well as the limitations and
normative implications of using ICT as a solution to this intractable problem. As
a first step to delineating responsibilities in the clinical setting, we suggest
HCPs should routinely discuss recontacting with patients/parents, including the
new information that should trigger a HCP to initiate recontact, as part of the
consent process for genetic testing.
PMID- 28501563
TI - Kindlin-1 protects cells from oxidative damage through activation of ERK
signalling.
AB - Kindlin-1 is a FERM domain containing adaptor protein that is found predominantly
at cell-extracellular matrix adhesions where it binds to beta-integrin subunits
and is required for integrin activation. Loss of function mutations in the FERMT1
gene which encodes Kindlin-1 leads to the development of Kindler Syndrome (KS) an
autosomal recessive skin disorder characterized by skin blistering,
photosensitivity, and predisposition to aggressive squamous cell carcinoma (SCC).
Here we show that loss of Kindlin-1 sensitizes both SCC cells and keratinocytes
to oxidative stress: Kindlin-1 deficient cells have higher levels of reactive
oxygen species, decreased viability and increased DNA damage after treatment with
either hydrogen peroxide (H2O2) or irradiation with UVA. We show that Kindlin-1
is required to fully activate ERK signalling after oxidative damage, and that
activation of ERK protects cells from DNA damage following oxidative stress:
inhibition of ERK activation sensitizes Kindlin-1 expressing cells, but not
Kindlin-1 deficient cells to oxidative stress. Finally we demonstrate that the
Kindlin-1 dependent activation of ERK and protection from DNA damage following
oxidative stress depends on the ability of Kindlin-1 to bind integrins. Thus loss
of Kindlin-1 leads to an imbalance in the cellular oxidative state, which renders
Kindlin-1 deficient cells more prone to the effects of ROS generated in response
to oxidative stress. We propose that Kindlin-1 dependent activation of ERK
signalling is a key molecular mechanism that renders KS keratinocytes more
sensitive to oxidative damage and contributes to the increased photosensitivity
in KS patients.
PMID- 28501564
TI - Wntless promotes bladder cancer growth and acts synergistically as a molecular
target in combination with cisplatin.
AB - PURPOSE: To analyze the contribution of Wnt signaling pathway to bladder cancer
growth in order to identify suitable target molecules for therapy. MATERIAL AND
METHODS: Expression of Wnt 2/4/7, LRP5/6, TCF1/2/4, LEF-1, and beta-actin was
detected by reverse transcription polymerase chain reaction in a panel of 9 and
for Wntless (WLS) in 17 bladder cancer cell lines. Protein expression of WLS was
detected in 6 cell lines. Wnt/beta-catenin activity was analyzed using the
TOPflash/FOPflash luciferase reporter assay. Expression level of beta-catenin,
WIF1, Dickkopf proteins (DKK), HSulf-2, sFRP4, and WLS was modulated by
transfecting or infecting cells transiently or stably with respective shRNAs,
siRNAs, or cDNAs. For protein detection, whole cell lysates were applied to
sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by
immunoblots. Effects on cell growth were determined by cell viability assays and
BrdU/APC incorporation/staining. For 3-dimensional tumor growth, the chicken
chorioallantoic membrane model was used. Tumor growth was characterized by
weight. RESULTS: Expression of molecular components and activation of the Wnt
signaling pathway could be detected in all cell lines. Expression level of beta
catenin, WIF1, DKK, WLS, and HSulf-2 influenced Wnt activity. Expression of WLS
was confirmed in 17 cell lines by reverse transcription polymerase chain reaction
and in 6 cell lines by immunoblotting. WLS positively regulates Wnt signaling,
cell proliferation, and tumor growth in vitro and in vivo. These effects could be
reversed by the expression of the Wnt antagonist WIF1 and DKK. Synergistic
activity of cisplatin and WLS inactivation by genetic silencing could be observed
on cell viability. CONCLUSION: The Wnt signaling pathway is ubiquitously
activated in bladder cancer and regulates tumor growth. WLS might be a target
protein for novel therapies in combination with established chemotherapy
regimens.
PMID- 28501565
TI - Prostate zonal anatomy correlates with the detection of prostate cancer on
multiparametric magnetic resonance imaging/ultrasound fusion-targeted biopsy in
patients with a solitary PI-RADS v2-scored lesion.
AB - PURPOSE: To evaluate the positive predictive value (PPV) of the Prostate Imaging
Reporting and Data System version 2 (PI-RADS v2) assessment method in patients
with a single suspicious finding on prostate multiparametric magnetic resonance
imaging (mpMRI). PATIENTS AND METHODS: A total of 176 patients underwent
MRI/ultrasound fusion-targeted prostate biopsy after the detection of a single
suspicious finding on mpMRI. The PPV for cancer detection was determined based on
PI-RADS v2 assessment score and location. RESULTS: Fusion biopsy detected
prostate cancer in 60.2% of patients. Of these patients, 69.8% had Gleason score
(GS) >=7 prostate cancer. Targeted biopsy detected 90.5% of all GS>=7 prostate
cancer. The PPV for GS>=7 detection of PI-RADS v2 category 5 (P5) and category 4
(P4) lesions was 70.2% and 37.7%, respectively. This increased to 88% and 38.5%
for P5 and P4 lesions in the peripheral zone (PZ), respectively. Targeted biopsy
did not miss GS>=7 disease compared with systematic biopsy in P5 lesions in the
PZ and transition zone. CONCLUSION: The PPV of PI-RADS v2 for prostate cancer in
patients with a single lesion on mpMRI is dependent on PI-RADS assessment
category and location. The highest PPV was for a P5 lesion in the PZ.
PMID- 28501567
TI - Depletion of Jmjd1c impairs adipogenesis in murine 3T3-L1 cells.
AB - Differentiation of adipocytes is a highly regulated process modulated by multiple
transcriptional co-activators and co-repressors. JMJD1C belongs to the family of
jumonji C (jmjC) domain-containing histone demethylases and was originally
described as a ligand-dependent co-activator of thyroid hormone and androgen
receptors. Here, we explored the potential role of Jmjd1c in white adipocyte
differentiation. To investigate the relevance of Jmjd1c in adipogenesis, murine
3T3-L1 preadipocyte cells with transient knock-down of Jmjd1c (3T3_Jmjd1c) were
generated. Depletion of Jmjd1c led to the formation of smaller lipid droplets,
reduced accumulation of triglycerides and maintenance of a more fibroblast-like
morphology after adipocyte differentiation. Concomitantly, insulin stimulated
uptake of glucose and fatty acids was significantly reduced in 3T3_Jmjd1c
adipocytes. In line with these observations we detected lower expression of key
genes associated with lipid droplet formation (Plin1, Plin4, Cidea) and uptake of
glucose and fatty acids (Glut4, Fatp1, Fatp4, Aqp7) respectively. Finally, we
demonstrate that depletion of Jmjd1c interferes with mitotic clonal expansion
(MCE), increases levels of H3K9me2 (dimethylation of lysine 9 of histone H3) at
promotor regions of adipogenic transcription factors (C/EBPs and PPARgamma) and
leads to reduced induction of these key regulators. In conclusion, we have
identified Jmjd1c as a modulator of adipogenesis. Our data suggest that Jmjd1c
may participate in MCE and the activation of the adipogenic transcription program
during the induction phase of adipocyte differentiation in 3T3-L1 cells.
PMID- 28501568
TI - Polytrauma-induced hepatic stress response and the development of liver insulin
resistance.
AB - Insulin resistance and metabolic dysfunction are common following injury.
Polytrauma is defined as combined injuries to more than one body part or organ
system, and is common in modern warfare, as well as automobile and industrial
accidents. Polytrauma can include any combination of burn injury, fracture,
hemorrhage, trauma to the extremities, and blunt or penetrating trauma. Multiple
minor injuries are often more deleterious than a more severe single injury. To
investigate the mechanisms of development of insulin resistance following injury,
we have developed a rat model of polytrauma which combined soft tissue trauma
with burn injury and penetrating gastrointestinal (GI) trauma. Male Sprague
Dawley rats were subjected to a laparotomy plus either a 15-18% total body
surface area scald burn or a single puncture of the cecum (CLP) with a G30
needle, or the combination of both burn and CLP injuries (polytrauma). We
examined the effects of polytrauma which increased markers of hepatic endoplasmic
reticulum (ER) stress, and increased hepatic Trib3 mRNA levels coincident with
reduced insulin-inducible insulin signaling. Phosphorylation/activation of the
insulin receptor (IR) and AKT were decreased at 24, but not 6h following
polytrauma. These results demonstrate a complex, time-dependent development of
hepatic ER-stress and a diminished response to insulin, which were among the
pathological sequelae following polytrauma.
PMID- 28501570
TI - Electrocatalytic properties of N-doped graphite felt in electro-Fenton process
and degradation mechanism of levofloxacin.
AB - The degradation of antibiotic levofloxacin was investigated by dimensionally
stable anode as well as modified cathode using low-cost chemical reagents of
hydrazine hydrate and ethanol for electro-Fenton in an undivided cell at pH 3.0
under room temperature. Comparison of unmodified and modified cathode was
performed. The apparent rate constant of levofloxacin decay was found to be
0.2883 min-1 for graphite felt-10 with the best performance at 200 mA, which is
lower than graphite felt at 400 mA. The optimum modified cathode showed a
significant improvement of complete mineralization of levofloxacin, reaching a
92% TOC removal at 200 mA for 480 min higher than unmodified one at twice the
current. Surface physicochemical properties and morphology were investigated by
scanning electron microscope, contact angle and X-ray photoelectron spectroscopy.
The electrochemical characterization of hydrogen evolution reaction was adopted
to clarify a possible pathway for the higher mineralization of levofloxacin,
indicating a potential pilot-scale study to the pollution with the similar
structure.
PMID- 28501566
TI - DNA methylation regulated gene expression in organ fibrosis.
AB - DNA methylation is a major epigenetic mechanism to regulate gene expression.
Epigenetic regulation, including DNA methylation, histone modifications and RNA
interference, results in heritable changes in gene expression independent of
alterations in DNA sequence. Epigenetic regulation often occurs in response to
aging and environment stimuli, including exposures and diet. Studies have shown
that DNA methylation is critical in the pathogenesis of fibrosis involving
multiple organ systems, contributing to significant morbidity and mortality.
Aberrant DNA methylation can silence or activate gene expression patterns that
drive the fibrosis process. Fibrosis is a pathological wound healing process in
response to chronic injury. It is characterized by excessive extracellular matrix
production and accumulation, which eventually affects organ architecture and
results in organ failure. Fibrosis can affect a wide range of organs, including
the heart and lungs, and have limited therapeutic options. DNA methylation, like
other epigenetic process, is reversible, therefore regarded as attractive
therapeutic interventions. Although epigenetic mechanisms are highly interactive
and often reinforcing, this review discusses DNA methylation-dependent mechanisms
in the pathogenesis of organ fibrosis, with focus on cardiac and pulmonary
fibrosis. We discuss specific pro- and anti-fibrotic genes and pathways regulated
by DNA methylation in organ fibrosis; we further highlight the potential benefits
and side-effects of epigenetic therapies in fibrotic disorders.
PMID- 28501571
TI - Enhanced biodegradation of PAHs in historically contaminated soil by M. gilvum
inoculated biochar.
AB - The inoculation of rice straw biochar with PAH-degrading Mycobacterium gilvum
(1.27 * 1011 +/- 1.24 * 1010 cell g-1), and the subsequent amendment of this
composite material to PAHs contaminated (677 mg kg-1) coke plant soil, was
conducted in order to investigate if would enhance PAHs biodegradation in soils.
The microbe-biochar composite showed superior degradation capacity for
phenanthrene, fluoranthene and pyrene. Phenanthrene loss in the microbe-biochar
composite, free cell alone and biochar alone treatments was, respectively, 62.6
+/- 3.2%, 47.3 +/- 4.1% and non-significant (P > 0.05); whereas for fluoranthene
loss it was 52.1 +/- 2.3%; non-significant (P > 0.05) and non-significant (P >
0.05); and for pyrene loss it was 62.1 +/- 0.9%; 19.7 +/- 6.5% and 13.5 +/- 2.8%.
It was hypothesized that the improved remediation was underpinned by i) biochar
enhanced mass transfer of PAHs from the soil to the carbonaceous biochar "sink",
and ii) the subsequent degradation of the PAHs by the immobilized M. gilvum. To
test this mechanism, a surfactant (Brij 30; 20 mg g-1 soil), was added to impede
PAHs mass transfer to biochar and sorption. The surfactant increased solution
phase PAH concentrations and significantly (P < 0.05) reduced PAH degradation in
the biochar immobilized M. gilvum treatments; indicating the enhanced degradation
occurred between the immobilized M. gilvum and biochar sorbed PAHs.
PMID- 28501569
TI - Influence of sulfur on the accumulation of mercury in rice plant (Oryza sativa
L.) growing in mercury contaminated soils.
AB - Sulfur (S) is an essential element for plant growth and its biogeochemical
cycling is strongly linked to the species of heavy metals in soil. In this work,
the effects of S (sulfate and elemental sulfur) treatment on the accumulation,
distribution and chemical forms of Hg in rice growing in Hg contaminated soil
were investigated. It was found that S could promote the formation of iron plaque
on the root surface and decrease total mercury (T-Hg) and methylmercury (MeHg)
accumulation in rice grains, straw, and roots. Hg in the root was dominated in
the form of RS-Hg-SR. Sulfate treatment increased the percentage of RS-Hg-SR to T
Hg in the rice root and changed the Hg species in soil. The dominant Hg species
(70%) in soil was organic substance bound fractions. Sulfur treatment decreased
Hg motility in the rhizosphere soils by promoting the conversion of RS-Hg-SR to
HgS. This study is significant since it suggests that low dose sulfur treatment
in Hg-containing water irrigated soil can decrease both T-Hg and MeHg
accumulation in rice via inactivating Hg in the soil and promoting the formation
of iron plaque in rice root, which may reduce health risk for people consuming
those crops.
PMID- 28501573
TI - Alterations of DNA methylation in parathyroid tumors.
AB - Parathyroid tumors are common endocrine neoplasias associated with primary
hyperparathyroidism, a metabolic disorder characterized by parathormone
hypersecretion. Parathyroid neoplasia are frequently benign adenomas or multiple
glands hyperplasia, while malignancies are rare. The epigenetic scenario in
parathyroid tumors has just begun to be decoded: DNA methylation, histones and
chromatin modifiers expression have been investigated so far. The main findings
suggest that DNA methylation and chromatin remodeling are active and deregulated
in parathyroid tumors, cooperating with genetic alterations to drive the tumor
phenotype: the tumor suppressors menin and parafibromin, involved in parathyroid
tumorigenesis, interact with chromatin modifiers, defining distinct epigenetic
derangements. Many epigenetic alterations identified in parathyroid tumors are
common to those in human cancers; moreover, some aspects of the epigenetic
profile resemble epigenetic features of embryonic stem cells. Epigenetic profile
may contribute to define the heterogeneity of parathyroid tumors and to provide
targets for new therapeutic approaches.
PMID- 28501572
TI - Quercetin inhibited epithelial mesenchymal transition in diabetic rats, high
glucose-cultured lens, and SRA01/04 cells through transforming growth factor
beta2/phosphoinositide 3-kinase/Akt pathway.
AB - Diabetic cataract (DC), an identified life-threatening secondary complication of
diabetes mellitus, has proven to be a dilemma because of its multifactorial
caused and progression. An increasing number of studies have shown that in
addition to the maillard reaction, enhanced polyol pathway, and oxidative
insults, epithelial mesenchymal transition (EMT) is related to the prevalence of
DC. Quercetin, a classic flavonoid with multiple pharmacological effects has been
reported to possess therapeutic efficacy in the management and treatment of this
disease. However, the mechanism underlying its therapeutic efficacy in EMT of
lens epithelial cells (SRA01/04) and contribution to resolving DC remains a
mystery. Therefore, in this study, we investigated the effects of quercetin on
EMT of SRA01/04 and high-glucose (HG)-induced lens opacity accompanied by lens
fibrosis induced by type-1 diabetes. Furthermore, we sought to clarify the
specific mechanisms underlying these effects. At week 14 after streptozotocin
(STZ) intraperitoneal administration, diabetic rats showed lens opacity
accompanied with diminished antioxidant function, enhanced polyol pathway
activity, and non-enzymatic glycation. Western blotting confirmed EMT in rat
SRA01/04 cells with significantly increased alpha-smooth muscle actin (alpha-SMA)
and decreased E-cadherin expressions. Treatment of the lens with quercetin
ameliorated the oxidative stress, inhibited aldose reductase (AR) activation,
reduced advanced glycation end product (AGE) production, and finally suppressed
EMT in the early stages. Our in vitro results showed that high-glucose activated
the transforming growth factor-beta2/phosphoinositide 3-kinase/protein kinase B
(TGF-beta2/PI3K/Akt) signalling and EMT in SRA01/04 cells. Further, induced
oxidative stress, activation of aldose reductase, and accumulation of advanced
glycation end products were also involved in this process. Quercetin was potent
enough to effectively ameliorate the high glucose (HG)-induced EMT of SRA01/04
cells by inhibiting the activation of TGF-beta2/PI3K/Akt, enhancing the
antioxidant capacity, inhibiting AR activity, and reducing AGE production. From
the whole animal to tissues, and finally the cellular level, our results provide
considerable evidence of the therapeutic potential of quercetin for DC. This
might be due to its inhibition of EMT mediated through inhibition of the TGF
beta/PI3K/Akt pathway.
PMID- 28501574
TI - Androgen production in pediatric adrenocortical tumors may occur via both the
classic and/or the alternative backdoor pathway.
AB - Children with adrenocortical tumors (ACTs) often present with virilization due to
high tumoral androgen production, with dihydrotestosterone (DHT) as most potent
androgen. Recent work revealed two pathways for DHT biosynthesis, the classic and
the backdoor pathway. Usage of alternate routes for DHT production has been
reported in castration-resistant prostate cancer, CAH and PCOS. To assess whether
the backdoor pathway may contribute to the virilization of pediatric ACTs, we
investigated seven children suffering from androgen producing tumors using
steroid profiling and immunohistochemical expression studies. All cases produced
large amounts of androgens of the classic and/or backdoor pathway. Variable
expression of steroid enzymes was observed in carcinomas and adenomas. We found
no discriminative pattern. This suggests that enhanced androgen production in
pediatric ACTs is the result of deregulated steroidogenesis through multiple
steroid pathways. Thus future treatments of ACTs targeting androgen
overproduction should consider these novel steroid production pathways.
PMID- 28501575
TI - The anti-asthmatic drug pranlukast suppresses the delayed-phase vomiting and
reverses intracellular indices of emesis evoked by cisplatin in the least shrew
(Cryptotis parva).
AB - The introduction of second generation serotonin 5-HT3 receptor (5-HT3) antagonist
palonosetron combined with long-acting substance P neurokinin NK1 receptor (NK1)
antagonists (e.g. netupitant) has substantially improved antiemetic therapy
against early- and delayed-phases of emesis caused by highly emetogenic
chemotherapeutics such as cisplatin. However, the improved efficacy comes at a
cost that many patients cannot afford. We introduce a new class of antiemetic,
the antiasthmatic leukotriene CysLT1 receptor antagonist pranlukast for the
suppression of cisplatin-evoked vomiting. Pranlukast (10mg/kg) by itself
significantly reduced the mean frequency of vomits (70%) and fully protected
least shrews from vomiting (46%) during the delayed-phase of cisplatin (10mg/kg)
evoked vomiting. Although, pranlukast tended to substantially reduce both the
mean frequency of vomits and the number of shrews vomiting during the early
phase, these reductions failed to attain significance. When combined with a first
(tropisetron)- or a second (palonosetron)-generation 5-HT3 receptor antagonist,
pranlukast potentiated their antiemetic efficacy during both phases of vomiting.
In addition, pranlukast by itself prevented several intracellular signal markers
of cisplatin-evoked delayed-vomiting such as phosphorylation of ERK1/2 and PKA.
When pranlukast was combined with either palonosetron or tropisetron, these
combinations suppressed the evoked phosphorylation of: i) ERK1/2 during both
acute- and delayed-phase, ii) PKCalpha/beta at the peak acute-phase, and iii) PKA
at the peak delayed-phase. The current and our published findings suggest that
overall behavioral and intracellular signaling effects of pranlukast via blockade
of CysLT1 receptors generally appear to be similar to the NK1 receptor antagonist
netupitant with some differences.
PMID- 28501576
TI - Liraglutide, a glucagon-like peptide-1 analog, induce autophagy and senescence in
HepG2 cells.
AB - It has been reported that glucagon-like peptide-1 (GLP-1) agents have been
associated with both the increased risk of cancer and inhibition of tumor growth
and metastases. The aim of this study is to evaluate the effect of liraglutide on
hepatocellular carcinoma cells - HepG2. Cytometry was used to evaluate mechanism
related to decreased cell proliferation. Nuclear staining and morphometric
analysis were also used to verify the process that was taking place after
treatment with liraglutide, and in order to better understand the mechanism, TGF
beta1 was performed. HepG2 cells decreased proliferation after liraglutide
treatment without altering oxidative stress levels. Liraglutide was able to
induce autophagy and senescence through the increase of TGF-beta1 which possibly
explains the growth decrease. We have demonstrated that liraglutide has an
antiproliferative effect in HepG2 cells inducing autophagy and senescence by the
increase of TGF-beta1.
PMID- 28501577
TI - Probucol attenuates lipopolysaccharide-induced leukocyte recruitment and
inflammatory hyperalgesia: effect on NF-kB activation and cytokine production.
AB - Probucol 4,4'- (Isopropylidenedithio)bis(2,6-di-tert-butylphenol) is a synthetic
molecule clinically used for prevention and treatment of hypercholesterolemia and
atherosclerosis. Recent studies have shown that the beneficial effects of
probucol mainly derive from its anti-inflammatory and antioxidant properties.
Gram-negative bacteria are common infectious agents and their wall components,
e.g. lipopolysaccharide (LPS), are important elicitors of inflammation. LPS is
sensed by tissue resident cells and it triggers a Toll-like receptor 4/MyD88
dependent signaling cascade resulting in endothelial activation, leukocyte
recruitment and nociception. Therefore the present study aimed to investigate the
anti-inflammatory and analgesic effects of probucol in models of LPS-induced
acute inflammation. Probucol at 0.3-30mg/kg was administrated to male Swiss mice
per oral 1h before intraplantar or intraperitoneal lipopolysaccharide stimulus.
Probucol at 3mg/kg reduced lipopolysaccharide-induced mechanical and thermal
hyperalgesia. These effects were accompanied by reduced leukocyte influx and
cytokine production in both paw skin and peritoneum exudate. Unexpectedly,
probucol did not alter lipopolysaccharide-induced tissue oxidative stress at anti
inflammatory /analgesic dose. On the other hand, probucol inhibited
lipopolysaccharide-induced nuclear factor kappa B (NF-kB) activation in paw
tissue as well as NF-kB activity in cultured macrophages in vitro, reinforcing
the inhibitory effect of probucol over the NF-kB signaling pathway. In this
sense, we propose that probucol acts on resident immune cells, such as
macrophages, targeting the NF-kB pathway. As a result, it prevents the
amplification and persistence of the inflammatory response by attenuating NF-kB
dependent cytokine production and leukocyte recruitment explaining its analgesic
effects as well.
PMID- 28501578
TI - Anhydroicaritin, a SREBPs inhibitor, inhibits RANKL-induced osteoclastic
differentiation and improves diabetic osteoporosis in STZ-induced mice.
AB - Nowadays, more and more attention has been paid to osteoporosis caused by
diabetes mellitus. Elevated levels of pro-inflammatory cytokines in diabetic
patients activate the activity of osteoclasts through the RANKL/OPG pathway. The
nuclear transcription factor SREBP2, a master regulator of cholesterol
metabolism, has been found involved in osteoclastogenesis. In our previous study,
we have identified anhydroicaritin as a potent inhibitor of transcription factor
SREBPs, which improves dyslipidemia and insulin resistance. In this study, we
demonstrated that anhydroicaritin could also decrease the level of SREBP2 and its
target genes in osteoclasts induced by RANKL without significant cytotoxicity.
Moreover, anhydroicaritin suppressed RANKL-induced osteoclasts differentiation.
In STZ-induced diabetic mice model, we found that the osteoclasts were largely
increased accompanied with deterioration of bone structure. Anhydroicaritin
decreased the level of blood glucose and alleviated insulin resistance. More
importantly, anhydroicaritin inhibited osteoclast differentiation and rescued
diabetes-induced bone loss in vivo. In conclusion, anhydroicaritin, a potent
SREBP2 inhibitor, inhibits the osteoclasts formation and improves diabetes
induced bone loss.
PMID- 28501579
TI - Eicosapentaenoic acid monoglyceride resolves inflammation in an ex vivo model of
human peripheral blood mononuclear cell.
AB - Phosphorylation and activation of p38 MAPK and NFkappaB pathways, along with the
resulting overproduction of interleukin IL-1beta, IL-6, and tumor necrosis factor
a (TNFalpha) is a hallmark of inflammatory disorders. Omega-3 polyunsaturated
fatty acid (n-3 PUFA) supplementations are known to exert anti-inflammatory
properties by reduction of keys cytokines and enzymes involved in inflammation.
Here, we investigated the anti-inflammatory pathways and mediators modulated by
eicosapentaenoic acid monoglyceride (MAG-EPA) on human peripheral blood
mononuclear cells (PBMCs) from healthy donors and stimulated, ex vivo, with
lipopolysaccharide (LPS). LPS stimulation increased p38 MAPK and NFkappaB
phosphorylation, which was abolished by MAG-EPA treatments. Concomitantly, MAG
EPA also abolished LPS-induced inflammation in PBMCs by reducing IL-1beta, IL-6,
and TNFalpha cytokines at protein and transcript levels. Moreover, MAG-EPA
decreased the levels of HIF1alpha in LPS-induced human PBMCs. Results also
revealed a decreased of pro-inflammatory enzymes such as Cyclooxygenase-2 (COX-2)
and 5-lipoxygenase (5-LOX) in LPS-induced PBMCs. Altogether, the present data
suggest that MAG-EPA, represents a new potential therapeutic strategy for
resolving inflammation in inflammatory disorders including autoimmune diseases,
allergies, asthma, arthritis and cancer.
PMID- 28501580
TI - Can the acute magnetic resonance imaging features reflect neurologic prognosis in
patients with cervical spinal cord injury?
AB - BACKGROUND CONTEXT: Several prognostic studies looked for an association between
the degree of spinal cord injury (SCI), as depicted by primary magnetic resonance
imaging (MRI) within 72 hours of injury, and neurologic outcome. It was not
clearly demonstrated whether the MRI at any time correlates with neurologic
prognosis. PURPOSE: The purpose of the present study was to investigate the
relationship between acute MRI features and neurologic prognosis, especially
walking ability of patients with cervical spinal cord injury (CSCI). Moreover, at
any point, MRI was clearly correlated with the patient's prognosis. STUDY DESIGN:
Retrospective image study. PATIENT SAMPLE: From January 2010 to October 2015, 102
patients with CSCI were treated in our hospital. Patients who were admitted to
our hospital within 3 days after injury were included in this study. The
diagnosis was 78 patients for CSCI with no or minor bony injury and 24 patients
for CSCI with fracture or dislocation. A total of 88 men and 14 women were
recruited, and the mean patient age was 62.6 years (range, 16-86 years).
Paralysis at the time of admission was graded as A in 32, B in 15, C in 42, and D
in 13 patients on the basis of the American Spinal Injury Association (ASIA)
impairment scale. Patients with CSCI with fracture or dislocation were treated
with fixation surgery and those with CSCI with no or minor bony injury were
treated conservatively. Patients were followed up for an average of 168 days
(range, 25-496 days). OUTCOME MEASURES: Neurologic evaluation was performed using
the ASIA motor score and the modified Frankel grade at the time of admission and
discharge. METHODS: Magnetic resonance imaging was performed for all patients at
admission. Using the MRI sagittal images, we measured the vertical diameter of
intramedullary high-intensity changed area with T2-weighted images at the injured
segment. We studied separately the patients divided into two groups: 0-1 day
admission after injury, and 2-3 days admission after injury. We evaluated the
relationship between the vertical diameter of T2 high-intensity changed area in
MR images and neurologic outcome in these two groups. This study does not contain
any conflict of interest. RESULTS: In the group admitted at 0-1 day after injury,
there was a relationship between the vertical diameter of T2 high-intensity area
in MR image and the ASIA motor score at admission and at discharge, but
correlation coefficient was low (0.3766 at admission and 0.4239 at discharge). On
the other hand, in the group admitted at 2-3 days after injury, there was a
significant relationship between the vertical diameter of T2 high-intensity area
in MR image and the ASIA motor score at admission and at discharge, and
correlation coefficient was very high (0.6840 at admission and 0.5293 at
discharge). In the group admitted at 2-3 days after injury, a total of 17
patients (68%) recovered to walk with or without a cane. Receiver operating
characteristic (ROC) curve analysis demonstrated that the optimal vertical
diameter of T2 high-intensity area cutoffvalue for patients who were able to walk
at discharge was 45.8 mm. If the vertical diameter of T2 high-intensity area
cutoff value was 45 mm, there was a significant positive correlation with being
able to walk at discharge (p<.0001). CONCLUSIONS: From our study, 2-3 days after
injury, a significant relationship was observed between the vertical diameter of
T2 high-intensity area and the neurologic prognosis at discharge. Zero to 1 day
after injury, the relationship between the vertical diameter of T2 high-intensity
area and the neurologic prognosis at discharge was weak. Neurologic prognosis is
more correlated with MRI after 2-3 days after the injury. If the vertical
diameter of T2 high-intensity area was <45 mm, the patients were able to walk
with or without a cane at discharge. T2 high-intensity changed area can reflect
the neurologic prognosis in patients with CSCI.
PMID- 28501581
TI - Longer Observation Time Increases Proportion of Neoplasms Detected by
Esophagogastroduodenoscopy.
AB - BACKGROUND & AIMS: Esophagogastroduodenoscopy (EGD) is commonly used to detect
upper gastrointestinal (GI) neoplasms. However, there is little evidence that
longer examination time increases rate of detection of upper GI neoplasia. We
investigated the association between length of time spent performing a normal
screening EGD and rate of neoplasm detection. METHODS: We performed a
retrospective analysis of data from 111,962 subjects who underwent EGD as part of
a comprehensive health-screening program from January 2009 to December 2015 in
Korea. Endoscopy findings were extracted from reports prepared by 14 board
certified endoscopists. Endoscopists were classified as fast or slow based on
their mean examination time for a normal EGD without biopsy during their first
year of the study. All endoscopists used the same endoscopy unit. We obtained
findings from histologic analyses of GI biopsies from patient records; positive
findings were defined as the detection of neoplasms (esophageal, gastric, or
duodenal lesions). We examined the association between examination time and
proportions of neoplasms detected. The primary outcome measure was the rate of
neoplasm detection for each endoscopist (total number of neoplastic lesions
detected divided by the number of subjects screened) and as the proportion of
subjects with at least 1 neoplastic lesion. RESULTS: The mean examination time
was 2 minutes 53 seconds. Using 3 minutes as a cutoff, we classified 8
endoscopists as fast (mean duration, 2:38 +/- 0:21 minutes) and 6 endoscopists as
slow (mean duration, 3:25 +/- 0:19 minutes). Each endoscopist's mean examination
time correlated with their rate of neoplasm detection (R2 = 0.54; P = .046). Fast
endoscopists identified neoplasms in the upper GI tract in 0.20% of patients,
whereas slow endoscopists identified these in 0.28% of patients (P = .0054). The
frequency of endoscopic biopsy varied among endoscopists (range, 6.9%-27.8%) and
correlated with rate of neoplasm detection (R2 = 0.76; P = .0015). On
multivariable analysis, slow endoscopists were more likely to detect gastric
adenomas or carcinomas than fast endoscopists (odds ratio, 1.52; 95% CI, 1.17
1.97). CONCLUSIONS: In a retrospective analysis of data from more than 100,000
subjects who underwent EGD in a screening program, we found slow endoscopists
detected a higher proportion of neoplasms than fast endoscopists. Examination
time is therefore a useful indicator of quality for EGD.
PMID- 28501582
TI - Molecular detection of rifampicin resistance by GeneXpert(r) assay among treated
and untreated pulmonary tuberculosis patients from Khyber Pakhtunkhwa, Pakistan.
AB - OBJECTIVES: Drug-resistant tuberculosis (TB) is an emerging health problem.
Rifampicin (RIF) is the major first-line drug against TB. RIF resistance can be
used as a marker for the detection of multidrug-resistant TB (MDR-TB). The
purpose of this study was to determine the RIF resistance pattern of
Mycobacterium tuberculosis complex isolates among treated and untreated patients
in Khyber Pakhtunkhwa, Pakistan. METHODS: A total of 349 drug-treated and
untreated TB-diagnosed patients were enrolled in this study. RIF resistance was
detected using a GeneXpert(r) assay for amplification of the RIF resistance
determining region (RRDR) region of the rpoB gene. RESULTS: The overall
prevalence of RIF resistance was 5.2% (18/349). Among 49 untreated TB patients, 3
samples (6.1%) were found resistant to RIF. Among 235 patients with a category 1
treatment regimen, 10 samples (4.3%) were resistant to RIF, whilst among 65
patients with a category 2 (Cat-2) treatment regimen, 5 samples (7.7%) were
resistant to RIF. A comparison based on patient sex revealed high RIF resistance
among male compared with female patients. RIF resistance was highest (4/21;
19.0%) in the 21-40 years age group among Cat-2 patients. CONCLUSIONS: The
overall prevalence of RIF resistance was high among treated and untreated TB
patients. These findings will be helpful for better monitoring and management of
RIF resistance in TB patients from Khyber Pakhtunkhwa, Pakistan.
PMID- 28501583
TI - Combining NMR and small angle X-ray scattering for the study of biomolecular
structure and dynamics.
AB - Small-angle X-ray scattering (SAXS) and Nuclear Magnetic Resonance (NMR) are
established methods to analyze the structure and structural transitions of
biological macromolecules in solution. Both methods are directly applicable to
near-native macromolecular solutions and allow one to study structural responses
to physical and chemical changes or ligand additions. Whereas SAXS is applied to
elucidate overall structure, interactions and flexibility over a wide range of
particle sizes, NMR yields atomic resolution detail for moderately sized
macromolecules. NMR is arguably the most powerful technique for the experimental
analysis of dynamics. The joint application of these two highly complementary
techniques provides an extremely useful approach that facilitates comprehensive
characterization of biomacromolecular solutions.
PMID- 28501584
TI - Thiamine potentiates chemoprotective effects of ibuprofen in DEN induced hepatic
cancer via alteration of oxidative stress and inflammatory mechanism.
AB - Present study, was an effort to scrutinize the molecular and biochemical role of
ibuprofen and thiamine combination in diethylnitrosamine (DEN)-induced HCC in
Wistar rats. Single intraperitoneal injection of DEN (200 mg/kg) was used for
induction of HCC in rats. The rats were divided into eight various groups. DEN
induced rats were treated with pure ibuprofen (40 mg/kg) and thiamine in
combination for the period of 12th weeks. The protocol was terminated after the
16th week. Exposure of DEN up-regulated the levels of different serum biochemical
parameters, antioxidant enzyme level, Alfa-fetoprotein (AFP) and reduced the
level of High density lipoprotein (HDL) in Wistar rats along with the alteration
in pro-inflammatory cytokines viz., interlukin-6 (IL-6), Tumor necrosis factor
(TNF-alpha) and Interleukin-1beta (IL-1beta) with decrease in body weight.
Macroscopic evaluation, revealed DEN group rats confirmed the expansion of
hepatic nodules, which were reduced by the individual treatment of ibuprofen and
thiamine, but the synergistic treatment of ibuprofen and thiamine confirm the
significant reduction of hepatic nodules. Further, this combination possesses the
significant chemoprotective effect in DEN-induced HCC by restoring the hepatic
enzymes and other biomarkers along with an alteration in pro-inflammatory
cytokines. The above result concludes that ibuprofen and thiamine combination
possess potent anti-cancerous activity.
PMID- 28501585
TI - Proteolytic Post-Translational Processing of Adhesins in a Pathogenic Bacterium.
AB - Mollicutes, including mycoplasmas and spiroplasmas, have been considered as good
representatives of the " minimal cell " concept: these wall-less bacteria are
small in size and possess a minimal genome and restricted metabolic capacities.
However, the recent discovery of the presence of post-translational modifications
unknown so far, such as the targeted processing of membrane proteins of
mycoplasma pathogens for human and swine, revealed a part of the hidden
complexity of these microorganisms. In this study, we show that in the
phytopathogen, insect-vectored Spiroplasma citri GII-3 adhesion-related protein
(ScARP) adhesins are post-translationally processed through an ATP-dependent
targeted cleavage. The cleavage efficiency could be enhanced in vitro when
decreasing the extracellular pH or upon the addition of polyclonal antibodies
directed against ScARP repeated units, suggesting that modification of the
surface charge and/or ScARP conformational changes could initiate the cleavage.
The two major sites for primary cleavage are localized within predicted
disordered regions and do not fit any previously reported cleavage motif; in
addition, the inhibition profile and the metal ion requirements indicate that
this post-translational modification involves at least one non-conventional
protease. Such a proteolytic process may play a role in S. citri colonization of
cells of the host insect. Furthermore, our work indicates that post-translational
cleavage of adhesins represents a common feature to mollicutes colonizing
distinct hosts and that processing of surface antigens could represent a way to
make the most out of a minimal genome.
PMID- 28501586
TI - Structural Molecular Biology-A Personal Reflection on the Occasion of John
Kendrew's 100th Birthday.
AB - Here, I discuss the development and future of structural molecular biology,
concentrating on the eukaryotic transcription machinery and reflecting on John
Kendrew's legacy from a personal perspective.
PMID- 28501587
TI - Functional Requirements for DjlA- and RraA-Mediated Enhancement of Recombinant
Membrane Protein Production in the Engineered Escherichia coli Strains SuptoxD
and SuptoxR.
AB - In previous work, we have generated the engineered Escherichia coli strains
SuptoxD and SuptoxR, which upon co-expression of the effector genes djlA or rraA,
respectively, are capable of suppressing the cytotoxicity caused by membrane
protein (MP) overexpression and of producing dramatically enhanced yields for a
variety of recombinant MPs of both prokaryotic and eukaryotic origin. Here, we
investigated the functional requirements for DnaJ-like protein A (DjlA)- and
regulator of ribonuclease activity A (RraA)-mediated enhancement of recombinant
MP production in these strains and show that: (i) DjlA and RraA act
independently, that is, the beneficial effects of each protein on recombinant MP
production occur through a mechanism that does not involve the other, and in a
non-additive manner; (ii) full-length and membrane-bound DjlA is required for
exerting its beneficial effects on recombinant MP production in E. coli SuptoxD;
(iii) the MP production-promoting properties of DjlA in SuptoxD involve the
action of the molecular chaperone DnaK but do not rely on the activation of the
regulation of capsular synthesis response, a well-established consequence of djlA
overexpression; (iv) the observed RraA-mediated effects in E. coli SuptoxR
involve the ribonucleolytic activity of RNase E, but not that of its paralogous
ribonuclease RNase G; and (v) DjlA and RraA are unique among similar E. coli
proteins in their ability to promote bacterial recombinant MP production. These
observations provide important clues about the molecular requirements for
suppressed toxicity and enhanced MP accumulation in SuptoxD/SuptoxR and will
guide future studies aiming to decipher the exact mechanism of DjlA- and RraA
mediated enhancement of recombinant MP production in these strains.
PMID- 28501588
TI - Oligomeric Structure of Anabaena Sensory Rhodopsin in a Lipid Bilayer Environment
by Combining Solid-State NMR and Long-range DEER Constraints.
AB - Oligomerization of membrane proteins is common in nature. Here, we combine spin
labeling double electron-electron resonance (DEER) and solid-state NMR (ssNMR)
spectroscopy to refine the structure of an oligomeric integral membrane protein,
Anabaena sensory rhodopsin (ASR), reconstituted in a lipid environment. An
essential feature of such a combined approach is that it provides structural
distance restraints spanning a range of ca 3-60A while using the same sample
preparation (i.e., mutations, paramagnetic labeling, and reconstitution in lipid
bilayers) for both ssNMR and DEER. Direct modeling of the multispin effects on
DEER signal allowed for the determination of the oligomeric order and for
obtaining long-range DEER distance restraints between the ASR trimer subunits
that were used to refine the ssNMR structure of ASR. The improved structure of
the ASR trimer revealed a more compact packing of helices and side chains at the
intermonomer interface, compared to the structure determined using the ssNMR data
alone. The extent of the refinement is significant when compared with typical
helix movements observed for the active states of homologous proteins. Our
combined approach of using complementary DEER and NMR measurements for the
determination of oligomeric structures would be widely applicable to membrane
proteins where paramagnetic tags can be introduced. Such a method could be used
to study the effects of the lipid membrane composition on protein oligomerization
and to observe structural changes in protein oligomers upon drug, substrate, and
co-factor binding.
PMID- 28501590
TI - Are we ready to take ECPR on the road? Maybe....
PMID- 28501591
TI - What you ask for is what you get: A practical approach for early cognitive
screening and the potential for individualized support after cardiac arrest.
PMID- 28501589
TI - Genetic modifiers of multiple sclerosis progression, severity and onset.
AB - The genetic contribution to clinical outcomes for multiple sclerosis (MS) has yet
to be defined. We performed exome sequencing analysis in 100 MS patients
presenting opposite extremes of clinical phenotype (discovery cohort), and
genotyped variants of interest in 2016 MS patients (replication cohort). Linear
and logistic regression analyses were used to identify significant associations
with disease course, severity and onset. Our analysis of the discovery cohort
nominated 38 variants in 21 genes. Replication analysis identified PSMG4 p.W99R
and NLRP5 p.M459I to be associated with disease severity (p=0.002 and 0.008).
CACNA1H p.R1871Q was found associated with patients presenting relapsing
remitting MS at clinical onset (p=0.028) whereas NLRP5 p.M459I and EIF2AK1
p.K558R were associated with primary progressive disease (p=0.031 and 0.023). In
addition, PSMG4 p.W99R and NLRP5 p.R761L were found to correlate with an earlier
age at MS clinical onset, and MC1R p.R160W with delayed onset of clinical
symptoms (p=0.010-0.041).
PMID- 28501592
TI - Endoscopic and molecular characterization of colorectal sessile serrated
adenoma/polyps with cytologic dysplasia.
AB - BACKGROUND AND AIMS: Sessile serrated adenoma/polyps (SSA/Ps), which are
precursor lesions of colorectal cancer (CRC) with BRAF mutation and the CpG
island methylator phenotype (CIMP), develop cytologic dysplasia (CD) during the
progression of colorectal tumorigenesis. In the present study we aimed to clarify
the endoscopic and molecular signatures of SSA/Ps, with and without CD. METHODS:
A series of 208 serrated lesions, including 41 hyperplastic polyps, 90 SSA/Ps, 33
SSA/Ps with CD, and 44 traditional serrated adenomas, were observed and resected
using magnifying endoscopy. BRAF and KRAS mutations and methylation of CIMP
markers (MINT1, MINT2, MINT12, MINT31, and p16) were analyzed through
pyrosequencing. Molecular alterations were then compared with endoscopic and
pathologic characteristics. RESULTS: Among SSA/Ps without CD, the Type II-Open
pit pattern (Type II-O), BRAF mutation, and CIMP were tightly associated with a
proximal colon location. SSA/Ps in the distal colon infrequently exhibited Type
II-O and CIMP. By contrast, most SSA/Ps with CD showed Type II-O plus adenomatous
pit patterns (Type III or IV), BRAF mutation, and CIMP, irrespective of their
locations. CONCLUSIONS: Our results suggest that the Type II-O plus III/IV pit
pattern is a common feature of SSA/Ps with CD in both the proximal and distal
colon and that this pit pattern is a hallmark of serrated lesions at high risk of
developing into CRCs.
PMID- 28501593
TI - Transmural ablation of the normal porcine common bile duct with catheter-directed
irreversible electroporation is feasible and does not affect duct patency.
AB - BACKGROUND AND AIMS: The aim of this study was to evaluate the feasibility and
early safety of catheter-directed irreversible electroporation (IRE) of the
normal common bile duct (CBD) in swine. METHODS: IRE (2000 V, 90 pulses, 100 MUs
pulse) was performed in the CBD of 6 Yorkshire pigs using a catheter electrode
under endoscopic guidance. Ductal patency was assessed with immediate retrograde
cholangiography and contrast-enhanced CT imaging at 1 or 7 days after treatment.
Animals were killed at either 1 day (n = 4, 2 ablations/animal) or 7 days (n = 2,
1 ablation/animal) after treatment. The biliary tract was extracted en bloc and
the length of the ablation along the CBD mucosa was measured. The depth of
ablation was quantified using cross-sections of the treated CBD wall stained with
hematoxylin and eosin. Single-sample hypothesis testing was performed to verify
whether the depth of ablation in the CBD was a representative outcome of IRE
treatment. RESULTS: IRE of the CBD did not result in perforation or obstruction
of the organ at 1 or 7 days after treatment. The length of ablation along the CBD
mucosa was 17.27 +/- 5.55 mm on day 1 samples, and transmural ablation of the CBD
wall was a representative outcome of the treatment (7/8 samples, P < .05). Day 1
samples demonstrated loss of epithelium, transmural necrosis, with preservation
of lumen integrity. Day 7 samples demonstrated re-epithelialization, with diffuse
transmural fibrosis of the CBD wall. These findings were absent from sham tissue
samples. CONCLUSIONS: Intraluminal catheter-directed IRE is feasible and safe for
full-thickness ablation of the normal porcine CBD without affecting lumen patency
up to 1 week after treatment.
PMID- 28501594
TI - The SAFE-T assessment tool: derivation and validation of a web-based application
for point-of-care evaluation of gastroenterology fellow performance in
colonoscopy.
AB - BACKGROUND AND AIMS: Attending assessment is a critical part of endoscopic
education for gastroenterology fellows. The aim of this study was to develop and
validate a concise assessment tool to evaluate real-time fellow performance in
colonoscopy administered via a web-based application. METHODS: The Skill
Assessment in Fellow Endoscopy Training (SAFE-T) tool was derived as a novel 5
question evaluation tool that captures both summative and formative feedback
adapted into a web-based application. A prospective study of 15 gastroenterology
fellows (5 fellows each from years 1 to 3 of training) was performed using the
SAFE-T tool. An independent reviewer evaluated a subset of these procedures and
completed the SAFE-T tool and Mayo Colonoscopy Skills Assessment Tool (MCSAT) for
reliability testing. RESULTS: Twenty-six faculty completed 350 SAFE-T evaluations
of the 15 fellows in the study. The mean SAFE-T overall score (year 1, 2.00; year
2, 3.84; year 3, 4.28) differentiated each sequential fellow year of training (P
< .0001). The mean SAFE-T overall score decreased with increasing case complexity
score, with straightforward cases compared with average cases (4.07 vs 3.50, P <
.0001), and average cases compared with challenging cases (3.50 vs 3.08, P =
.0134). In dual-observed procedures, the SAFE-T tool showed excellent inter-rater
reliability with a kappa agreement statistic of 0.898 (P < .0001). Correlation of
the SAFE-T overall score with the MCSAT overall hands-on and individual motor
scores was excellent (each r > 0.90, P < .0001). CONCLUSIONS: We developed and
validated the SAFE-T assessment tool, a concise and web-based means of assessing
real-time gastroenterology fellow performance in colonoscopy.
PMID- 28501596
TI - A novel FbFP-based biosensor toolbox for sensitive in vivo determination of
intracellular pH.
AB - The intracellular pH is an important modulator of various bio(techno)logical
processes such as enzymatic conversion of metabolites or transport across the
cell membrane. Changes of intracellular pH due to altered proton distribution can
thus cause dysfunction of cellular processes. Consequently, accurate monitoring
of intracellular pH allows elucidating the pH-dependency of (patho)physiological
and biotechnological processes. In this context, genetically encoded biosensors
represent a powerful tool to determine intracellular pH values non-invasively and
with high spatiotemporal resolution. We have constructed a toolbox of novel
genetically encoded FRET-based pH biosensors (named Fluorescence Biosensors for
pH or FluBpH) that utilizes the FMN-binding fluorescent protein EcFbFP as donor
domain. In contrast to many fluorescent proteins of the GFP family, EcFbFP
exhibits a remarkable tolerance towards acidic pH (pKa~3.2). To cover the broad
range of physiologically relevant pH values, three EYFP variants exhibiting pKa
values of 5.7, 6.1 and 7.5 were used as pH-sensing FRET acceptor domains. The
resulting biosensors FluBpH 5.7, FluBpH 6.1 and FluBpH 7.5 were calibrated in
vitro and in vivo to accurately evaluate their pH indicator properties. To
demonstrate the in vivo applicability of FluBpH, changes of intracellular pH were
ratiometrically measured in E. coli cells during acid stress.
PMID- 28501597
TI - Reciprocal regulation between hepcidin and erythropoiesis and its therapeutic
application in erythroid disorders.
AB - Iron is required for hemoglobin production, and it plays a key role during
erythropoiesis. Systemic iron homeostasis is mainly negatively regulated by the
peptide hormone hepcidin, coded by the gene HAMP. Hepcidin excess may cause iron
deficiency, iron-restricted erythropoiesis, and anemia. Conversely, hepcidin
insufficiency leads to iron overload and oxidative damage in multiple tissues.
During regulation of hepcidin synthesis, multiple promoter elements in the HAMP
gene respond to variable signaling pathways corresponding to different
extracellular situations. It has been reported that hepcidin expression can be
suppressed by secreted erythroid factors, including GDF15, TWSG1, GDF11, and
ERFE, thereby increasing iron availability for hemoglobin synthesis. These
potential erythroid factors act via intricate mechanisms that remain
controversial. However, it is clear that hepcidin affects erythropoiesis, and
promising therapies targeting hepcidin have been developed to treat erythroid
disorders. These therapeutic strategies include suppressing or activating HAMP
gene expression, mimicking or activating hepcidin activity, and blocking the
ability of hepcidin to bind to its target ferroportin.
PMID- 28501595
TI - Corticolimbic circuitry in the modulation of chronic pain and substance abuse.
AB - The transition from acute to chronic pain is accompanied by increased engagement
of emotional and motivational circuits. Adaptations within this corticolimbic
circuitry contribute to the cellular and behavioral maladaptations associated
with chronic pain. Central regions within the corticolimbic brain include the
mesolimbic dopamine system, the amygdala, and the medial prefrontal cortex. The
evidence reviewed herein supports the notion that chronic pain induces
significant changes within these corticolimbic regions that contribute to the
chronicity and intractability of pain. In addition, pain-induced changes in
corticolimbic circuitry are poised to impact motivated behavior and reward
responsiveness to environmental stimuli, and may modulate the addiction liability
of drugs of abuse, such as opioids.
PMID- 28501598
TI - Microgramma vacciniifolia (Polypodiaceae) fronds contain a multifunctional lectin
with immunomodulatory properties on human cells.
AB - In this study, we report the purification and characterization of a
multifunctional lectin (MvFL) from Microgramma vacciniifolia fronds as well as
its immunomodulatory properties on human peripheral blood mononuclear cells
(PBMCs). MvFL (pI 4.51; 54kDa) is a glycoprotein able to inhibit trypsin activity
and that has sequence similarities (32% coverage) with a plant RNA-binding
protein. Hemagglutinating activity of MvFL was not altered by heating at 100
degrees C for 30min, but was reduced in alkaline pH (8.0 and 9.0). Fluorimetric
analyses showed that this lectin did not undergo marked conformational changes
when heated. However, the MvFL conformation changed depending on the pH. MvFL at
6.25-25MUg/mL was not cytotoxic to lymphocytes present among PBMCs. The PBMCs
incubated for 24h with the lectin (12.5MUg/mL) showed increased TNF-alpha, IFN
gamma, IL-6, IL-10, and nitric oxide production. MvFL also stimulated T
lymphocytes from PBMCs to differentiate into CD8+ cells. The activation
(indicated by CD28 expression) of these cells was also stimulated. In conclusion,
MvFL is a heat-stable and multifunctional protein, with both lectin and trypsin
inhibitor activities, and capable of inducing predominantly a Th1 response in
human PBMCs as well as activation and differentiation of T lymphocytes.
PMID- 28501599
TI - pH induced single step shift of hydrophobic patches followed by formation of an
MG state and an amyloidogenic intermediate in Lima Bean Trypsin Inhibitor (LBTI).
AB - Lima Bean Trypsin Inhibitor (LBTI) is 83 residues monomeric protein of 9.0 KDa,
consisting of six antiparallel beta-strands and can undergo concentration
dependant dimerization. We have tried to characterize folding intermediates of
LBTI under equilibrium denaturation conditions. We have used various
spectroscopic and microscopic techniques to understand the folding and misfolding
pathways. LBTI forms molten globule structure at pH 2 and amyloidiogenic
intermediate state (Ia) at pH 4. pH induced Shifting of surface exposed
hydrophobic patches and that followed by withdrawal of the lone tyrosine residue
(Y69) towards nonpolar environment have been reported. Denaturation profile of
native and molten globule (MG) states of LBTI in presence of guanidine
hydrochloride show sigmoidal curves with non-coincidental and irreversible
behaviour in both states. Concentration dependent amyloid fibril formation was
confirmed by Thioflavin T and Congo Red binding and its morphology was studied by
transmission electron microscopy (TEM). This is the first report on biophysical
characterization of folding intermediates of LBTI and its aggregation behaviour
to the best of our knowledge.
PMID- 28501600
TI - Development of a human epidermal growth factor derivative with EGFR-blocking and
depleted biological activities: A comparative in vitro study using EGFR-positive
breast cancer cells.
AB - Epidermal growth factor (EGF) is a local growth factor that stimulates cell
growth, proliferation, and differentiation by binding to its receptor EGFR. EGF
and EGFR are involved in many aspects of the development of carcinomas. Because
EGFR has been found to be over-expressed in many tumors of epithelial origin, it
is a potential target for antitumor therapy. In this study we designed a mutated
form of hEGF (mEGF) with a deletion of four amino acids residues (Gln43, Tyr44,
Arg45 and Asp46) in order to show importance of Leu spatial location for EGFR
binding/activation. Expression vector pET32a+ and E. Coli, strain Rosetta-gami B
(DE3) were used to enhance solubility of the recombinant protein with yielding
approximately 10mg/l of cell culture. The purified cleaved hEGF as well as non
cleaved fusion protein were biologically active, which was confirmed by their
equal ability to stimulate proliferation of MCF7 cells. The mEGF showed
specificity and high affinity for EGFR binding, however binding affinity of mEGF
for EGFR was reduced about 11.5 fold compared with that of hEGF. The mEGF effect
on the MCF7 cell proliferation had a relatively different outcome; mEGF simulated
differential cell growth in a dose dependent manner. On the other hand, in MDA
MB468 cells, hEGF and mEGF induced growth inhibition, which was much more severe
for hEGF than that of mEGF. Also, hEGF strongly induced the phosphorylation of
EGF receptor in MDA-MB468 cells while mEGF induced poor EGFR phosphorylation. The
same observations were also made for migration of cancer cells, especially
induction of MDA-MB468 migration by mEGF was significantly lower than that of
hEGF, suggesting a connection between tyrosine phosphorylation of EGFR and cell
migration. Docking analysis revealed that the binding affinity and the buried
surface area of mEGF to EGFR complex are lower than those of hEGF/EGFR. Although
theoretical studies confirmed reduction in mEGF-EGFR binding affinity, the data
of the present study indicate that mEGF is a potential EGFR blocker but may
highlight it as excellent delivery agent of protein/non-protein toxins as well as
for alpha-, beta-, gamma-emitting radio-immunotherapy.
PMID- 28501601
TI - Novel inhibitors of tyrosinase produced by the 4-substitution of TCT (P).
AB - Novel Tyrosinase Inhibitors of 4-functionalized Thiophene-2-carbaldehyde
thiosemicarbazone (TCT) derivatives (1-8) had been synthesized and
Spectrofluorimetry, 1H and 13C NMR titration and Molecular docking had been used
to investigate their inhibitory activities and mechanisms on tyrosinase. The
results showed that the inter-molecular interactions or hydrogen bond formation
by increasing length of carbon chain or introducing benzene ring to the 4
functionalized ester group promoted or stabilized formation of complexes between
modifier and tyrosinase, and enhanced the inhibitory activity of modifiers. The
inhibitory activity of 4-benzoy methoxy-TCT was much stronger than that of any
other synthesized tested modifiers, which was well explained by molecular docking
and further verified by spectrofluorimetry and NMR titration by assuming that
there existed an inter-molecular interaction besides formation of hydrogen bonds
between the amino acid residues ASN260, GLU256, HIS85 of enzyme and the
modifier.We concluded that 4-benzoy methoxy substitution of TCT was a good route
obtaining novel tyrosinase inhibitors and deserved further studies.
PMID- 28501602
TI - Soluble epoxide hydrolase inhibitory activity of components from Leonurus
japonicus.
AB - One new compound, 10-methoxy-leonurine (1), and four known compounds (2-5) were
purified by silica gel, C-18, and Sephadex LH-20 column chromatography from
Leonurus japonicus. Their structures were elucidated using one-dimensional
(1D)/two-dimensional (2D)-nuclear magnetic resonance (NMR), high-resolution (HR)
electrospray ionization (ESI) mass spectrometry (MS). The compounds were
evaluated to determine their inhibition of the catalysis of soluble epoxide
hydrolase (sEH). According to the results from in vitro analyses, compounds 1 and
2, which contain guanidine and flavonoid (3), were determined to be potential
inhibitors of this enzyme. All compounds were revealed to be non-competitive
inhibitors according to Lineweaver-Burk plots. Furthermore, in silico molecular
docking indicated that compounds 1-3 are bound to sEH in a similar fashion and
have stable binding energies, as calculated by AutoDock 4.2. Molecular dynamics
determined the root-mean-square deviation (RMSD), total energy, RMS fluctuation
(RMSF), hydrogen bonds, and distance of the complex according to time.
PMID- 28501603
TI - Polyelectrolyte complexes based on alginate/tanfloc: Optimization,
characterization and medical application.
AB - Hydrogels based on alginate and tanfloc (a cationic biopolymer obtained from
natural condensed tannins) were successfully prepared. Tanfloc (TN) presents high
aqueous solubility at pHs lower than 10; it contains substituted amino sites and
molar weight of ca. 600,000gmol-1. A factorial design (22) was used to optimize
the yield of alginate/tanfloc polyelectrolyte complexes (PECs). Dialysis
recovered the overplus of alginate (AG) no complexed with TN. These materials
were characterized by thermal analyses (TGA/DTG and DSC), zeta potential, and
FTIR, while SEM technique depicted a rough surface on AG/TN complex, containing
non-homogeneous pores. Indeed, the AG and TN were tailored to elicit scaffold
materials with outstanding cytocompatibility, mainly upon mouse preosteoblastic
cells because of reconstruction of bone tissues (119% at 10days). The AG/TN
complex also displayed antioxidant and bactericidal activities against
Staphylococcus aureus (S. aureus). Besides, the pristine TN fostered
bacteriostatic and bactericidal performances towards S. aureus and Escherichia
coli. However, for our best knowledge, no studies were still carried out on TN
and TN-based materials for medical purpose.
PMID- 28501604
TI - High production, purification, biochemical characterization and gene analysis of
a novel catalase from the thermophilic bacterium Ureibacillus thermosphaericus
FZSF03.
AB - A catalase-producing thermophilic bacterium, Ureibacillus thermosphaericus
FZSF03, was isolated from high-temperature compost. Catalase production in this
strain increased 31 times and reached 57,630U/mL after optimization in a shake
flask, which might represent the highest catalase activity level among reported
wild strains. This catalase was further purified and identified. The purified
enzyme showed a specific activity of 219,360U/mg, higher than many other
catalases. The molecular weight of this enzyme is 52kDa according to sodium
dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and the enzyme was
identified as a monofunctional haeme catalase of Ureibacillus thermosphaericus by
liquid chromatography-mass spectrometry (LC-MS)/MS. The optimal reaction
temperature for this catalase was found to be 60 degrees C. Stability was
observed at 60 degrees C and at a pH of 10.0, indicating the superiority of this
enzyme at a high temperature and under alkaline conditions. Therefore, this
catalase is a prospective candidate for industrial production and applications.
The gene encoding this catalase is 1503bp. As the amino acid sequence shows low
similarity with other catalases, we suggest that this is a novel monofunctional
haeme catalase.
PMID- 28501606
TI - Diabetes present and future.
PMID- 28501605
TI - The role of multilayers in preventing the premature buckling of the pulmonary
surfactant.
AB - The pulmonary surfactant is a protein-lipid mixture that spreads into a film at
the air-lung interface. The highly-compacted molecules of the film keep the
interface from shrinking under the influence of otherwise high surface tension
and thus prevent atelectasis. We have previously shown that for the film to
withstand a high film pressure without collapsing it needs to assume a specific
architecture of a molecular monolayer with islands of stacks of molecular
multilayers scattered over the area. Surface activity was assessed in a captive
bubble surfactometer (CBS) and the role of cholesterol and oxidation on
surfactant function examined. The surfactant film was conceptualized as a plate
under pressure. Finite element analysis was used to evaluate the role of the
multilayer stacks in preventing buckling of the plate during compression. The
model of film topography was constructed from atomic force microscope (AFM) scans
of surfactant films and known physical properties of
dipalmitoylphosphatidylcholine (DPPC), a major constituent of surfactant, using
ANSYS structural-analysis software. We report that multilayer structures increase
film stability. In simulation studies, the critical load required to induce
surfactant film buckling increased about two-fold in the presence of multilayers.
Our in vitro surfactant studies showed that surface topography varied between
functional and dysfunctional films. However, the critical factor for film
stability was the anchoring of the multilayers. Furthermore, the anchoring of
multilayers and mechanical stability of the film was dependent on the presence of
hydrophobic surfactant protein-C. The current study expands our understanding of
the mechanism of surfactant inactivation in disease.
PMID- 28501607
TI - The association between high levels of cumulative life stress and aberrant
resting state EEG dynamics in old age.
AB - Cumulative experienced stress produces shortcomings in old adults' cognitive
performance. These are reflected in electrophysiological changes tied to task
execution. This study explored whether stress-related aberrations in older
adults' electroencephalographic (EEG) activity were also apparent in the system
at rest. To this effect, the amount of stressful life events experienced by 60
young and 60 elderly participants were assessed in conjunction with resting state
power changes in the delta, theta, alpha, and beta frequencies during a resting
EEG recording. Findings revealed elevated levels of delta power among elderly
individuals reporting high levels of cumulative life stress. These differed
significantly from young high and low stress individuals and old adults with low
levels of stress. Increases of delta activity have been linked to the emergence
of conditions such as Alzheimer's Disease and Mild Cognitive Impairment. Thus, a
potential interpretation of our findings associates large amounts of cumulative
stress with an increased risk of developing age-related cognitive pathologies in
later life.
PMID- 28501608
TI - Porosity of spacer-filled channels in spiral-wound membrane systems:
Quantification methods and impact on hydraulic characterization.
AB - The porosity of spacer-filled feed channels influences the hydrodynamics of
spiral-wound membrane systems and impacts the overall performance of the system.
Therefore, an exact measurement and a detailed understanding of the impact of the
feed channel porosity is required to understand and improve the hydrodynamics of
spiral-wound membrane systems applied for desalination and wastewater reuse. The
objectives of this study were to assess the accuracy of porosity measurement
techniques for feed spacers differing in geometry and thickness and the
consequences of using an inaccurate method on hydrodynamic predictions, which may
affect permeate production. Six techniques were applied to measure the porosity
namely, three volumetric techniques based on spacer strand count together with a
cuboidal (SC), cylindrical (VCC) and ellipsoidal volume calculation (VCE) and
three independent techniques based on volume displacement (VD), weight and
density (WD) and computed tomography (CT) scanning. The CT method was introduced
as an alternative for the other five already existing and applied methods in
practice. Six feed spacers used for the porosity measurement differed in filament
thickness, angle between the filaments and mesh-size. The results of the studies
showed differences between the porosities, measured by the six methods. The
results of the microscopic techniques SC, VCC and VCE deviated significantly from
measurements by VD, WD and CT, which showed similar porosity values for all
spacer types. Depending on the maximum deviation of the porosity measurement
techniques from -6% to +6%, (i) the linear velocity deviations were -5.6% and
+6.4% respectively and (ii) the pressure drop deviations were -31% and +43%
respectively, illustrating the importance of an accurate porosity measurement.
Because of the accuracy and standard deviation, the VD and WD method should be
applied for the porosity determination of spacer-filled channels, while the CT
method is recommended for numerical modelling purposes. The porosity has a linear
relationship with the flow velocity and a superlinear effect on the pressure
drop. Accurate porosity data are essential to evaluate feed spacer performance in
spiral-wound membrane systems. Porosity of spacer-filled feed channels has a
strong impact on membrane performance and biofouling impact.
PMID- 28501609
TI - Return on investment from fuel treatments to reduce severe wildfire and erosion
in a watershed investment program in Colorado.
AB - A small but growing number of watershed investment programs in the western United
States focus on wildfire risk reduction to municipal water supplies. This paper
used return on investment (ROI) analysis to quantify how the amounts and
placement of fuel treatment interventions would reduce sediment loading to the
Strontia Springs Reservoir in the Upper South Platte River watershed southwest of
Denver, Colorado following an extreme fire event. We simulated various extents of
fuel mitigation activities under two placement strategies: (a) a strategic
treatment prioritization map and (b) accessibility. Potential fire behavior was
modeled under each extent and scenario to determine the impact on fire severity,
and this was used to estimate expected change in post-fire erosion due to
treatments. We found a positive ROI after large storm events when fire mitigation
treatments were placed in priority areas with diminishing marginal returns after
treating >50-80% of the forested area. While our ROI results should not be used
prescriptively they do show that, conditional on severe fire occurrence and
precipitation, investments in the Upper South Platte could feasibly lead to
positive financial returns based on the reduced costs of dredging sediment from
the reservoir. While our analysis showed positive ROI focusing only on post-fire
erosion mitigation, it is important to consider multiple benefits in future ROI
calculations and increase monitoring and evaluation of these benefits of wildfire
fuel reduction investments for different site conditions and climates.
PMID- 28501610
TI - Application of doped photocatalysts for organic pollutant degradation - A review.
AB - Advanced oxidation process involves production of hydroxyl radical for industrial
wastewater treatment. This method is based on the irradiation of UV light to
photocatalysts such as TiO2 and ZnO for photodegradation of pollutant. UV light
is used for irradiation in photocatalytic process because TiO2 has a high band
gap energy which is around 3.2 eV. There can be shift adsorption to visible light
by reducing the band gap energy to below 3.2 eV. Doped catalyst is one of the
means to reduce band gap energy. Different methods are used for doped catalyst
which uses transition metals and titanium dioxide. The band gap energy of three
types of transition metals Fe, Cd and Co after being doped with TiO2, are around
2.88 ev, 2.97ev and 2.96 ev, respectively which are all below TiO2 energy. Some
of the transition metals change the energy level to below 3.2 eV and the
adsorption shifts to visible light for degradation of industrial pollutant after
being doped with titanium dioxide. This paper aims at providing a deep insight
into advanced oxidation processes, photocatalysts and their applications in
wastewater treatment, doping processes and the effects of operational factors on
photocatalytic degradation.
PMID- 28501611
TI - Multilocus phylogeny and statistical biogeography clarify the evolutionary
history of major lineages of turtles.
AB - Despite their complex evolutionary history and the rich fossil record, the higher
level phylogeny and historical biogeography of living turtles have not been
investigated in a comprehensive and statistical framework. To tackle these
issues, we assembled a large molecular dataset, maximizing both taxonomic and
gene sampling. As different models provide alternative biogeographical scenarios,
we have explicitly tested such hypotheses in order to reconstruct a robust
biogeographical history of Testudines. We scanned publicly available databases
for nucleotide sequences and composed a dataset comprising 13 loci for 294 living
species of Testudines, which accounts for all living genera and 85% of their
extant species diversity. Phylogenetic relationships and species divergence times
were estimated using a thorough evaluation of fossil information as calibration
priors. We then carried out the analysis of historical biogeography of Testudines
in a fully statistical framework. Our study recovered the first large-scale
phylogeny of turtles with well-supported relationships following the topology
proposed by phylogenomic works. Our dating result consistently indicated that the
origin of the main clades, Pleurodira and Cryptodira, occurred in the early
Jurassic. The phylogenetic and historical biogeographical inferences permitted us
to clarify how geological events affected the evolutionary dynamics of crown
turtles. For instance, our analyses support the hypothesis that the breakup of
Pangaea would have driven the divergence between the cryptodiran and pleurodiran
lineages. The reticulated pattern in the ancestral distribution of the
cryptodiran lineage suggests a complex biogeographic history for the clade, which
was supposedly related to the complex paleogeographic history of Laurasia. On the
other hand, the biogeographical history of Pleurodira indicated a tight
correlation with the paleogeography of the Gondwanan landmasses.
PMID- 28501612
TI - The effects of Pleistocene climate change on biotic differentiation in a montane
songbird clade from Wallacea.
AB - The role of Pleistocene Ice Age in tropical diversification is poorly understood,
especially in archipelagos, in which glaciation-induced sea level fluctuations
may lead to complicated changes in land distribution. To assess how Pleistocene
land bridges may have facilitated gene flow in tropical archipelagos, we
investigated patterns of diversification in the rarely-collected rusty-bellied
fantail Rhipidura teysmanni (Passeriformes: Rhipiduridae) complex from Wallacea
using a combination of bioacoustic traits and whole-genome sequencing methods (dd
RADSeq). We report a biogeographic leapfrog pattern in the vocalizations of these
birds, and uncover deep genomic divergence among island populations despite the
presence of intermittent land connections between some. We demonstrate how rare
instances of genetic introgression have affected the evolution of this species
complex, and document the presence of double introgressive mitochondrial sweeps,
highlighting the dangers of using only mitochondrial DNA in evolutionary
research. By applying different tree inference approaches, we demonstrate how
concatenation methods can give inaccurate results when investigating divergence
in closely-related taxa. Our study highlights high levels of cryptic avian
diversity in poorly-explored Wallacea, elucidates complex patterns of Pleistocene
climate-mediated diversification in an elusive montane songbird, and suggests
that Pleistocene land bridges may have accounted for limited connectivity among
montane Wallacean biota.
PMID- 28501613
TI - Naegleria fowleri infections.
PMID- 28501614
TI - Shaping mitochondrial dynamics: The role of cAMP signalling.
AB - In recent years, our idea of mitochondria evolved from "mere" energy and
metabolite producers to key regulators of many cellular functions. In order to
preserve and protect their functional status, these organelles engage a number of
dynamic processes that allow them to decrease accumulated burden and maintain
their homeostasis. Indeed, mitochondria can unite (fusion), divide (fission),
position themselves strategically in the cell (motility/trafficking) and if
irreversibly damaged or dysfunctional eliminated (mitophagy). These dynamic
processes can be controlled both by mitochondrial and cellular signalling
pathways, hence allowing mitochondria to tune their function to the cellular
needs. Among the regulatory mechanisms, reversible phosphorylation downstream the
cyclic AMP (cAMP) signalling cascade was shown to deeply influence mitochondrial
dynamics. This review explores the emerging evidence suggesting that cAMP is a
key player in the orchestration of mitochondrial fusion/fission, motility and
mitophagy, extending the repertoire of this second messenger, which is now
recognised as a major regulator of mitochondrial homeostasis.
PMID- 28501615
TI - The changes in glucose metabolism and cell proliferation in the kidneys of
polycystic kidney disease mini-pig models.
AB - The pathogenic mechanism of polycystic kidney disease (PKD) is unclear. Abnormal
glucose metabolism is maybe involved in hyper-proliferation of renal cyst
epithelial cells. Mini-pigs are more similar to humans than rodents and
therefore, are an ideal large animal model. In this study, for the first time, we
systematically investigated the changes in glucose metabolism and cell
proliferation signaling pathways in the kidney tissues of chronic progressive PKD
mini-pig models created by knock-outing PKD1gene. The results showed that in the
kidneys of PKD mini-pigs, the glycolysis is increased and the expressions of key
oxidative phosphorylation enzymes Complexes I and IV significantly decreased. The
activities of mitochondrial respiration chain Complexes I and IV significantly
decreased; the phosphorylation level of key metabolism-modulating molecule AMP
activated protein kinase (AMPK) significantly decreased; and the mammalian target
of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) signaling
pathway are activated obviously. This study showed that in the kidneys of PKD
mini-pigs, the level of glycolysis significantly increased, oxidative
phosphorylation significantly decreased, and cell proliferation signaling
pathways significantly activated, suggesting that metabolic changes in PKD may
result in the occurrence and development of PKD through the activation of
proliferation signaling pathways.
PMID- 28501616
TI - Identification of phosphorylation sites on beta1-adrenergic receptor in the mouse
heart.
AB - beta1-adrenergic receptor (Adrb1) belongs to the superfamily of G-protein-coupled
receptors (GPCRs) and plays a critical role in the regulation of heart rate and
myocardial contraction force. GPCRs are phosphorylated at multiple sites to
regulate distinct signal transduction pathways in different tissues. However,
little is known about the location and function of distinct phosphorylation sites
of Adrb1 in vivo. To clarify the mechanisms underlying functional regulation
associated with Adrb1 phosphorylation in vivo, we aimed to identify Adrb1
phosphorylation sites in the mouse heart using phosphoproteomics techniques with
nano-flow liquid chromatography/tandem mass spectrometry (LC-MS/MS). We revealed
the phosphorylation residues of Adrb1 to be Ser274 and Ser280 in the third
intracellular loop and Ser412, Ser417, Ser450, Ser451, and Ser462 at the C
terminus. We also found that phosphorylation at Ser274, Ser280, and Ser462 was
enhanced in response to stimulation with an Adrb1 agonist. This is the first
study to identify Adrb1 phosphorylation sites in vivo. These findings will
provide novel insights into the regulatory mechanisms mediated by Adrb1
phosphorylation.
PMID- 28501617
TI - Biochemical and biophysical characterization of ruthenation of BRCA1 RING protein
by RAPTA complexes and its E3 ubiquitin ligase activity.
AB - RAPTA compounds, ([Ru(eta6-arene)(PTA)Cl2], PTA = 1,3,5-triaza-7
phosphaadamantane), have been reported to overcome drug resistance in cisplatin
resistant cells. However, the exact mechanism of these complexes is still largely
unexplored. In this study, the interaction of some RAPTA compounds with the N
terminal fragment of the BRCA1 RING domain protein was investigated. The binding
of the RAPTA compounds to the BRCA1 protein resulted in a release of Zn2+ ions in
a dose and time dependent manner, as well as thermal alteration of ruthenated
BRCA1 proteins. Electron Transfer Dissociation (ETD) fragmentation mass
spectrometry revealed the preferential binding sites of the RAPTA complexes on
the BRCA1 zinc finger RING domain at a similar short peptide stretch,
Cys24Lys25Phe26Cys27Met28Leu29 and Lys35 (residues 44-49 and 55 on full length
BRCA1). Changes in the conformation and binding constants of ruthenium-BRCA1
adducts were established, resulting in inactivation of the RING heterodimer
BRCA1/BARD1-mediated E3 ubiquitin ligase function. These findings could provide
mechanistic insight into the mode of action of RAPTA complexes for on tested
BRCA1 model protein.
PMID- 28501618
TI - Assessing activity of Hepatitis A virus 3C protease using a cyclized luciferase
based biosensor.
AB - Hepatitis A is an acute infection caused by Hepatitis A virus (HAV), which is
widely distributed throughout the world. The HAV 3C cysteine protease (3Cpro), an
important nonstructural protein, is responsible for most cleavage within the
viral polyprotein and is critical for the processes of viral replication. Our
group has previously demonstrated that HAV 3Cpro cleaves human NF-kappaB
essential modulator (NEMO), a kinase required in interferon signaling. Based on
this finding, we generated four luciferase-based biosensors containing the NEMO
sequence (PVLKAQ?ADIYKA) that is cleaved by HAV 3Cpro and/or the Nostoc
punctiforme DnaE intein, to monitor the activity of HAV 3Cpro in human embryonic
kidney cells (HEK-293T). Western blotting showed that HAV 3Cpro recognized and
cleaved the NEMO cleavage sequence incorporated in the four biosensors, whereas
only one cyclized luciferase-based biosensor (233-DnaE-HAV, 233DH) showed a
measurable and reliable increase in firefly luciferase activity, with very low
background, in the presence of HAV 3Cpro. With this biosensor (233DH), we
monitored HAV 3Cpro activity in HEK-293T cells, and tested it against a
catalytically deficient mutant HAV 3Cpro and other virus-encoded proteases. The
results showed that the activity of this luciferase biosensor is specifically
dependent on HAV 3Cpro. Collectively, our data demonstrate that the luciferase
biosensor developed here might provide a rapid, sensitive, and efficient
evaluation of HAV 3Cpro activity, and should extend our better understanding of
the biological relevance of HAV 3Cpro.
PMID- 28501620
TI - Molecular characterization of Netrin-1 and APP receptor binding: New leads to
block the progression of senile plaques in Alzheimer's disease.
AB - Alzheimer's disease is a growing concern in the context of the increasing
lifespan of the populations. The work presented here is part of the fight against
this threat. It supports a therapeutic approach to reduce the incidence of
Alzheimer's disease, taking advantage of the specific binding of several domains
of Netrin-1 to the beta-amyloid precursor protein. This basic knowledge shall
then be used to predict, design or characterize lead compounds that may in turn
inhibit/delay Alzheimer's disease's progression, extending the therapeutic offer
of the other leads already being investigated in this line. The present work is
focused on the interaction of the various portions of APP with the three domains
of Netrin-1, the so-called LamNT, EGF-like and NTR domains respectively. It
reveals in detail which portions of APP and Netrin-1 are specifically involved in
these interactions, using ELISA technique in combination with protein-protein
binding simulations. So far unsuspected interaction sites located in Netrin-1 EGF
like and NTR domains open possibilities for new therapeutic approaches in which
these sites will be specifically targeted.
PMID- 28501619
TI - A label-free immunoassay for Flavivirus detection by the Reflective Phantom
Interface technology.
AB - Flaviviruses are widespread and cause clinically relevant arboviral diseases that
impact locally and as imported travel-related infections. Direct detection of
viraemia is limited, being typically undetectable at onset of symptoms.
Therefore, diagnosis is primarily based on serology, which is complicated by high
cross-reactivity across different species. The overlapping geographical
distribution of the vectors in areas with a weak healthcare system, the increase
of international travel and the similarity of symptoms highlight the need for
rapid and reliable multi-parametric diagnostic tests in point-of-care formats. To
this end we developed a bi-parametric serological microarray using recombinant
NS1 proteins from Tick-borne encephalitis virus and West Nile virus coupled to a
low-cost, label-free detection device based on the Reflective Phantom Interface
(RPI) principle. Specific sequential detection of antibodies in solution
demonstrates the feasibility of the approach for the surveillance and diagnosis
of Flaviviruses.
PMID- 28501621
TI - Discovery of a novel prolyl-tRNA synthetase inhibitor and elucidation of its
binding mode to the ATP site in complex with l-proline.
AB - Prolyl-tRNA synthetase (PRS) is a member of the aminoacyl-tRNA synthetase family
of enzymes and catalyzes the synthesis of prolyl-tRNAPro using ATP, l-proline,
and tRNAPro as substrates. An ATP-dependent PRS inhibitor, halofuginone, was
shown to suppress autoimmune responses, suggesting that the inhibition of PRS is
a potential therapeutic approach for inflammatory diseases. Although a few PRS
inhibitors have been derivatized from natural sources or substrate mimetics,
small-molecule human PRS inhibitors have not been reported. In this study, we
discovered a novel series of pyrazinamide PRS inhibitors from a compound library
using pre-transfer editing activity of human PRS enzyme. Steady-state biochemical
analysis on the inhibitory mode revealed its distinctive characteristics of
inhibition with proline uncompetition and ATP competition. The binding activity
of a representative compound was time-dependently potentiated by the presence of
l-proline with Kd of 0.76 nM. Thermal shift assays demonstrated the stabilization
of PRS in complex with l-proline and pyrazinamide PRS inhibitors. The binding
mode of the PRS inhibitor to the ATP site of PRS enzyme was elucidated using the
ternary complex crystal structure with l-proline. The results demonstrated the
different inhibitory and binding mode of pyrazinamide PRS inhibitors from
preceding halofuginone. Furthermore, the PRS inhibitor inhibited intracellular
protein synthesis via a different mode than halofuginone. In conclusion, we have
identified a novel drug-like PRS inhibitor with a distinctive binding mode. This
inhibitor was effective in a cellular context. Thus, the series of PRS inhibitors
are considered to be applicable to further development with differentiation from
preceding halofuginone.
PMID- 28501622
TI - The role of plasmin in the pathogenesis of murine multiple myeloma.
AB - Aside from a role in clot dissolution, the fibrinolytic factor, plasmin is
implicated in tumorigenesis. Although abnormalities of coagulation and
fibrinolysis have been reported in multiple myeloma patients, the biological
roles of fibrinolytic factors in multiple myeloma (MM) using in vivo models have
not been elucidated. In this study, we established a murine model of fulminant MM
with bone marrow and extramedullar engraftment after intravenous injection of B53
cells. We found that the fibrinolytic factor expression pattern in murine B53 MM
cells is similar to the expression pattern reported in primary human MM cells.
Pharmacological targeting of plasmin using the plasmin inhibitors YO-2 did not
change disease progression in MM cell bearing mice although systemic plasmin
levels was suppressed. Our findings suggest that although plasmin has been
suggested to be a driver for disease progression using clinical patient samples
in MM using mostly in vitro studies, here we demonstrate that suppression of
plasmin generation or inhibition of plasmin cannot alter MM progression in vivo.
PMID- 28501623
TI - Efficient direct conversion of human fibroblasts into myogenic lineage induced by
co-transduction with MYCL and MYOD1.
AB - The skeletal muscle consists of contractile myofibers and plays essential roles
for maintenance of body posture, movement, and metabolic regulation. During the
development and regeneration of the skeletal muscle tissue, the myoblasts fuse
into multinucleated myotubes that subsequently form myofibers. Transplantation of
myoblasts may make possible a novel regenerative therapy against defects or
dysfunction of the skeletal muscle. It is reported that rodent fibroblasts are
converted into myoblast-like cells and fuse to form syncytium after forced
expression of exogenous myogenic differentiation 1 (MYOD1) that is a key
transcription factor for myoblast differentiation. But human fibroblasts are less
efficiently converted into myoblasts and rarely fused by MYOD1 alone. Here we
found that transduction of v-myc avian myelocytomatosis viral oncogene lung
carcinoma derived homolog (MYCL) gene in combination with MYOD1 gene induced
myoblast-like phenotypes in human fibroblasts more strongly than MYOD1 gene
alone. The rate of conversion was approximately 90%. The directly converted
myoblasts (dMBs) underwent fusion in an ERK5 pathway-dependent manner. The dMBs
also formed myofiber-like structure in vivo after an inoculation into mice at the
subcutaneous tissue. The present results strongly suggest that the combination of
MYCL plus MYOD1 may promote direct conversion of human fibroblasts into
functional myoblasts that could potentially be used for regenerative therapy for
muscle diseases and congenital muscle defects.
PMID- 28501624
TI - Autophagy is essential for the differentiation of porcine PSCs into insulin
producing cells.
AB - Porcine pancreatic stem cells (PSCs) are seed cells with potential use for
diabetes treatment. Stem cell differentiation requires strict control of protein
turnover and lysosomal digestion of organelles. Autophagy is a highly conserved
process that controls the turnover of organelles and proteins within cells and
contributes to the balance of cellular components. However, whether autophagy
plays roles in PSC differentiation remains unknown. In this study, we
successfully induced porcine PSCs into insulin-producing cells and found that
autophagy was activated during the second induction stage. Inhibition of
autophagy in the second stage resulted in reduced differentiational efficiency
and impaired glucose-stimulated insulin secretion. Moreover, the expression of
active beta-catenin increased while autophagy was activated but was suppressed
when autophagy was inhibited. Therefore, autophagy is essential to the formation
of insulin-producing cells, and the effects of autophagy on differentiation may
be regulated by canonical Wnt signalling pathway.
PMID- 28501625
TI - Circular RNAs roll into the regulatory network of plants.
AB - As a novel class of endogenous non-coding RNAs, circular RNAs (circRNAs) have
become a new research hotspot in recent years. The wide distribution of circRNAs
in different plant species has been proven. Furthermore, circRNAs show
significant tissue-specific expression patterns in plant development and are
responsive to a variety of biotic and abiotic stresses, indicating that circRNAs
might have important biological functions in plant development. Here, we
summarize the current knowledge of plant circRNAs in recent years and discuss
views and perspectives on the possible regulatory roles of plant circRNAs,
including the function of miRNA sponges, regulating the expression of their
parental genes or linear mRNAs, translating into peptides or proteins and
responses to different stresses. These advances have sculpted a framework of
plant circRNAs and provide new insights for functional RNA regulation research in
the future.
PMID- 28501626
TI - A method for the detection of virus infectivity in single cells and real time:
Towards an automated fluorescence neutralization test.
AB - Virus neutralizing antibodies are critical correlates of protection in vaccine
development and are discriminatory in the plaque reduction neutralization test
when used for the diagnosis of viral infections. However, neutralization assays
are time consuming, labor intensive and highly variable, thus limiting their use.
Advances in automated live imaging of cells opened new possibilities for standard
virus diagnostic techniques such as neutralization assays. To this end, a
reporter cell line based on the translocation of the transcription factor IRF3 in
response to infection is proposed. Image acquisition of signal in a microplate
format allowed the setup of a rapid, semi-automated and high-throughput
fluorescent neutralization test. The study is extended to the live imaging of
IRF3 translocations that could potentially cut the time of analysis to few hours.
The fluorescent neutralization test is suitable for high-throughput assays and
expandable to other viruses of global importance such as Zika virus.
PMID- 28501627
TI - Detection of viromes of RNA viruses using the next generation sequencing
libraries prepared by three methods.
AB - Virome (viral megagenomics) detection using next generation sequencing has been
widely applied in virology, but its methods remain complicated and need
optimization. In this study, we detected the viromes of RNA viruses of one mock
sample, one pooled duck feces sample and one pooled mink feces sample on the
Personal Genome Machine platform using the sequencing libraries prepared by three
methods. The sequencing primers were added through random hybridization and
ligation to fragmented viral RNA using a RNA-Seq kit in method 1, through random
reverse transcription (RT) and polymerase chain reaction (PCR) in method 2 which
was developed in our laboratory, and through hybridization and ligation to
fragmented amplicons of random RT-PCR using a single primer in method 3. Although
the results of these three samples (nine libraries) all showed that more
classified viral families and genera were identified using methods 2 and 3 than
using method 1, and more classified viral families and genera were identified
using method 2 than using method 3, most of the differences were of no
statistical significance. Moreover, 11 mammalian viral genera in minks were
possibly identified for the first time through this study.
PMID- 28501628
TI - Evolutionary expansion and structural functionalism of the ancient family of
profilin proteins.
AB - Structure and functional similarities of a recent protein's orthologs with its
ancient counterpart are largely determined by the configuration of evolutionary
preservation of amino acids. The emergence of genome sequencing databases allowed
dissecting the evolutionarily important gene families at a comprehensive and
genome-wide scale. The profilin multi-gene family is an ancient, universal, and
functionally diverged across kingdoms, which regulates various aspects of
cellular development in both prokarya and eukarya, especially cell-wall
maintenance through actin sequestering, nucleation and cytokinesis. We performed
a meta-analysis of the evolutionary expansion, structural conservation, evolution
of function motifs, and transcriptional biases of profilin proteins across
kingdoms. An exhaustive search of various genome databases of cyanobacteria,
fungi, animalia and plantae kingdoms revealed 172 paralogous/orthologous
profilins those were phylogenetically clustered in various groups. Orthologous
gene comparisons indicated that segmental and tandem duplication events under
strong purifying selection are predominantly responsible for their convoluted
structural divergences. Evidently, structural divergences were more prevalent in
the paralogs than orthologs, and evolutionary variations in the exon/intron
architecture were accomplished by 'exon/intron-gain' and insertion/deletion
during sequence-exonization. Remarkably, temporal expression evolution of
profilin paralogs/homeologs during cotton fiber domestication provides
evolutionary impressions of the selection of highly diverged transcript abundance
notably in the fiber morpho-evolution. These results provide global insights into
the profilin evolution, their structural design across taxa; and their future
utilization in translational research.
PMID- 28501629
TI - Statistical support for Sema3A and multiple sclerosis.
PMID- 28501630
TI - Identification of potential crucial genes associated with steroid-induced
necrosis of femoral head based on gene expression profile.
AB - The aim of this study was to explore potential crucial genes associated with the
steroid-induced necrosis of femoral head (SINFH) and to provide valid biological
information for further investigation of SINFH. Gene expression profile of
GSE26316, generated from 3 SINFH rat samples and 3 normal rat samples were
downloaded from Gene Expression Omnibus (GEO) database. The differentially
expressed genes (DEGs) were identified using LIMMA package. After functional
enrichment analyses of DEGs, protein-protein interaction (PPI) network and sub
PPI network analyses were conducted based on the STRING database and cytoscape.
In total, 59 up-regulated DEGs and 156 downregulated DEGs were identified. The up
regulated DEGs were mainly involved in functions about immunity (e.g. Fcer1A and
Il7R), and the downregulated DEGs were mainly enriched in muscle system process
(e.g. Tnni2, Mylpf and Myl1). The PPI network of DEGs consisted of 123 nodes and
300 interactions. Tnni2, Mylpf, and Myl1 were the top 3 outstanding genes based
on both subgraph centrality and degree centrality evaluation. These three genes
interacted with each other in the network. Furthermore, the significant network
module was composed of 22 downregulated genes (e.g. Tnni2, Mylpf and Myl1). These
genes were mainly enriched in functions like muscle system process. The DEGs
related to the regulation of immune system process (e.g. Fcer1A and Il7R), and
DEGs correlated with muscle system process (e.g. Tnni2, Mylpf and Myl1) may be
closely associated with the progress of SINFH, which is still needed to be
confirmed by experiments.
PMID- 28501631
TI - Plasmid transfection in bovine cells: Optimization using a realtime monitoring of
green fluorescent protein and effect on gene reporter assay.
AB - Gene reporter technology (GRT) has opened several new avenues for monitoring
biological events including the activation of transcription factors, which are
central to the study of nutrigenomics. However, this technology relies heavily on
the insertion of foreign plasmid DNA into the nuclei of cells (i.e.,
transfection), which can be very challenging and highly variable among cell
types. The objective of this study was to investigate the optimal conditions to
generate reliable GRT assay data on bovine immortalized cell lines, Madin Darby
Bovine Kidney (MDBK) and bovine mammary epithelial alveolar (MACT) cells. Results
are reported for two experiments. In Experiment 1, using 96 well-plate and a
robotic inverted fluorescent microscope, we compared transfection efficiency
among commercially available transfection reagents (TR) Lipofectamine(r) 3000
(Lipo3), Lipofectamine(r) LTX (LipoLTX), and TransIT-X2(r) (TransX2), three doses
of TR (i.e., 0.15, 0.3, and 0.4MUL/well), and three doses of Green Fluorescent
Protein plasmid DNA (i.e., 10, 25, and 50ng/well). Transfection efficiency and
mortality rate were analyzed using CellProfiler software. Transfection efficiency
increased until the end of the experiment (20h post-transfection) at which point
MACT had greater transfection than MDBK cells (16.3% vs. 2.2%). It is unclear the
reason for the low transfection in MDBK cells. Maximal transfection efficiency
was obtained with 0.3MUL/well of LipoLTX plus 25ng/well of plasmid DNA (ca.
29.5+/-1.9%) and 0.15MUL/well of LipoLTX plus 25ng/well of plasmid DNA (ca. 4.0+/
0.4%) for MACT and MDBK cells, respectively. The higher amount of TR and DNA was
generally associated with higher cell mortality. Using high, medium, and low
transfection efficiency conditions determined in Experiment 1, we performed a GRT
assay for peroxisome proliferator-activated response element (PPRE) luciferase in
MACT and MDBK cells treated with 10nM or 100nM of synthetic Peroxisome
Proliferator-activated Receptor beta/sigma (PPARbeta/sigma) agonist. The GRT
assay was unaffected by poor transfection in MACT cells although the high
transfection hampered the possibility of detecting differences between 10 and
100nM of the PPARbeta/delta agonist. In MDBK cells, low transfection efficiency
(<2.0%) failed to detect any differences with GRT assay. The level of
transfection was positively associated with a lower coefficient of variation of
GRT data. Overall, our data indicates that results of GRT assays are affected by
transfection efficiency and a minimum transfection of 2% is required. Thus,
factors such as TR type, TR amount, and DNA plasmid amount need to be optimized
for a specific cell type before performing GRT assays.
PMID- 28501632
TI - High levels of maternally transferred mercury disrupt magnetic responses of
snapping turtle hatchlings (Chelydra serpentina).
AB - The Earth's magnetic field is involved in spatial behaviours ranging from long
distance migration to non-goal directed behaviours, such as spontaneous magnetic
alignment (SMA). Mercury is a harmful pollutant most often generated from
anthropogenic sources that can bio-accumulate in animal tissue over a lifetime.
We compared SMA of hatchling snapping turtles from mothers captured at reference
(i.e., low mercury) and mercury contaminated sites. Reference turtles showed
radio frequency-dependent SMA along the north-south axis, consistent with
previous studies of SMA, while turtles with high levels of maternally inherited
mercury failed to show consistent magnetic alignment. In contrast, there was no
difference between reference and mercury exposed turtles on standard performance
measures. The magnetic field plays an important role in animal orientation
behaviour and may also help to integrate spatial information from a variety of
sensory modalities. As a consequence, mercury may compromise the performance of
turtles in a wide variety of spatial tasks. Future research is needed to
determine the threshold for mercury effects on snapping turtles, whether mercury
exposure compromises spatial behaviour of adult turtles, and whether mercury has
a direct effect on the magnetoreception mechanism(s) that mediate SMA or a more
general effect on the nervous system.
PMID- 28501633
TI - Atmospheric mercury deposition to forests in the eastern USA.
AB - Atmospheric mercury (Hg) deposition to forests is important because half of the
land cover in the eastern USA is forest. Mercury was measured in autumn
litterfall and weekly precipitation samples at a total of 27 National Atmospheric
Deposition Program (NADP) monitoring sites in deciduous and mixed deciduous
coniferous forests in 16 states in the eastern USA during 2007-2014. These
simultaneous, uniform, repeated, annual measurements of forest Hg include the
broadest area and longest time frame to date. The autumn litterfall-Hg
concentrations and litterfall mass at the study sites each year were combined
with annual precipitation-Hg data. Rates of litterfall-Hg deposition were higher
than or equal to precipitation-Hg deposition rates in 70% of the annual data,
which indicates a substantial contribution from litterfall to total atmospheric
Hg deposition. Annual litterfall-Hg deposition in this study had a median of 11.7
MUg per square meter per year (MUg/m2/yr) and ranged from 2.2 to 23.4 MUg/m2/yr.
It closely matched modeled dry-Hg deposition, based on land cover at selected
NADP Hg-monitoring sites. Mean annual atmospheric-Hg deposition at forest study
sites exhibited a spatial pattern partly explained by statistical differences
among five forest-cover types and related to the mapped density of Hg emissions.
Forest canopies apparently recorded changes in atmospheric-Hg concentrations over
time because litterfall-Hg concentrations decreased year to year and litterfall
Hg concentrations were significantly higher in 2007-2009 than in 2012-2014. These
findings reinforce reported decreases in Hg emissions and atmospheric elemental
Hg concentrations during this same time period. Methylmercury (MeHg) was detected
in all litterfall samples at all sites, compared with MeHg detections in less
than half the precipitation samples at selected sites during the study. These
results indicate MeHg in litterfall is a pathway into the terrestrial food web
where it can accumulate in the prey of songbirds, bats, and raptors.
PMID- 28501634
TI - Helminth infracommunity of the cane toad Rhinella marina (Anura: Bufonidae)
within its native distribution range.
AB - During August 2010, a total of 66 cane toad Rhinella marina were collected in
Laguna de Coyuca, Guerrero, Mexico and examined for the presence of helminths.
Ninety-two percent were parasitized by 1 or more parasite species. A total of
4624 individuals were found, belonging to 8 helminth taxa (1 digenean, 1 cestode
and 6 nematodes). Infracommunities harbored by this host species are highly
variable (mean Jaccard similarity index 0.31+/-0.27); mean percent similarity
index 0.26+/-0.32) and depauperate (mean richness 1.91+/-0.92; mean abundance
64.4+/-100.34); almost 50% of them were dominated by Rhabdias fuelleborni, a skin
penetrating nematode. Differences related to host gender and size were found,
since males registered infracommunities with lower species richness and diversity
than females. The reproductive condition of females (collected during the
breeding season) might explain the results obtained; during this season, females
invest less in resistance to infection in favor of investing resources in
reproduction. However, confirmation of this statement can only be made by
sampling in the dry season, when the toads do not reach their reproductive peak.
PMID- 28501635
TI - Determining the role of inflammation in the selection of JAK2 mutant cells in
myeloproliferative neoplasms.
AB - Myeloproliferative neoplasm (MPN) is a hematologic malignancy characterized by
the clonal outgrowth of hematopoietic cells with a somatically acquired mutation
most commonly in JAK2 (JAK2V617F). This mutation endows upon myeloid progenitors
cytokine independent growth and consequently leads to excessive production of
myeloid lineage cells. It has been previously suggested that inflammation may
play a role in the clonal evolution of JAK2V617F mutants. In particular, it is
possible that one or more cellular kinetic parameters of hematopoietic stem cells
(HSCs) are affected by inflammation, such as division or death rates of cells,
and the probability of HSC differentiation. This suggests a mechanism that can
steer the outcome of the cellular competition in favor of the mutants, initiating
the disease. In this paper we create a number of mathematical evolutionary
models, from very abstract to more concrete, that describe cellular competition
in the context of inflammation. It is possible to build a model axiomatically,
where only very general assumptions are imposed on the modeling components and no
arbitrary (and generally unknown) functional forms are used, and still generate a
set of testable predictions. In particular, we show that, if HSC death is
negligible, the evolutionary advantage of mutant cells can only be conferred by
an increase in differentiation probability of HSCs in the presence of
inflammation, and if death plays a significant role in the dynamics, an
additional mechanism may be an increase of HSC's division-to-death ratio in the
presence of inflammation. Further, we show that in the presence of inflammation,
the wild type cell population is predicted to shrink under inflammation (even in
the absence of mutants). Finally, it turns out that if only the differentiation
probability is affected by the inflammation, then the resulting steady state
population of wild type cells will contain a relatively smaller percentage of
HSCs under inflammation. If the division-to-death rate is also affected, then the
percentage of HSCs under inflammation can either decrease or increase, depending
on other parameters.
PMID- 28501638
TI - Nitrogen rich core-shell magnetic mesoporous silica as an effective adsorbent for
removal of silver nanoparticles from water.
AB - The production and increasing use of silver nanoparticles (AgNPs) obviously
results in their release into the environment, leading to a risk to the
environment due to their toxic effects. Thus, the removal of AgNPs from water is
highly needed. Here, we demonstrate that nitrogen rich (~10% nitrogen content)
core-shell magnetic mesoporous silica is a promising adsorbent for the removal of
AgNPs. For this, the poly(ethylenimine) functionalized core-shell magnetic
mesoporous silica composites (Fe3O4@SiO2-PEI) were prepared, and characterized by
TEM, FT-IR, XRD, TG and N2 adsorption-desorption. The removal of AgNPs by
Fe3O4@SiO2-PEI as a function of contact time, concentration of AgNPs, solution pH
and ionic strength were studied. The adsorption kinetic data could be described
by the pseudo-second-order rate model. Both Langmuir and Freundlich models fitted
the adsorption data well. The adsorption capacity for AgNPs is 909.1mg/g, which
is 5-181 times higher than that of the previously reported adsorbents for AgNPs.
Interestingly, the silver adsorbed onto Fe3O4@SiO2-PEI exhibits highly catalytic
activity for 4-nitropheol (4-NP) reduction with a rate constant of 0.072min-1,
which is much higher than those by other AgNPs reported before. The silver-loaded
Fe3O4@SiO2-PEI promises good recyclability for at least five cycles, showing
great potential in practical applications.
PMID- 28501637
TI - Serial endosymbiosis or singular event at the origin of eukaryotes?
AB - 'On the Origin of Mitosing Cells' heralded a new way of seeing cellular
evolution, with symbiosis at its heart. Lynn Margulis (then Sagan) marshalled an
impressive array of evidence for endosymbiosis, from cell biology to atmospheric
chemistry and Earth history. Despite her emphasis on symbiosis, she saw plenty of
evidence for gradualism in eukaryotic evolution, with multiple origins of mitosis
and sex, repeated acquisitions of plastids, and putative evolutionary
intermediates throughout the microbial world. Later on, Margulis maintained her
view of multiple endosymbioses giving rise to other organelles such as
hydrogenosomes, in keeping with the polyphyletic assumptions of the serial
endosymbiosis theory. She stood at the threshold of the phylogenetic era, and
anticipated its potential. Yet while predicting that the nucleotide sequences of
genes would enable a detailed reconstruction of eukaryotic evolution, Margulis
did not, and could not, imagine the radically different story that would
eventually emerge from comparative genomics. The last eukaryotic common ancestor
now seems to have been essentially a modern eukaryotic cell that had already
evolved mitosis, meiotic sex, organelles and endomembrane systems. The long
search for missing evolutionary intermediates has failed to turn up a single
example, and those discussed by Margulis turn out to have evolved reductively
from more complex ancestors. Strikingly, Margulis argued that all eukaryotes had
mitochondria in her 1967 paper (a conclusion that she later disavowed). But she
developed her ideas in the context of atmospheric oxygen and aerobic respiration,
neither of which is consistent with more recent geological and phylogenetic
findings. Instead, a modern synthesis of genomics and bioenergetics points to the
endosymbiotic restructuring of eukaryotic genomes in relation to bioenergetic
membranes as the singular event that permitted the evolution of morphological
complexity.
PMID- 28501636
TI - Determining whether observed eukaryotic cell migration indicates chemotactic
responsiveness or random chemokinetic motion.
AB - Chemotaxis, the motion of cells directed by a gradient of chemoattractant
molecules, guides cells in immune response, development, wound healing, and
cancer. Unfortunately, this process is difficult to distinguish from
chemokinesis, i.e., stimulated random cell motion. Chemotaxis is frequently
inferred by determining how many cells cross a boundary in a chemotaxis assay,
for example how many cells crawl into a chemoattractant-infused filter, or how
many cells enter a defined region in an under-agarose assay or agarose spot
assay. To mitigate possible ambiguity in whether motion observed in these assays
is directed by the chemoattractant gradient or by chemokinesis, we developed a
mathematical model to determine when such methods indeed indicate directed motion
of cells. In contrast to previous analyses of chemotaxis assays, we report not
just the gradients that arise in the assays but also resulting cell motion. We
applied the model to data obtained from rigorous measurements and show, as
examples, that MDA-MB-231 breast-cancer cells are at least 20 times less
sensitive to gradients of EGF or CXCL12 than neutrophils are to formyl peptides;
we then used this information to determine the extent to which gradient sensing
increases the rate of boundary crossing relative to a random-motility control.
Results show, for example, that in the filter assay, 2-4 times as many
neutrophils pass through the filter when exposed to a gradient as when the
gradient is absent. However, in the other combinations of cells and assays we
considered, only 10-20% more cells are counted as having migrated in a directed,
rather than random, motility condition. We also discuss the design of appropriate
controls for these assays, which is difficult for the under-agarose and agarose
spot assays. Moreover, although straightforward to perform with the filter assay,
reliable controls are often not done. Consequently, we infer that chemotaxis is
frequently over-reported, especially for cells like MDA-MB-231 cells, which move
slowly and are relatively insensitive to gradients. Such results provide insights
into the use of chemotaxis assays, particularly if one wants to acquire and
analyze quantitative data.
PMID- 28501639
TI - Comparative evaluation of thermal decomposition behavior and thermal stability of
powdered ammonium nitrate under different atmosphere conditions.
AB - In order to analyze the thermal decomposition characteristics of ammonium nitrate
(AN), its thermal behavior and stability under different conditions are studied,
including different atmospheres, heating rates and gas flow rates. The evolved
decomposition gases of AN in air and nitrogen are analyzed with a quadrupole mass
spectrometer. Thermal stability of AN at different heating rates and gas flow
rates are studied by differential scanning calorimetry, thermogravimetric
analysis, paired comparison method and safety parameter evaluation. Experimental
results show that the major evolved decomposition gases in air are H2O, NH3, N2O,
NO, NO2 and HNO3, while in nitrogen, H2O, NH3, NO and HNO3 are major components.
Compared with nitrogen atmosphere, lower initial and end temperatures, higher
heat flux and broader reaction temperature range are obtained in air. Meanwhile,
higher air gas flow rate tends to achieve lower reaction temperature and to
reduce thermal stability of AN. Self-accelerating decomposition temperature of AN
in air is much lower than that in nitrogen. It is considered that thermostability
of AN is influenced by atmosphere, heating rate and gas flow rate, thus changes
of boundary conditions will influence its thermostability, which is helpful to
its safe production, storage, transportation and utilization.
PMID- 28501640
TI - Rapid immobilization of simulated radioactive soil waste by microwave sintering.
AB - A rapid and efficient method is particularly necessary in the timely disposal of
seriously radioactive contaminated soil. In this paper, a series of simulated
radioactive soil waste containing different contents of neodymium oxide (3
25wt.%) has been successfully vitrified by microwave sintering at 1300 degrees C
for 30min. The microstructures, morphology, element distribution, density and
chemical durability of as obtained vitrified forms have been analyzed. The
results show that the amorphous structure, homogeneous element distribution, and
regular density improvement are well kept, except slight cracks emerge on the
magnified surface for the 25wt.% Nd2O3-containing sample. Moreover, all the
vitrified forms exhibit excellent chemical durability, and the leaching rates of
Nd are kept as ~10-4-10-6g/(m2day) within 42days. This demonstrates a potential
application of microwave sintering in radioactive contaminated soil disposal.
PMID- 28501641
TI - Facile preparation of 3D GO/CNCs composite with adsorption performance towards
[BMIM][Cl] from aqueous solution.
AB - A novel three-dimensional crumpled graphene oxide/cellulose nanocrystals
(GO/CNCs) composite was successfully synthesized and firstly used as adsorbent
for the removal of ionic liquid [BMIM][Cl] from aqueous solution. The 3D crumpled
structure and abundant oxygen of the functional groups on GO/CNCs composite can
provide more chance for the sorption of [BMIM][Cl] compared with CNCs and GO,
respectively. Therefore, a series of batch experiments were carried out to
evaluate the adsorptive property of 3D GO/CNCs composite towards [BMIM][Cl], such
as the GO mass content, the pH value and contact time. The results showed that
pseudo-second-order kinetic model and Eovlich model were well fitted with the
sorption kinetic. The isotherm adsorption data indicated that it was better
described by Langmuir model, with the maximum sorption capacity of 0.455mmol/g.
This work provides a facile method for the preparation of 3D structure adsorbent
from graphene oxide and cellulose nanocrystals which has high adsorption capacity
of [BMIM][Cl] in aqueous solution.
PMID- 28501643
TI - Efficient wastewater treatment and simultaneously electricity production using a
photocatalytic fuel cell based on the radical chain reactions initiated by dual
photoelectrodes.
AB - Efficient conversion of wastewater into clean energy was achieved by applying a
radical chain reaction strategy in a solar responsive photocatalytic fuel cell
(PFC) system. The system was constructed with two photoelectrodes where ferrous
ions were added to enhance the radical reactions for organic pollutants
degradation from the surface of electrodes to the whole solution system via
coming into a continuous radical chain reaction. The results indicated that the
short-circuit current (Jsc) and the power density (JVmax) obtained in the PFC
system is up to 1.41-1.60 and 1.52-2.02 times larger than those of the PFC
without ferrous ions. Meanwhile, the degradation rate of refractory organics
(methyl orange, methylene blue, congo red and tetracycline) increased to 91.98%,
98.57%, 92.36% and 68.09% from 53.61%, 45.38%, 51.09% and 30.65% respectively
after 90min operation. The proposed PFC with a radical chain reaction strategy
provides a more economical and efficient way for energy recovery and wastewater
treatment and implies a possibility of developing much higher efficient PFC
system when applying the other electrodes.
PMID- 28501642
TI - A novel method for photo-oxidative degradation of diatrizoate in water via
electromagnetic induction electrodeless lamp.
AB - In this study, an electromagnetic induction electrodeless lamp (EIEL) was first
introduced into UV advanced oxidation processes (AOPs) for photodegradation of
Diatrizoate (DTZ), which was the most persistent iodinated X-ray contrast medium
(ICM), and traditional Hg lamps were taken as references. Direct photolysis rate
of DTZ under EIEL irradiation was 1.34 times as that under Hg irradiation, but
the electric energy consumption was 0.87 times. In this sense, the combination of
EIEL and oxidants (O2, H2O2 and S2O82-(PS)) was further investigated. The
remarkably increased photodegradation rates were observed in UV/PS system due to
primary contribution rate of SO4- (62.5%) based on the results of radical
concentrations and second-order rate constants of DTZ with SO4- and OH. Inorganic
ions influencing the photodegradation process were investigated. The effect of
natural organic materials (NOMs) in UV/PS system was studied based on
contribution ratios of light screening effect and quenching. Transformation
mechanisms of DTZ in UV/PS system included deiodination, intramolecular
cyclization, decarboxylation, deacetylation and deamination, which were further
confirmed by frontier electron density calculations. The study indicated that
UV/PS with EIEL irradiation has the potential to remove pharmaceuticals in
contaminated aquatic environments.
PMID- 28501644
TI - Mechanistic and computational studies of PCB 151 dechlorination by zero valent
magnesium for field remediation optimization.
AB - Polychlorinated biphenyls (PCBs) are banned in the U.S. but are persistent in the
environment; current regulations provide an urgent need to remediate PCBs in a
cost-effective way. In prior work, a novel method of degradation of PCBs via
hydrodehalogenation with ball milled zero-valent magnesium and activated carbon
showed promising results even with water present in the system. In this research,
a detailed study of the byproducts formed in the dechlorination process for PCB
151 (used as an example of hexa-chlorinated PCB) and a study of the mechanism
involved in this reaction via density functional theory (DFT) computations are
presented. It was demonstrated that these reactions are exothermic and involved
two transition states, the formation of the ionic transition state being the rate
limiting step of the reaction. The torsion angle of the PCB congeners was also
shown to be an extremely important factor to be able to use activated carbon as
part of the remediation process.
PMID- 28501645
TI - Targeted sequencing identifies novel variants involved in autosomal recessive
hereditary hearing loss in Qatari families.
AB - Hereditary hearing loss is characterized by a very high genetic heterogeneity. In
the Qatari population the role of GJB2, the worldwide HHL major player, seems to
be quite limited compared to Caucasian populations. In this study we analysed 18
Qatari families affected by non-syndromic hearing loss using a targeted
sequencing approach that allowed us to analyse 81 genes simultaneously. Thanks to
this approach, 50% of these families (9 out of 18) resulted positive for the
presence of likely causative alleles in 6 different genes: CDH23, MYO6, GJB6,
OTOF, TMC1 and OTOA. In particular, 4 novel alleles were detected while the
remaining ones were already described to be associated to HHL in other ethnic
groups. Molecular modelling has been used to further investigate the role of
novel alleles identified in CDH23 and TMC1 genes demonstrating their crucial role
in Ca2+ binding and therefore possible functional role in proteins. Present study
showed that an accurate molecular diagnosis based on next generation sequencing
technologies might largely improve molecular diagnostics outcome leading to
benefits for both genetic counseling and definition of recurrence risk.
PMID- 28501647
TI - Application of optical action potentials in human induced pluripotent stem cells
derived cardiomyocytes to predict drug-induced cardiac arrhythmias.
AB - INTRODUCTION: Human induced pluripotent stem cell-derived cardiomyocytes (hiPS
CMs) are emerging as new and human-relevant source in vitro model for cardiac
safety assessment that allow us to investigate a set of 20 reference drugs for
predicting cardiac arrhythmogenic liability using optical action potential (oAP)
assay. METHODS: Here, we describe our examination of the oAP measurement using a
voltage sensitive dye (Di-4-ANEPPS) to predict adverse compound effects using
hiPS-CMs and 20 cardioactive reference compounds. Fluorescence signals were
digitized at 10kHz and the records subsequently analyzed off-line. Cells were
exposed to 30min incubation to vehicle or compound (n=5/dose, 4 doses/compound)
that were blinded to the investigating laboratory. Action potential parameters
were measured, including rise time (Trise) of the optical action potential
duration (oAPD). RESULTS: Significant effects on oAPD were sensitively detected
with 11 QT-prolonging drugs, while oAPD shortening was observed with ICa
antagonists, IKr-activator or ATP-sensitive K+ channel (KATP)-opener.
Additionally, the assay detected varied effects induced by 6 different sodium
channel blockers. The detection threshold for these drug effects was at or below
the published values of free effective therapeutic plasma levels or effective
concentrations by other studies. DISCUSSION: The results of this blinded study
indicate that OAP is a sensitive method to accurately detect drug-induced effects
(i.e., duration/QT-prolongation, shortening, beat rate, and incidence of early
after depolarizations) in hiPS-CMs; therefore, this technique will potentially be
useful in predicting drug-induced arrhythmogenic liabilities in early de-risking
within the drug discovery phase.
PMID- 28501646
TI - Developing a framework for digital objects in the Big Data to Knowledge (BD2K)
commons: Report from the Commons Framework Pilots workshop.
AB - The volume and diversity of data in biomedical research have been rapidly
increasing in recent years. While such data hold significant promise for
accelerating discovery, their use entails many challenges including: the need for
adequate computational infrastructure, secure processes for data sharing and
access, tools that allow researchers to find and integrate diverse datasets, and
standardized methods of analysis. These are just some elements of a complex
ecosystem that needs to be built to support the rapid accumulation of these data.
The NIH Big Data to Knowledge (BD2K) initiative aims to facilitate digitally
enabled biomedical research. Within the BD2K framework, the Commons initiative is
intended to establish a virtual environment that will facilitate the use,
interoperability, and discoverability of shared digital objects used for
research. The BD2K Commons Framework Pilots Working Group (CFPWG) was established
to clarify goals and work on pilot projects that address existing gaps toward
realizing the vision of the BD2K Commons. This report reviews highlights from a
two-day meeting involving the BD2K CFPWG to provide insights on trends and
considerations in advancing Big Data science for biomedical research in the
United States.
PMID- 28501648
TI - Tetrahydroacridine derivatives with fluorobenzoic acid moiety as multifunctional
agents for Alzheimer's disease treatment.
AB - A novel series of 9-amino-1,2,3,4-tetrahydroacridine derivatives with 2
fluorobenzoic acid or 3-fluorobenzoic acid moiety were designed, synthesized and
evaluated as inhibitors of cholinesterases and aggregation of beta-amyloid. In
the study target compounds were very potent inhibitors of AChE and BChE. The most
promising agents had higher inhibitory potency than the reference drugs which was
tacrine. Ultimately, the kinetic assay shows the most active target compound 3c
against AChE. Almost all of them were more potent against BChE than AChE.
Compound 3c in various concentrations was tested by aggregation experiment.
Inhibition of beta-amyloid aggregation was 77.32% and 80.43% at 50uM and 100uM,
respectively. Therefore, compound 3c is a promising agent for the treatment of
AD.
PMID- 28501649
TI - Different activation of monocyte-derived macrophages by antimicrobial peptides at
a titanium tibial implantation in rabbits.
AB - The aim of our study was to assess the functional and morphological features of
monocyte derived Mfs from rabbits with titanium (Ti) tibial implants, their
ability to polarize towards M1 or M2 and their reactivity after stimulation with
neutrophil antimicrobial peptides extract (AMP). The study was conducted on six
White New Zealand rabbits with tibial implants of pure titanium Grade 2. Blood
was taken before implantation and 14days after biomaterial implantation. Then,
blood-derived Mfs were cultured and their function was assessed on the basis of
morphological changes, generation of nitric oxide (NO), superoxide, and proteases
release after treatment with LPS or dexamethasone (Dex). As a result of
polarization we specified two subpopulations of Mfs with features characteristic
of each subtype. M1 stimulated with LPS exhibited an increased NO and superoxide
level, and M2 stimulated with Dex which showed higher arginase and lower free
radical generation. Addition of AMP evoked further changes in Mfs morphology and
function. After 24h stimulation with AMP an increase of NO was observed in all
cultures, whereas after 48h it decreased. Production of superoxide lowered,
especially after 48h, when M1 generated 6.00+/-0.2nM and M1/AMP culture generated
5.2+/-0.1nM of superoxide. Our study revealed that activated Mfs stimulated with
AMP demonstrated both pro- and anti-inflammatory features. Moreover, we did not
detect significant differences between the response of Mfs cultured from blood
derived monocytes before and after implantation of Ti implants.
PMID- 28501650
TI - PROBer Provides a General Toolkit for Analyzing Sequencing-Based Toeprinting
Assays.
AB - A number of sequencing-based transcriptase drop-off assays have recently been
developed to probe post-transcriptional dynamics of RNA-protein interaction, RNA
structure, and RNA modification. Although these assays survey a diverse set of
epitranscriptomic marks, we use the term toeprinting assays since they share
methodological similarities. Their interpretation is predicated on addressing a
similar computational challenge: how to learn isoform-specific chemical
modification profiles in the face of complex read multi-mapping. We introduce
PROBer, a statistical model and associated software, that addresses this
challenge for the analysis of toeprinting assays. PROBer takes sequencing data as
input and outputs estimated transcript abundances and isoform-specific
modification profiles. Results on both simulated and biological data demonstrate
that PROBer significantly outperforms individual methods tailored for specific
toeprinting assays. Since the space of toeprinting assays is ever expanding and
these assays are likely to be performed and analyzed together, we believe
PROBer's unified data analysis solution will be valuable to the RNA community.
PMID- 28501651
TI - Severity of traumatic injuries predicting psychological outcomes: A surprising
lack of empirical evidence.
AB - Despite widespread beliefs that trauma severity is related to levels of
posttraumatic stress symptoms (PTSS), the empirical evidence to support such
beliefs is lacking. In the current study we examined Injury Severity Score (ISS),
a medical measure of event severity for physical injuries, in a sample of 460
patients admitted to a Level 1 Trauma Center. Results revealed no significant
relationship between ISS and PTSS, depression, pain, and general physical and
mental health at baseline, three months, and six months post-injury. However, at
12 months post-injury, ISS significantly predicted depression, pain, and physical
health, but was unrelated to PTSS. The effect sizes of these relationships were
small and would not remain significant if any adjustments for multiple
comparisons were employed. We conclude that the relationship between ISS and PTSS
is, at best, weak and inconsistent. The results are discussed in the broader
picture of event severity and psychological outcomes.
PMID- 28501652
TI - A new adenovector system for implementing thymulin gene therapy for inflammatory
disorders.
AB - Thymulin is a thymic peptide possessing anti-inflammatory effects. In order to
manipulate thymulin expression in gene therapy studies, we built a bidirectional
regulatable two-vector Tet-Off system and the corresponding control system. The
experimental two-vector system, ETV, consists of a recombinant adenovector (RAd)
harboring an expression cassette centered on a Tet-Off bidirectional promoter
flanked by a synthetic gene for thymulin and the gene for humanized Green
Fluorescent Protein (hGFP). The second adenovector of this system, RAd-tTA,
constitutively expresses the regulatory protein tTA. When cells are co-transduced
by the two adenovector components, tTA activates the bidirectional promoter and
both transgenes are expressed. In the presence of the antibiotic doxycycline
(DOX) transgene expression is deactivated. The control two-vector system, termed
CTV, is similar to ETV but only expresses hGFP. In CHO-K1, BHK, and C2C12 cells,
ETV and CTV induced a dose-dependent hGFP expression. In CHO-K1 cells, transgene
expression was almost completely inhibited by DOX (1mg/ml). After
intracerebroventricular injection of ETV in rats, thymulin levels increased
significantly in the cerebrospinal fluid and there was high hGFP expression in
the ependymal cell layer. When injected intramuscularly the ETV system induced a
progressive increase in serum thymulin levels, which were inhibited when DOX was
added to the drinking water. We conclude that our regulatable two-adenovector
system is an effective molecular tool for implementing short and long-term anti
inflammatory thymulin gene therapy in animal models of acute or chronic
inflammation.
PMID- 28501653
TI - Incorporating wind availability into land use regression modelling of air quality
in mountainous high-density urban environment.
AB - Urban air quality serves as an important function of the quality of urban life.
Land use regression (LUR) modelling of air quality is essential for conducting
health impacts assessment but more challenging in mountainous high-density urban
scenario due to the complexities of the urban environment. In this study, a total
of 21 LUR models are developed for seven kinds of air pollutants (gaseous air
pollutants CO, NO2, NOx, O3, SO2 and particulate air pollutants PM2.5, PM10) with
reference to three different time periods (summertime, wintertime and annual
average of 5-year long-term hourly monitoring data from local air quality
monitoring network) in Hong Kong. Under the mountainous high-density urban
scenario, we improved the traditional LUR modelling method by incorporating wind
availability information into LUR modelling based on surface geomorphometrical
analysis. As a result, 269 independent variables were examined to develop the LUR
models by using the "ADDRESS" independent variable selection method and stepwise
multiple linear regression (MLR). Cross validation has been performed for each
resultant model. The results show that wind-related variables are included in
most of the resultant models as statistically significant independent variables.
Compared with the traditional method, a maximum increase of 20% was achieved in
the prediction performance of annual averaged NO2 concentration level by
incorporating wind-related variables into LUR model development.
PMID- 28501655
TI - Changes of auditory event-related potentials in ovariectomized rats injected with
d-galactose: Protective role of rosmarinic acid.
AB - Rosmarinic acid (RA), which has multiple bioactive properties, might be a useful
agent for protecting central nervous system against age related alterations. In
this context, the purpose of the present study was to investigate possible
protective effects of RA on mismatch negativity (MMN) component of auditory event
related potentials (AERPs) as an indicator of auditory discrimination and echoic
memory in the ovariectomized (OVX) rats injected with d-galactose combined with
neurochemical and histological analyses. Ninety female Wistar rats were randomly
divided into six groups: sham control (S); RA-treated (R); OVX (O); OVX+RA
treated (OR); OVX+d-galactose-treated (OD); OVX+d-galactose+RA-treated (ODR).
Eight weeks later, MMN responses were recorded using the oddball condition. An
amplitude reduction of some components of AERPs was observed due to ovariectomy
with or without d-galactose administiration and these reduction patterns were
diverse for different electrode locations. MMN amplitudes were significantly
lower over temporal and right frontal locations in the O and OD groups versus the
S and R groups, which was accompanied by increased thiobarbituric acid reactive
substances (TBARS) and hydroxy-2-nonenal (4-HNE) levels. RA treatment
significantly increased AERP/MMN amplitudes and lowered the TBARS/4-HNE levels in
the OR and ODR groups versus the O and OD groups, respectively. Our findings
support the potential benefit of RA in the prevention of auditory distortion
related to the estrogen deficiency and d-galactose administration at least partly
by antioxidant actions.
PMID- 28501654
TI - Urinary organophosphate insecticide metabolite concentrations during pregnancy
and children's interpersonal, communication, repetitive, and stereotypic
behaviors at 8 years of age: The home study.
AB - BACKGROUND: Prenatal exposure to organophosphate insecticides may be associated
with autism spectrum disorders and related behaviors. This association may be
modified by single nucleotide polymorphisms in the paraoxonase (PON1) enzyme.
OBJECTIVE: We examined the relationship of prenatal organophosphate insecticide
biomarkers with reciprocal social, repetitive, and stereotypic behaviors in 8
year old children, and modification of this relationship by child PON1
polymorphisms. METHODS: Among 224 pregnant women, we quantified concentrations of
six nonspecific dialkyl phosphate (DAP) metabolites of organophosphate
insecticides in two urine samples collected at ~16 and ~26 weeks gestation. When
children were eight years old, we administered the Social Responsiveness Scale
(SRS), a continuous measure of various dimensions of interpersonal behavior,
communication, and repetitive/stereotypic behaviors. We estimated the association
between a 10-fold increase in the sum of six DAP concentrations (SigmaDAP) and
SRS scores. We examined whether child PON1192 and PON1-108 genotypes modified
this association. RESULTS: After covariate adjustment, SigmaDAP concentrations
were not associated with SRS scores [beta=-1.2; 95% confidence interval (CI):
4.0, 1.6]. Among children with the PON1-108TT genotype, SigmaDAP concentrations
were associated with 2.5-point higher (95% CI: -4.9, 9.8) SRS scores; however,
the association was not different from the 1.8-point decrease (95% CI: -5.8, 2.2)
among children with PON1-108CT/CC genotypes (SigmaDAP * PON1-108 p-value =0.54).
The association between SigmaDAP concentrations and SRS scores was not modified
by PON1192 (SigmaDAP * PON1192 p-value =0.89). CONCLUSIONS: In this cohort,
prenatal urinary DAP concentrations were not associated with children's social
behaviors; these associations were not modified by child PON1 genotype.
PMID- 28501656
TI - Perioperative Outcomes of Open versus Endovascular Repair for Ruptured
Thoracoabdominal Aneurysms.
AB - BACKGROUND: Open aneurysm repair (OAR) remains the gold standard for treating
ruptured thoracoabdominal aortic aneurysms (TAAAs). The aim of our study is to
compare the 30-day postoperative outcomes among patients with ruptured TAAA
undergoing OAR versus endovascular aneurysm repair. METHODS: Using the National
Surgical Quality Improvement Program database (2006-2015), we identified patients
who underwent OAR and endovascular repair for a ruptured TAAA. Postoperative
outcomes of interest included mortality, renal failure, stroke, and
cardiopulmonary complications. The independent impact of repair type on each of
the aforementioned outcomes was examined after robust risk adjustment. RESULTS: A
total of 206 ruptured TAAA repairs were performed [OAR 144 (70%) versus
endovascular 62 (30%)]. The majority of patients were male (53 %) and white
(77%). The comorbidities were similar between the 2 groups. On average, the
operative time of OAR was approximately 3 hr longer than endovascular repair (P <
0.001). The mortality was similar between the 2 groups (OAR 38% versus
endovascular 26%, P = 0.09). Compared with endovascular repair, OAR was
associated with higher rates of renal and pulmonary complications (32% vs. 13%, P
= 0.004; 58% vs. 37%, P = 0.007, respectively). After adjusting for high-risk
patient characteristics, endovascular repair, in comparison with OAR, was
associated with a 66% reduction of pulmonary injury and 70% reduction in renal
failure (odds ratio [OR] 0.34, 95% CI 0.16-0.73, P = 0.005; OR 0.30, 95% CI 0.11
0.82, P = 0.02). CONCLUSIONS: Our study reflects the contemporary outcomes
following the repair of ruptured TAAA. Despite similar mortality, the
endovascular approach was associated with a significant reduction in the risk of
renal failure and pulmonary injury.
PMID- 28501657
TI - Effects of Mentorship on Graduating Vascular Surgery Trainees.
AB - BACKGROUND: Mentorship within surgery, particularly vascular surgery, has not
been extensively evaluated. This study sought to examine mentorship experiences
in graduating vascular trainees (VTs). METHODS: An anonymous electronic survey
examining current mentor relationships, ideal characteristics, academic
productivity, and operative comfort level was emailed to all US graduating 2015
(n = 141) and 2016 (n = 144) VTs during their last year of training. A parallel
survey was emailed to program/associate program directors (PDs) of all US
vascular training programs (n = 169). RESULTS: Surveys were completed by 65 (38%)
PDs and 62 (22%) VTs. Forty-three (69%) VTs identified a mentor with no
difference in frequency of having a mentor noted among gender, type of training
(fellowship/residency), or geographical region. The majority (41/43, 95%)
recognized a vascular surgeon as their mentor; the mentor was assigned to 10 of
43 (23%) trainees and was their PD to 9 of 43 (21%). Ideal mentor
characteristics, identified by VTs using 4-point Likert scales, were
approachability, supportiveness, and accessibility (3.94, 3.76, and 3.74,
respectively), while those of a good mentee were enthusiasm, ethical work, and
commitment (3.79, 3.69, and 3.45, respectively). Trainees scored accessibility,
approachability, compassion, and same gender significantly higher than PDs as
characteristics of ideal mentors (P < 0.05). The majority of PDs thought
mentorship increased access to research opportunities, professional networking,
and job opportunities, but not operative skill (90%, 95%, 65%, and 18%,
respectively). There was no difference between trainees with mentors and those
without in terms of reported academic productivity or operative comfort level.
Vascular fellows reported higher comfort than residents in open abdominal aortic
aneurysm repair (3.32 vs. 2.73, P = 0.006), juxtarenal aneurysm repair (2.8 vs.
2.1, P = 0.02), and aorto-mesenteric bypass (2.57 vs. 1.93, P = 0.03), and
neither group was comfortable performing carotid stenting or fenestrated
endovascular aneurysm repairs. CONCLUSIONS: There is no difference in academic
productivity or case comfort level between surgical trainees with mentors and
those without. Possible benefits identified by PDs and trainees include
professional networking and increased research and job opportunities. Mentors
should be approachable, accessible, supportive, and ethical, while mentees should
be enthusiastic, ethical, committed, and approachable. Vascular fellows feel more
comfortable with open vascular operations than residents, and nether group feels
comfortable with complex endovascular cases. More research is warranted.
PMID- 28501658
TI - Hybridizing the "Sandwich" and "Chimney" Techniques in the Endovascular Repair of
Coarctation of the Aortic Arch and Postcoarctation Ectasia Concomitant with a
Left Subclavian Artery Aneurysm.
AB - Coarctation of aorta is a rare congenital malformation and is usually accompanied
by other cardiac or vascular lesions. In this case, we describe a 51-year-old
patient who presented with coarctation of the aortic arch and postcoarctation
ectasia concomitant with a left subclavian artery aneurysm. Endovascular therapy
included the deployment of an inverted wedge-shaped covered stent inserted by a
long "chimney" stent and another cylinder-covered stent, forming a "sandwich"
like configuration. The symptoms were alleviated after surgery, and no
perioperative or stent-graft-related complications were observed at a 2-year
follow-up.
PMID- 28501659
TI - Influential Factors on the Evaluation of Adamkiewicz Artery Using a 320-Detector
Row Computed Tomography Device.
AB - BACKGROUND: Understanding the difference of Adamkiewicz artery (AKA) presentation
in healthy and diseased subjects, and the influence of atherosclerotic factors
prevalent in aortic disease patients, are important for aortic disease
therapeutic planning. This study used a 320-detector row computed tomography (CT)
device to examine the impact of clinical aspects of AKA identification in
individuals with and without aortic disease. METHODS: Angio-CTs obtained from 115
patients were assessed and the individuals grouped according to the presence or
absence of aortic disease. Datasets were analyzed using OsiriX software, and AKA
was identified by three-dimensional multiplanar reconstruction. RESULTS: The
group without aortic disease (Group A) comprised 32 (52.5%) men and 29 women,
with a mean age of 53.7 +/- 16.8 years. The group with aortic disease (Group B)
comprised 31 (57.4%) men and 23 women, with a mean age of 64.8 +/- 11.6 years.
AKA was identified in 49 (80.3%) participants of Group A and 23 (42.6%)
individuals of Group B (P <= 0.0001). In 53 cases (73.6%), AKA originated on the
left side. AKA was mainly detected on the left side (73.6%), at the level of T10
to T12 (70%). Tobacco smokers, former smokers, and hypertensive patients had
increased odds of having undetected AKA. CONCLUSIONS: Using the method described
and a state of the art 320-detector row CT device, AKA was detected more
frequently among individuals without aortic disease. Thus, aortic disease and
atherosclerotic risk factors hindered AKA detection.
PMID- 28501660
TI - Alcohol Consumption, High-Density Lipoprotein Cholesterol, Antithrombin III, and
Body Mass Index Are Associated with Great Saphenous Vein Reflux in the Thigh.
AB - BACKGROUND: Venous valvular reflux is the main cause of chronic venous
dysfunction. However, the etiology of valvular reflux is not completely
understood. We conducted this study to investigate new risk factors for venous
reflux of the great saphenous vein (GSV) in the thigh. METHODS: We studied 139
consecutive patients (278 legs) who underwent Doppler ultrasonography at our
hospital between March 2015 and February 2016 for leg discomfort with visible
varicosities, edema, skin changes, or venous ulcer in the legs. Continuous
variables included age, body mass index (BMI), hematological and blood chemistry
parameters, smoking (pack-years), and alcohol consumption (days). Nominal
variables included sex, comorbidities, smoking status, alcohol drinking status,
and specific antibodies. The relationship of GSV reflux with pregnancy and number
of children was investigated in 184 legs of 92 patients among 96 female patients.
RESULTS: On logistic regression analysis, independent factors determining GSV
reflux were BMI (B = 0.126, P = 0.012), high-density lipoprotein (HDL)
cholesterol level (B = 0.029, P = 0.025), duration of alcohol consumption (B =
1.237 E-4, P = 0.016), and antithrombin III level (B = -0.036, P = 0.011).
CONCLUSIONS: In this study, the factors determining GSV reflux were higher HDL
cholesterol level, longer duration of alcohol consumption, lower antithrombin III
level, and higher BMI.
PMID- 28501661
TI - Extensive Cerebrovascular and Visceral Artery Dissection and Pseudoaneurysm with
Underlying Segmental Arterial Mediolysis.
AB - Segmental arterial mediolysis (SAM) is a nonatherosclerotic, nonhereditary
vasculopathy that most commonly involves abdominal aortic branches and
predominantly affects middle-age and elderly populations. Lysis of the outer
arterial media results in separation of the media from the adventitia leading to
dissecting aneurysms and/or pseudoaneurysms. We report a unique case of a 47-year
old man who presented with bilateral internal carotid artery dissection followed
by dissections and aneurysms involving multiple visceral arteries. This case
highlights the dramatic manifestation of SAM and discusses the complexity of
decision-making related to this disease including differential diagnoses and
management.
PMID- 28501662
TI - Surgically Treated Pelvic Pain Caused by Nutcracker Syndrome and Worsened by
Cockett Syndrome in a Child.
AB - Nutcracker syndrome is rarely seen in the young. Most of the symptoms regress
during follow-up. Rarely surgical intervention is necessary. This case
presentation is unique for being the first case of nutcracker syndrome and
coexistent Cockett syndrome that is treated with surgical intervention.
PMID- 28501663
TI - Underutilization of Routine Ultrasound Surveillance after Endovascular Aortic
Aneurysm Repair.
AB - BACKGROUND: Since 2009, the Society for Vascular Surgery has advocated annual
surveillance imaging with ultrasound (US) after the first postoperative year for
uncomplicated endovascular aneurysm repairs (EVARs). We sought to describe
diffusion of US into long-term routine surveillance and to estimate potential
cost savings among Medicare beneficiaries after EVAR. METHODS: Using Medicare
claims data, we identified patients receiving EVAR from 2002 to 2010 and included
only those who did not subsequently have reinterventions, late aneurysm-related
complications, or death. We collected all relevant postoperative imaging
(computed tomography [CT] and US) through 2011. Patients with follow-up less than
1 year were excluded. We estimated cost savings with increased use of US after
the first postoperative year. RESULTS: The cohort comprised 24,615 patients with
a mean follow-up of 3.9 +/- 2.3 years. Mean number of images decreased from 2.23
in the first postoperative year to 0.31 in the 10th year. Utilization of US at
the first postoperative year remained low but increased from 15.2% in 2003 to
28.8% in 2011 (P < 0.001). By the 10th postoperative year, the proportion of
patients receiving US increased from 8.2% to 37.8%, while use of CT only remained
high but decreased from 60.8% to 42.1%. Mean cost of surveillance imaging was
$2,132/CT and $234/US. Performing US in 50-75% of patients beginning 1 year after
EVAR would decrease costs by 14-48%/year. This translates to a mean cost savings
of $338-$1135 per imaged patient per year, with an estimated savings to Medicare
of $155 million to $305 million over 10 years. CONCLUSIONS: CT remains the
primary modality of surveillance for up to 10 years after EVAR for patients
without reinterventions or aneurysm-related complications. Increasing the use of
US and decreasing the use of CT would save cost without compromising outcomes.
PMID- 28501664
TI - Systemic Thrombolytic Therapy and Catheter-Directed Fragmentation with Local
Thrombolytic Therapy in Patients with Pulmonary Embolism.
AB - BACKGROUND: The objective was to compare immediate and long-term results of
systemic thrombolytic therapy (STT) and catheter-directed fragmentation (CDF)
with local thrombolytic therapy (LTT) in patients with massive pulmonary embolism
(PE). METHODS: About 209 patients with massive PE (the high risk of early death)
were included in our study. From 2008 till 2010 in the first group (n = 102), STT
was performed. From 2011 till 2013 in the second group (n = 107), CDF with LTT
was carried out. Echocardiography and pulmonary arteriography were performed in
all patients on admission to hospital and in 5 days after treatment. The patients
of both groups were re-examined in 6 months, 1, 2, and 3 years after the
operation. RESULTS: In the first group, there were 5 (4.9%) cases of in-hospital
30-day mortality. In the second group, there was 1 (0.9%) case of in-hospital 30
day mortality (P = 0.08). In the first group, a clinically significant bleeding
was noted in 4 (3.9%) cases, but it caused mortality only in 1 case. In the
second group, the clinically significant bleeding was not found (P = 0.038).
Persistent postembolic pulmonary hypertension (PPPH) in 9.8% cases of patients in
the first group and 2.9% cases of patients in the second group was determined (P
= 0.048). CONCLUSIONS: CDF combined with LTT is an effective minimal invasive
treatment (helped us to reduce significantly the number of bleeding and PPPH
cases), at least in the midterm, in patients with massive PE.
PMID- 28501665
TI - A Dedicated Surveillance Program Improves Compliance with Endovascular Aortic
Aneurysm Repair Follow-up.
AB - BACKGROUND: Current recommendations suggest lifetime follow-up for endovascular
aortic aneurysm repair (EVAR) patients to avoid consequences associated with
endoleak and aneurysm enlargement. Follow-up compliance has been reported between
43% and 92%, with most single-center studies citing successful follow-up
surveillance at less than 60%. We investigated follow-up completeness with a
defined surveillance program and subsequent secondary intervention prevalence
from a single center. METHODS: Our surveillance program notified patients of the
need for follow-up imaging and surgeon review. Data were obtained from
retrospective review of a prospective database, including operative and follow-up
details, follow-up imaging completeness, endoleak incidence, and secondary
intervention prevalence. RESULTS: Five hundred seventeen patients received
elective EVAR from 2005 to 2015. Surveillance was achieved in 425 (82.3%). Mean
number of follow-up studies was 4.2 +/- 2.9 and median time to first follow-up
was 36 days. Four hundred forty-eight patients (86.7%) had freedom from
intervention. Sixty-nine unique patients (13.3%) had 107 secondary interventions.
Median time to first secondary intervention in 69 patients was 476 days. Mean
number of imaging studies for secondary intervention patients was 6.1 +/- 3.9,
compared with mean 3.4 +/- 2.3 for patients without (P < 0.001). Overall
mortality was 24.6% (n = 127), including 32 deaths of unknown cause (6.2%
overall) and 95 of non-EVAR-related causes (18.3%). No aneurysm-related deaths
were reported. CONCLUSIONS: Regular post-EVAR surveillance through a dedicated
program resulted in a high rate of follow-up compliance, 13.3% rate of secondary
intervention, and low aneurysm-related mortality. Careful lifetime surveillance
remains important in long-term care following elective EVAR.
PMID- 28501666
TI - An Unexpectedly High Rate of Thrombophilia Disorders in Patients with Superficial
Vein Thrombosis of the Lower Extremities.
AB - BACKGROUND: Superficial vein thrombosis (SVT) is a common venous condition.
Recent studies have shown that SVT is associated with high frequency of
thromboembolic complications: from 22-37% for deep venous thrombosis and up to
33% for pulmonary embolism. Our goal was to assess the prevalence of major
hereditary and acquired thrombophilic factors in patients with SVT. METHODS:
Sixty-six patients presenting with primary SVT underwent evaluation for
thrombophilia: molecular testing for the factor V Leiden and factor II G20210 A
(prothrombin) mutations, protein C, protein S, antithrombin deficiency, presence
of lupus anticoagulant, as well as anticardiolipin antibody titers. Patients aged
less than 18 years, with confirmed deep vein thrombosis, and pregnant women were
excluded. RESULTS: 95.5% were Caucasian, and 62.1% were female gender. Age ranged
from 21-88 years. Molecular testing showed that 34.2% of patients were
heterozygous for factor V Leiden, 23.6% were heterozygous for the factor II
mutation, 7.8% had antithrombin deficiency, 2.6% had protein S deficiency, and
2.1% had protein C deficiency. CONCLUSIONS: Our study showed that hereditary and
acquired thrombophilias are higher than previously expected and reported.
PMID- 28501667
TI - Update and new insights in encephalitis.
AB - Infectious encephalitis is a rare but severe medical condition resulting from
direct invasion of the brain by viruses, bacteria, fungi or parasites, or
indirect post-infectious immune or inflammatory disorders when the infectious
agent does not cross the blood-brain barrier. Infectious encephalitis cases
represent an interesting and accurate sentinel to follow up on trends in
infectious diseases or to detect emerging infections. Using Pubmed and Embase, we
searched the most relevant publications over the last years. We present here an
update on the important findings and new data recently published about infectious
encephalitis.
PMID- 28501668
TI - Response Adjusted for Days of Antibiotic Risk (RADAR): evaluation of a novel
method to compare strategies to optimize antibiotic use.
AB - OBJECTIVES: The Response Adjusted for Days of Antibiotic Risk (RADAR) statistic
was proposed to improve the efficiency of trials comparing antibiotic stewardship
strategies to optimize antibiotic use. We studied the behaviour of RADAR in a non
inferiority trial in which a beta-lactam monotherapy strategy (n = 656) was non
inferior to fluoroquinolone monotherapy (n = 888) for patients with moderately
severe community-acquired pneumonia. METHODS: Patients were ranked according to
clinical outcome, using five or eight categories, and antibiotic use. RADAR was
calculated as the probability that the beta-lactam group had a more favourable
ranking than the fluoroquinolone group. To investigate the sensitivity of RADAR
to detrimental clinical outcome we simulated increasing rates of 90-day mortality
in the beta-lactam group and performed the RADAR and non-inferiority analysis.
RESULTS: The RADAR of the beta-lactam group compared with the fluoroquinolone
group was 60.3% (95% CI 57.9%-62.7%) using five and 58.4% (95% CI 56.0%-60.9%)
using eight clinical outcome categories, all in favour of beta-lactam. Sample
sizes for RADAR were 38% (250/653) and 89% (580/653) of the non-inferiority
sample size calculation, using five or eight clinical outcome categories,
respectively. With simulated mortality rates, loss of non-inferiority of the beta
lactam group occurred at a relative risk of 1.125 in the conventional analysis,
whereas using RADAR the beta-lactam group lost superiority at a relative risk of
mortality of 1.25 and 1.5, with eight and five clinical outcome categories,
respectively. CONCLUSIONS: RADAR favoured beta-lactam over fluoroquinolone
therapy for community-acquired pneumonia. Although RADAR required fewer patients
than conventional non-inferiority analysis, the statistic was less sensitive to
detrimental outcomes.
PMID- 28501669
TI - An update on bacterial brain abscess in immunocompetent patients.
AB - BACKGROUND: A brain abscess is a focal infection of the brain that begins as a
localized area of cerebritis. In immunocompetent patients, bacteria are
responsible for >95% of brain abscesses, and enter the brain either through
contiguous spread following otitis, sinusitis, neurosurgery, or cranial trauma,
or through haematogenous dissemination. AIMS: To identify recent advances in the
field. SOURCES: We searched Medline and Embase for articles published during
years 2012-2016, with the keywords 'brain' and 'abscess'. CONTENT: The triad of
headache, fever and focal neurological deficit is complete in ~20% of patients on
admission. Brain imaging with contrast-preferentially magnetic resonance imaging
is the reference standard for diagnosis, and should be followed by stereotactic
aspiration of at least one lesion, before the start of any antimicrobials.
Efforts should be made for optimal management of brain abscess samples, for
reliable microbiological documentation. Empirical treatment should cover oral
streptococci (including milleri group), methicillin-susceptible staphylococci,
anaerobes and Enterobacteriaceae. As brain abscesses are frequently
polymicrobial, de-escalation based on microbiological results is safe only when
aspiration samples have been processed optimally, or when primary diagnosis is
endocarditis. Otherwise, many experts advocate for anaerobes coverage even with
no documentation, given the sub-optimal sensitivity of current techniques. A 6
week combination of third-generation cephalosporin and metronidazole will cure
most cases of community-acquired brain abscess in immunocompetent patients.
IMPLICATIONS: Significant advances in brain imaging, minimally invasive
neurosurgery, molecular biology and antibacterial agents have dramatically
improved the prognosis of brain abscess in immunocompetent patients over the last
decades.
PMID- 28501670
TI - Treg-recruiting microspheres prevent inflammation in a murine model of dry eye
disease.
AB - Dry eye disease (DED) is a common ocular disorder affecting millions of
individuals worldwide. The pathology of DED involves the infiltration of CD4+
lymphocytes, leading to tear film instability and destructive inflammation. In
the healthy steady state, a population of immunosuppressive T-cells called
regulatory T-cells (Treg) regulates proliferation of immune cells that would
otherwise lead to a disruption of immunological homeostasis. For this reason, it
has been suggested that Tregs could restore the immunological imbalance in DED.
To this end, one possible approach would be to recruit the body's own, endogenous
Tregs in order to enrich them at the site of inflammation and tissue destruction.
Previously, we have demonstrated a reduction of inflammation and disease symptoms
in models of periodontitis corresponding to recruitment of endogenous Tregs,
which was accomplished by local placement of controlled release systems that
sustain a gradient of the chemokine CCL22, referred to here as Treg-recruiting
microspheres. Given that DED is characterized by a pro-inflammatory environment
resulting in local tissue destruction, we hypothesized that the controlled
release of CCL22 could also recruit Tregs to the ocular surface potentially
mediating inflammation and symptoms of DED. Indeed, data suggest that Treg
recruiting microspheres are capable of overcoming the immunological imbalance of
Tregs and CD4+ IFN-gamma+ cells in the lacrimal gland. Administration of Treg
recruiting microspheres effectively mitigated the symptoms of DED as measured
through a number of outcomes such as tear clearance, goblet cells density and
corneal epithelial integrity, suggesting that recruitment of endogenous Treg can
mitigate inflammation associated with DED.
PMID- 28501671
TI - Multifunctional liposomes delay phenotype progression and prevent memory
impairment in a presymptomatic stage mouse model of Alzheimer disease.
AB - The failure of clinical trials largely focused on mild to moderate stages of
Alzheimer disease has suggested to the scientific community that the
effectiveness of Amyloid-beta (Abeta)-centered treatments should be evaluated
starting as early as possible, well before irreversible brain damage has
occurred. Accordingly, also the preclinical development of new therapies should
be carried out taking into account this suggestion. In the present investigation
we evaluated the efficacy of a treatment with liposomes multifunctionalized for
crossing the blood-brain barrier and targeting Abeta, carried out on young
APP/PS1 Tg mice, taken as a model of pre-symptomatic disease stage. Liposomes
were administered once a week to Tg mice for 7months, starting at the age of
5months and up to the age of 12 when they display AD-like cognitive and brain
biochemical/anatomical features. The treatment prevented the onset of the long
term memory impairment and slowed down the deposition of brain Abeta; at
anatomical level, prevented both ventricle enlargement and entorhinal cortex
thickness reduction, otherwise occurring in untreated mice. Strikingly, these
effects were maintained 3months after treatment discontinuation. An increase of
Abeta levels in the liver was detected at the end of the treatment, then followed
also by reduction of brain Amyloid Precursor Protein and increase of Abeta
degrading enzymes. These results suggest that the treatment promotes brain Abeta
clearance by a peripheral 'sink' effect and ultimately affects Abeta turnover in
the brain. Worth of note, the treatment was apparently not toxic for all the
organs analyzed, in particular for brain, as suggested by the lower brain TNF
alpha and MDA levels, and by higher level of SOD activity in treated mice.
Together, these findings promote a very early treatment with multi-functional
liposomes as a well-tolerated nanomedicine-based approach, potentially suitable
for a disease-modifying therapy of AD, able to delay or prevent relevant features
of the disease.
PMID- 28501672
TI - Combining reactive triblock copolymers with functional cross-linkers: A versatile
pathway to disulfide stabilized-polyplex libraries and their application as pDNA
vaccines.
AB - Therapeutic nucleic acids such as pDNA hold great promise for the treatment of
multiple diseases. These therapeutic interventions are, however, compromised by
the lack of efficient and safe non-viral delivery systems, which guarantee
stability during blood circulation together with high transfection efficiency. To
provide these desired properties within one system, we propose the use of
reactive triblock copolypept(o)ides, which include a stealth-like block for
efficient shielding, a hydrophobic block based on reactive disulfides for cross
linking and a cationic block for complexation of pDNA. After the complexation
step, bifunctional cross-linkers can be employed to bio-reversibly stabilize
derived polyplexes by disulfide bond formation and to introduce endosomolytic
moieties at the same time. Cross-linked polyplexes show no aggregation in human
blood serum. Upon cellular uptake and cleavage of disulfide bonds, the cross
linkers can interact with the endosomal membrane, leading to lysis and efficient
endosomal translocation. In principal, the approach allows for the combination of
one polymer with various different cross-linkers and thus enables the fast
forward creation of a polyplex library. Here, we provide a first insight into the
potential of this concept and use a screening strategy to identify a lead
candidate, which is able to transfect dendritic cells with a model DNA vaccine.
PMID- 28501673
TI - Chemotherapeutic drug-photothermal agent co-self-assembling nanoparticles for
near-infrared fluorescence and photoacoustic dual-modal imaging-guided chemo
photothermal synergistic therapy.
AB - Multimodal imaging-guided synergistic combination therapy has shown great
potential for cancer treatment. However, the nanocarrier-based theranostic
systems suffer from batch-to-batch variation, complexity of multicomponent, poor
drug loading, and carrier-related toxicity issues. To address these issues,
herein we developed a novel carrier-free theranostic system with nanoscale
characteristics for near-infrared fluorescence (NIRF) and photoacoustic (PA) dual
modal imaging-guided synergistic chemo-photothermal therapy (PTT). Indocyanine
green (ICG) and epirubicin (EPI) could co-self-assemble into small molecular
nanoparticles (NPs) in aqueous solution without any molecular precursor or
excipient via collaborative interactions (electrostatic, pi-pi stacking, and
hydrophobic interactions). The exceptionally high dual-drug loading (~92wt%) ICG
EPI NPs showed good physiological stability, preferable photothermal response,
excellent NIRF/PA imaging properties, pH-/photo-responsive drug release behavior,
and promoted cellular endocytosis compared with free ICG or EPI. Importantly, the
ICG-EPI NPs showed excellent tumor targeting ability with high spatial resolution
and deep penetration via in vivo NIRF/PA dual-modal imaging. Moreover, in
comparison with individual chemotherapy or PTT, the combinational chemo-PTT
therapy of ICG-EPI NPs with NIR laser irradiation synergistically induced
apoptosis and death of cancer cells in vitro, and showed synergistic chemo-PTT
efficiency in vivo as evidenced by highly efficient tumor ablation. Furthermore,
the ICG-EPI NPs exhibited inappreciable toxicity. This co-self-assembly of both
FDA-approved agents provides a safe and "Molecular economical" strategy in the
rational design of multifunctional nano-theranostic systems for real-time self
monitoring intracellular drug delivery and targeting multimodal imaging-guided
synergistic combination therapy.
PMID- 28501674
TI - Target attainment with continuous dosing of piperacillin/tazobactam in critical
illness: a prospective observational study.
AB - Optimal dosing of beta-lactam antibiotics in critically ill patients is a
challenge given the unpredictable pharmacokinetic profile of this patient
population. Several studies have shown intermittent dosing to often yield
inadequate drug concentrations. Continuous dosing is an attractive alternative
from a pharmacodynamic point of view. This study evaluated whether, during
continuous dosing, piperacillin concentrations reached and maintained a pre
defined target in critically ill patients. Adult patients treated with
piperacillin by continuous dosing in the intensive care unit of a university
medical centre in The Netherlands were prospectively studied. Total and unbound
piperacillin concentrations drawn at fixed time points throughout the entire
treatment course were determined by liquid chromatography-tandem mass
spectrometry. A pharmacokinetic combined target of a piperacillin concentration
>=80 mg/L, reached within 1 h of starting study treatment and maintained
throughout the treatment course, was set. Eighteen patients were analysed. The
median duration of monitored piperacillin treatment was 60 h (interquartile
range, 33-96 h). Of the 18 patients, 5 (27.8%) reached the combined target; 15
(83.3%) reached and maintained a less strict target of >16 mg/L. In this patient
cohort, this dosing schedule was insufficient to reach the pre-defined target.
Depending on which target is to be met, a larger initial cumulative dose is
desirable, combined with therapeutic drug monitoring.
PMID- 28501675
TI - Predicting heavy episodic drinking using an extended temporal self-regulation
theory.
AB - INTRODUCTION: Alcohol consumption contributes significantly to the global burden
from disease and injury, and specific patterns of heavy episodic drinking
contribute uniquely to this burden. Temporal self-regulation theory and the dual
process model describe similar theoretical constructs that might predict heavy
episodic drinking. The aims of this study were to test the utility of temporal
self-regulation theory in predicting heavy episodic drinking, and examine whether
the theoretical relationships suggested by the dual-process model significantly
extend temporal self-regulation theory. METHODS: This was a predictive study with
149 Australian adults. Measures were questionnaires (self-report habit index,
cues to action scale, purpose-made intention questionnaire, timeline follow-back
questionnaire) and executive function tasks (Stroop, Tower of London, operation
span). Participants completed measures of theoretical constructs at baseline and
reported their alcohol consumption two weeks later. Data were analysed using
hierarchical multiple linear regression. RESULTS: Temporal self-regulation theory
significantly predicted heavy episodic drinking (R2=48.0-54.8%, p<0.001) and the
hypothesised extension significantly improved the prediction of heavy episodic
drinking frequency (DeltaR2=4.5%, p=0.001) but not peak consumption
(DeltaR2=1.4%, p=0.181). Intention and behavioural prepotency directly predicted
heavy episodic drinking (p<0.01). Planning ability moderated the intention
behaviour relationship and inhibitory control moderated the behavioural
prepotency-behaviour relationship (p<0.05). CONCLUSIONS: Both temporal self
regulation theory and the extended temporal self-regulation theory provide good
prediction of heavy episodic drinking. Intention, behavioural prepotency,
planning ability and inhibitory control may be good targets for interventions
designed to decrease heavy episodic drinking.
PMID- 28501676
TI - Does the implementation of evidence-based and culturally competent practices
reduce disparities in addiction treatment outcomes?
AB - RATIONALE: Research is limited on the extent to which implementation of evidence
based and culturally responsive practices reduces outcome disparities in
substance use disorder treatment. We examined the role of contingency management
treatment (CMT), medication-assisted treatment (MAT), and culturally competent
practices on Mexican Americans' rate of successful completion of treatment.
METHODS: We analyzed a concatenated dataset from 153 publicly funded substance
use disorder treatment programs in Los Angeles County, California, in 2011 and
2013. These data were merged with data from 15,412 adult clients in both periods,
of whom we selected only Mexican Americans (46.3%) and non-Latino Whites (53.7%).
The outcome was successful treatment completion. The main independent variables
were client demographics, drug use severity, mental health issues, and program
license and professional accreditation. RESULTS: Less than half of the programs
highly implemented CMT, MAT, and culturally competent practices. CMT and cultural
competence were not associated with successful treatment completion. However,
Mexican Americans in programs with high degree of implementation of MAT had
higher odds of successfully completing treatment compared to non-Latino Whites
and programs with low MAT (OR=1.389; 95% CI=1.018, 1.897). CONCLUSIONS: Findings
highlight the role of MAT in reducing the disparity in treatment completion
between Mexican Americans and non-Latino Whites. Implications for health policy
and the dissemination of MAT are discussed.
PMID- 28501677
TI - Modeling variability in air pollution-related health damages from individual
airport emissions.
AB - In this study, we modeled concentrations of fine particulate matter (PM2.5) and
ozone (O3) attributable to precursor emissions from individual airports in the
United States, developing airport-specific health damage functions (deaths per
1000t of precursor emissions) and physically-interpretable regression models to
explain variability in these functions. We applied the Community Multiscale Air
Quality model using the Decoupled Direct Method to isolate PM2.5- or O3-related
contributions from precursor pollutants emitted by 66 individual airports. We
linked airport- and pollutant-specific concentrations with population data and
literature-based concentration-response functions to create health damage
functions. Deaths per 1000t of primary PM2.5 emissions ranged from 3 to 160
across airports, with variability explained by population patterns within 500km
of the airport. Deaths per 1000t of precursors for secondary PM2.5 varied across
airports from 0.1 to 2.7 for NOx, 0.06 to 2.9 for SO2, and 0.06 to 11 for VOCs,
with variability explained by population patterns and ambient concentrations
influencing particle formation. Deaths per 1000t of O3 precursors ranged from
0.004 to 1.0 for NOx and 0.03 to 1.5 for VOCs, with strong seasonality and
influence of ambient concentrations. Our findings reinforce the importance of
location- and source-specific health damage functions in design of health
maximizing emissions control policies.
PMID- 28501678
TI - The risk of venous thromboembolism with aspirin compared to anticoagulants after
hip and knee arthroplasty.
AB - BACKGROUND: Recent guidelines include aspirin as an option to prevent venous
thromboembolism (VTE) in selected patients undergoing hip or knee replacement
surgery. However, the efficacy of aspirin after arthroplasty has not been well
defined, particularly in more contemporary patient populations. We compared rates
of post-operative VTE between patients who received aspirin-only versus
anticoagulants after hip or knee arthroplasty, using data from a large US-based
administrative database. MATERIALS AND METHODS: We conducted a retrospective
cohort study of 231,780 adults who underwent total knee arthroplasty and 110,621
who underwent total hip arthroplasty in 2009-2012 and who received pharmacologic
VTE prophylaxis (aspirin or anticoagulant) within the first 7days after surgery.
We compared the risk of post-operative VTE between patients receiving aspirin
only vs. anticoagulants, controlling for clinical and hospital characteristics
using multivariable logistic regression with propensity score adjustment.
RESULTS: Aspirin-only prophylaxis was administered to 7.5% of patients after knee
arthroplasty and 8.0% after hip arthroplasty. Post-operative VTE was diagnosed in
2217 (0.96%) patients after knee arthroplasty and 454 (0.41%) after hip
arthroplasty. Compared to anticoagulants, aspirin was not associated with a
higher risk for post-operative VTE either after knee arthroplasty (adjusted odds
ratio and 95% confidence interval [OR] 0.34 [0.24-0.48]) or hip arthroplasty (OR
0.82 [0.45-1.51]). CONCLUSIONS: Aspirin was uncommonly administered as the sole
prophylactic agent after hip or knee arthroplasty in this study. However,
patients who received aspirin-only had similar rates of post-operative VTE
compared to patients who received anticoagulants. Further research should focus
on distinguishing which patients benefit more from anticoagulants versus aspirin
after arthroplasty.
PMID- 28501679
TI - Factor structure and longitudinal measurement invariance of PHQ-9 for specialist
mental health care patients with persistent major depressive disorder:
Exploratory Structural Equation Modelling.
AB - BACKGROUND: The Patient Health Questionnaire-9 (PHQ-9) is a widely used
instrument for measuring levels of depression in patients in clinical practice
and academic research; its factor structure has been investigated in various
samples, with limited evidence of measurement equivalence/invariance (ME/I) but
not in patients with more severe depression of long duration. This study aims to
explore the factor structure of the PHQ-9 and the ME/I between treatment groups
over time for these patients. METHODS: 187 secondary care patients with
persistent major depressive disorder (PMDD) were recruited to a randomised
controlled trial (RCT) with allocation to either a specialist depression team arm
or a general mental health arm; their PHQ-9 score was measured at baseline, 3, 6,
9 and 12 months. Exploratory Structural Equational Modelling (ESEM) was performed
to examine the factor structure for this specific patient group. ME/I between
treatment arm at and across follow-up time were further explored by means of
multiple-group ESEM approach using the best-fitted factor structure. RESULTS: A
two-factor structure was evidenced (somatic and affective factor). This two
factor structure had strong factorial invariance between the treatment groups at
and across follow up times. LIMITATIONS: Participants were largely white British
in a RCT with 40% attrition potentially limiting the study's generalisability.
Not all two-factor modelling criteria were met at every time-point. CONCLUSION:
PHQ-9 has a two-factor structure for PMDD patients, with strong measurement
invariance between treatment groups at and across follow-up time, demonstrating
its validity for RCTs and prospective longitudinal studies in chronic moderate to
severe depression.
PMID- 28501680
TI - Dilated Virchow-Robin spaces in the hippocampus impact behaviors and effects of
anti-depressant treatment in model of depressed rats.
AB - The occurrences of dilated Virchow-Robin spaces (dVRSs) and inflammatory factors
were closely related with development of depression and antidepressants. The
present study indicated accumulation of inflammatory factors in dVRSs played a
practical role in behaviors and the treatment-resistant in rats with depression.
Eighty-one male Wistar rats were exposed to chronic unpredictable mild stress
(CUMS) until the model was successfully established. According to the detection
of dVRSs on 7 T structural magnetic resonance imaging (MRI), rats were divided
into two groups (45 CUMSnon-dVRSs rats and 36 CUMSdVRSs rats). Subsequently,
different antidepressant treatment (nontreat, aspirin, fluoxetine,
fluoxetine+aspirin) was given to the two groups, respectively. Sucrose preference
test (SPT), forced swim test (FST) and morris water maze (MWM) was used to test
the behaviors of rats. ELISA and Western blot was used to determine the levels of
inflammatory factors. Compared with the negative control (NC) group, there were
obvious behavioral abnormalities and increased inflammatory factors in the
CUMSnon-dVRSs rats. Interestingly, these changes were more significant in the
CUMSdVRSs rats. In addition, the efficacy of fluoxetine was only found in CUMSnon
dVRSs rats rather than CUMSdVRSs rats. Meanwhile, behaviors and levels of
inflammatory factor in hippocampus were ameliorated in the aspirin group of
CUMSdVRSs rats, and these effects were significantly enhanced in the
fluoxetine+aspirin group. The dVRSs in the hippocampus might exacerbate
depression-like behaviors and the effects of antidepressant treatment in
depressed rats by increasing the levels of inflammatory factors.
PMID- 28501681
TI - Postnatal paternal involvement and maternal emotional disturbances: The effect of
maternal employment status.
AB - BACKGROUND: Recently, studies have begun emphasizing paternal involvement during
the perinatal period and its impact on maternal health. However, most studies
have assessed maternal perception and focused on adolescents or minority groups
in Western countries. Therefore, the current study investigated the association
between paternal involvement and maternal postnatal depression and anxiety, along
with the effects of maternal job status in the Asian society of Taiwan. METHODS:
This study recruited pregnant women in the first trimester of pregnancy as well
as their partners on prenatal visits from July 2011 to September 2013 at four
selected hospitals in metropolitan areas of Taipei, Taiwan. In total, 593
parental pairs completed the first interview and responded to the follow-up
questionnaires until 6 months postpartum. Self-reported data were collected, and
multiple logistic regression models were used for analyses. RESULTS: Lower
paternal childcare and nursing frequency was independently associated with an
increased risk of maternal postpartum depression (adjusted odds ratio (OR) =4.33,
95% confidence interval (CI)=1.34-13.98), particularly among unemployed mothers.
Furthermore, among unemployed mothers, the risk of postnatal anxiety was 3.14
times higher in couples with fathers spending less time with the child, compared
with couples with fathers spending more time (95% CI=1.10-8.98). However, no
significant findings were obtained for employed mothers. CONCLUSIONS: The high
prevalence of maternal postnatal emotional disturbances warrants continual
consideration. Higher paternal involvement in childcare arrangements should be
emphasized to aid in ameliorating these maternal emotional disturbances,
particularly among unemployed mothers.
PMID- 28501682
TI - The role of arachidonic acid/cyclooxygenase cascade, phosphodiesterase IV and Rho
kinase in H2S-induced relaxation in the mouse corpus cavernosum.
AB - BACKGROUND: Penile corpus cavernosum is an extremely vascularized tissue and
cavernosal smooth muscle tone is regulated by the balance between contractile and
relaxant factor. We investigated the possible role of arachidonic
acid/cyclooxygenase cascade, phosphodiesterase IV (PDEIV) and Rho-kinase in
exogenous hydrogen sulfide (H2S)-induced relaxation in mouse corpus cavernosum.
METHODS: The relaxant response to H2S (NaHS as exogenous H2S; 1-1000MUM) were
obtained in isolated mouse corpus cavernosum tissues which pre-contracted by
phenylephrine (5MUM). The effects of 4-(4-octadecylphenyl)-4-oxobutenoic acid
(OBAA; 10MUM), a selective phospholipase A2 (PLA2) inhibitor, indomethacin
(1MUM), a non-selective cyclooxygenase (COX) inhibitor, baicalein (10MUM), a
lipoxygenase (LOX) inhibitor, and proadifen (10MUM), cytochrome P450 inhibitor,
on the relaxant responses to H2S were investigated. Furthermore, the effects of
theophylline (500MUM) and rolipram (1MUM), a non-selective and selective PDEIV
inhibitor, and fasudil (3MUM), a specific Rho-kinase inhibitor, were studied on
H2S-induced relaxation. RESULTS: H2S-induced relaxations were significantly
reduced by OBAA, indomethacin and proadifen but not baicalein. Furthermore,
theophylline, rolipram and fasudil reduced H2S-induced relaxations. CONCLUSION:
These results suggest that PLA2, COX, cytochrome P450, PDEIV and Rho-kinase
pathway may involve in H2S-induced relaxation in mouse corpus cavernosum tissues.
PMID- 28501683
TI - Efficiency of an upflow anaerobic sludge blanket reactor treating potato starch
processing wastewater and related process kinetics, functional microbial
community and sludge morphology.
AB - Herein, an upflow anaerobic sludge blanket reactor was employed to treat potato
starch processing wastewater and the efficacy, kinetics, microbial diversity and
morphology of sludge granules were investigated. When organic loading rate (OLR)
ranging from 2.70 to 13.27kgCOD/m3.d was implemented with various hydraulic
retention times (72h, 48h and 36h), COD removal could reach 92.0-97.7%. Highest
COD removal (97.7%) was noticed when OLR was 3.65kgCOD/m3.d, but had declined to
92.0% when OLR was elevated to 13.27kgCOD/m3.d. Methane and biogas production
increased from 0.48 to 2.97L/L.d and 0.90 to 4.28L/L.d, respectively. Kinetics
and predictions by modified-Gompertz model agreed better with experimental data
as opposed to first-order kinetic model. Functional population with highest
abundance was Chloroflexi (28.91%) followed by Euryarchaeota (22.13%), Firmicutes
(16.7%), Proteobacteria (16.25%) and Bacteroidetes (7.73%). Compared with top
sludge, tightly-bound extracellular polymeric substances was high within bottom
and middle sludge. Morphology was predominantly Methanosaeta-like cells,
Methanosarcina-like cells, rods and cocci colonies.
PMID- 28501684
TI - Ultrasonic hyperactivation of cellulase immobilized on magnetic nanoparticles.
AB - In the present work, effect of low power, low frequency ultrasound on cellulase
immobilized magnetic nanoparticles (cellulase@MNPs) was studied. To gain maximum
activity recovery in cellulase@MNPs various parameters viz. ratio of
MNPs:cellulase, concentration of glutaraldehyde and cross-linking time were
optimized. The influence of ultrasonic power on cellulase@MNPs was studied. Under
ultrasonic conditions at 24kHz, 6W power, and 6min of incubation time there was
almost 3.6 fold increased in the catalytic activity of immobilized cellulase over
the control. Results also indicated that there was improvement in pH and
temperature stability of cellulase@MNPs. Furthermore, thermal deactivation energy
required was more in cellulase@MNPs than that of the free cellulase. Secondary
structural analysis revealed that there were conformational changes in free
cellulase and cellulase@MNPs before and after sonication which might be
responsible for enhanced activity after ultrasonication. Finally, the influence
of ultrasound and cellulase@MNPs for biomass hydrolysis was studied.
PMID- 28501685
TI - Lipid for biodiesel production from attached growth Chlorella vulgaris biomass
cultivating in fluidized bed bioreactor packed with polyurethane foam material.
AB - The potential to grow attached microalgae Chlorella vulgaris in fluidized bed
bioreactor was materialized in this study, targeting to ease the harvesting
process prior to biodiesel production. The proposed thermodynamic mechanism and
physical property assessment of various support materials verified polyurethane
to be suitable material favouring the spontaneous adhesion by microalgae cells.
The 1-L bioreactor packed with only 2.4% (v/v) of 1.00-mL polyurethane foam cubes
could achieve the highest attached growth microalgae biomass and lipid weights of
812+/-122 and 376+/-37mg, respectively, in comparison with other cube sizes. The
maturity of attached growth microalgae biomass for harvesting could also be
determined from the growth trend of suspended microalgae biomass. Analysis of
FAME composition revealed that the harvested microalgae biomass was dominated by
C16-C18 (>60%) and mixture of saturated and mono-unsaturated fatty acids (>65%),
satiating the biodiesel standard with adequate cold flow property and oxidative
stability.
PMID- 28501686
TI - Immobilisation on mesoporous silica and solvent rinsing improve the
transesterification abilities of feruloyl esterases from Myceliophthora
thermophila.
AB - The immobilisation of four feruloyl esterases (FAEs) (FaeA1, FaeA2, FaeB1, FaeB2)
from the thermophilic fungus Myceliophthora thermophila C1 was studied and
optimised via physical adsorption onto various mesoporous silica particles with
pore diameters varying from 6.6nm to 10.9nm. Using crude enzyme preparations,
enrichment of immobilised FAEs was observed, depending on pore diameter and
protein size. The immobilised enzymes were successfully used for the synthesis of
butyl ferulate through transesterification of methyl ferulate with 1-butanol.
Although the highest butyl ferulate yields were obtained with free enzyme, the
synthesis-to-hydrolysis ratio was higher when using immobilised enzymes. Over 90%
of the initial activity was observed in a reusability experiment after nine
reaction cycles, each lasting 24h. Rinsing with solvent to remove water from the
immobilised enzymes further improved their activity. This study demonstrates the
suitability of immobilised crude enzyme preparations in the development of
biocatalysts for esterification reactions.
PMID- 28501687
TI - The effects of combined agricultural phytohormones on the growth, carbon
partitioning and cell morphology of two screened algae.
AB - Applying phytohormones has been considered a promising way to increase lipid
productivity of microalgae recently. Eight dosages of auxin phytohormones were
tested to exploit the effects and mechanism of such stimulants on microalgae. The
optimal one was 20mgL-1, leading to an increase in biomass concentration of 59.3%
for Scenedesmus sp. SDEC-8 and 76.6% for Chlorella sorokiniana SDEC-18, meanwhile
the lipid content rose from 18.74% to 56.17% (SDEC-8) and from 19.69% to 55.76%
(SDEC-18). Proton pumps were activated by the stimulants, causing excretion of
H+, which resulted in pH decline and a favorable condition for growth. Pigments
changes implied that hormones strengthened the dark reactions of photosynthesis.
Auxin addition led to a 3MUm increase in diameter for C. sorokiniana SDEC-18 and
altered the cellular pattern of Scenedesmus sp. SDEC-8, which improved the cells
elongation. Therefore, supplement of auxin phytohormones simultaneously increased
the viability and lipid production of microalgae.
PMID- 28501688
TI - Influence of pre-treatment on torrefaction of Phyllostachys edulis.
AB - This study investigated the effects of different pre-treatments on structural
changes in Phyllostachys edulis. Samples were pretreated with water, 15% ammonia
water, 2% sulfuric acid, hydrothermal carbonization, and ball milling. Moreover,
ultrasound was introduced. The influence of pre-treatment on the physiochemical
property and composition of P. edulis were studied. Moreover, torrefaction
characterization was performed and the distribution of torrefaction products of
pretreated samples was determined. Results showed that pre-treatment effectively
modified physiochemical structure and the torrefaction property of P. edulis. The
pretreatment reduced the ash content and increased the bio-oil content of the
torrefaction products. Compared with that of the raw material, the residual bio
char content of the pretreated samples decreased by 2-8%, and degradation
temperature of bio-char fluctuated between 365 degrees C and 321 degrees C. The
distribution of bio-oil contents, bio-char, and bio-gas in the torrefaction
products significantly varied with pretreatments methods.
PMID- 28501689
TI - Obtaining titanium dioxide nanoparticles with spherical shape and antimicrobial
properties using M. citrifolia leaves extract by hydrothermal method.
AB - In this work, we synthesized titanium dioxide (TiO2) nanoparticles using leaf
extract of Morinda citrifolia (M. citrifolia) by the advanced hydrothermal
method. The synthesized TiO2 nanoparticles were characterized by X-ray
diffraction (XRD), Fourier transmission infrared (FT-IR), Ultraviolet-visible
diffuse reflectance (UV-Vis DRS), Ultraviolet-visible spectroscopy (UV-Vis),
Raman spectroscopy, and scanning electron microscopy with energy dispersive X-ray
spectroscopy (SEM with EDX) techniques. The XRD major peak at 27.3 degrees
corresponds to the (110) lattice plane of tetragonal rutile TiO2 phase and
average crystalline size of nanoparticles is 10nm. The FT-IR result confirmed
that TiO2 nanoparticles and the presences of very few amount of anthraquinone and
phenolic compounds of the leaf extract. The obtained nanoparticles were also
characterized by UV-Vis DRS absorption spectroscopy and an intense band at 423nm
clearly reveals the formation of nanoparticles. SEM images with EDX spectra
clearly reveal the size of the nanoparticles, between 15 and 19nm in excellent
quasi-spherical shape, by virtue of stabilization (capping) agent. The presence
of elements-titanium and oxygen was verified with EDX spectrum. Furthermore, the
inhibitory activity of green synthesized TiO2 nanoparticles was tested against
human pathogens like Staphylococcus aureus, Escherichia coli, Bacillus subtilis,
Pseudomonas aeruginosa, Candida albicans, and Aspergillus niger by the agar well
diffusion method. The TiO2 nanoparticles exhibited superior antimicrobial
activity against Gram-positive bacteria, demonstrating their antimicrobial value
against pathogenic diseases.
PMID- 28501690
TI - Toxicity estimates for diuron and atrazine for the tropical marine cnidarian
Exaiptasia pallida and in-hospite Symbiodinium spp. using PAM chlorophyll-a
fluorometry.
AB - Effective ecotoxicological risk assessments for herbicides in tropical marine
environments are restricted by a lack of toxicity data, sensitive test methods
and endpoints for relevant species, and this requires rectification. The
symbiotic sea anemone Exaiptasia pallida is a suitable test species, representing
the phylum Cnidaria and allowing for assessments of toxicological responses of
both the animal host and in-hospite Symbiodinium spp. Pulse amplitude modulated
(PAM) chlorophyll-a fluorometry is recognised as a valuable ecotoxicological
tool, and here newly-developed test methods are presented using PAM fluorometry
to measure herbicide effects on photosynthetic efficiency of in-hospite
Symbiodinium spp. Additionally, measurements on healthy laboratory-reared E.
pallida provide baseline data demonstrating the normal effective quantum yield
(EQY) and the maximum electron transport rate (ETRm) for Symbiodinium spp. in the
absence of herbicide stress. Concentration-dependant reductions in the EQY and
ETRm occurred during diuron and atrazine exposures; a mean 48-h EC50 (effective
concentration; 50%) of 8MUg/L of diuron was estimated, however atrazine elicited
a much lower toxicity. Twelve-day exposures to 10-200MUg/L diuron showed that the
greatest EQY effect occurred during the first 48h, with little subsequent change.
However, longer exposures to the lowest diuron treatment (1MUg/L) showed the
lowest EQYs after 96h followed by recovery to control levels within 12d.
Furthermore, asexual reproduction was inhibited during 12-d exposures to diuron,
and 12-d EC50 values of 100 and 132MUg/L were estimated to inhibit successful
reproduction of pedal lacerates and juveniles by 50% respectively. This study
provides much needed data contributions to species sensitivity curves for
development of diuron and atrazine water quality guidelines in tropical marine
environments.
PMID- 28501691
TI - Biosynthesis and characterization of copper oxide nanoparticles and its
anticancer activity on human colon cancer cell lines (HCT-116).
AB - The eco-friendly synthesis of nanoparticles through green route from plant
extracts have renowned a wide range of application in the field of modern
science, due to increased drug efficacy and less toxicity in the nanosized
mediated drug delivery model. In the present study, our research groups have
biosynthesized the stable and cost effective copper oxide nanoparticles (CuO NPs)
from the leaves of (Ormocarpum cochinchinense) O. cochinchinense. The synthesis
of crystalline CuO NPs from the leaf extract of O. cochinchinense were confirmed
by various analytical techniques like UV-Visible Spectroscopy (UV-Vis), Fourier
Transform Infrared Spectroscopy (FT-IR), X-Ray Diffractometer (XRD), Scanning
Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) and Selected
Area Electron Diffraction (SAED) pattern. Further the synthesized CuO NPs were
screened for anticancer activity on human colon cancer cell lines (HCT-116) by
MTT (3-(4,5-dimethyl-2-tiazolyl)-2,5-diphenyl-2-tetrazolium bromide) assay. The
obtained result inferred that the synthesized CuO NPs demonstrated high
anticancer cytotoxicity on human colon cancer cell lines (HCT-116) with IC50
value of 40MUgmL-1 were discussed briefly in this manuscript.
PMID- 28501692
TI - Trans-chalcone added in topical formulation inhibits skin inflammation and
oxidative stress in a model of ultraviolet B radiation skin damage in hairless
mice.
AB - Trans-chalcone (TC) is a common precursor of flavonoids. However, the
pharmacological properties of TC remain to be fully understood. The present study
investigated whether topical formulation containing TC (TFcTC) presents
therapeutic effect in UVB radiation-induced skin damage using disease, enzyme
activity, antioxidant activity, protein and mRNA parameters. Control topical
formulation (CTF) and TFcTC were applied in hairless mice before and after
exposure to UVB radiation. Dorsal skin samples were collected after UVB exposure
to evaluate: i) skin edema (weight) was measured by punch biopsy; ii)
spectrophotometric assays were used to measure myeloperoxidase (MPO) and catalase
activities, ferric (FRAP) and ABTS cation reducing antioxidant power, superoxide
anion production and levels of reduced glutathione (GSH); iii) enzymography was
used to measure matrix metalloproteinase-9 (MMP-9) activity; iv)
chemiluminescence was used to measure the lipid peroxidation (LPO); v) enzyme
linked immunosorbent assay (ELISA) was used to measure tumor necrosis factor
alpha (TNF-alpha) levels; vi) reverse transcription quantitative PCR (RT-qPCR)
was used to measure cyclooxygenase-2 (COX-2), gp91phox (NADPH oxidase sub-unity),
glutathione peroxidase-1 (Gpx1), glutathione reductase (Gr), nuclear factor
erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) mRNA expression.
TFcTC inhibited UVB-induced skin edema, MPO activity, MMP-9 activity, TNF-alpha
production, and COX-2 mRNA expression. TFcTC inhibited UVB-induced LPO, down
regulated superoxide anion levels and gp91phox mRNA expression, and improved
antioxidant potential and GSH skin levels. The mRNA expression of detoxification
systems such as Nrf2, HO-1, Gpx1 and Gr, and catalase activity were also enhanced
by treatment with TFcTC. In conclusion, TFcTC protects mice skin from UVB
radiation by inhibiting inflammation, and improving antioxidant and
detoxification systems. Therefore, topical treatment with TC is a novel
therapeutic approach for the treatment of UVB radiation skin damages, which
merits further pre-clinical and clinical investigation.
PMID- 28501694
TI - 4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid attenuates spontaneous
recurrent seizures and vasogenic edema following lithium-pilocarpine induced
status epilepticus.
AB - Vasogenic edema induced by blood brain barrier disruption and neuronal loss play
an important role in the epileptogenic process. 4,4'- diisothiocyanatostilbene
2,2'-disulfonic acid (DIDS) is a commonly used anion channel inhibitor that has
been reported to exert an anticonvulsant effect in rat hippocampus in vitro. The
present study aimed to investigate whether DIDS could prevent epileptogenic
process in rat lithium-pilocarpine model of temporal lobe epilepsy. The tight
junction proteins and serum extravasation were examined in the piriform cortex
3days after status epilepticus. The findings showed that status epilepticus
induced vasogenic edema. Based on these findings, rats were
intracerebroventricularly infused with saline and DIDS 1 week after surgery, DIDS
reduced vasogenic edema and prevented neuronal loss following status epilepticus
in the piriform cortex. Moreover, spontaneous recurrent seizures were recorded by
continuous video monitoring. DIDS significantly reduced the frequency and
duration of spontaneous recurrent seizures from day 28 to day 42 post status
epilepticus. These findings demonstrated that DIDS attenuated vasogenic edema and
neuronal apoptosis and might exert disease-modifying effect in animal model of
temporal lobe epilepsy. These results explored a novel therapeutic strategy for
treatment of epilepsy.
PMID- 28501693
TI - Necrostatin-1 protects hippocampal neurons against ischemia/reperfusion injury
via the RIP3/DAXX signaling pathway in rats.
AB - Global cerebral ischemia/reperfusion (I/R) induces selective neuronal injury in
CA1 region of hippocampus, leading to severe impairment in behavior, learning and
memory functions. However, the molecular mechanism underlying the processes was
not elucidated clearly. RIP3 is a key molecular switch connecting apoptosis,
necrosis and necroptosis. DAXX, as a novel substrate of RIP3, plays a vital role
in ischemia-induced neuronal death. The aim of this study is to investigate the
role and mechanism of RIP3/DAXX signaling pathway on neurons in CA1 region of the
rat hippocampus after cerebral I/R. Global cerebral ischemia was induced by the
method of four-vessel occlusion. RIP1 specific inhibitor Necrostatin-1 was
administered by intracerebroventricular injection 1h before ischemia. Open-field,
closed-field, and Morris water maze tests were performed respectively to examine
the anxiety and cognitive behavior in each group. Hematoxylin and eosinstaining
was used to examine the survival of hippocampal CA1 pyramidal neurons. Western
blot or immunoprecipitation were carried to detect protein expression,
phosphorylation, and interaction. We found that pre-treatment with Nec-1
protected locomotive ability, relieved anxiety behavior, and improved cognitive
ability in the rats subjected to cerebral I/R. In addition Moreover, Nec-1
decreased significantly the dead rate of neurons in hippocampal CA1 region after
cerebral I/R through suppressing RIP1-RIP3 interaction and RIP3 activation along
with RIP3-DAXX interaction, and then blocked DAXX translocation from nucleaus to
cytoplasm, which resulted in the inactiviation of DAXX. We concluded that pre
treatment with Nec-1 can protect neurons in the hippocampal CA1 region against
ischemic damage through the RIP3-DAXX signaling pathway.
PMID- 28501696
TI - The role of nitric oxide in anticonvulsant effect of nanocurcumine on
pentylenetetrazole-induced seizure in mice.
AB - : A plant alkaloid obtained from Curcuma longa, curcumin possesses anti-oxidant
and anti-inflammatory effects. Nanoformulations have been developed for
preclinical studies which demonstrate enhanced therapeutic efficacy. Effect of
acute intraperitoneal (i.p.) administration of curcumin C3 complex nanoparticles
[1,5, 10, 20, 40, 80mg/kg, (i.p.)] 75min prior to PTZ, on clonic seizure
thresholds induced by intravenous infusion of pentylenetetrazole (PTZ) 0.5% was
investigated in comparison with curcumin (40 and 80mg/kg, i.p.) in male mice.
Moreover, to clarify the probable role of NO in the anticonvulsant property of
nanocurcumin, non-effective doses of l-arginine (l-Arg), a NO donor; 7
nitroindazole, 7-NI, a preferential neuronal NO synthase inhibitor; L-NAME, a non
selective NO synthase inhibitor and aminoguanidine (AG), a selective inducible NO
synthase inhibitor (iNOS), in combination with nanocurcumin (80mg/kg, i.p.), 15
30min before it were employed. RESULTS: While curcumin did not show any
anticonvulsant effect, nanocurcumin revealed dose-dependent anticonvulsant
property at the doses 20, 40 and 80mg/kg, P<0.01, P<0.01 and P<0.001,
respectively. l-Arg (30 and 60mg/kg) dose-dependently reversed the anticonvulsant
effect of the most effective nanocurcumin dose (80mg/kg), P<0.01 and P<0.001,
respectively. On the other hand, L-NAME (3 and 10mg/kg, i.p.) markedly
potentiated the sub effective dose of nanocurcumin (10mg/kg), P<0.01 and P<0.001,
respectively. Similarly, AG (50 and 100mg/kg, i.p.) profoundly augmented the
seizure thresholds of nanocurcumin (10mg/kg), P<0.01 and P<0.001, respectively.
In addition, 7-NI (10, 30 and 60mg/kg, i.p.) failed to influence the responses.
CONCLUSION: These data may support excess of NO production following PTZ infusion
probably resulting from iNOS source. Consequently, nanocurcumin probably down
regulated NO. To conclude, nanocurcumin showed anticonvulsant effect.
Furthermore, this effect was reversed following l-arginine as an external NO
precursor. However, both the non-selective NOS inhibitor and selective iNOS
inhibitor increased the thresholds. It is evident that nanocurcumin may influence
the seizure thresholds at least in part through a decrease in NO.
PMID- 28501695
TI - Expression of aromatase and estrogen receptors in lumbar motoneurons of mice.
AB - Estrogen exerts protective roles in amyotrophic lateral sclerosis (ALS). However,
the expression of aromatase (ARO) and estrogen receptors (ERs) in the motoneurons
of spinal cord, has not yet been elucidated. By immunohistochemistry, we found
that ARO and ERs were present in the ventral horn of adult mice lumbar spinal
cord, and colocalized with SMI-32, a motoneuron specific marker. Within
motoneurons, we observed that ARO is detected primarily in the cytoplasm, with
fewer ARO in the nucleus; ERalpha and ERbeta mainly localized in the nucleus with
less in the cytoplasm; while GPR30 is located in soma and processes. In
conclusion, we found that ERs and ARO are expressed in the motoneurons of lumbar
spinal cord in adult mice. These findings suggest that estrogen may be useful as
a promising therapeutic agent for prevention of damage and improvement of
locomotor function in ALS.
PMID- 28501697
TI - Intentional binding as a marker of agency across the lifespan.
AB - The feeling of control over actions and their external effects is known as Sense
of Agency (SoAg). People usually have a distinctive SoAg for events caused by
their own actions. However, if the agent is a child or an older person, this
feeling of being responsible for the consequences of an action may differ from
what an adult would feel. The idea would be that children and elderly may have a
reduced SoAg since their frontal lobes are developing or have started to loose
their efficiency. The aim of this study was to elucidate whether the SoAg changes
across lifespan, using the Intentional Binding (i.e., the temporal attraction
between a voluntary action and its sensory consequence) as implicit measure. Data
show that children and elderly are characterized by a reduced SoAg as compared to
adults. These findings provide a fundamental step in the characterization of SoAg
dynamics throughout individuals' lifetime.
PMID- 28501698
TI - Sensorimotor experience in virtual reality enhances sense of agency associated
with an avatar.
PMID- 28501699
TI - The AGES-Reykjavik study atlases: Non-linear multi-spectral template and atlases
for studies of the ageing brain.
AB - Quantitative analyses of brain structures from Magnetic Resonance (MR) image data
are often performed using automatic segmentation algorithms. Many of these
algorithms rely on templates and atlases in a common coordinate space. Most
freely available brain atlases are generated from relatively young individuals
and not always derived from well-defined cohort studies. In this paper, we
introduce a publicly available multi-spectral template with corresponding tissue
probability atlases and regional atlases, optimised to use in studies of ageing
cohorts (mean age 75 +/- 5 years). Furthermore, we provide validation data from a
regional segmentation pipeline to assure the integrity of the dataset.
PMID- 28501700
TI - Automatic online layer separation for vessel enhancement in X-ray angiograms for
percutaneous coronary interventions.
AB - Percutaneous coronary intervention is a minimally invasive procedure that is
usually performed under image guidance using X-ray angiograms in which coronary
arteries are opacified with contrast agent. In X-ray images, 3D objects are
projected on a 2D plane, generating semi-transparent layers that overlap each
other. The overlapping of structures makes robust automatic information
processing of the X-ray images, such as vessel extraction which is highly
relevant to support smart image guidance, challenging. In this paper, we propose
an automatic online layer separation approach that robustly separates
interventional X-ray angiograms into three layers: a breathing layer, a quasi
static layer and a vessel layer that contains information of coronary arteries
and medical instruments. The method uses morphological closing and an online
robust PCA algorithm to separate the three layers. The proposed layer separation
method ran fast and was demonstrated to significantly improve the vessel
visibility in clinical X-ray images and showed better performance than other
related online or prospective approaches. The potential of the proposed approach
was demonstrated by enhancing contrast of vessels in X-ray images with low vessel
contrast, which would facilitate the use of reduced amount of contrast agent to
prevent contrast-induced side effects.
PMID- 28501701
TI - RadB acts in homologous recombination in the archaeon Haloferax volcanii,
consistent with a role as recombination mediator.
AB - Homologous recombination plays a central role in the repair of double-strand DNA
breaks, the restart of stalled replication forks and the generation of genetic
diversity. Regulation of recombination is essential since defects can lead to
genome instability and chromosomal rearrangements. Strand exchange is a key step
of recombination - it is catalysed by RecA in bacteria, Rad51/Dmc1 in eukaryotes
and RadA in archaea. RadB, a paralogue of RadA, is present in many archaeal
species. RadB has previously been proposed to function as a recombination
mediator, assisting in RadA-mediated strand exchange. In this study, we use the
archaeon Haloferax volcanii to provide evidence to support this hypothesis. We
show that RadB is required for efficient recombination and survival following
treatment with DNA-damaging agents, and we identify two point mutations in radA
that suppress the DeltaradB phenotype. Analysis of these point mutations leads us
to propose that the role of RadB is to act as a recombination mediator, which it
does by inducing a conformational change in RadA and thereby promoting its
polymerisation on DNA.
PMID- 28501702
TI - Brown adipose tissue activation by rutin ameliorates polycystic ovary syndrome in
rat.
AB - Polycystic ovary syndrome (PCOS) is a complex endocrinopathy that is
characterized by anovulation, hyperandrogenism and polycystic ovary. However,
there is a lack of effective treatment for PCOS at present because the pathologic
cause of PCOS has not been elucidated. Although it has been known that brown
adipose tissue transplantation ameliorates PCOS by activating endogenous BAT, BAT
transplantation is not applicable in clinic. Therefore, BAT activation with
natural compound could be an effective treatment strategy for PCOS patients.
Here, we found that 3 weeks of rutin (a novel compound for BAT activation)
treatment increased BAT activation, thereby it improved thermogenesis and
systemic insulin sensitivity in dehydroepiandrosterone (DHEA)-induced PCOS rat.
In addition, the expression levels of ovarian steroidogenic enzymes such as
P450C17, aromatase, 3beta-HSD, 17beta-HSD and STAR were up-regulated in rutin
treated PCOS rat. Furthermore, acyclicity and the serum level of luteinizing
hormone were normalized, and a large number of mature ovulated follicle with a
reduction of cystic formation were observed in PCOS rat after rutin treatment.
Finally, rutin treatment surprisingly improved fertility and birth defect in PCOS
rat. Collectively, our results indicate that rutin treatment significantly
improves systemic insulin resistance and ovarian malfunction in PCOS, and our
findings in this study provide a novel therapeutic option for the treatment of
PCOS by activating BAT with rutin.
PMID- 28501703
TI - Xanthohumol, a hop-derived prenylated flavonoid, promotes macrophage reverse
cholesterol transport.
AB - Xanthohumol, a prominent prenyl flavonoid from the hop plant (Humulus lupulus
L.), is suggested to be antiatherogenic since it reportedly increases high
density lipoprotein (HDL) cholesterol levels. It is not clear whether xanthohumol
promotes reverse cholesterol transport (RCT), the most important antiatherogenic
property of HDL; therefore, we investigated the effects of xanthohumol on
macrophage-to-feces RCT using a hamster model as a CETP-expressing species. In
vivo RCT experiments showed that xanthohumol significantly increased fecal
appearance of the tracer derived from intraperitoneally injected [3H]-cholesterol
labeled macrophages. Ex vivo experiments were then employed to investigate the
detailed mechanism by which xanthohumol enhanced RCT. Cholesterol efflux capacity
from macrophages was 1.5-fold higher in xanthohumol-fed hamsters compared with
the control group. In addition, protein expression and lecithin-cholesterol
acyltransferase activity in the HDL fraction were significantly higher in
xanthohumol-fed hamsters compared with the control, suggesting that xanthohumol
promoted HDL maturation. Hepatic transcript analysis revealed that xanthohumol
increased mRNA expression of abcg8 and cyp7a1. In addition, protein expressions
of liver X receptor alpha and bile pump export protein were increased in the
liver by xanthohumol administration when compared with the control, implying that
it stimulated bile acid synthesis and cholesterol excretion to feces. In
conclusion, our data demonstrate that xanthohumol improves RCT in vivo through
cholesterol efflux from macrophages and excretion to feces, leading to
antiatherosclerosis effects. It remains to be elucidated whether enhancement of
RCT by xanthohumol could prove valuable in humans.
PMID- 28501706
TI - Upward counterfactual thinking and depression: A meta-analysis.
AB - This meta-analysis examined the strength of association between upward
counterfactual thinking and depressive symptoms. Forty-two effect sizes from a
pooled sample of 13,168 respondents produced a weighted average effect size of
r=.26, p<.001. Moderator analyses using an expanded set of 96 effect sizes
indicated that upward counterfactuals and regret produced significant positive
effects that were similar in strength. Effects also did not vary as a function of
the theme of the counterfactual-inducing situation or study design (cross
sectional versus longitudinal). Significant effect size heterogeneity was
observed across sample types, methods of assessing upward counterfactual
thinking, and types of depression scale. Significant positive effects were found
in studies that employed samples of bereaved individuals, older adults,
terminally ill patients, or university students, but not adolescent mothers or
mixed samples. Both number-based and Likert-based upward counterfactual thinking
assessments produced significant positive effects, with the latter generating a
larger effect. All depression scales produced significant positive effects,
except for the Psychiatric Epidemiology Research Interview. Research and
theoretical implications are discussed in relation to cognitive theories of
depression and the functional theory of upward counterfactual thinking, and
important gaps in the extant research literature are identified.
PMID- 28501704
TI - Genetic variation in SLC7A2 interacts with calcium and magnesium intakes in
modulating the risk of colorectal polyps.
AB - Solute carrier family 7, member 2 (SLC7A2) gene encodes a protein called cationic
amino acid transporter 2, which mediates the transport of arginine, lysine and
ornithine. l-Arginine is necessary for cancer development and progression,
including an important role in colorectal cancer pathogenesis. Furthermore,
previous studies found that both calcium and magnesium inhibit the transport of
arginine. Thus, calcium, magnesium or calcium:magnesium intake ratio may interact
with polymorphisms in the SLC7A2 gene in association with colorectal cancer. We
conducted a two-phase case-control study within the Tennessee Colorectal Polyps
Study. In the first phase, 23 tagging single-nucleotide polymorphisms in the
SLC7A2 gene were included for 725 colorectal adenoma cases and 755 controls. In
the second phase conducted in an independent set of 607 cases and 2113 controls,
we replicated the significant findings in the first phase. We observed that
rs2720574 significantly interacted with calcium:magnesium intake ratio in
association with odds of adenoma, particularly multiple/advanced adenoma. In the
combined analysis, among those with a calcium:magnesium intake ratio below 2.78,
individuals who carried GC/CC genotypes demonstrated higher odds of adenoma [OR
(95% CI):1.36 (1.11-1.68)] and multiple/advanced adenoma [OR (95% CI): 1.68
(1.28, 2.20)] than those who carried the GG genotype. The P values for
interactions between calcium:magnesium intake ratio and rs2720574 were .002 for
all adenomas and <.001 for multiple/advanced adenoma. Among those with the GG
genotype, a high calcium:magnesium ratio was associated with increased odds of
colorectal adenoma [OR (95% CI): 1.73 (1.27-2.36)] and advanced/multiple adenomas
[1.62 (1.05-2.50)], whereas among those with the GC/CC genotypes, high
calcium:magnesium ratio was related to reduced odds of colorectal adenoma [0.64
(0.42-0.99)] and advanced/multiple adenomas [0.55 (0.31-1.00)].
PMID- 28501705
TI - Doxorubicin delivered by a redox-responsive dasatinib-containing polymeric
prodrug carrier for combination therapy.
AB - Two novel prodrug polymers POEG-b-PSSDas (redox-sensitive) and POEG-b-PCCDas
(redox-insensitive), which consist of poly(oligo(ethylene glycol) methacrylate)
(POEG) hydrophilic blocks and dasatinib (DAS, an oncogenic tyrosine kinases
inhibitor) conjugated hydrophobic blocks, were designed as dual-functional
carriers for codelivery with doxorubicin (DOX). Both carriers retained antitumor
activity of DAS and could form mixed micelles with DOX. Compared to POEG-b-PCCDas
micelles, incorporation of disulfide linkage into POEG-b-PSSDas micelles
facilitated efficient cleavage of DAS from prodrug micelles in tumor
cells/tissues, leading to a higher level of anti-tumor activity in vitro and in
vivo. In addition, DOX-loaded POEG-b-PSSDas micelles exhibited triggered DOX
release under a redox environment (10mM glutathione, GSH), and demonstrated
enhanced cytotoxicity against 4T1.2 and PC3 cell lines compared to DOX and DOX
loaded POEG-b-PCCDas micelles. More importantly, DOX-loaded POEG-b-PSSDas
micelles were more effective in inhibiting the tumor growth and prolonging the
survival rate in an aggressive murine breast cancer model (4T1.2) compared to DOX
loaded POEG-b-PCCDas micelles and a micellar formulation co-loaded with DOX and
DAS. This redox-responsive prodrug micellar system provides an attractive
strategy for effective combination of tumor targeted therapy and traditional
chemotherapy, which warrants further investigation.
PMID- 28501707
TI - Mechanisms of action in mindfulness-based cognitive therapy (MBCT) and
mindfulness-based stress reduction (MBSR) in people with physical and/or
psychological conditions: A systematic review.
AB - BACKGROUND: Recently, there has been an increased interest in studying the
effects of mindfulness-based interventions for people with psychological and
physical problems. However, the mechanisms of action in these interventions that
lead to beneficial physical and psychological outcomes have yet to be clearly
identified. PURPOSE: The aim of this paper is to review, systematically, the
evidence to date on the mechanisms of action in mindfulness interventions in
populations with physical and/or psychological conditions. METHOD: Searches of
seven databases (PsycINFO, Medline (Ovid), Cochrane Central Register of
Controlled Trials, EMBASE, CINAHL, AMED, ClinicalTrials.gov) were undertaken in
June 2014 and July 2015. We evaluated to what extent the studies we identified
met the criteria suggested by Kazdin for establishing mechanisms of action within
a psychological treatment (2007, 2009). RESULTS: We identified four trials
examining mechanisms of mindfulness interventions in those with comorbid
psychological and physical health problems and 14 in those with psychological
conditions. These studies examined a diverse range of potential mechanisms,
including mindfulness and rumination. Of these candidate mechanisms, the most
consistent finding was that greater self-reported change in mindfulness mediated
superior clinical outcomes. However, very few studies fully met the Kazdin
criteria for examining treatment mechanisms. CONCLUSION: There was evidence that
global changes in mindfulness are linked to better outcomes. This evidence
pertained more to interventions targeting psychological rather than physical
health conditions. While there is promising evidence that MBCT/MBSR intervention
effects are mediated by hypothesised mechanisms, there is a lack of
methodological rigour in the field of testing mechanisms of action for both MBCT
and MBSR, which precludes definitive conclusions.
PMID- 28501709
TI - Calcium ion coordinated dexamethasone supramolecular hydrogel as therapeutic
alternative for control of non-infectious uveitis.
AB - : Supramolecular hydrogels formed by the self-assembly of therapeutic agents have
received considerable attention due to their high drug payload and carrier-free
features. Herein, we constructed a dexamethasone sodium phosphate (Dex)
supramolecular hydrogel in combination with Dex and calcium ion (Ca2+) and
further demonstrated its therapeutic efficacy in the control of ocular
inflammation. The developed supramolecular hydrogel was thoroughly characterized
by rheology, TEM, FTIR and XRD. Calcium ions and Dex concentration had a marked
influence on the sol-gel transition behaviour of hydrogel and the proposed Dex
supramolecular hydrogel displayed thixotropic properties. The drug release rate
from Dex supramolecular hydrogel was dependent on the Ca2+ concentration. In
comparison with Dex aqueous solution, single intravitreal injections of Dex
supramolecular hydrogel up to 30MUg/eye were well tolerated without causing
undesirable complications of fundus blood vessel tortuosity and lens opacity, as
indicated by electroretinograms (ERGs), fundus photography and histopathology.
Moreover, the administration by Dex supramolecular hydrogel exhibited a
comparable anti-inflammatory efficacy to native Dex solution on an experimental
autoimmune uveitis (EAU) model induced in Lewis rats with IRBP peptide and the
therapeutic efficacy had in a dosage-dependent manner. Histological observation
and cytokines measurements indicated that both Dex solution and Dex
supramolecular hydrogel (30MUg/eye) treatment could significantly attenuate the
inflammatory response in both anterior and posterior chambers via the
downregulation of Th1 and Th17 effector responses. All these data suggested that
the developed Dex supramolecular hydrogel might be a therapeutic alternative for
non-infectious uveitis with minimal risk of the induction of lens opacity and
fundus blood vessel tortuosity. STATEMENT OF SIGNIFICANCE: A facile ionic cross
linking strategy was exploited to construct a dexamethasone sodium phosphate
(Dex) supramolecular hydrogel composed of Dex and calcium ion. Intravitreal
injection of Dex hydrogel displayed excellent intraocular biocompatibility
without causing the complications of fundus blood vessel tortuosity and lens
opacity. More importantly, the proposed Dex hydrogel exhibited a comparative anti
inflammatory response to native Dex formulation on an experimental autoimmune
uveitis (EAU) model via the downregulation of Th1 and Th17 effector responses.
PMID- 28501710
TI - Carbon nanotube, graphene and boron nitride nanotube reinforced bioactive
ceramics for bone repair.
AB - : The high brittleness and low strength of bioactive ceramics have severely
restricted their application in bone repair despite the fact that they have been
regarded as one of the most promising biomaterials. In the last few years, low
dimensional nanomaterials (LDNs), including carbon nanotubes, graphene and boron
nitride nanotubes, have gained increasing attention owing to their favorable
biocompatibility, large surface specific area and super mechanical properties.
These qualities make LDNs potential nanofillers in reinforcing bioactive
ceramics. In this review, the types, characteristics and applications of the
commonly used LDNs in ceramic composites are summarized. In addition, the
fabrication methods for LDNs/ceramic composites, such as hot pressing, spark
plasma sintering and selective laser sintering, are systematically reviewed and
compared. Emphases are placed on how to obtain the uniform dispersion of LDNs in
a ceramic matrix and maintain the structural stability of LDNs during the high
temperature fabrication process of ceramics. The reinforcing mechanisms of LDNs
in ceramic composites are then discussed in-depth. The in vitro and in vivo
studies of LDNs/ceramic in bone repair are also summarized and discussed.
Finally, new developments and potential applications of LDNs/ceramic composites
are further discussed with reference to experimental and theoretical studies.
STATEMENT OF SIGNIFICANCE: Despite bioactive ceramics having been regarded as
promising biomaterials, their high brittleness and low strength severely restrict
their application in bone scaffolds. In recent years, low-dimensional
nanomaterials (LDNs), including carbon nanotubes, graphene and boron nitride
nanotubes, have shown great potential in reinforcing bioactive ceramics owing to
their unique structures and properties. However, so far it has been difficult to
maintain the structural stability of LDNs during fabrication of LDNs/ceramic
composites, due to the lengthy, high-temperature process involved. This review
presents a comprehensive overview of the developments and applications of LDNs in
bioactive ceramics. The newly-developed fabrication methods for LDNs/ceramic
composites, the reinforcing mechanisms and the in vitro and in vivo performance
of LDNs are also summarized and discussed in detail.
PMID- 28501708
TI - Responsiveness and Minimally Important Differences for 4 Patient-Reported
Outcomes Measurement Information System Short Forms: Physical Function, Pain
Interference, Depression, and Anxiety in Knee Osteoarthritis.
AB - : Patient-Reported Outcomes Measurement Information System (PROMIS) instruments
can provide valid, interpretable measures of health status among adults with
osteoarthritis (OA). However, their ability to detect meaningful change over time
is unknown. We evaluated the responsiveness and minimally important differences
(MIDs) for 4 PROMIS Short Forms: Physical Function, Pain Interference,
Depression, and Anxiety. We analyzed adults with symptomatic knee OA from our
randomized trial comparing Tai Chi and physical therapy. Using baseline and 12
week scores, responsiveness was evaluated according to consensus standards by
testing 6 a priori hypotheses of the correlations between PROMIS and legacy
change scores. Responsiveness was considered high if >=5 hypotheses were
confirmed, and moderate if 3 or 4 were confirmed. MIDs were evaluated according
to prospective change for people achieving previously-established MID on legacy
comparators. The lowest and highest MIDs meeting a priori quality criteria formed
a MID range for each PROMIS Short Form. Among 165 predominantly female (70%) and
white (57%) participants, mean age was 61 years and body mass index was 33.
PROMIS Physical Function had 5 confirmed hypotheses and Pain Interference,
Depression, and Anxiety had 3 or 4. MID ranges were: Depression = 3.0 to 3.1;
Anxiety = 2.3 to 3.4; Physical Function = 1.9 to 2.2; and Pain Interference =
2.35 to 2.4. PROMIS Physical Function has high responsiveness, and Depression,
Anxiety, and Pain Interference have moderate responsiveness among adults with
knee OA. We established the first MIDs for PROMIS in this population, and
provided an important standard of reference to better apply or interpret PROMIS
in future trials or clinical practice. PERSPECTIVE: This study examined whether
PROMIS Short Form instruments (Physical Function, Pain Interference, Depression,
and Anxiety) were able to detect change over time among adults with knee OA, and
provided minimally important change estimates for each measure. This standard of
reference can help apply or interpret these instruments in the future.
PMID- 28501711
TI - Protection of cortex by overlying meninges tissue during dynamic indentation of
the adolescent brain.
AB - : Traumatic brain injury (TBI) has become a recent focus of biomedical research
with a growing international effort targeting material characterization of brain
tissue and simulations of trauma using computer models of the head and brain to
try to elucidate the mechanisms and pathogenesis of TBI. The meninges, a
collagenous protective tri-layer, which encloses the entire brain and spinal cord
has been largely overlooked in these material characterization studies. This has
resulted in a lack of accurate constitutive data for the cranial meninges,
particularly under dynamic conditions such as those experienced during head
impacts. The work presented here addresses this lack of data by providing for the
first time, in situ large deformation material properties of the porcine dura
arachnoid mater composite under dynamic indentation. It is demonstrated that this
tissue is substantially stiffer (shear modulus, MU=19.10+/-8.55kPa) and relaxes
at a slower rate (tau1=0.034+/-0.008s, tau2=0.336+/-0.077s) than the underlying
brain tissue (MU=6.97+/-2.26kPa, tau1=0.021+/-0.007s, tau2=0.199+/-0.036s),
reducing the magnitudes of stress by 250% and 65% for strains that arise during
indentation-type deformations in adolescent brains. STATEMENT OF SIGNIFICANCE: We
present the first mechanical analysis of the protective capacity of the cranial
meninges using in situ micro-indentation techniques. Force-relaxation tests are
performed on in situ meninges and cortex tissue, under large strain dynamic micro
indentation. A quasi-linear viscoelastic model is used subsequently, providing
time-dependent mechanical properties of these neural tissues under loading
conditions comparable to what is experienced in TBI. The reported data highlights
the large differences in mechanical properties between these two tissues. Finite
element simulations of the indentation experiments are also performed to
investigate the protective capacity of the meninges. These simulations show that
the meninges protect the underlying brain tissue by reducing the overall
magnitude of stress by 250% and up to 65% for strains.
PMID- 28501712
TI - 3D bioprinting for drug discovery and development in pharmaceutics.
AB - : Successful launch of a commercial drug requires significant investment of time
and financial resources wherein late-stage failures become a reason for
catastrophic failures in drug discovery. This calls for infusing constant
innovations in technologies, which can give reliable prediction of efficacy, and
more importantly, toxicology of the compound early in the drug discovery process
before clinical trials. Though computational advances have resulted in more
rationale in silico designing, in vitro experimental studies still require
gaining industry confidence and improving in vitro-in vivo correlations. In this
quest, due to their ability to mimic the spatial and chemical attributes of
native tissues, three-dimensional (3D) tissue models have now proven to provide
better results for drug screening compared to traditional two-dimensional (2D)
models. However, in vitro fabrication of living tissues has remained a bottleneck
in realizing the full potential of 3D models. Recent advances in bioprinting
provide a valuable tool to fabricate biomimetic constructs, which can be applied
in different stages of drug discovery research. This paper presents the first
comprehensive review of bioprinting techniques applied for fabrication of 3D
tissue models for pharmaceutical studies. A comparative evaluation of different
bioprinting modalities is performed to assess the performance and ability of
fabricating 3D tissue models for pharmaceutical use as the critical selection of
bioprinting modalities indeed plays a crucial role in efficacy and toxicology
testing of drugs and accelerates the drug development cycle. In addition,
limitations with current tissue models are discussed thoroughly and future
prospects of the role of bioprinting in pharmaceutics are provided to the reader.
STATEMENT OF SIGNIFICANCE: Present advances in tissue biofabrication have crucial
role to play in aiding the pharmaceutical development process achieve its
objectives. Advent of three-dimensional (3D) models, in particular, is viewed
with immense interest by the community due to their ability to mimic in vivo
hierarchical tissue architecture and heterogeneous composition. Successful
realization of 3D models will not only provide greater in vitro-in vivo
correlation compared to the two-dimensional (2D) models, but also eventually
replace pre-clinical animal testing, which has their own shortcomings. Amongst
all fabrication techniques, bioprinting- comprising all the different modalities
(extrusion-, droplet- and laser-based bioprinting), is emerging as the most
viable fabrication technique to create the biomimetic tissue constructs.
Notwithstanding the interest in bioprinting by the pharmaceutical development
researchers, it can be seen that there is a limited availability of comparative
literature which can guide the proper selection of bioprinting processes and
associated considerations, such as the bioink selection for a particular
pharmaceutical study. Thus, this work emphasizes these aspects of bioprinting and
presents them in perspective of differential requirements of different
pharmaceutical studies like in vitro predictive toxicology, high-throughput
screening, drug delivery and tissue-specific efficacies. Moreover, since
bioprinting techniques are mostly applied in regenerative medicine and tissue
engineering, a comparative analysis of similarities and differences are also
expounded to help researchers make informed decisions based on contemporary
literature.
PMID- 28501714
TI - Determination of polymer crystallinity by the multivariable curve resolution
method in 13C solid NMR spectrum.
AB - Most of the polymers are composed of a crystal part, an amorphous part, and a
transitional interfacial part. These components present disparate physical and
chemical characteristics. However, it always suffers from peak overlapping in
solid NMR spectrum in order to acquire polymer's crystallinity. The polyethylene
oxide (PEO) sample was tested using the Torchia pulse sequence combined with the
Multivariate Curve Resolution (MCR) method. A two dimensional CP/MAS spectrum
containing spin-lattice relaxation time (T1) information was acquired. After the
correction based on the reciprocity relation, the overlapped peaks were resolved
and quantified together with their T1's. Crystallinity is therefore observed
naturally according to components' content ratios associated with their T1
values.
PMID- 28501713
TI - An in situ photocrosslinkable platelet rich plasma - Complexed hydrogel glue with
growth factor controlled release ability to promote cartilage defect repair.
AB - : The repair of articular cartilage injury is a great clinical challenge.
Platelet-rich plasma (PRP) has attracted much attention for the repair of
articular cartilage injury, because it contains various growth factors that are
beneficial for wound repair. However, current administration methods of PRP have
many shortcomings, such as unstable biological fixation and burst release of
growth factors, all of which complicate its application in the repair of
articular cartilage and compromise its therapeutic efficacy. In this study, based
on our previously reported photoinduced imine crosslinking (PIC) reaction, we
developed an in situ photocrosslinkable PRP hydrogel glue (HNPRP) through adding
a photoresponsive hyaluronic acid (HA-NB) which could generate aldehyde groups
upon light irradiation and subsequently react with amino groups, into autologous
PRP. Our study showed that HNPRP hydrogel glue was cytocompatible and could be
conveniently and rapidly prepared in situ, forming a robust hydrogel scaffold. In
addition, our results demonstrated that HNPRP hydrogel not only achieved
controlled release of growth factors, but also showed strong tissue adhesive
ability. Therefore, HNPRP hydrogel was quite suitable for cartilage defect
regeneration. Our further in vitro experiment showed that HNPRP hydrogel could
promote the proliferation and migration of chondrocytes and bone marrow stem
cells (BMSCs). In vivo testing using a rabbit full-thickness cartilage defect
model demonstrated that HNPRP hydrogel could achieve integrative hyaline
cartilage regeneration and its therapeutic efficacy was better than thrombin
activated PRP gel. STATEMENT OF SIGNIFICANCE: In this study, we have developed a
photocrosslinkable platelet rich plasma (PRP) - complexed hydrogel glue (HNPRP)
for cartilage regeneration. The in situ formed HNPRP hydrogel glue showed not
only the controlled release ability of growth factors, but also strong tissue
adhesiveness, which could resolve the current problems in clinical application of
PRP. Furthermore, HNPRP hydrogel glue could promote integrative hyaline cartilage
regeneration, and its reparative efficacy for cartilage defect was better than
thrombin activated PRP gel. This study provided not only an effective repair
material for cartilage regeneration, but also developed an advanced method for
PRP application.
PMID- 28501716
TI - Cross-protection in Neisseria meningitidis serogroups Y and W polysaccharides: A
comparative conformational analysis.
AB - The capsular polysaccharide is the main virulence factor in meningococcus. The
capsular polysaccharides for meningococcal serogroups Y and W are almost
identical polymers of hexose-sialic acid, suggesting the possibility of cross
protection between group Y and W vaccines. However, early studies indicated that
they elicit different levels of cross-protection. Here we explore the
conformations of the meningococcal Y and W polysaccharides with molecular
dynamics simulations of three repeating unit oligosaccharide strands. We find
differences in Y and W antigen conformation: the Y polysaccharide has a single
dominant conformation, whereas W exhibits a family of conformations including the
Y conformation. This result is supported by our NMR NOESY analysis, which
indicates key close contacts for W that are not present in Y. These
conformational differences provide an explanation for the different levels of
cross-protection measured for the Y and W monovalent vaccines and the high group
W responses observed in HibMenCY-TT vaccinees.
PMID- 28501715
TI - Mutations in the Hco-mptl-1 gene in a field-derived monepantel-resistant isolate
of Haemonchus contortus.
AB - Resistance to the anthelmintic drug monepantel (Zolvix(r)) has emerged in
parasitic worms infecting sheep and goats. The mechanism of resistance in these
cases is unknown. The drug targets nicotinic acetylcholine receptors belonging to
the nematode-specific DEG-3 subfamily. We examined the receptor gene, Hco-mptl-1,
in a highly Zolvix(r)-resistant and a -susceptible isolate of the parasitic
nematode Haemonchus contortus. cDNA coding for the full length receptor protein
(Hco-MPTL-1) was present in all clones prepared from a pool of susceptible larvae
(21/21 clones) and approximately 50% of those from the resistant isolate (17/33).
On the other hand, the remaining clones from the resistant isolate showed various
mutations that resulted in truncated predicted proteins, missing at least one
transmembrane domain. The most common mutation (11/33 clones) resulted in the
retention of intron 15, a premature stop codon, and a truncated protein.
Sequencing of intron 15 genomic DNA showed very few SNPs in susceptible larvae
and in 12/18 clones from resistant larvae, alongside the presence of at least 17
SNPs in the remaining resistant clones. The present study shows that the highly
resistant isolate has a number of mutations in the drug target gene that would
most-likely result in a non-functional receptor, thus rendering the larvae
insensitive to the drug. The presence of many wild-type sequences in this highly
resistant population suggests that there was a significant presence of
heterozygotes in the survivors of the field drench treatment from which the
isolate was derived, and hence that at least some of the mutations may be
dominant. Alternatively, their presence may be due to the additional influence of
mutations at another locus contributing to the resistance phenotype. The presence
of multiple separate mutations in the Hco-mptl-1 gene in this viable field
derived worm isolate may at least partly explain why resistance to Zolvix(r) has
arisen rapidly in the field.
PMID- 28501717
TI - Assisting asylum seekers in a time of global forced displacement: Five clinical
cases.
AB - According to the United Nations High Commissioner on Refugees, over 65 million
people were displaced from their homes due to conflict and persecution in 2015.
Many physicians express an interest in human rights and a desire to assist this
group of refugees and asylum seekers. Physicians are able to use their unique
skills by performing medical forensic evaluations of individuals seeking asylum.
Some asylum seekers have psychological or physical scars or functional
abnormalities relating to injuries or ill-treatment they experience due to
persecution. Documenting these findings can significantly improve the likelihood
that they will be granted asylum. This manuscript outlines the historical and
legal background of asylum. Each of the individuals presented in this paper
experienced persecution in different forms. One person was tortured due to his
political opinion and one was assaulted because he was gay. One woman sought
asylum due to domestic violence, another woman because she had been subjected to
female genital mutilation/cutting (FGM/C) and the last suffered severe
psychological trauma related to a forced marriage. Five typical clinical cases of
medical forensic evaluations are outlined, each with different forms of
persecution and physical or psychological findings. Physicians have an interest
in using their expertise to help this underserved population. They report that
working with asylum seekers is rewarding, intellectually stimulating and a novel
way to use their training and skills.
PMID- 28501718
TI - Luminescence studies of zinc borates activated with different concentrations of
Ce and La under x-ray and electron excitation.
AB - Several ZnB2O4 powder samples having dopants concentrations of 0.1, 0.01, 0.04wt%
Ce and La were prepared using the nitric acid method via the starting oxides.
Several complementary methods such as powder X-ray diffraction (XRD), thermal
analyses environmental scanning electron microscopy (ESEM), Radioluminescence
(RL) and Cathodoluminescence (CL) techniques were used. Unique luminescence
properties of Ce doped ZnB2O4 powder samples are reported for the first time. A
new luminescence bands appearing in red part of the spectrum and having all the
characteristics of Ce3+ were obtained from RL results. Changing the Ce and La
concentration of 0.01-0.1wt% leads to an increase in RL and CL intensities of
Ce3+ and La3+ ions and also CL emission spectra of ZnB2O4 show gradual shift
towards longer wavelength. When we compare the luminescence intensity of the
samples it is seen that Ce doped ZnB2O4 has the highest intense whereas La doped
ZnB2O4 has the lowest one. However, emission spectra of both Ce and La doped
samples kept unchanged.
PMID- 28501719
TI - Colliding jets provide depth control for water jetting in bone tissue.
AB - In orthopaedic surgery, water jet drilling provides several advantages over
classic drilling with rigid drilling bits, such as the always sharp cut, absence
of thermal damage and increased manoeuvrability. Previous research showed that
the heterogeneity of bone tissue can cause variation in drilling depth whilst
water jet drilling. To improve control over the drilling depth, a new method is
tested consisting of two water jets that collide directly below the bone surface.
The expected working principle is that after collision the jets will
disintegrate, with the result of eliminating the destructive power of the
coherent jets and leaving the bone tissue underneath the focal point intact. To
assess the working principle of colliding water jets (CWJ), the influence of
inhomogeneity of the bone tissue on the variation of the drilling depth and the
impact of jet time (twj) on the drilling depth were compared to a single water
jet (SWJ) with a similar power. 98 holes were drilled in 14 submerged porcine
tali with two conditions CWJ (impact angle of 30 degrees and 90 degrees ) and
SWJ. The water pressure was 70MPa for all conditions. The water jet diameter was
0.3 mm for CWJ and 0.4 mm for SWJ. twj was set at 1, 3, 5 and 8s. Drilling depth
and hole diameter were measured using microCT scans. A non-parametric Levene's
test was performed to assess a significant difference in variance between
conditions SWJ and CWJ. A regression analysis was used to determine differences
in influence of twj on the drilling depth. Hole diameter differences were
assessed using a one way Anova. A significance level of p<0.05 was set. Condition
CWJ significantly decreases the drilling depth variance caused by the
heterogeneity of the bone when compared to SWJ. The mean depth for CWJ was 0.9 mm
(SD 0.3 mm) versus 4.8 mm (SD 2.0) for SWJ. twj affects the drilling depth less
for condition CWJ (p<0.01, R2=0.30) than for SWJ (p<0.01, R2=0.46). The impact
angle (30 degrees or 90 degrees ) of the CWJ does not influence the drilling
depth nor the variation in depth. The diameters of the resulting holes in the
direction of the jets is significantly larger for CWJ at 90 degrees than for 30
degrees or a single jet. This study shows that CWJ provides accurate depth
control when water jet drilling in an inhomogeneous material such as bone. The
maximum variance measured by using the 95% confidence interval is 0.6 mm opposed
to 5.4 mm for SWJ. This variance is smaller than the accuracy required for bone
debridement treatments (2-4 mm deep) or drilling pilot holes. This confirms that
the use of CWJ is an inherently safe method that can be used to accurately drill
in bones.
PMID- 28501720
TI - Characterization and restoration of degenerated IVD function with an injectable,
in situ gelling alginate hydrogel: An in vitro and ex vivo study.
AB - Intervertebral disc (IVD) degeneration is a naturally, irreparable process that
causes loss in IVD hydration, cellularity, and, mechanical stability. Invasive
surgical attempts to ease back pain and, radiculopathy have shown to cause
increased degeneration along the rest, of the spine. Due to its highly tunable
mechanical and degradation, properties, alginate is a viable option for a less
invasive injectable, repair for IVD degeneration. This study centers on the
characterization, of in situ gelling alginate and subsequent injection into
enzymatically, degraded motion segments., In situ gelation of 2% alginate (% w/v
PBS) was performed using calcium, carbonate (CaCO3) and glucono-delta-lactone
(GDL) and compared to, instantaneously gelled 2% alginate crosslinked with
calcium chloride., After characterization of multiple molar concentrations, a
ratio of, 60mM:120mM CaCO3:GDL was determined to have the most optimum
properties, for injection. Enzymatically degraded bovine caudal motion segments
were, injected with the optimized in situ gelling alginate and mechanically,
loaded; injected motion segments were compared to intact specimens, degraded
specimens, and specimens injected with 20% gelatin to, corroborate with previous
ex vivo injection studies., Overall, injection of in situ curing 2% alginate into
an enzymatically, and mechanically degraded IVD restores function via reduction
of height, loss over long-term cyclic loading, is constrained within the disc
with, no injection site leakage, and successfully fills all void spaces created,
by chemonucleolysis with 1% collagenase-f. These findings, along with the,
ability of alginate to be specifically tailored to support cell, viability, show
promise for a tissue engineered injectable NP substitute for the reversal of disc
degeneration.
PMID- 28501721
TI - Cortical bone elasticity measured by resonant ultrasound spectroscopy is not
altered by defatting and synchrotron X-ray imaging.
AB - In the study of mechanical properties of human bone, specimens may be defatted
before experiments to prevent contamination and the risk of infections. High
energy synchrotron radiation micro-computed tomography (SR-MUCT) is a popular
technique to study bone microstructure. However, little is known about the
effects of defatting or irradiation during SR-MUCT imaging on different elastic
coefficients including shear and longitudinal moduli in different anatomical
directions. In this work, these effects are evaluated on a set of 24 samples
using resonant ultrasound spectroscopy (RUS), which allows one to accurately
measure the complete set of elastic coefficients of cortical bone non
destructively. The results show that defatting with diethylether and methanol and
irradiation up to 2.5kGy has no detectable effect on any of the elastic
coefficients of human cortical bone.
PMID- 28501722
TI - Spatial QRS-T angle in patients with newly diagnosed obstructive sleep apnea
syndrome.
AB - PURPOSE: The aim of the study was to assess the spatial QRS-T angle (QRS-TA) in a
group of newly diagnosed and untreated adult patients with obstructive sleep
apnea syndrome (OSAS) and to identify potential factors affecting this parameter.
PATIENTS AND METHODS: The study group (PSG-confirmed OSAS) included 62
individuals, aged 51.7+/-10.3 years. The control group consisted of 25
individuals, aged 46.6+/-16.6 years with no sleep-disordered breathing. The
diagnosis of OSAS and assessment of its severity was based on unattended all
night screening polysomnography. The spatial QRS-TA was reconstructed from 12
lead ECG using Kors' regression method. RESULTS: Significant differences of
spatial QRS-TA values were found between patients with severe OSAS (36.9+/-18.9
degrees ) and the controls (20.3+/-13.4 degrees ; p<0.01) and between patients
with mild or moderate OSAS (32.3+/-20.1 degrees ) and the controls (p=0.01).
Statistically significant correlations were found between spatial QRS-TA and
polysomnographic indices (i.e. AHI, AI, RDT and RDTI). CONLUSIONS: Spatial QRS-TA
values are significantly higher in patients with OSAS than in controls, thus
indicating increased heterogeneity of myocardial action potential. Further long
term prospective studies evaluating the prognostic value of spatial QRS-TA in
OSAS patients are needed.
PMID- 28501723
TI - Tangeretin alters neuronal apoptosis and ameliorates the severity of seizures in
experimental epilepsy-induced rats by modulating apoptotic protein expressions,
regulating matrix metalloproteinases, and activating the PI3K/Akt cell survival
pathway.
AB - PURPOSE: Epilepsy is complex neural disarray categorized by recurring seizures.
Despite recent advances in pharmacotherapies for epilepsy, its treatment remains
a challenge due to the contrary effects of the drugs. As a result, the
identification of novel anti-epileptic drugs (AEDs) with neuroprotective
properties and few side effects is of great value. Thus, the present study
assessed the treatment effects of tangeretin using a rat model of pilocarpine
induced epilepsy. MATERIALS AND METHODS: Separate groups of male Wistar rats
received oral administrations of tangeretin at 50, 100, or 200mg/kg for 10 days
and then, on the 10th day, they received an intraperitoneal injection of
pilocarpine (30mg/kg). Subsequently, neuronal degeneration and apoptosis were
assessed using Nissl staining and terminal deoxynucleotidyl transferase (TdT)
mediated dUTP nick end labeling (TUNEL) assay procedures. Additionally, the
expressions of phosphatidylinositol-3-kinase (PI3K/Akt) pathway proteins, cleaved
caspase-3, Bad, Bcl-2, Bcl-xL, and Bax were determined using Western blot
analyses. RESULTS: Tangeretin reduced the seizure scores and latency to first
seizure of the rats and effectively activated the pilocarpine-induced suppression
of PI3K/Akt signaling. Additionally, tangeretin effectively regulated the levels
of apoptosis-inducing factor (AIF) in mitochondria as well as the expressions of
apoptotic pathway proteins. Seizure-induced elevations in the activities and
expressions of matrix metalloproteinases (MMPs)-2 and -9 were also modulated.
CONCLUSION: The present results indicate that tangeretin exerted potent
neuroprotective effects against pilocarpine-induced seizures via the activation
of PI3K/Akt signaling and the regulation of MMPs.
PMID- 28501724
TI - Different manifestations of pulmonary embolism in younger compared to older
patients: Clinical presentation, prediction rules and long-term outcomes.
AB - PURPOSE: Data concerning specific manifestations of pulmonary embolism (PE) among
younger patients are scarce. We aimed to evaluate differences in clinical
presentation, PE prediction rules, thrombolytic treatment use and PE outcomes in
younger (<50 years of age) compared to older patients. MATERIAL/METHODS: We
studied 238 consecutive patients with proven PE who were retrospectively
categorized into three PE probability subgroups according to the revised Geneva
score (RGS) and Wells score (WS). Duration of follow-up was up to 115 months.
RESULTS: Younger patients accounted for 19.7% of the study cohort. Obesity and
smoking were significantly more common, while comorbidities were less common
(P<0.05) in the younger patients. According to RGS and WS, younger patients were
more often categorized into the low PE probability subgroup and rarely into the
high probability subgroup (P<0.05). We found no differences in clinical signs,
symptoms, and treatment between the two groups. In-hospital (2% vs. 13%) and long
term (12% vs. 36%) mortality rates were significantly lower in younger patients
(P=0.003). CONCLUSIONS: In younger PE patients, despite differences in
predisposing factors and PE probability grading as assessed by RGS and WS,
clinical features at admission and treatment were similar compared to the older
group. Our findings confirmed lower mortality among younger compared to older
patients.
PMID- 28501725
TI - A device for testing the durability and exploitation reliability of dental
prostheses.
AB - PURPOSE: The aim of this work was to develop the design of the construction of a
stand for testing the operational stability of dental prostheses, designed on the
basis of an own idea. There are no devices that would make it possible to test
complete structures, including the actual kinematics of motion and the influence
of the environment of the oral cavity. MATERIALS AND METHODS: Presented were
several devices used for testing both fixed and removable prostheses. Attention
was paid to their limited possibilities in the area of the tested friction node,
kinematics of motion, and the assessment of the influence of the environment of
the oral cavity on the tested functional quality. The construction was based on
the author's own ideas as well as on a review of the available literature.
RESULTS: As the final result of the research, simplified images of the stand were
presented along with their descriptions. CONCLUSIONS: The experimental
verification of the stand allowed concluding that the research aims have been
achieved. First of all, the device allows testing prosthetic structures of
different sizes and it is possible to load the tested prostheses in randomly
chosen points.
PMID- 28501726
TI - Osteogenic differentiation of mesenchymal stem cells is impaired by bone
morphogenetic protein 7.
AB - PURPOSE: Mesenchymal stem cells (MSCs) are multipotent adult stem cells and
present in practically all tissues but originally identified within the bone
marrow (BM). The differentiation potential of these cells is generally impaired
when culturing in vitro for cell expansion. The aim of this study is to speedily
increase the numbers of bone marrow derived mesenchymal stem cells (BM-MSCs) with
substantially maintaining their differentiation potential in vitro and improving
bone formation in vivo. MATERIALS AND METHODS: BM-MSCs isolated from rats were
sequentially cultured in alpha-MEM containing basic fibroblast growth factor
(FGF2) and/or insulin to stimulate proliferation and osteogenic commitment, and
in the medium with the addition of bone morphogenetic protein 2 (BMP2) and/or
bone morphogenetic protein 7 (BMP7) to arouse differentiation. The expression of
genes markedly associating the commitment and differentiation were investigated
in vitro using real-time PCR technique and mineralization assay, while the
capacity of inducing bone formation by the established conditions was determined
in vivo using a rat model. RESULTS: The BM-MSCs greatly proliferated with active
transcription of runx2 and osterix genes when induced by FGF2 and insulin. The in
vitro mineralization was enhanced by BMP2, but the extent was diminished when
BMP2 was replaced or supplemented by BMP7. Formation of new small blood vessels
was notably detected when the cells were respectively challenged by FGF2 plus
insulin and BMP2. CONCLUSION: These data are valuable in choosing growth factors
for proper bone repair. However, optimization of the established system would be
essential when the cells of human source are applied.
PMID- 28501727
TI - Methods to evaluate arterial structure and function in children - State-of-the
art knowledge.
AB - BACKGROUND: With increasing rates of hypertension, obesity, and diabetes in the
pediatric population, wide available, and reproducible methods are necessary to
evaluate arterial structure and function in children and adolescents. METHODS:
MEDLINE/Pubmed was searched for articles published in years 2012-2017 on
methodology of, current knowledge on, and limitations of the most commonly used
methods to evaluate central, proximal and coronary arteries, as well as
endothelial function in pediatric patients. RESULTS: Among 1528 records screened
(including 1475 records from years 2012 to 2017) 139 papers were found suitable
for the review. Following methods were discussed in this review article:
ultrasound measurements of the intima-media thickness, coronary calcium scoring
using computed tomography, arterial stiffness measurements (pulse wave velocity
and pulse wave analysis, carotid artery distensibility, pulse pressure, and
ambulatory arterial stiffness index), ankle-brachial index, and methods to
evaluate vascular endothelial function (flow-mediated vasodilation, peripheral
arterial tonometry, Doppler laser flowmetry, and cellular and soluble markers of
endothelial dysfunction). CONCLUSIONS: Ultrasonographic measurement of carotid
intima-media thickness and measurement of pulse wave velocity (by oscillometry or
applanation tonometry) are highly reproducible methods applicable for both
research and clinical practice with proved applicability for children aged >=6
years or with height >=120cm. Evaluation of ambulatory arterial stiffness index
by ambulatory blood pressure monitoring is another promising option in pediatric
high-risk patients. Clearly, further studies are necessary to evaluate usefulness
of these and other methods for the detection of subclinical arterial damage in
children.
PMID- 28501728
TI - Effects of fine air particulates on gene expression in non-small-cell lung
cancer.
AB - PURPOSE: Airborne particulate matter smaller than 2.5MUm (PM2.5) has been shown
to induce adverse health effects through various mechanisms. However, its effects
on gene expression in non-small-cell lung cancer (NSCLC) remain undefined. The
aim of this study was to analyze the expression profile of PM2.5-induced adverse
health effects on human. MATERIALS AND METHODS: We performed RNA sequencing to
elucidate key molecular effects of PM2.5 collected from Shenyang China, to
identify potential diagnostic markers or therapeutic targets, and further
validated these differences in gene expression by using quantitative PCR in A549
and H1299 human non-small-cell lung cancer cell lines. To investigate the
functional changes on PM2.5 exposed cells, we carried out the viability assay for
the cell counting, and the Boyden chamber assay for invasion. RESULTS: We found
143 genes that were expressed at least twice as much, or no more than half as
much, in NSCLC cells exposed to PM2.5 than in unexposed cells. Results showed
deregulated genes confronted PM2.5 exposure were significantly expressed, but
commonly expressed in NSCLC cells. In addition, according to the viability assay
and the Boyden chamber assay, PM2.5 exposed cells which have more competent on
proliferation and invasion can keep the line with the results in RNA-Seq.
CONCLUSION: Our data may provide a more specific understanding of the signaling
patterns associated with pathogenesis, and lead to novel markers and therapeutic
targets for NSCLC.
PMID- 28501729
TI - Mulberry leaf extract decreases digestion and absorption of starch in healthy
subjects-A randomized, placebo-controlled, crossover study.
AB - PURPOSE: Mulberry (Morus alba L.) leaf tea has recently received much attention
as a dietary supplement due to the wide range of putative health benefits, such
as antidiabetic effects. Nevertheless, data evaluating its influence on
carbohydrate metabolism in humans are scarce. The present study aims to
investigate the effect of mulberry leaf extract supplementation on starch
digestion and absorption in humans. MATERIALS AND METHODS: The study comprised of
25 healthy subjects, aged 19-27 years. In all subjects, a starch 13C breath test
was performed twice in a crossover and single blind design. Subjects were
initially randomized to ingest naturally 13C-abundant cornflakes (50g
cornflakes+100ml low fat milk) either with the mulberry leaf extract (36mg of
active component-1-deoxynojirimycin) or the placebo and each subject received the
opposite preparation one week later. RESULTS: The cumulative percentage dose
recovery was lower for the mulberry leaf extract test than for the placebo test
(median [quartile distribution]: 13.9% [9.9-17.4] vs. 17.2% [13.3-20.6];
p=0.015). A significant decrease was detectable from minute 120 after the
ingestion. CONCLUSIONS: A single dose of mulberry leaf extract taken with a test
meal decreases starch digestion and absorption. These findings could possibly be
translated into everyday practice for improvement of postprandial glycemic
control.
PMID- 28501730
TI - Larvicidal activity of vegetable oils and esterified compounds against Culex
quinquefasciatus (Diptera: Culicidae).
AB - Control of Culex quinquefasciatus using chemical insecticides may result in the
selection of resistant mosquito strains. Thus, the use of plant-derived products
has been studied as alternative for the mosquito control. Fatty acid methyl
esters (FAMEs) obtained by transesterification of vegetable oils may result in
compounds with larvicidal potential against C. quinquefasciatus. However, little
is known about the morphological, physiological or biochemical effects that these
FAMEs may have on mosquito larvae. The present study reports the effects of these
FAMEs in mosquito larvae. The FAMEs were obtained by transesterification of
canola, corn, sunflower, and soybean oils with acid catalysis and the
determination of FAMEs composition was done by gas chromatography-mass
spectrometry (GC-MS). Larvae of C. quinquefasciatus were exposed to different
concentrations of the vegetable oils and FAMEs. Thereby, different FAMEs showed
LC50 values ranging from 42.32 to 196.27mg/L against C. quinquefasciatus larvae.
The methyl ester obtained from sunflower oil showed the lowest LC50. Histology of
C. quinquefasciatus larvae exposed to LC50 of FAMEs was performed and changes in
the midgut and fat body morphology were identified. Therefore, larval mortality
and changes in the internal organs suggested that FAMEs might be a promising new
class of larvicidalcompounds. Cytotoxicity of FAMEs compounds was assessed with
the HeLa human cell line and no effect was observed.
PMID- 28501731
TI - Learning and unlearning dignity in care: Experiential and experimental
educational approaches.
AB - Guarding against loss of human dignity is fundamental to nursing practice. It is
assumed in the existing literature that 'dignity' as a concept and 'dignity in
care' as a practice is amenable to education. Building on this assumption, a
range of experiential and experimental educational approaches have been used to
enhance students' understanding of dignity. However, little is known about
student nurses' views on whether dignity is amenable to education and, if so,
which educational approaches would be welcomed. This mixed-methods study used an
online questionnaire survey and focus groups to address these questions. Student
nurses in Scotland completed online questionnaires (n = 111) and participated in
focus groups (n = 35). Students concluded that education has transformative
potential to encourage learning around the concept of dignity and practice of
dignity in care but also believed that dignity could be unlearned through
repeated negative practice exposures. Experiential and experimental educational
approaches were welcomed by student nurses, including patient testimony, role
play, simulation, and empathy exercises to step into the lives of others. Nurse
educators should further integrate experiential and experimental educational
approaches into undergraduate and postgraduate nursing curricula to guard against
the loss of learning around dignity students believed occurred over time.
PMID- 28501732
TI - Asymmetrical stabilization and mobilization exploited during static single leg
stance and goal directed kicking.
AB - The motor control properties of the right and left legs are dependent on the
stabilization and mobilization features of the motor tasks. The current
investigation examined the right and left leg control differences - interlateral
asymmetries - during static single leg stance and dynamic goal directed kicking
with an emphasis of the asymmetrical stabilization and mobilization components of
movements. Ten young, healthy, right-leg preferred individuals with minimal
kicking experience completed both tests on each limb. During static single leg
stance, participants were requested to stand as still as possible with one leg in
contact with a force platform. Interlateral asymmetries of the standing leg were
quantified using postural variability measures of the center of pressure (COP)
standard deviation in the anterior-posterior (SD-COPAP) and medial-lateral (SD
COPML) directions, resultant COP length and velocity, and 95% COP elliptical
area. During dynamic goal directed kicking, participants stood on two adjacent
force platforms in a side-by-side foot position and kicked a soccer ball toward
three different directions as soon as they received an auditory cue of kicking.
Three targets were located -30 degrees , 0 degrees or 30 degrees in front and
3.05 m away from the participants' midline. Participants kicked the ball toward
the targets with each of their feet. The vertical ground reaction force (vGRF) of
the kicking leg was used to define the preparation (from above two standard
deviations of vGRF baseline to toe-off) and swing (from toe-off to toe-return)
phases of dynamic kicking. To determine the presence of interlateral asymmetries
during dynamic kicking, the magnitude and timing of the anticipatory postural
adjustments (APA) during the preparation phase of kicking were quantified using
the lateral net COP (COPnet-ML) time series derived from both force platforms.
Postural variability measures of the support leg and the kinematic joint range of
motion (JROM) trajectories of the kicking leg were also used to examined
interlateral asymmetries. During static stance, no between-leg significance was
identified for all dependent measures of COP variability suggesting symmetrical
stabilization. During the preparation phase of kicking, both right and left leg
kicking exhibited a similar level of APA magnitude, although the left leg kicking
was shown to reach its maximum APA magnitude earlier than the right leg. In the
support leg role, the right leg showed greater COP variability in the ML
direction as compared to the left support leg and greater COP variability was
observed when kicking in the ipsilateral direction compared to the center and
contralateral directions. For mobilization control, the left kicking leg showed
greater JROM displacements at the distal (knee and ankle) joints and reduced JROM
primarily with hip frontal plane movements compared to the right kicking leg. The
reported interlateral asymmetries during kicking may reflect a behavioral
adaptation that results in differential stabilization between the right and left
legs. Overall, the findings suggest that novel tasks, such as dynamic goal
directed kicking, appear to be more sensitive than static balance in identifying
interlateral asymmetries.
PMID- 28501733
TI - Insomnia in adult attention-deficit/hyperactivity disorder: A comparison with
borderline personality disorder population in a clinical setting and control
participants.
AB - OBJECTIVES: Many adults with attention-deficit/hyperactivity disorder (ADHD)
report sleeping difficulties. The relationship between sleep and ADHD is poorly
understood, and shows discrepancies between subjective and objective measures. In
order to determine the specificity of sleep-associated symptoms in ADHD,
subjective sleep assessments among ADHD adult patients were compared with control
subjects and with individuals suffering from borderline personality disorder
(BPD). METHODS: 129 outpatients with ADHD, 70 with BPD (including 17 patients
with BPD and ADHD comorbidity), and 65 control participants were assessed for
sleep quality, insomnia, and sleepiness, using the Pittsburgh Sleep Quality Index
(PSQI), the Insomnia Severity Index (ISI), and the Epworth Sleepiness Scale
(ESS). RESULTS: ADHD- and BPD-sufferers achieved higher insomnia and lower sleep
quality scores than control subjects. Clinical groups did not differ in terms of
sleep quality, although insomnia was more severe among BPD patients. Depression
scores explained most of sleep symptoms, but even when controlling for
depression, ADHD sufferers showed higher sleep latency. Inattentive symptoms were
associated with somnolence, while hyperactive/impulsive symptoms were associated
with insomnia and lower sleep efficiency. CONCLUSION: Sleep-related symptoms
associated with ADHD were partly explained by non-specific factors, especially
depression symptoms. In a dimensional perspective, hyperactive and inattentive
symptoms were associated with specific sleep symptoms.
PMID- 28501734
TI - Social factors affect motor and anxiety behaviors in the animal model of
attention-deficit hyperactivity disorders: A housing-style factor.
AB - The present study examines whether housing style (e.g., single housing, same
strain-grouped housing, and different-strain-grouped housing) and rat strain
(e.g., spontaneous hypertension rats [SHR] and Wistar-Kyoto rats [WKY]) mediate
motor function and anxiety behavior in the open field task. From week 4 through
week 10 following birth, the rats were measured 30min for locomotor activity and
anxiety once per week in the open field task. The SHR rats exhibited
hyperactivity in total distance traveled and movement time to form the animal
model of ADHD. The SHR rats spent more time inside the square and crossed the
inside-outside line more often than the WKY rats, indicating the SHR rats
exhibited less anxiety behavior. The different-strain-grouped housing style (but
neither the same-strain-grouped housing style nor the single housing style)
decreased total distance traveled and facilitated anxiety behavior. The motor
function was negatively correlated with anxiety behavior for SHR rats but not for
WKY rats. Housing styles had a negative correlation between motor function and
anxiety behavior. The present findings provide some insights regarding how social
factors (such as housing style) affect motor function and anxiety behavior
related to ADHD in a clinical setting.
PMID- 28501735
TI - Dose- and time-dependent effects of mirtazapine on the expression of cocaine
induced behavioral sensitization in rats.
AB - Relapse to cocaine use is a major problem in the clinical treatment of cocaine
dependence. Antidepressant medications have been studied as potential therapeutic
drugs to relieve a cocaine dependence disorder. Mirtazapine is an antidepressant
implicated in reducing behavioral alterations induced by drugs of abuse. We have
reported elsewhere that 30mg/kg mirtazapine administered for 30 days during
cocaine extinction significantly attenuated the induction and expression of
cocaine-induced locomotor sensitization and decreased the duration of the cocaine
induced locomotor effect. This study focused on exploring whether different
mirtazapine dosing regimens could optimize and/or improve the effect of 30mg/kg
mirtazapine administered for 30 days on cocaine-induced locomotor activity during
the expression phase of behavioral sensitization. Our study revealed that the
daily dosing regimen with a fixed dose of mirtazapine (30mg/kg ip) over 60 days
improved the decrease in cocaine-induced locomotor activity and behavioral
sensitization obtained by dosing of 30mg mirtazapine for 30 days. In addition, it
showed that a dosing regimen of 30mg/Kg mirtazapine for 30 days managed to reduce
cocaine toxicity. These results suggested that dosage of mirtazapine for 30
consecutive days may be an effective therapy.
PMID- 28501736
TI - Role of IL-8, CRP and epidermal growth factor in depression and anxiety patients
treated with mindfulness-based therapy or cognitive behavioral therapy in primary
health care.
AB - Epidermal growth factor (EGF) and inflammatory markers have been associated with
various neuro-psychiatric disorders. However, their role in mild to moderate
depression and anxiety patients treated with mindfulness-based group therapy
(mindfulness) or cognitive behavioral therapy (CBT) is not known. In this study
we analyzed plasma levels of interleukin (IL)-6, IL-8, high sensitivity C
reactive protein (hsCRP) and EGF before (baseline) and after treatment (8 weeks)
and investigated their role in response to both arms of the treatment. To cover
variety of mental symptoms, treatment response was analyzed by four scales, the
Montgomery-Asberg depression rating scale (MADRS), Hospital anxiety and
depression scale- Depression (HADS-D) and anxiety (HADS-A) and patients health
questionnaire-9. EGF levels were significantly decreased after both mindfulness
and CBT and were associated with treatment response on all scales independent of
the use of tranquilizers and antidepressant treatment. Moreover, baseline EGF
levels were significantly associated only with baseline scores of anxiety scale.
Levels of inflammatory markers analyzed in this study, were not significantly
associated with treatment response on any scale. Our findings suggest that
improvement in symptoms of depression and anxiety after both mindfulness and CBT
is associated with changes in EGF levels but not with the inflammatory markers.
PMID- 28501738
TI - Performance and psychometric properties of the Interpersonal Support Evaluation
List (ISEL) in older adults with Complicated Grief.
AB - BACKGROUND: Complicated Grief (CG) is a recently recognized bereavement-related
mental health disorder. Social support is commonly measured with the
Interpersonal Support Evaluation List (ISEL), a 40-item, 4-factor, self-report
measure. Though the ISEL has been well-studied, no identified research has
examined its psychometric properties or performance in older adults with CG.
METHODS: We examined the psychometric properties of the ISEL in adults age >=60
who enrolled in a psychotherapy treatment study for CG in New York City. We also
examined the association of ISEL scores with CG severity, and with clinical and
sociodemographic variables. RESULTS: Internal consistency of the ISEL was high
(alpha=0.95). Confirmatory factor analysis indicated that most of the ISEL items
loaded strongly (>0.45) on the original 4 factors. Mean ISEL score was 68.1,
which indicated lower social support than population norms. ISEL scores were
significantly but modestly negatively correlated with grief severity. ISEL total
scores also varied by sociodemographic and clinical variables; never being
married, depression or anxiety diagnosis, and living alone were all associated
with lower ISEL scores. LIMITATIONS: A clinical help-seeking sample, with low
sociodemographic and geographic variability, may limit the generalizability of
the findings. Also, analyses were cross-sectional and directionality of
associations could not be determined. CONCLUSIONS: The 40-item ISEL may be a
useful measure for those studying social support in the context of CG. Given the
strikingly low levels of social support, intervention strategies for CG should
include components addressing social support.
PMID- 28501737
TI - The BCR/ABL tyrosine kinase inhibitor, nilotinib, stimulates expression of IL
1beta in vascular endothelium in association with downregulation of miR-3p.
AB - BCR/ABL tyrosine kinase inhibitors (TKIs) have significantly improved the
prognosis for in dividuals with chronic myeloid leukemia (CML). However, many
patients treated with TKIs suffer from TKI-related complications. In particular,
vascular events such as peripheral artery occlusive disease have become aserious
clinical problem for patients who receive the TKI, nilotinib. At present, the
molecular mechanisms by which TKIs cause vascular endothelial cell insults remain
unknown.This study explored the effects of the TKIs, imatinib, nilotinib and
dasatinib, on vascular endothelial cells in vitro, and found that only nilotinib
induced expression of interleukin-1beta (IL-1beta) by vascular endothelial cells.
Nilotinib-induced IL-1beta expression stimulated the adhesion of monocytes to
vascular endothelial cells in association with an increase in levels of adhesion
molecules. MicroRNA database searching identified miR-3121-3p binding sites in
the 3'-UTR of the IL-1beta gene. Exposure of endothelial cells to nilotinib
caused downregulation of miR-3121-3p in these cells. Importantly, forced
expression of miR-3121-3p counteracted nilotinib-induced expression of IL-1beta.
Importantly, serum levels if IL-1beta were significantly elevated in CML patients
receiving nilotinib (n=14) compared to those receiving other TKIs (n=16) (3.76+/
1.22pg/ml vs 0.27+/-0.77pg/ml, p<0.05). Taken together, our data suggest that
nilotinib decreases levels of miR-3121-3p resulting in an increase in expression
of IL-1beta and adhesion molecules in vascular endothelial cells. The miR-3121
3p/IL-1beta axis could be a potential target to prevent vascular events in CML
patients with high risk of vascular events.
PMID- 28501740
TI - Prefrontal and amygdala engagement during emotional reactivity and regulation in
generalized anxiety disorder.
AB - BACKGROUND: Emotion dysregulation is prominent in generalized anxiety disorder
(GAD), characterized clinically by exaggerated reactivity to negative stimuli and
difficulty in down-regulating this response. Although limited research implicates
frontolimbic disturbances in GAD, whether neural aberrations occur during
emotional reactivity, regulation, or both is not well understood. METHODS: During
functional magnetic resonance imaging (fMRI), 30 individuals with GAD and 30
healthy controls (HC) completed a well-validated explicit emotion regulation task
designed to measure emotional reactivity and regulation of reactivity. During the
task, participants viewed negative images ('Look-Negative' condition) and, on
some trials, used a cognitive strategy to reduce negative affective response
('Reappraise' condition). RESULTS: Results from an Analysis of Variance corrected
for whole brain multiple comparisons showed a significant group x condition
interaction in the left amygdala and left inferior frontal gyrus (IFG). Results
from post-hoc analyses showed that the GAD group engaged these regions to a
greater extent than HCs during Look-Negative but not Reappraise. Behaviorally,
the GAD group reported feeling more negative than the HC group in each condition,
although both groups reported reduced negative affect following regulation.
LIMITATIONS: As comorbidity was permitted, the presence of concurrent disorders,
like other anxiety disorders and depression, detracts our ability to classify
neural engagement particular to GAD alone. CONCLUSIONS: Individuals with GAD
exhibited over-engagement of amygdala and frontal regions during the viewing of
negative images, compared to HCs. Together, these aberrations may indicate that
deficits in emotional reactivity rather than regulation contribute to emotion
dysregulation in those with GAD.
PMID- 28501739
TI - Risk of postpartum episodes in women with bipolar disorder after lamotrigine or
lithium use during pregnancy: A population-based cohort study.
AB - BACKGROUND: Women with bipolar disorder are at high risk for relapse/recurrence
postpartum. Among all mood stabilizers, lithium has the largest evidence base for
efficacy in the peripartum period, but lamotrigine is increasingly prescribed for
bipolar spectrum disorders during pregnancy. The aim of this study was to
investigate whether lamotrigine use during pregnancy is as effective as lithium
in the prevention of severe episodes postpartum. METHODS: Danish national
registries were used to identify pregnancies of women with a diagnosis of bipolar
spectrum disorders at the time of conception who used lamotrigine or lithium
during pregnancy. We compared the risk of inpatient psychiatric admission within
three months postpartum between women who used lamotrigine (N=55) versus lithium
(N=59) during pregnancy. A logistic regression model was used to calculate crude
and adjusted odds ratios. RESULTS: We did not find a significant difference in
the risk of postpartum psychiatric admission between women who used lamotrigine
versus lithium during pregnancy (7.3% versus 15.3% respectively, adjusted OR
0.83; 95% CI 0.22-3.14). We adjusted for year of delivery, parity, previous
admissions and antidepressant/benzodiazepine use during pregnancy. Other
variables did not differ substantially between groups. LIMITATIONS: We used an
observational design and therefore patients were not randomized to lamotrigine or
lithium. The study has a small sample size. CONCLUSIONS: Lamotrigine was not
inferior to lithium in the prevention of severe postpartum episodes. Our findings
suggest lamotrigine could be a reasonable alternative treatment option for
bipolar disorder during pregnancy in patients with vulnerability for depression
and may prevent severe episodes postpartum.
PMID- 28501741
TI - Executive functioning deficits among adults with Bipolar Disorder (types I and
II): A systematic review and meta-analysis.
AB - BACKGROUND: Executive functioning (EF) deficits contribute to a significant
proportion of the burden of disease associated with bipolar disorder (BD). Yet,
there is still debate in the literature regarding the exact profile of executive
functioning in BD. The purpose of the present project was to assess whether EF
deficits exist among adults suffering BD, and whether these deficits (if
apparent) differ by BD subtype. METHODS: A systematic search identified relevant
literature. Randomised controlled trials that used neuropsychological assessment
to investigate EF among adults 16-65 years) with a remitted DSM diagnosis of BD
(type I or II) were included. Studies were published between 1994 and 2015. A
systematic review and meta-analysis were undertaken. For individual studies,
standardised mean differences (Cohen's d) and 95% confidence intervals were
calculated and represented in forest plots to illustrate differences in executive
performance between groups. Summary effects were produced and tests of
heterogeneity employed to assess the dispersion and generalisability of results.
RESULTS: Thirty-six studies met criteria for inclusion. Six domains of EF were
identified: Set-shifting (SS), inhibition (INH), planning (PLA), verbal fluency
(VF), working memory (WM), and attention (ATT). BD1s performed worse than HCs in
all domains. BD2s demonstrated impairment in VF, WM, SS, and ATT. The results
were mixed for comparisons between BD1s and BD2s, but revealed that BD2s can
experience similar (or sometimes greater) EF impairment. LIMITATIONS: Only a
limited number of studies that included BD2 samples were available for inclusion
in the current study. Subgroup analysis to elucidate potential moderators of
within-study variance was not undertaken. CONCLUSION: This is the first
systematic review and meta-analysis to have compared the EF of remitted BD1s,
BD2s, and HCs. The results provided useful insight into the EF profile of
patients with BD, and offered commentary as to some of the contradictory results
reported in the literature. A standardised methodological protocol for assessment
of EF in BD was proposed. The information in this review could enhance our
understanding of EF impairment inherent in BD, and the methods and efficacy with
which clinicians assess and treat this population.
PMID- 28501742
TI - Differences in the imaging features and distribution of non-indolent and indolent
mastocytosis: a single institution experience of 29 patients.
AB - PURPOSE: Compare imaging features of indolent and non-indolent mastocytosis.
METHODS: For 29 patients, imaging features, imaging indications, and distribution
of indolent and non-indolent mastocytosis subtypes were analyzed. RESULTS: 16/29
(55%) patients had three distinct patterns of osseous abnormality, not
significantly differing between cohorts. Non-indolent disease was more likely to
present with hepatomegaly (p=0.0004), splenomegaly (p=0.0097), and
lymphadenopathy (p=0.0079). CT, was the most common initial imaging modality,
ordered to stage disease in 20 of 29 patients (69%). CONCLUSION: Understanding
patterns of involvement of indolent and nonindolent mastocytosis across
modalities could assist radiologists in evaluating mastocytosis.
PMID- 28501743
TI - Antarctic fish versus human cytoglobins - The same but yet so different.
AB - The cytoglobins of the Antarctic fish Chaenocephalus aceratus and Dissostichus
mawsoni have many features in common with human cytoglobin. These cytoglobins are
heme proteins in which the ferric and ferrous forms have a characteristic
hexacoordination of the heme iron, i.e. axial ligation of two endogenous
histidine residues, as confirmed by electron paramagnetic resonance, resonance
Raman and optical absorption spectroscopy. The combined spectroscopic analysis
revealed only small variations in the heme-pocket structure, in line with the
small variations observed for the redox potential. Nevertheless, some striking
differences were also discovered. Resonance Raman spectroscopy showed that the
stabilization of an exogenous heme ligand, such as CO, occurs differently in
human cytoglobin in comparison with Antarctic fish cytoglobins. Furthermore,
while it has been extensively reported that human cytoglobin is essentially
monomeric and can form an intramolecular disulfide bridge that can influence the
ligand binding kinetics, 3D modeling of the Antarctic fish cytoglobins indicates
that the cysteine residues are too far apart to form such an intramolecular
bridge. Moreover, gel filtration and mass spectrometry reveal the occurrence of
non-covalent multimers (up to pentamers) in the Antarctic fish cytoglobins that
are formed at low concentrations. Stabilization of these oligomers by disulfide
bridge formation is possible, but not essential. If intermolecular disulfide
bridges are formed, they influence the heme-pocket structure, as is shown by EPR
measurements.
PMID- 28501744
TI - Strategy for improved NH2 detection in combustion environments using an
Alexandrite laser.
AB - A new scheme for NH2 detection by means of laser-induced fluorescence (LIF) with
excitation around wavelength 385nm, accessible using the second harmonic of a
solid-state Alexandrite laser, is presented. Detection of NH2 was confirmed by
identification of corresponding lines in fluorescence excitation spectra measured
in premixed NH3-air flames and on NH2 radicals generated through NH3 photolysis
in a nonreactive flow at ambient conditions. Moreover, spectral simulations allow
for tentative NH2 line identification. Dispersed fluorescence emission spectra
measured in flames and photolysis experiments showed lines attributed to
vibrational bands of the NH2 A2A1<-X2B1 transition but also a continuous
structure, which in flame was observed to be dependent on nitrogen added to the
fuel, apparently also generated by NH2. A general conclusion was that
fluorescence interferences need to be carefully considered for NH2 diagnostics in
this spectral region. Excitation for laser irradiances up to 0.2GW/cm2 did not
result in NH2 fluorescence saturation and allowed for efficient utilization of
the available laser power without indication of laser-induced photochemistry.
Compared with a previously employed excitation/detection scheme for NH2 at around
630nm, excitation at 385.7nm showed a factor of ~15 higher NH2 signal. The
improved signal allowed for single-shot NH2 LIF imaging on centimeter scale in
flame with signal-to-noise ratio of 3 for concentrations around 1000ppm,
suggesting a detection limit around 700ppm. Thus, the presented approach for NH2
detection provides enhanced possibilities for characterization of fuel-nitrogen
combustion chemistry.
PMID- 28501745
TI - Paper based diagnostics for personalized health care: Emerging technologies and
commercial aspects.
AB - Personalized health care (PHC) is being appreciated globally to combat clinical
complexities underlying various metabolic or infectious disorders including
diabetes, cardiovascular, communicable diseases etc. Effective diagnoses majorly
depend on initial identification of the causes which are nowadays being practiced
in disease-oriented approach, where personal health profile is often overlooked.
The adoption of PHC has shown significantly improved diagnoses in various
conditions including emergency, ambulatory, and remote area. PHC includes
personalized health monitoring (PHM), which is its integral part and may provide
valuable information's on various clinical conditions. In PHC, bio-fluids are
analyzed using various diagnostic devices including lab based equipment and
biosensors. Among all types of biosensing systems, paper based biosensors are
commercially attracted due to its portability, easy availability, cheaper
manufacturing cost, and transportability. Not only these, various intrinsic
properties of paper has facilitated the development of paper based miniaturized
sensors, which has recently gained ASSURED (Affordable, Sensitive, Specific, User
friendly, Rapid and Robust, Equipment free, Deliverable to all end-users) status
for point of care diagnosis in miniaturized settings. In this review, importance
of paper based biosensors and their compatibility for affordable and low cost
diagnostics has been elaborated with various examples. Limitations and strategies
to overcome the challenges of paper biosensor have also been discussed. We have
provided elaborated tables which describe the types, model specifications,
sensing mechanisms, target biomarkers, and analytical performance of the paper
biosensors with their respective applications in real sample matrices. Different
commercial aspects of paper biosensor have also been explained using SWOT
(Strength, Weakness, Opportunities, Threats) analysis.
PMID- 28501746
TI - A label-free nanostructured plasmonic biosensor based on Blu-ray discs with
integrated microfluidics for sensitive biodetection.
AB - Nanostructure-based plasmonic biosensors have quickly positioned themselves as
interesting candidates for the design of portable optical biosensor platforms
considering the potential benefits they can offer in integration,
miniaturization, multiplexing, and real-time label-free detection. We have
developed a simple integrated nanoplasmonic sensor taking advantage of the
periodic nanostructured array of commercial Blu-ray discs. Sensors with two gold
film thicknesses (50 and 100nm) were fabricated and optically characterized by
varying the oblique-angle of the incident light in optical reflectance
measurements. Contrary to the use normal light incidence previously reported with
other optical discs, we observed an enhancement in sensitivity and a narrowing of
the resonant linewidths as the light incidence angle was increased, which could
be related to the generation of Fano resonant modes. The new sensors achieve a
figure of merit (FOM) up to 35 RIU-1 and a competitive bulk limit of detection
(LOD) of 6.3*10-6 RIU. These values significantly improve previously reported
results obtained with normal light incidence reflectance measurements using
similar structures. The sensor has been combined with versatile, simple, ease to
fabricate microfluidics. The integrated chip is only 1cm2 (including a PDMS flow
cell with a 50um height microfluidic channel fabricated with double-sided
adhesive tape) and all the optical components are mounted on a 10cm*10cm portable
prototype, illustrating its facile miniaturization, integration and potential
portability. Finally, to assess the label-free biosensing capability of the new
sensor, we have evaluated the presence of specific antibodies against the GTF2b
protein, a tumor-associate antigen (TAA) related to colorectal cancer. We have
achieved a LOD in the pM order and have assessed the feasibility of directly
measuring biological samples such as human serum.
PMID- 28501747
TI - Equilibrium, kinetic and thermodynamic studies for adsorption of BTEX onto
Ordered Mesoporous Carbon (OMC).
AB - Chemical and petrochemical industries produce substantial amounts of wastewater
everyday. This wastewater contains organic pollutants such as benzene, toluene,
ethylbenzene and xylenes (BTEX) that are toxic to human and aquatic life. Ordered
Mesoporous Carbon (OMC), the adsorbent that possesses the characteristics of an
ideal adsorbent was investigated to understand its properties and suitability for
BTEX removal. Adsorption isotherms, adsorption kinetics, the effects of initial
BTEX concentrations and temperatures on the adsorption process were studied. The
OMCs were characterized using surface area and pore size analyzer, transmission
electron microscopy (TEM), elemental analysis, thermogravimetric analysis (TGA)
and fourier transform infrared spectroscopy (FTIR). The results suggested that
the Langmuir Isotherm and Pseudo-Second-Order Models described the experimental
data well. The thermodynamic parameters, Gibbs free energy (DeltaG degrees ), the
enthalpy change (DeltaH degrees ) and the entropy change (DeltaS degrees ) of
adsorption indicated that the adsorption processes were physical, endothermic,
and spontaneous. In addition, OMC had 27% higher overall adsorption capacities
compared to granular activated carbon (GAC).
PMID- 28501748
TI - Systematic screening and characterization of prototype constituents and
metabolites of total astragalosides using HPLC-ESI-IT-TOF-MSn after oral
administration to rats.
AB - Astragalosides (AGs) are the main bioactive constituents in Astragali Radix (AR),
and have a wide range of pharmacological properties, including immunoregulatory,
cardioprotective, neuroprotective, antioxidative, antidiabetic, and
antinociceptive effects. However, the metabolism of total AGs remains unclear. To
clarify the metabolic fate of AGs after oral administration to rats, total AGs
were isolated from AR extracts using AB-8 macroporous resin chromatography and
preparative HPLC, and then analyzed using HPLC-DAD-ELSD and LC-MS. HPLC-ESI-IT
TOF-MSn was used to systematically screen and characterize prototype constituents
and metabolites of total AGs in rat feces, urine, and plasma samples. As a
result, 123 AG-related compounds from feces were detected and structurally
characterized. Among the 123 compounds, 107 were phase I metabolites, of which 91
were new metabolites, and 73 were new compounds. In addition, six prototype
constituents in urine, and one in plasma were detected. The main metabolic sites
in the structure of cycloastragenol (CAG), the aglycone of AGs, were found to be
the 9, 19-cyclopropane ring (E ring) and the 20, 24-furan ring (F ring). The
cleavage mode of CAG derivatives in negative ion mode was identified, and was
found to be highly dependent on the integrity of the E ring. Mono- to tetra
hydroxylated and carboxyl substituted metabolites were tentatively identified.
Deglycosylation, hydroxylation, dehydrogenation, isomerization, ring cleavage,
and carboxyl substitution were considered to be the major metabolic reactions
involved in the formation of the metabolites, among which carboxyl substitution
was a novel metabolic reaction. In summary, after total AGs were orally
administered to rats, their constituents were extensively metabolized in a phase
I manner, and the metabolites were excreted mainly into feces. To our knowledge,
this is the first systematic study on the metabolism of total AGs. The results
give us insight into the metabolic profiles of total AGs in vivo, and provide a
foundation for identifying effective forms of AGs and exploring their mechanism
in future studies.
PMID- 28501749
TI - Characterization of flavonol mono-, di-, tri- and tetra-O-glycosides by ultra
performance liquid chromatography-electrospray ionization-quadrupole time-of
flight mass spectrometry and its application for identification of flavonol
glycosides in Viola tianschanica.
AB - In this study, 21 flavonol O-glycoside standards including flavonol mono-, di-,
tri- and tetra-O-glycosides have been systematically studied by ultra-high
performance liquid chromatography-electrospray ionization-quadrupole time-of
flight mass spectrometry (UPLC-ESI-QTOF-MS/MS) in the negative ionization mode to
analyze their fragmentation patterns. Here for the first time, the Z23- fragment
(corresponding to the loss of C-2" terminal sugar moiety) was observed in MS/MS
spectra of flavonol 3-O-triglycosides. The intensity ratio of [Y0-H]-/Y0- was
proposed as a criterion to distinguish the interglycosidic 1->2 and 1->6 linkages
in flavonol 3-O-diglycosyl-7-O-monoglycosides. The established fragmentation
behaviors have been successfully applied to characterization of flavonol
glycosides in Viola tianschanica. A total of 30 flavonoid glycosides including 3
flavonol mono-O-glycosides, 10 di-O-glycosides, 10 tri-O-glycosides, 4 tetra-O
glycosides and 3 flavone di-C-glycosides were identified or tentatively
identified on the base of their UV profiles, MS/MS data and/or by comparing with
reference substances. Among these 15 flavonoid glycosides were reported from V.
tianschanica for the first time.
PMID- 28501750
TI - Development, validation and application of a novel liquid chromatography tandem
mass spectrometry assay measuring uracil, 5,6-dihydrouracil, 5-fluorouracil, 5,6
dihydro-5-fluorouracil, alpha-fluoro-beta-ureidopropionic acid and alpha-fluoro
beta-alanine in human plasma.
AB - The plasma 5,6-dihydrouracil/uracil (UH2/U) ratio is a possible phenotypic marker
of dihydropyrimidine dehydrogenase (DPD) activity, hence an index of 5
fluorouracil (5-FU) response and toxicity. Studies have re-affirmed the value of
5-FU and 5,6-dihydro-5-fluorouracil (FUH2) for therapeutic drug monitoring (TDM).
However, FUH2 has limited stability in plasma, necessitating expedited plasma
separation and freezing, where routine compliance may not be easy. The
metabolites alpha-fluoro-beta-ureidopropionic acid (FUPA) and alpha-fluoro-beta
alanine (FbetaAL) are stable in plasma and are probable candidates for TDM. This
paper describes development, validation and application of an LC-MS/MS assay
quantifying U, UH2, 5-FU, FUH2, FUPA and FbetaAL in human plasma. Extraction was
by salt-assisted liquid-liquid extraction (LLE) in two-stages with pH adjustment.
The supernatants were mixed, dried and reconstituted. Analytes were resolved on
the Luna PFP (2) (150*2.00mm, 3MU) column by gradient elution and analyzed by
tandem mass spectrometry via electrospray ionisation in positive polarity. The
analytical response was linear (r2>=0.99) in the concentration (ng/mL) ranges: 50
10 000 for FbetaAL and FUH2, 50-5 000 for FUPA, 50-100 000 for 5-FU, 5-200 for U
and 10-400 for UH2. Within- and between-run accuracy and precision were <= 10.2%
and <= 9.8% respectively across the QC range and inclusive of LLOQ. The internal
standard (IS) normalised matrix effects were within 93-112% with CV of <= 9.7%
and normalised recoveries were within 91-107% with CV of <= 9.8%. This robust
assay was successfully applied to samples from rectal and colorectal cancer
patients (n=10) on 5-FU. Deviations <= 2.0% from the mean values were observed
when incurred samples were reanalysed.
PMID- 28501751
TI - The state of everyday quantitative EEG use in Canada: A national technologist
survey.
AB - PURPOSE: This study sought to determine the state of quantitative EEG (QEEG) use
in Canada, as QEEG may provide a partial solution to the issue of escalating EEG
demand against insufficient health care resources. METHODS: A 10-item survey
questionnaire was administered to participants at the annual meeting of the
Canadian Association of Electroneurophysiology Technologists, which was held in
parallel with the annual meeting of the Canadian Neurological Sciences
Federation. RESULTS: At least 70% of the Canadian population has QEEG access
through academic medical institutions with applicability to adults and children.
QEEG was clinically used 50% in real-time and 50% retrospectively in the critical
care and epilepsy monitoring units for long-term monitoring and automated seizure
detection. QEEG trend use, montage use, and duration were variable. CONCLUSION:
To cope with insufficient health care resources, QEEG is in surprisingly frequent
clinical use across Canada. There is no consensus on optimal QEEG trends and
montages. The relative ubiquity of QEEG affords an excellent opportunity for
research as increasing EEG demand outpaces dwindling health care resources into
the foreseeable future.
PMID- 28501752
TI - Effects of dust, formaldehyde and delayed feeding on early postnatal development
of broiler chickens.
AB - We investigated effects of perinatal exposure to dust or formaldehyde and the
moment of first feed intake after hatching on broiler chicken development during
the first week of life. Four environmental treatments were used from 468 until
512h of incubation: control (CONT), heat treated dust (HTD), untreated dust (UTD)
or formaldehyde disinfection (FORM). After hatching, all chickens were assigned
to 1 of 2 feeding treatments: early feeding (EF; feed and water available in the
hatcher) or delayed feeding (DF). After 512h of incubation (day 0), chickens were
reared until day 7 of age. In DF chickens, body weight (BW), yolk free body mass
(YFBM) and relative liver weight did not differ among environmental treatments at
day 0. However, in EF chickens BW at day 0 was greater in HTD chickens than in
UTD and FORM chickens. YFBM in EF chickens at day 0 was greater when chickens
were exposed to HTD compared to the other environmental treatments. In EF
chickens, relative liver weight was greater in HTD chickens than in FORM. In DF
chickens, BW at day 0 was positively related with hatching time (HT). In EF
chickens, YFBM was positively related to HT. Residual yolk weight at day 0 was
positively related with HT, whereas relative liver weight and microbicidal
capacity were negatively related with HT. This study demonstrated that
formaldehyde and dust during the hatching phase affect broiler chicken
development at pulling from the incubator, but not at day 7.
PMID- 28501753
TI - Relevance of cutoff on a 4th generation ELISA performance in the false positive
rate during HIV diagnostic in a low HIV prevalence setting.
AB - BACKGROUND: Despite the high specificity of fourth-generation enzyme immunoassays
(4th-gen-EIA) for screening during HIV diagnosis, their positive predictive value
is low in populations with low HIV prevalence. Thus, screening should be
optimized to reduce false positive results. OBJECTIVES: The influence of sample
cutoff (S/CO) values by a 4th-gen-EIA with the false positive rate during the
routine HIV diagnosis in a low HIV prevalence population was evaluated. STUDY
DESIGN: A total of 30,201 sera were tested for HIV diagnosis using Abbott
Architect(r) HIV-Ag/Ab-Combo 4th-gen-EIA at a hospital in Spain during 17 months.
Architect S/CO values were recorded, comparing the HIV-1 positive results
following Architect interpretation (S/CO>=1) with the final HIV-1 diagnosis by
confirmatory tests (line immunoassay, LIA and/or nucleic acid test, NAT). ROC
curve was also performed. RESULTS: Among the 30,201 HIV performed tests, 256
(0.85%) were positive according to Architect interpretation (S/CO>=1) but only
229 (0.76%) were definitively HIV-1 positive after LIA and/or NAT. Thus, 27
(10.5%) of 256 samples with S/CO>=1 by Architect were false positive diagnose.
The false positive rate decreased when the S/CO ratio increased. All 19 samples
with S/CO <=10 were false positives and all 220 with S/CO>50 true HIV-positives.
The optimal S/CO cutoff value provided by ROC curves was 32.7. No false negative
results were found. CONCLUSIONS: We show that very low S/CO values during HIV-1
screening using Architect can result HIV negative after confirmation by LIA and
NAT. The false positive rate is reduced when S/CO increases.
PMID- 28501754
TI - Expectant futures and an early diagnosis of Alzheimer's disease: Knowing and its
consequences.
AB - Efforts to diagnose Alzheimer's disease (AD) at earlier stages as a means to
managing the risks of an ageing population, dominate scientific research and
healthcare policy in the UK. It is anticipated that early diagnosis will maximise
treatment options and enable patients to 'prepare for their future' in terms of
care. Drawing on qualitative data gathered across an out-patient memory service
and in-patient hospital in the UK, the purpose of this paper is to examine the
ways in which the hopeful promissory claims of early diagnosis as it maintains
the dominant biomedical model for managing AD, are negotiated by healthcare
practitioners. Developing the analytical standpoint of the sociology of
expectations, this paper demonstrates that early diagnosis has the potential to
'close off' hopeful promissory visions of the future in two ways. Firstly, it
(re)produces the fearful anticipations of AD built around expectations concerning
the ageing future 'self', and secondly it produces uncertainty in terms of the
availability of care as material resource. Whilst practitioners account for the
uncertainties and anxieties it produces for patients and their families, they
also convey a sense of ambivalence concerning early diagnosis. This article
captures the internal conflicts and contradictions inherent to practitioners'
perspectives regarding the repercussions of early diagnosis and concludes by
arguing that it effaces the uncertainties and anxieties that it produces in
practice as it restricts the co-existence of narratives for making sense of
memory loss beyond 'loss of self', and fails to recognise care as a viable
alternative for managing AD.
PMID- 28501755
TI - New challenges for verbal autopsy: Considering the ethical and social
implications of verbal autopsy methods in routine health information systems.
AB - Verbal autopsy (VA) methods are designed to collect cause-of-death information
from populations where many deaths occur outside of health facilities and where
death certification is weak or absent. A VA consists of an interview with a
relative or carer of a recently deceased individual in order to gather
information on the signs and symptoms the decedent presented with prior to death.
These details are then used to determine and assign a likely cause-of-death. At a
population level this information can be invaluable to help guide prioritisation
and direct health policy and services. To date VAs have largely been restricted
to research contexts but many countries are now venturing to incorporate VA
methods into routine civil registration and vital statistics (CRVS) systems.
Given the sensitive nature of death, however, there are a number of ethical,
legal and social issues that should be considered when scaling-up VAs,
particularly in the cross-cultural and socio-economically disadvantaged
environments in which they are typically applied. Considering each step of the VA
process this paper provides a narrative review of the social context of VA
methods. Harnessing the experiences of applying and rolling out VAs as part of
routine CRVS systems in a number of low and middle income countries, we identify
potential issues that countries and implementing institutions need to consider
when incorporating VAs into CRVS systems and point to areas that could benefit
from further research and deliberation.
PMID- 28501756
TI - Dangertalk: Voices of abortion providers.
AB - Researchers have described the difficulties of doing abortion work, including the
psychosocial costs to individual providers. Some have discussed the self
censorship in which providers engage in to protect themselves and the pro-choice
movement. However, few have examined the costs of this self-censorship to public
discourse and social movements in the US. Using qualitative data collected during
abortion providers' discussions of their work, we explore the tensions between
their narratives and pro-choice discourse, and examine the types of stories that
are routinely silenced - narratives we name "dangertalk". Using these data, we
theorize about the ways in which giving voice to these tensions might transform
current abortion discourse by disrupting false dichotomies and better reflecting
the complex realities of abortion. We present a conceptual model for dangertalk
in abortion discourse, connecting it to functions of dangertalk in social
movements more broadly.
PMID- 28501757
TI - Subjective social status and premedical students' attitudes towards medical
school.
AB - Although students from lower socioeconomic backgrounds are more likely to depart
from the medical education pipeline, little is known about how premedical
students' social origins influence the adversities they face, the resources they
possess, or the internal struggles they confront in deciding whether or not to
pursue a career in medicine. Using original data collected from premedical
students at a flagship state university in the Midwest (N = 364), this study
explores how subjective social status shapes students' reservations about medical
school attendance and their perceptions of external pressure to pursue a career
in medicine. Status-based discrepancies in financial strains, social capital, and
interpersonal stressors-and the degree to which variation across these measures
mediates status differences in medical school outlook-are also explored. Net of
objective measures of social class, results suggest that doubts about attending
medical school and feeling that not attending medical school will let down one's
community are more prevalent among premeds who identify as lower status. These
group differences are explained-at least in part-by lower status premedical
students' perceptions of financial hardships, more limited reserves of social
capital, and more frequent encounters with class-based discrimination and with
educators who discourage their career aspirations.
PMID- 28501758
TI - Modulating anosognosia for hemiplegia: The role of dangerous actions in emergent
awareness.
AB - Anosognosia for hemiplegia is a lack of awareness of motor deficits following a
right hemisphere lesion. Residual forms of awareness co-occur with an explicit
denial of hemiplegia. The term emergent awareness refers to a condition in which
awareness of motor deficits is reported verbally during the actual performance of
an action involving the affected body part. In this study, two tasks were used to
explore the potential effects of i) attempting actions which are impossible for
sufferers of hemiplegia and ii) attempting actions which are potentially
dangerous. Sixteen hemiplegic patients (8 anosognosic, and 8 non-anosognosic)
were asked to perform both potentially dangerous and neutral actions. Our results
confirm an increase in emergent awareness in anosognosic patients during the
execution of both of these types of action. Moreover, actions that are
potentially dangerous improved the degree of awareness. However, lesions in the
fronto-temporal areas appear to be associated with a reduced effect of action
execution (emergent awareness) while lesions in the basal ganglia and amygdale
and the white matter underlying the insula and fronto-temporal areas are
associated with a lesser degree of improvement resulting from attempting to
perform dangerous actions.
PMID- 28501759
TI - Resource utilization for non-operative cervical radiculopathy: Management by
surgeons versus non-surgeons.
AB - OBJECTIVES: To compare the estimated resource utilization for non-operative
treatment of cervical radiculopathy if managed by surgeons versus non-surgeons.
PATIENTS AND METHODS: A Cervical Spine Research Society-sponsored survey was
administered at a national spine surgery conference to surgeons and non-surgeons,
as classified above. The survey asked questions regarding resource utilization
and perceived costs for the "average patient" with cervical radiculopathy managed
non-operatively. Resource utilization and perceived costs were compared between
surgeon and non-surgeon participants, and between private practice and academic
and/or hybrid groups that combine academic and private practices. RESULTS: In
total, 101 of the 125 conference attendees participated in the survey (return
rate 80.8%, of which 60% were surgeons). Surgeon and non-surgeon estimates for
duration of non-operative care did not differ (3.3 versus 4.2 months, p=0.071).
Estimates also did not differ for estimated number of physical therapy visits
(10.5 versus 10.5, p=0.983), cervical injections (1.4 versus 1.7, p=0.272),
chiropractic visits (3.1 versus 3.7, p=0.583), or perceived days off from work
(14.9 versus 16.3, p=0.816). The only difference identified was that surgeon
estimates of the number of physician visits while providing non-operative care
were lower than non-surgeon estimates (3.2 versus 4.0, p=0.018). In terms of
estimated costs, surgeon and non-surgeon were mostly similar (only difference
being that surgeon estimates for the total cost of physician visits per patient
were lower than non-surgeon estimates ($382 versus $579, p=0.007). Surgeon
estimates for the percent of their patients that go on to receive surgery within
6 months were higher than non-surgeon estimates (28.6% versus 18.8%, p=0.018).
Similarly, surgeon estimates for the percent of their patients to go on to
receive surgery within 2 years were higher than non-surgeon estimates (37.8%
versus 24.8%, p=0.013). Academic/hybrid and private practice group resource
utilization estimates and costs were also compared, and no significant
differences were found in any comparisons. Additionally, no significant
differences were found in these groups for duration of non-operative care, or the
estimates of the percent of patients who go on to receive surgery within 6 months
or two years. CONCLUSION: These data suggest that patients with cervical
radiculopathy managed by surgeons and those by non-surgeons have overall similar
resource utilization during a non-operative trial. This suggests that relatively
similar care is provided regardless of whom initiates the non-operative trial
(surgeon or non-surgeon). Although surgeons thought their patients more likely to
undergo surgery following a non-operative trial, this may be a bias due to
patient referral-specifically, surgeons may be more likely than non-surgeons to
manage patients with more severe or longer-standing radiculopathy.
PMID- 28501761
TI - Improving the quality of the intensive care follow-up of ventilated patients
during a national registration program.
AB - OBJECTIVES: The Belgian Public Health Organization is concerned with rates of
hospital-acquired infections like ventilator-associated pneumonia (VAP).
Implementing best practice guidelines for these nosocomial infections has
variable success in the literature. This retrospective study was undertaken to
see whether implementation of the evidence-based practices as a bundle was
feasible, would influence compliance, and could reduce the rates of VAP. STUDY
DESIGN: We utilized easily collectable data about regular care to rapidly assess
whether interventions already in place were effectively successfully applied.
This avoided cumbersome data collection and review. METHODS: Retrospective
compliance rates and VAP ratios were compared using z tests with P-values < 0.05
considered statistically significant. This data review attempted to examine the
impact of education campaigns, staff meetings, in-services, physician checklist,
nurse checklist, charge nurse checklist implementation, systematic VAP bundle
application, and systematic protocols for oral care and sedation protocols.
Additionally, VAP ratio could be registered by the participating centers.
RESULTS: A total of 10,211 intensive care unit (ICU) patients were included in
the study which represents 66,817 ICU days under artificial ventilation with an
endotracheal tube. The general compliance for VAP bundle raised from VAP was 61%
in February 2012 and 74.16% in December 2012 (P < 0.001). The incidence rate of
VAP went from 8.34 occurrences/1000 vent days in 2009 to 4.78 occurrences/1000
vent days in 2012 (P < 0.001-Pearson test). CONCLUSIONS: Efforts to improve
physician and staff education, and checklist implementation resulted in an
increase in compliance for VAP bundle and a decrease in VAP ratio. This study
confirms the applicability of best practice guidelines about regular care but
results on VAP incidence have to be confirmed.
PMID- 28501760
TI - Stromal PDGFR-alpha Activation Enhances Matrix Stiffness, Impedes Mammary Ductal
Development, and Accelerates Tumor Growth.
AB - The extracellular matrix (ECM) is critical for mammary ductal development and
differentiation, but how mammary fibroblasts regulate ECM remodeling remains to
be elucidated. Herein, we used a mouse genetic model to activate platelet derived
growth factor receptor-alpha (PDGFRalpha) specifically in the stroma.
Hyperactivation of PDGFRalpha in the mammary stroma severely hindered pubertal
mammary ductal morphogenesis, but did not interrupt the lobuloalveolar
differentiation program. Increased stromal PDGFRalpha signaling induced mammary
fat pad fibrosis with a corresponding increase in interstitial hyaluronic acid
(HA) and collagen deposition. Mammary fibroblasts with PDGFRalpha hyperactivation
also decreased hydraulic permeability of a collagen substrate in an in vitro
microfluidic device assay, which was mitigated by inhibition of either PDGFRalpha
or HA. Fibrosis seen in this model significantly increased the overall stiffness
of the mammary gland as measured by atomic force microscopy. Further, mammary
tumor cells injected orthotopically in the fat pads of mice with stromal
activation of PDGFRalpha grew larger tumors compared to controls. Taken together,
our data establish that aberrant stromal PDGFRalpha signaling disrupts ECM
homeostasis during mammary gland development, resulting in increased mammary
stiffness and increased potential for tumor growth.
PMID- 28501762
TI - Poorly differentiated gastro-entero-pancreatic neuroendocrine carcinomas: Are
they really heterogeneous? Insights from the FFCD-GTE national cohort.
AB - BACKGROUND: Diagnosis and management of poorly differentiated gastro-entero
pancreatic (GEP) neuroendocrine carcinomas (NECs) remain challenging. Recent
studies suggest prognostic heterogeneity. We designed within the French Group of
Endocrine Tumours a prospective cohort to gain insight in the prognostic
stratification and treatment of GEP-NEC. PATIENTS AND METHODS: All patients with
a diagnosis of GEP-NEC between 1st January 2010 and 31st December 2013 could be
included in this national cohort. Adenoneuroendocrine tumours were excluded.
RESULTS: 253 patients from 49 centres were included. Median age was 66 years.
Main primary locations were pancreas (21%), colorectal (27%), oesophagus-stomach
(18%); primary location was unknown in 20%. Tumours were metastatic at diagnosis
in 78% of cases. Performance status (PS) at diagnosis was 0-1 in 79% of patients.
Among the 147 (58%) cases reviewed by an expert pathological network, 39% were
classified as small cell NEC and 61% as large cell NEC. Median Ki67 index was 75%
(range, 20-100). Median overall survival was 15.6 (13.6-17.0) months. Significant
adverse prognostic factors in univariate analysis were PS > 1 (hazard ratio [HR]
= 2.5), metastatic disease (HR = 1.6), NSE>2 upper limit of normal [ULN]; HR =
3.2), CgA>2 ULN (HR = 1.7) and lactate dehydrogenase >2 ULN (HR = 2.1). After
first-line palliative chemotherapy (CT1) with platinum-etoposide (n = 152),
objective response, progression-free survival and overall survival were 50%, 6.2
and 11.6 months; they were 24%, 2.9 and 5.9, respectively, after post-CT1 FOLFIRI
regimen (n = 72). CONCLUSIONS: We report a large prospective series of GEP-NEC
which show the predominance of large cell type and advanced stage at diagnosis.
Prognosis was found more homogeneous than previously reported, mainly impacted by
PS and tumour burden.
PMID- 28501763
TI - Optimal duration of adjuvant chemotherapy for high-risk node-negative (N-) breast
cancer patients: 6-year results of the prospective randomised multicentre phase
III UNICANCER-PACS 05 trial (UCBG-0106).
AB - PURPOSE: Optimal duration of adjuvant chemotherapy in the treatment of early
stage breast cancer remained to be investigated rigorously for the standard
regimens in widespread use in North America (doxorubicin/cyclophosphamide, AC)
and Europe (5-fluorouracil/epirubicin/cyclophosphamide, FEC). Whether six cycles
of FEC 100 present an advantage, or not, compared with only four cycles was
tested directly in a phase III prospective multicentre trial. PATIENTS AND
METHODS: Between 2002 and 2006, 1515 women between 18 and 65 degrees years of
age, with node negative N(-) high-risk early-stage breast cancer, were included
in the study following breast surgery and axillary lymph node dissection or
procedure by sentinel node technique. Inclusion in the study required tumour size
T >= 1 cm and at least one of the high-risk factors: T > 2 cm, negative oestrogen
receptor/progesterone receptor (ER- and PR-), Scarff-Bloom-Richardson (SBR) grade
II or III and age <= 35 degrees years. Patients were randomly assigned to either
six FEC 100 (Arm A) or four FEC 100 (Arm B). The trial was powered to detect an
absolute difference >=6% in disease-free survival (DFS) at 5 degrees years.
RESULTS: At 6.1 degrees years median follow-up, with 91 (12%) events recorded in
Arm A versus 106 (14%) in Arm B, no statistically significant risk increase was
associated with four versus six FEC 100: DFS (hazard ratio (HR) = 1.18; CI 95%
[0.89-1.56], P = .24) and overall survival (OS) (HR = 1.39; CI 95% [0.91-2.13], P
= .12). CONCLUSION: Differences in chemotherapy duration did not induce notably
different outcomes in our cohort of high-risk patients. CLINICAL TRIAL REGISTRY
NUMBER: NCT00055679, Agence National de Securite du Medicament (ANSM) - France.
PMID- 28501764
TI - Open-label, multicentre safety study of vemurafenib in 3219 patients with
BRAFV600 mutation-positive metastatic melanoma: 2-year follow-up data and long
term responders' analysis.
AB - BACKGROUND: The orally available BRAF kinase inhibitor vemurafenib is an
effective and tolerable treatment option for patients with metastatic melanoma
harbouring BRAFV600 mutations. We assessed the safety of vemurafenib in a large
population of patients with few alternative treatment options; we report updated
2-year safety. METHODS: This was an open-label, multicentre study of vemurafenib
(960 mg bid) in patients with previously treated or untreated BRAF mutation
positive metastatic melanoma (cobas(r) 4800 BRAF V600 Mutation Test). The primary
end-point was safety; efficacy end-points were secondary. An exploratory analysis
was performed to assess safety outcomes in patients with long duration of
response (DOR) (>=12 or >=24 months). RESULTS: After a median follow-up of 32.2
months (95% CI, 31.1-33.2 months), 3079/3219 patients (96%) had discontinued
treatment. Adverse events (AEs) were largely consistent with previous reports;
the most common all-grade treatment-related AEs were arthralgia (37%), alopecia
(25%) and hyperkeratosis (23%); the most common grade 3/4 treatment-related AEs
were squamous cell carcinoma of the skin (8%) and keratoacanthoma (8%). In the
exploratory analysis, patients with DOR >=12 months (n = 287) or >=24 months (n =
133) were more likely to experience grade 3/4 AEs than the overall population. No
new specific safety signals were observed with longer vemurafenib exposure.
CONCLUSIONS: After 2 years' follow-up, safety was maintained in this large group
of patients with BRAFV600 mutation-positive metastatic melanoma who are more
representative of routine clinical practice than typical clinical trial
populations. These data suggest that long-term vemurafenib treatment is effective
and tolerable without the development of new safety signals.
PMID- 28501765
TI - Enhanced sublingual immunotherapy by TAT-fused recombinant allergen in a murine
rhinitis model.
AB - Allergen-specific sublingual immunotherapy (SLIT) is well known as an effective
and non-invasive route to induce allergy desensitization. The goal of this study
was to investigate whether a TAT-fused recombinant allergen could enhance SLIT
efficacy. BALB/c mice sensitized to the main allergen (Che a 3) of Chenopodium
album pollen were treated sublingually either with rChe a 3 (100MUg/dose) or rTAT
Che a 3 (100MUg/dose), two times per week for eight weeks. SLIT with rTAT-Che a 3
led to significantly greater allergen-specific IgG2a than rChe a 3; however,
neither rTAT-Che a 3 nor rChe a 3 affected allergen-specific IgE or IgG1 antibody
levels. In addition, interleukin 4 (IL-4) levels in re-stimulated splenocytes
from the rTAT-Che a 3 mice were significantly lower than in those from the rChe a
3 mice, while interferon-gamma (IFN-gamma) was significantly greater in the rChe
a 3 mice than in the rTAT-Che a 3 mice. Furthermore, sublingual administration of
rTAT-Che a 3 induced significantly greater TGF-beta secretion in re-stimulated
splenocytes than administration of rChe a 3. Accordingly, SLIT with rTAT-Che a 3
led to significantly greater expression of TGF-beta- and Foxp3-specific mRNAs in
the splenocytes than in those from the rChe a 3 mice. Our findings demonstrate
that TAT-fused rChe a 3 suppressed the allergic response through preferential
enhancement of systemic regulatory T-cell (Treg)-mediated immunity responses,
likely by facilitating allergen capture and presentation by sublingual Langerhans
like dendritic cells.
PMID- 28501766
TI - Therapeutic effects of zerumbone in an alkali-burned corneal wound healing model.
AB - Cornea is an avascular transparent tissue. Ocular trauma caused by a corneal
alkali burn induces corneal neovascularization (CNV), inflammation, and fibrosis,
leading to vision loss. The purpose of this study was to examine the effects of
Zerumbone (ZER) on corneal wound healing caused by alkali burns in mice. CNV was
induced by alkali-burn injury in BALB/C female mice. Topical ZER (three times per
day, 3MUl each time, at concentrations of 5, 15, and 30MUM) was applied to treat
alkali-burned mouse corneas for 14 consecutive days. Histopathologically, ZER
treatment suppressed alkali burn-induced CNV and decreased corneal epithelial
defects induced by alkali burns. Corneal tissue treated with ZER showed reduced
mRNA levels of pro-angiogenic genes, including vascular endothelial growth
factor, matrix metalloproteinase-2 and 9, and pro-fibrotic factors such as alpha
smooth muscle actin and transforming growth factor-1 and 2. Immunohistochemical
analysis demonstrated that the infiltration of F4/80 and/or CCR2 positive cells
was significantly decreased in ZER-treated corneas. ZER markedly inhibited the
mRNA and protein levels of monocyte chemoattractant protein-1 (MCP-1) in human
corneal fibroblasts and murine peritoneal macrophages. Immunoblot analysis
revealed that ZER decreased the activation of signal transducer and activator of
transcription 3 (STAT3), with consequent reduction of MCP-1 production by these
cells. In conclusion, topical administration of ZER accelerated corneal wound
healing by inhibition of STAT3 and MCP-1 production.
PMID- 28501767
TI - Garlic-derived organosulfur compound exerts antitumor efficacy via activation of
MAPK pathway and modulation of cytokines in SGC-7901 tumor-bearing mice.
AB - Diallyl trisulfide (DATS), a natural agent derived from garlic, has been tested
for its antigastric cancer activities in various preliminary studies. However,
more systematic pharmacodymatic (PD) and mechanistic evaluations are clearly
needed. The aim of this study was to investigate the antitumor effects of DATS in
the treatment of human gastric cancer cell SGC-7901 both in vitro and in vivo
using widely recommended study procedures. DATS suppressed cancer cells
proliferation and induced cell cycle arrest accompanied by an increase in the
expressions of cyclin A2 and cyclin B1 in SGC-7901 cancer cells. DATS also caused
an increase in apoptotic cell death, which involved in accumulations of bax, p53,
and cytochrome C and reduction of Bcl-2 expressions. Besides, activation of JNK,
ERK and p38 phosphorylation in DATS-treated cells suggested that mitogen
activated protein kinase (MAPKs) pathways were involved in DATS-induced
apoptosis. Meanwhile, DATS significantly inhibited tumor growth and promoted
tumor apoptosis in a xenograft model of gastric cancer cell SGC-7901. DATS
inhibited tumor migration and invasion by modulating MMP9 and E-cadherin protein
expressions. In addition, DATS treatment evidently increased the cytokine
secretions of IL-12, TNF-alpha and IFN-gamma (p<0.05). Biochemical serum analysis
and histopathological examination indicated no obvious side effects in major
mouse organs. Therefore, our findings provide a framework for further exploration
of DATS as a novel chemotherapeutic for human gastric cancer.
PMID- 28501769
TI - Dietary exposure assessment for arsenic and mercury following submarine tailings
placement in Ratatotok Sub-district, North Sulawesi, Indonesia.
AB - The Mesel gold mine in the Ratatotok Sub-district operated between 1996 and 2004
with tailings disposal via an engineered submarine tailings placement (STP) into
Buyat Bay. This operation raised concerns of increased levels of arsenic (As) and
mercury (Hg) associated disease in the local communities from consumption of
seafood contaminated with anthropogenic As and Hg. This report uses the dietary
exposure to As and Hg, from local fishermen and market-purchased Codex "as
consumed" and environmental fish results from the pre-mining baseline (1990
1995), the mine operational (1996-2004) and post-closure monitoring (2007-2016)
to examine the potential health effects. The Ratatotok Sub-district consumers
total As average daily intake from fish was between 152 and 317 MUg/day (adults)
and 58 and 105 MUg/day (infants). The average daily intake of inorganic arsenic
(Asi) from the dietary staples fish and rice and drinking water consumption was
77 MUg/day (adults) and 35 MUg/day (infants) at Buyat Pantai and 39 MUg/day
(adults) and 19 MUg/day (infants) at Ratatotok township. Fish consumption
contributed 8.2% (adults) and 6.5% (infants) to total daily Asi intake. Average
Hg intake from fish consumption, exceeded the FAO WHO PTWI for methylmercury
(MeHg) for all age and gender groups at Buyat Pantai 4.6 MUg/kg bw/wk (adults)
and 7.3 MUg/kg bw/wk (infants) and for the infants at Buyat village and Ratatotok
township (2.5 and 2.8 MUg/kg bw/wk respectively). The Manado City consumers had
average intakes below the MeHg PTWI. The Hg exceedances resulted from the high
fish consumption in coastal communities and not elevated levels of Hg in fish. Hg
exposure levels from the pre-mining baseline, Mesel STP operation and post
closure monitoring, confirmed that exceedances were unrelated to the tailings
deposited into Buyat Bay.
PMID- 28501768
TI - Association between Chinese cooking oil fumes and sleep quality among a middle
aged Chinese population.
AB - Poor sleep quality is an important symptom of many medical or psychiatric
disorders. However, the impact of cooking oil fumes (COFs) on sleep quality has
not been studied. This population-based cross-sectional study was conducted to
examine the association between COFs of Chinese household cooking and sleep
quality. Individual sleep quality assessment was completed in 2197 participants
with an average age of 37.52 years, through Pittsburgh Sleep Quality Index
(PSQI). Information about their cooking practice were also collected by self
reported questionnaire. As an internal biomarker of COFs, urinary 1-hydroxypyrene
(1-HOP) (n = 562) was further measured using high-performance liquid
chromatography. Binary logistic regression models were performed to evaluate the
association between exposure to COFs and individual sleep quality. We found that,
subjective poor kitchen ventilation, preheating oil to smoking, and cooking for
over 30 minutes were positively associated with overall poor sleep quality
(global PSQI score >5) [odds ratio (OR) = 1.75, 95% confidence interval (CI) =
1.43-2.16; 1.25, (1.03-1.52); 1.42, (1.15-1.76), respectively]. After adjusting
for potential confounders, subjective poor kitchen ventilation still tend to
increase the risk of long sleep latency, sleep disturbances, and daytime
dysfunction [OR = 1.37, 95% CI = 1.09-1.73; 1.91, (1.39-2.61); 1.54, (1.23-1.93),
respectively]. Similar results were observed in participants who preheated oil to
smoking [OR = 1.36, 95% CI = 1.08-1.72; 1.55, (1.14-2.14); 1.25, (1.02-1.55),
respectively] and cooked for over 30 minutes [OR = 1.34, 95% CI = 1.05-1.72;
1.46, (1.03-2.06); 1.36, (1.08-1.72), respectively]. Furthermore, high urinary 1
HOP level was also positively associated with overall poor sleep quality (OR =
2.30, 95% CI = 1.31-4.05). The results indicated that exposure to COFs from
Chinese household cooking may be a risk factor for poor sleep quality among
middle-aged Chinese population.
PMID- 28501770
TI - Effect of limestone, lignite and biochar applied alone and combined on cadmium
uptake in wheat and rice under rotation in an effluent irrigated field.
AB - Cadmium (Cd) uptake and accumulation in crop plants, especially in wheat
(Triticum aestivum) and rice (Oryza sativa) is one of the main concerns for food
security worldwide. A field experiment was done to investigate the effects of
limestone, lignite, and biochar on growth, physiology and Cd uptake in wheat and
rice under rotation irrigated with raw effluents. Initially, each treatment was
applied alone at 0.1% and combined at 0.05% each and wheat was grown in the field
and then, after wheat harvesting, rice was grown in the same field without
additional application of amendments. Results showed that the amendments applied
increased the grain and straw yields as well as gas exchange attributes compared
to the control. In both crops, highest Cd concentrations in straw and grains and
total uptake were observed in control treatments while lowest Cd concentrations
was observed in limestone + biochar treatment. No Cd concentrations were detected
in wheat grains with the application of amendments except limestone (0.1%). The
lowest Cd harvest index was observed in limestone + biochar and lignite + biochar
treatments for wheat and rice respectively. Application of amendments decreased
the AB-DTPA extractable Cd in the soil while increasing the Cd immobilization
index after each crop harvest. The benefit-cost ratio and Cd contents in plants
revealed that limestone + biochar treatment might be an effective amendment for
increasing plant growth with lower Cd concentrations.
PMID- 28501771
TI - Mechanisms of efficient As solubilization in soils and As accumulation by As
hyperaccumulator Pteris vittata.
AB - Arsenic (As) in soils is of major environmental concern due to its ubiquity and
carcinogenicity. Pteris vittata (Chinese brake fern) is the first known As
hyperaccumulator, which is highly efficient in extracting As from soils and
translocating it to the fronds, making it possible to be used for
phytoremediation of As-contaminated soils. In addition, P. vittata has served as
a model plant to study As metabolisms in plants. Based on the recent advances, we
reviewed the mechanisms of efficient As solubilization and transformation in
rhizosphere soils of P. vittata and effective As uptake, translocation and
detoxification in P. vittata. We also provided future research perspectives to
further improve As phytoremediation by P. vittata.
PMID- 28501772
TI - Hyperoside protects against chronic mild stress-induced learning and memory
deficits.
AB - Hyperoside (quercetin-3-O-b-d-galactosidepyranose) is a plant-derived flavonoid
mainly found in fruits, fruit juices (most notably flavanols, flavanones, and
anthocyanins) and Chinese traditional medicines. It has been applied to relieve
pain and improve cardiovascular functions in clinic. However, the effects of
hyperoside on cognitive impairment induced by chronic stress and the underlying
molecular mechanisms remain unclear. In the current study, we used chronic mild
stress (CMS) rats to investigate the effects of hyperoside on learning and memory
and further explore the possible mechanisms. Our results demonstrated that
hyperoside reduced the escape latency and the swimming distance of CMS rats in
Morris water maze test and reversed depressive symptoms in forced swim test (FST)
and sucrose preference test. In addition, hyperoside increased the expression of
brain-derived neurotrophic factor (BDNF) in hippocampus of CMS rats without
influencing the corticosterone (CORT) level in blood plasma. Furthermore, K252a,
an inhibitor of the BDNF receptor TrkB, prevented the protective effects of
hyperoside on learning and memory in CMS rats. Taken together, these results
indicate that hyperoside reverses the cognitive impairment induced by CMS, which
is associated with the regulation of BDNF signaling pathway.
PMID- 28501774
TI - Tuning of major signaling networks (TGF-beta, Wnt, Notch and Hedgehog) by miRNAs
in human stem cells commitment to different lineages: Possible clinical
application.
AB - Two distinguishing characteristics of stem cells, their continuous division in
the undifferentiated state and growth into any cell types, are orchestrated by a
number of cell signaling pathways. These pathways act as a niche factor in
controlling variety of stem cells. The core stem cell signaling pathways include
Wingless-type (Wnt), Hedgehog (HH), and Notch. Additionally, they critically
regulate the self-renewal and survival of cancer stem cells. Conversely, stem
cells' main properties, lineage commitment and stemness, are tightly controlled
by epigenetic mechanisms such as DNA methylation, histone modifications and non
coding RNA-mediated regulatory events. MicroRNAs (miRNAs) are cellular switches
that modulate stem cells outcomes in response to diverse extracellular signals.
Numerous scientific evidences implicating miRNAs in major signal transduction
pathways highlight new crosstalks of cellular processes. Aberrant signaling
pathways and miRNAs levels result in developmental defects and diverse human
pathologies. This review discusses the crosstalk between the components of main
signaling networks and the miRNA machinery, which plays a role in the context of
stem cells development and provides a set of examples to illustrate the extensive
relevance of potential novel therapeutic targets.
PMID- 28501773
TI - TRPV4 functions in flow shear stress induced early osteogenic differentiation of
human bone marrow mesenchymal stem cells.
AB - Mechanical cues have been shown to induce osteogenic differentiation of bone
marrow stromal cells (MSCs). The TRPV4 channel, a Ca2+-permeable membrane ion
channel, is implicated in the transduction of external mechanical stimulation
into specific intracellular responses in a wide variety of bone cells. However,
the role of TRPV4 in transducing and regulating the differentiation of human MSCs
in response to flow shear stress (FSS) is unclear. In this study, using FSS and
calcium imaging, we demonstrated that FSS activated early osteogenic
differentiation, as shown by the early osteogenic differentiation marker osterix
(Osx) and alkaline phosphatase (ALP) staining. Increases in intracellular Ca2+
and in the percentage of responding cells were induced by FSS. However, the late
osteogenic differentiation marker Ocn and in vitro mineralization were unchanged
after FSS stimulation. TRPV4 channels mediated the FSS-induced Ca2+ influx and
osteogenic differentiation of MSCs, which were inhibited by a selective TRPV4
blocker HC-067047 and specific Trpv4 siRNA. Ca2+ influx through TRPV4 promoted
NFATc1 nuclear localization. These results identify an essential role of TRPV4 in
FSS-induced early osteogenic differentiation of human MSCs.
PMID- 28501775
TI - Vitamin D: Correlation with biochemical and body composition changes in a
southern Brazilian population and induction of cytotoxicity in mesenchymal stem
cells derived from human adipose tissue.
AB - Studies have shown that metabolic disorders, serum inflammatory markers and
weight gain (obesity) are correlated with vitamin D deficiency. Therefore, the
present study correlated the serum calcidiol (s25(OH)D3) levels in a sample of
individuals from southern Brazil with variables related to metabolic disorders,
obesity and lifestyle habits and assessed the cytotoxic effect of calcitriol on
adipose tissue-derived mesenchymal stem cells (ADSCs). The results showed a
79.23% prevalence of hypovitaminosis D in the study population and a correlation
(p<0.05) between a low serum vitamin D concentration and an elevated low-density
lipoprotein cholesterol (LDL-c) level. Univariate linear regression analysis
using 25(OH)D3 as a regressor showed a negative association (p<0.05) with an
indoor work environment (beta=-2.305), increased body fat (beta=-0.095), age
(beta=-0.065) and high-density lipoprotein cholesterol (HDL-c; beta=-0.109). An
in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay
performed with ADSCs using five calcitriol concentrations (15.625, 31.25, 62.5,
125 and 250nM) indicated cytotoxic potential (p<0.05) at the 62.5nM concentration
at 48 and 72h and at the 125 and 250nM concentrations at 24, 48 and 72h. The
results reported herein corroborate one another and suggest a key association
between vitamin D deficiency and the development of obesity because ADSCs are
involved in adipose tissue hyperplasia and differentiate into adipocytes that can
sequester the bioavailable vitamin D necessary for homeostasis.
PMID- 28501776
TI - Inhibition of SENP3 by URB597 ameliorates neurovascular unit dysfunction in rats
with chronic cerebral hypoperfusion.
AB - Disruption of the neurovascular unit (NVU), induced by chronic cerebral
hypoperfusion (CCH), has been broadly found in various neurological disorders.
SUMO-specific protease 3 (SENP3) is expressed in neurons, astrocytes, and
microglia, and regulates a variety of cell events. However, whether SENP3 is
involved in neurovascular injury under the condition of CCH is still elusive. To
address this issue, we investigated the effect of the fatty acid amide hydrolase
(FAAH) inhibitor URB597 on NVU and the role of SENP3 in this process, as well as
the underling mechanisms. The expression of SENP3 was detected by
immunochemistry. The function and structure of the NVU was assessed by Western
blot analysis and transmission electron microscopy. CCH caused the upregulation
of SENP3, the disruption of cell and non-cell components at the protein level
within the NVU, and ultrastructural deterioration. The NVU impairment as well as
overexpression of SENP3 were reversed by treatment with URB597. These results
reveal a novel neuroprotective role in URB597, which implicates URB597 in the
amelioration of CCH-induced NVU impairment by inhibiting SENP3.
PMID- 28501777
TI - MiR-140/BDNF axis regulates normal human astrocyte proliferation and LPS-induced
IL-6 and TNF-alpha secretion.
AB - Reactive astrocyte proliferation after spinal cord injury (SCI) contributes to
glial scar formation that impedes axonal regeneration. The mechanisms underlying
astrocyte proliferation upon injury remain partially understood. MicroRNAs
(miRNAs) function as a major class of post-transcriptional gene expression
regulators that participate in many biological processes. In this study, we
focused on the functional role of miR-140 in normal human astrocyte (NHA) cell
proliferation. Ectopic miR-140 expression significantly inhibited NHA cell
viability and proliferation; miR-140 inhibition exerted the opposite function.
Commonly, miRNAs exert functions through targeting downstream genes to inhibit
their expression. In the present study, brain-derived neurotrophic factor (BDNF),
a regulator of astrocyte proliferation and differentiation, confirmed as a direct
target of miR-140 in NHA. Through binding to the 3'UTR of BDNF, miR-140 inhibited
BDNF expression. BDNF overexpression significantly promoted NHA cell viability
and proliferation; the regulatory effect of miR-140/BDNF on NHA proliferation was
mediated by PI3K/AKT pathway. Moreover, we evaluated the functional role of miR
140 in Lipopolysaccharide (LPS)-induced in vitro injury model of astroglial
cultures; a significantly up-regulated BDNF, interleukin (IL)-6 and tumor
necrosis factor (TNF)-alpha expression in response to LPS stimulation was
observed. After ectopic miR-140 expression, the promotive effect of LPS on BDNF,
IL-6 and TGF-alpha expression was partially restored. Taken together, miR
140/BDNF axis regulates NHA proliferation through PI3K/AKT pathway; miR-140 could
inhibit BDNF, IL-6 and TGF-alpha expression in LPS-induced in vitro injury model.
MiR-140/BDNF might serve as a promising target in strategy against reactive
astrocyte proliferation after SCI.
PMID- 28501778
TI - Upregulation of the long non-coding RNA SNHG1 predicts poor prognosis, promotes
cell proliferation and invasion, and reduces apoptosis in glioma.
AB - Long non-coding RNAs (lncRNAs), which are non-coding RNAs with a length above 200
nucleotides, have emerged as novel and important gene expression modulators in
carcinogenesis. Recent evidence indicates that the lncRNA small nucleolar RNA
host gene 1 (SNHG1) functions as an oncogene in several types of human cancers.
However, its function in the development of glioma remains unknown. The aim of
this research was to investigate the clinical aspects and biological mechanisms
of SNHG1 in glioma. SNHG1 expression was measured in glioma tissues and cell
lines by quantitative real-time PCR (qRT-PCR). The association between SNHG1
expression in tissues and clinicopathological characteristics and prognosis in
glioma patients was also explored. Gain-of-function and loss-of-function studies
using SNHG1 cDNA and siRNA, respectively, were used to investigate the role of
SNHG1 in cell proliferation, invasion and apoptosis in glioma. SNHG1 was highly
expressed in glioma tissues, and its upregulation was closely related to old age.
Kaplan-Meier analysis showed that high expression of SNHG1 was significantly
associated with poor overall survival (OS). Functionally, ectopic expression of
SNHG1 enhanced cell proliferation and cell invasion and reduced cell apoptosis in
vitro, while SNHG1 knockdown reversed these effects. Taken together, our findings
indicate that SNHG1 functions as an oncogene in glioma and may serve as a novel
therapeutic target in future treatments.
PMID- 28501779
TI - Coenzyme Q10 improves the survival, mesenteric perfusion, organs and vessel
functions in septic rats.
AB - BACKGROUND: Coenzyme Q10 (CoQ10) is a naturally occurring, lipid-soluble
antioxidant and an essential electron carrier in the mitochondrial respiratory
chain. In sepsis, CoQ10 deficiency induced by mitochondrial failure can lead to
hypoxia, hypoperfusion, oxidative organ damage and finally death. We aimed to
investigate the effects of CoQ10 on survival, mesenteric artery blood flow
(MABF), vascular reactivity, oxidative and inflammatory injuries in cecal
ligation and puncture (CLP)-induced sepsis. METHODS: Wistar rats were divided
into Sham, CLP, Sham+CoQ10, CLP+CoQ10 subgroups. CoQ10 (10mg/kg/day) or vehicle
(olive oil; 1mL/kg/day) was intraperitoneally injected for 15days. At 16th day,
Sham or CLP operation was performed. 20h after the operations, MABF and
phenylephrine responses of isolated aortic rings were measured. Tissue samples
were obtained for histopathological and biochemical evaluations. Furthermore,
survival rates were monitored throughout 96h. RESULTS: CoQ10 prevented mesenteric
hypoperfusion and aortic dysfunction induced by CLP. Survival rate was %0 at 46th
h in CLP group, but in CLP+CoQ10 group it was 37.5% at the end of 96h. CLP
induced elevations of serum AST, ALT, LDH, BUN, Cr and inflammatory cytokine
(tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6) levels were
blocked by CoQ10. CoQ10 restored the increased liver, lung, spleen and kidney
malondialdehyde levels and as well as reduced liver and spleen glutathione
levels. The protective effects of CoQ10 on multiple organ damage were also
observed histopathologically. CONCLUSIONS: CoQ10 showed protective effects in
sepsis due to its preservative effects on mesenteric perfusion, aortic function
and also its anti-inflammatory and antioxidative effects.
PMID- 28501780
TI - Low power continuous wave-laser seed irradiation effect on Moringa oleifera
germination, seedling growth and biochemical attributes.
AB - Recently, laser application in agriculture has gained much attention since plant
characteristics were improved significantly in response of pre-sowing seed
treatment. Pre-sowing laser seed treatment effects on germination, seedling
growth and mineral profile were studied in Moringa olifera. M. olifera healthy
seeds were exposed to 25, 50, 75mJ low power continuous wave laser light and
grown under greenhouse conditions. The seedling growth and biochemical attributes
were evaluated from 10-day-old seedlings. The germination parameters (percentage,
mean germination time), vigor index, seedling growth (root length, seedling
length, shoot fresh weight, root fresh weight, shoot dry weight, root dry weight)
enhanced considerably. The laser energy levels used for seed irradiation showed
variable effects on germination, seedling growth and mineral profile. The mineral
contents were recorded to be higher in seedling raised from laser treated seeds,
which were higher in roots versus shoots and leaves. The effect of laser
treatment on seedling fat, nitrogen and protein content was insignificant and at
higher energy level both nitrogen and protein contents decreased versus control.
Results revealed that M. olifera germination, seedling growth and mineral
contents were enhanced and optimum laser energy level has more acceleratory
effect since at three laser energy levels the responses were significantly
different. Overall the laser energy levels effect on germination and seedling
growth was found in following order; 75mJ>50mJ>25mJ, where as in case of fat,
protein and nitrogen contents the trend was as; 25mJ>50mJ and 75mJ. However, this
technique could possibly be used to improve the M. olifera germination, seedling
growth, and minerals contents where germination is low due to unfavorable
conditions.
PMID- 28501781
TI - Green synthesis of Au-Cu2-xSe heterodimer nanoparticles and their in-vitro
cytotoxicity, photothermal assay.
AB - We demonstrate a new route for the synthesis of heterogeneous nanoparticles (NPs)
composed of a gold domain (Au) and a heavily doped semiconductor domain (Cu2-xSe)
which exhibit a broad localized surface plasmon resonance (LSPR) arising from
interactions between two nanocrystal domains. We also demonstrate the in-vitro
cytotoxicity and photo thermal efficiency of as prepared Au-Cu2-xSe heterodimer
nanoparticles. This work establishes a new way of tuning LSPR by engineering the
density of free charge carriers in two interacting domains.
PMID- 28501782
TI - Combination of the Electro/Fe3+/peroxydisulfate (PDS) process with activated
sludge culture for the degradation of sulfamethazine.
AB - In this paper, the major factors affecting the degradation and the mineralization
of sulfamethazine by Electro/Fe3+/peroxydisulfate (PDS) process (e.g. current
density, PDS concentration, Fe3+ ions concentration and initial sulfamethazine
(SMT) concentration) were evaluated. The relevance of this process as a
pretreatment prior to activated sludge culture was also examined. Regarding the
impact on SMT degradation and mineralization, the obtained results showed that
they were significantly enhanced by increasing the current density and the PDS
concentrations in the ranges 1-40mAcm-2 and from 1 to 10mM respectively; while
they were negatively impacted by an increase of the initial SMT concentration and
the Fe3+ concentration, from 0.18 to 0.36mM and from 1 to 4mM respectively. The
optimal operating conditions were therefore 40mAcm-2 current density, 10mM PDS
concentrations, 1mM Fe3+, and 0.18mM SMT. Indeed, under these conditions the
degradation of SMT and its mineralization yield were 100% and 83% within 20min
and 180min respectively. To ensure a significant residual organic content for
activated sludge culture after Electro/Fe3+/PDS pre-treatment, the
biodegradability test and the biological treatment were performed on a solution
electrolyzed at 40mAcm-2, 10mM PDS concentrations, 1mM Fe3+, and 0.36mM SMT.
Under these conditions the BOD5/COD ratio increased from 0.07 to 0.41 within 6h
of electrolysis time. The subsequent biological treatment increased the
mineralization yield to 86% after 30days, confirming the relevance of the
proposed combined process.
PMID- 28501783
TI - Silencing of DNA repair sensitizes pediatric brain tumor cells to gamma
irradiation using gold nanoparticles.
AB - We present a nanoparticle (NP)-mediated delivery vehicle that effectively carries
and protects siRNA in pediatric ependymoma (EP) and medulloblastoma (MB) cells.
The delivery vehicle consists of gold NPs coated with a polymeric shell
comprising polyethylene glycol (PG), chitosan and polyethyleneimine (Au-CP-PEI).
NPs loaded with siRNA knocked down Ape1 expression by over 75% in both MB and EP
cells. Further, this reduction in Ape1 expression is associated with an increase
in DNA damage after irradiation. The results indicate that NP-associated delivery
of siApe1 is a feasible approach to circumventing pediatric brain tumor
resistance to radiation therapy.
PMID- 28501784
TI - Cellular uptake mechanism and clearance kinetics of fluorescence-labeled
glycyrrhetinic acid and glycyrrhetinic acid-modified liposome in hepatocellular
carcinoma cells.
AB - Glycyrrhetinic acid (GA) is a natural pentacyclic triterpene derivative that
exerts significant effects in the suppression of liver cancer. The receptors of
GA on liver cells and hepatocellular carcinoma (HCC) cells have drawn broad
attention. The effects of GA might depend on its transport into and out of cells.
However, the question has not been previously addressed despite its obvious and
fundamental importance. In this paper, GA and GA-modified liposome (GA-Lip) were
labeled with fluorescein isothiocyanate (FITC) or coumarin 6 (Cou6) using
chemical or pharmaceutical techniques. The transport courses of FITC-GA and GA
Cou6-Lip were studied in HepG2 cells in vitro. We found that the fluorescence
labeled GA and GA-Lip uptake and clearance were time-dependent. FITC-GA uptake
involved passive diffusion and active transport, and the receptors were in the
cytomembrane proteins. GA-Cou6-Lip uptake was mediated by caveolae-dependent
endocytosis. In addition, FITC-GA and GA-Cou6-Lip clearance of the HCC cells
fitted exponential decay and second-order processes, respectively. These findings
provide new insights into the anti-HCC actions of GA.
PMID- 28501785
TI - Experimental study of sucralfate intervention for paraquat poisoning in rats.
AB - OBJECTIVE: This study explored the effects of sucralfate intervention as a novel
treatment for paraquat (PQ) poisoning in Sprague-Dawley (SD) rats. METHODS: After
PQ poisoning, the SD rats were randomly divided into the PQ control group
(treated with normal saline), the sodium bicarbonate (SB) treatment group, and
the sucralfate (LTL) treatment group. Then, the rats were administered normal
saline, sodium bicarbonate solution, or sucralfate suspension as an intervention
by gastric lavage. At 1, 3, 6, and 10days after poisoning, the left lungs of some
rats were removed to determine the lung wet/dry (W/D) weight ratio. Additionally,
the serum cytokine levels were measured, and the lung and kidney tissues were
pathologically examined. RESULTS: After treatment, the signs and symptoms of the
rats were improved, the mortality rate was reduced, the W/D weight ratio of the
lung was lower, the cytokine levels [transforming growth factor (TGF)-beta1,
interleukin (IL)-10, and tumor necrosis factor (TNF)-alpha] were decreased, and
the pathological injuries of the lungs and kidneys were improved. Moreover,
sucralfate was significantly more effective than the control (normal saline)
group and the SB treatment group. CONCLUSION: The results showed that early
gastrointestinal lavage with sucralfate effectively reduced the inflammatory
response and lung and kidney injuries and improved the survival of the SD rats.
PMID- 28501786
TI - QAC modified PVDF membranes: Antibiofouling performance, mechanisms, and effects
on microbial communities in an MBR treating municipal wastewater.
AB - Biofouling remains as a critical issue limiting the widespread applications of
membrane bioreactors (MBRs). The use of antibiofouling membranes is an emerging
method to tackle this issue. In this study, a polyvinylidene fluoride (PVDF)
membrane was modified using a quaternary ammonium compound (QAC) to create an
antibiofouling membrane. The membrane was used in an MBR and the performance,
mechanisms, and effects on microbial communities of this membrane were compared
to a control operated in parallel. Results showed that the membrane exhibited a
significantly reduced transmembrane pressure increase rate of 0.29 kPa/d compared
with 0.91 kPa/d of the control. Analysis using a confocal laser scanning
microscope (CLSM) revealed almost complete lack of living microbes on the
antibiofouling membrane in contrast to the control. However, specific oxygen
uptake rate and dehydrogenase activity analyses demonstrated no adverse impacts
on microbial viability of the bulk activated sludge. Bacterial population
analysis using the Illumina Miseq platform added further evidence that the use of
antibiofouling membrane did not exert negative influences on richness, diversity
and structure of the bacterial community. Effluent quality of the test MBR also
exhibited minimal difference from that of the control reactor. The amount of
polysaccharides and proteins in the biofouling layer was also significantly
reduced. Quartz crystal microbalance with dissipation monitoring suggested that
the antibiofouling membrane only allowed organic matter with strong adhesion
properties to attach onto the membrane surfaces. These findings highlight the
potential of the antibiofouling membrane to be used in MBRs for wastewater
treatment and reclamation.
PMID- 28501787
TI - Free chlorine and monochloramine inactivation kinetics of Aspergillus and
Penicillium in drinking water.
AB - Fungi are near-ubiquitous in potable water distribution systems, but the
disinfection kinetics of commonly identified fungi are poorly studied. In the
present study, laboratory scale experiments were conducted to evaluate the
inactivation kinetics of Aspergillus fumigatus, Aspergillus versicolor, and
Penicillium purpurogenum by free chlorine and monochloramine. The observed
inactivation data were then fit to a delayed Chick-Watson model. Based on the
model parameter estimation, the Ct values (integrated product of disinfectant
concentration C and contact time t over defined time intervals) for 99.9%
inactivation of the tested fungal strains ranged from 48.99 mg min/L to 194.7 mg
min/L for free chlorine and from 90.33 mg min/L to 531.3 mg min/L for
monochloramine. Fungal isolates from a drinking water system (Aspergillus
versicolor and Penicillium purpurogenum) were more disinfection resistant than
Aspergillus fumigatus type and clinical isolates. The required 99.9% inactivation
Ct values for the tested fungal strains are higher than E. coli, a commonly
monitored indicator bacteria, and within a similar range for bacteria commonly
identified within water distribution systems, such as Mycobacterium spp. and
Legionella spp.
PMID- 28501788
TI - Dynamic femoral head translations in dysplastic hips.
AB - BACKGROUND: Developmental dysplasia of the hip is an important disease leading to
osteoarthritis. Recently, researchers have focused on hip instability as a
potentially important dynamic factor for osteoarthritis, but the detailed
kinematics of dysplastic hips during weight-bearing gait have not been reported.
The purpose of this research is to contrast femoral translation in contralateral
healthy hips and dysplastic hips during weight-bearing stepping. METHODS: Twelve
dysplastic hips and eight healthy hips were investigated. Hip joint kinematics
were analyzed using 3D-2D model-image registration with dynamic fluoroscopic
images of each hip during a stepping-in-place activity. Femoral translation
relative to the acetabular center was quantified as instability. FINDINGS: Total
femoral head translations were significantly different between dysplastic and
contralateral healthy hips. Mean translation was 1.0mm in dysplastic hips and
0.4mm in contralateral healthy hips during swing-phase, and consisted of inferior
translation during early swing phase with a complementary superior translation
just before foot strike. Total femoral translation was significantly correlated
to several radiographic indices of hip dysplasia. INTERPRETATION: Superior
translations of the femur during the end of swing phase may result in altered
articular contact mechanics, abnormal stresses on the labrum and lost lubricant
sealing. All of these factors may contribute to joint degeneration and
osteoarthritis in dysplastic hips.
PMID- 28501789
TI - Country-specific and individual determinants of dizziness in Europe: results from
the Survey of Health Ageing and Retirement in Europe (SHARE).
AB - OBJECTIVES: Dizziness is one of the most common complaints amongst older persons
and has relevant consequences for functioning. However, the epidemiological
findings on dizziness are scarce and inconsistent and prevalence varies
considerably among existing studies. Hence the objective of this study is to
compare the prevalence of dizziness in persons aged 50 years or older across
several European countries. The specific aim was to identify country- and person
specific determinants associated with a higher risk. STUDY DESIGN: Cross
sectional study. METHODS: Data from the Survey of Health Ageing and Retirement in
Europe project, covering 20 countries were analysed. Micro-data on more than
69,000 persons aged 50+ years and additional macro-data on economic inequality,
climate and urbanisation were included. We applied multilevel models to examine
the impact of country-50 years or older specific determinants as well as
individual characteristics on prevalence of dizziness. RESULTS: We found a total
of 12.4% of the participants in our sample were troubled by dizziness in the last
6 months. Prevalence ranged from 6.5% to 23.4%. In multilevel analysis several
determinants on the country (higher proportion of urban population) and on the
individual level (female gender, living alone, old age, poor education, presence
of comorbidities, depressive symptoms, sensory problems, lack of physical
activities) were identified. CONCLUSIONS: In conclusion dizziness is a common
complaint amongst older Europeans that needs more attention. Further studies
should investigate the prevalence, determinants and management of defined
vestibular and non-vestibular causes of dizziness across Europe.
PMID- 28501791
TI - The jurisprudence of emergency medical care in India: an ethics perspective.
AB - This paper, which is part of a primary interdisciplinary doctoral research work
with a qualitative research design, seeks to understand the ethical principles
that intersect healthcare jurisprudence in litigations where citizens, who have
encountered death or violations in the provision of critical care, have had to
take recourse to the courts to get justice.
PMID- 28501792
TI - Healing ministry and palliative care in Christianity.
AB - Death is inevitable, but that does not mean it can be planned or imposed. It is
an ethical imperative that we attend to the unbearable pain and suffering of
patients with incurable and terminal illnesses. This is where palliative care
plays a vital role. Palliative care has been growing faster in the world of
medicine since its emergence as a specialty in the last decade. Palliative care
helps to reduce physical pain while affirming the aspect of human suffering and
dying as a normal process. The goal of palliative care is to improve the quality
of life both of the patient and the family. Palliative care resonates with the
healing ministry of Christianity that affirms the sanctity and dignity of human
life from the moment of conception to natural death. Christianity is convinced
that patients at the very end of their lives, with all their ailments and
agonies, are still people who have been created in the image and likeness of God.
The human person is always precious, even when marked by age and sickness. This
is one of the basic convictions that motivate Christians to take care of the sick
and the dying. Palliative care is a great opportunity for Christians to manifest
God's unfailing love for the terminally ill and the dying.
PMID- 28501790
TI - Obesity aggravates toxic effect of BPA on spermatogenesis.
AB - Both bisphenol A (BPA) and obesity affect male reproductive system. However,
whether there is an interaction between them remains poorly understood. The aim
of the present study was to evaluate the interaction between BPA exposure and
obesity on semen quality and elucidate the mechanism in humans and animals. We
firstly analyzed the interaction on semen volume, sperm count per ejaculate,
sperm concentration and sperm motility in 357 men, and found that urinary BPA
concentration was significantly correlated with sperm count per ejaculate in
obese men (beta=-34.62; 95% CI: -60.75, -8.48; P=0.01). Then we validated the
interaction using lean and obese mice with administration of BPA. Significant
interactions between BPA exposure and obesity on sperm count and sperm
concentration was observed in mice. Finally, we conducted metabolomics analyses
to identify metabolites related to the interaction. Metabolites related to the
interaction, including capric acid, dodecanoic acid, l-palmitoylcarnitine,
niacinamide, etc., are known to play critical roles in fatty acid oxidation and
tricarboxylic acid cycle indicating increased oxidative stress associated with
male reproductive dysfunction. Thus, our study finds an interaction between BPA
exposure and obesity on sperm count and reveals potential metabolic mechanisms.
It emphasizes the importance to study interactions between endocrine disrupting
chemicals and obesity, and opens avenues for the possible use of animal models in
identifying the interactions.
PMID- 28501793
TI - Ethical issues in death, dying and palliation: the IJME Sixth National Bioethics
Conference.
PMID- 28501794
TI - Cochrane corner: renal denervation for resistant hypertension-a broken promise?
PMID- 28501795
TI - Patient preferences for cardiovascular preventive medication: a systematic
review.
AB - OBJECTIVE: To systematically review current evidence regarding the minimum
acceptable risk reduction of a cardiovascular event that patients feel would
justify daily intake of a preventive medication. METHODS: We used the Web of
Science to track the forward and backward citations of a set of five key articles
until 15 November 2016. Studies were eligible if they quantitatively assessed the
minimum acceptable benefit-in absolute values-of a cardiovascular disease
preventive medication among a sample of the general population and required
participants to choose if they would consider taking the medication. RESULTS: Of
341 studies screened, we included 22, involving a total of 17 751 participants: 6
studied prolongation of life (POL), 12 studied absolute risk reduction (ARR) and
14 studied number needed to treat (NNT) as measures of risk reduction
communicated to the patients. In studies framed using POL, 39%-54% (average: 48%)
of participants would consider taking a medication if it prolonged life by <8
months and 56%-73% (average: 64%) if it prolonged life by >=8 months. In studies
framed using ARR, 42%-72% (average: 54%) of participants would consider taking a
medication that reduces their 5-year cardiovascular disease (CVD) risk by <3% and
50%-89% (average: 77%) would consider taking a medication that reduces their 5
year CVD risk by >=3%. In studies framed using 5-year NNT, 31%-81% (average: 60%)
of participants would consider taking a medication with an NNT of >30 and 46%-87%
(average: 71%) with an NNT of <=30. CONCLUSIONS: Many patients require a
substantial risk reduction before they consider taking a daily medication
worthwhile, even when the medication is described as being side effect free and
costless.
PMID- 28501796
TI - Nitric oxide synthase inhibition restores orthostatic tolerance in young
vasovagal syncope patients.
AB - OBJECTIVE: Syncope is sudden transient loss of consciousness and postural tone
with spontaneous recovery; the most common form is vasovagal syncope (VVS). We
previously demonstrated impaired post-synaptic adrenergic responsiveness in young
VVS patients was reversed by blocking nitric oxide synthase (NOS). We
hypothesised that nitric oxide may account for reduced orthostatic tolerance in
young recurrent VVS patients. METHODS: We recorded haemodynamics in supine VVS
and healthy volunteers (aged 15-27 years), challenged with graded lower body
negative pressure (LBNP) (-15, -30, -45 mm Hg each for 5 min, then -60 mm Hg for
a maximum of 50 min) with and without NOS inhibitor NG-monomethyl-L-arginine
acetate (L-NMMA). Saline plus phenylephrine (Saline+PE) was used as volume and
pressor control for L-NMMA. RESULTS: Controls endured 25.9+/-4.0 min of LBNP
during Saline+PE compared with 11.6+/-1.4 min for fainters (p<0.001). After L
NMMA, control subjects endured 24.8+/-3.2 min compared with 22.6+/-1.6 min for
fainters. Mean arterial pressure decreased more in VVS patients during LBNP with
Saline+PE (p<0.001) which was reversed by L-NMMA; cardiac output decreased
similarly in controls and VVS patients and was unaffected by L-NMMA. Total
peripheral resistance increased for controls but decreased for VVS during
Saline+PE (p<0.001) but was similar following L-NMMA. Splanchnic vascular
resistance increased during LBNP in controls, but decreased in VVS patients
following Saline+PE which L-NMMA restored. CONCLUSIONS: We conclude that arterial
vasoconstriction is impaired in young VVS patients, which is corrected by NOS
inhibition. The data suggest that both pre- and post-synaptic arterial
vasoconstriction may be affected by nitric oxide.
PMID- 28501797
TI - Predictors of procedural complications in adult Fontan patients undergoing non
cardiac procedures.
AB - OBJECTIVE: Limited data exist regarding the outcomes of non-cardiac procedures
(NCPs) in adult patients after Fontan operations (Fontan patients). METHODS: To
compare procedural outcomes after NCPs in Fontan patients with outcomes for two
matched control groups: patients with repaired congenital heart disease and
biventricular circulation (CHD-BiV) and patients with no heart disease (NHD). We
defined cyanosis as oxygen saturation <90% and procedural hypoxia as saturation
<80% or a decrease in saturation >10% from baseline. RESULTS: There were 538 NCPs
in 154 Fontan patients (mean age, 30 years) performed in 1990-2015. Sedation and
anaesthesia types were monitored anaesthesia care (256,48%), general anaesthesia
(51,9%), minimal sedation (105,20%), local anaesthesia (75,14%) and regional
anaesthesia (51,9%). Ninety-three complications occurred in 79 procedures (15%)
and included arrhythmia requiring intervention (9), hypotension (14), bradycardia
(8), hypoxia (38), heart failure requiring intravenous diuretics (2), acute
kidney injury (3), bleeding requiring blood transfusion (1), unplanned procedures
for dialysis catheter placement (2), readmission (2), unplanned hospitalisation
for hypoxia (8) and unplanned transfer to intensive care unit (1). Baseline
cyanosis was the only multivariable risk factor for complications (HR, 1.87 (95%
CI 1.14 to 3.67), p=0.04). Procedural complications were more common in the
Fontan group (18%) than in the CHD-BiV (5%) and NHD groups (1.4%) (p=0.001).
CONCLUSIONS: Complications after NCPs were more common in Fontan patients, and
baseline cyanosis was a risk factor for complications. All-cause mortality was
low and may be related to the multidisciplinary care approach used for Fontan
patients at our centre.
PMID- 28501798
TI - Dose-time-response association between occupational asbestos exposure and pleural
mesothelioma.
AB - OBJECTIVES: Early occupational exposure to asbestos has been shown to be
associated with an increased risk of pleural mesothelioma (PM), which suggests
that the timing of exposure might play a role in the dose-response relationship.
However, none studies has evaluated the relative impact of increasing the annual
intensity of occupational exposure to asbestos at each time of the whole exposure
history. Yet such evaluation would allow the comparison of the risks of PM
associated with different longitudinal profiles of occupational exposure to
asbestos. Our objective was to estimate the time-dependent relative impact of
asbestos exposure intensity over the whole occupational history and to compare
the resulting estimated risks of PM associated with different profiles of
exposure, using data from a large French case-control study. METHODS: This study
included 1196 male cases recruited in 1987-2006 and 2369 matched controls on
birth year. Occupational exposure to asbestos was assessed using a job exposure
matrix and represented in logistic regression models using a flexible weighted
cumulative index of exposure. RESULTS: Due to much stronger weights of early
doses of asbestos exposure, subjects who accumulated 20 fibres/mL over their
entire job history with high doses during the first years and low doses
thereafter were at higher risk of PM than those who accumulated most of the doses
later (OR=2.37 (95% CI 2.01 to 2.87)). CONCLUSION: This study provides new
insights on the dose-time-response relationship between occupational asbestos and
PM and illustrates the importance of considering timing of exposure in its
association with cancer risk.
PMID- 28501800
TI - Ustekinumab inhibits Th1 and Th17 polarisation in a patient with giant cell
arteritis.
PMID- 28501799
TI - High maternal expression of SIGLEC1 on monocytes as a surrogate marker of a type
I interferon signature is a risk factor for the development of autoimmune
congenital heart block.
AB - OBJECTIVES: Autoimmune congenital heart block (CHB) is associated with placental
transcytosis of maternal autoantibodies directed against Ro/SS-A and La/SS-B.
However, only about 2% of children born to mothers with the respective antibodies
are affected, indicating that further risk factors exist, which are not yet fully
understood. In this study, we investigated whether a maternal type I interferon
(IFN) signature represents a risk factor for the development of CHB. METHODS:
Blood samples, clinical data and serological parameters from 9 women with CHB
pregnancies, 14 pregnant women with antibodies against Ro/SS-A but without a CHB
complication and another 30 healthy pregnant women as controls were studied.
SIGLEC1 expression was measured by flow cytometry and was correlated to plasma
IFN-alpha levels measured by ELISA, and IFN-gamma-induced protein 10 (IP-10)
levels measured by Bio-Plex technique. RESULTS: Mothers of affected children had
a significantly higher expression of SIGLEC1 (p=0.0034) and IFN-alpha (p=0.014),
but not of IP-10 (p=0.14, all MWU) compared to mothers of unaffected children.
SIGLEC1 and IFN-alpha expression were reduced by hydroxychloroquine and oral
glucocorticoids. CONCLUSIONS: High expression of SIGLEC1 in pregnant women with
autoantibodies against Ro/SS-A indicates an enhanced risk for CHB development,
and these women may benefit especially from IFN-alpha directed therapy, for
example with hydroxychloroquine.
PMID- 28501801
TI - A rare coding allele in IFIH1 is protective for psoriatic arthritis.
AB - OBJECTIVES: Psoriatic arthritis (PsA) is an inflammatory arthritis associated
with psoriasis. While many common risk alleles have been reported for association
with PsA as well as psoriasis, few rare coding alleles have yet been identified.
METHODS: To identify rare coding variation associated with PsA risk or
protection, we genotyped 41 267 variants with the exome chip and investigated
association within an initial cohort of 1980 PsA cases and 5913 controls.
Genotype data for an independent cohort of 2234 PsA cases and 5708 controls was
also made available, allowing for a meta-analysis to be performed with the
discovery dataset. RESULTS: We identified an association with the rare variant
rs35667974 (p=2.39x10-6, OR=0.47), encoding an Ile923Val amino acid change in the
IFIH1 gene protein product. The association was reproduced in our independent
cohort, which reached a high level of significance on meta-analysis with the
discovery and replication datasets (p=4.67x10-10). We identified a strong
association with IFIH1 when performing multiple-variant analysis (p=6.77x10-6),
and found evidence of independent effects between the rare allele and the common
PsA variant at the same locus. CONCLUSION: For the first time, we report a rare
coding allele in IFIH1 to be protective for PsA. This rare allele has also been
identified to have the same direction of effect on type I diabetes and psoriasis.
While this association further supports existing evidence for IFIH1 as a causal
gene for PsA, mechanistic studies will need to be pursued to confirm that IFIH1
is indeed causal.
PMID- 28501803
TI - Among opioid-naive patients receiving opioids, more intensive opioid prescribing
in the first month is associated with transition to long-term opioid use.
PMID- 28501802
TI - Stability of Proteins in Dried Blood Spot Biobanks.
AB - An important motivation for the construction of biobanks is to discover
biomarkers that identify diseases at early, potentially curable stages. This will
require biobanks from large numbers of individuals, preferably sampled
repeatedly, where the samples are collected and stored under conditions that
preserve potential biomarkers. Dried blood samples are attractive for biobanking
because of the ease and low cost of collection and storage. Here we have
investigated their suitability for protein measurements. Ninety-two proteins with
relevance for oncology were analyzed using multiplex proximity extension assays
(PEA) in dried blood spots collected on paper and stored for up to 30 years at
either +4 degrees C or -24 degrees C.Our main findings were that (1) the act of
drying only slightly influenced detection of blood proteins (average correlation
of 0.970), and in a reproducible manner (correlation of 0.999), (2) detection of
some proteins was not significantly affected by storage over the full range of
three decades (34 and 76% of the analyzed proteins at +4 degrees C and -24
degrees C, respectively), whereas levels of others decreased slowly during
storage with half-lives in the range of 10 to 50 years, and (3) detectability of
proteins was less affected in dried samples stored at -24 degrees C compared
with at +4 degrees C, as the median protein abundance had decreased to 80 and
93% of starting levels after 10 years of storage at +4 degrees C or -24 degrees
C, respectively. The results of our study are encouraging as they suggest an
inexpensive means to collect large numbers of blood samples, even by the donors
themselves, and to transport, and store biobanked samples as spots of whole blood
dried on paper. Combined with emerging means to measure hundreds or thousands of
protein, such biobanks could prove of great medical value by greatly enhancing
discovery as well as routine analysis of blood biomarkers.
PMID- 28501805
TI - Neurological tests improve after Olympic-style boxing bouts: a pretournament and
post-tournament study in the 2016 Women's World Boxing Championships.
AB - AIM: To prospectively examine the neurocognitive, postural, dual-task and visual
abilities of female Olympic-style boxers before and after participation in a
tournament. METHODS: Sixty-one females completed the modified Balance Error
Scoring System (mBESS), King-Devick test and 3 m timed-up-and-go test in single
task and dual-task conditions. A subset (n=31) completed the CogState
computerised neurocognitive test. Initial testing was completed prior to the 2016
Women's World Boxing Championships; each participant repeated the testing
protocol within a day of elimination. No participant sustained a concussion.
Pretournament and post-tournament performance variables were compared using
paired t-tests or Wilcoxon signed-rank tests. RESULTS: Participants completed a
mean of 7.5+/-4.5 rounds of Olympic-style boxing over 2-8 days. Post-tournament
scores were significantly lower than pretournament scores for total mBESS (2.2+/
1.9 errors vs 5.5+/-2.9 errors, p<0.001, d=1.23) and King-Devick time (14.2+/-3.9
s vs 18.0+/-8.3 s, p=0.002, d=0.53). Processing speed was significantly faster
after the boxing tournament (maze chase task: 1.39+/-0.34 correct moves/second vs
1.17+/-0.44 correct moves/second, p=0.001, d=0.58). No significant changes across
time were detected for the other obtained outcome variables. CONCLUSIONS: Female
boxers demonstrated either improvement or no significant changes in test
performance after competing in an Olympic-style boxing tournament, relative to
pretournament performance. As many of the test tasks were novel for the boxers,
practice effects may have contributed to improved performance. When there is a
short time frame between assessments, clinicians should be aware of potential
practice effects when using ringside neurological tests.
PMID- 28501807
TI - Unilateral papilloedema.
PMID- 28501808
TI - Bureaucracy, trust and time: recruitment in a low-risk study of paediatric
protocols forchildren who miss medicalappointments.
PMID- 28501804
TI - Exercise and other non-pharmaceutical interventions for cancer-related fatigue in
patients during or after cancer treatment: a systematic review incorporating an
indirect-comparisons meta-analysis.
AB - AIM: To assess the relative effects of different types of exercise and other non
pharmaceutical interventions on cancer-related fatigue (CRF) in patients during
and after cancer treatment. DESIGN: Systematic review and indirect-comparisons
meta-analysis. DATA SOURCES: Articles were searched in PubMed, Cochrane CENTRAL
and published meta-analyses. ELIGIBILITY CRITERIA FOR SELECTING STUDIES:
Randomised studies published up to January 2017 evaluating different types of
exercise or other non-pharmaceutical interventions to reduce CRF in any cancer
type during or after treatment. STUDY APPRAISAL AND SYNTHESIS: Risk of bias
assessment with PEDro criteria and random effects Bayesian network meta-analysis.
RESULTS: We included 245 studies. Comparing the treatments with usual care during
cancer treatment, relaxation exercise was the highest ranked intervention with a
standardisedmean difference (SMD) of -0.77 (95% Credible Interval (CrI) -1.22 to
0.31), while massage (-0.78; -1.55 to -0.01), cognitive-behavioural therapy
combined with physical activity (combined CBT, -0.72; -1.34 to -0.09), combined
aerobic and resistance training (-0.67; -1.01 to -0.34), resistance training (
0.53; -1.02 to -0.03), aerobic (-0.53; -0.80 to -0.26) and yoga (-0.51; -1.01 to
0.00) all had moderate-to-large SMDs. After cancer treatment, yoga showed the
highest effect (-0.68; -0.93 to -0.43). Combined aerobic and resistance training
(-0.50; -0.66 to -0.34), combined CBT (-0.45; -0.70 to -0.21), Tai-Chi (-0.45;
0.84 to -0.06), CBT (-0.42; -0.58 to -0.25), resistance training (-0.35; -0.62 to
-0.08) and aerobic (-0.33; -0.51 to -0.16) showed all small-to-moderate SMDs.
CONCLUSIONS: Patients can choose among different effective types of exercise and
non-pharmaceutical interventions to reduce CRF.
PMID- 28501806
TI - Exercise in type 2 diabetes: genetic, metabolic and neuromuscular adaptations. A
review of the evidence.
AB - The biological responses to exercise training are complex, as almost all organs
and systems are involved in interactions that result in a plethora of adaptations
at the genetic, metabolic and neuromuscular levels.To provide the general
practitioner and the sports medicine professionals with a basic understanding of
the genetic, metabolic and neuromuscular adaptations at a cellular level that
occur with aerobic and resistance exercise in subjects with type 2 diabetes.For
each of the three domains (genetic, metabolic and neuromuscular), the results of
the major systematic reviews and original research published in relevant
journals, indexed in PubMed, were selected. Owing to limitations of space, we
focused primarily on the role of skeletal muscle, given its pivotal role in
mediating adaptations at all levels.Generally, training-induced adaptations in
skeletal muscle are seen as changes in contractile proteins, mitochondrial
function, metabolic regulation, intracellular signalling, transcriptional
responses and neuromuscular modifications. The main adaptation with clinical
relevance would include an improved oxidative capacity derived from aerobic
training, in addition to neuromuscular remodelling derived from resistance
training. Both training modalities improve insulin sensitivity and reduce
cardiovascular risk.Taken together, the modifications that occur at the genetic,
metabolic and neuromuscular levels, work correlatively to optimise substrate
delivery, mitochondrial respiratory capacity and contractile function during
exercise.
PMID- 28501809
TI - Non-specific effects of vaccines: plausible and potentially important, but
implications uncertain.
AB - Non-specific effects (NSE) or heterologous effects of vaccines are proposed to
explain observations in some studies that certain vaccines have an impact beyond
the direct protection against infection with the specific pathogen for which the
vaccines were designed. The importance and implications of such effects remain
controversial. There are several known immunological mechanisms which could lead
to NSE, since it is widely recognised that the generation of specific immunity is
initiated by non-specific innate immune mechanisms that may also have wider
effects on adaptive immune function. However, there are no published studies that
demonstrate a mechanistic link between such immunological phenomena and
clinically relevant NSE in humans. While it is highly plausible that some
vaccines do have NSE, their magnitude and duration, and thus importance, remain
uncertain. Although the WHO recently concluded that current evidence does not
justify changes to immunisation policy, further studies of sufficient size and
quality are needed to assess the importance of NSE for all-cause mortality. This
could provide insights into vaccine immunobiology with important implications for
infant health and survival.
PMID- 28501810
TI - Alveolar rhabdomyosarcoma in a 6-month-old boy.
PMID- 28501811
TI - Haemodynamic analysis for recanalisation of intracranial aneurysms after
endovascular treatment: an observational registry study in China.
AB - INTRODUCTION: Recanalisation of intracranial aneurysms following endovascular
treatment is a major issue. Many factors, including aneurysm morphology, the
method of treatment, and haemodynamics, are considered to be associated with
recanalisation. However, the underlying haemodynamic mechanisms are not
completely understood. METHODS AND ANALYSIS: This is a prospective,
observational, registry study for patients with intracranial aneurysms who are
treated endovascularly. It will enrol 200 eligible patients. Data on
morphological, haemodynamic, and treatment factors will be collected
prospectively. The advanced virtual stenting technique and porous media method
will be used in haemodynamic simulations. The clinical and angiographic outcomes
at 6 months will be measured and analysed. This observational study will
determine the haemodynamic factors that affect the recanalisation of aneurysms.
ETHICS AND DISSEMINATION: Both the study protocol and written informed consent
were reviewed and approved by the Institutional Review Board of Beijing Tiantan
Hospital (KY2016-023-01). The results of study will be disseminated in
professional printed media. TRIAL REGISTRATION NUMBER: NCT02812108; Pre-results.
PMID- 28501812
TI - Integrating culturally informed approaches into the physiotherapy assessment and
treatment of chronic pain: protocol for a pilot randomised controlled trial.
AB - INTRODUCTION: There is strong evidence that biopsychosocial approaches are
efficacious in the management of chronic pain. However, implementation of these
approaches in clinical practice is known not to account for the beliefs and
values of culturally and linguistically diverse (CALD) patients. This limitation
in translation of research contributes to the disparities in outcomes for CALD
patients with chronic pain adding to the socioeconomic burden of this prevalent
condition. Cultural adaptation of chronic pain assessment and management is
urgently required. Thus, the aim of this pilot randomised controlled trial (RCT)
is to determine the feasibility, participant acceptance with and clinical
effectiveness of a culturally adapted physiotherapy assessment and treatment
approach when contrasted with 'usual evidence based physiotherapy care' for three
CALD communities. METHODS AND ANALYSIS: Using a participant-blinded and assessor
blinded randomised controlled pilot design, patients with chronic pain who self
identify as Assyrian, Mandaean or Vietnamese will be randomised to either
'culturally adapted physiotherapy assessment and treatment' or 'evidence informed
usual physiotherapy care'. We will recruit 16 participants from each
ethnocultural community that will give a total of 24 participants in each
treatment arm. Both groups will receive physiotherapy treatment for up to 10
sessions over 3 months. Outcomes including feasibility data, acceptance with the
culturally adapted intervention, functional and pain-related measures will be
collected at baseline and 3 months by a blinded assessor. Analysis will be
descriptive for feasibility outcomes, while measures for clinical effectiveness
will be explored using independent samples t-tests and repeated measures analysis
of variance. This analysis will inform sample size estimates while also allowing
for identification of revisions in the protocol or intervention prior to a larger
scale RCT. ETHICS AND DISSEMINATION: This trial has full ethical approval
(HREC/16/LPOOL/194). The results from this pilot RCT will be presented at
scientific meetings and published in peer-reviewed journals. TRIAL REGISTRATION
NUMBER: ACTRN12616000857404.
PMID- 28501813
TI - The relationship between job satisfaction, work stress, work-family conflict, and
turnover intention among physicians in Guangdong, China: a cross-sectional study.
AB - OBJECTIVE: To investigate the relationship between job satisfaction, work stress,
work-family conflict and turnover intention, and explore factors associated with
turnover intention, among physicians in Guangdong Province, China. METHODS: From
August to October 2013, physicians completed questionnaires and scales with
regard to their job satisfaction, work stress, work-family conflict, and turnover
intention. Binary logistic regression and structural equation modelling (SEM)
were used in data analysis. RESULTS: A total of 3963 physicians were approached,
with 3563 completing the questionnaire. The mean score of the overall perception
of turnover intention of physicians who worked in Guangdong was 2.71 on a scale
ranging from 1 to 6. Hours worked per week, working in an urban/rural area, type
of institution, and age significantly impacted on turnover intention. Turnover
intention was directly and negatively related to job satisfaction, and it was
directly, indirectly and positively related to work stress and work-family
conflict. CONCLUSION: Job satisfaction, work stress, work-family conflict, hours
worked per week, working in an urban/rural area, types of institution and age are
influencing factors of turnover intention. Reducing working hours, raising
salary, providing more opportunities for career development and training,
supporting and encouraging physicians by senior managers could potentially
contribute to the reduction in turnover intention.
PMID- 28501814
TI - A scoping review protocol on social participation of indigenous elders,
intergenerational solidarity and their influence on individual and community
wellness.
AB - INTRODUCTION: Indigenous elders have traditionally played an important role in
maintaining social cohesion within their communities. Today, part of this role
has been taken over by government social and healthcare services, but they are
having limited success in addressing social challenges. Increasing elders' social
participation and intergenerational solidarity might foster community development
and benefit young people, families, communities and the elders themselves.
However, knowledge of the contribution of elders' social participation and
intergenerational solidarity to wellness is scattered and needs to be
synthesised. This protocol presents a scoping review on the social participation
of indigenous elders, intergenerational solidarity and their influence on
individual and community wellness. METHODS AND ANALYSIS: This scoping review
protocol is based on an innovative methodological framework designed to gather
information from the scientific and grey literature and from indigenous sources.
It was developed by an interdisciplinary team including indigenous
scholars/researchers, knowledge users and key informants. In addition to
searching information databases in fields such as public health and indigenous
studies, an advisory committee will ensure that information is gathered from grey
literature and indigenous sources. ETHICS: The protocol was approved by the
Ethics Review Board of the Universite du Quebec en Abitibi-Temiscamingue and the
First Nations of Quebec and Labrador Health and Social Services Commission.
DISCUSSION: The comprehensive synthesis of the scientific and grey literature and
indigenous sources proposed in this protocol will not only raise awareness within
indigenous communities and among healthcare professionals and community
organisations, but will also enable decision-makers to better meet the needs of
indigenous people. CONCLUSION: The innovative methodological framework proposed
in this scoping review protocol will yield richer information on the contribution
of elders to community wellness. This work is an essential preliminary step
towards developing research involving indigenous communities, drawing on the
social participation of elders and intergenerational solidarity.
PMID- 28501815
TI - Can the prehospital National Early Warning Score identify patients most at risk
from subsequent deterioration?
AB - INTRODUCTION: The National Early Warning Score (NEWS) aids the early recognition
of those at risk of becoming critically ill. NEWS has been recommended for use by
ambulance services, but very little work has been undertaken to date to determine
its suitability. This paper examines whether a prehospital NEWS derived from
ambulance service clinical observations is associated with the hospital ED
disposition. METHODS: Prehospital NEWS was retrospectively calculated from the
ambulance service clinical records of 287 patients who were treated by the
ambulance service and transported to hospital. In this cohort study, derived NEWS
scores were compared with ED disposition data and patients were categorised into
the following groups depending on their outcome: discharged from ED, admitted to
a ward, admitted to intensive therapy unit (ITU) or died. RESULTS: Prehospital
NEWS-based ambulance service clinical observations were significantly associated
with discharge disposition groups (p<0.001), with scores escalating in line with
increasing severity of outcome. Patients who died or were admitted to ITU had
higher scores than those admitted to a ward or discharged from ED (mean NEWS 7.2
and 7.5 vs 2.6 and 1.7, respectively), and in turn those who were admitted to a
ward had higher pre-hospital NEWS than those who were discharged (2.6 vs 1.7).
CONCLUSION: Our findings suggest that the NEWS could successfully be used by
ambulance services to identify patients most at risk from subsequent
deterioration. The implementation of this early warning system has the potential
to support ambulance clinician decision making, providing an additional tool to
identify and appropriately escalate care for acutely unwell patients.
PMID- 28501817
TI - Putting the Wnt up colon cancer.
PMID- 28501816
TI - Emergency medicine pharmacists on an international scale.
PMID- 28501819
TI - Six issues in muscle disease.
PMID- 28501820
TI - IgM MGUS and Waldenstrom-associated anti-MAG neuropathies display similar
response to rituximab therapy.
PMID- 28501823
TI - Cerebellar atrophy in neurodegeneration-a meta-analysis.
AB - INTRODUCTION: The cerebellum has strong cortical and subcortical connectivity,
but is rarely taken into account for clinical diagnosis in many neurodegenerative
conditions, particularly in the absence of clinical ataxia. The current meta
analysis aims to assess patterns of cerebellar grey matter atrophy in seven
neurodegenerative conditions (Alzheimer's disease (AD), Parkinson's disease (PD)
and Huntington's disease (HD), frontotemporal dementia (FTD), amyotrophic lateral
sclerosis (ALS), multiple system atrophy (MSA), progressive supranuclear palsy
(MSP)). METHODS: We carried out a systematic search in PubMed (any date: 14 July
2016) and a hand search of references from pertinent articles according to the
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
guidelines. The authors were contacted to provide missing coordinate data. Peer
reviewed studies with direct comparison of patient and control groups, and
availability of coordinate data of grey matter cerebellar atrophy in patients
were included. These coordinates were used in an anatomical likelihood estimation
meta-analysis. RESULTS: Across 54 studies, clusters of cerebellar atrophy were
found for AD, ALS, FTD, MSA, and PSP. Atrophy patterns were largely disease
specific, with overlap in certain areas of the cerebellar hemisphere, which
showed marked atrophy in AD, ALS, FTD and PSP (Crus I/II), and MSA and PSP
(lobules I-IV), respectively. Atrophy colocated with cerebellar areas implicated
for motor (PSP, MSA) or cognitive symptoms (FTD, ALS, PSP) in the diseases.
DISCUSSION: Our findings suggest that cerebellar changes are largely disease
specific and correspond to cortical or subcortical changes in neurodegenerative
conditions. High clinical variability in PD and HD samples may explain the
absence of findings for consistent grey matter loss across studies. Our results
have clinical implications for diagnosis and cerebellar neuroimaging referencing
approaches.
PMID- 28501822
TI - Structural MRI correlates of amyotrophic lateral sclerosis progression.
AB - PURPOSE: Amyotrophic lateral sclerosis (ALS) presents with varying degrees of
brain degeneration that can extend beyond the corticospinal tract (CST).
Furthermore, the clinical course and progression of ALS varies widely. Brain
degeneration detected using structural MRI could reflect disease progression.
SUBJECTS AND METHODS: On study registration, 3-Tesla volumetric MRI and diffusion
tensor imaging scans were obtained at baseline in 38 healthy controls and 67
patients with sporadic ALS. Patients had Amyotrophic Lateral Sclerosis Functional
Rating Scale-Revised (ALSFRS-R) scores of >=36 and did not have the chromosome 9,
open reading frame 72 repeat expansion. Six months later, changes in ALSFRS-R
(DeltaALSFRS-R) scores were calculated and patients were grouped into three
categories, namely, patients with slow progression with DeltaALSFRS-R scores <=3
(n=19), intermediate progression with DeltaALSFRS-R scores =4, 5 and 6 (n=36) and
rapid progression with DeltaALSFRS-R scores >=7 (n=12). We analysed voxel-based
morphometry and tract-based spatial statistics among these subgroups and
controls. RESULTS: In comparison with controls, patients with ALS showed grey
matter atrophy and decreased fractional anisotropy beyond the motor cortex and
CST, especially in the frontotemporal lobes and basal ganglia. Moreover, the
degree of change was highly proportional to DeltaALSFRS-R at the 6-month
assessment. CONCLUSION: A more rapid disease progression and poorer functional
decline were associated with greater involvement of the extra-motor cortex and
basal ganglia, suggesting that the spatial extent of brain involvement can be an
indicator of the progression in ALS.
PMID- 28501821
TI - Genetic and clinical characteristics of NEFL-related Charcot-Marie-Tooth disease.
AB - OBJECTIVES: To analyse and describe the clinical and genetic spectrum of Charcot
Marie-Tooth disease (CMT) caused by mutations in the neurofilament light
polypeptide gene (NEFL). METHODS: Combined analysis of newly identified patients
with NEFL-related CMT and all previously reported cases from the literature.
RESULTS: Five new unrelated patients with CMT carrying the NEFL mutations P8R and
N98S and the novel variant L311P were identified. Combined data from these cases
and 62 kindreds from the literature revealed four common mutations (P8R, P22S,
N98S and E396K) and three mutational hotspots accounting for 37 (55%) and 50
(75%) kindreds, respectively. Eight patients had de novo mutations. Loss of large
myelinated fibres was a uniform feature in a total of 21 sural nerve biopsies and
'onion bulb' formations and/or thin myelin sheaths were observed in 14 (67%) of
them. The neurophysiological phenotype was broad but most patients with E90K and
N98S had upper limb motor conduction velocities <38 m/s. Age of onset was <=3
years in 25 cases. Pyramidal tract signs were described in 13 patients and 7
patients were initially diagnosed with or tested for inherited ataxia. Patients
with E90K and N98S frequently presented before age 3 years and developed hearing
loss or other neurological features including ataxia and/or cerebellar atrophy on
brain MRI. CONCLUSIONS: NEFL-related CMT is clinically and genetically
heterogeneous. Based on this study, however, we propose mutational hotspots and
relevant clinical-genetic associations that may be helpful in the evaluation of
NEFL sequence variants and the differential diagnosis with other forms of CMT.
PMID- 28501825
TI - Maternal bradycardia occurring prior to onset of HELLP syndrome in a woman with
pre-eclampsia.
AB - A 36-year-old nulliparous woman developed pre-eclampsia at gestational week (GW)
28-6/7 Cardiac status was checked regularly. Heart rate of 93 beats per minute
(bpm) with left atrial diameter (LAD) of 35 mm, left ventricular hypertrophy and
inferior vena cava diameter (IVCD) of 8 mm at GW 32-0/7 decreased to 48 bpm with
an expanded IVCD to 25 mm, dilated left atrium (LAD to 39 mm), increased
pulmonary arterial pressure, increased systemic vascular resistance (approximate
3000 dyn s/cm5) and biphasic intrarenal venous flow pattern 3.5 hours prior to
childbirth at GW 32-3/7 Epigastralgia, tachycardia (160 bpm) and marked
hypertension (201/111 mm Hg) occurring 2 hours after echocardiography
necessitated caesarean section, with subsequent development of HELLP syndrome.
Acute fluid shift from the splanchnic vasculature to central vasculature may have
occurred causing HELLP syndrome as a result from vasospasm associated with
sympathetic hyperactivity. The cause of bradycardia prior to tachycardia remains
unclear.
PMID- 28501824
TI - The vanishing duodenal polyp: mesenteric invagination presenting as duodenal
pseudopolyp.
AB - Duodenal polypoid masses are an uncommon finding mainly diagnosed incidentally at
endoscopy or surgery. We report a 39-year-old female patient with symptoms of
intermittent stabbing pain in the upper right abdominal quadrant and an iron
deficiency anaemia, without complaints of weight loss, haematemesis or melaena. A
duodenal polyp and acute duodenitis have been described during endoscopic
examinations and CT and ultrasound. Surgical excision of the polyp was advised.
Intraoperatively, an elongated duodenum was remarkable; however, at duodenotomy,
no polyp was found, nor during intraoperative endoscopy. Looking back at the
endoscopy and imaging results, it was noted that the polyp varied in size and
location. It was therefore concluded that we dealt with the pseudopolyp
phenomenon, caused by invagination of the duodenal wall and its mesentery into
the duodenum, presenting as a lipomatous pseudopolyp. Telescopic invagination of
the duodenal wall was facilitated by the elongated hypermobile duodenum.
PMID- 28501826
TI - Urothelial papilloma: a rare cause of gross haematuria in childhood.
AB - Bladder urothelial papilloma is extremely rare in the paediatric population. It
usually presents as painless gross haematuria and its diagnosis implies a high
index of suspicion as other causes of haematuria predominate in this age range.
We describe a 9-year-old boy with two episodes of gross haematuria occurring 1
year apart with spontaneous resolution after 2 days. Bladder ultrasound revealed
an endovesical papillary lesion of 24*24 mm suggestive of bladder tumour. The
diagnosis was confirmed by histopathological examination of the specimen obtained
by cystoscopy with transurethral resection. After 3 years of follow-up with
ultrasound and cystoscopy, there are no signs of recurrence. Due to the low
prevalence of urothelial papilloma, paediatric guidelines for appropriate
management and follow-up are unavailable, making this a challenging entity.
PMID- 28501827
TI - A confirmed case of sugammadex-induced anaphylaxis in a UK hospital.
AB - We report the first published case of confirmed anaphylaxis to sugammadex in a UK
hospital. The patient was given a bolus of sugammadex at the end of surgery. Four
minutes later, he developed hypotension and a widespread erythematous rash.
Multiple epinephrine boluses were administered and a continuous intravenous
infusion of epinephrine commenced. The patient later reported auditory awareness,
which occurred while the diagnosis of anaphylaxis was being made and initial
treatment initiated. Serial serum tryptase levels were consistent with a type I
hypersensitivity reaction. Skin prick and intradermal testing were performed 6
months later confirming allergy to sugammadex. This case restates the potential
for hypersensitivity reactions to develop following the administration of
sugammadex and makes clinicians aware that such reactions may require prolonged
treatment with intravenous infusions of epinephrine. Finally, this case
highlights the importance of maintaining or re-establishing anaesthesia while
managing the emergent situation in order to avoid unintentional awareness.
PMID- 28501829
TI - Genetic causes of optic nerve hypoplasia.
AB - Optic nerve hypoplasia (ONH) is the most common congenital optic nerve anomaly
and a leading cause of blindness in the USA. Although most cases of ONH occur as
isolated cases within their respective families, the advancement in molecular
diagnostic technology has made us realise that a substantial fraction of cases
has identifiable genetic causes, typically de novo mutations. An increasing
number of genes has been reported, mutations of which can cause ONH. Many of the
genes involved serve as transcription factors, participating in an intricate
multistep process critical to eye development and neurogenesis in the neural
retina. This review will discuss the respective genes and mutations, human
phenotypes, and animal models that have been created to gain a deeper
understanding of the disorders. The identification of the underlying gene and
mutation provides an important step in diagnosis, medical care and counselling
for the affected individuals and their families. We envision that future research
will lead to further disease gene identification, but will also teach us about
gene-gene and gene-environment interactions relevant to optic nerve development.
How much of the functional impairment of the various forms of ONH is a reflection
of altered morphogenesis versus neuronal homeostasis will determine the prospect
of therapeutic intervention, with the ultimate goal of improving the quality of
life of the individuals affected with ONH.
PMID- 28501828
TI - Vedolizumab: a novel medical intervention in the treatment of primary sclerosing
cholangitis.
PMID- 28501830
TI - Views of Japanese medical students on the work-life balance of female physicians.
AB - Objectives: To survey medical students on their ideas of future work-life balance
and discuss topics for next-generation medical education. Methods: First-year
(n=372, 34.9% female) and sixth-year medical students (n=311, 44.1% female)
responded to a questionnaire on future self, marriage and childcare, and gender
differences at the workplace. Responses were compared between academic years and
gender. Responses were evaluated by gender and academic year using the Mann
Whitney U test. Significance was set at p<0.01. Results: The first-year and
sixth-year students, regardless of gender, had different views on gender-related
favorable treatment at workplaces {U=13464, p=0.000 (first-year), U=10407,
p=0.000 (sixth-year)}. A greater percentage of female students would choose
career options based on the possibility of marriage and childbirth {U=10689,
p=0.000 (first-year), U=10930, p=0.000 (sixth-year)}. Among first-year students,
a greater percentage of female students expected to work part-time. Also among
first-year students, greater percentages of female students expected to work part
time or leave their jobs temporarily while raising their children. Compared with
first-year male students, first-year female students expected to undertake larger
portions of the childcare and housework burden than their partners. However,
gender differences in work-life balance and childcare leave vanished in the sixth
year students. Conclusions: Female medical students accepted childcare and
housework burdens as inevitable; the work environment they choose might affect
their career development. While support from male partners and institutions must
be increased, voluntary actions and change in mentality of female students need
to be promoted through medical education to prevent them from waiting passively
for the situation to change.
PMID- 28501832
TI - [Features of autonomic dysfunction in myofascial pain syndromes cervicobrachial
localization].
AB - INTRODUCTION: The relevance of this study is due to the prevalence of autonomic
disorders and musculoskeletal pain, especially among the young people of working
age. In recent years, many authors in scientific works have been highlighted
aspects of mutual development myofascial and autonomic dysfunction, which is
caused by neurophysiological preconditions and anatomical and topographical
relationships that need to be considered in the diagnostic and therapeutic
approaches. OBJECTIVE: To study the characteristics of the formation and flow of
autonomic dysfunction syndrome with paroxysmal and permanent types of flow in
patients with myofascial pain syndromes cervicobrachial localization. MATERIAL
AND METHODS: Using clinical neurological, vertebral neurological,
neuropsychological methods of studying the severity of pain (visual analogue
scale and Pain questionnaire of Mac Gill) examined 84 patients suffering from
autonomic dysfunction on the background of myofascial pain syndromes
cervicobrachial localization. To identify the features of vegetative regulation
of patients were divided into two groups: group 1 (51 people) - with a permanent
type of course; group 2 (33 patients) - a type of paroxysmal of course of
autonomic dysfunction. RESULTS: It was found more pronounced disturbances in
patients with paroxysmal type of course of autonomic dysfunction. The frequency
and severity of autonomic paroxysms associated with the severity of musculo-tonic
syndrome and location of active trigger points in the muscles of the neck and
shoulder girdle, due to anatomic and topographic features of these muscles,
namely the proximity of their location to the sympathetic formations neck. The
formation and development of emotional and affective disorders in both groups
played a significant role of pain and musculo-tonic syndrome. The syndrome of
autonomic dysfunction, in particular its paroxysmal type of flow, on the one hand
is a response to the development of myofascial pain syndromes cervicobrachial
localization, with another - a factor that facilitates the development of pain
and muscular-tonic syndromes, burdening the disease. CONCLUSION: In the diagnosis
and treatment of myofascial and autonomic dysfunction should take into account
comorbidity data of pathological conditions, which is important for developing
individual therapeutic regimens.
PMID- 28501831
TI - Resident attendance at weekly conferences after implementation of an optional
asynchronous learning curriculum.
PMID- 28501833
TI - [Psychometric and neurophysiological assessment of cognitive functions in
patients with epilepsy].
AB - BACKGROUND: The aim of the study was to assess cognitive functions in patients
with epilepsy using the neurophysiological method and psychological tests, and
analysis the relationship between clinical features of the disease and test
results. MATERIAL AND METHODS: The study included 31 patients with epilepsy aged
37.3+/-18.4 years. The control group consisted of 40 healthy volunteers aged
33.5+/-12.2 years. Cognitive functions were assessed using endogenous evoked
potential P300 and psychological tests - Mini-Mental State Examination (MMSE),
three subtests of Wechsler Adult Intelligence Scale-Revised (WAIS-R), Trail
Making Test (TMT), Benton Visual Retention Test (BVRT) and State-Trait Anxiety
Inventory (STAI). RESULTS: Epileptic patients achieved significantly lower scores
in all, except STAI-1, psychological tests in relation to the controls. A
correlation between age and TMT-A (p<0.050) and BVRT (p<0.050) was observed. The
disease duration affected results of MMSE (p<0.050), TMT-B (p<0.050) and BVRT
(p<0.050). Type of seizures was related to results of MMSE (p=0.005), type of
therapy - to results of STAI-1 (p=0.014) and TMT-B (p=0.008). The average latency
of P300 was significantly prolonged (p=0.00003) in epileptic patients (348+/
38ms) in relation to the controls (324+/-26ms). The relationship between P300 and
the duration of seizures (p=0.017) was observed. There was no correlation between
P300 and age, sex, frequency and type of seizures and therapy. A correlation
between P300 and TMT-B (p<0.050), BVRT-LPO(p<0.050) and STAI-1 (p<0.050) was
noticed. CONCLUSION: In epileptic patients cognitive impairment is often found.
It is advisable to perform regular neuropsychological testing; P300 can be used
only as a preliminary assessment.
PMID- 28501834
TI - [Etiology of bacterial infections and incidence of comorbidities in patients with
tuberculosis, treated in Mazovian Treatment Centre of Tuberculosis and Lung
Diseases during years 2012-2014].
AB - INTRODUCTION: Tuberculosis (TB) is an infectious disease caused by the
Mycobacterium tuberculosis. Infection occurs mostly via inhalation, while the
immune system is weakened. TB can take a pulmonary or extrapulmonary form.
Treatment involves an intensive, long-term antimycobacterial multidrug therapy.
TB cases are recorded on the worldwide scale. The morbidity in Poland varies
territorially. AIM: The analysis of bacterial infections and comorbidities cases
in the patients with TB, treated in Mazovian Treatment Centre of Tuberculosis and
Lung Diseases (MCLChPiG) during years 2012-2014. MATERIALS AND METHODS: The study
includes an analysis of 3093 cases of tuberculosis among MCLChPiG patients in
years 2012-2014, taking into account the age and gender of patients, forms of the
disease, bacterial superinfection in the course of TB (based on the results of
microbiological tests) and concomitant diseases. RESULTS: The study showed that
TB was more common in men (64.79%). Most cases have been diagnosed in the 50-65
year age group (31.65%). The most common form of TB among MCLChPiG patients was a
respiratory tract tuberculosis (96.61%), especially the pulmonary form (82.67%).
Concomitant diseases were diagnosed in 244 patients (7.89%), wherein tumors
(4.88%) were the most common ones. Bacterial superinfection in the course of TB
was observed in 149 patients (4.82%). The most frequently isolated bacteria were
H. influenzae (28.65%) and S. aureus (15.79%). CONCLUSIONS: Long-term
antimycobacterial treatment leads to the weakening of the patient's immune
system, which is a favorable condition for the development of bacterial
infections. Superinfection can be associated with concomitant disease, where
weakness of immunoresponsiveness increases the risk of developing TB. Bacteria
isolated from superinfections in the course of TB are mostly a typical pathogens
of the upper and lower respiratory tract.
PMID- 28501835
TI - [Possibility of using saliva as a diagnostic test material in cardiovascular
diseases].
AB - INTRODUCTION: Civilizational nature of the cardiovascular diseases, their
prevalence and social impact of complications resulting from late diagnosis force
to seek new faster and cheaper diagnostic methods. THE AIM: To present a
systematic review of the literature on studies of classical and new
cardiovascular diseases' risk markers in saliva. MATERIAL AND METHODS: Used
database Pubmed, Cochrane from 1980 to 2013 in search of clinical studies of
diagnostic tests for saliva in diseases of the cardiovascular system. RESULTS:
Saliva sampling for testing is done in a non-invasive and painless way, transport
and storage procedures are simpler and less expensive than blood. The diagnostic
tests necessary in the diagnosis and treatment of diseases of the cardiovascular
system can be performed in saliva. So far, the most promising diagnostic tests
are: hs CRP saliva, cortisol, CK-MB, troponin, myoglobin and other biomarkers of
inflammation. CONCLUSIONS: Biomarkers of the cardiovascular diseases may be
determined in saliva. The use of saliva in the diagnosis is possible and should
be applied both to screening assays, as well as in epidemiological and clinical
diagnostics.
PMID- 28501836
TI - [Bacopa Monnieri - activity and applications in medicine].
AB - Recently appeared medicinal preparations containing an extract of Bacopa
monnieri. B. monnieri has been used in the Ayurvedic system of medicine for
centuries, especially to enhance cognitive functions. Active compounds in this
plant include numerous saponins type dammarane, mainly bacoside A and B,
alkaloids and sterols. The pharmacological research of the extract of Bacopa
monnieri support traditional uses of this plant. The results of so far clinical
studies of the extract from B. monnieri, indicate to beneficial effect on memory,
learning and concentration in adults, children and to improve in anxiety and
depression after prolonged administration, although further clinical studies are
needed to confirm medical indications. It has been found to be well tolerated.
The present review summarizes current knowledge of mechanisms of actions also
presents of dietary supplements with B. monnieri.
PMID- 28501837
TI - [Hypochondria yesterday and today].
AB - The publication aims to discuss hypochondriacal disorders. This paper presents
the history of the concept of hypochondria from antiquity to modern times, also
includes brief information regarding etiopathogenesis, etiology, classification
and treatment of hypochondria with particular emphasis on psychotherapy. Our goal
was to make the subject hypochondriacal disorders, as a disease entity often
encountered in everyday medical practice.
PMID- 28501838
TI - [Pituitary disorders in elderly patients].
AB - The increase in life expectancy of about 30 years in the developed countries
represents one of the most important achievements of the last hundred years.
During aging, normal pituitary activity undergoes significant changes, reflecting
the complex relationship between aging and endocrine systems. These alterations
are postulated to be causally linked to human aging, possibly contributing to
changes in body composition, bone structure, physical performance, cardiovascular
system functions, and increased morbidity and mortality. Owing to age-dependent
physiological changes in pituitary function, as well as coexistent chronic
illness and polypharmacy, interpretation of pituitary function tests in older
adults is more difficult than in the younger. As symptoms of pituitary disorders
may overlap with what is considered to be ''normal aging,'' the presence of a
pituitary disorder in the elderly may often go undiagnosed. Unrecognized and
untreated pituitary disorders are associated with adverse outcomes that can be
ameliorated or prevented by adequate therapy. This paper summarizes the present
state of knowledge on the age-related changes in pituitary function, as well as
discusses the etiology, clinical manifestation, diagnosis, and management of
pituitary disorders in the elderly.
PMID- 28501839
TI - [Undernutrition in chronic respiratory diseases].
AB - Respiratory diseases such as asthma, COPD, lung cancer, infections, including
also tuberculosis constitute the most frequent diseases in the word.
Undernutrition frequently accompanies these diseases. Early diagnosis of
malnutrition and implementation of appropriate treatment is very important. A
nutritional interview and anthropometric examinations, such as body mass index,
fat free mass and fat mass are used to diagnose it. Nutritional therapy affects
the course and prognosis of these diseases. Diet should be individually adjusted
to the calculated caloric intake that increases during exacerbation of disease,
because of increased respiratory effort. Too large supply of energy can cause
increase metabolism, higher oxygen consumption and PaCO2 increase each dangerous
for patients with respiratory insufficiency. Main source of carbohydrates for
these patients should be products with low glycemic index and with high dietary
fiber contents. Large meals should be avoided since they cause rapid satiety,
abdominal discomfort and have negative impact on the work of the respiratory
muscles, especially of the diaphragm. Dietary supplements can be used in case of
ineffectiveness of diet or for the patients with severe undernutrition.
PMID- 28501840
TI - [The aging of the immune system].
AB - The age-related deterioration of health condition associated with progressive
impairment of innate and adaptive immunity was defined as the aging of the immune
system (also known as immunosenescence). Many changes occur within the immune
system with age, including in particular quantitative changes in populations and
subpopulations of cells resulting in dysfunction of the immune system. Elderly
patients often have chronic systemic low grade inflammation process which is an
effect of the inflammatory mediators secretion. Changes in the levels of
mediators have a negative impact on coexisting disease and body's ability to
fight infections. The purpose of the paper is to characterize the changes in
proportions and functions of immune cells during the aging.
PMID- 28501841
TI - [Nelson's Syndrome].
AB - Nelson's syndrome is a rare condition defined by enlargement of a pituitary
adenoma following bilateral adrenalectomy for treatment of Cushing disease.
Nelson's syndrome occurs at an incidence of 8-38% and is more frequent in younger
people. This syndrome is characterized by skin hyperpigmentation and very high
circulating levels of adrenocorticotrophic hormone. The pathophysiology of the
disease is still not fully understood, and it is unknown what factors drive
corticotroph cells in these patients. Presently, the syndrome is diagnosed at
earlier stages and therefore its clinical manifestation is less typical than in
the past. However, we can still find cases of full-blown Nelson's syndrome,
resulting from massive tumor growth and dramatically increased production of
adrenocorticotrophic hormone. Treatment of this syndrome largely consists of
surgery and/or radiotherapy because of the limited effectiveness of
pharmacotherapy. Although no guidelines have been published, it is reasonable to
perform pituitary imaging and to assess adrenocorticotrophic hormone in all
patients, particularly during the first years after bilateral adrenalectomy. The
purpose of this paper is to review the current views on the etiopathogenesis,
clinical presentation, diagnosis and treatment of Nelson's syndrome.
PMID- 28501842
TI - [Isolated vesical endometriosis - a case report].
AB - INTRODUCTION: Although endometriosis affects up to 15% of the female population
with childbearing potential, isolated endometriosis of the urinary tract is not a
frequent occurrence, as it involves only 1 to 2% of all endometriosis patients.
The chronic pelvic pain syndrome ultimately related to endometriosis is often
both a diagnostic and therapeutic challenge Materials and methods: This paper
presents the case of a female patient reporting with severe urinary symptoms.
Following cystoscopy and ultrasonography investigations, a suspected endometrioid
lesion of the urinary bladder has been evidenced. The patient-reported pain was
rated using a 10-point visual analogue scale (VAS). The patient has not received
pharmacotherapy. RESULTS: A partial laparoscopic full-thickness excision of the
urinary bladder wall with the evidenced lesion has been performed. The urinary
bladder wall has been sutured using two layers of sutures applied by laparoscopy.
Postoperative histopathology examination revealed a deep infiltrating
endometriosis lesion of the urinary bladder wall. Following surgery, the
patient's complaints have withdrawn completely, and no subsequent pharmacotherapy
was instated. DISCUSSION AND CONCLUSIONS: Isolated endometriosis of the urinary
tract, including the urinary bladder, is not a common pathology. Nevertheless, it
should always be taken into account in patients with dysuria or symptoms
suggestive of bladder malignancy. Total laparoscopic excision of the lesion
remains the treatment of choice, and in most cases provides patients with
complete withdrawal of symptoms, and only minimal incidence of recurrences, as
well as limited risk of early and delayed complications.
PMID- 28501843
TI - [Secondary osteoporosisn in boys with Alagille syndrome. Case report].
AB - Alagille syndrome is a multiorgan disorder, which especially manifests itself
with cholestasis, characteristic facial features, circulatory systems defects,
defects of the front segment of the eye, dysplastic changes in bones and kidneys
and impaired angiogenesis.The disease is caused by Jagged 1 gene mutation (JAG,
20p12 chromosome) which encodes ligand for Notch receptor. JAG/ Notch signaling
pathway plays important evolutionary role in cell differentiation in
organogenesis process . JAG1 expression in numerous tissues leads to multiorganic
manifestation. Jagged 1 expression is substantially important for skeleton growth
and bone cells activity. Its malfunction may lead to spine and long bones
abnormalities, neoplastic changes and osteoporosis. In this case report authors
present clinical (long bone fractures) and biochemical manifestations and
densitometric abnormalities ( decrease of bone mineral density) in 10 years old
boy with Alagille syndrome. Densitometry is suggested to be a good method in
early detection of mineralization disturbances in chronic cholestasis and
permanent monitoring of changes in bone structure is also very important.
PMID- 28501844
TI - [Diagnostics enigma: left ventricular noncompaction or systemic right ventricle?]
AB - A case of congenitally corrected transposition of great arteries, a rare
congenital heart defect diagnosed in an adult is presented and difficulties in
differential diagnosis of congenital heart defects in the adults are described.
The crucial point is proper interpretation of the echocardiography examination.
PMID- 28501845
TI - Medical terminology: Its size and typology.
AB - Medical terminology is one of the largest specialized terminologies and is
estimated to contain over 250,000 items. Classification of medical terminology
into six categories is proposed. The categories are as the following: (A) medical
terms that are a part of general basic lexicon of average native speaker (0.02
0.03 % of all terms), (B) specialized medical terms known by average physician
(about 45 % of all terms), (C) highly-specialized terms of subspecialties (about
15 % of all terms) (D) medical terms that primarily belong to other terminologies
(e.g. biological, chemical, physical, statistical) (about 20 % of all terms), (E)
medical slang (0.04-0.05 % of all terms), and (F) pharmaceutical terminology
(about 20 % of all terms).
PMID- 28501846
TI - [The 2nd conference 'Rare diseases not only in the curriculum', Szczecin -
Wroclaw, 26 and 30 May 2015].
AB - The 2nd conference 'Rare diseases not only in the curriculum', that took place on
26th May, 2015 in Pomeranian Medical University in Szczecin and 30 May in Wroclaw
Medical University. In accordance with the convention adopted at the first
conference in 2014 in Szczecin participants of the meeting realized the idea
expressed in the title of the conference by presenting issues of commonly known
rare diseases and those that are not discussed in the course of medical studies.
The active participants of the meeting were scientific workers medical schools in
Szczecin, Wroclaw and Bialystok, medical students and PhD students. The
significance of newborn screening in the early diagnosis of rare diseases in
children, possibilities of supporting children with genetically conditioned rare
diseases and their caregivers, application of guidelines of evidence-based
medicine in the process of diagnosing non-routine patients and methods of
physiotherapy of children with spinal muscular atrophy were discussed. Detailed
issues of diagnosing and treatment of many rare diseases were also presented,
among others Wilson disease, Alstrom syndrome, Cohen syndrome, Rubinstein-Taybi
syndrome, Cornelia de Lange syndrome, Poland syndrome, Netherton syndrome, inborn
aniridia and congenital arhinia - very rare defect requiring further scientific
studies.
PMID- 28501847
TI - [Activity Polish Physicians of Transcarpathian].
AB - The article presents the history of founding of the Organisation of Polish
Physicians of Transcarpathian and their participation in presentation of the
achievements of Polish Medical Sciences in Ukraine.
PMID- 28501848
TI - Mucinous adenocarcinoma and non-mucinous adenocarcinoma: differing
clinicopathological characteristics and computed tomography features in gastric
cancer.
AB - Mucinous gastric carcinoma (MGC) is a rare histological subtype of gastric
cancer. The clinicopathological characteristics and CT features of MGC remain
controversial. This study aimed to determine the clinicopathological
characteristics and CT features of MGC. We reviewed 62 patients with MGC and 104
patients with non-mucinous gastric carcinoma (NMGC), pathologically confirmed
between 2003 and 2015. There are significant differences in some
clinicopathological characteristics and CT features between MGC and NMGC. NMGC
occurs preferentially in males and more frequently in the lower third of the
stomach. Patients with MGC were characterized by larger tumor size, more advanced
tumor stages (II and III) and fewer lymphatic invasions. Layered enhancement
(83.3%) was the main pattern of MGC, while the most common pattern in NMGC was
homogeneous enhancement (52.6%), followed by heterogonous enhancement (34.6%).
The degree of enhancement of the inner layer in MGC was significantly higher than
in NMGC (DeltaCT of portal venous phase: 54.57 Hu vs. 47.19 Hu, P = 0.034), while
the middle or outer layer in MGC was significantly less enhanced (DeltaCT of
portal venous phase: 19.07 Hu vs. 33.09 Hu, P <0.001). Calcifications were more
common in MGC (P <0.001). ROC curves revealed that the most effective variables
in distinguishing MGC and NMGC were DeltaCT of the middle or outer layer in the
arterial phase (AUC=0.774) and portal venous phase (AUC=0.774), followed by the
attenuation value of the middle or outer layer in the unenhanced phase
(AUC=0.763). Calcifications had a high specificity (98.7%) in the diagnosis of
MGC. The accuracy (86.1%), sensitivity (83.3%) and specificity (87.2%) of layered
enhancement in diagnosing MGC were all high. Therefore, MGC was more likely to
have larger tumor size and more advanced tumor stage (II and III) than NMGC. The
thicker gastric wall, layered enhancement pattern and calcification were highly
suggestive CT features for differentiating MGC from NMGC.
PMID- 28501849
TI - miR-551b regulates epithelial-mesenchymal transition and metastasis of gastric
cancer by inhibiting ERBB4 expression.
AB - Epithelial-mesenchymal transition (EMT) is an important biological process that
is characteristic of malignant tumor cells with metastatic potential. We
investigated the role of miR-551b in EMT and metastasis in gastric cancer (GC).
We found that low miR-551b levels were associated with EMT, metastasis and a poor
prognosis in GC patients. Further, two GC cell lines, MNK45 and SGC7901,
exhibited lower miR-551b levels than the GES normal stomach cell line. Exposing
MNK45 and SGC7901 cells to TGF-beta1 resulted in cell morphology changes
characteristic of EMT, which was confirmed by Western blot analysis demonstrating
low E-Cadherin and high N-Cadherin and Vimentin levels. Treatment with miR-551b
mimics inhibited these EMT changes as well as Transwell migration and
invasiveness. We identified ERBB4 as a potential target of miR-551b based on
patient data from the TCGA. ERBB4 was upregulated in GC specimens, and its high
expression correlated with a poor prognosis of GC patients. Dual luciferase
assays revealed that miR-551b directly inhibited ERBB4 by binding to its 3'UTR.
Moreover, treatment with miR-551b mimics or the ERBB4 inhibitor AST-1306
inhibited EMT in the GC cell lines. Finally, nude mice xenografted with GC cancer
cell lines expressing miR-551b mimics exhibited smaller tumors and longer
survival than mice engrafted with control GC cancer cells. These data indicate
that miR-551b inhibits EMT and metastasis in GC by inhibiting ERBB4. miR-551b and
ERBB4 are thus potential therapeutic targets for the treatment of GC.
PMID- 28501852
TI - Clinically significant sub-clonality for common drivers can be detected in 26% of
KRAS/EGFR mutated lung adenocarcinomas.
AB - Genetic sub-clonality has been described in multiple malignancies, however the
presence of sub-clonality for major drivers in lung adenocarcinoma and its
clinical significance is a subject under debate. Using molecular and morphometric
approach, 347 lung adenocarcinoma samples were analyzed for KRAS and EGFR sub
clonality, which was further correlated with clinical and pathological
variables.KRAS and EGFR mutations were identified in 100 (29%) and 82 (23%)
cases, respectively. One hundred and forty four KRAS or EGFR positive cases were
also available for morphometric analysis, among which 37 (26%) were defined as
sub-clonal. The presence of sub-clonality was associated with shorter survival
time (p=0.02). Interestingly, cases with sub-clonality were also associated with
earlier disease stage (89% vs 66% stage I disease in sub-clonal vs clonal cases,
respectively, p=0.01) and less lymph node involvement (8% vs 25% in sub-clonal vs
clonal cases, respectively, p=0.02). Our findings demonstrate the presence of sub
clonality for mutations in common drivers in lung adenocarcinoma and link it both
to earlier disease stage and to poor survival. These findings are in line with
the different evolutionary models that can present with genetic sub-clonality.
PMID- 28501851
TI - Implementing liquid biopsies into clinical decision making for cancer
immunotherapy.
AB - During the last decade, novel immunotherapeutic strategies, in particular
antibodies directed against immune checkpoint inhibitors, have revolutionized the
treatment of different malignancies leading to an improved survival of patients.
Identification of immune-related biomarkers for diagnosis, prognosis, monitoring
of immune responses and selection of patients for specific cancer immunotherapies
is urgently required and therefore areas of intensive research. Easily accessible
samples in particular liquid biopsies (body fluids), such as blood, saliva or
urine, are preferred for serial tumor biopsies.Although monitoring of immune and
tumor responses prior, during and post immunotherapy has led to significant
advances of patients' outcome, valid and stable prognostic biomarkers are still
missing. This might be due to the limited capacity of the technologies employed,
reproducibility of results as well as assay stability and validation of results.
Therefore solid approaches to assess immune regulation and modulation as well as
to follow up the nature of the tumor in liquid biopsies are urgently required to
discover valuable and relevant biomarkers including sample preparation, timing of
the collection and the type of liquid samples. This article summarizes our
knowledge of the well-known liquid material in a new context as liquid biopsy and
focuses on collection and assay requirements for the analysis and the technical
developments that allow the implementation of different high-throughput assays to
detect alterations at the genetic and immunologic level, which could be used for
monitoring treatment efficiency, acquired therapy resistance mechanisms and the
prognostic value of the liquid biopsies.
PMID- 28501854
TI - Dual-negative expression of Nrf2 and NQO1 predicts superior outcomes in patients
with non-small cell lung cancer.
AB - Functional studies in non-small cell lung cancer (NSCLC) patients revealed that
hyperactivation of the NF-E2-related factor 2 (Nrf2) pathway facilitates tumor
growth. We examined the usefulness of Nrf2 and NQO1 as indicators of prognosis in
NSCLC. Tumor and adjacent non-tumor tissue samples were collected from 215 NSCLC
patients who had tumor resections between 2006 and 2011. Immunohistochemistry was
performed to detect Nrf2 or NQO1 expression. The correlation between Nrf2 or NQO1
expression and survival outcomes was evaluated using the Kaplan-Meier method and
Cox proportional hazards regression model. Levels of Nrf2 and NQO1 were elevated
in tumor tissues. In particular, Nrf2 was elevated in nearly all tumor cells.
NQO1 expression positively correlated with Nrf2 expression (P = 0.039). Nrf2
expression positively correlated with lymph node metastasis (P = 0.001) and
negatively correlated with tumor differentiation (P = 0.032). As compared with
either Nrf2 or NQO1 alone, dual-negative expression of Nrf2 and NQO1 was more
predictive of superior overall survival (P = 0.020) and disease free survival (P
= 0.037). Subgroup analyses showed that females, nonsmokers, and patients with
advanced-stage NSCLC were suitable populations in which to evaluate prognosis
based on Nrf2 and NQO1 co-expression. These results indicate that dual-negative
expression of Nrf2 and NQO1 is predictive of a better prognosis in NSCLC
patients.
PMID- 28501855
TI - Extracellular pH is a biomarker enabling detection of breast cancer and liver
cancer using CEST MRI.
AB - Extracellular pH (pHe) decrease is associated with tumor growth, invasion,
metastasis, and chemoresistance, which can be detected by chemical exchange
saturation transfer (CEST) magnetic resonance imaging (MRI). Here, we
demonstrated that ioversol CEST MRI can be exploited to achieve pHe mapping of
the liver cancer microenvironment. In in vitro studies, we firstly explored
whether ioversol signal is pH-dependent, and calculated the function equation
between the CEST effects of ioversol and pH values, in the range of 6.0 to 7.8,
by a ratiometric method. Then we verified the feasibility of this technique and
the equation in vivo by applying pHe imaging in an MMTV-Erbb2 transgenic mouse
breast cancer model, which is often used in CEST pHe studies. Furthermore, in
vivo ioversol CEST MRI, we were able to map relative pHe and differentiate
between tumor and normal tissue in a McA-RH7777 rat hepatoma model. This suggests
pHe may be a useful biomarker for human liver cancer.
PMID- 28501856
TI - Prognostic significance of subclassification of stage IIB lung cancer: a
retrospective study of 226 patients.
AB - We investigated the prognostic significance of subclassification of stage IIB
lung cancer according to the eighth tumor-node-metastasis (TNM) classification.
To this purpose, the prognostic outcomes of 226 stage IIB lung cancer patients
who underwent surgery without adjuvant therapies between 2001 and 2010 were
evaluated retrospectively based on the eighth TNM classification. Of the 226
patients, 23, 30, 118 and 55 had pT1b, pT1c, pT2a, and pT2b stage cancers,
respectively. Their 5-year survival rates were 67%, 33%, 21%, and 27%,
respectively. There was no significant difference in the 5-year survival between
T1b and T1c, between T1c and T2a, and between T2a and T2b (p = 0.128, 0.105, and
0.403, respectively). There were significant differences in the 5-year survival
between T1b and T2a, between T1b and T2b, and between T1c and T2b (p = 0.005,
0.002, and 0.042, respectively). The 5-year survival of patients with pleural
invasion and vessel invasion was significantly worse than that of their
counterparts (p = 0.009 and <0.001, respectively). Subclassification of stage IIB
lung cancer is of prominent prognostic significance. It is recommended that the
current stage be subclassified, in order to more accurately predict the prognosis
of patients.
PMID- 28501858
TI - The Interdisciplinary Chronic Kidney Disease Clinic: End of the Beginning, Not
Beginning of the End.
PMID- 28501859
TI - Molecular Insights into Covalently Stained Carious Dentine Using Solid-State NMR
and ToF-SIMS.
AB - Dyes currently used to stain carious dentine have a limited capacity to
discriminate normal dentine from carious dentine, which may result in
overexcavation. Consequently, finding a selective dye is still a challenge.
However, there is evidence that hydrazine-based dyes, via covalent bonds to
functional groups, bind specifically to carious dentine. The aim of this study
was to investigate the possible formation of covalent bonds between carious
dentine and 15N2-hydrazine and the hydrazine-based dye, 15N2-labelled Lucifer
Yellow, respectively. Powdered dentine from extracted carious and normal teeth
was exposed to the dyes, and the staining reactions were analysed using time-of
flight secondary ion mass spectrometry (ToF-SIMS), solid-state 13C-labelled
nuclear magnetic resonance (NMR) and 15N-NMR spectroscopy. The results showed
that 15N2-hydrazine and 15N2-labelled Lucifer Yellow both bind to carious dentine
but not to normal dentine. It can thus be concluded that hydrazine-based dyes can
be used to stain carious dentine and leave normal dentine unstained.
PMID- 28501857
TI - Combined treatment with artesunate and bromocriptine has synergistic anticancer
effects in pituitary adenoma cell lines.
AB - Prolactinomas are the most prevalent functional pituitary adenomas. The preferred
treatments for prolactinomas are dopamine agonists (DAs) such as bromocriptine
(BRC), but DAs still have the challenges of tumor recurrence and drug resistance.
This study demonstrates that the synergy of function and mechanism between
artesunate (ART) and BRC inhibits prolactinoma cell growth in vitro. We found
that low-dose ART combined with BRC synergistically inhibited the growth of GH3
and MMQ cell lines, caused cell death, attenuated cell migration and invasion,
and suppressed the expression of extracellular prolactin. The induction of
apoptosis after co-treatment was confirmed by immunofluorescent staining,
assessment of caspase-3 protein expression, and flow cytometry. Expression of miR
200c, a carcinogenic factor in pituitary adenoma, was reduced following co
treatment with ART and BRC. This was accompanied by increased expression of the
antitumor factor Pten. Transfection experiments with miR-200c analogs and
inhibitors confirmed that miR-200c expression was inversely associated with Pten
expression. We suggest that ART and BRC used in combination exert synergistic
apoptotic and antitumor effects by suppressing miR-200c and stimulating Pten
expression.
PMID- 28501860
TI - Single-Center Experience with Intimal Sarcoma, an Ultra-Orphan, Commonly Fatal
Mesenchymal Malignancy.
AB - BACKGROUND: Intimal sarcoma is a rare malignancy that, clinically and
radiographically, often mimics pulmonary embolism. The intravascular tumor tends
to disseminate rapidly and metastases can be present at first diagnosis. METHODS:
We reviewed all cases of intimal sarcoma that were diagnosed, treated and
followed at the University Hospitals Leuven between April 2006 and April 2016.
RESULTS: We identified 13 patients with a median age of 51 years. In 6 patients
initial findings were suggestive of thromboembolic disease. Platelet-derived
growth factor receptor alpha (PDGFRA) amplification was the most prevalent
molecular finding, present in 11 patients. The MDM2 gene was amplified in 9
cases, and the EGFR gene in 3 patients. The median overall survival was 13
months. 11 patients underwent surgery. In 5 cases with inoperable and/or
metastatic disease chemotherapy was given. Treatment with imatinib was initiated
in 4 patients. CONCLUSIONS: Intimal sarcoma is an extremely rare and aggressive
malignancy that has a very poor prognosis. Mimicking thromboembolic disease,
diagnosis and treatment can be delayed. Surgery is the mainstay of treatment but
is seldom curative. The disease is highly resistant to cytotoxic and targeted
treatment. Given the fact that intimal sarcoma commonly expresses more than 1
molecular target, combination therapy might be an option, although toxicity may
be a limitation.
PMID- 28501861
TI - Pre-End-Stage Renal Disease Care and Early Survival among Incident Dialysis
Patients in the US Military Health System.
AB - BACKGROUND: Previous reports showed an increased early mortality after chronic
dialysis initiation among the end-stage renal disease (ESRD) population. We
hypothesized that ESRD patients in the Military Health System (MHS) would have
greater access to pre-ESRD care and hence better survival rates during this early
high-risk period. METHODS: In this retrospective cohort study, using the US Renal
Data System database, we identified 1,256,640 patients initiated on chronic
dialysis from January 2, 2004 through December 31, 2014, from which a bootstrap
sample of 3,984 non-MHS incident dialysis patients were compared with 996 MHS
patients. We assessed care by a nephrologist and dietitian, erythropoietin
administration, and vascular access use at dialysis initiation as well as all
cause mortality as outcome variables. RESULTS: MHS patients were significantly
more likely to have had pre-ESRD nephrology care (adjusted OR [aOR] 2.9; 95% CI
2.3-3.7) and arteriovenous fistula used at dialysis initiation (aOR 2.2; 95% CI
1.7-2.7). Crude mortality rates peaked between the 4th and the 8th week for both
cohorts but were reduced among MHS patients. The baseline adjusted Cox model
showed significantly lower death rates among MHS vs. non-MHS patients at 6, 9,
and 12 months. This survival advantage among MHS patients was attenuated after
further adjustment for pre-ESRD nephrology care and dialysis vascular access.
CONCLUSIONS: MHS patients had improved survival within the first 12 months
compared to the general ESRD population, which may be explained in part by
differences in pre-ESRD nephrology care and vascular access types.
PMID- 28501862
TI - Chromosome Painting in Trogon s. surrucura (Aves, Trogoniformes) Reveals a
Karyotype Derived by Chromosomal Fissions, Fusions, and Inversions.
AB - Trogons are forest birds with a wide distribution, being found in Africa, Asia,
and America, and are included in the order Trogoniformes, family Trogonidae.
Phylogenetic studies using molecular data have not been able to determine the
phylogenetic relationship among the different genera of trogons. So far, no
cytogenetic data for these birds exist. Hence, the aim of this study was to
characterize the karyotype of Trogon surrucura surrucura by means of classical
and molecular cytogenetics. We found a diploid chromosome number of 2n = 82,
similar to most birds, with several derived features compared to chicken and the
putative ancestral avian karyotype. T. s. surrucura showed 3 pairs of
microchromosomes bearing 18S rDNA clusters. The Z and W sex chromosomes were of
similar size but could readily be identified by morphological differences. Using
chromosome painting with whole chromosome probes from Gallus gallus and
Leucopternis albicollis, we found that the chromosomes homologous to chicken
chromosomes 2 and 5 correspond to 2 different pairs in T. s. surrucura and L.
albicollis, due to the occurrence of centric fissions. Paracentric inversions
were detected in the segment homologous to chicken chromosome 1q, and we
confirmed the recurrence of breakpoints when our results were compared to other
species of birds already analyzed by FISH or by in silico genome assembly.
PMID- 28501863
TI - Psychometric Properties of the Revised Illness Perception Questionnaire for Oral
Health.
AB - AIMS: The aim of this study was to test the hypothesis that, for patients with
dental caries, the Spanish version of the Revised Illness Perception
Questionnaire for Oral Health (IPQ-R-OH) has 7 dimensions, including personal and
treatment control, timeline-acute/chronic and timeline-cyclical, illness
coherence, consequences, and emotional representations. METHODS: A Spanish
adaptation of the IPQ-R, with a self-reported 38-item scale, was developed.
Exploratory and confirmatory factor analyses were conducted using data from 520
patients with dental caries attending the Dental Clinic at Universidad
Cooperativa de Colombia, Pasto, Colombia. RESULTS: Exploratory factor analysis
revealed 7 dimensions with 36 items (2 items were removed because of poor factor
loadings or discriminant ability). The internal consistency coefficients of each
factor ranged from 0.72 to 0.91, and all item loadings were >0.52. Confirmatory
factor analysis indicated that a 7-factor model with 36 items had superior fit
compared to the 38-item original model: chi2 = 1,784.291 (df = 573, p < 0.001);
nonnormal fit index = 0.941; comparative fit index = 0.946; root mean square
error of approximation = 0.062 (90% CI = 0.057-0.066); standardized root mean
square residual = 0.072; and Akaike information criterion = 638.291. Control
(integrated by items from personal control, treatment control, and timeline-acute
factors) and hopelessness (PC15 and PC17) were the 2 reconfigured factors that
were identified. CONCLUSIONS: These findings suggest that the modified 36-item
model has satisfactory reliability and construct factorial validity; therefore,
it could be a valuable instrument in the screening of illness perceptions in oral
health.
PMID- 28501864
TI - First-Line Support by Intra-Aortic Balloon Pump in Non-Ischaemic Cardiogenic
Shock in the Era of Modern Ventricular Assist Devices.
AB - OBJECTIVES: Little is known about circulatory support in cardiogenic shock (CS)
from other causes than the acute coronary syndrome or after cardiotomy. We
evaluated the effects of first-line intra-aortic balloon pump (IABP) support in
this subpopulation of CS patients. METHODS: A retrospective study was performed
in 27 patients with CS from end-stage cardiomyopathy supported firstly by IABP in
the years 2011-2016. RESULTS: At 24 h, lactate decreased from 3.2 (2.1-6.8) to
1.8 (1.2-2.2) mmol/L (p < 0.001). Eighteen patients (67%) defined as IABP
responders were successfully bridged to either recovery (n = 7), left ventricular
assist device (n = 5), or heart transplantation (n = 6). IABP failed in 9
patients (non-responders, 33%) who either died (n = 7) or needed support by
extracorporeal membrane oxygenation (n = 2). At 24 h of IABP support, urinary
output was higher (2,660 [1,835-4,440] vs. 1,200 [649-2,385] mL; p = 0.02) and
fluid balance more negative (-1,564 [-2,673 to -1,086] vs. -500 [-930 to +240]
mL; p < 0.001) in responders than non-responders. Overall survival at 1 year was
63%. CONCLUSION: In most patients, first-line support by IABP in end-stage
cardiomyopathy is associated with improvement in organ perfusion and clinical
stabilisation for at least 24 h allowing time for decision making on next
therapies.
PMID- 28501866
TI - Clinical Factors Associated with Readmission among Patients with Lower Limb
Cellulitis.
AB - BACKGROUND: There is substantial allocation of resources directed towards
evaluation and management of lower limb cellulitis (LLC) in the acute care
setting. Readmission for LLC is poorly understood, and there is little evidence
with which to identify patients at risk for readmission. OBJECTIVE: To describe
demographics, comorbidities, admission vital signs, and laboratory markers of
infection among patients with LLC who are readmitted, and to investigate which
among these factors is associated with readmission. METHODS: A cross-sectional
retrospective cohort study was performed at tertiary and community hospitals
within a regional health care system in order to summarize readmission
characteristics. Univariate and multivariate models were created to estimate the
likelihood of independent variables being associated with LLC readmission.
RESULTS: The readmission rate was 11.2% with a median age of 68.6 years for the
cohort. Increased age and subsidized insurance were associated with more frequent
admissions. For every 10-year age increase, cellulitis subjects had a 14%
increase in readmission odds (OR 1.14, CI 1.07-1.20). Patients with subsidized
insurance had an almost twofold increased risk (OR 1.88, CI 1.42-2.50). Smoking,
obesity, hypertension, diabetes mellitus, renal insufficiency, tachycardia,
hypotension, leukocytosis, and neutrophilia were not more frequent in readmitted
patients. CONCLUSIONS: Older age and subsidized insurance were associated with
readmission whereas severity indicators for infection including abnormal vital
signs and laboratory markers were not significantly associated. Factors other
than severity of infection, such as socioeconomic factors, may influence clinical
decisions related to readmission for LLC.
PMID- 28501867
TI - Could End-Tidal CO2 Predict Percutaneous Mitral Valve Repair?
PMID- 28501865
TI - Fresh and Frozen-Thawed Embryo Transfer Compared to Natural Conception:
Differences in Perinatal Outcome.
AB - BACKGROUND/AIM: To compare the pregnancy outcome of singletons conceived after
transfer of cryopreserved and thawed embryos (frozen embryo transfer [FET]) to
singletons conceived after fresh embryo transfer (fresh ET) and natural conceived
singletons. METHODS: Using a retrospective data analysis on a study population
consisting of 1,261 singletons born after FET and 2,519 singletons born after
fresh ET between 2006 and 2015. The control group consisted of singletons born
after natural conception. Main outcome measures consisted of birth weight (in
grams), gestational age, preterm birth (<37 weeks of gestation), being large for
gestational age (LGA, above 90th weight percentile adjusted for gestational age)
and Apgar scores. RESULTS: Babies born after FET had an increased risk of high
birth weight (adjusted OR [AOR]) 2.92; 1.503-3.482) and being LGA (AOR fresh ET
vs. FET 1.47; 1.210-1.787) compared to singletons born after fresh ET, as well as
higher birth weights compared to natural conceived children. CONCLUSIONS:
Singletons born after FET have a higher risk of high birth weight and being LGA
compared to singletons after fresh ET and compared to natural conceived
singletons. We assume that the freezing process might be the underlying cause.
PMID- 28501868
TI - Factors Associated with Potassium-Competitive Acid Blocker Non-Response in
Patients with Proton Pump Inhibitor-Refractory Gastroesophageal Reflux Disease.
AB - BACKGROUND/AIMS: Approximately 20-40% of patients with gastroesophageal reflux
disease (GERD) are refractory to proton pump inhibitor (PPI) treatment. The acid
inhibitory effect of vonoprazan, a novel potassium-competitive acid blocker (P
CAB), is significantly greater when compared to the effect of PPIs. We
investigated the efficacy of vonoprazan treatment for PPI-refractory GERD and
factors associated with P-CAB non-response. METHODS: We enrolled 277 GERD
patients receiving continuous PPI therapy. Subjects completed a self-report
questionnaire including the frequency scale for the symptoms of GERD (FSSG).
Patients with PPI-refractory GERD received 20 mg of vonoprazan once daily for 8
weeks. After that, subjects completed the same questionnaire, and the results
were used to identify P-CAB responders and non-responders. RESULTS: Twenty-eight
patients were identified as P-CAB responders and 26 were non-responders.
Vonoprazan treatment significantly decreased scores of FSSG, nighttime symptom,
and Athens Insomnia Scale. Multivariate analysis demonstrated co-existing
functional dyspepsia (FD; OR 4.94) and the presence of sleep disturbances (OR
4.34) was associated with P-CAB non-response, whereas alcohol consumption was
inversely associated. CONCLUSIONS: Vonoprazan treatment might be appropriate as a
promising new strategy for PPI-refractory GERD. Co-existing FD, sleep
disturbances, and alcohol abstinence were significantly associated with P-CAB non
response. Other therapeutic options should be considered in patients with these
factors.
PMID- 28501869
TI - Intramuscular versus Vaginal Progesterone Administration in Medicated Frozen
Embryo Transfer Cycles: A Randomized Clinical Trial Assessing Sub-Endometrial
Contractions.
AB - OBJECTIVE: The study aimed to assess whether sub-endometrial contractility is
reduced by the use of intramuscular (IM) progesterone. DESIGN: This is a
randomized clinical trial. Patients assigned to a medicated day 5 frozen embryo
transfer (FET) were randomly allocated to "vaginal progesterone" or "IM
progesterone": patients randomized to the vaginal arm were treated with 200 mg
micronized progesterone 3 times daily while patients randomized into the IM
progesterone arm were treated with a single daily injection of 50 mg progesterone
in oil. The main outcome measure was the number of sub-endometrial contractions
(waves) per minute 1 day before a blastocyst embryo transfer. RESULTS: Thirty
four patients were enrolled. The progesterone serum concentration was
significantly higher in patients using the IM progesterone (85.2 +/- 50.1 vs.
30.3 +/- 11.2 nmol/L, respectively) but this did not translate into a lower sub
endometrial contractility (2.4 +/- 4.8 vs. 1.4 +/- 1.1 contraction/min,
respectively). Clinical pregnancy rates were comparable between groups. The
number of sub-endometrial waves was significantly lower among pregnant patients
(p = 0.02). CONCLUSIONS: The use of IM progesterone in medicated FET cycles does
not reduce the sub-endometrial activity compared to vaginal progesterone
administration. Our data support a poor clinical pregnancy outcome with high wave
activity, regardless of the progesterone mode.
PMID- 28501870
TI - Long Non-Coding RNA XLOC_008466 Functions as an Oncogene in Human Non-Small Cell
Lung Cancer by Targeting miR-874.
AB - BACKGROUND: The therapy and prognosis of lung cancer are difficult because of
multiple genetic and epigenetic alterations. Long non-coding RNAs (lncRNAs) have
been verified as new mediators of cancer development and progression by virtue of
their various functions. Here, we focused on the lncRNA XLOC_008466 based on
previous microarray data. However, whether aberrant expression of XLOC_008466 in
human non-small cell lung cancer (NSCLC) is correlated with malignancy,
metastasis or prognosis has not been elucidated. METHODS: We performed real-time
PCR, CCK-8, flow cytometry, trans-well, western blotting, luciferase reporter
assays, RNA immunoprecipitation (RIP) assay and surface plasmon resonance (SPR)
assay to detect the function of XLOC_008466 in NSCLC. RESULTS: Up-regulation of
XLOC_008466 in NSCLC patients was related to lymph node metastasis and the TNM
stage. In vitro, down-regulation of XLOC_008466 inhibited cell proliferation and
invasion of A549 and H460 cells in vitro, but promoted cell apoptosis.
Experiments on mechanisms revealed that XLOC_008466 functioned as a ceRNA,
directly binding to miR-874, and could affect cell proliferation, apoptosis and
invasion through regulation of miR-874 expression as well as by increasing matrix
metalloproteinase 2 (MMP2) and X-linked inhibitor of apoptosis (XIAP) expression.
CONCLUSIONS: XLOC_008466 functions as an oncogene in NSCLC by regulating the miR
874-MMP2/XIAP axis, which indicates that XLOC_008466 may be a useful marker and
potential therapeutic target in NSCLC.
PMID- 28501871
TI - Percutaneous Closure in Conal Septal Ventricular Septal Defects: Fact or Fiction?
PMID- 28501872
TI - A Mechanism Study Underlying the Protective Effects of Cyclosporine-A on Lung
Ischemia-Reperfusion Injury.
AB - AIM: This study is aimed at validating the hypothesis that administration of
cyclosporine-A (CsA) would be protective in lung ischemia-reperfusion (I/R)
injury and in exploring the underlying mechanism. METHODS: Rabbits were divided
into 4 groups: the control, sham operation, I/R, and I/R with CsA treatment. Flow
cytometry was used to measure the mitochondrial membrane potential. Laser
scanning confocal microscope was used to analyze mitochondrion permeability
transition pore (MPTP). The apoptotic cell was detected by the TUNEL staining.
Western blot was performed to analyze the protein expression levels. RESULTS: CsA
not only attenuated the histopathologic alterations in lung and mitochondria
after I/R injury, but also attenuated I/R injury through increasing MPP and
inhibiting MPTP opening. Besides, CsA attenuated I/R injury through suppressing
the release of cytochrome-c (CytC), inhibiting cell apoptosis and decreasing the
expression levels of cyclophilin-D (Cyp-D), adenine nucleotide translocase 1
(ANT1) and voltage-dependent anion channel 1 (VDAC1). Finally, we found that Cyp
D knockdown inhibits I/R injury-induced MPTP opening and cell apoptosis.
CONCLUSION: Our study found that the protective role of CsA on lung I/R injury
depends on the inhibition of MPTP and CytC release, suppression of the activation
of mitochondrial apoptosis pathway and the expressions of apoptotic-related
proteins, as well as the decreased expression levels of ANT1 and VDAC1.
PMID- 28501873
TI - Comparisons of Risk Factors for Intracerebral Hemorrhage versus Ischemic Stroke
in Chinese Patients.
AB - BACKGROUND: Chinese populations have a higher stroke incidence, a higher
proportion of intracerebral hemorrhage (ICH), and a lower proportion of ischemic
stroke (IS) as compared with white populations. The reasons are not fully
understood. METHODS: To evaluate the differences of major risk factors between
ICH and IS in Chinese stroke patients, we analysed acute ICH and IS patients
consecutively recruited in National Taiwan University Hospital Stroke Registry
from 2006 to 2011. We used multiple logistic regression models to examine the
associations of risk factors with ICH vs. IS. Also, we conducted subgroup
analyses when a strongly significant interaction was detected. RESULTS: We
included a total of 1,373 ICH and 4,953 IS patients. ICH patients were younger
than IS patients (mean age 61 vs. 68 years, p < 0.001), but there was no
significant difference in gender (males 62 vs. 59%, p = 0.064). A logistic
regression model adjusted for age, gender, and other major risk factors showed
that both hypertension (OR 2.23, 95% CI 1.74-2.87) and alcohol intake (OR 1.44,
95% CI 1.16-1.77) had significantly stronger associations with ICH than IS,
whereas diabetes, atrial fibrillation, ischemic heart disease, hyperlipidemia,
smoking, and transient ischemic attack were less associated with ICH than IS. In
subgroup analyses, the association of hypertension with ICH vs. IS was more
marked in younger patients. CONCLUSION: Hypertension and alcohol intake are more
strongly associated with ICH than IS in Chinese stroke patients, especially in
younger patients.
PMID- 28501874
TI - Screening Tool for Early Postnatal Prediction of Retinopathy of Prematurity in
Preterm Newborns (STEP-ROP).
AB - BACKGROUND: Retinopathy of prematurity (ROP) is a disorder of the preterm newborn
characterized by neurovascular disruption in the immature retina that may cause
visual impairment and blindness. OBJECTIVE: To develop a clinical screening tool
for early postnatal prediction of ROP in preterm newborns based on risk
information available within the first 48 h of postnatal life. METHODS: Using
data submitted to the Vermont Oxford Network (VON) between 1995 and 2015, we
created logistic regression models based on infants born <28 completed weeks
gestational age. We developed a model with 60% of the data and identified birth
weight, gestational age, respiratory distress syndrome, non-Hispanic ethnicity,
and multiple gestation as predictors of ROP. We tested the model in the remaining
40%, performed tenfold cross-validation, and tested the score in ELGAN study
data. RESULTS: Of the 1,052 newborns in the VON database, 627 recorded an ROP
status. Forty percent had no ROP, 40% had mild ROP (stages 1 and 2), and 20% had
severe ROP (stages 3-5). We created a weighted score to predict any ROP based on
the multivariable regression model. A cutoff score of 5 had the best sensitivity
(95%, 95% CI 93-97), while maintaining a strong positive predictive value (63%,
95% CI 57-68). When applied to the ELGAN data, sensitivity was lower (72%, 95% CI
69-75), but PPV was higher (80%, 95% CI 77-83). CONCLUSIONS: STEP-ROP is a
promising screening tool. It is easy to calculate, does not rely on extensive
postnatal data collection, and can be calculated early after birth. Early ROP
screening may help physicians limit patient exposure to additional risk factors,
and may be useful for risk stratification in clinical trials aimed at reducing
ROP.
PMID- 28501875
TI - Five-Year Neuropsychological Outcome after Stereotactic Radiofrequency
Amygdalohippocampectomy for Mesial Temporal Lobe Epilepsy: Longitudinal Study.
AB - PURPOSE: To assess the neuropsychological performance recoded over a period of 5
years after stereotactic radiofrequency amygdalohippocampectomy (SAHE) in the
treatment of mesial temporal lobe epilepsy. MATERIAL AND METHODS: Thirty patients
(mean age 38 years, 14 females/16 males) were included in this study. Twenty-one
patients were treated on the left side, 9 on the right. Patients underwent
neuropsychological evaluation by the Wechsler Adult Intelligence Scale-Revised
and the Wechsler Memory Scale-Revised preoperatively and 5 years after SAHE.
RESULTS: Twenty-three (77%) patients were classified as Engel class I. At the
group level, we found significant increases in all intelligence domains (Global,
Visual, and Performance) by 19.1 (7.4), 15.8 (6.1), and 19.1 (7.9) points,
respectively. Significant improvements were also detected in all memory measures
(Global, Verbal, Visual, Attention/Concentration, Delayed Recall) by 19.4 (14.2),
16.9 (13.3), 19.0 (14.7), 15.3 (15.0), and 24.6 (13.4), respectively. Patients
with left-sided surgery improved significantly more in Attention/Concentration.
Otherwise, there were no statistically significant differences in memory function
improvements between subgroups according to the operated side. CONCLUSION: After
SAHE, we found favorable long-term neuropsychological outcomes. These results
could be caused by incomplete destruction of target structures and minimization
of collateral damage that possibly enables adaptive postoperative neuronal
reorganization.
PMID- 28501876
TI - Stereotactic Radiosurgery as Initial Surgical Management for Elderly Patients
with Trigeminal Neuralgia.
AB - BACKGROUND: Management of older patients with medically refractory trigeminal
neuralgia (TN) is yet a matter of debate. OBJECTIVE: We sought to determine the
benefit of stereotactic radiosurgery (SRS) as the sole surgical management in
older patients (>=70 years). METHODS: One hundred and twenty-seven patients (>=70
years) with typical TN underwent SRS as initial surgical management. The median
maximum dose for the first procedure was 80 Gy. Repeat SRS was performed in 46
patients who developed recurrent pain. RESULTS: After the first SRS, the initial
pain control was achieved in 91% of patients. Complete pain relief (Barrow
Neurological Institute [BNI] score I) developed in 75 patients (59%) and was
maintained in 59, 39, and 22% of patients at 1, 3, and 5 years. Following repeat
SRS, the rate of complete pain relief was 79, 55, and 41% at 1, 3, and 5 years.
The chance of BNI I preservation was greater after repeat SRS compared to initial
SRS (hazards ratio: 2.02, p < 0.0001). The incidence of trigeminal sensory loss
was 17% after initial SRS but increased to 39% after repeat SRS. CONCLUSIONS: SRS
alone was used effectively in older TN patients to achieve pain control.
Recurrent pain responded to retreatment but was associated with an increased risk
of sensory dysfunction.
PMID- 28501877
TI - Association Between Sex and Speech Auditory Brainstem Responses in Adults, and
Relationship to Sex Hormone Levels.
AB - BACKGROUND The aim of this study was to investigate the association between sex
and speech-ABR in adults, and its relationship to sex hormone levels. MATERIAL
AND METHODS Speech-ABR were elicited with the consonant-vowel syllable (/da/) in
a total of 35 adults. Reproductive hormone levels were also measured. RESULTS The
transient response of the speech-ABR (waves V, A, and O) in females show a
shorter latency (waves V, A and O) and a larger amplitude (waves V and A) than in
males (P<0.05), except for the amplitude of peak O (P>0.05). The sustained
response of females exhibited a larger amplitude (wave F, P<0.05) and a shorter
latency (wave D, E, and F, P<0.05) than in males, except for the amplitude of
peak D and E (P>0.05). The latencies of speech-ABR were positively correlated
with testosterone level (P<0.05), and were negatively correlated with estradiol
(E2) levels (P<0.05), except for wave E (P>0.05). The E2 showed a positive
correlation with the absolute value of amplitude of the speech-ABR (P < 0.05). On
the contrary, total testosterone showed a negative correlation with the absolute
value of amplitude the speech-ABR (P<0.05), except for wave D and wave O
(P>0.05). CONCLUSIONS Sex differences in speech-ABR are significant in adults.
The latencies and amplitude of the speech-ABR waves were correlated with the E2
concentration and testosterone level. The sex hormones likely affect speech
encoding in the brainstem.
PMID- 28501878
TI - [Oral manifestations of ulcerative colitis].
AB - Ulcerative colitis is an inflammatory bowel disease occurring relatively
frequently in industrialised regions of the world. Pyostomatitis vegetans is the
most characteristic pathognomonic oral manifestation but other oral abnormalities
like aphthous lesions, caries and periodontitis are more prevalent in patients
with ulcerative colitis. Oral care providers must be aware of these problems if
they are to provide adequate oral care.
PMID- 28501879
TI - [Implant-supported 3D-printed bridge in the edentulous maxilla].
AB - A healthy 72-year-old man presented with retention problems concerning the
dentures in his maxilla. On account of extreme resorption, placement of implants
without prior bone augmentation was not an option. The proposal was to use
autologous bone harvested from the iliac crest. After a healing period of 4
months, a cone beam computed tomography scan was made, following which the
virtual implant planning of 6 implants was carried out. With the help of a
template supported by osteosynthesis screws, which had already been inserted
during the augmentation procedure, the plan was applied to the patient. The
precision of the fit between the planning and the actual placement of the
implants has become so high that it was decided to place a 3D-printed dental
bridge immediately following implant placement. The treatment trajectory and the
costs can thus be significantly reduced whilst the patient gets to enjoy the
implant-supported dentures sooner.
PMID- 28501880
TI - [Preventive dentistry 5. Secondary caries].
AB - Secondary caries is reported as one of the most important reasons for replacing
restorations. The patient's general caries risk plays an important role in the
development of secondary caries. The connection, at the patient level, between
various factors, the risk of caries and restoration factors, such as the presence
of a gap and the kind of restoration material, deserves additional investigation.
The minimum gap width in which secondary caries can develop is most likely less
than 100 um and could depend on the patient's caries risk. Composite restorations
seem more susceptible to secondary caries than amalgam restorations in patients
with high caries risk. So far, there is no unambiguous explanation for this
difference. The prevention of secondary caries is comparable to that of primary
caries and stresses the importance of fluoride, diet and oral hygiene.
PMID- 28501881
TI - [Medicaments and oral healthcare 4. Pharmacotherapy in (frail and care dependent)
older people].
AB - Polypharmacy is the consequence of multimorbidity. Both phenomena may cause
functional limitations and/or frailty and/or care dependency in older people. In
the human body, a medicament undergoes at least 3 important actions: absorption,
distribution and elimination. These actions may proceed aberrantly in older
people. Following interaction with receptors, a medicament triggers a chain
reaction in the human body. The receptors and each link of the chain reaction may
be subject to changes due to diseases as well as ageing. This, particularly, is
the case with regard to medications directed towards the central nervous system
and the cardiovascular system. Furthermore, interactions may occur between
various medications mutually and between medications on the one hand and on the
other hand food and water intake, self-medication with herbs, and diseases.
Moreover, older people usually experience more adverse effects of medications
when compared to younger people. This is due to altered body actions and
reactions, polypharmacy and the many possible interactions. In older people,
utilisation and intake of medications often give rise to problems that can be
divided into medicament-related, patient-related, care- and care provider-related
and other problems.
PMID- 28501882
TI - [Caries in deprived areas 2. Youngsters].
AB - In the Netherlands, no epidemiologic data on the oral health of cultural groups
of children and adolescents living in deprived areas are available. The aim of
the present study was to obtain an impression of the amount of caries experience
among poorly educated groups of youngsters in deprived areas, in comparison with
a reference group of poorly educated youngsters from the cities of Alphen aan den
Rijn, Gouda, 's-Hertogenbosch and Breda. 725 Poorly educated respondents
participated in a clinical and sociological study. The reference group had the
lowest caries experience and the youngsters living in deprived areas with a non
Dutch cultural affiliation had the largest amount of caries experience. The
latter group had more untreated caries and in 20-year-olds, a relatively large
number of teeth had been extracted. Despite the low numbers, the difference in
average DMFS scores among 14- and 20-year-olds were statistically significant. In
the Netherlands a cultural dichotomy in oral health appears to exist, independent
of level of education, in which youngsters with a non-Dutch cultural background
are at a disadvantage.
PMID- 28501883
TI - [A PhD completed 9. The value of oral foci screening in oncology patients].
AB - In both patients who undergo radiotherapy because of a tumour in the head and
neck region and patients who are treated with high doses of chemotherapy because
of haematological disorders, prior to treatment an oral foci screening is carried
out. The aim of this focus investigation is to identify oral abnormalities, the
so-called oral foci. Such foci can lead to oral problems during or post
treatment. A careful oral foci screening, conforming to protocol, appears to be
very relevant for patients who have to undergo head and neck radiotherapy.
Particular attention must be devoted to the evaluation of the perodontium,
because the chance of disorders affecting the bone-healing that appear post
radiotherapy in the head and neck region is increased in patients with
periodontitis. In patients with a haematological disorder, asymptomatic, chronic
foci do not require treatment prior to or during the oncological treatment
because such oral foci do not increase an extra risk of infectious complications,
despite what was hitherto believed.
PMID- 28501884
TI - The effect of systemic treatments on periostin expression reflects their
interference with the eosinophilic inflammation in chronic rhinosinusitis with
nasal polyps.
AB - BACKGROUND: Periostin is a recently discovered biomarker for eosinophilic
inflammation. Chronic rhinosinusitis with nasal polyps is a T-helper 2-skewed
chronic inflammatory airway disease. Medical treatments aim to relieve symptoms
and maintain clinical control by interfering with the inflammatory cascade. The
effect on nasal and serum periostin levels is however yet unknown. We aimed to
evaluate the effect of omalizumab, mepolizumab, methylprednisolone and
doxycycline on nasal and systemic periostin expression. METHODS: This study is
based on 3 previously published trials. Nasal and systemic periostin were
assessed in CRSwNP patients, randomly assigned to receive doxycycline (n=14),
methylprednisolone (n=14), mepolizumab (n=20) or omalizumab (n=15). There was a
control group for each treatment scheme. Doxycycline (200 mg on the first day,
followed by 100 mg once daily) and methylprednisolone (32-8 mg once daily) were
administered during 20 days; mepolizumab was injected at baseline and at 4 weeks.
Omalizumab was injected every 2 or 4 weeks, following the official drug leaflet.
RESULTS: Methylprednisolone and omalizumab significantly reduced serum periostin
levels at 4 and 8 weeks, respectively, after the start of the treatment. The
effect of methylprednisolone was transient. Nasal periostin levels decreased
significantly after 8 weeks of treatment with mepolizumab. The periostin
expression is in accordance with the previously reported effect on the
eosinophilic inflammation and clinical outcome. CONCLUSION: All treatment options
distinctly influence periostin expression, reflecting the interference with the
local or systemic eosinophilic inflammatory cascade.
PMID- 28501886
TI - Rhinophototherapy in chronic rhinosinusitis: a double blind randomized placebo
controlled trial.
AB - BACKGROUND: This study evaluated the efficacy of rhinophototherapy in patients
with chronic rhinosinusitis (CRS) without nasal polyps. METHOD: In this
randomized double-blind, placebo-controlled trial, CRS patients (n=50) received
either mixed visible and ultraviolet (UVA and UVB) light source application
(mUV/VIS) or visible light alone that served as placebo. Both groups were treated
for 3 weeks. RESULTS: Results in the rhinophototherapy and placebo group were not
significantly different and failed to reduce patient-reported outcomes measures
(Rhinosinusits Disability Index, Visual Analogic Scale of symptom severity) and
objective scores (rhinomanometry, olfactory thresholds, nasal Nitic Oxide
concentrations), immediately and one month after treatment. CONCLUSIONS: The
present data suggest that rhinophototherapy is not an efficient treatment for
chronic rhinosinusitis without nasal polyps.
PMID- 28501885
TI - EUFOREA Rhinology Research Forum 2016: report of the brainstorming sessions on
needs and priorities in rhinitis and rhinosinusitis.
AB - The first European Rhinology Research Forum organized by the European Forum for
Research and Education in Allergy and Airway Diseases (EUFOREA) was held in the
Royal Academy of Medicine in Brussels on 17th and 18th November 2016, in
collaboration with the European Rhinologic Society (ERS) and the Global Allergy
and Asthma European Network (GA2LEN). One hundred and thirty participants
(medical doctors from different specialties, researchers, as well as patients and
industry representatives) from 27 countries took part in the multiple perspective
discussions including brainstorming sessions on care pathways and research needs
in rhinitis and rhinosinusitis. The debates started with an overview of the
current state of the art, including weaknesses and strengths of the current
practices, followed by the identification of essential research needs, thoroughly
integrated in the context of Precision Medicine (PM), with personalized care,
prediction of success of treatment, participation of the patient and prevention
of disease as key principles for improving current clinical practices. This
report provides a concise summary of the outcomes of the brainstorming sessions
of the European Rhinology Research Forum 2016.
PMID- 28501891
TI - Dual-energy X-ray absorptiometry and fracture prediction in patients with spinal
cord injuries and disorders: methodological issues.
PMID- 28501890
TI - The role of adipokines as prognostic factors of one-year mortality in hip
fracture patients.
AB - : This study investigated the impact of anthropometric parameters, adiponectin,
leptin, homeostatic model assessment for insulin resistance (HOMA-IR), beta
isomerised C-terminal telopeptide of collagen type I (beta-CTX), and routine
biochemical tests on one-year mortality in hip fracture patients. We found that
male patients with high adiponectin, leptin, and beta-CTX levels had a 5-fold
increase in all-cause one-year mortality. INTRODUCTION: Several predictors of one
year hip fracture mortality have been identified including advanced age, male
sex, low bone mineral density, and preexisting comorbidities. However, the impact
of metabolic parameters on hip fracture mortality remains unknown. The aim of
this study was to examine the effect of serum leptin and adiponectin levels, as
well as other metabolic parameters on all-cause one-year hip fracture mortality.
METHODS: This prospective study included 236 patients of all ages with non
traumatic hip fractures. Anthropometric parameters, adiponectin, leptin, HOMA-IR,
beta-CTX, and routine biochemical tests were recorded at admission and correlated
with one-year mortality by using multivariate Cox proportional hazard models.
RESULTS: The median patient age was 82 (75-87) years, and one-year mortality rate
was 28.4%. In univariate analysis, adiponectin, age, beta-CTX, and renal function
were associated with mortality. However, in a multivariate model, male gender,
high beta-CTX, adiponectin, and leptin were independently associated with
increased mortality. Thus, we constructed a nomogram that included all the latter
variables in addition to age. The nomogram predicted mortality with a sensitivity
of 74.8% (66.0-82.3) and specificity of 74.4% (57.9-87.0), and had an area under
the curve of 0.784. Patients that scored <9.2 had a mortality of 10.1%, while
those with >9.2 had a mortality of 49.2% (relative risk 5.4, 95% CI 2.8-10.2, P <
0.001). CONCLUSION: Male patients with high adiponectin, leptin, and beta-CTX
levels have a 5-fold increase in all-cause one-year mortality after hip fracture.
PMID- 28501892
TI - A New Primer to Amplify pmoA Gene From NC10 Bacteria in the Sediments of
Dongchang Lake and Dongping Lake.
AB - Nitrite-dependent anaerobic methane oxidation (n-damo) is catalyzed by the NC10
phylum bacterium "Candidatus Methylomirabilis oxyfera" (M. oxyfera). Generally,
the pmoA gene is applied as a functional marker to test and identify NC10-like
bacteria. However, it is difficult to detect the NC10 bacteria from sediments of
freshwater lake (Dongchang Lake and Dongping Lake) with the previous pmoA gene
primer sets. In this work, a new primer cmo208 was designed and used to amplify
pmoA gene of NC10-like bacteria. A newly nested PCR approach was performed using
the new primer cmo208 and the previous primers cmo182, cmo682, and cmo568 to
detect the NC10 bacteria. The obtained pmoA gene sequences exhibited 85-92%
nucleotide identity and 95-97% amino acid sequence identity to pmoA gene of M.
oxyfera. The obtained diversity of pmoA gene sequences coincided well with the
diversity of 16S rRNA sequences. These results indicated that the newly designed
pmoA primer cmo208 could give one more option to detect NC10 bacteria from
different environmental samples.
PMID- 28501893
TI - HSPB8 haploinsufficiency causes dominant adult-onset axial and distal myopathy.
PMID- 28501895
TI - Angiogenesis is VEGF-independent in the aged striatum of male rats exposed to
acute hypoxia.
AB - Brain hypoxia is involved in many diseases. The activation of angiogenesis is one
of the major adaptive mechanisms to counteract the adverse effects of hypoxia. In
a previous work, we have shown that the adult rat striatum promotes angiogenesis
in response to hypoxia via upregulation of the most important proangiogenic
factor, the vascular endothelial growth factor (VEGF). However, the effects of
hypoxia on angiogenesis in the aged striatum remain unknown and constitute our
aim. Here we show the upregulation of hypoxia-inducible factor-1alpha in the
striatum of aged (24-25 months old) Wistar rats exposed to acute hypoxia and
analysed during a reoxygenation period ranging from 0 h to 5 days. While the mRNA
expression of the proangiogenic factors VEGF, transforming growth factor-beta1
(TGF-beta1), and adrenomedullin dropped at 0 h post-hypoxia compared to normoxic
control, no changes were detected at the protein level, showing an impaired
response of these proangiogenic factors to hypoxia in the aged striatum. However,
the striatal blood vessel network increased at 24 h of reoxygenation, suggesting
that mechanisms independent from these proangiogenic factors may be involved in
hypoxia-induced angiogenesis in the striatum of aged rats. A thorough
understanding of the factors involved in the response to hypoxia is essential to
guide the design of therapies for hypoxia-related diseases in the aged brain.
PMID- 28501894
TI - Influence of ageing on the microarchitecture of the spleen and lymph nodes.
AB - The elderly have a decreased response to vaccination and an increased
susceptibility to infectious diseases. The spleen and lymph nodes are important
secondary lymphoid organs where immune cells can rapidly respond to pathogenic
material in the blood and lymph in order to mount long-term adaptive immune
responses to those pathogens. In aged mice and humans structural changes occur to
both the spleen and lymph nodes. These structural changes affect the functioning
of the immune cells within, which may ultimate result in less effective or
decreased immune responses. This review describes our current understanding of
the structural changes that occur to the spleen and lymph nodes of elderly mice.
However, where data are available, we also discuss whether similar changes occur
in tissues from elderly humans. A particular focus is made on how these
structural changes are considered to impact on the functioning of the immune
cells within. The world's population is currently living longer than ever before.
The increased incidence and severity of infectious diseases in the elderly has
the potential to have a significant impact on the health care system if solutions
are not identified. A thorough understanding of the molecular causes of these
ageing-related structural changes to the spleen and lymph nodes may help to
identify novel treatments that could repair them, and in doing so, improve immune
responses and vaccine efficacy in the elderly.
PMID- 28501896
TI - What do Biologists Make of the Species Problem?
AB - The concept of species is one of the core concepts in biology and one of the
cornerstones of evolutionary biology, yet it is rife with conceptual problems.
Philosophers of biology have been discussing the concept of species for decades,
and in doing so they sometimes appeal to the views of biologists. However, their
statements as to what biologists think are seldom supported by empirical data. In
order to investigate what biologists actually think about the key issues related
to the problem of species, we have conducted a survey on the sample of 193
biologists from the population of biologists from over 150 biology departments at
universities in the US and the EU. This article presents and discusses the
results of the survey. Some results confirm and others falsify the reiterated
statements of philosophers of biology as to what biologists think, but all
results we obtained should be informative and relevant for future discussions of
the problem of species.
PMID- 28501897
TI - MiR-181b modulates chemosensitivity of glioblastoma multiforme cells to
temozolomide by targeting the epidermal growth factor receptor.
AB - Temozolomide (TMZ) is a promising chemotherapeutic agent to treat Glioblastoma
multiforme (GBM). However, resistance to TMZ develops quickly with a high
frequency. The mechanisms underlying GBM cells' resistance to TMZ are not fully
understood. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate
protein expression by cleaving or repressing the translation of target mRNAs.
Recently, miRNAs have been discovered to play important roles in drug resistance.
A previous study showed that miR-181b in involved in glioma tumorigenesis. Thus,
it would be valuable to explore the functions and mechanisms of miR-181b in
regulating GMB cells' sensitivity to TMZ. In this study, quantitative real-time
reverse transcription PCR (qRT-PCR) data indicated that miR-181b was
significantly downregulated in recurrent GBM tissues compared with initial GBM
tissues. We also found that miR-181b overexpression increased the chemo
sensitivity of GBM cells to TMZ and potentiated TMZ-induced apoptosis in vitro
and in vivo. Moreover, we demonstrated that the epidermal growth factor receptor
(EGFR) was a direct target of miR-181b: restoration of EGFR rescued the
inhibitory effects of miR-181b and TMZ treatment. Taken together, our data
support strongly an important role for miR-181b in conferring TMZ resistance by
targeting EGFR expression.
PMID- 28501898
TI - Family First? The Costs and Benefits of Family Centrality for Adolescents with
High-Conflict Families.
AB - Youth who do not identify with or value their families (i.e., low family
centrality) are considered to be at risk for maladjustment. However, the current
study investigated whether low family centrality may be adaptive in negative
family contexts (i.e., high family conflict) because youth's self-worth should be
less tied to the quality of their family relationships. Multilevel models using
daily diaries and latent variable interactions using longitudinal questionnaires
indicated that, among a sample of 428 Mexican American adolescents (49.8% male, M
age = 15.02 years), lower family centrality was generally detrimental to youth's
well-being. However, for youth in adverse family environments, low family
centrality ceased to function as a risk factor. The present findings suggest that
family centrality values play a more nuanced role in youth well-being than
previously believed, such that low family centrality may be an adaptive response
to significant family challenges.
PMID- 28501899
TI - Is there a "July effect" in pediatric neurosurgery?
AB - PURPOSE: The belief that July, when resident physicians' training year begins,
may be associated with increased risk of patient morbidity and mortality is known
as the "July effect." This study aimed to compare complication rates after
pediatric neurosurgical procedures in the first versus last academic quarters in
two national datasets. METHODS: Data were extracted from the National Surgical
Quality Improvement Program-Pediatrics (NSQIP-P) database for year 2012 for 30
day complication events and the Kids' Inpatient Database (KID) for year 2012 for
in-hospital complication events after pediatric neurosurgical procedures.
Descriptive and analytic statistical methods were used to characterize the impact
of seasonal variation between the first and last quarters on complications.
RESULTS: Three thousand six hundred twenty-four procedures in the NSQIP-P dataset
and 14,855 hospitalizations in KID were included in the study cohort. No
significant difference was observed between the first and fourth quarters for
these complication events: wound disruption/dehiscence, wound infection, nerve
injury, bleeding requiring transfusion, central line-associated BSI, deep venous
thrombosis/pulmonary embolism, urinary tract infection, renal failure, re
intubation/pulmonary failure, cardiac arrest, stroke, coma, and death. There was
no difference in the average length of stay or average length of surgical time.
In the NSQIP-P, the first quarter was associated with a significantly increased
incidence of pneumonia and unplanned re-operation; there was a trend towards
increased incidence of unplanned re-admission and sepsis. In KID, there was no
difference in the rate of pneumonia or sepsis. CONCLUSION: For the majority of
morbidity and mortality events, no significant difference was found in occurrence
rates between the first and last quarters.
PMID- 28501900
TI - Autonomic nervous system in newborns: a review based on heart rate variability.
AB - PURPOSE: Heart rate variability (HRV) has been a relevant tool in the assessment
of the autonomic nervous system (ANS). How autonomic control normally develops in
newborns and how it is affected by gestational age (GA) is not fully understood.
We aimed to review the current evidence on HRV in preterm (PT) and term neonates
(TN) and investigate the relation between GA and the maturation of ANS. METHODS:
Electronic databases (Pubmed, World of Science, and Scopus) were searched for
studies from 1997 to 2017 examining HRV (time and frequency domain) in PT and TN
who followed to the Task Force (1996) guidelines. Ten studies met our inclusion
criteria and were analyzed. RESULTS: An increasing postnatal age was related to a
significant rise of HRV parameters. Several significant differences were
established between PT and TN (lower values on PTN), also found when PTN are
evaluated at their theoretical term age. In general, there were no relevant
results on LF/HF (low frequency/high frequency) ratio, as being an adequate
marker of sympathovagal balance, but this was not a universal finding of this
review. Frequency parameters that were more often used to evaluate newborns and
HF showed the most relevant increase with GA. CONCLUSIONS: HRV is an important
tool to assess the maturation of ANS in newborns and there is a progressive
increasing on cardiac parasympathetic activity, according to GA. HF appears as a
relevant parameter in measurements of vagal maturation. HRV is higher in TN when
compared with PTN and is more studied in newborns in terms of frequency domain.
Standard recommendations in newborns remain to be fully defined.
PMID- 28501901
TI - Production of Mycosporine-Like Amino Acids from Gracilaria vermiculophylla
(Rhodophyta) Cultured Through One Year in an Integrated Multi-trophic Aquaculture
(IMTA) System.
AB - This study evaluates the production of biomass and mycosporine-like amino acids
(MAAs) throughout the year in Gracilaria vermiculophylla (Rhodophyta) collected
in Ria de Aveiro (Portugal). The algae were grown in outdoor tanks in seawater
with the addition of fishpond effluents under two different water flows (100 and
200 L h-1) in an integrated multi-trophic aquaculture (IMTA) system (tanks 1200
L; 1.5 m2) and different algal densities (3, 5, and 7 kg m-2). MAA content in
IMTA seaweeds was significantly affected by the interaction of time and stocking
density, but not by the water flow. The highest MAA content was observed in April
(about 3.13 mg g-1 DW) followed by May (1.79 mg g-1 DW). Seaweed biomass
productivity was higher in May (372.06 g DW m-2 week-1) than in April (353.40 g
DW m-2 week-1). Four MAAs were identified by HPLC and electrospray ionization
mass spectrometry (ESI-MS) in G. vermiculophylla: Porphyra-334, Shinorine,
Palythine and Asterina-330. The highest levels of Porphyra-334 and Shinorine were
reached from November to January and the Palythine + Asterina-330 from April to
August. Taking into account the average biomass and MAA production of G.
vermiculophylla growing in this IMTA system (8.56 g of MAA in 18 m2 culture along
8 months; 35.5% produced in April), a total amount of 71.33 g MAA year-1 could be
produced in this system by scaling up to 100 m2. MAAs could be further used as
photoprotector and antioxidant compounds in cosmetic products.
PMID- 28501902
TI - A new 4-Amino-7-Nitro-2,1,3-Benzoxadiazole (ANBD)-Based Fluorescent Probe for the
Detection of Hg2.
AB - Based on the photoinduced electron transfer (PET) principle, 4-amino-7-nitro
2,1,3-benzoxadiazole (ANBD) has been used as a fluorophore to develop a new
fluorescent probe, 4-(2-N,N-dimethylthioacetamide)amino-7-nitro-2,1,3
benzoxadiazole (2), for the detection of Hg2+. Upon the addition of Hg2+, a 46
fold fluorescence enhancement occurs. Moreover the probe 2 exhibits a high
selectivity and sensitivity to Hg2+, even in the presence of other common metal
ions. Under optimal reaction conditions, a good linearity can be obtained in the
range of 0.5-2.5 MUM, and the detection limit is 0.05 MUM. In addition, the
desulfurization reaction mechanism is proposed based on electrospray ionization
mass spectrum. The present study is not only a supplement to the detection method
of Hg2+, but also a merit to the development of ANBD-based fluorescent probes.
PMID- 28501903
TI - Coumarin-Pyrazole Hybrid with Red Shifted ESIPT Emission and AIE Characteristics
a Comprehensive Study.
AB - The newly synthesized three coumarin pyrazole hybrid excited state intramolecular
proton transfer (ESIPT) dyes show efficient charge transfer from the pyrazole
ring and the coumarin towards the electron withdrawing dicyanovinylene group as
revealed from the frontier molecular orbitals. Aggregation induced emission
enhancement (AIEE) studies with 2-((3-(4-hydroxy-2-oxo-2H-chromen-3-yl)-1-phenyl
1H-pyrazol-4-yl)methylene) malononitrile showed 9 fold increase in the emission
enhancement in 90% DMF-H2O mixture. Lippert-Mataga theory explained the
solvatochromic behavior of the dyes in various solvents. The charge transfer
characteristics and non-linear optical (NLO) properties have been supported and
correlated with bond length alternation, bond order alternation and vibrational
spectrum. As values of bond order alternation (BOA) tend to be more towards
negative and as the value of alpha increases beta decreases while the values of
gamma depends on the values of alpha and beta. The observed values of gamma are
positive which revealed that beta contributes significantly. The dyes exhibit
linear and NLO properties superior to urea. (E)-2-(3-(2-(3-(4-Hydroxy-2-oxo-2H
chromen-3-yl)-1-phenyl-1H-pyrazol-4-yl)vinyl)-5,5-dimethylcyclohex-2-en-1
ylidene) malononitrile shows enhanced linear and non-linear properties among the
three dyes.
PMID- 28501904
TI - Relationship Between Perisylvian Essential Language Sites and Arcuate Fasciculus
in the Left Hemisphere of Healthy Adults.
AB - Essential language sites and the arcuate fasciculus (AF) have been extensively
researched. However, the relationship between them remains insufficiently
studied, especially in healthy people. Navigated transcranial magnetic
stimulation (nTMS) is increasingly used in language mapping. While enjoying the
advantage of non-invasiveness, it is also capable of inducing a virtual lesion in
the brain. Thus, it offers the possibility of using the virtual-lesion method to
study the healthy brain. This study combined nTMS and diffusion tensor imaging
(DTI) tractography to investigate the relationship between essential language
sites and the AF in 30 healthy right-handed volunteers. A total of 143 essential
language sites were identified using nTMS, and a total of 175 AF terminations
were identified using DTI tractography. Sixty-six sites had a direct correlation
with the AF, accounting for 46% of the total essential language sites. Forty
seven AF terminations harbored essential language sites, accounting for 27% of
the total AF terminations. Upon data rendering to the cortical parcellation
system, a region-related heterogeneity of the correlation rate was found. This
study provides the first data on the relationship between essential language
sites and the AF in healthy adults.
PMID- 28501905
TI - Investigation of Pain Mechanisms by Calcium Imaging Approaches.
AB - Due to the complex circuitry and plethora of cell types involved in
somatosensation, it is becoming increasingly important to be able to observe
cellular activity at the population level. In addition, since cells rely on an
intricate variety of extracellular factors, it is important to strive to maintain
the physiological environment. Many electrophysiological techniques require the
implementation of artificially-produced physiological environments and it can be
difficult to assess the activity of many cells simultaneously. Moreover, imaging
Ca2+ transients using Ca2+-sensitive dyes often requires in vitro preparations or
in vivo injections, which can lead to variable expression levels. With the
development of more sensitive genetically-encoded Ca2+ indicators (GECIs) it is
now possible to observe changes in Ca2+ transients in large populations of cells
at the same time. Recently, groups have used a GECI called GCaMP to address
fundamental questions in somatosensation. Researchers can now induce GCaMP
expression in the mouse genome using viral or gene knock-in approaches and
observe the activity of populations of cells in the pain pathway such as dorsal
root ganglia (DRG), spinal neurons, or glia. This approach can be used in vivo
and thus maintains the organism's biological integrity. The implementation of
GCaMP imaging has led to many advances in our understanding of somatosensation.
Here, we review the current findings in pain research using GCaMP imaging as well
as discussing potential methodological considerations.
PMID- 28501907
TI - Tacit knowledge.
AB - Information that is not made explicit is nonetheless embedded in most of our
standard procedures. In its simplest form, embedded information may take the form
of prior knowledge held by the researcher and presumed to be agreed to by
consumers of the research product. More interesting are the settings in which the
prior information is held unconsciously by both researcher and reader, or when
the very form of an "effective procedure" incorporates its creator's (unspoken)
understanding of a problem. While it may not be productive to exhaustively detail
the embedded or tacit knowledge that manifests itself in creative scientific
work, at least at the beginning, we may want to routinize methods for extracting
and documenting the ways of thinking that make "experts" expert. We should not
back away from both expecting and respecting the tacit knowledge the pervades our
work and the work of others.
PMID- 28501906
TI - Medication use for the treatment of diabetes in obese individuals.
AB - Obesity is a major cause of type 2 diabetes and may complicate type 1 diabetes.
Weight loss for obese individuals with diabetes has many health benefits, often
leads to improvement in glucose control and sometimes, in type 2 diabetes, near
normalisation of abnormal glucose metabolism. Weight loss is difficult to
maintain and attempts to lose weight may be undermined by some diabetes
treatments such as sulfonylureas, thiazolidinediones and insulin. Whilst
lifestyle support should be the primary approach to aid individuals who wish to
lose weight, pharmacological approaches can also be considered. These include
choosing glucose-lowering drugs or drug combinations that are weight neutral or
result in weight loss or prescribing drugs that are specifically approved as anti
obesity medication. Given that some of the newer glucose-lowering medications
that cause weight loss, such as glucagon-like peptide-1 receptor agonists (GLP-1
RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i), are also being used
or considered for use as anti-obesity drugs, it seems that the distinction
between glucose-lowering medication and weight loss medication is becoming
blurred. This review discusses the main pharmacological approaches that can be
used to support weight loss in individuals with diabetes.
PMID- 28501908
TI - A tale of three cuffs: the hemodynamics of blood flow restriction.
AB - INTRODUCTION: The blood flow response to relative levels of blood flow
restriction (BFR) across varying cuff widths is not well documented. With the
variety of cuff widths and pressures reported in the literature, the effects of
different cuffs and pressures on blood flow require investigation. PURPOSE: To
measure blood pressure using three commonly used BFR cuffs, examine possible
venous/arterial restriction pressures, and measure hemodynamic responses to
relative levels of BFR using these same cuffs. METHODS: 43 participants
(Experiment 1, brachial artery blood pressure assessed) and 38 participants
(Experiment 2, brachial artery blood flow assessed using ultrasound, cuff placed
at proximal portion of arm) volunteered for this study. RESULTS: Blood pressure
measurement was higher in the 5 cm cuff than in the 10 and 12 cm cuffs. Sub
diastolic relative pressures appear to occur predominantly at <60% of arterial
occlusion pressure (AOP). Blood flow under relative levels of restriction
decreases in a non-linear fashion, with minimal differences between cuffs
[resting: 50.3 (44.2) ml min-1; 10% AOP: 42.0 (36.8); 20%: 33.6 (28.6); 30%: 23.6
(20.4); 40%: 17.1 (15.9); 50%: 12.5 (9.4); 60%: 11.5 (8.1); 70%: 11.4 (7.0); 80%:
10.3 (6.3); 90%: 7.9 (4.8); 100%: 1.5 (2.9)]. Peak blood velocity remains
relatively constant until higher levels (>70% of AOP) are surpassed. Calculated
mean shear rate decreases in a similar fashion as blood flow. CONCLUSIONS: Under
relative levels of restriction, pressures from 40 to 90% of AOP appear to
decrease blood flow to a similar degree in these three cuffs. Relative pressures
appear to elicit a similar blood flow stimulus when accounting for cuff width and
participant characteristics.
PMID- 28501909
TI - Vitamin K antagonist therapy: changes in the treated populations and in
management results in Italian anticoagulation clinics compared with those
recorded 20 years ago.
AB - Vitamin K antagonists (VKA) are the most widely used anticoagulants in the world.
An appropriate management of treated patients is crucial for their efficacy and
safety. The prospective, observational, multicenter, inception-cohort FCSA-START
Register, a branch of START Register (NCT02219984) included VKA-treated patients
managed by centers of Italian Federation of anticoagulation clinics (AC).
Baseline patient characteristics and data during treatment were analyzed and
compared with those of ISCOAT study, performed by the Federation and published in
1996/7. 5707 naive patients [53% males, mean age 73.0 years (28.1% >80 years)],
61.6% treated for atrial fibrillation (AF), and 28.0% for venous thromboembolism
were included. During the 8906 patient-years (pt-yrs) of observation, 123
patients had major bleeding (MB) (1.38% pt-yrs; fatal: 0.11% pt-yrs), while non
major clinically relevant bleeds were 144 (1.62% pt-yrs). Bleeding was more
frequent in elderly (>=70 years; p = 0.04), and during initial 3-month therapy (p
= 0.02). Bleeding rate was 2.5% pt-yrs for temporally related INR results <3.0,
increasing to 12.5% for INR >= 4.5. Thrombotic events were 47 (0.53% pt-yrs; 4
fatal 0.04% pt-yrs). Compared with ISCOAT-1996/7 results, patients older than 80
y are increased from 8 to 28% (p < 0.01), and those treated for AF are increased
from 17 to 61%. The quality of anticoagulation control and incidence of MB are
not different. However, thrombotic complications fell drastically from 3.5 to
0.53% pt-yrs (p < 0.01), with lower mortality (p = 0.01). VKA-treated patients
monitored in Italian AC have good clinical results, with low bleeding and
thrombotic complications rates. Important changes in the treated population and
improvement in thrombotic complications are detected compared with the ISCOAT
1996/7 study.
PMID- 28501911
TI - Analysis of circumflex artery anatomy by real time 3D transesophageal
echocardiography compared to cardiac computed tomography.
AB - Iatrogenic injury to the circumflex artery (Cx) due to its close proximity to the
mitral annulus is a rare but dreadful complication that can occur during mitral
valve repair. The aim of our study was to compare multiple measurements of the Cx
datasets, obtained by real time three-dimensional transesophageal
echocardiography (RT3D TEE) and corresponding measurements assessed in multi
planar three-dimensional images acquired by multidetector computed tomography
(MDCT). Preoperative RT3D TEE and MDCT datasets of 25 patients who had previously
undergone minimally invasive mitral valve surgery were retrospectively analyzed.
The vessel diameter and the horizontal as well as vertical distances from the
center of the Cx to the mitral valve annulus were measured. Horizontal as well as
vertical Cx distances showed a strong correlation between measurements of RT3D
TEE and MDCT whereas the measurements of the Cx diameter showed no correlation.
Measurements of horizontal and vertical distances of the Cx to the mitral annulus
can be performed using RT3D TEE and show good correlation with MDCT-based
measurements.
PMID- 28501913
TI - Chronic Myeloid Leukemia: Immunobiology and Novel Immunotherapeutic Approaches.
AB - Imatinib has revolutionized the treatment and prognosis of chronic myeloid
leukemia (CML) with survival rates now approaching those of the age-matched
healthy population. To be able to discontinue tyrosine kinase inhibitor (TKI)
treatment, it is necessary to develop complementary therapies to target minimal
residual disease. Recent findings by a number of investigators in both CML mouse
models and CML patients offer evidence that many factors in the leukemic
microenvironment can collectively contribute to immune escape, including
expansion of myeloid-derived suppressor cells, programmed death-1/programmed
death-1 ligand interactions resulting in T-cell impairment, expression of soluble
suppressive factors such as soluble CD25, and down-regulation of MHC molecules by
CML cells. Other investigators have studied the role of cytokines on the
resistance to TKIs by leukemic stem cells (LSCs) and have highlighted the
implication of the JAK/STAT pathway as well as the interleukin 1 (IL-1) signaling
pathway. Distinct immunologic strategies have been considered to harness the
immune system or trigger LSC death to allow more CML patients to discontinue TKI
treatment (so-called functional cure). Successful immunotherapy and TKI
combination and the optimal timing of immunotherapy determination represent major
challenges for the future.
PMID- 28501912
TI - Idiopathic retroperitoneal fibrosis: clinical features and long-term renal
function outcome.
AB - PURPOSE: To evaluate the long-term renal function outcome of management of
retroperitoneal fibrosis (RPF)-induced ureteral obstruction. METHODS: Thirty-six
patients with idiopathic RPF-induced ureteral obstruction were classified
according to the management type into two groups, group A; managed by indwelling
JJ stent and group B managed by ureterolysis and omental wrapping (UOR). The
primary outcome was to define the long-term outcome of management on RF. It was
evaluated by changes in serum creatinine and estimated GFR (eGFR) using
Modification of Diet in Renal Disease equation where 20% changes in eGFR is
considered significant. The second outcome is to compare the outcomes between
both groups. RESULTS: After 27.5 (1-124) months, median (range) follow-up, median
(range) serum creatinine increased significantly from 1.5 (0.8-8.1) to 1.6 (1
12.1) mg/dl (p value =0.04) and eGFR showed non-statistical significant reduction
from 43 (5-110) to 41 (5-88) ml/min/1.73 m2 (p value =0.3). Eight (22.2%), 12
(34.4%) and 16 (44.4%) patients showed stable, increased and decreased eGFR.
Group A showed statistically significant increased serum creatinine and
insignificant decreased eGFR (p value =0.04 and 0.09), while group B showed
statistically insignificant changes in serum creatinine and eGFR (p value =0.5
and 0.9). In group B, nine (21.4%) renal units are still harboring JJ stents.
CONCLUSION: For idiopathic RPF, UOR avoided indwelling ureteral stents in 78.6%
of renal units with apparent better long-term renal function outcome.
PMID- 28501910
TI - Targeting the dominant mechanism of coronary microvascular dysfunction with
intracoronary physiology tests.
AB - The coronary microcirculation plays a key role in modulating blood supply to the
myocardium. Several factors like myocardial oxygen demands, endothelial and
neurogenic conditions determine its function. Although there is available
evidence supporting microvascular dysfunction as an important cause of myocardial
ischaemia, with both prognostic and symptomatic implications, its diagnosis and
management in clinical practice is still relegated to a second plane. Both
diagnostic and therapeutic approaches are hampered by the broadness of the
concept of microvascular dysfunction, which fails addressing the plurality of
mechanisms leading to dysfunction. Normal microcirculatory function requires both
structural integrity of the microcirculatory vascular network and preserved
signalling pathways ensuring adequate and brisk arteriolar resistance shifts in
response to myocardial oxygen demands. Pathological mechanisms affecting these
requirements include structural remodelling of microvessels, intraluminal
plugging, extravascular compression or vasomotor dysregulation. Importantly, not
every diagnostic technique provides evidence on which of these pathophysiological
mechanisms is present or predominates in the microcirculation. In this paper we
discuss the mechanisms of coronary microvascular dysfunction and the
intracoronary tools currently available to detect it, as well as the potential
role of each one to unmask the main underlying mechanism.
PMID- 28501914
TI - Skermanella mucosa sp. nov., isolated from crude oil contaminated soil.
AB - A novel Gram-stain negative, small rod-shaped bacterium (strain 8-14-6T) was
isolated from hydrocarbon contaminated desert soil collected from Kuwait. Strain
8-14-6T grew at 5-37 degrees C, pH 6.0-8.8 and 0-2% (w/v) of NaCl concentration.
Casein, starch, Tween 20 and Tween 80 were hydrolyzed while urea, chitin, DNA and
carboxymethyl-cellulose were not hydrolyzed by strain 8-14-6T. The major cellular
fatty acids were identified as C18:1omega6c/C18:1omega7c, C16:0 and iso
C16:1I/C14:03-OH. Strain 8-14-6T produced diphosphatidylglycerol,
phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, an
unidentified phospholipids, two unidentified lipids and five unidentified amino
lipids as polar lipids. Genomic G+C content was 73.5 mol %. 16S rRNA gene
sequence comparisons indicated that strain 8-14-6T represents a member of the
genus Skermanella within family Rhodospirillaceae of the class
Alphaproteobacteria. Strain 8-14-6T has a sequence similarity of 98.9% with
Skermanella rosea M1T, 97.4% with Skermanella aerolata 5416T-32T, 96.9% with
Skermanella stibiiresistens SB22T and <95.4% with the other two known species of
the genus Skermanella. The DNA-DNA relatedness values between strain 8-14-6T and
the type strains of the closely related species were clearly below the 70%
threshold. From the combination of phenotypic and genotypic characteristics and
distinct phylogenetic position, the strain is considered to represent a novel
species of the genus Skermanella, for which the name Skermanella mucosa sp. nov.
is proposed. The type strain is 8-14-6T (=KEMB 2255-438T =JCM 31590T).
PMID- 28501915
TI - Role of the Inositol Polyphosphate Multikinase Ipk2 in Regulation of Hyphal
Development, Calcium Signaling and Secretion in Candida albicans.
AB - Inositol polyphosphates are a family of inositol derivatives and ubiquitously
distributed in various organisms. Their generation is catalyzed by inositol
polyphosphate multikinases, which play essential roles in abundant cellular
processes. However, little is known about the kinds and functions of inositol
polyphosphate multikinases in the important fungal pathogen, C. albicans. In this
study, we identified a C. albicans inositol polyphosphate multikinase, Ipk2. This
kinase shares the conserved IPK domain and localizes in the nucleus. A strain
with controllable expression of IPK2 was constructed using the inducible promoter
of MET3. Down-regulation of IPK2 by addition of methionine and cysteine enhanced
the ability of hyphal development, increased expression of hypha-specific genes
and promoted transport of hypha-specific factors. Moreover, this down-regulation
rendered increase in cytoplasmic calcium levels but decrease in cellular total
calcium contents, indicating its role in regulation of calcium homeostasis.
Assays of secretion and macrophage killing further demonstrated that Ipk2
negatively regulated secretion of degradative enzymes and damage to macrophages.
This study sheds a novel light on the functions of inositol polyphosphate
multikinases in fungal organisms.
PMID- 28501917
TI - A primer on systematic reviews in toxicology.
AB - Systematic reviews, pioneered in the clinical field, provide a transparent,
methodologically rigorous and reproducible means of summarizing the available
evidence on a precisely framed research question. Having matured to a well
established approach in many research fields, systematic reviews are receiving
increasing attention as a potential tool for answering toxicological questions.
In the larger framework of evidence-based toxicology, the advantages and
obstacles of, as well as the approaches for, adapting and adopting systematic
reviews to toxicology are still being explored. To provide the toxicology
community with a starting point for conducting or understanding systematic
reviews, we herein summarized available guidance documents from various fields of
application. We have elaborated on the systematic review process by breaking it
down into ten steps, starting with planning the project, framing the question,
and writing and publishing the protocol, and concluding with interpretation and
reporting. In addition, we have identified the specific methodological challenges
of toxicological questions and have summarized how these can be addressed.
Ultimately, this primer is intended to stimulate scientific discussions of the
identified issues to fuel the development of toxicology-specific methodology and
to encourage the application of systematic review methodology to toxicological
issues.
PMID- 28501918
TI - Exercise stress echocardiography in hypertrophic cardiomyopathy.
AB - In this review, we make a comprehensive summary of exercise stress
echocardiography in hypertrophic cardiomyopathy (HCM) and practical tips used in
our hospital. The main objective of performing exercise stress echocardiography
in patients with HCM is to evaluate left ventricular outflow tract obstruction,
mitral regurgitation, left ventricular asynergy, and diastolic function during
exercise. There are limitations to the explanations that can be provided for
exertional symptoms when resting echocardiography is performed in patients with
HCM. In contrast, exercise stress echocardiography causes the manifestation of
findings that are latent at rest, which possibly provides the elucidation of
symptom etiology. In this article, we focus on the usefulness of exercise stress
echocardiography in HCM.
PMID- 28501919
TI - Automated cytological detection of Barrett's neoplasia with infrared
spectroscopy.
AB - BACKGROUND: Development of a nonendoscopic test for Barrett's esophagus would
revolutionize population screening and surveillance for patients with Barrett's
esophagus. Swallowed cell collection devices have recently been developed to
obtain cytology brushings from the esophagus: automated detection of neoplasia in
such samples would enable large-scale screening and surveillance. METHODS:
Fourier transform infrared (FTIR) spectroscopy was used to develop an automated
tool for detection of Barrett's esophagus and Barrett's neoplasia in esophageal
cell samples. Cytology brushings were collected at endoscopy, cytospun onto
slides and FTIR images were measured. An automated cell recognition program was
developed to identify individual cells on the slide. RESULTS: Cytology review and
contemporaneous histology was used to inform a training dataset containing 141
cells from 17 patients. A classification model was constructed by principal
component analysis fed linear discriminant analysis, then tested by leave-one
sample-out cross validation. With application of this training model to whole
slide samples, a threshold voting system was used to classify samples according
to their constituent cells. Across the entire dataset of 115 FTIR maps from 66
patients, whole samples were classified with sensitivity and specificity
respectively as follows: normal squamous cells 79.0% and 81.1%, nondysplastic
Barrett's esophagus cells 31.3% and 100%, and neoplastic Barrett's esophagus
cells 83.3% and 62.7%. CONCLUSIONS: Analysis of esophageal cell samples can be
performed with FTIR spectroscopy with reasonable sensitivity for Barrett's
neoplasia, but with poor specificity with the current technique.
PMID- 28501920
TI - A dramatic blood plasticity in hibernating and 14-day hindlimb unloading Daurian
ground squirrels (Spermophilus dauricus).
AB - We compared the effects of hibernation inactivity and 14-day hindlimb unloading
in non-hibernating period on biochemical, rheological, and hematological
parameters of blood in Daurian ground squirrels (Spermophilus dauricus). Twenty
four squirrels were randomly divided into four groups: control (CON), hibernation
(HIB), post-hibernation (POST), and 14-day hindlimb unloading (HU). The results
showed that serum enzymes (L-lactate dehydrogenase, alanine aminotransferase, and
aspartate aminotransferase) activities decreased in HIB, POST, and HU squirrels
compared with CON. Total protein (including albumin and globulin) maintained in
HIB but decreased in HU compared with CON. Total cholesterol and high-density
lipoprotein-cholesterol increased in HIB but maintained in HU and POST compared
with CON. Meanwhile, serum creatinine decreased and urea increased in HU compared
with CON. All blood ions concentrations were unchanged in HIB, POST, and HU
squirrels compared with CON except calcium which increased in HIB compared with
CON, and phosphorus which increased in HIB and POST compared with CON. Most of
detected serum biochemical analytes in POST recovered to the CON level. Blood
viscosity, which was unchanged in all shear rates in HU, increased in HIB and
recovered in POST in lower shear rates compared with CON. Erythrocyte and
corpuscular volume decreased in HIB and HU but maintained in POST compared with
CON. All the routine hematological parameters recovered in POST as compared with
CON except platelet, which decreased in HIB and POST but maintained in HU
compared with CON. In conclusion, our results suggested a remarkable ability to
maintain blood homeostasis in hibernating squirrels.
PMID- 28501916
TI - MicroRNAs in injury and repair.
AB - Organ damage and resulting pathologies often involve multiple deregulated
pathways. MicroRNAs (miRNAs) are short, non-coding RNAs that regulate a multitude
of genes at the post-transcriptional level. Since their discovery over two
decades ago, miRNAs have been established as key players in the molecular
mechanisms of mammalian biology including the maintenance of normal homeostasis
and the regulation of disease pathogenesis. In recent years, there has been
substantial progress in innovative techniques to measure miRNAs along with
advances in targeted delivery of agents modulating their expression. This has
expanded the scope of miRNAs from being important mediators of cell signaling to
becoming viable quantitative biomarkers and therapeutic targets. Currently, miRNA
therapeutics are in clinical trials for multiple disease areas and vast numbers
of patents have been filed for miRNAs involved in various pathological states. In
this review, we summarize miRNAs involved in organ injury and repair,
specifically with regard to organs that are the most susceptible to injury: the
liver, heart and kidney. In addition, we review the current state of knowledge on
miRNA biology, miRNA biomarkers and nucleotide-based therapeutics designed to
target miRNAs to prevent organ injury and promote repair.
PMID- 28501921
TI - Cranberry (Vaccinium macrocarpon) extract treatment improves triglyceridemia,
liver cholesterol, liver steatosis, oxidative damage and corticosteronemia in
rats rendered obese by high fat diet.
AB - PURPOSE: Obese individuals have higher production of reactive oxygen species,
which leads to oxidative damage. We hypothesize that cranberry extract (CE) can
improve this dysfunction in HFD-induced obesity in rats since it has an important
antioxidant activity. Here, we evaluated the effects of CE in food intake,
adiposity, biochemical and hormonal parameters, lipogenic and adipogenic factors,
hepatic morphology and oxidative balance in a HFD model. METHODS: At postnatal
day 120 (PN120), male Wistar rats were assigned into two groups: (1) SD (n = 36)
fed with a standard diet and (2) HFD (n = 36), fed with a diet containing 44.5%
(35.2% from lard) energy from fat. At PN150, 12 animals from SD and HFD groups
were killed while the others were subdivided into four groups (n = 12/group):
animals that received 200 mg/kg cranberry extract (SD CE, HFD CE) gavage/daily/30
days or water (SD, HFD). At PN180, animals were killed. RESULTS: HFD group showed
higher body mass and visceral fat, hypercorticosteronemia, higher liver
glucocorticoid sensitivity, cholesterol and triglyceride contents and
microsteatosis. Also, HFD group had higher lipid peroxidation (plasma and
tissues) and higher protein carbonylation (liver and adipose tissue) compared to
SD group. HFD CE group showed lower body mass gain, hypotrygliceridemia,
hypocorticosteronemia, and lower hepatic cholesterol and fatty acid synthase
contents. HFD CE group displayed lower lipid peroxidation, protein carbonylation
(liver and adipose tissue) and accumulation of liver fat compared to HFD group.
CONCLUSION: Although adiposity was not completely reversed, cranberry extract
improved the metabolic profile and reduced oxidative damage and steatosis in HFD
fed rats, which suggests that it can help manage obesity-related disorders.
PMID- 28501923
TI - Application of objective clinical human reliability analysis (OCHRA) in
assessment of technical performance in laparoscopic rectal cancer surgery: common
mistakes and methodological issues.
PMID- 28501922
TI - SEPP1 polymorphisms modulate serum glucose and lipid response to Brazil nut
supplementation.
AB - PURPOSE: The consumption of Brazil nuts has been associated with benefits to
lipid metabolism and reductions in total cholesterol and LDL concentrations. They
are the richest natural source of selenium which has essential functions in human
physiology. Genetic polymorphisms in Selenoprotein P could impair lipid and
glucose metabolisms. The aim of this work was to verify the influence of
polymorphisms in genes for selenoproteins on blood lipid levels after dietary
supplementation with Brazil nuts in healthy adults. METHODS: The study included
130 healthy volunteers selected at the University of Sao Paulo, Brazil. They were
supplemented with one nut a day for 8 weeks, followed by 8 weeks without
intervention. The following analyses were performed: anthropometric measurements,
serum fasting glucose, lipid profile, C-reactive protein and plasma MDA levels.
The volunteers were genotyped for SNPs rs1050450, rs3811699, rs1800699, rs713041,
rs3877899, rs7579, rs34713741, and rs5845 in genes for selenoproteins. RESULTS:
The concentrations of total cholesterol and fasting glucose levels decreased
after 8 weeks of supplementation (p < 0.05). Glucose levels were modulated by
rs3877899 in SEPP1, with significantly lower levels observed for individuals with
the GA + AA genotype (p = 0.025). In addition, rs7579 was associated with
cholesterol concentrations, which were significantly lower for individuals with
the GG genotype (p = 0.053). CONCLUSIONS: Supplementation with one Brazil nut a
day for 8 weeks reduced total cholesterol and glucose levels. Furthermore, our
results suggest that rs3877899 might be associated with glucose concentrations
and rs7579 with cholesterol concentrations. Therefore, the effect of genetic
variations should be considered in future nutritional interventions evaluating
the response to Brazil nut supplementation.
PMID- 28501924
TI - Anterior rectal duplication treated with transanal endoscopic microsurgery.
PMID- 28501925
TI - Colonoscope-mediated vaginoscopy for diagnostic evaluation of colovaginal
fistulas.
PMID- 28501926
TI - An outbreak of Clostridium difficile PCR ribotype 027 in Spain: risk factors for
recurrence and a novel treatment strategy.
AB - An outbreak of Clostridium difficile infection (CDI) caused by ribotype 027
(B1/NAP1) began in our hospital in November 2014, and produced 141 episodes in
the following months. The aim of this study is to describe this outbreak, assess
risk factors for recurrence of CDI-027 and to analyze the implementation of a
novel treatment strategy. This is a prospective study of all patients with CDI
027, from November 2014 to November 2015. The epidemiological data were collected
daily for each patient. We compared clinical characteristics and treatment
between patients with and without recurrence of CDI-027. Interestingly, liver
cirrhosis was present in 22% of the patients, and most of them received
prophylaxis for hepatic encephalopathy with rifaximin. Patients were also taking
antimicrobial drugs (93.6%) and proton pump inhibitors (80.1%). Overall, 27
(23.5%) patients had a first recurrence of CDI-027. Liver cirrhosis increased the
risk of recurrence (44.4% vs 14.8%). Patients treated with a prolonged oral
vancomycin regimen vs the conventional regimen (oral metronidazole or 10 days of
vancomycin) had fewer recurrences (8.6 versus 44.7% [p <= 0.01]; OR, 0.91; 95%
CI, 0.028-0.294) and less attributable mortality (0% versus 7.1%; p = 0.058). We
report an outbreak of CDI-027, mainly in patients with liver cirrhosis.
Recurrence of CDI-027 was more common in those patients. A novel approach
involving high-dose prolonged vancomycin taper as a first-line treatment,
together with a bundle of outbreak measures, seemed to reduce the number of cases
of CDI-027, recurrences, and attributable mortality. Nevertheless, this approach
warrants further investigation.
PMID- 28501927
TI - Cytokine gene polymorphism associations with congenital cytomegalovirus infection
and sensorineural hearing loss.
AB - Cytomegalovirus (CMV) is the most common viral agent of congenital infections and
a leading nongenetic cause of sensorineural hearing loss (SNHL). The host
immunologic factors that render a developing foetus prone to intrauterine CMV
infection and development of hearing loss are unknown. The aim of this study was
to assess the potential associations between the polymorphisms within cytokine
and cytokine receptors genes, and the risk of congenital CMV infection, and the
hearing outcome. A panel of 11 candidate single nucleotide polymorphisms (SNPs):
TNF rs1799964, TNF rs1800629, TNFRSF1A rs4149570, IL1B rs16944, IL1B rs1143634,
IL10 rs1800896, IL10RA rs4252279, IL12B rs3212227, CCL2 rs1024611, CCL2 rs13900,
CCR5 rs333 was genotyped in 470 infants (72 with confirmed intrauterine CMV
infection and 398 uninfected controls), and related to congenital CMV infection,
and the outcome. In multivariate analysis, the IL1B rs16944 TT and TNF rs1799964
TC genotypes were significantly associated with intrauterine CMV infection (aOR =
2.32; 95% CI, 1.11-4.89; p = 0.032, and aOR = 2.17, 95% CI, 1.25-3.77; p = 0.007,
respectively). Twenty-two out of 72 congenitally infected newborns had confirmed
SNHL. Carriers of CT or TT genotype of CCL2 rs13900 had increased risk of hearing
loss at birth and at 6 months of age (aOR = 3.59; p = 0.028 and aOR = 4.10; p =
0.039, respectively). This is the first study to report an association between
SNPs in IL1B, TNF, and CCL2, and susceptibility to congenital CMV infection (IL1B
and TNF) and SNHL (CCL2).
PMID- 28501928
TI - The Behavioral and Social Sciences: Contributions and Opportunities in Academic
Medicine.
AB - The Association of American Medical Colleges plays a leading role in supporting
the expansion and evolution of academic medicine and medical science in North
America, which are undergoing high-velocity change. Behavioral and social science
concepts have great practical value when applied to the leadership practices and
administrative structures that guide and support the rapid evolution of academic
medicine and medical sciences. The authors are two behavioral and social science
professionals who serve as academic administrators in academic medical centers.
They outline their career development and describe the many ways activities have
been shaped by their work with the Association of American Medical Colleges.
Behavioral and social science professionals are encouraged to become change
agents in the ongoing transformation of academic medicine.
PMID- 28501930
TI - Association of GWAS-Reported Variant rs11196288 near HABP2 with Ischemic Stroke
in Chinese Han Population.
AB - A recent genome-wide association analysis identified a novel single nucleotide
polymorphism locus on chromosome 10q25.3 (rs11196288, near HABP2) associated with
the risk of early-onset ischemic stroke (IS) in European population, but not with
late-onset IS. However, the role of this genome-wide association study (GWAS)
reported variant in ischemic stroke in Chinese Han population remained unknown.
In our study, 389 adult ischemic stroke patients with an age of onset <60 years
and 389 matched healthy controls were enrolled to investigate association of
rs11196288 genotypes with early-onset ischemic stroke and its subtypes; the
association was further examined in another independent population consisting of
349 ischemic stroke patients with an age of onset ?60 years and 349 matched
healthy individuals. Logistic regression analysis showed no significant
association between rs11196288 and early-onset ischemic stroke (IS), large artery
atherosclerotic (LAA) stroke, or small vessel disease (SVD) stroke (all P >
0.050). Nevertheless, in subgroup analysis of the older population, rs11196288
presented significant effect on late-onset SVD stroke susceptibility in the
dominant model (GG/GA vs AA, OR 1.70; 95%CI 1.02 to 2.85; P = 0.042). The results
indicated that the role of rs11196288 polymorphism in ischemic stroke
susceptibility in Chinese Han population may be different from that in European.
Larger studies with diverse populations are warranted to confirm and extend our
findings.
PMID- 28501931
TI - Effect of allyl isothiocyanate on NF-kappaB signaling in 7,12
dimethylbenz(a)anthracene and N-methyl-N-nitrosourea-induced mammary
carcinogenesis.
AB - BACKGROUND: Inflammation plays a pivotal role in the process of carcinogenesis
and phytochemicals have anti-inflammatory properties gaining more importance in
cancer chemoprevention. The present study aimed to investigate the anti
inflammatory effect of allyl isothiocyanate (AITC) on 7,12
dimethylbenz(a)anthracene (DMBA)- and N-methyl-N-nitrosourea (MNU)-induced
mammary carcinogenesis in female Sprague-Dawley rats. METHODS: RT-PCR and western
blot analysis showed that inflammatory markers such as NF-kappaB p65, TNF-alpha,
and IL-6 were overexpressed in mammary tumor tissues. Histological analysis of
tumor tissues shows abnormality in hematoxylin and eosin (H&E) staining and
toluidine blue (TB) staining of mast cell content, and lipid accumulation in oil
red O staining. RESULTS: Administration of AITC (20 mg/kg bw) to carcinogen
injected rats significantly decreased the expression of NF-kappaB p65, TNF-alpha,
and IL-6 in mammary tissues. Further, molecular docking study demonstrates the
binding of AITC to NF-kappaB p65. Remarkably, AITC treatments control the growth
of cancer cells as clearly evidenced by histopathological analysis. Staining of
mammary tissues for mast cells and lipids indicates that AITC treatment to
carcinogen-administrated rats significantly reduced mammary tumorigenesis.
CONCLUSIONS: The result suggests that AITC has anti-inflammatory potential to
prevent DMBA- and MNU-induced mammary carcinogenesis in rats.
PMID- 28501932
TI - Factors affecting serum sclerostin in postmenopausal women.
PMID- 28501929
TI - Hyponatremia associated with human herpesvirus-6 (HHV-6) encephalitis after
allogeneic hematopoietic stem cell transplantation: A presentation different from
HHV-6 myelitis.
AB - Human herpesvirus-6 (HHV-6) encephalitis and myelitis following allogeneic
hematopoietic stem cell transplantation (HSCT) is frequently life-threatening. We
retrospectively evaluated the clinical significance of hyponatremia in cases of
HHV-6 encephalitis/myelitis. Using an institutional database and medical records,
we identified and retrospectively analyzed 16 cases of HHV-6 encephalitis and/or
myelitis after allogeneic HSCT. HHV-6 encephalitis and myelitis were defined as
the symptoms/signs with HHV-6-DNA in the cerebrospinal fluid. Seizure and memory
disorder were defined as symptoms/signs of encephalitis, and dysesthesia and
vesicorectal disorder as those of myelitis. Five patients developed encephalitis
with or without myelitis, and 11 patients developed myelitis alone. Hyponatremia
(median 129.1 mEq/L; range 125.9-130.1) was observed in all five patients with
HHV-6 encephalitis at diagnosis, and values were significantly lower than those
in patients with HHV-6 myelitis alone (median 137.6; range 134.0-142.2; P <
0.01). In three of the five patients with encephalitis, the decrease in sodium
level preceded the clinical onset of encephalitis by one or two days. These
results suggest that hyponatremia may be an important manifestation of HHV-6
encephalitis, but not of myelitis, and could be a useful tool for the early
prediction or diagnosis of HHV-6 encephalitis.
PMID- 28501933
TI - The influence of MCAT and GPA preadmission academic metrics on interview scores.
AB - Medical school admissions interviews are used to assess applicants' nonacademic
characteristics as advocated by the Association of American Medical Colleges'
Advancing Holistic Review Initiative. The objective of this study is to determine
whether academic metrics continue to significantly influence interviewers' scores
in holistic processes by blinding interviewers to applicants' undergraduate grade
point averages (uGPA) and Medical College Admission Test (MCAT). This study
examines academic and demographic predictors of interview scores for two
applicant cohorts at the University of Michigan Medical School. In 2012,
interviewers were provided applicants' uGPA and MCAT scores; in 2013, these
academic metrics were withheld from interviewers' files. Hierarchical regression
analysis was conducted to examine the influence of academic and demographic
variables on overall cohort interview scores. When interviewers were provided
uGPA and MCAT scores, academic metrics explained more variation in interview
scores (7.9%) than when interviewers were blinded to these metrics (4.1%).
Further analysis showed a statistically significant interaction between cohort
and uGPA, indicating that the association between uGPA and interview scores was
significantly stronger for the 2012 unblinded cohort compared to the 2013 blinded
cohort (beta = .573, P < .05). By contrast, MCAT scores had no interactive
effects on interviewer scores. While MCAT scores accounted for some variation in
interview scores for both cohorts, only access to uGPA significantly influenced
interviewers' scores when looking at interaction effects. Withholding academic
metrics from interviewers' files may promote assessment of nonacademic
characteristics independently from academic metrics.
PMID- 28501934
TI - CX-4945: the protein kinase CK2 inhibitor and anti-cancer drug shows anti-fungal
activity.
AB - CX-4945 is a selective inhibitor of protein kinase CK2 exhibiting clinical
significance. Its antitumor properties arise from the abrogation of CK2-mediated
pro-survival cellular pathways. The presented data reveal the influence of CX
4945 on the growth of yeast cells showing variable potency against Saccharomyces
cerevisiae deletion strains with different contents of CK2 subunits. The
catalytic subunit CK2alpha appears to sensitize yeast to the CX-4945 action.
Moreover, the compound suppresses hyphal growth and cell adhesion of Candida
albicans, thereby abolishing some hallmarks of invasiveness of the pathogen. It
is known that cancer patients are more prone to fungal infections. Our data
unveil the dual-activity of CX-4945; when used in anti-cancer therapy, it may
simultaneously prevent cancer-associated candidiasis.
PMID- 28501935
TI - Early gastric adenocarcinoma arising within foveolar-type dysplasia in a patient
with Muir-Torre variant Lynch syndrome.
PMID- 28501936
TI - Maternal Sensitivity Predicts Fewer Sleep Problems at Early Adolescence for
Toddlers with Negative Emotionality: A Case of Differential Susceptibility.
AB - Theory underscores the importance of parenting in sleep development, but few
studies have examined whether links vary by temperament. To address this gap, we
tested whether potential links between early maternal sensitivity and early
adolescent sleep problems varied by child negative emotionality and delay of
gratification. Using data from the National Institute of Child Health and Human
Development Study of Early Child Care and Youth Development (N = 820), we found
that high maternal sensitivity predicted fewer bedtime problems and longer sleep
duration at 6th grade for toddlers with high negative emotionality, whereas low
maternal sensitivity predicted the reverse. No differences were observed for low
negative emotionality. Moreover, delay of gratification predicted fewer bedtime
problems at 6th grade, but did not moderate associations between maternal
sensitivity, negative emotionality, and sleep. Findings demonstrate that high,
but not low, negative emotionality renders toddlers differentially susceptible
and receptive to maternal sensitivity in relation to sleep.
PMID- 28501937
TI - Expression of PD-L1 in keratoacanthoma and different stages of progression in
cutaneous squamous cell carcinoma.
AB - BACKGROUND: Programmed cell death 1 (PD-1) and its ligands (PD-L1) play a major
role in the immune responses of a variety of cancers. OBJECTIVES: To investigate
the expression of PD-L1 in different progression forms of cutaneous squamous cell
carcinoma (cSCC) and keratoacanthoma (KA). METHODS: We performed
immunohistochemical staining of 21 KA, 26 actinic keratoses (AK), 20 Bowen's
diseases (BD), and 26 high-risk cSCC. The staining patterns were assessed using
the tumour proportion score and staining intensity evaluation. Immunohistology
scores were statistically analysed. RESULTS: PD-L1 expression of tumour cells as
well as tumour-infiltrating cells (TILs) was significantly higher in KA and cSCC
when compared to AK and BD (P = 0.00028 and P = 0.00033, respectively). We
observed a very strong positive correlation between the PD-L1 protein expression
of tumour cells of KA and the PD-L1 protein expression of TILs (r = 0.97; P <
0.0001). A similar correlation was also found for cSCC (r = 0.86; P < 0.0001).
The percentage of PD-L1 + tumours was 33.3% for KA and 26.9% for cSCC. Similarly,
the percentage of PD-L1 + TILs in KA and cSCC was 33.3 and 34.6%, respectively.
CONCLUSIONS: PD-L1 is differently expressed in cSCC and closely related non
melanoma skin cancer. cSCC exhibit PD-L1 expression in a fourth of cases,
indicating that PD1/PD-L1 inhibitors might be beneficial in a proportion of
patients with an inoperable or metastatic cSCC. Unlike AK and BD, TILs and tumour
cells of KA and cSCC present very similar PD-L1 expression profiles indicating a
common immune escape mechanism.
PMID- 28501938
TI - Zoledronic acid renders human M1 and M2 macrophages susceptible to Vdelta2+
gammadelta T cell cytotoxicity in a perforin-dependent manner.
AB - Vdelta2+ T cells are a subpopulation of gammadelta T cells in humans that are
cytotoxic towards cells which accumulate isopentenyl pyrophosphate. The nitrogen
containing bisphosphonate, zoledronic acid (ZA), can induce tumour cell lines to
accumulate isopentenyl pyrophosphate, thus rendering them more susceptible to
Vdelta2+ T cell cytotoxicity. However, little is known about whether ZA renders
other, non-malignant cell types susceptible. In this study we focussed on
macrophages (Mphis), as these cells have been shown to take up ZA. We
differentiated peripheral blood monocytes from healthy donors into Mphis and then
treated them with IFN-gamma or IL-4 to generate M1 and M2 Mphis, respectively. We
characterised these Mphis based on their phenotype and cytokine production and
then tested whether ZA rendered them susceptible to Vdelta2+ T cell cytotoxicity.
Consistent with the literature, IFN-gamma-treated Mphis expressed higher levels
of the M1 markers CD64 and IL-12p70, whereas IL-4-treated Mphis expressed higher
levels of the M2 markers CD206 and chemokine (C-C motif) ligand 18. When treated
with ZA, both M1 and M2 Mphis became susceptible to Vdelta2+ T cell cytotoxicity.
Vdelta2+ T cells expressed perforin and degranulated in response to ZA-treated
Mphis as shown by mobilisation of CD107a and CD107b to the cell surface.
Furthermore, cytotoxicity towards ZA-treated Mphis was sensitive-at least in part
to the perforin inhibitor concanamycin A. These findings suggest that ZA can
render M1 and M2 Mphis susceptible to Vdelta2+ T cell cytotoxicity in a perforin
dependent manner, which has important implications regarding the use of ZA in
cancer immunotherapy.
PMID- 28501939
TI - Dianthin-30 or gelonin versus monomethyl auristatin E, each configured with an
anti-calcitonin receptor antibody, are differentially potent in vitro in high
grade glioma cell lines derived from glioblastoma.
AB - We have reported that calcitonin receptor (CTR) is widely expressed in biopsies
from the lethal brain tumour glioblastoma by malignant glioma and brain tumour
initiating cells (glioma stem cells) using anti-human CTR antibodies. A
monoclonal antibody against an epitope within the extracellular domain of CTR was
raised (mAb2C4) and chemically conjugated to either plant ribosome-inactivating
proteins (RIPs) dianthin-30 or gelonin, or the drug monomethyl auristatin E
(MMAE), and purified. In the high-grade glioma cell line (HGG, representing
glioma stem cells) SB2b, in the presence of the triterpene glycoside SO1861, the
EC50 for mAb2C4:dianthin was 10.0 pM and for mAb2C4:MMAE [antibody drug conjugate
(ADC)] 2.5 nM, 250-fold less potent. With the cell line U87MG, in the presence of
SO1861, the EC50 for mAb2C4:dianthin was 20 pM, mAb2C4:gelonin, 20 pM, compared
to the ADC (6.3 nM), which is >300 less potent. Several other HGG cell lines that
express CTR were tested and the efficacies of mAb2C4:RIP (dianthin or gelonin)
were similar. Co-administration of the enhancer SO1861 purified from plants
enhances lysosomal escape. Enhancement with SO1861 increased potency of the
immunotoxin (>3 log values) compared to the ADC (1 log). The uptake of antibody
was demonstrated with the fluorescent conjugate mAb2C4:Alexa Fluor 568, and the
release of dianthin-30:Alexa Fluor488 into the cytosol following addition of
SO1861 supports our model. These data demonstrate that the immunotoxins are
highly potent and that CTR is an effective target expressed by a large proportion
of HGG cell lines representative of glioma stem cells and isolated from
individual patients.
PMID- 28501940
TI - Common extracellular matrix regulation of myeloid cell activity in the bone
marrow and tumor microenvironments.
AB - The complex interaction between cells undergoing transformation and the various
stromal and immunological cell components of the tumor microenvironment (TME)
crucially influences cancer progression and diversification, as well as endowing
clinical and prognostic significance. The immunosuppression characterizing the
TME depends on the recruitment and activation of different cell types including
regulatory T cells, myeloid-derived suppressor cells, and tumor-associated
macrophages. Less considered is the non-cellular component of the TME. Here, we
focus on the extracellular matrix (ECM) regulatory activities that, within the
TME, actively contribute to many aspects of tumor progression, acting on both
tumor and immune cells. Particularly, ECM-mediated regulation of tumor-associated
immunosuppression occurs through the modulation of myeloid cell expansion,
localization, and functional activities. Such regulation is not limited to the
TME but occurs also within the bone marrow, wherein matricellular proteins
contribute to the maintenance of specialized hematopoietic stem cell niches
thereby regulating their homeostasis as well as the generation and expansion of
myeloid cells under both physiological and pathological conditions. Highlighting
the commonalities among ECM-myeloid cell interactions in bone marrow and TME, in
this review we present a picture in which myeloid cells might sense and respond
to ECM modifications, providing different ECM-myeloid cell interfaces that may be
useful to define prognostic groups and to tailor therapeutic interventions.
PMID- 28501941
TI - Paracrine release of IL-2 and anti-CTLA-4 enhances the ability of artificial
polymer antigen-presenting cells to expand antigen-specific T cells and inhibit
tumor growth in a mouse model.
AB - Accumulating evidence indicates that bead-based artificial antigen-presenting
cells (aAPCs) are a powerful tool to induce antigen-specific T cell responses in
vitro and in vivo. To date, most conventional aAPCs have been generated by
coupling an antigen signal (signal 1) and one or two costimulatory signals, such
as anti-CD28 with anti-LFA1 or anti-4-1BB (signal 2), onto the surfaces of cell
sized or nanoscale magnetic beads or polyester latex beads. The development of a
biodegradable scaffold and the combined use of multiple costimulatory signals as
well as third signals for putative clinical applications is the next step in the
development of this technology. Here, a novel biodegradable aAPC platform for
active immunotherapy was developed by co-encapsulating IL-2 and anti-CTLA-4
inside cell-sized polylactic-co-glycolic acid microparticles (PLGA-MPs) while co
coupling an H-2Kb/TRP2-Ig dimer and anti-CD28 onto the surface. Cytokines
(activating signal) and antibodies (anti-inhibition signal) were efficiently co
encapsulated in PLGA-MP-based aAPCs and co-released without interfering with each
other. The targeted, sustained co-release of IL-2 and anti-CTLA-4 achieved
markedly enhanced, synergistic effects in activating and expanding tumor antigen
specific T cells both in vitro and in vivo, as well as in inhibiting tumor growth
in a mouse melanoma model, as compared with conventional two-signal aAPCs and IL
2 or anti-CTLA-4 single-released aAPCs. These data revealed the feasibility and
importance of the paracrine release of multiple costimulatory molecules and
cytokines from biodegradable aAPCs and thus provide a proof of principle for the
future use of polymeric aAPCs for active immunotherapy of tumors and infectious
diseases.
PMID- 28501942
TI - Pulmonary nodule classification with deep residual networks.
AB - : PURPOSE : Lung cancer has the highest death rate among all cancers in the USA.
In this work we focus on improving the ability of computer-aided diagnosis (CAD)
systems to predict the malignancy of nodules from cropped CT images of lung
nodules. METHODS: We evaluate the effectiveness of very deep convolutional neural
networks at the task of expert-level lung nodule malignancy classification. Using
the state-of-the-art ResNet architecture as our basis, we explore the effect of
curriculum learning, transfer learning, and varying network depth on the accuracy
of malignancy classification. RESULTS: Due to a lack of public datasets with
standardized problem definitions and train/test splits, studies in this area tend
to not compare directly against other existing work. This makes it hard to know
the relative improvement in the new solution. In contrast, we directly compare
our system against two state-of-the-art deep learning systems for nodule
classification on the LIDC/IDRI dataset using the same experimental setup and
data set. The results show that our system achieves the highest performance in
terms of all metrics measured including sensitivity, specificity, precision,
AUROC, and accuracy. CONCLUSIONS: The proposed method of combining deep residual
learning, curriculum learning, and transfer learning translates to high nodule
classification accuracy. This reveals a promising new direction for effective
pulmonary nodule CAD systems that mirrors the success of recent deep learning
advances in other image-based application domains.
PMID- 28501944
TI - Sociodemographic predictors of participation in colorectal cancer screening.
AB - PURPOSE: Colorectal cancer screening by inviting citizens to complete a test for
blood in faeces was initiated in Denmark in 2014. We have examined
sociodemographic predictors that influence participation to identify factors that
could be targeted to increase compliance. METHODS: National registers were used
to link data on invitations for colorectal cancer screening in Denmark from 2014
to 2015. Region of residence, age, gender, immigration status, income,
educational level and marital status were identified. Logistic regression
analysis was used to estimate the risk of non-participation for invited citizens
while adjusting for all other sociodemographic variables. RESULTS: A total of
854,237 individuals were included in the analysis. The national participation
proportion was 65.33%, with significant differences between sociodemographic
groups. Participation proportions were the lowest in non-Western immigrants
(53.00%), individuals without a partner (54.05%) and those in the lowest income
quartile (54.65%), with subgroup participation as low as 40.56%. The highest
participation proportion was seen in individuals in the highest income quartile
(71.56%). Region of residence, age, gender, educational level, income quartile,
marital status and immigration status all had statistically significant
independent differences in risk of non-participation after full model adjustment.
CONCLUSION: Participation in colorectal cancer screening was high in Denmark in
2014 and 2015. Large differences in participation were seen between
sociodemographic subgroups, potentially resulting in social inequality in the
benefits from screening. Future efforts to increase participation should focus on
the low compliance subgroups, such as singles, non-Western immigrants and people
from the lowest socioeconomic groups.
PMID- 28501943
TI - Protocol for the development of a Core Outcome Set (COS) for hemorrhoidal
disease: an international Delphi study.
AB - PURPOSE: Over the last decade, many studies were performed regarding treatment
options for hemorrhoidal disease. Randomised controlled trials (RCTs) should have
well-defined primary and secondary outcomes. However, the reported outcome
measures are numerous and diverse. The heterogeneity of outcome definition in
clinical trials limits transparency and paves the way for bias. The development
of a core outcome set (COS) helps minimizing this problem. A COS is an agreed
minimum set of outcomes that should be measured and reported in all clinical
trials of a specific disease. The aim of this project is to generate a COS
regarding the outcome of treatment after hemorrhoidal disease. METHODS: A Delphi
study will be performed by an international steering group healthcare
professionals and patients with the intention to create a standard outcome set
for future clinical trials for the treatment of hemorrhoidal disease. First, a
literature review will be conducted to establish which outcomes are used in
clinical trials for hemorrhoidal disease. Secondly, both healthcare professionals
and patients will participate in several consecutive rounds of online
questionnaires and a face-to-face meeting to refine the content of the COS.
DISCUSSION: Development of a COS for hemorrhoidal disease defines a minimum
outcome-reporting standard and will improve the quality of research in the
future.
PMID- 28501945
TI - Macrophage polarization differs between apical granulomas, radicular cysts, and
dentigerous cysts.
AB - OBJECTIVES: Apical periodontitis can appear clinically as apical granulomas or
radicular cysts. There is evidence that immunologic factors are involved in the
pathogenesis of both pathologies. In contrast to radicular cysts, the dentigerous
cysts have a developmental origin. Macrophage polarization (M1 vs M2) is a main
regulator of tissue homeostasis and differentiation. There are no studies
comparing macrophage polarization in apical granulomas, radicular cysts, and
dentigerous cysts. MATERIALS AND METHODS: Forty-one apical granulomas, 23
radicular cysts, and 23 dentigerous cysts were analyzed in this study. A tissue
microarray (TMA) of the 87 consecutive specimens was created, and CD68-, CD11c-,
CD163-, and MRC1-positive macrophages were detected by immunohistochemical
methods. TMAs were digitized, and the expression of macrophage markers was
quantitatively assessed. RESULTS: Radicular cysts are characterized by M1
polarization of macrophages while apical granulomas show a significantly higher
degree of M2 polarization. Dentigerous cysts have a significantly lower M1
polarization than both analyzed periapical lesions (apical granulomas and
radicular cysts) and accordingly, a significantly higher M2 polarization than
radicular cysts. Macrophage cell density in dentigerous cysts is significantly
lower than in the periapical lesions. CONCLUSIONS: The development of apical
periodontitis towards apical granulomas or radicular cysts might be directed by
macrophage polarization. Radicular cyst formation is associated with an increased
M1 polarization of infiltrating macrophages. In contrast to radicular cysts,
dentigerous cysts are characterized by a low macrophage infiltration and a high
degree of M2 polarization, possibly reflecting their developmental rather than
inflammatory origin. CLINICAL RELEVANCE: As M1 polarization of macrophages is
triggered by bacterial antigens, these results underline the need for sufficient
bacterial clearance during endodontic treatment to prevent a possible M1
macrophage-derived stimulus for radicular cyst formation.
PMID- 28501946
TI - Application of International Caries Detection and Assessment System (ICDAS) and
Caries Management by Risk Assessment (CAMBRA) systems in child cancer patients: a
clinical case report.
AB - BACKGROUND: Leukaemia represents 30-40% of all paediatric malignant tumours and
is the main cause of death in patients aged <15 years. One of the main
complications in these patients is infection, which may often occur in the oral
cavity. Chemotherapy-related oral health problems may be reduced by oral
healthcare strategies based on the International Caries Detection and Assessment
System (ICDAS) and Caries Management by Risk Assessment (CABRA). CASE REPORT: A
case is reported of a 14-year-old girl treated for leukaemia who presented with
established dental caries lesions which were classified and treated according to
ICDAS and CABRA protocols. After three, no new caries was observed. FOLLOW-UP AND
CONCLUSION: ICDAS and CAMBRA provide useful and effective guidance for the
avoidance of dental and systemic problems. Their introduction into standard
practice could reduce the legal difficulties derived from dental treatment in
these patients.
PMID- 28501947
TI - Current status of superficial pharyngeal squamous cell carcinoma in Japan.
AB - BACKGROUND: To investigate the status and treatment of superficial pharyngeal
squamous cell carcinoma in Japan. METHODS: We analyzed all cases diagnosed
between 2011 and 2013, as recorded in the national database of hospital-based
cancer registries. We extracted data on patient sex, age, tumor locations,
histology, presentation routes, initial treatments, and TNM stages. Additionally,
we compared the characteristics of pharyngeal carcinoma to those of esophageal
cancer. RESULTS: A total of 16,521 oropharyngeal and hypopharyngeal cancers from
409 institutions were included. Diagnosis of Tis tumors was infrequent, and both
cancers were likely to be diagnosed at an advanced stage (n = 866, 5.3%). Tis
diseases were the most commonly detected during follow-up examinations for other
diseases (n = 608, 70%). While more oropharyngeal Tis patients were men compared
to T1-4 patients (88 vs 82%, respectively), hypopharyngeal cancer patients
comprised an equally high proportion of men (94 vs 92%, respectively). The most
common location of oropharyngeal Tis tumors was the posterior wall (32%), whereas
T1-4 tumors were most commonly found on the lateral wall (36%). In hypopharyngeal
cancer, both Tis and T1-4 were most commonly located in the pyriform sinus (62%).
The proportion of Tis tumors diagnosed at individual institutions showed a
positive correlation with the number of endoscopic treatments (r = 0.32, P <
0.001) and the number of esophageal cancer cases (r = 0.37, P < 0.001).
CONCLUSION: Our national database study elucidated the current characteristics of
superficial pharyngeal squamous cell carcinoma patients in Japan. Further
improvements in early diagnosis and standardized treatments are warranted.
PMID- 28501948
TI - Corneal tomography and biomechanics in primary pterygium.
AB - PURPOSE: To study the Scheimpflug's imaging and corneal biomechanics in primary
pterygium. METHODS: A prospective observational study of 55 patients with
unilateral primary nasal pterygium was done. The normal fellow eyes of patients
with pterygium were taken as controls. Clinical parameters noted included visual
acuity, values of corneal curvature by doing Scheimpflug imaging, wavefront
aberrations in terms of higher and lower-order aberrations and corneal hysteresis
(CH) as well as corneal resistance factor (CRF) values by using ocular response
analyzer. RESULTS: Of the total 55 patients, mean age was 43.0 + 11.4 years
(range: 20-72 years). Mean LogMar uncorrected visual acuity in pterygium eyes and
control eyes was 0.21 + 0.20 and 0.12 + 0.15, respectively (p = 0.016). On
Scheimpflug imaging the mean anterior corneal curvature values (Ka1/Ka2 D) were
41.09 + 3.38/44.33 + 2.29 in pterygium eyes, 43.13 + 1.79/43.98 + 2.17 in control
eyes (p < 0.0005) and mean posterior corneal curvature (Kp1/Kp2 D) values were
6.14 + 0.39/6.53 + 0.43 in pterygium eyes and 6.13 + 0.28/6.46 + 0.47 in control
eyes (p > 0.05). Analysis of corneal aberrations showed significantly higher
corneal wavefront aberrations in pterygium eyes. Highest correlation of corneal
astigmatism was noted with corneal area encroached by pterygium (rho = 0.540 for
LOA and 0.553 for HOA) and distance from pupillary center (rho = 0.531 for LOA
and 0.564 for HOA). Corneal biomechanical parameters including CH and CRF were
found to be lower in the pterygium eyes, though not statistically significant (p
value 0.60 and 0.59, respectively). CONCLUSION: Pterygium leads to deterioration
of visual performance not only by causing refractive and topographic changes but
also by causing a significant increase in corneal wavefront aberrations.
PMID- 28501950
TI - Focus on severe infections.
PMID- 28501951
TI - Video laryngoscopy for ICU intubation: should it be standard of care?
PMID- 28501949
TI - Relationship between intracranial internal carotid artery calcification and
enlarged cerebral perivascular space.
AB - PURPOSE: The association between intracranial internal carotid artery (IICA)
calcification and lacunes, white matter hyperintensity (WMH), and cerebral
microbleeds (CMBs) has been well researched. However, enlarged cerebral
perivascular space (PVS) has not yet been reported to correlate with intracranial
internal carotid artery calcification. Therefore, the primary aim of this study
was to investigate the relationship between IICA calcification and enlarged PVS.
METHODS: A total of 189 patients with ischemic stroke in the middle cerebral
artery territory who presented within 7 days of ictus from 2012 to 2015 were
enrolled respectively. All patients were required to have undergone head computed
tomography, magnetic resonance imaging, susceptibility-weighted magnetic
resonance imaging, magnetic resonance angiography, or computed tomography
angiography. Clinical characteristics were recorded. IICA calcification and
enlarged PVS were semi-quantitatively evaluated, and the presence of lacunes,
WMH, and CMBs was recorded. RESULTS: Of the 189 patients, 63.5% were male. Mean
age of the patients was 68.6 +/- 12.2 years. There were 104 patients with IICA
calcification. Age, diabetes mellitus, lacunes, and white matter hyperintensity
were significantly associated with IICA calcification (P < 0.05). Multivariate
logistic regression analysis showed that age, diabetes mellitus, and lacunes were
independent predictors of IICA calcification (P < 0.05). A lower risk of IICA
calcification was found in patients with a higher enlarged PVS score (P = 0.004).
CONCLUSION: Higher enlarged PVS scores were associated with a lesser degree of
IICA calcification. There appears to be a relationship between reduced risk of
IICA calcification and enlarged PVS.
PMID- 28501952
TI - Final adult height in long-term growth hormone-treated achondroplasia patients.
AB - : The objective of this study was to evaluate the gain in final height of
achondroplasia (ACH) patients with long-term growth hormone (GH) treatment. We
analyzed medical data of 22 adult patients (8 males and 14 females) treated with
GH at a dose of 0.05 mg/kg/day. Optionally, tibial lengthening (TL) was performed
with the Ilizalov method in 15 patients and TL as well as femoral lengthening
(FL) in 6 patients. Concomitant gonadal suppression therapy with buserelin
acetate was applied in 13 patients. The mean treatment periods with GH were 10.7
+/- 4.0 and 9.3 +/- 2.5 years for males and females, respectively. GH treatment
augmented the final height +0.60 +/- 0.52 SD (+3.5 cm) and +0.51 +/- 1.29 SD
(+2.8 cm) in males and females compared to non-treated ACH patients,
respectively. Final height of ACH patients that underwent GH and TL increased
+1.72 +/- 0.72 SD (+10.0 cm) and +1.95 +/- 1.34 SD (+9.8 cm) in males and
females, respectively. GH, TL, and FL increased their final height +2.97 SD
(+17.2 cm) and +3.41 +/- 1.63 SD (+17.3 cm) in males and females, respectively.
Gonadal suppression therapy had no impact on final height. CONCLUSIONS: Long-term
GH treatment contributes to 2.6 and 2.1% of final adult height in male and female
ACH patients, respectively.
PMID- 28501953
TI - Evaluating the contributions of muscle activity and joint kinematics to weight
perception across multiple joints.
AB - Perceived heaviness is clearly a function of muscle activity: objects feel heavy,
in part because they are lifted with more force than lighter feeling objects.
Recent research showed that participants scale their perceptions to the ratio of
muscle activity to lift acceleration during elbow lifts (Waddell et al. J Exp
Psychol Hum Percept Perform 42:363-374, 2016). The current study sought
psychophysiological functions relating perceived heaviness to EMG and peak lift
acceleration across multiple lifts employing different muscles as prime movers.
Participants lifted objects with three arm lifts-shoulder, elbow, and wrist-and
reported perceived heaviness. In each lift, EMG was recorded from the anterior
deltoid, biceps brachii, and forearm flexors, and peak angular acceleration was
recorded about each joint. The resulting psychophysiological functions revealed
the hypothesized ratio of muscle activity to peak lift acceleration in all lifts.
Principal component regressions showed that the EMG of the forearm flexors and
peak acceleration of the lifting joint were most relevant for perceived
heaviness. The special role of forearm flexors in perceiving heaviness across
different lifts was interpreted in terms of the invariant structure of the
inertia tensor about the wrist.
PMID- 28501954
TI - Complete genome sequence of longan witches' broom-associated virus, a novel
member of the family Potyviridae.
AB - The complete genome sequence of a new virus isolated from a longan (Dimocarpus
longan Lour.) plant showing witches' broom syndrome was determined. The viral
genome is composed of a monopartite single-stranded RNA of 9,428 nucleotides
excluding the 3' poly(A) tail and contains one large single open reading frame
encoding a polyprotein of 3086 amino acids. BLAST searches of protein databases
showed that the encoded polyprotein has a maximum amino acid sequence identity of
35% (with 85% coverage) to that of the isolate Minnesota of rose yellow mosaic
virus (RoYMV; family Potyviridae; genus not assigned). Molecular and phylogenetic
analysis of the genome and encoded protein sequences showed that the identified
virus has the general features that are characteristic of members of the family
Potyviridae although it has extremely low sequence similarity to known members of
the family Potyviridae. The name longan witches' broom-associated virus (LWBaV)
is proposed for this new virus, which may be considered a member of a new genus
in the family Potyviridae.
PMID- 28501955
TI - A case of arteriovenous fistula of the cauda equina fed by the proximal radicular
artery: anatomical features and treatment precautions.
AB - PURPOSE: Arteriovenous fistula (AVF) of the cauda equina (CE) fed by the proximal
radicular artery (PRA) is very rare, and the differentiation from that of the
filum terminale (FT) is important to avoid treatment-related injury to the CE
when endovascular treatment is selected. The authors describe a case of AVF of
the CE fed by the PRA, demonstrate the anatomical features and discuss the
treatment precautions. METHODS: A 69-year-old man presented with a transient
weakness of lower limbs. Spinal angiography and magnetic resonance (MR) imaging
revealed AVF, of which the feeding artery arose from the anterior spinal artery
(ASA), forming the fistula at L2 level to be drained into the longitudinal venous
trunk. Under a tentative diagnosis of AVF of the FT, endovascular treatment was
attempted but failed due to impossible catheterization into the ASA. Therefore,
surgery was performed. RESULTS: Intraoperative finding revealed that the feeding
artery and draining vein were not on the FT but on the CE, resulting in the
proper diagnosis of AVF of the CE. Surgical clips were applied to the draining
vein closest to the fistula, and postoperatively the symptom improved gradually.
Although we thoroughly reevaluated spinal angiography and MR images
postoperatively, AVF of the CE fed by the PRA and that of the FT were not
distinguishable. CONCLUSIONS: The authors described a case of AVF of the CE fed
by the PRA and demonstrated the difficulty of the differentiation from that of
the FT. The utmost precautions are necessary when endovascular treatment is
selected.
PMID- 28501956
TI - An in vitro evaluation of sagittal alignment in the cervical spine after
insertion of supraphysiologic lordotic implants.
AB - PURPOSE: Cervical spine malalignment can develop as a consequence of degenerative
disc disease or following spinal surgery. When normal sagittal alignment of the
spine is disrupted, further degeneration may occur adjacent to the deformity. The
purpose of this study was to investigate changes in lordosis and sagittal
alignment in the cervical spine after insertion of supraphysiologic lordotic
implants. METHODS: Eight cadaveric cervical spines (Occiput-T1) were tested. The
occiput was free to translate horizontally and vertically but constrained from
angular rotation. The T1 vertebra was rigidly fixed with a T1 tilt of 23 degrees
. Implants with varying degrees of lordosis were inserted starting with single
level constructs (C5-C6), followed by two (C5-C7), and three-level (C4-C7)
constructs. Changes in sagittal alignment, Occ-C2 angle, cervical lordosis (C2
7), and segmental lordosis were measured. RESULTS: Increasing cage lordosis led
to global increases in cervical lordosis. As implanted segmental lordosis
increased, the axial levels compensated by decreasing in lordosis to maintain
horizontal gaze. An increase in cage lordosis also corresponded with larger
changes in SVA. CONCLUSION: Reciprocal compensation was observed in the axial and
sub-axial cervical spine, with the Occ-C2 segment undergoing the largest
compensation. Adding more implant lordosis led to larger reciprocal changes and
changes in SVA. Implants with supraphysiologic lordosis may allow for additional
capabilities in correcting cervical sagittal plane deformity, following further
clinical evaluation.
PMID- 28501957
TI - Molecular analysis reveals hidden diversity in Zungaro (Siluriformes:
Pimelodidade): a genus of giant South American catfish.
AB - The genus Zungaro contains some of the largest catfish in South America. Two
valid species are currently recognized: Zungaro jahu, inhabiting the Parana and
Paraguay basins, and Zungaro zungaro, occurring in the Amazonas and Orinoco
basins. Analysing Zungaro specimens from the Amazonas, Orinoco, Paraguay and
Parana basins, based on the sequencing of COI and D-loop, we found at least three
MOTUs, indicating the existence of hidden diversity within this fish group.
Considering the ecological and economic values of this fish, our results are
surely welcomed for its conservation, disclosing new findings on its diversity
and pointing out the necessity for a detailed taxonomic revision.
PMID- 28501958
TI - Heightened perception of breast cancer risk in young women at risk of familial
breast cancer.
AB - The objective of this study was to explore the factors that influence perceived
personal risk of developing breast cancer (BC) in younger women (<35) who are
considering or have undergone bilateral prophylactic mastectomy (BPM).
Qualitative interviews guided by interpretative phenomenological analysis were
conducted with 46 women who had a strong family history of BC and had either
undergone (n = 26) or were considering (n = 20) BPM. Participants were recruited
from Australia and New Zealand via hospitals, a genetics clinic, a research
cohort, a registry and online. Three main themes were identified: information
that increases fear of BC and death, underlying anxiety and fear and screening
anxiety. A further two themes: relief following surgery and confusion about
residual risk following surgery were identified. Younger women (<35) appeared to
have heightened and sometimes inaccurate perceptions of their BC risk. They
appeared less relieved of anxiety and fear of developing BC by BPM surgery, in
comparison to previous research with older women (>40). Those who had undergone
BPM seemed more anxious about their risk of developing BC than those who were
still considering surgery. This research has important implications for practice,
particularly improving communication of accurate risk statistics. Future research
should examine why some women interpret information differently and explore the
benefits of psychological consultation for very anxious women.
PMID- 28501959
TI - Contralateral sinus involvement of surgically treated unilateral allergic fungal
rhinosinusitis.
AB - Recurrence of allergic fungal rhinosinusitis (AFRS) is well recognized. However,
there is scarcity in the literature describing involvement of the non-diseased
sinuses. We aimed to evaluate the recurrence forms of unilateral AFRS as well as
to study the possible predictor factors of developing the disease in the
contralateral side. Patients with exclusive unilateral AFRS from (2010 to 2015)
were enrolled in multi-institutional case-control study. All patients were
evaluated after endoscopic sinus surgery for recurrence. Patient's records were
reviewed for demographics, medical treatment, and clinical, radiological, and
surgical data. A total of 68 patients were identified. Delayed contralateral
involvement after the initial surgery was found in 30.8% with mean duration of
recurrence 16.9 months. A significant association was found with the presence of
pre-operative contralateral symptoms and signs of inflammation (OR 3.49, 95% CI
1.19-10.22, p value 0.02). Post-operative use of budesonide irrigation was
associated with less contralateral involvement (OR 0.11, 95% CI 0.01-0.87, p
value 0.01). Association of other variables like: comorbidities, perioperative
use of systemic steroid, radiological signs, extent of surgery, additional
surgery to the contralateral side, and post-operative use of systemic steroids
did not show statistical significance. Involvement of the contralateral sinuses
in 30% of unilateral AFRS cases is considered significant. The non-diseased
sinuses should be involved in the routine endoscopic examination and post
operative treatment. Further studies are necessary to investigate the possibility
of prophylactic surgical intervention of the non-diseased sinuses.
PMID- 28501960
TI - A modified minimally invasive technique for intra-articular displaced calcaneal
fractures fixed by transverse and axial screws.
AB - The management of displaced, intra-articular calcaneal fracture represents a
surgical challenge to even an experienced orthopedic surgeon. Plate
osteosynthesis using an extended lateral approach is complicated by soft tissue
problems, while those treated by closed reduction and percutaneous pinning cannot
address all the intra-articular fragments sufficiently. The objective of our
study is to evaluate restoration of subtalar joint and long-term functional
outcomes in intra-articular displaced calcaneal fractures treated with transverse
subcondral screws through a small incision on lateral aspect of calcaneus and
percutaneously placed axial screws through the calcaneal tuberosity. Forty-five
intra-articular calcaneal fractures were managed with this minimally invasive
technique. Calcaneal height, width, length, Bohler's angle, and Gissane angle
were measured preoperatively and last follow-up visit. Functional outcomes were
assessed on the basis of American Orthopedic Foot and Ankle Society (AOFAS)
ankle/hind foot score. Preoperative calcaneal length, height, width, Bohler's
angle, and Gissane angle were improved from 68.62 +/- 2.64 to 72.44 +/- 2.63 mm,
39.28 +/- 2.72 to 32.37 +/- 2.65 mm, 47.04 +/- 2.56 to 49.55 +/- 2.45 mm, 12.66
degrees +/- 2.86 degrees to 26.93 degrees +/- 2.57 degrees , 123.91 degrees
+/- 3.13 degrees to 96.06 degrees +/- 3.92 degrees , respectively, after
surgery with P value <0.001. There were 21 (46.7%) excellent, 17 (37.8%) good, 4
(8.8%) fair, and 3 (6.7%) poor outcomes based on AOFAS ankle/hindfoot scores.
Time to unite the fracture was 11.06 +/- 1.82 weeks (range 8-16 weeks), and all
fractures were united without major complications. Minimally invasive technique
through a small incision on lateral aspect of calcaneus gives a moderately good
exposure for anatomical restoration of Sander's type II and III calcaneal
fractures fixed with both transverse and axial screws under fluoroscopic
guidance.
PMID- 28501962
TI - Arthrodesis of the thumb carpometacarpal joint using a quadrangular plate:
surgical technique and long-term results of 70 patients.
AB - PURPOSE: To assess the long-term results of trapeziometacarpal arthrodesis using
a quadrangular plate, regarding clinical, radiological and functional outcomes,
as well as development of complications. MATERIAL AND METHOD: From 2005 to 2015,
70 patients were treated at our institution for primary osteoarthrosis of thumb
carpometacarpal joint performing a trapeziometacarpal arthrodesis. A total of 85
arthrodesis were carried out using a titanium quadrangular plate (Proflyle plate,
Stryker(r), Kalamazoo MI, USA), without grafting in any case. Pre- and
postoperative functional data were assessed at the outpatient clinics using DASH,
MWS and VAS. All patients were asked for their ability to perform basic daily
activities before and after surgery. All patients were also asked about
satisfaction and their return to their jobs after surgery. Pre- and postoperative
radiological data were also assessed. RESULTS: There were 59 females and 11 males
with an average age of 55 years (range 44-60). In 66 cases arthrodesis was
carried out in the dominant hand, in 45 cases the right thumb was involved, and
in 40 the left thumb was involved; in 15 cases arthrodesis was carried out
bilaterally. Preoperative average DASH score was 64 (range 50-85), postoperative
average score was 25 (range 5-61). Regarding MWS, 51 patients obtained excellent
results, 15 patients obtained good results and 4 patients referred poor results.
The preoperative average score of VAS was 6 (range 5-10), which decrease to an
average of 2 (range 0-3) after surgery; all those differences were statistically
significant. All patients reported a mild loss of motion; however, all of them
reported improvement to carry out daily activities. There were four cases of
nonunion because of failure of fixation and two cases with dysesthetic scar.
There was no development of osteoarthritis in adjacent joints. The average follow
up was 60 months. CONCLUSIONS: The use of quadrangular plates for arthrodesis of
the trapeziometacarpal joint is a safety and reproducible technique with a low
rate of complications. Arthrodesis decreases pain and improves function in
patients with primary osteoarthritis of the thumb carpometacarpal joint; in spite
of a mild loss of motion, patients are satisfied with this procedure.
PMID- 28501961
TI - Risk factors for local recurrence from atypical cartilaginous tumour and
enchondroma of the long bones.
AB - INTRODUCTION: The purpose of our study is to verify possible clinical and
radiological findings with regard to distinguishing enchondroma from atypical
cartilaginous tumour (ACT). In addition, this study determined risk factors that
are associated with local recurrence of enchondroma or ACT treated with
curettage. MATERIALS AND METHODS: We retrospectively reviewed the records of 54
patients with enchondroma and 35 patients with ACT of the long bones treated by
curettage between 1986 and 2015. The minimum follow-up was 18 months. The
relationship between clinical and radiological factors and the tumour type or
local recurrence was assessed using Chi-square test or Fischer exact test.
RESULTS: Endosteal scalloping (p = 0.004) and soft tissue extension (p = 0.017)
were shown to statistically favour ACT over enchondroma; by contrast, pain (p =
0.034) was more frequent in enchondroma compared to ACT. All patients with
enchondroma had no local recurrence; in contrast, local recurrence occurred in
four patients with ACT (11%). Soft tissue extension (p = 0.049) and the diagnosis
of ACT (p = 0.021) were associated with an increased risk of local recurrence. We
had a disease progression in three of four patients with local recurrence, and
these had higher histological grade than the original tumour. DISCUSSION: Our
data show that endosteal scalloping and soft tissue extension could be helpful in
the differential diagnosis between enchondroma and ACT. We suggest following only
those patients with ACT after surgery to identify any possible recurrence and, in
case of recurrence, treat these patients with resection for the risk of disease
progression.
PMID- 28501963
TI - Salinity-driven decadal changes in phytoplankton community in the NW Arabian Gulf
of Kuwait.
AB - Evaluation of hydrological data obtained between 2000 and 2013 from a time series
station in Kuwait Bay (station K6) and an offshore southern location (station 18)
off Kuwait showed drastic increase in salinity by 6 units. We tested the
hypothesis that increased salinity impacted phytoplankton community
characteristics in these semiarid waters. The Arabian Gulf receives seasonal
freshwater discharge in the north via Shatt Al-Arab estuary with a peak during
March-July. A north to south gradient in the proportion of the freshwater exists
between station A in the vicinity of Shatt Al-Arab estuary and station 18 in the
southern offshore area. At station A, the proportion of freshwater was the
highest (25.6-42.5%) in 1997 but decreased to 0.8-4.6% by 2012-2013. The
prevailing hyperhaline conditions off Kuwait are attributed to decrease in the
river flow. Phytoplankton data showed a decrease in the number of constituent
taxa in the last one decade from 353 to 159 in the Kuwait Bay and from 164 to 156
in the offshore area. A shift in their biomass was caused by a decrease in diatom
species from 243 to 92 in the coastal waters and from 108 to 83 in the offshore
areas with a concomitant increase of smaller algae. Mutivariate agglomerative
hierarchical cluster analysis, non-metric multi-dimensional scaling, and one-way
analysis of similarity analyses on phytoplankton data at different taxonomic
levels confirmed significant changes in their community organization on a decadal
scale. These evidences support our hypothesis that the salinity-related
environmental changes have resulted in a coincidental decrease in species
diversity and significant changes in phytoplankton community between the years
2000-2002 and 2012-2013, off Kuwait. This in turn would affect the pelagic
trophodynamics as evident from a drastic decrease in the catch landings of
Tenulosa ilisha (Suboor), Carangoides sp. (Hamam), Otolithes ruber (Nowaiby),
Parastromateus niger (Halwaya), and Epinephelus coioides (Hamoor) in Kuwait.
PMID- 28501965
TI - Using a "Positive Deviance" Framework to Discover Adaptive Risk Reduction
Behaviors Among High-Risk HIV Negative Black Men Who Have Sex with Men.
AB - Despite the high incidence of HIV among young Black MSM in the United States and
engagement in high risk behaviors, many men in this group avoid infection. This
suggests that some men may engage in systematic risk reduction behaviors when not
always using condoms or abstaining from substances. Using a "positive deviance"
framework, we conducted qualitative interviews with HIV-negative, Black MSM
between 25 and 35 who reported unprotected anal sex and drug use in the past six
months or current heavy drinking (N = 29) to discover behaviors that could
facilitate remaining HIV-uninfected. Findings showed that MSM who remain HIV
negative despite continuing to engage in high-risk behaviors may be engaging in
adaptive risk reduction behaviors that, through successive decisions and advance
planning along the timeline to a sexual event, could lead to increased condom
use, avoidance or delay of a risky sexual event, or reduction of HIV positive
partners.
PMID- 28501964
TI - Consensus statement: Supporting Safer Conception and Pregnancy For Men And Women
Living with and Affected by HIV.
AB - Safer conception interventions reduce HIV incidence while supporting the
reproductive goals of people living with or affected by HIV. We developed a
consensus statement to address demand, summarize science, identify information
gaps, outline research and policy priorities, and advocate for safer conception
services. This statement emerged from a process incorporating consultation from
meetings, literature, and key stakeholders. Three co-authors developed an outline
which was discussed and modified with co-authors, working group members, and
additional clinical, policy, and community experts in safer conception, HIV, and
fertility. Co-authors and working group members developed and approved the final
manuscript. Consensus across themes of demand, safer conception strategies, and
implementation were identified. There is demand for safer conception services.
Access is limited by stigma towards PLWH having children and limits to provider
knowledge. Efficacy, effectiveness, safety, and acceptability data support a
range of safer conception strategies including ART, PrEP, limiting condomless sex
to peak fertility, home insemination, male circumcision, STI treatment, couples
based HIV testing, semen processing, and fertility care. Lack of guidelines and
training limit implementation. Key outstanding questions within each theme are
identified. Consumer demand, scientific data, and global goals to reduce HIV
incidence support safer conception service implementation. We recommend that
providers offer services to HIV-affected men and women, and program
administrators integrate safer conception care into HIV and reproductive health
programs. Answers to outstanding questions will refine services but should not
hinder steps to empower people to adopt safer conception strategies to meet
reproductive goals.
PMID- 28501966
TI - From method to hermeneutics: which epistemological framework for narrative
medicine?
AB - The past 10 years have seen considerable developments in the use of narrative in
medicine, primarily through the emergence of the so-called narrative medicine. In
this article, I question narrative medicine's self-understanding and contend that
one of the most prominent issues is its lack of a clear epistemological
framework. Drawing from Gadamer's work on hermeneutics, I first show that
narrative medicine is deeply linked with the hermeneutical field of knowledge.
Then I try to identify which claims can be legitimately expected from narrative
medicine, and which ones cannot be. I scrutinize in particular whether narrative
medicine can legitimately grasp the patient's lived experience of his or her
illness. In the last section of this article, I begin to explore the potential
usefulness of this epistemological clarification. This analysis allows for a
further understanding of what is really at stake with narrative medicine, and
thus to identify when it may be convenient, and when it may not. Furthermore,
this clarification opens up promising new possibilities of dialogue with critics
of the field. I conclude that narrative medicine finds its proper place as a
possible tool available to mediate dialogue, which is at the heart of the
clinical encounter in medical practice.
PMID- 28501967
TI - Plaque Tissue Morphology-Based Stroke Risk Stratification Using Carotid
Ultrasound: A Polling-Based PCA Learning Paradigm.
AB - Severe atherosclerosis disease in carotid arteries causes stenosis which in turn
leads to stroke. Machine learning systems have been previously developed for
plaque wall risk assessment using morphology-based characterization. The
fundamental assumption in such systems is the extraction of the grayscale
features of the plaque region. Even though these systems have the ability to
perform risk stratification, they lack the ability to achieve higher performance
due their inability to select and retain dominant features. This paper introduces
a polling-based principal component analysis (PCA) strategy embedded in the
machine learning framework to select and retain dominant features, resulting in
superior performance. This leads to more stability and reliability. The automated
system uses offline image data along with the ground truth labels to generate the
parameters, which are then used to transform the online grayscale features to
predict the risk of stroke. A set of sixteen grayscale plaque features is
computed. Utilizing the cross-validation protocol (K = 10), and the PCA cutoff of
0.995, the machine learning system is able to achieve an accuracy of 98.55 and
98.83%corresponding to the carotidfar wall and near wall plaques, respectively.
The corresponding reliability of the system was 94.56 and 95.63%, respectively.
The automated system was validated against the manual risk assessment system and
the precision of merit for same cross-validation settings and PCA cutoffs are
98.28 and 93.92%for the far and the near wall, respectively.PCA-embedded
morphology-based plaque characterization shows a powerful strategy for risk
assessment and can be adapted in clinical settings.
PMID- 28501968
TI - Effect of Parachute Jump in the Psychophysiological Response of Soldiers in Urban
Combat.
AB - The study of organic and psychological response during combat situations has been
poorly reported despite its importance for soldiers training and specific
instruction, so it was proposed as aim of the present investigation to analyze
the effect of a tactical parachute simulated jump in psycho-physiological
response of paratroopers' warfighters during an urban combat simulation. 19 male
paratroopers (31.9 +/- 6.2 year old; 173.6 +/- 5.3 cm; 73.8 +/- 8.3 Kg) of the
Spanish Army were divided in two groups: parachute jump group (n:11) that
conducted a simulated parachute jump and a urban combat maneuver and a non
parachute jump group (n:8) that only conducted an urban combat maneuver. We
analyzed before and after the maneuver the rated perceived exertion, legs
strength manifestation, blood lactate, cortical activation, heart rate
variability, blood oxygen saturation and pressure, skin temperature, fine motor
skills, and anxiety state. A tactical parachute simulated jump prior to an urban
combat maneuver produce significantly (p < 0.05) higher heart rate and decrease
in specific fine motor skills in comparison with no jump situation in
professional Army paratroopers. Independently of the parachute jump, an urban
combat maneuver produces a significant increase in rated perceived exertion,
blood lactate, heart rate, legs strength, sympathetic modulation and anxiety
response as well as a significant decrease in blood oxygen saturation and
parasympathetic modulation.
PMID- 28501970
TI - Cancer Center Volume and Type Impact Stage-Specific Utilization of Neoadjuvant
Therapy in Rectal Cancer.
AB - BACKGROUND: Neoadjuvant chemoradiation reduces local recurrence in locally
advanced rectal cancer, and adherence to national and societal recommendations
remains unknown. OBJECTIVE: To determine variability in guideline adherence in
rectal cancer treatment and investigate whether hospital volume correlated with
variability seen. DESIGN: We performed a retrospective analysis using the
National Cancer Database rectal cancer participant user files from 2005 to 2010.
Stage-specific predictors of neoadjuvant chemotherapy and radiation use were
determined, and variation in use across hospitals analyzed. Hospitals were ranked
based on likelihood of preoperative therapy use by stage, and observed-to
expected ratios for neoadjuvant therapy use calculated. Hospital outliers were
identified, and their center characteristics compared. RESULTS: A total of 23,488
patients were identified at 1183 hospitals. There was substantial variability in
the use of neoadjuvant chemoradiation across hospitals. Patients managed outside
clinical guidelines for both stage 1 and stage 3 disease tended to receive
treatment at lower-volume, community cancer centers. CONCLUSIONS: There is
substantial variability in adherence to national guidelines in the use of
neoadjuvant chemoradiation for rectal cancer across all stages. Both hospital
volume and center type are associated with over-treatment of early-stage tumors
and under-treatment of more invasive tumors. These findings identify a clear need
for national quality improvement efforts in the treatment of rectal cancer.
PMID- 28501969
TI - Chronic Pancreatitis: Current Status and Challenges for Prevention and Treatment.
AB - This paper reviews the current status of our understanding of the epidemiology,
diagnosis, and management of the continuum of pancreatic diseases from acute and
recurrent acute pancreatitis to chronic pancreatitis and the diseases that are
often linked with pancreatitis including diabetes mellitus and pancreatic cancer.
In addition to reviewing the current state of the field, we identify gaps in
knowledge that are necessary to address to improve patient outcomes in these
conditions.
PMID- 28501972
TI - Genetic variation of major histocompatibility complex genes in the endangered red
crowned crane.
AB - Populations that have drastically decreased in the past often have low genetic
variation, which may increase the risk of extinction. The genes of major
histocompatibility complex (MHC) play an important role in the adaptive immune
response of jawed vertebrates. Maintenance of adaptive genetic diversity such as
that of MHC genes is important for wildlife conservation. Here, we determined
genotypes of exon 3 of MHC class IA genes (MHCIA) and exon 2 of MHC class IIB
genes (MHCIIB) to evaluate genetic variation of the endangered red-crowned crane
population on Hokkaido Island, Japan, which experienced severe population decline
in the past. We identified 16 and 6 alleles of MHCIA and MHCIIB, respectively,
from 152 individuals. We found evidence of a positive selection at the antigen
binding sites in MHCIA exon 3 and MHCIIB exon 2. The phylogenetic analyses
indicated evidence of trans-species polymorphism among the crane MHC genes. The
genetic variability in both classes of MHC genes at the population level was low.
No geographic structure was found based on the genetic diversity of
microsatellite and MHC genes. Our study provides useful data for the optimal
management of the red-crowned crane population in Hokkaido and can contribute to
future studies on MHC genes of the continental populations of the red-crowned
crane and other crane species.
PMID- 28501973
TI - Neuroprotective compounds from Reynoutria sachalinensis.
AB - Glutamate is a neurotransmitter in central nervous system. Overexpression of
glutamate leads to oxidative stress, resulting in several neurodegenerative
disorders that include Alzheimer's disease. The n-hexane fraction of stems and
ethyl acetate (EtOAc) fraction of flowers of Reynoutria sachalinensis provide
neuroprotection against glutamate-induced oxidative toxicity in HT22 cells. In
this study, 1-decanol (1), beta-amyrin (2), dammaran-3beta-ol (3), campesterol
(4), daucosterol (5), ergosterol peroxide (6), emodin 8-O-beta-D-glucopyranoside
(7), quercetin (8) and isoquercitrin (9) were isolated from n-hexane fractions of
stems and EtOAc fractions of flowers of R. sachalinensis. Their neuroprotective
activity was evaluated by MTT assay. 1-Decanol, campesterol, ergosterol peroxide,
quercetin and isoquercitrin exhibited neuroprotective activity. These compounds
decreased reactive oxygen species level, showed anti-oxidant activity with DPPH
radical and in a H2O2 scavenging assay. Therefore, the neuroprotective activity
of 1-decanol, campesterol, ergosterol peroxide, quercetin and isoquercitrin are
associated with antioxidant activity.
PMID- 28501971
TI - Electrolyte and Acid-Base Disturbances in End-Stage Liver Disease: A
Physiopathological Approach.
AB - Electrolyte and acid-base disturbances are frequent in patients with end-stage
liver disease; the underlying physiopathological mechanisms are often complex and
represent a diagnostic and therapeutic challenge to the physician. Usually, these
disorders do not develop in compensated cirrhotic patients, but with the onset of
the classic complications of cirrhosis such as ascites, renal failure,
spontaneous bacterial peritonitis and variceal bleeding, multiple electrolyte,
and acid-base disturbances emerge. Hyponatremia parallels ascites formation and
is a well-known trigger of hepatic encephalopathy; its management in this
particular population poses a risky challenge due to the high susceptibility of
cirrhotic patients to osmotic demyelination. Hypokalemia is common in the setting
of cirrhosis: multiple potassium wasting mechanisms both inherent to the disease
and resulting from its management make these patients particularly susceptible to
potassium depletion even in the setting of normokalemia. Acid-base disturbances
range from classical respiratory alkalosis to high anion gap metabolic acidosis,
almost comprising the full acid-base spectrum. Because most electrolyte and acid
base disturbances are managed in terms of their underlying trigger factors, a
systematic physiopathological approach to their diagnosis and treatment is
required.
PMID- 28501974
TI - Proteolytic activities in cortex of apical parts of Vicia faba ssp. minor
seedling roots during kinetin-induced programmed cell death.
AB - Programmed cell death (PCD) is a crucial process in plant development. In this
paper, proteolytically related aspects of kinetin-induced PCD in cortex cells of
Vicia faba ssp. minor seedlings were examined using morphological, fluorometric,
spectrophotometric, and fluorescence microscopic analyses. Cell viability
estimation after 46 MUM kinetin treatment of seedling roots showed that the
number of dying cortex cells increased with treatment duration, reaching maximum
after 72 h. Weight of the apical root segments increased with time and was about
2.5-fold greater after 96 h, while the protein content remained unchanged,
compared to the control. The total and cysteine-dependent proteolytic activities
fluctuated during 1-96-h treatment, which was not accompanied by the changes in
the protein amount, indicating that the absolute protein amounts decreased during
kinetin-induced PCD. N-ethylmaleimide (NEM), phenylmethylsulfonyl fluoride
(PMSF), and Z-Leu-Leu-Nva-H (MG115), the respective cysteine, serine, and
proteasome inhibitors, suppressed kinetin-induced PCD. PMSF significantly
decreased serine-dependent proteolytic activities without changing the amount of
proteins, unlike NEM and MG115. More pronounced effect of PMSF over NEM indicated
that in the root apical segments, the most important proteolytic activity during
kinetin-induced PCD was that of serine proteases, while that of cysteine
proteases may be important for protein degradation in the last phase of the
process. Both NEM and PMSF inhibited apoptotic-like structure formation during
kinetin-induced PCD. The level of caspase-3-like activity of beta1 proteasome
subunit increased after kinetin treatment. Addition of proteasome inhibitor MG
115 reduced the number of dying cells, suggesting that proteasomes might play an
important role during kinetin-induced PCD.
PMID- 28501975
TI - Changes in liver perfusion and function before and after percutaneous occlusion
of spontaneous portosystemic shunt.
AB - PURPOSE: To evaluate changes in liver perfusion after occlusion of spontaneous
portosystemic shunt and to analyze mechanisms of liver profile improvement.
MATERIALS AND METHODS: Liver function changes and portal venous and hepatic
arterial blood flow were evaluated using perfusion CT before and after shunt
occlusion in 23 patients who underwent percutaneous occlusion of spontaneous
portosystemic shunt because of gastric varices (n = 15) or hepatic encephalopathy
(n = 8). RESULTS: Portal venous blood flow was significantly higher at 1 week
(278.7 ml/min, 92.7-636.7, p = 0.012), 1 month (290.0 ml/min, 110.1-560.1, p <
0.001) and 3 months (299.6 ml/min, 156.7-618.5, p = 0.033) after shunt occlusion
than the baseline (220.9 ml/min, 49.5-566.7). Hepatic arterial liver blood flow
became lower than the baseline (132.3 ml/min, 47.9-622.3) after shunt occlusion,
but a significant decrease was observed only at 1 month later (107.9 ml/min, 45.8
263.6 p = 0.027). Serum albumin concentration became significantly higher than
the baseline (3.4 mg/dl, 1.9-4.5) at 1 month (3.8 mg/dl, 2.3-4.3, p = 0.018) and
3 months (3.9 mg/dl, 2.6-4.3, p = 0.024) after shunt occlusion. CONCLUSION: Shunt
occlusion increases portal venous blood flow and decreases hepatic arterial blood
flow, thereby improving the liver profile.
PMID- 28501976
TI - Component Resolved Diagnosis in Hymenoptera Anaphylaxis.
AB - PURPOSE OF REVIEW: Hymenoptera anaphylaxis is one of the leading causes of severe
allergic reactions and can be fatal. Venom-specific immunotherapy (VIT) can
prevent a life-threatening reaction; however, confirmation of an allergy to a
Hymenoptera venom is a prerequisite before starting such a treatment. Component
resolved diagnostics (CRD) have helped to better identify the responsible
allergen. RECENT FINDINGS: Many new insect venom allergens have been identified
within the last few years. Commercially available recombinant allergens offer new
diagnostic tools for detecting sensitivity to insect venoms. Additional added
sensitivity to nearly 95% was introduced by spiking yellow jacket venom (YJV)
extract with Ves v 5. The further value of CRD for sensitivity in YJV and honey
bee venom (HBV) allergy is more controversially discussed. Recombinant allergens
devoid of cross-reactive carbohydrate determinants often help to identify the
culprit venom in patients with double sensitivity to YJV and HBV. CRD identified
a group of patients with predominant Api m 10 sensitization, which may be less
well protected by VIT, as some treatment extracts are lacking this allergen. The
diagnostic gap of previously undetected Hymenoptera allergy has been decreased
via production of recombinant allergens. Knowledge of analogies in interspecies
proteins and cross-reactive carbohydrate determinants is necessary to distinguish
relevant from irrelevant sensitizations.
PMID- 28501977
TI - Characterization of mitochondrial prohibitin from Boleophthalmus pectinirostris
and evaluation of its possible role in spermatogenesis.
AB - Prohibitin (PHB) is an evolutionarily conserved mitochondrial membrane protein.
It plays a vital role in cell proteolysis, senescence, and apoptosis and is
associated with spermatogenesis and sperm quality control in mammals. To study
the characteristics of the PHB gene and its potential roles during
spermatogenesis in Boleophthalmus pectinirostris, we cloned a 1153-bp full-length
cDNA from the testis of B. pectinirostris with an open reading frame of 816 bp,
which encodes 272 amino acid residues. Real-time quantitative PCR (qPCR) analysis
revealed the presence of phb mRNA in all the tissues examined, with higher
expression levels found in the testis, kidney, intestine, and muscle tissues. We
examined the localization of phb mRNA during spermatogenesis by in situ
hybridization (ISH), showing that phb mRNA was distributed in the periphery of
the nucleus in primary and secondary spermatocytes. In spermatid and mature
sperm, the phb mRNA gradually moved toward one side, where the flagellum is
formed. Immunofluorescence (IF) results showed co-localization of the PHB and
mitochondria at different stages during spermatogenesis of B. pectinirostris. The
signals obtained for PHB decreased as spermatogenesis proceeded; the strongest
detection signal was found in secondary spermatocytes, with lower levels of
staining in other stages. Additionally, in the mature germ cells, the PHB signals
were weak and aggregate in the midpiece of the flagellum.
PMID- 28501978
TI - Growth performance, oxidative stress, and non-specific immune responses in
juvenile sablefish, Anoplopoma fimbria, by changes of water temperature and
salinity.
AB - Juvenile sablefish, Anoplopoma fimbria (mean length 15.5 +/- 1.9 cm, mean weight
68.5 +/- 4.8 g), were used to evaluate the effects on growth, oxidative stress,
and non-specific immune responses by changes of water temperature (8, 10, 12, 14,
16, 18, and 20 degrees C) and salinity (100 (35.0), 90 (31.5), 80 (28.0), 70
(24.5), 60 (21.0), 50 (17.5), and 40% (14.0) (0/00)) for 4 months. The growth
performance was significantly increased at the temperature of 12 and 14 degrees
C, and the feed efficiency was notably decreased at the temperature of 18
degrees C. The growth performance and feed efficiency were also significantly
decreased at low salinity. The antioxidant responses such as superoxide dismutase
and catalase were significantly increased by the high temperature and decreased
by the low salinity. The immune responses such as lysozyme and phagocytosis were
elevated by the temperature of 18 degrees C and decreased by the salinity of
50%. The results of this study indicate that the growth performance of juvenile
sablefish, A. fimbria, is influenced by the temperature and salinity, and the
excessive temperature and salinity levels can affect the antioxidant and immune
responses.
PMID- 28501979
TI - Endocrine cells producing peptide hormones in the intestine of Nile tilapia:
distribution and effects of feeding and fasting on the cell density.
AB - Endocrine cells (ECs) act as a luminal surveillance system responding to either
the presence or absence of food in the gut through the secretion of peptide
hormones. The aim of this study was to analyze the effects of feeding and fasting
on the EC peptide-specific distribution along the intestine of Nile tilapia. We
assessed the density of ECs producing gastrin (GAS), cholecystokinin-8 (CCK-8),
neuropeptide Y (NPY), and calcitonin gene-related peptide (CGRP) in nine segments
of the intestine using immunohistochemistry. Our results show that ECs
immunoreactive to CCK-8, GAS, NPY, and CGRP can be found along all the intestinal
segments sampled, from the midgut to hindgut, although differences in their
distribution along the gut were observed. Regarding nutrient status, we found
that the anterior segments of the midgut seem to be the main site responding to
luminal changes in Nile tilapia. The NPY+ and CGRP+ EC densities increased in the
fasted group, while the amount of CCK-8+ ECs were higher in the fed group. No
effects of fasting or feeding were found in the GAS+ EC densities. Changes in ECs
density were found only at the anterior segments of the intestine which may be
due to the correlation between vagus nerve anatomy, EC location, and peptide
turnover. Lastly, ECs may need to be considered an active cell subpopulation that
may adapt and respond to different nutrient status as stimuli. Due to the
complexity of the enteroendocrine system and its importance in fish nutrition,
much remains to be elucidated and it deserves closer attention.
PMID- 28501980
TI - Medical comorbidity of binge eating disorder: response.
PMID- 28501981
TI - Protective Effect of Gentianine, a compound from Du Huo Ji Sheng Tang, against
Freund's Complete Adjuvant-Induced Arthritis in Rats.
AB - The anti-inflammatory property of gentianine (GE) aroused our interest. To
investigate the effect of GE on Freund's complete adjuvant (FCA)-induced
arthritis in rats was the aim of this study. Adjuvant-induced arthritis (AA) was
induced by the administration of 0.1 ml FCA in the surface of hind paw.
Diclofenac sodium (DS) and Fasudil were administered as positive controls.
Downregulation of cytokines including interleukin-6 (IL-6), interleukin-1 beta
(IL-1beta), and tumor necrosis factor-alpha (TNF-alpha) revealed anti
inflammatory effect of GE, which was consisted with pathological conditions of
rat paws. In addition, western blot analysis revealed that GE could strikingly
suppressed the expressions of Rho/NF-kappaB signaling pathways as well as TGF
beta/smad-3 pathways. In conclusion, data indicated that GE might contribute to
treat arthritis as a potential therapeutic candidate.
PMID- 28501982
TI - Smartphone Applications for Hypertension Management: a Potential Game-Changer
That Needs More Control.
AB - PURPOSE OF THE REVIEW: This review article will summarize available data on
mobile applications for the management of hypertension, by highlighting their
potential for clinical use, the current limitations and the yet pending issues to
be addressed in future studies. RECENT FINDINGS: The number of available
applications related to arterial hypertension and their usage by smartphone
owners is constantly increasing. However, most applications lack standardization
and scientific validation, and security flaws could be an important, yet still
underrated, issue. Small studies showed that treatment strategies based on
telemonitoring of home blood pressure with mobile applications could improve
blood pressure control, but there are no data on strong outcomes and the high
heterogeneity of available studies severely limits the possibility of reaching a
definitive conclusion on the impact of such strategies. Smartphone applications
for arterial hypertension represent a great chance to improve management of this
condition. Results from small studies are promising, but there is a strong need
for large, long-term, well-designed clinical trials, before these potential
solutions might be reliably applied in real-life patients' care.
PMID- 28501986
TI - Cloning and characterization of WRKY gene homologs in Chieh-qua (Benincasa
hispida Cogn. var. Chieh-qua How) and their expression in response to fusaric
acid treatment.
AB - The WRKY transcription factors play an important role in plant resistance for
biotic and abiotic stresses. In the present study, we cloned 10 WRKY gene
homologs (CqWRKY) in Chieh-qua (Benincasa hispida Cogn. var. Chieh-qua) using the
rapid-amplification of cDNA ends (RACE) or homology-based cloning methods. We
characterized the structure of these CqWRKY genes. Phylogenetic analysis of these
sequences with cucumber homologs suggested possible structural conservation of
these genes among cucurbit crops. We examined the expression levels of these
genes in response to fusaric acid (FA) treatment between resistant and
susceptible Chieh-qua lines with quantitative real-time PCR. All genes could be
upregulated upon FA treatment, but four CqWRKY genes exhibited differential
expression between resistant and susceptible lines before and after FA
application. CqWRKY31 seemed to be a positive regulator while CqWRKY1, CqWRKY23
and CqWRKY53 were negative regulators of fusaric resistance. This is the first
report of characterization of WRKY family genes in Chieh-qua. The results may
also be useful in breeding Chieh-qua for Fusarium wilt resistance.
PMID- 28501984
TI - Pediatric Gynecologic Cancers.
AB - PURPOSE OF REVIEW: Three primary categories of gynecologic cancer are found in
pediatric and adolescent patients: stromal carcinomas including juvenile
granulosa cell tumors and Sertoli-Leydig cell tumors, rhabdomyosarcomas arising
from the vagina and cervix (sarcoma botryoides), and ovarian germ cell tumors
which comprise a wide range of histologies. These entities are rare and treatment
approaches have focused on decreasing late effects of chemotherapy treatment.
Here, we review presentation, histologic classifications, diagnosis, and
treatment recommendations for pediatric gynecologic cancers. RECENT FINDINGS:
Event-free and overall survival for these cancers is high, and the goals of
treatment are minimization of morbidity and preservation of fertility with
unilateral salpingo-oophorectomies and limited staging. Surveillance of tumor
markers after surgery is helpful in monitoring for disease progression and
adjuvant chemotherapy is often reserved for patients at recurrence. Recent
literature supports avoiding chemotherapy even in high-grade germ cell tumors in
the pediatric population.
PMID- 28501983
TI - Understanding the Two Faces of Low-Salt Intake.
AB - Fierce debate has developed whether low-sodium intake, like high-sodium intake,
could be associated with adverse outcome. The debate originates in earlier
epidemiological studies associating high-sodium intake with high blood pressure
and more recent studies demonstrating a higher cardiovascular event rate with
both low- and high-sodium intake. This brings into question whether we entirely
understand the consequences of high- and (very) low-sodium intake for the
systemic hemodynamics, the kidney function, the vascular wall, the immune system,
and the brain. Evolutionarily, sodium retention mechanisms in the context of low
dietary sodium provided a survival advantage and are highly conserved,
exemplified by the renin-angiotensin system. What is the potential for this
sodium-retaining mechanism to cause harm? In this paper, we will consider current
views on how a sodium load is handled, visiting aspects including the effect of
sodium on the vessel wall, the sympathetic nervous system, the brain renin
angiotensin system, the skin as "third compartment" coupling to vascular
endothelial growth factor C, and the kidneys. From these perspectives, several
mechanisms can be envisioned whereby a low-sodium diet could potentially cause
harm, including the renin-angiotensin system and the sympathetic nervous system.
Altogether, the uncertainties preclude a unifying model or practical clinical
guidance regarding the effects of a low-sodium diet for an individual. There is a
very strong need for fundamental and translational studies to enhance the
understanding of the potential adverse consequences of low-salt intake as an
initial step to facilitate better clinical guidance.
PMID- 28501987
TI - Effect of glucose and olive oil as potential carbon sources on production of PHAs
copolymer and tercopolymer by Bacillus cereus FA11.
AB - In this study, the influence of different physicochemical parameters on the yield
of polyhydroxyalkanoates (PHAs) produced by Bacillus cereus FA11 is investigated.
The physicochemical factors include pH, temperature, time, inoculum size and its
age, agitation speed and composition of the glucose rich peptone deficient (GRPD)
medium. During two-stage fermentation, B. cereus FA11 produced a significantly
high (p < 0.05) yield (80.59% w/w) of PHAs copolymer using GRPD medium containing
glucose (15 g/L) and peptone (2 g/L) at pH 7, 30 degrees C and 150 rpm after 48
h of incubation. On the other hand, the presence of olive oil (1% v/v) and
peptone (2 g/L) in the GRPD medium resulted in biosynthesis of tercopolymer
during two-stage fermentation and the yield of tercopolymer was 60.31% (w/w). The
purified PHAs was characterized by Fourier transform infrared spectroscopy and
proton resonance magnetic analysis. Proton resonance magnetic analysis confirmed
that the tercopolymer was comprised of three different monomeric subunits, i.e.,
3-hydroxybutyrate, 3-hydroxyvalerate and 6-hydroxyhexanoate.
PMID- 28501988
TI - Gluteus maximus contraction velocity assessed by tensiomyography improves
following arthroscopic treatment of femoroacetabular impingement.
AB - PURPOSE: Muscular impairment, particularly for the gluteus maximus (GM), has been
observed in femoroacetabular impingement (FAI). The purpose of this study was to
evaluate the tensiomyographic changes of the GM, rectus femoris (RF) and adductor
longus (AL) before and after arthroscopic surgery for FAI. It was hypothesized
that arthroscopic treatment of FAI would improve the preoperative muscular
impairment. METHODS: All patients undergoing arthroscopic treatment of FAI
between January and July 2015 were approached for eligibility. Patients included
had a tensiomyography (TMG) evaluation including maximal displacement (Dm) and
contraction time (Tc) of these muscles in both lower extremities. TMG values
between the injured and healthy sides were compared at the preoperative and post
operative (3, 6 and 12 months after surgery) periods. RESULTS: There were no
significant differences for the RF and AL, and Dm of the GM for any of the
comparisons (n.s.). However, GM Tc was significantly lower at 3 (p = 0.016), 6 (p
= 0.008), and 12 (p = 0.049) months after surgery in the injured side compared to
preoperatively. GM Tc of the healthy side was significantly lower than the
injured side at the preoperative period (p = 0.004) and at 3 (p = 0.024) and 6 (p
= 0.028) months after surgery, but these significant differences were no longer
observed at 12 months after surgery (n.s.). There was a significant reduction of
pain in the GM area at 1 year after surgery compared to preoperatively (p <
0.0001). CONCLUSIONS: Arthroscopic treatment of FAI and the subsequent
rehabilitation improves contraction velocity of the GM of the injured side.
Despite Tc is elevated in the GM of the injured compared to the healthy side
preoperatively and at 3 and 6 months after surgery, differences in Tc between
both sides are no longer significant at 12 months. Athletes with FAI
participating in sports with great involvement of GM may benefit from
arthroscopic treatment and its subsequent rehabilitation. TMG can be used as an
objective measurement to monitor muscular improvements of the GM after surgery in
these patients. LEVEL OF EVIDENCE: II.
PMID- 28501990
TI - Tumor Staging and Grading: A Primer.
AB - Cancer staging and grading are used to predict the clinical behavior of
malignancies, establish appropriate therapies, and facilitate exchange of precise
information between clinicians. The internationally accepted criterion for cancer
staging, the tumor-node-metastasis (TNM) system, includes: (1) tumor size and
local growth (T), (2) extent of lymph node metastases (N), and (3) occurrence of
distant metastases (M). Clinical stage is established before initiation of
therapy and is determined by physical examination, laboratory findings, and
imaging studies. Pathologic stage is determined following surgical exploration of
disease and histologic examination of tissue. The TNM classification system has
evolved over 70 years to accommodate increasing knowledge about cancer biology.
Molecular technologies such as genomic and proteomic profiling of tumors could
eventually be incorporated into the TNM staging system. This chapter describes
the current TNM system using breast, lung, ovarian, and prostate cancer examples.
PMID- 28501991
TI - Innovations in Clinical Trial Design in the Era of Molecular Profiling.
AB - Historically, cancer has been studied, and therapeutic agents have been evaluated
based on organ site, clinical staging, and histology. The science of molecular
profiling has expanded our knowledge of cancer at the cellular and molecular
level such that numerous subtypes are being described based on biomarker
expression and genetic mutations rather than traditional classifications of the
disease. Drug development has experienced a concomitant revolution in response to
this knowledge with many new targeted therapeutic agents becoming available, and
this has necessitated an evolution in clinical trial design. The traditional,
large phase II and phase III adjuvant trial models need to be replaced with
smaller, shorter, and more focused trials. These trials need to be more efficient
and adaptive in order to quickly assess the efficacy of new agents and develop
new companion diagnostics. We are now seeing a substantial shift from the
traditional multiphase trial model to an increase in phase II adjuvant and
neoadjuvant trials in earlier-stage disease incorporating surrogate endpoints for
long-term survival to assess efficacy of therapeutic agents in shorter time
frames. New trial designs have emerged with capabilities to assess more
efficiently multiple disease types, multiple molecular subtypes, and multiple
agents simultaneously, and regulatory agencies have responded by outlining new
pathways for accelerated drug approval that can help bring effective targeted
therapeutic agents to the clinic more quickly for patients in need.
PMID- 28501989
TI - Negative control of Candida albicans filamentation-associated gene expression by
essential protein kinase gene KIN28.
AB - The fungus Candida albicans can grow as either yeast or filaments, which include
hyphae and pseudohyphae, depending on environmental conditions. Filamentous
growth is of particular interest because it is required for biofilm formation and
for pathogenesis. Environmentally induced filamentous growth is associated with
expression of filamentation-associated genes, and both filamentous growth and
associated gene expression depend upon several well-characterized transcription
factors. Surprisingly, strains with reduced expression of many essential genes
display filamentous growth under non-inducing conditions-those in which the wild
type grows as yeast. We found recently that diminished expression of several
essential protein kinase genes leads to both filamentous cell morphology and
filamentation-associated gene expression under non-inducing conditions. Reduced
expression of the essential protein kinase gene CAK1 promoted filamentation
associated gene expression and biofilm formation in strains that lacked key
transcriptional activators of these processes, thus indicating that CAK1
expression is critical for both environmental and genetic control of
filamentation. In this study, we extend our genetic interaction analysis to a
second essential protein kinase gene, KIN28. Reduced expression of KIN28 also
permits filamentation-associated gene expression, though not biofilm formation,
in the absence of several key transcriptional activators. Our results argue that
impairment of several essential cellular processes can alter the regulatory
requirements for filamentation-associated gene expression. Our results also
indicate that levels of filamentation-associated gene expression are not fully
predictive of biofilm formation ability.
PMID- 28501992
TI - Personalized Medicine: Ethical Aspects.
AB - In our time of genome-based personalized medicine, clinical research and clinical
medicine are accelerating at a quick pace. Faster and cheaper DNA sequencing and
protein profiling, microfluidic devices for capturing blood biomarkers,
nanoparticles for precise drug delivery and enhanced imaging, rapid computational
analysis of massive data inputs, and other technological wonders coalesce to
create a kind of Moore's Law for medicine. Needs are obvious, knowledge grows,
capital becomes available, but these factors are not entirely sufficient to make
health more achievable. Personalized medicine also requires social acceptability,
not only for accuracy and efficacy but also because medicine is a moral domain.
This chapter deals with medical ethics that determine the choices a society makes
regarding healthcare; and it has not always been a steady, morally correct course
of progress. Indeed, medical ethics has largely derived from socio-scientific
calamities in the past. Personalized medicine, with its enhanced capacity to
access the individuality of illness, must have a continuously evolving feedback
mechanism-the most important element being the physician-patient relationship
which is its ethical footing.
PMID- 28501993
TI - Antibody Validation by Western Blotting.
AB - Validation of antibodies is an integral part of translational research,
particularly for biomarker discovery. Assaying the specificity of the reagent
(antibody) and confirming the identity of the protein biomarker is of critical
importance prior to implementing any biomarker in clinical studies, and the lack
of such quality control tests may result in unexpected and/or misleading
results.Antibody validation is the procedure in which a single antibody is
thoroughly assayed for sensitivity and specificity. Although a plethora of
commercial antibodies exist, antibody specificity must be extensively
demonstrated using diverse complex biological samples, rather than purified
recombinant proteins, prior to use in clinical translational research. In the
simplest iteration, antibody specificity is determined by the presence of a
single band in a complex biological sample, at the expected molecular weight, on
a Western blot.To date, numerous Western blotting procedures are available, based
on either manual or automated systems and spanning the spectrum of single blots
to multiplex blots. X-ray film is still employed in many research laboratories,
but digital imaging has become a gold standard in immunoblotting. The basic
principles of Western blotting are (a) separation of protein mixtures by gel
electrophoresis, (b) transfer of the proteins to a blot, (c) probing the blot for
a protein or proteins of interest, and (d) subsequent detection of the protein by
chemiluminescent, fluorescent, or colorimetric methods. This chapter focuses on
the chemiluminescent detection of proteins using a manual Western blotting system
and a vacuum-enhanced detection system (SNAP i.d.TM, Millipore).
PMID- 28501994
TI - Scanning Electron Microscopy Sample Preparation and Imaging.
AB - Scanning electron microscopes allow us to reach magnifications of 20-130,000* and
resolve compositional and topographical images with intense detail. These images
are created by bombarding a sample with electrons in a focused manner to generate
a black and white image from the electrons that bounce off of the sample. The
electrons are detected using positively charged detectors. Scanning electron
microscopy permits three-dimensional imaging of desiccated specimens or wet cells
and tissues by using variable pressure chambers. SEM ultrastructural analysis and
intracellular imaging supplement light microscopy for molecular profiling of
prokaryotes, plants, and mammals. This chapter demonstrates how to prepare and
image samples that are (a) desiccated and conductive, (b) desiccated and
nonconductive but coated with an electron conductive film using a gold sputter
coater, and
PMID- 28501995
TI - One-Step Preservation and Decalcification of Bony Tissue for Molecular Profiling.
AB - Bone metastasis from primary cancer sites creates diagnostic and therapeutic
challenges. Calcified bone is difficult to biopsy due to tissue hardness and
patient discomfort, thus limiting the frequency and availability of bone/bone
marrow biopsy material for molecular profiling. In addition, bony tissue must be
demineralized (decalcified) prior to histomorphologic analysis. Decalcification
processes rely on three main principles: (a) solubility of calcium salts in an
acid, such as formic or nitric acid; (b) calcium chelation with
ethylenediaminetetraacetic acid (EDTA); or (c) ion-exchange resins in a weak
acid. A major roadblock in molecular profiling of bony tissue has been the lack
of a suitable demineralization process that preserves histomorphology of
calcified and soft tissue elements while also preserving phosphoproteins and
nucleic acids. In this chapter, we describe general issues relevant to specimen
collection and preservation of osseous tissue for molecular profiling. We provide
two protocols: (a) one-step preservation of tissue histomorphology and proteins
and posttranslational modifications, with simultaneous decalcification of bony
tissue, and (b) ethanol-based tissue processing for TheraLin-fixed bony tissue.
PMID- 28501996
TI - Application of Hydrogel Nanoparticles for the Capture, Concentration, and
Preservation of Low-Abundance Biomarkers.
AB - In the recent years, a lot of emphasis has been placed on the discovery and
detection of clinically relevant biomarkers. Biomarkers are crucial for the early
detection of several diseases, and they play an important role in the improvement
of current treatments, thus reducing patient mortality rate. Because biofluids
account to 60% of the body mass, they represent a goldmine of significant
biomarkers. Unfortunately, because of their low concentration in body fluids,
their lability, and the presence of high abundance proteins (i.e., albumin and
immunoglobulins), low abundance biomarkers are difficult to detect with mass
spectrometry or immunoassays. Nanoparticles made of poly(N-isopropylacrylamide)
(NIPAm) and functionalized with affinity reactive baits allow researchers to
overcome these physiological barriers and in one single step capture,
concentrate, and preserve labile biomarkers in complex body fluids (i.e. urine,
blood, sweat, CSF). Although hydrogel nanoparticles have been largely studied and
used as a drug delivery tool, our application focuses on their capturing
abilities instead of the releasing of specific drug molecules. Once the
functionalized nanoparticles are incubated with a biological fluid, small
biomarkers are captured by the affinity baits while unwanted high abundance
analytes are excluded. The potentially relevant biomarkers are then concentrated
into small volumes. The concentration factor (up to 10,000-fold) successfully
enhances the detection sensitivity of mass spectrometry and immunoassays allowing
the detection of previously invisible proteins.
PMID- 28501997
TI - Using Laser Capture Microdissection to Isolate Cortical Laminae in Nonhuman
Primate Brain.
AB - Laser capture microdissection (LCM) is a technique that allows procurement of an
enriched cell population from a heterogeneous tissue sample under direct
microscopic visualization. Fundamentally, laser capture microdissection consists
of three main steps: (1) visualizing the desired cell population by microscopy,
(2) melting a thermolabile polymer onto the desired cell populations using
infrared laser energy to form a polymer-cell composite (capture method) or
photovolatizing a region of tissue using ultraviolet laser energy (cutting
method), and (3) removing the desired cell population from the heterogeneous
tissue. In this chapter, we discuss the infrared capture method only. LCM
technology is compatible with a wide range of downstream applications such as
mass spectrometry, DNA genotyping and RNA transcript profiling, cDNA library
generation, proteomics discovery, and signal pathway mapping. This chapter
profiles the ArcturusXTTM laser capture microdissection instrument, using
isolation of specific cortical lamina from nonhuman primate brain regions, and
sample preparation methods for downstream proteomic applications.
PMID- 28501998
TI - Western Blot Techniques.
AB - The Western blot is an important laboratory technique that allows for specific
identification and characterization of proteins. Sodium dodecyl sulfate
polyacrylamide gel electrophoresis (SDS-PAGE)-separated proteins are
electophoretically transferred to a polyvinylidene fluoride (PVDF) membrane which
is then incubated with specific antibodies, then developed to show the protein of
interest. Here, we describe the transfer and detection of Outer surface protein A
(OspA), a protein only found on the surface of Borrelia burgdorferi, the bacteria
responsible for Lyme disease.
PMID- 28501999
TI - ELISA for Monitoring Nerve Growth Factor.
AB - Nerve growth factor (NGF), a neurotrophin critical to neuronal viability, has
become a popular research focus for the treatment of neurodegenerative diseases.
Enzyme-linked immunosorbent assays (ELISA) allow the quantification of cellular
proteins, such as NGF, secreted into conditioned culture media. However, off-the
shelf reagents and kit components may require optimization depending on the
specific specimens and/or antibodies that will be utilized with the ELISA assay.
Herein we describe a protocol for developing a sandwich ELISA, incorporating NGF
specific primary and secondary antibodies capable of detecting NGF at
concentrations as low as 10 pg/mL.
PMID- 28502000
TI - Reverse Phase Protein Microarrays.
AB - While genes and RNA encode information about cellular status, proteins are
considered the engine of the cellular machine, as they are the effective elements
that drive all cellular functions including proliferation, migration,
differentiation, and apoptosis. Consequently, investigations of the cellular
protein network are considered a fundamental tool for understanding cellular
functions.Alteration of the cellular homeostasis driven by elaborate intra- and
extracellular interactions has become one of the most studied fields in the era
of personalized medicine and targeted therapy. Increasing interest has been
focused on developing and improving proteomic technologies that are suitable for
analysis of clinical samples. In this context, reverse-phase protein microarrays
(RPPA) is a sensitive, quantitative, high-throughput immunoassay for protein
analyses of tissue samples, cells, and body fluids.RPPA is well suited for broad
proteomic profiling and is capable of capturing protein activation as well as
biochemical reactions such as phosphorylation, glycosylation, ubiquitination,
protein cleavage, and conformational alterations across hundreds of samples using
a limited amount of biological material. For these reasons, RPPA represents a
valid tool for protein analyses and generates data that help elucidate the
functional signaling architecture through protein-protein interaction and protein
activation mapping for the identification of critical nodes for individualized or
combinatorial targeted therapy.
PMID- 28502001
TI - Clustering and Network Analysis of Reverse Phase Protein Array Data.
AB - Molecular profiling of proteins and phosphoproteins using a reverse phase protein
array (RPPA) platform, with a panel of target-specific antibodies, enables the
parallel, quantitative proteomic analysis of many biological samples in a
microarray format. Hence, RPPA analysis can generate a high volume of
multidimensional data that must be effectively interrogated and interpreted. A
range of computational techniques for data mining can be applied to detect and
explore data structure and to form functional predictions from large datasets.
Here, two approaches for the computational analysis of RPPA data are detailed:
the identification of similar patterns of protein expression by hierarchical
cluster analysis and the modeling of protein interactions and signaling
relationships by network analysis. The protocols use freely available, cross
platform software, are easy to implement, and do not require any programming
expertise. Serving as data-driven starting points for further in-depth analysis,
validation, and biological experimentation, these and related bioinformatic
approaches can accelerate the functional interpretation of RPPA data.
PMID- 28502002
TI - PCR: Identification of Genetic Polymorphisms.
AB - Polymerase chain reaction (PCR) enables the amplification of a specific sequence
of deoxyribonucleic acid (DNA) through the process of three main steps: template
DNA denaturation, annealing of the primers to complementary sequences, and primer
extension to synthesize DNA strands. By using this method, the target sequence
will be copied and amplified at an exponential rate. PCR provides a qualitative
method for identifying DNA from fresh or dried cells/body fluids, formalin-fixed
archival tissue specimens, and ancient specimens.Herein we describe basic
information for performing successful PCR experiments using the amplification of
a human Alu insertion on the PV92 gene locus on chromosome 16 as an example
method.
PMID- 28502004
TI - Somatic DNA Mutation Analysis.
AB - Somatic mutations in patient tumor DNA samples can be readily detected based on
mass spectrometry. The MassARRAY system is a high-throughput matrix-assisted
laser desorption time-of-flight (MALDI) mass spectrometer for detection of
nucleic acids. The technique is based on single-nucleotide base extension. A
series of PCR assays amplify specific DNA regions of interest harboring
mutations. A third primer is then introduced into the reaction which corresponds
to the DNA template immediately in front of the mutation site. A final round of
PCR is then performed using mass-modified nucleotides. These nucleotides are
designed so that no additional bases can be added to the extension primer
(terminating bases) after a single-base extension and are mass modified to
exaggerate mass differences between nucleotides allowing easier identification by
mass spectrometry.The sequences of the extension primer and possible extension
products (wild type and mutations) are known; therefore, it is possible to
calculate their mass. The mass spectrometer can identify the mass peaks for each
assay and identify those with mutations (multiple peaks). The technique was
originally designed to screen multiple single-nucleotide polymorphisms (SNPs) in
a large number of specimens. A SNP in the coding region of DNA that alters the
gene and subsequent protein expression is considered a mutation. Mutations often
occur in genes whose protein product is in a key signaling pathway and/or drug
target. Rationale treatment options can be designed based upon the presence or
absence of these mutations. In this chapter, we describe the process for
detection of somatic mutations in DNA extracted from formalin-fixed paraffin
embedded (FFPE) material.
PMID- 28502003
TI - Microsatellite Analysis for Identification of Individuals Using Bone from the
Extinct Steller's Sea Cow (Hydrodamalis gigas).
AB - Microsatellite DNA can provide more detailed population genetic information than
mitochondrial DNA which is normally used to research ancient bone. The methods
detailed in this chapter can be utilized for any type of bone. However, for this
example, four microsatellite loci were isolated from Steller's sea cow
(Hydrodamalis gigas) using published primers for manatee and dugong
microsatellites. The primers DduC05 (Broderick et al., Mol Ecol Notes 6:1275
1277, 2007), Tmakb60, TmaSC5 (Pause et al., Mol Ecol Notes 6: 1073-1076, 2007),
and TmaE11 (Garcia-Rodriguez et al., Mol Ecol 12:2161-2163, 2000) all
successfully amplified microsatellites from H. gigas. The DNA samples were from
bone collected on Bering or St. Lawrence Islands. DNA was analyzed using primers
with the fluorescent label FAM-6. Sequenced alleles were then used to indicate a
difference in the number of repeats and thus a difference in individuals. This is
the first time that H. gigas microsatellite loci have been isolated. These
techniques for ancient bone microsatellite analysis allow an estimate of
population size for a newly discovered St. Lawrence Island sea cow population.
PMID- 28502005
TI - Optimization of Immunostaining for Prospective Image Analysis.
AB - Biomarker discovery is a crucial part of the fast developing field of
personalized medicine. Antibody-based techniques including immunostaining of
tissue samples are widely used for biomarker evaluation in preclinical and
clinical studies. When used in conjunction with robust image analysis methods, it
provides a powerful means to assess biomarker modulation, toxicity, and patient
response to targeted agents. Here, we describe the optimization of
immunofluorescent (IF) staining protocols and a sample IF multiplex protocol
suitable for colocalization image analysis.
PMID- 28502006
TI - Fluorescence In Situ Hybridization of Cells, Chromosomes, and Formalin-Fixed
Paraffin-Embedded Tissues.
AB - Fluorescence in situ hybridization (FISH) with DNA probes allows the
visualization of gene copy number and localization of specific DNA targets with
fluorescence microscopy. Cells in culture, metaphase chromosomes, and tissue
sections are fixed and prepared on glass slides. Both the DNA in the cells and
fluorescently labeled probe are denatured, and the labeled probe is allowed to
hybridize to the cellular DNA. The slides are washed, counterstained, and viewed
via fluorescence microscopy. We describe the basic method for preparing slides
and probes for studies involving DNA copy number changes and structural
chromosome rearrangements in formalin-fixed paraffin-embedded (FFPE) tissue
sections and cell culture preparations.
PMID- 28502007
TI - High-Resolution Image Stitching as a Tool to Assess Tissue-Level Protein
Distribution and Localization.
AB - High-resolution microscopy has traditionally come at the expense of field of
view, resulting in suboptimal interpretation of protein distribution throughout
large or complex samples. Likewise, a low-resolution microscopic approach
inhibits the ability of researchers to precisely localize proteins of interest at
the subcellular level. Until recently, the ability to combine the strengths of
these approaches was limited and technically impractical for most laboratories to
implement. Continued advances in microscope automation, sophisticated software
applications, and modern workstations have enabled expansion of such
combinatorial approaches to researchers outside computationally focused fields.
Through image stitching, researchers can acquire large field-of-view,
multidimensional datasets, at the diffraction limit of high-numerical aperture
objectives to effectively map protein distribution in large samples with high
precision. Here, we outline a protocol for acquisition of such datasets with the
purpose of introducing inexperienced researchers to the methodology of large
image stitching using the widely available technology of laser point-scanning
confocal microscopy in combination with basic microscope automation and freely
available software for post-acquisition processing.
PMID- 28502008
TI - Mass Spectrometry-Based Biomarker Discovery.
AB - The discovery of candidate biomarkers within the entire proteome is one of the
most important and challenging goals in proteomic research. Mass spectrometry
based proteomics is a modern and promising technology for semiquantitative and
qualitative assessment of proteins, enabling protein sequencing and
identification with exquisite accuracy and sensitivity. For mass spectrometry
analysis, protein extractions from tissues or body fluids and subsequent protein
fractionation represent an important and unavoidable step in the workflow for
biomarker discovery. Following extraction of proteins, the protein mixture must
be digested, reduced, alkylated, and cleaned up prior to mass spectrometry. The
aim of our chapter is to provide comprehensible and practical lab procedures for
sample digestion, protein fractionation, and subsequent mass spectrometry
analysis.
PMID- 28502009
TI - Quantitative Mass Spectrometry by Isotope Dilution and Multiple Reaction
Monitoring (MRM).
AB - Selected reaction monitoring (SRM) is used in molecular profiling to detect and
quantify specific known proteins in complex mixtures. Using isotope dilution
(Barnidge et al., Anal Chem 75(3):445-451, 2003) methodologies, peptides can be
quantified without the need for an antibody-based method. Selected reaction
monitoring assays employ electrospray ionization mass spectrometry (ESI-MS)
followed by two stages of mass selection: a first stage where the mass of the
peptide ion is selected and, after fragmentation by collision-induced
dissociation (CID), a second stage (tandem MS) where either a single (e.g., SRM)
or multiple (multiple reaction monitoring, MRM) specific peptide fragment ions
are transmitted for detection. The MRM experiment is accomplished by specifying
the parent masses of the selected endogenous and isotope-labeled peptides for
MS/MS fragmentation and then monitoring fragment ions of interest, using their
intensities/abundances and relative ratios to quantify the parent protein of
interest. In this example protocol, we will utilize isotope dilution MRM-MS to
quantify in absolute terms the total levels of the protein of interest, ataxia
telangiectasia mutated (ATM) serine/threonine protein kinase. Ataxia
telangiectasia mutated (ATM) phosphorylates several key proteins that initiate
activation of the DNA damage checkpoint leading to cell cycle arrest.
PMID- 28502010
TI - LC-Mass Spectrometry for Metabolomics.
AB - The field of metabolomics is greatly being refined by the addition of new
technologies. LC-MS has allowed researchers to explore additional metabolites
which were not originally captured through GC-MS. Through the customizability of
the LC columns and mass spectrometer, it is now easier to tailor the instrument
to your research needs. Herein, we describe a protocol for sample preparation and
data acquisition for a global metabolomic analysis of tissues or feces.
PMID- 28502011
TI - Metabolomic Bioinformatic Analysis.
AB - Metabolomics allows for the investigation of the small molecules found within
living systems. Based on the design of the experiments, it is not uncommon for
these analyses to include matrices of thousands of variables. In order to handle
such large datasets, many have turned to multivariate statistical analyses to
analyze and understand their data. Herein, we present protocols for using R to
analyze metabolomic data using some of the more common multivariate statistical
techniques.
PMID- 28502012
TI - Stable Isotope Quantitative N-Glycan Analysis by Liquid Separation Techniques and
Mass Spectrometry.
AB - Liquid phase separation analysis and subsequent quantitation remains a
challenging task for protein-derived oligosaccharides due to their inherent
structural complexity and diversity. Incomplete resolution or co-detection of
multiple glycan species complicates peak area-based quantitation and associated
statistical analysis when optical detection methods are used. The approach
outlined herein describes the utilization of stable isotope variants of commonly
used fluorescent tags that allow for mass-based glycan identification and
relative quantitation following separation by liquid chromatography (LC) or
capillary electrophoresis (CE). Comparability assessment of glycoprotein-derived
oligosaccharides is performed by derivatization with commercially available
isotope variants of 2-aminobenzoic acid or aniline and analysis by LC- and CE
mass spectrometry. Quantitative information is attained from the extracted ion
chromatogram/electropherogram ratios generated from the light and heavy isotope
clusters.
PMID- 28502013
TI - Grant Writing Tips for Translational Research.
AB - All investigators face the same challenge-the highly competitive nature of the
grant review process. Innovation alone is not enough to ensure grant-supported
funding. Applied clinical research requires a diverse, collaborative team of
investigators with specialized skills, a supportive clinical research
environment, and access to clinical material. Additionally, the lack of animal
models for many diseases and ethical limitations prevent direct mechanistic
experiments that are possible using in vitro systems or animal models. Therefore,
specific granting mechanisms and program initiatives target translational
research studies. This chapter provides grant writing tips and lists resources
that may prove helpful for new investigators seeking research funding in support
of translational research, biobanking, and research utilizing molecular
biomarkers.
PMID- 28502014
TI - Inventions and Patents: A Practical Tutorial.
AB - Patents are designed to protect and encourage creativity and innovation.
Patenting a biomedical discovery can be a requirement before a pharmaceutical
company or biotech entity will invest in the lengthy and capital-intensive drug
development and clinical trials necessary to achieve patient benefit. Although
scientists and clinicians are well versed in research publication requirements,
patent descriptions and claims are formatted in a manner quite different from a
research paper. Patents require (a) a series of logical statements clearly
delineating the boundaries of the novel aspects of the invention and (b)
sufficient disclosure of the invention so that it can be reproduced by others.
Patents are granted only for inventions that meet three conditions: novelty, non
obviousness, and usefulness. Recent changes to US patent law limit the scope of
patentable material. Products of nature such as nucleic acids and proteins, or
steps used to observe natural events, are no longer patent eligible. This chapter
provides basic guidelines and definitions for inventions, inventorship, and
patent filing which are summarized using a question and answer format.
PMID- 28502015
TI - Product Development and Commercialization of Diagnostic or Life Science Products
for Scientists and Researchers.
AB - Commercializing a diagnostic or life science product often encompasses different
goals than that of research and grant funding. There are several necessary steps,
and a strategy needs to be well defined in order to be successful. Product
development requires input from and between various groups within a company and,
for academia, outside entities. The product development stakeholder
groups/entities are research, marketing, development, regulatory, manufacturing,
clinical, safety/efficacy, and quality. After initial research and development,
much of the work in product development can be outsourced or jointly created
using public-private partnerships. This chapter serves as an overview of the
product development process and provides a guide to best define a product
strategy.
PMID- 28502016
TI - Correlation between in vitro and in vivo antimalarial activity of compounds using
CQ-sensitive and CQ-resistant strains of Plasmodium falciparum and CQ-resistant
strain of P. yoelii.
AB - Present efforts have been made to establish a correlation between in vitro and in
vivo antimalarial activity using MIC, IC50 and IC90 values against CQ-sensitive
(3D7) and CQ-resistant (K1) strains of Plasmodium falciparum and in vivo activity
against Plasmodium yoelii. The method of discriminant function analysis (DFA) was
applied to analyze the data. It was observed that in vitro IC90 values against
both 3D7 and K1 strains (p < 0.001) have strong correlation with in vivo curative
activity. The respective IC50 and IC90 values of compounds, which cured mice
(i.e., animals did not show recrudescence of parasitemia even after 60 days
posttreatment), ranged between 3 and 14 nM and 14 and 186 nM against 3D7 and
between 9 and 65 nM and 24 and 359 nM against the K1 strain of P. falciparum.
Whereas the IC50 and IC90 values of compounds which exhibited in vivo suppressive
activity in mice ranged between 10 and 307 nm and 61 and >965 nM, respectively,
against 3D7 and 75 and >806 nm and 241 and >1232 nM against the K1 strain of P.
falciparum. The findings suggest that IC90 values against both 3D7 and K1 strains
(p < 0.02) are the main contributors for the prediction of in vivo curative
activity of a new molecule. Apart from this, a reasonable correlation between MIC
and IC50 values of compounds has also been established.
PMID- 28502017
TI - Comparative analysis of immune effects in mice model: Clonorchis sinensis
cysteine protease generated from recombinant Escherichia coli and Bacillus
subtilis spores.
AB - Clonorchiasis remains a nonnegligible public health problem in endemic areas.
Cysteine protease of Clonorchis sinensis (CsCP) plays indispensable roles in the
parasitic physiology and pathology, and has been exploited as a promising drug
and vaccine candidate. In recent years, development of spore-based vaccines
against multiple pathogens has attracted many investigators' interest. In
previous studies, the recombinant Escherichia coli (BL21) and Bacillus subtilis
spores expressing CsCP have been successfully constructed, respectively. In this
study, the immune effects of CsCP protein purified from recombinant BL21 (rCsCP)
and B. subtilis spores presenting CsCP (B.s-CsCP) in Balb/c mice model were
conducted with comparative analysis. Levels of specific IgG, IgG1 and IgG2a were
significantly increased in sera from both rCsCP and B.s-CsCP intraperitoneally
immunized mice. Additionally, recombinant spores expressing abundant fusion CsCP
(0.03125 pg/spore) could strongly enhance the immunogenicity of CsCP with
significantly higher levels of IgG and isotypes. Compared with rCsCP alone,
intraperitoneal administration of mice with spores expressing CsCP achieved a
better effect of fighting against C. sinensis infection by slowing down the
process of fibrosis. Our results demonstrated that a combination of Th1/Th2
immune responses could be elicited by rCsCP, while spores displaying CsCP
prominently induced Th1-biased specific immune responses, and the complex
cytokine network maybe mediates protective immune responses against C. sinensis.
This work further confirmed that the usage of B. subtilis spores displaying CsCP
is an effective way to against C. sinensis.
PMID- 28502018
TI - Evolutionary processes in populations of Cryptosporidium inferred from gp60
sequence data.
AB - Cryptosporidiosis is one of the most common human infectious diseases globally.
The gp60 gene has been adopted as a key marker for molecular epidemiological
investigations into this protozoan disease because of the capability to
characterize genotypes and detect variants within Cryptosporidium species
infecting humans. However, we know relatively little about the potential spatial
and temporal variation in population demography that can be inferred from this
gene beyond that it is recognized to be under selective pressure. Here, we
analyzed the genetic variation in time and space within two putative populations
of Cryptosporidium in New Zealand to infer the processes behind the patterns of
sequence polymorphism. Analyses using Tajima's D, Fu, and Li's D* and F* tests
show significant departures from neutrality in some populations and indicate the
selective maintenance of alleles within some populations. Demographic analyses
showed distortions in the pattern of the genetic variability caused by high
recombination rates and population expansion, which was observed in case
notification data. Our results showed that processes acting on populations that
have similar effects can be distinguished from one another and multiple processes
can be detected acting at the same time. These results are significant for
prediction of the parasite dynamics and potential mechanisms of long-term changes
in the risk of cryptosporidiosis in humans.
PMID- 28502019
TI - A revision of the genus Aphalloides (Digenea: Cryptogonimidae), parasites of
European brackish water fishes.
AB - Trematodes of the genus Aphalloides Dollfus, Chabaud & Golvan, 1957 reach
maturity in their second intermediate host, small fishes of the family
Gobionellidae, genera Pomatoschistus and Knipowitschia. Two morphologically
similar species have been described from European waters: Aphalloides coelomicola
Dollfus et al., 1957 in the Mediterranean Sea (including the brackish Black Sea
region) and Aphalloides timmi Reimer, 1970 in the Baltic Sea. There was no
difference in morphology and morphometry for specimens corresponding to A.
coelomicola and A. timmi and examination of the 28S rDNA sequence confirmed the
similarity. Based on these results, these two species are synonymized and A.
coelomicola redescribed.
PMID- 28502020
TI - Biogeochemical zonation of sulfur during the discharge of groundwater to lake in
desert plateau (Dakebo Lake, NW China).
AB - As one of the important elements of controlling the redox system within the
hyporheic and hypolentic zone, sulfur is involved in a series of complex
biogeochemical processes such as carbon cycle, water acidification, formation of
iron and manganese minerals, redox processes of trace metal elements and a series
of important ecological processes. Previous studies on biogeochemistry of the
hyporheic and hypolentic zones mostly concentrated on nutrients of nitrogen and
phosphorus, heavy metals and other pollutants. Systematic study of biogeochemical
behavior of sulfur and its main controlling factors within the lake hypolentic
zone is very urgent and important. In this paper, a typical desert plateau lake,
Dakebo Lake in northwestern China, was taken for example within which redox
zonation and biogeochemical characteristics of sulfur affected by hydrodynamic
conditions were studied based on not only traditional hydrochemical analysis, but
also environmental isotope evidence. In the lake hypolentic zone of the study
area, due to the different hydrodynamic conditions, vertical profile of sulfur
species and environmental parameters differ at the two sites of the lake (western
side and center). Reduction of sulfate, deposition and oxidation of sulfide,
dissolution and precipitation of sulfur-bearing minerals occurred are responded
well to Eh, dissolved oxygen, pH, organic carbon and microorganism according to
which the lake hypolentic zone can be divided into reduced zone containing H2S,
reduced zone containing no H2S, transition zone and oxidized zone. The results of
this study provide valuable insights for understanding sulfur conversion
processes and sulfur biogeochemical zonation within a lake hypolentic zone in an
extreme plateau arid environment and for protecting the lake-wetland ecosystem in
arid and semiarid regions.
PMID- 28502022
TI - Is postural tachycardia syndrome in the head or in the heart? And other updates
on recent autonomic research.
PMID- 28502021
TI - The visual and haptic contributions to hand perception.
AB - Previous research has found that the perception of our hands is distorted. The
characteristics of this distortion are an overestimation of hand width and an
underestimation of finger length. The present study examined the role that
different sensory modalities (vision and/or haptics) play in the perception of
our hands. Participants pointed to their concealed hand in one of three groups:
Vision+Haptics, Vision-only, or Haptics-only. Participants in the Vision+Haptics
group had vision (non-informative) of the experimental setup and of the pointing
hand, but no vision of the hand being estimated. They also experienced haptic
feedback as the palm of the hand was in contact with the undersurface of a
tabletop, where the estimations were made. Participants in the Vision-only group,
instead of placing the hand to be estimated underneath the tabletop, they placed
it behind their backs. Participants in this group were asked to imagine as if the
hand was under the table when making their estimations. In the Haptics-only
group, participants completed the task with the hand underneath the tabletop (as
in the Vision+Haptics group) but did so while wearing a blindfold (no vision).
All participants estimated the position of ten landmarks on the hand: the
fingertip and the metacarpophalangeal joint of each digit. Hand maps were
constructed using a 3D motion capture system. Participants in the Haptics-only
group produced the most accurate hand maps. We discuss the possibility that
vision interferes with somatosensory processing.
PMID- 28502023
TI - Sources of Care for Alcohol and Other Drug Problems: The Role of the African
American Church.
AB - African Americans experience significant disparities in treatment access,
retention, and quality of care for alcohol and drug use (AOD) problems. Religious
congregations, often the first point of contact for help with AOD problems, can
play an integral role in improving access to treatment. However, little is known
about the role of African American churches in addressing AOD problems. We
administered a survey to a faith-based collaborative of 169 African American
churches in Los Angeles to examine how AOD problems are identified in
congregations, the types of support provided, barriers to providing treatment
referrals, and factors associated with the provision of treatment referrals.
Seventy-one percent of churches reported caring often for individuals with AOD
problems. AOD problems came to the attention of congregations most commonly via a
concerned family member (55%) and less frequently through individuals with AOD
problems directly approaching clergy (30%). In addition to providing spiritual
support, a substantial proportion of churches reported linking individuals to AOD
services through referrals (62%) and consultation with providers (48%). Barriers
to providing treatment referrals included lack of affordable programs (50%),
stigma (50%), lack of effective treatments (45%), and insufficient resources or
staff (45%). The likelihood of providing treatment referrals was greater among
mid-sized versus smaller-size congregations (OR 3.43; p < .05) and among
congregations with clergy that had attended seminary (OR 3.93; p < .05). Knowing
how to effectively coordinate informal sources of care provided by African
American churches with the formal service sector could make a significant impact
on AOD treatment disparities.
PMID- 28502024
TI - The Relationship Between Religious Beliefs and Quality of Life Among Patients
With Multiple Sclerosis.
AB - Patients with chronic diseases, such as multiple sclerosis (MS), are prone to
emotional distresses and reduction in life quality more than others. This study
aimed to assess the relationship between religious beliefs and quality of life
among patients with MS. In this study, 145 MS patients completed 36-Item Short
Form Health Survey (SF-36) and the Duke University Religion Index (DUREL)
questionnaires. The results indicated that unorganized religious activities were
significantly associated with marital status and education level. Besides,
internal religion was positively correlated to mental health. However, religious
variables were not effective prognostic factors in physical and mental quality of
life. Overall, further studies have to be conducted to determine the role of
religion in quality of life of MS patients with different religious backgrounds.
PMID- 28502025
TI - Mindfulness in Salah Prayer and its Association with Mental Health.
AB - Plethora of researches has been carried out for the last many decades and has
identified relationship between mental health and religious convictions; in
particular, range of religious practices has been found instrumental in the
promotion of mental health. The aim of this paper is to find out association
between mindfulness in Salah (prayer) and mental health of individuals who
identify themselves with Islam and to examine the mental health of those Muslims
who offer Salah prayer with mindfulness and those who offer without mindfulness.
A total of 174 participants with mean age of 21.57 including 62% males and
females 38% were selected through convenient sampling. RAND Mental Health
Inventory was used to measure mental health and other three variables; three self
reported measures were constructed. They included Islamic religious education
scale, Salah education scale and mindfulness in Salah scale. Psychometric
properties for all scales were established. The findings indicated that mean on
mindfulness and mental health was significantly higher for those who were
offering Salah (prayer) regularly (p < 0.01) as compared with those who were not
offering it regularly. Moreover, those who were offering Salah (prayer) with
mindfulness had also significantly higher mean for mental health (p < 0.01) as
compared with those who were offering it without mindfulness. Religious
education, Salah education and mindfulness were able to account for 13% of the
variance in mental health (p < 0.01). Of note two of the measures included Salah
education and mindfulness made a significant contribution in the prediction of
mental health (p < 0.01). The present study indicated that individuals who offer
prayer regularly and with mindfulness have better mental health as compared with
those who don't offer it regularly and with mindfulness. The findings of this
study urge to spread awareness regarding offering prayer regularly with
mindfulness for the better outcome of mental health in people.
PMID- 28502027
TI - Assessing the Actual Clinical Effectiveness of Metabolic/Bariatric Surgery for
the Type 2 Diabetes Therapy.
PMID- 28502026
TI - Dentin remineralizing ability and enhanced antibacterial activity of strontium
and hydroxyl ion co-releasing radiopaque hydroxyapatite cement.
AB - Dental caries is an infection of the mineralized tooth structures that advances
when acid secreted by bacterial action on dietary carbohydrates diffuses and
dissolves the tooth mineral leading to demineralization. During treatment,
clinicians often remove only the superficial infected tooth structures and retain
a part of affected carious dentin to prevent excessive dentin loss and pulp
exposure. Calcium hydroxide is used to treat the affected dentin because it is
alkaline, induces pulp-dentin remineralization and decreases bacterial infection.
Presence of strontium ions has also been reported to exhibit anticariogenic
activity, and promote enamel and dentin remineralization. The objective of the
present study was to develop novel hydroxyapatite cement from tetracalcium
phosphate which gradually releases hydroxyl and strontium ions to exhibit
antibacterial activity. Its potential to remineralize the dentin sections
collected from extracted human molar tooth was studied in detail. The pH of all
the experimental cements exhibited a gradual increase to ~10.5 in 10 days with
10% strontium substituted tetracalcium phosphate cement (10SC) showing the
highest pH value which was sustained for 6 weeks. 10SC showed better
antibacterial property against S. aureus and E. coli at the end of 1 week
compared to other cements studied. It also exhibited the highest radiopacity
equivalent to 4.8 mm of Al standard. 10SC treated dentin section showed better
remineralization ability and highest elastic modulus. We can conclude that the
hydroxyl and strontium ions releasing tetracalcium phosphate cement exhibits good
antibacterial property, radiopacity and has the potential to encourage dentin
remineralization.
PMID- 28502028
TI - Hypoglycemia Following Bariatric Surgery: Our 31-Year Experience.
AB - PURPOSE: The purposes of this study are to identify the cumulative incidence of
post-bariatric surgery hypoglycemia (PBSH), describe its symptomatology, and
characterize treatment patterns at a large academic institution. MATERIALS AND
METHODS: All patients who underwent bariatric surgery at a single institution
from 1985 to 2015 were identified using a clinical database, administrative
billing data identified patients who were treated for hypoglycemia, and chart
reviews were performed to make a diagnosis of PBSH based on Whipple's triad. PBSH
cases were reviewed including patient diabetes history, symptomatology, and
treatment measures. Univariate analyses were performed to identify correlations
based on symptomatology, laboratory values, and treatments utilized. RESULTS:
Ninety (2.6%) of 3487 patients were diagnosed with PBSH with preoperative median
age of 43 years, mean BMI of 50.0 kg/m2, and median glycated hemoglobin of 6.0%.
Median time-to-first hypoglycemic event was 40.6 months. No factors were
identified which predict symptom severity or resolution. The 24 (27%) patients
who received pharmacotherapy to treat hypoglycemia were younger, had lower nadir
blood glucose levels, and more frequent symptoms. Sixty-nine (79%) cases
eventually resolved. CONCLUSIONS: PBSH onset and severity are highly variable.
Successful management of these patients can prove difficult and should include
dietary therapy, the selective use of pharmacotherapy and surgery, and the use of
a multidisciplinary team including bariatric surgeons and endocrinologists.
PMID- 28502029
TI - A Longitudinal Analysis of Short-Term Costs and Outcomes in a Regionalized Center
of Excellence Bariatric Care System.
AB - BACKGROUND: Evaluating how morbidity and costs evolve for new bariatric centers
is vital to understanding the expected length of time required to reach optimal
outcomes and cost efficiencies. Accordingly, the objective of this study was to
evaluate how morbidity and costs changed longitudinally during the first 5 years
of a regionalized center of excellence system. METHODS: This was a longitudinal
analysis of the first 5 years of a bariatric center of excellence system. The
main outcomes of interest were all-cause morbidity and cost for the index
admission. Predictors of interest included patient demographics, comorbidities,
annual hospital and surgeon volume, fellowship teaching center status, and year
of procedure. Hierarchical regression models were used to determine predictors of
morbidity and costs. RESULTS: Procedures done in 2012 (OR 0.65, 95%CI 0.52-0.79;
p < 0.001), 2013 (OR 0.63, 95%CI 0.51-0.78; p < 0.001), and 2014 (OR 0.53, 95%CI
0.43-0.65; p < 0.001) all conferred a significantly lower odds of morbidity when
compared to the initial 2009/2010 years. Surgeon volume was associated with a
decreased odds of morbidity as for each increase in 25 bariatric cases per year
the odds of all-cause morbidity was 0.94 lower (95%CI 0.88-1.00; p = 0.04). There
was no significant variation at the hospital or surgeon level in perioperative
outcomes. CONCLUSION: This study determined that volume was important even for
high resource, fellowship-trained surgeons. It also found a decrease in morbidity
over time for new centers. Lastly, there was little variation in outcomes across
hospitals and surgeons suggesting that strict accreditation standards can help to
ensure high quality across hospital sites.
PMID- 28502030
TI - Co-occurrence of type I CALR and two MPL mutations in patient with primary
myelofibrosis.
PMID- 28502031
TI - Vitamin D and plasma cell dyscrasias: reviewing the significance.
AB - Monoclonal gammopathy of undetermined significance (MGUS) is a clonal plasma cell
disorder and precursor disease to multiple myeloma and other related cancers.
While MGUS is considered a benign disorder, with a low risk of disease
progression, patients have altered bone microarchitecture and an increased risk
of bone fracture. In addition, alterations in immune function are regularly found
to correlate with disease activity. Vitamin D, an important hormone for bone and
immune health, is commonly deficient in multiple myeloma patients. However,
vitamin D deficiency is also prevalent in the general population. The purpose of
this review is to highlight the current understanding of vitamin D in health and
disease and to parallel this with a review of the abnormalities found in plasma
cell dyscrasias. While some consensus statements have advocated for vitamin D
testing and routine supplementation in MGUS, there is no clear standard of care
approach and clinical practice patterns vary. Further research is needed to
better understand how vitamin D influences outcomes in MGUS patients.
PMID- 28502033
TI - A reflection on today's environment for child and adolescent psychiatric
research. The continuous march for science of European Child + Adolescent
Psychiatry.
PMID- 28502032
TI - Circulating markers of bone turnover.
AB - Renal osteodystrophy is a feature of chronic kidney disease (CKD), with
increasing prevalence as CKD progresses. This bone disease is responsible for
major morbidity, including fractures, and a deterioration in the quality of life
and its sequelae. Circulating biomarkers of renal osteodystrophy typically
indicate bone turnover, but not other features of bone, like bone volume,
mineralization, quality or strength. Bone turnover can be considered to be
primarily a reflection of bone cell activity, in particular that of osteoblasts
and osteoclasts. Since current treatments for bone disease usually target
cellular activity, biomarkers are considered to be able to contribute to the
decision-making for treatment and its follow-up. In CKD, one has to consider the
impact of a diminished clearance of biomarkers or their altered metabolism, both
potentially limiting its clinical use. Here, several aspects of the most
frequently used biomarkers of bone turnover are reviewed, with an emphasis on the
specific situation represented by CKD. This review is based on the overview
lecture at the symposium held in Amsterdam, September 23, 2016: "The Bone In
CKD", organized by the CKD-MBD working group of ERA-EDTA.
PMID- 28502035
TI - Prospective Observational Post-Marketing Study of Tafluprost for Glaucoma and
Ocular Hypertension: Effectiveness and Treatment Persistence.
AB - INTRODUCTION: The aim of this study was to investigate the long-term intraocular
pressure (IOP)-lowering effect and safety of tafluprost, a prostaglandin
analogue, in actual clinical practice and to determine persistency of tafluprost
as an indicator of its benefit-risk balance. METHODS: This was a large-scale,
post-marketing, multicenter, non-interventional, open-label, long-term study.
Patients with glaucoma or ocular hypertension who initiated tafluprost treatment
were registered and prospectively observed over a 2-year period in the real-world
setting in Japan. Long-term IOP and safety data were collected. RESULTS: Of the
4502 patients registered from 553 medical institutions, 4265 patients were
analyzed. The majority of patients had normal-tension glaucoma (44.4%) and
primary open-angle glaucoma (37.8%), and patients with ocular hypertension
constituted 7.0%. Treatment patterns with tafluprost during the study period were
as follows: naive monotherapy (48.1%), switching monotherapy (18.4%), and
concomitant therapy (33.5%). In all patients analyzed, mean IOP was significantly
reduced from 18.6 +/- 5.9 mmHg (month 0) to 15 mmHg or below throughout the 2
year observation period after initiation of tafluprost. Significant IOP-lowering
effects were shown in various treatment patterns and disease types. Adverse
reactions were observed in 795 patients (18.64%). Major adverse reactions
included eyelid pigmentation, ocular hyperemia, eyelash changes, eyelid
hypertrichosis, and iris hyperpigmentation. Kaplan-Meier curves showed that 84.6%
and 76.1% of patients were persistent on tafluprost for 1 and 2 years,
respectively, when discontinuation due to insufficient efficacy or adverse events
was defined as a treatment failure event. Furthermore, among treatment-naive
patients (n = 2304), the persistency rates on tafluprost monotherapy were 77.0%
for 1 year and 67.0% for 2 years. CONCLUSION: Tafluprost showed significant long
term IOP-lowering effects regardless of treatment patterns or diagnosis, with
minimum safety concerns in the actual clinical practice. The observed treatment
persistence suggests that tafluprost can be used long term owing to its benefit
risk profile. FUNDING: Santen Pharmaceutical Co., Ltd., Osaka, Japan.
PMID- 28502034
TI - Stressful life events during adolescence and risk for externalizing and
internalizing psychopathology: a meta-analysis.
AB - The main objective of the present research was to analyze the relations between
stressful life events and the externalizing and internalizing spectra of
psychopathology using meta-analytical procedures. After removing the duplicates,
a total of 373 papers were found in a literature search using several
bibliographic databases, such as the PsycINFO, Medline, Scopus, and Web of
Science. Twenty-seven studies were selected for the meta-analytical analysis
after applying different inclusion and exclusion criteria in different phases.
The statistical procedure was performed using a random/mixed-effects model based
on the correlations found in the studies. Significant positive correlations were
found in cross-sectional and longitudinal studies. A transactional effect was
then found in the present study. Stressful life events could be a cause, but also
a consequence, of psychopathological spectra. The level of controllability of the
life events did not affect the results. Special attention should be given to the
usage of stressful life events in gene-environment interaction and correlation
studies, and also for clinical purposes.
PMID- 28502038
TI - Verbal, Visual, and Intermediary Support for Child Witnesses with Autism During
Investigative Interviews.
AB - Three promising investigative interview interventions were assessed in 270
children (age 6-11 years): 71 with autism spectrum disorder (ASD) and 199 who
were typically developing (TD). Children received 'Verbal Labels', 'Sketch
Reinstatement of Context' or 'Registered Intermediary' interviews designed to
improve interview performance without decreasing accuracy. Children with ASD
showed no increases in the number of correct details recalled for any of the
three interview types (compared to a Best-Practice police interview), whereas TD
children showed significant improvements in the Registered Intermediary and
Verbal Labels interviews. Findings suggested that children with ASD can perform
as well as TD children in certain types of investigative interviews, but some
expected benefits (e.g., of Registered Intermediaries) were not apparent in this
study.
PMID- 28502036
TI - Perceptions of Painful Diabetic Peripheral Neuropathy in South-East Asia: Results
from Patient and Physician Surveys.
AB - : There are no data on physician-patient communication in painful diabetic
peripheral neuropathy (pDPN) in the Asia-Pacific region. The objective of this
study was to examine patient and physician perceptions of pDPN and clinical
practice behaviors in five countries in South-East Asia. Primary care physicians
and practitioners, endocrinologists, diabetologists, and patients with pDPN
completed separate surveys on pDPN diagnosis, impact, management, and physician
patient interactions in Hong Kong, Malaysia, the Philippines, Taiwan, and
Thailand. Data were obtained from 100 physicians and 100 patients in each
country. The majority of physicians (range across countries, 30-85%) were primary
care physicians and practitioners. Patients were mostly aged 18-55 years and had
been diagnosed with diabetes for >5 years. Physicians believed pDPN had a greater
impact on quality of life than did patients (ranges 83-92% and 39-72%,
respectively), but patients believed pDPN had a greater impact on items such as
sleep, anxiety, depression, and work than physicians. Physicians considered the
diagnosis and treatment of pDPN a low priority, which may be reflected in the
generally low incidence of screening (range 12-65%) and a lack of awareness of
pDPN. Barriers to treatment included patients' lack of awareness of pDPN. Both
physicians and patients agreed that pain scales and local language descriptions
were the most useful tools in helping to describe patients' pain. Most patients
were monitored upon diagnosis of pDPN (range 55-97%), but patients reported a
shorter duration of monitoring compared with physicians. Both physicians and
patients agreed that it was patients who initiated conversations on pDPN.
Physicians most commonly referred to guidelines from the American Diabetes
Association or local guidelines for the management of pDPN. This study highlights
important differences between physician and patient perceptions of pDPN, which
may impact on its diagnosis and treatment. For a chronic and debilitating
complication like pDPN, the physician-patient dialogue is central to maximizing
patient outcomes. Strategies, including education of both groups, need to be
developed to improve communication. FUNDING: Pfizer.
PMID- 28502039
TI - Possible involvement of the lipoxygenase and leukotriene signaling pathways in
cisplatin-mediated renal toxicity.
AB - PURPOSE: The present study examined the possible involvement of the lipoxygenase
(LOX) pathway in cisplatin (CPT)-induced nephrotoxicity. METHODS: Wistar albino
rats were challenged with CPT IP injection (7.5 mg/kg) and were sacrificed after
one week. Signs of renal dysfunction, including urea and creatinine clearance
levels and renal histological structure, were investigated. Gene and protein
expression levels of different LOX pathway enzymes and products, including 5-LOX,
12-LOX, 15-LOX, 5-LOX activating protein (FLAP), leukotriene A4 hydrolase (LTA4
hydrolase), leukotriene C4 synthase (LTC4 synthase), LTB4 receptor, and cysteinyl
(cys) LT receptor types 1 and 2, were also determined in the kidneys using real
time PCR and western blotting, respectively. The serum and kidney levels of LTB4
and inflammatory markers were also estimated. RESULTS: CPT renal toxicity was
established as the creatinine and urea clearance levels were significantly
reduced, while the serum levels of creatinine and urea were markedly increased.
We reported a considerable up-regulation in the mRNA and protein expression
levels of 5-LOX, FLAP, 12-LOX, LTA4 hydrolase, LTC4 synthase, LTB4 receptor, and
Cys LT receptor types 1 and 2, while 15-LOX expression did not significantly
change in the CPT group. Additionally, LTB4 and inflammatory indicators in serum
and renal levels were elevated significantly in the CPT group. Histopathological
examination clearly showed the nephrotoxic changes in the renal tissues of CPT
challenged animals. CONCLUSIONS: Our findings suggested, for the first time, the
participation of LOX enzymes and products in the signaling pathway leading to CPT
associated nephrotoxicity, which could be the foundation stone for combining LOX
pathway attenuators with CPT therapy to decrease CPT-associated renal toxicity.
PMID- 28502037
TI - The Role of the Broader Autism Phenotype and Environmental Stressors in the
Adjustment of Siblings of Children with Autism Spectrum Disorders in Taiwan and
the United Kingdom.
AB - The influence of the broader autism phenotype (BAP) on the adjustment of siblings
of children with autism has previously been researched mainly in Western
cultures. The present research evaluated a diathesis-stress model of sibling
adjustment using a questionnaire study including 80 and 75 mother-typically
developing sibling dyads in Taiwan and the United Kingdom (UK). UK siblings
reported elevated adjustment difficulties compared to the Taiwanese sample and to
normative data. Whilst higher BAP levels were generally associated with greater
adjustment difficulties, differences were found across cultures and respondents.
Although significant diathesis-stress interactions were found, these were in the
opposite direction from those predicted by the model, and differed across
cultural settings. Implications for culturally-sensitive sibling support are
considered.
PMID- 28502040
TI - UGT1A1 polymorphisms with irinotecan-induced toxicities and treatment outcome in
Asians with Lung Cancer: a meta-analysis.
AB - Previous studies of irinotecan pharmacogenetics have shown that the UGT1A1*28
polymorphism has an effect on irinotecan (IRI)-induced toxicities in Caucasians.
Yet compared with the UGT1A1*6 mutation, the UGT1A1*28 occurs at a much lower
frequency in the Asians. Whether UGT1A1*6 and UGT1A1*28 are associated with IRI
induced neutropenia, diarrhea and IRI-based chemotherapy tumor response (TR) in
Asians with lung cancer remains controversial. In this meta-analysis, we found a
higher risk of neutropenia and diarrhea with IRI-based chemotherapy in Asians
with lung cancer carrying the UGT1A1*6 polymorphism. However, UGT1A1*28 showed a
weak correlation with diarrhea, but no significant correlation with neutropenia.
Neither UGT1A1*6 nor UGT1A1*28 is associated with IRI-based chemotherapy TR.
These data suggest that the UGT1A1*28 polymorphism may not be a suitable
biomarker to predict IRI-induced toxicities and chemotherapy TR in Asians, while
UGT1A*6 polymorphism is associated with a higher risk of IRI-induced neutropenia
and diarrhea, but not IRI-based chemotherapy TR.
PMID- 28502041
TI - Glucose Can Epigenetically Alter the Gene Expression of Neurotrophic Factors in
the Murine Brain Cells.
AB - Glucose is believed to improve the memory in both human and mice, but the
detailed insights were mostly elusive. In this study, we focused on two major
neurotrophic factors, brain-derived neurotrophic factor (BDNF) and fibroblast
growth factor 1 (FGF1), which are believed to be associated with the memory
enhancement and assessed their expressional regulation among the murine neuronal
and glial cells. Our findings showed that the glucose administration increased
phosphorylated Akt, phosphorylated CREB, exon 1- and exon 4-specific BDNF
transcripts, and FGF1 transcripts that are associated with the epigenetic changes
expected to open the chromatin and a reduction in histone deacetylase 2 (HDAC2)
in neurons and astrocytes of the murine hippocampus. The glucose administration
enhanced the long-term potentiation and the number of dendritic spines in the CA1
and CA3 subfields of hippocampus. The intrahippocampal injection of short hairpin
RNA against TrkB canceled the glucose-mediated memory enhancement. Like the
glucose, we also report that the HDAC inhibitor can enhance the memory through
the BDNF-TrkB pathway but it targeted different brain cell populations to enhance
the BDNF and FGF1 transcripts. In addition, the soluble FGF1 treatments
significantly increased the BDNF expression in astrocytes and neurons, suggesting
that the glucose-mediated induction of the neurotrophic factors could contribute
to the memory. Our study provides the valuable insights, explaining the
distinctive neuronal and glial cell regulation of the neurotrophic factors by
glucose and HDAC inhibitor, which could likely explain how our brain cells can
control the release of neurotrophic factors.
PMID- 28502042
TI - Tale of the Good and the Bad Cdk5: Remodeling of the Actin Cytoskeleton in the
Brain.
AB - Cdk5 kinase, a cyclin-dependent kinase family member, is a key regulator of
cytoskeletal remodeling in the brain. Cdk5 is essential for brain development
during embryogenesis. After birth, it is essential for numerous neuronal
processes such as learning and memory formation, drug addiction, pain signaling,
and long-term behavior changes, all of which rely on rapid alterations in the
cytoskeleton. Cdk5 activity is deregulated in various brain disorders including
Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and
ischemic stroke, resulting in profound remodeling of the neuronal cytoskeleton,
loss of synapses, and ultimately neurodegeneration. This review focuses on the
"good and bad" Cdk5 in the brain and its pleiotropic contribution in regulating
neuronal actin cytoskeletal remodeling. A vast majority of physiological and
pathological Cdk5 substrates are associated with the actin cytoskeleton. Thus,
our special emphasis is on the numerous Cdk5 substrates identified in the past
two decades such as ephexin1, p27, Mst3, CaMKv, kalirin-7, RasGRF2, Pak1, WAVE1,
neurabin-1, TrkB, 5-HT6R, talin, drebrin, synapsin I, synapsin III, CRMP1, GKAP,
SPAR, PSD-95, and LRRK2. These substrates have unraveled the molecular mechanisms
by which Cdk5 plays divergent roles in regulating neuronal actin cytoskeletal
dynamics both in healthy and diseased states.
PMID- 28502043
TI - Different Hippocampus Functional Connectivity Patterns in Healthy Young Adults
with Mutations of APP/Presenilin-1/2 and APOEepsilon4.
AB - This study aims to explore the hippocampus-based functional connectivity patterns
in young, healthy APP and/or presenilin-1/2 mutation carriers and APOE epsilon4
subjects. Seventy-eight healthy young adults (33 male, mean age 24.0 +/- 2.2
years; 18 APP and/or presenilin1/2 mutation carriers [APP/presenilin-1/2 group],
30 APOE epsilon4 subjects [APOE epsilon4 group], and 30 subjects without the
above-mentioned genes [control group]) underwent resting-state functional MR
imaging and neuropsychological assessments. Bilateral hippocampus functional
connectivity patterns were compared among three groups. The brain regions with
statistical differences were then extracted, and correlation analyses were
performed between Z values of the brain regions and neuropsychological results.
Compared with control group, both APOE epsilon4 group and APP/presenilin-1/2
group showed increased functional connectivity in medial prefrontal cortex and
precuneus for the seeds of bilateral hippocampi. The APOE epsilon4 group
displayed increased functional connectivity from bilateral hippocampi to the left
middle temporal gyrus compared with the control group. Moreover, compared with
the APP/presenilin-1/2 group, the APOE epsilon4 group also had markedly increased
functional connectivity in right hippocampus-left middle temporal gyrus. The Z
values of right hippocampus-left middle temporal gyrus correlated with various
neuropsychological results across all the subjects, as well as in APOE epsilon4
group. Young healthy adults carrying APOE epsilon4 and APP/presenilin-1/2
displayed different hippocampus functional connectivity patterns, which may
underlie the discrepant mechanisms of gene-modulated cognitive dysfunction in
Alzheimer's disease.
PMID- 28502046
TI - Adapting the Vegetative Vigour Terrestrial Plant Test for assessing ecotoxicity
of aerosol samples.
AB - Plants, being recognized to show high sensitivity to air pollution, have been
long used to assess the ecological effects of airborne contaminants. However,
many changes in vegetation are now generally attributed to atmospheric deposition
of aerosol particles; the dose-effect relationships of this process are usually
poorly known. In contrast to bioindication studies, ecotoxicological tests (or
bioassays) are controlled and reproducible where ecological responses are
determined quantitatively. In our study, the No. 227 OECD Guideline for the
Testing of Chemicals: Terrestrial Plant Test: Vegetative Vigour Test (hereinafter
referred to as 'Guideline') was adapted and its applicability for assessing the
ecotoxicity of water-soluble aerosol compounds of aerosol samples was evaluated.
In the aqueous extract of the sample, concentration of metals, benzenes,
aliphatic hydrocarbons and PAHs was determined analytically. Cucumis sativus L.
plants were sprayed with the aqueous extract of urban aerosol samples collected
in a winter sampling campaign in Budapest. After the termination of the test, on
day 22, the following endpoints were measured: fresh weight, shoot length and
visible symptoms. The higher concentrations applied caused leaf necrosis due to
toxic compounds found in the extract. On the other hand, the extract elucidated
stimulatory effect at low concentration on both fresh weight and shoot length.
The test protocol, based on the Guideline, seems sensitive enough to assess the
phytotoxicity of aqueous extract of aerosol and to establish clear cause-effect
relationship.
PMID- 28502047
TI - Evaluation of various solvent systems for lipid extraction from wet microalgal
biomass and its effects on primary metabolites of lipid-extracted biomass.
AB - Microalgae have tremendous potential to grow rapidly, synthesize, and accumulate
lipids, proteins, and carbohydrates. The effects of solvent extraction of lipids
on other metabolites such as proteins and carbohydrates in lipid-extracted algal
(LEA) biomass are crucial aspects of algal biorefinery approach. An effective and
economically feasible algae-based oil industry will depend on the selection of
suitable solvent/s for lipid extraction, which has minimal effect on metabolites
in lipid-extracted algae. In current study, six solvent systems were employed to
extract lipids from dry and wet biomass of Scenedesmus obliquus. To explore the
biorefinery concept, dichloromethane/methanol (2:1 v/v) was a suitable solvent
for dry biomass; it gave 18.75% lipids (dry cell weight) in whole algal biomass,
32.79% proteins, and 24.73% carbohydrates in LEA biomass. In the case of wet
biomass, in order to exploit all three metabolites, isopropanol/hexane (2:1 v/v)
is an appropriate solvent system which gave 7.8% lipids (dry cell weight) in
whole algal biomass, 20.97% proteins, and 22.87% carbohydrates in LEA biomass.
Graphical abstract: Lipid extraction from wet microalgal biomass and biorefianry
approach.
PMID- 28502044
TI - Hippocampal Proteomic Analysis Reveals Distinct Pathway Deregulation Profiles at
Early and Late Stages in a Rat Model of Alzheimer's-Like Amyloid Pathology.
AB - The cerebral accumulation and cytotoxicity of amyloid beta (Abeta) is central to
Alzheimer's pathogenesis. However, little is known about how the amyloid
pathology affects the global expression of brain proteins at different disease
stages. In order to identify genotype and time-dependent significant changes in
protein expression, we employed quantitative proteomics analysis of hippocampal
tissue from the McGill-R-Thy1-APP rat model of Alzheimer-like amyloid pathology.
McGill transgenic rats were compared to wild-type rats at early and late
pathology stages, i.e., when intraneuronal Abeta amyloid burden is conspicuous
and when extracellular amyloid plaques are abundant with more pronounced
cognitive deficits. After correction for multiple testing, the expression levels
of 64 proteins were found to be considerably different in transgenic versus wild
type rats at the pre-plaque stage (3 months), and 86 proteins in the post-plaque
group (12 months), with only 9 differentially regulated proteins common to the 2
time-points. This minimal overlap supports the hypothesis that different
molecular pathways are affected in the hippocampus at early and late stages of
the amyloid pathology throughout its continuum. At early stages, disturbances in
pathways related to cellular responses to stress, protein homeostasis, and
neuronal structure are predominant, while disturbances in metabolic energy
generation dominate at later stages. These results shed new light on the
molecular pathways affected by the early accumulation of Abeta and how the
evolving amyloid pathology impacts other complex metabolic pathways.
PMID- 28502048
TI - The effects of cadmium pulse dosing on physiological traits and growth of the
submerged macrophyte Vallisneria spinulosa and phytoplankton biomass: a mesocosm
study.
AB - Pulse inputs of heavy metals are expected to increase with a higher frequency of
extreme climate events (heavy rain), leading to stronger erosion of contaminated
and fertilized farmland soils to freshwaters, with potentially adverse effects on
lake ecosystems. We conducted a 5-month mesocosm study to elucidate the responses
of the submerged macrophyte Vallisneria spinulosa and phytoplankton to four
different doses of cadmium (Cd): 0 (control), 0.05, 0.5, and 5 g m-2 (CK, I, II,
and III, respectively) under mesotrophic conditions. We found that total
phosphorus concentrations were larger in the three Cd pulse treatments, whereas
total nitrogen concentrations did not differ among the four treatments. The
contents of chlorophyll a and soluble sugar in macrophyte leaves decreased in
III, and total biomass, ramet number, plant height, and total stolon length of
macrophytes were lower in both II and III. In contrast, abundances of the three
main phytoplankton taxa-Cyanophyta, Chlorophyta, and Bacillariophyta-did not
differ among treatments. Total phytoplankton biomass was, however, marginally
lower in CK than in the Cd treatments. We conclude that exposure to strong Cd
pulses led to significantly reduced growth of macrophytes, while no obvious
effect appeared for phytoplankton.
PMID- 28502045
TI - A Clinical and Molecular Genetic Study of 50 Families with Autosomal Recessive
Parkinsonism Revealed Known and Novel Gene Mutations.
AB - In this study, the role of known Parkinson's disease (PD) genes was examined in
families with autosomal recessive (AR) parkinsonism to assist with the
differential diagnosis of PD. Some families without mutations in known genes were
also subject to whole genome sequencing with the objective to identify novel
parkinsonism-related genes. Families were selected from 4000 clinical files of
patients with PD or parkinsonism. AR inheritance pattern, consanguinity, and a
minimum of two affected individuals per family were used as inclusion criteria.
For disease gene/mutation identification, multiplex ligation-dependent probe
amplification, quantitative PCR, linkage, and Sanger and whole genome sequencing
assays were carried out. A total of 116 patients (50 families) were examined.
Fifty-four patients (46.55%; 22 families) were found to carry pathogenic
mutations in known genes while a novel gene, not previously associated with
parkinsonism, was found mutated in a single family (2 patients). Pathogenic
mutations, including missense, nonsense, frameshift, and exon rearrangements,
were found in Parkin, PINK1, DJ-1, SYNJ1, and VAC14 genes. In conclusion,
variable phenotypic expressivity was seen across all families.
PMID- 28502049
TI - Evaluation of carbofuran-mediated toxicity against human lymphocytes and red
blood cells in simulated wastewater degraded by coagulation-flocculation.
AB - Coagulation-flocculation in water treatment has been relied upon aluminum (Al)
and iron (Fe) salts for treatment of contaminants present in source waters
containing dissolved organic compounds. However, water quality deteriorates day
by day which makes it urgent to improve the standards of the treatment procedure.
Coagulation-flocculation-sedimentation performance of ferric chloride and alum
was comparatively investigated for carbofuran treatment in simulated wastewater.
Coagulation trails were performed in a jar test at several pH levels and
coagulant doses to determine reduction efficiencies of carbofuran degradation and
chemical oxygen demand (COD). Effect of carbofuran on proliferation, viability,
and direct cytotoxicity was performed using human neuroblastoma cells U-87.
Direct toxicity of carbofuran on human mononuclear cells and red blood cells
(RBC) was also analyzed. Carbofuran and its derivatives were found to be
relatively safe at low concentration (2-5 MUM). However, at slightly higher
concentration (8 MUM), a moderate loss in viability and proliferative potential
was observed. Taken together, these results suggest that carbofuran appears to be
safe at moderate or low concentration with respect to viability of normal human
lymphocytes and RBC.
PMID- 28502050
TI - Biogeochemical controls on mercury methylation in the Allequash Creek wetland.
AB - We measured mercury methylation potentials and a suite of related biogeochemical
parameters in sediment cores and porewater from two geochemically distinct sites
in the Allequash Creek wetland, northern Wisconsin, USA. We found a high degree
of spatial variability in the methylation rate potentials but no significant
differences between the two sites. We identified the primary geochemical factors
controlling net methylmercury production at this site to be acid-volatile
sulfide, dissolved organic carbon, total dissolved iron, and porewater iron(II).
Season and demethylation rates also appear to regulate net methylmercury
production. Our equilibrium speciation modeling demonstrated that sulfide likely
regulated methylation rates by controlling the speciation of inorganic mercury
and therefore its bioavailability to methylating bacteria. We found that no
individual geochemical parameter could explain a significant amount of the
observed variability in mercury methylation rates, but we found significant
multivariate relationships, supporting the widely held understanding that net
methylmercury production is balance of several simultaneously occurring
processes.
PMID- 28502051
TI - Cadmium impact, accumulation and detection in poplar callus cells.
AB - Effect of cadmium cations and their interaction with silicon cations was
determined in poplar calli and expressed as changes in callus growth, cell
viability and cadmium cation accumulation. Cell viability throughout culture
versus cadmium cation accumulation in cells is discussed. At the same time, the
study sought appropriate methods for cadmium cation detection in callus cells and
also in experiments with low plant material (e.g. protoplasts). Cadmium cations
were determined by atomic absorption spectroscopy and using fluorescence
microscopy with a specific cadmium cation fluorescent dye. The detection of
cadmium cations in callus cells by the latter method appears suitable because the
callus cells are surrounded by primary cell walls without auto-fluorescence and
these values fit well with atomic absorption spectroscopy quantification.
However, the visualisation method has some limits discussed below.
PMID- 28502052
TI - Variation of microbial communities and functional genes during the biofilm
formation in raw water distribution systems and associated effects on the
transformation of nitrogen pollutants.
AB - This study aimed to investigate the variation of microbial communities and
functional genes during the biofilm formation in raw water distribution systems
without prechlorination and associated effects on the transformation of nitrogen
pollutants by using a designed model pipe system. The results showed the
transformation of nitrogen pollutants was obvious during the biofilm formation.
The richness and diversity of the microbial communities changed significantly.
The higher abundance of Nitrospirae in biofilm samples significantly contributed
to biological nitrification. In particular, the stable content of Bacteroidetes
in the biofilm and soluble microbial products released by the biomass might have
enhanced the increase in dissolved organic nitrogen. In addition, the variation
tendency of nitrogen functional gene abundances and their strong effects on NH4+
N, NO2--N, and NO3--N transformation were clearly observed. These findings
provide new insights into the evolution of microbial communities and functional
genes during the initial operation period of real-world raw water distribution
pipes and highlight management and possible safety issues in the subsequent water
treatment process.
PMID- 28502053
TI - Synthesis of a ternary Ag/RGO/ZnO nanocomposite via microwave irradiation and its
application for the degradation of Rhodamine B under visible light.
AB - Reduced graphene oxide supporting plasmonic photocatalyst (Ag) on ZnO has been
synthesized via a facile two-step microwave synthesis using RGO/ZnO and AgNO3.
First step involves fabrication of RGO/ZnO via microwave irradiation. The
nanocomposites were characterized by X-ray diffraction analysis, transmission
electron microscopy, Fourier transform infrared spectroscopy, and Raman
spectroscopy. Ag/RGO/ZnO shows enhanced photoactivity under visible light for the
degradation of Rhodamine B. Enhanced charge separation and migration have been
assigned using UV-vis diffuse reflectance spectra, photoluminescence spectra,
electrochemical impedance spectra, and TCSPC analysis. The improved photoactivity
of Ag/RGO/ZnO can be ascribed to the prolonged lifetime of photogenerated
electron-hole pairs and effective interfacial hybridization between RGO and Ag
with ZnO nanoparticles. Ag nanoparticles can absorb visible light via surface
plasmon resonance to enhance photocatalytic activity.
PMID- 28502054
TI - Light absorption of biomass burning and vehicle emission-sourced carbonaceous
aerosols of the Tibetan Plateau.
AB - Carbonaceous aerosols over the Tibetan Plateau originate primarily from biomass
burning and vehicle emissions (BB and VEs, respectively). The light absorption
characteristics of these carbonaceous aerosols are closely correlated with the
burning conditions and represent key factors that influence climate forcing. In
this study, the light absorption characteristics of elemental carbon (EC) and
water-soluble organic carbon (WSOC) in PM2.5 (fine particulate matter smaller
than 2.5 MUm) generated from BB and VEs were investigated over the Tibetan
Plateau (TP). The results showed that the organic carbon (OC)/EC ratios from BB-
and VE-sourced PM2.5 were 17.62 +/- 10.19 and 1.19 +/- 0.36, respectively. These
values were higher than the ratios in other regions, which was primarily because
of the diminished amount of oxygen over the TP. The mass absorption cross section
of EC (MACEC) at 632 nm for the BB-sourced PM2.5 (6.10 +/- 1.21 m2.g-1) was lower
than that of the VE-sourced PM2.5 (8.10 +/- 0.98 m2.g-1), indicating that the EC
content of the BB-sourced PM2.5 was overestimated because of the high OC/EC
ratio. The respective absorption per mass (alpha/rho) values at 365 nm for the VE
and BB-sourced PM2.5 were 0.71 +/- 0.17 m2.g-1 and 0.91 +/- 0.18 m2.g-1. The
alpha/rho value of the VEs was loaded between that of gasoline and diesel
emissions, indicating that the VE-sourced PM2.5 originated from both types of
emissions. Because OC and WSOC accounts for most of the carbonaceous aerosols at
remote area of the TP, the radiative forcing contributed by the WSOC should be
high, and requires further investigation.
PMID- 28502055
TI - Cardiovascular Risk Stratification in Patients with Metabolic Syndrome Without
Diabetes or Cardiovascular Disease: Usefulness of Metabolic Syndrome Severity
Score.
AB - INTRODUCTION: The estimated cardiovascular risk determined by the different risk
scores, could be heterogeneous in patients with metabolic syndrome without
diabetes or vascular disease. This risk stratification could be improved by
detecting subclinical carotid atheromatosis. AIMS: To estimate the cardiovascular
risk measured by different scores in patients with metabolic syndrome and analyze
its association with the presence of carotid plaque. METHODS: Non-diabetic
patients with metabolic syndrome (Adult Treatment Panel III definition) without
cardiovascular disease were enrolled. The Framingham score, the Reynolds score,
the new score proposed by the 2013 ACC/AHA Guidelines and the Metabolic Syndrome
Severity Calculator were calculated. Prevalence of carotid plaque was determined
by ultrasound examination. A Receiver Operating Characteristic analysis was
performed. RESULTS: A total of 238 patients were enrolled. Most patients were
stratified as "low risk" by Framingham score (64%) and Reynolds score (70.1%).
Using the 2013 ACC/AHA score, 45.3% of the population had a risk >=7.5%. A
significant correlation was found between classic scores but the agreement
(concordance) was moderate. The correlation between classical scores and the
Metabolic Syndrome Severity Calculator was poor. Overall, the prevalence of
carotid plaque was 28.2%. The continuous metabolic syndrome score used in our
study showed a good predictive power to detect carotid plaque (area under the
curve 0.752). CONCLUSION: In this population, the calculated cardiovascular risk
was heterogenic. The prevalence of carotid plaque was high. The Metabolic
Syndrome Severity Calculator showed a good predictive power to detect carotid
plaque.
PMID- 28502056
TI - Overexpression of the nitrate transporter, OsNRT2.3b, improves rice phosphorus
uptake and translocation.
AB - KEY MESSAGE: Overexpression of OsNRT2.3b in rice can increase Pi uptake and
accumulation through advanced root system, enhanced OsPT and OsPHR genes
expression, and the phloem pH homeostasis. Nitrogen (N) and phosphorus (P) are
two essential macronutrients for plants. Overexpression of the rice nitrate
transporter, OsNRT2.3b, can improve rice grain yield and nitrogen use efficiency
(NUE). Here, OsNRT2.3b overexpression resulted in increased grain yield, straw
yield, and grain:straw ratio, accompanied by increased P concentrations in the
leaf blade, leaf sheath, culm, and unfilled rice hulls. Overexpression of
OsNRT2.3b significantly increased 33Pi uptake compared with WT under 300-MUM Pi
but not 10-MUM Pi condition in 24 h. Moreover, the OsNRT2.3b-overexpressing rice
lines showed increased root and shoot biomass, root:shoot ratio, total root
length root surface area and N, P accumulation under 300- and 10-MUM Pi supply in
hydroponic solution. The levels of OsPT2, OsPT8, and OsPHR2 expression in roots
and of OsPT1 and OsPHR2 in shoots were upregulated in OsNRT2.3b-overexpressing
rice. These results indicated that OsNRT2.3b overexpression can improve rice P
uptake and accumulation, partially through the advanced root system, enhanced
gene expression, and the phloem pH regulation function.
PMID- 28502058
TI - Reversible cerebral vasoconstriction syndrome and antivitamin K anticoagulation:
challenges of an unusual association.
PMID- 28502057
TI - MicroRNA-125b in peripheral blood: a potential biomarker for severity and
prognosis of children with viral encephalitis.
AB - This study aims to evaluate the effect of peripheral blood miR-125b expression on
severity and prognosis in children with viral encephalitis (VE). Children with VE
(severe and mild groups) were grouped into VE group, and 40 healthy children as
control group. Plasma RNA was extracted, and real-time quantitative PCR was
conducted to detect miR-125b relative expression. Associations of miR-125b
expression with clinical characteristics and prognosis of VE children were
analyzed. Area under ROC curve (AUC) was calculated to evaluate the accuracy of
the prognostic value of miR-125b. Univariate analysis and logistic regression
analysis were performed to analyze risk factors of the prognoses of VE children.
The plasma miR-125b expression was higher in the VE group than in the control
group and higher in the severe group than the mild group. MiR-125b expression was
associated with status convulsion, hemiplegia, multiple organ injuries, and
stress hyperglycemia in VE children. Patients with poor prognosis exhibited
higher miR-125b expression than those with good prognosis, and the rate of high
miR-125b expression of the patients with poor prognosis (64.10%, 25/39) was
higher than that in those with good prognosis (28.92%, 24/83). The AUC of miR
125b expression to predict prognosis of VE children was 0.833. When the cutoff
value was 1.715, the diagnostic sensitivity (87.2%), specificity (71.1%), and
accuracy (76.2%) were the highest. Status convulsion, stress hyperglycemia, and
miR-125b were considered as risk factors for poor prognosis in VE children.
Peripheral blood miR-125b expression may be correlated with the severity and
prognosis of VE in children.
PMID- 28502059
TI - Dynamics of change in self-reported disability among persons with Parkinson's
disease after 2 years of follow-up.
AB - Symptoms of Parkinson's disease (PD) progress over time causing significant
disability. Yet, change in disability over shorter time periods has not been
entirely understood. The purpose of this study was to assess the Self-Assessment
Disability Scale (SADS) in persons with Parkinson's disease (PD) after 2 years of
follow-up and compare it with the score observed at baseline. Additionally, we
aimed at evaluating association of motor and non-motor PD features at baseline
with a higher disability after 2 years of follow-up. A total of 120 consecutive
persons with PD, who denied falling in the past 6 months, were initially
recruited. After 2 years of follow-up, 88 (73.3%) persons with PD were evaluated
for SADS. The total disability (SADS) score did not change after follow-up (p =
0.529). We observed increase in difficulty at "Getting out of bed" (p = 0.006),
"Getting up out of armchair" (p = 0.013), "Walking about house/flat" (p = 0.003),
"Walking outside" (p = 0.010), and "Traveling by public transport" (p = 0.014).
After adjusting for several potential confounding factors, falls in the past year
(beta = 8.32, 95% confidence interval (CI) 1.04-15.59) and higher Unified
Parkinson's Disease Rating Scale part 3 at baseline (beta = 0.26, 95%CI 0.01
0.51) remained associated with higher PD-related disability. This finding
suggests that accumulation of overall PD-related disability tends to occur over a
longer time span. Further studies are needed to gradually assess long-term
evolution of disability in PD.
PMID- 28502060
TI - Comparison of Univent tube and EZ blocker in one lung ventilation; airway
pressures and gas exchange.
AB - Univent tube (UT) and EZ-blocker were used for one-lung ventilation (OLV). UT is
a single lumen tube with a small separate lumen containing a bronchial blocker.
EZ-blocker differs with its unique y-shaped double-cuffed distal end. We aimed to
compare these two airway devices effects on airway pressures, oxygenation,
ventilation and haemodynamics during OLV. Patients undergoing elective
thoracotomy for the first time were included in this prospective randomized
study. Patients were divided into two groups as UT and EZ. Bronchial blockers
(BB) placement time was recorded. In lateral decubitus position, airway
pressures, static compliance, tidal volume (TV), respiratory rate (RR) and
haemodynamic findings were recorded before inflating the BB cuff (Pre-OLV) and
during OLV every 15 min. Arterial blood gas (ABG) samples were obtained before
and during OLV. 70 patients were enrolled in the study. The demographic
characteristics and data related to anesthesia and surgery were similar in both
groups. It took longer to place EZ than UT (p = 0.02). Ppeak values were similar
in both groups. Pplateau was significantly lower at the beginning of OLV (OLV15th
min) and higher at the end of OLV (pre-DLV) in EZ group compared to UT (p = 0.01,
p = 0.03). Cstatic were significantly higher at the beginning of OLV (OLV15th
min) in EZ group compared to UT (p = 0.01). During the following measurements,
Cstatic values were similar for both groups. Ventilation were achieved with
similar TV and RR. ABG findings and haemodynamic variables were similar. EZ and
Univent tube affected the airway pressures, oxygenation, ventilation and
haemodynamic variables similarly during OLV in patients with normal respiratory
function. These devices can be alternatives to each other based on clinical
conditions.
PMID- 28502061
TI - Validation of administrative case ascertainment algorithms for chronic childhood
arthritis in Manitoba, Canada.
AB - We validated case ascertainment algorithms for juvenile idiopathic arthritis
(JIA) in the provincial health administrative databases of Manitoba, Canada. A
population-based pediatric rheumatology clinical database from April 1st 1980 to
March 31st 2012 was used to test case definitions in individuals diagnosed at
<=15 years of age. The case definitions varied the number of diagnosis codes (1,
2, or 3), time frame (1, 2 or 3 years), time between diagnoses (ever, >1 day, or
>=8 weeks), and physician specialty. Positive predictive value (PPV),
sensitivity, and specificity with 95% confidence intervals (CIs) are reported. A
case definition of 1 hospitalization or >=2 diagnoses in 2 years by any provider
>=8 weeks apart using diagnosis codes for rheumatoid arthritis and ankylosing
spondylitis produced a sensitivity of 89.2% (95% CI 86.8, 91.6), specificity of
86.3% (95% CI 83.0, 89.6), and PPV of 90.6% (95% CI 88.3, 92.9) when seronegative
enthesopathy and arthropathy (SEA) was excluded as JIA; and sensitivity of 88.2%
(95% CI 85.7, 90.7), specificity of 90.4% (95% CI 87.5, 93.3), and PPV of 93.9%
(95% CI 92.0, 95.8) when SEA was included as JIA. This study validates case
ascertainment algorithms for JIA in Canadian administrative health data using
diagnosis codes for both rheumatoid arthritis (RA) and ankylosing spondylitis, to
better reflect current JIA classification than codes for RA alone. Researchers
will be able to use these results to define cohorts for population-based studies.
PMID- 28502062
TI - Significantly lengthened telomere in granulosa cells from women with polycystic
ovarian syndrome (PCOS).
AB - PURPOSE: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among
women at reproductive age. However, its etiology remains poorly understood.
Recent studies indicated that telomere length was related to PCOS. However, the
association between telomere length and PCOS has only been shown in leucocytes
and remained controversial across different studies. To clarify the association
between telomere length and PCOS, the current study interrogated telomere length
not only in leucocytes, but also in follicular granulosa cells, which is
essential for folliculogenesis and steroidogenesis. METHODS: Seventy-five
patients with PCOS and 81 controls with mechanical infertility undergoing their
first in vitro fertilization cycle were enrolled. Their peripheral blood and
granulosa cells were collected on the oocyte retrieval day. Telomere length of
both leucocytes in the blood and granulosa cells was assayed by quantitative
polymerase chain reaction. RESULTS: No significant difference was found in the
leucocyte telomere length between controls and PCOS patients (0.99 +/- 0.44 vs.
1.00 +/- 0.38, p = 0.93). Interestingly, when comparing telomere length in
granulosa cells between controls and PCOS subjects, significantly lengthened
telomere length was found in PCOS subjects (1.00 +/- 0.37 vs. 1.57+/-0.67, p <
0.0001). After adjustments for age and body mass index, the p value remained
significant (p < 0.0001). CONCLUSIONS: This finding reinforced the association
between telomere abnormalities and PCOS. Given the importance of telomere length
in cellular proliferation, our findings provided novel insights into the
pathophysiology of PCOS that abnormalities in telomere length possibly disturb
folliculogenesis and subsequently result in PCOS.
PMID- 28502064
TI - Optimization of Water/Oil/Surfactant System for Preparation of Medium-Chain
Length Poly-3-Hydroxyalkanoates (mcl-PHA)-Incorporated Nanoparticles via
Nanoemulsion Templating Technique.
AB - Polymeric nanoparticles gain a widespread interest in food and pharmaceutical
industries as delivery systems that encapsulate, protect, and release lipophilic
compounds such as omega-3 fatty acids, fat-soluble vitamins, carotenoids,
carvedilol, cyclosporine, and ketoprofen. In this study, medium-chain-length poly
3-hydroxyalkanoate (mcl-PHA)-incorporated nanoparticle was developed via facile
organic solvent-free nanoemulsion templating technique. The water content
(W/surfactant-to-oil (S/O)), S/O, and Cremophor EL-to-Span 80 (Cremo/Sp80) ratios
were first optimized using response surface methodology (RSM) to obtain
nanoemulsion template prior to incorporation of mcl-PHA. Their effects on
nanoemulsion formation were investigated. The mcl-PHA-incorporated nanoparticle
system showed a good preservation capability of beta-carotene and extended
storage stability.
PMID- 28502063
TI - Great ape gestures: intentional communication with a rich set of innate signals.
AB - Great apes give gestures deliberately and voluntarily, in order to influence
particular target audiences, whose direction of attention they take into account
when choosing which type of gesture to use. These facts make the study of ape
gesture directly relevant to understanding the evolutionary precursors of human
language; here we present an assessment of ape gesture from that perspective,
focusing on the work of the "St Andrews Group" of researchers. Intended meanings
of ape gestures are relatively few and simple. As with human words, ape gestures
often have several distinct meanings, which are effectively disambiguated by
behavioural context. Compared to the signalling of most other animals, great ape
gestural repertoires are large. Because of this, and the relatively small number
of intended meanings they achieve, ape gestures are redundant, with extensive
overlaps in meaning. The great majority of gestures are innate, in the sense that
the species' biological inheritance includes the potential to develop each
gestural form and use it for a specific range of purposes. Moreover, the
phylogenetic origin of many gestures is relatively old, since gestures are
extensively shared between different genera in the great ape family. Acquisition
of an adult repertoire is a process of first exploring the innate species
potential for many gestures and then gradual restriction to a final (active)
repertoire that is much smaller. No evidence of syntactic structure has yet been
detected.
PMID- 28502065
TI - Polymers for enhanced oil recovery: fundamentals and selection criteria.
AB - With a rising population, the demand for energy has increased over the years. As
per the projections, both fossil fuel and renewables will remain as major energy
source (678 quadrillion BTU) till 2030 with fossil fuel contributing 78% of total
energy consumption. Hence, attempts are continuously made to make fossil fuel
production more sustainable and cheaper. From the past 40 years, polymer flooding
has been carried out in marginal oil fields and have proved to be successful in
many cases. The common expectation from polymer flooding is to obtain 50%
ultimate recovery with 15 to 20% incremental recovery over secondary water
flooding. Both naturally derived polymers like xanthan gum and synthetic polymers
like partially hydrolyzed polyacrylamide (HPAM) have been used for this purpose.
Earlier laboratory and field trials revealed that salinity and temperature are
the major issues with the synthetic polymers that lead to polymer degradation and
adsorption on the rock surface. Microbial degradation and concentration are major
issues with naturally derived polymers leading to loss of viscosity and pore
throat plugging. Earlier studies also revealed that polymer flooding is
successful in the fields where oil viscosity is quite higher (up to 126 cp) than
injection water due to improvement in mobility ratio during polymer flooding. The
largest successful polymer flood was reported in China in 1990 where both
synthetic and naturally derived polymers were used in nearly 20 projects. The
implementation of these projects provides valuable suggestions for further
improving the available processes in future. This paper examines the selection
criteria of polymer, field characteristics that support polymer floods and
recommendation to design a large producing polymer flooding.
PMID- 28502067
TI - Predictive value of salivary microRNA-320a, vascular endothelial growth factor
receptor 2, CRP and IL-6 in Oral lichen planus progression.
AB - INTRODUCTION: MicroRNA (miRNA) 320a and vascular endothelial growth factor
receptor 2 (VEGFR-2) expression as the angiogenic biomarkers might be therapeutic
targets in Oral lichen planus (OLP). IL-6 and C-reactive protein (CRP) could be
prognostic in OLP, dysplastic OLP and Oral squamous cell carcinoma (OSCC).
Therefore, their salivary detections as the noninvasive tools were aimed in this
study. MATERIALS AND METHODS: Histopathologic examinations were carried out to
distinguish the patients with dysplastic OLP and OSCC. Salivary microRNA
expression analysis was performed using RT-qPCR. IL-6 and CRP levels were also
measured in saliva via ELISA method. VEGFR-2 expression in various sections was
evaluated using immunohistochemistry. RESULTS: A significant decrease in salivary
microRNA-320a in dysplastic OLP and OSCC but not in OLP without dysplasia was
found. VEGFR-2 visualization confirmed the increasing angiogenic process in these
cases. A significant increase in IL-6 level was detected in cases with OLP,
dysplastic OLP and OSCC. CRP levels also showed a significant increase in
dysplastic OLP and OSCC. A positive correlation between IL-6 and CRP levels was
found. CONCLUSION: Identification of the salivary microRNA-320a and hs-CRP might
provide a convenient noninvasive predictive tool for dysplastic OLP, whereas IL-6
could be a diagnostic and therapeutic target in both OLP without dysplasia and
dysplastic OLP cases.
PMID- 28502068
TI - Do Not Forget to Look at the Big Toe.
PMID- 28502066
TI - Ebselen ameliorates beta-amyloid pathology, tau pathology, and cognitive
impairment in triple-transgenic Alzheimer's disease mice.
AB - Alzheimer's disease (AD) is a progressive neurodegenerative disease which is
clinically characterized by memory loss and cognitive decline caused by protein
misfolding and aggregation. Imbalance between free radicals and the antioxidant
system is a prominent and early feature in the neuropathology of AD. Selenium
(Se), a vital trace element with excellent antioxidant potential, is
preferentially retained in the brain in Se-limited conditions and has been
reported to provide neuroprotection through resisting oxidative damage. In this
paper, we studied for the first time the potential of Ebselen, a lipid-soluble
selenium compound with GPx-like activity, in the treatment of cognitive
dysfunction and neuropathology of triple-transgenic AD (3 * Tg-AD) mice, AD model
cell, and primary culture. We demonstrated that Ebselen inhibited oxidative
stress in both AD model cells and mouse brains with increasing GPx and SOD
activities and meanwhile reduced p38 mitogen-activated protein kinases
activities. By decreasing the expression of amyloid precursor protein and beta
secretase, Ebselen reduced the levels of Abeta in AD neurons and mouse brains,
especially the most toxic oligomeric form. Besides, mislocation of phosphorylated
tau in neurons and phosphorylation levels of tau protein at Thr231, Ser396, and
Ser404 residues were also inhibited by Ebselen, probably by its regulatory roles
in glycogen synthase kinase 3beta and protein phosphatase 2A activity. In
addition, Ebselen mitigated the decrease of synaptic proteins including
synaptophysin and postsynaptic density protein 95 in AD model cells and neurons.
Consequently, the spatial learning and memory of 3 * Tg-AD mice were
significantly improved upon Ebselen treatment. This study provides a potential
novel therapeutic approach for the prevention of AD.
PMID- 28502069
TI - Topiramate Therapy in Alternating Hemiplegia of Childhood.
PMID- 28502071
TI - Update from the Abdominal Compartment Society (WSACS) on intra-abdominal
hypertension and abdominal compartment syndrome: past, present, and future beyond
Banff 2017.
PMID- 28502072
TI - The effects of nursing activities on the intra-abdominal pressure of patients at
risk for intra-abdominal hypertension.
AB - BACKGROUND: Intra-abdominal hypertension (IAH) occurs frequently in critically
ill patients, and adds to their morbidity and mortality. There is no published
evidence on the effects of nursing activities on the intra-abdominal pressure
(IAP) for patients at risk of IAH. The purpose of this study was to identify the
effects of hygiene care on the IAP of patients at risk for IAH. METHODS: Hygiene
care was provided to 34 at-risk patients. IAP was measured prior to initiating
the hygiene care, immediately after and 10 minutes later. This was a quasi
experimental, pre-test/ post-test design. RESULTS: The 10 minute post-hygiene
care measurement of the IAP was significantly lower than the pre or immediate
post-measurement of the IAP. There were no significant changes in the mean
arterial pressure (MAP) or the abdominal perfusion pressure (APP). CONCLUSIONS:
It is safe and possibly therapeutic to provide hygiene care to patients at risk
for IAH.
PMID- 28502073
TI - Early impact of abdominal compartment syndrome on liver, kidney and lung damage
in a rodent model.
AB - BACKGROUND: Abdominal compartment syndrome (ACS) sometimes occurs in critically
ill patients following damage control surgery. The purpose of the present study
was to develop a model of ACS and to evaluate its pathologic impact on liver,
kidney, and lung morphology. METHODS: Twenty Wistar rats (mass 300-350 g) were
randomly divided into four groups: 1) intra-abdominal hypertension (IAH): a
laparotomy was performed and the abdomen packed with cotton until an intra
abdominal pressure (IAP) of 15 mm Hg was reached; 2) hypovolemia (HYPO): blood
was withdrawn until a mean arterial pressure ~60 mm Hg was reached; 3) IAH + HYPO
(to resemble clinical ACS); and 4) sham surgery. After 3 hours of protective
mechanical ventilation, the animals were euthanized and the liver, kidney and
lungs removed to examine the degree of tissue damage. RESULTS: IAH resulted in
the following: oedema and neutrophil infiltration in the kidney; necrosis,
congestion, and microsteatosis in the liver; and alveolar collapse, haemorrhage,
interstitial oedema, and neutrophil infiltration in the lungs. Furthermore, IAH
was associated with greater cell apoptosis in the kidney, liver and lungs
compared to sham surgery. HYPO led to oedema and neutrophil infiltration in the
kidney. The combination of IAH and HYPO resulted in all the aforementioned
changes in lung, kidney and liver tissue, as well as exacerbation of the
inflammatory process in the kidney and liver and kidney cell necrosis and
apoptosis. CONCLUSIONS: Intra-abdominal hypertension by itself is associated with
kidney, liver and lung damage; when combined with hypovolemia, it leads to
further impairment and organ damage.
PMID- 28502074
TI - Causes and consequences of mesenteric embolization after endovascular aorto-iliac
intervention - a nested case control study.
AB - BACKGROUND: Causes and consequences of mesenteric embolization after endovascular
aorto-iliac procedures have not been studied adequately. METHODS: Consecutive
patients with mesenteric embolization after endovascular aorto-iliac intervention
between 2011 and 2015 (case-group, n = 9) were investigated and compared with
age, gender and procedure-matched random controls (n = 36). RESULTS: Compared to
the control group, a higher proportion of patients with mesenteric embolization
were current smokers (89% vs. 53%; P = 0.048) and had renal insufficiency at
admission (44% vs. 11%; P = 0.019). In patients treated for aorto-iliac occlusive
disease, aortic irregularity (shagginess) was more severe (P = 0.015), visceral
thrombus volume was larger (P = 0.004) and operation-time was longer (P = 0.009)
among the case-group. However, no differences were found between cases with
mesenteric embolization caused by endovascular aortic aneurysm repair versus
controls. Myoglobin, arterial blood lactate, aspartate aminotransferase, alanine
aminotransferase and pancreatic amylase levels were elevated in 100%, 67%, 89%,
89%, 89% and 56% of patients with mesenteric embolization, respectively. Overall
in-hospital mortality among cases was 33% (3/9). The in-hospital mortality was
17% (1/6) in patients treated with open abdomen therapy, of whom five were
managed with stomas. CONCLUSION: Smoking cessation, careful patient selection and
procedure planning with identification of severe shaggy aortas might prevent
mesenteric embolization during aorto-iliac procedures. In suspected cases of
mesenteric embolization, elevated myoglobin and arterial blood lactate may be
indicative of this complication. Aspartate and alanine aminotranferases, as well
as pancreatic amylase, are also relevant tests to assess the extent of organ
ischaemia. Damage control with open abdomen therapy and the creation of stomas
seem justifiable in order to improve survival in this complex situation.
PMID- 28502070
TI - Sleep in Children with Autism Spectrum Disorder.
AB - The purposes of this paper are to provide an overview of the state of the science
of sleep in children with autism spectrum disorder (ASD), present hypotheses for
the high prevalence of insomnia in children with ASD, and present a practice
pathway for promoting optimal sleep. Approximately two thirds of children with
ASD have chronic insomnia, and to date, the strongest evidence on promoting sleep
is for sleep education, environmental changes, behavioral interventions, and
exogenous melatonin. The Sleep Committee of the Autism Treatment Network (ATN)
developed a practice pathway, based on expert consensus, to capture best
practices for screening, identification, and treatment for sleep problems in ASD
in 2012. An exemplar case is presented to integrate key constructs of the
practice pathway and address arousal and sensory dysregulation in a child with
ASD and anxiety disorder. This paper concludes with next steps for dissemination
of the practice pathway and future directions for research of sleep problems in
ASD.
PMID- 28502076
TI - Scalp threading with polydioxanone monofilament threads: a novel, effective and
safe modality for hair restoration.
PMID- 28502075
TI - Vacuum-assisted wound closure and mesh-mediated fascial traction for open abdomen
therapy - a systematic review.
AB - BACKGROUND: The aim of this paper was to review the literature on vacuum-assisted
wound closure and mesh-mediated fascial traction (VAWCM) in open abdomen therapy.
It was designed as systematic review of observational studies. METHODS: A Pub
Med, EMBASE and Cochrane search from 2007/01-2016/07 was performed combining the
Medical Subject Headings "vacuum", "mesh-mediated fascial traction", "temporary
abdominal closure", "delayed abdominal closure", "open abdomen", "abdominal
compartment syndrome", "negative pressure wound therapy" or "vacuum assisted
wound closure". RESULTS: Eleven original studies were found including patients
numbering from 7 to 111. Six studies were prospective and five were
retrospective. Nine studies were on mixed surgical (n = 9), vascular (n = 6) and
trauma (n = 6) patients, while two were exclusively on vascular patients. The
primary fascial closure rate per protocol varied from 80-100%. The time to
closure of the open abdomen varied between 9-32 days. The entero-atmospheric
fistula rate varied from 0-10.0%. The in-hospital survival rate varied from 57
100%. In the largest prospective study, the incisional hernia rate among
survivors at 63 months of median follow-up was 54% (27/50), and 16 (33%) repairs
out of 48 incisional hernias were performed throughout the study period. The
study patients reported lower short form health survey (SF-36) scores than the
mean reference population, mainly dependent on the prevalence of major co
morbidities. There was no difference in SF-36 scores or a modified ventral hernia
pain questionnaire (VHPQ) at 5 years of follow up between those with versus those
without incisional hernias. CONCLUSIONS: A high primary fascial closure rate can
be achieved with the vacuum-assisted wound closure and meshmediated fascial
traction technique in elderly, mainly non-trauma patients, in need of prolonged
open abdomen therapy.
PMID- 28502077
TI - Life [ageing] is like riding a bicycle. To keep your [coronary and heart] balance
you must keep moving.
PMID- 28502079
TI - Microstructure alterations in the hypothalamus in cranially radiated childhood
leukaemia survivors but not in craniopharyngioma patients unaffected by
hypothalamic damage.
AB - OBJECTIVE: Metabolic complications are frequent in childhood leukaemia (ALL)
survivors treated with cranial radiotherapy (CRT). These complications are
potentially mediated by damage to the hypothalamus (HT), as childhood onset (CO)
craniopharyngioma (CP) survivors without HT involvement are spared overt obesity.
Diffusion tensor imaging (DTI) shows brain tissue microstructure alterations, by
fractional anisotrophy (FA), mean diffusivity (MD), axial diffusivity (AD) and
radial diffusivity (RD). We used DTI to determine the integrity of the
microstructure of the HT in ALL survivors. DESIGN: Case-control study. PATIENTS:
Three groups were included: (i) 27 CRT treated ALL survivors on hormone
supplementation, (ii) 17 CO-CP survivors on hormone supplementation but without
HT involvement and (iii) 27 matched controls. MEASUREMENTS: DTI parameters of the
HT were measured and body composition. RESULTS: Microstructural alterations in
the HT were more severe in ALL survivors with a BMI >=25 than with BMI <25.
Compared to controls, ALL survivors had reduced FA (P=.04), increased MD
(P<.001), AD (P<.001) and RD (P<.001) in the right and left HT. In the right HT,
ALL survivors with a BMI >=25 showed elevated MD (P=.03) and AD (P=.02) compared
to ALL survivors with BMI <25. In contrast, DTI parameters did not differ between
CP survivors and controls. CONCLUSIONS: Long-term follow-up after CRT for ALL DTI
measures were affected in the HT despite complete hormone replacement. The
present data suggest that ALL survivors have demyelination and axonal loss in the
HT.
PMID- 28502078
TI - Dual-specificity tyrosine-regulated kinase 2 is a suppressor and potential
prognostic marker for liver metastasis of colorectal cancer.
AB - Colorectal cancer is a common cancer and a leading cause of cancer-related death
worldwide. The liver is a dominant metastatic site for patients with colorectal
cancer. Molecular mechanisms that allow colorectal cancer cells to form liver
metastases are largely unknown. Activation of epithelial-mesenchymal transition
is the key step for metastasis of cancer cells. We recently reported that dual
specificity tyrosine-regulated kinase 2 (DYRK2) controls epithelial-mesenchymal
transition in breast cancer and ovarian serous adenocarcinoma. The aim of this
study is to clarify whether DYRK2 regulates liver metastases of colorectal
cancer. We show that the ability of cell invasion and migration was abrogated in
DYRK2-overexpressing cells. In an in vivo xenograft model, liver metastatic
lesions were markedly diminished by ectopic expression of DYRK2. Furthermore, we
found that patients whose liver metastases expressed low DYRK2 levels had
significantly worse overall and disease-free survival. Given the findings that
DYRK2 regulates cancer cell metastasis, we concluded that the expression status
of DYRK2 could be a predictive marker for liver metastases of colorectal cancer.
PMID- 28502080
TI - Contemporary role of ureterolysis in retroperitoneal fibrosis: treatment of last
resort or first intent? An analysis of 50 cases.
AB - OBJECTIVE: To determine the outcomes of open ureterolysis in a contemporary
cohort of patients presenting with ureteric obstruction secondary to
retroperitoneal fibrosis (RPF). PATIENTS AND METHODS: We conducted a prospective
analysis of 50 patients undergoing open ureterolysis and omental wrap between
January 2012 and January 2016 in a single centre, managed by a multi-disciplinary
RPF team. Patients had a minimum follow-up of 1 year. Indications were:
nephrostomy-dependent drainage (n = 5); stent failure as evidenced by persistent
hydronephrosis (n = 20); severe stent symptoms (n = 22); and patient choice/pre
emptive (n = 3). Outcome measures were stent-free rate; change in renal function
post-ureterolysis; operating variables (operating time, blood loss,
complications, length of hospital stay); and need for further intervention.
RESULTS: Of the 50 patients, 48 (96%) were stent-free at 3 months and 47/50 (94%)
were stent-free at 12 months. The median (interquartile range [IQR]) changes in
glomerular filtration rate, according to these indication groups, at 1 year were:
overall +6 (-4 to +22)% (P < 0.05); stent failure +25 (+5 to +27)% (P < 0.001);
stent symptoms +0 (-17 to +6)% (P = 0.834); nephrostomy-dependent drainage -10 (
19 to -2)% (P = 0.731); and pre-emptive 0 (0 to +8)% (P = 0.5). A total of 11/50
patients (22%) underwent additional procedures: nephrectomy, n = 7; uretero
ureterostomy, n = 1; aneurysm repair, n = 1; 1 Boari flap, n = 1; and ureteric re
implant, n = 1. Serious complications (Clavien III or IV) occurred in 12% of
patients. The median (IQR) blood loss was 390 (20-1,200) mL and the median (IQR)
length of hospital stay was 8 (3-21) days. CONCLUSIONS: This study suggests that
for patients with ureteric obstruction caused by RPF, contemporary ureterolysis
performed by a high-volume specialist team can successfully render patients stent
or nephrostomy-free without compromising renal function. The results suggest
that ureterolysis should be considered in all patients who present with ureteric
obstruction caused by RPF that does not respond quickly to standard treatment.
PMID- 28502081
TI - Simultaneous modification of three homoeologs of TaEDR1 by genome editing
enhances powdery mildew resistance in wheat.
AB - Wheat (Triticum aestivum L.) incurs significant yield losses from powdery mildew,
a major fungal disease caused by Blumeria graminis f. sp. tritici (Bgt). enhanced
disease resistance1 (EDR1) plays a negative role in the defense response against
powdery mildew in Arabidopsis thaliana; however, the edr1 mutant does not show
constitutively activated defense responses. This makes EDR1 an ideal target for
approaches using new genome-editing tools to improve resistance to powdery
mildew. We cloned TaEDR1 from hexaploid wheat and found high similarity among the
three homoeologs of EDR1. Knock-down of TaEDR1 by virus-induced gene silencing or
RNA interference enhanced resistance to powdery mildew, indicating that TaEDR1
negatively regulates powdery mildew resistance in wheat. We used CRISPR/Cas9
technology to generate Taedr1 wheat plants by simultaneous modification of the
three homoeologs of wheat EDR1. No off-target mutations were detected in the
Taedr1 mutant plants. The Taedr1 plants were resistant to powdery mildew and did
not show mildew-induced cell death. Our study represents the successful
generation of a potentially valuable trait using genome-editing technology in
wheat and provides germplasm for disease resistance breeding.
PMID- 28502082
TI - Desynchronizations in bee-plant interactions cause severe fitness losses in
solitary bees.
AB - Global warming can disrupt mutualistic interactions between solitary bees and
plants when increasing temperature differentially changes the timing of
interacting partners. One possible scenario is for insect phenology to advance
more rapidly than plant phenology. However, empirical evidence for fitness
consequences due to temporal mismatches is lacking for pollinators and it remains
unknown if bees have developed strategies to mitigate fitness losses following
temporal mismatches. We tested the effect of temporal mismatches on the fitness
of three spring-emerging solitary bee species, including one pollen specialist.
Using flight cages, we simulated (i) a perfect synchronization (from a bee
perspective): bees and flowers occur simultaneously, (ii) a mismatch of 3 days
and (iii) a mismatch of 6 days, with bees occurring earlier than flowers in the
latter two cases. A mismatch of 6 days caused severe fitness losses in all three
bee species, as few bees survived without flowers. Females showed strongly
reduced activity and reproductive output compared to synchronized bees. Fitness
consequences of a 3-day mismatch were species-specific. Both the early-spring
species Osmia cornuta and the mid-spring species Osmia bicornis produced the same
number of brood cells after a mismatch of 3 days as under perfect
synchronization. However, O. cornuta decreased the number of female offspring,
whereas O. bicornis spread the brood cells over fewer nests, which may increase
offspring mortality, e.g. due to parasitoids. The late-spring specialist Osmia
brevicornis produced fewer brood cells even after a mismatch of 3 days.
Additionally, our results suggest that fitness losses after temporal mismatches
are higher during warm than cold springs, as the naturally occurring temperature
variability revealed that warm temperatures during starvation decreased the
survival rate of O. bicornis. We conclude that short temporal mismatches can
cause clear fitness losses in solitary bees. Although our results suggest that
bees have evolved species-specific strategies to mitigate fitness losses after
temporal mismatches, the bees were not able to completely compensate for impacts
on their fitness after temporal mismatches with their food resources.
PMID- 28502084
TI - Conspecific and not performance-based attraction on immigrants drives colony
growth in a waterbird.
AB - Local recruitment and immigration play an important part in the dynamics and
growth of animal populations. However, their estimation and incorporation into
open population models is, in most cases, problematic. We studied factors
affecting the growth of a recently established colony of Eurasian spoonbill
(Platalea leucorodia) and assessed the contribution of local recruits, i.e. birds
born in the colony, and immigrants, i.e. birds of unknown origin, to colony
growth. We applied an integrated population model that accounts for uncertainty
in breeding state assignment and merges population surveys, local fecundity and
individual longitudinal data of breeding and non-breeding birds, to estimate
demographic rates and the relative role of recruitment and immigration in driving
the local dynamics. We also used this analytical framework to assess the degree
of support for the 'performance-based' and 'conspecific attraction' hypotheses as
possible mechanisms of colony growth. Among the demographic rates, only
immigration was positively and significantly correlated with population growth
rate. In addition, the number of immigrants settling in the colony was positively
correlated with colony size in the previous and current year, but was not
correlated with fecundity of the previous year. Our results suggest that the
variation in immigration affected colony dynamics and that conspecific attraction
likely triggered the relevant role of immigration in the growth of a recently
formed waterbird colony, supporting the need of including immigration in
population analysis.
PMID- 28502083
TI - In vivo microvascular imaging of cutaneous actinic keratosis, Bowen's disease and
squamous cell carcinoma using dynamic optical coherence tomography.
AB - BACKGROUND: A clear distinction between actinic keratosis (AK), Bowen's disease
(BD) and squamous cell carcinoma (SCC) cannot reliably be made by clinical and
dermoscopic evaluation alone. Dynamic optical coherence tomography (D-OCT) is a
novel angiographic variant of OCT that allows for non-invasive, in vivo
evaluation of the cutaneous microvascular morphology. OBJECTIVE: To investigate
the microvascular structures of AK, BD and invasive SCC using D-OCT in order to
gain insights into the microvascular morphology of lesions in the spectrum of
keratinocyte skin cancers. METHODS: Forty-seven patients with a total of 54
lesions (18 AK, 12 BD and 24 SCC) were included in the study. D-OCT still images
of AK, BD and SCC at three predefined skin depths were prepared and randomized,
creating a study set of 162 D-OCT images. Three observers performed blinded
evaluations of the randomized study set assessing multiple parameters including
the different types of vascular morphology. Non-blinded quantitative measurements
of vascular diameter were also performed. RESULTS: The blinded observer analysis
suggests that D-OCT evaluation of the vascular morphology may aid in
distinguishing AK, BD and SCC lesions. We identified two vascular shapes that
presented significantly differently across the lesion types, namely 'blobs' and
'curves'. A strong presence of blobs at 300 MUm skin depth was characteristically
seen in a third of BD cases, while not or only slightly present in AK and SCC
lesions. Vascular curves were predominantly present in AK lesions. CONCLUSION: We
identified various vascular D-OCT features that may aid in non-invasively
differentiating subtypes within the keratinocyte skin cancer spectrum.
PMID- 28502085
TI - Pathogenicity of ADAR1 mutation in a Chinese family with dyschromatosis
symmetrica hereditaria.
PMID- 28502087
TI - Palmar melanoma: a tertiary centre experience.
PMID- 28502086
TI - Does influenza pandemic preparedness and mitigation require gain-of-function
research?
AB - The risk and benefits of gain-of-function studies on influenza A have been widely
debated since 2012 when the methods to create two respiratory transmissible H5N1
mutant isolates were published. Opponents of gain-of-function studies argue the
biosecurity risk is unacceptable, while proponents cite potential uses for
pandemic surveillance, preparedness and mitigation. In this commentary, we
provide an overview of the background and applications of gain-of-function
research and argue that the anticipated benefits have yet to materialize while
the significant risks remain.
PMID- 28502088
TI - Limited impact of awareness-raising campaigns on hepatitis C testing practices
among general practitioners.
AB - The global hepatitis strategy calls for increased effort to diagnose those
infected, with a target of 90% diagnosed by 2030. Scotland's Action Plan on
Hepatitis C included awareness-raising campaigns, undertaken during 2008-2011, to
promote testing by general practitioners. We examined hepatitis C virus (HCV)
testing practice among general practitioners before and following these
campaigns. Scottish general practitioners were surveyed, using Dillman's method,
in 2007 and 2013; response rates were 69% and 60%, respectively. Most respondents
offer testing when presented with a risk history (86% in 2007, 88% in 2013) but
only one-fifth actively sought out risk factors (19% in 2007, 21% in 2013).
Testing was reportedly always/almost always/usually offered to people who inject
drugs (84% in 2007, 87% in 2013). Significant improvements in the offer of
testing were reported in patients with abnormal LFTs (41% in 2007, 65% in 2013,
P<.001) and who had received medical/dental treatment in high prevalence
countries (14% in 2007, 24% in 2013, P=.001). In 2013, 25% of respondents had
undertaken HCV-related continued professional development. This group was
significantly more likely to actively seek out risk factors (P=.009) but only
significantly more likely to offer a test to patients who had received
medical/dental treatment in high prevalence countries (P=.001). Our findings
suggest that government-led awareness raising campaigns have limited impact on
general practitioners' testing practices. If the majority of the HCV-infected
population are to be diagnosed, practitioner-based or physician-centred
interventions should be considered alongside educational initiatives targeted at
professionals.
PMID- 28502090
TI - Successful use of lipid emulsion to resuscitate a foal after intravenous
lidocaine induced cardiovascular collapse.
AB - BACKGROUND: Lipid emulsion has been reported to be effective for the treatment of
local anaesthetic overdoses in rats, dogs and man. OBJECTIVES: To describe the
successful treatment of cardiovascular lidocaine toxicity in a foal with
intravenous lipid administration. STUDY DESIGN: Observational study: case report.
METHODS: An 8-month-old Arabian cross foal was anaesthetised for removal of the
right alar fold and nasal plate. Anaesthesia was maintained with isoflurane in
oxygen and lidocaine administered with a loading dose followed by a continuous
rate infusion (CRI). The anaesthetic period was uneventful and 30 min before
expected termination of the procedure lidocaine infusion was stopped. A sudden
drop in mean arterial blood pressure was then observed. The ECG signal was lost,
the end tidal CO2 tension dropped from 40 to 10 mmHg, corneal reflex was absent
and asystole diagnosed. Cardiopulmonary resuscitation manoeuvres were immediately
initiated, but epinephrine and atropine were unsuccessfully administered. Lipid
emulsion was administered and the heart rate and arterial blood pressure
gradually returned to normal. RESULTS: The foal recovered consciousness 3 h
later, regained its sternal position, was responsive and 20 h later was able to
stand up alone. MAIN LIMITATIONS: It will be necessary to evaluate a greater
number of cases to determine the effectiveness of lipids in foals intoxicated
with lidocaine. CONCLUSION: Intravenous lipid emulsion may be helpful in the
treatment of potentially lethal cardiotoxicity attributable to lidocaine overdose
in the foal.
PMID- 28502089
TI - Association between cytokine profile and transcription factors produced by T-cell
subsets in early- and late-onset pre-eclampsia.
AB - Pre-eclampsia (PE) is an obstetric pathology characterized by abnormal activation
of the innate and adaptive immune systems dependent on the imbalance of T helper
subsets. The present study aimed to evaluate the gene and protein expression of T
helper type 1 (Th1)/Th2/Th17/regulatory T (Treg) cell transcription factors in
peripheral blood lymphocytes from pregnant women with PE employing quantitative
RT-PCR and flow cytometry techniques, as well as the cytokine profile produced by
these CD4+ T-cell subsets in the plasma of pregnant women with PE, classified as
early-onset PE (n = 20), late-onset PE (n = 20) and normotensive pregnant women
(n = 20). Results showed a higher percentage of CD4+ T cells expressing the RORc
transcription factor (Th17) and a lower percentage of cells expressing FoxP3
(Treg) in women with early-onset PE compared with late-onset PE and normotensive
groups. A lower gene expression of GATA-3 transcription factor was detected in
cells of women with early-onset PE compared with the late-onset PE group.
Endogenous plasma levels of interleukin-6 (IL-6), IL-17 and tumour necrosis
factor-alpha were significantly higher in the early-onset PE group than in the
late-onset PE and normotensive groups, whereas IL-4 (Th2 profile) and IL-22 (Th17
profile), were not significantly different between the studied groups. The
endogenous levels of transforming growth factor-beta and IL-10 were significantly
lower in the pre-eclamptic than in the normotensive groups of the same
gestational age, with a significant difference between early- and late-onset PE.
The results show that in women with PE there is an imbalance between inflammatory
and anti-inflammatory profiles in CD4+ T-cell subsets, with polarization to Th17
profiles in the early-onset PE, considered as the severe form of PE.
PMID- 28502092
TI - HIV/HCV coinfection and the risk of cardiovascular disease: A meta-analysis.
AB - The emergence of improved antiretroviral therapy has increased the life
expectancy of human immunodeficiency virus (HIV)-infected individuals, although
there is an increased susceptibility to developing cardiovascular diseases (CVD).
The risk for CVD is purported to be even higher among people with HIV and
hepatitis C virus (HCV) coinfection because of the increased inflammatory
response, which may synergistically impact CVD risk. However, studies comparing
CVD outcomes between HIV alone and HIV/HCV individuals have been discordant.
Accordingly, we conducted a meta-analysis to clarify and quantify the association
between HIV/HCV coinfection and the risk for CVD. We searched EMBASE, CINAHL,
Google Scholar, PubMed, and Web of Science from inception to December 2016 to
identify studies that provided information on HIV/HCV coinfection and CVD,
defined as coronary artery disease, congestive heart failure and stroke. We used
a random-effects model to abstract and pool data on the hazard ratios (HRs) for
CVD. HRs were adjusted for traditional CVD risk factors including age, sex,
smoking, hypertension, diabetes and LDL cholesterol. Among the 283 articles
reviewed, four cohort studies met inclusion criteria with a total of 33 723
participants. The pooled adjusted HRs for the association between HIV/HCV
coinfection and CVD were 1.24 (95% CI: 1.07-1.40) compared to HIV monoinfection.
The test for heterogeneity was not statistically significant (I2 =0.0%, P=.397).
In conclusion, individuals with HIV/HCV coinfection had an increased CVD risk
compared to those with HIV monoinfection. More research is needed to further
examine the nature of this association, and response to traditional risk
reduction therapies.
PMID- 28502091
TI - Increased Pretransplant Frequency of CD28+ CD4+ TEM Predicts Belatacept-Resistant
Rejection in Human Renal Transplant Recipients.
AB - While most human T cells express the CD28 costimulatory molecule constitutively,
it is well known that age, inflammation, and viral infection can drive the
generation of CD28null T cells. In vitro studies have demonstrated that CD28null
cell effector function is not impacted by the presence of the CD28 costimulation
blocker belatacept. As such, a prevailing hypothesis suggests that CD28null cells
may precipitate costimulation blockade-resistant rejection. However, CD28+ cells
possess more proliferative and multifunctional capacity, factors that may
increase their ability to successfully mediate rejection. Here, we performed a
retrospective immunophenotypic analysis of adult renal transplant recipients who
experienced acute rejection on belatacept treatment as compared to those who did
not. Intriguingly, our findings suggest that patients possessing higher frequency
of CD28+ CD4+ TEM prior to transplant were more likely to experience acute
rejection following treatment with a belatacept-based immunosuppressive regimen.
Mechanistically, CD28+ CD4+ TEM contained significantly more IL-2 producers. In
contrast, CD28null CD4+ TEM isolated from stable belatacept-treated patients
exhibited higher expression of the 2B4 coinhibitory molecule as compared to those
isolated from patients who rejected. These data raise the possibility that
pretransplant frequencies of CD28+ CD4+ TEM could be used as a biomarker to
predict risk of rejection following treatment with belatacept.
PMID- 28502094
TI - PD-L1 overexpression in ampulla of Vater carcinoma and its pre-invasive lesions.
AB - AIMS: PD-1/PD-L1 checkpoint immunotherapy has been proposed recently as a
promising treatment in relapsed/refractory disease, used eventually in
combination with traditional chemotherapy in different cancer settings. To date,
no data are available concerning PD-L1 expression in ampulla of Vater carcinoma
and its pre-invasive lesions. METHODS AND RESULTS: We assessed the
immunohistochemical expression of PD-L1 in a series of 26 ampullary
adenocarcinomas, 50 ampullary dysplastic lesions and 10 normal duodenal mucosa
samples. Moreover, in all cases DNA mismatch repair proteins status was
investigated. PD-L1 was expressed in seven of 26 (26.9%) invasive carcinomas and
three of 50 (6.0%) dysplastic samples. Most of the PD-L1-positive tumours (seven
of 10) were intestinal-type and poorly differentiated (G3). The number of PD-L1
positive stromal lymphoid cells was significantly higher in dysplastic and
invasive lesions than in the normal samples (P = 0.011). Nineteen dysplastic
lesions and eight invasive carcinomas did not show any evident epithelial or
stromal PD-L1 expression. Four of the carcinomas were mismatch repair-deficient
and two of these were PD-L1-positive. Furthermore, mismatch repair-deficient
lesions showed a significantly higher average of PD-L1-positive stromal lymphoid
cells than those of neoplastic PD-L1-negative samples (62.8 versus 21.6; P <
0.001). CONCLUSIONS: The present results suggest a role of the PD-1/PD-L1 axis in
ampullary adenocarcinomas, and therefore this may also prompt consideration of
checkpoint immunotherapy as a novel promising treatment for these tumours.
PMID- 28502096
TI - Circumscribed palmoplantar hypokeratosis: successful treatment with the 10 600-nm
carbon dioxide fractional laser.
PMID- 28502093
TI - The TLR4-TRIF pathway can protect against the development of experimental
allergic asthma.
AB - The Toll-like receptor (TLR) adaptor proteins myeloid differentiating factor 88
(MyD88) and Toll, interleukin-1 receptor and resistance protein (TIR) domain
containing adaptor inducing interferon-beta (TRIF) comprise the two principal
limbs of the TLR signalling network. We studied the role of these adaptors in the
TLR4-dependent inhibition of allergic airway disease and induction of CD4+ ICOS+
T cells by nasal application of ProtollinTM, a mucosal adjuvant composed of TLR2
and TLR4 agonists. Wild-type (WT), Trif-/- or Myd88-/- mice were sensitized to
birch pollen extract (BPEx), then received intranasal Protollin followed by
consecutive BPEx challenges. Protollin's protection against allergic airway
disease was TRIF-dependent and MyD88-independent. TRIF deficiency diminished the
CD4+ ICOS+ T-cell subsets in the lymph nodes draining the nasal mucosa, as well
as their recruitment to the lungs. Overall, TRIF deficiency reduced the
proportion of cervical lymph node and lung CD4+ ICOS+ Foxp3- cells, in
particular. Adoptive transfer of cervical lymph node cells supported a role for
Protollin-induced CD4+ ICOS+ cells in the TRIF-dependent inhibition of airway
hyper-responsiveness. Hence, our data demonstrate that stimulation of the TLR4
TRIF pathway can protect against the development of allergic airway disease and
that a TRIF-dependent adjuvant effect on CD4+ ICOS+ T-cell responses may be a
contributing mechanism.
PMID- 28502095
TI - The impact of age and frailty on ventricular structure and function in C57BL/6J
mice.
AB - KEY POINTS: Heart size increases with age (called hypertrophy), and its ability
to contract declines. However, these reflect average changes that may not be
present, or present to the same extent, in all older individuals. That aging
happens at different rates is well accepted clinically. People who are aging
rapidly are frail and frailty is measured with a 'frailty index'. We quantified
frailty with a validated mouse frailty index tool and evaluated the impacts of
age and frailty on cardiac hypertrophy and contractile dysfunction. Hypertrophy
increased with age, while contractions, calcium currents and calcium transients
declined; these changes were graded by frailty scores. Overall health status,
quantified as frailty, may promote maladaptive changes associated with cardiac
aging and facilitate the development of diseases such as heart failure. To
understand age-related changes in heart structure and function, it is essential
to know both chronological age and the health status of the animal. ABSTRACT: On
average, cardiac hypertrophy and contractile dysfunction increase with age.
Still, individuals age at different rates and their health status varies from fit
to frail. We investigated the influence of frailty on age-dependent ventricular
remodelling. Frailty was quantified as deficit accumulation in adult (~7 months)
and aged (~27 months) C57BL/6J mice by adapting a validated frailty index (FI)
tool. Hypertrophy and contractile function were evaluated in Langendorff-perfused
hearts; cellular correlates/mechanisms were investigated in ventricular myocytes.
FI scores increased with age. Mean cardiac hypertrophy increased with age, but
values in the adult and aged groups overlapped. When plotted as a function of
frailty, hypertrophy was graded by FI score (r = 0.67-0.55, P < 0.0003). Myocyte
area also correlated positively with FI (r = 0.34, P = 0.03). Left ventricular
developed pressure (LVDP) plus rates of pressure development (+dP/dt) and decay (
dP/dt) declined with age and this was graded by frailty (r = -0.51, P = 0.0007; r
= -0.48, P = 0.002; r = -0.56, P = 0.0002 for LVDP, +dP/dt and -dP/dt). Smaller,
slower contractions graded by FI score were also seen in ventricular myocytes.
Contractile dysfunction in cardiomyocytes isolated from frail mice was
attributable to parallel changes in underlying Ca2+ transients. These changes
were not due to reduced sarcoplasmic reticulum stores, but were graded by smaller
Ca2+ currents (r = -0.40, P = 0.008), lower gain (r = -0.37, P = 0.02) and
reduced expression of Cav1.2 protein (r = -0.68, P = 0.003). These results show
that cardiac hypertrophy and contractile dysfunction in naturally aging mice are
graded by overall health and suggest that frailty, in addition to chronological
age, can help explain heterogeneity in cardiac aging.
PMID- 28502097
TI - Oral health-related quality of life and risk factors associated with traumatic
dental injuries in Brazilian children: A multilevel approach.
AB - BACKGROUND/AIMS: Among the diseases related to oral health, such as caries and
oral cancer, dental trauma stands out as one of the major public health problems
worldwide. The aim of this study was to verify the occurrence of factors
associated with traumatic dental injuries (TDIs), including oral health-related
quality of life (OHRQoL), sociodemographic characteristics, untreated caries,
occlusal problems and contextual variables in 12-year-old Brazilian children.
METHODS: This study assessed a complex sample of the National Research in Oral
Health (SBBrasil 2010) data on 7240 12-year-old children and contextual features
of the municipalities where they lived. RESULTS: TDI prevalence in 12-year-old
schoolchildren was 23.96%. Being female was a protective factor for all trauma
outcome variables. Non-white children were at risk of maxillary tooth fractures.
Maxillary overjet greater than 3 mm was associated with all trauma outcomes.
Crowding and spacing were risk factors for enamel trauma. TDI has a negative
impact on OHRQoL. None of the contextual variables analysed (Gini coefficient,
MHDI, family health strategy and water fluoridation) were associated with TDI in
the multilevel approach. CONCLUSIONS: TDI was better explained by individual
factors, related to sociodemographic conditions and occlusal problems, with a
negative impact on OHRQoL, adjusted for untreated caries. Contextual variables
were not associated with TDI in 12-year-old Brazilian schoolchildren.
Interdisciplinary actions for preventing dental trauma, such as stimulating the
use of mouthguards, have to be encouraged by the family health strategy (FHS) and
school health programme (SHP).
PMID- 28502098
TI - "Fix Me Another Marguerite!": Species delimitation in a group of intensively
hybridizing lineages of ox-eye daisies (Leucanthemum Mill., Compositae
Anthemideae).
AB - Delineating species boundaries in the framework of the multi-species coalescent
(MSC) proves to be a reliable, objective, and reproducible method in an
increasing number of studies. However, the underlying model assumes the lack of
gene flow after speciation; an assumption which may be frequently violated in
plant evolution. This study evaluates the robustness of currently available
species delimitation methods implemented in beast (BFD, BFD*, and dissect) in the
closely-knit ox-eye daisy group around Leucanthemum ageratifolium Pau. Comprising
five taxa being allopatrically distributed between northern Spain and southern
Italy this study group shows signs of hybridization with the widespread and
codistributed species Leucanthemum vulgare (Vaill.) Lam. to various extent. As
expected, our empirical analyses based on both AFLP fingerprinting and sequence
data demonstrate that the robustness of species delimitation results is
considerably influenced by the intensity of hybridization among species and the
number of hybrid individuals included. Therefore, we set up a methodological
pipeline with a first step of identification and subsequent removal of
individuals showing admixed genetic patterns caused by actual interbreeding using
AFLP-fingerprint and morphometric data, followed by application of different
Bayesian MSC species delimitation methods based on the remnant individuals using
both AFLP-fingerprint and sequence data (four nuclear markers, five concatenated
intergenic spacer regions of the plastid genome). The results argue for
acknowledgement of Leucanthemum laciniatum, L. legraeanum, and L. ligusticum as
independent species, show the close relationship of L. ageratifolium, L.
monspeliense, and L. vulgare, and give rise to the description of three
nothospecies new to science.
PMID- 28502100
TI - HER2 FISH results in breast cancers with increased CEN17 signals using
alternative chromosome 17 probes - reclassifying cases in the equivocal category.
AB - AIMS: HER2 testing of invasive breast cancer by in-situ hybridization guides
therapy decisions. Probing HER2 and centromere of chromosome 17 (cen17)
simultaneously is supposed to reveal both a potential HER2 gene amplification and
polysomy 17. However, a considerable number of breast cancer patients with quasi
polysomy 17 are considered 'equivocal', which is diagnostically meaningless.
Moreover, patients with equivocal/false polysomic tumours are prevented from a
potentially beneficial anti-HER2 treatment. Here we evaluated the RAI1, D17S122
and TP53 hybridization markers to indicate true polysomy reliably and to
reclassify equivocal samples accurately as HER2-positive. METHODS AND RESULTS:
Samples with (n = 82) and without (n = 52) increased cen17 copy numbers and 78
evidently HER2-amplified specimens were analysed using dual and triple marker
hybridization probes. Selected putative polysomic samples were subjected to array
based comparative genomic hybridization (aCGH). We found that 37.8% samples with
putative polysomy 17 did not show any gain in RAI1, D17S122 or TP53. Accordingly,
aCGH revealed evidence for the presence of HER2/cen17 co-amplification rather
than for true polysomy in those cases. Reflex testing using alternate 17p markers
reclassified up to 56.3% equivocal cases as HER2-positive and the combined
assessment of a 17p and 17q locus allows the differentiation of true versus false
polysomy. CONCLUSIONS: An increased cen17 copy number does not necessarily
reflect polysomy, and reflex testing facilitates the reclassification of
'equivocals'. Nevertheless, the prognostic and predictive value of a HER2/cen17
co-amplification versus HER2 gene amplification alone must still be evaluated
prospectively.
PMID- 28502099
TI - International trends in clozapine use: a study in 17 countries.
AB - OBJECTIVE: There is some evidence that clozapine is significantly underutilised.
Also, clozapine use is thought to vary by country, but so far no international
study has assessed trends in clozapine prescribing. Therefore, this study aimed
to assess clozapine use trends on an international scale, using standardised
criteria for data analysis. METHOD: A repeated cross-sectional design was applied
to data extracts (2005-2014) from 17 countries worldwide. RESULTS: In 2014,
overall clozapine use prevalence was greatest in Finland (189.2/100 000 persons)
and in New Zealand (116.3/100 000), and lowest in the Japanese cohort (0.6/100
000), and in the privately insured US cohort (14.0/100 000). From 2005 to 2014,
clozapine use increased in almost all studied countries (relative increase: 7.8
197.2%). In most countries, clozapine use was highest in 40-59-year-olds (range:
0.6/100 000 (Japan) to 344.8/100 000 (Finland)). In youths (10-19 years),
clozapine use was highest in Finland (24.7/100 000) and in the publicly insured
US cohort (15.5/100 000). CONCLUSION: While clozapine use has increased in most
studied countries over recent years, clozapine is still underutilised in many
countries, with clozapine utilisation patterns differing significantly between
countries. Future research should address the implementation of interventions
designed to facilitate increased clozapine utilisation.
PMID- 28502101
TI - Identification of somatic TERT promoter mutations in familial nonmedullary
thyroid carcinomas.
AB - OBJECTIVE: The genes causing familial nonmedullary thyroid carcinoma (FNMTC)
identified to date are only involved in a small fraction of the families.
Recently, somatic mutations in TERT promoter region and in EIF1AX gene were
reported in thyroid tumours of undefined familial status. The aim of this study
was to investigate the role of TERT and EIF1AX mutations in familial thyroid
tumours. DESIGN: The promoter region of TERT was sequenced in leucocyte DNA of
the probands from 75 FNMTC families. In thyroid tumours from 54 familial cases,
we assessed somatic TERT promoter, RAS and BRAF hotspot mutations, and the whole
EIF1AX gene. RESULTS: No potentially pathogenic germline variants were identified
in TERT in the 75 FNMTC families' probands. In the 54 carcinomas, we identified
five cases (9%) with hotspot somatic TERT promoter mutations. BRAF mutations were
found in 41% of the tumours. All TERT-positive samples were also positive for
BRAF p.Val600Glu, and this co-occurrence was found to be statistically
significant (P=.008). RAS mutations were detected in four tumours wild-type for
TERT (7%). Evaluation of tumour mutation data together with the patients'
clinicopathological features revealed a significant correlation between TERT plus
BRAF mutations and advanced tumour stage (T4) (P=.020). No mutations were
identified in EIF1AX. CONCLUSIONS: The results of this study suggest that TERT
promoter and EIF1AX mutations are not frequently involved in FNMTC aetiology.
However, we show for the first time that TERT alterations are associated with
familial thyroid tumour progression. Our data also suggest that TERT mutations
are more often found in concomitance with BRAF mutations in advanced stages of
FNMTC.
PMID- 28502102
TI - Functional analysis by minigene assay of putative splicing variants found in
Bardet-Biedl syndrome patients.
AB - Bardet-Biedl syndrome (BBS) and Alstrom syndrome (ALMS) are rare diseases
belonging to the group of ciliopathies. Although mutational screening studies of
BBS/ALMS cohorts have been extensively reported, little is known about the
functional effect of those changes. Thus, splicing variants are estimated to
represent 15% of disease-causing mutations, and there is growing evidence that
many exonic changes are really splicing variants misclassified. In this study, we
aimed to analyse for the first time several variants in BBS2, ARL6/BBS3, BBS4 and
ALMS1 genes predicted to produce aberrant splicing by minigene assay. We found
discordance between bioinformatics analysis and experimental data when comparing
wild-type and mutant constructs. Remarkably, we identified nonsense variants
presumably resistant to nonsense-mediated decay, even when a premature
termination codon would be introduced in the second amino acid (p.(G2*) mutation
in ARL6/BBS3 gene). As a whole, we report one of the first functional studies of
BBS/ALMS1 variants using minigene assay, trying to elucidate their role in
disease. Functional studies of variants identified in BBS and ALMS patients are
essential for their proper classification and subsequent genetic counselling and
could also be the start point for new therapeutic approaches, currently based
only on symptomatic treatment.
PMID- 28502103
TI - Reduced platelet aggregation in women after intercourse: a possible role for the
cyclooxygenase pathway.
AB - We hypothesise that molecules in the cyclooxygenase pathway affect platelet
activity when seminal fluid (SF) is present. We considered the influence of SF on
platelet aggregation in women, and believe that the prostanoids in SF signalling
are significant. Thirty-one female subjects were studied, 20 of whom were
sexually active. Male partners were given either aspirin or indomethacin to
inhibit cyclooxygenase. The 6-keto prostaglandin F1alpha (6-keto PGF1alpha) and
prostaglandin E metabolite (PGE-M) in SF were measured by competitive assay.
Platelets and prostanoids were evaluated in women, periodically, before and after
intercourse. The platelets were tested with adenosine diphosphate (ADP) and
arachidonic acid (AA). To block the interaction between the uterus and SF, some
couples used condoms. We found that the 6-keto prostaglandin F1alpha in urine at
2 hours post-intercourse (1418.75 pg/mL, Std 688.39) was greater than pre
intercourse (772.68 pg/mL, Std 116.54). Post-intercourse, a transient decrease in
platelet aggregation was observed in women whose partners did not use condoms.
Averages for platelet aggregation were 20.16% with ADP, and more significantly,
37.79% with AA after 2 hours. In contrast, couples using condoms showed no
changes, averaging 64.02% with ADP and 72.06% with AA. Women whose partners were
taking aspirin or indomethacin also showed no changes. SF from men taking aspirin
or indomethacin led to no reduction in platelet aggregometry in their partners.
These results indicate that in cases of exposure to SF, the transient change in
women's platelet activity could be related to the cyclooxygenase pathway.
PMID- 28502104
TI - Assessing Pain Intensity Using Photoplethysmography Signals in Chronic Myofascial
Pain Syndrome.
AB - BACKGROUND: Efficacy of pain assessment is the basis for effective therapy.
Clinically, assessing pain is by subjective scale, but these methods have some
shortcomings. Therefore, studies have been conducted on assessment of pain using
physiological signals. Photoplethysmography (PPG) signals provide much
information about the cardiovascular system. PPG-derived parameters (PPG
parameters) reflect nociceptive stimulation, and obtain an approximation of the R
R interval from the PPG period. The aim of this study was to evaluate PPG signals
for assessment of pain intensity in chronic myofascial pain syndrome (MPS)
patients. METHODS: This study recruited 37 patients with chronic MPS; all of them
were treated with electrotherapy and thermotherapy. The difference between pre-
and post-therapy PPG parameters, and the correlation between pulse rate
variability (PRV) and heart rate variability (HRV) were determined. We also
obtained patients' pain intensity scores by visual analog scale, visual rating
scale, and Wong-Banker face pain rating scale. RESULTS: Photoplethysmography and
PRV/HRV parameters showed significant differences between pre- and post
treatment. The variation trend of PRV was similar with HRV in heart rate, R-R
interval, low frequency, high frequency, and LF/HF; in addition, a high
correlation between the parameters was observed either in pre- or post-therapy.
PPG parameters indicated increased sympathetic tone. CONCLUSION: The results of
the study indicated that PRV substituted for HRV in assessment of pain intensity
in chronic MPS reflected parasympathetic nervous tone increase, and PPG
parameters might reflect stress stimulation on skin.
PMID- 28502106
TI - Misoprostol for cervical priming prior to office hysteroscopy works in
premenopausal nulliparous but not in postmenopausal women.
PMID- 28502105
TI - Longitudinal changes in serum 25-hydroxyvitamin D in the Dallas Heart Study.
AB - CONTEXT: While the prevalence of vitamin D deficiency is well described in
various populations, limited data are available regarding longitudinal variation
in serum 25-hydroxyvitamin D concentrations. OBJECTIVES: To evaluate the temporal
trends in serum 25(OH)D, prevalence of vitamin D deficiency and factors
influencing these trends. PARTICIPANTS, DESIGN AND SETTING: Adults enrolled in
the Dallas Heart Study, a longitudinal, probability-based, multiethnic,
population study in Dallas, Texas, USA. MAIN OUTCOME MEASURES: Prevalence of
vitamin D deficiency and predictors of change in serum 25(OH)D. RESULTS: A total
of 2045 participants had serum 25(OH)D measured on two occasions (2000-2002 and
2007-2009) at a median interval of 7 years. Serum 25(OH)D decreased (42.7-39.4
nmol/L, P<.001) and the prevalence of vitamin D deficiency [25(OH)D <50 nmol/L]
increased significantly (60.6%-66.4%, P<.0001) despite vitamin D supplementation
increasing over the interval (7.2%-23.0%; P<.0001). In a multivariable model
adjusting for sex, race, BMI, age, season of blood draw, smoking and exercise, a
greater decline in serum 25(OH)D was noted in men compared with women (-8.0 vs
3.5 nmol/L, P<.0001), in participants of Hispanic ethnicity vs White and Black
ethnicity (P<.0001), in nonobese vs obese participants (-7.2 vs -4.0 nmol/L,
P=.005) and in nonusers vs users of vitamin D supplements (-5.7 vs -1.7 nmol/L,
P=.032). CONCLUSIONS: Despite increased vitamin D supplementation, serum 25(OH)D
decreased in an ethnically diverse cohort of Dallas County residents between 2000
2002 and 2007-2009. Features most predictive of a decline in serum 25(OH)D
include male sex, Hispanic ethnicity and weight gain.
PMID- 28502107
TI - A nano particle vector comprised of poly lactic-co-glycolic acid and
monophosphoryl lipid A and recombinant Mycobacterium avium subsp paratuberculosis
peptides stimulate a pro-immune profile in bovine macrophages.
AB - AIMS: We evaluated the potential of a nanoparticle (NP) delivery system to
improve methods of delivery of candidate peptide-based vaccines for
Paratuberculosis in cattle. METHODS AND RESULTS: Peptides derived from
Mycobacterium avium subsp. paratuberculosis (Map), and the pro-inflammatory
monophosphoryl lipid A (MPLA) were incorporated in polymeric NPs based on poly
(d,l-lactide-co-glycolide) (PLGA). The PLGA/MPLA NPs carriers were incubated with
macrophages to examine their effects on survival and function. PLGA/MPLA NPs,
with and without Map antigens, are efficiently phagocytized by macrophages with
no evidence of toxicity. PLGA/MPLA NP formulations did not alter the level of
expression of MHC I or II molecules. Expression of TNFalpha and IL12p40 was
increased in Map-loaded NPs. T-cell proliferation studies using a model peptide
from Anaplasma marginale demonstrated that a CD4 T-cell recall response could be
elicited with macrophages pulsed with the peptide encapsulated in the PLGA/MPLA
NP. CONCLUSIONS: These findings indicate PLGA/MPLA NPs can be used as a vehicle
for delivery and testing of candidate peptide-based vaccines. SIGNIFICANCE AND
IMPACT OF THE STUDY: These results will assist on more in depth studies on PLGA
NP delivery systems that may lead to the development of a peptide-based vaccine
for cattle.
PMID- 28502110
TI - A novel frameshift mutation of the ADAR1 gene in a Chinese patient with
dyschromatosis symmetrica hereditaria and the dermoscopic features.
PMID- 28502108
TI - Expression of the filaggrin gene in umbilical cord blood predicts eczema risk in
infancy: A birth cohort study.
AB - BACKGROUND: Filaggrin gene (FLG) expression, particularly in the skin, has been
linked to the development of the skin barrier and is associated with eczema risk.
However, knowledge as to whether FLG expression in umbilical cord blood (UCB) is
associated with eczema development and prediction is lacking. OBJECTIVE: This
study sought to assess whether FLG expression in UCB associates with and predicts
the development of eczema in infancy. METHODS: Infants enrolled in a birth cohort
study (n=94) were assessed for eczema at ages 3, 6, and 12 months. Five probes
measuring FLG transcripts expression in UCB were available from genomewide gene
expression profiling. FLG genetic variants R501X, 2282del4, and S3247X were
genotyped. Associations were assessed using Poisson regression with robust
variance estimation. Area under the curve (AUC), describing the
discriminatory/predictive performance of fitted models, was estimated from
logistic regression. RESULTS: Increased level of FLG expression measured by probe
A_24_P51322 was associated with reduced risk of eczema during the first year of
life (RR=0.60, 95% CI: 0.38-0.95). In contrast, increased level of FLG antisense
transcripts measured by probe A_21_P0014075 was associated with increased risk of
eczema (RR=2.02, 95% CI: 1.10-3.72). In prediction models including FLG
expression, FLG genetic variants, and sex, discrimination between children who
will and will not develop eczema at 3 months of age was high (AUC: 0.91, 95% CI:
0.84-0.98). CONCLUSIONS AND CLINICAL RELEVANCE: This study demonstrated, for the
first time, that FLG expression in UCB is associated with eczema development in
infancy. Moreover, our analysis provided prediction models that were capable of
discriminating, to a great extent, between those who will and will not develop
eczema in infancy. Therefore, early identification of infants at increased risk
of developing eczema is possible and such high-risk newborns may benefit from
early stratification and intervention.
PMID- 28502109
TI - Reproductive performance of resident and migrant males, females and pairs in a
partially migratory bird.
AB - Quantifying among-individual variation in life-history strategies, and associated
variation in reproductive performance and resulting demographic structure, is key
to understanding and predicting population dynamics and life-history evolution.
Partial migration, where populations comprise a mixture of resident and
seasonally migrant individuals, constitutes a dimension of life-history variation
that could be associated with substantial variation in reproductive performance.
However, such variation has rarely been quantified due to the challenge of
measuring reproduction and migration across a sufficient number of seasonally
mobile males and females. We used intensive winter (non-breeding season)
resightings of colour-ringed adult European shags (Phalacrocorax aristotelis)
from a known breeding colony to identify resident and migrant individuals. We
tested whether two aspects of annual reproductive performance, brood hatch date
and breeding success, differed between resident and migrant males, females and
breeding pairs observed across three consecutive winters and breeding seasons.
The sex ratios of observed resident and migrant shags did not significantly
differ from each other or from 1:1, suggesting that both sexes are partially
migratory and that migration was not sex-biased across surveyed areas. Individual
resident males and females hatched their broods 6 days earlier and fledged 0.2
more chicks per year than migrant males and females on average. Resident
individuals of both sexes therefore had higher breeding success than migrants.
Hatch date and breeding success also varied with a pair's joint migratory
strategy such that resident-resident pairs hatched their broods 12 days earlier
than migrant-migrant pairs, and fledged 0.7 more chicks per year on average.
However, there was no evidence of assortative pairing with respect to migratory
strategy: observed frequencies of migrant-migrant and resident-resident pairs did
not differ from those expected given random pairing. These data demonstrate
substantial variation in two key aspects of reproductive performance associated
with the migratory strategies of males, females and breeding pairs within a
partially migratory population. These patterns could reflect direct and/or
indirect mechanisms, but imply that individual variation in migratory strategy
and variation in pairing among residents and migrants could influence selection
on migration and drive complex population and evolutionary dynamics.
PMID- 28502111
TI - Upregulation of ASAP3 contributes to colorectal carcinogenesis and indicates poor
survival outcome.
AB - The function and clinical implication of ArfGAP with SH3 domain, ankyrin repeat,
and PH domain 3 (ASAP3) in colorectal cancer (CRC) remains undefined. In the
present study, we showed that the expression level of ASAP3 was dramatically
increased in CRC and its upregulation was associated with American Joint
Committee on Cancer stage (P < 0.001) and poor prognosis (P = 0.0022). The
combination of stage and ASAP3 expression improved the prediction of survival in
CRC patients. Suppression of ASAP3 inhibited cell proliferation by inducing G1
phase arrest without influencing apoptosis. ASAP3 promoted growth of colon tumors
in mice with colitis, and accelerated cell invasion and migration in vitro.
Increased ASAP3 was associated with activation of the nuclear factor-kappaB (NF
kappaB) canonical pathway in CRC. Upregulation of ASAP3 increased the
phosphorylation and nuclear translocation of the p65 NF-kappaB subunit.
Mechanistically, ASAP3 interacts with NF-kappaB essential modulator (NEMO) and
could reduce the polyubiquitinylation of NEMO. Overall, ASAP3 might regulate NF
kappaB via binding to NEMO. ASAP3 acts as an oncogene in colonic cancer and could
be a potential biomarker of colon carcinogenesis.
PMID- 28502112
TI - Sodium-glucose cotransporter-2 inhibitor luseogliflozin added to glucagon-like
peptide 1 receptor agonist liraglutide improves glycemic control with bodyweight
and fat mass reductions in Japanese patients with type 2 diabetes: A 52-week,
open-label, single-arm study.
AB - AIMS/INTRODUCTION: The aim of the present study was to evaluate the safety and
efficacy of luseogliflozin added to liraglutide monotherapy in Japanese
individuals with type 2 diabetes. MATERIALS AND METHODS: This 52-week,
multicenter, open-label, single-arm clinical study enrolled Japanese patients who
had inadequate glycemic control with diet/exercise and liraglutide monotherapy.
Major efficacy end-points included the changes from baseline in glycated
hemoglobin, fasting plasma glucose and bodyweight. Body composition was also
assessed in individuals who had access to bioelectrical impedance analysis.
Safety assessments included adverse events, clinical laboratory tests, vital
signs and 12-lead electrocardiograms. RESULTS: Of 76 patients who received
luseogliflozin, 62 completed the study. The changes from baseline in glycated
hemoglobin, fasting plasma glucose, and bodyweight (mean +/- SE) were -0.68 +/-
0.10%, -32.1 +/- 3.6 mg/dL and -2.71 +/- 0.24 kg at week 52, respectively (all, P
< 0.001 vs baseline). Luseogliflozin was associated with greater reductions in
fat mass than lean mass at all measuring points (n = 22): fat vs lean mass
changes (mean +/- SE) at week 52 were -2.49 +/- 0.45 kg (P < 0.001 vs baseline)
and -0.44 +/- 0.26 kg (P = 0.107 vs baseline), respectively. Insulin secretion
and Matsuda Index were also improved at weeks 12 and 52 compared with baseline.
Adverse events and adverse drug reactions occurred in 65.8 and 27.6% of patients,
respectively. The overall safety profile, including frequency of hypoglycemia,
was found to be consistent with those of previous studies and there were no new
safety concerns. CONCLUSIONS: Luseogliflozin added to liraglutide was well
tolerated, and improved glycemic control with bodyweight and fat mass reductions
in Japanese type 2 diabetes patients.
PMID- 28502114
TI - Risk factors for executive function difficulties in preschool and early school
age preterm children.
AB - AIM: To investigate the relationship between executive functioning and social and
perinatal risk factors in four- to five-year-old preterm children. METHODS: Using
standardised measures of general intelligence and performance-based executive
function (EF) tests prior to starting kindergarten, 141 children born preterm
(<33 weeks of gestation) and 77 term comparison children were assessed. Parental
and teacher reports of executive functioning were completed when the children
commenced kindergarten. The preterm and the term comparison groups were compared
on measures of intelligence and EFs using independent-groups t-tests, and
multivariate regression analyses were performed to identify factors predictive of
intelligence and executive functioning in the preterm group. RESULTS: The preterm
group performed significantly more poorly than the comparison group on all
intelligence and EF tests. The parental reports of the preterm and term
comparison children's EF did not differ significantly, but the teachers reported
elevated EF difficulties for the preterm group. Higher social risk, in particular
lower educational level of the main caregiver, was the strongest predictor for
the preterm children's intelligence and EF results. CONCLUSION: Social risk
factors are strongly associated with impaired early EF outcomes in preterm
children.
PMID- 28502116
TI - Phenolic Composition, Anti-Inflammatory, Antioxidant, and Antimicrobial
Activities of Alchemilla mollis (Buser) Rothm.
AB - The current study was designed to evaluate the antioxidant, anti-inflammatory and
antimicrobial activities of Alchemilla mollis (Buser) Rothm. (Rosaceae) aerial
parts extracts. Chemical composition was analyzed by spectrophotometric and
chromatographic (HPLC) techniques. The antioxidant properties assessed included
DPPH. and ABTS.+ radical scavenging, beta-carotene-linoleic acid co-oxidation
assay. Antimicrobial activity was evaluated with disc diffusion and micro
dilution method. In order to evaluate toxicity of the extracts, with the
sulforhodamine B colorimetric assay L929 cell line (mouse fibroblast) was used.
The anti-inflammatory activities of the potent antioxidant extracts (methanol,
70% methanol, and water extracts) were determined by measuring the inhibitory
effects on NO production and pro-inflammatory cytokine TNF-alpha levels in
lipopolysaccharide stimulated RAW 264.7 cells. 70% methanol and water extracts
which were found to be rich in phenolic compounds (184.79 and 172.60 mg GAE/g
extract) showed higher antioxidant activity. Luteolin-7-O-glucoside was the main
compound in the extracts. Ethyl acetate and 70% methanol extracts showed higher
antibacterial activity against Staphylococcus aureus and Salmonella enteritidis
with MIC value of 125 MUg/ml. 70% methanol extract potentially inhibited the NO
and TNF-alpha production (18.43 MUm and 1556.22 pg/ml, respectively, 6 h).
PMID- 28502115
TI - Use of the 10-Group Classification System to analyze how the population control
policy change in China has affected cesarean delivery.
AB - OBJECTIVE: To analyze the initial effect following the relaxation of China's
population control policy on the cesarean delivery (CD) rate using the 10-Group
Classification System (TGCS). METHODS: A retrospective study included all
deliveries at a center in Nanjing, China, during 2014-2015. The deliveries were
classified using the TGCS. The obstetric populations and the CD rates in each
group were compared between 2014 and 2015. RESULTS: Overall, 11 006 deliveries
were analyzed. The overall CD rate increased from 28.3% (1623/5737) in 2014 to
33.8% (1782/5269) in 2015 (P<0.001). The largest contributor to the overall CD
rate-accounting for approximately one-third of all CDs-were nulliparous women
with a single cephalic term pregnancy and induced labor or prelabor CD (group 2);
the CD rate in this group increased from 27.2% to 31.4%. Moreover, the proportion
of women with a single cephalic term pregnancy with previous CD (group 5) steeply
increased from 6.4% to 10.4% of all deliveries; the CD rate in this group during
2014-2015 was 76.6%. CONCLUSION: With China ending its one-child policy, the
characteristics of the obstetric population changed. Women with a single cephalic
term pregnancy with previous CD were the largest contributor to the CD rate
increase.
PMID- 28502117
TI - Passive Membrane Penetration of the Serotonin Precursor 5-Hydroxytryptophan is
Controlled by Its Zwitterion.
AB - Species-specific partition coefficients in the octanol/water system were
determined for the neurotransmitter serotonin (5-HT) and its precursor 5
hydroxytryptophan (5-HTP). The pH-independent partition coefficients (p) of the
individual microspecies were determined by combination of experimentally measured
distribution constants and a custom-tailored evaluation method, using highly
similar auxiliary compounds. Experimental microscopic partition coefficients for
triprotic molecules have only been reported before for thyroxine and its
derivatives. The parabolic pH-distribution profile of 5-HT shows the dominance of
the lipophilic non-charged microspecies, with a log p of 0.66. However, the most
lipophilic non-charged form of 5-HTP, with a log p of 0.31, has no significant
contribution to the distribution coefficient at any pH value. Instead, the less
lipophilic zwitterionic protonation isomer dominates the distribution in the pH
range 2.10 - 11.11. Although the non-charged microspecies of 5-HTP is 151 times
more lipophilic than its zwitterionic protonation isomer, the overwhelming
dominance of the zwitterionic form ensures that its contribution to the overall
lipophilicity exceeds 1320 times that of the non-charged one. This fact is
another counter-example of the widespread belief that passive diffusion into
lipophilic media is predominated by the non-charged species. The lipophilicity
profile of 5-HT and 5-HTP is depicted in terms of species-specific
lipophilicities.
PMID- 28502113
TI - Epigenetic modifications of the VH region after DJH recombination in Pro-B cells.
AB - The variable region of murine immunoglobulin heavy chain (Igh) is assembled by
sequential DH -JH and VH -DJH recombination. The accessibility of the Igh locus
determines the order of rearrangement. Because of the large number of VH genes
and the lack of a suitable model, the epigenetic modifications of VH genes after
DJH recombination have not previously been characterized. Here, we employed two v
Abl pro-B cell lines, in which the Igh locus is in germline and DJH -recombined
configurations, respectively. The DJH junction displays the characteristics of a
recombination centre, such as high levels of activation-associated histone
modifications and recombination-activating gene protein (RAG) binding in DJH
rearranged pro-B cells, which extend the recombination centre model proposed for
the germline Igh locus. The different domains of the VH region have distinct
epigenetic characteristics after DJH recombination. Distal VH genes have higher
levels of active histone modifications, germline transcription and Pax5 binding,
and good quality recombination signal sequences. Proximal VH genes are relatively
close to the DJH recombination centre, which partially compensates for the low
levels of the above active epigenetic modifications. DJH recombination centre
might serve as a cis-acting element to regulate the accessibility of the VH
region. Furthermore, we demonstrate that RAG weakly binds to functional VH genes,
which is the first detailed assessment of RAG dynamic binding to VH genes. We
provide a way for VH -DJH recombination in which the VH gene is brought into
close proximity with the DJH recombination centre for RAG binding by a Pax5
dependent chromosomal compaction event, and held in this position for subsequent
cleavage and VH -DJH joining.
PMID- 28502119
TI - Neutrophil-to-lymphocyte ratio decreases after treatment of psoriasis with
therapeutic antibodies.
PMID- 28502118
TI - The role of rare morph advantage and conspicuousness in the stable gold-dark
colour polymorphism of a crater lake Midas cichlid fish.
AB - Genetically based stable colour polymorphisms provide a unique opportunity to
study the evolutionary processes that preserve genetic variability in the wild.
Different mechanisms are proposed to promote the stability of polymorphisms, but
only few empirical examples have been documented, resulting in an incomplete
understanding of these mechanisms. A remarkable genetically determined stable
colour polymorphism is found in the Nicaraguan Midas cichlid species complex
(Amphilophus cf. citrinellus). All Midas cichlids start their life with a dark
grey coloration (dark morph), but individuals carrying the dominant "gold" allele
(c. 10%) lose their melanophores later in life, revealing the underlying orange
coloration (gold morph). How this polymorphism is maintained remains unclear. Two
main hypotheses have been proposed, both suggesting differential predation upon
colour morphs as the proximate mechanism. One predicts that the conspicuous gold
morph is more likely to be preyed upon, but this disadvantage is balanced by
their competitive dominance over the dark morph. The second hypothesis suggests a
rare morph advantage where the rarer gold morph experiences less predation.
Empirical evidence for either of these mechanisms is still circumstantial and
inconclusive. We conducted two field experiments in a Nicaraguan crater lake
using wax models simulating both morphs to determine predation pressure upon
Midas cichlid colour morphs. First, we tested the interaction of coloration and
depth on attack rate. Second, we tested the interaction of fish size and
coloration. We contrasted the pattern of attacks from these experiments to the
predicted predation patterns from the hypotheses proposed to explain the colour
polymorphism's stability. Large models imitating colour morphs were attacked at
similar rates irrespectively of their position in the water column. Yet, attacks
upon small models resembling juveniles were directed mainly towards dark models.
This resulted in a significant size-by-colour interaction. We suggest that gold
Midas cichlids experience a rare morph advantage as juveniles when individuals of
this morph are extremely uncommon. But this effect is reduced or disappears among
adults, where gold individuals are relatively more common. Thus, the interaction
of rare morph advantage and conspicuousness, rather than either of those factors
alone, is a likely mechanism resulting in the stability of the colour
polymorphism in Midas cichlids.
PMID- 28502120
TI - Gut microbial communities of American pikas (Ochotona princeps): Evidence for
phylosymbiosis and adaptations to novel diets.
AB - Gut microbial communities provide many physiological functions to their hosts,
especially in herbivorous animals. We still lack an understanding of how these
microbial communities are structured across hosts in nature, especially within a
given host species. Studies on laboratory mice have demonstrated that host
genetics can influence microbial community structure, but that diet can overwhelm
these genetic effects. We aimed to test these ideas in a natural system, the
American pika (Ochotona princeps). First, pikas are high-elevation specialists
with significant population structure across various mountain ranges in the USA,
allowing us to investigate whether similarities in microbial communities match
host genetic differences. Additionally, pikas are herbivorous, with some
populations exhibiting remarkable dietary plasticity and consuming high levels of
moss, which is exceptionally high in fibre and low in protein. This allows us to
investigate adaptations to an herbivorous diet, as well as to the especially
challenging diet of moss. Here, we inventoried the microbial communities of pika
caecal pellets from various populations using 16S rRNA sequencing to investigate
structuring of microbial communities across various populations with different
natural diets. Microbial communities varied significantly across populations, and
differences in microbial community structure were congruent with genetic
differences in host population structure, a pattern known as "phylosymbiosis."
Several microbial members (Ruminococcus, Prevotella, Oxalobacter and Coprococcus)
were detected across all samples, and thus likely represent a "core microbiome."
These genera are known to perform a number of services for herbivorous hosts such
as fibre fermentation and the degradation of plant defensive compounds, and thus
are likely important for herbivory in pikas. Moreover, pikas that feed on moss
harboured microbial communities highly enriched in Melainabacteria. This
uncultivable candidate phylum has been proposed to ferment fibre for herbivores,
and thus may contribute to the ability of some pika populations to consume high
amounts of moss. These findings demonstrate that both host genetics and diet can
influence the microbial communities of the American pika. These animals may be
novel sources of fibre-degrading microbes. Last, we discuss the implications of
population-specific microbial communities for conservation efforts in this
species.
PMID- 28502121
TI - Merkel cell carcinoma: morphologic aspects on reflectance confocal microscopy.
PMID- 28502124
TI - Poster Presentations.
PMID- 28502126
TI - Program Summary.
PMID- 28502123
TI - Novel method for the depletion of cariogenic bacteria using dextranomer
microspheres.
AB - Streptococcus mutans is recognized as one of the key contributors to the
dysbiotic state that results in dental caries. Existing treatment strategies
reduce the incidence of tooth decay, but they also eliminate both the cariogenic
and beneficial microbes. Here we introduce a novel treatment alternative using
Sephadex, cross-linked dextranomer microspheres (DMs), typically used for gel
filtration chromatography. In addition DM beads can be used for affinity
purification of glucosyltransferases (GTFs) from S. mutans. In this study we take
advantage of the native pathogenic mechanisms used by S. mutans to adhere, form a
biofilm and induce dental caries through the expression of surface-associated
GTFs. We demonstrate that planktonic and biofilm-grown (adhered to hydroxyapatite
coated pegs to mimic the tooth surface) S. mutans, specifically and competitively
attach to DMs. Further investigation demonstrated that DMs are a specific
affinity resin for S. mutans and other cariogenic/pathogenic oral streptococci,
whereas other commensal and probiotic strains failed to readily adhere to DMs.
Using antimicrobial cargo loaded into the DM lumen, we demonstrate that when in
co-culture with non-binding to even modestly binding commensal species, S. mutans
was selectively killed. This proof of concept study introduces a novel means to
safely and effectively reduce the pool of S. mutans and other pathogenic
streptococci in the oral cavity with limited disturbance of the necessary
commensal (healthy) microbiota when compared with current oral healthcare
products.
PMID- 28502122
TI - Humanized NOG mice as a model for tuberculosis vaccine-induced immunity: a
comparative analysis with the mouse and guinea pig models of tuberculosis.
AB - The humanized mouse model has been developed as a model to identify and
characterize human immune responses to human pathogens and has been used to
better identify vaccine candidates. In the current studies, the humanized mouse
was used to determine the ability of a vaccine to affect the immune response to
infection with Mycobacterium tuberculosis. Both human CD4+ and CD8+ T cells
responded to infection in humanized mice as a result of infection. In humanized
mice vaccinated with either BCG or with CpG-C, a liposome-based formulation
containing the M. tuberculosis antigen ESAT-6, both CD4 and CD8 T cells secreted
cytokines that are known to be required for induction of protective immunity. In
comparison to the C57BL/6 mouse model and Hartley guinea pig model of
tuberculosis, data obtained from humanized mice complemented the data observed in
the former models and provided further evidence that a vaccine can induce a human
T-cell response. Humanized mice provide a crucial pre-clinical platform for
evaluating human T-cell immune responses in vaccine development against M.
tuberculosis.
PMID- 28502129
TI - Diagnostic Role of RASSF1A and p16INK4a Promoter Gene Hypermethylation in Serum
DNA of Lung Cancer Patients: Clinicopathological Significance.
AB - The most common inactivation mechanism of tumor suppressor genes, RASSF1A and
p16INK4a, in lung cancer is hypermethylation. We detected the methylation status
of RASSF1A and p16INK4a in serum of lung cancer patients using methylation
specific PCR and analyzed their clinicopathological significance. Each of RASSF1A
and p16INK4a hypermethylation was detected in 31.1% cancer patients but not in
benign lung lesion patients. Hypermethylation was preferentially observed in
small cell lung cancer (SCLC) for RASSF1A (50%), but not for p16INK4a. In non
small cell lung cancer (NSCLC), RASSF1A and p16INK4a hypermethylation were found
in 27% and 37.8% respectively. Hypermethylation of RASSF1A was not correlated
with clinicopathological character. While, p16INK4a hypermethylation was
associated with age >60 years, smoking and squamous cell carcinoma (SCC) (P =
0.033), but not with gender and pathological stages of NSCLC. Sensitivity and
specificity of each gene were 31.1% and 100% respectively and the sensitivity
improved with evaluation of a combination of the two genes (55.6%). These
findings suggest that serum RASSF1A and p16INK4a hypermethylation are promising
diagnostic method for detection of lung cancer. As regard the clinicopathological
characteristics, p16INK4a hypermethylation may provide a more specific approach
than RASSF1A hypermethylation.
PMID- 28502130
TI - Diagnostic and Prognostic Values of Monocyte Chemotactic Protein-1 in Ascitic
Fluid of Patients with Spontaneous Bacterial Peritonitis.
AB - Spontaneous bacterial peritonitis (SBP) is a severe complication in cirrhotics
with ascites. Monocyte chemotactic protien-1 (MCP-1) is a chemotactic factor for
monocytes/macrophages, and it activates lymphocytes and neutrophils during
infection. This study aimed to evaluate the role of MPC-1 in the pathogenesis of
SBP and assess its prognostic value and correlation to disease severity. The
study included ninety patients with liver cirrhosis and ascites. Patients were
divided into 2 groups: Group I including 45 ascetic patients with SBP (polymorph
nuclear cell count (PMN) >= 250 cell/mm3 in ascitic fluid), and Group II
including 45 ascetic patients without SBP. Assessment of the severity of liver
cirrhosis was done using the modified Child-Pugh and model for end stage liver
disease (MELD) scores. Ascetic fluid samples were subjected to total leucocytic
count and differential, albumin, protein, glucose, and serum-ascetic albumin
gradient analysis Ascetic fluid levels of (MCP-1was measured by ELISA. Higher
level was detected in patients with SBP as compared to those without SBP. The
number of polymorph nuclear cell count (PMN) >= 250 cell/mm3 in ascitic fluid)
was used as gold standard for diagnosis of SBP. The diagnosis sensitivity and
specificity of MCP level test were 86.7% and 95.4% respectively at cutoff
of122.5ng/ml with accuracy 91%. MCP-1 level showed positive significant
correlation with TLC, PMN leucocytes and MELD score. In conclusion, ascitic fluid
MCP-1 level could be a reliable test for diagnosis of SBP, and could be used as a
prognostic marker due to its positive correlation with the severity of liver
disease.
PMID- 28502128
TI - Belatacept-Resistant Rejection Is Associated With CD28+ Memory CD8 T Cells.
AB - Recently, newer therapies have been designed to more specifically target
rejection in an effort to improve efficacy and limit unwanted toxicity.
Belatacept, a CD28-CD80/86 specific reagent, is associated with superior patient
survival and graft function compared with traditional therapy, but its adoption
as a mainstay immunosuppressive therapy has been tempered by increased rejection
rates. It is essential that the underlying mechanisms associated with this
rejection be elucidated before belatacept is more widely used. To that end, we
designed a study in a nonhuman primate kidney transplant model where animals were
treated with either a belatacept- or a tacrolimus-based immunosuppressive
regimen. Interestingly, we found that elevated pretransplant frequencies of CD28+
CD8+ TEMRA cells are associated with rejection on belatacept but not tacrolimus
treatment. Further analysis showed that the CD28+ CD8+ TEMRA cells rapidly lose
CD28 expression after transplant in those animals that go on to reject with the
allograft infiltrate being predominantly CD28- . These data suggest that CD28+
memory T cells may be resistant to belatacept, capable of further differentiation
including loss of CD28 expression while maintaining effector function. The unique
signaling requirements of CD28+ memory T cells provide opportunities for the
development of targeted therapies, which may synergize with belatacept to prevent
costimulation-independent rejection.
PMID- 28502131
TI - Diagnostic Value of Presepsin in Neonatal Sepsis.
AB - Presepsin has recently been described as biomarker of sepsis. The aim of this
study was to investigate the diagnostic accuracy of presepsin in diagnosing
neonatal sepsis and discriminating sepsis from non-infectious systemic
inflammatory response syndrome (SIRS). The study included 70 full term neonates
divided into three groups: 1) Sepsis group (22 patients with clinically suspected
sepsis and positive blood cultures) 2) Non-infectious SIRS group (28 patients
with clinically suspected sepsis and persistently negative blood cultures) 3)
Control group (20 healthy neonates without any clinical signs of infection).
Plasma presepsin level was measured by chemiluminescent enzyme immunoassay
(CLEIA) and results were compared with that of C-reactive protein (CRP) assay.
The results revealed that presepsin levels were significantly higher in sepsis
group than in non-infectious SIRS group and controls (P <0.001). The area under
the receiver operating characteristics (ROC) curve (AUC) for discriminating
sepsis from non-infectious SIRS patients was 0.990 for presepsin and it was
significantly higher than that of CRP (0.804). The best cut-off value for
presepsin was 812 pg/ml, which was associated with sensitivity, specificity and
negative predictive value of 95.5%, 91.7% and 97.8% respectively. In conclusion,
presepsin is a sensitive and accurate biomarker and is useful for the diagnosis
of sepsis and discrimination from non-infectious SIRS in neonates.
PMID- 28502132
TI - Evaluation of Non Invasive versus Invasive Methods for Diagnosis of Helicobacter
pylori Infection among Patients with Gastroduodenal Disorders.
AB - H. pylori, a spiral gram-negative bacterium, is associated with gastroduodenal
diseases. All H. pylori diagnostic assays have limitations. Cytotoxin-associated
gene A (cag A), a virulence marker, can be identified by PCR. We evaluated H.
pylori diagnostic methods, invasive: rapid urease test (RUT), and
histopathological examination (HE), and serology as non-invasive method. Positive
cases were studied for presence of cag A gene. Upper endoscopies and gastric
biopsies were performed on 67 dyspeptic patients for RUT, HE and PCR. Anti H.
pyloriIgG were measured by ELISA. Of 67 dyspeptic patients, 23 (34%) had more
than one endoscopic finding, 46 (68.7%) were H.pylori positive by HE, and
21(31.3%) were negative with variable grades of mucosal antral neutrophil
infiltration. Of the 46 HE positives, PCR detected CagA in 22 (47.8%). Using HE
as the gold standard test, the sensitivity of ELISA and RUT was 93.48% and
86.96%, respectively; and the specificity was 85.71% and 47.62%, respectively. In
conclusion, IgG detection by ELISA is a suitable screening test for diagnosis of
H. pylori associated gastroduodenal diseases. Histopathology should be performed
in ELISA negative cases to exclude infection.
PMID- 28502133
TI - T Regulatory Cells Response to Allergen Specific Immunotherapy in Patients with
Allergic Airway Diseases: A Prospective Study.
AB - Forkhead box P3 (FoxP3) T regulatory (Treg) cells modulate the immune system by
blocking other types of T-cells. They maintain tolerance to self-antigens and
help in inducing tolerance to foreign antigens. A deregulation of FoxP3 Tregs
seems to play an important role in allergic disorders. The aim of this work was
to study the response of FoxP3 Treg cells and their FoxP3 expression in patients,
attending the Allergy Unit and the Chest Outpatient Clinic, Faculty of Medicine,
Zagazig University, with allergic airway diseases, before and 1 year after
receiving subcutaneous allergen specific immunotherapy (SIT). This prospective
study was carried out on 25 patients with allergic airway diseases, confirmed by
positive skin test, and that showed clinical improvement one year after SIT. All
cases were subjected to total immunoglobulin E quantitation by ELISA. FoxP3 Treg
cells frequency and FoxP3 relative fluorescence intensity, as an indicator of
Tregs function, were assessed by flowcytometry. The results were compared before
and after SIT. Twenty five age and sex matched apparently healthy volunteers were
enrolled as controls. Our findings demonstrated that in comparison to the control
group, the count of FoxP3 T regulatory cells was higher; however, the function
was lower among the enrolled patients (P= 0.007 and P< 0.001, respectively). When
FoxP3 Tregs were compared in the patients before and one year after SIT, it was
found that both the count and FoxP3 expression showed statistically significant
increase (P< 0.001). An inverse correlation was found between FoxP3 Tregs count
and FoxP3 expression. It is concluded that patients with allergic airway diseases
have increased number of FoxP3 Treg cells but with defective function. SIT plays
a role in increasing the number of FoxP3 Tregs and improving their suppressive
function, which leads to control of airway inflammation and thus clinical
improvement.
PMID- 28502134
TI - Thyroid Dysfunctions in a Sample of Egyptian Children and Adolescents with
Systemic Lupus Erythematosus: Relation to Disease Activity and Duration.
AB - Systemic lupus erythematosus (SLE) is a chronic, autoimmune, inflammatory disease
affects any organ of the body, including the thyroid gland. Both hypothyroidism
and hyperthyroidism have been found in SLE patients more frequently than general
population. The aim of this study was to evaluate the frequency of autoimmune
thyroid dysfunctions in juvenile SLE and its relation to disease activity and
duration. A prospective case-control study was carried on 40 children with
juvenile SLE and 30 healthy as controls, all were subjected to measurement of
serum TSH, Free T3, Free T4 and anti-TG by ELISA. The SLEDAI scoring system was
used to evaluate the disease activity. Fourteen patients (35%) demonstrated
thyroid dysfunctions, in the form of; euthyroid sick syndrome in 6 (15%), overt
hypothyroidism in 4 (10%), hyperthyroidism in 2 (5%) and subclinical
hyperthyroidism in 2 cases (5%). Positive anti-TG was detected in 8 cases (20%)
with a significant (P<0.05) increase in mean levels of serum anti-thyroglobulin
antibodies in patients (38.25+/-15.224 Iu/ml) as compared to controls (22.79+/
3.71 Iu/ml). There was a significant positive correlation between SLEDAI and anti
TG and a significant negative correlation between disease duration and anti-TG,
TSH In conclusion; thyroid dysfunctions increase in children with SLE patients
and correlate with severity of the disease.
PMID- 28502135
TI - Systemic Lupus Erythmatosus is Associated with Disturbed Cytokine Milieu and
Increased TNF-Related Apoptosis-Induced Ligand Levels.
AB - Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is
cytotoxic to a wide variety of transformed cells, but not to most normal cells.
This study measures serum levels of tumor necrosis factor (TNF)-alpha,
interleukin (IL)-6 and 10 and soluble TRAIL (sTRAIL) in patients with SLE and
assesses their relation to severity of the disease. The study included 70 SLE
patients and 20 healthy controls. Patients were diagnosed according to criteria
proposed by the American Rheumatism Association for classification of SLE and
disease activity was scored using the British Isles Lupus Assessment Group (BILAG
2004). All study participants were subjected to estimation of TNF-alpha, IL-6, IL
10 and sTRAIL using ELISA. Results revealed that mean disease duration was 6.5+/
1.5 years, mean BILAG score was 18.2+/-12.1, while 15 patients (21.4%) had
quiescent disease. Blood levels of C3 and C4 and leucocytic count showed
progressive decrease, while serum C-reactive protein and anti-double strand DNA
antibodies levels showed marked increase with increased disease activity. Five
patients (7.1%) were neutropenic. Serum levels of sTRAIL and IL-6 were
significantly (P>0.05) higher in patients (1113.5+/-294 ng/ml and 60+/-21.5
ng/ml, respectively) than controls (354.7+/-47.2 ng/ml and 15.6+/-3.3 ng/ml,
respectively) and in patients had active (1157+/-317 ng/ml and 64.3+/-20.7 ng/ml,
respectively) versus patients had quiescent disease (965.4+/-115 ng/ml and 45.4+/
18 ng/ml, respectively). Serum levels of TNF-alpha were significantly (P>0.05)
higher in patients (2.4+/-0.7 ng/ml) especially those with active (2.8+/-2 ng/ml)
disease compared to controls (1.45+/-0.9 ng/ml). Patients with quiescent disease
showed non-significantly higher TNF-alpha level (1.52+/-0.5 ng/ml) as compared to
control, but significantly lower than patients with active disease. Serum levels
of IL-10 were significantly lower in total patients (2.4+/-0.7 ng/ml) and
patients with active disease (2.33+/-0.7) as compared to control (2.61+/-0.6
ng/ml) with a non-significantly (P>0.05) higher levels in patients with quiescent
disease (2.61+/-0.6 ng/ml) than patients with active disease. Estimated serum
sTRAIL, TNF-alpha and IL-6 levels showed positive significant correlation with
calculated BILAG activity score, while estimated serum IL-10 levels showed
negative significant correlation with activity score. In conclusion, SLE is
associated with disturbed levels of serum cytokines and sTRAIL. These
disturbances may underlie pathogenesis and/or activation of SLE as BILAG-2004
numeric scoring system significantly correlated with estimated levels of serum
cytokines and sTRAIL.
PMID- 28502136
TI - CD4+ CD25+ CD127low Regulatory T Cells as Indicator of Rheumatoid Arthritis
Disease Activity.
AB - Rheumatoid arthritis (RA) is an autoimmune disease characterized by disturbed
immune regulation, inducing a progressive cartilage and bone destruction. Despite
enrichment of T regulatory cell (T-regs) in synovial fluid, conflicting results
are reported concerning T-regs in peripheral blood (PB) of RA patients. To
determine possible correlation between the frequency of PB CD4+ CD25+CD127low (T
regs) with RA disease activity. Forty females with RA, classified according to
the Disease Activity Score 28 (DAS-28), as highly active, mild-moderate or low
disease activity; and 20 age and sex matched healthy controls, were enrolled to
study CD4+ CD25+ CD127low T- regs in PB by flow cytometry. Active RA patients had
lower frequency of the CD4+ CD25+ CD127low T- regs compared to those with mild
moderate or low disease activity (P <0.001). The frequencies of the T- regs
showed negative correlation with the DAS-28 (P<0.01). In conclusion, CD4+ CD25+
CD127low T-regs is significantly lower in highly active RA patients compared to
patients with lower activity or controls.
PMID- 28502137
TI - Angiopoietin-2 as A Biomarker For Echocardiographic Abnormalities and Carotid
Atherosclerosis In Rheumatoid Arthritis Patients.
AB - Atherosclerosis and cardiovascular diseases (CVD) are increasingly recognised
complications of rheumatoid arthritis (RA). Angiopoietin 2 (Ang-2) levels have
been associated with clinically overt CVD in general population; we assessed
serum Ang-2 levels and its correlation with Echocardiographic abnormalities and
carotid intima-media thickness in RA patients. 44 RA patients without clinically
overt CVD and 44 healthy controls were assessed by questionnaire and clinical
examination. Disease activity score (DAS-28) was calculated. Laboratory
investigations included measurement of serum Ang-2, Rheumatoid factor (RF), anti
cyclic citrullinated peptide (Anti-CCP), and C reactive protein (CRP). Doppler
Echocardiography and Carotid ultrasonography were done to all patients and
controls. Mean age of RA patients was 44.4+/-9.6 and about (86.4%) 38 were
females. Mean levels of Ang-2 was higher in RA patients (17.591+/-13.9 ng/ml) as
compared to controls (7.909 +/-4.10 ng/ml) P<0.001 and was significantly elevated
in RA patients with left ventricular (LV) diastolic dysfunction (23.53+/-7.75
ng/ml) than those without dysfunction (14.81+/-15.33ng/ml), P<0.05 and was
significantly elevated in RA patients with carotid intima-media thickness (cITM)
>0.6mm (21.12+/-14.79 ng/ml), P<0.005. Serum Ang-2 correlated positively with
disease duration, DAS-28, LV posterior wall thickness, E wave velocity and cIMT.
In conclusion, serum Ang-2 level is associated with LV diastolic dysfunction and
increased carotid intima-media thickness in RA patients and may be useful
biomarker for subclinical CVD and atherosclerosis in RA patients.
PMID- 28502138
TI - Presepsin a Diagnostic Marker for Sepsis in Intensive Care Unit Patients.
AB - The aim of the study was to evaluate the usefulness of presepsin as a diagnostic
marker of sepsis in intensive care unit (ICU) patients. Presepsin was measured by
a rapid method based on a chemiluminescent enzyme immunoassay (PATHFAST). The
clinical usefulness of presepsin to diagnose sepsis and septic shock was studied
and compared with procalcitonin, C-reactive protein and total leucocytic count.
This study was conducted on 53 individuals divided into 3 groups. Group I
included 28 adult ICU patients with at least two diagnostic criteria for systemic
inflammatory response syndrome (SIRS) as patient group, Group IIa 15 patients
admitted to ICU for any medical cause but with no evidence of infection were
enrolled as patient control group and further 10 apparently healthy subjects as
healthy control group. Patients were further subdivided retrospectively according
to the final diagnosis into: patients with sepsis 16 (57.1%) and septic shock 12
(42.9%), from which 17 (59.3%) improved while 11(39.3%) did not survive. The
presepsin values were significantly higher in patients with sepsis than the
control groups. The area under ROC curve (AUC) for discriminating sepsis from non
septic conditions for presepsin was greater than the AUC of PCT, CRP or TLC. This
suggests that presepsin has high specificity and sensitivity for sepsis
diagnosis. In conclusion, presepsin can be used as a useful biomarker for the
diagnosis of sepsis. It is readily available, cost-effective and able to
distinguish septic patients in a complex population.
PMID- 28502139
TI - Serum Interleukin-33 in Behcet's Disease: Its Relation to Disease Activity and
Clinical Manifestations.
AB - : Behcet's disease (BD) is a chronic systemic inflammatory disorder characterized
by a course of remissions and exacerbations of unpredictable frequency and
duration. Pro-inflammatory cytokines seem to be responsible for the enhanced
inflammatory response in BD. AIM OF THE WORK: This study aimed to investigate
serum levels of IL-33 in patients with Behcet's disease (BD) and their
relationship to disease activity and clinical manifestations. Thirty patients
with BD were enrolled and subjected to assessment of disease activity according
to Behcet's Disease Current Activity Form (BDCAF) score. Serum IL-33 levels were
determined using Enzyme-Linked-Immunosorbent Assay (ELISA). Thirty age and sex
matched rheumatoid arthritis patients and thirty healthy volunteers were included
in this study as control groups. Serum IL-33 level was 132.5+/-19 pg?ml, 101.2+/
20.1 pg?ml and 31.5+/-10.5 pg?ml in RA, BD and healthy control groups
respectively. IL-33 was significantly higher in BD patients (101.2+/-20.1pg/ml)
as compared to healthy controls (31.5+/-10.5 pg/ml) but lower than rheumatoid
arthritis patients (132.5+/-19.1 pg/ml). Levels of IL-33 were significantly
increased in BD patients with skin lesions (Erythema nodosum & Acneiform lesions)
and ocular lesions (retinal vasculitis) (P<0.05), and a positive correlation was
found between BDCAF score and IL-33serum levels (r=0.9, P<0.001). In conclusions,
serum IL-33 level is elevated in active BD patients with skin and ocular
affection and correlates with disease activity.
PMID- 28502140
TI - Expression of IL-23 mRNA in Systemic Lupus Erythramtosus Patients: Relation with
Disease Activity.
AB - Systemic lupus erythematosus (SLE) is a multisystem autoimmune connective tissue
disorder characterized by loss of self-tolerance causing immune-mediated tissue
destruction and various clinical presentations. Cytokine-mediated immunity
involved in the pathogenesis of SLE. Recently, IL-23 was proposed to play a
crucial role in mediating tissue inflammation and autoimmunity. The present work
was aimed to investigate the relation between levels of IL-23 mRNA and disease
activity in patients with SLE and in those with renal involvement. In this work,
blood samples from 45 adult patients with SLE and 20 healthy controls were
collected. Patients were divided into 3 groups. Group I consisted of 16 patients
with active SLE with nephritis. Group II consisted of 13 patients with active SLE
without nephritis. Group III consisted of 16 patients with inactive SLE based on
the SLE disease activity index (SLEDAI). The IL-23 mRNA relative concentration
was detected by Quantitative Reverse transcriptase- polymerase Chain Reaction (RT
PCR). IL-23 mRNA expression level in blood was eleven times higher in SLE
patients without activity while in active SLE patients with and without nephritis
showed 34 fold and 17 fold higher IL-23 mRNA expression respectively compared to
healthy control. IL-23 mRNAs levels were significantly higher in patients with
SLE compared with healthy controls (P < 0.001). Patients with active disease
showed higher IL-23 mRNAs compared with those with inactive disease as well as
healthy controls (P < 0.001). IL-23 levels were significantly higher in SLE
patients with renal involvement compared with those without renal disease (P <
0.001). It is concluded that IL-23 has a role in the development and pathogenesis
of SLE & lupus nephritis.
PMID- 28502141
TI - Effect of Phototherapy on CD4, CD8 and Natural Killer Cells of Full Term Neonates
with Indirect Hyperbilirubinemia.
AB - Phototherapy is generally considered a very safe and well-tolerated treatment for
hyperbilirubinaemia. However, clinical users should be aware of the unwanted
effects of using phototherapy. Affection of neonatal immune system due to
phototherapy has been reported. This study aimed to evaluate the effect of
phototherapy on level of CD4+, CD8+ and natural killer (NK) (CD16+ & CD65+)
lymphocytes subsets in neonates. The number of these lymphocytes was measured 72
hrs after phototherapy exposure in 30 full term neonates with indirect
hyperbilirubinemia and compared to those of 25 healthy controls using flow
cytometry. Results showed non-significant changes of the tested lymphocyte
subsets after 72 hrs exposure to phototherapy. In conclusion, phototherapy has no
significant effect on the level of circulating CD4+, CD8+ and NK lymphocytes.
PMID- 28502142
TI - APRIL Level as a Marker of Disease Activity in Treated Rheumatoid Arthritis
Patients: Association with Disease Activity and Anti-CCP Antibody.
AB - Rheumatoid arthritis (RA) is a chronic autoimmune disease with joint inflammation
and autoantibody production. Cytokines play an important role in the pathogenesis
of RA. Among the cytokines that regulate B cell homeostasis is the "A
Proliferation-Inducing Ligand" (APRIL). To determine the differences in APRIL in
response to treatment in anti- cyclic citrllinated peptides (anti-CCP) positive
versus anti-CCP negative patients with established RA. Concentrations of APRIL in
sera of 10 anti-CCP positive RA patients, 18 anti-CCP negative RA patients, and
12 healthy controls were measured by enzyme-linked immunosorbent assay (ELISA) at
treatment initiation and after 6 months of treatment with methotrexate and
hydroxychloroquine. Correlations between serum anti-CCP, C-reactive protein
(CRP), erythrocyte sedimentation rate (ESR), 28-joint Disease Activity Score
(DAS28), and serum level of APRIL were analyzed. Serum APRIL levels were
increased in rheumatoid arthritis patients in comparison with healthy volunteers.
APRIL correlated positively with disease activity; swollen joint count, visual
analog score and simplified disease activity index (all P < 0.05). In addition,
APRIL was significantly higher in patients with positive anti-CCP. After
treatment, APRIL levels significantly decreased in the anti-CCP positive RA
patients than in anti-CCP negative RA patients. In conclusions, serum APRIL may
be a good predictor marker for joint injury and therapeutic response in patients
with RA.
PMID- 28502143
TI - Skin Prick Test Reactivity to Aeroallergens among Egyptian Patients with Isolated
Allergic Conjunctival Disease.
AB - Allergic conjunctival disease (ACD) is a type of ocular allergy, which includes
seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC),
and vernal keratoconjunctivitis (VKC). Little is known about the pattern of
sensitization or prevalent aeroallergens among patients with isolated ACD in
Egypt We aimed to evaluate the prevalence of skin prick test positivity to common
aeroallergens among Egyptian patients with isolated allergic conjunctival
disease. The study included 75 patients with isolated ACD recruited from a
tertiary Egyptian outpatient clinic. Skin prick test (SPT) was performed for all
patients with common aeroallergens. Total serum immunoglobulin E (IgE) was
measured by ELISA. A positive SPT reaction was present among 32 patients (42.7%).
The most prevalent aeroallergens among all patients were mites and pollens (12%
respectively), followed by grass (8%) and hay dust (6.7%). Eight patients (10.7%)
had SAC, 19 patients (25.3%) had PAC, and 48 patients (64%) had VKC. Prevalence
of SPT positivity to indoor allergens was significantly more common among PAC
(52.6%) than among SAC (25%) and VKC (16.7%), P= 0.011. Outdoor allergen
sensitization did not differ significantly between the 3 subgroups, P= 0.614.
Elevated IgE levels were observed among 62.5%, 73.7% and 66.7% of patients with
SAC, PAC and VKC, respectively, with no statistically significant difference
between them, P= 0.806. In conclusion aeroallergen sensitization is common among
Egyptian patients with isolated ACD. Accordingly, SPT should be included in the
diagnostic workup of these patients.
PMID- 28502144
TI - Risk Association between TNF-alpha-308 G>A and IL-6-174 G/C Polymorphisms and
Recurrent Transient Ischemic Attacks.
AB - Transient ischemic attack (TIA) is a brief cerebral ischemic incident. This study
assesses the role of TNF-alpha and IL-6 single nucleotide polymorphisms (SNPs) as
predictors of recurrent TIAs that have high risk of developing stroke. The
current study enrolled 54 high risk (according to frequency of TIA) TIA (group1),
52 low risk TIA patients (group2) and 34 controls (group3). Polymerase chain
reaction (PCR) for DNA amplification was done followed by restriction
endonuclease analysis to detect SNPs of TNF-alpha-308 G > A and IL-6-174 G/C. TNF
alpha serum level was analysed by ELISA. Significant increase of TNF-alpha-308 G
> A allele (group1 compared to group2 and control P=0.0001) and genotype TNF
alpha-308 AA (P<=0.05) were detected. IL6 allele polymorphism revealed
insignificant SNPs. The serum TNF-alpha was higher in group1 compared to control
and group2 and as well in TNF-alpha-308 AA variant in high risk group (P<=0.05).
It is concluded that TNF-alpha-308 G > A SNP might have a role in predicting
recurrent TIA with impact on preventive measures of stroke development.
PMID- 28502145
TI - Study of Interleukin 28B rs12979860 and rs8099917 Polymorphisms and T-helper 1
Response in Hepatitis C Virus Patients.
AB - HCV infection is a serious public health problem and a leading cause of chronic
liver disease. It affects nearly 3% of the world's population with an associated
high mortality. Egypt has the highest prevalence of HCV infection in the world
(estimated at >10%). Peg-IFN-alpha and RBV are the most widely used therapy for
HCV. Unfortunately, the rate of SVR is around 50%. In addition, it is expensive
and associated with considerable adverse effects. Thus selection of patients with
the highest probability of response is essential for clinical practice. It is
suggested that some SNPs near IL- 28B gene could be important genetic predictors
of treatment response among HCV. Our study aimed to study two different
Interleukin 28B polymorphisms (rs12979860 and rs8099917) and T-helper 1 response
in HCV infected patients. The current study was conducted on 60 chronic HCV
infected patients and 20 healthy volunteers. Grouping of patients was done
according to response to treatment into naive, responder and non-responder HCV
patients. Assessment of liver functions' tests, measuring HCV RNA levels using
real time PCR, measurement of interferon-gamma levels using ELISA and genotyping
of IL-28 rs2979860 and rs8099917 SNPs using 5' nuclease assay were done.
Concerning IL-28B rs12979860; TT genotype was highly expressed in non-responder
HCV patients but statistically insignificant. While for IL-28B rs8099917, there
was lack of association between its different genotypes and SVR. IFN-? level was
significantly increased among responder HCV patients carrying IL28B rs12979860 TT
genotype and/or IL28B rs8099917 GG allele. There was statistically significant
positive correlation between L28B rs8099917 GG genotype and HCV-RNA. In
conclusion, IL-28B rs12979860 SNP could be used as an independent predictor for
treatment response among HCV patients.
PMID- 28502146
TI - Brewer's Yeast Supplementation Enhances Immune Response of Aged Mice.
AB - A large amount of evidence indicates that aging is associated with immune system
dysfunction. Brewer's yeast, one of the most notable species of yeast in health
and wellness, has been shown to stimulate the immune system and improve human
life span. In the present study, brewer's yeast (5, 25 or 125 MUg/mouse) was
orally supplemented to aged mice each other day for 4 weeks. Total number of
leukocytes from peripheral blood (PBl), thymus (Thy), spleen (Sp), and peritoneal
exudate cells (PEC) were counted. Carbon clearance, plaque-forming cell and
rosette-forming cell assays were used to measure macrophage, B cell and T cell
responses. In vitro proliferation of splenocytes and histological architecture of
thymus from aged mice were tested. Yeast treated mice showed a significant
increase in the total number of PBl leukocytes, total cellularity of both Thy and
Sp, as well as a significant increase in total and differential numbers of PEC. A
gradual increase in macrophages' phagocytic activity of PEC and a significant
increase in both plaque-forming cell and rosette-forming cell responses were
observed. In vitro results showed that incubation of splenocytes with brewer's
yeast (0.5, 2.5 or 12.5MUg/well) in the presence of concanavalin-A mitogen
elicited a gradual increase in the proliferation of splenocytes. Histological
examination of thymuses from yeast-treated aged mice revealed that the cortex was
preferentially enlarged and repopulated with immature thymocytes. These results
indicate that brewer's yeast supplementation to aged mice improves several
baseline immune responses, and provides a valuable tool to identify nutritional
strategies that could mitigate immunosenescence.
PMID- 28502147
TI - Surface Expression and Genetic Variants of Toll-like Receptor 2 in Pulmonary
Tuberculosis Patients.
AB - Innate immunity plays an important role in the host defense against Mycobacterium
tuberculosis (M. tuberculosis). Toll-like receptor-2 (TLR2) is the main receptor
and one of central components in initiation of innate immunity against M.
tuberculosis. The study aimed to evaluate TLR2 surface expression on peripheral
blood monocytes and study its association with variants in TLR2 597T/C single
nucleotide polymorphisms (SNPs) in patients with pulmonary tuberculosis. Fifty
pulmonary tuberculosis patients and 50 healthy controls were investigated for
TLR2 expression on CD14+ monocytes by flow cytometry and TLR2 597T/C genotyping
by Tetra primer amplification refractory mutation system-polymerase chain
reaction (T-ARMS-PCR). A significant increase (P < 0.001) in TLR 2 expression was
detected in tuberculosis patients compared to controls. TLR2 597 TC and CC
genotypes were higher in pulmonary tuberculosis patients (OR =2.79, 95% CI =1.02
7.95 and OR =4.26, 95% CI =0.40-214.00) respectively. Genotype TT was associated
with reduced risk of being a case of pulmonary tuberculosis. There was no
association of TLR2 surface expression on monocytes in pulmonary tuberculosis
patients with different TLR2 597T/C genotypes. It is concluded that elevated
expression of TLR2 on CD14+ monocytes in pulmonary tuberculosis patients confirms
the role of TLR2 in host defense against M. tuberculosis. 597T/C polymorphism of
TLR 2 gene may be a risk factor for susceptibility to pulmonary tuberculosis in a
sample Egyptian population.
PMID- 28502148
TI - Sperm DNA Fragmentation Index and Intracytoplasmic Sperm Injection Outcome in
Egyptian Couples.
AB - Sperm of infertile men mostly contain more DNA damage than their fertile
counterparts. Sperm DNA damage might have a negative effect on the fertility
potential of such patients. This study measures the percentage of spermatozoa
with nuclear DNA fragmentation in semen samples used for intacytoplasmic sperm
injection (ICSI), before and after sperm processing and investigates the
association between sperm DNA fragmentation index (DFI) and ICSI outcome (embryo
grade and clinical pregnancy). Sperm DFI was measured, by TUNEL, in fresh semen
samples obtained from thirty male partners of infertile couples, seeking ICSI
treatment. The mean sperm DFI before and after processing was 4.5% and 8.83%
respectively. Sperm DFI increased significantly after processing (P < 0.001)
regardless the type of processing used (P= 0.877). The correlation between sperm
DFI, before and after semen processing, and clinical pregnancy was statistically
insignificant (P=0.689 and P=0.631 respectively). DFI of sperm after semen
processing showed a significant negative correlation with embryo grading at day 3
(r = - 0.232, P = 0.002). In conclusion, sperm DFI increases significantly after
processing and correlates negatively with embryo grade.
PMID- 28502149
TI - Serum Level of Interleukin-37 and Expression of Its mRNA in Ankylosing
Spondylitis Patients: Possible Role in Osteoporosis.
AB - Ankylosing spondylitis (AS) is a chronic inflammatory disease of the axial
skeleton.Interleukin-37 (IL-37) is a member of IL-1 family cytokines, that
downregulate expression of pro-inflammatory cytokines in chronic inflammatory
diseases. The aim of the work is to investigate role of IL-37 in AS disease
activity and osteoporosis. Twenty-five patients with AS and 25 controls were
enrolled into this study. They were subjected to full clinical examination
including assessment of disease activity according to the Bath Ankylosing
Spondylitis Disease Activity Index (BASDAI). Serum IL-37 levels and IL-37 mRNA
relative concentration were measured by enzyme-linked immunosorbent assay (ELISA)
and quantitative reverse transcriptase- polymerase chain reaction (RT-PCR)
respectively. Bone mineral density (BMD) was determined using dual energy X-ray
absorptiometry (DEXA). Spine radiographs were scored using the modified Stoke
Ankylosing Spondylitis Spine Score (mSASSS). Mean serum IL-37 level was
significantly higher in AS patients compared with the controls (P < 0.001) and
significantly elevated in AS patients with osteoporosis (P < 0.05). IL-37 mRNA
gene expression showed a significant increase expression in active AS patient (25
folds) as well as in inactive patient (12 folds) as compared to controls. In
conclusion, serum IL-37 and its mRNA expression is increased in AS patients with
special consideration in patient with Osteoporosis and correlates with disease
activity and BMD which indicate that IL-37 may provide a novel research target
for pathogenesis and therapy of AS..
PMID- 28502150
TI - Suspected Allergic Bronchopulmonary Aspergillosis Cases in Adult Bronchial Asthma
Patients Attending a Tertiary Care Clinic.
AB - Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to
Aspergillus species (generally Aspergillus fumigatus) that occurs almost
exclusively in patients with asthma or, less commonly, cystic fibrosis. Immune
responses to Aspergillus antigens cause airway obstruction and, if untreated,
bronchiectasis and pulmonary fibrosis. Our objective was to define the clinical
characteristics, laboratory and radiological findings of suspected ABPA cases
among a cohort of Egyptian patients with bronchial asthma. 52 moderate and severe
asthma patients were recruited from the Allergy and Immunology clinic at Ain
Shams University hospitals. Patients were subjected to history taking for asthma
symptoms, skin test with Aspergillus fumigatus antigen, total IgE level,
peripheral blood eosinophilia, chest x-ray and high resolution CT chest. 27
patients had positive skin prick and /or intradermal test to Aspergillus
fumigatus antigen, and 11 (21.2%) of them fulfilled 4 of the criteria for ABPA
diagnosis. Patients with suspected ABPA had significantly higher serum total IgE
levels (median (IQR) = 625 IU/ml (514.9-762) with P-value <0.0001). Our study
suggests a high frequency of suspected ABPA cases for further confirmation by
appropriate diagnostic tests; there is a need for better recognition of ABPA as
it is yet under recognized in Egypt Clinicians ought to have a high index of
suspicion for ABPA while managing any patient with bronchial asthma to detect
ABPA prior to development of irreversible complications.
PMID- 28502151
TI - Percentage of CD3-CD56+dim and of CD3-CD56+dimCD69+ Natural Killer Cells in the
Peripheral Blood of Women with In Vitro Fertilization (IVF) Failure.
AB - CD56dim cells, potent mediators of natural cytotoxicity, have direct contact with
chorionic villi at the intervillous space. The manner the developing fetus evades
NK cytotoxicity from these cells may determine the pregnancy outcome. CD69 is one
of the earliest cell surface activation markers expressed by NK cells. In vitro
models demonstrated that activated CD69+ NK cells are capable of lysing
trophoblasts. This study aimed to investigate the relation between the percentage
of these NK cells in peripheral blood and infertility. The study included two
groups, each of 30 women, one with previous implantation failure and a fertile
matching control group. CD3-CD56+dim and CD3-CD56+dimCD69+ NK were analyzed by
flow cytometry. A higher percentage of CD3-CD56+dim and CD3-CD56+dimCD69+ in the
study group than the control group was observed (P=0.0001 and P=0.003,
respectively). Fair predictive values were evidenced by ROC curve analysis. We
conclude that increase in CD56+dim NK and CD56+dim CD69+ NK cell percentages may
be related to infertility problems.
PMID- 28502152
TI - Assessment of Nasal Immunoglobulin E Level in Atopic and Non-atopic Rhinitis
Patients: A Tool for Diagnosis of Local Allergic Rhinitis.
AB - Many cases of AR can be miss-diagnosed due to deficiency in the conventional
laboratory tools. Detection of local Ig E immune response and allergy associated
genes may aid in diagnosis of these cases. The local immune response and the
allergy associated genes of these suspected cases must be evaluated as they may
help in their characterization. This study was conducted on 129 patients with
chronic rhinitis to determine the frequency of LAR, and analyze the association
of IgE receptor (FcepsilonR1beta) gene polymorphism with LAR. All participants
were subjected to clinical questionnaire, skin prick test, specific IgE
measurement in serum and nasal secretions and analysis of FcepsilonR1beta gene
polymorphism. LAR constituted 24.8 % of total rhinitis cases and 44.4% of non
allergic cases. Cockroach was the main sensitizing agent in local allergic
rhinitis in comparison with allergic cases (OR =0.11; 95% CI= 0.04-0.34;
P<0.001). In LAR, nasal specific Ig E was significantly lower than that in AR
patients (P < 0.001). FcepsilonR1beta genotype TT was more frequently expressed
in LAR and AR than non-allergic rhinitis (NAR) (P< 0.001). It is concluded that
LAR is an emerging allergic condition that could be diagnosed by nasal specific
IgE, and that FcepsilonR1beta polymorphism is one of the genetic factors
associated with AR and LAR.
PMID- 28502153
TI - Immunotherapeutic Approach to Breast Cancer: The Anti-Tumor Effect of Anti-IL-6
Monoclonal Antibodies in Malignant Mammary Tumor Implanted-Mice.
AB - It has been established that suppression of apoptosis during carcinogenesis is
the main cause of development and progression of breast cancer. Breast cancer
patients have higher circulating levels of IL-6 protecting cancer cells from
apoptosis and positively correlated with poor prognosis of the disease. The
current work is carried out to fulfill one of our in vivo preclinical studies'
for approaching a novel breast cancer immunotherapy through induction of tumor
cell apoptosis. The study aims at investigating the potential of anti-IL-6
monoclonal antibodies (mAbs) to suppress IL-6 anti-apoptotic activities in tumor
microenvironment of malignant mammary tumor implanted-mice. To achieve this goal,
4 groups of mice were used, group I: served as control, group II: mice implanted
with Ehrlich ascites carcinoma cell lines (EAC), through intramuscular injection
till tumor inoculation, group III: injected intratumorally with10 ul saline for 3
successive days, and group IV: mice were injected intratumorally one day after
tumor inoculation with a dose of 1.5 mg / kg of recombinent anti-IL-6 monoclonal
antibodies in10 ul saline for 3 successive days. Apoptosis was evaluated in tumor
samples from anti-IL-6 treated tumor implanted mice and compared with controls.
Levels of apoptosis in tumor tissue samples of tumor implanted mice treated with
anti-IL-6 were significantly (P=0.009) higher than untreated ones. In conclusion,
anti-IL-6 monoclonal antibodies have the potential to suppress the anti-apoptotic
effect of interleukin-6 (IL-6) within the tumor microenvironment of tumor
implanted in mice.
PMID- 28502154
TI - Helicobacter pylori Infection as a Risk Factor in Patients Suffering from Food
Allergy and Urticaria.
AB - H. pylori infection is common worldwide. Many intestinal and extra intestinal
manifestations have been associated with H. pylori infection. H. pylori destruct
the gastric lining which allows food allergens to get access to blood,
predisposing to Food allergy. Previous works considered chronic urticaria as a
known symptom for food allergy and a skin manifestation for H. pylori infection.
The aim of this work is to provide evidence based recommendation for detecting H.
pylori antigen in stool in patient suffering from both food allergy and chronic
urticaria. We determined the frequency of H. pylori Ag in stool in a group of
patients complaining from both disorders and compared it with a group of
apparently healthy control subjects with no history of either urticaria or food
allergy. Our results showed that the frequency of H. pylori Ag in stool in
control group was 62.5 %, while, it was 97 % in patient group. When we calculated
the risk of H. pylori infection in predisposing to both disorders, odds ratio was
18.6. According to these results we concluded that H. pylori is a risk factor for
developing chronic urticaria and food allergy and we recommend testing for H.
pylori Ag in stool in patients complaining from these disorders.
PMID- 28502155
TI - Serum Anti-TPO and TPO Gene Polymorphism as a Predictive Factor for Hidden
Autoimmune Thyroiditis in Patient with Bronchial Asthma and Allergic Rhinitis.
AB - Thyroid peroxidase (TPO) is the key enzyme in the biosynthesis of thyroid
hormones T3 and T4. Autoimmune thyroiditis is a common disorder affecting 10% of
population worldwide. A key feature of autoimmune thyroiditis is the presence of
anti TPO antibodies, and some mutation of the TPO gene. Association between
autoimmune thyroiditis and other autoimmune disorders has been reported but
little is known about association with allergic diseases. In this study, we aimed
to evaluate frequency of hidden autoimmune thyroiditis among allergic patient and
examine possible relationship between anti-TPO levels and polymorphism at the TPO
gene A2173/C exon 12 and different types of allergens. The study included 50
adult Egyptian patients with allergic rhinitis and /or bronchial asthma and 50
controls. For each subject, thyroid stimulating hormone (TSH), thyroxin 4 (T4)
and Triiodothyronine (T3) hormones were measured. Anti-thyroid peroxidase (anti
TPO) level was detected by ELISA; and TPO gene polymorphism 2173A>C exon 12 was
analyzed using restriction fragment length polymorphism (RFLP). Skin prick test
was done to assess allergic response in patients. Serum levels of T3, T4 and TSH
did not show any statistical significant difference between patients and groups.
However, mean serum anti-TPO level was statistically higher in patients than
controls, and correlated positively with body mass index, age, diastolic blood
pressure, suggesting higher prevalence of hidden autoimmune thyroiditis in
allergic patients than in control group. 2173A>C Genotyping revealed that the
frequency of C allele is increased in the patient group. C allele represents a
risk factor with odds ratio of 2.37 (1.035-5.44) and a significant P value <0.05.
It is concluded that TPO 2173A>C polymorphism may be considered as a risk factor
for developing autoimmune thyroiditis in patients with allergic rhinitis and
asthma and that these patients should regularly be checked for hidden
thyroiditis.
PMID- 28502156
TI - HCV Infection Amplified Th2 Bias and Th17 Responses In Schistosoma-Infected
Patients.
AB - Schistosomiasis and HCV are the most prevalent infections in Egypt Schistosoma
infection is associated with bias towards Th2 responses. Plasma from 17
(Schistosoma-infected), 39 (Schistosoma/HCV co-infected) and 23 controls were
collected. Cytokine multiplex array was used to measure 6 plasma cytokine levels
representing the surrogate markers of three T helper lymphocytes subpopulations;
IL-12 (Th1), IL-4 and IL-10 (Th2), IL-17, IL-22 and IL-23 (Th17). There was a
significant increase in plasma levels of IL-17 and IL-23 in co-infected patients
compared to Schistosoma-infected patients. As well, there was a significant
increase in the Th2 regulatory cytokines IL-10 and IL-4 in co-infected group
compared to Schistosoma-infected patients. However, no significant changes were
observed in the Th1 cytokine (IL-12) among the groups. In conclusion, presence of
HCV infection shifted the response towards Th2/Th17 pathway which may play a role
in the progressive pathogenesis of HCV in Schistosoma-co-infected patients.
PMID- 28502157
TI - Study of Serum Immunoglobulin Levels and T lymphocyte Subsets in Children with
Beta Thalassemia with Iron Overload in Egypt.
AB - Beta thalassemia is an inherited hemoglobin disorder resulting in chronic
hemolytic anemia that requires lifelong transfusion therapy. Repeated blood
transfusions and RBCs hemolysis are the main causes of iron overload, which in
addition to immune abnormalities, are common predisposing factors to infection in
patients with thalassemia. The aim was to study serum immunoglobulin levels and T
lymphocyte subsets in children with beta- thalassemia in relation to iron
overload. This study was conducted on 40 children with beta thalassemia major
including 24 males and 16 females with mean age of 9.22 +/- 3.9 and 20 healthy
children of matched age and sex as a control. All children were subjected to
assessment of infection episodes, complete blood picture, Hb electrophoresis,
serum iron status, T cell subsets including CD3, CD4 and CD8 using Becton
Dickinson FAC Scan flow cytometer and serum immunoglobulin levels including IgM,
IgA and IgG by a commercial nephelometry assay using a BN-II device. Serum
ferritin and iron were significantly higher but total iron binding capacity was
significantly lower in patients than controls (Mean serum ferritin was 3418.23+/
2950.7 in the studied patients versus 39.48+/-2.48 in the control group with p
value of 0.00, mean serum iron was 222+/-56.61 in the studied patients versus
90+/-31.87 in the control group with P value of 0.00 and mean serum total iron
binding capacity was 198.38+/-19.9in the studied patients versus 315.7+/-24.85 in
the control group with P value of 0.00). CD3 and CD4 were significantly lower but
CD8 was significantly higher in patients than controls. The count (mean +/- SD
cells/ mm2) for CD3+, CD4+ and CD8+ T cells in patients was 1733.25 +/- 381.87,
889.67 +/- 282.86 and 779.72 +/- 390.63 respectively as compared to 1887 +/-
390.56, 1003 +/- 250.96 and 663 +/- 116.71 in the control group respectively (P
values 0.00, 0.048 and, 0.02 respectively). The mean +/- SD (mg/dl) of serum
immunoglobulin's G, M and A showed significant variation between patients and
controls including significantly lower IgM and significantly higher IgG, and IgA
in patients than controls with P values of 0.014, 0.049 and 0.020 for G, M, and A
respectively).There were significant negative correlations between CD3, CD4, IgM
and ferritin and significant positive correlations between CD8, IgG, IgA and
ferritin. In conclusion; Iron overload affects humeral and cell mediated immunity
in thalassemic patients therefore regular follow up for iron overload is
recommended.
PMID- 28502158
TI - Significance of Anti-C1q Antibodies in Patients with Systemic Lupus Erythematosus
as A Marker of Disease Activity and Lupus Nephritis.
AB - Anti-C1q autoantibodies have been proposed as a useful marker in SLE. This study
aimed at measuring serum levels of anti-C1q antibodies in patients with SLE and
investigates correlations of this level with the histopathological classes of
renal biopsies and disease activity. The anti-C1q antibody level was measured in
30 females SLE patients and 20 controls. The activity of SLE disease was
calculated according to the SLE disease activity index. A renal biopsy from
patients with clinical manifestations of renal disease was obtained. There was a
significant increase in the level of anti-C1q antibodies in SLE patients than
controls and in patients with active LN than inactive LN (P<0.05). There were
significant positive correlations between anti-C1q antibody level and SLEDAI &
rSLEDAI scores and activity index score of renal biopsies. Anti-C1q antibodies
showed higher diagnostic sensitivity and specificity than anti-dsDNA antibodies.
In conclusion, anti-C1q antibodies are useful and sensitive non-invasive
biomarker with high specificity in combination with anti-dsDNA antibodies for the
diagnosis of renal disease activity.
PMID- 28502160
TI - Sarcoidosis with splenic involvement diagnosed via endoscopic ultrasound-guided
fine-needle biopsy.
PMID- 28502159
TI - LPL gene Pvu II polymorphism and hypertriglyceridemia: a meta-analysis involving
1,640 subjects.
AB - BACKGROUND/AIMS: Although lipoprotein lipase (LPL) gene Pvu II polymorphism has
been associated with an increased risk of hypertriglyceridemia (HT), there is no
clear consensus within the scientific community. METHODS: A meta-analysis of
1,640 subjects from six individual studies was conducted to better elucidate the
potential relationship between the LPL gene Pvu II polymorphism and HT within the
Chinese population. Pooled odds ratios (ORs) and their corresponding 95%
confidence intervals (CIs) were evaluated by using fixed effect models. RESULTS:
Our analysis indicated a significant association between LPL gene Pvu II
polymorphism and HT within the Chinese population under allelic (OR, 1.550; 95%
CI, 1.320 to 1.830; p = 1.158 * 10-7), recessive (OR, 0.540; 95% CI, 0.390 to
0.750; p = 0.0002), dominant (OR, 1.889; 95% CI, 1.501 to 2.377; p = 5.960 * 10
8), homozygous (OR, 2.167; 95% CI, 1.531 to 3.067; p = 1.242 * 10-5),
heterozygous (OR, 1.810; 95% CI, 1.419 to 2.309; p = 1.842 * 10-6), and additive
genetic models (OR, 1.553; 95% CI, 1.320 to 1.828; p = 1.158 * 10-7).
CONCLUSIONS: Because LPL gene Pvu II restriction fragment length polymorphism
polymorphism was associated with an elevated risk of HT, the P+ allele carriers
of the LPL gene might be predisposed to HT.
PMID- 28502161
TI - Formation and Inhibition of Metallic Lithium Microstructures in Lithium Batteries
Driven by Chemical Crossover.
AB - The formation of metallic lithium microstructures in the form of dendrites or
mosses at the surface of anode electrodes (e.g., lithium metal, graphite, and
silicon) leads to rapid capacity fade and poses grave safety risks in
rechargeable lithium batteries. We present here a direct, relative quantitative
analysis of lithium deposition on graphite anodes in pouch cells under normal
operating conditions, paired with a model cathode material, the layered nickel
rich oxide LiNi0.61Co0.12Mn0.27O2, over the course of 3000 charge-discharge
cycles. Secondary-ion mass spectrometry chemically dissects the solid-electrolyte
interphase (SEI) on extensively cycled graphite with virtually atomic depth
resolution and reveals substantial growth of Li-metal deposits. With the absence
of apparent kinetic (e.g., fast charging) or stoichiometric restraints (e.g.,
overcharge) during cycling, we show lithium deposition on graphite is triggered
by certain transition-metal ions (manganese in particular) dissolved from the
cathode in a disrupted SEI. This insidious effect is found to initiate at a very
early stage of cell operation (<200 cycles) and can be effectively inhibited by
substituting a small amount of aluminum (~1 mol %) in the cathode, resulting in
much reduced transition-metal dissolution and drastically improved cyclability.
Our results may also be applicable to studying the unstable electrodeposition of
lithium on other substrates, including Li metal.
PMID- 28502162
TI - Identification of Major Sources of Atmospheric NH3 in an Urban Environment in
Northern China During Wintertime.
AB - To assess the relative contributions of traffic emission and other potential
sources to high levels of atmospheric ammonia (NH3) in urban areas in the
wintertime, atmospheric NH3 and related pollutants were measured at an urban
site, ~300 m from a major traffic road, in northern China in November and
December 2015. Hourly average NH3 varied from 0.3 to 10.8 ppb with an average of
2.4 ppb during the campaign. Contrary to the common perspective in literature,
traffic emission was demonstrated to be a negligible contributor to atmospheric
NH3. Atmospheric NH3 correlated well with ambient water vapor during many time
periods lasting from tens of hours to several days, implying NH3 released from
water evaporation is an important source. Emissions from local green space inside
the urban areas were identified to significantly contribute to the observed
atmospheric NH3 during ~60% of the sampling times. Evaporation of predeposited
NHx through wet precipitation combined with emissions from local green space
likely caused the spikes of atmospheric NH3 mostly occurring 1-4 h after morning
rush hours or after and during slight shower events. There are still ~30% of the
data samples with appreciable NH3 level for which major contributors are yet to
be identified.
PMID- 28502163
TI - Constraining the Spatial Extent of Marine Oil Snow Sedimentation and Flocculent
Accumulation Following the Deepwater Horizon Event Using an Excess 210Pb Flux
Approach.
AB - Following the Deepwater Horizon (DWH) event in 2010, there were several lines of
evidence indicating the presence of marine oil snow sedimentation and flocculent
accumulation (MOSSFA). A significant amount of marine oil snow formed in the
water column of the northern Gulf of Mexico (nGoM), settled rapidly, and
ultimately accumulated in the sediments of the nGoM. This study utilized a
commonly used radioisotope tracer (excess 210Pb, 210Pbxs) from 32 sediment cores
collected from 2010 to 2013 to characterize the spatial extent of MOSSFA on the
seafloor. Relative to pre-DWH conditions, an increase in 210Pbxs flux occurred in
two distinct regions: (1) in the western portion of the study area on an east
northeast to west-southwest axis, stretching 230 km southwest and 140 km
northeast of the DWH wellhead, and (2) in the eastern portion of the study area
on a 70 km northeast to southwest axis near the DeSoto Canyon. The total
sedimentary spatial extent of MOSSFA, as calculated by increased 210Pbxs flux
after 2010, ranged from 12 805 to 35 425 km2. 210Pbxs flux provides a valuable
tool for documenting the spatial extent of MOSSFA following DWH and will continue
to aid in the determination of advective transport and ultimate depocenters of
MOSSFA material.
PMID- 28502165
TI - Grape Seed Proanthocyanidin Inhibits Mucin Synthesis and Viral Replication by
Suppression of AP-1 and NF-kappaB via p38 MAPKs/JNK Signaling Pathways in
Respiratory Syncytial Virus-Infected A549 Cells.
AB - Airway epithelial cells are often infected by respiratory syncytial virus (RSV),
one of the most common causes of asthma, bronchiolitis, chronic obstructive
pulmonary disease, and pneumonia. During the infection process, excessive mucins
instigate airway inflammation. However, the mechanism underlying RSV-induced
airway hyper-responsiveness and inflammation is poorly understood. Furthermore,
no reliable vaccines or drugs for antiviral therapy are available. In this study,
the effect of the natural compound grape seed proanthocyanidin (GSP) on RSV
infected human airway epithelial cells A549 was evaluated. After pretreatment of
the cells with or without exposure to RSV with 5-10 MUg GSP/mL, the expression of
various mucins (MUC1, MUC2, MUC5AC, MUC5B, and MUC8) was evaluated by real-time
polymerase chain reaction, enzyme-linked immunosorbent assay, and Western
blotting, as well as confocal microscopy. We found that GSP significantly
decreased RSV-induced mucin synthesis at the mRNA and protein levels. In
addition, GSP suppressed the RSV-induced signaling pathways, including
extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38, together
with nuclear factor kappa B (NF-kappaB) and activating protein-1 family members
(c-Jun and c-Fos). Concomitantly, GSP inhibited the replication of RSV within
A549 cells. Taken together, all our results suggest that GSP could be a potent
therapeutic agent to suppress excessive mucus production and viral replication in
RSV-induced airway inflammatory disorders.
PMID- 28502164
TI - Direct 11CN-Labeling of Unprotected Peptides via Palladium-Mediated Sequential
Cross-Coupling Reactions.
AB - A practical procedure for 11CN-labeling of unprotected peptides has been
developed. The method was shown to be highly chemoselective for cysteine over
other potentially nucleophilic residues, and the radiolabeled products were
synthesized and purified in less than 15 min. Appropriate for biomedical
applications, the method could be used on an extremely small scale (20 nmol) with
a high radiochemical yield. The success of the protocol stems from the use of a
Pd-reagent based on a dihaloarene, which enables direct "nucleophile-nucleophile"
coupling of the peptide and [11C]cyanide by temporal separation of nucleophile
addition.
PMID- 28502166
TI - Grouping of Petroleum Substances as Example UVCBs by Ion Mobility-Mass
Spectrometry to Enable Chemical Composition-Based Read-Across.
AB - Substances of Unknown or Variable composition, Complex reaction products, and
Biological materials (UVCBs), including many refined petroleum products, present
a major challenge in regulatory submissions under the EU Registration,
Evaluation, Authorisation and Restriction of Chemicals (REACH) and US High
Production Volume regulatory regimes. The inherent complexity of these
substances, as well as variability in composition obfuscates detailed chemical
characterization of each individual substance and their grouping for human and
environmental health evaluation through read-across. In this study, we applied
ion mobility mass spectrometry in conjunction with cheminformatics-based data
integration and visualization to derive substance-specific signatures based on
the distribution and abundance of various heteroatom classes. We used petroleum
substances from four petroleum substance manufacturing streams and evaluated
their chemical composition similarity based on high-dimensional substance
specific quantitative parameters including m/z distribution, drift time, carbon
number range, and associated double bond equivalents and hydrogen-to-carbon
ratios. Data integration and visualization revealed group-specific similarities
for petroleum substances. Observed differences within a product group were
indicative of batch- or manufacturer-dependent variation. We demonstrate how high
resolution analytical chemistry approaches can be used effectively to support
categorization of UVCBs based on their heteroatom composition and how such data
can be used in regulatory decision-making.
PMID- 28502167
TI - Transient Porosity in Densely Packed Crystalline Carbazole-(p-Diethynylphenylene)
Carbazole Rotors: CO2 and Acetone Sorption Properties.
AB - We report for the first time the high sorption properties of a molecular rotor
with no permanent voids or channels in its crystal structure. Such crystalline
phase originates from THF, DCM, or the irreversible desolvation of entrapped
benzene molecules. From these, the benzene in its solvate form acts as rotation
stopper, as supported by dynamic characterization using solid-state 2H NMR
experiments. In the solvent-free form, the diffusion of small quantities of
iodine vapors caused a significant change in the intramolecular rotation,
increasing the known activation energy to rotation from 8.5 to 10.6 kcal mol-1.
Notably, those results paved the way for the discovery of the high CO2 uptake
(201.6 cm3 g-1 at 196 K, under 1 atm) and acetone (5 wt %), a sorption property
that was attributed to both, the restriction of the molecular rotation at low
temperatures and the flexibility of the molecular axle made of conjugated p
(ethynylphenylene), surrounded by carbazole.
PMID- 28502168
TI - Age Dating of Individual Micrometer-Sized Uranium Particles by Secondary Ion Mass
Spectrometry: An Additional Fingerprint for Nuclear Safeguards Purposes.
AB - A direct and simultaneous analysis of the age and isotopic composition of nuclear
material at the particle scale is described in this study. By comparison with
other conventional techniques such as inductively-coupled plasma mass
spectrometry or thermal-ionization mass spectrometry, secondary ion mass
spectrometry enables one to determine the ages of individual particles in a
mixture of nuclear materials. Having access to the purification date can give
precious information on the history of a nuclear facility or nuclear material for
safeguarding purposes. The high sensitivity of this technique combined with its
imaging capabilities enables one to detect and to sort out all particles
according to their isotopic composition in one analysis. The succession of two
microbeam analyses on an individual particle allows the determination of the
precise 235U abundance and the model age. The methodology was successfully
applied to a mixture of uranium particles coming from certified reference
material with a 235U abundance ranging from 10% to 97%: the accuracy on the 235U
abundance is greater than 0.5% and the accuracies on the 235U abundance and the
model age are better than 0.5% and 3%, respectively.
PMID- 28502169
TI - Direct Conjugation of Emerging Contaminants in Arabidopsis: Indication for an
Overlooked Risk in Plants?
AB - Agricultural use of treated wastewater, biosolids, and animal wastes introduces a
multitude of contaminants of emerging concerns (CECs) into the soil-plant system.
The potential for food crops to accumulate CECs depends largely on their
metabolism in plants, which at present is poorly understood. Here, we evaluated
the metabolism of naproxen and ibuprofen, two of the most-used human drugs from
the Profen family, in Arabidopsis thaliana cells and the Arabidopsis plant. The
complementary use of high-resolution mass spectrometry and 14C labeling allowed
the characterization of both free and conjugated metabolites, as well as
nonextractable residues. Naproxen and ibuprofen, in their parent form, were
conjugated quickly and directly with glutamic acid and glutamine, and further
with peptides, in A. thaliana cells. For example, after 120 h, the metabolites of
naproxen accounted for >90% of the extractable chemical mass, while the intact
parent itself was negligible. The structures of glutamate and glutamine
conjugates were confirmed using synthesized standards and further verified in
whole plants. Amino acid conjugates may easily deconjugate, releasing the parent
molecule. This finding highlights the possibility that the bioactivity of such
CECs may be effectively preserved through direct conjugation, a previously
overlooked risk. Many other CECs are also carboxylic acids, such as the profens.
Therefore, direct conjugation may be a common route for plant metabolism of these
CECs, making it imperative to consider conjugates when assessing their risks.
PMID- 28502171
TI - Complexation of a Globular Protein, beta-Lactoglobulin, with an Anionic
Surfactant in Aqueous Solution.
AB - The complexation of a globular protein, beta-lactoglobulin (BLG), and an anionic
surfactant sodium dodecyl sulfate (SDS) in aqueous media was investigated using
capillary zone electrophoresis, electrophoretic, static, and dynamic light
scattering, and small-angle X-ray scattering in a considerably high protein
concentration range (0.27 mM < CP < 3 mM). On increasing the molar concentration
CR of the surfactant, cooperative binding of SDS to BLG starts at CR/CP ~ 1; the
BLG-SDS complex consists mainly of the BLG dimer and approximately 20 SDS
molecules, where BLG takes a compact conformation similar to that of the native
BLG up to CR/CP ~ 20. At CR/CP higher than 30, the BLG dimer in the BLG-SDS
complex dissociates into a unimer, but the dissociated BLG unimer still takes a
compact conformation at least at 30 < CR/CP < 65.
PMID- 28502170
TI - A Low-Energy Ion Scattering Approach for Studying Au Nanoclusters Grown on an H2O
Buffer Layer.
AB - A novel form of alkali low-energy ion scattering is used to probe the deposition
of nanoclusters onto a solid surface via buffer layer assisted growth (BLAG) in
ultrahigh vacuum. A thin amorphous solid water (ASW) buffer layer is grown on a
TiO2(110) single crystal cooled to 100 K. Au atoms deposited onto this layer
arrange themselves into nanoclusters. The sample is then annealed to 320 K to
desorb the ASW and enable the clusters to soft-land onto the substrate. Time-of
flight low-energy ion scattering, using Li+, Na+, and K+ projectiles, probes the
materials during each step of the BLAG process to measure the surface composition
and reveal the details of how the clusters form. The neutralization probability
of Na+ ions singly scattered from the Au nanoclusters indicates that they
increase in size after annealing and that the magnitude of the increase is a
function of the buffer layer thickness. The adsorption of a thin, incomplete
water layer prior to Au deposition forms nanoclusters that are possibly even
smaller than those produced by direct deposition onto the clean substrate.
PMID- 28502172
TI - Direct Dopant Patterning by a Remote Monolayer Doping Enabled by a Monolayer
Fragmentation Study.
AB - The development of new doping methods extending beyond the traditional and well
established techniques is desired to match the rapid advances made in
semiconductor (SC)-processing methods and nanostructure synthesis in numerous
emerging applications, including the doping of 3D architectures. To address this,
monolayer doping (MLD) and monolayer contact doping methods have been introduced
recently. The MLD methods enable separation of the doping process of
nanostructures from the synthesis step; hence, it is termed ex situ doping. Here,
we present a new ex situ MLD method termed remote MLD (R-MLD). The noncontact
doping method is based on the thermal fragmentation of dopant-containing
monolayers and evaporation processes taking place during annealing of the
uncapped monolayer dopant source positioned in proximity, however, without making
physical contact with the target SC surface. We present a two-step annealing
procedure that allows the study of the dopant monolayer fragmentation and
evaporation stages and quantification of the doping levels obtained during each
step. We demonstrate the application of R-MLD for achieving a large-scale direct
patterning of silicon substrates with sharp doping profiles. The direct dopant
patterning is obtained without applying lithographic processing steps to the
target substrate. The noncontact doping process, monolayer decomposition, and
fragment evaporation were studied using thermogravimetric analysis coupled with
mass spectrometry and sheet resistance measurements. The doped patterns were
characterized using scanning electron microscopy, scanning capacitance
microscopy, and time-of-flight secondary ion mass spectroscopy.
PMID- 28502173
TI - Isolated Single-Atom Pd Sites in Intermetallic Nanostructures: High Catalytic
Selectivity for Semihydrogenation of Alkynes.
AB - Improving the catalytic selectivity of Pd catalysts is of key importance for
various industrial processes and remains a challenge so far. Given the unique
properties of single-atom catalysts, isolating contiguous Pd atoms into a single
Pd site with another metal to form intermetallic structures is an effective way
to endow Pd with high catalytic selectivity and to stabilize the single site with
the intermetallic structures. Based on density functional theory modeling, we
demonstrate that the (110) surface of Pm3m PdIn with single-atom Pd sites shows
high selectivity for semihydrogenation of acetylene, whereas the (111) surface of
P4/mmm Pd3In with Pd trimer sites shows low selectivity. This idea has been
further validated by experimental results that intermetallic PdIn nanocrystals
mainly exposing the (110) surface exhibit much higher selectivity for acetylene
hydrogenation than Pd3In nanocrystals mainly exposing the (111) surface (92% vs
21% ethylene selectivity at 90 degrees C). This work provides insight for
rational design of bimetallic metal catalysts with specific catalytic properties.
PMID- 28502174
TI - Bimetallic Au/Ag Core-Shell Superstructures with Tunable Surface Plasmon
Resonance in the Near-Infrared Region and High Performance Surface-Enhanced Raman
Scattering.
AB - Due to the larger surface area and the synergistic effects between two noble
metals, the bimetallic superstructures exhibit enhanced distinctive optical,
catalytic, and photothermal performances and surface-enhanced Raman scattering
(SERS) "hot-spot" effect, and thus have attracted great interest in various
applications. Compared with the common Pd, Pt hierarchical structures coated onto
Au nanoparticles (NPs), easily synthesized via fast autocatalytic surface growth
arising from intrinsic properties of Pd and Pt metals, precisely controlling the
hierarchical Ag growth onto Au NPs is rarely reported. In our present study, the
reducing agent dopamine dithiocarbamate (DDTC) was covalently capped onto the
first metal core (Au) to delicately control the growth model of the second metal
(Ag). This results in heterogeneous nucleation and growth of Ag precursor on the
surface of Au nanorods (NRs), and further formation of cornlike bimetallic Au/Ag
core-shell superstructures, which usually cannot be achieved from traditional
epitaxial growth. The thickness of the hierarchical Ag shell was finely tuned in
a size range from 8 to 22 nm by simply varying the amount of the ratio between Ag
ions and DDTC capped on Au NR core. The tunable Ag shell leads to anisotropic
bimetallic Au/Ag core-shell superstructures, displaying two distinctive plasmonic
resonances in the near-infrared region (NIR). In particular, the longitudinal
surface plasmon resonance exhibits a broadly tunable range from 840 to 1277 nm.
Additionally, the rich hot spots from obtained Au/Ag superstructures
significantly enhance the SERS performance.
PMID- 28502175
TI - London Dispersion Enables the Shortest Intermolecular Hydrocarbon H...H Contact.
AB - Neutron diffraction of tri(3,5-tert-butylphenyl)methane at 20 K reveals an
intermolecular C-H...H-C distance of only 1.566(5) A, which is the shortest
reported to date. The compound crystallizes as a C3-symmetric dimer in an unusual
head-to-head fashion. Quantum chemical computations of the solid state at the HSE
3c level of theory reproduce the structure and the close contact well (1.555 A at
0 K) and emphasize the significance of packing effects; the gas-phase dimer
structure at the same level shows a 1.634 A C-H...H-C distance. Intermolecular
London dispersion interactions between contacting tert-butyl substituents
surrounding the central contact deliver the decisive energetic contributions to
enable this remarkable bonding situation.
PMID- 28502176
TI - Effect of Glutathione on the Taste and Texture of Type I Sourdough Bread.
AB - Type I sourdough fermentations with Lactobacillus sanfranciscensis as predominant
organism accumulate reduced glutathione through glutathione reductase (GshR)
activity of L. sanfranciscensis. Reduced glutathione acts as chain terminator for
gluten polymerization but is also kokumi-active and may thus enhance bread taste.
This study implemented a type I model sourdough fermentations to quantitate
glutathione accumulation sourdough, bread dough, and bread and to assess the
effect of L. sanfranciscensis GshR on bread volume by comparison of L.
sanfranciscensis and an isogenic strain devoid of GshR. L. sanfranciscensis
sourdough accumulated the highest amount of reduced glutathione during proofing.
Bread produced with the wild type strain had a lower volume when compared to the
gshR deficient mutant. The accumulation of gamma-glutamyl-cysteine was also
higher in L. sanfranciscensis sourdoughs when compared to doughs fermented with
the gshR mutant strain. The accumulation of reduced glutathione in L.
sanfranciscensis bread did not enhance the saltiness of bread.
PMID- 28502177
TI - Leveraging Colloidal Aggregation for Drug-Rich Nanoparticle Formulations.
AB - While limited drug loading continues to be problematic for chemotherapeutics
formulated in nanoparticles, we found that we could take advantage of colloidal
drug aggregation to achieve high loading when combined with polymeric excipients.
We demonstrate this approach with two drugs, fulvestrant and pentyl-PABC
doxazolidine (PPD; a prodrug of doxazolidine, which is a DNA cross-linking
anthracycline), and two polymers, polysorbate 80 (UP80) and poly(d,l-lactide-co-2
methyl-2-carboxytrimethylene carbonate)-graft-poly(ethylene glycol) (PLAC-PEG; a
custom-synthesized, self-assembling amphiphilic polymer). In both systems, drug
loaded nanoparticles had diameters < 200 nm and were stable for up to two days in
buffered saline solution and for up to 24 h in serum-containing media at 37
degrees C. While colloidal drug aggregates alone are typically unstable in saline
and serum-containing media, we attribute the colloid stability observed herein to
the polymeric excipients and consequent decreased protein adsorption. We expect
this strategy of polymer-stabilized colloidal drug aggregates to be broadly
applicable in delivery formulations.
PMID- 28502179
TI - Self-Propelled Motion of Monodisperse Underwater Oil Droplets Formed by a
Microfluidic Device.
AB - We evaluated the speed profile of self-propelled underwater oil droplets
comprising a hydrophobic aldehyde derivative in terms of their diameter and the
surrounding surfactant concentration using a microfluidic device. We found that
the speed of the oil droplets is dependent on not only the surfactant
concentration but also the droplet size in a certain range of the surfactant
concentration. This tendency is interpreted in terms of combination of the oil
and surfactant affording spontaneous emulsification in addition to the Marangoni
effect.
PMID- 28502178
TI - Diverted Total Synthesis of Carolacton-Inspired Analogs Yields Three Distinct
Phenotypes in Streptococcus mutans Biofilms.
AB - The oral microbiome is a dynamic environment inhabited by both commensals and
pathogens. Among these is Streptococcus mutans, the causative agent of dental
caries, the most prevalent childhood disease. Carolacton has remarkably specific
activity against S. mutans, causing acid-mediated cell death during biofilm
formation; however, its complex structure limits its utility. Herein, we report
the diverted total synthesis and biological evaluation of a rationally designed
library of simplified analogs that unveiled three unique biofilm phenotypes
further validating the role of natural product synthesis in the discovery of new
biological phenomena.
PMID- 28502180
TI - Metal Nanoparticle Growth within Clay-Polymer Nacre-Inspired Materials for
Improved Catalysis and Plasmonic Detection in Complex Biofluids.
AB - Recent studies have shown that layered silicate clays can be used to form a nacre
like bioinspired layered structure with various polymer fillers, leading to
composite films with good material strength, gas-barrier properties, and high
loading capacity. We go one step further by in situ growing metal nanoparticles
in nacre-like layered films based on layered silicate clays, which can be used
for applications in plasmonic sensing and catalysis. The degree of anisotropy of
the nanoparticles grown in the film can be controlled by adjusting the ratio of
clay to polymer or gold to clay and reducing agent concentration, as well as
silver overgrowth, which greatly enhances the surface enhanced Raman scattering
activity of the composite. We show the performance of the films for SERS
detection of bacterial quorum sensing molecules in culture medium, and catalytic
properties are demonstrated through the reduction of 4-nitroaniline. These films
serve as the first example of seedless, in situ nanoparticle growth within nacre
mimetic materials, and open the path to basic research on the influence of
different building blocks and polymeric mortars on nanoparticle morphology and
distribution, as well as applications in catalysis, sensing, and antimicrobial
surfaces using such materials.
PMID- 28502181
TI - Rapid Nanogram Scale Screening Method of Microarrays to Evaluate Drug-Polymer
Blends Using High-Throughput Printing Technology.
AB - A miniaturized, high-throughput assay was optimized to screen polymer-drug solid
dispersions using a 2-D Inkjet printer. By simply printing nanoliter amounts of
polymer and drug solutions onto an inert surface, drug/polymer microdots of
tunable composition were produced in an easily addressable microarray format. The
amount of material printed for each dried spot ranged from 25 ng to 650 ng. These
arrays were used to assess the stability of drug/polymer dispersions with respect
to recrystallization, using polarized light microscopy. One array with a panel of
6 drugs formulated at different ratios with a poly(vinylpyrrolidone-vinyl
acetate) (PVPVA) copolymer was developed to estimate a possible bulk (gram-scale)
approximation threshold from the final printed nanoamount of formulation. Another
array was printed at a fixed final amount of material to establish a literature
comparison of one drug formulated with different commercial polymers for
validation. This new approach may offer significant efficiency in pharmaceutical
formulation screening, with each experiment in the nanomicro-array format
requiring from 3 up to 6 orders of magnitude lower amounts of sample than
conventional screening methods.
PMID- 28502182
TI - Isotope-Edited Infrared Spectroscopy for Efficient Discrimination between
Pharmaceutical Salts and Cocrystals.
AB - Isotope-edited infrared spectroscopy using carboxylic acids selectively labeled
with 13C is proposed herein for the efficient discrimination of pharmaceutical
salts and cocrystals, whereby proton-transfer probe vibrations are highlighted by
isotope shifts. This new technique can accurately discriminate even a confusing
salt from a cocrystal for the traditional method, highlighting the diagnostic
peaks. In addition, the established technique also provided the OH in-plane
bending vibrations corresponding to intermolecular hydrogen bonding at the
carbonyl oxygens of the cocrystals. The technique will accelerate the
discrimination, which is a critical process in cocrystal development.
PMID- 28502183
TI - Fabrication and Microscopic and Spectroscopic Characterization of Planar,
Bimetallic, Micro- and Nanopatterned Surfaces.
AB - Micropatterns and nanopatterns of gold embedded in silver and titanium embedded
in gold have been prepared by combining either photolithography or electron-beam
lithography with a glue-free template-stripping procedure. The obtained patterned
surfaces have been topographically characterized using atomic force microscopy
and scanning electron microscopy, showing a very low root-mean-square roughness
(<0.5 nm), high coplanarity between the two metals (maximum height difference ~ 2
nm), and topographical continuity at the bimetallic interface. Spectroscopic
characterization using X-ray photoelectron spectroscopy (XPS), time-of-flight
secondary-ion mass spectrometry (ToF-SIMS), and Auger electron spectroscopy (AES)
has shown a sharp chemical contrast between the two metals at the interface for
titanium patterns embedded in gold, whereas diffusion of silver into gold was
observed for gold patterns embedded in silver. Surface flatness combined with a
high chemical contrast makes the obtained surfaces suitable for applications
involving functionalization with molecules by orthogonal adsorption chemistries
or for instrumental calibration. The latter possibility has been tested by
determining the image sharpness and the analyzed area on circular patterns of
different sizes for each of the spectroscopic techniques applied for
characterization.This is the first study in which the analyzed area has been
determined using XPS and AES on a flat surface, and the first example of a method
for determining the analyzed area using ToF-SIMS.
PMID- 28502185
TI - Characteristics, Management, and Results of Out-of-Hospital Cardiac Arrest (OHCA)
With or Without ST-Segment Elevation Myocardial Infarction (STEMI).
PMID- 28502184
TI - Promoting community malaria control in rural Myanmar through an active community
participation program using the participatory learning approach.
AB - INTRODUCTION: Malaria is prevalent in more than 80% of townships in Myanmar. The
National Malaria Control Programme (NMCP) has been implementing community-based
malaria control programs nationwide. However, these programs are mostly developed
and directed by health authorities, while communities are passively involved.
This study aimed to increase community participation in malaria control and
promote community malaria control knowledge and practice in rural Myanmar.
METHODS: A community-based study, which employed a mixed method approach,
collecting data quantitatively and qualitatively, was conducted in two rural
villages. The study implemented an active community participation program (ACPP)
using the participatory learning approach in a village (ACPP village) but only
routine malaria control was given in another village (non-ACPP village). All
households with 142 and 96 household representatives from ACPP and non-ACPP
villages participated in baseline and endline surveys. The ACPP was evaluated by
process and outcome indicators. A spider gram analysis using five process
indicators was applied to evaluate the process of the ACPP. Community
participation status in malaria control activities and level of community malaria
knowledge and practice were determined as outcomes of the ACPP. RESULTS: The
spider gram analysis showed that three indicators (needs assessment and planning,
leadership and resource mobilization) gained a score of 4, the organization
indicator a score of 5 and the management and evaluation indicator a score of 3.
The outcome indicators of the program at 6 months showed that the community
participation in malaria control activities in the ACPP village had significantly
increased (6.9% to 49.3%) (p<0.001). The program promoted community
malaria control knowledge and practice in the ACPP village. The mean scores of
knowledge, perception, preventive behavior and treatment-seeking behavior were
increased significantly, from 3.0 to 5.9 (p<0.001), 20.1 to 21.0
(p<0.001), 3.4 to 4.2 (p<0.001) and 3.1 to 5.6 (p<0.001),
respectively. However, no significant change of outcome indicators was found in
the non-ACPP village. CONCLUSIONS: The ACPP implemented by community volunteers
using the participatory learning approach was feasible in community-based malaria
control. This study suggests several features in the ACPP model that may be
useful strategies for the implementation of the current NMCP programs in similar
rural settings; however, the effect of the ACPP over a longer period to ascertain
the impact of such community participation has yet to be further studied.
PMID- 28502187
TI - Impaired ventilatory efficiency after closure of atrial or ventricular septal
defect.
AB - OBJECTIVES: Atrial and ventricular septal defects are the most common congenital
heart defects and the closing procedures share important similarities. Generally,
the postoperative outcome is considered benign, but there is growing concern
regarding late ventilatory function. Therefore, the aim of this review was to
describe the ventilatory function in patients with open as well as percutaneously
or surgically closed atrial and ventricular septal defects. METHODS: We performed
a search protocol based on the "Preferred Reporting Items for Systematic Reviews
and Meta-Analyses" (PRISMA) guidelines. A data collection form was specifically
developed and data were extracted from the included studies by a primary reviewer
and cross-checked by the secondary reviewer. RESULTS: We found an increasing
evidence of late impairment in ventilatory efficiency, and despite that
ventilatory function is commonly normal at rest, abnormalities were disclosed
during exercise. There are indices that surgical closure plays an important role.
DISCUSSION: Atrial septal defect and ventricular septal defect patients have
persisting, long-term impairment in ventilatory efficiency during exercise.
Although the pathogenesis behind this finding may be multifactorial, there are
indices that the surgical procedure may play an important role. Nevertheless, the
literature is this field is sparse, and additional studies are needed.
PMID- 28502186
TI - Effectiveness of dydrogesterone, 17-OH progesterone and micronized progesterone
in prevention of preterm birth in women with a short cervix.
AB - OBJECTIVE: To compare the efficacy of dydrogesterone, 17-OH progesterone (17OHP)
and oral or vaginal micronized progesterone with cerclage for the prevention of
preterm birth in women with a short cervix. METHODS: The study included 95 women
with singleton gestation and cervical length (CL) <= 25 mm. Among these, 35 women
were asymptomatic at 15-24 weeks and 60 had symptoms of threatened late
miscarriage (LM) or preterm delivery (PD) at 15-32 weeks. Patients were
randomized to receive dydrogesterone, 17OHP or oral/vaginal micronized
progesterone; after one week of therapy 15 women underwent cerclage. RESULTS:
Efficacy of vaginal progesterone (VP) for the prevention of preterm birth reached
94.1%. In asymptomatic women pregnancy outcomes were comparable to cerclage. In
women with threatened LM/PD, combination therapy with VP, indomethacin and
treatment of bacterial vaginosis (BV) with the subsequent use VP until 36 weeks
together with CL monitoring significantly decreased the rate of preterm birth (RR
0.01; 0.0001-0.24) and low birth weight (LBW) (RR 0.04; 0.01-0.96). CL increase
during the first week of treatment with a subsequent plateau phase indicated
treatment efficacy. Dydrogesterone, 17OHP, and micronized oral progesterone (OP)
were associated with PD in 91.7% of women. CONCLUSIONS: Combination management
strategy including VP significantly benefits pregnancy outcomes in women with a
short cervix compared with cerclage. Dydrogesterone, 17OHP, and OP were not found
to be efficacious.
PMID- 28502188
TI - Surgical site infection after cesarean delivery: incidence and risk factors at a
US academic institution.
AB - PURPOSE: To identify the rate of surgical site infection (SSI) after Cesarean
delivery (CD) and determine risk factors predictive for infection at a large
academic institution. METHODS: This was a retrospective cohort study in women
undergoing CD during 2013. SSIs were defined by Centers for Disease Control (CDC)
criteria. Chi square and t-tests were used for bivariate analysis and
multivariate logistic regression was used to identify SSI risk factors. RESULTS:
In 2419 patients, the rate of SSI was 5.5% (n = 133) with cellulitis in 4.9% (n =
118), deep incisional infection in 0.6% (n = 15) and intra-abdominal infection in
0.3% (n = 7). On multivariate analysis, SSI was higher among CD for labor arrest
(OR 2.4; 95%CI 1.6-3.5; p <.001). Preterm labor (OR 2.8; 95%CI 1.3-6.0; p = .01)
and general anesthesia (OR 4.4; 95%CI 2.0-9.8; p = .003) were predictive for SSI.
Increasing BMI (OR 1.1; 95%CI 1.05-1.09; p = .02), asthma (OR 1.9; 95%CI 1.1-3.2;
p = .02) and smoking (OR 1.9; 95%CI 1.1-3.2; p = .02) were associated with
increased SSI. CONCLUSIONS: Several patient and surgical variables are associated
with increased rate of SSI after CD. Identification of risk factors for SSI after
CD is important for targeted implementation of quality improvement measures and
infection control interventions.
PMID- 28502190
TI - Two rare risk factors for post-partum haemorrhage: a case report of a carrier of
severe haemophilia A with a uterine arteriovenous malformation.
PMID- 28502189
TI - Long-term outcomes of infliximab treatment and predictors of response in 195
patients with ulcerative colitis: a hospital-based cohort study from Korea.
AB - BACKGROUND: Large-scale studies regarding the long-term efficacy of infliximab
(IFX) treatment in non-Caucasian patients with ulcerative colitis (UC) are
lacking. STUDY: We analyzed the long-term outcomes of IFX in 195 Korean UC
patients who received scheduled IFX treatments at Asan Medical Center. IFX
failure was defined as IFX discontinuation due to colectomy or non-response to
IFX, and additionally UC-related hospitalization or a need for rescue
corticosteroids during the course of IFX. RESULTS: Between December 2006 and
October 2016, a total of 3101 infusions of IFX were administered to 195 patients
over a median period of 21 months. At the end of the follow-up, 86 patients
(44.1%) were still receiving IFX without failure. IFX was stopped in 73 (37.4%)
patients due to colectomy (23 patients, 11.8%), non-response to IFX (35 patients,
17.9%) or other reasons such as adverse events or patients' preferences (15
patients, 7.7%). An additional 36 (18.5%) patients experienced IFX failure during
follow-up due to a need for rescue corticosteroids (13 patients, 6.7%), UC
related hospitalization (8 patients, 4.1%), or both (15 patients, 7.7%). The
survival free of IFX failure was 58.1% at 1 year, 50.7% at 3 years and 44.8% at 5
years. In a multivariate regression analysis, cytomegalovirus colitis within 3
months before IFX initiation was a predictor of IFX failure (hazard ratio 1.57;
95% confidence interval 1.04-2.37; p = .032). CONCLUSIONS: The long-term efficacy
of IFX in a large, real-life cohort of Korean UC patients appears to be
comparable to that in previously published Western studies.
PMID- 28502191
TI - A novel mutation in ALS2 associated with severe and progressive infantile onset
of spastic paralysis.
AB - Infantile onset ascending spastic paralysis (IAHSP) is a type of recessively
inherited spastic paraplegia. We investigated the clinical and genetic cause of a
recessively inherited disorder in two siblings manifesting severe spasticity in
the lower limbs which hindered their gait. A novel homozygous nonsense mutation
c.1918 C > T (p.Arg640*) was identified after whole-exome sequencing within ALS2
in the DNA of both patients. The obligate carriers were heterozygous for the
mutation and other unaffected members were homozygous for the wild type allele.
The variant was absent from 100 control chromosomes and all public databases.
This report extends the allelic heterogeneity of ALS2 mutations and emphasizes
the importance of genetic testing for diagnosis of pediatric disorders.
PMID- 28502192
TI - Short and long-term outcomes of Streptococcus pyogenes pneumonia managed in the
intensive care unit.
PMID- 28502194
TI - Spontaneous lumbar spinal subdural hematoma: a case report.
AB - Spinal subdural hematoma (SSDH) is an uncommon disease causing acute onset of
spinal disorder. Several causes of SSDH have been reported, but reports of
spontaneous occurrence of SSDH are limited.
PMID- 28502193
TI - Early-onset obesity and food restriction alter hepatocyte metabolism in adult
Wistar rats.
AB - CONTEXT: Caloric restriction (CR) is suggested for overweight control. OBJECTIVE:
Systemic and liver glucose metabolism in the reduced-litter (RL) rat model under
30% CR was investigated. MATERIALS AND METHODS: Newborn litters were organised in
control (G9); RL with free diet (G3L); and RL with CR (G3R). Assessments were
made at the age of 90 d. RESULTS: Higher liver glycogen content and changes in
systemic glucose handling were found in the RL groups. Hepatocyte glucose
metabolism was similar in groups G9 and G3L, but basal glucose production and
glycogenolysis were higher, while gluconeogenesis and basal glycolysis were lower
in the G3R. Urea production was lower in the RL groups. DISCUSSION: The altered
glucose handling of the RL adult rats was not reversed by moderate (30%) CR.
Hepatocyte glucose and nitrogen metabolism were changed by both early overfeeding
and current feeding conditions. CONCLUSIONS: RL and CR alter systemic and liver
glucose metabolism.
PMID- 28502195
TI - Increase of resistance to fluoroquinolone and retained susceptibility to
macrolides of Campylobacter isolates in Croatia.
PMID- 28502196
TI - Pendulum and modified pendulum appliances for maxillary molar distalization in
Class II malocclusion - a systematic review.
AB - OBJECTIVE: The main purpose of the present systematic review was to evaluate the
quantitative effects of the pendulum appliance and modified pendulum appliances
for maxillary molar distalization in Class II malocclusion. MATERIALS AND
METHODS: Our systematic search included MEDLINE, EMBASE, CINAHL, PsychINFO,
Scopus and key journals and review articles; the date of the last search was 30
January 2017. We graded the methodological quality of the studies by means of the
Quality Assessment Tool for Quantitative Studies, developed for the Effective
Public Health Practice Project (EPHPP). RESULTS: In total, 203 studies were
identified for screening, and 25 studies were eligible. The quality assessment
rated four (16%) of the study as being of strong quality and 21 (84%) of these
studies as being of moderate quality. The pendulum appliances showed mean molar
distalization of 2-6.4 mm, distal tipping of molars from 6.67 degrees to 14.50
degrees and anchorage loss with mean premolar and incisor mesial movement of
1.63-3.6 mm and 0.9-6.5 mm, respectively. The bone anchored pendulum appliances
(BAPAs) showed mean molar distalization of 4.8-6.4 mm, distal tipping of molars
from 9 degrees to 11.3 degrees and mean premolar distalization of 2.7-5.4 mm.
CONCLUSIONS: Pendulum and modified pendulum appliances are effective in molar
distalization. Pendulum appliance with K-loop modification, implant supported
pendulum appliance and BAPA significantly reduced anchorage loss of the anterior
teeth and distal tipping of the molar teeth.
PMID- 28502198
TI - Prevalence of dentin hypersensitivity among the residents of Xi'an city, China.
AB - OBJECTIVE: To investigate the prevalence and intra-oral distribution of dentine
hypersensitivity (DH) and to evaluate the related risk factors. MATERIAL AND
METHODS: A total of 1320 subjects, aged between 20 and 69 years old, were
selected from six communities in the urban areas of Xi'an, China. The data were
collected by conducting individual interviews using a standard questionnaire;
then, the clinical examination was performed for patients who reported about the
discomforts they felt in their teeth when subjected to chemical, mechanical and
thermal stimuli. Dentine hypersensitivity (DH) was diagnosed by a subject short,
sharp pain in response to a blast of cold air from a triple syringe. RESULTS:
While replying to the questionnaire, 445 subjects reported about signs of
discomfort in the teeth. DH was diagnosed in 336 persons by clinic examination.
Thus, the overall prevalence of DH was 33.7% in the questionnaire and 25.5% in
the intraoral test. The prevalence of DH was higher in females (33.8%) than in
males (22.2%). Furthermore, we found that the prevalence of DH was highest in the
age group of 50-59 years (39.3%). The most common initiation factors were acid
(37.7%) followed by cold stimuli (35.8%). In general, most subjects with
sensitive teeth had a higher educational background. CONCLUSIONS: The prevalence
of DH was 25.5% in the population of Xi'an City in China. More emphasis should
give to middle-aged and old females while planning oral health intervention
campaigns. In addition, premolars and cervical surfaces should be examined for
the prevention of DH.
PMID- 28502197
TI - Effect of maternal age on spontaneous abortion during the first trimester in
Northeast China.
AB - OBJECTIVE: We aimed to determine the relationship between fetal chromosomal
abnormalities and maternal age among spontaneous first trimester abortions in
women in Northeast China. METHODS: We evaluated 497 chorionic villi samples from
patients with a history of spontaneous abortion during the first trimester. We
divided the samples into five groups according to the maternal age: <25, 25-29,
30-34, 35-39, and >=40 years. We identified chromosomal abnormalities by
fluorescence in situ hybridization. RESULTS: Among the 497 chorionic samples of
spontaneous abortion, 180 (36.22%) had fetal chromosomal abnormalities. Patients
aged >=40 years had a significantly higher percentage (60.61%) of fetal
chromosomal abnormalities compared with the other groups. More women in the >=40
and 35- to 39-year groups had a history of three consecutive miscarriages and 10
kinds of abnormalities. The most frequent aneuploidy was trisomy 22, followed by
trisomy 16. CONCLUSIONS: These results revealed that the kinds of fetal
abnormalities, numbers of abortions, and chromosomal abnormality rates increased
with increasing maternal age. The most common trisomy types in spontaneous
abortions were closely related to maternal age. We hypothesize whether the larger
probability of chromosomal abnormalities is due to increased mutation rate with
maternal age, or due to a worse in-utero conditions.
PMID- 28502199
TI - Ceramide lipid-based nanosuspension for enhanced delivery of docetaxel with
synergistic antitumor efficiency.
AB - Ceramide (CE), a bioactive lipid with tumor suppression, has been widely used as
a drug carrier and enhancer for cancer therapy. CE-based combination therapy was
prone to be attractive in cancer therapy. In our previous study, the combination
of CE and docetaxel (DTX) was proved to be an effective strategy for cancer
therapy. To further improve the antitumor efficiency of DTX, the CE lipid-based
nanosuspensions (LNS) was prepared for the delivery of DTX to exhibit synergistic
therapeutic effect. The enhanced delivery and synergistic therapeutic effect of
DTX-loaded CE-LNS (CE + DTX-LNS) were evaluated. CE + DTX-LNS exhibited spherical
or ellipsoidal shape, uniform particle size distribution (108.1 +/- 3.8 nm),
sustained release characteristics and good stability in vitro. Notably, CE + DTX
LNS could effectively co-localize CE and DTX into same tumor cell and
subsequently play synergistic cell damage effect compared with CE-LNS + DTX-LNS
(p < 0.05). The in vivo fluorescence imaging results showed that CE + DTX-LNS
could effectively prolong the in vivo circulation time and enhance the
accumulation in tumor sites. Moreover, the antitumor efficacy of CE + DTX-LNS
observed in B16 murine melanoma model was 93.94 +/- 2.77%, significantly higher
than that of CE-LNS, DTX-LNS, Duopafei(r) (p < 0.01) and CE-LNS + DTX-LNS (p <
0.05), respectively, demonstrating that co-delivery of CE and DTX into same tumor
cell was the basis for enhanced synergistic therapeutic effect. Furthermore,
histological examination of Blank-LNS showed no visible tissue toxicity compared
to normal saline. Consequently, CE-LNS could effectively delivery DTX and CE +
DTX-LNS exhibit synergistic inhibition of tumor growth due to the co-localization
of CE and DTX. CE-LNS hold great potential to be an appropriate carrier for CE
based combination chemotherapy.
PMID- 28502200
TI - Foetal premature atrial contractions during the second and third trimester are
not associated with foetal breathing.
AB - Foetal premature atrial contractions (PACs) are the most commonly encountered and
also the most benign foetal arrhythmia. A retrospective cohort study was
conducted with the objective to assess whether the presence of foetal breathing
was associated with the presence of foetal PACs. A further objective was to
evaluate whether this association would affect neonatal outcomes at a high volume
referral centre. The diagnosis of PACs was based on the observation of a
premature atrial contraction followed by a ventricular contraction on ultrasound
myocardial M-mode. Trained ultrasonographers documented in the ultrasound report
whether or not foetal breathing was present with PACs. 91 exams were identified,
which included 75 individual pregnancies. Six women were identified who had
foetal PACs associated with foetal breathing on ultrasound evaluation. Foetuses
with PACs did not differ between the associated breathing and no-associated
breathing groups with respect to maternal age, parity, mode of delivery,
gestational age at delivery or birthweight. This study reaffirms that isolated
PACs are a benign finding. Furthermore, it adds to the pool of literature on
foetal PACs in that it is not associated with abnormal pregnancy outcomes
regardless of the presence or absence of foetal breathing. Impact statement *
What is already known on this subjectSince foetal breathing can effect Doppler
ultrasound assessment of the foetal cardiovascular system, it is reasonable to
consider that it may impact conditions such as foetal arrhythmias. * What the
results of this study addFoetal breathing does not impact on the presence of
premature atrial contractions. * What the implications are of these findings for
clinical practice and/or further researchFoetal breathing is not associated with
the finding of foetal premature atrial contractions.
PMID- 28502201
TI - Prediction of chorioamnionitis in cases of intraamniotic infection by ureaplasma
urealyticum in women with very preterm premature rupture of membranes or preterm
labour.
AB - OBJECTIVES: First, to determinate the frequency of chorioamnionitis and funisitis
in cases of intramniotic detection of Ureaplasma urealyticum. Second, to assess
the predictive capability of some biological markers in the amniotic fluid of
these women to predict histological inflammation. SUBJECTS AND METHODS: We
prospectively studied 20 cases of women with premature rupture of membranes or
preterm labour (PROM) or preterm labour and intraamniotic detection of Ureaplasma
urealyticum. Gestational age at admission was 26.74 +/- 2.53 weeks. Amniotic
fluid concentrations of IL18, IL 2, IL4, IL6, IL10, IL12, TNF-alpha, IFN-g, and
MMP-8 were measured by the Multiplex method. Amniotic fluid glucose and leukocyte
count were also measured by standard methods. Placental detailed histological
studies were performed. Student's t-test, forward stepwise conditional binary
logistic regression analysis and ROC curves were used. RESULTS: Histological
chorioamnionitis was present in 45% of cases (9/20) and funisitis just in 15%
(3/20). Interleukins 6, 8, 12, MMP-8, and leukocyte count were significantly
elevated in cases of histological inflammation, defined as choriamnionitis or
chorioamniotis + funisitis (p = .007, .03, .01, .03, .03, respectively) while
glucose was decreased (p = .04). Binary logistic regression for the prediction of
inflammation showed a high predictive value (R2 = .66, p = .002) including in the
equation only the IL6 value. CONCLUSIONS: A significant percentage of cases with
intraamniotic detection of Ureaplasma urealyticum shows no pathological signs of
histological inflammation. Concentration of Interleukin 6 in amniotic fluid can
be useful for the diagnosis of subclinical chorioamnionitis in these cases.
PMID- 28502204
TI - Alu insertion polymorphisms in the African Sahel and the origin of Fulani
pastoralists.
AB - BACKGROUND: The origin of Western African pastoralism, represented today by the
Fulani nomads, has been a highly debated issue for the past decades, and has not
yet been conclusively resolved. AIM: This study focused on Alu polymorphisms in
sedentary and nomadic populations across the African Sahel to investigate
patterns of diversity that can complement the existing results and contribute to
resolving issues concerning the origin of West African pastoralism. SUBJECTS AND
METHODS: A new dataset of 21 Alu biallelic markers covering a substantial part of
the African Sahel has been analysed jointly with several published North African
populations. RESULTS: Interestingly, with regard to Alu variation, the
relationship of Fulani pastoralists to North Africans is not as evident as was
earlier revealed by studies of uniparental loci such as mtDNA and NRY. Alu
insertions point rather to an affinity of Fulani pastoralists to Eastern Africans
also leading a pastoral lifestyle. CONCLUSIONS: It is suggested that contemporary
Fulani pastoralists might be descendants of an ancestral Eastern African
population that, while crossing the Sahara in the Holocene, admixed slightly with
a population of Eurasian (as evidenced by uniparental polymorphisms) ancestry. It
seems that, in the Fulani pastoralists, Alu elements reflect more ancient genetic
relationships than do uniparental genetic systems.
PMID- 28502202
TI - Cooking processes increase bioactive compounds in organic and conventional green
beans.
AB - The influence of cooking methods on chlorophyl, carotenoids, polyamines,
polyphenols contents and antioxidant capacity were analyzed in organic and
conventional green beans. The initial raw material had a higher content of
chlorophyl and total phenolics in conventional green beans, whereas organic
cultive favored flavonoid content and antioxidant capacity. Polyamines and
carotenoids were similar for the two crop systems. After the cooking process,
carotenoids (beta-carotene, lutein and zeaxanthin) increased. Microwave heating
favored the enhancement of some polar compounds, whereas pressure cooking favored
carotenoids. When we used the estimation of the radical scavenging activity by
electron spin resonance (ESR) spectroscopy, a reduction of the DPPH radical
signal in the presence of green bean extracts was observed, regardless of the
mode of cultivation. The highest reduction of the ESR signal ocurred for
microwave cooking in organic and conventional green beans, indicating a higher
availability of antioxidants with this type of heat treatment.
PMID- 28502203
TI - Chewing gum improves postoperative recovery of gastrointestinal function after
cesarean delivery: a systematic review and meta-analysis of randomized trials.
AB - OBJECTIVE: To examine whether chewing gum hastens the return of gastrointestinal
function after a cesarean delivery. METHODS: All randomized controlled trials
comparing the use of chewing gum in the immediate postoperative recovery period
(i.e. intervention group) with a control group were included in the meta
analysis. The primary outcome was the time to first flatus in hours. Meta
analysis was performed using the random effects model of DerSimonian and Laird,
to produce summary treatment effects in terms of mean difference (MD) or relative
risk (RR) with 95% confidence interval (CI). RESULTS: Seventeen trials, including
3041 women, were analyzed. Trials were of moderate to low quality with different
inclusion criteria. In most of the included trials chewing gum was given right
after delivery, three times a day for 30 min each and until the first flatus.
Women who were randomized to the chewing gum group had a significantly lower mean
time to first flatus (MD - 6.49 h, 95%CI -8.65 to -4.33), to first bowel sounds
(MD - 8.48 h, 95%CI -9.04 to -7.92), less duration of stay (MD - 0.39 days, 95%CI
-0.78 to -0.18), lower time to first feces (MD - 9.57 h, 95% CI -10.28 to 8.87)
and to the first feeling of hunger (MD - 2.89 h, 95%CI -4.93 to -0.85), less
number of episodes of nausea or vomiting (RR 0.33, 95%CI 0.12 to 0.87), less
incidence of ileus (RR 0.39, 95%CI 0.19 to 0.80) and significantly higher
satisfaction. CONCLUSIONS: Gum chewing starting right after cesarean delivery
three times a day for about 30 min until the first flatus is associated with
early recovery of bowel motility. As this is a simple, generally inexpensive
intervention, providers should consider implementing cesarean postoperative care
with gum chewing.
PMID- 28502205
TI - Role of mean platelet volume and ischemia modified albumin in evaluation of
oxidative stress and its association with postnatal complications in infants of
diabetic mothers.
AB - Gestational diabetes mellitus (GDM) is accompanied by increased oxidative stress,
causing many complications to pregnant women and their newborns. We aimed to
determine cord blood levels of mean platelet volume (MPV) and ischemia modified
albumin (IMA) as a reflection of oxidative stress in babies born to mothers
suffering from GDM. Eighty pregnant women were enrolled in the study. They were
divided into two groups: 40 with GDM and 40 healthy matched controls. Each group
included twenty giving birth by normal vaginal delivery (NVD) and twenty by
cesarean section (C.S). The MPV and the IMA levels were measured. Complete
physical examination of babies was done at birth and follow up at age of one
week. Comparison between infants of diabetic mothers and of healthy mothers
showed statistically significant difference in the levels of MPV (p < .001) and
IMA (p = .001). Also, there was a statistically significant difference in MPV (p
< .001) and IMA (p = .005) between diabetic females who gave birth by NVD and
C.S. ROC curve analysis showed that IMA and MPV variables were related to the
postnatal outcomes. MPV and IMA are useful markers of the potential oxidative
stress in infants of diabetic mothers and of postnatal complications.
PMID- 28502206
TI - DNA barcoding and phylogenetic analysis of five ascidians (Phlebobranchia)
distributed in Gulf of Mannar, India.
AB - DNA barcoding has played a significant role in biodiversity assessment as well as
its conservation. This technique involves sequencing of mitochondrial marker gene
including a short COI gene, known as barcode gene. It has proved its efficiency
in identifying several species and resolving the limitations incurred during
identification through conventional taxonomy. This study involves the use of DNA
barcoding of ascidian species belonging to order Phlebobranchia. A total of 14
individuals, covering two families, three genera and five species, were barcoded.
COI gene sequences of all the five species were deposited for the first time in
NCBI as well as BOLD. The NJ tree revealed identical phylogenetic relationship
among the individuals collected from three different stations. Mean Kimura 2
parameter (K2P) distances within-species, genus, family and order were 0.08%,
6.69%, 9.49% and 18.58%, respectively. This result concludes that COI gene
sequencing is the efficient tool in identifying ascidians of the order
Phlebobranchia. We report for the first time the COI gene sequences of four
species of ascidians studied.
PMID- 28502207
TI - Symptoms in the masticatory system and related quality of life in prospective
orthognathic patients.
AB - OBJECTIVE: The aim of this study was to investigate the relation between
orthognathic patients' self-reported symptoms in the head and neck region and
their quality of life (QoL). MATERIAL AND METHODS: Participants included were
consecutive patients (n = 50) referred to the assessment of orthognathic
treatment need and voluntary first-year university students (n = 29). All
participants filled in the Orthognathic Quality of Life Questionnaire (OQLQ) and
a structured diary created by the authors. The median values of Orthognathic
Quality of Life (OQOL) sum and subscores, satisfaction with oral function and
number of awakenings were compared between patients and controls. Further,
correlations between the OQOL sum and subscores, satisfaction with oral function
and number of awakenings were analyzed. RESULTS: Patients reported significantly
more symptoms (p = .013) and woke up significantly more often than the controls
(p = .032). Their OQOL sum scores were significantly higher (indicating a lower
OQOL) (p = .001), and they were significantly less satisfied with their oral
function than the controls (p < .001). Among the awakened and not-rested
patients, the most commonly reported symptoms were pain in the head and/or neck
region and fatigue and/or stiffness in the jaws. CONCLUSIONS: Experiences of pain
and discomfort have a significant impact on patients' OQOL and well-being.
PMID- 28502208
TI - [The prognostic role of extremely high levels of the B-type natriuretic
prohormone with regard to the in-hospital mortality of patients hospitalized for
heart failure].
AB - INTRODUCTION: Patients hospitalized for heart failure have a very high in
hospital as well as one-year mortality. Natriuretic peptides play both a
diagnostic and a prognostic role in this disease. Changes of natriuretic peptide
levels in response to therapy are a well-known prognostic marker. Regarding in
hospital mortality, however, little is known about the prognostic value of
extremely high levels of natriuretic peptides measured on admission. AIM: To
decide whether extremely high levels of B-type natriuretic peptide have a
prognostic value with regard to in-hospital mortality. METHOD: NT-proBNP levels
on admission and in-hospital mortality were extracted retrospectively from the
data of patients treated with heart failure in the cardiology department of the
Hospital of St. John of God in Budapest. We separately analyzed the data of
patients hospitalized for heart failure in 2015 with extremely high initial NT
proBNP levels. The cut-off value in this regard was 10 000 ng/l. We also analyzed
the comorbidities of these patients. RESULTS: The median NT-proBNP level of those
patients who survived beyond the index hospital stay in the last 10 years was
4842 ng/l, whereas the median NT-proBNP level of those 182 patients who died
during their hospital stay was 10 688 ng/l (p<0.001). In the year 2015, we
treated 118 patients with an NT-proBNP level above 10 000 ng/l. Thirteen of these
patients died, which means that their in-hospital mortality exceeded 10%. In
comparison, the in-hospital mortality of all heart failure patients was 5.8%. The
difference of median NT-proBNP levels of surviving versus deceased patients in
this group with extremely high NT-proBNP levels was no longer significant (17 080
ng/l vs. 19 152 ng/l). CONCLUSIONS: Patients with an NT-proBNP level of >10 000
ng/l on admission have a significantly higher in-hospital mortality. The
difference of NT-proBNP levels of surviving versus deceased patients in the group
with admission NT-proBNP levels >10 000 ng/l is no longer significant. We could
not identify any etiological factors that would explain these extremely high NT
proBNP levels or the excess in-hospital mortality. Orv Hetil. 2017; 158(20): 779
782.
PMID- 28502209
TI - [Detection of West Nile virus in human samples: follow-up studies during the 2015
seasonal period].
AB - INTRODUCTION: West Nile virus, a mosquito-borne viral zoonosis is responsible for
human infections in Hungary. Laboratory diagnosis is based on serological tests,
however the application of molecular methods has been appreciated. AIM: The aim
of the study was to investigate blood, cerebrospinal-fluid and urine samples of
acutely ill patients and to follow-up PCR positive cases to ascertain the length
of virus excretion. METHOD: Clinical specimens were examined by indirect
immunofluorescent, haemagglutination-inhibition, two PCR tests and Sanger
sequencing. Virus isolation in case of two patients was successful. RESULTS: A
follow-up study could be carried out in case of 5 patients. Viral nucleic acid
was detectable in urine even for several weeks after symptom onset and viral RNA
was present at higher concentration compared with other samples. CONCLUSIONS: PCR
analysis of urine could provide useful epidemiological and diagnostic
information. Therefore, it is recommended to collect urine samples in order to
supplement the serological diagnosis. Orv Hetil. 2017; 158(20): 791-796.
PMID- 28502210
TI - [Esophageal complications of gastroesophageal reflux disease: consequences or
defensive reactions?]
AB - Gastroesophageal reflux disease affects more than 10% of the adult population.
Most patients can be effectively treated with lifestyle changes and adequate acid
reducing therapy. However, about 10% of the patients remain symptomatic despite
treatment and severe complications may develop. Interestingly, some of these
complications seem to be a sort of defensive mechanism that may either alleviate
the patient's symptoms or prevent developing further complications. In Barrett's
esophagus, which can be unambigously considered as a complication of
gastroesophageal reflux disease, reflux symptoms ruining the quality of life may
significantly improve, since the metaplastic Barrett epithelium is much more
resistent to gastric acid, than the normal epithelial lining of the esophagus.
Furthermore, the motility disorders (hypertensive lower esophageal sphincter,
achalasia, cricopharyngeal achalasia) and structural changes (Schatzki's ring,
esophageal stricture, subglottic trachea stenosis), which develop as a
complication of reflux may help to prevent aspiration that can cause new
complaints and may lead to further complications. Orv Hetil. 2017; 158(20): 763
769.
PMID- 28502212
TI - [Trends in antidiabetic treatment prescribed for patients with type 2 diabetes in
Hungary between 2001 and 2014 - results from the database analysis of the
National Health Insurance Fund].
AB - In the last couple of years, significant developments in antidiabetic treatment
have influenced the pharmacological treatment of type 2 diabetes mellitus (T2DM).
The aim of this study was to analyze the changes in prescribing patterns of
glucose-lowering drugs for T2DM patients in Hungary between 2001 and 2014. The
number of patients with newly diagnosed T2DM decreased from 75,700 (2001) to
33,700 (2014), while prevalent T2DM cases continuously increased and plateaued in
2014 with a number of registered patients of 727,000. Sulfonylurea-monotherapy
decreased from 64% to 35% while metformin-monotherapy increased from 19% to 42%
in this period. The most frequently used drug at first treatment initiation was
metformin (66%) and sulfonylurea (16%) as monotherapy in 2014. DPP4-inhibitors
were newly administered in 20,362 cases while GLP1-mimetics were newly used by
4,996 patients in 2014. Five years later after initiating sulfonylurea therapy
between 2010 and 2014, metformin was more frequently used as second drug (39%)
than sulfonylurea in patients with previous metformin treatment (22.9%). The
prescribing patterns of glucose-lowering drugs have changed over time in
accordance with new guidelines. Further changes in prescribing habits can be
expected in the near future. Orv Hetil. 2017; 158(20): 770-778.
PMID- 28502213
TI - [Analysis of mortality and its predictors in patients with contralateral hip
fracture after femoral neck fracture].
AB - INTRODUCTION: There is a high mortality with not well understood risk factors
after the second hip fracture. AIM: Analysis of the 30- and 365-day mortality and
its risk factors in patients with contralateral hip fracture. METHOD: Patients
with contralateral hip fracture between 01 Jan 2000 and 31 Dec 2008 were
identified among those who suffered their primary hip fracture in Hungary in
2000. Risk factors as age, sex, concomitant and chronic diseases, type of
fracture and surgery, surgical complications, day of admission were analyzed by
logistic and Cox regression as well as Kaplan-Meier analysis. RESULTS: There were
312 eligible patients identified with 8.3 % mortality rate at 30 and with 38,4%
at 365 days respectively. Significant risk factors for the 30 day mortality were
intertrochanteric type of fracture (OR: 4.722; HR: 4.129) and non operative
management (OR: 7.357; HR: 6.317) while for the 365 day mortality those were
older age (OR:1.070; HR:1.050) and type of surgery (OR: 0.450). CONCLUSION: Age,
type of fracture and type of surgery proved to be risk factors. There is a need
to identify further risk factors in order to develop an efficacious prevention
strategy for the reduction of the mortality after the second hip fractures. Orv
Hetil. 2017; 158(20): 783-790.
PMID- 28502214
TI - Giving Our Daughters What We Never Received: African American Mothers Discussing
Sexual Health With Their Preadolescent Daughters.
AB - African American girls experience disparate rates of pregnancy and acquisition of
sexually transmitted infections, including human immunodeficiency virus, when
compared to their non-Hispanic White counterparts. Among African American girls,
current pregnancy rates are equal to the national crisis levels of teen pregnancy
reported in 1990. This qualitative elicitation study was conducted to gain
insight into the ways in which African American mothers and their daughters,
between the ages of 9 and 14, communicate about sexual health. Early sexual
health communication between mothers and daughters is known to enhance the sexual
health outcomes of girls. A series of four focus groups and three in-depth
interviews were conducted between July and September 2014. The theory of planned
behavior was the organizing framework. Theoretical constructs that guided this
study were attitudes, perceived behavioral control, and subjective norms. Results
showed that what African American women share with their daughters about sexual
health stems from their personal faith, values, and experiences. Findings from
this study can inform interventions to provide support for this understudied
population. Moreover, there are implications for health-care providers,
particularly school nurses, who are in an ideal position to help increase
mothers' self-efficacy to engage in sexual health conversations with their young
daughters.
PMID- 28502215
TI - In response to C Walshe, 'The state of play'.
PMID- 28502216
TI - A retrospective analysis of postoperative recurrence of septated chronic subdural
haematoma: endoscopic surgery versus burr hole craniotomy.
AB - OBJECTIVE: To identify the factors associated with Septated chronic subdural
haematoma (sCSDH) recurrence and to compare the advantages and disadvantages of
burr hole craniotomy (BHC) and endoscopic surgery (ES) with respect to preventing
sCSDH recurrence. METHODS: A total of 76 consecutive patients with sCSDH
underwent BHC or ES in our institution. Their clinical data were retrospectively
analysed to identify the factors associated with sCSDH recurrence and to evaluate
the effectiveness of BHC and ES with respect to preventing sCSDH recurrence.
RESULTS: There were no significant differences in gender, age, Markwalder grade,
side of haematoma, preoperative mid-line shifts, intervals, clinical features or
medical histories between the two groups. Bilateral sCSDH was the only factor
that significantly influenced the sCSDH recurrence rate (RR) (p = 0.001). Male
gender, age >= 60 years, poor Markwalder grade, preoperative mid-line shifts <=10
mm, postoperative mid-line shifts >10 mm, neovessels, intervals <=20 days and
medical histories tended to be associated with sCSDH recurrence. The RRs in the
BHC and ES groups were 13.7 and 8.7%, respectively. ES eliminated more factors
associated with recurrence than BHC; however, ES required more surgery time (p <
0.001) and more medical consumption (p < 0.001) than BHC. CONCLUSIONS: Bilateral
sCSDH exerted the most significant influence on the sCSDH RR. There was no
difference between ES and BHC with respect to decreasing the sCSDH RR. However,
BHC is a more efficient procedure than ES, as it required less surgery time and
less medical consumption than ES.
PMID- 28502217
TI - Hippocampal low-frequency stimulation inhibits afterdischarge and increases GABA
(A) receptor expression in amygdala-kindled pharmacoresistant epileptic rats.
AB - OBJECTIVE: The purpose of the present study was to observe the effects of
hippocampal low-frequency stimulation (Hip-LFS) on amygdala afterdischarge and
GABA (A) receptor expression in pharmacoresistant epileptic (PRE) rats. METHODS:
A total of 110 healthy adult male Wistar rats were used to generate a model of
epilepsy by chronic stimulation of the amygdala. Sixteen PRE rats were selected
from 70 amygdala-kindled rats by testing their response to Phenytoin and
Phenobarbital, and they were randomly assigned to a pharmacoresistant stimulation
group (PRS group, 8 rats) or a pharmacoresistant control group (PRC group, 8
rats). A stimulation electrode was implanted into the hippocampus of all of the
rats. Hip-LFS was administered twice per day in the PRS group for two weeks.
Simultaneously, amygdala stimulus-induced seizures and afterdischarge were
recorded. After the hippocampal stimulation was terminated, the brain tissues
were obtained to determine the GABA (A) receptors by a method of
immumohistochemistry and a real-time polymerase chain reaction. RESULTS: The
stages and duration of the amygdala stimulus-induced epileptic seizures were
decreased in the PRS group. The afterdischarge threshold was increased and the
duration as well as the afterdischarge frequency was decreased. Simultaneously,
the GABA (A) expression was significantly increased in the PRS group.
CONCLUSIONS: Hip-LFS may inhibit amygdala stimulus-induced epileptic seizures and
up-regulate GABA (A) receptor expression in PRE rats. The antiepileptic effects
of hippocampal stimulation may be partly achieved by increasing the GABA (A)
receptor.
PMID- 28502219
TI - Towards an ethics for telehealth.
AB - Over the last two decades, a public rationale for the implementation of
telehealth has emerged at the interplay of specialised literature and political
orientations. Despite the lack of consistent findings on the magnitude of its
benefits, telehealth is nowadays presented as a worthy solution both for patients
and healthcare institutions. Far from denying the potential advantages of
telehealth, the main objective of this work is to provide a critical assessment
on the spread of the remote services as a vector of positive transformation of
contemporary health systems. For pursuing this objective, the EU agenda for the
promotion of telehealth will be retraced, and the main evidences alleged to
sustain the implementation of remote care services will be assessed. Furthermore,
it will be evaluated the attempt made by the European Commission to establish an
ethical framework for guiding the use of telehealth in daily practice, and a
roadmap of the most relevant legal and ethical issues posed by the spread of
telehealth will be traced. In the conclusions, it will be argued that the radical
transformations induced by this form of technological innovation call on to a
new, ad hoc ethics through which critically evaluate benefits and implications of
telehealth services, with a view to keep high the standard of healthcare against
the economic interests of private stakeholders and ICTs' vendors.
PMID- 28502218
TI - Recommendations to reduce inequalities for LGBT people facing advanced illness:
ACCESSCare national qualitative interview study.
AB - BACKGROUND: Lesbian, gay, bisexual and/or trans (LGBT) people have higher risk of
certain life-limiting illnesses and unmet needs in advanced illness and
bereavement. ACCESSCare is the first national study to examine in depth the
experiences of LGBT people facing advanced illness. AIM: To explore health-care
experiences of LGBT people facing advanced illness to elicit views regarding
sharing identity (sexual orientation/gender history), accessing services,
discrimination/exclusion and best-practice examples. DESIGN: Semi-structured in
depth qualitative interviews analysed using thematic analysis.
SETTING/PARTICIPANTS: In total, 40 LGBT people from across the United Kingdom
facing advanced illness: cancer ( n = 21), non-cancer ( n = 16) and both a cancer
and a non-cancer conditions ( n = 3). RESULTS: In total, five main themes
emerged: (1) person-centred care needs that may require additional/different
consideration for LGBT people (including different social support structures and
additional legal concerns), (2) service level or interactional (created in the
consultation) barriers/stressors (including heteronormative assumptions and
homophobic/transphobic behaviours), (3) invisible barriers/stressors (including
the historical context of pathology/criminalisation, fears and experiences of
discrimination) and (4) service level or interactional facilitators (including
acknowledging and including partners in critical discussions). These all shape
(5) individuals' preferences for disclosing identity. Prior experiences of
discrimination or violence, in response to disclosure, were carried into future
care interactions and heightened with the frailty of advanced illness.
CONCLUSION: Despite recent legislative change, experiences of discrimination and
exclusion in health care persist for LGBT people. Ten recommendations, for health
care professionals and services/institutions, are made from the data. These are
simple, low cost and offer potential gains in access to, and outcomes of, care
for LGBT people.
PMID- 28502220
TI - Dynamic assessment of visual neglect: The Mobility Assessment Course as a
diagnostic tool.
AB - INTRODUCTION: Visual neglect is a frequent disorder following stroke and is often
diagnosed by neuropsychological assessment. However, paper-and-pencil tasks have
low predictive value as they lack sensitivity to capture neglect in complex,
dynamic situations, such as activities of daily living. Aims of the current study
were to assess the feasibility of the Mobility Assessment Course (MAC), a visual
search multitask, to assess neglect, and its relation with existing neglect
tasks. METHOD: Stroke patients admitted for inpatient rehabilitation and healthy
controls were tested with the MAC in different corridors. Participants had to
move through a corridor, finding and reporting 24 targets attached to the walls.
In addition, the shape cancellation, line bisection, and Catherine Bergego Scale
(CBS) were used in order to compare the MAC with existing diagnostic tools for
neglect. RESULTS: Administering the MAC was feasible, as 112 of 113 patients
completed the MAC with a median duration of 4.09 min. Depending on the corridor
where the assessment took place, in 88.5-93.3% of assessments all targets were
visible. The number of omissions (total and contralesional) and the asymmetry
score (contralesional-ipsilesional omissions) on the MAC as well as collisions
and corrections, were higher for patients with neglect than for those without
neglect. Depending on the neglect task used, 4.0-18.6% of patients without
neglect on neuropsychological tasks or the CBS showed neglect on the MAC. Vice
versa, 17.2-29.3% of patients who showed neglect at neuropsychological assessment
or the CBS did not do so on the MAC. Finally, a moderate to strong positive
relation was seen between neglect at neuropsychological assessment, the CBS, and
the MAC. CONCLUSIONS: The MAC is an ecological task in which both quantitative
and qualitative data on neglect can be collected. In order to assess the presence
of neglect and neglect severity in a dynamic way, the MAC could be administered
in conjunction with neuropsychological assessment.
PMID- 28502221
TI - Reliability of mandibular movement assessments depending on TMD.
AB - OBJECTIVE: This study determines the effect of temporomandibular disorders (TMD)
on the reliability of mandibular movement assessments. METHODS: The vertical and
horizontal jaw movements, as well as overjet and overbite, were measured twice in
56 consecutively recruited adult subjects with TMD according to the RDC/TMD and
29 controls without TMD diagnosis by experienced dentists utilizing a millimeter
ruler. The reliability was determined by intraclass correlation coefficient
(ICC). RESULTS: Neither statistically nor clinically relevant differences in the
repeatability between both subgroups could be detected (all p >= 0.077). The
mouth opening and overjet proved an excellent reliability (ICC 0.85-0.92).
Overbite and laterotrusion showed good to excellent reliable results (ICC 0.74
0.82). The second measurement of the vertical jaw movement resulted in
systematically higher values (p < 0.003). DISCUSSION: The assessment of the
mandibular movement with a millimeter ruler is a reliable procedure irrespective
of TMD. To decrease the variances in the mouth opening measurements, the patient
should be asked beforehand to practice this movement.
PMID- 28502222
TI - Understanding pain physiology and its application to person with intellectual
disability.
AB - The issue of pain warrants attention as, by virtue of having an intellectual
disability, a person may have associated medical or physical conditions and
associated factors increasing their risk of pain disorders. People with
intellectual disability experiencing pain need to be provided with the best
possible care. The focus of this article is on the exploration of pain:
physiology and types; manifestations and responses in the context of intellectual
disability in order to promote effective, knowledgeable assessment and management
of pain for this client group. Pain is a subjective, complex, physiological and
psychological phenomenon that can be acute or chronic and may be classified
according to its cause. Within the experience of pain, the concept of total pain
describes the physical, psychological, social and spiritual factors that
influence the experience of pain.
PMID- 28502223
TI - Investigation of angiogenesis genes with anterior cruciate ligament rupture risk
in a South African population.
AB - The angiogenesis-signalling pathway is a physiological response after mechanical
loading to promote matrix remodelling and thereby maintain tissue homeostasis.
Studies have shown increased expression of angiogenic molecules in response to
loading and in ruptured ligaments. Recently, polymorphisms within the vascular
endothelial growth factor A (VEGFA) and kinase insert-domain receptor (KDR) genes
were associated with risk of anterior cruciate ligament (ACL) ruptures and
Achilles tendinopathy in Caucasian study groups. A case-control genetic
association study was conducted on 100 controls and 98 participants with
surgically-diagnosed ACL ruptures; of which 51 participants reported non-contact
mechanism of injury (NON). All participants were genotyped for five functional
polymorphisms: VEGFA (rs699947, rs1570360, rs2010963) and KDR (rs2071559,
rs1870377). Haplotypes were inferred. In the male participants, the KDR rs2071559
AG genotype was significantly over-represented (P = 0.048, OR: 1.90, 95% CI: 1.00
3.59) in the controls. Furthermore, the GG genotype was significantly under
represented in the male controls compared to the male ACL group (P = 0.018, OR:
2.77, 95% CI: 1.17-6.55) and the male NON subgroup (P = 0.013, OR: 3.26, 95% CI:
1.24-8.58). Haplotype analysis implicated the KDR gene in all participants and in
male participants separately. Collectively, these results implicate the
angiogenesis-signalling pathway as a potentially key biological pathway
contributing to ACL injury susceptibility.
PMID- 28502224
TI - Diagnosis and treatment of paediatric tuberculosis: An insight review.
AB - Tuberculosis (TB) is a major public health problem, invading all age groups world
wide. It is an opportunistic infection affecting the individuals alone or with co
infections. Childhood TB is a neglected aspect and a significant health problem
in epidemic areas. It constitutes more than 20% of TB incidence. Pediatric TB
exists in the shadow of adult TB. The clinicians concentrate on pulmonary
manifestation of TB, whereas it is a major problem in both pulmonary and extra
pulmonary infections. The rate of infection with this disease is mostly
associated with poverty, social disruption and human immunodeficiency virus (HIV)
infection. The diagnosis of extra-pulmonary TB (EPTB) is more difficult than
pulmonary TB (PTB). Delayed diagnosis and executive treatment contribute to
increase in the mortality rate in endemic areas. This article provides the
evidence-based simple and safe screening method, indicating rapid, highly
sensitive and specific diagnostic tests for pulmonary and EPTB in children. The
most important aspect of treatment is the correct course of anti-tubercular
drugs. This review serves the purpose of quick reference for microbiologists,
epidemiologists, academicians, students and researchers. It provides guidance
regarding early diagnosis and treatment accuracy of pediatric TB.
PMID- 28502225
TI - Genomics of lactic acid bacteria: Current status and potential applications.
AB - Lactic acid bacteria (LAB) are widely used for the production of a variety of
foods and feed raw materials where they contribute to flavor and texture of the
fermented products. In addition, specific LAB strains are considered as probiotic
due to their health-promoting effects in consumers. Recently, the genome
sequencing of LAB is booming and the increased amount of published genomics data
brings unprecedented opportunity for us to reveal the important traits of LAB.
This review describes the recent progress on LAB genomics and special emphasis is
placed on understanding the industry-related physiological features based on
genomics analysis. Moreover, strategies to engineer metabolic capacity and stress
tolerance of LAB with improved industrial performance are also discussed.
PMID- 28502226
TI - Stronger interference from distractors in the right hemifield during visual
search.
AB - The orientation-bias hypothesis states that there is a bias to attend to the
right visual hemifield (RVF) when there is spatial competition between stimuli in
the left and right hemifield [Pollmann, S. (1996). A pop-out induced extinction
like phenomenon in neurologically intact subjects. Neuropsychologia, 34(5), 413
425. doi: 10.1016/0028-3932(95)00125-5 ]. In support of this hypothesis, stronger
interference was reported for RVF distractors with contralateral targets. In
contrast, previous studies using rapid serial visual presentation (RSVP) found
stronger interference from distractors in the left visual hemifield (LVF). We
used the additional singleton paradigm to test whether this discrepancy was due
to the different distractor features that were employed (colour vs. orientation).
Interference from the colour distractor with contralateral targets was larger in
the RVF than in the LVF. However, the asymmetrical interference disappeared when
observers had to search for an inconspicuous colour target instead of the
inconspicuous shape target. We suggest that the LVF orienting-bias is limited to
situations where search is driven by bottom-up saliency (singleton search)
instead of top-down search goals (feature search). In contrast, analysis of the
literature suggests the opposite for the LVF bias in RSVP tasks. Thus, the
attentional asymmetry may depend on whether the task involves temporal or spatial
competition, and whether search is based on bottom-up or top-down signals.
PMID- 28502227
TI - Malaria and severe anemia over eight years at Gambo Rural Hospital, southern
Ethiopia.
AB - Evolution of incident malaria and frequency of anemia were analyzed over eight
years in a rural hospital in southern Ethiopia. Capillary blood samples were
tested for hemoglobin concentration, and in some instances for malaria parasites,
at Gambo Rural General Hospital between January 2007 and September 2014, and the
results recorded. Main demographic data were also recorded in subjects with
Plasmodium sp. infections. Of a total of 54,493 blood samples taken from 45,096
different patients, 21,723 (39.9%) samples from 19,173 (42.5%) patients were
tested for malaria parasites. Malaria was diagnosed in 825 (3.79%, 95% CI 3.55%,
4.06%) instances (58.3% P. vivax and 41.7% P. falciparum; one episode in 575
patients and two episodes in 125 patients). A sustained decrease in yearly
incidence of malaria was observed between 2011 (6.1%) and 2014 (2.4%) (p < 0.01).
Of all the malaria patients, those with hemoglobin levels less than 8 g/dL, were
younger compared to those with levels of 8 g/dL or more (median age of 5 years
vs. 18 years; p < 0.01) and more commonly infected with P. falciparum (57.1% vs.
34.8%; p < 0.001). In multivariate analysis, severe anemia (hemoglobin <8 g/dL)
in the context of anemia was associated with P falciparum infection (adjusted odd
ratio [OR] 2.48, 95% confidence interval [CI] 1.68, 3.65) and younger age (OR
1.06, 95% CI 1.04, 1.07).
PMID- 28502228
TI - The toxic effects of polychlorinated biphenyl (Aroclor 1242) on Tm3 Leydig cells.
AB - Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental
contaminants that disrupt endocrine function in biological systems, especially in
the male reproductive system. Previous studies on the reproductive toxicity of
PCBs have focused on the impairment of spermatogenesis, disruption of
steroidogenesis, decreased sperm number, and infertility. Aroclor 1242 is a
commercial mixture with an average of 42% chlorine by weight. The purpose of the
present study was to elucidate the hazardous effects of Aroclor 1242 on Leydig
cells through an evaluation of cell viability, lipid peroxidation, hydroxyl
radicals, H2O2 production, antioxidant enzymes, and steroidogenic enzymes. Leydig
cells were exposed to Aroclor 1242 for 24 h under basal and luteinizing hormone
stimulated conditions at different concentrations (ranging from 10-16 M to 10-6
M). After incubation, Leydig cells were measured for cell viability, lipid
peroxidation, reactive oxygen species (hydroxyl radical and H2O2), antioxidant
enzymes (catalase, superoxide dismutase, glutathione peroxidase, and glutathione
S-transferase), and steroidogenic enzymes (3beta-hydroxysteroid dehydrogenase
[HSD] and 17beta-HSD). The results showed that cell viability was reduced only at
Aroclor 1242 concentrations of 10-6 M and 10-8 M, whereas lipid peroxidation and
reactive oxygen species increased relative to the concentration. Furthermore,
antioxidant systems and steroidogenesis were interrupted to varying degrees,
relative to the concentration. These findings suggest that exposure to Aroclor
1242 at high concentrations may result in detrimental effects to Leydig cell
homeostasis. In addition, Aroclor 1242 may impair steroidogenesis, especially
testosterone biosynthesis, by inhibiting two important steroidogenic enzymes.
PMID- 28502230
TI - The Emerging Genetic-Genomic Era and the Implications for the Holistic Nurse.
PMID- 28502229
TI - Hexavalent chromium induces reactive oxygen species and impairs the antioxidant
power of human erythrocytes and lymphocytes: Decreased metal reducing and free
radical quenching ability of the cells.
AB - The toxicity of hexavalent chromium [Cr(VI)] in biological systems is thought to
be closely associated with the generation of free radicals and reactive oxygen
species. These species are produced when Cr(VI) is reduced to its trivalent form
in the cell. This process results in oxidative stress due to an imbalance between
the detoxifying ability of the cell and the production of free radicals. We have
studied the effect of potassium dichromate (K2Cr2O7), a [Cr(VI)] compound, on the
antioxidant power of human erythrocytes and lymphocytes under in vitro
conditions. Incubation of erythrocytes and lymphocytes with different
concentrations of K2Cr2O7 resulted in a marked dose-dependent decrease in reduced
glutathione and an increase in oxidized glutathione and reactive oxygen species
levels. The antioxidant power of the cells was decreased, as determined by metal
reducing and free radical quenching assays. These results show that [Cr(VI)]
upregulates the generation of reactive oxygen species and, as a consequence, the
cellular antioxidant defences are compromised. The resulting oxidative stress may
contribute to Cr(VI)-induced cellular damage.
PMID- 28502231
TI - Examination of the Use of Healing Touch by Registered Nurses in the Acute Care
Setting.
PMID- 28502232
TI - Exploring the Global Applicability of Holistic Nursing.
PMID- 28502233
TI - Introduction to Guest Editorials.
PMID- 28502234
TI - A gonadotropin-releasing hormone agonist for the prevention of docetaxel-induced
gonadal damage.
AB - This study aimed to evaluate the protective effect of a gonadotropin-releasing
hormone (GnRH) agonist against docetaxel-induced gonadotoxicity in a mouse model.
Forty mice (female B6, 6-8 weeks old, weighing 16-18 g) were divided randomly
into four groups. Groups 1 and 2 were treated with a single intraperitoneal dose
of 0.1 mL normal saline; Groups 3 and 4 received 30 mg/kg docetaxel. Groups 2 and
4 were pre-treated with a subcutaneous injection of 0.3 mg leuprolide acetate, 2
weeks before the administration of docetaxel. The ovaries were removed 6 weeks
after docetaxel or saline injection. Total follicle number decreased in Group 3
compared to Group 1. There was a significant difference between the Groups 3 and
4 in the total follicle number. Many ovarian follicles were stained for Ki-67 in
Groups 1, 2, and 4; however, in Group 3, only a small number were stained and
destruction of the ovarian structure was observed. There was no
immunohistochemistry staining with gamma-H2AX in Groups 1, 2, and 4. However,
gamma-H2AX staining of the primordial follicles was observed in Group 3. GnRH
agonists may protect ovarian follicles from docetaxel-induced ovarian damage
considering the total follicle number, follicle proliferation, and double-strand
DNA breaks. Impact statement Protection of the ovarian reserve and prevention of
infertility are the primary quality of life issues in young cancer patients. In
this study, ovarian suppression by gonadotropin-releasing hormone agonists
protected ovarian follicles from docetaxel-induced ovarian damage considering the
total follicle number, follicle proliferation, and double-strand DNA break. The
findings of our study will provide useful information for fertility preservation
in women with cancer, undergoing chemotherapy with docetaxel.
PMID- 28502235
TI - Molecular analysis and genetic diversity of Aedes albopictus (Diptera, Culicidae)
from China.
AB - Aedes albopictus is one of the most invasive species, which can carry Dengue
virus, Yellow fever virus and more than twenty arboviruses. Based on
mitochondrial gene cytochrome c oxidase I (COI) and samples collected from 17
populations, we investigated the molecular character and genetic diversity of Ae.
albopictus from China. Altogether, 25 haplotypes were detected, including 10
shared haplotypes and 15 private haplotypes. H1 was the dominant haplotype, which
is widely distributed in 13 populations. Tajima'D value of most populations was
significantly negative, demonstrating that populations experienced rapid range
expansion recently. Most haplotypes clustered together both in phylogenetic and
median-joining network analysis without clear phylogeographic patterns. However,
neutrality tests revealed shallow divergences among Hainan and Guangxi with other
populations (0.15599 <= FST <= 0.75858), which probably due to interrupted gene
flow, caused by geographical isolations. In conclusion, Ae. albopictus
populations showed low genetic diversity in China.
PMID- 28502236
TI - Family Presence in the Adult ICU During Bedside Procedures.
AB - PURPOSE: To understand perspectives of family members of adult patients admitted
to the medical-surgical intensive care unit (ICU) regarding their presence during
procedures. METHODS: Respondents completed a questionnaire about procedures the
patient had undergone, their desire to be present, and their experience.
Procedures of interest were endotracheal intubation; chest compressions; vascular
catheter insertion; and gastric, chest, and rectal tubes. Impact of Events Scale
Revised (IES-R) was completed at the time of questionnaire completion and again 1
month later to evaluate the psychological impact of witnessing a procedure.
RESULTS: Ninety-seven respondents completed the questionnaire on behalf of 72
patients. More than 90% patients had at least 1 procedure. Only 29 (30%) family
members were present for at least 1 procedure, and 44% to 100% wished to be
present. Of the 68 respondents not present for a procedure, 18 (26.5%) wanted to
be present. The IES-R was completed by 52 (95%) of 55 respondents who witnessed
any procedure at time 1 and 28 (51%) of 55 respondents at time 2; mean IES-R
scores were 8.0 and 8.8 ( P = .68), respectively. Only 2 participants had IES-R
>33, signifying the likely presence of posttraumatic stress disorder. CONCLUSION:
Family members wish to be present for ICU procedures, and there are no adverse
psychological effects.
PMID- 28502238
TI - Parotid gland mean dose as a xerostomia predictor in low-dose domains.
AB - PURPOSE: Xerostomia is a common side effect of radiotherapy resulting from
excessive irradiation of salivary glands. Typically, xerostomia is modeled by the
mean dose-response characteristic of parotid glands and prevented by mean dose
constraints to either contralateral or both parotid glands. The aim of this study
was to investigate whether normal tissue complication probability (NTCP) models
based on the mean radiation dose to parotid glands are suitable for the
prediction of xerostomia in a highly conformal low-dose regime of modern
intensity-modulated radiotherapy (IMRT) techniques. MATERIAL AND METHODS: We
present a retrospective analysis of 153 head and neck cancer patients treated
with radiotherapy. The Lyman Kutcher Burman (LKB) model was used to evaluate
predictive power of the parotid gland mean dose with respect to xerostomia at 6
and 12 months after the treatment. The predictive performance of the model was
evaluated by receiver operating characteristic (ROC) curves and precision-recall
(PR) curves. RESULTS: Average mean doses to ipsilateral and contralateral parotid
glands were 25.4 Gy and 18.7 Gy, respectively. QUANTEC constraints were met in
74% of patients. Mild to severe (G1+) xerostomia prevalence at both 6 and 12
months was 67%. Moderate to severe (G2+) xerostomia prevalence at 6 and 12 months
was 20% and 15%, respectively. G1 + xerostomia was predicted reasonably well with
area under the ROC curve ranging from 0.69 to 0.76. The LKB model failed to
provide reliable G2 + xerostomia predictions at both time points. CONCLUSIONS:
Reduction of the mean dose to parotid glands below QUANTEC guidelines resulted in
low G2 + xerostomia rates. In this dose domain, the mean dose models predicted G1
+ xerostomia fairly well, however, failed to recognize patients at risk of G2 +
xerostomia. There is a need for the development of more flexible models able to
capture complexity of dose response in this dose regime.
PMID- 28502237
TI - Investigation of the effective components of the flowers of Trollius chinensis
from the perspectives of intestinal bacterial transformation and intestinal
absorption.
AB - CONTEXT: The flowers of Trollius chinensis Bunge (Ranunculaceae), used for
respiratory tract infections, mainly contain flavonoids, phenolic acids, and
alkaloids; however, the effective components are debatable because of their
unclear in vivo activities. OBJECTIVE: This study investigates the effective
components from the perspectives of biotransformation and absorption. MATERIALS
AND METHODS: Both single person derived- and multiple people-derived intestinal
florae were used to investigate the biotransformation of aqueous extract of the
flowers of T. chinensis (AEOF) at the concentrations of 15.0, 30.0, and 60.0
mg/mL, respectively, for 72 h. Both human colon adenocarcinoma cell line (Caco-2)
monolayers and everted gut sacs were employed to evaluate the intestinal
absorption of the intestinal bacterial transformed AEOF at the concentrations of
10, 20, and 30 mg/mL, respectively, for 180 min. RESULTS: 2"-O-beta-l
Galactopyranosylorientin, orientin, vitexin, quercetin, veratric acid,
proglobeflowery acid, and trolline in AEOF were not transformed by intestinal
bacteria, while isoquercetin and trollioside were completely transformed. The
Papp values of 2"-O-beta-l-galactopyranosylorientin, orientin, and vitexin
calculated based on the experimental data of intestinal absorption were at the
levels of 10-5, whereas those of veratric acid, proglobeflowery acid, and
trolline were at 10-4. The mass ratio of flavonoids to phenolic acids to
alkaloids changed from 16:10:7 to 9:12:8 before and after absorption. DISCUSSION
AND CONCLUSION: The dominant position of flavonoids was replaced by phenolic
acids after absorption. In addition to flavonoids which are usually considered as
the dominant effective ones, phenolic acids and alkaloids should be also very
important for the efficacy of these flowers.
PMID- 28502239
TI - Data versus Spock: lay theories about whether emotion helps or hinders.
AB - The android Data from Star Trek admired human emotion whereas Spock viewed
emotion as irrational and maladaptive. The theory that emotions fulfil adaptive
functions is widely accepted in academic psychology but little is known about
laypeople's theories. The present study assessed the extent to which laypeople
share Data's view of emotion as helpful or Spock's view of emotion as a
hindrance. We also assessed how help and hinder theory endorsement were related
to reasoning, emotion regulation, and well-being. Undergraduates (N = 630)
completed a stressful timed reasoning task and questionnaires that assessed their
theories of emotion, emotion regulation strategies, happiness, and social
support. Overall, participants viewed emotion more as a help than a hindrance.
The more they endorsed the view that emotion helps, the better their reasoning
scores. Endorsing a help theory also predicted the use of reappraisal which, in
turn, predicted greater happiness and social support. In contrast, endorsing the
view that emotion hinders was associated with emotion suppression and less social
support. Thus, people's theories about the functionality of emotion may have
important implications for their reasoning and emotional well-being.
PMID- 28502240
TI - Pediatric Primary Care Providers' Use of Behavioral Health Consultation.
AB - This column describes a qualitative study in which 32 primary care providers
(PCPs) reported barriers to and facilitators of using a behavioral health (BH)
consultation program. Barriers included program incompatibility with
organizational culture, limited exposure to the program, existing access to
referral sources, and negative beliefs about BH consultation. Reported
facilitators included having personal relationships with BH program staff,
exposure to program information, and positive beliefs about BH consultation. PCPs
recommended outreach activities and optimal program features to increase use of
BH consultation.
PMID- 28502241
TI - Competitive Employment Outcomes Among Veterans in VHA Therapeutic and Supported
Employment Services Programs.
AB - OBJECTIVE: The study assessed whether receiving specific types of Veterans Health
Administration (VHA) Therapeutic and Supported Employment Services (TSES) between
fiscal years (FYs) 2006 and 2010 (a time frame that encompasses the Great
Recession) was associated with obtaining competitive employment among veterans
with mental illnesses. METHODS: The sample included 38,199 veterans discharged
from the VHA's TSES program in FY 2006 through FY 2010. On the basis of program
monitoring forms completed by TSES clinicians and workload data, veterans were
classified as having received one main type of employment service: supported
employment (SE), transitional work in the community (TW-community), transitional
work in a Department of Veterans Affairs medical center (TW-VA), incentive
therapy or sheltered workshop (IT/SW), and no main type of employment service.
RESULTS: Compared with veterans who received TW-VA, those who received SE (odds
ratio [OR]=1.25) or TW-community (OR=1.24) were more likely to be competitively
employed (p<.001), and veterans who received IT/SW were less likely (OR=.85)
(p<.001). The predicted probabilities for obtaining competitive employment ranged
from 27.2% (IT/SW) to 34.9% (SE). Odds of achieving competitive employment
(ORs=.60-.97) were significantly lower during the years of the Great Recession
(2007-2009) and in the subsequent year (2010), compared with the year prior
(p<.001 to <.05). CONCLUSIONS: Although rates of competitive employment were
modest across all types of services, community-based employment services were
associated with higher odds of achieving competitive employment, compared with
services based in a medical center. The Great Recession negatively affected the
likelihood of achieving competitive employment, regardless of the employment
service received.
PMID- 28502242
TI - Clinical Decision Making and Mental Health Service Use Among Persons With Severe
Mental Illness Across Europe.
AB - OBJECTIVE: The study explored relationships between preferences for and
experiences of clinical decision making (CDM) with service use among persons with
severe mental illness. METHODS: Data from a prospective observational study in
six European countries were examined. Associations of baseline staff-rated
(N=213) and patient-rated (N=588) preferred and experienced decision making with
service use were examined at baseline by using binomial regressions and at 12
month follow-up by using multilevel models. RESULTS: A preference by patients and
staff for active patient involvement in decision making, rather than shared or
passive decision making, was associated with longer hospital admissions and
higher costs at baseline and with increases in admissions over 12 months
(p=.043). Low patient-rated satisfaction with an experienced clinical decision
was also related to increased costs over the study period (p=.005). CONCLUSIONS:
A preference for shared decision making may reduce health care costs by reducing
inpatient admissions. Patient satisfaction with decisions was a predictor of
costs, and clinicians should maximize patient satisfaction with CDM.
PMID- 28502244
TI - Evaluating the Implementation of Integrated Mental Health Care: A Systematic
Review to Guide the Development of Quality Measures.
AB - OBJECTIVE: Although the effectiveness of integrated mental health care has been
demonstrated, its implementation in real-world settings is highly variable, may
not conform to evidence-based practice, and has rarely been evaluated. Quality
indicators can guide improvements in integrated care implementation. However, the
literature on indicators for this purpose is limited. This article reports
findings from a systematic review of existing measures by which to evaluate
integrated care models in primary care settings. METHODS: Bibliographic databases
and gray literature sources, including academic conference proceedings, were
searched to July 2014. Measures used or proposed to evaluate integrated care
implementation or outcomes were extracted and critically appraised. A qualitative
synthesis was conducted to generate a panel of unique measures and to group these
measures into broad domains and specific dimensions of integrated care program
performance. RESULTS: From 172 literature sources, 1,255 measures were extracted,
which were distilled into 148 unique measures. Existing literature frequently
reports integrated care program effectiveness vis-a-vis evidence-based care
processes and individual clinical outcomes, as well as efficiency (cost
effectiveness) and client satisfaction. No measures of safety of care and few
measures of equitability, accessibility, or timeliness of care were located,
despite the known benefits of integrated care in several of these areas.
CONCLUSIONS: To realize the potential for quality measurement to improve
integrated care implementation, future measures will need to incorporate domains
of quality that are presently unaddressed; microprocesses of care that influence
effectiveness, sustainability, and transferability of models of care; and client
and health care provider perspectives on meaningful measures of quality.
PMID- 28502243
TI - A 60-Week Prospective RCT of a Self-Management Intervention for Individuals With
Serious Mental Illness and Diabetes Mellitus.
AB - OBJECTIVES: A 60-week randomized controlled trial assessed the effects of
targeted training in illness management (TTIM) versus treatment as usual among
200 individuals with serious mental illness and diabetes mellitus. METHODS: The
study used the Clinical Global Impression (CGI), the Montgomery-Asberg Depression
Rating Scale (MADRS), and the Brief Psychiatric Rating Scale (BPRS) to assess
psychiatric symptoms; the Global Assessment of Functioning (GAF) and the Sheehan
Disability Scale (SDS) to assess functioning; the 36-Item Short-Form Health
Survey (SF-36) to assess general health, and serum glycosylated hemoglobin
(HbA1c) to assess diabetes control. RESULTS: Participants' mean+/-SD age was
52.7+/-9.5 years, and 54% were African American. They were diagnosed as having
depression (48%), schizophrenia (25%), and bipolar disorder (28%). At baseline,
depression severity was substantial but psychosis severity was modest. At 60
weeks, there was greater improvement among TTIM participants versus treatment-as
usual recipients on the CGI (p<.001), the MADRS (p=.016), and the GAF (p=.003).
Diabetes knowledge was significantly improved among TTIM participants but not in
the treatment-as-usual group. In post hoc analyses among participants whose HbA1c
levels at baseline met recommendations set by the American Diabetes Association
for persons with high comorbidity (53%), TTIM participants had minimal change in
HbA1c over the 60-week follow-up, whereas HbA1c levels worsened in the treatment
as-usual group. CONCLUSIONS: TTIM was associated with improved psychiatric
symptoms, functioning, and diabetes knowledge compared with treatment as usual.
Among participants with better diabetes control at baseline, TTIM participants
had better diabetes control at 60 weeks compared with recipients of treatment as
usual.
PMID- 28502245
TI - Involuntary Psychiatric Admissions and Development of Psychiatric Services as an
Alternative to Full-Time Hospitalization in France.
AB - OBJECTIVE: The development of alternatives to full-time hospitalization in
psychiatry is limited because consensus about the benefits of such alternatives
is lacking. This study assessed whether the development of such alternatives in
French psychiatric sectors was associated with a reduction in involuntary
inpatient care, taking into account other factors that are potentially associated
with involuntary admission. METHODS: Data on whether a patient had at least one
involuntary full-time admission in 2012 were extracted from the French national
discharge database for psychiatric care. The development of alternatives to full
time hospitalization was estimated as the percentage of human resources allocated
to these alternatives out of all human resources allocated to psychiatry,
measured at the level of the hospital hosting each sector. Other factors
potentially associated with involuntary admission (characteristics of patients,
health care providers, and the environment) were extracted from administrative
databases, and a multilevel logistic model was carried out to account for the
nested structure of the data. RESULTS: Significant variations were observed
between psychiatric sectors in rates of involuntary inpatient admissions. A large
portion of the variation was explained by characteristics of the sectors. A
significant negative association was found between involuntary admissions and the
development of alternatives to full-time hospitalization, after adjustment for
other factors associated with involuntary admissions. CONCLUSIONS: Findings
suggest that the development of alternatives to full-time hospitalization is
beneficial for quality of care, given that it is negatively associated with
involuntary full-time admissions. The reduction of such admissions aligns with
international recommendations for psychiatric care.
PMID- 28502246
TI - Time in Assertive Community Treatment: A Statewide Quality Improvement Initiative
to Reduce Length of Participation.
AB - The investigators describe a New York State initiative to increase flow through
assertive community treatment (ACT) while encouraging transition to less
intensive services. This initiative began as ACT approached full capacity and as
evidence emerged that participants can sustain recovery post-ACT. Comparison of
performance indicators over time showed that time in ACT decreased, turnover rate
increased, and the percentage of ACT participants who met treatment objectives
rose. Also, post-ACT rates of ambulatory behavioral health follow-up increased
while rates of psychiatric inpatient hospitalization decreased. Monitoring
utilization of services while demonstrating positive outcomes has become
increasingly critical as states shift to managed health care.
PMID- 28502247
TI - Assessing the Costs and Benefits of Insuring Psychological Services as Part of
Medicare for Depression in Canada.
AB - OBJECTIVE: The study estimated costs and effects associated with increasing
access to publicly funded psychological services for depression in a public
health care system. METHODS: Discrete event simulation modeled clinical events
(relapse, recovery, hospitalizations, suicide attempts, and suicide), health
service use, and cost outcomes over 40 years in a population with incident
depression. Parameters included epidemiologic and economic data from the
literature and data from a secondary analysis of the 2012 Canadian Community
Health Survey on mental health. Societal costs were measured with the human
capital approach. Analyses estimated the incremental cost-effectiveness ratio
associated with improved access to psychological services among individuals not
receiving adequate mental health care and reporting an unmet need for such care
compared with present use of health services for mental health reasons. RESULTS:
Over 40 years, increased access to mental health services in a simulated
population of adults with incident depression would lead to significantly lower
lifetime prevalence of hospitalizations (27.9% versus 30.2% base case) and
suicide attempts (14.1% versus 14.6%); fewer suicides (184 versus 250); a per
person gain of .17 quality-adjusted life years; and average societal cost savings
of $2,590 CAD per person (range $1,266-$6,320). Publicly funding psychological
services would translate to additional costs of $123,212,872 CAD ($67,709,860
$190,922,732) over 40 years. Savings to society would reach, on average,
$246,997,940 CAD ($120,733,356-$602,713,120). CONCLUSIONS: In Canada, every $1
invested in covering psychological services would yield $2.00 ($1.78 to $3.15) in
savings to society. Covering psychological services as part of Medicare for
individuals with an unmet need for mental health care would pay for itself.
PMID- 28502248
TI - How Do Private Health Plans Manage Specialty Behavioral Health Treatment Entry
and Continuing Care?
AB - OBJECTIVE: This study examined private health plans' arrangements for accessing
and continuing specialty behavioral health treatment in 2010 as federal health
reforms were being implemented. These management practices have historically been
stricter in behavioral health care than in general medical care; however, the
Mental Health Parity and Addiction Equity Act of 2010 required parity in
management policies. METHODS: The data source was a nationally representative
survey of private health plans' behavioral health treatment management approaches
in 2010. Health plan executives were asked about activities for their plan's
three products with highest enrollment (weighted N=8,427, 88% response rate).
RESULTS: Prior authorization for outpatient behavioral health care was rarely
required (4.7% of products), but 75% of products required authorization for
ongoing care and over 90% required prior authorization for other levels of care.
The most common medical necessity criteria were self-developed and American
Society of Addiction Medicine criteria. Nearly all products had formal standards
to limit waiting time for routine and urgent treatment, but almost 30% lacked
such standards for detoxification services. A range of wait time-monitoring
approaches was used. CONCLUSIONS: Health plans used a variety of methods to
influence behavioral health treatment entry and continuing care. Few relied on
prior authorization for outpatient care, but the use of other approaches to
influence, manage, or facilitate access was common. Results provide a baseline
for understanding the current management environment for specialty behavioral
health care. Tracking health plans' approaches over time will be important to
ensure that access to behavioral health care is not prohibitively restrictive.
PMID- 28502249
TI - Psychiatric Mental Health Nursing Advanced Practice Workforce: Capacity to
Address Shortages of Mental Health Professionals.
AB - There is a recognized shortage of mental health professionals licensed to provide
the full scope of mental health services, including assessment, diagnosis, and
prescribing. Psychiatric mental health advanced practice nurses (PMH APNs) have
the education and licensure to provide these services, address provider shortages
and increase access to services. Unfortunately, federal reports and mental health
workforce studies inaccurately depict important characteristics of PMH APNs,
particularly their scope of practice, a situation that creates misunderstanding
and impedes workforce planning. This Open Forum provides an accurate depiction of
the PMH APN workforce, its size, scope of practice, and its capacity to increase
access to mental health services. Also considered are the implications of using
integrated care to increase access to mental health treatment. PMH APNs could
increase the reach of these collaborative care models, which require constructing
interprofessional teams in which each provider practices to the top of his or her
license.
PMID- 28502250
TI - Antiplasmodial dihetarylthioethers target the coenzyme A synthesis pathway in
Plasmodium falciparum erythrocytic stages.
AB - BACKGROUND: Malaria is a widespread infectious disease that threatens a large
proportion of the population in tropical and subtropical areas. Given the
emerging resistance against the current standard anti-malaria chemotherapeutics,
the development of alternative drugs is urgently needed. New anti-malarials
representing chemotypes unrelated to currently used drugs have an increased
potential for displaying novel mechanisms of action and thus exhibit low risk of
cross-resistance against established drugs. RESULTS: Phenotypic screening of a
small library (32 kinase-inhibitor analogs) against Plasmodium falciparum NF54
luc asexual erythrocytic stage parasites identified a diarylthioether
structurally unrelated to registered drugs. Hit expansion led to a series in
which the most potent congener displayed nanomolar antiparasitic activity (IC50 =
39 nM, 3D7 strain). Structure-activity relationship analysis revealed a
thieno[2,3-d]pyrimidine on one side of the thioether linkage as a prerequisite
for antiplasmodial activity. Within the series, the oxazole derivative KuWei173
showed high potency (IC50 = 75 nM; 3D7 strain), good solubility in aqueous
solvents (1.33 mM), and >100-fold selectivity toward human cell lines. Rescue
experiments identified inhibition of the plasmodial coenzyme A synthesis as a
possible mode of action for this compound class. CONCLUSIONS: The class of
antiplasmodial bishetarylthioethers reported here has been shown to interfere
with plasmodial coenzyme A synthesis, a mechanism of action not yet exploited for
registered anti-malarial drugs. The oxazole congener KuWei173 displays double
digit nanomolar antiplasmodial activity, selectivity against human cell lines,
high drug likeness, and thus represents a promising chemical starting point for
further drug development.
PMID- 28502253
TI - PRACTICE OF CONSANGUINITY AND ATTITUDES TOWARDS RISK IN THE PASHTUN POPULATION OF
KHYBER PAKHTUNKHWA, PAKISTAN.
AB - SummaryThis study aimed to investigate the frequency of consanguineous marriages
and level of understanding of consanguinity-associated genetic risks in the
Pashtun population, Pakistan. Information was gathered using a detailed
questionnaire completed by 1500 individuals of both sexes over the 11-month
period between April 2015 and February 2016. The mean inbreeding coefficient of
the respondents was calculated and a five-point response scale was used to assess
their understanding of consanguinity risks. The frequency of consanguineous
marriages in the Pashtun population was found to be 58.3%, with a mean inbreeding
coefficient of 0.0259. Marriage between second cousins was found to be the
dominant marriage type. Level of education was found to be negatively related to
the incidence of consanguineous marriage (p<0.001), and higher consanguinity was
reported among the rural than the urban population (p<0.001). Participants in the
>=25-year age group, those with a higher level of education and those residing in
urban areas exhibited a significantly higher understanding of consanguinity
risks. The overall prevalence of consanguinity in the Pashtun population is high,
demonstrating the need for awareness of its risks in the target population. The
timely dissemination of information on potential health-related risks and the
introduction of genetic counselling in the region would benefit both the
individuals concerned and the community in general.
PMID- 28502251
TI - St John's wort (Hypericum perforatum)-induced psychosis: a case report.
AB - BACKGROUND: St John's wort (Hypericum perforatum) has been known for centuries
for its therapeutic properties and its efficacy as an antidepressant has been
confirmed by a growing body of evidence. During the last two decades it has also
come to prominence with a wider public, due to advertising efforts across Europe
and United States of America. However, its availability without prescription, as
an over-the-counter medication, raises some concern regarding its clinical
management and unsupervised administration to individuals with psychopathological
risks. To date, the evidence available regarding the administration of Hypericum
in people with severe mental health problems is still meager and refers mainly to
affective disorder spectrum or psychotic relapse in people with established
diagnoses. To the best of our knowledge, this is the first report regarding the
onset of psychotic features in a patient presenting with psychotic diathesis.
CASE PRESENTATION: The case discussed in this report is a 25-year-old white man,
not known to the psychiatric services, with a history of brief and self-remitting
drug-induced psychosis and a positive family history of psychotic depression. He
was admitted to hospital due to the onset of florid psychotic symptoms
concomitant with self-administration of Hypericum perforatum. CONCLUSIONS: The
aim of this report is to promote further systematic research, draw the attention
of clinicians to the potential risks of Hypericum precipitating psychosis, and
raise awareness among health professionals to investigate and caution their
patients on the haphazard use of phytotherapeutics such as Hypericum.
PMID- 28502254
TI - Dactylogyrids (Platyhelminthes, Monogenoidea) from the gills of Hoplias
malabaricus (Characiformes: Erythrinidae) from coastal rivers of the Oriental
Amazon Basin: species of Urocleidoides and Constrictoanchoratus n. gen.
AB - Five species of Urocleidoides (one new) and two new species of
Constrictoanchoratus n. gen. are described in this study. All were collected from
the gills of Hoplias malabaricus (Characiformes: Erythrinidae) captured in six
localities of coastal rivers of the north-eastern sector the State of Para
(Oriental Amazon): Urocleidoides brasiliensis Rosim, Mendoza-Franco & Luque,
2011; Urocleidoides bulbophallus n. sp.; Urocleidoides cuiabai Rosim, Mendoza
Franco & Luque, 2011; Urocleidoides eremitus Kritsky, Thatcher & Boeger, 1986;
Urocleidoides malabaricusi Rosim, Mendoza-Franco & Luque, 2011;
Constrictoanchoratus lemmyi n. gen. n. sp.; and Constrictoanchoratus
ptilonophallus n. gen. n. sp. This is the first reported occurrence of the four
previously described species of Urocleidoides parasitizing H. malabaricus from
streams in the Oriental Amazon Basin. The analysis of voucher specimens of U.
eremitus parasitizing the gills of H. malabaricus from the Upper Parana River
floodplain in the limits of States of Parana and Mato Grosso do Sul, Brazil,
indicates that these specimens are members of a new species of Urocleidoides,
described here as Urocleidoides paranae n. sp. Constrictoanchoratus n. gen. is
proposed for the species with a male copulatory organ sclerotized, coiled,
clockwise; ventral anchor with elongate superficial root, inconspicuous deep
root; dorsal anchor with inconspicuous roots, and a constriction at the
intersection between the shaft and the point. The host-parasite diversity
scenario and host specificity of the species of Constrictoanchoratus n. gen. and
Urocleidoides from the gills of H. malabaricus are also discussed in this study.
PMID- 28502252
TI - Differential analysis of mutations in the Jewish population and their
implications for diseases.
AB - Sequencing large cohorts of ethnically homogeneous individuals yields genetic
insights with implications for the entire population rather than a single
individual. In order to evaluate the genetic basis of certain diseases
encountered at high frequency in the Ashkenazi Jewish population (AJP), as well
as to improve variant annotation among the AJP, we examined the entire exome,
focusing on specific genes with known clinical implications in 128 Ashkenazi Jews
and compared these data to other non-Jewish populations (European, African, South
Asian and East Asian). We targeted American College of Medical Genetics
incidental finding recommended genes and the Catalogue of Somatic Mutations in
Cancer (COSMIC) germline cancer-related genes. We identified previously known
disease-causing variants and discovered potentially deleterious variants in known
disease-causing genes that are population specific or substantially more
prevalent in the AJP, such as in the ATP and HGFAC genes associated with
colorectal cancer and pancreatic cancer, respectively. Additionally, we tested
the advantage of utilizing the database of the AJP when assigning pathogenicity
to rare variants of independent whole-exome sequencing data of 49 Ashkenazi Jew
early-onset breast cancer (BC) patients. Importantly, population-based filtering
using our AJP database enabled a reduction in the number of potential causal
variants in the BC cohort by 36%. Taken together, population-specific sequencing
of the AJP offers valuable, clinically applicable information and improves AJP
filter annotation.
PMID- 28502255
TI - A moist edge environment aids the regeneration of traumatic tympanic membrane
perforations.
AB - OBJECTIVE: To review the history of moist therapy used to regenerate traumatic
tympanic membrane perforations. STUDY DESIGN: Literature review. METHODS: The
literature on topical agents used to treat traumatic tympanic membrane
perforations was reviewed, and the advantages and disadvantages of moist therapy
were analysed. RESULTS: A total of 76 studies were included in the analysis.
Topical applications of certain agents (e.g. growth factors, Ofloxacin Otic
Solution, and insulin solutions) to the moist edges of traumatic tympanic
membrane perforations shortened closure times and improved closure rates.
CONCLUSION: Dry tympanic membrane perforation edges may be associated with crust
formation and centrifugal migration, delaying perforation closure. On the
contrary, moist edges inhibit necrosis at the perforation margins, stimulate
proliferation of granulation tissue and aid eardrum healing. Thus, moist
perforation margins upon topical application of solutions of appropriate agents
aid the regeneration of traumatic tympanic membrane perforations.
PMID- 28502256
TI - Survival outcomes following salvage surgery for oropharyngeal squamous cell
carcinoma: systematic review.
AB - BACKGROUND: Recurrent oropharyngeal squamous cell carcinoma causes great
morbidity and mortality. This systematic review analyses survival outcomes
following salvage surgery for recurrent oropharyngeal squamous cell carcinoma.
METHODS: A comprehensive search of various electronic databases was conducted.
Studies included patients with recurrent or residual oropharyngeal squamous cell
carcinoma treated with salvage surgery. Primary outcomes were survival rates
following salvage surgery. Secondary outcomes included time to recurrence,
staging at time of recurrence, post-operative complications, and factors
associated with mortality and recurrence. Methodological appraisal and data
extraction were conducted as per Joanna Briggs Institute methodology. RESULTS:
Eighteen articles were included. The two- and five-year survival rates of the
patients were 52 per cent and 30 per cent respectively. CONCLUSION: Improvements
in treatment modalities for recurrent oropharyngeal squamous cell carcinoma were
associated with improvements in two-year overall survival rates, with minimal
change to five-year overall survival rates. Various factors were identified as
being associated with long-term overall survival, thus assisting clinicians in
patient counselling and selection for salvage surgery.
PMID- 28502257
TI - Physics moves to the provinces: the Siberian physics community and Soviet power,
1917-1940.
AB - The rich tradition of Siberian science and higher education is little known
outside Russian academic circles. Using institutional history, this article
focuses on the founding and pre-war period of the Siberian Physical Technical
Institute, the establishment of its research focus and its first difficult steps
to become a leading centre of R & D in Siberia. Based on archival materials, the
article describes how local and national physicists justified the institute's
creation by demonstrating ties with industry and building on the presence of a
cohort of locally trained physicists, whose numbers were augmented by Leningrad
specialists. The strength of local cadres enabled the institute to navigate civil
war and cultural revolution successfully. Physicists were able to take advantage
of ongoing industrialization campaigns to gain support to create the institute,
although local disputes and economic problems slowed its further development. The
article describes the circulation of scientific, political and philosophical
knowledge between Moscow, Leningrad and the provinces, and the impact of
Bolshevik rule and Stalinism on the Siberian physics enterprise.
PMID- 28502258
TI - Balloon Eustachian tuboplasty treatment of longstanding Eustachian tube
dysfunction.
AB - BACKGROUND: Eustachian tube dysfunction is a poorly defined condition associated
with various symptoms and it can predispose to middle-ear disease. Balloon
dilation Eustachian tuboplasty has been proposed as a treatment for Eustachian
tube dysfunction. OBJECTIVE: To evaluate the subjective and objective outcomes of
balloon dilation Eustachian tuboplasty in patients with recurrent, previously
treated chronic Eustachian tube dysfunction. METHODS: The study was conducted on
11 patients (13 ears) who had undergone previous unsuccessful medical and
surgical treatment. Tympanometry was the primary outcome measure. Secondary
outcome measures included pure tone audiogram assessment and seven-item
Eustachian Tube Dysfunction Questionnaire score. RESULTS: Balloon dilation
Eustachian tuboplasty resulted in significant improvements in 11 patients'
subjective but not objective outcome measures. CONCLUSION: The objective
abnormality and subjective symptoms in Eustachian tube dysfunction may represent
two distinct pathological processes, which may nevertheless influence and
exacerbate each other.
PMID- 28502259
TI - Effects of goldfish (Carassius auratus) population size and body condition on the
transmission of Gyrodactylus kobayashii (Monogenea).
AB - Field surveys indicate that host population size, rather than density, is the
most important determinant of monogenean infection dynamics. To verify this
prediction, epidemic parameters were monitored for 70 days at five host
population sizes held at constant density using a goldfish - Gyrodactylus
kobayashii laboratory model. During the first 20 days, the rate of increase of
prevalence and mean abundance was faster in small host populations. Total mean
prevalence and total mean abundance throughout the experiment were not
significantly affected by host population sizes. Higher transmission rates were
detected in larger host populations. However, there were no significant
differences in effective contact rates among the five host populations on each
sampling day during the first 20 days, implying that contact rates may be
saturated at a sufficiently high host density. These results demonstrate that the
epidemic occurs more quickly in smaller host populations at the beginning of the
experiment. However, the epidemic is independent of the host population size due
to the similar effective contact rates in the five population sizes. Significant
negative influence of the initial body condition (Kn) of uninfected goldfish on
total mean abundance of parasites suggests that susceptibility of hosts is also a
determinant of parasite transmission.
PMID- 28502260
TI - The first study on opportunistic intestinal microsporidiosis in IBD patients
receiving immunosuppressive medications in Iran.
AB - Microsporida are known as opportunistic unicellular organisms and have recently
been reclassified as fungi that have been frequently reported from patients with
congenital and acquired immunity failure disorders, worldwide. However, use of
immunosuppressive medications in inflammatory bowel disease (IBD) patients
significantly decreases overall immunity, and increases their susceptibility to
opportunistic infections. Totally, 71 stool samples were collected from IBD
patients consisted of 69 ulcerative colitis (UC) patients and two Crohn's disease
(CD) patients. All patients had taken immunosuppressive and/or immunomodulator
drugs for at least 3 weeks. DNA was extracted from all stool samples and Nested
PCR was performed using genus-specific primers based on small subunit ribosomal
RNA (SSU rRNA) gene. Fisher's Exact Test was applied to evaluate statistical
association between microsporidia infection and sex, age and types of IBD. Mean
of age +/- s.d., women and men percentage of the attended patients were 36.17 +/-
11.93, 60.6%, and 39.4%, respectively. A 440-bp fragment of SSU rRNA gene
attributed to Enterocytozoon bieneusi was amplified from 12.7% of IBD patients.
No Encephalitozoon DNA was detected in the samples. No microsporidia-positive
sample was found in CD patients. Fisher's Exact Test showed that there was no
statistically significant correlation between intestinal microsporidiosis and
age, sex, and IBD types with P values: 0.389, 1.00, and 1.00, respectively. This
study has shown IBD patients undergoing immunosuppressive/immunomodulators
medications, which may be susceptible to intestinal microsporida infection. E.
bieneusi is the commonest intestinal microsporidan reported from IBD patients.
PMID- 28502261
TI - Profiles of Executive Function Across Children with Distinct Brain Disorders:
Traumatic Brain Injury, Stroke, and Brain Tumor.
AB - OBJECTIVES: This study examined whether children with distinct brain disorders
show different profiles of strengths and weaknesses in executive functions, and
differ from children without brain disorder. METHODS: Participants were children
with traumatic brain injury (N=82; 8-13 years of age), arterial ischemic stroke
(N=36; 6-16 years of age), and brain tumor (N=74; 9-18 years of age), each with a
corresponding matched comparison group consisting of children with orthopedic
injury (N=61), asthma (N=15), and classmates without medical illness (N=68),
respectively. Shifting, inhibition, and working memory were assessed,
respectively, using three Test of Everyday Attention: Children's Version (TEA-Ch)
subtests: Creature Counting, Walk-Don't-Walk, and Code Transmission. Comparison
groups did not differ in TEA-Ch performance and were merged into a single control
group. Profile analysis was used to examine group differences in TEA-Ch subtest
scaled scores after controlling for maternal education and age. RESULTS: As a
whole, children with brain disorder performed more poorly than controls on
measures of executive function. Relative to controls, the three brain injury
groups showed significantly different profiles of executive functions.
Importantly, post hoc tests revealed that performance on TEA-Ch subtests differed
among the brain disorder groups. CONCLUSIONS: Results suggest that different
childhood brain disorders result in distinct patterns of executive function
deficits that differ from children without brain disorder. Implications for
clinical practice and future research are discussed. (JINS, 2017, 23, 529-538).
PMID- 28502263
TI - Infection, specificity and host manipulation of Australapatemon sp. (Trematoda,
Strigeidae) in two sympatric species of leeches (Hirudinea).
AB - Factors that drive parasite specificity and differences in infection dynamics
among alternative host species are important for ecology and evolution of host
parasite interactions, but still often poorly known in natural systems. Here, we
investigated spatiotemporal dynamics of infection, host susceptibility and
parasite-induced changes in host phenotype in a rarely explored host-parasite
system, the Australapatemon sp. trematode infecting two sympatric species of
freshwater leeches, Erpobdella octoculata and Helobdella stagnalis. We show
significant variation in infection abundance between the host species in both
space and time. Using experimental infections, we also show that most of this
variation likely comes from interspecific differences in exposure rather than
susceptibility. Moreover, we demonstrate that the hiding behaviour of E.
octoculata, but not that of H. stagnalis, was impaired by the infection
irrespective of the parasite abundance. This may increase susceptibility of E.
octoculata to predation by the final avian host. We conclude that differences in
patterns of infection and in behavioural alterations among alternative sympatric
host species may arise in narrow spatial scales, which emphasises the importance
of local infection and transmission dynamics for parasite life cycles.
PMID- 28502262
TI - Effects of combined IUGR and prenatal stress on the development of the
hippocampus in a fetal guinea pig model.
AB - Intrauterine growth restriction (IUGR) and maternal stress during pregnancy are
two compromises that negatively impact neurodevelopment and increase the risk of
developing later life neuropsychiatric disorders such as schizophrenia,
depression and behavioural disorders. Neurosteroids, particularly
allopregnanolone, are important in protecting the developing brain and promoting
many essential neurodevelopmental processes. Individually, IUGR and prenatal
stress (PS) reduce myelination and neurogenesis within affected fetal brains,
however less information is available on the combined effects of these two
disorders on the term fetal brain. This study aimed to investigate how IUGR and
PS impairs the neurosteroid pathway when combined using a guinea pig model, and
how these then disrupt the neurodevelopment of the fetus. Uterine artery blood
flow restriction was performed at GA30-35 to induce growth restriction, whilst PS
was induced by exposure of the dam to a strobe light during gestation commencing
GA40 and repeated every 5 days. Exposure in this model caused reductions in
hippocampal CA1 MBP immunostaining of male fetuses in both IUGR alone and IUGR+PS
paradigms but only by IUGR in the subcortical white mater, compared with control
males. Plasma allopregnanolone was reduced by both stressors irrespective of sex,
whereas GFAP or MAP2 expression were not affected by either stressor. Female
neurodevelopment, as assessed by these markers, was unimpeded by these
compromises. The addition of prenatal stress did not further compound these
deficits.
PMID- 28502264
TI - Study of the impact on Salmonella of moving outdoor pigs to fresh land.
AB - Anecdotal evidence has suggested that outdoor-kept pigs show an improvement to
health and productivity after being moved to a new site. This study explores
whether Salmonella occurrence reduced and was sustained after moving to a new
site. Nine farms were followed for a year in which four sampling visits were
completed. The highest detection of Salmonella was from pooled faecal dropping
from pigs, run-off/ pooled water, rodents and wild birds. Descriptive summaries
showed that the prevalence of both all Salmonella and serovars of public health
importance were lower at all visits after the move. Some variability was shown in
results from individual farms, but a year after the move, six farms still
maintained a lower prevalence. A risk factor model showed that the prevalence at
visits 2 and 3 after the move was significantly lower than baseline, after
accounting for a number of significant factors that were included in the model.
These were sample type and seasonality (included as a priori), presence of
coughing in the sampled group and Glasser's disease on the farm, and the use of
tent or kennel accommodation. This finding provides important evidence that more
frequent site moves may help reduce Salmonella prevalence in outdoor herds.
PMID- 28502265
TI - Psychological autopsy study comparing suicide decedents, suicide ideators, and
propensity score matched controls: results from the study to assess risk and
resilience in service members (Army STARRS).
AB - BACKGROUND: The suicide rate has increased significantly among US Army soldiers
over the past decade. Here we report the first results from a large psychological
autopsy study using two control groups designed to reveal risk factors for
suicide death among soldiers beyond known sociodemographic factors and the
presence of suicide ideation. METHODS: Informants were next-of-kin and Army
supervisors for: 135 suicide cases, 137 control soldiers propensity-score-matched
on known sociodemographic risk factors for suicide and Army history variables,
and 118 control soldiers who reported suicide ideation in the past year. RESULTS:
Results revealed that most (79.3%) soldiers who died by suicide have a prior
mental disorder; mental disorders in the prior 30-days were especially strong
risk factors for suicide death. Approximately half of suicide decedents tell
someone that they are considering suicide. Virtually all of the risk factors
identified in this study differed between suicide cases and propensity-score
matched controls, but did not significantly differ between suicide cases and
suicide ideators. The most striking difference between suicides and ideators was
the presence in the former of an internalizing disorder (especially depression)
and multi-morbidity (i.e. 3+ disorders) in the past 30 days. CONCLUSIONS: Most
soldiers who die by suicide have identifiable mental disorders shortly before
their death and tell others about their suicidal thinking, suggesting that there
are opportunities for prevention and intervention. However, few risk factors
distinguish between suicide ideators and decedents, pointing to an important
direction for future research.
PMID- 28502267
TI - Within-host interference competition can prevent invasion of rare parasites.
AB - Competition between parasite species or genotypes can play an important role in
the establishment of parasites in new host populations. Here, we investigate a
mechanism by which a rare parasite is unable to establish itself in a host
population if a common resident parasite is already present (a 'priority
effect'). We develop a simple epidemiological model and show that a rare parasite
genotype is unable to invade if coinfecting parasite genotypes inhibit each
other's transmission more than expected from simple resource partitioning. This
is because a rare parasite is more likely to be in multiply-infected hosts than
the common genotype, and hence more likely to pay the cost of reduced
transmission. Experiments competing interfering clones of bacteriophage infecting
a bacterium support the model prediction that the clones are unable to invade
each other from rare. We briefly discuss the implications of these results for
host-parasite ecology and (co)evolution.
PMID- 28502266
TI - Refining the Frommelt Attitude Toward the Care of the Dying Scale (FATCOD-B) for
medical students: A confirmatory factor analysis and Rasch validation study.
AB - OBJECTIVE: Given the increasing number of patients requiring palliative care and
the need for more professionals who are able to provide care for the dying
comfortably, assessment of medical attitudes toward end-of-life care is becoming
a key aspect of medical education. The present study aimed to establish whether
the Frommelt Attitude Toward the Care Of the Dying, Form B (FATCOD-B) meets
current psychometric standards of validity for an assessment tool in medical
education. METHOD: The participants were 200 undergraduate medical students.
Since in a previous study the FATCOD-B was found to have a weak structure due to
poor item validity, a refined version was proposed and tested in the present
study. Confirmatory factor analysis and the Rasch model were employed to assess
its dimensionality and psychometric properties. RESULTS: The construct measured
by the FATCOD-B continues to be misspecified. The tool has a two-dimensional
structure. The first is well-structured and demonstrates appreciable measurement
and discriminant capabilities. The second has low validity because its
measurement capabilities are based on weakly correlated items. SIGNIFICANCE OF
RESULTS: Our results suggest that the FATCOD-B measures a two-dimensional
construct and that only its first dimension is a robust measurement tool for use
in medical education to evaluate undergraduates' attitudes about caring for the
dying.
PMID- 28502268
TI - Comparison of two-dimensional and three-dimensional echocardiographic strain in
children with CHD.
AB - BACKGROUND: In CHD, three-dimensional strain analysis may overcome limitations of
Doppler and two-dimensional strain of the left ventricle. The aims of this study
were to evaluate feasibility and reproducibility of three-dimensional
longitudinal, circumferential, and radial systolic strain by three-dimensional
speckle-tracking echocardiography compared with two-dimensional echocardiography.
METHODS: Patients with CHD, biventricular circulation with a systemic left
ventricle, and who had two- and three-dimensional imaging performed on the same
day from 2010 to 2014 were included. Quantitative two- and three-dimensional
strain analyses were performed (two-dimensional cardiac performance analysis
version 1.2 and four-dimensional left ventricular analysis version 3.1). Intra-
and inter-observer variabilities were calculated on 25 studies. RESULTS: A total
of 30 patients, including 19 (61%) males, with a median age of 3.6 years (0.1-22
years) were included. The mean fractional shortening was 34.6+/-5.3%, and the
mean ejection fraction was 62.0+/-6.4%. Measurement of two- and three-dimensional
strain was feasible in >95% of segments. Good correlation was observed between
longitudinal and circumferential strain (r=0.92, p?0.001 and r=0.87, p?0.001),
but not radial strain (r=0.29, p=0.2). Intra- and inter-observer agreements were
better for three-dimensional compared with two-dimensional strain, and better for
both two- and three-dimensional longitudinal and circumferential strains compared
with radial strain. CONCLUSION: Left ventricular three-dimensional strain
analysis is feasible in children with CHD. The reproducibility of longitudinal
and circumferential strain by three-dimensional analyses is better. Further
longitudinal studies are warranted for the potential clinical application of this
new technology.
PMID- 28502269
TI - PENEPMA: A Monte Carlo Program for the Simulation of X-Ray Emission in Electron
Probe Microanalysis.
AB - The Monte Carlo program PENEPMA performs simulations of X-ray emission from
samples bombarded with both electron and photon beams. It is based on the general
purpose Monte Carlo simulation package PENELOPE, an elaborate system for the
simulation of coupled electron-photon transport in arbitrary materials, and on
the geometry subroutine package PENGEOM, which tracks particles through complex
material structures defined by quadric surfaces. After a brief description of the
interaction models implemented in the simulation subroutines and of the structure
and operation of PENEPMA, we provide an overview of the capabilities of the
program along with several examples of its application to the modeling of
electron probe microanalysis measurements.
PMID- 28502270
TI - Insecure attachment predicts depression and death anxiety in advanced cancer
patients.
AB - : ABSTRACTObjective:The prevalence of depression as well as adjustment and
anxiety disorders is high in advanced cancer patients, and research exploring
intraindividual factors leading to high psychological distress is
underrepresented. Cancer patients' feelings about security and trust in their
healthcare providers have a significant influence on how they deal with their
disease. The perception of social support is affected by patients' attachment
styles and influences their reactions to feelings of dependency and loss of
control. We therefore aimed to explore attachment and its association with
psychological distress in patients with advanced cancer. METHOD: We obtained data
from the baseline measurements of a randomized controlled trial in advanced
cancer patients. Patients were sampled from the university medical centers of
Hamburg and Leipzig, Germany. The main outcome measures included the Patient
Health Questionnaire, the Death and Dying Distress Scale, the Memorial Symptom
Assessment Scale, and the Experience in Close Relationships Scale for assessing
attachment insecurity. RESULTS: A total of 162 patients were included. We found
that 64% of patients were insecurely attached (fearful-avoidant 31%, dismissing
17%, and preoccupied 16%). A dismissing attachment style was associated with more
physical symptoms but did not predict psychological distress. A fearful-avoidant
attachment style significantly predicted higher death anxiety and depression,
whereas preoccupied attachment predicted higher death anxiety only. Overall,
insecure attachment contributed to the prediction of depression (10%) and death
anxiety (14%). SIGNIFICANCE OF RESULTS: The concept of attachment plays a
relevant role in advanced cancer patients' mental health. Healthcare providers
can benefit from knowledge of advanced cancer patients' attachment styles and how
they relate to specific mental distress. Developing a better understanding of
patients' reactions to feelings of dependency and distressing emotions can help
us to develop individually tailored advanced cancer care programs and
psychotherapeutic interventions.
PMID- 28502271
TI - QUALITY OF SAMPLE SIZE ESTIMATION IN TRIALS OF MEDICAL DEVICES: HIGH-RISK DEVICES
FOR NEUROLOGICAL CONDITIONS AS EXAMPLE.
AB - BACKGROUND: The aim of this study was to assess the quality of reporting sample
size calculation and underlying design assumptions in pivotal trials of high-risk
medical devices (MDs) for neurological conditions. METHODS: Systematic review of
research protocols for publicly registered randomized controlled trials (RCTs).
In the absence of a published protocol, principal investigators were contacted
for additional data. To be included, trials had to investigate a high-risk MD,
registered between 2005 and 2015, with indications stroke, headache disorders,
and epilepsy as case samples within central nervous system diseases. Extraction
of key methodological parameters for sample size calculation was performed
independently and peer-reviewed. RESULTS: In a final sample of seventy-one
eligible trials, we collected data from thirty-one trials. Eighteen protocols
were obtained from the public domain or principal investigators. Data
availability decreased during the extraction process, with almost all data
available for stroke-related trials. Of the thirty-one trials with sample size
information available, twenty-six reported a predefined calculation and
underlying assumptions. Justification was given in twenty and evidence for
parameter estimation in sixteen trials. Estimates were most often based on
previous research, including RCTs and observational data. Observational data were
predominantly represented by retrospective designs. Other references for
parameter estimation indicated a lower level of evidence. CONCLUSIONS: Our
systematic review of trials on high-risk MDs confirms previous research, which
has documented deficiencies regarding data availability and a lack of reporting
on sample size calculation. More effort is needed to ensure both relevant
sources, that is, original research protocols, to be publicly available and
reporting requirements to be standardized.
PMID- 28502272
TI - Adverse childhood experiences, exposure to a natural disaster and posttraumatic
stress disorder among survivors of the 2011 Great East Japan earthquake and
tsunami.
AB - AIMS: To investigate whether adverse childhood experiences (ACEs) modify the
impact of exposure to a natural disaster (the 2011 Great East Japan earthquake
and tsunami) on the occurrence of posttraumatic stress disorder (PTSD) among
older people. METHODS: Data were collected as part of the Japan Gerontological
Evaluation Study (JAGES), which is an on-going epidemiological survey
investigating social determinants of health among older people across Japan.
Information on PTSD symptoms based on the Screening Questionnaire for Disaster
Mental Health, traumatic exposure to the earthquake (i.e., house damage and loss
of relatives/friends during the earthquake/tsunami) and ACEs was obtained from
580 participants aged 65 or older living in Iwanuma City, Miyagi Prefecture,
which suffered severe damage as a result of the earthquake and the subsequent
tsunami in March 2011. Associations were examined using Poisson regression
analysis with a robust variance estimator after adjusting for covariates.
RESULTS: The prevalence of PTSD was 9.7% in this population; compared to those
with no traumatic experience, the prevalence of PTSD was approximately two times
higher among those who experienced the loss of close friends/relatives (PR =
1.84, 95% CI = 1.11-3.03, p = 0.018), or whose house was damaged (PR = 2.15, 95%
CI = 1.07-4.34, p = 0.032). ACE was not significantly associated with PTSD.
Stratified analyses by the presence of ACE showed that damage due to the
earthquake/tsunami was associated with PTSD only among those without ACEs; more
specifically, among non-ACE respondents the PR of PTSD associated with house
damage was 6.67 (95% CI = 1.66-26.80), while for the loss of a relative or a
close friend it was 3.56 (95% CI = 1.18-10.75). In contrast, no statistically
significant associations were observed among those with ACEs. CONCLUSION:
Following the Great East Japan earthquake/tsunami in 2011 a higher risk of
developing PTSD symptoms was observed in 2013 especially among older individuals
without ACEs. This suggests that ACEs might affect how individuals respond to
subsequent traumatic events later in life.
PMID- 28502273
TI - Modiolar ossification in paediatric patients with auditory neuropathy.
AB - OBJECTIVE: To describe our finding of increased ossification of the modiolus in
paediatric patients with auditory neuropathy who met criteria for cochlear
implantation. METHODS: A retrospective case series with a comparison group at a
tertiary referral centre is described. Seven paediatric patients with auditory
neuropathy who met criteria for and underwent cochlear implantation were
identified. Fifteen paediatric implantees with bilateral profound sensorineural
hearing loss were included as the comparison group. All patients underwent pre
operative computed tomography. Attenuation at the modiolus was measured in all
subjects by a neuroradiologist blinded to clinical information. RESULTS:
Attenuation values in the modiolus in the auditory neuropathy patients (mean +/-
standard deviation = 796.2 +/- 53.0 HU) was statistically significantly higher
than in the comparison sensorineural hearing loss patients (267.1 +/- 45.6 HU; p
< 0.05, t-test). CONCLUSION: Patients with auditory neuropathy who meet criteria
for cochlear implantation demonstrate significantly higher modiolar attenuation
on computed tomography imaging, consistent with increased ossification at the
modiolus.
PMID- 28502274
TI - Superior petrosal sinus causing superior canal dehiscence syndrome.
AB - OBJECTIVE: To determine signs and symptoms for superior canal dehiscence syndrome
caused by the superior petrosal sinus. METHODS: A review of the English-language
literature on PubMed and Embase databases was conducted, in addition to a multi
centre case series report. RESULTS: The most common symptoms of 17 patients with
superior petrosal sinus related superior canal dehiscence syndrome were: hearing
loss (53 per cent), aural fullness (47 per cent), pulsatile tinnitus (41 per
cent) and pressure-induced vertigo (41 per cent). The diagnosis was made by
demonstration of the characteristic bony groove of the superior petrosal sinus
and the 'cookie bite' out of the superior semicircular canal on computed
tomography imaging. CONCLUSION: Pulsatile tinnitus, hearing loss, aural fullness
and pressure-induced vertigo are the most common symptoms in superior petrosal
sinus related superior canal dehiscence syndrome. Compared to superior canal
dehiscence syndrome caused by the more common apical location of the dehiscence,
pulsatile tinnitus and exercise-induced vertigo are more frequent, while sound
induced vertigo and autophony are less frequent. There is, however, considerable
overlap between the two subtypes. The distinction cannot as yet be made on
clinical signs and symptoms alone, and requires careful analysis of computed
tomography imaging.
PMID- 28502275
TI - Use of acellular dermal matrices in laryngotracheal and pharyngeal
reconstruction: systematic review.
AB - BACKGROUND: Acellular dermal matrices are increasingly used in laryngotracheal
and pharyngeal reconstruction, but specific indications and the type of acellular
dermal matrix used vary. The authors systematically reviewed outcomes relating to
acellular dermal matrix use in head and neck reconstruction. METHODS: Electronic
databases were searched through 1 May 2016 for literature on acellular dermal
matrix use in laryngotracheal and pharyngeal reconstruction. Studies were
appraised for surgical indications, outcomes and study design. RESULTS: Eleven
publications with 170 cases were included. Eight articles reported on acellular
dermal matrix use in oncological reconstruction. Most studies were case series;
no high-level evidence studies were identified. Graft extrusion was more common
in non-oncological applications. In general, post-oncological reconstruction with
an acellular dermal matrix demonstrated complication rates similar to those
reported without an acellular dermal matrix. CONCLUSION: Evidence in support of
acellular dermal matrix use in head and neck reconstruction is generally poor.
Prospective comparative studies are required to define the indications, safety
and effectiveness of acellular dermal matrices in laryngotracheal and pharyngeal
reconstruction.
PMID- 28502276
TI - Characterization of tabanid flies (Diptera: Tabanidae) in South Africa and Zambia
and detection of protozoan parasites they are harbouring.
AB - Tabanids are haematophagous flies feeding on livestock and wildlife. In the
absence of information on the relationship of tabanid flies and protozoan
parasites in South Africa and Zambia, the current study was aimed at
characterizing tabanid flies collected in these two countries as well as
detecting protozoan parasites they are harbouring. A total of 527 tabanid flies
were collected whereby 70.2% were from South Africa and 29.8% were from Zambia.
Morphological analysis revealed a total of five different genera collected from
the sampled areas namely: Ancala, Atylotus, Haematopota, Philoliche and Tabanus.
DNA extracted from South African Tabanus par and Tabanus taeniola tested positive
for the presence of Trypanosoma congolense (Savannah) and Trypanosoma theileri
whilst one member from T. par was positive for Trypanosoma brucei species. DNA
extracted from Zambian tabanid flies tested positive for the presence of
Besnoitia species at 1.27% (2/157), Babesia bigemina 5.73% (9/157), Theileria
parva 30.11% (30/157) and 9.82% (14/157) for Trypanosoma evansi. This study is
the first to report on relationship of Babesia and Theileria parasites with
tabanid flies. Further investigations are required to determine the role of
tabanids in transmission of the detected protozoan parasites in livestock and
wildlife in South Africa and Zambia.
PMID- 28502277
TI - Lactobacillus paracasei GMNL-32, Lactobacillus reuteri GMNL-89 and L. reuteri
GMNL-263 ameliorate hepatic injuries in lupus-prone mice.
AB - Probiotics are known to regulate host immunity by interacting with systemic and
mucosal immune cells as well as intestinal epithelial cells. Supplementation with
certain probiotics has been reported to be effective against various disorders,
including immune-related diseases. However, little is known about the
effectiveness of Lactobacillus paracasei GMNL-32 (GMNL-32), Lactobacillus reuteri
GMNL-89 (GMNL-89) and L. reuteri GMNL-263 (GMNL-263) in the management of
autoimmune diseases, especially systemic lupus erythematosus (SLE). NZB/W F1
mice, which are a lupus-prone animal model, were orally gavaged with GMNL-32,
GMNL-89 or GMNL-263 to investigate the effects of these Lactobacillus strains on
liver injuries in NZB/W F1 mice. The results thus obtained reveal that
supplementary GMNL-32, GMNL-89 or GMNL-263 in NZB/W F1 mice ameliorates hepatic
apoptosis and inflammatory indicators, such as matrix metalloproteinase-9
activity and C-reactive protein and inducible nitric oxide synthase expressions.
In addition, supplementation with GMNL-32, GMNL-89 or GMNL-263 in NZB/W F1 mice
reduced the expressions of hepatic IL-1beta, IL-6 and TNF-alpha proteins by
suppressing the mitogen-activated protein kinase and NF-kappaB signalling
pathways. These findings, presented here for the first time, reveal that GMNL-32,
GMNL-89 and GMNL-263 mitigate hepatic inflammation and apoptosis in lupus-prone
mice and may support an alternative remedy for liver disorders in cases of SLE.
PMID- 28502278
TI - A NEW HEALTH TECHNOLOGY ASSESSMENT SYSTEM FOR DEVICES: THE FIRST FIVE YEARS.
AB - OBJECTIVES: The aim of this study was to review 5 years of activity from a new
system devised by the National Institute for Health and Care Excellence (NICE),
for assessing medical devices and diagnostics aimed at identifying and speeding
adoption of technologies with clinical and cost advantages, compared with current
practice in the United Kingdom healthcare system. METHODS: All eligible notified
technologies were classified using the Food and Drug Administration and Global
Medical Device Nomenclature nomenclatures. Decisions about selecting technologies
for full assessment to produce NICE recommendations were reviewed, along with the
reasons given to companies for not selecting products. RESULTS: Between 2009 and
2014, 186 technologies were notified (46 percent therapeutic and 54 percent
diagnostic). Thirty-nine were judged ineligible (no regulatory approval), and 147
were considered by an independent committee. Of these, eighty (54 percent) were
not selected for full assessment, most commonly because of insufficient evidence
(86 percent): there were uncertainties specifically about benefits to the health
service (54 percent), to patients (39 percent), and about cost (24 percent). The
remaining 67 were selected and assessed for Medical Technology guidance (52
percent) (noninferior and/or lower cost consequences than current practice), for
Diagnostics guidance (43 percent) or other NICE recommendations about adoption
and use. Classifying technologies by two different systems showed no selection
bias for any technology type or disease area. CONCLUSIONS: Identifying new or
under-used devices and diagnostics with potential benefits and promoting their
adoption is important to health services in the United Kingdom and worldwide.
This new system offers a means of fostering both uptake and further research.
Lack of research data on new products is a major obstacle to evaluation.
PMID- 28502279
TI - Evidence and molecular characterization of Bartonella spp. and hemoplasmas in
neotropical bats in Brazil.
AB - The order Chiroptera is considered the second largest group of mammals in the
world, hosting important zoonotic virus and bacteria. Bartonella and hemotropic
mycoplasmas are bacteria that parasite different mammals' species, including
humans, causing different clinical manifestations. The present work aimed
investigating the occurrence and assessing the phylogenetic positioning of
Bartonella spp. and Mycoplasma spp. in neotropical bats sampled from Brazil.
Between December 2015 and April 2016, 325 blood and/or tissues samples were
collected from 162 bats comprising 19 different species sampled in five states of
Brazil. Out of 322 bat samples collected, while 17 (5.28%) were positive to
quantitative PCR for Bartonella spp. based on nuoG gene, 45 samples (13.97%) were
positive to cPCR assays for hemoplasmas based on 16S rRNA gene. While seven
sequences were obtained for Bartonella (nuoG) (n = 3), gltA (n = 2), rpoB (n =
1), ftsZ (n = 1), five 16S rRNA sequences were obtained for hemoplasmas. In the
phylogenetic analysis, the Bartonella sequences clustered with Bartonella
genotypes detected in bats sampled in Latin America countries. All five
hemoplasmas sequences clustered together as a monophyletic group by Maximum
Likelihood and Bayesian Inference analyses. The present work showed the first
evidence of circulation of Bartonella spp. and hemoplasmas among bats in Brazil.
PMID- 28502280
TI - A Feedback-Controlled Mandibular Positioner Identifies Individuals With Sleep
Apnea Who Will Respond to Oral Appliance Therapy.
AB - STUDY OBJECTIVES: Mandibular protruding oral appliances represent a potentially
important therapy for obstructive sleep apnea (OSA). However, their clinical
utility is limited by a less-than-ideal efficacy rate and uncertainty regarding
an efficacious mandibular position, pointing to the need for a tool to assist in
delivery of the therapy. The current study assesses the ability to prospectively
identify therapeutic responders and determine an efficacious mandibular position.
METHODS: Individuals (n = 202) with OSA participated in a blinded, 2-part
investigation. A system for identifying therapeutic responders was developed in
part 1 (n = 149); the predictive accuracy of this system was prospectively
evaluated on a new population in part 2 (n = 53). Each participant underwent a 2
night, in-home feedback-controlled mandibular positioner (FCMP) test, followed by
treatment with a custom oral appliance and an outcome study with the oral
appliance in place. A machine learning classification system was trained to
predict therapeutic outcome on data obtained from FCMP studies on part 1
participants. The accuracy of this trained system was then evaluated on part 2
participants by examining the agreement between prospectively predicted outcome
and observed outcome. A predicted efficacious mandibular position was derived
from each FCMP study. RESULTS: Predictive accuracy was as follows: sensitivity
85%; specificity 93%; positive predictive value 97%; and negative predictive
value 72%. Of participants correctly predicted to respond to therapy, the
predicted mandibular protrusive position proved efficacious in 86% of cases.
CONCLUSIONS: An unattended, in-home FCMP test prospectively identifies
individuals with OSA who will respond to oral appliance therapy and provides an
efficacious mandibular position. CLINICAL TRIAL REGISTRATION: The trial that this
study reports on is registered on www.clinicaltrials.gov, ID NCT03011762, study
name: Feasibility and Predictive Accuracy of an In-Home Computer Controlled
Mandibular Positioner in Identifying Favourable Candidates for Oral Appliance
Therapy.
PMID- 28502281
TI - Self-Reported Sleep Duration and Self-Rated Health in Young Adults.
AB - STUDY OBJECTIVES: This study aimed to determine the associations between the self
reported sleep duration and self-rated health in young adults. METHODS: In this
cross-sectional study, participants were 689 young adults (mean age 20 +/- 1.35
years, 49.8% female). Sleep duration and self-rated health, as the main outcome
of interest, were measured as self-reported. As potential covariates, we included
sex, age, smoking status, alcohol consumption, physical activity, sedentary
behavior, psychological distress, and body mass index. RESULTS: Approximately 30%
of participants slept 7-8 hours, 17.4% were short sleepers (categories < 6 hours
and 6-7 hours), and 53.9% were long sleepers (categories 8-10 hours and > 10
hours of sleep). In an unadjusted model, compared with the reference category (7
8 hours of sleep), those who slept < 6 hours (odds ratio 0.20; 95% confidence
interval 0.08 to 0.48) and between 6-7 hours (odds ratio 0.43; 95% confidence
interval 0.26 to 0.69) were less likely to have good self-rated health. In an
adjusted model, short (< 7 hours) and long sleep (> 10 hours) were both
associated with poor self-rated health. CONCLUSIONS: Our results suggest that
both short (< 7 hours) and long (> 10 hours) sleepers have lower odds of having
good self-rated health after adjusting for potential covariates. Health
professionals should pay more attention to young adults, who have both short and
long period of sleep, in order to prevent health problems and potential acute or
chronic diseases.
PMID- 28502283
TI - Why Should We Care About Selenium in Obstructive Sleep Apnea?
PMID- 28502282
TI - Morning Diastolic Blood Pressure May Be Independently Associated With Severity of
Obstructive Sleep Apnea in Non-Hypertensive Patients: A Cross-Sectional Study.
AB - STUDY OBJECTIVES: The aim of the study is to verify a possible association
between arterial blood pressure and obstructive sleep apnea (OSA) severity in a
group of non-hypertensive patients. METHODS: This is a retrospective study of
1,171 consecutive patients referred to the sleep laboratory with complaints
suggestive of OSA who underwent standard diagnostic polysomnography. In total,
454 patients with no History of arterial hypertension nor had received any such
treatment were selected from this group. RESULTS: Patients with severe OSA (apnea
hypopnea index [AHI] >= 30 events/h) presented with higher diastolic blood
pressure (DBP) in the morning than healthy subjects (AHI < 5 events/h) or those
suffering from mild (15 < AHI >= 5 events/h) or moderate OSA (30 < AHI >= 15
events/h): 86.2 +/- 11.3 versus 79.2 +/- 8.5, 80.3 +/- 10.2 and 81.4 +/- 9.6
mmHg, P < .01, respectively. In a linear regression model, a rise in morning DBP
was predicted by AHI (beta = 0.14, P < .001) and body mass index (BMI) (beta =
0.22, P < .01), but not by age (beta = 0.01, P = .92), male sex (beta = -0.06, P
= .19), or smoking (beta = 0.01, P = .86). In contrast, no association existed
between morning systolic blood pressure (SBP) and AHI independently of BMI, sex,
age, or smoking. High blood pressure (ie, SBP >= 140 mmHg or DBP >= 90 mmHg on
each of three measurements on different occasions) was predicted by age of 42
years or older, BMI of at least 29 kg/m2, and severe OSA. CONCLUSIONS: High AHI,
independent of obesity, age and sex, was associated with elevated DBP in the
morning. Thus, elevated morning DBP may be one of the symptoms related to OSA
that warrants specific diagnostics. COMMENTARY: A commentary on this article
appears in this issue on page 861.
PMID- 28502284
TI - Should Hyperarousal and Sleep Fragmentation Be Additional Treatment Targets When
Treating OSA in PTSD With CPAP?
PMID- 28502285
TI - The Continued Search for Optimal Therapy in Patients With OSA and PTSD.
PMID- 28502286
TI - Do Obese Children Require Inpatient Monitoring After Adenotonsillectomy?
PMID- 28502287
TI - The Need for a Reliable Sleep EEG Biomarker.
PMID- 28502288
TI - Portable Sleep Monitoring Systems: Broadening the Horizons.
PMID- 28502289
TI - Chronophin activation is necessary in Doxorubicin-induced actin cytoskeleton
alteration.
AB - Although doxorubicin (Dox)-induced oxidative stress is known to be associated
with cytotoxicity, the precise mechanism remains unclear. Genotoxic stress not
only generates free radicals, but also affects actin cytoskeleton stability. We
showed that Dox-induced RhoA signaling stimulated actin cytoskeleton alterations,
resulting in central stress fiber disruption at early time points and cell
periphery cortical actin formation at a later stage, in HeLa cells.
Interestingly, activation of a cofilin phosphatase, chronophin (CIN), was
initially evoked by Dox-induced RhoA signaling, resulting in a rapid
phosphorylated cofilin turnover leading to actin cytoskeleton remodeling. In
addition, a novel interaction between CIN and 14-3-3zeta was detected in the
absence of Dox treatment. We demonstrated that CIN activity is quite contrary to
14-3-3zeta binding, and the interaction leads to enhanced phosphorylated cofilin
levels. Therefore, initial CIN activation regulation could be critical in Dox
induced actin cytoskeleton remodeling through RhoA/cofilin signaling. [BMB
Reports 2017; 50(6): 335-340].
PMID- 28502291
TI - [ABIN1 is not involved in imatinib upregulating A20 to inhibit the activation of
NF-kappaB pathway in Jurkat T cells].
AB - Objective To investigate the effect of imatinib (IM) on the expressions of A20
binding inhibitor of NF-kappaB1 (ABIN1) and A20 in Jurkat T cells. Methods Jurkat
T cells were treated with 25, 50 and 100 nmol/L IM for 24 hours. The mRNA and
protein levels of ABIN1, A20 and NF-kappaB were detected by real-time
quantitative PCR and Western blotting. Results IM significantly inhibited both
mRNA and protein levels of ABIN1 and NF-kappaB, but raised the mRNA and protein
levels of A20; while phorbol 12-myristate 13-acetate/ionomycin increased the
expression levels of ABIN1 and A20 mRNA and protein. Conclusion IM could
upregulate A20 protein to inhibit the activation of NF-kappaB pathway in Jurkat T
cells, which was independent of the ABIN1 protein.
PMID- 28502290
TI - Deubiquitinase YOD1: the potent activator of YAP in hepatomegaly and liver
cancer.
AB - Advances in the understanding of the Hippo signaling as a key regulatory pathway
of proliferation and apoptosis have provided mechanical insights for controlling
organ size and tumorigenicity. Recently, much attention has been directed to the
regulation of LATS1/2 (large tumor suppressor) kinases that phosphorylate
YAP/TAZ, a transcriptional co-activator in the Hippo pathway, and control the
level and nuclear localization of YAP/TAZ. In our recent work, we showed that
deubiquitinase YOD1 stabilizes ITCH, and facilitates ITCH-mediated LATS1/2
ubiquitination and degradation, resulting in increased YAP/TAZ level.
Furthermore, we found that the YOD1- ITCH-LATS1/2-YAP/TAZ signaling axis is
controlled by the differential expression of miR-21 in a cell-density-dependent
manner. Using a transgenic mouse model, we showed that the inducible expression
of YOD1 enhances the proliferation of hepatocytes and leads to hepatomegaly in a
YAP/TAZ-activitydependent manner. Moreover, a strong correlation was observed
between YOD1 and YAP expression in liver cancer patients. Overall, our data
suggest that YOD1 is a novel regulator of the Hippo pathway, and thereby a
potential therapeutic target for liver cancer. [BMB Reports 2017; 50(6): 281
282].
PMID- 28502292
TI - [Autophagy modulates the levels of inflammatory cytokines in macrophages induced
by lipopolysaccharide].
AB - Objective To analyze the effect of autophagy on inflammatory response in
macrophages induced by lipopolysaccharide (LPS) and investigate its molecular
mechanism. Methods Bone marrow mesenchymal stem cells, which were separated from
the femora of mice, were cultured and induced to differentiate into primary
macrophages in vitro. The inflammatory cell model was established by stimulating
the primary macrophages with LPS. Autophagy was inhibited by 3-methyladenine (3
MA) or promoted by rapamycin. Green fluorescent protein-microtubule associated
protein 1 light chain 3 (GFP-LC3) plasmid was used to transfect primary
macrophages and the percentage of cells with GFP-LC3 puncta were counted in the
different groups. The mRNA levels of LC3B, tumor necrosis factor alpha (TNF
alpha), interleukin 1beta (IL-1beta), IL-6 and IL-12p40 were detected by real
time quantitative PCR, and the protein levels of LC3B, nuclear factor kappaB (NF
kappaB) and IkappaBalpha were determined by Western blotting. Results LC3B mRNA
and protein expression levels were gradually up-regulated and the autophagosomes
increased in the macrophages 2, 4 and 6 hours after treated by LPS. Compared with
only LPS treatment group, autophagy inhibition by 3-MA pretreatment promoted the
mRNA expressions of inflammatory cytokines including TNF-alpha, IL-1beta, IL-6
and IL-12p40, and the autophagy induction by rapamycin pretreatment suppressed
TNF-alpha, IL-1beta, IL-6 and IL-12p40. Meanwhile, 3-MA or rapamycin pretreatment
further regulated the protein expressions of IkappaBalpha and p-NF-kBp65 induced
by LPS in macrophages. Conclusion Autophagy can suppress the LPS-induced
inflammatory response in macrophages by regulating NF-kappaB signaling pathway.
PMID- 28502293
TI - [Wuwei Wentong Chubi Capsule promotes the autophagy in synovial tissue of
adjuvant-induced arthritis rats and its mechanism].
AB - Objective To evaluate the effect of Wuwei Wentong Chubi (WWWTCB) Capsule on the
PI3K/AKT/mTOR signaling pathway in the synovial tissues of adjuvant-induced
arthritis (AA) rats, and investigate its potential pharmacological mechanisms of
treating rheumatoid arthritis. Methods Sixty Sprague Dawley (SD) rats were
randomly assigned into six groups evenly: normal group, model group, WWWTCB
groups at 0.80, 1.60, 3.20 g/kg body mass, and tripterygium glycosides tablet
(TPT) group at 40 mg/kg body mass. Except for the normal group, the other five
groups were induced into AA models with Complete Freund's Adjuvant (CFA). The
WWWTCB or TPT, was administrated from day 12 after injection of CFA by gavage,
once a day for 12 days. After that, unaffected ankle-joint tissues from the AA
rats were collected for histopathological examination. The mRNA levels of PI3K,
AKT, mTOR, p70s6 and beclin1 in the synovial tissue were detected by real-time
quantitative PCR. Meanwhile, the protein levels of PI3K, AKT, p-AKT, mTOR, p
mTOR, p70s6, p-p70s6 and beclin1 were determined by immunofluorescence
histochemical staining and/or Western blotting. Results Compared with the model
group, WWWTCB (1.60, 3.20 g/kg body mass) groups showed less ankle-joint injury
and decreased proliferation of synovial cells in the ankle-joint tissues. In
addition, the administration of WWWTCB decreased the mRNA and protein levels of
PI3K, AKT, p-AKT, mTOR, p-mTOR, p70s6 and p-p70s6, while increased the level of
beclin1. Conclusion WWWTCB ameliorated AA in rats. The improvement might be
closely related to the inhibitory effect of WWWTCB on the PI3K/AKT/mTOR signaling
pathway and its promoting effect on the autophagy activity of synovial cells.
PMID- 28502294
TI - [Resiquimod (R848) has more stronger immune adjuvantivity than other tested TLR
agonists].
AB - Objective To compare and characterize the Th1 immune responses induced by the
most commonly used commercial Toll-like receptor (TLR) agonists through in vivo
and ex vivo experiments. Methods The concentrations of IL-12 were tested by ELISA
after mouse dendritic cells (DCs) in vitro were stimulated by one of tested TLR
agonists, including poly(I:C), monophosphoryl lipid A (MPLA), resiquimod (R848),
cytosine polyguanine-C (CpG-C). The changes in percentage and phenotype of DCs,
NK cells and effector T cells in the draining lymph nodes were analyzed by flow
cytometry after BALB/c mice were immunized with ovalbumin (OVA) mixed with
selected TLR agonist. The serum concentrations of specific anti-OVA IgG2a in the
immunized mice were determined by ELISA. Results Only CpG-C and R848 could
significantly induce the production of IL-12 from bone marrow-derived DCs in
vitro. Among the tested TLR agonists, R848 was the most effective adjuvant in
recruiting DCs and NK cells into lymph nodes, inducing the proliferation of CD4+
and CD8+ effector T cells and the production of specific anti-OVA IgG2a in vivo.
Conclusion R848 was the most potential Th1-promoting adjuvant among the tested
TLR agonists.
PMID- 28502295
TI - [Lactobacillus rhamnosus GG improves symptoms and its mechnism in mice with
ovalbumin-induced food allergy].
AB - Objective To investigate the effect of Lactobacillus rhamnosus GG (LGG) on
peripheral blood IL-4/IFN-gamma in mice with ovalbumin-induced food allergy.
Methods The mice with food allergy were divided into 3 groups (n=10 in each
group): food allergy model group, low-dose LGG group (1*108 CFU/mL, 200 MUL/d)
and high-dose LGG group (1*109 CFU/mL, 200 MUL/d). The healthy mice (n=10) served
as a control group. Mice in the LGG groups were given LGG for consecutive 22 days
after modeling. The control mice and the food allergy model mice were given
normal saline instead of LGG. At day 23, the allergic score, body mass, thymus
index, spleen index were recorded and calculated; the expressions of IgE, IL-4
and IFN-gamma in peripheral blood were detected by ELISA; the pathological
changes of small intestines were observed by HE staining and fecal flora were
examined by bacterial culture. Results The thymus and spleen indexes had no
significant differences within the 4 groups. Compared with the control group, IL
4, allergic score, E.coli and bacteroides increased, and IFN-gamma, IFN-gamma/IL
4, IgE, body mass, Bifidobacterium and Lactobacillus decreased in the mice with
food allergy. Compared with the mice with food allergy, IL-4, allergic score,
E.coli and Bacteroides decreased significantly, and IFN-gamma, IFN-gamma/IL-4,
IgE, body mass, Bifidobacterium and Lactobacillus significantly increased in the
LGG groups in a dose-dependent manner. In the food allergy model group, some
edematous and necrotic epithelial cells were found in intestinal mucosa. Compared
with the food allergy model group, the intestinal mucosa was integrated and the
intestinal cells appeared ordered in the LGG groups. Conclusion LGG can
remarkably improve the symptoms of ovalbumin-induced food allergy probably by
decreasing IL-4/IFN-gamma ratio.
PMID- 28502296
TI - [Recombinant Legionella pneumophila flagella protein A (rflaA) induces the
secretion of IL-6 and IL-1beta in RAW264.7 cells in vitro].
AB - Objective To investigate the effect of recombinant Legionella pneumophila
flagella protein A (rflaA) on the secretion of interleukin-6 (IL-6) and
interleukin-1beta (IL-1beta) by RAW264.7 macrophage and the possible mechanism.
Methods RAW264.7 cells were treated with 0.000, 0.125, 0.250, 0.500, 1.000,
2.000, 4.000 and 8.000 MUg/mL rflaA to determine the EC50 of rflaA using CCK-8
assay. Secretion of IL-6 and IL-1beta were measured by ELISA at 24, 36 and 48
hours after treatment of the cells with 0.04, 0.08 and 0.16 MUg/mL rflaA. At 6,
12, 24, 36 and 48 hours after treatment of the cells with 0.04, 0.08 and 0.16
MUg/mL rflaA, the expressions of IL-6, IL-1beta, NOD-like receptor protein 3
(NLRP3) and caspase-1 mRNAs were detected by quantitative real-time PCR, and the
expressions of NLRP3 and caspase-1 proteins were tested by Western blotting.
Results RflaA enhanced the expressions of IL-6 and IL-1beta, and the higher
concentration of rflaA was more potential. The expressions of IL-6 and IL-1beta
reached peak when the cells were treated with 0.16 MUg/mL rflaA for 36 hours.
Treatment of RAW264.7 cells with rflaA promoted the expressions of IL-6 and IL
1beta, NLRP3 and caspase-1 mRNA, and 0.16 MUg/mL rflaA was the most potential at
12 hours after treatment. Expressions of NLRP3 and caspase-1 protein increased
after treatment with rflaA, and 0.16 MUg/mL rflaA induced the highest expression
of both proteins at 24 hours after treatment. Conclusion RflaA could enhance the
secretion of IL-6 and IL-1beta by promoting the expressions of NLRP3 and caspase
1 in RAW264.7 cells.
PMID- 28502297
TI - [Knock-down of cadherin 17 inhibits proliferation and promote apoptosis in
noscapine-resistant human SW480 colon cancer cells].
AB - Objective To investigate the effects of cadherin 17 (CDH17) on the proliferation
and apoptosis of noscapine-resistant human SW480 colon cancer cells. Methods The
level of CDH17 in noscapine-resistant human SW480 colon cancer cells was knocked
down by small interfering RNA (siRNA), and the silence was confirmed by Western
blotting and real-time quantitative PCR. Transfected SW480 cells were treated
with noscapine, and then the proliferation and cell viability of SW480 cells were
measured by MTT assay and plate clone formation assay, respectively; the
apoptosis of SW480 cells was detected by flow cytometry combined with annexinV
FITC/PI staining; the expressions of poly-ADP-ribose polymerase (PARP) and
caspase-3 were determined by Western blotting. Results Compared with NC-siRNA
group and control group, the expression levels of CDH17 protein and mRNA were
down-regulated in the CDH17-siRNA-transfected SW480 cell lines. After noscapine
treatment, compared with NC-siRNA and control group, the colony-forming ratio and
cell viability were significantly lower in CDH17-siRNA -transfected cell lines,
and the expression levels of cleaved-PARP and cleaved- caspase-3 were up
regulated in CDH17-siRNA group, and the cell apoptosis rate increased. Conclusion
Knock-down of CDH17 in SW480 cells can effectively inhibit cell proliferation and
promote cell apoptosis as well as improve SW480 cell sensitivity to narcotine.
PMID- 28502298
TI - [Forkhead domain inhibitor-6 (FDI-6) increases apoptosis and inhibits invasion
and migration of laryngeal carcinoma cells by down-regulating nuclear FoxM1].
AB - Objective To study the effects of new small molecular inhibitor, forkhead domain
inhibitor-6 (FDI-6), on proliferation, apoptosis, invasion and migration in human
laryngeal carcinoma Hep-2 cell line and the related mechanism. Methods MTT assay
was used to test the proliferation rate of Hep-2 cells before and 12, 24 hours
after treated with (5, 10, 20, 40, 80) MUmol/L of FDI-6. Flow cytometry (FCM) and
TranswellTM chamber assay were respectively carried out to detect the apoptosis
rate, cell invasion and migration in Hep-2 cells after treated by 10, 20 MUmol/L
FDI-6 for 24 hours. Real-time quantitative PCR (qRT-PCR) and Western blotting
were performed to determine the mRNA and protein levels of FoxM1, Bcl-2 and BAX,
respectively. Results Cell proliferation rate was inhibited by FDI-6 in a dose-
and time-dependent manner. Twenty-four hours after 10, 20 MUmol/L FDI-6
treatment, the apoptosis rate in Hep-2 cells was elevated and the ability of cell
invasion and migration was inhibited in a dose-dependent manner. The qRT-PCR
showed that there was no significant change in FoxM1 mRNA expression with or
without FDI-6 treatment. Western blotting showed that the total protein level of
FoxM1 was not obviously changed, but Bcl-2 was down-regulated, BAX was up
regulated. However, in the nuclear FoxM1 protein level decreased along with the
ascent of FDI-6 concentration. Conclusion FDI-6 could induce cell apoptosis and
inhibit cell proliferation, invasion and migration in Hep-2 cells. This may be
related to the down-regulation of FoxM1 in the nucleus.
PMID- 28502299
TI - [Tumor-associated macrophages promote the proliferation and migration as well as
invasion of sorafenib-resistant hepatocellular carcinoma cells].
AB - Objective To investigate the roles of tumor-associated macrophages (TAMs) and
epithelial growth factor receptor (EGFR)/beta-catenin signaling pathway in
sorafenib resistance of hepatocellular carcinoma cells. Methods Macrophages were
isolated from peripheral blood mononuclear cells (PBMCs) and cultured in the
presence of colony-stimulating factor (M-CSF) to obtain TAMs. Phenotypes of TAMs
were identified. The level of epithelial growth factor (EGF) secreted by TAMs was
detected by ELISA. CCK-8 assay was performed to verify the effects of EGF on
HepG2 and SMMC7721 cell proliferation. TranswellTM assay was used to examine the
effects of EGF on the invasion and migration ability of HepG2 and SMMC7721 cells.
TAMs and hepatocellular carcinoma cells were co-cultured to study the downstream
signaling pathways. Sorafenib-resistant HepG2 and SMMC7721 strains (R-HepG2 and R
SMMC7721 cells) were prepared and then subjected to Western blotting and
immunohistochemistry to examine the expression levels of beta-catenin and EGFR.
Results TAMs we prepared were confirmed. Compared with HepG2 and SMMC7721 cells,
R-HepG2 and R-SMMC7721 showed enhanced proliferation, invasion and migration
abilities. The growth rates of sorafenib-resistant cell lines after co-cultured
with TAMs were significantly higher than those of the controls. The protein
expressions of beta-catenin and EGFR in sorafenib-resistant cells and
hepatocellular carcinoma tissues were higher than those in the controls.
Conclusion TAMs and EGFR/beta-catenin signaling pathway promote the
proliferation, invasion and migration of sorafenib resistance of hepatocellular
carcinoma cells.
PMID- 28502300
TI - [Down-regulation of sphingosine kinase 1 (SphK1) enhances the chemosensitivity to
cisplatin in human colon cancer RKO cells].
AB - Objective To investigate the effect of sphingosine kinase 1 (SphK1) gene silence
on the sensitivity to cisplatin (DDP) in RKO colon cancer cell line and the
potential mechanism. Methods Targeted SphK1 gene lentivirus virus was constructed
to infect RKO cells. The relative mRNA expression of SphK1 was detected by
quantitative real-time PCR (qRT-PCR) and the protein level of SphK1 was
determined by Western blotting. Then RKO cells were divided into three groups:
down-regulated SphK1 group (shSphK1 group), negative control group (shControl
group) and blank control group (control group). Cells of these groups were
incubated for 0, 24, 48 and 72 hours with 0, 2, 4, 8, 16, 32 MUg/mL DDP. After
treatment, cell viability was evaluated by MTT assay. Cell apoptosis index was
determined by TUNEL. The expressions of ki67, Bcl-2, caspase-9 and caspase-3 were
tested by Western blotting. Results Down-regulation of SphK1 inhibited cell
proliferation and enhanced apoptosis of RKO cells, expecially after exposed to
DDP. Silence of SphK1 sensitized RKO cells to DDP in a concentration- and time
dependent manner. Cell proliferation of shSphK1 group was obviously reduced
compared with control group or shControl group, and cell apoptosis rate of
shSphK1 group significantly increased compared with control group or shControl
group. Moreover, with the down-regulation of SphK1, the expressions of ki67 and
Bcl-2 were depressed; the expressions of caspase-9 and caspase-3 were raised,
especially after treated with DDP. Conclusion Down-regulation of SphK1 may
decrease the expression of Bcl-2, increase the expressions of caspase-9 and
caspase-3, inhibit cell proliferation, and promote cell apoptosis, thus improving
chemosensitivity of colon cancer RKO cells to DDP.
PMID- 28502301
TI - [Psychological distress promotes proliferation and invasion of glioma by
upregulating lactate deoxygenase A].
AB - Objective To investigate the role of lactate deoxygenase A (LDHA) expression in
the proliferation and invasion of glioma promoted by the psychological distress.
Methods The glioma-bearing nude mice were divided into tumor bearing group,
stress tumor bearing group, negative control, short hairpin RNA (shRNA)-lactate
dehydrogenase A (LDHA) group and shRNA-LDHA stress group. Four weeks after
stress, the tumor size of each group was measured; meanwhile, norepinephrine (NE)
andadrenaline (EPI) in the blood were detected by ELISA; lactic acid in the tumor
tissue was determined by colorimetry. And the expression level of LDHA was
detected by Western blotting. The proliferation of glioma LN229 cells stimulated
by NE was detected by CCK-8 assay and plate clone formation assay; TranswellTM
assay was used to test the invasive ability of LN229 cells. The level of LDHA
mRNA was detected by real-time quantitative PCR. The expressions of LDHA, ERK1/2
and hypoxia-induced factor-1alpha (HIF-1alpha) were observed using Western
blotting. By constructing the reporter gene, we studied the mechanism of LDHA
expression regulated by NE. Results The tumor size and the levels of EPI, NE,
lactic acid and LDHA in the stress group significantly increased as compared with
the tumor bearing group. After silencing LDHA, the proliferation rate and lactate
content decreased. Compared with the control group, the mRNA and protein levels
of LDHA in NE group was significantly elevated; the phosphorylation levels of HIF
1alpha and ERK1/2 was significantly raised; and cell proliferation and invasion
ability were also enhanced. Promoter luciferase reporter assay confirmed that NE
up-regulated the expression of LDHA by HIF-1alpha. Conclusion Adverse
psychological stress can promote the proliferation and invasion of glioma cells
by upregulating LDHA expression.
PMID- 28502302
TI - [Overexpressed miRNA-134b inhibits proliferation and invasion of CD133+ U87
glioma stem cells].
AB - Objective To investigate the role of microRNA-134b (miR-134b) in the
tumorigenesis of glioma stem cells (GSCs) and the possible molecular mechanism.
Methods Real-time quantitative PCR (qRT-PCR) was used to evalate the expression
of miR-134b in CD133+ and CD133- U87 GSCs. A lentiviral vector overexpressing miR
134b in U87 GSCs was constructed, and the effect of miR-134b overexpression on
matrix metalloproteinase-2 (MMP-2), MMP-9 and MMP-12 expressions at both mRNA and
protein levels were detected by qRT-PCR and Western blotting, respectively.
TranswellTM assay was performed to determine the effect of miR-134b
overexpression on GSCs invasion ability. Tumor xenograft models in nude mice were
established to evaluate the effect of miR-134b overexpression on tumorgenesis in
vivo. Results The qRT-PCR showed that, compared with CD133- cells, miR-134b was
significantly down-regulated in CD133+ cells. Cell line over-expressing miR-134b
was successfully established, and miR-134b was up-regulated significantly
compared with empty vector control. Overexpression of miR-134b remarkably
inhibited the invasion of U87 GSCs and the expression of MMP-12. However,
overexpression of miR-134b did not affect MMP-2 and MMP-9 expressions. miR-134b
also suppressed U87 GSCs xenograft growth in vivo. Tumor volume in tumor
xenograft model group was significantly lower than that in control group, and
tumor weight decreased by 42% in the former group. Conclusion Overexpression of
miR-134b inhibits the growth and invasion of CD133+ GSCs.
PMID- 28502303
TI - [Effect of metformin on proliferation and apoptosis of rat prolactinoma MMQ cells
and related mechanisms].
AB - Objective To investigate the effect of metformin on the cell proliferation, cell
cycle and apoptosis of rat prolactinoma MMQ cells in vitro and related molecular
mechanisms. Methods The MMQ cells were treated with 1.25, 2.5, 5, 10, 20 mmol/L
metformin for 48 hours. CCK-8 assay was used to assess the cell proliferation
ability; flow cytometry was used to analyze the cell cycle distribution and
apoptosis; Western blotting was performed to detect the expressions of
AMPKalpha1/2, p-AMPKalpha, mTOR, p-mTOR, insulin like growth factor 1 receptor
(IGF-1R), ERK1/2, p-ERK1/2, AKT, p-AKT, P21, CDK4, cyclin D1, caspase-3, cleaved
caspase-3(c-caspase-3), Bcl-2 and BAX. Results Compared with the control group,
metformin inhibited cell proliferation, induced cell cycle arrest in the G0/G1
phase and promoted cell apoptosis in MMQ cells. The expressions of P21 and c
caspase-3 increased, meanwhile, the expressions of CDK4, cyclin D1, caspase-3 and
Bcl-2 decreased by metformin. Besides, the expression of p-AMPKalpha was
elevated, but p-mTOR was reduced. Furthermore, the expressions of IGF-1R, p-AKT
and p-ERK descended after metformin treatment. Conclusion Metformin could inhibit
cell proliferation, induce cell cycle arrest and apoptosis in MMQ cells by
activating AMPK/mTOR signaling pathway and inhibiting IGF-1R signaling pathway.
PMID- 28502304
TI - [Inula Britannica flower total flavonoids reduces the apoptosis of aging bone
marrow mesenchymal stem cells by anti-oxidation].
AB - Objective To investigate the beneficial effect of Inula Britannica flower total
flavonoids (IBFTF) on aging bone mesenchymal stem cell (BMSC) and its potential
mechanism. Methods The aging BMSCs were induced by D-galactose, and then treated
with 12.5, 25, 50 MUg/mL IBFTF. The cell viability was detected by CCK-8 assay.
The activity of catalase (CAT) and superoxide dismutase (SOD), the content of
malondialdehyde (MDA) and reactive oxygen species (ROS) were measured by a
commercial kit. The apoptosis was assessed by flow cytometry. The protein
expressions of BAX, Bcl-2 and cleaved-caspase-3 (c-caspase-3) were determined by
Western blotting. Results The cell viability and the activity of SOD and CAT in
the aging group decreased significantly compared with the normal group, whereas
different concentrations of IBFTF promoted the cell viability, and simultaneously
increased the activity of SOD and CAT. The apoptosis, the ROS production, the
content of MDA, BAX/Bcl-2 ratio and the protein expression of c-caspase-3 in the
aging group increased obviously compared with the normal group. However, the
treatment of different concentrations of IBFTF reduced the apoptosis, the ROS
production, the content of MDA, BAX/Bcl-2 ratio and the protein expression of c
caspase-3. Conclusion IBFTF can attenuate the apoptosis of aging BMSCs by anti
oxidation.
PMID- 28502305
TI - [Shikimic acid inhibits the degranulation and histamine release in RBL-2H3
cells].
AB - Objective To study the effects of shikimic acid on the proliferation of rat RBL
2H3 cells and the degranulation of the cells induced by C48/80 and its mechanism.
Methods MTT assay was performed to measure the proliferation of RBL-2H3 cells
treated with 3, 10, 30 MUg/mL shikimic acid. Toluidine blue staining was used to
observe the degranulation of RBL-2H3 cells. The release of beta-hexosaminidase
from RBL-2H3 cells treated with 0, 12.5, 25, 50, 80, 100 MUg/mL C48/80 was
determined by substrate assay. ELISA was used to detect the histamine content in
the supernatant of each treated group. Results Shikimic acid at 3, 10, 300 MUg/mL
had no obvious inhibitory effect on the proliferation of RBL-2H3 cells. There was
a dose-effect relationship between the degranulation of RBL-2H3 cells and C48/80
concentration. Shikimic acid inhibited the degranulation of RBL-2H3 cells
compared with the positive control group, the beta-hexosaminidase release rate
and histamine release were significantly reduced in RBL-2H3 cells treated with
shikimic acid and C48/80. Conclusion Shikimic acid can inhibit the degranulation
of RBL-2H3 cells and reduce histamine release.
PMID- 28502306
TI - [Detection and analysis of immune molecules in leukemia cell surfaces of acute
promyelocytic leukemia].
AB - Objective To investigate the immunophenotypic characteristics of acute
promyelocytic leukemia (APL) and its clinical significance. Methods
Immunophenotyping was performed by four-color flow cytometry with CD45/SSC-lin
gating for neoplastic cells and was divided into five levels according to the
intensity of antigen expression. Results The expression intensity and percentage
of typical APL phenotypes were: myeloperoxidase (MPO) and CD33 were consistently
expressed (100%); CD38 (82.35%), CD13 (64.71%), CD64 (50%), CD123 (47.06%) and
CD117 (44.12%) were partially expressed. HLA-DR (97.06%) and CD34 (99.02%) were
negative. Post-chemotherapy remission rate in the Lym+APL patients was
significantly lower than that in the Lym-APL patients. Conclusion The typical
phenotypic characteristics in APL immunophenotyping were high SSC, CD33+ (grade
I), CD38+ (grade I), MPO+ (grade I), CD13+ (grade III), CD64+ (grade I/III),
CD117+ (grade II/III/IV), CD123+ (grade III/IV), CD11b-, HLA-DR-, CD34-.
Understanding of the immunophenotypic features of APL contributes to rapid
diagnosis of APL and the guidance of minimal residual disease (MRD) detection.
PMID- 28502307
TI - [Knock-down of DAB2 interacting protein (DAB2IP) promotes proliferation and
inhibits apoptosis of bladder cancer cells].
AB - Objective To study the expression of DAB2 interacting protein (DAB2IP) in human
bladder cancer tissues and analyze its relationship with pathological grade and
clinical stage, and observe its role in drug resistance of bladder cancer cells.
Methods The expression of DAB2IP in primary and recurrent bladder cancers was
detected by immunohistochemical staining. RNA interference (RNAi) technique was
used to down-regulate the expression of DAB2IP in 5637 and 253J bladder cancer
cells. MTT assay and clone formation assay were performed to test the sensitivity
of cancer cells to pirarubicin. Flow cytometry was done to detect the apoptosis
rate of low-DAB2IP-expressing cells treated with pirarubicin. Results The
expression of DAB2IP was negatively correlated with TNM stage, pathological grade
and lymph node metastasis of bladder cancer. The expression of DAB2IP in the
recurrent bladder cancer was lower than that in the primary bladder cancer. The
low expression of DAB2IP in bladder carcinoma cells was related to drug
resistance. Knock-down of DAB2IP enhanced the colony formation of bladder cancer
cells, reduced the expressions of PARP and caspase-3, increased expressions of
Bcl-2 and Mcl-1, reduced the apoptosis of cancer cells and induced chemotherapy
tolerance. Conclusion Knock-down of DAB2IP can promote the proliferation and
inhibit the apoptosis of bladder cancer cells, and increase the resistance to
chemotherapy.
PMID- 28502308
TI - [Preparation and identification of monoclonal antibody against H1N1 influenza
virus].
AB - Objective To prepare the monoclonal antibody (mAb) against influenza A virus
(H1N1) using purified viral particles as antigen and investigate the
characterization of host cells infected with influenza virus utilizing the mAb.
Methods A/PR/8 (H1N1) virus was cultured in embryonated chicken eggs and further
purified by differential and density gradient centrifugation. The structure of
viral particles was identified by transmission electron microcopy (TEM).
Immunogenicity of purified virus was evaluated by Balb/c mice immunized with
formalin-inactivated virus. Hybridomas secreting mAbs were established through a
fusion of Sp2/0 myeloma cells and splenocytes from the mice immunized with the
virus. The characteristics of mAb were identified by ELISA, immunofluorescence
assay (IFA), Western blotting, hemagglutinin inhibition assay (HI) and
microneutralization assay. The outside hemagglutinin (HA) on the plasma membrane
of the host MDCK cells in which the viruses were propagated and the apoptosis of
MDCK cells infected with the viruses were measured using flow cytometry. Cell
based ELISA was established using mAb specific to HA. Subsequently, the growth of
virus was analyzed by cell-based ELISA. Results Transmission electron microscopy
revealed that the physical structures of the purified virus were spherical,
elliptical and extended threadlike. Serum IgG titer to influenza virus showed a
progressive increase, and the IgG titer reached 106 after the immunization for 6
weeks. Six hybridoma clones secreting mAb specific to A/PR/8 were developed by
hybridoma technology. The HI and neutralization activities of PR8-10 mAb were
significantly higher than those of the other mAbs. HI and neutralization titers
of PR8-10 mAb were 1:2048 and 1:640, respectively. IFA and Western blotting
confirmed that PR8-10 mAb could recognize HA. Flow cytometry showed that PR8-10
mAb also recognized HA on the membrane of MDCK in which the viruses were
replicated and virus infection induced the apoptosis of MDCK cells. Based on the
previous test results that PR8-10 mAb was able to recognize HA on the membrane of
the host cells in which the viruses were replicated, cell-based ELISA we
established was good at analyzing the growth of virus in MDCK cells. Conclusion
We obtained whole viral particles that were demonstrated to be able to stimulate
the production of a high IgG titer in a mouse model with formalin-inactivated
viral particles, and successfully prepared the mAb against H1N1 of high binding
affinity and neutralization potency. HA-specific mAb can be used to analyze the
characteristics of virus infection process and the effect of virus infection on
the host cells as well.
PMID- 28502309
TI - Effects of vitrification of cumulus-enclosed porcine oocytes at the germinal
vesicle stage on cumulus expansion, nuclear progression and cytoplasmic
maturation.
AB - Although offspring have been produced from porcine oocytes vitrified at the
germinal vesicle (GV) stage, the rate of embryo development remains low. In the
present study, nuclear morphology and progression, cumulus expansion, transzonal
projections (TZPs), ATP and glutathione (GSH) levels were compared between
vitrified cumulus-oocyte complexes (COCs) and control COCs (no cryoprotectant
treatment and no cooling), as well as a toxicity control (no cooling).
Vitrification was performed with 17.5% (v/v) ethylene glycol and 17.5% (v/v)
propylene glycol. Vitrification at the GV stage caused premature meiotic
progression, reflected by earlier GV breakdown and untimely attainment of the MII
stage. However, cytoplasmic maturation, investigated by measurement of ATP and
GSH levels, as well as cumulus expansion, proceeded normally despite detectable
damage to TZPs in vitrified COCs. Moreover, treatment with cryoprotectants caused
fragmentation of nucleolus precursor bodies and morphological changes in F-actin
from which oocytes were able to recover during subsequent IVM culture. Reduced
developmental competence may be explained by premature nuclear maturation leading
to oocyte aging, although other mechanisms, such as initiation of apoptosis and
reduction of cytoplasmic mRNA, can also be considered. Further research will be
required to clarify the presence and effects of these phenomena during the
vitrification of immature COCs.
PMID- 28502310
TI - Variations in out-of-pocket costs for primary care services across Australia: a
regional analysis.
AB - The aim of this study is to describe average out-of-pocket costs across different
regions of Australia, as defined by Primary Health Network (PHN) boundaries, and
assess the association between population characteristics and out-of-pocket costs
for selected primary care services. A combination of descriptive and regression
analysis was undertaken using administrative data from the Australian Department
of Human Services reporting on the health services used across PHNs in Australia.
Those in regional areas paid significantly more for Allied Health services than
those in capital cities (A$5.68, P=0.006). The proportion of an area's population
aged 65 years and over was inversely related to out-of-pocket charges for Allied
Mental Health (-A$79.12, P=0.029). Some areas had both high charges and
disadvantaged populations: Country South Australia, Northern Queensland, Country
Western Australia, Tasmania and Northern Territory, or populations with poor
health: Northern Territory and Tasmania. Although there was a large amount of
variation in out-of-pocket charges for primary care services between PHNs in
Australia, there was little evidence of inequality based on health, age and
socioeconomic characteristics of a population or the proportion of Aboriginal and
Torres Strait Islander people.
PMID- 28502312
TI - Sudden Visual Shadow in a 70-Year-Old Man.
PMID- 28502313
TI - Preventing Binge Drinking in Adolescents.
AB - BACKGROUND: In a survey taken in Germany in 2015, 14.1% of the 12- to 17-year
olds surveyed had practiced binge drinking at least once in the preceding 30
days. The school program "Klar bleiben" ("Keep a Clear Head") was designed for
and implemented among 10th graders. The participants committed themselves to
abstain from binge drinking for 9 weeks. We studied whether this intervention
influenced the frequency and intensity of binge drinking. METHODS: This cluster
randomized controlled trial was carried out in 196 classes of 61 schools, with a
total of 4163 participants with a mean age of 15.6 years (standard deviation 0.73
years). Data were collected by questionnaire in late 2015, before the
intervention and again six months later. The primary endpoints were the frequency
of consumption of at least 4 or 5 alcoholic drinks (for girls and boys,
respectively) and the typical quantity consumed. This trial was registered in the
German Clinical Trials Registry (Deutsches Register Klinischer Studien, DRKS)
with the DRKS ID number DRKS00009424. RESULTS: At the beginning of the trial,
there was no difference between the intervention group and the control group with
respect to the primary endpoints. After the intervention, differences were found
among participants who had consumed alcohol before the trial (73.2% of the
overall sample): binge drinking at least once in the preceding month was reported
by 49.4% of the control group and by 44.2% in the intervention group (p = 0.028).
The mean number of alcoholic drinks consumed in each drinking episode was 5.20 in
the control group and 5.01 in the intervention group (p = 0.047). CONCLUSION: The
intervention was effective only in the large subgroup of adolescents who had
previously consumed alcohol: they drank alcohol less often and in smaller amounts
than their counterparts in the control group.
PMID- 28502314
TI - Important Risk Factors Were Not Included.
PMID- 28502315
TI - In Reply.
PMID- 28502311
TI - Tracheotomy-Related Deaths.
AB - BACKGROUND: Tracheotomies are frequently performed on ventilated patients in
intensive care and sometimes lead to fatal complications. In this article, we
discuss the causes and frequency of death associated with open surgical
tracheotomy (OST) and percutaneous dilatational tracheotomy (PDT) on the basis of
a review of the pertinent literature. METHODS: We systematically searched the
PubMed, EMBASE, and Cochrane Library databases and the Karlsruhe Virtual Catalog
for publications (1990-2015) on tracheotomy-related deaths in adults, using the
search terms "tracheotomy" and "tracheostomy." 39 relevant dissertations were
included in the analysis as well. RESULTS: 109 publications were included. Of the
25 056 tracheotomies described, there were 16 827 PDTs and 7934 OSTs; for 295
tracheotomies, the technique used was not stated. 352 deaths were reported,
including 113 in patients treated with PDT, 49 in those treated with OST, and 190
deaths related to a tracheotomy without specification of the method used. The
frequency of death among patients with OST and those treated with PDT was
similar: 0.62% for OST (95% confidence interval [0.47; 0.82]) and 0.67% for PDT
([0.56; 0.81]). The most common causes of death and their frequencies, as a
percentage of all tracheotomies, were hemorrhage (OST: 0.26% [0.17; 0.40], PDT:
0.26% [0.19; 0.35]), loss of airway (OST: 0.21% [0.13; 0.34], PDT: 0.20% [0.14;
0.28]), and false passage (OST: 0.11% [0.06; 0.22], PDT: 0.20% [KI 0.15; 0.29]).
CONCLUSION: Bias in the data cannot be excluded, as these were not epidemiologic
data and the documentation was found to be incomplete. The likelihood of a fatal
complication seems to be the same with both tracheotomy techniques as far as can
be determined from the available evidence. Tracheotomy-related deaths can be
avoided in several ways: by thorough training under the leadership of experienced
physicians, by the use of the World Health Organization's Surgical Safety
Checklist regardless of where the tracheotomy is performed, and by the continuous
vigilance of nursing staff.
PMID- 28502316
TI - Hyponatremia Is a Common Cause.
PMID- 28502317
TI - In Reply.
PMID- 28502318
TI - Look Out-A Trap in the Cardiac Cath Lab.
PMID- 28502319
TI - An unusual case of a young patient with Whipple's disease involving the central
nervous system.
PMID- 28502320
TI - Atypical teratoid rhabdoid tumor arising in a pleomorphic xanthoastrocytoma: a
rare entity.
AB - Atypical teratoid rhabdoid tumor (AT/RT) is a rare and aggressive tumor usually
occurring at younger ages. Pleomorphic xanthoastrocytomas (PXA) on the other hand
are quiescent tumors with benign behavior. AT/RTs arising in the setting of PXA
are exceptional. We present the case of a 23-year-old female patient, the fourth
in the literature, speculated as having AT/RT arising within a PXA, as
demonstrated by the presence of INI1 mutation. The patient presented with a short
history of headache, which increased over time, and emerging seizures. She had a
contrast-enhancing mass in the left temporal area demonstrated by MRI.
Pathological examination demonstrated a dimorphic tumor containing a spindle
pleomorphic component reminiscent of PXA and a rhabdoid component with INI1 loss
showing features of AT/RT. Both components shared the same BRAF mutation,
supporting their common origin, and hence the case was speculated as an AT/RT
arising in the setting of a PXA by secondary genetic change of inactivation of
INI1. She had a poor outcome despite surgery and died 8 months after her
diagnosis.?.
PMID- 28502321
TI - Cytomegalovirus in the human dentate gyrus and its impact on neural progenitor
cells: report of two cases.
AB - Congenital cytomegalovirus (CMV) infection in the 2nd and
3rd trimester results in catastrophic CNS abnormalities. This
susceptibility is thought to result from the high proportion of neural stem cells
in the developing brain. In immunocompromised adults, CNS infection by CMV
preferentially affects ependymal surfaces, from where it expands to involve the
parenchyma. Experimental models of murine CMV infection demonstrate viral tropism
for the dentate gyrus (DG) and subventricular zone, the areas in which adult
neurogenesis occurs. We present two cases of CMV infection of the DG of
immunocompromised allogeneic stem cell transplant recipients. Both cases showed
CMV-positive neurons in the DG granular cell layer, as well as contiguous layers.
The majority of infected cells contained Nissl substance and expressed nestin,
glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), and
neurofilament. These cases demonstrate that CMV infects the DG in humans. Co
expression of nestin and GFAP, indicative of early neurogenesis, is consistent
with experimental models showing neural stem cells as the target of CMV,
providing further histological evidence of neurogenesis in the human dentate.
Finally, the cases suggest that CMV infection produces abnormal migration of
newly formed neurons as evidenced by the finding of virally infected neurons in
the molecular layer of the dentate.?.
PMID- 28502322
TI - High prevalence of elevated molybdenum levels in pediatric CKD patients. A cross
sectional and longitudinal study?.
AB - AIMS: Many of the secondary effects of high levels of molybdenum (Mo) overlap
with symptoms commonly seen in pediatric patients with chronic kidney disease
(CKD). We measured plasma Mo levels and examined the relationship between Mo
levels and kidney function. MATERIALS AND METHODS: The study was carried out at
the London Health Sciences Centre in London, Ontario, Canada with 36 children and
adolescents 4 - 18 years of age with CKD. There were 1 - 6 trace element
measurements (Mo and copper (Cu)) per patient. We studied the proportion of
patients with abnormal trace element levels and the relationship between trace
element levels and estimated glomerular filtration rate (eGFR), calculated using
the Filler formula. Plasma Mo and Cu levels were measured using High Resolution
Sector Field Inductively Coupled Mass Spectrometry. Anthropomorphic data and
blood parameters were collected from our electronic chart program. RESULTS:
Median eGFR was 51 mL/min/1.73m2 (35, 75). Median Mo level was 2.00
ug/L (1.40, 2.88). 20 patients had at least one set of Mo levels above the
published reference interval in either unit, and the results of 46% of the tests
were above the interval. There was a strong negative correlation between the Mo
levels and the eGFR (Spearman's r = -0.627, p < 0.0001). CONCLUSIONS: Our study
suggests that pediatric patients with CKD have elevated plasma levels of Mo,
which may cause secondary effects commonly associated with CKD. The elevated Mo
levels in our center's catchment area may cause an accumulation of this trace
element in patients with impaired renal function.?.
PMID- 28502323
TI - A case report on the exceptional coincidence of two inherited renal disorders:
ADPKD and Alport syndrome?.
AB - Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic
cause of dialysis-requiring end-stage renal disease in adults and is
characterized by the slowly progressing replacement of renal tissue by focal
macrocysts. Alport syndrome (AS; hereditary nephritis) is a rare, inherited
disorder of the basement membrane associated with hematuria, proteinuria, and
loss of kidney function as well as sensorineural hearing loss and ocular
abnormalities. Here, we report on a family in which both ADPKD and AS are
present. In a male patient, both -ADPKD and AS coincided. This patient shows the
very rare coexistence of two severe, inherited renal disorders and illustrates
the importance of considering additional diagnoses in the setting of positive
family history for a common hereditary disorder.?.
PMID- 28502324
TI - Favorable long-term outcomes of isolated liver transplantation in a child with
atypical hemolytic uremic syndrome caused by a novel complement factor H
mutation?.
AB - Atypical hemolytic uremic syndrome (aHUS) is a rare syndrome characterized by
microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury that
is usually caused by complement dysregulation. Complement factor H (CFH) is a
regulator of the complement system produced in the liver, and CFH gene mutations
are the most frequent causes of aHUS. To date, the therapeutic options for aHUS
with CFH mutations have consisted of plasma infusions, plasma exchange, kidney
transplantation, isolated liver transplantation, or combined liver and kidney
transplantation. Recently, eculizumab, a humanized monoclonal antibody directed
against complement C5, has been proven to be effective against aHUS. However,
life-long eculizumab maintenance therapy is usually required for aHUS; therefore,
other curative options should be considered. We describe a case of neonatal onset
aHUS caused by a novel mutation of CFH and treated with an isolated liver
transplantation at the age of 24 months. Nearly 5 years post-transplant, the
patient's health has been generally good without evidence of aHUS. This case
report suggests that isolated liver transplantation in aHUS patients with CFH
mutations and preserved eGFR could be a curative therapeutic option in contrast
to long-term eculizumab therapy.?.
PMID- 28502325
TI - Long-term Mortality in Hospitalized Patients With Community-Acquired Pneumonia.
PMID- 28502326
TI - K+ and Mg2+ Dyshomeostasis in Acute Hyperadrenergic Stressor States.
AB - Acute stressor states are linked to neurohormonal activation that includes the
adrenergic nervous system. Elevations in circulating epinephrine and
norepinephrine unmask an interdependency that exists between K+ and Mg2+ based on
their regulation of a large number of Mg2+-dependent Na+-K+-ATPase pumps present
in skeletal muscle. The hyperadrenergic state accounts for a sudden translocation
of cations into muscle with the rapid appearance of hypokalemia and
hypomagnesemia. The resultant hypokalemia and hypomagnesemia will cause a delay
in myocardial repolarization and electrocardiographic QTc prolongation raising
the propensity for supraventricular and ventricular arrhythmias. In this review,
we focus on the interdependency between K+ and Mg2+, which is clinically relevant
to acute hyperadrenergic stressor states found in patients admitted to intensive
care units.
PMID- 28502327
TI - Fanconi Anemia and Laron Syndrome.
AB - BACKGROUND: Fanconi anemia (FA) is a condition characterized by genetic
instability and short stature, which is due to growth hormone (GH) deficiency in
most cases. However, no apparent relationships have been identified between FA
complementation group genes and GH. In this study, we thereby considered an
association between FA and Laron syndrome (LS) (insulin-like growth factor 1 [IGF
1] deficiency). METHODS: A 21-year-old female Mexican patient with a genetic
diagnosis of FA was referred to our research department for an evaluation of her
short stature. Upon admission to our facility, her phenotype led to a suspicion
of LS; accordingly, serum levels of IGF-1 and IGF binding protein 3 were analyzed
and a GH stimulation test was performed. In addition, we used a next-generation
sequencing approach for a molecular evaluation of FA disease-causing mutations
and genes involved in the GH-IGF signaling pathway. RESULTS: Tests revealed low
levels of IGF-1 and IGF binding protein 3 that remained within normal ranges, as
well as a lack of response to GH stimulation. Sequencing confirmed a defect in
the GH receptor signaling pathway. CONCLUSIONS: To the best of our knowledge,
this study is the first to suggest an association between FA and LS. We propose
that IGF-1 administration might improve some FA complications and functions based
upon IGF-1 beneficial actions observed in animal, cell and indirect clinical
models: erythropoiesis modulation, immune function improvement and metabolic
regulation.
PMID- 28502328
TI - The Association Between Endocan Levels and Subclinical Atherosclerosis in
Patients With Type 2 Diabetes Mellitus.
AB - BACKGROUND: Proinflammatory conditions induced by circulating factors in diabetes
play a pivotal role in endothelial dysfunction and related vascular
complications. Endothelial cell-specific molecule-1 or endocan is a dermatan
sulfate proteoglycan secreted primarily by the vascular endothelium. Although
endocan has been shown to be a potential biomarker in coronary heart disease, its
role in the pathogenesis of atherosclerosis (AS) in diabetes remains unclear. In
this study, we investigated the correlation between serum endocan levels and
subclinical AS in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND
METHODS: Patients (n = 69) with T2DM were included. All the patients were
stratified based on the absence (n = 42) or presence (n = 27) of subclinical AS.
Healthy subjects (n = 28) served as controls. Serum levels of endocan, fasting
blood glucose, glycosylated hemoglobin A1, high-sensitivity C-reactive protein
and carotid intima-media thickness (cIMT) were measured. RESULTS: Endocan levels
were significantly elevated in both the T2DM (0.89 +/- 0.28ng/mL) and T2DM with
subclinical AS (1.20 +/- 0.33ng/mL) groups relative to the control group (0.68 +/
0.24ng/mL) (P < 0.05 for all). Endocan levels were also positively correlated
with glycosylated hemoglobin A1, fasting blood glucose and cIMT (r = 0.292, P =
0.004; r = 0.224, P = 0.027 and r = 0.496, P < 0.001, respectively). In addition,
endocan levels were independently associated with cIMT (beta = 0.220, t = 5.816,
P = 0.000) and were a significant risk factor for T2DM with subclinical AS (odds
ratio = 1.98, 95% CI: 1.43-2.73, P < 0.001). CONCLUSIONS: These findings suggest
that serum endocan levels may be a useful biomarker for the early diagnosis of
subclinical AS in patients with T2DM.
PMID- 28502329
TI - Serum Adipocytokine Levels as Surrogate Markers for Disease Activity of Crohn's
Disease.
AB - BACKGROUND: Determining inflammatory activity is crucial for assessing disease
activity and for tailoring therapy in patients with Crohn's disease (CD). This
study aimed to evaluate adipocytokine levels in patients with CD and to determine
whether they can serve as surrogate markers for disease activity. MATERIALS AND
METHODS: Serum samples and information regarding the clinical features of
patients in the CD Network Project registry were collected from March 2009 to
February 2012. Patients with CD and disease duration of at least 2 years were
enrolled in this study. Fasting serum leptin, adiponectin, obestatin and ghrelin
levels were measured, and their correlation with clinical features of the
patients was analyzed. Serum adipocytokine levels were evaluated according to
disease activity as determined by CD activity index score. RESULTS: A total of
153 patients with CD were included. Serum ghrelin levels negatively correlated
with patient age (P = 0.041) and age at diagnosis (P = 0.017), and positively
correlated with C-reactive protein (CRP) levels (P = 0.017). Multiple regression
analysis showed that serum ghrelin levels were related only to CRP levels (P =
0.032). Like ghrelin, serum leptin levels were also related to CRP levels (P <
0.001). Obestatin and adiponectin levels were not related to CRP levels. Serum
adipocytokine levels did not significantly differ across different disease
locations or behaviors. Serum ghrelin levels were significantly lower in patients
with CD with a history of surgery than in those without (P = 0.007). CONCLUSIONS:
Serum ghrelin and leptin levels may be useful as surrogate markers for disease
activity in patients with CD.
PMID- 28502330
TI - Three Decades of Follow-up of Adults After Recovery From Invasive Pneumococcal
Pneumonia.
AB - BACKGROUND: Streptococcus pneumoniae infection is the most common cause of
community-acquired pneumonia in adults. Invasive pneumococcal disease (IPD)
carries a high case fatality rate. We investigated the lifespan of adults who
recovered from IPD during a 32-year follow-up. MATERIALS AND METHODS: We
determined whether adults discharged after an episode of IPD from hospitals
affiliated with the Marshall University Joan C. Edwards School of Medicine in
Huntington, West Virginia from 1983-2003 were alive on June 30, 2014. Lifespan
was assessed by Kaplan-Meier methodology, Cox proportional hazards multivariate
analysis, life expectancy using life tables for West Virginia, years of potential
life lost and serotype occurrence. RESULTS: The study group comprised 155 adults
who survived IPD. They had a mean age at discharge of 64.6 years, mean lifespan
after IPD of 7.1 years, mean expected lifespan after IPD of 17.0 years, mean age
at death of 71.6 years and a mean life expectancy of 81.6 years. Only 14 (9.0%)
patients lived longer than their life expectancy. Of the 13 comorbid diseases
analyzed, cancer and neurologic diseases and the number of comorbid diseases
suffered by each patient were the significant variables associated with survival.
The mean years of potential life lost was 9.936 years. Only serotype 12 of 31
serotypes recovered occurred more often in patients who survived for 11 or more
years after discharge (relative risk = 3.44, 95% CI: 1.19-9.95). CONCLUSIONS: The
fact that most adult patients who recovered from IPD died before their documented
life expectancy argues for the pernicious severity of IPD and the importance of
immunization of adults with pneumococcal vaccines.
PMID- 28502331
TI - Risk Factors and Outcomes of Acute Kidney Injury in Patients With Hepatitis B
Virus-Related Acute-on-Chronic Liver Failure.
AB - BACKGROUND: Acute kidney injury (AKI) is common in patients with hepatitis B
virus (HBV)-related acute-on-chronic liver failure (ACLF); however, few studies
concerning the risk factors and recovery patterns of renal function have been
published. MATERIALS AND METHODS: A retrospective analysis of 150 patients with
HBV-ACLF was performed. The occurrence, risk factors and functional recovery of
AKI among patients with HBV-ACLF were investigated. RESULTS: A total of 90
patients (60%) with HBV-ACLF developed AKI. Patients with AKI had higher creatine
kinase (P = 0.004), total bilirubin (P = 0.039), HBV viral load (P = 0.044),
serum creatine (P < 0.001) and model for end-stage liver disease (MELD) score (P
< 0.001) values and a higher proportion of hepatic encephalopathy (P = 0.032) and
spontaneous bacterial peritonitis (SBP) (P = 0.042) than patients without AKI.
Logistic regression analysis illustrated that SBP (odds ratio = 6.214, P = 0.012)
and MELD score (odds ratio = 1.097, P = 0.006) were risk factors for the
development of AKI. A subgroup analysis of recovery patterns in renal function
showed that patients with a severe AKI stage had worse outcomes (P = 0.007). The
proportion of patients who experienced a complete recovery was higher in
survivors than in the overall AKI populations (P = 0.004). Follow-up studies
showed that the no-AKI group had a higher transplant-free survival rate than the
AKI group at day 90 (80.0% versus 26.7%, respectively, P < 0.001). The survival
rate among patients with AKI Stage 1 was higher than that of patients with AKI
Stage 2 and patients with AKI Stage 3 (P < 0.001). CONCLUSIONS: AKI is common in
patients with HBV-ACLF. The SBP and MELD score have some prognosis value for
patients with AKI. AKI and its stages affect the 90-day transplant-free mortality
rate. It is important to focus on exploring the early recognition of AKI and
early intervention of those risk factors in individuals with HBV-ACLF.
PMID- 28502333
TI - Zika Virus: Epidemiology, Pathogenesis and Human Disease.
AB - The Zika virus is a positive sense, single-stranded RNA arbovirus in the
Flaviviridae family, genus Flavivirus. This virus was initially isolated in
Africa and is transmitted to nonhuman primates and humans by mosquitoes. Initial
reports describe sporadic mild viral infection with fever, arthralgia, myalgia
and conjunctivitis in Africa and Asia. However, its geographic distribution has
significantly increased, and it has caused large outbreaks in the Yap Islands in
2007, in French Polynesia in 2013 and in Brazil in 2015. Multiple cases of
Guillain-Barre' syndrome occurred in French Polynesia and Columbia during
outbreaks, and infections in pregnant women in Brazil have been associated with
microcephaly and fetal loss. The viremic phase in humans is short, and diagnosis
usually depends on positive immunoglobulin M titers with serum neutralization
tests for confirmation. Treatment is directed at symptoms; there are no antiviral
drugs available. Transmission can also occur through sexual contact with infected
men and through blood transfusion. Prevention is important in women and includes
limiting travel to endemic areas when possible, control of mosquito populations
and condom use when appropriate. The Centers for Disease Control and Prevention
is actively involved in tracking these infections and providing up-to-date
information.
PMID- 28502332
TI - The Enhanced International Prognostic Index for Diffuse Large B-cell Lymphoma.
AB - OBJECTIVE: To explore the prognostic value of the enhanced International
Prognostic Index (NCCN-IPI) for Asian patients with diffuse large B-cell lymphoma
(DLBCL) treated in the rituximab era. MATERIALS AND METHODS: We performed a
retrospective analysis of 176 patients with newly diagnosed DLBCL. The estimated
overall survival (OS) and progression-free survival (PFS) of the different risk
groups were discriminated by the International Prognostic Index (IPI), the
revised International Prognostic Index (R-IPI) and the NCCN-IPI. RESULTS: With a
median follow-up of 18 months, at 3 years, the OS was 73% and the PFS was 65%.
The 3-year OS for the 4 NCCN-IPI risk groups were 91% versus 80% versus 57%
versus 45% (P < 0.001); the 3-year PFS were 77% versus 72% versus 56% versus 26%
(P < 0.001). The 3-year OS of the 4 risk groups discriminated by the IPI ranged
from 85-55% (P < 0.001); the 3-year PFS ranged from 81-41% (P < 0.001). The 3
year OS of the 3 distinct prognostic groups by the R-IPI ranged from 86-51% (P <
0.001); the 3-year PFS ranged from 86-47% (P < 0.001). The 3-year OS and PFS of
the high-risk group according to the NCCN-IPI were lower than the IPI and R-IPI.
Using the NCCN-IPI, the outcomes among the risk groups spanned a large range, and
the survival of the high-risk group was significantly different from the high
intermediate risk group. CONCLUSIONS: The NCCN-IPI is a clinically useful
prognostic index for patients with DLBCL treated in the rituximab era, especially
for high-risk patients.
PMID- 28502334
TI - AP-1 Expression and its Clinical Relevance in Immune Disorders and Cancer.
AB - The inflammatory response is known to have a significant role in certain
autoimmune diseases and malignancies. We review current knowledge regarding the
functions of activator protein 1 (AP-1) as an important modulator in several
immune disorders and carcinomas. AP-1 is overexpressed in rheumatoid arthritis
and in long-term allogeneic hematopoietic stem cell transplantation survivors;
however, decreased expression of AP-1 has been observed in psoriasis, systematic
lupus erythematosus and in patients who do not survive after hematopoietic stem
cell transplantation. AP-1 also is implicated in the control of various cancer
cells. Higher levels of AP-1 components are present in breast and endometrial
carcinomas, colorectal cancer and in acute myeloid leukemia, Hodgkin's lymphoma
and anaplastic large cell lymphoma, with downregulation in ovarian and gastric
carcinomas and in patients with chronic myelogenous leukemia. AP-1 may enable the
development of helpful markers to identify early-stage disease or to predict
severity.
PMID- 28502335
TI - Limb-Girdle Muscular Dystrophy 2B and Miyoshi Presentations of Dysferlinopathy.
AB - We report the following 2 subtypes of progressive limb-girdle dystrophy type 2B:
limb-girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi. The first patient
described had weakness in the anterior thigh muscles (LGMD2B) and the second
patient had calf muscle weakness and atrophy (Miyoshi). Literature review was
performed and LGMD2B was compared and distinguished from other myopathies of
similar nature. Genetic testing with polymerase chain reaction analysis of the
DYSF gene confirmed the diagnosis in both patients. Additional findings of
histopathology, specific stain for sarcolemmal membrane protein, Western blot
analysis and clinical presentation clinched the diagnosis further of
dysferlinopathy (LGMD2B) in both our patients. Currently, there is no definitive
treatment on the horizon and immunosuppressive therapy is not recommended for
this condition. Gene therapy may have a future role, but at present, muscle
strengthening exercises and patient awareness are the mainstays.
PMID- 28502336
TI - Silicone Injection-Related Granulomatous Hypercalcemia.
AB - Cosmetic filler injections are known to cause a number of acute and chronic
effects, including local inflammation, nodule formation and granulomatous
reaction. The timeline of these events is highly variable, occurring from hours
to decades following injection. In few cases, systemic effects have been
observed. We report a case of granulomatous disease secondary to illicit silicone
injection causing recalcitrant hypercalcemia. Additionally, we review the
pathophysiology of inflammation in cosmetic filler injections, the prevailing
understanding of hypercalcemia in granulomatous disease and summarize the most
effective treatment modalities for this rare condition.
PMID- 28502337
TI - Successful Treatment of Central Nervous System Vasculitis Associated with
Relapsing Polychondritis With Cyclophosphamide.
PMID- 28502338
TI - Diabetes as First Manifestation of Autoimmune Pancreatitis.
PMID- 28502339
TI - Atypical Common Carotid Artery Diaphragm With an Accompanying Aneurysm.
PMID- 28502340
TI - Glossodynia After Osteoporosis Treatment.
PMID- 28502341
TI - Cigar-Shaped Intramuscular Calcifications.
PMID- 28502343
TI - Intrathymic Parathyroid Adenoma.
PMID- 28502342
TI - Emphysematous Pyelitis: An Entity Distinct from Emphysematous Pyelonephritis.
PMID- 28502344
TI - Cement Pulmonary Embolism.
PMID- 28502346
TI - Kinematics and Function of Total Ankle Replacements Versus Normal Ankles.
AB - End-stage ankle arthritis produces severe functional disability, quantifiable by
gait abnormalities. In all categories of gait parameters, total ankle
arthroplasty (TAA) satistically significantly improves function, compared to
patients' preoperative function. There are increases in step length, cadence and
velocity; in sagittal plane motion of the ankle, as well has hip and knee motion,
and in ankle power and moment. These functional gait improvements correspond to
clinical improvements of pain relief and satisfaction. Although these
improvements fail to reach the functional performance of healthy controls, the
improvement over preoperative function is clinically meaningful and statistically
significant.
PMID- 28502345
TI - An Intriguing Case of Purple Urine Bag Syndrome.
PMID- 28502347
TI - Ankle Arthrodesis Versus Total Ankle Arthroplasty.
AB - Reoperation rates are higher in total ankle arthroplasties (TAAs) compared with
ankle arthrodesis. Infection rates for primary TAAs are 1.4% to 2.4%. The
survival rate of TAA is approximately 75% to 90% at 10 years. Arc of motion is
maintained with TAAs compared with ankle arthrodesis. Ankle arthrodesis increases
arc of motion through the talonavicular joint. Several factors are strong reasons
to favor ankle fusion rather than TAA. TAA and ankle arthrodesis are effective
treatments of end-stage ankle arthritis but the choice must be tailored to
individual patients.
PMID- 28502348
TI - Osteolysis in Total Ankle Replacement: How Does It Work?
AB - Aseptic loosening of implants remains the most common reason for revision surgery
for hip, knee, or ankle prostheses. Although a great scientific effort has been
made to explain the underlying mechanisms it remains poorly understood, complex,
and multifactorial. Many factors, including age, body weight, activity lesions,
implant design, fixation methods, material proprieties, immunologic responses,
and biomechanical adaptations to total ankle replacement all contribute to the
development of periprosthetic osteolysis.
PMID- 28502349
TI - Total Ankle Replacement in the Presence of Talar Varus or Valgus Deformities.
AB - Patients presenting with end-stage ankle arthritis with coronal plane talar
deformities have a variety of complex multidirectional deformities that require
careful preoperative assessment and a clear understanding of the pathophysiology.
Surgeons managing these patients with total ankle arthroplasty need to be
familiar with extra-articular and intra-articular surgical methods to correct pes
planus and pes cavus deformities, including bony procedures and soft tissue
procedures. Performing these procedures in 1 or 2 stages depends on surgeon
preference and the severity of the deformities. This article recommends a two
staged reconstruction for more severely deformed feet.
PMID- 28502350
TI - Current Update in Total Ankle Arthroplasty: Salvage of the Failed Total Ankle
Arthroplasty with Anterior Translation of the Talus.
AB - Ankle replacement results may be compromised by malposition of the components. An
anterior displacement can be measured on a lateral standing radiograph. The ankle
may appear anteriorly translated because the ankle is overstuffed, the heel cord
is tight, or the posterior capsule is tight. In ankle instability with
degenerative arthritis, the talus may be anteriorly translated, internally
rotated, and in varus. In an ankle replacement, this deformity may persist and
will require correction. On occasion, the talus is inserted too anterior;
revision to a flat cut talar component and posterior translation of the talar
component will result in correction.
PMID- 28502351
TI - Malalignment Correction of the Lower Limb Before, During, and After Total Ankle
Arthroplasty.
AB - One of the main challenges in ankle replacement is correction of any deformities
in the operative limb. Deformity can be found proximal and distal to the ankle
joint as well as in the ankle joint. There are static and dynamic deformities
that can create unbalanced ankle joints causing early and often catastrophic
failure. Surgeons must recognize the deformities that are present and use sound
judgment to balance the ankle joint with procedures before, during, or after
total ankle implantation. This article helps clinicians to identify deformity and
provides a basic template to consider how to address each challenge.
PMID- 28502352
TI - Revision of Stemmed Agility Implants.
AB - Total ankle arthroplasty has advanced rapidly in the last 20 years. Early agility
implants enjoyed improved survivability compared with more archaic total ankle
implants. When talar subsidence occurs, the revision options include a stemmed
component to improve stability by spanning the subtalar joint. Removal and
revision of these stemmed components can be difficult because of ingrowth and
bone loss.
PMID- 28502353
TI - Management of Talar Component Subsidence.
AB - Component subsidence has been found to be the top complication that leads to
failure of the total ankle arthroplasty (TAA). The cause of subsidence formation
is unclear, and is multifactorial. Talar subsidence is more frequently met than
tibial subsidence, and the subsequent big bone loss is demanding to handle. As a
revision treatment option, neither a revision TAA nor a salvage ankle and/or
hindfoot arthrodesis procedure is easy to perform or can obtain a definite
outcome. The Salto XT can be used to treat most of the TAA systems available for
use in the United States with acceptable short-term outcomes.
PMID- 28502354
TI - Soft Tissue Reconstruction After Total Ankle Arthroplasty.
AB - Wound complications following total ankle replacement are common. A team
approach, including plastic surgeons, should be utilized to manage these wound
issues. The handling of the wound, from the index procedure, to a variety of
flaps, can be utilized to provide a successful outcome following an ankle
replacement.
PMID- 28502355
TI - How To Diagnose and Treat Infection in Total Ankle Arthroplasty.
AB - Periprosthetic infection after total ankle arthroplasty (TAA) is a serious
complication, often requiring revision surgery, including revision arthroplasty,
conversion to ankle arthrodesis, or even amputation. Risk factors for
periprosthetic ankle infection include prior surgery at the site of infection,
low functional preoperative score, diabetes, and wound healing problems. The
clinical presentation of patients with periprosthetic ankle joint infection can
be variable and dependent on infection manifestation: acute versus chronic. The
initial evaluation in patients with suspected periprosthetic joint infections
should include blood tests: C-reactive protein and erythrocyte sedimentation
rate. Joint aspiration and synovial fluid analysis can help confirm suspected
periprosthetic ankle infection.
PMID- 28502356
TI - Dealing with the Stiff Ankle: Preoperative and Late Occurrence.
AB - In patients with a stiff ankle replacement, appropriate resection of scarred
capsular structures, hypertrophic bone debridement, and careful release of
tendons should be performed to achieve good outcomes. Appropriately sized and
correctly implanted components are required to restore ankle function to as
normal as possible. Although not proven, the better a total ankle replacement is
balanced, the less likely scar and heterotopic bone formation will occur. In
patients with a stiff and painful ankle replacement, a preoperative diagnostic
workup is mandatory to understand the underlying pathologic process and plan
appropriate treatment. All underlying causes should be addressed.
PMID- 28502357
TI - Experience with Navigation in Total Ankle Arthroplasty. Is It Worth the Cost?
AB - Optimal placement of correctly sized total ankle replacement (TAR) implants is
elemental to prolonging the working life. The negative mechanical effects of
implant malalignment are well characterized. There is one FDA-approved navigated
TAR system with limited but encouraging outcomes data. Therefore, its value can
be estimated only based on benefits other than a proven clinical outcomes
improvement over conventional systems. These include unique preoperative planning
through 3-dimensional templating and virtual surgery and the patient-specific cut
guides, which also reduce overall instrumentation needed for the case. To better
inform this conversation, well-observed longitudinal outcomes studies are
warranted.
PMID- 28502358
TI - Is There Anything to Learn from a National Joint Registry?
AB - National joint registries (NJRs) have been established in Northern Europe for
over 20 years. Since then, many other countries have begun collecting and
reporting national data for total ankle arthroplasty (TAA). With relatively small
numbers implanted, a large variety of available designs, and with any long-term
reports dominated by designer groups, TAA is ideally placed to benefit from large
national or even pooled national registries. This article reviews the existing
registry-based literature with respect to what is already known. The potential
positives and down sides of registry data also are highlighted.
PMID- 28502359
TI - Pearls and Pitfalls for a Surgeon New to Ankle Replacements.
AB - The role of the surgeon learning curve in total ankle replacement (TAR) has
produced contradictory results. It is important for a new surgeon to know what
clinical and radiological parameters are considered reliable and ideal. It is
clear that exposure to a high-volume center will increase the reliability of a
new surgeon approaching TAR. Implant choice may be influenced by surgeon
training, and the debate of mobile versus fix-bearing prosthesis is still open.
Anterior versus lateral approach is still an open debate, with any hypothetical
advantages given by the direct vision on the center of rotation to be proven.
PMID- 28502360
TI - Preface.
PMID- 28502361
TI - Measuring and accounting for the Hawthorne effect during a direct overt
observational study of intensive care unit nurses.
AB - BACKGROUND: Because suspecting nurses could alter hand hygiene (HH) behavior when
observed, the goal of this article was to describe how the Hawthorne effect (HE)
was measured and accounted for in a direct observational prospective study.
METHODS: Observations were made 8 h/d for 3-5 days in 5 intensive care units
(ICUs) (4 hospitals) on a convenience sample of 64 ICU nurses in Texas. The HE
was measured so if hand hygiene adherence rates of the first 2 hours were 20%
higher than the last 6 hours, the first 2 hours would be dropped and an
additional 2 hours would be added at the end of the observation period. Hourly
rates were recorded during the observation period, using room entry and room
exit. RESULTS: The difference between aggregated rates of the first 2 hours and
last 6 hours was 0.56% (range, 0.02%-15.74%) and not significant. On 12
observation days, higher rates were observed during the first 2 hours. On 6 days,
higher rates were observed in the last 6 hours, with difference in rates of 1.43%
(day 1), 2.97% (day 2), and 1.42% (day 3). CONCLUSIONS: The attempt at measuring
and accounting for the HE showed little difference in HH rates throughout the
observation period. Based on these results, necessity of the observer moving
locations during HH surveillance after 10-20 minutes, because of a feared HE,
might not be necessary.
PMID- 28502362
TI - [When to start, how to manage and when to stop non-invasive ventilation during
acute COPD exacerbation?]
PMID- 28502363
TI - [Weaning from mechanical ventilation. Role of conventional methods and non
invasive ventilation for weaning].
PMID- 28502364
TI - [Which inhaled pharmacological treatments for COPD acute exacerbations in
hospital?]
PMID- 28502365
TI - [Tracheotomy and high-flow oxygen therapy for mechanical ventilation weaning].
PMID- 28502366
TI - [Management of inpatients with acute COPD exacerbation. When to indicate
mechanical ventilation?]
PMID- 28502367
TI - [Antibiotics for acute exacerbation in hospitalized COPD patients].
PMID- 28502369
TI - [Oxygen therapy for acute COPD exacerbations].
PMID- 28502368
TI - [What is the role of non-inhaled drug management in acute COPD exacerbation?]
PMID- 28502370
TI - [Differential diagnosis of acute COPD exacerbations].
PMID- 28502371
TI - Decreased clinic visits for acute respiratory infections following an adult
tonsillectomy: A population-based study.
AB - PURPOSE: This study attempted to investigate the effects of a tonsillectomy on
utilization of medical resources for acute respiratory infections by comparing
numbers and costs of clinic visits within 1year before and after a tonsillectomy.
MATERIALS AND METHODS: Data for this study were retrieved from the Taiwan
Longitudinal Health Insurance Database 2005. The study includes 481 patients aged
18-80years who underwent a tonsillectomy and 481 comparison patients. A
multivariate regression model employing difference-in-difference was carried out
to assess the independent association between a tonsillectomy and the number and
costs of clinic visits. RESULTS: We found that for patients who underwent a
tonsillectomy, the mean number of clinic visits for acute respiratory care 1year
before and after the index date significantly decreased from 7.3 to 4.2
(p<0.001). However, for the comparison group, there was no significant difference
in the number (p=0.540) or costs (p=0.221) of clinic visits for acute respiratory
care 1year before and after the index date. A multivariate regression model
revealed that a tonsillectomy was associated with a reduction of 3.38 in the mean
number of clinic visits for acute respiratory care (p<0.001). In other words, a
tonsillectomy reduced by 46.3% (3.38/7.3) the number of clinic visits for acute
respiratory care after adjusting for sociodemographic characteristics and medical
comorbidities compared to comparison patients. CONCLUSIONS: This study
demonstrated that a tonsillectomy was of substantial benefit to adult patients in
that it provides decreased healthcare utilization for acute respiratory
infections.
PMID- 28502373
TI - [The oral cavity: A mirror of diabetes].
AB - Diabetes and the oral cavity are closely associated as diabetes physiopathology
affects the mouth and the oral manifestations are numerous and varied. These need
to be searched systematically at every clinical examination as they are not only
comorbidity factors but also have a two-way relationship with diabetes control.
Periodontal diseases are the most frequent pathologies and the relationship with
glycemic control has clearly been established: their frequency increases in case
of uncontrolled glycemia, which makes them a good marker of glycated hemoglobin.
Thorough oral health follow-up of diabetic patients that is coordinated by its
various actors from the beginning of the treatment is thus of great interest.
Most of the care given to diabetic patients can easily be performed at the dental
clinic, provided adequate precautions are taken and improvement of the oral
cavity is beneficial to glycemic control as well as to the patients' quality of
life. When implemented by trained oral health professionals in dental clinics,
therapeutic education proves highly efficient.
PMID- 28502376
TI - [2016 European Society of Cardiology guidelines for the management of
dyslipidemias].
AB - Cardiovascular risk evaluation is a fundamental approach in cardiovascular
prevention. Cardiovascular risk categories are associated with lipid-lowering
drug intensity. LDL cholesterol is the main target of treatment. Statins are the
first line lipid-lowering drugs. Lipid-lowering combination therapy is to be used
in order to obtain the LDL cholesterol targets. Screening of familial
hypercholesterolemia might be included in all prevention population strategy.
PMID- 28502374
TI - [Severe membranoproliferative glomerulonephritis with polyadenopathy associated
with hypocomplementemic urticarial vasculitis syndrome].
PMID- 28502372
TI - Early-Onset Acute Recurrent and Chronic Pancreatitis Is Associated with PRSS1 or
CTRC Gene Mutations.
AB - OBJECTIVES: To assess whether the age of onset was associated with unique
features or disease course in pediatric acute recurrent pancreatitis (ARP) or
chronic pancreatitis (CP). STUDY DESIGN: Demographic and clinical information on
children with ARP or CP was collected at INSPPIRE (INternational Study Group of
Pediatric Pancreatitis: In Search for a CuRE) centers. The Cochran-Armitage trend
test and Jonckheere-Terpstra test were used to examine for differences between
pediatric age groups (<6, 6-11, and >=12 years). RESULTS: Between September 2012
and March 2016, 342 children with ARP or CP were enrolled; 129 (38%) were <6
years of age at the time of first diagnosis of acute pancreatitis, 111 (32%) were
6-11 years of age, and 102 (30%) were >=12 years of age. Early-onset disease was
associated with mutations in cationic trypsinogen (PRSS1) (P < .01), chymotrypsin
C (CTRC) (P = .01), family history of acute pancreatitis (P = .02), family
history of CP (P < .01), biliary cysts (P = .04), or chronic renal failure (P =
.02). Later-onset disease was more commonly present with hypertriglyceridemia (P
= .04), ulcerative colitis (P = .02), autoimmune diseases (P < .0001), or
medication use (P < .01). Children with later-onset disease also were more likely
to visit the emergency department (P < .05) or have diabetes (P < .01).
CONCLUSIONS: Early-onset pancreatitis is associated strongly with PRSS1 or CTRC
mutations and family history of pancreatitis. Children with later-onset disease
are more likely to have nongenetic risk factors. Future studies are needed to
investigate whether the disease course, response to therapy, or clinical outcomes
differ relative to the timing of disease onset.
PMID- 28502375
TI - [Pyomyositis associated with reactive arthritis].
PMID- 28502377
TI - Long-term follow-up of patients undergoing autologous noncultured melanocyte
keratinocyte transplantation for vitiligo and other leukodermas.
AB - BACKGROUND: Persistence of pigmentation after a melanocyte-keratinocyte
transplantation procedure (MKTP) is an important consideration for efficacy.
OBJECTIVE: We sought to determine long-term repigmentation of MKTP in vitiligo
and other leukodermas. METHODS: A retrospective review of electronic medical
records was conducted for all MKTPs performed at Henry Ford Hospital between
January 2009 and April 2014. Repigmentation was assessed by a 5-point grading
scale (poor to excellent) and Vitiligo Area Scoring Index (VASI). RESULTS: One
hundred patients had MKTP performed at 236 anatomically-based lesions (ABLs); 63
patients with 157 ABLs had long-term data available (12-72 months; median, 24
months). Segmental vitiligo, nonsegmental vitiligo, and physical leukoderma
demonstrated improvement in VASI scores: -75.6 +/- 24.6%, -59.2 +/- 36.6%, and
32.4 +/- 33.5%, respectively. In vitiligo, at 24, 48, and 72 months after MKTP,
53%, 64%, and 53% of ABLs, respectively, maintained >75% repigmentation. Skin
phototype, age, and anatomic location of ABLs had no significant effect on the
outcome of treatment. LIMITATIONS: Limitations of the study include the
retrospective design with uncontrolled, postoperative adjuvant treatments and
inconsistent compliance to scheduled follow-up evaluations. CONCLUSIONS: MKTP
provides satisfactory long-term repigmentation in the majority of appropriately
selected patients with leukoderma. MKTP can maintain repigmentation for at least
72 months.
PMID- 28502378
TI - Long-term treatment of cutaneous manifestations of tuberous sclerosis complex
with topical 1% sirolimus cream: A prospective study of 25 patients.
AB - BACKGROUND: Data on long-term topical sirolimus treatment of the cutaneous
manifestations of tuberous sclerosis complex are rare. OBJECTIVE: To evaluate the
long-term benefit and tolerance of topical 1% sirolimus in tuberous sclerosis
complex. METHODS: In this 18-month prospective single-center study, 1% sirolimus
cream was applied daily to facial angiofibromas (FAs), fibrous cephalic plaques
(FCPs), shagreen patches, hypomelanotic macules, and ungual fibromas. After
complete clearance (CC) of FAs, we evaluated a maintenance protocol of 3
applications weekly. RESULTS: Twenty-five patients were enrolled. Fifty percent
obtained CC of FAs within 9 months. Of 7 patients with CC (58%) who were
following the maintenance protocol, 6 relapsed within 7 months and 1 was still
responding at 1 year. Of 16 patients with FCPs, 7 (44%) remained stable at 12
months and 9 (56%) improved after 3 to 9 months of treatment. Only 1 of 5
patients treated for shagreen patches showed improvement at 12 months. Treatment
was well tolerated with no serious adverse events. LIMITATIONS: The small number
of patients was a limitation. CONCLUSIONS: Topical 1% sirolimus applied daily
produced positive responses in treatment of FAs, FCPs, and facial hypomelanotic
macules and was well tolerated. A 3-times-weekly maintenance protocol did not
prevent FA relapses.
PMID- 28502380
TI - Author's reply to 'Letter to the Editor: Use of Almelo Hip Fracture Score to
predict early mortality following hip fracture surgery'.
PMID- 28502379
TI - External validation of the clinical indications of computed tomography (CT) of
the head in patients with low-energy geriatric hip fractures.
AB - INTRODUCTION: On evaluation of the clinical indications of computed tomography
(CT) scan of head in the patients with low-energy geriatric hip fractures, Maniar
et al. identified physical evidence of head injury, new onset confusion, and
Glasgow Coma Scale (GCS)<15 as predictive risk factors for acute findings on CT
scan. The goal of the present study was to validate these three criteria as
predictive risk factors for a larger population in a wider geographical
distribution. PATIENTS AND METHODS: Patients >=65 years of age with low-energy
hip fractures from 6 trauma centers in a wide geographical distribution in the
United States were included in this study. In addition to the relevant patient
demographic findings, the above mentioned three criteria and acute findings on
head CT scan were gathered as categorical variables. RESULTS: In total 799
patients from 6 centers were included in the study. There were 67 patients (8.3%)
with positive acute findings on head CT scan. All of these patients (100%) had at
least one criteria positive. There were 732 patients who had negative acute
findings on head CT scan with 376 patients (51%) having at least one criteria
positive and 356 patients (49%) having no criteria positive. Sensitivity of 100%
and negative predictive value of 100% was observed to predict negative acute
findings on head CT scan when all the three criteria were negative. CONCLUSION:
With the observed 100% sensitivity and 100% negative predictive value, physical
evidence of acute head injury, acute retrograde amnesia, and GCS<15 can be
recommended as a clinical decision guide for the selective use of head CT scans
in geriatric patients with low energy hip fractures. All the patients with
positive acute head CT findings can be predicted in the presence of at least one
positive criterion. In addition, if these criteria are used as a pre-requisite to
order the head CT, around 50% of the unnecessary head CT scans can be avoided.
PMID- 28502381
TI - Linking lysosomal acid lipase insufficiency to the development of cryptogenic
cirrhosis.
PMID- 28502382
TI - Stochastic contraction based online estimation of second order wiener system.
AB - Wiener system is a block oriented model, having a linear time-invariant dynamic
system followed by a memory-less nonlinearity. To design a stochastic estimator
for online estimation of Wiener system of second order, this paper utilizes
differential mean value theorem and the results of stochastic contraction theory.
The asymptotic convergence of proposed estimator is derived by using contraction
theory related to semi-contracting systems. The boundedness and convergence of
the parameter and state estimates have been shown analytically. The introduced
method has potentials to estimate accurately states and parameters of Wiener
model simultaneously from the noisy output of the system and unknown structure of
nonlinearity. Numerical simulation of the stochastic estimator is presented to
justify the claim by considering the two examples of the real world system with
an additive measurement noise.
PMID- 28502383
TI - Rolling bearing fault diagnosis using adaptive deep belief network with dual-tree
complex wavelet packet.
AB - Automatic and accurate identification of rolling bearing fault categories,
especially for the fault severities and compound faults, is a challenge in
rotating machinery fault diagnosis. For this purpose, a novel method called
adaptive deep belief network (DBN) with dual-tree complex wavelet packet (DTCWPT)
is developed in this paper. DTCWPT is used to preprocess the vibration signals to
refine the fault characteristics information, and an original feature set is
designed from each frequency-band signal of DTCWPT. An adaptive DBN is
constructed to improve the convergence rate and identification accuracy with
multiple stacked adaptive restricted Boltzmann machines (RBMs). The proposed
method is applied to the fault diagnosis of rolling bearings. The results confirm
that the proposed method is more effective than the existing methods.
PMID- 28502384
TI - Sports science needs more interdisciplinary, constraints-led research programmes:
The case of water safety in New Zealand.
AB - In the lead article of this special issue, Paul Glazier proposes that Newell's
constraints model has the potential to contribute to a grand unified theory of
sports performance in that it can help to integrate the disciplinary silos that
have typically operated in isolation in sports and exercise science. With a few
caveats discussed in this commentary, we agree with Glazier's proposal. However,
his ideas suggest that there is a need to demonstrate explicitly how such an
integration might occur within applied scientific research. To help fill this
perceived 'gap' and thereby illustrate the value of adopting a constraints-led
approach, we offer an example of our own interdisciplinary research programme. We
believe our research on water safety is ideally suited to this task due to the
diverse range of interacting constraints present and as such provides a tangible
example of how this approach can unify different disciplinary perspectives
examining an important aspect of sport performance.
PMID- 28502386
TI - ?
PMID- 28502385
TI - The effects of blood glucose regulation on tear function tests in diabetic
patients.
AB - PURPOSE: To investigate whether blood glucose regulation in patients with
diabetes mellitus (DM) has an influence on the ocular surface disease index
(OSDI) score and tear function tests such as tear film osmolarity (TFO), tear
break-up time (TBUT) and Schirmer tests. METHODS: Fifty diabetic patients with a
fasting blood glucose (FBG) level greater than 200mg/dL and HbA1c level greater
than 10% were recruited for this prospective study. All of the patients underwent
a detailed ophthalmic examination including OSDI questionnaire, TFO test, TBUT
test and Schirmer test initially. All tests were repeated after obtaining
regulation of patients' blood sugar (approximately 6 weeks later). RESULTS: The
mean age of the diabetic patients in the study was 54.96+/-12.48 years.
Initially, the mean FBG, postprandial blood glucose (PBG) and HbA1c levels were
301.40+/-79.11mg/dL, 431.06+/-74.47mg/dL and 12.31+/-1.67%, respectively. After
blood glucose regulation; the levels of all parameters (153.78+/-59.32mg/dL,
252.32+/-88.34mg/dL and 9.67+/-1.60%, respectively) statistically significantly
decreased (P<0.001). The mean levels of OSDI score, TFO measurement, TBUT test
and Schirmer test were 28.38+/-16.46 points, 349.66+/-13.09 mOsm/L, 6.44+/-1.91s
and 8.66+/-3.57mm initially, and 17.82+/-11.70 points, 314.14+/-12.80 mOsm/L,
6.62+/-2.03s and 9.02+/-3.68mm after blood glucose regulation, respectively.
Although the improvements in TBUT and Schirmer test values were not statistically
significant (P>0.05), statistically significant reduction was obtained in OSDI
scores and TFO levels (P<0.001, for each). CONCLUSION: DM, which is a
hyperosmolar disorder, appears to cause elevation in OSDI score and increase in
TFO level, especially if blood glucose is poorly regulated.
PMID- 28502387
TI - Anterolateral Ligament Reconstruction Techniques, Biomechanics, and Clinical
Outcomes: A Systematic Review.
AB - PURPOSE: To perform a systematic review of the described anterolateral ligament
(ALL) reconstruction techniques, biomechanical performance, and clinical outcomes
of ALL reconstruction in the setting of concurrent anterior cruciate ligament
(ACL) reconstruction. METHODS: A systematic review was performed according to
PRISMA guidelines using the Cochrane Database of Systematic Reviews, the Cochrane
Central Register of Controlled Trials, PubMed, MEDLINE, and Embase, from 1980 to
present. Inclusion criteria were as follows: ALL reconstruction techniques, ALL
reconstruction biomechanical studies, ALL surgical outcomes, English language,
human studies with at least 2 years of follow-up, and cadaveric studies.
Exclusion criteria were lateral extra-articular tenodesis, ALL anatomic studies,
ALL radiographic studies, animal studies, clinical studies with <2 years of
follow-up, editorial articles, and surveys. RESULTS: The systematic review
identified 12 articles that met the inclusion criteria: 6 techniques, 5
biomechanical studies, and 1 outcome study were available. Five studies described
ALL reconstruction in the setting of ACL reconstruction, whereas 1 study
described isolated ALL reconstruction. Femoral tunnel location was most commonly
placed posterior and proximal to the lateral epicondyle, whereas 2 studies
reported a distal tunnel location. There was little variability in tibial tunnel
location. The most common ALL reconstruction graft used was the gracilis tendon.
Review of the biomechanical studies revealed internal rotation overconstraint
with the posterior/proximal femoral tunnel position but not anterior/distal,
although fixation angle and graft tension were inconsistent. Only 1 clinical
study with 2 years' follow-up was available and reported improvement in the
majority of cases. Complications occurred in 15 patients, including a residual
pivot shift in 8% of patients at 2 years after a combined ACL and ALL
reconstruction. CONCLUSIONS: There is inconsistency in the selection of ALL graft
femoral attachment location as well as in the biomechanical performance of ALL
reconstruction techniques. LEVEL OF EVIDENCE: Level IV, systematic review of
Level IV studies.
PMID- 28502388
TI - The Grapefruit: An Alternative Arthroscopic Tool Skill Platform.
AB - PURPOSE: To establish the construct validity of an arthroscopic training model
that teaches arthroscopic tool skills including triangulation, grasping,
precision biting, implant delivery and ambidexterity and uses a whole grapefruit
for its training platform. METHODS: For the grapefruit training model (GTM), an
arthroscope and arthroscopic instruments were introduced through portals cut in
the grapefruit skin of a whole prepared grapefruit. After institutional review
board approval, participants performed a set of tasks inside the grapefruit.
Performance for each component was assessed by recording errors, achievement of
criteria, and time to completion. A total of 19 medical students, orthopaedic
surgery residents, and fellowship-trained orthopaedic surgeons were included in
the analysis and were divided into 3 groups based on arthroscopic experience. One
way analysis of variance (ANOVA) and the post hoc Tukey test were used for
statistical analysis. RESULTS: One-way ANOVA showed significant differences in
both time to completion and errors between groups, F(2, 16) = 16.10, P < .001;
F(2, 16) = 17.43, P < .001. Group A had a longer time to completion and more
errors than group B (P = .025, P = .019), and group B had a longer time to
completion and more errors than group C (P = .023, P = .018). CONCLUSIONS: The
GTM is an easily assembled and an alternative arthroscopic training model that
bridges the gap between box trainers, cadavers, and virtual reality simulators.
Our findings suggest construct validity when evaluating its use for teaching the
basic arthroscopic tool skills. As such, it is a useful addition to the
arthroscopic training toolbox. CLINICAL RELEVANCE: There is a need for validated
low-cost arthroscopic training models that are easily accessible.
PMID- 28502389
TI - A Glitch in the Matrix: Aberrant Extracellular Matrix Proteolysis Contributes to
Alcohol Seeking.
PMID- 28502390
TI - Tipping the Scales Toward Addiction.
PMID- 28502392
TI - Retraction.
PMID- 28502391
TI - Bed Nucleus of the Stria Terminalis-Derived Corticotropin-Releasing Factor
Controls Binge Alcohol Drinking Via Interacting With Corticotropin-Releasing
Factor Receptors 1 and 2 in the Ventral Tegmental Area.
PMID- 28502393
TI - As Hopes Have Flown Before: Toward the Rational Design of Treatments for Alcohol
Use Disorder.
PMID- 28502394
TI - Similitude in Methamphetamine-Induced Neuroadaptations Across Susceptibility and
Chronic Drug Exposure Paradigms.
PMID- 28502395
TI - Multicenter evaluation of the RAPIDEC(r) CARBA NP test for rapid screening of
carbapenemase-producing Enterobacteriaceae and Gram-negative nonfermenters from
clinical specimens.
AB - The rapid diagnosis of carbapenemase-producing (CP) bacteria is essential for the
management of therapy and infection control. In this study, RAPIDEC(r) CARBA NP
(RCNP) was evaluated for the rapid screening of CP Enterobacteriaceae,
Acinetobacter baumannii complex, and Pseudomonas aeruginosa from clinical
specimens collected at five Italian hospitals. Firstly, each site tested 20 well
characterized strains in a blinded fashion. Secondly, each center prospectively
tested 25 isolates from blood cultures processed with a rapid workflow (6h after
subculture) and 25 isolates from other specimens processed after an overnight
culture. The presence of carbapenemases was confirmed by multiplex real-timePCRs
targeting carbapenemase genes. RCNP presented an overall sensitivity,
specificity, positive predictive value, and negative predictive value of 70%,
94%, 82%, and 89%, respectively, with a higher performance in detection of CP
Enterobacteriaceae and a poorer performance in detection of CP A. baumannii
complex. With isolates from blood cultures, RCNP could significantly reduce the
time required for identification of CP Enterobacteriaceae (less than 9h since the
positivization of blood cultures).
PMID- 28502396
TI - Comparative evaluation of 2 rapid immunochromatographic assays for Orientia
tsutsugamushi in northeastern Thailand.
PMID- 28502397
TI - Performance of the check-points check-MDR CT103XL assay utilizing the CDC/FDA
antimicrobial resistance isolate bank.
AB - The Check-MDR CT103XL beta-lactamase assay was validated for use in the clinical
microbiology laboratory using two CDC-FDA Antimicrobial Resistant Isolate Bank
panels (133 gram-negative bacilli known beta-lactamase genes). The CT103XL
detected most reported resistance genes (123 of 136 genes) and additionally
identified several resistance genes not reported by the CDC. Discrepant results
were confirmed via whole genome sequencing.
PMID- 28502398
TI - Correlations between individual susceptibility to visually induced motion
sickness and decaying time constant of after-nystagmus.
AB - This study examines the correlations between optokinetic after-nystagmus (OKAN)
parameters and individual susceptibility to visually induced motion sickness
(VIMS). Twenty-seven participants were exposed to vertical black-and-white
stripes drifting along the yaw axis at 60 degrees per second for 30 min to
collect individual VIMS data (Phase 1). Two weeks after the exposure, OKANs were
measured (Phase 2). 19 out of 27 participants (i.e., 70%) exhibited consistent
OKAN patterns. Significant correlations between the time constants of OKAN and
levels of VIMS experienced by the same viewers were found. Four months later,
these 27 participants were invited back for a second OKAN measurement (Phase 3).
Twenty-one participants came back. Their two OKAN measurements were significantly
correlated (r = 0.69, p = 0.001). Rated levels of VIMS in phase 1 significantly
correlated with the time constant of OKAN in both Phase 2 (r = 0.51, p = 0.044)
and Phase 3 (r = 0.74, p = 0.006). The implications of the correlation results
are discussed.
PMID- 28502399
TI - User roles and contributions during the new product development process in
collaborative innovation communities.
AB - Collaborative innovation (co-innovation) community emerges as a new product
design platform where companies involve users in the new product development
(NPD) process. Large numbers of users participate and contribute to the process
voluntarily. This exploratory study investigates the heterogeneous roles of users
based on a global co-innovation project in online community. Content analysis,
social network analysis and cluster method are employed to measure user
behaviors, distinguish user roles, and analyze user contributions. The study
identifies six user roles that emerge during the NPD process in co-innovation
community: project leader, active designer, generalist, communicator, passive
designer, and observer. The six user roles differ in their contribution forms and
quality. This paper contributes to research on co-innovation in online
communities, including design team structure, user roles and their contribution
to design task and solution, as well as user value along the process. In
addition, the study provides practices guidance on implementing project,
attracting users, and designing platform for co-innovation community
practitioners.
PMID- 28502400
TI - Bags, batteries and boxes: A qualitative interview study to understand how
syringe drivers are adapted and used by healthcare staff.
AB - Syringe drivers are medical devices that are critical for end of life care. They
deliver continuous medication over extended periods of time. Their design
contributes to the quality of experience for both patients and healthcare
professionals. Little research has been published about the factors that
influence the usability of this type of equipment for frontline users (i.e. those
in direct contact with patients) and how equipment gets introduced. Understanding
how syringe drivers are used in practice can help improve the design of
equipment. 27 semi-structured interviews were conducted across acute hospitals,
community hospitals and hospices (4 organisations in total). All participating
organisations used the same type of syringe driver. It was found that frontline
staff needed to adapt this equipment to fit the circumstances of use. The
analysis provided examples of this happening for aspects relating to the
appearance of the device (bags), accessories (batteries) and security (the
lockable box).
PMID- 28502401
TI - Effect of local magnetic field disturbances on inertial measurement units
accuracy.
AB - Inertial measurement units (IMUs), a practical motion analysis technology for
field acquisition, have magnetometers to improve segment orientation estimation.
However, sensitivity to magnetic disturbances can affect their accuracy. The
objective of this study was to determine the joint angles accuracy of IMUs under
different timing of magnetic disturbances of various durations and to evaluate a
few correction methods. Kinematics from 12 individuals were obtained
simultaneously with an Xsens system where an Optotrak cluster acting as the
reference system was affixed to each IMU. A handling task was executed under
normal laboratory conditions and imposed magnetic disturbances. Joint angle RMSE
was used to conduct a three-way repeated measures analysis of variance in order
to contrast the following disturbance factors: duration (0, 30, 60, 120 and 240
s), timing (during the disturbance, directly after it and a 30-second delay after
it) and axis (X, Y and Z). The highest joint angle RMSE was observed on rotations
about the Y longitudinal axis and during the longer disturbances. It stayed high
directly after a disturbance, but returned close to baseline after a 30-second
delay. When magnetic disturbances are experienced, waiting 30 s in a normal
condition is recommended as a way to restore the IMUs' initial accuracy. The
correction methods performed modestly or poorly in the reduction of joint angle
RMSE.
PMID- 28502402
TI - Decisionmaking in practice: The dynamics of muddling through.
AB - An alternative to conventional models that treat decisions as open-loop
independent choices is presented. The alterative model is based on observations
of work situations such as healthcare, where decisionmaking is more typically a
closed-loop, dynamic, problem-solving process. The article suggests five
important distinctions between the processes assumed by conventional models and
the reality of decisionmaking in practice. It is suggested that the logic of
abduction in the form of an adaptive, muddling through process is more consistent
with the realities of practice in domains such as healthcare. The practical
implication is that the design goal should not be to improve consistency with
normative models of rationality, but to tune the representations guiding the
muddling process to increase functional perspicacity.
PMID- 28502403
TI - The role of driver age in performance and attention allocation effects of roadway
sign count, format and familiarity.
AB - White-on-blue logo signs are used to inform drivers of food, gas, lodging, and
attraction businesses at highway interchanges. In this study, 60 drivers were
asked to look for food and attraction targets on logo signs while driving in a
realistic freeway simulation. The objective of the study was to quantify effects
of the number of sign panels (six vs. nine), logo familiarity (familiar vs.
unfamiliar), logo format (text vs. pictorial), and driver age (young, middle, and
elderly) on performance, attention allocation and target identification accuracy.
Results revealed elderly drivers to exhibit worse performance in comparison to
middle-age and young groups even though they adopted a more conservative driving
strategy. There was no significant effect of the number of panels, logo
familiarity, and logo format on driver performance or attention allocation. In
target identification, drivers were more accurate with familiar or text-based
panels appearing in six-panel signs.
PMID- 28502404
TI - Application of classification principles to improve the reliability of incident
classification systems: A test case using HFACS-ADF.
AB - Accident classification systems are important tools for safety management.
Unfortunately, many of the tools available have demonstrated poor reliability of
coding, making their validity and usefulness questionable. This paper
demonstrates the application of four strategies to improve the reliability of
accident and incident classification systems. The strategies include creating a
domain-specific system with limitations on system size and careful selection of
codes, specifically the reduction of abstract concepts and bias-causing
terminology. Using HFACS-ADF as a test case, the system was adapted using the
strategies and validated using comprehension and comprehensiveness testing. The
new system was then assessed for reliability. The reliability of the system
increased by at least 20% at all levels of the classification system following
the changes made. The results provide evidence that the application of
theoretically and empirically-derived classification principles are effective for
improving the reliability of accident and incident classification systems in high
hazard industries.
PMID- 28502405
TI - A practical guidance for assessments of sedentary behavior at work: A PEROSH
initiative.
AB - Sedentary behavior is defined as sitting or lying with low energy expenditure.
Humans in industrialized societies spend an increasing amount of time in
sedentary behaviors every day. This has been associated with detrimental health
outcomes. Despite a growing interest in the health effects of sedentary behavior
at work, associations remain unclear, plausibly due to poor and diverse methods
for assessing sedentary behavior. Thus, good practice guidance for researchers
and practitioners on how to assess occupational sedentary behavior are needed.
The aim of this paper is to provide a practical guidance for practitioners and
researchers on how to assess occupational sedentary behavior. Ambulatory systems
for use in field applications (wearables) are a promising approach for sedentary
behavior assessment. Many different small-size consumer wearables, with long
battery life and high data storage capacity are commercially available today.
However, no stand-alone commercial system is able to assess sedentary behavior in
accordance with its definition. The present paper offers decision support for
practitioners and researchers in selecting wearables and data collection
strategies for their purpose of study on sedentary behavior. Valid and reliable
assessment of occupational sedentary behavior is currently not easy. Several
aspects need to be considered in the decision process on how to assess sedentary
behavior. There is a need for development of a cheap and easily useable wearable
for assessment of occupational sedentary behavior by researchers and
practitioners.
PMID- 28502406
TI - Steering the conversation: A linguistic exploration of natural language
interactions with a digital assistant during simulated driving.
AB - Given the proliferation of 'intelligent' and 'socially-aware' digital assistants
embodying everyday mobile technology - and the undeniable logic that utilising
voice-activated controls and interfaces in cars reduces the visual and manual
distraction of interacting with in-vehicle devices - it appears inevitable that
next generation vehicles will be embodied by digital assistants and utilise
spoken language as a method of interaction. From a design perspective, defining
the language and interaction style that a digital driving assistant should adopt
is contingent on the role that they play within the social fabric and context in
which they are situated. We therefore conducted a qualitative, Wizard-of-Oz study
to explore how drivers might interact linguistically with a natural language
digital driving assistant. Twenty-five participants drove for 10 min in a medium
fidelity driving simulator while interacting with a state-of-the-art, high
functioning, conversational digital driving assistant. All exchanges were
transcribed and analysed using recognised linguistic techniques, such as
discourse and conversation analysis, normally reserved for interpersonal
investigation. Language usage patterns demonstrate that interactions with the
digital assistant were fundamentally social in nature, with participants
affording the assistant equal social status and high-level cognitive processing
capability. For example, participants were polite, actively controlled turn
taking during the conversation, and used back-channelling, fillers and
hesitation, as they might in human communication. Furthermore, participants
expected the digital assistant to understand and process complex requests
mitigated with hedging words and expressions, and peppered with vague language
and deictic references requiring shared contextual information and mutual
understanding. Findings are presented in six themes which emerged during the
analysis - formulating responses; turn-taking; back-channelling, fillers and
hesitation; vague language; mitigating requests and politeness and praise. The
results can be used to inform the design of future in-vehicle natural language
systems, in particular to help manage the tension between designing for an
engaging dialogue (important for technology acceptance) and designing for an
effective dialogue (important to minimise distraction in a driving context).
PMID- 28502408
TI - Combined effect of low back muscle fatigue and passive tissue elongation on the
flexion-relaxation response.
AB - Previous literature has documented the alterations in the flexion-relaxation
response of the lumbar extensor musculature to passive tissue elongation (PTE)
and muscle fatigue (MF). There is no study, however, that has explored this
response as a function of the combined effect of both PTE and MF, which is often
seen in occupational settings. Twelve participants performed three experimental
protocols on three different days to achieve (1) PTE, (2) MF and (3) PTE&MF
(combined). Trunk kinematics and muscle activities were monitored to assess the
effects of these protocols on the peak lumbar flexion angle and the lumbar angle
of the flexion-relaxation of the trunk extensor muscles. Results showed responses
to the uni-dimensional stresses (PTE and MF) consistent with those seen in the
previous literature, while the combined protocol elicited responses that more
closely matched the PTE protocol.
PMID- 28502407
TI - I spy with my little eye: Analysis of airline pilots' gaze patterns in a manual
instrument flight scenario.
AB - The aim of this study was to analyze pilots' visual scanning in a manual approach
and landing scenario. Manual flying skills suffer from increasing use of
automation. In addition, predominantly long-haul pilots with only a few
opportunities to practice these skills experience this decline. Airline pilots
representing different levels of practice (short-haul vs. long-haul) had to
perform a manual raw data precision approach while their visual scanning was
recorded by an eye-tracking device. The analysis of gaze patterns, which are
based on predominant saccades, revealed one main group of saccades among long
haul pilots. In contrast, short-haul pilots showed more balanced scanning using
two different groups of saccades. Short-haul pilots generally demonstrated better
manual flight performance and within this group, one type of scan pattern was
found to facilitate the manual landing task more. Long-haul pilots tend to
utilize visual scanning behaviors that are inappropriate for the manual ILS
landing task. This lack of skills needs to be addressed by providing specific
training and more practice.
PMID- 28502409
TI - Field evaluation of a wearable multimodal soldier navigation system.
AB - Challenging environments pose difficulties for terrain navigation, and therefore
wearable and multimodal navigation systems have been proposed to overcome these
difficulties. Few such navigation systems, however, have been evaluated in field
conditions. We evaluated how a multimodal system can aid in navigating in a
forest in the context of a military exercise. The system included a head-mounted
display, headphones, and a tactile vibrating vest. Visual, auditory, and tactile
modalities were tested and evaluated using unimodal, bimodal, and trimodal
conditions. Questionnaires, interviews and observations were used to evaluate the
advantages and disadvantages of each modality and their multimodal use. The
guidance was considered easy to interpret and helpful in navigation. Simplicity
of the displayed information was required, which was partially conflicting with
the request for having both distance and directional information available.
PMID- 28502410
TI - Performance awareness: Predicting cognitive performance during simulated
shiftwork using chronobiological measures.
AB - Physiological tracers of circadian rhythms and a performance awareness index were
examined as predictors of cognitive performance during two sleep deprivation
conditions common to occupational shiftwork. Study 1: Thirty-three sleep-deprived
participants completed a simulated nightshift. Study 2: Thirty-two partially
sleep-deprived participants completed a simulated dayshift. A standardized logic
test was used to measure cognitive performance. Body temperature and heart rate
were measured as chronobiological indices of endogenous circadian rhythms.
Performance awareness was calculated as a correlation between actual and
perceived performance. These studies demonstrated a parallelism between
performance awareness and the circadian rhythm. Chronobiological changes were
predictive of performance awareness during the simulated nightshift but not
dayshift. Only oral temperature was a significant independent predictor. Oral
temperature predicted an individual's awareness of their own performance better
than their own subjective awareness. These findings suggest that using circadian
rhythms in applied ergonomics may reduce occupational risk due to low performance
awareness.
PMID- 28502411
TI - Abdominal bracing during lifting alters trunk muscle activity and body
kinematics.
AB - We assessed whether participants are able to perform abdominal bracing during
lifting, and described its effects on trunk muscle activity and body kinematics.
Fourteen participants performed 10 lifts (symmetrical lifting of a 15 kg load
from floor level), 5 with abdominal bracing and 5 without. Activity of the lumbar
multifidus (LM) and internal oblique (IO) muscles, and trunk and lower body
kinematics were obtained. During non-bracing lifting, IO activity did not
increase beyond rested standing levels (with average muscle activity ranging
between 8.2 and 9.1% maximum voluntary contraction; %MVC), while LM activity did
(range: 8.5-21.0 %MVC). During bracing lifting, muscle activity was higher
compared to non-bracing in IO and LM at the start of the lift (with average
between condition differences up to 10.9 %MVC). Upper leg, pelvis and lumbar
spine angles were smaller, but thorax flexion angles were larger while lifting
with bracing compared to without (with average between condition differences
ranging from 0.7 degrees to 4.3 degrees ). Although participants do not
typically brace their abdominal muscles while lifting, they can be trained to do
so. There appears to be no clear advantage of abdominal bracing during lifting,
leaving its value for low-back pain prevention unclear.
PMID- 28502412
TI - Computer-based estimation of the hip joint reaction force and hip flexion angle
in three different sitting configurations.
AB - Sitting is part of our daily work and leisure activities and can be performed in
different configurations. To date, the impact of different sitting configurations
on hip joint loading has not been studied. We therefore evaluated the hip joint
reaction force (HJRF) and hip flexion angle in a virtual representative male
Caucasian population by means of musculoskeletal modelling of three distinct
sitting configurations: a simple chair, a car seat and a kneeling chair
configuration. The observed median HJRF in relation to body weight and hip
flexion angle, respectively, was 22.3% body weight (%BW) and 63 degrees for the
simple chair, 22.5%BW and 79 degrees for the car seat and 8.7%BW and 50 degrees
for the kneeling chair. Even though the absolute values of HJRF are low compared
to the forces generated during dynamic activities, a relative reduction of over
50% in HJRF was observed in the kneeling chair configuration. Second, the hip
flexion angles were both in the kneeling chair (-29 degrees ) and simple chair
configuration (-16 degrees ) lower compared to the car seat and, as such, did not
reach the threshold value for femoroacetabular conflict. In conclusion, the
kneeling chair appears to hold the greatest potential as an ergonomic sitting
configuration for the hip joint.
PMID- 28502413
TI - Understanding the determinants of health-related quality of life in rheumatoid
arthritis-associated interstitial lung disease.
AB - RATIONALE: Health-related quality of life (HRQL) is impaired among patients with
interstitial lung disease (ILD). Little is understood about HRQL in specific
subtypes of ILD. OBJECTIVES: The aim of this study was to characterize and
identify clinical determinants of HRQL among patients with rheumatoid arthritis
associated interstitial lung disease (RA-ILD) and compare them to patients with
idiopathic pulmonary fibrosis (IPF). METHODS: We identified patients with a
diagnosis of RA-ILD and IPF from an ongoing longitudinal cohort of ILD patients.
HRQL was measured at their baseline visit using the Short Form Health Survey (SF
36), versions 1 and 2. Regression models were used to characterize and understand
the relationship between selected baseline clinical covariates, the physical
component score (PCS) and mental component score (MCS) of the SF-36. MEASUREMENTS
AND MAIN RESULTS: RA-ILD patients (n = 50) were more likely to be younger and
female compared to IPF patients (n = 50). After controlling for age and pulmonary
function, RA-ILD patients had a lower HRQL compared to IPF patients, as measured
by the PCS (P = 0.03), with significant differences in two of four PCS domains -
bodily pain (P < 0.01) and general health (P = 0.01). Clinical covariates most
strongly associated with a lower PCS in RA-ILD patients compared to IPF patients
were the presence of joint pain or stiffness and dyspnea severity (P < 0.01).
Mental and emotional health, as measured by the MCS, was similar between RA-ILD
and IPF patients. CONCLUSION: The physical components of HRQL appear worse in RA
ILD patients compared to IPF patients as measured by the PCS of the SF-36.
Differences in the PCS of the SF-36 can be explained in part by dyspnea severity
and joint symptoms among patients with RA-ILD.
PMID- 28502415
TI - Effects of acute psychological stress induced in laboratory on physiological
responses in asthma populations: A systematic review.
AB - BACKGROUND: Psychological stress has long been suspected to have a deleterious
effect on asthma, with acute psychological stress being associated with
physiological responses in asthma patients. OBJECTIVES: The purpose of this
systematic review was to provide a narrative synthesis of the impact of acute
laboratory psychological stress on physiological responses among asthma patients.
METHODS: An extensive search was conducted by two independent authors using
Pubmed, PsycINFO, PsyArticles and the Cochrane Library electronic databases (up
to September 2016). English and French articles which assessed physiological
responses during or post-stress and compare them to baseline or pre-stress values
were included. RESULTS: Thirty-two studies met the inclusion criteria. Studies
indicated that exposure to active stressors (e.g., arithmetic tasks) was
associated with an increase in sympathetic nervous system (SNS) responses,
cortisol, and inflammatory responses, but had little effect on the caliber of the
bronchi. Exposure to passive stressors (e.g., watching stressful movies or
pictures) was also associated with an increase in SNS responses and with mild
bronchoconstriction. However, a paucity of data for passive stressors limited
conclusions on other measures. CONCLUSIONS: In patients with asthma, both active
and passive stressors seem to be associated with an increased activation of the
SNS. Passive stressors seem to have a more immediate, deleterious impact on the
airways than active stressors, but the latter may be associated with delayed
inflammatory driven an asthma exacerbation. Further studies are needed to
understand the impact of acute stressors on the physiological mechanisms
associated with asthma, particularly HPA and immune markers. Systematic review
registration number: CRD42015026431.
PMID- 28502414
TI - Acute bronchodilator responses to beta2-agonist and anticholinergic agent in
COPD: Their different associations with exacerbation.
AB - BACKGROUND: Acute bronchodilator response (BDR) is a potential phenotypic
characteristic of COPD. However, the clinical factors associated with BDR in
patients with COPD remain unclear, particularly for BDR to anticholinergic
agents. OBJECTIVES: We aimed to clarify the clinical factors associated with BDR
to beta2-agonist and/or anticholinergic agent, considering time-associated
variations of BDR. We also evaluated the association between BDR and clinical
course of COPD. METHODS: We analyzed 152 subjects who participated in the
Hokkaido COPD cohort study. We repeatedly measured BDR to salbutamol (400 MUg) or
oxitropium (400 MUg) three times for each every 6 months alternately over 3
years. Reversibility was defined by >= 12% and >=200 mL increase in FEV1 over
baseline. All subjects were classified into three groups based on the BDR
stability; consistently reversible, consistently irreversible, and inconsistent.
We compared baseline clinical characteristics and the 5-year clinical course of
COPD among the three groups. RESULTS: For either agent, the mean blood eosinophil
count was significantly higher in those with consistently reversible than those
with consistently irreversible (p < 0.05). The subjects with consistently
reversible to oxitropium (p < 0.05), but not to salbutamol (p = 0.56), showed
increased risk of exacerbation compared with the other two groups. CONCLUSION: We
identified the distinct clinical characteristics of COPD associated with acute
BDR status. Increased cholinergic airway tone, which is reflected in the higher
BDR only to anticholinergic agent, but not to beta2-agonist, may be associated
with exacerbation in COPD.
PMID- 28502416
TI - The heterogeneity of systemic inflammation in bronchiectasis.
AB - BACKGROUND: Systemic inflammation in bronchiectasis is poorly studied in relation
to aetiology and severity. We hypothesized that molecular patterns of
inflammation may define particular aetiology and severity groups in
bronchiectasis. METHOD: We assayed blood concentrations of 31 proteins from 90
bronchiectasis patients (derivation cohort) and conducted PCA to examine
relationships between these markers, disease aetiology and severity. Key results
were validated in two separate cohorts of 97 and 79 patients from other centres.
RESULTS: There was significant heterogeneity in protein concentrations across the
derivation population. Increasing severity of bronchiectasis (BSI) was associated
with increasing fibrinogen (rho = 0.34, p = 0.001 -validated in a second cohort),
and higher fibrinogen was associated with worse lung function, Pseudomonas
colonisation and impaired health-status. There were generally similar patterns of
inflammation in patients with idiopathic and post-infectious disease. However,
patients with primary immunodeficiency had exaggerated IL-17 responses, validated
in a second cohort (n = 79, immunodeficient 12.82 pg/ml versus idiopathic/post
infectious 4.95 pg/ml, p = 0.001), and thus IL-17 discriminated primary
immunodeficiency from other aetiologies (AUC 0.769 (95%CI 0.661-0.877)).
CONCLUSION: Bronchiectasis is associated with heterogeneity of systemic
inflammatory proteins not adequately explained by differences in disease
aetiology or severity. More severe disease is associated with enhanced acute
phase responses. Plasma fibrinogen was associated with bronchiectasis severity in
two cohorts, Pseudomonas colonisation and health status, and offers potential as
a useful biomarker.
PMID- 28502417
TI - Analysis of bronchial biopsies in chronic cough.
AB - BACKGROUND: Chronic cough is commonly associated with asthma, gastro-oesophageal
reflux disease and postnasal drip, but in a significant proportion, no associated
cause can be found. We determined whether examination of bronchial biopsies would
be useful in determining the cause associated with chronic cough. METHODS: 100
consecutive patients referred to a specialist cough clinic underwent a systematic
assessment including a fiberoptic bronchoscopy for bronchial biopsies. RESULTS:
In 38 patients, treatment of associated causes led to amelioration of cough
('explained') and in 62, there was no association or improvement ('idiopathic').
The latter group had a longer duration of cough, a lower FeNO levels and a more
sensitive capsaicin cough response, with an increase in basement membrane
thickness with no differences in goblet cell hyperplasia and seromucinous
hyperplasia, and in lymphocyte, neutrophil and eosinophil counts. The duration of
cough was inversely correlated with the degree of neutrophil infiltration.
CONCLUSION: We conclude that pathological examination of bronchial biopsies is
unlikely to be useful in the diagnosis of chronic cough in non-smokers.
PMID- 28502418
TI - A multicenter, cross-sectional, observational study of budesonide/formoterol
maintenance and reliever therapy in real-world settings.
AB - BACKGROUND: To assess the level of asthma control achieved with
budesonide/formoterol in Chinese patients with asthma, based on the Global
Initiative for Asthma (GINA) definition and Asthma Control Test (ACT) score.
METHODS: This multicenter, cross-sectional study (NCT01785901) evaluated asthma
control levels in Chinese patients receiving physician-prescribed
budesonide/formoterol treatment. Adults with a diagnosis of asthma >=6 months and
receiving budesonide/formoterol treatment >=3 months before screening were
consecutively enrolled. Data including medical and medication history were
collected using face-to-face questionnaires and physical examinations during a
single visit. RESULTS: A total of 1483 asthma out-patients from 27 medical
centers were enrolled; 217 (14.6%) were treated with budesonide/formoterol using
a fixed-dose strategy and 1266 (85.4%) with the SMART (Symbicort(r) Maintenance
And Reliever Therapy) strategy. According to GINA criteria, asthma was controlled
in 58.6% (95% CI: 56.1%-61.1%) of patients and was either controlled or partly
controlled in 94.1% (95% CI: 92.8%-95.3%) of patients. According to ACT score,
asthma was completely controlled in 22.4% (95% CI: 20.3%-24.6%) of patients and
was either completely or well controlled in 83.3% (95% CI: 81.4%-85.2%) of
patients. Multivariate logistic regression analysis revealed that a >5-year
history of asthma and an age of >50 years were factors associated with lower
levels of asthma control. CONCLUSIONS: This study demonstrated high levels of
asthma control (GINA: controlled and partly controlled and ACT: completely and
well controlled) in Chinese patients with asthma treated with
budesonide/formoterol. Greater age and a longer disease history were associated
with lower levels of asthma control. TRIAL REGISTRATION:
ClinicalTrials.govNCT01785901. Registered February 5, 2013.
PMID- 28502420
TI - Cardiopulmonary exercise testing and second-line pulmonary function tests to
detect obstructive pattern in symptomatic smokers with borderline spirometry.
AB - BACKGROUND: The need for additional research on symptomatic smokers with normal
spirometry has been recently emphasized. Albeit not meeting criteria for Chronic
obstructive pulmonary disease (COPD) diagnosis, symptomatic smokers may
experience activity limitation, evidence of airway disease, and exacerbations.
We, therefore, evaluated whether symptomatic smokers with borderline spirometry
(post-bronchodilator FEV1/FVC ratio between 5th to 20th percentile of predicted
values) have pulmonary function abnormalities at rest and ventilatory constraints
during exercise. METHODS: 48 subjects (aged 60 +/- 8 years, mean +/- SD, 73%
males, 16 healthy, and 17 symptomatic smokers) underwent cardiopulmonary exercise
testing (CPET), body plethysmography, nitrogen single-breath washout test
(N2SBW), lung diffusion for carbon monoxide (DLCO), and forced oscillation
technique (FOT). RESULTS: Compared to healthy subjects, symptomatic smokers
showed: 1) reduced breathing reserve (36 +/- 17 vs. 49 +/- 12%, P = 0.050); 2)
exercise induced dynamic hyperinflation (-0.20 +/- 0.17 vs. -0.03 +/- 0.21 L, P =
0.043); 3) higher residual volume (158 +/- 22 vs. 112 +/- 22%, P < 0.001); 4)
phase 3 slope at N2SBW (4.7 +/- 2.1 vs. 1.4 +/- 0.6%, P < 0.001); 5) no
significant differences in DLCO and FOT results. CONCLUSIONS: In smokers with
borderline spirometry, CPET and second-line pulmonary function tests may detect
obstructive pattern. These subjects should be referred for second line testing,
to obtain a diagnosis, or at least to clarify the mechanisms underlying symptoms.
Whether the natural history of these patients is similar to COPD, and they
deserve a similar therapeutic approach is worth investigating.
PMID- 28502421
TI - Is neoadjuvant chemoradiotherapy always necessary for mid/high local advanced
rectal cancer: A comparative analysis after propensity score matching.
AB - AIM: This study was aimed to compare perioperative and oncological outcomes of
mid/high locally advanced midrectal cancer (LARC) treated with neoadjuvant
chemoradiotherapy (NCRT) vs. surgery alone, and to identify risk factors for
local recurrence in mid/high LARC. METHOD: A total of 471 mid/high LARC patients
treated with surgery alone or NCRT (50.4 Gy in 28 fractions) with concurrent
FOLFOX/XELOX followed by TME in 6-8 weeks from 2008 to 2014 were matched 1:1 by
using propensity score analysis. Perioperative and survival outcome was compared
between groups. Multivariate analyze was performed to identify risk factors for
local recurrence. RESULTS: Two hundred and two patients were matched for the
analysis. Postoperative morbidity was similar between groups. With a mean follow
up of 57 months, the 5-year overall survival (NCRT vs. surgery alone: 80.4% vs.
81.4%; p = 0.978), 5-year local recurrence rates (3.1% vs. 5%; p = 0.467), and 5
year distant metastasis rates (29.5% vs. 23.7%; p = 0.140) were similar between
two groups. Cox regression analysis showed that the circumferential resection
margin (CRM) involvement (OR = 5.205, p = 0.005) was the only risk factor for
local recurrence in mid/high LARC patients. CONCLUSION: In matched cohorts of
mid/high LARC patients, surgery alone provided comparable oncological outcome,
when compared with NCRT. CRM involvement was the only risk factor for local
recurrence in mid/high rectal cancer. NCRT may not be always needed in mid/high
LARC. A threatened CRM could be diagnosed up front and prevented by selecting CRT
for these patients.
PMID- 28502422
TI - Preimplantation genetic diagnosis for monogenic diseases.
AB - Preimplantation genetic diagnosis (PGD) was first reported in 1990. Thereafter,
more and more indications for PGD, including monogenic diseases (MGD) and
translocations, are presently available, and the list of indications of PGD is
expanding from early-onset and serious conditions to late-onset diseases.
Polymerase chain reaction has been used for PGD of MGD, while newer techniques,
including karyomapping and next-generation sequencing, emerge in recent decade.
The limitations of various methods for PGD are discussed in this review.
PMID- 28502419
TI - The performance of the GAP model in patients with rheumatoid arthritis associated
interstitial lung disease.
AB - BACKGROUND: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is
associated with significant morbidity and mortality. Similarities have been
observed between patients with idiopathic pulmonary fibrosis (IPF) and the UIP
(usual interstitial pneumonia) form of RA-ILD. The GAP (gender, age, physiology)
model has been shown to predict mortality in patients with IPF, but its ability
to predict mortality in RA-ILD is not known. METHODS: We identified 309 patients
with RA-ILD at 4 academic centers with ongoing longitudinal cohorts of patients
with ILD. The primary endpoint was mortality. To handle missing data (n = 219
subjects with complete dataset), multiple imputation by iterative chained
equations was used. Using the GAP model as a baseline, we assessed improvements
in mortality risk prediction achieved by incorporating additional variables.
Model discrimination was assessed using the c-index, and calibration was checked
by comparing observed and expected incidence of death. RESULTS: Patients had a
mean age of 65 years and were predominantly female (54%). The mean forced vital
capacity (FVC) % predicted was 73 and the mean diffusing capacity for carbon
monoxide (DLCO) % predicted was 55. Twenty-four percent of the 236 patients with
a high-resolution computed tomography scan available for review had a definite
UIP pattern. The original GAP model, including gender, age, FVC%, and DLCO%, had
a c-index of 0.746 in our cohort. Calibration of this model was satisfactory at
1, 2 and 3 years. Model discrimination was not meaningfully improved by adding
other clinical variables. CONCLUSION: The GAP model that was derived for IPF
performs similarly as a mortality risk prediction tool in RA-ILD.
PMID- 28502423
TI - Advanced functional materials in solid phase extraction for ICP-MS determination
of trace elements and their species - A review.
AB - For the determination of trace elements and their species in various real samples
by inductively coupled plasma mass spectrometry (ICP-MS), solid phase extraction
(SPE) is a commonly used sample pretreatment technique to remove complex matrix,
pre-concentrate target analytes and make the samples suitable for subsequent
sample introduction and measurements. The sensitivity, selectivity/anti
interference ability, sample throughput and application potential of the
methodology of SPE-ICP-MS are greatly dependent on SPE adsorbents. This article
presents a general overview of the use of advanced functional materials (AFMs) in
SPE for ICP-MS determination of trace elements and their species in the past
decade. Herein the AFMs refer to the materials featuring with high adsorption
capacity, good selectivity, fast adsorption/desorption dynamics and satisfying
special requirements in real sample analysis, including nanometer-sized
materials, porous materials, ion imprinting polymers, restricted access materials
and magnetic materials. Carbon/silica/metal/metal oxide nanometer-sized
adsorbents with high surface area and plenty of adsorption sites exhibit high
adsorption capacity, and porous adsorbents would provide more adsorption sites
and faster adsorption dynamics. The selectivity of the materials for target
elements/species can be improved by using physical/chemical modification, ion
imprinting and restricted accessed technique. Magnetic adsorbents in conventional
batch operation offer unique magnetic response and high surface area-volume ratio
which provide a very easy phase separation, greater extraction capacity and
efficiency over conventional adsorbents, and chip-based magnetic SPE provides a
versatile platform for special requirement (e.g. cell analysis). The performance
of these adsorbents for the determination of trace elements and their species in
different matrices by ICP-MS is discussed in detail, along with perspectives and
possible challenges in the future development.
PMID- 28502424
TI - Redox speciation of iron, manganese, and copper in cerebrospinal fluid by strong
cation exchange chromatography - sector field inductively coupled plasma mass
spectrometry.
AB - A new method of simultaneous redox speciation of iron (II/III), manganese
(II/III), and copper (I/II) in cerebrospinal fluid (CSF) has been designed. For
the separation of redox species strong cation exchange chromatography (SCX) with
isocratic elution was employed. Species were detected using inductively coupled
plasma sector field mass spectrometry (ICP-sf-MS), operating at medium
resolution. The following parameters were optimized: analytical column, eluent
composition and pH, CSF injection volume and dilution factor. Analytical column
Dionex IonPac CS5A RFIC 4*250 mm was found to retain and separate species of
interest the most effectively under the isocratic elution with a buffer,
containing 50 mM ammonium citrate, 7.0 mM pyridine-2,6-dicarboxylic acid at pH =
4.2 and flow rate of 0.8 L min-1. Injection volume of 50 MUL with CSF sample
dilution of 1/3 (v/v) with the eluent was shown to result in minimal matrix
suppression. For species identification, retention time matching with standards
was used. The stability of metalloproteins (ferritin, transferrin, and
ceruloplasmin) under elution conditions was evaluated. For the quantification of
redox species, external calibration was employed. To avoid column contamination,
a blank was run after measurement and all quantification values were blank
subtracted. For recovery checks, species quantification data was verified against
total content of an element, measured by dynamic reaction cell ICP-MS. Recoveries
(sum of quantified species vs. total element determinations) were 82.5 +/- 22%
(Mn), 92 +/- 11% (Fe), and 88.7 +/- 12% (Cu). The method was tested using 38 real
CSF samples. Limits of detection (3sigma) for the CSF samples were 0.5 MUg L-1,
0.6 MUg L-1, and 0.8 MUg L-1 for Fe, Mn, and Cu species, respectively. Retention
time precision was 1-7.5% (as RSD), whereas peak area RSDs were in the range 5
11%, both depending on the species.
PMID- 28502425
TI - Resonance energy transfer based electrochemiluminescence and fluorescence sensing
of riboflavin using graphitic carbon nitride quantum dots.
AB - Graphitic carbon nitride quantum dots (g-CNQDs) are rarely used in the field of
electrochemiluminescence. In this paper, g-CNQDs have a strong and stable
electrochemiluminescence (ECL) signal generated in the presence of co-reactant
K2S2O8. The ECL signal of g-CNQDs was quenched by the mechanism of resonance
energy transfer (RET) between donor g-CNQDs and receptor riboflavin (RF) that is
proved by UV-vis absorption spectroscopy, electrochemiluminescence and
fluorescence emission spectroscopy analysis technology. Therefore, we achieved
detection of the riboflavin content in the drug tablets of vitamin B2 using ECL
and FL. The determination results of ECL showed that the riboflavin content of
the drug vitamin B2 (VB2) tablets was consistent with the fluorescence (FL)
analysis, with wider linear range of 0.02-11 MUM and lower minimum detection
limit of 0.63 nM (S/N = 3) than FL. Hence, the riboflavin content in human serum
was further detected using ECL. The relative standard deviation is less than
6.5%, with an acceptable recovery of 95.33%-104.22%, which means that this sensor
has potential applications in the actual sample analysis. As a new ECL luminary,
g-CNQDs have opened a new field for the development and application of ECL
sensor.
PMID- 28502427
TI - Metal-organic aerogel as a coating for solid-phase microextraction.
AB - An iron-based metal-organic aerogel was synthesized using metal-organic framework
nanoparticles and applied as a fiber coating for solid-phase microextraction
(SPME). Chemical, thermal and morphological characteristics of the material were
investigated. Headspace SPME followed by gas chromatography-electron capture
detection was used for the determination of chlorobenzenes in the environmental
samples. The key experimental factors affecting the extraction efficiency of the
analytes, such as ionic strength, extraction and desorption temperature, and
extraction time were investigated and optimized. The applicability of the coating
for the extraction of chlorobenzenes from the environmental samples including
river and tap water, sludge, and coastal soil was evaluated. The detection limits
were in the range of 0.1-60 ng L-1. The relative standard deviations were between
2.0 and 5.0%. The extraction recovery of the analytes was in the range of 88
100%. Compared to the commercial PDMS fiber, the present fiber showed better
extraction efficiency.
PMID- 28502426
TI - Construction and optimization of an efficient breathing-based isothermal emulsion
amplification method.
AB - The reaction temperature is one of the main factors that affect the stability of
emulsion PCR (emPCR). Focusing on this point, we applied the "DNA breathing"
mechanism in BEAMing (Bead, Emulsion, Amplification, and Magnetic) and proposed a
more stable emulsion amplification method. Compared to the conventional emPCR,
this method provided excellent results. Firstly, more stable emulsion system
resulted in higher percentage of single-molecular amplifications (73.17%).
Secondly, an ordinary temperature-controlling device was enough. Our outcome
showed that the reaction temperature of this method was not strict so that the
ordinary temperature-controlling device was enough for it (the heat block sets
vs. the PCR instrument: 13.140 +/- 0.110 vs. 13.008 +/- 0.039, P = 0.120).
Thirdly, the single-biotinylated emP1 coated streptavidin beads were stable
enough to be used for this method (the control temperature vs. the reaction
temperature: 2967.91 +/- 409.045 vs. 3026.22 +/- 442.129, P = 0.334), which could
replace the double-biotinylated emP1 coated beads and was benefit for saving
cost. In conclusion, the method presented here with stable emulsion system,
simplified temperature-controlling device, and decreased investment would be a
highly streamlined and inexpensive option for future single-molecular
amplification based researches.
PMID- 28502429
TI - Quantification of monohydroxylated polycyclic aromatic hydrocarbons in human
urine samples using solid-phase microextraction coupled with glass-capillary
nanoelectrospray ionization mass spectrometry.
AB - Polycyclic aromatic hydrocarbons (PAHs) are environmental contaminants with
carcinogenic effect raising worldwide concerns. Hydroxylated PAHs (OH-PAHs) could
be formed in the body as metabolites of PAHs in human urine samples and thus
considered as biomarkers of PAH exposure. In this study, five OH-PAHs including 3
phenanthrol, 1-naphthol, 2-hydroxy fluorene, 1-hydroxprene and 6-hydroxy chrysene
in human urine samples were selectively enriched by C18 solid-phase
microextraction (SPME), then SPME fiber was connected high voltage and then was
inserted into a glass-capillary to elute and ionize the analytes for mass
spectrometric (MS) detection. The coupling of SPME-MS showed excellent analytical
performance for detection of urinary OH-PAHs under optimal conditions, providing
an easy operation for rapid detection of a single sample within minutes. By use
of internal standard (i.e., 2-hydroxy fluorene-d9), the limit of detection (LOD)
and limit of quantitation (LOQ) of OH-PAHs were found to be less than 0.05 ng L-1
level (S/N > 3) and less than 0.1 ng L-1 level (S/N > 10), respectively. The
dynamic ranges of five OH-PAHs were found to be a range at 0.1-5.0 ng L-1 with
excellent coefficient (R2 > 0.99). This method also showed good precisions (intra
day: 3.4-5.5%, inter-day: 7.0-9.8%, n = 5) and good accuracy (85.3-95.3%, n = 5).
Moreover, ion suppression and matrix effect in detection of OH-PAHs in urine were
also investigated. Human urine samples collected from 12 volunteers including 6
non-smokers and 6 smokers have been successfully analyzed, it was found that
individual OH-PAHs in smokers were higher than in non-smokers. This study
demonstrated that SPME coupled with glass-capillary nanoESI-MS is a sensitive
method for rapid detection of urinary OH-PAHs for health risk assessment of PAHs
exposure.
PMID- 28502428
TI - Non-proximate mass spectrometry using a heated 1-m long PTFE tube and an air
tight APCI ion source.
AB - Direct and rapid trace-level gas analysis is highly needed in various fields such
as safety and security, quality control, food analysis, and forensic medicine. In
many cases, the real samples are bulky and are not accessible to the space
limited ion source of the mass spectrometer. In order to circumvent this problem,
we developed an airtight atmospheric-pressure chemical ionization (APCI) ion
source equipped with a flexible 1-m-long, 2-mm-i.d. PTFE sniffing tube. The
ambient air bearing sample gas was sucked into the heated PTFE tube (130 degrees
C) and was transported to the air-tight ion source without using any extra
pumping system or a Venturi device. Analytes were ionized by an ac corona
discharge located at 1.5 mm from the inlet of the mass spectrometer. By using the
airtight ion source, all the ionized gas in the ion source was introduced into
the vacuum of the mass spectrometer via only the evacuation of the mass
spectrometer (1.6 l min-1). Sub-pg limits of detection were obtained for carbaryl
and trinitrotoluene. Owing to its flexibility and high sensitivity, the sniffing
tube coupled with a mass spectrometer can be used as the stethoscope for the high
sensitive gas analysis. The experimental results obtained for drugs, hydrogen
peroxide and small alkanes were discussed by DFT calculations.
PMID- 28502430
TI - Screening of unapproved drugs using portable Raman spectroscopy.
AB - We present a four-step screening approach for unapproved drugs. The screening
approach is both qualitative and quantitative in design in order to determine if
the sample under study contains the correct and acceptable amount of the declared
active pharmaceutical ingredient. Four commercially-available unapproved
antibiotic and antiviral drugs were used in this study. Out of the 40 individual
samples tested, 100% of the samples matched for the declared active
pharmaceutical ingredient with no false positives. Following this qualitative
identification step, a quantitative assay was used to determine the potency of
the product. The assay involves dissolving the sample in water and using a
partial least squares model to predict the potency of the product. The average
Raman potency results for the four products tested were compared with
chromatographic reference methods and the spectroscopic data were found to be
within ~1-6% of those obtained with the reference method for the four products
tested. The results indicate that aqueous-based Raman assays may be a suitable
field-deployable alternative to traditional techniques run in a laboratory
environment.
PMID- 28502431
TI - A novel photoelectrochemical immunosensor by integration of nanobody and ZnO
nanorods for sensitive detection of nucleoside diphosphatase kinase-A.
AB - Nucleoside diphosphatase kinase A (NDPK-A) is a metastasis-suppressor protein and
a biomarker that act on a wide range cancer cells to inhibit the potential
metastasis. Herein, we present a simple photoelectrochemical immunosensor based
on ZnO nanorod arrays for the sensitive detection of NDPK-A. The ZnO nanorod
arrays cosensitized with CdS nanoparticles and Mn2+ displayed a high and stable
photocurrent response under irradiation. After anti-NPDK-A nanobodies were
immobilized to the ZnO nanorod arrays, the proposed immunosensor can be utilized
for detecting NPDK-A by monitoring the changes in the photocurrent signals of the
electrode resulting from immunoreaction. Accordingly, the well-designed
immunosensor exhibited a low limit of detection (LOD) of 0.3 pg mL-1 and a wide
linear range from 0.5 pg mL-1 to 10 MUg mL-1. The R2 of the regression curve is
0.99782. Meanwhile, the good stability, reproducibility and specificity of the
resulting photoelectrochemical biosensor are demonstrated. In addition, the
presented work would offer a novel and simple approach for the detection of
immunoreactions and provide new insights in popularizing the diagnosis of NPDK-A.
PMID- 28502432
TI - Carbon dots for fluorescent detection of alpha-glucosidase activity using enzyme
activated inner filter effect and its application to anti-diabetic drug
discovery.
AB - Recently, alpha-glucosidase inhibitor has been widely used in clinic for diabetic
therapy. In the present study, a facile and sensitive fluorescent assay based on
enzyme activated inner filter effect (IFE) on nitrogen-doped carbon dots (CDs)
was first developed for the detection of alpha-glucosidase. The N-doped CDs with
green emission were prepared by a one-step hydrothermal synthesis and gave the
fluorescence quantum yield of 30%, which were used as the signal output. Through
alpha-glucosidase catalysis, 4-nitrophenol was released from 4-nitrophenyl-alpha
d-glucopyranoside (NGP). Interestingly, the absorption of 4-nitrophenol and the
excitation of CDs were completely overlapping. Due to its great molar
absorptivity, 4-nitrophenol was capable of acting as a powerful absorber to
affect the fluorescent signal of CDs (i.e. IFE). By converting the absorption
signals into fluorescence signals, the facile fluorescence assay strategy could
be realized for alpha-glucosidase activity sensing, which effectively avoided the
complex modification of the surface of CDs or construction of the nanoprobes. The
established IFE-based sensing platform offered a low detection limit of 0.01 U/mL
(S/N = 3). This proposed sensing approach has also been expanded to the inhibitor
screening and showed excellent applicability. As a typical alpha-glucosidase
inhibitor, acarbose was investigated with a low detection limit of 10-8 M. This
developed method enjoyed many merits including simplicity, lost cost, high
sensitivity, good reproducibility and excellent selectivity, which also provided
a new insight on the application of CDs to develop the facile and sensitive
biosensor.
PMID- 28502433
TI - Eosinophilic Gastrointestinal Disorders.
AB - Eosinophilic esophagitis (EoE) is an atopic disease that is characterized by an
isolated infiltration of eosinophils into the epithelium of the esophagus and is
triggered by specific allergens. Patients should undergo an upper endoscopy with
biopsy after 6 to 8 weeks of treatment with a proton pump inhibitor in order to
make the diagnosis of EoE. Eosinophilic gastroenteritis is a pathologic
eosinophilic infiltration of any portion of the gastrointestinal tract, and
eosinophilic proctocolitis is an eosinophilic infiltration in the colon alone.
PMID- 28502434
TI - Gastroesophageal Reflux Disease.
AB - Gastroesophageal reflux (GER) is a normal physiologic process. It is important to
distinguish GER from GER disease (GERD) since GER does not require treatment.
Although a diagnosis of GERD can largely be based on history and physical alone,
endoscopy and pH impedance studies can help make the diagnosis when there in
atypical presentation. In children and adolescents, lifestyle changes and acid
suppression are first-line treatments for GERD. In infants, acid suppression is
not effective, but a trial of hydrolyzed formula can be considered, as milk
protein sensitivity can be difficult to differentiate from GER symptoms.
PMID- 28502435
TI - Caustic Ingestions and Foreign Bodies Ingestions in Pediatric Patients.
AB - Children inevitably swallow foreign material accidentally or intentionally. Each
type of ingestion carries their own set of risks and complications, short and
long term, some requiring immediate attention while others close monitoring.
Alkalotic household cleaning products and lithium button batteries are
increasingly common and damage the esophagus quickly. While many toys with rare
earth metals are banned, they are already present in many households and can
cause necrosis of bowel that is between the magnets. This article reviews the
incidence and assessment along with current literature to provide guidelines for
management of pediatric patients with suspected caustic or foreign body
ingestion.
PMID- 28502436
TI - Abdominal Pain in Children: From the Eternal City to the Examination Room.
AB - Abdominal pain is a common presenting symptom in children. The differential
diagnosis of abdominal pain is extensive; however, a vast majority of patients
ultimately are diagnosed with functional abdominal pain disorders. Functional
gastrointestinal disorders are defined using the recently released Rome IV
criteria. These are not diagnoses of exclusion. If there are no alarm signs, the
diagnosis may be made with a focused evaluation. Treatment of these disorders
requires a biopsychosocial approach to the disorder and an individualized and
multipronged treatment plan.
PMID- 28502437
TI - Gastrointestinal Bleeding and Management.
AB - There is a broad clinical spectrum of gastrointestinal bleeding in children,
ranging from subtle laboratory findings to dramatic clinical presentations. This
review provides a framework for the evaluation and management of gastrointestinal
hemorrhage for pediatricians. It outlines strategies for obtaining a tailored
patient history and conducting a thorough physical examination that can shed
light on the location, severity, and likely etiology of bleeding. It appraises
blood tests, radiologic tools, and endoscopic modalities frequently used to
identify and control a source of bleeding.
PMID- 28502439
TI - Pediatric Inflammatory Bowel Disease.
AB - Inflammatory bowel disease (IBD), including Crohn disease, ulcerative colitis,
and IBD-unspecified, is a chronic immune-mediated condition of the
gastrointestinal tract in which the goal of treatment is to induce and maintain
durable remission. In pediatrics, there is a wide spectrum of presenting
symptoms, but esophagogastroduodenoscopy and colonoscopy are imperative to
confirming the diagnosis. Treatment goals include achieving mucosal healing of
the gastrointestinal tract, reaching growth potential, limiting medication
toxicities, and optimizing quality of life for all patients.
PMID- 28502438
TI - Celiac Disease and Nonceliac Gluten Sensitivity.
AB - Gluten-related disorders include celiac disease (CD), wheat allergy, and
nonceliac gluten sensitivity. CD is an autoimmune enteropathy caused by damage to
small intestinal mucosa when gluten is ingested in genetically susceptible
individuals. Currently, the only available treatment of CD is gluten-free diet.
Several potential treatments are being researched. Wheat allergy is a
hypersensitivity reaction caused by IgE-mediated and/or non-IgE-mediated immune
response, and can involve the gastrointestinal tract, skin, or respiratory tract.
Nonceliac gluten sensitivity is one of a variety of immunologic, morphologic, or
symptomatic manifestations precipitated by ingestion of gluten in individuals in
whom CD and wheat allergy are excluded.
PMID- 28502440
TI - Motility Disorders in Children.
AB - Gastrointestinal motility disorders in the pediatric population are common and
can range from benign processes to more serious disorders. Performing and
interpreting motility evaluations in children present unique challenges. There
are primary motility disorders but abnormal motility may be secondary due to
other disease processes. Diagnostic studies include radiographic scintigraphic
and manometry studies. Although recent advances in the genetics, biology, and
technical aspects are having an important impact and have allowed for a better
understanding of the pathophysiology and therapy for gastrointestinal motility
disorders in children, further research is needed to be done to have better
understanding of the pathophysiology and for better therapies.
PMID- 28502441
TI - Intestinal Transplant in Children.
AB - The past decade has seen major advances in the field of transplantation; it is
the treatment of choice for many with intestinal failure. One-year mortality from
pediatric intestinal transplantation has significantly declined, from 30% to 10%
to 15% nationally, mainly due to a multidisciplinary approach in transplant
centers. Pediatric age carries special considerations along the spectrum of care
that continue to cause challenges but also offers growth opportunities. Pediatric
intestinal transplantation indications and timing are changing as a result of new
developments in diagnostic and treatment tools. This article reviews updates on
pediatric intestinal transplantation and highlights future directions.
PMID- 28502442
TI - Neonatal Cholestasis.
AB - Neonatal jaundice is common and usually not concerning when it is secondary to
unconjugated hyperbilirubinemia, below the neurotoxic level, and resolves early.
Primary care providers should be vigilant, however, about evaluating infants in
whom jaundice presents early, is prolonged beyond 2 weeks of life, or presents at
high levels. Even in well-appearing infants, fractionated (direct and indirect)
bilirubin levels should be obtained in these clinical scenarios to evaluate for
potential cholestasis. This review presents an approach to the evaluation of a
jaundiced infant and discusses diagnosis and management of several causes of
neonatal cholestasis.
PMID- 28502445
TI - Pediatric Liver Transplantation.
AB - Excellent outcomes over the last 3 decades have made liver transplantation the
treatment of choice for many advanced liver disorders. This success also opened
liver transplantation to new indications such as liver tumors and metabolic
disorders. The emergence of such new indications for liver transplantation is
bringing a new stream of patients along with disease-specific challenges. The
cumulative number of liver transplant recipients is peaking, requiring novel
systems of health care delivery that meet the needs of this special patient
population. This article reviews updates and new development in pediatric liver
transplantation.
PMID- 28502444
TI - Nonalcoholic Fatty Liver Disease in Children: Hepatic and Extrahepatic
Complications.
AB - Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation
of metabolic syndrome and has become the most common form of chronic liver
disease in children and adolescents. The histologic spectrum of NAFLD is broad
ranging, from the relatively benign form of simple steatosis to the aggressive
form of nonalcoholic steatohepatitis, eventually leading to fibrosis and
cirrhosis. NAFLD has also been recognized as an independent risk factor for
extrahepatic complications, such as cardiovascular disease, type 2 diabetes
mellitus, sleep disorders, and osteoporosis. In this review, we discuss both the
hepatic and extrahepatic complications of NAFLD in children.
PMID- 28502443
TI - Hepatitis B and C.
AB - Chronic viral hepatitis is a global health threat and financial burden. Hepatitis
B and C viruses (HBV and HCV) are the most common causes of chronic viral
hepatitis in the United States. Most cases are asymptomatic before adulthood.
Research has resulted in effective therapy for HCV and the promise of effective
therapies for HBV. For HCV, therapy is pegylated interferon and ribavirin.
Clinical trials with effective direct-acting antiviral agents are underway in
pediatrics. For HBV, approved agents are alpha-interferon, lamivudine, adefovir,
tenofovir, and entecavir. However, treatment seldom results in functional cure
and more effective therapies are urgently needed.
PMID- 28502447
TI - The Transition of the Gastrointestinal Patient from Pediatric to Adult Care.
AB - Transition is the long process of developing independent self-management skills
whereas transfer is the actual move from pediatric to adult-centered provider.
Structured anticipated transition works best with timelines of tasks to master
and discussion of the stylistic differences between pediatric and adult
practices. Disease-specific issues need to be addressed, such as earlier
timelines for diet-based therapies, parental support for critical illnesses, and
differences in therapeutic strategies.
PMID- 28502448
TI - The Remarkable Gastrointestinal Tract.
PMID- 28502446
TI - Pancreatic Disorders.
AB - Once considered uncommon, pancreatic diseases are increasingly recognized in the
pediatric age group. Acute pancreatitis, acute recurrent pancreatitis, and
chronic pancreatitis occur in children with an incidence approaching that of
adults. Risk factors are broad, prompting the need for a completely different
diagnostic and therapeutic approach in children. Although cystic fibrosis remains
the most common cause of exocrine pancreatic insufficiency, other causes such as
chronic pancreatitis may be as common as Shwachman Diamond syndrome. Long-term
effects of pancreatic diseases may be staggering, as children suffer from
significant disease burden, high economic cost, nutritional deficiencies,
pancreatogenic diabetes, and potentially pancreatic cancer.
PMID- 28502449
TI - Pediatric Gastroenterology.
PMID- 28502450
TI - In This Issue....
PMID- 28502452
TI - The impact of submarine copper mine tailing disposal from the 1970s on
Repparfjorden, northern Norway.
AB - We investigate the state of sedimentological environment and contaminant status
of Repparfjorden (N Norway) impacted by submarine disposal of mine tailings
during the 1970s using sedimentological and geochemical properties of seventeen
sediment cores. The impact of tailings disposal is mainly restricted to the inner
fjord where the discharge occurred. Sediment cores retrieved from the inner fjord
contain layers of mine tailings up to 9-cm thick, 3-9cm below the seafloor.
Spreading of the tailing-related metal Cu and particles is limited to the inner
fjord and to a 2cm layer in one core from the outer fjord. Two interrelated
factors, fjord morphology and sedimentation rate, controlled the distribution of
contaminant-laden tailings in the fjord. The mobility of Cu from buried
contaminated sediments to the sediment-water interface in the inner fjord
indicates that benthic communities have been continuously exposed to elevated Cu
concentrations for nearly four decades.
PMID- 28502451
TI - Benefits and shortcomings of non-destructive benthic imagery for monitoring hard
bottom habitats.
AB - Hard-bottom habitats with complex topography and fragile epibenthic communities
are still not adequately considered in benthic monitoring programs, despite their
potential ecological importance. While indicators of ecosystem health are defined
by major EU directives, methods commonly used to measure them are deficient in
quantification of biota on hard surfaces. We address the suitability of seafloor
imaging for monitoring activities. We compared the ability of high-resolution
imagery and physical sampling methods (grab, dredge, SCUBA-diving) to detect
taxonomic and functional components of epibenthos. Results reveal that (1) with
minimal habitat disturbance on large spatial scales, imagery provides valuable,
cost-effective assessment of rocky reef habitat features and community structure,
(2) despite poor taxonomic resolution, image-derived data for habitat-forming
taxa might be sufficient to infer richness of small sessile and mobile fauna, (3)
physical collections are necessary to develop a robust record of species
richness, including species-level taxonomic identifications, and to establish a
baseline.
PMID- 28502453
TI - Petroleum hydrocarbon toxicity to corals: A review.
AB - The proximity of coral reefs to coastal urban areas and shipping lanes
predisposes corals to petroleum pollution from multiple sources. Previous
research has evaluated petroleum toxicity to coral using a variety of
methodology, including monitoring effects of acute and chronic spills, in situ
exposures, and ex situ exposures with both adult and larval stage corals.
Variability in toxicant, bioassay conditions, species and other methodological
disparities between studies prevents comprehensive conclusions regarding the
toxicity of hydrocarbons to corals. Following standardized protocols and
quantifying the concentration and composition of toxicant will aid in comparison
of results between studies and extrapolation to actual spills.
PMID- 28502454
TI - Seasonal and spatial variations of marine litter on the south-eastern Black Sea
coast.
AB - The south-eastern Black Sea coast in Turkey was evaluated for marine litter
composition and density covering nine beaches during four seasons. The marine
litter (>2cm in size), was collected from the coast and categorized into material
and usage categories. The data analysis showed that plastic was the most abundant
litter (>=61.65%) by count and weight followed by styrofoam and fabric. The
marine litter density ranged from 0.03 to 0.58 with a mean (+/-SD) of 0.16+/-0.02
items/m2 by count. Based on weight, it varied between 0.44 and 14.74g/m2 with
3.35+/-1.63. The east side had a higher marine litter density than the west side
with significant differences between beaches. The variations due to different
seasons were not significant for any beach. The results of this study should
provide baseline information about the coastal marine pollution and will assist
the mitigation strategies.
PMID- 28502455
TI - Seasonal changes in stress biomarkers of an exotic coastal species - Chaetopleura
angulata (Polyplacophora) - Implications for biomonitoring.
AB - Knowledge on baseline values of stress biomarkers in natural conditions is urgent
due to the need of reference values for monitoring purposes. Here we assessed the
cellular stress response of the chiton Chaetopleura angulata in situ. Biomarkers
commonly used in environmental monitoring (heat shock protein 70kDa, total
ubiquitin, catalase, glutathione-S-transferase, superoxide-dismutase, lipid
peroxidation) were analyzed in the digestive system, gills and muscle of C.
angulata, under spring and summer conditions in order to assess seasonal tissue
specific responses. Season had an effect on all targeted organs, especially
affecting the digestive system which displayed clear seasonal clusters. The
respective Integrated Biomarker Response (IBR) showed a 7.2-fold seasonal
difference. Muscle and gills showed similar IBRs between seasons making them
appropriate organs to monitor chemical pollution as they were less responsive to
seasonal variation. The most stable biomarkers in these organs were ubiquitin and
superoxide-dismutase thus being reliable for monitoring purposes.
PMID- 28502456
TI - Successful Team-Based Management of Renal Cell Carcinoma With Caval Extension of
Tumor Thrombus Above the Diaphragm.
PMID- 28502457
TI - Anesthesia for Pulmonary Endarterectomy and Extracorporeal Membrane Oxygenation
in a Patient With Achondroplasia.
PMID- 28502458
TI - Acute Pulmonary Hemorrhage Following Radiofrequency Ablation of Atrial
Fibrillation.
PMID- 28502459
TI - Discovery of indolin-2-one derivatives as potent PAK4 inhibitors: Structure
activity relationship analysis, biological evaluation and molecular docking
study.
AB - Utilizing a pharmacophore hybridization approach, a novel series of substituted
indolin-2-one derivatives were designed, synthesized and evaluated for their in
vitro biological activities against p21-activated kinase 4. Compounds 11b, 12d
and 12g exhibited the most potent inhibitory activity against PAK4 (IC50=22nM,
16nM and 27nM, respectively). Among them, compound 12g showed the highest
antiproliferative activity against A549 cells (IC50=0.83MUM). Apoptosis analysis
in A549 cells suggested that compound 12g delayed cell cycle progression by
arresting cells in the G2/M phase of the cell cycle, retarding cell growth.
Further investigation demonstrated that compound 12g strongly inhibited migration
and invasion of A549 cells. Western blot analysis indicated that compound 12g
potently inhibited the PAK4/LIMK1/cofilin signalling pathways. Finally, the
binding mode between compound 12g with PAK4 was proposed by molecular docking. A
preliminary ADME profile of the compound 12g was also drawn on the basis of
QikProp predictions.
PMID- 28502461
TI - Meta-Analysis of Effects of Voluntary Slow Breathing Exercises for Control of
Heart Rate and Blood Pressure in Patients With Cardiovascular Diseases.
AB - Rising heart rate (HR) and elevated blood pressure (BP) cause a greater frequency
of cardiovascular events. Many patients cannot maintain target HR and BP using
pharmacological therapies. To evaluate the effectiveness of voluntary slow
breathing exercises in reducing resting HR and BP, we searched Embase (1974 to
April 2016), PubMed (1966 to April 2016), the Cochrane Central Register of
Controlled Trials (issue 4, April 2016), and PEDro (www.pedro.org.au; 1999 to
April 2016). The primary outcome was the mean change in HR at rest. Secondary
outcomes included changes in systolic blood pressure (SBP) and diastolic blood
pressure (DBP) as well as compliance with the breathing training. Finally, we
included 6 studies consisting of 269 subjects. Practice of the breathing
exercises resulted in statistically significant HR reduction (mean difference:
1.72 beats/min, 95% CI -2.70 to -0.75). Reductions were seen in SBP (mean
difference: -6.36 mm Hg, 95% CI -10.32 to -2.39) and DBP (mean difference: -6.39
mm Hg, 95% CI -7.30 to -5.49) compared with the controls. Trial durations ranged
from 2 weeks to 6 months. In conclusion, the existing evidence from randomized
controlled trails demonstrates that short-term voluntary slow breathing exercises
can reduce resting HR, SBP, and DBP for patients with cardiovascular diseases.
PMID- 28502460
TI - Can the Use of Bone Marrow Parameters Improve the Efficacy of Risk Prediction
Scores in Chronic Myeloid Leukemia in Imatinib Era?
AB - INTRODUCTION: Many attempts have been made to develop risk prediction scores for
chronic myeloid leukemia in chronic phase (CML-CP) to identify the subgroup with
a poorer response to therapy to enable early intensification of treatment.
Because the bone marrow (BM) provides a more sensitive reflection of the disease
process, we hypothesized that using BM parameters in the Sokal and European
Treatment and Outcome Study (EUTOS) risk scores could improve their efficacy in
an imatinib-treated population. MATERIALS AND METHODS: We analyzed cases of CML
CP for their response and survival outcomes with imatinib using risk groupings
determined by the Sokal and EUTOS scores using peripheral blood (PB) or BM
parameters (Sokal-PB, Sokal-BM, EUTOS-PB, and EUTOS-BM). RESULTS: A total of 371
cases were analyzed. The concordance for risk groups was greater for the EUTOS
scores (81.9%) than for the Sokal scores (68.1%) using PB versus BM parameters.
For all 4 risk scores, the predictive efficacy was statistically significant.
EUTOS-PB and EUTOS-BM could better prognosticate for progression-free survival
(PFS) and overall survival (OS) between the low- and high-risk groups (P <
.0001). However, with the Sokal risk score, the use of BM parameters improved the
prognostic capacity for PFS between the low- and intermediate-risk groups, with a
statistically significant difference (P = .025), but not for OS (P = .88).
CONCLUSION: The use of BM parameters, a simple method that is feasible in routine
clinical practice could improve the prognostic efficacy of the Sokal score for
PFS but not for OS in low- and intermediate-risk groups. Further research to
improve the sensitivity of risk scores for CML-CP prognosis and attempts at risk
directed therapy is warranted.
PMID- 28502463
TI - Greening the Radiology Department: Not a Big Mountain to Climb.
AB - An environmental-friendly radiology department should be a requirement of the
future era. The aim of this article is to make radiologists aware of their
responsibilities for a greener world. We have suggested a number of minor but
important changes in various sections of a radiology department that can make the
radiology department more environmentally friendly. These small steps require
relatively little effort on our part but cumulatively, may have a huge positive
impact on our environment.
PMID- 28502462
TI - Radiology Exposure in the Undergraduate Curriculum: A Medical Student Perspective
on Quality and Opportunities for Positive Change.
AB - PURPOSE: This article is a continuation of a qualitative study designed to
explore how radiology exposures can impact medical student opinions and
perceptions of radiology and radiologists. We focused on: 1) conducting a
radiology exposure inventory from the perspective of the medical student; 2)
student evaluation of the quality of the radiology exposures and suggestions for
positive change; and 3) development of a framework to address the needs of
medical students as it relates to radiology education in the undergraduate
medical curriculum. METHODS: Research methodology and design for this qualitative
study were described in detail in a previous article by Visscher et al [1].
RESULTS: Participants included 28 medical students; 18 were in medical school
years 1 and 2 (preclerkship), and 10 were in years 3 and 4 (clerkship). Specific
to the focus of this article, the data revealed 3 major findings: 1) multiple
exposures to radiology exist, and they are received and valued differently
depending on the medical student's stage of professional development; 2) medical
students value radiology education and want their radiology exposure to be
comprehensive and high quality; 3) Medical students have constructive suggestions
for improving the quality of both formal and informal radiology exposures.
CONCLUSIONS: Performing a radiology exposure inventory from a medical student
perspective is a useful way to explore how students receive and value radiology
instruction. Medical students want a more comprehensive radiology education that
can be summarized using the 5 C's of Radiology Education framework. The 5 C's
(curriculum, coaching, collaborating, career and commitment) reflect medical
students' desires to learn content that will support them in clinical practice,
be supported in their professional development, and have the necessary
information to make informed career decisions.
PMID- 28502464
TI - Small signs, important diagnoses.
PMID- 28502465
TI - Application of NMR to studies of intrinsically disordered proteins.
AB - The prevalence of intrinsically disordered protein regions, particularly in
eukaryotic proteins, and their clear functional advantages for signaling and gene
regulation have created an imperative for high-resolution structural and
mechanistic studies. NMR spectroscopy has played a central role in enhancing not
only our understanding of the intrinsically disordered native state, but also how
that state contributes to biological function. While pathological functions
associated with protein aggregation are well established, it has recently become
clear that disordered regions also mediate functionally advantageous assembly
into high-order structures that promote the formation of membrane-less sub
cellular compartments and even hydrogels. Across the range of functional assembly
states accessed by disordered regions, post-translational modifications and
regulatory macromolecular interactions, which can also be investigated by NMR
spectroscopy, feature prominently. Here we will explore the many ways in which
NMR has advanced our understanding of the physical-chemical phase space occupied
by disordered protein regions and provide prospectus for the future role of NMR
in this emerging and exciting field.
PMID- 28502466
TI - Purification and site-directed mutagenesis of linoleate 9S-dioxygenase-allene
oxide synthase of Fusarium oxysporum confirms the oxygenation mechanism.
AB - Plants and fungi form jasmonic acid from alpha-linolenic acid. The first two
steps of biosynthesis in plants occur by sequential transformation by 13S
lipoxygenase and allene oxide synthase (AOS). The biosynthesis in fungi may
follow this classical scheme, but the only fungal AOS discovered so far are
cytochromes P450 (CYP) fused to 8- and 9-dioxygenases (DOX). In the present
report, we purified recombinant 9S-DOX-AOS of Fusarium oxysporum from cell lysate
by cobalt affinity chromatography to near homogeneity and studied key residues by
site-directed mutagenesis. Sequence homology with 8R-DOX-linoleate diol synthases
(8R-DOX-LDS) suggested that Tyr414 catalyzes hydrogen abstraction and that
Cys1051 forms the heme thiolate ligand. Site-directed mutagenesis (Tyr414Phe;
Cys1051Ser) led to loss of 9S-DOX and 9S-AOS activities, respectively, but other
important residues in the CYP parts of 5,8- and 7,8-LDS or 9R-AOS were not
conserved. The UV-visible spectrum of 9S-DOX-AOS showed a Soret band at 409 nm,
which shifted to 413 nm in the Cys1051Ser mutant. The 9S-AOS of the Tyr414Phe
mutant transformed 9S-hydroperoxides of alpha-linolenic and linoleic acids to
allene oxides/alpha-ketols, but it did not transform 13-hydroperoxides. We
conclude that 9S- and 8R-DOX catalyze hydrogen abstraction at C-11 and C-8,
respectively, by homologous Tyr residues.
PMID- 28502467
TI - Remarks to the debate on mapping heavy metals in soil and soil monitoring in the
European Union.
AB - We provide an overview of the main features of the LUCAS topsoil survey of the EU
in comparison to the GEMAS survey. In addition we describe the policy
requirements and scientific principles of soil monitoring programs.
PMID- 28502468
TI - Magnetically assisted matrix solid phase dispersion for extraction of parabens
from breast milks.
AB - In the present work, magnetically assisted matrix solid phase dispersion (MA
MSPD) was used as an efficient solid phase extraction method. MA-MSPD followed by
a dispersive liquid-liquid microextraction (DLLME) was applied for determination
of parabens in breast milks. The analysis were performed using LC-UV and LC
MS/MS. Poly(indole-thiophene) coated magnetic graphene oxide (MGO@PIT) was
synthesized, characterized and used as the sorbent. Na2SO4 was used as the drying
salt as well as matrix dispersing agent. Exact amounts of MGO@PIT and Na2SO4 were
added into 200MUL volume of the milk and the mixture was gently blended to obtain
a dry powder. The blend was dispersed into ultrapure water and stirred. Because
of dissolving of the matrix dispersant in water, only the magnetic sorbent is
remained into water which can be easily separated by a magnet. Next, the sorbent
was eluted with a suitable solvent to desorb the analyte and the eluent was used
as the disperser solvent for the subsequent DLLME. In this approach, the target
analytes were directly adsorbed on the surface of the magnetic sorbent without
any sample pretreatment. Compared with conventional MSPD, MA-MSPD increases the
simplicity of the extraction procedure, decreases the extraction time and
eliminates the column packing as well as its related drawbacks. The optimum
extraction parameters were obtained as 50mg of MGO@PIT, 550mg of Na2SO4 in 200MUL
of the milk sample, 1.0mL of methanol as the eluent solvent under fierce vortex
for 2.0min and 100MUL of 1-octanol as the extraction solvent. Under the optimal
conditions, the extraction recoveries greater than 83% were obtained, and LOD and
LOQ values were found 25ngmL-1 (about 0.5ngmL-1 by LC-MS/MS) and 50ngmL-1 using
LC-UV, respectively. The calibration curves were in the range of 50-4000ngmL-1
with the determination coefficients (R2) higher than 0.998. Relative standard
deviations (RSD%) for intra- and inter-day precisions were less than 7.5% and
11.3%, respectively. The results confirmed that the proposed method is a rapid,
feasible and convenient technique which makes it suitable for the analysis of
parabens from breast milk samples.
PMID- 28502471
TI - Reference Standards for Gene and Cell Therapy Products.
PMID- 28502469
TI - Hepatocyte Growth Factor Suppresses Inflammation and Promotes Epithelium Repair
in Corneal Injury.
AB - Corneal injuries are among the major causes of ocular morbidity and vision
impairment. Optimal epithelial wound healing is critical for the integrity and
transparency of the cornea after injury. Hepatocyte growth factor (HGF) is a
mitogen and motility factor that primarily regulates epithelial cell function.
Herein, we investigate the effect of HGF on proliferation of corneal epithelial
cells (CECs) in inflamed conditions both in vitro and in vivo. We demonstrate
that HGF not only promotes CEC proliferation in homeostatic conditions but also
reverses the anti-proliferative effect of the inflammatory environment on these
cells. Furthermore, using a mouse model of ocular injury, we show that HGF
treatment suppresses ocular inflammation and actively augments CEC proliferation,
leading to improved and accelerated corneal epithelial repair. These findings
have potential translational implications and could provide a framework for the
development of novel HGF-based therapies for corneal epithelial defects.
PMID- 28502470
TI - Antitumoral Cascade-Targeting Ligand for IL-6 Receptor-Mediated Gene Delivery to
Glioma.
AB - The effective treatment of glioma is largely hindered by the poor transfer of
drug delivery systems across the blood-brain barrier (BBB) and the difficulty in
distinguishing healthy and tumorous cells. In this work, for the first time, an
interleukin-6 receptor binding I6P7 peptide was exploited as a cascade-targeting
ligand in combination with a succinoyl tetraethylene pentamine (Stp)-histidine
oligomer-based nonviral gene delivery system (I6P7-Stp-His/DNA). The I6P7 peptide
provides multiple functions, including the cascade-targeting potential
represented by a combined BBB-crossing and subsequent glioma-targeting ability,
as well as a direct tumor-inhibiting effect. I6P7-Stp-His/DNA nanoparticles (NPs)
mediated higher gene expression in human glioma U87 cells than in healthy human
astrocytes and a deeper penetration into glioma spheroids than scrambled peptide
modified NPs. Transport of I6P7-modified, but not the control, NPs across the BBB
was demonstrated in vitro in a transwell bEnd.3 cell model resulting in
transfection of underlying U87 cells and also in vivo in glioma-bearing mice.
Intravenous administration of I6P7-Stp-His/plasmid DNA (pDNA)-encoding inhibitor
of growth 4 (pING4) significantly prolonged the survival time of orthotopic U87
glioma-bearing mice. The results denote that I6P7 peptide is a roborant cascade
targeting ligand, and I6P7-modified NPs might be exploited for efficient glioma
therapy.
PMID- 28502472
TI - A novel concept for tumour targeting with radiation: Inverse dose-painting or
targeting the "Low Drug Uptake Volume".
AB - BACKGROUND AND PURPOSE: We tested a novel treatment approach combining (1)
targeting radioresistant hypoxic tumour cells with the hypoxia-activated prodrug
TH-302 and (2) inverse radiation dose-painting to boost selectively non-hypoxic
tumour sub-volumes having no/low drug uptake. MATERIAL AND METHODS: 18F-HX4
hypoxia tracer uptake measured with a clinical PET/CT scanner was used as a
surrogate of TH-302 activity in rhabdomyosarcomas growing in immunocompetent
rats. Low or high drug uptake volume (LDUV/HDUV) was defined as 40% of the GTV
with the lowest or highest 18F-HX4 uptake, respectively. Two hours post TH
302/saline administration, animals received either single dose radiotherapy (RT)
uniformly (15 or 18.5Gy) or a dose-painted non-uniform radiation (15Gy) with 50%
higher dose to LDUV or HDUV (18.5Gy). Treatment plans were created using Eclipse
treatment planning system and radiation was delivered using VMAT. Tumour response
was quantified as time to reach 3 times starting tumour volume. RESULTS: Non
uniform RT boosting tumour sub-volume with low TH-302 uptake (LDUV) was superior
to the same dose escalation to HDUV (p<0.0001) and uniform RT with the same mean
dose 15Gy (p=0.0077). Noteworthy, dose escalation to LDUV required on average
3.5Gy lower dose to the GTV to achieve similar tumour response as uniform dose
escalation. CONCLUSIONS: The results support targeted dose escalation to non
hypoxic tumour sub-volume with no/low activity of hypoxia-activated prodrugs.
This strategy applies on average a lower radiation dose and is as effective as
uniform dose escalation to the entire tumour. It could be applied to other type
of drugs provided that their distribution can be imaged.
PMID- 28502473
TI - Salvage radiation therapy after prostatectomy: Understanding the dose-response
effect.
PMID- 28502474
TI - [Role of prostate MRI, TRUS fusion biopsies and new markers in the diagnostic
strategy of prostate cancer].
AB - Multiparametric MRI prostate (mp-MRI) is a powerful tool to locate lesions>0.5cm3
(below this threshold tumor volume, prostate cancers are classified as
"insignificant"). The detection rate of the mp-MRI for significant cancers of
small volume (0.5-1cm3) with a Gleason score>=7 is>85 %. The prostate mp-MRI
optimizes the management of cancers classified as low risk of progression by
providing aggressive criteria for misclassified lesions, which require an active
treatment and enhance the clinicopathological criteria of indolence for
subclinical lesions, which can justify of surveillance. MRI-mp coupled to the 3D
ultrasound image fusion, optimizes the predictive value of biopsies and improves
tumor staging, particularly when benign prostatic hyperplasia (>40cm3) is
associated with clinical course. New tissue markers feasible on biopsies allow to
define better the risk of progression of the small volume of cancer in order to
reinforce the indications of surveillance or delayed curative treatment.
PMID- 28502476
TI - Purkinje Cells Are More Vulnerable to the Specific Depletion of Cathepsin D Than
to That of Atg7.
AB - Neurologic phenotypes of cathepsin D (CTSD)-deficient mice, a murine model of
neuronal ceroid lipofuscinoses, indicate the importance of CTSD for the
maintenance of metabolism in central nervous system neurons. To further
understand the role of CTSD in central nervous system neurons, we generated mice
with a CTSD deficiency specifically in the Purkinje cells (PCs)
(CTSDFlox/Flox;GRID2-Cre) and compared their phenotypes with those of PC
selective Atg7-deficient (Atg7Flox/Flox;GRID2-Cre) mice. In both strains of mice,
PCs underwent degeneration, but the CTSD-deficient PCs disappeared more rapidly
than their Atg7-deficient counterparts. When CTSD-deficient PCs died, the
neuronal cell bodies became shrunken, filled with autophagosomes and
autolysosomes, and had nuclei with dispersed small chromatin fragments. The dying
Atg7-deficient PCs also showed similar ultrastructures, indicating that the
neuronal cell death of CTSD- and Atg7-deficient PCs was distinct from apoptosis.
Immunohistochemical observations showed the formation of calbindin-positive
axonal spheroids and the swelling of vesicular GABA transporter-positive
presynaptic terminals that were more pronounced in Atg7-deficient PCs than in
CTSD-deficient PCs. An accumulation of tubular vesicles may have derived from the
smooth endoplasmic reticulum; nascent autophagosome-like structures with double
membranes was a common feature in the swollen axons of these PCs. These results
suggested that PCs were more vulnerable to CTSD deficiency in lysosomes than to
autophagy impairment, and this vulnerability does not depend on the severity of
axonal swelling.
PMID- 28502475
TI - Cyst-Like Osteolytic Formations in Recombinant Human Bone Morphogenetic Protein-2
(rhBMP-2) Augmented Sheep Spinal Fusion.
AB - Multiple case reports using recombinant human bone morphogenetic protein-2 (rhBMP
2) have reported complications. However, the local adverse effects of rhBMP-2
application are not well documented. In this report we show that, in addition to
promoting lumbar spinal fusion through potent osteogenic effects, rhBMP-2
augmentation promotes local cyst-like osteolytic formations in sheep trabecular
bones that have undergone anterior lumbar interbody fusion. Three months after
operation, conventional computed tomography showed that the trabecular bones of
the rhBMP-2 application groups could fuse, whereas no fusion was observed in the
control group. Micro-computed tomography analysis revealed that the core implant
area's bone volume fraction and bone mineral density increased proportionately
with rhBMP-2 dose. Multiple cyst-like bone voids were observed in peri-implant
areas when using rhBMP-2 applications, and these sites showed significant bone
mineral density decreases in relation to the unaffected regions. Biomechanically,
these areas decreased in strength by 32% in comparison with noncystic areas.
Histologically, rhBMP-2-affected void sites had an increased amount of fatty
marrow, thinner trabecular bones, and significantly more adiponectin- and
cathepsin K-positive cells. Despite promoting successful fusion, rhBMP-2 use in
clinical applications may result in local adverse structural alterations and
compromised biomechanical changes to the bone.
PMID- 28502478
TI - The Cellular Retinoic Acid Binding Protein 2 Promotes Survival of Malignant
Peripheral Nerve Sheath Tumor Cells.
AB - Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive neoplasms that
commonly occur in patients with neurofibromatosis type 1 (NF1). Effective
chemotherapy is not available. To characterize a therapeutic target for
treatment, we investigated the role of cellular retinoic acid binding protein 2
(CRABP2) in MPNST in vitro. CRABP2 is a transcriptional co-activator of retinoic
acid signaling. Although overexpression of CRABP2 is described in several
cancers, it has not yet been studied in MPNSTs. We investigated CRABP2 expression
in cultured Schwann cells and formalin-fixed, paraffin-embedded specimens of
human peripheral nerve sheath tumors. A transient knockdown of CRABP2 was
established in human NF1-associated MPNST cell lines (S462, T265, NSF1), and
functional effects on viability, proliferation, apoptosis, and cytotoxicity were
monitored. Finally, a 45-pathway reporter assay was performed in knockdown cells.
Expression of CRABP2 was found in epithelium, fibroblasts, and tumor Schwann
cells of skin, neurofibromas, and MPNSTs. In contrast, normal skin Schwann cells
(NF1+/-, NF1-/-) did not express CRABP2. In the absence of retinoic acid, MPNST
cells depleted of CRABP2 had reduced viability and proliferation, induction of
apoptosis and cytotoxicity, and up-regulation of the type 1 interferon pathway.
These data suggest a retinoic acid-independent, non-tumor suppressor role of
CRABP2 for the survival of MPNST cells in vitro. Targeting CRABP2 overexpression
may represent a unique approach for the treatment of human MPNSTs.
PMID- 28502477
TI - Knockdown of Hepatic Gonadotropin-Releasing Hormone by Vivo-Morpholino Decreases
Liver Fibrosis in Multidrug Resistance Gene 2 Knockout Mice by Down-Regulation of
miR-200b.
AB - Hepatic fibrosis occurs during the progression of primary sclerosing cholangitis
(PSC) and is characterized by accumulation of extracellular matrix proteins.
Proliferating cholangiocytes and activated hepatic stellate cells (HSCs)
participate in the promotion of liver fibrosis during cholestasis. Gonadotropin
releasing hormone (GnRH) is a trophic peptide hormone synthesized by hypothalamic
neurons and the biliary epithelium and exerts its biological effects on
cholangiocytes by interaction with the receptor subtype (GnRHR1) expressed by
cholangiocytes and HSCs. Previously, we demonstrated that administration of GnRH
to normal rats increased intrahepatic biliary mass (IBDM) and hepatic fibrosis.
Also, miR-200b is associated with the progression of hepatic fibrosis; however,
the role of the GnRH/GnRHR1/miR-200b axis in the development of hepatic fibrosis
in PSC is unknown. Herein, using the mouse model of PSC (multidrug resistance
gene 2 knockout), the hepatic knockdown of GnRH decreased IBDM and liver
fibrosis. In vivo and in vitro administration of GnRH increased the expression of
miR-200b and fibrosis markers. The GnRH/GnRHR1 axis and miR-200b were up
regulated in human PSC samples. Cetrorelix, a GnRHR1 antagonist, inhibited the
expression of fibrotic genes in vitro and decreased IBDM and hepatic fibrosis in
vivo. Inhibition of miR-200b decreased the expression of fibrosis genes in vitro
in cholangiocyte and HSC lines. Targeting the GnRH/GnRHR1/miR-200b axis may be
key for the management of hepatic fibrosis during the progression of PSC.
PMID- 28502480
TI - Stenotrophomonas maltophilia in a university hospital of traditional Chinese
medicine: molecular epidemiology and antimicrobial resistance.
AB - Stenotrophomona maltophilia has emerged as an important opportunistic pathogen
that is highly antibiotic resistant. Analysis of antibiotic susceptibilities,
drug-resistant gene profiles and molecular typing of S. maltophilia was
undertaken in a university hospital of traditional Chinese medicine in East
China. Resistance to sulphamethoxazole (SXT) was found to be an indicator of
multi-drug resistance. SXT resistance was mediated by sul and dfrA genes in
integrons, especially class 1. Some evidence of clonal dissemination was found,
indicating the occurrence of cross-transmission of antibiotic-resistant strains
within the hospital. This underscores the need for effective control and
prevention measures in hospitals.
PMID- 28502481
TI - Incidence of colonization of central venous catheter and arterial catheter tips
in a paediatric intensive care unit.
PMID- 28502479
TI - Megakaryocytes in Myeloproliferative Neoplasms Have Unique Somatic Mutations.
AB - Myeloproliferative neoplasms (MPNs) are a group of related clonal hemopoietic
stem cell disorders associated with hyperproliferation of myeloid cells. They are
driven by mutations in the hemopoietic stem cell, most notably JAK2V617F, CALR,
and MPL. Clinically, they have the propensity to progress to myelofibrosis and
transform to acute myeloid leukemia. Megakaryocytic hyperplasia with abnormal
features are characteristic, and it is thought that these cells stimulate and
drive fibrotic progression. The biological defects underpinning this remain to be
explained. In this study we examined the megakaryocyte genome in 12 patients with
MPNs to determine whether there are somatic variants and whether there is any
association with marrow fibrosis. We performed targeted next-generation
sequencing for 120 genes associated with myeloid neoplasms on megakaryocytes
isolated from aspirated bone marrow. Ten of the 12 patients had genomic defects
in megakaryocytes that were not present in nonmegakaryocytic hemopoietic marrow
cells from the same patient. The greatest allelic burden was in patients with
increased reticulin deposition. The megakaryocyte-unique mutations were
predominantly in genes that regulate chromatin remodeling, chromosome alignment,
and stability. These findings show that genomic abnormalities are present in
megakaryocytes in MPNs and that these appear to be associated with progression to
bone marrow fibrosis.
PMID- 28502482
TI - Compliance with clothing regulations and traffic flow in the operating room: a
multi-centre study of staff discipline during surgical procedures.
AB - This multi-centre study assessed operating room (OR) staff compliance with
clothing regulations and traffic flow during surgical procedures. Of 1615
surgical attires audited, 56% respected the eight clothing measures. Lack of
compliance was mainly due to inappropriate wearing of jewellery (26%) and head
coverage (25%). In 212 procedures observed, a median of five people
[interquartile range (IQR) 4-6] were present at the time of incision. The median
frequency of entries to/exits from the OR was 10.6/h (IQR 6-29) (range 0-93).
Reasons for entries to/exits from the OR were mainly to obtain materials required
in the OR (N=364, 44.5%). ORs with low compliance with clothing regulations
tended to have higher traffic flows, although the difference was not significant
(P=0.12).
PMID- 28502483
TI - A case report of wound site seeding following cholecystectomy for dysplastic
gallbladder.
AB - Wound site metastasis following cholecystectomy is an uncommon but well
recognised complication following laparoscopic surgery for unsuspected
gallbladder carcinoma. We describe a case of implantation of dysplastic cells
with subsequent malignant transformation at the incision site 3 years post
cholecystectomy for an inflamed gallbladder. Histopathological examination of
this tumour confirmed adenocarcinoma of pancreatobiliary origin, possibly
secondary to gallbladder cells implantation and subsequent carcinomatous change.
Unlike previously reported cases, the present case has two unique features:
Firstly, the histology of the resected gallbladder at the initial operation was
that of a low-grade dysplasia and not carcinoma; and secondly, there was a long
interval between initial surgery and subsequent development of the wound site
tumour. This case highlights that careful handling of the specimen tissue
intraoperatively is paramount as cells implanted in the wound site can survive
and undergo malignant transformation. All new masses occurring along the surgical
wound site should be followed up and investigated to exclude implanted tumours.
PMID- 28502485
TI - Low crowding agent concentration destabilizes against pressure unfolding.
AB - The concentration of macromolecules inside a cell is very high, which can affect
the behavior of the enzymes, and consequently influence vital biological
processes. This is called macromolecular crowding. Since the most important
effect of macromolecular crowding is the excluded volume, we performed pressure
experiments, where the volume (as conjugate parameter to the pressure) is the
crucial factor. We measured the temperature and pressure stability of bovine
serum albumin and lysozyme with various concentrations of crowding agents,
dextran, FicollTM and lysozyme itself. Our most interesting finding is that low
concentration of all the studied crowding agents decreases the pressure stability
of the proteins. We explain this by the reduced hydration volume change in the
crowded environment. Furthermore, we discuss the volumetric parameters and
emphasize the difference between the partial volume of the protein and the volume
it influences, and their relation to the excluded volume which is responsible for
the macromolecular crowding.
PMID- 28502484
TI - Pathogenic Abeta A2V versus protective Abeta A2T mutation: Early stage
aggregation and membrane interaction.
AB - We investigated the effects of punctual A-to-V and A-to-T mutations in the
amyloid precursor protein APP, corresponding to position 2 of Abeta1-42. Those
mutations had opposite effects on the onset and progression of Alzheimer disease,
the former inducing early AD pathology and the latter protecting against the
onset of the disease. We applied Static and Dynamic Light Scattering and Circular
Dichroism, to study the different mutants in the early stages of the aggregation
process, essential for the disease. Comparative results showed that the
aggregation pathways differ in the kinetics and extent of the process, in the
size of the aggregates and in the evolution of the secondary structure, resulting
in fibrils of different morphology, as seen by AFM. Mutated peptides had
comparable toxic effects on N2a cells. Moreover, as assessed by X-ray scattering,
all of them displayed disordering effects on the internal structure of mixed
phospholipids-gangliosides model membranes.
PMID- 28502487
TI - "Mutation-negative" familial hypercholesterolemia-When negative is positive.
PMID- 28502486
TI - JCL roundtable: Cardiovascular disease risk reduction in menopausal women.
AB - Ovarian failure occurs in most women during the late fifth decade or early sixth
decade of life. This causes a number of changes in physiology as estrogen and
progestin concentrations decline. These involve lipoprotein metabolism and the
vasculature. The risk factors for large vessel disease increase, and dysfunction
of the small resistance vessels responds with changes in blood flow to the skin
causing unpleasant symptoms. These and other changes result in visits to the
physician. A reassessment of risk factors and symptoms is needed to develop a new
plan for effective management, both short term and long term.
PMID- 28502488
TI - Lipoprotein-associated phospholipase A2 and its relationship with markers of
subclinical cardiovascular disease: A systematic review.
AB - BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme that
exhibits proinflammatory properties and has been associated with subclinical
cardiovascular disease. OBJECTIVE: The relationship between Lp-PLA2 and
subclinical CVD remains unclear. The goal of this systematic review was to
clarify this relationship. METHODS: An extensive literature search of the MEDLINE
database using Ovid and PubMed was performed. From an initial search of 444
articles, 13 met the inclusion and exclusion criteria and were included in the
review. RESULTS: Of the 13 studies included in the review, 6 examined the
relationship between Lp-PLA2 and coronary artery calcification, of which 3 showed
a significant correlation. Two studies examined the relationship between Lp-PLA2
and endothelial dysfunction, and 1 reported a significant relationship. Five
studies investigated the association of Lp-PLA2 with carotid intima-media
thickness (CIMT), and 3 reported a significant relationship. CONCLUSIONS: This
review shows a variable association between Lp-PLA2 and subclinical disease. This
finding has broad implications for the future of public health and clinical
practice. Future research is needed to clarify what role Lp-PLA2 has in guiding
treatment and if it is involved in plaque instability, which would make it a
useful tool for risk prognostication.
PMID- 28502489
TI - Dietary carbohydrate and fat intakes are differentially associated with lipid
abnormalities in Korean adults.
AB - BACKGROUND: A high prevalence of metabolic syndrome along with increasing rates
of low high-density lipoprotein cholesterol (HDL-C) and elevated triglycerides
(TGs) is shown in Korean adults. Little is known about the associations between
macronutrient intake and lipid abnormalities in the Asian population, whose major
energy source is carbohydrates. OBJECTIVE: We examined the associations of
dietary carbohydrate and fat intakes with lipid abnormalities in Korean adults.
METHODS: A total of 14,301 adults (5715 men and 8586 women) aged >=30 years with
no diagnosis and treatment for diabetes, hypertension, or dyslipidemia were
selected from the 2008 to 2012 Korea National Health and Nutrition Examination
Survey data. From the 24-hour recall data, dietary carbohydrate and fat intakes
were estimated. Multivariate logistic regression was used to estimate odds ratios
for lipid abnormalities, that is, elevated total cholesterol (TC), low HDL-C,
high TC to HDL-C ratio, elevated non-HDL-C, elevated LDL cholesterol (LDL-C), and
elevated TG across quintiles of dietary carbohydrate and fat intakes. RESULTS:
Percentage of energy from carbohydrate was positively associated with elevated TG
and low HDL-C but inversely associated with elevated TC and elevated LDL-C in
both men and women. Energy-adjusted carbohydrate intake also showed a positive
association with low HDL-C. Dietary fat intakes had the opposite associations
with lipid abnormalities than results for carbohydrate. CONCLUSION: High
carbohydrate diet is undesirable with regard to increased TG and reduced HDL-C
despite the benefit for LDL-C. Dietary strategies emphasizing appropriate
macronutrient intakes by the type of lipid abnormalities are recommended for the
prevention of cardiovascular disease in Korean adults.
PMID- 28502491
TI - A novel frameshift mutation in the lipoprotein lipase gene is rescued by
alternative messenger RNA splicing.
AB - BACKGROUND: Type I hyperlipoproteinemia, manifesting as chylomicronemia and
severe hypertriglyceridemia, is a rare autosomal recessive disorder usually
caused by mutations in the lipoprotein lipase gene (LPL). OBJECTIVE: We sought to
determine whether mutations in LPL could explain the clinical indications of a
patient presenting with pancreatitis and hypertriglyceridemia. METHODS: Coding
regions of LPL were amplified by polymerase chain reaction and analyzed by
nucleotide sequencing. The LPL messenger RNA transcript was also analyzed to
investigate whether alternative splicing was occurring. RESULTS: The patient was
homozygous for the mutation c.767_768insTAAATATT in exon 5 of the LPL gene. This
mutation is predicted to result in either a truncated nonfunctional LPL, or
alternatively a new 5' donor splice site may be used, resulting in a full-length
LPL with an in-frame deletion of 3 amino acids. Analysis of messenger RNA from
the patient showed that the new splice site is used in vivo. CONCLUSION:
Homozygosity for a mutation in the LPL gene was consistent with the clinical
findings. Use of the new splice site created by the insertion mutation rescues an
otherwise damaging frameshift mutation, resulting in expression of an almost full
length LPL that is predicted to be partially functional. The patient therefore
has a less severe form of type I hyperlipoproteinemia than would be expected if
she lacked any functional LPL.
PMID- 28502490
TI - Cardiovascular disease prevalence and insulin resistance in the Kyushu-Okinawa
Population Study and the Framingham Offspring Study.
AB - BACKGROUND: Age-adjusted cardiovascular disease (CVD) prevalence rates are
significantly lower in Japan than in the United States. OBJECTIVE: Our aim was to
compare CVD risk in participants in Fukuoka and Framingham. METHODS: We measured
glucose, insulin, high-density lipoprotein cholesterol, low-density lipoprotein
cholesterol (LDL-C), small dense LDL-C, and triglycerides in men and women from
Fukuoka (n = 1108), and age (median, 53 years) and gender-matched subjects from
Framingham (n = 1101). Blood pressure, body mass index, use of medications, and
history of CVD were also assessed. RESULTS: CVD prevalence rates were more than 6
fold higher in Framingham men and women than their Fukuoka counterparts (P <
.001). Median body mass index, LDL-C, insulin levels, and insulin resistance
assessment in Fukuoka men and women were significantly (P < .01) lower than in
Framingham; however, diabetes prevalence in Fukuoka men was significantly (P <
.01) higher than in Framingham men, whereas female rates were similar, as were
levels of systolic blood pressure. High-density lipoprotein cholesterol and
surprisingly small dense LDL-C levels were significantly (P < .001) higher in
Fukuoka than in Framingham. Standard risk factors do not account for the large
differences in CVD prevalence rates between the 2 populations, and population
differences in insulin resistance may explain some of these differences.
CONCLUSIONS: Our data are consistent with the concept that the CVD prevalence
rate in a Japanese population is much lower than those observed in the United
States, and that these differences cannot be explained by standard CVD risk
factors, but may relate to marked population differences in insulin resistance.
PMID- 28502492
TI - Low levels of ApoA1 improve risk prediction of type 2 diabetes mellitus.
AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) has reported to be a major public
health crisis in China. OBJECTIVE: We examined the incidence of new T2DM over 4
years for association of clinical factors and lipids with development of T2DM in
a community-based population. METHODS: We included 923 Chinese subjects who
participated in community-organized health checkout in both 2009 and 2013. Health
history was collected; physical examination was performed; biochemistry, lipids,
and glucose were measured. Of 923, 819 were confirmed without T2DM in 2009 and
included in the analysis. Unadjusted and adjusted logistic regression models were
used to estimate the effects of clinical factors and biomarkers on the risk of
new T2DM. RESULTS: Of 819 subjects without T2DM in 2009, 65 were identified as
T2DM in 2013, 8% over 4 years. These 65 subjects, compared with those 754 without
new T2DM, were older, more likely to be male and smokers. They had higher body
mass index (BMI), fasting glucose, blood pressure and triglycerides, and lower
levels of high-density lipoprotein-cholesterol and apolipoprotein A1 (ApoA1).
Multivariate logistic regression identified larger BMI (odds ratio [OR] = 1.7;
95% confidence interval [CI], 1.22-2.39, P = .002), higher fasting glucose levels
(OR = 4.2, 95% CI, 2.90-6.19, P < .001), and low levels of ApoA1 (OR = 0.51, 95%
CI 0.33-0.76, P = .002) were independently associated with new T2DM. Furthermore,
receiver operating characteristics curves for multivariate models for new T2DM
showed that area under the curve improved from 0.87 to 0.89 when adding ApoA1 to
the Framingham Diabetes Risk Scoring Model and from 0.85 to 0.89 when adding
ApoA1 to a 4-variable (age, BMI, glucose, and triglycerides) Chinese model.
CONCLUSIONS: There is a high incidence of new T2DM at 8% over 4 years among
Chinese. Larger BMI, higher glucose levels, and lower levels of ApoA1 are
significantly and independently associated with new T2DM. Lower ApoA1 improves
the risk prediction of new type 2 diabetes when it was added to the existing risk
models.
PMID- 28502493
TI - The effect of maximal vs submaximal exertion on postprandial lipid levels in
individuals with and without coronary heart disease.
AB - BACKGROUND: Decisions about fat consumption and levels of physical activity are
among the everyday choices we make in life and risk of coronary heart disease
(CHD) can be affected by those choices. OBJECTIVE: The purpose of this study was
to investigate the influence of a standard fat load combined with physical
exertion of different intensities on the plasma lipid profile of CHD patients and
CHD-free individuals. METHODS: This study looked at the influence of different
intensities of physical exercise on postprandial lipid metabolism in 20 healthy
men and 36 men with diagnosis of CHD. Venous blood samples were obtained after
overnight fasting, 3 hours after standard fat load (before the physical load),
and immediately after maximal or submaximal physical exercise on bicycle
ergometer. RESULTS: After fat load total cholesterol (TC) concentration did not
change in either group. However, after the addition of maximal exercise, TC,
triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and
apolipoprotein (Apo) B increased significantly (P < .01) in both groups. After
fat load and maximal exercise, there was no change in high-density lipoprotein
cholesterol (HDL-C) in healthy men, but in men with CHD, HDL-C fell significantly
(P < .01); and Apo AI rose in healthy men (P < .01) but dropped significantly (P
< .01) in men with CHD. Submaximal physical exercise (60% of max VO2 load for 40
minutes) after fat load decreased TG level in CHD patients (P < .01) and improved
other lipid parameters in both groups significantly (?LDL-C, ?HDL-C, ?Apo AI,
?Apo B, P < .01). We observed a worsening of physical work capacity in men with
CHD (significant reduction of duration and total amount of work performed,
maximal VO2, oxygen pulse), during maximal stress test performed 3 hours after
fat load. There was a doubling of the number of abnormal stress test results (P <
.01). Healthy persons showed an increase in respiratory parameters (ventilation,
CO2 production, maximal VO2, and oxygen pulse), but no significant change was
found in work capacity. Thus, maximal physical exercise produced atherogenic
blood lipid changes (increased TC, increased LDL-C, increased TG, increased Apo
B, P < .01) in men with CHD and in healthy men; however, individuals with CHD
also demonstrated a significant decrease in HDL-C and Apo AI (P < .01). In
contrast, the submaximal physical load improved postprandial lipid changes in
both healthy men and men with CHD. CONCLUSIONS: This study demonstrates that
moderate exercise is beneficial in improving postprandial lipid abnormalities in
both CHD and CHD-free subjects after fatty meal preload. In addition, maximal
exercise demonstrated evidence of increase of lipid abnormalities in both CHD and
CHD-free individuals under similar conditions of fatty meal preload.
PMID- 28502494
TI - Association of fasting triglyceride concentration and postprandial triglyceride
response with the carotid intima-media thickness in the middle aged: The
Netherlands Epidemiology of Obesity study.
AB - BACKGROUND: People are in a postprandial state for the majority of the day,
postprandial triglyceride (TG) response may be more important in the etiology of
atherosclerosis than fasting TGs. OBJECTIVE: The objective of the study was to
investigate the associations of fasting TG concentration (TGc) and postprandial
TG response after a meal challenge with subclinical atherosclerosis, measured by
intima-media thickness (IMT) in a middle-aged population. METHODS: A total of
5574 participants (57% women) with a mean (standard deviation [SD]) age of 56 (6)
years were included in this cross-sectional analysis of baseline measurements of
The Netherlands Epidemiology of Obesity study. Serum TGc was measured fasting and
30 and 150 minutes after a liquid mixed meal, and the incremental area under the
curve (TGiAUC) was calculated. With linear regression analyses, we calculated the
differences in IMT with 95% confidence intervals, adjusted for confounding
factors, and additionally for TGc or TGiAUC. RESULTS: Per SD of TGc (0.82
mmol/L), IMT was 8.5 MUm (2.1, 14.9) greater after adjustment for TGiAUC and
confounding factors. Per SD of TGiAUC (24.0 mmol/L * min), the difference in IMT
was -1.7 MUm (-8.5, 5.0) after adjustment for fasting TG and confounding factors.
CONCLUSIONS: The association between TG response after a mixed meal and IMT
disappeared after adjusting for TGc. The association between fasting TG
concentration and IMT persisted after adjustment for postprandial TG response.
These findings imply that it is not useful to perform a meal challenge in
cardiovascular risk stratification. Our results support use of fasting TGc
instead of postprandial TG responses for cardiovascular risk stratification in
clinical practice.
PMID- 28502495
TI - Detection of common sequence variations of familial hypercholesterolemia in
Taiwan using DNA mass spectrometry.
AB - BACKGROUND: Familial hypercholesterolemia (FH) is a heterogeneous autosomal
dominant disease. The genetic heterogeneity of FH requires low-cost, high
throughput, and rapid mutation detection technology to efficiently integrate
genetic screening into clinical practice. OBJECTIVES: The aims of the study were
to customize the MassARRAY assay to (1) establish an FH mutation assay panel,
comprising known point mutations located on FH-causing genes and (2) test the
feasibility of the assay for screening FH patients residing in Taiwan who fit the
clinical criteria of FH diagnosis. METHODS: We designed a custom Agena iPLEX
assay to detect 68 point mutations on FH-causing genes. First, the assay
performance was verified by analyzing 180 previously sequenced subjects (120 with
point mutations and 60 healthy controls), with the results being compared with
those of Sanger DNA sequencing. Second, a blind study was carried out on 185 FH
probands (44 definite FH and 141 probable/possible FH). RESULTS: In the first
part of this study, only 1 discrepancy was found between the Agena iPLEX and
Sanger sequencing genotyping results. In the blind study, a total of 62 probands
with mutations were identified by both techniques. Five mutations were detected
by Sanger sequencing assay only. The detection sensitivity and specificity rates
of Agena iPLEX were 92.5% and 100%, respectively, in the blind study. The hands
on time for the Agena iPLEX assay was around 1 day. CONCLUSIONS: The custom
designed Agena iPLEX assay has high specificity and sensitivity for FH genetic
screening. Considering its low cost, rapidity, and flexibility, the assay has
great potential to be incorporated into FH screening in Taiwan.
PMID- 28502497
TI - The 9p21.3 locus and cardiovascular risk in familial hypercholesterolemia.
AB - BACKGROUND: Carrying a risk variant in the 9p21.3 locus represents one of the
strongest genetic risk factors for atherosclerotic cardiovascular disease (ASCVD)
in the general population. However, the effect of these polymorphisms in patients
with familial hypercholesterolemia (FH) has never been studied. OBJECTIVE: The
objective of this study was to investigate the association between the sentinel
9p21.3 single nucleotide polymorphisms (SNP) rs1333047 and ASCVD susceptibility
in FH subjects. METHODS: A total of 20,434 Caucasian patients with dyslipidemia
were screened, of which 725 FH were included in this study. The risk allele (T)
of the rs1333047 SNP has previously been shown to confer increased ASCVD risk
compared with the control allele (A). RESULTS: In a model adjusted for
traditional cardiovascular risk factors, carrying the risk allele was associated
with a 42% increased ASCVD susceptibility per allele, according to an additive
model (odds ratio = 1.42; 95% confidence interval, 1.05-1.91; P = .02). On
average, 0.53 cardiovascular event was observed in AA carriers, compared with
0.83 in the TT group (P = .02). The mean age of first ASCVD event was similar
among the 3 variants. CONCLUSION: The 9p21.3 SNP rs1333047 SNP was associated
with increased ASCVD in FH subjects. Genetic screening for this SNP could allow
to identify very high risk FH patients, which could benefit from more aggressive
ASCVD prevention.
PMID- 28502496
TI - Minimal food effect for eicosapentaenoic acid and docosahexaenoic acid
bioavailability from omega-3-acid ethyl esters with an Advanced Lipid
TechnologiesTM (ALT(r))-based formulation.
AB - BACKGROUND: The absorption of eicosapentaenoic acid (EPA; 20:5n-3) and
docosahexaenoic acid (DHA; 22:6n-3) omega-3-acid ethyl esters (EEs) is influenced
by food. There is a need for a formulation of EE that is less impacted by food
effect. SC401 is a novel Advanced Lipid Technologies-based formulation of EPA-EE
and DHA-EE. In the presence of an aqueous medium, Advanced Lipid Technologies
forms stable micelles in situ independent of bile salt secretion. This effect is
hypothesized to improve EPA-EE and DHA-EE bioavailability while it helps mitigate
the food effect associated with their consumption. OBJECTIVE: The aim of the
article was to assess the effect of food on the bioavailability of DHA and EPA
after a single oral dose of 1530 mg omega-3 fatty acids EE (SC401) in 24 healthy
subjects under fasted and low-fat (9% of total calories from fat) and high-fat
(50% of total calories from fat) meal conditions. METHODS: This was a randomized,
open-label, single-dose, 3-period, 3-way crossover study. Blood samples for
pharmacokinetic analyses were taken at predose and at 0.5, 1, 2, 3, 3.5, 4, 4.5,
5, 5.5, 6, 6.5, 7, 8, 10, 12 and 24 hours postdose. To assess the safety of the
intervention, active monitoring of adverse events, physical examinations, vital
signs, clinical laboratory assessments (chemistry, hematology, and urinalysis),
and 12-lead electrocardiograms were conducted. RESULTS: SC401 showed high
bioavailability of both EPA and DHA in fasted, low-fat meal, and high-fat meal
conditions. No differences were found in SC401 DHA AUC0-t (t = 24 hours) among
the 3 conditions (91.69% high-fat/fasted, 97.12% low-fat/fasted, and 105.92% low
fat/high-fat; P > .05 in all cases). In contrast, SC401 EPA AUC0-t was affected
by food intake (179.06% high-fat/fasted, P < .0001; 150.05% low-fat/fasted, P <
.0001) and the amount of fat taken with SC401 (83.80% low-fat/high-fat; P =
.0009). SC401 was safe and well tolerated. CONCLUSIONS: A single dose of SC401
resulted in high levels of EPA and DHA total lipids in plasma in fasting and fed
conditions. SC401 overcame the food effect for DHA and partially ameliorated it
for EPA. SC401 represents a convenient option for treatment of severe
hypertriglyceridemia, especially for patients under a restricted intake of
dietary fat.
PMID- 28502499
TI - Effects of statin therapy on cerebrovascular and renal outcomes in patients with
predialysis advanced chronic kidney disease and dyslipidemia.
AB - BACKGROUND: Treatment with statin may be beneficial for patients with chronic
kidney disease (CKD). However, the debate over the clinical importance of statin
in patients with predialysis advanced CKD remains unresolved. OBJECTIVES: The
objective of the article was to evaluate the effect of statin on mortality,
cerebrovascular, and renal outcomes in patients with predialysis advanced CKD and
dyslipidemia. METHODS: Data on predialysis advanced CKD patients were retrieved
from the National Health Insurance Research Database based on the guidelines for
prescribing regular erythropoietin-stimulating agent in CKD patients. Patients
with dyslipidemia were further selected and divided into 2 groups by their statin
use after the prescribed erythropoietin-stimulating agent. All-cause mortality
and cerebrovascular and renal outcomes were analyzed after propensity score
matching. RESULTS: There were 2016 and 14,412 patients in the statin and
nonstatin groups. Their average follow-up periods were 3.7 and 3.0 years,
respectively. After 1:2 propensity score matching, the annual all-cause mortality
rate was higher in the nonstatin than in the statin group (143.99 vs 109.50 per
1000 person-years; P < .001; hazard ratio: 0.73; 95% confidence interval: 0.68
080). The annual risk of ischemic stroke (P = .186) and intracranial hemorrhage
(P = .322) were not significantly different between the 2 groups. The nonstatin
group had a higher risk of dialysis than the statin group (1269.45 vs 1095.00 per
1000 person-years; P = .002). Adverse events were not significant between the 2
groups. CONCLUSIONS: Statins may reduce the all-cause mortality and reduced the
risk of dialysis in patients with predialysis advanced CKD and dyslipidemia.
However, statins have no impact on ischemic-hemorrhage stroke.
PMID- 28502498
TI - Mature proprotein convertase subtilisin/kexin type 9, coronary atheroma burden,
and vessel remodeling in heterozygous familial hypercholesterolemia.
AB - BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9), an important
contributor to low-density lipoprotein metabolism in heterozygous familial
hypercholesterolemia (HeFH), exhibits direct proatherogenic effects. PCSK9
circulates as mature and furin-cleaved forms, which differ in its biological
activity. However, it remains to be elucidated whether each PCSK9 subtype has
different atherogenic properties. OBJECTIVE: To investigate the association of
each PCSK9 subtype with coronary atherosclerosis in HeFH. METHODS: About 204
nonculprit segments in 138 HeFH subjects with coronary artery disease were
evaluated by using intravascular ultrasound. Mature, furin-cleaved PCSK9 and
total concentration of PCSK9 subtypes were measured by using enzyme-linked
immunosorbent assay (BML Inc., Tokyo, Japan). The relationship of these PCSK9
values with intravascular ultrasound measures was investigated. RESULTS: Mature
PCSK9 level was positively associated with percent atheroma volume (PAV: r =
0.78, P = .003). Despite extensive atheroma under a higher mature PCSK9 level,
vessel volume did not change across any mature PCSK9 levels (r = 0.05, P = .78).
These responses resulted in smaller lumen volume, which was negatively correlated
to mature PCSK9 level (r = 0.65, P = .009). By contrast, there were no
significant relationships of PAV with furin-cleaved (r = 0.12, P = .45) and total
PCSK9 (r = 0.37, P = .25) levels. On multivariate analysis, mature PCSK9 level
independently contributed to PAV (odds ratio: 1.45, 95% confidence interval: 1.11
1.67, P = .01). Even in subjects with low-density lipoprotein cholesterol level
<2.6 mmol/L, greater PAV was still observed in association with an elevated
mature PCSK9 level (P = .003). CONCLUSIONS: Mature PCSK9 associated with atheroma
volume and impaired vessel remodeling in HeFH patients with coronary artery
disease. These findings suggest the potential role of mature PCSK9 in propagation
of coronary atherosclerosis in HeFH.
PMID- 28502500
TI - The association between dietary cholesterol intake and subclinical
atherosclerosis in Korean adults: The Kangbuk Samsung Health Study.
AB - BACKGROUND: The Scientific Report of the Dietary Guidelines Advisory Committee
(2015) concluded that restriction of dietary cholesterol is unnecessary in most
adults for the prevention of cardiovascular disease. OBJECTIVE: We aimed to
assess the risk for subclinical atherosclerosis according to coronary artery
calcium score (CACS), based on dietary cholesterol intake in apparently healthy
Korean adults. METHODS: This was a cross-sectional study performed in 30,068
participants (mean age 40.8 years; 84.5% men) in a health screening program in
Korea. The data were collected from 2001 to 2013 and analyzed in 2015. Total
energy intake and dietary cholesterol intake were assessed with a food frequency
questionnaire. The participants were stratified according to quartile of dietary
cholesterol intake. CACS was measured by multi-detector computed tomography.
Lipid profiles were measured, and the participants were divided into 6 groups
according to low-density lipoprotein cholesterol (LDL-C) level: <70, 70 to 99,
100 to 129, 130 to 159, 160 to 189, and >=190 mg/dL. RESULTS: The presence of
coronary artery calcification was defined as CACS>0. Dietary cholesterol intake
did not correlate with mean value of serum LDL-C level. For both genders, the
odds ratio for coronary artery calcification was not significantly greater with
greater amounts of dietary cholesterol (as assessed by quartile). The risk for
coronary artery calcification was not higher in subjects with LDL-C 70-129 mg/dL
compared with those with LDL-C < 70 mg/dL; however, the risk was significantly
greater in subjects with LDL-C >= 130 mg/dL compared with those with LDL-C < 70
mg/dL. CONCLUSIONS: Dietary cholesterol intake did not have an association with
LDL-C level or with risk for coronary artery calcification in apparently healthy
Korean adults. The results have to be translated with consideration of limitation
of population-based studies.
PMID- 28502501
TI - Apolipoprotein B vs non-high-density lipoprotein cholesterol: Association with
endothelial hemostatic markers and carotid intima-media thickness.
AB - BACKGROUND: Both apolipoprotein B (apoB) and non-high-density lipoprotein
cholesterol (non-HDL-C) are accepted as alternative risk factors or targets for
lipid-lowering therapy, which correlate more strongly with cardiovascular events
than low-density lipoprotein cholesterol. OBJECTIVE: The aim of this cross
sectional study was to evaluate the differences in plasma levels of plasminogen
activator inhibitor-1 (PAI-1) and of von Willebrand factor (vWF) as endothelial
hemostatic markers and carotid intima-media thickness (C-IMT) as a morphologic
marker for atherosclerotic vascular disease among dyslipidemic individuals with
apoB levels higher, estimated or lower based on regression equation of apoB vs
non-HDL-C. METHODS: A total of 594 dyslipidemic subjects without atherosclerotic
manifestation were divided into 3 groups (according to tertiles of apoB levels
above, within, and below the line of identity): H-apoB (n = 200), E-apoB (n =
194), and L-apoB (n = 200). PAI-1, vWF, C-IMT and lipids, anthropometric
parameters, markers of insulin resistance, and inflammation were measured.
Differences in variables between groups were analyzed using analysis of variance.
RESULTS: There was a strong association between apoB and non-HDL-C. The
correlations of apoB and of non-HDL-C with markers of endothelial damage and C
IMT were very similar. Despite these facts, individuals with higher apoB levels
had significantly higher levels of PAI-1 compared with individuals with estimated
(P < .05) or lower apoB (P < .001). There were no significant differences in vWF,
C-IMT, markers of insulin resistance, obesity, and inflammation. CONCLUSION:
Individuals with apoB higher than predicted by non-HDL-C had significantly higher
levels of PAI-1, which may contribute to the increased risk of future
atherothrombotic events.
PMID- 28502502
TI - Dapagliflozin in patients with type II diabetes mellitus, with and without
elevated triglyceride and reduced high-density lipoprotein cholesterol levels.
AB - BACKGROUND: Dapagliflozin is a selective sodium-glucose cotransporter 2 inhibitor
that improves glycemic control in patients with type II diabetes mellitus (T2DM)
by reducing renal glucose reabsorption. OBJECTIVE: The aim was to evaluate the
lipid effects of dapagliflozin 10 mg or placebo in patients with T2DM
with/without baseline elevated triglyceride and reduced high-density lipoprotein
(HDL) cholesterol levels. METHODS: This was a post hoc analysis of 10 phase 3,
placebo-controlled studies of dapagliflozin 10 mg (N = 2237) or placebo (N =
2164) administered for 24 weeks in patients with T2DM. Patients with elevated
triglyceride (>=150 mg/dL [1.69 mmol/L]) and reduced HDL cholesterol levels (<40
mg/dL [1.04 mmol/L] in men; <50 mg/dL [1.29 mmol/L] in women) were included
(group A). The reference group (group B) included patients who did not meet the
defined lipid criteria. RESULTS: The effects of dapagliflozin on fasting lipid
profiles were generally similar in the 2 lipid groups (ie, groups A and B) and,
compared with placebo, were associated with minor increases in non-HDL
cholesterol, low-density lipoprotein, and HDL cholesterol levels. The effects on
triglyceride levels were inconsistent. The incidence of adverse events
(AEs)/serious AEs, and AEs of genital infection, urinary tract infection, volume
reduction, renal function, and hypoglycemia were similar in the 2 lipid groups.
CONCLUSION: Patients with T2DM treated with dapagliflozin experienced minor
changes in lipid levels; the changes were generally similar in the 2 lipid
groups. The clinical significance of these changes in lipids is unclear,
especially in view of the positive effects of dapagliflozin on other
cardiovascular disease risk factors.
PMID- 28502503
TI - The effects of vitamin D and omega-3 fatty acid co-supplementation on glycemic
control and lipid concentrations in patients with gestational diabetes.
AB - OBJECTIVE: This study was performed to evaluate the effects of vitamin D and
omega-3 fatty acids co-supplementation on glucose metabolism and lipid
concentrations in gestational diabetes (GDM) patients. METHODS: This randomized
double-blind placebo-controlled clinical trial was done among 140 GDM patients.
Participants were randomly divided into 4 groups to receive: (1) 1000 mg omega-3
fatty acids containing 360 mg eicosapentaenoic acid and 240 mg docosahexaenoic
acid (DHA) twice a day + vitamin D placebo (n = 35); (2) 50,000 IU vitamin D
every 2 weeks + omega-3 fatty acids placebo (n = 35); (3) 50,000 IU vitamin D
every 2 weeks + 1000 mg omega-3 fatty acids twice a day (n = 35), and (4) vitamin
D placebo + omega-3 fatty acids placebo (n = 35) for 6 weeks. RESULTS: After 6
weeks of intervention, patients who received combined vitamin D and omega-3 fatty
acids supplements compared with vitamin D, omega-3 fatty acids, and placebo had
significantly decreased fasting plasma glucose (-7.3 +/- 7.8, -6.9 +/- 6.6, -4.0
+/- 2.5, and +1.0 +/- 11.4 mg/dL, respectively, P < .001), serum insulin levels (
1.9 +/- 1.9, -1.3 +/- 6.3, -0.4 +/- 6.3, and +2.6 +/- 6.5 MUIU/mL, respectively,
P = .005), homeostatic model of assessment for insulin resistance (-0.7 +/- 0.6,
0.5 +/- 1.4, -0.2 +/- 1.5, and +0.6 +/- 1.5, respectively, P < .001) and
increased quantitative insulin sensitivity check index (+0.01 +/- 0.01, +0.008 +/
0.02, +0.002 +/- 0.02, and -0.005 +/- 0.02, respectively, P = .001). In
addition, changes in serum triglycerides (-8.2 +/- 41.0, +7.6 +/- 31.5, +3.6 +/-
29.9, and +20.1 +/- 29.6 mg/dL, respectively, P = .006) and very low-density
lipoprotein cholesterol (-1.6 +/- 8.2, +1.5 +/- 6.3, +0.8 +/- 6.0, and +4.0 +/-
5.9 mg/dL, respectively, P = .006) in the vitamin D plus omega-3 fatty acids
group were significantly different from the changes in these indicators in the
vitamin D, omega-3 fatty acids, and placebo groups. CONCLUSION: Overall, vitamin
D and omega-3 fatty acids co-supplementation for 6 weeks among GDM patients had
beneficial effects on fasting plasma glucose, serum insulin levels, homeostatic
model of assessment for insulin resistance, quantitative insulin sensitivity
check index, serum triglycerides, and very low-density lipoprotein cholesterol
levels.
PMID- 28502504
TI - High-density lipoproteins and adrenal steroidogenesis: A population-based study.
AB - BACKGROUND: Cholesterol trafficked within plasma lipoproteins, in particular high
density lipoproteins (HDL), may represent an important source of cholesterol that
is required for adrenal steroidogenesis. Based on a urinary gas chromatography
method, compromised adrenal function has been suggested in men but not in women
with (genetically determined) low plasma HDL-cholesterol (HDL-C). OBJECTIVE: The
objective of the article was to examine the extent to which glucocorticoid
production relates to HDL-C in a population-based cohort. METHODS: A total of 240
subjects (120 men and 120 women, aged 20-79 years) without relevant comorbidities
were recruited from the general population. Glucocorticoid metabolites were
measured by gas chromatography with tandem mass spectrometric detection in 24
hour urine collections to estimate total glucocorticoid production (TGP). Fasting
plasma (apo)lipoproteins were assayed by routine methods. RESULTS: TGP was not
decreased but tended to be increased in subjects with low HDL-C (NCEP-ATPIII
criteria; P = .094). In univariate analysis, TPG was correlated inversely with
HDL-C (r = -0.353, P < .001) and apoA-I (r = -0.263, P = .01). Multivariable
linear regression analysis demonstrated that TGP was still inversely related to
HDL-C (beta = -0.145, P = .019) or alternatively to low HDL-C (beta = -0.129, P =
.013) taking age, sex, current smoking, and other metabolic syndrome components
into account. CONCLUSION: In this population-based study, urinary glucocorticoid
metabolite excretion was inversely associated with HDL-C. We found no evidence
for an attenuated adrenal function in men and women with low HDL-C.
PMID- 28502506
TI - Attitudes and actions: A survey to assess statin use among Finnish patients with
increased risk for cardiovascular events.
AB - BACKGROUND: Statins are the first-line treatment for lowering serum cholesterol
and preventing coronary artery disease (CAD). Patients who fail to comply with
the prescribed statin treatment face a markedly increased risk for cardiovascular
events. OBJECTIVE: The aim of the article was to study the subjective factors,
which modulate persistence with and adherence to statin therapy among Finnish
patients at high risk for cardiovascular events. METHODS: A total of 1022 Finnish
adults diagnosed with CAD, diabetes, hypertension, or severe hereditary
dyslipidemia completed an electronic questionnaire survey during a visit in 1 of
the 84 community pharmacies participating in the study. RESULTS: Thirty-four
percent of the survey respondents were diagnosed with CAD or severe hereditary
dyslipidemia and 82% were current or former statin users. Prevalence of
nonpersistence with statin therapy was 15% among CAD patients and 17% among
respondents without the diagnosis. Most of the nonpersistent statin users had
discontinued the medication without consultation of a physician. None of the
studied sociodemographic background factors were associated with persistence with
statin therapy. Instead, experienced adverse effects, fear of adverse effects,
perceived lack of need, and difficulties in use of a statin emerged as powerful
predictors of nonpersistence. Awareness of treatment goals was low, and
strikingly, public discussion about adverse effects of statins had induced nearly
every third discontinuation of statin treatment. CONCLUSION: Several subjective,
potentially modifiable reasons for nonpersistence were identified from the
patient perspective. Improved utilization of patient-centered approaches in
pharmacologic management of cardiovascular risks is necessary to improve
adherence, and ultimately, treatment outcomes.
PMID- 28502505
TI - Lysosomal acid lipase deficiency: A hidden disease among cohorts of familial
hypercholesterolemia?
AB - BACKGROUND: Lysosomal acid lipase deficiency (LALD) is an autosomal recessive
disorder and an unrecognized cause of dyslipidemia. Patients usually present with
dyslipidemia and altered liver function and mutations in LIPA gene are the
underlying cause of LALD. OBJECTIVE: The aim of this study was to investigate
LALD in individuals with severe dyslipidemia and/or liver steatosis. METHODS:
Coding, splice regions, and promoter region of LIPA were sequenced by Sanger
sequencing in a cohort of mutation-negative familial hypercholesterolemia (FH)
patients (n = 492) and in a population sample comprising individuals with several
types of dyslipidemia and/or liver steatosis (n = 258). RESULTS: This study led
to the identification of LALD in 4 children referred to the Portuguese FH Study,
all with a clinical diagnosis of FH. Mild liver dysfunction was present at the
age of FH diagnosis; however, a diagnosis of LALD was not considered. No adults
at the time of referral have been identified with LALD. CONCLUSION: LALD is a
life-threatening disorder, and early identification is crucial for the
implementation of specific treatment to avoid premature mortality. FH cohorts
should be investigated to identify possible LALD patients, who will need
appropriate treatment. These results highlight the importance of correctly
identifying the etiology of the dyslipidemia.
PMID- 28502507
TI - Impact of bariatric surgery on apolipoprotein C-III levels and lipoprotein
distribution in obese human subjects.
AB - BACKGROUND: Elevated apolipoprotein C-III (apoC-III) has been postulated to
contribute to the atherogenic dyslipidemia seen in obesity and insulin-resistant
states, mainly by impairing plasma triglyceride-rich lipoprotein (TRL)
metabolism. Bariatric surgery is associated with improvements of several obesity
associated metabolic abnormalities, including a reduction in plasma triglycerides
(TGs) and an increase in plasma high-density lipoprotein cholesterol (HDL-C).
OBJECTIVES: We investigated the specific effect of bariatric surgery on apoC-III
concentrations in plasma, non-HDL, and HDL fractions in relation to lipid profile
parameters evolution. METHODS: A total of 132 obese subjects undergoing bariatric
surgery, gastric bypass (n = 61) or sleeve gastrectomy (n = 71), were studied 1
month before surgery and 6 and 12 months after surgery. RESULTS: Plasma apoC-III,
non-HDL-apoC-III, and HDL-apoC-III concentrations were markedly reduced after
surgery and strongly associated with reduction in plasma TG. This decrease was
accompanied by a redistribution of apoC-III from TRL to HDL fractions. In
multivariate analysis, plasma apoC-III was the strongest predictor of TG
reduction after surgery, and the increase of HDL-C was positively associated with
plasma adiponectin and negatively with body mass index. CONCLUSION: Marked
reduction of apoC-III and changes in its distribution between TRL and HDL
consistent with a better lipid profile are achieved in obese patients after
bariatric surgery. These apoC-III beneficial modifications may have implications
in dyslipidemia improvement and contribute to cardiovascular risk reduction after
surgery.
PMID- 28502508
TI - Plasma lipoprotein(a) levels in patients with homozygous autosomal dominant
hypercholesterolemia.
AB - BACKGROUND: Patients with autosomal dominant hypercholesterolemia (ADH), caused
by mutations in either low-density lipoprotein receptor (LDLR), apolipoprotein B
(APOB), or proprotein convertase subtilisin-kexin type 9 (PCSK9) are
characterized by high low-density lipoprotein cholesterol levels and in some
studies also high lipoprotein(a) (Lp(a)) levels were observed. The question
remains whether this effect on Lp(a) levels is gene-dose-dependent in individuals
with either 0, 1, or 2 LDLR or APOB mutations. OBJECTIVE: We set out to study
whether Lp(a) levels differ among bi-allelic ADH mutation carriers, and their
relatives, in the Netherlands. METHODS: Bi-allelic ADH mutation carriers were
identified in the database of the national referral laboratory for DNA
diagnostics of inherited dyslipidemias. Family members were invited by the index
cases to participate. Clinical parameters and Lp(a) levels were measured in bi
allelic ADH mutation carriers and their heterozygous and unaffected relatives.
RESULTS: We included a total of 119 individuals; 34 bi-allelic ADH mutation
carriers (20 homozygous/compound heterozygous LDLR mutation carriers (HoFH), 2
homozygous APOB mutation carriers (HoFDB), and 12 double heterozygotes for an
LDLR and APOB mutation), 63 mono-allelic ADH mutation carriers (50 heterozygous
LDLR [HeFH], 13 heterozygous APOB [HeFDB] mutation carriers), and 22 unaffected
family members. Median Lp(a) levels in unaffected relatives, HeFH, and HoFH
patients were 19.9 (11.1-41.5), 24.4 (5.9-70.6), and 47.3 (14.9-111.7) mg/dL,
respectively (P = .150 for gene-dose dependency). Median Lp(a) levels in HeFDB
and HoFDB patients were 50.3 (18.7-120.9) and 205.5 (no interquartile range
calculated), respectively (P = .012 for gene-dose-dependency). Double
heterozygous carriers of LDLR and APOB mutations had median Lp(a) levels of 27.0
(23.5-45.0), which did not significantly differ from HoFH and HoFDB patients (P =
.730 and .340, respectively). CONCLUSION: A (trend toward) increased plasma Lp(a)
levels in homozygous ADH patients compared with both heterozygous ADH and
unaffected relatives was observed. Whether increased Lp(a) levels in homozygous
ADH patients add to the increased cardiovascular disease risk and whether this
risk can be reduced by therapies that lower both low-density lipoprotein
cholesterol and Lp(a) levels remains to be elucidated.
PMID- 28502509
TI - The heterozygous N291S mutation in the lipoprotein lipase gene impairs whole-body
insulin sensitivity and affects a distinct set of plasma metabolites in humans.
AB - BACKGROUND: Mutations in the lipoprotein lipase gene causing decreased
lipoprotein lipase activity are associated with surrogate markers of insulin
resistance and the metabolic syndrome in humans. OBJECTIVE: We investigated the
hypothesis that a heterozygous lipoprotein lipase mutation (N291S) induces whole
body insulin resistance and alterations in the plasma metabolome. METHODS: In 6
carriers of a heterozygous lipoprotein lipase mutation (N291S) and 11 age-matched
and weight-matched healthy controls, we examined insulin sensitivity and
substrate metabolism by euglycemic-hyperinsulinemic clamps combined with indirect
calorimetry. Plasma samples were taken before and after the clamp (4 hours of
physiological hyperinsulinemia), and metabolites were measured enzymatically or
by gas chromatography-mass spectrometry. RESULTS: Compared with healthy controls,
heterozygous carriers of a defective lipoprotein lipase allele had elevated
fasting plasma levels triglycerides (P < .006), and markedly impaired insulin
stimulated glucose disposal rates (P < .024) and nonoxidative glucose metabolism
(P < .015). Plasma metabolite profiling demonstrated lower circulating levels of
pyruvic acid and alpha-tocopherol in the N291S carriers than in controls both
before and after stimulation with insulin (all >1.5-fold change and P < .05).
CONCLUSION: Heterozygous carriers with a defective lipoprotein lipase allele are
less insulin sensitive and have increased plasma levels of nonesterified fatty
acids and triglycerides. The heterozygous N291S carriers also have a distinct
plasma metabolomic signature, which may serve as a diagnostic tool for deficient
lipoprotein lipase activity and as a marker of lipid-induced insulin resistance.
PMID- 28502510
TI - Preliminary spectrum of genetic variants in familial hypercholesterolemia in
Argentina.
AB - BACKGROUND: Familial hypercholesterolemia (FH) is a genetic disorder
characterized by elevated low-density lipoprotein cholesterol and early
cardiovascular disease. As cardiovascular disease is a leading cause of mortality
in Argentina, early identification of patients with FH is of great public health
importance. OBJECTIVE: The aim of our study was to identify families with FH and
to approximate to the characterization of the genetic spectrum mutations of FH in
Argentina. METHODS: Thirty-three not related index cases were selected with
clinical diagnosis of FH. Genetic analysis was performed by sequencing, multiplex
ligation-dependent probe amplification, and bioinformatics tools. RESULTS: Twenty
genetic variants were identified among 24 cases (73%), 95% on the low-density
lipoprotein receptor gene. The only variant on APOB was the R3527Q. Four were
novel variants: c.-135C>A, c.170A>C p.(Asp57Ala), c.684G>C p.(Glu228Asp), and
c.1895A>T p.(Asn632Ile); the bioinformatics' analysis revealed clear
destabilizing effects for 2 of them. The exon 14 presented the highest number of
variants (32%). Four variants were observed in more than 1 case and the c.2043C>A
p.(Cys681*) was carried by 18% of index cases. Two true homozygotes, 3 compound
heterozygotes, and 1 double heterozygote were identified. CONCLUSION: This study
characterizes for the first time in Argentina genetic variants associated with FH
and suggest that the allelic heterogeneity of the FH in the country could have 1
relative common low-density lipoprotein receptor mutation. This knowledge is
important for the genotype-phenotype correlation and for optimizing both
cholesterol-lowering therapies and mutational analysis protocols. In addition,
these data contribute to the understanding of the molecular basis of FH in
Argentina.
PMID- 28502511
TI - Functional analysis of new 3' untranslated regions genetic variants in genes
associated with genetic hypercholesterolemias.
AB - BACKGROUND: Familial hypercholesterolemia (FH) is the best-described autosomal
dominant genetic hypercholesterolemia (GH). Mutations in candidate genes can
explain a high proportion of FH cases, but for many, no causative mutations are
detected (designed non-FG-GH), suggesting the existence of additional genetic
variants associated with the disease. OBJECTIVE: We aimed to identify new single
nucleotide variants (SNVs) located at the 3' untranslated regions (3'UTRs) of the
low-density lipoprotein receptor, low-density lipoprotein receptor-related
protein-associated protein 1, ATP-binding cassette sub-family G member 5, and
sterol regulatory element-binding protein 2 genes in non-FH-GH individuals and
investigated whether the association of these SNVs with non-FH-GH could be
explained by changes in the affinity of regulatory microRNAs (miRNA) targeting
the sequences modified by the SNVs. METHODS: The study includes probands with non
FH-GH attending 2 lipid clinics in Spain. We performed functional analyses of
selected variants using a luciferase reporter system. Through in silico target
prediction tools, we identified miRNAs, which binding to the 3'UTR could be
affected by the presence of specific SNVs. We used analogs and inhibitors of
these miRNAs to test this possibility. RESULTS: We identified 11 new SNVs showing
significant association with non-FH-GH. We show that the presence of 4 of these
SNVs leads to significant changes in the transcriptional levels of the reporter
gene. Through mechanistic analysis, we identified 2 miRNAs (miR-27a and miR-133
3p) targeting the 3'UTR of sterol regulatory element-binding protein 2 and an
additional miRNA (miR-92a) targeting the 3'UTR of low-density lipoprotein
receptor-related protein-associated protein 1. CONCLUSION: Our findings reveal
novel regulatory links between certain miRNAs and key genes regulating
cholesterol homeostasis. They also highlight the potential of miRNAs as
therapeutic targets for the treatment of FH.
PMID- 28502513
TI - Relationship between noninvasive scores of nonalcoholic fatty liver disease and
nuclear magnetic resonance lipoprotein abnormalities: A focus on atherogenic
dyslipidemia.
AB - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is an emerging, highly
prevalent, cardiovascular risk factor, and lipoprotein proatherogenic
disturbances likely explain a large part of this risk. However, information
regarding associations between detailed nuclear magnetic resonance (NMR)
lipoprotein changes and noninvasive NAFLD scores is lacking. OBJECTIVE: The
objective of the study was to investigate the NMR-assessed atherogenic
lipoprotein profile according to noninvasive NAFLD status. METHODS: Lipoprotein
profiles by NMR spectroscopy and NAFLD status by fatty liver index (FLI) and
Gholam's models. RESULTS: We assessed 173 participants (55% males), mean age 60.8
+/- 7.8 years, 87% overweight/obese, 53% with diabetes. An FLI <30, 30 to 60, and
>60 was found in 32, 50, and 91 participants, respectively. Individuals with FLI
>60 had lower high-density lipoprotein (HDL)-cholesterol (P < .001), higher
triglyceride (P < .001), and similar non-HDL-cholesterol (P = .912)
concentrations. In NMR analysis, FLI was related with very-low-density
lipoprotein (VLDL) and HDL parameters in a dose-dependent manner. VLDL particle
number (P < .001) and VLDL size (39.1 +/- 0.99, 39.7 +/- 0.96, 40.8 +/- 1.19 nm,
P < .001) increased with increased FLI (<30, 30-60, and >60, respectively).
Conversely, although total HDL particle number did not differ by FLI (P = .377),
larger HDL particles (P < .001), amount of cholesterol within HDL particles (P <
.001), and HDL size (median [p25-p75]: 8.23 [8.08-8.41], 8.12 [8.03-8.29], 8.04
[7.93-8.16] nm, P < .001) decreased as FLI increased. FLI >60 (vs <60) was
associated with a higher proportion of small LDL particles (P = .010) and lower
LDL size (19.85 +/- 0.34 vs 19.98 +/- 0.25 nm; P = .005). Similar findings were
found for Gholam's model. CONCLUSION: Simple and noninvasive NAFLD scores are
useful to detect many of the proatherogenic changes (especially in VLDL and HDL),
beyond conventional lipids parameters that are common in individuals with this
high-risk condition.
PMID- 28502512
TI - Metreleptin therapy lowers plasma angiopoietin-like protein 3 in patients with
generalized lipodystrophy.
AB - BACKGROUND: Reduced triglyceride clearance due to impaired lipoprotein lipase
mediated lipolysis contributes to severe hypertriglyceridemia in lipodystrophy.
Angiopoietin-like protein 3 (ANGPTL3) and 4 (ANGPTL4) impair clearance of
triglycerides by inhibiting lipoprotein lipase. Whether circulating ANGPTL3/4
levels are altered in lipodystrophy and the effects of leptin replacement on
these ANGPTLs are unknown. OBJECTIVE: To examine if ANGPTL3/4 levels are elevated
in patients with generalized lipodystrophy and assess the effects of leptin
replacement on these ANGPTLs. METHODS: Preleptin treatment plasma levels of
ANGPTLs in patients with generalized lipodystrophy (n = 22) were compared with
healthy controls (n = 39) using a post hoc case-control study design. In a
prospective open-label study, we studied the effects of metreleptin therapy (16
32 weeks) on plasma ANGPTL3/4 in patients with generalized lipodystrophy.
RESULTS: Plasma ANGPTL3 (geometric mean [95% confidence interval]; 223 [182-275]
vs 174 ng/mL [160-189], P = .02) but not ANGPTL4 levels (55 [37-81] vs 44 ng/mL
[37-52], P = .26) were higher in patients with lipodystrophy compared with
healthy controls. There was a significant decrease in total cholesterol,
triglycerides, and glycosylated hemoglobin (A1C) levels following metreleptin
therapy. After metreleptin, ANGPTL3 concentrations decreased significantly (223
[182-275] vs 175 ng/mL [144-214], P = .01) with no change in ANGPTL4 (55 [37-81]
vs 48 ng/mL [32-73], P = .11). CONCLUSIONS: These findings suggest that elevated
plasma levels of ANGPTL3 in leptin-deficient states is attenuated with leptin
therapy.
PMID- 28502514
TI - Dyslipidemia, weight gain, and decreased growth velocity in a 14-year-old male.
AB - A 14-year-old male was referred for dyslipidemia. His findings were consistent
with metabolic syndrome. Although he lacked the typical physical appearance, his
accelerated weight gain combined with a decreased linear growth velocity
suggested Cushing syndrome. He was subsequently found to have adrenocorticotropic
hormone-independent Cushing syndrome secondary to primary pigmented nodular
adrenal disease without Carney Complex. After bilateral adrenalectomy, his lipid
profile returned to normal. In this article, we discuss the role of
glucocorticoids on lipid and lipoprotein metabolism.
PMID- 28502515
TI - Lysosomal acid lipase deficiency in all siblings of the same parents.
AB - We present 4 normal-weight sibling children with lysosomal acid lipase deficiency
(LAL-D). LAL-D was considered in the differential diagnosis based on the absence
of secondary causes and primary inherited traits for their marked hyperlipidemia,
together with unexplained hepatic transaminase elevation. Residual lysosomal acid
lipase activity confirmed the diagnosis. DNA sequencing of LIPA indicated that
the siblings were compound heterozygotes (c.894G>A and c.428+1G>A). This case
describes the unusual occurrence of all offspring from the same nonconsanguineous
mother and father inheriting compound heterozygosity of a recessive trait and the
identification of an apparently unique LIPA mutation (c.428+1G>A). It highlights
the collaborative effort between a lipidologist and gastroenterologist in
developing a differential diagnosis leading to the confirmatory diagnosis of this
rare, life-threatening disease. With the availability of an effective enzyme
replacement therapy (sebelipase alfa), LAL-D should be entertained in the
differential diagnosis of children, adolescents, and young adults with idiopathic
hyperlipidemia and unexplained hepatic transaminase elevation.
PMID- 28502516
TI - Detecting familial hypercholesterolemia: The Jack and the Beanstalk principle.
AB - We report the case of an 8-year-old girl who was fortuitously diagnosed with
familial hypercholesterolemia (FH) while being investigated for obesity. She had
a fasting total cholesterol of 11.8 mmol/L and a low-density lipoprotein
cholesterol level of 10.3 mmol/L. Her mother and maternal grandmother both had a
history of hypercholesterolemia and had developed extensive xanthelasma
palpebrarum from early adult life. Reverse cascade testing of first-degree and
second-degree relatives diagnosed a further 6 individuals with FH within the
family. We discuss the benefits of diagnosing FH in childhood, for the individual
and the wider family network ("the beanstalk") and present the rationale for
implementing a universal screening program for FH in childhood.
PMID- 28502517
TI - Questions to the article by Boyer et al.
PMID- 28502518
TI - [Management of acute exacerbations of chronic obstructive pulmonary disease
(COPD). Guidelines from the Societe de Pneumologie de Langue Francaise
(Argumentary)].
PMID- 28502519
TI - [Blomia tropicalis: A house dust mite in the tropics].
AB - INTRODUCTION: Blomia tropicalis is a mite that belongs to the superfamily of
Glycyphagidae. Initially described as a storage mite, it is now considered as a
house dust mite of tropical and sub-tropical areas. STATE OF THE ART:
Sensitization to this mite is very common in South America and Southeast Asia.
Epidemiological studies have also found sensitization to this mite in Africa and
Central America. Blo t 5 is the major allergen of B. tropicalis. Co-sensitization
to other house dust mites such as Dermatophagoides pteronyssinus (Der p) and
Dermatophagoides farinae (Der f) is very common. Cross-reactivity has been
described but recombinant allergens revealed by molecular biology techniques do
not explain this cross-reactivity. Sensitization to B. tropicalis seems to begin
at the age of 36 months, the incidence increases until adulthood, and decreases
from the age of 50. The involvement of B. tropicalis in allergic rhinitis and
asthma is well described. It is also implicated in other allergic diseases. Few
studies have assessed the therapeutic strategies available against this mite but
immunotherapy is widely used. PERSPECTIVES: Studies are needed to better
understand the role of B. tropicalis in human diseases and to develop specific
treatments.
PMID- 28502520
TI - [Exploring the diaphragm: Ultrasound is essential].
AB - The diaphragm is the muscle most implicated in breathing. Its morphological
exploration usually depends on pulmonary radiography, fluoroscopy, CT-scanning
and MRI. Its function is evaluated by the classical respiratory functional tests,
the measurement of maximum inspiratory and expiratory pressures, the
transdiaphragmatic pressure and even an electromyogram. Ultrasound is a technique
still insufficiently used in respiratory medicine. It offers, however, many
advantages: it is easy to implement, there is no irradiation, it is usable at the
bedside, particularly when the patient is immobile or in intensive care. The
results of the examination are immediately available. It allows morphological and
dynamic study of each hemidiaphragm as well as providing invaluable information
on the thoracic and subdiaphragmatic environment. Its field of exploration is
extremely wide: raised hemidiaphragm, dyspnea following a stroke or a surgical
procedure (thoracic or abdominal), road accident trauma, diagnosis and follow-up
of a paresis or paralysis, evaluation of diaphragmatic mobility during the course
of COPD (Chronic Obstructive Pulmonary Disease) and many other pathologies.
Ultrasound is insufficiently used in pleural disease and even less so in the
evaluation of the morphology and function of the diaphragm.
PMID- 28502521
TI - [Extracorporeal life support in thoracic surgery: What are the indications and
the pertinence?]
AB - INTRODUCTION: In thoracic surgery, extracorporeal life support (ECLS)
technologies are used in cases of severe and refractory respiratory failure or as
intraoperative cardiorespiratory support. The objectives of this review are to
describe the rationale of ECLS techniques, to review the pulmonary diseases
potentially treated by ECLS, and finally to demonstrate the efficacy of ECLS,
using recently published data from the literature, in order to practice evidence
based medicine. STATE OF THE ART: ECLS technologies should only be undertaken in
expert centers. ECLS allows a protective ventilatory strategy in severe ARDS. In
the field of lung transplantation, ECLS may be used successfully as a bridge to
transplantation, as intraoperative cardiorespiratory support or as a bridge to
recovery in cases of severe primary graft dysfunction. In general thoracic
surgery, ECLS technology seems to be safe and efficient as intraoperative
respiratory support for tracheobronchial surgery or for severe respiratory
insufficiency, without significant increase in perioperative risk. PERSPECTIVE:
The indications for ECLS are going to increase. Future improvements both in
scientific knowledge and bioengineering will improve the prognosis of patients
treated with ECLS for respiratory failure. Multicenter randomized controlled
trials will refine the indications for ECLS and improve the global care
strategies for these patients. CONCLUSION: ECLS is an efficient therapeutic
strategy that will improve the prognosis of patients suffering from, or exposed
to, the risks of severe respiratory failure.
PMID- 28502522
TI - Human herpesvirus 8-related diseases: Histopathologic diagnosis and disease
mechanisms.
AB - The emergence of HIV/AIDS more than three decades ago led to an increased
incidence of diseases caused by HHV8 co-infection, particularly Kaposi sarcoma,
primary effusion lymphoma, and multicentric Castleman disease. Over time, the
development of highly effective AIDS therapies has resulted in a decreased
incidence of HHV8-associated entities, which are now more commonly found in
patients with undiagnosed and/or untreated AIDS. Due to their rarity, some of
these diseases may be difficult to recognize without appropriate clinical
information. This article provides an overview of HHV8-related disorders, with a
focus on their morphologic and phenotypic features, and includes a brief overview
of laboratory methods used to detect HHV8. Disease mechanisms by which the HHV8
virion promotes tumorigenesis are also reviewed.
PMID- 28502523
TI - Human immunodeficiency virus: Diagnostic approach.
AB - First descriptions of acquired immunodeficiency syndrome appeared in 1981. Four
years later the causative agent was cultured which lead to development and
production of tests that helped healthcare providers to identify persons living
with HIV. Currently, diagnosis of HIV is performed with fourth generation
immunoassays (those that detect p24 antigen together with IgM and IgG antibodies
to HIV-1 and -2) which if positive need to be followed by an assay that can
differentiate between HIV-1 and HIV-2 viruses. The Western blot is no longer used
to confirm HIV infections per CDC guidelines. In case there is a positive fourth
generation assay but negative differentiation assay, nucleic acid testing for HIV
1 should be performed. This algorithm allows for detection of acute infections.
Alternatively, the World Health Organization has algorithms that use rapid
testing for diagnosis of HIV infections. This review will describe the evolution
of tests and diagnostic algorithms from the 1980s to the current state. Special
situations regarding diagnosis will also be discussed.
PMID- 28502524
TI - Human chorionic villous mesenchymal stem/stromal cells modify the effects of
oxidative stress on endothelial cell functions.
AB - Mesenchymal stem/stromal cells derived from chorionic villi of human term
placentae (pMSCs) produce a unique combination of molecules, which modulate
important cellular functions of their target cells while concurrently suppressing
their immune responses. These properties make MSCs advantageous candidates for
cell-based therapy. Our first aim was to examine the effect of high levels of
oxidative stress on pMSC functions. pMSCs were exposed to hydrogen peroxide
(H2O2) and their ability to proliferate and adhere to an endothelial cell
monolayer was determined. Oxidatively stressed pMSCs maintained their
proliferation and adhesion potentials. The second aim was to measure the ability
of pMSCs to prevent oxidative stress-related damage to endothelial cells.
Endothelial cells were exposed to H2O2, then co-cultured with pMSCs, and the
effect on endothelial cell adhesion, proliferation and migration was determined.
pMSCs were able to reverse the damaging effects of oxidative stress on the
proliferation and migration but not on the adhesion of endothelial cells. These
data indicate that pMSCs are not only inherently resistant to oxidative stress,
but also protect endothelial cell functions from oxidative stress-associated
damage. Therefore, pMSCs could be used as a therapeutic tool in inflammatory
diseases by reducing the effects of oxidative stress on endothelial cells.
PMID- 28502525
TI - Editorial.
PMID- 28502526
TI - Long-term preservation of eri and ailanthus silkworms using frozen gonads.
AB - Cryopreservation of eri and ailanthus silkworms using frozen gonads was
investigated. First, we evaluated the freeze tolerance of ovary and testis in the
eri silkworm, which showed high tolerance. Mating between frozen ovary
transplanted females and frozen testis-transplanted males produced 163.0 eggs,
yielding 105.7 larvae per moth. In a second experiment, we tested the use of the
eri silkworm as a host insect for gonad transplantation from ailanthus silkworm
donors. A high success ratio for laid and hatched eggs was demonstrated for ovary
transplantation (97.8 and 51.3 eggs per moth, respectively). For testis
transplantation, however, the average number of hatched larvae was low (12.0).
Mating between host eri females and males in which both frozen ovary and testis
of the ailanthus silkworm had been transplanted produced 6.4 fertilized eggs per
host moth. Our success in using cross subspecies cryopreservation between these
wild silkworms could lead to the alternative use of hosts between species in
other insects.
PMID- 28502527
TI - Effects of different sucrose concentrations on vitrified porcine preantral
follicles: Qualitative and quantitative analysis.
AB - The aim of the present study was to perform a qualitative and quantitative
analysis of the effect of different sucrose concentrations combined with ethylene
glycol in the preservation of vitrified porcine preantral follicles. Fragments of
ovarian cortex were vitrified in cryotubes containing 200 MUl of the
vitrification solution (30% Ethylene Glycol; 20% Fetal Bovine Serum; 0 M-0.25 M -
0.75 M or 1 M sucrose) and stored in liquid nitrogen for a week. Histological
analysis showed that after vitrification the number of normal follicles decreased
compared to the fresh tissue (control). The percentage of normal primordial
follicles was sucrose dose dependent. The percentage of normal primary follicles
was similar in 0 M or 0.25 M sucrose, while higher concentrations (0.75 M and 1
M) increased significantly the percentage of abnormal follicles (p < 0.05).
Morphometric analysis showed a statistically significant reduction in the total
area of primordial follicles with 0.75 M sucrose and a significant increase in
the cytoplasmic area of primordial follicles with 0 M sucrose (p < 0.05). The
qualitative and the quantitative analysis appear to be a complementary tool when
choosing a vitrification protocol. For our cryopreservation system -
vitrification of ovarian cortex slices in cryotubes-the best vitrification medium
was TCM 199-Hepes with 30% de ethylene glycol, 20% of Fetal Bovine Serum and 0 or
0.25 M sucrose. The present study shows that the use of high sucrose
concentrations in the vitrification solution has a deleterious effect on the
preservation of porcine preantral follicles contained in ovarian tissue.
Consequently, its use at 0.75 M or 1 M wouldn't be recommended.
PMID- 28502528
TI - Neural response to catecholamine depletion in remitted bulimia nervosa: Relation
to depression and relapse.
AB - Bulimia nervosa has been associated with a dysregulated catecholamine system.
Nevertheless, the influence of this dysregulation on bulimic symptoms, on neural
activity, and on the course of the illness is not clear yet. An instructive
paradigm for directly investigating the relationship between catecholaminergic
functioning and bulimia nervosa has involved the behavioral and neural responses
to experimental catecholamine depletion. The purpose of this study was to examine
the neural substrate of catecholaminergic dysfunction in bulimia nervosa and its
relationship to relapse. In a randomized, double-blind and crossover study
design, catecholamine depletion was achieved by using the oral administration of
alpha-methyl-paratyrosine (AMPT) over 24 h in 18 remitted bulimic (rBN) and 22
healthy (HC) female participants. Cerebral blood flow (CBF) was measured using a
pseudo continuous arterial spin labeling (pCASL) sequence. In a follow-up
telephone interview, bulimic relapse was assessed. Following AMPT, rBN
participants revealed an increased vigor reduction and CBF decreases in the
pallidum and posterior midcingulate cortex (pMCC) relative to HC participants
showing no CBF changes in these regions. These results indicated that the
pallidum and the pMCC are the functional neural correlates of the dysregulated
catecholamine system in bulimia nervosa. Bulimic relapse was associated with
increased depressive symptoms and CBF reduction in the
hippocampus/parahippocampal gyrus following catecholamine depletion. AMPT-induced
increased CBF in this region predicted staying in remission. These findings
demonstrated the importance of depressive symptoms and the stress system in the
course of bulimia nervosa.
PMID- 28502530
TI - The Operating Room of the Future Versus the Future of the Operating Room.
AB - Technological advancement in the operating room is evolving into a dynamic system
mirroring that of the aeronautics industry. Through data visualization,
information is continuously being captured, collected, and stored on a scalable
informatics platform for rapid, intuitive, iterative learning. The authors
believe this philosophy (paradigm) will feed into an intelligent informatics
domain fully accessible to all and geared toward precision, cell-based therapy in
which tissue can be targeted and interrogated in situ. In the future, the
operating room will be a venue that facilitates this real-time tissue
interrogation, which will guide in situ therapeutics to restore the state of
health.
PMID- 28502532
TI - Retraction.
PMID- 28502531
TI - Technological Advances in Sinus and Skull Base Surgery.
PMID- 28502533
TI - Harnessing Technology at the Edges of Otolaryngology.
PMID- 28502529
TI - Mechanisms underlying the early risk to develop anxiety and depression: A
translational approach.
AB - Anxious temperament (AT) is an early life disposition that markedly increases the
risk to develop stress related psychopathology such as anxiety and depressive
disorders. Since anxiety and depression are common, and frequently have their
onset early in life, a better understanding of the factors related to their
childhood onset will facilitate the development of new more effective neurally
informed interventions. A nonhuman primate (NHP) developmental model of childhood
AT has been established, which has provided an understanding of the neural
systems and molecular mechanisms mediating the development of AT. Multimodal
neuroimaging studies reveal altered brain metabolism across prefrontal, limbic
(e.g. central nucleus of the amygdala (Ce) and anterior hippocampus), and
brainstem regions, as well as altered functional connectivity involving the Ce.
Heritability studies demonstrate that individual variation in AT is heritable,
and genetic correlational analyses demonstrate that metabolism in the posterior
orbital frontal cortex, the bed nucleus of the stria terminalis, and the
periaqueductal gray share a genetic substrate with AT. On a molecular level, the
finding of reduced expression of Ce neuroplasticity genes provides the basis for
a neurodevelopmental hypothesis focused on the Ce. Viral vector methods for
altering gene expression in the Ce of young NHPs are currently being used as a
prelude to conceptualizing novel molecularly targeted early life interventions.
PMID- 28502534
TI - Disrupted self in Alzheimer's disease: Beyond midline structures: Commentary on
Wong et al.
PMID- 28502535
TI - Even "Cementless" Surgeons Use Cement.
AB - BACKGROUND: Patients presenting with hip arthritis have huge variability in
anatomy, bone quality, and functional expectation. These can contribute to a
varying degree of complexity on both the femoral and acetabular sides. Surgeons
should be aware of all the various options in fixation, bearing surface, and
surgical technique. METHODS: In this article, based on a presentation given at
the recent American Association of Hip and Knee Surgeons meeting in Dallas, we
will discuss why and how cemented fixation can, and indeed should, be considered
when making decisions regarding how a primary, complex primary, or revision hip
arthroplasty should be performed. RESULTS: We will review the evidence, surgical
technique, and indications for cemented fixation in primary and complex primary
surgery. In addition, we will discuss the potential benefits at revision of
previous cemented fixation. CONCLUSION: We hope to support the concept that even
cementless surgeons should also use cement.
PMID- 28502536
TI - Results of a Modular Revision System in Total Knee Arthroplasty.
AB - BACKGROUND: Revision total knee arthroplasty (TKA) poses unique challenges
compared with primary TKA such as bone loss, deformity, and ligament instability.
Modular component options allow flexibility to deal with these complexities. The
purpose of this study was to evaluate midterm outcomes for revision TKA using a
modular revision knee system with complete interchangeability and multiple
options for augmentation, offset, constraint, and stem extensions. METHODS: A
query of our practice registry revealed 257 consented patients (274 knees and 278
TKA) with minimum 2-year follow-up who underwent aseptic revision TKA with a
modular system (Vanguard Super Stabilized Knee; Zimmer Biomet, Warsaw, IN)
between 2005 and 2013. Four patients were rerevised to a second Vanguard Super
Stabilized Knee within the study period. Mean age was 68 years, and mean number
of previous surgeries was 2 (1-14). RESULTS: At mean follow-up of 6.0 years
(range, 2-11 years), there have been 25 aseptic revisions involving one or more
components (9.0%): 15 aseptic loosening with concomitant instability in 2, 8
others with instability, 1 with hypersensitivity, and 1 revised elsewhere for
unknown cause. Ten knees were revised for infection. Range of motion improved
from 100 degrees preoperatively to 105 degrees most recently. Knee Society
clinical scores improved from 45 to 79, and function scores from 46 to 56.
Radiographic evaluation revealed satisfactory position, fixation, and alignment
in 97% and abnormal findings in 7 knees: 4 limited to the patella, 1 tibial
radiolucency, 1 femoral and tibial radiolucency, and 1 tibial subsidence.
CONCLUSION: The results of this modular TKA revision system at 6 years mean
follow-up are promising for use in complex scenarios, with a low frequency of
aseptic rerevision, good knee stability, and substantial improvements in range of
motion and clinical and functional outcomes.
PMID- 28502539
TI - Racial differences in functional decline in peripheral artery disease and
associations with socioeconomic status and education.
AB - OBJECTIVE: The objective of this study was to determine whether blacks with lower
extremity peripheral artery disease (PAD) have faster functional decline than
whites with PAD. METHODS: Participants with ankle-brachial index <0.90 were
identified from Chicago medical centers and observed longitudinally. Mobility
impairment and the 6-minute walk were assessed at baseline and every 6 to 12
months. Mobility loss was defined as becoming unable to walk up and down a flight
of stairs or to walk 1/4 mile without assistance. RESULTS: Of 1162 PAD
participants, 305 (26%) were black. Median follow-up was 46.0 months. Among 711
PAD participants who walked 6 minutes continuously at baseline, black
participants were more likely to become unable to walk 6 minutes continuously
during follow-up (64/171 [37.4%] vs 156/540 [28.9%]; log-rank, P = .006). Black
race was associated with becoming unable to walk 6 minutes continuously,
adjusting for age, sex, ankle-brachial index, comorbidities, and other
confounders (hazard ratio, 1.45; 95% confidence interval, 1.05-1.99; P = .022).
This association was attenuated after adjustment for income and education (P =
.229). Among 844 participants without baseline mobility impairment, black
participants had a higher rate of mobility loss (64/209 [30.6%] vs 164/635
[25.8%]; log-rank, P = .009). Black race was associated with increased mobility
loss, adjusting for potential confounders (hazard ratio, 1.42; 95% confidence
interval, 1.04-1.94; P = .028). This association was attenuated after additional
adjustment for income and education (P = .392) and physical activity (P = .113).
There were no racial differences in average annual declines in 6-minute walk,
usual-paced 4-meter walking velocity, or fast-paced 4-meter walking velocity.
CONCLUSIONS: Black PAD patients have higher rates of mobility loss and becoming
unable to walk for 6 minutes continuously. These differences appear related to
racial differences in socioeconomic status and physical activity.
PMID- 28502540
TI - Trends and outcomes in endovascular and open surgical treatment of visceral
aneurysms.
AB - OBJECTIVE: Visceral artery aneurysms (VAAs) are rare but often repaired because
of dire consequences of rupture. This is a population-based evaluation of
chronologic trends in management, risk factors, and outcomes of endovascular and
open therapy. METHODS: The 2003 to 2013 Agency for Healthcare Research and
Quality (AHRQ) National Inpatient Sample (NIS) database was reviewed. Cases with
primary diagnosis of VAA and undergoing endovascular or open repair were
identified. Patients with renal artery or abdominal or thoracoabdominal aortic
disease were excluded. Case numbers of respective techniques were charted over
time. Baseline characteristics and in-hospital outcomes were compared for
endovascular and open groups using chi2 test, Fisher exact test, or t-test.
Predictors of mortality and complications were evaluated with multivariate
logistic regression. RESULTS: There were 9260 interventions for VAAs from 2003 to
2013, including 5166 endovascular and 4094 open. Endovascular repairs increased
from 5.3 to 24.7 per 10 million U.S. population (P < .001), surpassing open
repairs in 2008, which decreased from 14.3 to 9.2 per 10 million (P < .001).
Endovascular patients were more likely to have been treated at urban teaching
hospitals (77.1% vs 61.8%; P < .0001); to have higher proportions of renal
failure (7.6% vs 4.9%; P = .02), liver disease (11.3% vs 6.6%; P < .001), alcohol
abuse (13.1% vs 3.6%; P < .001), chronic blood loss anemia (4.5% vs 1.6%; P <
.001), metastatic cancer (2.7% vs 0.8%; P = .003), solid tumor without metastases
(3.6% vs 2.0%; P < .037), and weight loss (9.8% vs 5.2%; P < .001); and less
likely to have had elective admission (28.9% vs 59.8%; P < .0001). In-hospital
mortality (4.1% vs 4.5%; P = .618) and overall complication rates (37.8% vs
38.8%; P = .688) were similar between groups; however, pulmonary complications
were decreased for endovascular patients (10.6% vs 19.7%; P < .001). Endovascular
patients had shorter hospital stays (6.5 vs 8.7 days; P < .001). Multivariate
adjustment for mortality predictors, including coagulopathy (odds ratio [OR],
4.34; confidence interval [CI], 2.56-7.35; P < .001), liver disease (OR, 2.25;
CI, 1.25-4.07; P = .01), fluid and electrolyte disorders (OR, 2.84; CI, 1.73
4.66; P < .001), and solid tumor without metastases (OR, 2.81; CI, 1.10-7.18; P =
.03), showed that open treatment was associated with increased mortality (OR,
1.70; CI, 1.03-2.81; P = .04). Analysis of overall complications revealed that
open treatment was again associated with increased complications (OR, 1.78; CI,
1.43-2.21; P < .001). CONCLUSIONS: Endovascular VAA repairs are increasing.
Despite patients' having worse comorbidities and more nonelective admissions,
endovascular therapy appears to be associated with decreased mortality and
complications and shorter hospital stays.
PMID- 28502541
TI - Prolonged stance phase during walking in intermittent claudication.
AB - BACKGROUND: Patients with intermittent claudication (IC) tend to walk slower and
consume approximately 40% more oxygen during walking compared with healthy
individuals. An unfavorable locomotion pattern has been suggested to explain this
metabolic inefficiency. However, detailed knowledge of gait parameters in IC is
lacking. METHODS: In a cross-sectional study, the gait pattern of newly diagnosed
IC patients was compared with that of healthy controls. Spatiotemporal gait
parameters such as step length and duration of stance phase were obtained by a
photoelectric technique (OptoGait; Microgate, Bolzano, Italy). This system was
previously found to have favorable concurrent validity and test-retest
reliability characteristics. Parameters were determined during pain-free and
painful treadmill walking at a comfortable self-determined walking pace. Each
parameter was averaged on the basis of 80 steps. RESULTS: A total of 28 patients
and 28 controls were examined. IC patients walked 1.2 km/h (-27%) slower than
controls (P < .001), coinciding with a significantly shorter step length (-20%)
and lower cadence (-11%). IC patients demonstrated a longer stance and double
support phase, even before the onset of ischemic pain. Differences were also
observed in segments of the stance phase, as a 14% shorter propulsion (P < .001)
and 17% longer flat foot phase (P < .001) during painful walking were found. In
considering the absolute duration of these stance phase segments, differences
were found only for the flat foot time (Delta0.10 second; P < .001). CONCLUSIONS:
Patients with IC demonstrate an altered gait pattern compared with healthy
controls. The most prominent differences were a prolonged relative and absolute
duration of the flat foot position during the stance phase. This adaptation may
be intuitive as an augmented arterial blood flow into skeletal muscles is allowed
during a prolonged relaxation phase. Therefore, not only the lack of propulsion
but also a gain of relaxation may explain these gait alterations.
PMID- 28502542
TI - Contemporary evaluation of mortality and stroke risk after thoracic endovascular
aortic repair.
AB - OBJECTIVE: During the past decade, thoracic endovascular aortic repair (TEVAR)
has increased as a treatment option for a variety of aortic pathologic processes.
Despite this rise in the use of thoracic stent grafts, real-world outcomes from a
robust, adjudicated, contemporary data set have yet to be reported. Previous
studies have shown periprocedural mortality rates between 1.5% and 9.5% and
procedure-related stroke rates of 2.3% to 8.2%. With advances in device
engineering and increased experience of physicians, we hypothesized that the
rates of these complications would be reduced in a more recent sample set. The
purpose of this study was to determine current rates of mortality and stroke
after TEVAR, to identify risk factors that contribute to 30-day mortality, and to
develop a simple scoring system that allows risk stratification of patients
undergoing TEVAR. METHODS: We examined the 30-day mortality rate after TEVAR
using the 2013 to 2014 American College of Surgeons National Surgical Quality
Improvement Program database. Patients undergoing TEVAR for all aortic disease
were identified using procedure codes. Bivariate analyses were performed to
evaluate the association of preoperative, intraoperative, and postoperative
variables with 30-day mortality, followed by multivariable logistic analysis
using preoperative variables only, with P < .10 as the criterion for model entry.
The predictive logistic model was internally validated by cross-validation.
Variables included in the multivariable model were used to develop a risk score.
RESULTS: There were 826 patients included. The 30-day mortality and stroke rates
were 7.63% (n = 63) and 4.5% (n = 37), respectively. In regression analysis,
mortality was independently associated with age >=80 years (odds ratio [OR],
2.32; 95% confidence interval [CI], 1.25-4.31), emergency case (OR, 2.61; 95% CI,
1.39-4.90), American Society of Anesthesiologists classification >3 (OR, 2.89;
95% CI, 1.34-6.24), transfusion >4 units in the 72 hours before surgery (OR,
2.86; 95% CI, 1.30-6.28), preoperative creatinine concentration >=1.8 mg/dL (OR,
2.07; 95% CI, 1.05-4.08), and preoperative white blood cell count >=12 * 109/L
(OR, 2.65; 95% CI, 1.41-4.96). Incorporating these factors, a 6-point risk score
was generated and demonstrated high predictability for overall 30-day mortality.
CONCLUSIONS: Recent data from a national, retrospective data set demonstrate that
high perioperative mortality and stroke rates have persisted during the last
decade. The risk score derived from this data set is simple and convenient and
serves as a prognostic tool in the preoperative risk stratification of patients
being evaluated for TEVAR.
PMID- 28502543
TI - The association of Carotid Revascularization Endarterectomy versus Stent Trial
(CREST) and Centers for Medicare and Medicaid Services Carotid Guideline
Publication on utilization and outcomes of carotid stenting among "high-risk"
patients.
AB - OBJECTIVE: Since the 2004 approval by the United States Food and Drug
Administration of carotid artery stenting (CAS), there have been two seminal
publications about CAS reimbursement (Centers for Medicare and Medicaid Services
guidelines; 2008) and clinical outcomes (Carotid Revascularization Endarterectomy
versus Stent Trial [CREST]; 2010). We explored the association between these
publications and national trends in CAS use among high-risk symptomatic patients.
METHODS: The most recent congruent data sets of the Nationwide Inpatient Sample
(NIS) were queried for patients undergoing carotid revascularization. The sample
was limited to include only patients who were defined as "high-risk" if they had
a Charlson Comorbidity Score of >=3.0. Subgroup analyses were performed of high
risk patients with symptomatic carotid stenosis. Utilization proportions of CAS
were calculated quarterly from 2005 to 2011 for NIS. Three time intervals related
to Centers for Medicare and Medicaid Services guidelines and CREST publication
were selected: 2005 to 2008, 2008 to 2010, and after 2010. Logistic regression
with piecewise linear trend for time was used to estimate different trends in CAS
use for the overall high-risk sample and for neurologically asymptomatic and
symptomatic cases. Multivariate logistic regression was used to compare odds of
postoperative mortality and stroke between these two procedures at different time
intervals independent of confounding variables. RESULTS: During the study period,
20,079 carotid endarterectomies (CEAs) and 3447 CAS procedures were performed in
high-risk patients in the NIS database. CAS utilization constituted 20.5% of
carotid revascularization procedures among high-risk symptomatic patients, with a
significant increase from 18.6% to 24.4% during the study period (P < .001).
There was an initial increase during 2005 to 2008 in the rate of CAS compared
with CEA, CAS utilization significantly decreased during 2008 to 2010 by a 3.3%
decline in the odds ratio (OR) of CAS per quarter (OR, 0.967; 95% confidence
interval [CI], 0.943-0.993; P = .002), and after CREST (after 2010), CAS
utilization continued to increase significantly from the prepublication to the
postpublication time interval. The odds of in-hospital mortality (OR, 2.56; 95%
CI, 1.17-5.62; P = .019) and postoperative in-hospital stroke (OR, 1.53; 95% CI,
1.09-3.68; P = .024) were independently and significantly higher for CAS patients
in the overall sample. CONCLUSIONS: The use of CAS for carotid revascularization
in a high-risk cohort of patients has significantly increased from 2005 to 2011.
Compared with CEA, CAS independently increased the odds of perioperative in
hospital stroke in all high-risk patients and of in-hospital mortality in
symptomatic high-risk patients.
PMID- 28502545
TI - Durability of iliac artery preservation associated with endovascular repair of
infrarenal aortoiliac aneurysms.
AB - OBJECTIVE: This study evaluated and compared the long-term clinical outcomes of
endovascular repair of infrarenal aortoiliac aneurysms (EVAR) vs EVAR with
preservation of antegrade internal iliac artery (IIA) perfusion using iliac
branched devices (EVAR-IBDs). METHODS: From October 1998 to August 2015, patients
with infrarenal aortoiliac aneurysmal (AIA) disease at high risk for conventional
open surgery were enrolled in a prospective physician-sponsored investigational
device exemption trial. Clinical data of 75 patients treated with EVAR-IBD and
255 with standard EVAR were analyzed. Technical success, perioperative outcomes,
mortality, device patency, endoleak rates, and reinterventions during a follow-up
of 10 years were analyzed. RESULTS: There were 87 IBDs deployed in 75 patients.
Technical success rate was 97%. Mortality at 30 days was 1.3%. Freedom from
aneurysm-related mortality at 3, 5, and 10 years was 99%. Freedom from a type I
or III endoleak at 3, 5, and 10 years was 99%. Freedom from secondary
reinterventions at 3, 5, and 10 years was 86%, 81%, and 81%, respectively.
Primary patency of the IBDs at 3, 5, and 10 years was 94%, 94%, and 77%,
respectively. Twenty-four percent of patients underwent EVAR for concomitant AIA
disease (EVAR-AIA), and 78% were managed by staged IIA embolization before EVAR.
No statistically significant difference in freedom from aneurysm-related
mortality, limb occlusions, or endoleak rates was identified in patients with
EVAR-AIA vs EVAR-IBD (P > .05). There were significantly more secondary
reinterventions in the EVAR-AIA group compared with the EVAR-IBD group (hazard
ratio, 0.476, 95% confidence interval, 0.226-1.001; P = .045). CONCLUSIONS: EVAR
of infrarenal AIAs with preservation of antegrade flow to the IIA using IBDs is
feasible with long-term sustained durability. Serious considerations should be
given to the use of IBDs in patients with infrarenal AIAs meeting appropriate
anatomic criteria.
PMID- 28502544
TI - First experience with the double chimney technique in the treatment of aortic
arch diseases.
AB - OBJECTIVE: The objective of this study was to summarize our initial experience
using the double chimney technique to treat aortic arch diseases. METHODS: From
December 2009 to October 2016, 23 patients with aortic arch diseases, including
20 acute aortic dissections, 2 aortic arch aneurysms, and 1 type I endoleak after
thoracic endovascular aortic repair (TEVAR), were treated using a double chimney
technique. An emergent operation was performed in only one patient with an acute
aortic dissection for severe left lower extremity ischemia. All patients were
observed after TEVAR with computed tomography scans at 2 weeks, at 3 and 6
months, and annually thereafter. RESULTS: In all patients, aortic arch lesions
were covered, and supra-aortic branches were patent without morbidity. In 22
patients, the innominate artery (IA) and left common carotid artery were
reconstructed with the proximal landing zone in zone 0; in 1 patient, the left
common carotid artery and left subclavian artery were reconstructed. During the
procedure, there were three (13.0%) type I endoleaks. Chimney stent graft
migration occurred in one (4.3%) patient perioperatively; compression of a
chimney stent graft occurred in one (4.3%) patient 4 days after TEVAR. There were
no type II endoleaks or perioperative mortality. Median follow-up was 28.0 +/-
19.8 (range, 3-84) months, with no TEVAR-related deaths. Partial compression of
the chimney stent graft in the IA occurred at 3 months after TEVAR in one (4.3%)
patient; three patients had persistent but asymptomatic type I endoleaks.
CONCLUSIONS: TEVAR using a double chimney technique to reconstruct the supra
aortic branches provides a safe and minimally invasive alternative procedure
associated with low postoperative mortality. The main perioperative complications
include type I endoleak and compression of the chimney stent grafts in the IA.
More experience with long-term results is needed to evaluate the effectiveness
and durability of this advanced endovascular procedure.
PMID- 28502546
TI - Cryopreserved saphenous vein as a last-ditch conduit for limb salvage.
AB - OBJECTIVE: In patients lacking autogenous vein suitable for infrainguinal bypass,
cryopreserved saphenous vein (CSV) allograft (CryoLife, Inc, Kennesaw, Ga) may be
an acceptable alternative. The purpose of this study was to examine outcomes of
CSV conduit for infrainguinal revascularization. METHODS: Between February 2008
and August 2015, 70 patients underwent infrainguinal bypass grafts in 73 limbs
using CSV. All patients lacked suitable arm or leg vein. Demographic data and
patient outcomes were retrospectively collected using electronic medical records.
RESULTS: The mean age of our cohort was 70 +/- 14 years, and 36 (51%) were male;
47 (67%) were white, 39 (56%) had coronary artery disease, 27 (39%) had diabetes,
56 (80%) had hypertension, and 50 (71%) were former or current smokers. Median
follow-up was 304 days (interquartile range, 130-991 days). Indications for the
index operation included rest pain (27%), tissue loss (55%), and prosthetic graft
infection (18%); 62 of 73 (85%) bypasses were performed for critical limb
ischemia, and 45 of 73 (62%) were redo operations. Distal targets included
superficial femoral artery or popliteal (38%), tibial (55%), and pedal (7%). All
grafts had a minimum diameter of 3 mm. At 30 days, 55 of 64 grafts (86%) were
patent; 9 were lost to early follow-up. The only significant risk factors
associated with 30-day failure were ABO mismatch (43% vs 10%; P = .05) and donor
blood type B or AB (40% vs 9%; P = .03). Estimated overall 1-year primary patency
was 35%. In a multivariate analysis, nonblack race (P = .05), donor B or AB blood
type (P = .01), and bypass to a tibial or pedal target (P = .05) were
independently associated with loss of primary patency. There were 20 (27%) major
amputations, and all grafts in these limbs had occluded at the time of
amputation. Of the 33 limbs with ischemic tissue loss that had long-term follow
up, 17 of 33 (52%) went on to graft occlusion, 10 of 33 (30%) had a major
amputation, and 24 of 33 (73%) had complete healing of the index wound.
CONCLUSIONS: In the setting of a multidisciplinary team with aggressive wound
care, CSV may be a reasonable choice for infrainguinal revascularization in
patients with ischemic tissue loss who lack autogenous conduit. However, poor
midterm to long-term patency suggests that optimal selection of patients is
needed to derive meaningful clinical benefit.
PMID- 28502547
TI - Carotid artery stenting is associated with a higher incidence of major adverse
clinical events than carotid endarterectomy in female patients.
AB - BACKGROUND: The optimal approach to carotid revascularization in female patients
with carotid artery stenosis is widely debated. Information available is largely
derived from clinical trials that include only highly selected patients. The goal
of this study was to compare the early clinical outcomes in women who undergo
carotid artery stenting (CAS) vs carotid endarterectomy (CEA). METHODS: Female
patients undergoing CAS or CEA between January 1, 2012 and December 31, 2015, and
who were included in the Procedure Targeted American College of Surgeons National
Surgical Quality Improvement Program were assessed for their incidence of early
postoperative complications. The primary outcome measure was 30-day incidence of
a major adverse clinical event (MACE; defined as death, stroke, transient
ischemic attack, or myocardial infarction/arrhythmia). Univariable analyses were
used to compare results between female patients undergoing CEA and those
undergoing CAS. Propensity score matching techniques were used to create a cohort
of 125 CAS and CEA patients who were well matched for all known patient-, disease
, and procedure-related factors. Analysis of comparative outcomes between the
propensity-matched groups was then performed. RESULTS: The overall study
population consisted of 5620 female CEA patients and 131 female CAS patients. Of
these patients, 290 (5.2%) from the CEA group and 16 (12.2%) from the CAS group
sustained a MACE in the first 30 days after their procedures. Within the
propensity-matched cohort, the 30-day incidence of postoperative MACE in the CAS
group of this cohort was 11.2% (14 patients) compared with 4.0% (5 patients; odds
ratio, 1.01 [95% confidence interval, 1.01-7.77]; P = .04) in the CEA group.
CONCLUSIONS: Our analysis of a "real-world" clinical registry suggests that CAS
may be inferior to CEA in female patients who require carotid artery
revascularization.
PMID- 28502548
TI - Lifelong limb preservation: A patient-centered description of lower extremity
arterial reconstruction outcomes.
AB - BACKGROUND: Life expectancy is short for patients with critical limb ischemia
(CLI), many of whom may fear amputation more than death. In light of the reduced
life expectancy of these patients, the traditional 5-year freedom from amputation
(FFA) statistic may not accurately address their concern. We developed a more
relevant patient-centered calculation of major amputation risk during a patient's
remaining lifetime to better answer the question, Will I ever lose my leg?
METHODS: We identified all limbs undergoing first-time intervention for CLI in a
large institutional database from 2005 to 2013. We calculated the traditional
metrics of amputation-free survival (AFS, for which failure is death or
amputation) and FFA (for which failure is amputation but deaths are censored and
removed from further analysis). In addition, we propose a new term, lifelong limb
preservation (LLP). LLP defines amputation as failure, but deaths are not
censored and therefore reflect that LLP has been achieved. All deaths before 30
days were considered a failure in all three metrics, reflecting the risk of
surgery. RESULTS: There were 1006 limbs identified as having first-time
intervention for CLI (22% rest pain, 45% ulcer, 27% gangrene; 46% treated by
angioplasty with or without stenting, 54% bypass). Using life-table analysis, 7
year AFS was 14% (561 events), FFA was 78% (123 events), and LLP was 86% (123
events). LLP was similar between patients undergoing angioplasty with or without
stenting and bypass (7-year rates, 86% and 85%, respectively). For patients
undergoing intervention for rest pain, 7-year rates were 14% for AFS, 84% for
FFA, and 92% for LLP. For those undergoing treatment for ulcer, 7-year rates were
14% for AFS, 77% for FFA, and 86% for LLP. Finally, in those with gangrene, rates
were 10% for AFS, 67% for FFA, and 79% for LLP. Using LLP, patients presenting
with an ulcer can be told that although we cannot guarantee how long they will
live, with revascularization there is approximately an 86% chance they will not
lose the leg. CONCLUSIONS: These results show that the durability of our limb
preservation efforts often exceeds the life expectancy of our patients. Using LLP
as an outcomes assessment provides a more accurate and patient-centered answer to
the question, If I have this procedure, will I ever lose my leg?
PMID- 28502549
TI - Reimbursement in hospital-based vascular surgery: Physician and practice
perspective.
AB - OBJECTIVE: The purpose of this study was to determine change in value of a
vascular surgery division to the health care system during 6 years at a hospital
based academic practice and to compare physician vs hospital revenue earned
during this period. METHODS: Total revenue generated by the vascular surgery
service line at an academic medical center from 2010 through 2015 was evaluated.
Total revenue was measured as the sum of physician (professional) and hospital
(technical) net revenue for all vascular-related patient care. Adjustments were
made for work performed, case complexity, and inflation. To reflect the effect of
these variables, net revenue was indexed to work relative value units (wRVUs),
case mix index, and consumer price index, which adjusted for work, case
complexity, and inflation, respectively. Differences in physician and hospital
net revenue were compared over time. RESULTS: Physician work, measured in RVUs
per year, increased by 4%; case complexity, assessed with case mix index,
increased by 10% for the 6-year measurement period. Despite stability in payer
mix at 64% to 69% Medicare, both physician and hospital vascular-related
revenue/wRVU decreased during this period. Unadjusted professional revenue/wRVU
declined by 14.1% (P = .09); when considering case complexity, physician
revenue/wRVU declined by 20.6% (P = .09). Taking into account both case
complexity and inflation, physician revenue declined by 27.0% (P = .04).
Comparatively, hospital revenue for vascular surgery services decreased by 13.8%
(P = .07) when adjusting for unit work, complexity, and inflation. CONCLUSIONS:
At medical centers where vascular surgeons are hospital based, vascular care
reimbursement decreased substantially from 2010 to 2015 when case complexity and
inflation were considered. Physician reimbursement (professional fees) decreased
at a significantly greater rate than hospital reimbursement for vascular care.
This trend has significant implications for salaried vascular surgeons in
hospital-based settings, where the majority of revenue generated by vascular
surgery care is the technical component received by the facility. Appropriate
care for patients with vascular disease is increasingly resource intensive, and
as a corollary, reimbursement levels must reflect this situation if high-quality
care is to be maintained.
PMID- 28502550
TI - Lower extremity computed tomography angiography can help predict technical
success of endovascular revascularization in the superficial femoral and
popliteal artery.
AB - OBJECTIVE: Preprocedural computed tomography angiography (CTA) assists in
evaluating vascular morphology and disease distribution and in treatment planning
for patients with lower extremity peripheral artery disease (PAD). The aim of the
study was to determine the predictive value of radiographic findings on CTA and
technical success of endovascular revascularization of occlusions in the
superficial femoral artery-popliteal (SFA-pop) region. METHODS: Medical records
and available imaging studies were reviewed for patients undergoing endovascular
intervention for PAD between January 2013 and December 2015 at a single academic
institution. Radiologists reviewed preoperative CTA scans of patients with
occlusions in the SFA-pop region. Radiographic criteria previously used to
evaluate chronic occlusions in the coronary arteries were used. Technical
success, defined as restoration of inline flow through the SFA-pop region with
<30% stenosis at the end of the procedure, and intraoperative details were
evaluated. RESULTS: From 2013 to 2015, there were 407 patients who underwent 540
endovascular procedures for PAD. Preprocedural CTA scans were performed in 217
patients (53.3%), and 84 occlusions in the SFA-pop region were diagnosed. Ten
occlusions were excluded as no endovascular attempt to cross the lesion was made
because of extensive disease or concomitant iliac intervention. Of the remaining
74 occlusions in the SFA-pop region, 59 were successfully treated (80%) and 15
were unsuccessfully crossed (20%). The indications for revascularization were
claudication in 57% of patients and critical limb ischemia in the remaining
patients. TransAtlantic Inter-Society Consensus A, B, and C occlusions were
treated with 87% success, whereas D occlusions were treated with 68% success (P =
.047). There were nine occlusions with 100% vessel calcification that was
associated with technical failure (P = .014). Longer lengths of occlusion were
also associated with technical failure (P = .042). Multiple occlusions (P = .55),
negative remodeling (P = .69), vessel runoff (P = .56), and percentage of vessel
calcification (P = .059) were not associated with failure. On multivariable
analysis, 100% calcification remained the only significant predictor of technical
failure (odds ratio, 9.0; 95% confidence interval, 1.8-45.8; P = .008).
CONCLUSIONS: Analysis of preoperative CTA shows 100% calcification as the best
predictor of technical failure of endovascular revascularization of occlusions in
the SFA-pop region. Further studies are needed to determine the cost
effectiveness of obtaining preoperative CTA for lower extremity PAD.
PMID- 28502551
TI - Variation in hospital costs and reimbursement for endovascular aneurysm repair: A
Vascular Quality Initiative pilot project.
AB - OBJECTIVE: Comparing costs between centers is difficult because of the
heterogeneity of vascular procedures contained in broad diagnosis-related group
(DRG) billing categories. The purpose of this pilot project was to develop a
mechanism to merge Vascular Quality Initiative (VQI) clinical data with hospital
billing data to allow more accurate cost and reimbursement comparison for
endovascular aneurysm repair (EVAR) procedures across centers. METHODS: Eighteen
VQI centers volunteered to submit UB04 billing data for 782 primary, elective
infrarenal EVAR procedures performed by 108 surgeons in 2014. Procedures were
categorized as standard or complex (with femoral-femoral bypass or additional
arterial treatment) and without or with complications (arterial injury or
embolectomy; bowel or leg ischemia; wound infection; reoperation; or cardiac,
pulmonary, or renal complications), yielding four clinical groups for comparison.
MedAssets, Inc, using cost to charge ratios, calculated total hospital costs and
cost categories. Cost variation analyzed across centers was compared with DRG 237
(with major complication or comorbidity) and 238 (without major complication or
comorbidity) coding. A multivariable model to predict DRG 237 coding was
developed using VQI clinical data. RESULTS: Of the 782 EVAR procedures, 56% were
standard and 15% had complications, with wide variation between centers. Mean
total costs ranged from $31,100 for standard EVAR without complications to
$47,400 for complex EVAR with complications and varied twofold to threefold among
centers. Implant costs for standard EVAR without complications varied from $8100
to $28,200 across centers. Average Medicare reimbursement was less than total
cost except for standard EVAR without complications. Only 9% of all procedures
with complications in the VQI were reported in the higher reimbursed DRG 237
category (center range, 0%-21%). There was significant variation in hospitals'
coding of DRG 237 compared with their expected rates. VQI clinical data
accurately predict current DRG coding (C statistic, 0.87). CONCLUSIONS: VQI data
allow a more precise EVAR cost comparison by identifying comparable clinical
groups compared with DRG-based calculations. Total costs exceeded Medicare
reimbursement, especially for patients with complications, although this varied
by center. Implant costs also varied more than expected between centers for
comparable cases. Incorporation of VQI data elements documenting EVAR case
complexity into billing data may allow centers to better align respective DRG
reimbursement to total costs.
PMID- 28502552
TI - Bifurcated-bifurcated aneurysm repair is a novel technique to repair infrarenal
aortic aneurysms in the setting of iliac aneurysms.
AB - BACKGROUND: Up to 40% of abdominal aortic aneurysms (AAAs) have coexistent iliac
artery aneurysms (IAAs). In the past, successful endovascular repair required
internal iliac artery (IIA) embolization, which can lead to pelvic or buttock
ischemia. This study describes a technique that uses a readily available solution
with a minimally altered off-the-shelf bifurcated graft in the IAA to maintain
IIA perfusion. METHODS: From August 2009 to May 2015, 14 patients with AAAs and
coexisting IAAs underwent repair with a bifurcated-bifurcated approach. A 22-mm
or 24-mm bifurcated main body device was used in the IAA with extension of the
"contralateral" limb into the IIA. Intraoperative details including operative
time, fluoroscopy time, and contrast agent use were recorded. Outcome measures
assessed were operative technical success and a composite outcome measure of IIA
patency, freedom from reintervention, and clinically significant endoleak at 1
year. RESULTS: Fourteen patients underwent bifurcated-bifurcated repair during
the study period. Technical success was achieved in 93% of patients, with
successful treatment of the AAA and IAA and preservation of flow to at least one
IIA. The procedure was performed with a completely percutaneous bilateral femoral
approach in 92% of patients. Three patients had a type II endoleak on initial
follow-up imaging, but none were clinically significant. There were no cases of
bowel ischemia or erectile dysfunction. One patient had buttock claudication
ipsilateral to IIA coil embolization (contralateral to bifurcated iliac repair
and preserved IIA) that resolved by 6-month follow-up. Two patients required
reinterventions. One patient presented to his first follow-up visit on
postoperative day 25 with thrombosis of the right external iliac limb ipsilateral
to the bifurcated iliac repair, which was successfully treated with thrombectomy
and stenting of the limb. This same patient presented at 83 months with growth of
the preserved IIA to 3.9 cm and underwent coil embolization of the aneurysm.
Another patient presented for surveillance 44 months after his original repair
with component separation of the mating stent and the iliac bifurcated stent
grafts. This was treated with a limb extension and endoanchors to fuse the
endografts. Of the 13 patients who underwent bifurcated-bifurcated repair, 100%
of the preserved IIAs remained patent at last follow-up. The composite outcome
measure of IIA patency and freedom from reintervention and clinically significant
endoleak at 1 year was 92% (n = 12/13). CONCLUSIONS: In this small retrospective
review, bifurcated-bifurcated aneurysm repair of aortoiliac aneurysms with
preservation of perfusion to the IIA is technically feasible and safe with good
short-term and midterm results in male patients.
PMID- 28502553
TI - A shortened protocol for assessing cognitive bias in rats.
AB - BACKGROUND: Reliable measurement of affective state in animals is a significant
goal of animal welfare. Such measurements would also improve the validity of pre
clinical mental health research which relies on animal models. However, at
present, affective states in animals are inaccessible to direct measurement. In
humans, changes in cognitive processing can give reliable indications of
emotional state. Therefore, similar techniques are increasingly being used to
gain proxy measures of affective states in animals. In particular, the 'cognitive
bias' assay has gained popularity in recent years. Major disadvantages of this
technique include length of time taken for animals to acquire the task (typically
several weeks), negative experiences associated with task training, and issues of
motivation. NEW METHOD: Here we present a shortened cognitive bias protocol using
only positive reinforcers which must actively be responded to. RESULTS: The
protocol took an average of 4days to complete, and produced similar results to
previous, longer methods (minimum 30days). Specifically, rats housed in standard
laboratory conditions demonstrated negative cognitive biases when presented with
ambiguous stimuli, and took longer to make a decision when faced with an
ambiguous stimulus. COMPARISON WITH EXISTING METHODS: Compared to previous
methods, this protocol is significantly shorter (average 4days vs. minimum
30days), utilises only positive reinforcers to avoid inducing negative affective
states, and requires active responses to all cues, avoiding potential confounds
of motivational state. CONCLUSIONS: We have successfully developed a shortened
cognitive bias protocol, suitable for use with laboratory rats.
PMID- 28502554
TI - The 9 to 5 Rodent - Time for Change? Scientific and animal welfare implications
of circadian and light effects on laboratory mice and rats.
AB - Rodents, particularly rats and mice, are the most commonly used laboratory
animals and are extensively used in neuroscience research, including as
translational models for human disorders. It is common practice to carry out
scientific procedures on rats and mice during the daytime, which is the inactive
period for these nocturnal species. However, there is increasing evidence for
circadian and light-induced effects on rodent physiology and behaviour which may
affect the validity of results obtained from mice and rats in neuroscience
studies. For example, testing animals during their inactive periods may produce
abnormal results due to cognitive deficits, lack of motivation to perform the
task or stress from being disturbed during the resting period. In addition,
conducting procedures during an animal's resting period may also pose an animal
welfare issue, as procedures may be experienced as more stressful than if these
were done during the active phase. In this paper we set out the need to consider
the impact of time of day and lighting conditions, when scientific procedures or
routine husbandry are performed, on both the welfare of mice and rats used in
neuroscience research and on data quality. Wherever possible, husbandry and
experimental procedures should be conducted at times of day when the animals
would be active, and under naturalistic lighting conditions, to minimise stress
and maximise data quality and translatability.
PMID- 28502555
TI - Nivolumab in Second-Line Treatment for Advanced Non-Small-Cell Lung Cancer With
Squamous-Cell Histology: A Perspective Based on Pharmacologic Costs.
PMID- 28502556
TI - Morbidity and mortality conference is not sufficient for surgical quality
control: Processes and outcomes of a successful attending Physician Peer Review
committee.
AB - BACKGROUND: Physician Peer Review (PPR) is required by The Joint Commission to
assure examination of individual and group outcomes. Although surgeons may
utilize Morbidity and Mortality (M&M) conference, applying these data to
determine Focused Professional Practice Evaluations involves outcomes review. A
PPR Committee of senior surgeons was created. This report describes one
institution's surgical PPR process and results. METHOD: A two-year (2014-2015)
retrospective review of significant non-trauma complications and unanticipated
deaths evaluated by PPR was performed. A faculty questionnaire evaluated
perceptions of quality outcomes reporting. RESULTS: Of 395 reviewed cases, almost
half (48.9%) demonstrated no care improvement opportunities, 48.6% revealed
possible improvements, 2% were deviations from standard of care, and 0.5%
represented unacceptable care. Although most surgeons (94%) wanted to know their
complication rates, only 41% reported maintaining an outcomes database.
CONCLUSIONS: As a complement to M&M, PPR is a valuable tool in the evaluation of
individual surgical quality and can be the basis for further quality improvement
opportunities. This process has been largely successful; only a small number of
significant concerns were discovered.
PMID- 28502557
TI - Antecedents and early correlates of high and low concentrations of angiogenic
proteins in extremely preterm newborns.
AB - BACKGROUND: To identify the antecedents and very early correlates of low
concentrations of angiogenic proteins in the blood of extremely preterm newborns
during the first postnatal month. METHODS: Using multiplex immunoassays we
measured the concentrations of vascular endothelial growth factor A (VEGF), VEGF
receptor-1 (VEGFR-1), VEGF receptor-2 (VEGFR-2), placenta growth factor (PIGF),
and angiopoietins 1 and 2 (Ang-1, Ang-2), as well as 21 other proteins in blood
spots collected on postnatal days 1 (N=1062), 7 (N=1087), 14 (N=989), 21 (N=940)
and 28 (N=880) from infants born before the 28th week of gestation. We then
sought the protein-concentration correlates of concentrations in the top and
bottom quartile for gestational age and day the specimen was collected. RESULTS:
Children who were delivered for medical indications and those who were severely
growth restricted were more likely than others to have low day-1 blood
concentrations of VEGF, VEGF-R2, Ang-1, and PIGF. Systemic inflammation
accompanied top quartile concentrations of every one of the 6 angiogenic
proteins. CONCLUSIONS: Low day-1 concentrations of most angiogenic proteins are
associated with disorders linked to placenta insufficiency/dysfunction. High
concentrations, on the other hand, are associated with systemic inflammation
throughout the first postnatal month.
PMID- 28502558
TI - Identification of candidate biomarkers that involved in the epigenetic
transcriptional regulation for detection gastric cancer by iTRAQ based
quantitative proteomic analysis.
AB - BACKGROUND: The sensitivities and specificities of biomarkers for gastric cancer
are insufficient for clinical detection, and new diagnostics are therefore
urgently required. METHODS: A discovery set of gastric cancer tissues was labeled
with iTRAQ reagents, separated using SCX chromatography, and identified using LC
ESI-MS/MS. A validation set of gastric cancer tissues was used to confirm the
expression levels of potential markers. RESULTS: The present study detected
metastasis-associated protein 2 (MTA2) and Histone deacetylases 1 (HDAC1)
proteins that were overexpressed in gastric cancer tissues compared with that in
adjacent gastric tissue. The sensitivity and specificity of MTA2 in detecting 76
cases gastric cancers were 57.9% (95% CI: 46.5%-69.3%) and 55.3% (95% CI: 43.8%
66.7%), respectively. The sensitivity and specificity of HDAC1 were 61.8% (95%
CI: 50.7%-73%) and 63.2% (95% CI: 52.1%-74.3%), respectively. The co-expression
of MTA2 and HDAC1 in gastric cancer achieved 65.3% sensitivity (95% CI: 51.5%
79.1%) and 65.2% specificity (95% CI: 50.9%-79.5%), which was strongly associated
with lymph node metastasis and TNM staging. CONCLUSION: The present findings
indicated a tight correlation between the MTA2 and HDAC1 expression level and
lymph node metastasis and TNM staging in gastric cancers. Therefore, MTA2 and
HDAC1 might be predictors of lymph node metastasis phenotype and possible target
molecule for anticancer drug design in human gastric cancer.
PMID- 28502559
TI - 3'-UTR SNP rs2229611 in G6PC1 affects mRNA stability, expression and Glycogen
Storage Disease type-Ia risk.
AB - The frequency of rs2229611, previously reported in Chinese, Caucasians, Japanese
and Hispanics, was investigated for the first time in Indian ethnicity. We
analyzed its role in the progression of Glycogen Storage Disease type-Ia (GSD-Ia)
and breast cancer. Genotype data on rs2229611 revealed that the risk of GSD-Ia
was higher (P=0.0195) with CC compared to TT/TC genotypes, whereas no such
correlation was observed with breast cancer cases. We observed a strong linkage
disequilibrium (LD) among rs2229611 and other disease causing G6PC1 variants
(|D'|=1, r2=1). Functional validation performed in HepG2 cells using luciferase
constructs showed significant (P<0.05) decrease in expression than wild-type 3'
UTR due to curtailed mRNA stability. Furthermore, AU-rich elements (AREs)
mediated regulation of G6PC1 expression characterized using 3'-UTR deletion
constructs showed a prominent decrease in mRNA stability. We then examined
whether miRNAs are involved in controlling G6PC1 expression using pmirGLO-UTR
constructs, with evidence of more distinct inhibition in the reporter function
with rs2229611. These data suggests that rs2229611 is a crucial regulatory SNP
which in homozygous state leads to a more aggressive disease phenotype in GSD-Ia
patients. The implication of this result is significant in predicting disease
onset, progression and response to disease modifying treatments in patients with
GSD-Ia.
PMID- 28502560
TI - A microscale protocol for the isolation of transferrin directly from serum.
AB - A microscale procedure for the isolation of transferrin directly from human serum
(hTf) is described in this study. The protocol is based on three precipitation
steps without application of chromatography. It lasts 90min with the initial
sample volume of 250MUL. The yield of the isolated hTf is 58%, which is
considerable in biochemical terms. The purity of the isolated hTf is 97%, as
assessed by three methods: electrophoresis followed by protein staining,
immunoblotting and HPLC. Immunoblotting with antibodies against other major serum
proteins indicated that isolated hTf does not contain albumin, immunoglobulin G
or alpha-2-macroglobulin. Lectin dot-blot demonstrated that isolated hTf
preserved its glycan moieties. Fluorescent emission spectroscopy of the isolated
hTf has shown no changes in tertiary structure. Isolated hTf was approximately
26% saturated with iron ion, which is comparable to physiological value (although
a degree of saturation decreases to some extent during isolation procedure).
Finally, co-immunoprecipitation experiment confirmed that isolated hTf retained
its ligand characteristics crucial for the ligand-receptor type of interaction
with the hTf receptor. To conclude, the procedure described in this work, is time
and cost-effective, allows multiple sample handling and provides high-purity hTf
isolate with preserved structural and functional properties.
PMID- 28502561
TI - Acute hydrocephalus due to a primary malignant peripheral nerve sheath tumor of
the cervicothoracic junction: A case report and review of the literature.
AB - BACKGROUND: The estimated incidence of malignant nerve sheath tumors is 0.001%
per year, and only 2-3% of those tumors involve the spinal nerves. We present a
rare case of acute hydrocephalus caused by primary malignant peripheral nerve
sheath tumor of the cervicothoracic junction. CASE DESCRIPTION: A 29-year-old
previously healthy male patient, except for a history of two previous surgeries
for ulnar nerve entrapment and progressive left upper extremity weakness,
presented with acute onset somnolence. The CT and MRI revealed hydrocephalus and
periventricular edema. The patient underwent ventriculoperitoneal shunt surgery.
Postoperative MRI of the spine revealed a 6*3*3cm intra-extradural lesion at C7
T1 level and multiple metastases in other spinal segments. The patient underwent
combined surgical excision and the tumor was diagnosed as a malignant peripheral
nerve sheath tumor based on pathological and immunohistological findings.
Radiation therapy and chemotherapy were initiated. CONCLUSION: Primary malignant
peripheral nerve sheath tumor of the spine is a very aggressive tumor with a very
high recurrence rate, significant potential for metastasis and very poor overall
prognosis. They may present with features of more frequent diseases, such as
peripheral neuropathies and may be overlooked as in our case. Thus, suspected
cases should undergo a more detailed examination.
PMID- 28502562
TI - Grade 1 Spetzler and Martin cerebral ruptured arteriovenous malformations treated
by microsurgery: Poor functional outcome is related to injury from haemorrhage.
AB - INTRODUCTION: Ruptured arteriovenous malformations (rAVM) are life-threatening
diseases. OBJECTIVE: To evaluate the outcome of patients with grade 1 SPM rAVM
after microsurgical treatment. MATERIALS AND METHOD: We retrospectively included
64 consecutive operated patients with a grade 1 SPM rAVM in our institution
between 2002 and 2012. Complications related to the surgical procedure were
recorded. All patients were re-evaluated 3months after treatment using the
modified Rankin Scale score (mRS). Persistent neurological disorders were
evaluated 1year after bleeding. Conventional cerebral angiography was performed
for each patient immediately after surgical treatment and 1year later. RESULTS:
The mean age at diagnosis was 30.8 years. Initial WFNS score was grade 1 in 25
patients, grade 2 in 11 patients, grade 3 in 10 patients, grade 4 in 9 patients
and grade 5 in 9 patients. No remnant was left and a new surgery was performed
only in a single patient who was initially operated-on under emergency conditions
with limited preoperative investigations due to a poor clinical grade. Early
postoperative complications related to the surgical procedure were recorded in 7
patients. The mRS score 3months after treatment was <=2 in 53 patients (83%).
Persistent neurological disorders were recorded in 40 patients (62.5%). High
initial WFNS score (>2) and the hydrocephalus were significantly associated
(P<0.05) to a bad functional outcome (mRS>2). CONCLUSION: Grade 1 rAVM is a life
threatening disease concerning in most cases young patients. Long-term morbidity
is often related to the hemorrhagic brain damage and rarely to the AVM resection.
PMID- 28502563
TI - [Is the right hemisphere really minor? Involvement in the repair of bodily
injury].
AB - An appraisal mission regarding the repair of physical injury is based on the
classification of the effects of injury and scales. These scales are surprisingly
incomplete concerning the symptoms due to a right hemisphere injury. However,
these symptoms can cause an important handicap in numerous activities, social,
affective and professional. This paper reviews the recent functional anatomic
knowledge of the right hemisphere functions, visuo-spatial cognition, intentional
process and social cognition. The impacts of this appraisal data, as well as
suggestions for new scales, are outlined.
PMID- 28502564
TI - [Changes in the epidemiology of Spina Bifida in France in the last 30 years].
PMID- 28502565
TI - [Management of postoperative complications in cases of Gorham's disease with
cervical spine involvement: A case report].
AB - Gorham's disease is a rare osteolytic bone disease, caused by pathological
vascular tissue, which may spread to adjacent organs. It is a disease of unknown
etiology, primarily involving the axial skeleton and whose treatment is not
codified. Cervical spine involvement is unusual. Stabilization of the cervical
spine is a real surgical challenge. We report the case of a young adult treated
in our neurosurgery department for a cervical spine localization of Gorham's
disease.
PMID- 28502566
TI - Lateral skull base chondroblastoma resected with facial nerve posterior
transposition.
AB - INTRODUCTION: Chondroblastoma is a rare tumor that can involve the temporal bone.
Because it is a benign tumor, functional surgery must be proposed. We report a
case of a patient with a massive chondroblastoma operated on with preservation of
the facial nerve, and description of the surgical technique. CASE PRESENTATION: A
37-year-old man presented with a 9-month history of a growing left pre-auricular
mass and hearing loss. Neuroimaging showed an osteolytic mass invading the
temporal bone and temporomandibular joint. Excision was performed via a
transpetrosal and transcochlear approach with posterior transposition of the
facial nerve. EMG monitoring was effective in preventing facial palsy. Four years
later, no sign of recurrence was observed. DISCUSSION: Chondroblastoma is a
locally aggressive tumor, especially when located in the petrous bone and
temporomandibular joint. The suggested treatment is a complete excision.
PMID- 28502567
TI - Myelopathy secondary to a spinal cord compression induced by C2 nerve tumors
during head rotation.
AB - INTRODUCTION: It is well known that nerve root tumors developing in the spinal
canal can be responsible for spinal cord compression leading to myelopathy and
neurological deficits. We report the case of a patient with bilateral C2
neurofibromas presenting with a myelopathy of the upper cervical spine with no
spinal cord compression on standard magnetic resonance imaging. The spinal cord
compression occurred between the cervical neurofibromas only during head
rotation. CASE REPORT: A patient with bilateral neurofibromas of the C2 nerve
roots showed a progressive neurological deterioration with an intramedullary MRI
hypersignal without visible compression. Only an additional MRI carried-out with
the head in rotation demonstrated the tumoral dynamic compression. A review of
the literature showed that only two similar cases had previously been reported.
The largest C2 tumor was completely removed uneventfully. CONCLUSION: Dynamic
compression of the spinal cord in patients with bilateral C2 nerve root tumors
must be routinely investigated even if the standard MRI shows no compression.
PMID- 28502568
TI - Resection of cavernous angioma located in eloquent areas using functional
cortical and subcortical mapping under awake conditions. Outcomes in a 50-case
multicentre series.
AB - INTRODUCTION: Surgical resection of supratentorial cavernous angiomas located in
eloquent areas poses a significant risk to the patient of postoperative
neurological impairment and justifies intraoperative functional monitoring.
METHODS: Multicentre retrospective series of adult patients with cavernous
angiomas located within eloquent areas and treated with functional-based surgical
resection according to functional boundaries under intraoperative functional
cortico-subcortical monitoring under awake conditions. RESULTS: Fifty patients
(18 males, mean 36.3+/-10.8 year-old) underwent surgical resection with
intraoperative cortico-subcortical functional mapping using direct
electrostimulation under awake conditions for a cavernous angioma located in
eloquent areas with a mean postoperative follow-up of 21.0+/-21.2 months. At
presentation, the cavernous angioma had previously resulted in severe impairment
(neurological deficit in 34%, seizures in 70%, uncontrolled seizures in 34%,
reduced Karnofsky Performance Status score of 70 or less in 24%, inability to
work in 52%). Functional-based surgical resection allowed complete removal of the
cavernous angioma in 98% and of the haemosiderin rim in 82%. Postoperative
seizures and other complications were rare, and similarly so across all centres
included in this series. Postoperatively, we found functional improvement in 84%
of patients (reduced Karnofsky Performance Status score of 70 or less in 6%,
uncontrolled seizures in 16%, and inability to work in 11%). CONCLUSION:
Functional-based surgical resection aids the safe and complete resection of
cavernous angiomas located in eloquent areas while minimizing the surgical risks.
Functional mapping has to be considered in such challenging cases.
PMID- 28502569
TI - An In Vitro Comparison Study of the Use of a Drill or a Saw in the Hunsuck-Dal
Pont Modification of the Obwegeser Sagittal Split Osteotomy in Pig Mandibles.
AB - PURPOSE: Fracture lines in unfavorable locations are referred to as "bad splits"
in a mandibular sagittal split osteotomy (SSO). Several modifications of the
technique by Obwegeser have been introduced to minimize this risk. This in vitro
study was performed to determine whether the shape of the osteotomy cut affects
the torque and the fracture pattern of an SSO in pig mandibles. MATERIALS AND
METHODS: In a split-mouth model, 16 mandibles were split according to the Hunsuck
Dal Pont modification of the Obwegeser technique. Using an oscillating saw, sharp
edged osteotomies were created on one side of the mandible and round-edged
osteotomies were created on the contralateral side using a Lindemann bur. Torque
forces were measured during the splitting, and the lingual fracture pattern of
each split was classified. RESULTS: Torque forces were significantly (P < .05 by
paired t test) decreased by 0.77 N-m (15.6%) when a saw was used for the
osteotomy. In the 2 groups, fractures were produced along the mandibular canal.
The mandible was more often completely fractured, including the lower mandibular
border, when the fracture was created with an oscillating saw (P = .06 by Pearson
chi2 test). No correlation was found between the torque used and the fracture
pattern. CONCLUSION: Compared with round-edged osteotomies, sharp-edged
osteotomies in pig mandibles facilitated the Hunsuck-Dal Pont modification of the
Obwegeser sagittal splitting procedure and produced predictable results with
decreased torque.
PMID- 28502570
TI - A comparison of short term radiological alignment outcomes of the patient
specific and standard instrumentation for primary total knee arthroplasty: A
systematic review and meta-analysis.
AB - OBJECTIVE: The aim of this study was to review the radiological alignment
outcomes of patient Specific (PS) cutting blocks and Standard Instrumentation in
Primary Total Knee Arthroplasty. METHODS: We hypothesized that the use of PS
techniques would significantly improve sagittal, coronal and rotational alignment
of the prosthesis on short term. We performed a systematic review and a meta
analysis including all the randomised controlled trials (RCT) using PS and
standard (ST) total knee arthroplasty to date. RESULTS: A total of 538 PS TKA and
549 ST TKA were included in the study. Statistical analysis of the outliers for
femoral component sagittal, coronal and rotational positioning, tibial component
sagittal and coronal positioning and the overall mechanical axis were assessed.
We found that there was no significant benefit from using PS instrumentation in
primary knee arthroplasty to aid in the positioning of either the tibial or
femoral components. Furthermore sagittal plane tibial component positioning was
worse in the PS than the traditional ST group. CONCLUSION: Our results suggest
that at present PS instrumentation is not superior to ST instrumentation in
primary total knee arthroplasty. LEVEL OF EVIDENCE: Level 1, Systematic review of
therapeutic studies.
PMID- 28502571
TI - Opening Life's Gifts: Facing Death for a Second Time.
AB - Prior to the development of effective antiretroviral therapy, persons diagnosed
with HIV thought they were going to die. Now, long-term survivors are
contemplating death again as they age and develop other chronic diseases. The
purpose of our study was to understand the experiences of adults living with HIV
for 20 or more years as they faced death for a second time. Hermeneutic
phenomenology guided the research as participants shared their lived experience
through storytelling. Each person's story was audiotaped and transcribed
verbatim. Transcript analysis occurred as data were collected. Three common
themes from the narratives were identified: Making Choices, Transformation of
Fear, and Meaning of Death. Positive and negative pathways influenced each
participants' decision-making. Over time, fear of dying was transformed and
energy was directed toward living. Even though the participants in this study
were facing death again, they recognized it as a natural part of life.
PMID- 28502572
TI - "It Was a Learning Experience": Lessons Learned From Young African American Men
and Women's Sexual Debut.
PMID- 28502573
TI - Diverse acidogenic effluents as feedstock for microalgae cultivation: Dual phase
metabolic transition on biomass growth and lipid synthesis.
AB - In this study, a biorefinery process integrating dark fermentation with
microalgae cultivation (dual phase metabolic transition) was demonstrated with
real-field wastewater. Acid rich fermented effluents (distillery waste (FDW1);
dairy waste (FDW2)) were used as feedstock for microalgae cultivation.
Experiments were performed with FDW1 during growth phase (GP) in mixotrophic mode
and FDW2 during stress phase (SP) in both mixotrophic and heterotrophic modes.
Mixotrophic cultivation with FDW1 documented significantly higher biomass
productivity (5.3g/l). Total lipid (TL) percentage was high in mixotrophic (34%)
mode and neutral lipid (NL) was high in heterotrophic (13%) mode of cultivation
during SP with FDW2. Overall, the microalgae growth is favoured with effluents
containing high acetate, and low butyrate concentrations. Mixotrophic cultivation
enhanced both biomass growth and lipid production along with simultaneous
treatment.
PMID- 28502574
TI - DINeR: Database for Insect Neuropeptide Research.
AB - Neuropeptides are responsible for regulating a variety of functions, including
development, metabolism, water and ion homeostasis, and as neuromodulators in
circuits of the central nervous system. Numerous neuropeptides have been
identified and characterized. However, both discovery and functional
characterization of neuropeptides across the massive Class Insecta has been
sporadic. To leverage advances in post-genomic technologies for this rapidly
growing field, insect neuroendocrinology requires a consolidated, comprehensive
and standardised resource for managing neuropeptide information. The Database for
Insect Neuropeptide Research (DINeR) is a web-based database-application used for
search and retrieval of neuropeptide information of various insect species
detailing their isoform sequences, physiological functionality and images of
their receptor-binding sites, in an intuitive, accessible and user-friendly
format. The curated data includes representatives of 50 well described
neuropeptide families from over 400 different insect species. Approximately 4700
FASTA formatted, neuropeptide isoform amino acid sequences and over 200 records
of physiological functionality have been recorded based on published literature.
Also available are images of neuropeptide receptor locations. In addition, the
data include comprehensive summaries for each neuropeptide family, including
their function, location, known functionality, as well as cladograms, sequence
alignments and logos covering most insect orders. Moreover, we have adopted a
standardised nomenclature to address inconsistent classification of
neuropeptides. As part of the H2020 nEUROSTRESSPEP project, the data will be
actively maintained and curated, ensuring a comprehensive and standardised
resource for the scientific community. DINeR is publicly available at the project
website: http://www.neurostresspep.eu/diner/.
PMID- 28502575
TI - National assessment of HPV and Pap tests: Changes in cervical cancer screening,
National Health Interview Survey.
AB - BACKGROUND: Major organizations recommend cytology screening (Pap test) every
3years for women aged 21-65; women aged 30 to 65 have the option of adding the
HPV test (co-test) every 5years. We examined national percentages of cervical
cancer screening, and we examined use of co-testing as an option for screening.
METHODS: We used 2015 U.S. National Health Interview Survey (NHIS) data to
examine recent cervical cancer screening (Pap test within 3years among women aged
21-65 without a hysterectomy; N=10,596) and co-testing (N=9,125). We also
conducted a multivariable analysis to determine odds of having had a Pap test or
co-test by demographic variables. To evaluate changes in screening over time, we
examined Pap testing during the years 2000, 2005, 2008, 2010, 2013 and 2015.
Analysis completed in Atlanta, GA during 2016. RESULTS: Overall, 81.1% of
eligible women reported having a Pap test within 3years; percentages declined
over time among all age groups. An estimated 14 million women aged 21-65 had not
been screened within the past 3years. Recent immigrants to the United States,
women without insurance, and women without a usual source of healthcare had lower
odds of being up to date with screening. About 1/3 of women up to date on Pap
testing reported having a co-test with their most recent Pap test. CONCLUSIONS:
Declines in screening among women aged 21-65 are cause for concern. More research
is needed on co-testing practices. Provider and patient education efforts may be
needed to clarify recommended use of HPV tests.
PMID- 28502576
TI - The effect of MPOWER scores on cigarette smoking prevalence and consumption.
AB - BACKGROUND: The World Health Organization (WHO) introduced the MPOWER package to
support policy implementation under the Framework Convention on Tobacco Control
(FCTC). This study examined the effect of MPOWER policies on smoking prevalence
and cigarette consumption in a global context. METHODS: The MPOWER composite
score was constructed by adding up the six MPOWER scores for each country and
survey year 2007-2008, 2010, 2012, and 2014, with a possible range between 6 (1
in each of the six score) and 29 (4 in M score and 5 in POWER scores). MPOWER
composite scores that measured policy implementation were then linked to
cigarette smoking prevalence and consumption data from Euromonitor International.
Fractional logit and OLS regressions were employed to examine the effect of the
composite MPOWER score on adult smoking prevalence and cigarette consumption,
respectively. RESULTS: Results indicate that a 1-unit increase in the composite
score reduces smoking prevalence by 0.2 percentage points (p<0.05) among adults
and 0.3 percentage points (p<0.01) among adult males; and a reduction of 23
sticks of cigarette (1 pack of cigarettes) in cigarette consumption per capita
per year. At this rate, if countries had implemented the MPOWER package to the
highest levels during 2007-2014, they would have experienced a reduction in
smoking prevalence of 7.26% among adults and 7.87% among adult males and a
reduction of 13.80% in cigarette consumption. CONCLUSIONS: MPOWER policies were
effective in reducing cigarette smoking among adults. Parties should continue to
implement MPOWER policies that have been recommended by the WHO FCTC to curb
tobacco epidemic.
PMID- 28502577
TI - Psycho-social influences upon older women's decision to attend cervical
screening: A review of current evidence.
AB - Cervical cancer is the fourth most common cancer in women worldwide (WHO, 2016).
In many developed countries the incidence of cervical cancer has been
significantly reduced by the introduction of organised screening programmes
however, in the UK, a fall in screening coverage is becoming a cause for concern.
Much research attention has been afforded to younger women but age stratified
mortality and incidence data suggest that older women's screening attendance is
also worthy of study. This paper provides a review of current evidence concerning
the psycho-social influences that older women experience when deciding whether to
attend cervical screening. Few studies have focussed on older women and there are
significant methodological issues with those that have included them in their
samples. Findings from these studies indicate several barriers which may deter
older women from screening, such as embarrassment and logistical issues. Drivers
to screening include reassurance and a sense of obligation. Physical, social and
emotional changes that occur as women age may also have an impact on attendance.
This review concludes that there is a clear need for better understanding of the
perceptions of older women specifically with regard to cervical cancer and
screening. Future research should inform the design of targeted interventions and
provision of information to enable informed decision-making regarding cervical
screening among older women.
PMID- 28502578
TI - Evaluation of the expect respect support group program: A violence prevention
strategy for youth exposed to violence.
AB - In the present study, we assess the effects of the Expect Respect Support Groups
(ERSG) on frequency of teen dating violence (TDV) and general youth violence.
ERSG is a school-based violence prevention program for youth who have been
exposed to violence in their home, school, or community. Boys and girls (N=1,678,
Mage=14.3, S.D.=1.7, Range=11-17) from 36 schools in Texas participated in this
accelerated longitudinal (7-year trajectory) study beginning in 2011. Latent
growth curve analyses were conducted using three waves of data from three cross
sectional cohorts of adolescents. Among boys, the number of ERSG sessions
attended related to incremental declines in psychological TDV perpetration and
victimization, physical TDV victimization, sexual TDV perpetration and
victimization, reactive aggression, and proactive aggression. Girls attending
ERSG demonstrated reductions in reactive and proactive aggression. The present
findings suggest ERSG may be an effective cross-cutting strategy to reduce TDV
and other forms of violence among high-risk boys and possibly girls. This
information provides valuable understanding of TDV and youth violence in high
risk populations and may be useful in tailoring future prevention efforts to
different groups of teens.
PMID- 28502579
TI - Point-of-sale cigarette purchase patterns among U.S. adult smokers-National Adult
Tobacco Survey, 2012-2014.
AB - Tobacco products are ubiquitous in most U.S. retail environments. Given that data
on preferred point-of-sale purchase locations among U.S. adult tobacco users are
limited, an enhanced understanding of tobacco purchase locations can help inform
tobacco control policy, planning, and practice. We investigated prevalence and
sociodemographic characteristics associated with cigarette purchase location
among U.S. adult smokers. Pooled data came from the 2012-2013 (N=60,192) and 2013
2014 (N=75,233) National Adult Tobacco Surveys. Current cigarette smokers
(n=18,005) aged >=18 were asked if they purchased cigarettes within the previous
30days (n=15,182) and, if so, where they last purchased cigarettes. In 2016,
logistic regression adjusted for sex, age, race/ethnicity, education level and
annual household income was used to assess characteristics associated with
purchase location. Among current smokers, 90.2% reported purchasing cigarettes in
the past 30days. The most common purchase locations were convenience stores/gas
stations (69.1%), tobacco discount stores (9.9%), drug stores (5.0%),
supermarkets (4.9%), and liquor stores (3.6%). The odds of purchasing cigarettes
at convenience stores/gas stations were higher among men (adjusted odds ratio
(AOR)=1.4; 95% confidence interval (CI)=1.2-1.5) than women; and among adults
aged 18-24 (AOR=3.1; 95% CI=2.4-3.9), 25-44 (AOR=3.1; 95% CI=2.7-3.7), and 45
64years (AOR=1.8 95% CI=1.6-2.1) than adults aged >=65years. Over two-thirds of
U.S. smokers last purchased cigarettes from convenience stores/gas stations.
Understanding the relationship between purchase location and smoker
characteristics may inform tobacco control strategies in the retail environment.
PMID- 28502580
TI - [Non-antiretroviral drugs uses among HIV-infected persons receiving
antiretroviral therapy in Senegal: Costs and factors associated with
prescription].
AB - BACKGROUND: In addition to antiretroviral therapy, non-antiretroviral drugs are
necessary for the appropriate care of people living with HIV. The costs of such
drugs are totally or partially supported by the people living with HIV. We aimed
to evaluate the overall costs, the costs supported by the people living with HIV
and factors associated with the prescription of non-antiretroviral drugs in
people living with HIV on antiretroviral therapy in Senegal. METHODS: We
conducted a retrospective cohort study on 331 people living with HIV who
initiated antiretroviral therapy between 2009 and 2011 and followed until March
2012. The costs of non-antiretroviral drugs were those of the national pharmacy
for essential drugs; otherwise they were the lowest costs in the private
pharmacies. Associated factors were identified through a logistic regression
model. RESULTS: The study population was 61 % female. At baseline, 39 % of
patients were classified at WHO clinical stage 3 and 40 % at WHO clinical stage
4. Median age, body mass index and CD4 cells count were 41 years, 18kg/m2 and 93
cells/MUL, respectively. After a mean duration of 11.4 months of antiretroviral
therapy, 85 % of patients received at least one prescription for a non
antiretroviral drug. Over the entire study period, the most frequently prescribed
non-antiretroviral drugs were cotrimoxazole (78.9 % of patients), iron (33.2 %),
vitamins (21.1 %) and antibiotics (19.6 %). The mean cost per patient was 34
Euros and the mean cost supported per patient was 14 Euros. The most expensive
drugs per treated patient were antihypertensives (168 Euros), anti-ulcer agents
(12 Euros), vitamins (8.5 Euros) and antihistamines (7 Euros). The prescription
for a non-antiretroviral drug was associated with advanced clinical stage (WHO
clinical stage 3/4 versus stage 1/2): OR=2.25; 95 % CI=1.11-4.57 and viral type
(HIV-2 versus HIV-1/HIV-1+HIV-2): OR=0.36; 95 % CI=0.14-0.89. CONCLUSION: Non
antiretroviral drugs are frequently prescribed to people living with HIV in
developing countries; mainly those infected with HIV-1 and those at an advanced
clinical stage. Their costs can be a barrier to appropriate care and necessary
efforts must made to make them available. However, early initiation of
antiretroviral therapy and the registration of some non-antiretroviral drugs on
the list of essential drugs, as well as social protection systems, should reduce
their use and costs.
PMID- 28502581
TI - Human infections with avian influenza viruses in mainland China: A particular
risk for southeastern China.
PMID- 28502582
TI - Upregulation of RAD51 expression is associated with progression of thyroid
carcinoma.
AB - AIMS: RAD51 participates in homologous recombination repair (HRR) of double
stranded DNA breaks (DSBs) which may cause genomic instability and cancer. The
aim of this study was to investigate RAD51 gene expression at transcriptional and
translational levels to measure mRNA and protein level and to correlate its
relationship with proliferation marker, Ki67 in thyroid cancer patients. This
study also explored correlation of these genes with different clinicopathological
parameters of the study cohort by Spearman's rank correlation coefficient.
METHODS: Quantitative real time polymerase chain reaction (qRT-PCR) and
immunohistochemistry were used to detect mRNA transcript levels and protein
expression of RAD51 and Ki67 in 102 cases of thyroid cancer tissues and equal
number of uninvolved healthy thyroid tissue controls. RESULTS: Data showed that
expression for both RAD51 and Ki67 was significantly increased in thyroid cancer
(p<0.001). High RAD51 and Ki67 expression was associated with later stages, poor
tissue differentiation, large tumor size, positive lymph node metastasis and
distant metastasis. The correlation analysis demonstrated a strong positive
correlation (r=0.461) between RAD51 and Ki67 on mRNA level and on protein level
(r=0.866). Strong correlation was observed between clinicopathological
characteristics and selected molecules. CONCLUSION: The present study concluded
that upregulation of RAD51 and overexpression of Ki67 may be associated with the
progression of thyroid cancer.
PMID- 28502583
TI - Homozygous EDNRB mutation in a patient with Waardenburg syndrome type 1.
AB - OBJECTIVE: To examine and expand the genetic spectrum of Waardenburg syndrome
type 1 (WS1). METHODS: Clinical features related to Waardenburg syndrome (WS)
were examined in a five-year old patient. Mutation analysis of genes related to
WS was performed in the proband and her parents. Molecular modeling of EDNRB and
the p.R319W mutant was conducted to predict the pathogenicity of the mutation.
RESULTS: The proband showed sensorineural hearing loss, heterochromia iridis, and
dystopia canthorum, fulfilling the clinical criteria of WS1. Genetic analyses
revealed that the proband had no mutation in PAX3 which has been known as the
cause of WS1, but had a homozygous missense mutation (p.R319W) in endothelin
receptor type B (EDNRB) gene. The asymptomatic parents had the mutation in a
heterozygote state. This mutation has been previously reported in a heterozygous
state in a patient with Hirschsprung's disease unaccompanied by WS, but the
patient and her parents did not show any symptoms in gastrointestinal tract.
Molecular modeling of EDNRB with the p.R319W mutation demonstrated reduction of
the positively charged surface area in this region, which might reduce binding
ability of EDNRB to G protein and lead to abnormal signal transduction underlying
the WS phenotype. CONCLUSIONS: Our findings suggested that autosomal recessive
mutation in EDNRB may underlie a part of WS1 with the current diagnostic
criteria, and supported that Hirschsprung's disease is a multifactorial genetic
disease which requires additional factors. Further molecular analysis is
necessary to elucidate the gene interaction and to reappraise the current WS
classification.
PMID- 28502584
TI - Up-regulation of miR-325-3p suppresses pineal aralkylamine N-acetyltransferase
(Aanat) after neonatal hypoxia-ischemia brain injury in rats.
AB - Survivors of hypoxic-ischemic brain damage (HIBD), besides impairment of
psychomotor development, often develop circadian rhythm disorders, although the
underlying mechanisms are largely unknown. Here, we first verified that mRNA and
protein expression of pineal aralkylamine N-acetyltransferase (Aanat), a key
regulator for melatonin (MT) synthesis, along with MT, were severely impaired
after HIBD. In addition, we demonstrated that neonatal HIBD disrupted the
circadian rhythmicity of locomotor activities in juvenile rats. Based on
bioinformatics analysis of a high throughput screening of miRNA expression
changes after HIBD (Ding et al., 2015), we identified one microRNA, miR-325-3p,
as a potential candidate responsible for the down regulation of Aanat after HIBD.
Luciferase reporter assays demonstrated a specific interaction between miR-325-3p
and Aanat mRNA 3'-UTR. miR-325-3p blocked norepinephrine (NE) induced Aanat
activation in cultured pinealocytes. In addition, miR-325-3p inhibition partially
rescued Aanat induction by NE, which was significantly reduced under oxygen
glucose deprivation. By elucidating the role of pineal miR-325-3p on Aanat
expression upon injury, our study provides new insights into the
pathophysiological mechanisms of circadian dysfunction and potential therapeutic
targets after HIBD.
PMID- 28502587
TI - Direct and indirect activation of eukaryotic elongation factor 2 kinase by AMP
activated protein kinase.
AB - BACKGROUND: Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K) is a key
regulator of protein synthesis in mammalian cells. It phosphorylates and inhibits
eEF2, the translation factor necessary for peptide translocation during the
elongation phase of protein synthesis. When cellular energy demand outweighs
energy supply, AMP-activated protein kinase (AMPK) and eEF2K become activated,
leading to eEF2 phosphorylation, which reduces the rate of protein synthesis, a
process that consumes a large proportion of cellular energy under optimal
conditions. AIM: The goal of the present study was to elucidate the mechanisms by
which AMPK activation leads to increased eEF2 phosphorylation to decrease protein
synthesis. METHODS: Using genetically modified mouse embryo fibroblasts (MEFs),
effects of treatments with commonly used AMPK activators to increase eEF2
phosphorylation were compared with that of the novel compound 991. Bacterially
expressed recombinant eEF2K was phosphorylated in vitro by recombinant activated
AMPK for phosphorylation site-identification by mass spectrometry followed by
site-directed mutagenesis of the identified sites to alanine residues to study
effects on the kinetic properties of eEF2K. Wild-type eEF2K and a Ser491/Ser492
mutant were retrovirally re-introduced in eEF2K-deficient MEFs and effects of 991
treatment on eEF2 phosphorylation and protein synthesis rates were studied in
these cells. RESULTS & CONCLUSIONS: AMPK activation leads to increased eEF2
phosphorylation in MEFs mainly by direct activation of eEF2K and partly by
inhibition of mammalian target of rapamycin complex 1 (mTORC1) signaling.
Treatment of MEFs with AMPK activators can also lead to eEF2K activation
independently of AMPK probably via a rise in intracellular Ca2+. AMPK activates
eEF2K by multi-site phosphorylation and the newly identified Ser491/Ser492 is
important for activation, leading to mTOR-independent inhibition of protein
synthesis. Our study provides new insights into the control of eEF2K by AMPK,
with implications for linking metabolic stress to decreased protein synthesis to
conserve energy reserves, a pathway that is of major importance in cancer cell
survival.
PMID- 28502586
TI - Novel zinc complexes of a non-steroidal anti-inflammatory drug, niflumic acid:
Structural characterization, human-DNA and albumin binding properties.
AB - Three novel Zn(II) complexes of NSAID niflumic acid (Hnif) were prepared and
studied, namely; [Zn(MeOH)4(nif)2] (1), [Zn(cyclam)(nif)2] (2) and
[Zn(nif)2(tmen)] (3), where nif is deprotonated niflumic acid, cyclam is 1,4,8,11
Tetraazacyclotetradecane and tmen is N,N,N',N'-Tetramethylethylenediamine. The
complexes have been characterized by infrared spectroscopy, elemental and thermal
analysis and single-crystal X-ray structure analysis. All three complexes contain
two deprotonated niflumato anions monodentately coordinated via carboxylato
groups. Furthermore, fluorescence binding studies of the prepared compounds with
human genomic DNA-EB (ethidium bromide) were carried out, which suggest that all
complexes are able to bind to DNA via intercalation. Moreover, from the obtained
results it followed that complexes 2 and 3 bind to DNA from the tissue with
aortic aneurysm (aDNA) and control (cDNA) with a different strength.
Additionally, complexes 1-3 exhibit good binding affinity to human serum albumin
with high binding constant.
PMID- 28502588
TI - Alternative uses for co-products: Harnessing the potential of valuable compounds
from meat processing chains.
AB - Opportunities for exploiting the inherent value of protein-rich meat processing
co-products, in the context of increased global demand for protein and for
sustainable processing systems, are discussed. While direct consumption maybe the
most profitable route for some, this approach is influenced greatly by local and
cultural traditions. A more profitable and sustainable approach may be found in
recognizing this readily available and under-utilised resource can provide high
value components, such as proteins, with targeted high value functionality of
relevance to a variety of sectors. Applications in food & beverages, petfood
biomedical and nutrition arenas are discussed. Utilization of the raw material in
its entirety is a necessary underlying principle in this approach to help
maintain minimum waste generation. Understanding consumer attitudes to these
products, in particular when used in food or beverage systems, is critical in
optimizing commercialization strategies.
PMID- 28502589
TI - A case of a novel mutation in HNF1beta-related maturity-onset diabetes of the
young type 5 with diabetic kidney disease complication in a Chinese family.
AB - AIMS: Precise diagnosis of maturity-onset diabetes of the young (MODY) has proven
valuable for understanding mechanism of diabetes and selecting optimal therapy. A
proband and her mother with diabetic kidney disease (DKD) were studied to
investigate potential genes responsible for diabetes and different severity of
DKD between the parent and offspring. METHODS: The family with suspected MODY
underwent mutational analyses by the whole exome sequencing (WES). Candidate
pathogenic variants were validated by Sanger sequencing and tested for co
segregation. The clinical parameters of subjects were collected from medical
records. RESULTS: A novel missense heterozygous mutation in exon 4 of the
hepatocyte nuclear factor 1beta (HNF1beta), c.1007A > G (p.H336R), was identified
in both the proband and her mother. Moreover, comparing the family's WES results,
we found that the proband had acquired a KCNQ1 gene mutation from her father and
acquired ACE and SORBS1 gene mutations from her mother. These three genes are
known susceptibility genes of DKD and may impose additional effects contributing
to DKD severity. CONCLUSIONS: A novel mutation in HNF1beta-MODY was identified in
a Chinese family complicated with DKD, and the additional effect of pathogenic
variants in susceptibility genes was speculated to contribute to DKD severity.
PMID- 28502585
TI - Frontoparietal neurostimulation modulates working memory training benefits and
oscillatory synchronization.
AB - There is considerable interest in maintaining working memory (WM) because it is
essential to accomplish most cognitive tasks, and it is correlated with fluid
intelligence and ecologically valid measures of daily living. Toward this end, WM
training protocols aim to improve WM capacity and extend improvements to
unpracticed domains, yet success is limited. One emerging approach is to couple
WM training with transcranial direct current stimulation (tDCS). This pairing of
WM training with tDCS in longitudinal designs promotes behavioral improvement and
evidence of transfer of performance gains to untrained WM tasks. However, the
mechanism(s) underlying tDCS-linked training benefits remain unclear. Our goal
was to gain purchase on this question by recording high-density EEG before and
after a weeklong WM training+tDCS study. Participants completed four sessions of
frontoparietal tDCS (active anodal or sham) during which they performed a
visuospatial WM change detection task. Participants who received active anodal
tDCS demonstrated significant improvement on the WM task, unlike those who
received sham stimulation. Importantly, this pattern was mirrored by neural
correlates in spectral and phase synchrony analyses of the HD-EEG data. Notably,
the behavioral interaction was echoed by interactions in frontal-posterior alpha
band power, and theta and low alpha oscillations. These findings indicate that
one mechanism by which paired tDCS+WM training operates is to enhance cortical
efficiency and connectivity in task-relevant networks.
PMID- 28502590
TI - Spontaneous bacterial peritonitis due to Listeria monocytogenes: Always to be
remembered.
PMID- 28502592
TI - Matrix metalloproteinases as regulators of inflammatory processes.
AB - Inflammation is a central mechanism for dealing with insults to tissue, either
from pathogenic invaders or by other damage-inducing means, such that the threat
is removed, the tissue is healed and there is a return to homeostasis. It is a
multi-step process with manifold methods of regulation built in. Proteolysis is
one such regulatory method and members of the matrix metalloproteinase (MMP)
family of proteinases have been shown to influence inflammation in myriad of
ways. It is becoming more and more clear that no single MMP can be unequivocally
labeled as 'good' or 'bad' when considering inflammation in general - the net
result of proteolytic activity is dependent on context. Here we provide examples
from recent literature, with a focus on in vivo studies, to highlight this
concept. This article is part of a Special Issue entitled: Matrix
Metalloproteinases edited by Rafael Fridman.
PMID- 28502594
TI - Early evidence for a virus-like agent infecting the pest snail Theba pisana
(Gastropoda: Pulmonata) in Southern Italy.
AB - The Mediterranean land snail Theba pisana (Mollusca: Helicidae) is an introduced
agricultural pest in many countries around the world, including Australia,
Israel, USA and South Africa. In addition, this snail is an intermediate host of
parasites of importance in both human and veterinary medicine. In this study, a
natural population of T. pisana snails on the Domitian coast of Italy was
surveyed following a mass mortality event. By light microscopy, 30% of the
collected individuals showed in the calcium cells of the digestive gland the
presence of hypertrophied nuclei containing eosinophilic to weakly basophilic
inclusion bodies. Ultrastructural examination by transmission electron microscopy
(TEM) showed nuclear inclusions constituted by a reticulated stroma into which
unenveloped, roundish virus-like particles (38+/-4nm in diameter) were present.
To the best of our knowledge this could be the first evidence for a virus-like
agent infecting the gastropod T. pisana, which may open new biocontrol
perspectives of the this pest worldwide.
PMID- 28502593
TI - Meprin metalloproteases: Molecular regulation and function in inflammation and
fibrosis.
AB - The zinc-endopeptidases meprin alpha and meprin beta are extracellular proteases
involved in connective tissue homeostasis, intestinal barrier function and
immunological processes. Meprins are unique among other extracellular proteases
with regard to cleavage specificity and structure. Meprin alpha and meprin beta
have a strong preference for negatively charged amino acids around the scissile
bond, reflected by cleavage sites identified in procollagen I, the amyloid
precursor protein (APP) and the interleukin-6 receptor (IL-6R). In this review we
report on recent findings that summarize the complex molecular regulation of
meprins, particular folding, activation and shedding. Dysregulation of meprin
alpha and meprin beta is often associated with pathological conditions such as
neurodegeneration, inflammatory bowel disease and fibrosis. Based on mouse models
and patient data we suggest meprins as possible key regulators in the onset and
progression of fibrotic disorders, leading to severe diseases such as pulmonary
hypertension. This article is part of a Special Issue entitled: Proteolysis as a
Regulatory Event in Pathophysiology edited by Stefan Rose-John.
PMID- 28502591
TI - CD8+CD28+/CD8+CD28- T cell equilibrium can predict the active stage for patients
with inflammatory bowel disease.
AB - BACKGROUND/AIM: The balance of blood CD8+CD28+/CD8+CD28- T cells has been
verified to be vital for patients with ulcerative colitis (UC), but their role in
inflammatory bowel disease (IBD) remains unknown. This investigation aimed to
evaluate the efficiency of the balance in predicting the active stage in IBD
patients. METHODS: Fifty-three IBD subjects, including 31 UC and 22 Crohn's
disease (CD) patients, were enrolled, and their peripheral blood CD8+CD28+ and
CD8+CD28- T cell levels were tested using flow cytometry. The risk factors
related to prognosis were compared between UC and CD patients. A 1-year follow-up
was performed for all the IBD patients, and the CD8+ T cells and their ratio were
compared at the 3rd, 6th, 9th, and 12th months during follow-up. The sensitivity
and specificity of the CD8+ T cell level and balance were analyzed through
receiver operator characteristic (ROC) curves. The cumulative remission lasting
rates (CRLRs) under the different factors were analyzed using the Kaplan-Meier
method. RESULTS: Higher prescription rates of immunosuppressants, steroids,
probiotics, and biological agents (BAs) were found in CD subjects in comparison
to UC subjects (P=0.005, 0.024, 0.034, and 0.001), as was a higher active rate
during follow-up (95.5% of CD patients vs 67.7% of UC patients, P=0.035). The
CD8+CD28+ T cell level and the CD8+CD28+/CD8+CD28- T cell ratio were
significantly higher in UC patients than in CD patients, but the reverse was true
for CD8+CD28- T cells during follow-up at the 9th and 12th month (all P<0.05).
The diagnostic models of the initial CD8+CD28+ and CD8+CD28- T cell numbers and
the CD8+CD28+/CD8+CD28- T cell ratio in predicting the active stage were found to
be significant, with areas under the curves (AUCs) of 0.883, 0.098, and 0.913 for
UC subjects (with 95% CI: 0.709-0.940, 0.009-0.188, and 0.842-1.003; P=0.001,
0.00, and 0.000) and 0.812, 0.078, and 0.898 for CD subjects (with 95% CI: 0.683
0.957, 0.003-0.158, and 0.837-0.998; P=0.003, 0.00, and 0.000). The cut-off
values showed that when the ratios were 1.30 for UC and 1.22 for CD patients, the
best sensitivity and specificity were observed, with 91.6% and 89.0% for UC and
88.5% and 85.1% for CD, respectively. The CRLRs were significantly higher in
female, non-BA-treated, non-surgical IBD subjects when compared to male, BA
treated, surgical subjects (P=0.031, 0.000, and 0.000). The number of CD8+CD28+
and CD8+CD28- T cells and the CD8+CD28+/CD8+CD28- T cell ratio were correlated
with BA treatment and surgery (all P<0.05). CONCLUSION: The CD8+CD28+/CD8+CD28- T
cell balance, expected to be a novel immunologic marker, presented a satisfactory
efficiency with high sensitivity and specificity in predicting the active stage
in UC and CD patients, and the balance was closely related to the use of BAs and
surgery.
PMID- 28502595
TI - A sustained increase of plasma fibrinogen in sudden sensorineural hearing loss
predicts worse outcome independently.
AB - OBJECTIVES: A number of etiologies of idiopathic sudden sensorineural hearing
loss (ISSNHL) have been proposed. Vascular disturbance is one cause of ISSNHL and
has been reported to be associated with fibrinogen. We aimed to determine whether
hyperfibrinogenemia is associated with poor outcome and whether a serial change
in fibrinogen level is associated with outcome. METHODS: Twenty-two patients with
ISSNHL were enrolled. We compared the levels of fibrinogen in ISSNHL groups
classified as improved and non-improved according to improvement of hearing.
Blood samples were also collected from patients who visited the emergency room
with coronary heart disease (CHD) as the control group. RESULTS: Initial
fibrinogen level was significantly different between the non-improved and
improved ISSNHL group (350.63+/-87.20 vs. 310.71+/-81.06. The improved ISSNHL
group showed a "surge phenomenon", in which fibrinogen started to decrease at day
5 and increased at day 26. In the non-improved group, fibrinogen remained
elevated throughout the course of therapy. CONCLUSION: It is important to measure
not only the initial fibrinogen level but also to monitor its change throughout
the course of therapy in order to predict the outcome of ISSNHL.
PMID- 28502597
TI - Determining Resident Sleep During and After Call With Commercial Sleep Monitoring
Devices.
AB - OBJECTIVE: To demonstrate that commercial activity monitoring devices (CAMDs) are
practical for monitoring resident sleep while on call. Studies that have directly
monitored resident sleep are limited, likely owing to both cost and difficulty in
study interpretation. The advent of wearable CAMDs that estimate sleep presents
the opportunity to more readily evaluate resident sleep in physically active
settings and "home call," a coverage arrangement familiar to urology programs.
METHODS: Twelve urology residents were outfitted with Fitbit Flex devices during
"home call" for a total of 57 (out of 64, or 89%) call or post-call night pairs.
Residents were surveyed with the Stanford Sleepiness Scale (SSS), a single
question alertness survey. Time in bed (TIB) was "time to bed" to "rise for day."
Fitbit accelerometers register activity as follows: (1) not moving; (2) minimal
movement or restless; or (3) above threshold for accelerometer to register steps.
Total sleep time (TST) was the number of minutes in level 1 activity during TIB.
Sleep efficiency (SE) was defined as TST divided by TIB. RESULTS: While on call,
10 responding (of 12 available, 83%) residents on average reported TIB as 347
minutes, TST as 165 minutes, and had an SE of 47%. Interestingly, SSS responses
did not correlate with sleep parameters. Post-call sleep demonstrated increases
in TIB, SE, and TST (+23%, +15%, and +44%, respectively) while sleepiness was
reduced by 22%. CONCLUSION: We demonstrate that urologic residents can
consistently wear CAMDs while on home call. SSS did not correlate with Fitbit
estimated sleep duration. Further study with such devices may enhance sleep
deprivation recognition to improve resident sleep.
PMID- 28502596
TI - Safety Profile of Collagenase Clostridium Histolyticum Stratified by Degree of
Penile Curvature in Patients With Peyronie Disease.
AB - OBJECTIVE: To examine the safety of collagenase clostridium histolyticum (CCH) in
adult men with penile curvature deformity <30 degrees . CCH is indicated for
treatment of Peyronie disease in adult men with palpable plaque and a penile
curvature deformity >=30 degrees at start of therapy; however, during treatment,
patients may receive CCH injections when penile curvature deformity is <30
degrees . MATERIALS AND METHODS: Patients who received >=2 CCH treatment cycles
in 2 phase 3 studies (Investigation for Maximal Peyronie's Reduction Efficacy and
Safety Studies I and II) were included. All patients had penile curvature >=30
degrees at the beginning of treatment and could receive up to 4 treatment
cycles. The rate and number of treatment-related adverse events (TRAEs) with CCH
treatment were compared between patients with penile curvature deformity >=30
degrees and penile curvature <30 degrees . RESULTS: The number of CCH treatment
cycles included in the current analysis totaled 1204 and 289 cycles in patients
with penile curvature deformity >=30 degrees and <30 degrees , respectively. The
incidence of most TRAEs was similar between groups. Rates of penile swelling
(21.1% vs 14.5%, P = .007), penile hemorrhage (12.8% vs 8.9%; P = .046), and skin
hyperpigmentation (1.0% vs 0.1%; P = .025) were significantly higher in the <30
degrees group. The occurrence of serious TRAEs was similar between groups.
CONCLUSION: No clinically meaningful differences were observed with TRAE rates
when CCH injections were administered at penile curvature deformity >=30 degrees
vs CCH injections at penile curvature deformity <30 degrees . These findings
highlight the safety of continued CCH injections for patients who have achieved
penile curvature deformity <30 degrees after an initial treatment cycle of CCH.
PMID- 28502598
TI - Botryoid Wilms Tumor in a 2-Year-old Boy: A Case Report.
AB - We report a case of botryoid Wilms tumor that occupied the renal pelvis. A 2-year
old boy was referred to us with a chief complaint of macrohematuria.
Ultrasonography, computed tomography, and magnetic resonance imaging showed a
tumor occupying the left renal pelvis. Radical nephroureterectomy was performed.
The resected specimen showed a botryoid sarcoma-like appearance, with a pedicle
attaching to the pelvicalyceal wall, occupying the left renal pelvis. Histologic
findings confirmed botryoid Wilms tumor. Postoperative adjuvant chemotherapy was
executed. There was no recurrence or metastasis 6 months after
nephroureterectomy.
PMID- 28502599
TI - A Novel Retrieval Technique for Ureteral Stents Under Ultrasound Guidance in Male
Patients.
AB - OBJECTIVE: To simply retrieve double-J stents in male patients under ultrasound
guidance, a novel technique is developed and evaluated for efficiency, safety,
and tolerability. METHODS: Fifty-six male patients, ranging in age from 23 to 65
years old, were recruited from March to December 2015. Thirty patients (32
stents) underwent double-J stent retrieval by ultrasound guidance and 26 patients
(28 stents) underwent cystoscopy retrieval separately. Clinical outcomes were
compared between groups. Hematuria and leukocytosis were assessed every day
postoperatively. A visual analog pain scale on a scale of 0-10 was used to assess
procedure-related pain. RESULTS: In the experimental group, 87.5% of ureteral
stents were successfully removed. Using our novel technique without any local
anesthesia, male patients experienced less pain compared with the cystoscopy
group significantly (P < .001). The majority of complications were microscopic
hematuria (39.28%), less than that in the cystoscopy group (69.23%, P = .027).
Meanwhile, only few patients have leukocytosis in both groups (14.3% vs 11.5%, P
> .05). Average procedure time was 7.35 +/- 2.59 minutes longer than that of the
standard group (5.13 +/- 1.29 minutes; P < .001). However, it had been improved
with increasing experience (r = 0.618, P < .001). In addition, this novel
technique is cost-effective for clinical practice. CONCLUSION: This is the first
study to assess the possibility of ultrasound-guided retrieval technique in male
patients. The safety and success rate of this new technique is similar to that of
a conventional procedure. Whereas it is tolerable and cost effective for male and
disabled patient bear with lithotomy position.
PMID- 28502600
TI - The puzzling question of inhibitory control in Tourette syndrome: A meta
analysis.
AB - Tourette syndrome (TS) is a neuropsychiatric disorder involving motor and phonic
tics. Inhibitory control is a key issue in TS, and many disruptive or impulsive
behaviors might arise from inhibitory deficits. However, conflicting findings
regarding TS patients' inhibitory performance in neuropsychological tasks have
been reported throughout the literature. Therefore, this meta-analysis aimed to
evaluate inhibitory control through neuropsychological tasks, and to analyze the
factors modulating inhibitory deficits. To this end, a literature search was
performed through MEDLINE and PsycINFO, to retrieve studies including
neuropsychological tasks that assessed inhibitory control in TS patients. Of the
4020 studies identified, 61 were included in the meta-analysis, for a total of
1717 TS patients. Our analyses revealed a small to medium effect in favor of
inhibitory deficits in TS patients. This effect was larger in TS+ADHD patients,
but pure TS patients also showed some inhibitory deficits. Therefore, deficits in
inhibitory control seem to be an inherent component of TS, and are exacerbated
when ADHD is concomitant.
PMID- 28502601
TI - Recycling of spent lithium-ion battery with polyvinyl chloride by mechanochemical
process.
AB - In the present study, cathode materials (C/LiCoO2) of spent lithium-ion batteries
(LIBs) and waste polyvinyl chloride (PVC) were co-processed via an innovative
mechanochemical method, i.e. LiCoO2/PVC/Fe was co-grinded followed by water
leaching. This procedure generated recoverable LiCl from Li by the dechlorination
of PVC and also generated magnetic CoFe4O6 from Co. The effects of different
additives (e.g. alkali metals, non-metal oxides, and zero-valent metals) on (i)
the conversion rates of Li and Co and (ii) the dechlorination rate of PVC were
investigated, and the reaction mechanisms were explored. It was found that the
chlorine atoms in PVC were mechanochemically transformed into chloride ions that
bound to the Li in LiCoO2 to form LiCl. This resulted in reorganization of the Co
and Fe crystals to form the magnetic material CoFe4O6. This study provides a more
environmentally-friendly, economical, and straightforward approach for the
recycling of spent LIBs and waste PVC compared to traditional processes.
PMID- 28502602
TI - Uncontacted tire explosion causing trauma to bilateral lower extremities: A case
report.
AB - It is uncommon for tire explosion related injuries on the lower extremity. The
bilateral lower extremities were injured by tire explosion when the patient was
seated in a bus. She sustained an open fracture with partial bone loss in the
right calcaneus (a comminuted fracture in the right ankle joint) and a closed
comminuted fracture in the left tibia and fibula. This damage was caused by
uncontacted tire explosion, thanks to a thick floor between the exploded tire and
the patient's feet. This type of injury on lower extremity caused by uncontacted
tire explosion was uncommon.
PMID- 28502603
TI - Alcohol consumption for simulated driving performance: A systematic review.
AB - PURPOSE: Alcohol consumption can lead to risky driving and increase the frequency
of traffic accidents, injuries and mortalities. The main purpose of our study was
to compare simulated driving performance between two groups of drivers, one
consumed alcohol and the other not consumed, using a systematic review. METHODS:
In this systematic review, electronic resources and databases including Medline
via Ovid SP, EMBASE via Ovid SP, PsycINFO via Ovid SP, PubMed, Scopus, Cumulative
Index to Nursing and Allied Health Literature (CINHAL) via EBSCOhost were
comprehensively and systematically searched. The randomized controlled clinical
trials that compared simulated driving performance between two groups of drivers,
one consumed alcohol and the other not consumed, were included. Lane position
standard deviation (LPSD), mean of lane position deviation (MLPD), speed, mean of
speed deviation (MSD), standard deviation of speed deviation (SDSD), number of
accidents (NA) and line crossing (LC) were considered as the main parameters
evaluating outcomes. After title and abstract screening, the articles were
enrolled for data extraction and they were evaluated for risk of biases. RESULTS:
Thirteen papers were included in our qualitative synthesis. All included papers
were classified as high risk of biases. Alcohol consumption mostly deteriorated
the following performance outcomes in descending order: SDSD, LPSD, speed, MLPD,
LC and NA. Our systematic review had troublesome heterogeneity. CONCLUSION:
Alcohol consumption may decrease simulated driving performance in alcohol
consumed people compared with non-alcohol consumed people via changes in SDSD,
LPSD, speed, MLPD, LC and NA. More well-designed randomized controlled clinical
trials are recommended.
PMID- 28502604
TI - Death due to fracture of thin calvarial bones after a fall: A forensic approach.
AB - A 45-year-old male was autopsied. He had fallen backwards from a two-stairs
height to the ground and passed away. A skull fracture was detected in the left
occipital area, extending up to the left side of the skull base. The patient's
death occurred due to the very low thickness of the calvarial bones, which led to
the aforementioned fracture, and in turn resulted in subarachnoid hemorrhage and
death. The cortical thickness was measured and compared with average values at
standardized points. Uniform bone thinning was confirmed rather than localized.
Calvarial thinning may result from various conditions. In the present case study,
however, the exact mechanism which led to the low thickness of the calvarial
bones of the patient is undetermined. Death due to the susceptible structure and
fracture of calvarial bones has rarely been reported throughout relevant
literature.
PMID- 28502606
TI - Provider Perspectives Regarding Resuscitation Decisions for Neonates and Other
Vulnerable Patients.
AB - OBJECTIVES: To use structured surveys to assess the perspectives of pediatric
residents and neonatal nurses on resuscitation decisions for vulnerable patients,
including neonates. STUDY DESIGN: Pediatric providers were surveyed using
scenarios for 6 critically ill patients of different ages with outcomes
explicitly described. Providers were asked (1) whether resuscitation was in each
patient's best interest; (2) whether they would accept families' wishes for
comfort care (no resuscitation); and (3) to rank patients in order of priority
for resuscitation. In a structured interview, each participant explained how they
evaluated patient interests and when applicable, why their answers differed for
neonates. Interviews were audiotaped; transcripts were analyzed using thematic
analysis and mixed methods. RESULTS: Eighty pediatric residents and neonatal
nurses participated (response rate 74%). When making life and death decisions,
participants considered (1) patient characteristics (96%), (2) personal
experience/biases (85%), (3) family's wishes and desires (81%), (4) disease
characteristics (74%), and (5) societal perspectives (36%). These factors were
not in favor of sick neonates: of the participants, 85% reported having negative
biases toward neonates and 60% did not read, misinterpreted, and/or distrusted
neonatal outcome statistics. Additional factors used to justify comfort care for
neonates included limited personhood and lack of relationships/attachment (73%);
prioritization of family's best interest, and social acceptability of death
(36%). When these preconceptions were discussed, 70% of respondents reported they
would change their answers in favor of neonates. CONCLUSIONS: Resuscitation
decisions for neonates are based on many factors, such as considerations of
personhood and family's interests (that are not traditional indicators of
benefit), which may explain why decision making is different for the neonatal
population.
PMID- 28502605
TI - Transphyseal separation of the distal humerus in newborns.
AB - Obstetric traumatic separation of the distal humeral epiphysis is a very uncommon
injury, which presents a diagnostic challenge. These case serials reviewed the
functional outcomes of 5 patients who had sustained a fracture-separation of the
distal humeral epiphysis at birth. The diagnosis was made at a mean time of 40.8
h after delivery. All the patients were treated with gentle close manipulation,
reduction under fluoroscopy and above-elbow cast application. After discharge,
the patients were followed up for a mean of 30 months. Clinico-radiological
results were excellent in four patients. One case necessitated closed reduction
and percutaneous K-wire fixation at one week follow-up due to failed reduction.
Cubitusvarus deformity was the only complication noted in 1 case. Good functional
outcome can be expected in newborns with fracture-separation of the distal
humeral epiphysis wherein the physis is anatomically reduced.
PMID- 28502607
TI - Increased Serum Zonulin Levels as an Intestinal Permeability Marker in Autistic
Subjects.
AB - OBJECTIVE: To evaluate the serum levels of zonulin, which regulates tight
junctions between enterocytes and is a physiological modulator controlling
intestinal permeability, in patients with autism spectrum disorders (ASDs). STUDY
DESIGN: Serum zonulin levels were determined in 32 patients with ASD and 33
healthy controls using an enzyme-linked immunosorbent assay. The severity of ASD
symptoms was assessed with the Childhood Autism Rating Scale. RESULTS: Serum
zonulin levels were significantly higher in the patients with ASD (122.3 +/-
98.46 ng/mL) compared with the healthy controls (41.89 +/- 45.83 ng/mL). There
was a positive correlation between zonulin levels and Childhood Autism Rating
Scale score when all subjects were assessed (r = 0.523; P < .001). CONCLUSIONS:
This study suggests that zonulin, which regulates intestinal permeability, plays
a role in the development of symptoms of ASD.
PMID- 28502608
TI - The switch to infliximab biosimilars.
PMID- 28502610
TI - Functional connectivity alterations in a murine model of optic neuritis.
AB - The basis for neuronal dysfunction following inflammatory demyelination of the
central nervous system (CNS) remains poorly understood. We characterized the
network response to white matter injury in the anterior visual pathway using an
experimental model of optic neuritis (ON), as ON is often an early manifestation
of immune-mediated CNS demyelination in multiple sclerosis (MS). Optical
intrinsic signal imaging was performed before and after the induction of ON in
mice to measure changes in cortical network functional connectivity. We observed
a greater loss of connectivity between homotopic visual cortices in ON mice
compared to controls. Further, decreases in homotopic visual cortex connectivity
were associated with visual acuity loss in ON mice. These results demonstrate
that network connectivity changes resulting from ON can be modeled in an
experimental murine system. Future studies will identify the mechanisms that
cause neuronal dysfunction due to white matter injury seen in MS.
PMID- 28502609
TI - Switching from originator infliximab to biosimilar CT-P13 compared with
maintained treatment with originator infliximab (NOR-SWITCH): a 52-week,
randomised, double-blind, non-inferiority trial.
AB - BACKGROUND: TNF inhibitors have improved treatment of Crohn's disease, ulcerative
colitis, spondyloarthritis, rheumatoid arthritis, psoriatic arthritis, and
chronic plaque psoriasis, but are expensive therapies. The aim of NOR-SWITCH was
to examine switching from originator infliximab to the less expensive biosimilar
CT-P13 regarding efficacy, safety, and immunogenicity. METHODS: The study is a
randomised, non-inferiority, double-blind, phase 4 trial with 52 weeks of follow
up. Adult patients on stable treatment with infliximab originator treated in a
hospital setting for at least 6 months were eligible for participation. Patients
with informed consent were randomised in a 1:1 ratio to either continued
infliximab originator or to switch to CT-P13 treatment, with unchanged dosing
regimen. Data were collected at infusion visits in 40 Norwegian study centres.
Patients, assessors, and patient care providers were masked to treatment
allocation. The primary endpoint was disease worsening during 52-week follow-up.
394 patients in the primary per-protocol set were needed to show a non
inferiority margin of 15%, assuming 30% disease worsening in each group. This
trial is registered with ClinicalTrials.gov, number NCT02148640. FINDINGS:
Between Oct 24, 2014, and July 8, 2015, 482 patients were enrolled and randomised
(241 to infliximab originator, 241 to CT-P13 group; one patient was excluded from
the full analysis and safety set for CT-P13) and 408 were included in the per
protocol set (202 in the infliximab originator group and 206 in the CT-P13
group). 155 (32%) patients in the full analysis set had Crohn's disease, 93 (19%)
had ulcerative colitis, 91 (19%) had spondyloarthritis, 77 (16%) had rheumatoid
arthritis, 30 (6%) had psoriatic arthritis, and 35 (7%) had chronic plaque
psoriasis. Disease worsening occurred in 53 (26%) patients in the infliximab
originator group and 61 (30%) patients in the CT-P13 group (per-protocol set;
adjusted treatment difference -4.4%, 95% CI -12.7 to 3.9). The frequency of
adverse events was similar between groups (for serious adverse events, 24 [10%]
for infliximab originator vs 21 [9%] for CT-P13; for overall adverse events, 168
[70%] vs 164 [68%]; and for adverse events leading to discontinuation, nine [4%]
vs eight [3%], respectively). INTERPRETATION: The NOR-SWITCH trial showed that
switching from infliximab originator to CT-P13 was not inferior to continued
treatment with infliximab originator according to a prespecified non-inferiority
margin of 15%. The study was not powered to show non-inferiority in individual
diseases. FUNDING: Norwegian Ministry of Health and Care Services.
PMID- 28502614
TI - Partially compromised specification causes stochastic effects on gut development
in C. elegans.
AB - The C. elegans gut descends from the E progenitor cell through a series of
stereotyped cell divisions and morphogenetic events. Effects of perturbations of
upstream cell specification on downstream organogenesis have not been extensively
investigated. Here we have assembled an allelic series of strains that variably
compromise specification of E by perturbing the activation of the gut-specifying
end-1 and end-3 genes. Using a marker that allows identification of all E
descendants regardless of fate, superimposed with markers that identify cells
that have adopted a gut fate, we have examined the fate of E lineage descendants
among hundreds of embryos. We find that when specification is partially
compromised, the E lineage undergoes hyperplasia accompanied by stochastic and
variable specification of gut fate among the E descendants. As anticipated by
prior work, the activation of the gut differentiation factor elt-2 becomes
delayed in these strains, although ultimate protein levels of a translational ELT
2::GFP reporter resemble those of the wild type. By comparing these effects among
the various specification mutants, we find that the stronger the defect in
specification (i.e. the fewer number of embryos specifying gut), the stronger the
defects in the E lineage and delay in activation of elt-2. Despite the changes in
the E lineage in these strains, we find that supernumerary E descendants that
adopt a gut fate are accommodated into a relatively normal-looking intestine.
Hence, upstream perturbation of specification dramatically affects the E lineage,
but as long as sufficient descendants adopt a gut fate, organogenesis overcomes
these effects to form a relatively normal intestine.
PMID- 28502616
TI - Bilateral antegrade cerebral perfusion during aortic dissection surgery: If no
harm, then why not?
PMID- 28502615
TI - Reduce, reuse, recycle - Developmental signals in spinal cord regeneration.
AB - Anamniotes, fishes and amphibians, have the capacity to regenerate spinal cord
tissue after injury, generating new neurons that mature and integrate into the
spinal circuitry. Elucidating the molecular signals that promote this
regeneration is a fundamental question in regeneration research. Model systems,
such as salamanders and larval and adult zebrafish are used to analyse successful
regeneration. This shows that many developmental signals, such as Notch, Hedgehog
(Hh), Bone Morphogenetic Protein (BMP), Wnt, Fibroblast Growth Factor (FGF),
Retinoic Acid (RA) and neurotransmitters are redeployed during regeneration and
activate resident spinal progenitor cells. Here we compare the roles of these
signals in spinal cord development and regeneration of the much larger and fully
patterned adult spinal cord. Understanding how developmental signalling systems
are reactivated in successfully regenerating species may ultimately lead to ways
to reactivate similar systems in mammalian progenitor cells, which do not show
neurogenesis after spinal injury.
PMID- 28502613
TI - Unique patterns of organization and migration of FGF-expressing cells during
Drosophila morphogenesis.
AB - Fibroblast growth factors (FGF) are essential signaling proteins that regulate
diverse cellular functions in developmental and metabolic processes. In
Drosophila, the FGF homolog, branchless (bnl) is expressed in a dynamic and
spatiotemporally restricted pattern to induce branching morphogenesis of the
trachea, which expresses the Bnl-receptor, breathless (btl). Here we have
developed a new strategy to determine bnl- expressing cells and study their
interactions with the btl-expressing cells in the range of tissue patterning
during Drosophila development. To enable targeted gene expression specifically in
the bnl expressing cells, a new LexA based bnl enhancer trap line was generated
using CRISPR/Cas9 based genome editing. Analyses of the spatiotemporal expression
of the reporter in various embryonic stages, larval or adult tissues and in
metabolic hypoxia, confirmed its target specificity and versatility. With this
tool, new bnl expressing cells, their unique organization and functional
interactions with the btl-expressing cells were uncovered in a larval
tracheoblast niche in the leg imaginal discs, in larval photoreceptors of the
developing retina, and in the embryonic central nervous system. The targeted
expression system also facilitated live imaging of simultaneously labeled Bnl
sources and tracheal cells, which revealed a unique morphogenetic movement of the
embryonic bnl- source. Migration of bnl- expressing cells may create a dynamic
spatiotemporal pattern of the signal source necessary for the directional growth
of the tracheal branch. The genetic tool and the comprehensive profile of
expression, organization, and activity of various types of bnl-expressing cells
described in this study provided us with an important foundation for future
research investigating the mechanisms underlying Bnl signaling in tissue
morphogenesis.
PMID- 28502617
TI - Topical amiodarone: To be or not to be effective?
PMID- 28502618
TI - Training to be a thoracic surgeon: It's not idyllic, don't sugarcoat it, and
don't stop learning!
PMID- 28502619
TI - An apology or absolution for cerebral near-infrared spectroscopy: Can we get on
the same wavelength?
PMID- 28502620
TI - Discussion.
PMID- 28502621
TI - Protein-based prognostic biomarkers in lung cancer: Promise or pitfall?
PMID- 28502622
TI - How Andre Agassi helped me during my cardiothoracic surgery training.
PMID- 28502611
TI - Defining the momiome: Promiscuous information transfer by mobile mitochondria and
the mitochondrial genome.
AB - Mitochondria are complex intracellular organelles that have long been identified
as the powerhouses of eukaryotic cells because of the central role they play in
oxidative metabolism. A resurgence of interest in the study of mitochondria
during the past decade has revealed that mitochondria also play key roles in cell
signaling, proliferation, cell metabolism and cell death, and that genetic and/or
metabolic alterations in mitochondria contribute to a number of diseases,
including cancer. Mitochondria have been identified as signaling organelles,
capable of mediating bidirectional intracellular information transfer:
anterograde (from nucleus to mitochondria) and retrograde (from mitochondria to
nucleus). More recently, evidence is now building that the role of mitochondria
extends to intercellular communication as well, and that the mitochondrial genome
(mtDNA) and even whole mitochondria are indeed mobile and can mediate information
transfer between cells. We define this promiscuous information transfer function
of mitochondria and mtDNA as "momiome" to include all mobile functions of
mitochondria and the mitochondrial genome. Herein, we review the "momiome" and
explore its role in cancer development, progression, and treatment.
PMID- 28502623
TI - Documentation of vital status in the United States of America.
PMID- 28502612
TI - MARRVEL: Integration of Human and Model Organism Genetic Resources to Facilitate
Functional Annotation of the Human Genome.
AB - One major challenge encountered with interpreting human genetic variants is the
limited understanding of the functional impact of genetic alterations on
biological processes. Furthermore, there remains an unmet demand for an efficient
survey of the wealth of information on human homologs in model organisms across
numerous databases. To efficiently assess the large volume of publically
available information, it is important to provide a concise summary of the most
relevant information in a rapid user-friendly format. To this end, we created
MARRVEL (model organism aggregated resources for rare variant exploration).
MARRVEL is a publicly available website that integrates information from six
human genetic databases and seven model organism databases. For any given variant
or gene, MARRVEL displays information from OMIM, ExAC, ClinVar, Geno2MP, DGV, and
DECIPHER. Importantly, it curates model organism-specific databases to
concurrently display a concise summary regarding the human gene homologs in
budding and fission yeast, worm, fly, fish, mouse, and rat on a single webpage.
Experiment-based information on tissue expression, protein subcellular
localization, biological process, and molecular function for the human gene and
homologs in the seven model organisms are arranged into a concise output. Hence,
rather than visiting multiple separate databases for variant and gene analysis,
users can obtain important information by searching once through MARRVEL.
Altogether, MARRVEL dramatically improves efficiency and accessibility to data
collection and facilitates analysis of human genes and variants by cross
disciplinary integration of 18 million records available in public databases to
facilitate clinical diagnosis and basic research.
PMID- 28502624
TI - Prospective study of giant paraesophageal hernia repair with 1-year follow-up.
AB - OBJECTIVE: Evaluating giant paraesophageal hernia (GPEH) repair requires long
term follow-up. GPEH repair can have associated high recurrence rates, yet this
incidence depends on how recurrence is defined. Our objective was to
prospectively evaluate patients undergoing GPEH repair with 1-year follow-up.
METHODS: Patients undergoing elective GPEH repair between 2011 and 2014 were
enrolled prospectively. Postoperatively, patients were evaluated at 1 month and 1
year. Radiographic recurrence was evaluated by barium swallow and defined as a
gastroesophageal junction located above the hiatus. Quality of life was evaluated
pre- and postoperatively with the use of a validated questionnaire. RESULTS: One
hundred six patients were enrolled. The majority of GPEH repairs were performed
laparoscopically (80.2%), and 7.5% were redo repairs. At 1-year follow-up, 63.4%
of patients were symptom free, and radiographic recurrence was 32.7%. Recurrence
rate was 18.8% with standard definition (>2 cm of stomach above the diaphragm).
Quality of life scores at 1 year were significantly better after operative
repair, even in patients with radiographic recurrence (7.0 vs 22.5 all patients,
13.0 vs 22.5 with recurrence; P < .001). Patients with small radiographic
recurrences have similar satisfaction and symptom severity to patients with >2 cm
recurrences. CONCLUSIONS: GPEH repair can be performed with low operative
mortality and morbidity. The rate of recurrence at 1 year depends on the
definition used. Patient satisfaction and symptom severity are similar between
patients with radiographic and greater than 2 cm hernia recurrences. Longer
follow-up and critical assessment of our results are needed to understand the
true impact of this procedure and better inform perioperative decision making.
PMID- 28502626
TI - Organic matter in surface sediments from the Gulf of Mexico and South China Sea:
Compositions, distributions and sources.
AB - Sediments from the Gulf of Mexico (GOM) and the South China Sea (SCS) were
analyzed. The low delta13 C values of pentamethylicosane (PMIs) and fatty acids (
81.3 to -85.20/00) were found in only the S-1 sample collected from the GOM,
indicating that methanogenic archaea associated with gas hydrate formation
contributed to the sediment organic matter. Principle component analysis of fatty
acids suggested that similar microbial biomass was found in the S-1, S-9, O-3 and
O-5 samples. However, a comparison of the alkanes, fatty acids, and alcohols
indicated that the percentage of n-alkan-2-ols in the S-1 sample from the GOM was
the highest, while n-alkanes and n-fatty acids were the highest percentages in
other samples from the GOM and SCS. This finding suggests that microbial species
or the oxidation/reduction environment of the sample site of S-1 were different
from those of the other samples. The present study provides a basis for detecting
gas hydrate sites on the seafloor of the SCS.
PMID- 28502627
TI - Distribution of PBDEs, HBCDs and PCBs in the Brisbane River estuary sediment.
AB - To date, very little or no data exist in literature for some brominated flame
retardants (BFRs) and polychlorinated biphenyls in Queensland sediments. These
pollutants were measured in the sediments along the Brisbane River estuary. The
target compounds were regularly detected in measurable concentrations: PBDEs=33.3
97.8% (n=45), PCBs=94.1-100% (n=51) and HBCDs=79-98% (n=48). Consistently, >90%
of the observed ?8PBDE concentration was attributed to BDE-209. Mean PBDE levels
(ng/g dry wt.) were: 4.4+/-3.2 (?8PBDE) and 4.4+/-3.0 (BDE-209) across 22
sampling sites. The mean ?7PCB and ?HBCD were 5.4+/-4.5 and 1.0+/-1.5ng/g dry wt.
respectively. The 25% (alpha-HBCD), 8% (beta-HBCD) and 67% (gamma-HBCD)
diastereoisomer contributions observed were consistent with values reported in
the literature. Contaminant levels are fairly distributed along the River and
were generally low compared to similar studies around the world.
PMID- 28502628
TI - Magnetic fibrous sorbent for remote and efficient oil adsorption.
AB - Oil spill accident and oily water have potential risks to environment and human
health, thus need to be imperatively treated. Herein, a magnetic fibrous sorbent
was designed via electrospinning of suspension containing polymer and magnetic
nanoparticles in one step for remote and efficient oil adsorption. The morphology
of the magnetic fibrous sorbent was characterized by scanning electron
microscopy. The magnetic property and the wetting behavior were measured by
vibrating sample magnetometer and contact angle system, respectively. The results
showed that the morphology of the fibers was homogeneous and the magnetic
nanoparticles were well dispersed within the fibers. It was also found that this
composite sorbent had good magnetic response, special wettability, and remote oil
adsorption capacity. We believed this novel polymer/Fe3O4 fibrous sorbent could
be used as a promising material for the remote oil/water separation.
PMID- 28502629
TI - The inhibitory effects of levo-tetrahydropalmatine on rat Kv1.5 channels
expressed in HEK293 cells.
AB - Levo-tetrahydropalmatine (l-THP) exerts various pharmacological effects on neural
and cardiac tissues and K+ channel can be one of its multiple targets. The
rapidly activating Kv1.5 channel is expressed in a variety of tissues including
atrial cells and hippocampal neurons, and has an essential role in tuning the
action potential and excitability in those cells. The aim of current study is to
explore whether there are the possible effects of l-THP on Kv1.5 channels
expressed in HEK293 cells. Superfusion of l-THP led to a dose-dependent blockage
of Kv1.5 currents with an IC50 value of 53.2MUM. This blocking effect was
substantially attenuated in mutant H452G rather than R476V and R476Y, suggesting
a specific binding site in the outer mouth region. In addition, the properties of
Kv1.5 channel kinetics were markedly altered by l-THP. Treatment with l-THP
resulted in a potential left shift of the inactivation curve, with the half
maximum inactivation potential (V1/2) of 4.5mV in control and -12.8mV in 50MUM l
THP. Our data reveal that l-THP can exert an inhibitory effect on the delayed
rectifier Kv1.5 channels expressed in HEK293 cells. These lines of evidence
provided an insight to understand the possible effects exerted by l-THP on
relative tissues.
PMID- 28502630
TI - New opioid receptor antagonist: Naltrexone-14-O-sulfate synthesis and
pharmacology.
AB - Opioid antagonists, naloxone and naltrexone have long been used in clinical
practice and research. In addition to their low selectivity, they easily pass
through the blood-brain barrier. Quaternization of the amine group in these
molecules, (e.g. methylnaltrexone) results in negligible CNS penetration. In
addition, zwitterionic compounds have been reported to have limited CNS access.
The current study, for the first time gives report on the synthesis and the in
vitro [competition binding, G-protein activation, isolated mouse vas deferens
(MVD) and mouse colon assay] pharmacology of the zwitterionic compound,
naltrexone-14-O-sulfate. Naltrexone, naloxone, and its 14-O-sulfate analogue were
used as reference compounds. In competition binding assays, naltrexone-14-O
sulfate showed lower affinity for u, delta or kappa opioid receptor than the
parent molecule, naltrexone. However, the MU/kappa opioid receptor selectivity
ratio significantly improved, indicating better selectivity. Similar tendency was
observed for naloxone-14-O-sulfate when compared to naloxone. Naltrexone-14-O
sulfate failed to activate [35S]GTPgammaS-binding but inhibit the activation
evoked by opioid agonists (DAMGO, Ile5,6deltorphin II and U69593), similarly to
the reference compounds. Schild plot constructed in MVD revealed that naltrexone
14-O-sulfate acts as a competitive antagonist. In mouse colon, naltrexone-14-O
sulfate antagonized the inhibitory effect of morphine with lower affinity
compared to naltrexone and higher affinity when compared to naloxone or naloxone
14-O-sulfate. In vivo (mouse tail-flick test), subcutaneously injected naltrexone
14-O-sulfate antagonized morphine's antinociception in a dose-dependent manner,
indicating it's CNS penetration, which was unexpected from such zwitter ionic
structure. Future studies are needed to evaluate it's pharmacokinetic profile.
PMID- 28502631
TI - A brain-targeted ampakine compound protects against opioid-induced respiratory
depression.
AB - The use of opioid drugs for pain relief can induce life-threatening respiratory
depression. Although naloxone effectively counteracts opioid-induced respiratory
depression, it diminishes the efficacy of analgesia. Our studies indicate that
ampakines, in particular, a brain-targeted compound XD-8-17C, are able to reverse
respiratory depression without affecting analgesia at relatively low doses. Mice
and rats were subcutaneously or intravenously injected with the opioid agonist TH
030418 to induce moderate or severe respiratory depression. XD-8-17C was
intravenously administered before or after TH-030418. The effect of XD-8-17C on
opioid-induced respiratory depression was evaluated in terms of the opioid
induced acute death rate, arterial blood gas analysis and pulmonary function
tests. In addition, the hot-plate test was conducted to investigate whether XD-8
17C influenced opioid-induced analgesia. Pre-treatment with XD-8-17C
significantly reduced opioid-induced acute death, and increased the median lethal
dose of TH-030418 by 4.7-fold. Blood gas analysis and pulmonary function tests
demonstrated that post-treatment with XD-8-17C alleviated respiratory depression,
as indicated by restoration of arterial blood gas (pO2, sO2, cK+) and lung
function parameters (respiratory frequency, minute ventilation) to the normal
range. The hot-plate test showed that XD-8-17C had no impact on the
antinociceptive efficacy of morphine. The ability of XD-8-17C to reverse opioid
induced respiratory depression has the potential to increase the safety and
convenience of opioid treatment. These findings contribute to the discovery of
novel therapeutic agents that protect against opioid-induced respiratory
depression without loss of analgesia.
PMID- 28502633
TI - Remapping nociceptive stimuli into a peripersonal reference frame is spatially
locked to the stimulated limb.
AB - The localization of harmful stimuli approaching our body is essential for
survival. Here we investigated whether the mapping of nociceptive stimuli is
based on a spatial representation that is anchored to the stimulated limb. In
three experiments, we measured the effect of unilateral visual stimuli on the
perceived temporal order of nociceptive stimuli, applied to each hand. Crucially,
the position of the hands and the visual stimuli was manipulated, so that visual
and nociceptive stimuli occurred in an adjacent or non-adjacent spatial position.
Temporal order judgments of nociceptive stimuli were biased in favor of the
stimulus applied to the hand most adjacent to the visual stimulus, irrespective
to their positions in space. This suggests that the ability to determine the
position of a nociceptive stimulus on a specific body area is based on a
peripersonal representation of the stimulated limb following it during limb
displacement.
PMID- 28502634
TI - At Home in America: One Foreign Medical Graduate's View.
PMID- 28502632
TI - Two years later - Revisiting autobiographical memory representations in vmPFC and
hippocampus.
AB - A long-standing question in memory neuroscience concerns how and where
autobiographical memories of personal experiences are represented in the brain.
In a previous high resolution multivoxel pattern analysis fMRI study, we examined
two week old (recent) and ten year old (remote) autobiographical memories
(Bonnici et al., 2012, J. Neurosci. 32:16982-16991). We found that remote
memories were particularly well represented in ventromedial prefrontal cortex
(vmPFC) compared to recent memories. Moreover, while both types of memory were
represented within anterior and posterior hippocampus, remote memories were more
easily distinguished in the posterior portion. These findings suggested that a
change of some kind had occurred between two weeks and ten years in terms of
where autobiographical memories were represented in the brain. In order to
examine this further, here participants from the original study returned two
years later and recalled the memories again. We found that there was no
difference in the detectability of memory representations within vmPFC for the
now 2 year old and 12 year old memories, and this was also the case for the
posterior hippocampus. Direct comparison of the two week old memories (original
study) with themselves two years later (present study) confirmed that their
representation within vmPFC had become more evident. Overall, this within
subjects longitudinal fMRI study extends our understanding of autobiographical
memory representations by allowing us to narrow the window within which their
consolidation is likely to occur. We conclude that after a memory is initially
encoded, its representation within vmPFC has stablised by, at most, two years
later.
PMID- 28502635
TI - Identification of vitreous proteins in retinopathy of prematurity.
AB - Retinopathy of prematurity (ROP) is a disorder of blood vessels in the retina
developed in premature infants and the leading cause of the blindness in
children. Proteomic analysis was performed to identify vitreous proteins specific
to patients with ROP. Vitreous humor samples were obtained from three patients
with ROP and two patients with congenital cataract, the latter included as a
control group. The vitreous samples were separated by 2D-PAGE and the proteins
running as definitive spots were identified by MALDI-TOF MS spectrometry. We
identified 13 and 6 proteins in the vitreous from ROP and cataract patients,
respectively. Albumin, transferrin, pigment epithelium-derived factor (PEDF) and
transthyretin were found in both patient groups. In the samples from ROP
patients, PEDF and transthyretin levels were lower than in those from cataract
patients, and retinol binding protein 3 and prostaglandin D synthase were not
detected. Of the 13 proteins, 9 proteins including alpha-2-macroglobulin,
ceruloplasmin, alpha-fetoprotein, vitamin D-binding protein, alpha-1-antitrypsin,
alpha-1-beta-glycoprotein, hemopexin, apolipoprotein A-1 and A-lV were found in
vitreous samples of only the ROP patients. PEDF has anti-angiogenic and
neurotrophic functions. Whether PEDF is increased or decreased in diabetic
retinopathy has been controversial but we observed lower PEDF in the ROP samples
than in the controls. The proteins specific to or decreased in ROP, if confirmed
in future studies, may provide clue to understanding its pathogenesis.
PMID- 28502636
TI - Diabetogenic agent alloxan is a proteasome inhibitor.
AB - Alloxan has been used as a diabetogenic agent to induce diabetes. It selectively
induces pancreatic beta-cell death. The specific toxicity, however, is not fully
understood. In this study, we observed the effect of alloxan on proteasome
function. We found that alloxan caused the accumulation of ubiquitinated proteins
in NRK cells through the inhibition of the proteolytic activities of the
proteasome. Biochemistry experiments with purified 26S and 20S proteasomes
revealed that alloxan directly acts on the chymotrypsin- and trypsin-like
peptidase activities. These results demonstrate that alloxan is a proteasome
inhibitor, which suggests that its specific toxicity toward beta-cell is at least
in part through proteasome inhibition.
PMID- 28502638
TI - Oncology nurses' knowledge of guidelines for preventing catheter-related
bloodstream infections.
AB - This descriptive cross-sectional survey evaluated Jordanian oncology nurses'
knowledge of the guidelines for preventing central venous catheter-associated
infection. Poor knowledge was evident from the very low mean total scores and the
low percentage of correct answers for each item in the questionnaire.
PMID- 28502637
TI - Bathing hospitalized dependent patients with prepackaged disposable washcloths
instead of traditional bath basins: A case-crossover study.
AB - BACKGROUND: Basins used for patient bathing have been shown to be contaminated
with multidrug-resistant organisms (MDROs) and have prompted the evaluation of
alternatives to soap and water bathing methods. METHODS: We conducted a
prospective, randomized, open-label interventional crossover study to assess the
impact of replacing traditional bath basins with prepackaged washcloths on the
incidence of hospital-associated infections (HAIs), MDROs, and secondarily, rates
of skin deterioration. Unit-wide use of disposable washcloths over an 8-month
period was compared with an 8-month period of standard care using basins.
RESULTS: A total of 2,637 patients were included from 2 medical-surgical units at
a single tertiary medical center, contributing 16,034 patient days. During the
study period, there were a total of 33 unit-acquired infections, the rates of
which were not statistically different between study phases (incidence rate
ratio, 1.05; 95% confidence interval [CI], 0.50-2.23; P = .88). However,
occurrence of skin integrity deterioration was significantly less in the
intervention group (odds ratio, 0.44; 95% CI, 0.22-0.88; P = .02). CONCLUSIONS:
Although we were unable to demonstrate a significant reduction in HAI or MDRO
acquisition, we found a decrease in skin deterioration with the use of disposable
washcloths and confirmed earlier findings of MDRO contamination of wash basins.
PMID- 28502639
TI - Too much Ophthalmology? Ophthalmology in the era of over-diagnosis and over
treatment.
PMID- 28502640
TI - A cohort study reveals myocarditis to be a rare and life-threatening presentation
of large vessel vasculitis.
AB - BACKGROUND: The predominant forms of adult large vessel vasculitis (LVV) are
giant cell arteritis (GCA) and Takayasu arteritis (TA). Cardiac involvement in
LVV is a cause of morbidity and mortality, particularly in TA. Cardiac failure is
most commonly secondary to uncontrolled arterial hypertension or myocardial
ischaemia. Pulmonary hypertension and aortic valve incompetence following
ascending aortic dilatation represent other serious cardiovascular complications.
However, cardiac failure as a consequence of myocarditis is rarely reported,
principally in single case reports or in autopsy studies. METHODS: The Imperial
College LVV database was, retrospectively, reviewed to identify patients with
cardiac involvement at presentation. Patients with evidence for myocarditis were
identified. The cardiac presentation, imaging studies and subsequent medical and
surgical management were reviewed in detail. RESULTS: The cohort included 139
patients with TA and 24 with GCA. Sixteen presented with cardiac failure without
a history of ischaemic coronary heart disease, 14 (10%) with TA and 2 (8.3%) with
GCA. Cardiovascular disease identified at presentation included aortic
regurgitation (n = 11), myocarditis (n = 4) and hypertensive cardiomyopathy
secondary to renal artery stenosis (n = 1). Those patients with evidence of
myocarditis at presentation (2.8%) underwent transthoracic echocardiography and
cardiac magnetic resonance imaging (CMR). These non-invasive techniques were
sufficient for diagnosis of clinically significant myocarditis. Furthermore, they
were subsequently used to monitor response to treatment, with serial improvement
in left ventricular ejection fraction (LVEF) observed in all 4 patients (p <
0.05). Prednisolone plus cyclophosphamide (CyC) therapy was associated with
significant improvement in heart failure symptoms and LVEF in 3 cases. In one
case where CyC was contraindicated, tocilizumab treatment led to marked
improvement in cardiac symptoms. CONCLUSION: Clinically significant myocarditis
in LVV remains a rare but serious presentation. Non-invasive imaging techniques
offer an alternative to the gold-standard myocardial biopsy. Initial aggressive
immunosuppressive therapy is recommended and led to significant improvements in
LVEF and cardiac status.
PMID- 28502641
TI - Insights in luteovirid structural biology guided by chemical cross-linking and
high resolution mass spectrometry.
AB - Interactions among plant pathogenic viruses in the family Luteoviridae and their
plant hosts and insect vectors are governed by the topology of the viral capsid,
which is the sole vehicle for long distance movement of the viral genome.
Previous application of a mass spectrometry-compatible cross-linker to
preparations of the luteovirid Potato leafroll virus (PLRV; Luteoviridae:
Polerovirus) revealed a detailed network of interactions between viral structural
proteins and enabled generation of the first cross-linking guided coat protein
models. In this study, we extended application of chemical cross-linking
technology to the related Turnip yellows virus (TuYV; Luteoviridae: Polerovirus).
Remarkably, all cross-links found between sites in the viral coat protein found
for TuYV were also found in PLRV. Guided by these data, we present two models for
the TuYV coat protein trimer, the basic structural unit of luteovirid virions.
Additional cross-links found between the TuYV coat protein and a site in the
viral protease domain suggest a possible role for the luteovirid protease in
regulating the structural biology of these viruses.
PMID- 28502642
TI - Molecular detection of tick-borne pathogens in wild red foxes (Vulpes vulpes)
from Central Italy.
AB - Spleen samples from 153 red foxes, shot during regular hunting season in the
province of Pisa (Central Italy), were examined to detect DNA of Anaplasma
phagocytophilum, Ehrlichia canis, Coxiella burnetii, Francisella tularensis,
Hepatozoon canis and Babesia sp./Theileria sp. DNA of vector-borne pathogens was
detected in 120 (78.43%; 95% CI: 71.06-84.66%) foxes. Specifically, 75 (49%; 95%
CI: 40.86-57.22%) animals scored PCR-positive per H. canis, 68 (44.44%; 95% CI:
36.42-52.69%) for E. canis, 35 (22.88%; 95% CI: 16.48-30.35%) for piroplasms
(Theileria annae), 3 (1.96%; 95% CI: 0.41-5.62%) for C. burnetii and 1 (0.65%;
95% CI: 0.02-3.59%) for A. phagocytophilum. No positive reaction was observed for
F. tularensis. Fifty-six animals (36.6%; 95% CI: 28.97-44.76%) were positive for
two or three pathogens. Red foxes result to be involved in the cycle of vector
borne pathogens that are associated to disease in dogs and humans.
PMID- 28502645
TI - Elderly patients in a Mexican intensive care unit: A retrospective analysis.
PMID- 28502644
TI - Leishmania (V.) braziliensis infecting bats from Pantanal wetland, Brazil: First
records for Platyrrhinus lineatus and Artibeus planirostris.
AB - In the New World genus Leishmania parasites are etiological agents of neglected
zoonoses known as leishmaniasis. Its epidemiology is very complex due to the
participation of several species of sand fly vectors and mammalian hosts, and man
is an accidental host. Control is very difficult because of the different
epidemiological patterns of transmission observed. Studies about Leishmania spp.
infection in bats are so scarce, which represents a large gap in knowledge about
the role of these animals in the transmission cycle of these pathogens,
especially when considering that Chiroptera is one of the most abundant and
diverse orders among mammals. Leishmaniasis in Mato Grosso do Sul, Brazil are
remarkably frequent, probably due to the abundance of its regional mastofauna.
The recent record of L. braziliensis in bats from this state indicates the need
to clarify the role of these mammals in the transmission cycle. In this study we
evaluated the presence of Leishmania parasites in the skin of different species
of bats, using PCR directed to Leishmania spp. kDNA for screening followed by
PCR/RFLP analysis of the hsp70 gene for the identification of parasite species.
Leishmania species identification was confirmed by PCR directed to the G6PD gene
of L. braziliensis, followed by sequencing of the PCR product. Samples from 47
bats were processed, of which in three specimens (6.38%) was detected the
presence of Leishmania sp. kDNA. PCR/RFLP and sequencing identified the species
involved in the infection as L. braziliensis in all of them. This is the first
report of Leishmania braziliensis in bats from Pantanal ecosystem and the first
record of this species in Platyrrhinus lineatus and Artibeus planirostris, bats
with a wide distribution in South America. These results reinforce the need to
deepen the knowledge about the possibility of bats act as reservoirs of
Leishmania spp. especially considering their ability of dispersion and occupation
of anthropic environments.
PMID- 28502646
TI - Trigger reverse identification in critical care setting.
PMID- 28502643
TI - Are brucellosis, Q fever and melioidosis potential causes of febrile illness in
Madagascar?
AB - Brucellosis, Q fever and melioidosis are zoonoses, which can lead to pyrexia.
These diseases are often under-ascertained and underreported because of their
unspecific clinical signs and symptoms, insufficient awareness by physicians and
public health officers and limited diagnostic capabilities, especially in low
resource countries. Therefore, the presence of Brucella spp., Coxiella burnetii
and Burkholderia pseudomallei was investigated in Malagasy patients exhibiting
febrile illness. In addition, we analyzed zebu cattle and their ticks as
potential reservoirs for Brucella and C. burnetii, respectively. Specific
quantitative real-time PCR assays (qPCRs) were performed on 1020 blood samples
drawn from febrile patients. In total, 15 samples (1.5%) were Brucella-positive,
mainly originating from patients without travel history, while DNA from C.
burnetii and Bu. pseudomallei was not detected. Anti-C. burnetii antibodies were
found in four out of 201 zebu serum samples (2%), whereas anti-Brucella
antibodies could not be detected. Brucella DNA was detected in a single zebu
sample. Three out of 330 ticks analyzed (1%) were positively tested for C.
burnetii DNA but with high Ct values in the qPCR assay. Our data suggest that
zebus as well as Amblyomma and Boophilus ticks have to be considered as a natural
reservoir or vector for C. burnetii, but the risk of cattle-to-human transmission
is low. Since bovine brucellosis does not seem to contribute to human infections
in Madagascar, other transmission routes have to be assumed.
PMID- 28502647
TI - An accurate, specific, sensitive, high-throughput method based on a microsphere
immunoassay for multiplex detection of three viruses and bacterial fruit blotch
bacterium in cucurbits.
AB - To employ a microsphere immunoassay (MIA) to simultaneously detect multiple plant
pathogens (potyviruses, Watermelon silver mottle virus, Melon yellow spot virus,
and Acidovorax avenae subsp. citrulli) in actual plant samples, several factors
need to be optimized and rigorously validated. Here, a simple extraction method
using a single extraction buffer was successfully selected to detect the four
pathogens in various cucurbit samples (cucumber, cantaloupe, melon, and
watermelon). The extraction method and assay performance were validated with
inoculated and field cucurbit samples. The MIA showed 98-99% relative accuracy,
97-100% relative specificity and 92-100% relative sensitivity when compared to
commercial ELISA kits and reverse transcription PCR. In addition, the MIA was
also able to accurately detect multiple-infected field samples. The results
demonstrate that one common extraction method for all tested cucurbit samples
could be applied to detect multiple pathogens; avoiding the need for multiple
protocols to be employed. This multiplex method can therefore be instrumental for
high-throughput screening of multiple plant pathogens with many advantages such
as a shorter assay time (2.5h) with single assay format, a lower cost of
detection ($5 vs $19.7 for 4 pathogens/sample) and less labor requirement. Its
multiplex capacity can also be expanded to detect up to 50 different pathogens
upon the availability of specific antibodies.
PMID- 28502648
TI - Control of astrocyte morphology by Rho GTPases.
AB - Astrocytes modulate and support neuronal and synapse function via numerous
mechanisms that often rely on diffusion of signalling molecules, ions or
metabolites through extracellular space. As a consequence, the spatial
arrangement and the distance between astrocyte processes and neuronal structures
are of functional importance. Likewise, changes of astrocyte structure will
affect the ability of astrocytes to interact with neurons. In contrast to
neurons, where rapid morphology changes are critically involved in many aspects
of physiological brain function, a role of astrocyte restructuring in brain
physiology is only beginning to emerge. In neurons, small GTPases of the Rho
family are powerful initiators and modulators of structural changes. Less is
known about the functional significance of these signalling molecules in
astrocytes. Here, we review recent experimental evidence for the role of RhoA,
Cdc42 and Rac1 in controlling dynamic astrocyte morphology as well as
experimental tools and analytical approaches for studying astrocyte morphology
changes.
PMID- 28502649
TI - Post-implantation development of red-rumped agouti (Dasyprocta leporina Linnaeus,
1758).
AB - Fourteen pregnant agouti (Dasyprocta leporina Linnaeus, 1758) females at
gestational ages of 30-100days and two at gestational ages of 55-100days, were
studied, including 24 embryos/fetuses and two neonates (single offspring from two
females). Females were euthanized and embryos/fetuses were examined, measured,
and photographed. Embryos at 30days post-copulation were "C-shaped," with paddle
shaped limb buds and 10.75+/-0.11mm crown-rump length (CRL). In embryos at 35days
post-copulation, paddle-shaped forelimbs, fin-shaped pelvic limbs, and a liver
bud were evident, with 15.6+/-0.16mm CRL; at 45days, mouth and nostrils were
evident, lower incisors were emerging, and tactile hairs could be seen near the
nostrils, with 40.8+/-0.4mm CRL; at 55days, cranial sutures had fused, digits
were totally separated and claws formation was beginning, with 58.8+/-0.1mm CRL;
at 65days, the genital bud had differentiated, with 83+/-0.08mm CRL; at 85days,
the body was covered with short hair, with 127.7+/-0.6mm CRL; and at 100days, the
mature fetus had fully formed teeth and claws and an open external acoustic
meatus, with 164.3+/-10.4mm CRL. Neonates had bristly hair and open eyes, with
179.1+/-0.5mm CRL. In conclusion, characteristics of the embryo/fetus during
pregnancy can be used to estimate gestational age, and can be used as parameters
during ultrasound examinations to help identify developmental pathologies and to
test effects of nutrition, drugs, and pollution on pregnancy.
PMID- 28502650
TI - Crayfish immunity - Recent findings.
AB - Freshwater crayfish is an important commodity as well as a successful model for
studies on crustacean immunity. Due to the ease with which they are kept and the
available methods for hemocyte separation and culture they have proven to be very
useful. Here, recent progress regarding pattern recognition, immune effector
production and antiviral mechanisms are discussed. Several cases of functional
resemblance between vertebrate complement and the crayfish immune reactions are
highlighted.
PMID- 28502651
TI - RACK-1, a multifaceted regulator is required for C. elegans innate immunity
against S. flexneri M9OT infection.
AB - The nematode C. elegans has the ability to clear off bacterial colonization in
the intestine using pathogen specific innate immune response. Here, we show that
C. elegans RACK-1 has been vital in determining the survival of worms under
specific pathogenic infection. Among various pathogens tested, S. flexneri M9OT
(SF) exhibited highest pathogenicity by killing rack-1 mutant worm-VC3013 earlier
when compared to WT. The expression level of rack-1 mRNA was found to be
decreased and it further indicated that the host translational event appeared to
be affected during SF infection. Hence, inhibition of translational machinery was
the foremost reason for the early mortality in C. elegans. Apparently, variation
in the expression of RACK-1 affects the activation of p38 and JNK-MAPK pathway
which consequently triggered expression of nlp-29 and longevity, respectively.
The study unveils novel defense mechanisms exist for C. elegans in facilitating
enhanced immunity by RACK-1 against SF infection.
PMID- 28502652
TI - Comparative and evolutionary analysis of an adapter molecule MyD88 in
invertebrate metazoans.
AB - The myeloid differentiation factor 88 (MyD88) is an essential adapter in Toll
like receptor (TLR) signalling pathways, with TLR the first pattern-recognition
receptor (PRR) that was discovered in Drosophila. In the present study, a MyD88
gene was identified and characterized from a commercially important shellfish,
Scapharca subcrenata, including a DEATH domain and TIR domain conserved within
other molluscs. Furthermore, comparative genomic evidence revealed that MyD88 was
of different lengths and contained quantitative exon and intron regions, which
might be involved in specific mechanisms. To further explore the phylogenetic
relationships of invertebrate metazoan MyD88, we applied MrBayes and PhyML
software to construct phylogenetic trees using Bayesian and maximum likelihood
approaches, respectively, which suggested that the MyD88 of Arthropoda was
closely related to lower invertebrates, in contrast to morphological taxonomy.
Finally, we investigated the evolutionary patterns and location of positive
selection sites (PSSs) in the MyD88 gene from Arthropoda, Mollusca and Insecta
using PAML software with the maximum likelihood method. The data showed that
positive selection sites were detected in these groups, and partial sites were
located in the TIR domain but were not found in the DEATH domain. To summarize,
in this study, we report on the diversification of MyD88 in invertebrate
metazoans, the specific evolutionary position of Arthropoda MyD88, and the
positive selection pressures on MyD88 of Arthropoda, Mollusca and Insecta. These
results are a valuable contribution to understand and clarify the evolutionary
pattern of TLR/MyD88 signalling pathways in invertebrate and vertebrate taxa.
PMID- 28502653
TI - Heart-sparing radiotherapy in patients with breast cancer: What are the
techniques used in the clinical routine?: A pattern of practice survey in the
German-speaking countries.
AB - The aim of this study was to understand the practice of care in German-speaking
countries with regard to heart-sparing radiotherapy techniques. Between August
2015 and September 2015, an e-mail/fax-based survey was sent to radiation
oncology departments in Germany, Austria, and the German-speaking Switzerland.
The questionnaire was divided into 3 chapters: a general chapter on the
department, a chapter specific for heart-sparing techniques in patients with
breast cancer, and a third chapter on personal beliefs on the topic of heart
sparing in patients with breast cancer. A total of 82 radiation oncology
departments answered the questionnaire: 16 university clinics and 66 other
departments. In general, heart-sparing techniques are being offered by 90.2% of
departments for radiation oncology in the German-speaking countries. However, in
the clinical routine, 87.7% of institutions use heart-sparing techniques in less
than 50% of patients with breast cancer. Heart-sparing techniques are especially
provided for patients with left-sided breast cancer (80%), patients after
mastectomy (52.5%), and when the mammaria interna lymph drainage vessels are
irradiated (41.3%). In 46.3% of departments, there are written internal
guidelines for heart sparing in patients with breast cancer. Breathing-adapted
radiotherapy is used as the most frequent heart-sparing technique in 64.7% of the
institutions, followed by intensity-modulated radiation therapy, which is most
frequently used by 22.1%. The only significant difference between university
hospitals and other departments was seen for the offering of partial breast
irradiation. The most commonly used heart-sparing technique is breathing-adapted
radiotherapy, but there is no coherent approach for heart sparing in patients
with breast cancer in the German-speaking countries. Overall, all options for
cardiac protection/cardiac avoidance have their advantages and disadvantages,
with deep inspiration breath-hold radiotherapyhaving the most clear data, which
should be the preferred choice when using heart-sparing techniques.
PMID- 28502654
TI - Radiation-induced hypothyroidism in patients with breast cancer: a retrospective
analysis of 243 cases.
AB - This study aims to estimate the incidence of hypothyroidism (HT) and to evaluate
the predictors affecting the development of HT after radiotherapy (RT) for breast
cancer, with a focus on radiation dose-volumetric parameters. Between 2009 and
2015, 243 patients undergoing RT for breast cancer were retrospectively analyzed.
Free triiodothyronine (FT3), free thyroxin (FT4), and thyrotropin (TSH) were
monitored before and after RT. The relation between the doses to thyroid gland
(Dmean, Dmax, Dmin), percentage of thyroid volume receiving > 10 Gy, 20 Gy, 30
Gy, 40 Gy, and 50 Gy (V10 to V50), absolute thyroid volume, and HT were analyzed.
The risk of HT according to radiation fields and the other clinic factors were
also evaluated. The median follow-up was 41 (range; 6 to 130) months. Sixty-seven
percent of the patients received RT to the breast/chest wall and ipsilateral
supraclavicular fossa. Of 243 patients, 51 (21%) were diagnosed with HT. The
median time to the onset of HT was 27 (range; 5 to 64) months. There were no
significant relationships observed between Dmin or V10 to V50 and HT. The surgery
type, clinical stage, nodal status, RT field, Dmean, and Dmax were statistically
significant predictors for HT in univariate analysis. The Dmean was the only
prognostic factor predicting HT in multivariate analysis, and Dmean > 21 Gy was a
threshold value for the evolvement of HT. In this study, we present evidence that
postoperative irradiation of patients with breast cancer may frequently lead to
HT. Patients who have received RT for breast cancer, especially irradiation on
the supraclavicular region, may require thyroid function screening after RT.
PMID- 28502655
TI - Earliest Mysticete from the Late Eocene of Peru Sheds New Light on the Origin of
Baleen Whales.
AB - Although combined molecular and morphological analyses point to a late middle
Eocene (38-39 million years ago) origin for the clade Neoceti (Odontoceti,
echolocating toothed whales plus Mysticeti, baleen whales, and relatives), the
oldest known mysticete fossil dates from the latest Eocene (about 34 million
years ago) of Antarctica [1, 2]. Considering that the latter is not the most
stemward mysticete in recent phylogenies and that Oligocene toothed mysticetes
display a broad morphological disparity most likely corresponding to contrasted
ecological niches, the origin of mysticetes from a basilosaurid ancestor and its
drivers are currently poorly understood [1, 3-8]. Based on an articulated
cetacean skeleton from the early late Eocene (Priabonian, around 36.4 million
years ago) of the Pisco Basin, Peru, we describe a new archaic tooth-bearing
mysticete, Mystacodon selenensis gen. et sp. nov. Being the geologically oldest
neocete (crown group cetacean) and the earliest mysticete to branch off described
so far, the new taxon is interpreted as morphologically intermediate between
basilosaurids and later toothed mysticetes, providing thus crucial information
about the anatomy of the skull, forelimb, and innominate at these critical
initial stages of mysticete evolution. Major changes in the morphology of the
oral apparatus (including tooth wear) and flipper compared to basilosaurids
suggest that suction and possibly benthic feeding represented key, early
ecological traits accompanying the emergence of modern filter-feeding baleen
whales' ancestors.
PMID- 28502656
TI - Temporal Cohorts of Lineage-Related Neurons Perform Analogous Functions in
Distinct Sensorimotor Circuits.
AB - Neuronal stem cell lineages are the fundamental developmental units of the brain,
and neuronal circuits are the fundamental functional units of the brain.
Determining lineage-circuitry relationships is essential for deciphering the
developmental logic of circuit assembly. While the spatial distribution of
lineage-related neurons has been investigated in a few brain regions [1-9], an
important, but unaddressed question is whether temporal information that
diversifies neuronal progeny within a single lineage also impacts circuit
assembly. Circuits in the sensorimotor system (e.g., spinal cord) are thought to
be assembled sequentially [10-14], making this an ideal brain region for
investigating the circuit-level impact of temporal patterning within a lineage.
Here, we use intersectional genetics, optogenetics, high-throughput behavioral
analysis, single-neuron labeling, connectomics, and calcium imaging to determine
how a set of bona fide lineage-related interneurons contribute to sensorimotor
circuitry in the Drosophila larva. We show that Even-skipped lateral interneurons
(ELs) are sensory processing interneurons. Late-born ELs contribute to a
proprioceptive body posture circuit, whereas early-born ELs contribute to a
mechanosensitive escape circuit. These data support a model in which a single
neuronal stem cell can produce a large number of interneurons with similar
functional capacity that are distributed into different circuits based on birth
timing. In summary, these data establish a link between temporal specification of
neuronal identity and circuit assembly at the single-cell level.
PMID- 28502657
TI - RPL10L Is Required for Male Meiotic Division by Compensating for RPL10 during
Meiotic Sex Chromosome Inactivation in Mice.
AB - The mammalian sex chromosomes have undergone profound changes during their
evolution from an ancestral pair of autosomes [1-4]. Specifically, the X
chromosome has acquired a paradoxical sex-biased function by redistributing gene
contents [5, 6] and has generated a disproportionately high number of retrogenes
that are located on autosomes and exhibit male-biased expression patterns [6].
Several selection-based models have been proposed to explain this phenomenon,
including a model of sexual antagonism driving X inactivation (SAXI) [6-8] and a
compensatory mechanism based on meiotic sex chromosome inactivation (MSCI) [6, 8
11]. However, experimental evidence correlating the function of X-chromosome
derived autosomal retrogenes with evolutionary forces remains limited [12-17].
Here, we show that the deficiency of Rpl10l, a murine autosomal retrogene of
Rpl10 with testis-specific expression, disturbs ribosome biogenesis in late
prophase spermatocytes and prohibits the transition from prophase into metaphase
of the first meiotic division, resulting in male infertility. Rpl10l expression
compensates for the lack of Rpl10, which exhibits a broad expression pattern but
is subject to MSCI during spermatogenesis. Importantly, ectopic expression of
RPL10L prevents the death of cultured RPL10-deficient somatic cells, and Rpl10l
promoter-driven transgenic expression of Rpl10 in spermatocytes restores
spermatogenesis and fertility in Rpl10l-deficient mice. Our results demonstrate
that Rpl10l plays an essential role during the meiotic stage of spermatogenesis
by compensating for MSCI-mediated transcriptional silencing of Rpl10. These data
provide direct evidence for the compensatory hypothesis and add novel insight
into the evolution of X-chromosome-derived autosomal retrogenes and their role in
male fertility.
PMID- 28502658
TI - Spontaneous Rapid Odor Source Localization Behavior Requires Interhemispheric
Communication.
AB - Navigation, finding food sources, and avoiding danger critically depend on the
identification and spatial localization of airborne chemicals. When monitoring
the olfactory environment, rodents spontaneously engage in active olfactory
sampling behavior, also referred to as exploratory sniffing [1]. Exploratory
sniffing is characterized by stereotypical high-frequency respiration, which is
also reliably evoked by novel odorant stimuli [2, 3]. To study novelty-induced
exploratory sniffing, we developed a novel, non-contact method for measuring
respiration by infrared (IR) thermography in a behavioral paradigm in which novel
and familiar stimuli are presented to head-restrained mice. We validated the
method by simultaneously performing nasal pressure measurements, a commonly used
invasive approach [2, 4], and confirmed highly reliable detection of inhalation
onsets. We further discovered that mice actively orient their nostrils toward
novel, previously unexperienced, smells. In line with the remarkable speed of
olfactory processing reported previously [3, 5, 6], we find that mice initiate
their response already within the first sniff after odor onset. Moreover,
transecting the anterior commissure (AC) disrupted orienting, indicating that the
orienting response requires interhemispheric transfer of information. This
suggests that mice compare odorant information obtained from the two bilaterally
symmetric nostrils to locate the source of the novel odorant. We further
demonstrate that asymmetric activation of the anterior olfactory nucleus (AON) is
both necessary and sufficient for eliciting orienting responses. These findings
support the view that the AON plays an important role in the internostril
difference comparison underlying rapid odor source localization.
PMID- 28502660
TI - Beauty Requires Thought.
AB - The experience of beauty is a pleasure, but common sense and philosophy suggest
that feeling beauty differs from sensuous pleasures such as eating or sex.
Immanuel Kant [1, 2] claimed that experiencing beauty requires thought but that
sensuous pleasure can be enjoyed without thought and cannot be beautiful. These
venerable hypotheses persist in models of aesthetic processing [3-7] but have
never been tested. Here, participants continuously rated the pleasure felt from a
nominally beautiful or non-beautiful stimulus and then judged whether they had
experienced beauty. The stimuli, which engage various senses, included seeing
images, tasting candy, and touching a teddy bear. The observer reported the
feelings that the stimulus evoked. The time course of pleasure, across stimuli,
is well-fit by a model with one free parameter: pleasure amplitude. Pleasure
amplitude increases linearly with the feeling of beauty. To test Kant's claim of
a need for thought, we reduce cognitive capacity by adding a "two-back" task to
distract the observer's thoughts. The distraction greatly reduces the beauty and
pleasure experienced from stimuli that otherwise produce strong pleasure and
spares that of less-pleasant stimuli. We also find that strong pleasure is always
beautiful, whether produced reliably by beautiful stimuli or just occasionally by
sensuous stimuli. In sum, we confirm Kant's claim that only the pleasure
associated with feeling beauty requires thought and disprove his claim that
sensuous pleasures cannot be beautiful.
PMID- 28502659
TI - APC/CCdh1 Enables Removal of Shugoshin-2 from the Arms of Bivalent Chromosomes by
Moderating Cyclin-Dependent Kinase Activity.
AB - In mammalian females, germ cells remain arrested as primordial follicles.
Resumption of meiosis is heralded by germinal vesicle breakdown, condensation of
chromosomes, and their eventual alignment on metaphase plates. At the first
meiotic division, anaphase-promoting complex/cyclosome associated with Cdc20
(APC/CCdc20) activates separase and thereby destroys cohesion along chromosome
arms. Because cohesion around centromeres is protected by shugoshin-2, sister
chromatids remain attached through centromeric/pericentromeric cohesin. We show
here that, by promoting proteolysis of cyclins and Cdc25B at the germinal vesicle
(GV) stage, APC/C associated with the Cdh1 protein (APC/CCdh1) delays the
increase in Cdk1 activity, leading to germinal vesicle breakdown (GVBD). More
surprisingly, by moderating the rate at which Cdk1 is activated following GVBD,
APC/CCdh1 creates conditions necessary for the removal of shugoshin-2 from
chromosome arms by the Aurora B/C kinase, an event crucial for the efficient
resolution of chiasmata.
PMID- 28502661
TI - An Adenosine Receptor for Olfaction in Fish.
AB - Nucleotides released from food sources into environmental water are supposed to
act as feeding cues for many fish species. However, it remains unknown how fish
can sensitively detect those nucleotides. Here we discover a novel olfactory
mechanism for ATP sensing in zebrafish. Upon entering into the nostril, ATP is
efficiently converted into adenosine through enzymatic reactions of two ecto
nucleotidases expressed in the olfactory epithelium. Adenosine subsequently
activates a small population of olfactory sensory neurons expressing a novel
adenosine receptor A2c that is unique to fishes and amphibians. The information
is then transmitted to a single glomerulus in the olfactory bulb and further to
four regions in higher olfactory centers. These results provide conclusive
evidence for a sophisticated enzyme-linked receptor mechanism underlying
detection of ATP as a food-derived attractive odorant linking to foraging
behavior that is crucial and common to aquatic lower vertebrates.
PMID- 28502664
TI - The utility of susceptibility-weighted imaging to evaluate the extent of iron
accumulation in the choroid plexus of patients with beta-thalassaemia major.
AB - AIM: To assess iron accumulation in the choroid plexus of beta-thalassaemia
patients using fast spin echo (FSE) T2-weighted, gradient echo (GRE) T2*
weighted, susceptibility-weighted imaging (SWI) and compare the results.
MATERIALS AND METHODS: Eighteen patients with transfusion-dependent beta
thalassaemia and the control group underwent magnetic resonance imaging (MRI)
examinations. Signal intensities were separately evaluated using a "number of
hypointensity in the choroid plexus" (NHICP) grading system on axial FSE T2
weighted, GRE T2*-weighted, and SWI images. The NHICP grading system scores were
compared using the chi-squared test. Spearman's correlation analysis was used to
explore relationships between the variables and NHICP grading system scores.
RESULTS: The sensitivity of each technique was calculated: FSE T2-weighted
imaging=0.17, GRE T2*-weighted imaging=0.48, and SWI=0.81. Three-sample test for
equality of proportions showed that chi-squared=74.85, df=2, p<0.0001. All of the
FSE T2-weighted, GRE T2*-weighted, and SWI images differed significantly in terms
of their capacity to reveal iron accumulation in the choroid plexus. Of the three
methods, SWI was the most sensitive. CONCLUSIONS: SWI is useful for revealing
iron deposition in the brains of beta-thalassaemia patients, especially those in
the early stages of disease, and it can be used to predict disease prognosis. The
present study contributes to an understanding of the important role played by the
choroid plexus in brain iron metabolism.
PMID- 28502663
TI - Memory Reactivation Enables Long-Term Prevention of Interference.
AB - The ability of the human brain to successively learn or perform two competing
tasks constitutes a major challenge in daily function. Indeed, exposing the brain
to two different competing memories within a short temporal offset can induce
interference, resulting in deteriorated performance in at least one of the
learned memories [1-4]. Although previous studies have investigated online
interference and its effects on performance [5-13], whether the human brain can
enable long-term prevention of future interference is unknown. To address this
question, we utilized the memory reactivation-reconsolidation framework [2, 12]
stemming from studies at the synaptic level [14-17], according to which
reactivation of a memory enables its update. In a set of experiments, using the
motor sequence learning task [18] we report that a unique pairing of reactivating
the original memory (right hand) in synchrony with novel memory trials (left
hand) prevented future interference between the two memories. Strikingly, these
effects were long-term and observed a month following reactivation. Further
experiments showed that preventing future interference was not due to practice
per se, but rather specifically depended on a limited time window induced by
reactivation of the original memory. These results suggest a mechanism according
to which memory reactivation enables long-term prevention of interference,
possibly by creating an updated memory trace integrating original and novel
memories during the reconsolidation time window. The opportunity to induce a long
term preventive effect on memories may enable the utilization of strategies
optimizing normal human learning, as well as recovery following neurological
insults.
PMID- 28502662
TI - "What Not" Detectors Help the Brain See in Depth.
AB - Binocular stereopsis is one of the primary cues for three-dimensional (3D) vision
in species ranging from insects to primates. Understanding how the brain extracts
depth from two different retinal images represents a tractable challenge in
sensory neuroscience that has so far evaded full explanation. Central to current
thinking is the idea that the brain needs to identify matching features in the
two retinal images (i.e., solving the "stereoscopic correspondence problem") so
that the depth of objects in the world can be triangulated. Although intuitive,
this approach fails to account for key physiological and perceptual observations.
We show that formulating the problem to identify "correct matches" is suboptimal
and propose an alternative, based on optimal information encoding, that mixes
disparity detection with "proscription": exploiting dissimilar features to
provide evidence against unlikely interpretations. We demonstrate the role of
these "what not" responses in a neural network optimized to extract depth in
natural images. The network combines information for and against the likely depth
structure of the viewed scene, naturally reproducing key characteristics of both
neural responses and perceptual interpretations. We capture the encoding and
readout computations of the network in simple analytical form and derive a
binocular likelihood model that provides a unified account of long-standing
puzzles in 3D vision at the physiological and perceptual levels. We suggest that
marrying detection with proscription provides an effective coding strategy for
sensory estimation that may be useful for diverse feature domains (e.g., motion)
and multisensory integration.
PMID- 28502665
TI - Can the Contrast-Enhanced Ultrasound Washout Rate Be Used to Predict
Microvascular Invasion in Hepatocellular Carcinoma?
AB - The objective of this study was to investigate use of the washout rate of
hepatocellular carcinoma on contrast-enhanced ultrasound (CEUS) for pre-operative
determination of the presence of microvascular invasion. The study included 271
patients who underwent liver resection for hepatocellular carcinoma between April
2008 and December 2012, and were examined with contrast-enhanced ultrasound
before surgery. Patients were followed up at 3-mo intervals for 3 y. Four washout
patterns were classified according to the start time of washout: rapid, portal,
delayed and slow. Rapid washout, presence of two or more tumors and tumor size
>=5 cm were identified as independent pre-operative predictors of microvascular
invasion on multivariate analysis. Recurrence rates for patients with none, one,
two or three predictors were 22.6%, 34.7%, 57.6% and 75.0%, respectively. In
combination with tumor number and tumor size, contrast-enhanced ultrasound
washout rate may have a role in identifying hepatocellular carcinoma patients
with microvascular invasion.
PMID- 28502667
TI - Mechanosensitivity: From Aristotle's sense of touch to cardiac mechano-electric
coupling.
AB - Scientific interest in mechanosensation likely commenced with Aristotle's
description of the sense of touch in his treatise de Anima [On the Soul].
Considering touch as a vital sense distributed over the whole body, the
philosopher outlined a "physiological concept" at the macro-level already 2400
years ago. From this starting point, we outline the onset of modern sensory
physiology during the early 19th century. Physiologists distinguished between
outer and inner senses at that time, without, however, referring to specific
receptors or nerves. We then outline how research on four topics concerning
cardiac mechano-electric coupling developed up until the 1960's (cardio
respiratory coupling, Bainbridge reflex, Bezold-Jarisch reflex, stretch-induced
arrhythmias). Following the discovery of macroscopic phenomena (e.g. change of
heart rate, induced by atrial distension) during that period, researchers sought
to identify the pertinent receptors and reflex loops, while nowadays the
underlying subcellular mechanisms such as stretch-activated ion channels are
under investigation.
PMID- 28502666
TI - Purification and characterisation of the fission yeast Ndc80 complex.
AB - The Ndc80 complex is a conserved outer kinetochore protein complex consisting of
Ndc80 (Hec1), Nuf2, Spc24 and Spc25. This complex comprises a major, if not the
sole, platform with which the plus ends of the spindle microtubules directly
interact. In fission yeast, several studies indicate that multiple microtubule
associated proteins including the Dis1/chTOG microtubule polymerase and the
Mal3/EB1 microtubule plus-end tracking protein directly or indirectly bind Ndc80,
thereby ensuring stable kinetochore-microtubule attachment. However, the
purification of the Ndc80 complex from this yeast has not been achieved, which
hampers the in-depth investigation as to how the outer kinetochore attaches to
the plus end of the spindle microtubule. Here we report the two-step purification
of the fission yeast Ndc80 holo complex from bacteria. First, we purified
separately two sub-complexes consisting of Ndc80-Nuf2 and Spc24-Spc25. Then,
these two sub-complexes were mixed and applied to size-exclusion chromatography.
The reconstituted Ndc80 holo complex is composed of four subunits with equal
stoichiometry. The complex possesses microtubule-binding activity, and Total
Internal Reflection Fluorescence (TIRF)-microscopy assays show that the complex
binds the microtubule lattice. Interestingly, unlike the human complex, the
fission yeast complex does not track depolymerising microtubule ends. Further
analysis shows that under physiological ionic conditions, the Ndc80 holo complex
does not detectably bind Dis1, but instead it interacts with Mal3/EB1, by which
the Ndc80 complex tracks the growing microtubule plus end. This result
substantiates the notion that the Ndc80 complex plays a crucial role in
establishment of the dynamic kinetochore-microtubule interface by cooperating
with chTOG and EB1.
PMID- 28502668
TI - Spectrographic and Electroglottographic Findings of Religious Vocal Performers in
Duzce Province of Turkey.
AB - OBJECTIVES: In the present study, the register phenomenon and spectral
characteristics of vocal styles used by vocal performers in a Muslim community
were investigated. METHODS: Electroglottography was performed on 17 subjects,
whereas spectrography was performed on 18 subjects, and 16 of these subjects
participated in both parts of the study. RESULTS: We observed that the
participants used chest register in voice production and there was no change in
this situation related to the increase in frequency. It was found that Western
opera singers' formant cluster did not exist in their normal speech and
performance voice spectrum. Generally, there were clear energy peaks at the 3- to
4-kHz spectral region in their performance voice, but this peak did not appear in
the daily speech voice. CONCLUSIONS: It was concluded that a bunched F3, F4, and
F5 is a critical prerequisite in the production of a calling formant cluster.
However, it was observed that in certain cases, this phenomenon was produced only
with bunching of F4 and F5 or with an increased F4 energy level. Although an
increase in F3 assists in the production of the calling formant cluster, the main
source of the calling formant cluster was the decrease in F4 and F5 frequencies,
and the main contribution came from F5, which was fairly decreased. Moreover, it
was found that a decreased closed quotient value caused a raise in the relative
level of calling formant cluster (Lcfc) value. In conclusion, our results
indicate that the production of the calling formant cluster is based not only on
vocal tract properties but also on glottal settings.
PMID- 28502671
TI - Integrating clinical metabolomics-based biomarker discovery and clinical
pharmacology to enable precision medicine.
AB - Novel developments in biomarkers discovery are essential in modern health care,
notably in treatment individualization and precision medicine. Clinical
metabolomics, which aims to identify small molecule metabolites present in
patient-derived samples, has attracted much attention to support discovery of
novel biomarkers. However, the step from discriminatory features of disease
states towards biomarkers that can truly individualize treatments is challenging.
Biomarkers used for treatment individualization can either be dynamic or static
prognostic biomarkers. Dynamic biomarkers are relevant for describing the
clinical response, including dynamical disease progression and associated
treatment response. Static (prognostic) biomarkers do not describe but rather
predict a clinical response, and typically reflect aspects of the physiological
state of a patient related to drug treatment response or disease progression
dynamics. Pharmacokinetic-pharmacodynamic (PK-PD) modeling represents an
established approach for drug treatment individualization based on drug exposure
or treatment response biomarkers, as well as for the description of disease
progression dynamics. Here, we discuss how novel treatment individualization
biomarkers can be identified using a clinical metabolomics-based approach, and
how concepts inspired from the field of PK-PD modeling can be integrated in this
process in order to increase the clinical relevance of identified biomarkers and
precision medicine.
PMID- 28502669
TI - Biomimetic tendon extracellular matrix composite gradient scaffold enhances
ligament-to-bone junction reconstruction.
AB - : Management of ligament/tendon-to-bone-junction healing remains a formidable
challenge in the field of orthopedic medicine to date, due to deficient
vascularity and multi-tissue transitional structure of the junction. Numerous
strategies have been employed to improve ligament-bone junction healing,
including delivery of stem cells, bioactive factors, and synthetic materials, but
these methods are often inadequate at recapitulating the complex structure
function relationships at native tissue interfaces. Here, we developed an easily
fabricated and effective biomimetic composite to promote the regeneration of
ligament-bone junction by physically modifying the tendon extracellular matrix
(ECM) into a Random-Aligned-Random composite using ultrasound treatment. The
differentiation potential of rabbit bone marrow stromal cells on the modified ECM
were examined in vitro. The results demonstrated that the modified ECM enhanced
expression of chondrogenesis and osteogenesis-associated epigenetic genes
(Jmjd1c, Kdm6b), transcription factor genes (Sox9, Runx2) and extracellular
matrix genes (Col2a1, Ocn), resulting in higher osteoinductivity than the
untreated tendon ECM in vitro. In the rabbit anterior cruciate ligament (ACL)
reconstruction model in vivo, micro-computed tomography (Micro-CT) and
histological analysis showed that the modified Random-Aligned-Random composite
scaffold enhanced bone and fibrocartilage formation at the interface, more
efficaciously than the unmodified tendon ECM. Therefore, these results
demonstrated that the biomimetic Random-Aligned-Random composite could be a
promising scaffold for ligament/tendon-bone junction repair. STATEMENT OF
SIGNIFICANCE: The native transitional region consists of several distinct yet
contiguous tissue regions, composed of soft tissue, non-calcified fibrocartilage,
calcified fibrocartilage, and bone. A stratified graft whose phases are
interconnected with each other is essential for supporting the formation of
functionally continuous multi-tissue regions. Various techniques have been
attempted to improve adherence of the ligament/tendon graft to bone, including
utilization of stem cells, growth factors and biomaterials, but these methods are
often inadequate at recapitulating the complex structure-function relationships
at native tissue interfaces. Here, we developed an easily-fabricated and
effective biomimetic composite to promote the regeneration of ligament-bone
junction by physically modifying the tendon extracellular matrix (ECM) into a
Random-Aligned-Random composite using ultrasound treatment. The modified ECM
enhanced expression of chondrogenesis and osteogenesis-associated epigenetic
genes expression in vitro. In the rabbit anterior crucial ligament reconstruction
model in vivo, results showed that the modified Random-Aligned-Random composite
enhances the bone and fibrocartilage formation in the interface, proving to be
more efficient than the unmodified tendon ECM. Therefore, these results
demonstrated that the biomimetic Random-Aligned-Random composite could be a
promising scaffold for ligament/tendon-bone junction repair.
PMID- 28502670
TI - Direct quantification of dual protein adsorption dynamics in three dimensional
systems in presence of cells.
AB - : Understanding the composition of the adsorbed protein layer on a biomaterial
surface is of an extreme importance as it directs the primary biological
response. Direct detection using labeled proteins and indirect detection based on
enzymatic assays or changes to mass, refractive index or density of a surface
have been so far established. Nevertheless, using current methodologies,
detection of multiple proteins simultaneously and particularly in a three
dimensional (3D) substrates is challenging, with the exception of radiolabeling.
Here using fluorescence molecular tomography (FMT), we present a non-destructive
and versatile approach to quantify adsorption of multiple proteins within 3D
environments and reveal the dynamics of adsorption of human serum albumin (HSA)
and fibrinogen (Fib) on 3D polymeric scaffold. Furthermore, we show that serum
starved human articular chondrocytes in 3D environment preferentially uptake HSA
over Fib and to our knowledge this represents the first example of direct
visualization and quantification of protein adsorption in a 3D cell culture
system. STATEMENT OF SIGNIFICANCE: The biomaterial surface upon exposure to
biological fluids is covered by a layer of proteins, which is modified over a
period of time and dictates the fate of the biomaterial. In this study, we
present and validate a new methodology for quantification of protein adsorption
on to a three-dimensional polymer scaffold from unitary and binary systems, using
fluorescence molecular tomography, an optical trans-illumination technique with
picomolar sensitivity. In additional to being able to follow behavior of two
proteins simultaneously, this methodology is also suitable for studying protein
uptake in cells situated in a polymer environment. The ability to follow protein
adsorption/uptake in a continuous manner opens up new possibilities to study the
role of serum proteins in biomaterial compatibility.
PMID- 28502672
TI - DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel
resistance in P-glycoprotein overexpressing cancer cells.
AB - The efficacy of microtubule targeting agents in cancer treatment has been
compromised by the development of drug resistance that may involve both, P
glycoprotein overexpression and the changes in beta-tubulin isoforms' expression.
The anti-Topoisomerase II activity of methyl 4-((E)-2
(methoxycarbonyl)vinyloxy)oct-2-ynoate (DTA0100) was recently reported. Herein,
we further evaluated this propargylic enol ether derivative and found that it
exerts inhibitory effect on tubulin polymerization by binding to colchicine
binding site. DTA0100 mitotic arrest properties were investigated in two multi
drug resistant cancer cell lines with P-glycoprotein overexpression (colorectal
carcinoma and glioblastoma). The sensitivity of multi-drug resistant cancer cell
lines to DTA0100 was not significantly changed in contrast to microtubule
targeting agents such as paclitaxel, vinblastine and colchicine. DTA0100 clearly
induced microtubule depolymerization, leading to disturbance of cell cycle
kinetics and subsequent apoptosis. The fine-tuning in beta-tubulin isoforms
expression observed in multi-drug resistant cancer cells may influence the
efficacy of DTA0100. Importantly, DTA0100 blocked the P-glycoprotein function in
both multi-drug resistant cancer cell lines without inducing the increase in P
glycoprotein expression. Therefore, DTA0100 acting as dual inhibitor of
Topoisomerase II and microtubule formation could be considered as multi-potent
anticancer agent. Besides, it is able to overcome the problem of drug resistance
that emerges in the therapeutic approaches with either Topoisomerase II or
microtubule targeting agents.
PMID- 28502673
TI - Glucosamine modulates propranolol pharmacokinetics via intestinal permeability in
rats.
AB - Propranolol (PROP) undergoes extensive first-pass metabolism by the liver
resulting in a relatively low bioavailability (13-23%); thus, multiple oral doses
are required to achieve therapeutic effect. Since some studies have reported that
glucosamine (GlcN) can increase the bioavailability of some drugs, therefore, it
is aimed to study whether GlcN can change the pharmacokinetic parameters of PROP,
thus modulating its bioavailability. When PROP was orally co-administered with
GlcN (200mg/kg) to rats, PROP area under curve (AUC) and maximum concentration
(Cmax) were significantly decreased by 43% (p<0.01) and 33% (p<0.05),
respectively. In line with the in vivo results, in silico simulations confirmed
that GlcN decreased rat intestinal effective permeability (Peff) and increased
PROP clearance by 50%. However, in situ single pass intestinal perfusion (SPIP)
experiments showed that GlcN significantly increased PROP serum levels (p<0.05).
Furthermore, GlcN decreased PROP disposition/distribution into cultured
hepatocytes in concentration dependent manner. Such change in the interaction
pattern between GlcN and PROP might be attributed to the environment of the
physiological buffer used in the in vitro experiments (pH7.2) versus the oral
administration and thus, enhanced PROP permeability. Nevertheless, such
enhancement was not detected when everted gut sacks were incubated with both
drugs at the same pH in vitro. In conclusion, GlcN decreased PROP serum levels in
rats in a dose-dependent manner. Such interaction might be attributed to
decreased intestinal permeability and enhanced clearance of PROP in the presence
of GlcN. Further investigations are still warranted to explain the in vitro
inhibitory action of GlcN on PROP hepatocytes disposition and the involvement of
GlcN in the intestinal and hepatic metabolizing enzymes of PROP at different
experimental conditions.
PMID- 28502675
TI - Genotype-guided dosing of warfarin through modeling and simulation.
AB - Current genotype-guided algorithms for warfarin dosing fail to deliver optimal
performance in two aspects: 1) these algorithms are not able to achieve the same
level of benefits in non-white populations, since they were developed based on
multivariate regression analysis with mostly European/White data and did not
include genetic variants found frequently in non-white populations; 2) these
algorithms do not account for the dynamic dose/response relationship and were
limited in their usefulness to guide dosing during the initiation phase, as the
possession of variant VKORC1 and/or CYP2C9 polymorphisms has been associated with
a more rapid attainment of target international normalized ratio (INR) and higher
risk of over-anticoagulation even in genotype-guided patients. To address these
shortcomings, we report on the novel use of a previously published
kinetic/pharmacodynamic (K/PD) model to develop a warfarin dosing nomogram to be
used across genotypes and ethnicities. Our approach leverages data from both
ethnically diverse and European patients, while accounting for the differential
dose/response behaviors due to VKORC1 and CYP2C9 genotypes. According to
simulations, the utilization of our dosing nomogram could enable effective
attainment of therapeutic INR within one week in both ethnically diverse and
European populations, while maintaining uniform INR response profiles across
genotypes. Furthermore, in silico clinical trial simulations using the K/PD model
could be a feasible approach to help to further refine our dosing nomogram to be
more applicable in the clinical setting and explore possible outcomes even before
prospective clinical trials are initiated.
PMID- 28502674
TI - Evidence-based drug treatment for special patient populations through model-based
approaches.
AB - The majority of marketed drugs remain understudied in some patient populations
such as pregnant women, paediatrics, the obese, the critically-ill, and the
elderly. As a consequence, currently used dosing regimens may not assure optimal
efficacy or minimal toxicity in these patients. Given the vulnerability of some
subpopulations and the challenges and costs of performing clinical studies in
these populations, cutting-edge approaches are needed to effectively develop
evidence-based and individualized drug dosing regimens. Five key issues are
presented that are essential to support and expedite the development of drug
dosing regimens in these populations using model-based approaches: 1) model
development combined with proper validation procedures to extract as much valid
information from available study data as possible, with limited burden to
patients and costs; 2) integration of existing data and the use of prior
pharmacological and physiological knowledge in study design and data analysis, to
further develop knowledge and avoid unnecessary or unrealistic (large) studies in
vulnerable populations; 3) clinical proof-of-principle in a prospective
evaluation of a developed drug dosing regimen, to confirm that a newly proposed
regimen indeed results in the desired outcomes in terms of drug concentrations,
efficacy, and/or safety; 4) pharmacodynamics studies in addition to
pharmacokinetics studies for drugs for which a difference in disease progression
and/or in exposure-response relation is anticipated compared to the reference
population; 5) additional efforts to implement developed dosing regimens in
clinical practice once drug pharmacokinetics and pharmacodynamics have been
characterized in special patient populations. The latter remains an important
bottleneck, but this is essential to truly realize evidence-based and
individualized drug dosing for special patient populations. As all tools required
for this purpose are available, we have the moral and societal obligation to make
safe and effective pharmacotherapy available for these patients too.
PMID- 28502676
TI - The influence of drug distribution and drug-target binding on target occupancy:
The rate-limiting step approximation.
AB - The influence of drug-target binding kinetics on target occupancy can be
influenced by drug distribution and diffusion around the target, often referred
to as "rebinding" or "diffusion-limited binding". This gives rise to a decreased
decline of the drug-target complex concentration as a result of a locally higher
drug concentration that arises around the target, which leads to prolonged target
exposure to the drug. This phenomenon has been approximated by the steady-state
approximation, assuming a steady-state concentration around the target. Recently,
a rate-limiting step approximation of drug distribution and drug-target binding
has been published. However, a comparison between both approaches has not been
made so far. In this study, the rate-limiting step approximation has been
rewritten into the same mathematical format as the steady-state approximation in
order to compare the performance of both approaches for the investigation of the
influence of drug-target binding kinetics on target occupancy. While both
approximations clearly indicated the importance of kon and high target
concentrations, it was shown that the rate-limiting step approximation is more
accurate than the steady-state approximation, especially when dissociation is
fast compared to association and distribution out of the binding compartment. It
is therefore concluded that the new rate-limiting step approximation is to be
preferred for assessing the influence of binding kinetics on local target site
concentrations and target occupancy.
PMID- 28502677
TI - Biophysical study of bevacizumab structure and bioactivity under thermal and pH
stresses.
AB - The evaluation of the structural stability and bioactivity of monoclonal
antibodies (mAb) is a crucial step in the development of mAb therapeutic based
products, since immunogenicity needs to be avoided. In the present work, a study
was carried out to understand the changes on the structure and bioactivity of
mAbs induced by different pH and temperature values. Structural changes of
bevacizumab were monitored using fluorescence spectroscopy, circular dichroism
(CD) and Attenuated total reflectance-Fourier transform infrared spectroscopy
(ATR-FTIR). The secondary and tertiary structural content was monitored at six
different pH values and at room temperature, upon heating up to 85 degrees C and
upon cooling down to 20 degrees C. Furthermore, the temperature induced
conformational changes were continuously monitored from 20 degrees C to 85
degrees C using fluorescence spectroscopy and circular dichroism, allowing to
monitor the melting temperature of the protein at different pH values. The
results showed that the thermal denaturation of bevacizumab was irreversible at
all pH value. The conformational changes induced by pH were higher at extreme pH
values (5, 9 and 10) than neutral pH. Thermal stability studies showed that pH6
was the pH that confer bevacizumab the highest structural stability. These
studies were confirmed by in vitro studies, where bevacizumab's bioactivity was
measured by cell viability/proliferation at all pH values at room temperature,
and it was found a higher bioactivity for pH6. Biophysical and biological studies
were correlated in order to understand the importance of the modifications in
bevacizumab structural content on its bioactivity. However, a decrease in
bevacizumab's bioactivity was observed for pH8, 9 and 10. Overall, this work
demonstrated the usefulness of the spectroscopy techniques for estimating the
stability of therapeutic mAb during formulation development.
PMID- 28502678
TI - IL-10-producing regulatory B cells (B10 cells), IL-17+ T cells and autoantibodies
in systemic sclerosis.
AB - We aimed to analyze IL-10+ Breg (B10) cells, found to be reduced in systemic
sclerosis (SSc), in relation to SSc-specific autoAbs and IL-17+ and IFNgamma+ T
cells in SSc. Peripheral blood B10 cells from 26 patients with SSc positive for
anti-Topo I or anti-Cen autoAbs, and 12 healthy controls (HC) were studied by
flow cytometry. IL-17+ and IFNgamma+ T cells were also studied. B10 cells did not
correlate with anti-Topo I or anti-Cen Ab levels but were inversely correlated
with IL-17+ CD3+ cells and IFNgamma+ CD3+ cells. IL-17+ CD3+ cells did not
correlate with autoAb levels, but IFN-gamma+ CD3+ cells were inversely correlated
with anti-Topo I levels. In conclusion, in SSc, B10 cells did not correlate with
SSc-specific autoAbs and exhibited an inverse correlation with IL-17+ T cells and
IFNgamma+ T cells.
PMID- 28502680
TI - Semaphorin 3A: Is a key player in the pathogenesis of asthma.
AB - Immune semaphorins are key players in regulating immune mediated inflammation.
Semaphorin3A (sema3A) a secreted and membrane bound member of this family, is
well reported for its properties in maintaining self-tolerance. Semaphorin3A was
recognized to be a marker for T-regulatory cells (Tregs), and as such is a useful
tool for assessing the status of these cells in preventing immune mediated
diseases. This study was designed aiming to evaluate how sema3A is possibly
involved in bronchial asthma. Here, we found sema3A serum levels and the
expression of sema3A on Tregs significantly lower in patients with moderate to
severe asthma when compared to healthy individuals. Co-culture of condition
medium with 2mcg/ml of recombinant human sema3A with CD4+ T cells, increased the
expression of FoxP3 in Tregs, suggesting sema3A a potent immune-regulator of
inflammation including that of asthma. Further in-vivo studies will better
establish the beneficial effect of sema3A in regulating inflammation in asthma.
PMID- 28502679
TI - The association between semaphorin 3A levels and gluten-free diet in patients
with celiac disease.
AB - Celiac disease (CD) is an inflammatory disease affecting the small intestine. We
aim to assess serum level and expression of semaphorin 3A (Sema3A) on T
regulatory (Treg) cells in CD patients. Twenty-six newly diagnosed celiac
patients, 13 celiac patients on a gluten-free diet and 16 healthy controls
included in the study. Sema3A protein level in the serum of celiac patients was
significantly higher compared to healthy group (7.17+/-1.8ng/ml vs. 5.67+/
1.5ng/ml, p=0.012). Sema3A expression on Treg cells was statistically lower in
celiac patients compared to healthy subjects (p=0.009) and significantly lower in
celiac patients compared to celiac patients on gluten free diet (p=0.04).
Negative correlation was found between Sema3A on Teg cells and the level of IgA
anti-tTG antibodies (r=-0.346, p<0.01) and anti-DGP (r=-0.448, p<0.01). This
study suggests involvement of the Sema3A in the pathogenesis of CD.
PMID- 28502681
TI - Cost Implications of Primary Versus Revision Surgery in Adult Spinal Deformity.
AB - BACKGROUND: Adult spinal deformity (ASD) is an important problem to consider in
the elderly. Although studies have examined the complications of ASD surgery and
have compared functional and radiographic results of primary surgery versus
revision, no studies have compared the costs of primary procedures with
revisions. We assessed the in-hospital costs of these 2 surgery types in patients
with ASD. METHODS: The PearlDiver Database, a database of Medicare records, was
used in this study. Mutually exclusive groups of patients undergoing primary or
revision surgery were identified. Patients in each group were queried for age,
sex, and comorbidities. Thirty-day readmission rates, 30-day and 90-day
complication rates, and postoperative costs of care were assessed with
multivariate analysis. For analyses, significance was set at P < 0.001. RESULTS:
The average reimbursement of the primary surgery cohort was $57,078 +/- $30,767.
Reimbursement of revision surgery cohort was $52,999 +/- $27,658. The adjusted
difference in average costs between the 2 groups is $4773 +/- $1069 (P < 0.001).
The 30-day and 90-day adjusted difference in cost of care when sustaining any of
the major medical complications in primary surgery versus revision surgery was
insignificant. CONCLUSIONS: Patients undergoing primary and revision corrective
procedures for ASD have similar readmission rates, lengths of stays, and
complication rates. Our data showed a higher cost of primary surgery compared
with revision surgery, although costs of sustaining postoperative complications
were similar. This finding supports the decision to perform revision procedures
in patients with ASD when indicated because neither outcomes nor costs are a
hindrance to correction.
PMID- 28502682
TI - Intrarectal Anesthesia in Neurosurgery.
AB - In the early days of modern neurologic surgery, the inconveniences and potential
dangers of general anesthesia by chloroform and ether using the so-called "open
drop technique" led to the quest for alternative methods of anesthesia. This
became all the more necessary, since patient positioning and the surgical
arrangements often hindered the use of a drop bottle. One approach to solve this
problem was intrarectal ether application. The present article aims to shed light
on this original, less well-known anesthesia technique in the neurosurgical
field.
PMID- 28502683
TI - Surgical Management and Adverse Factors for Recurrence and Long-Term Survival in
Patients with Hemangiopericytoma.
AB - OBJECTIVE: Intracranial hemangiopericytoma is a rare tumor with high recurrence
rate. We analyzed adverse factors for recurrence and survival of patients with
hemangiopericytoma. METHODS: We retrospectively reviewed clinical data of 120
patients (mean age, 42 years; 60 male patients) with hemangiopericytoma who were
surgically treated in our hospital from December 2008 to January 2016. RESULTS:
Gross total resection (GTR) rate was 71.7%. Postoperative adjuvant radiotherapy
(PRT) was administered to 63 patients. After median follow-up period of 46.9
months, 35 (29.1%) recurrences and 17 (14.1%) deaths were observed. Progression
free survival (PFS) at 1, 3, and 5 years was 90.8%, 78.5%, and 68.0%, and
corresponding overall survival rate was 99.2%, 93.7%, and 82.4%. Higher
preoperative Karnofsky performance scale scores (hazard ratio [HR] = 0.896, 95%
confidence interval [CI] = 0.845-0.950, P < 0.001), convex surface location (HR =
2.151, 95% CI = 1.042-4.443, P = 0.038), and PRT (HR = 0.339, 95% CI = 0.159
0.724, P = 0.005) were independent favorable factors for PFS. For overall
survival, higher preoperative Karnofsky performance scale scores (HR = 0.914, 95%
CI = 0.854-0.978, P = 0.009), GTR (HR = 0.291, 95% CI = 0.109-0.777, P = 0.014),
and PRT (HR = 0.210, 95% CI = 0.060-0.734, P = 0.015) were independent favorable
factors. In patients undergoing non-GTR, PRT significantly improved PFS (HR =
0.252, 95% CI = 0.070-0.906, P = 0.035). CONCLUSIONS: This study revealed risk
factors for PFS and overall survival to predict outcomes and determine
treatments. GTR was attempted as frequently as possible, and PRT was recommended
for patients with non-GTR or recurrence to improve tumor control.
PMID- 28502684
TI - Metastatic Neuroendocrine Carcinoma of Unknown Origin Arising in the Femoral
Nerve Sheath.
AB - BACKGROUND: Metastatic neuroendocrine carcinoma of unknown origin is a rare
condition, usually presenting with lesions in the liver and/or lung. We present
the first reported case of a metastatic neuroendocrine carcinoma of unknown
origin arising in the femoral nerve sheath. CASE DESCRIPTION: Magnetic resonance
imaging demonstrated what was thought to be a schwannoma in the left femoral
nerve sheath in the proximal femoral triangle, immediately inferior to the
anterior inferior iliac spine. At the time of operation, the tumor capsule was
invading surrounding tissue, as well as three trunks of the femoral nerve. The
patient underwent a subtotal resection, preserving the integrity of the residual
functioning femoral nerve trunks. Histologic evaluation determined that the tumor
had features consistent with a metastatic neuroendocrine carcinoma of unknown
primary origin. The patient recovered well postoperatively, and subsequent
radiologic evaluation failed to demonstrate a potential primary site.
Unfortunately, the patient re-presented with disease progression and was
subsequently referred to palliative care. CONCLUSIONS: We recommend that there is
a definite role for surgery in the management of solitary neuroendocrine
carcinoma of unknown origin.
PMID- 28502685
TI - Transorbital Glue Embolization of a Recurrent Venous Varix Using Real-Time Image
Guidance in the Neuroangiography Suite.
AB - Orbital lesions are challenging to access due to their location amid critical
anatomic structures. Here, we demonstrate direct transorbital cannulation of an
orbital venous varix using image guidance. A 36-year-old male was diagnosed with
a left orbital venous varix approximately 5 years ago at an outside institution.
He subsequently underwent surgery for direct intraoperative embolization of the
venous varix followed by surgical resection. The patient recently presented to us
with left eye pain, proptosis, double vision, and conjunctival hemorrhage
precipitated by straining or lying flat. Orbital magnetic resonance imaging
showed recurrence of the venous varix, which was then confirmed with digital
subtraction angiography and intraprocedural computed tomography (DynaCT, Siemens
Healthineers, Erlangen, Germany). Due to scarring from the previous surgery,
percutaneous transorbital embolization of the venous varix was planned. The
needle trajectory was determined and also visualized in real-time using image
guidance (Needle Guidance, Siemens Healthineers). Once the needle reached the
desired target, n-butyl cyanoacrylate glue (Codman Neuro, San Jose, California)
was injected until nearly the entire venous varix was occluded. There were no
complications, and at his postoperative visit the patient reported resolution of
all symptoms.
PMID- 28502686
TI - Customized Polymethylmethacrylate Cranioplasty Implants Using 3-Dimensional
Printed Polylactic Acid Molds: Technical Note with 2 Illustrative Cases.
AB - OBJECTIVES: Prefabricated customized cranioplasty implants are anatomically more
accurate than manually shaped acrylic implants but remain costly. The authors
describe a new cost-effective technique of producing customized
polymethylmethacrylate (PMMA) cranioplasty implants with the use of prefabricated
3-dimensional (3D) printed molds. METHODS: The first patient had a left frontal
cranial defect after a craniotomy for a glial tumor. A 3D image of his skull was
obtained from axial 0.6-mm computed tomography (CT) scan images. The image of the
implant was generated by a digital subtraction mirror-imaging process using the
normal side of his cranium as a model. The second patient had a bifrontal defect
after the resection of an infected customized polyetheretherketone implant. A 3D
image of the infected implant was directly obtained from an axial 0.6-mm CT scan
before discarding it. The images were then used to produce for each patient a
mold of the external surface of the cranium using a low-cost polylactic acid 3D
printer. Intraoperatively, each mold was put in a sterile bag and then used to
cast a customized PMMA implant subsequently trimmed before fixation. RESULTS:
Both patients had excellent cosmetic results and underwent postoperative CT scans
that showed excellent restoration of the symmetrical contours of the cranium. No
neurologic or infectious complications occurred over a 6-month follow-up for
either patient. CONCLUSIONS: Making customized PMMA cranioplasty implants via 3D
printed polylactic acid molds is a cost-effective technique for delayed
reconstruction of various cranial defects.
PMID- 28502687
TI - The Onodi Cell: An Anatomic Illustration.
AB - This anatomic image demonstrates the sphenoethmoidal (Onodi) cell (a variant of
the paranasal sinuses), the identification of which is critical to prevent
neurovascular injury during endoscopic approaches to the sella and adjacent
regions of the skull base.
PMID- 28502688
TI - Evaluating Outcomes of Stand-Alone Anterior Lumbar Interbody Fusion: A Systematic
Review.
AB - BACKGROUND: Stand-alone anterior lumbar interbody fusion (ALIF) is an effective
surgical approach for selected spinal pathologies. It avoids the morbidity and
complications associated with instrumented ALIF, such as plate fixation and the
traditionally used posterior approach. Despite improved disc space visualization
and clearance, the associated posterior instability and increased risk of
nonfusion present major challenges to this approach. The integral cage design
aims to address these challenges by providing the necessary stabilization through
intracorporeal screws. However, there is limited and controversial data available
for stand-alone ALIF and integral cage fixation. To our knowledge, this is the
first systematic review to evaluate recent findings on outcomes of stand-alone
ALIF devices to explore areas of controversy and identify directions for future
research. METHODS: Two reviewers conducted independent, systematic literature
searches for appropriate studies in 5 electronic databases as per Preferred
Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were
filtered by the use of specified selection criteria, particularly exclusion of
studies with supplementary fixation to ALIF and studies published before the year
2000. A total of 17 studies met the criteria, and their data were comprehensively
extracted and analyzed. RESULTS: The current literature is supportive of stand
alone ALIF due to acceptable clinical outcomes, promising fusion rates and disc
height restoration. However, data and outcomes remain preliminary, and there are
numerous areas of controversy. CONCLUSIONS: There is evidence for the efficacy
and safety of stand-alone ALIF. However, the extent of improvement based on
specific indications for surgery remains unclear. Further investigation utilizing
more methodologically rigorous studies of long-term outcomes is necessary to
address these issues.
PMID- 28502689
TI - Complicated Mild Traumatic Brain Injury and the Need for Imaging Surveillance.
AB - OBJECTIVE: To evaluate the need for repeat head computed tomography (CT) in
patients with complicated mild traumatic brain injury (TBI) determined
nonoperative after the first head CT. METHODS: A total of 380 patients with mild
TBI and a positive head CT not needing surgery were included. Changes between
first and second head CT were categorized as decreased, increased, or stable.
RESULTS: Three patients required neurosurgical intervention (0.8%) after the
second CT. There were no significant differences in demographics including age,
gender, alcohol consumption, anticoagulation status, time between first and
second CT, Glasgow Coma Scale score at admission and discharge, and incidence of
subarachnoid hemorrhage, epidural hematoma, contusion, or skull fractures between
the operated and nonoperated groups. All patients in the operated group had
subdural hematoma compared with 40.8% in the nonoperated group (P = 0.07). All
operated patients showed symptoms of neurologic worsening after initial head CT,
compared with 2.7% in the nonoperated group (P < 0.001). Moreover, patients who
showed neurologic worsening were more likely to show increased intracranial
bleeding on repeat head CT, whereas patients who did not show neurologic
worsening were more likely to show decreased or stable intracranial bleeding (P =
0.04). CONCLUSIONS: Routine repeat head CT in patients with complicated mild TBI
is very low yield to predict need for delayed surgical intervention. Instead,
serial neurologic examination and observation over the first 8 hours after the
injury is recommended. A second CT scan should be obtained only in patients who
have neurologic worsening.
PMID- 28502690
TI - The Clinical Effect of Postoperative Hyperbaric Oxygen Therapy on Idiopathic
Normal Pressure Hydrocephalus: A Retrospective and Comparative Analysis of 61
Patients with Ventriculoperitoneal Shunt.
AB - OBJECTIVE: The aim of the study was to examine the clinical effect of
postoperative hyperbaric oxygen (HBO) therapy on symptoms and signs in the
ventriculoperitoneal (VP) shunt insertion treatment of idiopathic normal pressure
hydrocephalus (iNPH). METHODS: We conducted a retrospective analysis of 61
patients treated at our institution for iNPH since 2007. Patients were stratified
into 2 groups according to undergoing pure VP shunt with gravitational valves
(group 1) or combined with postoperative HBO therapy (group 2). Clinical
improvements as well as complications were compared between the 2 groups.
RESULTS: There was no significant difference between the 2 groups regarding age,
sexual proportion, body mass index, education years, and the average Normal
Pressure Hydrocephalus Scale score before the surgery, as well as the
complication rate after the surgery (P > 0.05). On average, the total Normal
Pressure Hydrocephalus Scale scores were both increased in the 2 groups at 1, 3,
and 6 months after shunting, with no significant differences (P > 0.05). However,
group 2 tended to increase more compared with group 1, especially 6 months later
after shunting. The increase of cognitive functions was more significant in group
2 (P < 0.05). CONCLUSIONS: HBO therapy combined with VP shunt is expected to
improve the effect of iNPH treatment, especially for cognitive performance.
PMID- 28502691
TI - Long-Term Seizure, Quality of Life, Depression, and Verbal Memory Outcomes in a
Controlled Mesial Temporal Lobe Epilepsy Surgical Series Using Portuguese
Validated Instruments.
AB - OBJECTIVE: We aimed to evaluate long-term surgical outcomes in patients treated
for mesial temporal lobe epilepsy compared with a similar group of patients who
underwent a preoperative evaluation. METHODS: Patient interviews were conducted
by an independent neuropsychologist and included a sociodemographic questionnaire
and validated versions of the Beck Depression Inventory-II, Adverse Events
Profile, Quality of Life in Epilepsy-31, and Rey Auditory Verbal Learning Test.
RESULTS: Seventy-one patients who underwent surgery and 20 who underwent mesial
temporal lobe epilepsy preoperative evaluations were interviewed. After an 81
month mean postoperative follow-up, 44% of the surgical patients achieved
complete seizure relief according to the Engel classification and 68% according
to the International League Against Epilepsy classification. The surgical group
had a significantly lower prevalence of depression (P = 0.002) and drug-related
adverse effects (P = 0.002). Improvement on unemployment (P = 0.02) was achieved
but not on driving or education. Delayed verbal memory recall was impaired in 76%
of the surgical and 65% of the control cases (P = 0.32). Regarding the Quality of
Life in Epilepsy-31, the operated patients scored higher in their total score
(mean, 75.44 vs. mean, 60.08; P < 0.001) and in all but the cognitive functioning
domain irrespective of the follow-up length. Seizure control, Beck Depression
Score, and Adverse Events Profile severity explained 73% of the variance in the
surgical group quality of life. CONCLUSIONS: Our study found that, although
surgical treatment was effective, its impact on social indicators was modest.
Moreover, the self-reported quality of life relied not only on seizure control
but also on depressive symptoms and antiepileptic drug burden.
PMID- 28502693
TI - Prolonged Blood-Brain Barrier Disruption Following Laser Interstitial Ablation in
Epilepsy: A Case Series with a Case Report of Postablation Optic Neuritis.
AB - OBJECTIVE: Laser interstitial thermal therapy has become increasingly popular for
targeting epileptic foci in a minimally invasive fashion. Despite its use in
>1000 patients, the long-term effects of photothermal injury on brain physiology
remain poorly understood. METHODS: We prospectively followed clinical and
radiographic courses of 13 patients undergoing laser ablation for focal epilepsy
by the senior author (N.T.). Only patients with nonenhancing lesions and patients
who had a delayed postoperative magnetic resonance imaging (MRI) scan with
gadolinium administration approximately 6 months after ablation were considered.
Volumetric estimates of the amount of enhancement immediately after ablation and
on the delayed MRI scan were made. RESULTS: Median interval between surgery and
delayed postoperative MRI scan was 6 months (range, 5-8 months). In 12 of 13
cases, persistent enhancement was seen, consistent with prolonged blood-brain
barrier dysfunction. Enhancement, when present, was 9%-67% (mean 30%). There was
no correlation between the time from surgery and the relative percentage of
postoperative enhancement on MRI. The blood-brain barrier remained compromised to
gadolinium contrast for up to 8 months after thermal therapy. There were no
adverse events from surgical intervention; however, 1 patient developed delayed
optic neuritis. CONCLUSIONS: Prolonged incompetence of the blood-brain barrier
produced by thermal ablation may provide a path for delivery of macromolecules
into perilesional tissue, which could be exploited for therapeutic benefit, but
rarely it may result in autoimmune central nervous system inflammatory
conditions.
PMID- 28502694
TI - Phase II trial of the PI3 kinase inhibitor buparlisib (BKM-120) with or without
enzalutamide in men with metastatic castration resistant prostate cancer.
AB - BACKGROUND: Phosphatidylinositol-3-kinase (PI3K) and androgen receptor pathway
activation is common in metastatic castration resistant prostate cancer (mCRPC).
Buparlisib is an oral, pan-class I PI3 kinase inhibitor. METHODS: This was a
multisite single arm phase II trial of buparlisib 100 mg +/- enzalutamide daily
in men with mCRPC whose disease progressed on or who were not candidates for
docetaxel. The primary end-point was the rate of radiographic/clinical
progression-free survival (PFS) at 6 months. RESULTS: Thirty men were accrued:
67% post-docetaxel; median prostate specific antigen (PSA) was 70 ng/dl, 83% had
>=4 prior therapies for mCRPC; 43% received concurrent enzalutamide. The final 6
month PFS rate was estimated to be 10% (95% confidence interval 2.5-23.6%).
Median PFS was 1.9 months and was 3.5 months with concurrent enzalutamide. Median
overall survival was 10.6 months. Concurrent enzalutamide led to a five-fold
reduction in buparlisib concentrations. PSA declines were observed in 23%; no
patients achieved a >=50% decline, and no radiographic responses were observed.
Severe adverse events occurred in four men including respiratory infection and
multi-organ failure, urinary tract obstruction, confusion and one seizure in the
setting of a new central nervous system (CNS) metastasis. Grade III adverse
events were seen in 43% of patients; common toxicities included grade I-II weight
loss, diarrhoea, nausea, fatigue, anorexia, rash, hyperglycemia and anxiety/mood
disorders. CONCLUSIONS: Buparlisib did not demonstrate significant activity in
men with mCRPC, suggesting that PI3K inhibition is not sufficient to reverse
resistant mCRPC progression. Future studies of PI3K pathway inhibitors with
concurrent enzalutamide should develop optimal dosing and focus on selected
patients more likely to benefit.
PMID- 28502695
TI - Selective Activation of Estrogen Receptor alpha Activation Function-1 Is
Sufficient to Prevent Obesity, Steatosis, and Insulin Resistance in Mouse.
AB - Estrogen receptor alpha (ERalpha) regulates gene transcription through two
activation functions (ERalpha-AF1 and ERalpha-AF2). We recently found that the
protection conferred by 17beta-estradiol against obesity and insulin resistance
requires ERalpha-AF2 but not ERalpha-AF1. However, the interplay between the two
ERalpha-AFs is poorly understood in vivo and the metabolic influence of a
specific ERalpha-AF1 action remains to be explored. To this end, wild-type,
ERalpha-deficient, or ERalpha-AF1-deficient ovariectomized female mice were fed a
high-fat diet and concomitantly administered with vehicle or tamoxifen, a
selective ER modulator that acts as a ERalpha-AF1 agonist/ERalpha-AF2 antagonist.
In ovariectomized wild-type mice, tamoxifen significantly reduced food intake and
totally prevented adiposity, insulin resistance, and steatosis. These effects
were abolished in ERalpha-deficient and ERalpha-AF1-deficient mice, revealing the
specific role of ERalpha-AF1 activation. Finally, hepatic gene expression changes
elicited by tamoxifen in wild-type mice were abrogated in ERalpha-AF1-deficient
mice. The combination of pharmacologic and transgenic approaches thus indicates
that selective ERalpha-AF1 activation by tamoxifen is sufficient to elicit
metabolic protection, contrasting with the specific requirement of ERalpha-AF2 in
the metabolic actions of 17beta-estradiol. This redundancy in the ability of the
two ERalpha-AFs to separately mediate metabolic prevention strikingly contrasts
with the contribution of both ERalpha-AFs in breast cancer proliferation,
shedding new light on the therapeutic potential of selective ER modulation.
PMID- 28502697
TI - Impact of high-flux haemodialysis on the probability of target attainment for
oral amoxicillin/clavulanic acid combination therapy.
AB - Clearance of small molecules such as amoxicillin and clavulanic acid is expected
to increase during high-flux haemodialysis, which may result in lower
concentrations and thus reduced efficacy. To date, clearance of
amoxicillin/clavulanic acid (AMC) during high-flux haemodialysis remains largely
unexplored. Using published pharmacokinetic parameters, a two-compartment model
with first-order input was simulated to investigate the impact of high-flux
haemodialysis on the probability of target attainment (PTA) of orally
administered AMC combination therapy. The following
pharmacokinetic/pharmacodynamic targets were used to calculate the PTA. For
amoxicillin, the time that the free concentration remains above the minimum
inhibitory concentration (MIC) of >=50% of the dosing period (>=50%fT>MIC) was
used. For clavulanic acid, the time that the free concentration was >0.1 mg/L of
>=45% of the dosing period (>=45%fT>0.1 mg/L) was used. Dialysis clearance
reported in low-flux haemodialysis for both compounds was doubled to represent
the likely clearance during high-flux haemodialysis. Monte Carlo simulations were
performed to produce concentration-time profiles over 10 days in 1000 virtual
patients. Seven different regimens commonly seen in clinical practice were
explored. When AMC was dosed twice daily, the PTA was mostly >=90% for both
compounds regardless of when haemodialysis commenced. When administered once
daily, the PTA was 20-30% for clavulanic acid and >=90% for amoxicillin. The
simulations suggest that once-daily orally administered AMC in patients receiving
high-flux haemodialysis may result in insufficient concentrations of clavulanic
acid to effectively treat infections, especially on days when haemodialysis
occurs.
PMID- 28502696
TI - Reverse zoonotic transmission of community-associated MRSA ST1-IV to a dairy cow.
PMID- 28502698
TI - Effectiveness of a fine motor skills rehabilitation program on upper limb
disability, manual dexterity, pinch strength, range of fingers motion,
performance in activities of daily living, functional independency, and general
self-efficacy in hand osteoarthritis: A randomized clinical trial.
AB - STUDY DESIGN: A randomized clinical trial. INTRODUCTION: Rehabilitation
treatments for improving fine motor skills (FMS) in hand osteoarthritis (HOA)
have not been well explored yet. PURPOSE OF THE STUDY: To assess the
effectiveness of a rehabilitation program on upper limb disability, independence
of activities of daily living (ADLs), fine motor abilities, functional
independency, and general self-efficacy in older adults with HOA. METHODS: About
45 adults (74-86 years) with HOA were assigned to an experimental group for
completing an FMS intervention or a control group receiving conventional
occupational therapy. Both interventions were performed 3 times/wk, 45 minutes
each session, during 8 weeks. Upper limb disability, performance in ADLs, pinch
strength, manual dexterity, range of fingers motion, functional independency, and
general self-efficacy were assessed at baseline, immediately after treatment, and
after 2 months of follow-up. RESULTS: FMS group showed significant improvements
with a small effect size on manual dexterity (P <= .034; d >= 0.48) and a
moderate-high effect on range of index (P <= .018; d >= 0.58) and thumb (P <=
.027; d >= 0.39) motion. The control group showed a significant worse range of
motion over time in some joints at the index (P <= .037; d >= 0.36) finger and
thumb (P <= .017; d >= 0.55). CONCLUSIONS: A rehabilitation intervention for FMS
may improve manual dexterity and range of fingers motion in HOA, but its effects
on upper limb disability, performance in ADLs, pinch strength, functionality, and
self-efficacy remain uncertain. Specific interventions of the hand are needed to
prevent a worsening in range of finger motion. LEVEL OF EVIDENCE: 1b.
PMID- 28502692
TI - What Factors Determine Treatment Outcome in Aneurysmal Subarachnoid Hemorrhage in
the Modern Era? A Post Hoc STASH Analysis.
AB - BACKGROUND: The management of aneurysmal subarachnoid hemorrhage (aSAH) has
changed dramatically in the last few decades with the publication of a few major
studies, including ISAT (International Subarachnoid Aneurysm Trial, the
International Cooperative Study on the Timing of Aneurysm Surgery Study). The aim
of this study is to analyze the outcome of patients with aSAH based on a
contemporary series, identify the risk factors for poor outcome, and focus on
patients with good-grade aSAH (to match the ISAT cohort). METHODS: Baseline
demographic and outcome data (modified Rankin Scale) were available for the 803
patients recruited from the STASH (Simvastatin in Aneurysmal Subarachnoid
Haemorrhage) trial for post hoc analysis, using a chi2 test or 2-sample t test.
Logistic regression analysis was performed to assess the risk factors for poor
outcome at 6 months. Propensity matched analysis comparing coiling and clipping,
and subgroup analysis of good-grade patients (World Federation of Neurosurgical
Societies grade I-II) were also performed. RESULTS: Logistic regression analysis
showed that the treatment modality (i.e., coiling or clipping) was not associated
with poor outcome at 6 months (P = 0.839). The risk factors associated with poor
outcome at 6 months were poor admission World Federation of Neurosurgical
Societies grade (P < 0.0001), Fisher grade on initial computed tomography scan (P
= 0.013), and the development of delayed cerebral ischemia (P < 0.0001). Subgroup
analysis for good-grade patients only showed that 82% of patients after coiling
and 78% of patients after clipping were classed as good outcome at 6 months (P =
0.181). CONCLUSIONS: In the current era of aSAH management, apart from patients'
admission status, SAH blood load and the development of delayed cerebral
ischemia, treatment modality with either coiling or clipping was not associated
with poor outcome difference at 6 months.
PMID- 28502701
TI - FastPCR: An in silico tool for fast primer and probe design and advanced sequence
analysis.
AB - Polymerase chain reaction (PCR) is one of the most important laboratory
techniques used in molecular biology, genetics and molecular diagnostics. The
success of a PCR-based method largely depends on the correct nucleic acid
sequence analysis in silico prior to a wet-bench experiment. Here, we report the
development of an online Java-based software for virtual PCR on linear or
circular DNA templates and multiple primer or probe search from large or small
databases. Primer or probe sensitivity and specificity are predicted by searching
a database to find sequences with an optimal number of mismatches, similarity and
stability. The software determines primer location, orientation, efficiency of
binding and calculates primer melting temperatures for standard and degenerate
oligonucleotides. The software is suitable for batch file processing, which is
essential for automation when working with large amounts of data. The online Java
software is available for download at http://primerdigital.com/tools/pcr.html.
Accession numbers for the sequences resulting from this study: EU140956 EU177767
EU867815 EU882730 FJ975775-FJ975780 HM481419 HM481420 KC686837-KC686839 KM262797.
PMID- 28502699
TI - Supraspinatus tendon micromorphology in individuals with subacromial pain
syndrome.
AB - STUDY DESIGN: Cross-sectional cohort. INTRODUCTION: Tendon collagen organization
can be estimated by peak spatial frequency radius (PSFR) on ultrasound images.
Characterizing PSFR can define the contribution of collagen disruption to
shoulder symptoms. PURPOSE OF THE STUDY: The purpose of this was to characterize
the (1) supraspinatus tendon PSFR in participants with subacromial pain syndrome
(SPS) and healthy controls; (2) PSFR between participants grouped on a tendon
visual quality score; and (3) relationship between PSFR with patient-reported
pain, function, and shoulder strength. METHODS: Participants with SPS (n = 20)
and age, sex, and arm-dominance-matched healthy controls (n = 20) completed
strength testing in scaption and external rotation, and patient-reported pain,
and functional outcomes. Supraspinatus tendon ultrasound images were acquired,
and PSFR was calculated for a region of interest 15 mm medial to the
supraspinatus footprint. PSFR was compared between groups using an independent t
test and an analysis of variance to compare between 3 groups for visually
qualitatively rated tendon abnormalities. Relationships between PSFR with pain,
function, and strength were assessed using Pearson correlation coefficient.
RESULTS: Supraspinatus tendon PSFR was not different between groups (P = .190) or
tendon qualitative ratings (P = .556). No relationship was found between PSFR and
pain, functional loss, and strength (P > .05). CONCLUSIONS: Collagen disruption
(PSFR) measured via ultrasound images of the supraspinatus tendon was not
different between participants with SPS or in those with visually rated tendon
defects. PSFR is not related to shoulder pain, function, and strength, suggesting
that supraspinatus tendon collagen disorganization may not be a contributing
factor to shoulder SPS. However, collagen disruption may not be isolated to a
single region of interest. LEVEL OF EVIDENCE: 3b: case-control study.
PMID- 28502700
TI - Fetal Alcohol Spectrum Disorders (FASD) and competency to stand trial (CST):
Suggestions for a 'best practices' approach to forensic evaluation.
AB - Fetal Alcohol Spectrum Disorders (FASD), an umbrella term for neurodevelopmental
conditions caused by prenatal alcohol exposure, is overrepresented in the U.S.
juvenile and adult criminal justice systems. The brain damage in FASD manifests
in a combination of cognitive and adaptive impairments that potentially reduce
ability to function adequately during the criminal justice process, including
capacity to stand trial (CST). Despite the high risk of arrest and conviction in
this population, relatively little research guides CST assessment for defendants
who have or may have FASD. Therefore, the purpose of this article is to describe
how FASD may affect CST and suggest ways forensic professionals might modify
assessment protocols to address possible effects of FASD-associated impairments
on adjudicative capacity.
PMID- 28502702
TI - Deep sequencing reveals complex mechanisms of microRNA regulation during retinoic
acid-induced neuronal differentiation of mesenchymal stem cells.
AB - Retinoic acid (RA) has an important role in nervous system development; exogenous
RA could induce stem cells towards neural lineage cells. However, the miRNA
regulation mechanism and biological process of this induction require further
exploration. In this study, using high-throughput sequencing results, we
evaluated the microRNA profiles of neurally differentiated adipose-derived
mesenchymal stem cells (ASCs), summarized several crucial microRNAs that
profoundly contributed to the differentiation process, and speculated that
several miRNAs were likely to mimic RA or other factors to induce the neuronal
differentiation of stem cells. The GO terms and KEGG PATHWAY in the DAVID tool
were used to elucidate the biological process of RA induction. Finally, we
described a network for clarifying the relationship among the miRNAs, target
genes and signaling pathways. These findings will be beneficial for understanding
the induction mechanism and supporting the application of RA in stem cell
transformation.
PMID- 28502703
TI - Cell death induced by mitochondrial complex I inhibition is mediated by Iron
Regulatory Protein 1.
AB - Mitochondrial dysfunction and oxidative damage, often accompanied by elevated
intracellular iron levels, are pathophysiological features in a number of
neurodegenerative processes. The question arises as to whether iron
dyshomeostasis is a consequence of mitochondrial dysfunction. Here we have
evaluated the role of Iron Regulatory Protein 1 (IRP1) in the death of SH-SY5Y
dopaminergic neuroblastoma cells subjected to mitochondria complex I inhibition.
We found that complex I inhibition was associated with increased levels of
transferrin receptor 1 (TfR1) and iron uptake transporter divalent metal
transporter 1 (DMT1), and decreased levels of iron efflux transporter Ferroportin
1 (FPN1), together with increased 55Fe uptake activity and an increased
cytoplasmic labile iron pool. Complex I inhibition also resulted in increased
oxidative modifications and increased cysteine oxidation that were inhibited by
the iron chelators desferoxamine, M30 and Q1. Silencing of IRP1 abolished the
rotenone-induced increase in 55Fe uptake activity and it protected cells from
death induced by complex I inhibition. IRP1 knockdown cells presented higher
ferritin levels, a lower iron labile pool, increased resistance to cysteine
oxidation and decreased oxidative modifications. These results support the
concept that IRP1 is an oxidative stress biosensor that mediates iron
accumulation and cell death when deregulated by mitochondrial dysfunction. IRP1
activation, secondary to mitochondrial dysfunction, may underlie the events
leading to iron dyshomeostasis and neuronal death observed in neurodegenerative
disorders with an iron accumulation component.
PMID- 28502704
TI - Ketogenic diet leads to O-GlcNAc modification in the BTBRT+tf/j mouse model of
autism.
AB - BACKGROUND: Protein O-linked-beta-N-acetyl glucosamine (O-GlcNAc) is a post
translational modification to Ser/Thr residues that integrates energy supply with
demand. Abnormal O-GlcNAc patterning is evident in several neurological disease
states including epilepsy, Alzheimer's disease and autism spectrum disorder
(ASD). A potential treatment option for these disorders includes the high-fat,
low-carbohydrate, ketogenic diet (KD). The goal of this study was to determine
whether the KD induces changes in O-GlcNAc in the BTBRT+tf/j (BTBR) mouse model
of ASD. METHODS: Juvenile male (5weeks), age-matched C57 or BTBR mice consumed a
chow diet (13% kcal fat) or KD (75% kcal fat) for 10-14days. Following these
diets, brain (prefrontal cortex) and liver were examined for gene expression
levels of key O-GlcNAc mediators, global and protein specific O-GlcNAc as well as
indicators of energy status. RESULTS: The KD reduced global O-GlcNAc in the
livers of all animals (p<0.05). Reductions were likely mediated by lower protein
levels of O-GlcNAc transferase (OGT) and increased O-GlcNAcase (OGA) (p<0.05). In
contrast, no differences in global O-GlcNAc were noted in the brain (p>0.05), yet
OGT and OGA expression (mRNA) were elevated in both C57 and BTBR animals
(p<0.05). CONCLUSIONS: The KD has tissue specific impacts on O-GlcNAc. Although
levels of O-GlcNAc play an important role in neurodevelopment, levels of this
modification in the juvenile mouse brain were stable with the KD despite large
fluctuations in energy status. This suggests that it is unlikely that the KD
exerts it therapeutic benefit in the BTBR model of ASD by O-GlcNAc related
pathways.
PMID- 28502706
TI - Reprogramming of central carbon metabolism in cancer stem cells.
AB - Cancer metabolism has been studied for years and adopted in the clinic for
monitoring disease progression and therapy response. Despite our growing
knowledge of a distinctly altered metabolic behavior in cancer, drugs targeting
cancer metabolism have remained less than promising. Recent efforts in cancer
stem cell (CSC) biology suggest that a subpopulation of tumor-initiating cells
within the tumor bulk represents the root of tumor recurrence and therapy
resistance. In recent years, metabolic phenotype of CSCs of various tumor types
has been identified. This breakthrough has shed light on the underlying mechanism
by which CSCs maintain stemness, confer resistance to therapies and initiate
tumor relapse. The distinct metabolic characteristics of CSCs compared to non
CSCs provide an opportunity to target CSCs more specifically and have become a
major focus in cancer research in recent years with substantial efforts conducted
towards discovering clinical targets. This perspective article summarizes the
current knowledge of CSC metabolism in carcinogenesis and highlights the
potential of targeting CSC metabolism for therapy.
PMID- 28502705
TI - BAG-1M co-activates BACE1 transcription through NF-kappaB and accelerates Abeta
production and memory deficit in Alzheimer's disease mouse model.
AB - Accumulation of amyloid beta protein (Abeta)-containing neuritic plaques in the
brain is a neuropathological feature of Alzheimer's disease (AD). The beta-site
APP-cleaving enzyme 1 (BACE1) is essential for Abeta generation and dysregulation
of BACE1 expression may lead to AD pathogenesis. Bcl-2-associated athanogen 1M
(BAG-1M), initially identified as an anti-apoptotic protein, has also been found
to be highly expressed in the same neurons that contain intracellular amyloid in
the hippocampus of AD patient. In this report, we found that over-expression of
BAG-1M enhances BACE1-mediated cleavage of amyloid precursor protein (APP) and
Abeta production by up-regulating BACE1 gene transcription. The regulation of
BACE1 transcription by BAG-1M was dependent on NF-kappaB, as BAG-1M complexes NF
kappaB at the promoter of BACE1 gene and co-activates NF-kappaB-facilitated BACE1
transcription. Moreover, expression of BAG-1M by lentiviral vector in the
hippocampus of AD transgenic model mice promotes Abeta generation and formation
of neuritic plaque, and subsequently accelerates memory deficits of the mice.
These results provide evidence for an emerging role of BAG-1M in the regulation
of BACE1 expression and AD pathogenesis and that targeting the BAG-1M-NF-kappaB
complex may provide a mechanism for inhibiting Abeta production and plaque
formation.
PMID- 28502707
TI - Surgical Innovation in Sarcoma Surgery.
AB - The field of orthopaedic oncology relies on innovative techniques to resect and
reconstruct a bone or soft tissue tumour. This article reviews some of the most
recent and important innovations in the field, including biological and implant
reconstructions, together with computer-assisted surgery. It also looks at
innovations in other fields of oncology to assess the impact and change that has
been required by surgeons; topics including surgical margins, preoperative
radiotherapy and future advances are discussed.
PMID- 28502708
TI - 2017 HRS expert consensus statement on magnetic resonance imaging and radiation
exposure in patients with cardiovascular implantable electronic devices.
PMID- 28502709
TI - Organizational Innovation of Apical Actin Filaments Drives Rapid Pollen Tube
Growth and Turning.
AB - Polarized tip growth is a fundamental cellular process in many eukaryotes. In
this study, we examined the dynamic restructuring of the actin cytoskeleton and
its relationship to vesicle transport during pollen tip growth in Arabidopsis. We
found that actin filaments originating from the apical membrane form a
specialized structure consisting of longitudinally aligned actin bundles at the
cortex and inner cytoplasmic filaments with a distinct distribution. Using actin
based pharmacological treatments and genetic mutants in combination with FRAP
(fluorescence recovery after photobleaching) technology to visualize the
transport of vesicles within the growth domain of pollen tubes, we demonstrated
that cortical actin filaments facilitate tip-ward vesicle transport. We also
discovered that the inner apical actin filaments prevent backward movement of
vesicles, thus ensuring that sufficient vesicles accumulate at the pollen tube
tip to support the rapid growth of the pollen tube. The combinatorial effect of
cortical and internal apical actin filaments perfectly explains the generation of
the inverted "V" cone-shaped vesicle distribution pattern at the pollen tube tip.
When pollen tubes turn, apical actin filaments at the facing side undergo
depolymerization and repolymerization to reorient the apical actin structure
toward the new growth direction. This actin restructuring precedes vesicle
accumulation and changes in tube morphology. Thus, our study provides new
insights into the functional relationship between actin dynamics and vesicle
transport during rapid and directional pollen tube growth.
PMID- 28502710
TI - Graduating Pediatric Residents Entering the Hospital Medicine Workforce, 2006
2015.
AB - OBJECTIVE: In October 2016, the American Board of Medical Specialties approved
the petition for pediatric hospital medicine (PHM) to become the newest pediatric
subspecialty. Knowledge about residents entering the PHM workforce is needed to
inform certification and fellowship accreditation. This study describes the
characteristics of graduating pediatric residents with PHM positions and
identifies factors associated with postresidency position choices. METHODS: We
analyzed data from the American Academy of Pediatrics Annual Survey of Graduating
Residents, 2006-2015. Chi-square tests were used to compare responses between
residents entering PHM to those entering subspecialty fellowships, and to compare
residents entering PHM at community and tertiary-care hospitals. We used
multivariable logistic regression to identify associations between resident and
training characteristics and position choices. RESULTS: A total of 5969
respondents completed the survey (60.6% response rate); 593 (10.3%) reported that
they were entering PHM and 1954 (33.9%) reported subspecialty fellowships. Of
residents entering PHM, 345 (60.7%) reported positions at tertiary-care hospitals
and 194 (34.2%) reported positions at community hospitals. Seventy percent of
residents entering PHM envisioned long-term PHM careers, with PHM career goals
more frequently reported among residents entering community hospitalist positions
(P < .01). In multivariable analysis, residents entering PHM were significantly
more likely to be female, to have children, to report that family factors limited
their job selection, and to have higher levels of educational debt than residents
entering fellowships. CONCLUSIONS: Factors associated with postresidency PHM
positions, including substantial educational debt and sociodemographic
characteristics, may influence the development of the field as the specialty
pursues fellowship accreditation.
PMID- 28502711
TI - An improved method to measure lipase activity in aqueous media.
AB - An improved method based on the p-nitrophenyl long chain esters method is
proposed for measuring lipase hydrolytic activity in aqueous media. Using
ethylene glycol as co-solvent for hydrophobic p-nitrophenyl substrates in aqueous
buffer, lipase activity is measured by following the release of p-nitrophenol.
This fast and easy to handle method improves the solubility of both substrate and
product, and also the stability of the substrate. It avoids the use of solvents
such as ethanol or propanol, permits the comparison of all the p-nitrophenol acyl
ester substrates and allows the influence of ions like Ca+2 to be studied, while
avoiding turbidity in the reaction medium.
PMID- 28502712
TI - Ligation-mediated PCR with a back-to-back adapter reduces amplification bias
resulting from variations in GC content.
AB - Ligation-mediated polymerase chain reaction (LM-PCR) is a common technique for
amplification of a pool of DNA fragments. Here, a double-stranded oligonucleotide
consisting of two primer sequences in back-to-back orientation was designed as an
adapter for LM-PCR. When DNA fragments were ligated with this adapter, the
fragments were sandwiched between two adapters in random orientations. In the
ensuing PCR, ligation products linked at each end to an opposite side of the
adapter, i.e. to a distinct primer sequence, were preferentially amplified
compared with products linked at each end to an identical primer sequence. The
use of this adapter in LM-PCR reduced the impairment of PCR by substrate DNA with
a high GC content, compared with the use of traditional LM-PCR adapters. This
result suggested that our method has the potential to contribute to reduction of
the amplification bias that is caused by an intrinsic property of the sequence
context in substrate DNA. A DNA preparation obtained from a chromatin
immunoprecipitation assay using pulldown of a specific form of histone H3 was
successfully amplified using the modified LM-PCR, and the amplified products
could be used as probes in a fluorescence in situ hybridization analysis.
PMID- 28502713
TI - An autopsy case of fatal acute peritonitis complicated by illegal acupuncture
therapy.
AB - Acupuncture is an alternative medical therapy and widely practiced in Northeast
Asia. Although it is known as a safe procedure, complications including
infection, pneumothorax, hemorrhage, and cardiac tamponade have been reported.
The authors present a rare case of fatal acute peritonitis due to penetration of
acupuncture needles directly into the abdominal and pelvic cavity. The victim was
a 55-year-old woman who had a recent history of chemo-radiotherapy due to breast
cancer. She was collapsed three days after receiving acupuncture. She had
symptoms of fever and chilling sensation, general myalgia, and vomiting during
three days. The autopsy revealed several needle marks in the lower abdomen and
180ml of bloody exudate in the abdominal cavity. There was no visible intestinal
perforation, but hemorrhagic foci in the mesentery and paracolic area of sigmoid
colon were noted. The deepest portion was 13.5cm from the needle marks on the
abdominal skin. The practitioner had not a Chinese medical license. He was
accused of illegal medical practice and manslaughter. Acute peritonitis
associated with acupuncture might be caused by inadequate sterilization of skin
and needle itself and/or direct mesentery injury.
PMID- 28502714
TI - Why is it so difficult to determine the yield of indoor cannabis plantations? A
case study from the Netherlands.
AB - Together, the Netherlands and Belgium are the largest indoor cannabis producing
countries in Europe. In both countries, legal prosecution procedure of convicted
illicit cannabis growers usually includes recovery of the profits gained.
However, it is not easy to make a reliable estimation of the latter profits, due
to the wide range of factors that determine indoor cannabis yields and eventual
selling prices. In the Netherlands, since 2005, a reference model is used that
assumes a constant yield (g) per plant for a given indoor cannabis plant density.
Later, in 2011, a new model was developed in Belgium for yield estimation of
Belgian indoor cannabis plantations that assumes a constant yield per m2 of
growth surface, provided that a number of growth conditions are met. Indoor
cannabis plantations in the Netherlands and Belgium share similar technical
characteristics. As a result, for indoor cannabis plantations in both countries,
both aforementioned yield estimation models should yield similar yield
estimations. By means of a real-case study from the Netherlands, we show that the
reliability of both models is hampered by a number of flaws and unmet
preconditions. The Dutch model is based on a regression equation that makes use
of ill-defined plant development stages, assumes a linear plant growth, does not
discriminate between different plantation size categories and does not include
other important yield determining factors (such as fertilization). The Belgian
model addresses some of the latter shortcomings, but its applicability is
constrained by a number of pre-conditions including plantation size between 50
and 1000 plants; cultivation in individual pots with peat soil; 600W (electrical
power) assimilation lamps; constant temperature between 20 degrees C and 30
degrees C; adequate fertilizer application and plants unaffected by pests and
diseases. Judiciary in both the Netherlands and Belgium require robust indoor
cannabis yield models for adequate legal prosecution of illicit indoor cannabis
growth operations. To that aim, the current models should be optimized whereas
the validity of their application should be examined case by case.
PMID- 28502715
TI - Identification of mature peptides from pban and capa genes of the moths Heliothis
peltigera and Spodoptera littoralis.
AB - By transcriptome analysis, we identified PBAN and CAPA precursors in the moths
Spodoptera littoralis and Heliothis peltigera which are among the most damaging
pests of agriculture in tropical and subtropical Africa as well as in
Mediterranean countries. A combination of mass spectrometry and
immunocytochemistry was used to identify mature peptides processed from these
precursors and to reveal their spatial distribution in the CNS. We found that the
sites of expression of pban genes, the structure of PBAN precursors and the
processed neuropeptides are very similar in noctuid moths. The sequence of the
diapause hormone (DH; tryptopyrokinin following the signal peptide), however,
contains two N-terminal amino acids more than expected from comparison with
already published sequences of related species. Capa genes of S. littoralis and
H. peltigera encode, in addition to periviscerokinins, a tryptopyrokinin showing
sequence similarity with DH, which is the tryptopyrokinin of the pban gene. CAPA
peptides, which were not known from any noctuid moth so far, are produced in
cells of abdominal ganglia. The shape of the release sites of these hormones in
H. peltigera represents an exceptionally derived trait state and does not
resemble the well-structured abdominal perisympathetic organs which are known
from many other insects. Instead, axons of CAPA cells extensively ramify within
the ventral diaphragm. The novel information regarding the sequences of all
mature peptides derived from pban and capa genes of H. peltigera and S.
littoralis now enables a detailed analysis of the bioactivity and species
specificity of the native peptides, especially those from the hitherto unknown
capa genes, and to explore their interactions with PBAN/DH receptors.
PMID- 28502716
TI - Neuropeptides predicted from the transcriptome analysis of the gray garden slug
Deroceras reticulatum.
AB - The gray garden slug, Deroceras reticulatum (Gastropoda: Pulmonata), is one of
the most common terrestrial molluscs. Research for this slug has focused mainly
on its ecology, biology, and management due to the severe damage it causes on a
wide range of vegetables and field crops. However, little is known about
neuropeptides and hormonal signalings. This study, therefore, aimed to establish
the transcriptome of D. reticulatum and to identify a comprehensive repertoire of
neuropeptides in this slug. Illumina high-throughput sequencing of the whole body
transcriptome of D. reticulatum generated a total of 5.9 billion raw paired-end
reads. De novo assembly by Trinity resulted in 143,575 transcripts and further
filtration selected 120,553 unigenes. Gene Ontology (GO) terms were assigned to
30,588 unigenes, composed of biological processes (36.9%), cellular components
(30.2%) and molecular functions (32.9%). Functional annotation by BLASTx revealed
39,987 unigenes with hits, which were further categorized into important
functional groups based on sequence abundance. Neuropeptides, ion channels,
ribosomal proteins, G protein-coupled receptors, detoxification, immunity and
cytoskeleton-related sequences were dominant among the transcripts. BLAST
searches and PCR amplification were used to identify 65 putative neuropeptide
precursor genes from the D. reticulatum transcriptome, which include achatin,
AKH, allatostatin A, B and C, allatotropin, APGWamide, CCAP, cerebrin,
conopressin, cysteine-knot protein hormones (bursicon alpha/beta and GPA2/GPB5),
elevenin, FCAP, FFamide, FVamide (enterin, fulicin, MIP and PRQFVamide), GGNG,
GnRH, insulin, NdWFamide, NKY, PKYMDT, PRXamide (myomodulin, pleurin and sCAP),
RFamide (CCK/SK, FMRFamide, FxRIamide, LFRFamide, luqin and NPF), and tachykinin.
Over 330 putative peptides were encoded by these precursors. Comparative analysis
among different molluscan species clearly revealed that, while D. reticulatum
neuropeptide sequences are conserved in Mollusca, there are also some unique
features distinct from other members of this species. This is the first
transcriptome-wide report of neuropeptides in terrestrial slugs. Our results
provide comprehensive transcriptome data of the gray garden slug, with a more
detailed focus on the rich repertoire of putative neuropeptide sequences, laying
the foundation for molecular studies in this terrestrial slug pest.
PMID- 28502717
TI - Preferential accumulation of gold nanorods into human skin hair follicles: Effect
of nanoparticle surface chemistry.
AB - HYPOTHESIS: Gold nanoparticles (GNP) are considered an ideal model to help
understanding the nano-skin interface. The surface functionality of gold nanorods
(GNR) is expected to influence the uptake of nanoparticles into specific targets
of skin such as hair follicles or dermis. Hence, it should be possible to modify
the surface chemistry of GNP to achieve more targeted and safe skin therapy.
EXPERIMENTS: GNR functionalized with various surface ligands (neutral, anionic,
cationic, and hydrophobic) were evaluated for their accumulation into hair
follicles of human skin sheets using ex-vivo setup. The extent of GNR
accumulation into hair follicles and other skin compartments was quantified by
inductively coupled plasma-optical emission spectroscopy (ICP-OES), and their
spatial distribution through skin layers was investigated by laser ablation
inductively coupled plasma-mass spectroscopy (LA-ICP-MS). RESULTS: The lipophilic
properties of sebum-rich hair follicles enhanced the accumulation of hydrophobic
polystyrene (PS)-GNR into hair follicles (~13% of the total applied dose), while
neutral polyethylene glycol (PEG)-GNR were distributed into all skin
compartments, especially the dermis (~11.5% of the total applied dose), which
exhibits hydrophilic characteristics. Charged GNR showed a negligible percentage
of penetration into any of the skin compartments. GNR could be a promising
approach for targeted skin disease treatment and transdermal administration of
drugs and therapy.
PMID- 28502718
TI - Mitochondrial ND5 mutation mediated elevated ROS regulates apoptotic pathway
epigenetically in a P53 dependent manner for generating pro-cancerous phenotypes.
AB - We have previously observed concomitant events of mutations in mitochondrial and
nuclear genes, along with elevated reactive oxygen species (ROS) and differential
methylation within the promoters of nuclear genes in tumors and in vitro
experiments of tumorigenesis. These observations have made it pertinent to
replicate and understand the role of acquired mitochondrial condition in tuning a
cell to accomplish a pro-cancerous state. Using a codon optimized vector system
for exogenous over-expression and mitochondrial localization; we have
characterized here the role of over-expressed wild type mtND5 and one of its non
synonymous somatic mutation, ND5:P265H. The ectopically over-expressed ND5:P265H
in mitochondria resulted in a reduced Complex I activity, generation of higher
ADP/ATP ratio, reactive oxygen species (ROS) and carbonylation of proteins as
compared to mock-transfected cells. Cells over-expressing mtND5 variant produced
both peroxide as well as super-oxide ROS; the generation of which was dependent
on the functional status of P53; modulating epigenetically the expression of key
apoptosis pathway genes. The pro-cancerous phenotypes, of anchorage dependent and
independent growth; increased glucose uptake and lactate production, were
selectively observed only in P53 non-functional cells over-expressing mutant
ND5:P265H. We propose that somatic mutation in mtND5 resulting in down-regulated
complex I enzyme activity, elevated ROS and up-regulation of a set of nuclear
anti-apoptotic genes epigenetically in the P53 dysfunctional cellular background,
has provided a unique understanding of the molecular mechanism of mitochondrial
mutation; and the concomitant existence of somatically acquired mitochondrial and
nuclear p53 mutations, in cancer progression and promotion.
PMID- 28502719
TI - Re: Effectiveness of Adjuvant Chemotherapy After Radical Nephroureterectomy for
Locally Advanced and/or Positive Regional Lymph Node Upper Tract Urothelial
Carcinoma.
PMID- 28502720
TI - Insights into the chicken IgY with emphasis on the generation and applications of
chicken recombinant monoclonal antibodies.
AB - The advantages of chicken (Gallus gallus domesticus) antibodies as
immunodiagnostic and immunotherapeutic biomolecules has only been recently
recognized. Even so, chicken antibodies remain less-well characterized than their
mammalian counterparts. This review aims at providing a current overview of the
structure, function, development and generation of chicken antibodies.
Additionally, brief but comprehensive insights into current knowledge pertaining
to the immunogenetic framework and diversity-generation of the chicken
immunoglobulin repertoire which have contributed to the establishment of
recombinant chicken mAb-generating methods are discussed. Focus is provided on
the current methods used to generate antibodies from chickens with added emphasis
on the generation of recombinant chicken mAbs and its derivative formats. The
advantages and limitations of established protocols for the generation of chicken
mAbs are highlighted. The various applications of recombinant chicken mAbs and
its derivative formats in immunodiagnostics and immunotherapy are further
detailed.
PMID- 28502722
TI - Radiotherapy Rescue of a Nivolumab-Refractory Immune Response in a Patient with
PD-L1-Negative Metastatic Squamous Cell Carcinoma of the Lung.
PMID- 28502721
TI - MET Exon 14 Skipping Mutations in Lung Adenocarcinoma: Clinicopathologic
Implications and Prognostic Values.
AB - INTRODUCTION: Response to mesenchymal-epithelial transition (MET) inhibitors in
NSCLC with mesenchymal-epithelial transition gene (MET) exon 14 skipping
(METex14) has fueled molecular screening efforts and the search for optimal
therapies. However, further work is needed to refine the clinicopathologic and
prognostic implications of METex14 skipping. METHODS: Among 795 East Asian
patients who underwent a surgical procedure for NSCLC, we screened 45 patients
with quintuple-negative (EGFR-negative/KRAS-negative/anaplastic lymphoma kinase
gene [ALK]-negative/ROS1-negative/ret proto-oncogene [RET]-negative) lung
adenocarcinomas by using reverse-transcriptase polymerase chain reaction and
found 17 patients (37.8%) with METex14 skipping. We also investigated the effect
of small interfering RNA (siRNA) targeting skipping junction in cells with
METex14 skipping. RESULTS: The median age of the 17 patients was 73 years. The
acinar subtype was predominant (52.9%), followed by the solid subtype (35.3%).
MET immunohistochemistry demonstrated 100% sensitivity and 70.4% specificity.
Multivariate analyses showed that patients with METex14 skipping had a higher
recurrence rate than those with ALK fusion (versus METex14 skipping) (hazard
ratio = 0.283, 95% confidence interval: 0.119-0.670) in stage I to IIIA disease;
however, the differences in overall survival were not significant after
adjustment for pathologic stage (p = 0.669). Meanwhile, siRNA decreased MET
driven signaling pathways in Hs746T cells, and combined treatment with siRNA and
crizotinib inhibited cell proliferation in crizotinib-resistant H596 cells.
CONCLUSIONS: The prevalence of METex14 skipping was quite high in East Asian
patients without other driver mutations in lung adenocarcinomas. METex14 skipping
was associated with old age, the acinar or solid histologic subtype, and high MET
immunohistochemical expression. The prognosis of patients with METex14 skipping
was similar to that of patients with major driver mutations. siRNA targeting the
junction of METex14 skipping could inhibit MET-driven signaling pathways in cells
with METex14 skipping.
PMID- 28502723
TI - Histologic Transformation in NSCLC with PD-1 therapy.
PMID- 28502724
TI - Durable Response to Afatinib in Lung Adenocarcinoma Harboring NRG1 Gene Fusions.
PMID- 28502725
TI - Molecular Diagnosis of Mosaic Overgrowth Syndromes Using a Custom-Designed Next
Generation Sequencing Panel.
AB - Recent studies have discovered a group of overgrowth syndromes, such as
congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies
(CLOVES) syndrome, Proteus syndrome, and megalencephaly-capillary malformation
polymicrogyria (MCAP) syndrome, are caused by somatic activating variants in
genes involved in the phosphatidylinositol 3-kinase/AKT/mechanistic target of
rapamycin pathway. Because of the low-abundance nature of these variants, Sanger
sequencing often yields negative results. We have developed and validated a next
generation sequencing (NGS) panel that targets all known variants associated with
these syndromes. Fifty cases, including two prenatal cases, were tested using the
panel. A pathogenic variant in the PIK3CA, PIK3R2, or AKT1 gene was identified in
28 of the 50 cases with the variant allele frequencies ranging from 1.0% to
49.2%. These variants were only present in the affected tissues in most of the
cases, demonstrating a causal role in the development of these diseases. In vitro
cell culture showed significant enrichment of the cells harboring variant
alleles, suggesting that these variants render growth advantages to mutant cells.
Phenotype-genotype correlation analysis showed PIK3CA mutation hotspots at
residues E542, E545, and H1047 are often associated with CLOVES syndrome, whereas
PIK3CA G914R is preferentially related to MCAP. We thus demonstrate that NGS
technology is highly sensitive for detecting low-level mosaicism and can
facilitate clinical diagnosis of mosaic overgrowth syndromes in both prenatal and
postnatal settings.
PMID- 28502726
TI - Utility of NIST Whole-Genome Reference Materials for the Technical Validation of
a Multigene Next-Generation Sequencing Test.
AB - The sensitivity and specificity of next-generation sequencing laboratory
developed tests (LDTs) are typically determined by an analyte-specific approach.
Analyte-specific validations use disease-specific controls to assess an LDT's
ability to detect known pathogenic variants. Alternatively, a methods-based
approach can be used for LDT technical validations. Methods-focused validations
do not use disease-specific controls but use benchmark reference DNA that
contains known variants (benign, variants of unknown significance, and
pathogenic) to assess variant calling accuracy of a next-generation sequencing
workflow. Recently, four whole-genome reference materials (RMs) from the National
Institute of Standards and Technology (NIST) were released to standardize methods
based validations of next-generation sequencing panels across laboratories. We
provide a practical method for using NIST RMs to validate multigene panels. We
analyzed the utility of RMs in validating a novel newborn screening test that
targets 70 genes, called NEO1. Despite the NIST RM variant truth set originating
from multiple sequencing platforms, replicates, and library types, we discovered
a 5.2% false-negative variant detection rate in the RM truth set genes that were
assessed in our validation. We developed a strategy using complementary non-RM
controls to demonstrate 99.6% sensitivity of the NEO1 test in detecting variants.
Our findings have implications for laboratories or proficiency testing
organizations using whole-genome NIST RMs for testing.
PMID- 28502728
TI - Technical Validation of a Next-Generation Sequencing Assay for Detecting
Clinically Relevant Levels of Breast Cancer-Related Single-Nucleotide Variants
and Copy Number Variants Using Simulated Cell-Free DNA.
AB - Next-generation sequencing (NGS) is commonly used in a clinical setting for
diagnostic and prognostic testing of genetic mutations to select optimal targeted
therapies. Herein, we describe the development of a custom NGS assay for
detecting single-nucleotide variants (SNVs) and copy number variations (CNVs) in
a panel of 51 genes related to breast cancer. We designed and implemented a
validation strategy in accordance with principles and guidelines developed by the
Next-Generation Sequencing: Standardization of Clinical Testing work group using
artificial, cell-free DNA (cfDNA) with mutant fragments prepared in a simple,
rapid, and cost-effective manner. For SNV detection, our test had 96.30%
sensitivity at mutant allele frequency >=0.5% with high specificity (99.9997%)
and accuracy (99.9996%). For CNV detection, the approach had 95.83% sensitivity
for copy numbers at 1.25* (25.6% extra copies) with high specificity (99.77%) and
accuracy (99.76%). In addition, our NGS-based assay demonstrated high intrarun
and interrun reproducibility, high consistency compared to digital PCR, and a low
cross-contamination rate. An overall assessment using cfDNA and plasma cfDNA
samples demonstrated our custom NGS assay yields a reliable and robust detection
sensitivity with a mutant allele frequency as low as 0.5% for SNVs and copy
number of 1.25* for CNVs.
PMID- 28502729
TI - Improving Mutation Screening in Patients with Colorectal Cancer Predisposition
Using Next-Generation Sequencing.
AB - Identification of genetic alterations is important for family risk assessment in
colorectal cancers. Next-generation sequencing (NGS) technologies provide useful
tools for single-nucleotide and copy number variation (CNV) identification in
many genes and samples simultaneously. Herein, we present the validation of
current Multiplicom MASTR designs of mismatch repair combined to familial
adenomatous polyposis genes in a single PCR reamplification test for eight DNA
samples simultaneously on a MiSeq apparatus. Blood samples obtained from 224
patients were analyzed. We correctly identified the 97 mutations selected among
48 samples tested in a validation cohort. PMS2 NGS analysis of the eight positive
controls identified single-nucleotide variations not detected with targeted
referent methods. As NGS method could not discriminate if some of them were
assigned to PMS2 or pseudogenes, only CNV analysis with multiplex ligand probe
dependent amplification confirmation was retained for clinical use. Twenty-seven
new variants of unknown significance, 21 disease-causing variants, and two CNVs
were detected among the 176 patient samples analyzed in diagnosis routine. MUTYH
disease-causing mutations were identified in two patient samples assessed for
mismatch repair testing, confirming that this method facilitates accurate and
rapid individual risk assessments. In one sample, the MUTYH mutation was
associated with a MSH6 disease-causing mutation, suggesting that this method is
helpful to identify additional cancer risk modifiers and provides a useful tool
to optimize clinical issues.
PMID- 28502727
TI - Concordance between Research Sequencing and Clinical Pharmacogenetic Genotyping
in the eMERGE-PGx Study.
AB - There has been extensive debate about both the necessity of orthogonal
confirmation of next-generation sequencing (NGS) results in Clinical Laboratory
Improvement Amendments-approved laboratories and return of research NGS results
to participants enrolled in research studies. In eMERGE-PGx, subjects underwent
research NGS using PGRNseq and orthogonal targeted genotyping in clinical
laboratories, which prompted a comparison of genotyping results between
platforms. Concordance (percentage agreement) was reported for 4077 samples
tested across nine combinations of research and clinical laboratories. Retesting
was possible on a subset of 1792 samples, and local laboratory directors
determined sources of genotype discrepancy. Research NGS and orthogonal clinical
genotyping had an overall per sample concordance rate of 0.972 and per variant
concordance rate of 0.997. Genotype discrepancies attributed to research NGS were
because of sample switching (preanalytical errors), whereas the majority of
genotype discrepancies (92.3%) attributed to clinical genotyping were because of
allele dropout as a result of rare variants interfering with primer hybridization
(analytical errors). These results highlight the analytical quality of clinically
significant pharmacogenetic variants derived from NGS and reveal important areas
for research and clinical laboratories to address with quality management
programs.
PMID- 28502730
TI - Overgrowth Syndromes Caused by Somatic Variants in the Phosphatidylinositol 3
Kinase/AKT/Mammalian Target of Rapamycin Pathway.
AB - Somatic variants have been well described in tumorigenesis; however, they are
only recently appreciated in other human disorders, such as mosaic overgrowth
syndromes. Although overgrowth is a manifestation in many genetic syndromes, not
all overgrowth syndromes are inherited. Mosaic somatic variants have been lately
described in several overgrowth disorders, such as Proteus syndrome, CLOVES
(congenital, lipomatous, overgrowth, vascular malformations, epidermal nevi, and
spinal/skeletal anomalies and/or scoliosis) syndrome, and
megalencephalyepolymicrogyria-polydactyly-hydrocephalus syndrome. These syndromes
are caused by somatic variants in the genes associated with the
phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway,
resulting in a spectrum of overgrowth syndromes with overlapping features that
could be difficult to distinguish based on phenotypic presentations alone. In
addition, Sanger sequencing is ineffective for the detection of a causal variant
because of the mosaic nature of these variants, whereas targeted next-generation
sequencing technology offers a deeper sequencing coverage and allows the
detection of low-level mosaicism. Recent studies have shown that the causal
variants are only present in the affected tissues in most cases, and can be
enriched by in vitro tissue culture. In this review, we describe several mosaic
somatic overgrowth syndromes caused by variants in genes of the
phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling
pathway, their phenotypic and molecular spectrum, and the clinical utility of
next-generation sequencing technology in the diagnosis of these disorders.
PMID- 28502731
TI - The influence of a probiotic supplementation on memory in quail suggests a role
of gut microbiota on cognitive abilities in birds.
AB - The gut microbiota is involved in host behaviour and memory in mammals.
Consequently, it may also influence emotional behaviour and memory in birds.
Quail from two genetic lines with different fearfulness (LTI: long tonic
immobility, n=37; STI: short tonic immobility, n=32) were either or not
supplemented with a probiotic (Pediococcus acidilactici) from hatching. Emotional
reactivity was measured in a tonic immobility test (d6 and 7 of age) and two open
field tests (d13-15; d22-24). Memory was measured in a test rewarded with
mealworms, where quail had to remember the cups previously visited (d34-36).
Quail endured a 5-days stress period from days 17 to 21 to help revealing the
potentially beneficial effect of the probiotic. As expected, STI quail were less
fearful compared to the LTI quail (p<0.05). Probiotic supplementation had no
effect on most measures of emotional reactivity (p>0.05), except in the tonic
immobility test where supplemented STI quail had lower immobility duration
(p=0.0001). Regarding the memory test, the two lines had similar performances.
Quail fed with probiotics made fewer errors (p=0.040). There was no significant
correlation between traits of emotional reactivity and of memory. In conclusion,
the supplementation with Pediococcus acidilactici as a probiotic, affected a
specific trait of emotional reactivity in STI quail, and improved memory in both
lines, whichstrengthens the idea that the influence of gut microbiota on the host
behaviour and memory seen in mammals is shared by birds.
PMID- 28502732
TI - Swimming exercise prevents behavioural disturbances induced by an
intracerebroventricular injection of amyloid-beta1-42 peptide through modulation
of cytokine/NF-kappaB pathway and indoleamine-2,3-dioxygenase in mouse brain.
AB - Emerging evidence indicates that the activation of indoleamine-2,3-dioxygenase
(IDO), a first and rate-limiting enzyme in the kynurenine (KYN) pathway, is
involved in amyloid-beta (Abeta1-42)-neurotoxicity and Alzheimer's disease (AD)
pathogenesis. Physical exercise has been considered an effective intervention in
AD, attenuating or limiting their progression. Nevertheless, the neurobiological
mechanisms underlying the neuroprotective effects of exercise have not yet been
fully elucidated. In present study, we investigated the protective effect of an 8
week swimming training (ST) exercise on cognitive and non-cognitive functions and
its role in modulating biomarkers of KYN pathway, before an
intracerebroventricular (i.c.v.) injection of Abeta1-42 (400pmol/animal;
3MUl/site) peptide in mice. Our results demonstrated that ST was effective in
preventing the following behavioural disturbances caused by Abeta1-42 injection:
memory impairment in the object recognition test and depressive/anxiety-like
behaviour in the tail suspension test and elevated plus-maze test, respectively.
ST abrogated the neuroinflammatory response and neurotrophic deficiency in the
prefrontal cortex and hippocampus induced by Abeta1-42. Also, Abeta1-42 increased
IDO activity, KYN and tryptophan (TRP) levels and KYN:TRP ratio in the prefrontal
cortex and hippocampus - alterations that were blocked by ST. It can be concluded
that ST prevented behavioural and neurobiological deficits induced by Abeta1-42,
and suggest that these neuroprotective effects are likely to involve the
inhibition of inflammation/IDO activation and up-regulation of neurotrophic
factors in brain of mice. Thus, it is possible that physical exercise can be used
as a non-pharmacological approach to alleviates both cognitive and non-cognitive
symptoms of AD.
PMID- 28502734
TI - Transcatheter aortic valve implantation in patients at intermediate surgical
risk.
AB - Transcatheter Aortic Valve Implantation (TAVI) has revolutionized the treatment
of elderly patients with symptomatic severe aortic stenosis (AS). Initially
tested in unoperable or high surgical risk patients, the safety and efficacy of
TAVI has progressively improved, with increasing operators' experience and
continuous technical refinements of the devices and of the delivery systems.
Hence, the extension of clinical indications for TAVI to the intermediate-risk
population has been attracting cardiologists in recent years. This idea was
supported by the results of recent studies suggesting that transfemoral TAVI
might be associated with a survival benefit in both high- and intermediate-risk
patients with severe AS. Therefore, the aim of this review is to summarize the
currently available evidence from multiple observational studies, substudies from
large country registries, mached group comparisons, a substudy of randomized
studies, and randomized trials, as well as in recent meta-analyses on the use of
TAVI in patient at intermediate-risk for surgery.
PMID- 28502733
TI - Reduced anxiety-like behavior in transgenic rats with chronically overproduction
of angiotensin-(1-7): Role of the Mas receptor.
AB - Angiotensin-(1-7) [Ang-(1-7)], a counterregulatory peptide of the renin
angiotensin system (RAS), exerts its cardiovascular and renal functions through
the G-protein-coupled receptor Mas. More recently, Ang-(1-7) has also been
implicated in the control of emotional states related to fear and anxiety. Here,
we tested the hypothesis that transgenic rats overexpressesing Ang-(1-7) (TGR)
show reduced anxiety-like behavior in two distinct animals models, the Elevated
Plus Maze (EPM) and Vogel Conflict Test (VCT). Sprague-Dawley rats (SDs) were
used as controls. In addition, we also verified whether this phenotype depend on
activation of the Mas receptor. In line with our hypothesis, TGR rats showed an
increase in the percentage of time and entries in the open arms of the EPM. There
was also an increase in the number of punished licks in VCT. These phenotypes
were reversed by ICV injection of the Mas receptor antagonist, A779, but not by
the AT2 and MrgD receptor antagonist, PD123319. These results suggest that
chronic elevation of Ang-(1-7) levels results in a phenotype characterized by
reduced anxiety-like behavior, possibly due to higher activation of the Mas
receptor. Therefore, facilitation of the Ang-(1-7)/Mas receptor signaling may be
further investigated as an additional strategy for the treatment of anxiety
related disorders.
PMID- 28502735
TI - Effects of low calcium dialysate on the progression of coronary artery
calcification in hemodialysis patients: An open-label 12-month randomized
clinical trial.
AB - BACKGROUND: The association between the dialysate calcium level and coronary
artery calcification (CAC) has not yet been evaluated in hemodialysis patients.
The objective of this study was to determine whether lowering the dialysate
calcium levels would decrease the progression of coronary artery calcification
(CAC) compared to using standard calcium dialysate. METHODS: We conducted an open
label randomized trial with parallel groups. The patients were randomly assigned
to either 12-month treatment with low calcium dialysate (LCD; 1.25mmol/L, n=36)
or standard calcium dialysate (SCD; 1.5mmol/L, n=40). The primary outcome was the
change in the CAC scores assessed by 64-slice multidetector computed tomography
after 12months. RESULTS: During the treatment period, CAC scores increased in
both groups, especially significant in LCD group (402.5+/-776.8, 580.5+/-1011.9,
P=0.004). When we defined progressors as patients at second and third tertiles of
CAC changes, progressor group had a higher proportion of LCD-treated patients
than SCD-treated patients (P=0.0229). In multivariate analysis, LCD treatment is
a significant risk factor for increase in CAC scores (odds ratio=5.720, 95% CI:
1.219-26.843, P=0.027). CONCLUSIONS: Use of LCD may accelerate the progression of
CAC in patients with chronic hemodialysis over a 12-month period. TRIAL
REGISTRATION: Clinical Research Information Service [Internet]; Osong
(Chungcheongbuk-do): Korea Centers for Disease Control and Prevention, Ministry
of Health and Welfare (Republic of Korea), 2010: KCT0000942. Available from:
https://cris.nih.go.kr/cris/search/search_result_st01_kren.jsp?seq=3572&sLeft=2&t
pe=my.
PMID- 28502736
TI - Positive family history of aortic dissection dramatically increases dissection
risk in family members.
AB - OBJECTIVES: Although family members of patients with aortic dissection (AoD) are
believed to be at higher risk of AoD, the prognostic value of family history (FH)
of aortic dissection (FHAD) in family members of patients with AoD has not been
studied rigorously. We seek examine how much a positive FHAD increases the risk
of developing new aortic dissection (AoD) among first-degree relatives. METHODS:
Patients with AoD at our institution were analyzed for information of FHAD.
Positive FHAD referred to that AoD occurred in index patient and one or more
first-degree relatives. Negative FHAD was defined as the condition in which only
one case of AoD (the index patient) occurred in the family. The age at AoD,
exposure years in adulthood before AoD, and annual probability of AoD among first
degree relatives were compared between patients with negative and positive FHADs.
RESULTS: FHAD was positive in 32 and negative in 68 among the 100 AoD patients
with detailed family history information. Mean age at dissection was 59.9+/
14.7years. Compared to negative FHAD, patients with positive FHAD dissected at
significantly younger age (54.7+/-16.8 vs 62.4+/-13.0years, p=0.013), had more
AoD events in first-degree relatives (2.3+/-0.6 vs 1.0+/-0.0, p<0.001), and
shorter exposure years per AoD event (18.3+/-6.7 vs 43.1+/-8.5, p<0.001). Annual
probability of AoD per first-degree relative was 2.77 times higher in patients
with positive than negative FHADs (0.0100+/-0.0057 vs 0.0036+/-0.0014, p<0.001).
CONCLUSIONS: A positive FHAD confers a significantly increased risk of developing
aortic dissection on family members, with a higher annual probability of aortic
dissection, a shorter duration of "exposure time" before dissection occurs and a
lower mean age at time of dissection.
PMID- 28502738
TI - Maternal emotional feeding practices and adolescent daughters' emotional eating:
Mediating roles of avoidant and preoccupied coping.
AB - The current study examined the link between early childhood emotional feeding and
adolescent girls' emotional eating, using maladaptive coping styles as the
underlying mechanisms mediating these associations. We examined adolescent girls'
and mothers' retrospective reports of emotional feeding during childhood, as well
as adolescent girls' current reports of their coping behaviors (i.e., preoccupied
and avoidant) and emotional eating. Findings showed that adolescent girls' and
mothers' retrospective reports of early emotional feeding were positively
associated with adolescent girls' emotional eating. Preoccupied coping, but not
avoidant coping, mediated the associations between early emotional feeding
(reported by adolescents and mothers) and adolescents' current emotional eating.
In conclusion, findings suggest that early childhood feeding experiences are
linked to the development of maladaptive coping and emotional eating among
adolescent girls.
PMID- 28502737
TI - Gel-free/label-free proteomic, photosynthetic, and biochemical analysis of cowpea
(Vigna unguiculata [L.] Walp.) resistance against Cowpea severe mosaic virus
(CPSMV).
AB - : Cowpea severe mosaic virus (CPSMV) causes significant losses in cowpea (Vigna
unguiculata) production. In this present study biochemical, physiological, and
proteomic analysis were done to identify pathways and defense proteins that are
altered during the incompatible interaction between the cowpea genotype BRS
Marataoa and CPSMV. The leaf protein extracts from mock- (MI) and CPSMV
inoculated plantlets (V) were evaluated at 2 and 6days post-inoculation (DPI).
Data support the assumptions that increases in biochemical (high hydrogen
peroxide, antioxidant enzymes, and secondary compounds) and physiological
responses (high photosynthesis index and chlorophyll content), confirmed by label
free comparative proteomic approach, in which quantitative changes in proteasome
proteins, proteins related to photosynthesis, redox homeostasis, regulation
factors/RNA processing proteins were observed may be implicated in the resistance
of BRS-Marataoa to CPSMV. This pioneering study provides information for the
selection of specific pathways and proteins, altered in this incompatible
relationship, which could be chosen as targets for detailed studies to advance
our understanding of the molecular, physiological, and biochemistry basis of the
resistance mechanism of cowpea and design approachs to engineer plants that are
more productive. BIOLOGICAL SIGNIFICANCE: This is a pioneering study in which an
incompatible relationship between a resistant cowpea and Cowpea severe mosaic
virus (CPSMV) was conducted to comparatively evaluate proteomic profiles by Gel
free/label-free methodology and some physiological and biochemical parameters to
shed light on how a resistant cowpea cultivar deals with the virus attack.
Specific proteins and associated pathways were altered in the cowpea plants
challenged with CPSMV and will contribute to our knowledge on the biological
process tailored by cowpea in response to CPSMV.
PMID- 28502739
TI - The Hunger Games: Using hunger to promote healthy choices in self-control
conflicts.
AB - The majority of existing research and conventional wisdom would advise against
shopping on an empty stomach as hunger is assumed to encourage impulsive choices
that typically lead to self-control failure (i.e., favouring short-term
gratifications at the expense of long-term goals). Nonetheless, through two
studies the current research aims to demonstrate that hungry consumers would not
always be disadvantaged when encountering a self-control conflict involving a
trade-off choice between a healthy vs. a more palatable but unhealthy choice.
Particularly we posit that the choice outcome of the self-control conflict is
dependent on contextual cues, such that hungry consumers with the tendency to
make fast decisions could benefit from following a social proof heuristic
promoting the healthy options. In Study 1, we indeed observed participants' self
reported hunger to be negatively associated with state self-control, but as most
participants generally experienced low levels of hunger we did not observe
apparent effects of hunger on food choice (DV), and correspondingly the potential
influence of the social proof heuristic in moderating the choice outcome.
However, in Study 2 where hunger was manipulated, we found hungry participants
making significantly less healthy choices than satiated participants, but a
social proof heuristic mitigated this effect (i.e., in the presence of social
proof heuristic hungry participants made just as many healthy food choices as
satiated participants; and hungry participants made more healthy choices in the
social proof condition than in the no heuristic condition). These findings
support our approach of providing contextual cues in the environment in order to
work with, rather than against, the impulsivity triggered by hunger to promote
successful self-control behaviours.
PMID- 28502740
TI - Isolation of an insulin-like peptide from the Asian malaria mosquito, Anopheles
stephensi, that acts as a steroidogenic gonadotropin across diverse mosquito
taxa.
AB - Many insulin-like peptides (ILPs) have been identified in insects, yet only a few
were isolated in their native form for structural and functional studies.
Antiserum produced to ILP3 in Aedes aegypti was used in a radioimmunoassay to
monitor the purification of an ILP from heads of adult An. stephensi and
recognized the ILP in other immunoassays. The structure of the purified peptide
matched that predicted for the ILP3 in this species. The native form stimulated
ecdysteroid production by ovaries isolated from non-blood fed females. Synthetic
forms of An. stephensi ILP3 and ILP4 similarly activated this process in a dose
responsive manner. This function was first established for ILP3 and ILP4 homologs
in Aedes aegypti, thus suggesting their structural and functional conservation in
mosquitoes. We tested the extent of conservation by treating ovaries of An.
gambiae, Ae. aegypti, and Culex quinquefasciatus with the An. stephensi ILPs, and
both the native and synthetic ILP3 were stimulatory, as was the ILP4. Taken
together, these results offer the first evidence for ILP functional conservation
across the Anophelinae and Culicinae subfamilies.
PMID- 28502741
TI - High metabolic activity of tissue-nonspecific alkaline phosphatase not only in
young but also in adult bone as demonstrated using a new histochemical detection
protocol.
AB - Tissue-nonspecific alkaline phosphatase (TNAP) is playing a key role in bone
calcification, as has been demonstrated in different mammalian species including
human and rodents. However, to investigate age-related changes during life
history, histochemical demonstration of TNAP is severely hampered, particularly
in the elderly, by technical difficulties associated with sectioning calcified
tissue. Sufficient fixation must precede decalcification since poorly fixed bone
tissue is exposed to the deleterious effects of decalcification reagents. In
order to find a method that would allow cryosectioning of bone without loss of
TNAP activity, we assessed the efficacy of different fixation reagents regarding
the effects on structural integrity and TNAP activity using liver and osseous
tissue from younger and older horses. The results of this study reveal that
glyoxal-based fixatives sufficiently preserved bone tissue for successful
cryosectioning without compromising TNAP activity. The method described combines
the demonstration of TNAP activity with optimal preservation of tissue morphology
in osseous tissue of younger and even of older mammals. As a model species, we
selected horse bones in light of potentially higher similarities to ageing
history and lifelong locomotion in humans as compared to other, mostly smaller,
experimental model species with a much shorter life span and artificial
locomotive activity when kept in cages. This may serve as a basis for future
studies addressing the impact of different life traits in iconic, domestic and
companion animals, which are often patients in veterinary medicine, as well as
for basic research on human physiology and pathologies of the musculoskeletal
system.
PMID- 28502742
TI - Seasonal changes of androgen receptor, estrogen receptors and aromatase
expression in the hippocampus of the wild male ground squirrels (Citellus
dauricus Brandt).
AB - The wild ground squirrel is a typical seasonal breeder whose annual life cycle
can be roughly divided into the breeding season, the post-breeding season and
hibernation. Our previous study has reported the seasonal changes in the
expressions of androgen receptor (AR), estrogen receptors alpha and beta (ERalpha
and ERbeta), and aromatase cytochrome P450 (P450arom) in the hypothalamus of male
wild ground squirrels. To further seek evidence of seasonal expression of steroid
hormone receptors and steroid hormone synthases in other brain regions, we
investigated the protein and mRNA expressions of AR, ERalpha, ERbeta and P450arom
in the hippocampus of the male wild ground squirrels during these different
reproductive periods. Histological observation showed that the number of
pyramidal cells in Cornu Ammonis 1 (CA1) increased in the breeding season. Both
protein and mRNA of AR, ERalpha, ERbeta and P450arom were present in CA1 and CA3
of all seasons. There was significant increment in the immune-signal intensity
and mRNA level of AR and ERalpha during the pre-hibernation, whereas those of
ERbeta and P450arom were higher during the post-breeding season. In addition, the
profile of plasma testosterone concentration showed the nadir in the post
breeding season, a marked elevation in the pre-hibernation, and the summit in the
breeding season. These findings suggested that the hippocampus may be a direct
target of androgen and estrogen; androgen may play important regulatory roles
through its receptor and/or the aromatized estrogen in the hippocampus of the
wild male ground squirrels.
PMID- 28502743
TI - Reply to Garcia J. et al.
PMID- 28502744
TI - Effect of high-dose sodium selenite in cardiac surgery patients: A randomized
controlled bi-center trial.
AB - BACKGROUND & AIMS: Cardiac surgery is accompanied by oxidative stress and
systemic inflammatory response, which may be associated with organ dysfunction
and increased mortality. Selenium and selenoenzymes are important constituents of
anti-oxidative defense. We hypothesized that high-dose sodium selenite
supplementation can attenuate the postoperative inflammation and might,
therefore, improve clinical outcome. METHODS: Randomized, placebo-controlled,
double-blinded, bi-center study on 411 adult patients undergoing elective cardiac
surgery. Patients received an intravenous bolus of 4000 MUg selenium (in the form
of sodium selenite) or placebo after induction of anesthesia and 1000 MUg/d
selenium or placebo during their intensive care unit (ICU) stay. Primary outcome
measure was the Sequential Organ Failure Assessment (SOFA) score on the second
postoperative day. Secondary endpoints included the change in perioperative
selenium levels, change of inflammatory and cardiac markers, use of vasoactive
medication, incidence of acute kidney injury, ICU and hospital length of stay,
and mortality. RESULTS: The perioperative administration of high-dose sodium
selenite prevented the postoperative drop of blood and serum selenium levels,
reduced the number of patients depending on postoperative vasoactive support but
failed to reduce the postoperative SOFA score and its related organ-specific
scores compared to placebo. Except for an increase of postoperative procalcitonin
and bilirubin levels in the sodium selenite group, other inflammatory markers,
organ function variables and clinical endpoints remained unchanged. CONCLUSIONS:
The perioperative administration of high-dose sodium selenite in cardiac surgery
patients prevented the postoperative fall of blood selenium levels and reduced
the need for postoperative vasoactive support by a yet unknown mechanism. TRIAL
REGISTRATION: Registered under ClinicalTrials.gov Identifier no. NCT01141556.
PMID- 28502745
TI - Pi5 and Pi6, two undescribed peptides from the venom of the scorpion Pandinus
imperator and their effects on K+-channels.
AB - This work reports the isolation, chemical and functional characterization of two
previously unknown peptides purified from the venom of the scorpion Pandinus
imperator, denominated Pi5 and Pi6. Pi5 is a classical K+-channel blocking
peptide containing 33 amino acid residues with 4 disulfide bonds. It is the first
member of a new subfamily, here defined by the systematic number alpha-KTx 24.1.
Pi6 is a peptide of unknown real function, containing only two disulfide bonds
and 28 amino acid residues, but showing sequence similarities to the kappa-family
of K-channel toxins. The systematic number assigned is kappa-KTx2.9. The function
of both peptides was assayed on Drosophila Shab and Shaker K+-channels, as well
as four different subtypes of voltage-dependent K+-channels: hKv1.1, hKv1.2,
hKv1.3 and hKv1.4. The electrophysiological assays showed that Pi5 inhibited
Shaker B, hKv1.1, hKv1.2 and hKv1.3 channels with Kd = 540 nM, Kd = 92 nM and Kd
= 77 nM, respectively, other studied channels were not affected. Of the channels
tested only hKv1.2 and hKv1.3 were inhibited at 100 nM concentration of Pi6, the
remaining current fractions were 68% and 77%, respectively. Thus, Pi5 and Pi6 are
high nanomolar affinity non-selective blockers of hKv1.2 and hKv1.3 channels.
PMID- 28502747
TI - Chicken egg fetal liver DNA and histopathologic effects of structurally diverse
carcinogens and non-carcinogens.
AB - Chicken egg fetal livers were evaluated for histopathological changes produced by
four genotoxic hepatocarcinogens: 2-acetylaminofluorene (AAF), aflatoxin B1
(AFB1), benzo[a]pyrene (BaP), diethylnitrosamine (DEN); four structurally related
non- or weakly- carcinogenic comparators: fluorene (FLU), aflatoxin B2 (AFB2),
benzo[e]pyrene (BeP), N-nitrosodiethanolamine (NDELA); two epigenetic
hepatocarcinogens: clofibric acid (CFA), phenobarbital (PB); and the non
carcinogen, D-mannitol (MAN). CFA, PB and MAN were also assessed for formation of
DNA adducts using the 32P nucleotide postlabeling (NPL) assay and for DNA breaks
using the comet assay. CFA was also assessed in enhanced comet assay for
oxidative DNA damage induction. Eggs were dosed on days 9- 11 of incubation. For
genotoxicity evaluation, livers were collected 3h after the last dose. Liver
qualitative histopathology assessment was performed on days 12 and 18 of
incubation. CFA was negative for DNA adducts but yielded clear evidence of DNA
breaks due to oxidative stress. PB and MAN produced no DNA adducts or breaks.
Liver to body weight ratios were not affected in most groups, but were decreased
in DEN groups, and increased after PB dosing. Livers from control groups, FLU,
AFB2, BeP, NDELA, CFA, and MAN groups, displayed a typical hepatocellular
trabecular pattern at both time points. In contrast, the four genotoxic
carcinogens induced time- and dose- related interference with fetal liver cell
processes of proliferation, migration and differentiation, leading to
hepatocellular and cholangiocellular pleomorphic dysplasia and re-(de-)
differentiation with distortion of the trabecular pattern. In addition, dosing
with the high dose of DEN produced gallbladder agenesis. PB induced
hepatocellular hypertrophy, interference with migration, expressed as distortion
of the trabecular pattern, and a moderate cholangiocellular dysplasia. In
summary, histopathological analysis of chicken fetal livers revealed
developmental anomalies, as well as genotoxicity-induced and, in the case of PB,
adaptive morphological changes. Thus, the model provides histopathological
outcomes of molecular effects.
PMID- 28502748
TI - Cytochrome P450 diversity in the tree of life.
AB - Sequencing in all areas of the tree of life has produced >300,000 cytochrome P450
(CYP) sequences that have been mined and collected. Nomenclature has been
assigned to >41,000 CYP sequences and the majority of the remainder has been
sorted by BLAST searches into clans, families and subfamilies in preparation for
naming. The P450 sequence space is being systematically explored and filled in.
Well-studied groups like vertebrates are covered in greater depth while new
insights are being added into uncharted territories like horseshoe crab (Limulus
polyphemus), tardigrades (Hypsibius dujardini), velvet worm
(Euperipatoides_rowelli), and basal land plants like hornworts, liverworts and
mosses. CYPs from the fungi, one of the most diverse groups, are being explored
and organized as nearly 800 fungal species are now sequenced. The CYP clan
structure in fungi is emerging with 805 CYP families sorting into 32 CYP clans.
>3000 bacterial sequences are named, mostly from terrestrial or freshwater
sources. Of 18,379 bacterial sequences downloaded from the CYPED database, all
are >43% identical to named CYPs. Therefore, they fit in the 602 named P450
prokaryotic families. Diversity in this group is becoming saturated, however 25%
of 3305 seawater bacterial P450s did not match known P450 families, indicating
marine bacterial CYPs are not as well sampled as land/freshwater based bacterial
CYPs. Future sequencing plans of the Genome 10K project, i5k and GIGA (Global
Invertebrate Genomics Alliance) are expected to produce more than one million
cytochrome P450 sequences by 2020. This article is part of a Special Issue
entitled: Cytochrome P450 biodiversity and biotechnology, edited by Erika
Plettner, Gianfranco Gilardi, Luet Wong, Vlada Urlacher, Jared Goldstone.
PMID- 28502750
TI - Cervical length cut-off in twin pregnancy and preterm labor risk assessment
algorithm: call for action.
PMID- 28502746
TI - Diminishing fear: Optogenetic approach toward understanding neural circuits of
fear control.
AB - Understanding complex behavioral processes, both learned and innate, requires
detailed characterization of the principles governing signal flow in
corresponding neural circuits. Previous studies were hampered by the lack of
appropriate tools needed to address the complexities of behavior-driving micro-
and macrocircuits. The development and implementation of optogenetic
methodologies revolutionized the field of behavioral neuroscience, allowing
precise spatiotemporal control of specific, genetically defined neuronal
populations and their functional connectivity both in vivo and ex vivo, thus
providing unprecedented insights into the cellular and network-level mechanisms
contributing to behavior. Here, we review recent pioneering advances in
behavioral studies with optogenetic tools, focusing on mechanisms of fear-related
behavioral processes with an emphasis on approaches which could be used to
suppress fear when it is pathologically expressed. We also discuss limitations of
these methodologies as well as review new technological developments which could
be used in future mechanistic studies of fear behavior.
PMID- 28502749
TI - A relevant IgE-reactive 28kDa protein identified from Salsola kali pollen extract
by proteomics is a natural degradation product of an integral 47kDa
polygalaturonase.
AB - A highly prevalent IgE-binding protein band of 28kDa is observed when Salsola
kali pollen extract is incubated with individual sera from Amaranthaceae pollen
sensitized patients. By an immunoproteomic analysis of S. kali pollen extract, we
identified this protein band as an allergenic polygalacturonase enzyme. The
allergen, named Sal k 6, exhibits a pI of 7.14 and a molecular mass of
39,554.2Da. It presents similarities to Platanaceae, Poaceae, and Cupressaceae
allergenic polygalacturonases. cDNA-encoding sequence was subcloned into the
pET41b vector and produced in bacteria as a His-tag fusion recombinant protein.
The far-UV CD spectrum determined that rSal k 6 was folded. Immunostaining of the
S. kali pollen protein extract with a rSal k 6-specific pAb and LC-MS/MS
proteomic analyses confirmed the co-existence of the 28kDa band together with an
allergenic band of about 47kDa in the pollen extract. Therefore, the 28kDa was
assigned as a natural degradation product of the 47kDa integral
polygalacturonase. The IgE-binding inhibition to S. kali pollen extract using
rSal k 6 as inhibitor showed that signals directed to both protein bands of 28
and 47kDa were completely abrogated. The average prevalence of rSal k 6 among the
three populations analyzed was 30%, with values correlating well with the levels
of grains/m3 of Amaranthaceae pollen. Sal k 6 shares IgE epitopes with Oleaceae
members (Fraxinus excelsior, Olea europaea and Syringa vulgaris), with IgE
inhibition values ranging from 20% to 60%, respectively. No IgE-inhibition was
observed with plant-derived food extracts.
PMID- 28502751
TI - Comment on: Predicting the difficulty of operative vaginal delivery by ultrasound
measurement of fetal head station.
PMID- 28502752
TI - Reply.
PMID- 28502753
TI - Reply.
PMID- 28502754
TI - Lifetime cancer risk with progestin and estrogen oral contraceptives and hormone
therapy.
PMID- 28502755
TI - Comment on: A randomized clinical trial of exercise during pregnancy to prevent
gestational diabetes mellitus and improve pregnancy outcome in overweight and
obese pregnant women.
PMID- 28502756
TI - Reply.
PMID- 28502757
TI - The placental imprinted DLK1-DIO3 domain: a new link to prenatal and postnatal
growth in humans.
AB - BACKGROUND: The developmentally important DLK1-DIO3 imprinted domain on human
chromosome 14 is regulated by 2 differentially methylated regions, the intergenic
differentially methylated region and the MEG3 differentially methylated region.
OBJECTIVE: The aim was to determine the natural variation in DNA methylation at
these differentially methylated regions in human placentas, and to determine its
link to gene expression levels at the domain. The second goal was to explore
whether the domain's methylation and gene expression correlate with prenatal and
early postnatal growth of the conceptus. STUDY DESIGN: Using pyrosequencing, we
determined methylation levels at CpG dinucleotides across the 2 regulatory
differentially methylated regions in placentas from 91 healthy mothers. At birth,
placentas and infants were weighed (gestational age 39 +/- 1 weeks; birthweight
SD score 0.1 +/- 0.8) and placental biopsies were collected. RNA expression was
quantitated by real-time polymerase chain reaction. Infants' weights and lengths
were followed up monthly during the first year. RESULTS: Methylation levels at
the 2 regulatory differentially methylated regions were linked and varied
considerably between placentas. MEG3 promoter differentially methylated region
methylation correlated negatively with weight increase (beta = -0.406, P = .001,
R2 = 0.206) and length increase (beta = -0.363, P = .002, R2 = 0.230) during the
first postnatal year. The methylation level of the intergenic differentially
methylated region correlated with DIO3 expression (beta = 0.313, P = .032, R2 =
0.152). Furthermore, the expression of both DIO3 and RTL1 (both imprinted genes
within the DLK1-DIO3 domain) was negatively associated with birthweight (beta =
0.331, P = .002, R2 = 0.165; and beta = -0.307, P = .005, R2 = 0.159,
respectively). RTL1 expression, in addition, was negatively linked to birth
length (beta = -0.306, P = .007, R2 = 0.162). CONCLUSION: Our combined findings
strongly suggest that placental DNA methylation at the DLK1-DIO3 domain's
intergenic differentially methylated region and MEG3 promoter differentially
methylated region relates to measures of early human growth, and may thus
contribute to its control.
PMID- 28502759
TI - Reply.
PMID- 28502758
TI - The impact of postpartum hemorrhage on hospital length of stay and inpatient
mortality: a National Inpatient Sample-based analysis.
AB - BACKGROUND: Postpartum hemorrhage is a major cause of maternal morbidity and
mortality, but the association between postpartum hemorrhage and hospital length
of stay has not been rigorously investigated. OBJECTIVE: We explored the impact
of postpartum hemorrhage on hospital length of stay and inpatient mortality, as
these outcomes have both clinical and economic significance. STUDY DESIGN: We
performed a retrospective analysis using data from the National Inpatient Sample
database during the 2012 through 2013 time period. Deliveries were classified as
postpartum hemorrhage due to uterine atony, nonatonic postpartum hemorrhage, or
not complicated by postpartum hemorrhage (nonpostpartum hemorrhage). Average
length of stay and inpatient mortality rates were compared between groups.
RESULTS: Over the study interval, postpartum hemorrhage occurred in 3% of
deliveries. Among deliveries complicated by postpartum hemorrhage, 76.6% were
attributed to uterine atony and 23.4% were nonatonic. Women with nonatonic
postpartum hemorrhage had the highest average length of stay (3.67 days) followed
by atonic postpartum hemorrhage (2.98 days) and nonpostpartum hemorrhage (2.63
days); P < .001, all comparisons. Inpatient mortality rate of nonatonic
postpartum hemorrhage over the entire study period was 104 per 100,000 compared
to 019 per 100,000 for atonic postpartum hemorrhage and 3 per 100,000 for
nonpostpartum hemorrhage deliveries (P < .001). CONCLUSION: From 2012 through
2013, women with postpartum hemorrhage experienced significantly longer length of
stay and higher inpatient mortality rates than women without postpartum
hemorrhage, largely attributable to nonatonic causes of postpartum hemorrhage. As
hospital length of stay and inpatient mortality are important outcomes from both
clinical and societal perspectives, interventions to reduce morbidity and
mortality related to postpartum hemorrhage may simultaneously facilitate delivery
of more cost-effective care and improve both maternal and population health.
PMID- 28502761
TI - Delayed admission to ICU in acute respiratory failure: Critical time for critical
conditions.
PMID- 28502760
TI - Patterns of gestational weight gain and birthweight outcomes in the Eunice
Kennedy Shriver National Institute of Child Health and Human Development Fetal
Growth Studies-Singletons: a prospective study.
AB - BACKGROUND: Inadequate or excessive total gestational weight gain is associated
with increased risks of small- and large-for-gestational-age births,
respectively, but evidence is sparse regarding overall and trimester-specific
patterns of gestational weight gain in relation to these risks. Characterizing
the interrelationship between patterns of gestational weight gain across
trimesters can reveal whether the trajectory of gestational weight gain in the
first trimester sets the path for gestational weight gain in subsequent
trimesters, thereby serving as an early marker for at-risk pregnancies.
OBJECTIVE: We sought to describe overall trajectories of gestational weight gain
across gestation and assess the risk of adverse birthweight outcomes associated
with the overall trajectory and whether the timing of gestational weight gain
(first vs second/third trimester) is differentially associated with adverse
outcomes. STUDY DESIGN: We conducted a secondary analysis of a prospective cohort
of 2802 singleton pregnancies from 12 US prenatal centers (2009 through 2013).
Small and large for gestational age were calculated using sex-specific
birthweight references <5th, <10th, or >=90th percentiles, respectively. At each
of the research visits, women's weight was measured following a standardized
anthropometric protocol. Maternal weight at antenatal clinical visits was also
abstracted from the prenatal records. Semiparametric, group-based, latent class,
trajectory models estimated overall gestational weight gain and separate first-
and second-/third-trimester trajectories to assess tracking. Robust Poisson
regression was used to estimate the relative risk of small- and large-for
gestational-age outcomes by the probability of trajectory membership. We tested
whether relationships were modified by prepregnancy body mass index. RESULTS:
There were 2779 women with a mean of 15 (SD 5) weights measured across gestation.
Four distinct gestational weight gain trajectories were identified based on the
lowest Bayesian information criterion value, classifying 10.0%, 41.8%, 39.2%, and
9.0% of the population from lowest to highest weight gain trajectories, with an
inflection at 14 weeks. The average rate in each trajectory group from lowest to
highest for 0-<14 weeks was -0.20, 0.04, 0.21, and 0.52 kg/wk and for 14-39 weeks
was 0.29, 0.48, 0.63, and 0.79 kg/wk, respectively; the second lowest gaining
trajectory resembled the Institute of Medicine recommendations and was designated
as the reference with the other trajectories classified as low, moderate-high, or
high. Accuracy of assignment was assessed and found to be high (median posterior
probability 0.99, interquartile range 0.99-1.00). Compared with the referent
trajectory, a low overall trajectory, but not other trajectories, was associated
with a 1.55-fold (95% confidence interval, 1.06-2.25) and 1.58-fold (95%
confidence interval, 0.88-2.82) increased risk of small-for-gestational-age <10th
and <5th, respectively, while a moderate-high and high trajectory were associated
with a 1.78-fold (95% confidence interval, 1.31-2.41) and 2.45-fold (95%
confidence interval, 1.66-3.61) increased risk of large for gestational age,
respectively. In a separate analysis investigating whether early (<14 weeks)
gestational weight gain tracked with later (>=14 weeks) gestational weight gain,
only 49% (n = 127) of women in the low first-trimester trajectory group continued
as low in the second/third trimester, and had a 1.59-fold increased risk of small
for gestational age; for the other 51% (n = 129) of women without a subsequently
low second-/third-trimester gestational weight gain trajectory, there was no
increased risk of small for gestational age (relative risk, 0.75; 95% confidence
interval, 0.47-1.38). Prepregnancy body mass index did not modify the association
between gestational weight gain trajectory and small for gestational age (P =
0.52) or large for gestational age (P = .69). CONCLUSION: Our findings are
reassuring for women who experience weight loss or excessive weight gain in the
first trimester; however, the risk of small or large for gestational age is
significantly increased if women gain weight below or above the reference
trajectory in the second/third trimester.
PMID- 28502762
TI - Clear cell odontogenic carcinoma, diagnostic difficulties. A case report.
AB - INTRODUCTION: Clear cell odontogenic carcinoma (COCC) is a rare tumor described
by Hansen et al. in 1985. The clinical and radiological manifestations are
multiple and the diagnosis is histological. OBSERVATION: A 64-year-old patient
consulted us for a right mandibular osteolytic lesion associated to a homolateral
labial hypoesthesia. A biopsy was performed under local anesthesia. Histology was
consistent with a metastatic lesion of clear kidney cell carcinoma, COCC, or
odontogenic squamous tumor. Additional tests eliminated a metastatic lesion. A
wide excision of the lesion by hemi-mandibulectomy associated with lymph node
dissection and reconstruction by a fibula osteoseptocutaneous flap was performed.
Presence of a fission of the EWSR1 gene on the histological examination of the
surgical specimen made the diagnosis of COCC. DISCUSSION: Our observation
illustrates the difficulty of diagnosing COCC. The new contribution of the
cytogenetic techniques such as FISH-type techniques makes possible the
improvement of the diagnosis.
PMID- 28502763
TI - Osteomyelitis of the jaws: A retrospective series of 40 patients.
AB - INTRODUCTION: The caseload of jaw osteomyelitis seem to have decreased
considerably over the last fifty years thanks to the progress of oral hygiene,
the appearance and the use of antibiotics, and early screening. 'Limited
osteitis' remains frequent in general practice (alveolitis after dental
extraction), but osteomyelitis is much rarer as evidenced by the lack of current
literature and the low number of reported patients in the published series. The
aim of this study was to analyze retrospectively all the cases of maxillo
mandibular osteomyelitis treated in a large academic department of Stomatology
and Maxillofacial Surgery over a period of 6 years and to compare the results to
data from the literature. MATERIAL AND METHOD: All patients diagnosed with
maxillo-mandibular osteomyelitis by one of the staff surgeons between January
2009 and December 2015 was included. An epidemiological record (sex, age, ethnic
background, risk factors, clinical, origin of disease, imaging and biology,
treatments and progression) were collected for each patient. Osteomyelitis cases
were classified according to the Zurich Classification System. Results were
compared to data from the literature. RESULTS: Forty patients were retained.
Three presented acute osteomyelitis, 26 secondary chronic osteomyelitis and 11 a
primary chronic osteomyelitis. Osteomyelitis affected predominantly the mandible
(87%). Dental origin was found in 90% of cases. Nine patients (22.5%) recovered
and 29 (90%) were clinically improved. Ten of the 11 patients with primary
chronic osteomyelitis were improved. DISCUSSION: This cohort study is one of the
largest series currently available and presents results comparable to those of
the literature of the last 25 years.
PMID- 28502764
TI - Cryptic speciation and gene flow in a migratory songbird Species Complex:
Insights from the Red-Eyed Vireo (Vireo olivaceus).
AB - Migratory species that alternate between sympatry and allopatry over the course
of an annual cycle are promising subjects for studies seeking to understand the
process of speciation in the absence of strict geographic isolation. Here we
sought to identify cryptic species and assess rates of gene flow in a clade of
neotropical migrant songbirds in which geography and taxonomy are currently out
of sync: the Red-Eyed Vireo (V. olivaceus) Species Complex. Phylogenetic,
clustering, and statistical species delimitation analyses found that V.
olivaceusincludes two non-sister lineages migrating in opposite directions across
the equator. Analyses of gene flow identified low levels of introgression between
two species pairs, but none between northern and southern olivaceus. We also
identified substantial well-supported conflicts between nuclear and mitochondrial
topologies. Although the geographic distribution of mito-nuclear discordance is
suggestive of hybridization and mitochondrial capture, we found no evidence of
introgression in the nuclear genome of populations with discordant mitochondrial
gene trees. Our study finds that species boundaries match breeding range and
migratory phenology rather than the existing taxonomy in this group, and
demonstrates the utility of genomic data in inferring species boundaries in
recently diverged clades.
PMID- 28502765
TI - Biogeographic links between southern Atlantic Forest and western South America:
Rediscovery, re-description, and phylogenetic relationships of two rare montane
anole lizards from Brazil.
AB - Data on species ranges and phylogenetic relationships are key in historical
biogeographical inference. In South America, our understanding of the
evolutionary processes that underlie biodiversity patterns varies greatly across
regions. Little is known, for instance, about the drivers of high endemism in the
southern montane region of the Atlantic Rainforest. In this region, former
biogeographic connections with other South American ecosystems have been invoked
to explain the phylogenetic affinities of a number of endemic taxa. This may also
be the case of the montane anole lizards Anolis nasofrontalis and A.
pseudotigrinus, known from few specimens collected more than 40years ago. We
combine new genetic data with published sequences of species in the Dactyloa
clade of Anolis to investigate the phylogenetic relationships of A. nasofrontalis
and A. pseudotigrinus, as well as estimate divergence times from their closest
relatives. Based on newly sampled and previously overlooked specimens, we provide
a taxonomic re-description of those two taxa. Our phylogenetic analysis recovered
six main clades within Dactyloa, five of which were previously referred to as
species series (aequatorialis, heterodermus, latifrons, punctatus, roquet). A
sixth clade clustered A. nasofrontalis and A. pseudotigrinus with A. dissimilis
from western Amazonia, A. calimae from the Andes, A. neblininus from the Guiana
Shield, and two undescribed Andean taxa. We therefore define a sixth species
series within Dactyloa: the neblininus series. Close phylogenetic relationships
between highly disjunct, narrowly-distributed anoles suggest that patches of
suitable habitat connected the southern Atlantic Forest to western South America
during the Miocene, in agreement with the age of former connections between the
central Andes and the Brazilian Shield as a result of Andean orogeny. The data
also support the view of recurrent evolution (or loss) of a twig anole-like
phenotype in mainland anoles, in apparent association with the occurrence in
montane settings. Our findings stress the value of complementary genetic sampling
efforts across South American countries to advance studies of mainland anole
taxonomy and evolution.
PMID- 28502766
TI - Anterior cingulate serotonin 1B receptor binding is associated with emotional
response inhibition.
AB - Serotonin has a well-established role in emotional processing and is a key
neurotransmitter in impulsive aggression, presumably by facilitating response
inhibition and regulating subcortical reactivity to aversive stimuli. In this
study 44 men, of whom 19 were violent offenders and 25 were non-offender
controls, completed an emotional Go/NoGo task requiring inhibition of prepotent
motor responses to emotional facial expressions. We also measured cerebral
serotonin 1B receptor (5-HT1BR) binding with [11C]AZ10419369 positron emission
tomography within regions of the frontal cortex. We hypothesized that 5-HT1BR
would be positively associated with false alarms (failures to inhibit nogo
responses) in the context of aversive (angry and fearful) facial expressions.
Across groups, we found that frontal cortex 5-HT1BR binding was positively
correlated with false alarms when angry faces were go stimuli and neutral faces
were nogo stimuli (p = 0.05, corrected alpha = 0.0125), but not with false alarms
for non-emotional stimuli (failures to inhibit geometric figures). A posthoc
analysis revealed the strongest association in anterior cingulate cortex (p =
0.006). In summary, 5-HT1BRs in the anterior cingulate are involved in
withholding a prepotent response in the context of angry faces. Our findings
suggest that serotonin modulates response inhibition in the context of certain
emotional stimuli.
PMID- 28502767
TI - Modulating angiogenesis with integrin-targeted nanomedicines.
AB - Targeting angiogenesis-related pathologies, which include tumorigenesis and
metastatic processes, has become an attractive strategy for the development of
efficient guided nanomedicines. In this respect, integrins are cell-adhesion
molecules involved in angiogenesis signaling pathways and are overexpressed in
many angiogenic processes. Therefore, they represent specific biomarkers not only
to monitor disease progression but also to rationally design targeted
nanomedicines. Arginine-glycine-aspartic (RGD) containing peptides that bind to
specific integrins have been widely utilized to provide ligand-mediated targeting
capabilities to small molecules, peptides, proteins, and antibodies, as well as
to drug/imaging agent-containing nanomedicines, with the final aim of maximizing
their therapeutic index. Within this review, we aim to cover recent and relevant
examples of different integrin-assisted nanosystems including polymeric
nanoconstructs, liposomes, and inorganic nanoparticles applied in drug/gene
therapy as well as imaging and theranostics. We will also critically address the
overall benefits of integrin-targeting.
PMID- 28502769
TI - Tracing the Enterococci from Paleozoic Origins to the Hospital.
AB - We examined the evolutionary history of leading multidrug resistant hospital
pathogens, the enterococci, to their origin hundreds of millions of years ago.
Our goal was to understand why, among the vast diversity of gut flora,
enterococci are so well adapted to the modern hospital environment. Molecular
clock estimation, together with analysis of their environmental distribution,
phenotypic diversity, and concordance with host fossil records, place the origins
of the enterococci around the time of animal terrestrialization, 425-500 mya.
Speciation appears to parallel the diversification of hosts, including the rapid
emergence of new enterococcal species following the End Permian Extinction. Major
drivers of speciation include changing carbohydrate availability in the host gut.
Life on land would have selected for the precise traits that now allow pathogenic
enterococci to survive desiccation, starvation, and disinfection in the modern
hospital, foreordaining their emergence as leading hospital pathogens.
PMID- 28502770
TI - An Atomic Structure of the Human Spliceosome.
AB - Mechanistic understanding of pre-mRNA splicing requires detailed structural
information on various states of the spliceosome. Here we report the cryo
electron microscopy (cryo-EM) structure of the human spliceosome just before exon
ligation (the C* complex) at an average resolution of 3.76 A. The splicing factor
Prp17 stabilizes the active site conformation. The step II factor Slu7 adopts an
extended conformation, binds Prp8 and Cwc22, and is poised for selection of the
3'-splice site. Remarkably, the intron lariat traverses through a positively
charged central channel of RBM22; this unusual organization suggests mechanisms
of intron recruitment, confinement, and release. The protein PRKRIP1 forms a 100
A alpha helix linking the distant U2 snRNP to the catalytic center. A 35-residue
fragment of the ATPase/helicase Prp22 latches onto Prp8, and the quaternary exon
junction complex (EJC) recognizes upstream 5'-exon sequences and associates with
Cwc22 and the GTPase Snu114. These structural features reveal important
mechanistic insights into exon ligation.
PMID- 28502773
TI - Phosphorylation of alphaB-crystallin in the myocardium: Analysis of relations
with aging and cardiomyopathy.
AB - Phosphorylation is a major post-translational modification of alphaB-crystallin
(CryaB) and determines this protein's chaperone activity, intracellular
distribution, translocation, and cytoprotective functions. Phosphorylation of
CryaB manifests itself as either beneficial or deleterious consequences depending
on the extent of phosphorylation and interaction with the cytoskeleton. Herein,
for the first time, we compared the age-related alterations of the expression and
phosphorylation (on Ser59: pS59) of CryaB in the myocardium of Wistar and
senescence-accelerated OXYS rats. The latters, as we demonstrated here, develop
cardiomyopathy by the age of 12 months against the background of hypertension.
Rats at the age of 20 days, 3, 12, and 24 months were used. The expression of
CryaB mRNA (studied by RT-PCR) and of the CryaB protein (analyzed by western
blotting) increased with age in the myocardium of both Wistar and OXYS rats, but
only at the age of 24 months did their levels become lower in OXYS rats.
Phosphorylation of CryaB increased with age in all rats. There was no association
of cardiomyopathy with the pS59-CryaB amount in the detergent-soluble fraction
either. Moreover, immunostaining of the myocardium revealed that the amount of
pS59-CryaB was greater in OXYS rats than in the control animals. This phenomenon
was the result of translocation of pS59-CryaB from the detergent-soluble protein
fraction to the detergent-insoluble one. The amount of pS59-CryaB in striated
sarcomeres (detergent-insoluble) of the myocardium increased with age in both
strains but faster in the myocardium of OXYS rats, and its accumulation preceded
the development of cardiomyopathy. Translocation of phosphorylated CryaB to
sarcomeres affects functional and structural properties (of cardiomyocytes) that
are crucial for contractile function and myofibrillar organization and may be an
important component of an endogenous mechanism of aging of the myocardium.
PMID- 28502772
TI - Representations of Novelty and Familiarity in a Mushroom Body Compartment.
AB - Animals exhibit a behavioral response to novel sensory stimuli about which they
have no prior knowledge. We have examined the neural and behavioral correlates of
novelty and familiarity in the olfactory system of Drosophila. Novel odors elicit
strong activity in output neurons (MBONs) of the alpha'3 compartment of the
mushroom body that is rapidly suppressed upon repeated exposure to the same odor.
This transition in neural activity upon familiarization requires odor-evoked
activity in the dopaminergic neuron innervating this compartment. Moreover,
exposure of a fly to novel odors evokes an alerting response that can also be
elicited by optogenetic activation of alpha'3 MBONs. Silencing these MBONs
eliminates the alerting behavior. These data suggest that the alpha'3 compartment
plays a causal role in the behavioral response to novel and familiar stimuli as a
consequence of dopamine-mediated plasticity at the Kenyon cell-MBONalpha'3
synapse.
PMID- 28502774
TI - Latitudinal and age-specific patterns of larval mortality in the damselfly Lestes
sponsa: Senescence before maturity?
AB - Latitudinal differences in life history traits driven by differences in seasonal
time constraints have been widely documented. Yet, latitudinal patterns in (age
specific) mortality rates have been poorly studied. Here, we studied latitudinal
differences in pre-adult age-specific mortality patterns in the strictly
univoltine damselfly Lestes sponsa. We compared individuals from three latitudes
reared from the egg stage in the laboratory at temperatures and photoperiods
simulating those at the latitude of origin (main experiment) and under common
garden conditions at a fixed temperature and photoperiod (supplementary
experiment). Results from the main experiment showed that the high-latitude
population exhibited higher mortality rates than the central and southern
populations, likely reflecting a cost of their faster development. Age-specific
mortality patterns, also indicated higher ageing rates in the high-latitude
compared to the low-latitude population, which likely had a genetic basis. The
strong within-population variation in hatching dates in the low-latitude
population caused variation in mortality rates; individuals that hatched later
showed higher mortality rates presumably due to their shorter development times
compared to larvae that hatched earlier. In both experiments, larvae from all
three latitudes showed accelerated mortality rates with age, which is consistent
with a pattern of senescence before adulthood.
PMID- 28502771
TI - Metabolic Phenotypes of Response to Vaccination in Humans.
AB - Herpes zoster (shingles) causes significant morbidity in immune compromised hosts
and older adults. Whereas a vaccine is available for prevention of shingles, its
efficacy declines with age. To help to understand the mechanisms driving vaccinal
responses, we constructed a multiscale, multifactorial response network (MMRN) of
immunity in healthy young and older adults immunized with the live attenuated
shingles vaccine Zostavax. Vaccination induces robust antigen-specific antibody,
plasmablasts, and CD4+ T cells yet limited CD8+ T cell and antiviral responses.
The MMRN reveals striking associations between orthogonal datasets, such as
transcriptomic and metabolomics signatures, cell populations, and cytokine
levels, and identifies immune and metabolic correlates of vaccine immunity.
Networks associated with inositol phosphate, glycerophospholipids, and sterol
metabolism are tightly coupled with immunity. Critically, the sterol regulatory
binding protein 1 and its targets are key integrators of antibody and T
follicular cell responses. Our approach is broadly applicable to study human
immunity and can help to identify predictors of efficacy as well as mechanisms
controlling immunity to vaccination.
PMID- 28502775
TI - On the functional order of binocular rivalry and blind spot filling-in.
AB - Binocular rivalry is an important phenomenon for understanding the mechanisms of
visual awareness. Here we assessed the functional locus of binocular rivalry
relative to blind spot filling-in, which is thought to transpire in V1, thus
providing a reference point for assessing the locus of rivalry. We conducted two
experiments to explore the functional order of binocular rivalry and blind spot
filling-in. Experiment 1 examined if the information filled-in at the blind spot
can engage in rivalry with a physical stimulus at the corresponding location in
the fellow eye. Participants' perceptual reports showed no difference between
this condition and a condition where filling-in was precluded by presenting the
same stimuli away from the blind spot, suggesting that the rivalry process is not
influenced by any filling-in that might occur. In Experiment 2, we presented the
fellow eye's stimulus directly in rivalry with the 'inducer' stimulus that
surrounds the blind spot, and compared it with two control conditions away from
the blind spot: one involving a ring physically identical to the inducer, and one
involving a disc that resembled the filled-in percept. Perceptual reports in the
blind spot condition resembled those in the 'ring' condition, more than those in
the latter, 'disc' condition, indicating that a perceptually suppressed inducer
does not engender filling-in. Thus, our behavioral data suggest binocular rivalry
functionally precedes blind spot filling-in. We conjecture that the neural
substrate of binocular rivalry suppression includes processing stages at or
before V1.
PMID- 28502776
TI - Dried plum and chokeberry ameliorate d-galactose-induced aging in mice by
regulation of Pl3k/Akt-mediated Nrf2 and Nf-kB pathways.
PMID- 28502777
TI - Peripheral muscle fatigue in hospitalised geriatric patients is associated with
circulating markers of inflammation.
AB - Geriatric patients with acute infection show increased muscle weakness and
fatigability but the relative contribution of central and peripheral factors is
unclear. Hospitalised patients with acute infection (82+/-6years, N=10) and
community-dwelling controls (76+/-6years, N=19) sustained a maximal voluntary
isometric contraction of the M. Adductor Pollicis until strength dropped to 50%
of its maximal value. Voluntary muscle activation (VA) was assessed before and at
the end of the fatigue protocol using twitch interpolation method and muscle
activity was monitored using surface electromyography. Twenty-five circulating
inflammatory biomarkers were determined. At pre-fatigue, no significant
difference in VA was found between groups. VA decreased to similar levels (~50%)
at the end of the fatigue protocol with no association with inflammatory
biomarkers. In geriatric patients, muscle activity decreased significantly
(p<0.05) during the fatigue protocol, whereas it increased in the controls
(time*group interaction p<0.05). The decrease in muscle activity was
significantly related to higher levels of inflammation. Although slower muscle
contraction and relaxation were significantly related to higher levels of
inflammation, no statistical differences were found between groups. Our results
confirm that muscle activity is significantly altered in older patients with
acute infection and that local processes are involved.
PMID- 28502768
TI - Lysosomal enzyme replacement therapies: Historical development, clinical
outcomes, and future perspectives.
AB - Lysosomes and lysosomal enzymes play a central role in numerous cellular
processes, including cellular nutrition, recycling, signaling, defense, and cell
death. Genetic deficiencies of lysosomal components, most commonly enzymes, are
known as "lysosomal storage disorders" or "lysosomal diseases" (LDs) and lead to
lysosomal dysfunction. LDs broadly affect peripheral organs and the central
nervous system (CNS), debilitating patients and frequently causing fatality.
Among other approaches, enzyme replacement therapy (ERT) has advanced to the
clinic and represents a beneficial strategy for 8 out of the 50-60 known LDs.
However, despite its value, current ERT suffers from several shortcomings,
including various side effects, development of "resistance", and suboptimal
delivery throughout the body, particularly to the CNS, lowering the therapeutic
outcome and precluding the use of this strategy for a majority of LDs. This
review offers an overview of the biomedical causes of LDs, their socio-medical
relevance, treatment modalities and caveats, experimental alternatives, and
future treatment perspectives.
PMID- 28502778
TI - The joint association of insulin sensitivity and physical activity on the
skeletal muscle mass and performance in community-dwelling older adults.
AB - BACKGROUND: Many well-known risk factors that may lead to sarcopenia are already
discovered. However, their combined effects on sarcopenia components remain
unclear. This study aims to explore the joint association of physical activity
and insulin sensitivity on skeletal muscle mass and performance of Taiwanese
elder people from a metropolitan community. METHODS: The study sample involved
844 elders who were examined through dual energy X-ray absorptiometry and who
underwent tests for fasting blood glucose and serum insulin level. The
homeostasis model assessment (HOMA-IR) equation estimated insulin sensitivity.
Physical performance was assessed by grip strength and walking speed, while
physical activity status was assessed using the questionnaires answered by the
participants. RESULTS: After multivariate adjustment, the mean height- and weight
adjusted skeletal muscle indexes (SMIs) for old people in the highest tertile of
HOMA-IR values were 6.7kg/m2 and 27.9%, respectively, which were significantly
lower than those of old people in the lowest tertile of HOMA-IR values. Compared
with physically active elders with the lowest tertile of HOMA-IR values, the
physically inactive elders with the highest tertile of HOMA-IR values had
significantly low means in the height-adjusted SMI, weight-adjusted SMI, gait
speed, and grip strength (0.25kg/m2 [p=0.0046], 0.97% [p=0.0068], 0.24m/s
[p<0.0001], and 2.37kg [p=0.0085], respectively). CONCLUSION: Our study
identified the joint associations of physical inactivity and low insulin
sensitivity level on SMI, gait speed, and grip strength. The results provide new
information for sarcopenia screening program that target elders who are
predisposed to have physical dysfunction in old adults living in community.
PMID- 28502779
TI - Microeukaryote community in a partial nitritation reactor prior to anammox and an
insight into the potential of ciliates as performance bioindicators.
AB - An in-depth, long-term, multidisciplinary study was conducted in order to study
the microeukaryote community in a partial nitritation (PN) reactor prior to
anammox. The PN reactor operated with moving bed biofilm reactor (MBBR)
technology, using plastic supports (carriers) for biofilm development. The
microeukaryote community from the biofilm (BF) and the surrounding media (mixed
liquor or ML) were analysed separately. Despite the physicochemical conditions
under which the PN-MBBR operated (an average of 305.9+/-117mg TAN l-1 and 328.4+/
131.9mg N-NO2- l-1), up to 24 microeukaryotic taxa were observed by microscope.
Microeukaryote species showed an uneven distribution in the PN-MBBR, thus
suggesting the existence of two habitats: the BF, preferred by species with
specific structures for adhering to a substrate, such as the stalked Peritrichia,
and the ML, preferred by free-swimming or non-substrate dependent species. The
results indicated that most ciliate population dynamics mainly responded to the
nitrous acid and free ammonia concentrations and, to a lesser extent, to sCOD
values. In the BF, variations in the population of Epistylis camprubii and
Opercularia coarctata suggest the existence of competition between these species
due to niche overlap. A V4 18S rDNA molecular survey (Illumina) was carried out
for some samples with the aim of obtaining maximum coverage of the main eukaryote
species that were microscopically detected throughout the study. The diversity
and abundance data provided by both detection methods were compared. The study
helped identify broader tolerance ranges of the microeukaryote taxa to the
physicochemical parameters analysed.
PMID- 28502780
TI - Biodegradation of endocrine disruptors in urban wastewater using Pleurotus
ostreatus bioreactor.
AB - The white rot fungus Pleurotus ostreatus HK 35, which is also an edible
industrial mushroom commonly cultivated in farms, was tested in the degradation
of typical representatives of endocrine disrupters (EDCs; bisphenol A, estrone,
17beta-estradiol, estriol, 17alpha-ethinylestradiol, triclosan and 4-n
nonylphenol); its degradation efficiency under model laboratory conditions was
greater than 90% within 12 days and better than that of another published strain
P. ostreatus 3004. A spent mushroom substrate from a local farm was tested for
its applicability in various batch and trickle-bed reactors in degrading EDCs in
model fortified and real communal wastewater. The reactors were tested under
various regimes including a pilot-scale trickle-bed reactor, which was finally
tested at a wastewater treatment plant. The result revealed that the spent
substrate is an efficient biodegradation agent, where the fungus was usually able
to remove about 95% of EDCs together with suppression of the estrogenic activity
of the sample. The results showed the fungus was able to operate in the presence
of bacterial microflora in wastewater without any substantial negative effects on
the degradation abilities. Finally, a pilot-scale trickle-bed reactor was
installed in a wastewater treatment plant and successfully operated for 10days,
where the bioreactor was able to remove more than 76% of EDCs present in the
wastewater.
PMID- 28502782
TI - Time-Resolved X-Ray Solution Scattering Reveals the Structural Photoactivation of
a Light-Oxygen-Voltage Photoreceptor.
AB - Light-oxygen-voltage (LOV) receptors are sensory proteins controlling a wide
range of organismal adaptations in multiple kingdoms of life. Because of their
modular nature, LOV domains are also attractive for use as optogenetic actuators.
A flavin chromophore absorbs blue light, forms a bond with a proximal cysteine
residue, and induces changes in the surroundings. There is a gap of knowledge on
how this initial signal is relayed further through the sensor to the effector
module. To characterize these conformational changes, we apply time-resolved X
ray scattering to the homodimeric LOV domain from Bacillus subtilis YtvA. We
observe a global structural change in the LOV dimer synchronous with the
formation of the chromophore photoproduct state. Using molecular modeling, this
change is identified as splaying apart and relative rotation of the two monomers,
which leads to an increased separation at the anchoring site of the effector
modules.
PMID- 28502783
TI - Evolution, expression analysis, and functional verification of Catharanthus
roseus RLK1-like kinase (CrRLK1L) family proteins in pear (Pyrus bretchneideri).
AB - The Catharanthus roseus RLK1-like kinase (CrRLK1L) family is involved in multiple
processes during plant growth. However, little is known about CrRLK1L in the wood
of the pear fruit tree Pyrus bretchneideri. In this study, 26 CrRLK1L gene
members were identified in pear and were grouped into six subfamilies according
to phylogenetic analyses. Evolutionary analysis indicated that recent whole
genome duplication (WGD) and dispersed gene duplications may contribute to the
expansion of the CrRLK1L gene family in pear. Moreover, tissue-specific
expression analyses suggested that CrRLK1Ls are involved in the development of
various pear tissues. Subsequent qRT-PCR analyses indicated that CrRLK1Ls might
play important roles in pollen tube growth. Finally, experiments with antisense
oligonucleotides (ASO) demonstrated that PbrCrRLK1L26 have functions in pollen
tube elongation and that PbrCrRLK1L3 regulates pollen tube rupture. These results
will be useful for elaborating the biological roles of CrRLK1Ls in pear growth
and development.
PMID- 28502784
TI - Liposome loaded phage cocktail: Enhanced therapeutic potential in resolving
Klebsiella pneumoniae mediated burn wound infections.
AB - BACKGROUND: Klebsiella pneumoniae is one of the predominant pathogens in burn
wound infections, and prevalence of multidrug resistant strains has further
complicated the situation. An increased interest in phage therapy as a means of
combating infection has been accruing in recent years. In order to overcome the
drawbacks associated with phage therapy, the present study was conducted to
evaluate the potential of liposomes as a delivery vehicle for phage in the
treatment of burn wound infection. METHODS: Burn wound infection with Klebsiella
pneumoniae B5055 was established in BALB/c mice. The therapeutic efficacy of free
phage cocktail in comparison to liposome entrapped phage cocktail in resolving
the course of burn wound infection in mice was evaluated. RESULTS: The results
depicted that mice treated with liposomal entrapped phage cocktail showed higher
reduction in bacterial load in blood and major organs. This was accompanied with
faster resolution of the entire infection process as compared to non-liposomal
free phage cocktail. The liposomes increased phage retention time in vivo thus
potentiating efficacy. Liposomal phage preparation was able to protect all the
test animals from death even when there was a delay of 24h in instituting the
therapy. CONCLUSION: The results showed the potential of liposome entrapped phage
cocktail for treating Klebsiella pneumoniae mediated infections. Thus, this
strategy can serve as an effective approach for treating Klebsiella mediated burn
wound infections in individuals who do not respond to conventional antibiotic
therapy.
PMID- 28502781
TI - Checks and balances: The glucocorticoid receptor and NFKB in good times and bad.
AB - Mutual regulation and balance between the endocrine and immune systems facilitate
an organism's stress response and are impaired following chronic stress or
prolonged immune activation. Concurrent alterations in stress physiology and
immunity are increasingly recognized as contributing factors to several stress
linked neuropsychiatric disorders including depression, anxiety, and post
traumatic stress disorder. Accumulating evidence suggests that impaired balance
and crosstalk between the glucocorticoid receptor (GR) and nuclear factor kappa
light-chain-enhancer of activated B cells (NFkappaB) - effectors of the stress
and immune axes, respectively - may play a key role in mediating the harmful
effects of chronic stress on mood and behavior. Here, we first review the
molecular mechanisms of GR and NFkappaB interactions in health, then describe
potential shifts in the GR-NFkappaB dynamics in chronic stress conditions within
the context of brain circuitry relevant to neuropsychiatric diseases.
Furthermore, we discuss developmental influences and sex differences in the
regulation of these two transcription factors.
PMID- 28502785
TI - CAR T-cell therapy for lung cancer and malignant pleural mesothelioma.
AB - Immunotherapy is a promising field that harnesses the power of the immune system
as a therapeutic agent for cancer treatment. Beneficial outcomes shown in
patients with non-small cell lung cancer (NSCLC) and malignant pleural
mesothelioma (MPM) with relatively higher tumor-infiltrating T cells, combined
with impressive responses obtained in a cohort of patients with NSCLC following
checkpoint blockade therapy, lays a strong foundation to promote effector immune
responses in these patients. One such approach being investigated is
administration of tumor antigen-targeted T cells with transduction of a chimeric
antigen receptor (CAR). CARs are synthetic receptors that enhance T-cell
antitumor effector function and have gained momentum to investigate in solid
tumors based on recent successes of clinical trials treating patients with B-cell
hematologic malignancies. This review summarizes target antigens for CAR T-cell
therapy that are being investigated in preclinical studies and clinical trials
for both NSCLC and MPM patients. We discuss the rationale for combination
immunotherapies for NSCLC and MPM patients. Additionally, we have highlighted the
challenges and strategies for overcoming the obstacles facing translation of CAR
T-cell therapy to solid tumors.
PMID- 28502786
TI - Randomized Evaluation of Cognitive-Behavioral Therapy and Graded Exercise Therapy
for Post-Cancer Fatigue.
AB - CONTEXT: Cancer-related fatigue is prevalent and disabling. When persistent and
unexplained, it is termed post-cancer fatigue (PCF). Cognitive behavioral therapy
(CBT) and graded exercise therapy (GET) may improve symptoms and functional
outcomes. OBJECTIVES: To evaluate the outcomes of a randomized controlled trial,
which assigned patients with post-cancer fatigue to education, or 12 weeks of
integrated cognitive-behavioral therapy (CBT) and graded exercise therapy (GET).
METHODS: Three months after treatment for breast or colon cancer, eligible
patients had clinically significant fatigue, no comorbid medical or psychiatric
conditions that explained the fatigue, and no evidence of recurrence. The CBT/GET
arm included individually tailored consultations at approximately two weekly
intervals. The education arm included a single visit with clinicians describing
the principles of CBT/GET and a booklet. The primary outcome was clinically
significant improvement in self-reported fatigue (Somatic and Psychological
HEalth REport 0-12), designated a priori as greater than one SD of improvement in
fatigue score. The secondary outcome was associated improvement in function (role
limitation due to physical health problems-36-Item Short Form Health Survey 0
100) comparing baseline, end treatment (12 weeks), and follow-up (24 weeks).
RESULTS: There were 46 patients enrolled, including 43 women (94%), with a mean
age of 51 years. Fatigue severity improved in all subjects from a mean of 5.2 (+/
3.1) at baseline to 3.9 (+/-2.8) at 12 weeks, suggesting a natural history of
improvement. Clinically significant improvement was observed in 7 of 22 subjects
in the intervention group compared with 2 of 24 in the education group (P < 0.05,
chi2). These subjects also had improvement in functional status compared with
nonresponders (P < 0.01, t-test). CONCLUSION: Combined CBT/GET improves fatigue
and functional outcomes for a subset of patients with post-cancer fatigue.
Further studies to improve the response rate and the magnitude of the benefit are
warranted.
PMID- 28502787
TI - No association detected between seven common variants in the CDKAL1 gene and
gestational glycemic traits.
AB - Elevated plasma glucose levels in pregnancy increase adverse pregnancy outcomes.
Cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1)
has been shown to be involved in insulin secretion in pancreatic beta cells. In
this study, we investigated the impact of genetic variants in CDKAL1 on plasma
glucose, insulin values, beta cell function and insulin resistance in the fasted
state as well as plasma glucose 1 h after the consumption of a 50-g oral glucose
load between 24 and 28 weeks of pregnancy among 929 unrelated pregnant Han
Chinese women. Seven common variants previously reported to associate with
diabetes were genotyped. Insulin resistance and beta cell function were assessed
by homeostasis model assessment. The genetic impacts were analyzed using analysis
of variance and analysis of covariance. The results showed that there was no
significant association between any of the seven variants and those gestational
glycemic traits. Therefore, this study suggests that the seven common variants in
CDKAL1 are not significant factors for the variations of several gestational
glycemic traits in the Han Chinese population. However, further well-designed
studies with larger sample size, more ethnic groups and more CDKAL1 variants are
required to validate the association between CDKAL1 and gestational glycemic
traits.
PMID- 28502788
TI - Reply.
PMID- 28502790
TI - Crystallographic and biochemical characterization of the dimeric architecture of
site-2 protease.
AB - Regulated intramembrane proteolysis by members of the site-2 protease family
(S2P) is an essential signal transduction mechanism conserved from bacteria to
humans. There is some evidence that extra-membranous domains, like PDZ and CBS
domains, regulate the proteolytic activity of S2Ps and that some members act as
dimers. Here we report the crystal structure of the regulatory CBS domain pair of
S2P from Archaeoglobus fulgidus, AfS2P, in the apo and nucleotide-bound form in
complex with a specific nanobody from llama. Cross-linking and SEC-MALS analyses
show for the first time the dimeric architecture of AfS2P both in the membrane
and in detergent micelles. The CBS domain pair dimer (CBS module) displays an
unusual head-to-tail configuration and nucleotide binding triggers no major
conformational changes in the magnesium-free state. In solution, MgATP drives
monomerization of the CBS module. We propose a model of the so far unknown
architecture of the transmembrane domain dimer and for a regulatory mechanism of
AfS2P that involves the interaction of positively charged arginine residues
located at the cytoplasmic face of the transmembrane domain with the negatively
charged phosphate groups of ATP moieties bound to the CBS domain pairs. Binding
of MgATP could promote opening of the CBS module to allow lateral access of the
globular cytoplasmic part of the substrate.
PMID- 28502789
TI - Supported lipid bilayer platforms to probe cell mechanobiology.
AB - Mammalian and bacterial cells sense and exert mechanical forces through the
process of mechanotransduction, which interconverts biochemical and physical
signals. This is especially important in contact-dependent signaling, where
ligand-receptor binding occurs at cell-cell or cell-ECM junctions. By virtue of
occurring within these specialized junctions, receptors engaged in contact
dependent signaling undergo oligomerization and coupling with the cytoskeleton as
part of their signaling mechanisms. While our ability to measure and map
biochemical signaling within cell junctions has advanced over the past decades,
physical cues remain difficult to map in space and time. Recently, supported
lipid bilayer (SLB) technologies have emerged as a flexible platform to mimic and
perturb cell-cell and cell-ECM junctions, allowing one to study membrane receptor
mechanotransduction. Changing the lipid composition and underlying substrate
tunes bilayer fluidity, and lipid and ligand micro- and nano-patterning spatially
control positioning and clustering of receptors. Patterning metal gridlines
within SLBs confines lipid mobility and introduces mechanical resistance. Here we
review fundamental SLB mechanics and how SLBs can be engineered as tunable cell
substrates for mechanotransduction studies. Finally, we highlight the impact of
this work in understanding the biophysical mechanisms of cell adhesion. This
article is part of a Special Issue entitled: Interactions between membrane
receptors in cellular membranes edited by Kalina Hristova.
PMID- 28502791
TI - Single-Strand Consensus Sequencing Reveals that HIV Type but not Subtype
Significantly Impacts Viral Mutation Frequencies and Spectra.
AB - A long-standing question of human immunodeficiency virus (HIV) genetic variation
and evolution has been whether differences exist in mutation rate and/or mutation
spectra among HIV types (i.e., HIV-1 versus HIV-2) and among HIV groups (i.e.,
HIV-1 groups M-P and HIV-2 groups A-H) and HIV-1 Group M subtypes (i.e., subtypes
A-D, F-H, and J-K). To address this, we developed a new single-strand consensus
sequencing assay for the determination of HIV mutation frequencies and spectra
using the Illumina sequencing platform. This assay enables parallel and
standardized comparison of HIV mutagenesis among various viral vectors with lower
background error than traditional methods of Illumina library preparation. We
found significant differences in viral mutagenesis between HIV types but
intriguingly no significant differences among HIV-1 Group M subtypes. More
specifically, HIV-1 exhibited higher transition frequencies than HIV-2, due
mostly to single G-to-A mutations and (to a lesser extent) G-to-A hypermutation.
These data suggest that HIV-2 RT exhibits higher fidelity during viral
replication, and taken together, these findings demonstrate that HIV type but not
subtype significantly affects viral mutation frequencies and spectra. These
differences may inform antiviral and vaccine strategies.
PMID- 28502793
TI - Salt-Mediated Oligomerization of the Mouse Prion Protein Monitored by Real-Time
NMR.
AB - The prion protein forms beta-rich soluble oligomers in vitro at pH4 in the
presence of physiological concentrations of salt. In the absence of salt,
oligomerization and misfolding do not take place in an experimentally tractable
timescale. While it is well established that a lowering of pH facilitates
misfolding and oligomerization of this protein, the role of salt remains poorly
understood. Here, solution-state NMR was used to probe perturbations in the
monomeric mouse prion protein structure immediately upon salt addition, prior to
the commencement of the oligomerization reaction. The weak binding of salt at
multiple sites dispersed all over the monomeric protein causes a weak and non
specific perturbation of structure throughout the protein. The only significant
perturbation occurs in the loop between helix 2 and 3 in and around the partially
buried K193-E195 salt bridge. The disruption of this key electrostatic
interaction is the earliest detectable change in the monomer before any major
conformational change occurs and appears to constitute the trigger for the
commencement of misfolding and oligomerization. Subsequently, the kinetics of
monomer loss, due to oligomerization, was monitored at the individual residue
level. The oligomerization reaction was found to be rate-limited by association
and not conformational change, with an average reaction order of 2.6 across
residues. Not surprisingly, salt accelerated the oligomerization kinetics, in a
non-specific manner, by electrostatic screening of the highly charged monomers at
acidic pH. Together, these results allowed a demarcation of the specific and non
specific effects of salt on prion protein misfolding and oligomerization.
PMID- 28502792
TI - Drug Binding Poses Relate Structure with Efficacy in the MU Opioid Receptor.
AB - The MU-opioid receptor (MOPr) is a clinically important G protein-coupled
receptor that couples to Gi/o proteins and arrestins. At present, the receptor
conformational changes that occur following agonist binding and activation are
poorly understood. This study has employed molecular dynamics simulations to
investigate the binding mode and receptor conformational changes induced by
structurally similar opioid ligands of widely differing intrinsic agonist
efficacy, norbuprenorphine, buprenorphine, and diprenorphine. Bioluminescence
resonance energy transfer assays for Gi activation and arrestin-3 recruitment in
human embryonic kidney 293 cells confirmed that norbuprenorphine is a high
efficacy agonist, buprenorphine a low efficacy agonist, and diprenorphine an
antagonist at the MOPr. Molecular dynamics simulations revealed that these
ligands adopt distinct binding poses and engage different subsets of residues,
despite sharing a common morphinan scaffold. Notably, norbuprenorphine interacted
with sodium ion-coordinating residues W2936.48 and N1503.35, whilst buprenorphine
and diprenorphine did not. Principal component analysis of the movements of the
receptor transmembrane domains showed that the buprenorphine-bound receptor
occupied a distinct set of conformations to the norbuprenorphine-bound receptor.
Addition of an allosteric sodium ion caused the receptor and ligand to adopt an
inactive conformation. The differences in ligand-residue interactions and
receptor conformations observed here may underlie the differing efficacies for
cellular signalling outputs for these ligands.
PMID- 28502794
TI - miR-125a-5p Modulates Phenotypic Switch of Vascular Smooth Muscle Cells by
Targeting ETS-1.
AB - MicroRNAs are key regulators of vascular smooth muscle cells (VSMCs) phenotypic
switch, one of the main events responsible for bare metal in-stent restenosis
after percutaneous coronary intervention. miR-125a-5p is an important modulator
of differentiation, proliferation, and migration in different cell types;
however, its role in VSMCs is still unknown. The aim of this study was to
evaluate the role of miR-125a-5p in VSMCs phenotypic switch. Our results suggest
that miR-125a-5p is highly expressed in VSMCs, but it is down-regulated after
vascular injury in vivo. Its overexpression is sufficient to reduce VSMCs
proliferation and migration, and it is able to promote the expression of
selective VSMCs markers such as alpha smooth muscle actin, myosin heavy chain 11,
and smooth muscle 22 alpha. Interestingly, miR-125a-5p directly targets ETS-1, a
transcription factor implicated in cell proliferation and migration and is
crucial in PDGF-BB pathway in VSMCs. Thus, miR-125a-5p in this context inhibits
PDGF-BB pathway and is therefore a potential regulator of VSMCs phenotypic
switch.
PMID- 28502795
TI - Multi-scale, tailor-made heart simulation can predict the effect of cardiac
resynchronization therapy.
AB - BACKGROUND: The currently proposed criteria for identifying patients who would
benefit from cardiac resynchronization therapy (CRT) still need to be optimized.
A multi-scale heart simulation capable of reproducing the electrophysiology and
mechanics of a beating heart may help resolve this problem. The objective of this
retrospective study was to test the capability of patient-specific simulation
models to reproduce the response to CRT by applying the latest multi-scale heart
simulation technology. METHODS AND RESULTS: We created patient-specific heart
models with realistic three-dimensional morphology based on the clinical data
recorded before treatment in nine patients with heart failure and conduction
block treated by biventricular pacing. Each model was tailored to reproduce the
surface electrocardiogram and hemodynamics of each patient in formats similar to
those used in clinical practice, including electrocardiography (ECG),
echocardiography, and hemodynamic measurements. We then performed CRT simulation
on each heart model according to the actual pacing protocol and compared the
results with the clinical data. CRT simulation improved the ECG index and
diminished wall motion dyssynchrony in each patient. These results, however, did
not correlate with the actual response. The best correlation was obtained between
the maximum value of the time derivative of ventricular pressure (dP/dtmax) and
the clinically observed improvement in the ejection fraction (EF) (r=0.94,
p<0.01). CONCLUSIONS: By integrating the complex pathophysiology of the heart,
patient-specific, multi-scale heart simulation could successfully reproduce the
response to CRT. With further verification, this technique could be a useful tool
in clinical decision making.
PMID- 28502797
TI - Understanding the Potential Interethnic Difference in Rosuvastatin
Pharmacokinetics.
AB - Here we address the potential difference in rosuvastatin pharmacokinetics in
Asians vs. whites. Our prospective study, reported in this issue, shows no ethnic
difference when all subjects are wild-type for OATP1B1 and BCRP. We argue that
although our study may be under powered to prove no ethnic difference, and that
further confirmatory study is required, the virtual clinical study analysis, also
reported in this issue, does not contradict the results of our prospective
clinical study and that previous retrospective analysis of clinical studies does
not include enough relevant subjects to conclude that wild-type OATP1B1 and BCRP
do still demonstrate ethnic differences.
PMID- 28502796
TI - In vivo reprogramming for heart regeneration: A glance at efficiency,
environmental impacts, challenges and future directions.
AB - Replacing dying or diseased cells of a tissue with new ones that are converted
from patient's own cells is an attractive strategy in regenerative medicine. In
vivo reprogramming is a novel strategy that can circumvent the hurdles of
autologous/allogeneic cell injection therapies. Interestingly, studies have
demonstrated that direct injection of cardiac transcription factors or specific
miRNAs into the infarct border zone of murine hearts following myocardial
infarction converts resident cardiac fibroblasts into functional cardiomyocytes.
Moreover, in vivo cardiac reprogramming not only drives cardiac tissue
regeneration, but also improves cardiac function and survival rate after
myocardial infarction. Thanks to the influence of cardiac microenvironment and
the same developmental origin, cardiac fibroblasts seem to be more amenable to
reprogramming toward cardiomyocyte fate than other cell sources (e.g. skin
fibroblasts). Thus, reprogramming of cardiac fibroblasts to functional induced
cardiomyocytes in the cardiac environment holds great promises for induced
regeneration and potential clinical purposes. Application of small molecules in
future studies may represent a major advancement in this arena and
pharmacological reprogramming would convey reprogramming technology to the
translational medicine paradigm. This study reviews accomplishments in the field
of in vitro and in vivo mouse cardiac reprogramming and then deals with
strategies for the enhancement of the efficiency and quality of the process.
Furthermore, it discusses challenges ahead and provides suggestions for future
research. Human cardiac reprogramming is also addressed as a foundation for
possible application of in vivo cardiac reprogramming for human heart
regeneration in the future.
PMID- 28502798
TI - Structure of a soluble epoxide hydrolase identified in Trichoderma reesei.
AB - Epoxide hydrolases (EHs) are enzymes that have high biotechnological interest for
the fine and transformation industry. Several of these enzymes have
enantioselectivity, which allows their application in the separation of
enantiomeric mixtures of epoxide substrates. Although two different families of
EHs have been described, those that have the alpha/beta-hidrolase fold are the
most explored for biotechnological purpose. These enzymes are functionally very
well studied, but only few members have three-dimensional structures
characterised. Recently, a new EH from the filamentous fungi Trichoderma reseei
(TrEH) has been discovered and functionally studied. This enzyme does not have
high homology to any other EH structure and have an enatiopreference for (S)-(-)
isomers. Herein we described the crystallographic structure of TrEH at 1.7A
resolution, which reveals features of its tertiary structure and active site.
TrEH has a similar fold to the other soluble epoxide hydrolases and has the two
characteristic hydrolase and cap domains. The enzyme is predominantly monomeric
in solution and has also been crystallised as a monomer in the asymmetric unit.
Although the catalytic residues are conserved, several other residues of the
catalytic groove are not, and might be involved in the specificity for substrates
and in the enantioselectivy of this enzyme. In addition, the determination of the
crystallographic structure of TrEH might contribute to the rational site direct
mutagenesis to generate an even more stable enzyme with higher efficiency to be
used in biotechnological purposes.
PMID- 28502799
TI - Proteomics and metabolomics-driven pathway reconstruction of mung bean for
nutraceutical evaluation.
AB - Mung bean is a legume crop which has a various health-promoting effects. Although
rich flavonoids are reported to be responsible for its biological activities,
little is known about other nutrients that may potentiate the activities. To
obtain information on mung bean nutritional properties, gel-free/label-free
proteomic analysis and metabolomic profiling were combined. Pathway
reconstruction detected that amino acid metabolism is more active in flesh. Coat
contained wider variety of lipids and phenolic acids/flavonoids than flesh. Among
the compounds detected in coat, sphingolipids, arachidonic acid, and
prostaglandin E2 are compounds which are related to immune response induction.
Furthermore, identification of prostaglandin F2alpha added scientific support to
empirical validity of mung bean usage. The abundance of bioactive compounds such
as naringenin, which can be metabolized into vitexin, varied among cultivars.
These results suggest that lipids together with flavonoids might be potential
responsible compounds for biological activity of mung bean coat and flesh.
PMID- 28502800
TI - MicroRNA-211 Regulates Oxidative Phosphorylation and Energy Metabolism in Human
Vitiligo.
AB - Vitiligo is a common chronic skin disorder characterized by loss of epidermal
melanocytes and progressive depigmentation. Vitiligo has complex immune, genetic,
environmental, and biochemical causes, but the exact molecular mechanisms of
vitiligo development and progression, particularly those related to metabolic
control, are poorly understood. In this study we characterized the human vitiligo
cell line PIG3V and the normal human melanocyte line HEM-l by RNA sequencing,
targeted metabolomics, and shotgun lipidomics. Melanocyte-enriched microRNA-211,
a known metabolic switch in nonpigmented melanoma cells, was severely down
regulated in vitiligo cell line PIG3V and skin biopsy samples from vitiligo
patients, whereas its predicted targets PPARGC1A, RRM2, and TAOK1 were
reciprocally up-regulated. microRNA-211 binds to PGC1-alpha 3' untranslated
region locus and represses it. Although mitochondrial numbers were constant,
mitochondrial complexes I, II, and IV and respiratory responses were defective in
vitiligo cells. Nanoparticle-coated microRNA-211 partially augmented the oxygen
consumption rate in PIG3V cells. The lower oxygen consumption rate, changes in
lipid and metabolite profiles, and increased reactive oxygen species production
observed in vitiligo cells appear to be partly due to abnormal regulation of
microRNA-211 and its target genes. These genes represent potential biomarkers and
therapeutic targets in human vitiligo.
PMID- 28502801
TI - Genome-Wide Association Shows that Pigmentation Genes Play a Role in Skin Aging.
AB - Loss of fine skin patterning is a sign of both aging and photoaging. Studies
investigating the genetic contribution to skin patterning offer an opportunity to
better understand a trait that influences both physical appearance and risk of
keratinocyte skin cancer. We undertook a meta-analysis of genome-wide association
studies of a measure of skin pattern (microtopography score) damage in 1,671 twin
pairs and 1,745 singletons (N = 5,087) drawn from three independent cohorts. We
identified that rs185146 near SLC45A2 is associated with a skin aging trait at
genome-wide significance (P = 4.1 * 10-9); to our knowledge this is previously
unreported. We also confirm previously identified loci, rs12203592 near IRF4 (P =
8.8 * 10-13) and rs4268748 near MC1R (P = 1.2 * 10-15). At all three loci we
highlight putative functionally relevant SNPs. There are a number of red hair/low
pigmentation alleles of MC1R; we found that together these MC1R alleles explained
4.1% of variance in skin pattern damage. We also show that skin aging and
reported experience of sunburns was proportional to the degree of penetrance for
red hair of alleles of MC1R. Our work has uncovered genetic contributions to skin
aging and confirmed previous findings, showing that pigmentation is a critical
determinant of skin aging.
PMID- 28502802
TI - Topically Delivered Tumor Necrosis Factor-alpha-Targeted Gene Regulation for
Psoriasis.
PMID- 28502804
TI - WDR79/TCAB1 plays a conserved role in the control of locomotion and ameliorates
phenotypic defects in SMA models.
AB - SMN (Survival Motor Neuron) deficiency is the predominant cause of spinal
muscular atrophy (SMA), a severe neurodegenerative disorder that can lead to
progressive paralysis and death. Although SMN is required in every cell for
proper RNA metabolism, the reason why its loss is especially critical in the
motor system is still unclear. SMA genetic models have been employed to identify
several modifiers that can ameliorate the deficits induced by SMN depletion. Here
we focus on WDR79/TCAB1, a protein important for the biogenesis of several RNA
species that has been shown to physically interact with SMN in human cells. We
show that WDR79 depletion results in locomotion defects in both Drosophila and
Caenorhabditis elegans similar to those elicited by SMN depletion. Consistent
with this observation, we find that SMN overexpression rescues the WDR79 loss-of
function phenotype in flies. Most importantly, we also found that WDR79
overexpression ameliorates the locomotion defects induced by SMN depletion in
both flies and worms. Our results collectively suggest that WDR79 and SMN play
evolutionarily conserved cooperative functions in the nervous system and suggest
that WDR79/TCAB1 may have the potential to modify SMA pathogenesis.
PMID- 28502803
TI - Gene co-expression networks identify Trem2 and Tyrobp as major hubs in human APOE
expressing mice following traumatic brain injury.
AB - Traumatic brain injury (TBI) is strongly linked to an increased risk of
developing dementia, including chronic traumatic encephalopathy and possibly
Alzheimer's disease (AD). APOEepsilon4 allele of human Apolipoprotein E (APOE)
gene is the major genetic risk factor for late onset AD and has been associated
with chronic traumatic encephalopathy and unfavorable outcome following TBI. To
determine if there is an APOE isoform-specific response to TBI we performed
controlled cortical impact on 3-month-old mice expressing human APOE3 or APOE4
isoforms. Following injury, we used several behavior paradigms to test for
anxiety and learning and found that APOE3 and APOE4 targeted replacement mice
demonstrate cognitive impairments following moderate TBI. Transcriptional
profiling 14days following injury revealed a significant effect of TBI, which was
similar in both genotypes. Significantly upregulated by injury in both genotypes
were mRNA expression and protein level of ABCA1 transporter and APOJ, but not
APOE. To identify gene-networks correlated to injury and APOE isoform, we
performed Weighted Gene Co-expression Network Analysis. We determined that the
network mostly correlated to TBI in animals expressing both isoforms is immune
response with major hub genes including Trem2, Tyrobp, Clec7a and Cd68. We also
found a significant increase of TREM2, IBA-1 and GFAP protein levels in the
brains of injured mice. We identified a network representing myelination that
correlated significantly with APOE isoform in both injury groups. This network
was significantly enriched in oligodendrocyte signature genes, such as Mbp and
Plp1. Our results demonstrate unique and distinct gene networks at this acute
time point for injury and APOE isoform, as well as a network driven by APOE
isoform across TBI groups.
PMID- 28502805
TI - Distinct phenotypes of three-repeat and four-repeat human tau in a transgenic
model of tauopathy.
AB - Tau exists as six closely related protein isoforms in the adult human brain.
These are generated from alternative splicing of a single mRNA transcript and
they differ in the absence or presence of two N-terminal and three or four
microtubule binding domains. Typically all six isoforms have been considered
functionally similar. However, their differential involvement in particular
tauopathies raises the possibility that there may be isoform-specific differences
in physiological function and pathological role. To explore this, we have
compared the phenotypes induced by the 0N3R and 0N4R isoforms in Drosophila.
Expression of the 3R isoform causes more profound axonal transport defects and
locomotor impairments, culminating in a shorter lifespan than the 4R isoform. In
contrast, the 4R isoform leads to greater neurodegeneration and impairments in
learning and memory. Furthermore, the phosphorylation patterns of the two
isoforms are distinct, as is their ability to induce oxidative stress. These
differences are not consequent to different expression levels and are suggestive
of bona fide physiological differences in isoform biology and pathological
potential. They may therefore explain isoform-specific mechanisms of tau-toxicity
and the differential susceptibility of brain regions to different tauopathies.
PMID- 28502806
TI - Treadmill exercise delays the onset of non-motor behaviors and striatal pathology
in the CAG140 knock-in mouse model of Huntington's disease.
AB - Depression, cognitive impairments, and other neuropsychiatric disturbances are
common during the prodromal phase of Huntington's disease (HD) well before the
onset of classical motor symptoms of this degenerative disorder. The purpose of
this study was to examine the potential impact of physical activity in the form
of exercise on a motorized treadmill on non-motor behavioral features including
depression-like behavior and cognition in the CAG140 knock-in (KI) mouse model of
HD. The CAG140 KI mouse model has a long lifespan compared to other HD rodent
models with HD motor deficits emerging after 12months of age and thus provides
the opportunity to investigate early life interventions such as exercise on
disease progression. Motorized treadmill running was initiated at 4weeks of age
(1h per session, 3 times per week) and continued for 6months. Non-motor behaviors
were assessed up to 6months of age and included analysis of depression-like
behavior (using the tail-suspension and forced-swim tests) and cognition (using
the T-maze and object recognition tests). At both 4 and 6months of age, CAG140 KI
mice displayed significant depression-like behavior in the forced swim and tail
suspension tests and cognitive impairment by deficits in reversal relearning in
the T-maze test. These deficits were not evident in mice engaged in treadmill
running. In addition, exercise restored striatal dopamine D2 receptor expression
and dopamine neurotransmitter levels both reduced in sedentary HD mice. Finally,
we examined the pattern of striatal expression of mutant huntingtin (mHTT)
protein and showed that the number and intensity of immunohistochemical staining
patterns of intranuclear aggregates were significantly reduced with exercise.
Altogether these findings begin to address the potential impact of lifestyle and
early intervention such as exercise on modifying HD progression.
PMID- 28502807
TI - Augmenting brain metabolism to increase macro- and chaperone-mediated autophagy
for decreasing neuronal proteotoxicity and aging.
AB - Accumulation of toxic protein aggregates in the nerve cells is a hallmark of
neuronal diseases and brain aging. Mechanisms to enhance neuronal surveillance to
improve neuronal proteostasis have a direct impact on promoting neuronal health
and forestalling age-related decline in brain function. Autophagy is a lysosomal
degradative pathway pivotal for neuronal protein quality control. Different types
of autophagic mechanisms participate in protein handling in neurons.
Macroautophagy targets misfolded and aggregated proteins in autophagic vesicles
to the lysosomes for destruction, while chaperone-mediated autophagy (CMA)
degrades specific soluble cytosolic proteins delivered to the lysosomes by
chaperones. Dysfunctions in macroautophagy and CMA contribute to proteo- and
neuro-toxicity associated with neurodegeneration and aging. Thus, augmenting or
preserving both autophagic mechanisms pose significant benefits in delaying
physiological and pathological neuronal demises. Recently, life-style
interventions that modulate metabolite ketone bodies, energy intake by caloric
restriction and energy expenditure by exercise have shown to enhance both
autophagy and brain health. However, to what extent these interventions affect
neuronal autophagy to promote brain fitness remains largely unclear. Here, we
review the functional connections of how macroautophagy and CMA are affected by
ketone bodies, caloric restriction and exercise in the context of
neurodegeneration. A concomitant assessment of yeast Saccharomyces cerevisiae is
performed to reveal the conserved nature of such autophagic responses to
substrate perturbations. In doing so, we provide novel insights and integrated
evidence for a potential adjuvant therapeutic strategy to intervene in the
neuronal decline in neurodegenerative diseases by controlling both macroautophagy
and CMA fluxes favorably.
PMID- 28502808
TI - Series: Pragmatic trials and real world evidence: Paper 3. Patient selection
challenges and consequences.
AB - This paper addresses challenges of identifying, enrolling, and retaining
participants in a trial conducted within a routine care setting. All patients who
are potential candidates for the treatments in routine clinical practice should
be considered eligible for a pragmatic trial. To ensure generalizability, the
recruited sample should have a similar distribution of the treatment effect
modifiers as the target population. In practice, this can be best achieved by
including-within the selected sites-all patients without further selection. If
relevant heterogeneity between subgroups is expected, increasing the relative
proportion of the subgroup of patients in the heterogeneous trial could be
considered (oversampling) or a separate trial in this subgroup can be planned.
Selection will nevertheless occur. Low enrollment and loss to follow-up can
introduce selection and can jeopardize validity as well as generalizability.
Pragmatic trials are conducted in clinical practice rather than in a dedicated
research setting, which could reduce recruitment rates. However, if a trial poses
a minimal burden to the physician and the patient and routine clinical practice
is maximally adhered to, the participation rate may be high and loss to follow-up
will not be a specific problem for pragmatic trials.
PMID- 28502809
TI - Series: Pragmatic trials and real world evidence: Paper 4. Informed consent.
AB - The GetReal consortium of the Innovative Medicines Initiative aims to develop
strategies to incorporate real-world evidence earlier into the drug life cycle to
better inform health care decision makers on the comparative risks and benefits
of new drugs. Pragmatic trials are currently explored as a means to generate such
evidence in routine care settings. The traditional informed consent model for
randomized clinical trials has been argued to pose substantial hurdles to the
practicability of pragmatic trials: it would lead to recruitment difficulties,
reduced generalizability of the results, and selection bias. The present article
analyzes these challenges and discusses four proposed alternative informed
consent models: integrated consent, targeted consent, broadcast consent, and a
waiver of consent. These alternative consent models each aim at overcoming
operational and methodological challenges, while still providing patients all the
relevant information they need to make informed decisions. Each consent model,
however, relies on different attitudes toward the principle of respect for
persons and the related duty to inform patients as well as represents different
views on whether the common good demands moral duties from patients. Such
normative consequences of modifying consent requirements should be at least
acknowledged and ought to be assessed in light of the validity of empirical
claims.
PMID- 28502810
TI - Series: Pragmatic trials and real world evidence: Paper 6. Outcome measures in
the real world.
AB - Results from pragmatic trials should reflect the comparative treatment effects
encountered in patients in real-life clinical practice to guide treatment
decisions. Therefore, pragmatic trials should focus on outcomes that are relevant
to patients, clinical practice, and treatment choices. This sixth article in the
series (see Box) discusses different types of outcomes and their suitability for
pragmatic trials, design choices for measuring these outcomes, and their
implications and challenges. Measuring outcomes in pragmatic trials should not
interfere with real-world clinical practice to ensure generalizability of trial
results, and routinely collected outcomes should be prioritized. Typical outcomes
include mortality, morbidity, functional status, well-being, and resource use.
Surrogate endpoints are typically avoided as primary outcome. It is important to
measure outcomes over a relevant time horizon and obtain valid and precise
results. As pragmatic trials are often open label, a less subjective outcome can
reduce bias. Methods that decrease bias or enhance precision of the results, such
as standardization and blinding of outcome assessment, should be considered when
a high risk of bias or high variability is expected. The selection of outcomes in
pragmatic trials should be relevant for decision making and feasible in terms of
executing the trial in the context of interest. Therefore, this should be
discussed with all stakeholders as early as feasible to ensure the relevance of
study results for decision making in clinical practice and the ability to perform
the study.
PMID- 28502811
TI - Series: Pragmatic trials and real world evidence: Paper 2. Setting, sites, and
investigator selection.
AB - This second article in the series on pragmatic trials describes the challenges in
selection of sites for pragmatic clinical trials and the impact on validity,
precision, and generalizability of the results. The selection of sites is an
important factor for the successful execution of a pragmatic trial and impacts
the extent to which the results are applicable to future patients in clinical
practice. The first step is to define usual care and understand the heterogeneity
of sites, patient demographics, disease prevalence and country choice. Next,
specific site characteristics are important to consider such as interest in the
objectives of the trial, the level of research experience, availability of
resources, and the expected number of eligible patients. It can be advisable to
support the sites with implementing the trial-related activities and minimize the
additional burden that the research imposes on routine clinical practice. Health
care providers should be involved in an early phase of protocol development to
generate engagement and ensure an appropriate selection of sites with patients
who are representative of the future drug users.
PMID- 28502812
TI - Series: Pragmatic trials and real world evidence: Paper 7. Safety, quality and
monitoring.
AB - OBJECTIVE: Pragmatic trials offer the opportunity to obtain real-life data on the
relative effectiveness and safety of a treatment before or after market
authorization. This is the penultimate paper in a series of eight, describing the
impact of design choices on the practical implementation of pragmatic trials.
STUDY DESIGN AND SETTING: This paper focuses on the practical challenges of
collecting and reporting safety data and of monitoring trial conduct while
maintaining routine clinical care practice. CONCLUSION: Current ICH guidance
recommends that all serious adverse events and all drug-related events must be
reported in an interventional trial. In line with current guidance, we propose a
risk-based approach to the collection of non-drug-related non-serious adverse
events and even serious events not related to treatment based on the risk profile
of the medicine/class in the patient population of interest. Different options
available to support the collection and reporting of safety data while minimizing
study-related follow-up visits are discussed. A risk-based approach to monitoring
trial conduct is also discussed, highlighting the difference in the balance of
risks likely to occur in a pragmatic trial compared to traditional clinical
trials and the careful consideration that must be given to the mitigation and
management of these risks to maintain routine care.
PMID- 28502813
TI - The Clinical Relevance of Studies on Borrelia burgdorferi Persisters.
PMID- 28502814
TI - Breathless: Beta Thalassemia Major.
PMID- 28502815
TI - Using Sutton's Law: Yellow Nail Syndrome.
PMID- 28502816
TI - Death and Dignity: Exploring Physicians' Responsibilities After a Patient's
Death.
PMID- 28502817
TI - Concussion.
AB - Concussion has been recognized as a clinical entity for more than 1000 years.
Throughout the 20th century it was studied extensively in boxers, but it did not
pique the interest of the general population because it is the accepted goal of
the boxer to inflict such an injury on their opponent. In 2002, however, the
possibility that repetitive concussions could result in chronic brain damage and
a progressive neurologic disorder was raised by a postmortem evaluation of a
retired player in the most popular sports institution in the United States, the
National Football League. Since that time concussion has been a frequent topic of
conversation in homes, schools, and on television and has become a major focus of
sports programs in communities and schools at all levels. Now all 50 states, the
District of Columbia, and the National Collegiate Athletic Association have
enacted laws and rules to protect the athlete.
PMID- 28502818
TI - Renal Function Considerations for Stroke Prevention in Atrial Fibrillation.
AB - Renal impairment increases risk of stroke and systemic embolic events and
bleeding in patients with atrial fibrillation. Direct oral anticoagulants (DOACs)
have varied dependence on renal elimination, magnifying the importance of
appropriate patient selection, dosing, and periodic kidney function monitoring.
In randomized controlled trials of nonvalvular atrial fibrillation, DOACs were at
least as effective and associated with less bleeding compared with warfarin. Each
direct oral anticoagulant was associated with reduced risk of stroke and systemic
embolic events and major bleeding compared with warfarin in nonvalvular atrial
fibrillation patients with mild or moderate renal impairment. Renal function
decrease appears less impacted by DOACs, which are associated with a better risk
benefit profile than warfarin in patients with decreasing renal function over
time. Limited data address the risk-benefit profile of DOACs in patients with
severe impairment or on dialysis.
PMID- 28502819
TI - Functional relevance of miRNAs in premature ageing.
AB - Ageing is a complex biological process characterized by the progressive loss of
biological fitness due to the accumulation of macromolecular and cellular damage
that affects most living organisms. Moreover, ageing is an important risk factor
for many pathologies, including cardiovascular diseases, neurological disorders,
and cancer. However, the ageing rate can be modulated by genetic, nutritional,
and pharmacological factors, highlighting the concept of "ageing plasticity".
Progeroid syndromes are a group of rare genetic diseases that resemble many
characteristics of physiological ageing. Accordingly, studies on these diseases
have been very useful for gaining mechanistic insights in ageing biology. In
recent years, a great effort has been made in ageing research and several works
have confirmed that geromiRs, the growing subgroup of miRNAs implicated in
ageing, are able to modulate organismal lifespan. However, very little is still
known about the impact of miRNA in premature ageing. In this review, we will
address the functional relevance of this class of small non-coding RNAs in the
regulation of the hallmarks of progeroid syndromes. In addition, we will discuss
the potential strategies for managing progeria based on geromiR modulation.
PMID- 28502820
TI - Cancer-Incidence, prevalence and mortality in the oldest-old. A comprehensive
review.
AB - Chronic health conditions are commonplace in older populations. The process of
aging impacts many of the world's top health concerns. With the average life
expectancy continuing to climb, understanding patterns of morbidity in aging
populations has become progressively more important. Cancer is an age-related
disease, whose risk has been proven to increase with age. Limited information is
published about the epidemiology of cancer and the cancer contribution to
mortality in the 85+ age group, often referred to as the oldest-old. In this
review, we perform a comprehensive assessment of the most recent (2011-2016)
literature on cancer prevalence, incidence and mortality in the oldest-old. The
data shows cancer prevalence and cancer incidence increases until ages 85-89,
after which the rates decrease into 100+ ages. However the number of overall
cases has steadily increased over time due to the rise in population. Cancer
mortality continues to increase after age 85+. This review presents an overview
of plausible associations between comorbidity, genetics and age-related
physiological effects in relation to cancer risk and protection. Many of these
age-related processes contribute to the lowered risk of cancer in the oldest-old,
likewise other certain health conditions may "protect" from cancer in this age
group.
PMID- 28502822
TI - Anti-inflammatory properties of the stem bark from the herbal drug Vitex
peduncularis Wall. ex Schauer and characterization of its polyphenolic profile.
AB - Vitex spp. have been reported as constituents of herbal preparations, namely
Vitex peduncularis, commonly used in Asian countries. Unlike other species
extensively investigated, reports on the biological activities and chemical
profile of V. peduncularis are still scarce. In this work, the polyphenolic
profile of V. peduncularis stem bark was unveiled, revealing a high content of
apigenin and luteolin derivatives. More than 20 polyphenols were identified and
quantitated for the first time, including C-rhamnosyl flavones infrequently
reported. Regarding potential anti-inflammatory properties, the methanolic
extract of the stem bark significantly reduced the levels of NO in macrophages,
which may be a consequence of scavenging effect upon *NO. Significant inhibition
of phospholipase A2 activity was also noted. Consequently, the therapeutic
applicability of this edible plant is also broadened due to the anti-inflammatory
properties found.
PMID- 28502824
TI - Human group 2 innate lymphoid cells do not express the IL-5 receptor.
PMID- 28502821
TI - SASP regulation by noncoding RNA.
AB - Noncoding RNAs (ncRNAs), including micro (mi)RNAs, long noncoding (lnc)RNAs, and
circular (circ)RNAs, control specific gene expression programs by regulating
transcriptional, post-transcriptional, and post-translational processes. Through
their broad influence on protein expression and function, ncRNAs have been
implicated in virtually all cellular processes such as proliferation, senescence,
quiescence, differentiation, apoptosis, and the stress and immune responses.
Senescence is a cellular phenotype associated with the physiologic decline of
aging and with age-related pathologies. Besides their characteristic terminal
growth arrest and differential gene expression programs, senescent cells are
known to secrete potent pro-inflammatory, angiogenic, and tissue-remodeling
factors. This important trait, known as the senescence-associated secretory
phenotype (SASP), influences many biological processes such as tissue repair and
regeneration, tumorigenesis, and the aging-associated pro-inflammatory state.
Here, we review the microRNAs, lncRNAs, and circRNAs that influence the
production of SASP factors and discuss the rising interest in SASP-regulatory
ncRNAs as diagnostic and therapeutic targets.
PMID- 28502825
TI - Treatment of severe forms of LPS-responsive beige-like anchor protein deficiency
with allogeneic hematopoietic stem cell transplantation.
PMID- 28502826
TI - Ovarian Sertoli-Leydig Cell Tumor with Elevated Inhibin B as a Cause of Secondary
Amenorrhea in an Adolescent with Germ Line DICER1 Mutation.
AB - BACKGROUND: Ovarian tumors, although uncommon in children, can retain endocrine
function that disrupts normal feedback mechanisms leading to amenorrhea.
Inheritance of germline DICER1 mutations can lead to increased risk for
development of ovarian Sertoli-Leydig cell tumors (SLCTs). CASE: We report, to
our knowledge, the first case of secondary amenorrhea due to elevated inhibin B
levels in a female adolescent with an ovarian SLCT. SUMMARY AND CONCLUSION:
Ovarian tumors should be included in the differential diagnosis for pediatric
patients who present with menstrual irregularities. Early evaluation of the
hypothalamic-pituitary-ovarian axis and inhibin levels is appropriate. Our case
also emphasizes the need for testing for DICER1 mutations in pediatric patients
with ovarian SLCTs.
PMID- 28502823
TI - NIAID, NIEHS, NHLBI, and MCAN Workshop Report: The indoor environment and
childhood asthma-implications for home environmental intervention in asthma
prevention and management.
AB - Environmental exposures have been recognized as critical in the initiation and
exacerbation of asthma, one of the most common chronic childhood diseases. The
National Institute of Allergy and Infectious Diseases; National Institute of
Environmental Health Sciences; National Heart, Lung, and Blood Institute; and
Merck Childhood Asthma Network sponsored a joint workshop to discuss the current
state of science with respect to the indoor environment and its effects on the
development and morbidity of childhood asthma. The workshop included US and
international experts with backgrounds in allergy/allergens, immunology, asthma,
environmental health, environmental exposures and pollutants, epidemiology,
public health, and bioinformatics. Workshop participants provided new insights
into the biologic properties of indoor exposures, indoor exposure assessment, and
exposure reduction techniques. This informed a primary focus of the workshop: to
critically review trials and research relevant to the prevention or control of
asthma through environmental intervention. The participants identified important
limitations and gaps in scientific methodologies and knowledge and proposed and
prioritized areas for future research. The group reviewed socioeconomic and
structural challenges to changing environmental exposure and offered
recommendations for creative study design to overcome these challenges in trials
to improve asthma management. The recommendations of this workshop can serve as
guidance for future research in the study of the indoor environment and on
environmental interventions as they pertain to the prevention and management of
asthma and airway allergies.
PMID- 28502828
TI - Premature Ovarian Insufficiency: An Adolescent Series.
AB - STUDY OBJECTIVE: To study the presentation and causes of premature ovarian
insufficiency (POI) in adolescents. DESIGN: Retrospective notes review. SETTING:
Tertiary referral outpatient clinic for pediatric and adolescent gynecology.
PARTICIPANTS: Adolescents with POI. INTERVENTIONS: Standard POI evaluation. MAIN
OUTCOME MEASURES: Age and clinical symptoms at presentation, causative factors
for POI, if identified. RESULTS: We identified 22 girls with POI, with a mean age
of 15.6 years. Eight of them presented with delayed puberty, 3 with primary
amenorrhea, and the remainder presented with either irregular bleeding (n = 9) or
secondary amenorrhea (n = 2). For those who presented with delayed puberty, only
3 were found to have a sex chromosome abnormality. A clear cause for the POI was
identified in 3 further cases. CONCLUSION: Although POI in adolescents
traditionally is associated with primary amenorrhea and delayed puberty, a
proportion of girls will present with irregular bleeding that might be mistaken
for expected menstrual disturbances of puberty, thus delaying the diagnosis. We
identified a clear cause for POI in 6 cases. Although there were no familial
cases of POI, it remains a possibility that genetic reasons might be involved in
the pathogenesis.
PMID- 28502827
TI - Provider and Health System Factors Associated with Usage of Long-Acting
Reversible Contraception in Adolescents.
AB - STUDY OBJECTIVE: Long-acting reversible contraception (LARC) is recommended as
first-line contraception for adolescents. Surveys of primary care providers
suggest that physician and clinic factors might influence LARC counseling, but
their effect on usage is unknown. Our objective was to explore provider and
clinic characteristics associated with LARC usage in adolescents. DESIGN,
SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: We conducted a
cross-sectional study of 5363 women ages 15-21 years receiving primary care
within a large health system in Massachusetts in 2015. We used data abstracted
from electronic medical records to characterize rates of LARC usage. We analyzed
the association of provider (specialty, degree, gender, resident status, LARC
credentialing) and clinic (Title X funding, onsite LARC provision, onsite
obstetrician-gynecologist) factors with adolescents' LARC usage using
multivariate logistic regression. RESULTS: Overall, 3.4% (95% confidence interval
[CI], 2.9-3.9) of adolescents were documented as currently using a LARC method.
Older adolescents were significantly more likely to use a LARC method (adjusted
odds ratio, 2.41; 95% CI, 1.62-3.58 for women ages 20-21 years compared with ages
15-17 years). Adolescents whose primary care provider was a resident were
significantly more likely to use a LARC method (adjusted odds ratio, 1.65; 95%
CI, 1.02-2.68). Provider specialty, degree, gender, onsite LARC provision, and
onsite obstetrician-gynecologist were not significantly associated with LARC
usage in adolescents. CONCLUSION: Being older and having a primary care provider
early in their training increased the odds of LARC usage among adolescents in a
large Massachusetts health system. Across primary care specialties, educating
providers about the appropriate uses of LARC methods in nulliparous adolescents
might facilitate LARC usage.
PMID- 28502829
TI - Primary Ovarian Fibrosarcoma-An Unusual Tumor in an Adolescent: Case Report and
Review of the Pediatric Literature.
AB - BACKGROUND: Primary ovarian fibrosarcomas are rare and usually observed in
perimenopausal and postmenopausal women. To our knowledge, to date, there are
only 3 reports of ovarian fibrosarcoma in childhood and adolescence in the
English-language literature. In this report, we aimed to present to our
knowledge, the first pediatric case with advanced stage primary ovarian
fibrosarcoma and to compare with previous cases. CASE: A 14-year-old teenage girl
was admitted because of a giant abdominal mass. Imaging techniques revealed a
giant heterogeneous and vascular ovarian mass. Salpingo-oophorectomy along with
staging procedures were performed. Pathologic examination confirmed grade III
ovarian fibrosarcoma with severe nuclear atypia and high mitotic count. Because
of pulmonary metastasis, she received 4 courses of adjuvant combination
chemotherapy (Ewing protocol). The patient withstood the treatment well and is
disease-free at 2 years of follow-up. CONCLUSION: Fibrosarcoma of the ovary is an
uncommon neoplasm with poor prognosis. To our knowledge, the presented patient is
the first pediatric case with advanced staged primary ovarian fibrosarcoma to be
treated with surgery and adjuvant chemotherapy.
PMID- 28502830
TI - With me or against me: Tumor suppressor and drug resistance activities of SAMHD1.
AB - Sterile alpha motif and histidine/aspartic acid domain-containing protein 1
(SAMHD1) is a (deoxy)guanosine triphosphate (dGTP/GTP)-activated
deoxyribonucleoside triphosphate (dNTP) triphosphohydrolase involved in cellular
dNTP homoeostasis. Mutations in SAMHD1 have been associated with the
hyperinflammatory disease Aicardi-Goutieres syndrome (AGS). SAMHD1 also limits
cells' permissiveness to infection with diverse viruses, including human
immunodeficiency virus (HIV-1), and controls endogenous retroviruses. Increasing
evidence supports the role of SAMHD1 as a tumor suppressor. However, SAMHD1 also
can act as a resistance factor to nucleoside-based chemotherapies by hydrolyzing
their active triphosphate metabolites, thereby reducing response of various
malignancies to these anticancer drugs. Hence, informed cancer therapies must
take into account the ambiguous properties of SAMHD1 as both an inhibitor of
uncontrolled proliferation and a resistance factor limiting the efficacy of
anticancer treatments. Here, we provide evidence that SAMHD1 is a double-edged
sword for patients with acute myelogenous leukemia (AML). Our time-dependent
analyses of The Cancer Genome Atlas (TCGA) AML cohort indicate that high
expression of SAMHD1, even though it critically limits the efficacy of high-dose
ara-C therapy, might be associated with more favorable disease progression.
PMID- 28502831
TI - A 12-week randomized clinical trial investigating the potential for sucralose to
affect glucose homeostasis.
AB - The discovery of gut sweet taste receptors has led to speculations that non
nutritive sweeteners, including sucralose, may affect glucose control. A double
blind, parallel, randomized clinical trial, reported here and previously
submitted to regulatory agencies, helps to clarify the role of sucralose in this
regard. This was primarily an out-patient study, with 4-week screening, 12-week
test, and 4-week follow-up phases. Normoglycemic male volunteers (47) consumed
~333.3 mg encapsulated sucralose or placebo 3x/day at mealtimes. HbA1c, fasting
glucose, insulin, and C-peptide were measured weekly. OGTTs were conducted in
clinic overnight, following overnight fasting twice during screening phase, twice
during test phase, and once at follow-up. Throughout the study, glucose, insulin,
C-peptide and HbA1c levels were within normal range. No statistically significant
differences between sucralose and placebo groups in change from baseline for
fasting glucose, insulin, C-peptide and HbA1c, no clinically meaningful
differences in time to peak levels or return towards basal levels in OGTTs, and
no treatment group differences in mean glucose, insulin, or C-peptide AUC change
from baseline were observed. The results of other relevant clinical trials and
studies of gastrointestinal sweet taste receptors are compared to these findings.
The collective evidence supports that sucralose has no effect on glycemic
control.
PMID- 28502833
TI - Overactive Bladder Is Strongly Associated With Frailty in Older Individuals.
AB - OBJECTIVE: To understand the relationship between age, frailty, and overactive
bladder (OAB). MATERIALS AND METHODS: This is a prospective study of individuals
age >=65 years presenting to an academic urology practice between December 2015
and July 2016. All patients had a Timed Up and Go Test (TUGT), a parsimonious
measure of frailty, on intake, and were thereby categorized as fast (<=10
seconds), intermediate (11-14 seconds), and slow (>=15 seconds). The TUGT and
other clinical data were abstracted from the electronic medical record using
direct queries. Logistic regression was used to examine the relationship between
frailty and the diagnosis of OAB, adjusting for age, gender, and race. RESULTS:
Our cohort included 201 individuals with and 1162 individuals without OAB.
Individuals with OAB had slower TUGTs (13.7 +/- 7.9 seconds) than their non-OAB
counterparts (10.9 +/- 5.2 seconds), P <.0001, with 32.3% and 11.0% of OAB and
non-OAB individuals being categorized as slow, or frail. In multivariable
analysis, slower TUGT was a significant predictor of OAB (adjusted odds ratio:
3.0; 95% confidence interval: 2.0-4.8). Age was not independently associated with
this diagnosis (P values >.05 for each age group). CONCLUSION: Patients with OAB
are statistically significantly frailer than individuals seeking care for other
non-oncologic urologic diagnoses. Frailty, when adjusted for age, race, and
gender, is a statistically significant predictor of OAB. Furthermore, frailty
should be considered when caring for older patients with OAB, and OAB should be
assessed when caring for frail older patients.
PMID- 28502834
TI - A Rare Case of Intravesical Angiomyofibroblastoma.
AB - OBJECTIVE: To study the first reported case of intravesical angiomyofibroblastoma
(AMFB). AMFB is an uncommon benign mesenchymal lesion, mostly described in the
lower female genital tract, especially in the vulva and less commonly in the
vagina. It is rarely seen in the male genital tract. The importance of this rare
neoplasm is related to its potential mimicry of more infiltrative and
prognostically less favorable lesions, such as aggressive angiomyxomas, that are
found in the same anatomic area. METHODS: A 26-year-old man presented to us with
hematuria. Investigations revealed an intraluminal polypoidal lesion of
approximately 92 * 77 * 76 mm within the urinary bladder. Cystoscopy revealed a
large well-circumscribed tumor with a pedicle, attached to the inferolateral wall
of the bladder near the bladder neck. Open exploration and en bloc excision of
the bladder mass was done. RESULTS: Histopathology and immunohistochemistry (IHC)
confirmed the diagnosis of AMFB. CONCLUSION: AMFB presents as a well
circumscribed superficial mass. Complete excision of the tumor for
histopathologic and IHC examination is essential for diagnosis. This rare tumor
shows morphologic similarity to some more aggressive tumors with less favorable
outcome; hence, it needs to be differentiated from those. IHC is helpful but not
always conclusive in the diagnosis of this rare neoplasm. This being the first
ever reported case of intravesical AMFB bears a significant importance. Careful
clinical assessment, operative management, and histopathologic examination are of
utmost importance in making a precise diagnosis and management of the patient.
PMID- 28502832
TI - Sexually dimorphic expression in developing and adult gonads shows an important
role of gonadal soma-derived factor during sex differentiation in olive flounder
(Paralichthys olivaceus).
AB - Gonadal soma-derived factor (gsdf) is a new member of transforming growth factor
beta (TGF-beta) superfamily. As a teleost- and gonad-specific growth factor, gsdf
has been indicated to play an important role in early germ cell development.
However, little is known about its significance in germ cell development of olive
flounder (Paralichthys olivaceus). In the present study, a 1338 bp gsdf gene was
isolated from P. olivaceus for the first time. Bioinformatic analysis revealed
that the genomic structure and synteny relationship of gsdf in teleosts were
conserved. Quantitative real-time PCR (qRT-PCR) showed that gsdf expressed before
sex gonadal differentiation, and the expression level increased rapidly after
initiation of sex differentiation in males. In adult individuals, the expression
of gsdf was higher in testis than that in ovary (P<0.01). In situ hybridization
(ISH) indicated that gsdf mRNA was detected in the somatic cells of both males
and females, and also in the cytoplasm of oocytes. These results suggested that
gsdf might play an important role as initial switches to promote testis
differentiation and participate in early germ cell development, such as
proliferation and differentiation of spermatogonia and oogonia in P. olivaceus.
PMID- 28502836
TI - Selection of differently temporally regulated African swine fever virus promoters
with variable expression activities and their application for transient and
recombinant virus mediated gene expression.
AB - African swine fever virus threatens pig production worldwide due to the lack of
vaccines, for which generation of both deletion and insertion mutants is
considered. For development of the latter, operational ASFV promoters of
different temporal regulation and strengths are desirable. We therefore compared
the capacities of putative promoter sequences from p72, CD2v, p30, viral DNA
polymerase and U104L genes to mediate expression of luciferase from transfected
plasmids after activation in trans, or p30-, DNA polymerase- and U104L promoters
in cis, using respective ASFV recombinants. We identified sequences with promoter
activities upstream the viral ORFs, and showed that they differ in both their
expression intensity regulating properties and in their temporal regulation. In
summary, p30 and DNA polymerase promoters are recommended for high level early
regulated transgene expression. For late expression, the p72, CD2v and U104L
promoter are suitable. The latter however, only if low level transgene expression
is aimed.
PMID- 28502835
TI - The ADMA/DDAH/NO pathway in human vein endothelial cells exposed to arsenite.
AB - Inorganic arsenic (iAs) exposure is related to cardiovascular disease, which is
characterized by endothelial dysfunction and nitric oxide (NO) depletion. The
mechanisms underlying NO depletion as related to iAs exposure are not fully
understood. The endogenous inhibitor of nitric oxide synthase, asymmetric
dimethylarginine (ADMA), might be a molecular target of iAs. ADMA concentrations
are regulated by proteins involved in its synthesis (arginine methyl transferase
1 [PRMT-1]) and degradation (dimethylarginine dimethylaminohydrolase [DDAH]).
Both, ADMA and NO are susceptible to oxidative stress. We aimed to determine the
ADMA/DDAH/NO pathway in human vein endothelial cells (HUVEC-CS) exposed to
arsenite. We exposed HUVEC-CS cells to 1, 2.5 and 5MUM of arsenite for 24h. We
proved that arsenite at 5MUM was able to decrease NO levels with an associated
increase in ADMA and depletion of l-arginine in HUVEC-CS cells. We also found a
decrease in DDAH-1 protein expression with 5MUM of arsenite compared to the
control group. However, we did not observe significant differences in PRMT-1
protein expression at any of the concentrations of arsenite employed. Finally,
arsenite (2.5 and 5MUM) increased NADPH oxidase 4 protein levels compared with
the control group. We conclude that ADMA, l-arginine and DDAH are involved in NO
depletion produced by arsenite, and that the mechanism is related to oxidative
stress.
PMID- 28502837
TI - Use of technology to facilitate physical activity in children with autism
spectrum disorders: A pilot study.
AB - Deficits in social behavior and communication skills are correlated with reduced
gross motor skills in children with autism spectrum disorders (ASD). The
ExerciseBuddy application (EB app) was designed to communicate these motor skills
to those with ASD and integrates evidence-based practices such as visual support
and video modeling supported by The National Professional Development Center on
Autism Spectrum Disorders. The purpose of this study was to determine the
effectiveness of the EB app in facilitating increased physiologic responses to
physical activity via a continuous measurement of energy expenditure and heart
rate versus practice-style teaching methods in children with ASD. Six children,
ages 5 to 10years, diagnosed with ASD were recruited. Each participant performed
a variety of locomotor or object control skills as defined by the Test of Gross
Motor Development-2 once per week for 4weeks. Motor skills were communicated and
demonstrated using either practice-style teaching methods or the instructional
section of the EB app. Energy expenditure and heart rate were measured
continuously during each 12-minute session. A Wilcoxon signed-rank test was
performed to assess any differences between the use of the app and practice-style
teaching methods. The use of the EB app elicited greater values for peak energy
expenditure (p=0.043) and peak heart rate response (p=0.028) while performing
locomotor skills but no differences were observed while performing object control
skills. Similarities were observed with average physiologic responses between the
use of the EB app and practice-style teaching methods. The use of the EB app may
allow for a greater peak physiologic response during more dynamic movements and a
similar average cardiovascular and metabolic response when compared to practice
style teaching methods in children with ASD.
PMID- 28502838
TI - Sleep quality and duration are associated with performance in maximal incremental
test.
AB - BACKGROUND AND OBJECTIVE: Inadequate sleep patterns may be considered a trigger
to development of several metabolic diseases. Additionally, sleep deprivation and
poor sleep quality can negatively impact performance in exercise training.
However, the impact of sleep duration and sleep quality on performance during
incremental maximal test performed by healthy men is unclear. Therefore, the
purpose of the study was to analyze the association between sleep pattern
(duration and quality) and performance during maximal incremental test in healthy
male individuals. METHODS: A total of 28 healthy males volunteered to take part
in the study. Sleep quality, sleep duration and physical activity were
subjectively assessed by questionnaires. Sleep pattern was classified by sleep
duration (>7h or <7h of sleep per night) and sleep quality according to the sum
of measured points and/or scores by the Pittsburgh Sleep Quality Index (PSQI).
Incremental exercise test was performed at 35 watts for untrained subjects, 70
watts for physically active subjects and 105 watts for well-trained subjects.
RESULTS: HRmax was correlated with sleep quality (r=0.411, p=0.030) and sleep
duration (r=-0.430, p=0.022). Participants reporting good sleep quality presented
higher values of Wmax, VO2max and lower values of HRmax when compared to
participants with altered sleep. Regarding sleep duration, only Wmax was
influenced by the amount of sleeping hours per night and this association
remained significant even after adjustment by VO2max. CONCLUSION: Sleep duration
and quality are associated, at least in part, with performance during maximal
incremental test among healthy men, with losses in Wmax and HRmax. In addition,
our results suggest that the relationship between sleep patterns and performance,
mainly in Wmax, is independent of fitness condition.
PMID- 28502839
TI - Predictors of failure after single faecal microbiota transplantation in patients
with recurrent Clostridium difficile infection: results from a 3-year cohort
study: authors' reply.
PMID- 28502840
TI - The Perfect Transplant.
PMID- 28502841
TI - Use of airway epithelial cell culture to unravel the pathogenesis and study
treatment in obstructive airway diseases.
AB - Asthma and chronic obstructive pulmonary disease (COPD) are considered as two
distinct obstructive diseases. Both chronic diseases share a component of airway
epithelial dysfunction. The airway epithelium is localized to deal with inhaled
substances, and functions as a barrier preventing penetration of such substances
into the body. In addition, the epithelium is involved in the regulation of both
innate and adaptive immune responses following inhalation of particles, allergens
and pathogens. Through triggering and inducing immune responses, airway
epithelial cells contribute to the pathogenesis of both asthma and COPD. Various
in vitro research models have been described to study airway epithelial cell
dysfunction in asthma and COPD. However, various considerations and cautions have
to be taken into account when designing such in vitro experiments. Epithelial
features of asthma and COPD can be modelled by using a variety of disease-related
invoking substances either alone or in combination, and by the use of primary
cells isolated from patients. Differentiation is a hallmark of airway epithelial
cells, and therefore models should include the ability of cells to differentiate,
as can be achieved in air-liquid interface models. More recently developed in
vitro models, including precision cut lung slices, lung-on-a-chip, organoids and
human induced pluripotent stem cells derived cultures, provide novel state-of-the
art alternatives to the conventional in vitro models. Furthermore, advanced
models in which cells are exposed to respiratory pathogens, aerosolized
medications and inhaled toxic substances such as cigarette smoke and air
pollution are increasingly used to model e.g. acute exacerbations. These exposure
models are relevant to study how epithelial features of asthma and COPD are
affected and provide a useful tool to study the effect of drugs used in treatment
of asthma and COPD. These new developments are expected to contribute to a better
understanding of the complex gene-environment interactions that contribute to
development and progression of asthma and COPD.
PMID- 28502842
TI - Attentional capture in visual search: Capture and post-capture dynamics revealed
by EEG.
AB - Sometimes, salient-but-irrelevant objects (distractors) presented concurrently
with a search target cannot be ignored and attention is involuntarily allocated
towards the distractor first. Several studies have provided electrophysiological
evidence for involuntary misallocations of attention towards a distractor, but
much less is known about the mechanisms that are needed to overcome a
misallocation and re-allocate attention towards the concurrently presented
target. In our study, electrophysiological markers of attentional mechanisms
indicate that (i) the distractor captures attention before the target is
attended, (ii) a misallocation of attention is terminated actively (instead of
attention fading passively), and (iii) the misallocation of attention towards a
distractor delays the attention allocation towards the target (rather than just
delaying some post-attentive process involved in response selection). This
provides the most complete demonstration, to date, of the chain of attentional
mechanisms that are evoked when attention is misguided and recovers from capture
within a search display.
PMID- 28502843
TI - Disentangling the effects of novelty, valence and trait anxiety in the bed
nucleus of the stria terminalis, amygdala and hippocampus with high resolution 7T
fMRI.
AB - The hippocampus and amygdala exhibit sensitivity to stimulus novelty that is
reduced in participants with inhibited temperament, which is related to trait
anxiety. Although the bed nucleus of the stria terminalis (BNST) is highly
connected to the amygdala and is implicated in anxiety, whether the BNST responds
to novelty remains unstudied, as well as how trait anxiety may modulate this
response. Additionally how novelty, stimulus negativity and trait anxiety
interact to affect activity in these areas is also unclear. To address these
questions, we presented participants with novel and repeated, fearful and neutral
faces, while measuring brain activity via fMRI, and also assessed participants'
self-reported trait anxiety. As the small size of the BNST makes assessing its
activity at typical fMRI resolution difficult, we employed high resolution 7
Tesla scanning. Our results replicate findings of novelty sensitivity that is
independent of valence in the hippocampus. Our results also provide novel
evidence for a BNST novelty response toward neutral, but not fearful faces. We
also found that the novelty response in the hippocampus and BNST was blunted in
participants with high trait anxiety. Additionally, we found left amygdala
sensitivity to stimulus negativity that was blunted for high trait anxiety
participants. These findings extend past research on the response to novel
stimuli in the hippocampus and amygdala at high resolution, and are the first to
demonstrate trait anxiety modulated novelty sensitivity in the BNST that is
dependent on stimulus valence.
PMID- 28502844
TI - A novel approach to map induced activation of neuronal networks using
chemogenetics and functional neuroimaging in rats: A proof-of-concept study on
the mesocorticolimbic system.
AB - Linking neural circuit activation at whole-brain level to neuronal activity at
cellular level remains one of the major challenges in neuroscience research. We
set up a novel functional neuroimaging approach to map global effects of locally
induced activation of specific midbrain projection neurons using chemogenetics
(Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-technology)
combined with pharmacological magnetic resonance imaging (phMRI) in the rat
mesocorticolimbic system. Chemogenetic activation of DREADD-targeted mesolimbic
or mesocortical pathways, i.e. projections from the ventral tegmental area (VTA)
to the nucleus accumbens (NAcc) or medial prefrontal cortex (mPFC), respectively,
induced significant blood oxygenation level-dependent (BOLD) responses in areas
with DREADD expression, but also in remote defined neural circuitry without
DREADD expression. The time-course of brain activation corresponded with the
behavioral output measure, i.e. locomotor (hyper)activity, in the mesolimbic
pathway-targeted group. Chemogenetic activation specifically increased neuronal
activity, whereas functional connectivity assessed with resting state functional
MRI (rs-fMRI) remained stable. Positive and negative BOLD responses distinctively
reflected simultaneous ventral pallidum activation and substantia nigra pars
reticulata deactivation, respectively, demonstrating the concept of
mesocorticolimbic network activity with concurrent activation of the direct and
indirect pathways following stimulation of specific midbrain projection neurons.
The presented methodology provides straightforward and widely applicable
opportunities to elucidate relationships between local neuronal activity and
global network activity in a controllable manner, which will increase our
understanding of the functioning and dysfunctioning of large-scale neuronal
networks in health and disease.
PMID- 28502846
TI - Domains of physical activity and brain volumes: A population-based study.
AB - Observational studies and intervention trials suggest that physical activity (PA)
is beneficial for human brain morphology, especially in older individuals. Few
population-based studies examined whether domain-specific PA is associated with
brain volumes. Accordingly, we studied putative associations of PA during leisure
time, sports and work with volumes of the hippocampus, the prefrontal cortex, the
temporal lobe, gray matter (GM), white matter (WM) and total brain (TBV) after
5.9 years by applying volumetric analysis and voxel-based morphometry (VBM) with
SPM 8/VBM 8 to brain magnetic resonance imaging data of 834 participants (447
women) aged 25 to 83 years from the population-based Study of Health in
Pomerania. The Baecke questionnaire was used to assess domain-specific PA
(Leisure time, Sport, and Work Index) at baseline. After correcting for multiple
testing, volumetric analyses did not show any significant association of domain
specific PA and volumes of the hippocampus, the prefrontal cortex, the temporal
lobe, GM, WM and TBV. Multivariable-adjusted VBM analyses of the associations
between PA domains with GM and WM volumes did not reveal any statistically
significant results. Region of interest analyses revealed a statistically
significant cluster of increased GM volume in the bilateral anterior cingulate
cortex in association with PA during sports. In conclusion, the overall results
contrast with the findings from previous studies that found significant
associations between PA and brain volumes. In addition, it remains unclear
whether a differential association exists between domains of PA and brain
volumes. Thus, future studies with larger sample size and prospective design are
needed to investigate potential domain-specific associations of PA with brain
volumes.
PMID- 28502848
TI - Exercise Training In Athletes With Heart Disease.
AB - Exercise events and sport participation have increased over recent decades. The
average age of sports participants has also increased with a potential parallel
increase in the number of exercise participants with both occult and diagnosed
cardiovascular disease (CVD). Habitual physical activity and exercise training
reduce atherosclerotic CVD (ASCVD) risk in a curvilinear fashion by affecting
multiple ASCVD risk factors. Nonetheless, exercise also increases the risk of
sudden cardiac death in both young and adult individuals with occult CVD making
it important to balance the risks and benefits of exercise and exercise training
in these individuals. There are essentially no carefully designed clinical trials
to inform clinicians how to definitely manage athletes with occult CVD. We
provide a narrative review of the risks and benefits of exercise in active
individuals with CVD, and our approach to evaluating and managing these risks.
PMID- 28502847
TI - The Role for Cardiologists in Stroke Intervention.
AB - Even though cardiovascular disease (CVD) is still the leading cause of death in
the United States, stroke is the second leading global cause of death behind CVD.
In the 21st Century, less than 40% of overall stroke patients are discharged to
home and almost 25% of Medicare beneficiaries do not survive 90 days. In spite of
the fact that tissue plasminogen activator (TPA) has been approved for stroke
care for 20 years, only .75% of annual strokes are actually treated with
intravenous (IV) TPA. Similar to how interventional cardiologists evolved from IV
to catheter mechanical treatment for acute myocardial infarctions (AMI) over 30
years ago, over the last few years, neurointerventionists now perform
endovascular stroke therapy in many of these patients using stent retrievers.
However, very few stroke patients are actually getting treatment, and
neurointerventionists on an average perform only 8 stroke interventions per year.
It has been recently shown that 9 out of 10 strokes can be prevented by
controlling CVD risk factors. A principal job for cardiologists is to recognize
and manage these CVD risk factors in addition to being involved with performing
intervention. Atrial Fibrillation is certainly a common problem in all of our
practices and puts people at five-fold higher risk of stroke. Cardiovascular
cardiology teams already have 24/7 coverage for acute interventions for AMI in
place at their facilities. A number of groups have replicated acute stroke care
performed by cardiologists at centers worldwide with outstanding results. It
makes sense that we try to build a collaboration among neuroradiologists,
interventional cardiologists and perhaps vascular or neurosurgeons with expertise
in acute endovascular procedures to develop programs for acute and active 24/7
stroke care similar to systems for primary angioplasty for AMI.
PMID- 28502845
TI - Foundations of layer-specific fMRI and investigations of neurophysiological
activity in the laminarized neocortex and olfactory bulb of animal models.
AB - Laminar organization of neuronal circuits is a recurring feature of how the brain
processes information. For instance, different layers compartmentalize different
cell types, synaptic activities, and have unique intrinsic and extrinsic
connections that serve as units for specialized signal processing. Functional MRI
is an invaluable tool to investigate laminar processing in the in vivo human
brain, but it measures neuronal activity indirectly by way of the hemodynamic
response. Therefore, the accuracy of high-resolution laminar fMRI depends on how
precisely it can measure localized microvascular changes nearest to the site of
evoked activity. To determine the specificity of fMRI responses to the true
neurophysiological responses across layers, the flexibility to invasive
procedures in animal models has been necessary. In this review, we will examine
different fMRI contrasts and their appropriate uses for layer-specific fMRI, and
how localized laminar processing was examined in the neocortex and olfactory
bulb. Through collective efforts, it was determined that microvessels, including
capillaries, are regulated within single layers and that several endogenous and
contrast-enhanced fMRI contrast mechanisms can separate these neural-specific
vascular changes from the nonspecific, especially cerebral blood volume-weighted
fMRI with intravenous contrast agent injection. We will also propose some open
questions that are relevant for the successful implementation of layer-specific
fMRI and its potential future directions to study laminar processing when
combined with optogenetics.
PMID- 28502849
TI - The Interaction of Cardiorespiratory Fitness With Obesity and the Obesity Paradox
in Cardiovascular Disease.
AB - Overweight and obesity are well-established risk factors for most cardiovascular
diseases (CVD), including coronary heart disease (CHD), heart failure (HF), and
atrial fibrillation. Despite the strong link between excess adiposity and risk of
CVD, growing evidence has demonstrated an obesity paradox in patients with CVD.
This phenomenon is characterized by a better prognosis in overweight and mildly
obese CVD patients than their leaner counterparts. Moreover, the worst outcomes
are often incurred by underweight CVD patients, followed by those of normal
weight or severely obese. The obesity paradox is now a well-established
phenomenon across different types of CVD, and it occurs regardless of age and
ethnicity of patients, and severity of CVD. Physical inactivity and low
cardiorespiratory fitness (CRF) have long been recognized as major risk factors
for CVD. In contrast, high levels of physical activity (PA) and CRF largely
neutralize the adverse effects of excess adiposity and other traditional CVD risk
factors, including hypertension, metabolic syndrome, and type-2 diabetes. Higher
CRF also results in better CVD outcomes across different BMI groups and
significantly alters the obesity paradox in patients with HF and CHD. Prognostic
benefits of overweight/obesity tend to be limited to unfit patients with HF and
CHD, and the obesity paradox usually disappears with improved levels of CRF.
Nevertheless, increased PA and exercise training, to maintain or improve CRF, are
effective, safe, and proven strategies for primary and secondary prevention of
CVD in all weight groups. In this review, we discuss the current concepts of
individual and combined contributions of fatness and fitness to CVD risk and
prognosis. We then examine the influence of fitness on the obesity paradox in
individuals with CVD.
PMID- 28502850
TI - Cost-Effectiveness of a Bronchial Genomic Classifier for the Diagnostic
Evaluation of Lung Cancer.
AB - INTRODUCTION: The use of a bronchial genomic classifier has been shown to improve
the diagnostic accuracy of bronchoscopy for suspected lung cancer by identifying
patients who may be more suitable for radiographic surveillance as opposed to
invasive procedures. Our objective was to assess the cost-effectiveness of
bronchoscopy plus a genomic classifier versus bronchoscopy alone in the
diagnostic work-up of patients at intermediate risk for lung cancer. METHODS: A
decision-analytic Markov model was developed to project the costs and effects of
two competing strategies by using test performance from the Airway Epithelial
Gene Expression in the Diagnosis of Lung Cancer-1 and Airway Epithelial Gene
Expression in the Diagnosis of Lung Cancer-2 studies. The diagnostic accuracy of
noninvasive and invasive follow-up, as well as associated adverse event rates,
were derived from published literature. Procedure costs were based on claims data
and 2016 inpatient and outpatient reimbursement amounts. The model projected the
number of invasive follow-up procedures, 2-year costs and quality-adjusted life
years (QALYs) by strategy, and resulting incremental cost-effectiveness ratio
discounted at 3% per annum. RESULTS: Use of the genomic classifier reduced
invasive procedures by 28% at 1 month and 18% at 2 years, respectively. Total
costs and QALY gain were similar with classifier use ($27,221 versus $27,183 and
1.512 versus 1.509, respectively), resulting in an incremental cost-effectiveness
ratio of $15,052 per QALY. CONCLUSIONS: Our analysis suggests that the use of a
genomic classifier is associated with meaningful reductions in invasive
procedures at about equal costs and is therefore a high-value strategy in the
diagnostic work-up of patients at intermediate risk of lung cancer.
PMID- 28502851
TI - Inhibitory effect of alliin from Allium sativum on the glycation of superoxide
dismutase.
AB - Inhibition of glycation is an important approach for alleviating diabetic
complications. Alliin, the most abundant sulphur compound in garlic has been
demonstrated to possess antidiabetic activity. However, there is no scientific
evidence supporting its antiglycating activity. The objective of this study was
to determine the inhibitory effect of alliin on glucose and methyglyoxal (MG)
induced glycation of an important antioxidant enzyme, superoxide dismutase (SOD).
Glycation of SOD resulted in a decrease in enzyme activity, fragmentation/cross
linking, reduced cross-reactivity with anti-SOD antibodies, both tertiary and
secondary structural changes, and formation of AGEs and fibrils. Alliin offered
protection against glucose or MG induced glycation of SOD. The antiglycating
potential of alliin appears to be comparable with that of quercetin which is
reported to be a potent natural inhibitor of glycation. Alliin has a good
antiglycating effect and hence is expected to have therapeutic potential in the
prevention of glycation-mediated diabetic complications.
PMID- 28502852
TI - Effect of modification with 1,4-alpha-glucan branching enzyme on the rheological
properties of cassava starch.
AB - Steady and dynamic shear measurements were used to investigate the rheological
properties of cassava starches modified using the 1,4-alpha-glucan branching
enzyme (GBE) from Geobacillus thermoglucosidans STB02. GBE treatment lowered the
hysteresis loop areas, the activation energy (Ea) values and the parameters in
rheological models of cassava starch pastes. Moreover, GBE treatment increased
its storage (G') and loss (G") moduli, and decreased their tan delta (ratio of
G"/G') values and frequency-dependencies. Scanning electron microscopic studies
showed the selective and particular attack of GBE on starch granules, and X-ray
diffraction analyses showed that GBE treatment produces significant structural
changes in amylose and amylopectin. These changes demonstrate that GBE
modification produces cassava starch with a more structured network and improved
stability towards mechanical processing. Differential scanning calorimetric
analysis and temperature sweeps indicated greater resistance to granule rupture,
higher gel rigidity, and a large decrease in the rate of initial conformational
ordering with increasing GBE treatment time. Pronounced changes in rheological
parameters revealed that GBE modification enhances the stability of cassava
starch and its applicability in the food processing industry.
PMID- 28502854
TI - Characterization of a bi-functional cellulase produced by a gut bacterial
resident of Rosaceae branch borer beetle, Osphranteria coerulescens (Coleoptera:
Cerambycidae).
AB - A cellulolytic bacterium was obtained from the digestive tract of Osphranteria
coerulescens. The breakdown of woody and cellulosic substances by this insect may
be relative in part to its symbiont bacteria. Under optimal cultural conditions
the novel isolate produced 5.35U/ml cellulase after 72h. The enzyme was purified
to 36 fold with a 0.59% yield and showed a specific activity of 9.0U/mg. It
presented its maximum activity at 60 degrees C and pH 5, while it was stable in a
wide range of temperature from 20 to 60 degrees C and pH from 5 to 10. The
purified enzyme had a molecular weight of 42.50kDa based on SDS-PAGE and zymogram
analyses. It demonstrated high ions and solvent stability and its activity was
stimulated by Mn2+, Na+, DMSO and chloroform. The enzyme could hydrolyze CMC,
avicel, cellulose and sawdust. TLC analysis represented the cellobiose as the
hydrolytic product of CMC. With regard to endo/exo glucanase activity and wide
pH, temperature and solvent stability, it has potential for industrial
application.
PMID- 28502853
TI - Cloning, characterization, and function of MyD88 in silvery pomfret (Pampus
argenteus) in response to bacterial challenge.
AB - Myeloid differentiation factor 88 (MyD88) is a key and universal downstream
adapter for most Toll-like receptors (TLRs) and plays an important role in both
the innate and adaptive immune response. In this study, the full-length cDNA of
MyD88 (PAMyD88) from silvery pomfret (Pampus argenteus) was cloned and
characterized. The PAMyD88 cDNA is 1545bp in length and contains an 876bp open
reading frames (ORF). Multiple sequence alignment and phylogenetic tree analyzes
revealed that the amino acid sequence of PAMyd88 was homologous to a variety of
previously MyD88 molecules characterized from other species. The quantitative
real-time reverse transcription-PCR analysis showed that the PAMyD88 mRNA was
broadly expressed in all examined tissues, with higher levels observed in the
immune-relevant organs. The results showed a significant up-regulation of the
TLR2 and PAMyD88 transcript levels in response to L. plantarum and C. butyricum
and a substantial expression level of TLR4 and PAMyD88 induced by V. anguillarum.
Additionally, a challenge with V. anguillarum resulted in significant apoptosis,
whereas the L. plantarum and C. butyricum induced only low levels of apoptosis.
These data provide insight into the roles of PAMyD88 in the TLR signaling pathway
in response to probiotic and pathogenic bacteria in silvery pomfrets.
PMID- 28502855
TI - Caesalpinia bonduc serine proteinase inhibitor CbTI-2: Exploring the
conformational features and antimalarial activity.
AB - Seeds of tropical legumes posses a repertoire of proteinase inhibitors (PI) and
the current study highlights some structural/functional features of a strong
serine PI from the seeds of Caesalpinia bonduc (CbTI-2). Following purification,
N-terminal sequence of CbTI-2 revealed over 40% similarity with a few serine PIs
of Caesalpinioideae subfamily. Upon exposure to metal ions and ionic/non ionic
surfactants, CbTI-2 showed immense variation in the levels of antitryptic
activity. Exposure of CbTI-2 to 1,4-Dithiothreitol, Guanidinium HCl, H2O2 and
Dimethyl sulfoxide led to a steady loss of inhibitory activity. Chemical
modification of amino acids suggested an arginine as the active site residue.
Circular Dichroism spectrum of native CbTI-2 revealed an unordered state.
Secondary structure composition of CbTI-2 following exposure to extreme
conditions (heat, acidic/alkaline environment, Guanidine hydrochloride and DTT)
showed considerable perturbations that caused severe loss of antiproteolytic
activity. DLS studies yielded a hydrodynamic radius of ~2.2nm for CbTI-2 and also
reconfirmed 1:1 stoichiometry for the trypsin-CbTI-2 complex. Initial studies
indicated CbTI-2 to be a potent antiplasmodial agent by being highly toxic
towards growth, schizont rupture process and erythrocytic invasion of Plasmodium
falciparum.
PMID- 28502856
TI - DNA chip based sensor for amperometric detection of infectious pathogens.
AB - Several infectious pathogens are found in human whose detection is essential for
rapid cure of diseases. The most commonly found pathogen in human is
Streptococcus pyogenes which leads to a wide range of infections from mild
pharyngitis to rheumatic heart disease. An ultrasensitive DNA chip based sensor
was developed for quick identification of pathogen S. pyogenes from patient
throat swab samples. The amperometric response was measured after hybridization
of specific probe with single stranded genomic DNA (ssG-DNA) from the patient
samples. The DNA chip was characterized by FTIR, SEM and validated with suspected
patient real samples. The sensitivity of the DNA chip based sensor was found
951.34(MUA/cm2)/ng DNA and lower limit of detection (LOD) was 130fg/6MUL samples.
The DNA chip based sensor is highly specific and takes only 30min for
identification of specific pathogen.
PMID- 28502857
TI - Spirostanol saponins from Ypsilandra parviflora induce platelet aggregation.
AB - Phytochemical investigation on the whole plants of Ypsilandra parviflora led to
the isolation of seven new spirostanol saponins, named ypsiparosides A-G,
together with 14 known saponins. Their structures were unambiguously established
based on extensive spectroscopic evidence and chemical methods. The induced
rabbit platelet aggregation activities of the isolates were tested. Compounds 4,
15, and 17 showed maximal platelet aggregation rates ranging from 43 to 55% at a
concentration of 300MUg/mL. Further experiments exhibited that compounds 4, 15,
and 17 possessed EC50 values of 642.9, 95.3, and 300.8MUg/mL, respectively.
PMID- 28502858
TI - Absolute quantification of cholesteryl esters using liquid chromatography-tandem
mass spectrometry uncovers novel diagnostic potential of urinary sediment.
AB - BACKGROUND: Urine has been utilized as a source of biomarkers in renal disease.
However, urinary lipids have not attracted much attention so far. Here we studied
urinary cholesteryl ester (CE) and its relevance in renal disease. METHODS:
Quantitative analysis of CE molecular species in serum, urinary supernatant, and
urinary sediment from patients with renal disease (N=64) and non-renal disease
(N=23) was carried out using liquid chromatography-tandem mass spectrometry (LC
MS/MS) and deuterated CEs as internal standards. RESULTS: Validation study showed
good precision and accuracy of LC-MS/MS. Many CE species were detected in the
urinary sediment and supernatant in the renal disease group, whereas only a few
CE species were detected in the other group. In the renal disease group, the sum
of the concentrations of all CE species showed a significant correlation between
the sediment and the supernatant from urinary samples (r=0.876, p<0.001);
however, the composition of CEs was significantly different between them.
Further, the composition of CEs of the supernatant was similar to that of the
serum. CONCLUSIONS: Our LC-MS/MS analysis uncovered a distinct CE profile in
urinary sediment from patients with renal disease, suggesting a possible
contribution of CEs in urothelial cells to the development of renal disease.
PMID- 28502860
TI - Structure-activity relationship of brassinosteroids and their agricultural
practical usages.
AB - Brassinosteroids (BRs) control several important agronomic traits, such as
strengthening resistance to diverse adversity, improving the quality, and
increasing crop yield. Their chemical structures and varieties, specific methods
for the evaluation of bioactivities, structure-activity relationships, potential
novel compounds, and practical agricultural uses were summarized. The findings
allow the examination of brassinosteroids in two important issues: 1) Do the
results of different bioevaluation protocols provide similar activities for BRs?
and 2) which bioevaluated compounds would proof to have a greater potential for
application in agricultural usages?
PMID- 28502859
TI - The significance of estradiol metabolites in human corpus luteum physiology.
AB - The human corpus luteum (CL) is a temporary endocrine gland derived from the
ovulated follicle. Its formation and limited lifespan is critical for steroid
hormone production required to support menstrual cyclicity, endometrial
receptivity for successful implantation, and the maintenance of early pregnancy.
Endocrine and paracrine-autocrine molecular mechanisms associated with
progesterone production throughout the luteal phase are critical for the
development, maintenance, regression, and rescue by hCG which sustains CL
function into early pregnancy. However, the signaling systems driving the
regression of the primate corpus luteum in non-conception cycles are not well
understood. Recently, there has been interest in the functional roles of
estradiol metabolites (EMs), mostly in estrogen-producing tissues. The human CL
produces a number of EMs, and it has been postulated that the EMs acting via
paracrine-autocrine pathways affect angiogenesis or LH-mediated events. The
present review describes advances in understanding the role of EMs in the
functional lifespan and regression of the human CL in non-conception cycles.
PMID- 28502861
TI - Analysis of testosterone fatty acid esters in the digestive gland of mussels by
liquid chromatography-high resolution mass spectrometry.
AB - Several studies have indicated that up to 70% of the total steroids detected in
molluscs are in the esterified form and that pollutants, by modifying the
esterification of steroids with fatty acids, might act as endocrine disrupters.
However, despite the strong physiological significance of this process, there is
almost no information on which fatty acids form the steroid esters and how this
process is modulated. This study (a) investigates the formation of fatty acid
esters of testosterone in digestive gland microsomal fractions of the mussel
Mytilus galloprovincialis incubated with either palmitoly-CoA or CoA and ATP, and
(b) assesses whether the endocrine disruptor tributyltin (TBT) interferes with
the esterification of testosterone. Analysis of testosterone esters was performed
by liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). When
microsomal fractions were incubated with testosterone and palmitoly-CoA, the
formation of testosterone palmitate was detected. However, when microsomes were
incubated with CoA and ATP, and no exogenous activated fatty acid was added, the
synthesis of 16:0, 16:1, 20:5 and 22:6 testosterone esters was observed. The
presence of 100uM TBT in the incubation mixture did not significantly alter the
esterification of testosterone. These results evidence the conjugation of
testosterone with the most abundant fatty acids in the digestive gland microsomal
fraction of mussels.
PMID- 28502862
TI - 11 beta-hydroxysteroid dehydrogenase 2 promoter methylation is associated with
placental protein expression in small for gestational age newborns.
AB - Small for gestational age infants have greater risk of developing metabolic
diseases in adult life. It has been suggested that low birth weight may result
from glucocorticoid excess in utero, a key mechanism in fetal programming. The
placental enzyme 11-beta hydroxysteroid dehydrogenase type 2 (11beta-HSD2,
HSD11B2 gene) acts as a barrier protecting the fetus from maternal corticosteroid
deleterious effects. Low placental 11beta-HSD2 transcription and activity have
been associated with low birth weight, yet the mechanism regulating its protein
expression is not fully understood. In the present study we aimed to analyze
11beta-HSD2 protein expression in placentas of adequate and small for gestational
age (AGA and SGA, respectively) newborns from healthy mothers, and to explore
whether 11beta-HSD2 protein expression could be modulated by DNA methylation.
11beta-HSD2 protein levels were measured by western blot in placental biopsies
from term AGA and SGA infants (n=10 per group). DNA methylation was profiled both
globally and in the HSD11B2 promoter by liquid chromatography with UV detection
and methylation-specific melting curve analysis, respectively. We found lower
placental 11beta-HSD2 protein expression and higher HSD11B2 promoter methylation
in SGA compared to AGA. Promoter methylation was inversely correlated with both
protein expression and, importantly, birth weight. No changes in global placental
methylation were found. In conclusion, lower 11beta-HSD2 protein expression is
associated with higher HSD11B2 promoter methylation, correlating with birth
weight in healthy pregnancy. Our data support the role of 11beta-HSD2 in
determining birth weight, providing evidence of its regulation by epigenetic
mechanisms, which may affect postnatal metabolic disease risk.
PMID- 28502863
TI - Synthesis of 16alpha-amino-pregnenolone derivatives via ionic liquid-catalyzed
aza-Michael addition and their evaluation as C17,20-lyase inhibitors.
AB - Aza-Michael addition of 16-dehydropregnenolone was studied in the presence of a
basic ionic liquid, [DBU][OAc] as catalyst and solvent. The reaction was carried
out using different primary and secondary amines as N-nucleophiles. The products
were obtained in moderate to good yields and were characterized by 1H and 13C
NMR, MS and IR. The ionic liquid was found to be an efficient and recyclable
catalyst that was reused five times. The products were investigated for the
inhibition of in vitro C17,20-lyase activity and displayed moderate inhibitory
effect.
PMID- 28502864
TI - Chagas disease in Europe: A review for the internist in the globalized world.
AB - Chagas disease (CD) or American trypanosomiasis identified in 1909 by Carlos
Chagas, has become over the last 40years a global health concern due to the huge
migration flows from Latin America to Europe, United States, Canada and Japan. In
Europe, most migrants from CD-endemic areas are concentrated in Spain, Italy,
France, United Kingdom and Switzerland. Pooled seroprevalence studies conducted
in Europe show an overall 4.2% prevalence, with the highest infection rates
observed among individuals from Bolivia (18.1%). However, in most European
countries the disease is neglected with absence of screening programmes and low
access to diagnosis and treatment. Physicians working in Europe should also be
aware of the risk of autochthonous transmission of Trypanosoma cruzi to newborns
by their infected mothers and to recipients of blood or transplanted organs from
infected donors. Finally, physicians should be able to recognize and treat the
most frequent and serious complications of chronic Chagas disease, namely
cardiomyopathy, megacolon and megaesophagus. This review aims to highlights the
problem of CD in Europe by reviewing papers published by European researchers on
this argument, in order to raise the awareness of internists who are bound to
increasingly encounter patients with the disease in their routine daily
activities.
PMID- 28502865
TI - Cartilage oligomeric matrix protein on the spot for liver fibrosis evaluation:
Too early or too late?
PMID- 28502866
TI - What is inappropriate hospital use for elderly people near the end of life? A
systematic review.
AB - BACKGROUND: Older people with advance chronic illness use hospital services
repeatedly near the end of life. Some of these hospitalizations are considered
inappropriate. AIM: To investigate extent and causes of inappropriate hospital
admission among older patients near the end of life. METHODS: English language
publications in Medline, EMBASE, PubMed, Cochrane library, and the grey
literature (January 1995-December 2016) covering community and nursing home
residents aged >=60years admitted to hospital. OUTCOMES: measurements of
inappropriateness. A 17-item quality score was estimated independently by two
authors. RESULTS: The definition of 'Inappropriate admissions' near the end of
life incorporated system factors, social and family factors. The prevalence of
inappropriate admissions ranged widely depending largely on non-clinical reasons:
poor availability of alternative sites of care or failure of preventive actions
by other healthcare providers (1.7-67.0%); family requests (up to 10.5%); or too
late an admission to be of benefit (1.7-35.0%). The widespread use of subjective
parameters not routinely collected in practice, and the inclusion of non-clinical
factors precluded the true estimation of clinical inappropriateness. CONCLUSIONS:
Clinical inappropriateness and system factors that preclude alternative community
care must be measured separately. They are two very different justifications for
hospital admissions, requiring different solutions. Society has a duty to ensure
availability of community alternatives for the management of ambulatory-sensitive
conditions and facilitate skilling of staff to manage the terminally ill in non
acute settings. Only then would the evaluation of local variations in clinically
inappropriate admissions and inappropriate length of stay be possible to
undertake.
PMID- 28502867
TI - Screening for occult cancer in idiopathic venous thromboembolism - Systemic
review and meta-analysis.
AB - BACKGROUND: Idiopathic venous thromboembolism (VTE) may be associated with an
occult malignancy. Early detection of cancer might be translated to a better
prognosis for these patients. However, the efficacy of extensive screening for
cancer in patients with idiopathic VTE is controversial. MATERIALS AND METHODS:
Systemic review and meta-analysis of all available prospective trials comparing
extensive to limited screening for occult malignancies in patients with
idiopathic VTE. PRIMARY OUTCOME: all-cause mortality. SECONDARY OUTCOMES: cancer
related mortality, early cancer diagnosis, cancer diagnosis at the end of follow
up and cancer diagnosis at an early stage. Risk ratios (RR) with 95% confidence
intervals (CIs) were estimated and pooled. RESULTS: The study included five
trials and 2287 patients. Extensive screening did not affect all-cause mortality
at the end of follow up [RR 0.86 (95% CI 0.58-1.27)] or cancer-related mortality
[RR 0.93 (95% CI 0.54-1.58)]. Yet, it yielded more diagnoses of cancer [RR 2.17
(95% CI 1.42-3.32)]. Rates of cancer diagnosis at an early stage did not differ
statistically between the two groups [RR 1.49 (95% CI 0.86-2.56)]. However,
analysis of the randomized controlled trials alone showed a tendency towards
early stage cancer at diagnosis in extensive screening group in, with results
almost statistically significant [RR 2.14 (95% CI 0.98-4.67), p=0.06].
CONCLUSIONS: Extensive screening for malignancy after idiopathic VTE does not
affect mortality rates. Yet, it yields more cancer diagnoses shortly after the
VTE event. Further research is needed to determine whether extensive screening
might be proper for specific high risk populations.
PMID- 28502868
TI - No pain, no gain: Male plasticity in burrow digging according to female rejection
in a sand-dwelling wolf spider.
AB - Behavioral plasticity allows individuals to reversibly respond to short-term
variations in their ecological and social environment in order to maximize their
fitness. Allocosa senex is a burrow-digging spider that inhabits the sandy coasts
of South America. This species shows a reversal in typical sex roles expected in
spiders: females are wanderers that visit males at their burrows and initiate
courtship. They prefer males with long burrows for mating, and males prefer
virgin over mated females. We tested whether female sexual rejection induced
males to enlarge their burrows and if female reproductive status affected males'
responses. We exposed males who had constructed burrows to: a) virgin females or
b) mated females, (n=16 for each category). If female rejection occurred, we
repeated the trial 48h later with the same female. As control, we maintained a
group of males without female exposure (unexposed group, n=32). Rejected males
enlarged their burrows more frequently and burrows were longer compared to
unexposed males. However, frequency and length of enlargement did not differ
according to female reproductive status. Males of A. senex showed plasticity in
digging behavior in response to the availability of females, as a way to maximize
the possibilities of future mating.
PMID- 28502869
TI - Comparative analysis of osteoblast gene expression profiles and Runx2 genomic
occupancy of mouse and human osteoblasts in vitro.
AB - Fast progress of the next generation sequencing (NGS) technology has allowed
global transcriptional profiling and genome-wide mapping of transcription factor
binding sites in various cellular contexts. However, limited number of replicates
and high amount of data processing may weaken the significance of the findings.
Comparative analyses of independent data sets acquired in the different
laboratories would greatly increase the validity of the data. Runx2 is the key
transcription factor regulating osteoblast differentiation and bone formation. We
performed a comparative analysis of three published Runx2 data sets of chromatin
immunoprecipitation followed by deep sequencing (ChIP-seq) analysis in
osteoblasts from mouse and human origin. Moreover, we assessed the similarity of
the corresponding transcription data of these studies available online. The ChIP
seq data analysis confirmed general features of Runx2 binding, including location
at genic vs intergenic regions and abundant Runx2 binding on promoters of the
highly expressed genes. We also found high frequency of Runx2 DNA binding without
a consensus Runx2 motif at the binding site. Importantly, mouse and human Runx2
showed moderately similar binding patterns in terms of peak-associated closest
genes and their associated genomic ontology (GO) pathways. Accordingly, the gene
expression profiles were highly similar and osteoblastic phenotype was prominent
in the differentiated stage in both species. In conclusion, ChIP-seq method shows
good reproducibility in the context of mature osteoblasts, and mouse and human
osteoblast models resemble each other closely in Runx2 binding and in gene
expression profiles, supporting the use of these models as adequate tools in
studying osteoblast differentiation.
PMID- 28502870
TI - Comparison of longevity and clinical outcomes of implantable cardioverter
defibrillator leads among manufacturers.
AB - BACKGROUND: An early failure of the Biotronik Linox S/SD implantable cardioverter
defibrillator (ICD) lead has been reported. We have also experienced several
cases with early failure of Linox leads. OBJECTIVE: Our aim was to assess the
longevity of Linox S/SD (Biotronik, Berlin, Germany) compared with Sprint Fidelis
(Medtronic, Minneapolis, MN), Sprint Quattro (Medtronic), and Endotak Reliance
(Boston Scientific, Natick, Massachusetts) leads. METHODS: We retrospectively
reviewed patients who had undergone implantation of Linox S/SD (n = 90), Sprint
Fidelis (n = 37), Sprint Quattro (n = 27), or Endotak Reliance (n = 50) leads
between June 2000 and December 2013 at our hospital. Variables associated with
lead failure were assessed by the Kaplan-Meier method and Cox survival modeling.
RESULTS: Failure rates of Linox, Sprint Fidelis, and Endotak leads were 3.2%/year
(7-year survival rate, 81.0%), 3.4%/year (7-year survival rate, 77.2%), and
0.61%/year (7-year survival rate, 95.8%), respectively. No lead failure was found
with Sprint Quattro leads. The survival probability of Linox leads was
significantly lower than that of Endotak leads (P = .049) and comparable to that
of Sprint Fidelis leads (P = .69). In univariate analysis, age was the only
predictor of Linox lead failure. Patients <58 years old were at significantly
increased risk of lead failure compared with patients >=58 years old (hazard
ratio, 9.0; 95% confidence interval, 1.13-71.3; P = .037). CONCLUSION: In our
single-center experience, the survival rate of Linox leads was unacceptably low.
The only predictor of Linox lead failure was age at implantation. This is the
first description of a lower survival rate for Linox leads in an Asian
population.
PMID- 28502871
TI - A leadless pacemaker in the real-world setting: The Micra Transcatheter Pacing
System Post-Approval Registry.
AB - BACKGROUND: First-in-man studies of leadless pacemakers have demonstrated high
rates of implant success, and safety and efficacy objectives were achieved.
Outside of the investigational setting, there are concerns, particularly over
cardiac effusion and perforation, device dislodgement, infection, telemetry, and
battery issues. OBJECTIVE: The acute performance of the Micra transcatheter
pacemaker from a worldwide Post-Approval Registry is reported. METHODS: The
registry is an ongoing prospective single-arm observational study designed to
assess the safety and effectiveness of Micra in the post-approval setting. The
safety end point was system- or procedure-related major complications at 30 days
post implant. We compared the major complication rate with that of the 726
patients from the investigational study. Electrical performance was also
characterized. RESULTS: The device was successfully implanted in 792 of 795
registry patients (99.6%) by 149 implanters at 96 centers in 20 countries.
Through 30 days post implant, a total of 13 major complications occurred in 12
patients, for a major complication rate of 1.51% (95% confidence interval, 0.78%
2.62%). Major complications included cardiac effusion/perforation (1, 0.13%),
device dislodgement (1, 0.13%), and sepsis (1, 0.13%). After adjusting for
baseline differences, the rate of major complications in the registry trended
lower than the investigational trial (odds ratio, 0.58, 95% confidence interval,
0.27-1.25; P = .16). Early pacing capture thresholds were low and stable.
CONCLUSION: Performance of the Micra transcatheter pacemaker in a real-world
setting demonstrates a high rate (99.6%) of implant success and low rate (1.51%)
of major complications through 30 days post implant. In particular, the rates of
pericardial effusion, device dislodgement, and infection were low, reinforcing
the positive results seen in the investigational study.
PMID- 28502872
TI - Subcutaneous implantable cardioverter-defibrillator Post-Approval Study: Clinical
characteristics and perioperative results.
AB - BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) was
developed to reduce short- and long-term complications associated with
transvenous ICD leads. Early multicenter studies included younger patients with
less left ventricular systolic dysfunction and fewer comorbidities than cohorts
with traditional ICD. OBJECTIVE: The purpose of this study was to characterize
patient selection and the acute performance of the S-ICD in a contemporary real
world setting. METHODS: The S-ICD Post-Approval Study is a prospective registry
involving 86 US centers. Patients were enrolled if they met criteria for S-ICD
implantation, passed an electrocardiogram screening test, and had a life
expectancy of >1 year. Analyses of descriptive statistics, Kaplan-Meier time to
event, and multivariate logistic regression were performed. RESULTS: The study
includes 1637 patients who underwent S-ICD implantation. The cohort included
68.6% (1123/1637) male patients, and 13.4% (220/1636) were receiving dialysis for
end-stage renal disease. The mean age was 52 +/- 15 years, with a mean left
ventricular ejection fraction of 32.0% +/- 14.6%. Electrocardiogram screening was
successful for at least 1, 2, or 3 vectors in 100%, 93.8%, and 51.4% of patients,
respectively. Medical imaging (65.1%, 1065/1636) and general anesthesia (64.1%,
1048/16) were used in a majority of patients, and 52.2% (855/1637) were implanted
with the 2-incision technique. Induced ventricular tachycardia/ventricular
tachycardia was successfully converted in 98.7% (1394/1412) of patients. The 30
day complication-free rate was 96.2%. Predictors of complications included
diabetes, younger age, and higher body mass index. CONCLUSION: Contemporary US
patients with S-ICD have more comorbidities than do previous cohorts with S-ICD,
but they are younger with more end-stage renal disease than do patients with
transvenous ICD. Implantation success is high, and short-term complication rates
are acceptable.
PMID- 28502874
TI - Aerobic vaginitis: no longer a stranger.
AB - Aerobic vaginitis (AV) is the name given in 2002 to a vaginal infectious entity
which was not recognized as such before. It is characterized by abnormal
(dysbiotic) vaginal microflora containing aerobic, enteric bacteria, variable
levels of vaginal inflammation and deficient epithelial maturation. Although AV
and bacterial vaginosis (BV) share some characteristics, such as a diminished
number or absence of lactobacilli, increased discharge (fishy smelling in BV,
while in severe forms of AV, a foul, rather rotten smell may be present) and
increased pH (often more pronounced in AV), there are also striking differences
between the two. There is no inflammation in women with BV, whereas the vagina of
women with AV often appears red and edematous, and may even display small
erosions or ulcerations. The color of the discharge in BV is usually whitish or
gray and of a watery consistency, whereas in AV it is yellow to green and rather
thick and mucoid. Women with BV do not have dyspareunia, while some women with
severe AV do. Finally, the microscopic appearance differs in various aspects,
such as the presence of leucocytes and parabasal or immature epithelial cells in
AV and the absence of the granular aspect of the microflora, typical of BV.
Despite all these differences, the distinction between AV and BV was not
recognized in many former studies, leading to incomplete and imprecise diagnostic
workouts and erroneous management of patients in both clinical and research
settings. The prevalence of AV ranges between 7 and 12%, and is therefore less
prevalent than BV. Although still largely undiagnosed, many researchers and
clinicians increasingly take it into account as a cause of symptomatic vaginitis.
AV can co-occur with other entities, such as BV and candidiasis. It can be
associated with dyspareunia, sexually transmitted infections (such as human
papilloma virus, human immunodeficiency virus, Trichomonas vaginalis and
Chlamydia trachomatis), chorioamnionitis, fetal infection, preterm birth and
cervical dysplasia. Many other possible pathological associations are currently
under investigation. The diagnosis of AV is made using wet mount microscopy,
ideally using phase contrast. An AV score is calculated, according to:
lactobacillary grade, presence of inflammation, proportion of toxic leucocytes,
characteristics of the microflora and presence of immature epithelial cells. To
circumvent the hurdle of microscopic investigation, some groups have begun to
develop nucleic-acid-based and enzymatic diagnostic tests, but the detailed
information obtained with phase contrast microscopy is irreplaceable. The best
treatment is not yet fully determined, but it must be tailored according to the
microscopic findings and the patient's needs. There is a role for local estrogen
therapy, corticosteroids, antimicrobials and probiotics. Further research will
reveal more precise data on diagnosis, pathogenesis, management and prevention.
PMID- 28502873
TI - Synchronization as a mechanism for low-energy anti-fibrillation pacing.
AB - BACKGROUND: Low-energy anti-fibrillation pacing (LEAP) has been suggested as an
alternative treatment in symptomatic fibrillation patients. It significantly
lowers the energy required compared with standard 1-shock defibrillation.
OBJECTIVE: In this study, we investigated the mechanism of arrhythmia termination
by LEAP and systematically analyzed the influence of shock period and timing on
the success rate of LEAP. METHODS: We induced atrial and ventricular fibrillation
in isolated canine hearts and applied LEAP and standard 1-shock defibrillation to
terminate the arrhythmia. We simulated the arrhythmia and LEAP using a 2
dimensional bidomain human atrial model. RESULTS: The ex vivo experiments showed
successful termination of atrial fibrillation and ventricular fibrillation using
LEAP, with an average 88% and 81% energy reduction, respectively, and both
experiments and simulations verified that synchronization from virtual electrodes
is the key mechanism for termination of arrhythmia by LEAP using modified
Kuramoto phase plots and fraction of tissue excited (FTE) plots. We also observed
in simulations that LEAP is more effective when the shock period is close to the
dominant period and the first shock is delivered when FTE is decreasing.
CONCLUSIONS: Our results support synchronization as the mechanism for arrhythmia
termination by LEAP, and its effectiveness can be improved by adjusting shock
period and timing.
PMID- 28502875
TI - Efficacy of photodynamic therapy versus antibiotics as an adjunct to scaling and
root planing in the treatment of periodontitis: A systematic review and meta
analysis.
AB - BACKGROUND: To determine whether treatment with antimicrobial photodynamic
therapy (aPDT) as an adjunct to scaling and root planing (SRP) yield better
clinical periodontal outcomes than antibiotics (AB) as adjunct to SRP in
periodontitis. METHODS: Electronic searches were conducted in databases (MEDLINE,
PubMed, EMBASE, SCOPUS, Cochrane Central Register of Controlled Trials and
Cochrane Oral Health Group Trials Register databases) up to and including April
2017. RESULTS: Five randomized trials were included. All studies used the
combined approach aPDT+SRP and AB+SRP in the test and control group respectively.
The follow up period ranged from 12 to 48 weeks. All studies used diode lasers.
The wavelengths, power density and duration of irradiation used were 670
nanometre, 75 milliwatts per square centimeters and 60s respectively. None of the
studies showed additional benefits of aPDT at follow up. Considering the effects
of adjunctive aPDT as compared to AB, a high degree of heterogeneity for
periodontal probing depth (PPD) (p<0.0001, I2=87.47%) was noticed among both the
groups. Meta-analysis showed significant clinical attachment level (CAL) gain
(WMD=0.60, 95% CI=0.25 to 0.95, p=0.001), and not PPD reduction (WMD=0.67, 95%
CI=-0.36 to 1.71, p=0.204) for aPDT as compared to AB at follow up. CONCLUSION:
It remains debatable whether aPDT is more effective as compared to adjunctive AB
in the treatment of periodontitis, given that the scientific evidence is weak.
Precautions must be exercised when interpreting the results of this study due to
the small sample size and high heterogeneity among studies.
PMID- 28502876
TI - Novel strategy in giant cutaneous squamous cell carcinoma treatment: The case
experience with a combination of photodynamic therapy and surgery.
AB - The treatment for giant cutaneous squamous cell carcinoma (cSCC) is challenging.
Here, we reported that a 90-year-old patient with giant cSCC was successfully
treated through combination of surgery and photodynamic therapy (PDT). Due to the
advanced patient age, large tumor area, and deep infiltration, radical surgery
cannot be performed initially. After in situ resection, five rounds of topical 5
aminolevulinic acid PDT were continuously performed. The surgical wound was
healed five months after resection. Seven months after initial resection, the
residual tumor was resected by a radical surgery. The patient was followed up for
six months after the radical surgical resection and showed no tumor recurrence.
This case suggested that initial utmost resection for main body of tumor,
decreasing the tumor boundary by PDT treatment and the sequential treatment
regimen of radical surgery can be an effective therapeutic schedule for
refractory and giant cSCC.
PMID- 28502877
TI - Irradiance dependence of the conduction block of an in vitro cardiomyocyte wire.
AB - BACKGROUND: To obtain therapeutic condition precisely by in vitro experiment, we
studied the irradiance dependence of the electrical conduction blockage caused by
a photodynamic reaction using a high extracellular concentration of talaporfin
sodium on a novel in vitro cardiomyocyte electrical conduction wire. METHODS: The
cardiomyocyte wires were constructed on patterned cultivation cover glass, which
had cultivation areas 60MUm in width, and a maximum length of 10mm. The
talaporfin sodium concentration was set to 20MUg/mL. The photodynamic reaction
with a high extracellular photosensitizer concentration was performed with a
short time interval (approximately 15min) between photosensitizer exposure and
irradiation. A 663-nm laser was applied to the cardiomyocyte wire, and the
irradiance was varied between 3 and 120mW/cm2. The cardiomyocyte electrical
conduction was evaluated using the cross-correlation function of intracellular
Ca2+ probe fluorescence brightness from an upper and lower section outside the
laser irradiation area of a wire every 10s, which lasted up to 600s. RESULTS: The
onset of electrical conduction blockage was defined by an 85% decrease in the
cross-correlation function, compared with its initial value. The time for the
electrical conduction blockage decreased from 600 to 300s as the irradiance was
increased. Also, the probability of electrical conduction blockage was found to
increase with increasing irradiance. CONCLUSIONS: We found a strong dependence on
the irradiance for the time and probability of electrical conduction blockage.
PMID- 28502878
TI - The Relationship Between Sensory Loss and Persistent Pain 1 Year After Breast
Cancer Surgery.
AB - : Moderate to severe persistent pain after breast cancer surgery (PPBCS) affects
10 to 20% of the patients. Sensory dysfunction is often concomitantly present
suggesting a neuropathic pain state. The relationship between various
postoperative pain states and sensory dysfunction has been examined using
quantitative sensory testing (QST), but only 2 smaller studies have examined
PPBCS and sensory dysfunction in the surgical area. The purpose of this
prospective study was to assess the relative importance of sensory function and
PPBCS. QST consisted of sensory mapping, tactile detection threshold, mechanical
pain threshold, and thermal thresholds. Two hundred ninety patients were enrolled
and results showed that 38 (13%) had moderate to severe pain and 246 (85%) had
hypoesthesia in the surgical area 1 year after surgery. Increased hypoesthesia
areas were associated with pain at rest as well as during movement (P = .0001).
Pain during movement was associated with a side-to-side difference of 140% (P =
.001) for tactile detection threshold and 40% (P = .01) for mechanical pain
threshold as well as increased thermal thresholds in the axilla (P > .001).
Logistic regression models controlling for confounders showed larger areas of
hypoesthesia as a significant risk factor, odds ratio 1.85 per 100 cm2 for pain
at rest and odds ratio 1.36 per 100 cm2 for pain during movement. PERSPECTIVE:
PPBCS is associated with increasing areas of hypoesthesia as well as
intraoperative nerve preservation. Thus, we hypothesize that PPBCS is associated
with an interaction between a peripheral nociceptive drive in macroscopically
preserved nerves and the central nervous system causing PPBCS as well as
hypoesthesia. QST may identify patients suitable for intervention.
PMID- 28502879
TI - Genetic deletion of P-glycoprotein alters stress responsivity and increases
depression-like behavior, social withdrawal and microglial activation in the
hippocampus of female mice.
AB - P-glycoprotein (P-gp) is an ABC transporter expressed at the blood brain barrier
and regulates the brain uptake of various xenobiotics and endogenous mediators
including glucocorticoid hormones which are critically important to the stress
response. Moreover, P-gp is expressed on microglia, the brain's immune cells,
which are activated by stressors and have an emerging role in psychiatric
disorders. We therefore hypothesised that germline P-gp deletion in mice might
alter the behavioral and microglial response to stressors. Female P-gp knockout
mice displayed an unusual, frantic anxiety response to intraperitoneal injection
stress in the light-dark test. They also tended to display reduced conditioned
fear responses compared to wild-type (WT) mice in a paradigm where a single
electric foot-shock stressor was paired to a context. Foot-shock stress reduced
social interaction and decreased microglia cell density in the amygdala which was
not varied by P-gp genotype. Independently of stressor exposure, female P-gp
deficient mice displayed increased depression-like behavior, idiosyncratic
darting behavior, age-related social withdrawal and hyperactivity, facilitated
sensorimotor gating and altered startle reactivity. In addition, P-gp deletion
increased microglia cell density in the CA3 region of the hippocampus, and the
microglial cells exhibited a reactive, hypo-ramified morphology. Further, female
P-gp KO mice displayed increased glucocorticoid receptor (GR) expression in the
hippocampus. In conclusion, this research shows that germline P-gp deletion
affected various behaviors of relevance to psychiatric conditions, and that
altered microglial cell activity and enhanced GR expression in the hippocampus
may play a role in mediating these behaviors.
PMID- 28502881
TI - Multilevel Schwab grade II osteotomies for sagittal plane correction in the
management of adult spinal deformity.
AB - BACKGROUND CONTEXT: Prior reports have compared posterior column osteotomies with
pedicle subtraction osteotomies in terms of utility for correcting fixed sagittal
imbalance in adolescent patients with deformity. No prior reports have described
the use of multilevel Smith-Petersen Osteotomies (SPOs) alone for surgical
correction in the adult spinal deformity (ASD) population. PURPOSE: The study
aimed to determine the utility of multilevel SPOs in the management of global
sagittal imbalance in ASD patients. STUDY DESIGN/SETTING: This is a retrospective
observational study at a single academic center. PATIENT SAMPLE: The sample
included 85 ASD patients. OUTCOME MEASURES: This is a radiographic outcomes
cohort study. METHODS: The radiographs of 85 ASD patients were retrospectively
evaluated before and after long-segment (>5 spinal levels) fusion and multilevel
SPO (>=3 levels) for sagittal imbalance correction. The number of osteotomies,
correction in regional lumbar lordosis (LL), and correction per osteotomy was
evaluated. Independent predictors of correction per SPO were evaluated with a
hierarchical linear regression analysis. RESULTS: Eighty-five patients (mean age:
67.5+/-11 years) were identified with ASD (372 SPOs). The mean preoperative
sagittal vertical axis (SVA) and T1 pelvic angle (TPA) were 8.16+/-6.75 cm and 25
degrees +/-13.23 degrees , respectively. The mean postoperative central sacral
vertical line (CSVL) and SVA were 0.67+/-0.70 cm and 1.29+/-5.41 cm,
respectively. The mean improvement in SVA was 6.29 cm achieved with a correction
of approximately 5.05 degrees per SPO. The mean LL restoration was 20.3 degrees
+/-13.9 degrees , and 33(39%) patients achieved a final pelvic incidence minus
lumbar lordosis (PI-LL) <=10 degrees . Fifty-four (64%) achieved a postoperative
PI-LL <=15 degrees , 75 (88%) with a PI-LL <=20 degrees , and 85 (100%) achieved
a PI-LL <=25 degrees . Correction per SPO was similar regardless of prior fusion
(4.87 degrees vs. 5.72 degrees for revisions, p=.192). In a subgroup analysis
of SVA greater than 10 cm, there was no significant difference in the final LL,
thoracic kyphosis, PI-LL, SVA, CSVL, and TPA, as compared with SVA <10 cm. The LL
was the only independent predictor of osteotomy correction per level (LL: beta
coefficient=-0.108, confidence interval: -0.141 to 0.071, p<.0001). CONCLUSIONS:
Multilevel SPOs are feasible for restoration of LL as well as sagittal and
coronal alignment in the ASD population with or without prior instrumented
fusion.
PMID- 28502880
TI - Maternal care modulates the febrile response to lipopolysaccharide through
differences in glucocorticoid receptor sensitivity in the rat.
AB - Early life adversity increases the risk for later infection. The febrile response
is a potent mechanism to combat infection. We found that variations in maternal
care influence the febrile response to 50ug/kg lipopolysaccharide (LPS) challenge
in adult male rats. Offspring from low-licking/grooming (LG) mothers had an
increased febrile response compared to offspring from high-LG mothers challenged
with LPS. Low-LG offspring had reduced plasma IL-6 at one and two hours post
challenge compared to high-LG offspring. IL-6 gene expression in the anterior
hypothalamus was induced following LPS challenge in low-LG offspring but not in
high-LG offspring at two hours post challenge. Occupancy of the transcription
factor nuclear factor kappa-light-chain-enhancer of activated B cells (NFkappaB)
to the IL-6 promoter region in the anterior hypothalamus was greater in low-LG
offspring treated with LPS than in high-LG offspring. These findings suggest
greater activation of thermoregulatory neurons in the anterior hypothalamus of
low-LG compared to high-LG offspring following LPS challenge. Low-LG offspring
had greater plasma corticosterone levels following LPS challenge and they had
enhanced glucocorticoid receptors (GR) in the spleen compared to high-LG
offspring. Enhanced glucocorticoids and glucocorticoid receptor sensitivity
associated with reduced IL-6 induction early post challenge in low-LG offspring.
Challenge with RU-486 prior to LPS challenge eliminated differences in the
febrile response between offspring of high and low-LG mothers. Individual
differences in GR sensitivity may modulate differences in the febrile response to
LPS challenge, exerting a long-term influence on the capacity to recover from
infection.
PMID- 28502882
TI - Single-incision endoscopic thyroidectomy for papillary thyroid cancer: A pilot
study.
AB - BACKGROUND: Recently, we have reported single incision endoscopic thyroidectomy
using an axillary approach with gas inflation (SIET) in cases with benign thyroid
tumors to reduce post-operative pain and invasiveness of the conventional
endoscopic thyroidectomy. The aim of this study was to present our experiences
with SIET for papillary thyroid cancer (PTC). METHODS: Patients who were
diagnosed with histologically papillary thyroid carcinoma (<=1 cm) with single,
unilateral, and intra-thyroidal lesion and without clinical lymph node metastasis
were included. We analyzed clinico-pathological characteristics, surgical
outcomes, and oncologic adequacy of the SIET procedure. RESULTS: Between January
2011 and July 2012, a total of 75 patients underwent hemi-thyroidectomy with
ipsilateral central lymph node dissection via SIET. The mean tumor size was 0.5
cm and 4.1 +/- 2.43 central lymph nodes were removed. Of the patients, 98.3% were
satisfied with their surgical wound post-operatively and no critical post
operative complications occurred during the study, except for one case of post
operative bleeding. There was one case of disease recurrence, which occurred in
the contra-lateral cervical lymph node region 6 months after SIET. This patient
underwent completion thyroidectomy with selective neck dissection. CONCLUSION:
The SIET is a safe and acceptable procedure for PTC with a reduced dissection
field, less post-operative pain, and more cosmetic satisfaction than conventional
endoscopic thyroid surgery.
PMID- 28502883
TI - Comparative evaluation of colonoscopy-assisted transanal minimally invasive
surgery via glove port and endoscopic submucosal dissection for early rectal
tumor.
AB - BACKGROUND: Early rectal tumor is usually managed by local excision. A novel
method-colonoscopy-assisted transanal minimally invasive surgery via glove port
(CA-TAMIS-GP)-for resecting early rectal tumor was developed and compared with
endoscopic submucosal dissection (ESD). MATERIALS AND METHODS: We performed CA
TAMIS-GP surgery on 26 patients from January 2014 to February 2016. For better
analysis, we retrospectively collected data from 31 patients who underwent ESD
between October 2012 and December 2013; overall, 57 patients diagnosed with early
rectal tumor were included in this study. Perioperative conditions and long-term
outcomes of both groups were compared. RESULTS: All lesions were dissected
completely and successfully without conversion to open surgery or major
complications. On histopathologic examination, all specimens in this study had
negative margins. All patients had uneventful postoperative recoveries, except 3
patients of CA-TAMIS-GP with minor hematochezia, which resolved spontaneously; 7
ESD patients had late-onset bleeding and 3 needed colonoscopic hemostasis; 2
patients in each group had mild fever. The CA-TAMIS-GP group had a shorter
operation time, less hemorrhage, and a lower average consumable cost than the ESD
group (P < 0.05); moreover, the CA-TAMIS-GP group had no recurrence or long-term
complications during a follow-up of 10-32 months, whereas3 patients in the ESD
group developed local recurrence during a follow-up of 24-36 months. CONCLUSIONS:
The CA-TAMIS-GP is a new method that is safe and effective in patients with early
rectal tumor and appears to have a shorter operation time and less blood loss as
compared with ESD.
PMID- 28502884
TI - Quantifying sex, race, and age specific differences in bone microstructure
requires measurement of anatomically equivalent regions.
AB - INTRODUCTION: Individuals differ in forearm length. As microstructure differs
along the radius, we hypothesized that errors may occur when sexual and racial
dimorphisms are quantified at a fixed distance from the radio-carpal joint.
METHODS: Microstructure was quantified ex vivo in 18 cadaveric radii using high
resolution peripheral quantitative computed tomography and in vivo in 158 Asian
and Caucasian women and men at a fixed region of interest (ROI), a corrected ROI
positioned at 4.5-6% of forearm length and using the fixed ROI adjusted for cross
sectional area (CSA), forearm length or height. Secular effects of age were
assessed by comparing 38 younger and 33 older women. RESULTS: Ex vivo, similar
amounts of bone mass fashioned adjacent cross sections. Larger distal cross
sections had thinner porous cortices of lower matrix mineral density (MMD), a
larger medullary CSA and higher trabecular density. Smaller proximal cross
sections had thicker less porous cortices of higher MMD, a small medullary canal
with little trabecular bone. Taller persons had more distally positioned fixed
ROIs which moved proximally when corrected. Shorter persons had more proximally
positioned fixed ROIs which moved distally when corrected, so dimorphisms
lessened. In the corrected ROIs, in Caucasians, women had 0.6 SD higher porosity
and 0.6 SD lower trabecular density than men (p<0.01). In Asians, women had 0.25
SD higher porosity (NS) and 0.5 SD lower trabecular density than men (p<0.05). In
women, Asians had 0.8 SD lower porosity and 0.3 SD higher trabecular density than
Caucasians (p<0.01). In men, Asians and Caucasians had similar porosity and
trabecular density. Results were similar using an adjusted fixed ROI. Adjusting
for secular effects of age on forearm length resulted in the age-related
increment in porosity increasing from 2.08 SD to 2.48 SD (p<0.05). CONCLUSION:
Assessment of sex, race and age related differences in microstructure requires
measurement of anatomically equivalent regions.
PMID- 28502885
TI - Contra-lateral bone loss at the distal radius in postmenopausal women after a
distal radius fracture: A two-year follow-up HRpQCT study.
AB - Opposite to the fracture side, bone mineral density (BMD) measured by DXA at the
contra-lateral side does not change after a distal radius fracture. However, it
is unknown if also bone micro-architecture and strength at the contralateral side
are unaffected. Therefore, the aim of this study was to assess BMD, micro
architecture and bone mechanical properties at the contra-lateral side during two
years follow-up after a distal radius fracture using high resolution peripheral
quantitative computed tomography (HRpQCT). The contra-lateral distal radius of 15
postmenopausal women (mean age 64+/-8years) with a distal radius fracture treated
by cast immobilization was scanned by HRpQCT at baseline, 3months and 2years post
fracture. BMD and cortical and trabecular micro-architecture were measured and
biomechanical parameters were estimated using micro finite element analysis
(MUFEA). Additionally, markers of bone resorption and formation were measured at
each visit. Bone parameters and turnover markers across the three visits were
analysed using a linear mixed-effect model with Bonferroni correction. Two years
post-fracture, a significant decrease from baseline was found in cortical BMD (
4.2%, p<0.001), failure load (-6.1%, p=0.001), stiffness in compression (-5.7%,
p=0.003) and bending (-6.4%, p=0.008), and bone formation (-47.6%, p=0.010). No
significant changes from baseline were observed in total and trabecular BMD, nor
in cortical or trabecular micro-architecture and neither in bone resorption.
Results were similar between patients with or without adequate anti-osteoporosis
drug treatment. We found a significant decline in BMD in the cortical but not the
trabecular region, and a reduction in bone strength and stiffness at the contra
lateral side two years after a distal radius fracture. These changes exceeded the
changes that may be expected due to aging, even in the presence of adequate anti
osteoporosis treatment.
PMID- 28502886
TI - HMGA2, a driver of inflammation, is associated with hypermethylation in acute
liver injury.
AB - Acute liver injury (ALI) is characteristic of abrupt hepatic dysfunction and
inflammatory response. Activaion of Kupffer cells (KCs) plays a central role in
the pathogenesis of ALI. Since the High Mobility Group A protein2 (HMGA2) occurs
as a driver at critical stage of hepatocellular carcinoma, herein, we
investigated the role of HMGA2 in macrophage activation during ALI. Our study
found that the expression of HMGA2 decreased dramatically both in KCs isolated
from the liver in mice with ALI and in LPS-induced RAW264.7 cell lines. Moreover,
loss- and gain-of-function studies suggested that HMGA2 could enhance the
expression of pro-inflammatory cytokines including TNF-alpha, IL-6 and IL-1beta.
These results indicated that HMGA2 may play an essential role in macrophage
activation during ALI. Additionally, our results showed the expression of HMGA2
was up-regulated when LPS-induced RAW264.7 cells were treated with 5-aza-2
deoxycytidine. Furthermore, silencing of DNMT1, DNMT3a, DNMT3b could respectively
prevent the down-expression of HMGA2 in LPS-induced RAW264.7 cells. In
conclusion, HMGA2 promotes the release of pro-inflammatory cytokines through NF
kappaB pathway, and the dysregulation of HMGA2 may involve with hypermethylation.
PMID- 28502887
TI - Open Surgical Treatment of Secondary Aortoesophageal and Aortobronchial Fistula
after Thoracic Endovascular Aortic Repair and Esophagocoloplasty in a Second
Procedure.
AB - Aortoesophageal (AEF) and aortobronchial fistula (ABF) after thoracic
endovascular aortic repair (TEVAR) are rare complications with catastrophic
consequences without treatment. In this case report, we presented a patient with
AEF and ABF after TEVAR successfully treated with endograft explantation and
replaced by Dacron graft followed by esophagectomy and left principal bronchus
repairing. We report a patient with AEF and ABF after TEVAR who was evaluated due
to dysphagia and chest pain followed by hematemesis and hemoptysis. Endoscopic
examination revealed lesion of the esophageal wall with chronic abscess formation
and stent-graft protrusion into the cavity. Patient was operated on with
extracorporeal circulation. AEF and ABF were confirmed intraoperatively.
Endograft was explanted and in situ reconstruction of thoracic aorta was carried
out with tubular Dacron 22-mm prosthesis wrapped with omental flap. After aortic
reconstruction, esophageal mucosal stripping was performed with cervical
esophagostomy, pyloromyotomy, and Stamm-Kader gastrostomy for nutrition. In
addition, omentoplasty of the defect in the left principal bronchus was
performed. To re-establish peroral food intake esophagocoloplasty was carried out
8 months after previous surgery utilizing transversosplenic segment of the colon
and retrosternal route. In very selective cases, stent-graft explantation and in
situ reconstruction with Dacron graft covered by omental flap followed by
esophagectomy and bronchus repairing permit adequate debridement reducing the
risk of mediastinitis and graft infection and allow a safe esophageal
reconstruction in a second procedure.
PMID- 28502888
TI - Prospective Study of Postoperative Glycemic Control with a Standardized Insulin
Infusion Protocol after Infrainguinal Bypass and Open Abdominal Aortic Aneurysm
Repair.
AB - BACKGROUND: The aim of this study is to examine the effect of moderate
postoperative glycemic control in diabetic and nondiabetic patients undergoing
infrainguinal bypass (INFRA) or open abdominal aortic aneurysm (OAAA) repair.
METHODS: In a single center prospective study, we investigated postoperative
glycemic control using a standardized insulin infusion protocol after elective
INFRA bypass (n = 53, 62%) and OAAA repair (n = 33, 38%) between January 2013 and
March 2015. The primary end point was optimal glycemic control, defined as having
>=85% of blood glucose values within the 80-150 mg/dL target range. Suboptimal
glycemic control was defined as <85% of blood glucose values within the blood
glucose target range. Secondary end points included in-hospital and 30-day
surgical site infection (SSI) rates, composite adverse events, length of stay
(LOS), and hospital cost. RESULTS: Optimal glycemic control was achieved more
commonly after OAAA repair than INFRA bypass (85% vs. 64%, P = 0.04). Moderate
hypoglycemia (<70 mg/dL) was observed in 32 (37%) patients, while severe
hypoglycemia (<50 mg/dL) was observed in 6 (7%) patients. SSI at 30 days was more
common after INFRA bypass (n = 15, 29%) than OAAA repair (n = 2, 6%) (P = 0.01).
In-hospital (6% vs. 6%, P = 1.0) and 30-day (24% vs. 22%, P = 1.0) SSI rates were
similar for optimal versus suboptimal glycemic control patients after INFRA
bypass. In-hospital (4% vs. 0%, P = 1.0) and 30-day (4% vs. 0%, P = 1.0) SSI
rates were similar for optimal versus suboptimal glycemic control patients after
OAAA repair. The percentage of blood glucose > 250 mg/dL was similar for patients
with and without SSI (3% vs. 2%, P = 0.36). Adverse cardiac and pulmonary events
after INFRA bypass were similar between groups (9% vs. 21%, P = 0.23; 0% vs. 5%,
P = 0.36, respectively). Adverse cardiac and pulmonary events after OAAA repair
were similar between groups (2% vs. 0%, P = 1.0; 4% vs. 0%, P = 1.0,
respectively). Mean LOS was significantly lower in patients with optimal glycemic
control after INFRA bypass (4.2 vs. 7.3 days, P = 0.02). Mean LOS was similar
after OAAA repair for patients with optimal and suboptimal control (5.8 vs. 6.4
days, P = 0.46). Inpatient hospital costs after INFRA bypass were lower for the
group with optimal (median $25,012, interquartile range [IQ] range $21,726
28,331) versus suboptimal glycemic control (median $28,944, IQ range 24,773
41,270, P = 0.02). CONCLUSIONS: Postoperative hyperglycemia is common after INFRA
bypass and OAAA repair and can be effectively ameliorated with an insulin
infusion protocol. The protocol was low risk with reduced LOS and cost after
INFRA bypass. Complications including SSI were not reduced in patients with
optimal perioperative glycemic control.
PMID- 28502889
TI - Three-Dimensional Printing Facilitates Successful Endovascular Closure of a Type
II Abernethy Malformation Using an Amplatzer Atrial Septal Occluder Device.
AB - Type II Abernethy malformations, characterized by side-to-side portosystemic
shunting with preserved intrahepatic portal venous system, have been treated with
shunt closure surgically and endovascularly. Three-dimensional printing has been
used to develop highly accurate patient-specific representations for surgical and
endovascular planning and intervention. This innovation describes 3-dimensional
printing to successfully close a flush-oriented type II Abernethy malformation
with discrepant dimensions on computed tomography, conventional venography, and
intravascular ultrasound, using a 12-mm Amplatzer atrial septal occluder device.
PMID- 28502890
TI - A quantitative approach to understanding vertebrate limb morphogenesis at the
macroscopic tissue level.
AB - To understand organ morphogenetic mechanisms, it is essential to clarify how
spatiotemporally-regulated molecular/cellular dynamics causes physical tissue
deformation. In the case of vertebrate limb development, while some of the genes
and oriented cell behaviors underlying morphogenesis have been revealed, tissue
deformation dynamics remains incompletely understood. We here introduce our
recent work on the reconstruction of tissue deformation dynamics in chick limb
development from cell lineage tracing data. This analysis has revealed globally
aligned anisotropic tissue deformation along the proximo-distal axis not only in
the distal region but also in the whole limb bud. This result points to a need,
as a future challenge, to find oriented molecular/cellular behaviors for
realizing the observed anisotropic tissue deformation in both proximal and distal
regions, which will lead to systems understanding of limb morphogenesis.
PMID- 28502891
TI - Regulated transport of signaling proteins from synapse to nucleus.
AB - Synapse-to-nucleus communication is essential for neural development, plasticity,
and repair. In addition to fast electrochemical signaling, neurons employ a
slower mechanism of protein transport from synapse-to-nucleus. This mechanism
provides potential advantages, including the encoding of spatial information.
Many synaptonuclear signaling proteins are transported from the postsynaptic
compartment to the nucleus in an activity-dependent manner. The phosphorylation
state of two such proteins, CRTC1 and Jacob, is dependent on the stimulus type.
While most studies have focused on postsynaptic synaptonuclear communication, a
transcriptional co-repressor, CtBP1, was recently discovered to undergo activity
dependent translocation from the presynaptic compartment to the nucleus. Recent
evidence indicates that synapse-to-nucleus communication could be cell type
specific, including the identification of a distinct mechanism of excitation
transcription coupling in inhibitory neurons.
PMID- 28502892
TI - Biomarkers kinetics in the assessment of ventilator-associated pneumonia response
to antibiotics - results from the BioVAP study.
AB - PURPOSE: Our aim was to evaluate the role of biomarker kinetics in the assessment
of ventilator-associated pneumonia (VAP) response to antibiotics. MATERIALS AND
METHODS: We performed a prospective, multicenter, observational study to evaluate
in 37 microbiologically documented VAP, the kinetics of C-reactive protein (CRP),
procalcitonin (PCT), mid-region fragment of pro-adrenomedullin (MR-proADM). The
kinetics of each variable, from day 1 to 6 of therapy, was assessed with a time
dependent analysis comparing survivors and non-survivors. RESULTS: During the
study period kinetics of CRP as well as its relative changes, CRP-ratio, was
significantly different between survivors and non-survivors (p=0.026 and p=0.005,
respectively). On day 4 of antibiotic therapy, CRP of survivors was 47% of the
initial value while it was 96% in non-survivors. The kinetics of other studied
variables did not distinguish between survivors and non-survivors. In survivors
the bacterial load also decreased markedly. Adequate initial antibiotic therapy
was associated with lower mortality (p=0.025) and faster CRP decrease (p=0.029).
CONCLUSIONS: C-reactive protein kinetics can be used to identify VAP patients
with poor outcome as soon as four days after the initiation of treatment. (Trial
registration - NCT02078999; registered 3 August 2012).
PMID- 28502893
TI - The effect of exhalation flow on endogenous particle emission and phospholipid
composition.
AB - Exhaled particles constitute a micro-sample of respiratory tract lining fluid.
Inhalations from low lung volumes generate particles in small airways by the
airway re-opening mechanism. Forced exhalations are assumed to generate particles
in central airways by mechanisms associated with high air velocities. To increase
knowledge on how and where particles are formed, different breathing manoeuvres
were compared in 11 healthy volunteers. Particles in the 0.41-4.55MUm diameter
range were characterised and sampled. The surfactant lipid
dipalmitoylphosphatidylcholine (DPPC) was quantified by mass spectrometry. The
mass of exhaled particles increased by 150% (95% CI 10-470) for the forced
exhalation and by 470% (95% CI 150-1190) for the airway re-opening manoeuvre,
compared to slow exhalations. DPPC weight percent concentration (wt%) in
particles was 2.8wt% (95%CI 1.4-4.2) and 9.4wt% (95%CI 8.0-10.8) for the forced
and the airway re-opening manoeuvres, respectively. In conclusion, forced
exhalation and airway re-opening manoeuvres generate particles from different
airway regions having different DPPC concentration.
PMID- 28502894
TI - Soluble 1:1 complexes and insoluble 3:2 complexes - Understanding the phase
solubility diagram of hydrocortisone and gamma-cyclodextrin.
AB - The molecular mechanisms underlying the drug-solubilizing properties of gamma
cyclodextrin were explored using hydrocortisone as a model drug. The BS-type
phase-solubility diagram of hydrocortisone with gamma-cyclodextrin was thoroughly
characterized by measuring the concentrations of hydrocortisone and gamma
cyclodextrin in solution and the solid phase. The drug-solubilizer interaction
was also studied by isothermal titration calorimetry from which a precise value
of the 1:1 binding constant (K11=4.01mM-1 at 20 degrees C) was obtained. The
formation of water-soluble 1:1 complexes is responsible for the initial increase
in hydrocortisone solubility while the precipitation of entities with a 3:2 ratio
of gamma-cyclodextrin:hydrocortisone is responsible for the plateau and the
ensuing strong decrease in solubility once all solid hydrocortisone is used up.
The complete phase-solubility diagram is well accounted for by a model employing
the 1:1 binding constant and the solubility product of the precipitating 3:2
entity (K32S=5.51 mM5). For such systems, a small surplus of gamma-cyclodextrin
above the optimum concentration may result in a significant decrease in drug
solubility, and the implications for drug formulations are briefly discussed.
PMID- 28502896
TI - A quality by design (QbD) twin-Screw extrusion wet granulation approach for
processing water insoluble drugs.
AB - In this study, a Quality by Design (QbD) approach was used to identify the effect
of formulation parameters in a twin screw wet extrusion granulation process for
the manufacturing of ibuprofen (IBU) granules with increased dissolution rates. A
fractional factorial Design of Experiment (DoE) was used to investigate the
effect of the excipient composition, binder amount and liquid to solid (L/S)
ratio (independent variables) on drug dissolution rates, median particle size
diameter and specific surface area (dependent variables). The intra-granular
addition of the binder in inorganic/polymer blends processed with ethanol as
granulating liquids facilitated the formation of granules at various particle
sizes. DoE regression analysis showed that all formulation parameters affect the
dependent variables significantly. The enhanced dissolution rates were attributed
not only to the IBU particle size reduction and adsorption in the porous
inorganic network but also to the high specific surface area of the produced
granules. Dynamic vapour sorption showed increased water absorption for granules
with small particle size distribution and high specific surface area.
PMID- 28502895
TI - Nanostructured lipid carriers employing polyphenols as promising anticancer
agents: Quality by design (QbD) approach.
AB - Cancer is one of the leading causes of death worldwide. There are several hurdles
in cancer therapy because of side-effects which limits its usage. Nanoparticulate
drug delivery systems have been tested against cancer in a range of scientific
studies. In the recent years, advanced research on Nanostructured Lipid Carriers
(NLCs) has garnered considerable attention owing to the advantages over their
first-generation counterparts, Solid Lipid Nanoparticles (SLN). NLCs facilitate
efficient loading of poorly water soluble drugs with simple methods of drug
loading. Recently, there is an increased interest in polyphenols because of the
evidence of their promising role in prevention of cancer. Polyphenols are
produced as secondary metabolites by plants. Their role in prevention of
development of tumors through variety of mechanisms and reduction of tumor cell
mass has been reported. This article aims to review the science behind
development of NLCs and role of polyphenols as promising anticancer agents.
Principles of Quality by Design (QbD) have also been explained which are used in
formulation-development of many nanoparticles, including NLCs, as reported in
literature.
PMID- 28502897
TI - A multifunctional beta-cyclodextrin-conjugate photodelivering nitric oxide with
fluorescence reporting.
AB - This contribution reports the design, synthesis and photochemical properties of a
novel cationic, water soluble, beta-cyclodextrin (betaCD) conjugate integrating
an anthracene moiety and a nitroaniline derivative within the primary side of the
betaCD scaffold. Photoinduced energy transfer between the anthracene and the
nitroaniline chromophores effectively suppresses the fluorescence of the
anthracene unit. Excitation with visible light triggers the release of nitric
oxide (NO) from the nitroaniline chromophore, accompanied to the concomitant
revival of the anthracene fluorescence, which acts as an optical reporter for
detecting the amount of the NO released. Furthermore, the anthracene moiety
photogenerates singlet oxygen (1O2) sequentially to NO release. The conjugate is
also able to accommodate hydrophobic guests within the betaCD cavity, as proven
by using naphthalene as a model compound. In view of the key role NO and 1O2 play
as anticancer and antibacterial species, the present betaCD derivative represents
an intriguing candidate for further studies in biopharmaceutical research
addressed to multimodal therapeutic applications.
PMID- 28502898
TI - Development of modified release 3D printed tablets (printlets) with
pharmaceutical excipients using additive manufacturing.
AB - The aim of this study was to manufacture 3D printed tablets (printlets) from
enteric polymers by single filament fused deposition modeling (FDM) 3D printing
(3DP). Hot melt extrusion was used to generate paracetamol-loaded filaments from
three different grades of the pharmaceutical excipient hypromellose acetate
succinate (HPMCAS), grades LG, MG and HG. One-step 3DP was used to process these
filaments into enteric printlets incorporating up to 50% drug loading with two
different infill percentages (20 and 100%). X-ray Micro Computed Tomography
(Micro-CT) analysis revealed that printlets with 20% infill had cavities in the
core compared to 100% infill, and that the density of the 50% drug loading
printlets was higher than the equivalent formulations loaded with 5% drug. In
biorelevant bicarbonate dissolution media, drug release from the printlets was
dependent on the polymer composition, drug loading and the internal structure of
the formulations. All HPMCAS-based printlets showed delayed drug release
properties, and in the intestinal conditions, drug release was faster from the
printlets prepared with polymers with a lower pH-threshold: HPMCAS LG > HPMCAS MG
> HPMCAS HG. These results confirm that FDM 3D printing makes it possible not
only to manufacture delayed release printlets without the need for an outer
enteric coating, but it is also feasible to adapt the release profile in response
to the personal characteristics of the patient, realizing the full potential of
additive manufacturing in the development of personalised dose medicines.
PMID- 28502899
TI - The expression of P450 genes mediating fenpropathrin resistance is regulated by
CncC and Maf in Tetranychus cinnabarinus (Boisduval).
AB - Although overexpression of genes encoding detoxification enzymes is a well-known
mechanism of pesticide resistance of mites, the regulators involved in this
process are still illiterate. Previous studies in our laboratory demonstrated
that the overexpression of six P450 genes contributes to fenpropathrin resistance
in T. cinnabarinus. In this study, six transcription factor genes that likely
regulate the expression of P450 genes were identified and characterized.
Quantitative PCR (qPCR) analysis showed that three transcription factor genes
were highly expressed in a fenpropathrin-resistant (FeR) strain of T.
cinnabarinus. The cap 'n' collar isoform C (CncC) and muscle aponeurosis
fibromatosis (Maf) family transcription factors were identified as the key
regulator of P450 genes by RNA interference (RNAi). Furthermore, research on the
promoters of these P450 genes using reporter assays identified that CncC and Maf
influence the susceptibility of T. cinnabarinus to fenpropathrin through
regulating the expression of P450 genes. This study increases our understanding
of the molecular mechanisms underlying the regulation of P450 genes involved in
detoxification of acaricides in T. cinnabarinus.
PMID- 28502900
TI - Nuclear morphometry in histological specimens of canine prostate cancer:
Correlation with histological subtypes, Gleason score, methods of collection and
survival time.
AB - Ten normal prostates, 22 benign prostatic hyperplasia (BPH) and 29 prostate
cancer (PC) were morphometrically analyzed with regard to mean nuclear area
(MNA), mean nuclear perimeter (MNP), mean nuclear diameter (MND), coefficient of
variation of the nuclear area (NACV), mean nuclear diameter maximum (MDx), mean
nuclear diameter minimum (MDm), mean nuclear form ellipse (MNFe) and form factor
(FF). The relationship between nuclear morphometric parameters and histological
type, Gleason score, methods of sample collection, presence of metastases and
survival time of canine PC were also investigated. Overall, nuclei from
neoplastic cells were larger, with greater variation in nuclear size and shape
compared to normal and hyperplastic cells. Significant differences were found
between more (small acinar/ductal) and less (cribriform, solid) differentiated
PCs with regard to FF (p<0.05). MNA, MNP, MND, MDx, and MDm were significantly
correlated with the Gleason score of PC (p<0.05). MNA, MNP, MDx and MNFe may also
have important prognostic implications in canine prostatic cancer since
negatively correlated with the survival time. Biopsy specimens contained nuclei
that were smaller and more irregular in comparison to those in prostatectomy and
necropsy specimens and therefore factors associated with tissue sampling and
processing may influence the overall morphometric evaluation. The results
indicate that nuclear morphometric analysis in combination with Gleason score can
help in canine prostate cancer grading, thus contributing to the establishment of
a more precise prognosis and patient's management.
PMID- 28502902
TI - Retinoic acid-mediated anti-inflammatory responses in equine immune cells
stimulated by LPS and allogeneic mesenchymal stem cells.
AB - Retinoic acid (RA), an active metabolite of vitamin A, has shown potential
therapeutic immunomodulatory properties. Allogeneic mesenchymal stem cells (MSCs)
based therapy is an effective approach to induce tissue healing and regeneration
in many equine orthopedic conditions. However, MSCs-based therapies induced
inflammatory responses in vivo. This study aimed to: 1. Determine the effect of
RA cell culture treatment on inflammatory responses of lipopolysaccharides (LPS)-
and allogeneic MSCs-stimulated peripheral blood mononuclear cells (PBMCs). 2.
Determine the effect of RA on stimulated MSCs viability and morphology.
Allogeneic MSCs-stimulated PBMCs had significant decreases in the anti
inflammatory cytokines (IL-10, IL-1ra, TGF-beta1), increases in the pro
inflammatory mediators (IL-1beta, IL-6, TNF-alpha, SAA), and increases of CD14
and MHC II percent positive cells compared to LPS- and non-stimulated PBMCs.
Retinoic acid treatment of LPS- and allogeneic MSCs-stimulated PBMCs
counterbalanced the induced inflammatory responses. Moreover, RA significantly
improved the viability and morphology of stimulated MSCs. These findings
highlighted the potential complications of equine allogeneic MSCs-based therapies
and the immuno-modulatory effect of RA on equine stimulated cells. In conclusion,
the use of RA to ameliorate allogeneic MSCs therapy associated inflammation may
offer advantages that would require further investigations.
PMID- 28502901
TI - Neuraminidase activity of blue eye disease porcine rubulavirus: Specificity,
affinity and inhibition studies.
AB - Porcine rubulavirus (PorPV), also known as La Piedad Michoacan Virus (LPMV)
causes encephalitis and reproductive failure in newborn and adult pigs,
respectively. The hemagglutinin-neuraminidase (HN) glycoprotein is the most
exposed and antigenic of the virus proteins. HN plays central roles in PorPV
infection; i.e., it recognizes sialic acid-containing cell receptors that mediate
virus attachment and penetration; in addition, its neuraminidase (sialic acid
releasing) activity has been proposed as a virulence factor. This work describes
the purification and characterization of PorPV HN protein (isolate PAC1). The
specificity of neuraminidase is restricted to sialyl(alpha2,3)lactose (3SL). HN
showed typical Michaelis-Menten kinetics with fetuin as substrate (km=0.029MUM,
Vmax=522.8nmolmin-1mg-1). When 3SL was used as substrate, typical cooperative
kinetics were found (S50=0.15MUM, Vmax=154.3nmolmin-1mg-1). The influenza
inhibitor zanamivir inhibited the PorPV neuraminidase with IC50 of 0.24MUM. PorPV
neuraminidase was activated by Ca2+ and inhibited by nucleoside triphosphates
with the level of inhibition depending on phosphorylation level. The present
results open possibilities to study the role of neuraminidase in the
pathogenicity of PorPV infection and its potential inhibitors.
PMID- 28502903
TI - Subclinical bovine vaccinia: An important risk factor in the epidemiology of this
zoonosis in cattle.
AB - Bovine vaccinia (BV) is a zoonosis caused by Vaccinia virus (VACV) that mainly
affects lactating cows and dairy farm milkers. The epidemiological role(s) of
other cattle categories such as dry cows, bulls, and heifers in BV remains
unclear. This study was performed to investigate VACV in affected dairy cattle
herds and perifocal farms during an outbreak in Brazil. Crusts from lesions of
cows' teats were collected from all farms with BV outbreaks. Milk, feces, blood,
and serum were collected from symptomatic and asymptomatic lactating cows. Blood
and serum were also sampled from other cattle categories (calves, heifers, dry
cows, and bulls). The samples were tested for VACV by PCR, and to confirm VACV
viability, VACV-positive samples were inoculated in BSC-40 cells and stained
using immunoperoxidase. Neutralizing antibodies were investigated using plaque
reduction neutralization test. Viral DNA was detected in milk, blood, and feces
samples of symptomatic and asymptomatic dairy cows and in blood samples from
other cattle categories on farms with and without confirmed BV outbreak. In
affected farms, viable virus was identified in feces and milk samples from
lactating cows and in blood samples from asymptomatic dry cows. Viable VACV was
also identified in feces from lactating cows and one bull's blood sample from
perifocal farms. Neutralizing antibodies were detected in 81.6% of the herds
affected by BV and in 53.8% of the herds on perifocal farms. The presented data
indicate a potential source of viral dissemination, which contributes to the
persistence and spread of VACV in the environment.
PMID- 28502904
TI - Src and Syk contribute to the anti-inflammatory activities of Achyranthes aspera
ethanolic extract.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Nuclear factor-kappa B (NF-kappaB) plays pivotal
roles in inflammation. Src and Syk are two tyrosine kinases that act upstream of
NF-kappaB signaling. Although Achyranthes aspera L. (A. aspera) has been used as
a traditional medicine to treat fevers and inflammatory ailments and heal wounds,
the molecular mechanisms of its anti-inflammatory actions are not yet fully
understood. MATERIALS AND METHODS: In this study, we evaluated the anti
inflammatory effect of A. aspera ethanol extract (Aa-EE). To determine the
mechanism by which Aa-EE dampens the inflammatory response, nitric oxide (NO)
production and the mRNA expression levels of tumor necrosis factor (TNF)-alpha
and inducible nitric oxide synthase (iNOS) were examined by Griess assay and RT
PCR. Luciferase assays and immunoblotting were also conducted to examine how Aa
EE regulates the NF-kappaB pathway. RESULTS: Aa-EE reduced NO production up to
60% without any cytotoxicity. This extract was found to downregulate the mRNA
expression levels of inflammatory genes. Aa-EE blocked NF-kappaB promoter
activity induced by both TNF-alpha and adaptor molecule MyD88 (about 70% and 40%,
respectively). Moreover, nuclear translocation of p65 and IkappaBalpha
phosphorylation were also inhibited. Furthermore, Aa-EE inactivated two upstream
signaling molecules, the Src and Syk kinases. In accordance with these data, the
kinase activities of Src and Syk were decreased by 50% and 80%, respectively. The
anti-inflammatory action of Aa-EE was also confirmed in a gastritis model.
CONCLUSION: Our data suggest that Aa-EE targets NF-kappaB to exert its anti
inflammatory properties by suppressing Src and Syk. Therefore, our study raises
the possibility that this extract can be developed as a novel natural anti
inflammatory remedy.
PMID- 28502905
TI - Inhibition of proinflammatory mediators by coumaroyl lupendioic acid, a new
lupane-type triterpene from Careya arborea, on inflammation-induced animal model.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Careya arborea Roxb. (Lecythidaceae) is a large
tree found throughout India in deciduous forests and grasslands. C. arborea is
traditionally used in tumors, inflammation, anthelmintic, bronchitis, epileptic
fits, astringents, antidote to snake-venom, skin disease, diarrhea, dysentery
with bloody stools, dyspepsia, ulcer, tooth ache, and ear pain. AIM OF THE STUDY:
In our previous work, the methanolic extract of Careya arborea stem bark showed
significant anti-inflammatory activity. As a continuity of that work, this study
aimed at the isolation and evaluation of the anti-inflammatory effect of
coumaroyl lupendioic acid, a new lupane-type triterpene from Careya arborea stem
bark. Further, to give an insight into the underlying mechanism of action of the
compound on the modulation of proinflammatory mediators. MATERIALS AND METHODS:
Methanolic extract of Careya arborea stem bark was suspended in water, and
sequentially fractionated with n-hexane and ethyl acetate. Further ethyl acetate
fraction was subjected to medium pressure liquid chromatography (MPLC) to isolate
the active molecules. The isolated compounds were characterized by the various
spectral techniques namely UV, IR, 1H NMR, 13C NMR, DEPT, 1H-1H COSY, HMBC and
Mass spectral techniques. In vitro COX-1 and COX-2 enzyme inhibition assays using
human whole blood was performed to investigate the inhibitory effect of the
isolated compounds. The resulted potent COX-2 inhibitor of the isolated
constituents compound 5, designated as coumaroyl lupendioic acid (CLA), was
investigated in carrageenan induced inflammation and its effect was also compared
with betulinic acid (BA) at the doses of 10 and 20mgkg-1, p.o. using indomethacin
and celecoxib (10 and 20mgkg-1, p.o., respectively) as reference drugs. The
effect of CLA on the production of NO, MPO, PGE2, TNF-alpha, IL-1beta and IL-6
were assessed. In addition, the histopathology and immunohistochemistry (NF-?B,
COX-2 and TNF-alpha protein expression) in paw tissues were also carried out.
RESULTS: The chromatographic fractionation of the methanolic extract resulted in
isolation of six new derivatives of lupane type triterpenes for the first time
from the stem bark of C. arborea; 3beta-hydroxy-lup-5,20 (29),21-trien-28-oic
acid (Compound 1), 1, 3, 13, 16-tetrahydroxy-lup-9(11), 20(29)-diene-28-oic acid
(Compound 2), 1, 7-di hydroxy betulinic acid (Compound 3), 3beta-O
dihydrocinnamyl betulinic acid (Compound 4), 3beta-O-trans-coumaryl-lup-6, 9(11),
20(29)-triene-27, 28-dioic acid (Compound 5), 16beta-hydroxy-2, 3-seco-lup-5,
20(29)-dien-2, 3, 28-trioic acid (Compound 6). Among the all isolated compounds
3beta-O-trans-coumaryl-lup-6, 9(11), 20(29)-triene-27, 28-olioic acid designated
as coumaroyl lupendioic acid (CLA) showed higher COX-2 selectivity which is
comparable to reference drug (celecoxib). CLA significantly reduced carrageenan
induced inflammation whereas CLA revealed greater effect as compared to BA at the
similar corresponding doses. Moreover, CLA significantly inhibited pro
inflammatory mediators elevated by carrageenan. CLA also preserved the tissue
architecture as evidenced by the histopathology. Furthermore, immunohistochemical
studies revealed that CLA significantly down regulated NF-?B, COX-2 and TNF-alpha
protein expression. CONCLUSION: The study gives an insight into the molecular
mechanisms of coumaroyl lupendioic acid and suggests that the down-regulations of
proinflammatory mediators provide credence to the ethno botanical use of the
plant in the management of inflammation.
PMID- 28502906
TI - Anti-inflammatory effects of Forsythia suspensa in dextran sulfate sodium-induced
colitis.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Forsythia suspensa Fructus (FS) is used to treat
various inflammatory disorders in traditional Oriental medicine, including
gastrointestinal diseases, but its therapeutic potential in ulcerative colitis is
unclear. Thus, we investigated any potential therapeutic effects of FS against
intestinal inflammation and the bioactive constituents in FS. MATERIALS AND
METHODS: After the induction of colitis using 3% dextran sulfate sodium, FS
(100mg/kg/day) was administered orally during the experimental period. We
evaluated body weight, bloody diarrhea, colon length, and pro-inflammatory
cytokine levels. Subsequently, the bioactive constituents of FS were identified
using UPLC/MS/MS. RESULTS: FS significantly decreased the body weight loss, colon
length shortening, and tumor necrosis factor-alpha and interleukin-6 elevations
induced by colitis compared with the negative control (P < 0.05). Moreover, FS
improved the colitis-induced histopathological damage to the colon, including
epithelial necrosis, infiltration of inflammatory cells, ulceration, and
submucosal edema. In phytochemical analyses, 7 flavonoids, 9 lignans, 13
phenolics, and 2 triterpenes were identified by comparison with the retention
times and mass fragmentations of authentic standards. CONCLUSIONS: We
demonstrated beneficial effects of FS and its constituents, suggesting their
potential for treatment of intestinal inflammation. These data could provide
useful information for managing ulcerative colitis.
PMID- 28502907
TI - Neuropathic and inflammatory antinociceptive effects and electrocortical changes
produced by Salvia divinorum in rats.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Salvia divinorum is a medicinal plant
traditionally used in hallucinogenic ethnopharmacological practices and for its
analgesic and antinflammatory properties. Its active compounds include diterpenes
known as salvinorins which act as potent kappa opioid receptor agonists. AIM OF
THE STUDY: Given its effects in acute animal models of pain, as well as its
antinflammatory attributes, we decided to investigate the analgesic effects of an
SD extract in neuropathic (sciatic loose nerve ligature) and inflammatory (intra
plantar carrageenan) pain models in rats. We also determined in this study the
electrocorticographic changes to correlate similar hallucinogenic state and
behavior as those produced in humans. MATERIAL AND METHODS: Mechanical and
thermonociceptive responses, plantar test and von Frey assay, respectively, were
measured in adult Wistar rats 30min, 3h and 24h after the intraperitoneal
administration of saline or an hydroponic SD extract. We also evaluated
carbamazepine and celecoxib, as gold reference drugs, to compare its
antinociceptive effects. RESULTS: Our results showed that administration of SD
extract induced antialgesic effects in both neuropathic and inflammatory pain
models. All those effects were blocked by nor-binaltorphimine (a Kappa opioid
receptor antagonist). Moreover, it was observed an increase of the anterior power
spectral density and a decrease in the posterior region as electrocorticographic
changes. CONCLUSION: The present investigation give evidence that SD is capable
to reduce algesic response associated to neuropathic and inflammatory
nociception. This study support therapeutic alternatives for a disabling health
problem due to the long term pain with high impact on population and personal and
social implications.
PMID- 28502908
TI - Chronic administration of antioxidant resin from Virola oleifera attenuates
atherogenesis in LDLr -/- mice.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Virola oleifera (Schott) A. C. Smith,
Myristicaceae has been largely used in traditional folk medicine in Brazil as an
anti-inflammatory agent and our previous data indicated the antioxidant
properties in other oxidative stress-related models. However, its effects on
atherosclerosis (AT) are not yet investigated. AIMS OF THE STUDY: To evaluate the
influence of resin from Virola oleifera (RV) on progression of AT in LDLr-/-
mice. MATERIALS AND METHODS: LDLr-/- mice were divided into 4 groups: 1) The ND
group received a normal diet without treatment. 2) The HD group received a high
fat diet without treatment. 3) The HD-V50 received a high-fat diet and was orally
treated with RV at 50mg/Kg. 4) The HD-V300 received a high-fat diet and was
orally treated with RV at 300mg/Kg. After 4 weeks, blood was collected to
quantify biochemical parameters and ROS total and the aorta was removed to
measure the lipid deposition by en face analysis. The liver was also collected to
determine total lipids and lipid and protein oxidation. In order to investigate
in more detail the contributions of RV in the vascular structure, we carried out
the in vitro tests using four cellular types: macrophages, fibroblasts, vascular
smooth muscle and endothelial cells. RESULTS: We showed that the chronic
treatment of RV at both doses reduced vascular lipid accumulation (~50%, p<0.05),
probably through systemic and hepatic antioxidant effects, independent of
dyslipidemia. Moreover, the in vitro assay results demonstrated that RV develops
antioxidant properties on the vascular smooth muscle and endothelial cells,
reinforcing the protective role of RV in progression of AT. LPS-stimulated
macrophages treated with RV resulted in a significant reduction of NO production
in a concentration-dependent manner. CONCLUSIONS: Chronic treatment with RV
diminishes lipid deposition in atherosclerotic mice, which may be justified, at
least in part, by antioxidant systemic and local mechanisms, reinforcing the
protective role this resin in the setting of vascular lipid deposition,
independent of hypercholesterolemia.
PMID- 28502909
TI - Character-level neural network for biomedical named entity recognition.
AB - Biomedical named entity recognition (BNER), which extracts important named
entities such as genes and proteins, is a challenging task in automated systems
that mine knowledge in biomedical texts. The previous state-of-the-art systems
required large amounts of task-specific knowledge in the form of feature
engineering, lexicons and data pre-processing to achieve high performance. In
this paper, we introduce a novel neural network architecture that benefits from
both word- and character-level representations automatically, by using a
combination of bidirectional long short-term memory (LSTM) and conditional random
field (CRF) eliminating the need for most feature engineering tasks. We evaluate
our system on two datasets: JNLPBA corpus and the BioCreAtIvE II Gene Mention
(GM) corpus. We obtained state-of-the-art performance by outperforming the
previous systems. To the best of our knowledge, we are the first to investigate
the combination of deep neural networks, CRF, word embeddings and character-level
representation in recognizing biomedical named entities.
PMID- 28502911
TI - Fake News, Alternative Facts, Post-Truths, Misinformation, Misinterpretation-and
Other Challenges Associated With Knowledge Generation.
PMID- 28502910
TI - Balancing volume and duration of information consumption by physicians: The case
of health information exchange in critical care.
AB - BACKGROUND: The realization of the potential benefits of health information
exchange systems (HIEs) for emergency departments (EDs) depends on the way these
systems are actually used. The attributes of volume of information and duration
of information processing are important for the study of HIE use patterns in the
ED, as cognitive load and time constraints may result in a trade-off between
these attributes. Experts and non-experts often use different problem-solving
strategies, which may be consequential for their system use patterns. Little
previous research focuses on the trade-off between volume and duration of system
use or on the factors that affect it, including user expertise. OBJECTIVES: This
study aims at exploring the trade-off of volume and duration of use, examining
whether this relationship differs between experts and non-experts, and
identifying factors that are associated with use patterns characterized by volume
and duration. METHODS: The research objectives are pursued in the context of
critically-ill patients, treated at a busy ED in the period 2010-2012. The
primary source of internal and external data is an HIE linked to 14 hospitals,
over 1300 clinics, and other clinical facilities. We define four use profiles
based on the attributes of duration and volume: quick and basic, quick and deep,
slow and basic, and slow and deep. The volume and duration of use are computed
using HIE log files as the number of screens and the time per screen,
respectively. Each session is then classified into a specific profile based on
distances from predefined profile centroids. Experts are physicians that are
board-certified in emergency medicine. We test the distribution of use profiles
and their associations with multiple variables that describe the patient,
physician, situation, information available in the HIE system, and use dynamics
within the encounter. RESULTS: The quick and basic profile is the most prevalent.
While available admission summaries are associated with quick and basic use, lab
and imaging results are associated with slower or deeper use. Physicians who are
the first to use the system or are sole users during an encounter are less
inclined to quick and deep use. These effects are intensified for experts.
DISCUSSION: A trade-off between volume and duration is identified. While system
use is overall similar for experts and non-experts, the circumstances in which a
certain profile is more likely to be observed vary across these two groups.
Information availability and multiple-physician dynamics within the encounter
emerge as important for the prediction of use profiles. The findings of this
study provide implications for the design, implementation, and research of HIE
use.
PMID- 28502912
TI - Thinking Styles and Quality of University Life Among Deaf or Hard of Hearing and
Hearing Students.
AB - The authors explored how thinking styles relate to quality of university life
among deaf or hard of hearing (DHH) and hearing university students in mainland
China. The first of two studies affirmed the validity and reliability of a
modified version of the Quality of University Life Measure (QULM; Sirgy,
Grezskowiak, & Rahtz, 2007) among 833 university students (366 DHH, 467 hearing).
The second investigated relationships between thinking styles and quality of
university life; the Thinking Styles Inventory-Revised II (Sternberg, Wagner, &
Zhang, 2007) and modified QULM were administered to 542 students (256 DHH, 286
hearing). Students scoring higher on Type I styles (i.e., more creativity
generating, less structured, cognitively more complex) tended toward greater
satisfaction with university life; those scoring higher on Type II (i.e., more
norm-favoring, more structured, cognitively more simplistic) tended toward less
satisfaction. Contributions, limitations, and implications of the research are
discussed.
PMID- 28502913
TI - Scaffolding the Communication of People With Congenital Deafblindness: An
Analysis of Sequential Interaction Patterns.
AB - The High Quality Communication intervention aims to stimulate interpersonal
communication between individuals with congenital deaf-blindness (CDB) and their
social partners. Found effective in multiple-case experiments, the intervention
is based on Trevarthen's theory of inter-subjective development (Braten &
Trevarthen, 2007), which describes children's innate and developing ability to
share subjective states in interpersonal communication and social partners'
mediating role in this development. One implication of this theory is that social
partners can support the emergence of higher-complexity communication behaviors
in individuals who are still developing these behaviors. To test this
proposition, communication patterns between individuals with CDB and their
parents, teachers, and professional caregivers were analyzed. Analysis of two
event sequences of communicative behaviors showed a highly significant
correspondence between the behavior of the social partner and the subsequent
behavior of the individual with CDB, confirming that social partners can scaffold
higher-complexity communication within interpersonal communication.
PMID- 28502914
TI - Introduction: Sign Language, Sustainable Development, and Equal Opportunities.
PMID- 28502915
TI - A Dialogue on the Multiple Facets of Sustainability.
AB - This chapter contains excerpts from a conversation among the contributors to Sign
Language, Equal Opportunities, and Sustainable Development (De Clerck & Paul,
2016) during a workshop that preceded the International Conference on Sign
Language, Sustainable Development, and Equal Opportunities (Ghent University,
Belgium, April 2014). The objective of the conversation was to illustrate an open
ended, dialogical approach that added an interactive component to the book and
inspired further thoughts and exchanges. Videos of the conversation were posted
online by the European Union of the Deaf at http://www.eud.eu/news/university
gent/.
PMID- 28502916
TI - Perspectives on the Sign Language Factor in Sub-Saharan Africa: Challenges of
Sustainability.
PMID- 28502918
TI - Ability of the Ankle Brachial Index and Brachial-Ankle Pulse Wave Velocity to
Predict the 3-Month Outcome in Patients with Non-Cardioembolic Stroke.
AB - AIM: Both the ankle brachial index (ABI) and brachial-ankle pulse wave velocity
(baPWV) are surrogates for atherosclerosis. In this study, we aimed to evaluate
the ability of ABI and baPWV to predict stroke outcome in patients with first
ever non-cardioembolic stroke. METHODS: This study included consecutive patients
with first-ever non-cardioembolic stroke admitted within 1 week after onset to
Ota Memorial Hospital between January 2011 and December 2013. Baseline
characteristics and National Institutes of Health stroke scale scores at
admission were noted. ABI and baPWV were evaluated within 5 days of admission.
The patients were categorized according to ABI (cut-off 0.9) and baPWV (cut-off
1870 cm/s) determined using the receiver operation curve for poor outcome.
Clinical outcomes were defined based on the modified Rankin scale (mRS) scores 3
months after stroke onset as good (0 and 1) or poor (2-6). RESULTS: A total of
861 patients were available for evaluation. ABI <0.9 and baPWV >1870 cm/s were
associated with poor outcome in the univariate analysis (p<0.001 and p<0.001,
respectively). After adjusting for factors that showed differences between
groups, ABI <0.9 was associated with poor outcome. Among patients with ABI >=
0.9, higher baPWV showed a slight association with poor outcome after adjustment
[odds ratio 1.46 (95% CI 0.95-2.27)]. CONCLUSION: Our study suggests that the
stroke outcome can be predicted using ABI and to an extent using baPWV when ABI
>= 0.9 in patients with non-cardioembolic stroke.
PMID- 28502920
TI - Endostatin as a Biomarker of Basement Membrane Degradation.
PMID- 28502919
TI - Adiponectin and T-Cadherin: a Tree for Biomarkers in ST-Elevation or Non-ST
Elevation Myocardial Infarction.
PMID- 28502917
TI - The Role of Heparin Cofactor II in the Regulation of Insulin Sensitivity and
Maintenance of Glucose Homeostasis in Humans and Mice.
AB - AIM: Accelerated thrombin action is associated with insulin resistance. It is
known that upon activation by binding to dermatan sulfate proteoglycans, heparin
cofactor II(HCII) inactivates thrombin in tissues. Because HCII may be involved
in glucose metabolism, we investigated the relationship between plasma HCII
activity and insulin resistance. METHODS AND RESULTS: In a clinical study,
statistical analysis was performed to examine the relationships between plasma
HCII activity, glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), and
homeostasis model assessment-insulin resistance (HOMA-IR) in elderly Japanese
individuals with lifestyle-related diseases. Multiple regression analysis showed
significant inverse relationships between plasma HCII activity and HbA1c
(p=0.014), FPG (p=0.007), and HOMA-IR (p= 0.041) in elderly Japanese subjects. In
an animal study, HCII+/+ mice and HCII+/- mice were fed with a normal diet or
high-fat diet (HFD) until 25 weeks of age. HFD-fed HCII+/- mice exhibited larger
adipocyte size, higher FPG level, hyperinsulinemia, compared to HFD-fed HCII+/+
mice. In addition, HFD-fed HCII+/- mice exhibited augmented expression of
monocyte chemoattractant protein-1 and tumor necrosis factor, and impaired
phosphorylation of the serine/threonine kinase Akt and AMP-activated protein
kinase in adipose tissue compared to HFD-fed HCII+/+ mice. The expression of
phosphoenolpyruvate carboxykinase and glucose-6-phosphatase was also enhanced in
the hepatic tissues of HFD-fed HCII+/- mice. CONCLUSIONS: The present studies
provide evidence to support the idea that HCII plays an important role in the
maintenance of glucose homeostasis by regulating insulin sensitivity in both
humans and mice. Stimulators of HCII production may serve as novel therapeutic
tools for the treatment of type 2 diabetes.
PMID- 28502921
TI - Umbilical Cord MSCs Reverse D-Galactose-Induced Hepatic Mitochondrial Dysfunction
via Activation of Nrf2/HO-1 Pathway.
AB - Mitochondria are the central hubs for cellular bioenergetics and are crucial to
cell survival. It is well accepted that compromised mitochondrial function is
linked with hepatocytes injury and contribute to progression of liver diseases.
Despite the therapeutic potential of mesenchymal stem cells (MSCs)
transplantation on hepatic disorders have been extensively investigated, the
effects of MSCs on mitochondrial function in liver injury models remain unknown.
Here we investigated the effects of treatment with umbilical cord (UC) MSC in a
rat model of D-galactose (D-Gal) induced liver injury, characterized by organ
damage, oxidative stress and mitochondrial dysfunction. Our results showed that
UC-MSCs treatment significantly alleviated histological lesion and attenuated the
elevation of liver biochemical markers, demonstrating its protective effects on D
Gal induced hepatic disorders. Mitochondria isolated from the liver of D-Gal
models exhibited decreased antioxidant capacity as well as compromised
bioenergetics functions, as shown by a loss of mitochondrial membrane potential,
elevation of reactive oxygen species (ROS) production, reduction of mitochondrial
respiration complexes and ATP decrement. Treatment of rats with UC-MSCs
remarkably blunted these changes and rescued mitochondrial efficiency.
Mechanistically, we found that the protective potential of UC-MSCs administration
was mediated by nuclear factor-E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1)
pathway, but not FOXO3a pathway. In conclusion, the attenuating effects of UC
MSCs on hepatic damage partially rely on normalizing mitochondrial function and
preventing a state of energetic deficit via activation of Nrf2/HO-1 pathway.
PMID- 28502922
TI - Design, Synthesis, and Structure-Activity Relationship Study of Epoxysuccinyl
Peptide Derivatives as Cathepsin B Inhibitors.
AB - Cathepsin B is a lysosomal cysteine protease involved in many diseases. The
present research demonstrates that derivatives of epoxysuccinyl-peptide are
effective and selective cathepsin B inhibitors. We synthesized a series of
epoxysuccinyl-peptide derivatives based on the well-known cathepsin B inhibitor
E64d. Specifically, we substituted the 2-methylpropane group at the R1 position
of E64d with a sulfane, such as ethyl(methyl) sulfane or benzyl(methyl) sulfane.
We also designed and synthesized a library of molecules with various substituents
at the R2 position of E64d to replace 2-methylbutane. By studying the structure
activity relationships of these newly synthesized molecules as cathepsin B
inhibitors, we demonstrated that substituting ethyl(methyl) sulfane for 2
methylbutane (R2) of E64d improves the inhibitory activity and selectivity for
cathepsin B inhibition. Our new cathepsin B inhibitors were highly effective and
selective.
PMID- 28502923
TI - G-protein-coupled receptor signaling through Gpr176, Gz, and RGS16 tunes time in
the center of the circadian clock [Review].
AB - G-protein-coupled receptors (GPCRs) constitute an immensely important class of
drug targets with diverse clinical applications. There are still more than 120
orphan GPCRs whose cognate ligands and physiological functions are not known. A
set of circadian pacemaker neurons that governs daily rhythms in behavior and
physiology resides in the suprachiasmatic nucleus (SCN) in the brain. Malfunction
of the circadian clock has been linked to a multitude of diseases, such as
sleeping disorders, obesity, diabetes, cardiovascular diseases, and cancer, which
makes the clock an attractive target for drug development. Here, we review a
recently identified role of Gpr176 in the SCN. Gpr176 is an SCN-enriched orphan
GPCR that sets the pace of the circadian clock in the SCN. Even without known
ligand, this orphan receptor has an agonist-independent basal activity to reduce
cAMP signaling. A unique cAMP-repressing G-protein subclass Gz is required for
the activity of Gpr176. We also provide an overview on the circadian regulation
of G-protein signaling, with an emphasis on a role for the regulator of G-protein
signaling 16 (RGS16). RGS16 is indispensable for the circadian regulation of cAMP
in the SCN. Developing drugs that target the SCN remains an unfulfilled
opportunity for the circadian pharmacology. This review argues for the potential
impact of focusing on GPCRs in the SCN for the purpose of tuning the body clock.
PMID- 28502924
TI - High Time to Upgrade the Clinical Joint Examination with Complementary
Musculoskeletal Ultrasound -From the Clinician's Finger to the Ultrasound
Transducer.
PMID- 28502925
TI - Therapeutic Response to Twice-daily Rabeprazole on Health-related Quality of Life
and Symptoms in Patients with Refractory Reflux Esophagitis: A Multicenter
Observational Study.
AB - Objective To investigate the effect of twice-daily rabeprazole doses on health
related quality of life in refractory patients. Methods and Patients Reflux
esophagitis patients with an insufficient response to once-daily proton pump
inhibitor therapy (Los Angeles Classification grade A-D) received rabeprazole 10
mg or 20 mg twice daily for 8 weeks. The health-related quality of life (SF-8TM)
and symptoms, using the Frequency Scale for the Symptoms of Gastroesophageal
reflux disease, were evaluated before treatment and at weeks 4 and 8. Endoscopy
was performed at baseline and at weeks 8 and 32 where possible. The rabeprazole
dose was determined by the attending physician. Results There were 1,796 patients
analyzed for the efficacy of the twice-daily treatment. Of these cases, 1,462
were treated with rabeprazole 10 mg twice daily, and 334 were treated with
rabeprazole 20 mg twice daily. The factors that affected the selection of the
twice-daily rabeprazole dose by physicians were evaluated, and as expected,
"endoscopic findings when treatment was started" had a strong effect on the
selection of the rabeprazole dose. With both regimens, health-related quality of
life and subjective symptoms were significantly improved at weeks 4 and 8
compared to baseline (p<0.001). The recurrence rate of erosive esophagitis at
week 32 was 9.7% in rabeprazole twice daily-treated patients and 28.4% in proton
pump inhibitor (PPI) once daily-treated patients. Both regimens were well
tolerated. Conclusion Twice-daily treatment with rabeprazole improved the
subjective symptoms and health-related quality of life in patients with
refractory reflux esophagitis more effectively than the standard once-daily dose.
PMID- 28502926
TI - The Evaluation of the Sputum Antigen Kit in the Diagnosis of Pneumococcal
Pneumonia.
AB - Objective A previously developed sputum antigen detection kit for Streptococcus
pneumoniae enabled the early diagnosis of pneumococcal pneumonia using sputum
samples. We conducted a prospective study to compare the sensitivity of the
sputum and urinary antigen kits. Methods Pneumonia patients who were treated from
April 2014 to September 2015 were recruited for the present study. Patients with
pneumococcal pneumonia who could not participate in the prospective arm of the
study were analyzed in the retrospective arm. Results Nine of the 69 participants
in the prospective study had pneumococcal pneumonia. The sputum antigen kit
results correlated well with the sputum culture results. The sensitivity of the
sputum antigen kit was 88.9% (8/9), which was higher than that of the urinary
antigen kit (5/9; 55.6%). When patients from the retrospective arm of the study
were included, the sensitivity of the sputum culture was 93.5% (29/31), which was
significantly higher than that of the urinary antigen kit (19/31; 60.6%). False
positives were obtained using the sputum antigen kit in four cases. Three of the
four false positives were suspected to have resulted from the administration of
antibiotics prior to the use of the kit; the remaining case likely occurred due
to a false reaction to S. milleri-induced pyothorax. Conclusion Collectively, our
findings suggest that the sputum antigen kit has a higher sensitivity for
detecting S. pneumoniae than the urinary antigen kit. However, the prior
administration of antibiotics can render the sputum culture results negative or
lead to a false-positive result.
PMID- 28502927
TI - Mizoribine Synchronized Methotrexate Therapy should be Considered when Treating
Rheumatoid Arthritis Patients with an Inadequate Response to Various Combination
Therapies.
AB - Objective The objective of this study was to confirm the efficacy of low-dose
mizoribine (MZR), an inhibitor of inosine monophosphate dehydrogenase, as part of
synchronized methotrexate (MTX) therapy for rheumatoid arthritis (RA) patients
with an inadequate response to various combination therapies of MTX, other
synthetic disease-modifying anti-rheumatic drugs (DMARDs) and biological DMARDs.
Methods Low-dose MZR was administered to 56 uncontrolled RA patients being
treated with MTX and various biological DMARDs. The observation period was 12
months, and the disease activity was evaluated based on the Disease Activity
Score in 28 joints (DAS28)-ESR, Simplified Disease Activity Index (SDAI) and
serum MMP-3 level. Results All of the disease activity indices were significantly
improved within three months, and the serum MMP-3 levels were also significantly
decreased around four months after starting low-dose MZR therapy. No patients
experienced any adverse effects. Conclusion The present preliminary findings
suggest that low-dose MZR therapy with MTX should be considered for the treatment
of RA patients with an inadequate response to various combination therapies
including MTX, other synthetic DMARDs and biological DMARDs or in whom increasing
the dose of MTX is difficult for reasons such as adverse effects and
complications.
PMID- 28502928
TI - Endoscopic Submucosal Dissection for Depressed-type Early Adenocarcinoma of the
Terminal Ileum.
AB - We herein report a rare case of ileal adenocarcinoma that was completely removed
by endoscopic submucosal dissection (ESD) without any complications. An 80-year
old man was referred to our hospital to undergo treatment for an ileal tumor.
Conventional colonoscopy showed a reddish depressed lesion that was classified as
type 0-IIc according to the Paris classification. The ileal tumor was
successfully removed en bloc by ESD with a negative surgical margin. The
histological findings showed a well-differentiated adenocarcinoma with no
submucosal or lymphovascular invasion. Colonoscopy and CT performed one year
after ESD showed no local recurrence, stenosis, or lymph node metastasis.
PMID- 28502929
TI - Multifocal Colonic Wall Abscesses during Anti-Tumor Necrosis Factor (TNF)-alpha
Therapy for a Patient with Ulcerative Colitis: A Very Rare Manifestation of
Infectious Complications.
AB - A 24-year-old woman was transferred to our hospital under suspicion of an
exacerbation of her known ulcerative colitis. Colonoscopy revealed an edematous
swelling and multifocal discharge of pus throughout the descending colon,
concurrent with active ulcerative colitis findings in the rectum and sigmoid
colon. Computed tomography showed a thickened wall and multifocal abscesses
within the wall of the descending colon. Two weeks after starting antimicrobial
therapy, she was discharged home. This is the first case report of multifocal
colonic wall abscesses. In order not to increase the risk of serious infection
associated with anti-TNF-alpha therapy, proper qualification and strict
monitoring are essential.
PMID- 28502930
TI - Branch Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas Involving
Type 1 Localized Autoimmune Pancreatitis with Normal Serum IgG4 Levels
Successfully Diagnosed by Endoscopic Ultrasound-guided Fine-needle Aspiration and
Treated without Pancreatic Surgery.
AB - We herein report a 68-year-old man with branch duct intraductal papillary
mucinous neoplasms of the pancreas (BD-IPMNs) involving type 1 localized
autoimmune pancreatitis (AIP) with normal serum IgG4 levels. Although he was
referred to our medical center due to suspicion of pancreatic cancer concomitant
with BD-IPMNs, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA)
revealed a mass suspected of being pancreatic cancer to be type 1 AIP. Steroid
administration notably reduced the mass. Although the clinical diagnosis of
pancreatic masses in patients with IPMN can be occasionally challenging,
performing a pathological examination by EUS-FNA may prevent unnecessary
pancreatic surgery in cases of possible AIP.
PMID- 28502932
TI - Rhabdomyolysis after High Intensity Resistance Training.
AB - Rhabdomyolysis, which is a characteristic occurrence in associated with muscle
cell necrosis, develops due to various causes. We herein report a rare case of a
patient with rhabdomyolysis after high intensity resistance training, in which
markedly elevated levels of serum creatine kinase (CK) and urine myoglobin were
observed. A previously healthy 37-year-old man presented with severe myalgia and
dark urine after performing high-intensity exercise. The patient's serum CK level
was 95,100 U/L and his urine myoglobin level was 160,000 ng/mL. His symptoms and
laboratory findings gradually improved with the intravenous administration of
saline and no complications (including electrolyte imbalance and acute renal
failure) developed.
PMID- 28502931
TI - Graves' Disease in Pediatric and Elderly Patients with 22q11.2 Deletion Syndrome.
AB - 22q11.2 Deletion Syndrome (22qDS) is often complicated by autoimmune diseases. To
clarify the causal relationship, we examined the lymphocyte subset distribution
and the human leucocyte antigen (HLA) in two female patients (one child and an
elderly) with Graves' disease (GD) and 22qDS. Thymus dysgenesis might have
contributed to the T-cell imbalance and the lack of negative selection in both
cases. Notably, HLA-DR14, a known risk factor for GD in Japanese individuals and
the decreased regulatory T-cell numbers that were seen in the pediatric case, may
affect the early onset of GD. Central and peripheral tolerance and Th1 cells
appeared to be associated with the pathogenesis of GD in 22qDS.
PMID- 28502934
TI - A Cryptogenic Case of Fulminant Fibrosing Organizing Pneumonia.
AB - Cryptogenic organizing pneumonia (COP) generally responds well to corticosteroids
with a favorable outcome. Rare cases of organizing pneumonia are rapidly
progressive. Yousem et al. studied pathologic predictors of idiopathic
bronchiolitis obliterans organizing pneumonia/COP with an unfavorable prognosis.
Beardsley and Rassl proposed the name fibrosing organizing pneumonia (FOP). A 74
year-old female non-smoker presented with a 2-week history of dry cough followed
by dyspnea and a fever. The clinical course was fulminant, but we successfully
performed bronchoscopy. After the diagnosis of FOP, we treated the patient with
mechanical ventilation and high-doses of steroids/immunosuppressants, which
improved the disease.
PMID- 28502933
TI - Sustained Tubulointerstitial Inflammation in Kidney with Severe Leptospirosis.
AB - Leptospirosis is frequently associated with acute kidney injury. Some survivors
are known to progress to chronic kidney disease due to sustained
tubulointerstitial inflammation. We present a case of severe leptospirosis with
acute renal failure. Although antibiotic therapy resolved the infection, moderate
renal dysfunction remained. A renal biopsy demonstrated marked inflammatory
infiltration in the tubules and interstitium. Many of the inflammatory cells were
CD68-positive monocytes/macrophages, predominantly M1 phenotype. An intermediate
dose of oral corticosteroids normalized the patient's serum creatinine levels. We
suggest that corticosteroid therapy may be a therapeutic option for some patients
with sustained tubulointerstitial nephritis who survive severe leptospirosis.
PMID- 28502935
TI - Two Cases of Neurolymphomatosis with Fatal Bilateral Vocal Cord Paralysis that
were Diagnosed with 18F-fluorodeoxyglucose Positron Emission Tomography (FDG
PET)/CT.
AB - Neurolymphomatosis is a rare entity defined as nerve infiltration by neurotropic
abnormal lymphocytes which can lead to the development of neuropathy, with
typical presentations including pain, hypoesthesia, paresthesis and palsy. We
herein report two cases where critical bilateral vocal cord paralysis due to
neurolymphomatosis in recurrent nerves occurred in refractory Burkitt lymphoma
and adult T-cell lymphoma patients. High-dose methotrexate and intrathecal
chemotherapy injection for the nervous lesions were ineffective, and the patients
died. Neurolymphomatosis of the recurrent nerve is an emergent and difficult
complication and should be suspected when sudden onset of aphasia, hoarseness or
shortness of breath is found in refractory lymphoma patients.
PMID- 28502936
TI - Successful Treatment of Behcet's Disease Associated with Acute Myeloid Leukemia
with Myelodysplasia-related Changes Using Azacitidine and Tacrolimus before
Allogeneic Hematopoietic Stem Cell Transplantation.
AB - The coexistence of acute myeloid leukemia (AML) with Behcet's disease (BD) is
rare. The optimum treatment for AML-associated BD has not been established. We
herein report a patient with BD who developed AML with myelodysplasia-related
changes. Induction chemotherapy caused complete remission of the AML but worsened
the BD. Thereafter, AML was treated with azacitidine. The BD was steroid
dependent. Tacrolimus was added, which improved the BD. The patient underwent
allogeneic hematopoietic stem cell transplantation (HSCT) and remains in complete
remission for both diseases. Allogeneic HSCT was found to be a potent therapeutic
option for AML-associated BD. In addition, azacitidine and tacrolimus were shown
to be a suitable bridging regimen before HSCT.
PMID- 28502937
TI - Acquired Inhibitors to Multiple Coagulation Factors (V, IX, and XII) Identified
in a Unique Patient with Hepatocellular Carcinoma.
AB - An acquired formation of inhibitors to coagulation factors is a rare type of
coagulopathy. The development of inhibitors for multiple coagulation factors has
never been reported. A 75-year-old Japanese female underwent interventional
therapy for hepatocellular carcinoma. Five days after the last intervention, her
prothrombin time decreased to 10%, and her activated partial thromboplastin time
(APTT) lengthened to 265.1 sec. The activities for coagulation factors showed
significantly reduced activities (<10%) of factors V, IX, and XII. A cross-mixing
test demonstrated an inhibitor pattern, and inhibitory antibodies against factors
V, IX, and XII were detected. We discuss our patient's etiology and pathogenesis.
PMID- 28502938
TI - Successful Treatment of Catastrophic Antiphospholipid Antibody Syndrome
Associated with MALT Lymphoma by Autologous Hematopoietic Stem Cell
Transplantation.
AB - A 37-year-old woman with extranodal marginal-zone lymphoma was admitted with a
fever, hemiplegia, and severe dyspnea after chemotherapy. Catastrophic
antiphospholipid antibody syndrome (CAPS) was suspected based on the
histopathological confirmation of small-pulmonary vessel occlusion, evidence of
the involvement of three organs, and elevated lupus anticoagulant assay results
in a short time span. The patient responded to the initial treatment. One month
later, the CAPS and lymphoma relapsed, and the patient underwent autologous
hematopoietic stem cell transplantation. Complete remission of the lymphoma has
been successfully maintained, and the condition of the patient has remained
stable for two years with no further evidence of thrombosis.
PMID- 28502939
TI - Myelodysplastic Syndrome Developing Presacral Extramedullary Hematopoiesis with
Atypical MRI Findings.
AB - A 64-year-old woman was diagnosed to have refractory cytopenia with multilineage
dysplasia (RCMD) including an increased number of sideroblasts in the bone marrow
(BM). Computed tomography (CT) revealed a presacral mass which showed iso- or
high-intensity signals according to T1-weighted and hypo-intensity signals on T2
weighted magnetic resonance imaging (MRI). CT-guided biopsy revealed the presence
of hematopoietic tissue with features that correlated with the BM findings. While
the formation of extramedullary hematopoiesis in the presacral area is rare, it
is important to differentiate it from other parasacral tumors even though such
differentiation is often difficult. This patient demonstrated atypical MRI
signals possibly due to an increase in the cellular iron content of the erythroid
precursors.
PMID- 28502940
TI - PET Imaging of 18F-FDG, 11C-methionine, 11C-flumazenil, and 11C-4DST in
Progressive Multifocal Leukoencephalopathy.
AB - The use of positron emission tomography (PET) imaging in progressive multifocal
leukoencephalopathy (PML) has rarely been reported. We herein report a set of PET
images in a 63-year-old patient with PML. In PML lesions, the uptake of 18F
fluorodeoxyglucose, 11C-methionine, 11C-flumazenil, and [methyl-11C]4'
thiothymidine was decreased, increased, decreased, and unchanged, respectively.
These results suggest that glucose metabolism decreased, protein synthesis
increased, neuronal integrity decreased, and the DNA synthesis and cellular
proliferation of host cells were not activated in PML lesions. These results may
reflect very little infiltration by inflammatory cells and active infection with
JC virus in this case.
PMID- 28502941
TI - The Sequential Ultrasonographic, Electrophysiological and MRI Findings in a
Patient with the Pharyngeal-cervical-brachial Variant of Guillain-Barre Syndrome
from the Acute Phase to the Chronic Phase.
AB - Acute progressive weakness in bulbar, neck and limbs is included in several
differential diagnoses, including the pharyngeal-cervical-brachial (PCB) variant
of Guillain-Barre syndrome (GBS). Patients with the PCB variant of GBS are
reported to have localized diagnostic cervical spinal nerve abnormalities that
can be examined by nerve ultrasonography (NUS) and magnetic resonance neurography
(MRN). We herein report the case of a 77-year-old man with the PCB variant of
GBS. Although the nerve conduction study (NCS) findings were indirect indicators
for an early diagnosis, the combination of NCS and NUS was a useful complementary
measure that facilitated an early diagnosis. MRN did not show any apparent
diagnostic abnormalities. After early treatment, the patient was discharged and
returned home.
PMID- 28502943
TI - The Development of Cerebral Venous Thrombosis after Tadalafil Ingestion in a
Patient with Antiphospholipid Syndrome.
AB - We report a case of cerebral venous thrombosis related to the ingestion of
tadalafil. A 45-year-old man presented with posterior headache and was diagnosed
with tension headache. Five days later, he was transported to our hospital via
ambulance due to a tonic-clonic seizure. Head MRI showed cerebral venous
thrombosis (CVT). He confessed to having recently taken a large doses of
tadalafil. His anti-cardiolipin antibody and anti-caldiolipin-beta2-glycoprotein
I complex antibody levels were elevated. Our case suggests the possibility that
tadalafil is related to both cardiovascular complications and CVT in patients
with hypercoagulability. Patients with conditions associated with
hypercoagulability, including antiphospholipid syndrome may be better advised to
avoid the use of tadalafil.
PMID- 28502944
TI - Reactive Arthritis Caused by Yersinia enterocolitica Enteritis.
AB - We report a case of reactive arthritis (ReA) triggered by Yersinia enterocolitica
enteritis. A 24-year-old Japanese man developed polyarthritis in the lower limbs.
Two weeks prior to these symptoms, he noted diarrhea, right lower abdominal pain
and a fever. Y. enterocolitica was not isolated from a stool culture; however, he
was diagnosed with ReA based on the colonoscopic findings of a high anti-Y.
enterocolitica antibody titer and HLA-B27 antigen positivity. Following treatment
with methotrexate and steroids, his arthritis improved. This is the first
reported Japanese case of ReA in the English literature after a gastrointestinal
infection caused by Y. enterocolitica.
PMID- 28502942
TI - Brain Biopsy Is More Reliable than the DNA test for JC Virus in Cerebrospinal
Fluid for the Diagnosis of Progressive Multifocal Leukoencephalopathy.
AB - The current standard diagnostic approach for progressive multifocal
leukoencephalopathy (PML) is to perform a DNA test to identify the presence of
the JC virus in cerebrospinal fluid (CSF). A 32-year-old woman with a 5-year
history of systemic lupus erythematosus developed right hemiplegia and motor
aphasia. MRI revealed a large white matter lesion in the left frontal lobe. JC
virus DNA was undetectable in the CSF, but a brain biopsy showed typical
histopathology and a high DNA load of the JC virus. The patient was treated with
mefloquine and mirtazapine, and is currently alive at 24 months after onset. An
early brain biopsy may therefore be important for making a timely diagnosis of
PML.
PMID- 28502945
TI - Sporotrichal Tenosynovitis Diagnosed Helpfully by Musculoskeletal
Ultrasonography.
AB - A 72-year-old man presented with persistent oligoarthritis and positive results
for rheumatoid factor and was suspected of having rheumatoid arthritis (RA).
However, the musculoskeletal ultrasonography (MSUS) findings were not consistent
with those of typical RA. He had undergone surgery for carpal tunnel syndrome,
which allowed both histopathological and microbiological examinations to be
performed. A synovial tissue culture was positive for Sporothrix schenckii, and
he was diagnosed with sporotrichal tenosynovitis. He received anti-fungal
therapy, and the sporotrichal tenosynovitis resolved. This case suggests that
MSUS is a useful modality, and sporotrichal tenosynovitis, though rare, should be
considered in the differential diagnosis of RA.
PMID- 28502946
TI - Two Cases of Thrombocytopenia, Anasarca, Fever, Reticulin Fibrosis/Renal Failure,
and Organomegaly (TAFRO) Syndrome with High Serum Procalcitonin Levels, Including
the First Case Complicated with Adrenal Hemorrhaging.
AB - Thrombocytopenia, Anasarca, Fever, Reticulin fibrosis/Renal failure, and
Organomegaly (TAFRO) syndrome is a recently described systemic inflammatory
disorder characterized by thrombocytopenia, anasarca, fever, reticulin
fibrosis/renal failure, and organomegaly. It has an acute or subacute onset of
unknown etiology, although some pathological features resemble those of
multicentric Castleman disease. We here report two cases of TAFRO syndrome. The
symptoms and pathological findings in these cases met the 2015 diagnostic
criteria. Our cases showed high serum procalcitonin levels, suggesting bacterial
infection as an onset trigger. In addition, Case 1 is the first case complicated
with adrenal hemorrhaging. Case 2 is the second case of tocilizumab-resistant
TAFRO syndrome successfully treated with rituximab.
PMID- 28502949
TI - Pulmonary Cryptococcosis Complicated by Sarcoidosis.
PMID- 28502948
TI - Disseminated Cryptococcosis with Adrenal Insufficiency and Meningitis in an
Immunocompetent Individual.
AB - We present a case of cryptococcosis with adrenal insufficiency and meningitis in
a healthy host without any risk factors. Antifungal therapy did not reduce the
cryptococcal antigen titers of the cerebrospinal fluid and serum or the bilateral
adrenal gland enlargement. It was suggested that the adrenal glands were the
focus of persistent fungemia. Removal of both adrenal glands brought about a
response to antifungal therapy. We conclude that if antifungal therapy is
ineffective, bilateral adrenalectomy is an effective measure for treatment of
such patients. Cryptococcosis is a possible cause of primary adrenal
insufficiency in immunocompetent patients.
PMID- 28502947
TI - Intractable Cutaneous Nontuberculous Mycobacteriosis (Mycobacterium abscessus)
during Treatment for Systemic Lupus Erythematosus.
AB - Mycobacterium abscessus infection tends to occur in patients with an advanced
immunocompromised status. We encountered a case of intractable cutaneous M.
abscessus infection that developed in a patient with systemic lupus erythematosus
(SLE) during maintenance therapy. A 28-year-old woman developed a fever and
redness of the skin on her buttocks. General antibacterial therapy was
ineffective, and acid-fast bacteria were detected in the biopsy that was
conducted to differentiate the dermal symptoms of SLE. The clinical findings
eventually improved; however, the symptoms recurred multiple times during
treatment. Despite recent advances in SLE treatment, M. abscessus infection
remains a considerable complication of SLE.
PMID- 28502950
TI - Colitis Associated with Nintedanib Therapy for Idiopathic Pulmonary Fibrosis
(IPF).
PMID- 28502951
TI - Diffuse Large B-cell Lymphoma Involving the Skeletal Muscle.
PMID- 28502952
TI - Lemierre's Syndrome Variant with External Jugular Vein Thrombosis.
PMID- 28502953
TI - Immune Reconstitution Syndrome in a Patient with AIDS.
PMID- 28502955
TI - Blue light inhibits the enlargement of Erythrobacter litoralis spheroplasts.
PMID- 28502954
TI - Acute Prevertebral Calcific Tendinitis.
PMID- 28502956
TI - Evaluation of biofilm-forming ability of bacterial strains isolated from the roof
of an old house.
AB - The bacterial diversity associated with biofilm-forming ability was studied.
Eighteen bacterial strains were isolated from a microbial film collected from the
roof of an old house located in Sfax, Tunisia. The purity of these microorganisms
was confirmed by microscopic observation after repeated streaking on a Tryptic
Soy agar medium. Biofilm formation was estimated using preliminary tests
including a motility test, microbial adhesion to solvents (MATS), and the Congo
Red Agar method (CRA). Since these tests showed no significant result, microplate
tests, such as crystal violet and resazurin assays, were used. The results
obtained showed that strain S61 was able to form a biofilm within 24 h (OD570 =
4.87). The viability of the S61 biofilm with resazurin assessed with fluorescence
measurement was about 1.5 * 103. The S61 strain was identified as Staphylococcus
epidermidis. In the biofilm studied here, it was the most biofilm-forming
bacterium and will be used as a bacterial model for studying anti-biofilm
activity.
PMID- 28502957
TI - 1-Methoxypyrrole-2-carboxamide-A new pyrrole compound isolated from Streptomyces
griseocarneus SWW368.
AB - A new pyrrole compound, 1-methoxypyrrole-2-carboxamide, was obtained from a
culture broth of Streptomyces griseocarneus SWW368, which was isolated from the
rhizospheric soil under a Para rubber tree (Hevea brasiliensis). The chemical
structure was elucidated by 1D NMR, 2D NMR, and MS, as a pyrrole ring with a N
methoxy group and a primary amide group. It exhibited antibacterial properties
against Kocuria rhizophila, Staphylococcus aureus and Xanthomonas campestris pv.
oryzae; however, cytotoxicity of the compound at 714 MUM against several
mammalian tumor cell lines, i.e. A549, PANC1, HT29, HT1299 and HeLa S3, were not
detected.
PMID- 28502958
TI - A Complicated Case of Pregnancy Involving a Presacral Epidermoid Cyst.
AB - Although presacral developmental cysts, including epidermoid cysts, are
relatively rare diseases, an intrapelvic mass found for the first time in early
pregnancy should be followed-up with the possibility of presacral developmental
cysts in mind to be alert to the signs of local infection and malignancy. We
treated a pregnant patient with presacral cystic disease. During pregnancy,
percutaneous fenestration was performed because the cyst caused severe
compression symptoms and complicated bacterial infection. Laparoscopic total cyst
excision was performed after cesarean section. There is no suggested criterion to
make a decision for the delivery mode. The mass should be removed completely to
reduce the risk of recurrence and malignant progression.
PMID- 28502959
TI - Squamous Cell Carcinomas on Bilateral Feet Arising in Long-Standing Eczematous
Lesions.
AB - We present a woman with squamous cell carcinomas on both feet in long-standing
eczematous lesions. Histopathological examination of biopsies from the both feet
revealed highly atypical cells invading the reticular layer of the dermis in the
hyperkeratotic lesion and they were associated with surrounding dermatitis with
spongiosis. Although the cause and etiology of eczema in our case is unclear, we
speculate that the exceptionally long-lasting dermatitis might have induced
double SCCs on bilateral feet with an unusual constitution. To the best of our
knowledge, this is a first case of SCC on bilateral feet arising in long-standing
eczematous lesions.
PMID- 28502960
TI - Circulating Anti-Nuclear Antibodies in Systemic Sclerosis: Utility in Diagnosis
and Disease Subsetting.
AB - The presence of circulating anti-nuclear antibodies (ANAs) is a hallmark of
immune dysregulation in patients with systemic sclerosis (SSc). Currently, a
variety of SSc-specific ANAs, including anticentromere, anti-topoisomerase I, and
anti-RNA polymerase III antibodies, have been well characterized, and their
commercial kits are available worldwide. Since these autoantibodies are
specifically detected in SSc patients and are associated with unique sets of
disease manifestations, they are widely used in routine clinical practice for
diagnosis, clinical subgrouping, and prediction of future organ involvements and
prognosis. In addition, SSc-specific ANAs are also useful in predicting future
development of SSc in patients with Raynaud's phenomenon without any scleroderma
skin changes, because their production often precedes onset of SSc symptoms.
Application of circulating SSc-specific ANA measurement to clinical practice has
greatly improved patient care, but utility of the autoantibody testing could be
maximized by combining other clinical information, such as degree and extent of
skin thickness and disease duration.
PMID- 28502962
TI - Treatment Results of Transurethral Resection of the Prostate by Non-Japanese
Board-Certified Urologists for Benign Prostate Hyperplasia: Analysis by Resection
Volume.
AB - INTRODUCTION: Transurethral resection of the prostate (TURP) is the gold standard
for surgical treatment of benign prostatic hyperplasia (BPH), but it has
complications such as bleeding and transurethral resection syndrome. The
treatment results of TURP performed by non-Japanese board-certified urologists
were examined, and the results were analyzed according to the resection volume to
determine how much resection volume was suitable for non-Japanese board-certified
urologists. MATERIALS AND METHODS: A total of 72 cases that underwent TURP for
BPH at our hospital were examined. The patients were divided into three groups by
resection volume (<20 g, 20-30 g, >30 g). The operators were five non-Japanese
board-certified urologists. Various clinical factors were examined among the
three groups before and after TURP. RESULTS: The average operation time and
resection volume were significantly different among the groups. There were more
transfused cases with greater resection volume. The changes from before to after
TURP in the International Prostate Symptom Score, total prostate volume, and
maximum flow rate were significantly different among the three groups, but the
rates of these changes were not. CONCLUSIONS: In this study, TURP performed by
non-Japanese board-certified urologists was relatively safe and achieved
sufficient efficacy. Cases with resection volume less than 20 g appear the most
appropriate for non-Japanese board-certified urologists.
PMID- 28502961
TI - Haptoglobin Reduces Inflammatory Cytokine INF-gamma and Facilitates Clot
Formation in Acute Severe Burn Rat Model.
AB - Haptoglobin exerts renal protective function by scavenging free hemoglobin from
the urine and blood stream in patients with hemolytic disorders. Recent studies
elucidate the relationships between haptoglobin and inflammation. In addition,
coagulopathy is often induced by systemic inflammation characterized by the
presence of vascular endothelial damage. We hypothesize that haptoglobin might
have an anti-inflammatory effect and affect hypercoagulability using rat burn
model. Thirty anesthetized rats of six-weeks of age received over 30% full
thickness scald burn on the dorsal skin surface. All rats were injected with
either haptoglobin (Hpt) or normal saline (NS) intraperitoneally. The rats were
divided into three groups: 1) control group (NS 20 mL/kg); 2) low concentration
of Hpt group, L-Hpt, (Hpt 4 mL (80 U) /kg+NS 16 mL/kg); and 3) high concentration
of Hpt group, H-Hpt, (Hpt 20 mL (400 U) /kg). While under anesthesia, all rats
were euthanized by exsanguination at 6 hours (N=5) and 24 hours (N=5).
Inflammatory and anti-inflammatory cytokines were measured and whole-blood
viscoelastic tests were performed by thromboelastometry (ROTEM). Haptoglobin
significantly reduced free hemoglobin 24 hours after the injury. Improvement of
hematuria was confirmed in the H-Hpt group. There were no differences in thrombin
antithrombin complex and plasmin-alpha2 plasmin inhibitor complex. The
haptoglobin tended to decrease interferon-gamma (IFN-gamma) in H-Hpt group. ROTEM
findings of the L-Hpt group showed significantly higher clot firmness and shorter
time to maximum clot formation velocity than the control group. Haptoglobin
reduced INF-gamma, and accelerated speed of clot formation in acute phase of
severe burn.
PMID- 28502963
TI - A Case of Syringocystadenoma Papilliferum with Tubular Papillary Adenoma of the
Chest.
AB - We report a case of syringocystadenoma papilliferum (SCAP) combined with tubular
papillary adenoma (TPA) arising on the chest of a 45-year-old Japanese woman.
Histopathological examination revealed the characteristic findings of SCAP in the
superficial part of the lesion and those of TPA in the deeper part. We reviewed
the English literature about this combination. SCAP and TPA have the same
cellular components, but show differences of the general structure. The
combination of these two neoplasms is more frequent than expected by most
dermatopathologists or pathologists. This combination is frequently seen in
patients with nevus sebaceus (NS), but it is also found in patients without NS.
PMID- 28502964
TI - Primary Volvulus of the Small Intestine Exhibiting Chylous Ascites: A Case
Report.
AB - BACKGROUND: Primary volvulus of the small intestine associated with chylous
ascites is very rare, with only four reported cases. In this paper, we report a
new case of primary volvulus associated with chylous ascites. CASE PRESENTATION:
The patient was a 70-year-old man. After experiencing bloating and abdominal pain
for several hours, he called an ambulance and underwent an emergency examination
at our hospital. Abdominal distension, pressure pain, and rebound tenderness were
observed throughout his entire abdomen. The patient had a history of hypertension
for which he was receiving oral treatment. Abdominal contrast-enhanced computed
tomography (CT) revealed an edematous change in the intestinal membrane and
volvulus of the small intestine. As findings suggestive of ischemia were observed
in part of the intestines, emergency surgery was performed on the day of
admission. Open surgery revealed approximately 500 mL of chylous ascites in the
abdominal cavity. The small intestine had twisted 180 degrees in a counter
clockwise direction at the root of the superior mesenteric artery, and the
mesentery appeared milky white with edematous changes extending 75 to 240 cm from
the ligament of Treitz. There was no evidence of intestinal necrosis; therefore
intestinal resection was not performed. The volvulus of the small intestine was
corrected. Moreover, because there was no other underlying disease observed,
surgery was completed. The ascites collected during surgery revealed high levels
of triglycerides at 332 mg/dL, and chylous ascites was diagnosed. An abdominal CT
performed on the third day after surgery showed an improvement in intestinal
edema, and primary volvulus of the small intestine associated with chylous
ascites was diagnosed. Postoperative progress was good, and the patient was
discharged on hospital day 10.
PMID- 28502965
TI - Primary Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma with a Nodular
Opacity: Report of a Case.
AB - Herein, we describe our experience in treating a case of primary pulmonary mucosa
associated lymphoid tissue lymphoma detected as a nodular opacity. A 79-year-old
man was referred to our hospital. Computed tomography showed a nodular opacity
measuring 20 mm in diameter with regular margins in segment 5 of the right middle
lobe of the lung. Although the bronchoscopic brush cytology result was class III,
the patient was tentatively diagnosed with suspected mucosa-associated lymphoid
tissue lymphoma. A thoracoscopic right middle lobectomy was performed. The
pathological findings showed nodular proliferation of small to medium-sized,
mature-appearing atypical lymphoid cells, lymphoepithelial lesions, and vague
follicles suggesting follicular colonization in some areas. The patient was
diagnosed with low-grade small B-cell lymphoma and mucosa-associated lymphoid
tissue lymphoma. He has remained well to date, 23 months after surgery, without
evidence of recurrence.
PMID- 28502966
TI - Laparoscopic Repair of Vaginal Evisceration after Abdominal Hysterectomy for
Uterine Corpus Cancer: A Case Report and Literature Review.
AB - Vaginal cuff dehiscence is a rare but serious complication that can develop after
hysterectomy. Emergent surgical intervention is required for vaginal cuff
dehiscence due to the potential subsequent vaginal evisceration, which may lead
to necrosis of the small bowel. A 62-year-old nulliparous woman with a 30-year
history of smoking, diabetes mellitus, and rheumatoid arthritis (treated with
oral steroids) presented with a vaginal cuff dehiscence. Thirty-eight days before
the admission, she had undergone a radical operation including total abdominal
hysterectomy for uterine corpus cancer at another hospital. We performed emergent
laparoscopic surgery to reduce the prolapsed small bowel into the abdominal
cavity and repaired the vaginal cuff with a two-layer continuous closure using
absorbable barbed sutures. The patient experienced no postoperative
complications, and no recurrence of the vaginal cuff dehiscence occurred. Vaginal
cuff dehiscence and evisceration can be surgically managed using an abdominal,
vaginal, or laparoscopic approach, and the choice of method should be based on
patient characteristics and the surgeon's skills. Laparoscopic vaginal cuff
repair with a two-layer continuous closure using absorbable barbed sutures is a
minimally invasive technique that is safe and effective for medically stable
patients with no small bowel injury or vascular compromise and no pelvic abscess.
PMID- 28502967
TI - Neck and Occipital Pain Caused by Deep Cervical Intramuscular Lipoma: A Surgical
Case.
AB - A lipoma is a slow-growing, benign tumor and is usually asymptomatic; hence,
surgical intervention can often be avoided in patients with these tumors in the
cervical and cranial area. Lipomas arise most commonly in the subcutaneous fat,
but occasionally in muscle tissue. Intramuscular lipomas in the cervico-cranial
area have rarely been reported. We describe here a patient with a large
intramuscular lipoma in the deep cervical tissue. The patient experienced
troublesome pain in the neck and occipital area, and surgical treatment was
therefore suggested. Particularly in the cervical area, intramuscular lipomas
sometimes invade the surrounding muscles and tissue layers and develop into an
irregular mass, despite being benign. In addition, the cervical area has one of
the most complex muscle structures. Nevertheless, surgical management of
intramuscular lipoma in the cervical and cranial area is sometimes indicated, for
example, in patients with clinical symptoms or masses with a tendency to grow
large.
PMID- 28502968
TI - Prokaryotic Communities at Different Depths between Soils with and without Tomato
Bacterial Wilt but Pathogen-Present in a Single Greenhouse.
AB - The characterization of microbial communities that promote or suppress soil-borne
pathogens is important for controlling plant diseases. We compared prokaryotic
communities in soil with or without the signs of tomato bacterial wilt caused by
Ralstonia solanacearum. Soil samples were collected from a greenhouse at two
different depths because this pathogen is present in deep soil. We used samples
from sites in which we detected phcA, a key gene regulating R. solanacearum
pathogenicity. The pyrosequencing of prokaryotic 16S rRNA sequences in four soil
samples without disease symptoms but with phcA and in two soil samples with
disease symptoms indicated that community richness was not significantly
different between these two soils; however, microbial diversity in the lower soil
layer was higher in soil samples without disease symptoms but with phcA. A
difference in prokaryotic community structures between soil samples with and
without bacterial wilt was only observed in the upper soil layer despite apparent
similarities in the communities at the phylum level. Proteobacteria,
Acidobacteria, Chloroflexi, Verrucomicrobia, and several Archaea were more
abundant in soil samples without disease symptoms, whereas taxa in another eight
phyla were more abundant in soil samples with disease symptoms. Furthermore, some
prokaryotic taxa were abundant specifically in the lower layer of soil,
regardless of whether disease was present. These prokaryotic taxa may suppress or
accelerate the pathogenesis of bacterial wilt and are good targets for future
studies on disease control.
PMID- 28502969
TI - Transcription of [FeFe]-Hydrogenase Genes during H2 Production in Clostridium and
Desulfovibrio spp. Isolated from a Paddy Field Soil.
AB - Changes in the relative abundances of the transcripts of hydA gene paralogs for
[FeFe]-hydrogenase in Clostridium sp. strain H2 and Desulfovibrio sp. strain A1
isolated from paddy field soil were analyzed during H2 production. Strains H2 and
A1 had at least five and two phylogenetically different hydA genes, respectively.
The relative abundances of their hydA transcripts differed among the paralogs and
H2 production activity changed in a manner that depended on the growth phase and
conditions. Increases or decreases in the relative abundances of the transcripts
of two out of five hydA genes in strain H2 correlated with changes in H2
production rates, whereas those of the others remained unchanged or decreased. In
strain A1, the relative abundances of the transcripts of two hydA genes differed
between monoculture, sulfate-reducing, and syntrophic, methanogenic conditions.
The relative abundance of the transcripts of one hydA gene, predicted to encode a
cytosolic [FeFe]-hydrogenase, was higher under syntrophic, methanogenic
conditions than sulfate-reducing conditions, while that of the transcripts of the
other hydA gene decreased with time under both conditions. This study showed that
the transcription of the hydA gene during growth with active H2 production was
differently regulated among the paralogs in H2 producers isolated from paddy
field soil.
PMID- 28502970
TI - Is Regular Screening for Intracranial Aneurysm Necessary in Patients with
Autosomal Dominant Polycystic Kidney Disease? A Systematic Review and Meta
analysis.
AB - BACKGROUND: The prevalence of intracranial aneurysm in patients with autosomal
dominant polycystic kidney disease (ADPKD) is higher than that among the general
population. We performed a systematic review and meta-analysis on the prevalence
and natural history of intracranial aneurysm among patients with ADPKD. METHODS:
Medline, Embase, Web of Science and Scopus, from inception to July 2016, were
searched for studies reporting the occurrence of intracranial aneurysms among
participants with ADPKD. Two authors independently assessed the eligibility of
all retrieved studies and extracted data. Information on the prevalence of
intracranial aneurysms and their natural history in participants with ADPKD was
collected from all included studies. RESULTS: Fifteen studies with 1,490
participants with ADPKD were pooled to study about the prevalence of intracranial
aneurysm in participants with ADPKD, and the prevalence rate was found to be 10%
(95% CI 7-13%). Studies from China, Japan and Europe (Germany, Poland) reported a
higher prevalence of intracranial aneurysm. Having a family history of
haemorrhagic stroke or intracranial aneurysm was a risk factor for aneurysm
occurrence. Twenty-three percent (95% CI 15-31%) of the participants had multiple
aneurysms. Most of the aneurysms were small (<6 mm) and located in the anterior
circulation. Five studies with 171 participants (83 with 106 aneurysms at
baseline and 88 without) were analyzed to understand the natural history of
aneurysms, with an incidence of aneurysm growth, new aneurysm and aneurysm
rupture of 1.84% (followed up for 435 person-years), 0.57% (1,227 person-years)
and 0.13% (792 person-years) respectively. CONCLUSIONS: Screening for
intracranial aneurysm is recommended in patients with ADPKD when there is a
family history of haemorrhagic stroke or intracranial aneurysm and when they are
from China, Japan or Europe (Germany, Poland). Based on existing data, regular
imaging follow-up is not supported. High-quality, prospective studies are needed
in the future.
PMID- 28502971
TI - Targeting the KEAP1-NRF2 System to Prevent Kidney Disease Progression.
AB - BACKGROUND: Nuclear factor erythroid 2-related factor 2 (NRF2) is a critical
transcription factor for the antioxidative stress response and it activates a
variety of cytoprotective genes related to redox and detoxification. NRF2
activity is regulated by the oxidative-stress sensor molecule Kelch-like ECH
associated protein 1 (KEAP1) that induces proteasomal degradation of NRF2 through
ubiquitinating NRF2 under unstressed conditions. Because oxidative stress is a
major pathogenic and aggravating factor for kidney diseases, the KEAP1-NRF2
system has been proposed to be a therapeutic target for renal protection.
SUMMARY: Oxidative-stress molecules, such as reactive oxygen species, accumulate
in the kidneys of animal models for acute kidney injury (AKI), in which NRF2 is
transiently and slightly activated. Genetic or pharmacological enhancement of
NRF2 activity in the renal tubules significantly ameliorates damage related to
AKI and prevents AKI progression to chronic kidney disease (CKD) by reducing
oxidative stress. These beneficial effects of NRF2 activation highlight the KEAP1
NRF2 system as an important target for kidney disease treatment. However, a phase
3 clinical trial of a KEAP1 inhibitor for patients with stage 4 CKD and type-2
diabetes mellitus (T2DM) was terminated due to the occurrence of cardiovascular
events. Because recent basic studies have accumulated positive effects of KEAP1
inhibitors in moderate stages of CKD, phase-2 trials have been restarted. The
data from the ongoing projects demonstrate that a KEAP1 inhibitor improves the
glomerular filtration rate in patients with stage 3 CKD and T2DM without safety
concerns. Key Message: The KEAP1-NRF2 system is one of the most promising
therapeutic targets for kidney disease, and KEAP1 inhibitors could be part of
critical therapies for kidney disease.
PMID- 28502972
TI - Distribution, Innervation, and Cellular Organization of Taste Buds in the Sea
Catfish, Plotosus japonicus.
AB - The gustatory system of the sea catfish Plotosus japonicus, like that of other
catfishes, is highly developed. To clarify the details of the morphology of the
peripheral gustatory system of Plotosus, we used whole-mount immunohistochemistry
to investigate the distribution and innervation of the taste buds within multiple
organs including the barbels, oropharyngeal cavity, fins (pectoral, dorsal, and
caudal), and trunk. Labeled taste buds could be observed in all the organs
examined. The density of the taste buds was higher along the leading edges of the
barbels and fins; this likely increases the chance of detecting food. In all the
fins, the taste buds were distributed in linear arrays parallel to the fin rays.
Labeling of nerve fibers by anti-acetylated tubulin antibody showed that the
taste buds within each sensory field are innervated in different ways. In the
barbels, large nerve bundles run along the length of the organ, with fascicles
branching off to innervate polygonally organized groups of taste buds. In the
fins, nerve bundles run along the axis of fin rays to innervate taste buds lying
in a line. In each case, small fascicles of fibers branch from large bundles and
terminate within the basal portions of the taste buds. Serotonin
immunohistochemistry demonstrated that most of the taste buds in all the organs
examined contained disk-shaped serotonin-immunopositive cells in their basal
region. This indicates a similar organization of the taste buds, in terms of the
existence of serotonin-immunopositive basal cells, across the different sensory
fields in this species.
PMID- 28502973
TI - The job competency of radiological technologists in Korea based on specialists
opinion and questionnaire survey.
AB - PURPOSE: Although there are over 40,000 licensed radiological technologists (RTs)
in Korea, job competency standards have yet to be defined. This study aims to
clarify the job competency of Korean RTs. METHODS: A task force team of 11
professional RTs were recruited in order to analyze the job competency of
domestic and international RTs. A draft for the job competency of Korean RTs was
prepared. A survey was then conducted sampling RTs and the attitudes of their
competencies were recorded from May 21 to July 30, 2016. RESULTS: We identified
five modules of professionalism, patient management, health and safety, operation
of equipment, and procedure management and 131 detailed job competencies for RTs
in Korea. "Health and safety" had the highest average score and "professionalism"
had the lowest average score for both job performance and importance. The content
validity ratios for the 131 subcompetencies were mostly valid. CONCLUSION:
Establishment of standard guidelines for RT job competency for multidisciplinary
healthcare at medical institutions may be possible based on our results, which
will help educators of RT training institutions to clarify their training and
education.
PMID- 28502974
TI - Efficacy and Prognostic Value of Partial Sensory Rhizotomy and Microvascular
Decompression for Primary Trigeminal Neuralgia: A Comparative Study.
AB - BACKGROUND This study aimed to compare the efficacy and prognostic value of
partial sensory rhizotomy (PSR) and microvascular decompression (MVD) for primary
trigeminal neuralgia (PTN). MATERIAL AND METHODS From June 2010 to June 2012, 117
patients with PTN were recruited for the study, of which 52 cases were treated
with MVD (the MVD group) and 65 cases were treated with PSR (the PSR group).
Visual Analog Scoring (VAS) was performed at 1 and 2 weeks, and at 1, 3, and 6
month after surgery. The overall response rate (ORR) was determined 1 month after
surgery. Barrow Neurological Institute score was adopted to value the
reoccurrence at 6, 12, 24, and 36 months after surgery. A 3-year follow-up was
conducted and the complications were recorded. RESULTS The ORR 2 weeks after
surgery in the MVD and PSR groups was 98.08% and 84.62%, respectively. One and 2
weeks after surgery, the VAS was lower in the MVD group than in the PSR group,
but there was no significant difference in VAS between the 2 groups at 1, 3, and
6 months after surgery. Three years after surgery, the recurrence rate was
significantly lower in the MVD group than in the PSR group. The recurrence-free
survival time was longer in the MVD group than in the PSR group. The occurrence
rates of herpes and total postoperative complications were significantly higher
in the PSR group than in the MVD group. CONCLUSIONS Compared with PSR, MVD is
more suitable for PTN treatment, with less disturbance, lower recurrence rate,
and better efficacy.
PMID- 28502975
TI - An Unusual Presentation of Acute Fibrinous and Organizing Pneumonia.
AB - BACKGROUND Acute fibrinous and organizing pneumonia (AFOP) is a newly evolving
rare non-infectious lung pathology, characterized by intra-alveolar fibrin balls
on histology. It is often difficult to diagnose and is usually mistaken for other
lung pathologies. We present an interesting case of AFOP with unusual radiologic
findings and disease course. CASE REPORT A 56-year-old woman presented with a 1
day history of high-grade fever, chills, and profuse sweating. She was febrile to
101.2 degree Fahrenheit on presentation. On physical examination, she had
decreased air entry in the left upper lobe of the lung. Laboratory testing showed
a white cell count of 27,000 cells per microliter of blood with left shift. A
chest radiograph showed a left upper lobe consolidation. Computed tomography (CT)
of the chest without intravenous contrast showed advanced centrilobular emphysema
and left upper lobe consolidation measuring 6.2*5.9 cm. The patient was started
on antibiotics. She clinically improved and was discharged on oral antibiotics.
After discharge, a trans-bronchial lung biopsy showed acute inflammatory cell
infiltrate with intra-alveolar fibrin balls but no hyaline membrane formation or
significant eosinophils. These findings were consistent with acute fibrinous and
organizing pneumonia. However, she was subsequently lost to follow-up.
CONCLUSIONS Our case adds to the literature a new and unusual finding of upper
lobe infiltrates, in contrast to most cases presenting as bilateral lower lobe
infiltrates. In our case, symptomatic improvement after antibiotic treatment
suggests a possible role of antibiotics in management of this entity.
PMID- 28502976
TI - Technology: Nucleic acid detection - it's elementary with SHERLOCK!
PMID- 28502978
TI - The opioid receptor triple agonist DPI-125 produces analgesia with less
respiratory depression and reduced abuse liability.
AB - Opioid analgesics remain the first choice for the treatment of moderate to severe
pain, but they are also notorious for their respiratory depression and addictive
effects. This study focused on the pharmacology of a novel opioid receptor mixed
agonist DPI-125 and attempted to elucidate the relationship between the delta-,
MU- and kappa-receptor potency ratio and respiratory depression and abuse
liability. Five diarylmethylpiperazine compounds (DPI-125, DPI-3290, DPI-130,
KUST202 and KUST13T02) were selected for this study. PKA fluorescence
redistribution assays in CHO cells individually expressing delta-, MU- or kappa
receptors were used to measure the agonist potency. The respiratory safety
profiles were estimated in rats by the ratio of ED50 (pCO2 increase)/ED50
(antinociception). The abuse liability of DPI-125 was evaluated with a self
administration model in rhesus monkeys. The observed agonist potencies of DPI-125
for delta-, MU- and kappa-opioid receptors were 4.29+/-0.36, 11.10+/-3.04, and
16.57+/-4.14 nmol/L, respectively. The other four compounds were also mixed
agonists with varying potencies. DPI-125 exhibited a high respiratory safety
profile, clearly related to its high delta-receptor potency. The ratio of the
EC50 potencies for the MU- and delta-receptors was found to be positively
correlated with the respiratory safety ratio. DPI-125 has similar potencies for
MU- and kappa-receptors, which is likely the reason for its reduced abuse
potential. Our results demonstrate that the opioid receptor mixed agonist DPI-125
is safer and less addictive than traditional MU-agonist analgesics. These
findings suggest that the development of delta>MU~kappa opioid receptor mixed
agonists is feasible, and such compounds could represent a promising class of
potent analgesics with wider therapeutic windows.
PMID- 28502979
TI - Chrysin ameliorates podocyte injury and slit diaphragm protein loss via
inhibition of the PERK-eIF2alpha-ATF-CHOP pathway in diabetic mice.
AB - Glomerular epithelial podocytes are highly specialized cells that play a crucial
role in maintaining normal function of the glomerular filtration barrier via
their foot processes. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid found
in propolis and mushrooms that has anti-inflammatory, antioxidant and anticancer
properties. This study aimed to evaluate the renoprotective effects of chrysin on
podocyte apoptotic loss and slit diaphragm protein deficiency in high glucose
exposed podocytes and in db/db mouse kidneys. Exposure to high glucose (33
mmol/L) caused glomerular podocyte apoptosis in vitro, which was dose-dependently
attenuated by nontoxic chrysin (1-20 MUmol/L) through reduction of DNA
fragmentation. Chrysin treatment dose-dependently restored the increased Bax/Bcl
2 ratio, and suppressed Apaf-1 induction and the elevated cytochrome c release in
high glucose-exposed renal podocytes. In diabetic db/db mice, oral administration
of chrysin (10 mg.kg-1.d-1, for 10 weeks) significantly attenuated proteinuria,
and alleviated the abnormal alterations in glomerular ultrastructure,
characterized by apoptotic podocytes and foot process effacement. In addition,
this compound improved the induction of slit diaphragm proteins podocin/nephrin
in the diabetic glomeruli. Exposure to high glucose elevated the unfolded protein
response (UPR) to ER stress in renal podocytes, evidenced by up-regulation of
PERK-eIF2alpha-ATF4-CHOP. Chrysin treatment blocked such ER stress responses
pertinent to podocyte apoptosis and reduced synthesis of slit diaphragm proteins
in vitro and in vivo. These observations demonstrate that targeting ER stress is
an underlying mechanism of chrysin-mediated amelioration of diabetes-associated
podocyte injury and dysfunction.
PMID- 28502977
TI - The evolutionary significance of polyploidy.
AB - Polyploidy, or the duplication of entire genomes, has been observed in
prokaryotic and eukaryotic organisms, and in somatic and germ cells. The
consequences of polyploidization are complex and variable, and they differ
greatly between systems (clonal or non-clonal) and species, but the process has
often been considered to be an evolutionary 'dead end'. Here, we review the
accumulating evidence that correlates polyploidization with environmental change
or stress, and that has led to an increased recognition of its short-term
adaptive potential. In addition, we discuss how, once polyploidy has been
established, the unique retention profile of duplicated genes following whole
genome duplication might explain key longer-term evolutionary transitions and a
general increase in biological complexity.
PMID- 28502980
TI - W2476 ameliorates beta-cell dysfunction and exerts therapeutic effects in mouse
models of diabetes via modulation of the thioredoxin-interacting protein
signaling pathway.
AB - Recent evidence shows that high glucose levels recruit carbohydrate response
element-binding protein, which binds the promoter of thioredoxin-interacting
protein (txnip), thereby regulating its expression in beta-cells. Overexpression
of txnip not only induces beta-cell apoptosis but also reduces insulin
production. Thus, the discovery of compounds that either inhibit TXNIP activity
or suppress its expression was the focus of the present study. INS-1E cells
stably transfected with either a txnip proximal glucose response element
connected to a luciferase reporter plasmid (BG73) or full-length txnip promoter
connected to a luciferase reporter plasmid (CL108) were used in primary and
secondary high-throughput screening campaigns, respectively. From 256 000
synthetic compounds, a small molecule compound, W2476 [9-((1-(4-acetyl-phenyloxy)
ethyl)-2-)adenine], was identified as a modulator of the TXNIP-regulated
signaling pathway following the screening and characterized using a battery of
bioassays. The preventive and therapeutic properties of W2476 were further
examined in streptozotocin-induced diabetic and diet-induced obese mice.
Treatment with W2476 (1, 5, and 15 MUmol/L) dose-dependently inhibited high
glucose-induced TXNIP expression at the mRNA and protein levels in INS-1E cells
and rat pancreatic islets. Furthermore, W2476 treatment prevented INS-1E cells
from apoptosis induced by chronic exposure of high glucose and enhanced insulin
production in vitro. Oral administration of W2476 (200 mg.kg-1.d-1) rescued
streptozotocin-induced diabetic mice by promoting beta-cell survival and
enhancing insulin secretion. This therapeutic property of W2476 was further
demonstrated by its ability to improve glucose homeostasis and insulin
sensitivity in diet-induced obese mice. Thus, chemical intervention of the TXNIP
regulated signaling pathway might present a viable approach to manage diabetes.
PMID- 28502981
TI - Mechanisms of gene flow in archaea.
AB - Archaea are diverse, ecologically important, single-celled microorganisms. They
have unique functions and features, such as methanogenesis and the composition of
their cell envelope, although many characteristics are shared with the other
domains of life, either through ancestry or through promiscuous horizontal gene
transfer. The exchange of genetic material is a major driving force for genome
evolution across the tree of life and has a role in archaeal speciation,
adaptation and maintenance of diversity. In this Review, we discuss our current
knowledge of archaeal mechanisms of DNA transfer and highlight the role of gene
transfer in archaeal evolution.
PMID- 28502984
TI - Diabetic nephropathy: Glucose metabolic flux in DN.
PMID- 28502982
TI - Why are hematopoietic stem cells so 'sexy'? on a search for developmental
explanation.
AB - Evidence has accumulated that normal human and murine hematopoietic stem cells
express several functional pituitary and gonadal sex hormones, and that, in fact,
some sex hormones, such as androgens, have been employed for many years to
stimulate hematopoiesis in patients with bone marrow aplasia. Interestingly, sex
hormone receptors are also expressed by leukemic cell lines and blasts. In this
review, I will discuss the emerging question of why hematopoietic cells express
these receptors. A tempting hypothetical explanation for this phenomenon is that
hematopoietic stem cells are related to subpopulation of migrating primordial
germ cells. To support of this notion, the anatomical sites of origin of
primitive and definitive hematopoiesis during embryonic development are tightly
connected with the migratory route of primordial germ cells: from the proximal
epiblast to the extraembryonic endoderm at the bottom of the yolk sac and then
back to the embryo proper via the primitive streak to the aorta-gonado
mesonephros (AGM) region on the way to the genital ridges. The migration of these
cells overlaps with the emergence of primitive hematopoiesis in the blood islands
at the bottom of the yolk sac, and definitive hematopoiesis that occurs in
hemogenic endothelium in the embryonic dorsal aorta in AGM region.
PMID- 28502985
TI - Transplantation: Anti-viral therapy enables transplantation of HCV+ kidneys.
PMID- 28502986
TI - Autoimmunity: HLA-mediated protection in Goodpasture disease.
PMID- 28502987
TI - Early social isolation impairs development, mate choice and grouping behaviour of
predatory mites.
AB - The social environment early in life is a key determinant of developmental,
physiological and behavioural trajectories across vertebrate and invertebrate
animals. One crucial variable is the presence/absence of conspecifics. For
animals usually reared in groups, social isolation after birth or hatching can be
a highly stressful circumstance, with potentially long-lasting consequences.
Here, we assessed the effects of social deprivation (isolation) early in life,
that is, absence of conspecifics, versus social enrichment, that is, presence of
conspecifics, on developmental time, body size at maturity, mating behaviour and
group-living in the plant-inhabiting predatory mite Phytoseiulus persimilis.
Socially deprived protonymphs developed more slowly and were less socially
competent in grouping behaviour than socially enriched protonymphs. Compromised
social competence in grouping behaviour was evident in decreased activity, fewer
mutual encounters and larger interindividual distances, all of which may entail
severe fitness costs. In female choice/male competition, socially deprived males
mated earlier than socially enriched males; in male choice/female competition,
socially deprived females were more likely to mate than socially enriched
females. In neither mate choice situation did mating duration or body size at
maturity differ between socially deprived and enriched mating opponents. Social
isolation-induced shifts in mating behaviour may be interpreted as increased
attractiveness or competitiveness or, more likely, as hastiness and reduced
ability to assess mate quality. Overall, many of the social isolation-induced
behavioural changes in P. persimilis are analogous to those observed in other
animals such as cockroaches, fruit flies, fishes or rodents. We argue that, due
to their profound and persistent effects, early social deprivation or enrichment
may be important determinants in shaping animal personalities.
PMID- 28502988
TI - Testing Differential Networks with Applications to Detecting Gene-by-Gene
Interactions.
AB - Model organisms and human studies have led to increasing empirical evidence that
interactions among genes contribute broadly to genetic variation of complex
traits. In the presence of gene-by-gene interactions, the dimensionality of the
feature space becomes extremely high relative to the sample size. This imposes a
significant methodological challenge in identifying gene-by-gene interactions. In
the present paper, through a Gaussian graphical model framework, we translate the
problem of identifying gene-by-gene interactions associated with a binary trait D
into an inference problem on the difference of two high-dimensional precision
matrices, which summarize the conditional dependence network structures of the
genes. We propose a procedure for testing the differential network globally that
is particularly powerful against sparse alternatives. In addition, a multiple
testing procedure with false discovery rate control is developed to infer the
specific structure of the differential network. Theoretical justification is
provided to ensure the validity of the proposed tests and optimality results are
derived under sparsity assumptions. A simulation study demonstrates that the
proposed tests maintain the desired error rates under the null and have good
power under the alternative. The methods are applied to a breast cancer gene
expression study.
PMID- 28502983
TI - Alkaline phosphatase: a novel treatment target for cardiovascular disease in CKD.
AB - Cardiovascular disease is the main cause of early death in the settings of
chronic kidney disease (CKD), type 2 diabetes mellitus (T2DM), and ageing.
Cardiovascular events can be caused by an imbalance between promoters and
inhibitors of mineralization, which leads to vascular calcification. This process
is akin to skeletal mineralization, which is carefully regulated and in which
isozymes of alkaline phosphatase (ALP) have a crucial role. Four genes encode ALP
isozymes in humans. Intestinal, placental and germ cell ALPs are tissue-specific,
whereas the tissue-nonspecific isozyme of ALP (TNALP) is present in several
tissues, including bone, liver and kidney. TNALP has a pivotal role in bone
calcification. Experimental overexpression of TNALP in the vasculature is
sufficient to induce vascular calcification, cardiac hypertrophy and premature
death, mimicking the cardiovascular phenotype often found in CKD and T2DM.
Intestinal ALP contributes to the gut mucosal defence and intestinal and liver
ALPs might contribute to the acute inflammatory response to endogenous or
pathogenic stimuli. Here we review novel mechanisms that link ALP to vascular
calcification, inflammation, and endothelial dysfunction in kidney and
cardiovascular diseases. We also discuss new drugs that target ALP, which have
the potential to improve cardiovascular outcomes without inhibiting skeletal
mineralization.
PMID- 28502989
TI - A 1024-Channel CMOS Microelectrode Array With 26,400 Electrodes for Recording and
Stimulation of Electrogenic Cells In Vitro.
AB - To advance our understanding of the functioning of neuronal ensembles, systems
are needed to enable simultaneous recording from a large number of individual
neurons at high spatiotemporal resolution and good signal-to-noise ratio.
Moreover, stimulation capability is highly desirable for investigating, for
example, plasticity and learning processes. Here, we present a microelectrode
array (MEA) system on a single CMOS die for in vitro recording and stimulation.
The system incorporates 26,400 platinum electrodes, fabricated by in-house post
processing, over a large sensing area (3.85 * 2.10 mm2) with sub-cellular spatial
resolution (pitch of 17.5 MUm). Owing to an area and power efficient
implementation, we were able to integrate 1024 readout channels on chip to record
extracellular signals from a user-specified selection of electrodes. These
channels feature noise values of 2.4 MUVrms in the action-potential band (300 Hz
10 kHz) and 5.4 MUVrms in the local-field-potential band (1 Hz-300 Hz), and
provide programmable gain (up to 78 dB) to accommodate various biological
preparations. Amplified and filtered signals are digitized by 10 bit parallel
single-slope ADCs at 20 kSamples/s. The system also includes 32 stimulation
units, which can elicit neural spikes through either current or voltage pulses.
The chip consumes only 75 mW in total, which obviates the need of active cooling
even for sensitive cell cultures.
PMID- 28502991
TI - Analysis of Thickness and Quality factor of a Double Paddle Oscillator at Room
Temperature.
AB - In this paper, we evaluate the quality (Q) factor and the resonance frequency of
a double paddle oscillator (DPO) with different thickness using analytical,
computational and experimental methods. The study is carried out for the 2nd anti
symmetric resonance mode that provides extremely high experimental Q factors on
the order of 105. The results show that both the Q factor and the resonance
frequency of a DPO increase with the thickness at room temperature.
PMID- 28502992
TI - Religious Involvement and Health over Time: Predictive Effects in a National
Sample of African Americans.
AB - In this study, two telephone interviews that assessed both religious involvement
and health-related quality of life were conducted approximately 2.5 years apart
in a national sample of 290 African Americans. Religious involvement was assessed
with an instrument that measured both personal religious beliefs (e.g., having a
personal relationship with God) and more public religious behaviors (e.g.,
attending church services). Health-related quality of life was measured with
version 2 of the Medical Outcomes Study 12-item short form (SF-12v2). Structural
equation models indicated that higher religious beliefs at baseline predicted
better physical and mental health 2.5 years later. Higher religious behaviors at
baseline contributed smaller, complementary suppression effects. Physical and
mental health indicators from the SF-12v2 at baseline did not predict changes in
either religious beliefs or religious behaviors over time. These findings
indicate that, for African Americans, personal religious beliefs lead to
beneficial health effects over time, whereas individual differences in health do
not appear to predict changes in religious involvement.
PMID- 28502990
TI - Short Read Mapping: An Algorithmic Tour.
AB - Ultra-high-throughput next-generation sequencing (NGS) technology allows us to
determine the sequence of nucleotides of many millions of DNA molecules in
parallel. Accompanied by a dramatic reduction in cost since its introduction in
2004, NGS technology has provided a new way of addressing a wide range of
biological and biomedical questions, from the study of human genetic disease to
the analysis of gene expression, protein-DNA interactions, and patterns of DNA
methylation. The data generated by NGS instruments comprise huge numbers of very
short DNA sequences, or 'reads', that carry little information by themselves.
These reads therefore have to be pieced together by well-engineered algorithms to
reconstruct biologically meaningful measurments, such as the level of expression
of a gene. To solve this complex, high-dimensional puzzle, reads must be mapped
back to a reference genome to determine their origin Due to sequencing errors and
to genuine differences between the reference genome and the individual being
sequenced, this mapping process must be tolerant of mismatches, insertions, and
deletions. Although optimal alignment algorithms to solve this problem have long
been available, the practical requirements of aligning hundreds of millions of
short reads to the 3 billion base pair long human genome have stimulated the
development of new, more efficient methods, which today are used routinely
throughout the world for the analysis of NGS data.
PMID- 28502993
TI - Mode selection for electrostatic beam resonators based on motional resistance and
quality factor.
AB - An analytical comparison between the fundamental mode and higher modes of
vibration for an electrostatic beam resonator is presented. Multiple mode numbers
can be matched to a desired resonance frequency through appropriate scaling.
Therefore, it is important to determine which mode yields the best performance. A
dynamic model of the resonator is derived and then used to determine the motional
resistance for each mode. The resulting equation provides the basis for comparing
performance between modes using motional resistance and quality factor. As a
demonstration of the approach, a quality factor model that has been previously
validated experimentally is introduced. Numerical results for silicon resonators
indicate that the fundamental mode can provide a lower motional resistance and
higher quality factor when the resonators under comparison have the same aspect
ratio or the same stiffness.
PMID- 28502994
TI - Depoling and fatigue behavior of Pb(Mg1/3Nb2/3)O3-PbTiO3 single crystal at
megahertz frequencies under bipolar electric field.
AB - Bipolar electric field induced degradation in [001]c poled Pb(Mg1/3Nb2/3)O3
0.29PbTiO3 (PMN-0.29PT) single crystals was investigated at megahertz
frequencies. The electromechanical coupling factor kt , dielectric constant
epsilonr , dielectric loss D, and piezoelectric constant d33 were measured as a
function of amplitude, frequency, and number of cycles of the applied electric
field. Our results showed that samples degrade rapidly when the field amplitude
is larger than a critical value due to the onset of domain switching. We define
this critical value as the effective coercive field Ec at high frequencies, which
increases drastically with frequency. We also demonstrate an effective counter
depoling method by using a dc bias, which could help the design of high field
driven devices based on PMN-PT single crystals and operated at megahertz
frequencies.
PMID- 28502995
TI - The Psycho-Lexical Approach in Exploring the Field of Values: A Reply to
Schwartz.
AB - We reply to each of the issues raised by Schwartz in a commentary on our article
on a comparison of value taxonomies. We discuss two approaches, mentioned in that
commentary, the lexical approach and the theory-driven approach, especially with
respect to their capacities in covering the domain of values and with respect to
the representation of important values in a useful structure. We refute the
critique by Schwartz that the lexical approach is superfluous, because his theory
"toward universals in values" would already cover all values, and that their
mutual relationships are relevant to individuals around the globe. We explain the
necessity and strength of the lexical approach in taxonomizing the value domain,
both within and across languages. Furthermore, we argue that principal components
analysis (PCA) and simultaneous component analysis (SCA) are most adequate in
arriving at a satisfactory structuring of the great many values in terms of both
underlying constructs and their facets. We point to a misrepresentation in
Schwartz's circular model, and we review some misunderstandings on the side of
Schwartz with respect to our results in comparison with those proceeding from his
circular model.
PMID- 28502998
TI - Exploring the Dimensionality of Ethnic Minority Adaptation in Britain: An
Analysis across Ethnic and Generational Lines.
AB - In this article I explore the dimensionality of the long-term experiences of the
main ethnic minority groups (their adaptation) in Britain. Using recent British
data, I apply factor analysis to uncover the underlying number of factors behind
variables deemed to be representative of the adaptation experience within the
literature. I then attempt to assess the groupings of adaptation present in the
data, to see whether a typology of adaptation exists (i.e. whether adaptation in
different dimensions can be concomitant with others). The analyses provide an
empirical evidence base to reflect on: (1) the extent of group differences in the
adaptation process, which may cut across ethnic and generational lines; and (2)
whether the uncovered dimensions of adaptation match existing theoretical views
and empirical evidence. Results suggest that adaptation should be regarded as a
multi-dimensional phenomenon where clear typologies of adaptation based on
specific trade-offs (mostly cultural) appear to exist.
PMID- 28502997
TI - Does measurement invariance hold for the official Mexican multidimensional
poverty measure? A state-level analysis 2012.
AB - One of the main goals in poverty measurement is making comparisons of prevalence
and severity across geographical units. This is attained by merely disaggregating
the index in question. The underlying assumption is that comparisons across units
are tenable, inasmuch as the same indicators are utilised for constructing the
index. Nonetheless, in practice, this assumption is very rarely tested. From the
statistical perspective, measurement invariance (MI) must hold for comparisons to
be valid, and violations thereof indicate that a given poverty index measures
different things across different countries, states, counties, etc. Consequently,
differentials in severity and prevalence cannot be attributed exclusively to the
underlying construct (i.e. poverty) but to factors not considered in the measure.
This article tests whether MI holds for two indexes: the Mexican official
multidimensional measure (MPM) and an adjusted multidimensional measure (MPM-A)
that uses less severe thresholds. The analysis is conducted using a novel method
called the 'alignment method'. It uses these two measures and the method as an
illustration of why it is vital to introduce MI tests into poverty measurement.
The results suggest that partial strong MI holds for the official measure and MI
is violated when the thresholds are adjusted. Partial strong MI guarantees making
valid comparisons across the 32 states. Should the official measure requires to
be updated with other thresholds, it would be necessary to adjust the threshold
or drop the indicator for water deprivation.
PMID- 28502996
TI - The Influence of the Aromatic Character in the Gas Chromatography Elution Order:
The Case of Polycyclic Aromatic Hydrocarbons.
AB - A link between the aromatic character of polycyclic aromatic hydrocarbons and gas
chromatography elution order in columns with a polysiloxane backbone in the
stationary phase is reported for the first time. The aromatic character was
calculated using a method that combines the pi-Sextet Rule and the Pauling Ring
Bond Orders to allow the establishment of the location and migration of aromatic
sextets in PAH structures. One GC column with a polysiloxane - like backbone (Rxi
PAH) and three GC columns with a polysiloxane backbone (DB-5, SE-52, and LC-50),
were used for the analysis. According to the results of this study, within an
isomer group, PAHs that contain a lower number of rings affected by the aromatic
sextets tend to elute earlier than PAHs that contain a higher number of rings
affected by the aromatic sextets. The PAHs that follow the calculated elution
order are 88 % in the Rxi-PAH column, 88 % in the DB-5 column, 93 % in the SE-52
column, and 85% in the LC-50 column. It is expected that future analyses with
other aromatic compounds in GC columns with a polysiloxane backbone in the
stationary phase will follow a GC elution order that agrees with the aromatic
character of the molecules.
PMID- 28502999
TI - Legal Origin and Social Solidarity: The Continued Relevance of Durkheim to
Comparative Institutional Analysis.
AB - By using the classic works of Durkheim as a theoretical platform, this research
explores the relationship between legal systems and social solidarity. We found
that certain types of civil law system, most notably those of Scandinavia, are
associated with higher levels of social capital and better welfare state
provision. However, we found the relationship between legal system and societal
outcomes is considerably more complex than suggested by currently fashionable
economistic legal origin approaches, and more in line with the later writings of
Durkheim, and, indeed, the literature on comparative capitalisms. Relative
communitarianism was strongly affected by relative development, reflecting the
complex relationship between institutions, state capabilities and informal social
ties and networks.
PMID- 28503001
TI - Goodness of Fit Tests for Linear Mixed Models.
AB - Linear mixed models (LMMs) are widely used for regression analysis of data that
are assumed to be clustered or correlated. Assessing model fit is important for
valid inference but to date no confirmatory tests are available to assess the
adequacy of the fixed effects part of LMMs against general alternatives. We
therefore propose a class of goodness-of-fit tests for the mean structure of
LMMs. Our test statistic is a quadratic form of the difference between observed
values and the values expected under the estimated model in cells defined by a
partition of the covariate space. We show that this test statistic has an
asymptotic chi-squared distribution when model parameters are estimated by
maximum likelihood or by least squares and method of moments, and study its power
under local alternatives both analytically and in simulations. Data on repeated
measurements of thyroglobulin from individuals exposed to the accident at the
Chernobyl power plant in 1986 are used to illustrate the proposed test.
PMID- 28503000
TI - Enantioselective Dirhodium(II)-Catalyzed Cyclopropanations with
Trimethylsilylethyl and Trichloroethyl Aryldiazoacetates.
AB - Highly functionalized cyclopropanecarboxylates were readily prepared by rhodium
catalyzed cyclopropanation of alkenes with aryldiazoacetates and
styryldiazoaceates, in which the ester functionality is either
trimethylsilylethyl (TMSE) or trichlorethyl (TCE). By having labile protecting
groups on the ester, chiral triarylcyclopropane carboxylate ligands were
conveniently prepared. The asymmetric induction during cyclopropanation is
dependent on the nature of the ester group and the chiral dirhodium
tetracarboxylate catalyst. The prolinate catalyst Rh2(S-DOSP)4 was the optimum
catalyst for asymmetric intermolecular cyclopropanation of TMSE diazoesters with
styrene, while Rh2(R-BPCP)4 was the optimum catalyst for TCE diazoesters.
PMID- 28503002
TI - NEUROPSYCHOLOGICAL FUNCTIONING IN PRISONERS WITH AND WITHOUT SELF-INJURIOUS
BEHAVIORS: Implications for the Criminal Justice System.
AB - Neuropsychological functioning has not yet been investigated among prisoners who
engage in self-injurious behaviors, specifically attempted suicide and
nonsuicidal self-injury (NSSI). The purpose of this study was to investigate
neuropsychological functioning in prisoners with and without histories of NSSI
and attempted suicide. The sample consisted of 173 male prisoners referred for
neuropsychological evaluation. Of participants, 56% reported a history of self
injury. Performance on the neuropsychological domains of intelligence, memory,
attention, motor functioning, and executive functioning was assessed. No group
differences were found among those with NSSI, with NSSI and suicide attempts, and
with no history of deliberate self-harm, although functioning was poor in all
domains. Implications of the high prevalence of self-injury in this prison
sample, as well as implications of impaired functioning on the treatment of self
injurious behaviors, are discussed.
PMID- 28503003
TI - Characterization of moderate ash-and-gas explosions at Santiaguito volcano,
Guatemala, from infrasound waveform inversion and thermal infrared measurements.
AB - The rapid discharge of gas and rock fragments during volcanic eruptions generates
acoustic infrasound. Here we present results from the inversion of infrasound
signals associated with small and moderate gas-and-ash explosions at Santiaguito
volcano, Guatemala, to retrieve the time history of mass eruption rate at the
vent. Acoustic waveform inversion is complemented by analyses of thermal infrared
imagery to constrain the volume and rise dynamics of the eruption plume. Finally,
we combine results from the two methods in order to assess the bulk density of
the erupted mixture, constrain the timing of the transition from a momentum
driven jet to a buoyant plume, and to evaluate the relative volume fractions of
ash and gas during the initial thrust phase. Our results demonstrate that
eruptive plumes associated with small-to-moderate size explosions at Santiaguito
only carry minor fractions of ash, suggesting that these events may not involve
extensive magma fragmentation in the conduit.
PMID- 28503004
TI - Factors controlling the evaporation of secondary organic aerosol from alpha
pinene ozonolysis.
AB - Secondary organic aerosols (SOA) forms a major fraction of organic aerosols in
the atmosphere. Knowledge of SOA properties that affect their dynamics in the
atmosphere is needed for improving climate models. By combining experimental and
modeling techniques, we investigated the factors controlling SOA evaporation
under different humidity conditions. Our experiments support the conclusion of
particle phase diffusivity limiting the evaporation under dry conditions.
Viscosity of particles at dry conditions was estimated to increase several orders
of magnitude during evaporation, up to 109 Pa s. However, at atmospherically
relevant relative humidity and time scales, our results show that diffusion
limitations may have a minor effect on evaporation of the studied alpha-pinene
SOA particles. Based on previous studies and our model simulations, we suggest
that, in warm environments dominated by biogenic emissions, the major uncertainty
in models describing the SOA particle evaporation is related to the volatility of
SOA constituents.
PMID- 28503005
TI - Electron acceleration during streamer collisions in air.
AB - High-voltage laboratory experiments show that discharges in air, generated over a
gap of one meter with maximal voltage of 1 MV, may produce X-rays with photon
energies up to 1 MeV. It has been suggested that the photons are bremsstrahlung
from electrons accelerated by the impulsive, enhanced field during collisions of
negative and a positive streamers. To explore this process, we have conducted the
first self-consistent particle simulations of streamer encounters. Our simulation
model is a 2-D, cylindrically symmetric, particle-in-cell code tracing the
electron dynamics and solving the space charge fields, with a Monte Carlo scheme
accounting for collisions and ionization. We present the electron density, the
electric field, and the velocity distribution as functions of space and time.
Assuming a background electric field 1.5 times the breakdown field, we find that
the electron density reaches 2.1021 m-3, the size of the encounter region is
~3.10-12 m3 and that the field enhances to ~9 times the breakdown field during
~10-11 s. We further find that the radial component becomes comparable to the
parallel component, which together with angular scattering leads to an almost
isotropic distribution of electrons. This is consistent with laboratory
observations that X-rays are emitted isotropically. However, the maximum energy
of electrons reached in the simulation is ~600 eV, which is well below the
energies required to explain observations. The reason is that the encounter
region is small in size and duration. For the photon energies observed, the field
must be enhanced in a larger region and/or for a longer time.
PMID- 28503006
TI - Within-Mother Estimates of the Effects of WIC on Birth Outcomes in New York City.
AB - There is a large literature suggesting that "WIC works" to improve birth
outcomes. However, methodological limitations related to selection into the WIC
program have left room for doubt about this conclusion. This paper uses birth
records from New York City to address some limitations of the previous
literature. We estimate models with mother fixed effects to control for fixed
characteristics of mothers and we directly investigate the way that time-varying
characteristics of mothers affect selection into the WIC program. We find that
WIC is associated with reductions in low birth weight, even among full term
infants, and with reductions in the probability that a child is "small for
dates." These improvements are associated with a reduction in the probability
that the mother gained too little weight during pregnancy. Improvements tend to
be largest for first born children. We also find that women on WIC are more
likely to be diagnosed with chronic conditions, and receive more intensive
medical services, a finding that may reflect improved access to medical care.
PMID- 28503008
TI - A new model order reduction strategy adapted to nonlinear problems in earthquake
engineering.
AB - Earthquake dynamic response analysis of large complex structures, especially in
the presence of nonlinearities, usually turns out to be computationally
expensive. In this paper, the methodical developments of a new model order
reduction strategy (MOR) based on the proper orthogonal decomposition (POD)
method as well as its practical applicability to a realistic building structure
are presented. The seismic performance of the building structure, a medical
complex, is to be improved by means of base isolation realized by frictional
pendulum bearings. According to the new introduced MOR strategy, a set of
deterministic POD modes (transformation matrix) is assembled, which is derived
based on the information of parts of the response history, so-called snapshots,
of the structure under a representative earthquake excitation. Subsequently, this
transformation matrix is utilized to create reduced-order models of the structure
subjected to different earthquake excitations. These sets of nonlinear low-order
representations are now solved in a fractional amount of time in comparison with
the computations of the full (non-reduced) systems. The results demonstrate
accurate approximations of the physical (full) responses by means of this new MOR
strategy if the probable behavior of the structure has already been captured in
the POD snapshots. Copyright (c) 2016 The Authors. Earthquake Engineering &
Structural Dynamics Published by John Wiley & Sons Ltd.
PMID- 28503007
TI - Individual differences in categorical perception of speech: Cue weighting and
executive function.
AB - This study examined individual differences in categorical perception and the use
of multiple acoustic cues in the perception of the stop voicing contrast. Goals
were to investigate whether gradiency of speech perception was related to
listeners' differential sensitivity to acoustic cues and to individual
differences in executive function. The experiment included two speech perception
tasks (visual analogue scaling [VAS] and anticipatory eye movement [AEM])
administered to 30 English-speaking adults in two separate experimental sessions.
Stimuli were a /ta/ to /da/ continuum that systematically varied VOT and f0.
Findings were that some listeners had a more gradient pattern of responses on the
VAS task; the listeners who had a gradient response pattern on the VAS task also
showed more sensitivity to f0 on the AEM task. The patterns were consistent
across individuals tested on two separate occasions. These results suggest that
variability in how categorically listeners perceive speech sounds is consistent
and systematic within individuals.
PMID- 28503009
TI - Performance of Metal and Polymeric O-Ring Seals during Beyond-Design-Basis
Thermal Conditions.
AB - This paper summarizes the small scale thermal exposure test results of the
performance of metallic and polymeric O-ring seals typically used in radioactive
material transportation packages. Five different O-ring materials were evaluated:
Inconel/silver, ethylene-propylene diene monomer (EPDM), polytetrafluoroethylene
(PTFE), silicone, butyl, and Viton. The overall objective of this study is to
provide test data and insights to the performance of these Oring seals when
exposed to beyond-design-basis temperature conditions due to a severe fire. Tests
were conducted using a small-scale stainless steel pressure vessel pressurized
with helium to 2 bar or 5 bar at room temperature. The vessel was then heated in
an electric furnace to temperatures up to 900 degrees C for a pre-determined
period (typically 8 h to 9 h). The pressure drop technique was used to determine
if leakage occurred during thermal exposure. Out of a total of 46 tests
performed, leakage (loss of vessel pressure) was detected in 13 tests.
PMID- 28503010
TI - Viewpoint: Special Issue on Industrial Robot Agility.
PMID- 28503012
TI - Volumetric and calorimetric properties of aqueous ionene solutions.
AB - The volumetric (partial and apparent molar volumes) and calorimetric properties
(apparent heat capacities) of aqueous cationic polyelectrolyte solutions -
ionenes - were studied using the oscillating tube densitometer and differential
scanning calorimeter. The polyion's charge density and the counterion properties
were considered as variables. The special attention was put to evaluate the
contribution of electrostatic and hydrophobic effects to the properties studied.
The contribution of the CH2 group of the polyion's backbone to molar volumes and
heat capacities was estimated. Synergistic effect between polyion and counterions
was found.
PMID- 28503011
TI - When the "Golden Years" Turn Blue: Using the Healthy Aging Literature to
Elucidate Anxious and Depressive Disorders in Older Adulthood.
AB - Current treatments for disorders of emotion, like pathological anxiety, are often
less effective in older adults than in younger adults and have poorly understood
mechanisms, pointing to the need for psychopathology models that better account
for age-related changes in normative emotional functioning and the expression of
disordered emotion. This article describes ways in which the healthy aging and
emotion literature can enhance understanding and treatment of symptoms of anxiety
and depression in later life. We offer recommendations for how to integrate the
healthy aging literatures' theories and findings with psychopathology research
and clinical practice, and highlight opportunities for future research.
PMID- 28503013
TI - To Educate or To Incarcerate: Factors in Disproportionality in School Discipline.
AB - The school-to-prison pipeline describes the process by which school
suspension/expulsion may push adolescents into the justice system
disproportionately based on race/ethnicity, socioeconomic status, and gender. The
current study moves the field forward by analyzing a survey of a diverse sample
of 2,539 students in 10th to 12th grade in Southern California to examine how
demographic, individual, and family factors contribute to disparities in office
referral and suspension/expulsion. African Americans, boys, and students whose
parents had less education were more likely to be suspended/expelled. Higher
levels of student academic preparation for class, hours spent on homework, and
academic aspiration were associated with less school discipline. Findings suggest
that helping students engage in school may be protective against disproportionate
school discipline.
PMID- 28503014
TI - Fathers' Involvement: Correlates and Consequences for Child Socioemotional
Behavior in the United Kingdom.
AB - This study investigated longitudinal relationships between fathers' involvement,
as measured by reading, and child socioemotional behavior between infancy and age
7 in 9,238 intact two-parent families from the U.K. Millennium Cohort Study, a
national cohort of British children born between 2000 and 2002. Once a variety of
covariates and the potential bidirectional nature of relationships were taken
into account, a path model showed that fathers' involvement with their children
in infancy significantly predicted better socioemotional behavior at age 3,
although the relationship was not strong. Fathers' reading with their children
between ages 3 and 7 was not significantly associated with child socioemotional
behavior, but mothers' reading with their children at age 3 was significantly
associated with improved child socioemotional behavior at ages 3 and 5. Results
also suggested that parenting in the 21st-century British context remains fairly
gendered. Both mothers and fathers were more likely to engage in physical
activities with their sons and artistic activities with their daughters. Fathers'
reading was socially patterned in predicted directions.
PMID- 28503015
TI - Development and Pilot Randomized Control Trial of a Drama Program to Enhance Well
being Among Older Adults.
AB - OBJECTIVE: Develop a novel theatre-based program and test its feasibility,
tolerability, and preliminary efficacy for improving empathy/compassion and well
being among older adults. METHOD: Thirteen older adults were randomized to a 6
week Drama Workshop (DW) program or time-equivalent Backstage Pass (BP) control
condition. Pre- and post-treatment measures included empathy, compassion, and
mood scales. Additional post-treatment measures included self-rated change in
empathy/compassion, confidence, and affect. Participants also rated their
mood/affect after each session. RESULTS: The program was successfully completed
and well-liked. No pre-to-post-treatment changes in empathy/compassion or mood
symptoms were found in either group. Compared to BP, DW weekly ratings indicated
higher levels of anxiety and lower happiness; however, the DW program had higher
self-ratings of positive change in self-esteem, confidence, and happiness post
treatment. DISCUSSION: While the DW may not promote empathy/compassion and was
personally challenging during the program, engagement in dramatic exercises and
rehearsing and performing a dramatic piece was seen by participants as a positive
growth experience, as indicated by the post-treatment ratings of enhanced self
esteem, confidence and happiness. Thus, such a program might be useful for
counteracting some of the potential negative aspects of aging, including reduced
self-efficacy due to physical limitations and negative affect due to losses.
PMID- 28503016
TI - Comparison of Dichotomized and Distributional Approaches in Rare Event Clinical
Trial Design: a Fixed Bayesian Design.
AB - This research was motivated by our goal to design an efficient clinical trial to
compare two doses of docosahexaenoic acid supplementation for reducing the rate
of earliest preterm births and/or preterm births. Dichotomizing continuous
gestational age data using a classic binomial distribution will result in a loss
of information and reduced power. A distributional approach is an improved
strategy to retain statistical power from the continuous distribution. However,
appropriate distributions that fit the data properly, particularly in the tails,
must be chosen, especially when the data are skewed. A recent study proposed a
skew-normal method. We propose a three-component normal mixture model and
introduce separate treatment effects at different components of gestational age.
We evaluate operating characteristics of mixture model, beta-binomial model, and
skew-normal model through simulation. We also apply these three methods to data
from two completed clinical trials from the USA and Australia. Finite mixture
models are shown to have favorable properties in preterm births analysis but
minimal benefit for earliest preterm births analysis. Normal models on log
transformed data have the largest bias. Therefore we recommend finite mixture
model for preterm births study. Either finite mixture model or beta-binomial
model is acceptable for earliest preterm births study.
PMID- 28503017
TI - Automatic localization of landmark sets in head CT images with regression forests
for image registration initialization.
AB - Cochlear Implants (CIs) are electrode arrays that are surgically inserted into
the cochlea. Individual contacts stimulate frequency-mapped nerve endings thus
replacing the natural electro-mechanical transduction mechanism. CIs are
programmed post-operatively by audiologists but this is currently done using
behavioral tests without imaging information that permits relating electrode
position to inner ear anatomy. We have recently developed a series of image
processing steps that permit the segmentation of the inner ear anatomy and the
localization of individual contacts. We have proposed a new programming strategy
that uses this information and we have shown in a study with 68 participants that
78% of long term recipients preferred the programming parameters determined with
this new strategy. A limiting factor to the large scale evaluation and deployment
of our technique is the amount of user interaction still required in some of the
steps used in our sequence of image processing algorithms. One such step is the
rough registration of an atlas to target volumes prior to the use of automated
intensity-based algorithms when the target volumes have very different fields of
view and orientations. In this paper we propose a solution to this problem. It
relies on a random forest-based approach to automatically localize a series of
landmarks. Our results obtained from 83 images with 132 registration tasks show
that automatic initialization of an intensity-based algorithm proves to be a
reliable technique to replace the manual step.
PMID- 28503018
TI - Intensive woodland management in the Middle Ages: spatial modelling based on
archival data.
AB - Firewood played an indispensable role in European socio-economic systems from
prehistory until the nineteenth century. Recent research has shown that in
European temperate lowlands the most important management form to produce
firewood was coppicing. In spite of the growing body of research on traditional
woodland management, there remain large gaps in knowledge. Detailed studies of
individual sites or smaller areas have provided a wealth of information on the
methods of medieval coppicing, and at such sites the long-term effects of
coppicing on vegetation structure and composition have also been examined.
However, little is known about the distribution and extent of coppicing at the
landscape scale, and forming a coherent picture of the spatial extent rather than
the management details of coppicing in larger regions remains a challenge. This
paper investigates the distribution and extent of coppice management in Moravia
(eastern Czech Republic, ca. 22,300 km2) in the Late Middle Ages. We created an
extensive database of written sources that contained information on the presence
of coppice woods at the parish level. Subsequently we used the MAXENT algorithm
to create a model of the distribution of coppicing over the entire area. With the
help of wood production and consumption estimates, we also calculated the minimum
area of managed woodland for the study period. Results show that coppicing was
predominant in the lowlands and often occurred at higher elevations as well,
where neither natural conditions nor tree species composition were favourable.
The paper also highlights the potential of spatial models based on archival data
for historical landscape reconstructions.
PMID- 28503019
TI - Sources and methods to reconstruct past masting patterns in European oak species.
AB - The irregular occurrence of good seed years in forest trees is known in many
parts of the world. Mast year frequency in the past few decades can be examined
through field observational studies; however, masting patterns in the more
distant past are equally important in gaining a better understanding of long-term
forest ecology. Past masting patterns can be studied through the examination of
historical written sources. These pose considerable challenges, because data in
them were usually not recorded with the aim of providing information about
masting. Several studies examined masting in the deeper past, however, authors
hardly ever considered the methodological implications of using and combining
various source types. This paper provides a critical overview of the types of
archival written that are available for the reconstruction of past masting
patterns for European oak species and proposes a method to unify and evaluate
different types of data. Available sources cover approximately eight centuries
and can be put into two basic categories: direct observations on the amount of
acorns and references to sums of money received in exchange for access to acorns.
Because archival sources are highly different in origin and quality, the optimal
solution for creating databases for past masting data is a three-point scale:
zero mast, moderate mast, good mast. When larger amounts of data are available in
a unified three-point-scale database, they can be used to test hypotheses about
past masting frequencies, the driving forces of masting or regional masting
patterns.
PMID- 28503021
TI - Validation of tie corroboration and reported alter characteristics among a sample
of young men who have sex with men.
AB - The differences between direct ties (i.e., ties between a respondent and their
nominees) and ties between nominees (indirect) are key to understanding network
structure, yet remain understudied. Within a sample of 175 young men who have sex
with men, we explored the corroboration of sex and drug ties, and factors
associated with corroboration. The majority of instances in which there was no
corroboration for either sex or drug ties was due to one individual not appearing
in another respondent's network. When an individual did appear in another
respondent's network, direct sex and drug ties were corroborated in most cases.
We also found that more indirect sex ties were corroborated than direct sex ties
(95.7% vs. 88.9%), but the reverse was true for indirect versus direct drug ties
(73.1% vs. 84.1%). Strength of relationship and frequency of communication were
both associated with confirmed direct ties, but not with indirect ties. Based on
these findings, we recommend that direct and indirect ties be treated differently
in network analyses.
PMID- 28503020
TI - Circadian rhythm in mRNA expression of the glutathione synthesis gene Gclc is
controlled by peripheral glial clocks in Drosophila melanogaster.
AB - Circadian coordination of metabolism, physiology, and behaviour is found in all
living kingdoms. Clock genes are transcriptional regulators, and their rhythmic
activities generate daily rhythms in clock-controlled genes which result in
cellular and organismal rhythms. Insects provide numerous examples of rhythms in
behaviour and reproduction, but less is known about control of metabolic
processes by circadian clocks in insects. Recent data suggest that several
pathways involved in protecting cells from oxidative stress may be modulated by
the circadian system, including genes involved in glutathione (GSH) biosynthesis.
Specifically, rhythmic expression of the gene encoding the catalytic subunit
(Gclc) of the rate-limiting GSH biosynthetic enzyme was detected in Drosophila
melanogaster heads. The aim of this study was to determine which clocks in the
fly multi-oscillatory circadian system are responsible for Gclc rhythms. Genetic
disruption of tissue-specific clocks in D. melanogaster revealed that
transcriptional rhythms in Gclc mRNA levels occur independently of the central
pacemaker neurons, because these rhythms persisted in heads of behaviourally
arrhythmic flies with a disabled central clock but intact peripheral clocks.
Disrupting the clock specifically in glial cells abolished rhythmic expression of
Gclc, suggesting that glia play an important role in Gclc transcriptional
regulation, which may contribute to maintaining homeostasis in the fly nervous
system.
PMID- 28503022
TI - An Early Years Toolbox for Assessing Early Executive Function, Language, Self
Regulation, and Social Development: Validity, Reliability, and Preliminary Norms.
AB - Several methods of assessing executive function (EF), self-regulation, language
development, and social development in young children have been developed over
previous decades. Yet new technologies make available methods of assessment not
previously considered. In resolving conceptual and pragmatic limitations of
existing tools, the Early Years Toolbox (EYT) offers substantial advantages for
early assessment of language, EF, self-regulation, and social development. In the
current study, results of our large-scale administration of this toolbox to 1,764
preschool and early primary school students indicated very good reliability,
convergent validity with existing measures, and developmental sensitivity.
Results were also suggestive of better capture of children's emerging abilities
relative to comparison measures. Preliminary norms are presented, showing a clear
developmental trajectory across half-year age groups. The accessibility of the
EYT, as well as its advantages over existing measures, offers considerably
enhanced opportunities for objective measurement of young children's abilities to
enable research and educational applications.
PMID- 28503023
TI - Do resource constraints affect lexical processing? Evidence from eye movements.
AB - Human language is massively ambiguous, yet we are generally able to identify the
intended meanings of the sentences we hear and read quickly and accurately. How
we manage and resolve ambiguity incrementally during real-time language
comprehension given our cognitive resources and constraints is a major question
in human cognition. Previous research investigating resource constraints on
lexical ambiguity resolution has yielded conflicting results. Here we present
results from two experiments in which we recorded eye movements to test for
evidence of resource constraints during lexical ambiguity resolution. We embedded
moderately biased homographs in sentences with neutral prior context and either
long or short regions of text before disambiguation to the dominant or
subordinate interpretation. The length of intervening material had no effect on
ease of disambiguation. Instead, we found only a main effect of meaning at
disambiguation, such that disambiguating to the subordinate meaning of the
homograph was more difficult-results consistent with the reordered access model
and contemporary probabilistic models, but inconsistent with the capacity
constrained model.
PMID- 28503024
TI - Remember dax? Relations between children's cross-situational word learning,
memory, and language abilities.
AB - Learning new words is a difficult task. Children are able to resolve the
ambiguity of the task and map words to referents by tracking co-occurrence
probabilities across multiple moments in time, a behavior termed cross
situational word learning (CSWL). Although we observe developments in CSWL
abilities across childhood, the cognitive processes that drive individual and
developmental change have yet to be identified. This research tested a
developmental systems account by examining whether multiple cognitive systems co
contribute to children's CSWL. The results of two experiments revealed that
multiple cognitive domains, such as memory and language abilities, are likely to
drive the development of CSWL above and beyond children's age. The results also
revealed that memory abilities are likely to be particularly important above and
beyond other cognitive abilities. These findings have implications for theories
and computational models of CSWL, which typically do not account for individual
children's cognitive capacities or changes in cognitive capacities across time.
PMID- 28503025
TI - Gait Speed and Confidence Levels in Persons Using 1 and 2 Canes While Walking a 4
m Course.
AB - This is the first article that the researcher is aware of that compares walking
speed and confidence levels with 1 cane versus 2 canes. An observational study
was conducted with 30 participants who had difficulty walking. Gait speed was
assessed on a 4-m course with the participants using 1 cane, then 2 canes. Of 30
participants, 28 walked faster and demonstrated improved confidence with 2 canes.
Use of 2 canes with gait might be a technique that people want to consider to
improve confidence or to improve walking speed, or improve both.
PMID- 28503027
TI - Introduction to Special Issue: Muslim Cosmopolitanism: Movement, Identity, and
Contemporary Reconfigurations.
PMID- 28503028
TI - The Unintentional Procrastination Scale.
AB - Procrastination refers to the delay or postponement of a task or decision and is
often conceptualised as a failure of self-regulation. Recent research has
suggested that procrastination could be delineated into two domains: intentional
and unintentional. In this two-study paper, we aimed to develop a measure of
unintentional procrastination (named the Unintentional Procrastination Scale or
the 'UPS') and test whether this would be a stronger marker of psychopathology
than intentional and general procrastination. In Study 1, a community sample of
139 participants completed a questionnaire that consisted of several items
pertaining to unintentional procrastination that had been derived from theory,
previous research, and clinical experience. Responses were subjected to a
principle components analysis and assessment of internal consistency. In Study 2,
a community sample of 155 participants completed the newly developed scale, along
with measures of general and intentional procrastination, metacognitions about
procrastination, and negative affect. Data from the UPS were subjected to
confirmatory factor analysis and revised accordingly. The UPS was then validated
using correlation and regression analyses. The six-item UPS possesses construct
and divergent validity and good internal consistency. The UPS appears to be a
stronger marker of psychopathology than the pre-existing measures of
procrastination used in this study. Results from the regression models suggest
that both negative affect and metacognitions about procrastination differentiate
between general, intentional, and unintentional procrastination. The UPS is
brief, has good psychometric properties, and has strong associations with
negative affect, suggesting it has value as a research and clinical tool.
PMID- 28503026
TI - A Cognitive-Behavioral Approach to Case Formulations for Nonsuicidal Self-Injury.
AB - Nonsuicidal self-injury (NSSI) is a highly prevalent behavior among clinical and
nonclinical samples. Despite the prevalence, maladaptive, and potentially
dangerous nature of the behavior, no empirically supported interventions have
been identified specifically for NSSI, and clinicians report a lack of knowledge
regarding the treatment of NSSI. This article discusses the application of a
common component of therapy, the case formulation, to conceptualizing and
treating NSSI. This strategy for case formulation incorporates cognitive
behavioral and functional analytic approaches while focusing on factors pertinent
to the development, maintenance, and treatment of NSSI. A case example is
presented.
PMID- 28503029
TI - Metal Ion-Responsive Fluorescent Probes for Two-Photon Excitation Microscopy.
AB - Metal ion-responsive fluorescent probes are powerful tools for visualizing labile
metal ion pools in live cells. To take full advantage of the benefits offered by
two-photon excitation microscopy, including increased depth penetration, reduced
phototoxicity, and intrinsic 3D capabilities, the photophysical properties of the
probes must be optimized for nonlinear excitation. This review summarizes the
challenges associated with the design of two-photon excitable fluorescent probes
and labels and offers an overview on recent efforts in developing selective and
sensitive reagents for the detection of metal ions in biological systems.
PMID- 28503030
TI - Ligand-Induced Shape Transformation of PbSe Nanocrystals.
AB - We present a study of the relation between the surface chemistry and nanocrystal
shape of PbSe nanocrystals with a variable Pb-to-Se stoichiometry and density of
oleate ligands. The oleate ligand density and binding configuration are monitored
by nuclear magnetic resonance and Fourier transform infrared absorbance
spectroscopy, allowing us to quantify the number of surface-attached ligands per
NC and the nature of the surface-Pb-oleate configuration. The three-dimensional
shape of the PbSe nanocrystals is obtained from high-angle annular dark field
scanning transmission electron microscopy combined with an atom counting method.
We show that the enhanced oleate capping results in a stabilization and extension
of the {111} facets, and a crystal shape transformation from a truncated nanocube
to a truncated octahedron.
PMID- 28503031
TI - Re-interpreting: Narratives of childhood language brokering over time.
AB - This article probes how childhood experiences are actively taken into adult lives
and thus challenges the unwitting and unintentional reproduction of an adult
child binary in childhood studies. We do this by analyzing interviews with one
adult daughter of immigrants from Mexico to the United States at four points in
time (ages 19, 26, 27, and 33). Using narrative analysis to examine the
mutability of memory, we consider how Eva oriented herself to her childhood
story, what was salient and invisible in each recount, the values she associated
with the practice, and the meanings she took from her experiences. We show how
Eva re-interpreted her experiences as an immigrant child language broker in
relation to unfolding life events, showing her childhood to be very much alive in
her adult life. Language brokering serves as one way in which to examine the
interpenetration of childhood into adulthood, rather than being the focus per se.
PMID- 28503032
TI - Limestone and Silica Powder Replacements for Cement: Early-Age Performance.
AB - Developing functional concrete mixtures with less ordinary portland cement (OPC)
has been one of the key objectives of the 21st century sustainability movement.
While the supplies of many alternatives to OPC (such as fly ash or slag) may be
limited, those of limestone and silica powders produced by crushing rocks seem
virtually endless. The present study examines the chemical and physical
influences of these powders on the rheology, hydration, and setting of cement
based materials via experiments and three-dimensional microstructural modeling.
It is shown that both limestone and silica particle surfaces are active templates
(sites) for the nucleation and growth of cement hydration products, while the
limestone itself is also somewhat soluble, leading to the formation of
carboaluminate hydration products. Because the filler particles are incorporated
as active members of the percolated backbone that constitutes initial setting of
a cement-based system, replacements of up to 50 % of the OPC by either of these
powders on a volumetric basis have minimal impact on the initial setting time,
and even a paste with only 5 % OPC and 95 % limestone powder by volume achieves
initial set within 24 h. While their influence on setting is similar, the
limestone and silica powders produce pastes with quite different rheological
properties, when substituted at the same volume level. When proceeding from
setting to later age strength development, one must also consider the dilution of
the system due to cement removal, along with the solubility/reactivity of the
filler. However, for applications where controlled (prompt) setting is more
critical than developing high strengths, such as mortar tile adhesives, grouts,
and renderings, significant levels of these powder replacements for cement can
serve as sustainable, functional alternatives to the oft-employed 100 % OPC
products.
PMID- 28503033
TI - 15-Deoxy-Delta12,14-prostaglandin J2 Exerts Antioxidant Effects While
Exacerbating Inflammation in Mice Subjected to Ureteral Obstruction.
AB - Urinary obstruction is associated with inflammation and oxidative stress, leading
to renal dysfunction. Previous studies have shown that 15-deoxy-Delta12,14
prostaglandin J2 (15d-PGJ2) has both antioxidant and anti-inflammatory effects.
Using a unilateral ureteral obstruction (UUO) mouse model, we examined the
effects of 15d-PGJ2 on oxidative stress and inflammation in the kidney. Mice were
subjected to UUO for 3 days and treated with 15d-PGJ2. Protein and RNA expression
were examined using immunoblotting and qPCR. 15d-PGJ2 increased NF-E2-related
nuclear factor erythroid-2 (Nrf2) protein expression in response to UUO, and heme
oxygenase 1 (HO-1), a downstream target of Nrf2, was induced by 15d-PGJ2.
Additionally, 15d-PGJ2 prevented protein carbonylation, a UUO-induced oxidative
stress marker. Inflammation, measured by nuclear NF-kappaB, F4/80, and MCP-1, was
increased in response to UUO and further increased by 15d-PGJ2. Renal injury was
aggravated by 15d-PGJ2 treatment as measured by kidney injury molecule-1 (KIM-1)
and cortical caspase 3 content. No effect of 15d-PGJ2 was observed on renal
function in mice subjected to UUO. This study illustrates differentiated
functioning of 15d-PGJ2 on inflammation and oxidative stress in response to
obstructive nephropathy. High concentrations of 15d-PGJ2 protects against
oxidative stress during 3-day UUO in mice; however, it aggravates the associated
inflammation.
PMID- 28503034
TI - Is Postpartum Depression a Disease of Modern Civilization?
AB - Access to calorie-dense foods, medicine, and other comforts has made modern
humans healthier than our prehistoric ancestors in many respects. However, the
epidemics of obesity, diabetes, and cardiovascular disease suggest that there are
also drawbacks to modern living. Here, we address the question of whether the
dramatic cultural changes that have occurred over the past century have inflated
rates of postpartum depression, adding postpartum depression to the list of
"diseases of modern civilization." We review evidence from cross-cultural,
epidemiological, and experimental studies documenting associations between
postpartum depression and modern patterns of early weaning, diets deficient in
essential fatty acids, low levels of physical activity, low levels of sun
exposure, and isolation from kin support networks, all of which mark significant
divergences from lifestyles believed to have been typical throughout human
evolutionary history. This "mismatch hypothesis" of postpartum depression
integrates research across diverse research areas and generates novel
predictions.
PMID- 28503035
TI - Current Trends in Canine Problem-Solving and Cognition.
AB - Dogs have occupied a central place in modern comparative cognition, partly
because of their specific past and present relationship with humans. Over the
years, we have gained insights about the functioning of the dog's mind, which has
helped us to understand how dogs' problem-solving abilities differ from those
present in related species such as the wolf. Novel methodologies are also
emerging that allow for the study of neural and genetic mechanisms that control
mental functions. By providing an overview from an ethological perspective, we
call for greater integration of the field and a better understanding of natural
dog behavior as a way to generate scientific hypotheses.
PMID- 28503037
TI - Conference Editorial.
PMID- 28503036
TI - Clinico-radiological evaluation of retear rate in arthroscopic double row versus
single row repair technique in full thickness rotator cuff tear.
AB - BACKGROUND: Rotator cuff tear is most troublesome issue in shoulder surgery.
Retear is seen in arthroscopically repaired rotator cuff tear. PURPOSE: The
functional outcome and retear rate in primary full thickness rotator cuff tear
operated by single and double row repair technique. METHODS: 56 cases with full
thickness tear of rotator cuff operated by single or double (28 each) were
studied. Retear rate is evaluated after at least 6 months after surgery. RESULTS:
There was a statistical difference in retear rate between double row and single
row repair (p value <0.01). CONCLUSION: Retear rate is low in double row repair
technique.
PMID- 28503038
TI - IAPCON 2017 Proceedings.
PMID- 28503040
TI - Recommendations to Support Nurses and Improve the Delivery of Oncology and
Palliative Care in India.
AB - CONTEXT: Nurses in India often practice in resource-constrained settings and care
for cancer patients with high symptom burden yet receive little oncology or
palliative care training. AIM: The aim of this study is to explore challenges
encountered by nurses in India and offer recommendations to improve the delivery
of oncology and palliative care. METHODS: Qualitative ethnography. SETTING: The
study was conducted at a government cancer hospital in urban South India. SAMPLE:
Thirty-seven oncology/palliative care nurses and 22 others (physicians, social
workers, pharmacists, patients/family members) who interact closely with nurses
were included in the study. DATA COLLECTION: Data were collected over 9 months
(September 2011- June 2012). Key data sources included over 400 hours of
participant observation and 54 audio-recorded semi-structured interviews.
ANALYSIS: Systematic qualitative analysis of field notes and interview
transcripts identified key themes and patterns. RESULTS: Key concerns of nurses
included safety related to chemotherapy administration, workload and clerical
responsibilities, patients who died on the wards, monitoring family attendants,
and lack of supplies. Many participants verbalized distress that they received no
formal oncology training. CONCLUSIONS: Recommendations to support nurses in India
include: prioritize safety, optimize role of the nurse and explore innovative
models of care delivery, empower staff nurses, strengthen nurse leadership, offer
relevant educational programs, enhance teamwork, improve cancer pain management,
and engage in research and quality improvement projects. Strong institutional
commitment and leadership are required to implement interventions to support
nurses. Successful interventions must account for existing cultural and
professional norms and first address safety needs of nurses. Positive aspects
from existing models of care delivery can be adapted and integrated into general
nursing practice.
PMID- 28503039
TI - The Possible Role of Meditation in Myofascial Pain Syndrome: A New Hypothesis.
AB - BACKGROUND OF HYPOTHESIS: Myofascial pain syndrome (MPS) is the most common
musculoskeletal pain disorder of the head and neck area. In the past, several
theories were put forth to explain its origin and nature, but none proved
complete. Myofascial pain responds to changing psychological states and stress,
anxiety, lack of sleep, anger, depression and chronic pain are direct
contributional factors. Myofascial pain syndrome may be considered as a
psychosomatic disorder. There are numerous accepted palliative approaches, but of
all, relaxation techniques stand out and initiate healing at the base level. In
this article, the connection between mental factors, MPS and meditation are
highlighted. Recent literature has shed light on the fundamental role of free
radicals in the emergence of myofascial pain. The accumulating free radicals
disrupt mitochondrial integrity and function, leading to sustenance and
progression of MPS. Meditation on the other hand was shown to reduce free radical
load and can result in clinical improvement. 'Mindfulness' is the working
principle behind the effect of all meditations, and I emphasize that it can serve
as a potential tool to reverse the neuro-architectural, neurobiological and
cellular changes that occur in MPS. CONCLUSIONS: The findings described in this
paper were drawn from studies on myofascial pain, fibromyalgia, similar chronic
pain models and most importantly from self experience (experimentation). Till
date, no hypothesis is available connecting MPS and meditation. Mechanisms
linking MPS and meditation were identified, and this paper can ignite novel
research in this direction.
PMID- 28503041
TI - Pediatric End-of-life Care Barriers and Facilitators: Perception of Nursing
Professionals in Jordan.
AB - INTRODUCTION: End-of-life care is a critical issue for pediatric population with
terminal illness to ensure the best possible quality of care for them and their
families. A survey was conducted to identify the barriers and facilitators to
provide pediatric end-of-life care. METHODS: A descriptive cross-sectional study
was conducted at three tertiary centers providing end-of-life care in Jordan. Two
hundred critical care nurses were surveyed (response rate 93%). RESULTS: Nurses
reported moderate level of experience in all areas of delivering pediatric end-of
life care. The highest scoring of barriers respectively were patients-families
barriers having deal with angry family member; health-care professional barriers
multiple physicians, involved with one patient, who differ in opinion about the
direction care, and where plan of care should go; and organizational barriers not
available support person for the family. The highest scoring of facilitators
respectively were of patients families facilitators having family members accept
that the patient is dying; health-care professional-facilitators having a
physician agrees about the direction of care, and organizational facilitators
providing family members adequate time to be alone with the pediatric after he or
she has died. CONCLUSION: Nurses perceived that patient-family, health-care
professionals, and organizational related barriers and facilitators were had the
most influence in providing of pediatric end-of-life care. Findings highlighted
the need for additional education and support for pediatric staff, across
professions, in providing pediatric end-of-life care. A pediatric end-of-life
care team should be developed to assist in improving patients' quality of care
and increasing the awareness for the need for a standardized tool to evaluate the
nursing competency level concerning pediatric end-of-life care.
PMID- 28503042
TI - Assessment of Cancer-related Fatigue among Cancer Patients Receiving Various
Therapies: A Cross-sectional Observational Study.
AB - OBJECTIVE: The objective of this cross-sectional, noninterventional 3-month
observational study was to analyze the prevalence of the cancer-related fatigue
(CRF) in cancer patient populations with correlation of CRF with different
treatment modalities. MATERIALS AND METHODS: A descriptive study was carried out
jointly by the pharmacology and oncology departments of a tertiary care center in
the Malwa region of Punjab. The data collection was performed by administering
the validated Brief Fatigue Inventory (BFI) after obtaining the informed consent.
RESULTS: One hundred and twenty-six cancer patients were recruited with the mean
age of 49.13 years +/- 14.35 (standard deviation). There are statistical
correlations found between fatigue and chemotherapy agents such as vinblastine,
dacarbazine, and cyclophosphamide. CONCLUSION: We observed that CRF is a symptom
that is experienced by majority of cancer patients, irrespective of the
diagnosis, or type of treatment received. In addition, assessing CRF before and
after treatment will facilitate health-care practitioner to treat this symptom.
PMID- 28503044
TI - Erratum: Impact of Scrambler Therapy on Pain Management and Quality of Life in
Cancer Patients: A Study of Twenty Cases.
AB - [This corrects the article on p. 18 in vol. 23, PMID: 28216858.].
PMID- 28503043
TI - Integration of Specialized Pain Control Services in Palliative Care: A Nationwide
Web-based Survey.
AB - INTRODUCTION: Pain control is an important part of palliative care (PC), and
conventional analgesics do not provide adequate pain relief to all patients. Many
patients present with complex pain syndromes that require interventional pain
control measures usually deployed by pain specialists. There is adequate
integration of specialized pain control services with PC elsewhere, but
information about the same in our country is lacking. MATERIALS AND METHODS: An
internet survey was conducted among palliative specialists regarding the need and
availability of pain specialists for their patients suffering from complex pain
syndromes. Their attitude toward integrating specialized pain control services in
their practice was also explored. RESULTS: Majority of palliative physicians came
across situations where specialists in pain would control the patients' pain
better. There was a poor availability of such services, and when available, the
cost was significant. It is heartening to note that though there is poor
integration of specialized pain control services with palliation, palliative
physicians acknowledge the need for pain specialists and their techniques for
providing pain relief for their patients. CONCLUSIONS: Effective pain control is
needed in palliation, barriers however exist, and there is a need to make pain
specialists and interventional techniques more freely available.
PMID- 28503045
TI - Review of Angiotensin-converting Enzyme Inhibitory Assay: Rapid Method in Drug
Discovery of Herbal Plants.
AB - The renin-angiotensin-aldosterone system is a signaling pathway which responsible
in the blood pressure regulation. Angiotensin-converting enzyme (ACE) is one of
the key elements responsible for the hypertensive mechanism. It converts
angiotensin-I to angiotensin-II. The discovery history of the ACE inhibitory
activity assay method has been through a long stage for decades and development
continues until today. The ACE inhibitory activity has become an effective
screening method in the search for new antihypertensive agents from herbal
plants. Some of in vitro assay methods were used to examine the activity of ACE
inhibitors based on the substrate usage, such as; Cushman and Cheung Method using
a substrate hippuryl-histidyl-leucine (HHL), Holmquist method using a substrate
furanacryloyl-tripeptide, Elbl and Wagner method using a substrate benzoil-[l
14C] glicyl-L-histidine-L-leucine, Carmel and Yaron method using a substrate o
aminobenzoylglycyl-p-nitrophenylalanilproline, and Lam method using 3
hydroxybutyrylglycyl-glycyl-glycine as substrate. Several different methods to
measure the results of enzymatic reactions or separating substrate with products,
including spectrophotometric, fluorometric, high-performance liquid
chromatography, electrophoresis, and radiochemistry. Application of the test
method for screening the ACE inhibitors activity and investigation of active
compounds from natural products can be done easily with this method, it is very
helpful in research because the results obtained are simple, accurate, and rapid.
PMID- 28503046
TI - Reflections about Osteoarthritis and Curcuma longa.
AB - Osteoarthritis (OA) is a chronic inflammatory degenerative process that affects
joints such as the hands, hips, shoulders, feet, spine, and especially knees in
millions of people worldwide. Some authors have shown that Curcuma longa
components may exhibit benefic effects in the treatment of degenerative diseases
as OA. This plant belongs to the family Zingiberaceae and it is popularly known
as turmeric or saffron. This review intended to perform a retrospective search to
identify studies involving humans and animal models. This review was based on
articles linking OA and C. longa. Databases as Medline, Science Direct, and
Lilacs were consulted and a retrospective search was carried out in order to
identify studies involving humans and animal models. The curcuminoids from C.
longa exhibit actions at different locations in the pathogenesis of OA once it
may play an important role as anti-inflammatory, down-regulating enzymes as
phospholipase A2, cyclooxygenase-2, and lipoxygenases, and reducing tumor
necrosis factor-alpha-and interleukins such as interleukin-1beta (IL-1beta), IL
6, and IL-8. They also act as inducer of apoptosis in synoviocytes, decreasing
the inflammation process and may also reduce the synthesis of reactive oxygen
species. For these reasons, new pharmaceutical technology and pharmacological
studies should be proposed to determine the dose, the best delivery vehicle,
pharmaceutical formulation and route of administration of this plant so its use
as an adjunct in the treatment of OA may become a reality in clinical practice.
PMID- 28503048
TI - Antifertility Effect of Bougainvillea spectabilis or Paper Flower.
AB - Bougainvillea spectabilis (Family: Nyctaginaceae), commonly referred to as Great
Bougainvillea or Paper Flower, is one of the traditional medicinal plants with
potential antifertility activity. The aqueous extract and decoction of this plant
have been used as fertility control among the tribal people in many countries.
Furthermore, it has been shown to possess anticancer, antidiabetic,
antihepatotoxic, anti-inflammatory, antihyperlipidemic, antimicrobial,
antioxidant, and antiulcer properties. Its phytoconstituents such as alkaloids,
essential oils, flavonoids, glycosides, oxalates, phenolics, phlobotannins,
quinones, saponins, tannins, and terpenoids were reported as the basis of its
efficacious therapeutic properties. The other important constituents which
contribute to the remedial properties are bougainvinones, pinitol, quercetagetin,
quercetin, and terpinolene. Published information on the antifertility property
of B. spectabilis was gathered by the use of different database platforms
including Google Scholar, ScienceDirect, PubMed, SciFinder, and Scopus. These
database platforms were used to provide an up-to-date review on its importance.
PMID- 28503047
TI - An Updated Phytopharmacological Review on Medicinal Plant of Arab Region: Apium
graveolens Linn.
AB - Apium graveolens Linn. (Karafs) is used in traditional medicine for the treatment
of the various ailments. There is a need to explore and authenticate the
pharmacological profile and medicinal importance of the Karafs. In this paper,
the literature and the published work on Apium were collected using online
resources "Google scholar", "Web of science", "Scopus" and "PubMed". Each of the
pharmacological activity was searched individually using the keywords
"Apium/Karafs/Apium graveolens + individual pharmacological activity". We
documented the most cited and most recent literatures. The current findings
illuminate the importance Karafs in the traditional medicine and their impact in
treating various diseases. This review strongly supports the fact that the Apium
has emerged as a good source of medicine in treating various diseases. There is
also a need to isolate the bioactive phytochemicals present in this plant.
PMID- 28503049
TI - Current Understanding of Antiobesity Property of Capsaicin.
AB - The capsaicin is an ingredient that we normally mix in food in many cultural
cuisines even in fresh and dried production. Because of its anticancer,
anticholesterolemic, antidiabetic, antihypertensive, anti-inflammatory,
antimicrobial, and antioxidant properties, capsaicin is used worldwide. Moreover,
capsaicin is also used for the protection of cardiovascular and hepatic diseases.
The electronic databases PubMed, Scopus, Web of Science, Google Scholar, and
ScienceDirect were searched since 2000 to present for antiobesity term. This
review article is provided the update information about the antiobesity property
and mechanism of capsaicin for further researches.
PMID- 28503050
TI - Fingerroot, Boesenbergia rotunda and its Aphrodisiac Activity.
AB - Boesenbergia rotunda (Family: Zingiberaceae) as known as fingerroot is a daily
food ingredient and traditional medicinal plant in Southeast Asia and Indo-China.
It has been shown to possess anti-allergic, antibacterial, anticancer, anti
inflammatory, antioxidant, and antiulcer activities and also shown wound healing.
Its common phytochemical components include alkaloids, essential oils,
flavonoids, and phenolics. This plant is rich in boesenbergin, krachaizin,
panduratin, and pinostrobin, all of which has been reported to contribute to its
remedial properties including aphrodisiac property. Based on established
literature on the aphrodisiac property of B. rotunda and possible mode of action,
this review article has attempted to compile that B. rotunda could be further
explored for the development of potential aphrodisiac treatment.
PMID- 28503051
TI - An Update Review on the Anthelmintic Activity of Bitter Gourd, Momordica
charantia.
AB - Momordica charantia (Family: Cucurbitales), as known as bitter melon or gourd, is
a daily consumption as food and traditional medicinal plant in Southeast Asia and
Indo-China. It has been shown to possess anticancer, antidepressant,
antidiabetic, anti-inflammatory, antimicrobial, antiobesity, antioxidant, and
antiulcer properties. Its common phytochemical components include alkaloids,
charantin, flavonoids, glycosides, phenolics, tannins, and terpenoids. This plant
is rich in various saponins including momordicin, momordin, momordicoside,
karavilagenin, karaviloside, and kuguacin, all of which have been reported to
contribute to its remedial properties including antibacterial, antifungal,
antiviral, and antiparasitic infections. Based on established literature on the
anthelmintic activity of M. charantia and possible mode of action, this review
article has attempted to compile M. charantia could be further explored for the
development of potential anthelmintic drug.
PMID- 28503052
TI - Wound Healing Property Review of Siam Weed, Chromolaena odorata.
AB - Chromolaena odorata (Family: Asteraceae) synonyms as Eupatorium odoratum is a
traditional medicinal plant that is widely used for its wound healing property.
In particular, the several parts of this herb have been used to treat wounds,
burns, and skin infections. Furthermore, it has also been shown to possess
anticancer, antidiabetic, anti-hepatotoxic, anti-inflammatory, antimicrobial, and
antioxidant properties. Its phytochemical components are alkaloids, flavonoids,
flavanone, essential oils, phenolics, saponins, tannins, and terpenoids. The
other important constituents of this plant are Eupolin, chromomoric acid,
quercetagetin, and quercetin, all of which contribute to its remedial properties.
Published information on the wound healing property of C. odorata was gathered by
the use of different scientific websites such as Google Scholar, Science Direct,
PubMed, and Web of Knowledge to provide an up-to-date review showing its
importance.
PMID- 28503053
TI - Pea, Pisum sativum, and Its Anticancer Activity.
AB - Pisum sativum (Family: Fabaceae), as known as green pea or garden pea, has long
been important in diet due to its content of fiber, protein, starch, trace
elements, and many phytochemical substances. It has been shown to possess
antibacterial, antidiabetic, antifungal, anti-inflammatory,
antihypercholesterolemia, and antioxidant activities and also shown anticancer
property. Its nonnutritive biologically active components include alkaloids,
flavonoids, glycosides, isoflavones, phenols, phytosterols, phytic acid, protease
inhibitors, saponins, and tannins. This plant is rich in apigenin,
hydroxybenzoic, hydroxycinnamic, luteolin, and quercetin, all of which have been
reported to contribute to its remedial properties including anticarcinogenesis
property. Based on established literature on the anticancer property of P.
sativum and possible mode of action, this review article has focused to
demonstrate that P. sativum could be further explored for the development of
anticancer treatment.
PMID- 28503054
TI - A Review on the Pharmacological Activities and Phytochemicals of Alpinia
officinarum (Galangal) Extracts Derived from Bioassay-Guided Fractionation and
Isolation.
AB - The rhizomes of Alpinia officinarum Hance have been used conventionally for the
treatment of various ailments, triggering a wide interest from the scientific
research community on this ethnomedicinal plant. This review summarizes the
phytochemical and pharmacological properties of the extracts and fractions from
A. officinarum, a plant species of the Zingiberaceae family. Different parts of
the plant - leaves, roots, rhizomes, and aerial parts - have been extracted in
various solvents - methanol, ethanol, ethyl acetate, hexane, dichloromethane,
aqueous, chloroform, and petroleum ether, using various techniques - Soxhlet
extraction, maceration, ultrasonication, and soaking, whereas fractionation of
the plant extracts involves the solvent-solvent partition method. The extracts,
fractions, and isolated compounds have been studied for their biological
activities - antioxidant, antibacterial, anti-inflammatory, anticancer,
antiproliferative, inhibition of enzymes, as well as the inhibition of nitric
oxide production. More findings on A. officinarum are certainly important to
further develop potential bioactive drug compounds.
PMID- 28503056
TI - Energy Level Tuning of Poly(phenylene-alt-dithienobenzothiadiazole)s for Low
Photon Energy Loss Solar Cells.
AB - Six poly(phenylene-alt-dithienobenzothiadiazole)-based polymers have been
synthesized for application in polymer-fullerene solar cells. Hydrogen, fluorine,
or nitrile substitution on benzo-thiadiazole and alkoxy or ester substitution on
the phenylene moiety are investigated to reduce the energy loss per converted
photon. Power conversion efficiencies (PCEs) up to 6.6% have been obtained. The
best performance is found for the polymer-fullerene combination with distinct
phase separation and crystalline domains. This improves the maximum external
quantum efficiency for charge formation and collection to 66%. The resulting
higher photocurrent compensates for the relatively large energy loss per photon
(Eloss = 0.97 eV) in achieving a high PCE. By contrast, the poly-mer that
provides a reduced energy loss (Eloss = 0.49 eV) gives a lower photocurrent and a
reduced PCE of 1.8% because the external quantum efficiency of 17% is limited by
a suboptimal morphology and a reduced driving force for charge transfer.
PMID- 28503057
TI - A new bound for the spectral radius of nonnegative tensors.
AB - By estimating the ratio of the smallest component and the largest component of a
Perron vector, we provide a new bound for the spectral radius of a nonnegative
tensor. And it is proved that the proposed result improves the bound in (Li and
Ng in Numer. Math. 130(2):315-335, 2015).
PMID- 28503058
TI - Academic Testing Accommodations for ADHD: Do They Help?
AB - This study investigated the effectiveness of five commonly administered academic
testing accommodations on reading and math performance in children with attention
deficit hyperactivity disorder (ADHD). A total of 96 parents of 3rd-8th grade
students with ADHD participated. More than half of the sample also had parent
reported learning difficulties in reading and/or math. Individually administered
cognitive and achievement test scores, types of testing accommodations received,
and Maryland School Assessment (MSA) reading and math scores were obtained from
these students' school records. Taking into account grade level and co-occurring
learning difficulties, none of the five accommodations investigated were
associated with better MSA scores among students with ADHD who received the
accommodations versus comparable students who did not. Additionally, individual
variation in processing speed performance did not moderate the association
between receipt of accommodations and reading or math performance. Common testing
accommodations, as presently administered, may offer little benefit for students
with ADHD, regardless of co-occurring learning difficulties.
PMID- 28503055
TI - Protein Markers Associated with an ALDH Sub-Population in Colorectal Cancer.
AB - ALDH has been shown to be a marker that denotes a sub-population of cancer stem
cells in colorectal and other cancers. This sub-population of cells shows an
increased risk for tumor initiation, metastasis, and resistance to chemotherapy
and radiation resulting in recurrence and death. It is thus essential to identify
the important signaling pathways related to ALDH1+ CSCs in colon cancer. The
essential issue becomes to isolate pure sub-populations of cells from
heterogeneous tissues for further analysis. To achieve this goal, tissues from
colorectal cancer Stage III patients were immuno-stained with ALDH1 antibody.
Target ALDH1+ and ALDH1- cells from the same tissue were micro-dissected using
Laser Capture Microdissection (LCM). Captured cells were lysed and analyzed using
LC-MS/MS where around 20,000 cells were available for analysis. This analysis
resulted in 134 proteins which were differentially expressed between ALDH1+ and
ALDH1- cells in three patient sample pairs. Based on these differentially
expressed proteins an IPA pathway analysis was performed that showed two key
pathways in cell to cell signaling and organismal injury and abnormalities. The
IPA analysis revealed beta-catenin, NFkappaB (p65) and TGFbeta1 as important
cancer-related proteins in these pathways. A TMA validation using
immunofluorescence staining of tissue micro-arrays including 170 cases was used
to verify that these key proteins were highly overexpressed in ALDH1+ cells in
colon cancer tissues compared to ALDH1- cells.
PMID- 28503059
TI - Developing effective interorganizational relationships between community
corrections and community treatment providers.
AB - Weak service coordination between community corrections and community treatment
agencies is a significant barrier in the diffusion of pharmacotherapy for
treating opioid and alcohol use disorders. This analysis draws on qualitative
interviews (n=141) collected in a multisite randomized trial to explore what
probation/parole officers and treatment staff believe are the most critical
influences on developing positive interorganizational relationships (IORs)
between their respective agencies. Officers and treatment staff highlighted
factors at both the individual and organizational level, with issues related to
communication surfacing as pivotal. Findings suggest that future interventions
consider developing shared interagency goals with input at all staff levels.
PMID- 28503060
TI - Feasibility and Effectiveness of Parent-Child Interaction Therapy with Victims of
Domestic Violence: A Pilot Study.
AB - Parent-Child Interaction Therapy (PCIT) is an evidence-based treatment for young
children (aged 2.5 to 7 years) with externalizing behavior problems. Since its
development, PCIT has been applied to a wide array of childhood problems and has
a significant evidence base for families with histories of child physical abuse.
The current study extended the existing literature by testing the effectiveness
and feasibility of PCIT in an urban domestic violence shelter with community
based clinicians delivering the treatment. Seven clinicians implemented PCIT with
parent-child dyads which included 21 preschool (M = 4.57 years; SD = 1.50)
children. Families completed assessments at baseline, mid-treatment, and post
treatment. Nine families completed PCIT (43%). Completion of PCIT was associated
with improved child behavior, parenting practices, and mental health symptoms.
Considerations for treatment delivery and future directions are discussed.
PMID- 28503061
TI - Use of 4-Fr versus 6-Fr Nasobiliary Catheter for Biliary Drainage: A Prospective,
Multicenter, Randomized, Controlled Study.
AB - Background and Aim. Endoscopic nasobiliary drainage (NBD) effects according to
diameter remain unclear. We aimed to assess the drainage effects of the 4-Fr and
6-Fr NBD catheters. Methods. This prospective, multicenter, randomized,
controlled study was conducted at Hiroshima University Hospital and related
facilities within Hiroshima Prefecture. Endoscopic retrograde
cholangiopancreatography (ERCP) in 246 patients revealed acute cholangitis,
obstructive jaundice, and/or extrahepatic cholestasis; 4-Fr or 6-Fr NBD catheters
were randomly allocated and placed in these patients. The primary endpoint was
the efficacy of NBD based on the technical success rate and clinical success
(rates of change in blood test and amount of bile output). Secondary endpoints
included the spontaneous catheter displacement rate and nasal discomfort.
Results. The technical success rate and clinical success did not differ
significantly between groups. No spontaneous catheter displacement was noted in
either group. Nasal discomfort due to catheter placement was significantly lower
in the 4-Fr group versus the 6-Fr group (24 h after ERCP: 2.4 versus 3.5 cm, P =
0.005; 48 h after ERCP: 2.2 versus 3.1 cm, P = 0.01). Conclusion. The 4-Fr NBD
catheter was not inferior to 6-Fr NBD catheter in terms of clinical success; the
4-Fr NBD catheter was useful to reduce nasal discomfort.
PMID- 28503062
TI - Contraction Sensing with Smart Braid McKibben Muscles.
AB - The inherent compliance of soft fluidic actuators makes them attractive for use
in wearable devices and soft robotics. Their flexible nature permits them to be
used without traditional rotational or prismatic joints. Without these joints,
however, measuring the motion of the actuators is challenging. Actuator-level
sensors could improve the performance of continuum robots and robots with
compliant or multi-degree-of-freedom joints. We make the reinforcing braid of a
pneumatic artificial muscle (PAM or McKibben muscle) "smart" by weaving it from
conductive, insulated wires. These wires form a solenoid-like circuit with an
inductance that more than doubles over the PAM contraction. The reinforcing and
sensing fibers can be used to measure the contraction of a PAM actuator with a
simple, linear function of the measured inductance. Whereas other proposed self
sensing techniques rely on the addition of special elastomers or transducers, the
technique presented in this work can be implemented without modifications of this
kind. We present and experimentally validate two models for Smart Braid sensors
based on the long solenoid approximation and the Neumann formula, respectively.
We test a McKibben muscle made from a Smart Braid in quasistatic conditions with
various end-loads and in dynamic conditions. We also test the performance of the
Smart Braid sensor alongside steel.
PMID- 28503063
TI - Severe symptoms of short tear break-up time dry eye are associated with
accommodative microfluctuations.
AB - AIM: Validating the hypothesis that accommodative microfluctuations (AMFs) may be
associated with severe symptoms in short tear break-up time (BUT) dry eye (DE).
METHODS: This study included 12 subjects with short BUT DE (age: 49.6+/-18.3
years). Diagnoses were performed based on the presence of DE symptoms, BUT <=5 s,
Schirmer score >5 mm, and negative keratoconjunctival epithelial damage. Tear
evaluation, AMF, and functional visual acuity (VA) examinations were conducted
before and after DE treatment. The AMF parameters evaluated were: total high
frequency component (HFC), HFC with low accommodation for the task of staring
into the distance (HFC1), HFC with high accommodation for deskwork (HFC2). A
subjective questionnaire of DE symptoms was also performed. RESULTS: Mean BUT
increased from 1.9+/-2.0 to 6.4+/-2.5 s after treatment (P<0.05). The mean
logarithm of the minimum angle of resolution functional VA significantly improved
(from 0.19+/-0.19 to 0.12+/-0.17; P<0.05). Mean power spectrum values for total
HFC and HFC1 decreased (from 61.3+/-5.7 to 53.8+/-6.6 dB and from 62.9+/-10.5 to
52.4+/-6.2 dB, respectively; P<0.05), while the mean HFC2 power spectrum values
did not differ before and after treatment (P>0.05). Subjective DE symptoms were
reduced in nine patients. CONCLUSION: Along with the improvement of BUT after
treatment, DE symptoms diminished and HFC1 and functional VA improved, suggesting
that tear film instability is associated with deterioration of functional VA,
AMF, and DE symptoms.
PMID- 28503064
TI - Combined intrastromal injection of amphotericin B and topical fluconazole in the
treatment of resistant cases of keratomycosis: a retrospective study.
AB - PURPOSE: To evaluate the efficacy of combination therapy of a single intrastromal
injection of amphotericin B and topical fluconazole in resistant cases of fungal
keratitis, and also topical amphotericin B as monotherapy in terms of the
duration of the recovery period and toxic drug effects. METHODS: This
retrospective 2-year study reviewed 68 cases of unilateral fungal keratitis
diagnosed by clinical features and positive laboratory culture results. Forty-one
cases were resistant and did not respond to monotherapy with an antifungal agent.
Thus, they were treated with a single intrastromal injection of amphotericin B in
addition to topical fluconazole as combined antifungal therapy, representing
group A. Twenty-seven cases were treated with topical amphotericin B as
antifungal monotherapy, representing group B. Topical atropine 1% and different
antibiotic eye drops were added to the antifungal agents in both groups. Follow
up of patient records was performed monitoring cure rate, duration of recovery
period, and toxic drug effects such as pain, burning sensation, and corneal
melting. RESULTS: The results revealed that group A, treated with combination
therapy, showed recovery of 34 cases (82.9%) with a mean duration of 24+/-6.42
days, significantly different from group B which showed recovery of 16 cases
(59.3%) with a mean duration of 39.66+/-13.6 days. Group A also showed less
manifestation of drug toxicity than group B. CONCLUSION: Combined intrastromal
injection of amphotericin B and topical fluconazole can provide a good modality
in the treatment of resistant cases of fungal keratitis, exhibiting highly potent
antifungal effects, shorter recovery period, and reduced corneal toxicity.
PMID- 28503065
TI - Serum cytokine levels related to exposure to volatile organic compounds and PM2.5
in dwellings and workplaces in French farmers - a mechanism to explain nonsmoking
COPD.
AB - Although French farmers smoke less on average than individuals from the general
population, they suffer more from COPD. Exposure to biological and chemical air
pollutants in the farm may be the cause of these higher COPD rates. This study
investigates the role of bio-contaminants, including the relationship of exposure
to volatile organic compounds (VOCs) and fine particulate matter (of diameter of
2.5 um [PM2.5]) objectively measured in the farm settings (dwellings and
workplaces) to serum cytokines involved in COPD, in a sample of 72 farmers from
50 farms in the Auvergne region, France. Mean concentrations of VOCs were highest
inside the home, while levels of PM2.5 were highest in workplaces (stables and
granaries). After adjusting for confounders, high exposure to PM2.5 was
significantly associated with a decreased level of serum cytokines (among others,
IL13: beta: -0.94, CI: -1.5 to -0.2, P-value =0.004; IL8: beta: -0.82, CI: -1.4
to -0.2, P-value =0.005) and high exposure to VOCs according to a VOC global
score with a decreased IL13 level (beta: -0.5, CI: -0.9 to -0.1, P-value =0.01).
Moreover, respiratory symptoms and diseases, including COPD, were associated with
a decreased level of serum cytokines significantly in the case of IL5. An
alteration of immune response balance in terms of cytokine levels in relation to
indoor chemical air pollution exposure may contribute to respiratory health
impairment in farmers.
PMID- 28503067
TI - Interdisciplinary collaboration in reablement - a qualitative study.
AB - BACKGROUND: In-depth knowledge regarding interdisciplinary collaboration, a key
feature in reablement, is scarce. OBJECTIVE: To elucidate how the
interdisciplinary collaboration in reablement worked in a Norwegian context.
SAMPLE AND METHODS: Seven focus group interviews were conducted with 33 health
care providers working in interdisciplinary reablement teams in seven
municipalities across the country. The focus group interviews were transcribed
and an hermeneutical analysis was conducted. RESULTS: The analysis resulted in
four main themes: "participant's own goals as a common interdisciplinary
platform", "a positive professional community", "learning from each other's
skills and competencies" and "new roles and joint efforts but specific
competencies". The results show that interdisciplinary collaboration in
reablement depends on participants defining their own rehabilitation goals, which
function as a professional unifying platform for the interdisciplinary
collaboration. The challenges for participants in reablement are often complex
and include assessments, effort and a need for close collaboration between
several different professionals. A tight interdisciplinary collaboration causes
major changes in roles, often from a particular role to a more general role with
broader job tasks. Although different professionals perform the same
rehabilitation tasks, it is important that each professional contributes their
unique competence and thus together they complete each other's competencies.
CONCLUSION: Factors that have a positive impact on interdisciplinary
collaboration in reablement are participants' definitions of their goals, number
and variety of professionals involved, how closely these professionals
collaborate, the amount of time for communication and shared planning and
decision making.
PMID- 28503066
TI - Essential oil-mediated glycerosomes increase transdermal paeoniflorin delivery:
optimization, characterization, and evaluation in vitro and in vivo.
AB - In this study, a novel glycerosome carrier containing essential oils was prepared
for topical administration of paeoniflorin (PF) to enhance its transdermal drug
delivery and improve drug absorption in the synovium. The formulation of
glycerosomes was optimized by a uniform design, and the final vehicle was
composed of 5% (w/v) phospholipid, 0.6% (w/v) cholesterol, and 10% (v/v)
glycerol, with 2% (v/v) Speranskia tuberculata essential oil (STO) as the
transdermal enhancer. The in vitro transdermal flux of PF loaded in the STO
glycerosomes was 1.4-fold, 1.6-fold, and 1.7-fold higher than those of
glycerosomes, liposomes, and tinctures, respectively. In vivo studies showed that
the use of STO-glycerosomes was associated with a 3.1-fold greater accumulation
of PF in the synovium than that of common glycerosomes. This finding was
confirmed by in vivo imaging studies, which found that the fluorescence intensity
of Cy5.5-loaded STO-glycerosomes in mice knee joints was 1.8-fold higher than
that of the common glycerosomes 5 h after administration. The glycerosomes
mediated by STO exhibited considerable skin permeability as well as improved drug
absorption in the synovium, indicating that STO-glycerosomes may be a potential
PF transdermal delivery vehicle for the treatment of rheumatoid arthritis caused
by synovium lesions.
PMID- 28503068
TI - A retrospective study on the prognostic value of preoperative
neutrophil/lymphocyte ratio in patients with primary small-cell carcinoma of the
esophagus.
AB - INTRODUCTION: There is increasing evidence that systemic inflammation influences
the prognosis in patients with malignant tumors. The aim of this research was to
investigate the prognostic value of neutrophil/lymphocyte ratio (NLR) in patients
with primary small-cell carcinoma of the esophagus. METHODS: This study
retrospectively analyzed 129 patients with primary small-cell carcinoma of the
esophagus who underwent esophagectomy in The Fourth Hospital of Hebei Medical
University between January 2008 and December 2010. NLRs were calculated by using
the following formula: peripheral neutrophil count/lymphocyte count (109/L).
Correlations of NLR with other clinicopathologic data and prognosis were
analyzed. The survival rate was calculated by Kaplan-Meier analysis. The
differences between groups were compared by using the log-rank test. Cox
regression was used to analyze the factors that may affect the survival of the
patients. RESULTS: The survival rate was found to be related to tumor stage,
tumor location, nodal metastasis, TNM stage, histology, adjuvant therapy, and NLR
(all P<0.05). High-NLR group had significantly poorer survival than low-NLR group
(1-, 3-, and 5-year survival rates: 46.6% vs 57.1%, 21.9% vs 50.0%, and 5.5% vs
23.2%, respectively, P=0.002). NLR was identified as an independent prognostic
factor for patients with primary small-cell carcinoma of the esophagus.
CONCLUSION: NLR is a valuable clinical marker in preoperative estimation as well
as prognosis prediction for patients with primary small-cell carcinoma of the
esophagus.
PMID- 28503069
TI - Downregulation of long noncoding RNA TUG1 inhibits proliferation and induces
apoptosis through the TUG1/miR-142/ZEB2 axis in bladder cancer cells.
AB - BACKGROUND: Bladder cancer is a common serious disease around the world. Long
noncoding RNAs (lncRNAs) have been demonstrated to participate in the development
and progression of various cancers, including bladder cancer. The aim of this
study was to investigate the effects of lncRNA taurine upregulated gene 1 (TUG1)
on proliferation and apoptosis in bladder cancer cell lines and the underlying
mechanism. METHODS: The levels of TUG1 were detected by quantitative real time
polymerase chain reaction (qRT-PCR) in bladder cancer tissues and cells. The mRNA
and protein levels of zinc finger E-box binding homeobox 2 (ZEB2) were measured
by qRT-PCR and Western blot analysis, respectively. The functional targets of
TUG1 were predicted by online softwares and confirmed by luciferase reporter
assay. The effects of TUG1 on cell proliferation and apoptosis were examined by
MTT and apoptosis assay, respectively. The expression levels of beta-catenin,
cyclinD1, and c-Myc in T24 cells were determined by Western blot analysis.
RESULTS: The levels of TUG1 and ZEB2 were significantly increased in bladder
cancer tissues and cells. Knockdown of either TUG1 or ZEB2 inhibited
proliferation and induced apoptosis in bladder cancer cells. Interestingly, ZEB2
overexpression reversed the effects of TUG1 knockdown on cell proliferation and
apoptosis. Moreover, ZEB2 was verified as a direct target of miR-142 and miR-142
could specially bind to TUG1. In addition, downregulation of TUG1 inhibited the
Wnt/beta-catenin pathway by regulating ZEB2 expression in bladder cancer cells.
CONCLUSION: Downregulation of TUG1 expression inhibited proliferation and induced
apoptosis in bladder cancer cells by targeting ZEB2 mediated by miR-142 through
the inactivation of Wnt/beta-catenin pathway.
PMID- 28503070
TI - Tyrosine kinase inhibitor combination therapy in first-line treatment of non
small-cell lung cancer: systematic review and network meta-analysis.
AB - INTRODUCTION: The introduction of epidermal growth factor receptor tyrosine
kinase inhibitors (EGFR-TKIs) has improved the outlook for patients with advanced
non-small-cell lung cancer (NSCLC) with EGFR+ mutations. However, most patients
develop resistance, with the result that median progression-free survival (PFS)
is12 months. Combining EGFR-TKIs with other agents, such as bevacizumab, is a
promising approach to prolonging remission. This systematic review and network
meta-analysis (NMA) were undertaken to assess available evidence regarding the
benefits of first-line combination therapy involving EGFR-TKIs in patients with
advanced NSCLC. METHODS: Literature searches were performed using relevant search
terms. Study-level pseudo-individual patient-level data (IPD) were recreated from
digitized Kaplan-Meier curve data, using a published algorithm. Study IPD were
analyzed using both the proportional hazards and the acceleration failure time
(AFT) survival models, and it was concluded that the AFT model was most
appropriate. An NMA was performed based on acceleration factors (AFs) using a
Bayesian framework to compare EGFR-TKIs and chemotherapy. RESULTS: Nine
randomized controlled trials were identified that provided data for EGFR-TKI
therapy in patients with EGFR+ tumors. These included studies of afatinib (n=3),
erlotinib (n=3), erlotinib plus bevacizumab (n=1) and gefitinib (n=2). Erlotinib
plus bevacizumab produced the greatest increase in PFS compared with
chemotherapy, with 1/AF being 0.24 (95% credible interval [CrI] 0.17, 0.34). This
combination also produced greater increases in PFS compared with EGFR-TKI
monotherapy: 1/AF versus afatinib, 0.51 (95% CrI 0.35, 0.73); versus erlotinib,
0.53 (95% CrI 0.39, 0.72) and versus gefitinib, 0.46 (95% CrI 0.32, 0.66). All
three EGFR-TKI monotherapies prolonged PFS compared with chemotherapy; estimates
of treatment effect ranged from 1/AF 0.53 (95% CrI 0.48, 0.60) for gefitinib to
1/AF 0.46 (95% CrI 0.40, 0.53) for erlotinib. There was no evidence for
differences between EGFR-TKI monotherapies, as all 95% CrIs included the null
value. CONCLUSION: Although data for erlotinib plus bevacizumab came from a
single Phase 2 study, the results of the NMA suggest that adding bevacizumab to
erlotinib may be a promising approach to improving the outcomes achieved with
EGFR-TKI monotherapy in patients with advanced EGFR+ NSCLC.
PMID- 28503073
TI - Response to the publication by Ueberall and Mueller-Schwefe.
PMID- 28503071
TI - The ecological community of commensal, symbiotic, and pathogenic gastrointestinal
microorganisms - an appraisal.
AB - The human gastrointestinal tract is inhabited by a vast population of bacteria,
numbering ~100 trillion. These microorganisms have been shown to play a
significant role in digestion, metabolism, and the immune system. The aim of this
study was to review and discuss how the human body interacts with its gut
microbiome and in turn the effects that the microorganisms have on its host,
overall resulting in a true mutualistic relationship.
PMID- 28503072
TI - Long-term clinical benefit and cost-effectiveness of an 8-week multimodal knee
osteoarthritis management program incorporating intra-articular sodium
hyaluronate (Hyalgan(r)) injections.
AB - BACKGROUND: Given the poor long-term effectiveness of focused nonsurgical knee
osteoarthritis (OA) treatments, alternative therapies are needed for patients who
have unsuccessfully exhausted nonsurgical options. METHODS: A telephone interview
was conducted in patients who participated in a single 8-week multimodal knee OA
treatment program (mean follow-up: 3.7 years, range: 2.7-4.9 years). The program
consisted of five intra-articular knee injections of sodium hyaluronate
(Hyalgan(r)), with each injection given 1 week apart, structured physical
therapy, knee bracing, and patient education. Clinical outcomes included knee
pain severity, Western Ontario and McMaster Universities Osteoarthritis Index
(WOMAC) subscores, current medication use, and history of total knee
arthroplasty. Base-case, subgroup, and sensitivity analyses were conducted to
determine the incremental cost-effectiveness ratio (ICER) of the treatment
program with comparisons made to historical literature controls undergoing usual
care. RESULTS: A total of 218 patients (54%) provided long-term follow-up data.
Knee pain severity decreased 60% and WOMAC subscores decreased 33%-42% compared
to baseline (all p<0.001). Total knee arthroplasty was performed in 22.8%
(81/356) of knees during followup. The treatment program was highly cost
effective compared to usual care with a base-case ICER of $6,000 per quality
adjusted life year (QALY). Results of subgroup analyses, one-way deterministic
sensitivity analyses, and second-order probabilistic sensitivity analyses
resulted in ICERs ranging from $3,996 to $10,493 per QALY. The percentage of
simulations with an ICER below willingness-to-pay limits was 97.2%, 98.9%, and
99.4% for the $50,000, $100,000, and $150,000 per QALY thresholds, respectively.
CONCLUSION: Participation in a single 8-week knee OA treatment program, which
included one cycle of five intra-articular knee injections of sodium hyaluronate
given at weekly intervals, is highly cost-effective and provides clinically
meaningful reductions in patient symptoms that are maintained over 3.7 years mean
follow-up.
PMID- 28503074
TI - Acute radiation dermatitis in breast cancer patients: challenges and solutions.
AB - Nearly all women who receive radiotherapy (RT) for breast cancer experience some
degree of radiation dermatitis. However, evidence describing the appropriate
management of radiation dermatitis is often lacking or contradictory. Here, we
summarize the available literature regarding radiation dermatitis causes, the
presentation and timing of symptoms, methods for dermatitis assessment and
prevention, and review evidence-based management strategies.
PMID- 28503076
TI - Positive predictive value of peptic ulcer diagnosis codes in the Danish National
Patient Registry.
AB - BACKGROUND: Diagnoses of peptic ulcer are registered in the Danish National
Patient Registry (DNPR) for administrative as well as research purposes, but it
is unknown whether the coding validity depends on the location of the ulcer.
OBJECTIVE: To validate the International Classification of Diseases, 10th
revision diagnosis codes of peptic ulcer in the DNPR by estimating positive
predictive values (PPVs) for gastric and duodenal ulcer diagnoses. METHODS: We
identified all patients registered with a hospital discharge diagnosis of peptic
ulcer from Aarhus University Hospital, Denmark, in 1995-2006. Among them, we
randomly selected 200 who had an outpatient gastroscopy at the time of ulcer
diagnosis. We reviewed the findings from these gastroscopies to confirm the
presence of peptic ulcer and its location. We calculated PPVs and corresponding
95% confidence intervals (CIs) of gastric and duodenal ulcer diagnoses, using
descriptions from the gastroscopic examinations as standard reference. RESULTS:
In total, 182 records (91%) were available for review. The overall PPV of peptic
ulcer diagnoses in DNPR was 95.6% (95% CI 91.5-98.1), with PPVs of 90.3% (95% CI
82.4-95.5) for gastric ulcer diagnoses, and 94.4% (95% CI 87.4-98.2) for duodenal
ulcer diagnoses. PPVs were constant over time. CONCLUSION: The PPV of
uncomplicated peptic ulcer diagnoses in the DNPR is high, and the location of the
ulcers is registered correctly in most cases, indicating that the diagnoses are
useful for research purposes.
PMID- 28503075
TI - Imprint cytology versus frozen section analysis for intraoperative assessment of
sentinel lymph node in breast cancer.
AB - INTRODUCTION: Sentinel lymph node (SLN) biopsy is the gold standard for surgical
staging of the axilla in breast cancer (BC). Frozen section (FS) remains the most
popular means of intraoperative SLN diagnosis. Imprint cytology (IC) has also
been suggested as a less expensive and equally accurate alternative to FS. The
aim of our study was to perform a direct comparison between IC and FS on the same
SLNs of BC cases operated in a single center by the same surgical team. MATERIALS
AND METHODS: Into this prospective study we enrolled 60 consecutive patients with
histologically proven T1-T3 BC and clinically negative axilla. Sentinel nodes
were detected using a standard protocol. The SLN(s) was always assessed by IC as
well as FS analysis and immunohistochemistry. Nevertheless, all intraoperative
decisions were based on FS analysis. RESULTS: During the study period 60 patients
with invasive BC were registered, with 80 SLNs harvested. Mean number of SLN(s)
identified for each patient was 1.33. The sensitivity and specificity were 90%
and 100%, respectively, for IC, and 80% and 100% for FS. Relevant
positive/negative predictive values were 100%/98% for IC and 100%/96.15%,
respectively, for FS. Overall accuracy was 98% for IC and 97% for FS. Therefore,
statistically significant difference between the two methods in the detection of
positive nodes was not elucidated (p=1.000). CONCLUSIONS: IC appeared to be
marginally more sensitive than FS in detecting SLN metastatic activity. Overall
accuracy was 98.75%. With regard to the primary lesion characteristics, we
conclude that initial lesion size and lymphovascular invasion play a pivotal role
in metastatic involvement of the SLN with the dimensions of metastasis bearing no
correlation with tumor size. Therefore, IC appears to be a sensitive and accurate
method for the intraoperative assessment of SLN in BC patients, but further
studies are required to confirm this interesting data.
PMID- 28503077
TI - An unusual association of headache, epilepsy, and late-onset Kleist's
pseudodepression syndrome in frontal lobe cavernoma of the cerebral left
hemisphere.
AB - Cerebral cavernous angioma or cavernoma is a benign vascular malformation,
usually asymptomatic. It is infrequent and often its discovery is incidental, a
so-called incidentaloma. However, these lesions can be symptomatic, causing
headaches, epilepsy, cerebral hemorrhage and other neurological signs depending
on the brain area involved. Frontal localization is responsible for psychiatric
disorders, particularly the prefrontal region, leading to prefrontal syndrome, a
condition common in all frontal lobe tumors. Psychopathological syndrome can be
depression-type, pseudodepression syndrome or maniac-type, pseudomaniac syndrome.
Surgical treatment of lesions like this may not always be possible due to their
location in eloquent areas. In this study, we describe an unusual association of
migraine-like headache, epilepsy and frontal lobe pseudodepression late-onset
syndrome in the same patient. We have considered this case interesting mainly for
the rarity of both a headache with migraine features and for the late onset of
pseudodepression syndrome. Pathophysiology underlying migraine-like headache and
that concerning the late-onset pseudodepression frontal lobe syndrome seems to be
unclear. This case leads to further hypotheses about the mechanisms responsible
for headache syndromes and psychopathological disorders, in the specific case
when caused by a cerebral frontal lobe lesion.
PMID- 28503079
TI - Using mobile audience response systems to enhance medical education: a medical
student perspective.
PMID- 28503080
TI - A Bayesian mixture model for missing data in marine mammal growth analysis.
AB - Much of what is known about bottle nose dolphin (Tursiops truncatus) anatomy and
physiology is based on necropsies from stranding events. Measurements of total
body length, total body mass, and age are used to estimate growth. It is more
feasible to retrieve and transport smaller animals for total body mass
measurement than larger animals, introducing a systematic bias in sampling.
Adverse weather events, volunteer availability, and other unforeseen
circumstances also contribute to incomplete measurement. We have developed a
Bayesian mixture model to describe growth in detected stranded animals using data
from both those that are fully measured and those not fully measured. Our
approach uses a shared random effect to link the missingness mechanism (i.e.
full/partial measurement) to distinct growth curves in the fully and partially
measured populations, thereby enabling drawing of strength for estimation. We use
simulation to compare our model to complete case analysis and two common multiple
imputation methods according to model mean square error. Results indicate that
our mixture model provides better fit both when the two populations are present
and when they are not. The feasibility and utility of our new method is
demonstrated by application to South Carolina strandings data.
PMID- 28503078
TI - Variations in the clinical practice of physicians managing Takayasu arteritis: a
nationwide survey.
AB - OBJECTIVE: Takayasu arteritis (TAK) is a large vessel vasculitis that
predominately affects young women and can cause severe ischemic complications.
Given the rarity of TAK, the management of this condition is challenging. We aim
to describe current rheumatologist practices for the management of TAK and
identify discrepancies and gaps in knowledge. METHODS: An online survey
(developed by the Canadian Vasculitis Network and approved by the Canadian
Rheumatology Association) containing 48 questions with regard to the diagnosis,
monitoring and treatment of TAK was distributed to 495 Canadian adult and
pediatric rheu-matologists by email. RESULTS: Sixty-six rheumatologists completed
the survey (13% response rate): the majority (73%) were from academic centers and
<=25% reported managing more than ten patients in their career. For establishing
the diagnosis of TAK, they relied on a combination of signs and symptoms of
ischemia, elevations of inflammatory markers and vascular imaging (typically
computed tomography and magnetic resonance angiography). The frequency of
monitoring for disease activity and the methods employed (clinical, laboratory or
imaging) were variable. All physicians used corticosteroids for the treatment of
TAK, but 42% would treat for at least 6-12 months, 26% for 12-24 months and 23%
would never stop corticosteroids. Fifty-three percent would always use an
immunosuppressant (most commonly methotrexate or azathioprine) in addition to
corticosteroids and the remainder would only start an immunosuppressant in
patients with refractory or relapsing disease. CONCLUSION: Physician practices
for the management of TAK are variable, suggesting that there are knowledge gaps,
which may impact outcomes in patients with TAK.
PMID- 28503081
TI - Feeding intolerance, inflammation, and neurobehaviors in preterm infants.
AB - PURPOSE: Identifying relationships between feeding intolerance (FI),
inflammation, and early measures of neurodevelopment may provide the basis for
clinically relevant assessments for NICU clinicians and staff. The purpose of
this secondary analysis was to examine the relationship of FI to inflammatory
markers and/or neurobehaviors in the first week of life. METHODS: This was a
retrospective, matched case-control design with data drawn from 114 infants born
at <=32 weeks gestation. RESULTS: Eight infants developed FI prior to full
enteral feedings. These infants were more likely to have dysregulated levels of
cytokines, specifically IL6, and lower neurodevelopmental scores compared to
infants without FI. CONCLUSIONS: Results suggest physiologic dysregulation and an
immature nervous system may contribute to the phenomenon of FI in preterm
infants. Further research to identify the role of the brain-gut-immune axis on FI
and other GI complications in this population is warranted.
PMID- 28503082
TI - Postcolonial penality: Liberty and repression in the shadow of independence,
India c. 1947.
AB - This article reports primary archival data on the colonial penal history of
British India and its reconfiguration into the postcolonial Indian state. It
introduces criminologists to frameworks through which postcolonial scholars have
sought to make sense of the continuities and discontinuities of rule across the
colonial/postcolonial divide. The article examines the postcolonial life of one
example of colonial penal power, known as the criminal tribes policy, under which
more than three million Indian subjects of British rule were restricted in their
movements, subject to a host of administrative rules and sometimes severe
punishments, sequestered in settlements and limited in access to legal redress.
It illustrates how at the birth of the postcolonial Indian state, encompassing
visions of a liberal, unfettered and free life guaranteed in a new Constitution
and charter of Fundamental Rights, freedom for some was to prove as elusive as
citizens as it had been as subjects.
PMID- 28503083
TI - Vegetation resurvey is robust to plot location uncertainty.
AB - AIM: Resurveys of historical vegetation plots are increasingly used for the
assessment of decadal changes in plant species diversity and composition.
However, historical plots are usually relocated only approximately. This
potentially inflates temporal changes and undermines results. LOCATION: Temperate
deciduous forests in Central Europe. METHODS: To explore if robust conclusions
can be drawn from resurvey studies despite location uncertainty, we compared
temporal changes in species richness, frequency, composition and compositional
heterogeneity between exactly and approximately relocated plots. We hypothesized
that compositional changes should be lower and changes in species richness should
be less variable on exactly relocated plots, because pseudo-turnover inflates
temporal changes on approximately relocated plots. RESULTS: Temporal changes in
species richness were not more variable and temporal changes in species
composition and compositional heterogeneity were not higher on approximately
relocated plots. Moreover, the frequency of individual species changed similarly
on both plot types. MAIN CONCLUSIONS: The resurvey of historical vegetation plots
is robust to uncertainty in original plot location and, when done properly,
provides reliable evidence of decadal changes in plant communities. This provides
important background for other resurvey studies and opens up the possibility for
large-scale assessments of plant community change.
PMID- 28503084
TI - Carbon Dioxide Utilization by the Five-Membered Ring Products of Cyclometalation
Reactions.
AB - In carbon dioxide utilization by cyclometalated five-membered ring products, the
following compounds are used in four types of applications: 1. 2-Phenylpyrazole
iridium compounds, pincer phosphine iridium compounds and 2-phenylimidazoline
iridium compounds are used as catalysts for both formic acid production from CO2
and H2, and hydrogen production from the formic acid. This formic acid can be a
useful agent for H2 production and storage for fuel cell electric vehicles. 2.
Other chemicals, e.g., dimethyl carbonate, methane, methanol and CO, are produced
with dimethylaminomethylphenyltin compounds, pincer phosphine iridium compounds,
pincer phosphine nickel compound and ruthenium carbene compound or 2
phenylpyridine iridium compounds, and phenylbenzothiazole iridium compounds as
the catalysts for the reactions with CO2. 3. The five-membered ring intermediates
of cyclometalation reactions with the conventional substrates react with carbon
dioxide to afford their many types of carboxylic acid derivatives. 4. Carbon
dioxide is easily immobilized at room temperature with immobilizing agents such
as pincer phosphine nickel compounds, pincer phosphine palladium compounds,
pincer N,N-dimethylaminomethyltin compounds and tris(2-pyridylthio)methane zinc
compounds.
PMID- 28503086
TI - Anticancer Natural Compounds: Molecular Mechanisms and Functions. Part I.
PMID- 28503085
TI - Physicochemical properties and in vitro cytotoxicity of iron oxide-based
nanoparticles modified with antiangiogenic and antitumor peptide A7R.
AB - Superparamagnetic iron oxide-based nanoparticles (SPIONs) are promising carriers
as targeted drug delivery vehicles, because they can be guided to their target
with the help of an external magnetic field. Functionalization of nanoparticles'
surface with molecules, which bind with high affinity to receptors on target
tissue significantly facilitates delivery of coated nanoparticles to their
targeted site. Here, we demonstrate conjugation of an antiangiogenic and
antitumor peptide ATWLPPR (A7R) to SPIONs modified with sebacic acid (SPIONs-SA).
Successful conjugation was confirmed by various analytical techniques (FTIR,
SERS, SEM-EDS, TEM, TGA). Cell cytotoxicity studies, against two cell lines
(HUVEC and MDA-MB-231) indicated that SPIONs modified with A7R reduced HUVEC cell
viability at concentrations higher than 0.01 mg Fe/mL, in comparison to cells
that were exposed to either the nanoparticles modified with sebacic acid or A7R
peptide solely, what might be partially caused by a process of internalization.
PMID- 28503088
TI - Restoring TRAIL Induced Apoptosis Using Naturopathy. Hercules Joins Hand with
Nature to Triumph Over Lernaean Hydra.
AB - Cancer is a multifaceted disease. Our deepened knowledge about genetic and
biological mechanisms of cancer cells presents an opportunity to explore the
inter-individual differences in the body's ability to metabolize and respond to
different nutrients. It is becoming progressively more understandable that the
deregulation of several signaling pathways and the alterations in apoptotic
response are some of the major determinants that underpin carcinogenesis. Tumor
necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL)-mediated signaling has
gained a remarkable appreciation because of its ability to selectively induce
apoptosis in cancer cells leaving normal cells intact. However, technological
advances have started to shed light on underlying mechanisms of resistance
against TRAIL-induced apoptosis in cancer cells. The impairment of TRAIL-mediated
apoptosis includes various factors ranging from the loss or down regulation of
TRAIL receptors or pro-apoptotic proteins to the up regulation of anti-apoptotic
proteins. Intriguingly to mention that there is an ever-increasing number of
natural herbal extracts (phytometabolites), which have been explored to date for
their potential action in restoring apoptosis TRAIL-mediated in cancer cells. In
this review, we will highlight the progress in understanding the mechanisms opted
by phenolic compounds in overcoming TRAIL resistance.
PMID- 28503089
TI - Anticancer Chemodiversity of Ranunculaceae Medicinal Plants: Molecular Mechanisms
and Functions.
AB - The buttercup family, Ranunculaceae, comprising more than 2,200 species in at
least 62 genera, mostly herbs, has long been used in folk medicine and worldwide
ethnomedicine since the beginning of human civilization. Various medicinal
phytometabolites have been found in Ranunculaceae plants, many of which, such as
alkaloids, terpenoids, saponins, and polysaccharides, have shown anti-cancer
activities in vitro and in vivo. Most concerns have been raised for two epiphany
molecules, the monoterpene thymoquinone and the isoquinoline alkaloid berberine.
At least 17 genera have been enriched with anti-cancer phytometabolites. Some
Ranunculaceae phytometabolites induce the cell cycle arrest and apoptosis of
cancer cells or enhance immune activities, while others inhibit the
proliferation, invasion, angiogenesis, and metastasis, or reverse the multi-drug
resistance of cancer cells thereby regulating all known hallmarks of cancer.
These phytometabolites could exert their anti-cancer activities via multiple
signaling pathways. In addition, absorption, distribution, metabolism, and
excretion/toxicity properties and structure/activity relationships of some
phytometabolites have been revealed assisting in the early drug discovery and
development pipelines. However, a comprehensive review of the molecular
mechanisms and functions of Ranunculaceae anti-cancer phytometabolites is
lacking. Here, we summarize the recent progress of the anti-cancer chemo- and
pharmacological diversity of Ranunculaceae medicinal plants, focusing on the
emerging molecular machineries and functions of anti-cancer phytometabolites.
Gene expression profiling and relevant omics platforms (e.g. genomics,
transcriptomics, proteomics, and metabolomics) could reveal differential effects
of phytometabolites on the phenotypically heterogeneous cancer cells.
PMID- 28503090
TI - Compounds From Celastraceae Targeting Cancer Pathways and Their Potential
Application in Head and Neck Squamous Cell Carcinoma: A Review.
AB - Squamous cell carcinoma of the head and neck is one of the most common cancer
types worldwide. It initiates on the epithelial lining of the upper aerodigestive
tract, at most instances as a consequence of tobacco and alcohol consumption.
Treatment options based on conventional therapies or targeted therapies under
development have limited efficacy due to multiple genetic alterations typically
found in this cancer type. Natural products derived from plants often possess
biological activities that may be valuable in the development of new therapeutic
agents for cancer treatment. Several genera from the family Celastraceae have
been studied in this context. This review reports studies on chemical
constituents isolated from species from the Celastraceae family targeting cancer
mechanisms studied to date. These results are then correlated with molecular
characteristics of head and neck squamous cell carcinoma in an attempt to
identify constituents with potential application in the treatment of this complex
disease at the molecular level.
PMID- 28503087
TI - Established Human Cell Lines as Models to Study Anti-leukemic Effects of
Flavonoids.
AB - Despite the extensive work on pathological mechanisms and some recent advances in
the treatment of different hematological malignancies, leukemia continues to
present a significant challenge being frequently considered as incurable disease.
Therefore, the development of novel therapeutic agents with high efficacy and low
toxicity is urgently needed to improve the overall survival rate of patients. In
this comprehensive review article, the current knowledge about the anticancer
activities of flavonoids as plant secondary polyphenolic metabolites in the most
commonly used human established leukemia cell lines (HL-60, NB4, KG1a, U937, THP
1, K562, Jurkat, CCRF- CEM, MOLT-3, and MOLT-4) is compiled, revealing clear anti
proliferative, pro-apoptotic, cell cycle arresting, and differentiation inducing
effects for certain compounds. Considering the low toxicity of these substances
in normal blood cells, the presented data show a great potential of flavonoids to
be developed into novel anti-leukemia agents applicable also in the malignant
cells resistant to the current conventional chemotherapeutic drugs.
PMID- 28503092
TI - Management of Gene Variants of Unknown Significance: Analysis Method and Risk
Assessment of the VHL Mutation p.P81S (c.241C>T).
AB - BACKGROUND: Evaluation of the pathogenicity of a gene variant of unknown
significance (VUS) is crucial for molecular diagnosis and genetic counseling, but
can be challenging. This is especially so in phenotypically variable diseases,
such as von Hippel-Lindau disease (vHL). vHL is caused by germline mutations in
the VHL gene, which predispose to the development of multiple tumors such as
central nervous system hemangioblastomas and renal cell carcinoma (RCC).
OBJECTIVE: We propose a method for the evaluation of VUS pathogenicity through
our experience with the VHL missense mutation c.241C>T (p.P81S). METHOD: 1)
Clinical evaluation of known variant carriers: We evaluated a family of five VHL
p.P81S carriers, as well as the clinical characteristics of all the p.P81S
carriers reported in the literature; 2) Evaluation of tumor tissue via genetic
analysis, histology, and immunohistochemistry (IHC); 3) Assessment of the
variant's impact on protein structure and function, using multiple databases, in
silico algorithms, and reports of functional studies. RESULTS: Only one family
member had clinical signs of vHL with early-onset RCC. IHC analysis showed no VHL
protein expressed in the tumor, consistent with biallelic VHL inactivation. The
majority of in silico algorithms reported p.P81S as possibly pathogenic in
relation to vHL or RCC, but there were discrepancies. Functional studies suggest
that p.P81S impairs the VHL protein's function. CONCLUSION: The VHL p.P81S
mutation is most likely a low-penetrant pathogenic variant predisposing to RCC
development. We suggest the above-mentioned method for VUS evaluation with use of
different methods, especially a variety of in silico methods and tumor tissue
analysis.
PMID- 28503093
TI - Alarms about structural alerts.
AB - Structural alerts are widely accepted in chemical toxicology and regulatory
decision support as a simple and transparent means to flag potential chemical
hazards or group compounds into categories for read-across. However, there has
been a growing concern that alerts disproportionally flag too many chemicals as
toxic, which questions their reliability as toxicity markers. Conversely, the
rigorously developed and properly validated statistical QSAR models can
accurately and reliably predict the toxicity of a chemical; however, their use in
regulatory toxicology has been hampered by the lack of transparency and
interpretability. We demonstrate that contrary to the common perception of QSAR
models as "black boxes" they can be used to identify statistically significant
chemical substructures (QSAR-based alerts) that influence toxicity. We show
through several case studies, however, that the mere presence of structural
alerts in a chemical, irrespective of the derivation method (expert-based or QSAR
based), should be perceived only as hypotheses of possible toxicological effect.
We propose a new approach that synergistically integrates structural alerts and
rigorously validated QSAR models for a more transparent and accurate safety
assessment of new chemicals.
PMID- 28503094
TI - The nature, characteristics and associations of care home staff stress and
wellbeing: a national survey.
AB - BACKGROUND: The majority of residents in care homes in the United Kingdom are
living with dementia or significant memory problems. Caring in this setting can
be difficult and stressful for care staff who work long hours, have little
opportunity for training, are poorly paid and yet subject to high expectation.
This may affect their mental and physical wellbeing, cause high rates of staff
turnover and absenteeism, and affect the quality of care they provide. The main
objective of this survey was to explore the nature, characteristics and
associations of stress in care home staff. METHODS: Staff working in a stratified
random sample of care homes within Wales completed measures covering: general
health and wellbeing (SF-12); stress (Work Stress Inventory); job content
(Karasek Job Content); approach to, and experience of, working with people living
with dementia (Approaches to Dementia Questionnaire; and Experience of Working
with Dementia Patients); and Productivity and Health Status (SPS-6). Multiple
linear regressions explored the effects of home and staff characteristics on
carers. RESULTS: 212 staff from 72 care homes completed questionnaires. Staff
from nursing homes experienced more work stress than those from residential homes
(difference 0.30; 95% confidence interval (CI) from 0.10 to 0.51; P < 0.01), and
were more likely to report that their health reduced their ability to work
(difference -4.77; CI -7.80 to -1.73; P < 0.01). Psychological demands on nurses
were higher than on other staff (difference = 1.57; CI 0.03 to 3.10; P < 0.05). A
positive approach to dementia was more evident in those trained in dementia care
(difference 8.54; CI 2.31 to 14.76; P < 0.01), and in staff working in local
authority homes than in the private sector (difference 7.75; CI 2.56 to 12.94; P
< 0.01). CONCLUSIONS: Our study highlights the importance of dementia training in
care homes, with a particular need in the private sector. An effective
intervention to reduce stress in health and social care staff is required,
especially in nursing and larger care homes, and for nursing staff. TRIAL
REGISTRATION: ISRCTN registry: ISRCTN80487202. Registered 24 July 2013.
PMID- 28503091
TI - Natural Compounds as Anticancer Agents Targeting DNA Topoisomerases.
AB - DNA topoisomerases are important cellular enzymes found in almost all types of
living cells (eukaryotic and prokaryotic). These enzymes are essential for
various DNA metabolic processes e.g. replication, transcription, recombination,
chromosomal decatenation etc. These enzymes are important molecular drug targets
and inhibitors of these enzymes are widely used as effective anticancer and
antibacterial drugs. However, topoisomerase inhibitors have some therapeutic
limitations and they exert serious side effects during cancer chemotherapy. Thus,
development of novel anticancer topoisomerase inhibitors is necessary for
improving cancer chemotherapy. Nature serves as a repertoire of structurally and
chemically diverse molecules and in the recent years many DNA topoisomerase
inhibitors have been identified from natural sources. The present review
discusses anticancer properties and therapeutic importance of eighteen recently
identified natural topoisomerase inhibitors (from the year 2009 to 2015).
Structural characteristics of these novel inhibitors provide backbones for
designing and developing new anticancer drugs.
PMID- 28503096
TI - Affect recognition among adolescents in therapeutic schools: relationships with
posttraumatic stress disorder and conduct disorder symptoms.
AB - BACKGROUND: Posttraumatic stress disorder (PTSD) and conduct disorder (CD)
symptoms often co-occur in adolescence, but little is known about whether they
show common or distinct emotional processing deficits. METHOD: We examined the
effects of PTSD and CD symptoms on facial affect processing in youth with
emotional and behavior problems. Teens enrolled in therapeutic day schools (N =
371; ages 13-19) completed a structured diagnostic assessment and the Diagnostic
Analysis of Nonverbal Accuracy-2 facial affect recognition task. RESULTS: PTSD
symptoms were associated with deficits in the recognition of angry facial
expressions, specifically the false identification of angry faces as fearful. CD
symptoms were associated with greater difficulty correctly identifying sadness.
CONCLUSIONS: Findings suggest specificity in the relationships of PTSD and CD
symptoms with emotional processing.
PMID- 28503097
TI - Asthma management among allergists in Italy: results from a survey.
AB - BACKGROUND: In Europe more than 50% of asthmatic treated patients have not well
controlled asthma. Asthma affects about 2.5 million of patients in Italy. AIMS
AND OBJECTIVES: The present survey aims at investigating how Italian allergists
approach asthmatic patients, in order to highlight pitfalls and unmet needs
concerning real-life asthma management. METHODS: An anonymous 16 item web
questionnaire was available (April-October 2015) to all allergists who visited
the web site of SIAAIC (Societa Italiana di Allergologia, Asma Immunologia
Clinica). Those who wished to give their contribution had the opportunity to
answer about epidemiology, risk factors, treatment approaches, and adherence to
therapy. RESULTS: One hundred and seventy four allergists answered the survey.
54% of them reported up to 10 patient visits per week and 35.3% between 10 and
30. The most frequent reasons of follow up visits are routine check-up (56.5% of
allergists), and worsening of symptoms (41% of allergists). Nocturnal apnoeas,
gastro-esophageal reflux and obesity are the most important comorbidities/risk
factors of poorly controlled asthma. Bronchial hyper-responsiveness, increased NO
levels and reduced exercise tolerance are the most important indicators of asthma
severity. Concerning therapy, ICS combined with LABA is the treatment of choice
suitable for the majority of patients. A rapid onset of action and a flexible ICS
dosage are indicated as the optimal characteristics for achieving the therapeutic
goals. Poor adherence to therapy is an important reason for symptom worsening for
the majority of allergists. Complex dosage regimens and economic aspects are
considered the most important factors impacting on adherence. CONCLUSIONS:
Allergists are involved in the management of asthma, regularly seeing their
patients. Co-morbidities are frequent in asthmatic patients and may impact
negatively on disease control, thus identifying patients who need a more careful
and strict monitoring. Airway hyper-responsiveness to methacholine challenge test
and nitric oxide are considered important indicators of asthma severity. The
combination of LABA and inhaled steroids is considered the treatment of choice
for most asthmatic patients, in keeping with broad evidence indicating that the
combination therapy is more effective and rapid in gaining asthma control than
inhaled corticosteroids alone. Adherence to medication regimens is considered of
essence to achieve the therapeutic goals.
PMID- 28503095
TI - The cholesterol metabolite 27-hydroxycholesterol stimulates cell proliferation
via ERbeta in prostate cancer cells.
AB - BACKGROUND: For every six men, one will be diagnosed with prostate cancer (PCa)
in their lifetime. Estrogen receptors (ERs) are known to play a role in prostate
carcinogenesis. However, it is unclear whether the estrogenic effects are
mediated by estrogen receptor alpha (ERalpha) or estrogen receptor beta (ERbeta).
Although it is speculated that ERalpha is associated with harmful effects on PCa,
the role of ERbeta in PCa is still ill-defined. The cholesterol oxidized
metabolite 27-hydroxycholesterol (27-OHC) has been found to bind to ERs and act
as a selective ER modulator (SERM). Increased 27-OHC levels are found in
individuals with hypercholesterolemia, a condition that is suggested to be a risk
factor for PCa. METHODS: In the present study, we determined the extent to which
27-OHC causes deleterious effects in the non-tumorigenic RWPE-1, the low
tumorigenic LNCaP, and the highly tumorigenic PC3 prostate cancer cells. We
conducted cell metabolic activity and proliferation assays using MTS and CyQUANT
dyes, protein expression analyses via immunoblots and gene expression analyses
via RT-PCR. Additionally, immunocytochemistry and invasion assays were performed
to analyze intracellular protein distribution and quantify transepithelial cell
motility. RESULTS: We found that incubation of LNCaP and PC3 cells with 27-OHC
significantly increased cell proliferation. We also demonstrate that the ER
inhibitor ICI 182,780 (fulvestrant) significantly reduced 27-OH-induced cell
proliferation, indicating the involvement of ERs in proliferation. Interestingly,
ERbeta levels, and to a lesser extent ERalpha, were significantly increased
following incubation of PCa cells with 27-OHC. Furthermore, in the presence of
the ERbeta specific inhibitor, PHTPP, 27-OHC-induced proliferation is attenuated.
CONCLUSIONS: Altogether, our results show for the first time that 27-OHC, through
ER activation, triggers deleterious effect in prostate cancer cell lines. We
propose that dysregulated levels of 27-OHC may trigger or exacerbate prostate
cancer via acting on ERbeta.
PMID- 28503098
TI - Absence of 4-1BB reduces obesity-induced atrophic response in skeletal muscle.
AB - Obesity-induced inflammation causes skeletal muscle atrophy accompanied by
disruption of oxidative metabolism and is implicated in metabolic complications
such as insulin resistance and type 2 diabetes. We previously reported that 4
1BB, a member of the tumor necrosis factor receptor superfamily, participated in
obesity-induced skeletal muscle inflammation. Here, we show that the absence of 4
1BB in obese mice fed a high-fat diet led to a decrease in expression of atrophic
factors (MuRF1 and Atrogin-1) with suppression of NF-kappaB activity, and that
this was accompanied by increases in mitochondrial oxidative metabolic
genes/proteins (e.g., PGC-1alpha, CPT1beta, etc.) expression and oxidative muscle
fibers marker genes/proteins in the skeletal muscle. These findings suggest that
4-1BB-mediated inflammatory signaling could be a potential target for combating
obesity-related muscle atrophy and metabolic derangement in skeletal muscle.
PMID- 28503100
TI - Age and gender considerations for technology-assisted delivery of therapy for
substance use disorder treatment: A patient survey of access to electronic
devices.
AB - BACKGROUND: Technology-assisted treatment (TAT) can be an effective supplement to
established face-to-face therapy modalities with a growing literature in
substance use disorder (SUD) treatment. TAT access, interest, and familiarity are
potential limitations to the use and efficacy of these approaches to treatment.
METHODS: 174 participants in outpatient SUD treatment were administered a survey
regarding technology device and Internet access, and interest in engaging in TAT
SUD counseling (SUDC). The group was dichotomized by mean age and gender to
examine potential variations in in these subgroups. RESULTS: Forty-three (43%) of
participants were female, and the mean age was 44.8 years, and 89% of
participants had Internet access. 83% of participants were interested in TAT for
SUD counseling; 81% expected it to be at least "moderately helpful." 34% of
participants noted they would choose to continue face-to-face therapy
exclusively. 91% of participants had cell phones, but only 50% could access data
or the Internet via their handheld device. 80% of participants stated they would
be interested in trying SUDC via their phone. Women had a higher preference for
computer-based SUDC than men, with gender being significantly correlated with TAT
perceive helpfulness. CONCLUSION: These findings suggest that patients in
outpatient SUD treatment have access to resources for TAT implementation,
although access was not always readily available. Future research will be needed
to determine whether the technology that this population possesses will be able
to support the evolving TAT modalities and whether interest in TAT across age and
gender groups equalizes over time.
PMID- 28503101
TI - L1-Regularized Least Squares for Support Recovery of High Dimensional Single
Index Models with Gaussian Designs.
AB - It is known that for a certain class of single index models (SIMs) [Formula: see
text], support recovery is impossible when X ~ ??(0, ?? p*p ) and a model
complexity adjusted sample size is below a critical threshold. Recently, optimal
algorithms based on Sliced Inverse Regression (SIR) were suggested. These
algorithms work provably under the assumption that the design X comes from an
i.i.d. Gaussian distribution. In the present paper we analyze algorithms based on
covariance screening and least squares with L1 penalization (i.e. LASSO) and
demonstrate that they can also enjoy optimal (up to a scalar) rescaled sample
size in terms of support recovery, albeit under slightly different assumptions on
f and epsilon compared to the SIR based algorithms. Furthermore, we show more
generally, that LASSO succeeds in recovering the signed support of beta0 if X ~
?? (0, Sigma), and the covariance Sigma satisfies the irrepresentable condition.
Our work extends existing results on the support recovery of LASSO for the linear
model, to a more general class of SIMs.
PMID- 28503099
TI - Water deficit mechanisms in perennial shrubs Cerasus humilis leaves revealed by
physiological and proteomic analyses.
AB - BACKGROUND: Drought (Water deficit, WD) poses a serious threat to extensively
economic losses of trees throughout the world. Chinese dwarf cherry (Cerasus
humilis) is a good perennial plant for studying the physiological and
sophisticated molecular network under WD. The aim of this study is to identify
the effect of WD on C. humilis through physiological and global proteomics
analysis and improve understanding of the WD resistance of plants. METHODS:
Currently, physiological parameters were applied to investigate C. humilis
response to WD. Moreover, we used two-dimensional gel electrophoresis (2DE) to
identify differentially expressed proteins in C. humilis leaves subjected to WD
(24 d). Furthermore, we also examined the correlation between protein and
transcript levels. RESULTS: Several physiological parameters, including relative
water content and Pn were reduced by WD. In addition, the malondialdehyde (MDA),
relative electrolyte leakage (REL), total soluble sugar, and proline were
increased in WD-treated C. humilis. Comparative proteomic analysis revealed 46
protein spots (representing 43 unique proteins) differentially expressed in C.
humilis leaves under WD. These proteins were mainly involved in photosynthesis,
ROS scavenging, carbohydrate metabolism, transcription, protein synthesis,
protein processing, and nitrogen and amino acid metabolisms, respectively.
CONCLUSIONS: WD promoted the CO2 assimilation by increase light reaction and
Calvin cycle, leading to the reprogramming of carbon metabolism. Moreover, the
accumulation of osmolytes (i.e., proline and total soluble sugar) and enhancement
of ascorbate-glutathione cycle and glutathione peroxidase/glutathione s
transferase pathway in leaves could minimize oxidative damage of membrane and
other molecules under WD. Importantly, the regulation role of carbohydrate
metabolisms (e. g. glycolysis, pentose phosphate pathways, and TCA) was enhanced.
These findings provide key candidate proteins for genetic improvement of
perennial plants metabolism under WD.
PMID- 28503102
TI - Transient Optical and Terahertz Spectroscopy of Nanoscale Films of RuO2.
AB - Solution-deposited nanoscale films of RuO2 ("nanoskins") are effective
transparent conductors once calcined to 200 degrees C. Upon heating the
nanoskins to higher temperature the nanoskins show increased transmission at 550
nm. Electronic microscopy and X-ray diffraction show that the changes in the
optical spectrum are accompanied by the formation of rutile RuO2 nanoparticles.
The mechanism for the spectral evolution is clearly observed with ultrafast
optical measurements. Following excitation at 400 nm, nanoskins calcined at
higher temperatures show increased transmission above 650 nm, consistent with the
photobleaching of a surface-plasmon resonance (SPR) band. Calculations based on
the optical constants of RuO2 substantiate the presence of SPR absorption. Sheet
resistance and transient terahertz photoconductivity measurements establish that
the nanoskins electrically de-wire into separated particles. The plasmonic
behavior of the nanoskins has implications their use in a range of optical and
electrochemical applications.
PMID- 28503103
TI - EDITORIAL: "The Faces of Mania: The Legacy of Athanasios Koukopoulos".
PMID- 28503104
TI - Introductory considerations Athanasios Koukopoulos: The Man, the Psychiatrist,
the Original Thinker.
PMID- 28503106
TI - Depression and Mania in Bipolar Disorder.
AB - BACKGROUND: Episode duration, recurrence rates, and time spent in manic and
depressive phases of bipolar disorder (BD) is not well defined for subtypes of
the disorder. METHODS: We reviewed the course, timing, and duration of episodes
of mania and depression among 1130 clinically treated DSM-IV-TR BD patients of
various types, and compared duration and rates as well as total proportion of
time in depressive versus manic episodes during 16.7 average years at risk.
RESULTS: As expected, episodes of depressions were much longer than manias, but
episode-duration did not differ among BD diagnostic types: I, II, with mainly
mixed-episodes (BD-Mx), or with psychotic features (BD-P). Recurrence rates
(episodes/year) and proportion of time in depression and their ratios to mania
were highest in BD-II and BD-Mx subjects, with more manias/year in psychotic and
BD-I subjects. In most BD-subtypes, except with psychotic features, there was
more time in depressive than manic morbidity, owing mainly to longer depressive
than manic episodes. The proportion of time in depression was highest among those
who followed a predominant DMI course, whereas total time in mania was greatest
in BD with psychotic features and BD-I. and with an MDI course. CONCLUSIONS:
Subtypes of BD patients differed little in episode-duration, which was
consistently much longer for depression. The findings underscore the limited
control of bipolar depression with available treatments.
PMID- 28503105
TI - Neurobiological Evidence for the Primacy of Mania Hypothesis.
AB - BACKGROUND: Athanasios Koukopoulos proposed the primacy of mania hypothesis (PoM)
in a 2006 book chapter and later, in two peer-reviewed papers with Nassir Ghaemi
and other collaborators. This hypothesis supports that in bipolar disorder, mania
leads to depression, while depression does not lead to mania. OBJECTIVE: To
identify evidence in literature that supports or falsifies this hypothesis.
METHOD: We searched the medical literature (PubMed, Embase, PsycINFO, and the
Cochrane Library) for peer-reviewed papers on the primacy of mania, the default
mode function of the brain in normal people and in bipolar disorder patients, and
on illusion superiority until 6 June, 2016. Papers resulting from searches were
considered for appropriateness to our objective. We adopted the PRISMA method for
our review. The search for consistency with PoM was filtered through the
neurobiological results of superiority illusion studies. RESULTS: Out of a grand
total of 139 records, 59 were included in our analysis. Of these, 36 were of
uncertain value as to the primacy of mania hypothesis, 22 favoured it, and 1 was
contrary, but the latter pooled patients in their manic and depressive phases, so
to invalidate possible conclusions about its consistency with regard to PoM. All
considered studies were not focused on PoM or superiority illusion, hence most of
their results were, as expected, unrelated to the circuitry involved in
superiority illusion. A considerable amount of evidence is consistent with the
hypothesis, although indirectly so. LIMITATIONS: Only few studies compared manic
with depressive phases, with the majority including patients in euthymia.
CONCLUSION: It is possible that humans have a natural tendency for
elation/optimism and positive self-consideration, that are more akin to mania;
the depressive state could be a consequence of frustrated or unsustainable mania.
This would be consistent with PoM.
PMID- 28503107
TI - The Role of Electroconvulsive Therapy (ECT) in Bipolar Disorder: Effectiveness in
522 Patients with Bipolar Depression, Mixed-state, Mania and Catatonic Features.
AB - OBJECTIVE: We evaluated the effectiveness of Electroconvulsive Therapy (ECT) in
the treatment of Bipolar Disorder (BD) in a large sample of bipolar patients with
drug resistant depression, mania, mixed state and catatonic features. METHOD: 522
consecutive patients with DSM-IV-TR BD were evaluated prior to and after the ECT
course. Responders and nonresponders were compared in subsamples of depressed and
mixed patients. Descriptive analyses were reported for patients with mania and
with catatonic features. RESULTS: Of the original sample only 22 patients were
excluded for the occurrence of side effects or consent withdrawal. After the ECT
course, 344 (68.8%) patients were considered responders (final CGIi score <=2)
and 156 (31.2%) nonresponders. Response rates were respectively 68.1% for BD
depression, 72.9% for mixed state, 75% for mania and 80.8% for catatonic
features. Length of current episode and global severity of the illness were the
only statistically significant predictors of nonresponse. CONCLUSION: ECT
resulted to be an effective and safe treatment for all the phases of severe and
drug-resistant BD. Positive response was observed in approximately two-thirds of
the cases and in 80% of the catatonic patients. The duration of the current
episode was the major predictor of nonresponse. The risk of ECT-induced mania is
virtually absent and mood destabilization very unlikely. Our results clearly
indicate that current algorithms for the treatment of depressive, mixed, manic
and catatonic states should be modified and, at least for the most severe
patients, ECT should not be considered as a "last resort".
PMID- 28503108
TI - Diagnosis and Treatment of Cyclothymia: The "Primacy" of Temperament.
AB - BACKGROUND: Contrary to DSM-5 definition based on recurrence of low grade
hypomanic and depressive symptoms, cyclothymia is better defined in a
neurodevelopmental perspective as an exaggeration of cyclothymic temperament.
Emotional dysregulation with extreme mood instability and reactivity is the core
features of the complex symptomatology. METHOD: In the present article, we
critically reviewed the literature on the diagnosis and treatment of cyclothymia,
focusing on the temperamental and neurodevelopmental perspectives. RESULTS:
Current epidemiological and clinical research showed the high prevalence and the
validity of cyclothymia as a distinct form of bipolarity, frequently associated
with multiple comorbidities with anxiety, impulse control, substance use, and so
called "personality" disorders. Many patients receive correct diagnosis and
treatments after many years of illness, when the superposition of complications
reduces the possibility of complete remission. A therapeutic model combining the
focus on symptomatic presentations with a temperamental perspective seems to
represent an effective approach for cyclothymic patients with complex clinical
presentations. CONCLUSION: Cyclothymic mood instability is an understudied issue
despite the evidence of its clinical relevance. Unresolved issues concern its
diagnostic delimitation and the possible relationships with emotional
dysregulation observed in other neurodevelopmental disorders. We need to confirm
the specificity of the disorder and to improve its recognition in early phase of
the life, especially in youth. Early recognition means avoiding unnecessary
complications and establishing specific treatments and clinical management since
the beginning.
PMID- 28503109
TI - Parental Reports of Prodromal Psychopathology in Pediatric Bipolar Disorder.
AB - OBJECTIVES: Early psychopathology in children diagnosed with Bipolar Disorder
(BD) remains poorly characterized. Parental retrospective reports provide helpful
details on the earliest manifestations and their evolution over time. These
symptoms occur early in the course of BD, often before a formal diagnosis is made
and/or treatment is implemented, and are of great importance to early recognition
and prevention. METHODS: Parents of pre-pubertal children and adolescents with
DSM-IV diagnoses of BD attending an outpatient mood disorders clinic provided
retrospective ratings of 37 symptoms of child psychopathology. Stability and
comorbidity of diagnoses were evaluated, and severity of symptoms for each
subject was assessed by identifying the earliest occurrence of the reported
symptoms causing impairment. RESULTS: Severe mood instability, temper tantrums,
anxiety symptoms, sleep disturbances and aggression were among the most common
signs of psychopathology reported in children diagnosed with BD before puberty.
Symptoms were already apparent in the first three years in 28%, and formal
diagnoses were made before the age of 8 y in the majority of cases. CONCLUSIONS:
Retrospective parental reports of early symptoms of psychopathology in pre
pubertal children with BD revealed a very early occurrence of affective
precursors (irritability and mood dysregulation) and clinical risk factors like
impulsive aggression and anxiety that can precede the syndromal onset of mania by
several years. These findings support previous reports suggesting a progression
of symptoms from abnormal, non-specific presentations to sub-threshold and
finally syndromal BD. The importance of early identification and intervention is
discussed.
PMID- 28503110
TI - Pediatric Mania: The Controversy between Euphoria and Irritability.
AB - Pediatric Bipolar Disorder (BD) is a highly morbid pediatric psychiatric disease,
consistently associated with family psychiatric history of mood disorders and
associated with high levels of morbidity and disability and with a great risk of
suicide. While there is a general consensus on the symptomatology of depression
in childhood, the phenomenology of pediatric mania is still highly debated and
the course and long-term outcome of pediatric BD still need to be clarified. We
reviewed the available studies on the phenomenology of pediatric mania with the
aim of summarizing the prevalence, demographics, clinical correlates and course
of these two types of pediatric mania. Eighteen studies reported the number of
subjects presenting with either irritable or elated mood during mania.
Irritability has been reported to be the most frequent clinical feature of
pediatric mania reaching a sensitivity of 95-100% in several samples. Only half
the studies reviewed reported on number of episodes or cycling patterns and the
described course was mostly chronic and ultra-rapid whereas the classical
episodic presentation was less common. Few long-term outcome studies have
reported a diagnostic stability of mania from childhood to young adult age.
Future research should focus on the heterogeneity of irritability aiming at
differentiating distinct subtypes of pediatric psychiatric disorders with
distinct phenomenology, course, outcome and biomarkers. Longitudinal studies of
samples attending to mood presentation, irritable versus elated, and course,
chronic versus episodic, may help clarify whether these are meaningful
distinctions in the course, treatment and outcome of pediatric onset bipolar
disorder.
PMID- 28503111
TI - Free Interval Duration: Clinical Evidence of the Primary Role of Excitement in
Bipolar Disorder.
AB - BACKGROUND: Cyclicity is the essential feature of Bipolar disorder, but the
effect of different cycle patterns on the clinical features is poorly understood.
Moreover, no studies investigated the relationship between mania and depression
inside the manic-depressive cycle. OBJECTIVE: The aim of this study is to verify
the presence of a relationship between the manic and the depressive phase during
the course of bipolar disorder. METHOD: 160 consecutive patients with BD type I
were recruited and followed for a mean period of 10 years. During the follow-up
period, four types of euthymic phases were collected: free intervals present
between a depressive and a manic/hypomanic episode (D-M); free intervals present
between a manic/hypomanic and a depressive episode (M-D); free intervals present
between two depressive episodes (D-D); free intervals present between two
manic/hypomanic episodes (M-M). One-way ANOVA using the groups as independent
variable and the duration of the free intervals as dependent variables was used.
Furthermore, ANOVA was followed by Fisher's Protected Least Significant
Difference post-hoc test to measure between-group differences. RESULTS: M-D-free
interval phases were shorter than D-M-free intervals. M-D intervals were the
shortest ones, the D-D and D-M did not differ, and the M-M were the longest.
CONCLUSION: The strict temporal link between manic and depressive phases supports
the idea that the manic-depressive cycle usually begins with a manic episode, and
that the subsequent depression is often the consequence of subsiding mania.
PMID- 28503112
TI - Athanasios Koukopoulos' Psychiatry: The Primacy of Mania and the Limits of
Antidepressants.
AB - BACKGROUND: Athanasios Koukopoulos provided a radical model for understanding
depressive and manic conditions. OBJECTIVE: To review, explain, and analyze
Koukopoulos' concept of the primacy of mania, with special attention to the role
of antidepressants. METHOD: A conceptual review of Koukopoulos' writings and
lectures on this topic is given. RESULTS: Koukopoulos held that depressive states
are caused by manic states; the former do not occur without the latter. The most
common scenario of the inseparability of depressive and manic symptoms occurs in
mixed states, which we estimate to represent about one-half of all depressive
episodes in all patients (not just bipolar illness). In a review of the empirical
evidence for this topic, we conclude that empirical evidence exists to support
the primary of mania thesis in almost 80% of depressed patients. Since
antidepressants worsen mania, they would be expected to worsen depression as well
in this model. We provide evidence that supports this view in most persons with
depressive states. CONCLUSION: Koukopoulos' model of affective illness is one
where manic states are the primary pathology, and depressive conditions are a
secondary consequence. Hence treatment of depression with antidepressants would
be less effective than treatment with mood stabilizers, since treating an effect
is less successful than treating its cause. This approach would reverse current
assumptions in psychiatry.
PMID- 28503113
TI - Who's the Leader, Mania or Depression? Predominant Polarity and
Alcohol/Polysubstance Use in Bipolar Disorders.
AB - BACKGROUND: Predominant polarity characterises patients who mainly manifest
recurrences of depression or mania/hypomania. Alcohol use disorder (AUD) and
polysubstance use (PSU), which often complicate bipolar disorder (BD) and affect
its clinical course, can influence predominant polarity. Nevertheless, previous
studies have not clarified if BD patients differ in predominant polarity from BD
patients with substance use disorder (SUD) comorbidity. OBJECTIVE: The aim of
this study was to compare predominant polarity between BD without SUD, BD with
AUD and BD with PSU. We also investigated the association between predominant
polarity and first episode polarity in each diagnostic group. METHOD: We
evaluated predominant polarity (>=2:1 lifetime depressive vs. manic/hypomanic
episodes) in 218 DSM-IV-TR BD patients. Specifically, data were obtained from 86
patients with BD without SUD, 69 patients with BD and AUD, and 63 patients with
BD and PSU with alcohol as the primary substance abused. RESULTS: The three
groups significantly differed for predominant polarity. The most common
predominant polarity in BD without SUD was manic, while in BD with AUD and in BD
with PSU it was depressive. Uncertain predominant polarity was the least common
in BD without SUD and BD with PSU, whereas in BD with AUD, manic predominant
polarity was least common. Predominant polarity matched onset polarity in all
groups. CONCLUSION: BD without SUD, BD with AUD, and BD with PSU have different
predominant polarities. The correspondence between predominant polarity and
polarity at the onset may impact diagnosis and treatment of BD.
PMID- 28503114
TI - Antidepressant-induced Dopamine Receptor Dysregulation: A Valid Animal Model of
Manic-Depressive Illness.
AB - BACKGROUND: Mania seems to be associated with an increased dopamine (DA)
transmission. Antidepressant treatments can induce mania in humans and
potentiated DA transmission in animals, by sensitizing DA D2 receptors in the
mesolimbic system. We have suggested that the sensitization of D2 receptors may
be responsible of antidepressant-induced mania. This review aims to report the
experimental evidence that led to the hypothesis that antidepressant-induced DA
receptors dysregulation can be considered an animal model of bipolar disorder.
METHODS: We reviewed papers reporting preclinical and clinical studies on the
role of DA in the mechanism of action of antidepressant treatments and in the
patho-physiology of mood disorders. RESULTS: A number of preclinical and clinical
evidence suggests that mania could be associated with an increased DA activity,
while a reduced function of this neurotransmission might underlie depression.
Chronic treatment with imipramine induces a sensitization of DA D2 receptors in
the mesolimbic system, followed, after drug discontinuation, by a reduced
sensitivity associated with an increased immobility time in forced swimming test
of depression (FST). Blockade of glutamate NMDA receptors by memantine
administration prevents the imipramine effect on DA receptors sensitivity and on
the FST. CONCLUSION: We suggest that chronic treatment with antidepressants
induces a behavioural syndrome that mimics mania (the sensitization of DA
receptors), followed by depression (desensitization of DA receptors and increased
immobility time in the FST), i.e. an animal model of bipolar disorder. Moreover
the observation that memantine prevents the "bipolar-like" behavior, suggests
that the drug may have an antimanic and mood stabilizing effect. Preliminary
clinical observations support this hypothesis.
PMID- 28503115
TI - Is Mania the Hypertension of the Mood? Discussion of A Hypothesis.
AB - Beyond both being biphasic/bidirectional disorders (hypo)mania and essential
hypertension share a surprising number of similarities and an overlap between
their genetics, biological background, underlying personality and temperamental
factors, precipitating factors, comorbidity and response to treatment, indicating
a possibly partially shared biological background. Based on theoretical
knowledge, similarities related to characteristics, manifestation and course, and
the results of pharmacological studies related to the effects and side effects of
pharmacotherapies used in the treatment of these two distinct disorders, the
authors outline a hypothesis discussing the similar origins of these two
phenomena and thus mania being the hypertension of mood in memory of Athanasios
Koukopoulos, one of the greatest researchers and theoreticists of mania of all
time.
PMID- 28503118
TI - An Additional Method for Analyzing the Reversible Inhibition of an ?Enzyme Using
Acid Phosphatase as a Model.
AB - Using wheat germ acid phosphatase and sodium orthovanadate as a competitive
inhibitor, a novel method for analyzing reversible inhibition was carried out.
Our alternative approach involves plotting the initial velocity at which product
is formed as a function of the ratio of substrate concentration to inhibitor
concentration at a constant enzyme concentration and constant assay conditions.
The concept of initial concentrations driving equilibrium leads to the chosen
axes. Three apparent constants can be derived from this plot: Kmax, Kmin, and
Kinflect. Kmax and Kmin represent the substrate to inhibitor concentration ratio
for complete inhibition and minimal inhibition, respectively. Kinflect represents
the substrate to inhibitor concentration ratio at which the enzyme-substrate
complex is equal to the inhibitory complex. These constants can be interpolated
from the graph or calculated using the first and second derivative of the plot.
We conclude that a steeper slope and a shift of the line to the right (increased
x-axis values) would indicate a better inhibitor. Since initial velocity is not a
linear function of the substrate/inhibitor ratio, this means that inhibition
changes more quickly with the change in the [S]/ [I] ratio. When preincubating
the enzyme with substrate before the addition of inhibitor, preincubating the
enzyme with inhibitor before the addition of substrate or with concurrent
addition of both substrate and inhibitor, modest changes in the slopes and y
intercepts were obtained. This plot appears useful for known competitive and non
competitive inhibitors and may have general applicability.
PMID- 28503119
TI - Targeting HIV-1 Envelope Proteins Using a Fragment Discovery All-Atom
Computational Algorithm.
AB - INTRODUCTION: HIV viral envelope proteins are targets for small inhibitor
molecules aimed at disrupting the cellular entry process. Potential peptide-class
inhibitor molecules (rDNA drugs) have been previously identified, with mixed
results, through biomimicry and phage display experimental methods. Here we
describe a new approach based on computational fragment discovery. The method has
the potential to not only optimize peptide binding affinity but also to rapidly
produce alternative inhibitors against mutated strains. METHODS: A comprehensive,
all-atom implicit solvent method is used to bombard the C-heptad repeat unit of
HIV-1 target envelope protein GP41 with single D-amino acid residues as they
exist in their native state. A nascent peptide computational search process then
identifies potential favorable sequences of attached ligands based on four
peptide bond criteria. Finally, dynamic simulations of nascent peptides attached
to host targets help refine potential peptide inhibitors for experimental HIV-1
challenge assays and testing. RESULTS AND DISCUSSION: Initial testing of the
method was done using 64,000 total ligands of D-amino acid residues at a total
computational time of 0.05 microseconds per ligand, which resulted in several
thousand attached ligands. Peptide bond criteria search employing three of the
four bond constraints with a tolerance of 20 percent, resulted in four potential
peptide inhibitors of 5 to 6 residues in length. Only one of the four peptides
demonstrated IC50 values and partial viral inhibition based on cell challenge
assays using CEM-SS host cells. That peptide inhibitor also computationally
demonstrated long-time attachment and stability to a helical groove in its C
heptad target. This initial testing of peptide fragment discovery against HIV-1
has helped us refine the protocols and identify key areas of improvement.
CONCLUSION: Our methods demonstrate the potential to design efficient peptide
inhibitors to viral target proteins based on an all-atom dynamic simulation and
using a ligand library as fragments of potential nascent peptides. Our methods
can be greatly improved through the use of higher numbers of ligands, increased
time of bombardment, and tighter constraints on the peptide bond search step. Our
method may be important in the need to rapidly respond to target mutations and to
advance multiple targeting methods based multiple peptide inhibitors.
PMID- 28503121
TI - Hemostasis and Hemotherapy.
PMID- 28503116
TI - Melatonin: Pharmacology, Functions and Therapeutic Benefits.
AB - BACKGROUND: Melatonin synchronizes central but also peripheral oscillators (fetal
adrenal gland, pancreas, liver, kidney, heart, lung, fat, gut, etc.), allowing
temporal organization of biological functions through circadian rhythms (24-hour
cycles) in relation to periodic environmental changes and therefore adaptation of
the individual to his/her internal and external environment. Measures of
melatonin are considered the best peripheral indices of human circadian timing
based on an internal 24-hour clock. METHODS: First, the pharmacology of melatonin
(biosynthesis and circadian rhythms, pharmacokinetics and mechanisms of action)
is described, allowing a better understanding of the short and long term effects
of melatonin following its immediate or prolonged release. Then, research related
to the physiological effects of melatonin is reviewed. RESULTS: The physiological
effects of melatonin are various and include detoxification of free radicals and
antioxidant actions, bone formation and protection, reproduction, and
cardiovascular, immune or body mass regulation. Also, protective and therapeutic
effects of melatonin are reported, especially with regard to brain or
gastrointestinal protection, psychiatric disorders, cardiovascular diseases and
oncostatic effects. CONCLUSION: This review highlights the high number and
diversity of major melatonin effects and opens important perspectives for
measuring melatonin as a biomarker (biomarker of early identification of certain
disorders and also biomarker of their follow-up) and using melatonin with
clinical preventive and therapeutic applications in newborns, children and adults
based on its physiological regulatory effects.
PMID- 28503120
TI - A two-week pilot study of intranasal oxytocin for cocaine-dependent individuals
receiving methadone maintenance treatment for opioid use disorder.
AB - 30-60% of patients receiving methadone for opioid use disorder (OUD) actively use
cocaine. Cocaine use disorder (CUD) has no FDA-approved pharmacological
treatment; existing psychosocial treatments are inadequate. Oxytocin, a social
neuropeptide, has preclinical promise as an adjunctive treatment for both OUD and
CUD. Twenty-two individuals receiving methadone for OUD with co-occurring CUD
were randomized to receive oxytocin or placebo intranasally 40 IU twice daily for
two weeks. A priori aims were feasibility and safety. Exploratory effectiveness
aims included laboratory-based measures of drug craving, drug-related implicit
cognition, and drug use. High retention rates (93.5%), the absence of study
related adverse events, and the fact that oxytocin was well tolerated in this
population support the feasibility of larger trials. Two weeks of oxytocin (but
not placebo) significantly reduced cocaine craving at day 15 compared to baseline
(mean change+/-SD: OT=-0.23+/-0.19, p=0.004; PL=-0.16+/-0.29, p=0.114). For
heroin craving, the placebo group reported a trend-level increase over time while
the oxytocin group remained unchanged - with medium to large effect sizes between
the groups (Cohen's d=0.71-0.90). Oxytocin led to a significant switch from
implicit self-association with drugs to implicitly associating drugs with others
(mean change+/-SD: 0.25+/-0.35, p=0.037) and a trend-level reduction in self
reported cocaine use over time (Z=-1.78, p=0.075). Furthermore, oxytocin
significantly increased the accuracy of self-reported cocaine use when correlated
with quantitative urine levels of cocaine metabolite. This proof-of-concept study
provides promising early evidence that oxytocin may be an effective adjunct to
the treatment of co-occurring CUD and OUD. Further investigation with larger
trials is warranted.
PMID- 28503117
TI - Opioids Resistance in Chronic Pain Management.
AB - Chronic pain management represents a serious healthcare problem worldwide.
Chronic pain affects approximately 20% of the adult European population and is
more frequent in women and older people. Unfortunately, its management in the
community remains generally unsatisfactory and rarely under the control of
currently available analgesics. Opioids have been used as analgesics for a long
history and are among the most used drugs; however, while there is no debate over
their short term use for pain management, limited evidence supports their
efficacy of long-term treatment for chronic non-cancer pain. Therapy with opioids
is hampered by inter-individual variability and serious side effects and some
opioids often result ineffective in the treatment of chronic pain and their use
is controversial. Accordingly, for a better control of chronic pain a deeper
knowledge of the molecular mechanisms underlying resistance to opiates is
mandatory.
PMID- 28503122
TI - Thrombosis in Inherited Fibrinogen Disorders.
AB - Although inherited fibrinogen disorders (IFD) are primarily considered to be
bleeding disorders, they are associated with a higher thrombotic complication
risk than defects in other clotting factors. Managing IFD patients with
thrombosis is challenging as anticoagulant treatment may exacerbate the
underlying bleeding risk which can be life-threatening. Due to the low prevalence
of IFD, there is little information on pathophysiology or optimal treatment of
thrombosis in these patients. We searched the literature for cases of thrombosis
among IFD patients and identified a total of 128 patient reports. In
approximately half of the cases, thromboses were spontaneous, while in the others
trauma, surgery, and parturition contributed to the risk. The true mechanism(s)
of thrombosis in IFD patients remain to be elucidated. A variety of anticoagulant
treatments have been used in the treatment or prevention of thrombosis, sometimes
with concurrent fibrinogen replacement therapy. There is no definite evidence
that fibrinogen supplementation increases the risk of thrombosis, and it may
potentially be effective in the treatment and prevention of both thrombosis and
hemorrhage in IFD patients.
PMID- 28503123
TI - Thromboelastometry and Thrombelastography Analysis under Normal Physiological
Conditions - Systematic Review.
AB - BACKGROUND: Studies investigating thromboelastometry or thrombelastography
analyses in a physiological context are scattered and not easy to access.
OBJECTIVE: To systematically retrieve and describe published reports studying
healthy subjects and targeting at the correlation of ROTEM(r) and TEG(r)
measurements with conventional parameters of hemostasis. METHODS: Systematic
Review: Papers were searched in Medline, Scopus and the Science Citation Index
database. Reference lists of included studies and of reviews were screened. To be
included papers had to report ROTEM or TEG data on healthy subjects. Two
reviewers screened papers for inclusion, read full texts of potentially relevant
papers, and extracted data of included papers. RESULTS: Searches identified 1,721
records of which 1,713 were either excluded immediately or after reading the full
text. The remaining 8 studies enrolled 632 subjects. The association of
conventional parameters of hemostasis with ROTEM and with TEG was investigated in
one and two studies, respectively. Overall correlation was limited and ranged
from 0.0 to 0.40 (total thrombus generation vs. fibrinogen; clotting time INTEM
vs. activated partial thromboplastin time). CONCLUSIONS: Studies assessing the
relationship between thromboelastometry or thromboelastography analyses and
conventional parameters of hemostasis in healthy subjects remains scarce, and
correlations are limited. Further research is needed to understand the physiology
of thromboelastometry and thromboelastography parameters.
PMID- 28503125
TI - Thawing of Pooled, Solvent/Detergent-Treated Plasma octaplasLG(r): Validation
Studies Using Different Thawing Devices.
AB - BACKGROUND: The aim of this study was to perform validation of the thawing
process for solvent/detergent-treated plasma octaplasLG(r) using different
thawing devices. Optimized settings for temperature and thawing time should be
defined based on the results of both temperature measurements and extensive
biochemical characterization studies. METHODS: octaplasLG units were thawed using
water bath systems (i.e. MB-13A, QuickThaw(r) DH4), dry tempering systems (i.e.
plasmatherm, SAHARA-III), and microwave oven (i.e. transfusio-therm(r) 2000).
Optimized thawing conditions were defined. Subsequently, using the selected
thawing conditions, octaplasLG units were thawed and tested on product release
parameters. RESULTS: The fastest thawing was observed for the microwave oven. All
octaplasLG units thawed by different devices and optimized thawing conditions
were clear and free of solid and gelatinous particles, indicating no protein
denaturation or overheating. In addition, no significant differences were found
in the coagulation and inhibition activity and hemostatic potency of octaplasLG
when thawed by the different devices tested. All parameters after thawing were
within the product release specification levels. CONCLUSION: Our study
demonstrated that octaplasLG can be thawed using all above listed devices without
any negative influence on the plasma quality, presupposed that optimized settings
defined for this plasma product are used.
PMID- 28503126
TI - In vitro and ex vivo Measurement of Prophylactic Dabigatran Concentrations with a
New Ecarin-Based Thromboelastometry Test.
AB - BACKGROUND: An increasing number of oral anticoagulants has been approved,
including dabigatran etexilate (DE). DE is a direct thrombin inhibitor that
requires no routine monitoring, but, if necessary (e.g. urgent surgery etc.), the
diluted thrombin time measured with Hemoclot(r) has shown reliable results. So
far, no point-of-care (PoC) assay is available to measure DE effects. The EcaTEM
assay uses ecarin to initiate the coagulation cascade at the step of thrombin
generation and measures the clotting time (CT) by thromboelastometry. METHODS:
This study investigated the correlation of the EcaTEM with standard laboratory
assays in dabigatran-treated patients. Ten patients undergoing total hip or knee
arthroplasty were included in the study. DE for thromboprophylaxis was started 4
h after surgery. Blood samples were taken before surgery as well as 2, 6 and 12 h
after ingestion on the 3rd postoperative day. Dabigatran concentration
(Hemoclot), activated partial thromboplastin time, thrombin time and CT EcaTEM
were measured. RESULTS: Only CT EcaTEM and Hemoclot showed a correlation > 0.75
for all measurements. CONCLUSION: CT EcaTEM appears a valid PoC method parameter
to detect thrombin inhibition and thus the presence of dabigatran beside diluted
thrombin time at different concentration levels. This may represent an
opportunity to identify the presence of dabigatran, e.g., in emergency
situations.
PMID- 28503124
TI - Factor XIII Deficiency and Thrombocytopenia Are Frequent Modulators of
Postoperative Clot Firmness in a Surgical Intensive Care Unit.
AB - OBJECTIVE: Fibrinogen and factor XIII (FXIII) have been shown to critically
influence clot firmness in the intraoperative setting and thus likely influence
intraoperative bleeding. We were interested to identify potential modulators of
postoperative clot firmness in a tertiary care hospital surgical intensive care
unit setting, independent of their clinical course during surgery. METHODS: 272
day-shift consecutive patients were evaluated for whole blood clot firmness
evaluated by the ROTEM(r) EXTEM thrombelastometric assay and various potential
modulators of clot firmness upon arrival at the surgical intensive care unit
(SICU). RESULTS: Maximum clot firmness on the SICU was found to be independently
influenced by the amount of colloids given during surgery as well as by platelet
count, fibrinogen concentration, and FXIII activity at the time of SICU
admission. In patients with lowest clot firmness, FXIII activity was the most
important independent modulator of clot firmness; in patients with the highest
clot firmness, platelet count and fibrinogen concentration were the most
important modulators of clot firmness. Deficiencies (i.e., results below normal
range) of these modulators of clot firmness were most prevalent for FXIII
(activity < 70%: 45% of cases), which was significantly more frequent than
thrombocytopenia (<150 * 109/l: 32%) or fibrinogen deficiency (<1.5 g/l: 6%).
CONCLUSIONS: Postoperative clot firmness as evaluated by whole blood
thrombelastometry (ROTEM EXTEM assay) is independently and frequently modulated
though FXIII activity and the platelet count, while fibrinogen concentration is
also an independent but much less frequent modulator. Different modulators show
different influences, depending on the clot firmness being present. Colloids
infused during surgery also independently modulate postoperative clot firmness.
Based on our data, strategies can be developed to improving postoperative care of
patients with bleedings or at risk for bleeding.
PMID- 28503127
TI - The Role of Platelet Function Analyzer Testing in Cardiac Surgery Transfusion
Management.
AB - BACKGROUND: Identifying high-risk patients for transfusion after cardiac
operations would alter postoperative management. The aim of this study was to
investigate closure time (CT) measured by platelet function analyzer (PFA) for
prediction of bleeding and transfusions. METHODS: 66 patients were scheduled for
coronary artery bypass graft (CABG) surgery and 30 patients for valve repair and
replacement (non-CABG). Measurements of PFA-100(r) CT for collagen and adenosine
diphosphate (cADP) and collagen and epinephrine (cEPI) were performed 15 min
after protamine administration. Blood loss was measured, and the amount of
transfusion products was recorded postoperatively. RESULTS: The study
demonstrated significant differences between CABG patients with cADP-CT >= 118 s
and those with cADP-CT < 118 s with regard to blood loss for 24 h (p = 0.001) and
blood loss for 25-48 h (p = 0.003) as well as fresh frozen plasma (p = 0.015),
platelet (p > 0.001) and red blood cell (p = 0.002) units given in 48
postoperative h. There were no differences cardiopulmonary bypass when was
applied. In non-CABG patients, there were no differences in blood loss and
transfusion requirements with respect to cADP-CT and cEPI-CT. CONCLUSION:
Postoperative platelet dysfunction measured by a prolonged cADP-CT was
significant predictor of blood loss and transfusion in CABG patients.
PMID- 28503128
TI - A Confounding Case of Inherited Factor V Deficiency Complicated by Inhibitors at
First Presentation.
AB - INTRODUCTION: Inherited factor V deficiency / Owren's disease has varied clinical
manifestations ranging from asymptomatic laboratory abnormalities to massive
hemorrhage. The acquired form due to inhibitors following antibiotic therapy,
infection, or surgery is less common, and spontaneous development of inhibitors
is not known. CASE REPORT: An 18-year-old boy presented with bleeding axillary
and groin ulcers. At the age of 15, due to recurrent epistaxis and gum bleed, he
was diagnosed with acquired factor V deficiency with positive inhibitor screen
and treated with fresh frozen plasma (FFP) transfusion and temporary
azathioprine. Coagulation workup at his current presentation also revealed
acquired factor V deficiency with presence of inhibitors. The tests were repeated
after 6 weeks of intermittent FFP transfusion, and the differences observed
included negative inhibitor screen and complete correction on mixing studies, but
factor V level was 2%. DISCUSSION: Evidence of inhibitors at presentation favored
acquired disease. However, younger age of onset, detection of inhibitors 1 year
after first episode of self-regressing bleed, lack of identifiable triggers, and
persistent bleeding with reduced factor levels after disappearance of inhibitors
favored inherited factor V deficiency. CONCLUSION: In this case report, we have
described an interesting case of severe inherited factor V deficiency with
spontaneous appearance and disappearance of inhibitors exhibiting nonspecific
factor inhibitory activity.
PMID- 28503129
TI - Pathophysiology, Diagnosis and Treatment of Somatosensory Tinnitus: A Scoping
Review.
AB - Somatosensory tinnitus is a generally agreed subtype of tinnitus that is
associated with activation of the somatosensory, somatomotor, and visual-motor
systems. A key characteristic of somatosensory tinnitus is that is modulated by
physical contact or movement. Although it seems common, its pathophysiology,
assessment and treatment are not well defined. We present a scoping review on the
pathophysiology, diagnosis, and treatment of somatosensory tinnitus, and identify
priority directions for further research. Methods: Literature searches were
conducted in Google Scholar, PubMed, and EMBASE databases. Additional broad hand
searches were conducted with the additional terms etiology, diagnose, treatment.
Results: Most evidence on the pathophysiology of somatosensory tinnitus suggests
that somatic modulations are the result of altered or cross-modal synaptic
activity within the dorsal cochlear nucleus or between the auditory nervous
system and other sensory subsystems of central nervous system (e.g., visual or
tactile). Presentations of somatosensory tinnitus are varied and evidence for the
various approaches to treatment promising but limited. Discussion and
Conclusions: Despite the apparent prevalence of somatosensory tinnitus its
underlying neural processes are still not well understood. Necessary involvement
of multidisciplinary teams in its diagnosis and treatment has led to a large
heterogeneity of approaches whereby tinnitus improvement is often only a
secondary effect. Hence there are no evidence-based clinical guidelines, and
patient care is empirical rather than research-evidence-based. Somatic testing
should receive further attention considering the breath of evidence on the
ability of patients to modulate their tinnitus through manouvers. Specific
questions for further research and review are indicated.
PMID- 28503131
TI - Editorial: Myelin-Mediated Inhibition of Axonal Regeneration: Past, Present, and
Future.
PMID- 28503130
TI - Uncoupling the Trade-Off between Somatic Proteostasis and Reproduction in
Caenorhabditis elegans Models of Polyglutamine Diseases.
AB - Caenorhabditis elegans somatic protein homeostasis (proteostasis) is actively
remodeled at the onset of reproduction. This proteostatic collapse is regulated
cell-nonautonomously by signals from the reproductive system that transmit the
commitment to reproduction to somatic cells. Here, we asked whether the link
between the reproductive system and somatic proteostasis could be uncoupled by
activating downstream effectors in the gonadal longevity cascade. Specifically,
we examined whether over-expression of lipl-4 (lipl-4(oe)), a target gene of the
gonadal longevity pathway, or increase in arachidonic acid (AA) levels,
associated with lipl-4(oe), modulated proteostasis and reproduction. We found
that lipl-4(oe) rescued somatic proteostasis and postponed the onset of
aggregation and toxicity in C. elegans models of polyglutamine (polyQ) diseases.
However, lipl-4(oe) also disrupted fatty acid transport into developing oocytes
and reduced reproductive success. In contrast, diet supplementation of AA
recapitulated lipl-4(oe)-mediated proteostasis enhancement in wild type animals
but did not affect the reproductive system. Thus, the gonadal longevity pathway
mediates a trade-off between somatic maintenance and reproduction, in part by
regulating the expression of genes, such as lipl-4, with inverse effects on
somatic maintenance and reproduction. We propose that AA could uncouple such
germline to soma crosstalk, with beneficial implications protein misfolding
diseases.
PMID- 28503132
TI - Protecting Mammalian Hair Cells from Aminoglycoside-Toxicity: Assessing
Phenoxybenzamine's Potential.
AB - Aminoglycosides (AGs) are widely used antibiotics because of their low cost and
high efficacy against gram-negative bacterial infection. However, AGs are
ototoxic, causing the death of sensory hair cells in the inner ear. Strategies
aimed at developing or discovering agents that protect against aminoglycoside
ototoxicity have focused on inhibiting apoptosis or more recently, on preventing
antibiotic uptake by the hair cells. Recent screens for ototoprotective compounds
using the larval zebrafish lateral line identified phenoxybenzamine as a
potential protectant for aminoglycoside-induced hair cell death. Here we used
live imaging of FM1-43 uptake as a proxy for aminoglycoside entry, combined with
hair-cell death assays to evaluate whether phenoxybenzamine can protect mammalian
cochlear hair cells from the deleterious effects of the aminoglycoside antibiotic
neomycin. We show that phenoxybenzamine can block FM1-43 entry into mammalian
hair cells in a reversible and dose-dependent manner, but pre-incubation is
required for maximal inhibition of entry. We observed differential effects of
phenoxybenzamine on FM1-43 uptake in the two different types of cochlear hair
cell in mammals, the outer hair cells (OHCs) and inner hair cells (IHCs). The
requirement for pre-incubation and reversibility suggests an intracellular rather
than an extracellular site of action for phenoxybenzamine. We also tested the
efficacy of phenoxybenzamine as an otoprotective agent. In mouse cochlear
explants the hair cell death resulting from 24 h exposure to neomycin was steeply
dose-dependent, with 50% cell death occurring at ~230 MUM for both IHC and OHC.
We used 250 MUM neomycin in subsequent hair-cell death assays. At 100 MUM with 1
h pre-incubation, phenoxybenzamine conferred significant protection to both IHCs
and OHCs, however at higher concentrations phenoxybenzamine itself showed clear
signs of ototoxicity and an additive toxic effect when combined with neomycin.
These data do not support the use of phenoxybenzamine as a therapeutic agent in
mammalian inner ear. Our findings do share parallels with the observations from
the zebrafish lateral line model but they also highlight the necessity for
validation in the mammalian system and the potential for differential effects on
sensory hair cells from different species, in different systems and even between
cells in the same organ.
PMID- 28503133
TI - Behavioral Senescence and Aging-Related Changes in Motor Neurons and Brain
Neuromodulator Levels Are Ameliorated by Lifespan-Extending Reproductive Dormancy
in Drosophila.
AB - The lifespan of Drosophilamelanogaster can be extended substantially by inducing
reproductive dormancy (also known as diapause) by lowered temperature and short
days. This increase of longevity is accompanied by lowered metabolism and
increased stress tolerance. We ask here whether behavioral senescence is
ameliorated during adult dormancy. To study this we kept flies for seven or more
weeks in normal rearing conditions or in diapause conditions and compared to 1
week-old flies in different behavioral assays of sleep, negative geotaxis and
exploratory walking. We found that the senescence of geotaxis and locomotor
behavior seen under normal rearing conditions was negligible in flies kept in
dormancy. The normal senescence of rhythmic activity and sleep patterns during
the daytime was also reduced by adult dormancy. Investigating the morphology of
specific neuromuscular junctions (NMJs), we found that changes normally seen with
aging do not take place in dormant flies. To monitor age-associated changes in
neuronal circuits regulating activity rhythms, sleep and walking behavior we
applied antisera to tyrosine hydroxylase (TH), serotonin and several
neuropeptides to examine changes in expression levels and neuron morphology. In
most neuron types the levels of stored neuromodulators decreased during normal
aging, but not in diapause treated flies. No signs of neurodegeneration were seen
in either condition. Our data suggest that age-related changes in motor neurons
could be the cause of part of the behavioral senescence and that this is
ameliorated by reproductive diapause. Earlier studies established a link between
age-associated decreases in neuromodulator levels and behavioral decline that
could be rescued by overexpression of neuromodulator. Thus, it is likely that the
retained levels of neuromodulators in dormant flies alleviate behavioral
senescence.
PMID- 28503134
TI - Aquaporin 4-Mediated Glutamate-Induced Astrocyte Swelling Is Partially Mediated
through Metabotropic Glutamate Receptor 5 Activation.
AB - Astrocytes are one of the most abundant cell types in the mammalian central
nervous system (CNS), and astrocyte swelling is the primary event associated with
brain edema. Glutamate, the principal excitatory amino acid neurotransmitter in
the CNS, is released at high levels after brain injury including cerebral
ischemia. This leads to astrocyte swelling, which we previously demonstrated is
related to metabotropic glutamate receptor (mGluR) activation. Aquaporin 4
(AQP4), the predominant water channel in the brain, is expressed in astrocyte
endfeet and plays an important role in brain edema following ischemia. Studies
recently showed that mGluR5 is also expressed on astrocytes. Therefore, it is
worth investigating whether AQP4 mediates the glutamate-induced swelling of
astrocytes via mGluR5. In the present study, we found that 1 mM glutamate induced
astrocyte swelling, quantified by the cell perimeter, but it had no effect on
astrocyte viability measured by the cell counting kit-8 (CCK-8) and lactate
dehydrogenase (LDH) assays. Quantitative reverse transcription polymerase chain
reaction analyses revealed that AQP4, among AQP1, 4, 5, 9 and 11, was the main
molecular expressed in cultured astrocytes. Glutamate-induced cell swelling was
accompanied by a concentration-dependent change in AQP4 expression. Furthermore,
RNAi technology revealed that AQP4 gene silencing inhibited glutamate-induced
astrocyte swelling. Moreover, we found that mGluR5 expression was greatest among
the mGluRs in cultured astrocytes and was co-expressed with AQP4. Activation of
mGluR5 in cultured astrocytes using (S)-3,5-dihydroxyphenylglycine (DHPG), an
mGluR5 agonist, mimicked the effect of glutamate. This effect was abolished by co
incubation with the mGluR5 antagonist fenobam but was not influenced by DL-threo
beta-benzyloxyaspartic acid (DL-TBOA), a glutamate transporter inhibitor.
Finally, experiments in a rat model of transient middle cerebral artery occlusion
(tMCAO) revealed that co-expression of mGluR5 and AQP4 was increased in astrocyte
endfeet around capillaries in the penumbra, and this was accompanied by brain
edema. Collectively, these results suggest that glutamate induces cell swelling
and alters AQP4 expression in astrocytes via mGluR5 activation, which may provide
a novel approach for the treatment of edema following brain injury.
PMID- 28503136
TI - A Quantitative Golgi Study of Dendritic Morphology in the Mice Striatal Medium
Spiny Neurons.
AB - In this study we have provided a detailed quantitative morphological analysis of
medium spiny neurons (MSNs) in the mice dorsal striatum and determined the
consistency of values among three groups of animals obtained in different set of
experiments. Dendritic trees of 162 Golgi Cox (FD Rapid GolgiStain Kit)
impregnated MSNs from 15 adult C57BL/6 mice were 3-dimensionally reconstructed
using Neurolucida software, and parameters of dendritic morphology have been
compared among experimental groups. The parameters of length and branching
pattern did not show statistically significant difference and were highly
consistent among groups. The average neuronal soma surface was between 160 MUm2
and 180 MUm2, and the cells had 5-6 primary dendrites with close to 40 segments
per neuron. Sholl analysis confirmed regular pattern of dendritic branching. The
total length of dendrites was around 2100 MUm with the average length of
individual branching (intermediate) segment around 22 MUm and for the terminal
segment around 100 MUm. Even though each experimental group underwent the same
strictly defined protocol in tissue preparation and Golgi staining, we found
inconsistency in dendritic volume and soma surface. These changes could be
methodologically influenced during the Golgi procedure, although without
affecting the dendritic length and tree complexity. Since the neuronal activity
affects the dendritic thickness, it could not be excluded that observed volume
inconsistency was related with functional states of neurons prior to animal
sacrifice. Comprehensive analyses of tree complexity and dendritic length
provided here could serve as an additional tool for understanding morphological
variability in the most numerous neuronal population of the striatum. As
reference values they could provide basic ground for comparisons with the results
obtained in studies that use various models of genetically modified mice in
explaining different pathological conditions that involve MSNs.
PMID- 28503135
TI - The Gut Microbiota and Autism Spectrum Disorders.
AB - Gastrointestinal (GI) symptoms are a common comorbidity in patients with autism
spectrum disorder (ASD), but the underlying mechanisms are unknown. Many studies
have shown alterations in the composition of the fecal flora and metabolic
products of the gut microbiome in patients with ASD. The gut microbiota
influences brain development and behaviors through the neuroendocrine,
neuroimmune and autonomic nervous systems. In addition, an abnormal gut
microbiota is associated with several diseases, such as inflammatory bowel
disease (IBD), ASD and mood disorders. Here, we review the bidirectional
interactions between the central nervous system and the gastrointestinal tract
(brain-gut axis) and the role of the gut microbiota in the central nervous system
(CNS) and ASD. Microbiome-mediated therapies might be a safe and effective
treatment for ASD.
PMID- 28503139
TI - A Pilot Study on the Effects of Transcranial Direct Current Stimulation on Brain
Rhythms and Entropy during Self-Paced Finger Movement using the Epoc Helmet.
AB - Transcranial direct current stimulation (tDCS) of the cerebellum is emerging as a
novel non-invasive tool to modulate the activity of the cerebellar circuitry. In
a single blinded study, we applied anodal tDCS (atDCS) of the cerebellum to
assess its effects on brain entropy and brain rhythms during self-paced
sequential finger movements in a group of healthy volunteers. Although wearable
electroencephalogram (EEG) systems cannot compete with traditional
clinical/laboratory set-ups in terms of accuracy and channel density, they have
now reached a sufficient maturity to envision daily life applications. Therefore,
the EEG was recorded with a comfortable and easy to wear 14 channels wireless
helmet (Epoc headset; electrode location was based on the 10-20 system).
Cerebellar neurostimulation modified brain rhythmicity with a decrease in the
delta band (electrode F3 and T8, p < 0.05). By contrast, our study did not show
any significant change in entropy ratios and laterality coefficients (LC) after
atDCS of the cerebellum in the 14 channels. The cerebellum is heavily connected
with the cerebral cortex including the frontal lobes and parietal lobes via the
cerebello-thalamo-cortical pathway. We propose that the effects of anodal
stimulation of the cerebellar cortex upon cerebral cortical rhythms are mediated
by this key-pathway. Additional studies using high-density EEG recordings and
behavioral correlates are now required to confirm our findings, especially given
the limited coverage of Epoc headset.
PMID- 28503137
TI - Reward Network Immediate Early Gene Expression in Mood Disorders.
AB - Over the past three decades, it has become clear that aberrant function of the
network of interconnected brain regions responsible for reward processing and
motivated behavior underlies a variety of mood disorders, including depression
and anxiety. It is also clear that stress-induced changes in reward network
activity underlying both normal and pathological behavior also cause changes in
gene expression. Here, we attempt to define the reward circuitry and explore the
known and potential contributions of activity-dependent changes in gene
expression within this circuitry to stress-induced changes in behavior related to
mood disorders, and contrast some of these effects with those induced by exposure
to drugs of abuse. We focus on a series of immediate early genes regulated by
stress within this circuitry and their connections, both well-explored and
relatively novel, to circuit function and subsequent reward-related behaviors. We
conclude that IEGs play a crucial role in stress-dependent remodeling of reward
circuitry, and that they may serve as inroads to the molecular, cellular, and
circuit-level mechanisms of mood disorder etiology and treatment.
PMID- 28503141
TI - Addiction as an Attachment Disorder: White Matter Impairment Is Linked to
Increased Negative Affective States in Poly-Drug Use.
AB - Substance use disorders (SUD) have been shown to be linked to various neuronal
and behavioral impairments. In this study, we investigate whether there is a
connection between the integrity of white matter (WM) and attachment styles as
well as different affective states including spirituality in a group of patients
diagnosed for poly-drug use disorder (PUD) in comparison to non-clinical
controls. A total sample of 59 right-handed men, comprising the groups of
patients with PUD (n = 19), recreational drug-using individuals (RUC; n = 20) as
well as non-drug using controls were recruited (NUC; n = 20). For the behavioral
assessment, we applied the Adult Attachment-Scale, the Affective Neuroscience
Personality-Scale (short version) and the Multidimensional Inventory for
Religious/Spiritual Well-Being. Diffusion Tensor Imaging was used to investigate
differences in WM neural connectivity. Analyses revealed decreased Fractional
Anisotropy and decreased Mean Diffusivity in PUD patients as compared to RUC and
NUC. No differences were found between RUC and NUC. Additional ROI analyses
suggested that WM impairment in the superior longitudinal fasciculus (SLF) and
the superior corona radiata (SCR) was linked to more insecure attachment as well
as to more negative affectivity. No substantial correlation was observed with
spirituality. These findings are mainly limited by the cross-sectional design of
the study. However, our preliminary results support the idea of addiction as an
attachment disorder, both at neuronal and behavioral levels. Further research
might be focused on the changes of insecure attachment patterns in SUD treatment
and their correlation with changes in the brain.
PMID- 28503138
TI - Enhanced Feedback-Related Negativity in Alzheimer's Disease.
AB - Alzheimer's disease (AD), the most common cause of dementia in the elderly,
results in the impairment of executive function, including that of performance
monitoring. Feedback-related negativity (FRN) is an electrophysiological measure
reflecting the activity of this monitoring system via feedback signals, and is
generated from the anterior cingulate cortex. However, there have been no reports
on FRN in AD. Based on prior aging studies, we hypothesized that FRN would
decrease in AD patients. To assess this, FRN was measured in healthy individuals
and those with AD during a simple gambling task involving positive and negative
feedback stimuli. Contrary to our hypothesis, FRN amplitude increased in AD
patients, compared with the healthy elderly. We speculate that this may reflect
the existence of a compensatory mechanism against the decline in executive
function. Also, there was a significant association between FRN amplitude and
depression scores in AD, and the FRN amplitude tended to increase insomuch as the
Self-rating Depression Scale (SDS) was higher. This result suggests the existence
of a negative bias in the affective state in AD. Thus, the impaired functioning
monitoring system in AD is a more complex phenomenon than we thought.
PMID- 28503142
TI - Brain Gray Matter Atrophy after Spinal Cord Injury: A Voxel-Based Morphometry
Study.
AB - The aim of this study was to explore possible changes in whole brain gray matter
volume (GMV) after spinal cord injury (SCI) using voxel-based morphometry (VBM),
and to study their associations with the injury duration, severity, and clinical
variables. In total, 21 patients with SCI (10 with complete and 11 with
incomplete SCI) and 21 age- and sex-matched healthy controls (HCs) were
recruited. The 3D high-resolution T1-weighted structural images of all subjects
were obtained using a 3.0 Tesla MRI system. Disease duration and American Spinal
Injury Association (ASIA) Scale scores were also obtained from each patient.
Voxel-based morphometry analysis was carried out to investigate the differences
in GMV between patients with SCI and HCs, and between the SCI sub-groups.
Associations between GMV and clinical variables were also analyzed. Compared with
HCs, patients with SCI showed significant GMV decrease in the dorsal anterior
cingulate cortex, bilateral anterior insular cortex, bilateral orbital frontal
cortex (OFC), and right superior temporal gyrus. No significant difference in GMV
in these areas was found either between the complete and incomplete SCI sub
groups, or between the sub-acute (duration <1 year) and chronic (duration >1
year) sub-groups. Finally, the GMV of the right OFC was correlated with the
clinical motor scores of left extremities in not only all SCI patients, but
especially the CSCI subgroup. In the sub-acute subgroup, we found a significant
positive correlation between the dACC GMV and the total clinical motor scores,
and a significant negative correlation between right OFC GMV and the injury
duration. These findings indicate that SCI can cause remote atrophy of brain gray
matter, especially in the salient network. In general, the duration and severity
of SCI may be not associated with the degree of brain atrophy in total SCI
patients, but there may be associations between them in subgroups.
PMID- 28503140
TI - Gravity as a Strong Prior: Implications for Perception and Action.
AB - In the future, humans are likely to be exposed to environments with altered
gravity conditions, be it only visually (Virtual and Augmented Reality), or
visually and bodily (space travel). As visually and bodily perceived gravity as
well as an interiorized representation of earth gravity are involved in a series
of tasks, such as catching, grasping, body orientation estimation and spatial
inferences, humans will need to adapt to these new gravity conditions.
Performance under earth gravity discrepant conditions has been shown to be
relatively poor, and few studies conducted in gravity adaptation are rather
discouraging. Especially in VR on earth, conflicts between bodily and visual
gravity cues seem to make a full adaptation to visually perceived earth
discrepant gravities nearly impossible, and even in space, when visual and bodily
cues are congruent, adaptation is extremely slow. We invoke a Bayesian framework
for gravity related perceptual processes, in which earth gravity holds the status
of a so called "strong prior". As other strong priors, the gravity prior has
developed through years and years of experience in an earth gravity environment.
For this reason, the reliability of this representation is extremely high and
overrules any sensory information to its contrary. While also other factors such
as the multisensory nature of gravity perception need to be taken into account,
we present the strong prior account as a unifying explanation for empirical
results in gravity perception and adaptation to earth-discrepant gravities.
PMID- 28503143
TI - Impairments of Motor Function While Multitasking in HIV.
AB - Human immunodeficiency virus (HIV) became a treatable illness with the
introduction of combination antiretroviral therapy (CART). As a result, patients
with regular access to CART are expected to live decades with HIV. Long-term HIV
infection presents unique challenges, including neurocognitive impairments
defined by three major stages of HIV-associated neurocognitive disorders (HAND).
The current investigation aimed to study cognitive and motor impairments in HIV
using a novel multitasking paradigm. Unlike current standard measures of
cognitive and motor performance in HIV, multitasking increases real-world
validity by mimicking the dual motor and cognitive demands that are part of daily
professional and personal settings (e.g., driving, typing and writing). Moreover,
multitask assessments can unmask compensatory mechanisms, normally used under
single task conditions, to maintain performance. This investigation revealed that
HIV+ participants were impaired on the motor component of the multitask, while
cognitive performance was spared. A patient-specific positive interaction between
motor performance and working memory recall was driven by poor HIV+ multitaskers.
Surprisingly, HAND stage did not correspond with multitask performance and a
variety of commonly used assessments indicated normal motor function among HIV+
participants with poor motor performance during the experimental task. These
results support the use of multitasks to reveal otherwise hidden impairment in
chronic HIV by expanding the sensitivity of clinical assessments used to
determine HAND stage. Future studies should examine the capability of multitasks
to predict performance in personal, professional and health-related behaviors and
prognosis of patients living with chronic HIV.
PMID- 28503145
TI - A Neural-Dynamic Architecture for Concurrent Estimation of Object Pose and
Identity.
AB - Handling objects or interacting with a human user about objects on a shared
tabletop requires that objects be identified after learning from a small number
of views and that object pose be estimated. We present a neurally inspired
architecture that learns object instances by storing features extracted from a
single view of each object. Input features are color and edge histograms from a
localized area that is updated during processing. The system finds the best
matching view for the object in a novel input image while concurrently estimating
the object's pose, aligning the learned view with current input. The system is
based on neural dynamics, computationally operating in real time, and can handle
dynamic scenes directly off live video input. In a scenario with 30 everyday
objects, the system achieves recognition rates of 87.2% from a single training
view for each object, while also estimating pose quite precisely. We further
demonstrate that the system can track moving objects, and that it can segment the
visual array, selecting and recognizing one object while suppressing input from
another known object in the immediate vicinity. Evaluation on the COIL-100
dataset, in which objects are depicted from different viewing angles, revealed
recognition rates of 91.1% on the first 30 objects, each learned from four
training views.
PMID- 28503144
TI - Rigid Ankle Foot Orthosis Deteriorates Mediolateral Balance Control and Vertical
Braking during Gait Initiation.
AB - Rigid ankle-foot orthoses (AFO) are commonly used for impeding foot drop during
the swing phase of gait. They also reduce pain and improve gait kinematics in
patients with weakness or loss of integrity of ankle-foot complex structures due
to various pathological conditions. However, this comes at the price of
constraining ankle joint mobility, which might affect propulsive force generation
and balance control. The present study examined the effects of wearing an AFO on
biomechanical variables and electromyographic activity of tibialis anterior (TA)
and soleus muscles during gait initiation (GI). Nineteen healthy adults
participated in the study. They initiated gait at a self-paced speed with no
ankle constraint as well as wearing an AFO on the stance leg, or bilaterally.
Constraining the stance leg ankle decreased TA activity ipsilaterally during the
anticipatory postural adjustment (APA) of GI, and ipsilateral soleus activity
during step execution. In the sagittal plane, the decrease in the stance leg TA
activity reduced the backward displacement of the center of pressure (CoP)
resulting in a reduction of the forward velocity of the center of mass (CoM)
measured at foot contact (FC). In the frontal plane, wearing the AFO reduced the
displacement of the CoP in the direction of the swing leg during the APA phase.
The mediolateral velocity of the CoM increased during single-stance prompting a
larger step width to recover balance. During step execution, the CoM vertical
downward velocity is normally reduced in order to lessen the impact of the swing
leg with the floor and facilitates the rise of the CoM that occurs during the
subsequent double-support phase. The reduction in stance leg soleus activity
caused by constraining the ankle weakened the vertical braking of the CoM during
step execution. This caused the absolute instantaneous vertical velocity of the
CoM at FC to be greater in the constrained conditions with respect to the control
condition. From a rehabilitation perspective, passively- or actively-powered
assistive AFOs could correct for the reduction in muscle activity and enhance
balance control during GI of patients.
PMID- 28503146
TI - Statin Therapy Is Associated with Reduced Risk of Peptic Ulcer Disease in the
Taiwanese Population.
AB - Although statin use may affect the severity of chronic gastritis and gastric
cancer, no data exists about the relationship between statin therapy and risk of
peptic ulcer disease (PUD) in patients. We investigated the effect of statin use
and the incidence of PUD from the Taiwan National Health Insurance Research
Database (NHIRD). A total of 35,194 patients records for medical claims were
enrolled. We performed a population-based case-control analysis to compare the
incidence of PUD in patients who were prescribed statins and that in patients who
were not. In the univariate logistic analysis, we found that statin was not
significant risk of PUD. However, a multivariate model indicates that satin use
was significantly associated with a reduced risk of PUD (adjusted odds ratio
[aOR] = 0.87, 95% CI = 0.82-0.93, P < 0.001). The cumulative defined daily dose
(DDD) was analyzed. Patients who prescribed fluvastatin >=280 DDD, atorvastatin
>=200 DDD, and pravastatin >=130 DDD dramatically decreased risk for PUD (aOR =
0.58, 0.67, and 0.71; 95% CI = 0.46-0.74, 0.57-0.78, and 0.56-0.91,
respectively). Our results showed that statin therapy reduced the risk of PUD and
this was associated with the high cumulative DDD of prescribed statins. This
study reveals that active use of statins to be associated with decreased risk for
PUD.
PMID- 28503147
TI - An Ethanolic Extract of Ampelopsis Radix Exerts Anti-colorectal Cancer Effects
and Potently Inhibits STAT3 Signaling In Vitro.
AB - Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and
mortality worldwide. Signal transducer and activator of transcription 3 (STAT3)
signaling is constantly activated in CRC, and has been proposed as a pathogenic
factor and a therapeutic target of CRC. Ampelopsis Radix (AR), a traditional
Chinese medicinal herb, possesses low toxicity and has long been used clinically
for the treatment of cancers including CRC. Some constituents of AR have been
reported to exert anti-cancer properties by targeting STAT3. However, the anti
CRC mode and mechanism of action of AR have not been fully elucidated. Here, we
investigated the involvement of STAT3 signaling in the anti-CRC effects of AR.
Results showed that AR reduced cell viability, induced cell apoptosis, and
suppressed cell migration and invasion in human HCT-116 and SW480 CRC cells.
Mechanistic studies showed that AR potently suppressed STAT3 and Src
phosphorylation, and inhibited STAT3 nuclear localization in cultured CRC cells.
AR also downregulated the expression of STAT3 target genes Mcl-1, Bcl-xL, and MMP
2 that are involved in cell survival and mobility. Moreover, the cytotoxic effect
of AR was diminished by overexpressing STAT3C, a persistent active variant of
STAT3. In conclusion, AR exerted anti-CRC effects in vitro and these effects are
at least in part attributed to the inhibition of STAT3 signaling. Our findings
provide a molecular justification for the traditional use of AR in treating CRC,
and a pharmacological basis for developing AR-derived modern anti-CRC agent(s).
PMID- 28503148
TI - Management of Benign Prostatic Hyperplasia: Could Dietary Polyphenols Be an
Alternative to Existing Therapies?
AB - The incidence of benign prostatic hyperplasia (BPH) is gradually on the increase.
While conventional drugs such as the alpha1-adrenergic receptor antagonists and
5alpha-reductase inhibitors have been found to be useful in the treatment of BPH,
the adverse side effects associated with their usage, have led to increased
search for alternative means of managing this disease. Furthermore, although
surgery has also been suggested to be a sure method, the cost and risks
associated with it excludes it as a routine treatment. Dietary polyphenols have
gained public interest in recent times due to their roles in the prevention of
various diseases that implicate free radicals/reactive oxygen species. However,
their roles in the management of BPH have not been explored. Hence, this review
on their prospects in the management of BPH and their mechanisms of action.
Literature search was carried out in several electronic data bases such as
PubMed, Google Scholar, Medline, Agora, and Hinari from1970 to 2017 to identify
the current status of knowledge on this concept. The findings from these data
bases suggest that while dietary polyphenols may not replace the need for the
existing therapies in the management of BPH, they hold promise in BPH management
which could be explored by researchers working in this field.
PMID- 28503149
TI - Vascular Kinin B1 and B2 Receptors Determine Endothelial Dysfunction through
Neuronal Nitric Oxide Synthase.
AB - B1- and B2-kinin receptors are G protein-coupled receptors that play an important
role in the vascular function. Therefore, the present study was designed to
evaluate the participation of kinin receptors in the acetylcholine (ACh)-induced
vascular relaxation, focusing on the protein-protein interaction involving kinin
receptors with endothelial and neuronal nitric oxide synthases (eNOS and nNOS).
Vascular reactivity, nitric oxide (NO.) and reactive oxygen species (ROS)
generation, co-immunoprecipitation were assessed in thoracic aorta from male wild
type (WT), B1- (B1R-/-), B2- (B2R-/-) knockout mice. Some vascular reactivity
experiments were also performed in a double kinin receptors knockout mice (B1B2R
/-). For pharmacological studies, selective B1- and B2-kinin receptors
antagonists, NOS inhibitors and superoxide dismutase (SOD) mimetic were used.
First, we show that B1- and B2-kinin receptors form heteromers with nNOS and eNOS
in thoracic aorta. To investigate the functionality of these protein-protein
interactions, we took advantage of pharmacological tools and knockout mice.
Importantly, our results show that kinin receptors regulate ACh-induced
relaxation via nNOS signaling in thoracic aorta with no changes in NO. donor
induced relaxation. Interestingly, B1B2R-/- presented similar level of vascular
dysfunction as found in B1R-/- or B2R-/- mice. In accordance, aortic rings from
B1R-/- or B2R-/- mice exhibit decreased NO. bioavailability and increased
superoxide generation compared to WT mice, suggesting the involvement of
excessive ROS generation in the endothelial dysfunction of B1R-/- and B2R-/-
mice. Alongside, we show that impaired endothelial vasorelaxation induced by ACh
in B1R-/- or B2R-/- mice was rescued by the SOD mimetic compound. Taken together,
our findings show that B1- and B2-kinin receptors regulate the endothelium
dependent vasodilation of ACh through nNOS activity and indicate that molecular
disturbance of short-range interaction between B1- and B2-kinin receptors with
nNOS might be involved in the oxidative pathogenesis of endothelial dysfunction.
PMID- 28503150
TI - Dental Pulp Cells Isolated from Teeth with Superficial Caries Retain an
Inflammatory Phenotype and Display an Enhanced Matrix Mineralization Potential.
AB - We have isolated dental pulp cells (DPCs) from three healthy (hDPCs) and three
carious (cDPCs) donors and shown that compared to hDPCs cells isolated from
superficial carious lesions show higher clonogenic potential; show an equivalent
proportion of cells with putative stem cell surface markers; show enhanced matrix
mineralization capability; have enhanced angiogenic marker expression and retain
the inflammatory phenotype in vitro characteristic of superficial caries lesions
in vivo. Our findings suggest that cDPCs may be used for further investigation of
the cross talk between inflammatory, angiogenic and mineralization pathways in
repair of carious pulp. In addition cells derived from carious pulps (almost
always discarded) may have potential for future applications in mineralized
tissue repair and regeneration.
PMID- 28503151
TI - Identification of a Novel UT-B Urea Transporter in Human Urothelial Cancer.
AB - The urea transporter UT-B is widely expressed and has been studied in
erythrocyte, kidney, brain and intestines. Interestingly, UT-B gene has been
found more abundant in bladder than any other tissue. Recently, gene analyses
demonstrate that SLC14A1 (UT-B) gene mutations are associated with bladder
cancer, suggesting that urea transporter UT-B may play an important role in
bladder carcinogenesis. In this study, we examined UT-B expression in bladder
cancer with human primary bladder cancer tissues and cancer derived cell lines.
Human UT-B has two isoforms. We found that normal bladder expresses long form of
UT-B2 but was lost in 8 of 24 (33%) or significantly downregulated in 16 of 24
(67%) of primary bladder cancer patients. In contrast, the short form of UT-B1
lacking exon 3 was detected in 20 bladder cancer samples. Surprisingly, a 24-nt
in-frame deletion in exon 4 in UT-B1 (UT-B1Delta24) was identified in 11 of 20
(55%) bladder tumors. This deletion caused a functional defect of UT-B1.
Immunohistochemistry revealed that UT-B protein levels were significantly
decreased in bladder cancers. Western blot analysis showed a weak UT-B band of 40
kDa in some tumors, consistent with UT-B1 gene expression detected by RT-PCR.
Interestingly, bladder cancer associate UT-B1Delta24 was barely sialylated,
reflecting impaired glycosylation of UT-B1 in bladder tumors. In conclusion,
SLC14A1 gene and UT-B protein expression are significantly changed in bladder
cancers. The aberrant UT-B expression may promote bladder cancer development or
facilitate carcinogenesis induced by other carcinogens.
PMID- 28503152
TI - Identification, Classification, and Expression Analysis of GRAS Gene Family in
Malus domestica.
AB - GRAS genes encode plant-specific transcription factors that play important roles
in plant growth and development. However, little is known about the GRAS gene
family in apple. In this study, 127 GRAS genes were identified in the apple
(Malus domestica Borkh.) genome and named MdGRAS1 to MdGRAS127 according to their
chromosomal locations. The chemical characteristics, gene structures and
evolutionary relationships of the MdGRAS genes were investigated. The 127 MdGRAS
genes could be grouped into eight subfamilies based on their structural features
and phylogenetic relationships. Further analysis of gene structures, segmental
and tandem duplication, gene phylogeny and tissue-specific expression with
ArrayExpress database indicated their diversification in quantity, structure and
function. We further examined the expression pattern of MdGRAS genes during apple
flower induction with transcriptome sequencing. Eight higher MdGRAS (MdGRAS6, 26,
28, 44, 53, 64, 107, and 122) genes were surfaced. Further quantitative reverse
transcription PCR indicated that the candidate eight genes showed distinct
expression patterns among different tissues (leaves, stems, flowers, buds, and
fruits). The transcription levels of eight genes were also investigated with
various flowering related treatments (GA3, 6-BA, and sucrose) and different
flowering varieties (Yanfu No. 6 and Nagafu No. 2). They all were affected by
flowering-related circumstance and showed different expression level. Changes in
response to these hormone or sugar related treatments indicated their potential
involvement during apple flower induction. Taken together, our results provide
rich resources for studying GRAS genes and their potential clues in genetic
improvement of apple flowering, which enriches biological theories of GRAS genes
in apple and their involvement in flower induction of fruit trees.
PMID- 28503153
TI - Investigating Engineered Ribonucleoprotein Particles to Improve Oral RNAi
Delivery in Crop Insect Pests.
AB - Genetically modified (GM) crops producing double-stranded RNAs (dsRNAs) are being
investigated largely as an RNA interference (RNAi)-based resistance strategy
against crop insect pests. However, limitations of this strategy include the
sensitivity of dsRNA to insect gut nucleases and its poor insect cell membrane
penetration. Working with the insect pest cotton boll weevil (Anthonomus
grandis), we showed that the chimeric protein PTD-DRBD (peptide transduction
domain-dsRNA binding domain) combined with dsRNA forms a ribonucleoprotein
particle (RNP) that improves the effectiveness of the RNAi mechanism in the
insect. The RNP slows down nuclease activity, probably by masking the dsRNA.
Furthermore, PTD-mediated internalization in insect gut cells is achieved within
minutes after plasma membrane contact, limiting the exposure time of the RNPs to
gut nucleases. Therefore, the RNP provides an approximately 2-fold increase in
the efficiency of insect gene silencing upon oral delivery when compared to naked
dsRNA. Taken together, these data demonstrate the role of engineered RNPs in
improving dsRNA stability and cellular entry, representing a path toward the
design of enhanced RNAi strategies in GM plants against crop insect pests.
PMID- 28503154
TI - Sedentary Patterns, Physical Activity, and Cardiorespiratory Fitness in
Association to Glycemic Control in Type 2 Diabetes Patients.
AB - Background: Sedentary behavior has been considered an independent risk factor for
type-2 diabetes (T2D), with a negative impact on several physiological outcomes,
whereas breaks in sedentary time (BST) have been proposed as a viable solution to
mitigate some of these effects. However, little is known about the independent
associations of sedentary pursuits, physical activity, and cardiorespiratory
fitness (CRF) variables with glycemic control. We investigated the independent
associations of total sedentary time, BST, moderate-to-vigorous physical activity
(MVPA), and CRF with glycemic outcomes in patients with T2D. Methods: Total
sedentary time, BST, and MVPA were assessed in 66 participants (29 women) with
T2D, using accelerometry. Glucose and insulin were measured during a mixed meal
tolerance test, with the respective calculations of HOMA-IR and Matsuda index.
Glycated hemoglobin (HbA1c) was also analyzed. CRF was measured in a maximal
treadmill test with breath-by-breath gases analysis. Multiple regressions were
used for data analysis. Results: Regardless of CRF, total sedentary time was
positively associated with HbA1c (beta = 0.25, p = 0.044). Adjusting for MVPA,
total sedentary time was related to fasting glucose (beta = 0.32, p = 0.037). No
associations between total sedentary time and the remaining glycemic outcomes,
after adjusting for MVPA. BST had favorable associations with HOMA-IR (beta =
0.28, p = 0.047) and fasting glucose (beta = -0.25, p = 0.046), when adjusted for
MVPA, and with HOMA-IR (beta = -0.25, p = 0.036), Matsuda index (beta = 0.26, p =
0.036), and fasting glucose (beta = -0.22, p = 0.038), following adjustment for
CRF. When adjusting for total sedentary time, only CRF yielded favorable
associations with HOMA-IR (beta = -0.29, p = 0.039), fasting glucose (beta =
0.32, p = 0.012), and glucose at 120-min (beta = -0.26, p = 0.035), and no
associations were found for MVPA with none of the metabolic outcomes. Conclusion:
The results from this study suggest that sedentary time and patterns are relevant
for the glycemic control in patients with T2D. Still, MVPA and CRF counteracted
most of the associations for total sedentary time but not for the BST. MVPA was
not associated with metabolic outcomes, and CRF lost some of the associations
with glycemic indicators when adjusted for total sedentary time. Future
interventions aiming to control/improve T2D must consider reducing and breaking
up sedentary time as a viable strategy to improve glycemic control.
PMID- 28503155
TI - DJINNI: A Novel Technology Supported Exposure Therapy Paradigm for SAD Combining
Virtual Reality and Augmented Reality.
AB - The present paper explores the benefits and the capabilities of various emerging
state-of-the-art interactive 3D and Internet of Things technologies and
investigates how these technologies can be exploited to develop a more effective
technology supported exposure therapy solution for social anxiety disorder.
"DJINNI" is a conceptual design of an in vivo augmented reality (AR) exposure
therapy mobile support system that exploits several capturing technologies and
integrates the patient's state and situation by vision-based, audio-based, and
physiology-based analysis as well as by indoor/outdoor localization techniques.
DJINNI also comprises an innovative virtual reality exposure therapy system that
is adaptive and customizable to the demands of the in vivo experience and
therapeutic progress. DJINNI follows a gamification approach where rewards and
achievements are utilized to motivate the patient to progress in her/his
treatment. The current paper reviews the state of the art of technologies needed
for such a solution and recommends how these technologies could be integrated in
the development of an individually tailored and yet feasible and effective
AR/virtual reality-based exposure therapy. Finally, the paper outlines how DJINNI
could be part of classical cognitive behavioral treatment and how to validate
such a setup.
PMID- 28503157
TI - A Review of Self-regulated Learning: Six Models and Four Directions for Research.
AB - Self-regulated learning (SRL) includes the cognitive, metacognitive, behavioral,
motivational, and emotional/affective aspects of learning. It is, therefore, an
extraordinary umbrella under which a considerable number of variables that
influence learning (e.g., self-efficacy, volition, cognitive strategies) are
studied within a comprehensive and holistic approach. For that reason, SRL has
become one of the most important areas of research within educational psychology.
In this paper, six models of SRL are analyzed and compared; that is, Zimmerman;
Boekaerts; Winne and Hadwin; Pintrich; Efklides; and Hadwin, Jarvela and Miller.
First, each model is explored in detail in the following aspects: (a) history and
development, (b) description of the model (including the model figures), (c)
empirical support, and (d) instruments constructed based on the model. Then, the
models are compared in a number of aspects: (a) citations, (b) phases and
subprocesses, (c) how they conceptualize (meta)cognition, motivation and emotion,
(d) top-down/bottom-up, (e) automaticity, and (f) context. In the discussion, the
empirical evidence from the existing SRL meta-analyses is examined and
implications for education are extracted. Further, four future lines of research
are proposed. The review reaches two main conclusions. First, the SRL models form
an integrative and coherent framework from which to conduct research and on which
students can be taught to be more strategic and successful. Second, based on the
available meta-analytic evidence, there are differential effects of SRL models in
light of differences in students' developmental stages or educational levels.
Thus, scholars and teachers need to start applying these differential effects of
the SRL models and theories to enhance students' learning and SRL skills.
PMID- 28503158
TI - Image Feature Types and Their Predictions of Aesthetic Preference and
Naturalness.
AB - Previous research has investigated ways to quantify visual information of a scene
in terms of a visual processing hierarchy, i.e., making sense of visual
environment by segmentation and integration of elementary sensory input. Guided
by this research, studies have developed categories for low-level visual features
(e.g., edges, colors), high-level visual features (scene-level entities that
convey semantic information such as objects), and how models of those features
predict aesthetic preference and naturalness. For example, in Kardan et al.
(2015a), 52 participants provided aesthetic preference and naturalness ratings,
which are used in the current study, for 307 images of mixed natural and urban
content. Kardan et al. (2015a) then developed a model using low-level features to
predict aesthetic preference and naturalness and could do so with high accuracy.
What has yet to be explored is the ability of higher-level visual features (e.g.,
horizon line position relative to viewer, geometry of building distribution
relative to visual access) to predict aesthetic preference and naturalness of
scenes, and whether higher-level features mediate some of the association between
the low-level features and aesthetic preference or naturalness. In this study we
investigated these relationships and found that low- and high- level features
explain 68.4% of the variance in aesthetic preference ratings and 88.7% of the
variance in naturalness ratings. Additionally, several high-level features
mediated the relationship between the low-level visual features and aaesthetic
preference. In a multiple mediation analysis, the high-level feature mediators
accounted for over 50% of the variance in predicting aesthetic preference. These
results show that high-level visual features play a prominent role predicting
aesthetic preference, but do not completely eliminate the predictive power of the
low-level visual features. These strong predictors provide powerful insights for
future research relating to landscape and urban design with the aim of maximizing
subjective well-being, which could lead to improved health outcomes on a larger
scale.
PMID- 28503156
TI - Effects of Antipsychotic Administration on Brain Glutamate in Schizophrenia: A
Systematic Review of Longitudinal 1H-MRS Studies.
AB - Schizophrenia is associated with brain glutamate dysfunction, but it is currently
unclear whether antipsychotic administration can reduce the extent of
glutamatergic abnormality. We conducted a systematic review of proton magnetic
resonance spectroscopy (1H-MRS) studies examining the effects of antipsychotic
treatment on brain glutamate levels in schizophrenia. The Medline database was
searched to identify relevant articles published until December 2016. Inclusion
required that studies examined longitudinal changes in brain glutamate
metabolites in patients with schizophrenia before and after initiation of first
antipsychotic treatment or a switch in antipsychotic treatment. The searches
identified eight eligible articles, with baseline and follow-up measures in a
total of 168 patients. The majority of articles reported a numerical reduction in
brain glutamate metabolites with antipsychotic treatment, and the estimated
overall mean reduction of 6.5% in Glx (the combined signal from glutamate and
glutamine) across brain regions. Significant reductions in glutamate metabolites
in at least one brain region were reported in four of the eight studies, and none
of the studies reported a significant glutamatergic increase after antipsychotic
administration. Relationships between the degree of change in glutamate and the
degree of improvement in symptoms have been inconsistent but may provide limited
evidence that antipsychotic response may be associated with lower glutamate
levels before treatment and a greater extent of glutamatergic reduction during
treatment. Further longitudinal, prospective studies of glutamate and
antipsychotic response are required to confirm these findings.
PMID- 28503159
TI - Quantifying the Degree of Movement Dissimilarity between Two Distinct Action
Scenarios: An Exploratory Approach with Procrustes Analysis.
AB - Game consoles allow subjects to perform movements which are visually similar to
the movements performed in 'real' world scenarios. Beyond entertainment, virtual
reality devices are being used in several domains: sports performance; motor
rehabilitation; training of risk professions. This article presents the
Procrustes method to measure the degree of dissimilarity between movements
performed in 'real' and 'virtual' scenarios. For this purpose, the 501 darts game
and a video darts game played on a console were used. The participants' arm
throwing movements were video recorded and digitized. The matrices of x and y
coordinates of the movements of the wrist, elbow, and shoulder in both
performance scenarios were subjected to the Procrustes method. The wrist displays
the most extreme dissimilarity values (higher than elbow and shoulder). Results
also revealed smaller dissimilarity values for movements performed under the same
conditions (e.g., real-real) and larger dissimilarity values between movements
performed in different scenarios.
PMID- 28503160
TI - Challenging Cognitive Control by Mirrored Stimuli in Working Memory Matching.
AB - Cognitive conflict has often been investigated by placing automatic processing
originating from learned associations in competition with instructed task
demands. Here we explore whether mirror generalization as a congenital mechanism
can be employed to create cognitive conflict. Past research suggests that the
visual system automatically generates an invariant representation of visual
objects and their mirrored counterparts (i.e., mirror generalization), and
especially so for lateral reversals (e.g., a cup seen from the left side vs.
right side). Prior work suggests that mirror generalization can be reduced or
even overcome by learning (i.e., for those visual objects for which it is not
appropriate, such as letters d and b). We, therefore, minimized prior practice on
resolving conflicts involving mirror generalization by using kanji stimuli as non
verbal and unfamiliar material. In a 1-back task, participants had to check a
stream of kanji stimuli for identical repetitions and avoid miss-categorizing
mirror reversed stimuli as exact repetitions. Consistent with previous work,
lateral reversals led to profound slowing of reaction times and lower accuracy in
Experiment 1. Yet, different from previous reports suggesting that lateral
reversals lead to stronger conflict, similar slowing for vertical and horizontal
mirror transformations was observed in Experiment 2. Taken together, the results
suggest that transformations of visual stimuli can be employed to challenge
cognitive control in the 1-back task.
PMID- 28503161
TI - Exploring Task-Specific Independent Standing in 3- to 5-Month-Old Infants.
AB - Perspectives on developmental milestones suggest that an infant's ability to
stand without support occurs at the age of 9-16 months. The two exploratory tasks
were part of a baby swimming routine, conducted over a period of 12 weeks (24
sessions), and the aim was to examine whether young infants (mean age 97 days)
improved their performance in standing as measured by prolonged time-to-stand.
The data suggest that 3- to 5-month-old infants are capable of demonstrating
signs of motor learning in task-specific standing. The results appear remarkable
when compared to the expected age required for other forms of independent
standing. The developmental process of independent standing is discussed in
relation to the complex interaction between genetic and environmental factors.
PMID- 28503162
TI - New Evaluation of the Electronically Activated Recorder (EAR): Obtrusiveness,
Compliance, and Participant Self-selection Effects.
AB - The Electronically Activated Recorder (EAR) is a method for collecting periodic
brief audio snippets of participants' daily lives using a portable recording
device. The EAR can potentially intrude into people's privacy, alter their
natural behavior, and introduce self-selection biases greater than in other types
of social science methods. Previous research (Mehl and Holleran, 2007, hereafter
M&H) has shown that participant non-compliance with, and perceived obtrusiveness
of, an EAR protocol are both low. However, these questions have not been
addressed in jurisdictions that require the consent of all parties to recording
conversations. This EAR study required participants to wear a button bearing a
microphone icon and the words "This conversation may be recorded" to comply with
California's all-party consent law. Results revealed self-reported obtrusiveness
and non-compliance were actually lower in the present study than in the M&H
study. Behaviorally assessed non-compliance did not differ between the two
studies. Participants in the present study talked more about being in the study
than participants in the M&H study, but such talk still comprised <2% of sampled
conversations. Another potential problem with the EAR, participant self-selection
bias, was addressed by comparing the EAR volunteers' HEXACO personality
dimensions to a non-volunteer sample drawn from the same student population. EAR
volunteers were significantly and moderately higher in Conscientiousness, and
lower in Emotionality, than non-volunteers. In conclusion, the EAR method can be
successfully implemented in at least one all-party consent state (California).
Interested researchers are encouraged to review this procedure with their own
legal counsel.
PMID- 28503163
TI - Different Effects of Cold Stimulation on Reflex and Non-Reflex Components of
Poststroke Spastic Hypertonia.
AB - OBJECTIVE: To use an established biomechanical approach to quantify reflex and
non-reflex responses from spastic-paretic elbow flexors in response to controlled
cold and heat stimulation. METHODS: Thirteen spastic-hemiplegic stroke subjects
were tested in the experiment. The spastic elbow joint was stretched into
extension for 50 degrees at two speeds (5 degrees /s and 100 degrees /s) in a
customized apparatus. Thermal stimulation (HEAT at heat pain threshold, COLD at 0
degrees C, or BASELINE at room temperature) was applied to the thenar eminence of
the contralateral hand immediately prior to stretching for at least 30 s.
RESULTS: Total torque was greater at 100 degrees /s than at 5 degrees /s. Total
torque was significantly increased after COLD, but not HEAT as compared to
BASELINE. When normalized to total torque at baseline, HEAT decreased total
torque by 6.3%, while COLD increased total torque by 11.0%. There was no
significant difference in the reflex torque among three thermal conditions.
CONCLUSION: The findings demonstrate differentiated effects of cold stimulation
on the total resistance from spastic muscles. They provide objective evidence for
anecdotal clinical observations of increased muscle spasticity by cold exposure.
PMID- 28503164
TI - Superior Canal Dehiscence Syndrome: Lessons from the First 20 Years.
AB - Superior semicircular canal dehiscence syndrome was first reported by Lloyd Minor
and colleagues in 1998. Patients with a dehiscence in the bone overlying the
superior semicircular canal experience symptoms of pressure or sound-induced
vertigo, bone conduction hyperacusis, and pulsatile tinnitus. The initial series
of patients were diagnosed based on common symptoms, a physical examination
finding of eye movements in the plane of the superior semicircular canal when ear
canal pressure or loud tones were applied to the ear, and high-resolution
computed tomography imaging demonstrating a dehiscence in the bone over the
superior semicircular canal. Research productivity directed at understanding
better methods for diagnosing and treating this condition has substantially
increased over the last two decades. We now have a sound understanding of the
pathophysiology of third mobile window syndromes, higher resolution imaging
protocols, and several sensitive and specific diagnostic tests. Furthermore, we
have a treatment (surgical occlusion of the superior semicircular canal) that has
demonstrated efficacy. This review will highlight some of the fundamental
insights gained in SCDS, propose diagnostic criteria, and discuss future research
directions.
PMID- 28503166
TI - Inhibition of Ectopic Arginine Vasopressin Production by Phenytoin in the Small
Cell Lung Cancer Cell Line Lu-165.
AB - Phenytoin, a voltage-gated sodium channel (NaV channel) antagonist, reportedly
inhibits arginine vasopressin (AVP) release from an isolated rat neurohypophysis.
So far, it is uncertain whether phenytoin has a direct action on ectopic AVP
producing neuroendocrine tumors. We studied the effect of phenytoin on the
release of copeptin, the C-terminal fragment of pro-AVP, and expression of AVP
gene in the human small cell lung cancer cell line Lu-165. Cells were maintained
in RPMI1640 medium with 10% fetal bovine serum and were used within the fifth
passage. Copeptin was detected using a new sandwich immunoassay, and AVP mRNA
levels were measured using real-time reverse transcription polymerase chain
reaction. Treatment with phenytoin at a concentration of 25 ug/mL, but not at 5
or 10 ug/mL, had an inhibitory effect on copeptin levels in the medium at 48 h.
At the same concentration, AVP mRNA levels in Lu-165 cells also decreased.
Although a sodium challenge with added sodium at 20 mEq/L increased copeptin
levels in the medium, a sodium challenge with added sodium at 10 and 20 mEq/L had
no effect on AVP mRNA levels. Phenytoin at a concentration of 25 ug/mL suppressed
copeptin levels in the medium under the sodium challenge with added sodium at 10
and 20 mEq/L. Phenytoin at a concentration of 25 ug/mL also decreased AVP mRNA
levels in Lu-165 cells under the sodium challenge with added sodium at 10 mEq/L,
but not at 20 mEq/L. Among five tested NaV channel subunits, NaV1.3 was highly
expressed in Lu-165 cells. However, phenytoin significantly decreased NaV1.3 mRNA
levels under the sodium challenge with added sodium at 10 and 20 mEq/L. These
results suggest that Lu-165 cells are sensitive to phenytoin and sodium to
control of AVP release and its gene expression. Phenytoin might have a direct
action on ectopic AVP-producing tumors, suggesting the importance of NaV channels
in AVP-producing neuroendocrine tumors.
PMID- 28503169
TI - Cytotoxicity, Intestinal Transport, and Bioavailability of Dispersible Iron and
Zinc Supplements.
AB - Iron or zinc deficiency is one of the most important nutritional disorders which
causes health problem. However, food fortification with minerals often induces
unacceptable organoleptic changes during preparation process and storage, has low
bioavailability and solubility, and is expensive. Nanotechnology surface
modification to obtain novel characteristics can be a useful tool to overcome
these problems. In this study, the efficacy and potential toxicity of dispersible
Fe or Zn supplement coated in dextrin and glycerides (SunActive FeTM and
SunActive ZnTM) were evaluated in terms of cytotoxicity, intestinal transport,
and bioavailability, as compared with each counterpart without coating, ferric
pyrophosphate (FePP) and zinc oxide (ZnO) nanoparticles (NPs), respectively. The
results demonstrate that the cytotoxicity of FePP was not significantly affected
by surface modification (SunActive FeTM), while SunActive ZnTM was more cytotoxic
than ZnO-NPs. Cellular uptake and intestinal transport efficiency of SunActive
FeTM were significantly higher than those of its counterpart material, which was
in good agreement with enhanced oral absorption efficacy after a single-dose oral
administration to rats. These results seem to be related to dissolution, particle
dispersibility, and coating stability of materials depending on suspending media.
Both SunActiveTM products and their counterpart materials were determined to be
primarily transported by microfold (M) cells through the intestinal epithelium.
It was, therefore, concluded that surface modification of food fortification will
be a useful strategy to enhance oral absorption efficiency at safe levels.
PMID- 28503167
TI - The Impact of Space Flight on Survival and Interaction of Cupriavidus
metallidurans CH34 with Basalt, a Volcanic Moon Analog Rock.
AB - Microbe-mineral interactions have become of interest for space exploration as
microorganisms could be used to biomine from extra-terrestrial material and
extract elements useful as micronutrients in life support systems. This research
aimed to identify the impact of space flight on the long-term survival of
Cupriavidus metallidurans CH34 in mineral water and the interaction with basalt,
a lunar-type rock in preparation for the ESA spaceflight experiment, BIOROCK.
Therefore, C. metallidurans CH34 cells were suspended in mineral water
supplemented with or without crushed basalt and send for 3 months on board the
Russian FOTON-M4 capsule. Long-term storage had a significant impact on cell
physiology and energy status (by flow cytometry analysis, plate count and
intracellular ATP measurements) as 60% of cells stored on ground lost their cell
membrane potential, only 17% were still active, average ATP levels per cell were
significantly lower and cultivability dropped to 1%. The cells stored in the
presence of basalt and exposed to space flight conditions during storage however
showed less dramatic changes in physiology, with only 16% of the cells lost their
cell membrane potential and 24% were still active, leading to a higher
cultivability (50%) and indicating a general positive effect of basalt and space
flight on survival. Microbe-mineral interactions and biofilm formation was
altered by spaceflight as less biofilm was formed on the basalt during flight
conditions. Leaching from basalt also changed (measured with ICP-OES), showing
that cells release more copper from basalt and the presence of cells also
impacted iron and magnesium concentration irrespective of the presence of basalt.
The flight conditions thus could counteract some of the detrimental effects
observed after the 3 month storage conditions.
PMID- 28503165
TI - Stress-Related and Circadian Secretion and Target Tissue Actions of
Glucocorticoids: Impact on Health.
AB - Living organisms are highly complex systems that must maintain a dynamic
equilibrium or homeostasis that requires energy to be sustained. Stress is a
state in which several extrinsic or intrinsic disturbing stimuli, the stressors,
threaten, or are perceived as threatening, homeostasis. To achieve homeostasis
against the stressors, organisms have developed a highly sophisticated system,
the stress system, which provides neuroendocrine adaptive responses, to restore
homeostasis. These responses must be appropriate in terms of size and/or
duration; otherwise, they may sustain life but be associated with detrimental
effects on numerous physiologic functions of the organism, leading to a state of
disease-causing disturbed homeostasis or cacostasis. In addition to facing a
broad spectrum of external and/or internal stressors, organisms are subject to
recurring environmental changes associated with the rotation of the planet around
itself and its revolution around the sun. To adjust their homeostasis and to
synchronize their activities to day/night cycles, organisms have developed an
evolutionarily conserved biologic system, the "clock" system, which influences
several physiologic functions in a circadian fashion. Accumulating evidence
suggests that the stress system is intimately related to the circadian clock
system, with dysfunction of the former resulting in dysregulation of the latter
and vice versa. In this review, we describe the functional components of the two
systems, we discuss their multilevel interactions, and we present how excessive
or prolonged activity of the stress system affects the circadian rhythm of
glucocorticoid secretion and target tissue effects.
PMID- 28503168
TI - Generation and Comprehensive Analysis of Host Cell Interactome of the PA Protein
of the Highly Pathogenic H5N1 Avian Influenza Virus in Mammalian Cells.
AB - Accumulating data have identified the important roles of PA protein in
replication and pathogenicity of influenza A virus (IAV). Identification of host
factors that interact with the PA protein may accelerate our understanding of IAV
pathogenesis. In this study, using immunoprecipitation assay combined with liquid
chromatography-tandem mass spectrometry, we identified 278 human cellular
proteins that might interact with PA of H5N1 IAV. Gene Ontology annotation
revealed that the identified proteins are highly associated with viral
translation and replication. Further KEGG pathway analysis of the interactome
profile highlighted cellular pathways associated with translation, infectious
disease, and signal transduction. In addition, Diseases and Functions analysis
suggested that these cellular proteins are highly related with Organismal Injury
and Abnormalities and Cell Death and Survival. Moreover, two cellular proteins
(nucleolin and eukaryotic translation elongation factor 1-alpha 1) identified
both in this study and others were further validated to interact with PA using co
immunoprecipitation and co-localization assays. Therefore, this study presented
the interactome data of H5N1 IAV PA protein in human cells which may provide
novel cellular target proteins for elucidating the potential molecular functions
of PA in regulating the lifecycle of IAV in human cells.
PMID- 28503170
TI - Drosophila melanogaster as a High-Throughput Model for Host-Microbiota
Interactions.
AB - Microbiota research often assumes that differences in abundance and identity of
microorganisms have unique influences on host physiology. To test this concept
mechanistically, germ-free mice are colonized with microbial communities to
assess causation. Due to the cost, infrastructure challenges, and time-consuming
nature of germ-free mouse models, an alternative approach is needed to
investigate host-microbial interactions. Drosophila melanogaster (fruit flies)
can be used as a high throughput in vivo screening model of host-microbiome
interactions as they are affordable, convenient, and replicable. D. melanogaster
were essential in discovering components of the innate immune response to
pathogens. However, axenic D. melanogaster can easily be generated for microbiome
studies without the need for ethical considerations. The simplified microbiota
structure enables researchers to evaluate permutations of how each microbial
species within the microbiota contribute to host phenotypes of interest. This
enables the possibility of thorough strain-level analysis of host and microbial
properties relevant to physiological outcomes. Moreover, a wide range of mutant
D. melanogaster strains can be affordably obtained from public stock centers.
Given this, D. melanogaster can be used to identify candidate mechanisms of host
microbe symbioses relevant to pathogen exclusion, innate immunity modulation,
diet, xenobiotics, and probiotic/prebiotic properties in a high throughput
manner. This perspective comments on the most promising areas of microbiota
research that could immediately benefit from using the D. melanogaster model.
PMID- 28503172
TI - Hydrocarbon Degradation in Caspian Sea Sediment Cores Subjected to Simulated
Petroleum Seepage in a Newly Designed Sediment-Oil-Flow-Through System.
AB - The microbial community response to petroleum seepage was investigated in a whole
round sediment core (16 cm length) collected nearby natural hydrocarbon seepage
structures in the Caspian Sea, using a newly developed Sediment-Oil-Flow-Through
(SOFT) system. Distinct redox zones established and migrated vertically in the
core during the 190 days-long simulated petroleum seepage. Methanogenic petroleum
degradation was indicated by an increase in methane concentration from 8 MUM in
an untreated core compared to 2300 MUM in the lower sulfate-free zone of the SOFT
core at the end of the experiment, accompanied by a respective decrease in the
delta13C signal of methane from -33.7 to -49.50/00. The involvement of
methanogens in petroleum degradation was further confirmed by methane production
in enrichment cultures from SOFT sediment after the addition of hexadecane,
methylnapthalene, toluene, and ethylbenzene. Petroleum degradation coupled to
sulfate reduction was indicated by the increase of integrated sulfate reduction
rates from 2.8 SO42-m-2 day-1 in untreated cores to 5.7 mmol SO42-m-2 day-1 in
the SOFT core at the end of the experiment, accompanied by a respective
accumulation of sulfide from 30 to 447 MUM. Volatile hydrocarbons (C2-C6 n
alkanes) passed through the methanogenic zone mostly unchanged and were depleted
within the sulfate-reducing zone. The amount of heavier n-alkanes (C10-C38)
decreased step-wise toward the top of the sediment core and a preferential
degradation of shorter (C30) was seen during
the seepage. This study illustrates, to the best of our knowledge, for the first
time the development of methanogenic petroleum degradation and the succession of
benthic microbial processes during petroleum passage in a whole round sediment
core.
PMID- 28503171
TI - Persistence of Salmonella Typhimurium LT2 in Soil Enhanced after Growth in
Lettuce Medium.
AB - The persistence of Salmonella in the environment is influenced by a multitude of
biotic and abiotic factors. In addition, its persistence can be influenced by
preadaptation before the introduction into the environment. In order to study how
preadaptation changes the survival of Salmonella in soil and therefore its
potential to colonize the phytosphere, we developed a new medium based on lettuce
material [lettuce medium (LM)]. Salmonella enterica serovar Typhimurium strain
LT2 was used as a model for Salmonella in this study. LT2 was inoculated into
soil microcosms after pregrowth in Luria Bertani (LB) broth or in LM. Survival of
LT2 in soil was monitored over 56 days by plate counts and quantification of the
Typhimurium-specific gene STM4497 using qPCR in total community DNA for which
primers and TaqMan probe were designed in this study. Significantly enhanced
persistence was observed for LT2 pregrown in LM compared to LT2 pregrown in LB,
indicating a preadaptation effect. Surprisingly, no improved survival could be
observed for S. Typhimurium strain 14028s and S. enterica serovar Senftenberg
after pregrowth on LM. This indicates a high strain specificity of preadaptation.
Results from previous studies suggested that biofilm formation could enhance the
survival of human pathogens in various environments and might contribute to
enhanced survival on plants. In vitro biofilm assays with several Salmonella
strains revealed a strain-specific effect of LM on the biofilm formation. While
LM significantly improved the biofilm formation of S. Senftenberg, the biofilm
formation of LT2 was better in LB. This indicates that the better survival of LM
pregrown LT2 in soil was not linked to an improved ability to form biofilms but
was likely due to other factors. Most importantly, this study showed that the
medium used to pregrow Salmonella can influence its survival in soil and its
biofilm formation which might influence the fate of Salmonella in soil.
PMID- 28503173
TI - Microbial Community Response to Simulated Petroleum Seepage in Caspian Sea
Sediments.
AB - Anaerobic microbial hydrocarbon degradation is a major biogeochemical process at
marine seeps. Here we studied the response of the microbial community to
petroleum seepage simulated for 190 days in a sediment core from the Caspian Sea
using a sediment-oil-flow-through (SOFT) system. Untreated (without simulated
petroleum seepage) and SOFT sediment microbial communities shared 43% bacterial
genus-level 16S rRNA-based operational taxonomic units (OTU0.945) but shared only
23% archaeal OTU0.945. The community differed significantly between sediment
layers. The detection of fourfold higher deltaproteobacterial cell numbers in
SOFT than in untreated sediment at depths characterized by highest sulfate
reduction rates and strongest decrease of gaseous and mid-chain alkane
concentrations indicated a specific response of hydrocarbon-degrading
Deltaproteobacteria. Based on an increase in specific CARD-FISH cell numbers, we
suggest the following groups of sulfate-reducing bacteria to be likely
responsible for the observed decrease in aliphatic and aromatic hydrocarbon
concentration in SOFT sediments: clade SCA1 for propane and butane degradation,
clade LCA2 for mid- to long-chain alkane degradation, clade Cyhx for
cycloalkanes, pentane and hexane degradation, and relatives of Desulfobacula for
toluene degradation. Highest numbers of archaea of the genus Methanosarcina were
found in the methanogenic zone of the SOFT core where we detected preferential
degradation of long-chain hydrocarbons. Sequencing of masD, a marker gene for
alkane degradation encoding (1-methylalkyl)succinate synthase, revealed a low
diversity in SOFT sediment with two abundant species-level MasD OTU0.96.
PMID- 28503174
TI - Commentary: Modification of Host Responses by Mycobacteria.
PMID- 28503175
TI - Heterogeneity of Phenotype and Function Reflects the Multistage Development of T
Follicular Helper Cells.
AB - T follicular helper cells (Tfh) provide crucial signals for germinal center (GC)
formation, but Tfh populations are heterogeneous. While PD1hi Tfh are important
in the GC response, the function of the PD1lo Tfh-like subset is unknown. We show
that these cells, like the PD1hi GC-Tfh, depend upon B cells; however, their
entry to follicles is independent of CXCR5 or cognate interactions with B cells.
The differentiation into PD1hi Tfh is dependent on MHC class II interactions with
B cells and requires CXCR5. Our data suggest a Tfh differentiation pathway that
is initially B cell-independent, then dependent on non-cognate B cell
interactions, and finally following cognate interaction with B cells and CXCR5
ligands allows the formation of GC-Tfh. The PD1lo Tfh-like cells make early
cytokine responses and may represent precursors of CD4 memory cells.
PMID- 28503176
TI - Impact of Autoantibodies against Glycolytic Enzymes on Pathogenicity of
Autoimmune Retinopathy and Other Autoimmune Disorders.
AB - Autoantibodies (AAbs) against glycolytic enzymes: aldolase, alpha-enolase,
glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase are prevalent in
sera of patients with blinding retinal diseases, such as paraneoplastic [cancer
associated retinopathy (CAR)] and non-paraneoplastic autoimmune retinopathies, as
well as in many other autoimmune diseases. CAR is a degenerative disease of the
retina characterized by sudden vision loss in patients with cancer and serum anti
retinal AAbs. In this review, we discuss the widespread serum presence of anti
glycolytic enzyme AAbs and their significance in autoimmune diseases. There are
multiple mechanisms responsible for antibody generation, including the innate
anti-microbial response, anti-tumor response, or autoimmune response against
released self-antigens from damaged, inflamed tissue. AAbs against enolase,
GADPH, and aldolase exist in a single patient in elevated titers, suggesting
their participation in pathogenicity. The lack of restriction of AAbs to one
disease may be related to an increased expression of glycolytic enzymes in
various metabolically active tissues that triggers an autoimmune response and
generation of AAbs with the same specificity in several chronic and autoimmune
conditions. In CAR, the importance of serum anti-glycolytic enzyme AAbs had been
previously dismissed, but the retina may be without pathological consequence
until a failure of the blood-retinal barrier function, which would then allow
pathogenic AAbs access to their retinal targets, ultimately leading to damaging
effects.
PMID- 28503177
TI - The Innate Immune Cross Talk between NK Cells and Eosinophils Is Regulated by the
Interaction of Natural Cytotoxicity Receptors with Eosinophil Surface Ligands.
AB - Previous studies suggested that the cross talk between NK cells and other cell
types is crucial for the regulation of both innate and adaptive immune responses.
In the present study, we analyzed the phenotypic and functional outcome of the
interaction between resting or cytokine-activated NK cells and eosinophils
derived from non-atopic donors. Our results provide the first evidence that a
natural cytotoxicity receptor (NCR)/NCR ligand-dependent cross talk between NK
cells and eosinophils may be important to upregulate the activation state and the
effector function of cytokine-primed NK cells. This interaction also promotes the
NK-mediated editing process of dendritic cells that influence the process of Th1
polarization. In turn, this cross talk also resulted in eosinophil activation and
acquisition of the characteristic features of antigen-presenting cells. At higher
NK/eosinophil ratios, cytokine-primed NK cells were found to kill eosinophils via
NKp46 and NKp30, thus suggesting a potential immunoregulatory role for NK cells
in dampening inflammatory responses involving eosinophils.
PMID- 28503178
TI - Transcriptomic Response of Chinese Yew (Taxus chinensis) to Cold Stress.
AB - Taxus chinensis is a rare and endangered shrub, highly sensitive to temperature
changes and widely known for its potential in cancer treatment. How gene
expression of T. chinensis responds to low temperature is still unknown. To
investigate cold response of the genus Taxus, we obtained the transcriptome
profiles of T. chinensis grown under normal and low temperature (cold stress, 0
degrees C) conditions using Illumina Miseq sequencing. A transcriptome including
83,963 transcripts and 62,654 genes were assembled from 4.16 Gb of reads data.
Comparative transcriptomic analysis identified 2,025 differently expressed (DE)
isoforms at p < 0.05, of which 1,437 were up-regulated by cold stress and 588
were down-regulated. Annotation of DE isoforms indicated that transcription
factors (TFs) in the MAPK signaling pathway and TF families of NAC, WRKY, bZIP,
MYB, and ERF were transcriptionally activated. This might have been caused by the
accumulation of secondary messengers, such as reactive oxygen species (ROS) and
Ca2+. While accumulation of ROS will have caused damages to cells, our results
indicated that to adapt to low temperatures T. chinensis employed a series of
mechanisms to minimize these damages. The mechanisms included: (i) cold-enhanced
expression of ROS deoxidant systems, such as peroxidase and phospholipid
hydroperoxide glutathione peroxidase, to remove ROS. This was further confirmed
by analyses showing increased activity of POD, SOD, and CAT under cold stress.
(ii) Activation of starch and sucrose metabolism, thiamine metabolism, and purine
metabolism by cold-stress to produce metabolites which either protect cell
organelles or lower the ROS content in cells. These processes are regulated by
ROS signaling, as the "feedback" toward ROS accumulation.
PMID- 28503179
TI - Molecular and Evolutionary Mechanisms of Cuticular Wax for Plant Drought
Tolerance.
AB - Cuticular wax, the first protective layer of above ground tissues of many plant
species, is a key evolutionary innovation in plants. Cuticular wax safeguards the
evolution from certain green algae to flowering plants and the diversification of
plant taxa during the eras of dry and adverse terrestrial living conditions and
global climate changes. Cuticular wax plays significant roles in plant abiotic
and biotic stress tolerance and has been implicated in defense mechanisms against
excessive ultraviolet radiation, high temperature, bacterial and fungal
pathogens, insects, high salinity, and low temperature. Drought, a major type of
abiotic stress, poses huge threats to global food security and health of
terrestrial ecosystem by limiting plant growth and crop productivity. The
composition, biochemistry, structure, biosynthesis, and transport of plant
cuticular wax have been reviewed extensively. However, the molecular and
evolutionary mechanisms of cuticular wax in plants in response to drought stress
are still lacking. In this review, we focus on potential mechanisms, from
evolutionary, molecular, and physiological aspects, that control cuticular wax
and its roles in plant drought tolerance. We also raise key research questions
and propose important directions to be resolved in the future, leading to
potential applications of cuticular wax for water use efficiency in agricultural
and environmental sustainability.
PMID- 28503181
TI - Development of a Critical Nitrogen Dilution Curve of Double Cropping Rice in
South China.
AB - The concept of critical nitrogen (Nc) concentration can be implemented to
diagnose in-season plant nitrogen (N) status for optimizing N fertilizer
management. The Nc dilution curves have been established for rice (Oryza sativa
L.) grown in different climatic regions, yet no attempt has been made to develop
the Nc dilution curve for double cropping rice regions. This study was undertaken
to develop the Nc dilution curves for double cropping rice in south China for
assessment of in-season N status and to establish the relationships N nutrition
index (NNI) and relative yield (RY) for in-season prediction of rice grain yield.
Three different N application rate field experiments using six Indica rice
varieties, including two early rice hybrids and four late rice hybrids were
carried out in east China. The Nc dilution curves based on whole plant N
concentration were determined and described as, Nc = 3.37 W-0.44 for early rice
and Nc = 3.69 W-0.34 for late rice. The constant N concentration at early growth
stage was 3.31 and 3.15% DM for early and late rice, respectively. Late rice
showed a higher capacity of N accumulation and a lower rate of N decline per unit
shoot biomass as compared to early rice. The curves for present study were
different from the existing reference curves for Indica and Japonica rice grown
in different rice growing regions. Integrated N nutrition index (NNIint) based on
Nc was used to estimate RY at different growth periods using linear regression
functions. The results showed that the critical curves and relationship between
NNIint and RY could be used as a reliable indicator of N status diagnosis, grain
yield prediction as well as to provide technical support in N management for
double cropping rice in south China.
PMID- 28503180
TI - Transcriptomic Comparison Reveals Candidate Genes for Triterpenoid Biosynthesis
in Two Closely Related Ilex Species.
AB - Native to Southern China, Ilex pubescens and Ilex asprella are frequently used in
traditional Chinese medicine. Both of them produce a large variety of ursane-type
triterpenoid saponins, which have been demonstrated to have different
pharmacological effects. However, little is known about their biosynthesis. In
this study, transcriptomic analysis of I. pubescens and comparison with its
closely related specie I. asprella were carried out to identify potential genes
involved in triterpenoid saponin biosynthesis. Through RNA sequencing (RNA-seq)
and de novo transcriptome assembly of I. pubescens, a total of 68,688 UniGene
clusters are obtained, of which 32,184 (46.86%) are successfully annotated by
comparison with the sequences in major public databases (NCBI, Swiss-Prot, and
KEGG). It includes 128 UniGenes related to triterpenoid backbone biosynthesis, 11
OSCs (oxidosqualene cyclases), 233 CYPs (cytochrome P450), and 269 UGTs (UDP
glycosyltransferases). By homology-based blast and phylogenetic analysis with
well-characterized genes involved in triterpenoid saponin biosynthesis, 5 OSCs,
14 CYPs, and 1 UGT are further proposed as the most promising candidate genes.
Transcriptomic comparison between two Ilex species using blastp and OrthoMCL
method reveals high sequence similarity. All OSCs and UGTs as well as most CYPs
are classified as orthologous genes, while only 5 CYPs in I. pubescens and 3 CYPs
in I. asprella are species-specific. One of OSC candidates, named as IpAS1, was
successfully cloned and expressed in Saccharomyces cerevisiae INVSc1. Analysis of
the yeast extract by gas chromatography (GC) and gas chromatography-mass
spectrometry (GC-MS) shows IpAS1 is a mixed amyrin synthase, producing alpha
amyrin and beta-amyrin at ratio of 5:1, which is similar to its ortholog IaAS1
from I. asprella. This study is the first exploration to profile the
transcriptome of I. pubescens, the generated data and gene models will facilitate
further molecular studies on the physiology and metabolism in this plant. By
comparative transcriptomic analysis, a series of candidate genes involved in the
biosynthetic pathway of triterpenoid saponins are identified, providing new
insight into their biosynthesis at transcriptome level.
PMID- 28503182
TI - Genome-Wide SNP Markers Based on SLAF-Seq Uncover Breeding Traces in Rapeseed
(Brassica napus L.).
AB - Single Nucleotide Polymorphisms (SNPs) are the most abundant and richest form of
genomic polymorphism, and hence make highly favorable markers for genetic map
construction and genome-wide association studies. In this study, a total of 300
rapeseed accessions (278 representative of Chinese germplasm, plus 22 outgroup
accessions of different origins and ecotypes) were collected and sequenced using
Specific-Locus Amplified Fragment Sequencing (SLAF-seq) technology, obtaining
660.25M reads with an average sequencing depth of 6.27 * and a mean Q30 of
85.96%. Based on the 238,711 polymorphic SLAF tags a total of 1,197,282 SNPs were
discovered, and a subset of 201,817 SNPs with minor allele frequency >0.05 and
integrity >0.8 were selected. Of these, 30,877 were designated SNP "hotspots,"
and 41 SNP-rich genomic regions could be delineated, with 100 genes associated
with plant resistance, vernalization response, and signal transduction detected
in these regions. Subsequent analysis of genetic diversity, linkage
disequilibrium (LD), and population structure in the 300 accessions was carried
out based on the 201,817 SNPs. Nine subpopulations were observed based on the
population structure analysis. Hierarchical clustering and principal component
analysis divided the 300 varieties roughly in accordance with their ecotype
origins. However, spring-type varieties were intermingled with semi-winter type
varieties, indicating frequent hybridization between spring and semi-winter
ecotypes in China. In addition, LD decay across the whole genome averaged 299 kb
when r2 = 0.1, but the LD decay in the A genome (43 kb) was much shorter than in
the C genome (1,455 kb), supporting the targeted introgression of the A genome
from progenitor species B. rapa into Chinese rapeseed. This study also lays the
foundation for genetic analysis of important agronomic traits using this rapeseed
population.
PMID- 28503185
TI - Phosphate Uptake from Phytate Due to Hyphae-Mediated Phytase Activity by
Arbuscular Mycorrhizal Maize.
AB - Phytate is the most abundant form of soil organic phosphorus (P). Increased P
nutrition of arbuscular mycorrhizal plants derived from phytate has been
repeatedly reported. Earlier studies assessed acid phosphatase rather than
phytase as an indication of mycorrhizal fungi-mediated phytate use. We
investigated the effect of mycorrhizal hyphae-mediated phytase activity on P
uptake by maize. Two maize (Zea mays L.) cultivars, non-inoculated or inoculated
with the arbuscular mycorrhizal fungi Funneliformis mosseae or Claroideoglomus
etunicatum, were grown for 45 days in two-compartment rhizoboxes, containing a
root compartment and a hyphal compartment. The soil in the hyphal compartment was
supplemented with 20, 100, and 200 mg P kg-1 soil as calcium phytate. We measured
activity of phytase and acid phosphatase in the hyphal compartment, hyphal length
density, P uptake, and plant biomass. Our results showed: (1) phytate addition
increased phytase and acid phosphatase activity, and resulted in larger P uptake
and plant biomass; (2) increases in P uptake and biomass were correlated with
phytase activity but not with acid phosphatase activity; (3) lower phytate
addition rate increased, but higher addition rate decreased hyphal length
density. We conclude that P from phytate can be taken up by arbuscular
mycorrhizal plants and that phytase plays a more important role in mineralizing
phytate than acid phosphatase.
PMID- 28503183
TI - Embolized Stems Recover Overnight in Zea mays: The Role of Soil Water, Root
Pressure, and Nighttime Transpiration.
AB - It is not currently well-understood how much xylem conductance is lost in maize
plants during the day, if conductance is recovered during the night, or what soil
water conditions are required for recovery to take place. To answer these
questions we designed a greenhouse experiment whereby two genetically dissimilar
maize genotypes were subjected to a level of water stress commonly experienced in
the field (Psixylem ~-2 MPa). We then measured the loss of stem-specific
conductivity associated with this level of stress, as well as the overnight
recovery following three re-watering treatments: Psisoil ~ 0 MPa, Psisoil ~-0.40
MPa, and Psisoil ~-1.70 MPa. Mid-day leaf water potentials of -1.98 MPa resulted
in stem-specific conductivity (KS) values that were 31.5% of maximal (i.e., 68%
loss). Returning soils to field capacity (Psisoil ~ 0 MPa) overnight allowed for
the significant recovery of KS (76% of maximal), whereas partial watering
(Psisoil ~-0.40 MPa) resulted KS values that were 51.7% of maximal values,
whereas not watering resulted in no recovery (35.4% of maximal; Psisoil ~-1.7
MPa). Recovery of KS was facilitated by the generation of root pressure and low
rates of nighttime transpiration.
PMID- 28503184
TI - An ABC Transporter Is Involved in the Silicon-Induced Formation of Casparian
Bands in the Exodermis of Rice.
AB - Silicon (Si) promotes the formation of Casparian bands (CB) in rice and reduces
radial oxygen loss (ROL). Further transcriptomic approaches revealed several
candidate genes involved in the Si-induced formation of CB such as ATP binding
cassette (ABC) transporter, Class III peroxidases, ligases and transferases.
Investigation of these genes by means of overexpression (OE) and knockout (KO)
mutants revealed the contribution of the ABC transporter (OsABCG25) to CB
formation in the exodermis, which was also reflected in the expression of other
OsABCG25 in the Si-promoted formation of CB genes related to the phenylpropanoid
pathway, such as phenylalanine-ammonia-lyase, diacylglycerol O-acyltransferase
and 4-coumarate-CoA ligase. Differential CB development in mutants and Si supply
also affected the barrier function of the exodermis. OE of the ABC transporter
and Si supply reduced the ROL from roots and Fe uptake. No effect on ROL and Fe
uptake could be observed for the KO mutant. The presented research confirms the
impact of the OsABCG25 in the Si-promoted formation of CB and its barrier
functions.
PMID- 28503186
TI - The Pepper RING Finger E3 Ligase, CaDIR1, Regulates the Drought Stress Response
via ABA-Mediated Signaling.
AB - Drought stress from soil or air limits plant growth and development, leading to a
reduction in crop productivity. Several E3 ligases positively or negatively
regulate the drought stress response. In the present study, we show that the
pepper (Capsicum annuum) Drought Induced RING type E3 ligase 1, CaDIR1, regulates
the drought stress response via abscisic acid (ABA)-mediated signaling. CaDIR1
contains a C3HC4-type RING finger domain in the N-terminal region; this domain
functions during protein degradation via attachment of ubiquitins to the
substrate target proteins. The expression levels of the CaDIR1 gene were
suppressed and induced by ABA and drought treatments, respectively. We conducted
loss-of-function and gain-of function genetic studies to examine the in vivo
function of CaDIR1 in response to ABA and drought stress. CaDIR1-silenced pepper
plants displayed a drought-tolerant phenotype characterized by a low level of
transpirational water loss via increased stomatal closure and elevated leaf
temperatures. CaDIR1-overexpressing (OX) Arabidopsis plants exhibited an ABA
hypersensitive phenotype during the germination stage, but an ABA-hyposensitive
phenotype-characterized by decreased stomatal closure and reduced leaf
temperatures-at the adult stage. Moreover, adult CaDIR1-OX plants exhibited a
drought-sensitive phenotype characterized by high levels of transpirational water
loss. Our results indicate that CaDIR1 functions as a negative regulator of the
drought stress response via ABA-mediated signaling. Our findings provide a
valuable insight into the plant defense mechanism that operates during drought
stress.
PMID- 28503187
TI - Worker reproduction of the invasive yellow crazy ant Anoplolepis gracilipes.
AB - BACKGROUND: Reproductive division of labor is one of the key features of social
insects. Queens are adapted for reproduction while workers are adapted for
foraging and colony maintenance. In many species, however, workers retain
functional ovaries and can lay unfertilized male eggs or trophic eggs. Here we
report for the first time on the occurrence of physogastric workers and apparent
worker reproduction in the invasive yellow crazy ant Anoplolepis gracilipes (Fr.
Smith). We further examined the reproductive potential and nutritional role of
physogastric workers through multidisciplinary approaches including morphological
characterization, laboratory manipulation, genetic analysis and behavioral
observation. RESULTS: Egg production with two types of eggs, namely reproductive
and trophic eggs, by physogastric workers was found. The reproductive egg was
confirmed to be haploid and male-destined, suggesting that the workers produced
males via arrhenotokous parthenogenesis as no spermatheca was discovered.
Detailed observations suggested that larvae were mainly fed with trophic eggs.
Along with consumption of trophic eggs by queens and other castes as part of
their diet, the vital role of physogastric workers as "trophic specialist" is
confirmed. CONCLUSION: We propose that adaptive advantages derived from worker
reproduction for A. gracilipes may include 1) trophic eggs provisioned by
physogastric workers likely assist colonies of A. gracilipes in overcoming
unfavorable conditions such as paucity of food during critical founding stage; 2)
worker-produced males are fertile and thus might offer an inclusive fitness
advantage for the doomed orphaned colony.
PMID- 28503188
TI - Impact of 8-week linoleic acid intake in soy oil on Lp-PLA2 activity in healthy
adults.
AB - BACKGROUND: No intervention follow-up study has examined the association between
plasma n-6 polyunsaturated fatty acids (PUFAs) and lipoprotein-associated
phospholipase A2 (Lp-PLA2), which is a risk factor for cardiovascular disease
(CVD). We aimed to determine whether the administration of linoleic acid (LA,
18:2n-6) in soy oil affected Lp-PLA2 activity in healthy adults. METHODS: Self
reported healthy participants (n = 150) were randomly assigned to three groups: a
low LA group, in which 10 mL soy oil was replaced with one apple; a medium LA
group, in which the typical food intake was maintained; and a high LA group, in
which 1/3 cup of cooked refined rice was replaced with 9.9 g of soy oil capsules
daily. Plasma fatty acids and Lp-PLA2 activity were measured along with other CVD
risk factors. RESULTS: After 8 weeks of treatment, plasma LA levels decreased in
the low LA group and increased in the high LA group. The high LA group showed
greater increases in apolipoprotein B (apoB) and oxidized low-density lipoprotein
(ox-LDL) than those in the low LA group. Plasma LA levels and Lp-PLA2 activities
demonstrated greater increases in the high LA group than those in the medium and
low LA groups. Changes in plasma LA positively and independently correlated with
changes in Lp-PLA2 activity, which was negatively correlated with changes in
collagen-epinephrine closure time (CEPI-CT). CONCLUSIONS: An increase in plasma
LA following intake of soy oil was independently associated with Lp-PLA2
activity, which was also related to apoB, ox-LDL and CEPI-CT. TRIAL REGISTRATION:
ClinicalTrail.gov Identifier: NCT02753907, registered 25 April 2016
(retrospectively registered).
PMID- 28503189
TI - Eicosapentaenoic acid shows anti-inflammatory effect via GPR120 in 3T3-L1
adipocytes and attenuates adipose tissue inflammation in diet-induced obese mice.
AB - BACKGROUND: Saturated fatty acids have been shown to cause insulin resistance and
low-grade chronic inflammation, whereas unsaturated fatty acids suppress
inflammation via G-protein coupled receptor 120 (GPR120) in macrophages. However,
the anti-inflammatory effects of unsaturated fatty acids in adipocytes have yet
to be elucidated. Hence, the aims of the present study were to evaluate the anti
inflammatory effects of eicosapentaenoic acid (EPA) via GPR120 in adipocytes.
METHODS: We used 250 MUM palmitate as a representative saturated fatty acid. 3T3
L1 adipocytes were used for in vitro studies. We further evaluated the effect of
EPA supplementation in a high-fat/high-sucrose (HFHS) diet-induced adipose tissue
inflammatory mouse model. RESULTS: EPA attenuated palmitate-induced increases in
inflammatory gene expression and NF-kappaB phosphorylation in 3T3-L1 adipocytes.
Silencing of GPR120 abolished the anti-inflammatory effects of EPA. In GPR120
downstream signal analysis, EPA was found to decrease palmitate-induced increases
in TAK1/TAB1 complex expression. EPA supplementation suppressed HFHS-induced
crown-like structure formation in epididymal adipose tissue and altered
macrophage phenotypes from M1 to M2 in the stromal vascular fraction. Moreover,
the EPA-containing diet attenuated increases in adipose p-JNK and phospho-p65 NF
kappaB levels. CONCLUSIONS: In conclusion, the findings of the present study
demonstrate that EPA suppresses palmitate-induced inflammation via GPR120 by
inhibiting the TAK1/TAB1 interaction in adipocytes. EPA supplementation reduced
HFHS diet-induced inflammatory changes in mouse adipose tissues. These results
demonstrate adipose GPR120 as a potential therapeutic target for decreasing
inflammation.
PMID- 28503190
TI - Essential amino acid ingestion alters expression of genes associated with amino
acid sensing, transport, and mTORC1 regulation in human skeletal muscle.
AB - BACKGROUND: Amino acid availability stimulates protein synthesis via the mTORC1
(mechanistic target of rapamycin complex 1) signaling pathway. In response to an
increase in cellular amino acid availability, translocation of cytosolic mTORC1
to the lysosomal surface is required to stimulate mTORC1 kinase activity.
However, research elucidating the amino acid responsive mechanisms have thus far
only been conducted in in vitro models. Our primary objective was to determine
whether an increase in amino acid availability within human skeletal muscle in
vivo would alter the expression of genes associated with amino acid sensing,
transport and mTORC1 regulation. Our secondary objective was to determine whether
an acute perturbation in lysosomal function would disrupt the normal pattern of
muscle amino acid responsive gene expression. METHODS: We recruited 13 young
adults into one of two groups: The first group ingested 10 g of essential amino
acids (EAA). The second group ingested 10 g of EAA in the presence of chloroquine
(CQ), a lysosomotropic agent. The subjects from each group had biopsies of the
vastus lateralis taken before and after EAA ingestion. We determined the relative
mRNA expression of 51 potential amino acid responsive genes using RT-qPCR.
RESULTS: There was a differential mRNA expression for 22 genes, with 15 mRNAs
significantly changing (P < 0.05) in response to EAA ingestion (e.g., REDD1: +209
+/- 35%; SLC38A9: +31 +/- 9%; SLC38A10: +57 +/- 15%). In the CQ group, EAA
ingestion resulted in a differential expression as compared to EAA alone (i.e.,
11 out of the 22 genes were different (P < 0.05) between the two groups.).
CONCLUSIONS: Expression of several amino acid sensing, transport, and mTORC1
regulatory genes in human skeletal muscle are responsive to an increase in amino
acid availability. Furthermore, potential acute disruption of lysosomal function
by ingestion of chloroquine interferes with the normal pattern of gene expression
following feeding. Our in vivo data in humans provide preliminary support for the
in vitro work linking amino acid sensing pathways to mTORC1 translocation to the
lysosome. TRIAL REGISTRATION: NCT00891696. Registered 29 April 2009.
PMID- 28503192
TI - The Potential for Youth Programs To Promote African American Youth's Development
of Ethnic and Racial Identity.
AB - Effective programs for youth can reduce problem behaviors and promote positive
development. In particular, cultural assets (e.g., ethnic-racial identity) are
important for African American youth's health and development. In this article,
we argue that youth programs represent an important social context for African
American youth's development of positive ethnic-racial identity and we present a
conceptual framework for understanding how such programs may affect African
American youth's development in this area. Then we provide examples of evidence
based programs that have assessed this developmental process among African
American youth. We conclude with considerations for research.
PMID- 28503191
TI - Breastfeeding the late preterm infant: experiences of mothers and perceptions of
public health nurses.
AB - BACKGROUND: The promotion and maintenance of breastfeeding with late preterm
infants (LPIs) remain under examined topics of study. This dearth of research
knowledge, especially for this population at-risk for various health
complications, requires scientific investigation. In this study, we explore the
experiences of mothers and the perceptions of public health nurses (PHNs) about
breastfeeding late preterm infants in Calgary, Alberta, Canada. METHODS: We used
an exploratory mixed methods design with a convenience sample of 122 mothers to
gather quantitative data about breastfeeding. We collected qualitative data by
means of individual face-to-face interviews with 11 mothers and 10 public health
nurses. Data were collected from April 2013 to June 2014. We then employed an
interpretive thematic analysis to identify central themes and relationships
across narratives. RESULTS: We collected 74 complete data sets about
breastfeeding. During the first 6-8 weeks postpartum, 61 mothers breastfed their
infants. Of these, 51 partially breastfed and 10 exclusively breastfed. For
qualitative purposes, the researchers interviewed 11 mothers with late preterm
babies and three themes emerged: significant difficulty with breastfeeding,
failing to recognize the infant's feeding distress and disorganized behavior, and
the parental stress caused by the multiple feeding issues. The public health
nurses' comments reinforced and expanded on what the mothers reported. The themes
for the nurses included: challenges with initiating breastfeeding, challenges
during breastfeeding, and the need for stimulation during breastfeeding.
CONCLUSION: Mothers face challenges when breastfeeding their late preterm infants
and public health nurses can guide them through this experience. Families with a
late preterm infant need to be informed about the challenges associated with
breastfeeding a late preterm infant. It is necessary for all health care
professionals to receive proper training on safe and effective breastfeeding of
late preterm infants. It is essential for public health nurses to communicate
effectively with families of late preterm infants to provide anticipatory
guidance about potential challenges and strategies to resolve any breastfeeding
problems.
PMID- 28503193
TI - Correlates, comorbidities, and suicidal tendencies of problematic game use in a
national wide sample of Korean adults.
AB - BACKGROUND: This study aimed to investigate the prevalence, correlates,
comorbidities, and suicidal tendencies of problematic game use in a nationally
representative sample of Korean adults. METHODS: Of the 6022 subjects who
participated in the 2011 Korean Epidemiologic Catchment Area study and completed
the Composite International Diagnostic Interview 2.1, 1397 game users were
evaluated for problematic game use using 9-item DSM-5 proposed criteria for
Internet gaming disorder. Respondents who responded "yes" to five or more of the
nine DSM-5 criteria were considered as problematic game users and the reminders
were considered as normal game users. RESULTS: 4.0% (56/1397) of game users were
classified as a problematic game user. Problematic game users were more likely to
be in younger age group and live in urban area compared with normal game user.
Problematic game use was positively associated with several psychiatric disorders
including nicotine use disorder, depressive disorder, and anxiety disorder, but
not associated with alcohol use disorder and obsessive-compulsive disorder, after
adjusting for age, sex, and residential area. Problematic game use was
significantly and positively associated with suicide plans, after controlling for
psychiatric disorders as well as socio-demographic factors. CONCLUSION:
Problematic game use is relatively prevalent in Korean adult population and
highly comorbid with other psychiatric disorders and suicidality. Therefore,
preventive strategy for problematic game use is needed for game users who were
more likely to be addicted such as young adults in urban area, and mental health
screening and appropriate treatment are needed for individuals with problematic
game use.
PMID- 28503195
TI - Strategies for improved isopropanol-butanol production by a Clostridium strain
from glucose and hemicellulose through consolidated bioprocessing.
AB - BACKGROUND: High cost of traditional substrates and formation of by-products
(such as acetone and ethanol) in acetone-butanol-ethanol (ABE) fermentation
hindered the large-scale production of biobutanol. Here, we comprehensively
characterized a newly isolated solventogenic and xylanolytic Clostridium species,
which could produce butanol at a high ratio with elimination of ethanol and
conversion of acetone to more value-added product, isopropanol. Ultimately,
direct butanol production from hemicellulose was achieved with efficient
expression of indigenous xylanase by the novel strain via consolidated
bioprocessing. RESULTS: A novel wild-type Clostridium sp. strain NJP7 was
isolated and characterized in this study, which was capable of fermenting
monosaccharides, e.g., glucose into butanol via a fermentative acetone
isopropanol-butanol pathway. With enhancement of buffering capacity and alcohol
dehydrogenase activities, butanol and isopropanol titer by Clostridium sp. strain
NJP7 was improved to 12.21 and 1.92 g/L, respectively, and solvent productivity
could be enhanced to 0.44 g/L/h. Furthermore, with in situ extraction with
biodiesel, the amount of butanol and isopropanol was finally improved to 25.58
and 5.25 g/L in the fed-batch mode. Meanwhile, Clostridium sp. strain NJP7 shows
capability of direct isopropanol-butanol production from hemicelluloses with
expression of indigenous xylanase. 2.06 g/L of butanol and 0.54 g/L of
isopropanol were finally achieved through the temperature-shift simultaneous
saccharification and fermentation, representing the highest butanol production
directly from hemicellulose. CONCLUSION: The co-production of isopropanol with
butanol by the newly isolated Clostridium sp. strain NJP7 would add on the
economical values for butanol fermentation. Furthermore, the high isopropanol
butanol production with in situ extraction would also greatly enhance the
economic feasibility for fermentative production of butanol-isopropanol in large
scale. Meanwhile, its direct production of butanol-isopropanol from
polysaccharides, hemicellulose through secretion of indigenous thermostable
xylanase, shows great potential using lignocellulosic wastes for biofuel
production.
PMID- 28503194
TI - What are effective strategies for implementing trauma-informed care in youth
inpatient psychiatric and residential treatment settings? A realist systematic
review.
AB - BACKGROUND: Many young people who receive psychiatric care in inpatient or
residential settings in North America have experienced various forms of emotional
trauma. Moreover, these settings can exacerbate trauma sequelae. Common
practices, such as seclusion and restraint, put young people at risk of
retraumatization, development of comorbid psychopathology, injury, and even
death. In response, psychiatric and residential facilities have embraced trauma
informed care (TIC), an organizational change strategy which aligns service
delivery with treatment principles and discrete interventions designed to reduce
rates of retraumatization through responsive and non-coercive staff-client
interactions. After more than two decades, a number of TIC frameworks and
approaches have shown favorable results. Largely unexamined, however, are the
features that lead to successful implementation of TIC, especially in child and
adolescent inpatient psychiatric and residential settings. METHODS: Using methods
proposed by Pawson et al. (J Health Serv Res Policy 10:21-34, 2005), we conducted
a modified five-stage realist systematic review of peer-reviewed TIC literature.
We rigorously searched ten electronic databases for peer reviewed publications
appearing between 2000 and 2015 linking terms "trauma-informed" and "child*" or
"youth," plus "inpatient" or "residential" plus "psych*" or "mental." After
screening 693 unique abstracts, we selected 13 articles which described TIC
interventions in youth psychiatric or residential settings. We designed a
theoretically-based evaluative framework using the active implementation cycles
of the National Implementation Research Network (NIRN) to discern which foci were
associated with effective TIC implementation. Excluded were statewide mental
health initiatives and TIC implementations in outpatient mental health, child
welfare, and education settings. Interventions examined included: Attachment,
Self-Regulation, and Competency Framework; Six Core Strategies; Collaborative
Problem Solving; Sanctuary Model; Risking Connection; and the Fairy Tale Model.
RESULTS: Five factors were instrumental in implementing trauma informed care
across a spectrum of initiatives: senior leadership commitment, sufficient staff
support, amplifying the voices of patients and families, aligning policy and
programming with trauma informed principles, and using data to help motivate
change. CONCLUSIONS: Reduction or elimination of coercive measures may be
achieved by explicitly targeting specific coercive measures or by implementing
broader therapeutic models. Additional research is needed to evaluate the
efficacy of both approaches.
PMID- 28503196
TI - Synthesis and analysis of separation networks for the recovery of intracellular
chemicals generated from microbial-based conversions.
AB - BACKGROUND: Bioseparations can contribute to more than 70% in the total
production cost of a bio-based chemical, and if the desired chemical is localized
intracellularly, there can be additional challenges associated with its recovery.
Based on the properties of the desired chemical and other components in the
stream, there can be multiple feasible options for product recovery. These
options are composed of several alternative technologies, performing similar
tasks. The suitability of a technology for a particular chemical depends on (1)
its performance parameters, such as separation efficiency; (2) cost or amount of
added separating agent; (3) properties of the bioreactor effluent (e.g., biomass
titer, product content); and (4) final product specifications. Our goal is to
first synthesize alternative separation options and then analyze how technology
selection affects the overall process economics. To achieve this, we propose an
optimization-based framework that helps in identifying the critical technologies
and parameters. RESULTS: We study the separation networks for two representative
classes of chemicals based on their properties. The separation network is divided
into three stages: cell and product isolation (stage I), product concentration
(II), and product purification and refining (III). Each stage exploits
differences in specific product properties for achieving the desired product
quality. The cost contribution analysis for the two cases (intracellular
insoluble and intracellular soluble) reveals that stage I is the key cost
contributor (>70% of the overall cost). Further analysis suggests that changes in
input conditions and technology performance parameters lead to new designs
primarily in stage I. CONCLUSIONS: The proposed framework provides significant
insights for technology selection and assists in making informed decisions
regarding technologies that should be used in combination for a given set of
stream/product properties and final output specifications. Additionally, the
parametric sensitivity provides an opportunity to make crucial design and
selection decisions in a comprehensive and rational manner. This will prove
valuable in the selection of chemicals to be produced using bioconversions
(bioproducts) as well as in creating better bioseparation flow sheets for
detailed economic assessment and process implementation on the commercial scale.
PMID- 28503197
TI - The significance of proline and glutamate on butanol chaotropic stress in
Bacillus subtilis 168.
AB - BACKGROUND: Butanol is an intensively used industrial solvent and an attractive
alternative biofuel, but the bioproduction suffers from its high toxicity. Among
the native butanol producers and heterologous butanol-producing hosts, Bacillus
subtilis 168 exhibited relatively higher butanol tolerance. Nevertheless, organic
solvent tolerance mechanisms in Bacilli and Gram-positive bacteria have
relatively less information. Thus, this study aimed to elucidate butanol stress
responses that may involve in unique tolerance of B. subtilis 168 to butanol and
other alcohol biocommodities. RESULTS: Using comparative proteomics approach and
molecular analysis of butanol-challenged B. subtilis 168, 108 butanol-responsive
proteins were revealed, and classified into seven groups according to their
biological functions. While parts of them may be similar to the proteins
reportedly involved in solvent stress response in other Gram-positive bacteria,
significant role of proline in the proline-glutamate-arginine metabolism was
substantiated. Detection of intracellular proline and glutamate accumulation, as
well as glutamate transient conversion during butanol exposure confirmed their
necessity, especially proline, for cellular butanol tolerance. Disruption of the
particular genes in proline biosynthesis pathways clarified the essential role of
the anabolic ProB-ProA-ProI system over the osmoadaptive ProH-ProA-ProJ system
for cellular protection in response to butanol exposure. Molecular modifications
to increase gene dosage for proline biosynthesis as well as for glutamate
acquisition enhanced butanol tolerance of B. subtilis 168 up to 1.8% (vol/vol)
under the conditions tested. CONCLUSION: This work revealed the important role of
proline as an effective compatible solute that is required to protect cells
against butanol chaotropic effect and to maintain cellular functions in B.
subtilis 168 during butanol exposure. Nevertheless, the accumulation of
intracellular proline against butanol stress required a metabolic conversion of
glutamate through the specific biosynthetic ProB-ProA-ProI route. Thus, exogenous
addition of glutamate, but not proline, enhanced butanol tolerance. These
findings serve as a practical knowledge to enhance B. subtilis 168 butanol
tolerance, and demonstrate means to engineer the bacterial host to promote higher
butanol/alcohol tolerance of B. subtilis 168 for the production of butanol and
other alcohol biocommodities.
PMID- 28503198
TI - Dynamics of two methanogenic microbiomes incubated in polycyclic aromatic
hydrocarbons, naphthenic acids, and oil field produced water.
AB - BACKGROUND: Oil field produced water (OFPW) is widely produced in large volumes
around the world. Transforming the organic matter in OFPW into bioenergy, such as
biomethane, is one promising way to sustainability. However, OFPW is difficult to
biologically degrade because it contains complex compounds such as naphthenic
acids (NAs), or polycyclic aromatic hydrocarbons (PAHs). Although active
microbial communities have been found in many oil reservoirs, little is known
about how an exotic microbiome, e.g. the one which originates from municipal
wastewater treatment plants, would evolve when incubated with OFPW. RESULTS: In
this study, we harvested methanogenic biomass from two sources: a full-scale
anaerobic digester (AD) treating oil and gas processing wastewater (named O&G
sludge), and from a full-scale AD reactor treating multiple fractions of
municipal solid wastes (named MS, short for mixed sludge). Both were incubated in
replicate microcosms fed with PAHs, NAs, or OFPW. The results showed that the
PAHs, NAs, and OFPW feeds could rapidly alter the methanogenic microbiomes, even
after 14 days, while the O&G sludge adapted faster than the mixed sludge in all
the incubations. Two rarely reported microorganisms, a hydrogenotrophic
methanogen Candidatus methanoregula and a saccharolytic fermenter Kosmotoga, were
found to be prevalent in the PAHs and OFPW microcosms, and are likely to play an
important role in the syntrophic degradation of PAHs and OFPW, cooperating with
methanogens such as Methanoregula, Methanosarcina, or Methanobacterium.
CONCLUSIONS: The dominant phyla varied in certain patterns during the
incubations, depending on the biomass source, feed type, and variation in
nutrients. The sludge that originated from the oil and gas processing wastewater
treatment (O&G) reactor adapted faster than the one from municipal solid waste
reactors, almost certainly because the O&G biomass had been "pre-selected" by the
environment. This study reveals the importance of biomass selection for other
crude oil-waste-related bioengineering studies, such as bioaugmentation and
bioremediation.
PMID- 28503199
TI - The "Aachen fall prevention App" - a Smartphone application app for the self
assessment of elderly patients at risk for ground level falls.
AB - BACKGROUND: Fall incidents are a major problem for patients and healthcare. The
"Aachen Fall Prevention App" (AFPA) represents the first mobile Health (mHealth)
application (app) empowering older patients (persons 50+ years) to self-assess
and monitor their individual fall risk. Self-assessment is based on the "Aachen
Fall Prevention Scale," which consists of three steps. First, patients answer ten
standardized yes-no questions (positive criterion >= 5 "Yes" responses). Second,
a ten-second test of free standing without compensatory movement is performed
(positive criterion: compensatory movement). Finally, during the third step,
patients rate their subjective fall risk on a 10-point Likert scale, based on the
results of steps one and two. The purpose of this app is (1) to offer a low
threshold service through which individuals can independently monitor their
individual fall risk and (2) to collect data about how a patient-centered mHealth
app for fall risk assessment is used in the field. RESULTS: The results represent
the first year of an ongoing field study. From December 2015 to December 2016,
197 persons downloaded the AFPA (iOSTM and AndroidTM; free of charge). N = 111 of
these persons voluntarily shared their data and thereby participated in the field
study. Data from a final number of n = 79 persons were analyzed due to exclusion
criteria (age, missing objective fall risk, missing self-assessment). The
objective fall risk and the self-assessed subjective risk measured by the AFPA
showed a significant positive relationship. CONCLUSIONS: The "Aachen Fall
Prevention App" (AFPA) is an mHealth app released for iOS and Android. This field
study revealed the AFPA as a promising tool to raise older adults' awareness of
their individual fall risk by means of a low-threshold patient-driven fall risk
assessment tool.
PMID- 28503200
TI - A retrospective cohort study of adverse events in patients undergoing orthopaedic
surgery.
AB - BACKGROUND: This study's objective was to identify adverse events following
common orthopaedic procedures, and to estimate the incidence rates and risks of
these events and their associations with age, sex, and comorbidities. METHODS:
This retrospective cohort study manually reviewed and extracted electronic
medical data on the incidence and predictors of adverse events that occurred
within 90 days of the 50 most frequent orthopaedic surgeries at an academic
hospital in 2010. We also extracted demographic data, baseline comorbidities, and
duration of follow-up (<=90 days). Patients were scored on the Charlson
Comorbidity Index (CCI) and the Functional Comorbidity Index (FCI). We estimated
incidence rates and risks for all events and associations using regression
methods. Prolonged pain 42-days post-surgery was treated as a separate outcome.
RESULTS: We included 1,552 patients; average age was 53.4 years, and 51.7% were
female. A total of 1,148 adverse events were identified in 729 patients. The
incidence rate of all adverse events was 10 events per 1,000 person-days at risk;
47% of all patients experienced at least one adverse event within 90 days. The
most frequent events were prolonged pain (31% of all adverse events) and
persistent swelling (7%). We found positive associations between both comorbidity
scores and the incidence rate and 90-day risk of all adverse events, excluding
pain, adjusting for age and sex (neither of which was associated with adverse
events); the association was stronger for the FCI than for the CCI. For total hip
arthroplasty (THA) and total knee arthroplasty (TKA), the incidence rate of all
adverse events, excluding pain, was positively associated with both comorbidity
scores and age; the 90-day risk was positively associate with the FCI score and
male sex. The prevalence of prolonged pain at 42 days was greater in patients
with higher FCI scores; for THA and TKA only, pain prevalence was greater in
those with higher FCI scores and in men. CONCLUSIONS: Adverse events are frequent
following common orthopaedic procedures. The incidence is greatest for patients
with more functional comorbidities. For THA and TKA procedures, being male and
being older are also associated with a greater incidence of adverse events.
PMID- 28503201
TI - DNA methylation and DNA methyltransferases.
AB - The prevailing views as to the form, function, and regulation of genomic
methylation patterns have their origin many years in the past, at a time when the
structure of the mammalian genome was only dimly perceived, when the number of
protein-encoding mammalian genes was believed to be at least five times greater
than the actual number, and when it was not understood that only ~10% of the
genome is under selective pressure and likely to have biological function. We use
more recent findings from genome biology and whole-genome methylation profiling
to provide a reappraisal of the shape of genomic methylation patterns and the
nature of the changes that they undergo during gametogenesis and early
development. We observe that the sequences that undergo deep changes in
methylation status during early development are largely sequences without
regulatory function. We also discuss recent findings that begin to explain the
remarkable fidelity of maintenance methylation. Rather than a general overview of
DNA methylation in mammals (which has been the subject of many reviews), we
present a new analysis of the distribution of methylated CpG dinucleotides across
the multiple sequence compartments that make up the mammalian genome, and we
offer an updated interpretation of the nature of the changes in methylation
patterns that occur in germ cells and early embryos. We discuss the cues that
might designate specific sequences for demethylation or de novo methylation
during development, and we summarize recent findings on mechanisms that maintain
methylation patterns in mammalian genomes. We also describe the several human
disorders, each very different from the other, that are caused by mutations in
DNA methyltransferase genes.
PMID- 28503203
TI - Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and
applications.
AB - Fluorescent carbon dots (FCDs) are an emerging class of nanomaterials made from
carbon sources that have been hailed as potential non-toxic replacements to
traditional semiconductor quantum dots (QDs). Particularly in the areas of live
imaging and drug delivery, due to their water solubility, low toxicity and photo-
and chemical stability. Carbohydrates are readily available chiral biomolecules
in nature which offer an attractive and cheap starting material from which to
synthesise FCDs with distinct features and interesting applications. This mini
review article will cover the progress in the development of FCDs prepared from
carbohydrate sources with an emphasis on their synthesis, functionalization and
technical applications, including discussions on current challenges.
PMID- 28503202
TI - Stabilization of Foxp3 expression by CRISPR-dCas9-based epigenome editing in
mouse primary T cells.
AB - BACKGROUND: Epigenome editing is expected to manipulate transcription and cell
fates and to elucidate the gene expression mechanisms in various cell types. For
functional epigenome editing, assessing the chromatin context-dependent activity
of artificial epigenetic modifier is required. RESULTS: In this study, we applied
clustered regularly interspaced short palindromic repeats (CRISPR)-dCas9-based
epigenome editing to mouse primary T cells, focusing on the Forkhead box P3
(Foxp3) gene locus, a master transcription factor of regulatory T cells (Tregs).
The Foxp3 gene locus is regulated by combinatorial epigenetic modifications,
which determine the Foxp3 expression. Foxp3 expression is unstable in
transforming growth factor beta (TGF-beta)-induced Tregs (iTregs), while stable
in thymus-derived Tregs (tTregs). To stabilize Foxp3 expression in iTregs, we
introduced dCas9-TET1CD (dCas9 fused to the catalytic domain (CD) of ten-eleven
translocation dioxygenase 1 (TET1), methylcytosine dioxygenase) and dCas9-p300CD
(dCas9 fused to the CD of p300, histone acetyltransferase) with guide RNAs
(gRNAs) targeted to the Foxp3 gene locus. Although dCas9-TET1CD induced partial
demethylation in enhancer region called conserved non-coding DNA sequences 2
(CNS2), robust Foxp3 stabilization was not observed. In contrast, dCas9-p300CD
targeted to the promoter locus partly maintained Foxp3 transcription in cultured
and primary T cells even under inflammatory conditions in vitro. Furthermore,
dCas9-p300CD promoted expression of Treg signature genes and enhanced suppression
activity in vitro. CONCLUSIONS: Our results showed that artificial epigenome
editing modified the epigenetic status and gene expression of the targeted loci,
and engineered cellular functions in conjunction with endogenous epigenetic
modification, suggesting effective usage of these technologies, which help
elucidate the relationship between chromatin states and gene expression.
PMID- 28503205
TI - Substitution of fluorine in M[C6F5BF3] with organolithium compounds: distinctions
between O- and N-nucleophiles.
AB - Borates M[C6F5BF3] (M = K, Li, Bu4N) react with organolithium compounds, RLi (R =
Me, Bu, Ph), in 1,2-dimethoxyethane or diglyme to give M[4-RC6F4BF3] and M[2
RC6F4BF3]. When R is Me or Bu, the nucleophilic substitution of the fluorine atom
at the para position to boron is the predominant route. When R = Ph, the ratio
M[4-RC6F4BF3]/M[2-RC6F4BF3] is ca. 1:1. Substitution of the fluorine atom at the
ortho position to boron is solely caused by the coordination of RLi via the
lithium atom with the fluorine atoms of the BF3 group. This differs from the
previously reported substitution in K[C6F5BF3] by O- and N-nucleophiles that did
not produce K[2-NuC6F4BF3].
PMID- 28503204
TI - Ultrasound-promoted organocatalytic enamine-azide [3 + 2] cycloaddition reactions
for the synthesis of ((arylselanyl)phenyl-1H-1,2,3-triazol-4-yl)ketones.
AB - The use of sonochemistry is described in the organocatalytic enamine-azide [3 +
2] cycloaddition between 1,3-diketones and aryl azidophenyl selenides. These
sonochemically promoted reactions were found to be amenable to a range of 1,3
diketones or aryl azidophenyl selenides, providing an efficient access to new
((arylselanyl)phenyl-1H-1,2,3-triazol-4-yl)ketones in good to excellent yields
and short reaction times. In addition, this protocol was extended to beta-keto
esters, beta-keto amides and alpha-cyano ketones. Selanyltriazoyl carboxylates,
carboxamides and carbonitriles were synthesized in high yields at short times of
reaction under very mild reaction conditions.
PMID- 28503206
TI - Inclusion complexes of beta-cyclodextrin with tricyclic drugs: an X-ray
diffraction, NMR and molecular dynamics study.
AB - Tricyclic fused-ring cyclobenzaprine (1) and amitriptyline (2) form 1:1 inclusion
complexes with beta-cyclodextrin (beta-CD) in the solid state and in water
solution. Rotating frame NOE experiments (ROESY) showed the same geometry of
inclusion for both 1/beta-CD and 2/beta-CD complexes, with the aromatic ring
system entering the cavity from the large rim of the cyclodextrin and the
alkylammonium chain protruding out of the cavity and facing the secondary OH rim.
These features matched those found in the molecular dynamics (MD) simulations in
solution and in the solid state from single-crystal X-ray diffraction of 1/beta
CD and 2/beta-CD complexes. The latter complex was found in a single conformation
in the solid state, whilst the MD simulations in explicit water reproduced the
conformational transitions observed experimentally for the free molecule.
PMID- 28503207
TI - Membrane properties of hydroxycholesterols related to the brain cholesterol
metabolism.
AB - Compared to cholesterol, hydroxycholesterols contain an additional hydroxy group
in the alkyl chain and are able to efficiently cross the brain-blood barrier.
Therefore, they are responsible for the sterol transfer between brain and
circulation. The current study compares the membrane properties of several
hydroxycholesterols with those of cholesterol using 2H NMR spectroscopy, a
membrane permeability assay, and fluorescence microscopy experiments. It is shown
that hydroxycholesterols do not exert the unique impact on membrane properties
characteristic for cholesterol with regard to the influence on lipid chain order,
membrane permeability and formation of lateral domains.
PMID- 28503208
TI - Fluorinated cyclohexanes: Synthesis of amine building blocks of the all-cis
2,3,5,6-tetrafluorocyclohexylamine motif.
AB - This paper reports the synthesis of three amine stereoisomers 5a-c of the
tetrafluorocyclohexyl ring system, as building blocks for discovery chemistry
programmes. The synthesis starts from a Birch reduction of benzonitrile, followed
by an in situ methyl iodide quench. The resultant 2,5-cyclohexadiene was
progressed via double epoxidations and then hydrofluorination ring opening
reactions. The resultant fluorohydrin moieties were then converted to different
stereoisomers of the tetrafluorocyclohexyl ring system, and then reductive
hydrogenation of the nitrile delivered three amine stereoisomers. It proved
necessary to place a methyl group on the cyclohexane ring in order to stabilise
the compound against subsequent HF elimination. The two all-cis
tetrafluorocyclohexyl isomers 5a and 5b constitute facially polarized cyclohexane
rings, with fluorines on the electronegative face and hydrogens on the
electropositive face.
PMID- 28503209
TI - Continuous-flow processes for the catalytic partial hydrogenation reaction of
alkynes.
AB - The catalytic partial hydrogenation of substituted alkynes to alkenes is a
process of high importance in the manufacture of several market chemicals. The
present paper shortly reviews the heterogeneous catalytic systems engineered for
this reaction under continuous flow and in the liquid phase. The main
contributions appeared in the literature from 1997 up to August 2016 are
discussed in terms of reactor design. A comparison with batch and industrial
processes is provided whenever possible.
PMID- 28503210
TI - Synthesis of ribavirin 2'-Me-C-nucleoside analogues.
AB - An efficient synthetic pathway leading to two carbonated analogues of ribavirin
is described. The key-steps in the synthesis of these ribosyltriazoles bearing a
quaternary carbon atom in the 2'-position are an indium-mediated alkynylation and
a 1,3-dipolar cyclization.
PMID- 28503211
TI - Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel
mouse and human analysis.
AB - BACKGROUND: Clinicians have qualitatively described rhythmic delta activity as a
prominent EEG abnormality in individuals with Angelman syndrome, but this
phenotype has yet to be rigorously quantified in the clinical population or
validated in a preclinical model. Here, we sought to quantitatively measure delta
rhythmicity and evaluate its fidelity as a biomarker. METHODS: We quantified
delta oscillations in mouse and human using parallel spectral analysis methods
and measured regional, state-specific, and developmental changes in delta rhythms
in a patient population. RESULTS: Delta power was broadly increased and more
dynamic in both the Angelman syndrome mouse model, relative to wild-type
littermates, and in children with Angelman syndrome, relative to age-matched
neurotypical controls. Enhanced delta oscillations in children with Angelman
syndrome were present during wakefulness and sleep, were generalized across the
neocortex, and were more pronounced at earlier ages. CONCLUSIONS: Delta
rhythmicity phenotypes can serve as reliable biomarkers for Angelman syndrome in
both preclinical and clinical settings.
PMID- 28503213
TI - Epigenetic modifications of the immune-checkpoint genes CTLA4 and PDCD1 in non
small cell lung cancer results in increased expression.
AB - Targeting checkpoint inhibitors using monoclonal antibodies results in
significantly better outcome of cancer patients compared to conventional
chemotherapy. However, the current companion diagnostics to predict response is
so far suboptimal, since they base on more or less reliable immunohistochemical
approaches. In order to overcome these limitations, we analyzed epigenetic
modifications of PDCD1 (PD1), CD274 (PD-L1), and CTLA4 in NSCLC tissues from 39
patients. Results were correlated with transcriptome data. Significant
differences in the CpG-methylation patterns between tumor tissues and matched
controls were observed for CTLA4 and PDCD1 (PD1) showing a decreased methylation
of these genes compared to matched tumor-free tissues from the same patients.
Results were confirmed by bisulfide sequencing in an independent validation
cohort. Hypomethylation also resulted in increased expression of these genes as
shown by transcriptome data. These epigenetic pathways as a hallmark of NSCLC
might be useful to generate more precise diagnostic approaches in the future.
PMID- 28503215
TI - Fast determination of structurally cohesive subgroups in large networks.
AB - Structurally cohesive subgroups are a powerful and mathematically rigorous way to
characterize network robustness. Their strength lies in the ability to detect
strong connections among vertices that not only have no neighbors in common, but
that may be distantly separated in the graph. Unfortunately, identifying cohesive
subgroups is a computationally intensive problem, which has limited empirical
assessments of cohesion to relatively small graphs of at most a few thousand
vertices. We describe here an approach that exploits the properties of cliques, k
cores and vertex separators to iteratively reduce the complexity of the graph to
the point where standard algorithms can be used to complete the analysis. As a
proof of principle, we apply our method to the cohesion analysis of a 29,462
vertex biconnected component extracted from a 128,151-vertex co-authorship data
set.
PMID- 28503212
TI - Associations between maternal risk factors of adverse pregnancy and birth
outcomes and the offspring epigenetic clock of gestational age at birth.
AB - BACKGROUND: A recent study has shown that it is possible to accurately estimate
gestational age (GA) at birth from the DNA methylation (DNAm) of fetal umbilical
cord blood/newborn blood spots. This DNAm GA predictor may provide additional
information relevant to developmental stage. In 814 mother-neonate pairs, we
evaluated the associations between DNAm GA and a number of maternal and offspring
characteristics. These characteristics reflect prenatal environmental adversity
and are expected to influence newborn developmental stage. RESULTS: DNAm GA
acceleration (GAA; i.e., older DNAm GA than chronological GA) of the offspring at
birth was associated with maternal age of over 40 years at delivery, pre
eclampsia and fetal demise in a previous pregnancy, maternal pre-eclampsia and
treatment with antenatal betamethasone in the index pregnancy, lower neonatal
birth size, lower 1-min Apgar score, and female sex. DNAm GA deceleration (GAD;
i.e., younger DNAm GA than chronological GA) of the offspring at birth was
associated with insulin-treated gestational diabetes mellitus (GDM) in a previous
pregnancy and Sjogren's syndrome. These findings were more accentuated when the
DNAm GA calculation was based on the raw difference between DNAm GA and GA than
on the residual from the linear regression of DNAm GA on GA. CONCLUSIONS: Our
findings show that variations in the DNAm GA of the offspring at birth are
associated with a number of maternal and offspring characteristics known to
reflect exposure to prenatal environmental adversity. Future studies should be
aimed at determining if this biological variation is predictive of developmental
adversity.
PMID- 28503216
TI - Public knowledge, attitudes and practices regarding antibiotic use in Kosovo.
AB - BACKGROUND: Antimicrobial resistance is becoming a major public health challenge
worldwide, caused primarily by the misuse of antibiotics. Antibiotic use is
closely related to the knowledge, attitudes and behaviour of a population.
OBJECTIVE: The objective of this study was to assess the level of knowledge,
attitudes and practices about antibiotic use among the general public in Kosovo.
METHODS: A cross-sectional face-to-face survey was carried out with a sample of
811 randomly selected Kosovo residents. The methodology used for this survey was
based on the European Commission Eurobarometer survey on antimicrobial
resistance. RESULTS: More than half of respondents (58.7%) have used antibiotics
during the past year. A quarter of respondents consumed antibiotics without a
medical prescription. The most common reasons for usage were flu (23.8%),
followed by sore throat (20.2%), cold (13%) and common cold (7.6%). 42.5% of
respondents think that antibiotics are effective against viral infections. Almost
half of respondents (46.7%) received information about the unnecessary use of
antibiotics and 32.5% of them report having changed their views and behaviours
after receiving this information. Health care workers were identified as the most
trustworthy source of information on antibiotic use (67.2%). CONCLUSION: These
results provide quantitative baseline data on Kosovar knowledge, attitudes and
practice regarding the use of antibiotic. These findings have potential to
empower educational campaigns to promote the prudent use of antibiotics in both
community and health care settings.
PMID- 28503217
TI - Assessment and use of drug information references in Utah pharmacies.
AB - OBJECTIVE: To determine which drug references Utah pharmacists use most
frequently. To determine which types of drug information questions are most
commonly asked, and whether Utah pharmacists have access to adequate references
to respond to these questions. METHODS: A 19-question survey was created using
Qualtrics, LLC (Provo, Utah) software. An electronic survey link was sent to
1,431 pharmacists with a valid e-mail address listed in the Department of
Professional Licensing database. Questions focused on available references in the
participant's pharmacy, how current the references are, and the participant's use
of the references. Surveys were analyzed for participants practicing in either
community or hospital pharmacies in the state of Utah. RESULTS: A total of 147
responses were included in the analysis. Approximately 44% of respondents
practiced in the community, and 56% practiced in a hospital setting. The most
commonly used references by Utah pharmacists are Micromedex, Lexicomp, UpToDate,
Clinical Pharmacology, and Drug Facts & Comparisons. Pharmacists in the community
frequently receive questions related to adverse drug reactions, drug
interactions, and over-the-counter medications. Pharmacists in the hospital
frequently receive questions relating to dosage and administration, drug
interactions, and adverse drug reactions. About 89% of community pharmacists and
96% of hospital pharmacists feel available references are adequate to answer the
questions they receive. CONCLUSIONS: Utah pharmacists generally use large
reference suites to answer drug information questions. The majority of
pharmacists consider the references available to them to be adequate to answer
the questions they receive.
PMID- 28503214
TI - Management of Resistant, Atypical and Culture-negative Periprosthetic Joint
Infections after Hip and Knee Arthroplasty.
AB - BACKGROUND: Periprosthetic joint infection (PJI) is a devastating complication
following lower extremity total joint arthroplasty (TJA). It is a leading cause
of morbidity and revision following TJA. As such, PJI is a significant driver of
healthcare costs. The prevalence of PJI related to resistant and atypical
organisms is increasing, and approximately 10-30% of PJIs are culture-negative.
The purpose of this review is to summarize the current epidemiology, diagnostics,
and management of PJI associated with resistant and atypical pathogens and of
culture-negative PJIs. METHODS: The published literature related to the
epidemiology, diagnosis, and management of atypical, drug-resistant, and culture
negative PJI is reviewed. RESULTS: The clinical diagnosis of PJI is often
challenging, particularly when pathogens are fastidious or when antibiotics have
been administered empirically. Molecular diagnostic studies, such as synovial
alpha-defensin, may provide rapid, accurate identification of PJI, even in the
setting of concurrent antibiotics administration or systemic inflammatory
disease. Once PJI is diagnosed, two-stage exchange arthroplasty remains the gold
standard for treating PJI with resistant microorganisms, since there is a high
rate of treatment failure with irrigation and debridement and with one-stage
exchange arthroplasty. CONCLUSION: Additional research is needed to define the
optimal treatment of PJIs associated with rare pathogens, such as fungi and
mycobacteria. There is a need for inexpensive, reliable tests that rapidly detect
specific microbial species and antimicrobial susceptibilities. Additional
research is also required to define the specific organisms, clinical scenarios,
surgical techniques, and antimicrobial regimens that allow for reproducible
treatment success with prosthetic retention strategies.
PMID- 28503218
TI - Impact of value added services on patient waiting time at the ambulatory pharmacy
Queen Elizabeth Hospital.
AB - BACKGROUND: Value added services (VAS) are an innovative dispensing system
created to provide an alternative means of collecting partial drug supply from
our hospital. This in turn was projected to reduce the necessity for patient to
visit pharmacy counter and thus reduce the burden of prescription handling.
OBJECTIVE: To evaluate the impact of increased VAS uptake following promotional
campaign towards patient waiting time and to explore factors that may affect
patient waiting time at the Ambulatory Pharmacy, Queen Elizabeth Hospital.
METHODS: A quasi experimental study design was conducted from September 2014 till
June 2015 at the Ambulatory Pharmacy. During pre-intervention phase, baseline
parameters were collected retrospectively. Then, VAS promotional campaign was
carried out for six months and whilst this was done, the primary outcome of
patient waiting time was measured by percentage of prescription served less than
30 minutes. A linear regression analysis was used to determine the impact of
increased VAS uptake towards patient waiting time. RESULTS: An increased in
percentage of VAS registration (20.9% vs 35.7%, p<0.001) was observed after the
promotional campaign. The mean percentage of prescription served less than 30
minutes increased from 83.2% SD=15.9 to 90.3% SD=11.5, p=0.001. After controlling
for covariates, it was found that patient waiting time was affected by number of
pharmacy technicians (b=-0.0349, 95%CI-0.0548 : -0.0150, p=0.001), number of
pharmacy counters (b=0.1125, 95%CI 0.0631 : 0.1620, p<0.001), number of
prescriptions (b=0.0008, 95%CI 0.0004 : 0.0011, p<0.001), and number of refill
prescriptions (b=0.0004, 95%CI 0.0002 : 0.0007, p<0.001). The increased in
percentage of VAS registration was associated with reduction in number of refill
prescription (b=-2.9838, 95%CI -4.2289 : -1.7388, p<0.001). CONCLUSIONS: Patient
waiting time at the Ambulatory Pharmacy improved with the increased in VAS
registration. The impact of increased VAS uptake on patient waiting time resulted
from reduction in refill prescriptions. Patient waiting time is influenced by
number of pharmacy technicians, number of pharmacy counters, number of
prescriptions and number of refill prescriptions.
PMID- 28503219
TI - Situation analysis of community pharmacy owners in Lebanon.
AB - OBJECTIVE: To evaluate the current community pharmacists' interventions and job
satisfaction, secondary to the alteration in the financial rewards. METHODS: A
cross-sectional study was carried out, using a proportionate random sample of
Lebanese community pharmacy owners from all districts of Lebanon. RESULTS: Out of
1618 distributed questionnaires, 1465 (90.5%) were collected back from pharmacy
owners. Our study results showed that the monthly sales and profit decreased
significantly in the last decade as well as the number of loyal customers
(p<0.001 for all). The rent, the total assistant pharmacists' and employees'
salaries, income taxes, municipality fees, the total bills (electricity, water,
cleaning, security) and the disposal of expired products per year significantly
increased during the last 10 years (p<0.001). 95% of the owners said they cannot
afford to hire any more pharmacists while 45% said they cannot afford buying
software for their pharmacies. Finally, 89% of these owners admitted that their
situation was better 10 years ago compared to nowadays. CONCLUSION: Most Lebanese
community pharmacists are not financially satisfied; their financial situation
deteriorated in the last decade. The ministry of Health along with the Order of
Pharmacists in Lebanon should cooperate together to resolve this problem since
they are two entities responsible for the patient's health.
PMID- 28503220
TI - Medication reconciliation errors in a tertiary care hospital in Saudi Arabia:
admission discrepancies and risk factors.
AB - BACKGROUND: Medication reconciliation is a major component of safe patient care.
One of the main problems in the implementation of a medication reconciliation
process is the lack of human resources. With limited resources, it is better to
target medication reconciliation resources to patients who will derive the most
benefit from it. OBJECTIVE: The primary objective of this study was to determine
the frequency and types of medication reconciliation errors identified by
pharmacists performing medication reconciliation at admission. Each medication
error was rated for its potential to cause patient harm during hospitalization. A
secondary objective was to determine risk factors associated with medication
reconciliation errors. METHODS: This was a prospective, single-center pilot study
conducted in the internal medicine and surgical wards of a tertiary care teaching
hospital in the Eastern province of Saudi Arabia. A clinical pharmacist took the
best possible medication history of patients admitted to medical and surgical
services and compared with the medication orders at hospital admission; any
identified discrepancies were noted and analyzed for reconciliation errors.
Multivariate logistic regression was performed to determine the risk factors
related to reconciliation errors. RESULTS: A total of 328 patients (138 in
surgical and 198 in medical) were included in the study. For the 1419 medications
recorded, 1091 discrepancies were discovered out of which 491 (41.6%) were
reconciliation errors. The errors affected 177 patients (54%). The incidence of
reconciliation errors in the medical patient group was 25.1% and 32.0% in the
surgical group (p<0.001). In both groups, the most frequent reconciliation error
was the omission (43.5% and 51.2%). Lipid-lowering (12.4%) and antihypertensive
agents were most commonly involved. If undetected, 43.6% of order errors were
rated as potentially requiring increased monitoring or intervention to preclude
harm; 17.7% were rated as potentially harmful. A multivariate logistic regression
model showed that patients aged >=65 years, polypharmacy, and prescriptions for
hypoglycemic drugs and warfarin were more likely associated with reconciliation
errors. CONCLUSION: There is a high failure rate in medication reconciliation
process in patients admitted to the medical and surgical department. The
reconciliation process proves to be a useful tool since nearly half of avoided
reconciliation errors were unintentional and had the potential for harm. This
strategy, based on our results and the difficulty of applying the process to all
patients should be directed primarily to the patients at increased risk of error.
PMID- 28503221
TI - Management of musculoskeletal pain in retail drug outlets within a Nigerian
community: a descriptive study.
AB - OBJECTIVE: This work aimed to describe attitudes and practices of both community
pharmacies and patent and proprietary medicine vendor (PPMV) outlets towards over
the-counter (OTC) analgesic use for musculoskeletal pain states within Zaria,
Nigeria. METHODS: The study was carried out in 2 phases from May to August 2016.
Phase one was a cross-sectional survey of 40 retail drug outlets (10 community
pharmacies and 30 PPMVs). A simulated patient scenario of a young adult male
complaining of acute onset back pain was used to collect data on the type and
quality of analgesic recommended, duration of consultation, as well as nature of
information provided during the drug dispensing process. The second phase
involved semi structured interviews with 7 drug vendors (4 pharmacists and 3
patent medicine vendors). The interviewees were asked questions to assess their
knowledge of analgesics as well as what type of analgesic they would recommend in
three hypothetical patient scenarios. RESULTS: A wide variety of therapeutic
agents were recommended for the simulated patient. Majority of these drugs were
oral analgesics and contained NSAIDS either alone or in combination. Less than
half of both patent medicine outlets and pharmacies (26.7% and 40% respectively)
provided the simulated patient with information on duration of therapy, and asked
the patient questions about their past medical and medication history (30% and
33.3% respectively). All analgesics purchased from the pharmacies were registered
with the Nigerian drug regulatory agency and had expiry dates compared to only
66.7% and 90% of those bought from patent medicine outlets. Interviewed drug
vendors admitted to obtaining a large amount of their knowledge on analgesics
from drug information leaflets and prior learning. They also showed some
knowledge deficits when questioned on side effects of analgesics and appropriate
drug selection in the hypothetical scenarios. CONCLUSIONS: There are problems
with both the OTC analgesics recommended, and the counselling provided for these
medicines by drug vendors within the Zaria community. While both pharmacies and
patent medicine outlets had shortcomings in several of the areas assessed by the
simulated patient, the pharmacies performed better.
PMID- 28503222
TI - Olanzapine for chemotherapy-induced nausea and vomiting: systematic review and
meta-analysis.
AB - BACKGROUND: Chemotherapy induced nausea and vomiting (CINV) remains the most
distressing event in patients receiving highly emetogenic chemotherapy (HEC) or
moderately emetogenic chemotherapy (MEC). OBJECTIVE: Therefore, this meta
analysis was conducted to evaluate the efficacy of olanzapine containing regimen
in preventing acute, delayed and overall phases of CINV. METHODS: PubMed, EBSCO,
and Cochrane central register of controlled trials electronic databases were
searched to identify RCTs that compared the effects of olanzapine with non
olanzapine regimen in preventing CINV. Randomized clinical trials (RCTs) that
compared olanzapine containing regimen with non-olanzapine regimen were included.
The primary outcomes were the percentage of patients achieving no vomiting or no
nausea in acute, delayed and overall phases. RESULTS: 13 RCTs that enrolled 1686
participants were included in this meta-analysis. 852 patients were assigned to
olanzapine and 834 patients were assigned to non-olanzapine regimen (other
standard antiemetic regimen). The percentages of no emesis achieved were 87.5%,
76.2%, 73.6% in olanzapine versus 76.7%, 61.8%, and 56.4% in non-olanzapine
regimen in acute, delayed and overall phases, respectively. The percentages of no
nausea were 82%, 64.3%, 61.6% in olanzapine group versus 71.3%, 41.8%, and 40.6%
in non-olanzapine group in acute, delayed and overall phases, respectively. In
general, olanzapine containing regimen achieved statistical superiority to non
olanzapine regimen in no vomiting endpoint in acute phase (OR 2.16; 95%CI 1.60 to
2.91, p<0.00001; I-square=5%; p=0.40), delayed phase (OR 2.28; 95%CI 1.1.46 to
3.54, p=0.0003; I-square=65%; p=0.001) and overall phase (OR 2.48; 95%CI 1.59 to
3.86, p<0.0001; I-square=69%; p< 0.0001). CONCLUSION: The current meta-analysis
showed that olanzapine was statistically and clinically superior to non
olanzapine regimen in preventing CINV in most domains of the parameters.
PMID- 28503223
TI - Hospital and community pharmacists' perception of the scope, barriers and
challenges of pharmacy practice-based research in Nigeria.
AB - OBJECTIVES: To evaluate perception, extent of involvement and barriers to
pharmacy practice-based research among community and hospital pharmacists in
Ibadan, Oyo state, southwestern Nigeria. METHODS: A prospective cross-sectional
study was carried out among 65 hospital and 86 community pharmacists with at
least five-year post-qualification experience, using pre-tested questionnaire.
Socio-demographic information, extent of involvement, relevance and scope, as
well as barriers to pharmacy practice-based research were explored. Data were
summarised using descriptive statistics. Kruskal-Wallis and Mann-Whitney-U tests
were used for evaluating ranked variables at p<0.05. RESULTS: Nearly all
participants (>95.0%) in each practice category agreed that pharmacy practice
based research is essential to pharmacy profession. Greater than 90.0% agreed
that pharmacy practice-based research may help in identifying gaps to improve
practice. Thirty-five (40.7%) community and 36(55.4%) hospital pharmacist
participants had previously involved in practice-based research. Seventy-seven
(89.5%) community and 55(84.3%) hospital pharmacists agreed that acquisition of
additional research-oriented training is essential for effective conduct of
pharmacy practice-based research. More than one-half in each category agreed that
inadequate financial commitment and lack of access to patient's data are major
barriers to pharmacy practice-based research. CONCLUSIONS: Community and hospital
pharmacists agreed that pharmacy practice based research is essential to pharmacy
profession, especially in identifying areas of focus to improve practice.
Necessity for acquiring additional training in research, financial constraints
and lack of access to patient's data were identified as barriers to pharmacy
practice-based research. Thus, there is a need to continually stimulate
pharmacists' interest in research so as to enhance professional competence and
promote healthcare development.
PMID- 28503224
TI - Psychometric properties of the Belief about Medicines Questionnaire (BMQ) in the
Maltese language.
AB - BACKGROUND: Investigating beliefs about medicines has been of interest over the
past years, with studies aiming to better understand theoretical reasons behind
development of such beliefs. OBJECTIVE: This study aimed to produce a culturally
and contextually appropriate version of the Beliefs about Medicines Questionnaire
(BMQ) in the Maltese language and to assess its psychometric properties. METHODS:
Medication beliefs were evaluated using the BMQ which is divided into two
sections: BMQ-General (sub-scales: Overuse and Harm, 4 items per sub-scale) and
BMQ-Specific (sub-scales: Necessity and Concerns, 5 items per sub-scale).
Following translation/back translation, the Maltese version of the BMQ was
applied to patients having asthma, diabetes, cardiovascular disease or depression
who attended out-patients' clinics at the main state general hospital in Malta
between June and September 2013. Cronbach's alpha coefficient, alpha, was used to
determine internal consistency of the BMQ and Principal Component Analysis using
Varimax rotation with Kaiser normalisation was carried out to analyse component
loading of the items on the respective sub-scales. RESULTS: The Maltese version
of the BMQ showed acceptable internal consistency for the harm scale
(alpha=0.56), the necessity scale (alpha=0.73) and the concerns scale
(alpha=0.66), however the overuse scale gave poor internal consistency
(alpha=0.48) due to the item on natural remedies which posed some difficulty in
the Maltese sample. The final solution for Principal Component Analysis yielded a
four-factor structure representing the 4 sub-scales of the BMQ, with results
being comparable to previous studies out in different languages. CONCLUSION: The
Maltese version of the BMQ was found to have acceptable psychometric properties
for the beliefs about medicines in the Maltese population.
PMID- 28503225
TI - Self-reported and actual involvement of community pharmacists in patient
counseling: a cross-sectional and simulated patient study in Gondar, Ethiopia.
AB - BACKGROUND: Community pharmacists play a crucial role in reducing medication
related health problems and improving the patient's overall wellbeing. Evidence
suggests that community pharmacist led counseling services result in a better
clinical and self-reported outcome, including a higher level of satisfaction and
quality of life. OBJECTIVE: This study aims to document self-reported and actual
levels of community pharmacists' involvement in the provision of patient
counseling and barriers that limit their involvement in such services. METHODS:
Simulated patient visits and a cross-sectional survey of community pharmacists
were employed in Gondar town, Ethiopia between March 15 and May 15, 2016 to
observe actual counseling practices and to assess their reported counseling
practices respectively. Four different scenarios were developed for the simulated
patient visit. A well designed questionnaire and an assessment form were used for
the survey and simulated patient visit. RESULTS: In the cross-sectional survey,
84 pharmacists were approached and 78 agreed to participate (92.8 % response
rate). Of the respondents, 96.1% agreed/strongly agreed that patient counseling
is important and 69.3% strongly agreed that patient counseling should be a
professional duty. The most frequent information provided to patients were dosing
schedule of drugs, how to take medication, and drug-food interaction. Majority of
community pharmacists either strongly agreed (42.1%) or agreed (51.3%) that
patients are comfortable towards their counseling practice. A total of 48
simulated visits were conducted and a medicine was dispensed in all visits. In
all four scenarios, dosage schedule (100%), how to take medication (97.6%) and
drug-food interaction (69.1%) were the most common type of information provided
while what to do when dose is missed (100%), contraindication (95.2%) and the
importance of compliance or adherence (92.9%) were the most commonly ignored
types of information. CONCLUSIONS: The present study emphasizes the existing gap
in self-reported and actual counseling practices by community pharmacist in
Gondar town, Ethiopia. Hence, the ministry of health, local health policy makers
and other stakeholders should collaborate to design interventions to improve
community pharmacists' dispensing and counseling practice.
PMID- 28503226
TI - Consumer views on safety of over-the-counter drugs, preferred retailers and
information sources in Sweden: after re-regulation of the pharmacy market.
AB - BACKGROUND: The availability of over-the-counter drugs (OTCs) has increased in
Sweden since a re-regulation of the pharmacy market in 2009, through which non
pharmacy retailers became permitted to provide certain OTCs. OBJECTIVE: To
examine the adult general public's views on safety, purchasing and information
channels, storage and disposal of OTCs in Sweden, three years after the re
regulation of the pharmacy market. METHODS: A questionnaire study in 2012-13 in a
stratified, random sample of all inhabitants in Sweden >= 18 years old. RESULTS:
Totally 8,302 people (42%) answered the questionnaire. Seven percent found OTCs
completely harmless regardless of how they are being used, 18% felt they should
be used only on health professionals' recommendation. Differences in how OTCs are
perceived were however found with regards to respondents' country of birth,
family type, educational level and income. The pharmacy was still the preferred
OTC drug retailer by 83% of the respondents and preferred information source by
80% Reasons for preferred retailers were primarily due to out of habit (45%),
counseling provided (35%), the product range (34%) and the confidence in staff
(27%). Analgesics are the most common OTCs to have at home (90%). The bathroom
cabinet is the primary site for storage (42%) and 16% throw their OTC leftovers
in the trash. CONCLUSIONS: The study population does not consider OTCs as
harmless regardless of how they are used, but on the other hand feels they should
not be taken on health professionals' recommendation only. The pharmacy is still
the preferred retailer and information source, and there is room for further
improvement in the storage and disposal of OTCs. A return of OTC drug leftovers
to the pharmacy should be further encouraged. Due to several limitations, great
caution should however be observed when generalizing the results to the adult
population of Sweden.
PMID- 28503227
TI - Relationship between pharmacy residency examination rank and specialty choice for
French pharmacy residency-admitted students.
AB - OBJECTIVE: To analyze the link between the rank at the national pharmacy
residency examination and the choice of pharmacy specialty for hospital residency
admitted French pharmacy students. METHODS: Examination ranks as well as the
pharmacy residency specialty to which residency candidates are finally admitted
were collected for all students (n=1948) having successfully passed the national
French pharmacy residency examination over the period 2013-2016. Students were
categorized by their pharmacy specialty for residency, i.e., "Medical Biology"
(n=591), "Hospital Pharmacy" (n=1175) and "Pharmaceutical Innovation and
Research" (n=182), and medians of examination ranks as well as limit ranks (the
rank of the last admitted postulant) by specialty were compared. RESULTS:
Examination ranks for pharmacy residency-admitted students were found to
significantly differ according to the nature of the specialty in which students
were finally admitted. "Medical Biology" has the lowest examination ranks (and
appears thus as the most selective specialty), followed by "Hospital Pharmacy"
and ended by "Pharmaceutical Innovation and Research", that has the highest
examination ranks (and appears thus as the least selective specialty). Limit
examination ranks were additionally shown to discriminate university hospitals in
which residents were assigned. CONCLUSION: Specialty choice for hospital
residency-admitted French pharmacy candidates is closely associated with their
rank at the national pharmacy residency examination, which can be assumed as
reflecting their academic level. By this way, an implicit hierarchy of French
pharmacy residency specialties according to the academic level of postulants can
likely be drawn.
PMID- 28503228
TI - Network meta-analysis: a technique to gather evidence from direct and indirect
comparisons.
AB - Systematic reviews and pairwise meta-analyses of randomized controlled trials, at
the intersection of clinical medicine, epidemiology and statistics, are
positioned at the top of evidence-based practice hierarchy. These are important
tools to base drugs approval, clinical protocols and guidelines formulation and
for decision-making. However, this traditional technique only partially yield
information that clinicians, patients and policy-makers need to make informed
decisions, since it usually compares only two interventions at the time. In the
market, regardless the clinical condition under evaluation, usually many
interventions are available and few of them have been studied in head-to-head
studies. This scenario precludes conclusions to be drawn from comparisons of all
interventions profile (e.g. efficacy and safety). The recent development and
introduction of a new technique - usually referred as network meta-analysis,
indirect meta-analysis, multiple or mixed treatment comparisons - has allowed the
estimation of metrics for all possible comparisons in the same model,
simultaneously gathering direct and indirect evidence. Over the last years this
statistical tool has matured as technique with models available for all types of
raw data, producing different pooled effect measures, using both Frequentist and
Bayesian frameworks, with different software packages. However, the conduction,
report and interpretation of network meta-analysis still poses multiple
challenges that should be carefully considered, especially because this technique
inherits all assumptions from pairwise meta-analysis but with increased
complexity. Thus, we aim to provide a basic explanation of network meta-analysis
conduction, highlighting its risks and benefits for evidence-based practice,
including information on statistical methods evolution, assumptions and steps for
performing the analysis.
PMID- 28503230
TI - Utility of preoperative 3 Tesla pelvic phased-array multiparametric magnetic
resonance imaging in prediction of extracapsular extension and seminal vesicle
invasion of prostate cancer and its impact on surgical margin status: Experience
at a Canadian academic tertiary care centre.
AB - INTRODUCTION: To evaluate the utility of 3 Tesla (3T) pelvic phased-array (PPA)
multiparametric magnetic resonance imaging (mpMRI) to predict extracapsular
extension (ECE) and seminal vesicle invasion (SVI) and its subsequent effect on
radical prostatectomy (RP) surgical margin status. METHODS: A retrospective
evaluation was conducted of RP patients who underwent preoperative 3T PPA mpMRI
(without endorectal coil) based on clinical probability of adverse pathological
features. Frequencies, specificity, sensitivity, positive predictive value (PPV),
and negative predictive value (NPV) of mpMRI in predicting the status of ECE and
SVI were calculated. RESULTS: Forty-eight consecutive patients were included.
Sensitivity, specificity, PPV, and NPV for 3T PPA mpMRI using T2-weighted
sequences with diffusion-weighted imaging (DWI) and dynamic contrast enhanced
(DCE) imaging to predict ECE was 39%, 56%, 45%, and 50%, respectively, while SVI
prediction was 33%, 95%, 50%, and 91%, respectively. Twelve of the 28 cases
predicted as being negative for ECE had positive margins, while two of the 20
cases predicted to be positive for ECE had positive margins. Imaging predicted
four cases would have SVI, yet two had positive margins, while of the 44 cases
predicted as being negative for SVI, four had positive margins. CONCLUSIONS:
These findings at our centre suggest that the use of 3T PPA mpMRI using T2
weighted sequences with DWI and DCE in predicting pathological ECE and SVI is of
questionable benefit. These mpMRI reports may result in closer dissection of
neurovascular bundles and subsequent positive surgical margins. Caution should be
exercised when basing intraoperative decisions on mpMRI findings.
PMID- 28503231
TI - OnabotulinumtoxinA for the treatment of idiopathic overactive bladder is
effective and safe for repeated use.
AB - INTRODUCTION: The objective of this study was to compare efficacy and safety
outcomes between patients receiving onabotulinum-toxinA (OnabotA) for the first
time and those receiving a repeat injection. METHODS: Data collected before and
after OnabotA injection were extracted from a clinical registry. Patients were
classified into either first or repeat injection subgroups. Efficacy was measured
by the change in use of oral bladder medications, the number of voids per day or
night, the frequency of urinary incontinence (UI) episodes, and patient-reported
outcomes. Safety was measured by the number of self-reported complications.
Differences in safety measures between the subgroups were tested. RESULTS: The
analysis included complete data from 81 patients; 30 (37%) receiving OnabotA for
the first time, 51 (63%) receiving a repeat injection. Both subgroups reported
significant reductions in the use of anticholinergics, more tolerable bladder
symptoms, and improvements in patient-reported outcomes. Dry rates were similarly
high in both groups (50% and 43%, respectively). There were no statistically
significant differences between the subgroups in terms of their safety outcomes.
CONCLUSIONS: OnabotA is equally as efficacious and safe for patients with
overactive bladder receiving a repeat injection as it is for those receiving
their first injection.
PMID- 28503232
TI - Cytoreductive nephrectomy in the modern era: Predictors of use, morbidity, and
survival.
AB - INTRODUCTION: To determine tumour, patient, and provider factors associated with
cytoreductive nephrectomy (CN) use and to identify those factors that predicted
short-term and long-term surgical outcomes. METHODS: We performed a retrospective
review (1998-2011) of the National Cancer Database, a U.S. population-based
oncology outcomes database. The review included 36 549 patients with metastatic
renal cell carcinoma (mRCC). We assessed predictors of CN use, length of stay
(LOS), 30-day readmission, and 30-day mortality using multivariable logistic
regression. The Cox proportional hazards model assessed predictors of overall
survival (OS). RESULTS: Overall, 10 809 (29.6%) patients received CN, increasing
from 15.2% to 36.1% over time. Private insurance (odds ratio [OR] 1.26; 95%
confidence interval [CI] 1.16-1.37) and academic facilities (OR 1.83; 95% CI 1.68
1.99) were associated with receiving CN (p<0.0001). Charlson score >=2 and older
age group were less likely to undergo surgery (p<0.0001). Median LOS was five
days (inter-quartile range [IQR] 3-7), while 30-day readmission and 30-day
mortality were 5.3% and 3.3%, respectively. Undergoing CN (hazard ratio [HR]
0.48; 95% CI 0.44-0.52; p<0.0001) and treatment at academic centres (HR 0.88; 95%
CI 0.81-0.95; p=0.001) were independently associated with improved OS. Limitation
includes retrospective design with possible selection bias. CONCLUSIONS:
Increased CN use continues in the modern era, with relatively low surgical
morbidity. Further study is required to determine if the finding of lower all
cause mortality in patients treated at academic centres is due to improved care
or unmeasured confounders.
PMID- 28503233
TI - Single penile incision for combined hypospadias and inguinal surgery: A
comparative study.
AB - INTRODUCTION: We sought to compare the surgical outcomes of hypospadias repair
with correction of inguinal pathology using a single penile incision vs.
conventional approach using two incisions. METHODS: This is a retrospective study
that reviewed all patients who underwent concurrent surgical repair for both
hypospadias and inguinal pathologies between January 2003 and November 2015.
Patients were classified into Group A, conventional (inguinal or scrotal and
penile incision) approach; or Group B, single penile incision approach. Baseline
characteristics, including age, degree of hypospadias, type and laterality of
inguinal pathology, operative time, and surgical outcomes, were collected.
Between groups, variable comparisons were analyzed using Mann-Whitney U-Test and
Fisher-exact test. Statistical significant set at <0.05. RESULTS: Seventy-six
patients (Group A: 40; Group B: 36) were eligible for study. Baseline
characteristics of both groups were comparable, with no significant statistical
difference. Overall mean operative time for Group A was 139.3 +/- 56.2 minutes,
while Group B was 107.8 +/- 46.7 minutes (Z=2.6; U=470.5; p=0.009). Two patients
in Group A and two patients in Group B had testicular ascension, all of which
also had hypospadias-related complications (p=1.0). Hypospadias-related
complications in Group A included seven urethrocutaneous fistulae and two repair
dehiscence. Eight urethrocutaneous fistulae, one urethral stricture, and two
repair dehiscence occurred in Group B (p=0.448). Surgical outcome appearance in
both groups were comparable, with no statistically significant difference
(p=0.466). CONCLUSIONS: Single penile incision for both hypospadias repair and
correction of inguinal pathology is a feasible technique and comparable to the
conventional approach, with similar surgical outcomes and shorter overall
operative time.
PMID- 28503234
TI - Error reporting from the da Vinci surgical system in robotic surgery: A Canadian
multispecialty experience at a single academic centre.
AB - INTRODUCTION: The goal of the study is to evaluate and report on the third
generation da Vinci surgical (Si) system malfunctions. METHODS: A total of 1228
robotic surgeries were performed between January 2012 and December 2015 at our
academic centre. All cases were performed by using a single, dual console, four
arm, da Vinci Si robot system. The three specialties included urology,
gynecology, and thoracic surgery. Studied outcomes included the robotic surgical
error types, immediate consequences, and operative side effects. Error rate trend
with time was also examined. RESULTS: Overall robotic malfunctions were
documented on the da Vinci Si systems event log in 4.97% (61/1228) of the cases.
The most common error was related to pressure sensors in the robotic arms
indicating out of limit output. This recoverable fault was noted in 2.04%
(25/1228) of cases. Other errors included unrecoverable electronic communication
related in 1.06% (13/1228) of cases, failed encoder error in 0.57% (7/1228),
illuminator-related in 0.33% (4/1228), faulty switch in 0.24% (3/1228), battery
related failures in 0.24% (3/1228), and software/hardware error in 0.08% (1/1228)
of cases. Surgical delay was reported only in one patient. No conversion to
either open or laparoscopic occurred secondary to robotic malfunctions. In 2015,
the incidence of robotic error rose to 1.71% (21/1228) from 0.81% (10/1228) in
2014. CONCLUSIONS: Robotic malfunction is not infrequent in the current era of
robotic surgery in various surgical subspecialties, but rarely consequential.
Their seldom occurrence does not seem to affect patient safety or surgical
outcome.
PMID- 28503235
TI - Cautery artifact understages urothelial cancer at initial transurethral resection
of large bladder tumours.
AB - INTRODUCTION: We sought to determine how frequently cautery (thermal) artifact
precludes an accurate determination of stage at initial transurethral resection
of bladder tumour (TURBT) of large bladder tumours. METHODS: We queried our
institution's billing data to identify patients who underwent TURBT for large
bladder tumours >5cm (CPT 52240) by two urologists at an academic centre from
January 2009 through April 2013. Only patients who underwent initial-staging
TURBT for urothelial cancer were included. Pathological reports were reviewed for
stage, number of separate pathological specimens per TURBT, and presence of
cautery artifact. Operative reports were reviewed for whether additional cold cup
biopsies were taken of other suspicious areas of the bladder, resident
involvement, and type of electrocautery. RESULTS: We identified 119 patients who
underwent initial staging TURBT for large tumours. Cautery artifact interfered
with accurate staging in 7/119 (6%) of cases. Of these, six patients underwent
restaging TURBT, with 50% percent experiencing upstaging to T2 disease. Tumour
size, tumour grade, whether additional cold cup biopsies were taken, number of
separate pathological specimens sent, and resident involvement were not
associated with cautery artifact (all p>0.05). Bipolar resection had a higher
rate of cautery artifact 5/42 (12%), compared to monopolar resection 2/77 (2.6%)
approaching significance (p=0.095). CONCLUSIONS: Cautery artifact may delay
accurate staging at initial TURBT for large tumours by understaging up to 6% of
patients.
PMID- 28503236
TI - Impact of neutrophil-to-lymphocyte ratio on effects of targeted therapy for
metastatic renal cell carcinoma patients with extrapulmonary metastasis.
AB - INTRODUCTION: The aim of our present study was to investigate the impact of the
pretreatment neutrophil-to-lymphocyte ratio (NLR) on the antitumour effects of
targeted agents in patients with metastatic renal cell carcinoma (mRCC). METHODS:
The NLRs in 283 cases of molecular targeted therapy for mRCC were measured before
starting the prescription of the molecular targeted agent. The significance of
pretreatment NLR on the site of metastatic organs and on progression-free
survival (PFS) in each case was analyzed. RESULTS: Metastases other than lung,
which is defined as "extrapulmonary metastasis," were observed in 190 cases
(67.1%). The median of pretreated NLR was 2.39 (0.49-68.7). In 97 of the 283
cases, pretreated NLR was 3.0 or higher. These cases were categorized as the high
NLR group and the rest as the low NLR group. When the cases with extrapulmonary
metastasis were investigated and classified based on their pretreated NLR, 50%
PFS in the high NLR and low NLR groups was 6.7 months and 12 months (p=0.0001),
respectively. Multivariate analysis revealed that high NLR (>3.0) was an
independent predictive factor for PFS in the cases with extrapulmonary metastasis
(hazard ratio 2.762; p<0.0001), while there was no significant difference between
PFS in the high and low NLR groups in cases with no extrapulmonary metastasis
(p=0.3457). CONCLUSIONS: Our data indicate that the predictive significance of
the NLR in mRCC cases involving targeted therapy depends on the metastatic
organs. NLR is an independent predictive factor of PFS in cases of mRCC with
extrapulmonary metastasis treated with targeted therapy.
PMID- 28503237
TI - Modified C index: Novel predictor of postoperative renal functional loss of
laparoscopic partial nephrectomy.
AB - INTRODUCTION: We aimed to develop a scoring system to quantify the distance
between the renal hilum and renal tumour, termed the modified C index (m-CI), and
to predict renal functional loss (RFL) following laparoscopic partial nephrectomy
(LPN). METHODS: The m-CI was measured by using computed tomography in 113
patients who underwent LPN between May 2003 and June 2014. The RFL following LPN
was calculated by examining the estimated glomerular filtration rate (eGFR) and
radioisotope renography one year postoperatively. The Pythagorean theorem was
used to calculate the distance from the tumour centre to the renal hilum. The
distance was divided by the tumour radius to obtain the m-CI. The correlation
between the m-CI and the postoperative RFL were evaluated using Pearson's
coefficient values. Multivariate logistic regression models were used to assess
the potential predictive factors of RFL following LPN. The correlation between
the m-CI and the operative time, ischemia time, and blood loss during LPN were
also evaluated by the unpaired t-test. RESULTS: Pearson's coefficient values
between the postoperative RFL and the m-CI and C index were 0.294 and 0.173,
respectively. In the multivariate analysis, the resected volume (p=0.031) and m
CI (p=0.036) significantly correlated with the postoperative RFL following LPN.
The operative time (p<0.001), ischemia time (p=0.028), and blood loss (p=0.047)
during LPN was significantly longer and larger, respectively, in the group with
shorter m-CI (<=4.5) than in the group with the longer m-CI (>4.5). CONCLUSIONS:
The present study demonstrates that the m-CI can predict RFL following LPN, as
well as the surgical difficulty.
PMID- 28503238
TI - Epidemiology of prostate and kidney cancer in the Aboriginal population of
Canada: A systematic review.
AB - INTRODUCTION: Prostate and kidney cancer rates in the Aboriginal population of
Canada is a growing issue. METHODS: A systematic review of prostate and kidney
cancer epidemiology in the Aboriginal population of Canada was performed with
international comparison and evaluation of present epidemiological disparities.
PubMed, Medline, and Embase (from January 1946 to June 2016), relevant government
published reports, and the websites of organizations contributing to prostate or
kidney cancer guidelines were searched. We included studies that informed any of
the three epidemiological questions this review is focused on answering. RESULTS:
Two systematic reviews, two meta-analyses, five literature reviews, and 21 single
study papers were included. The incidence and mortality rates of kidney cancer
were elevated among Canadian Aboriginals when compared to the provincial or
national population and to several international regions. No studies reported
data on survival. Prostate cancer incidence, mortality, and survival rates were
lower in Aboriginals provincially, nationally, and internationally, with
incidence and survival reaching statistical significance. Elevated rate of risk
factors for kidney cancer was a significant finding among Canadian Aboriginals.
Aboriginals were screened for prostate cancer less than the general Canadian
population, a trend also observed in the U.S. CONCLUSIONS: The elevated incidence
and mortality of kidney cancer among Canadian Aboriginals is most likely
attributable to the rise in lifestyle-based risk factors. Two correlations
concerning prostate cancer are made. However, due to temporal and regional
disparities in data, further investigation is required to elucidate these
observations.
PMID- 28503229
TI - CUA guideline on adult overactive bladder.
PMID- 28503239
TI - A case of renal cell carcinoma in a patient with situs inversus: Operative
considerations and a review of the literature.
AB - Situs inversus, an uncommon mirror-image reversal of the major visceral and
thoracic organs, is seldom of medical significance. However, the recognition of
their unique anatomy is extremely important for those requiring surgical
intervention. There are very few reported cases of renal cell carcinoma (RCC)
developing in people with situs inversus. To our knowledge, this is the first
reported case in Canada. A review of the literature only identified nine
published cases worldwide. Here, we review and summarize pertinent information,
including patient age and sex, size and location of tumour, method of surgery,
and pathology. Our case, a 65-year-old male, presented with left flank pain and
gross hematuria. He was diagnosed with left renal cancer as well as tumour
thrombus extending into the left renal veins and inferior vena cava (IVC),
clinical T3aN0M0. An abdomen and pelvis computed tomography (CT) scan showed a
left-to-right reversal of his organs, a mirror-image, and situs inversus was
diagnosed. A left radical nephrectomy with left renal vein and IVC tumour
thrombectomy through a left open midline incision was performed.
PMID- 28503240
TI - Response of renal cell carcinoma to ibrutinib, a bruton tyrosine kinase
inhibitor, in a patient treated for chronic lymphocytic leukemia.
PMID- 28503241
TI - Recurrent, bilateral, and metastatic pheochromocytoma in a young patient with
Beckwith-Wiedemann syndrome: A genetic link?
PMID- 28503243
TI - Appendix: Executive summary of CUA guideline on adult overactive bladder.
PMID- 28503242
TI - Surgical excision of perineal nodular induration: A cyclist's third testicle.
AB - Perineal nodular induration (PNI), or biker's nodule, is a rare, bothersome,
pseudotumour. Herein, we describe the surgical technique used to treat a healthy
cyclist who developed an enlarging PNI for five years that grew into a perineal
mass. The mass prevented him from cycling due to worsening discomfort and
heaviness. The PNI-associated mass was successfully removed by wide surgical
excision and a local advancement flap. Subsequently, the patient resumed cycling.
Histopathology report demonstrated a benign lesion with abundant ropy collagen
with native smooth muscle, vessels, and rare fibroblast-like spindle cells. With
the increasing popularity of cycling, PNI may become more common, and health
providers should be aware of this rare entity and how it can be safely removed.
PMID- 28503245
TI - Maximizing particle concentration in deterministic lateral displacement arrays.
AB - We present an improvement to deterministic lateral displacement arrays, which
allows higher particle concentration enhancement. We correct and extend previous
equations to a mirror-symmetric boundary. This approach allows particles to be
concentrated into a central channel, no wider than the surrounding gaps, thereby
maximizing the particle enrichment. The resulting flow patterns were, for the
first time, experimentally measured. The performance of the device with hard
micro-spheres and cells was investigated. The observed flow patterns show
important differences from our model and from an ideal pattern. The 18 MUm gap
device showed 11-fold enrichment of 7 MUm particles and nearly perfect enrichment
of more than 50-fold-for 10 MUm particles and Jurkat cells. This work shows a
clear path to achieve higher-than-ever particle concentration enhancement in a
deterministic microfluidic separation system.
PMID- 28503244
TI - The Intergenerational Circumstances of Household Food Insecurity and Adversity.
AB - Household food insecurity is linked with exposure to violence and adversity
throughout the life course, suggesting its transfer across generations. Using
grounded theory, we analyzed semistructured interviews with 31 mothers reporting
household food insecurity where participants described major life events and
social relationships. Through the lens of multigenerational interactions, 4
themes emerged: (1) hunger and violence across the generations, (2) disclosure to
family and friends, (3) depression and problems with emotional management, and
(4) breaking out of intergenerational patterns. After describing these themes and
how they relate to reports of food insecurity, we identify opportunities for
social services and policy intervention.
PMID- 28503246
TI - Particle concentrating and sorting under a rotating electric field by direct
optical-liquid heating in a microfluidics chip.
AB - We demonstrate a functional rotating electrothermal technique for rapidly
concentrating and sorting a large number of particles on a microchip by the
combination of particle dielectrophoresis (DEP) and inward rotating
electrothermal (RET) flows. Different kinds of particles can be attracted
(positive DEP) to or repelled (negative DEP) from electrode edges, and then the n
DEP responsive particles are further concentrated in the heated region by RET
flows. The RET flows arise from the spatial inhomogeneous electric properties of
fluid caused by direct infrared laser (1470 nm) heating of solution in a rotating
electric field. The direction of the RET flows is radially inward to the heated
region with a co-field (the same as the rotating electric field) rotation.
Moreover, the velocity of the RET flows is proportional to the laser power and
the square of the electric field strength. The RET flows are significant over a
frequency range from 200 kHz to 5 MHz. The RET flows are generated by the
simultaneous application of the infrared laser and the rotating electric field.
Therefore, the location of particle concentrating can be controlled within the
rotating electric field depending on the position of the laser spot. This multi
field technique can be operated in salt solutions and at higher frequency without
external flow pressure, and thus it can avoid electrokinetic phenomena at low
frequency to improve the manipulation accuracy for lab-on-chip applications.
PMID- 28503247
TI - Reconfigurable microfluidic device with discretized sidewall.
AB - Various microfluidic features, such as traps, have been used to manipulate flows,
cells, and other particles within microfluidic systems. However, these features
often become undesirable in subsequent steps requiring different fluidic
configurations. To meet the changing needs of various microfluidic
configurations, we developed a reconfigurable microfluidic channel with movable
sidewalls using mechanically discretized sidewalls of laterally aligned
rectangular pins. The user can deform the channel sidewall at any time after
fabrication by sliding the pins. We confirmed that the flow resistance of the
straight microchannel could be reversibly adjusted in the range of 101-105 Pa
s/MUl by manually displacing one of the pins comprising the microchannel
sidewall. The reconfigurable microchannel also made it possible to manipulate
flows and cells by creating a segmented patterned culture of COS-7 cells and a
coculture of human umbilical vein endothelial cells (HUVECs) and human lung
fibroblasts (hLFs) inside the microchannel. The reconfigurable microfluidic
device successfully maintained a culture of COS-7 cells in a log phase throughout
the entire period of 216 h. Furthermore, we performed a migration assay of
cocultured HUVEC and hLF spheroids within one microchannel and observed their
migration toward each other.
PMID- 28503248
TI - Stable microfluidic flow focusing using hydrostatics.
AB - We present a simple technique to generate stable hydrodynamically focused flows
by driving the flow with hydrostatic pressure from liquid columns connected to
the inlets of a microfluidic device. Importantly, we compare the focused flows
generated by hydrostatic pressure and classical syringe pump driven flows and
find that the stability of the hydrostatic pressure driven technique is
significantly better than the stability achieved via syringe pumps, providing
fluctuation-free focused flows that are suitable for sensitive microfluidic flow
cytometry applications. We show that the degree of flow focusing with the
hydrostatic method can be accurately controlled by the simple tuning of the
liquid column heights. We anticipate that this approach to stable flow focusing
will find many applications in microfluidic cytometry technologies.
PMID- 28503249
TI - Hierarchical Models for Multiple, Rare Outcomes Using Massive Observational
Healthcare Databases.
AB - Clinical trials often lack power to identify rare adverse drug events (ADEs) and
therefore cannot address the threat rare ADEs pose, motivating the need for new
ADE detection techniques. Emerging national patient claims and electronic health
record databases have inspired post-approval early detection methods like the
Bayesian self-controlled case series (BSCCS) regression model. Existing BSCCS
models do not account for multiple outcomes, where pathology may be shared across
different ADEs. We integrate a pathology hierarchy into the BSCCS model by
developing a novel informative hierarchical prior linking outcome-specific
effects. Considering shared pathology drastically increases the dimensionality of
the already massive models in this field. We develop an efficient method for
coping with the dimensionality expansion by reducing the hierarchical model to a
form amenable to existing tools. Through a synthetic study we demonstrate
decreased bias in risk estimates for drugs when using conditions with different
true risk and unequal prevalence. We also examine observational data from the
MarketScan Lab Results dataset, exposing the bias that results from aggregating
outcomes, as previously employed to estimate risk trends of warfarin and
dabigatran for intracranial hemorrhage and gastrointestinal bleeding. We further
investigate the limits of our approach by using extremely rare conditions. This
research demonstrates that analyzing multiple outcomes simultaneously is feasible
at scale and beneficial.
PMID- 28503251
TI - On convex least squares estimation when the truth is linear.
AB - We prove that the convex least squares estimator (LSE) attains a n-1/2 pointwise
rate of convergence in any region where the truth is linear. In addition, the
asymptotic distribution can be characterized by a modified invelope process.
Analogous results hold when one uses the derivative of the convex LSE to perform
derivative estimation. These asymptotic results facilitate a new consistent
testing procedure on the linearity against a convex alternative. Moreover, we
show that the convex LSE adapts to the optimal rate at the boundary points of the
region where the truth is linear, up to a log-log factor. These conclusions are
valid in the context of both density estimation and regression function
estimation.
PMID- 28503250
TI - Localizing Sources of Brain Disease Progression with Network Diffusion Model.
AB - Pinpointing the sources of dementia is crucial to the effective treatment of
neurodegenerative diseases. In this paper, we propose a diffusion model with
impulsive sources over the brain connectivity network to model the progression of
brain atrophy. To reliably estimate the atrophy sources, we impose sparse
regularization on the source distribution and solve the inverse problem with an
efficient gradient descent method. We localize the possible origins of
Alzheimer's disease (AD) based on a large set of repeated magnetic resonance
imaging (MRI) scans in Alzheimer's Disease Neuroimaging Initiative (ADNI)
database. The distribution of the sources averaged over the sample population is
evaluated. We find that the dementia sources have different concentrations in the
brain lobes for AD patients and mild cognitive impairment (MCI) subjects,
indicating possible switch of the dementia driving mechanism. Moreover, we
demonstrate that we can effectively predict changes of brain atrophy patterns
with the proposed model. Our work could help understand the dynamics and origin
of dementia, as well as monitor the progression of the diseases in an early
stage.
PMID- 28503252
TI - New Insights into Sequential Infiltration Synthesis.
AB - Sequential infiltration synthesis (SIS) is a process derived from ALD in which a
polymer is infused with inorganic material using sequential, self-limiting
exposures to gaseous precursors. SIS can be used in lithography to harden polymer
resists rendering them more robust towards subsequent etching, and this permits
deeper and higher-resolution patterning of substrates such as silicon. Herein we
describe recent investigations of a model system: Al2O3 SIS using trimethyl
aluminum (TMA) and H2O within the diblock copolymer, poly(styrene-block-methyl
methacrylate) (PS-b-PMMA). Combining in-situ Fourier transform infrared
absorption spectroscopy, quartz-crystal microbalance, and synchrotron grazing
incidence small angle X-ray scattering with high resolution scanning transmission
electron microscope tomography, we elucidate important details of the SIS
process: 1) TMA adsorption in PMMA occurs through a weakly-bound intermediate; 2)
the SIS kinetics are diffusion-limited, with desorption 10* slower than
adsorption; 3) dynamic structural changes occur during the individual precursor
exposures. These findings have important implications for applications such as
SIS lithography.
PMID- 28503253
TI - Research Progress on Signaling Pathway-Associated Oxidative Stress in Endothelial
Cells.
AB - Studying the mechanisms of oxidative stress in endothelial cells is vital to the
discovery of novel drugs for the treatment of cardiovascular disease. This
article reviews the progress within the field of the role of oxidative responses
in the physiology and growth of endothelial cells and emphasizes the effects of
several main signal pathways involved in the oxidative stress of endothelial
cells. Herein, we aim to provide scientific direction that can serve as a basis
for researchers specializing in the signaling pathway of oxidative stress.
PMID- 28503255
TI - The Biochemical Cascades of the Human Pancreatic beta-Cells: The Role of
MicroRNAs.
AB - Diabetes mellitus is a disease that poses a burden to the health care system due
to its prevalence and chronic nature. Understanding beta cell pathophysiology may
lead to future therapeutic options for diabetes mellitus type 1 and 2. MicroRNAs
(MiR) fine-tune beta cell biochemical cascades through specific protein targets.
This review argues that miRs may play a critical role in human islet beta cell
biology and are potential candidates for a new pharmacological strategy. We have
reviewed and presented how miRs fine tune four biochemical cascades in islet beta
cells: glucose stimulated insulin secretion, beta cell replication, apoptosis,
and development. Only studies that examine human pancreatic islets either in
vitro or in vivo are included. The unveiling role of miR pathways in regulating
human islet beta cell biology could open the door for diagnostic and therapeutic
methods for diabetes mellitus prevention and therapy.
PMID- 28503254
TI - Management of Potential Long-Term Toxicities in Breast Cancer Patients.
AB - Breast cancer is the most common non-cutaneous malignancy among women, and there
are over 3 million breast cancer survivors living in the United States today.
Excellent cure rates with modern therapies are associated with substantial
toxicities for many women; it is important that health care providers attend to
the resulting symptoms and issues to optimize quality of life in this population.
In this article, we review management options for potential long term toxicities
in breast cancer survivors, with a particular focus on bone health, fertility
preservation, premature menopause, cardiac dysfunction, and cognitive impairment.
PMID- 28503256
TI - Socialization of Culture and Coping with Discrimination Among American Indian
Families: Examining Cultural Correlates of Youth Outcomes.
AB - OBJECTIVE: The current study examines the interrelations between observed
parental cultural socialization and socialization of coping with discrimination,
and youth outcomes among a sample of 92 American Indian adolescents and their
parents in a rural reservation. METHOD: Path analysis is used to examine the
relationships among observed parental socialization (cultural socialization and
socialization of coping with discrimination), and youth-reported perceived
discrimination, ethnic identity and depression. RESULTS: Findings reveal that
higher levels of observed parental cultural socialization and socialization of
coping with discrimination predict lower levels of depression as reported by
youth 1 year later. Path analyses also show that observed parental cultural
socialization and socialization of coping with discrimination are positively
associated with youth ethnic identity. CONCLUSIONS: These findings point to the
importance of integrating familial socialization of culture and coping with
discrimination in fostering resilience among American Indian youth.
PMID- 28503257
TI - Trends with neoadjuvant radiotherapy and clinical staging for those with rectal
malignancies.
AB - AIM: To see how patterns of care changed over time, and how institution type
effected these decisions. METHODS: A retrospective analysis was performed using
the National Cancer Database, looking at all patients that were diagnosed with
rectal cancer from 1998 to 2011. We tested differences in rates of treatment and
stage migration using chi2 tests and logistic regression models. RESULTS: A
review of ninety thousand five hundred and ninety four subjects underwent
multimodality therapy for cancer of the rectum. Staging and response to treatment
varied greatly between centers. Forty-six percent of the time staging was missing
in academic practices, vs fifty-four percent of the time in community centers (P
< 0.001). As a result, twenty-percent were down-staged and eight percent up
staged in academia, whereas only fifteen percent were down-staged and 8% up
staged in community practices (P < 0.001). Forty-two percent of individuals
underwent radiation before surgery in 1998. Within two years this increased to
fifty-three percent. This increased to eighty-six percent by 2011 (P < 0.001).
Institution specific treatment varied greatly. Fifty-one percent received therapy
before surgery in academic centers in 1998. Thirty-nine percent followed this
pattern in the same year in the community (P < 0.001). By 2011, ninety-one
percent received radiation before their procedure in academic centers, vs eighty
four percent in the community (P < 0.001). Rates of adoption were better in
academia, although an increase was seen in both center types. CONCLUSION: From
the study dates of 1998 to 2011, preoperative treatment with radiation has been
on the rise. There is certainly an increased rate of use of radiation in
academia, however, this trend is also seen in the community. Practice patterns
have evolved over time, although rates of assigning clinical stage are grossly
underreported prior to initiation of preoperative therapy.
PMID- 28503258
TI - Feasibility of pancreatectomy following high-dose proton therapy for unresectable
pancreatic cancer.
AB - AIM: To review surgical outcomes for patients undergoing pancreatectomy after
proton therapy with concomitant capecitabine for initially unresectable
pancreatic adenocarcinoma. METHODS: From April 2010 to September 2013, 15
patients with initially unresectable pancreatic cancer were treated with proton
therapy with concomitant capecitabine at 1000 mg orally twice daily. All patients
received 59.40 Gy (RBE) to the gross disease and 1 patient received 50.40 Gy
(RBE) to high-risk nodal targets. There were no treatment interruptions and no
chemotherapy dose reductions. Six patients achieved a radiographic response
sufficient to justify surgical exploration, of whom 1 was identified as having
intraperitoneal dissemination at the time of surgery and the planned
pancreatectomy was aborted. Five patients underwent resection. Procedures
included: Laparoscopic standard pancreaticoduodenectomy (n = 3), open pyloris
sparing pancreaticoduodenectomy (n = 1), and open distal pancreatectomy with
irreversible electroporation (IRE) of a pancreatic head mass (n = 1). RESULTS:
The median patient age was 60 years (range, 51-67). The median duration of
surgery was 419 min (range, 290-484), with a median estimated blood loss of 850
cm3 (range, 300-2000), median ICU stay of 1 d (range, 0-2), and median hospital
stay of 10 d (range, 5-14). Three patients were re-admitted to a hospital within
30 d after discharge for wound infection (n = 1), delayed gastric emptying (n =
1), and ischemic gastritis (n = 1). Two patients underwent R0 resections and
demonstrated minimal residual disease in the final pathology specimen. One
patient, after negative pancreatic head biopsies, underwent IRE followed by
distal pancreatectomy with no tumor seen in the specimen. Two patients underwent
R2 resections. Only 1 patient demonstrated ultimate local progression at the
primary site. Median survival for the 5 resected patients was 24 mo (range, 10
30). CONCLUSION: Pancreatic resection for patients with initially unresectable
cancers is feasible after high-dose [59.4 Gy (RBE)] proton radiotherapy with a
high rate of local control, acceptable surgical morbidity, and a median survival
of 24 mo.
PMID- 28503259
TI - Five-year outcomes of laparoscopic sleeve gastrectomy as a primary procedure for
morbid obesity: A prospective study.
AB - AIM: To prospectively evaluate the postoperative morbi-mortality and weight loss
evolution of patients who underwent a laparoscopic sleeve gastrectomy (LSG) as a
primary bariatric procedure during 5 years of follow-up. METHODS: Since 2006,
data from patients undergoing a highly restrictive primary LSG have been
prospectively registered in a database and analysed. Preoperative co-morbid
conditions, operating time, hospital stay, early and late complications rate and
evolution of weight loss after 5 years of follow-up were analysed. RESULTS: A
total of 156 patients were included, 74.3% of whom were women. The mean age was
43.2 +/- 13.1 years and the mean body mass index (BMI) was 41.5 +/- 7.9 kg/m2.
Seventy patients (44.8%) presented a BMI under 40 kg/m2. The mortality rate was
0%. The leakage rate was 1.2%, and the total 30-d morbidity rate was 5.1%
(8/156). With a mean follow-up of 32.7 +/- 28.5 (range 6-112) mo, the mean
percent of excess of weight loss (%EWL) was 82.0 +/- 18.8 at 1 year, 76.7 +/-
21.3 at 3 years and 60.3 +/- 28.9 at 5 years. The mean percent of excess of BMI
loss (%EBMIL) was 94.9 +/- 22.4 at 1 year, 89.4 +/- 27.4 at 3 years and 74.8 +/-
29.4 at 5 years. Patients with preoperative BMI less than 40 kg/m2 achieved
greater weight loss than did the overall study population. Diabetes remitted in
75% of the patients and HTA improved in 71.7%. CPAP masks were withdrawn in all
patients with obstructive sleep apnoea. CONCLUSION: LSG built with a narrow 34 F
bougie and starting 3 cm from the pylorus proved to be safe and highly effective
in terms of weight loss as a stand-alone procedure, particularly in patients with
a preoperative BMI lower than 40 kg/m2.
PMID- 28503260
TI - Dynamics of Hexavalent Chromium in Four Types of Aquaculture Ponds and Its
Effects on the Morphology and Behavior of Cultured Clarias gariepinus (Burchell
1822).
AB - Hexavalent chromium is a bio accumulative toxic metal in water and fish. It
enters aquaculture ponds mainly through anthropogenic sources. Hexavalent
chromium concentrations and its effects on the morphology and behavior of Clarias
gariepinus were investigated from four aquaculture ponds for 12 weeks. Chromium
was measured using diphenyl carbohdrazide method; alkalinity and hardness were
measured using colometric method and analyzed with Bench Photometer. Temperature
and pH were measured using pH/EC/TDS/Temp combined tester. Temporal and spatial
replications of samples were done with triplicates morphological and behavioural
effects of the metal on fish were observed visually. Chromium ranged from no
detection to 0.05 mg/L, alkalinity 105 to 245 mg/L, hardness 80 to 165 mg/L, pH
6.35 to 8.03 and temperature 29.1 to 35.9 degrees C. Trend in the chromium
concentrations in the ponds is natural > earthen > concrete > collapsible. There
was a significant difference (P < 0.05) in chromium, alkalinity, water hardness,
pH and temperature among the four ponds. Significant positive correlation also
existed between alkalinity, water hardness, pH, with chromium. Morphological and
behavioural changes observed in the fish include irregular swimming, frequent
coming to the surface, dark body colouration, mucous secretion on the body,
erosion of gill epithelium, fin disintegration, abdominal distension and
lethargy. High chromium concentration in natural pond was due to anthropogenic
run-off of materials in to the pond. Acidic pH, low alkalinity, low water
hardness also contributed to the high chromium concentration. Morphological and
behavioural changes observed were attributed to the high concentrations, toxicity
and bio accumulative effect of the metal. Toxicity of chromium to fish in
aquaculture could threaten food security. Watershed best management practices and
remediation could be adopted to reduce the effects of toxicity of chromium on
pond water quality, fish flesh quality and fish welfare.
PMID- 28503261
TI - Anti-Photoaging Effects of Angelica acutiloba Root Ethanol Extract in Human
Dermal Fibroblasts.
AB - The effects that ultraviolet rays elicit on collagen synthesis and degradation
are the most common causes of wrinkle formation and photo-aging in skin. The
objectives of this study were to evaluate the effects of Angelica acutiloba root
ethanol extract (AAEE) to promote collagen synthesis and inhibit collagen
degradation in human dermal fibroblasts. By examining total polyphenol and
flavonoid contents, electron donating ability, radical scavenging activity, and
superoxide dismutase-like activity, we found that AAEE exhibited fairly good
antioxidant activity. Treatment with AAEE significantly increased type I
procollagen production by cultured fibroblasts, as well as reduced ultraviolet
induced matrix metalloproteinase-1 (MMP-1) expression and MMP-2 activity in a
dose-dependent manner (p < 0.05). In addition, AAEE significantly increased TIMP
1 mRNA expression (p < 0.05), although without an associated dose-dependent
increase in TIMP-1 protein expression. In summary, we suggest that AAEE may be a
potentially effective agent for the prevention or alleviation of skin-wrinkle
formation induced by ultraviolet rays.
PMID- 28503262
TI - Detection of Toxic Heavy Metal, Co(II) Trace via Voltammetry with Semiconductor
Microelectrodes.
AB - The cobalt (Co(II)) ion is a main component of alloys and considered to be
carcinogenic, especially due to the carcinogenic and toxicological effects in the
aquatic environment. The toxic trace of the Co(II) detection was conducted using
the infrared photodiode electrode (IPDE) using a working electrode, via the
cyclic and square-wave anodic stripping voltammetry. The results indicated a
sensitive oxidation peak current of Co(II) on the IPDE. Under the optimal
conditions, the common-type glassy carbon, the metal platinum, the carbon paste,
and the carbon fiber microelectrode were compared with the IPDE in the
electrolyte using the standard Co(II). The IPDE was found to be far superior to
the others.
PMID- 28503263
TI - Spontaneous Peripheral Ameloblastic Odontoma in a Male Sprague-Dawley Rat.
AB - Peripheral ameloblastic odontoma is a rare variant of odontogenic tumor occurring
in the extraosseous region. The present report describes a spontaneous tumor in
male Sprague-Dawley (SD) rats. The clinically confirmed nodule in the right
mandibular region was first observed when the rat was 42 weeks and remained until
the terminal sacrifice date when the animal was 48 weeks of age. At necropsy, a
well demarcated nodule, approximately 2.5 * 2.0 * 2.0 cm, protruded from the
ventral area of the right mandible. The nodule was not attached to mandibular
bone and was not continuous with the normal teeth. Histopathologically, the tumor
was characterized by the simultaneous occurrence of an ameloblastomatous
component and composite odontoma-like elements within the same tumor. The
epithelial portion formed islands or cords resembling the follicle or plexiform
pattern typical of ameloblastoma and was surrounded by mesenchymal tissue.
Formation of eosinophilic and basophilic hard tissue matrix (dentin and enamel)
resembling odontoma was observed in the center of the tumor. Mitotic figures were
rare, and areas of cystic degeneration were present. Immunohistochemically, the
epithelial component was positive for cytokeratin AE1/AE3 (CK AE1/AE3), and the
mesenchymal component and odontoblast-like cells were positive for vimentin, in
the same manner as in normal teeth. On the basis of these findings, the tumor was
diagnosed as a peripheral ameloblastic odontoma in an extraosseous mandibular
region in a SD rat. In the present study, we report the uncommon spontaneous
peripheral ameloblastic odontoma in the SD rat. We also discuss here the
morphological characteristics, origin, histochemical, and immunohistochemical
features for the diagnosis of this tumor.
PMID- 28503264
TI - Skin Wound Healing Effects and Action Mechanism of Acai Berry Water Extracts.
AB - The purpose of this study was to investigate the wound healing effect of acai
berry water extracts (ABWE) and a possible underlying mechanism involved in its
action using various in vitro and in vivo models. The wound healing effect of
ABWE was evaluated by migration assay using HS68 fibroblast cells. In addition,
its effect on mRNA expression of procollagen, fibronectin, and MMP-1 was
determined. Moreover, the wound healing effect of ABWE was evaluated in in vivo
wound models through macroscopic and microscopic observation. In addition, mRNA
expression levels of wound related genes were determined. Results revealed that
ABWE was not cytotoxic. It increased migration of HS68 fibroblast cells. ABWE
increased mRNA expression levels of fibronectin but decreased the mRNA expression
levels of MMP-1. ABWE also showed significantly potent wound healing effect in
vivo based on macroscopic and histopathological observation and mRNA expression
evaluation for wound related genes. Taken together, our results indicated that
ABWE might have potential as a wound healing agent.
PMID- 28503265
TI - The Effects of Caffeine on the Long Bones and Testes in Immature and Young Adult
Rats.
AB - This study was to evaluate the age-dependent effects of caffeine exposure on the
long bones and reproductive organs using male rats. A total of 15 immature male
rats and 15 young adult male rats were allocated randomly to three groups: a
control group and two groups fed caffeine with 120 and 180 mg/kg/day for 4 weeks.
Exposure to caffeine at either dose significantly reduced body weight gain; a
proportional reduction in muscle and fat mass in immature animals, whereas a
selective reduction in fat mass with relatively preserved muscle mass in young
adult animals. The long bones of immature rats exposed to caffeine were
significantly shorter and lighter than those of control animals along with
decreased bone minerals. However, there was no difference in the length or weight
of the long bones in young adult rats exposed to caffeine. Exposure to caffeine
reduced the size and absolute weight of the testes significantly in immature
animals in comparison to control animals, but not in young adult animals exposed
to caffeine. In contrast, the adrenal glands were significantly heavier in
caffeine-fed young adult rats in comparison to control animals, but not in
caffeine-fed immature rats. Our results clearly show that the negative effects of
caffeine on the long bones and testes in rats are different according to the age
of the rat at the time of exposure, and might therefore be caused by changes to
organ sensitivity and metabolic rate at different developmental stages. Although
the long bones and testes are more susceptible to caffeine during puberty,
caffeine has negative effects on body fat, bone minerals and the adrenal glands
when exposure occurs during young adulthood. There is a need, therefore, to
educate the public the potential dangers of caffeine consumption during puberty
and young adulthood.
PMID- 28503267
TI - Consultation - Not the time for shortcuts.
PMID- 28503266
TI - Inhalation Toxicity of Bisphenol A and Its Effect on Estrous Cycle, Spatial
Learning, and Memory in Rats upon Whole-Body Exposure.
AB - Bisphenol A (BPA) is a monomer used in a polymerization reaction in the
production of polycarbonate plastics. It has been used in many consumer products,
including plastics, polyvinyl chloride, food packaging, dental sealants, and
thermal receipts. However, there is little information available on the
inhalation toxicity of BPA. Therefore, the aim of this study was to determine its
inhalation toxicity and effects on the estrous cycle, spatial learning, and
memory. Sprague-Dawley rats were exposed to 0, 10, 30, and 90 mg/m3 BPA, 6
hr/day, 5 days/week for 8 weeks via whole-body inhalation. Mortality, clinical
signs, body weight, hematology, serum chemistry, estrous cycle parameters,
performance in the Morris water maze test, and organ weights, as well as gross
and histopathological findings, were compared between the control and BPA
exposure groups. Statistically significant changes were observed in serum
chemistry and organ weights upon exposure to BPA. However, there was no BPA
related toxic effect on the body weight, food consumption, hematology, serum
chemistry, organ weights, estrous cycle, performance in the Morris water maze
test, or gross or histopathological lesions in any male or female rats in the BPA
exposure groups. In conclusion, the results of this study suggested that the no
observable adverse effect level (NOAEL) for BPA in rats is above 90 mg/m3/6
hr/day, 5 days/week upon 8-week exposure. Furthermore, BPA did not affect the
estrous cycle, spatial learning, or memory in rats.
PMID- 28503268
TI - The roles of men in family planning - a study of married men at the UKM primary
care clinic.
AB - INTRODUCTION: Traditionally, family planning initiatives were concentrated on
women despite it being a family matter. As family dynamics evolved over the
years, fathers' involvement in family planning has become crucial in enhancing
the family well-being. OBJECTIVES: This study aimed to identify the role played
by men in family planning activities and the association of socio-economic
characteristics with these roles. METHODOLOGY: This was a cross-sectional study
carried out in a university primary care clinic. All married male attendees to
the clinic, aged 50 years and below, were approached to answer a set of self
administered questionnaires, asking for their involvement in family planning
practices. The data were analysed using descriptive and inferential statistics.
RESULTS: There were 167 participants in the study. A high proportion of men
participated in the discussions regarding previous pregnancies (60.42%), future
child planning (89.76%) and desired family size (89.76%). However, the
discussions on the usage of family planning methods (FPMs; 39.16%) were
significantly low. Socio-economic factors associated with higher likelihood of
men discussing family planning activities were older age (p < 0.0), higher
education level (p = 0.010), higher monthly income (p < 0.001) and longer
duration of marriage (p = 0.0049). CONCLUSIONS: The level of participation of men
varied in the discussions of four family planning activities. The roles taken by
men in family planning were associated with older age and higher socio-economic
class. The majority of men needs to be encouraged to play a more active role in
the discussion of FPMs.
PMID- 28503269
TI - An assessment of patient waiting and consultation time in a primary healthcare
clinic.
AB - Waiting is a common phenomenon in the doctor's waiting room. The purpose of this
audit is to assess patient waiting time and doctor consultation time in a primary
healthcare clinic and to formulate strategies for improvement. This audit was
conducted at a primary care clinic for 4 weeks using the universal sampling
method. All patients who attended the clinic during this period was included in
the study except for those who required more time to be seen such as those who
were critically ill, aggressive or those who came for repeat medication or
procedures only without needing to see the doctor. The time of arrival was
captured using the queue management system (QMS) and then the patient was given a
timing chit which had to be manually filled by the staff at every station. The
waiting time for registration, pre-consultation, consultation, appointment,
payment and pharmacy were recorded as well as consultation time. The data were
entered into the statistical software SPSS version 17 for analysis. version 17.
Results showed that more than half of the patients were registered within 15
minutes (53%) and the average total waiting time from registration to seeing a
doctor was 41 minutes. Ninety-nine percentage of patients waited less than 30
minutes to get their medication. The average consultation time was 18.21 minutes.
The problems identified in this audit were addressed and strategies formulated to
improve the waiting and consultation time were carried out including increasing
the number of staff at the registration counter, enforcing the staggered
appointment system for follow-up patients and improving the queuing system for
walk-in patients.
PMID- 28503270
TI - Early management of head injury in adults in primary care.
AB - Head injury is common and preventable. Assessment of the head injury patient
includes airway, cervical spine protection, breathing, circulation, haemorrhage
control and the Glasgow Coma Scale. Hypotension, hypoxia, hypocarbia and
hypercarbia should be avoided by continuous monitoring of vital signs and hourly
head chart to prevent secondary brain injury. This paper aims to assist primary
healthcare providers to select the appropriate patient for transfer and imaging
for further management of head injury.
PMID- 28503271
TI - Pulled/nursemaid's elbow.
AB - Nursemaid's elbow is a radial head subluxation caused by axial traction on the
extended arm while the forearm is pronated, allowing for slippage of the radial
head. A 2-year-old boy presented with pain, swelling and reduced range of
movement of the right elbow for 4 days. The mother noted that the child was
moving the right upper limb less often and there was tenderness over the right
elbow. X-ray of the right elbow showed subluxation of the elbow joint with no
obvious fracture. A trial of conservative management was decided upon and the
patient was placed on a right elbow backslab with the right forearm in a supine
position. On follow-up, there was no swelling, tenderness or neurological deficit
noted. A repeate x-ray revealed normal findings.
PMID- 28503272
TI - Von Hippel - Lindau disease.
AB - Von Hippel-Lindau (VHL) disease is a rare autosomal dominantly inherited
multisystem disorder characterised by the development of a variety of benign and
malignant tumours. We report a case of VHL disease that was inherited by a
daughter from her father, who both presented at a young age with progressive
headache and were found to have a posterior fossa haemangioblastoma (HB) on
magnetic resonance imaging (MRI). Multiple benign pancreatic and renal cysts were
also noted in both patients.
PMID- 28503273
TI - Bilateral optic neuritis with maculopathy: A rare manifestation of dengue fever.
AB - Dengue fever is a common mosquito-borne disease, which is endemic in tropical and
subtropical countries. Bilateral optic neuropathy is a relatively unusual dengue
related ocular complication. Here, we present a case of bilateral optic neuritis
with maculopathy complicating dengue infection.
PMID- 28503274
TI - Is it as dangerous as it looks?
AB - A common bony protrusion that occurs over the hard palate is sometimes mistaken
for a malignancy especially when it is large. This bony growth is a torus
palatinus (TP), which is a benign bony prominence over the hard palate. It occurs
most commonly in bilateral multiple form, and is often located at the canine to
premolar area. A basic knowledge of the assessment and management of TP is
important, particularly for the first-line family physician to ensure that the
correct information is given to the patient.
PMID- 28503275
TI - An elderly man with an air-fluid level in the middle ear.
AB - A 68-year-old Malay man who is a rubber tapper, presented with a large painful
right-sided neck swelling for 6 months, which was gradually increasing in size
and associated with odynophagia, dysphagia, hoarseness and significant weight
loss. He did not complain of any ear symptoms, but on further questioning, he
admitted having a 3-week history of occasional tinnitus and reduced hearing on
the right ear. Other ear symptoms were negative.
PMID- 28503276
TI - Do statins adversely affect the HbA1c of diabetic patients?
AB - This paper discusses the adverse effect of statins on the HbA1c levels of
diabetic patients. Studies have shown that statins may slightly worsen the HbA1c
level. The effects vary depending on the type of statins, the dosage and the
duration of therapy. However, it has been confirmed that statin use has benefits
that outweigh its harms. Therefore, a diabetic patient should be given advice on
the need for appropriate lifestyle changes and the importance of continuing the
statins.
PMID- 28503277
TI - Prevalence of diabetes, impaired fasting glucose and impaired glucose tolerance
in patients with thalassemia major in Iran: A meta-analysis study.
AB - BACKGROUND: This study aimed to investigate the prevalence of diabetes, impaired
fasting glucose (IFG) and impaired glucose tolerance (IGT) in Iranian patients
with thalassemia major. METHODS: The current study has been conducted based on
PRISMA guideline. To obtain the documents, Persian and English scientific
databases such as Magiran, Iranmedex, SID, Medlib, IranDoc, Scopus, PubMed,
ScienceDirect, Cochrane, Web of Science, Springer, Wiley Online Library as well
as Google Scholar were searched until December 2015. All steps of the study were
conducted by two authors independently. To the high heterogeneity of the studies,
the random effect model was used to combine studies. Data were analyzed using
STATA Version 11.1 software. RESULTS: Thirty-two studies involving 3959 major
thalassemia patients with mean age of 16.83 years were included in the meta
analysis. The prevalence of diabetes in Iranian patients with thalassemia major
was estimated as 9% (95% CI: 6.8-10.5) and estimated rate was 12.6% (95% CI: 6.1
19.1) for males and 10.8% (95% CI: 8.2-14.5) for females. The prevalence of IFG
and IGT were 12.9% (95% CI: 7-18.8) and 9.6% (95% CI: 6.6-12.5) respectively. No
relationship between serum ferritin and development of diabetes was noted.
CONCLUSION: The prevalence of diabetes, IFG, and IGT in patients with thalassemia
major in Iran is high and accordingly requires new management strategies and
policies to minimize endocrine disorders in Iranian patients with thalassemia
major. Screening of patients for the early diagnosis of endocrine disorders
particularly diabetes, IFG, and IGT is recommended.
PMID- 28503278
TI - Conjugate and 23-valent pneumococcal polysaccharide booster vaccination in
asplenic patients with thalassemia major: A randomized clinical trial study.
AB - BACKGROUND: Pneumococcal vaccine provides protection against invasive
pneumococcal disease in population at risk. This study was conducted to compare
the antibody response to 13-valent pneumococcal conjugate vaccine and 23-valent
pneumococcal polysaccharide vaccine in patients with thalassemia major. METHODS:
A randomized cross-over clinical trial was performed on 50 asplenic patients with
thalassemia major who referred to thalassemia center at Bouali Sina Hospital,
Sari, Iran from 2013 to 2014. Patients were divided into two equal groups. The
first group received 13-valent pneumococcal conjugate vaccine (PCV) injected into
the deltoid muscle at first and received 23-valent polysaccharide vaccine (PPV)
by the same way two months later. The second group received PPV vaccine at first
and PCV13 two months later. Levels of serum antibody were checked and measured by
enzyme-linked immunosorbent assay (ELISA) before vaccination, and then 8 weeks
after the first injection and 2 months after the second injection in all
patients. Each time 0.5-ml dose of the vaccine was injected. RESULTS: Of the 50
patients, three cases were excluded due to lack of cooperation and avoidance of
vaccination. From 47 patient participants, 28 (59.6%) were males and 19 (40.4%)
were females with age ranged between 20 to 44 years (average age of 29.6+/-1.4
years). Pneumococcal IgG levels in a group that used PCV before PPV (Group A)
increased from 114.5+/-87.7 to 1049+/-720 U/ml (p=0.0001) and in another group
that used PPV before PCV (Group B) increased from 115+/-182.2 to 1497.3+/-920.3
U/ml (P=0.0001). CONCLUSION: It can be concluded that PCV vaccine before PPV can
be more effective in asplenic thalassemia major patients as a booster dose.
PMID- 28503279
TI - Incidence and risk factors for cytomegalovirus in kidney transplant patients in
Babol, northern Iran.
AB - BACKGROUND: Cytomegalovirus (CMV) disease is an important cause of death and
possibly transplant rejection in kidney transplant (KT) patients. This study was
conducted to investigate the incidence and risk factors of CMV disease in kidney
transplant patients. METHODS: All end-stage renal disease (ESRD) patients who
underwent kidney transplantation during 1998-2014 and their donors were assessed.
All samples were followed-up for approximately 70 months. CMV was identified by
polymerase chain reaction (PCR) and/or PP65 antigen in peripheral blood
leukocytes along with clinical manifestations. RESULTS: A total of 1450 cases
participated in the current study. CMV was diagnosed in 178 out of 725 (24.6%)
kidney recipients. The annual incidence of CMV disease was 4.2%. Patients older
than 40 years had a higher incidence of CMV disease. The level of CMV disease
incidence in the 41-60 age group was 4 fold compared to those under 20 of age
group (P=0.001). CONCLUSION: This study demonstrated that the incidence of CMV
disease in our region is relatively low and also age more than 40 years and EBV
infection are the important risk factors in kidney transplant patients. So care
and monitoring of these patients are crucial in the first 5 months.
PMID- 28503280
TI - Etiological approach of chylothorax in Babol, northern Iran.
AB - BACKGROUND: Chylothorax results from leakage of lymph in the pleural cavity
because of thoracic duct injury which is associated with severe metabolic
disorders. The aim of this study was to evaluate the rate of chylothorax and its
causes among hospitalized patients in Shahid Beheshti Hospital of Babol city,
North of Iran. METHODS: In this cross-sectional study, all patients with
chylothorax admitted to the surgery department of Shahid Beheshti Hospital during
2002-2015 were included. Information including gender, age, duration of symptoms,
laboratory findings, causes of disease and the type of treatment were extracted
from the patients' records. RESULTS: Of the 42 patients, 27 (64.3%) were men and
15 (35.7%) were women. The mean age of the study population was 51.03+/-16.95.
The most common clinical symptoms were dyspnea (66.7%) and dyspnea with cough
(21.4%), respectively. In all patients, the pleural fluid triglyceride level was
greater than 110 mg/dl, whereas the presence of lymphatic in pleural fluid was
eventful in 18 (42.8%) patients. The causes of the disease were traumatic
(54.8%), non-traumatic (38.1%) and unknown (7.1%), which were not significantly
correlated with gender. Nineteen (45.2%) patients were operated, 16 (38.1%)
patients received supportive therapy, and 7 (16.7%) patients had the treatment of
the underlying conditions and then supportive therapy. CONCLUSION: According to
the results, trauma was the most common cause of chylothorax. Therefore,
identification and control of the traumatic factors seem to be the steps to
prevent and reduce the chylothorax incidence and its complications.
PMID- 28503281
TI - Effect of SeptimebTM as a new natural extract on severe sepsis: A randomized
clinical trial.
AB - BACKGROUND: Septimeb as a herbal medicine has regulatory effects on inflammation.
This study set to evaluate the effects of Septimeb among patients with sepsis on
inflammatory biomarkers and survival rate. METHODS: In this randomized clinical
trial, 51 patients with sepsis from the ICU and medical ward of Imam Khomeini
Hospital were divided into two groups: Septimeb (n=25) and control group (n=26).
In the control group, the patients received a standard treatment only for 7 days,
while Septimeb group received Septimeb (6cc vial with 500cc serum glucose
infusion 5% daily for one to two hours) plus standard treatment of sepsis for 7
days. Then, blood samples were analyzed. APACHE (Acute Physiologic and Chronic
Health Evaluation), SOFA (Sequential Organ Failure Assessment), and GCS (Glasgow
Coma Score) values were calculated daily. RESULTS: Treatment with Septimeb showed
a significant decrease in SOFA value (1.54+/-0.83) compared to the control group
(2.39+/-0.88) (P<0.001) and a significant increase in GCS value (14.46+/-0.88)
compared to the control group (12.86+/-1.78) (P<0.001). Improvements of these
values can confirm the potential of Septimeb in the reduction of severity of
sepsis (P<0.05). There were significant decreases in lactate and blood sugar and
WBC levels. In addition, inflammatory factors such as ESR (Septimeb group:
52.07+/-34.80, control group: 51.75+/-42.10, P=0.98) and CRP (Septimeb group:
48.86+/-23.21, control group: 49.93+/-36.22, P=0.92) decreased, but did not show
a significant reduction. CONCLUSION: Septimeb has positive effects on reduction
of the severity of sepsis which leads to reduction of patients' mortality rates.
PMID- 28503282
TI - Skeletal complications of brucellosis: A study of 464 cases in Babol, Iran.
AB - BACKGROUND: Skeletal complication of brucellosis is common in endemic region of
brucellosis, but its frequency has not been clearly determined. The aim of this
study was to determine the frequency of skeletal complication in brucellosis
patients in Babol, north of Iran. METHODS: From 2005-2015, 1252 cases of
brucellosis were diagnosed at the Department of Infectious Diseases, Ayatollah
Rouhani Teaching Hospital, in Babol, North of Iran. The diagnosis of brucellosis
was established using serum agglutination test (SAT>=1/160), and 2
mercaptoethanol (2ME>= 1/80) with clinical and epidemiological findings
compatible with brucellosis. Among them, 464 (37.1%) cases demonstrated skeletal
complication. The diagnosis of skeletal involvement was established with
appropriate diagnostic facilities. The data were collected and analyzed. RESULTS:
The mean age of these patients (299 males, 165 females) was 33.2+/-17.6 years.
Three hundred-thirty four (72%) cases were from rural areas. In 350 (75.4%)
patients with peripheral arthritis, 242 (52.1%) cases were monoarthritis.
Furthermore the knee arthritis was seen in 148 (31.9%) patients and hip in 54
(11.6) cases. Sacroiliitis was seen in 59 (12.7%) patients and spondylitis in 55
(11.9%) cases. There were no significant differences regarding the occurrence of
these focal lesions in both sexes. CONCLUSION: The results show that about one
third of brucellosis in human is associated with skeletal complication.
Peripheral arthritis, sacroiliitis and spondylitis are the frequent skeletal
complications of human brucellosis.
PMID- 28503283
TI - Cryptogenic hepatitis simulating cyst rupture and hydatid jaundice in a patient
with preexisting asymptomatic hydatid cyst.
AB - BACKGROUND: Rupture into the biliary ducts is the most frequent complication of
hydatid liver disease. In endemic areas of Echinococcus granulosus, development
of jaundice in a patient with liver cyst is initially suspected to have hydatid
cyst. CASE PRESENTATION: A 48 year-old woman with history of asymptomatic hydatid
liver cysts was admitted to the emergency department with right upper quadrant
abdominal pain, increased levels of liver enzymes, bilirubin and alkaline
phosphatase and the initial clinical diagnosis was the hydatid cyst rupture into
the bile ducts. Surgery was planned but radiological evaluation (MRI) revealed
non-dilated intra-extra biliary ducts. High suspicion of hydatid rupture required
diagnostic ERCP that was normal and surgery was cancelled then. A possible
diagnosis of coexistent hepatitis was suspected. Liver function tests normalized
gradually and no cyst rupture was determined during surgery. CONCLUSION: These
findings suggest considering the possible development of cryptogenic hepatitis in
patients with preexisting hydatid cyst.
PMID- 28503284
TI - Arteriovenous malformations of the colon: A report of two cases and review of the
literature.
AB - BACKGROUND: Arteriovenous malformations are one of the most common vascular
disorders of the colon. Vascular disorders present as painless, high-volume
rectal bleeding. CASE PRESENTATION: This study elucidates two rare cases of
vascular disorders that are diagnosed as angiodysplasia of the left colon and
cavernous hemangioma of the colon and rectum. The chief complaint in two patients
was rectorrhagia. The patients who were diagnosed of ulcerative colitis were
treated with sulfadiazine and prednisone. Due to continuous bleeding, the
patients were referred to the surgery department for operation. The patients
underwent total proctocolectomy. CONCLUSION: We discuss the faults in the
diagnosis and management of vascular disorders of the intestine.
PMID- 28503285
TI - Oral contraceptive-related transverse sinus thrombosis as an initial
manifestation of antiphospholipid syndrome in the absence of systemic lupus
erythematosus.
AB - BACKGROUND: Cerebral venous sinus thrombosis is a rare and potentially life
threatening neurologic manifestation of antiphospholipid syndrome. Oral
contraceptive pills (OCP) may increase the risk of vascular events, even in
people without family history of venous thrombosis. CASE PRESENTATION: A 31-year
old woman with four weeks of constant headache and history of taking OCP for one
year has been selected for this study. The results of magnetic resonance imaging
(MRI) of brain and venography confirmed a diagnosis of cerebral venous sinus
thrombosis. The serum anticardiolipin and antiphospholipid antibodies were
elevated and a definitive diagnosis of antiphospholipid syndrome was made.
CONCLUSION: The present report demonstrates the importance of screening for
antiphospholipid antibodies in patients presenting with cerebral venous sinus
thrombosis despite history of taking OCP.
PMID- 28503286
TI - Fulminant hepatic failure due to metastatic choroidal melanoma.
AB - BACKGROUND: Acute liver failure (ALF) as a consequence of metastatic disease is
extremely uncommon. The liver is the most commonly affected organ by metastatic
disease, but only a few cases of ALF in the setting of metastatic choroidal
melanoma have been reported. CASE PRESENTATION: We describe the case of a 47-year
old man with right upper quadrant pain, progressive jaundice, and unintentional
weight loss. He also reported that he had experienced reduced left visual acuity
which progressed to blindness over 2 months. On physical examination, we found a
pigmented scleral lesion in the left eye. He had a coagulopathy and, during his
hospital stay, he also developed encephalopathy. The diagnosis of ALF was
therefore established and was later attributed to metastatic uveal melanoma. In
addition, we briefly review the relevant literature. CONCLUSION: Liver metastasis
should be kept in mind when assessing abnormal liver function tests in patients
with uveal malignant melanoma.
PMID- 28503287
TI - Time to appreciate Avicenna's knowledge of rabies.
PMID- 28503288
TI - Geographical mortality distribution of cardiovascular diseases: First report from
South Khorasan, Iran.
PMID- 28503289
TI - The Three-Portal Technique in Arthroscopic Lateral Epicondylitis Release.
AB - Lateral epicondylitis, commonly referred to as tennis elbow, is a syndrome
characterized by pain over the origin of the common extensor muscles of the
fingers, hand and wrist at the lateral epicondyle. Reports of 70-90% response to
conservative treatment at one year have been documented in the literature though
refractory cases often require surgical management. Arthroscopic treatment of
lateral epicondylitis allows for intra-articular visualization for concomitant
pathology and localization of the Extensor Carpi Radialis Brevis tendon.
Additionally, compared to the open technique, the arthroscopic technique has a
lower morbidity and an earlier return to work and activity. Here we describe a
three portal technique for improved visualization in arthroscopic lateral
epicondylitis release.
PMID- 28503290
TI - Use of the Suprapatellar Approach in Intramedullary Nailing of a Multi
Fragmentary Dislocated Tibia Fracture with a Hypermobile Intermediate Fragment in
a Young Patient.
AB - A case of an adolescent female patient who suffered from first grade open multi
fragment fracture of the tibia (AO42-C2) with a large hypermobile intermediate
fragment is presented in this case report. Intramedullary nailing of the tibia
remains the treatment of choice despite a high risk of malformation and anterior
knee pain especially in multi-fragment fractures. Here the suprapatellar approach
as a semiextended nailing technique seems favorable. The specialty in our case
was an early change of procedures necessary due to persistent swelling during
external fixation based on the hypermobile intermediate fragment. Decision in
favor of this surgical technique was conducted in order to achieve beneficial
alignment and union while protecting the soft-tissue despite the hypermobile
intermediate fragment and decrease the risk of anterior knee pain. In our case we
achieved successful alignment and proper bone healing without any signs of
anterior knee pain or limitations in the range of motion of the knee. With this
report we would like to recommend the suprapatellar approach as a favorable
alternative in intramedullary nailing in this type of fracture also in young
patients.
PMID- 28503291
TI - How many more? Sample size determination in studies of morphological integration
and evolvability.
AB - 1. The variational properties of living organisms are an important component of
current evolutionary theory. As a consequence, researchers working on the field
of multivariate evolution have increasingly used integration and evolvability
statistics as a way of capturing the potentially complex patterns of trait
association and their effects over evolutionary trajectories. Little attention
has been paid, however, to the cascading effects that inaccurate estimates of
trait covariance have on these widely used evolutionary statistics. 2. Here, we
analyze the relationship between sampling effort and inaccuracy in evolvability
and integration statistics calculated from 10-trait matrices with varying
patterns of covariation and magnitudes of integration. We then extrapolate our
initial approach to different numbers of traits and different magnitudes of
integration and estimate general equations relating the inaccuracy of the
statistics of interest to sampling effort. We validate our equations using a
dataset of cranial traits, and use them to make sample size recommendations. 3.
Our results suggest that highly inaccurate estimates of evolvability and
integration statistics resulting from small sample sizes are likely common in the
literature, given the sampling effort necessary to properly estimate them. We
also show that patterns of covariation have no effect on the sampling properties
of these statistics, but overall magnitudes of integration interact with sample
size and lead to varying degrees of bias, imprecision, and inaccuracy. 4.
Finally, we provide R functions that can be used to calculate recommended sample
sizes or to simply estimate the level of inaccuracy that should be expected in
these statistics, given a sampling design.
PMID- 28503292
TI - Historical influence on the practice of chiropractic radiology: Part I - a survey
of Diplomates of the American Chiropractic College of Radiology.
AB - BACKGROUND: It is known that not all chiropractors follow mainstream guidelines
on the use of diagnostic ionising radiation. Various reasons have been discussed
in the literature, including using radiography to screen for congenital
anomalies, to perform postural analysis, to search for contraindications to
spinal manipulation, and to document chiropractic subluxations, i.e., tiny
anatomical displacements of vertebrae thought to affect nerves and health. The
visualisation of subluxations was the reason chiropractic first adopted the x-ray
in 1910. There has never been a study of the influence of this historical
paradigm of radiography on the practices of chiropractic radiologists (DACBRs or
Diplomates of the American Chiropractic College of Radiology). METHODS: A survey
was administered with a modified Dillman method using SurveyMonkey and
supplemented by hard copies distributed at a professional conference. The target
population was all active DACBRs. There were 34 items, which consisted of
multiple choice and open-ended interrogatives on all three areas in which
chiropractic radiologists work: education, clinical practice, and radiology
practice. RESULTS: The response rate was 38% (73 of 190 DACBRs). Respondents
reported that the historical paradigm of radiography was found in all areas of
practice, but not as a major aspect. The majority of respondents did not condone
that historical paradigm, but many tolerated it, particularly from referring
chiropractors. Radiographic subluxation analysis was reportedly perpetuated by
private clinical practitioners as well as technique instructors and supervising
clinicians in the teaching institutions. CONCLUSIONS: Within the chiropractic
profession, there is a continuing belief in radiographically visible subluxations
as a cause of suboptimal health. This situation is sustained in part due to the
reticence of other chiropractors to report these practices to licensing and
registration boards. Investigation into other structures supporting a vitalistic
belief system over science in chiropractic is recommended. In addition, it may be
useful to explore remunerative systems that move beyond the inherently conflicted
fee-for-service model.
PMID- 28503293
TI - Historical influence on the practice of chiropractic radiology: part II -
thematic analysis on the opinions of diplomates of the American Chiropractic
College of Radiology about the future.
AB - BACKGROUND: Over the past 20 years, various authors have addressed the question
of the future of chiropractic. Most were positive about the future, with some
advocating evidence-based practice and integration with mainstream healthcare,
some advocating continued separation with an emphasis on subluxation-based care
or the traditional/historical paradigm of chiropractic, and some calling for
tolerance and unity. No papers were found specifically inquiring about the future
of chiropractic radiology. METHODS: The study population consisted of all current
members of the American Chiropractic College of Radiology (ACCR), estimated at
190 people, known as chiropractic radiologists or Diplomates of the American
Chiropractic Board of Radiology (DACBRs). An internet-based, anonymous survey
using SurveyMonkey was implemented, supplemented by hard copies distributed at a
conference. The main point of interest for this paper is the final item of the
overall questionnaire. This item inquired about the future of chiropractic
radiology. Thematic analysis was used on the responses, coded in both
constructionist and inductive ways to extract both a general outlook and more
specific themes. The inductive themes were also assigned secondarily to a SWOT
(strengths, weaknesses, opportunities, and threats) analysis. RESULTS: The
overall response rate to the survey was 38% (73/190); within the group of
respondents, 71 of 73 (98%) answered the item that is the subject of this paper.
Opinions on the outlook for chiropractic radiology in the future were more
negative than positive, with 14 respondents giving a positive outlook, 26
negative, and 14 non-committal. 28 respondents advocated integration with the
wider healthcare community, 11 recommended emphasising separateness or a focus on
working within chiropractic, and 15 did not express an opinion on this issue. Ten
strengths were noted, 11 weaknesses, 57 opportunities, and 30 threats.
CONCLUSIONS: The increasing necessity of demonstrating evidence for diagnostic
and therapeutic procedures in healthcare makes it likely that chiropractic
radiologists and the wider chiropractic profession will need to take a more
active position on evidence-based practice. Re-evaluation of guidelines and
legislation as well as enforcement policies and practices will be necessary. The
consequences of failing to do so may include increased marginalisation and
reduced viability as a profession.
PMID- 28503295
TI - Building the infrastructure to make science metrics more scientific.
AB - Research leaders, policy makers and science strategists need evidence to support
decision-making around research funding investment, policy and strategy. In
recent years there has been a rapid expansion in the data sources available that
shed light onto aspects of research quality, excellence, use, re-use and
attention, and engagement. This is at a time when the modes and routes to share
and communicate research findings and data are also changing. In this opinion
piece, we outline a series of considerations and interventions that are needed to
ensure that research metric development is accompanied by appropriate scrutiny
and governance, to properly support the needs of research assessors and decision
makers, while securing the confidence of the research community. Key among these
are: agreed 'gold standards' around datasets and methodologies; full transparency
around the calculation and derivation of research-related indicators; and a
strategy and roadmap to take the discipline of scientific indicators and research
assessment to a more robust and sustainable place.
PMID- 28503294
TI - A survey of free-ranging deer in Ireland for serological evidence of exposure to
bovine viral diarrhoea virus, bovine herpes virus-1, bluetongue virus and
Schmallenberg virus.
AB - BACKGROUND: Deer are an important wildlife species in both the Republic of
Ireland and Northern Ireland having colonised most regions across the island of
Ireland. In comparison to cattle and sheep which represent the main farmed
ruminant species on the island, there is a lack of data concerning their
exposure, as measured by the presence of antibodies, to important viral pathogens
of ruminants. A study was therefore undertaken to investigate the seroprevalence
of wild deer to four viruses, namely bovine viral diarrhoea virus (BVDV), bovine
herpesvirus-1 (BoHV-1), Schmallenberg virus (SBV) and bluetongue virus (BTV).
RESULTS: Two panels of sera were assembled; Panel 1 comprised 259 samples (202
collected in the Republic of Ireland and 57 in Northern Ireland) between 2013 and
2015, while Panel 2 comprised 131 samples collected in the Republic of Ireland
between 2014 and 2015. Overall sika deer (Cervus nippon) were sampled most
commonly (54.8%), followed by fallow deer (Dama dama) (35.3%), with red deer
(Cervus elaphus) (4.3%) and hybrid species (0.3%) sampled less frequently, with
the species not being recorded for the remaining 5.3% of deer sampled. Age was
not recorded for 96 of the 390 deer sampled. 196 of the remainder were adults,
while 68 and 30 were yearlings and calves, respectively. Using commercially
available enzyme-linked immunosorbent assays, true prevalence and 95% confidence
intervals were calculated as 9.9%, (6.8-13.0% CI), SBV; 1.5% (0.1-3.0% CI), BoHV
1; 0.0%, 0-1.7% CI), BVDV; and 0.0%, (0.01-0.10% CI), BTV. CONCLUSIONS: The
results indicate a very low seroprevalence for both BVDV and BoHV-1 in the wild
deer tested within the study and, are consistent with a very low prevalence in
Ireland. While serological cross-reaction with cervid herpesviruses cannot be
excluded, the results in both cases suggest that the presence of these viruses in
deer is not a significant risk to their control and eradication from the cattle
population. This is important given the ongoing programme to eradicate BVDV in
Ireland and deliberations on a national eradication programme for BoHV-1. The SBV
results show consistency with those reported from cattle and sheep on the island
of Ireland, while the BTV results are consistent with this virus remaining exotic
to Ireland. The results provide a baseline against which future surveys of either
wild or farmed/captive deer populations can be compared.
PMID- 28503298
TI - Patterns of ocular inflammation in patients with miliary tuberculosis.
AB - BACKGROUND: Ocular morbidity associated with systemic tuberculosis is common. The
clinical picture varies from anterior uveitis, intermediate uveitis and posterior
uveitis to even panuveitis. There is little data on the correlation between
specific systemic presentations and the ocular inflammation. We conducted a
retrospective review of the ocular findings in the case records of patients
admitted with a diagnosis of miliary tuberculosis. These patients were then
referred for a more detailed ophthalmic evaluation. METHODS: We analysed the case
records of patients with a clinical diagnosis of miliary tuberculosis over a 10
year period at Lilavati Hospital and Research Center, Mumbai. RESULTS: In total,
11 immunocompetent patients were identified. All 22 eyes showed normal findings
on slit lamp examination. Dilated fundus examination showed single or multiple
tubercles. In our cohort, the ocular findings were exclusively in the form of
choroidal tuberculosis, either unilaterally or bilaterally. Slit lamp examination
revealed no anterior segment inflammation Conclusions: We suggest that this
pattern of choroidal/retinal tuberculosis in the absence of anterior and
intermediate segment inflammation is specific for miliary tuberculosis and may be
related to a specific immune response.
PMID- 28491280
TI - AR2, a novel automatic muscle artifact reduction software method for ictal EEG
interpretation: Validation and comparison of performance with commercially
available software.
AB - Objective: To develop a novel software method (AR2) for reducing muscle
contamination of ictal scalp electroencephalogram (EEG), and validate this method
on the basis of its performance in comparison to a commercially available
software method (AR1) to accurately depict seizure-onset location. Methods: A
blinded investigation used 23 EEG recordings of seizures from 8 patients. Each
recording was uninterpretable with digital filtering because of muscle artifact
and processed using AR1 and AR2 and reviewed by 26 EEG specialists. EEG readers
assessed seizure-onset time, lateralization, and region, and specified confidence
for each determination. The two methods were validated on the basis of the number
of readers able to render assignments, confidence, the intra-class correlation
(ICC), and agreement with other clinical findings. Results: Among the 23
seizures, two-thirds of the readers were able to delineate seizure-onset time in
10 of 23 using AR1, and 15 of 23 using AR2 (p<0.01). Fewer readers could
lateralize seizure-onset (p<0.05). The confidence measures of the assignments
were low (probable-unlikely), but increased using AR2 (p<0.05). The ICC for
identifying the time of seizure-onset was 0.15 (95% confidence interval (CI),
0.11-0.18) using AR1 and 0.26 (95% CI 0.21-0.30) using AR2. The EEG
interpretations were often consistent with behavioral, neurophysiological, and
neuro-radiological findings, with left sided assignments correct in 95.9% (CI
85.7-98.9%, n=4) of cases using AR2, and 91.9% (77.0-97.5%) (n=4) of cases using
AR1. Conclusions: EEG artifact reduction methods for localizing seizure-onset
does not result in high rates of interpretability, reader confidence, and inter
reader agreement. However, the assignments by groups of readers are often
congruent with other clinical data. Utilization of the AR2 software method may
improve the validity of ictal EEG artifact reduction.
PMID- 28503299
TI - DangerTrack: A scoring system to detect difficult-to-assess regions.
AB - Over recent years, multiple groups have shown that a large number of structural
variants, repeats, or problems with the underlying genome assembly have dramatic
effects on the mapping, calling, and overall reliability of single nucleotide
polymorphism calls. This project endeavored to develop an easy-to-use track for
looking at structural variant and repeat regions. This track, DangerTrack, can be
displayed alongside the existing Genome Reference Consortium assembly tracks to
warn clinicians and biologists when variants of interest may be incorrectly
called, of dubious quality, or on an insertion or copy number expansion. While
mapping and variant calling can be automated, it is our opinion that when these
regions are of interest to a particular clinical or research group, they warrant
a careful examination, potentially involving localized reassembly. DangerTrack is
available at https://github.com/DCGenomics/DangerTrack.
PMID- 28503297
TI - Cardiovascular involvement and manifestations of systemic Chikungunya virus
infection: A systematic review.
AB - BACKGROUND: In the last three years, chikungunya virus disease has been
spreading, affecting particularly the Americas, producing more than two million
cases. In this setting, not only new disease-related epidemiological patterns
have been found, but also new clinical findings have been reported by different
research groups. These include findings on the cardiovascular system, including
clinical, electrocardiographic and echocardiographic alterations. METHODS: We
performed a systematic review looking for reports about cardiovascular compromise
during chikungunya disease. Cardiac compromise is not so common in isolated
episodes; but countries where chikungunya virus is an epidemic should be well
informed about this condition. We used 6 bibliographical databases as resources:
Medline/Pubmed, Embase, ScienceDirect, ClinicalKey, Ovid and SciELO. Dengue
reports on cardiovascular affectation were included as well, to compare both
arbovirus' organic affectations. Articles that delved mainly into the rheumatic
articular and cutaneous complications were not considered, as they were not in
line with the purpose of this study. The type of articles included were reviews,
meta-analyses, case-controls, cohort studies, case reports and case series.
RESULTS: Originally based on 737 articles, our reviewed selected 40 articles with
54.2% at least mentioning CHIKV cardiovascular compromise within the systemic
affectation. Cardiovascular manifestations can be considered common and have been
reported in France, India, Sri Lanka, Malaysia, Colombia, Venezuela and USA,
including mainly, but no limited to: hypotension, shock and circulatory collapse,
Raynaud phenomenon, arrhythmias, murmurs, myocarditis, dilated cardiomyopathy,
congestive insufficiency, heart failure and altered function profile (Troponins,
CPK). CONCLUSIONS: Physicians should be encouraged to keep divulgating reports on
the cardiovascular involvement of chikungunya virus disease, to raise awareness
and ultimately encourage suitable diagnosis and intervention worldwide.
PMID- 28503300
TI - How to decrease bronchopulmonary dysplasia in your neonatal intensive care unit
today and "tomorrow".
AB - Bronchopulmonary dysplasia, or BPD, is the most common chronic lung disease in
infants. Genetic predisposition and developmental vulnerability secondary to
antenatal and postnatal infections, compounded with exposure to hyperoxia and
invasive mechanical ventilation to an immature lung, result in persistent
inflammation, culminating in the characteristic pulmonary phenotype of BPD of
impaired alveolarization and dysregulated vascularization. In this article, we
highlight specific areas in current management, and speculate on therapeutic
strategies that are on the horizon, that we believe will make an impact in
decreasing the incidence of BPD in your neonatal intensive care units.
PMID- 28503301
TI - Is there a role for ischaemic conditioning in cardiac surgery?
AB - Coronary artery disease (CAD) is a major cause of morbidity and mortality
worldwide. Coronary artery bypass graft (CABG) surgery is the revascularisation
strategy of choice in patients with diabetes mellitus and complex CAD. Owing to a
number of factors, including the ageing population, the increased complexity of
CAD being treated, concomitant valve and aortic surgery, and multiple
comorbidities, higher-risk patients are being operated on, the result of which is
an increased risk of sustaining perioperative myocardial injury (PMI) and poorer
clinical outcomes. As such, new treatment strategies are required to protect the
heart against PMI and improve clinical outcomes following cardiac surgery. In
this regard, the heart can be endogenously protected from PMI by subjecting the
myocardium to one or more brief cycles of ischaemia and reperfusion, a strategy
called "ischaemic conditioning". However, this requires an intervention applied
directly to the heart, which may be challenging to apply in the clinical setting.
In this regard, the strategy of remote ischaemic conditioning (RIC) may be more
attractive, as it allows the endogenous cardioprotective strategy to be applied
away from the heart to the arm or leg by simply inflating and deflating a cuff on
the upper arm or thigh to induce one or more brief cycles of ischaemia and
reperfusion (termed "limb RIC"). Although a number of small clinical studies have
demonstrated less PMI with limb RIC following cardiac surgery, three recently
published large multicentre randomised clinical trials found no beneficial
effects on short-term or long-term clinical outcomes, questioning the role of
limb RIC in the setting of cardiac surgery. In this article, we review ischaemic
conditioning as a therapeutic strategy for endogenous cardioprotection in
patients undergoing cardiac surgery and discuss the potential reasons for the
failure of limb RIC to improve clinical outcomes in this setting. Crucially, limb
RIC still has the therapeutic potential to protect the heart in other clinical
settings, such as acute myocardial infarction, and it may also protect other
organs against acute ischaemia/reperfusion injury (such as the brain, kidney, and
liver).
PMID- 28503304
TI - Clinico- pathologic presentation of hypersensitivity pneumonitis in Egyptian
patients: a multidisciplinary study.
AB - BACKGROUND: Hypersensitivity pneumonitis (HP) is a common diffuse parenchymal
lung disease in Egypt which can be difficult to recognize due to the dynamic
symptoms & associated environmental factors. METHODS: Forty-three Egyptian
patients were enrolled in this study, presenting with dyspnea and cough,
predominant ground-glass opacity (GGO) in high-resolution computed tomography
(HRCT) where lung biopsy was needed to establish the diagnosis. RESULTS: The age
range was 15 to 60 years. Females represented 90.7% (39 patients) while 9.3% (4
patients) of our patients were males. History of contact with birds was detected
in 9 (20.9%) patients. Most of our patients (60.5%) didn't have exposure history,
and only 8 patients (18.6%) were living in geographic areas in Egypt that are
known for the exposure to environmental etiologic factors (cane sugar exhaust
fumes). The most common HRCT pattern was GGO with mosaic parenchyma in 18
patients (41.86%), followed by GGO with centrilobular nodules in 9 patients
(20.93%), then isolated diffuse GGO in 5 patients (11.62%), GGO with traction
bronchiectasis in 4 patients (9.3%), GGO with consolidation in 3 patients
(6.97%), GGO with reticulations in 2 patients (4.65%), and GGO with cysts in 2
patients (4.65%). The most common histologic finding was isolated multinucleated
giant cells in 38 patients (88.3%) commonly found in airspaces (24 patients) and
less commonly in the interstitium (14 patients), followed by interstitial
pneumonia and cellular bronchiolitis in 36 patients (83.7% each), interstitial
ill-formed non-necrotizing granulomas in 12 patients (27.9%), fibrosis in 10
patients (23.2%), and organizing pneumonia pattern in 4 patients (9.3%).
CONCLUSION: The diagnosis of HP presenting with predominant GGO pattern in HRCT
requires a close interaction among clinicians, radiologists, and pathologists.
Some environmental and household factors may be underestimated as etiologic
factors. Further environmental and genetic studies are needed especially in
patients with negative exposure history.
PMID- 28503302
TI - Reliability and validity of using telephone calls for post-discharge surveillance
of surgical site infection following caesarean section at a tertiary hospital in
Tanzania.
AB - BACKGROUND: Surgical site infection (SSI) is a common post-operative complication
causing significant morbidity and mortality. Many SSI occur after discharge from
hospital. Post-discharge SSI surveillance in low and middle income countries
needs to be improved. METHODOLOGY: We conducted an observational cohort study in
Dodoma, Tanzania to examine the sensitivity and specificity of telephone calls to
detect SSI after discharge from hospital in comparison to a gold standard of
clinician review. Women undergoing caesarean section were enrolled and followed
up for 30 days. Women providing a telephone number were interviewed using a
structured questionnaire at approximately days 5, 12 and 28 post-surgery. Women
were then invited for out-patient review by a clinician blinded to the findings
of telephone interview. RESULTS: A total of 374 women were enrolled and an
overall SSI rate of 12% (n = 45) was observed. Three hundred and sixteen (84%)
women provided a telephone number, of which 202 had at least one telephone
interview followed by a clinical review within 48 h, generating a total of 484
paired observations. From the clinical reviews, 25 SSI were diagnosed, of which
telephone interview had correctly identified 18 infections; telephone calls did
not incorrectly identify SSI in any patients. The overall sensitivity and
specificity of telephone interviews as compared to clinician evaluation was 72
and 100%, respectively. CONCLUSION: The use of telephone interview as a
diagnostic tool for post-discharge surveillance of SSI had moderate sensitivity
and high specificity in Tanzania. Telephone-based detection may be a useful
method for SSI surveillance in low-income settings with high penetration of
mobile telephones.
PMID- 28503305
TI - Three Dimensional Conjugation of Recombinant N-Cadherin to a Hydrogel for In
Vitro Anisotropic Neural Growth.
AB - Living cells are extensively being studied to build functional tissues that are
useful for both fundamental and applied bioscience studies. Increasing evidence
suggests that cell-cell adhesion controlled by intercellular cadherin junction
plays important roles in the quality of the resulting engineered tissue. These
findings prompted efforts to interrogate biological effects of cadherin at a
molecular scale; however, few efforts were made to harness the effects of
cadherin on cells cultured in an in vivo-like three dimensional matrix. To this
end, this study reports a hydrogel matrix three dimensionally functionalized with
a controlled number of Fc-tagged recombinant N-cadherins (N-Cad-Fc). To retain
the desired conformation of N-Cad, these cadherins were immobilized and oriented
to the gel by anti-Fc-antibodies chemically coupled to gels. The gels were
processed to present N-Cad-Fc in uniaxially aligned microchannels or randomly
oriented micropores. Culturing cortical cells in the functionalized gels
generated a large fraction of neurons that are functional as indicated by
increased intracellular calcium ion concentrations with the microchanneled gel.
In contrast, direct N-Cad-Fc immobilization to microchannel or micropore walls of
the gel limited the growth of neurons and increased the glial to neuron ratio.
The results of this study will be highly useful to organize a wide array of
cadherin molecules in a series of biomaterials used for three-dimensional cell
culture and to regulate phenotypic activities of tissue-forming cells in an
elaborate manner.
PMID- 28503303
TI - A study on HIV, Syphilis, and Hepatitis B and C virus infections among female sex
workers in the Republic of Congo.
AB - BACKGROUND: Female Sex Workers (FSWs) are considered to be at high risk for
transmission of Sexually Transmitted Infections (STIs) and are defined as a
priority of the national HIV/AIDS response in the Republic of Congo (RoC).
However, no data are available regarding STIs in this group. This study aimed to
determine the prevalences of HIV, syphilis and hepatitis B and C among FSWs in
five cities in the country. METHODS: A cross-sectional study was conducted from
November 2nd 2011 to May 15th 2012. Participants were recruited in Brazzaville,
Pointe-Noire, Dolisie, Nkayi and Pokola using a respondent-driven sampling
method. RESULTS: A total of 805 FSWs were recruited with an average age of 28.31
+/- 9.15 years. The overall prevalences of HIV, syphilis, HBV and HCV were 7.50%,
2.20%, 4.20% and 0.70%, respectively. The age groups 35-39 (20.51% [0%-36.93%], p
= 0.0057) and greater than 40 years (16.67% [0%-34.93%], P = 0.016) were
positively associated with behaviors at high risk of HIV infection. For syphilis,
the most infected age group was the one greater than 40 years, at 6.25% ([1.06%
72.37%] p = 0.04). Pointe-Noire was the most infected city for syphilis and HBV,
with 5.15% (p = 0.0061) and 4.22% (p?0.001), respectively. No risk factors were
associated with HCV infection. FSWs practicing in mobile prostitution sites had a
significantly higher infection rate (2.1% [0%-11.09%] p = 0.04). CONCLUSION: This
study shows that the prevalence of HIV and other STIs in FSWs is high. Therefore,
a combination of individual and structural interventions could reduce the risk of
an STI "reservoir" among this population.
PMID- 28503306
TI - The drive to generate multiple forms of oncogenic cyclin D1 transcripts in mantle
cell lymphoma.
AB - Alternative polyadenylation is a rapidly emerging form of gene regulation, which
in its simplest form, enables the generation of mRNA transcripts that code for
the same protein but have 3'UTRs of different lengths and regulatory content. For
oncogenes, shorter 3'UTRs would be preferred as a mechanism to evade miRNA
regulation. The shortening of the 3'UTR of cyclin D1 in mantle cell lymphoma
offers provocative insights into this process. Patient samples have revealed that
3'UTR shortening may occur due to mutations, or translocations that result in the
generation of a chimeric 3'UTR. The truncated cyclin D1 3'UTRs resulting from
alternative polyadenylation, use a premature canonical polyadenylation signal
close to the stop codon that was generated either as a result of mutations or
provided by another gene in the chimeric 3'UTR. The sequence of the
polyadenylation signal in mantle cell lymphoma appears to be critical for 3'end
formation of the cyclin D1 transcript. Shortening the 3'UTR allows cyclin D1 to
potentially evade regulation by over 80 miRNAs that are predicted to bind to its
full length 3'UTR.
PMID- 28503307
TI - Clinical significance of intronic variants in BRAF inhibitor resistant melanomas
with altered BRAF transcript splicing.
AB - Alternate BRAF splicing is the most common mechanism of acquired resistance to
BRAF inhibitor treatment in melanoma. Recently, alternate BRAF exon 4-8 splicing
was shown to involve an intronic mutation, located 51 nucleotides upstream of
BRAF exon 9 within a predicted splicing branch point. This intronic mutation was
identified in a single cell line but has not been examined in vivo. Herein we
demonstrate that in three melanomas biopsied from patients with acquired
resistance to BRAF inhibitors, alternate BRAF exon 4-8 splicing is not associated
with this intronic branch point mutation. We also confirm that melanoma cells
expressing BRAF splicing variants retain exquisite sensitivity to existing FDA
approved MEK inhibitors.
PMID- 28503308
TI - Portal hypertension as the initial manifestation of POEMS syndrome: a case
report.
AB - BACKGROUND: Portal hypertension has a broad differential diagnosis. POEMS
syndrome is an uncommon cause of it. POEMS syndrome is a rare disease involving
multiple organs. In differential diagnosis of portal hypertension, POEMS syndrome
should be considered especially when other symptoms such as numbness,
organomegaly, endocrine alteration and skin changes also present, as it is
highlighted by our case. CASE PRESENTATION: We report a 46-year-old Chinese male,
a teacher, presenting with portal hypertension. Electromyography revealed
peripheral neuropathy. Immunofixation showed monoclonal immunoglobulin A lambda
protein. The diagnosis of POEMS syndrome was established. After treatment of
lenalidomide combined with dexamethasone over 2 years, the patient achieved a
considerable improvement. CONCLUSION: This case highlights the manifestation of
portal hypertension in POEMS syndrome. Lenalidomide with or without dexamethasone
is effective for portal hypertension due to POEMS syndrome, though esophageal and
gastric varices seems not reversible so easily.
PMID- 28503309
TI - Are there two forms of isometric muscle action? Results of the experimental study
support a distinction between a holding and a pushing isometric muscle function.
AB - BACKGROUND: In isometric muscle function, there are subjectively two different
modes of performance: one can either hold isometrically - thus resist an
impacting force - or push isometrically - therefore work against a stable
resistance. The purpose of this study is to investigate whether or not two
different isometric muscle actions - the holding vs. pushing one (HIMA vs PIMA) -
can be distinguished by objective parameters. METHODS: Ten subjects performed two
different measuring modes at 80% of MVC realized by a special pneumatic system.
During HIMA the subject had to resist the defined impacting force of the
pneumatic system in an isometric position, whereby the force of the cylinder
works in direction of elbow flexion against the subject. During PIMA the subject
worked isometrically in direction of elbow extension against a stable position of
the system. The signals of pressure, force, acceleration and mechanomyography/
tendography (MMG/MTG) of the elbow extensor (MMGtri/MTGtri) and the abdominal
muscle (MMGobl) were recorded and evaluated concerning the duration of
maintaining the force level (force endurance) and the characteristics of MMG-/MTG
signals. Statistical group differences comparing HIMA vs. PIMA were estimated
using SPSS. RESULTS: Significant differences between HIMA and PIMA were
especially apparent regarding the force endurance: During HIMA the subjects
showed a decisively shorter time of stable isometric position (19 +/- 8 s) in
comparison with PIMA (41 +/- 24 s; p = .005). In addition, during PIMA the
longest isometric plateau amounted to 59.4% of the overall duration time of
isometric measuring, during HIMA it lasted 31.6% (p = .000). The frequency of
MMG/MTG did not show significant differences. The power in the frequency ranges
of 8-15 Hz and 10-29 Hz was significantly higher in the MTGtri performing HIMA
compared to PIMA (but not for the MMGs). The amplitude of MMG/MTG did not show
any significant difference considering the whole measurement. However, looking
only at the last 10% of duration time (exhaustion), the MMGtri showed
significantly higher amplitudes during PIMA. CONCLUSION: The results suggest that
under holding isometric conditions muscles exhaust earlier. That means that there
are probably two forms of isometric muscle action. We hypothesize two potential
reasons for faster yielding during HIMA: (1) earlier metabolic fatigue of the
muscle fibers and (2) the complexity of neural control strategies.
PMID- 28503310
TI - Individual capacity-building approaches in a global pharmaceutical systems
strengthening program: a selected review.
AB - BACKGROUND: Medicines use related challenges such as inadequate adherence, high
levels of antimicrobial resistance and preventable adverse drug reactions have
underscored the need to incorporate pharmaceutical services to help achieve
desired treatment outcomes, and protect patients from inappropriate use of
medicines. This situation is further constrained by insufficient numbers of
pharmaceutical personnel and inappropriate skill mix. Studies have addressed
individual capacity building approaches of logistics, supply chain or disease
specific interventions but few have documented those involving such pharmacy
assistants/professionals, or health workers/professionals charged with improving
access and provision of pharmaceutical services. We examined how different
training modalities have been employed and adapted to meet country-specific
context and needs by a global pharmaceutical systems strengthening program in
collaboration with a country's Ministry of Health and local stakeholders.
METHODS: Structured, content analysis of training approaches from twelve selected
countries and a survey among conveniently selected trainees in Bangladesh and
Ethiopia. RESULTS: Case-based learning, practice and feedback, and repetitive
interventions such as post-training action plan, supportive supervision and
mentoring approaches are effective, evidence-based training techniques. In
Ethiopia and Bangladesh, over 94% of respondents indicated that they have
improved or developed skills or competencies as a result of the program's
training activities. Supportive supervision structures and mentorship have been
institutionalized with appropriate management structures. National authorities
have been sensitized to secure funding from domestic resources or from the global
fund grants for post-training follow-up initiatives. The Pharmaceutical
Leadership Development Program is an effective, case-based training modality that
motivates staff to develop quality-improvement interventions and solve specific
challenges. Peer-to-peer learning mechanisms than traditional didactic methods
was a preferred intervention among high level government officials both within
country and between countries. CONCLUSION: Interventions must involve local
institutions in the design and delivery of content for both pre-service and in
service training as well as web-based methods where feasible. Such efforts would
meet the changing demand in the pharmaceutical system, and promote the ownership
of the human capacity development interventions. The cost-effective partnership
with universities demonstrate that competency based pre-service training will
prepare the future pharmaceutical workforce with a critical foundation of
knowledge and skills required to meet the growing demand for patient-centered
pharmaceutical services in resource-constrained countries.
PMID- 28503311
TI - A community resource for exploring and utilizing genetic diversity in the USDA
pea single plant plus collection.
AB - Globally, pea (Pisum sativum L.) is an important temperate legume crop for food,
feed and fodder, and many breeding programs develop cultivars adapted to these
end-uses. In order to assist pea development efforts, we assembled the USDA Pea
Single Plant Plus Collection (PSPPC), which contains 431 P. sativum accessions
with morphological, geographic and taxonomic diversity. The collection was
characterized genetically in order to maximize its value for trait mapping and
genomics-assisted breeding. To that end, we used genotyping-by-sequencing-a cost
effective method for de novo single-nucleotide polymorphism (SNP) marker
discovery-to generate 66 591 high-quality SNPs. These data facilitated the
identification of accessions divergent from mainstream breeding germplasm that
could serve as sources of novel, favorable alleles. In particular, a group of
accessions from Central Asia appear nearly as diverse as a sister species, P.
fulvum, and subspecies, P. sativum subsp. elatius. PSPPC genotypes can be paired
with new and existing phenotype data for trait mapping; as proof-of-concept, we
localized Mendel's A gene controlling flower color to its known position. We also
used SNP data to define a smaller core collection of 108 accessions with similar
levels of genetic diversity as the entire PSPPC, resulting in a smaller germplasm
set for research screening and evaluation under limited resources. Taken
together, the results presented in this study along with the release of a
publicly available SNP data set comprise a valuable resource for supporting
worldwide pea genetic improvement efforts.
PMID- 28503312
TI - Germline and somatic genetic changes in multicentric tumors obtained from a
patient with multiple endocrine neoplasia type 1.
AB - Multiple endocrine neoplasia type 1 (MEN1) is a hereditary cancer syndrome caused
by germline mutations of the MEN1 gene located in chromosome 11q13. In patients
with MEN1, multicentric tumors develop in the involved organs; however, precise
evaluation of genetic changes in these multicentric tumors has not been
performed. In the present study, using whole-exome sequencing, we analyzed
germline and somatic genetic changes in blood cells, two pancreatic endocrine
tumors and one duodenal tumor obtained from a patient with MEN1 gastrinoma. We
found that this patient possessed a novel germline mutation of the MEN1 gene
[NM_137099.2:c.1505dupA (p.Lys502Lysfs); the localization was Chr11:64572134 on
Assembly GRCh37], in which an adenine insertion in codon 502 of the MEN1 gene
resulted in a frame shift and a premature stop codon. In terms of heterozygosity,
the mutated allele was heterozygous in blood cells, hemizygous in the two
pancreatic tumors and homozygous in the duodenal tumor. Immunohistochemical
staining confirmed that only truncated menin protein accumulated in the nucleus
of the tumor tissues. Further evaluation of tumor-specific somatic mutations in
two pancreatic tumors did not detect single-nucleotide variations (SNVs) in 609
cancer-associated genes designated by the COSMIC cancer gene census, suggesting
that the germline MEN1 mutation and resultant loss of heterozygosity played a
major role in tumorigenesis. In the duodenal tumor, in addition to the germline
MEN1 mutation, single-nucleotide variations in two cancer-associated genes were
found. Further studies are required to clarify the role of these somatic single
nucleotide variations in the progression of MEN1 tumors.
PMID- 28503313
TI - Novel DHCR7 mutation in a case of Smith-Lemli-Opitz syndrome showing 46,XY
disorder of sex development.
AB - Smith-Lemli-Opitz syndrome is an autosomal recessive disease caused by mutations
in 7-dehydrocholesterol reductase (DHCR7), which is rarely observed in Japan. We
report a Japanese case with 46,XY disorder of sex development and Y-shaped 2-3
toe syndactyly. DHCR7 gene analysis revealed compound heterozygous mutations
including the novel mutation H442R. Early diagnosis led to starting cholesterol
treatment at an early age.
PMID- 28503314
TI - Atypical teratoid/rhabdoid tumor of lumbar spine in a toddler child.
AB - BACKGROUND: Atypical teratoid/rhabdoid tumor (AT/RT) is a rare pediatric central
nervous system malignancy with poor outcome. AT/RT is infrequently located in the
spinal cord. CLINICAL PRESENTATION: A 16-month-old boy presented with progressive
urinary retention and weakness of the lower extremities. Magnetic resonance
imaging of the spine revealed an intradural extramedullary mass occupying the
spinal canal at the level of T10-L3. The tumor was successfully resected by using
neuroendoscopy. Histopathology demonstrated rhabdoid cells with eccentric nuclei
and eosinophilic cytoplasmic hyaline inclusions. Immunohistologically, the tumor
cells showed positive for epithelial membrane antigen, vimentin and neuron
specific enolase, and negative for integrase interactor 1. After surgery, the
patient showed significant improvement in sitting and other neurological signs
but presenting with flaccid neurogenic bladder. Intrathecal chemotherapy under
European Rhabdoid Registry (EU-RHAB) protocol with Doxorubicin, Carboplatin,
Etoposide, Ifosfamide, Vincristine, Cyclophosphamide and Actinomycin-D was given.
However, recurrent intradural extramedullary tumor at the level of T11-L2
developed in 3 months. CONCLUSION: We report a young Asian case of AT/RT in
thoracolumbar spine with recurrent tumor shortly after complete surgical
resection of the tumor.
PMID- 28503315
TI - 'Problematic methodology'.
PMID- 28503316
TI - Recovery of supraspinal control of leg movement in a chronic complete flaccid
paraplegic man after continuous low-frequency pelvic nerve stimulation and FES
assisted training.
AB - INTRODUCTION: More than 30 years ago, functional electrical stimulation (FES) was
developed as an orthotic system to be used for rehabilitation for SCI patients.
In the present case report, FES-assisted training was combined with continuous
low-frequency stimulation of the pelvic somatic nerves in a SCI patient. CASE
PRESENTATION: We report on unexpected findings in a 41-year-old man with chronic
complete flaccid paraplegia, since he was 18 years old, who underwent spinal stem
cell therapy and a laparoscopic implantation of neuroprosthesis (LION procedure)
in the pelvic lumbosacral nerves. The patient had complete flaccid sensomotoric
paraplegia T12 as a result of a motor vehicle accident in 1998. In June 2011, he
underwent a laparoscopic implantation of stimulation electrodes to the sciatic
and femoral nerves for continuous low-frequency electrical stimulation and
functional electrical stimulation of the pelvic nerves. Neither intraoperative
direct stimulation of the pelvic nerves nor postoperative stimulation induced any
sensation or muscle reactions. After 2 years of passive continuous low-frequency
stimulation, the patient developed progressive recovery of electrically assisted
voluntary motor functions below the lesions: he was first able to extend the
right knee and 6 months later, the left. He is currently capable of voluntary
weight-bearing standing and walking (with voluntary knee movements) about 50 m
with open cuff crutches and drop foot braces. DISCUSSION: Our findings suggest
that continuous low-frequency pelvic nerve stimulation in combination with FES
assisted training might induce changes that affect both the upper and the lower
motor neuron and allow supra- and infra-spinal inputs to engage residual spinal
and peripheral pathways.
PMID- 28503317
TI - Diagnostic accuracy of single channel cystometry for neurogenic bladder diagnosis
following spinal cord injury: a pilot study.
AB - INTRODUCTION: This is a cross-sectional study of 1 year duration (August 2013 to
August 2014). The objective of the study was to investigate the diagnostic
accuracy of single channel cystometry (SCC) for confirmation of neurogenic
bladder following spinal cord injury. MATERIALS AND METHODS: The study was
conducted in both out-patient and in-patient services of Department of
Rehabilitation Medicine, Hospital Sungai Buloh, Malaysia. Subjects in the study
include sixteen patients with a clinical diagnosis of neurogenic bladder
following spinal cord injury aged between 15 and 62 years. Patients with a
clinical diagnosis of neurogenic bladder were subjected to cystometric evaluation
using SCC in our hospital. Confirmation of the diagnosis was made by urodynamic
study (UDS) in another hospital. SCC procedure involved manual intra-vesical
pressure assessment using a 12F Nelaton catheter. Cystometric parameter
measurement taken in this study was detrusor pressure (cm H2O) done at regular
intervals from baseline, throughout bladder filling phase and voiding/leaking
phase. The relationship between detrusor pressure to bladder volume from initial
bladder filling until voiding or leaking phase was recorded, analyzed and graph
plotted. Maximum detrusor pressure (cm H2O) during bladder filling, voiding or
leaking and the maximum cystometric capacity (mls) was recorded. RESULTS: SCC was
found to have 100% sensitivity, 50% specificity, 93.33% positive predictive value
and 100% negative predictive value for neurogenic bladder diagnosis. Only 55.55%
patients with SCC suspicion of detrusor sphincter dyssynergia (DSD) had
comparable UDS findings. DISCUSSION: The use of SCC may be considered for
objective confirmation of neurogenic bladder diagnosis following spinal cord
lesion in centers with limited access to UDS. However, we are not able to
establish its clinical application for confirmation of DSD.
PMID- 28503318
TI - Erratum: Against the odds: extraordinary recovery from complete cauda equina
syndrome following L3 fracture. Time still matters.
AB - [This corrects the article DOI: 10.1038/scsandc.2016.27.].
PMID- 28503319
TI - An unexpected delivery: pregnancy experience of a paraplegic lady.
AB - INTRODUCTION: Spinal cord injury (SCI) has increased over the years, and so has
the survival. Women with SCI remain fertile and have equal chance of pregnancy.
CASE PRESENTATION: We described a case of a 29-year-old lady with traumatic
spinal cord injury (SCI) resultant with paraplegia in 2008, who conceived
naturally 2 years after the injury. She only had her antenatal check-up at a low
risk antenatal center throughout her pregnancy and was not referred to
specialized obstetric care. She did not appreciate active labor, and unexpectedly
had a precipituous labor and gave birth in the bathroom. DISCUSSION: Pregnancy is
relatively safe in women with spinal cord injury (SCI). However, disability
related issues can be exaggerated during pregnancy, delivery and post-partum
periods. Thus, understanding common issues related to pregnancy in this
population is important. Specialized obstetric care with rehabilitation input
throughout antenatal and postnatal care is crucial for a good overall outcome of
a pregnant woman with SCI.
PMID- 28503320
TI - Subacute posttraumatic ascending myelopathy: a literature review.
PMID- 28503321
TI - Response to comment on subacute post-traumatic ascending myelopathy: a literature
review.
PMID- 28503322
TI - Changes in oxidized LDL during a half marathon in athletes with spinal cord
injuries.
AB - INTRODUCTION: We reported previously that exercise significantly increases plasma
adrenaline and oxidized low-density lipoprotein (oxLDL) in healthy subjects but
not in persons with spinal cord injury (SCI). Since oxLDL and adrenaline levels
are associated with oxidant/antioxidant balance, and exercise training elicits
production of reactive oxygen species, we elucidated the effects of exercise on
adrenaline, oxidant/antioxidant balance and oxLDL in individuals with SCI. CASE
PRESENTATION: Eight subjects with cervical spinal cord injury (CSCI) and nine
subjects with lower lesion of SCI (lower SCI (LSCI)) participated in a wheelchair
half marathon race, and blood samples were collected before (pre), immediately
after (post) and 1 h after the race (post 1 h). The blood samples were used to
determine adrenaline, derivatives of reactive oxygen metabolites (d-ROMs) and
biological antioxidant potential (BAP), both as markers for oxidant/antioxidant
balance. DISCUSSION: Pre-serum oxLDL levels were 147.2+/-8.1 and 97.0+/-10.4 U l
1 (mean+/-s.e.m.) in LCSI and CSCI subjects, respectively, and remained stable
throughout the study. Adrenaline levels were higher in LSCI athletes than in CSCI
athletes, especially post half marathon. Serum d-ROMs level did not change
between pre and post in both groups. The mean BAP was significantly higher in
LSCI than in CSCI subjects (2574+/-94.6 vs 2118+/-94.6 MUmol l-1) at post,
whereas the oxidative stress index (d-ROMs/BAP) was similar in the two groups
throughout the study. In conclusion, exercise did not increase the d-ROMs or d
ROMs/BAP ratio in CSCI and LSCI subjects. The lack of increase in the plasma
oxLDL level in SCI subjects was not due to the lack of response of adrenaline to
exercise.
PMID- 28503323
TI - Severe cervical flexion myelopathy with long tract signs: a case report and a
review of literature.
AB - INTRODUCTION: Hirayama disease, a type of cervical flexion myelopathy, is a rare
neurological disease characterized by muscular atrophy of the forearms and hands.
Generally, the pathology is limited to the gray matter of the anterior horns in
the lower cervical spinal cord. However, in rare cases the damage can spread to
the white matter and present as long tract signs. CASE PRESENTATION: We report on
a 30-year-old female whose onset presented as unilateral muscle atrophy of the
right hand in her teens. Despite conservative treatment using a cervical collar,
she developed prolonged bilateral muscle atrophy, sensory disturbance and spastic
gait, along with bladder and rectal disturbances. Her hands were frozen into a
'claw-like' gesture and her intrinsic muscles were highly atrophic. She was
unable to unclench her hands. Although the space available for the spinal cord
was large, the spinal cord was highly atrophic. She had local kyphosis with a
large (61 degrees ) flexion range of motion. During flexion the spinal cord was
stretched, resulting in contact with the posterior wall of the vertebrae.
Posterior fusion surgery was performed to prevent progression of the myelopathy.
After surgery, she gained mild improvement in both muscle strength and her hand's
movement. However, her spastic gait and muscle atrophy remained. DISCUSSION: Most
cases of cervical flexion myelopathy as represented by Hirayama disease have a
self-limiting benign prognosis. However, some cases can develop advanced
myelopathy with long tract signs. Long-term follow-up is recommended for these
cases because they may require early surgical treatment.
PMID- 28503324
TI - A 5-day antibiotic course for treatment of intermittent catheter-associated
urinary tract infection in patients with spinal cord injury.
AB - INTRODUCTION: This was a retrospective monocentric study conducted at Centre
Calve, France, with the objective of evaluating the effectiveness of a 5-day
course of antibiotics for symptomatic (mild urinary tract infection, UTI) or
asymptomatic (aBact) bacteriuria in patients with spinal cord injury on
intermittent catheterization. CASE PRESENTATION: This study was conducted from
May 2013 to September 2016. Antibiotic selection always followed culture
collection and analysis of antibiograms. Patients with febrile UTI (>38 degrees
5) or recent history of urolithiasis were excluded. DISCUSSION: Fifty-seven
patients underwent 111 5-day courses of antibiotics. The two main bacteria
involved were Escherichia coli and Klebsiella Pneumoniae. Most commonly
prescribed antibiotics were cephalosporins, cotrimoxazole, fluoroquinolones and
nitrofurantoins. On day 4 of the antibiotic course, bacteria were eradicated in
99% of cases. Clinical cure occurred in all patients by day 5 (end of treatment).
After treatment, recurrence of UTI occurred in 16% of patients at week 3, 38% at
week 6 and 50% at week 9. This rate was not significantly different from patients
initially treated for aBact (20%, 35% and 44%, respectively). The UTI-free period
was significantly shorter after treatment for aBact (45.5 days) than after
treatment for UTI (53.7 days). None of the following characteristics were found
to be risk factors for UTI: level or severity of lesion, gender, voiding mode,
use of anticholinergic drugs and time since lesion. Results of this study support
the use of a short 5-day course of antibiotics to treat mild UTI in patients with
spinal cord injury, and provide further evidence against treatment of aBact.
PMID- 28503325
TI - Ceftolozane/tazobactam for febrile UTI due to multidrug-resistant Pseudomonas
aeruginosa in a patient with neurogenic bladder.
AB - INTRODUCTION: Urinary tract infections (UTI) are a major public health problem
among spinal cord injury (SCI) patients. They frequently involve multidrug
resistant (MDR) bacteria. Ceftolozane/tazobactam (C/T) is a novel antibiotic
combination approved for complicated intra-abdominal and UTI caused by Gram
positive and Gram-negative organisms, including some MDR strains. Little is known
about the use of this agent for complicated febrile UTI occurring among SCI
patients with neurogenic bladder due to MDR Pseudomonas aeruginosa (PSA). CASE
PRESENTATION: We describe the case of a 35-year-old man with SCI due to multiple
sclerosis, with a neurogenic bladder necessitating a bilateral nephrostomy and
double J catheter, who developed a febrile UTI due to a MDR PSA, which was
susceptible only to amikacin and colistin. Because of this MDR phenotype and the
underlying kidney disease, a 1000 mg (1000 mg per 500 mg) dose of C/T was given
as monotherapy every 8 h for 7 days, after 3 days of colistin and amikacin.
Thanks to this treatment, the patient had a favorable outcome with no clinical
signs of UTI or positive urine culture up to 1 month after diagnosis. DISCUSSION:
C/T seems to be an effective and safe therapeutic option for febrile UTI due to
MDR PSA in SCI patients with neurogenic bladder, even when administered in
monotherapy for 10 days.
PMID- 28503326
TI - Incomplete paraplegia caused by extramedullary hematopoiesis in a patient with
thalassemia intermedia.
AB - INTRODUCTION: Extramedullary hematopoiesis (EMH) is the production of blood cell
precursors outside the bone marrow that occur in various hematological diseases.
In patients with thalassemia intermedia, ineffective erythropoiesis drives
compensatory EMH in the liver, pancreas, pleura, spleen, ribs and spine. CASE
PRESENTATION: We describe a patient with thalassemia intermedia who presented
with acute neurological symptoms caused by paraspinal EMH, which responded well
to combination therapy of steroid, hypertransfusion, laminectomy and excision of
pseudotumor and hydroxyurea therapy to boost the formation of fetal haemoglobin.
DISCUSSION: Prompt recognition of EMH based on clinical presentation and typical
radiological findings should be made. Early treatment is recommended to prevent
irreversible damage to the spinal cord.
PMID- 28503327
TI - The characteristics of traumatic spinal cord injuries at a referral hospital in
Northern Tanzania.
AB - STUDY DESIGN: Retrospective study. OBJECTIVES: To describe the epidemiology of
traumatic spinal cord injury (TSCI) in Northern Tanzania. SETTING: Main referral
hospital for Northern Tanzania. METHODS: A retrospective review of 125 TSCI cases
admitted to Kilimanjaro Christian Medical Centre (KCMC) over a period of 5 years.
RESULTS: We included 125 patients in the sample size, with a male majority of 107
(85.6%), giving a male-to-female ratio of 5.9:1. The mean age at injury was 39.9
(+/-16.0) years. Overall, 66 (52.8%) were farmers and an overwhelming majority
(109 (87.2%)) were referrals from peripheral medical centres. Fall injuries
accounted for 65 (52.0%) of the admissions and 49 (39.2%) were injured due to a
Road Traffic Accident (RTA). Severity of injury was classified according to the
American Spinal Injury Association Impairment Scale (AIS) and 57 (45.6%) injuries
were categorised as AIS A and 68 (54.4%) as AIS BCD. Cervical level injuries (59
(47.2%)) were the most frequent among the cohort. The in-hospital mortality rate
was 24.1%. CONCLUSION: The majority of patients affected by TSCIs were young
males and the most common cause was fall injuries. Cervical level injuries were
the most common and in-hospital mortality was high.
PMID- 28503329
TI - Optical Fluorescence Microscopy for Spatially Characterizing Electron Transfer
across a Solid-Liquid Interface on Heterogeneous Electrodes.
AB - Heterogeneous catalytic materials and electrodes are used for (electro)chemical
transformations, including those important for energy storage and utilization.1,
2 Due to the heterogeneous nature of these materials, activity measurements with
sufficient spatial resolution are needed to obtain structure/activity
correlations across the different surface features (exposed facets, step edges,
lattice defects, grain boundaries, etc.). These measurements will help lead to an
understanding of the underlying reaction mechanisms and enable engineering of
more active materials. Because (electro)catalytic surfaces restructure with
changing environments,1 it is important to perform measurements in operando. Sub
diffraction fluorescence microscopy is well suited for these requirements because
it can operate in solution with resolution down to a few nm. We have applied sub
diffraction fluorescence microscopy to a thin cell containing an electrocatalyst
and a solution containing the redox sensitive dye p-aminophenyl fluorescein to
characterize reaction at the solid-liquid interface. Our chosen dye switches
between a nonfluorescent reduced state and a one-electron oxidized bright state,
a process that occurs at the electrode surface. This scheme is used to
investigate the activity differences on the surface of polycrystalline Pt, in
particular to differentiate reactivity at grain faces and grain boundaries.
Ultimately, this method will be extended to study other dye systems and electrode
materials.
PMID- 28503328
TI - Phrenic pacing compared with mechanical ventilation.
AB - STUDY DESIGN: Comparable case series. OBJECTIVES: High-cervical spinal cord
injury (SCI) may disrupt the ability to breathe sufficiently. To restore
respiration a phrenic nerve pacer can be implanted. The aims of this study were
to describe the use of phrenic nerve pacing in tetraplegics in Denmark and
compare the users with a population of ventilator dependent tetraplegics.
SETTING: Clinics for Spinal Cord Injuries, and Respiratory Centre East,
Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. METHODS: Nine
tetraplegic individuals who had implantation of a phrenic nerve pacer and 16 home
mechanical ventilator dependent tetraplegics met the inclusion criteria. Data
were retrieved from medical records and a structured follow-up interview with
seven individuals from each group. RESULTS: No significant differences were found
when comparing age at injury, time since injury, length of hospitalization,
incidence of pneumonia, number of pneumonia hospitalizations, number of tracheal
suctions, speech quality and activities of daily living or quality of life. On
the Short Form Health Survey (SF36) mental health summary the median for both
users of phrenic nerve pacing and users of mechanical ventilation was one s.d.
above the mean of a standard population. CONCLUSIONS: Nine people have had a
phrenic nerve pacer implanted. They do not significantly differ from a group of
home mechanical ventilator dependent tetraplegics on a number of performance
measures, but both groups seem to have better quality of life than a standard
population.
PMID- 28503330
TI - Febuxostat Attenuates Renal Damage besides Exerting Hypouricemic Effect in
Streptozotocin-Induced Diabetic Rats.
AB - Aim. In this study, we aimed to investigate the effects of febuxostat, a novel
inhibitor of xanthine oxidase (XO), on renal damage in streptozotocin- (STZ-)
induced diabetic rats. Methods. Diabetes was induced by the intraperitoneal
injection of STZ in male Sprague-Dawley rats. Sham-injected rats served as
controls. The control and diabetic rats were treated with and without febuxostat
for 8 weeks, respectively. Fasting blood and 24-h urine samples were collected
every 4 weeks. Rat livers were extracted for detecting gene expression, content,
and bioactivity of XO. Results. Diabetic rats showed significantly increased
serum uric acid (SUA), serum creatinine (SCr), and urea nitrogen (BUN) levels.
Daily urinary albumin (UAE), uric acid (UUA), and creatinine (UCr) excretion were
also significantly increased in these rats. In diabetic rats, at week 8,
febuxostat decreased SUA by 18.9%, while UAA was increased by 52.0%. However, UCr
and urinary urea nitrogen (UUN) levels remained unchanged, while SCr and BUN
levels decreased by >30% in these rats. Although hepatic gene expression,
content, and activity of XO increased significantly in diabetic rats, febuxostat
only slightly decreased its content. Conclusions. Febuxostat significantly
attenuated renal damage in STZ-induced diabetic rats in addition to exerting
hypouricemic effect.
PMID- 28503332
TI - Chronic Neuropsychological Sequelae in a Patient with Nontumorous Anti-NMDA
Receptor Encephalitis.
AB - Anti-N-methyl-D-aspartate receptor encephalitis is a neurological, autoimmune
disorder tightly conceptualized only as recently as the mid-2000s. It presents
itself in a combination of psychiatric, neurological, and autonomic features. We
observe a unique case with probable earlier episode (prior to the mid-2000s
conceptualization of the disease) and a later relapse, accompanying a
comprehensive neuropsychological profile tracked after the relapse and subsequent
improvement. Neurocognitive findings revealed residual frontal deficits with mood
changes even in the state after plasmapheresis. This case is the first to
describe posttreatment cognition in anti-NMDAR encephalitis after probable serial
autoimmune episodes.
PMID- 28503333
TI - Peritoneal Keratin Granulomatosis Associated with Endometrioid Adenocarcinoma of
the Uterine Corpus in a Woman with Polycystic Ovaries: A Potential Pitfall-A Case
Report and Review of the Literature.
AB - Peritoneal keratin granulomatosis is a rare condition included under
granulomatous lesions of the peritoneum. It can be secondary to neoplasms of the
female genital tract and can mimic carcinomatosis intraoperatively. A case of a
40-year-old woman with a history of polycystic ovaries and a chief complaint of
vaginal bleeding is presented. She was diagnosed with endometrioid adenocarcinoma
with squamous differentiation in endometrial curettings. Intraoperatively, many
peritoneal nodules were found, interpreted as peritoneal carcinomatosis. The
woman underwent a total abdominal hysterectomy with bilateral salpingo
oophorectomy, omentectomy, bilateral pelvic lymphadenectomy, and appendicectomy.
Multiple biopsies were taken, as well as peritoneal washings. Microscopic
examination revealed multiple keratin granulomas on the serosal surface of the
ovaries, fallopian tubes, appendix, and omentum. Lymph node metastasis was not
found. Peritoneal keratin granulomas (PKGs) have been reported in cases of
endometrioid adenocarcinoma with squamous differentiation of the uterine corpus,
ovary, and atypical adenomyoma. It should be noted that the prognosis of cases of
peritoneal keratin granulomas without viable tumor cells is favourable and that
the histologic examination is essential for its diagnosis. We report a case of
PKG in a patient with endometrial carcinoma with squamous differentiation, being
the first in a woman with polycystic ovaries.
PMID- 28503334
TI - Retained Surgical Drains in Orthopedics: Two Case Reports and a Review of the
Literature.
AB - Though a relatively rare event, retained surgical drains are preventable and can
lead to significant consequences. Two case reports from our institution are
discussed as examples for the challenging management of this problem as well as
an overview of techniques for the prevention and removal of retained drains based
on the current literature.
PMID- 28503331
TI - Exercise Modality Is Differentially Associated with Neurocognition in Older
Adults.
AB - This study explored the effects of exercise modality and type of fitness index on
cognitive function in the older adults as assessed via behavioral and
neuroelectrical approaches. Sixty older adults were assigned to an aerobic
exercise, a coordination exercise, or a control group based on their previous
exercise experience. The participants completed congruent and incongruent trials
of a modified Stroop Test, during which, event-related potentials were recorded.
The participants also completed multiple physical tests that assessed health- and
skill-related fitness. Our findings suggest that, in general, both aerobic and
coordination exercise, as well as higher scores on health- and skill-related
fitness indices, are positively associated with better performance of various
cognitive functions in the elderly population. The mechanisms underlying these
relationships may be differentially related to specific neuroelectrical processes
involved in neurocognitive control.
PMID- 28503335
TI - Primary Villoglandular Mucinous Adenocarcinoma of the Vulva.
AB - Primary villoglandular mucinous adenocarcinoma of the vulva is rare tumor. We
report a case of 68-year-old woman who developed this very uncommon malignant
tumor. Immunohistochemical examination of this tumor revealed positive staining
for Cytokeratin 20, Mucin 2, and CDX2, although Cytokeratin 7 and Mucin 6 were
negative. This positive staining indicated the tumor enteric type characters. In
order to exclude the possibility of the metastasis from another site, we
thoroughly evaluated clinical data and extensively investigated the whole body.
However, we could not detect any other tumors. The patient was treated by tumor
resection. The patient remains free of disease 5 years after surgery.
PMID- 28503336
TI - Plasmacytoma as a Mimicker of Colonic Carcinoma in an Elderly Man.
AB - Multiple myeloma is a neoplastic proliferation of monoclonal plasma cells.
Although it is usually restricted to the bone marrow, extraskeletal spread in the
form of localised extramedullary collections of malignant plasma cells
(plasmacytomas) can occur. However, gastrointestinal tract involvement in
multiple myeloma is rare and overt gastrointestinal bleeding from plasmacytoma is
uncommon. We report a case of colonic plasmacytoma which presented with bleeding
per rectum and was initially misdiagnosed as colonic neuroendocrine carcinoma.
Later the patient presented with recurrence of the colonic mass along with
multiple lytic bone lesions. The diagnosis of colonic plasmacytoma with
progression into multiple myeloma was given. We also discuss here the diagnostic
difficulty of plasma cell neoplasms in small biopsies of the colon.
PMID- 28503337
TI - Complete Ectopia Cordis: A Case Report and Literature Review.
AB - Ectopia cordis is a congenital heart exposure defined as complete or partial
protrusion of heart through ventral defect in the thoracoabdominal wall alone or
with other viscera in cases of pentalogy of Cantrell. This condition was first
described by Haller et al. in 1706; since then many advances have been made.
Diagnosis of ectopia cordis is done prenatally in well-equipped health facility
by antenatal ultrasound scan so that early diagnosis and management plan can be
initiated. The index case was delivered to uneducated rural family and admitted
at 3 days of life and survived for seven days, even though most literatures state
that majority died within four days even with surgery. So, in view of this, we
presented this case report to deliberately draw the attention of
paediatrician/obstetrician to the fact that even though this condition is rare,
proactive search and diagnosis should be made and early treatment should be
instituted, so that such a child may be salvaged.
PMID- 28503339
TI - Restoration and Management of Healthy Wetland Ecosystems.
PMID- 28503338
TI - Infrarenal Infected Aortic Aneurysm Caused by Streptococcus pyogenes.
AB - Infectious aneurysm is a rare entity associated with significant morbidity and
mortality. Current knowledge on pathogenesis, outcome, diagnosis, management, and
follow-up remains debatable. We report the case of a patient with Streptococcus
pyogenes aneurysm who was successfully treated with a homograft implant and
discuss microbiological characteristics, diagnostic methods, and treatment
options currently available for this serious disease.
PMID- 28503341
TI - Peripheral and Central Nervous System Involvement in Recently Diagnosed Cases of
Hypothyroidism: An Electrophysiological Study.
AB - BACKGROUND: Hypothyroidism, one of the most common endocrine disorders, may
induce neurological abnormalities at an early stage of the disease. AIM: The
study was designed to assess the electrophysiological alterations of some
selected variables of nerve conduction, brainstem auditory evoked potentials
(BAEPs), and visual evoked potentials (VEPs) in hypothyroid patients. SUBJECTS
AND METHODS: Sixty patients of newly diagnosed hypothyroidism and an equal number
of age-matched controls were selected for the study. Nerve conduction studies
that included parameters as latencies, conduction velocities, and amplitude of
motor nerves, i.e., median, ulnar, common peroneal, tibial nerve, and sensory
nerves, i.e., median and sural nerves was performed in both hypothyroid patients
and controls. Further, BAEPs and VEPs of all the patients were done. The data
were compiled and statistically analyzed using Student's unpaired t-test to
observe any electrophysiological alterations in hypothyroid patients as compared
to healthy controls. RESULTS: On comparative evaluation, statistically
significant increase in latency of median, ulnar, tibial, and sural nerves;
decrease in conduction velocities of all the tested nerves and decrease in
amplitude of median, tibial, and sural nerves was observed in hypothyroid
patients. Statistically significant increase in latencies, interpeak latencies,
and decrease in amplitudes of BAEP waves and statistically significant increase
in P100 latency of VEP was seen in hypothyroid patients. CONCLUSION: The results
of our study suggest that peripheral and central neuropathy develops in patients
of hypothyroidism at an early stage of disease and the electrophysiological
investigations of such patients can help in timely detection and treatment of
neurological disorders that occur due to thyroid hormone deficiency.
PMID- 28503340
TI - Administration frequency as well as dosage of PTH are associated with development
of cortical porosity in ovariectomized rats.
AB - To investigate whether the administration frequency of parathyroid hormone (PTH)
is associated with the development of cortical porosity, this study established
15 dosage regimens of teriparatide [human PTH(1-34), TPTD] with four distinct
concentrations and four distinct administration frequencies of TPTD to 16-week
old ovariectomized rats. Our analyses demonstrated that the bone mineral density,
mechanical properties, and bone turnover were associated with the total amount of
TPTD administered. Our observations further revealed that the cortical porosity
was markedly developed as a result of an increased administration frequency with
a lower concentration of total TPTD administration in our setting, although the
highest concentration also induced cortical porosity. Deconvolution fluorescence
tiling imaging on calcein-labeled undecalcified bone sections also demonstrated
the development of cortical porosity to be closely associated with the bone site
where periosteal bone formation took place. This site-specific cortical porosity
involved intracortical bone resorption and an increased number and proximity of
osteocytic lacunae, occasionally causing fused lacunae. Taken together, these
findings suggested the involvement of local distinctions in the rate of bone
growth that may be related to the site-specific mechanical properties in the
development of cortical porosity induced by frequent and/or high doses of TPTD.
PMID- 28503342
TI - Phenotypic Detection and Antibiogram of beta-lactamase-producing Proteus Species
in a Tertiary Care Hospital, India.
AB - BACKGROUND: Proteus species cause a variety of community- and hospital-acquired
illnesses. Synthesis of beta-lactamases is the predominant mechanism for
resistance to beta-lactam antibiotics. Among the beta-lactamases, extended
spectrum beta-lactamases (ESBLs) and AmpC beta-lactamases are the most common.
AIM: The objective of this study was to determine the occurrence of ESBL and AmpC
beta-lactamases in Proteus species among various clinical isolates at a tertiary
care hospital, India. MATERIALS AND METHODS: This study was done to identify
various species of Proteus from clinical samples (n = 3922). Antimicrobial
susceptibility was performed by Kirby-Bauer disc diffusion method. ESBL
production was detected by modified double-disc synergy test and indirect
modified three-dimensional tests and AmpC beta-lactamase production by AmpC disc
test and modified Hodge test. RESULTS: Proteus species were isolated in 5.4%
(101/1876) specimens. Three Proteus species isolated were Proteus mirabilis 62.4%
(63/101), Proteus vulgaris 29.7% (30/101), and Proteus penneri 7.9% (8/101). ESBL
producers confirmed by both tests were of 88.1% (89/101). Only AmpC beta
lactamase was produced by four isolates. Coproduction of ESBL and AmpC beta
lactamase was observed in 58.4% (52/89) of isolates. Twelve isolates were non
beta-lactamase producers. Multidrug resistance (MDR) was found in 95.1% (96/101)
of isolates, 50.5% (51/101) were possibly extensively drug resistant and none
were pan drug resistant. None of the isolates were resistant to piperacillin
tazobactam. P. penneri isolates exhibited high resistance to most of the
antibiotics. CONCLUSIONS: A high prevalence of ESBL and AmpC beta-lactamases was
found that concurrently showed MDR. Phenotypic methods for the detection of beta
lactamases are easy and simple and can be implemented in routine diagnostic
laboratories along with susceptibility testing. These data will assist the
clinicians in the management and control of infections.
PMID- 28503343
TI - Evaluation of Serum and Urinary Neopterin Levels as a Biomarker for Occupational
Exposure to Crystalline Silica.
AB - BACKGROUND: Crystalline silica is a commonly used mineral in various industries
and construction activities, and it is so important introducing potential
biomarkers to identify early indicators of biological effects in its high-risk
occupational exposures. AIM: The present study was aimed to assess the blood and
urinary neopterin as an early biomarker of exposure in the workers of an
insulator manufacturing plant who are exposed to crystalline silica. SUBJECTS AND
METHODS: This analytical descriptive study was done among two groups of exposed
workers (n = 55) and unexposed office workers (n = 38) of an insulator
manufacturing plant. Statistical software R was used to determine sample size and
select the participants by random sampling among nonsmoker workers. Sampling of
airborne silica in breathing zone of participants was done based on the National
Institute for Occupational Safety and Health method 7601. The urinary and blood
samples were collected and prepared for analysis by high-performance liquid
chromatography to determine the level of urinary and serum neopterin. All of the
statistical analyses were carried out using SPSS 22. RESULTS: The airborne silica
concentration was significantly different between two exposed and unexposed
groups (P < 0.001, 0.27 [0.11] vs. 0.0028 [0.0006] mg/m3, respectively). The
urinary neopterin in exposed group is significantly higher than the unexposed one
(P < 0.001, 97.67 [30.24] vs. 55.52 [2.18] MUmol/mol creatinine, respectively).
Neopterin level of serum in exposed group is higher than the unexposed group, and
there is a significant difference between them (P < 0.001, 6.90 [2.70] vs. 2.20
[1.20] nmol/l, respectively). The positive significant correlations were found
between silica exposure concentration with urinary and serum neopterin (P <
0.001, r = 0.36 and 0.59, respectively). CONCLUSIONS: Considering the sensitively
and easily measurement of neopterin in biological fluid and also the
statistically significant positive relationships which were found between the
airborne silica concentration and neopterin levels in the present study, the
serum and urinary neopterin levels can be considered the potential biomarkers of
silica exposure for doing further comprehensive studies in this area.
PMID- 28503344
TI - Adnexal Tumors of Skin: An Experience at a Tertiary Care Center at Delhi.
AB - BACKGROUND: Adnexal skin tumors are a heterogeneous group of uncommon tumors
usually misdiagnosed clinically due to a huge variety of types and their
variants. Histopathology usually helps in establishing the diagnosis. AIMS: The
study was undertaken to analyze the morphological, clinical, and histological
features of adnexal tumors (ATs) of the skin at our center over a period of 4
years. SUBJECTS AND METHODS: retrospective study was conducted over a period of 4
years (April 2010-March 2014), comprising 25 ATs of skin diagnosed in the
Department of Pathology, Hamdard Institute of Medical Sciences and Research,
Jamia Hamdard, New Delhi. All the consecutively reported AT cases were reviewed
and reclassified as AT arising from sebaceous glands, hair follicles, or sweat
glands. The concordance of clinical and histopathological diagnosis was also
assessed. RESULTS: Most of the ATs were benign (24/25) with head and neck being
the most common location (72%). Nearly 56% of the tumors exhibited sweat gland
differentiation, 28% hair follicle differentiation, and sebaceous gland tumors
accounted for 16%. The most common varieties of tumors encountered in the present
study included hidradenoma papilliferum and pilomatricoma. The concordance
between clinical and histopathological diagnosis was found to be 50%
approximately. CONCLUSIONS: ATs of the skin are rare neoplasms with benign tumors
being far more common. They are often misdiagnosed clinically, so histopathology
remains the gold standard for establishing an accurate diagnosis of skin ATs.
PMID- 28503345
TI - Awareness and Attitudes toward Organ Donation in Rural Puducherry, India.
AB - BACKGROUND: For many of the end-stage organ diseases, organ transplantation is
the most preferred treatment. The need for the organ transplantation is higher
than the availability. For the transplantation program to be successful,
awareness regarding organ donation is needed and people must have a positive
attitude toward donating organs. AIM: This study aims to assess the awareness and
attitudes regarding organ donation among the rural population and to evaluate the
sociodemographic factors associated with their awareness. SUBJECTS AND METHODS:
This community-based cross-sectional study was conducted among 360 people living
in 4 villages of Puducherry. Face-to-face interviews were carried out using
pretested questionnaire, which included the sociodemographic data. Data were
entered into Excel and analyzed using Statistical Package for Social Sciences.
RESULTS: Of 360 participants, 88% (317/360) were aware of organ donation. Among
these 317 participants, awareness was highest in the age group 18-30 years 98.8%
(87/88), male 91% (147/161), higher secondary and above 100% (58/58), and Class 1
socioeconomic status 92% (13/14). Source of awareness about organ donation was
primarily through media 83% (263/317). The majority of the participants 88%
(281/317) felt that the purpose of organ donation was to save life. Most of the
participants 91% (290/317) said that all healthy adults are eligible organ donors
and 87% (275/317) of the participants said that monetary benefits could not be
accepted for organ donation. Most of the participants 70% (223/317) were willing
to donate their organs after death. Among the participants who refused to donate
their organs, family refusal 57% (25/44) was the most common reason. CONCLUSION:
This study shows that there is a high level of awareness about organ donation
among rural people and most of the participants are willing to donate their
organs.
PMID- 28503346
TI - Color Stability of Heat-cure Acrylic Resin Subjected to Simulated Short-term
Immersion in Fast-acting Denture Cleansers.
AB - BACKGROUND: Regular usage of denture cleansers is recommended in complete denture
wearers for effective plaque control, and these cleansers alter the physical
properties of acrylic resin over a period of time. Thus, an in vitro study was
carried out to assess the effect of denture cleansers on the color stability of
heat-cure denture base resin. AIM: The aim of the present study was to evaluate
the effect of commercially available fast-acting denture cleansers on the color
stability of heat-cure denture base resin at different time intervals. MATERIALS
AND METHODS: Thirty-six heat-cure acrylic resin (Ivoclar Triplex Hot-V) specimens
are randomly allocated into four groups - Group A (distilled water as control);
Group B (polident - 3 min); Group C (fixodent scope plus); and Group D (stain
away plus) comprising of nine samples each. After recording the baseline values,
the specimens were immersed in their respective cleansing solutions for a
prescribed time interval. This procedure was repeated daily, and the color change
(DeltaE) was evaluated after 90 and 180 days interval using a colorimeter in a
standard "Commission International de l'Eclairage" color system. STATISTICAL
ANALYSIS USED: Paired t-test and Dunnett's T3 test. RESULTS: All the groups
exhibited a variable color change (DeltaE) for an immersion period of 90 days.
However, significant color differences (P = 0.001) were noticed among the test
groups after 180 days. CONCLUSION: The color change of denture base resin was
greater for Group D followed by Groups B, C, and A respectively after 180 days of
immersion. The DeltaE values of all test groups increased with time.
PMID- 28503347
TI - Wasting of Extensor Digitorum Brevis as a Decisive Preoperative Clinical
Indicator of Lumbar Canal Stenosis: A Single-center Prospective Cohort Study.
AB - BACKGROUND: The dilemma in managing patients with low back ache lies in
differentiating radiculopathy from lumbar canal stenosis. This has a huge bearing
in patients being planned for surgical intervention as underperforming leads to
failed back syndrome whereas over-doing leads to instability. There still remains
a loophole in clinically diagnosing lumbar canal stenosis. AIM: We opt to utilize
a simple bedside clinical examination in routinely assessing patients presenting
with low back ache in ruling out underlying canal stenosis. SUBJECTS AND METHODS:
We performed a prospective study on 120 consecutive patients presenting with low
back ache in the spine clinic. Each of them was neurologically examined and
thoroughly assessed for wasting of extensor digitorum brevis (EDB) muscles. These
were then correlated with the radio-imaging and the intraoperative findings.
RESULTS: Lumbar canal stenosis was mostly observed in the age group of 50-60
years. Diagnosis for L3/4 canal stenosis was made in 44/120 (36.6%), L5-S1 in
52/120 (43.3%), and L3/L4/L5 level in 48/120 (40%) of patients. EDB wasting was
seen unilaterally in 72/120 (60%) and bilaterally in 36/120 (30%) of the study
group. CONCLUSION: This study appraises the clinical implication of observing for
the wasting of EDB muscle so as to aid in the diagnosis of lumbar canal stenosis.
This simple bedside clinical pearl can help us in predicting the need of further
imaging studies and also in taking right therapeutic decision.
PMID- 28503348
TI - Emerging Trends in the Epidemiological Pattern of Head and Neck Cancers in Lagos,
Nigeria.
AB - BACKGROUND: Unfortunately, despite an increase in medical knowledge, survival
rates of head and neck cancers (HNCs) have not been observed to improve greatly.
This is true, especially in tumors located in obscure primary sites or late
presentation. AIM: The purpose of this study is to assess the epidemiologic
pattern of HNCs and to evaluate its emerging trends and patterns in Lagos state.
SUBJECTS AND METHODS: A retrospective study was conducted from 2003 to 2013 that
analyzed histologically diagnosed cases of HNC at the Pathology Departments of
the two tertiary teaching hospitals in Lagos. Data analysis was performed using
the Statistical Package for the Social Sciences (version 20) statistical
software. RESULTS: One thousand and eighty-three cases of head and neck
malignancies were recorded. A female: male ratio of 1.01:1 was reported with mean
age of 39.6 (standard deviation 21.1) years. The oral cavity was the most
affected anatomic site (21.2%, 230/1083) in the period under review. Malignant
epithelial tumors accounted for 72% (779/1083) of cases seen. Carcinomas were the
most common histological variant seen (67%, 726/1083) and squamous cell carcinoma
accounted for 58% (421/726) of carcinomas recorded. Oral cavity malignancies
(21.8%, 118/540) were the most common in males while thyroid malignancies (28.5%,
155/543) were the most seen in females. In children (<=15 years), the most common
histologic findings were carcinomas (42.3%; 77/182) and retinoblastomas (23.6%;
43/182). CONCLUSION: Epithelial malignancies were the most common malignancy in
the study, and the oral cavity appears to be the increasingly predominant site
for HNCs. A changing pattern in gender predominance, age distribution, and
frequency with histological variants and anatomical sites was also observed in
this study.
PMID- 28503349
TI - Medial Malleolar Fractures: An Anatomic Survey Determining the Ideal Screw
Length.
AB - BACKGROUND: Medial malleolar fractures are frequent, and their treatment is
familiar to the orthopedic surgeon. Lag screw fixation using partially threaded
screws remains the standard treatment method for medial malleolar fractures.
However, the literature lacks a defined method for selecting lag screw length,
relying more so on the empiric choice of the surgeon. AIM: The aim of this study
is to help define the ideal lag screw length for medial melleolar fracture
fixation. MATERIALS AND METHODS: One hundred and sixteen anatomic specimens were
included in the study. A transverse cut was performed in the distal third of the
tibia, roughly 1 and a half times the distal tibial plafond width from the ankle
joint. A coronal cut was then performed using the center of the medial malleolus.
Three observers measured the distance between the medial malleolus tip and
beginning of the medullary canal in all anatomic specimens. Differences in
measurements were statistically compared, level of (P <= 0.05). Interclass
correlation coefficient (ICC) significance level was set at P < 0.05. RESULTS:
Measurement average was 55 mm between the medial malleolus tip and the medullary
canal, with a standard deviation of 10 mm. High concordance (ICC: 0.819) was
achieved among all pairs of observers (P < 0.01). The systematic difference among
measurements was absent, and random distribution around general measurements was
observed. CONCLUSION: The authors recommend a screw length of no more than 45 mm
to optimize the location of the screw threads in the best cancellous bone in an
effort to obtain the most compression.
PMID- 28503350
TI - Clinicoradiologic Profile of Involvement and Healing in Tuberculosis of the
Spine.
AB - BACKGROUND: There is no much information about how tuberculous lesions of the
spine progress/heal; what clinical and radiological features suggest
progression/healing; what is the optimal duration of antitubercular treatment;
and what clinical, laboratory, and radiological investigations and their
frequency should be done to monitor the disease course. AIMS: The present study
aimed to evaluate what specific clinicoradiologic features suggest involvement
and healing in tuberculosis of the spine. SUBJECTS AND METHODS: Fifty spinal
tuberculosis patients (30 males and 20 females) diagnosed clinicoradiologically
were enrolled in the study. Patients were evaluated clinically, radiographically,
and by magnetic resonance imaging (MRI) at regular intervals to monitor the
disease course till 24 months of the initial presentation. RESULTS:
Wedge/collapse (23/50 cases), soft tissue mass (29/50 cases), disc narrowing
(45/54 discs), and endplate erosions (89/107 endplates) were the plain
radiological findings of tubercular spinal involvement. Earliest sign of healing
on plain radiography was decrease in fuzziness of endplate, ultimately leading to
either sclerosis of endplate or fusion of adjacent vertebrae. Initial MRI
findings included bone marrow edema (50/50 cases), discitis (53/62 discs),
endplate erosions (105/123 endplates), pre- and para-vertebral collections (45/50
cases), epidural involvement (26/50 cases), epidural spread (77/109 vertebrae),
and subligamentous spread (42/50 cases). Earliest feature of healing on magnetic
resonance (MR) examination was decrease in inflammatory soft-tissue masses and
reduction in marrow edema. CONCLUSIONS: Salient features of spinal involvement in
tuberculosis on plain radiograph were paradiscal involvement, endplate
destruction, and soft tissue masses. Marrow edema, paravertebral collections,
subligamentous spread, extradural component, endplate erosion, and discitis
suggested tubercular involvement of the spine on MRI. A decrease in these was
observed to have prognostic value both in monitoring disease course and response
to chemotherapy. Based on the clinicoradiologic findings of the present study, we
propose decision-making algorithm, follow-up algorithm, and MR examination
protocol for spinal tuberculosis. LEVEL OF EVIDENCE: This was a Level II study.
PMID- 28503351
TI - Subtrochanteric and Distal Femur Fractures in a Patient with Femoral Shaft
Fracture Malunion and Knee Disarticulation: A Rare and Challenging Case Report.
AB - This study aims to describe a rare and challenging case of a patient who
presented ipsilateral subtrochanteric and distal femur fractures due to low
energy trauma. The peculiarity of this case is the presence of femoral shaft
fracture malunion and knee disarticulation in the same limb resulting from an
accident suffered 30 years ago. The patient underwent femoral diaphyseal
osteotomy and fixation of the subtrochanteric and distal femur fractures with a
long cephalomedullary nail and distal femur locking plate, respectively. Despite
the magnitude of the surgical procedure, all fractures healed, preserving the
femoral length with the absence of infection and clinical complications. There
was an improvement of the preinjury function attributed to the osteotomy of the
femoral diaphyseal, which alleviated the anterior thigh discomfort.
PMID- 28503352
TI - Serum Adiponectin Levels are Associated with Microcirculatory Function, but not
with Coronary Artery Disease in the Young.
PMID- 28503353
TI - A Systematic Review of Reproductive Coercion in International Settings.
AB - Reproductive coercion is behavior that interferes with a woman's autonomous
reproductive decision-making. It may take the form of birth control sabotage,
pregnancy coercion, or controlling the outcome of a pregnancy. Perpetrators may
be partners, a partner's family, or the woman's family. This article reviews the
literature on reproductive coercion in international settings. In this review of
10 research studies, findings are presented on prevalence and type of
reproductive coercion, associated factors, specific tactics, relationship with
intimate partner violence and domestic violence (in-laws particularly), and
implications for women's reproductive health. Findings highlight reproductive
coercion as a subset of intimate partner violence that is poorly understood,
especially in international settings. More research is needed on protective
factors, how interventions can capitalize on protective factors, and the
strategies women use to resist reproductive coercion. Policy implications and
recommendations are discussed with particular attention to issues related to
diverse social and cultural environments.
PMID- 28503354
TI - Mechanism of the P450-Catalyzed Oxidative Cyclization in the Biosynthesis of
Griseofulvin.
AB - Griseofulvin is an anti-fungal agent which has recently been determined to have
potential anti-viral and anti-cancer applications. The role of specific enzymes
involved in the biosynthesis of this natural product has previously been
determined, but the mechanism by which a p450, GsfF, catalyzes the key oxidative
cyclization of griseophenone B remains unknown. Using density functional theory
(DFT), we have determined the mechanism of this oxidation that forms the oxa
spiro core of griseofulvin. Computations show GsfF preferentially performs two
sequential phenolic O-H abstractions rather than epoxidation to form an arene
oxide intermediate. This conclusion is supported by experimental kinetic isotope
effects.
PMID- 28503356
TI - Towards an Obesity-Cancer Knowledge Base: Biomedical Entity Identification and
Relation Detection.
AB - Obesity is associated with increased risks of various types of cancer, as well as
a wide range of other chronic diseases. On the other hand, access to health
information activates patient participation, and improve their health outcomes.
However, existing online information on obesity and its relationship to cancer is
heterogeneous ranging from pre-clinical models and case studies to mere
hypothesis-based scientific arguments. A formal knowledge representation (i.e., a
semantic knowledge base) would help better organizing and delivering quality
health information related to obesity and cancer that consumers need.
Nevertheless, current ontologies describing obesity, cancer and related entities
are not designed to guide automatic knowledge base construction from
heterogeneous information sources. Thus, in this paper, we present methods for
named-entity recognition (NER) to extract biomedical entities from scholarly
articles and for detecting if two biomedical entities are related, with the long
term goal of building a obesity-cancer knowledge base. We leverage both
linguistic and statistical approaches in the NER task, which supersedes the state
of-the-art results. Further, based on statistical features extracted from the
sentences, our method for relation detection obtains an accuracy of 99.3% and a f
measure of 0.993.
PMID- 28503357
TI - How Bad Is It? Usefulness of the "7eed Model" for Scoring Severity and Level of
Need in Complex Emergencies.
AB - BACKGROUND: Humanitarian assistance is designated to save lives and alleviate
suffering among people affected by disasters. In 2014, close to 25 billion USD
was allocated to humanitarian assistance, more than 80% of it from governmental
donors and EU institutions. Most of these funds are devoted to Complex
Emergencies (CE). It is widely accepted that the needs of the affected population
should be the main determinant for resource allocations of humanitarian funding.
However, to date no common, systematic, and transparent system for needs-based
allocations exists. In an earlier paper, an easy-to-use model, "the 7eed model",
based on readily available indicators that distinguished between levels of
severity among disaster-affected countries was presented. The aim of this paper
is to assess the usefulness of the 7eed model in regards to 1) data availability,
2) variations between CE effected countries and sensitivity to change over time,
and 3) reliability in capturing severity and levels of need. METHOD: We applied
the 7eed model to 25 countries with CE using data from 2013 to 2015. Data
availability and indicator value variations were assessed using heat maps. To
calculate a severity score and a needs score, we applied a standardised
mathematical formula, based on the UTSTEIN template. We assessed the model for
reliability on previous CEs with a "known" outcome in terms of excess mortality.
RESULTS: Most of the required data was available for nearly all countries and
indicators, and availability increased over time. The 7eed model was able to
discriminate between levels of severity and needs among countries. Comparison
with historical complex disasters showed a correlation between excess mortality
and severity score. CONCLUSION: Our study indicates that the proposed 7eed model
can serve as a useful tool for setting funding levels for humanitarian assistance
according to measurable levels of need. The 7eed model provides national level
information but does not take into account local variations or specific
contextual factors.
PMID- 28503355
TI - Stereoselective cis-Vinylcyclopropanation via a Gold(I)-Catalyzed Retro-Buchner
Reaction under Mild Conditions.
AB - A highly stereoselective gold(I)-catalyzed cis-vinylcyclopropanation of alkenes
has been developed. Allylic gold carbenes, generated via a retro-Buchner reaction
of 7-alkenyl-1,3,5-cycloheptatrienes, react with alkenes to form
vinylcyclopropanes. The gold(I)-catalyzed retro-Buchner reaction of these
substrates proceeds by simple heating at a temperature much lower than that
required for the reaction of 7-aryl-1,3,5-cycloheptatrienes (75 degrees C vs 120
degrees C). A newly developed Julia-Kocienski reagent enables the synthesis of
the required cycloheptatriene derivatives in one step from readily available
aldehydes or ketones. On the basis of mechanistic investigations, a
stereochemical model for the cis selectivity was proposed. An unprecedented gold
catalyzed isomerization of cis- to trans-cyclopropanes has also been discovered
and studied by DFT calculations.
PMID- 28503358
TI - Behavior Problems and Post-traumatic Stress Symptoms in Children Beginning
School: A Comparison of Pre- and Post-Earthquake Groups.
AB - INTRODUCTION: Literature reviews caution that estimating the effects of disasters
on the behavior of children following a disaster is difficult without baseline
information and few studies report the effects of earthquakes on young children.
In addition the relationship between age at the time of disaster and
consequential behavior problems have not been reported for young children who
experience disaster-related stress during a developmentally sensitive period.
METHODS: Behavior problems and symptoms of post-traumatic stress (PTS) were
reported for two groups of children from nearby neighborhoods during their first
term at school, using the Behavior Problem Index by teacher report, following
approved informed consent procedures. Data on one group, "Pre-EQ" (N=297), was
collected four years before the beginning of the earthquakes on children born
2001-2002. Data on the second group, "Post-EQ" (N=212), was collected
approximately three to four years after the beginning of the earthquakes on
children born 2007-2009 and living in heavily damaged neighborhoods. The Post-EQ
group had significantly more children from high socioeconomic neighborhoods but
no other significant differences on main demographic characteristics. RESULTS:
The mean behavior problem score was significantly higher in the Post-EQ group
(Mean =6.11) as compared to the Pre-EQ group (Mean = 3.78). PTS symptoms were
also significantly higher in the Post-EQ group (Mean =2.91) as compared to the
Pre-EQ group (Mean=1.98) and more children had high PTS scores (20.9% v. 8.8%,
OR= 2.73, 95%CI =1.57, 4.76). Model testing identified that a younger age at the
time of exposure was the only significant predictor of high numbers of PTS
symptoms in the Post-EQ group. Discussion: Rates of teacher-reported behavior
problems in young children more than doubled following the Christchurch
earthquakes. Younger children may be more vulnerable to the effects of
earthquakes that occur during a developmentally sensitive period. Additional
research is needed to consider the effects of age and duration of disaster
effects to better understand the effects of disasters on children, their families
and communities.
PMID- 28503359
TI - Maintaining Maternal and Child Health Services During the Ebola Outbreak:
Experience from Pujehun, Sierra Leone.
AB - BACKGROUND: During the Ebola outbreak the overall confidence of the population in
the national health system declined in Sierra Leone, with a reduction in the use
of health services. The objective of this study is to provide information on
understanding of how Ebola impacted maternal and child health services in Sierra
Leone. Data come from an operational setting which is representative of the
communities affected by the outbreak. METHODS: By integrating hospital registers
and contact tracing form data with healthcare workers and local population
interviews, the transmission chain was reconstructed. Data on the utilization of
maternal and neonatal health services were collected from the local district's
Health Management Information System. The main measures put in place to control
the Ebola epidemic were: the organization of a rapid response to the crisis by
the local health authorities; triage, contact tracing and quarantine; isolation,
clinical management and safe burials; training and community sensitization.
RESULTS: A total of 49 case patients were registered between July and November
2014 in the Pujehun district. Hospitalization rate was 89%. Overall, 74.3% of
transmission events occurred between members of the same family, 17.9% in the
community and 7.7% in hospital. The mean number of contacts investigated per case
raised from 11.5 in July to 25 in September 2014. The 2014 admission trend in the
pediatric ward shows a decrease after beginning of June: the reduction was almost
significant in the period July-December (p 0.05). The admission in the maternity
ward showed no statistical differences in comparison with the previous year (p
0.07). Also the number of deliveries appeared to be similar to the previous year,
without significant variations (p 0.41). CONCLUSION: The Ebola outbreak reduced
the number of patients at hospital level in Pujehun district. However, the
activities undertaken to manage Ebola, reduced the spread of infection and the
impact of the disease in mothers and children. A number of reasons which may
explain these results are presented and discussed.
PMID- 28503360
TI - Risk Criteria in Hospital Site Selection: A Systematic Review.
AB - INTRODUCTION: Hospitals should be safe and remain functional in emergencies and
disasters as it is mentioned in the Sendai Framework. Proper selection of a
hospital location has a direct effect on survival of affected population in
disasters as well as cost and benefit of the hospital in non-emergency situation.
Different studies applied different criteria for Hospital Site Selection (HSS).
The present study through a systematic review aimed to find out a categorized
criteria list that have been used for (HSS) in the literature. METHODS: In
accordance with the PRISMA statement, "PubMed", "ScienceDirect", "Google
Scholar", and "Scopus" were searched up to end of 2015. All English Articles that
were published in peer-reviewed journals and had discussed site selection
criteria for hospitals were included. Out of 41 articles, 15 met the inclusion
criteria in which 39 general criteria for HSS were applied. These criteria were
categorized in six main groups including cost, demand, environmental,
administrative, disaster risk, and "other" concerns through a focus group
discussion. RESULTS: Accordingly, the application percentage of cost, demand,
environmental, administrative, disaster risk, and "other" concerns in the
articles was 100, 93.3, 53.3, 33.3, 20.0, and 13.3 respectively. The least
devoted attention was to disaster risk issues. DISCUSSION: Few researchers
applied risk related criteria for HSS. Further consideration of "risk of hazards"
and "burden of diseases" in comprehensive studies, is recommended for HSS to
guide the decision makers for building more resilient hospitals. Keywords
Hospital, Site selection, Systematic review, Disaster risk.
PMID- 28503361
TI - A Review of the Key Considerations in Mental Health Services Research: A Focus on
Low-Income Children and Families.
AB - Children have been particularly vulnerable to the economic challenges of the past
decade, with half (45 to 51%) of children under the age of 18 living in a low
income home and nearly 22% of those living in poverty. Low-income children are
overrepresented in a range of statistics on psychosocial maladjustment issues,
but their families are less likely than other socioeconomic groups to participate
in mental health services and intervention research. Thus, this review asserts
that substantive advances in mental health services and intervention research
with low income families must move beyond a between-group, deficit-focused
perspective to a more nuanced contemplation of how to: 1) Operationalize the
"income" in low-income families; 2) Disentangle the interrelationship of low
income, race, and ethnicity; and 3) Optimize recruitment, engagement and
retention efforts via sensitivity to the culture of low-income status. Examples
of mental health services and intervention research with low-income families will
be discussed, and a summary, conclusions, and directions for future research are
discussed in the context of these recommendations.
PMID- 28503362
TI - A Case of Myoclonus-Dystonia Responding to Low-frequency Pallidal Stimulation.
AB - BACKGROUND: High-frequency pallidal stimulation has been shown to improve various
types of dystonia, including myoclonus-dystonia. CASE REPORT: We report a case of
epsilon sarcoglycan mutation-negative myoclonus-dystonia with response to low
frequency bilateral pallidal stimulation. DISCUSSION: Low-frequency pallidal
stimulation provides an effective means of treating various dystonias, regardless
of genetic status, as in our case, as it provides increased programming options
with fewer adverse effects.
PMID- 28503363
TI - Focused Ultrasound for Essential Tremor: Review of the Evidence and Discussion of
Current Hurdles.
AB - BACKGROUND: While there is no breakthrough progress in the medical treatment of
essential tremor (ET), in the past decades several remarkable achievements
happened in the surgical field, such as radiofrequency thalamotomy, thalamic deep
brain stimulation, and gamma knife thalamotomy. The most recent advance in this
area is magnetic resonance-guided focused ultrasound (MRgFUS). METHODS: The
purpose of this review is to discuss the new developments and trials of MRgFUS in
the treatment of ET and other tremor disorders. RESULTS: MRgFUS is an
incisionless surgery performed without anesthesia and ionizing radiation (no risk
of cumulative dose and delayed side effects). Studies have shown the safety and
effectiveness of unilateral MRgFUS-thalamotomy in the treatment of ET. It has
been successfully used in a few patients with Parkinson's disease-related tremor,
and in fewer patients with fragile X-associated tremor/ataxia syndrome. The
safety and long-term effects of the procedure are still unclear, as temporary and
permanent adverse events have been reported as well as recurrence of tremor.
DISCUSSION: MRgFUS is a promising new surgical approach with a number of unknowns
and unsolved issues. It represents a valuable option particularly for patients
who refused or could not be candidates for other procedures, deep brain
stimulation in particular.
PMID- 28503364
TI - Human as the Ultimate Wound Healing Model: Strategies for Studies Investigating
the Dermal Lipidome.
AB - PURPOSE OF REVIEW: Educate the reader of the multiple roles undertaken by the
human epidermal lipidome and the experimental techniques of measuring them.
RECENT FINDINGS: Damage to skin elicits a wound healing process that is capped by
the recreation of the lipid barrier. In addition to barrier function, lipids also
undertake an active signaling role during wound healing. Achievement of these
multiple functions necessitates a significant complexity and diversity in the
lipidome resulting in a composition that is unique to the human skin. As such,
any attempts to delineate the function of the lipidome during the wound healing
process in humans need to be addressed via studies undertaken in humans. SUMMARY:
The human cutaneous lipidome is unique and play a functionally significant role
in maintaining barrier and regulating wound healing. Modern mass spectrometry and
Raman spectroscopy based methods enable the investigation epidermal lipidome with
respect to those functions.
PMID- 28503365
TI - Genetics, Diagnosis, and Monitoring of Pseudoexfoliation Glaucoma.
AB - Recent studies have shed new light on the genetic factors underlying
pseudoexfoliation syndrome, growing our understanding of the role of the lysyl
oxidase-like 1 (LOXL1) gene and its various polymorphisms as well as identifying
new genetic associations. Recent years have brought new insight on how these
genetic factors interact with other factors, including environmental, to confer
risk to individuals and populations worldwide. All of these findings may hold
importance to the screening, diagnosis, and monitoring of pseudoexfoliation and
may also help lead to the identification of novel therapeutic targets. This
review serves as an update on the recent trends and findings in pseudoexfoliation
syndrome.
PMID- 28503366
TI - Is Trauma Memory Special? Trauma Narrative Fragmentation in PTSD: Effects of
Treatment and Response.
AB - Seminal theories posit that fragmented trauma memories are critical to
posttraumatic stress disorder (PTSD; van der Kolk & Fisler, 1995; Brewin, 2014)
and that elaboration of the trauma narrative is necessary for recovery (e.g.,
Foa, Huppert, & Cahill, 2006). According to fragmentation theories, trauma
narrative changes, particularly for those receiving trauma-focused treatment,
should accompany symptom reduction. Trauma and control narratives in 77 men and
women with chronic PTSD were examined pre- and post-treatment, comparing
prolonged exposure (PE) and sertraline. Utilizing self-report, rater coding, and
objective coding of narrative content, fragmentation was compared across
narrative types (trauma, negative, positive) by treatment modality and response,
controlling for potential confounds. Although sensory components increased with
PE (d = 0.23 - 0.44), there were no consistent differences in fragmentation from
pre- to post-treatment between PE and sertraline or treatment responders and non
responders. Contrary to theories, changes in fragmentation may not be a crucial
mechanism underlying PTSD therapeutic recovery.
PMID- 28503367
TI - Etiology of Triarchic Psychopathy Dimensions in Chimpanzees (Pan troglodytes).
AB - The current study undertook analyses of genealogical data from a sample of 178
socially-housed chimpanzees (Pan troglodytes) with well-documented pedigrees, to
clarify the etiologic bases of triarchic psychopathy dimensions and the influence
of early social rearing experiences. Whereas biometric analyses for the full
sample indicated significant heritability for the boldness dimension of
psychopathy only, heritability estimates varied by early rearing, with all three
triarchic dimensions showing significant heritabilities among mother-reared but
not nursery-reared apes. For mother-reared apes, both genes and environment
contributed to covariance between meanness and disinhibition, whereas environment
contributed mainly to covariation between these dimensions and boldness. Results
indicate contributions of both genes and environment to psychopathic tendencies,
with an important role for early-rearing in their relative contributions to
distinct phenotypic subdimensions. In conjunction with findings from human
studies, results provide valuable insights into core biobehavioral processes
relevant to psychological illness and health.
PMID- 28503369
TI - Direct evidence of megamammal-carnivore interaction decoded from bone marks in
historical fossil collections from the Pampean region.
AB - Pleistocene South American megafauna has traditionally attracted the interest of
scientists and the popular media alike. However, ecological interactions between
the species that inhabited these ecosystems, such as predator-prey relationships
or interspecific competition, are poorly known. To this regard, carnivore marks
imprinted on the fossil bones of megamammal remains are very useful for
deciphering biological activity and, hence, potential interspecific relationships
among taxa. In this article, we study historical fossil collections housed in
different European and Argentinean museums that were excavated during the 19th
and early 20th centuries in the Pampean region, Argentina, in order to detect
carnivore marks on bones of megamammals and provide crucial information on the
ecological relationships between South American taxa during the Pleistocene. Our
results indicate that the long bones of megafauna from the Pampean region (e.g.,
the Mylodontidae and Toxodontidae families) exhibit carnivore marks. Furthermore,
long bones of medium-sized species and indeterminate bones also present
punctures, pits, scores and fractures. Members of the large-carnivore guild, such
as ursids, canids and even felids, are recognised as the main agents that
inflicted the marks. We hypothesize that the analysed carnivore marks represent
the last stages of megaherbivore carcass exploitation, suggesting full
consumption of these animals by the same or multiple taxa in a hunting and/or
scavenging scenario. Moreover, our observations provide novel insights that help
further our understanding of the palaeoecological relationships of these unique
communities of megamammals.
PMID- 28503370
TI - Cave features, seasonality and subterranean distribution of non-obligate cave
dwellers.
AB - Seasonality impacts species distributions through changes of the environmental
conditions that affect the presence of individuals at a given place. Although the
dynamics of cave microclimates are well known, only a few studies have evaluated
the effects of such dynamics on non-strictly cave species. Here we assessed if
species exploiting subterranean environments show changes in habitat occupation
related to seasonal variation of cave microclimates. We surveyed 16 caves in
central Italy every month for one year. Caves were subdivided into longitudinal
sectors of three meters. In each sector we measured cave morphology and
microclimatic features, assessed the occurrence of eight non-troglobitic taxa
(orthopterans, spiders, gastropods and amphibians), and related species
distribution to environmental features and sampling periods. The occurrence of
most species was related to both cave morphology and microclimatic features. The
survey month was the major factor determining the presence of species in cave
sectors, indicating that cave-dwelling taxa show strong seasonality in activity
and distribution. For multiple species, we detected interactions between sampling
period and microclimatic features, suggesting that species may associate with
different microhabitats throughout the year. The richest communities were found
in sites with specific microclimates (i.e., high humidity, warm temperature and
low light) but seasonality for species richness was strong as well, stressing the
complexity of interactions between outdoor and subterranean environments.
PMID- 28503368
TI - Running wheel training does not change neurogenesis levels or alter working
memory tasks in adult rats.
AB - BACKGROUND: Exercise can change cellular structure and connectivity (neurogenesis
or synaptogenesis), causing alterations in both behavior and working memory. The
aim of this study was to evaluate the effect of exercise on working memory and
hippocampal neurogenesis in adult male Wistar rats using a T-maze test. METHODS:
An experimental design with two groups was developed: the experimental group (n =
12) was subject to a forced exercise program for five days, whereas the control
group (n = 9) stayed in the home cage. Six to eight weeks after training, the
rats' working memory was evaluated in a T-maze test and four choice days were
analyzed, taking into account alternation as a working memory indicator.
Hippocampal neurogenesis was evaluated by means of immunohistochemistry of BrdU
positive cells. RESULTS: No differences between groups were found in the
behavioral variables (alternation, preference index, time of response, time of
trial or feeding), or in the levels of BrdU positive cells. DISCUSSION: Results
suggest that although exercise may have effects on brain structure, a construct
such as working memory may require more complex changes in networks or
connections to demonstrate a change at behavioral level.
PMID- 28503371
TI - Transcriptome sequencing and SNP detection in Phoebe chekiangensis.
AB - BACKGROUND: Phoebe chekiangensis is a rare tree species that is only distributed
in south-eastern China. Although this species is famous for its excellent wood
properties, it has not been extensively studied at the molecular level. RESULTS:
Here, the transcriptome of P. chekiangensis was sequenced using next-generation
sequencing technology, and 75,647 transcripts with 48,011 unigenes were assembled
and annotated. In addition, 162,938 putative single nucleotide polymorphisms
(SNPs) were predicted and 25 were further validated using the Sanger method.
CONCLUSION: The currently available SNP prediction software packages showed low
levels of correspondence when compared. The transcriptome and SNPs will
contribute to the exploration of P. chekiangensis genetic resources and the
understanding of its molecular mechanisms.
PMID- 28503372
TI - Endosymbiont interference and microbial diversity of the Pacific coast tick,
Dermacentor occidentalis, in San Diego County, California.
AB - The Pacific coast tick, Dermacentor occidentalis Marx, is found throughout
California and can harbor agents that cause human diseases such as anaplasmosis,
ehrlichiosis, tularemia, Rocky Mountain spotted fever and rickettsiosis 364D.
Previous studies have demonstrated that nonpathogenic endosymbiotic bacteria can
interfere with Rickettsia co-infections in other tick species. We hypothesized
that within D. occidentalis ticks, interference may exist between different
nonpathogenic endosymbiotic or nonendosymbiotic bacteria and Spotted Fever group
Rickettsia (SFGR). Using PCR amplification and sequencing of the rompA gene and
intergenic region we identified a cohort of SFGR-infected and non-infected D.
occidentalis ticks collected from San Diego County. We then amplified a partial
segment of the 16S rRNA gene and used next-generation sequencing to elucidate the
microbiomes and levels of co-infection in the ticks. The SFGR R. philipii str.
364D and R. rhipicephali were detected in 2.3% and 8.2% of the ticks,
respectively, via rompA sequencing. Interestingly, next generation sequencing
revealed an inverse relationship between the number of Francisella-like
endosymbiont (FLE) 16S rRNA sequences and Rickettsia 16S rRNA sequences within
individual ticks that is consistent with partial interference between FLE and
SFGR infecting ticks. After excluding the Rickettsia and FLE endosymbionts from
the analysis, there was a small but significant difference in microbial community
diversity and a pattern of geographic isolation by distance between collection
locales. In addition, male ticks had a greater diversity of bacteria than female
ticks and ticks that weren't infected with SFGR had similar microbiomes to canine
skin microbiomes. Although experimental studies are required for confirmation,
our findings are consistent with the hypothesis that FLEs and, to a lesser
extent, other bacteria, interfere with the ability of D. occidentalis to be
infected with certain SFGR. The results also raise interesting possibilities
about the effects of putative vertebrate hosts on the tick microbiome.
PMID- 28503373
TI - Analysis of genomic variation in lung adenocarcinoma patients revealed the
critical role of PI3K complex.
AB - BACKGROUND: Molecularly targeted therapies improved survival status of some
patients with lung adenocarcinoma, which accounts for 40% of all lung cancers,
and in-depth study of gene alterations is important for the personalized
treatment. METHODS: The legacy archive data of clinical information and genomic
variations under the project TCGA Lung Adenocarcinoma were downloaded from the
GDC Data Portal using R package TCGAbiolinks. The significantly aberrant copy
number variants segments were figured out using GAIA. After annotation, the genes
involving CNV were used to get enriched pathways. Recurrent amplifications and
deletions were identified and visualized by OncoPrint. Genomic alterations in
cancer, including CNV and mutations, were represented in Circos. RESULTS: The
significantly aberrant CNV segments were found, and the genes involved were
associated with the immune system. In an analysis of 517 mutation annotated
files, we highlighted 63 highly recurrent mutated genes which were associated
with lung cancer signaling. These genes involved in important pathways related to
cancer progression. The intersections between the genes involving in the
significantly aberrant CNV and the genes harboring recurrent somatic SNP were
extracted. The PI3K protein family acted as critical roles in the lung
adenocarcinoma, since the components of the PI3K protein family include PIK3C2B,
PIK3CA, PIK3R1 and so forth were presented in the intersections. CONCLUSION: We
represented a comprehensive annotation of genomic alterations in lung
adenocarcinoma and proposed that PI3K signaling proteins were critical for it.
PMID- 28503374
TI - Sooty tern (Onychoprion fuscatus) survival, oil spills, shrimp fisheries, and
hurricanes.
AB - Migratory seabirds face threats from climate change and a variety of
anthropogenic disturbances. Although most seabird research has focused on the
ecology of individuals at the colony, technological advances now allow
researchers to track seabird movements at sea and during migration. We combined
telemetry data on Onychoprion fuscatus (sooty terns) with a long-term capture
mark-recapture dataset from the Dry Tortugas National Park to map the movements
at sea for this species, calculate estimates of mortality, and investigate the
impact of hurricanes on a migratory seabird. Included in the latter analysis is
information on the locations of recovered bands from deceased individuals wrecked
by tropical storms. We present the first known map of sooty tern migration in the
Atlantic Ocean. Our results indicate that the birds had minor overlaps with areas
affected by the major 2010 oil spill and a major shrimp fishery. Indices of
hurricane strength and occurrence are positively correlated with annual mortality
and indices of numbers of wrecked birds. As climate change may lead to an
increase in severity and frequency of major hurricanes, this may pose a long-term
problem for this colony.
PMID- 28503375
TI - Network science meets respiratory medicine for OSAS phenotyping and severity
prediction.
AB - Obstructive sleep apnea syndrome (OSAS) is a common clinical condition. The way
that OSAS risk factors associate and converge is not a random process. As such,
defining OSAS phenotypes fosters personalized patient management and population
screening. In this paper, we present a network-based observational, retrospective
study on a cohort of 1,371 consecutive OSAS patients and 611 non-OSAS control
patients in order to explore the risk factor associations and their correlation
with OSAS comorbidities. To this end, we construct the Apnea Patients Network
(APN) using patient compatibility relationships according to six objective
parameters: age, gender, body mass index (BMI), blood pressure (BP), neck
circumference (NC) and the Epworth sleepiness score (ESS). By running targeted
network clustering algorithms, we identify eight patient phenotypes and
corroborate them with the co-morbidity types. Also, by employing machine learning
on the uncovered phenotypes, we derive a classification tree and introduce a
computational framework which render the Sleep Apnea Syndrome Score (SASScore);
our OSAS score is implemented as an easy-to-use, web-based computer program which
requires less than one minute for processing one individual. Our evaluation,
performed on a distinct validation database with 231 consecutive patients,
reveals that OSAS prediction with SASScore has a significant specificity
improvement (an increase of 234%) for only 8.2% sensitivity decrease in
comparison with the state-of-the-art score STOP-BANG. The fact that SASScore has
bigger specificity makes it appropriate for OSAS screening and risk prediction in
big, general populations.
PMID- 28503377
TI - Analysis of RecA-independent recombination events between short direct repeats
related to a genomic island and to a plasmid in Escherichia coli K12.
AB - RecA-independent recombination events between short direct repeats, leading to
deletion of the intervening sequences, were found to occur in two genetic models
in the Escherichia coli K12 background. The first model was a small E. coli
genomic island which had been shown to be mobile in its strain of origin and,
when cloned, also in the E. coli K12 context. However, it did not encode a site
specific recombinase as mobile genomic islands usually do. It was then deduced
that the host cells should provide the recombination function. This latter was
searched for by means of a PCR approach to detect the island excision in E. coli
K12 mutants affected in a number of recombination functions, including the 16 E.
coli K12 site-specific recombinases, the RecET system, and multiple proteins that
participate in the RecA-dependent pathways of homologous recombination. None of
these appeared to be involved in the island excision. The second model, analyzed
in a RecA deficient context, was a plasmid construction containing a short direct
repeat proceeding from Saccharomyces cerevisiae, which flanked the cat gene. The
excision of this gene by recombination of the DNA repeats was confirmed by PCR
and through the detection, recovery and characterization of the plasmid deleted
form. In sum, we present new evidence on the occurrence of RecA-independent
recombination events in E. coli K12. Although the mechanism underlying these
processes is still unknown, their existence suggests that RecA-independent
recombination may confer mobility to other genetic elements, thus contributing to
genome plasticity.
PMID- 28503376
TI - Toward a better understanding of the mechanisms of symbiosis: a comprehensive
proteome map of a nascent insect symbiont.
AB - Symbiotic bacteria are common in insects and can affect various aspects of their
hosts' biology. Although the effects of insect symbionts have been clarified for
various insect symbiosis models, due to the difficulty of cultivating them in
vitro, there is still limited knowledge available on the molecular features that
drive symbiosis. Serratia symbiotica is one of the most common symbionts found in
aphids. The recent findings of free-living strains that are considered as nascent
partners of aphids provide the opportunity to examine the molecular mechanisms
that a symbiont can deploy at the early stages of the symbiosis (i.e., symbiotic
factors). In this work, a proteomic approach was used to establish a
comprehensive proteome map of the free-living S. symbiotica strain CWBI-2.3T.
Most of the 720 proteins identified are related to housekeeping or primary
metabolism. Of these, 76 were identified as candidate proteins possibly promoting
host colonization. Our results provide strong evidence that S. symbiotica CWBI
2.3T is well-armed for invading insect host tissues, and suggest that certain
molecular features usually harbored by pathogenic bacteria are no longer present.
This comprehensive proteome map provides a series of candidate genes for further
studies to understand the molecular cross-talk between insects and symbiotic
bacteria.
PMID- 28503378
TI - Pollen extracts and constituent sugars increase growth of a trypanosomatid
parasite of bumble bees.
AB - Phytochemicals produced by plants, including at flowers, function in protection
against plant diseases, and have a long history of use against trypanosomatid
infection. Floral nectar and pollen, the sole food sources for many species of
insect pollinators, contain phytochemicals that have been shown to reduce
trypanosomatid infection in bumble and honey bees when fed as isolated compounds.
Nectar and pollen, however, consist of phytochemical mixtures, which can have
greater antimicrobial activity than do single compounds. This study tested the
hypothesis that pollen extracts would inhibit parasite growth. Extracts of six
different pollens were tested for direct inhibitory activity against cell
cultures of the bumble bee trypanosomatid gut parasite Crithidia bombi.
Surprisingly, pollen extracts increased parasite growth rather than inhibiting
it. Pollen extracts contained high concentrations of sugars, mainly the
monosaccharides glucose and fructose. Experimental manipulations of growth media
showed that supplemental monosaccharides (glucose and fructose) increased maximum
cell density, while a common floral phytochemical (caffeic acid) with inhibitory
activity against other trypanosomatids had only weak inhibitory effects on
Crithidia bombi. These results indicate that, although pollen is essential for
bees and other pollinators, pollen may promote growth of intestinal parasites
that are uninhibited by pollen phytochemicals and, as a result, can benefit from
the nutrients that pollen provides.
PMID- 28503379
TI - A public dataset of running biomechanics and the effects of running speed on
lower extremity kinematics and kinetics.
AB - BACKGROUND: The goals of this study were (1) to present the set of data
evaluating running biomechanics (kinematics and kinetics), including data on
running habits, demographics, and levels of muscle strength and flexibility made
available at Figshare (DOI: 10.6084/m9.figshare.4543435); and (2) to examine the
effect of running speed on selected gait-biomechanics variables related to both
running injuries and running economy. METHODS: The lower-extremity kinematics and
kinetics data of 28 regular runners were collected using a three-dimensional (3D)
motion-capture system and an instrumented treadmill while the subjects ran at 2.5
m/s, 3.5 m/s, and 4.5 m/s wearing standard neutral shoes. RESULTS: A dataset
comprising raw and processed kinematics and kinetics signals pertaining to this
experiment is available in various file formats. In addition, a file of metadata,
including demographics, running characteristics, foot-strike patterns, and muscle
strength and flexibility measurements is provided. Overall, there was an effect
of running speed on most of the gait-biomechanics variables selected for this
study. However, the foot-strike patterns were not affected by running speed.
DISCUSSION: Several applications of this dataset can be anticipated, including
testing new methods of data reduction and variable selection; for educational
purposes; and answering specific research questions. This last application was
exemplified in the study's second objective.
PMID- 28503380
TI - Student evaluations of teaching: teaching quantitative courses can be hazardous
to one's career.
AB - Anonymous student evaluations of teaching (SETs) are used by colleges and
universities to measure teaching effectiveness and to make decisions about
faculty hiring, firing, re-appointment, promotion, tenure, and merit pay.
Although numerous studies have found that SETs correlate with various teaching
effectiveness irrelevant factors (TEIFs) such as subject, class size, and grading
standards, it has been argued that such correlations are small and do not
undermine the validity of SETs as measures of professors' teaching effectiveness.
However, previous research has generally used inappropriate parametric statistics
and effect sizes to examine and to evaluate the significance of TEIFs on
personnel decisions. Accordingly, we examined the influence of quantitative vs.
non-quantitative courses on SET ratings and SET based personnel decisions using
14,872 publicly posted class evaluations where each evaluation represents a
summary of SET ratings provided by individual students responding in each class.
In total, 325,538 individual student evaluations from a US mid-size university
contributed to theses class evaluations. The results demonstrate that class
subject (math vs. English) is strongly associated with SET ratings, has a
substantial impact on professors being labeled satisfactory vs. unsatisfactory
and excellent vs. non-excellent, and the impact varies substantially depending on
the criteria used to classify professors as satisfactory vs. unsatisfactory.
Professors teaching quantitative courses are far more likely not to receive
tenure, promotion, and/or merit pay when their performance is evaluated against
common standards.
PMID- 28503381
TI - A survey of fishes associated with Hawaiian deep-water Halimeda kanaloana
(Bryopsidales: Halimedaceae) and Avrainvillea sp. (Bryopsidales: Udoteaceae)
meadows.
AB - The invasive macroalgal species Avrainvillea sp. and native species Halimeda
kanaloana form expansive meadows that extend to depths of 80 m or more in the
waters off of O'ahu and Maui, respectively. Despite their wide depth
distribution, comparatively little is known about the biota associated with these
macroalgal species. Our primary goals were to provide baseline information on the
fish fauna associated with these deep-water macroalgal meadows and to compare the
abundance and diversity of fishes between the meadow interior and sandy
perimeters. Because both species form structurally complex three-dimensional
canopies, we hypothesized that they would support a greater abundance and
diversity of fishes when compared to surrounding sandy areas. We surveyed the
fish fauna associated with these meadows using visual surveys and collections
made with clove-oil anesthetic. Using these techniques, we recorded a total of 49
species from 25 families for H. kanaloana meadows and surrounding sandy areas,
and 28 species from 19 families for Avrainvillea sp. habitats. Percent endemism
was 28.6% and 10.7%, respectively. Wrasses (Family Labridae) were the most
speciose taxon in both habitats (11 and six species, respectively), followed by
gobies for H. kanaloana (six species). The wrasse Oxycheilinus bimaculatus and
cardinalfish Apogonichthys perdix were the most frequently-occurring species
within the H. kanaloana and Avrainvillea canopies, respectively. Obligate
herbivores and food-fish species were rare in both habitats. Surprisingly, the
density and abundance of small epibenthic fishes were greater in open sand than
in the meadow canopy. In addition, species richness was also higher in open sand
for Avrainvillea sp. We hypothesize that the dense holdfasts and rhizoids present
within the meadow canopy may impede benthic-dwelling or bioturbator species,
which accounted for 86% and 57% of individuals collected in sand adjacent to H.
kanaloana and Avrainvillea sp. habitats, respectively. Of the 65 unique species
recorded in this study, 16 (25%) were detected in clove oil stations alone,
illustrating the utility of clove-oil anesthetic in assessing the diversity and
abundance of small-bodied epibenthic fishes.
PMID- 28503383
TI - Social relationships enhance the time spent eating and intake of a novel diet in
pregnant Hanwoo (Bos taurus coreanae) heifers.
AB - The objective of this study was to evaluate the effects of social relationships
on the feed intake, eating behavior, and growth, upon exposure to a novel diet,
in Hanwoo (Bos taurus coreanae) heifers during pregnancy. Twenty-four pregnant
Hanwoo heifers, averaging 438 +/- 27.8 kg in weight, 21 months in age, and 194 +/
8.5 days in pregnancy, were involved in a two-month (eight weeks) experiment.
The heifers were randomly assigned to either the single housing group (SG; one
individual per pen, n = 12), or the paired housing group (PG; two individuals per
pen, n = 12). All pens were of the same size (5 * 5 m) and provided with one feed
bin, which automatically recorded the individual feed intake and eating behavior.
As the experiment began, the diet of the heifers was switched from a total mixed
ration (TMR; 250 g/kg ryegrass straw and 750 g/kg concentrate mix) to a forage
only diet (mixed hay cubes composed of 500 g/kg alfalfa, 250 g/kg timothy, and
250 g/kg blue grass hay). The heifers were fed ad libitum twice a day. The
individual feed intake and eating behavior were recorded daily throughout the
experiment, and body weights (BWs) were measured every four weeks before the
morning feeding. PG animals visited the feed bin 22% less often than SG. PG,
however, stayed 39% longer in the feed bin and consumed 40% more feed per visit,
compared with SG. Consequently, PG heifers spent 23% more time in eating and had
16% more daily dry matter intake than SG during the experiment. Average daily
gain during the experimental period tended to be greater in PG than in SG. When
pregnant Hanwoo heifers encountered a novel diet, social relationships (i.e.,
presence of a pen-mate) enhanced their time spent eating and feed intake. Social
interactions, even with an unfamiliar individual, may be helpful for pregnant
Hanwoo heifers cope with a diet challenge compared to solitary situation.
PMID- 28503382
TI - Poly(ADP-ribosylation) is present in murine sciatic nerve fibers and is altered
in a Charcot-Marie-Tooth-1E neurodegenerative model.
AB - BACKGROUND: Poly-ADP-ribose (PAR) is a polymer synthesized by poly-ADP-ribose
polymerases (PARPs) as a postranslational protein modification and catabolized
mainly by poly-ADP-ribose glycohydrolase (PARG). In spite of the existence of
cytoplasmic PARPs and PARG, research has been focused on nuclear PARPs and PAR,
demonstrating roles in the maintenance of chromatin architecture and the
participation in DNA damage responses and transcriptional regulation. We have
recently detected non-nuclear PAR structurally and functionally associated to the
E-cadherin rich zonula adherens and the actin cytoskeleton of VERO epithelial
cells. Myelinating Schwann cells (SC) are stabilized by E-cadherin rich autotypic
adherens junctions (AJ). We wondered whether PAR would map to these regions.
Besides, we have demonstrated an altered microfilament pattern in peripheral
nerves of Trembler-J (Tr-J) model of CMT1-E. We hypothesized that cytoplasmic PAR
would accompany such modified F-actin pattern. METHODS: Wild-type (WT) and Tr-J
mice sciatic nerves cryosections were subjected to immunohistofluorescence with
anti-PAR antibodies (including antibody validation), F-actin detection with a
phalloidin probe and DAPI/DNA counterstaining. Confocal image stacks were
subjected to a colocalization highlighter and to semi-quantitative image
analysis. RESULTS: We have shown for the first time the presence of PAR in
sciatic nerves. Cytoplasmic PAR colocalized with F-actin at non-compact myelin
regions in WT nerves. Moreover, in Tr-J, cytoplasmic PAR was augmented in close
correlation with actin. In addition, nuclear PAR was detected in WT SC and was
moderately increased in Tr-J SC. DISCUSSION: The presence of PAR associated to
non-compact myelin regions (which constitute E-cadherin rich autotypic AJ/actin
anchorage regions) and the co-alterations experienced by PAR and the actin
cytoskeleton in epithelium and nerves, suggest that PAR may be a constitutive
component of AJ/actin anchorage regions. Is PAR stabilizing the AJ-actin
complexes? This question has strong implications in structural cell biology and
cell signaling networks. Moreover, if PAR played a stabilizing role, such
stabilization could participate in the physiological control of axonal branching.
PARP and PAR alterations exist in several neurodegenerative pathologies including
Alzheimer's, Parkinson's and Hungtington's diseases. Conversely, PARP inhibition
decreases PAR and promotes neurite outgrowth in cortical neurons in vitro.
Coherently, the PARP inhibitor XAV939 improves myelination in vitro, ex vivo and
in vivo. Until now such results have been interpreted in terms of nuclear PARP
activity. Our results indicate for the first time the presence of PARylation in
peripheral nerve fibers, in a healthy environment. Besides, we have evidenced a
PARylation increase in Tr-J, suggesting that the involvement of cytoplasmic PARPs
and PARylation in normal and neurodegenerative conditions should be re-evaluated.
PMID- 28503384
TI - Divergent effect of fluoxetine on the response to physical or chemical stressors
in zebrafish.
AB - Fluoxetine is a selective serotonin reuptake inhibitor that increases serotonin
concentration in the central nervous system and modulates various systems,
including the control of sympathetic outflow and the hypothalamus-pituitary
adrenal. However, it is not yet established whether fluoxetine can modulate the
responses to stressors stimulants (physical or chemical) that trigger cortisol
response in zebrafish. We demonstrate that fluoxetine blunts the response to
physical stress, but not to chemical stress.
PMID- 28503386
TI - Mechanical Thrombectomy for Acute Ischemic Stroke After Cardiac Surgery.
AB - Ischemic stroke is a rare yet devastating complication that may occur following
cardiothoracic surgery. Fibrinolytic treatment is contraindicated due to elevated
risk for hemorrhage. Mechanical thrombectomy entails a catheterized approach
wherein the thrombus is physically removed from the vessel without the use of
fibrinolytics, minimizing the possibility of intracranial hemorrhage. Here, we
present two original cases of mechanical thrombectomy as treatment for patients
experiencing emergent large vessel occlusion following cardiothoracic surgery. A
literature review was conducted to determine current treatment guidelines, risk
factors, and complications resulting from recanalization due to mechanical
thrombectomy versus fibrinolytic therapy. One patient was admitted due to
chronic, American College of Cardiology/American Heart Association stage D, New
York Heart Association functional class IV heart failure and required complete,
artificial hemodynamic support for two weeks and on the 19th day experienced
neurologic decline secondary to a supraclinoid left internal carotid artery (ICA)
occlusion. Mechanical thrombectomy resulted in distal reperfusion and neurologic
improvement. The second patient presented with coronary artery disease and
underwent triple coronary artery bypass grafting and endovein harvesting. On post
operative day 2, the patient experienced a left ICA occlusion extending to the
cavernous ICA resulting in speech impairment and right-sided weakness. The
patient was heparinized and underwent mechanical thrombectomy, resulting in
immediate speech and muscle strength recovery. Medical advances allow mechanical
thrombectomy to be performed in a timely and effective manner at specialized
treatment centers. It offers endovascular treatment modalities to a unique
patient population with postoperative stroke. In such patients, thrombectomy can
safely provide reperfusion while reducing the risk of complications associated
with conventional thrombolytics.
PMID- 28503385
TI - Intervention effects of five cations and their correction on hemolytic activity
of tentacle extract from the jellyfish Cyanea capillata.
AB - Cations have generally been reported to prevent jellyfish venom-induced hemolysis
through multiple mechanisms by spectrophotometry. Little attention has been paid
to the potential interaction between cations and hemoglobin, potentially
influencing the antagonistic effect of cations. Here, we explored the effects of
five reported cations, La3+, Mn2+, Zn2+, Cu2+ and Fe2+, on a hemolytic test
system and the absorbance of hemoglobin, which was further used to measure their
effects on the hemolysis of tentacle extract (TE) from the jellyfish Cyanea
capillata. All the cations displayed significant dose-dependent inhibitory
effects on TE-induced hemolysis with various dissociation equilibrium constant
(Kd) values as follows: La3+ 1.5 mM, Mn2+ 93.2 mM, Zn2+ 38.6 mM, Cu2+ 71.9 MUM
and Fe2+ 32.8 mM. The transparent non-selective pore blocker La3+ did not affect
the absorbance of hemoglobin, while Mn2+ reduced it slightly. Other cations,
including Zn2+, Cu2+ and Fe2+, greatly decreased the absorbance with Kd values of
35.9, 77.5 and 17.6 mM, respectively. After correction, the inhibitory Kd values
were 1.4 mM, 45.8 mM, 128.5 MUM and 53.1 mM for La3+, Zn2+, Cu2+ and Fe2+,
respectively. Mn2+ did not inhibit TE-induced hemolysis. Moreover, the inhibitory
extent at the maximal given dose of all cations except La3+ was also diminished.
These corrected results from spectrophotometry were further confirmed by direct
erythrocyte counting under microscopy. Our results indicate that the cations,
except for La3+, can interfere with the absorbance of hemoglobin, which should be
corrected when their inhibitory effects on hemolysis by jellyfish venoms are
examined. The variation in the inhibitory effects of cations suggests that the
hemolysis by jellyfish venom is mainly attributed to the formation of non
selective cation pore complexes over other potential mechanisms, such as
phospholipases A2 (PLA2), polypeptides, protease and oxidation. Blocking the pore
forming complexes may be a primary strategy to improve the in vivo damage and
mortality from jellyfish stings due to hemolytic toxicity.
PMID- 28503387
TI - Rubinstein-Taybi Syndrome Associated with Pituitary Macroadenoma: A Case Report.
AB - Rubinstein-Taybi Syndrome (RSTS) is an autosomal dominant disorder that is
classically characterized by prenatal and postnatal growth restriction,
microcephaly, dysmorphic craniofacial features, broad thumbs and toes, and
intellectual disability. We describe the first reported case of a pituitary
macroadenoma associated with RSTS. A 39-year-old Caucasian female with a past
medical history of RSTS diagnosed at age two was found to have a gadolinium
enhancing pituitary mass on magnetic resonance imaging (MRI) of the brain three
years ago during workup for migraine-like headaches. Subsequent serial imaging
showed radiographic evidence of growth up to 11.5 x 14.0 x 10.0 mm in size. The
pituitary sellar lesion was resected through an endoscopic transnasal
transsphenoidal approach and was found to be a thyrotroph adenoma. RSTS is a
rare, neurodevelopmental genetic disease where most patients with disabilities
survive into adulthood. The disorder is associated with an increased
predisposition for development of nervous system tumors, including pituitary
adenomas.
PMID- 28503388
TI - Pilot Study of 99mTc-labeled Ethylene Dicysteine Deoxyglucose SPECT-CT Imaging in
Treatment Response Evaluation in Patients with Locally Advanced Head and Neck
Cancer.
AB - BACKGROUND: The purpose of this study is to describe the preliminary findings of
99mTc-labeled ethylene dicysteine deoxyglucose (99mTc-EC-DG) performed four weeks
after chemoradiotherapy in patients with locally advanced head and neck squamous
cell carcinoma. METHODS: Review of nine patients with locally advanced head and
neck squamous cell carcinomas imaged with 99mTc-EC-DG single photon emission
computed tomography-computed tomography (SPECT-CT) at baseline before treatment
and at four weeks after treatment completion was performed. RESULTS: At four
weeks post-treatment, five patients had either decreased activity or no
significant activity on 99mTc-EC-DG SPECT-CT and were considered to have
responded to treatment, whereas four patients did not have significantly
decreased uptake on 99mTc-EC-DG SPECT-CT and were considered to have not
adequately responded to treatment. Among the five patients considered to have
treatment response at four weeks, all were free of disease (true-negative). Among
the four patients considered to have stable activity on 99mTc-EC-DG SPECT-CT at
four weeks, two were designated as having no response or incomplete response
(true-positive), and two were designated as having complete response (false
positive) on subsequent composite assessment. CONCLUSIONS: The pilot data is
promising but warrants further investigation of 99mTc-EC-DG SPECT-CT for the
assessment of locoregional treatment response at four weeks in patients with
locally advanced head and neck squamous cell carcinomas.
PMID- 28503389
TI - Rosai-Dorfman Disease of the Breast.
AB - Rosai-Dorfman disease (also known as sinus histiocytosis with massive
lymphadenopathy) is a rare benign proliferative disorder of histiocytes that
typically involves the lymph nodes and can also involve extranodal sites. Rosai
Dorfman disease confined to the breast is extremely rare, but important to
recognize as it can mimic malignancy. We present the case of a 63-year-old woman
who presented with a palpable breast lump that was highly suspicious for
malignancy based on mammogram and ultrasound appearance. Biopsy revealed
inflammatory tissue with lymphoplasmacytic and histiocytic predominance. The
diagnosis of Rosai-Dorfman was made based on characteristic staining of
histiocytes with S-100 and the presence of emperipolesis. Early recognition of
this benign disease entity spared the patient further investigation and surgical
intervention.
PMID- 28503390
TI - The Challenges of Developing a Participatory Arts Intervention for Caregivers of
Persons with Dementia.
AB - OBJECTIVE: We describe the development and challenges in implementing a web-based
participatory art intervention specifically designed for caregivers of persons
with dementia to use at home with their loved one. Method: An interprofessional
team, including an experienced national panel of artists, developed a
participatory arts toolkit consisting of seven web-based modules involving a
combination of music, singing, dancing, poetry, and painting. Participants
completed a survey of demographics, caregiver needs, and caregiver burden.
Results: Thirty caregivers with high caregiver needs and a high caregiver burden
volunteered to pilot the intervention. Difficulties with caregiver recruitment
and compliance with lesson plans were noted. Caregivers provided positive and
negative qualitative feedback. Discussion: The challenges and possible
solutions to the problems identified in the implementation and assessment of this
participatory arts intervention will provide important insights for future
studies linking the arts and dementia care.
PMID- 28503391
TI - Prevalence and Predictors of Use of Home Sphygmomanometers Among Hypertensive
Patients.
AB - OBJECTIVE: Few studies have looked at the predictors of use of home
sphygmomanometers among hypertensive patients in low-income countries such as
Pakistan. Considering the importance of home blood pressure monitoring (HBPM),
cross-sectional study was conducted to evaluate the prevalence and predictors of
the usage of all kinds of HBPM devices. METHOD: This study was conducted in
Karachi during the time period of January-February 2017. Adult patients
previously diagnosed with hypertension visiting tertiary care hospitals were
selected for the study. Interviews from the individuals were conducted after
verbal consent using a pre-coded questionnaire. The data was analyzed using
Statistical Package for the Social Sciences v. 23.0 (SPSS, IBM Corporation, NY,
USA). Chi-squared test was applied as the primary statistical test. RESULTS: More
than half of the participants used a home sphygmomanometer (n=250, 61.7%). The
age, level of education, family history of hypertension, compliance to drugs and
blood pressure (BP) monitoring, few times a month at clinics were significant
determinants of HBPM (P values < 0.001). It was found that more individuals owned
a digital sphygmomanometer (n=128, 51.3%) as compared to a manual type (n=122,
48.8%). Moreover, avoiding BP measurement in a noisy environment was the most
common precaution taken (n=117, 46.8%). CONCLUSION: The study showed that around
40% of the hypertensive individuals did not own a sphygmomanometer and less than
25% performed HBPM regularly. General awareness by healthcare professionals can
be a possible factor which can increase HBPM.
PMID- 28503392
TI - Heritability of Hippocampal Formation Sub-region Volumes.
AB - BACKGROUND: Hippocampal formation (HF) volume and episodic memory performance are
substantially heritable, but HF subregion heritability estimates and their
possible shared genetic variance with episodic memory performance remain to be
determined. METHODS AND FINDINGS: This study provides heritability estimates for
hippocampal subregions (e.g, Cornu Amonis, Subiculum, Parasubiculum, Molecular
and Granule Cell Layers of the Dentate Gryus) and Total HF volumes obtained using
FreeSurfer 6.0. In addition, this study assesses the heritability of object
sequence and verbal episodic memory performance, and the amount of shared genetic
variance between HF subregions and Total HF volume and episodic memory
performance. HF volumes were obtained from high-resolution brain scans from a
sample of 499 siblings (mean age+/-SD=30.0+/-3.1, 203 men), including 51
monozygotic and 46 dizygotic twin pairs and 305 non-twin siblings, collected by
the Human Connectome Project (www.humanconnectome.org). Heritability estimates
for HF subregions ranged from 0.42-0.87 and shared genetic variance of HF
subregions with hippocampal volume was substantial (mean=0.79, range=0.50-0.98).
HF subregion volumes residualized for Total HF and percent HF subregion volumes
were also found to be substantially heritable (range=0.04-0.86 and 0.07-0.84,
respectively). Verbal (h2=0.47) but not object sequence episodic memory was found
to be significantly heritable; though the amount of shared genetic variance
between HF subregions and verbal episodic memory was low (mean=0.10, range=0.01
0.20). CONCLUSIONS: These findings suggest that HF subregion volumes are
heritable and can be used as quantitative phenotypes in genetic association
studies. The low shared genetic variance between HF subregions and verbal
episodic memory suggests that quantitative trait analyses may not benefit from
including both HF volume and episodic memory as bivariate traits in healthy
individuals. The extent to which HF subregion volumes share genetic variance with
neuropsychiatric disorders, and as such add value to our ability to identify
genetic risk loci for these disorders, remains to be determined.
PMID- 28503393
TI - Measuring adhesion on rough surfaces using atomic force microscopy with a liquid
probe.
AB - We present a procedure to perform and interpret pull-off force measurements
during the jump-off-contact process between a liquid drop and rough surfaces
using a conventional atomic force microscope. In this method, a micrometric
liquid mercury drop is attached to an AFM tipless cantilever to measure the force
required to pull this drop off a rough surface. We test the method with two
surfaces: a square array of nanometer-sized peaks commonly used for the
determination of AFM tip sharpness and a multi-scaled rough diamond surface
containing sub-micrometer protrusions. Measurements are carried out in a nitrogen
atmosphere to avoid water capillary interactions. We obtain information about the
average force of adhesion between a single peak or protrusion and the liquid
drop. This procedure could provide useful microscopic information to improve our
understanding of wetting phenomena on rough surfaces.
PMID- 28503395
TI - The role of 2D/3D spin-polarization interactions in hybrid copper hydroxide
acetate: new insights from first-principles molecular dynamics.
AB - The magnetic properties response of the layered hybrid material copper hydroxide
acetate Cu2(OH)3CH3COO.H2O is studied as a function of the applied pressure
within first-principles molecular dynamics. We are able to elucidate the
interplay between the structural properties of this material and its magnetic
character, both at the local (atomic) level and at the bulk level. We performed a
detailed analysis of the intralayer spin configurations occurring for each value
of the imposed projection along the z-axis for the total spin and of the applied
pressure. The transition from an antiferromagnetic to a ferromagnetic state at
high pressure (above 3 GPa) goes along with a vanishing difference between the
spin polarizations pertaining to each layer. Therefore, at high pressure, copper
hydroxide acetate is a ferromagnet with no changes of spin polarization in the
direction perpendicular to the inorganic layers.
PMID- 28503396
TI - Hybrid nanomaterials: from the laboratory to the market.
PMID- 28503394
TI - Investigation of growth dynamics of carbon nanotubes.
AB - The synthesis of single-walled carbon nanotubes (SWCNTs) with defined properties
is required for both fundamental investigations and practical applications. The
revealing and thorough understanding of the growth mechanism of SWCNTs is the key
to the synthesis of nanotubes with required properties. This paper reviews the
current status of the research on the investigation of growth dynamics of carbon
nanotubes. The review starts with the consideration of the peculiarities of the
growth mechanism of carbon nanotubes. The physical and chemical states of the
catalyst during the nanotube growth are discussed. The chirality selective growth
of nanotubes is described. The main part of the review is dedicated to the
analysis and systematization of the reported results on the investigation of
growth dynamics of nanotubes. The studies on the revealing of the dependence of
the growth rate of nanotubes on the synthesis parameters are reviewed. The
correlation between the lifetime of catalyst and growth rate of nanotubes is
discussed. The reports on the calculation of the activation energy of the
nanotube growth are summarized. Finally, the growth properties of inner tubes
inside SWCNTs are considered.
PMID- 28503397
TI - Relationships between chemical structure, mechanical properties and materials
processing in nanopatterned organosilicate fins.
AB - The exploitation of nanoscale size effects to create new nanostructured materials
necessitates the development of an understanding of relationships between
molecular structure, physical properties and material processing at the
nanoscale. Numerous metrologies capable of thermal, mechanical, and electrical
characterization at the nanoscale have been demonstrated over the past two
decades. However, the ability to perform nanoscale molecular/chemical structure
characterization has only been recently demonstrated with the advent of atomic
force-microscopy-based infrared spectroscopy (AFM-IR) and related techniques.
Therefore, we have combined measurements of chemical structures with AFM-IR and
of mechanical properties with contact resonance AFM (CR-AFM) to investigate the
fabrication of 20-500 nm wide fin structures in a nanoporous organosilicate
material. We show that by combining these two techniques, one can clearly observe
variations of chemical structure and mechanical properties that correlate with
the fabrication process and the feature size of the organosilicate fins.
Specifically, we have observed an inverse correlation between the concentration
of terminal organic groups and the stiffness of nanopatterned organosilicate
fins. The selective removal of the organic component during etching results in a
stiffness increase and reinsertion via chemical silylation results in a stiffness
decrease. Examination of this effect as a function of fin width indicates that
the loss of terminal organic groups and stiffness increase occur primarily at the
exposed surfaces of the fins over a length scale of 10-20 nm. While the observed
structure-property relationships are specific to organosilicates, we believe the
combined demonstration of AFM-IR with CR-AFM should pave the way for a similar
nanoscale characterization of other materials where the understanding of such
relationships is essential.
PMID- 28503398
TI - Synthesis of coaxial nanotubes of polyaniline and poly(hydroxyethyl methacrylate)
by oxidative/initiated chemical vapor deposition.
AB - Vapor-phase synthesis techniques of polymeric nanostructures offer unique
advantages over conventional, solution-based techniques because of their
solventless nature. In this work, we report the fabrication of coaxial polymer
nanotubes using two different chemical vapor deposition methods. The fabrication
process involves the deposition of an outer layer of the conductive polyaniline
(PANI) by oxidative chemical vapor deposition, followed by the deposition of the
inner layer of poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogel by initiated
chemical vapor deposition. The vapor-phase techniques allowed for fine-tuning of
the thickness of the individual layers, keeping the functionalities of the
polymers intact. The response of the single components and the coaxial nanotubes
to changes in humidity was investigated for potential humidity sensor
applications. For single-component conductive PANI nanotubes, the resistance
changed parabolically with relative humidity because of competing effects of
doping and swelling of the PANI polymer under humid conditions. Introducing a
hydrogel inner layer increased the overall resistance, and enhanced swelling,
which caused the resistance to continuously increase with relative humidity.
PMID- 28503399
TI - Functional dependence of resonant harmonics on nanomechanical parameters in
dynamic mode atomic force microscopy.
AB - We present a combined theoretical and experimental study of the dependence of
resonant higher harmonics of rectangular cantilevers of an atomic force
microscope (AFM) as a function of relevant parameters such as the cantilever
force constant, tip radius and free oscillation amplitude as well as the
stiffness of the sample's surface. The simulations reveal a universal functional
dependence of the amplitude of the 6th harmonic (in resonance with the 2nd
flexural mode) on these parameters, which can be expressed in terms of a gun
shaped function. This analytical expression can be regarded as a practical tool
for extracting qualitative information from AFM measurements and it can be
extended to any resonant harmonics. The experiments confirm the predicted
dependence in the explored 3-45 N/m force constant range and 2-345 GPa sample's
stiffness range. For force constants around 25 N/m, the amplitude of the 6th
harmonic exhibits the largest sensitivity for ultrasharp tips (tip radius below
10 nm) and polymers (Young's modulus below 20 GPa).
PMID- 28503400
TI - Triptycene-terminated thiolate and selenolate monolayers on Au(111).
AB - To study the implications of highly space-demanding organic moieties on the
properties of self-assembled monolayers (SAMs), triptycyl thiolates and
selenolates with and without methylene spacers on Au(111) surfaces were
comprehensively studied using ultra-high vacuum infrared reflection absorption
spectroscopy, X-ray photoelectron spectroscopy, near-edge X-ray absorption fine
structure spectroscopy and thermal desorption spectroscopy. Due to packing
effects, the molecules in all monolayers are substantially tilted. In the
presence of a methylene spacer the tilt is slightly less pronounced. The
selenolate monolayers exhibit smaller defect densities and therefore are more
densely packed than their thiolate analogues. The Se-Au binding energy in the
investigated SAMs was found to be higher than the S-Au binding energy.
PMID- 28503401
TI - Bio-inspired micro-to-nanoporous polymers with tunable stiffness.
AB - Background: Inspired by structural hierarchies and the related excellent
mechanical properties of biological materials, we created a smoothly graded micro
to nanoporous structure from a thermoplastic polymer. Results: The viscoelastic
properties for the different pore sizes were investigated in the glassy regime by
dynamic flat-punch indentation. Interestingly, the storage modulus was observed
to increase with increasing pore-area fraction. Conclusion: This outcome appears
counterintuitive at first sight, but can be rationalized by an increase of the
pore wall thickness as determined by our quantitative analysis of the pore
structure. Therefore, our approach represents a non-chemical way to tune the
elastic properties and their local variation for a broad range of polymers by
adjusting the pore size gradient.
PMID- 28503403
TI - Diagnostics in Hymenoptera venom allergy: current concepts and developments with
special focus on molecular allergy diagnostics.
AB - BACKGROUND: The high rate of asymptomatic sensitization to Hymenoptera venom,
difficulty in correctly identifying Hymenoptera and loss of sensitization over
time make an accurate diagnosis of Hymenoptera venom allergy challenging.
Although routine diagnostic tests encompassing skin tests and the detection of
venom-specific IgE antibodies with whole venom preparations are reliable, they
offer insufficient precision in the case of double sensitized patients or in
those with a history of sting anaphylaxis, in whom sensitization cannot be proven
or only to the presumably wrong venom. METHODS: Systematic literature research
and review of current concepts of diagnostic testing in Hymenoptera venom
allergy. RESULTS AND DISCUSSION: Improvements in diagnostic accuracy over recent
years have mainly been due to the increasing use of molecular allergy
diagnostics. Detection of specific IgE antibodies to marker and cross-reactive
venom allergens improves the discrimination between genuine sensitization and
cross-reactivity, and this provides a better rationale for prescribing venom
immunotherapy. The basophil activation test has also increased diagnostic
accuracy by reducing the number of Hymenoptera venom sensitizations overlooked
with routine tests. This paper reviews current concepts of diagnostic testing in
Hymenoptera venom allergy and suggests fields for further development.
PMID- 28503402
TI - Physical Exercise for Treatment of Mood Disorders: A Critical Review.
AB - PURPOSE OF THE REVIEW: The purpose of this review is to critically assess the
evidence for exercise as an adjunct intervention for major depressive disorder
and bipolar disorder, chronic conditions characterized by frequent comorbid
conditions as well as interepisodic symptoms with poor quality of life and
impaired functioning. Individuals with these mood disorders are at higher risk of
cardiovascular disease and premature death in part because of increased rates of
obesity, inactivity, and diabetes mellitus compared to the general population.
Exercise may not only mitigate the increased risk of cardiovascular disease, but
could also potentially improve the long term outcomes of mood disorders. RECENT
FINDINGS: We conducted a literature review on the impact of exercise on mood
disorders and associated comorbid conditions as well as possible biological
mechanisms. We found that exercise impacts both the physical health parameters of
mood disorders as well as mental health outcomes. Exercise also positively
impacts conditions frequently comorbid with mood disorders (i.e. anxiety, pain,
and insomnia). There are multiple candidate biomarkers for exercise, with brain
derived neurotrophic factor and oxidative stress as two main promising components
of exercise's anti-depressant effect. SUMMARY: Exercise appears to be a promising
adjunct treatment for mood disorders. We conclude with recommendations for future
research of exercise as an adjunct intervention for mood disorders.
PMID- 28503405
TI - Nanoparticle Design Strategies for Effective Cancer Immunotherapy.
AB - Cancer immunotherapy is a rapidly evolving and paradigm shifting treatment
modality that adds a strong tool to the collective cancer treatment arsenal. It
can be effective even for late stage diagnoses and has already received clinical
approval. Tumors are known to not only avoid immune surveillance but also exploit
the immune system to continue local tumor growth and metastasis. Because of this,
most immunotherapies, particularly those directed against solid cancers, have
thus far only benefited a small minority of patients. Early clinical
substantiation lends weight to the claim that cancer immunotherapies, which are
adaptive and enduring treatment methods, generate much more sustained and robust
anticancer effects when they are effectively formulated in nanoparticles or
scaffolds than when they are administered as free drugs. Engineering cancer
immunotherapies using nanomaterials is, therefore, a very promising area worthy
of further consideration and investigation. This review focuses on the recent
advances in cancer immunoengineering using nanoparticles for enhancing the
therapeutic efficacy of a diverse range of immunotherapies. The delivery of
immunostimulatory agents to antitumor immune cells, such as dendritic or antigen
presenting cells, may be a far more efficient tactic to eradicate tumors than
delivery of conventional chemotherapeutic and cytotoxic drugs to cancer cells. In
addition to its immense therapeutic potential, immunoengineering using
nanoparticles also provides a valuable tool for unearthing and understanding the
basics of tumor biology. Recent research using nanoparticles for cancer
immunotherapy has demonstrated the advantage of physicochemical manipulation in
improving the delivery of immunostimulatory agents. In vivo studies have tested a
range of particle sizes, mostly less than 300 nm, and particles with both
positive and negative zeta potentials for various applications. Material
composition and surface modifications have been shown to contribute significantly
in selective targeting, efficient delivery and active stimulation of immune
system targets. Thus, these investigations, including a wide array of
nanoparticles for cancer immunotherapy, substantiate the employment of
nanocarriers for efficacious cancer immunotherapies.
PMID- 28503407
TI - Potential in vitro model for testing the effect of exposure to nanoparticles on
the lung alveolar epithelial barrier.
AB - Pulmonary barrier function plays a pivotal role in protection from inhaled
particles. However, some nano-scaled particles, such as carbon nanotubes (CNT),
have demonstrated the ability to penetrate this barrier in animal models,
resulting in an unusual, rapid interstitial fibrosis. To delineate the underlying
mechanism and specific bio-effect of inhaled nanoparticles in respiratory
toxicity, models of lung epithelial barriers are required that allow accurate
representation of in vivo systems; however, there is currently a lack of
consistent methods to do so. Thus, this work demonstrates a well-characterized in
vitro model of pulmonary barrier function using Calu-3 cells, and provides the
experimental conditions required for achieving tight junction complexes in cell
culture, with trans-epithelial electrical resistance measurement used as a
biosensor for proper barrier formation and integrity. The effects of cell number
and serum constituents have been examined and we found that changes in each of
these parameters can greatly affect barrier formation. Our data demonstrate that
use of 5.0 * 104 Calu-3 cells/well in the Transwell cell culture system, with 10%
serum concentrations in culture media is optimal for assessing epithelial barrier
function. In addition, we have utilized CNT exposure to analyze the dose-, time-,
and nanoparticle property-dependent alterations of epithelial barrier
permeability as a means to validate this model. Such high throughput in vitro
cell models of the epithelium could be used to predict the interaction of other
nanoparticles with lung epithelial barriers to mimic respiratory behavior in
vivo, thus providing essential tools and bio-sensing techniques that can be
uniformly employed.
PMID- 28503404
TI - Wnt Signaling in Normal and Malignant Stem Cells.
AB - Wnt signaling plays important roles in stem cell self-renewal and differentiation
in adults as well as in embryonic development. Mutations that activate canonical
Wnt/beta-catenin signaling also initiate and maintain several cancer states,
including colorectal cancer and leukemia, and hence Wnt inhibitors are currently
being explored as therapeutic options. In this review, we summarize previous
studies and update recent findings on canonical Wnt signaling and its components,
as well as their roles in somatic stem cell homeostasis and maintenance of cancer
initiating cells.
PMID- 28503408
TI - Trifluoperazine inhibits acetaminophen-induced hepatotoxicity and hepatic
reactive nitrogen formation in mice and in freshly isolated hepatocytes.
AB - The hepatotoxicity of acetaminophen (APAP) occurs by initial metabolism to N
acetyl-p-benzoquinone imine which depletes GSH and forms APAP-protein adducts.
Subsequently, the reactive nitrogen species peroxynitrite is formed from nitric
oxide (NO) and superoxide leading to 3-nitrotyrosine in proteins. Toxicity occurs
with inhibited mitochondrial function. We previously reported that in hepatocytes
the nNOS (NOS1) inhibitor NANT inhibited APAP toxicity, reactive nitrogen and
oxygen species formation, and mitochondrial dysfunction. In this work we examined
the effect of trifluoperazine (TFP), a calmodulin antagonist that inhibits
calcium induced nNOS activation, on APAP hepatotoxicity and reactive nitrogen
formation in murine hepatocytes and in vivo. In freshly isolated hepatocytes TFP
inhibited APAP induced toxicity, reactive nitrogen formation (NO, GSNO, and 3
nitrotyrosine in protein), reactive oxygen formation (superoxide), loss of
mitochondrial membrane potential, decreased ATP production, decreased oxygen
consumption rate, and increased NADH accumulation. TFP did not alter APAP induced
GSH depletion in the hepatocytes or the formation of APAP protein adducts which
indicated that reactive metabolite formation was not inhibited. Since we
previously reported that TFP inhibits the hepatotoxicity of APAP in mice without
altering hepatic APAP-protein adduct formation, we examined the APAP treated
mouse livers for evidence of reactive nitrogen formation. 3-Nitrotyrosine in
hepatic proteins and GSNO were significantly increased in APAP treated mouse
livers and decreased in the livers of mice treated with APAP plus TFP. These data
are consistent with a hypothesis that APAP hepatotoxicity occurs with altered
calcium metabolism, activation of nNOS leading to increased reactive nitrogen
formation, and mitochondrial dysfunction.
PMID- 28503409
TI - Taming immune suppressor: application of myeloid-derived suppressor cells in anti
cancer gene therapy.
PMID- 28503406
TI - Sleep in Neurodevelopmental Disorders.
AB - Individuals with intellectual and developmental disabilities (IDD) experience
sleep problems at higher rates than the general population. Although individuals
with IDD are a heterogeneous group, several sleep problems cluster within genetic
syndromes or disorders. This review summarizes the prevalence of sleep problems
experienced by individuals with Angelman syndrome, Cornelia de Lange syndrome,
Cri du Chat syndrome, Down syndrome, fragile X syndrome, Prader-Willi syndrome,
Smith-Magenis syndrome, Williams syndrome, autism spectrum disorder, and
idiopathic IDD. Factors associated with sleep problems and the evidence for sleep
treatments are reviewed for each neurodevelopmental disorder. Sleep research
advancements in neurodevelopmental disorders are reviewed, including the need for
consistency in defining and measuring sleep problems, considerations for research
design and reporting of results, and considerations when evaluating sleep
treatments.
PMID- 28503410
TI - The ideal substitute for tricuspid valve replacement in patients with congenital
heart disease: an unsolved dilemma.
PMID- 28503411
TI - Ascending aortic slide for interrupted aortic arch repair: a new approach to
maintain native tissue continuity.
PMID- 28503412
TI - Editorial on "vascular ring diagnosis and management: notable trends over 25
years".
PMID- 28503413
TI - The feeding conundrum.
PMID- 28503414
TI - Adult-onset deletion of the Prader-Willi syndrome susceptibility gene Snord116 in
mice results in reduced feeding and increased fat mass.
AB - BACKGROUND: The imprinted small nucleolar RNA (snoRNA) Snord116 is implicated in
the aetiology of Prader-Willi syndrome (PWS), a disease associated with
hyperphagia and obesity. Germline deletion of Snord116 in mice has been found to
lead to increased food intake but not to the development of obesity. To determine
the role of Snord116 independent of potential compensatory developmental factors,
we investigated the effects of conditional adult-onset deletion of Snord116 in
mice. METHODS: Deletion of Snord116 was induced at 8 weeks of age by oral
administration of tamoxifen to male Snordlox/lox; ROSAcre/+ mice, with vehicle
treated mice used as controls. Body weight (BW) was monitored weekly and body
composition was measured by dual-energy X-ray absorptiometry and tissue
dissection. Non-fasted and fasting-induced food intake was determined, and
glucose and insulin tolerance tests were performed. Twenty-four-hour energy
expenditure and physical activity were assessed by indirect calorimetry. RESULTS:
Adult-onset deletion of Snord116 led to reduced food intake and increased
adiposity, albeit with no concomitant change in BW or lean mass compared to
controls. Adult onset Snord116 deletion was also associated with worsened glucose
tolerance and insulin sensitivity. CONCLUSIONS: This study identified a key role
for Snord116 in feeding behaviour and growth. Further, it is likely that the
effects of this gene are modulated by developmental stage, as mice with adult
onset deletion showed an opposite phenotype, with respect to food intake and body
composition, to previously published data on mice with germline deletion.
PMID- 28503415
TI - Kickboxing power hour: case report of fifth metatarsal apophysitis (Iselin
disease) and its magnetic resonance imaging features.
AB - Youth now-a-days are getting more involved in mixed martial arts, with increasing
number of cases of lateral foot pain due to various causes. The differential
diagnoses of lateral foot pain in the pediatric population include avulsion
fracture of the fifth metatarsal base, Jones fracture, diaphyseal stress fracture
as well as os vesalianum pedis. We present a case of a 15-year-old athletic boy
who presented with left lateral foot pain for a few weeks. The patient was
actively involved in Kickboxing as well as active running. Left foot radiographs
were normal, including normal radiographic appearance of the fifth metatarsal
apophysis. Due to ongoing pain, magnetic resonance imaging of the left foot was
performed, which revealed apophysitis of the fifth metatarsal, known as Iselin
disease. Iselin disease has been postulated to be caused by traction on the fifth
metatarsal apophysis by performing sidekicks or round kicks during the kickboxing
practice. Iselin disease should be suspected in young children of 10-15 years age
involved in physical activity presenting with lateral foot pain. Magnetic
resonance imaging is extremely useful to correctly diagnose this condition and
avoid misdiagnosis of a fracture.
PMID- 28503416
TI - A case of Raoultella planticola causing a urinary tract infection in a pediatric
patient.
AB - Raoultella planticola (R. planticola) is an abundant environmental bacterium that
rarely infects humans. There is only one known case of R. planticola causing a
urinary tract infection (UTI) in a pediatric patient. This is a second case of R.
planticola potentially causing a symptomatic UTI in a 2-month-old female child
with no known medical problems.
PMID- 28503418
TI - Clown therapy: not only a pediatric matter.
PMID- 28503417
TI - Indoor/outdoor not-voluptuary-habit pollution and sleep-disordered breathing in
children: a systematic review.
AB - BACKGROUND: Exposure to environmental pollutants is advocated to be a major risk
factor, with increased morbidity and mortality in humans due to acute and chronic
airway inflammation. The aim of the present review is to show the literature
research regarding the link between the sleep-disordered breathing and exposure
to indoor/outdoor pollution in children. We hypothesized that environmental air
pollution can play a role in childhood sleep-disordered breathing. METHODS: We
conducted an electronic search in Medline (with PubMed interface), Scopus and the
ISI Web of Science using the keywords "sleep" or "sleep apnea" or "sleep
disordered breathing" and "pollution" and "children" in
"Title/Abstract/Keywords", with language restriction (non-English paper) and no
date limitation to present. The tobacco smoke pollution is well established
linking and is not considered for the present subject. We examined the strength
of the evidence according to the Oxford Centre for Evidence-Based Medicine [2011]
and the Centre for Evidence-Based Medicine [2009]. RESULTS: A total of 105
articles were identified, but 97 of these had to be excluded after an accurate
reading of the title, abstract or full text. In the end, eight studies were
selected for our analysis for a total of a total of 5,826 children. The results
suggest an involvement (grade C) of environmental (not from voluptuary habits)
pollution in the worsening of sleep-disordered breathing in children.
CONCLUSIONS: To date, some studies reported significant differences between areas
with higher and lower pollutants and the interventions on indoor pollution
reduced sleep-disordered breathing in children. Therefore, although the relevance
of the argument is high, the number of studies and the interest in the subject
seems at this time quite limited.
PMID- 28503419
TI - Comparison of the impact of epigallocatechin gallate and ellagic acid in an
experimental cataract model induced by sodium selenite.
AB - AIM: To compare the potential protective effects of epi-gallocatechin gallate
(EGCG) and ellagic acid (EA) in an experimental cataract model. METHODS: Twenty
eight Spraque-Dawley rat pups were assigned into four groups. All the rats,
except for those in the control group, were injected subcutaneously sodium
selenite to induce experimental cataract on the postpartum ninth day, and between
10th and 14th days. Rats in the sham, EGCG, and EA groups were intraperitoneally
administered 50 mg/(kg.d) saline solution, 50 mg/(kg.d) EGCG and 200 mg/(kg.d)
EA, respectively. The reduced glutathione (GSH) and malondialdehyde (MDA) levels,
total antioxidant status (TAS) and total oxidant status (TOS) in lens
supernatants were measured. RESULTS: The mean cataract gradings in EGCG and EA
groups were found to be significantly lower than that in sham group (P<0.001).
The mean GSH levels and TASs in EGCG and EA groups were significantly higher than
that in sham group while mean MDA levels and TOSs in EGCG and EA groups were
significantly lower than that in the sham group (P<0.001). CONCLUSION: EGCG and
EA have protective effects on cataract development via the inhibition of
oxidative stress.
PMID- 28503420
TI - Oxidative stress affects retinal pigment epithelial cell survival through
epidermal growth factor receptor/AKT signaling pathway.
AB - AIM: To investigate the cross-talk between oxidative stress and the epidermal
growth factor receptor (EGFR)/AKT signaling pathway in retinal pigment epithelial
(RPE) cells. METHODS: Human RPE cell lines (ARPE-19 cell) were treated with
different doses of epidermal growth factor (EGF) and hydrogen peroxide (H2O2).
Cell viability was determined by a methyl thiazolyl tetrazolium assay. Cell
proliferation was examined by a bromodeoxyuridine (BrdU) incorporation assay.
EGFR/AKT signaling was detected by Western blot. EGFR localization was also
detected by immunofluorescence. In addition, EGFR/AKT signaling was intervened
upon by EGFR inhibitor (erlotinib), PI3K inhibitor (A66) and AKT inhibitor (MK
2206), respectively. H2O2-induced oxidative stress was blocked by antioxidant N
acetylcysteine (NAC). RESULTS: EGF treatment increased ARPE-19 cell viability and
proliferation through inducing phosphorylation of EGFR and AKT. H2O2 inhibited
ARPE-19 cell viability and proliferation and also suppressed EGF-stimulated
increase of RPE cell viability and proliferation by affecting the EGFR/AKT
signaling pathway. EGFR inhibitor erlotinib blocked EGF-induced phosphorylation
of EGFR and AKT, while A66 and MK-2206 only blocked EGF-induced phosphorylation
of AKT. EGF-induced phosphorylation and endocytosis of EGFR were also affected by
H2O2 treatment. In addition, antioxidant NAC attenuated H2O2-induced inhibition
of ARPE-19 cell viability through alleviating reduction of EGFR, and
phosphorylated and total AKT proteins. CONCLUSION: Oxidative stress affects RPE
cell viability and proliferation through interfering with the EGFR/AKT signaling
pathway. The EGFR/AKT signaling pathway may be an important target in oxidative
stress-induced RPE cell dysfunction.
PMID- 28503422
TI - Inhibition of cell proliferation, migration and apoptosis in blue-light
illuminated human retinal pigment epithelium cells by down-regulation of HtrA1.
AB - AIM: To investigate the effect of HtrA1 on the proliferation, migration and
apoptosis of human retinal pigment epithelium (RPE) cells in the light injured
model, as well as the expression of the apoptosis related molecules. METHODS: The
human RPE cell line ARPE-19 was exposed to blue light to establish the light
injured model. The cells were transfected with HtrA1 siRNA to knockdown HtrA1
expression. Subsequent expression of HtrA1 was determined by real-time polymerase
chain reaction (RT-PCR) and Western blot, respectively. Changes in cell
proliferation, migration and apoptosis were assessed by cell counting kit-8 (CCK
8), Transwell assay and flow cytometry respectively, as well as changes in the
mRNA and protein levels of Bax, Caspase-3 and Bcl-2 expression. RESULTS: HtrA1
was highly expressed in ARPE-19 cells after blue light irradiation. Knockdown of
HtrA1 expression inhibited the proliferation, migration and apoptosis of the blue
light-irradiated ARPE-19 cells (P<0.05). Bax and Caspase-3 expression were
significantly reduced both at mRNA and protein levels (P<0.05) after siRNA
treatment. Bcl-2 expression significantly increased in blue-light-irradiated ARPE
19 cells after siRNA interference (P<0.05). CONCLUSION: Silence of HtrA1 may
inhibit the proliferation, migration and apoptosis of ARPE-19 cells in light
injured model. Moreover, HtrA1 suppression in blue-light-irradiated ARPE-19 cells
may ameliorate cell apoptosis through down-regulation of Bax and Caspase-3, and
up-regulation of Bcl-2 expression.
PMID- 28503421
TI - Differential expression of breast cancer-resistance protein, lung resistance
protein, and multidrug resistance protein 1 in retinas of streptozotocin-induced
diabetic mice.
AB - AIM: To investigate the altering expression profiles of efflux transporters such
as breast cancer-resistance protein (BCRP), lung resistance protein (LRP), and
multidrug resistance protein 1 (MDR1) at the inner blood-retinal barrier (BRB)
during the development of early diabetic retinopathy (DR) and/or aging in mice.
METHODS: Relative mRNA and protein expression profiles of these three efflux
transporters in the retina during the development of early DR and/or aging in
mice were examined. The differing expression profiles of Zonula occludens 1 (ZO
1) and vascular endothelial growth factor-A (VEGFA) in the retina as well as the
perfusion characterization of fluorescein isothiocyanate (FITC)-dextran and Evans
blue were examined to evaluate the integrity of the inner BRB. RESULTS: There
were significant alterations in these three efflux transporters' expression
profiles in the mRNA and protein levels of the retina during the development of
diabetes mellitus and/or aging. The development of early DR was confirmed by the
expression profiles of ZO-1 and VEGFA in the retina as well as the compromised
integrity of the inner BRB. CONCLUSION: The expression profiles of some efflux
transporters such as BCRP, LRP, and MDR1 in mice retina during diabetic and/or
aging conditions are tested, and the attenuated expression of BCRP, LRP, and MDR1
along with the breakdown of the inner BRB is found, which may be linked to the
pathogenesis of early DR.
PMID- 28503423
TI - MicroRNA-126: a promising novel biomarker in peripheral blood for diabetic
retinopathy.
AB - AIM: To investigate the content of serum microRNA-126 (miR-126) and its role in
screening retinal endothelial injury and early diagnosis of proliferative
diabetic retinopathy. METHODS: The study included 184 serum samples, 59 samples
from healthy individuals, 44 samples from diabetes mellitus (DM) patients without
diabetic retinopathy (NDR), 42 from non-proliferative diabetic retinopathy (NPDR)
patients and 39 samples from proliferative diabetic retinopathy (PDR) patients.
The expression of miR-126 was evaluated using a real-time quantitative polymerase
chain reaction. RESULTS: The serum content of miR-126 declined as the damage
degree in the retina. There was significant difference between the two
retinopathy groups (P<0.001). No difference was observed in miR-126 content
between healthy individuals and NDR patients (P>0.05). Receiver operating
characteristic curve (ROC) analyses indicated that serum miR-126 had significant
diagnostic value for PDR. It yielded an area under the curve (AUC) of ROC of
0.976 with 81.21% sensitivity and 90.34% specificity in discriminating PDR from
healthy controls, and an AUC of ROC of 0.919 with 84.75% sensitivity and 94.41%
specificity in discriminating NDR and NPDR from healthy controls. When the
diagnostic threshold was greater than or equal to 8.43, there was an increase in
the possibility of NPDR. When the content of miR-126 was less than or equal to
5.02, the possibility of the occurrence of PDR increased. CONCLUSION: Serum miR
126 can serve as a non-invasive biomarker for screening retinal endothelial
injury and early diagnosis PDR.
PMID- 28503424
TI - Interleukin-13 and age-related macular degeneration.
AB - AIM: o identify the effects of interleukin (IL)-13 on retinal pigment epithelial
(RPE) cells and the IL-13 level in aqueous humor of age-related macular
degeneration (AMD) patients. METHODS: IL-13 levels in aqueous humor specimens
from AMD patients were detected with enzyme-linked immunosorbent assay (ELISA).
ARPE-19 cells were treated with 10 ng/mL IL-13 for 12, 24, and 48h. The cell
proliferaton was evaluated by the MTS method. The mRNA and protein levels of
alpha-SMA and ZO-1 were evaluated with quantitative real-time polymerase chain
reaction (qRT-PCR) and Western blot respectively. The expression of tumor
necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta) and
vascular endothelial growth factor (VEGF) were assessed by ELISA. RESULTS: IL-13
levels in the aqueous humor of patients with AMD were significantly higher than
those in the control (167.33+/-17.64 vs 27.12+/-5.65 pg/mL; P<0.01). In vitro, IL
13 of high concentrations (10, 15, and 20 ng/mL) inhibited ARPE-19 cell
proliferation. alpha-SMA mRNA in ARPE-19 cell were increased (1.017+/-0.112 vs
1.476+/-0.168; P<0.001) and ZO-1 decreased (1.051+/-0.136 vs 0.702+/-0.069;
P<0.001) after treated with 10 ng/mL IL-13 for 48h. The protein expression of
alpha-SMA and ZO-1 also showed the same tendency (alpha-SMA: P=0.038; ZO-1:
P=0.008). IL-13 significantly reduced the level of TNF-alpha (44.70+/-1.67 vs
31.79+/-3.53 pg/mL; P=0.005) at 48h, but the level of TGF-beta2 was significantly
increased from 34.44+/-2.92 to 57.61+/-6.31 pg/mL at 24h (P=0.004) and from
61.26+/-1.11 to 86.91+/-3.59 pg/mL at 48h (P<0.001). While expressions of VEGF
didn't change after IL-13 treatment. CONCLUSION: IL-13 in vitro inhibit ARPE-19
cell proliferation and expression in the aqueous may be associated with AMD.
PMID- 28503425
TI - Neuroprotective effects of gypenosides in experimental autoimmune optic neuritis.
AB - AIM: To determine whether gypenosides have protective effects in experimental
autoimmune optic neuritis (EAON). METHODS: Mice were randomly divided into seven
groups: control group, model group, three different density gypenosides
monotherapy, methylprednisolone monotherapy, combination of gypenosides and
methylprednisolone group. The control group was subcutaneously injected with oil
emulsion adjuvant and all other groups were subcutaneously immunized with an
emulsified mixture of myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide to
induce EAON. Mice in the gypenosides groups were administered injections daily
with three concentrations (15 mg/kg, 30 mg/kg, 45 mg/kg) of gypenosides
respectively. Mice in the methylprednisolone group and the combination treatment
group were injected daily with methylprednisolone (20 mg/kg) or
methylprednisolone (20 mg/kg) + gypenosides (30 mg/kg), respectively. After MOG
immunization, visual evoked potential (VEP), optical coherence tomography (OCT),
and histopathologic examination were performed at 14, 20, 30, and 40d post
inoculation (p.i.). All results were expressed as mean+/-SEM. The data were
evaluated by one-way ANOVA followed by Tukey or Games-Howell test. RESULTS:
Compared with the control group, p2 latency was prolonged in the model group
(P=0.041). Combination treatment can alleviated the change in VEP at 20d p.i.
(P=0.012). Average peripapillary retinal nerve fiber layer (RNFL) thickness was
reduced in the model group (P=0.000, 30d; P=0.000, 40d) and gypenosides treatment
remarkably diminished the degree of RNFL degeneration at 30d and 40d p.i
(P=0.000, 30d; P=0.000, 40d). The pathomorphological results showed a decrease in
demye-lination (P=0.020) and inflammatory reactions in the combination group
compared with the model group (20d p.i.). Gypenosides treatment also alleviated
the degree of axonal loss (40d p.i.) (P=0.003). CONCLUSION: Treatment with
gypenosides exerts protective effects on retinal nerve fibers and axons in EAON.
When combined with gypenosides, methylprednisolone reduces demyelination in the
acute stage of EAON.
PMID- 28503426
TI - Expression and role of specificity protein 1 in the sclera remodeling of
experimental myopia in guinea pigs.
AB - AIM: To study the expression of collagen I and transcription factor specificity
protein 1 (Sp1), a transforming growth factor-beta1 (TGF-beta1) downstream
target, and reveal the impact of the TGF-beta1-Sp1 signaling pathway on collagen
remodeling in myopic sclera. METHODS: Seventy-five 1-week-old guinea pigs were
randomly divided into normal control, form deprivation myopia (FDM), and self
control groups. FDM was induced for different times using coverage with
translucent latex balloons and FDM recovery was performed for 1wk after 4wk
treatment; then, changes in refractive power and axial length were measured.
Immunohistochemistry and reverse transcription-polymerase chain reaction were
used to evaluate dynamic changes in collagen I and Sp1 expression in the sclera
of guinea pigs with emmetropia and experimental myopia, and the relationship
between collagen I and Sp1 levels was analyzed. RESULTS: In the FDM group, the
refractive power was gradually changed (from 2.09+/-0.30 D at week 0 to -1.23+/
0.69 D, -4.17+/-0.59 D, -7.07+/-0.56 D, and -4.30+/-0.58 D at weeks 2, 4, 6, and
1wk after 4wk, respectively; P<0.05), indicating deepening of myopia. The axial
length was increased (from 5.92+/-0.39 mm at week 0 to 6.62+/-0.36 mm, 7.30+/
0.34 mm, 7.99+/-0.32 mm, and 7.41+/-0.36 mm at weeks 2, 4, 6, and 1wk after 4wk;
P<0.05). The mRNA and protein expression of Sp1 and collagen I in the sclera of
the FDM group was lower than that of the control groups (P<0.05), and the
reduction was eye-coverage time-dependent. Furthermore, correlation between Sp1
and collagen I down-regulation in the myopic sclera was observed. CONCLUSION: Our
data indicate that transcription factor Sp1 may be involved in the regulation of
type I collagen synthesis/degradation during myopic sclera remodeling, suggesting
that TGF-beta1 signaling plays a role in the development and progression of
myopia.
PMID- 28503427
TI - Expressions of matrix metalloproteinases 1 and 3 and their tissue inhibitors in
the conjunctival tissue and fibroblasts cultured from conjunctivochalasis.
AB - AIM: To investigate the expression of matrix metalloproteinases 1 and 3 (MMP-1
and MMP-3) and their tissue inhibitors of metalloproteinases 1 and 3 (TIMP-1 and
TIMP-3) in the conjunctiva of eyes with conjunctivochalasis (CCh). METHODS: The
conjunctival tissue was obtained from the CCh patients and controls, the
MMPs/TIMPs expression concentration was determined by enzyme-linked immuno
sorbent assay (ELISA) and immunofluorescence staining. The expression levels of
MMPs/TIMPs in the CCh fibro-blasts were determined by analyzing its concentration
in the cellular supernatant that was abstracted from the in vitro cultured CCh
fibroblasts. RESULTS: MMP-1 and MMP-3 levels determined by ELISA were both
significantly higher in the CCh group than that in the control group (P=0.042,
0.022, respectively), so was the levels of TIMP-1 (P=0.010). No significant
difference in the expression of TIMP-3 in conjunctiva was found between the two
groups (P=0.298). The expression of MMP-1 and MMP-3 were both up-regulated
significantly in the CCh group (P=0.040, 0.001, respectively) on immuno
fluorescence staining. MMP-1 and MMP-3 expression in the fibroblasts were both
significantly higher in the CCh group than that in the control group (P=0.027,
0.001, respectively), while neither the TIMP-1 nor TIMP-3 expression was
significantly different between the two groups (P=0.421, 0.237, respectively).
CONCLUSION: The overexpression of MMP-1 and MMP-3 in conjunctival tissue and
fibroblasts may play an important role in the pathogenesis and development of
CCh.
PMID- 28503428
TI - Soluble expression of recomb inant cMyc, Klf4, Oct4, and Sox2 proteins in
bacteria and transduction into living cells.
AB - AIM: To develop a new method to produce recombinant reprogramming proteins, cMyc,
Klf4, Oct4, and Sox2, in soluble format with low cost for the generation of
induced pluripotent stem cells (iPSCs). METHODS: A short polypeptide sequence
derived from the HIV trans-activator of transcription protein (TAT) and the
nucleus localization signal (NLS) polypeptide were fused to the N terminus of the
reprogramming proteins and they were constructed into pCold-SUMO vector which can
extremely improve the solubility of recombinant proteins. Then these vector
plasmids were transformed into E. coli BL21 (DE3) Chaperone competent cells for
amplification. The solubility of these recombinant proteins was determined by SDS
PAGE and Coomassie brilliant blue staining. The recombinant proteins were
purified by Ni-NTA resin and identified by Western blot. The transduction of
these proteins into HEK 293T cells were evaluated by immunofluorescence staining.
RESULTS: These four reprogramming proteins could be produced in soluble format in
pCold-SUMO expression vector system with the assistance of chaperone proteins in
bacteria. The proteins were purified successfully with a purity of over 70% with
a relative high transduction rate into 293 cells. CONCLUSION: The results in the
present study indicate the four important reprogramming proteins, cMyc, Klf4,
Oct4, and Sox2, can be produced in soluble format in bacteria with low cost. Our
new method thus might be expected to greatly contribute to the future study of
iPSCs.
PMID- 28503429
TI - Suitability of open-field autorefractors as pupillometers and instrument design
effects.
AB - AIM: To determine the agreement and repeatability of the pupil measurement
obtained with VIP-200 (Neuroptics), PowerRef II (Plusoptix), WAM-5500 (Grand
Seiko) and study the effects of instrument design on pupillometry. METHODS: Forty
patients were measured twice in low, mid and high mesopic. Repeatability was
analyzed with the within-subject standard deviation (Sw) and paired t-tests.
Agreement was studied with Bland-Altman plots and repeated measures ANOVA.
Instrument design analysis consisted on measuring pupil size with PowerRef II
simulating monocular and binocular conditions as well as with proximity cues and
without proximity cues. RESULTS: The mean difference (+/-standard deviation)
between test-retest for low, mid and high mesopic conditions were, respectively:
0.09 (+/-0.16), -0.05 (+/-0.18) and -0.08 (+/-0.23) mm for Neuroptics, -0.05 (+/
0.17), -0.12 (+/-0.23) and -0.17 (+/-0.34) mm for WAM-5500, -0.04 (+/-0.27),
0.13 (+/-0.37) and -0.11 (+/-0.28) mm for PowerRef II. Regarding agreement with
Neuroptics, the mean difference for low, mid and high mesopic conditions were,
respectively: -0.48 (+/-0.35), -0.83 (+/-0.52) and -0.38 (+/-0.56) mm for WAM
5500, -0.28 (+/-0.56), -0.70 (+/-0.55) and -0.61 (+/-0.54) mm for PowerRef II.
The mean difference of binocular minus monocular pupil measurements was: -0.83
(+/-0.87) mm; and with proximity cues minus without proximity cues was: -0.30 (+/
0.77) mm. CONCLUSION: All the instruments show similar repeat-ability. In all
illumination conditions, agreement of Neuroptics with WAM-5500 and PowerRef II is
not good enough, which can be partially induced due to their open field design.
PMID- 28503430
TI - Long-term rotational stability and visual outcomes of a single-piece hydrophilic
acrylic toric IOL: a 1.5-year follow-up.
AB - AIM: To evaluate the rotational stability and visual outcomes of a single-piece
hydrophilic acrylic toric intraocular lenses (IOL) over a 1.5-year follow-up
period. Data from the 6-month follow-up study have been previously reported.
METHODS: Forty eyes of 26 cataract patients (mean age: 72.8+/-7.9y) with pre
existing corneal astigmatism of 1.0 to 2.6 D were enrolled in the study. Mean
axial length was 23.17+/-0.88 mm. Main outcome measures after implantation of the
Torica-aA IOL (HumanOptics) were IOL rotational stability, subjective refraction,
astigmatism correction, uncorrected and corrected distance visual acuity (UDVA,
CDVA). RESULTS: There was no significant change in the parameters evaluated
between the 6-month and 1.5-year follow-ups. At last visit, mean absolute IOL
rotation (objective method) was 1.81 degrees +/-1.87 degrees (range 0.00 degrees
to 7.20 degrees ) with 78.6% of eyes having IOL rotation <3 degrees , 92.9% of
eyes <5 degrees and 100% of eyes <8 degrees . No patient required secondary IOL
repositioning during the course of the study. Mean residual refractive cylinder
was -0.60+/-0.40 D. There was a significant reduction in the magnitude of the J0
vector postoperatively (P<0.0001) with a mean absolute change of 0.76+/-0.40 D.
The mean J45 vector was close to zero preoperatively and postoperatively and
didn't change significantly (P=0.28). Mean monocular UDVA and CDVA was 0.09+/
0.12 logMAR and -0.01+/-0.12 logMAR, respectively. No treatment with Nd:YAG laser
was required. CONCLUSION: The Torica-aA IOL shows good and stable visual
performance and rotational stability over a 1.5-year follow-up period.
PMID- 28503431
TI - A pilot study of intraocular lens explantation in 69 eyes in Chinese patients.
AB - AIM: To study the effects of intraocular lens (IOL) explantation and demographic
characteristics. METHODS: Retrospective non-comparative case series. Clinical
data recorded from patient charts included the following: demographic,
preoperative and postoperative characteristics; complications; surgical methods,
and changes in visual acuity. RESULTS: A total of 69 eyes in 67 Chinese patients
who received IOL explants were studied. The patients' mean age at the time of
explantation was 46.1 years old [SD 22.5 (6-85)], and 37 patients were female
(55.2%). Regarding employment, 47.8% were farmers, 23.9% were retired, 16.4% were
students, 4.5% were unemployed, 3% were workers, and 4.5% were other (including
staff members, teachers and officers). The main reasons for explantation were
dislocation/decentration in 41 cases (59.4%) and retinal detachment in 10 cases
(14.5%). The third most prevalent cause was incorrect lens power in 7 eyes
(10.1%). The remaining reasons were endophthalmitis in 6 cases (8.7%), posterior
capsular opacity in 3 eyes (4.3%), and impacting retinal surgery operation in 2
cases (2.9%). The main comorbidities were high myopia in 18 eyes (26.1%), trauma
in 8 eyes (11.6%), retinal detachment in 6 eyes (8.7%), congenital cataracts in 8
eyes (11.6%), and Marfan's syndrome in 2 eyes (2.9%). The mean time from
implantation to explantation was 4.0y [SD 4.2 (0.005-15)]. Treatment after
explantation included posterior chamber IOL implantation in 44 eyes (63.8%) and
aphakia in 25 eyes (36.2%). After surgery, the best corrected visual ability
(BCVA) was improved in 50 cases (72.5%), including 28 patients (40.6%) in whom
visual ability was improved by more than two lines. CONCLUSION:
Dislocation/decentration is the main cause for explantation, and high myopia is a
main risk factor. Posterior chamber IOL implantation remains the most elected
treatment after explantation.
PMID- 28503432
TI - Nutrient patterns and risk of cataract: a case-control study.
AB - AIM: To assess the relation between nutrient patterns and cataract risk. METHODS:
This is a hospital-based case-control study with 97 cataract patients and 198
matched controls. Dietary consumption was collected through a valid food
frequency questionnaire (FFQ). Nutrient patterns were detected by applying factor
analysis. Unconditional logistic regression models were used to estimate odds
ratio (ORs) and 95%CIs. RESULTS: We extracted 5 main nutrient patterns. Factor 1
included niacin, thiamin, carbohydrates, protein, zinc, vitamin B6 and sodium
(sodium pattern). Factor 2 was characterized by oleic acid, monounsaturated fats,
polyunsaturated fats, linoleic acid, trans fatty acid, linolenic acid, vitamin E
and saturated fats (fatty acid pattern). The third factor represented high intake
of vitamin B12, vitamin D, cholesterol and calcium (mixed pattern). The 4th
pattern was high in intake of beta and alpha carotene, vitamin A and vitamin C
(antioxidant pattern). Finally, the 5th pattern loaded heavily on docosahexaenoic
acid (DHA) and eicosapentaenoic acid (EPA) (omega-3 pattern). In crude and
multivariate analysis, the sodium pattern was associated with increased risk of
cataract (OR=1.97, 95%CI: 1.09-3.96). The fatty acid pattern elevated the risk of
cataract (OR=1.94, 95%CI: 1.1-3.86). Antioxidant pattern was associated with a
significant 79% reduced risk (2nd category compared with the 1st). Omega-3
pattern was significantly negatively associated with risk of cataract (P=0.04).
CONCLUSION: These findings imply that nutrient patterns reflecting a combined
consumption of nutrients might be important in the etiology of cataract.
Additional studies with more efficient designs are warranted to confirm our
findings.
PMID- 28503433
TI - Selective laser trabeculoplasty in pseudophakic and phakic eyes: a prospective
study.
AB - AIM: To compare the efficacy of selective laser trabeculoplasty (SLT) in
replacing medical therapy in pseudophakic and phakic eyes. METHODS: Subgroup of a
prospective randomized clinical trial including patients with primary open angle
glaucoma or ocular hypertension controlled with medication. Of 38 pseudophakic
eyes were matched with 38 phakic eyes. SLT was offered as a way to decrease
medication while maintaining the same low eye pressure. SLT was performed over
360 degrees , at 3ns, spotsize 400 um, 100 spots. Data [intraocular pressure
(IOP), number of medications needed] were measured at 1h, 1wk, 1, 3, 6 and 12mo.
An independent-samples t-test was performed to compare baseline characteristics
of the phakic and the pseudophakic group and differences in evolution of mean IOP
and number of used medications. Chi-squared analysis was performed to investigate
proportions of fast, slow and non-responders. RESULTS: The mean IOP measurement
was 13.00+/- 2.88 mm Hg in the phakic group (38 eyes) and 13.51+/-3.06 mm Hg in
the pseudophakic group (38 eyes) (P>0.05). This changed little after SLT and IOP
lowering effect was comparable between the two groups. Main aim however was to
lower the amount of medication needed. In the phakic group medication lowered
from 1.29+/-0.62 at baseline, to 0.15+/-0.46 after 12mo; a reduction of 88.37%.
In the pseudophakic group, used medication changed from 1.71+/-1.04, to 0.41+/
0.61; a 76.02% reduction. The differences were not statistically significant at
any time point (P>0.05). IOP lowering occurred slightly faster in the
pseudophakic group (50% of patients after one week) than in the phakic group (68%
of patients after more than 4wk). The difference was not significant (P>0.05).
CONCLUSION: IOP lowering effect of SLT is comparable between phakic and
pseudophakic eyes.
PMID- 28503434
TI - Comparison of isolated-check visual evoked potential and standard automated
perimetry in early glaucoma and high-risk ocular hypertension.
AB - AIM: To compare the diagnostic performance of isolated-check visual evoked
potential (icVEP) and standard automated perimetry (SAP), for evaluating the
application values of icVEP in the detection of early glaucoma. METHODS: Totally
144 subjects (288 eyes) were enrolled in this study. icVEP testing was performed
with the Neucodia visual electrophysiological diagnostic system. A 15% positive
contrast (bright) condition pattern was used in this device to differentiate
between glaucoma patients and healthy control subjects. Signal-to-noise ratios
(SNR) were derived based on a multivariate statistic. The eyes were judged as
abnormal if the test yielded an SNR<=1. SAP testing was performed with the
Humphrey Field Analyzer II. The visual fields were deemed as abnormality if the
glaucoma hemifield test results outside normal limits; or the pattern standard
deviation with P<0.05; or the cluster of three or more non-edge points on the
pattern deviation plot in a single hemifield with P<0.05, one of which must have
a P<0.01. Disc photographs were graded as either glaucomatous optic neuropathy or
normal by two experts who were masked to all other patient information.
Moorfields regression analysis (MRA) used as a separate diagnostic classification
was performed by Heidelberg retina tomograph (HRT). RESULTS: When the disc
photograph grader was used as diagnostic standard, the sensitivity for SAP and
icVEP was 32.3% and 38.5% respectively and specificity was 82.3% and 77.8%
respectively. When the MRA Classifier was used as the diagnostic standard, the
sensitivity for SAP and icVEP was 48.6% and 51.4% respectively and specificity
was 84.1% and 78.0% respectively. When the combined structural assessment was
used as the diagnostic standard, the sensitivity for SAP and icVEP was 59.2% and
53.1% respectively and specificity was 84.2% and 84.6% respectivlely. There was
no statistical significance between the sensitivity or specificity of SAP and
icVEP, regardless of which diagnostic standard was based on. CONCLUSION: The
diagnostic performance of icVEP is not better than that of SAP in the detection
of early glaucoma.
PMID- 28503435
TI - Evaluation of hyperreflective foci as a prognostic factor of visual outcome in
retinal vein occlusion.
AB - AIM: To evaluate the potential role of hyperreflective foci (HF) as a prognostic
indicator of visual outcome in patients with macular edema (ME) due to retinal
vein occlusion (RVO). METHODS: We retrospectively reviewed 50 eyes of 50 patients
with ME due to ischemic central retinal vein occlusion (CRVO), non-ischemic CRVO
and branch retinal vein occlusion (BRVO) who were treated with anti-vascular
endothelial growth factor (anti-VEGF) at Beijing Tongren Eye Center from January
2013 to July 2016. All patients underwent best-corrected visual acuity (BCVA),
spectral domain optical coherence tomography (SD-OCT) at baseline and follow-up.
Such factors were evaluated and compared among three groups as baseline and final
BCVA, central retinal thickness (CRT), external limiting membrane (ELM) status
and the numbers of HF in different position. Multiple linear regression analysis
was employed to analyze the relationship between baseline HF and final BCVA.
Changes of HF before and after treatment were evaluated too. RESULTS: Among three
groups, HF could be located in each retinal layers, as well as in vitreous
cavity. The mean HF in outer retinal layer (ORL) at baseline was 5.29+/-8.48 in
ischemic CRVO with intact ELM, 1.93+/-2.76 in non-ischemic CRVO, and 1.75+/-2.05
in BRVO. With disrupted ELM, the mean HF in ORL increased. There was
statistically difference of HF in ORL between intact and disrupted ELM. The
numbers of HF in ORL were associated with poor visual outcome among three groups.
However, HF in inner retinal layer (IRL) and vitreous cavity were not associated
with poor visual outcome. Meanwhile, the baseline HF in ORL and vitreous cavity
reduced significantly in non-ischemic CRVO and BRVO after anti-VEGF treatment.
CONCLUSION: The numbers of HF in ORL are prognostic factors associated with the
final BCVA in patients with ME due to RVO after anti-VEGF treatment.
PMID- 28503437
TI - Comparison of postoperative optical quality according to the degree of
decentering of V4c implantable collamer lens.
AB - AIM: To evaluate the clinical outcomes of V4c implantable collamer lens (Hole
ICL) implantation with regard to the optical quality assessed according to
different degrees of decentering. METHODS: This included 49 eyes that received
conventional ICL and 94 eyes that received Hole ICL. The eyes that received Hole
ICL were divided into three groups according to the degree of decentering: group
1, central hole within 1 hole diameter (HD) from the pupil center; group 2,
central hole within 1 HD to 2 HD; and group 3, central hole within 2 HD to 3 HD.
Visual acuity (VA), intraocular pressure (IOP), and spherical equivalent (SE)
values were assessed at 1wk, 1 and 3mo after surgery. The ocular modulation
transfer function, Strehl ratio, objective scattering index, and higher order
aberrations (HOAs) were measured for 4-mm pupils at 3mo after surgery. RESULTS:
There were no significant differences in VA, IOP, and SE among the conventional
and Hole ICL groups. With regard to HOAs, values for coma and spherical
aberrations showed no differences. The total HOA and trefoil values were
significantly higher in group 2 than in group 1 (P=0.02, 0.03, respectively).
There were no significant differences among groups with regard to other optical
quality parameter at 3mo after surgery. CONCLUSION: Our results suggest that Hole
ICL implantation provides satisfactory visual quality that is equivalent to that
provided by conventional ICL, regardless of the presence of central hole and
degree of decentering.
PMID- 28503436
TI - Association of choroidal thickness with early stages of diabetic retinopathy in
type 2 diabetes.
AB - AIM: To assess the correlation between choroidal thickness (CT) and the early
stages of diabetic retinopathy (DR) in type 2 diabetic patients. METHODS: We
divided 83 diabetic patients (51-80 years of age; 50 females) into non diabetic
retinopathy group (NDR) and mild/moderate nonproliferative diabetic retinopathy
(NPDR) group, and compared them with 26 non-diabetic control subjects (51-78
years of age; 16 females). Subfoveal choroidal thickness (SFCT) and parafoveal
choroidal thickness (PFCT) were measured using enhanced depth imaging spectral
domain optical coherence tomography (EDI-OCT). Ocular health status, disease
duration, body mass index, and hemoglobin A1c (HbA1c) were recorded. RESULTS: The
mean ages of the NDR, NPDR, and control groups were 68.0+/-6.9y, 67.8+/-6.4y, and
65.1+/-6.3y, respectively (P=0.17). Pearson correlation of the right and left
eyes for the control subjects was 0.95 and for the NDR subjects was 0.93. SFCT
for the right eyes of the controls was 252.77+/- 41.10 um, which was
significantly thicker than that of the right eyes in NDR group (221.51+/-46.56
um) and the worse eyes of the NPDR group (207.18+/-61.87 um; ANOVA, P<0.01). In
the diabetic patients pooled together, age was the only variable significantly
associated with SFCT (multiple linear regression analysis, P=0.01). CONCLUSION:
CT decreased significantly in the NDR and mild/moderate NPDR eyes compared with
the control eyes. Age is significantly associated with SFCT in the diabetic
patients. Diabetic choroidopathy may be present before clinical retinopathy.
PMID- 28503438
TI - Comparison of visual effects of FS-LASIK for myopia centered on the coaxially
sighted corneal light reflex or the line of sight.
AB - AIM: To compare visual quality after femtosecond laser in situ keratomileusis (FS
LASIK), between the coaxially sighted corneal light reflex (CSCLR) group and
conventional ablation line of sight (LOS) group. METHODS: In total, 243 eyes (122
patients) were treated with centration on the CSCLR (visual axis) and 238 eyes
(119 patients) treated with centration on the pupil center (LOS). Postoperative
outcomes [uncorrected visual acuity (UCVA), best spectacle-corrected visual
acuity (BSCVA)], safety index, efficacy index, refractive outcome, ablation
center distance from the visual axis, corneal high-order aberrations, subjective
discomfort glare and shadowing incidence rate, and contrast sensitivity at 1, 3,
and 6mo were measured and compared. RESULTS: The mean age was 27.77+/-7.1y in the
CSCLR group and 26.03+/-7.70y in the LOS group. Preoperatively, the manifest
refraction spherical equivalent (MRSE) was -6.68+/-2.60 D in the CSCLR group and
6.65+/-2.68 D in the LOS group. The postoperative UCVA, BSCVA, MRSE (-0.03+/
0.263 D in the CSCLR group, -0.05+/-0.265 D in the LOS group), efficacy index
(1.04, 1.03), and safety index (1.09, 1.08) were not significantly different
between the groups (all P>0.05). In total, 3% lost one line and more of BSCVA in
the CSCLR group, as 9% in the LOS group postoperatively (P<0.05). The ablation
center deviation was 0.20+/-0.15 mm from the visual axis (Pentacam system default
setting; range, 0-0.75 mm) in the CSCLR group, and 0.43+/-0.22 mm (range, 0-1.32
mm) in the LOS group (P<0.0001). Statistically significant greater augmentation
of total corneal higher-order aberrations (0.15+/-0.10 um and 0.20+/-0.12 um
respectively, P=0.03) and vertical and horizontal coma (P<0.0001) were noted in
the LOS group. Subjective discomfort glare and shadowing incidence rates were
8.59% and 17.5% in the CSCLR and LOS groups, respectively (P<0.05). The 1-month
postoperative contrast sensitivity visual acuity in the CSCLR group was
significantly higher than that in the LOS group on contrast (100%, 25%, 10%) with
a dark background, but there was no significant difference between the groups at
3 or 6m. CONCLUSION: Myopic LASIK centered on the CSCLR achieves significantly
lower induction of loss of BSCVA, corneal high-order aberrations, and lower risk
of subjective discomfort glare and shadowing, and lower decline in early contrast
sensitivity by comparison with centration on the LOS, giving advantages in visual
quality postoperatively.
PMID- 28503439
TI - Dry eye and corneal sensitivity after small incision lenticule extraction and
femtosecond laser-assisted in situ keratomileusis: a Meta-analysis.
AB - AIM: To assess the corneal sensitivity and the incidences of dry eye after small
incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ
keratomileusis (FS-LASIK). METHODS: The Meta-analysis was performed using RevMan
5.3. We searched on PubMed from inception to March 2016. Summary weighted mean
difference (WMD) and 95% confidence intervals (CIs) were used to analyze the
datum. Random-effects or fixed-effects models were chosen up to between-study
heterogeneity. The main outcomes were composed of the Ocular Surface Disease
Index (OSDI) scores, tear film break-up time (TBUT), Schirmer Test and corneal
sensitivity. RESULTS: Eight eligible studies including 772 eyes (386 in SMILE
group and 386 in FS-LASIK group) were identified. The parameters have no
significiant difference heterogeneity between SMILE and FS-LASIK group
preoperatively. There were significant differences between the two groups in OSDI
scores at one and three months postoperatively, in TBUT at one and three months
postoperatively, in corneal sensitivity at one week, about one month and three
months postoperatively. However, there was no significant difference observed in
Schirmer Test at the follow-up periods. CONCLUSION: Compare to FS-LASIK, dry eye
and the corneal sensitivity recover better in the SMILE group, in first three
months after the surgery.
PMID- 28503440
TI - MnSOD Val16Ala polymorphism associated with retinopathy risk in diabetes: a
PRISMA-compliant Meta-analysis of case-control studies.
AB - AIM: To investigate the association of Manganese superoxide dismutase (MnSOD)
Val16Ala polymorphism with diabetic retinopathy (DR). METHODS: PubMed, Embase,
China National Knowledge Infrastructure, and Wanfang databases were searched. The
pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to
evaluate the strength of the association. Subgroup, sensitivity, and cumulative
analyses were performed. Publication bias was also analyzed. RESULTS: Eight
studies were included in the pooled analysis. The MnSOD Val16Ala polymorphism was
associated with the risk of DR under the dominant model (OR=0.66, 95%CI=0.48
0.91, P<0.0001), this result was demonstrated to be relatively stable in
cumulative analysis. No significant publication bias was found. This polymorphism
was also associated with the risk of DR in Caucasians under the dominant model
(OR=0.64, 95%CI=0.42-0.97, P=0.04,) and in Asians under the recessive model
(OR=0.31, 95%CI=0.11-0.88, P=0.03). CONCLUSION: These findings suggest that the
MnSOD Val16Ala polymorphism is a risk factor for DR, and that more attention
should be paid to carriers of these susceptibility genes.
PMID- 28503441
TI - Applications of CRISPR/Cas9 in retinal degenerative diseases.
AB - Gene therapy is a potentially effective treatment for retinal degenerative
diseases. Clustered regularly interspaced short palindromic repeats
(CRISPR)/CRISPR-associated protein 9 (Cas9) system has been developed as a new
genome-editing tool in ophthalmic studies. Recent advances in researches showed
that CRISPR/Cas9 has been applied in generating animal models as well as gene
therapy in vivo of retinitis pigmentosa (RP) and leber congenital amaurosis
(LCA). It has also been shown as a potential attempt for clinic by combining with
other technologies such as adeno-associated virus (AAV) and induced pluripotent
stem cells (iPSCs). In this review, we highlight the main points of further
prospect of using CRISPR/Cas9 in targeting retinal degeneration. We also
emphasize the potential applications of this technique in treating retinal
degenerative diseases.
PMID- 28503443
TI - Vascular anomaly in the levator aponeurosis of neurofibromatosis type 1.
PMID- 28503442
TI - Clinical outcomes at one year following keratoconus treatment with accelerated
transepithelial cross-linking.
AB - This study evaluated the clinical outcomes in keratoconus corneas following
accelerated transepithelial corneal collagen cross-linking (CXL) (Avedro KXL(r)
system, Waltham, MA, USA) over one year of follow-up. The mean depth of the
demarcation line measured by optical coherence tomography (OCT) was 205.19 um.
One month after surgery, a non-statistically significant change was noted in
sphere (P=0.18) and in spherical equivalent (P=0.17), whereas a significant
improvement was observed in corrected distance visual acuity (P=0.04). A
significant change was observed in topographic astigmatism (P=0.03) and posterior
corneal a sphericity (P=0.04). Accelerated transepithelial CXL may be a useful
technique for the management of progressive keratoconus.
PMID- 28503444
TI - Keratoconus associated with Williams-Beuren syndrome: a new case report.
PMID- 28503445
TI - Optical coherence tomography angiography in incomplete acute Vogt-Koyanagi-Harada
disease.
PMID- 28503446
TI - Comment on hydration with Cefuroxime-a method for sealing a small leaking corneal
perforation.
PMID- 28503447
TI - Strengthening Health Systems to Provide Rehabilitation Services.
PMID- 28503448
TI - Resting-State Metabolism of Hand Knob Area on 18F-FDG PET-CT According to Hand
Function and Tractography of Corticospinal Tract After Stroke.
AB - OBJECTIVE: To correlate the resting metabolism of hand knob and hand function
after stroke, diffuse tensor tractography (DTT) and 18F-fluorodeoxyglucose
position emission tomography (18F-FDG PET) were used to evaluate constructible
state of white matter tract and metabolic state of gray matter, respectively.
METHODS: A total of 17 patients were included in the study, who had suffered a
stroke with hand weakness, after a stroke. They underwent diffusion tensor
analysis and FDG PET in the subacute period. The ratio of both hemisphere
parameters in voxel number of fibers, fractional anisotropy (FA) and apparent
diffusion coefficient obtained by corticospinal tract as constructed by DTT, and
the metabolism of hand knob area on cerebral cortex obtained from 18F-FDG PET
were calculated. Hand movement scale was evaluated on the day of FDG PET or
tractography, and at 6 months after onset. RESULTS: Difference of FA in DTT
between both hemispheres and hand knob metabolism in FDG PET significantly
correlated with the hand movement scale at the subacute stage and 6 months after
onset. However, the difference of both hemispheres in DTT and metabolism of hand
knob area was not significant. CONCLUSION: Resting metabolism on hand knob in FDG
PET correlated with hand function after stroke.
PMID- 28503449
TI - Feasibility of Rehabilitation Training With a Newly Developed, Portable, Gait
Assistive Robot for Balance Function in Hemiplegic Patients.
AB - OBJECTIVE: To investigate the clinical feasibility of a newly developed,
portable, gait assistive robot (WA-H, 'walking assist for hemiplegia') for
improving the balance function of patients with stroke-induced hemiplegia.
METHODS: Thirteen patients underwent 12 weeks of gait training on the treadmill
while wearing WA-H for 30 minutes per day, 4 days a week. Patients' balance
function was evaluated by the Berg Balance Scale (BBS), Fugl-Meyer Assessment
Scale (FMAS), Timed Up and Go Test (TUGT), and Short Physical Performance Battery
(SPPB) before and after 6 and 12 weeks of training. RESULTS: There were no
serious complications or clinical difficulties during gait training with WA-H. In
three categories of BBS, TUGT, and the balance scale of SPPB, there was a
statistically significant improvement at the 6th week and 12th week of gait
training with WA-H. In the subscale of balance function of FMAS, there was
statistically significant improvement only at the 12th week. CONCLUSION: Gait
training using WA-H demonstrated a beneficial effect on balance function in
patients with hemiplegia without a safety issue.
PMID- 28503450
TI - Balance Assessment in Subacute Stroke Patients Using the Balance Control Trainer
(BalPro).
AB - OBJECTIVE: To demonstrate the efficacy of the balance control trainer (BCT),
developed for training patients with balance problems, as a balance assessment
tool in subacute stroke patients. METHODS: A prospective cross-sectional study
was carried out on 38 subacute stroke patients in their first episode of a
stroke, and having the ability to maintain a standing position without aid for at
least 5 minutes. Patients were assessed using the BCT (BalPro) 43.7+/-35.7 days
after stroke. The balance was assessed using the Berg Balance Scale (BBS), the
Timed Up and Go Test (TUG), a 10-meter walking test (10mWT), a 6-minute walking
test (6MWT), and the Korean version of the Modified Barthel Index. The
correlation and validity between the BCT and various balance assessments were
analyzed. RESULTS: Statistically significant linear correlations were observed
between the BCT score and the BBS (r=0.698, p<0.001). A moderate to excellent
correlation was seen between the BCT score and 11 of the 14 BBS items. The BCT
scores and other secondary outcome parameters (6MWT r=0.392, p=0.048; TUG r=
0.471, p=0.006; 10mWT r=-0.437, p=0.012) had a moderate correlation. CONCLUSION:
Balance control training using the BCT (BalPro) showed significant statistical
correlation with the BBS, and could therefore be a useful additional balance
assessment tool in subacute stroke patients.
PMID- 28503451
TI - Association Between a Polymorphism in CASP3 and CASP9 Genes and Ischemic Stroke.
AB - OBJECTIVE: To investigate whether the polymorphisms of CASP3 gene (rs4647602,
intron A/C and rs1049216, UTR C/T) and CASP9 gene (rs1052576, Gln/Arg G/A and
rs1052571, Ser/Val T/C) were associated with the development, and clinical
severity of ischemic stroke and functional consequences after stroke. METHODS:
Genomic DNA from 121 ischemic stroke patients and 201 healthy control subjects
were extracted, and polymerase chain reaction products were sequenced. To
investigate the association of polymorphisms and the development, and National
Institutes of Health Stroke Scale (K-NIHSS), logistic regression models were
analyzed. RESULTS: Polymorphism of the untranslational region of CASP3
(rs1049216, UTR C/T) has been associated with the development of ischemic stroke
in codominant1 model (odds ratio [OR], 0.51; 95% confidence interval [CI], 0.29
0.88; p=0.017), in dominant model (OR, 0.57; 95% CI, 0.34-0.97; p=0.034), and in
the overdominant model (OR, 0.50; 95% CI, 0.29-0.87; p=0.011). A missense SNP of
CASP9 gene (rs1052571, Ser/Val T/C) was associated with the development of
ischemic stroke (OR, 1.93; 95% CI, 1.05-3.55; p=0.034 in recessive model).
CONCLUSION: These results indicate the possibility that CASP3 and CASP9 genes are
markers for the development of ischemic stroke.
PMID- 28503452
TI - Relation of Urinary Retention and Functional Recovery in Stroke Patients During
Rehabilitation Program.
AB - OBJECTIVE: To investigate the relationship between urinary retention and short
term functional recovery in subacute stage after stroke. METHODS: The medical
records of 94 patients admitted to the rehabilitation unit of Korea University
Guro Hospital were reviewed retrospectively. The postvoid residual urine (PVR)
was measured at least once a day using a bladder scan, and urinary retention (UR)
was defined when the daily PVR volume consistently checked more than 100 mL.
Clinical data and functional outcomes of patients in the rehabilitation ward were
collected. Functional outcomes were measured using the Mini-Mental State
Examination (MMSE), Berg Balance Scale (BBS), Functional Ambulation Category
(FAC) level, Fugl-Meyer Assessment (FMA), and Modified Barthel Index (MBI) at
admission (or transfer) and discharge. The data of patients with and without
urinary retention were compared and analyzed. RESULTS: Of the 94 participants, 25
patients were classified to the UR group and 69 were classified to the non-UR
group. At the initial stage of rehabilitation, the scores of MMSE, BBS, FAC, MBI
were significantly worse in the UR group (p<0.05). Both groups showed significant
improvements of all functional outcomes after rehabilitation (p<0.05). The non-UR
group showed more prominent recovery of BBS, FAC, MBI scores (p<0.05).
CONCLUSION: Urinary retention in post-stroke patients is significantly related to
the poor functional status at initial stage of rehabilitation, and also to poor
recovery after rehabilitation.
PMID- 28503453
TI - Relationship Between Motor Evoked Potential Response and the Severity of
Paralysis in Spinal Cord Injury Patients.
AB - OBJECTIVE: To investigate the relationship between motor evoked potential (MEP)
response and the severity of motor paralysis, evaluated according to the Korean
disability evaluation system in patients with spinal cord injury (SCI). METHODS:
We analyzed 192 lower limbs of 96 SCI patients. Lower limbs were classified
according to their motor scores, as determined by the International Standards for
Neurological Classification of Spinal Cord Injury: motor score <10 (group 1);
>=10 and <15 (group 2); >=15 and <20 (group 3); and >=20 (group 4). MEP responses
were classified as 'normal', 'delayed' or 'absent', based on their onset latency,
which was compared between the different motor score groups. RESULTS: MEP
responses and limb motor scores were highly correlated (p<0.001). There was a
significant difference of MEP responses between the motor score groups (p<0.001).
MEP response was markedly poorer in motor group 1 (limb motor score <10) than in
the other three groups (p<0.0001). However, there were no differences between the
three groups with motor scores of 10 or above. CONCLUSION: Clinical utility of
MEP as a complimentary tool to manual muscle tests could be limited to
discriminating motor score groups with severe paralysis, i.e., single lower limb
motor power grades of 0 or 1, and from grade 2, 3, and 4, or above, in the Korean
disability evaluation system.
PMID- 28503454
TI - Quantitative Assessment of Proprioception Using Dynamometer in Incomplete Spinal
Cord Injury Patients: A Preliminary Study.
AB - OBJECTIVE: To investigate the feasibility of a knee proprioception evaluation
using a dynamometer as a tool for evaluating proprioception of the lower
extremities in patients with incomplete spinal cord injury (SCI), and to explore
its usefulness in predicting the ambulatory outcome. METHODS: A total of 14 SCI
patients (10 tetraplegic, 4 paraplegic; all AIS D) were included in this study.
The passive repositioning error (PRE) and active repositioning error (ARE) were
measured with a dynamometer, along with tibial somatosensory evoked potential
(SSEP) and abductor hallucis motor-evoked potential (MEP). Ambulatory capacity
was assessed with the Walking Index for Spinal Cord Injury II (WISCI-II), both at
the time of the proprioception test (WISCI_i) and at least 6 months after the
test (WISCI_6mo). RESULTS: The PRE showed a negative correlation with WISCI_i (r=
0.440, p=0.034) and WISCI_6mo (r=-0.568, p=0.010). Linear multiple regression
showed the type of injury, lower extremities motor score, MEP, and PRE accounted
for 75.4% of the WISCI_6mo variance (p=0.080). CONCLUSION: Proprioception of the
knee can be measured quantitatively with a dynamometer in patients with
incomplete SCI, and PRE was related to the outcome of the ambulatory capacity.
Along with the neurological and electrophysiological examinations, a
proprioception test using a dynamometer may have supplementary value in
predicting the ambulatory capacity in patients with incomplete SCI.
PMID- 28503455
TI - Lesion Characteristics of Chronic Dysphagia in Patients With Supratentorial
Stroke.
AB - OBJECTIVE: To analyze the relationship between brain lesion location and type of
chronic dysphagia in patients with supratentorial stroke. METHODS: Data from 82
chronic stroke patients who underwent videofluoroscopic swallowing studies at >6
months after an initial stroke event were retrospectively analyzed. Delayed oral
transit time, delayed pharyngeal transit time, and the presence of aspiration
were extracted. A voxel-based lesion symptom mapping (VLSM) analysis was used to
correlate types of dysphagia with specific brain lesions. RESULTS: VLSM
identified several clusters of voxels that significantly correlated with type of
dysphagia. Delayed oral transit time mainly correlated with lesions in the left
inferior frontal lobe and precentral gyrus; delayed pharyngeal time mainly
correlated with lesions in the right basal ganglia and corona radiate; and
aspiration was mainly correlated with lesions in the putamen. CONCLUSION:
Understanding the association between lesion location and dysphagia in chronic
stroke patients is an important first step towards predicting permanent dysphagia
after stroke. Improved understanding of the neural correlates of dysphagia will
inform the utility of interventions for its treatment and prevention after
stroke.
PMID- 28503456
TI - Effect of Vallecular Ballooning in Stroke Patients With Dysphagia.
AB - OBJECTIVE: To investigate the improvement of dysphagia after balloon dilatation
and balloon swallowing at the vallecular space with a Foley catheter in stroke
patients. METHODS: This study was conducted between May 1, 2012 and December 31,
2015, and involved 30 stroke patients with complaints of difficulty in
swallowing. All patients underwent videofluoroscopic swallowing study (VFSS)
before and after vallecular ballooning. VFSS was performed with a 4 mL semisolid
bolus. For vallecular ballooning, two trainings were performed for at least 10
minutes, including backward stretching of the epiglottis and swallowing of a
balloon located in the vallecular space, by checking the movement of the Foley
catheter tip in real time using VFSS. RESULTS: After examination of the dysphagia
improvement pattern before and after vallecular ballooning, laryngeal elevation
(x-axis: pre 2.62+/-1.51 mm and post 3.54+/-1.93 mm, p=0.038; y-axis: pre 17.11+/
4.24 mm and post 22.11+/-3.46 mm, p=0.036), pharyngeal transit time (pre 5.76+/
6.61 s and post 4.08+/-5.49 s, p=0.043), rotation of the epiglottis (pre 53.24
degrees +/-26.77 degrees and post 32.45 degrees +/-24.60 degrees , p<0.001), and
post-swallow pharyngeal remnant (pre 41.31%+/-23.77% and post 32.45%+/-24.60%,
p=0.002) showed statistically significant differences. No significant difference
was observed in the penetration-aspiration scale score (pre 4.73+/-1.50 and post
4.46+/-1.78, p=0.391). CONCLUSION: For stroke patients with dysmotility of the
epiglottis and post-swallowing residue, vallecular ballooning can be considered
as an alternative method that can be applied without risk of aspiration in
dysphagia treatment.
PMID- 28503457
TI - The Association Between Fall History and Physical Performance Tests in the
Community-Dwelling Elderly: A Cross-Sectional Analysis.
AB - OBJECTIVE: To evaluate the association between baseline characteristics, three
physical performance tests and fall history in a sample of the elderly from
Korean population. METHODS: A total of 307 participants (mean age, 76.70+/-4.85
years) were categorized into one of two groups, i.e., fallers and non-fallers.
Fifty-two participants who had reported falling unexpectedly at least once in the
previous 12 months were assigned to the fallers group. Physical performance tests
included Short Physical Performance Battery (SPPB), Berg Balance Scale (BBS),
Timed Up and Go test. The differences between the two study groups were compared
and we analyzed the correlations between fall histories and physical performance
tests. RESULTS: SPPB demonstrated a significant association with fall history.
Although the BBS total scores did not show statistical significance, two dynamic
balance test items of BBS (B12 and B13) showed a significant association among
fallers. CONCLUSION: This study suggests that SPPB and two dynamic balance test
items of the BBS can be used in screening for risk of falls in an ambulatory
elderly population.
PMID- 28503458
TI - Quality of Life and Awareness of Cardiac Rehabilitation Program in People With
Cardiovascular Diseases.
AB - OBJECTIVE: To evaluate the level of health-related quality of life (HRQoL), life
satisfaction, and their present awareness of cardiac rehabilitation (CR) program
in people with cardiovascular diseases. METHODS: A questionnaire survey was
completed by 53 patients (mean age, 65.7+/-11.6 years; 33 men and 20 women) with
unstable angina, myocardial infarction, or heart failure. The questionnaire
included the Medical Outcome Study 36-item Short-Form Health Survey (MOS SF-36),
life domain satisfaction measure (LDSM), and the awareness and degree of using CR
program. RESULTS: The average scores of physical component summary (PCS) and
mental component summary (MCS) were 47.7+/-18.5 and 56.5+/-19.5, respectively.
There were significant differences in physical role (F=4.2, p=0.02), vitality
(F=10.7, p<0.001), mental health (F=15.9, p<0.001), PCS (F=3.6, p=0.034), and MCS
(F=11.9, p<0.001) between disease types. The average LDSM score was 4.7+/-1.5.
Age and disease duration were negatively correlated with multiple HRQoL areas
(p<0.05). Monthly income, ejection fraction, and LDSM were positively correlated
with several MOS SF-36 factors (p<0.05). However, the number of modifiable risk
factors had no significant correlation with medication. Thirty-seven subjects
(69.8%) answered that they had not previously heard about CR program. Seventeen
patients (32.1%) reported that they were actively participating in CR program.
Most people said that a reasonable cost of CR was less than 100,000 Korean won
per month. CONCLUSION: CR should focus on improving the physical components of
quality of life. In addition, physicians should actively promote CR to
cardiovascular disease patients to expand the reach of CR program.
PMID- 28503459
TI - Changes in Resting Calcaneal Stance Position Angle Following Insole Fitting in
Children With Flexible Flatfoot.
AB - OBJECTIVE: To clarify the relationship of the initial radiologic and a
biomechanical parameter at first clinical visit, and define the effectiveness of
modified insole, following insole fitting in children with flexible flatfoot.
METHODS: Children aged less than 13 years with flexible flatfoot were enrolled.
The total number of subjects was 66 (33 boys, 33 girls). The subjects were
divided into 5 subgroups, based on age: 1-2, 3-4, 5-6, 7-9, and 10-12 years. The
mean time period between the initial & final examination for their resting
calcaneal stance position angle (RCSPA) was 24 months. Radiography quantified the
deformity by measuring angles, including the talometatarsal angle, the metatarsal
angle, and the calcaneal pitch angle. RESULTS: From the angles measured on
radiographs, only the talometatarsal angle showed a statistically significant
correlation to the initial RCSPA (r=-0.578 for right side, r=-0.524 for left
side; p<0.01). The mean RCSPA improved in all subgroups of subjects following
insole fitting. Moreover, in children younger than 7 years, the improvement in
RCSPA from the insole fitting was greater compared to children aged 7 years and
older. CONCLUSION: The insole has additionally beneficial effects in all
populations younger than 13 years. However, there might exist a hidden effect of
normal structural pedal alignment during growth accompanied with bony maturation
and developmental process. To date, it is controversial whether the treatment of
flexible flatfoot is necessary in the vast majority of cases, or simple
observation and advice to parents would suffice.
PMID- 28503460
TI - Relationship Between Mobility and Self-Care Activity in Children With Cerebral
Palsy.
AB - OBJECTIVE: To investigate the factors influencing the development of self-care
activity, and the association between mobility and self-care activity in children
with cerebral palsy (CP). METHODS: A total of 63 CP children aged >=4 years, were
studied retrospectively. Children with severe intellectual disability or
behavioral problems were excluded. The relationship between the Gross Motor
Function Classification System (GMFCS), the Manual Ability Classification System
(MACS), and the Pediatric Evaluation of Disability Inventory (PEDI) was analyzed.
Simple and multiple linear regression analyses were conducted for continuous
variables, such as verbal intelligence quotient (IQ) and PEDI subscales. RESULTS:
Final evaluation was done for 25 children, ranging from 4 to 11 years of age.
According to GMFCS levels, the differences in PEDI-self-care scores, showed
statistically borderline significance (p=0.051). Conversely, differences in PEDI
self-care scores according to CP types and MACS levels were not statistically
significant. Simple linear regression analysis showed that PEDI mobility and PEDI
social function significantly influence the PEDI self-care. Multiple linear
regression analysis showed that PEDI mobility was the only factor significantly
influencing PEDI self-care in children aged >=7 years (R2=0.875, p=0.03).
CONCLUSION: Mobility is important for the acquisition of self-care abilities in
children with CP aged >=7 years.
PMID- 28503461
TI - Immediate Effect of a Single Session of Whole Body Vibration on Spasticity in
Children With Cerebral Palsy.
AB - OBJECTIVE: To investigate the immediate effect of a single session of whole body
vibration (WBV) on lower extremity spasticity in children with cerebral palsy
(CP). METHODS: Seventeen children with spastic CP were included. A single session
of WBV was administered: 10-minute WBV, 1-minute rest, and 10-minute WBV. The
effects of WBV were clinically assessed with the Modified Ashworth Scale (MAS)
and Modified Tardieu Scale (MTS) before and immediately, 30 minutes, 1 hour, 2
hours, 3 hours, and 4 hours after WBV. RESULTS: Spasticity of the ankle
plantarflexor, as assessed by MAS and MTS scores, was reduced after WBV. Post-hoc
analysis demonstrated that, compared to baseline, the MAS significantly improved
for a period of 1 hour after WBV, and the R1 and R2-R1 of the MTS significantly
improved for a period of 2 hours after WBV. CONCLUSION: A single session of WBV
improves spasticity of ankle plantarflexors for 1-2 hours in children with CP.
Future studies are needed to test whether WBV is an effective preparation before
physiotherapy and occupational therapy.
PMID- 28503462
TI - Predictors for Depressive Mood in Geriatric Patients After Traumatic Brain
Injury: A Retrospective Cross-Sectional Study.
AB - OBJECTIVE: To identify predictors for depressive mood in geriatric patients after
traumatic brain injury (TBI). METHODS: A retrospective review of patients'
medical charts was performed in TBI patients who were older than 60 years and
referred to the Department of Rehabilitation Medicine at Severance Hospital in
2002-2016. The patients were classified into two groups based on the Geriatric
Depression Scale (GDS): non-depressive group (0<=GDS<=16) and depressive group
(17<=GDS<=30). Data was collected on demographic, socioeconomic, comorbidities,
and trauma-related factors, as well as the pathophysiology of TBI, localization
of lesion, post-traumatic complications, functional level, and cognitive and
linguistic function. Significant variables from univariate analysis were analyzed
using logistic regression. RESULTS: Forty-two patients were included, of whom
64.3% displayed a depressive mood. Patients in the depressive group had higher
comorbidity scores (p=0.03), lower Functional Independence Measure (FIM) totals
(p=0.03) and FIM motor (p=0.03) scores, higher modified Rankin Scale scores
(p=0.04), and frequently had a bilateral or left side brain lesion (p=0.002).
Higher comorbidity scores (odds ratio [OR], 1.764; 95% confidence interval [CI],
1.047-2.971), bilateral lesions (OR, 13.078; 95% CI, 1.786-95.780), and left side
lesions (OR, 46.074; 95% CI, 3.175-668.502) were independently associated with a
depressive mood in the multiple logistic regression analysis. CONCLUSION: The
risk of depressive mood in geriatric patients after TBI is associated with
comorbidity, functional limitation, and the horizontal distribution of brain
lesions. The most significant determining factors were comorbidity and the
horizontal distribution of brain lesions. Early detection of risk factors is
important to prevent and manage depressive mood in geriatric patients after TBI.
PMID- 28503463
TI - Optimal Radial Motor Nerve Conduction Study Using Ultrasound in Healthy Adults.
AB - OBJECTIVE: To obtain reference values, to suggest optimal recording and
stimulation site for radial motor nerve conduction study (RmNCS), and to analyze
the correlation among RmNCS parameters, demographics and ultrasonography (US)
findings. METHODS: A total of 55 volunteers participated in this study. We
hypothesized that 'lateral edge of spiral groove (A)' was the optimal stimulation
site, and the 'largest cross-sectional area (CSA) of extensor indicis proprius
(EIP) muscle (B)' was the optimal recording site. The surface distance between
'A' and the lateral epicondyle of the humerus divided by upper arm length, was
named the spiral groove ratio. The surface distance between 'B' and the ulnar
styloid process divided by forearm length, was named the EIP ratio. Using US, we
identified these sites, and further conducted RmNCS. RESULTS: Data was collected
from 100 arms of the 55 volunteers. Mean amplitude and latency were 5.7+/-1.1 mV
and 5.7+/-0.5 ms, respectively, at the spiral groove, and velocity between elbow
and spiral groove was 73.7+/-7.0 m/s. RmNCS parameters correlated significantly
with height, weight, arm length, and CSA of the EIP muscle. Spiral groove ratio
and EIP ratio were 0.338+/-0.03 and 0.201+/-0.03, respectively; both values were
almost the same, regardless of age, sex and handedness. CONCLUSION: We
established a reference value and standardized method of RmNCS using US. Optimal
RmNCS can be conducted by placing the recording electrode 20% (about one-fifth)
of forearm length from the ulnar styloid process, and stimulating at 34% (about
one-third) of the humeral length from the lateral epicondyle.
PMID- 28503464
TI - Maximal Inspiratory Pressure and Maximal Expiratory Pressure in Healthy Korean
Children.
AB - OBJECTIVE: To evaluate respiratory muscle strength in healthy Korean children in
order to establish the criteria for normal reference values for future
applications. In contrast with the other parameters for testing pulmonary
function, normal values for respiratory muscle strength in healthy Korean
children have not been assessed to date. METHODS: We conducted a complete survey
of 263 students at Sinmyung Elementary School in Yangsan, Gyeongsangnam-do, and
measured their height and body weight, performed pulmonary function tests, and
evaluated maximal inspiratory pressure (MIP) and maximal expiratory pressure
(MEP) as measures of respiratory muscle strength. We excluded the subjects with
respiratory or cardiovascular diseases that could affect the results. The
subjects were children aged 8-12 years, and they consisted of 124 boys and 139
girls. RESULTS: The MIP and MEP values (mean+/-standard deviation) for the entire
subject group were 48.46+/-18.1 cmH2O and 47.95+/-16 cmH2O, respectively. Boys
showed higher mean values for MIP and MEP in every age group. Korean children
showed lower mean values for MIP and MEP compared to those in previous studies
conducted in other countries (Brazil and USA). CONCLUSION: Our results showed
that boys generally have greater respiratory muscle strength than girls. We found
a significant difference between the results of our study and those of previous
studies from other countries. We speculate that this may be attributed to
differences in ethnicity, nutrition, or daily activities.
PMID- 28503465
TI - Correlation of Serum Creatine Kinase Level With Pulmonary Function in Duchenne
Muscular Dystrophy.
AB - OBJECTIVE: To investigate the relationship between serum creatine kinase (CK)
level and pulmonary function in Duchenne muscular dystrophy (DMD). METHODS: A
total of 202 patients with DMD admitted to the Department of Rehabilitation
Medicine, Gangnam Severance Hospital were enrolled from January 1, 1999 to March
31, 2015. Seventeen patients were excluded. Data collected from the 185 patients
included age, height, weight, body mass index, pulmonary function tests including
forced vital capacity (FVC), peak cough flow, maximal expiratory pressure (MEP),
and maximal inspiratory pressure (MIP), and laboratory measurements (serum level
of CK, CK-MB, troponin-T, and B-type natriuretic peptide). FVC, MEP, and MIP were
expressed as percentages of predicted normal values. RESULTS: Serum CK activities
were elevated above normal levels, even in the oldest DMD group. Serum CK level
was strongly correlated with pulmonary functions of sitting FVC (p<0.001), supine
FVC (p<0.001), MIP (p=0.004), and MEP (p<0.001). CONCLUSION: Serum CK level is a
reliable screening test even in patients with advanced DMD, and is a strong
predictor of pulmonary functions.
PMID- 28503466
TI - Sonographic Findings of Polyneuropathy Associated With Cerebrotendinous
Xanthomatosis: A Case Report.
AB - Cerebrotendinous xanthomatosis is a rare autosomal recessive disease that
involves multiple organs, including the peripheral nervous system. The present
study is the first to report the ultrasonographic findings of peripheral nerves
in a patient with cerebrotendinous xanthomatosis. The patient presented with
bilateral Achilles tendon enlargement and foot hypesthesia. Sonographic
examination revealed hypoechoic, swollen peripheral nerves with enlarged
bilateral Achilles tendons. Since the ultrasonographic findings revealed
peripheral involvement, the diagnosis of cerebrotendinous xanthomatosis was
established after laboratory and genetic studies along with clinical findings.
PMID- 28503468
TI - Extravasation of the Contrast Material During Voiding Cystourethrography in a
Chronic Spinal Cord Injury Patient: A Case Report.
AB - Neurogenic bladder is common in most spinal cord injury patients. Voiding
cystourethrography (VCUG) is recommended in these patients to detect urinary
tract complications. However, rare but serious complications may occur during
VCUG, although VCUG is generally safe. There are several case reports of bladder
rupture occurring in pediatric patients. Here, we report the first case of
iatrogenic bladder rupture in an adult spinal cord injury patient in Korea.
Particularly, extravasation of contrast without manual instillation has hardly
ever been reported. To the best of our knowledge, this is the first reported case
of bladder rupture without manual instillation during VCUG. We report a case of a
59-year-old female with paraplegia due to tuberculous spondylitis who underwent
VCUG as a part of routine evaluation of neurogenic bladder. Extravasation of the
contrast media during VCUG developed as a complication and the patient recovered
spontaneously without any intervention. Therefore, VCUG should be performed
properly in chronic spinal cord injury patients.
PMID- 28503467
TI - Medial Lemniscus Tract Lesion After High Voltage Electrical Injury: A Case
Report.
AB - We present the case of a 33-year-old man who experienced a 10,000-V electrical
shock when working with electrical wiring. He suffered third-degree burns on his
scalp at the right occiput (entry wound) and on his left arm (exit would), and a
second-degree burn on his left foot (exit wound). He presented with severe
spasticity of both lower extremities, motor weakness with a Medical Research
Council grade of 3, and sensory impairments below thoracic level 11 that included
an inability to sense light touch and defects in proprioception. Initial magnetic
resonance imaging (MRI) scans of his spine and brain showed no definite
abnormalities. However, tractography obtained by diffusion tensor imaging of the
brain showed absence of the right medial lemniscus tract. A cervical MRI scan 1
month later showed spinal cord swelling from cervical 1-5 levels, and signal
changes in the lateral and posterior white matter in the axial view. After 6
months of rehabilitation, he recovered almost normal degree of motor function in
his lower extremities and disappearance of spasticity. However, since the sensory
impairments persisted, especially defects in proprioception, he was unable to
walk independently.
PMID- 28503469
TI - Motor Neuron Disease Presenting With Acute Respiratory Failure: A Case Study.
AB - Motor neuron diseases (MNDs) refer to a heterogeneous group of progressive
neurologic disorders caused by degeneration of motor neurons. The diseases affect
either the upper motor neurons, lower motor neurons, or both, and are
characterized by weakness, atrophy, fasciculation, spasticity, and respiratory
failure. We report a case of a 61-year-old male patient with no past history of
cardiovascular or pulmonary disease, who presented with only dyspnea, and no
indication of any other symptom such as muscle weakness, atrophy, or bulbar
dysfunction. Neuromuscular conduction study, including a study of the phrenic
nerve, confirmed the diagnosis of MND. The patient greatly improved giving
respiratory assistance at night, using a noninvasive ventilator. This case
indicates that MNDs should be considered as differential diagnoses for patients
showing acute respiratory failure of unknown causes. This report will aid in the
prompt diagnosis and treatment of MNDs.
PMID- 28503470
TI - Falsely Elevated Postvoid Residual Urine Volume in Uterine Myoma.
AB - Precise measurement of postvoid residual (PVR) urine volume is a key factor in
assessing patients with voiding dysfunction, including those with lower urinary
tract problems. The safe and noninvasive ultrasound bladder scan is the preferred
mode to measure PVR volume. However, this procedure has a false-positive rate up
to 9%, in the presence of ovarian cysts, renal cysts, ascites, or uterine myoma
with cystic degeneration. Until now, cystic lesions are known to cause false
positivity in ultrasound bladder scanner. However, we encountered falsely
elevated PVR in two cases of non-cystic uterine myomas. We present these cases
with detailed radiologic images and volume measurement data.
PMID- 28503471
TI - Correction: Effectiveness of Lower Energy Density Extracorporeal Shock Wave
Therapy in the Early Stage of Avascular Necrosis of the Femoral Head.
AB - [This corrects the article on p. 871 in vol. 40, PMID: 27847717.].
PMID- 28503472
TI - Recognition and management of palatogingival groove for tooth survival: a
literature review.
AB - Palatogingival groove (PGG) is an anomaly in the maxillary anterior teeth, often
accompanied by the area of bony destruction adjacent to the teeth with no carious
or traumatic history. The hidden trap in the tooth can harbor plaque and
bacteria, resulting in periodontal destruction with or without pulpal pathologic
change. Related diseases can involve periodontal destruction, combined endodontic
periodontal lesions, or separate endodontic and periodontal lesions. Disease
severity and prognosis related to PGG depend on several factors, including
location, range, depth, and type of the groove. Several materials have been used
and recommended for cases of extensive periodontal destruction from PGG to remove
and block the inflammatory source and recover the health of surrounding
periodontal tissues. Even in cases of severe periodontal destruction, several
studies have reported favorable treatment outcomes with proper management. With
new options in diagnosis and treatment, clinicians need a detailed understanding
of the characteristics, treatment, and prognosis of PGG to successfully manage
the condition.
PMID- 28503473
TI - Analysis of the shelf life of chitosan stored in different types of packaging,
using colorimetry and dentin microhardness.
AB - OBJECTIVES: Chitosan has been widely investigated and used. However, the
literature does not refer to the shelf life of this solution. This study
evaluated, through the colorimetric titration technique and an analysis of dentin
micro-hardness, the shelf life of 0.2% chitosan solution. MATERIALS AND METHODS:
Thirty human canines were sectioned, and specimens were obtained from the second
and third slices, from cemento-enamel junction to the apex. A 0.2% chitosan
solution was prepared and distributed in 3 identical glass bottles (v1, v2, and
v3) and 3 plastic bottles (p1, p2, and p3). At 0, 7, 15, 30, 45, 60, 90, 120,
150, and 180 days, the specimens were immersed in each solution for 5 minutes (n
= 3 each). The chelating effect of the solution was assessed by micro-hardness
and colorimetric analysis of the dentin specimens. 17% EDTA and distilled water
were used as controls. Data were analyzed statistically by two-way and Tukey
Kramer multiple comparison (alpha = 0.05). RESULTS: There was no statistically
significant difference among the solutions with respect to the study time (p =
0.113) and micro-hardness/time interaction (p = 0.329). Chitosan solutions and
EDTA reduced the micro-hardness in a similar manner and differed significantly
from the control group (p < 0.001). Chitosan solutions chelated calcium ions
throughout the entire experiment. CONCLUSIONS: Regardless of the storage form,
chitosan demonstrates a chelating property for a minimum period of 6 months.
PMID- 28503474
TI - Bonding of the silane containing multi-mode universal adhesive for lithium
disilicate ceramics.
AB - OBJECTIVES: This study evaluated the influence of a multi-mode universal adhesive
(MUA) containing silane (Single Bond Universal, 3M EPSE) on the bonding of resin
cement to lithium disilicate. MATERIALS AND METHODS: Thirty IPS e.max CAD
specimens (Ivoclar Vivadent) were fabricated. The surfaces were treated as
follows: Group A, adhesive that did not contain silane (ANS, Porcelain Bonding
Resin, Bisco); Group B, silane (S) and ANS; Group C, hydrofluoric acid (HF), S,
and ANS; Group D, MUA; Group E, HF and MUA. Dual-cure resin cement (NX3, Kerr)
was applied and composite resin cylinders of 0.8 mm in diameter were placed on it
before light polymerization. Bonded specimens were stored in water for 24 hours
or underwent a 10,000 thermocycling process prior to microshear bond strength
testing. The data were analyzed using multivariate analysis of variance (p <
0.05). RESULTS: Bond strength varied significantly among the groups (p < 0.05),
except for Groups A and D. Group C showed the highest initial bond strength (27.1
+/- 6.9 MPa), followed by Group E, Group B, Group D, and Group A. Thermocycling
significantly reduced bond strength in Groups B, C, and E (p < 0.05). Bond
strength in Group C was the highest regardless of the storage conditions (p <
0.05). CONCLUSIONS: Surface treatment of lithium disilicate using HF and silane
increased the bond strength of resin cement. However, after thermocycling, the
silane in MUA did not help achieve durable bond strength between lithium
disilicate and resin cement, even when HF was applied.
PMID- 28503475
TI - The use of auxiliary devices during irrigation to increase the cleaning ability
of a chelating agent.
AB - OBJECTIVES: This study investigated the cleaning ability of ultrasonically
activated irrigation (UAI) and a novel activation system with reciprocating
motion (EC, EasyClean, Easy Equipamentos Odontologicos) when used with a
relatively new chelating agent (QMix, Dentsply). In addition, the effect of QMix
solution when used for a shorter (1 minute) and a longer application time (3
minutes) was investigated. MATERIALS AND METHODS: Fifty permanent human teeth
were prepared with K3 rotary system and 6% sodium hypochlorite. Samples were
randomly assigned to five groups (n = 10) according to the final irrigation
protocol: G1, negative control (distilled water); G2, positive control (QMix 1
minute); G3, QMix 1 minute/UAI; G4, QMix 1 minute/EC; G5, QMix 3 minutes.
Subsequently the teeth were prepared and three photomicrographs were obtained in
each root third of root walls, by scanning electron microscopy. Two blinded and
pre-calibrated examiners evaluated the images using a four-category scoring
system. Data were statistically analyzed using Kruskal-Wallis and Dunn tests (p <
0.05). RESULTS: There were differences among groups (p < 0.05). UAI showed better
cleaning ability than EC (p < 0.05). There were improvements when QMix was used
with auxiliary devices in comparison with conventional irrigation (p < 0.05).
Conventional irrigation for 3 minutes presented significantly better results than
its use for 1 minute (p < 0.05). CONCLUSIONS: QMix should be used for 1 minute
when it is used with UAI, since this final irrigation protocol showed the best
performance and also allowed clinical optimization of this procedure.
PMID- 28503476
TI - Differential diagnosis of periapical cyst using collagen birefringence pattern of
the cyst wall.
AB - OBJECTIVES: Periapical lesions, including periapical cyst (PC), periapical
granuloma (PG), and periapical abscess (PA), are frequently affected by
chemical/physical damage during root canal treatment or severe bacterial
infection, and thus, the differential diagnosis of periapical lesions may be
difficult due to the presence of severe inflammatory reaction. The aim of this
study was to make differential diagnosis among PC, PG, and PA under polarizing
microscope. MATERIALS AND METHODS: The collagen birefringence patterns of 319
cases of PC (n = 122), PG (n = 158), and PA (n = 39) obtained using a polarizing
microscope were compared. In addition, 6 cases of periodontal fibroma (PF) were
used as positive controls. RESULTS: Collagen birefringence was condensed with a
thick, linear band-like pattern in PC, but was short and irregularly scattered in
PG, and scarce or absent in PA. PF showed intense collagen birefringence with a
short, palisading pattern but no continuous band-like pattern. The linear band
like birefringence in PC was ascribed to pre-existing expansile tensile stress of
the cyst wall. CONCLUSIONS: In this study all PCs (n = 122) were distinguishable
from PGs and PAs by their characteristic birefringence, despite the absence of
lining epithelium (n = 20). Therefore, the authors suggest that the presence of
linear band-like collagen birefringence of the cyst wall aids the diagnostic
differentiation of PC from PG and PA.
PMID- 28503478
TI - The effects of non-thermal plasma and conventional treatments on the bond
strength of fiber posts to resin cement.
AB - OBJECTIVES: This study compared the effect of hexamethyldisiloxane (HMDSO) and
ammonia (NH3) plasmas on the bond strength of resin cement to fiber posts with
conventional treatments. MATERIALS AND METHODS: Sixty-five fiber posts were
divided into 5 groups: Control (no surface treatment); H2O2 (24% hydrogen
peroxide for 1 min); Blasting (blasting with aluminum oxide for 30 sec); NH3 (NH3
plasma treatment for 3 min); HMDSO (HMDSO plasma treatment for 15 min). After the
treatments, the Ambar adhesive (FGM Dental Products) was applied to the post
surface (n = 10). The fiber post was inserted into a silicon matrix that was
filled with the conventional resin cement Allcem Core (FGM). Afterwards, the
post/cement specimens were cut into discs and subjected to a push-out bond
strength (POBS) test. Additionally, 3 posts in each group were evaluated using
scanning electron microscopy. The POBS data were analyzed by one-way analysis of
variance and the Tukey's honest significant difference post hoc test (alpha =
0.05). RESULTS: The Blasting and NH3 groups showed the highest POBS values. The
HMDSO group showed intermediate POBS values, whereas the Control and H2O2 groups
showed the lowest POBS values. CONCLUSION: Blasting and NH3 plasma treatments
were associated with stronger bonding of the conventional resin cement Allcem to
fiber posts, in a procedure in which the Ambar adhesive was used.
PMID- 28503477
TI - Color stability of bulk-fill and incremental-fill resin-based composites polished
with aluminum-oxide impregnated disks.
AB - OBJECTIVES: This study aimed to evaluate the color stability of bulk-fill and
nanohybrid resin-based composites polished with 3 different, multistep, aluminum
oxide impregnated finishing and polishing disks. MATERIALS AND METHODS: Disk
shaped specimens (8 mm in diameter and 4 mm in thickness) were light-cured
between two glass slabs using one nanohybid bulk-fill (Tetric EvoCeram, Ivoclar
Vivadent), one micro-hybrid bulk-fill (Quixfil, Dentsply), and two nanohybrid
incremental-fill (Filtek Ultimate, 3M ESPE; Herculite XRV Ultra, Kerr) resin
based composites, and aged by thermocycling (between 5 - 55C, 3,000 cycles).
Then, they were divided into subgroups according to the polishing procedure as
SwissFlex (Coltene/Whaledent), Optidisc (Kerr), and Praxis TDV (TDV Dental) (n =
12 per subgroup). One surface of each specimen was left unpolished. All specimens
were immersed in coffee solution at 37C. The color differences (DeltaE) were
measured after 1 and 7 days of storage using a colorimeter based on CIE Lab
system. The data were analyzed by univariate ANOVA, Mann-Whitney U test, and
Friedmann tests (alpha = 0.05). RESULTS: Univariate ANOVA detected significant
interactions between polishing procedure and composite resin and polishing
procedure and storage time (p < 0.05). Significant color changes were detected
after 1 day storage in coffee solution (p < 0.05), except Quixfil/Optidisc which
was color-stable after 7 days (p > 0.05). Polishing reduced the discoloration
resistance of Tetric EvoCeram/SwissFlex, Tetric EvoCeram/Praxis TDV, Quixfil
SwissFlex, and all Herculite XRV Ultra groups after 7 days storage (p < 0.05).
CONCLUSIONS: Discoloration resistance of bulk-fill resin-based composites can be
significantly affected by the polishing procedures.
PMID- 28503479
TI - Cyclic fatigue life of Tango-Endo, WaveOne GOLD, and Reciproc NiTi instruments.
AB - OBJECTIVES: To compare the fatigue life of Tango-Endo, WaveOne GOLD, and Reciproc
NiTi instruments under static model via artificial canals with different angles
of curvature. MATERIALS AND METHODS: Reciproc R25, WaveOne GOLD Primary, and
Tango-Endo instruments were included in this study (n = 20). All the instruments
were rotated in artificial canals which were made of stainless steel with an
inner diameter of 1.5 mm, 45 degrees , 60 degrees , and 90 degrees angles of
curvatures and a radius of curvature of 5 mm until fracture occurred, and the
time to fracture was recorded in seconds using a digital chronometer. The data
were analyzed using Kruskal-Wallis and post-hoc Dunn tests were used for the
statistical analysis of data in SPSS 21.0 software. RESULTS: Tango-Endo files
were found to have significantly higher values than WaveOne GOLD and Reciproc
files in terms of fatigue life (p < 0.05). However, there was no statistically
significant difference between fatigue life of Reciproc and WaveOne GOLD files (p
> 0.05). It was determined that increasing the angle of curvature of the
stainless canals caused significant decreases in fatigue life of all of three
files (p < 0.05). CONCLUSIONS: Within the limitations of the present study, the
cyclic fatigue life of Tango-Endo in canals having different angles of curvature
was statistically higher than Reciproc and WaveOne GOLD.
PMID- 28503480
TI - Intraoperative discomfort associated with the use of a rotary or reciprocating
system: a prospective randomized clinical trial.
AB - OBJECTIVES: The aim of this randomized, controlled, prospective clinical study
was to evaluate patients' intraoperative discomfort during root canal
preparations in which either multi-file rotary (Mtwo) or single-file
reciprocating (Reciproc) systems were used. MATERIALS AND METHODS: Fifty-five
adult patients, aged between 25 and 69 years old, with irreversible pulpitis or
pulp necrosis participated in this study. Either the mesiobuccal or the
distobuccal canals for maxillary molars and either the mesiobuccal or the
mesiolingual canals for mandibular molars were randomly chosen to be instrumented
with Mtwo multi-file rotary or Reciproc single-file reciprocating systems.
Immediately after each canal instrumentation under anesthesia, patient discomfort
was assessed using a 1 - 10 visual analog scale (VAS), ranging from 'least
possible discomfort' (1) to 'greatest possible discomfort' (10). The Wilcoxon
signed-rank test was used to determine significant differences at p< 0.05.
RESULTS: Little intraoperative discomfort was found in all cases. No
statistically significant differences in intraoperative discomfort between the 2
systems were found (p = 0.660). CONCLUSIONS: Root canal preparation with multi
file rotary or single-file reciprocating systems had similar and minimal effects
on patients' intraoperative discomfort.
PMID- 28503482
TI - Statistical notes for clinical researchers: Chi-squared test and Fisher's exact
test.
PMID- 28503481
TI - Dental management of patients with X-linked hypophosphatemia.
AB - X-linked hypophosphatemia (XLH) is a hereditary metabolic disease caused by the
loss of phosphate through the renal tubules into the urine, and an associated
decrease in serum calcium and potassium phosphate. Its dental features include
spontaneous dental abscesses that occur in the absence of trauma or dental
caries. The aim of this case report was to describe the dental problems of XLH
patients and to evaluate limitations in their treatment. A 14 year old male and a
38 year old female with XLH were referred to the Department of Conservative
Dentistry for endodontic treatment. The dental findings were periapical abscesses
without obvious trauma or caries. Conservative endodontic treatment was performed
in teeth with pulp necrosis and abscess. In case 1, the treated teeth showed
improvements in bone healing, without clinical symptoms. However, in case 2, the
implants and the treated tooth showed hypermobility, and the final restoration
was therefore postponed. Early diagnosis, periodic examinations, and
communication with the patient's pediatrician are important in the dental
management of patients with XLH.
PMID- 28503483
TI - Importance of Hematoma Removal Ratio in Ruptured Middle Cerebral Artery Aneurysm
Surgery with Intrasylvian Hematoma.
AB - OBJECTIVE: Ruptured middle cerebral artery (MCA) aneurysm with intrasylvian
hematoma usually accompanied by progressive cerebral swelling with poorer
outcomes. The authors present characteristics and importance of intrasylvian
hematoma removal in the aneurysm surgery. MATERIALS AND METHODS: From 2012
February to 2014 March, 24 aneurysm surgeries for ruptured MCA aneurysms with
intrasylvian hematoma were performed in the authors' clinic. The patients were
classified according to three groups. Group A included patients who underwent
decompressive craniectomy within a few days after aneurysm surgery due to
progressive cerebral swelling, group B included patients for whom decompression
was not necessary, and group C included patients who showed severe cerebral
swelling on admission and decompressive craniectomy and aneurysm surgery in one
stage. RESULTS: The mean hematoma volume on admission was 28.56 mL, 24.96 mL, and
66.78 mL for groups A, B and C, respectively. Removal of a larger amount of
hematoma was observed on postoperative computerized tomography scan in groups B
and C (63.2% and 59.0%) compared with group A (33.4%). Although no statistical
difference was found between group A and group B (p = 0.115), it tends to show
the lesser amount of hematoma removed, the more likely cerebral swelling will
progress. CONCLUSION: The lesser amount of hematoma in ruptured MCA aneurysm with
intrasylvian hematoma tends to show benign clinical course than larger amounts.
But, even if the hematoma is not easily removed in the operation, we suggest the
other procedures such as continuous external catheter drainage of hematoma to
avoid unnecessary coagulation or brain retraction.
PMID- 28503484
TI - Prophylactic Dual Catheter Technique to Prevent Side Branch Snowplowing
Complications during Angioplasty and Stenting.
AB - OBJECTIVE: Angioplasty and Stenting of intracranial atherosclerotic lesions have
a higher complication rate and a large proportion of this is attributable to side
branch arterial occlusion from forceful displacement of the atheroma into the
ostia or snowplowing effect. This can result in severe disabilities when it
result in small infarcts involving eloquent areas in the posterior circulation or
the motor tracts. MATERIALS AND METHODS: We present a series of 6 cases utilizing
a new dual catheter technique for maintaining the patency of at-risk vessels
during angioplasty and stenting. There are several methods previously described
to help reduce the incidence of stroke but because they do not have a physical
presence in the ostia to protect it, they are unable to guarantee the patency of
the vessel. RESULTS: All 6 patients underwent angioplasty and stenting with the
technique. The patients were assessed for complications with post-procedure
magnetic resonance imaging and no complications were found. CONCLUSION: In this
preliminary series, the dual catheter technique appears to safe and effective in
preventing occlusion of the adjacent branch arteries. This technique may
facilitate the use of the Wingspan stent in the treatment of intracranial
atherosclerotic stenotic segments by reducing the risk of peri-procedural stroke.
PMID- 28503487
TI - Discrepancy between Angiography and Operative Findings of Small Side Wall
Aneurysms in Atherosclerotic Parent Arteries.
AB - Preoperative evaluation of precise aneurysmal geometry is important for the
treatment of intracranial aneurysms. We present two cases of unclippable side
wall aneurysms due to their extremely low dome height, which appeared as saccular
in the preoperative image because of a comparatively narrow atherosclerotic
parent arterial lumen. In both cases, a calcified vessel wall was noted
preoperatively. Lack of a definitive neck and abrupt discrepancy between the
fragile aneurysmal wall and the atherosclerotic parent arterial wall was
confirmed intraoperatively in both cases. This study describes an illustrative
mechanism for the finding with emphasis on the importance of its preoperative
diagnosis. Intracranial atherosclerosis associated with small side walled
aneurysms may lead to overestimation of aneurysm height on preoperative imaging
of the intravascular compartment.
PMID- 28503485
TI - Surgical Approaches for Symptomatic Cerebral Cavernous Malformations of the
Thalamus and Brainstem.
AB - OBJECTIVE: Surgical resection of thalamic and brainstem cerebral cavernous
malformations (CCMs) is associated with significant operative morbidity, but it
may be outweighed, in some cases, by the neurological damage from recurrent
hemorrhage in these eloquent areas. The goals of this retrospective cohort study
are to describe the technical nuances of surgical approaches and determine the
postoperative outcomes for CCMs of the thalamus and brainstem. MATERIALS AND
METHODS: We reviewed an institutional database of patients harboring thalamic or
brainstem CCMs, who underwent surgical resection from 2010 to 2014. The baseline
and follow-up neuroimaging and clinical findings of each patient and the
operative details of each case were evaluated. RESULTS: A total of eight
patients, including two with thalamic and six with brainstem CCMs, were included
in the study cohort. All patients had progressive neurological deterioration from
recurrent CCM hemorrhage, and the median modified Rankin Scale (mRS) at
presentation was 3. The median CCM maximum diameter and volume were 1.7 cm and
1.8 cm3, respectively. The thalamic CCMs were resected using the anterior
transcallosal transchoroidal and supracerebellar infratentorial approaches each
in one case (13%). The brainstem CCMs were resected using the retrosigmoid and
suboccipital trans-cerebellomedullary fissure approaches each in three cases
(38%). After a median follow-up of 11.5 months, all patients were neurologically
stable or improved, with a median mRS of 2. The rate of functional independence
(mRS 0-2) was 63%. CONCLUSION: Microneurosurgical techniques and approaches can
be safely and effectively employed for the management of thalamic and brainstem
CCMs in appropriately selected patients.
PMID- 28503486
TI - The Rupture Risk of Aneurysm in the Anterior Communicating Artery: A Single
Center Study.
AB - OBJECTIVE: The aim of this study was to evaluate the characteristics of ruptured
aneurysms at anterior communicating artery (A com) with an analysis of clinical
and morphological data, which could further our understanding of the risks of
ruptured A com aneurysms. MATERIALS AND METHODS: An analysis of data with 86
ruptured and 44 unruptured A com aneurysms were analyzed using a digital
subtraction angiography or 3-dimensional computed tomography angiography between
January 2010 and December 2015 in a single center. RESULTS: Fifty-five percent of
ruptured A com aneurysms were smaller than 4 mm in size. They had a smooth wall
(44%), with a mean size ratio of 4.22 (range: 0.7-14.3) and mean height/width
ratio of 1.48 (range: 0.5-2.9); 23 patients of A1 positive difference. Unruptured
aneurysms were mostly 2-10 mm in size (94%) and had an irregular wall (43%), with
a mean size ratio of 4.1 (range: 0.8-9.1) and mean height/width ratio of 1.2
(range: 0.1-2.6); 6 patients of A1 positive difference. In terms of the
morphology of aneurysms, size of A com, maximum aneurysm size, neck width,
aneurysm wall morphology, and size ratio were not different with statistical
significance. However, dominance of A1 (p = 0.01) and height/width ratio (p =
0.03) were found to be a significant predictive factor for rupture of A com
aneurysms. CONCLUSION: To better understand the rupture risk of A com aneurysms,
a large, multicenter, collaborative, and prospective study should be performed in
the future.
PMID- 28503488
TI - Treatment of Cerebral Vasospasm in an Infant Using a Modified Dotter Technique.
AB - An 8-month old female presented with spontaneous subarachnoid hemorrhage and was
treated successfully with endovascular coil embolization of the ruptured
aneurysm. Transcranial Doppler ultrasound performed four days later demonstrated
middle cerebral artery (MCA) velocities greater than 350 cm/sec on the right and
greater than 200 cm/sec on the left, despite medical management. The patient
demonstrated no focal neurological deficits, though examination was limited by
our patient's sedation and intubation. Angiography revealed severe vasospasm of
the supraclinoid internal carotid and MCA territories, bilaterally. The vasospasm
was refractory to the administration of intra-arterial verapamil. Balloon
angioplasty was attempted, but the device could not be advanced safely due to the
small size of the patient's vessels and the stiffness of the device. A
microcatheter (0.0165" diameter) was advanced over a J-shaped soft microwire
(0.014" diameter) to perform mechanical angioplasty in the internal carotid
artery and MCA vessels bilaterally. Dramatic improvement was seen
angiographically and on transcranial Doppler, and no complications were seen.
PMID- 28503489
TI - Spontaneous Absorption of Cerebral Air Emboli.
PMID- 28503491
TI - Variation in the Distribution of Putative Virulence and Colonization Factors in
Shiga Toxin-Producing Escherichia coli Isolated from Different Categories of
Cattle.
AB - Shiga toxin-producing Escherichia coli (STEC) are pathogens of significant public
health concern. Several studies have confirmed that cattle are the main reservoir
of STEC in Argentina and other countries. Although Shiga toxins represent the
primary virulence factors of STEC, the adherence and colonization of the gut are
also important in the pathogenesis of the bacteria. The aim of this study was to
analyze and to compare the presence of putative virulence factors codified in
plasmid -katP, espP, subA, stcE- and adhesins involved in colonization of cattle
efa1, iha- in 255 native STEC strains isolated from different categories of
cattle from different production systems. The most prevalent gene in all strains
was espP, and the less prevalent was stcE. katP was highly detected in strains
isolated from young and rearing calves (33.3%), while subA was predominant in
those isolated from adults (71.21%). Strains from young calves showed the highest
percentage of efa1 (72.46%), while iha showed a high distribution in strains from
rearing calves and adults (87.04 and 98.48% respectively). It was observed that
espP and iha were widely distributed throughout all strains, whereas katP, stcE,
and efa1 were more associated with the presence of eae and subA with the eae
negative strains. A great proportion of eae-negative strains were isolated from
adults -dairy and grazing farms- and from rearing calves -dairy and feedlot-,
while mostly of the eae-positive strains were isolated from dairy young calves.
Data exposed indicate a correlation between the category of the animal and the
production systems with the presence or absence of several genes implicated in
adherence and virulence of STEC.
PMID- 28503492
TI - Positive Effect of Probiotics on Constipation in Children: A Systematic Review
and Meta-Analysis of Six Randomized Controlled Trials.
AB - Context: Constipation in children is a prevalent, burdensome, and psychologically
important pediatric issue, the treatment of which remains a global challenge. The
use of probiotics has been reported for management of the gastrointestinal
microbiota. Objective: This study reviewed the existing literatures of 6
Randomized Control Trials (RCTs) to ascertain some baseline understanding and
available information for the effects of probiotics on stool frequency and
consistency in children with constipation. Data Sources: PubMed, Springer,
Elsevier Science, Cochrane Library, Scopus, Ovid (Medline, EMBASE, PsycINFO),
Orbis, and Web of Science from the earliest record in each database to 15
September, 2016. Study selection: Eligible studies were randomized controlled
trials that compared the effect of probiotics interventions to any control
intervention on stool frequency and consistency. Data Extraction: Studies were
identified by searching electronic databases. The meta-analysis was performed by
Review Manager 5.3 software using a randomized model. Results: Six studies were
identified. The use of probiotics significantly increased the stool frequency
[mean difference (MD), 0.73; 95% confidence interval (CI), 0.14-1.31; P = 0.02].
Subgroup assessment showed a significantly increased stool frequency in Asian
patients (MD, 1.18; 95% CI, 0.33-2.02; P = 0.006), but no significant difference
in stool consistency (MD, -0.07; 95% CI, -0.21-0.06; P = 0.27). Limitations: Only
six RCTs met the criteria and were included. Each RCT in this study was performed
in a different country, and some of the included studies had a small sample size,
which might have influenced the reliability and validity of the conclusions.
Conclusion: The present study shows that probiotics increase stool frequency and
have beneficial effects in Asian children. However, caution is needed when
interpreting these outcomes because of the existence of heterogeneity. Evidence
from larger samples and more adequately powered RCTs with results obtained by
standardized measurements are necessary to determine which species and dosage of
probiotics and what length of treatment are most efficacious for constipation in
children.
PMID- 28503493
TI - The Effect of Active Treatment and Visit Compared to Conventional Treatment, on
Preventing Recurrent Suicidal Attempts: A Randomized Controlled Clinical Trial.
AB - BACKGROUND: Suicide is a major problem, and its prevention is a global priority.
In many cases, suicide attempter attempts to do it again after the rescue. In
current study we aimed to compare active visit and treatment of patients in a
periodic manner with treatment as usual, in the prevention of recurrent suicidal
attempts. MATERIALS AND METHODS: This study was a randomized controlled clinical
trial which was conducted in Isfahan Noor Hospital's Emergency Center on 60
patients in 2013-2014. The samples were selected using simple random sampling and
they were assigned into two groups: The conventional treatment group (treatment
as usual) (30 patients), and visit and active treatment (30 patients). In the
intervention group, there were ten follow-ups by a face-to-face visit over 12
months, and six follow-ups by phone call in control group. Through the completion
of the initial and follow-up questionnaire evaluation was performed. The data
were analyzed using Cochran test, and repeated measure (ANOVA). RESULTS: During
the 12-month follow-up visit and active treatment, significant difference in
reducing suicidal thoughts (P = 0.003) was observed and an increase in the life
expectancy (P = 0.001), interest and motivation in life (P = 0.001) was found in
the intervention group, and also nonsignificant reduction was found in the rate
of suicidal attempts. CONCLUSION: Visit and active treatment is useful in suicide
attempters and it can helps in preventing recurrent suicide attempt as a
preventive program by increasing hope and reducing suicidal thoughts.
PMID- 28503490
TI - The Distinct Transcriptional Response of the Midgut of Amblyomma sculptum and
Amblyomma aureolatum Ticks to Rickettsia rickettsii Correlates to Their
Differences in Susceptibility to Infection.
AB - Rickettsia rickettsii is a tick-borne obligate intracellular bacterium that
causes Rocky Mountain Spotted Fever (RMSF). In Brazil, two species of ticks in
the genus Amblyomma, A. sculptum and A. aureolatum, are incriminated as vectors
of this bacterium. Importantly, these two species present remarkable differences
in susceptibility to R. rickettsii infection, where A. aureolatum is more
susceptible than A. sculptum. In the current study, A. aureolatum and A. sculptum
ticks were fed on suitable hosts previously inoculated with R. rickettsii,
mimicking a natural infection. As control, ticks were fed on non-infected
animals. Both midgut and salivary glands of all positively infected ticks were
colonized by R. rickettsii. We did not observe ticks with infection restricted to
midgut, suggesting that important factors for controlling rickettsial
colonization were produced in this organ. In order to identify such factors, the
total RNA extracted from the midgut (MG) was submitted to next generation RNA
sequencing (RNA-seq). The majority of the coding sequences (CDSs) of A. sculptum
differentially expressed by infection were upregulated, whereas most of modulated
CDSs of A. aureolatum were downregulated. The functional categories that comprise
upregulated CDSs of A. sculptum, for instance, metabolism, signal transduction,
protein modification, extracellular matrix, and immunity also include CDSs of A.
aureolatum that were downregulated by infection. This is the first study that
reports the effects of an experimental infection with the highly virulent R.
rickettsii on the gene expression of two natural tick vectors. The distinct
transcriptional profiles of MG of A. sculptum and A. aureolatum upon infection
stimulus strongly suggest that molecular factors in this organ are responsible
for delineating the susceptibility to R. rickettsii. Functional studies to
determine the role played by proteins encoded by differentially expressed CDSs in
the acquisition of R. rickettsii are warranted and may be considered as targets
for the development of strategies to control the tick-borne pathogens as well as
to control the tick vectors.
PMID- 28503494
TI - Intratumoral and Peritumoral Mast Cells in Malignant Melanoma: An
Immunohistochemical Study.
AB - BACKGROUND: The aim of the current study was to determine mast cell infiltration
in malignant melanoma by immunohistochemistry method and its relationship with
some of the cancer prognostic factors, including age, sex, and depth of the
tumor. MATERIALS AND METHODS: In this retrospective analytic cross-sectional
study, paraffin-embedded tissue blocks of patients with cutaneous malignant
melanoma who had undergone excisional biopsy were studied. Mast cells count in
studied cases in different stages of the tumor depth was evaluated by mast cell
tryptase immunohistochemistry method. Mast cells infiltration was evaluated both
inside the tumor and peritumoral area. Tumor infiltrating lymphocytes (TILs) was
also determined. Distribution of intratumoral and peritumoral mast cells and TILs
was compared in different stages tof tumor depth. RESULTS: In this study, 51
cases with melanoma were studied. Mean +/- standard deviation (SD) of
intratumoral mast cells in stages 1, 2, and 3 was 9.4 +/- 4.2, 10.8 +/- 5.1, and
2.1 +/- 2.3, respectively (P = 0.000). Mean +/- SD of peritumoral mast cells in
stages 1, 2 and 3 was 13.4 +/- 2.4, 16.6 +/- 2.4 and 8.2 +/- 4.6, respectively (P
= 0.000). There was a significant direct relationship between depth of the tumor
and TIL (P = 0.000) and distribution of intratumoral (P = 0.000) and peritumoral
mast cells (P = 0.000). CONCLUSION: Lower distribution of intratumoral and
peritumoral mast cells and TILs in higher stages of tumor depth in malignant
melanoma suggests a possible inhibitory effect of infiltrating mast cells and
lymphocytes on the progression of this tumor.
PMID- 28503495
TI - The Effects of Melatonin in Patients with Nonalcoholic Fatty Liver Disease: A
Randomized Controlled Trial.
AB - BACKGROUND: This study was designed to evaluate the effect of melatonin on
nonalcoholic fatty liver disease (NAFLD) in compared to placebo. MATERIALS AND
METHODS: A total of 100 patients with histopathological diagnosis NAFLD in two
groups of case and control received oral melatonin or placebo thrice daily for 3
months. Collected data were weight, waist, systolic blood pressure (SBP),
diastolic blood pressure (DBP), alanine aminotransferase (ALT), aspartate
aminotransferase (AST), high sensitive C-reactive protein (hsCRP), fatty liver
grade, and side effects which were measured at baseline and after treatment
period using standard clinical chemistry techniques. RESULTS: Before treatment
the mean of weight, waist, SBP, DBP, ALT, AST, and hsCRP between cases and
controls were similar (P > 0.5). After treatment, only the differences in the
mean of hsCRP in cases was significantly lower than controls (P = 0.003). In case
group, all variables after treatment were significantly decreased compare to
baseline (P > 0.5) and only AST after treatment was similar to before treatment
(P > 0.5). The mean of a decrease in the level of weight, waist, SBP, and ALT
were not statistically significant between groups (P > 0.5). In the case group in
compare to control group the level of DBP, AST, and hsCRP significantly more
decreased. After treatment fatty, liver grade was statistically improved in more
cases than controls (P = 0.001). Side effects were similar between the two
groups. CONCLUSION: Melatonin significantly decreases liver enzymes, so the use
of melatonin in patients with NAFLD can be effective.
PMID- 28503496
TI - Prevalence of Acquired Carbapenemase Genes in Klebsiella Pneumoniae by Multiplex
PCR in Isfahan.
AB - BACKGROUND: Multi-drug resistant Klebsiella pneumoniae has been considered as a
serious global threat. This study was done to investigate carbapenemase producing
genomes among K. pneumoniae isolates in Isfahan, Central Iran. MATERIALS AND
METHODS: In a cross-sectional study from 2011 to 2012, 29 carbapenem resistant
(according to disc diffusion method) carbapenemase producing (according to
modified Hodge test) K. pneumoniae strains were collected from Intensive Care
Unit (ICUs) of Al-Zahra referral Hospital. In the strains with the lack of
sensitivity to one or several carbapenems, beta-lactams, or beta-lactamases,
there has been performed modified Hodge test to investigate carbapenmase and then
only strains producing carbapenmases were selected for molecular methods.
RESULTS: In this study, there have been 29 cases of K. pneumoniae isolated from
hospitalized patients in the (ICU). Three cases (10.3%) contained blaVIM, 1 case
(3.4%) contained blaIMP, and 1 case (3.4%) contained blaOXA. The genes blaNDM and
blaKPC were not detected. Then, 16 cases (55.2%) from positive cases of K.
pneumoniae were related to the chip, 4 cases (13.8%) to catheter, 6 cases (20.7%)
to urine, and 3 cases (10.3%) to wound. CONCLUSION: It is necessary to monitor
the epidemiologic changes of these carbapenemase genes in K. pneumoniae in our
Hospital. More attention should be paid to nosocomial infection control measures.
Other carbapenemase producing genes should be investigated.
PMID- 28503497
TI - Investigation of Prognostic Factors and Survival without Recurrence in Patients
with Breast Cancer.
AB - BACKGROUND: One of the major consequences of breast cancer is the recurrence of
the disease. The objective of present study was to estimate the 7-year survival
without recurrence as well as the effective prognostic factors in recurrence.
MATERIALS AND METHODS: This historical cohort survival analysis was conducted on
1329 patients diagnosed with breast cancer in Motahari Breast Clinic, Shiraz,
Iran between 2004 and 2011. We estimated the rate of survival without recurrence
through the Kaplan-Meier method and the difference between the survival curves
was investigated using the log-rank test. Furthermore, Cox regression model was
used to model the effective factors in local recurrence as well as metastasis.
RESULTS: The mean age of the patients was 54.8 +/- 11.4 years. Estrogen receptor
positive, progesterone receptor positive, and human epidermal growth factor
receptor-2 positive were observed in 70.6%, 66.6%, and 34.4% of the cases,
respectively. The mean of the follow-up period was 3.7 +/- 1.8 years in all
patients. The results of the Kaplan-Meier method revealed 1-, 3-, 5-, and 7-year
rate of survival without recurrence as 96.4%, 78.4%, 66.3%, and 54.8%,
respectively. There was a significant relationship between survival without
recurrence and histology grade (hazard ratio [HR] = 1.66, P = 0.009), neural
invasion (HR = 1.74, P = 0.006), and progesterone receptors (HR = 0.69, P =
0.031). CONCLUSION: In this study, the rate of survival without recurrence in
breast cancer was 54.8%. Among factors, histology grade and neural involvement at
the time of diagnosis increased the chance of recurrence and progesterone
receptors caused a longer interval between diagnosis and recurrence.
PMID- 28503498
TI - Evaluation of Energy Balance on Human Telomerase Reverse Transcriptase (hTERT)
Alternative Splicing by Semi-quantitative RT-PCR in Human Umbilical Vein
Endothelial Cells.
AB - BACKGROUND: Decreased high-energy phosphate level is involved in endothelial cell
injury and dysfunction. Reduced telomerase activity in endothelial cells in
parallel with reduced energy levels might be due to altered direction of
alternative splicing machine as a complication of depleted energy during the
process of atherosclerosis. MATERIALS AND METHODS: Isolated human umbilical vein
endothelial cells (HUVECs) were treated for 24 hours by oligomycine (OM) and 2
deoxy glucose (2-DG). After 24 hours, the effect of energy depletion on
telomerase splicing pattern was evaluated using RT-PCR. Indeed, in both treated
and untargeted cells, nitric oxide (NO) and von Willebrand factor (vWF) were
measured. RESULTS: ATP was depleted in treated cells by 43.9% compared with
control group. We observed a slight decrease in NO levels (P = 0.09) and vWF (P =
0.395) in the setting of 49.36% ATP depletion. In both groups, no telomerase gene
expression was seen. Telomerase and housekeeping gene expression were found in
positive control group (colon cancer tissue) and sample tissue. CONCLUSIONS: The
absence of telomerase gene expression in HUVECs might be due to the mortality of
these cells or the low level of telomerase gene expression in these cells under
normal circumstances.
PMID- 28503499
TI - The Prevalence of Osmophobia in Migranous and Episodic Tension Type Headaches.
AB - BACKGROUND: Migraines are a neurological disease, of which the most common
symptom is an intense and disabling episodic headache. Many persons experience
sensory hyper excitability manifested by photophobia, phonophobia and osmophobia.
This study was planned to investigate the prevalence of osmophobia in migranous
and episodic tension type headache (ETTH). MATERIALS AND METHODS: A semi
structured questionnaire was administered to all patients to evaluate the
eventual presence of osmophobia during a headache attack and different
characteristics of osmophobia were determined. RESULTS: Osmophobia reported in
84% with migranous headache with aura, 74% of migranous patients without aura and
in 43.3% of those with ETTH. In 50% of patients, osmophobia was present in all of
their headache attacks, 11.7% had osmophobia in more than half of their attacks
(from 10 attacks they reported osmophobia in 5-9 ones) and others had this sign
in less than half of their attacks (from 10 attacks they reported osmophobia in
less than 5 ones). Most frequently the offending odors were scents (88%), foods
(54.2%) and cigarette smoke (62.5%). Osmophobia starts 30 min before the headache
starts in 22.7% of patients. CONCLUSION: Osmophobia appears structurally
integrated into the migraine history of the patient; however, for differential
diagnosis with ETTH, other criteria are necessary.
PMID- 28503500
TI - The Correlation between Different Risk Factors of Hepatitis C and Different
Genotypes.
AB - BACKGROUND: Hepatitis C infection is one of the health problems in the world.
Several known risk factors are responsible in transmission of this infection. We
are going to study the prevalence of these risk factors for different genotypes
of hepatitis C and if possible, specify probable relations between each risk
factor and transmission of each genotype. MATERIALS AND METHODS: This is a cross
sectional study done on 270 people who had positive anti-hepatitis C virus (HCV)
antibody and HCV RNA. Demographic specificity and possible risk factors were
collected using a questionnaire, and statistical analysis was done by SPSS
software (version 20). Chi-square test used to estimate the prevalence and
relation between each qualitative risk factor and HCV genotype transmitted.
Analysis of variance was used for studying the prevalence and relation between
quantitative risk factors and HCV genotypes. RESULTS: The sample size was 270
persons. Of these, 217 (80.4%) were men and 185 (68.5%) were infected with
genotype Type III. Most people were in age range of 31-40 years old 92 (34%).
Single people were 126 (46.7%) and 169 (62.6%) were high school and university
graduated. Tattooing as a risk factor had a meaningful relation with hepatitis C
genotype (P < 0.001). CONCLUSIONS: According to the findings, most people in
central provinces of Iran with hepatitis C are carrying genotype III, with most
prevalent risk factors such as intravenous drug use and unsafe sexual activity.
Besides, tattooing had a significant association with hepatitis C genotype, so
that in these groups of people, genotype I was more frequent isolated virus.
PMID- 28503501
TI - Acute Subdural Hematoma and Subarachnoid Hemorrhage Caused by Ruptured Cortical
Artery Aneurysm: Case Report and Review of Literature.
AB - The present report describes an acute subdural hematoma (ASDH) associated with
subarachnoid hemorrhage (SAH), due to ruptured cortical aneurysm. To our
knowledge, extremely rare cases of this sort have been reported so far. A 23-year
old male patient without previous trauma presented with severe headache and
rapidly decreasing level of consciousness to decerebrate status. Computed
tomography (CT) scan has demonstrated an ASDH together with SAH. Hematoma has
immediately been evacuated without any evaluation by angiography. After
evacuation of the thick subdural clot, a 10-mm aneurysm was revealed on a
precentral artery of frontal cortex, which was ligated. However, after 35 days
the patient discharged with left side hemiparesis and dysphasia, and just after
several months of admission he got symptom free. Ruptured cortical aneurysm
should be considered as one of the causes of spontaneous ASDH. Vascular anomaly
investigations are suggested for these cases, thus CT angiography or digital
subtraction angiography has to be considered if clinical condition allows.
PMID- 28503502
TI - Prevalence of Nonalcoholic Fatty Liver Disease and its Related Metabolic Risk
Factors in Isfahan, Iran.
AB - BACKGROUND: This study aimed to determine the prevalence of nonalcoholic fatty
liver disease (NAFLD) and its related risk factors among the general population
of Isfahan city located in the central part of Iran. MATERIALS AND METHODS: In
this cross-sectional study, the prevalence of NAFLD among 483 general adult
populations was determined using ultrasonography. Anthropometric and biochemical
variables were compared in groups with and without NAFLD and their predictive
value for occurrence of NAFLD was investigated also. RESULTS: Prevalence of NAFLD
was 39.3%. Frequency of focal fatty infiltration (FFI), Grade I, Grade II, and
Grade III of NAFLD was 9.5%, 21.1%, 7.2%, 1.4%, respectively. Prevalence of
different types of NAFLD and FFI, was not different between female and male
participants (P = 0.238). Ordinal regression was determined that all of the
studied variables have significant predictive value for NAFLD (P < 0.001, gamma =
0.615). Spearman correlation indicated that there was a significant relationship
between NAFLD and BMI (r = 0.37, P < 0.001), age (r = 0.15, P = 0.001), FBS (r =
0.20, P < 0.001), cholesterol (r = 0.19, P < 0.001), triglyceride (r = 0.20, P <
0.001), LDL (r = 0.16, P < 0.001), AST (r = 0.17, P < 0.001), and ALT (r = 0.31,
P < 0.001). CONCLUSIONS: Considering the high prevalence of NAFLD specially its
lower grades among Isfahani adult general population and their association with
studied variables, it seems that interventional studies which target-related
mentioned risk factors could reduce the overall occurrence of NAFLD.
PMID- 28503503
TI - Measurement Methods for Physical Activity and Energy Expenditure: a Review.
AB - Physical activity is defined as any bodily movement produced by skeletal muscles
that results in energy expenditure. The benefits of physical activity for health
maintenance have been well documented, especially in the prevention and
management of chronic diseases. Therefore, accurate measurement of physical
activity and energy expenditure is essential both for epidemiological studies and
in the clinical context. Given the large number of available methods, it is
important to have an understanding of each, especially when one needs to choose a
technique to use. The purpose of this review was to discuss the components of
total energy expenditure and present advantage and limitations of different
methods of physical activity and energy expenditure assessment.
PMID- 28503504
TI - Antioxidant Status and Risk of Gestational Diabetes Mellitus: a Case-Control
Study.
AB - Gestational diabetes mellitus (GDM) is described as glucose intolerance diagnosed
during pregnancy. Increased oxidative stress has implicated in diabetic problems.
The aim of the current study was to compare antioxidant capacity and antioxidant
nutrient intake between women with GDM (n = 40) and healthy pregnant women (n =
40). Demographic and obstetrics data were completed using interview technique and
dietary intakes by using a semi-quantitative food frequency questionnaire (FFQ)
with 168 items. The total antioxidant capacity (TAC) of serum was assessed by
double-antibody sandwich enzyme-linked immune-sorbent assay (ELISA) method.
Multivariate logistic regression was performed to compare independent variables
and other potential risk factors between 2 groups. The results showed that TAC
concentration of serum in women with GDM was significantly lower than in healthy
pregnant women (2.3 +/- 0.7 vs. 3.7 +/- 0.1 umol/L, p < 0.001). Intakes of
vitamin E (11.8 + 3.1 vs. 16.2 + 3.1 mg, p < 0.001), selenium (81 +/- 26 vs. 95
+/- 36 ug, p < 0.05) and zinc (7.4 +/- 1.9 vs. 9.1 +/- 1.7 mg, p < 0.001) were
significantly lower in women with GDM as compared to healthy pregnant women. In
contrast, the groups showed no significant difference in vitamin C, beta
carotene, selenium, fruit, and vegetable intake. Our findings showed that
antioxidant capacity is lower in women with GDM, possibly related to lower
intakes of vitamin E and zinc.
PMID- 28503505
TI - Depression Is a Mediator for the Relationship between Physical Symptom and
Psychological Well-being in Obese People.
AB - This present study aimed to investigate the association effect of obesity status,
physical symptom, insecure attachment, and depression on psychological well-being
in non-diabetic healthy Koreans. Height, weight, waist circumference, blood
pressure, and socio-psychological questionnaires (insecure attachment,
depression, and physical symptom psychological well-being, etc.) were examined in
123 healthy Koreans. Student t-test, correlation analysis, and mediation analysis
were performed. Study subjects were divided into 2 groups based on body mass
index (BMI, kg/m2): obesity (BMI >= 25, n = 36) and non-obesity (BMI < 25, n =
87). Obese people were older and showed higher proportion of males than non-obese
ones. Regarding the values of socio-psychological test, obesity group showed
lower insecure attachment, and higher physical symptom than non-obesity group. In
correlation and mediation analyses, depression was positively related to insecure
attachment and physical symptom in both BMI groups. Positive relationship between
physical symptom and insecure attachment was observed only in non-obesity group,
but not in obesity group. The effect of insecure attachment on psychological well
being was completely mediated by depression in both BMI groups. On the other
hand, the effect of physical symptom on psychological well-being was completely
mediated by depression in obesity group, but not in non-obesity group. In
conclusion, this study presented that the effects of physical symptom and
insecure attachment on psychological well-being were completely mediated by
depression in obese healthy Koreans, but not in non-obese ones. It will provide
useful data for extending the knowledge on the relationship between the physical
health and mental health.
PMID- 28503506
TI - Applicability Evaluation of Job Standards for Diabetes Nutritional Management by
Clinical Dietitian.
AB - This study was conducted to evaluate applicability of job standards for diabetes
nutrition management by hospital clinical dietitians. In order to promote the
clinical nutrition services, it is necessary to present job standards of clinical
dietitian and to actively apply these standardized tasks to the medical
institution sites. The job standard of clinical dietitians for diabetic nutrition
management was distributed to hospitals over 300 beds. Questionnaire was
collected from 96 clinical dietitians of 40 tertiary hospitals, 47 general
hospitals, and 9 hospitals. Based on each 5-point scale, the importance of
overall duty was 4.4 +/- 0.5, performance was 3.6 +/- 0.8, and difficulty was 3.1
+/- 0.7. 'Nutrition intervention' was 4.5 +/- 0.5 for task importance, 'nutrition
assessment' was 4.0 +/- 0.7 for performance, and 'nutrition diagnosis' was 3.4 +/
0.9 for difficulty. These 3 items were high in each category. Based on the grid
diagram, the tasks of both high importance and high performance were 'checking
basic information,' 'checking medical history and therapy plan,' 'decision of
nutritional needs,' 'supply of foods and nutrients,' and 'education of nutrition
and self-management.' The tasks with high importance but low performance were
'derivation of nutrition diagnosis,' 'planning of nutrition intervention,'
'monitoring of nutrition intervention process.' The tasks of both high importance
and high difficulty were 'derivation of nutrition diagnosis,' 'planning of
nutrition intervention,' 'supply of foods and nutrients,' 'education of nutrition
and self-management,' and 'monitoring of nutrition intervention process.' The
tasks of both high performance and high difficulty were 'documentation of
nutrition assessment,' 'supply of foods and nutrients,' and 'education of
nutrition and self-management.'
PMID- 28503507
TI - Nutritional Status of Korean Children and Adolescents with Attention Deficit
Hyperactivity Disorder (ADHD).
AB - Attention deficit hyperactivity disorder (ADHD) has been associated with an
elevated risk for obesity but this seems to be paradoxical to the fact that many
youths with ADHD have symptoms of hyperactivity. People diagnosed with ADHD tend
to have a high risk of developing undesirable diet habits and consequently have
health related problems. However, less attention has been paid to obesity in ADHD
while many efforts have been devoted to the prevention of childhood obesity in
mentally normal people. Hence the purpose of this study was to explore the
nutritional status and life habits of children and adolescents with ADHD (n = 76)
based on degree of obesity by utilizing the Korean National Health and Nutrition
Examination Survey (KNHANES) data from 2005-2013. As results the levels of blood
pressure, total triglycerides and the fat intake relative to total energy intake
in overweight ADHD group were higher than those in normal weight group.
Interestingly, overweight ADHD subjects consumed significantly less amount of
iron compared to normal weight ADHD subjects and the level of serum ferritin was
lower in the overweight ADHD group (59.0 ng/mL) than in the normal weight ADHD
group (47.9 ng/mL). After adjusting total energy intake, total vegetable
consumption was 14.3% lower in overweight group compared to the consumption in
normal weight group. These results indicate a plausible relationship of iron
status and obesity in ADHD subjects but this relationship may not be specific to
ADHD. A future study with case-control design is necessary to investigate the
association of obesity, nutrient intake, and cognitive/mental status of ADHD.
PMID- 28503509
TI - Nicotinamide Reduces Amyloid Precursor Protein and Presenilin 1 in Brain Tissues
of Amyloid Beta-Tail Vein Injected Mice.
AB - The purpose of this study is to investigate whether nicotinic acid (NA) and
nicotinamide (NAM) reduce the Alzheimer disease (AD)-related gene expression in
brain tissues of amyloid beta (Abeta)-injected mice. Male Crj:CD1 (ICR) mice were
divided into 6 treatment groups; 1) control, 2) Abeta control, 3) Abeta + NA 20
mg/kg/day (NA20), 4) Abeta + NA40, 5) Abeta + NAM 200 mg/kg/day (NAM200), and 6)
Abeta + NAM400. After 1-week acclimation period, the mice orally received NA or
NAM once a day for a total of 7 successive days. On day 7, biotinylated Abeta42
was injected into mouse tail vein. At 5 hours after the injection, blood and
tissues were collected. Abeta42 injection was confirmed by Western blot analysis
of Abeta42 protein in brain tissue. NAM400 pre-treatment significantly reduced
the gene expression of amyloid precursor protein and presenilin 1 in brain
tissues. And, NAM200 and NAM400 pre-treatments significantly increased sirtuin 1
expression in brain tissues, which is accompanied by the decreased brain
expression of nuclear factor kappa B by 2 doses of NAM. Increased expression of
AD-related genes was attenuated by the NAM treatment, which suggests that NAM
supplementation may be a potential preventive strategy against AD-related
deleterious changes.
PMID- 28503508
TI - Carbohydrate Composition Associated with the 2-Year Incidence of Metabolic
Syndrome in Korean Adults.
AB - The aim of this study was to investigate the association between macronutrient
composition and metabolic syndrome (MetS) incidence in Korean adults. Data were
obtained from a cohort of 10,030 members aged 40 to 69 years who were enrolled
from the 2 cities (Ansung and Ansan) between 2001 and 2002 to participate in the
Korean Genome Epidemiology Study. Of these members, 5,565 participants, who were
free of MetS and reported no diagnosis of cardiovascular disease at baseline,
were included in this study. MetS was defined using the criteria of the National
Cholesterol Education Program-Adult Treatment Panel III and Asia-Pacific criteria
for waist circumference. MetS incidence rate were identified during a 2-year
follow-up period. Baseline dietary information was obtained using a semi
quantitative food frequency questionnaire. Multivariate logistic regression
analysis was used to evaluate the association between the quartiles of
percentages of total calorie from macronutrients consumed and MetS incidence. In
analyses, baseline information, including age, sex, body mass index, income
status, educational status, smoking status, alcohol drinking status, and physical
activity level was considered as confounding variables. Participants with the
second quartile of the percentages of carbohydrate calorie (67%-70%) had a 23%
reduced odds ratio (95% confidence interval, 0.61-0.97) for MetS incidence
compared with those with the fourth quartile after adjusting for confounding
variables. The findings suggest that middle aged or elderly Korean adults who
consume approximately 67%-70% of calorie from carbohydrate have a reduced risk of
MetS.
PMID- 28503511
TI - Erratum: Dietary Antioxidant Capacity and Its Association with Preeclampsia.
AB - [This corrects the article on p. 47 in vol. 6, PMID: 28168181.].
PMID- 28503510
TI - A Case Report of the Nutrition Support for a Patient with HELLP Syndrome.
AB - A 30-year-old female patient, 18 weeks gestational age, with no prior medical
history was admitted to hospital complaining severe right upper quadrant pain.
The patient was admitted to intensive care unit (ICU) after emergency surgery to
treat intraperitoneal hemorrhage caused by rupture of liver hematoma. Despite the
absence of high blood pressure, the patient was diagnosed with hemolysis,
elevated liver enzymes, and low platelet count (HELLP) syndrome on the basis of
abnormal levels of blood aspartate aminotransferase/alanine aminotransferase,
lactate dehydrogenase, total bilirubin, direct bilirubin, C-reactive protein
(CRP) and platelet along with liver damage and proteinuria. While in ICU, the
patient was given total parenteral nutrition (TPN) and enteral nutrition (EN) for
-20 days because oral feeding was impractical. In the early stage, TPN supply was
not sufficient to meet the elevated nutritional demand induced by disease and
surgery. Nevertheless, continuous care of nutrition support team enabled
satisfactory EN and, subsequently, oral feeding which led to improvement in
patient outcome.
PMID- 28503512
TI - Analysis of Nested Case-Control Study Designs: Revisiting the Inverse Probability
Weighting Method.
AB - In nested case-control studies, the most common way to make inference under a
proportional hazards model is the conditional logistic approach of Thomas (1977).
Inclusion probability methods are more efficient than the conditional logistic
approach of Thomas; however, the epidemiology research community has not accepted
the methods as a replacement of the Thomas' method. This paper promotes the
inverse probability weighting method originally proposed by Samuelsen (1997) in
combination with an approximate jackknife standard error that can be easily
computed using existing software. Simulation studies demonstrate that this
approach yields valid type 1 errors and greater powers than the conditional
logistic approach in nested case-control designs across various sample sizes and
magnitudes of the hazard ratios. A generalization of the method is also made to
incorporate additional matching and the stratified Cox model. The proposed method
is illustrated with data from a cohort of children with Wilm's tumor to study the
association between histological signatures and relapses.
PMID- 28503513
TI - Transanal Minimally Invasive Surgery After Chemoradiotherapy: Widening Scope of
Indications for Local Excision.
PMID- 28503514
TI - Mucinous Subtype in Patients With Colorectal Cancer.
PMID- 28503515
TI - Synthetic Versus Biological Mesh-Related Erosion After Laparoscopic Ventral Mesh
Rectopexy: A Systematic Review.
AB - PURPOSE: This review reports the incidence of mesh-related erosion after ventral
mesh rectopexy to determine whether any difference exists in the erosion rate
between synthetic and biological mesh. METHODS: A systematic search of the
MEDLINE and the Ovid databases was conducted to identify suitable articles
published between 2004 and 2015. The search strategy capture terms were
laparoscopic ventral mesh rectopexy, laparoscopic anterior rectopexy, robotic
ventral rectopexy, and robotic anterior rectopexy. RESULTS: Eight studies (3,956
patients) were included in this review. Of those patients, 3,517 patients
underwent laparoscopic ventral rectopexy (LVR) using synthetic mesh and 439 using
biological mesh. Sixty-six erosions were observed with synthetic mesh (26 rectal,
32 vaginal, 8 recto-vaginal fistulae) and one (perineal erosion) with biological
mesh. The synthetic and the biological mesh-related erosion rates were 1.87% and
0.22%, respectively. The time between rectopexy and diagnosis of mesh erosion
ranged from 1.7 to 124 months. No mesh-related mortalities were reported.
CONCLUSION: The incidence of mesh-related erosion after LVR is low and is more
common after the placement of synthetic mesh. The use of biological mesh for LVR
seems to be a safer option; however, large, multicenter, randomized, control
trials with long follow-ups are required if a definitive answer is to be
obtained.
PMID- 28503516
TI - Transanal Minimally-Invasive Surgery for Treating Patients With Regressed Rectal
Cancer After Preoperative Chemoradiotherapy.
AB - PURPOSE: Although the standard treatment for patients with locally advanced
rectal cancer managed by preoperative chemoradiotherapy (CRT) is a radical
resection, local excisions are used in highly-selective cases. Recently,
transanal minimally-invasive surgery (TAMIS) has emerged as a feasible technique
for local excision of midrectal lesions. We assess the feasibility of using TAMIS
to treat patients with locally advanced rectal cancer who showed good response to
CRT. METHODS: From October 2010 to June 2013, 35 consecutive patients with rectal
cancer managed by using preoperative CRT underwent TAMIS. After a single-incision
laparoscopic surgery port had been introduced into the anal canal, a full
thickness local excision with conventional laparoscopic instruments was
performed. We retrospectively reviewed a prospectively collected database of
these cases. RESULTS: Of the 35 patients analyzed, 18 showed pathologic complete
responses and 17 had residual lesions (2 ypTis, 4 ypT1, 9 ypT2, and 2 ypT3); 34
(97.1%) showed clear deep, lateral margins. The median distance of lesions from
the anal verge was 5 cm. All procedures were completed laparoscopically, and the
median operating time was 84 minutes. No intraoperative events or morbidities
were seen in any of the patients, except one with wound dehiscence, who was
treated conservatively. The median postoperative hospital stay and follow-up
period were 4 days and 36 months, respectively. During the study period, no
patients died, but 5 (14.3%) experienced recurrence, including one recurrence at
the TAMIS site. CONCLUSION: TAMIS seems to be a feasible, safe modality for
treating patients with locally advanced rectal cancer who show good response to
preoperative CRT.
PMID- 28503517
TI - Prognostic Significance of Mucinous Histologic Subtype on Oncologic Outcomes in
Patients With Colorectal Cancer.
AB - PURPOSE: Mucinous adenocarcinomas account for about 10% of all colorectal
cancers. This study aimed to investigate the prognostic impact of mucinous
histologic subtype on oncologic outcomes in patients with colorectal cancer.
METHODS: This retrospective study was performed at two large tertiary university
hospitals. We analyzed the characteristics, prognostic factors, and survival of
patients with colorectal cancer who were treated and followed up between 2000 and
2013. RESULTS: Totally, 144 of 1,268 patients with a colorectal adenocarcinoma
(11.4%) had mucinous histologic subtype. Statistically significant results found
in this research are as follows: Mucinous histologic subtype tended to present in
younger patients and to have larger tumor size, higher histologic grade, higher
node stage, larger number of positive nodes, and higher rate of perineural
invasion compared to nonmucinous histologic subtype. On the univariate analysis,
mucinous subtype was a prognostic factor for disease-free and overall survival.
On the multivariate analysis, primary tumor location, node stage and lymphatic
vascular invasion were independent prognostic factors for the local control rate.
Rectal tumor location, higher disease stage, tumor grade II, and presence of
lymphatic-vascular invasion had negative influences on disease-free survival, as
did rectal tumor location, higher disease stage and presence of lymphatic
vascular invasion on overall survival. CONCLUSION: Mucinous histologic subtype
was associated with some adverse pathologic features in patients with colorectal
cancer; however, it was not an independent prognostic factor for oncologic
outcome.
PMID- 28503518
TI - Laparoscopic Vaginal Suspension and Rectopexy for Rectal Prolapse.
AB - PURPOSE: Laparoscopic procedures for the treatment of patients with a rectal
prolapse have gained increasing worldwide acceptance because they have lower
recurrence and better functional outcome than perineal procedures. Nevertheless,
ideal surgical methods are still not available. We propose a new surgical
technique, laparoscopic vaginal suspension and rectopexy, for correcting a full
thickness rectal prolapse and/or middle-compartment prolapse. This study assessed
the short-term outcomes for patients who underwent laparoscopic vaginal
suspension and rectopexy. METHODS: Between April 2014 and April 2016, 69 female
patients underwent laparoscopic vaginal suspension and rectopexy to correct a
rectal prolapse. Demographics, medical histories, and surgical and follow-up
details were collected from their medical records. In addition to the clinical
outcome, we repeated defecation proctography and a questionnaire regarding
functional results three months after surgery. RESULTS: No major morbidities or
no mortalities occurred. The defecation proctography confirmed excellent
anatomical result in all cases. Of 7 patients with combined middle-compartment
prolapses, we observed good anatomical correction. During follow-up, full
thickness recurrence occurred in one patient. Preoperative fecal incontinence was
improved significantly at 3 months (mean Wexner score: 12.35 vs. 7.71; mean FISI:
33.29 vs. 21.07; P < 0.001). Analysis of responses to the fecal incontinence
quality of life (FIQOL) questionnaire showed overall improvement at 3 months
compared to the preoperative baseline (mean pre- and postoperative FIQOL scores:
12.11 vs. 14.39; P < 0.004). CONCLUSION: Laparoscopic vaginal suspension and
rectopexy is a new combined procedure for the treatment of patients with rectal
prolapses. It has excellent functional outcomes and minimal morbidity and can
correct and prevent middlecompartment prolapses.
PMID- 28503521
TI - Can exercise rehabilitation evolve into a new therapeutic area?
PMID- 28503520
TI - Pulmonary Sarcoidosis That Developed During the Treatment of a Patient With Crohn
Disease by Using Infliximab.
AB - For inflammatory bowel disease (IBD), antitumor necrosis factor treatment offers
a new direction for both patients and medical doctors. This treatment has
dramatically improved the quality of life for patients with ulcerative colitis
and Crohn disease (CD). However, with increasing usage and longer follow-up
periods, a wider range of possible adverse effects may be encountered. We report
an unusual case of pulmonary sarcoidosis developed during the treatment of a
patient with CD by using infliximab. A 30-year-old male who had been treated for
CD with infliximab for 18 months was admitted due to abnormal opacities on chest
radiography. Chest computed tomography displayed clustered small nodules in both
lobes and enlarged multiple lymph nodes. The patient was diagnosed with
sarcoidosis from the results of a biopsy of the subcarinal lymph node. Lung
lesions were improved five months after infliximab was stopped.
PMID- 28503519
TI - Multiple Myeloma Mimics Bone Metastasis From a Rectal Adenocarcinoma.
AB - A presumptive diagnosis of bone metastasis can be easily made when a patient with
a history of colorectal cancer develops bone lesions that are seen on follow-up
imaging. In this case report, we describe a patient whose multiple bone lesions
were wrongly attributed to a recurrence of rectal cancer rather than being
identified as multiple myeloma lesions. When clinicians detect new, abnormal,
bony lesions in a patient with a previous history of cancer, they should consider
diseases such as multiple myeloma in their differential diagnosis.
PMID- 28503522
TI - Treadmill exercise alleviates depressive symptoms in rotenone-induced Parkinson
disease rats.
AB - Parkinson disease (PD) is characterized by selective loss of the dopaminergic
neurons. The symptoms of depression following PD are closely associated with
reduced activity of the serotonergic system in the dorsal raphe. We explored the
antidepressive effect of exercise and its possible mechanism using the rotenone
induced PD rats. PD rats were induced by subcutaneously injection with rotenone
for 14 days. The rats in the exercise groups were made to run on a treadmill for
30 min once a day during 14 consecutive days. Forced swimming test,
immunohistochemistry for serotonin (5-hydroxytryptamine, 5-HT), tryptophan
hydroxylase (TPH), and western blot for serotonin 1A (5-HT1A) receptor were
conducted. Injection of rotenone induced PD rats. PD rats showed depressive state
and treadmill exercise ameliorated this depressive state. 5-HT, TPH, and 5-HT1A
receptor expressions in the dorsal raphe were suppressed by rotenone injection
and treadmill exercise increased the expressions of 5-HT, TPH, and 5-HT1A
receptor in the rotenone-injected rats. The present results show that treadmill
exercise ameliorated depressive symptoms in the rotenone-induced PD rats. The
antidepressive effect of treadmill exercise might be ascribed to the enhancement
of serotonergic function through upregulation of 5-HT1A expression in the dorsal
raphe.
PMID- 28503523
TI - Treadmill exercise ameliorates depressive symptoms through increasing serotonin
expression in postpartum depression rats.
AB - Postpartum depression (PPD) is defined as the depressive symptoms that occur from
the moment of delivery until 12 months after delivery. PPD symptoms are closely
associated with reduced activity of the serotonergic system. Serotonin (5
hydroxytryptamine, 5-HT) plays an important role in the pathogenesis of
depression. Tryptophan hydroxylase (TPH) catalyzes the rate-limiting step of 5-HT
biosynthesis in the serotonergic neurons. Exercise exerts anti-depressive effect
on depression patients as well as on animal models of depression. In the present
study, the effect of treadmill exercise on PPD was investigated using rats. For
this study, open field test for activity and forced swimming test for depressive
symptoms, and immunohistochemistry for 5-HT and TPH were conducted. The rats in
the exercise groups were forced to run on a motorized treadmill for 30 min once a
day for 2 weeks. Activity in the open field test was decreased in the postpartum
rats, however, performing treadmill running increased activity in the postpartum
rats. The climbing time was decreased and the immobility time was increased in
the postpartum rats. Treadmill exercise increased climbing time and suppressed
immobility time in the postpartum rats. 5-HT and TPH expressions in the dorsal
raphe were suppressed in the postpartum rats, and treadmill exercise enhanced 5
HT and TPH expressions in the postpartum rats. Treadmill exercise ameliorated the
PPD very effectively by enhancing serotonin level.
PMID- 28503524
TI - Treadmill exercise improves motor and memory functions in cerebral palsy rats
through activation of PI3K-Akt pathway.
AB - Cerebral palsy (CP) is a chronic disorder characterized by physical disability
and disruption of brain function. We evaluated the effects of treadmill exercise
on motor and memory functions in relation with phosphatidylinositol 3-kinase
(PI3K)-Akt pathway using CP rat model. Rota-rod test, step-down avoidance task, 5
bromo-2'-deoxyuridine (BrdU) immunohistochemistry, and western blot for synapsin
I, postsynaptic density-95 (PSD-95), PI3K, Akt, and glycogen synthase kinase
3beta (GSK-3beta) were performed. CP was induced by maternal lipopolysaccharide
(LPS)-injection with sensorimotor restriction. Five weeks after birth, the rats
in the exercise groups were made to run on the treadmill for 30 min per one day,
5 times a week, during 4 weeks. Motor and memory functions were impaired in the
LPS-induced CP rats and tread-mill exercise increased motor and memory functions
in the CP rats. Cell proliferation in the hippocampus was suppressed in the LPS
induced CP rats and treadmill exercise increased hippocampal cell proliferation
in the CP rats. Expressions of synapsin I, PSD-95, phosphorylated (p)-PI3K, and p
Akt were decreased in the LPS-induced CP rats and treadmill exercise enhanced the
expressions of synapsin I, PSD-95, p-PI3K, and p-Akt in the CP rats. GSK-3beta
expression was increased in the LPS-induced CP rats and treadmill exercise
suppressed GSK-3beta expression in the CP rats. The present results suggest that
treadmill exercise might improve motor and memory functions through activation of
PI3K-Akt pathway.
PMID- 28503525
TI - Study on emotion by rest time in mice with repetitive sleep deprivation.
AB - Sleep deprivation (SD) inhibits normal biorhythms, causing physical and mental
problems. To solve the problems caused by SD, fundamental measures are needed. I
investigated change of recovery by rest time in psychological aspect after
repetitive SD. The mice were divided into four groups: control 24-hr rest after
24-hr SD group, 48-hr rest after 24-hr SD group, and 72-hr rest after 24-hr SD
group (n=20 in each group). I carried out SD in the water cage included multiple
platforms. Repetitive SD executes for 36 days. I measured weight every week after
SD for 6 weeks. To check emotional condition, I carried out intruder-evoked
aggression test and modified forced swimming test. In the present results, group
treated 24-hr rest and 48-hr rest after 24-hr SD showed lower natural
aggressiveness and high depression. However, group treated 72-hr rest after 24-hr
SD indicated emotional changes to recover the normal conditions. In the weight
change, all group showed significant decrease compared to control for 6 weeks. I
suggest that appropriate rest time after SD can help to restore emotional change.
PMID- 28503526
TI - Be seeded or not be seeded? A study with Olympic judo athletes.
AB - The main purpose of the present study was to calculate the probability-based on a
Bayesian approach-to win a medal in the Olympic Games given the athlete is seeded
and to verify if the number one ranked athlete has any advantage compared to
other seeded athletes concerning his/her chances to be Olympic champion. For
this, data from athletes who took part in the London 2012 and Rio 2016 Olympic
Games were considered. For males the probability of seeded athletes to win a
medal was 41.1% and 42.9%, while for females it was 35.7% and 44.6% at London
2012 and Rio 2016, respectively. Furthermore, the probability of athletes ranked
as number one to become Olympic champion among the seeded athletes was 19.5% and
36.8% for males and 32.3% and 36.8% for females in London 2012 and Rio 2016,
respectively. Based on these results the cost-benefit of investing human and
financial resources to qualify an athletes among the top eight competitors and
his/her exposure to competitions-resulting in technical-tactical analysis of the
opponent and higher risk of injury-should be carefully analyzed when determining
the competition calendar to each athlete.
PMID- 28503527
TI - Postactivation potentiation in elite young soccer players.
AB - The aim of this study was to investigate the acute effects of 16 different
combinations to cause the postactivation potentiation (PAP) in elite young soccer
players. Squat exercise in 4 different intensities (40%, 60%, 80%, and 100% one
repetition maximum [1RM]) was performed and its effects were evaluated in the
performance of countermovement jump (CMJ), after 4 different recovery times (1,
3, 5, and 10 min). For this purpose, 25 young soccer players, underwent five
experimental sessions. At the first session the control to determine 1RM in half
squat was carried out. The following four experimental sessions were comprised of
four intensity combinations with four different recovery intervals in order to
perform the CMJ test later, randomly determined and with 30-min interval between
each combination. The conditions were compared using an analysis of variance with
repeated measurements, followed by Bonferroni test, using 5% significance level
(P<0.05). The different intensities investigated did not provide significant
increases in CMJ height, but significant differences were noted in recovery time,
where, at CMJ maximum height, 1-min interval was better than after 3 min
(P<0.05), 5, and 10 min (P<0.001). On the average jump performances, 1-min
interval resulted in better results (P<0.001) compared to other intervals. The 10
min recovery resulted in poorer performances compared to the other intervals
(P<0.001). Our results indicate that regardless the intensity used in the half
squat exercise with elite young soccer players, the 1-min recovery time was more
appropriate to promote an increase in vertical jump.
PMID- 28503528
TI - The development of anger management program based on acceptance and commitment
therapy for youth taekwondo players.
AB - This study aimed to develop an intervention program based on acceptance and
commitment therapy (ACT) for youth taekwondo players. Eight sessions of the ACT
program were provided to nine youth taekwondo players. The content analysis was
conducted for the activities, activity sheets, assignments, and program
evaluations. First of all, the results showed that the ACT program changed the
participants' diverse psychological inflexibility a flexible and value-oriented
state, which was supported by their positive mood changes after each session.
Secondly, 'walking meditation,' 'a bus driver and a passenger role play,' and
'writing a letter to the self' were positively evaluated according to the
analysis on the feedbacks and evaluations on each session and activity. Lastly,
overall evaluation on the ACT program indicated that there were changes in a
positive attitude, thoughts, and feelings (anger and irritation) toward
taekwondo. The most memorable activities were 'eating meditation,' 'breath
counting meditation,' and 'welcoming the beggar' exercise. These results suggest
that an intervention program based on the ACT may have a positive impact on anger
management for youth.
PMID- 28503530
TI - Caffeine supplementation affects the immunometabolic response to concurrent
training.
AB - The aim of the present study was to investigate the effects of caffeine (CAF) and
carbohydrate (CHO) intake on strength performance and its metabolic and
inflammatory responses during concurrent training. Seven active males ingested a
double-placebo (P), CAF (capsule 5 mg/kg) or CHO (20% maltodextrin solution)
supplementation before strength exercise. Participants performed three randomized
sessions of 5,000-m high-intensity intermittent aerobic exercise at maximal
intensity followed by strength exercise, performing after the P, CHO, and CAF
intake. The blood samples were collected before (pre) and immediately after
concurrent strength exercise (post). We found a similar number of repetitions and
total volume in all supplementation groups. There was a main effect of time on
glucose, lactate, and interleukin (IL)-6 (P<0.05). When compared the changes
between groups (postvalues minus prevalues), there was lower glucose in CAF group
when compared to CHO group (CAF= 5.0+/-10.4 vs. CHO=27.8+/-20 vs. P=15.1+/-14,
P=0.031) and higher IL-6 levels (CAF=11.9+/-9.2 vs. CHO=-2.4+/-1.7 vs. P=4.3+/-
11.7, P=0.017). There was significant interaction for glucose and lactate
(P<0.001). In conclusion, CAF and CHO intake did not improve strength performance
during concurrent strength training in active males. However, CAF affected
immunometabolic responses.
PMID- 28503531
TI - Relationship between cardiopulmonary responses and isokinetic moments: the
optimal angular velocity for muscular endurance.
AB - Most protocols for testing and rehabilitation for recovery and improvement of
muscular endurance have been set at 180 degrees /sec, 240 degrees /sec, and 300
degrees /sec. These protocols can cause confusion to clinical providers or other
researchers. This study was aimed at investigating the optimal isokinetic angular
speed for measuring or developing muscular endurance after assessing the
relationship between cardiopulmonary responses and isokinetic moments. This study
was conducted with 31 male and female college students. Graded exercise test and
body composition were measured as well as the isokinetic moments of the knee
muscles at three angular speeds: 180 degrees /sec, 240 degrees /sec, and 300
degrees /sec. The specific isokinetic moments of knee muscles that were measured
included: peak torque (PT) and total work (TW) on extensor (e) and flexor (f) of
knee joints, which were denoted as ePT180, fPT180, eTW180, fTW180, ePT240,
fPT240, eTW240, fTW240, ePT300, fPT300, eTW300, and fTW300 according to the three
angular speeds. Spearman correlation test was used to examine the relationship
between the sum means of cardiopulmonary responses and the variables of
isokinetic moments. This study confirmed that the optimal angular speed for
testing or training for muscular endurance was 180 degrees /sec, which showed a
stronger relationship between cardiopulmonary responses and isokinetic moments.
Therefore, this angular speed is recommended for testing and training for
muscular endurance of the knee joints.
PMID- 28503529
TI - Regular physical education class enhances sociality and physical fitness while
reducing psychological problems in children of multicultural families.
AB - This study investigated the influence of physical education class (PEC) as an
intervention method for aggression, sociality, stress, and physical fitness
levels in children from multicultural families. The hypothesis was that
participating in PEC would result in reduced aggression and stress and improved
sociality and physical fitness in multicultural children. A three-item
questionnaire, a body composition test, and physical fitness tests were given
three times. Eighty-four subjects were divided into four groups: multicultural
children who participated in PEC (multi-PEG, n=12), multicultural children who
did not participate in PEC (multi-NPEG, n=13), single-cultural children who
participated in PEC (sing-PEG, n=11), and single-cultural children who did not
participate in PEC (sing-NPEG, n=12), respectively. Parametric and nonparametric
statistical methods were conducted on the collected data with a significance
level set a priori at P<0.05. After 8 weeks of PEC, fat mass (F=2.966, P=0.045)
and body mass index (F=3.654, P=0.021) had significantly different interaction
effects. In the aspect of interaction effects from physical fitness variables,
cardiopulmonary endurance (F=21.961, P=0.001), flexibility (F=8.892, P=0.001),
muscular endurance (F=31.996, P=0.001), muscular strength (F=4.570, P=0.008), and
power (F=24.479, P=0.001) were significantly improved in the multi-PEG compared
to those of the other three groups. Moreover, sociality (F=22.144, P=0.001) in
the multi-PEG was enhanced, whereas aggression (F=6.745, P=0.001) and stress
(F=3.242, P=0.033) levels were reduced. As conclusion, the PEC reduced aggression
and stress levels, and improved sociality and physical fitness levels after 8
weeks. This study confirmed that PEC for children from multicultural families can
improve psychosocial factors and physical health.
PMID- 28503532
TI - Changes in gait kinematics and muscle activity in stroke patients wearing various
arm slings.
AB - Stroke patients often use various arm slings, but the effects of different slings
on the joint kinematics and muscle activity of the arm in the gait have not been
investigated. The effects of joint kinematics and muscle activity in the gait
were investigated to provide suggestions for gait training for stroke patients.
In all, 10 chronic stroke patients were voluntarily recruited. An eight-camera
three-dimensional motion analysis system was used to measure joint kinematics
while walking; simultaneously, electromyography data were collected for the
anterior and posterior deltoids and latissimus dorsi. The amplitude of pelvic
rotation on the less-affected side differed significantly among the different arm
slings (P<0.05). Changes in the knee kinematics of the less-affected side also
differed significantly (P<0.05), while there were no significant differences in
the muscle activity of the affected arm. In stroke patients, an extended arm
sling is more useful than no sling or a flexed arm sling in terms of the
amplitude of the rotation of the less-affected pelvic side in the stance phase
while walking. The less-affected knee joint is flexed more without a sling than
with any sling. All arm slings support the extension of the contralateral knee.
PMID- 28503533
TI - Effect of core strengthening with pelvic proprioceptive neuromuscular
facilitation on trunk, balance, gait, and function in chronic stroke.
AB - The purpose of this study was to evaluate the effects of core strengthening
combined with pelvic proprioceptive neuromuscular facilitation (PNF) on trunk
impairment, balance, gait, and functional ability of chronic stroke patients.
Twenty-three participants with chronic stroke were recruited and randomly
allocated to one of the two groups: core strengthening combined with pelvic PNF
(group 1, n=13), and pelvic PNF with trunk flexibility exercises (group 2, n=10).
Intervention was given to both groups for 60 min per session 5 times per week for
4 weeks. Performance of both groups was evaluated on Trunk Impairment Scale,
Tinetti Performance Oriented Mobility Assessment (Tinetti-POMA), Balance
Evaluation Systems Test (Mini-BESTest), Wisconsin Gait Scale, and Barthel
Activities of Daily Living Index prior to and after the completion of the
intervention. The comparison between postintervention scores of Tinetti-POMA
between group 1 (18.76+/-1.78) and group 2 (16.8+/-1.87) and Mini-BESTest group 1
(16.15+/-1.28) and group 2 (14.7+/-1.41) showed significant difference (P=0.018).
The results indicated that core stabilisation combined with pelvic PNF was more
effective for improving trunk impairment, balance and gait of chronic stroke
patients.
PMID- 28503535
TI - Validity and reliability evidence of the physical activity level screening for
preschoolers with developmental delays and/or disabilities.
AB - Psychometric properties of the physical activity level screening (PALS) for
preschoolers with a developmental delay and/or a disability were examined in this
study. The mean age of participants (16 boys and 14 girls) was 54.9 months
(standard deviation, 10.4). Each participant wore one Actical accelerometer and
was filmed for 20 min during the active play time. Intrarater and interrater
reliability, and validity of the PALS data were examined. The proportion of
agreement for intrarater was 87.5% and 85.6% for interrater reliability.
Intraclass correlation coefficients were 0.99 for intrarater and 0.96 for
interrater. The PALS data showed moderate correlation with Actical data (r=0.67,
P<0.01).
PMID- 28503534
TI - Effects of three spinal stabilization techniques on activation and thickness of
abdominal muscle.
AB - In this study, we examine the thickness of the abdominal muscle and its activity
during the performance of the three drawing-in methods. The subjects were 20
healthy male and female students in their 20s. Using ultrasonography and
electromyography, the experimenter measured the thickness of the transversus
abdominis (TrA) muscle, internal oblique (IO) muscle and external oblique (EO)
muscle. The ultrasonography measurements for the drawing-in manoeuver (DI),
abdominal bracing, and posterior pelvic tilt (PT) techniques were 0.64+/-0.20,
0.54+/-0.15, and 0.46+/-0.12, respectively, with significant differences for the
TrA. The electromyography results of the DI, SA, and PT techniques were 4.35+/
1.72, 3.00+/-1.48, and 2.70+/-1.52, respectively, for the IO. There was a
significant difference in the DI, SA, and PT techniques for the EO (5.10+/-3.30,
3.85+/-3.89, 2.25+/-1.29, respectively). The DI method activated the oblique
abdominal muscles, but there was no great change in their thickness; the TrA,
however, was selectively strengthened through changes in its thickness.
PMID- 28503536
TI - Exercise tolerance improves after pulmonary rehabilitation in pulmonary
hypertension patients.
AB - Pulmonary rehabilitation (PR) is part of the recommended management plan of
pulmonary hypertension (PHTN) and is important to better quality of life and
exercise tolerance. This study aimed at determining effectiveness of PR on
exercise capacity. Retrospective chart analysis was conducted on patients
referred to our PHTN clinic for PR. Patients who had PHTN diagnosed on right
heart catheterization (defined by mean pulmonary artery pressure>25 mmHg) and
completed a standardized 12-week PR program were considered for the study.
Patients' baseline exercise tolerance was recorded as speed attainable on a
treadmill and duration of exercise in minutes. Demographics, age, sex, and oxygen
use were obtained from chart review. Eighteen PHTN patients (5 male, 13 female;
mean age 67.7+/-11.6 years) were considered for the study (six World Health
Organization [WHO] group 1 pulmonary arterial hypertension [33.33%], eight WHO
group III PHTH [44.44%], two WHO group IV and two WHO V PHTN [11.11%]). Treadmill
speed improved following rehabilitation (1.3 mph [interquartile range {IQR}, 1.0
1.8 mph] to 2.2 mph [IQR, 1.3-2.8 mph]; P<0.0001, Wilcoxon signed rank test).
Median exercise time improved (27 min (IQR, 22-30 min) to 30 min (IQR, 24-30
min); not significant. Improvement was defined only as an increase in speed or
duration, or both. Sixteem of 18 participants improved (88.9% [95% exact binomial
confidence interval, 65.3%-98.6%). Patients with PHTN benefit from a structured
PR program to improve their exercise capacity and should be enrolled in PR
programs as part of their management.
PMID- 28503537
TI - Effects of inspiratory muscle exercise in the pulmonary function, autonomic
modulation, and hemodynamic variables in older women with metabolic syndrome.
AB - The aim of the present study was to investigate the effects of inspiratory muscle
exercise (IME) on metabolic and hemodynamic parameters, cardiac autonomic
modulation and respiratory function of older women with metabolic syndrome (MS).
For this, sixteen older women with MS and 12 aged-matched controls participated
of the present study. Two days before and 2 days after the main experiment,
fasting blood samples (i.e., total cholesterol, triglycerides and blood glucose),
cardiac autonomic modulation (i.e., heart rate variability), and respiratory
muscle function were obtained and evaluated. The sessions of physical exercise
was based on a IME, which was performed during 7 days. Each session of IME was
performed during 20 min, at 30% of maximal static inspiratory pressure. In the
results, MS group presented higher levels of triglycerides, blood glucose, and
systolic blood pressure when compared to control group. IME was not able to
change these variables. However, although MS group showed impaired respiratory
muscle strength and function, as well as cardiac autonomic modulation, IME was
able to improve these parameters. Thus, the data showed that seven days of IME
are capable to improve respiratory function and cardiac autonomic modulation of
older women with MS. These results indicate that IME can be a profitable therapy
to counteracting the clinical markers of MS, once repeated sessions of acute IME
can cause chronical alterations on respiratory function and cardiac autonomic
modulation.
PMID- 28503538
TI - Effects of a static stretch using a load on low back pain patients with shortened
tensor fascia lata.
AB - Stretch of tensor fascia lata (TFL) improves range of motion on hip and pelvis
and it reported to help reduce low back pain. Accordingly, the purpose of this
study was to investigate effects of static stretching using a load on TFL in
patients with low back pain. Twenty three subjects were recruited according to
the selection criteria. The subjects were randomly assigned to static stretching
group (control, n=12), and a static stretching using a load group (experimental,
n=11). All group performed stretching for 15 min (side for 50 sec per time and a
rest for 30 sec) per day in the left side and the right, respectively, for 2
weeks. Before and after the intervention, all groups measured visual analogue
scale (VAS), stand and reach test, and the Oswestry disability index (ODI). In
the present results, we found that the experimental group showed significant
differences in VAS, stand and reach test, and the ODI (P<0.05) in before and
after the intervention. Therefore, static stretching using a load can be actively
utilized for low back pain patients with shortened TFL.
PMID- 28503539
TI - Differences in Pes Planus and Pes Cavus subtalar eversion/inversion before and
after prolonged running, using a two-dimensional digital analysis.
AB - In sports, there is a constant discussion about the hyper-pronation and
supination of the foot during loading and its relation to injuries or discomfort.
The purpose of the present study was to investigate the possible differences in
the subtalar joint in the midstance phase of running, between individuals with
Pes Planus and Pes Cavus, after 5 min and 45 min of running. Thirty-four
subjects, meeting the requirements for Pes Planus (30 feet) and Pes Cavus (35
feet), according to the criteria for Medial Longitudinal Arch-angle, were
included in the study. The calcaneal vertical angle, representing the
eversion/inversion of the subtalar joint, was measured using with two-dimensional
digital analysis and Dartfish Software with the subjects running barefoot on a
treadmill, before and after 45 min of outside running wearing shoes. Both
individuals with Pes Cavus and Pes Planus showed a significant increase in the
calcaneal eversion (P<0.05) after 45 min of running. Between the groups, there
was a significantly greater eversion of the Pes Planus, on the right foot, after
45 min of running (P<0.05) compared to the Pes Cavus. The effect of fatigue
evident in the present study suggests that further biomechanical research should
be considered when exposing the foot to the repetitive nature of running,
conditions most likely responsible for the overrepresented overuse injuries among
runners.
PMID- 28503540
TI - Comparisons of incidence of spinal and lower extremity deformities according to
the physical characteristics between sports major and nonmajor college students.
AB - This research was performed to identify the incidence of spinal and lower
extremity deformity and to identify the relationship of the incidence between the
physical characteristics. One hundred forty-seven Physical Education major
students and 54 nonmajor students participated in this study. Data collecting was
performed by questionnaire and visual postural evaluation. The incidences of genu
varus (P<0.00001), genu recurvatum (P=0.0007), forward head (P<0.00001), lordosis
(P<0.00001), and scoliosis (P=0.0008) were significantly lower in non-major
students compared to major students. The incidences of genu varus (P=0.0017), leg
length discrepancy (P=0.0015), and forward head (P=0.005) were significantly
greater in women than their counterpart. However, in genu recurvatum (P<0.00001),
kyphosis (P=0.0001), and lordosis (P=0.0024), the incidences were significantly
lower in women. Overweight (body mass index [BMI]>24.5 kg/m2) students showed
significantly high incidence (4.7 times, P=0.0044) in genu varus compared to
students with normal BMI, and revealed significantly low incidence in genu
recurvatum (P=0.0047) and protruding abdomen (P=0.0002).
PMID- 28503541
TI - Effects of 12-week core stabilization exercise on the Cobb angle and lumbar
muscle strength of adolescents with idiopathic scoliosis.
AB - To identify the effects of core stabilization exercise on the Cobb angle and
lumbar muscle strength of adolescent patients with idiopathic scoliosis. Subjects
in the present study consisted of primary school students who were confirmed to
have scoliosis on radiologic examination performed during their visit to the
National Fitness Center in Seoul, Korea. Depending on whether they participated
in a 12-week core stabilization exercise program, subjects were divided into the
exercise (n=14, age 12.71+/-0.72 years) or control (n=15, age 12.80+/-0.86 years)
group. The exercise group participated in three sessions of core stabilization
exercise per week for 12 weeks. The Cobb angle, flexibility, and lumbar muscle
strength tests were performed before and after core stabilization exercise.
Repeated-measure two-way analysis of variance was performed to compare the
treatment effects between the exercise and control groups. There was no
significant difference in thoracic Cobb angle between the groups. The exercise
group had a significant decrease in the lumbar Cobb angle after exercise compared
to before exercise (P<0.001). The exercise group also had a significant increase
in lumbar flexor and extensor muscles strength after exercise compared to before
exercise (P<0.01 and P<0.001, respectively). Core stabilization exercise can be
an effective therapeutic exercise to decrease the Cobb angle and improve lumbar
muscle strength in adolescents with idiopathic scoliosis.
PMID- 28503542
TI - Role of physical activity in mortality prediction in elderly hospice patients.
AB - The prediction of life-expectancy in terminally ill patients is important both
for medical and social reasons but it is widely recognized as being inaccurate.
The aim of this study was to investigate the mortality predictors and indicators
of life extension among elderly patients in a hospice service center. In order to
determine the mortality predictors, we investigated the relationship between
patients' cognitive status using the Korean-Mini Mental State Examination &
Global Deterioration Scale (K-MMSE & GDS), the patient's physical function using
the instrumental Activities of Daily Living (ADL) score, and the patient's blood
component values. The subjects included 43 men and 57 women with a mean age of
82.4+/-8.4 years, and a mean nursing period of 11.1+/-12.2 months. These
terminally ill patients were enrolled in a cross-sectional study. All data were
collected from paper and electronic charts, and patient interviews. A simple
correlation analysis was performed to determine the relationship between the
variables and to satisfy the normal distribution (P<0.01). The results revealed
that the time of death negatively correlated with ADL score (r=-0.273, P=0.006).
However, the K-MMSE & GDS, and the values of blood component such as albumin,
gamma-glutamic transpeptidase, blood urea nitrogen, and creatinine were not
correlated with the time of death. Consequently, the ADL score might be an
important predictor of mortality and life extension in elderly patients.
Therefore, in order to improve ADL score, physical exercise and overall fitness
may be potential non-pharmacologic methods useful in preventing mortality in
elderly people.
PMID- 28503543
TI - IRAK4 Deficiency in a Patient with Recurrent Pneumococcal Infections: Case Report
and Review of the Literature.
AB - Primary immunodeficiencies are genetic defects of the innate or adaptive immune
system, resulting in a propensity to infections. The innate immune system is the
first line of defense against pathogens and is critical to recognize microbes and
start the inflammatory cascade. Sensing of microbes occurs by a number of
pathogen-recognition receptors, resulting in the activation of inflammatory
signal transduction pathways, such as the activation of NF-kappaB. Herein, we
describe a case of IRAK4 deficiency, a key signal transduction molecule of toll
like and IL-1 receptors. We highlight the complexities in diagnosis of these
disorders and review genetic defects of the NF-kappaB pathway.
PMID- 28503545
TI - Relationship of Allergy with Asthma: There Are More Than the Allergy "Eggs" in
the Asthma "Basket".
AB - Asthma and allergy share a similar and very close course, especially through
childhood. Considerable research effort has been put in untangling these
associations; however, it is now becoming obvious that this is an exceedingly
difficult task. In fact, each research breakthrough further perplexes this
picture, as we are steadily moving toward the era of personalized medicine and we
begin to appreciate that what we thought to be a single disease, asthma, is in
fact an accumulation of distinct entities. In the context of this "syndrome,"
which is characterized by several, as of yet poorly defined endotypes and
phenotypes, the question of the link of "asthma" with allergy probably becomes
non-relevant. In this review, we will revisit this question while putting the
emphasis on the multifaceted nature of asthma.
PMID- 28503544
TI - Update on Foregut Molecular Embryology and Role of Regenerative Medicine
Therapies.
AB - Esophageal atresia (OA) represents one of the commonest and most severe
developmental disorders of the foregut, the most proximal segment of the
gastrointestinal (GI) tract (esophagus and stomach) in embryological terms. Of
intrigue is the common origin from this foregut of two very diverse functional
entities, the digestive and respiratory systems. OA appears to result from
incomplete separation of the ventral and dorsal parts of the foregut during
development, resulting in disruption of esophageal anatomy and frequent
association with tracheo-oesophageal fistula. Not surprisingly, and likely
inherent to OA, are associated abnormalities in components of the enteric
neuromusculature and ultimately loss of esophageal functional integrity. An
appreciation of such developmental processes and associated defects has not only
enhanced our understanding of the etiopathogenesis underlying such devastating
defects but also highlighted the potential of novel corrective therapies. There
has been considerable progress in the identification and propagation of neural
crest stem cells from the GI tract itself or derived from pluripotent cells. Such
cells have been successfully transplanted into models of enteric neuropathy
confirming their ability to functionally integrate and replenish missing or
defective enteric nerves. Combinatorial approaches in tissue engineering hold
significant promise for the generation of organ-specific scaffolds such as the
esophagus with current initiatives directed toward their cellularization to
facilitate optimal function. This chapter outlines the most current understanding
of the molecular embryology underlying foregut development and OA, and also
explores the promise of regenerative medicine.
PMID- 28503547
TI - Theoretically Guided Analytical Method Development and Validation for the
Estimation of Rifampicin in a Mixture of Isoniazid and Pyrazinamide by UV
Spectrophotometer.
AB - A simple, rapid, economic, accurate, and precise method for the estimation of
rifampicin in a mixture of isoniazid and pyrazinamide by UV spectrophotometeric
technique (guided by the theoretical investigation of physicochemical properties)
was developed and validated. Theoretical investigations revealed that isoniazid
and pyrazinamide both were freely soluble in water and slightly soluble in ethyl
acetate whereas rifampicin was practically insoluble in water but freely soluble
in ethyl acetate. This indicates that ethyl acetate is an effective solvent for
the extraction of rifampicin from a water mixture of isoniazid and pyrazinamide.
Computational study indicated that pH range of 6.0-8.0 would favor the extraction
of rifampicin. Rifampicin is separated from isoniazid and pyrazinamide at pH 7.4
+/- 0.1 by extracting with ethyl acetate. The ethyl acetate was then analyzed at
lambdamax of 344.0 nm. The developed method was validated for linearity, accuracy
and precision according to ICH guidelines. The proposed method exhibited good
linearity over the concentration range of 2.5-35.0 MUg/mL. The intraday and inter
day precision in terms of % RSD ranged from 1.09 to 1.70% and 1.63 to 2.99%,
respectively. The accuracy (in terms of recovery) of the method varied from of
96.7 +/- 0.9 to 101.1 +/- 0.4%. The LOD and LOQ were found to be 0.83 and 2.52
MUg/mL, respectively. In addition, the developed method was successfully applied
to determine rifampicin combination (isoniazid and pyrazinamide) brands available
in Bangladesh.
PMID- 28503546
TI - Computational Tool for Fast in silico Evaluation of hERG K+ Channel Affinity.
AB - The development of a novel comprehensive approach for the prediction of hERG
activity is herein presented. Software Phase has been used to derive a 3D-QSAR
model, employing as alignment rule a common pharmacophore built on a subset of 22
highly active compounds (threshold Ki: 50 nM) against hERG K+ channel. Five
features comprised the pharmacophore: two aromatic rings (R1 and R2), one
hydrogen-bond acceptor (A), one hydrophobic site (H), and one positive ionizable
function (P). The sequential 3D-QSAR model developed with a set of 421 compounds
(randomly divided in training and test set) yielded a test set (Q2) = 0.802 and
proved to be predictive with respect to an external test set of 309 compounds
that were not used to generate the model ([Formula: see text] = 0.860).
Furthermore, the model was submitted to an in silico validation for assessing the
reliability of the approach, by applying a decoys set, evaluating the Guner and
Henry score (GH) and the Enrichment Factor (EF), and by using the ROC curve
analysis. The outcome demonstrated the high predictive power of the inclusive 3D
QSAR model developed for the hERG K+ channel blockers, confirming the fundamental
validity of the chosen approach for obtaining a fast proprietary cardiotoxicity
predictive tool to be employed for rationally designing compounds with reduced
hERG K+ channel activity at the early steps of the drug discovery trajectory.
PMID- 28503548
TI - Exploiting Self-organization in Bioengineered Systems: A Computational Approach.
AB - The productivity of bioengineered cell factories is limited by inefficiencies in
nutrient delivery and waste and product removal. Current solution approaches
explore changes in the physical configurations of the bioreactors. This work
investigates the possibilities of exploiting self-organizing vascular networks to
support producer cells within the factory. A computational model simulates de
novo vascular development of endothelial-like cells and the resultant network
functioning to deliver nutrients and extract product and waste from the cell
culture. Microbial factories with vascular networks are evaluated for their
scalability, robustness, and productivity compared to the cell factories without
a vascular network. Initial studies demonstrate that at least an order of
magnitude increase in production is possible, the system can be scaled up, and
the self-organization of an efficient vascular network is robust. The work
suggests that bioengineered multicellularity may offer efficiency improvements
difficult to achieve with physical engineering approaches.
PMID- 28503551
TI - A Case of Fibrillary Glomerulonephritis with Fibril Deposition in the Arteriolar
Wall and a Family History of Renal Disease.
AB - Herein, we report a case of fibrillary glomerulonephritis (FGN). FGN usually
shows non-amyloidal fibrils in the mesangium and glomerular capillary walls on
electron microscopy. Inherited cases of FGN have been reported in only 3
families, and the suspected genetic form was autosomal dominant. In the present
case, the deposition of microfibrils in the arteriolar wall as well as the
glomerulus is unique. Our patient's father died of nephrotic syndrome, and his
elder brother had a biopsy-proven glomerulopathy. The histological findings of
the brothers are similar to mesangial proliferative glomerulonephritis and
resemble each other. Therefore, our case is presumed to be familial FGN.
Additionally, herein, we review the literature and reconsider the histological
and clinical characters of FGN.
PMID- 28503549
TI - Learning from Mother Nature: Innovative Tools to Boost Endogenous Repair of
Critical or Difficult-to-Heal Large Tissue Defects.
AB - For repair of chronic or difficult-to-heal tissue lesions and defects, major
constraints exist to a broad application of cell therapy and tissue engineering
approaches, i.e., transplantation of "ex vivo" expanded autologous
stem/progenitor cells, alone or associated with carrier biomaterials. To enable a
large number of patients to benefit, new strategies should be considered. One of
the main goals of contemporary regenerative medicine is to develop new
regenerative therapies, inspired from Mother Nature. In all injured tissues, when
platelets are activated by tissue contact, their released factors promote innate
immune cell migration to the wound site. Platelet-derived factors and factors
secreted by migrating immune cells create an inflammatory microenvironment, in
turn, causing the activation of angiogenesis and vasculogenesis processes.
Eventually, repair or regeneration of the injured tissue occurs via paracrine
signals activating, mobilizing or recruiting to the wound site cells with healing
potential, such as stem cells, progenitors, or undifferentiated cells derived
from the reprogramming of tissue differentiated cells. This review, largely based
on our studies, discusses the identification of new tools, inspired by cellular
and molecular mechanisms overseeing physiological tissue healing, that could
reactivate dormant endogenous regeneration mechanisms lost during evolution and
ontogenesis.
PMID- 28503550
TI - Design of Surfactant Protein B Peptide Mimics Based on the Saposin Fold for
Synthetic Lung Surfactants.
AB - Surfactant protein (SP)-B is a 79-residue polypeptide crucial for the biophysical
and physiological function of endogenous lung surfactant. SP-B is a member of the
Saposin or Saposin-like proteins (SAPLIP) family of proteins that share an
overall three-dimensional folding pattern based on secondary structures and
disulfide connectivity and exhibit a wide diversity of biological functions. Here
we review the synthesis, molecular biophysics and activity of synthetic analogs
of Saposin proteins designed to mimic those interactions of the parent proteins
with lipids that enhance interfacial activity. Saposin proteins generally
interact with target lipids as either monomers or multimers via well-defined
amphipathic helices, flexible hinge domains, and insertion sequences. Based on
the known 3D-structural motif for the Saposin family, we show how bioengineering
techniques may be used to develop minimal peptide constructs that maintain
desirable structural properties and activities in biomedical applications. One
important application is the molecular design, synthesis and activity of Saposin
mimics based on the SP-B structure. Synthetic lung surfactants containing active
SP-B analogs may be potentially useful in treating diseases of surfactant
deficiency or dysfunction including the neonatal respiratory distress syndrome
and acute lung injury/acute respiratory distress syndrome.
PMID- 28503552
TI - Impact of Isolated Tricuspid Valve Repair on Right Ventricular Remodelling in an
Adult Congenital Heart Disease Population.
AB - BACKGROUND: Surgical repair of isolated congenital tricuspid valve (TV) disease
is rare with no well-defined indication and outcomes. Moreover, the role of right
ventricle (RV) in this context has not yet been investigated. OBJECTIVES: We
sought to assess the impact of congenital TV repair on cardiac remodelling and
clinical-functional status and the importance of the RV function in an adult
congenital heart disease (ACHD) population. METHODS AND RESULTS: From January
2005 to December 2015, 304 patients underwent TV surgery in our centre. Of these,
27 (ACHD) patients had isolated TV repair. Patients were evaluated with
preoperative and postoperative transthoracic echocardiogram. Survival rate has
been investigated with a mean clinical follow-up (FU) of 3.7 +/- 2.3 years,
whereas the mean echocardiographic FU was 2.9 +/- 1.8 years. The clinical and
functional status of patients showed a statistically significant improvement
after the surgical repair in terms of New York Heart Association class (66.7 vs
7.4%; p < 0.01), clinical signs of heart failure (29.6 vs 7.4%; p < 0.01), and
left ventricular function (14.8 vs 7.4%; p < 0.01). The RV and right atrium
diameter were significantly reduced after surgery (5.15 +/- 1.21 vs 4.32 +/-
1.16; p < 0.01) and (44.7 +/- 16.7 vs 26.7 +/- 9.2; p < 0.01), respectively. The
degree of postoperative pulmonary hypertension was also significantly reduced
(40.7 vs 7.4%; p < 0.01). The survival rate was 96.3% at 1 year and 93.7% at 5
years. One patient (3.7%) had early failure of the tricuspid repair requiring a
reoperation. CONCLUSION: Isolated TV repair for adult congenital disease
significantly improved patients' clinical and functional status and allowed right
ventricular remodelling and functional improvement.
PMID- 28503553
TI - Elephant-Initiated Interactions with Humans: Individual Differences and Specific
Preferences in Captive African Elephants (Loxodonta africana).
AB - South Africa has seen a recent increase in the number of African elephants
(Loxodonta africana) maintained in reserves and parks and managed in free
contact, where they may spend a significant amount of time in close proximity to
humans. This study investigates how individual elephants choose to initiate
interactions with humans by examining whether interaction types and frequencies
vary both between elephants and with regards to the category of human involved in
the interaction. Observations were made on a herd of seven captive African
elephants frequently exposed to elephant handlers (guides), volunteers (who carry
out general observations for the park's research unit), and tourists. The
elephants differed in the frequencies with which they initiated interactions with
each category of human and in the types of behaviors they used to initiate
interactions. However, all of the elephants interacted most frequently with
guides. Certain individual elephants showed preferences in interacting with
specific guides, indicating particular elephant-guide bonds. This study provides
evidence for elephant-handler bonds as well as information on the extent of
interactions between humans and African elephants managed in free contact.
PMID- 28503554
TI - Multimodality imaging of intrahepatic cholangiocarcinoma.
AB - Intrahepatic cholangiocarcinomas account for approximately 20% of cases of
cholangiocarcinomas. Three growth patterns or morphologic subtypes exist,
including mass-forming, periductal-infiltrating, and intraductal-growth subtypes.
Knowledge of these morphologic subtypes and their radiologic appearance aids in
timely diagnosis, a key to optimizing patient outcomes. The morphologic
variability of intrahepatic cholangiocarcinomas has a direct impact on the
diagnostic sensitivity and specificity of various diagnostic imaging modalities,
including ultrasound (US), computed tomography (CT), magnetic resonance imaging
(MRI)/magnetic resonance cholangiopancreatography (MRCP), and positron emission
tomography (PET). The following review emphasizes optimal imaging technique for
each of these modalities and reviews the imaging appearance of each morphologic
subtype of intrahepatic cholangiocarcinoma.
PMID- 28503557
TI - Epidemiology and risk factors: intrahepatic cholangiocarcinoma.
AB - Intrahepatic cholangiocarcinoma (ICC) is a rare entity with a distinct clinical
course and epidemiology from hilar and extrahepatic cholangiocarcinoma. ICC makes
up 8-10% of cholangiocarcinomas and 10-20% of all primary liver tumors. There
remains a considerable amount of geographic variation in the incidence of ICC
worldwide; however, the overall incidence of this malignancy appears to be
rising. Several risk factors have been identified, such as infectious causes
(liver flukes, viral hepatitis), biliary tract disease [primary sclerosing
cholangitis (PSC), hepaticolithiasis, biliary cystic diseases], metabolic
syndrome, lifestyle choices (alcohol abuse, tobacco use), and cirrhosis. Despite
this, a substantial number of ICC patients do not have any identifiable risk
factors, underlining the need for further work into the pathogenesis of this
malignancy.
PMID- 28503556
TI - Therapeutic options for intrahepatic cholangiocarcinoma.
AB - Biliary tract cancer (BTC) is a heterogeneous group of cancers, which is composed
of intrahepatic cholangiocarcinoma (ICCA), extrahepatic cholangiocarcinoma
(ECCA), gallbladder cancers and ampullary carcinomas. While all anatomic
subgroups are treated uniformly, our understanding about the pathogenesis has
allowed us to reason that each group represents a clinically and genetically
diverse disease. The majority of patients present with locally advanced or
metastatic disease, where the standard treatment is combination systemic
cytotoxic chemotherapy with gemcitabine and cisplatin. While most receive a
clinical benefit from chemotherapy, patients eventually progress where no
standardized therapies are available in the refractory setting. With the use of
next generation sequencing, we have come to understand that ICCA is a diverse
genomic disease with many actionable alterations that may serve as potential
therapeutic targets. Further studies investigating the role of novel targeted
agents (as a single agent or with combination chemotherapy) will hopefully
provide additional treatment options for this highly lethal disease.
PMID- 28503555
TI - Surgical options for intrahepatic cholangiocarcinoma.
AB - Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver
cancer, accounting for 10-15% of primary hepatic malignancy. The incidence and
cancer-related mortality of ICC continue to increase worldwide. At present,
hepatectomy is still the most effective treatment for ICC patients to achieve
long-term survival, although its overall efficacy may not be as good as that for
patients with hepatocellular carcinoma (HCC) due to the unique pathogenesis and
clinical-pathological profiles of ICC. Viral infection, lithiasis and metabolic
factors may all be associated with the pathogenesis of ICC. Poor blood supply,
cirrhosis (in rare cases), surrounding organ invasion, and lymph node/distal
metastasis have significant impacts on the selection of surgical strategies,
surgical resection rate, postoperative complications, recurrence and metastasis.
Surgical treatment for ICC includes R0 resection, lymphadenectomy, total gross
resection of the involved biliary tracts, blood vessels and surrounding tissues
in adjacent organs, and reconstruction. Postoperative adjuvant therapy and local
regional therapy after recurrence may improve survival. Liver transplantation
(LT) is reported to have a moderate treatment effect on early ICC although its
efficacy remains controversial. In this article, we reviewed the epidemiology and
staging of ICC and highlighted the selection of surgical modalities and
postoperative outcomes of ICC patients via literature review.
PMID- 28503558
TI - Management of unresectable intrahepatic cholangiocarcinoma: how do we decide
among the various liver-directed treatments?
AB - Intrahepatic cholangiocarcinoma often causes death due to obstruction of the
biliary system or interruption of the vascular supply of the liver. This fact
emphasizes the critical need for local tumor control in this disease. Successful
local tumor control has traditionally been achievable through surgical resection
for the small proportion of patients with operable tumors. Technological advances
in radiation oncology and in interventional radiology have enabled the delivery
of ablative radiation doses or other cytotoxic therapies for tumors in the liver.
In some cases, this has translated into substantial prolongation of life for
patients with this disease, but the indications for these different treatment
options are still the subject of ongoing debate. Here, we review the
technological advances and clinical studies that are changing the way
intrahepatic cholangiocarcinoma is managed, and discuss ways to achieve
individualized treatment of patients.
PMID- 28503560
TI - Green tea and the question of reduced liver cancer risk: the dawn of potential
clinical relevance?
PMID- 28503559
TI - Cell-free DNA methylation as liquid biopsy for the assessment of fibrosis in
patients with nonalcoholic steatohepatitis: a gap between innovation and
implementation.
PMID- 28503561
TI - Green tea and liver cancer.
PMID- 28503562
TI - The natural history of nonalcoholic fatty liver disease: mortality rates and
liver enzymes.
PMID- 28503563
TI - Emerging new standard for non-invasive assessment of liver disease mortality in
non-alcoholic fatty liver disease.
PMID- 28503564
TI - Modelling western dietary habits in the mouse: easier said than done.
PMID- 28503565
TI - Healthy gut microbiota can resolve undernutrition.
PMID- 28503566
TI - Determination of the Use of Lactobacillus plantarum and Propionibacterium
freudenreichii Application on Fermentation Profile and Chemical Composition of
Corn Silage.
AB - Corn was inoculated with Lactobacillus plantarum and Propionibacterium
freudenreichii subsp. shermanii either independently or as a mixture at ensiling,
in order to determine the effect of bacterial additives on corn silage quality.
Grain corn was harvested at 32-37% of dry matter and ensiled in a 4 L laboratory
silo. Forage was treated as follows: bacterial types: B0 (without bacteria
control), B1 (L. plantarum), B2 (P. freudenreichii subsp. shermanii), and B3
(combination of L. plantarum and P. freudenreichii subsp. shermanii). Each 2 kg
of chopped forage was treated with 10 mL of bacterial culture and allowed to
ferment for 27 days. The first experiment determined the most suitable wavelength
for detection of bacteria (490 nm and 419 nm for B1 and B2, resp.) and the
preferable inoculation size (1 * 105 cfu/g). The second experiment analysed the
effect of B1 and B2 applied singly or as a mixture on the fermentation
characteristics and quality of corn silage. L. plantarum alone increased crude
protein (CP) and reduced pH rapidly. In a mixture with P. freudenreichii, the
final pH was the lowest compared to other treatments. As a mixture, inclusion of
bacteria resulted in silage with lower digestibility than control. Corn silage
treated with L. plantarum or P. freudenreichii either alone or mixed together
produced desirable silage properties; however, this was not significantly better
than untreated silage.
PMID- 28503568
TI - A Novel -72 (T->A) beta-Promoter Mutation Causing Slightly Elevated HbA2 in a
Vietnamese Heterozygote.
AB - We report a novel beta+-thalassemia mutation found in a Vietnamese family. The
molecular defect T->A lies at -72 of the beta-globin gene promoter, within the
conserved CCAAT box. The index case was a 5-year-old child having red blood cells
indices close to normal and slightly increased level of HbA2 (3.96%). The
expression of the mutated beta allele was inferred by luciferase reporter assay
in K562 cells. The beta -72 determinant is the eighth beta-thalassemic mutation
identified in Vietnam and it was not previously reported in any population. The
absence of homozygous or compound heterozygous states did not allow us to
precisely predict either its clinical impact or its relevance in management
programs. Our results further underline the importance of identifying and
characterizing new or rare beta+-thalassemic alleles in carrier screening and
prenatal diagnosis.
PMID- 28503567
TI - Cognitive Impairment in Chronic Kidney Disease: Vascular Milieu and the Potential
Therapeutic Role of Exercise.
AB - Chronic kidney disease (CKD) is considered a model of accelerated aging. More
specifically, CKD leads to reduced physical functioning and increased frailty,
increased vascular dysfunction, vascular calcification and arterial stiffness,
high levels of systemic inflammation, and oxidative stress, as well as increased
cognitive impairment. Increasing evidence suggests that the cognitive impairment
associated with CKD may be related to cerebral small vessel disease and overall
impairment in white matter integrity. The triad of poor physical function,
vascular dysfunction, and cognitive impairment places patients living with CKD at
an increased risk for loss of independence, poor health-related quality of life,
morbidity, and mortality. The purpose of this review is to discuss the available
evidence of cerebrovascular-renal axis and its interconnection with early and
accelerated cognitive impairment in patients with CKD and the plausible role of
exercise as a therapeutic modality. Understanding the cerebrovascular-renal axis
pathophysiological link and its interconnection with physical function is
important for clinicians in order to minimize the risk of loss of independence
and improve quality of life in patients with CKD.
PMID- 28503569
TI - Postneonatal Mortality and Liver Changes in Cloned Pigs Associated with Human
Tumor Necrosis Factor Receptor I-Fc and Human Heme Oxygenase-1 Overexpression.
AB - Soluble human tumor necrosis factor (shTNFRI-Fc) and human heme oxygenase 1 (hHO
1) are key regulators for protection against oxidative and inflammatory injury
for xenotransplantation. Somatic cells with more than 10 copy numbers of shTNFRI
Fc and hHO-1 were employed in somatic cell nuclear transfer to generate cloned
pigs, thereby resulting in seven cloned piglets. However, produced piglets were
all dead within 24 hours after birth. Obviously, postnatal death with liver
apoptosis was reported in the higher copy number of shTNFRI-Fc and hHO-1 piglets.
In liver, the transcript levels of ferritin heavy chain, light chain,
transferrin, and inducible nitric oxide synthase were significantly highly
expressed compared to those of lower copy number of shTNFRI-Fc and hHO-1 piglets
(P < 0.05). Also, H2O2 contents were increased, and superoxide dismutase was
significantly lower in the higher copy number of shTNFRI-Fc and hHO-1 piglets (P
< 0.05). These results indicate that TNFRI-Fc and hHO-1 overexpression may
apparently induce free iron in the liver and exert oxidative stress by enhancing
reactive oxygen species production and block normal postneonatal liver
metabolism.
PMID- 28503570
TI - A Frailty Index from Next-of-Kin Data: A Cross-Sectional Analysis from the
Mexican Health and Aging Study.
AB - Objectives. To construct a frailty index from next-of-kin information of the last
year of life of community-dwelling 50 years old or older adults and test its
association with health services utilization. Methods. Cross-sectional analysis
from next-of-kin data available from the last wave of the Mexican Health and
Aging Study (MHAS). Measurements. Along with descriptive statistics, the frailty
index (FI) was tested in regression models to assess its association with adverse
outcomes previous to death: number of hospitalized days in the previous year and
number of visits to a physician in the previous year, in unadjusted and adjusted
models. Results. From a total of 2,649 individuals the mean of age was 74.8 (+/
11.4) and 56.3% (n = 1,183) were women. The mean of the FI was of 0.279 (+/-SD
0.131, R = 0.0-0.738) and distribution was biased to the right. There was a
significant association (p < 0.001) between the FI and number of hospitalized
days (beta = 45.7, 95% CI 36.1-55.4, p < 0.001) and for the number of visits to a
physician (beta = 25.93, 95% CI 19.27-32.6, p < 0.001) both models adjusted for
age and sex. Conclusion. The FI constructed with next-of-kin data showed similar
characteristics to similar indexes of older adults. It was independently
associated with health care use.
PMID- 28503572
TI - Learning Curve and Clinical Outcomes of Performing Surgery with the InterTan
Intramedullary Nail in Treating Femoral Intertrochanteric Fractures.
AB - Purpose. The purpose of this study is to evaluate the learning curve of
performing surgery with the InterTan intramedullary nail in treating femoral
intertrochanteric fractures, to provide valuable information and experience for
surgeons who decide to learn a new procedure. Methods. We retrospectively
analyzed data from 53 patients who underwent surgery using an InterTan
intramedullary nail at our hospital between July 2012 and September 2015. The
negative exponential curve-fit regression analysis was used to evaluate the
learning curve. According to 90% learning milestone, patients were divided into
two group, and the outcomes were compared. Results. The mean operative time was
69.28 (95% CI 64.57 to 74.00) minutes; with the accumulation of surgical
experience, the operation time was gradually decreased. 90% of the potential
improvement was expected after 18 cases. In terms of operative time,
intraoperative blood loss, hospital stay, and Harris hip score significant
differences were found between two groups (p = 0.009, p = 0.000, p = 0.030, and p
= 0.002, resp.). Partial weight bearing time, fracture union time, tip apex
distance, and the number of blood transfusions and complications were similar
between two groups (p > 0.5). Conclusion. This study demonstrated that the
learning curve of performing surgery with the InterTan intramedullary nail is
acceptable and 90% of the expert's proficiency level is achieved at around 18
cases.
PMID- 28503571
TI - Therapeutic Effects of Phytochemicals and Medicinal Herbs on Depression.
AB - Background. Depression is a recurrent, common, and potentially life-threatening
psychiatric disease related to multiple assignable causes. Although conventional
antidepressant therapy can help relieve symptoms of depression and prevent
relapse of the illness, complementary therapies are required due to disadvantage
of the current therapy such as adverse effects. Moreover, a number of studies
have researched adjunctive therapeutic approaches to improve outcomes for
depression patients. Purpose. One potential complementary method with
conventional antidepressants involves the use of medicinal herbs and
phytochemicals that provide therapeutic benefits. Studies have revealed
beneficial effects of medical herbs and phytochemicals on depression and their
central nervous system mechanism. Here, we summarize the current knowledge of the
therapeutic benefits of phytochemicals and medicinal herbs against depression and
describe their detailed mechanisms. Sections. There are two sections,
phytochemicals against depression and medical herbs against depression, in this
review. Conclusion. Use of phytomedicine may be an alternative option for the
treatment of depression in case conventional drugs are not applicable due to
their side effects, low effectiveness, or inaccessibility. However, the efficacy
and safety of these phytomedicine treatments for depression have to be supported
by clinical studies.
PMID- 28503573
TI - Collagen External Scaffolds Mitigate Intimal Hyperplasia and Improve Remodeling
of Vein Grafts in a Rabbit Arteriovenous Graft Model.
AB - Objectives. The aim of this study was to test the effects of collagen external
scaffold (CES) in intimal hyperplasia of vein grafts and explore its underlying
mechanisms. Methods. Thirty-six New Zealand white rabbits were randomized into no
graft group, graft group, and CES group. The rabbit arteriovenous graft model was
established. In CES group, the vein graft was wrapped around with CES. The
hemodynamic parameters of vein grafts were measured intraoperatively and 4 weeks
after operation by ultrasonic examination. Histological characteristics of vein
grafts were also evaluated 4 weeks later. The mRNA and protein levels of
proliferating cell nuclear antigen (PCNA), active cleaved-caspase-3 (ClvCasp-3),
and smooth muscle 22 alpha (SM22alpha) were measured 4 weeks later by
quantitative real-time PCR and western blot. Results. CES significantly improved
the hemodynamic stability of vein grafts, with higher blood velocity and blood
flow. Similarly, CES also markedly mitigated intimal hyperplasia and inhibited
dilatation of vein grafts. In CES group, the upexpression of PCNA and ClvCasp-3
and the downexpression of SM22alpha were inhibited. Conclusion. CES exerts
beneficial effects in mitigating intimal hyperplasia and improving remodeling of
autogenous vein grafts, which may be associated with reducing the proliferation
and apoptosis and preserving the phenotype of VSMCs.
PMID- 28503574
TI - Vitamin D Modulates Hematological Parameters and Cell Migration into Peritoneal
and Pulmonary Cavities in Alloxan-Diabetic Mice.
AB - Background/Aims. The effects of cholecalciferol supplementation on the course of
diabetes in humans and animals need to be better understood. Therefore, this
study investigated the effect of short-term cholecalciferol supplementation on
biochemical and hematological parameters in mice. Methods. Male diabetic
(alloxan, 60 mg/kg i.v., 10 days) and nondiabetic mice were supplemented with
cholecalciferol for seven days. The following parameters were determined: serum
levels of 25-hydroxyvitamin D, phosphorus, calcium, urea, creatinine, alanine
aminotransferase, aspartate aminotransferase, alkaline phosphatase, red blood
cell count, white blood cell count (WBC), hematocrit, hemoglobin, differential
cell counts of peritoneal lavage (PeL), and bronchoalveolar lavage (BAL) fluids
and morphological analysis of lung, kidney, and liver tissues. Results. Relative
to controls, cholecalciferol supplementation increased serum levels of 25
hydroxyvitamin D, calcium, hemoglobin, hematocrit, and red blood cell counts and
decreased leukocyte cell counts of PeL and BAL fluids in diabetic mice. Diabetic
mice that were not treated with cholecalciferol had lower serum calcium and
albumin levels and hemoglobin, WBC, and mononuclear blood cell counts and higher
serum creatinine and urea levels than controls. Conclusion. Our results suggest
that cholecalciferol supplementation improves the hematological parameters and
reduces leukocyte migration into the PeL and BAL lavage of diabetic mice.
PMID- 28503575
TI - Association between NLPR1, NLPR3, and P2X7R Gene Polymorphisms with Partial
Seizures.
AB - Objectives. Clinical and experimental evidence has clarified that the
inflammatory processes within the brain play a pivotal role in the
pathophysiology of seizures and epilepsy. Inflammasomes and P2X7 purinergic
receptor (P2X7R) are important mediators during the inflammatory process.
Therefore, we investigated the possible association between partial seizures and
inflammasomes NLPR1, NLRP3, and P2X7R gene polymorphisms in the present study.
Method. A total of 163 patients and 201 health controls were enrolled in this
study and polymorphisms of NLPR1, NLRP3, and P2X7R genes were detected using
polymerase chain reaction- (PCR-) ligase detection reaction method. Result. The
frequency of rs878329 (G>C) genotype with C (CG + CC) was significantly lower
among patients with partial seizures relative to controls (OR = 2.033, 95% CI =
1.290-3.204, p = 0.002 for GC + CC versus GG). Intriguingly, we found that the
significant difference of rs878329 (G>C) genotype and allele frequency only
existed among males (OR = 2.542, 95% CI = 1.344-4.810, p = 0.004 for GC + CC
versus GG), while there was no statistically significant difference among
females. However, no significant results were presented for the genotype
distributions of rs8079034, rs4612666, rs10754558, rs2027432, rs3751143, and
rs208294 polymorphisms between patients and controls. Conclusion. Our study
demonstrated the potentially significant role of NLRP1 rs878329 (G>C) in
developing susceptibility to the partial seizures in a Chinese Han population.
PMID- 28503576
TI - Sirtuin 2 Regulates Microvascular Inflammation during Sepsis.
AB - Objective. Sepsis and septic shock, the leading causes of death in noncoronary
intensive care units, kill more than 200,000/year in the US alone. Circulating
cell-endothelial cell interactions are the rate determining factor in sepsis
inflammation. Sirtuin, a seven-member family of proteins (SIRT1-7),
epigenetically controls inflammation. We have studied the roles of SIRTs 1, 3,
and 6 in sepsis previously. In this project, we studied the role of SIRT2 on
sepsis-related inflammation. Methods. Sepsis was induced in C57Bl/6 (WT), SIRT2
knockout (SIRT2KO), and SIRT2 overexpressing (SIRT2KI) mice by cecal ligation and
puncture (CLP). We studied leukocyte/platelet adhesion using intravital
microscopy and E-selectin/ICAM-1 adhesion molecule expression in the small
intestine with immunohistochemistry (IHC) six hours post-CLP/sham surgery. We
also studied 7-day survival rates in WT, SIRT2KO, and SIRT2KI sepsis mice.
Results. Compared to WT mice, SIRT2KO mice show exaggeration while SIRT2KI mice
show attenuation of cellular adhesion with sepsis in the small intestine. We also
show that the small intestinal E-selectin and ICAM-1 expressions increased in
SIRT2KO and decreased in SIRT2KI mice versus those in WT sepsis mice. We show
that the 7-day survival rate is decreased in SIRT2KO and increased in SIRT2KI
sepsis mice. Conclusion. SIRT2 modulates microvascular inflammation in sepsis and
affects survival.
PMID- 28503578
TI - Brave New World.
PMID- 28503577
TI - The Role of Proteinase-Activated Receptors 1 and 2 in the Regulation of
Periodontal Tissue Metabolism and Disease.
AB - Proteinase-activated receptors 1 (PAR1) and 2 (PAR2) are the most highly
expressed members of the PAR family in the periodontium. These receptors regulate
periodontal inflammatory and repair processes through their activation by
endogenous and bacterial enzymes. PAR1 is expressed by the periodontal cells such
as human gingival fibroblasts, gingival epithelial cells, periodontal ligament
cells, osteoblasts, and monocytic cells and can be activated by thrombin, matrix
metalloproteinase 1 (MMP-1), MMP-13, fibrin, and gingipains from Porphyromonas
gingivalis. PAR2 is expressed by neutrophils, osteoblasts, oral epithelial cells,
and human gingival fibroblasts, and its possible activators in the periodontium
are gingipains, neutrophil proteinase 3, and mast cell tryptase. The mechanisms
through which PARs can respond to periodontal enzymes and result in appropriate
immune responses have until recently been poorly understood. This review
discusses recent findings that are beginning to identify a cardinal role for PAR1
and PAR2 on periodontal tissue metabolism.
PMID- 28503579
TI - Anterior Commissure Involvement in Humanherpes Virus 6 Encephalitis.
AB - The anterior commissure is an evolutionarily conserved nerve bundle that connects
the right and left hemispheres, playing pivotal neurological roles in visual,
linguistic, and olfactory functions. The authors herein describe a 16-month-old
boy with high fever, lethargy, and recurrent seizures. Polymerase chain reaction
(PCR) examination detected human herpesvirus 6 (HHV-6) in both the cerebrospinal
fluid and the pharyngeal swabs, leading to the diagnosis of HHV-6 encephalitis.
Brain magnetic resonance imaging (MRI) 4 days after disease onset distinctly
revealed anterior commissure involvement on diffusion-weighted images and
apparent diffusion coefficient maps, suggesting that this lesion was cytotoxic
edema. After treatment with 30 mg/kg/d methylprednisolone for 3 days, the
anterior commissure involvement on MRI was completely diminished. This is the
first MRI report rarely showing anterior commissure involvement in encephalitis,
suggesting that this lesion might be caused by direct invasion of HHV-6 or
transient axonal swelling associated with inferior temporal lobe damage.
PMID- 28503581
TI - A Case Report of Homocystinuria With Dystonia and Stroke.
AB - Inherited homocystinuria is a rare autosomal recessive aminoacidopathy which
through early diagnosis can prevent its severe neurologic and vascular
complications. Here we report a 9-year-old girl with homocystinuria, presenting
with sequential symptoms of bilateral lens dislocation, skeletal complication,
and eventually dystonia from the age of 4 years. Laboratory evaluation revealed
severe high serum homocysteine level. Although pathophysiologically unexplained,
evidence of deep white matter watershed infarct along with remarkable ipsilateral
carotid stenosis was detected on the contralateral side of the dystonia in the
neuroimaging. Treatment with high dose of pyridoxine relieved limb and gait
dystonia significantly, while carotid stenosis remained unchanged. Therefore,
homocysteine might have both structural and irreversible effect and functional
and reversible impact that could be overcome even in late stages.
PMID- 28503580
TI - Connexin 43 and Its Hemichannels Mediate Hypoxia-Ischemia-Induced Cell Death in
Neonatal Rats.
AB - Wistar rat pups had the left common carotid artery cut, and they were exposed to
8% oxygen with free access to food and water until they were killed at 1, 12, 24,
and 48 hours after the hypoxia-ischemia (HI) insult. Connexin 43 (Cx43),
hemichannel (HC1), and caspase 3 (Casp3) in cerebral HI tissues were examined by
immunohistochemistry and Western blot analyses. Astrocytes cell line, astrocytes
transduced with a retroviral empty vector (Psup astrocyte), or a Cx43-specific
small hairpin RNA (shRNA) construct (shRNA astrocytes) was treated with oxygen
glucose deprivation (OGD) insult. The viability of astrocytes was assessed by 3
(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The results
showed the expression of Cx43, HC1, and Casp3 in rats' brain, and astrocytes and
Psup astrocytes increased significantly after 24 hours of HI/OGD insult. Cell
viability decreased after 24 hours of the insult. The results suggest that Cx43
and hemichannel are likely to mediate the astrocytic death after HI insult.
PMID- 28503582
TI - Neuro-Behcets in a Child.
AB - We describe a case of neuro-Behcet disease diagnosed in a 12-year-old girl. This
patient presented with recurrent oral ulcers, incontinence, spastic gait, blurry
vision, and asymmetrical lower extremity hypertonia. Extensive testing revealed
punctate lesions through the central nervous system, vitritis, papillitis, and
uveitis. A thorough infectious and neoplastic workup was negative. She was
treated with pulse steroids and azathioprine with gradual improvement in her gait
and ophthalmologic findings. Although rare, primary neuro-Behcet should be
considered in pediatric patients with neurologic abnormalities and recurrent
aphthous ulcers without other explanation.
PMID- 28503583
TI - Childhood-Onset Progressive Dystonia With Mitochondrial DNA G14459A Mutation:
Efficacy of Long-Term Sodium Succinate Treatment.
AB - This article reports the case of an 11-year-old boy with progressive dystonia
caused by the homoplasmic G14459A mitochondrial DNA mutation. The patient
presented with focal dystonia in the right upper limb at 3 years of age, which
progressed over 4 years to exhibit dystonia in both the upper and lower limbs. At
7 years of age, high signal intensity lesions in the bilateral striata and the
midbrain were observed on fluid-attenuated inversion recovery images. It was
observed on diffusion-weighted images that with time, these high signal intensity
lesions migrated from the putamen to the caudate nuclei, which closely correlated
with disease progression. Because his symptoms and abnormal magnetic resonance
imaging findings progressed despite treatment with coenzyme Q10 and l-carnitine,
at 7 years of age he was then started on sodium succinate, hoping to improve his
complex I deficiency. After treatment, progression of MRI abnormalities appeared
to have been suppressed for 4 years, although no improvement was observed in
dystonia.
PMID- 28503584
TI - Use of Magnesium Sulfate Infusion for the Management of Febrile Illness-Related
Epilepsy Syndrome: A Case Series.
AB - Febrile illness-related epilepsy syndrome is a catastrophic epileptic
encephalopathy that is highly refractory to most antiepileptic drugs leading to
high morbidity and mortality. The authors report the use of a pediatric infusion
protocol of continuous intravenous magnesium sulfate for the control of seizures
in 2 children with febrile illness-related epilepsy syndrome refractory to
multiple antiepileptic drugs in a pediatric intensive care unit of a tertiary
care children's hospital. Both patients, 2 and 16 years of age, respectively,
were treated with continuous magnesium sulfate infusion. Serum magnesium
concentrations ranging from 2.1 to 5 mmol/L were achieved. Seizure reduction and
cessation were noted in 1 patient with magnesium more than 3.0 mmol/L. No
significant adverse effects were observed. Magnesium sulfate infusions can be
safely used in pediatric refractory status epilepticus. Magnesium sulfate can be
considered in the management of children with febrile illness-related epilepsy
syndrome.
PMID- 28503585
TI - Encephalocraniocutaneous Lipomatosis: A Rare Association With Tethered Spinal
Cord Syndrome With Review of Literature.
AB - Encephalocraniocutaneous lipomatosis or Haberland syndrome is a rare, congenital
neurocutaneous syndrome. It is characterized by unilateral lipomatous hamartomata
of the scalp, eyelid, and outer globe of the eye and ipsilateral neurologic
malformations. We describe the first case from Lebanon, an infant with classical
encephalocraniocutaneous lipomatosis characterized by nevus psiloliparus,
unilateral right facial and frontal-temporal subcutaneous lipomas, alopecia,
ocular coloboma, aniridia and eyelid nodular tags, ventriculomegaly with
intracranial and intraspinal lipomas, and tethered spinal cord. We report this
case of rare association between encephalocraniocutaneous lipomatosis and
tethered spinal cord syndrome and stress on the importance of spinal cord
evaluation in encephalocraniocutaneous lipomatosis.
PMID- 28503586
TI - Spontaneous Malignant Transformation of a Pilocytic Astrocytoma of Cerebellum:
Case Report.
AB - Pilocytic astrocytoma is a slowly growing neoplasia that represents the most
frequent cerebral tumor in pediatric age. Malignant transformation is rare and it
is usually related to previous radiotherapy. The authors describe a case of a
spontaneous malignant transformation of a pilocytic astrocytoma. A 3-year-old boy
was diagnosed with a cerebellar hemisphere tumor. He was submitted to a complete
excision of the lesion, and histological findings were consistent with pilocytic
astrocytoma. It was negative for p53. Twelve years later he presented with a
local recurrence. Histopathological diagnosis was glioblastoma and it was
positive for p53. Death from disease progression occurred 16 months after the
diagnosis of glioblastoma. This case suggests that patients with pilocytic
astrocytoma need closer follow-up and further genotypic studies in order to
provide clues to clinical behavior. Such understanding can allow us to stratify
treatment accordingly and to proceed to more aggressive treatment when necessary.
PMID- 28503587
TI - Newly Identified Characteristics and Suggestions for Diagnosis and Treatment of
Diffuse Leptomeningeal Glioneuronal/Neuroepithelial Tumors: A Case Report and
Review of the Literature.
AB - Diffuse leptomeningeal glioneuronal tumor is unique for communicating
hydrocephalus, diffuse leptomeningeal enhancement, cystic changes, absence of
tumor cells in cerebral spinal fluid, and a cell population of both glial and
neuronal copositivity. It has likely been misdiagnosed as mixed glioneuronal
tumors, oligodendrogliomas, and neuroepithelial tumors. Children with signs of
this tumor are often worked up for infection, rheumatologic disease, or
disseminated primary malignancy, resulting in unnecessary testing and treatment.
We describe a 14-year-old female with recurrent headaches, hydrocephalus, and
diffuse leptomeningeal enhancement discovered to be neoplastic 1 year after
initial presentation, owing to extensive and unrevealing infectious and
immunologic workups. Biopsies revealed atypical cells with markers of both glial
and neuronal cells, positivity for OLIG-2, and focal p53 positivity. Great
response was seen with temozolomide and craniospinal irradiation. Additionally,
we postulate additional diagnostic indicators that may aid in earlier diagnosis
and treatment decisions.
PMID- 28503588
TI - Arthrogryposis Multiplex Congenita Related to Third-Trimester Basal Ganglia
Ischemia: A Case Report.
AB - Arthrogryposis multiplex congenita is a syndromic condition defined by
contracture of 2 or more joints. A large range of etiologies has been reported
such as neuromuscular disorders (peripheral dysfunction), chromosomal
abnormalities, or cerebral malformations (central dysfunction) leading to fetal
immobility. Severity of arthrogryposis depends on the etiology and duration of
fetal immobility. The authors report a 34 gestational weeks infant presenting
with severe diffuse arthrogryposis symptoms and respiratory failure at birth. Her
mother experienced cardiac arrest at 29 gestational weeks due to carbon monoxide
intoxication. Fetal magnetic resonance imaging revealed extensive corticospinal
tract lesions. Antenatal ischemia of the deep gray matter needs to be considered
as a possible arthrogryposis cause.
PMID- 28503589
TI - FOXG1 Mutation is a Low-Incidence Genetic Cause in Atypical Rett Syndrome.
AB - Due to the genetic and clinical heterogeneity of Rett syndrome, patients with
nonclassic phenotypes are classified as an atypical Rett syndrome, that is,
preserved speech variant, early seizure variant, and congenital variant.
Respectively, MECP2, CDKL5, and FOXG1 have been found to be the causative genes,
but FOXG1 variants are the rarest and least studied. We performed mutational
analyses for FOXG1 on 11 unrelated patients without MECP2 and CDKL5 mutations,
who were diagnosed with atypical Rett syndrome. One patient, who suffered from
severe early-onset mental retardation and multiple-type intractable seizures,
carried a novel, de novo FOXG1 mutation (p.Gln70Pro). This case concurs with
previous studies that have reported yields of ~10%. FOXG1-related atypical Rett
syndrome is rare in Korean population, but screening of this gene in patients
with severe mental retardation, microcephaly, and early-onset multiple seizure
types without specific genetic causes can help broaden the phenotypic spectrum of
the distinct FOXG1-related syndrome.
PMID- 28503590
TI - Clinical Phenotype of De Novo GNAO1 Mutation: Case Report and Review of
Literature.
AB - Mutations in the guanine nucleotide-binding protein (G protein), alpha activating
activity polypeptide O (GNAO1) gene have recently been described in 6 patients
with early infantile epileptic encephalopathies. In the present study, we report
the phenotype and the clinical course of a 4-year-old female with an epileptic
encephalopathy (Ohtahara syndrome) and profound intellectual disability due to a
de novo GNAO1 mutation (c.692A>G; p.Tyr231Cys). Ohtahara syndrome is a
devastating early infantile epileptic encephalopathy that can be caused by
mutations in different genes, now also including GNAO1. The mutation was found
using a targeted next generation sequencing gene panel and demonstrates targeted
sequencing as a powerful tool for identifying mutations in genes where only a few
de novo mutations have been identified.
PMID- 28503591
TI - Prevalence and Characteristics of Chinese Patients With Duchenne and Becker
Muscular Dystrophy: A Territory Wide Collaborative Study in Hong Kong.
AB - The aim of this collaborative study on Duchenne muscular dystrophy and Becker
muscular dystrophy is to determine the prevalence and to develop data on such
patients as a prelude to the development of registry in Hong Kong. Information on
clinical and molecular findings, and patient care, was systematically collected
in 2011 and 2012 from all Pediatric Neurology Units in Hong Kong. Ninety patients
with dystrophinopathy were identified, and 83% has Duchenne muscular dystrophy.
The overall prevalence of dystrophinopathy in Hong Kong in 2010 is 1.03 per 10
000 males aged 0 to 24 years. Among the Duchenne group, we observed a higher
percentage (40.6%) of point mutations with a lower percentage (45.3%) of exon
deletions in our patients when compared with overseas studies. Although we
observed similar percentage of Duchenne group received scoliosis surgery,
ventilation support, and cardiac treatment when compared with other countries,
the percentage (25%) of steroid use is lower.
PMID- 28503592
TI - Ictal 99mTc-Ethyl Cysteinate Dimer SPECT Findings of a Girl With Refractory
Localization-Related Epilepsy Who Developed Transient Ictal Bradycardia.
AB - Ictal bradycardia, which is considered to be one of the causes of sudden
unexplained death in epilepsy, is rare. A 10-year-old girl with focal cortical
dysplasia in her right centroparietal region developed transient ictal
bradycardia during cluster seizures. Brain magnetic resonance imaging
demonstrated a high signal intensity lesion adjacent to the focal cortical
dysplasia lesion. Ictal 99mTc-ethyl cysteinate dimer single-photon emission
computed tomography (SPECT) detected hyperperfusion in an area containing the
high signal intensity lesion, which was located close to the insular cortex.
Since the hyperperfusion zone observed on SPECT was considered to reflect seizure
propagation, it is possible that the ictal bradycardia experienced in the present
case was caused by the following mechanism: The repetitive seizure activity
caused the high-intensity lesion seen on MRI to expand into the right insular
cortex, which controls cardiac rhythm, resulting in ictal bradycardia.
PMID- 28503593
TI - Transient Cerebral Arteriopathy in a Child Associated With Cytomegalovirus
Infection.
AB - Vascular wall injuries account for up to 80% of childhood strokes, excluding
emboli of cardiac origin. Transient cerebral arteriopathy is a recently described
entity that is increasingly recognized as an important cause. The cerebral
arterial wall is thought to be affected by an inflammatory process related to
certain infections. The authors report a 2.5-year-old girl with sudden left
hemiplegia and aphasia. The neuroimaging showed occlusion of the right middle
cerebral artery and ischemic damages. Laboratory revealed positive
cytomegalovirus immunoglobulin M and G in cerebrospinal fluid and in early and
late sera. Treatment with ganciclovir, anticytomegalovirus immunoglobulin, and
prednisolone, followed by oral aspirin, resulted in clinical improvement. The
follow-up neuroimaging showed stabilization of the arterial lesions without
residual stenosis. To our knowledge, this is the first report of a
cytomegalovirus-associated transient cerebral arteriopathy in an immunocompetent
child. Our report demonstrates the propensity for cytomegalovirus to be involved
in pediatric cerebral vascular disease.
PMID- 28503594
TI - First Application of Ketogenic Diet on a Child With Intractable Epilepsy in
Ghana.
AB - The prevalence of epilepsy in sub-Saharan Africa is higher than in other parts of
the world, but it is short of the effective measure on treating intractable
epilepsy. Epilepsy surgery is not easy to be performed due to the high cost and
demand of operational skills. The authors planned to perform ketogenic diet
therapy for the children with intractable epilepsy in Ghana with regard to its
low cost and simple procedure. The candidate is a 10-month-old girl with epilepsy
with unknown etiology. Her seizures couldn't be controlled by more than 3
antiepileptic drugs. Her development delayed severely due to frequent seizures.
The authors successfully applied ketogenic diet for her. Her seizures were
completely controlled after 2 weeks' therapy. Her mental condition was improved
after that. The authors get much experience from this case for further developing
ketogenic diet in Africa. This is the first report that ketogenic diet was
applied to control intractable epilepsy in West Africa.
PMID- 28503596
TI - Guillain Barre Syndrome in a Child With X-Linked Adrenoleukodystrophy.
AB - X-Linked adrenoleukodystrophy is the most common peroxisomal disorder with
different phenotypes among patients carrying the same ABCD1 mutation. There were
previously reported associations of X-linked adrenoleukodystrophy with autoimmune
disorders. The authors describe Guillain Barre syndrome in a child with X-linked
adrenoleukodystrophy. The available evidence does not permit conclusion
concerning etiological linkage between the 2 diseases, but it warrants further
study.
PMID- 28503595
TI - A New Observation of an Atypical and Severe Variant of the Guillain-Barre
Syndrome in a Child: Remaining Challenges for Diagnosis, Nosologic
Classification, and Therapeutic Course.
AB - Guillain-Barre syndrome is a rare acute polyradiculoneuropathy. Several variants
and unusual presentations have been described, particularly in pediatrics. In
most cases, making an early diagnosis is challenging due to the treatments that
consist in the rapid administration of intravenous immunoglobulin or plasma
exchange. The authors present the case of a 7-year-old boy with an atypical and
severe axonal Guillain-Barre syndrome, associated with Mycoplasma pneumonia. When
he was admitted, febrile respiratory failure was the main focus, and then he
presented signs of acute polyneuropathy with cranial nerve palsy and brief
hyperreflexia. Mechanical ventilation was required for 48 days as well as 2
cycles of intravenous immunoglobulin. The authors describe all the medical
challenges that the authors encountered. This case highlights the fact that
respiratory distress can be the main clinical symptom in children. This delays
the establishment of a correct diagnosis, even more so when neurological
manifestations are abundant and unusual.
PMID- 28503597
TI - Vagal Nerve Stimulation in the Treatment of Drug-Resistant Epileptic
Encephalopathies in Inborn Errors of Metabolism: Report of 2 Cases.
AB - Patients affected by inborn errors of metabolism can develop catastrophic
epilepsies ineligible for resective surgery. Few reports concerning vagal nerve
stimulation in patients with epileptic encephalopathy in the context of metabolic
diseases have been published in the literature. Drug-resistant epilepsies in
metabolic disease could be a specific target for vagal nerve stimulation,
although the efficacy of this technique in these patients still needs to be
proved. The authors report our experience in treating refractory epilepsy with
vagal nerve stimulation in 2 patients affected by inborn errors of metabolism.
The first patient is a 23-year-old patient affected by glutaric aciduria type II,
the other one is a 16-month-old child with nonketotic hyperglycinemia. Vagal
nerve stimulation reduced seizures up to 50% in the first case and up to 90% in
the second one.
PMID- 28503598
TI - Assessing Children With Disabilities Using WHO International Classification of
Functioning, Disability and Health Child and Youth Version Activities and
Participation D Codes.
AB - AIM: Evaluation of the International Classification of Functioning, Disability
and Health child and youth version (ICF-CY) activities and participation d code
functions in clinical practice with children across diagnoses, disabilities,
ages, and genders. METHODS: A set of 57 codes were selected and worded to
describe children's support needs in everyday life. Parents of children aged 1 to
15 years participated in interviews to discuss and rate their child's disability.
RESULTS: Of 367 invited parents, 332 (90.5%) participated. The mean age of their
children with disability was 9.4 years. The mean code scores were 50.67, the
corrected code-total correlations were .76, intercode correlations had the mean
of 0.61, and Cronbach's alpha was .98. As a result of Rasch analysis, graphical
data for disability measures paralleled clinical expectations across the total
population of 332 children. CONCLUSION: The World Health Organization
International Classification of Functioning, Disability and Health child and
youth version d code data can provide a coherent measure of severity of
disability in children across various diagnoses, ages, and genders.
PMID- 28503599
TI - Is Chromosome 15q13.3 Duplication Involving CHRNA7 Associated With Oral Clefts?
AB - Copy number variants have been associated with intellectual disability, multiple
congenital anomalies and craniofacial disorders. It has been reported that
microduplication of 15q13.3 is associated with autism, cognitive impairment,
seizures, and attention-deficit hyperactivity disorder. Here, the author
identified microduplications in the 15q13.3 region in 4 cases from 3 Chinese
families using chromosomal microarray analysis-single nucleotide polymorphism
array (CMA-SNP). These 4 cases include 2 fetuses from 2 unrelated families and a
father and a daughter from a third family. The identified microduplications of
15q13.3 are approximately 400 kb in size, encompassing just 1 gene, cholinergic
receptor, neuronal nicotinic, alpha polypeptide 7 (CHRNA7). Three-fourths of the
probands exhibit oral clefts, which has not been previously reported in cases
with this duplication genotype. Therefore, in this study, the author describes
for the first time the common feature of oral clefts in patients carrying a
microduplication of 15q13.3 encompassing the CHRNA7 gene, which sheds light on
the correlation between CHRNA7 and cleft palate.
PMID- 28503600
TI - Delayed Effects of Transcutaneous Organophosphate Poisoning in Four Children.
AB - Contamination or transcutaneous absorption of organophosphates (OP) is rare and
there exist only few reports of such manner of poisoning. We report four children
from the same family in whom temporal proximity of the disease onset, a detailed
interrogation of parents and exclusion of other clinical differentials, led to
the diagnosis of transcutaneous intoxication with organophosphates (diazinon).
The contamination occurred during the game with a freshly used poison can.
Uncommon clinical picture was marked by delayed signs predominantly reflecting
certain nicotinic effects (muscle weakness, cramps) along with subtle neuropathic
features occurring throughout a few weeks after initial event. Our illustrative
cases can further contribute to the better awareness and understanding of
variable spectrum of transcutaneous route of OP poisoning.
PMID- 28503601
TI - Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis and Guillain
Barre Syndrome in a 16-Month-Old Child.
AB - A 16-month-old girl was diagnosed with Epstein-Barr virus hemophagocytic
lymphohistiocytosis and transferred to our hospital on the 58th day of the
hemophagocytic lymphohistiocytosis after treatment failure according to the
Hemophagocytic Lymphohistiocytosis-2004 protocol. On admission to our hospital,
she had a flaccid paralysis of her lower limbs. Nerve conduction studies showed a
acute motor axonal neuropathy, and a diagnosis of Guillain-Barre syndrome was
established. Intravenous immunoglobulin G was started on the 57th day of the
Guillain-Barre syndrome. To date, her neurological recovery is incomplete. For
hemophagocytic lymphohistiocytosis, after treatment failure of THP-COP regimen
(pirarubicin, cyclophosphamide, vincristine, and prednisone) and 2 courses of
ESCAP regimen (etoposide, prednisone, cytarabine, L-asparaginase), we are now in
the process of coordinating unrelated umbilical cord blood transplantation. To
the best of our knowledge, we report the youngest case of Guillain-Barre syndrome
accompanied by Epstein-Barr virus hemophagocytic lymphohistiocytosis. Rapid
progression of Guillain-Barre syndrome, the electrophysiological subtype of
Guillain-Barre syndrome, and treatment delay possibly led to poor neurological
outcome.
PMID- 28503602
TI - Clinical Profile of Pediatric Neurological Disorders: Outpatient Department,
Khartoum, Sudan.
AB - BACKGROUND: There is no available data from Sudan reflecting the magnitude of the
neurological disorders and disabilities in the pediatric age-group. This study
aims to evaluate the pattern of neurological disorders among Sudanese children.
PATIENTS AND METHODS: This is a retrospective survey of children with epilepsy
and other neurodisability disorders seen at pediatric neurology outpatient
clinic, during the period from January 2007 to August 2013. The data of 9600
patients were analyzed. RESULTS: A total of 6019 patients were included in the
study. The majority of the patients had epilepsy that amounted to 52.8%, followed
by cerebral palsy (19.1%), congenital anomalies of the central nervous system
(6.2%), neuromuscular disorders (3.2%), stroke (2.4%), ataxia and movement
disorders (1.9%), assumed genetic syndromes (1.2%), and others. CONCLUSION:
Neurological disorders constitute a major cause of chronic morbidity in pediatric
age-group.
PMID- 28503603
TI - Vein of Galen Aneurysmal Malformation in Neonates Presenting With Congestive
Heart Failure.
AB - The authors report the case of a neonate presenting with signs of a congenital
cardiac disease. Echocardiography showed a structural normal heart, right-to-left
ductal flow, a dilated superior caval vein, and reversed diastolic flow in the
proximal descending aorta. Brain magnetic resonance imaging showed a vein of
Galen arteriovenous malformation. This highlights the importance of considering
an intracranial cause in the differential diagnosis of neonatal congestive heart
failure.
PMID- 28503604
TI - A De Novo Mutation in MTND6 Causes Generalized Dystonia in 2 Unrelated Children.
AB - Dystonia is often associated with the symmetrical basal ganglia lesions of Leigh
syndrome. However, it has also been associated with mitochondrial ND mutations,
with or without Leber hereditary optic neuropathy. The m.14459G>A mutation in ND6
causes dystonia with or without familial Leber hereditary optic neuropathy. We
report heteroplasmic 14459G>A mutations in 2 unrelated children with
nonmaternally inherited generalized dystonia and showing bilateral magnetic
resonance imaging lesions in nucleus pallidus and putamen. Both children have
reached their teenage years, and they are intellectually active, despite their
motor problems.
PMID- 28503605
TI - Chromosome 12p Deletion Spanning the GRIN2B Gene Presenting With a
Neurodevelopmental Phenotype: A Case Report and Review of Literature.
AB - The GRIN2B (glutamate receptor, ionotropic, N-methyl-d-aspartate 2B) gene,
located in the short arm of chromosome 12, encoding the NR2B subunit of the N
methyl-D-aspartate receptor, has recently been recognized to play an important
role in corticogenesis and brain plasticity. Deletions in the short arm of
chromosome 12 are rare. Hemizygous loss of function of the GRIN2B gene results in
developmental delay, whereas gain of function leads to epilepsy, and infantile
spasms in particular. In addition, GRIN2B variants have been associated with
autism spectrum disorder and schizophrenia. Here the authors report a child with
global developmental delay, autistic behavioural features, central hypotonia,
dysmorphic features and isolated congenital anomalies of the fingers and toes,
and a de novo heterozygous deletion in chromosome locus 12p13.2-p13.1, involving
loss of several genes, including GRIN2B. This report and our review of the
literature help clarify the distinct phenotypes associated with loss or gain of
GRIN2B function.
PMID- 28503607
TI - Encephalopathy and Axonal Neuropathy Associated With Mycoplasma Pneumoniae
Infection: Response to Intravenous Immunoglobulin Therapy.
AB - Mycoplasma pneumoniae infection frequently presents as a self-limited process,
however, severe cases and even fatalities have been reported. The authors present
a case of Mycoplasma pneumoniae infection associated with both encephalopathy and
peripheral neuropathy that responded to intravenous immunoglobulin therapy. To
our knowledge, this is the first documented case of Mycoplasma pneumoniae related
to encephalitis and peripheral axonal neuropathy. To date, there is insufficient
data on the effect of intravenous immunoglobulin on the course of mycoplasma
associated central nervous system/peripheral nervous system disease. While
intravenous immunoglobulin has aided in a variety of autoimmune-mediated
disorders, its efficacy in mycoplasma-mediated encephalitis treatment remains
unclear. In this patient case, reversal of both central and peripheral nervous
system symptoms after treatment with intravenous immunoglobulin suggested a
possible therapeutic benefit.
PMID- 28503606
TI - MECP2 Duplications in Symptomatic Females: Report on 3 Patients Showing the Broad
Phenotypic Spectrum.
AB - Xq28 microduplications including the MECP2 gene constitute a 100% penetrant X
linked syndrome in males caused by overexpression of normal MeCP2 protein. A
small number of cases of affected females have been reported. This can be due to
the location of the duplicated material into an autosome, but it can also be due
to the location of the duplicated material into one of the X chromosomes and
random or unfavorable skewed X chromosome inactivation, which is much more likely
to occur but may be underdiagnosed because of the resulting broad phenotypic
spectrum. In order to contribute to the phenotypic delineation of Xq28
microduplications including MECP2 in symptomatic females, the authors present
clinical and molecular data on 3 patients illustrating the broad phenotypic
spectrum. Our finding underlines the importance of quantitative analysis of MECP2
in females with intellectual disability and raises the question of the indication
in females with borderline intellectual performances or learning difficulties.
PMID- 28503608
TI - Brain Inflammation in an Infant With Hemimegalencephaly, Escalating Seizures, and
Epileptic Encephalopathy.
AB - Hemimegalencephaly, a congenital brain malformation typically characterized by
enlargement of one hemisphere, is frequently associated with intractable
epilepsy. The authors report a case of a 12-month-old girl with
hemimegalencephaly who underwent semiurgent hemispherectomy because of rapidly
escalating seizures, arrested development, and associated encephalopathy. The
brain tissue was examined and evaluated for neuroinflammation.
Immunohistochemical analysis of the brain tissue revealed the presence of
abundant activated CD68-positive microglia and reactive astrogliosis. Detection
of active inflammatory changes in the brain of a patient with hemimegalencephaly
complicated by intractable epilepsy suggests a potential role of ongoing brain
inflammation in seizure exacerbation and epileptic encephalopathy.
PMID- 28503609
TI - An Unusual Triad in Pediatric Neurology: A Case Report on Cerebral Palsy,
Epilepsy, and Duchenne Muscular Dystrophy.
AB - We present a case of an unusual triad in pediatric neurology: a currently 12-year
old boy with cerebral palsy and epilepsy who was later also diagnosed with
Duchenne muscular dystrophy. We describe the clinical path that resulted in this
exceptional diagnosis. This case report illustrates how different neurological
disorders may overshadow each other. In addition, it demonstrates that every
child with cerebral palsy and either an atypical clinical course or with
inexplicable laboratory values-as well as every infant boy born to a theoretical
Duchenne muscular dystrophy carrier-should be subjected to additional
investigations.
PMID- 28503610
TI - Assessment of Subclinical Pancreatitis in Epileptic Children With Different
Treatment Modalities.
AB - Acute pancreatitis differ in pediatrics and adults. Drug-induced pancreatitis is
one of the common causes of pancreatitis in children. This case-control study
aimed to assess subclinical pancreatitis in patients with epilepsy treated with
different drug regimens. Eighty known patients with epilepsy were enrolled. Forty
patients were treated with monotherapy (group I) and 40 were treated with
multitherapy (group II) regimens. Twenty age- and sex-matched healthy children
were enrolled as control (group III). Serum lipase and amylase were assayed in
all included children. Significant differences were found between groups I and
III and between groups II and III regarding serum amylase and lipase (P < .001
for all). Significant difference were found between groups I and II (P = .024)
and between groups II and III (P = .01) regarding pancreatic duct and body
diameters. Significant difference were found between patients with controlled and
uncontrolled fits regarding serum amylase (P = .008). In conclusion, subclinical
pancreatitis can complicate the treatment with different antiepileptic regimens.
PMID- 28503611
TI - Acute Postviral Encephalopathy: Pathologic and Radiologic Correlation in an
Atypical Case.
AB - The authors report a case of fatal acute encephalopathy following influenza
infection, with slightly atypical pathological and imaging findings. A healthy 8
year-old boy with probable recent influenza A/B infection admitted for refractory
seizures was placed on phenobarbital coma and later developed hemodynamic
instability. Magnetic resonance imaging revealed bilateral cerebral and
cerebellar white matter lesions and microhemorrhages. Following his demise, the
autopsy revealed a large area of necrosis in the right centrum semiovale with
similar lesions in the temporal and cerebellar regions. Microscopically, there
was extensive coagulative necrosis, compatible with necrotizing white matter
encephalopathy, and neuronal loss suggesting superimposed hypoxic-ischemia. The
acute progressive neurologic deterioration was partly reminiscent on acute
necrotizing encephalopathy, a condition recently associated with influenza A. In
acute necrotizing encephalopathy, typical brain findings are characterized by
bilateral thalamic necrosis/petechiae with variable white matter edema. The
somewhat atypical findings in our case can relate to superadded cardiovascular
collapse and hypoxic-ischemic effects.
PMID- 28503612
TI - A Video Report of Brain-Lung-Thyroid Syndrome in a Japanese Female With a Novel
Frameshift Mutation of the NKX2-1 Gene.
AB - Benign hereditary chorea is a rare autosomal-dominant disorder that is
characterized by childhood-onset nonprogressive chorea and normal cognitive
function. Defects in NKX2-1 on chromosome 14q13, which encodes thyroid
transcription factor 1, produce a concurrent clinical manifestation of chorea,
respiratory distress, and hypothyroidism known as "brain-lung-thyroid syndrome."
Here, the authors describe a video report of benign hereditary chorea in a
Japanese female with a novel frameshift mutation of NKX2-1 (c.915_916insC)
(p.Ala303ArgfsX132) that was initially misdiagnosed as ataxic cerebral palsy. In
early infancy, especially before the appearance of chorea, benign hereditary
chorea can be misdiagnosed as ataxic and dyskinetic cerebral palsy due to shared
clinical features including motor delay, hypotonia, ataxic gait, and dystonia.
PMID- 28503613
TI - A Mutation in the Tubulin-Encoding TUBB3 Gene Causes Complex Cortical
Malformations and Unilateral Hypohidrosis.
AB - Recent studies have emphasized the association between tubulin gene mutations and
developmental abnormalities of the cortex. In this study, the authors identified
a mutation in the tubulin-encoding class III beta-tubulin (TUBB3) gene in a 4
year-old boy presenting with brain abnormalities and unilateral hypohidrosis. The
patient showed a left internal strabismus, moderate developmental delay, and
congenital hypohidrosis of the right side of the body. Magnetic resonance imaging
disclosed gyral disorganization mainly in the left perisylvian region, dysmorphic
and hypertrophic basal ganglia with fusion between the putamen and caudate
nucleus without affecting the anterior limb of the internal capsule, and moderate
hypoplasia of the right brain stem and cerebellum. Diffusion tensor imaging
studies revealed disorganization of the pyramidal fibers. The amplitude of the
sympathetic skin response was low in the right arm, which led to a diagnosis of
focal autonomic neuropathy. Sequencing the TUBB3 gene revealed a de novo missense
mutation, c.862G>A (p.E288K).
PMID- 28503614
TI - De Novo 3q22.3q24 Microdeletion in a Patient With Blepharophimosis-Ptosis
Epicanthus Inversus Syndrome, Dandy-Walker Malformation, and Wisconsin Syndrome.
AB - Interstitial deletions affecting the long arm of chromosome 3 have been
associated with a broad phenotype. This has included the features of
blepharophimosis-ptosis-epicanthus inversus syndrome, Dandy-Walker malformation,
and the rare Wisconsin syndrome. The authors report a young female patient
presenting with features consistent with all 3 of these syndromes. This has
occurred in the context of a de novo 3q22.3q24 microdeletion including FOXL2,
ZIC1, and ZIC4. This patient provides further evidence for the role of ZIC1 and
ZIC4 in Dandy-Walker malformation and is the third reported case of Dandy-Walker
malformation to have associated corpus callosum thinning. This patient is also
only the seventh to be reported with the rare Wisconsin syndrome phenotype.
PMID- 28503615
TI - Neural Correlates of Reward Processing in Typical and Atypical Development.
AB - Atypically developing children including those born preterm or who have autism
spectrum disorder can display difficulties with evaluating rewarding stimuli,
which may result from impaired maturation of reward and cognitive control brain
regions. During functional magnetic resonance imaging, 58 typically and
atypically developing children (6-12 years) participated in a set-shifting task
that included the presentation of monetary reward stimuli. In typically
developing children, reward stimuli were associated with age-related increases in
activation in cognitive control centers, with weaker changes in reward regions.
In atypically developing children, no age-related changes were evident.
Maturational disturbances in the frontostriatal regions during atypical
development may underlie task-based differences in activation.
PMID- 28503616
TI - Pediatric Hereditary Neuralgic Amyotrophy: Successful Treatment With Intravenous
Immunoglobulin and Insights Into SEPT9 Pathogenesis.
AB - Hereditary neuralgic amyotrophy is a rare disorder characterized by the sudden
onset of recurrent episodes of painful brachial plexus neuropathies, followed by
atrophy within a few weeks. The authors present the case of a 5-year-old boy who
developed hereditary neuralgic amyotrophy in the right upper limb after a
gastroenteritis illness. He made a full and rapid recovery with the use of
intravenous immunoglobulin. A subsequent episode in the left upper limb during
the course of intravenous immunoglobulin was significantly attenuated. A de novo
c.262C>T mutation in exon 2 of the SEPT9 gene was identified. To our knowledge,
he is the first pediatric patient with SEPT9 hereditary neuralgic amyotrophy to
be treated with intravenous immunoglobulin. The authors hypothesize that the
c.262C>T mutation in exon 2 of the SEPT9 gene generates pathology via the
numerous isoforms under specific conditions and that intravenous immunoglobulin
can play a role at the epigenetic level of improving dysfunctional SEPT9
expression.
PMID- 28503617
TI - Further Validation of the SIGMAR1 c.151+1G>T Mutation as Cause of Distal
Hereditary Motor Neuropathy.
AB - Distal hereditary motor neuropathies represent a group of rare genetic disorders
characterized by progressive distal motor weakness without sensory loss. Their
genetic heterogeneity is high and thus eligible for diagnostic whole exome
sequencing. The authors report successful application of whole exome sequencing
in diagnosing a second consanguineous family with distal hereditary motor
neuropathy due to a homozygous c.151+1G>T variant in SIGMAR1. This variant was
recently proposed as causal for the same condition in a consanguineous Chinese
family. Compared to this family, the Afghan ethnic origin of our patient is
distinct, yet the features are identical, validating the SIGMAR1 deficiency
phenotype: progressive muscle wasting/weakness in lower and upper limbs without
sensory loss. Rapid disease progression during adolescent growth is similar and
may be due to SIGMAR1's role in regulating axon elongation and tau
phosphorylation. Finally, the authors conclude that SIGMAR1 deficiency should be
added to the differential diagnosis of distal hereditary motor neuropathies.
PMID- 28503618
TI - Occipital Bony Abnormality and Multiple Strokes in a Pediatric Patient: Case
Report and Review of the Current Literature.
AB - This study presents a case of a 15-year-old boy who had a right vertebral artery
dissection with distal embolization from repeated trauma from an occipital bony
spicule. The authors hypothesize that this bony spicule was contacting the left
vertebral artery during head rotation, resulting in trauma to the vessel and
formation of emboli which then showered distally, causing strokes in the
posterior circulation of the brain. This specific phenomenon has previously been
reported three times, only one of which was in pediatric literature. It is
important for individuals to be aware of this rare anatomic cause of vertebral
artery dissection in patients presenting with an odd constellation of symptoms
related to strokes from vertebro-basilar system. Treatment options including
early intervention with intravascular coil embolization are also discussed.
PMID- 28503619
TI - Seizures Related to Hypomagnesemia: A Case Series and Review of the Literature.
AB - OBJECTIVE: Childhood seizures have various nonneurological etiologies. The
patient's magnesium levels should be measured when evaluating afebrile seizures.
The purpose of the current case series is to describe a systematic approach for
diagnosing hypomagnesemia using 3 recent patient cases. METHODS: This case series
describes 3 patients with unprovoked hypomagnesemia-associated seizures. The
authors describe the differential diagnosis, pathophysiology, and the workup of
hypomagnesemia-associated seizures. RESULTS: Hypomagnesemia contributed to the
cause of the seizures in all 3 cases. Various causes of hypomagnesemia were
investigated, including genetic etiologies. All 3 patients were maintained at a
magnesium level >0.65 mmol/L, which improved or eliminated the seizures.
SIGNIFICANCE: Magnesium levels should always be measured when trying to determine
the etiology of seizures. Hypomagnesemia and afebrile seizures should be treated
with the goal of maintaining a magnesium concentration >0.65 mmol/L. Although
rare, genetic causes of hypomagnesemia should be considered, once common causes
of hypomagnesemia are ruled out.
PMID- 28503620
TI - Complex Phenotype of a Boy With De Novo 16p13.3-13.2 Interstitial Deletion.
AB - Interstitial deletions encompassing chromosome 16p13.3-13.2 are rarely described
in the literature, whereas terminal deletions or duplications involving this
region are slightly more frequently described. The authors describe a boy
harboring a de novo 16p13.3-13.2 interstitial deletion, with intellectual
disability, verbal dyspraxia, epilepsy, and a distinctive brain magnetic
resonance finding, namely a nodular heterotopia. The authors found partial
genotype-phenotype correspondences regarding epilepsy and intellectual
disability, which have been associated with 16p1 region. Conversely, nodular
heterotopia and verbal dyspraxia have not been clearly related to this region.
These data are in agreement with the emerging concept that similar copy number
variants may be the general risk factors for distinct disorders. Verbal
dyspraxia, which has not responded to speech therapy, is the child's most
disabling trait. In view of the above, genetic studies should be appraised in
cases of serious speech difficulties, especially if they are associated with
intellectual disability and epilepsy.
PMID- 28503621
TI - Pelvic-Spinal Analysis and the Impact of Onabotulinum toxin A Injections on
Spinal Balance in one Child With Cerebral Palsy.
AB - BACKGROUND: In children with cerebral palsy, primary (eg, abnormal muscle tone
and weakness) and secondary impairments (eg, contractures) can modify pelvic
spinal alignment. The main aim of this article was to establish a new approach to
pelvic-spinal analysis in children with cerebral palsy, taking into account the
whole pelvis-spine complex, illustrated by a case study. METHODS: This is a case
study of an ambulatory child with cerebral palsy (spastic diplegia) who underwent
analysis of the pelvic-spine complex from X-ray images taken in standing position
from C2 to the proximal femur. Pelvic shape was characterized by the pelvic
incidence angle, which is the sum of sacral slope and pelvic tilt, before and
after the treatment by regular onabotulinumtoxinA injections into the hip
flexors, and the use of soft lumbar brace over 5 years. RESULTS: The sagittal
balance of the spine was improved following the treatment, with a reduction in
lumbar lordosis and sacral slope. The reduction in lumbar hyperextension likely
reduced the risk of spondylolysis, low back pain, and degenerative
spondylolisthesis in adulthood. CONCLUSION: A biomechanical approach to the
evaluation of the pelvic-spinal complex offers new perspectives to increase the
understanding of spinal balance in children with cerebral palsy, providing more
options for treatment, such as onabotulinumtoxinA.
PMID- 28503622
TI - Stiff-Person Syndrome and Graves' Disease: A Pediatric Case Report.
AB - A 9-year-old female child presented with a history of falls, weight loss, diffuse
leg pain, and progressive gait disorder, following 1 previous event described as
a tonic-clonic seizure. She had increased thyroid volume, brisk symmetric
reflexes, abnormal gait, and painful spasms of the paraspinal musculature.
Thyroid function tests indicated biochemical hyperthyroidism, and thyrotropin
receptor antibodies were positive. Her electromyography showed continuous
activation of normal motor units of the paraspinal and proximal lower extremity
muscles. The patient had a diagnosis of Graves' disease with associated stiff
person syndrome, with elevated anti-glutamic acid decarboxylase antibody levels.
After intravenous immunoglobulin therapy, her ambulation was substantially
improved and the symptoms of stiff-person syndrome decreased dramatically.
PMID- 28503623
TI - Seven-Digit Creatine Kinase in Acute Rhabdomyolysis in a Child.
AB - Rhabdomyolysis is an acute life-threatening condition that can occur in childhood
secondary to many causes. The authors report the case of a 3-year-old male child
who presented with acute rhabdomyolysis. The peak plasma creatine kinase level
was extremely high. The 2 main causes of rhabdomyolysis in childhood are viral
myositis and trauma, which can sometimes lead to acute renal failure. The highest
creatine kinase levels reported in the literature so far was a 6-digit level in
2014 case report. In this study, the authors report the case of a 7-digit
creatine kinase level in a child secondary to viral myositis who did not require
renal dialysis.
PMID- 28503624
TI - Temporary Efficacy of Pyrimethamine in Juvenile-Onset Tay-Sachs Disease Caused by
2 Unreported HEXA Mutations in the Indian Population.
AB - BACKGROUND: Juvenile Tay-Sachs disease is rarer than other forms of Tay-Sachs
disease and is usually seen in children between the age of 2 and 10 years.
Pyrimethamine as a pharmacological chaperone was used to increase beta
hexosaminidase A activity in this patient. PATIENT: We describe a patient with
Tay-Sachs disease from the Indian population, a juvenile case who presented with
developmental regression starting at the age of three, initially with motor
followed by language regression. She is currently incapacitated with severe
behavioral issues. CONCLUSION: This brief communication gives an insight into the
efficacy of pharmacological chaperones. It also describes two unreported
mutations in hexosaminidase A gene from the Indian population. After commencing
Pyrimethamine, though initial benefits with increase in levels corresponded with
briefly halting the motor regression, the observed increase was only transient
and not associated with discernible beneficial neurological or psychiatric
effects.
PMID- 28503625
TI - Maternal Race-Ethnicity, Immigrant Status, Country of Birth, and the Odds of a
Child With Autism.
AB - The risk of autism spectrum disorder varies by maternal race-ethnicity,
immigration status, and birth region. In this retrospective cohort study, Western
Australian state registries and a study population of 134 204 mothers enabled us
to examine the odds of autism spectrum disorder with intellectual disability in
children born from 1994 to 2005 by the aforementioned characteristics. We
adjusted for maternal age, parity, socioeconomic status, and birth year.
Indigenous women were 50% less likely to have a child with autism spectrum
disorder with intellectual disability than Caucasian, nonimmigrant women.
Overall, immigrant women were 40% less likely to have a child with autism
spectrum disorder with intellectual disability than nonimmigrant women. However,
Black women from East Africa had more than 3.5 times the odds of autism spectrum
disorder with intellectual disability in their children than Caucasian
nonimmigrant women. Research is implicated on risk and protective factors for
autism spectrum disorder with intellectual disability in the children of
immigrant women.
PMID- 28503626
TI - The Effect of Noninvasive Positive Pressure Ventilation on Pneumonia
Hospitalizations in Children With Neurological Disease.
AB - The aim of this retrospective single-institution observational study was to
identify whether the frequency of hospitalizations for pneumonia would change
before and after the initiation of noninvasive positive pressure ventilation in
children with neurological conditions. Included patients were 1 to 18 years old
with an underlying neurological disease and had been prescribed nocturnal
noninvasive positive pressure ventilation. The authors excluded patients with a
tracheostomy or those who used noninvasive positive pressure ventilation solely
for obstructive sleep apnea. A total of 14 patients were included in the study,
among whom there was no significant change in the mean number of pneumonias 2
years before versus after the initiation of noninvasive positive pressure
ventilation (mean difference = -0.714, standard deviation = 2.4, P = .312). These
findings suggest that while noninvasive positive pressure ventilation may not
reduce absolute pneumonia frequency, it may have the beneficial value of
preventing an increase in the frequency of pneumonias over time, especially in
children with progressive respiratory compromise.
PMID- 28503627
TI - Two Novel KCNQ2 Mutations in 2 Families With Benign Familial Neonatal
Convulsions.
AB - Benign familial neonatal convulsion is a rare autosomal dominant inherited
epilepsy syndrome characterized by unprovoked seizures in the first few days of
life, normal psychomotor development, and a positive intergenerational family
history of neonatal seizures. Over 90% of the affected individuals have inherited
causal mutations in KCNQ2, which encodes for the potassium voltage-gated channel
subfamily Q, member 2. Mutations in KCNQ2 are also associated with a severe
neonatal encephalopathy phenotype associated with poor seizure control and
neurodevelopmental deficits. The authors report the clinical presentations,
response to medication, and intrafamilial phenotypic variability in 2 families
with benign familial neonatal convulsions, carrying previously unreported
heterozygous missense mutations, c.1066C>G (p.Leu356Val) and c.1721G19 years) cancer patients were recruited from a
Tertiary Care Hospital in Karachi, Pakistan. The data were collected using the
Functional Assessment of Cancer Therapy-General, a QOL questionnaire. Multiple
linear regression was run to determine the effect of predictor variables, with a
mean QOL score. RESULTS: The overall mean score of QOL as 57.37. The domains of
physical and emotional well-being were mainly affected by the chemotherapy
treatment. Variables such as no previous hospitalization and no significant
changes in life events were positively associated with the QOL. On the other
hand, being female, unemployed, chemotherapy side effects (>1 week), impaired
socialization, and discrimination by family/relatives were negatively associated
with the QOL. CONCLUSIONS: The study findings suggested an overall low QOL among
adult cancer patients undergoing chemotherapy treatment. It is recognized as a
stressful treatment, which adversely affects the QOL of cancer patients.
Interventions should focus on both the physical and psychological issues and need
to be addressed to improve the QOL of adult cancer patients.
PMID- 28503648
TI - Significance of Psychological Stress Response and Health-related Quality of Life
in Spouses of Cancer Patients When Given Bad News.
AB - OBJECTIVE: This study illuminates the degree of psychological stress response
experienced by spouses of cancer patients when given bad news at three different
times (notification of the name of the disease, notification of recurrence, and
notification of terminality) as well as the factors that influence the response
and the health status of the spouse as measured by health-related quality of life
(QOL). METHODS: A total of 203 individuals (57 men and 146 women) who had
received the three types of news were surveyed using a self-report questionnaire
on psychological stress response, marital satisfaction, and health-related QOL
scales. RESULTS: The degree of the psychological stress response was the highest
for notification of terminality, followed by notification of the name of the
disease, and notification of recurrence. The influencing factors varied depending
on the notification period. Although no significant difference was observed for
health-related QOL among the three notification types, significant differences
were observed for certain items when compared with national standard values.
CONCLUSIONS: When a notification of terminality, which produced the highest
psychological stress response, is given, providing care that considers health
related QOL is necessary not only for patients but also for their spouses.
PMID- 28503649
TI - Reliability and Validity Study of a Tool to Measure Cancer Stigma: Patient
Version.
AB - OBJECTIVE: The aim of this methodological study is to establish the validity and
reliability of the Turkish version of "A Questionnaire for Measuring Attitudes
toward Cancer (Cancer Stigma) - Patient version." METHODS: The sample comprised
oncology patients who had active cancer treatment. The construct validity was
assessed using the confirmatory and exploratory factor analysis. RESULTS: The
mean age of the participants was 54.9+/-12.3 years. In the confirmatory factor
analysis, fit values were determined as comparative fit index = 0.93, goodness of
fit index = 0.91, normed-fit index=0.91, and root mean square error of
approximation RMSEA = 0.09 (P <0.05) (Kaiser-Meyer-Olkin = 0.88, chi2 = 1084.41,
Df = 66, and Barletta's test P <0.000). The first factor was "impossibility of
recovery and experience of social discrimination" and the second factor was
"stereotypes of cancer patients." The two-factor structure accounted for 56.74%
of the variance. The Cronbach's alpha value was determined as 0.88 for the two
factor scale. CONCLUSIONS: "A questionnaire for measuring attitudes toward cancer
(cancer stigma) - Patient version" is a reliable and valid questionnaire to
assess stigmatization of cancer in cancer patients.
PMID- 28503650
TI - Hand-held Fan Airflow Stimulation Relieves Dyspnea in Lung Cancer Patients.
AB - OBJECTIVE: The main symptom of lung cancer is dyspnea which can lead to
depression, anxiety, limited independent activities, and decreased quality of
life. The purpose of this study was to identify the effect of airflow stimulation
from a hand-held fan as nonpharmacological palliative intervention on dyspnea in
patients with lung cancer. METHODS: This study used open, randomized, controlled,
crossover trial design involved 21 participants. Diaphragmatic breathing
technique was used in control arm. RESULTS: Wilcoxon test result showed that
airflow stimulation significantly influenced dyspnea scale (P = 0.003) and
respiratory rate (RR) (P = 0.008). Combination of airflow stimulation and
diaphragmatic breathing can lower both dyspnea scale and RR significantly (P <
0.0001). CONCLUSIONS: This combination can be applied on nonhypoxemic dyspneic
lung cancer patients.
PMID- 28503651
TI - Effect of Play-based Occupational Therapy on Symptoms of Hospitalized Children
with Cancer: A Single-subject Study.
AB - OBJECTIVE: Cancer is one of the four leading causes of death in children. Its
courses of diagnosis and treatment can cause physiologic symptoms and
psychological distress that secondarily affect children's quality of life and
participation in daily activities. The aim of this study was to investigate the
effect of play-based occupational therapy on pain, anxiety, and fatigue in
hospitalized children with cancer who were receiving chemotherapy. METHODS: Two
hospitalized children with acute lymphoblastic leukemia at least 4 months after
diagnoses who received two courses of chemotherapy participated in this pilot
study. Takata Play History and Iranian Children Participation Assessment Scale
were used to develop intervention protocol. Nine, 30-45 min play-based
occupational therapy sessions took place for each child. Children filled out the
Faces Pain Scale, Visual Fatigue Scale, and Faces Anxiety Scale before and after
each intervention session. RESULTS: Pain, anxiety, and fatigue levels decreased
in both participants. Furthermore, the results showed a relationship between
pain, anxiety, and fatigue variables in these children. CONCLUSIONS: Play-based
occupational therapy can be effective in improving pain, anxiety, and fatigue
levels in hospitalized children with cancer receiving chemotherapy.
PMID- 28503653
TI - Editorial overview: Neuroscience of education.
PMID- 28503652
TI - Experiences of Caregivers with Spouses Receiving Chemotherapy for Colorectal
Cancer and their Expectations from Nursing Services.
AB - OBJECTIVE: The purpose of this study was to reveal experiences of caregivers
whose spouses were receiving chemotherapy for colorectal cancer and their
expectations from nursing services. METHODS: This is a qualitative study. The
caregivers were interviewed at their home. Sampling criteria were volunteering to
participate in the study, being able to understand Turkish, not having speech or
hearing problems and offering care to spouses with primary colorectal cancer. The
interviews continued until concepts likely to be responses to research questions
repeatedly appeared. Fourteen caregivers with spouses receiving chemotherapy for
colorectal cancer comprised the study sample. Data were collected with a
descriptive characteristics form and a semi-structured interview at in-depth
interviews after making appointments with the caregivers on the phone. The steps
followed in the content analysis were coding data, an organization of codes and
themes, description of findings and evaluation of findings. RESULTS: Experiences
of the caregivers whose spouses were receiving chemotherapy for colorectal cancer
and their expectations from nursing services were found to comprise the following
themes "Facing the Disease," "Difficulties Encountered," "Continuing to Live,"
and "Provision of Health Care Services." CONCLUSIONS: The results of the study
revealed that cancer and its treatment affected not only cancer patients but also
their spouses offering care. Nurses giving care at oncology clinics, public
health centers, and home can make care plans based on the four themes emerging in
this study and can detect problems earlier and create appropriate solutions to
them. They will contribute to the literature revealing needs of people offering
care to oncology patients as well.
PMID- 28503654
TI - Protective Processes Underlying the Links between Marital Quality and Physical
Health.
AB - Although the links between marital quality and physical health are now well
established, the psychological processes through which marriage impacts health
remain unclear. Additionally, prior research on the links between marriage and
health has focused mainly on how negative aspects of relationships (e.g.,
conflict, hostility) can be damaging to one's physical health. In this article,
we describe the strength and strain model of marital quality and health, which
provides a roadmap for studying protective factors underlying marriage-health
links. We home in one relationship process-partner responsiveness-and one broad
class of psychological mechanisms-affective processes-to illustrate core aspects
of the model. Our review suggests that future research will profit from a greater
integration of theory from the social psychology of close relationships into
studies of relationships and health.
PMID- 28503655
TI - Parenting and SES: relative values or enduring principles?
AB - The quality of parenting is a complex and multiply determined construct that is
strongly influenced by the larger ecological context in which it evolves. A
substantial body of literature has documented associations between socioeconomic
status (SES) and parenting but has been limited in its consideration of factors
that may explain or moderate the nature of this relation. The socioeconomic
conditions within which a family lives may powerfully influence parenting through
its effects on parental mental health and via differential access to resources.
Parents' childrearing knowledge and cultural values may also vary along a
socioeconomic gradient, with downstream effects on parenting. Further, both
socioeconomic factors and parenting can independently shape children's health and
development. A more comprehensive understanding of linkages between SES and
parenting may inform preventive intervention efforts to support families from
disadvantaged environments.
PMID- 28503656
TI - Communication Bridge: A pilot feasibility study of Internet-based speech-language
therapy for individuals with progressive aphasia.
AB - INTRODUCTION: Individuals with aphasia symptoms due to neurodegenerative dementia
are under-referred for speech-language therapy (SLT) services. We sought to
determine the feasibility of utilizing telepractice, via Internet video
conferencing, to connect an individual with progressive aphasia due to dementia
to a speech-language pathologist for treatment. METHODS: Participants received an
Initial Evaluation, 8 person-centered Internet-based SLT sessions and two Post
Therapy Evaluations. The feasibility of providing web-based SLT, strategies used
and their compliance, functional gains and the duration of benefit were assessed.
RESULTS: Thirty-four participants from 21 states and Canada were enrolled. Thirty
one participants completed the 6-month Evaluation. Speech-language pathologist
assessed and self-reported functional gains, as well as increased confidence in
communication were documented at 2-months and maintained at 6-months post
enrollment. DISCUSSION: Internet-based SLT using person-centered interventions
provides a feasible model for delivering care to individuals with dementia and
mild/moderate aphasia symptoms who have an engaged care-partner and prior
familiarity with a computer.
PMID- 28503657
TI - An amylin analog used as a challenge test for Alzheimer's disease.
AB - INTRODUCTION: Preclinical studies demonstrate the potential of amylin in the
diagnosis of Alzheimer's disease (AD). We aimed to lay the foundation for
repurposing the amylin analog and a diabetes drug, pramlintide, for AD in humans.
METHODS: We administered a single subcutaneous injection of 60 MUg of pramlintide
to nondiabetic subjects under fasting conditions. RESULTS: None of the
participants developed hypoglycemia after the injection of pramlintide. The
pramlintide challenge induced a significant surge of amyloid-beta peptide and a
decrease in total tau in the plasma of AD subjects but not in control
participants. The pramlintide injection provoked an increase in interleukin 1
receptor antagonist and a decrease in retinol-binding protein 4, which separates
AD subjects from control subjects. DISCUSSION: Pramlintide use appeared to be
safe in the absence of diabetes. The biomarker changes as a result of the
pramlintide challenge, which distinguished AD from control subjects and mild
cognitive impairment.
PMID- 28503658
TI - Emerging Loop-Mediated Isothermal Amplification-Based Microchip and Microdevice
Technologies for Nucleic Acid Detection.
AB - Rapid, sensitive, and selective pathogen detection is of paramount importance in
infectious disease diagnosis and treatment monitoring. Currently available
diagnostic assays based on polymerase chain reaction (PCR) and enzyme-linked
immunosorbent assay (ELISA) are time-consuming, complex, and relatively
expensive, thus limiting their utility in resource-limited settings. Loop
mediated isothermal amplification (LAMP) technique has been used extensively in
the development of rapid and sensitive diagnostic assays for pathogen detection
and nucleic acid analysis and hold great promise for revolutionizing point-of
care molecular diagnostics. Here, we review novel LAMP-based lab-on-a-chip (LOC)
diagnostic assays developed for pathogen detection over the past several years.
We review various LOC platforms based on their design strategies for pathogen
detection and discuss LAMP-based platforms still in development and already in
the commercial pipeline. This review is intended as a guide to the use of LAMP
techniques in LOC platforms for molecular diagnostics and genomic amplifications.
PMID- 28503660
TI - Breast Cancer Downstaging Practices and Breast Health Messaging Preferences Among
a Community Sample of Urban and Rural Ugandan Women.
AB - PURPOSE: Among a community sample of Ugandan women, we provide information about
breast cancer downstaging practices (breast self-examination, clinical breast
examination [CBE]) and breast health messaging preferences across
sociodemographic, health care access, and prior breast cancer exposure factors.
METHODS: Convenience-based sampling was conducted to recruit Ugandan women age 25
years and older to assess breast cancer downstaging practices as well as breast
health messaging preferences to present early for a CBE in the theoretical
scenario of self-detection of a palpable lump (breast health messaging
preferences). RESULTS: The 401 Ugandan women who participated in this survey were
mostly poor with less than a primary school education. Of these women, 27% had
engaged in breast self-examination, and 15% had undergone a CBE. Greater breast
cancer downstaging practices were associated with an urban location, higher
education, having a health center as a regular source of care, and receiving
breast cancer education (P < .05). Women indicated a greater breast health
messaging preference from their provider (66%). This preference was associated
with a rural location, having a health center as a regular source of care, and
receiving breast cancer education (P < .05). CONCLUSION: Most Ugandan women do
not participate in breast cancer downstaging practices despite receipt of breast
cancer education. However, such education increases downstaging practices and
preference for messaging from their providers. Therefore, efforts to downstage
breast cancer in Uganda should simultaneously raise awareness in providers and
support improved education efforts in the community.
PMID- 28503659
TI - Structure and function of histone acetyltransferase MOF.
AB - MOF was first identified in Drosophila melanogaster as an important component of
the dosage compensation complex. As a member of MYST family of histone
acetyltransferase, MOF specifically deposits the acetyl groups to histone H4
lysine 16. Throughout evolution, MOF and its mammalian ortholog have retained
highly conserved substrate specificity and similar enzymatic activities. MOF
plays important roles in dosage compensation, ESC self-renewal, DNA damage and
repair, cell survival, and gene expression regulation. Dysregulation of MOF has
been implicated in tumor formation and progression of many types of human
cancers. This review will discuss the structure and activity of mammalian hMOF as
well as its function in H4K16 acetylation, DNA damage response, stem cell
pluripotency, and carcinogenesis.
PMID- 28503662
TI - Picoliter-volume inkjet printing into planar microdevice reservoirs for low
waste, high-capacity drug loading.
AB - Oral delivery of therapeutics is the preferred route for systemic drug
administration due to ease of access and improved patient compliance. However,
many therapeutics suffer from low oral bioavailability due to low pH and
enzymatic conditions, poor cellular permeability, and low residence time.
Microfabrication techniques have been used to create planar, asymmetric
microdevices for oral drug delivery to address these limitations. The geometry of
these microdevices facilitates prolonged drug exposure with unidirectional
release of drug toward gastrointestinal epithelium. While these devices have
significantly enhanced drug permeability in vitro and in vivo, loading drug into
the micron-scale reservoirs of the devices in a low-waste, high-capacity manner
remains challenging. Here, we use picoliter-volume inkjet printing to load
topotecan and insulin into planar microdevices efficiently. Following a simple
surface functionalization step, drug solution can be spotted into the microdevice
reservoir. We show that relatively high capacities of both topotecan and insulin
can be loaded into microdevices in a rapid, automated process with little to no
drug waste.
PMID- 28503663
TI - The Communication Play Protocol: Capturing Variations in Language Development.
AB - The Communication Play Protocol (CPP) is a semi-naturalistic, lab-based
observational procedure that showcases parent-child interactions. This article
reflects on how the CPP has matured since we described it over 25 years ago in
the May 1999 issue of Perspectives. We emphasize how the CPP has provided us with
a stable frame to observe both typically developing children and children with
developmental challenges including autism spectrum disorder as they communicate
with caregivers in a range of contexts. We also describe three versions of the
CPP that have been designed to address different research questions and several
methods including engagement state coding and rating items that have been used to
extract data from video records of the CPP. We conclude that the CPP can provide
both researchers and clinicians with a valuable way to systematically capture
variations in language development.
PMID- 28503661
TI - In vitro Detection of Hypoxia using a Ratiometric Quantum Dot-based Oxygen
Sensor.
AB - A quantum-dot based ratiometric fluorescent oxygen probe for the detection of
hypoxia in live cells is reported. The system is comprised of a water-soluble
near-infrared emissive quantum dot conjugated to perylene dye. The response to
the oxygen concentration is investigated using enzymatic oxygen scavenging in
water, while in vitro studies were performed with HeLa cells incubated under
varying O2 levels. In both cases a significant enhancement in dye/QD emission
intensity ratio was observed in the deoxygenated environment, demonstrating the
possible use of this probe for cancer research.
PMID- 28503665
TI - Probabilistic modeling of bifurcations in single-cell gene expression data using
a Bayesian mixture of factor analyzers.
AB - Modeling bifurcations in single-cell transcriptomics data has become an
increasingly popular field of research. Several methods have been proposed to
infer bifurcation structure from such data, but all rely on heuristic non
probabilistic inference. Here we propose the first generative, fully
probabilistic model for such inference based on a Bayesian hierarchical mixture
of factor analyzers. Our model exhibits competitive performance on large datasets
despite implementing full Markov-Chain Monte Carlo sampling, and its unique
hierarchical prior structure enables automatic determination of genes driving the
bifurcation process. We additionally propose an Empirical-Bayes like extension
that deals with the high levels of zero-inflation in single-cell RNA-seq data and
quantify when such models are useful. We apply or model to both real and
simulated single-cell gene expression data and compare the results to existing
pseudotime methods. Finally, we discuss both the merits and weaknesses of such a
unified, probabilistic approach in the context practical bioinformatics analyses.
PMID- 28503664
TI - Fixing the stimulus-as-fixed-effect fallacy in task fMRI.
AB - Most functional magnetic resonance imaging (fMRI) experiments record the brain's
responses to samples of stimulus materials (e.g., faces or words). Yet the
statistical modeling approaches used in fMRI research universally fail to model
stimulus variability in a manner that affords population generalization, meaning
that researchers' conclusions technically apply only to the precise stimuli used
in each study, and cannot be generalized to new stimuli. A direct consequence of
this stimulus-as-fixed-effect fallacy is that the majority of published fMRI
studies have likely overstated the strength of the statistical evidence they
report. Here we develop a Bayesian mixed model (the random stimulus model; RSM)
that addresses this problem, and apply it to a range of fMRI datasets. Results
demonstrate considerable inflation (50-200% in most of the studied datasets) of
test statistics obtained from standard "summary statistics"-based approaches
relative to the corresponding RSM models. We demonstrate how RSMs can be used to
improve parameter estimates, properly control false positive rates, and test
novel research hypotheses about stimulus-level variability in human brain
responses.
PMID- 28503666
TI - Robust long-read native DNA sequencing using the ONT CsgG Nanopore system.
AB - Background: The ability to obtain long read lengths during DNA sequencing has
several potentially important practical applications. Especially long read
lengths have been reported using the Nanopore sequencing method, currently
commercially available from Oxford Nanopore Technologies (ONT). However, early
reports have demonstrated only limited levels of combined throughput and sequence
accuracy. Recently, ONT released a new CsgG pore sequencing system as well as a
250b/s translocation chemistry with potential for improvements. Methods: We made
use of such components on ONTs miniature 'MinION' device and sequenced native
genomic DNA obtained from the near haploid cancer cell line HAP1. Analysis of our
data was performed utilising recently described computational tools tailored for
nanopore/long-read sequencing outputs, and here we present our key findings.
Results: From a single sequencing run, we obtained ~240,000 high-quality mapped
reads, comprising a total of ~2.3 billion bases. A mean read length of 9.6kb and
an N50 of ~17kb was achieved, while sequences mapped to reference with a mean
identity of 85%. Notably, we obtained ~68X coverage of the mitochondrial genome
and were able to achieve a mean consensus identity of 99.8% for sequenced mtDNA
reads. Conclusions: With improved sequencing chemistries already released and
higher-throughput instruments in the pipeline, this early study suggests that ONT
CsgG-based sequencing may be a useful option for potential practical long-read
applications.
PMID- 28503667
TI - Neopeptide Analyser: A software tool for neopeptide discovery in proteomics data.
AB - Experiments involving mass spectrometry (MS)-based proteomics are widely used for
analyses of connective tissues. Common examples include the use of relative
quantification to identify differentially expressed peptides and proteins in
cartilage and tendon. We are working on characterising so-called 'neopeptides',
i.e. peptides formed due to native cleavage of proteins, for example under
pathological conditions. Unlike peptides typically quantified in MS workflows due
to the in vitro use of an enzyme such as trypsin, a neopeptide has at least one
terminus that was not due to the use of trypsin in the workflow. The
identification of neopeptides within these datasets is important in understanding
disease pathology, and the development of antibodies that could be utilised as
diagnostic biomarkers for diseases, such as osteoarthritis, and targets for novel
treatments. Our previously described neopeptide data analysis workflow was
laborious and was not amenable to robust statistical analysis, which reduced
confidence in the neopeptides identified. To overcome this, we developed
'Neopeptide Analyser', a user friendly neopeptide analysis tool used in
conjunction with label-free MS quantification tool Progenesis QIP for proteomics.
Neopeptide Analyser filters data sourced from Progenesis QIP output to identify
neopeptide sequences, as well as give the residues that are adjacent to the
peptide in its corresponding protein sequence. It also produces normalised values
for the neopeptide quantification values and uses these to perform statistical
tests, which are also included in the output. Neopeptide Analyser is available as
a Java application for Mac, Windows and Linux. The analysis features and ease of
use encourages data exploration, which could aid the discovery of novel pathways
in extracellular matrix degradation, the identification of potential biomarkers
and as a tool to investigate matrix turnover. Neopeptide Analyser is available
from https://github.com/PGB-LIV/neo-pep-tool/releases/.
PMID- 28503668
TI - David Stafford-Clark (1916-1999): Seeing through a celebrity psychiatrist.
AB - This article uses the mass-media career of the British psychiatrist David
Stafford-Clark (1916-1999) as a case study in the exercise of cultural authority
by celebrity medical professionals in post-war Britain. Stafford-Clark rose to
prominence in the mass media, particularly through his presenting work on medical
and related topics for BBC TV and Radio, and was in the vanguard of psychiatrists
and physicians who eroded professional edicts on anonymity. At the height of his
career, he traded upon his celebrity status, and consequent cultural authority,
to deliver mass media sermons on a variety of social, cultural, and political
topics. Stafford-Clark tried to preserve his sense of personal and intellectual
integrity by clinging to a belief that his authority in the public sphere was
ultimately to be vindicated by his literary, intellectual, and spiritual
significance. But as his credibility dwindled, he came to distrust the cultural
intermediaries, such as broadcasters and publishers, who had supported him.
PMID- 28503669
TI - Dietary diversity and child malnutrition in Ghana.
AB - The health of children in Ghana has improved in recent years. However, the
current prevalence rates of malnutrition remain above internationally acceptable
levels. This study, therefore, revisits the determinants of child health by using
Ghana's Multiple Indicator Cluster Survey to investigate the effect of infant
feeding practices on child health. We used the World Health Organization's Infant
and Young Children Feeding guidelines to measure dietary quality. The econometric
analyses show that dietary diversity may cause improvement in children's health
in Ghana. This suggests that educational campaigns on proper infant feeding and
complementary dieting could be an effective means of improving the health of
children in Ghana.
PMID- 28503672
TI - Quantum fluctuations beyond the Gutzwiller approximation.
AB - We present a simple scheme to evaluate linear response functions including
quantum fluctuation corrections on top of the Gutzwiller approximation. The
method is derived for a generic multiband lattice Hamiltonian without any
assumption about the dynamics of the variational correlation parameters that
define the Gutzwiller wavefunction, and which thus behave as genuine dynamical
degrees of freedom that add on those of the variational uncorrelated Slater
determinant. We apply the method to the standard half-filled single-band Hubbard
model. We are able to recover known results, but, as by-product, we also obtain
few novel ones. In particular, we show that quantum fluctuations can reproduce
almost quantitatively the behaviour of the uniform magnetic susceptibility
uncovered by dynamical mean field theory, which, though enhanced by correlations,
is found to be smooth across the paramagnetic Mott transition. By contrast, the
simple Gutzwiller approximation predicts that susceptibility to diverge at the
transition.
PMID- 28503670
TI - Encoding of contextual fear memory requires de novo proteins in the prelimbic
cortex.
AB - BACKGROUND: Despite our understanding of the significance of the prefrontal
cortex in the consolidation of long-term memories (LTM), its role in the encoding
of LTM remains elusive. Here we investigated the role of new protein synthesis in
the mouse medial prefrontal cortex (mPFC) in encoding contextual fear memory.
METHODS: Because a change in the association of mRNAs to polyribosomes is an
indicator of new protein synthesis, we assessed the changes in polyribosome
associated mRNAs in the mPFC following contextual fear conditioning (CFC) in the
mouse. Differential gene expression in mPFC was identified by polyribosome
profiling (n = 18). The role of new protein synthesis in mPFC was determined by
focal inhibition of protein synthesis (n = 131) and by intra-prelimbic cortex
manipulation (n = 56) of Homer 3, a candidate identified from polyribosome
profiling. RESULTS: We identified several mRNAs that are differentially and
temporally recruited to polyribosomes in the mPFC following CFC. Inhibition of
protein synthesis in the prelimbic (PL), but not in the anterior cingulate cortex
(ACC) region of the mPFC immediately after CFC disrupted encoding of contextual
fear memory. Intriguingly, inhibition of new protein synthesis in the PL 6 hours
after CFC did not impair encoding. Furthermore, expression of Homer 3, an mRNA
enriched in polyribosomes following CFC, in the PL constrained encoding of
contextual fear memory. CONCLUSIONS: Our studies identify several molecular
substrates of new protein synthesis in the mPFC and establish that encoding of
contextual fear memories require new protein synthesis in PL subregion of mPFC.
PMID- 28503671
TI - HIV/HCV Co-infection, Liver Disease Progression, and Age-Related IGF-1 Decline.
AB - BACKGROUND: We have previously reported that persons co-infected with HIV and
hepatitis C virus (HCV) had liver disease stages similar to HIV-uninfected
individuals who were approximately 10 years older. Insulin-like growth factor
1(IGF-1) levels have long been known to decline with advancing age in humans and
non-humans alike. We examined whether HIV infection affects the expected decline
in IGF-1 in persons with chronic hepatitis C virus (HCV) infection and if that
alteration in IGF-1 decline contributes to the link between HIV, aging, and liver
disease progression. METHODS: A total of 553 individuals with HCV infection were
studied from the AIDS Linked to the Intravenous Experience (ALIVE) cohort for
whom more than 10 years of follow-up was available. Serum IGF-1 levels were
determined by ELISA and evaluated according to baseline characteristics and over
time by HIV status and liver disease progression. Linear regression with
generalized estimating equations was used to determine whether IGF-1 decline over
time was independently associated with liver disease progression. RESULTS:
Baseline IGF-1 levels were strongly associated with age (P < 0.0001) but not with
gender or HIV infection. Levels of IGF-1 declined at a rate of -1.75 ng/mL each
year in HCV mono-infected individuals and at a rate of -1.23 ng/mL each year in
HIV/HCV co-infected individuals (P < 0.05). In a multivariable linear regression
model, progression of liver fibrosis was associated with HIV infection and age,
as well as with a slower rate of IGF-1 decline (P = 0.001); however, the rate of
IGF-1 decline did not alter the strength of the associations between HIV, liver
disease, and age. CONCLUSIONS: The normal decline in IGF-1 levels with age was
attenuated in HIV/HCV co-infected individuals compared to those with HCV mono
infection, and slower IGF-1 decline was independently associated with liver
disease progression.
PMID- 28503673
TI - Non-Fermi-liquid behavior in quantum impurity models with superconducting
channels.
AB - We study how the non-Fermi-liquid nature of the overscreened multi-channel Kondo
impurity model affects the response to a BCS pairing term that, in the absence of
the impurity, opens a gap Delta. We find that the low-energy spectrum in the
limit Delta -> 0 actually does not correspond to the spectrum strictly at Delta =
0. In particular, in the two-channel Kondo model the Delta -> 0 ground state is
an orbitally degenerate spin-singlet, while it is an orbital singlet with a
residual spin degeneracy at Delta = 0. In addition, there are fractionalized spin
1/2 sub-gap excitations whose energy in units of Delta tends towards a finite and
universal value when Delta -> 0; as if the universality of the anomalous power
law exponents that characterise the overscreened Kondo effect turned into
universal energy ratios when the scale invariance is broken by Delta ? 0. This
intriguing phenomenon can be explained by the renormalisation flow towards the
overscreened fixed point and the gap cutting off the orthogonality catastrophe
singularities. We also find other non-Fermi liquid features at finite Delta: the
local density of states lacks coherence peaks, the states in the continuum above
the gap are unconventional, and the boundary entropy is a non-monotonic function
of temperature. The persistent sub-gap excitations are characteristic of the non
Fermi-liquid fixed-point of the model, and thus depend on the impurity spin and
the number of screening channels.
PMID- 28503674
TI - Identifying brain nociceptive information transmission in patients with chronic
somatic pain.
AB - INTRODUCTION: Recent advances regarding mechanisms of chronic pain emphasize the
role of corticolimbic circuitry in predicting risk for chronic pain,
independently from site of injury-related parameters. These results compel
revisiting the role of peripheral nociceptive signaling in chronic pain. We
address this issue by examining what brain circuitry transmit information
regarding the intensity of chronic pain and how this information may be related
to a common co-morbidity, depression. METHODS: Resting state functional MRI was
used in a large group of chronic pain patients (n=40 chronic back pain, CBP, and
n=44 osteoarthritis, OA patients), and in comparison to healthy subjects (n=88).
We used a graph theoretical measure, degree count, to investigate voxel-wise
information sharing/transmission in the brain. Degree count, a functional
connectivity based measure, identifies the number of voxels functionally
connected to every given voxel. Subdividing the chronic pain cohort into
discovery, replication, and also for overall group we show that only degree
counts of diencephalic voxels centered in the ventral lateral thalamus reflected
intensity of chronic pain, independently of depression. RESULTS: Pain intensity
was reliably associated with degree count of the thalamus, which was correlated
negatively with components of the default mode network and positively with the
periaqueductal grey (in contrast to healthy controls). Depression scores were not
reliably associated with regional degree count. CONCLUSION: Collectively the
results suggest that, across two types of chronic pain, nociceptive specific
information is relayed through the spinothalamic pathway to the lateral thalamus,
potentiated by pro-nociceptive descending modulation, and interrupting cortical
cognitive processes.
PMID- 28503675
TI - Costs of a Staff Communication Intervention to Reduce Dementia Behaviors in
Nursing Home Care.
AB - CONTEXT: Persons with Alzheimer's disease and other dementias experience
behavioral symptoms that frequently result in nursing home (NH) placement.
Managing behavioral symptoms in the NH increases staff time required to complete
care, and adds to staff stress and turnover, with estimated cost increases of
30%. The Changing Talk to Reduce Resistivenes to Dementia Care (CHAT) study found
that an intervention that improved staff communication by reducing elderspeak led
to reduced behavioral symptoms of dementia or resistiveness to care (RTC).
OBJECTIVE: This analysis evaluates the cost-effectiveness of the CHAT
intervention to reduce elderspeak communication by staff and RTC behaviors of NH
residents with dementia. DESIGN: Costs to provide the intervention were
determined in eleven NHs that participated in the CHAT study during 2011-2013
using process-based costing. Each NH provided data on staff wages for the quarter
before and for two quarters after the CHAT intervention. An incremental cost
effectiveness analysis was completed. ANALYSIS: An average cost per participant
was calculated based on the number and type of staff attending the CHAT training,
plus materials and interventionist time. Regression estimates from the parent
study then were applied to determine costs per unit reduction in staff elderspeak
communication and resident RTC. RESULTS: A one percentage point reduction in
elderspeak costs $6.75 per staff member with average baseline elderspeak usage.
Assuming that each staff cares for 2 residents with RTC, a one percentage point
reduction in RTC costs $4.31 per resident using average baseline RTC.
CONCLUSIONS: Costs to reduce elderspeak and RTC depend on baseline levels of
elderspeak and RTC, as well as the number of staff participating in CHAT training
and numbers of residents with dementia-related behaviors. Overall, the 3-session
CHAT training program is a cost-effective intervention for reducing RTC behaviors
in dementia care.
PMID- 28503676
TI - Learning Optimal Individualized Treatment Rules from Electronic Health Record
Data.
AB - Medical research is experiencing a paradigm shift from "one-size-fits-all"
strategy to a precision medicine approach where the right therapy, for the right
patient, and at the right time, will be prescribed. We propose a statistical
method to estimate the optimal individualized treatment rules (ITRs) that are
tailored according to subject-specific features using electronic health records
(EHR) data. Our approach merges statistical modeling and medical domain knowledge
with machine learning algorithms to assist personalized medical decision making
using EHR. We transform the estimation of optimal ITR into a classification
problem and account for the non-experimental features of the EHR data and
confounding by clinical indication. We create a broad range of feature variables
that reflect both patient health status and healthcare data collection process.
Using EHR data collected at Columbia University clinical data warehouse, we
construct a decision tree for choosing the best second line therapy for treating
type 2 diabetes patients.
PMID- 28503677
TI - Annotating Logical Forms for EHR Questions.
AB - This paper discusses the creation of a semantically annotated corpus of questions
about patient data in electronic health records (EHRs). The goal is to provide
the training data necessary for semantic parsers to automatically convert EHR
questions into a structured query. A layered annotation strategy is used which
mirrors a typical natural language processing (NLP) pipeline. First, questions
are syntactically analyzed to identify multi-part questions. Second, medical
concepts are recognized and normalized to a clinical ontology. Finally, logical
forms are created using a lambda calculus representation. We use a corpus of 446
questions asking for patient-specific information. From these, 468 specific
questions are found containing 259 unique medical concepts and requiring 53
unique predicates to represent the logical forms. We further present detailed
characteristics of the corpus, including inter-annotator agreement results, and
describe the challenges automatic NLP systems will face on this task.
PMID- 28503678
TI - Beyond Abandonment to Next Steps: Understanding and Designing for Life after
Personal Informatics Tool Use.
AB - Recent research examines how and why people abandon self-tracking tools. We
extend this work with new insights drawn from people reflecting on their
experiences after they stop tracking, examining how designs continue to influence
people even after abandonment. We further contrast prior work considering
abandonment of health and wellness tracking tools with an exploration of why
people abandon financial and location tracking tools, and we connect our findings
to models of personal informatics. Surveying 193 people and interviewing 12
people, we identify six reasons why people stop tracking and five perspectives on
life after tracking. We discuss these results and opportunities for design to
consider life after self-tracking.
PMID- 28503680
TI - Editorial: The dawn of adhesive dentistry.
PMID- 28503679
TI - Crumbs: Lightweight Daily Food Challenges to Promote Engagement and Mindfulness.
AB - Many people struggle with efforts to make healthy behavior changes, such as
healthy eating. Several existing approaches promote healthy eating, but present
high barriers and yield limited engagement. As a lightweight alternative approach
to promoting mindful eating, we introduce and examine crumbs: daily food
challenges completed by consuming one food that meets the challenge. We examine
crumbs through developing and deploying the iPhone application Food4Thought. In a
3-week field study with 61 participants, crumbs supported engagement and
mindfulness while offering opportunities to learn about food. Our 2*2 study
compared nutrition versus non-nutrition crumbs coupled with social versus non
social features. Nutrition crumbs often felt more purposeful to participants, but
non-nutrition crumbs increased mindfulness more than nutrition crumbs. Social
features helped sustain engagement and were important for engagement with non
nutrition crumbs. Social features also enabled learning about the variety of
foods other people use to meet a challenge.
PMID- 28503682
TI - Hydroboration of alkynes and nitriles using an alpha-diimine cobalt hydride
catalyst.
AB - Addition of NaEt3BH to (Ph2PPrDI)CoCl2 affords the corresponding monohydride,
(Ph2PPrDI)CoH. X-ray diffraction and DFT calculations indicate that this compound
possesses a radical monoanion alpha-DI chelate and a Co(ii) centre. Notably,
(Ph2PPrDI)CoH catalyzes the hydroboration of alkynes and dihydroboration of
nitriles under mild conditions.
PMID- 28503684
TI - Phase transformations, anisotropic pyroelectric energy harvesting and
electrocaloric properties of (Pb,La)(Zr,Sn,Ti)O3 single crystals.
AB - (Pb,La)(Zr,Sn,Ti)O3 (PLZST) single crystals with their chemical composition
located at the tetragonal antiferroelectric region are grown via the flux method
in a PbO-PbF2-B2O3 mixture. Segregation of the Ti4+ component in the as-grown
crystals is observed due to the strong affinity between the oxygen anion and Ti4+
ions. The critical electric field of the antiferroelectric to ferroelectric phase
transition is determined to be about 0.5 kV mm-1. The electric field induced
ferroelectric phase transforms back into the antiferroelectric phase at a
depolarization temperature of 125 degrees C. Anisotropy of the harvested energy
density and electrocaloric behaviors are achieved for the [100], [110] and [111]
oriented PLZST crystals. Based on the thermodynamic theory approach, all the
abovementioned behaviors originate from the anisotropic total entropy change.
Enhanced electrocaloric strength (0.3 K mm kV-1) and the harvested energy density
of 0.62 J cm-3 are obtained in the [111]-oriented PLZST crystals. Our results
demonstrate the competence of PLZST single crystals for cooling devices and
pyroelectric energy harvesting and provide new opportunities to improve energy
harvesting density and electrocaloric properties via the anisotropic structural
layout, which make the PLZST crystals attractive for solid state cooling devices
and energy conversion technologies.
PMID- 28503683
TI - Cellular evaluation of diselenonicotinamide (DSNA) as a radioprotector against
cell death and DNA damage.
AB - Diselenonicotinamide (DSNA), a synthetic organoselenium compound, was evaluated
for its radioprotective effect in cellular models. A clonogenic assay in Chinese
Hamster Ovary (CHO) cells and an apoptosis assay in murine splenic lymphocytes
indicated that pre-treatment with DSNA at a concentration of 25 MUM significantly
protected them from radiation-induced cell death. Upon irradiation (1-12 Gy),
dose-response studies were carried out under similar treatment conditions, and
its dose modification factor (DMF) was estimated to be 1.26. Furthermore, DSNA
showed its radioprotective effect, even when administered after exposure to
radiation. Mechanistic investigation revealed that DSNA increased the
intracellular levels of GPx and GSH in irradiated cells. In line with this
observation, the addition of a pharmacological inhibitor of GPx cycle, abrogated
the activity of DSNA. The radioprotective effect of DSNA was also complemented by
its ability to prevent radiation-induced DNA damage as monitored by micronucleus
and gamma-H2AX assays. Furthermore, treatment with DSNA did not show much change
in the expressions of Nrf2 dependent genes (gamma-GCL and HO-1), but the presence
of a pharmacological inhibitor of Nrf2 abrogated the radioprotective activity of
DSNA against cell death and DNA damage. Additionally, ATRA treatment also
inhibited the DSNA-mediated up-regulation of a repair gene RAD51, suggesting
possible involvement of basal Nrf2 in the anti-genotoxic effect of DSNA. In
conclusion, the present study demonstrates radioprotection by a synthetic
organoselenium compound containing nutritionally important moieties like selenium
and nicotinamide.
PMID- 28503685
TI - Intracellular-molecular changes in plasma-irradiated budding yeast cells studied
using multiplex coherent anti-Stokes Raman scattering microscopy.
AB - Interactions between non-equilibrium atmospheric-pressure plasma (NEAPP) and
living cells were examined using multiplex coherent anti-Stokes Raman scattering
(CARS) microscopy. Our multiplex CARS analyses revealed that NEAPP irradiation
generates short-lived radicals that induce a decrease in the mitochondrial
activity of budding yeast cells.
PMID- 28503686
TI - Mesoporous nanocarriers with a stimulus-responsive cyclodextrin gatekeeper for
targeting tumor hypoxia.
AB - Tissue hypoxia developed in most malignant tumors makes a significant difference
to normal tissues in the reduction potential and the activity of various
bioreductive enzymes. Given the superior enzymatic activity of NAD(P)H:quinone
oxidoreductase 1 (NQO1, a cytosolic reductase up-regulated in many human cancers)
in hypoxia relative to that in normoxia, NQO1 has great potential for targeting
hypoxic tumor cells. In the present report, the core concept of hypoxic NQO1
responsive mesoporous silica nanoparticles (MSNs) is based on the reasoning that
the superior enzymatic activity of NQO1 within hypoxic cancer cells can be
utilized as a key stimulus for the selective cleavage of an azobenzene stalk
triggering the on-off gatekeeping for controlled release of guest drugs. We
corroborate that the NQO1 specifically triggers to release the entrapped drug in
the nanochannel of MSNs by reductive cleavage of the azobenzene linker only under
hypoxic conditions in a controlled manner not only in vitro but also in vivo.
Therefore, our results indicate that Si-Azo-CD-PEG could be utilized as a hypoxic
cancer-targeting drug delivery carrier, and further suggest that the azobenzene
linker could generally be useful for the construction of hypoxic NQO1-responsive
nanomaterials.
PMID- 28503687
TI - Adapting BODIPYs to singlet oxygen production on silica nanoparticles.
AB - A modified Stober method is used to synthesize spherical core-shell silica
nanoparticles (NPs) with an external surface functionalized by amino groups and
with an average size around 50 nm. Fluorescent dyes and photosensitizers of
singlet oxygen were fixed, either separately or conjointly, respectively in the
core or in the shell. Rhodamines were encapsulated in the core with relatively
high fluorescence quantum yields (Phifl >= 0.3), allowing fluorescence tracking
of the particles. Various photosensitizers of singlet oxygen (PS) were covalenty
coupled to the shell, allowing singlet oxygen production. The stability of NP
suspensions strongly deteriorated upon grafting the PS, affecting their apparent
singlet oxygen quantum yields. Agglomeration of NPs depends both on the type and
on the amount of grafted photosensitizer. New, lab-made, halogenated 4,4-difluoro
4-bora-3a,4a-diaza-s-indacenes (BODIPY) grafted to the NPs achieved higher
singlet oxygen quantum yields (PhiDelta ~ 0.35-0.40) than Rose Bengal (RB)
grafted NPs (PhiDelta ~ 0.10-0.27). Finally, we combined both fluorescence and PS
functions in the same NP, namely a rhodamine in the silica core and a BODIPY or
RB grafted in the shell, achieving the performance Phifl ~ 0.10-0.20, PhiDelta ~
0.16-0.25 with a single excitation wavelength. Thus, proper choice of the dyes,
of their concentrations inside and on the NPs and the grafting method enables
fine-tuning of singlet oxygen production and fluorescence emission.
PMID- 28503688
TI - Intermolecular cascade annulations of N-(arylsulfonyl)acrylamides with dual
C(sp3)-H bonds: divergent access to indanes and pyrrolidin-2-ones.
AB - A new divergent intermolecular cascade annulation reaction of N
(arylsulfonyl)acrylamides with dual alkyl C(sp3)-H bonds for producing two types
of five-membered rings, indanes and pyrrolidin-2-ones, is described. By using
cycloalkanes and common alkanes as a one-carbon unit, an intermolecular [4+1]
cascade carboannulation of N-(arylsulfonyl)acrylamides was achieved via a
sequence of three C-H bond functionalization/aryl migration/desulfonylation that
enables the formation of three C-C bonds and one N-H bond. When the one-carbon
unit was changed to cycloalkyl ethers, the alternative intermolecular [4+1]
cascade heteroannulation reaction occurred and allowed the construction of two C
C bonds and one C-N bond through dual C-H bond functionalization, aryl migration
and desulfonylation cascades.
PMID- 28503689
TI - Effects of elemene on inhibiting proliferation of vascular smooth muscle cells
and promoting reendothelialization at the stent implantation site.
AB - Anticancer drugs are commonly used as inhibitors of vascular smooth muscle cell
(VSMC) proliferation in clinical treatments. This study aims to investigate how
elemene affects the proliferation of VSMCs, the restenosis, and the
reendothelialization after implanting the elemene-coated stents. VSMCs derived
from rat aorta were used to test the cell proliferation, cell cycle, migration,
apoptosis, cytoskeletal protein F-actin, intracellular Ca2+, IncRNA chip and gene
expression of PCNA, P53, and Cx43 when cultured with elemene. It was found that
elemene can inhibit proliferation, induce apoptosis and block the connections
between VSMCs in a dose-dependent manner. IncRNA chip analysis has revealed that
there was a significant difference in the expression of 1417 genes and 34
signaling pathways. Elemene liposome membranes prepared by electrostatic spray
could also inhibit the proliferation of VSMCs. In addition, after implanting the
elemene-coated stent into a rabbit iliac artery for 12 weeks, the surface of
elemene-coated stents was fully covered with a layer of neointima and a few
platelets. However, a large number of platelets aggregated and attached on the
uncoated stents (control samples). In conclusion, elemene could inhibit VSMC
proliferation in vitro, which involved the regulation of various signal
transduction pathways, and elemene-coated stents could promote endothelialization
after stent implantation. Thus, elemene has great potential for the clinical
treatment of restenosis and reendothelialization.
PMID- 28503690
TI - Ionic liquid/H2O-mediated synthesis of mesoporous organic polymers and their
application in methylation of amines.
AB - Mesoporous Troger's base-functionalized polymers (Meso-TBPs) were prepared using
a sulfonic acid group functionalized ionic liquid/H2O system, with surface areas
up to 431 m2 g-1 and pore sizes of 3-15 nm. Ir(ii) coordinated Meso-TBPs
exhibited extraordinary catalytic performance in the N-methylation of amines
using methanol.
PMID- 28503691
TI - A rapidly-prototyped microfluidic device for size-based nucleic acid
fractionation using isotachophoresis.
AB - We present a novel microfluidic device for size-based nucleic acid (NA)
fractionation using isotachophoresis (ITP) and an ionic spacer. Our rapid
prototyped laser-cut plastic device has easily modifiable channel dimensions, can
process up to 10 MUL of sample, and contains an in-line extraction reservoir for
minimally-disruptive manual collection of size-fractionated NAs. We designed
custom buffering reservoirs using 1 mL pipette tips to provide high buffering
capacity and prevent bubbles from entering the microfluidic channels. We
demonstrated the utility of the device by implementing a proof-of-concept assay
in which NAs were preconcentrated (via ITP) and then segregated by size (using
the ionic spacer and sieving matrix) to generate two separate fractions, the
first comprised of small (<50 nt) NA, and the second comprised of NAs of all
sizes. Through this approach, we demonstrated size-based fractionation of both
DNA and RNA samples (a mixture of synthetic ssDNA molecules, and a commercially
available RNA molecular weight standard, respectively). Our results indicate that
this simple, rapid (<=10 min), and label-free approach is a promising and cost
effective alternative to the commercially-available size-selection kits currently
on the market. We discuss the design and features of the device, as well as
challenges which must be met in the future in order to further improve its
performance and utility.
PMID- 28503692
TI - Time-resolved measurements of product formation in the low-temperature (550-675
K) oxidation of neopentane: a probe to investigate chain-branching mechanism.
AB - Product formation, in particular ketohydroperoxide formation and decomposition,
were investigated in time-resolved, Cl-atom initiated neopentane oxidation
experiments in the temperature range 550-675 K using a photoionization time-of
flight mass spectrometer. Ionization light was provided either by Advanced Light
Source tunable synchrotron radiation or ~10.2 eV fixed energy radiation from a H2
discharge lamp. Experiments were performed both at 1-2 atm pressure using a high
pressure reactor and also at ~9 Torr pressure employing a low-pressure reactor
for comparison. Because of the highly symmetric structure of neopentane,
ketohydroperoxide signal can be attributed to a 3-hydroperoxy-2,2
dimethylpropanal isomer, i.e. from a gamma-ketohydroperoxide (gamma-KHP). The
photoionization spectra of the gamma-KHP measured at low- and high pressures and
varying oxygen concentrations agree well with each other, further supporting they
originate from the single isomer. Measurements performed in this work also
suggest that the "Korcek" mechanism may play an important role in the
decomposition of 3-hydroperoxy-2,2-dimethylpropanal, especially at lower
temperatures. However, at higher temperatures where gamma-KHP decomposition to
hydroxyl radical and oxy-radical dominates, oxidation of the oxy-radical yields a
new important channel leading to acetone, carbon monoxide, and OH radical.
Starting from the initial neopentyl + O2 reaction, this channel releases
altogether three OH radicals. A strongly temperature-dependent reaction product
is observed at m/z = 100, likely attributable to 2,2-dimethylpropanedial.
PMID- 28503693
TI - Exploiting the unusual effects of fluorine in methodology.
AB - Fluorination of organic molecules significantly impacts the basic physicochemical
properties of small and large biologically active molecules, agrichemicals, and
materials. Thus, the development of synthetic reactions to access these
substructures is important for many applied fields of chemistry. However, these
fluorine-induced perturbations of chemical properties can inhibit standard
chemical transformations, which provides unique challenges for synthetic organic
chemists. In addition, the physicochemical properties imparted by fluorinated
substituents can enable distinct reactivity patterns relative to non-fluorinated
substrates, thus making synthetic organofluorine chemistry a fertile ground for
developing new, exciting transformations. In this feature article, we detail our
experiences in methodology, wherein fluorinated substrates have enabled unique
reactivity patterns relative to non-fluorous substrates. Specifically, we
highlight the non-standard chemo- and regio-selectivities imparted by fluorinated
substrates on Pd-catalyzed coupling reactions, nucleophilic addition reactions of
olefins, and Cu-catalyzed decarboxylative fluoroalkylation reactions.
PMID- 28503694
TI - Detection of early osteogenic commitment in primary cells using Raman
spectroscopy.
AB - Major challenges in the development of novel implant surfaces for artificial
joints include osteoblast heterogeneity and the lack of a simple and sensitive in
vitro assay to measure early osteogenic responses. Raman spectroscopy is a label
free, non-invasive and non-destructive vibrational fingerprinting optical
technique that is increasingly being applied to detect biochemical changes in
cells. In this study Raman spectroscopy has been used to obtain bone cell
specific spectral signatures and to identify any changes therein during
osteoblast commitment and differentiation of primary cells in culture. Murine
calvarial osteoblasts (COBs) were extracted and cultured and studied by Raman
spectroscopy over a 14 day culture period. Distinct osteogenic Raman spectra were
identified after 3 days of culture with strong bands detected for mineral:
phosphate nu3 (1030 cm-1) and B-type carbonate (1072 cm-1), DNA (782 cm-1) and
collagen matrix (CH2 deformation at 1450 cm-1) and weaker phosphate bands (948
and 970 cm-1). Early changes were detected by Raman spectroscopy compared to a
standard enzymatic alkaline phosphatase (ALP) assay and gene expression analyses
over this period. Proliferation of COBs was confirmed by fluorescence intensity
measurements using the Picogreen dsDNA reagent. Changes in ALP levels were
evident only after 14 days of culture and mRNA expression levels for ALP, Col1a1
and Sclerostin remained constant during the culture period. Sirius red staining
for collagen deposition also revealed little change until day 14. In contrast
Raman spectroscopy revealed the presence of amorphous calcium phosphate (945-952
cm-1) and carbonated apatite (957-962 cm-1) after only 3 days in culture and
octacalcium phosphate (970 cm-1) considered a transient mineral phase, was
detected after 5 days of COBs culture. PCA analysis confirmed clear separation
between time-points. This study highlights the potential of Raman spectroscopy to
be utilised for the early and specific detection of proliferation and
differentiation changes in primary cultures of bone cells.
PMID- 28503695
TI - Cp*CoIII-catalyzed directed C-H trifluoromethylthiolation of 2-phenylpyridines
and 6-arylpurines.
AB - Cp*CoIII-catalyzed directed C-H trifluoromethylthiolation using N
trifluoromethylthiodibenzenesulfonimide as an electrophilic SCF3 source is
described. 6-Arylpurines, an important structural motif in medicinal chemistry,
and 2-phenylpyridines selectively afforded mono-trifluoromethylthiolated products
in moderate to good yields using an inexpensive first-row transition metal
catalyst.
PMID- 28503697
TI - Low-temperature-selective luminescent mechanochromism of a thienyl gold
isocyanide complex.
AB - The low-temperature-selective mechanochromism of a thienyl gold(i) isocyanide
complex is reported. The as-prepared powder of this complex did not show any
luminescent color changes upon grinding at room temperature. When cooled below
50 degrees C, the powder showed a blue emission in the absence of a phase
transition. Upon grinding this powder below -50 degrees C, a green emission was
observed, which indicates notable mechanochromism that only occurs at low
temperature.
PMID- 28503696
TI - Ion-induced molecular growth in clusters of small hydrocarbon chains.
AB - We report on studies of collisions between 3 keV Ar+ projectile ions and neutral
targets of isolated 1,3-butadiene (C4H6) molecules and cold, loosely bound
clusters of these molecules. We identify molecular growth processes within the
molecular clusters that appears to be driven by knockout processes and that could
result in the formation of (aromatic) ring structures. These types of reactions
are not unique to specific projectile ions and target molecules, but will occur
whenever atoms or ions with suitable masses and kinetic energies collide with
aggregates of matter, such as carbonaceous grains in the interstellar medium or
aerosol nanoparticles in the atmosphere.
PMID- 28503698
TI - Breast reconstruction rate and profile in a Singapore patient population: a
National University Hospital experience.
AB - INTRODUCTION: Breast reconstruction is an integral part of breast cancer
management with the aim of restoring a breast to its natural form. There is
increasing awareness among women that it is a safe procedure and its benefits
extend beyond aesthetics. Our aim was to establish the rate of breast
reconstruction and provide an overview of the patients who underwent breast
reconstruction at National University Hospital (NUH), Singapore. METHODS: We
evaluated factors that impact a patient's decision to proceed with breast
reconstruction, such as ethnicity, age, time and type of implant. We
retrospectively reviewed the medical records of women who had breast cancer and
underwent breast surgery at NUH between 2001 and 2010. RESULTS: The breast
reconstruction rate in this study was 24.3%. There were 241 patients who
underwent breast reconstruction surgeries (including delayed and immediate
procedures) among 993 patients for whom mastectomies were done for breast cancer.
Chinese patients were the largest ethnic group who underwent breast
reconstruction after mastectomy (74.3%). Within a single ethnic patient group,
Malay women had the largest proportion of women undergoing breast reconstruction
(60.0%). The youngest woman in whom cancer was detected in our study was aged 20
years. Malay women showed the greatest preference for autologous tissue breast
reconstruction (92.3%). The median age at cancer diagnosis of our cohort was 46
years. CONCLUSION: We noted increases in the age of patients undergoing breast
reconstruction and the proportion of breast reconstruction cases over the ten
year study period.
PMID- 28503699
TI - Eating psychopathology and psychosocial impairment in patients treated at a
Singapore eating disorders treatment programme.
AB - INTRODUCTION: There is limited data on the psychopathology of eating disorders in
Singapore. This study: (a) described levels of eating psychopathology and
psychosocial impairment among individuals diagnosed with eating disorders at our
hospital; and (b) compared the related psychopathology of these patients.
METHODS: Between 1 August 2010 and 31 July 2012, 257 individuals who met the
diagnostic criteria for eating disorders completed the Eating Disorder
Examination Questionnaire (EDE-Q) and Clinical Impairment Assessment
questionnaire (CIA). RESULTS: A majority of participants were women and of
Chinese ethnicity. Diagnoses included anorexia nervosa (AN; 41.6%), bulimia
nervosa (BN; 29.6%) and eating disorder not otherwise specified (EDNOS; 28.8%).
Mean age at presentation was 20.52 +/- 7.14 years and mean body mass index was
17.84 +/- 4.18 kg/m2. Individuals with AN were significantly younger at
presentation and had shorter duration of untreated illness compared to those with
BN and EDNOS. There were no significant differences in the CIA scores of the
diagnostic groups. Participants with BN scored higher in all subscales of the EDE
Q than those with AN and EDNOS. Our sample scored lower in most subscales of EDE
Q when compared to treatment centres in Sweden, Australia and the United States.
CONCLUSION: Our clinical sample reported lower scores of psychopathology compared
to overseas centres. This could be attributed to the higher percentages of BN and
EDNOS diagnosed in overseas populations. Individuals with AN showed higher levels
of psychopathology in our study compared to patients from the United States.
PMID- 28503700
TI - Venous ultrasonography findings and clinical correlations in 104 Thai patients
with chronic venous insufficiency of the legs.
AB - INTRODUCTION: The pattern of venous reflux in Thai patients with chronic venous
insufficiency (CVI) was studied in correlation with clinical manifestations.
METHODS: Ultrasonography findings and clinical data were prospectively collected
and retrospectively reviewed. RESULTS: CVI was found in 104 legs of 79 patients
(mean age 59.8 +/- 12.5 years; C4: 24.1%, C5: 8.9%, C6: 67.1%). 6.7% of the legs
had a history of deep vein thrombosis (DVT). The prevalence of superficial vein
reflux (SVR), deep vein reflux (DVR), and combined SVR and DVR in 90 legs without
previous venous surgery was 82.2%, 63.3% and 57.8%, respectively. In legs with
SVR, the prevalence of great saphenous vein reflux (GSVR), small saphenous vein
reflux (SSVR), and combined GSVR and SSVR was 91.9%, 33.8% and 25.7%,
respectively. 77.0% of SVR involved the calf segment. For medial ulceration,
79.6% had GSVR and 35.2% had SSVR. For lateral ulceration, 46.7% had SSVR and
33.3% had isolated GSVR. Pulsatile venous signal was found in 3.3% of legs. In 17
legs with ulceration after previous surgical treatment, calf vein reflux
(residual calf great saphenous vein or small saphenous vein) was found in 13
(76.5%) legs. CONCLUSION: Calf vein reflux plays an important role in CVI and in
patients with recurrent ulceration after previous superficial venous surgery.
Although GSVR was present in most patients with CVI in the legs, SSVR may present
in one-third of patients, especially those with lateral ulceration. The high
prevalence of DVR in the absence of DVT and the presence of a pulsatile venous
signal in some patients highlight the incomplete understanding of CVI aetiology.
PMID- 28503701
TI - Incorporating threat in hotspots and coldspots of biodiversity and ecosystem
services.
AB - Spatial prioritization could help target conservation actions directed to
maintain both biodiversity and ecosystem services. We delineate hotspots and
coldspots of two biodiversity conservation features and five regulating and
cultural services by incorporating an indicator of 'threat', i.e. timber harvest
profitability for forest areas in Telemark (Norway). We found hotspots, where
high values of biodiversity, ecosystem services and threat coincide, ranging from
0.1 to 7.1% of the area, depending on varying threshold levels. Targeting of
these areas for conservation follows reactive conservation approaches. In
coldspots, high biodiversity and ecosystem service values coincide with low
levels of threat, and cover 0.1-3.4% of the forest area. These areas might serve
proactive conservation approaches at lower opportunity cost (foregone timber
harvest profits). We conclude that a combination of indicators of biodiversity,
ecosystem services and potential threat is an appropriate approach for spatial
prioritization of proactive and reactive conservation strategies.
PMID- 28503703
TI - Abnormal vestibular-evoked myogenic potentials as an isolated finding of probable
transient labyrinthine ischemia.
PMID- 28503702
TI - Postmortem diagnosis of hyponatremia: case report and literature review.
AB - Hyponatremia is defined as a plasma sodium concentration less than 135 or 130
mEq/L (or mmol/L) and may be responsible for life threatening symptoms that can
be observed in a variety of medical conditions. Cases of fatal hyponatremia have
been reported in both clinical and forensic literature in situations of water
intoxication due to psychogenic polydipsia, amphetamine derivative drug intake,
high-endurance exercise, iatrogenic causes, and exceptional cases of child abuse
by forced water intoxication. Vitreous sodium levels have been determined to be
relatively stable during the early postmortem period and similar to levels found
in normal serum of living subjects. Nevertheless, there are relatively few cases
of fatal hyponatremia described in literature that underwent exhaustive
postmortem biochemical investigations. A case of fatal water intoxication in a
psychiatric patient who underwent medicolegal investigations, including
postmortem biochemistry, was chosen as a starting point to a literature review of
deaths by hyponatremia that may be encountered in the forensic setting.
PMID- 28503704
TI - Use of EEG in critically ill children and neonates in the United States of
America.
AB - The objective of the study was to estimate the proportion of patients who receive
an electroencephalogram (EEG) among five common indications for EEG monitoring in
the intensive care unit: traumatic brain injury (TBI), extracorporeal membrane
oxygenation (ECMO), cardiac arrest, cardiac surgery and hypoxic-ischemic
encephalopathy (HIE). We performed a retrospective cross-sectional descriptive
study utilizing the Kids' Inpatient Database (KID) for the years 2010-2012. The
KID is the largest pediatric inpatient database in the USA and it is based on
discharge reports created by hospitals for billing purposes. We evaluated the use
of electroencephalogram (EEG) or video-electroencephalogram in critically ill
children who were mechanically ventilated. The KID database had a population of
approximately 6,000,000 pediatric admissions. Among 22,127 admissions of
critically ill children who had mechanical ventilation, 1504 (6.8%) admissions
had ECMO, 9201 (41.6%) TBI, 4068 (18.4%) HIE, 2774 (12.5%) cardiac arrest, and
4580 (20.7%) cardiac surgery. All five conditions had a higher proportion of
males, with the highest (69.8%) in the TBI group. The mortality rates ranged from
7.02 to 39.9% (lowest in cardiac surgery and highest in ECMO). The estimated use
of EEG was 1.6% in cardiac surgery, 4.1% in TBI, 7.2% in ECMO, 8.2% in cardiac
arrest, and 12.1% in HIE, with an overall use of 5.8%. Among common indications
for EEG monitoring in critically ill children and neonates, the estimated
proportion of patients actually having an EEG is low.
PMID- 28503706
TI - An eye-tracker controlled cognitive battery: overcoming verbal-motor limitations
in ALS.
AB - We assessed language, attention, executive, and social cognition abilities in a
sample of patients with Amyotrophic Lateral Sclerosis (ALS) by means of a
recently developed cognitive battery based on oculomotor control with eye
tracking (ET) technology. Twenty-one ALS patients and 21 age- and education
matched healthy subjects underwent the ET-based cognitive assessment, together
with the standard cognitive screening tools [Frontal Assessment Battery (FAB);
Montreal Cognitive Assessment (MoCA); and Digit Sequencing Task]. Psychological
measures of anxiety (State-Trait Anxiety Inventory-Y) and depression (Beck
Depression Inventory) were also collected, and an ET usability questionnaire was
administered. For patients, clinical and respiratory examinations were also
performed, together with behavioural assessment (Frontal Behavioural Inventory).
The developed battery discriminated among patients and controls with regard to
measures of verbal fluency, frontal abilities, and social cognition. Measures of
diagnostic utility confirmed a higher diagnostic accuracy of such ET-based tests
with respect to FAB; similar diagnostic accuracy emerged when comparing them to
the other standard cognitive tools (MoCA, WM). Usability ratings about the ET
tests were comparable among the two groups. The ET-based neuropsychological
battery demonstrated good levels of diagnostic accuracy and usability in a
clinical population of non-demented ALS patients, compared to matched healthy
controls. Future studies will be aimed at further investigate validity and
usability components by recruiting larger sample of patients, both in moderate-to
severe stages of the disease and affected by more severe cognitive impairment.
PMID- 28503705
TI - Muscle MRI in neutral lipid storage disease (NLSD).
AB - Neutral lipid storage disease (NLSD) is a rare inherited disorder of lipid
metabolism resulting in lipid droplets accumulation in different tissues.
Skeletal muscle could be affected in both two different form of disease: NLSD
with myopathy (NLSD-M) and NLSD with ichthyosis (NLSD-I). We present the muscle
imaging data of 12 patients from the Italian Network for NLSD: ten patients
presenting NLSD-M and two patients with NLSD-I. In NLSD-M gluteus minimus,
semimembranosus, soleus and gastrocnemius medialis in the lower limbs and
infraspinatus in the upper limbs were the most affected muscles. Gracilis,
sartorius, subscapularis, pectoralis, triceps brachii and sternocleidomastoid
were spared. Muscle involvement was not homogenous and characteristic "patchy"
replacement was observed in at least one muscle in all the patients. Half of the
patients showed one or more STIR positive muscles. In both NLSD-I cases muscle
involvement was not observed by T1-TSE sequences, but one of them showed positive
STIR images in more than one muscle in the leg. Our data provides evidence that
muscle imaging can identify characteristic alterations in NLSD-M, characterized
by a specific pattern of muscle involvement with "patchy" areas of fatty
replacement. Larger cohorts are needed to assess if a distinct pattern of muscle
involvement exists also for NLSD-I.
PMID- 28503707
TI - The value of ultrasound in diagnosing extracranial large-vessel vasculitis
compared to FDG-PET/CT: A retrospective study.
AB - Large-vessel vasculitis (LVV) is a group of diseases mainly comprised of giant
cell arteritis (GCA), Takayasu arteritis, and a series of rare diseases like
Behcet's disease, IgG4-related disease, infectious aortitis, and other unfrequent
entities. Besides clinical and laboratory features, Doppler sonography (DS) can
assist in establishing the diagnosis. Its diagnostic sensitivity has been
evaluated in various studies, most of them, however, in temporal arteritis (TA)
respectively in LVV with involvement of the temporal artery. Little is known in
extracranial LVV. We retrospectively evaluated the diagnostic accuracy of DS in
30 patients with extracranial, non-temporal LVV using the highly sensitive PET/CT
as method of reference in comparison to 20 controls who were found to have no
LVV. We investigated ten arterial sites and documented the presence of the
sonographic halo sign. Sensitivities of DS for LVV were highest in the subclavian
and axillary arteries (71.4%/72.2%) and low in the abdominal aorta (26.1%) and
the common femoral artery (16.7%). DS detected 24 out of 30 cases of LVV (overall
sensitivity 80.0%). The LVV cases where DS was completely negative did not
significantly differ in leukocyte count, C-reactive protein, or erythrocyte
sedimentation rate from LVV cases with positive DS. DS is a potent method in
diagnosing extracranial LVV especially in the axillary and the subclavian
arteries. Aortic, intraabdominal, and lower extremity artery manifestations,
however, are often missed by DS. A second imaging modality (e.g., PET/CT) is
therefore required.
PMID- 28503709
TI - Morphological and molecular characterization of Sarcocystis arctica-like
sarcocysts from the Arctic fox (Vulpes lagopus) from Alaska, USA.
AB - The muscles of herbivores commonly harbor sarcocysts of parasites belonging to
species in the genus Sarcocystis, but such muscle parasites are rare in
carnivores. Here, we report Sarcocystis arctica-like sarcocysts in muscles of
Arctic foxes (Vulpes lagopus) from Alaska, USA, for the first time. The tongues
of 56 foxes were examined for Sarcocystis infection using several methods.
Sarcocystis bradyzoites were detected in pepsin digests of 13 (23.2%), and
sarcocysts were found in histological sections stained with hematoxylin and eosin
(HE) of 9 (16.0%). By light microscopy, sarcocysts were up to 4 mm long and up to
245 MUm wide. In HE-stained sections, the sarcocyst wall appeared smooth and up
to 1.5 MUm thick without visible protrusions. By transmission electron
microscopy, the sarcocyst wall had a wavy parasitophorous vacuolar membrane (pvm)
folded as pleomorphic villar protrusions (vp), sometimes with anastomoses of
villar tips. The vp and the ground substance (gs) layer were smooth and without
microtubules. The gs was up to 2.0 MUm thick. The total width of the wall
including vp and the gs was up to 4.0 MUm. The vp were up to 3.0 MUm long and
most closely resembled "type 9c." All sarcocysts were mature and contained
numerous 8.1 * 2.1 MUm sized bradyzoites. Molecular characterization (at 18S
rDNA, 28S rDNA, ITS-1, and cox1) showed the highest affinity for S. arctica of
the Arctic fox (V. lagopus) from Norway. In the present investigation, we provide
evidence that sarcocysts are common in tongues of Alaskan Arctic foxes suggesting
that these carnivores are serving as intermediate hosts, and we also provide
ultrastructure of S. arctica from the Arctic fox for the first time.
PMID- 28503710
TI - Characterization of a new multifunctional beta-glucosidase from Musca domestica.
AB - OBJECTIVE: To engineer Pichia pastoris for heterologous production of cellulase
from Musca domestica and explore its potential for industrial applications.
RESULTS: A new beta-glucosidase gene (bg), encoding 562 amino acids, was cloned
from M. domestica by using rapid amplification of cDNA ends. The gene bg was
linked to pPICZalphaA and expressed in P. pastoris with a yield of 500 mg l-1.
The enzyme has the maximum activity with 27.6 U mg-1 towards cellulose. The beta
glucosidase has stable activity from 20 to 70 degrees C and can tolerate one
mole glucose. It has the maximum activities for salicin (25.9 +/- 1.8 U mg-1),
cellobiose (40.1 +/- 2.3 U mg-1) and cellulose (27.6 +/- 3.5 U mg-1). The wide
range substrate activities of the beta-glucosidase were further verified by
matrix-assisted laser desorption/ionization mass spectra. Structural analysis
shows that the beta-glucosidase belongs to glycoside hydrolase family Iota and
possesses O-glycosylation sites. CONCLUSIONS: Thus, a multifunctional beta
glucosidase was expressed from M. domestica and provides a potential tool for
industrial application of cellulose.
PMID- 28503712
TI - Dupilumab Improves General Health-Related Quality-of-Life in Patients with
Moderate-to-Severe Atopic Dermatitis: Pooled Results from Two Randomized,
Controlled Phase 3 Clinical Trials.
AB - INTRODUCTION: Patients with moderate-to-severe atopic dermatitis (AD) report a
multidimensional disease burden that includes impaired health-related quality-of
life (HRQoL). Changes in overall health status and specific dimensions that
contribute to HRQoL were evaluated in adults with moderate-to-severe AD who
participated in phase 3 clinical trials of dupilumab, which is a fully human
monoclonal antibody that inhibits signaling of cytokines IL-4 and IL-13. METHODS:
Two dupilumab phase 3 clinical trials of identical design included the 5
dimension 3-level EuroQol (EQ-5D) as a measure of HRQoL. EQ-5D data from the two
trials were pooled in an analysis that, using analysis of covariance, compared
subcutaneous dupilumab 300 mg once weekly (qw) or every 2 weeks (q2w) versus
placebo for EQ-5D utility score change from baseline overall and for clinical
responders. The proportions of patients who reported different levels of problems
on the individual dimension of the EQ-5D were also compared by treatment group.
RESULTS: Patients (n = 1379) were 57.9% male with a mean (SD) age of 38.3 (14.3)
years; baseline EQ-5D utility scores ranged from 0.611 to 0.629 across treatment
groups. EQ-5D least squares mean change from baseline at week 16 was 0.031 with
placebo, and was significantly greater with dupilumab qw (0.207) and q2w (0.210)
(both P < 0.0001), which exceeded the minimal clinically important difference and
resulted in scores that approached population norms. Changes from baseline among
patients who achieved AD clinical response were greater than changes among the
total population. Improvements were driven by the individual EQ-5D dimensions
with the greatest burden at baseline (i.e., pain/discomfort, anxiety/depression
and usual activities). CONCLUSION: In adults with moderate-to-severe AD,
dupilumab resulted in improvements in HRQoL that were statistically significant
relative to placebo and were clinically meaningful. FUNDING: Sanofi and Regeneron
Pharmaceuticals, Inc. TRIAL REGISTRATION: ClinicalTrials.gov identifiers,
NCT02277743 and NCT02277769, EudraCT Numbers 2014-001198-15 and 2014-002619-40.
PMID- 28503711
TI - Bioactivity Improvement of Olea europaea Leaf Extract Biotransformed by
Wickerhamomyces anomalus Enzymes.
AB - Olive leaves represent a quantitatively significant by-product of agroindustry.
They are rich in phenols, mainly oleuropein, which can be hydrolyzed into several
bioactive compounds, including hydroxytyrosol. In this study, water extract from
olive leaves 'Biancolilla' was analyzed for polyphenol profile, DPPH (2,2
diphenyl-1-picrylhydrazyl) radical scavenging activity and protective effect on
differentiated Caco-2 cells. The efficacy of two enzymatic treatments in
promoting the release of bioactive phenols was investigated: a) enzymatic extract
from Wickerhamomyces anomalus, characterized by beta-glucosidase and esterase
activities; b) commercial beta-glucosidase. Composition and bioactivity of the
resulting extracts were compared. The results showed that the yeast-treated
extract presented hydroxytyrosol content and DPPH radical scavenging activity
comparable to those obtained using commercial beta-glucosidase; however, it was
showed the additional presence of hydroxycinnamic acids. In experiments on Caco-2
cells, the leaf extracts promoted the recovery of cell membrane barrier at
different minimum effective concentrations. The high specificity of W. anomalus
enzymatic extract may represent an effective tool for the release of bioactive
phenols from olive by-products.
PMID- 28503708
TI - Stress and the nonsense-mediated RNA decay pathway.
AB - Cells respond to internal and external cellular stressors by activating stress
response pathways that re-establish homeostasis. If homeostasis is not achieved
in a timely manner, stress pathways trigger programmed cell death (apoptosis) to
preserve organism integrity. A highly conserved stress pathway is the unfolded
protein response (UPR), which senses excessive amounts of unfolded proteins in
the ER. While a physiologically beneficial pathway, the UPR requires tight
regulation to provide a beneficial outcome and avoid deleterious consequences.
Recent work has demonstrated that a conserved and highly selective RNA
degradation pathway-nonsense-mediated RNA decay (NMD)-serves as a major regulator
of the UPR pathway. NMD degrades mRNAs encoding UPR components to prevent UPR
activation in response to innocuous ER stress. In response to strong ER stress,
NMD is inhibited by the UPR to allow for a full-magnitude UPR response. Recent
studies have indicated that NMD also has other stress-related functions,
including promoting the timely termination of the UPR to avoid apoptosis; NMD
also regulates responses to non-ER stressors, including hypoxia, amino-acid
deprivation, and pathogen infection. NMD regulates stress responses in species
across the phylogenetic scale, suggesting that it has conserved roles in shaping
stress responses. Stress pathways are frequently constitutively activated or
dysregulated in human disease, raising the possibility that "NMD therapy" may
provide clinical benefit by downmodulating stress responses.
PMID- 28503713
TI - Development and refinement of the WAItE: a new obesity-specific quality of life
measure for adolescents.
AB - BACKGROUND: Few weight-specific outcome measures, developed specifically for
obese and overweight adolescents, exist and none are suitable for the elicitation
of utility values used in the assessment of cost effectiveness. OBJECTIVES: The
development of a descriptive system for a new weight-specific measure. METHODS:
Qualitative interviews were conducted with 31 treatment-seeking (above normal
weight status) and non-treatment-seeking (school sample) adolescents aged 11-18
years, to identify a draft item pool and associated response options. 315
eligible consenting adolescents, aged 11-18 years, enrolled in weight management
services and recruited via an online panel, completed two version of a long-list
29-item descriptive system (consisting of frequency and severity response
scales). Psychometric assessments and Rasch analysis were applied to the draft 29
item instrument to identify a brief tool containing the best performing items and
associated response options. RESULTS: Seven items were selected, for the final
item set; all displayed internal consistency, moderate floor effects and the
ability to discriminate between weight categories. The assessment of
unidimensionality was supported (t test statistic of 0.024, less than the 0.05
threshold value). CONCLUSIONS: The Weight-specific Adolescent Instrument for
Economic-evaluation focuses on aspects of life affected by weight that are
important to adolescents. It has the potential for adding key information to the
assessment of weight management interventions aimed at the younger population.
PMID- 28503714
TI - Depression severity and concentration difficulties are independently associated
with HRQOL in patients with unipolar depressive disorders.
AB - PURPOSE: Cognitive impairment is a core feature of major depressive disorder
(MDD), and dysfunctions in this area strongly contribute to MDD-associated
disability. Whether cognitive impairment has an independent clinical course and a
unique impact on HRQOL is still debated. We sought to characterize the
relationship between depression severity and HRQOL, evaluating the burden of
concentration difficulties on HRQOL. METHODS: Six hundred ninety-two patients
with unipolar depressive disorders recruited in 19 Italian centers answered a
self-administered survey (SF-12 questionnaire, socio-demographic information). A
psychiatrist completed a standardized data collection form encompassing a
depression severity scale (MADRS) and clinical information. RESULTS: There was a
strong graded association between the severity of depressive symptoms and both
the physical (omega 2 = 0.13; p < 0.01) and mental (omega 2 = 0.34; p < 0.01) SF
12 domains. Additionally, we observed a strong association between concentration
difficulties and all HRQOL outcomes independent of other symptoms of depression
and robust to adjustment for possible confounders. CONCLUSIONS: Our data
corroborate previous findings suggesting that cognitive impairment is a feature
of unipolar depressive disorders partially independent of the severity of other
symptoms, and may represent a specific target of therapy with a strong impact on
patients' functioning and quality of life.
PMID- 28503715
TI - Deficiency of Interleukin-1 Receptor Antagonist (DIRA): Report of the First
Indian Patient and a Novel Deletion Affecting IL1RN.
AB - PURPOSE: Deficiency of interleukin-1 receptor antagonist (DIRA) is a rare life
threatening autoinflammatory disease caused by autosomal recessive mutations in
IL1RN. DIRA presents clinically with early onset generalized pustulosis,
multifocal osteomyelitis, and elevation of acute phase reactants. We evaluated
and treated an antibiotic-unresponsive patient with presumed DIRA with
recombinant IL-1Ra (anakinra). The patient developed anaphylaxis to anakinra and
was subsequently desensitized. METHODS: Genetic analysis of IL1RN was undertaken
and treatment with anakinra was initiated. RESULTS: A 5-month-old Indian girl
born to healthy non-consanguineous parents presented at the third week of life
with irritability, sterile multifocal osteomyelitis including ribs and clavicles,
a mild pustular rash, and elevated acute phase reactants. SNP array of the
patient's genomic DNA revealed a previously unrecognized homozygous deletion of
approximately 22.5 Kb. PCR and Sanger sequencing of the borders of the deleted
area allowed identification of the breakpoints of the deletion, thus confirming a
homozygous 22,216 bp deletion that spans the first four exons of IL1RN. Due to a
clinical suspicion of DIRA, anakinra was initiated which resulted in an
anaphylactic reaction that triggered desensitization with subsequent marked and
sustained clinical and laboratory improvement. CONCLUSION: We report a novel DIRA
causing homozygous deletion affecting IL1RN in an Indian patient. The mutation
likely is a founder mutation; the design of breakpoint-specific primers will
enable genetic screening in Indian patients suspected of DIRA. The patient
developed anaphylaxis to anakinra, was desensitized, and is in clinical remission
on continued treatment.
PMID- 28503716
TI - Dietary inflammatory index and non-Hodgkin lymphoma risk in an Italian case
control study.
AB - BACKGROUND: While dietary factors have been shown to play an important etiologic
role in non-Hodgkin lymphoma (NHL), little is known about the association between
inflammatory properties of diet and NHL risk. METHODS: We explored the
association between the dietary inflammatory index (DII) and NHL risk in a
multicenter Italian case-control study conducted between 1999 and 2014. Cases
were 536 subjects with incident, histologically confirmed NHL from three areas in
Italy. Controls were 984 subjects admitted to the same network of hospitals as
the cases for acute, nonmalignant conditions, unrelated to diet. DII scores were
computed based on 30 nutrients and food items assessed using a reproducible and
validated 78-item food-frequency questionnaire. Odds ratios (ORs) were estimated
through logistic regression models adjusting for age, total energy intake, and
other recognized confounding factors. RESULTS: Subjects in the highest quartile
of DII scores (i.e., with the most pro-inflammatory diets) had a higher risk of
NHL compared with subjects in the lowest quartile (i.e., with the most anti
inflammatory diets) (ORQuartile4vs1 1.61, 95% confidence interval CI 1.07-2.43; p
trend = 0.01). Stratified analyses produced stronger associations between DII and
NHL among males (ORQuartile4vs1 2.14; 95% CI 1.25-3.67) with significant
heterogeneity (p value = 0.02); when analyzed by histologic subtype, a
significant association was observed with diffuse large B-cell lymphoma
(ORQuartile4vs1 1.84; 95% CI 1.09-3.10). CONCLUSION: A pro-inflammatory diet, as
indicated by higher DII scores, is associated with elevated odds of NHL,
especially among males.
PMID- 28503718
TI - Photodithazine photodynamic effect on viability of 9L/lacZ gliosarcoma cell line.
AB - Even with the advances of conventional treatment techniques, the nervous system
cancer prognosis is still not favorable to the patient which makes alternative
therapies needed to be studied. Photodynamic therapy (PDT) is presented as a
promising therapy, which employs a photosensitive (PS) agent, light wavelength
suitable for the PS agent, and molecular oxygen, producing reactive oxygen
species in order to induce cell death. The aim of this study is to observe the
PDT action in gliosarcoma cell using a chlorin (Photodithazine, PDZ). The
experiments were done with 9L/lacZ lineage cells, grown in a DMEM medium
supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin solution
and put in a culture chamber at 37 degrees C with an atmosphere of 5% CO2. The
PS agent used was the PDZ to an LED light source device (Biopdi/IRRAD-LED 660) in
the 660-nm region. The location of the PS agent was analyzed by fluorescence
microscopy, and cell viability was analyzed by MTT assay (mitochondrial
activity), exclusion by trypan blue (cell viability), and morphological
examination through an optical microscope (Leica MD 2500). In the analysis of the
experiments with PDZ, there was 100% cell death at different concentrations and
clear morphological differences in groups with and without treatment.
Furthermore, it was observed that the photodithazine has been focused on all
nuclear and cytoplasmic extension; however, it cannot be said for sure whether
the location is in the inside core region or on the plasma membrane. In general,
the PDZ showed a promising photosensitive agent in PDT for the use of
gliosarcoma.
PMID- 28503717
TI - A Review of the Current Challenges Associated with the Development of an
Artificial Pancreas by a Double Subcutaneous Approach.
AB - INTRODUCTION: Patients with diabetes type 1 (DM1) struggle daily to achieve good
glucose control. The last decade has seen a rush of research groups working
towards an artificial pancreas (AP) through the application of a double
subcutaneous approach, i.e., subcutaneous (SC) continuous glucose monitoring
(CGM) and continuous subcutaneous insulin infusion. Few have focused on the
fundamental limitations of this approach, especially regarding outcome measures
beyond time in range. METHODS: Based on insulin physiology, the limitations of
CGM, SC insulin absorption, meal challenge, and physical activity in DM1
patients, we discuss the limitations of the double SC approach. Finally, we
discuss safety measures and the achievements reported in some recent AP studies
that have utilized the double SC approach. RESULTS: Most studies show that a
double SC AP increases the time in range compared to a sensor-augmented insulin
pump and shortens the time in hypoglycemia. Despite these achievements, the
proportion of time spent in hyperglycemia is still roughly 20-40%, and
hypoglycemia is still present 1-4% of the time. The main factors limiting further
progress are the latency of SC CGM (at least 5-10 min) and the slow
pharmacokinetics of SC-delivered fast-acting insulin. The maximum blood insulin
level is reached after 45 min and the maximum glucose-lowering effect is observed
after 1.5-2 h, while the glucose-lowering effect lasts for at least 5 h.
CONCLUSIONS: Although using a double SC AP leads to significant improvements in
glucose control, the SC approach has severe limitations that hamper further
progress towards a robust AP.
PMID- 28503719
TI - Radiation and depression associated with complications of tissue expander
reconstruction.
AB - PURPOSE: Rates of implant failure, wound healing delay, and infection are higher
in patients having radiation therapy (RT) after tissue expander (TE) and
permanent implant reconstruction. We investigated pretreatment risk factors for
TE implant complications. PATIENTS AND METHODS: 127 breast cancer patients had TE
reconstruction and radiation. For 85 cases of bilateral TE reconstruction, the
non-irradiated breast provided an internal control. Comparison of differences in
means for continuous variables used analysis of variance, then multiple pairwise
comparisons with Bonferroni correction of p value. RESULTS: Mean age was 53 +/-
10.1 years with 14.6% African-American. Twelve (9.4%) were BRCA positive (9
BRCA1, 4 BRCA2, 1 Both). Complications were: Grade 0 (no complication; 43.9%),
Grade 1 (tightness and/or drifting of implant or Baker Grade II capsular
contracture; 30.9%), Grade 2 (infection, hypertrophic scarring, or incisional
necrosis; 9.8%), Grade 3 (Baker Grade III capsular contracture, wound dehiscence,
or impending exposure of implant; 5.7%), Grade 4 (implant failure, exchange of
implant, or Baker Grade IV capsular contracture; 9.8%). 15.3% (19 cases)
experienced Grade 3 or 4 complication and 9.8% (12 cases) had Grade 4
complication. Considering non-irradiated breasts, there were two (1.6%) Grade 3-4
complications. For BMI, there was no significant difference by category as
defined by the CDC (p = 0.91). Patients with depression were more likely to
experience Grade 3 or 4 complication (29.4 vs 13.2%; p = 0.01). Using multiple
logistic regression to predict the probability of a Grade 3 or 4 complications in
patients with depression were found to be 4.2 times more likely to have a Grade 3
or 4 complication (OR = 4.2, p = 0.03). CONCLUSIONS: Higher rates of TE
reconstruction complications are expected in patients receiving radiotherapy. An
unexpected finding was that patients reporting medical history of depression
showed statistically significant increase in complication rates.
PMID- 28503720
TI - Contribution of germline mutations in cancer predisposition genes to tumor
etiology in young women diagnosed with invasive breast cancer.
AB - PURPOSE: Although breast cancer in young women accounts for <10% of diagnoses
annually, tumors in young patients exhibit more aggressive characteristics and
higher mortality rates. Determination of the frequency of germline mutations in
cancer predisposition genes is needed to improve the understanding of breast
cancer etiology in young women. METHODS: All female patients enrolled in the
Clinical Breast Cancer Project between 2001 and 2015 and diagnosed with invasive
breast cancer before age 40 were included in this study. Family history was
classified using the NCCN Familial Risk Assessment guidelines. Targeted
sequencing of 94 cancer predisposition genes was performed using peripheral blood
DNA. Variants were detected using VariantStudio and classified using ClinVar.
RESULTS: Seven percent (141/1980) of patients were young women and 44 had a
significant family history. Sequencing was completed for 118 women with genomic
DNA. Pathogenic mutations were present in 27 patients: BRCA1 (n = 10), BRCA2 (n =
12), TP53 (n = 1), and CHEK2 (n = 4). Mutations classified as pathogenic were
also detected in APC (n = 1) and MUTYH (n = 2). Variants of uncertain
significance (VUS) were detected in an additional 17 patients in ten genes.
DISCUSSION: Pathogenic mutations in high- and moderate-risk breast cancer genes
were detected in 23% of young women with an additional 3% having pathogenic
mutations in colon cancer predisposition genes. VUS were observed in 14% of women
in genes such as ATM, BRCA2, CDH1, CHEK2, and PALB2. Identification of those non
genetic factors is critical to reduce the burden of breast cancer in this
population.
PMID- 28503721
TI - Limited influence of germline genetic variation on all-cause mortality in women
with early onset breast cancer: evidence from gene-based tests, single-marker
regression, and whole-genome prediction.
AB - PURPOSE: Women diagnosed with breast cancer have heterogeneous survival outcomes
that cannot be fully explained by known prognostic factors, and germline
variation is a plausible but unconfirmed risk factor. METHODS: We used three
approaches to test the hypothesis that germline variation drives some differences
in survival: mortality loci identification, tumor aggressiveness loci
identification, and whole-genome prediction. The 2954 study participants were
women diagnosed with breast cancer before age 50, with a median follow-up of 15
years who were genotyped on an exome array. We first searched for loci in gene
regions that were associated with all-cause mortality. We next searched for loci
in gene regions associated with five histopathological characteristics related to
tumor aggressiveness. Last, we also predicted 10-year all-cause mortality on a
subset of 1903 participants (3,245,343 variants after imputation) using whole
genome prediction methods. RESULTS: No risk loci for mortality or tumor
aggressiveness were identified. This null result persisted when restricting to
women with estrogen receptor-positive tumors, when examining suggestive loci in
an independent study, and when restricting to previously published risk loci.
Additionally, the whole-genome prediction model also found no evidence to support
an association. CONCLUSION: Despite multiple complementary approaches, our study
found no evidence that mortality in women with early onset breast cancer is
influenced by germline variation.
PMID- 28503722
TI - Fertility preservation with ovarian stimulation and time to treatment in women
with stage II-III breast cancer receiving neoadjuvant therapy.
AB - PURPOSE: To determine whether fertility preservation with ovarian stimulation
(OS) results in treatment delay in breast cancer (BC) patients receiving
neoadjuvant therapy (NAT). METHODS: This is a retrospective study of women
screened for the prospective neoadjuvant ISPY2 trial at the University of
California San Francisco. All patients were <43, had stage II-III BC, and
received neoadjuvant therapy. Time to initiation of NAT was compared between
women who underwent OS (STIM) and women who did not (control). Patient and tumor
characteristics, as well as oncologic outcomes, were compared between STIM and
control groups. RESULTS: 82 patients were included (34 STIM and 48 control). STIM
patients were overall younger (mean = 35 vs. 36.9 years old, p = 0.06), and more
likely to be childless (79.4 vs 31.2%, p < 0.0001) than controls. Mean time from
diagnosis to initiation of NAT was 40 days, with no significant difference
between STIM and control groups (mean 39.8 days vs 40.9 days, p = 0.75). Mean
time from diagnosis to fertility consultation was 16.3 days. With median follow
up of 79 months, 16 (19.5%) patients have recurred or died from BC. Rates of pCR,
recurrence, and death were similar in both groups. Six of 34 STIM patients have
undergone embryo transfer, resulting in one patient with two live births.
CONCLUSION: Fertility preservation with OS can be performed in the neoadjuvant
setting without delay in initiation of systemic therapy and should be discussed
with all early-stage BC patients of reproductive age.
PMID- 28503723
TI - Risk of death from cardiovascular disease following breast cancer: a systematic
review.
AB - PURPOSE: Breast cancer incidence and survival is high, which results in high
prevalence of breast cancer survivors. The risk of (death from) cardiovascular
disease (CVD) is higher in patients exposed to cardiotoxic treatments, in
particular if they have pre-existing CVD risk factors. This study systematically
summarized the risk of death from CVD following breast cancer. METHODS: Databases
of Medline, Embase, and the Cochrane Library were systematically searched using
the following terms and synonyms: breast cancer, cardiovascular disease, and
cause of death. Articles reporting on both risk and risk factors of CVD mortality
following breast cancer were eligible for inclusion. The methodological quality
of each article was assessed using the Newcastle Ottawa quality assessment scale
for cohort studies. RESULTS: Fourteen articles were included assessing the risk
of CVD mortality among 1,217,910 women with breast cancer. The methodological
quality was high for the majority of the studies. Studies were heterogeneous in
design, study population, length of follow-up, CVD outcomes, and risk factors.
1.6-10.4% of all women with breast cancer died of CVD. Women with breast cancer
had a higher risk of CVD mortality than women from the general population. The
risk of CVD mortality was higher among women with breast cancer with older age at
diagnosis, left-sided tumor, diagnosis in an earlier calendar period, and black
ethnic origin. CONCLUSIONS: CVD is an important cause of death following breast
cancer. Identification of patients at high risk of CVD is important to optimize
CVD prevention and tailor breast cancer treatment.
PMID- 28503724
TI - Root resorption during orthodontic treatment with Invisalign(r): a radiometric
study.
AB - BACKGROUND: Root resorption (RR) is described as a permanent loss of tooth
structure from the root apex. Many reports in the literature indicate that
orthodontically treated patients are more likely to have severe apical root
shortening, interesting mostly maxillary, followed by mandibular incisors. The
aim of the study was to investigate the incidence and severity of RR in adult
patients treated with aligners. The study group consisted of 71 class I adult
healthy patients (mean age 32.8 +/- 12.7) treated with aligners (Invisalign(r),
Align Technologies, Santa Clara, CA, USA). All incisors, canines, upper first
premolars, and first molars were assessed. Root and crown lengths of 1083 teeth
were measured in panoramic radiographs at the beginning (T0) and at the end (T1)
of clear aligner therapy. Individual root-crown ratio (RCR) of each tooth and
therefore the relative changes of RCR (rRCR) were determined. A decrease of rRCR
was assessed as a reduction of the root length during treatment. RESULTS: All
patients had a minimum of one teeth affected with a reduction of root length, on
average 6.38 +/- 2.28 teeth per patient. Forty one, 81% of the 1083, measured
teeth presented a reduction of the pre-treatment root length. A reduction in
percentage of >0% up to 10% was found in 25.94% (n = 281), a distinct reduction
of >10% up to 20% in 12.18% (n = 132) of the sample. 3.69% (n = 40) of the teeth
were affected with a considerable reduction (>20%). CONCLUSIONS: Orthodontic
treatment with Invisalign(r) aligners could lead to RR. However, its incidence
resulted to be very similar to that described for orthodontic light forces, with
an average percentage of RR < 10% of the original root length.
PMID- 28503725
TI - Posterior teeth angulation in non-extraction and extraction treatment of anterior
open-bite patients.
AB - BACKGOUND: This study cephalometrically evaluated the posterior teeth angulation
changes of anterior open-bite non-extraction and extraction treatment in the
permanent dentition, with anterior vertical elastics. METHODS: The sample
consisted of initial and final lateral headfilms of 60 patients divided into 2
groups: Group 1 consisted of 30 patients treated with non-extraction with an
initial mean age of 15.26 years and treated with fixed appliances for a mean
period of 2.46 years. Group 2 consisted of 30 patients treated with extractions,
with an initial mean age of 14.03 years, and treated with fixed appliances for a
mean period of 2.49 years. Within-group treatment changes were evaluated with
paired t tests. Results were considered statistically significant at P < 0.05.
RESULTS: The mandibular posterior teeth were significantly uprighted in both
groups with both treatment protocols. CONCLUSIONS: Correction of anterior open
bite with either non-extraction or extractions with continuous archwires and
vertical anterior elastics uprights the mandibular posterior teeth.
PMID- 28503727
TI - Serotonin-norepinephrine reuptake inhibitors and the influence of binding
affinity (Ki) on analgesia.
AB - WHAT IS KNOWN AND OBJECTIVE: Serotonin-norepinephrine reuptake inhibitors (SNRIs)
are commonly used for various psychiatric conditions and neuropathic pain
syndromes. SNRIs inhibit the reuptake of serotonin (5-HT) and norepinephrine
(NE); however, NE reuptake inhibition is thought to be the primary mediator for
their analgesic effect. COMMENT: Key differences in pharmacodynamics and receptor
affinities exist between SNRIs. The selectivity for each monoamine differs among
SNRIs based on the agent's affinity and activity at the monoamine reuptake
transporter. We review differences in receptor affinities and monoamine
selectivity among SNRIs and the corresponding clinical impact. WHAT IS NEW AND
CONCLUSION: The varying selectivity for 5-HT and NE among the SNRIs may help
explain the therapeutic dosing required for neuropathic pain as well as dose
related adverse effects. It is important to understand the pharmacologic
differences among SNRIs, in addition to the data from clinical trials, to guide
their safe and effective use.
PMID- 28503728
TI - Female undergraduate's perceptions of intrusive behavior in 12 countries.
AB - The present study examines young women's (N = 1,734) perceptions of the
unacceptability of 47 intrusive activities enacted by men. Female undergraduate
psychology students from 12 countries (Armenia, Australia, England, Egypt,
Finland, India, Indonesia, Italy, Japan, Portugal, Scotland, Trinidad) indicated
which of 47 intrusive activities they considered to be unacceptable. Responses
were compared with parasite-stress values, a measure of global gender equality
and Hofstede's dimensions of national cultures. There was no unanimous agreement
on any of the items, even for those relating to forced sexual violence. Cluster
analysis yielded four clusters: "Aggression and surveillance" (most agreement
that the constituent items were unacceptable), "Unwanted attention," "Persistent
courtship and impositions," and "Courtship and information seeking" (least
agreement that the constituent items were unacceptable). There were no
significant relationships between the "Aggression and surveillance" or "Courtship
and information seeking" clusters and the measure of gender equality, Hofstede's
dimensions of national cultures or the measure of parasite stress. For the
"Unwanted attention" and "Persistent courtship and impositions" clusters, women
residing in countries with higher gender inequality and higher parasite-stress
were less accepting of behavior associated with uncommitted sexual relations, and
women in more individualistic societies with higher levels of gender equality
were less accepting of monitoring activities. Culture may take precedence over
personal interpretations of the unacceptability of intrusive behavior that is not
obviously harmful or benign in nature.
PMID- 28503726
TI - Baroreflex dysfunction and augmented sympathetic nerve responses during mental
stress in veterans with post-traumatic stress disorder.
AB - KEY POINTS: Patients with post-traumatic stress disorder (PTSD) are at a
significantly higher risk of developing hypertension and cardiovascular disease.
The mechanisms underlying this increased risk are not known. Studies have
suggested that PTSD patients have an overactive sympathetic nervous system (SNS)
that could contribute to cardiovascular risk; however, sympathetic function has
not previously been rigorously evaluated in PTSD patients. Using direct
measurements of sympathetic nerve activity and pharmacological manipulation of
blood pressure, we show that veterans with PTSD have augmented SNS and
haemodynamic reactivity during both combat-related and non-combat related mental
stress, impaired sympathetic and cardiovagal baroreflex sensitivity, and
increased inflammation. Identifying the mechanisms contributing to increased
cardiovascular (CV) risk in PTSD will pave the way for developing interventions
to improve sympathetic function and reduce CV risk in these patients. ABSTRACT:
Post-traumatic stress disorder (PTSD) is associated with increased cardiovascular
(CV) risk. We tested the hypothesis that PTSD patients have augmented sympathetic
nervous system (SNS) and haemodynamic reactivity during mental stress, as well as
impaired arterial baroreflex sensitivity (BRS). Fourteen otherwise healthy
Veterans with combat-related PTSD were compared with 14 matched Controls without
PTSD. Muscle sympathetic nerve activity (MSNA), continuous blood pressure (BP)
and electrocardiography were measured at baseline, as well as during two types of
mental stress: combat-related mental stress using virtual reality combat
exposure (VRCE) and non-combat related stress using mental arithmetic (MA). A
cold pressor test (CPT) was administered for comparison. BRS was tested using
pharmacological manipulation of BP via the Modified Oxford technique at rest and
during VRCE. Blood samples were analysed for inflammatory biomarkers. Baseline
characteristics, MSNA and haemodynamics were similar between the groups. In PTSD
vs. Controls, MSNA (+8.2 +/- 1.0 vs. +1.2 +/- 1.3 bursts min-1 , P < 0.001) and
heart rate responses (+3.2 +/- 1.1 vs. -2.3 +/- 1.0 beats min-1 , P = 0.003) were
significantly augmented during VRCE. Similarly, in PTSD vs. Controls, MSNA
(+21.0 +/- 2.6 vs. +6.7 +/- 1.5 bursts min-1 , P < 0.001) and diastolic BP
responses (+6.3 +/- 1.0 vs. +3.5 +/- 1.0 mmHg, P = 0.011) were significantly
augmented during MA but not during CPT (P = not significant). In the PTSD group,
sympathetic BRS (-1.2 +/- 0.2 vs. -2.0 +/- 0.3 burst incidence mmHg-1 , P =
0.026) and cardiovagal BRS (9.5 +/- 1.4 vs. 23.6 +/- 4.3 ms mmHg-1 , P = 0.008)
were significantly blunted at rest. PTSD patients had significantly higher highly
sensitive-C-reactive protein levels compared to Controls (2.1 +/- 0.4 vs. 1.0 +/-
0.3 mg L-1 , P = 0.047). Augmented SNS and haemodynamic responses to mental
stress, blunted BRS and inflammation may contribute to an increased CV risk in
PTSD.
PMID- 28503729
TI - Fully integrated 3D high-resolution multicontrast abdominal PET-MR with high scan
efficiency.
AB - PURPOSE: To provide 3D multicontrast anatomical MR with high isotropic resolution
and metabolic positron emission tomography (PET) images using a respiratory
motion-compensated simultaneous PET-MR examination with high scan efficiency.
THEORY AND METHODS: Standard abdominal PET-MR examinations combine MR data
obtained during multiple breath-holds with free-breathing PET acquisitions,
limiting the achievable image resolution and potentially causing misalignment
errors between breath-hold and free-breathing data. Here, a 3D free-breathing PET
MR acquisition is presented, yielding T1 and T2 -weighted MR images with an
isotropic resolution of 1.5 mm3 . In addition, nonrigid respiratory motion
information and respiratory-resolved attenuation-correction maps are obtained
without an increase in scan time. Motion information is used in motion
compensated image reconstructions to improve MR and PET image quality while
shortening scan times. RESULTS: The proposed approach was evaluated in 11
oncology patients and provided respiratory motion information with an accuracy of
1.3 +/- 0.1 mm. Sharpness of anatomical features was increased by 19 +/- 13%
compared with the uncorrected MR images in a 54 +/- 26% shorter scan time than a
gated MR acquisition. The MR-based motion information improved uptake values (75
+/- 94%) and resolution (16 +/- 27%) of simultaneously acquired PET images.
CONCLUSIONS: The proposed method provides motion-compensated 3D high-quality MR
and PET images in a comprehensive and highly efficient examination. Magn Reson
Med 79:900-911, 2018. (c) 2017 International Society for Magnetic Resonance in
Medicine.
PMID- 28503730
TI - Cardiopulmonary and sedative effects of intravenous or epidural methadone in
conscious dogs.
AB - Cardiopulmonary and sedative effects of intravenous or epidural methadone were
compared. Six beagles were randomly assigned to group MIV (methadone 0.5 mg/kg IV
+ NaCl 0.9% epidurally) or MEP (methadone 0.5 mg/kg epidurally + NaCl 0.9% IV).
Cardiopulmonary, blood gas and sedation were assessed at time (T) 0, 15, 30, 60,
120, 240 and 480 min after drug administration. Compared to T0, heart rate
decreased at T15-T120 in MIV (p < .001) and T15-T240 in MEP (p < .05); mean
arterial pressure was reduced at T15-T60 in MEP (p < .01); respiratory rate was
higher at T15 and T30 in both groups (p < .05); pH was lower at T15-T120 in MIV
(p < .01) and T15, T30 and T120 in MEP (p < .05); PaCO2 was higher at T15-T60 in
MIV (p < .01) and T15, T30 and T120 in MEP (p < .01); sedation scores were higher
at T15 and T30 in MIV and T15-T60 in MEP (p < .05). At T120 and T240, sedation
score was higher in group MEP compared with group MIV (p < .01) In conclusion,
cardiopulmonary and sedative effects of identical methadone doses are similar
when administered IV or epidurally to conscious healthy dogs.
PMID- 28503731
TI - A Microfluidic Ion Pump for In Vivo Drug Delivery.
AB - Implantable devices offer an alternative to systemic delivery of drugs for the
treatment of neurological disorders. A microfluidic ion pump (uFIP), capable of
delivering a drug without the solvent through electrophoresis, is developed. The
device is characterized in vitro by delivering gamma-amino butyric acid to a
target solution, and demonstrates low-voltage operation, high drug-delivery
capacity, and high ON/OFF ratio. It is also demonstrated that the device is
suitable for cortical delivery in vivo by manipulating the local ion
concentration in an animal model and altering neural behavior. These results show
that uFIPs represent a significant step forward toward the development of
implantable drug-delivery systems.
PMID- 28503734
TI - Retropubic tissue fixation system tensioned mini-sling carried out under local
anesthesia cures stress urinary incontinence and intrinsic sphincter deficiency:
1-year data.
AB - OBJECTIVES: To assess the outcomes of the tissue fixation system midurethral
sling for the treatment of intrinsic sphincter deficiency. METHODS: We
retrospectively studied a total of 96 intrinsic sphincter deficiency patients
treated with the tissue fixation system midurethral sling at Yokohama Motomachi
Women's Clinic from 2006 to 2015. We evaluated intraoperative and 1-year
postoperative results. Regarding the cure rate, we divided patients into three
groups: (i) patients with maximum urethral closure pressure <20 and Valsalva leak
point pressure <65 combined (n = 17); (ii) patients with maximum urethral closure
pressure <20 (n = 55); and (iii) patients with Valsalva leak point pressure <65
(n = 47). RESULTS: The median age was 63 years (range 38-89 years). The median
operating time including local anesthesia was 24 min (range 12-55 min) and median
blood loss was 5.0 mL (range 3-69 mL). All operations were day surgery under
local anesthesia. Postoperative pain was minimal. All patients were discharged
the same day. There were no intraoperative complications except one bladder
perforation. There were no tape rejections. The 1-year postoperative cure rates
were: 88.2% among patients with maximum urethral closure pressure <20 and
Valsalva leak point pressure <65, 90.9% for patients with maximum urethral
closure pressure <20, and 85.1% among patients with Valsalva leak point pressure
<65. CONCLUSIONS: The tissue fixation system midurethral sling operation is a
simple, safe and effective operation for older women with intrinsic sphincter
deficiency, and it can be carried out under local anesthesia.
PMID- 28503732
TI - Imaging short-lived reactive oxygen species (ROS) with endogenous contrast MRI.
AB - PURPOSE: To characterize the relaxation properties of reactive oxygen species
(ROS) for the development of endogenous ROS contrast magnetic resonance imaging
(MRI). MATERIALS AND METHODS: ROS-producing phantoms and animal models were
imaged at 9.4T MRI to obtain T1 and T2 maps. Egg white samples treated with
varied concentrations of hydrogen peroxide (H2 O2 ) were used to evaluate the
effect of produced ROS in T1 and T2 for up to 4 hours. pH and temperature changes
due to H2 O2 treatment in egg white were also monitored. The influences from H2
O2 itself and oxygen were evaluated in bovine serum albumin (BSA) solution
producing no ROS. In addition, dynamic temporal changes of T1 in H2 O2 -treated
egg white samples were used to estimate ROS concentration over time and hence the
detection sensitivity of relaxation-based endogenous ROS MRI. The relaxivity of
ROS was compared with that of Gd-DTPA as a reference. Finally, the feasibility of
in vivo ROS MRI with T1 mapping acquired using an inversion recovery sequence was
demonstrated with a well-established rotenone-treated mouse model (n = 6).
RESULTS: pH and temperature changes in treated egg white samples were
insignificant (<0.1 unit and <1 degrees C, respectively). T1 relaxation time in
the H2 O2 -treated egg white was reduced significantly (P < 0.05), while there
was only small reduction in T2 (<10%). In the H2 O2 -treated BSA solution that
produce no ROS, there was a small change in T1 due to H2 O2 itself (+/-1%),
although a significant T2 -shortening effect was observed (>10%, P < 0.05). Also,
there was a small reduction in T1 (13 +/- 1%) and T2 (1 +/- 2%) from molecular
oxygen. The detection sensitivity of ROS MRI was estimated around 10 pM. The T1
relaxivity of ROS was found to be much higher than that of Gd-DTPA (3.4 * 107 vs.
0.9 s-1 .mM-1 ). Finally, significantly reduced T1 was observed in rotenone
treated mouse brain (5.1 +/- 2.5%, P < 0.05). CONCLUSION: We demonstrated in the
study that endogenous ROS MRI based on the paramagnetic effect has sensitivity
for in vitro and in vivo applications. LEVEL OF EVIDENCE: 2 Technical Efficacy
Stage: 2 J. Magn. Reson. Imaging 2018;47:222-229.
PMID- 28503733
TI - Long-term safety from transmission of porcine endogenous retrovirus after pig-to
non-human primate corneal transplantation.
AB - BACKGROUND: The risk of xenozoonosis mainly by porcine endogenous retrovirus
(PERV) has been considered as one of the main hurdles in xenotransplantation and
therefore should be elucidated prior to the clinical use of porcine corneal
grafts. Accordingly, an investigation was performed to analyze the infectivity of
PERVs from porcine keratocytes to human cells, and the long-term risk of
transmission of PERVs was determined using pig-to-non-human primate (NHP) corneal
transplantation models. METHODS: The infectivity of PERVs from the SNU miniature
pig keratocytes was investigated by coculture with a human embryonic kidney cell
line. Twenty-two rhesus macaques underwent xenocorneal transplantation as
follows: (i) group 1 (n=4): anterior lamellar keratoplasty (LKP) with freshly
preserved porcine corneas, (ii) group 2 (n=5): anterior LKP with decellularized
porcine corneas followed by penetrating keratoplasty (PKP) with allografts, (iii)
group 3 (n=3): PKP under steroid-based immunosuppression, (iv) group 4 (n=4): PKP
under anti-CD154 antibody-based immunosuppression, (v) group 5 (n=4): deep
anterior LKP with freshly preserved porcine corneas under anti-CD40 antibody
based immunosuppression, and (vi) group 6 (n=2): PKP under anti-CD40 antibody
based immunosuppression. Postoperative blood samples were serially collected, and
tissue samples were obtained from thirteen different organs at the end of each
experiment. The existence of PERV DNA and RNA was investigated using PCR and RT
PCR. RESULTS: Using two independent in vitro infectivity tests, neither PERV pol
nor pig mitochondrial cytochrome oxidase II was detected after 41 and 92 days of
coculture, respectively. After xenocorneal transplantation, a total of 257 serial
peripheral blood mononuclear cell samples, 34 serial plasma samples, and 282
tissue samples were obtained from the NHP recipients up to 1176 days post
transplantation. No PERV transmission was evident in any samples. CONCLUSIONS:
Within the limits of this study, there is no evidence to support any risk of PERV
transmission from porcine corneal tissues to NHP recipients, despite the
existence of PERV-expressing cells in porcine corneas.
PMID- 28503735
TI - WDR45B-related intellectual disability, spastic quadriplegia, epilepsy, and
cerebral hypoplasia: A consistent neurodevelopmental syndrome.
AB - The advancement in genomic sequencing has greatly improved the diagnostic yield
for neurodevelopmental disorders and led to the discovery of large number of
novel genes associated with these disorders. WDR45B has been identified as a
potential intellectual disability gene through genomic sequencing of 2 large
cohorts of affected individuals. In this report we present 6 individuals from 3
unrelated families with homozygous pathogenic variants in WDR45B: c.799C>T
(p.Q267*) in 1 family and c.673C>T (p.R225*) in 2 families. These individuals
shared a similar phenotype including profound development delay, early-onset
refractory epilepsy, progressive spastic quadriplegia and contractures, and brain
malformations. Neuroimaging showed ventriculomegaly, reduced cerebral white
matter volume, and thinning of cerebral gray matter. The consistency in the
phenotype strongly supports that WDR45B is associated with this disease.
PMID- 28503737
TI - Inducing Complexity in Intermetallics through Electron-Hole Matching: The
Structure of Fe14 Pd17 Al69.
AB - We illustrate how the crystal structure of Fe14 Pd17 Al69 provides an example of
an electron-hole matching approach to inducing frustration in intermetallic
systems. Its structure contains a framework based on IrAl2.75 , a binary compound
that closely adheres to the 18-n rule. Upon substituting the Ir with a mixture of
Fe and Pd, a competition arises between maintaining the overall ideal electron
concentration and accommodating the different structural preferences of the two
elements. A 2*2*2 supercell results, with Pd- and Fe-rich regions emerging. Just
as in the original IrAl2.75 phase, the electronic structure of Fe14 Pd17 Al69
exhibits a pseudogap at the Fermi energy arising from an 18-n bonding scheme. The
electron-hole matching approach's ability to combine structural complexity with
electronic pseudogaps offers an avenue to new phonon glass-electron crystal
materials.
PMID- 28503736
TI - Hydrogen sulfide pretreatment improves mitochondrial function in myocardial
hypertrophy via a SIRT3-dependent manner.
AB - BACKGROUND AND PURPOSE: Hydrogen sulfide (H2 S) is a gaseous signal molecule with
antioxidative properties. Sirtuin 3 (SIRT3) is closely associated with
mitochondrial function and oxidative stress. The study was to investigate whether
and how H2 S improved myocardial hypertrophy via a SIRT3-dependent manner.
EXPERIMENTAL APPROACH: Neonatal rat cardiomyocytes were pretreated with NaHS (50
MUM) for 4 h followed by angiotensin II (Ang II, 100 nM) for 24 h. SIRT3 was
silenced with siRNA technology. SIRT3 promoter activity and expression, cell
surface, hypertrophic gene mRNA expression, mitochondrial oxygen consumption rate
and membrane potential were measured. Male 129S1/SvImJ [wild-type (WT)] and SIRT3
knockout (KO) mice were injected with NaHS (50 MUmol.kg-1 .day-1 ; i.p.) followed
by transverse aortic constriction (TAC). Echocardiography, heart mass,
mitochondrial ultrastructure, volume and number, oxidative stress, mitochondria
fusion and fission-related protein expression were measured. KEY RESULTS: In
vitro, NaHS increased SIRT3 promoter activity and SIRT3 expression in Ang II
induced cardiomyocyte hypertrophy. SIRT3 silencing abolished the ability of NaHS
to reverse the Ang II-induced cardiomyocyte hypertrophy, mitochondrial function
impairment and permeability potential dysfunction, along with the decline in
FOXO3a and SOD2 expression. In vivo, after TAC. NaHS attenuated myocardial
hypertrophy, inhibited oxidative stress, improved mitochondrial ultrastructure,
suppressed mitochondrial volume but increased mitochondrial numbers, enhanced
OPA1, MFN1 and MFN2 expression but suppressed DRP1 and FIS1 expression in WT mice
but not in SIRT3 KO mice CONCLUSION AND IMPLICATIONS: NaHS improved mitochondrial
function and inhibited oxidative stress in myocardial hypertrophy in a SIRT3
dependent manner. LINKED ARTICLES: This article is part of a themed section on
Spotlight on Small Molecules in Cardiovascular Diseases. To view the other
articles in this section visit
http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.
PMID- 28503739
TI - The Bleeding on Brushing Index: a novel index in preventive dentistry.
AB - BACKGROUND: The aim of this study was to evaluate the suitability of a
dichotomous index, based on a special interdental brushing tool, to detect
initial pathological processes in interproximal areas. Furthermore, different
techniques of interdental hygiene were compared. METHODS: Participants (n = 108)
were instructed to clean their teeth using the Bass technique and were randomly
assigned to three groups according to the type of interdental cleaning used:
group A, use of interdental brushes; group B, no interdental hygiene (the control
group); and group C, use of dental floss. Approximal Plaque Index (API), Plaque
Index (PI), modified Sulcus Bleeding Index (mSBI) and the Bleeding on Brushing
Index (BOB) were measured at baseline, and after 2 (t1) and 4 (t2) weeks.
Statistical analysis was performed using the Wilcoxon test and the Mann-Whitney U
test. RESULTS: One-hundred and six participants completed the study. The BOB
decreased significantly in all groups (P < 0.001) with the most pronounced
reduction being recorded for group A (baseline: 49.3 +/- 23.0%; 4 weeks: 5.1 +/-
6.9%). Also, the mSBI (P < 0.001) decreased significantly in all groups during
the study. The API appeared to be less affected by the oral hygiene than other
indices. The highest correlation was observed between BOB and mSBI (r = 0.785, P
< 0.001). CONCLUSION: The BOB is a valuable complement for the existing array of
indices in preventive dentistry, and is able to detect potential pathological
processes in interproximal spaces. Additionally, this study suggests that
interdental hygiene with individually selected brushes is superior to flossing.
CLINICAL RELEVANCE: With the BOB, gingival inflammation can be demonstrated to
patients, which could increase compliance.
PMID- 28503738
TI - Targeting human telomeric G-quadruplex DNA with antitumour natural alkaloid
aristololactam-beta-D-glucoside and its comparison with daunomycin.
AB - Study on anticancer agents that act via stabilization of telomeric G-quadruplex
DNA has emerged as novel and exciting field for anticancer drug discovery. The
interaction of carbohydrate containing anticancer alkaloid aristololactam-beta-D
glucoside (ADG) with human telomeric G-quadruplex DNA sequence was characterized
by different biophysical techniques. The binding parameters were compared with
daunomycin (DAN), a well-known chemotherapeutic drug. The Scatchard binding
isotherms revealed noncooperative binding for both with the binding affinity
values of (1.01 +/- 0.05) * 106 and (1.78 +/- 0.18) * 106 M-1 for ADG and DAN,
respectively. Circular dichroism, ferrocyanide quenching study, anisotropy study,
thiazole orange displacement, optical melting, differential scanning calorimetry
study, and molecular docking study suggest significant stacking and stabilizing
efficiency of ADG with comparison to DAN. The energetics of the interaction for
ADG and DAN revealed that both reactions were predominantly entropy driven.
Negative heat capacity values were obtained from the temperature dependence of
the enthalpy change. The standard molar Gibbs energy change exhibited only
marginal alterations with temperature suggesting the occurrence of enthalpy
entropy compensation. These findings indicate that ADG can act as a stabilizer of
telomeric G-quadruplex DNA and thereby can be considered as a potential
telomerase inhibitor.
PMID- 28503741
TI - The effect of autologous activated platelet-rich plasma injection on female
pattern hair loss: A randomized placebo-controlled study.
AB - BACKGROUND: Hair is an essential part of a woman's appearance and attractiveness.
This is reflected in the predominantly psychological morbidity that can be
associated with female pattern hair loss. Platelet-rich plasma(PRP) has been used
in numerous fields of medicine. Recently, PRP has received growing attention as a
potential therapeutic tool for hair loss. OBJECTIVE: To evaluate the efficacy and
safety of autologous platelet-rich plasma in the treatment of female pattern hair
loss. MATERIALS AND METHODS: Thirty female patients with female pattern hair loss
were randomly assigned to receive autologous PRP injection into a selected area,
and another area was injected with normal saline as a placebo. Sessions were
performed weekly for a maximum total of four sessions. Patients were followed up
6 months after the end of last session. The outcome was assessed both
subjectively and objectively. RESULTS: There was a statistical significant
difference between PRP and placebo areas (P<.005) regarding both hair density and
hair thickness as measured by a folliscope. The hair pull test became negative in
PRP-injected areas in 25 patients (83%) with average number of three hairs.
Global pictures showed a significant improvement in hair volume and quality
together with a high overall patient satisfaction in PRP-injected sites, and
these results were maintained during the 6-month follow- up. CONCLUSION: Platelet
rich plasma injections can be regarded as an alternative for the treatment of
female pattern hair loss with minimal morbidity and a low cost-to-benefit ratio.
PMID- 28503740
TI - Weed interference with peppermint (Mentha x piperita L.) and spearmint (Mentha
spicata L.) crops under different herbicide treatments: effects on biomass and
essential oil yield.
AB - BACKGROUND: 'Minor crops' such as spearmint and peppermint are high added value
crops, despite the fact that their production area is comparably small worldwide.
The main limiting factor in mint commercial cultivation is weed competition.
Thus, field experiments were carried out to evaluate the effects of weed
interference on growth, biomass and essential oil yield in peppermint and
spearmint under different herbicide treatments. RESULTS: The application of
pendimethalin and oxyfluorfen provided better control of annual weeds resulting
in higher crop yield. Additionally, when treated with herbicides both crops were
more competitive against annual weeds in the second year than in the first year.
All pre-emergence herbicides increased biomass yield, since pendimethalin,
linuron and oxyfluorfen reduced the density of annual weeds by 71-92%, 63-74% and
86-95%, respectively. Weed interference and herbicide application had no effect
on essential oil content; however, a relatively strong impact on essential oil
production per cultivated area unit was observed, mainly due to the adverse
effect of weed interference on plant growth. CONCLUSION: Considering that
pendimethalin and oxyfluorfen were effective against annual weeds in both
spearmint and peppermint crops, these herbicides should be included in integrated
weed management systems for better weed management in mint crops. (c) 2017
Society of Chemical Industry.
PMID- 28503743
TI - Benchmarking the research track record and level of appointment of Australian
occupational therapy academics.
AB - BACKGROUND: Academic faculty are active contributors to the evidence base of the
profession. Little is known about the research productivity of Australian
occupational therapy academics. METHODS: A bibliographic analysis of Australian
occupational therapy faculty websites and corresponding Scopus citation database
profiles was conducted. A description of current research productivity benchmarks
and relationships with holding a doctorate, academic appointment level and
institutional characteristics were explored. RESULTS: The median H-index of
Clinical and Associate Lecturers was 0, 1 for Lecturers, 4 for Senior Lecturers,
7.5 for Associate Professors and 13 for Professors. The number of publications
and number of citing documents follows a Pareto tendency, where 20% of
researchers are responsible for around 80% of the research track record of
Australian occupational therapy academics. CONCLUSION: The findings provide a
benchmark for Australian occupational therapy faculty research track records and
associations with appointment levels. This benchmark differs across countries and
disciplines. The results raise considerations for enhancing the overall research
track record of occupational therapy academics.
PMID- 28503742
TI - The ERN1 transcription factor gene is a target of the CCaMK/CYCLOPS complex and
controls rhizobial infection in Lotus japonicus.
AB - Bacterial accommodation inside living plant cells is restricted to the nitrogen
fixing root nodule symbiosis. In many legumes, bacterial uptake is mediated via
tubular structures called infection threads (ITs). To identify plant genes
required for successful symbiotic infection, we screened an ethyl
methanesulfonate mutagenized population of Lotus japonicus for mutants defective
in IT formation and cloned the responsible gene, ERN1, encoding an AP2/ERF
transcription factor. We performed phenotypic analysis of two independent L.
japonicus mutant alleles and investigated the regulation of ERN1 via
transactivation and DNA-protein interaction assays. In ern1 mutant roots, nodule
primordia formed, but most remained uninfected and bacterial entry via ITs into
the root epidermis was abolished. Infected cortical nodule cells contained
bacteroids, but transcellular ITs were rarely observed. A subset exhibited
localized cell wall degradation and loss of cell integrity associated with
bacteroid spread into neighbouring cells and the apoplast. Functional promoter
studies revealed that CYCLOPS binds in a sequence-specific manner to a motif
within the ERN1 promoter and in combination with CCaMK positively regulates ERN1
transcription. We conclude that the activation of ERN1 by CCaMK/CYCLOPS complex
is an important step controlling IT-mediated bacterial progression into plant
cells.
PMID- 28503744
TI - Treatment using tadalafil for severe pre-eclampsia with fetal growth restriction.
AB - For severe pre-eclampsia (PE) with fetal growth restriction (FGR), the only
effective treatment is early delivery of the placenta. Clinicians are often
forced to end the pregnancy because of maternal indications. We report a case of
severe PE with FGR in which the PE was temporarily improved and pregnancy
successfully prolonged with tadalafil, a phosphodiesterase 5 inhibitor. A 35-year
old primigravid woman presented at 27 3/7 weeks of gestation with severe PE and
FGR. After commencing tadalafil administration, biochemical and angiogenic
markers improved. Thereafter, hypertension and proteinuria temporarily improved.
Importantly, the pregnancy was prolonged by 14 days after the initiation of
tadalafil administration. Tadalafil may be a novel treatment for severe PE with
FGR to prolong pregnancy.
PMID- 28503745
TI - Interactions Between phyB and PIF Proteins Alter Thermal Reversion Reactions in
vitro.
AB - The dynamic behavior of the plant red/far-red light photoreceptor phytochrome B
(phyB) has been elucidated in natural and synthetic systems. Red light switches
phyB from the inactive Pr state to the active Pfr state, a process that is
reversed by far-red light. Alongside light signals, phyB activity is constrained
by thermal reversion (that is prominent in the dark) and protein-protein
interactions between phyB, other phytochrome molecules, and, among others,
PHYTOCHROME INTERACTING FACTORs (PIFs). Requirements for phyB-PIF association
have been well studied and are central to light-regulated synthetic tools.
However, it is unknown whether PIF interactions influence transitions of phyB
between different conformers. Here, we show that the in vitro thermal reversion
of phyB involves multiple reactions. Thermal reversion of phyB in vitro is
inhibited by PIF6, and this effect is observed at all temperatures tested. We
analyzed our experimental data using a mathematical model containing multiple Pfr
conformers, in accordance with previous findings. Remarkably, each Pfr conformer
is differentially regulated by PIF6 and temperature. As a result, we speculate
that in vivo phytochrome signaling networks may require similar levels of
complexity to fine-tune responses to the external environment.
PMID- 28503746
TI - Application of Ultrasound Elastography for Chronic Allograft Dysfunction in
Kidney Transplantation.
AB - Interstitial fibrosis is the main characteristic of chronic allograft
dysfunction, which remains the key factor affecting long-term allograft survival
after kidney transplantation. Ultrasound elastography (UE), including real-time
elastography, transient elastography, and acoustic radiation force impulse, has
been applied widely in breast, thyroid, and liver diseases, especially in the
assessment of liver fibrosis. Recently, numerous studies have reported the
efficacy of UE methods in evaluating renal allograft fibrosis. This review aims
to investigate the clinical applications, limitations, and future roles of UE in
current clinical practice in light of changing management paradigms. In current
clinical practice, UE methods, especially transient elastographic measurement,
appear to be useful for ruling out fibrosis but do not have sufficient accuracy
to distinguish between various stages of allograft fibrosis. Moreover, there
remain considerable issues to be solved for the application of UE in kidney
transplantation. Thus, UE methods cannot replace the crucial role of renal
allograft biopsy in the diagnosis and evaluation of allograft fibrosis in kidney
transplantation. Perhaps UE methods could be of more importance in the long-term
observation and evaluation of allograft fibrosis during follow-up.
PMID- 28503747
TI - Friends and family: A software program for identification of unrelated
individuals from molecular marker data.
AB - The identification of related and unrelated individuals from molecular marker
data is often difficult, particularly when no pedigree information is available
and the data set is large. High levels of relatedness or inbreeding can influence
genotype frequencies and thus genetic marker evaluation, as well as the accurate
inference of hidden genetic structure. Identification of related and unrelated
individuals is also important in breeding programmes, to inform decisions about
breeding pairs and translocations. We present Friends and Family, a Windows
executable program with a graphical user interface that identifies unrelated
individuals from a pairwise relatedness matrix or table generated in programs
such as coancestry and genalex. Friends and Family outputs a list of samples that
are all unrelated to each other, based on a user-defined relatedness cut-off
value. This unrelated data set can be used in downstream analyses, such as marker
evaluation or inference of genetic structure. The results can be compared to that
of the full data set to determine the effect related individuals have on the
analyses. We demonstrate one of the applications of the program: how the removal
of related individuals altered the Hardy-Weinberg equilibrium test outcome for
microsatellite markers in an empirical data set. Friends and Family can be
obtained from https://github.com/DeondeJager/Friends-and-Family.
PMID- 28503748
TI - Cigarette smoking induces only marginal changes in sperm DNA methylation levels
of patients undergoing intracytoplasmic sperm injection treatment.
AB - DNA methylation plays important roles in genome stability and regulation of gene
expression. This study was designed to determine the influence of cigarette
smoking on sperm DNA methylation. From a genome-wide survey on sperm samples,
differentially methylated target CpGs should be selected and subjected to local
deep bisulphite sequencing. Obtained methylation data are compared to sperm
parameters and (ICSI) outcome. Similar to pilot study, samples were subjected to
Infinium 450K BeadChip arrays to identify alterations in sperm DNA methylation
between smokers and nonsmokers males. Routine testing on a significantly altered
CpG site was performed on more samples using local deep bisulphite sequencing. Of
approximately 485,000 CpG sites analysed, only seven CpGs were found to show a
significant DNA methylation difference of >20% with the top six CpGs overlapping
common SNP sites. The remaining CpG site (cg19455396) is located in intron 12 of
the TAP2 gene. The results of deep bisulphite sequencing showed only a tendency
towards hypomethylation in the smoking group. This study could not detect
biologically relevant CpG positions that are altered in sperm DNA methylation on
the influence of cigarette smoking beyond individual-specific effects that may be
caused by other environmental factors.
PMID- 28503749
TI - A Prospective Evaluation of Transverse Tracheal Sonography During Emergent
Intubation by Emergency Medicine Resident Physicians.
AB - OBJECTIVES: Establishing a definitive airway is often the first step in emergency
department treatment of critically ill patients. Currently, there is no agreed
upon consensus as to the most efficacious method of airway confirmation. Our
objective was to determine the diagnostic accuracy of real-time sonography
performed by resident physicians to confirm placement of the endotracheal tube
during emergent intubation. METHODS: We performed a prospective cohort study of
adult patients in the emergency department undergoing emergent endotracheal
intubation. Thirty emergency medicine residents, who were blinded to end-tidal
carbon dioxide detection results, performed real-time transverse tracheal
sonography during intubation to evaluate correct endotracheal tube placement.
RESULTS: Seventy-two patients were enrolled in the study. Sixty-eight instances
(94.4%) were interpreted as correct placement in the trachea; 4 (5.6%) were
interpreted as esophageal, of which 1 was a false-negative finding, therefore
conferring sensitivity of 98.5% (95% confidence interval, 92.1%-99.9%) and
specificity of 75.0% (95% confidence interval, 19.4%-99.4%) for correct
placement. There was no significant difference in accuracy among resident
sonographers with different levels of residency training. CONCLUSIONS: A simple
transverse tracheal sonographic examination performed by emergency medicine
resident physicians can be used as an adjunct to help confirm correct
endotracheal tube placement during intubation. In our cohort, the level of
training did not appear to affect the ability of residents to correctly identify
the endotracheal tube position.
PMID- 28503750
TI - Comparative effects of liraglutide 3 mg vs structured lifestyle modification on
body weight, liver fat and liver function in obese patients with non-alcoholic
fatty liver disease: A pilot randomized trial.
AB - We compared the effects of weight loss induced by the glucagon-like peptide 1
agonist liraglutide with a structured lifestyle intervention in obese adults with
non-alcoholic fatty liver disease (NAFLD). Obese (body mass index >=30 kg/m2 ,
mean weight 96.0 +/- 16.3 kg) non-diabetic Asian adults, with NAFLD diagnosed by
liver fat fraction (LFF) >= 5.5% on magnetic resonance imaging without other
causes of hepatic steatosis, were randomized to a supervised program of dieting
(restriction by 400 kilocalories/d) plus moderate-intensity aerobic exercise
(~200 min/wk; DE group, n = 12), or liraglutide at the 3 mg daily dose approved
for weight loss (LI group, n = 12), for 26 weeks. Both DE and LI groups had
significant (P < .01) and similar reductions in weight (-3.5 +/- 3.3 vs -3.5 +/-
2.1 kg, respectively, P = .72), LFF (-8.9 +/- 13.4 vs -7.2% +/- 7.1%, P = .70),
serum alanine aminotransferase (-42 +/- 46 vs -34 +/- 27 U/L, P = .52) and
aspartate aminotransferase (-23 +/- 24 vs -18 +/- 15 U/L, P = .53). In this first
randomized study comparing the 2 weight-loss modalities for improving NAFLD,
liraglutide was as effective as structured lifestyle modification.
PMID- 28503751
TI - In vitro evaluation of potential transporter-mediated drug interactions of
evogliptin.
AB - To date, little is known about the transporter-mediated drug-drug interaction
(DDI) potential of evogliptin, a novel DPP-4 inhibitor. The objective of this
study was to evaluate the DDI potential of evogliptin using various in vitro
assays in transporter-expressing cell lines. After incubating evogliptin with
cells overexpressing OAT1, OAT3, OCT2, OATP1B1 and OATP1B3, there was no notable
cellular accumulation of evogliptin (fold accumulation, 0.41-1.86). In
bidirectional transport assays using a Caco-2 cell monolayer, a high efflux ratio
(ER, 522) of evogliptin was observed, which was significantly decreased (97.96%)
in the presence of a potent P-gp inhibitor. In assays using MDCKII-BCRP cell
monolayers, by contrast, a low net ER (1.16-1.26) was found. In similar cellular
uptake and bidirectional studies with probe substrates of P-gp, BCRP, OAT1, OAT3,
OCT2, OATP1B1 and OATP1B3, the active transport of the substrates was not
significantly suppressed by evogliptin. These results suggest that evogliptin may
be a substrate of P-gp, but not a substrate of BCRP, OAT1B1, OAT1B3, OAT1, OAT3
or OCT2, and not an inhibitor of any of these transporters. Therefore, it could
be concluded that evogliptin has some DDI potential involving P-gp, but it has
low potential of DDI mediated by the other transporters.
PMID- 28503752
TI - Point-of-Care Diagnosis of Cardiac Tamponade Identified by the Flow Velocity
Paradoxus.
AB - The presentation of cardiac tamponade is a spectrum from occult to extreme. The
clinical history, physical exam, electrocardiogram, and radiographic findings of
tamponade have poor sensitivities and even worse specificities. We use a clinical
scenario to demonstrate how point-of-care cardiac ultrasound can diagnose
impending cardiac tamponade in a clinically stable patient. The ultrasound
finding we recommend is the flow velocity paradoxus, in which respiratory
variation causes significant changes in transvalvular inflow velocities, which
are exaggerated when tamponade is present. The management of a pericardial
effusion depends on its physiologic effect, and point-of-care ultrasound directly
measures that effect and expedites patient care.
PMID- 28503753
TI - Distal Forearm Fracture Open Reduction-Internal Fixation: Sonographic Detection
of Hardware Malalignment and Associated Tendon Injuries Missed by Radiography.
AB - Tendon injury is a known complication of distal radius fracture plate and screw
fixation. Targeted musculoskeletal sonography is uniquely capable of assessing
both tendon integrity and hardware abnormalities not recognized on radiographs.
Each of the 3 patients described presented with pain after an open reduction
internal fixation following a distal forearm fracture. In each patient,
radiographic findings, specifically the hardware position, were interpreted as
normal. Important radiographically occult observations were subsequently made
with sonography, including 3 proud screws and tendon injuries, all of which
required surgical treatment. This case series demonstrates the clinical utility
of musculoskeletal sonography in symptomatic patients after distal radius open
reduction-internal fixation with negative radiographic findings. In our practice,
sonography has been the most useful modality for precluding missing or delaying
the diagnosis and treatment of these hardware complications. We advocate its use
as an adjunct in any department performing musculoskeletal imaging.
PMID- 28503754
TI - An unusual pathological posterior vitreous detachment.
PMID- 28503755
TI - Wanting to work: managing the sick role in high-stake sickness insurance
meetings.
AB - This article respecifies and develops Parsons's sick role theory, focusing on the
postulate that the sick person must 'want' to get well. Using conversation
analysis and discursive psychology to study how the psychological term 'want' is
used in high-stake, multi-professional meetings with sickness benefit claimants
in Sweden, the article shows how establishing that one 'wants' to get well
requires extensive interactional work. In the examined meetings, the sick
person's 'want' formulations make explicit the relationship between 'wants' and
illness or inabilities, thus allowing for motivational character to be
established without committing to its implications, and without appearing
strategic or biased. By contrast, professional parties in the meetings invoke the
sick person's 'wants' either to hold them accountable, or for establishing a
desired course of recovery, confirming the centrality of such 'wants' in this
setting as well as the risks associated with expressing them. The article
suggests that analysing psychological matters as they are oriented to by
participants renders sick role theory relevant for a wide range of settings and
respecifies criticism of the model.
PMID- 28503756
TI - Biofilms and delayed healing - an in vitro evaluation of silver- and iodine
containing dressings and their effect on bacterial and human cells.
AB - This study investigated whether there are differences in the ability of wound
dressings to modulate certain factors known to affect wound healing. A selection
of antimicrobial dressings (AQUACEL(r) Ag ExtraTM , AQUACEL(r) Ag+ ExtraTM ,
IODOFLEXTM , ACTICOATTM 7 and PROMOGRAN PRISMATM matrix) were tested for their
effect on both bacterial bioburden and human dermal fibroblasts. Some dressings
underwent further evaluation for activity against Pseudomonas aeruginosa biofilms
using a colony-drip flow reactor model. The ability of in vitro biofilms to
produce proteases, and the effect of PROMOGRAN PRISMA matrix on such proteases,
was also investigated. All antimicrobial dressings tested reduced vegetative
bacterial load; however, only PROMOGRAN PRISMA matrix was able to significantly
reduce biofilm populations (P = 0.01). Additionally, PROMOGRAN PRISMA matrix was
the only dressing that did not inhibit dermal fibroblast growth. All other
dressings were detrimental to cell viability. In vitro biofilms of Pseudomonas
aeruginosa were demonstrated as being capable of releasing bacterial proteases
into their surroundings, and incubation with PROMOGRAN PRISMA matrix led to a 77%
reduction in activity of such proteases (P = 0.002). The unique ability of
PROMOGRAN PRISMA matrix to reduce in vitro vegetative bacteria, biofilm bacteria
and bacterial proteases while still allowing dermal fibroblast proliferation may
help rebalance the wound environment and reduce the occurrence of infection.
PMID- 28503757
TI - Increase in minimal erythemal dose following oral administration of an
antioxidant complex based on a mix of carotenoids: Double-blind, placebo
controlled trial.
PMID- 28503758
TI - Postnatal mandible growth in wild and laboratory mice: Differences revealed from
bone remodeling patterns and geometric morphometrics.
AB - Comparative information on the variation in the temporospatial patterning of
mandible growth in wild and laboratory mice during early postnatal ontogeny is
scarce but important to understand variation among wild rodent populations. Here,
we compare mandible growth between two ontogenetic series from the second to the
eighth week of postnatal life, corresponding to two different groups of mice
reared under the same conditions: the classical inbred strain C57BL/6J, and Mus
musculus domesticus. We characterize the ontogenetic patterns of bone remodeling
of the mandibles belonging to these laboratory and wild mice by analyzing bone
surface, as well as examine their ontogenetic form changes and bimodular
organization using geometric morphometrics. Through ontogeny, the two mouse
groups display similar directions of mandible growth, according to the
temporospatial distribution of bone remodeling fields. The allometric shape
variation of the mandibles of these mice entails the relative enlargement of the
ascending ramus. The organization of the mandible into two modules is confirmed
in both groups during the last postnatal weeks. However, especially after
weaning, the mandibles of wild and laboratory mice differ in the timing and
localization of several remodeling fields, in addition to exhibiting different
patterns of shape variation and differences in size. The stimulation of dentary
bone growth derived from the harder post-weaning diet might account for some
features of postnatal mandible growth common to both groups. Nonetheless, a large
component of the postnatal growth of the mouse mandible appears to be driven by
the inherent genetic programs, which might explain between-group differences.
PMID- 28503759
TI - Evaluation of Weight Change During Carboplatin Therapy in Dogs With Appendicular
Osteosarcoma.
AB - BACKGROUND: The prevalence of cancer cachexia in veterinary medicine has not been
studied widely, and as of yet, no definitive diagnostic criteria effectively
assess this syndrome in veterinary patients. OBJECTIVES: (1) To determine the
patterns of weight change in dogs with appendicular osteosarcoma treated with
amputation and single-agent carboplatin during the course of adjuvant
chemotherapy; and (2) to determine whether postoperative weight change is a
negative prognostic indicator for survival time in dogs with osteosarcoma.
ANIMALS: Eighty-eight dogs diagnosed with appendicular osteosarcoma. Animals were
accrued from 3 veterinary teaching hospitals. METHODS: Retrospective, multi
institutional study. Dogs diagnosed with appendicular osteosarcoma and treated
with limb amputation followed by a minimum of 4 doses of single-agent carboplatin
were included. Data analyzed in each patient included signalment, tumor site,
preoperative serum alkaline phosphatase activity (ALP), and body weight (kg) at
each carboplatin treatment. RESULTS: A slight increase in weight occurred over
the course of chemotherapy, but this change was not statistically significant.
Weight change did not have a significant effect on survival. Institution, patient
sex, and serum ALP activity did not have a significant effect on survival.
CONCLUSIONS AND CLINICAL IMPORTANCE: Weight change was not a prognostic factor in
these dogs, and weight loss alone may not be a suitable method of determining
cancer cachexia in dogs with appendicular osteosarcoma.
PMID- 28503760
TI - The penetrance of paraganglioma and pheochromocytoma in SDHB germline mutation
carriers.
AB - Germline mutations in succinate dehydrogenase B (SDHB) predispose to hereditary
paraganglioma (PGL) syndrome type 4. The risk of developing PGL or
pheochromocytoma (PHEO) in SDHB mutation carriers is subject of recent debate. In
the present nationwide cohort study of SDHB mutation carriers identified by the
clinical genetics centers of the Netherlands, we have calculated the penetrance
of SDHB associated tumors using a novel maximum likelihood estimator. This
estimator addresses ascertainment bias and missing data on pedigree size and
structure. A total of 195 SDHB mutation carriers were included, carrying 27
different SDHB mutations. The 2 most prevalent SDHB mutations were Dutch founder
mutations: a deletion in exon 3 (31% of mutation carriers) and the c.423+1G>A
mutation (24% of mutation carriers). One hundred and twelve carriers (57%)
displayed no physical, radiological or biochemical evidence of PGL or PHEO. Fifty
four patients had a head and neck PGL (28%), 4 patients had a PHEO (2%), 26
patients an extra-adrenal PGL (13%). The overall penetrance of SDHB mutations is
estimated to be 21% at age 50 and 42% at age 70 when adequately corrected for
ascertainment. These estimates are lower than previously reported penetrance
estimates of SDHB-linked cohorts. Similar disease risks are found for different
SDHB germline mutations as well as for male and female SDHB mutation carriers.
PMID- 28503761
TI - Diabetes among Maori women with self-reported past gestational diabetes mellitus
in a New Zealand Maori community.
AB - BACKGROUND: Gestational diabetes mellitus (GDM) is a risk factor for subsequent
development of type 2 diabetes mellitus (T2DM). We have investigated the extent
of this risk among Maori women without known diabetes. MATERIALS AND METHODS: We
recruited 2786 Maori women aged 28-86 years between 2004 and 2006, without
diagnosed diabetes from the Waikato and Southern Lakes regions, via media,
community and general practitioner channels, and invited them for an oral glucose
tolerance test (OGTT). RESULTS: Fifty (1.8%) women reported previous GDM (pGDM).
The prevalence decreased significantly with age (P = 0.009). Women aged <50 years
with pGDM had higher body mass index (35.6 +/- 6.7 vs 32.4 +/- 7.7 kg/m2 , P <
0.01), waist circumference (105.3 +/- 18.8 vs 96.9 +/- 16.6 cm, P < 0.01),
fasting blood glucose (5.5 +/- 1.0 vs 5.1 +/- 0.8 mmol/L, P <= 0.01), two-hour
post-prandial blood glucose (6.6 +/- 3.0 vs 5.6 +/- 2.1 mmol/L, P < 0.01) and
HbA1c (6.0 +/- 0.8 vs 5.8 +/- 0.6%, P < 0.05) than women without pGDM. PGDM was a
significant risk factor for undiagnosed diabetes (odds ratio 4.0; (5% confidence
interval 1.67-9.71). Undiagnosed diabetes was significantly more prevalent among
women with than without pGDM aged <40 years (20.0% vs 1.5%). CONCLUSION: Self
reported past GDM was a significant risk factor for undiagnosed diabetes in this
Maori population, particularly among women aged <40 years, highlighting the
importance of targeting this group for more intensive screening.
PMID- 28503762
TI - Contribution to the discussion of "A critical evaluation of the current 'p-value
controversy'".
PMID- 28503763
TI - Visible Light Induced Organic Transformations Using Metal-Organic-Frameworks
(MOFs).
AB - With the aim of developing renewable energy based processes, researchers are
paying increasing interest to light induced organic transformations. Metal
organic frameworks (MOFs), a class of micro-/mesoporous hybrid materials, are
recently emerging as a new type of photoactive materials for organic syntheses
due to their unique structural characteristics. In this Review, we summarized the
recent applications of MOFs as photocatalysts for light induced organic
transformations, including (1) oxidation of alcohols, amines, alkene, alkanes and
sulfides; (2) hydroxylation of aromatic compounds like benzene; (3) activation of
the C-H bonds to construct new C-C or C-X bonds; (4) atom-transfer radical
polymerization (ATRP). This Review starts with general background information of
using MOFs in photocatalysis, followed by a description of light induced organic
transformations promoted by photoactive inorganic nodes and photocatalytic active
ligands in MOFs, respectively. Thereafter, the use of MOFs as multifunctional
catalysts for light induced organic transformations via an efficient merge of the
metal/ligand/guest based catalysis where the photocatalytic activity of MOFs
plays a key role are discussed. Finally, the limitations, challenges and the
future perspective of the application of MOFs for light induced organic
transformations were addressed. The objective of this Review is to serve as a
starting point for other researchers to get into this largely unexplored field.
It is also our goal to stimulate intensive research in this field for rational
designing of MOF materials to overcome their current limitations in
photocatalysis, which can lead to more creative visible-light-induced organic
transformations.
PMID- 28503765
TI - 57th Annual Teratology Society Meeting.
PMID- 28503764
TI - Interpretation of Seemingly Contradictory Data: Low NMR S2 Order Parameters
Observed in Helices and High NMR S2 Order Parameters in Disordered Loops of the
Protein hGH at Low pH.
AB - At low pH, human growth hormone (hGH) adopts a partially folded state, in which
the native helices are maintained, but the long loop regions and side-chain
packing become disordered. Some of the S2 order parameters for backbone N-H
vectors derived from NMR relaxation measurements on hGH at low pH initially seem
contradictory. Three isolated residues (15, 20, and 171) in helices A and D
exhibit low order parameter values (<0.5) indicating flexibility, whereas residue
143 in the centre of a long flexible loop region has a high order parameter
(0.82). Using S2 order parameter restraining MD simulations, this paradox has
been resolved. Low S2 values in helices are due to the presence of a mixture of
310 -helical and alpha-helical hydrogen bonds. High S2 values in relatively
disordered parts of a protein may be due to fluctuating networks of hydrogen
bonds between the backbone and the side chains, which restrict the motion of N-H
bond vectors.
PMID- 28503766
TI - Editorial Comment to Pelvic floor muscle therapy or alpha-blocking agents for
treatment of men with lower urinary tract symptoms: An exploratory randomized
controlled trial.
PMID- 28503767
TI - The world of epithelial sheets.
AB - An epithelium is a layer of closely connected cells covering the body or lining a
body cavity. In this review, several fundamental questions are addressed
regarding the epithelium. (i) While an epithelium functions as barrier against
the external environment, how is barrier function maintained during its
construction? (ii) What determines the apical and basal sides of epithelial
layer? (iii) Is there any relationship between the apical side of the epithelium
and the apical membrane of an epithelial cell? (iv) Why are hepatocytes (liver
cells) called epithelial, even though they differ completely from column-like
shape of typical epithelial cells? Keeping these questions in mind, multiple
shapes of epithelia were considered, extracting a few of their elemental
processes, and constructing a virtual world of epithelia by combining them.
Epithelial cells were also classified into several types based on the number of
apical domains of each cell. In addition, an intracellular organelle was
introduced within epithelial cells, the vacuolar apical compartment (VAC), which
is produced within epithelial cells surrounded by external cell matrix (ECM). The
VAC interacts with areas of cell-cell contact of the cell surface membrane and is
converted to apical membrane. The properties of VACs enable us to answer the
initial questions posed above. Finally, the genetic and molecular mechanisms of
epithelial morphogenesis are discussed.
PMID- 28503768
TI - Contribution of cardiometabolic risk factors to estimated glomerular filtration
rate decline in Indigenous Australians with and without albuminuria - the eGFR
Follow-up Study.
AB - AIM: We assessed associations between cardiometabolic risk factors and estimated
glomerular filtration rate (eGFR) decline according to baseline albuminuria to
identify potential treatment targets in Indigenous Australians. METHODS: The eGFR
Follow-up Study is a longitudinal cohort of 520 Indigenous Australians. Linear
regression was used to estimate associations between baseline cardiometabolic
risk factors and annual Chronic Kidney Disease Epidemiology Collaboration eGFR
change (mL/min per 1.73m2 /year), among those classified with baseline
normoalbuminuria (urine albumin-to-creatinine ratio (uACR) <3 mg/mmol; n = 297),
microalbuminuria (uACR 3-30 mg/mmol; n = 114) and macroalbuminuria (uACR >=30
mg/mmol; n = 109). RESULTS: After a median of 3 years follow-up, progressive
declines of the age- and sex-adjusted mean eGFR were observed across albuminuria
categories (-2.0 [-2.6 to -1.4], -2.5 [-3.7 to -1.3] and -6.3 [-7.8 to -4.9]
mL/min per 1.72m2 /year). Although a borderline association was observed between
greater baseline haemoglobin A1c and eGFR decline in those with macroalbuminuria
(P = 0.059), relationships were not significant in those with microalbuminuria (P
= 0.187) or normoalbuminuria (P = 0.23). Greater baseline blood pressure, C
reactive protein, waist-to-hip ratio and lower high-density lipoprotein
cholesterol showed non-significant trends with greater eGFR decline in the
presence of albuminuria. CONCLUSION: Over a 3 year period, marked eGFR decline
was observed with greater baseline albuminuria. Cardiometabolic risk factors were
not strong predictors for eGFR decline in Indigenous Australians without
albuminuria. Longer follow-up may elucidate the role of these predictors and
other mechanisms in chronic kidney disease progression in this population.
PMID- 28503771
TI - Editorial Comment from Dr Campobasso to Adult genitourinary sarcoma: Clinical
characteristics and survival in a series of patients treated at a high-volume
institution.
PMID- 28503770
TI - Disposition of levetiracetam in healthy adult horses.
AB - Nine horses received 20 mg/kg of intravenous (LEVIV ); 30 mg/kg of intragastric,
crushed immediate release (LEVCIR ); and 30 mg/kg of intragastric, crushed
extended release (LEVCER ) levetiracetam, in a three-way randomized crossover
design. Crushed tablets were dissolved in water and administered by nasogastric
tube. Serum samples were collected over 48 hr, and levetiracetam concentrations
were determined by immunoassay. Mean +/- SD peak concentrations for LEVCIR and
LEVCER were 50.72 +/- 10.60 and 53.58 +/- 15.94 MUg/ml, respectively. The y
intercept for IV administration was 64.54 +/- 24.99 MUg/ml. The terminal half
life was 6.38 +/- 1.97, 7.07 +/- 1.93 and 6.22 +/- 1.35 hr for LEVCIR , LEVCER,
and LEVIV , respectively. Volume of distribution at steady-state was 630 +/- 73.4
ml/kg. Total body clearance after IV administration was 74.40 +/- 19.20 ml kg-1
hr-1 . Bioavailability was 96 +/- 10, and 98 +/- 13% for LEVCIR and LEVCER ,
respectively. A single dose of Levetiracetam (LEV) was well tolerated. Based on
this study, a recommended dosing regimen of intravenous or oral LEV of 32 mg/kg
every 12 hr is likely to achieve and maintain plasma concentrations within the
therapeutic range suggested for humans, with optimal kinetics throughout the
dosing interval in healthy adult horses. Repeated dosing and pharmacodynamic
studies are warranted.
PMID- 28503772
TI - Refractory thoracic endometriosis syndrome with bilateral hemothorax.
AB - Thoracic endometriosis syndrome (TES) is a rare disorder presenting with
catamenial pneumothorax, hemothorax, hemoptysis or pulmonary nodules. Bilateral
involvement is uncommon, and only a very few cases have been reported in the
literature. We report a case of bilateral catamenial hemothorax in a patient with
recurrent thoracic endometriosis. Despite multiple surgical interventions, the
patient continued to develop hemopneumothorax coinciding with menses. Remission
was finally achieved with the addition of gonadotropin-releasing hormone agonist,
highlighting the effectiveness of postoperative adjuvant hormone therapy and
supporting a combined surgical and medical approach in the treatment of TES in
patients who desire future fertility.
PMID- 28503769
TI - Identification of factors required for m6 A mRNA methylation in Arabidopsis
reveals a role for the conserved E3 ubiquitin ligase HAKAI.
AB - N6-adenosine methylation (m6 A) of mRNA is an essential process in most
eukaryotes, but its role and the status of factors accompanying this modification
are still poorly understood. Using combined methods of genetics, proteomics and
RNA biochemistry, we identified a core set of mRNA m6 A writer proteins in
Arabidopsis thaliana. The components required for m6 A in Arabidopsis included
MTA, MTB, FIP37, VIRILIZER and the E3 ubiquitin ligase HAKAI. Downregulation of
these proteins led to reduced relative m6 A levels and shared pleiotropic
phenotypes, which included aberrant vascular formation in the root, indicating
that correct m6 A methylation plays a role in developmental decisions during
pattern formation. The conservation of these proteins amongst eukaryotes and the
demonstration of a role in writing m6 A for the E3 ubiquitin ligase HAKAI is
likely to be of considerable relevance beyond the plant sciences.
PMID- 28503773
TI - The table grape 'Victoria' with a long shaped berry: a potential mutation with
attractive characteristics for consumers.
AB - BACKGROUND: Puglia is the most important region in Italy for table grape
production. Since consumers look for new products, the number of table grape
varieties has greatly increased in recent years. RESULTS: In a survey in the
Puglia region, we identified several years ago a potential mutation of the cv.
Victoria. We described this accession in comparison with the standard Victoria
for some amphelographic traits. All the characteristics were very similar to the
standard Victoria except for the berry shape, which was significantly more
elongated. Moreover, the berry of the mutated Victoria showed higher firmness,
lightness and chroma than the standard one, with a more intense yellow colour of
the skin (appreciated by consumers). The molecular characterisation with 25 SSR
markers showed that normal and mutant Victoria were genetically identical at all
the analysed loci, thus suggesting that the two accessions could be considered as
clones with the difference in berry shape probably due to a somatic mutation.
CONCLUSIONS: This mutation of the cv. Victoria may have interesting perspective
for the market since consumers are always attracted by different shape and colour
of the fruits (consumers buy with eyes). This accession can be an alternative
clone of the already known standard Victoria. (c) 2017 Society of Chemical
Industry.
PMID- 28503774
TI - Effect of the injectable contraceptive depot-medroxyprogesterone acetate on
coagulation parameters in new users.
AB - AIM: The aim of this study was to assess the effects of the injectable depot
medroxyprogesterone acetate (DMPA) contraceptive on selected blood coagulation
parameters in young, healthy new users. METHODS: The prospective study included
39 healthy women aged 20-39 years, with a body mass index (BMI; kg/m2 ) < 30, who
were never users of DMPA, and who opted to use DMPA (21 women) or a copper
intrauterine device (IUD; 18 women). The women in the two groups were matched for
age (+/-1 year) and BMI (+/-1). Blood samples were obtained from all participants
at baseline and at 6 and 12 months. Activated partial thromboplastin time, D
dimer, protein C, antithrombin, protein S, and thrombin generation test (lag
time, endogenous thrombin potential, time to peak, and velocity index of thrombin
generation) were analyzed. Repeated-measures analysis of variance was used to
compare the groups. RESULTS: There were no significant differences between the
groups at baseline with respect to any of the parameters evaluated; however, in
the DMPA group, D-dimer levels were lower and the time to peak thrombin
generation was longer than in the IUD group at 12 months of evaluation.
CONCLUSION: Lower D-dimer and longer time to peak thrombin generation in new
users of DMPA suggest a positive profile against hypercoagulability.
PMID- 28503775
TI - Contemporary psychology and women: A gender analysis of the scientific
production.
AB - Despite important advances made in recent decades, women are still
underrepresented in science (less than 30% of authorships). This study presents a
bibliometric analysis of all the Psychology articles published in 2009 included
in the Web of Science database (Thomson Reuters) in order to examine the
contribution of women in contemporary Psychology, their pattern of research
collaboration, the scientific content and the scientific impact from a gender
perspective. From a total of 90,067 authorships, gender could be identified in
74,413 (82.6%) of them, being 40,782 (54.8%) male authorships and 33,631 (45.2%)
female authorships. These data corresponded to 24,477 (49.9%) individual men and
24,553 (50.1%) women, respectively. Therefore, Psychology presents gender parity
in the number of authors, and a gender asymmetry in the number of authorships
that it is much lower than in science in general and other specific scientific
fields. In relative terms, women tend to be concentrated in the first position of
the authorship by-line and much less in the last (senior) position. This double
pattern suggests that age probably plays a role in (partly) explaining the slight
gender disparity of authorships.
PMID- 28503776
TI - Differences in dietary and lifestyle habits between pregnant women with small
fetuses and appropriate-for-gestational-age fetuses.
AB - AIM: The purpose of this study was to determine differences in lifestyle and
dietary habits between pregnant women with small for gestational age (SGA)
fetuses and those appropriate for gestational age (AGA). METHODS: This cross
sectional, prospective study was conducted over 14 months and included 46 mothers
with SGA and 81 with AGA fetuses. Fetal growth was assessed by a routine third
trimester scan. Participants completed questionnaires regarding dietary habits,
lifestyle behavior and sociodemographic characteristics during the third
trimester. RESULTS: Mothers maintaining a Mediterranean-type diet and lifestyle
were more likely to have an AGA fetus (P < 0.05). The same number of women in
both groups ate a vegetarian diet. Women in the SGA group had a lower intake of
certain micronutrients: carotene, folic acid, iron, potassium and magnesium (P <
0.05). Women in the AGA group ate more vegetables, especially green beans,
carrots, lettuce and oranges (P < 0.05). Bread, pasta, cakes and jam were also
more frequently consumed by the AGA group (P < 0.05). Mothers in the SGA group
drank more cola (P < 0.05), while mothers in the AGA group drank more diet cola
and wine (P < 0.05). Women in the SGA group smoked more cigarettes per day (P <
0.05). CONCLUSIONS: Mothers of SGA fetuses had a different nutritional intake and
cigarette smoking habits compared with mothers of AGA fetuses. No other
differentiating lifestyle habits were observed between the groups. Thus,
intrauterine growth conditions might be improved by the endorsement of certain
dietary habits during pregnancy.
PMID- 28503777
TI - Determination of threshold concentrations of plant pollens in intradermal testing
using fluorescein in clinically healthy nonallergic cats.
AB - BACKGROUND: Currently the same allergen concentrations for canine intradermal
testing (IDT) are recommended for feline IDT. Feline skin reactions are subtle
and more difficult to read than canine reactions. This difference may be due to
suboptimal allergen concentrations used for IDT in cats. HYPOTHESIS/OBJECTIVES:
To determine the irritant threshold concentration (ITC) of 16 pollen allergens
using serial dilutions of allergen and intravenous fluorescein. The hypothesis
tested was that feline IDT currently is performed at suboptimal allergen
concentrations for pollens. ANIMALS: Twenty privately owned healthy clinically
nonallergic cats. METHODS: IDT was performed in duplicate using 16 pollen
allergens (weeds, grasses and trees) at a dilution of 8000 PNU/mL. Two blinded
investigators graded the test reactions independently using subjective and
objective criteria. Intravenous fluorescein was then administered and the test
reactions were re-evaluated. IDT was repeated for any allergen that was positive,
using serial dilutions of allergen at a concentration of 6000 and 4000 PNU/mL.
RESULTS: The ITC for 2 of 16 of the allergens was determined. The ITC of Cynodon
dactylon (Bermuda grass) and Schinus spp. (Peppercorn) was determined to be
between 6000 and 8000 PNU/mL. The ITC of all other allergens tested in this study
was >8000 PNU/mL. CONCLUSIONS AND CLINICAL IMPORTANCE: This study confirms that
suboptimal allergen concentrations currently are used for feline IDT as the ITC
is >8000 PNU/mL for 14 of 16 of the grass, weed and tree pollens evaluated. The
ITC of Cynodon dactylon and Schinus spp. was determined to be between 6000 and
8000 PNU/mL.
PMID- 28503779
TI - Normal amniotic fluid volume across gestation: Comparison of statistical
approaches in 1190 normal amniotic fluid volumes.
AB - AIM: Ultrasound estimation and evaluation of amniotic fluid volume (AFV) is an
important component of pregnancy surveillance and fetal well-being. The purpose
of this study was to compare and contrast four statistical methods used to
construct gestational age-specific reference intervals for the assessment of AFV.
METHODS: A total of 1095 normal AFV derived from four studies that measured AFV
using dye-dilution or direct measurement at the time of hysterotomy were used to
construct reference intervals using polynomial regression, quantile regression,
Royston and Wright mean and SD, and Cole's lambda mu sigma (LMS) methods. The
2.5th, 5th, 50th, 95th, and 97.5th centiles were derived for each statistical
method. RESULTS: AFV increased curvilinearly from 15 gestational weeks and
onward. Based on the 50th centile, the maximum value occurred at 30 weeks'
gestation for the polynomial regression and mean and SD methods while the maximum
was achieved at week 31 for the quantile regression and LMS methods. When data
were sparse, the quantile regression method produced dramatically different
estimates at the higher centile. CONCLUSION: The four statistical methods
produced similar results at gestational ages in which AFV was high. The quantile
regression approach, however, produces results that are more reflective of the
data when the data are sparse. Given the flexibility and robustness of the
quantile regression method, we recommend its use in constructing reference
intervals when the interest lies in the tails of the reference distribution.
PMID- 28503780
TI - A Case of a Chorionic Bump: New Sonographic-Histopathologic Findings With Review
of the Literature.
PMID- 28503778
TI - A Topical Zinc Ionophore Blocks Tumorigenic Progression in UV-exposed SKH-1 High
risk Mouse Skin.
AB - Nonmelanoma skin cancer (NMSC) is the most common malignancy in the United States
representing a considerable public health burden. Pharmacological suppression of
skin photocarcinogenesis has shown promise in preclinical and clinical studies,
but more efficacious photochemopreventive agents are needed. Here, we tested
feasibility of harnessing pharmacological disruption of intracellular zinc
homeostasis for photochemoprevention in vitro and in vivo. Employing the zinc
ionophore and FDA-approved microbicidal agent zinc pyrithione (ZnPT), used
worldwide in over-the-counter (OTC) topical consumer products, we first
demonstrated feasibility of achieving ZnPT-based intracellular Zn2+ overload in
cultured malignant keratinocytes (HaCaT-ras II-4; SCC-25) employing membrane
permeable fluorescent probes. Zinc overload was accompanied by induction of
intracellular oxidative stress, associated with mitochondrial superoxide release
as substantiated by MitoSOX RedTM fluorescence microscopy. ZnPT-induced cell
death observable in malignant keratinocytes was preceded by induction of metal
(MT2A), proteotoxic (HSPA6, HSPA1A, DDIT3, HMOX1) and genotoxic stress response
(GADD45A, XRCC2) gene expression at the mRNA and protein levels. Comet analysis
revealed introduction of formamidopyrimidine-DNA glycosylase (Fpg)-sensitive
oxidative DNA lesions. In a photocarcinogenesis model (UV-exposed SKH-1 high-risk
mouse skin), topical ZnPT administration post-UV caused epidermal zinc overload
and stress response gene expression with pronounced blockade of tumorigenesis.
Taken together, these data suggest feasibility of repurposing a topical OTC drug
for zinc-directed photochemoprevention of solar UV-induced NMSC.
PMID- 28503782
TI - Quantification of root water uptake in soil using X-ray computed tomography and
image-based modelling.
AB - Spatially averaged models of root-soil interactions are often used to calculate
plant water uptake. Using a combination of X-ray computed tomography (CT) and
image-based modelling, we tested the accuracy of this spatial averaging by
directly calculating plant water uptake for young wheat plants in two soil types.
The root system was imaged using X-ray CT at 2, 4, 6, 8 and 12 d after
transplanting. The roots were segmented using semi-automated root tracking for
speed and reproducibility. The segmented geometries were converted to a mesh
suitable for the numerical solution of Richards' equation. Richards' equation was
parameterized using existing pore scale studies of soil hydraulic properties in
the rhizosphere of wheat plants. Image-based modelling allows the spatial
distribution of water around the root to be visualized and the fluxes into the
root to be calculated. By comparing the results obtained through image-based
modelling to spatially averaged models, the impact of root architecture and
geometry in water uptake was quantified. We observed that the spatially averaged
models performed well in comparison to the image-based models with <2% difference
in uptake. However, the spatial averaging loses important information regarding
the spatial distribution of water near the root system.
PMID- 28503783
TI - Clinical and radiological features of an unusual fungal infection of shoulder.
PMID- 28503781
TI - Assessment of effect of CYP3A inhibition, CYP induction, OATP1B inhibition, and
high-fat meal on pharmacokinetics of the JAK1 inhibitor upadacitinib.
AB - AIMS: Upadacitinib (ABT-494) is a selective Janus kinase 1 inhibitor being
developed for treatment of auto-immune inflammatory disorders. This work
evaluated effects of high-fat meal, cytochrome P450 (CYP) 3A inhibition, CYP
induction, and organic anion transporting polypeptide (OATP) 1B inhibition on
upadacitinib pharmacokinetics. METHODS: Two Phase 1 evaluations were conducted,
each in 12 healthy subjects. In Study 1, using a randomized, two-sequence
crossover design, a 3 mg dose of upadacitinib (immediate-release capsules) was
administered alone under fasting conditions, after high-fat meal, or on Day 4 of
a 6-day regimen of 400 mg once-daily ketoconazole. In Study 2, a 12 mg
upadacitinib dose was administered alone, with the first, and with the eighth
dose of a 9-day regimen of rifampin 600 mg once daily. Upadacitinib plasma
concentrations were characterized. RESULTS: Administration of upadacitinib
immediate-release capsules after a high-fat meal decreased upadacitinib Cmax by
23% and had no impact on upadacitinib AUC relative to the fasting conditions.
Ketoconazole (strong CYP3A inhibitor) increased upadacitinib Cmax and AUC by 70%
and 75%, respectively. Multiple doses of rifampin (broad CYP inducer) decreased
upadacitinib Cmax and AUC by approximately 50% and 60%, respectively. A single
dose of rifampin (also an OATP1B inhibitor) had no effect on upadacitinib AUC.
Upadacitinib was well tolerated when co-administered with ketoconazole, rifampin,
or after a high-fat meal. CONCLUSIONS: Strong CYP3A inhibition and broad CYP
induction result in a weak and moderate effect, respectively, on upadacitinib
exposures. OATP1B inhibition and administration of upadacitinib immediate-release
formulation with food does not impact upadacitinib exposure.
PMID- 28503784
TI - Aryl hydrocarbon receptor and unexplained miscarriage.
AB - AIM: The aim of this study was to carry out a preliminary investigation of the
expression of aryl hydrocarbon receptor (AhR) in decidua and villus and the
relationship between AhR and unexplained miscarriage. METHODS: The expression of
AhR mRNA and protein from decidua and villus were measured using real-time
reverse transcription-polymerase chain reaction, western blot and
immunohistochemistry in 34 patients with unexplained miscarriage (miscarriage
group) and 38 women with normal early pregnancy (control group). RESULTS: The AhR
mRNA and protein expression was increased significantly in the villus in both
groups compared with decidua (P < 0.05, P < 0.05). In decidua, AhR mRNA and
protein expression in the miscarriage group was increased significantly compared
with the control group (P < 0.05, P < 0.05). In villus, AhR mRNA and protein
expression in the miscarriage group was increased significantly compared with the
control group (P < 0.05, P < 0.05). AhR is expressed mostly in the cytoplasm of
syncytiotrophoblasts in villus, and also in the cytoplasm of decidual cells.
CONCLUSIONS: AhR was expressed more in the villus than in the decidua, and the
upregulation of AhR mRNA and protein expression is associated with the
pathogenesis of unexplained miscarriage.
PMID- 28503785
TI - Novel Technique for Measurement of Fetal Right Myocardial Performance Index Using
Dual Gate Pulsed-Wave Doppler.
AB - OBJECTIVES: To evaluate the reproducibility of the fetal right myocardial
performance index determined by simultaneous recording of inflow and outflow
using a dual gate pulsed-wave Doppler (DD). METHODS: This was a prospective study
of 39 normal singleton fetuses. Two experienced operators each measured the right
myocardial performance index in three ways, twice: (1) separate recording of the
inflow and outflow using single-gate pulsed-wave Doppler (PD), (2) simultaneous
recordings of the inflow and outflow using tissue Doppler (TD), and (3)
simultaneous recordings of the inflow and outflow using DD. Intra- and
interoperator reproducibility were assessed with intraclass correlation
coefficients. The measurements from all three methods taken by the more
experienced operator were compared using Bland-Altman plots and mean differences.
RESULTS: For both operators, intra-operator reproducibility was the highest when
using DD, followed by PD, and TD. Interoperator agreement was the highest for PD
measurements, followed by DD, and TD. The smallest mean difference was between
the PD and DD measurements by the more experienced operator. There was a positive
correlation between PD and DD values (r = 0.369, P < .001). CONCLUSIONS: Dual
gate pulsed-wave Doppler may be an effective alternative to the PD or TD methods,
and can separately evaluate systolic and diastolic myocardial function.
PMID- 28503787
TI - Left lobe of liver in a Morgagni's hernia.
PMID- 28503786
TI - Use of fluorescent in-situ hybridisation in salivary gland cytology: A powerful
diagnostic tool.
AB - OBJECTIVE: Salivary gland cytology is challenging because it includes a diversity
of lesions and a wide spectra of tumours. Recently, it has been reported that
many types of salivary gland tumours have specific molecular diagnostic
signatures that could be identified by fluorescent in-situ hybridisation (FISH).
The aim of the present study was to demonstrate the feasibility and efficiency of
FISH on routine cytological salivary gland smears. METHODS: FISH was conducted on
37 cytological salivary gland smears from 34 patients. According to the
cytological diagnosis suspected, MECT1/MAML2 gene fusion and rearrangements of
PLAG1, MYB, or ETV6 were analysed. The presence and percentages of cells that had
gene rearrangements were evaluated. Results were compared with the histological
surgical samples, available from 26 patients. RESULTS: The PLAG1 rearrangement
was observed in 12/20 (60%) cases of pleomorphic adenoma. MECT1/MAML2 gene fusion
was observed in 1:2 mucoepidermoid carcinomas but was not observed in five other
tumours (two pleomorphic adenomas, one Warthin's tumour, one mammary analogue
secretory carcinoma [MASC] and one cystic tumour). MYB rearrangement was observed
in 4/4 adenoid cystic carcinomas. ETV6-gene splitting identified one MASC.
CONCLUSION: Overall, FISH had a specificity of 100% and a sensitivity of 66.7%.
When FISH and cytological analyses were combined, the overall sensitivity was
increased to 93.3%. It can thus be concluded that when the FISH analysis is
positive, the extent of surgery could be determined with confidence pre
operatively without needing a diagnosis from a frozen section.
PMID- 28503788
TI - Indicators of inappropriate tumour marker use through the mining of electronic
health records.
AB - RATIONALE, AIMS, AND OBJECTIVES: Although the issue of monitoring appropriateness
of tumour markers (TMs) request in outpatients remains crucial, proper indicators
are still demanding. The present study developed and explored indicators of
inappropriate TM ordering in outpatients through the data mining of electronic
health records (EHRs). METHODS: Carcinoembryonic antigen (CEA), alfa-fetoprotein
(AFP), carbohydrate antigen (CA)125, CA15.3, CA19.9, and prostate-specific
antigen (PSA) ordered in outpatients during a year were examined by mining EHRs
of a Local Health Authority in Italy. Evidence-based criteria were used to
develop performance indicators. Demographic and clinical information associated
with TM orders were examined. RESULTS: A total of 80 813 TMs were ordered in 52
536 outpatients (1.54 markers/patient). Indicators related to disease codes,
gender, age, and TM repetitions were developed, and their application showed that
(1) CA15.3 and CEA are prevalently requested in patients with cancer (79.2% and
65.6%) whereas the other TMs are largely requested also in patients without
cancer; (2) requests of PSA in women and of CA125 or CA15.3 in men are
negligible; (3) although requests in people older than 80 years are relevant
(16.4% of total), the highest rate of request of all markers occurs in patients
aged 40 to 79 years; (4) CA15.3 and CEA are mainly requested in cancer cases
between 50 and 79 years and AFP, CA19.9, and CA125 in those between 60 and 69
years; (5) <50% of PSA orders are associated with cancer code for all age
intervals; and (6) multiple repetitions of AFP, CA125, CA15.3, CA19.9, and CEA
are prevalent in cancer patients or benign diseases to which TMs are appropriate,
whereas PSA repetitions occur mainly in patients without cancer. CONCLUSIONS: The
developed indicators resulted suitable to monitor TM overordering in outpatients
through the mining of EHRs. The present study is a first approach towards the use
of big-data mining for TM appropriateness evaluation purposes.
PMID- 28503789
TI - Exploring the Structural Space of the Galectin-1-Ligand Interaction.
AB - Galectin-1 is a tumor-associated protein recognizing the Galbeta1-4GlcNAc motif
of cell-surface glycoconjugates. Herein, we report the stepwise expansion of a
multifunctional natural scaffold based on N-acetyllactosamine (LacNAc). We
obtained a LacNAc mimetic equipped with an alkynyl function on the 3'-hydroxy
group of the disaccharide facing towards a binding pocket adjacent to the
carbohydrate-recognition domain. It served as an anchor motif for further
expansion by the Sharpless-Huisgen-Meldal reaction, which resulted in ligands
with a binding mode almost identical to that of the natural carbohydrate
template. X-ray crystallography provided a structural understanding of the
galectin-1-ligand interactions. The results of this study enable the development
of bespoke ligands for members of the galectin target family.
PMID- 28503790
TI - Proton gradients at the origin of life.
AB - Chemiosmotic coupling - the harnessing of electrochemical ion gradients across
membranes to drive metabolism - is as universally conserved as the genetic code.
As argued previously in these pages, such deep conservation suggests that ion
gradients arose early in evolution, and might have played a role in the origin of
life. Alkaline hydrothermal vents harbour pH gradients of similar polarity and
magnitude to those employed by modern cells, one of many properties that make
them attractive models for life's origin. Their congruence with the physiology of
anaerobic autotrophs that use the acetyl CoA pathway to fix CO2 gives the
alkaline vent model broad appeal to biologists. Recently, however, a paper by Baz
Jackson criticized the hypothesis, concluding that natural pH gradients were
unlikely to have played any role in the origin of life. Unfortunately, Jackson
mainly criticized his own interpretations of the theory, not what the literature
says. This counterpoint is intended to set the record straight.
PMID- 28503793
TI - Rectus Abdominis Rhabdomyolysis: Report of 2 Cases.
AB - Exercise-induced rhabdomyolysis is an unusual clinical entity for physicians and
one that is frequently misdiagnosed. With the ever-increasing use of sonography
by radiologists, sonographers, and sports physicians in the diagnosis of acute
muscle injury, recognition of the typical sonographic appearance of
rhabdomyolysis is paramount. Current literature using high-resolution ultrasound
equipment is limited, with much of the literature offering dated or incongruent
descriptions. We describe the sonographic findings of hyperechoic muscle and a
hypoechoic halo of edema in 2 proven cases of rectus abdominis rhabdomyolysis
after exercise.
PMID- 28503791
TI - Blood Glucose and Insulin Concentrations after Octreotide Administration in
Horses With Insulin Dysregulation.
AB - BACKGROUND: Octreotide is a somatostatin analog that suppresses insulin
secretion. HYPOTHESIS: We hypothesized that octreotide would suppress insulin
concentrations in horses and that normal (N) horses and those with insulin
dysregulation (ID) would differ significantly in their plasma glucose and insulin
responses to administration of octreotide. ANIMALS: Twelve horses, N = 5, ID = 7.
METHODS: Prospective study. An oral sugar test was performed to assign horses to
N and ID groups. Octreotide (1.0 MUg/kg IV) was then administered, and blood was
collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, 75, and 90 minute, and 2, 3, 4, 6,
8, 12, and 24 hour for measurement of glucose and insulin concentrations. Area
under the curve (AUC) values were calculated. RESULTS: Mean AUC values for
glucose and insulin did not differ between normal (n = 5) and ID (n = 7) groups
after octreotide injection. Significant time (P < .001) effects were detected for
glucose and insulin concentrations. A group * time interaction (P = .091) was
detected for insulin concentrations after administration of octreotide, but the
group (P = .33) effect was not significant. CONCLUSIONS AND CLINICAL IMPORTANCE:
Octreotide suppresses insulin secretion, resulting in hyperglycemia, and then
concentrations increase above baseline as glycemic control is restored. Our
hypothesis that octreotide causes insulin concentrations to decrease in horses
was supported, but differences between N and ID groups did not reach statistical
significance when blood glucose and insulin responses were compared. The utility
of an octreotide response test remains to be determined.
PMID- 28503792
TI - Synthetic cannabinoid use in an acute psychiatric inpatient unit.
AB - In the present study, we explored the prevalence of new psychoactive substance
use by people admitted into an Australian acute public mental health facility
specializing in comorbid mental health and substance use. These substances have
since been banned from retail outlets, but the pattern of uptake and reasons
people use them is informative in terms of motivations and the management of
substance use more generally. A cross-sectional study to explore the use of
synthetic cannabis by people admitted to an acute adult mental health unit was
undertaken. Associations with diagnostic, service use, and demographic profiles
were explored. Fifty-six percent of people reported having used at least one type
of new psychoactive substance, including 53.5% who reported using synthetic
cannabis alone, and 18.8% who reported using both synthetic cannabis and other
new psychoactive substances. Synthetic cannabis use was not associated with any
demographic or diagnostic groups. Legality and availability (43% combined) were
common reasons for use, along with the feeling of intoxication (20%). The high
prevalence of new psychoactive substance use adds weight to the recommendation
that clinicians should routinely screen for substances from the time of
admission. Accurate information about these substances is required in order to
provide accurate guidance and appropriate interventions to people in their care.
PMID- 28503794
TI - Estimated glomerular filtration rate on postoperative day 1 is associated with
renal functional outcome after percutaneous renal cryoablation for renal tumors.
PMID- 28503796
TI - Influence of an intentionally induced posterior lens capsule rupture on the real
time intraocular pressure during phacoemulsification in canine ex vivo eyes.
AB - OBJECTIVE: To evaluate the changes in the intraocular pressure (IOP) following an
intentionally induced posterior lens capsule rupture (PLCR) during
phacoemulsification in enucleated canine eyes. Furthermore, to compare the IOPs
between different stages of phacoemulsification for two different bottle heights
(BH). PROCEDURES: Coaxial phacoemulsification was performed using a venturi-based
machine at a 60 or 90 cm BH. A pressure transducer, inserted into the anterior
chamber through the peripheral cornea, monitored real-time IOP. For one half of
the lens, the sculpt-segment removal (SS) was followed by irrigation/aspiration
(IA). The PLCR was intentionally created, and the SS and IA were repeated on the
residual lens fragments. RESULTS: For the 60 cm BH, the mean IOP following the
PLCR was significantly higher than before the PLCR during SS (28.30 +/- 12.56 and
38.71 +/- 9.43 mmHg before and after PLCR, respectively) and IA (42.76 +/- 12.46
and 47.88 +/- 7.10 mmHg before and after PLCR, respectively) stages (P < 0.001).
For the 90 cm BH, the mean IOP following the PLCR was also significantly higher
than before the PLCR during SS (33.39 +/- 11.09 and 58.17 +/- 6.89 mmHg before
and after PLCR, respectively) and IA (62.39 +/- 12.46 and 72.04 +/- 8.59 mmHg
before and after PLCR, respectively) stages (P < 0.001). CONCLUSIONS: The
occurrence of a PLCR led to an increase in IOP during both the SS and IA stages.
The elevated IOP after the PLCR might be one of the most important factors for
ocular tissue damage, as it reduces ocular perfusion. Additionally, the BH should
be reduced following PLCR to prevent complications stemming from the raised IOP.
PMID- 28503795
TI - Automatic detection of paroxysmal atrial fibrillation in patients with ischaemic
stroke: better than routine diagnostic workup?
AB - BACKGROUND AND PURPOSE: Prolonged electrocardiogram (ECG) monitoring after
ischaemic stroke increases the diagnostic yield of paroxysmal atrial fibrillation
(pAF). In order to facilitate the additional workload involved in ECG analysis
due to prolonged monitoring times, we investigated the effectiveness of pAF
detection with an automated software algorithm (SA) in comparison to the routine
staff-based analysis (RA) during standard stroke-unit care. Therefore, patients
with acute ischaemic stroke or transitory ischaemic attack presenting with sinus
rhythmus on the admission ECG and no history of atrial fibrillation were
prospectively included. METHODS: A 24-h Holter ECG assessment was performed using
either RA based on a computer-aided evaluation and subsequent review by a
cardiologist or a commercially available automated SA. In the case of discordant
results concerning the occurrence of pAF between the two methods, the data
underwent an independent external rating. RESULTS: Of 809 prospectively enrolled
patients, 580 patients fulfilled the inclusion criteria. pAF was ultimately
diagnosed in 3.3% of the cohort (19 patients). SA and RA correctly diagnosed pAF
in 17 patients resulting in a comparable diagnostic effectiveness of the analysis
methods (sensitivity: SA 89.5% vs. RA 89.5%; specificity: SA 99.3% vs. RA 99.1%;
kappa, 0.686; P < 0.001; 95% confidence interval, 0.525-0.847). RA revealed
clinically relevant ECG abnormalities in an additional seven patients.
CONCLUSIONS: Although it should not completely replace RA, SA-based evaluation of
Holter ECG reaches a high diagnostic effectiveness for the detection of pAF and
can be used for a rapid and resource-saving analysis of ECG data to deal with
prolonged monitoring times.
PMID- 28503797
TI - The Nanomechanics of Lipid Multibilayer Stacks Exhibits Complex Dynamics.
AB - The nanomechanics of lipid membranes regulates a large number of cellular
functions. However, the molecular mechanisms underlying the plastic rupture of
individual bilayers remain elusive. This study uses force clamp spectroscopy to
capture the force-dependent dynamics of membrane failure on a model
diphytanoylphosphatidylcholine multilayer stack, which is devoid of surface
effects. The obtained kinetic measurements demonstrate that the rupture of an
individual lipid bilayer, occurring in the bilayer parallel plane, is a
stochastic process that follows a log-normal distribution, compatible with a pore
formation mechanism. Furthermore, the vertical individual force-clamp
trajectories, occurring in the bilayer orthogonal bilayer plane, reveal that
rupturing process occurs through distinct intermediate mechanical transition
states that can be ascribed to the fine chemical composition of the hydrated
phospholipid moiety. Altogether, these results provide a first description of
unanticipated complexity in the energy landscape governing the mechanically
induced bilayer rupture process.
PMID- 28503798
TI - Neutral and alkaline cellulases: Production, engineering, and applications.
AB - Neutral and alkaline cellulases from microorganisms constitute a major group of
the industrial enzymes and find applications in various industries. Screening is
the important ways to get novel cellulases. Most fungal cellulases have acidic pH
optima, except some fungi like Humicola insolens species. However, new
applications require the use of neutral and alkaline cellulases in food, brewery
and wine, animal feed, textile and laundry, pulp and paper industries,
agriculture as well in scientific research purposes. Indeed, the demand for these
enzymes is growing more rapidly than ever before, and becomes the driving force
for research on engineering the cellulolytic enzymes. Here, we present an
overview of the biotechnological research for neutral and alkaline cellulases.
PMID- 28503799
TI - Lymph node dissection for Siewert II esophagogastric junction adenocarcinoma: a
retrospective study of 136 cases.
AB - BACKGROUND: To compare the lymph node dissection with the right transthoracic
Ivor-Lewis (IL) procedure to that with the left transthoracic (LT) approach for
Siewert type II adenocarcinoma of the esophagogastric (AEG) junction. METHODS: In
this study, 136 patients with Siewert type II AEG who met the inclusion criteria
underwent surgical resection were divided into the IL (47 cases) and LT (89
cases) groups. The number and frequency of the dissected lymph nodes in each
station were compared between the two groups. RESULTS: The IL group had a longer
proximal surgical margin (P = 0.000) and more total (P = 0.000), thoracic (P =
0.000), and abdominal lymph nodes (P = 0.000) dissected than the LT group. In
general, the IL group had a higher dissection rate in each thoracic lymph node
station (P < 0.05) than the LT group. The dissection rates of the hepatic artery,
splenic artery and celiac trunk lymph nodes were higher in the IL group than in
the LT group (P < 0.05). The lymph node metastasis rate was 78.7% in the IL
group, higher than the 61.8% in the LT group (P = 0.045). CONCLUSIONS: The right
transthoracic IL procedure was demonstrated to be a better application than the
LT approach for Siewert type II AEG in terms of the number and frequency of lymph
node resections.
PMID- 28503800
TI - Secular trends in Australian school children's sleep and perceived importance of
sleep between 1985 and 2013.
AB - AIM: To examine secular trends in Australian children's actual sleep time as well
as the perceived importance of sleep between 1985, 2004 and 2013. METHODS:
Secular trends in children's sleep and their perception of the importance of
sleep across three time points 1985 (N = 401), 2004 (N = 450) and 2013 (N = 395)
were examined according to socio-economic status (SES), age and sex. The children
self-reported their bedtime, wake-up time and their perceived importance of
sleep, among other questions. RESULTS: There were no significant differences in
sleep duration between boys and girls in any of the survey years, nor were there
differences in sleep duration between SES categories at any time point.
Independent of survey year, age, sex and SES, there was a graded difference in
sleep duration (minutes) across response categories for perceived importance of
sleep. Overall, trends in the perceived importance of sleep appeared to match
trends in actual sleep time, but not for all subgroups. CONCLUSION: This study
indicates that the sleep duration of high SES Australian school children is
returning to, or near to, baseline sleep duration observed in 1985, while the
sleep duration of low SES Australian children has remained at low levels.
PMID- 28503802
TI - Electrospun polyethersolfone nanofibrous membrane as novel platform for protein
immobilization in microfluidic systems.
AB - In the present study, the feasibility of electrospun polyethersolfone (PES)
nanofibrous membrane as the solid substrate for microfluidic based immunoassays
to enhance the density of immobilized antibody on the surface of membrane was
assessed. Conversely, the efficacy of antibody immobilization was compared by two
different strategies as 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC)/N
Hydroxysuccinimide (NHS) coupling chemistry and hydrophobic interaction. Compared
to conventional immunoassays carried out in plates or gels, microfluidic based
immunoassays grant a lot of advantages such as a consumption of little samples
and reagents, shorter analysis time, and higher efficiency. Therefore,
microfluidic immunoassays can be efficiently used as a point-of-care device in
medical diagnosis. Surprisingly, we found the increase of specific surface areas
of the microfluidic channels improve density of immobilized proteins and leads to
higher signal strength. Anti-staphylococcus enterotoxin B (anti-SEB) was used as
an analyte model to demonstrate the utility of our proposed platform. Fluorescent
microscopy, Fourier transform infrared spectroscopic (FTIR), gas adsorption,
contact angle, X-ray photoelectron spectroscopy (XPS), scanning electron
microscopy (SEM), Uv-Vis spectrophotometer and atomic force microscopy (AFM)
techniques were used to assess the efficacy of antibody immobilization on the
surface. To understand dominant mechanism of protein immobilization, zeta
potential measurement was also carried out and it was found electrostatic
attraction play significant role in antibody immobilization running into micro-
channels containing through EDC/NHS. Moreover, incorporation of nanofibrous
membrane causes significant improvement in the signal detection of microfluidic
based immunoassay. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B:
Appl Biomater, 106B: 1108-1120, 2018.
PMID- 28503801
TI - Pioppino mushroom in southern Italy: an undervalued source of nutrients and
bioactive compounds.
AB - BACKGROUND: Agrocybe aegerita (V. Brig.) Singer, commonly known as Pioppino, is a
popular edible mushroom, known in the Campania Region (Italy). Despite its
habitual consumption, little nutritional and biochemical information is
available. Thus, nutritional values, anti-radical properties and chemical
composition of the wild Pioppino were compared to those of the cultivated
Agaricus bisporus (J.E. Lange) Imbach (known as Champignon), equally analysed.
RESULTS: Macronutrient components (proteins, carbohydrates and lipids), free and
protein amino acids and fatty acid content of poplar mushroom were achieved.
Total phenol content of a defatted Pioppino alcoholic extract (PM) was
determined, whereas DPPH and ABTS methods were applied to determine the radical
scavenging capabilities of the extract. Ferricyanide and ORAC-fluorescein methods
were also performed. Finally, LC-HRMS was used to identify and quantify the main
metabolites in the extract. PM was mainly constituted of disaccharides, hexitol
derivatives and malic acid. Coumaric acid isomers and C6 C1 compounds were also
detected. CONCLUSION: All data revealed that wild Pioppino is an excellent
functional food, by far exceeding that of the Champignon. Therefore, these data
are useful to promote the consumption of this mushroom encouraging thus its
biological cultivation, due to wild availability is strongly compromised by the
extensive use of fungicides. (c) 2017 Society of Chemical Industry.
PMID- 28503803
TI - A microstructural study of the pleon-holding mechanism in Carcinus maenas
(Decapoda, Brachyura, Portunoidea, Carcinidae) of different sizes.
AB - Within the Brachyura there are a variety of specialized holding mechanisms, which
facilitate the close attachment of the highly reduced pleon underneath the
cephalothorax. The most common mechanism in eubrachyurans, known as the press
button, consists of a sternal protrusion and a corresponding pleonal socket.
Reports on the microstructural properties of the surface of these holding
structures are scarce and patchy. In this study, the European Green Crab Carcinus
maenas, is used as model to describe the microstructure of a typical press-button
mechanism with the use of scanning electron microscopy and light microscopic
histology. A highly tuberculate cuticle and an apical ridge on the sternal knob
are found in juveniles of both sexes. The microstructures are lost in adult
males. In adult females, the holding structures themselves are reduced, but never
completely lost. These findings show that C. maenas does not undergo a single
"final puberty moult," after which all juvenile characteristics are lost, as
previously assumed. Further comparison of the morphology of juveniles to another
species indicates a close resemblance of the holding structures at this stage.
Therefore, the use of the microstructure of the pleon-holding mechanism for
phylogenetic analysis is restricted to adult specimens.
PMID- 28503804
TI - Neural correlates of visuomotor adjustments during scaling of human finger
movements.
AB - Visually guided finger movements include online feedback of current effector
position to guide target approach. This visual feedback may be scaled or
otherwise distorted by unpredictable perturbations. Although adjustments to
visual feedback scaling have been studied before, the underlying brain activation
differences between upscaling (visual feedback larger than real movement) and
downscaling (feedback smaller than real movement) are currently unknown. Brain
activation differences between upscaling and downscaling might be expected
because within-trial adjustments during upscaling require corrective backwards
accelerations, whereas correcting for downscaling requires forward accelerations.
In this behavioural and fMRI study we investigated adjustments during up- and
downscaling in a target-directed finger flexion-extension task with real-time
visual feedback. We found that subjects made longer and more complete within
trial corrections for downscaling perturbations than for upscaling perturbations.
The finger task activated primary motor (M1) and somatosensory (S1) areas,
premotor and parietal regions, basal ganglia, and cerebellum. General scaling
effects were seen in the right pre-supplementary motor area, dorsal anterior
cingulate cortex, inferior parietal lobule, and dorsolateral prefrontal cortex.
Stronger activations for down- than for upscaling were observed in M1,
supplementary motor area (SMA), S1 and anterior cingulate cortex. We argue that
these activation differences may reflect differing online correction for
upscaling vs. downscaling during finger flexion-extension.
PMID- 28503805
TI - Development of a SiYAlON glaze for improved osteoconductivity of implantable
medical devices.
AB - The application of bioactive coatings onto orthopaedic appliances is commonly
performed to compensate for the otherwise bioinert nature of medical devices and
to improve their osseointegration. Calcium phosphates, hydroxyapatite (HAp), and
bioglasses are commercially available for this purpose. Until recently, few other
inorganic compounds have been identified with similar biofunctionality. However,
silicon nitride (Si3 N4 ) has emerged as a new orthopaedic material whose unique
surface chemistry also enhances osteoconductivity. Recent research has confirmed
that its minority intergranular phase, consisting of silicon yttrium aluminum
oxynitride (SiYAlON), is principally responsible for this improvement. As a
result, it was hypothesized that SiYAlON itself might serve as an effective
osteoconductive coating or glaze for medical devices. To test this hypothesis, a
process inspired by traditional ceramic whiteware glazing was developed. A slurry
containing ingredients similar to the intergranular SiYAlON composition was
applied to a Si3 N4 surface, which was then subjected to a heat treatment to form
a glaze. Various analytical tools were employed to assess its chemistry and
morphology. It was found that the glaze was comprised predominately of Y5 Si3 O12
N, a compound commonly referred to as N-apatite, which is isostructural to native
HAp. Subsequent exposure of the glazed surface to acellular simulated body fluid
led to increased deposition of biomimetic HAp-like crystals, while exposure to
Saos-2 osteosarcoma cells in vitro resulted in greater HAp deposition relative to
control samples. The observation that SiYAlON exhibits enhanced osteoconductivity
portends its potential as a therapeutic aid in bone and tissue repair. (c) 2017
Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1084
1096, 2018.
PMID- 28503806
TI - Distinctiveness Benefits Novelty (and Not Familiarity), but Only Up to a Limit:
The Prior Knowledge Perspective.
AB - Novelty is a pivotal player in cognition, and its contribution to superior memory
performance is a widely accepted convention. On the other hand, mnemonic
advantages for familiar information are also well documented. Here, we examine
the role of experimental distinctiveness as a potential explanation for these
apparently conflicting findings. Across two experiments, we demonstrate that
conceptual novelty, an unfamiliar combination of familiar constituents, is
sensitive to its experimental proportions: Improved memory for novelty was
observed when novel stimuli were relatively rare. Memory levels for familiar
items, in contrast, were completely unaffected by experimental proportions,
highlighting their insensitivity to list-based distinctiveness. Finally, no
mnemonic advantage for conceptual novelty over familiarity was observed even when
novel stimuli were extremely rare at study. Together, these results imply that
novel and familiar items are processed via partially distinct mechanisms, with
(at least some facets of) novelty not providing a mnemonic advantage over
familiarity.
PMID- 28503807
TI - Reducing anti-nutritional factor and enhancing yield with advancing time of
planting and zinc application in grasspea in Ethiopia.
AB - BACKGROUND: Grasspea (Lathyrus sativus L.) is an important pulse crop for food,
feed and sustainable crop production systems in Ethiopia. Despite its advantages
in nutrition and adaptability to harsh climate and low fertile soil, it contains
a neurotoxin, beta-N-oxalyl-alpha,beta-diamiono propionic acid (beta-ODAP), which
paralyses the lower limbs and is affected by genotypic and agronomic factors. To
determine the effect of zinc application and planting date on yield and beta-ODAP
content of two genotypes, experiments were conducted in two regions of Ethiopia.
RESULTS: The main effects of variety, sowing date and zinc and their interactions
were significant (P < 0.001) for beta-ODAP and seed yield, which had a linear
relationship with zinc. For the improved grasspea variety, an application of 20
kg ha-1 zinc showed a reduction of beta-ODAP from 0.15% to 0.088% at Debre Zeit
and 0.14% to 0.08% at Sheno and increased its yield from 841 kg ha-1 to 2260 kg
ha-1 at Debre Zeit and from 715 to 1835 kg ha-1 at Sheno. Early sowing showed a
reduction in ODAP content in relation to the late sowing. CONCLUSION: An
application of Zn beyond even 20 kg ha-1 with an early sowing is recommended for
the improved variety. (c) 2017 Society of Chemical Industry.
PMID- 28503808
TI - A pilot randomized study comparing extralevator with conventional
abdominoperineal excision for low rectal cancer after neoadjuvant chemoradiation.
AB - AIM: The aims of this study were to assess the feasibility of performing an
extralevator abdominoperineal excision (ELAPE) after neoadjuvant chemoradiation
(NCRT), to compare the rates of circumferential resection margin (CRM)
involvement and intra-operative perforation (IOP) of the specimen, and to assess
the amount of tissue removed around the muscularis propria (MP)/internal
sphincter (IS) of the lower rectum in patients with low rectal cancer undergoing
ELAPE compared with conventional abdominoperineal excision (CAPE) after NCRT.
METHOD: This was an open-label, parallel-arm pilot randomized trial conducted in
India. Twenty patients were randomized to one of the study arms. The surgical
specimens were fixed, serially cross-sectioned and photographed. Using
specialized morphometry software, the amount of tissue resected with each
operation was measured. RESULTS: There was a nonsignificant trend towards more
IOPs (30% vs 0%, P = 0.06) and a higher CRM involvement rate (40% vs 20%, P =
0.32) in the CAPE arm. ELAPE removed a significantly greater amount of tissue
around the IS/MP when compared with CAPE (mean +/- SD: 1911.39 +/- 382 mm2 vs
1132.03 +/- 371 mm2 , P < 0.001). The mean distance from the IS/MP to the CRM was
significantly greater in the ELAPE arm both in the posterior (mean +/- SD: 28.28
+/- 3 mm vs 9.63 +/- 3 mm, P < 0.001) and lateral (mean +/- SD: 13.69 +/- 3 mm vs
9.72 +/- 3 mm, P = 0.009) parts of the rectum but not in the anterior part (mean
+/- SD: 6.74 +/- 2 mm vs 6.10 +/- 4 mm, P = 0.64). The short-term morbidity was
not significantly different between the two procedures. CONCLUSION: ELAPE removed
more tissue in the lower rectum and resulted in a lower rate of IOP and CRM
involvement when compared with CAPE, even after NCRT.
PMID- 28503809
TI - Robot-assisted laparoscopic versus open partial nephrectomy in patients with
chronic kidney disease: A propensity score-matched comparative analysis of
surgical outcomes.
AB - OBJECTIVES: To compare surgical outcomes between robot-assisted laparoscopic
partial nephrectomy and open partial nephrectomy in patients with chronic kidney
disease. METHODS: Of 550 patients who underwent partial nephrectomy between 2012
and 2015, 163 patients with T1-2 renal tumors who had an estimated glomerular
filtration rate between 30 and 60 mL/min/1.73 m2 , and underwent robot-assisted
laparoscopic partial nephrectomy or open partial nephrectomy were retrospectively
analyzed. To minimize selection bias between the two surgical methods, patient
variables were adjusted by 1:1 propensity score matching. RESULTS: The present
study included 75 patients undergoing robot-assisted laparoscopic partial
nephrectomy and 88 undergoing open partial nephrectomy. After propensity score
matching, 40 patients were included in each operative group. The mean
preoperative estimated glomerular filtration rate was 49 mL/min/1.73 m2 . The
mean ischemia time was 21 min in robot-assisted laparoscopic partial nephrectomy
(warm ischemia) and 35 min in open partial nephrectomy (cold ischemia).
Preservation of the estimated glomerular filtration rate 3-6 months
postoperatively was not significantly different between robot-assisted
laparoscopic partial nephrectomy and open partial nephrectomy (92% vs 91%, P =
0.9348). Estimated blood loss was significantly lower in the robot-assisted
laparoscopic partial nephrectomy group than in the open partial nephrectomy group
(104 vs 185 mL, P = 0.0025). The postoperative length of hospital stay was
shorter in the robot-assisted laparoscopic partial nephrectomy group than in the
open partial nephrectomy group (P < 0.0001). The prevalence of Clavien-Dindo
grade 3 complications and a negative surgical margin status were not
significantly different between the two groups. CONCLUSIONS: In our experience,
robot-assisted laparoscopic partial nephrectomy and open partial nephrectomy
provide similar outcomes in terms of functional preservation and perioperative
complications among patients with chronic kidney disease. However, a lower
estimated blood loss and shorter postoperative length of hospital stay can be
obtained with robot-assisted laparoscopic partial nephrectomy.
PMID- 28503811
TI - The Interactive Origin of Iconicity.
AB - We investigate the emergence of iconicity, specifically a bouba-kiki effect in
miniature artificial languages under different functional constraints: when the
languages are reproduced and when they are used communicatively. We ran
transmission chains of (a) participant dyads who played an interactive
communicative game and (b) individual participants who played a matched learning
game. An analysis of the languages over six generations in an iterated learning
experiment revealed that in the Communication condition, but not in the
Reproduction condition, words for spiky shapes tend to be rated by naive judges
as more spiky than the words for round shapes. This suggests that iconicity may
not only be the outcome of innovations introduced by individuals, but, crucially,
the result of interlocutor negotiation of new communicative conventions. We
interpret our results as an illustration of cultural evolution by random mutation
and selection (as opposed to by guided variation).
PMID- 28503810
TI - A minor role of asparaginase in predisposing to cerebral venous thromboses in
adult acute lymphoblastic leukemia patients.
AB - Cerebral venous thrombosis (CVT) covers up to a third of all venous thromboses
(VTs) detected in patients with acute lymphoblastic leukemia (ALL). It usually
hampers patients' lives and may also endanger efficient leukemia treatment.
Although many factors have been suggested to account for an elevated risk of VTs
in patients with ALL, there still is a lack of studies focusing on CVTs and
especially in the setting of adult ALL patients. We studied in our retrospective
population-based cohort the occurrence, characteristics, as well as risk factors
for VTs in 186 consecutively diagnosed Finnish adult ALL patients treated with a
national pediatric-inspired treatment protocol ALL2000. In the risk factor
analyses for VTs we found a distinction of the characteristics of the patients
acquiring CVT from those with other kinds of VTs or without thrombosis. In
contrast to previous studies we were also able to compare the effects of
asparaginase in relation to CVT occurrence. Notably, more than half of the CVTs
were diagnosed prior the administration of asparaginase which accentuates the
role of other risk factors on the pathophysiology of CVT compared to truncal or
central venous line (CVL) VTs in adult ALL patients.
PMID- 28503812
TI - The difference between cycloplegic and non-cycloplegic autorefraction and its
association with progression of refractive error in Beijing urban children.
AB - PURPOSE: To investigate the difference between cycloplegic and non-cycloplegic
autorefraction and its association with the progression of refractive error in
Beijing urban children. METHODS: A total of 386 children aged 6-17 years were
enrolled in the baseline investigation of the Beijing Myopia Progression Study in
2010. They were invited for follow-up vision examinations in the years 2011,
2012, and 2013, including cycloplegic (cyclopentolate 1%, three times)
autorefraction. We investigated the difference between the cycloplegic spherical
equivalent (SE) and the non-cycloplegic SE (DSE) provided by autorefraction and
its association with refractive error progression. The progression of refractive
error was defined as the difference between the cycloplegic SE at follow-up and
at baseline. RESULTS: Two hundred and nineteen children (57%) with completed
refractive data (mean +/- standard deviation: -1.36 +/- 2.44 D at baseline) were
ultimately enrolled. The DSE reduced from 0.51 +/- 0.72 D at baseline to 0.19 +/-
0.43 D in the third year of follow-up (p = 0.01). The baseline DSE was positively
associated with the children's baseline cycloplegic refraction (beta = 0.193
dioptre dioptre-1 , p < 0.001). After further divided by refractive status, the
DSE was consistently higher in the hyperopic group than in either the emmetropic
or myopic groups at each follow-up (all p < 0.001). In the multivariate
regression analysis, the myopic children with larger baseline DSE (beta = -0.404
dioptre dioptre-1 , p = 0.01) exhibited more myopic refractive change. However,
baseline DSE was not found to be a significant risk factor (relative risk, 95%
confidence interval: 1.06, 0.79-1.41) for those with newly developed myopia.
CONCLUSION: In this sample, the children's DSE was found to be increased as the
hyperopic refraction increased. Furthermore, greater the DSE was associated with
the progression of refractive error among the myopic children, but not with the
onset of myopia.
PMID- 28503813
TI - Molecular characterization of equine infectious anaemia virus from a major
outbreak in southeastern France.
AB - In 2009, a major outbreak of equine infectious anaemia (EIA) was reported in the
south-east of France. This outbreak affected three premises located in the Var
region where the index case, a 10-year-old mare that exhibited clinical signs
consistent with EIA, occurred at a riding school. Overall, more than 250 horses
were tested for EIAV (equine infectious anaemia virus) antibodies, using agar gel
immunodiffusion test, and 16 horses were positive in three different holdings.
Epidemiological survey confirmed that the three premises were related through the
purchase/sale of horses and the use of shared or nearby pastures. Molecular
characterization of viruses was performed by sequencing the full gag gene
sequence (1,400 bp) of the proviral DNAs retrieved from the spleen of infected
animals collected post-mortem. Phylogenetic analysis confirmed epidemiological
data from the field, as viruses isolated from the three premises were clustering
together suggesting a common origin whereas some premises were 50 km apart.
Moreover, viruses characterized during this outbreak are different from European
strains described so far, underlying the high genetic diversity of EIAV in
Europe.
PMID- 28503814
TI - Diabetes mellitus and risk of early-onset Alzheimer's disease: a population-based
case-control study.
AB - BACKGROUND AND PURPOSE: Previous studies have reported that diabetes is a risk
factor for both all-cause and vascular dementia; however, diabetes as a risk
factor for Alzheimer's disease (AD) remains controversial. Therefore, the aim was
to elucidate the association between diabetes and early-onset AD. METHODS: A case
control study was conducted using a population-based database that included
medical and pharmacy claims and insurance eligibility data, from beneficiaries of
corporate employees and their dependent family members. Cases were aged 40-64
years and were first prescribed medications for AD between 2005 and 2016. Up to
four controls matched for age, sex and hospital type were included for each case.
Data were analyzed using conditional logistic regression and compared between the
sexes. RESULTS: Data from 371 patients with AD (mean age 56.3 +/- 5.3 years; 48%
female) and 1484 controls were analyzed. Use of antidepressants, antipsychotics
and antithrombotics during the index month was higher amongst patients with AD
(19.4%, 34.5% and 11.3%, respectively) than amongst controls (2.9%, 10.3% and
7.3%, respectively). Our findings suggest no evidence for an association between
diabetes and risk of early-onset AD (adjusted odds ratio 1.31; 95% confidence
interval 0.90-1.92). In the subgroup analyses, adjusted odds ratios in patients
with diabetes were 0.73 (95% confidence interval 0.38-1.39) and 1.68 (95%
confidence interval 1.06-2.67) for female and male patients, respectively.
CONCLUSIONS: There is no apparent association between diabetes and risk of early
onset AD in the total study population, although a weak association was observed
amongst male patients.
PMID- 28503815
TI - Body Mass Normalization for Lateral Abdominal Muscle Thickness Measurements in
Adolescent Athletes.
AB - OBJECTIVES: To determine the value of allometric parameters for ultrasound
measurements of the oblique external (OE), oblique internal (OI), and transversus
abdominis (TrA) muscles in adolescent athletes. The allometric parameter is the
slope of the linear regression line between the log-transformed body mass and log
transformed muscle size measurement. METHODS: The study included 114 male
adolescent football players between the ages of 10 and 19 years. All individuals
with no surgical procedures performed on the trunk area and who had played a
sport for at least 2 years were included. A real-time B-mode ultrasound scanner
with a linear array transducer was used to obtain images of the lateral abdominal
muscles from both sides of the body. A stabilometric platform was used to assess
the body mass value. RESULTS: The correlations between body mass and the OE, OI,
and TrA muscle thicknesses were r = 0.73, r = 0.79, and r = 0.64, respectively
(in all cases, P < .0001). The allometric parameters were 0.77 for the OE, 0.67
for the OI, and 0.61 for the TrA. Using these parameters, no significant
correlations were found between body mass and the allometric-scaled thickness of
the lateral abdominal muscles. CONCLUSIONS: Significant positive correlations
exist between body mass and lateral abdominal muscle thickness in adolescent
athletes. Therefore, it is reasonable to advise that the values of the allometric
parameters for the OE, OI, and TrA muscles obtained in this study should be used,
and the allometric-scaled thicknesses of those muscles should be analyzed in
future research on adolescent athletes.
PMID- 28503817
TI - Influence of feeding a fish oil-containing diet to mature, overweight dogs:
Effects on lipid metabolites, postprandial glycaemia and body weight.
AB - The objective of this study was to determine the effect of feeding a fish oil
(FO)-containing diet on lipid and protein metabolism, postprandial glycaemia and
body weight (BW) of mature, overweight dogs. Seven female dogs were randomly
assigned to one of two isonitrogenous and isocaloric diets, control (CO) or FO
(FO), in a crossover design. Experimental periods were 69 day, separated by a
washout period of 30 day. At the beginning of the experiment, and at 30 and 60
day of feeding the experimental diets, the dogs were infused with D-glucose (2
g/kg BW) through an intravenous catheter. Blood samples were collected for 3 hr
to perform a glucose tolerance test. Nitrogen balance measurements began at 06:30
on d 63 of each experimental period and ended at 06:30 on d 69. On d 66 of each
period, a single dose (7.5 mg/kg) of 15 N-glycine was administered orally for
determination of protein turnover. Incremental area under the curve and glucose
concentration at peak did not differ between treatments or among sampling days
within treatment. Glucose half-life tended to decrease (p < .10) in the FO
treatment on day 30 when compared to baseline (day 0). beta-hydroxybutyrate, non
esterified fatty acid (NEFA) and triglycerides did not differ within or between
treatments. Cholesterol decreased (p < .05) on the FO treatment on day 30, 60 and
69 when compared to day 0. High-density lipoprotein (HDL) decreased (p < .05) in
the FO treatment on day 69 when compared to day 0. Body weight, food intake,
faecal excretion, DM and N digestibilities, N balance and protein turnover were
not different between diets. Overall, FO-containing diet decreases cholesterol in
mature overweight dogs; however, further research is warranted to verify the
effects of FO on glucose metabolism.
PMID- 28503816
TI - Xanthophylls increased HDLC level and nuclear factor PPARgamma, RXRgamma and
RARalpha expression in hens and chicks.
AB - This study was designed to investigate effects of xanthophylls on serum lipid
profile (triglyceride, TG; cholesterol, CHO; high-density lipoprotein
cholesterol, HDLC; and low-density lipoprotein cholesterol, LDLC) and nuclear
factor (peroxisome proliferator-activated receptor gamma, PPARgamma; PPAR gamma
coactivator 1 alpha, PGC1alpha; retinoid X receptor gamma, RXRgamma; and retinoic
acid receptor alpha, RARalpha) gene expression of breeding hens and chicks. In
experiment 1, 432 hens were divided into three groups and fed diets supplemented
with 0 (as control group), 20 or 40 mg/kg xanthophylls. Blood was sampled at 7,
14, 21, 28 and 35 days of trial. Liver, duodenum, jejunum and ileum were sampled
at 35 days of trial. Results showed that serum HDLC level of hens was increased
after dietary 40 mg/kg xanthophyll addition for 21, 28 and 35 days, while serum
TG, CHO and LDLC were not affected. Xanthophyll addition also increased PPARgamma
expression in jejunum, RXRgamma expression in duodenum and jejunum, and RARalpha
expression in liver and duodenum. Experiment 2 was a 2 * 2 factorial design. Male
chicks hatched from 0 or 40 mg/kg xanthophyll diet of hens were fed diet
containing either 0 or 40 mg/kg xanthophylls. Liver, duodenum, jejunum and ileum
were sampled at 0, 7, 14 and 21 days after hatching. Blood samples were also
collected at 21 days. Results showed that in ovo xanthophylls elevated PPARgamma
in duodenum and jejunum, and RXRgamma and RARalpha in liver of chicks mainly
within 1 week after hatching, while dietary xanthophylls increased serum HDLC
level and PPARgamma and RXRgamma in liver from 2 weeks onwards. In conclusion,
our research suggested xanthophylls can regulate serum lipid profile and nuclear
factor expression in hens and chicks.
PMID- 28503818
TI - Lidocaine for pain control during intrauterine device insertion.
AB - AIM: The aim of this study was to compare the effects of topical lidocaine spray,
cream and injection on pain perception during intrauterine device (IUD)
insertion. METHODS: Multiparous women of reproductive age were randomized into
control, lidocaine cream, spray and injection groups. A 10 cm visual analog scale
was used for all patients to evaluate pain during the three steps of the IUD
insertion procedure. Baseline pain assessment was made immediately after the
administration of analgesics, the second pain assessment was performed
immediately after use of the tenaculum, and the third pain assessment was
performed after IUD insertion. RESULTS: Two hundred patients were enrolled in the
study. The groups were similar in terms of demographic characteristics. The
lidocaine injection group exhibited higher baseline pain scores (P < 0.001). Pain
associated with tenaculum use was lower in the lidocaine spray group. Pain
related to IUD insertion was lower in the lidocaine spray and injection groups (P
< 0.001); however, lidocaine spray was superior to injection for the reduction of
IUD insertion related pain (P = 0.001). CONCLUSION: Lidocaine spray is a good
option for reducing the pain experienced during insertion of an IUD. It reduces
pain related to both tenaculum use and IUD insertion. Spray application is both
easy and rapid. Paracervical lidocaine injection also reduces pain during IUD
insertion, but has no effect on tenaculum-related pain; moreover, the injection
itself is painful. Therefore, this option is not a plausible method for reducing
pain during IUD insertion.
PMID- 28503819
TI - Nomenclature for factors of the HLA system, update March 2017.
PMID- 28503820
TI - The P2X7 receptor-NLRP3 inflammasome complex predicts the development of non
Hodgkin's lymphoma in Sjogren's syndrome: a prospective, observational, single
centre study.
AB - BACKGROUND: P2X7 receptor (P2X7R), trigger of acute inflammatory responses via
the NLRP3 inflammasome, is hyperfunctioning in patients with Sjogren's syndrome
(SS), where it stimulates IL-18 production. Some patients with SS develop a
mucosa-associated lymphoid tissue non-Hodgkin's lymphoma (MALT-NHL). OBJECTIVES:
To prospectively evaluate the involvement and the putative prognostic role of
this inflammatory pathway in the development of MALT-NHL. METHODS: A total of 147
women with SS have been prospectively followed for a mean of 52 months, relating
the expression and function of the P2X7R-inflammasome axis in salivary glands and
circulating lymphomonocytes to the prognosis and the degree of the disease.
RESULTS: At baseline, gene expression of P2X7R and of the inflammasome components
NLRP3, caspase-1 and IL-18 increased according to the presence of germinative
centres and was higher in autoantibody-positive individuals and strongly higher
in those developing a MALT-NHL over the follow-up. Glandular expression of IL-18
was threefold higher in MALT-NHL than in controls or in the other patients with
SS. P2X7R did not colocalize with generic markers of inflammatory infiltrate,
like CD20, being selectively expressed by epithelial cells. P2X4R, sharing
functional characteristics with P2X7R, did not differ in SS and controls. The
increased P2X7R gene and protein expression was tissue specific, no difference
being observed in peripheral lymphomonocytes between SS with MALT-NHL and SS not
developing MALT-NHL. CONCLUSION: We propose the P2X7R-inflammasome axis as a
novel potential pathway involved in both SS exocrinopathy and lymphomagenesis,
reinforcing the hypothesis of a key role of IL-18, via its increased P2X7R
mediated production, in the pathogenesis of lymphoproliferative malignancies, and
opening novel opportunities for the early diagnosis of lymphoproliferative
complications and the development of potential targeted therapies.
PMID- 28503822
TI - Constitutional mismatch repair deficiency in a healthy child: On the spot
diagnosis?
AB - Constitutional mismatch repair deficiency (CMMRD) is a rare, recessively
inherited childhood cancer predisposition syndrome caused by biallelic germline
mutations in one of the mismatch repair genes. The CMMRD phenotype overlaps with
that of neurofibromatosis type 1 (NF1), since many patients have multiple cafe-au
lait macules (CALM) and other NF1 signs, but no germline NF1 mutations. We report
of a case of a healthy 6-year-old girl who fulfilled the diagnostic criteria of
NF1 with >6 CALM and freckling. Since molecular genetic testing was unable to
confirm the diagnosis of NF1 or Legius syndrome and the patient was a child of
consanguineous parents, we suspected CMMRD and found a homozygous PMS2 mutation
that impairs MMR function. Current guidelines advise testing for CMMRD only in
cancer patients. However, this case illustrates that including CMMRD in the
differential diagnosis in suspected sporadic NF1 without causative NF1 or SPRED1
mutations may facilitate identification of CMMRD prior to cancer development. We
discuss the advantages and potential risks of this CMMRD testing scenario.
PMID- 28503821
TI - Effects of continuous low dose infusion of lipopolysaccharide on inflammatory
responses, milk production and milk quality in dairy cows.
AB - The objective of this study was to evaluate the effects of continuous low dose
infusion of lipopolysaccharide (LPS) on inflammatory responses and milk
production and quality in lactating dairy cows. Eight Holstein cows were assigned
to two treatments in a cross-over experimental design. Cows were infused
intravenously either with saline solution or with saline solution containing LPS
from Escherichia coli O111:B4 at a dose of 0.01 MUg LPS/kg body weight for
approximately 6 hr each day during a seven-day trial. The clinical symptoms and
milk production performance were observed. Milk samples were analysed for
conventional components, fatty acids and amino acids. And jugular vein and
mammary vein plasma samples were analysed for concentrations of cytokines and
acute phase proteins. LPS infusion decreased feed intake and milk yield. An
increase in body temperature was observed after LPS infusion. LPS infusion also
increased plasma concentrations of interleukin-1beta, serum amyloid A, LPS
binding protein, C-reactive protein and haptoglobin. LPS infusion decreased the
contents of some fatty acids, such as C17:1, C18:0, C18:1n9 (trans) and C18:2n6
(trans), and most amino acids except for methionine, threonine, histidine,
cysteine, tyrosine and proline in the milk. The results indicated that a
continued low dose infusion of LPS can induce an inflammatory response, decrease
milk production and reduce milk quality.
PMID- 28503824
TI - An index to predict asthma in wheezing young children produced promising initial
results.
PMID- 28503823
TI - Impact of surgery on survival in stage IV breast cancer.
PMID- 28503825
TI - New insights into Ca2+ channel function in health and disease.
PMID- 28503826
TI - Prospective randomized trial of neoadjuvant chemotherapy during the 'wait period'
following preoperative chemoradiotherapy for rectal cancer: results of the WAIT
trial.
AB - AIM: The aim was to determine whether the addition of additional cycles of
chemotherapy during the 'wait period' following neoadjuvant chemoradiotherapy for
rectal cancer improves the pathological complete response (pCR) rate. METHOD:
Rectal cancer patients were randomly allocated either to a standard 10 week wait
period before surgery (standard chemoradiotherapy, SCRT) or to receive three
cycles of fluorouracil based chemotherapy following chemoradiotherapy during a
similar 10 week wait (extended chemoradiotherapy, XCRT). The primary end-point
was pCR as determined by blinded pathological assessment. RESULTS: Forty-nine
patients were randomized (SCRTn = 24, XCRTn = 25). pCR occurred in 10 patients
overall but there was no significant difference in pCR between the groups (SCRTn
= 6, XCRTn = 4, P = 0.49). CONCLUSION: The addition of three cycles of 5
fluorouracil/leucovorin in a 10 week wait period after conventional
chemoradiotherapy seems to result in similar pCR rates in patients with locally
advanced rectal cancer based on this small randomized trial.
PMID- 28503827
TI - Comparison of non-invasive tear film stability measurement techniques.
AB - BACKGROUND: Measurement of tear film stability is commonly used to give an
indication of tear film quality but a number of non-invasive techniques exists
within the clinical setting. This study sought to compare three non-invasive tear
film stability measurement techniques: instrument-mounted wide-field white light
clinical interferometry, instrument-mounted keratoscopy and hand-held
keratoscopy. METHODS: Twenty-two subjects were recruited in a prospective,
randomised, masked, cross-over study. Tear film break-up or thinning time was
measured non-invasively by independent experienced examiners, with each of the
three devices, in a randomised order, within an hour. RESULTS: Significant
correlation was observed between instrument-mounted interferometric and
keratoscopic measurements (p < 0.001) but not between the hand-held device and
the instrument-mounted techniques (all p > 0.05). Tear film stability values
obtained from the hand-held device were significantly shorter and demonstrated
narrower spread than the other two instruments (all p < 0.05), while no
significant differences were observed between the two instrument-mounted devices
(all p > 0.05). CONCLUSION: Good clinical agreement exists between the instrument
mounted interferometric and keratoscopic measurements but not between the hand
held device and either of the instrument-mounted techniques. The results
highlight the importance of specifying the instrument employed to record non
invasive tear film stability.
PMID- 28503828
TI - Birthweight and cardiovascular risk factors in a Japanese general population.
AB - AIM: This study was conducted to examine whether babies born small develop
cardiovascular problems in later life. METHODS: Data were examined
retrospectively for 1241 city dwellers (men 521, women 720) aged 40-69 years who
received a medical examination at a single institution. Blood tests, physical
measurements, and a questionnaire survey regarding birth weight (small, medium,
large), medication history and lifestyle (alcohol consumption, smoking, exercise)
was administered. We selected 28 persons (12 men and 16 women) from and studied
the rate of conformity between the participants' memory (small, medium, large)
and the actual birth weight recorded in their maternal and child health handbook
(< 2500, 2500-3500, > 3500 g). RESULTS: Participants' recall of their birth
weight correlated well with the weight recorded in the maternal notebook (r =
0.73; P < 0.025). Low-density lipoprotein (P < 0.05), and total cholesterol (P <
0.01) levels in men, and systolic (P < 0.05) and diastolic (P < 0.05) blood
pressure in women were significantly inversely related to birth weight when
controlling for age, body mass index, medication, and lifestyle. The percentage
of women born small, medium, and large taking antidiabetic agents was 17.8%, 2.9%
and 0% (P < 0.05), respectively. CONCLUSION: A low birth weight was associated
with high low-density lipoprotein and total cholesterol levels in men, and
hypertension and diabetes mellitus in women aged 40-69.
PMID- 28503829
TI - Unravelling seed dispersal through fragmented landscapes: Frugivore species
operate unevenly as mobile links.
AB - Seed dispersal constitutes a pivotal process in an increasingly fragmented world,
promoting population connectivity, colonization and range shifts in plants.
Unveiling how multiple frugivore species disperse seeds through fragmented
landscapes, operating as mobile links, has remained elusive owing to
methodological constraints for monitoring seed dispersal events. We combine for
the first time DNA barcoding and DNA microsatellites to identify, respectively,
the frugivore species and the source trees of animal-dispersed seeds in forest
and matrix of a fragmented landscape. We found a high functional complementarity
among frugivores in terms of seed deposition at different habitats (forest vs.
matrix), perches (isolated trees vs. electricity pylons) and matrix sectors
(close vs. far from the forest edge), cross-habitat seed fluxes, dispersal
distances and canopy-cover dependency. Seed rain at the landscape-scale, from
forest to distant matrix sectors, was characterized by turnovers in the
contribution of frugivores and source-tree habitats: open-habitat frugivores
replaced forest-dependent frugivores, whereas matrix trees replaced forest trees.
As a result of such turnovers, the magnitude of seed rain was evenly distributed
between habitats and landscape sectors. We thus uncover key mechanisms behind
"biodiversity-ecosystem function" relationships, in this case, the relationship
between frugivore diversity and landscape-scale seed dispersal. Our results
reveal the importance of open-habitat frugivores, isolated fruiting trees and
anthropogenic perching sites (infrastructures) in generating seed dispersal
events far from the remnant forest, highlighting their potential to drive
regeneration dynamics through the matrix. This study helps to broaden the "mobile
link" concept in seed dispersal studies by providing a comprehensive and
integrative view of the way in which multiple frugivore species disseminate seeds
through real-world landscapes.
PMID- 28503830
TI - Synthetic OCP heterodimers are photoactive and recapitulate the fusion of two
primitive carotenoproteins in the evolution of cyanobacterial photoprotection.
AB - The orange carotenoid protein (OCP) governs photoprotection in the majority of
cyanobacteria. It is structurally and functionally modular, comprised of a C
terminal regulatory domain (CTD), an N-terminal effector domain (NTD) and a
ketocarotenoid; the chromophore spans the two domains in the ground state and
translocates fully into the NTD upon illumination. Using both the canonical OCP1
from Fremyella diplosiphon and the presumably more primitive OCP2 paralog from
the same organism, we show that an NTD-CTD heterodimer forms when the domains are
expressed as separate polypeptides. The carotenoid is required for the
heterodimeric association, assembling an orange complex which is stable in the
dark. Both OCP1 and OCP2 heterodimers are photoactive, undergoing light-driven
heterodimer dissociation, but differ in their ability to reassociate in darkness,
setting the stage for bioengineering photoprotection in cyanobacteria as well as
for developing new photoswitches for biotechnology. Additionally, we reveal that
homodimeric CTD can bind carotenoid in the absence of NTD, and name this
truncated variant the C-terminal domain-like carotenoid protein (CCP). This
finding supports the hypothesis that the OCP evolved from an ancient fusion event
between genes for two different carotenoid-binding proteins ancestral to the NTD
and CTD. We suggest that the CCP and its homologs constitute a new family of
carotenoproteins within the NTF2-like superfamily found across all kingdoms of
life.
PMID- 28503831
TI - Can Neuroscience Contribute to Practical Ethics? A Critical Review and Discussion
of the Methodological and Translational Challenges of the Neuroscience of Ethics.
AB - Neuroethics is an interdisciplinary field that arose in response to novel ethical
challenges posed by advances in neuroscience. Historically, neuroethics has
provided an opportunity to synergize different disciplines, notably proposing a
two-way dialogue between an 'ethics of neuroscience' and a 'neuroscience of
ethics'. However, questions surface as to whether a 'neuroscience of ethics' is a
useful and unified branch of research and whether it can actually inform or lead
to theoretical insights and transferable practical knowledge to help resolve
ethical questions. In this article, we examine why the neuroscience of ethics is
a promising area of research and summarize what we have learned so far regarding
its most promising goals and contributions. We then review some of the key
methodological challenges which may have hindered the use of results generated
thus far by the neuroscience of ethics. Strategies are suggested to address these
challenges and improve the quality of research and increase neuroscience's
usefulness for applied ethics and society at large. Finally, we reflect on
potential outcomes of a neuroscience of ethics and discuss the different
strategies that could be used to support knowledge transfer to help different
stakeholders integrate knowledge from the neuroscience of ethics.
PMID- 28503832
TI - The Voluntary Nature of Decision-Making in Addiction: Static Metaphysical Views
Versus Epistemologically Dynamic Views.
AB - The degree of autonomy present in the choices made by individuals with an
addiction, notably in the context of research, is unclear and debated. Some have
argued that addiction, as it is commonly understood, prevents people from having
sufficient decision-making capacity or self-control to engage in choices
involving substances to which they have an addiction. Others have criticized this
position for being too radical and have counter-argued in favour of the full
autonomy of people with an addiction. Aligning ourselves with middle-ground
positions between these two extremes, we flesh out an account of voluntary action
that makes room for finer-grained analyses than the proposed all-or-nothing
stances, which rely on a rather static metaphysical understanding of the nature
of the voluntariness of action. In contrast, a dynamic concept of voluntary
action better accounts for varying levels of voluntariness of the person with an
addiction which takes into consideration internal (e.g. cravings) and external
(e.g. perceptions of degrees of freedom related to different options)
determinants of choice. Accordingly, like other components of autonomous choices
such as level of information, voluntariness can fluctuate. Therefore, there are
important implications for research and clinical ethics in matters of consent,
recruitment, and therapeutic approaches. Overall, our proposal is inspired by a
pragmatist understanding of voluntary action, notably with respect to how
voluntariness is both informed by actions and experiences that shape one's view
of the world.
PMID- 28503833
TI - Moral Enhancement Meets Normative and Empirical Reality: Assessing the Practical
Feasibility of Moral Enhancement Neurotechnologies.
AB - Moral enhancement refers to the possibility of making individuals and societies
better from a moral standpoint. A fierce debate has emerged about the ethical
aspects of moral enhancement, notably because steering moral enhancement in a
particular direction involves choosing amongst a wide array of competing options,
and these options entail deciding which moral theory or attributes of the moral
agent would benefit from enhancement. Furthermore, the ability and effectiveness
of different neurotechnologies to enhance morality have not been carefully
examined. In this paper, we assess the practical feasibility of moral enhancement
neurotechnologies. We reviewed the literature on neuroscience and cognitive
science models of moral judgment and analyzed their implications for the specific
target of intervention (cognition, volition or affect) in moral enhancement. We
also reviewed and compared evidence on available neurotechnologies that could
serve as tools of moral enhancement. We conclude that the predictions of
rationalist, emotivist, and dual process models are at odds with evidence, while
different intuitionist models of moral judgment are more likely to be aligned
with it. Furthermore, the project of moral enhancement is not feasible in the
near future as it rests on the use of neurointerventions, which have no moral
enhancement effects or, worse, negative effects.
PMID- 28503834
TI - Respect for Autonomy in Light of Neuropsychiatry.
AB - Bioethics needs an elaborated concept of autonomy based on empirical knowledge
about the prerequisites of the capacity of autonomy. Whereas Beauchamp and
Childress, and many other bioethicists have discussed social influences on the
capacity of autonomy in depth, neurobiological influences have received less
attention. A comprehensive concept of autonomy should consider both social and
biological factors that can diminish the capacity of autonomy. This article
focuses on neurobiological influences that can reduce the capacity of autonomy.
The thesis of this article is that the integration of neuropsychiatric knowledge
into the concept of autonomy is essential for (1) evaluating demands for harmful
medical treatments which might be caused by a brain disease, and (2) deciding on
involuntary treatments of patients who suffer from substantial lack of autonomy
due to neuropsychiatric disorders. Diametrically opposed to such a comprehensive
concept of the capacity of autonomy is the concept of 'liberty of illness'. In
Germany, this concept is supported not only by anti-psychiatric groups but also
by the Federal Constitutional Court. Several real cases demonstrate how the brain
can be 'hijacked' by parasites, antibodies or technical devices. Applying the
concept of 'liberty of illness' to persons whose decision-making capacity is
severely affected by neuropsychiatric disorders is cynical. These patients
neither chose their disease nor would refuse effective treatment if their will
was not disturbed by the disease. Respect for autonomy should be understood as
the positive obligation to save, support or restore the biological prerequisites
of the capacity for autonomous decision-making.
PMID- 28503835
TI - Neuroethics: Neuroscience's Contributions to Bioethics.
PMID- 28503836
TI - Role of anticholinergic burden in primary care patients with first cognitive
complaints.
AB - BACKGROUND AND PURPOSE: Drugs with anticholinergic properties might have a
negative impact on cognition, but findings are still conflicting. The association
was evaluated between anticholinergic drugs and cognitive performance in primary
care patients with first cognitive complaints. METHODS: From April 2013 to March
2014, 353 general practitioners administered the Mini-Mental State Examination
(MMSE) to patients presenting with first cognitive complaints. Drug history was
collected and the anticholinergic cognitive burden (ACB) was scored and
categorized as ACB 0, ACB 1 and ACB 2+. A mixed effect linear regression model
was used to assess the association between ACB and MMSE score. RESULTS: Of 4249
subjects entering the study (mean age 77 +/- 8.2 years, 66.4% women and mean
years of schooling 8.9 +/- 4.5), 25.8% received at least one drug with
anticholinergic action. According to multivariate analysis, and after adjustment
for several confounders, subjects with ACB 2+ had a statistically significant
lower MMSE score compared with those with ACB 0 (beta -0.63; 95% confidence
interval -1.19; -0.07). Subjects with ACB 1 had a non-statistically significant
lower MMSE score than those with ACB 0 (beta -0.11; 95% confidence interval
0.37; 0.15). CONCLUSIONS: Anticholinergic medication might affect cognitive
function in people with first cognitive complaints. Alternatives should be taken
into account when possible, balancing the benefits and harms of these
medications.
PMID- 28503839
TI - Introduction to the Special Issue on Proteases and Proteolysis in Health and
Disease.
AB - This Special Issue on Proteases and Proteolysis in Health and Disease comprises
11 reviews that cover a broad range of topics in this diverse field. We hope you
find these pieces as engaging and informative as we have and we are grateful to
their authors for taking the time to write for The FEBS Journal.
PMID- 28503837
TI - Efficacy of protocol-based pharmacotherapy management on anticoagulation with
warfarin for patients with cardiovascular surgery.
AB - WHAT IS KNOWN AND OBJECTIVE: Anticoagulation therapy with warfarin requires
periodic monitoring of prothrombin time-international normalized ratio (PT-INR)
and adequate dose adjustments based on the data to minimize the risk of bleeding
and thromboembolic events. In our hospital, we have developed protocol-based
pharmaceutical care, which we called protocol-based pharmacotherapy management
(PBPM), for warfarin therapy. The protocol requires pharmacists to manage timing
of blood sampling for measuring PT-INR and warfarin dosage determination based on
an algorithm. This study evaluated the efficacy of PBPM in warfarin therapy by
comparing to conventional pharmaceutical care. METHODS: From October 2013 to June
2015, a total of 134 hospitalized patients who underwent cardiovascular surgeries
received post-operative warfarin therapy. The early series of patients received
warfarin therapy as the conventional care (control group, n=77), whereas the
latter received warfarin therapy based on the PBPM (PBPM group, n=68). These
patients formed the cohort of the present study and were retrospectively
analysed. RESULTS: The indications for warfarin included aortic valve replacement
(n=56), mitral valve replacement (n=4), mitral valve plasty (n=22) and atrial
fibrillation (n=29). There were no differences in patients' characteristics
between both groups. The percentage time in therapeutic range in the first 10
days was significantly higher in the PBPM group (47.1%) than that in the control
group (34.4%, P<.005). The average time to reach the steady state was
significantly (P<.005) shorter in the PBPM group compared to the control group
(7.3 vs 8.6 days). WHAT IS NEW AND CONCLUSION: Warfarin therapy based on our
novel PBPM was clinically safe and resulted in significantly better
anticoagulation control compared to conventional care.
PMID- 28503840
TI - A Critical Note on Treatment of a Severe Diltiazem Intoxication: High-Dose
Calcium and Glucagon Infusions.
AB - The morbidity and mortality of a severe calcium channel blocker intoxication is
high due to serious toxic cardiac effects. Its treatment is supported by low
quality evidence from the heterogeneous literature. We describe a case of a
severe diltiazem intoxication and critically appraise the efficacy and role of
high-dose calcium and glucagon infusions. A 53-year-old woman was admitted to the
emergency department with a cardiogenic shock with complete AV block, not
responding to atropine, isoprenaline and an external pacemaker. Later on, it
became clear that she had a severe diltiazem intoxication which was successfully
treated with isotone fluids, inotropes, vasopressors and continuous infusion of
high-dose calcium and glucagon. The patient developed, however, an acute,
necrotizing pancreatitis, probably related to iatrogenic high calcium levels.
This case demonstrates lack of consensus regarding target levels of serum calcium
for treatment of a severe diltiazem intoxication. Goal-directed tapering of
calcium should prevent side effects of iatrogenic hypercalcaemia. The
contribution of glucagon infusions is doubtful due to the instability of
solubilized glucagon. This might explain why the effect of glucagon is variable
in the literature.
PMID- 28503841
TI - Social networks of adults with an intellectual disability from South Asian and
White communities in the United Kingdom: A comparison.
AB - BACKGROUND: Little research exists comparing the social networks of people with
intellectual disability (ID) from South Asian and White backgrounds. This UK
study reports on the barriers that South Asian people with intellectual
disability face in relation to social inclusion compared to their White
counterparts. MATERIALS AND METHODS: A mixed-methods research design was adopted
to explore the social lives of 27 men (15 White; 12 South Asian) and 20 women (10
White; 10 South Asian with intellectual disability). Descriptive and parametric
tests were used to analyse the quantitative data. RESULTS: The average network
size of the whole group was 32 members. South Asian participants had more family
members whilst White participants had more service users and staff in their
networks; 96% network members from White intellectual disability group were also
of White background, whilst the South Asian group had mixed ethnic network
members. CONCLUSIONS: Social networks of individuals with intellectual disability
in this study were found to be larger overall in comparison with previous
studies, whilst network structure differed between the White and South Asian
population. These differences have implications relating to future service
planning and appropriateness of available facilities.
PMID- 28503842
TI - Demographic histories of three predatory lady beetles reveal complex patterns of
diversity and population size change in the United States.
AB - Predatory lady beetles (Coccinellidae) contribute to biological control of
agricultural pests, however, multiple species frequently compete for similar
resources in the same environment. Numerous studies have examined ecological
interactions among the native North American convergent lady beetle (Hippodamia
convergens) and two introduced species, the seven-spotted lady beetle (Coccinella
septempunctata) and the Asian lady beetle (Harmonia axyridis), in agricultural
fields and described multiyear population dynamics. However, the evolutionary
dynamics of these interacting species of predatory beetles are uncharacterized.
We utilize publicly available multilocus genotype data from geographically
disjunct populations of these three species to estimate demography across North
American populations. Coalescent analyses reveal (1) a recent (~4-5 years)
decline (>12 fold) in microsatellite effective population size of H. convergens,
while expanding (mutation scaled growth rate in 1/u generations = 2910, SD = 362)
over evolutionary time scales, (2) a massive (>150 fold), and very recent,
effective population size decline in Ha. axyridis, and (3) population size growth
(mutation scaled growth rate = 997, SD = 60) over recent and evolutionary time
scales in C. septempunctata. Although these estimates are based on genetic data
with different mutation rates and patterns of inheritance (mitochondrial versus
nuclear), these dynamic and differing population size histories are striking.
Further studies of the interactions of these predatory lady beetles in the field
are thus warranted to explore the consequences of population size change and
biological control activities for evolutionary trajectories in North America.
PMID- 28503843
TI - The volume, cost and outcomes of pancreatic resection in a regional centre in New
Zealand.
AB - BACKGROUND: The frequency, costs and outcome of pancreatic resection (both
pancreaticoduodenectomy and distal pancreatectomy) were reviewed in our own
institution and correlated with regional population growth as well as national
resection rates and locations. METHODS: Demographic, pathological and outcome
data on pancreaticoduodenectomy and distal pancreatectomy were obtained from a
prospectively maintained database for the years 2005-2009 and 2010-2014. During
this period, the catchment population grew from 460 000 to 567 000. Costing
information was obtained from the hospital-independent costing and coding
committee, and the locations and rates of pancreatic resection were obtained by
interrogating the national minimum dataset. RESULTS: A total of 41
pancreatectomies (29 pancreaticoduodenectomy, 12 distal pancreatectomy) were
performed between 2005 and 2009, increasing to 84 pancreatectomies (55
pancreaticoduodenectomies, 27 distal pancreatectomies and two total
pancreatectomies) between 2010 and 2014. This constituted one sixth of the
national volume of pancreatic resections. There was no difference in patient
demographics or indications for resection between the two time periods; however,
portal vein resection was used more frequently in the second period. Margin
positivity rate decreased (7 of 41 versus 8 of 84) and lymph node harvest
increased (median 8 nodes versus median 15 nodes) between the two time periods.
Overall 30-day mortality was 1.6%. CONCLUSION: In New Zealand, regional rates of
pancreatic resection reflect regional population demands, and institutional
growth is driven by local population requirements. Institutional growth can be
achieved with the maintenance of internationally accepted outcomes and quality
indicators.
PMID- 28503845
TI - The specificity of the neural response to speech at birth.
AB - In this work we ask whether at birth, the human brain responds uniquely to
speech, or if similar activation also occurs to a non-speech surrogate
'language'. We compare neural activation in newborn infants to the language heard
in utero (English), to an unfamiliar language (Spanish), and to a whistled
surrogate language (Silbo Gomero) that, while used by humans to communicate, is
not speech. Anterior temporal areas of the neonate cortex are activated in
response to both familiar and unfamiliar spoken language, but these classic
language areas are not activated to the whistled surrogate form. These results
suggest that at the time human infants emerge from the womb, the neural
preparation for language is specialized to speech.
PMID- 28503844
TI - TypeLoader: A fast and efficient automated workflow for the annotation and
submission of novel full-length HLA alleles.
AB - Recent years have seen a rapid increase in the discovery of novel allelic
variants of the human leukocyte antigen (HLA) genes. Commonly, only the exons
encoding the peptide binding domains of novel HLA alleles are submitted. As a
result, the IPD-IMGT/HLA Database lacks sequence information outside those
regions for the majority of known alleles. This has implications for the
application of the new sequencing technologies, which deliver sequence data often
covering the complete gene. As these technologies simplify the characterization
of the complete gene regions, it is desirable for novel alleles to be submitted
as full-length sequences to the database. However, the manual annotation of full
length alleles and the generation of specific formats required by the sequence
repositories is prone to error and time consuming. We have developed TypeLoader
to address both these facets. With only the full-length sequence as a starting
point, Typeloader performs automatic sequence annotation and subsequently handles
all steps involved in preparing the specific formats for submission with very
little manual intervention. TypeLoader is routinely used at the DKMS Life Science
Lab and has aided in the successful submission of more than 900 novel HLA alleles
as full-length sequences to the European Nucleotide Archive repository and the
IPD-IMGT/HLA Database with a 95% reduction in the time spent on annotation and
submission when compared with handling these processes manually. TypeLoader is
implemented as a web application and can be easily installed and used on a
standalone Linux desktop system or within a Linux client/server architecture.
TypeLoader is downloadable from http://www.github.com/DKMS-LSL/typeloader.
PMID- 28503846
TI - Tailored-made robotic abdominoperineal resection, using the da Vinci Xi, for a
regrowth of rectal tumour after complete clinical response - a video vignette.
PMID- 28503847
TI - Addition of Color Doppler Sonography for Detection of Amniotic Fluid Disturbances
and Its Implications on Perinatal Outcomes.
AB - OBJECTIVES: To determine whether color Doppler sonography increases the detection
of pregnancies at risk for adverse outcomes. METHODS: Participants admitted to
labor and delivery with the anticipation of a vaginal delivery underwent
measurements of amniotic fluid volume (AFV) using amniotic fluid index (AFI) and
single deepest pocket (SDP) techniques by grayscale followed by color Doppler
sonography. Oligohydramnios was defined as an AFI of less than 5 cm or an SDP of
less than 2 cm. Intrapartum and perinatal outcomes were compared between
participants with a diagnosis of a low AFV by grayscale and color Doppler
sonography. RESULTS: Over 42 months, 428 women were enrolled in the study. Color
Doppler sonography resulted in lower AFV estimates (mean +/- SD by the AFI, 10.7
+/- 3.7 cm by grayscale sonography and 8.6 +/- 3.6cm by color Doppler sonography;
P < .0001). For the SDP, the mean AFVs were 4.6 +/- 2.0 cm by grayscale
sonography and 3.4 +/- 1.4 cm by color Doppler sonography (P < .0001). The level
of agreement between grayscale and color Doppler sonography in estimating the AFV
was fair, with kappa = 0.32 for the AFI and 0.28 for the SDP. Outcome measures of
AFVs classified as low based on color Doppler sonography (normal by grayscale
sonography) and those classified as low by grayscale sonography (low by color
Doppler sonography) were compared. There was no difference in composite perinatal
complications, mode of delivery, or composite neonatal complications.
CONCLUSIONS: The use of color Doppler sonography leads to the overdiagnosis of
low AFVs and does not appear to increase the detection of pregnancies destined
for adverse intrapartum or perinatal outcomes.
PMID- 28503848
TI - In Response: Ultrasound-assisted Lumbar Puncture on Infants in the Pediatric
Emergency Department.
PMID- 28503849
TI - Meaning and object in Freud's theory of language.
AB - This article sets out to challenge the interpretation of Freud's views on the
origins of the meaning of language according to which meaning always originates
from an act of naming. In Freud's terms, word-presentations would originally
denote object- or thing-presentations and gain meaning through this reference.
This interpretation claims that this view was already expressed in Freud's On
Aphasia (1891) and influenced all his later theory of language. To oppose this
claim, three conceptions proposed by Freud are discussed that strongly suggest
the participation of language in the construction of the field of objects: a
metapsychological hypothesis (the concepts of word-, thing-, and object
presentation), the explanation of a psychopathological phenomenon (the genesis of
a fetishistic object-choice), and a concept concerning the foundations of the
psychoanalytic method of dream interpretation (secondary elaboration). As a
conclusion, it is argued that Freud's early views in On Aphasia (1891) can be
alternatively understood such as to allow for a different view of language and
its relationship with objects.
PMID- 28503850
TI - Roles of spermine in modulating the antioxidant status and Nrf2 signalling
molecules expression in the thymus and spleen of suckling piglets-new insight.
AB - This study aimed to investigate the effects of spermine and extended spermine
administration on the antioxidant status and expression of NF-E2-related factor 2
(Nrf2) signalling molecules in the thymus and spleen in suckling piglets. One
half of eighty 12-day-old suckling piglets obtained sufficient nutrient intake
supplemented with spermine (0.4 mmol/kg body weight), and another half received
restricted nutrient intake supplemented with physiological saline in equal doses
once a day for 7 hr or 3, 6 or 9 days in pairs. Spermine supplementation and its
extended duration significantly decreased malondialdehyde (MDA) and protein
carbonyl (PC) contents (p < .05), but markedly improved antisuperoxide anion
(ASA), antihydroxyl radical (AHR), catalase (CAT), total superoxide dismutase (T
SOD), total antioxidant capacity (T-AOC), glutathione peroxidase (GPx) and
glutathione-S-transferase (GST) activities (p < .05) and glutathione (GSH)
content (p < .05) in the thymus and spleen. Additionally, real-time PCR analysis
showed that spermine administration and extended spermine intake reduced Kelch
like ECH-associated protein 1 (Keap1) gene transcription and enhanced SOD1, GPx1,
CAT, glutathione reductase (GR) and Nrf2 mRNA levels of the thymus and spleen (p
< .05), and also improved GST gene expression in the thymus (p < .05). Notably,
the spermine-supplemented time for the optimal effects of suckling piglet was
determined to be 6 days. Collectively, the current study suggested that spermine
supplementation and extended spermine administration could protect the health of
the thymus and spleen from early weaning by enhancing the antioxidant status and
regulating the expression of antioxidant-related signalling molecules.
PMID- 28503851
TI - Characterizing bacterial communities in paper production-troublemakers revealed.
AB - Biofilm formation is a major cause of reduced paper quality and increased down
time during paper manufacturing. This study uses Illumina next-generation
sequencing to identify the microbial populations causing quality issues due to
their presence in biofilms and slimes. The paper defects investigated contained
traces of the films and/or slime of mainly two genera, Tepidimonas and
Chryseobacterium. The Tepidimonas spp. found contributed on average 68% to the
total bacterial population. Both genera have been described previously to be
associated with biofilms in paper mills. There was indication that Tepidimonas
spp. were present as compact biofilm in the head box of one paper machine and was
filtered out by the paper web during production. On the other hand Tepidimonas
spp. were also present to a large extent in the press and white waters of two
nonproblematic paper machines. Therefore, the mere presence of a known biofilm
producer alone is not sufficient to cause slimes and therefore paper defects and
other critical factors are additionally at play. For instance, we identified
Acidovorax sp., which is an early colonizer of paper machines, exhibiting the
ability to form extracellular DNA matrices for attachment and biofilm formation.
PMID- 28503853
TI - Glucuronidation and its impact on the bioactivity of [6]-shogaol.
AB - SCOPE: -shogaol (6S) from ginger has been reported to have diverse bioactivities
and can be widely metabolized in animals and humans; however, the impact of
glucuronidation on its bioactivity is still largely unknown. This study
investigates the glucuronidation of 6S and its effect on cell cytotoxicity and
Nrf2-inducing activities of 6S. METHODS AND RESULTS: The glucuronidated
metabolite of 6S, 4-O-monoglucuronide 6S (6S-G), was synthesized and
characterized for the first time. Glucuronidation of 6S in humans was studied
using microsomes of the liver and intestine and recombinant UDP
glucuronosyltransferase (UGTs). The kinetics of 6S glucuronidation by human liver
and intestinal microsomes followed the substrate inhibition kinetics model. The
intrinsic glucuronidation clearance (CLint ) of 6S in human liver microsomes was
higher than that in human intestine microsomes. Among the recombinant UGTs
examined, UGT1A1, 1A3, 1A6, 1A8, 1A10, 2B7, 2B15, and 2B17 exhibited
glucuronidation activity toward 6S, with UGT2B7 being the most potent one.
Compared with 6S, the glucuronidation of 6S largely eliminated its cell
cytotoxicity against human colon cancer cell lines HT-116 and HT-29, and its Nrf2
inducing activity. CONCLUSION: The findings from current study provide
foundations for understanding the role of glucuronidation in biotransformation
and biological activities of 6S.
PMID- 28503855
TI - Mechanical optic neuropathy in high myopia.
PMID- 28503854
TI - Nomenclature for factors of the HLA system, updated on January 2017.
PMID- 28503852
TI - Smoking-associated morbidities on computed tomography lung cancer screens in HIV
infected smokers.
PMID- 28503856
TI - Pyrazolo[4,3-h]quinoline Ligand-Based Iridium(III) Complexes for
Electrochemiluminescence.
AB - Electrochemiluminescence (ECL) based on [Ru(bpy)3 ]2+ systems is widely utilized
for immunoassays. In order to extend the promising potential of ECL-based
applications, IrIII complexes have recently attracted attention as probes because
of their excellent luminescent properties and tunable emission wavelength. Here
we describe a series of Ir complexes using a large pi-conjugated ligand and
different ancillary chelates. The complexes synthesized have been chemically and
spectroscopically characterized and used for ECL measurements with annihilation
and co-reactant methods. One of the IrIII complexes investigated exhibits the
brightest, ever reported, ECL efficiency in acetonitrile employing the benzoyl
peroxide (BPO) co-reactant method.
PMID- 28503857
TI - Recent developments in structural studies on acetylcholinesterase.
AB - This review focuses on several recent developments concerning structure-function
relationships in vertebrate acetylcholinesterase. These include studies on high
resolution structures of human acetylcholinesterase and its complexes; the first
crystal structure of a snake venom acetylcholinesterase, in which open and closed
states of the 'back door' are visualized; a powerful algorithm for redesigning
proteins for enhanced expression in prokaryotic systems, as applied to human
acetylcholinesterase, which has hitherto been an intractable target; in situ
implementation of 'click chemistry' in crystalline acetylcholinesterase, which
yields novel insights into the steric and dynamic changes involved in the
reaction within the active-site gorge; and a study that demonstrates the effect
of crystallization conditions on ligand alignment within a protein complex, in
this case the methylene blue-Torpedo californica acetylcholinesterase complex,
which highlights the relevance of the precipitant employed to structure-based
drug design. This is an article for the special issue XVth International
Symposium on Cholinergic Mechanisms.
PMID- 28503859
TI - Principles for being theoretical-Increasing the impact of research conducted in
primary care.
AB - Primary care is a unique research environment and is difficult to study well
without disrupting the delivery of care. Recent developments in implementation
and care delivery sciences have facilitated real world tests of interventions.
However primary care research often misses a foundational component of quality -
"being theoretical." Using cancer prevention and control as an example, this
commentary advocates for the imperative of using theory to guide research and
describes three principles for being theoretical. These principles, readily
amenable to clinical settings, will produce studies that do more than answer "did
it work?" and therefore increase the impact of primary care-based research across
the cancer continuum.
PMID- 28503858
TI - LdtR is a master regulator of gene expression in Liberibacter asiaticus.
AB - Huanglongbing or citrus greening disease is causing devastation to the citrus
industry. Liberibacter asiaticus, an obligate intracellular pathogen of citrus,
is one the causative agents of the disease. Most of the knowledge about this
bacterium has been deduced from the in silico exploration of its genomic
sequence. L. asiaticus differentially expresses genes during its transmission
from the psyllid vector, Diaphorina citri, to the plant. However, the regulatory
mechanisms for the adaptation of the bacterium into either hosts remain unknown.
Here we show that LdtR, a MarR family transcriptional regulator, activates or
represses transcription genome-wide. We performed a double approach to identify
the components of the LdtR regulon: a transcriptome analysis in both the related
bacterium Liberibacter crescens and citrus-infected leaves, strengthened with an
in silico prediction of LdtR regulatory sites. Our results demonstrated that LdtR
controls the expression of nearly 180 genes in L. asiaticus, distributed in
processes such as cell motility, cell wall biogenesis, energy production, and
transcription. These results provide new evidence about the regulatory network of
L. asiaticus, where the differential expression of genes from these functional
categories could be of great importance during the adaptation of the bacterium to
either hosts.
PMID- 28503861
TI - Estimates of subgroup treatment effects in overall nonsignificant trials: To what
extent should we believe in them?
AB - In drug development, it sometimes occurs that a new drug does not demonstrate
effectiveness for the full study population but appears to be beneficial in a
relevant subgroup. In case the subgroup of interest was not part of a
confirmatory testing strategy, the inflation of the overall type I error is
substantial and therefore such a subgroup analysis finding can only be seen as
exploratory at best. To support such exploratory findings, an appropriate
replication of the subgroup finding should be undertaken in a new trial. We
should, however, be reasonably confident in the observed treatment effect size to
be able to use this estimate in a replication trial in the subpopulation of
interest. We were therefore interested in evaluating the bias of the estimate of
the subgroup treatment effect, after selection based on significance for the
subgroup in an overall "failed" trial. Different scenarios, involving continuous
as well as dichotomous outcomes, were investigated via simulation studies. It is
shown that the bias associated with subgroup findings in overall nonsignificant
clinical trials is on average large and varies substantially across plausible
scenarios. This renders the subgroup treatment estimate from the original trial
of limited value to design the replication trial. An empirical Bayesian shrinkage
method is suggested to minimize this overestimation. The proposed estimator
appears to offer either a good or a conservative correction to the observed
subgroup treatment effect hence provides a more reliable subgroup treatment
effect estimate for adequate planning of future studies.
PMID- 28503860
TI - Epigenetic silencing of ADAMTS18 promotes cell migration and invasion of breast
cancer through AKT and NF-kappaB signaling.
AB - ADAMTS18 dysregulation plays an important role in many disease processes
including cancer. We previously found ADAMTS18 as frequently methylated tumor
suppressor gene (TSG) for multiple carcinomas, however, its biological functions
and underlying molecular mechanisms in breast carcinogenesis remain unknown.
Here, we found that ADAMTS18 was silenced or downregulated in breast cancer cell
lines. ADAMTS18 was reduced in primary breast tumor tissues as compared with
their adjacent noncancer tissues. ADAMTS18 promoter methylation was detected in
70.8% of tumor tissues by methylation-specific PCR, but none of the normal
tissues. Demethylation treatment restored ADAMTS18 expression in silenced breast
cell lines. Ectopic expression of ADAMTS18 in breast tumor cells resulted in
inhibition of cell migration and invasion. Nude mouse model further confirmed
that ADAMTS18 suppressed breast cancer metastasis in vivo. Further mechanistic
studies showed that ADAMTS18 suppressed epithelial-mesenchymal transition (EMT),
further inhibited migration and invasion of breast cancer cells. ADAMT18
deregulated AKT and NF-kappaB signaling, through inhibiting phosphorylation
levels of AKT and p65. Thus, ADAMTS18 as an antimetastatic tumor suppressor
antagonizes AKT and NF-kappaB signaling in breast tumorigenesis. Its methylation
could be a potential tumor biomarker for breast cancer.
PMID- 28503862
TI - Letter: hepatitis B virus reactivation in patients with chronic hepatitis C
during direct-acting anti-viral therapy.
PMID- 28503863
TI - Editorial: is it time for therapeutic drug monitoring of anti-TNF agents during
pregnancy? Maybe, maybe not.
PMID- 28503864
TI - Editorial: evidence is growing for protective effects of 5-aminosalicylates
against colitis-associated cancer-authors' reply.
PMID- 28503865
TI - Editorial: visceral fat as a predictor of post-operative recurrence of Crohn's
disease-Authors' reply.
PMID- 28503866
TI - Editorial: evidence is growing for protective effects of 5-aminosalicylates
against colitis-associated cancer.
PMID- 28503867
TI - Editorial: visceral fat as a predictor of post-operative recurrence of Crohn's
disease.
PMID- 28503868
TI - Editorial: is it time for therapeutic drug monitoring of anti-TNF agents during
pregnancy? Maybe, maybe not. Author's reply.
PMID- 28503869
TI - Letter: hepatitis B reactivation in patients with chronic hepatitis C during
direct-acting antiviral therapy-authors' reply.
PMID- 28503870
TI - Correcting hazard ratio estimates for outcome misclassification using multiple
imputation with internal validation data.
AB - OBJECTIVE: Outcome misclassification may occur in observational studies using
administrative databases. We evaluated a two-step multiple imputation approach
based on complementary internal validation data obtained from two subsamples of
study participants to reduce bias in hazard ratio (HR) estimates in Cox
regressions. METHODS: We illustrated this approach using data from a surveyed
sample of 6247 individuals in a study of statin-diabetes association in Quebec.
We corrected diabetes status and onset assessed from health administrative data
against self-reported diabetes and/or elevated fasting blood glucose (FBG)
assessed in subsamples. The association between statin use and new onset diabetes
was evaluated using administrative data and the corrected data. By simulation, we
assessed the performance of this method varying the true HR, sensitivity,
specificity, and the size of validation subsamples. RESULTS: The adjusted HR of
new onset diabetes among statin users versus non-users was 1.61 (95% confidence
interval: 1.09-2.38) using administrative data only, 1.49 (0.95-2.34) when
diabetes status and onset were corrected based on self-report and undiagnosed
diabetes (FBG >= 7 mmol/L), and 1.36 (0.92-2.01) when corrected for self-report
and undiagnosed diabetes/impaired FBG (>= 6 mmol/L). In simulations, the multiple
imputation approach yielded less biased HR estimates and appropriate coverage for
both non-differential and differential misclassification. Large variations in the
corrected HR estimates were observed using validation subsamples with low
participation proportion. The bias correction was sometimes outweighed by the
uncertainty introduced by the unknown time of event occurrence. CONCLUSION:
Multiple imputation is useful to correct for outcome misclassification in time-to
event analyses if complementary validation data are available from subsamples.
Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28503871
TI - Subcellular distribution of calcium during spermatogenesis of zebrafish, Danio
rerio.
AB - Calcium plays a variety of vital regulatory functions in many physiological and
biochemical events in the cell. The aim of this study was to describe the
ultrastructural distribution of calcium during different developmental stages of
spermatogenesis in a model organism, the zebrafish (Danio rerio), using a
combined oxalate-pyroantimonate technique. Samples were treated by potassium
oxalate and potassium pyroantimonate during two fixation stages and examined
using transmission electron microscopy to detect electron dense intracellular
calcium. The subcellular distribution of intracellular calcium was characterized
in spermatogonium, spermatocyte, spermatid, and spermatozoon stages. The area
which is covered by intracellular calcium in different stages was quantified and
compared using software. Isolated calcium deposits were mainly detectable in the
cytoplasm and the nucleus of the spermatogonium and spermatocyte. In the
spermatid, calcium was partially localized in the cytoplasm as isolated deposits.
However, most calcium was transformed from isolated deposits into an unbound pool
(free calcium) within the nucleus of the spermatid and the spermatozoon.
Interestingly, in the spermatozoon, calcium was mainly localized in a form of an
unbound pool which was detectable as an electron-dense mass within the nucleus.
Also, sporadic calcium deposits were scattered in the midpiece and flagellum. The
proportional area which was covered by intracellular calcium increased
significantly from early to late stages of spermatogenesis. The extent of the
area which was covered by intracellular calcium in the spermatozoon was the
highest compared to earlier stages. Calcium deposits were also observed in the
somatic cells (Sertoli, myoid, Leydig) of zebrafish testis. The notable changes
in the distribution of intracellular calcium of germ cells during different
developmental stages of zebrafish spermatogenesis suggest its different
homeostasis and physiological functions during the process of male gamete
development.
PMID- 28503872
TI - The effect of brief digital interventions on attitudes to intellectual
disability: Results from a pilot study.
AB - BACKGROUND: Evidence on the effects of contact and education based interventions
on attitudes is limited in the intellectual disability field. This study compared
the effects of brief interventions with different education, indirect and
imagined contact components on lay people's attitudes. MATERIALS AND METHODS: 401
adult participants were randomised to six digital brief interventions consisting
of different combinations of education, indirect and imagined contact. Their
attitudes, intergroup anxiety and social distance were assessed post-intervention
and at four to six-week follow-up. RESULTS: An intervention combining film-based
education about intellectual disability and indirect contact had small positive
effects on all three outcomes. Social distance was further reduced with the
addition of a positively toned imagined contact task. These effects were
maintained at follow-up. CONCLUSIONS: A brief film-based digital intervention can
have small positive effects on attitudes to people with intellectual
disabilities. These may be enhanced by adding positive imagined contact.
PMID- 28503873
TI - Successful large volume 'lymphocentesis' for refractory lymphoedema in lower and
upper limbs.
PMID- 28503874
TI - Disturbances in blood flow and 'medicine's greatest imitator'.
AB - First described in 1959, intravascular lymphoma (IVL) remains one of the most
clinically challenging diagnoses due to its diverse and non-specific clinical
manifestations and evasiveness in detection by standard investigations. Indeed,
IVL deserves the title of 'medicine's greatest imitator'. We highlight a case of
IVL where the diagnosis came too late in the clinical course, detected by random
skin biopsy. Clinicians should strongly consider this diagnosis in presentations
with persistent symptomatology despite appropriate interventions.
PMID- 28503875
TI - A rare vascular complication in a patient with essential thrombocythaemia:
spontaneous abdominal aortic dissection.
AB - A 27-year-old woman complained of waist and back pain. Abdominal computed
tomography angiography showed abdominal aortic dissection, the blood count
revealed a high platelet count of 1655 * 109 /L. Negative for JAK2V617F, CALR and
MPL mutations (i.e. triple-negative), the patient was diagnosed as essential
thrombocythaemia (ET) with abdominal aortic dissection and was treated with
cytoreduction and antiplatelet drugs. Cases of abdominal aortic dissection in ET
have not been previously reported. As such, we proposed a mechanism of abdominal
aortic dissection caused by endothelial dysfunction and further emphasised
appropriate management in ET with abdominal aortic dissection.
PMID- 28503876
TI - The Melbourne thunderstorm asthma event: can we avert another strike?
PMID- 28503877
TI - Follicular lymphoma in pregnancy presenting as multiple aneuploidy on non
invasive prenatal testing.
PMID- 28503878
TI - Complementary and alternative medicine: conventional solution to an
unconventional problem.
PMID- 28503879
TI - Impact of an antimicrobial stewardship intervention on appropriateness of
prescribing for community-acquired pneumonia in an Australian regional hospital.
AB - Community-acquired pneumonia (CAP) is the second commonest indication for
antibiotic use in Australian hospitals and is therefore a frequent target for
antimicrobial stewardship. A single-centre prospective study was conducted in a
regional referral hospital comparing management of adult patients with CAP before
and after an educational intervention. We demonstrated a reduction in duration of
therapy and reduced inappropriate use of ceftriaxone-based regimens for non
severe CAP.
PMID- 28503880
TI - Individualised medicine: why we need Bayesian dosing.
AB - Individualised drug dosing has been shown to improve patient outcomes and reduce
adverse drug events. One method of individualised medicine is the Bayesian
approach, which uses prior information about how the population responds to
therapy, to inform clinicians about how a specific individual is responding to
their current therapy. This information is then used to make changes to the dose.
Studies using a Bayesian approach to adjust drug dosing have shown that
clinicians are able to achieve a therapeutic range quicker than standard
practice. If concentration is related to a pharmacodynamic end-point, this means
that the drug will be more effective, and the side-effects will be minimised.
Unfortunately, the software options to assist with Bayesian dosing in Australia
are limited. The aims of this article are to demystify the concepts of Bayesian
dosing, set the context of the Bayesian approach using reference to other dosing
strategies and discuss its benefits over current dosing methods for a number of
drugs. The article is targeted to medical and pharmacy clinicians, and there is a
practical clinical case to demonstrate how this method could be used in everyday
clinical practice.
PMID- 28503881
TI - A case of de novo diagnosis anti-neutrophil cytoplasmic antibody-negative pauci
immune necrotising glomerulonephritis in pregnancy.
PMID- 28503882
TI - Editor's Note.
PMID- 28503883
TI - Deaths from liver cancer continue to rise in Australia: is elimination by 2030
possible?
PMID- 28503884
TI - Do professional medical colleges serve a function in the 21st century?
PMID- 28503885
TI - Thunderstorm asthma.
PMID- 28503886
TI - Life-threatening drug interactions: what the physician needs to know.
AB - Adverse drug-drug interactions are a significant cause of adverse events and
outcomes. Their incidence is rising, with more patients taking more drugs, and
newer, more precise but often more hazardous drugs becoming available. Despite
considerable information, including computerised alerts about potential adverse
drug-drug interactions, prescribers increasingly override alerts, possibly
symptomatic of the immense problem of evaluating the risk of an interaction in a
particular patient. Many reports emanate from small studies often of normal and
young volunteers, entirely different from the real world where, more often, older
patients with multiple health conditions are receiving many more than the two
drugs identified in the drug interaction report. Focusing on those drug-drug
interactions that are clinically relevant is necessary, and increasingly, tools
and reliable sources of this information are easily accessible.
PMID- 28503887
TI - Editor's Note.
PMID- 28503888
TI - Cryoglobulinaemic glomerulonephritis: artefacts associated with laboratory
diagnosis and need for renal biopsy.
AB - Cryoglobulinemia as a cause of renal impairment is uncommon but needs to be
considered in viral hepatitis and haematological malignancies. Often detection
and estimation of cryoglobulins are confounded by collection and processing
errors. This report highlights the need for stringent processing measures if the
clinical suspicion is high.
PMID- 28503889
TI - Lanthanide Metal-Organic Framework Microrods: Colored Optical Waveguides and
Chiral Polarized Emission.
AB - Lanthanide metal-organic frameworks (Ln-MOFs) have received much attention owing
to their structural tunability and widely photofunctional applications. However,
successful examples of Ln-MOFs with well-defined photonic performances at micro
/nanometer size are still quite limited. Herein, self-assemblies of 1,3,5
benzenetricarboxylic acid (BTC) and lanthanide ions afford isostructural
crystalline Ln-MOFs. Tb-BTC, Eu@Tb-BTC, and Eu-BTC have 1D microrod morphologies,
high photoluminescence (PL) quantum yields, and different emission colors (green,
orange, and red). Spatially PL resolved spectra confirm that Ln-MOF microrods
exhibit an optical waveguide effect with low waveguide loss coefficient
(0.012~0.033 dB MUm-1 ) during propagation. Furthermore, these microrods feature
both linear and chiral polarized photoemission with high anisotropy.
PMID- 28503890
TI - Comorbidity and quality of life in childhood cancer survivors treated with proton
beam therapy.
AB - BACKGROUND: The rate of childhood cancer survival has recently reached >80%.
Various adverse events among childhood cancer survivors (CCS) have been reported.
Proton beams are able to avoid unnecessary irradiation to normal/vital organs. We
conducted a quality of life (QOL) study for CCS who were treated with proton beam
therapy (PBT). METHODS: We included those patients treated with PBT to the brain,
head, or neck and who were <=15 years old at the University of Tsukuba Hospital
between 1983 and 2011. Clinical information was collected from medical records.
Questionnaires including the Pediatric Quality of Life Inventory (PedsQL) 4.0
Generic Core Scales (which assess health-related quality of life) were sent to
the families/patients. RESULTS: Sixty patients were included. Median age at
treatment was 6.2 years. The number of patients with status alive/dead/unknown
was 32/24/4. Median follow-up period was 63.0 months (range, 48-340 months) for
survivors. Questionnaires were sent to 25 families/patients and 19 were returned.
PedsQL was assessed for 17 patients. Eleven of 32 living patients had at least
one comorbidity grade 3/4. Average QOL score was above that for Japanese
schoolchildren and adolescents. There was no correlation with comorbidity, and
only longer time from treatment was correlated with a higher PedsQL score (P =
0.006). CONCLUSION: CCS who were treated with multimodal treatment using PBT had
a higher QOL score. Higher score was related to longer time since treatment,
regardless of comorbidity.
PMID- 28503891
TI - The use of intravesical gentamicin to treat recurrent urinary tract infections in
lower urinary tract dysfunction.
AB - AIMS: To assess the use of intravesical gentamicin to treat intractable recurrent
urinary tract infections in lower urinary tract dysfunction. METHODS: A two
center retrospective cohort study of 27 patients treated with intravesical
gentamicin was performed over a 2-year period. A treatment protocol was
developed, reviewed, and accepted by the clinical effectiveness committee of both
hospitals. Patients were taught to instill the gentamicin into the bladder on a
nightly basis. Inclusion criteria included failure to respond to standard
therapy, having six or more cultured confirmed UTIs over a 12-month period, or at
least one hospital admission with sepsis. Serum gentamicin levels were taken
after 7 days and the treatment was discontinued if the level was >1 mg/L.
Patients were counseled about the limited evidence base for this treatment.
RESULTS: Twenty-seven patients have been treated with intravesical gentamicin for
an average of 26 months. Seventeen were performing ISC, five had suprapubic
catheters, three were voiding, and two had ileal conduits at the time of
instituting treatment. All patients started on daily 80 mg gentamicin. Twenty two
patients had less frequently occurring infections after starting intravesical
gentamicin treatment. Six stopped the treatment and none had side effects as a
result of the instillations. CONCLUSIONS: This study has shown that in a small
group of adult patients who have multiple symptomatic UTIs refractory to
conventional treatment, intravesical gentamicin is effective in reducing the
frequency of infections. The treatment is well tolerated with no evidence of
systemic absorption.
PMID- 28503892
TI - The Ethics of Clinical Trials Research in Severe Mood Disorders.
AB - Mood disorders, including major depressive disorder (MDD) and bipolar disorder
(BD), are highly prevalent, frequently disabling, and sometimes deadly.
Additional research and more effective medications are desperately needed, but
clinical trials research in mood disorders is fraught with ethical issues.
Although many authors have discussed these issues, most do so from a theoretical
viewpoint. This manuscript uses available empirical data to inform a discussion
of the primary ethical issues raised in mood disorders research. These include
issues of consent and decision-making capacity, including patients' motivations
for participating in research. We also address drug withdrawals, placebo
controls, and the overall safety of research. Finally, we examine the extant
literature for studies discussing potential indirect benefits of clinical trials
research to participants. Taken together, the evidence suggests that clinical
trials research incorporating drug withdrawals and placebo controls can be
conducted safely and ethically, even in patients with severe or treatment
resistant mood disorders. In fact, given the dearth of effective treatment
options for this population, it is our opinion that a moral imperative exists to
extend the offer of research participation to severely ill or treatment-resistant
groups.
PMID- 28503894
TI - Direct Mechanism of the First Carbon-Carbon Bond Formation in the Methanol-to
Hydrocarbons Process.
AB - In the past two decades, the reaction mechanism of C-C bond formation from either
methanol or dimethyl ether (DME) in the methanol-to-hydrocarbons (MTH) process
has been a highly controversial issue. Described here is the first observation of
a surface methyleneoxy analogue, originating from the surface-activated DME, by
in situ solid-state NMR spectroscopy, a species crucial to the first C-C bond
formation in the MTH process. New insights into the first C-C bond formation were
provided, thus suggesting DME/methanol activation and direct C-C bond formation
by an interesting synergetic mechanism, involving C-H bond breakage and C-C bond
coupling during the initial methanol reaction within the chemical environment of
the zeolite catalyst.
PMID- 28503895
TI - Quantitative comparative analysis of the nasal chemosensory organs of anurans
during larval development and metamorphosis highlights the relative importance of
chemosensory subsystems in the group.
AB - The anuran peripheral olfactory system is composed of a number of subsystems,
represented by distinct neuroepithelia. These include the main olfactory
epithelium and vomeronasal organ (found in most tetrapods) and three specialized
epithelia of anurans: the buccal-exposed olfactory epithelium of larvae, and the
olfactory recess and middle chamber epithelium of postmetamorphic animals. To
better characterize the developmental changes in these subsystems across the life
cycle, morphometric changes of the nasal chemosensory organs during larval
development and metamorphosis were analyzed in three different anuran species
(Rhinella arenarum, Hypsiboas pulchellus, and Xenopus laevis). We calculated the
volume of the nasal chemosensory organs by measuring the neuroepithelial area
from serial histological sections at four different stages. In larvae, the
vomeronasal organ was relatively reduced in R. arenarum compared with the other
two species; the buccal-exposed olfactory epithelium was absent in X. laevis, and
best developed in H. pulchellus. In postmetamorphic animals, the olfactory
epithelium (air-sensitive organ) was relatively bigger in terrestrial species (R.
arenarum and H. pulchellus), whereas the vomeronasal and the middle chamber
epithelia (water-sensitive organs) was best developed in X. laevis. A small
olfactory recess (likely homologous with the middle chamber epithelium) was found
in R. arenarum juveniles, but not in H. pulchellus. These results support the
association of the vomeronasal and middle chamber epithelia with aquatic
olfaction, as seen by their enhanced development in the secondarily aquatic
juveniles of X. laevis. They also support a role for the larval buccal-exposed
olfactory epithelium in assessment of oral contents: it was absent in X. laevis,
an obligate suspension feeder, while present in the two grazing species. These
initial quantitative results give, for the first time, insight into the
functional importance of the peripheral olfactory subsystems across the anuran
life cycle.
PMID- 28503893
TI - A comparison of two sources of methionine supplemented at different levels on
heat shock protein 70 expression and oxidative stress product of Peking ducks
subjected to heat stress.
AB - The aim of this study was to examine the effects of different sources and levels
of methionine (Met) on Heat shock proteins HSP70 expression and protein
carbonylation in liver, HSP70 expression and malondialdehyde (MDA) concentration
in intestine under heat stress conditions during summer. A total of 720 (4 days
old) Peking ducks were placed 20 per pen into six replicates for each of the six
treatments with a 2 * 3 factorial arrangement, such that two sources of Met (DL
methionine [DLM] and DL-2-hydroxy-4-methylthiobutyrate [HMTBA] were supplemented
at three different levels (0.05%, 0.20%, or 0.35% on as-fed basis respectively).
The experiment was divided into a starter (day 4-16) and a grower (day 17-35)
period. Diet supplemented with 0.35% Met significantly up-regulated the HSP70
mRNA expression in duodenum, jejunum and ileum on day 16 and 35 as well as in
liver on day 35 (p < .05) of ducks. HMTBA-supplemented diets increased the HSP70
mRNA expression in duodenum, jejunum, ileum and liver on day 35 (p < .01). An
increased MDA concentration was detected in jejunum of birds in 0.35% DLM
supplemented treatment on day 16 (p < .05). And decreased protein carbonylation
concentration was found in DLM-supplemented treatment on day 16 (p < .01). The
birds fed with 0.35% Met supplemental diet displayed lower hepatic protein
carbonylation on day 16 (p < .05). In conclusion, supplementation of 0.35% Met in
the duck diet showed up-regulated HSP70 expression in small intestine and liver,
which may provide new perspective to the mechanism of Met function. At the same
time, DLM supplemented in diet may ameliorate oxidative status of liver, while
HMTBA supplementation may partially improve the intestinal oxidative status of
Peking ducks.
PMID- 28503896
TI - Antibacterial efficacy of poly(vinyl alcohol) composite nanofibers embedded with
silver-anchored silica nanoparticles.
AB - Silver has been widely used as an effective antibacterial agent especially for
treating burns and wounds. However, release of silver from materials often arouse
side effects due to toxicity of silver towards mammalian cells. Argyria and
argyrosis are well known problems of acute toxicity of silver towards human body.
Immobilization of silver is an effective approach to reduce silver release.
Herein, we present poly(vinyl alcohol) (PVA) composite nanofibers embedded with
silver-anchored silica nanoparticles (SSNs) as a novel antibacterial material.
Silver nanoparticles anchored on silica nanoparticles were prepared and
incorporated into PVA nanofibers to fabricate silver-silica embedded PVA
nanofibers (SSN-PVA) by electrospinning. Incorporation of SSNs into PVA was
confirmed by TEM and SEM results revealed regular nanofibers whose diameter
increased with successive addition of SSNs. The SSN-PVA nanofibers showed
significant antibacterial efficacy against both Gram-negative and Gram-positive
bacteria. Our research results demonstrated SSN-embedded polymeric nanofibers can
open up a promising prospect for the prevention of bacterial infection in diverse
biomedical fields including wound dressing. (c) 2017 Wiley Periodicals, Inc. J
Biomed Mater Res Part B: Appl Biomater, 106B: 1121-1128, 2018.
PMID- 28503897
TI - Aggregate Formation of Oligonucleotides that Assist Molecular Imaging for
Tracking of the Oxygen Status in Tumor Tissue.
AB - The use of DNA aggregates could be a promising strategy for the molecular imaging
of biological functions. Herein, phosphorescent oligodeoxynucleotides were
designed with the aim of visualizing oxygen fluctuation in tumor cells. DNA
ruthenium conjugates (DRCs) that consisted of oligodeoxynucleotides, a
phosphorescent ruthenium complex, a pyrene unit for high oxygen responsiveness,
and a nitroimidazole unit as a tumor-targeting unit were prepared. In general,
oligonucleotides have low cell permeability because of their own negative
charges; however, the DRC formed aggregates in aqueous solution due to the
hydrophobic pyrene and nitroimidazole groups, and smoothly penetrated the
cellular membrane to accumulate in tumor cells in a hypoxia-selective manner. The
oxygen-dependent phosphorescence of DRC in cells was also observed. In vivo
experiments revealed that aggregates of DRC accumulated in hypoxic tumor tissue
that was transplanted into the left leg of mice, and showed that oxygen
fluctuations in tumor tissue could be monitored by tracking of the
phosphorescence emission of DRC.
PMID- 28503898
TI - Evaluation of initial setup errors of two immobilization devices for lung
stereotactic body radiation therapy (SBRT).
AB - The aim of this study was to investigate the accuracy and efficacy of two
commonly used commercial immobilization systems for stereotactic body radiation
therapy (SBRT) in lung cancer. This retrospective study assessed the efficacy and
setup accuracy of two immobilization systems: the Elekta Body Frame (EBF) and the
Civco Body Pro-Lok (CBP) in 80 patients evenly divided for each system. A cone
beam CT (CBCT) was used before each treatment fraction for setup correction in
both devices. Analyzed shifts were applied for setup correction and CBCT was
repeated. If a large shift (>5 mm) occurred in any direction, an additional CBCT
was employed for verification after localization. The efficacy of patient setup
was analyzed for 105 sessions (48 with the EBF, 57 with the CBP). Result
indicates that the CBCT was repeated at the 1st treatment session in 22.5% and
47.5% of the EBF and CBP cases, respectively. The systematic errors {left-right
(LR), anterior-posterior (AP), cranio-caudal (CC), and 3D vector shift: (LR2 +
AP2 + CC2 )1/2 (mm)}, were {0.5 +/- 3.7, 2.3 +/- 2.5, 0.7 +/- 3.5, 7.1 +/- 3.1}
mm and {0.4 +/- 3.6, 0.7 +/- 4.0, 0.0 +/- 5.5, 9.2 +/- 4.2} mm, and the random
setup errors were {5.1, 3.0, 3.5, 3.9} mm and {4.6, 4.8, 5.4, 5.3} mm for the EBF
and the CBP, respectively. The 3D vector shift was significantly larger for the
CBP (P < 0.01). The setup time was slightly longer for the EBF (EBF: 15.1 min,
CBP: 13.7 min), but the difference was not statistically significant. It is
concluded that adequate accuracy in SBRT can be achieved with either system if
image guidance is used. However, patient comfort could dictate the use of CBP
system with slightly reduced accuracy.
PMID- 28503899
TI - Effects of maternal treatment with beta-hydroxy-beta-metylbutyrate and 2
oxoglutaric acid on femur development in offspring of minks of the standard dark
brown type.
AB - The aim of the study was to evaluate the effect of the diet, mother type and sex
of the offspring on the mechanical and geometric parameters of long bones as well
as bone tissue density in minks. Primiparous and multiparous dams were
supplemented with beta-hydroxy beta-methylbutyrate (a metabolite of leucine, at
the daily dosage of 0.02 g/kg of body weight) and/or 2-oxoglutaric acid (a
precursor of glutamine, at the daily dosage of 0.4 g/kg of body weight) during
gestation. The diet did not influence bone tissue density and the length of the
humerus. An increase in the length of the femur was noted in male offspring
delivered by multiparous dams. The diet resulted in an increase in the weight of
the humerus in males from multiparous dams and a decrease in offspring from
primiparous dams. Heavier femora were noted in male offspring delivered by both
types of dams. The maximum elastic strength of the humerus was higher in the
offspring delivered by multiparous than primiparous dams, irrespective of the
offspring sex. The diet resulted in reduction in the ultimate strength of the
femur in the male offspring delivered by primiparous dams. Only females born by
multiparous dams, irrespective of the diet, showed a significant increase in the
cross-sectional area of the humerus, while a significant decline was noted in
males delivered by multiparous dams and in all the offspring delivered by
primiparous dams. An increase in the cross-sectional area of the femur was noted
in the offspring delivered by multiparous dams, while reduction was observed in
the offspring delivered by primiparous dams. These results have shown for the
first time that the presence of beta-hydroxy-beta-methylbutyrate or 2-oxoglutaric
acid in the diet of pregnant primiparous or multiparous dams unambiguously
affects the geometry and mechanical properties of offspring's long bones.
PMID- 28503900
TI - Effects of in ovo feeding of L-arginine on the development of digestive organs,
intestinal function and post-hatch performance of broiler embryos and hatchlings.
AB - This study was to investigate the effects of in ovo feeding (IOF) L-arginine
(Arg) solution on the development of digestive organs, the duodenal mucosa of
broiler embryos and hatchlings, and the growth performance of chicks during the
first week post-hatch. A total of 720 fertilized eggs with similar weight were
randomly allocated to three groups, consisting of eight replicates of 30 eggs
each. Three treatments were arranged as non-injected control, diluent-injected
(0.75% NaCl solution) group and Arg solution-injected group containing 1% Arg,
dissolved in diluent. At 17.5 days of incubation, 0.6 ml of IOF solution was
injected into amniotic fluid of each egg of injected groups. Results showed IOF
of Arg solution increased (p < .05) the chick embryo weight at 19 days of
incubation; the body weight gain of post-hatch broilers during 1-7 days; the
weights of liver, pancreas, proventriculus and gizzard; the concentrations of
duodenal ghrelin, vasoactive intestinal peptide and glucagon-like peptide 2; and
the duodenum mucosal enzyme activities of alkaline phosphatase, maltase, sucrase
and inducible nitric oxide synthase of 7-day-old post-hatch broilers compared
with other groups. The IOF of Arg solution also increased (p < .05) the villus
height (VH) and the ratio of VH to crypt depth (CD) and decreased (p < .05) the
CD in duodenum of broiler embryos and post-hatch hatchlings, except for the CD at
19 days of incubation. In conclusion, IOF of 1% Arg solution into the amnion at
17.5 days of incubation could improve the development of digestive organs, the
duodenal morphology, the releasing of gastrointestinal hormones and mucosal
enzyme activities of broiler embryos and hatchlings and finally the growth
performance of chicks during the first week post-hatch. Therefore, IOF of
appropriate Arg solution could be an effective technology for regulating early
nutrition supply and subsequent growth development in poultry industry.
PMID- 28503901
TI - Thermoluminescence properties of Eu-doped and Eu/Dy-codoped Sr2 Al2 SiO7
phosphors.
AB - We report the thermoluminescence properties of Sr1.96 Al2 SiO7 :Eu0.04 and Sr1.92
Al2 SiO7 :Eu0.04 Dy0.04 phosphors. These phosphors were prepared by a high
temperature solid-state reaction method. The prepared phosphors were
characterized by X-ray diffraction. A 254 nm source was used for ultraviolet (UV)
irradiation and a 60 Co source was used for gamma-irradiation. The effect of
heating rate and UV-exposure were examined. The thermoluminescence temperature
shifts to higher values with increasing heating rate and thermoluminescence
intensity increases with increasing UV exposure time. The trapping parameters
such as activation energy (E), order of kinetics and frequency factor (s) were
calculated by peak shape method. The effect of gamma- and UV-irradiation on
thermoluminescence studies was also examined.
PMID- 28503902
TI - Electrochemical and biocompatibility examinations of high-pressure torsion
processed titanium and Ti-13Nb-13Zr alloy.
AB - The purpose of this study was to estimate the electrochemical behavior and
biocompatibility of ultrafine-grained (UFG) commercially pure titanium (CPTi) and
Ti-13Nb-13Zr (TNZ) alloy obtained by high-pressure torsion process.
Electrochemical behavior of materials in artificial saliva at 37 degrees C was
evaluated by potentiodynamic polarization tests and electrochemical impedance
spectroscopy (EIS), and the obtained results indicated that UFG TNZ alloy showed
corrosion current density (jcorr = 53 +/- 5 nA cm-2 ) which was 2 times lower
compared to coarse-grained (CG) TNZ alloy (jcorr = 110 +/- 12 nA cm-2 ) and
higher corrosion resistance, while UFG CPTi and CPTi showed approximately the
same corrosion rate (mean jcorr ~ 38-40 nA cm-2 ). Static immersion test in
artificial saliva, performed in this study, showed that the released ion
concentrations from UFG materials were more than 10 times lower than the
permitted concentration (the highest released Ti ion concentration from UFG CPTi
and UFG TNZ alloy was 1.12 and 1.28 ppb, respectively, while permitted
concentration was 15.5 ppb). The in vitro cytotoxicity tests, as the initial
phase of the biocompatibility evaluation, showed that the fraction of surviving
cells in all examined materials was much higher compared to the control sample
and hence demonstrated absence of cytotoxicity and an increase of fibroblast
cells adhesion on UFG materials surfaces. UFG CPTi and UFG TNZ alloy can be
considered as promising materials for applications in dentistry due to high
corrosion resistance and outstanding biocompatibility which were shown in this
study. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater,
106B: 1097-1107, 2018.
PMID- 28503903
TI - The 23rd Annual Prostate Cancer Foundation Scientific Retreat report.
AB - INTRODUCTION: The 23rd Annual Prostate Cancer Foundation (PCF) Scientific Retreat
was convened October 27-29, 2016, in Carlsbad, CA. METHODS: This event focuses on
the latest advances in basic, translational, and clinical prostate cancer
research with the greatest promise for advancing our understanding of prostate
cancer biology and improving patient outcomes and quality of life. RESULTS:
Themes highlighted at this year's meeting included: i) targeting DNA repair
deficiency in prostate cancer; ii) optimizing the use of Radium-223 and bone
targeting agents; iii) advances in cancer immunotherapeutic approaches; iv)
targeting developmental pathways in prostate cancer; v) advances in circulating
tumor DNA technology and applications; vi) precision survivorship; and vii) novel
treatments and treatment strategies in prostate cancer. DISCUSSION: This article
reviews the key advances discussed at the Retreat for the purpose of
disseminating this knowledge to accelerate the development of new treatments and
improved outcomes for men suffering with prostate cancer.
PMID- 28503905
TI - Widespread hybridization within mound-building wood ants in Southern Finland
results in cytonuclear mismatches and potential for sex-specific hybrid
breakdown.
AB - Hybridization and gene flow between diverging lineages are increasingly
recognized as common evolutionary processes, and their consequences can vary from
hybrid breakdown to adaptive introgression. We have previously found a population
of wood ant hybrids between Formica aquilonia and F. polyctena that shows
antagonistic effects of hybridization: females with introgressed alleles show
hybrid vigour, whereas males with the same alleles show hybrid breakdown. Here,
we investigate whether hybridization is a general phenomenon in this species pair
and analyse 647 worker samples from 16 localities in Finland using microsatellite
markers and a 1200-bp mitochondrial sequence. Our results show that 27 sampled
nests contained parental-like gene pools (six putative F. polyctena and 21
putative F. aquilonia) and all remaining nests (69), from nine localities,
contained hybrids of varying degrees. Patterns of genetic variation suggest these
hybrids arise from several hybridization events or, instead, have backcrossed to
the parental gene pools to varying extents. In contrast to expectations, the
mitochondrial haplotypes of the parental species were not randomly distributed
among the hybrids. Instead, nests that were closer to parental-like F. aquilonia
for nuclear markers preferentially had F. polyctena's mitochondria and vice
versa. This systematic pattern suggests there may be underlying selection
favouring cytonuclear mismatch and hybridization. We also found a new hybrid
locality with strong genetic differences between the sexes similar to those
predicted under antagonistic selection on male and female hybrids. Further
studies are needed to determine the selective forces that act on male and female
genomes in these newly discovered hybrids.
PMID- 28503906
TI - More Than Words: The Role of Multiword Sequences in Language Learning and Use.
AB - The ability to convey our thoughts using an infinite number of linguistic
expressions is one of the hallmarks of human language. Understanding the nature
of the psychological mechanisms and representations that give rise to this unique
productivity is a fundamental goal for the cognitive sciences. A long-standing
hypothesis is that single words and rules form the basic building blocks of
linguistic productivity, with multiword sequences being treated as units only in
peripheral cases such as idioms. The new millennium, however, has seen a shift
toward construing multiword linguistic units not as linguistic rarities, but as
important building blocks for language acquisition and processing. This shift
which originated within theoretical approaches that emphasize language learning
and use-has far-reaching implications for theories of language representation,
processing, and acquisition. Incorporating multiword units as integral building
blocks blurs the distinction between grammar and lexicon; calls for models of
production and comprehension that can accommodate and give rise to the effect of
multiword information on processing; and highlights the importance of such units
to learning. In this special topic, we bring together cutting-edge work on
multiword sequences in theoretical linguistics, first-language acquisition,
psycholinguistics, computational modeling, and second-language learning to
present a comprehensive overview of the prominence and importance of such units
in language, their possible role in explaining differences between first- and
second-language learning, and the challenges the combined findings pose for
theories of language.
PMID- 28503907
TI - Proteomics analysis for asymmetric inheritance of preexisting proteins between
mother and daughter cells in budding yeast.
AB - In budding yeast, a mother cell can produce a finite number of daughter cells
over its life. The accumulation of a variety of types of damaged components has
an impact on the aging process. Asymmetrical inheritance during cell division
causes these aberrant intracellular constituents to be retained in mother cells
and prevents them from segregating to daughter cells. However, the understanding
of asymmetrical inheritance of individual proteins that are damaged or old age,
and their relevance to the aging process, has been limited. The aim of this study
is to propose a proteomics strategy for asymmetrical inheritance of preexisting
proteins between mother and daughter cells. During synchronous culture for one
generation, newly synthesized proteins were labeled with stable isotope amino
acids to discriminate preexisting proteins originally expressed in mother cells,
followed by separation of mother and daughter cells using a conventional method
based on biotin labeling. Isotope incorporation ratios for individual proteins
were quantified using mass spectrometry. We successfully identified 21 proteins
whose preexisting versions were asymmetrically inherited in mother cells,
including plasma membrane transporter involved in the aging process and organelle
anchoring proteins related to the stress response to misfolded proteins. Thus,
our approach would be useful for making catalog of asymmetrically inherited
proteins.
PMID- 28503908
TI - Microheterogeneity in imidazolium and piperidinium cation-based ionic liquids: 1D
and 2D NMR studies.
AB - Existence of microheterogeneity of imidazolium and piperidinium cation-based
ionic liquids (ILs) containing PF6 and NTf2 anions has been investigated by 1D
and 2D NMR spectroscopy. 2D NMR (especially NOESY and HOESY) has been employed
for studying the interactions present between cation and anion as well as the
intermolecular interaction among cations. HOESY spectrum shows that fluorine of
anion ( PF6- and NTf2-) significantly interacts with proton of the cations.
Combined results of HOESY and NOESY for imidazolium IL indicate that the PF6- and
imidazolium cation are distributed in organized manner, resulting a heterogeneous
environment in liquid state. We have also observed existence of heterogeneous
environment for piperidinium cation-based ILs which is different from imidazolium
ILs. It appears that existence of microheterogeneity in IL is ubiquitous and
therefore open up the ILs field to revisit. Copyright (c) 2017 John Wiley & Sons,
Ltd.
PMID- 28503904
TI - White matter compromise in autism? Differentiating motion confounds from true
differences in diffusion tensor imaging.
AB - Common findings from diffusion tensor imaging (DTI) in autism spectrum disorder
(ASD) include reduced fractional anisotropy (FA), and increased mean and radial
diffusivity (MD, RD) of white matter tracts. However, findings may be confounded
by head motion. We examined how group-level motion matching affects DTI
comparisons between ASD and typically developing (TD) groups. We included 57 ASD
and 50 TD participants, comparing three subsets at increasing levels of motion
matching stringency: full sample (FS); quality-controlled (QC); and
quantitatively-matched (QM). Groups were compared on diffusivity measures using
Tract-Based Spatial Statistics (TBSS) and probabilistic tractography. Two methods
for estimating diffusivity were compared: dti-fit and restore. TBSS: In set FS,
FA was reduced in the ASD compared to the TD group throughout the right
hemisphere. This effect was less extensive in set QC and absent in set QM.
However, effect sizes remained stable or increased with better quality-control in
some regions. Tractography: In set QM, MD was significantly higher in ASD overall
and RD was higher in bilateral ILF. Effects were more robust in QM than in FS or
QC sets. Effect sizes in several tracts increased with stringent quality
matching. Restore improved tensor estimates, with some increases in effect sizes,
but did not fully compensate for reduced quality. Findings suggest that some
previously reported DTI findings for ASD may have been confounded by motion.
However, effects in the tightly matched subset indicate that tract-specific
anomalies probably do exist in ASD. Our results highlight the need for careful
quality-control and motion-matching. Autism Res 2017, 10: 1606-1620. (c) 2017
International Society for Autism Research, Wiley Periodicals, Inc.
PMID- 28503909
TI - Genetic risk score and cardiovascular mortality in a southern european population
with coronary artery disease.
AB - : Several genetic risk scores (GRS) have been associated with cardiovascular
disease; their role, however, in survival from proven coronary artery disease
(CAD) have yielded conflicting results. OBJECTIVE: The objective of this study
was to evaluate long-term cardiovascular mortality according to the genetic risk
score in a Southern European population with CAD. METHODS: A cohort of 1464 CAD
patients with angiographic proven CAD were followed up prospectively for up to
58.3 (interquartile range: 25.8-88.1) months. Genotyping of 32 single-nucleotide
polymorphisms previously associated with CAD was performed using oligonucleotides
probes marked with fluorescence for each allele. GRS was constructed according to
the additive model assuming codominance and categorised using the median (=26).
Cox Regression analysis was performed to determine independent multivariate
predictors of cardiovascular mortality. Kaplan-Meier survival curves compared
high vs low GRS using log-rank test. C-index was done for our population, as a
measure of discrimination in survival analysis model. RESULTS: During a mean
follow-up of 58.3 months, 156 patients (10.7%) died, 107 (7.3%) of CV causes.
High GRS (>=26) was associated with reduced cardiovascular survival. Survival
analysis with Cox regression model adjusted for 8 variables showed that high GRS,
dyslipidemia, diabetes and 3-vessel disease were independent risk factors for
cardiovascular mortality (HR=1.53, P=.037; HR=3.64, P=.012; HR=1.75, P=.004;
HR=2.97, P<.0001, respectively). At the end of follow-up, the estimated survival
probability was 70.8% for high GRS and 80.8% for low GRS (Log-rank test 5.6;
P=.018). C-Index of 0.71 was found when GRS was added to a multivariate survival
model of diabetes, dyslipidemia, smoking, hypertension and 3 vessel disease,
stable angina and dual antiplatelet therapy. CONCLUSIONS: Besides the classical
risk factors management, this work highlights the relevance of the genetic
profile in survival from CAD. It is expected that new therapies will be dirsected
to gene targets with proven value in cardiovascular survival.
PMID- 28503911
TI - Community football teams for people with intellectual disabilities in secure
settings: "They take you off the ward, it was like a nice day, and then you get
like medals at the end".
AB - BACKGROUND: People with learning disabilities (LD) are particularly vulnerable to
mental health and behavioural difficulties, and it has been shown that regular
exercise can improve psychosocial well-being as well as physical fitness. This
research aims to explore the experiences of men with LD detained in secure
settings who have engaged in community football training programmes and identify
the benefits of such provision. METHOD: Interviews were conducted with eight
patients in a forensic LD service, discussing their experiences of participating
in community football. Template analysis was undertaken on the transcripts.
RESULTS: Two master themes were identified: physical fitness and psychosocial
benefits. As the analysis progressed, new emerging themes were identified around
role identity and achievement, as well as extending and refining some of the
themes from the original template including fun and belonging. Some anticipated
themes were removed from the template entirely. CONCLUSION: The psychosocial
benefits of organised community sports programmes far outweigh the physical
health benefits. Careful consideration must be given to where on a treatment and
rehabilitation pathway non-traditional therapeutic interventions such as sports
programmes are offered as an adjunct to specific risk reduction interventions for
people with LD in secure settings.
PMID- 28503913
TI - Dual-fluorophore Raspberry-like Nanohybrids for Ratiometric pH Sensing.
AB - We report on the development of raspberry-like silica structures formed by the
adsorption of 8-hydroxypyrene-1,3,6-trisulfonate (HPTS)@silica nanoparticles
(NPs) on rhodamine B isothiocyanate (RBTIC)@silica NPs for ratiometric
fluorescence-based pH sensing. To overcome the well-known problem of dye leaching
which occurs during encapsulation of anionic HPTS dye in silica NPs, we utilized
a polyelectrolyte-assisted incorporation of the anionic HPTS. The morphological
and optical characterization of the as-synthesized dye-doped NPs and the
resulting nanohybrids were carried out. The pH-sensitive dye, HPTS, incorporated
in the HPTS-doped silica NPs provided a pH-dependent fluorescence response while
the RBITC-doped silica provided the reference signal for ratiometric sensing. We
evaluated the effectiveness of the nanohybrids for pH sensing; the ratio of the
fluorescence emission intensity at 510 nm and 583 nm at excitation wavelengths of
454 nm and 555 nm, respectively. The results showed a dynamic response in the
acidic pH range. With this approach, nanohybrids containing different dyes or
receptors could be developed for multifunctioning and multiplexing applications.
PMID- 28503910
TI - Postzygotic single-nucleotide mosaicisms contribute to the etiology of autism
spectrum disorder and autistic traits and the origin of mutations.
AB - The roles and characteristics of postzygotic single-nucleotide mosaicisms (pSNMs)
in autism spectrum disorders (ASDs) remain unclear. In this study of the whole
exomes of 2,361 families in the Simons Simplex Collection, we identified 1,248
putative pSNMs in children and 285 de novo SNPs in children with detectable
parental mosaicism. Ultra-deep amplicon resequencing suggested a validation rate
of 51%. Analyses of validated pSNMs revealed that missense/loss-of-function (LoF)
pSNMs with a high mutant allele fraction (MAF>= 0.2) contributed to ASD diagnoses
(P = 0.022, odds ratio [OR] = 5.25), whereas missense/LoF pSNMs with a low MAF
(MAF<0.2) contributed to autistic traits in male non-ASD siblings (P = 0.033).
LoF pSNMs in parents were less likely to be transmitted to offspring than neutral
pSNMs (P = 0.037), and missense/LoF pSNMs in parents with a low MAF were
transmitted more to probands than to siblings (P = 0.016, OR = 1.45). We
estimated that pSNMs in probands or de novo mutations inherited from parental
pSNMs increased the risk of ASD by approximately 6%. Adding pSNMs into the
transmission and de novo association test model revealed 13 new ASD risk genes.
These results expand the existing repertoire of genes involved in ASD and shed
new light on the contribution of genomic mosaicisms to ASD diagnoses and autistic
traits.
PMID- 28503914
TI - A Pd@Zeolite Catalyst for Nitroarene Hydrogenation with High Product Selectivity
by Sterically Controlled Adsorption in the Zeolite Micropores.
AB - The adsorption of molecules on metal nanoparticles can be sterically controlled
through the use of zeolite crystals, which enhances the product selectivity in
hydrogenations of reactants with more than one reducible group. Key to this
success was the fixation of Pd nanoparticles inside Beta zeolite crystals to form
a defined structure (Pd@Beta). In the hydrogenation of substituted nitroarenes
with multiple reducible groups as a model reaction, the Pd@Beta catalyst
exhibited superior selectivity for hydrogenation of the nitro group,
outperforming both conventional Pd nanoparticles supported on zeolite crystals
and a commercial Pd/C catalyst. The extraordinary selectivity of Pd@Beta was
attributed to the sterically selective adsorption of the nitroarenes on the Pd
nanoparticles controlled by the zeolite micropores, as elucidated by competitive
adsorption and adsorbate displacement tests. Importantly, this strategy is
general and was extended to the synthesis of selective Pt and Ru catalysts by
fixation inside Beta and mordenite zeolites.
PMID- 28503912
TI - High burden of metabolic comorbidities in a citywide cohort of HIV outpatients:
evolving health care needs of people aging with HIV in Washington, DC.
AB - OBJECTIVES: With the increasing impact of cardiovascular disease among
populations aging with HIV, contemporary prevalence estimates for predisposing
metabolic comorbidities will be important for guiding the provision of relevant
lifestyle and pharmacological interventions. We estimated the citywide prevalence
of hypertension, type 2 diabetes, dyslipidaemia, and obesity; examined
differences by demographic subgroups; and assessed clinical correlates. METHODS:
Utilizing an electronic medical record (EMR) database from the DC Cohort study -
a multicentre prospective cohort study of HIV-infected outpatients - we assessed
the period prevalence of metabolic comorbidities between 2011 and 2015 using
composite definitions that incorporated diagnoses, pharmacy records, and
clinical/laboratory results. RESULTS: Of 7018 adult patients (median age 50
years; 77% black), 50% [95% confidence interval (CI) 49-51] had hypertension, 13%
(95% CI: 12-14) had diabetes, 48% (95% CI: 47-49) had dyslipidaemia, and 35% (95%
CI: 34-36) had obesity. Hypertension was more prevalent among black patients,
diabetes and obesity were more prevalent among female and black patients,
dyslipidaemia was more prevalent among male and white patients, and comorbidities
were more prevalent among older patients (all P < 0.001). For many patients,
evidence of treatment for these comorbidities was not available in the EMR.
Longer time since HIV diagnosis, greater duration of antiretroviral treatment,
and having controlled immunovirological parameters were associated with metabolic
comorbidities. CONCLUSIONS: These findings underscore the pervasive burden of
metabolic comorbidities among HIV-infected persons, serve as the basis for future
analyses characterizing their impact on subsequent adverse cardiovascular
outcomes, and highlight the need for an increased focus on the prevention and
control of comorbid complications in this population.
PMID- 28503915
TI - Dual therapy with a combination of unboosted atazanavir and lamivudine as
maintenance treatment in virologically suppressed HIV-1-infected patients.
PMID- 28503916
TI - Exploratory study of the association of volumetric modulated arc therapy (VMAT)
plan robustness with local failure in head and neck cancer.
AB - This work is to show which is more relevant to cause local failures (LFs) due to
patient setup uncertainty between the planning target volume (PTV) underdosage
and the potential target underdosage subject to patient setup uncertainties in
head and neck (H&N) cancer treated with volumetric-modulated arc therapy (VMAT).
Thirteen LFs in 10 H&N patients treated by VMAT were analyzed. Measures have been
taken to minimize the chances of insufficient target delineation for these
patients and the patients were clinically determined to have LF based on the
PET/CT scan results by an experienced radiologist and then reviewed by a second
experienced radiation oncologist. Two methods were used to identify the possible
locations of LF due to underdosage: (a) examining the standard VMAT plan, in
which the underdosed volume in the nominal dose distribution (UVN) was generated
by subtracting the volumes receiving the prescription doses from PTVs, and (b)
plan robustness analysis, in which in addition to the nominal dose distribution,
six perturbed dose distributions were created by translating the CT iso-center in
three cardinal directions by the PTV margin. The coldest dose distribution was
represented by the minimum of the seven doses in each voxel. The underdosed
volume in the coldest dose distribution (UVC) was generated by subtracting the
volumes receiving the prescription doses in the coldest dose distribution from
the volumes receiving the prescription doses in the nominal dose distribution.
UVN and UVC were subsequently examined for spatial association with the locations
of LF. The association was tested using the binominal distribution and the
Fisher's exact test of independence. We found that of 13 LFs, 11 were associated
with UVCs (P = 0.011), while three were associated with UVNs (P = 0.99). We
concluded that the possible target underdosage due to patient setup uncertainties
appeared to be a more relevant factor associated with LF in VMAT for H&N cancer
than the compromised PTV coverage at least for the patients included in this
study.
PMID- 28503917
TI - A Smart Flexible Zinc Battery with Cooling Recovery Ability.
AB - Flexible batteries are essential for wearable electronic devices. To meet
practical applications, they need to be mechanically robust and stable. However,
strong or multiple bending may sever the interfacial contact between electrode
and electrolyte, causing capacity fading or even battery failure. Herein we
present a new cooling-recovery concept for flexible batteries, which involves a
temperature-sensitive sol-gel transition behavior of the thermoreversible polymer
hydrogel electrolyte. Once a battery has suffered from strong mechanical
stresses, a simple cooling process can refresh the electrode-electrolyte
interface. The energy-storage capability can be recovered with a healing
efficiency higher than 98 %. It is believed that this study not only offers new
valuable insights, but also opens up new perspectives to develop functional
wearable devices.
PMID- 28503919
TI - Gold Nanoparticle Based Hairpin-Locked-DNAzyme Probe for Amplified miRNA Imaging
in Living Cells.
AB - A new class of intracellular nanoprobe, termed AuNP-based hairpin-locked-DNAzyme
probe, was developed to sense miRNA in living cells. Briefly, it consists of an
AuNP and hairpin-locked-DNAzyme strands. In the absence of target miRNA, the
hairpin-locked-DNAzyme strand forms a hairpin structure by intramolecular
hybridization, which could inhibit the catalytic activity of DNAzyme strand and
the fluorescence is quenched by the AuNP. However, in the presence of target, the
target-probe hybridization can open the hairpin and form the active secondary
structure in the catalytic cores to yield an "active" DNAzyme, which then cleaves
the self-strand with the assist of Mg2+. The cleaved two shorter DNA fragments
are separated with the target. As a result, the fluorophores are released from
the AuNP and the fluorescence is enhanced. Meanwhile, the target is also released
and binds to another hairpin-locked-DNAzyme strand to drive another cycle of
activation. In such a way, the target-recycling amplification leads to
significant signal enhancement and thus offers high detection sensitivity.
PMID- 28503920
TI - Quantification of the Depolarization and Anisotropy of Fluorophore Stokes-Shifted
Fluorescence, On-Resonance Fluorescence, and Rayleigh Scattering.
AB - Fluorophores are important but optically complicated photonic materials as they
are simultaneous photon absorbers, emitters, and scatterers. Existing studies on
fluorophore optical properties have been focused almost exclusively on its photon
absorption and Stokes-shifted fluorescence (SSF) with scant information on the
fluorophore photon scattering and on-resonance fluorescence (ORF). Presented
herein is a unified theoretical framework and experimental approach for
quantification of the fluorophore SSF, ORF, and scattering depolarization and
anisotropy using a combination of fluorophore UV-vis, fluorescence emission, and
resonance synchronous spectroscopic spectral measurements. A mathematical model
for calculating fluorophore ORF and scattering cross sections has been developed
that uses polystyrene nanoparticles as the external reference. The fluorophore
scattering cross section is ~10-fold smaller than its ORF counterparts for all
the six model fluorophores, but more than 6 orders of magnitude larger than the
water scattering cross section. Another finding is that the fluorophore ORF has a
depolarization close to 1, while its Rayleigh scattering has zero depolarization.
This enables the experimental separation of the fluorophore ORF and photon
scattering features in the fluorophore resonance synchronous spectra. In addition
to opening a new avenue for material characterization, the methods and insights
derived from this study should be important for developing new analytical methods
that exploit the fluorophore ORF and photon scattering properties.
PMID- 28503918
TI - Design, Synthesis, and Structure-Activity Relationship Analysis of Thiazolo[3,2
a]pyrimidine Derivatives with Anti-inflammatory Activity in Acute Lung Injury.
AB - Acute lung injury (ALI) has a high lethality rate, and interleukin-6 (IL-6) and
tumor necrosis factor-alpha (TNF-alpha) contribute most to tissue deterioration
in cases of ALI. In this study, we designed and synthesized a new series of
thiazolo[3,2-a]pyrimidine derivatives based on a previously identified lead
compound, and we evaluated their anti-inflammatory activities. Structure-activity
relationship studies led to the discovery of two highly potent inhibitors. The
two promising compounds were found to inhibit lipopolysaccharide (LPS)-induced IL
6 and TNF-alpha release in a dose-dependent manner in mouse primary peritoneal
macrophages (MPMs). Furthermore, administration of these compounds resulted in
lung histopathological improvements and attenuated LPS-induced ALI in vivo. Taken
together, these data indicate that these novel thiazolo[3,2-a]pyrimidine
derivatives could be developed as candidate drugs for the treatment of ALI.
PMID- 28503921
TI - Fluorescent Nanoparticles with Tissue-Dependent Affinity for Live Zebrafish
Imaging.
AB - Carbon quantum dots (CDs) are widely investigated because of their low toxicity,
outstanding water solubility, and high biocompatibility. Specifically,
fluorescent CDs have attracted ever-increasing interest. However, so far, only a
few studies have focused on assessing the fluorescence of nitrogen-doped CDs
(N@CDs) during in vivo exposure. Here, we describe a strategy for low-cost, one
pot synthesis of N@CDs. The low toxicity and suitability of the N@CDs for
fluorescence imaging are validated using zebrafish (ZF) as a model. Strong
fluorescence emission from ZF embryos and larvae confirms the distribution of
N@CDs in ZF. The retention of N@CDs is very stable, long lasting, and with no
detectable toxicity. The presence of a strong fluorescence at the yolk sac,
especially in the vicinity of the intestine, suggests that a high content of
N@CDs entered the digestive system. This indicates that N@CDs may have potential
imaging applications in elucidating different aspects of lipoprotein and
nutritional biology, in a ZF yolk lipid transport and metabolism model. On the
other hand, the presence of a strong selective fluorescence at the eyes and
melanophore strips at the trunk and tail region of ZF larvae suggests that N@CDs
has a high melanin-binding affinity. These observations support a novel and
revolutionary use of N@CDs as highly specific bioagents for eye and skin imaging
and diagnosis of defects in them. N@CDs are known for their multifunctional
applications as highly specific bioagents for various biomedical applications
because of their exceptional biocompatibility, photostability, and selective
affinity. These characteristics were validated in the developmental ZF model.
PMID- 28503922
TI - Solution-Processed Highly Superparamagnetic and Conductive PEDOT:PSS/Fe3O4
Nanocomposite Films with High Transparency and High Mechanical Flexibility.
AB - Multifunctional films can have important applications. Transparent and flexible
films with high conductivity and magnetic properties can be used in many areas,
such as electromagnetic interference (EMI) shielding, magnetic switching,
microwave absorption, and also biotechnology. Herein, novel highly conductive and
superparamagnetic thin films with excellent transparency and flexibility have
been demonstrated. The films were formed from a poly(3,4
ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS; Clevios PH1000)
aqueous solution added with iron oxide (Fe3O4) nanoparticles that have a size of
~20 nm by spin-coating. The PEDOT:PSS/Fe3O4 films have a high conductivity of
1080 S/cm through treatment with methylammonium iodide in an organic solvent. The
high-conductivity PEDOT:PSS/Fe3O4 films can also have a saturation magnetization
of 25.5 emu/g and an EMI shielding effectiveness of more than 40 dB in the 8-12.5
GHz (X band) frequency range. The PEDOT:PSS/Fe3O4 films have additional
advantages, like excellent transparency, good mechanical flexibility, low cost,
and light weight. In addition, we fabricate flexible PEDOT:PSS/Fe3O4 silk threads
with a high magnetism and conductivity.
PMID- 28503923
TI - Sterically Shielded Electron Transporting Material with Nearly 100% Internal
Quantum Efficiency and Long Lifetime for Thermally Activated Delayed Fluorescent
and Phosphorescent OLEDs.
AB - A high triplet energy (T1) is usually taken as the prerequisite of the good
exciton confinement of electron transporting materials (ETMs); however, there is
usually a tradeoff with large mobility and stability. Here, we demonstrated that
good exciton confinement can also be realized utilizing a low-T1 ETM with a
sterically shielding low-T1 unit. Given the short-range interaction of the Dexter
energy transfer, the large steric side groups of the low-T1 ETM can effectively
hinder the T1 of the emitters from being quenched by increasing the
intermolecular distance. Based on this concept, a maximum external quantum
efficiency (EQEmax) as high as 21.3% was observed in the sky-blue thermally
activated delayed fluorescence device using a low-T1 ETM, with the EQE remaining
at 21.2% at 1000 cd/m2 and 17.8% at 5000 cd/m2. Further, an EQEmax as high as
25.5%, a low turn-on voltage of 2.3 V, as well as a long T90 of over 400 h at an
initial luminance of 5000 cd/m2 were achieved for green phosphorescent devices.
This work highlights a viable strategy for developing high-performance ETMs,
paving their way toward practical applications.
PMID- 28503924
TI - Complete Prevention of Dendrite Formation in Zn Metal Anodes by Means of Pulsed
Charging Protocols.
AB - Zn metal as anode in rechargeable batteries, such as Zn/air or Zn/Ni, suffers
from poor cyclability. The formation of Zn dendrites upon cycling is the key
limiting step. We report a systematic study of the influence of pulsed
electroplating protocols on the formation of Zn dendrites and in turn on
strategies to completely prevent Zn dendrite formation. Because of the large
number of variables in electroplating protocols, a scanning droplet cell
technique was adapted as a high-throughput methodology in which a descriptor of
the surface roughness can be in situ derived by means of electrochemical
impedance spectroscopy. Upon optimizing the electroplating protocol by
controlling nucleation, zincate ion depletion, and zincate ion diffusion,
scanning electron microscopy and atomic force microscopy confirmed the growth of
uniform and homogenous Zn deposits with a complete prevention of dendrite growth.
The implementation of pulsed electroplating as the charging protocol for
commercially available Ni-Zn batteries leads to substantially prolonged
cyclability demonstrating the benefits of pulsed charging in Zn metal-based
batteries.
PMID- 28503925
TI - Proteomics Provides Insight into the Interaction between Mulberry and Silkworm.
AB - Mulberry leaves have been selected as a food source for the silkworm (Bombyx
mori) for over 5000 years. However, the interaction mechanisms of mulberry
silkworm remain largely unknown. We explore the interaction between mulberry and
silkworm at the protein level. Total proteins were extracted from mulberry leaves
and silkworm feces on day 5 of the fifth larval instar and analyzed on shotgun
liquid chromatography-tandem mass spectrometry, respectively. In total, 2076 and
210 foliar proteins were identified from mulberry leaves and silkworm feces,
respectively. These proteins were classified into four categories according to
their subcellular location: chloroplast proteins, mitochondrial proteins,
secretory-pathway proteins, and proteins of other locations. Chloroplast proteins
accounted for 68.3% in mulberry leaves but only 23.2% in the feces. In contrast,
secretory-pathway proteins had low abundance in mulberry leaves (7.3%) but were
greatly enriched to the largest component in the feces (60.1%). Most of the
foliar secretory-pathway proteins in the feces were found to be resistant to
silkworm feeding by becoming involved in primary metabolite, proteinase
inhibition, cell-wall remodeling, redox regulation, and pathogen-resistant
processes. On the contrary, only six defensive proteins were identified in the
fecal chloroplast proteins including two key proteins responsible for
synthesizing jasmonic acid, although chloroplast proteins were the second largest
component in the feces. Collectively, the comparative proteomics analyses
indicate that mulberry leaves not only provide amino acids to the silkworm but
also display defense against silkworm feeding, although the silkworm grows very
well by feeding on mulberry leaves, which provides new insights into the
interactions between host-plant and insect herbivores.
PMID- 28503927
TI - Infectious complications in chronic lymphocytic leukemia- a retrospective
analysis: single institution experience.
AB - The aim of this study was to evaluate the incidence of a variety of infectious
complications in patients with CLL regarding the duration of CLL and the type of
treatment. We present the retrospective analysis of patients with CLL treated at
our institution in years 2004-2016. We collected data about the type of
infection, pathogenes, treatment and severity of infections surpassed in
connection with administration treatment. In the study one hundred and ten
patients were evaluated. The average age of patients was 61.7 years (range 34.5
91.9 years). Fludarabine was the most widely used regimen, followed by
bendamustine and alemtuzumab. We recorded 393 episodes of infections, of which
114 (29%) were severe and life threatening of degree 3-5, and 279 (71%) of degree
2. The most common infections were the upper respiratory tract infections
together with sinusitis (45.03%), pneumonia (26.20%), CMV reactivation occured in
8.14%, infections of the skin was in 7.6 %. Most infections have occurred with
the administration of monoclonal antibody alemtuzumab, these patients were at
significantly higher risk of infection [RR 2.59 (1.30 to 5.17)] than patients
receiving obinutuzumab [RR 0.63 (0.48 to 0.82)] (p = 0.0001). On the contrary,
the safety profile of BCR signaling pathway inhibitors was very acceptable [RR
1.17 (0.70 - 1.96)]. The number of infections have decreased during the first 12
months of treatment with ibrutinib. In the study group we recorded 19 deaths, 8
(7.27%) of them were of infectious etiology. The risk of infectious complications
is lifelong in patients with CLL, it can be minimized by early detection and
aggressive management. Novel targeted agents used in therapy of CLL have a good
safety profile, even the risk of infection is decreased during administration.
PMID- 28503928
TI - Effect of intermittent feeding and oat hulls to improve phytase efficacy and
digestive function in broiler chickens.
AB - 1. Two trials were carried out to investigate the impact of intermittent feeding
and oat hulls as methods to stimulate the anterior digestive tract in broiler
chickens. 2. In Trial 1, 7-d-old broilers were placed 4 per cage in 48 cages and
fed either ad libitum or intermittently on a diet with 50 g/kg of either oat
hulls or cellulose, with or without 1000 FTU phytase, in a 2 * 2 * 2 factorial
arrangement. Ad libitum fed birds had two 4-h dark periods with 1-h light in
between, while intermittently fed birds in addition had restricted access to feed
through four 1 h feeding bouts. 3. In Trial 2, 144 broiler chickens were divided
amongst 12 pens which were intermittently fed on the same diets as in Trial 1 in
a 2 * 2 factorial arrangement. At 34 d of age, after 16 h feed withdrawal, birds
were fed for 1 h, followed by dissection of 4 birds per treatment every hour for
9 h. Contents from different segments of the digestive tract were collected
quantitatively to assess dry matter (DM) and starch flow. 4. In Trial 1, phytase
improved performance and nutrient availability, while oat hulls and intermittent
feeding improved some measures of nutrient availability. Intermittent feeding
augmented the effect of phytase on myo-inositol hexakisphosphate (IP6)
degradation in the anterior digestive tract. 5. In Trial 2, birds filled up their
crop and slowly passed these contents on to lower segments of the digestive
tract. Already 1 h after commencement of feeding, the entire length of the small
intestine was filled with DM, and no significant changes in DM content were
observed before 4-5 h later, when the small intestine gradually became emptied.
The tendency for a higher initial load of DM and starch in birds without oat
hulls seems to support the hypothesis that one important function of the gizzard
is feed-flow regulation. 6. In conclusion, the anterior digestive tract seems to
have an important regulative function in broiler chickens when stimulated by
intermittent feeding or structural components. More research is needed in order
to elucidate the role of the crop and gizzard for phytase function.
PMID- 28503930
TI - Impact of a Plant-Based Diet and Support on Mitigating Type 2 Diabetes Mellitus
in Latinos Living in Medically Underserved Areas.
AB - PURPOSE: To determine the impact that a high-fiber, low-fat diet, derived from
mostly plant-based sources, when coupled with support has upon self-management of
type 2 diabetes mellitus in Latinos from medically underserved areas (MUAs).
DESIGN: Experimental randomized controlled community pilot study. SETTING: Three
community clinics in MUAs located within San Bernardino County, California.
PARTICIPANTS: Thirty-two randomly assigned Latinos with A1C greater than 6.4: 15
control and 17 experimental. INTERVENTION: Participants completed a 5-week
education program. Researchers provided follow-up support for 17 randomly
assigned experimental group participants through focus groups held at
participating clinics-1, 3, and 6 months posteducation. MEASURES: Changes in fat
and fiber consumption were measured using a modified Dietary Screener for Mexican
Americans. Self-management was measured through the Self-Efficacy for Exercise
Scale and Diabetes Quality of Life Measure. ANALYSIS: Baseline characteristics
for both groups were analyzed using independent t tests and chi2 tests. A 2-way
repeated-measures analysis of variance was used to analyze biometric data between
baseline and 6 months for both groups. RESULTS: Mean A1C levels decreased from
baseline to 6 months for both groups: control, MU1 = 9.57, MU2 = 9.49;
experimental, MU1 = 8.53, MU2 = 7.31. CONCLUSION: The experimental group
demonstrated a statistically significant reduction in mean A1C levels ( P = .002)
when compared to the control group.
PMID- 28503931
TI - Burnout among healthcare workers at L'Aquila: its prevalence and associated
factors.
AB - Burnout, which is now recognized as a real problem in terms of its negative
outcome on healthcare efficiency, is a stress condition that can be increased by
exposure to natural disasters, such as the 2009 L'Aquila earthquake. This study
aims to evaluate burnout syndrome, its associated risk factors and stress levels,
and the individual coping strategies among healthcare professionals at L'Aquila
General Hospital. A cross-sectional study of 190 healthcare workers was
conducted. There was a questionnaire for the collection of the socio-demographic,
occupational and anamnestic data, and the Maslach Burnout Inventory, the General
Health Questionnaire-12 items (GHQ-12) and the Brief COPE were used. The burnout
dimensions showed high scores in Emotional Exhaustion (38.95%), in
Depersonalization (23.68%) and in lack of Personal Accomplishment (23.16%), along
with the presence of moderate to high levels of distress (54.21%). In addition to
factors already known to be associated with burnout (job perception and high
levels of distress) exposure to an earthquake emerged as a factor independently
associated with the syndrome. Adaptive coping strategies such as religiosity
showed a significant and negative relationship with burnout. Our research
highlights the need for interventions directed at a reduction in workload and
work-stressors and an improvement of adaptive coping strategies, especially in a
post-disaster workplace.
PMID- 28503932
TI - Maladaptive Personality Trait Models: Validating the Five-Factor Model
Maladaptive Trait Measures With the Personality Inventory for DSM-5 and NEO
Personality Inventory.
AB - Eight measures have been developed to assess maladaptive variants of the five
factor model (FFM) facets specific to personality disorders (e.g., Five-Factor
Borderline Inventory [FFBI]). These measures can be used in their entirety or as
facet-based scales (e.g., FFBI Affective Dysregulation) to improve the
comprehensiveness of assessment of pathological personality. There are a limited
number of studies examining these scales with other measures of similar traits
(e.g., DSM-5 alternative model). The current study examined the FFM maladaptive
scales in relation to the respective general personality traits of the NEO
Personality Inventory-Revised and the pathological personality traits of the DSM
5 alternative model using the Personality Inventory for DSM-5. The results
indicated the FFM maladaptive trait scales predominantly converged with
corresponding NEO Personality Inventory-Revised, and Personality Inventory for
DSM-5 traits, providing further validity for these measures as extensions of
general personality traits and evidence for their relation to the pathological
trait model. Benefits and applications of the FFM maladaptive scales in clinical
and research settings are discussed.
PMID- 28503929
TI - Rare Control of SIVmac239 Infection in a Vaccinated Rhesus Macaque.
AB - Effector memory T cell (TEM) responses display potent antiviral properties and
have been linked to stringent control of simian immunodeficiency virus (SIV)
replication. Since recurrent antigen stimulation drives the differentiation of
CD8+ T cells toward the TEM phenotype, in this study we incorporated a persistent
herpesviral vector into a heterologous prime/boost/boost vaccine approach to
maximize the induction of TEM responses. This new regimen resulted in CD8+ TEM
biased responses in four rhesus macaques, three of which controlled viral
replication to <1,000 viral RNA copies/ml of plasma for more than 6 months after
infection with SIVmac239. Over the course of this study, we made a series of
interesting observations in one of these successful controller animals. Indeed,
in vivo elimination of CD8alphabeta+ T cells using a new CD8beta-depleting
antibody did not abrogate virologic control in this monkey. Only after its
CD8alpha+ lymphocytes were depleted did SIV rebound, suggesting that
CD8alphaalpha+ but not CD8alphabeta+ cells were controlling viral replication. By
2 weeks postinfection (PI), the only SIV sequences that could be detected in this
animal harbored a small in-frame deletion in nef affecting six amino acids. Deep
sequencing of the SIVmac239 challenge stock revealed no evidence of this
polymorphism. However, sequencing of the rebound virus following CD8alpha
depletion at week 38.4 PI again revealed only the six-amino acid deletion in nef.
While any role for immunological pressure on the selection of this deleted
variant remains uncertain, our data provide anecdotal evidence that control of
SIV replication can be maintained without an intact CD8alphabeta+ T cell
compartment.
PMID- 28503934
TI - Score Disparity Between the MMSE and the SLUMS.
AB - BACKGROUND: Multiple brief cognitive instruments are available to assess
cognitive impairment in older adults. However, not all instruments demonstrate
the same effectiveness when utilized with higher educated adults. This study
evaluates the score disparity between the Mini-Mental State Examination (MMSE)
and the St. Louis University Mental Status (SLUMS) Examination across the
education spectrum. It was hypothesized that individuals with more years of
formal education would produce higher scores on both the MMSE and SLUMS. Previous
research was conducted to create a conversion scale used to compare and convert
the MMSE scores to SLUMS scores. This research study provides additional data to
add to the body of knowledge regarding a conversion scale for the MMSE and SLUMS.
METHODS: Seventy-five adults older than the age of 60 years were each
administered the MMSE and SLUMS. RESULTS: Contrary to our hypothesis, individuals
with more years of formal education did not produce significantly greater scores
on the MMSE or SLUMS. Likewise, education level analyzed as a continuous measure
was not significantly correlated with the MMSE, r(75) = -0.191, or SLUMS, r(75) =
0.019. Interestingly, among participants with a high (but not low) education
level, there was a marginal but significant difference in mean score between the
MMSE (29.00 +/- 1.47) and SLUMS (27.74 +/- 3.08), t(64) = 3.70, P < .001.
CONCLUSION: Other factors besides education may impact the performance of older
adults on the MMSE and SLUMS, but it does appear that education level may
moderate the score disparity between the 2 instruments. Additional studies are
needed before using the MMSE to predict the score on the SLUMS and vice versa.
PMID- 28503935
TI - Personality Inventory for DSM-5 (PID-5) in Clinical Versus Nonclinical
Individuals: Generalizability of Psychometric Features.
AB - The Personality Inventory for Diagnostic and Statistical Manual of Mental
Disorders-Fifth Edition (PID-5) was developed for the assessment of pathological
traits in clinical settings. However, most research on the PID-5 is derived from
nonclinical samples. To date, the comparability and generalizability of PID-5
constructs across nonclinical and clinical samples have not been adequately
investigated. Therefore, we investigated the measurement invariance, five-factor
structure, and factor correlations across clinical and nonclinical samples. The
clinical sample ( n = 598) comprised patients with nonpsychotic disorders (81%
women; mean age = 28.95), whereas a matched nonclinical sample ( n = 598)
comprised community-dwelling individuals (81% women; mean age = 29.59).
Measurement invariance was analyzed using a 13-step, two-group exploratory
structural equation modeling approach. The results demonstrated acceptable
psychometric properties for both samples and supported strong measurement
invariance across the groups at the domain level.
PMID- 28503933
TI - Highly Human Immunodeficiency Virus-Exposed Seronegative Men Have Lower Mucosal
Innate Immune Reactivity.
AB - Risk of HIV acquisition varies, and some individuals are highly HIV-1-exposed,
yet, persistently seronegative (HESN). The immunologic mechanisms contributing to
this phenomenon are an area of intense interest. As immune activation and
inflammation facilitate disease progression in HIV-1-infected persons and
gastrointestinal-associated lymphoid tissue is a highly susceptible site for
transmission, we hypothesized that reduced gut mucosal immune reactivity may
contribute to reduced HIV-1 susceptibility in HESN men with a history of numerous
rectal sexual exposures. To test this, we used ex vivo mucosal explants from
freshly acquired colorectal biopsies from healthy control and HESN subjects who
were stimulated with specific innate immune ligands and inactivated whole
pathogens. Immune reactivity was then assessed via cytokine arrays and proteomic
analysis. Mucosal immune cell compositions were quantified via
immunohistochemistry. We found that explants from HESN subjects produced less
proinflammatory cytokines compared with controls following innate immune
stimulation; while noninflammatory cytokines were similar between groups.
Proteomic analysis identified several immune response proteins to be
differentially expressed between HIV-1-stimulated HESN and control explants.
Immunohistochemical examination of colorectal mucosa showed similar amounts of T
cells, macrophages, and dendritic cells between groups. The results of this pilot
study suggest that mucosal innate immune reactivity is dampened in HESN versus
control groups, despite presence of similar densities of immune cells in the
colorectal mucosa. This observed modulation of the rectal mucosal immune response
may contribute to lower risk of mucosal HIV-1 transmission in these individuals.
PMID- 28503936
TI - Immune responses following experimental infection with Ascaridia galli and
necrotic enteritis in broiler chickens.
AB - Broilers commonly suffer from necrotic enteritis (NE). Other gastrointestinal
infectious diseases affect poultry, including nematode infections which are
considered a re-emerging disease in barn and free-range systems. The aim of this
study was to characterize the immune response of broilers after artificial
infection with NE and contrast these with responses to the nematode Ascaridia
galli and determine whether immune parameters measured during the course of
infection can be used to distinguish infected from uninfected birds. A total of
96 one-day-old male Ross 308 broiler chickens were used in this study. At 10 days
of age, broilers were randomly assigned to one of the following treatment groups:
control birds (n = 32), A. galli infected birds (n = 32), or NE infected birds (n
= 32) and inoculated with the appropriate infective agents. The immune response
of birds was monitored through evaluation of haematology parameters, acute phase
protein production, and intraepithelial intestinal lymphocyte population changes
at 11, 16, 20, and 32 days of age. T-helper cells (CD4+CD8-) increased
significantly over time, and were significantly higher in A. galli and NE
compared to day 10 controls. In conclusion, alpha-1 glycoprotein levels can
distinguish birds with NE from other birds, including those infected with A.
galli; also T-helper cell numbers can distinguish both NE and A. galli from
uninfected birds and thirdly, 10 days post infection is the best time point to
evaluate the bird's immune response for A. galli infections.
PMID- 28503937
TI - Assessment of tricalcium phosphate/collagen (TCP/collagene)nanocomposite scaffold
compared with hydroxyapatite (HA) on healing of segmental femur bone defect in
rabbits.
AB - Bone regeneration is an important objective in clinical practice and has been
used for different applications. The aim of this study was to evaluate the
effectiveness of nanocomposite tricalcium phosphate (TCP)/collagen scaffolds
combined with hydroxyapatite scaffold for bone healing in surgery of femoral
defects in rabbits. In this study, 45 mature male New Zealand white rabbits
between 6 and 8 months old and weighting between 3 and 3.5 kg were examined.
Rabbits were divided into three groups. Surgical procedures were performed after
intramuscular injection of Ketamine 10% (ketamine hydrochloride, 50 mg/kg) and
Rompun 5% (xylazine, 5 mg/kg). Then an approximately 6 mm diameter-5 mm cylinder
bone defect was created in the femur of one of the hind limbs. After inducing the
surgical wound, all rabbits were coloured and randomly divided into three
experimental groups of 15 animals each. Group 1 received pure medical
nanocomposite TCP/collagen granules, group 2 received hydroxyapatite, and third
group was a control group which received no treatment. Histopathological
evaluation was performed on days 15, 30, and 45 after surgery. On days 15, 30,
and 45 after surgery, the quantity and the velocity of stages of bone formation
at the healing site in nanocomposite TCP/collagen group were better than HA and
control groups and the quantity of newly formed lamellar bone at the healing site
in nanocomposite TCP/collagen group were better than onward compared with HA and
control groups. In conclusion, it seems that TCP/collagen nanocomposite has a
significant role in the reconstruction of bone defects and can be used as
scaffold in bone fractures.
PMID- 28503938
TI - Design and synthesis of 2-substituted-5-(4-trifluoromethylphenyl
sulphonamido)benzoxazole derivatives as human GST P1-1 inhibitors.
AB - The glutathione transferases (GSTs) are a family of widely distributed Phase II
detoxification enzymes. GST P1-1 is frequently overexpressed in rat and human
tumours. It is suggested that overexpression of hGST P1-1 by human tumor cells
may play a role in resistance to cancer chemotherapy. Hence, hGST P1-1 can be a
promising target for cancer treatment. In this study, new hGST P1-1 inhibitors, 2
(4-substitutedphenyl/benzyl)-5-(4-trifluoromethylphenylsulphonamido) benzoxazole
derivatives (Va-Vk) have been designed and synthesized. Surprisingly, in vitro
hGST P1-1 enzyme inhibition studies demonstrated that all of the tested compounds
except Vj had better activity than the reference drug EA and it is also
correlated with the docking results. Additionally we compared the interactions
with hGST P1-1 enzyme of newly synthesized compound Vh (bearing CF3 group) and
previously synthesized compound 5f (bearing NO2 group). According to the docking
results, compound Vh bound to the hGST P1-1 enzyme with a higher affinity
compared to 5f. Therefore, we can consider that these data make a sense and can
explain its higher activity. The compounds that obtained from this research could
be used as scaffolds in design of new potent hGST P1-1 inhibitors useful in the
treatment of the resistance of cancer chemotherapy.
PMID- 28503940
TI - Matrix solid-phase dispersion as a tool for phytochemical and bioactivities
characterisation: Crataegus oxyacantha L._A case study.
AB - The use of a matrix solid-phase dispersion (MSPD) process to extract polyphenols
from hawthorn (Crataegus oxyacantha L.) a deciduous shrub with an expected rich
phytochemical profile, has been evaluated. MSPD extracts of fruits and leaves
have an outstanding content of polyphenols, although the particular phenolic
profile is solvent dependent. The extracts were analysed by HPLC-DAD for the
accurate identification of the major bioactive polyphenols, some of which have
never been described for this species. MSPD has proven to be a good alternative
to the classic methods of obtaining natural extracts, fast and with low
consumption of organic solvents, therefore, environmentally friendly. The
bioactivities can be considered also very remarkable, revealing extracts with
high levels of antioxidant activity.
PMID- 28503939
TI - Clarification of Eponymous Anatomical Terminology: Structures Named After Dr
Geoffrey V. Osborne That Compress the Ulnar Nerve at the Elbow.
AB - BACKGROUND: In 1957, Dr Geoffrey Osborne described a structure between the medial
epicondyle and the olecranon that placed excessive pressure on the ulnar nerve.
Three terms associated with such structures have emerged: Osborne's band,
Osborne's ligament, and Osborne's fascia. As anatomical language moves away from
eponymous terminology for descriptive, consistent nomenclature, we find
discrepancies in the use of anatomic terms. This review clarifies the definitions
of the above 3 terms. METHODS: We conducted an extensive electronic search via
PubMed and Google Scholar to identify key anatomical and surgical texts that
describe ulnar nerve compression at the elbow. We searched the following terms
separately and in combination: "Osborne's band," "Osborne's ligament," and
"Osborne's fascia." A total of 36 papers were included from 1957 to 2016.
RESULTS: Osborne's band, Osborne's ligament, and Osborne's fascia were found to
inconsistently describe the etiology of ulnar neuritis, referring either to the
connective tissue between the 2 heads of the flexor carpi ulnaris muscle as
described by Dr Osborne or to the anatomically distinct fibrous tissue between
the olecranon process of the ulna and the medial epicondyle of the humerus.
CONCLUSIONS: The use of eponymous terms to describe ulnar pathology of the elbow
remains common, and although these terms allude to the rich history of surgical
anatomy, these nonspecific descriptions lead to inconsistencies. As Osborne's
band, Osborne's ligament, and Osborne's fascia are not used consistently across
the literature, this research demonstrates the need for improved terminology to
provide reliable interpretation of these terms among surgeons.
PMID- 28503941
TI - Pyrrolo[2,1-a]isoquinoline and pyrrole alkaloids from Sinomenium acutum.
AB - Two pyrrolo[2,1-a]isoquinolines (1 and 2) and three pyrrole alkaloids (3-5),
including three new ones, named sinopyrines A-C (1-3), were isolated from the 95%
EtOH extract of the stems and rhizomes of Sinomenium acutum (Thumb.) Rehd. et
Wils. The structures of the new compounds were elucidated on the basis of
spectroscopic data. This is the first report of pyrrole-bearing natural compounds
from the family Menispermaceae.
PMID- 28503942
TI - Optimisation of steam distillation extraction oil from onion by response surface
methodology and its chemical composition.
AB - Oil extraction from onion was performed by steam distillation. Response surface
methodology was applied to evaluate the effects of ratio of water to raw
material, extraction time, zymolysis temperature and distillation times on yield
of onion oil. The maximum extraction yield (1.779%) was obtained as following
conditions: ratio of water to raw material was 1, extraction time was 2.5 h,
zymolysis temperature was 36 degrees and distillation time was 2.6 h. The
experimental values agreed well with those predicted by regression model. The
chemical composition of extracted onion oil under the optimum conditions was
analysed by gas chromatography-mass spectrometry technology. The results showed
that sulphur compounds, like alkanes, sulphide, alkenes, ester and alcohol, were
the major components of onion oil.
PMID- 28503944
TI - miR-133 involves in lung adenocarcinoma cell metastasis by targeting FLOT2.
AB - BACKGROUND: Dysregulated microRNAs (miRNAs) reported to involve into the
oncogenesis and progression in various human cancers. However, the roles and
mechanism of miR-133 in lung adenocarcinoma remain largely unclear. METHODS: In
this study, qPCR assay and western blot were used to detect the expression levels
of miR-133, Akt and FLOT2. Luciferase reporter assay was used to identify the
target role of miR-133 on FLOT2. The cell invasion and the migration capability
were performed using the transwell invasion assay and wound healing assay.
RESULTS: We found that miR-133 expression levels were downregulated in human lung
adenocarcinoma specimens and cell lines compared with the adjacent normal tissues
and normal human bronchial epithelial cell. miR-133 significantly suppressed
metastasis of lung adenocarcinoma cells in vitro. Furthermore, FLOT2 (flotillin
2) identified as a direct target of miR-133, and FLOT2 expression levels were
inversely correlated with miR-133 expression levels in human lung adenocarcinoma
specimens. And the restoration studies suggested FGF2 as a downstream effector of
miR-133 which acted through Akt signalling pathway. CONCLUSIONS: Our study
revealed the mechanism that miR-133 suppresses lung adenocarcinoma metastasis by
targeting FLOT2 via Akt signalling pathway, implicating a potential prognostic
biomarker and therapeutic target for lung adenocarcinoma treatment.
PMID- 28503943
TI - Transcriptional profile of ethylene glycol monomethyl ether-induced testicular
toxicity in rats.
AB - To clarify the molecular mechanism of ethylene glycol monomethyl ether (EGME)
induced testicular toxicity, the potential for EGME-related changes in transcript
levels of genes including spermatocyte-specific genes was evaluated in the testis
of rats given single dosing of EGME at 200, 600, or 2000 mg/kg. Furthermore, the
contribution of decreased testicular testosterone on EGME-induced spermatocyte
toxicity was investigated by comparing to transcriptional profile due to a
testosterone synthesis inhibitor, ketoconazole (KET), at 30 or 300 mg/kg. EGME at
600 mg/kg or more dose-dependently caused testicular toxicity characterized by
degeneration and necrosis of spermatocytes at stage VII-XIV seminiferous tubules.
The spermatocyte injury was well correlated with decreased spermatocyte-specific
gene expression. Analysis of upstream regulators by the Ingenuity Pathways
Analysis system suggested that up-regulation of oxidative stress, protein kinase
activation, and histone acetylation was involved in EGME-induced spermatocyte
toxicity. Interestingly, KET decreased testicular testosterone to a similar
extent compared to the EGME treatment, but KET at up to 300 mg/kg did not show
any histopathological abnormality or change in the expression of spermatocyte
specific genes. These results suggested that the decreased testicular
testosterone have little impact on EGME-induced spermatocyte injury. In contrast,
KET showed trends toward increases in Hsd3b2 and Hsd17b2 mRNAs, presumably
resulting from inhibition of androgen synthesis. Transcriptome analysis clearly
demonstrated the differential effects of EGME and KET on androgen synthesis. In
conclusion, EGME caused spermatocyte toxicity correlated with decreased
expression of spermatocyte-specific genes. Furthermore, oxidative stress, protein
kinase activation, and histone acetylation were suggested to be involved in EGME
induced testicular toxicity.
PMID- 28503945
TI - A new ribonucleotide from Cordyceps militaris.
AB - One new ribonucleotide, 5'-(3''-deoxy-beta-D-ribofuranosyl)-3'-deoxyadenosine
(1), and 14 known compounds (2-15) were isolated from an ethanol extract of
Cordyceps militaris. The chemical structures of these compounds were determined
from 1D and 2D NMR (1H-1H COSY, HMBC, HMQC and NOESY) and HR-ESI-MS spectra, and
results were compared with data from the literature. The effects of all isolated
compounds were measured on NF-kappaB activation, with compound 2 exhibiting
significant inhibitory activity against TNF-alpha-induced NF-kappaB reporter gene
expression in HeLa cells from 3 to 100 MUM.
PMID- 28503946
TI - Fractional CO2 laser therapy: a new challenge for vulvovaginal atrophy in
postmenopausal women.
AB - OBJECTIVE: To evaluate the effects of CO2 laser in the treatment of vulvovaginal
atrophy (VVA) in postmenopausal women. METHODS: VVA was assessed in 87
postmenopausal women (mean age 58.6 +/- 6.9 years) before and after the
treatment. The protocol consisted of three monthly treatments and included the
treatment of vulva. Subjective measures included VAS (Visual Analog Scale) both
for vaginal dryness and dyspareunia; DIVA (Day-by-day Impact of Vaginal Aging); a
questionnaire on treatment satisfaction and one about the degree of pain during
the procedure. Objective measures included VHI (Vaginal Health Index) and VVHI
(Vulvo-Vaginal Health Index). Time points of the study were at the screening
visit (T0), at baseline (T1), at week 4 (T2), at week 8 (T3), after 3 months
since the last laser application (T4), after 6 months (T5), after 9 months (T6),
after 12 months (T7) and after 15 months (T8). RESULTS: Treatment induced
significant improvement in the VAS score. After treatment, VHI and VVHI indicated
no VVA and this improvement was long lasting. Multivariate analysis showed that
the time of follow-up was correlated with better VHI and VVHI (p < 0.001). DIVA
improved over time (p < 0.001). CONCLUSIONS: This study shows that CO2 laser
treatment induces a significant and long-lasting improvement of symptoms.
PMID- 28503947
TI - Recommendations for data monitoring committees from the Clinical Trials
Transformation Initiative.
AB - Background/aims Use of data monitoring committees to oversee clinical trials was
first proposed nearly 50 years ago. Since then, data monitoring committee use in
clinical trials has increased and evolved. Nonetheless, there are no well-defined
criteria for determining the need for a data monitoring committee, and
considerable variability exists in data monitoring committee composition and
conduct. To understand and describe the role and function of data monitoring
committees, and establish best practices for data monitoring committee trial
oversight, the Clinical Trials Transformation Initiative-a public-private
partnership to improve clinical trials-launched a multi-stakeholder project.
Methods The data monitoring committee project team included 16 individuals
charged with (1) clarifying the purpose of data monitoring committees, (2)
identifying best practices for independent data monitoring committee conduct, (3)
describing effective communication practices, and (4) developing strategies for
training data monitoring committee members. Evidence gathering included a survey,
a series of focus group discussions, and a 2-day expert meeting aimed at
achieving consensus opinions that form the foundation of our data monitoring
committee recommendations. Results We define the role of the data monitoring
committee as an advisor to the research sponsor on whether to continue, modify,
or terminate a trial based on periodic assessment of trial data. Data monitoring
committees should remain independent from the sponsor and be composed of members
with no relevant conflicts of interest. Representation on a data monitoring
committee generally should include at least one clinician with expertise in the
therapeutic area being studied, a biostatistician, and a designated chairperson
who has experience with clinical trials and data monitoring. Data monitoring
committee meetings are held periodically to evaluate the unmasked data from
ongoing trials, but the content and conduct of meetings may vary depending on
specific goals or topics for deliberation. To guide data monitoring committee
conduct and communication plans, a charter consistent with the protocol's
research design and statistical analysis plan should be developed and agreed upon
by the sponsor and the data monitoring committee prior to patient enrollment. We
recommend concise and flexible charters that explain roles, responsibilities,
operational issues, and how data monitoring committee recommendations are
generated and communicated. The demand for data monitoring committee members
appears to exceed the current pool of qualified individuals. To prepare a new
generation of trained data monitoring committee members, we encourage a
combination of didactic educational programs, practical experience, and skill
development through apprenticeships and mentoring by experienced data monitoring
committee members. Conclusion Our recommendations address data monitoring
committee use, conduct, communication practices, and member preparation and
training. Furthermore recommendations form the foundation for ongoing efforts to
improve clinical trial oversight and enhance the safety and integrity of clinical
research. These recommendations serve as a call to action for implementation of
best practices that benefit study participants, study sponsors, and society.
PMID- 28503948
TI - Attraction behaviour of Anagrus nilaparvatae to remote lemongrass (Cymbopogon
distans) oil and its volatile compounds.
AB - Utilisation of Anagrus nilaparvatae is a promising and effective method for
planthoppers manipulation. Twenty-seven components of remote lemongrass
(Cymbopogon distans) oil were identified by GC/MS and nine volatiles were
selected for behavioural experiments. In this study, we noted that the remote
lemongrass oil was attractive to female A. nilaparvatae at concentrations of 0.1
and 1 mg/L. alpha-Pinene, beta-pinene, eucalyptol, carveol and D-carvone
attracted female wasps in the dose-dependent bioassays. Blend 1 (a mixture of
eucalyptol, D-carvone, carveol, alpha-pinene, and beta-pinene with ratios of
remote lemongrass oil volatiles of 625:80:11:5:3) attracted female wasps at 10
mg/L, while blend 2 (a mixture of the same five volatiles at the same loading
ratio) attracted them at 0.1 and 1 mg/L. These results suggested that plant
essential oils could be attractants for natural enemies to control pests. The
ratios of volatiles in the mixtures affect the attractiveness of the synthetic
mixtures.
PMID- 28503949
TI - Silymarin nanoemulsion against human hepatocellular carcinoma: development and
optimization.
AB - OBJECTIVE: Nanoemulsion of silymarin was developed and optimized. MATERIALS AND
METHODS: Nanoemulsion was made by aqueous titration method. Sefsol 218 (5.8%
v/v), Kolliphor RH40 and polyethylene glycol 400 (Smix; 2:1; 28.99% v/v) were
used as oil phase, surfactant and co-surfactant while distilled water (65.22%
v/v) acted as an aqueous phase. Nanoemulsion was characterized on the basis of
particle size, viscosity, electrical conductivity and refractive index. Further,
in vitro release, in vivo pharmacokinetic study, stability study and cancer cell
line studies were also performed. RESULTS AND DISCUSSION: The optimized
formulation (NE9) with mean particle size of 21.24 nm showed a minimum viscosity
of 9.59 cps, maximum drug release (97.75%) in 24 h. The NE9 formulation also
showed higher AUC (p < .01) and Cmax (p < .01) and shorter Tmax (p < .05)
compared with conventional and standard suspensions of silymarin. The stability
study also showed considerably stable formulations at refrigerator temperature as
compared with room temperature (p > .05). The cancer cell line studies also
confirmed that silymarin nanoemulsion reduced the cell viability and increased
ROS intensity and chromatin condensation (p < .05). CONCLUSION: Our results
concluded that nanoemulsion may be an efficient carrier for oral delivery of
silymarin against human hepatocellular carcinoma without damaging normal cells.
PMID- 28503950
TI - The effects of rapeseed meal and legume seeds as substitutes for soybean meal on
productivity and gastrointestinal function in rabbits.
AB - The aim of this study was to determine the effects of soybean meal (SBM)
substitution by a mixture of rapeseed meal (RSM), white lupine seeds (WLS) and
pea seeds (PS) on productivity, nutrient digestibility, nitrogen retention and
gastrointestinal function in Hyplus rabbits. The Control diet (SBM15) contained
15% SBM, whereas Diet SBM7.5 contained 7.5% SBM, 5% RSM, 4% WLS and 3% PS. In
Diet SBM0, SBM was completely replaced by RSM, WLS and PS (10%, 8% and 6%,
respectively). A production trial was performed on 90 Hyplus rabbits aged from 35
to 84 d (45 each sex; 953 +/- 4.6 g). A digestion and balance trial was conducted
on 30 rabbits. Additionally, several parameters of the gastrointestinal tracts
from eight animals from each group were analysed, where special attention was
paid to the enzymatic activity of microbiota and the short-chain fatty acids
concentration in caecum and colon. The experimental diets did not cause
significant differences regarding performance parameters evaluated in vivo and
post-mortem, and in the nutrient and energy digestibility or nitrogen retention.
The observed changes in the enzymatic activity of large gut microbiota, including
the selective increase in secretion of glycoside hydrolases by bacterial cells,
seem to be responsible for the unchanged growth performance of rabbits fed diets
where SBM was substituted by a mixture of RSM, WLS and PS. The obtained results
indicate that in rabbit diets SBM may be, partially or completely, successfully
replaced by a feed mixture of RSM, WLS and PS.
PMID- 28503951
TI - Gold nanoparticles applications: from artificial enzyme till drug delivery.
AB - Today, nano-medicine promotes new therapeutics and diagnostics tools, including
sensing of biomolecules as a biosensor, cancer chemotherapy and drug or gene
delivery. Because of small size and biocompatibility of gold nanoparticles
(GNPs), they become a good candidate for biological application. Also, thanks to
their biological and chemical properties, they can mimic function of some enzymes
including super oxide dismutase (SOD), esterase, etc. Also, biomaterials and
bioengineering have grown so fast since the last decade for many therapeutic
applications such as tissue regeneration. Among these cutting edge technology,
nanomaterials find the way to becoming a very powerful tool for using in many
fields of researchers including biosensing, gene therapy and chemotherapy. In
this review, we focused on some biological applications of GNPs in biology and
medicine.
PMID- 28503952
TI - Hyaluronic acid/polyethylene glycol nanoparticles for controlled delivery of
mitoxantrone.
AB - Hyaluronic acid (HA) has inherent ability to target the CD44 receptors and
internalize into tumour cells via receptor-mediated endocytosis. Therefore,
conjugation of this natural linear polysaccharide to polymeric NPs or micelles,
as one of the most promising approaches, could be useful for future clinical
applications such as drug delivery. Accordingly, we report on the synthesis of
mitoxantrone (MTX)-conjugated polymeric nanoparticles (NPs) composed of
polyethylene glycol-HA (PEG-HA) for MTX delivery toward special tumour cells. To
determine the size of the polymeric NPs, field emission scanning electron
microscopy (FESEM) and particle size analyzer system Zetasizer_nanoZS were
employed. The in vitro cytotoxicity analysis of MTX-loaded HA-PEG NPs and free
MTX against two cell lines with different levels of CD44 expression (MDA-MB-231
(very high) and MCF-7 (low) was conducted by MTT assay. Also, computational
molecular docking was employed to study in detail the active site residues and
the critical interactions between HA-EDA-PEG-EDA-MTX NPs and CD44 receptor. The
particle size analysis and electron microscopy showed the average size of
polymeric NPs less than 350 nm. FT-IR spectrophotometry analysis and also NMR
confirmed the conjugation of HA and MTX onto the PEG. Cytotoxicity assay revealed
that the engineered polymeric NPs were able to specifically bind to and
significantly inhibit the CD44 receptor-positive MDA-MB-231 cells, but not the
CD44-negative MCF-7 cells. Furthermore, analysis of the binding modes revealed
that for the best-docked pose nearly 10 conventional hydrogen bond can occur
between the MTX-EDA-PEG-EDA-HA NPs and amino acids of CD44 receptor. Based on
these findings, we suggest the HA-PEG-MTX NPs as an effective functional-targeted
nanomedicine toward therapy of CD44-positive cancers.
PMID- 28503953
TI - Effect of deltamethrin and fluoride co-exposure on the brain antioxidant status
and cholinesterase activity in Wistar rats.
AB - The study evaluated the effect of commercial preparation of deltamethrin,
Butox(r), and fluoride (F-) co-exposure on the brain antioxidant status and
cholinesterase activity in rats. Group A was untreated. Group B was gavaged
Butox(r), providing deltamethrin at the dose rate of 1.28 mg per kg body weight
per day. Group C was administered F-, as NaF, in drinking water providing 20 ppm
F-. Group D received both deltamethrin and F- at the same dosages as groups B and
C, respectively. Although, glutathione S-transferase activity was induced only in
Butox(r) alone treated group, the activities of superoxide dismutase and catalase
were inhibited in all treatment groups when compared to the control group.
Elevated lipid peroxidation was observed in the groups exposed to F-. The
activity of erythrocyte acetylcholinesterase (AChE) was inhibited in Butox(r)
treated groups, whereas brain AChE activity was inhibited in all treatment
groups. In conclusion, both deltamethrin (given as Butox(r)) and F- inhibit AChE
activity and produce oxidative stress in brain with F- producing more oxidative
damage. However, compared to the individual exposures, the co-exposure of these
chemicals does not produce any exacerbated alteration in these biochemical
parameters.
PMID- 28503954
TI - Experiences of employment among young people with juvenile idiopathic arthritis:
a qualitative study.
AB - PURPOSE: This study explored expectations and experiences of employment among
young people with juvenile idiopathic arthritis and the role of health
professionals in promoting positive employment outcomes. METHODS: Semistructured
interviews (n = 13) and three focus groups (n = 9, n = 4, n = 3) were conducted
with young people (16-25 y) and adults (26-31 y) with juvenile idiopathic
arthritis and semistructured interviews (n = 9) were conducted with health
professionals. Transcripts were analyzed thematically. RESULTS: Young people with
juvenile idiopathic arthritis have concerns about employers' attitudes toward
employees with long-term health conditions and lack knowledge of
antidiscrimination legislation. Young people not in education, employment or
training identify arthritis as a key barrier. Challenges associated with
arthritis (e.g., pain, psychological distress) may not be visible to employers.
Decisions about disclosing arthritis are challenging and cause anxiety. Young
people associate good disease management and access to flexible and convenient
care with their capacity to succeed in employment. Psychosocial and vocational
interventions have benefited some young people but are not routinely available.
CONCLUSIONS: Low expectations of employers may affect young people's decisions
about disclosure and seeking appropriate support in the work place. Health
professionals can equip young people with knowledge and skills to negotiate
appropriate support, through signposting to antidiscrimination information and
offering practice of transferable skills such as disclosure in consultations.
Implications for rehabilitation Young people with juvenile idiopathic arthritis
encounter challenges with regard to employment; many lack the knowledge and
skills to negotiate appropriate support from employers. Rehabilitation
professionals could play a more substantial role in equipping them with relevant
knowledge and skills by signposting to antidiscrimination information and
nurturing transferable skills, such as disclosure, in consultations. Potentially
helpful interventions, such as group activities or assessment by a psychologist,
have benefited some but need more evaluative scrutiny with respect to employment
outcomes.
PMID- 28503956
TI - Sacituzumab govitecan: an antibody-drug conjugate.
AB - INTRODUCTION: Despite advances in the diagnosis and treatment of patients with
cancer, patients with metastatic cancer have limited therapeutic options after
initial lines of therapy. Understanding tumor biology has translated into the
identification of actionable targets that resulted in therapeutics. Antibody-drug
conjugates (ADC) are capitalizing on this explosion of scientific information.
ADCs allow an antibody to a unique target to be conjugated via an innovative
linker, to a highly toxic drug which is delivered to its target. Sacituzumab
govitecan is an ADC that combines the active molecule in irinotecan, SN-38, to an
antibody targeting trop2. Areas covered: In this review, the authors introduce
the reader to the ADC sacituzumab govitecan providing the reader with details
about its pharmacokinetics, pharmacodynamics, efficacy and safety. The authors
also give their expert analysis about its potential future use. Expert opinion:
Sacituzumab govitecan is a novel and well-tolerated therapeutic showing promising
results in difficult to treat cancers. Further studies are underway to optimize
the group of patients that would benefit from it. Given its excellent
performance, we are cautiously optimistic it will be approved by the FDA.
PMID- 28503955
TI - New insights into the earliest stages of colorectal tumorigenesis.
AB - INTRODUCTION: Tumors in the large intestine have been postulated to arise via a
stepwise accumulation of mutations, a process that takes up to 20 years. Recent
advances in lineage tracing and DNA sequencing, however, are revealing new
evolutionary models that better explain the vast amount of heterogeneity observed
within and across colorectal tumors. Areas covered: A review of the literature
supporting a novel model of colorectal tumor evolution was conducted. The
following commentary examines the basic science and clinical evidence supporting
a modified view of tumor initiation and progression in the colon. Expert
commentary: The proposed 'cancer punctuated equilibrium' model of tumor evolution
better explains the variability seen within and across polyps of the colon and
rectum. Small colorectal polyps (6-9mm) followed longitudinally by interval
imaging with CT colonography have been reported to have multiple fates: some
growing, some remaining static in size, and others regressing in size over time.
This new model allows for this variability in growth behavior and supports the
hypothesis that some tumors can be 'born to be bad' as originally postulated by
Sottoriva and colleagues, with very early molecular events impacting tumor
fitness and growth behavior in the later stages of the disease process.
PMID- 28503957
TI - A model for developing disability confidence.
AB - PURPOSE: Many clinicians, educators, and employers lack disability confidence
which can affect their interactions with, and inclusion of people with
disabilities. Our objective was to explore how disability confidence developed
among youth who volunteered with children who have a disability. METHODS: We
conducted 30 in-depth interviews (16 without a disability, 14 with disabilities),
with youth aged 15-25. We analyzed our data using an interpretive, qualitative,
thematic approach. RESULTS: We identified four main themes that led to the
progression of disability confidence including: (1) "disability discomfort,"
referring to lacking knowledge about disability and experiencing unease around
people with disabilities; (2) "reaching beyond comfort zone" where participants
increased their understanding of disability and became sensitized to difference;
(3) "broadened perspectives" where youth gained exposure to people with
disabilities and challenged common misperceptions and stereotypes; and (4)
"disability confidence" which includes having knowledge of people with
disabilities, inclusive, and positive attitudes towards them. CONCLUSIONS:
Volunteering is one way that can help to develop disability confidence. Youth
with and without disabilities both reported a similar process of developing
disability confidence; however, there were nuances between the two groups.
Implications for Rehabilitation The development of disability confidence is
important for enhancing the social inclusion of people with disabilities.
Volunteering with people who have a disability, or a disability different from
their own, can help to develop disability confidence which involves positive
attitudes, empathy, and appropriate communication skills. Clinicians, educators,
and employers should consider promoting working with disabled people through such
avenues as volunteering or service learning to gain disability confidence.
PMID- 28503959
TI - Emerging drugs for prevention of T-cell mediated rejection in liver and kidney
transplantation.
AB - INTRODUCTION: Acute and chronic graft rejection continues to be an important
problem after solid organ transplantation. With the introduction of potent
immunosuppressive agents such as calcineurin inhibitors, the risk of rejection
has been significantly reduced. However, the adverse effects of life-long
immunosuppression remain a concern, and there exist a fine balance between over
immunosuppression and risk of rejection. Areas covered: In this review, the
current standard of care in immunosuppressive therapy, including the use of
steroids, calcineurin inhibitors, mycophenolate prodrugs and mammalian target of
rapamycin inhibitors, will be discussed. Newer immunosuppressive agents showing
promising early data after liver and kidney transplantation will also be
explored. Expert Opinion: Currently, calcineurin inhibitors continue to be a
vital component of immunosuppressive therapy after solid organ transplantation.
Although minimization and avoidance strategies have been developed, the ultimate
goal of inducing tolerance remains elusive. Newer emerging agents should have
potent and specific immunosuppressive activity, with minimal associated side
effects. An individualized approach should be adopted to tailor immunosuppression
according to the different needs of recipients.
PMID- 28503958
TI - Neonatal management and outcome in alloimmune hemolytic disease.
AB - INTRODUCTION: Hemolytic disease of the fetus and newborn (HDFN) occurs when fetal
and neonatal erythroid cells are destroyed by maternal erythrocyte
alloantibodies, it leads to anemia and hydrops in the fetus, and
hyperbilirubinemia and kernicterus in the newborn. Postnatal care consists of
intensive phototherapy and exchange transfusions to treat severe
hyperbilirubinemia and top-up transfusions to treat early and late anemia. Other
postnatal complications have been reported such as thrombocytopenia, iron
overload and cholestasis requiring specific management. Areas covered: This
review focusses on the current neonatal management and outcome of hemolytic
disease and discusses postnatal treatment options as well as literature on long
term neurodevelopmental outcome. Expert commentary: Despite major advances in
neonatal management, multiple issues have to be addressed to optimize postnatal
management and completely eradicate kernicterus. Except for strict adherence to
guidelines, improvement could be achieved by clarifying the epidemiology and
pathophysiology of HDFN. Several pharmacotherapeutic agents should be further
researched as alternative treatment options in hyperbilirubinemia, including
immunoglobulins, albumin, phenobarbital, metalloporphyrins, zinc, clofibrate and
prebiotics. Larger trials are warranted to evaluate EPO, folate and vitamin E in
neonates. Long-term follow-up studies are needed in HDFN, especially on
thrombocytopenia, iron overload and cholestasis.
PMID- 28503960
TI - Management of severe complications in Behcet's disease with TNF inhibitors.
AB - INTRODUCTION: The efficacy of anti-TNFalpha agents has been recently evaluated in
many studies in Behcet's disease (BD), particularly in ocular and life
threatening manifestations such as neurological and vascular disease. Areas
covered: The following article aims to summarize the currently available efficacy
and safety data of anti-TNFalpha agents in BD. Expert opinion: Most studies have
shown dramatic and rapid efficacy with anti-TNFalpha agents on the main BD
associated issues including posterior uveitis, gastro-intestinal and neurological
complications as well as major vessel disease. Experts in the field do recommend
the use of anti-TNF agents (either infliximab or adalimumab) as a first-line
therapy in severe posterior uveitis in BD and now use anti-TNFalpha treatment in
BD-associated life threatening manifestations. However, data is mainly based on
retrospective cohorts or open-label prospective studies. Controlled studies
(versus conventional immunosuppressants such as azathioprine and
cyclophosphamide) are warranted to properly evaluate their efficacy as first line
therapeutic in life-threatening manifestations of BD.
PMID- 28503961
TI - Psychometric properties of the neck disability index amongst patients with
chronic neck pain using item response theory.
AB - OBJECTIVE: The Neck Disability Index (NDI) is commonly used for clinical and
research assessment for chronic neck pain, yet the original version of this tool
has not undergone significant validity testing, and in particular, there has been
minimal assessment using Item Response Theory. The goal of the present study was
to investigate the psychometric properties of the original version of the NDI in
a large sample of individuals with chronic neck pain by defining its internal
consistency, construct structure and validity, and its ability to discriminate
between different degrees of functional limitation. METHODS: This is a cross
sectional cohort study of 585 consecutive patients with chronic neck pain seen in
a university hospital rehabilitation clinic. Internal consistency was evaluated
using Cronbach's alpha, construct structure was evaluated by exploratory factor
analysis, and discrimination ability was determined by Item Response Theory.
RESULTS: The NDI demonstrated good internal consistency assessed by Cronbach's
alpha (0.87). The exploratory factor analysis identified only one factor with
eigenvalue considered significant (cutoff 1.0). When analyzed by Item Response
Theory, eight out of 10 items demonstrated almost ideal difficulty parameter
estimates. In addition, eight out of 10 items showed high to perfect estimates of
discrimination ability (overall range 0.8 to 2.9). CONCLUSIONS: Amongst patients
with chronic neck pain, the NDI was found to have good internal consistency, have
unidimensional properties, and an excellent ability to distinguish patients with
different levels of perceived disability. Implications for Rehabilitation The
Neck Disability Index has good internal consistency, unidimensional properties,
and an excellent ability to distinguish patients with different levels of
perceived disability. The Neck Disability Index is recommended for use when
selecting patients for rehabilitation, setting rehabilitation goals, and
measuring the outcome of intervention.
PMID- 28503962
TI - Impact of price deregulation policy on the affordability of essential medicines
for women's health: a panel data analysis.
AB - BACKGROUND: A new policy which required deregulation on prices of off-patent
medicines for women's health during procurement was introduced in China in
September 2015. The current study examines this policy's impact on the
affordability of essential medicines for women's health. METHODS: Based on
product-level panel data, a fixed effect regression model is employed by using
procurement records from Hubei Centralist Tender for Drug Purchase platform. In
the model, Affordability was measured with prices. The Competition consists of
two parts: generic competition and therapeutic class competition which are
measured with generic competitors and therapeutic substitutes. Instrument
variable is used to deal with endogeneity. RESULTS: The policy helped control
prices of essential medicines for women's health. Generic competition helped
control prices, however, therapeutic class competition caused higher prices.
CONCLUSIONS: The new policy helped enhance the affordability of essential
medicines for women's health as expected, which provides empirical evidence on
price deregulation. Besides, generic competition is important in price control
despite strict regulatory system in China.
PMID- 28503963
TI - Nominal group technique for individuals with cognitive disability: a systematic
review.
AB - RATIONALE: Considering the perspectives of individuals with cognitive disability
is important for their participation in their self-directed health care. The
nominal group technique (NGT) has been identified as a method to gather opinions
of people with cognitive disability; however, a synthesis of methodological
considerations to undertake when employing the approach among people with
cognitive disability is non-existent. METHOD: A systematic review guided by the
preferred reporting items for systematic review and meta-analysis protocols was
undertaken. Five databases (CINAHL, ISI Web of Science, ProQuest Social Science
Journals, Scopus, and MEDLINE) were searched for peer-reviewed literature
published before September 2016. Methodological considerations pertaining to the
four stages of the NGT- generating ideas, recording ideas, clarification, and
ranking - were extracted from each study. RESULTS: Nine publications contributing
to eight studies were included. Methodological considerations focused on (i) the
number of participants within discussion groups, (ii) research question
introduction, (iii) support individuals and accessible methods, (iv) ranking, and
(v) researcher training and counselling services. CONCLUSIONS: The use of the NGT
to gain the health care perspectives of adults with cognitive disability is
promising. Conducting nominal group techniques informed by the methodological
considerations identified within this review can work towards ensuring that the
health care perspectives of people with cognitive disability are considered.
Implications for rehabilitation The emergent policy move towards self-directed
health care for people with disability requires that the health care perspectives
of people with disability are considered. Effective consultation and discussion
techniques are essential to gain the health care perspectives of people with
cognitive disability. After undertaking methodological considerations, the NGT
can be an effective approach towards gaining the health care perspectives of
people with cognitive disability.
PMID- 28503964
TI - Recent advances in intensity modulated radiotherapy and proton therapy for
esophageal cancer.
AB - INTRODUCTION: Radiotherapy is an important component of the standard of care for
esophageal cancer. In the past decades, significant improvements in the planning
and delivery of radiation techniques have led to better dose conformity to the
target volume and improved normal tissue sparing. Areas covered: This review
focuses on the advances in radiotherapy techniques and summarizes the availably
dosimetric and clinical outcomes of intensity-modulated radiation therapy (IMRT),
volumetric modulated arc therapy, proton therapy, and four-dimensional
radiotherapy for esophageal cancer, and discusses the challenges and future
development of proton therapy. Expert commentary: Although three-dimensional
conformal radiotherapy is the standard radiotherapy technique in esophageal
cancer, the retrospectively comparative studies strongly suggest that the
dosimetric advantage of IMRT over three-dimensional conformal radiotherapy can
translate into improved clinical outcomes, despite the lack of prospective
randomized evidence. As a novel form of conventional IMRT technique, volumetric
modulated arc therapy can produce equivalent or superior dosimetric quality with
significantly higher treatment efficiency in esophageal cancer. Compared with
photon therapy, proton therapy has the potential to achieve further clinical
improvement due to their physical properties; however, prospective clinical data,
long-term results, and cost-effectiveness are needed.
PMID- 28503965
TI - Prevalence of Campylobacter species in wild birds of South Korea.
AB - Campylobacter species cause human gastrointestinal infections worldwide. They
commonly inhabit intestines of avian species including wild birds. They might
play a role in the spread of infections to humans and other bird species. The
prevalence of Campylobacter species in 2164 faecal samples of wild birds
(representing 71 species and 28 families) captured across the Korean peninsula
was evaluated in this study. The overall prevalence was 15.3% (332/2164). Bird
species belonging to the family Charadriidae had the highest isolation rate
(30.0%), followed by those belonging to the families Ardeidae (26.4%), Turdidae
(21.9%), and Anatidae (15.3%). The prevalence of Campylobacter spp. differed
significantly according to migratory habit. Stopover birds were the most commonly
infected (19.0%), followed by winter migratory (16.7%) and summer migratory birds
(12.3%). However, indigenous birds showed very low prevalence (2.7%).
Antimicrobial susceptibility tests were performed for 213 isolates. Results
showed that Campylobacter jejuni isolates (n = 169) exhibited resistance to
nalidixic acid (5.3%), ciprofloxacin (3.0%), and tetracycline (1.8%), while
Campylobacter lari (n = 1) displayed resistance to nalidixic acid and
ciprofloxacin. However, all Campylobacter coli isolates (n = 20) were susceptible
to all antimicrobials tested. This is the first report on the prevalence of
Campylobacter species in wild birds that seasonally or indigenously inhabit the
Korean peninsula. Our results indicate that the overall prevalence of
Campylobacter in wild birds is moderate. Therefore, birds might serve as
significant reservoirs for Campylobacter pathogens.
PMID- 28503966
TI - Topical use of dexpanthenol: a 70th anniversary article.
AB - Approximately 70 years ago, the first topical dexpanthenol-containing formulation
(BepanthenTM Ointment) has been developed. Nowadays, various topical dexpanthenol
preparations exist, tailored according to individual requirements. Topical
dexpanthenol has emerged as frequently used formulation in the field of
dermatology and skin care. Various studies confirmed dexpanthenol's moisturizing
and skin barrier enhancing potential. It prevents skin irritation, stimulates
skin regeneration and promotes wound healing. Two main directions in the use of
topical dexpanthenol-containing formulations have therefore been pursued: as skin
moisturizer/skin barrier restorer and as facilitator of wound healing. This 70th
anniversary paper reviews studies with topical dexpanthenol in skin conditions
where it is most frequently used. Although discovered decades ago, the exact
mechanisms of action of dexpanthenol have not been fully elucidated yet. With the
adoption of new technologies, new light has been shed on dexpanthenol's mode of
action at the molecular level. It appears that dexpanthenol increases the
mobility of stratum corneum molecular components which are important for barrier
function and modulates the expression of genes important for wound healing. This
review will update readers on recent advances in this field.
PMID- 28503968
TI - The Five Stages of Prisoner Reentry: Toward a Process Theory.
AB - This article is based on an ethnographic study involving 58 Roma and Romanian
participants who were released from Jilava Prion in Romania between January and
July 2015. The methodology involved interviews, observation, questionnaires, and
photovoice. The findings seem to suggest that most of the factors associated with
desistance and reentry in the literature are relevant to the ex-prisoner's
experiences. The main contribution of this article is the observation that these
factors come into play at different times and in different stages of the reentry
process. Five reentry stages were identified in this study: prerelease
anticipation, recovery and reunion, activation, consolidation, and relapse. The
aim of the article is to describe this reentry process as the participants
experienced it. Theoretical and practice implications are discussed.
PMID- 28503967
TI - Cytotoxic and cytoprotective effects of tryptamine-4,5-dione on neuronal cells: a
double-edged sword.
AB - Serotonin (5-hydroxytryptamine) is a putative substrate for myeloperoxidase,
which may convert it into the reactive quinone tryptamine-4,5-dione (TD). In this
study, we found that the viability of human SH-SY5Y neuroblastoma cells treated
with 25 MUM TD was increased to approximately 117%. On the other hand, the cell
viability was significantly decreased by exposure to TD (150-200 MUM), with an
increase in intracellular reactive oxygen species (ROS). Interestingly, pre
treatment of SH-SY5Y cells with 100 MUM TD prevented cell death and suppressed
intracellular ROS generation evoked by the addition of hydrogen peroxide (H2O2).
Expression of the phase-II antioxidant enzyme NAD(P)H: quinone oxidoreductase 1
and haem oxygenase 1 were upregulated by TD at a concentration of 50-100 MUM.
Nuclear factor erythroid 2-related factor 2 (Nrf2), the regulator of these
enzyme, was translocated from the cytosol to the nucleus by 100 MUM TD. In
summary, moderate concentrations of TD may increase the self-defence capacity of
neuronal cells against oxidative stress.
PMID- 28503969
TI - Essential thrombocythemia: a review of the clinical features, diagnostic
challenges, and treatment modalities in the era of molecular discovery.
AB - Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm that is
associated with diminished quality of life, thrombohemorrhagic complications, and
transformation to myelofibrosis (MF) and acute leukemia (AML). The important
recent discoveries of driver mutations, including the calreticulin gene in
addition to JAK2 and MPL, have led to a greater understanding of disease
pathogenesis and set the stage for the advent of more sophisticated prognostic,
diagnostic, and therapeutic strategies. In this paper we summarize recent studies
describing the molecular basis of ET. We review the prognostic importance of
establishing a 'true' ET diagnosis, as well as risk factors for the development
of adverse outcomes including thrombosis, AML (2% risk at 15 years), and MF (9%
risk at 15 years). Finally, we discuss the decision to initiate treatment and
assess the quality of evidence supporting the use of established, available
therapies as well as novel treatments. Special situations, such as pregnancy,
familial ET, and extreme thrombocytosis will also be discussed.
PMID- 28503970
TI - Significance Test, Confidence Interval, Both or Neither?
PMID- 28503971
TI - Mental vulnerability, Helicobacter pylori, and incidence of hospital-diagnosed
peptic ulcer over 28 years in a population-based cohort.
AB - OBJECTIVE: To examine whether mental vulnerability, an enduring personality
characteristic, predicts incident hospital-diagnosed ulcer over three decades.
MATERIALS AND METHODS: A population-based cohort study enrolled 3365 subjects
with no ulcer history, ages 30-60, in 1982-3. Mental vulnerability, Helicobacter
pylori IgG antibodies, socioeconomic status, and sleep duration were determined
at baseline; non-steroidal antiinflammatory drug use, smoking, leisure time
physical activity, and alcohol consumption both at baseline and in 1993-4.
Hospital diagnoses of incident ulcer through 2011 were detected using the Danish
National Patient Registry. RESULTS: Ulcers were diagnosed in 166 subjects,
including 83 complicated by bleeding or perforation. Age-, gender-, and
socioeconomic status-adjusted associations were significant for mental
vulnerability (Hazard Ratio (HR) 2.0, 95% Confidence Interval 1.4-2.8),
Helicobacter pylori (HR 1.7, CI 1.2-2.3), smoking (HR 2.0, CI 1.3-3.1), heavy
drinking (HR 1.6, CI 1.1-2.4), abstinence (HR 1.6, CI 1.1-2.5), non-steroidal
antiinflammatory drugs (HR 2.1, CI 1.5-3.0), and sedentary lifestyle (HR 1.9, CI
1.4-2.7). Adjusted for all behavioral mediators, the HR for mental vulnerability
was 1.5 (CI 1.0-2.2, p = .04). Mental vulnerability raised risk in Helicobacter
pylori seropositive subjects and those exposed to neither Helicobacter pylori nor
non-steroidal antiinflammatory drugs; its impact was virtually unchanged when
analysis was limited to complicated ulcers. CONCLUSIONS: A vulnerable personality
raises risk for hospital-diagnosed peptic ulcer, in part because of an
association with health risk behaviors. Its impact is seen in 'idiopathic' and
Helicobacter pylori-associated ulcers, and in acute surgical cases.
PMID- 28503972
TI - Molecular mechanisms of anti-oxidant and anti-aging effects induced by
convallatoxin in Caenorhabditis elegans.
AB - Convallatoxin is widely used as a cardiac glycoside in acute and chronic
congestive heart-failure and paroxysmal tachycardia, with many effects and
underlying protective mechanisms on inflammation and cellular proliferation.
However, convallatoxin has not been investigated in its antioxidant effects and
lifespan extension in Caenorhabditis elegans. In this study, we found that
convallatoxin (20 MUM) could significantly prolong the lifespan of wild-type C.
elegans up to 16.3% through daf-16, but not sir-2.1 signalling and increased
thermotolerance and resistance to paraquat-induced oxidative stress.
Convallatoxin also improved pharyngeal pumping, locomotion, reduced lipofuscin
accumulation and reactive oxygen species levels in C. elegans, which were
attributed to hormesis, free radical-scavenging effects in vivo, and up
regulation of stress resistance-related proteins, such as SOD-3 and HSP-16.1.
Furthermore, aging-associated genes daf-16, sod-3, and ctl-2 also appeared to
contribute to the stress-resistance effect of convallatoxin. In summary, this
study demonstrates that convallatoxin can protect against heat and oxidative
stress and extend the lifespan of C. elegans, pointing it as a potential novel
drug for retarding the aging process in humans.
PMID- 28503973
TI - Metformin use in diabetics with diverticular disease is associated with reduced
incidence of diverticulitis.
AB - BACKGROUND AND AIMS: There is no current, evidence-based therapy to prevent acute
diverticulitis in patients with diverticular disease. Metformin has been shown to
have anti-inflammatory effects in a number of disease states, in both animal
models and in human observational studies. The potential therapeutic efficacy of
metformin in diverticular disease has not been investigated. This study aims to
describe the relationship between metformin use and diverticular disease in
patients with diabetes mellitus. METHODS: This was a retrospective case-control
study. It compared metformin and other hypoglycaemic medication use in diabetic
patients with uncomplicated diverticulosis to those with acute diverticulitis.
Patients were identified using hospital International Classification of Diseases
10 (ICD-10) data, and radiology, pathology and scanned medical record databases
were used to confirm diagnoses and collect all information. Chi square tests were
used to determine significance of difference in categorical variables, and Mann
Whitney tests were used for continuous data. RESULTS: There were 174 patients
with uncomplicated diverticulosis and 175 patients with acute diverticulitis. A
diagnosis of acute diverticulitis was associated with a significantly lower
incidence of metformin use, than a diagnosis of uncomplicated diverticular
disease (44% compared to 60%, respectively, p = .002). Other oral hypoglycaemic
drugs and insulin were not associated with a lower incidence of diverticulitis (p
= .12 and p = .24, respectively). CONCLUSION: Metformin use is associated with
reduced incidence of diverticulitis in diabetic patients with diverticular
disease. The utility of metformin as a therapeutic agent to reduce the risk of
diverticulitis in patients with diverticular disease warrants further randomised,
prospective, interventional investigation.
PMID- 28503974
TI - Biokinetics of engineered nano-TiO2 in rats administered by different exposure
routes: implications for human health.
PMID- 28503975
TI - Body image after heart transplantation compared to mechanical aortic valve
insertion.
AB - OBJECTIVE: Heart transplantation (HT) obviously affects body image and integrity.
However, there are very few empirical data post-transplant. METHODS: In a cross
sectional study, 57 HT patients were compared with 47 subjects with mechanical
aortic valve replacement (AVR) using the Dresden-Body-Image questionnaire (DKB)
and specific questions regarding integration of the organ/device. In addition,
affective symptoms and quality of life (QoL) were assessed (12-Item Short-Form
Health Survey and Hospital Anxiety and Depression Scale, HADS). RESULTS: DKB-35
scores did not differ. HT patients scored higher than AVR on specific questions
regarding integration of the organ/device. AVR patients showed more affective
disturbance and lower mental QoL than HT subjects. Affective scores correlated
negatively with body image scores. Seventeen percent of all patients showed
psychological distress (HADS scores >8). CONCLUSIONS: HT patients integrated the
new organ well - and even better than AVR subjects did with the device. In
general, our data corroborate a good adaptation process, in particular in HT
patients. Similar to other reported data, a subgroup of 15-20% of patients shows
stronger mental distress, including body image problems. These must be identified
and treated by professionals. Patients with AVR deserve more attention in the
future.
PMID- 28503976
TI - Self-extubation Laryngeal Injuries at an Academic Tertiary Care Center: A
Retrospective Pilot Study.
AB - OBJECTIVES: The purpose of this study is to identify laryngeal symptoms and
injuries in self-extubated patients. METHODS: A retrospective chart review was
conducted to identify symptoms and clinical findings associated with self
extubation. A novel scoring system was developed and used to quantify these
findings. Symptom score included all symptoms that patients reported after self
extubation. Clinical score consisted of laryngeal findings visualized on
nasopharyngeal laryngoscopy. Finally, a total self-extubation score was
calculated as the sum of the symptom and clinical scores. Additionally, duration
of intubation and endotracheal tube size were correlated with these scores.
RESULTS: Sixty (n = 60) patients who self-extubated in our institution's
intensive care unit were identified. Average calculated symptom, clinical, and
total self-extubation scores were 0.92, 1.43, and 2.35, respectively. The most
common symptom observed was hoarseness (62%), while the most common clinical
finding was posterior laryngeal edema (58%). A significant positive correlation
was found between duration of intubation and both symptom score and total self
extubation score (r = 0.314, P = .008 and r = 0.223, P = .05, respectively).
Symptom score predicted clinical score with a significant positive correlation
present (r = 0.278, P = .02). CONCLUSIONS: This study demonstrates that the
majority of self-extubated patients have laryngeal symptoms and clinical
findings. A comprehensive, multidisciplinary evaluation is warranted for self
extubations.
PMID- 28503978
TI - Comparison of depression symptoms between primary depression and secondary-to
schizophrenia depression.
AB - OBJECTIVES: This study exclusively aimed to clinically assess which symptom
pattern discriminates primary depression from depression-secondary to
schizophrenia. METHODS: A total of 98 patients with primary depression and 71
patients with secondary-to-schizophrenia depression were assessed for identifying
the clinical phenomena of depression. Diagnosis of schizophrenia was confirmed by
Mini International Neuropsychiatric Interview. Each participant was, however,
assessed by Patient Health Questionnaire-9 as well as Calgary Depression Scale
for Schizophrenia (CDSS) for possible concurrent depressive symptoms. RESULTS:
Depressed mood, loss of interest, reduced energy and pathological guilt were more
common in primary depression, whereas sleep disturbance and guilty ideas of
reference were more amounting towards the diagnosis of depression secondary-to
schizophrenia. CONCLUSIONS: It is clinically hard to differentiate primary from
secondary-to-schizophrenia depression, especially in the absence of obvious
psychotic symptoms. However, the classical symptoms of depression like subjective
depressed mood, anhedonia, reduced energy and pathological guilt are more
prominent in the primary depression.
PMID- 28503977
TI - Emerging treatments for ulcerative colitis: a systematic review.
AB - OBJECTIVES: Various investigational medicinal products have been developed for
ulcerative colitis (UC). Our aim was to systematically evaluate novel
pharmacological therapeutic agents for the treatment of UC. MATERIAL AND METHODS:
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
recommendations were followed. A search of the medical literature was conducted
in the MEDLINE database for original research papers published between 01 January
2010 and 31 October 2014. RESULTS: Twenty one studies, including 11,524 adults
were analyzed. Thirteen different novel therapeutic drug options were identified.
Vedolizumab and golimumab were superior to placebo as induction and maintenance
therapy. Tofacitinib showed dose related efficacy for induction therapy.
Etrolizumab showed higher clinical remission rates compared to placebo.
Phosphatidylcholine led to an improved clinical activity index. HMPL-004 may
become a mesalamine alternative for mild to moderate UC. PF00547,659 was well
tolerated. Statins were not beneficial for acute exacerbations of UC. Abatacept,
rituximab and visilizumab did not lead to improved outcomes compared to placebo.
Higher concentration of BMS 936557 was associated with improved efficacy compared
to placebo. Basiliximab did not enhance corticosteroid efficacy. CONCLUSIONS:
Patients with UC might achieve clinical response or remission by utilizing some
of these agents with a favorable side effect profile. Further studies are needed
to evaluate their short- and long-term efficacy and safety.
PMID- 28503979
TI - Expression of the IFNAR1 chain of type 1 interferon receptor in benign cells
protects against progression of acute leukemia.
AB - Type I interferons (IFN) were widely used for leukemia treatment. These cytokines
act on cell surface receptor consisting of the IFNAR1/2 chains to induce anti
tumorigenic effects. Given that levels of IFNAR1 can be regulated by
phosphorylation-driven ubiquitination and degradation that undermines IFN
signaling and anti-tumorigenic effects, we sought to determine the importance of
IFNAR1 downregulation in progression of acute leukemia. Using knock-in mice
deficient in downregulation of IFNAR1, we uncovered that IFNAR1 expression in
stromal benign cells functions to protect against progression of leukemia. We
discuss putative mechanisms of this regulation and potential of therapeutic
targeting of IFNAR1 downregulation to treat leukemia.
PMID- 28503980
TI - Assessment of oxidative stress induced by gold nanorods following intra-tracheal
instillation in rats.
AB - Gold nanorods (GNRs) are used for their wide variety of applications in various
industries. There is a little availability of data related to toxicity and
ecological implications of these GNRs. The study evaluated the oxidative stress
induction following intra-tracheal instillation of 1 and 5 mg/kg b.w. doses of 10
and 25 nm GNRs by estimating various oxidative stress markers including lipid
peroxidation (malondialdehyde; MDA), glutathione (GSH), superoxide dismutase
(SOD), catalase and total antioxidant capacity (TAC) after 1 day, 1 week, 1
month, and 3 months post exposure periods. The results have shown increased MDA
levels and decreased GSH levels following 1 day and 1 week post exposure periods,
indicating induction of oxidative stress. Also, the SOD, catalase and TAC levels
were significantly decreased following exposure of both 10 and 25 nm GNRs after 1
day and 1 week after exposures, indicating the inhibition of antioxidant defense
mechanisms. Moreover, the 10 nm GNRs at 5 mg/kg dose displayed greater changes in
all the estimated parameters, representing dose and size based induction of
oxidative stress by GNRs. In contrast, a little change was observed during 1
month and 3 months post exposure periods, may be due to recovery. Finally, the
GNRs induced dose-size-dependent oxidative stress induction by various oxidative
stress markers following intra-tracheal instillation in rats.
PMID- 28503981
TI - Platelet reactivity influences clot structure as assessed by fractal analysis of
viscoelastic properties.
AB - Despite the interwoven nature of platelet activation and the coagulation system
in thrombosis, few studies relate both analysis of protein and cellular parts of
coagulation in the same population. In the present study, we use matched ex vivo
samples to determine the influences of standard antiplatelet therapies on
platelet function and use advanced rheological analyses to assess clot formation.
Healthy volunteers were recruited following fully informed consent then treated
for 7 days with single antiplatelet therapy of aspirin (75 mg) or prasugrel (10
mg) or with dual antiplatelet therapy (DAPT) using aspirin (75 mg) plus prasugrel
(10 mg) or aspirin (75 mg) plus ticagrelor (90 mg). Blood samples were taken at
day 0 before treatment and at day 7 following treatment. We found that aspirin
plus prasugrel or aspirin plus ticagrelor inhibited platelet responses to
multiple agonists and reduced P-selectin expression. Significant platelet
inhibition was coupled with a reduction in fractal dimension corresponding to
reductions in mean relative mass both for aspirin plus prasugrel (-35 +/- 16%
change, p = 0.04) and for aspirin plus ticagrelor (-45 +/- 14% change, p = 0.04).
Aspirin alone had no effect upon measures of clot structure, whereas prasugrel
reduced fractal dimension and mean relative mass. These data demonstrate that
platelets are important determinants of clot structure as assessed by fractal
dimension (df) and that effective platelet inhibition is associated with a
weaker, more permeable fibrin network. This indicates a strong association
between the therapeutic benefits of antiplatelet therapies and their abilities to
reduce thrombus density that may be useful in individual patients to determine
the functional relationship between platelet reactivity, eventual clot quality,
and clinical outcome. df could represent a novel risk stratification biomarker
useful in individualizing antiplatelet therapies.
PMID- 28503983
TI - Design and in vitro evaluation of tenofovir-loaded vaginal gels for the
prevention of HIV infections.
AB - Infection with the human immunodeficiency virus (HIV) is affecting women
disproportionally with increasing incidence rates over the last decades.
Tenofovir is one of the most commonly used antiretroviral agents, which belongs
to the nucleoside/nucleotide reverse transcriptase inhibitor family, for the
prevention of HIV acquisition. In scope of this study, a thermogelling system
containing tenofovir-loaded chitosan nanoparticles for the controlled release of
tenofovir was developed and characterized. The in vitro release studies have
shown that the burst release effect was decreased to 27% with f-TFV CS NPs-Gel.
Gelation temperature of developed formulation was found as 26.6 +/- 0.2 degrees
C, which provides ease of administration while gelation occurs after the
administration to the vagina. The work of adhesion values was used as parameters
for comparison of mucoadhesive performance and the mucoadhesion of f-TFV CS NPs
Gel was found as 0.516 +/- 0.136 N.s at 37 degrees C. The biocompatibility of
blank formulations was evaluated by cell viability studies using L929 cells, in
which Gel + CS NPs formulation was found to be safe with 82.4% and 90.2% cell
viability for 1:16 and 1:32 dilutions, respectively. In conclusion, an improved
tenofovir containing vaginal gel formulation was successfully developed and
evaluated for preventing HIV transmission.
PMID- 28503982
TI - Anxiety and depression affect pain drawings in cervical degenerative disc
disease.
AB - INTRODUCTION: Pain drawings have been frequently used in the preoperative
evaluation of spine patients. Until now most investigations have focused on low
back pain patients, even though pain drawings are used in neck pain patients as
well. The aims of this study were to investigate the pain drawing and its
association to preoperative demographics, psychological impairment, and pain
intensity. METHODS: We carried out a post hoc analysis of a randomized controlled
trial, comparing cervical disc replacement to fusion for radiculopathy related to
degenerative disc disease. Preoperatively the patients completed a pain drawing,
the Hospital Anxiety and Depression Scale (HADS), and a visual analogue scale
(VAS). The pain drawing was evaluated according to four established methods, now
modified for cervical conditions. Comparisons were made between the pain drawing
and age, sex, smoking, and employment status as well as HADS and VAS. RESULTS:
Included were 151 patients, mean age of 47 years, female/male: 78/73. Pain
drawing results were not affected by age, sex, smoking, and employment status.
Patients with non-neurogenic pain drawings according to the modified method by
Ransford had higher points on HADS-anxiety, HADS-depression, and HADS-total.
Patients with markings in the head region had higher score on HADS-depression.
Markings in the neck and lower arm region were associated with high values of VAS
neck and VAS-arm. CONCLUSIONS: Pain drawings were affected by both pain intensity
and anxiety/depression in cervical spine patients. Therefore, the pain drawing
can be a useful tool when interpreting the patients' pain in correlation to
psychological impairment and pain location.
PMID- 28503984
TI - The genotoxic effect of oxcarbazepine on mice blood lymphocytes.
AB - This study was conducted to assess the amount of DNA damage caused by
Oxcarbazepine (OXC) through single cell gel electrophoresis (SCGE)
technique/comet assay. OXC derived from dibenzazepine series is an effective
second generation antiepileptic drug (AED) for both children and adults. Side
effects like genotoxic effects of AEDs are of prime importance resulting from
toxic metabolites, free radicals and reactive oxygen species (ROS). Forty Eight
adult male Bagg's albino mice (BALB/c) were randomly classified into eight
groups, each comprising of six animals. Two of these groups were control and six
were tested groups. Control groups were injected with 1% tween 80 while tested
groups were injected with 10, 20, and 40 mg/kg-day OXC for seven days (acute
therapy) and 28 days (subchronic therapy) in peritoneal cavity. Blood samples
were collected by cardiac puncture and subjected to comet assay for the analysis
of DNA damage. Per sample 100 cells were scored and classified according to comet
tail length. The results showed that OXC in acute and long term therapies had
significantly higher (p < 0.05) genotoxicity in treated groups as compared to
control groups. Our study suggests that OXC may cause significant DNA damage in
both acute as well as in subchronic therapies.
PMID- 28503985
TI - Diagnostic and Therapeutic Management of a First Unprovoked Seizure in Children
and Adolescents With a Focus on the Revised Diagnostic Criteria for Epilepsy.
AB - By definition, unprovoked seizures are not precipitated by an identifiable
factor, such as fever or trauma. A thorough history and physical examination are
essential to caring for pediatric patients with a potential first unprovoked
seizure. Differential diagnosis, EEG, neuroimaging, laboratory tests, and
initiation of treatment will be reviewed. Treatment is typically initiated after
2 unprovoked seizures, or after 1 seizure in select patients with distinct
epilepsy syndromes. Recent expansion of the definition of epilepsy by the ILAE
allows for the diagnosis of epilepsy to be made after the first seizure if the
clinical presentation and supporting diagnostic studies suggest a greater than
60% chance of a second seizure. This review summarizes the current literature on
the diagnostic and therapeutic management of first unprovoked seizure in children
and adolescents while taking into consideration the revised diagnostic criteria
of epilepsy.
PMID- 28503986
TI - Minority stress model components and affective well-being in a sample of sexual
orientation minority adults living with HIV/AIDS.
AB - To date very little literature exists examining theoretically-based models
applied to day-to-day positive and negative affective well-being among lesbian,
gay, and bisexual (LGB) persons living with HIV/AIDS (PLWHA). Grounded in the
perspective of Meyer, I. H. (2003). Prejudice, social stress, and mental health
in lesbian, gay, and bisexual populations: Conceptual issues and research
evidence. Psychological Bulletin, 129, 674-697. Minority Stress Model, the
present study examined HIV- and sexual orientation-related factors influencing
affective well-being (i.e., positive affect, negative affect, life satisfaction,
and stress). Participants were 154 HIV-positive LGB adults from an urban area in
the southwestern United States. Data were drawn from an archival database (i.e.,
Project Legacy). The study methodology featured a cross-sectional self-report
survey of minority stress, victimization, coping, and emotional well-being, among
other subjects. Primary regression results were: (1) males reported less general
stress than females; (2) higher internalized HIV-related stigma was associated
with elevated negative affect; (3) higher internalized homophobia was associated
with elevations in negative affect and general stress; (4) higher coping self
efficacy was associated with lesser negative affect, lesser general stress,
greater positive affect, and greater satisfaction with life; (5) a significant
interaction between HIV-related victimization and coping self-efficacy showed
that coping self-efficacy was positively associated with positive affect only
(only for non-victims). Contrary to expectations, coping self-efficacy
demonstrated the largest main effects on affective well-being. Results are
discussed with regard to potential need for theoretical refinement of Minority
Stress Model applied to PLWHA and affective well-being outcomes. Recommendations
are offered for future research.
PMID- 28503987
TI - Prevalence of chronic kidney disease and its determinants in coronary heart
disease patients in 24 European countries: Insights from the EUROASPIRE IV survey
of the European Society of Cardiology.
AB - Aims Chronic kidney disease (CKD) is associated with the development and
progression of coronary heart disease (CHD), in addition to classic
cardiovascular risk factors. We analysed the prevalence of CKD in CHD patients
from 24 European countries in the ambulatory setting and in a preceding hospital
stay for CHD (index). Methods and results A total of 7998 EUROASPIRE IV
participants (median 65 years of age, 76% male) attended a study visit 6-36
months after the index hospitalisation. CKD was classified according to stages of
estimated glomerular filtration rate (eGFR) and albuminuria (urinary
albumin/creatinine ratio). In stable CHD conditions (study visit), 17.3% had CKD
(eGFR <60 mL/min/1.73 m2) with variation among participating countries (range
13.1-26.4%). A further 12% presented with preserved eGFR but significant
albuminuria. During the hospital stay due to a coronary event, impaired kidney
function was observed in 17.6% (range 7.5-38.2%). Risk factors for impaired
kidney function included older age, female gender, classic cardiovascular (CV)
risk factors, details of CHD history and congestive heart failure (multivariate
regression). Of all patients, 38.9% had declined, 31.3% were stable and 29.8% had
improved kidney function between hospital discharge and the study visit,
dependent on age, gender, CV risk factors, CHD history and cardiac dysfunction
(multivariate regression). Conclusions Every fifth CHD patient had CKD, while
every tenth exhibited albuminuria as the sole indicator of kidney damage. These
subjects are at increased risk of progression of CKD and CHD complications. After
hospital stays due to CHD, there is potential of recovery of kidney function, but
our findings underline the importance of identifying patients who are at high
risk of developing CKD in order to counteract disease progression.
PMID- 28503988
TI - The usefulness of narrow-band imaging for the diagnosis and treatment of vocal
fold leukoplakia.
AB - OBJECTIVE: This research was aimed to explore the efficacy of narrow-band imaging
(NBI) on distinguishing the degree of dysplasia of vocal fold leukoplakia.
METHODS: Patients were examined by flexible endoscopy, under white light
endoscopy (WLE) and NBI. 78 lesions were divided into two groups according to the
NBI classification. Group 1: non-dysplasia (ND), including squamous hyperplasia
with hyperkeratosis or parakeratosis; Group 2: squamous hyperplasia with mild or
moderate dysplasia (MD) or severe dysplasia (SD), or carcinoma in situ (CIS).
RESULTS: The diagnostic accuracy of NBI for Group 1 and Group 2 was 69.70%
(23/33) and 95.56% (43/45), respectively, and the kappa index was 0.711 and a p
value < .05, which was considered statistically significant. CONCLUSIONS: The NBI
could roughly estimate the degree of dysplasia. Differentiating between ND, MD,
SD, and CIS, which may be useful for clinicians on selecting suitable therapies.
PMID- 28503989
TI - Intravenous olfactory test latency correlates with improvement in post-infectious
olfactory dysfunction.
AB - CONCLUSION: This cohort study showed that onset latency in the intravenous
olfactory test (IVO) may help predict when olfaction in patients with post
infectious olfactory dysfunction (PIOD) improves. OBJECTIVES: To identify factors
that predict the olfactory improvement period in patients with PIOD.
METHODOLOGY/PRINCIPAL: All consecutive patients presenting with PIOD in 1994-2014
who were followed up for 2 years were identified retrospectively. The ability of
demographic/clinical factors (age, sex, body mass index, presence/absence of
allergic rhinitis, treatment/non-treatment with herbal medicines, patient
dependence on herbal medicine treatment, presence/absence of diabetes mellitus,
and smoking status) and olfactory test factors (response/no response and onset
latency and duration in the IVO test, and detection and recognition scores on the
T&T olfactory test) to predict the olfactory improvement period (defined
respectively as the time from PIOD onset or olfactory testing to the first self
report of olfaction improvement) was analyzed by univariate and multivariate
regression. RESULTS: Of the 187 PIOD patients, the prognostic ability of
demographic/clinical factors was analyzed in 65. None predicted the olfactory
improvement period. Of the 65 patients, 20 did not respond in the IVO test. In
the remaining 45 patients, onset latency (but not the other olfactory test
factors) was a significant prognosticator of olfactory improvement period
(R2=0.24, p = 0.003).
PMID- 28503990
TI - Assessing the utilization of radiotherapy near end of life at a Finnish
University Hospital: a retrospective cohort study.
AB - BACKGROUND: Palliative radiotherapy can improve quality of life for cancer
patients during the last months of life. However, very short life expectancy may
devastate the benefit of the treatment. This single center study assesses the
utilization of radiotherapy during the last weeks of life. MATERIAL AND METHODS:
All cancer patients (N = 38,982) treated with radiotherapy (N = 11,395) in Turku
University Central Hospital during 2005-2013 were identified in the database
consisting of electronic patient records. One fourth (N = 2904, 25.5%) of the
radiotherapy treatments were given during the last year of life. The last
radiotherapy treatments and the time from the last radiotherapy treatment to
death were assessed in regards to patients' age, cancer diagnosis, domicile,
place of death and the treatment year. Treatments given during the last two weeks
of life were also assessed regarding the goal of treatment and the reason for
possible discontinuation. RESULTS: The median time from the last fraction of
radiotherapy to death was 84 d. During the last two weeks before death (N = 340),
pain (29.4%) was the most common indication for radiotherapy. Treatment was
discontinued in 40.6% of the patients during the last two weeks of life, and
worsening of general condition was the most common reason for discontinuity
(70.3%). The patients receiving radiotherapy during the last weeks of life were
more likely to die in tertiary care unit. During the last year of life single
fraction treatment was used only in 7% of all therapy courses. There was a
statistically significant (p < .05) decrease in the median number of fractions in
the last radiotherapy treatment between 2005-2007 (8 fractions) and 2011-2013 (6
fractions). CONCLUSIONS: Up to 70% of the treatments during the last two weeks of
life were not delivered to alleviate pain and utilization of single fraction
radiotherapy during the last year of life was infrequent. These observations
suggest that practice of radiotherapy during the last weeks of life should be
revisited.
PMID- 28503991
TI - Platelet concentrates modulate myeloid dendritic cell immune responses.
AB - Platelet transfusion has been reported to modulate the recipients' immune system.
To date, the precise mechanism(s) driving poor patient outcomes (e.g., increased
rate of mortality, morbidity, infectious complications and prolonged hospital
stays) following platelet transfusion are largely undefined. To determine the
potential for platelet concentrates (PC) to modulate responses of crucial immune
regulatory cells, a human in vitro whole blood model of transfusion was
established. Maturation and activation of human myeloid dendritic cells (mDC) and
the specialized subset blood DC antigen (BDCA)3+ DC were assessed following
exposure to buffy-coat derived PC at day (D)2 (fresh) and D5 (date-of-expiry). In
parallel, to model recipients with underlying viral or bacterial infection,
polyinosinic:polycytidylic acid or lipopolysaccharide was added. Exposure to PC
had less of an impact on mDC responses than BDCA3+ DC responses. PC alone
downregulated BDCA3+ DC expression of co-stimulatory molecules CD40 and CD80. In
the model of viral infection, PC downregulated expression of CD83, and in the
bacterial model of infection, PC downregulated CD80, CD83, and CD86. PC alone
suppressed mDC production of interleukin (IL)-8, IL-12 and tumor necrosis factor
(TNF)-alpha and BDCA3+ DC production of IL-8, IL-12, and IL-6. In the model of
viral infection, production of IL-12 and interferon-gamma inducible protein (IP)
10 was reduced in both DC subsets, and IL-8 was reduced in BDCA3+ DC following PC
exposure. When modeling bacterial infection, PC suppressed mDC and BDCA3+ DC
production of IL-6 and IL-10 with a reduction in TNF-alpha evident in mDC. This
study assessed the impact of PC "transfusion" on DC surface antigen expression
and inflammatory mediator production and provided the first evidence that PC
transfusion modulates blood mDC and BDCA3+ DC maturation and activation,
particularly in the models of infection. Results of this study suggest that
patients who receive PC, particularly those with underlying infectious
complications, may fail to establish an appropriate immune response precipitating
poor patient outcomes.
PMID- 28503992
TI - Dose-dependent effects of ouabain on spiral ganglion neurons and Schwann cells in
mouse cochlea.
AB - OBJECTIVE: This study aimed in fully investigating the toxicities of ouabain to
mouse cochlea and the related cellular environment, and providing an optimal
animal model system for cell transplantation in the treatment of auditory
neuropathy (AN) and sensorineural hearing loss (SNHL). METHODS: Different dosages
of ouabain were applied to mouse round window. The auditory brainstem responses
and distortion product otoacoustic emissions were used to evaluate the cochlear
function. The immunohistochemical staining and cochlea surface preparation were
performed to detect the spiral ganglion neurons (SGNs), Schwann cells and hair
cells. RESULTS: Ouabain at the dosages of 0.5 mM, 1 mM and 3 mM selectively and
permanently destroyed SGNs and their functions, while leaving the hair cells
relatively intact. Ouabain at 3 mM resulted in the most severe SGNs loss and
induced significant loss of Schwann cells started as early as 7 days and with
further damages at 14 and 30 days after ouabain exposure. CONCLUSIONS: The
application of ouabain to mouse round window induces damages of SGNs and Schwann
cells in a dose- and time-dependent manner, this study established a reliable and
accurate animal model system of AN and SNHL.
PMID- 28503993
TI - Dual inhibition of PI3K and mTOR by VS-5584 suppresses thrombus formation.
AB - VS-5584 is a highly selective dual kinase inhibitor which suppresses
phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR)
activity. Because these kinases are crucially involved in primary hemostasis, we
herein investigated the effect of this compound on thrombus formation in vitro
and in vivo. Pretreatment of washed platelets (WP) or platelet-rich plasma (PRP)
with VS-5584 inhibited the agonist-induced activation of surface glycoprotein
complex (GP)IIb/IIIa and the upregulation of P-selectin. This was associated with
a significantly reduced formation of platelet-leukocyte aggregates (PLA). VS-5584
further attenuated platelet aggregation and adhesion after agonist stimulation.
In contrast, endothelial expression of intercellular adhesion molecule (ICAM)-1
and vascular cellular adhesion molecule (VCAM)-1 and secretion of von Willebrand
Factor (vWF) were not affected by the dual kinase inhibitor. In vivo, VS-5584
inhibited photochemically induced thrombus formation as shown by a significantly
prolonged time to complete vessel occlusion when compared to vehicle-treated
controls. This was associated with an elevated tail vein bleeding time,
indicating a potential hemorrhagic risk in VS-5584-treated mice. Taken together,
these novel findings demonstrate that VS-5584 is a potent inhibitor of primary
hemostasis targeting multiple platelet functions.
PMID- 28503994
TI - Anti-pseudomonal and anti-endotoxic effects of surfactin-stabilized biogenic
silver nanocubes ameliorated wound repair in streptozotocin-induced diabetic
mice.
AB - Pseudomonas aeruginosa and its lipopolysaccharides play a key role in the
pathogenesis of diabetic foot infection, for which, currently no effective
therapeutic agents are available. Hence, newer forms of therapeutic agents are
required for treating Pseudomonas aeruginosa infection. In this present study,
nanocrystalline silver nanoparticles (AgNPs) were synthesized using culture
filtrate of Brevibacillus brevis KN8(2) followed by an investigation of its in
vivo anti-pseudomonal and anti-endotoxic properties. Biosynthesized AgNPs was
predominantly cubical in shape with an average particle size of 15.40 nm as
observed through field emission scanning electron microscopy (FESEM) and X-ray
diffraction analysis. The LC-ESI-MS/MS analysis indicates the presence of
surfactin in culture filtrate of B. brevis KN8(2). The MIC of surfactin
stabilized AgNPs against P. aeruginosa was 10 MUg ml-1 and its wound repair
activity was observed in P. aeruginosa-infected wounds of diabetic mice by
measuring wound area closure, bacterial counts, mRNA expressions, and
histopathology. Further, surfactin-stabilized AgNPs suppressed the transcription
of LPS-triggered expression of the TNF-alpha in wounds that LPS-assisted
extension of wound repair in diabetes mellitus conditions was circumvented quite
well. Results gathered in this study established that surfactin-stabilized AgNPs
could effectively offer to the novel treatment of Gram-negative bacilli infection
in diabetic wounds.
PMID- 28503995
TI - Preparation and characterization of surface-modified PLGA-polymeric nanoparticles
used to target treatment of intestinal cancer.
AB - Docetaxel (DTX), a cytotoxic taxane, is a poor water-soluble drug and exhibits
less oral bioavailability. Current research investigates the effective transport,
for DTX-loaded chitosan (CS)-coated-poly-lactide-co-glycolide (PLGA)
nanoparticles (NPs) (DTX-CS-PLGA-NPs) and DTX-PLGA-NPs as well as a novel third
generation P-gp inhibitor i.e. GF120918 (Elacridar), across intestinal epithelium
with its successive uptake by the tumour cells in an in vitro model. The prepared
NPs showed a spherical shape particle size i.e. <123.96 nm with polydispersity
index (PDI) of <0.290 whereas for CS-coated NPs, the zeta potential was converted
from negative to positive value along with a small modification in particle size
distribution. The entrapment efficiency observed for DTX-CS-PLGA-NPs was 74.77%,
whereas the in vitro release profile revealed an initial rapid DTX release
followed by a sustained release pattern. For apparent permeability, DTX-CS-PLGA
NPs and DTX-PLGA-NPs along with GF120918 showed a five-fold (p < .01) and 2.2
fold enhancement, respectively, as observed in rat ileum permeation study.
Similarly, for pharmacokinetic (PK) studies, higher oral bioavailability was
observed from DTX-CS-PLGA-NPs (5.11-folds) and DTX-PLGA-NPs (3.29-folds) as
compared with DTX-suspension (DTX-S). Cell uptake studies on A549 cells as
performed for DTX-CS-PLGA-NPs and DTX-PLGA-NPs loaded with rhodamine 123 dye,
exhibited enhanced uptake as compared with plain dye solution. The enhanced
uptake for DTX-CS-PLGA-NPs and DTX-PLGA-NPs formulations in the presence of
GF120918 was confirmed further with the help of confocal laser scanning
microscopic images (CLSM). The potential of the third-generation novel P-gp
inhibitor (GF120918) investigated for the effective delivery of DTX as well as
investigation of permeability and uptake studies whereby a strong potential of
GF120918 for effective oral delivery was established.
PMID- 28503996
TI - Primary Immunization of Human Papillomavirus Vaccine in the Pediatric Population:
What Is the Verdict Now?
AB - The safety and efficacy of a 2-dose series for the human papillomavirus vaccines
rather than a 3-dose series in older children has not been well defined. This
article reviews the literature summarizing the use of all 3 HPV vaccines (2vHPV,
4vHPV, 9vHPV) as a 2-dose series for females and 4vHPV and 9vHPV for males
younger than 15 years. Six prospective trials evaluating immunogenicity of a 2
dose series of 2vHPV and/or 4vHPV, as well as an ongoing prospective clinical
trial for 9vHPV, are discussed. The 2-dose series with Gardasil 9(r) in both
males and females ages 9 to 14 years appears to be the most widely accepted
recommendation. The exact time schedule between the 2 vaccines varies among
studies, but it seems that they should be separated by 6 to 12 months. Federal
and world-wide organizations' (ie, Centers for Disease Control and Prevention,
Food and Drug Administration, and World Health Organization) opinions and
recommendations on the appropriate scheduling of the vaccines are also
highlighted.
PMID- 28503997
TI - Television During Meals in the First 4 Years of Life.
AB - The development of children's mealtime television (TV) habits has not been well
studied. We assessed whether mealtime TV habits established in infancy will
persist into early childhood. We analyzed data collected through parent surveys
at birth and at 6-month intervals from a randomized controlled trial. We used t
tests, chi2 tests, and a multivariable logistic regression to determine if family
characteristics were associated with mealtime TV. A McNemar test was used to
assess whether mealtime TV exposure changed over time. College-educated fathers
and families with an annual income >$50 000 were associated with less-frequent TV
exposure during children's mealtimes. It was found that 84% of children retained
their level of exposure to TV during mealtimes from the first 24 months through
48 months of life. Clinicians should counsel families about mealtime TV use
within the first 2 years of life because these habits seem to develop early and
persist into at least early childhood.
PMID- 28503998
TI - Reducing Errors in an Emergency Center Setting Using an Automated Fluorescence
Immunoassay for Group A Streptococcus Identification.
PMID- 28504000
TI - Factors associated with successful decannulation in pediatric tracheostomy
patients.
AB - OBJECTIVES: To investigate the outcome of pediatric tracheostomy and identify
predictive factors for successful decannulation. METHODS: We performed a
retrospective chart review of a series of 42 consecutive patients of less than 24
months of age who underwent a tracheostomy between 2012 and 2015. RESULTS:
Successful decannulation was achieved in 11 patients (26%). Thirty-one patients
(74%) remained tracheostomy-dependent. Of the 11 patients who were successfully
decannulated, 10 (91%) had only structural disorders and nine (82%) were able to
walk unassisted; importantly, nine (82%) were able to swallow following
decannulation. In contrast, of the 31 patients who did not tolerate
decannulation, 21 (68%) had functional disorders and 18 (58%) were unable to walk
unassisted; 20 (65%) of the tracheostomy-dependent patients were unable to
swallow after undergoing surgery. CONCLUSION: Following pediatric tracheostomy
procedures, patients with solely structural disorders were significantly more
likely to be successfully decannulated compared to patients with functional
disorders. Furthermore, the capacity to walk unassisted and swallow after surgery
is associated with positive outcomes for decannulation. Our results suggest that
an objective evaluation of the ability to walk unassisted, and to ingest food,
may be useful for predicting the outcome and effects of tracheostomy procedures
and decannulation in children.
PMID- 28503999
TI - Quantitative assessment of brain glucose metabolic rates using in vivo deuterium
magnetic resonance spectroscopy.
AB - Quantitative assessment of cerebral glucose consumption rate (CMRglc) and
tricarboxylic acid cycle flux (VTCA) is crucial for understanding neuroenergetics
under physiopathological conditions. In this study, we report a novel in vivo
Deuterium (2H) MRS (DMRS) approach for simultaneously measuring and quantifying
CMRglc and VTCA in rat brains at 16.4 Tesla. Following a brief infusion of
deuterated glucose, dynamic changes of isotope-labeled glucose,
glutamate/glutamine (Glx) and water contents in the brain can be robustly
monitored from their well-resolved 2H resonances. Dynamic DMRS glucose and Glx
data were employed to determine CMRglc and VTCA concurrently. To test the
sensitivity of this method in response to altered glucose metabolism, two brain
conditions with different anesthetics were investigated. Increased CMRglc (0.46
vs. 0.28 umol/g/min) and VTCA (0.96 vs. 0.6 umol/g/min) were found in rats under
morphine as compared to deeper anesthesia using 2% isoflurane. This study
demonstrates the feasibility and new utility of the in vivo DMRS approach to
assess cerebral glucose metabolic rates at high/ultrahigh field. It provides an
alternative MRS tool for in vivo study of metabolic coupling relationship between
aerobic and anaerobic glucose metabolisms in brain under physiopathological
states.
PMID- 28504001
TI - N-acetylcysteine potentiates diclofenac toxicity in Saccharomyces cerevisiae:
stronger potentiation in ABC transporter mutant strains.
AB - Diclofenac (DCF) adverse reactions involve diverse mechanisms in different
models. We recently demonstrated that DCF-induced toxicity in HepaRG decreases as
they express DCF-metabolizing enzymes. DCF metabolism promotes toxicity in
Saccharomyces cerevisiae expressing heterologous cytochromes-P450. N
Acetylcysteine (NAC) is used to treat diverse medical conditions due to its
multiple properties (antioxidant, metal chelator, thiol-disulfide disruption).
The latter property accounts for its mucolytic effects and broadens its potential
molecular targets to signal transduction proteins, ABC transporters and others.
Interaction of NAC with DCF effects depends on the experimental model. This study
aims to investigate NAC/DCF interaction and the involvement of ABC transporters
in wild type and mutant Saccharomyces cerevisiae. DCF inhibited yeast growth in a
dose- and time-dependent manner and the cells started adapting to DCF 24-h post
treatment. NAC potentiated DCF-induced toxicity if added prior or parallel to
DCF. Pretreatment with NAC increased its potentiation effect and compromised
cells adaption to DCF. Post-treatment with NAC potentiated DCF toxicity without
compromising adaptation. Moreover, mutant strains in ABC transporters Pdr5, Yor1,
Bpt1 or Pdr15, were more sensitive to DCF; while mutant strains in Pdr5, Vmr1 or
Pdr12 were more sensitive to NAC/DCF interaction. DCF +/- NAC elicited on the
mutant strain in Yap1, an oxidative stress-related protein, the same effects as
on the wild type. Therefore, oxidative stress does not seem to be key actor in
DCF toxicity in our model. Our hypothesis is that NAC potentiation effect is at
least due to its ability to disrupt disulfide bridge in proteins required to
overcome DCF toxicity in yeast.
PMID- 28504002
TI - Development and evaluation of a novel score for prediction of large oesophageal
varices in patients with hepatitis c virus-induced liver cirrhosis.
AB - OBJECTIVE: Variceal bleeding is one of the most common life-threatening
complications of liver cirrhosis. This study aimed to develop and evaluate a
predictive score, named Platelet count, Alpha fetoprotein (AFP) and Prothrombin
INR (PAP) for the prediction of large oesophageal varices and to compare PAP
score with eight common liver fibrosis scores (AAR, APRI, GUCI, BRC score, Fibro
Alfa, FIB4, Lok and Fibro-Q) in patients with hepatitis C virus (HCV) induced
liver cirrhosis. METHODS: A total of 277 patients with HCV-induced liver
cirrhosis were evaluated by upper gastrointestinal endoscopy for presence of
varices. Liver biochemical profile, complete blood count, prothrombin time and
AFP were estimated. Stepwise linear discriminant analysis and area under receiver
operating characteristic curves (AUCs) were used to create a predictive score
(PAP score) comprising platelet count, AFP and prothrombin-INR. RESULTS: PAP
score predicts large oesophageal varices in patients with HCV-induced liver
cirrhosis with AUC of 0.85. The optimum cut-off for predicting large oesophageal
varices using ROC curve analysis was 0.27. At this point the PAP score had 77%
sensitivity, 86% specificity, 94% negative predictive value and 84% efficiency.
The diagnostic performances (AUC) of eight common liver fibrosis scores were 0.58
for the AAR score, 0.63 for APRI, 0.66 for GUCI, 0.68 for BRC, 0.72 for Fibro
Alfa, 0.70 for FIB4, 0.72 for Lok and 0.77 for Fibro-Q. CONCLUSION: PAP scores a
non-invasive, inexpensive and simple score that could predict the presence of
large oesophageal varices reducing the need of endoscopy. The PAP score has a
superior AUC score than other scores, suggesting improved clinical value.
PMID- 28504004
TI - Experimental and computational studies on the binding of diazinon to human serum
albumin.
AB - In the present research, the binding properties of diazinon (DZN), as an
organophosphorus herbicide, to human serum albumin (HSA) were investigated using
combination of spectroscopic, electrochemistry, and molecular modeling
techniques. Changes in the UV-Vis and FT-IR spectra were observed upon ligand
binding along with a significant degree of tryptophan fluorescence quenching on
complex formation. The obtained results from spectroscopic and electrochemistry
experiments along with the computational studies suggest that DZN binds to
residues located in subdomains IIA of HSA with binding constant about 1410.9 M-1
at 300 K. From the thermodynamic parameters calculated according to the van't
Hoff equation, the enthalpy change DeltaH degrees and entropy change DeltaS
degrees were found to be -16.695 and 0.116 KJ/mol K, respectively. The primary
binding pattern is determined by hydrophobic interaction and hydrogen binding
occurring in so-called site I of HSA. DZN could slightly alter the secondary
structure of HSA. All of experimental results are supported by computational
techniques such as docking and molecular dynamics simulation using a HSA crystal
model.
PMID- 28504005
TI - How do health behaviour interventions take account of social context? A
literature trend and co-citation analysis.
AB - In recent years, health behaviour interventions have received a great deal of
attention in both research and policy as a means of encouraging people to lead
healthier lives. The emphasis of such interventions has varied over time, in
terms of level of intervention (e.g. individual vs community) and drawing on
different disciplinary perspectives. Recently, a number of critiques have focused
on how health behaviour interventions sometimes sideline issues of social
context, framing health as a matter of individual choice and, by implication, a
personal responsibility. Part of this criticism is that health behaviour
interventions often do not draw on alternative social science understandings of
the structured and contextual aspects of behaviour and health. Yet to our
knowledge, no study has attempted to empirically assess the extent to which, and
in what ways, the health behaviour intervention field has paid attention to
social context. In this article, we undertake this task using bibliometric
techniques in order to map out the health behaviour intervention field. We find
that the number of health behaviour interventions has grown rapidly in recent
years, especially since around 2006, and that references to social science
disciplines and concepts that foreground issues of social context are rare and,
relatively speaking, constitute less of the field post 2006. More quantifiable
concepts are used most, and those more close to the complexities of social
context are mentioned least. The document co-citation analysis suggests that pre
2006, documents referring to social context were relatively diffuse in the
network of key citations, but post 2006 this influence had largely diminished.
The journal co-citation analysis shows less disciplinary overlap post 2006. At
present, health behaviour interventions are continuing to focus on individualised
approaches drawn from behavioural psychology and behavioural economics. Our
findings lend empirical support to a number of recent papers that suggest more
interdisciplinary collaboration is needed to advance the field.
PMID- 28504003
TI - Different metabolic responses induced by long-term interdisciplinary therapy in
obese adolescents related to ACE I/D polymorphism.
AB - INTRODUCTION: The main purpose of the present study was to investigate whether
I/D polymorphism of the ACE gene might affect metabolic changes related to the
metabolic syndrome through a long-term interdisciplinary therapy in obese
adolescents. METHODS: In total, 125 obese adolescents who entered the
interdisciplinary obesity programme were assigned to the following two subgroups:
metabolic syndrome or non-metabolic syndrome. They were evaluated at baseline and
after 1 year. Genomic DNA was extracted from circulating leukocytes. RESULTS:
Subjects with the II genotype in the non-metabolic syndrome group were only to
increase their fat-free mass after therapy. Regarding lipid profile, subjects
with ID and DD genotypes from both groups reduced their low-density lipoprotein
cholesterol levels significantly. The metabolic parameters from the ID and DD
genotypes of the non-metabolic syndrome group showed a significantly improved
insulin response. CONCLUSION: In the present study, we showed that the ACE
polymorphism was able to influence the fat-free mass in the I-carry allele in the
non-metabolic syndrome group positively. In addition, the I-carry allele was able
to improve the insulin resistance of the metabolic syndrome group significantly.
These results suggest that the ACE I/D genotypes can influence, in different
ways, the specific parameters of metabolism among obese adolescents submitted for
long-term interdisciplinary therapy.
PMID- 28504006
TI - A comparative study on the Mn/TiO2-M(M = Sn, Zr or Al) Ox catalysts for NH3-SCR
reaction at low temperature.
AB - A series of TiO2-M(M = Sn, Zr or Al) Ox were prepared and manganese oxide (MnOx)
was supported on the carrier by the traditional impregnation method for low
temperature selective catalytic reduction (SCR) of NOx with ammonia as a
reductant. The obtained catalysts were characterized by XRD, BET, high-resolution
transmission electron microscope (HRTEM), H2-TPR, NH3-TPD, X-ray photoelectron
spectroscopy (XPS) and in situ Fourier-transform infrared (FT-IR) and their
catalytic activities for NOx reduction with NH3 in the presence of SO2 were
investigated comparatively. The results showed that the highest NOx conversion of
over 90% could be obtained with the Mn/Ti-Sn catalyst at a wide range of
temperature window of 150-270 degrees C. The combination of characterization
techniques, such as BET, XRD and HRTEM, revealed that manganese oxides were well
dispersed on Ti-Sn. H2-TPR suggested that Ti-Sn and Ti-Zr supports could enhance
the reduction ability of catalysts. Accordingly, Mn/Ti-Al exhibited worse
activity at low temperature. XPS results were in good agreement with H2-TPR
results, and Mn/Ti-Sn had more surface-reducible species of Mn4+ ions and more
surface-adsorbed oxygen species, which was conducive to SCR reaction. The in situ
FT-IR spectra of NH3 adsorption indicated that all the modified catalysts had
more Lewis acid sites and the amide species at 1506 cm-1 had a certain influence
on the catalytic reaction at low temperature. Mn/Ti-Zr showed a stronger
resistance to SO2 but Mn/Ti-Al was affected more adversely and all the catalysts
could not be restored to the initial catalytic activity after stopping feeding
SO2. NH3-TPD revealed that the total acid amount of the Mn/Ti-Sn sample was
larger than other samples, which indicated that the Ti-Sn solid solution could
provide more surface acid sites over the catalyst.
PMID- 28504007
TI - Can we afford not to prevent MS-related disability?
PMID- 28504008
TI - Maternal resolution of preterm birth from 1 to 18 months.
AB - Preterm birth can be traumatic for some mothers, involving feelings of grief over
the hoped-for full-term pregnancy. In this longitudinal study, we interviewed 50
mothers of preterm infants, using the reaction to diagnosis interview when their
child was 1 month and 18 months old. We examined change and stability in
resolution status over time. Additionally, we explored possible predictors of
resolution trajectories between 1 and 18 months. Findings indicated that
resolution at 1 month was not yet common. The rate of resolution at 18 months was
62.6%, compared with 38.2% at 1 month. Prenatal precursors of preterm birth,
lower medical neonatal risk, and lower maternal stress at 1 month significantly
differentiated mothers who attained resolution as early as at 1 month from those
who were unresolved at 1 and 18 months. Lower maternal stress at 1 month was the
only predictor that significantly differentiated initially unresolved mothers who
later attained resolution from those who remained unresolved at 18 months.
Discussion focuses on maternal stress, which may mark a subgroup of mothers of
preterm infants who are at risk of being unresolved through the first 18 months,
and who may benefit from resolution-focused intervention.
PMID- 28504009
TI - The redox couple avarol/avarone in the fight with malignant gliomas: the case
study of U-251 MG cells.
AB - This study aimed to screen in vitro antitumour activity of the redox couple
avarol/avarone against the human malignant glioma cell line U-251 MG for the
first time. Compared both with avarol and positive controls used (temozolomide
and doxorubicin), avarone was found to be the most active compound with IC50
value below 1 MUM (IC50 0.68 +/- 0.04 MUM, 96 h). Considerable less DNA damage in
the cells treated with avarol and avarone vs. doxorubicin (105 & 123% vs. 299%,
respectively; untreated U-251 MG cells were used as a control, 100%), coupled
with no sign of cytotoxicity against the normal human foetal lung fibroblast MRC
5 cells (IC50 > 100 MUM), has actually pointed out the importance of this marine
sesquiterpenoid quinone structure as a promising lead compound in development of
novel brain chemotherapeutics.
PMID- 28504010
TI - Effects of selective serotonin reuptake inhibitors on intraocular pressure and
anterior segment parameters in open angle eyes.
AB - PURPOSE: To evaluate the short- and long-term effects of selective serotonin
reuptake inhibitors (SSRIs) on intraocular pressure (IOP) and anterior segment
parameters in open angle eyes. MATERIALS AND METHODS: This cross-sectional study
included 325 eyes of 166 subjects. Subjects were divided into three groups: Group
1 included 116 eyes of 58 patients receiving SSRIs for 1 week-6 months, Group 2
included 102 eyes of 53 patients receiving SSRIs for longer than 6 months and
Group 3 included 107 eyes of 55 healthy subjects not receiving any drugs. All of
the patients receiving SSRIs were diagnosed as major depressive disorder. All
groups were chosen to be similar in terms of age and gender. All patients
underwent a detailed ophthalmologic examination including IOP measurement by
Goldmann applanation tonometer and gonioscopy. Anterior segment parameters
including pupil diameter (PD), central corneal thickness (CCT), anterior chamber
depth (ACD), anterior chamber volume (ACV), and anterior chamber angle (ACA) were
assessed by a Scheimpflug system. RESULTS: Pupil diameter was significantly
larger in patients receiving SSRIs for <6 months and >=6 months than the control
subjects (3.53 +/- 0.71 mm, 3.48 +/- 0.60 mm versus 3.11 +/- 0.72 mm, p < 0.05)
but this effect was independent from the duration of SSRI treatment. IOP was
significantly lower in patients receiving SSRIs for <6 months and >=6 months than
the control group (16.04 +/- 2.17 mm Hg, 16.11 +/- 2.13 mm Hg versus 17.34 +/-
2.15 mmHg, p < 0.05), but there were no statistically significant differences
between the patients receiving SSRIs for <6 months and >=6 months. There were no
statistically significant differences between the patient and the control group
in values of CCT, ACD, ACV and ACA. The ACAs were measured between 25 degrees
and 55 degrees with Scheimpflug system and also classified as grade 3-4 (Shaffer
system) by gonioscopy. CONCLUSIONS: Selective serotonin reuptake inhibitors cause
mydriasis which is persistent during the treatment. In depression patients with
open angle eyes, short- and long-term use of SSRIs leads to decrease in IOP.
PMID- 28504011
TI - The future of oncology therapeutics.
PMID- 28504012
TI - Inpatient glycemic management in internal medicine: an observational multicenter
study in Nanjing, China.
AB - AIMS: To evaluate the prevalence of hyperglycemia among inpatients in internal
medicine, and specifically, to assess the glycemic management of inpatients in
non-endocrinology departments in three large urban hospitals in China. METHODS: A
multicenter observational study was conducted using electronic health records,
and a survey of 1939 patients who were admitted to internal medicine units and
followed until discharge. Those with previously diagnosed diabetes, newly
diagnosed diabetes, or impaired fasting glucose were included. Aspects of
glycemic management examined were (a) hyperglycemia, (b) endocrinology
consultation for hyperglycemia and (c) hypoglycemia. RESULTS: The prevalence of
hyperglycemia in internal medicine was 45.7% (886 out of 1939). A total of 741
(83.6%) patients were treated by non-endocrinology departments; of those, 230
(31.1%) were in poor glycemic control and needed an endocrinology consultation.
Yet only 57 (24.8%) received one. In 4 cases, the physician did not follow the
consultants' advice. Among the remaining 53 consulted patients, 35 (66.1%) were
still in poor glycemic control, yet only about half received a second
consultation. Finally, among patients treated in non-endocrinology departments,
58 (7.8%) had hypoglycemia; less than half retested their blood glucose after
treatment. CONCLUSIONS: The majority of patients with hyperglycemia were in non
endocrinology departments. Their glycemic management was poor; the endocrinology
consultation rate was low and the result was suboptimal. Also, the management of
hypoglycemia was not ideal. Therefore, improving glycemic management is urgently
needed in Chinese hospitals.
PMID- 28504013
TI - Anti-influenza effect of the major flavonoids from Salvia plebeia R.Br. via
inhibition of influenza H1N1 virus neuraminidase.
AB - To determine the compounds responsible for its anti-influenza activities, we
isolated the three flavonoids, 6-hydroxyluteolin 7-O-beta-d-glucoside (1),
nepitrin (2), homoplantaginin (3) from the MeOH extract of Salvia plebeia R.Br.
and identified them by comparing the spectroscopic data with that reported in the
literature. The contents of the three flavonoids in the whole extract were 108.74
+/- 0.95, 46.26 +/- 2.19, and 69.35 +/- 1.22 mg/g for 6-hydroxyluteolin 7-O-beta
d-glucoside, nepitrin, and homoplantaginin, respectively, which demonstrates that
they are the major constituents of this plant. The three flavonoids were
evaluated for their inhibitory activities against influenza virus H1N1 A/PR/9/34
neuraminidase and H1N1-induced cytopathic effect (CPE) on Madin-Darby canine
kidney (MDCK) cells. Our results demonstrated the following arrangement for their
anti-influenza activities: nepitrin (2) > 6-hydroxyluteolin 7-O-beta-d-glucoside
(1) > homoplantaginin (3). The potent inhibitory activities of these flavonoids
against influenza suggested their potential to be developed as novel anti
influenza drugs in the future.
PMID- 28504014
TI - The development of a patient-specific method for physiotherapy goal setting: a
user-centered design.
AB - PURPOSE: To deliver client-centered care, physiotherapists need to identify the
patients' individual treatment goals. However, practical tools for involving
patients in goal setting are lacking. The purpose of this study was to improve
the frequently used Patient-Specific Complaints instrument in Dutch
physiotherapy, and to develop it into a feasible method to improve physiotherapy
goal setting. METHODS: An iterative user-centered design was conducted in co
creation with the physiotherapists and patients, in three phases. Their needs and
preferences were identified by means of group meetings and questionnaires. The
new method was tested in several field tests in physiotherapy practices. RESULTS:
Four main objectives for improvement were formulated: clear instructions for the
administration procedure, targeted use across the physiotherapy process, client
activating communication skills, and a client-centered attitude of the
physiotherapist. A theoretical goal-setting framework and elements of shared
decision making were integrated into the new-called, Patient-Specific Goal
setting method, together with a practical training course. CONCLUSIONS: The user
centered approach resulted in a goal-setting method that is fully integrated in
the physiotherapy process. The new goal-setting method contributes to a more
structured approach to goal setting and enables patient participation and goal
oriented physiotherapy. Before large-scale implementation, its feasibility in
physiotherapy practice needs to be investigated. Implications for rehabilitation
Involving patients and physiotherapists in the development and testing of a goal
setting method, increases the likelihood of its feasibility in practice. The
integration of a goal-setting method into the physiotherapy process offers the
opportunity to focus more fully on the patient's goals. Patients should be
informed about the aim of every step of the goal-setting process in order to
increase their awareness and involvement. Training physiotherapists to use a
patient-specific method for goal setting is crucial for a correct application.
PMID- 28504015
TI - Laparoscopic Surgery in Patients on Peritoneal Dialysis: A Review of the
Literature.
AB - Peritoneal dialysis (PD) is an effective renal replacement therapy for the
treatment of end-stage renal disease. Patients on PD undergoing abdominal open
surgery often fail to resume PD. Laparoscopic surgery has recently become a
serious alternative to open surgery in patients on PD to treat different
abdominal pathologies. However, only a few studies have reported successful
procedures without Tenckhoff catheter removal. The aim of this review is to
describe how a laparoscopic technique can allow PD patients to deal with
abdominal surgery without shifting to hemodialysis. Only 50 cases of laparoscopic
surgical intervention in PD patients have been published to our knowledge. These
case series largely concern laparoscopic cholecystectomies, appendectomies,
nephrectomies, colectomies, and bariatric procedures. The reported cases show how
laparoscopic surgery can be accepted as a valid option for several abdominal
surgical procedures in patients on PD with good outcomes and early resumption of
PD.
PMID- 28504016
TI - DNA isolation by galactoacrylate-based nano-poly(HEMA-co-Gal-OPA) nanopolymers.
AB - Isolation of DNA is one of the important processes for biotechnological
applications such as investigation of DNA structures and functions, recombinant
DNA preparations, identification of genetic factors and diagnosis and treatment
of genetic disorders. The aim of this study was to synthesis and characterizes
the galactoacrylate based nanopolymers with high surface area and to investigate
the usability of these synthesized nanopolymers for DNA isolation studies.
Nanopolymers were synthesized by the surfactant free emulsion polymerization
technique by using the monomers of 2-hydroxyl ethylmethacrylate and 6-O-(2'
hydroxy-3'-acryloyloxypropyl)-1,2:3,4-di-O-isopropylidene-alpha-D
galactopyranose. Galactoacrylate origin of these newly synthesized nanopolymers
increased the interaction between DNA and nanopolymers. Prepared nanopolymers
were characterized by SEM, FT-IR and ZETA sizer analysis. Synthesized
nanopolymers were spherical, and their average particle size was about 246.8 nm.
Adsorption of DNA onto galactoacrylate based nanopolymers was investigated by
using different pHs, temperatures, ionic strength, DNA concentrations and
desorption studies and maximum DNA adsorption was found to be as 567.12 mg/g
polymer at 25 degrees C, in pH 5.0 acetate buffer. Reusability was investigated
for 5 successive reuse and DNA adsorption capacity decreased only about 10% at
the end of the 5th reuse.
PMID- 28504017
TI - Chemical composition, antioxidant and cytotoxic activities of extracts from the
leaves of Smilax brasiliensis Sprengel (Smilacaceae).
AB - The antioxidant and cytotoxic activities of petroleum ether and methanol
extracts, fatty acids and methyl esters from leaves of Smilax brasiliensis were
evaluated, and the composition of the extracts was determined. Palmitic, linoleic
and linolenic acids were major components of the extracts. For antioxidant
activity, all samples exhibited IC50 values lower than BHT (2,6-di-tert-butyl-4
methylphenol). The extracts, fatty acids and methyl esters from S. brasiliensis
presented no toxicity to larvae of the brine shrimp, Artemia salina. Among the
purified substances, only methyl linolenate showed toxicity (LD50 = 21.47
MUg/mL). This study showed, for the first time, the composition of petroleum
ether and methanol extracts from S. brasiliensis leaves, as well as the
antioxidant and cytotoxic activities of extracts, fatty acids and methyl esters.
PMID- 28504018
TI - Comparison of modelling accuracy with and without exploiting automated optical
monitoring information in predicting the treated wastewater quality.
AB - Traditionally the modelling in an activated sludge process has been based on
solely the process measurements, but as the interest to optically monitor
wastewater samples to characterize the floc morphology has increased, in the
recent years the results of image analyses have been more frequently utilized to
predict the characteristics of wastewater. This study shows that the traditional
process measurements or the automated optical monitoring variables by themselves
are not capable of developing the best predictive models for the treated
wastewater quality in a full-scale wastewater treatment plant, but utilizing
these variables together the optimal models, which show the level and changes in
the treated wastewater quality, are achieved. By this early warning, process
operation can be optimized to avoid environmental damages and economic losses.
The study also shows that specific optical monitoring variables are important in
modelling a certain quality parameter, regardless of the other input variables
available.
PMID- 28504019
TI - Midterm Outcomes of Pharmacomechanical Thrombectomy in the Treatment of Lower
Extremity Deep Vein Thrombosis With a Rotational Thrombectomy Device.
AB - BACKGROUND: The purpose of this study was to assess the safety and efficacy with
midterm outcomes of pharmacomechanical thrombectomy (PMT) performed by using a
relatively new thrombectomy device in the treatment of lower extremity deep vein
thrombosis (DVT). METHODS: Between February 2014 and February 2016, a total of 46
patients with lower extremity DVT were treated with PMT by using Cleaner
rotational thrombectomy system. Preprocedural, intraprocedural, postprocedural,
and follow-up records of patients were collected and retrospectively analyzed.
RESULTS: Mean age of patients was 50.5 (14.8) years, and 58.7% of them were
female. Technical success rate of procedure was 91.3%. Mean procedure time was
81.8 (40.3) minutes. Early clinical improvement was observed in all patients with
successful treatment. No serious adverse event related to procedure and mortality
was observed. Mean follow-up time was 16.0 (7.9) months. Reocclusion was observed
in 7 (17.5%) patients during the follow-up period. Venous patency rates of
patients at 1-, 3-, 6-, and 12-month follow-up visits were 95%, 92.5%, 89.7%, and
79.5%, respectively. Mild, moderate, and severe postthrombotic syndrome were
observed in 8 (20%) patients, 4 (10%) patients, and 1 (2.5%) patient,
respectively. Postthrombotic syndrome-free survival rate was 67.5%. CONCLUSION:
Cleaner rotational thrombectomy system appears to be safe and effective in the
treatment of lower extremity DVT. Further larger randomized studies are needed to
determine the long-term outcomes of this treatment modality.
PMID- 28504020
TI - Propoxur-induced oxidative DNA damage in human peripheral blood mononuclear
cells: protective effects of curcumin and alpha-tocopherol.
AB - The present study enumerates the attenuating effects of curcumin and alpha
tocopherol against propoxur induced oxidative DNA damage in human peripheral
blood mononuclear cells (PBMC). Cultured cells were isolated from peripheral
blood of healthy volunteers, and were exposed to varying concentrations of
propoxur (0-21 MUg/ml) for 6, 12, and 24 h, and in combination with curcumin (9.2
MUg/ml) or alpha-tocopherol (4.3 MUg/ml) or both. Cytotoxic effect of propoxur
was examined by MTT assay. The role of oxidative stress beneath the cytotoxicity
of propoxur was evaluated by the measurement of reduced glutathione (GSH),
malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) levels in cell
lysate. A concentration-dependent cell death, depletion of GSH, an increase in
the level of both MDA and 8-OH-dG were observed. Co-treatment with curcumin or
alpha-tocopherol significantly attenuates depleted GSH, decrease in MDA and 8-OH
dG levels in propoxur exposed cells (p < 0.05). The results of the present study
provide experimental evidence of involvement of oxidative stress in propoxur
mediated genotoxicity in human PBMC and highlight the antioxidant role of
curcumin and alpha-tocopherol following propoxur exposure.
PMID- 28504021
TI - The Theory of Dyadic Morality: Reinventing Moral Judgment by Redefining Harm.
AB - The nature of harm-and therefore moral judgment-may be misunderstood. Rather than
an objective matter of reason, we argue that harm should be redefined as an
intuitively perceived continuum. This redefinition provides a new understanding
of moral content and mechanism-the constructionist Theory of Dyadic Morality
(TDM). TDM suggests that acts are condemned proportional to three elements: norm
violations, negative affect, and-importantly-perceived harm. This harm is dyadic,
involving an intentional agent causing damage to a vulnerable patient (A->P). TDM
predicts causal links both from harm to immorality (dyadic comparison) and from
immorality to harm (dyadic completion). Together, these two processes make the
"dyadic loop," explaining moral acquisition and polarization. TDM argues against
intuitive harmless wrongs and modular "foundations," but embraces moral pluralism
through varieties of values and the flexibility of perceived harm. Dyadic
morality impacts understandings of moral character, moral emotion, and
political/cultural differences, and provides research guidelines for moral
psychology.
PMID- 28504022
TI - Safinamide for the treatment of Parkinson's disease.
AB - INTRODUCTION: The major unmet needs in the medical treatment of Parkinson disease
(PD) are reduction of motor side effects from dopaminergic drugs, management of
non-motor symptoms and disease modification. Areas covered: Motor fluctuations
and OFF periods are a significant determinant of quality of life in PD and
reducing their duration and severity can significantly improve motor function.
This aim may be partly facilitated by the development of effective adjunctive
drugs for dopamine replacement. Safinamide (Xadago), which is a first generation
anticonvulsant, has pharmacological properties which are of interest in the
context of neurodegenerative diseases, leading to research into its potential as
an adjunct to levodopa in PD. Expert opinion: Although its mechanism has not been
fully defined, safinamide provides enhanced symptom control of motor function in
advanced PD and improves quality of life.
PMID- 28504023
TI - Twelve tips for effective body language for medical educators.
AB - BACKGROUND: A significant proportion of human communication is nonverbal.
Although the fields of business and psychology have significant literature on
effectively using body language in a variety of situations, there is limited
literature on effective body language for medical educators. AIM: To provide 12
tips to highlight effective body language strategies and techniques for medical
educators. METHOD: The tips provided are based on our experiences and reflections
as clinician-educators and the available literature. RESULTS: The 12 tips
presented offer specific strategies to engage learners, balance learner
participation, and bring energy and passion to teaching. CONCLUSIONS: Medical
educators seeking to maximize their effectiveness would benefit from an
understanding of how body language affects a learning environment and how body
language techniques can be used to engage audiences, maintain attention, control
challenging learners, and convey passion for a topic. Understanding and using
body language effectively is an important instructional skill.
PMID- 28504024
TI - Detection of driver and subclonal mutations in myelofibrosis: clinical impact on
pharmacologic and transplant based treatment strategies.
AB - INTRODUCTION: Myelofibrosis (MF) is the most aggressive form among Philadelphia
negative (Ph-) myeloproliferative neoplasms (MPNs). In the last years, the
mutational landscape of MF has expanded remarkably by the identification of
additional recurrent mutations, called subclonal mutations. Areas covered: Here
we describe the available data about the currently identified subclonal mutations
and their prognostic value in MF patients. We also review the practical value of
including such molecular information in available prognostic models for both
outcome prediction and possibly treatment decision with regards to transplant
indication. Lastly, we covered the available data on the application of molecular
markers for minimal residual disease (MRD) monitoring after transplantation.
Expert commentary: The demonstration of the prognostic value of additional
mutations suggests to define this molecular profile at diagnosis and when an
allogeneic transplant can be advised, particularly in younger patients. The
presence of molecular markers might offer the possibility to evaluate the depth
of remission and to monitor MRD after transplantation. Prospective clinical
studies are needed to validate the use of this molecular data in the routine
clinical practice.
PMID- 28504025
TI - The preclinical discovery of vosaroxin for the treatment of acute myeloid
leukemia.
AB - INTRODUCTION: Acute myeloid leukemia (AML) represents a disease with a very poor
outcome and remains an area of significant unmet need necessitating novel
therapeutic strategies. Among novel therapeutic agents, vosaroxin is a first-in
class anticancer quinolone derivative that targets topoisomerase II and induces
site-selective double-strand breaks in DNA, leading to tumor cell apoptosis.
Areas covered: Herein, the authors provide a comprehensive review of the
preclinical development of vosaroxin. This includes coverage of vosaroxin's
mechanism of action in addition to its pharmacology and of the main studies
reported over the past few years with vosaroxin when used to treat adult AML.
Expert opinion: Given that vosaroxin is associated with fewer potential side
effects, it may be of benefit to elderly patients with relapsed/refractory AML
and to those with additional comorbidities who have previously received an
anthracycline and cytarabine combination. Furthermore, vosaroxin also was seen to
be active in multidrug-resistant preclinical models. However, further studies
have to be performed to better evaluate its place in the armamentarium against
AML.
PMID- 28504026
TI - The influence of time horizon on results of cost-effectiveness analyses.
AB - BACKGROUND: Debates persist on the appropriate time horizon from a payer's
perspective and how the time horizon in cost-effectiveness analysis (CEA)
influences the value assessment. METHODS: We systematically reviewed the Tufts
Medical Center CEA Registry and identified US-based studies that used a payer
perspective from 2005-2014. We classified the identified CEAs as short-term (time
horizon <= 5 years) and long-term (> 5 years), and examined associations between
study characteristics and the specified time horizon. We also developed case
studies with selected interventions to further explore the relationship between
time horizon and projected costs, benefits, and incremental cost-effectiveness
ratios (ICER). RESULTS: Among 782 identified studies that met our inclusion
criteria, 552 studies (71%) utilized a long-term time horizon while 198 studies
(25%) used a short-term horizon. Among studies that employed multiple time
horizons, the extension of the time horizon yielded more favorable ICERs in 19
cases and less favorable ICERs in 4 cases. Case studies showed the use of a
longer time horizon also yielded more favorable ICERs. CONCLUSION: The assumed
time horizon in CEAs can substantially influence the value assessment of medical
interventions. To capture all consequences, we encourage the use of time horizons
that extend sufficiently into the future.
PMID- 28504027
TI - Epidemiology and comorbidity of obsessive-compulsive disorder in late
adolescence: a cross-sectional study in senior high schools in Greece.
AB - OBJECTIVE: The aim of this study was to examine the epidemiology, comorbidity and
use of health services of obsessive-compulsive disorder (OCD) and subclinical
obsessive-compulsive symptoms in late adolescence. METHODS: A total of 2427
adolescents attending senior high schools in Greece were selected for a detailed
psychiatric interview using the revised clinical interview schedule (CIS-R). Use
of alcohol, nicotine and cannabis, and several socio-demographic and socio
economic variables were also assessed. RESULTS: The prevalence of OCD was 1.39%
(95% confidence interval [CI]: 1.05-1.84) while that of subclinical obsessive
compulsive symptoms was 2.77% (2.22-3.45). There was a female preponderance for
subclinical symptoms. Financial difficulties of the family was the only socio
demographic variable that was significantly associated with OCD but not with
subclinical symptoms. The pattern of comorbidity was similar for both conditions
but milder in the subclinical form. About one in three reported use of general
health services and one in ten use of psychiatric services. CONCLUSIONS: OCD and
subclinical obsessive-compulsive symptoms were relatively common. Comorbidity
with other psychiatric disorders and use of substances was considerable even in
subclinical status, but use of specialised health services was small. Clinical
and research implications are discussed.
PMID- 28504028
TI - Essential competencies in global health research for medical trainees: A
narrative review.
AB - INTRODUCTION: Participation in short-term educational experiences in global
health (STEGHs) among medical trainees is increasingly accompanied by interest in
conducting research while abroad. Because formal training in both global health
and research methods is currently under-represented in most medical curricula,
trainees are often unfamiliar with the knowledge, attitudes, and skills necessary
to design and conduct research successfully. This narrative review identifies
essential global health research competencies for medical trainees engaged in
STEGHs. METHODS: The authors searched the literature using the terms global
health, competency, research, research methods/process/training, scholarly
project, medical student, and medical education/education. Because articles
directly addressing global health research competencies for medical trainees were
limited, the authors additionally drew on the broader literature addressing
general research competencies and global health competencies. FINDINGS: Articles
yielded by the literature search, combined with established guidelines in
research ethics and global health ethics, were used to identify six core domains
and twenty discrete competencies fundamental to global health research at a level
appropriate for medical trainees enrolled in STEGHs. Consideration was given to
diverse research modalities, varying levels of training, and the availability of
mentoring and on-site support. DISCUSSION: Research may provide important
benefits to medical trainees and host partners. These competencies provide a
starting point; however, circumstances at any host site may necessitate
additional competencies specific to that setting. These competencies are also
limited by the methodology employed in their development and the need for
additional perspectives from host partners. CONCLUSIONS: The competencies
identified outline basic knowledge, attitudes, and skills necessary for medical
trainees to conduct limited global health research while participating in STEGHS.
They may also be used as a basis for curriculum development, assessment, and
research capacity development.
PMID- 28504029
TI - Obstetric brachial plexus palsy: a population-based retrospective case-control
study and medicolegal considerations.
AB - AIMS: The aim of this study was to examine 24 cases of obstetric brachial plexus
palsy (OBPP) in 41,002 deliveries occurred at San Camillo-Forlanini Hospital in
Rome, during the period 2000-2012. MATERIALS AND METHODS: A population-based
retrospective case-control study was designed and the database of the hospital
was searched; for each case, maternal and fetal records were examined and some
risk factors were evaluated. RESULTS: A statistically significant association
between the 24 cases OBPP and the following risk factors: primiparity (p < .014),
birth weight (p < .002), maternal age (p < .02), diabetes (p < .03) and shoulder
dystocia (p < .003) was found, moreover all the OBPP cases were recorded only in
vaginal deliveries. CONCLUSIONS: The absence of OBPP cases in cesarean deliveries
highlighted in this study supports the option of proposing an elective cesarean
in the presence of known risk factors after a full disclosure with the mother of
risks and benefits in order to obtain a valid consent. Furthermore, when cases of
OBPP occur, communication between the physician and the parents of newborns is
crucial and it may represent a valid risk-management tool to reduce malpractice
lawsuits.
PMID- 28504030
TI - Practical recommendations for the choice of anticoagulants in the management of
patients with atrial fibrillation on ibrutinib.
AB - The management of AF represents a major challenge in patients with CLL,
especially in elderly patients with multiple comorbidities who are representative
of the majority of patients with CLL. This is especially complex in the case of
ibrutinib. Many anticoagulants have potential for pharmacological interaction
with ibrutinib, and ibrutinib itself has antiplatelet properties. Use of
ibrutinib therapy in these patients mandates review and revision of the need for
anticoagulation and best anticoagulant to use. Herein, we review the current
knowledge of the metabolism of common anticoagulants and how they may interact
with ibrutinib.
PMID- 28504031
TI - Topical 0.25% desoximetasone spray efficacy for moderate to severe plaque
psoriasis: a randomized clinical trial.
AB - BACKGROUND: Traditionally, ointments were the vehicle of choice for psoriasis.
Poor adherence of traditional vehicles limits the use of topical corticosteroids.
Alternative formulations have gained popularity due to their ease of application,
improved adherence and efficacy. OBJECTIVE: To evaluate the efficacy of topical
desoximetasone 0.25% spray formulation in extensive psoriasis. METHODS: This
multicenter, double-blinded, randomized trial compared twice daily topical 0.25%
desoximetasone spray to placebo in subjects >=18 with moderate to severe plaque
psoriasis. Primary outcome of the study was the proportion of subjects in each
group that achieved clinical success (Physician Global Assessment [PGA] of 0 or
1) and/or treatment success at (target lesion score of 0 or 1) day 28. RESULTS:
One-hundred-and-twenty subjects were enrolled. At baseline, 75.0% and 73.3% of
the treatment and placebo group had at least moderate PGA, respectively. Clinical
success in the intended-to treat and placebo group was 30% and 5% (p = .0003),
respectively; treatment success was 39% and 7% (p < .0001), respectively.
LIMITATIONS: The lack of standardized outcomes for topical psoriasis treatments
limits the ability to compare the results to other treatments. CONCLUSIONS:
Topical desoximetasone spray provides rapid control of moderate to severe
psoriasis lesions and may be considered for patients awaiting approval of
biologicals. TRIAL REGISTRATION: Clinical Trial was registered at
clinicaltrial.gov: NCT01206387.
PMID- 28504032
TI - Targeting peroxisome proliferator-activated receptors: a novel strategy for
Philadelphia chromosome-positive leukemia cells.
PMID- 28504033
TI - Salvage chemotherapy and autologous stem cell transplantation for peripheral T
cell lymphoma: a subset analysis of the Canadian Cancer Trials Group LY.12
randomized phase 3 study.
AB - Peripheral T-cell lymphoma (PTCL) is a rare, heterogeneous malignancy. Of the 619
patients with relapsed and refractory (R/R) aggressive lymphoma enrolled in the
Canadian Cancer Trials Group LY.12 phase 3 trial, 59 (9.5%) had PTCL. Among
these, 81% had advanced stage disease, 41% had an International Prognostic Score
>=3, and 41% were refractory to primary therapy. Within the PTCL cohort, the
overall response rate after two cycles of salvage chemotherapy was 36%; no
difference was observed between dexamethasone, cytarabine, cisplatin (10/30,
33%), and gemcitabine, cisplatin, dexamethasone (11/29, 38%) therapy. At one
year, event-free survival (EFS) was 16% and overall survival (OS) was 28%. For
PTCL patients, who received autologous stem cell transplant, two-year EFS and OS
were 21% and 42%, respectively. Patients with PTCL had inferior OS (HR 0.49, p <
.0001) and EFS (HR 0.53, p < .0001) compared to B-cell lymphoma. Outcomes for
patients with R/R PTCL are poor with currently available therapies.
PMID- 28504034
TI - A simulation of loading doses for vancomycin continuous infusion regimens in
intensive care.
AB - BACKGROUND: Delayed achievement of target vancomycin serum concentrations may
adversely affect clinical outcomes. The objective of this retrospective study was
to compare the prediction accuracy of different body weight descriptors for
volume of distribution and to propose an optimal loading dose (LD) for continuous
infusion regimens in adults. METHODS: Pharmacokinetic variables were computed
using one-compartmental analysis. Simulated LDs of vancomycin were evaluated for
each patient. RESULTS: Volume of distribution, clearance, and half-life median
values (interquartile range) for vancomycin in the study population (n = 30) were
0.45 (0.39-0.61) L.kg-1, 0.026 (0.015-0.040) L.h-1.kg-1, and 10.3 (7.7-21.3) h,
respectively. The observed volume of distribution was better predicted by total
body weight (TBW) than by the ideal body weight or the adjusted body weight.
CONCLUSIONS: An LD of 10.7 mg per kg TBW was optimal in our study population.
Using this LD, 17.9% of simulated vancomycin serum levels were just below the
therapeutic range, only 10.7% concentrations exceeded the target range and no
concentration was toxic. The use of a LD would lead to reduced median time to
reach target concentrations from 17 to 1 h.
PMID- 28504035
TI - Bleomycin pulmonary toxicity does not adversely affect the outcome of patients
with Hodgkin lymphoma.
AB - Bleomycin pulmonary toxicity (BPT) is a well-described complication of bleomycin
containing regimens. Previous data on risk factors and the impact of BPT on
survival in Hodgkin lymphoma (HL) were conflicting. We reviewed 253 HL patients
treated with adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) at the
Princess Margaret Hospital from 1999 to 2009 to examine the incidence and risk
factors for BPT, and the effect of BPT on survival. BPT was defined by pulmonary
symptoms, bilateral interstitial infiltrates on computed tomography, and the
absence of infection. Kaplan-Meier estimates were used to compare overall
survival (OS) and progression-free survival (PFS) between groups. The incidence
of BPT was low (11%). Age >=45 (OR = 2.5) and granulocyte colony-stimulating
factor use (OR = 3.6) were identified as predictors of BPT on multivariable
logistic models. At a follow-up of 5 years, OS and PFS were 88% and 82%,
respectively. Neither BPT nor bleomycin discontinuation had significant impact on
survival outcomes.
PMID- 28504036
TI - Combination therapy of BRAF inhibitors for advanced melanoma with BRAF V600
mutation: a systematic review and meta-analysis.
AB - BACKGROUND: Although BRAF inhibitors have been used to treat advanced melanoma
with BRAF mutation, combination strategies are suggested due to acquired
resistance to BRAF inhibitors. OBJECTIVE: To assess the efficacy of BRAF
inhibitor-based combination therapy for the treatment of advanced melanoma with
BRAF mutation. METHODS: We conducted a systematic review and meta-analysis of
studies that compared BRAF inhibitor-based combination therapy with BRAF
inhibitor monotherapy. We searched MEDLINE, EMBASE, the Cochrane Library and
relevant conference proceedings. The random-effects inverse variance and Mantel
Haenszel methods were used to pool the results. RESULTS: Four randomized
controlled trials and one cohort study were identified. A combination therapy
with BRAF inhibitors and MEK inhibitors was used in all studies. The combined
hazard ratios of overall survival (OS) and progression-free survival (PFS)
comparing combination therapy with monotherapy were 0.70 [95% confidence interval
(CI) 0.62-0.78] and 0.59 (95% CI 0.55-0.63), respectively. The combined risk
ratio of objective response rate (ORR) was 1.30 (95% CI 1.20-1.40), which meant
more patients achieved complete/partial responses in combination therapy group
than those in the monotherapy group. CONCLUSIONS: Combination therapy with BRAF
inhibitors and MEK inhibitors significantly improved OS, PFS, and ORR in patients
with advanced melanoma with BRAF mutation.
PMID- 28504038
TI - Corrigendum to "Monitoring the World Health Organization Global Target 2025 for
exclusive breastfeeding: Experience from the United States".
PMID- 28504037
TI - Plasma butyrylcholinesterase activity: a possible biomarker for differential
diagnosis between Alzheimer's disease and dementia with Lewy bodies?
AB - Butyrylcholinesterase (BChE) is an enzyme encoded by BCHE gene, responsible for
secondary hydrolysis of the acetylcholine. K and -116A BCHE variants were
associated with decrease in plasma BChE activity, and their influence has been
investigated in diseases with a cholinergic deficit such as Alzheimer's disease
(AD) and dementia with Lewy bodies (DLB). In order to check the influence of BCHE
genetic variants on enzymatic activity, all patients and controls were genotyped
for K and -116A variants. We found lower plasma BChE activity in DLB patients
compared to elderly controls and to AD independent of the presence of K or -116A
variants. Our results suggest that the reduction of total plasma BChE activity is
probably associated with a feedback mechanism and provides a future perspective
of using this enzyme as a possible plasmatic marker for differential diagnosis
between AD and DLB.
PMID- 28504039
TI - Frozen bereavement.
PMID- 28504040
TI - Facebook addiction and loneliness in the post-graduate students of a university
in southern India.
AB - BACKGROUND: Facebook is a social networking site (SNS) for communication,
entertainment and information exchange. Recent research has shown that excessive
use of Facebook can result in addictive behavior in some individuals. AIM: To
assess the patterns of Facebook use in post-graduate students of Yenepoya
University and evaluate its association with loneliness. METHODS: A cross
sectional study was done to evaluate 100 post-graduate students of Yenepoya
University using Bergen Facebook Addiction Scale (BFAS) and University of
California and Los Angeles (UCLA) loneliness scale version 3. Descriptive
statistics were applied. Pearson's bivariate correlation was done to see the
relationship between severity of Facebook addiction and the experience of
loneliness. RESULTS: More than one-fourth (26%) of the study participants had
Facebook addiction and 33% had a possibility of Facebook addiction. There was a
significant positive correlation between severity of Facebook addiction and
extent of experience of loneliness ( r = .239, p = .017). CONCLUSION: With the
rapid growth of popularity and user-base of Facebook, a significant portion of
the individuals are susceptible to develop addictive behaviors related to
Facebook use. Loneliness is a factor which influences addiction to Facebook.
PMID- 28504043
TI - Insight in psychosis: Standards, science, ethics and value judgment.
AB - BACKGROUND: The clinical assessment of insight solely employs biomedical
perspectives and criteria to the complete exclusion of context and culture and to
the disregard of values and value judgments. AIM: The aim of this discussion
article is to examine recent research from India on insight and explanatory
models in psychosis and re-examine the framework of assessment, diagnosis and
management of insight and explanatory models. METHODS: Recent research from India
on insight in psychosis and explanatory models is reviewed. RESULTS: Recent
research, which has used longitudinal data and adjusted for pretreatment
variables, suggests that insight and explanatory models of illness at baseline do
not predict course, outcome and treatment response in schizophrenia, which seem
to be dependent on the severity and quality of the psychosis. It supports the
view that people with psychosis simultaneously hold multiple and contradictory
explanatory models of illness, which change over time and with the trajectory of
the illness. It suggests that insight, like all explanatory models, is a
narrative of the person's reality and a coping strategy to handle with the varied
impact of the illness. CONCLUSION: This article argues that the assessment of
insight necessarily involves value entailments, commitments and consequences. It
supports a need for a broad-based approach to assess awareness, attribution and
action related to mental illness and to acknowledge the role of values and value
judgment in the evaluation of insight in psychosis.
PMID- 28504044
TI - Epigenetics and developmental psychiatry.
PMID- 28504046
TI - Formulation and characterization of Phospholipon 90 G and tween 80 based
transfersomes for transdermal delivery of eprosartan mesylate.
AB - The objective of the current study was to formulate the eprosartan mesylate
loaded transfersomes using different proportions of Phospholipon(r) 90 G and
Tween(r) 80 (95-75:5-25% w/w). The prepared transfersomes were characterized for
their vesicles size, shape, polydispersity index, zeta potential, entrapment
efficiency, in vitro skin permeation, confocal laser scanning microscopy, and in
vivo skin irritation. Results revealed that the formulated transfersomes were
negatively charged, spherical unilamellar structure of 71.18-85.66 nm with
entrapment efficiency of 83.00-88.19%, and presented transdermal flux of 1.78
5.02 MUg/cm2/h across rat skin. Confocal laser scanning microscopy confirmed that
the formulated rhodamine 6 G loaded transfersomes could penetrate deeply and
uniformly into rat skin. Additionally, in vivo skin irritation studies revealed
that the prepared transfersomes were devoid of any skin irritation potential
(erythema and edema). Results of this study revealed that the transfersomes
prepared with Tween(r) 80 could be used to enhance the transdermal delivery of
eprosartan mesylate. In conclusion, transdermal transfersomes formulation may
prove to be an encouraging drug carrier for eprosartan mesylate and other
actives, particularly owing to their simple formulation and unsophisticated scale
up methods.
PMID- 28504047
TI - Intravascular Ultrasound Validation of Contemporary Angiographic Scores
Evaluating the Severity of Calcification in Peripheral Arteries.
AB - PURPOSE: To validate 3 angiographic scoring systems for peripheral artery
calcification using intravascular ultrasound (IVUS) as the gold standard.
METHODS: The study employed preprocedure angiography and IVUS data from 47
patients (median age 72 years; 34 men) in the 55-patient JetStream G3 Calcium
Study ( ClinicalTrials.gov identifier NCT01273623) to validate the 3 angiographic
scoring systems [Peripheral Academic Research Consortium (PARC), Peripheral
Arterial Calcium Scoring System (PACSS), and the DEFINITIVE Ca++ trial].
Preprocedure angiograms were analyzed using conventional quantitative vessel
analysis software in 2 orthogonal views. Calcium length was evaluated by markers
placed beside the artery during the procedure; calcium deposit(s) were assessed
as being on one or both sides of the vessel wall. The 3 calcium scoring systems
used these 2 basic angiographic elements to evaluate calcium severity. Based on
these criteria, calcium severity varied from none to focal, mild, moderate, or
severe in PARC; grade 0 to 4 in PACSS; and none, moderate, or severe in the
DEFINITIVE Ca++ system. Calcium location on IVUS was classified as superficial,
deep, or mixed. Lesion length was the segment between the most normal looking
proximal and distal reference sites. Superficial, deep, and calcium length were
based on motorized IVUS pullback. RESULTS: IVUS detected calcium in 44/47 (93.6%)
lesions, and angiography detected calcium in 26/47 (55.3%) lesions (p<0.001). The
sensitivity, specificity, positive predictive value, and negative predictive
value of angiography relative to IVUS were 59%, 100%, 100%, and 14%,
respectively. With increasing severity of angiographic calcium, there was a
stepwise increase in the prevalence of IVUS superficial calcium and the maximum
arc and length of superficial calcium. Using PARC criteria, with increasing
severity of calcification, IVUS maximum calcium arc increased from 120 degrees
for none to 305 degrees for severe (p<0.001); the length of calcium increased
from 7 to 68 mm (p<0.001). Though a similar trend was seen in IVUS superficial
calcium, it was not observed in IVUS deep calcium. Similar observations were seen
when using the PACSS and DEFINITIVE Ca++ scoring systems. CONCLUSION: IVUS
confirmed that the PARC, PACSS, and DEFINITIVE Ca++ calcium scoring systems can
be used to classify the degree of calcium in peripheral artery disease,
especially superficial calcium.
PMID- 28504048
TI - The Penn State Heart Assistant: A pilot study of a web-based intervention to
improve self-care of heart failure patients.
AB - The Penn State Heart Assistant, a web-based, tablet computer-accessed, secure
application was developed to conduct a proof of concept test, targeting patient
self-care activities of heart failure patients including daily medication
adherence, weight monitoring, and aerobic activity. Patients (n = 12) used the
tablet computer-accessed program for 30 days-recording their information and
viewing a short educational video. Linear random coefficient models assessed the
relationship between weight and time and exercise and time. Good medication
adherence (66% reporting taking 75% of prescribed medications) was reported.
Group compliance over 30 days for weight and exercise was 84 percent. No
persistent weight gain over 30 days, and some indication of weight loss (slope of
weight vs time was negative (-0.17; p value = 0.002)), as well as increased
exercise (slope of exercise vs time was positive (0.08; p value = 0.04)) was
observed. This study suggests that mobile technology is feasible, acceptable, and
has potential for cost-effective opportunities to manage heart failure patients
safely at home.
PMID- 28504049
TI - Knowing when to hold 'em: regret and the relation between missed opportunities
and risk taking in children, adolescents and adults.
AB - Regret over missed opportunities leads adults to take more risks. Given recent
evidence that the ability to experience regret impacts decisions made by 6-year
olds, and pronounced interest in the antecedents to risk taking in adolescence,
we investigated the age at which a relationship between missed opportunities and
risky decision-making emerges, and whether that relationship changes at different
points in development. Six- and 8-year-olds, adolescents and adults completed a
sequential risky decision-making task on which information about missed
opportunities was available. Children also completed a task designed to measure
their ability to report regret when explicitly prompted to do so. The
relationship between missed opportunities and risky decision-making did not
emerge until 8 years, at which age it was associated with the ability to
explicitly report regret, and was stronger in adults than in adolescents. These
novel results highlight the potential importance of the ability to experience
regret in children and adolescents' risky decision-making.
PMID- 28504050
TI - How long is sufficient for optimal neuroprotection with cerebral cooling after
ischemia in fetal sheep?
AB - The optimal duration of mild "therapeutic" hypothermia for neonates with hypoxic
ischemic encephalopathy is surprisingly unclear. This study assessed the relative
efficacy of cooling for 48 h versus 72 h. Fetal sheep (0.85 gestation) received
sham ischemia (n = 9) or 30 min global cerebral ischemia followed by normothermia
(n = 8) or delayed hypothermia from 3 h to 48 h (n = 8) or 72 h (n = 8). Ischemia
was associated with profound loss of electroencephalogram (EEG) power, neurons in
the cortex and hippocampus, and oligodendrocytes and myelin basic protein
expression in the white matter, with increased Iba-1-positive microglia and
proliferation. Hypothermia for 48 h was associated with improved outcomes
compared to normothermia, but a progressive deterioration of EEG power after
rewarming compared to 72 h of hypothermia, with impaired neuronal survival and
myelin basic protein, and more microglia in the white matter and cortex. These
findings show that head cooling for 48 h is partially neuroprotective, but is
inferior to cooling for 72 h after cerebral ischemia in fetal sheep. The close
association between rewarming at 48 h, subsequent deterioration in EEG power and
increased cortical inflammation strongly suggests that deleterious inflammation
can be reactivated by premature rewarming.
PMID- 28504051
TI - Modeling qRT-PCR dynamics with application to cancer biomarker quantification.
AB - Quantitative reverse transcription polymerase chain reaction (qRT-PCR) is widely
used for molecular diagnostics and evaluating prognosis in cancer. The utility of
mRNA expression biomarkers relies heavily on the accuracy and precision of
quantification, which is still challenging for low abundance transcripts. The
critical step for quantification is accurate estimation of efficiency needed for
computing a relative qRT-PCR expression. We propose a new approach to estimating
qRT-PCR efficiency based on modeling dynamics of polymerase chain reaction
amplification. In contrast, only models for fluorescence intensity as a function
of polymerase chain reaction cycle have been used so far for quantification. The
dynamics of qRT-PCR efficiency is modeled using an ordinary differential equation
model, and the fitted ordinary differential equation model is used to obtain
effective polymerase chain reaction efficiency estimates needed for efficiency
adjusted quantification. The proposed new qRT-PCR efficiency estimates were used
to quantify GUCY2C (Guanylate Cyclase 2C) mRNA expression in the blood of
colorectal cancer patients. Time to recurrence and GUCY2C expression ratios were
analyzed in a joint model for survival and longitudinal outcomes. The joint model
with GUCY2C quantified using the proposed polymerase chain reaction efficiency
estimates provided clinically meaningful results for association between time to
recurrence and longitudinal trends in GUCY2C expression.
PMID- 28504052
TI - Adenosine A2A receptor agonists with potent antiplatelet activity.
AB - Selected adenosine A2A receptor agonists (PSB-15826, PSB-12404, and PSB-16301)
have been evaluated as new antiplatelet agents. In addition, radioligand-binding
studies and receptor-docking experiments were performed in order to explain their
differential biological effects on a molecular level. Among the tested adenosine
derivatives, PSB-15826 was the most potent compound to inhibit platelet
aggregation (EC50 0.32 +/- 0.05 umol/L) and platelet P-selectin cell-surface
localization (EC50 0.062 +/- 0.2 umol/L), and to increase intraplatelets cAMP
levels (EC50 0.24 +/- 0.01 umol/L). The compound was more active than CGS21680
(EC50 0.97+/-0.07 umol/L) and equipotent to NECA (EC50 0.31 +/- 0.05 umol/L) in
platelet aggregation induced by ADP. In contrast to the results from cAMP assays,
Ki values determined in radioligand-binding studies were not predictive of the
A2A agonists' antiplatelet activity. Docking studies revealed the key molecular
determinants of this new family of adenosine A2A receptor agonists: differences
in activities are related to pi-stacking interactions between the ligands and the
residue His264 in the extracellular loop of the adenosine A2A receptor which may
result in increased residence times. In conclusion, these results provide an
improved understanding of the requirements of antiplatelet adenosine A2A receptor
agonists.
PMID- 28504053
TI - Improved antifouling potential of polyether sulfone polymeric membrane containing
silver nanoparticles: self-cleaning membranes.
AB - A new strategy to enhance the antifouling potential of polyether sulfone (PES)
membrane is presented. Chemically synthesized silver nanoparticles (AgNPs) were
used to prepare a mixed-matrix PES membrane by the phase inversion technique.
Primarily, AgNPs synthesis was confirmed by surface plasmon resonance at 410-430
nm using UV-Visible spectroscopy. X-ray diffraction analysis revealed that AgNPs
were crystalline with a diameter of 21 +/- 2 nm. Furthermore, PES membranes were
characterized by energy dispersive X-ray spectroscopy to confirm the
incorporation of AgNPs in membranes. Hydrophilicity of the membranes was
enhanced, whereas roughness, mechanical strength and biofouling were relatively
reduced after embedding the AgNPs. Antibacterial potential of AgNPs was evaluated
for E. coli in the disc diffusion and colony-forming unit (CFU) count method. All
of the membranes were assessed for antifouling activity by filtering a control
dilution (106 CFU/ml) of E. coli and by counting CFU. Anti-biofouling activity of
the membrane was observed with different concentrations of AgNPs. Maximum
reduction (66%) was observed in membrane containing 1.5% of AgNPs. The addition
of antibiotic ceftriaxone enhanced the antibacterial effect of AgNPs in PES
membranes. Our practicable antifouling strategy may be applied to other polymeric
membranes which may pave the new way to achieve sustainable and self-cleaning
membrane reactors on large scale.
PMID- 28504054
TI - Exploring the challenges in obtaining physical activity data from women using hip
worn accelerometers.
AB - Quality objective physical activity data are required to inform physical activity
based health improvement initiatives, however, various challenges undermine
acquisition of such data. We examined the efficacy and challenges of a hip-worn
accelerometry protocol in women. Specific objectives included determining
accelerometer-wear-compliance rates and understanding the barriers and
acceptability of wearing accelerometers. Healthy New Zealand women (n = 406) of
three ethnicities (Maori (indigenous New Zealander), Pacific, European) aged 16
45 years (30.9 +/- 8.7 y) wore hip-mounted Actigraph wGT3X+ accelerometers for 7
consecutive days under a 24-h wear protocol. Post hoc, a sub-sample (n = 45; age:
29.4 +/- 9.0 y) was interviewed to investigate comfort/convenience and burdens of
accelerometer-wear. Wear-compliance (>=10 h/day, >=4 day) was 86%. European women
returned more valid data (92.7%, p < .04) than Pacific (73.0%) or Maori women
(82.1%). Twenty-two participants (5.4%) had completely missing data; 13 due to
lost accelerometers. Burden of accelerometer-wear was greatest during sleeping
(66.7%) due to discomfort. Embarrassment of accelerometer visibility through
clothing and consequent restricted clothing choices caused high burden in social
settings (45.2%). Discomfort during sleeping, embarrassment due to perceived
appearance in social settings and ethnicity are key factors affecting the
efficacy of collecting physical activity data from women using hip-worn
accelerometers. Refining accelerometer design to reduce size and subsequently
participant burden should improve acceptability and wear-compliance. Increasing
overall participant compliance by reducing burden and ensuring appropriate
understanding of study aims and relevance should reduce attrition and improve
wear-compliance and data quality when collecting accelerometry data from women of
different ethnicities.
PMID- 28504056
TI - Corrigendum.
PMID- 28504055
TI - Severe generalised chondrodysplasia in miniature cattle breeds.
PMID- 28504057
TI - Molecular dynamic modeling of CYP51B in complex with azole inhibitors.
AB - Cytochrome P450 14alpha-sterol demethylase (CYP51), the key enzyme in sterol
biosynthesis pathway, is an important target protein of cholesterol-lowering
agents, antifungal drugs, and herbicides. CYP51B enzyme is one of the CYP51
family members. In the present study, we have chosen four representative
inhibitors of CYP51B: diniconazole (Din), fluconazole (Flu), tebuconazole (Teb),
and voriconazole (Vor), and launched to investigate the binding features of
CYP51B-inhibitor and gating characteristics via molecular docking and molecular
dynamics (MD) simulations. The results show that the ranking of binding
affinities among these inhibitors is Din > Teb > Vor > Flu. Din shows the
strongest binding affinity, whereas Flu shows the weakest binding affinity. More
importantly, based on the calculated binding free energy results, we hypothesize
that the nonpolar interactions are the most important contributors, and three key
residues (Thr77, Ala258, and Lys454) play crucial role in protein-inhibitor
binding. Besides, residue Phe180 may play a molecular switch role in the process
of the CYP51B-Teb and CYP51B-Vor binding. Additionally, Tunnel analysis results
show that the major tunnel of Din, Flu, and Teb is located between helix K, FG
loop, and beta4 hairpin (Tunnel II).The top ranked possible tunnel (Tunnel II)
corresponds to Vor exits through helix K, F and helix J. This study further
revealed the CYP51B relevant structural characteristics at the atomic level as
well as provided a basis for rational design of new and more efficacious
antifungal agents.
PMID- 28504058
TI - South Korean anthropometric data and survey methodology: 'Size Korea' project.
AB - Considering the many emerging markets in East Asia, access to contemporary
anthropometric data for this region is important for designers and manufacturers
seeking to produce the best fitting products and living environments for
consumers. The purpose of this paper is to describe Korean anthropometric data
collection and survey techniques for those who are interested in ethnic
characteristics, conducting surveys, and formulating ergonomic product designs
for South Korean and, more broadly, East Asian populations. The Size Korea survey
was conducted in 2003-2004 and 2010. A total of 14,200 civilians aged 0-90 years
participated in the survey, with 119 body and weight dimensions measured in 2004.
Twenty new dimensions from Inbody measurement were added in 2010 and the data
were continuously updated. We referred to ISO 7250, 8559 and 15535 to ensure
validity and reliability. Fifty major body dimensions, including weight, are
summarised in this paper, and 34 of these dimensions can be compared with 11
multinational data already reported in other publications. Practitioner Summary:
This paper presents the up-to-date anthropometric database of East Asian physical
characteristics and survey methodology. These data satisfy the ISO standards and
comprise 50 physical dimensions including weight. Thirty-four dimensions of these
can be directly compared with available multinational data.
PMID- 28504059
TI - Coupled microalgal cultivation with the treatment of domestic sewage and high
level CO2.
AB - The ability of Scenedesmus quadricauda SDEC-13 to accumulate biomass and remove
nutrients in domestic sewage from campus when incorporated with 15% CO2 was
explored. The maximum specific growth rate, biomass productivity, biomass
concentration, and CO2 fixation rate were 0.14 d-1, 0.08 g/L/d, 0.69 g/L, and
0.076 g-CO2/L/d, respectively. The lipid content of SDEC-13 at different culture
phases was also evaluated and it increased following nutrient limitation. The
removal efficiencies of total nitrogen, total phosphorus, nitrate, and ammonium
were all above 90%. A coupled system was designed with hydraulic retention time
of 8.33 d and biomass harvest ratio of 12%, which could yield 0.54 g/L biomass
and 25% lipid content with efficient domestic sewage treatment.
PMID- 28504060
TI - Responding to the support needs of front-line public health nurses who work with
vulnerable families and children: a qualitative study.
AB - BACKGROUND: This paper reports on a research study to inform the development of a
specialist role to support front line public health nurses (PHNs) working with
vulnerable families and at risk children in Ireland. AIMS: This study aimed to
investigate the position of a leading role and explore the implications of such
change. METHODS: Focus group and semi-structured individual interviews were
conducted with ten purposively selected participants in public health nursing,
social work and a non-governmental children's organisation working in
disadvantaged areas in Dublin. RESULTS: Assistant directors of public health
nursing are in a key position to inform decisions regarding the children's
services. CONCLUSION: Access to support and appropriate supervision are
fundamental resource requirements for PHNs who work with vulnerable families and
at risk children. The introduction of a specialist-leading role to support these
PHN's is essential to sustaining best practice.
PMID- 28504063
TI - The 21st Century Cures Act and the Future of Health Education and Health-Related
Behavioral Research.
PMID- 28504062
TI - The Health Promoting Schools Framework: Known Unknowns and an Agenda for Future
Research.
AB - The World Health Organization's Health Promoting Schools (HPS) framework is a
whole-school approach to promoting health that recognizes the intrinsic
relationship between health and education. Our recent Cochrane systematic review
found HPS interventions produced improvements in a number of student health
outcomes. Here we reflect on what this review was not able to tell us: in other
words, what evidence is missing with regard to the HPS approach. Few HPS
interventions engage with schools' "core business" by examining impacts on
educational outcomes. Current evidence is dominated by obesity interventions,
with most studies conducted with children rather than adolescents. Evidence is
lacking for outcomes such as mental or sexual health, substance use, and
violence. Activities to engage families and communities are currently weak and
unlikely to prompt behavioral change. The HPS approach is largely absent in low
income settings, despite its potential in meeting children's basic health needs.
Intervention theories are insufficiently complex, often ignoring upstream
determinants of health. Few studies provide evidence on intervention
sustainability or cost-effectiveness, nor in-depth contextual or process data. We
set out an agenda for future school health promotion research, considering
implications for key stakeholders, namely, national governments, research
funders, academics, and schools.
PMID- 28504065
TI - Lawrence W. Green Paper of the Year Award.
PMID- 28504064
TI - Implications of the 21st Century Cures Act for the Behavioral and Social Sciences
at the National Institutes of Health.
AB - The 21st Century Cures Act provides funding for key initiatives relevant to the
behavioral and social sciences and includes administrative provisions that
facilitate health research and increase the privacy protections of research
participants. At about the same time as the passage of the Act, the National
Institutes of Health Office of Behavioral and Social Sciences Research released
its Strategic Plan 2017-2021, which addresses three scientific priorities: (a)
improve the synergy of basic and applied behavioral and social sciences research;
(b) enhance and promote the research infrastructure, methods, and measures needed
to support a more cumulative and integrated approach to behavioral and social
sciences; and (c) facilitate the adoption of behavioral and social sciences
research findings in health research and in practice. This commentary describes
the implications of the Cures Act on these scientific priorities and on the
behavioral and social sciences more broadly.
PMID- 28504066
TI - The Association of Recreational and Competitive Running With Hip and Knee
Osteoarthritis: A Systematic Review and Meta-analysis.
AB - Study Design Systematic review and meta-analysis. Background Running is a healthy
and popular activity worldwide, but data regarding its association with
osteoarthritis (OA) are conflicting. Objectives To evaluate the association of
hip and knee OA with running and to explore the influence of running intensity on
this association. Methods PubMed, Embase, and Cochrane Library databases were
used to identify studies investigating the occurrence of OA of the hip and/or
knee among runners. A meta-analysis of studies comparing this occurrence between
runners and controls (sedentary, nonrunning individuals) was conducted. Runners
were regarded as "competitive" if they were reported as professional/elite
athletes or participated in international competitions. Recreational runners were
individuals running in a nonprofessional (amateur) context. The prevalence rate
and odds ratio (with 95% confidence interval [CI]) for OA between runners (at
competitive and recreational levels) and controls were calculated. Subgroup
analyses were conducted for OA location (hip or knee), sex, and years of exposure
to running (less or more than 15 years). Results Twenty-five studies (n = 125810
individuals) were included and 17 (n = 114829 individuals) were meta-analyzed.
The overall prevalence of hip and knee OA was 13.3% (95% CI: 11.6%, 15.2%) in
competitive runners, 3.5% (95% CI: 3.4%, 3.6%) in recreational runners, and 10.2%
(95% CI: 9.9%, 10.6%) in controls. The odds ratio for hip and/or knee OA in
competitive runners was higher than that in recreational runners (1.34; 95% CI:
0.97, 1.86 and 0.86; 95% CI: 0.69, 1.07, respectively; controls as reference
group; for difference, P<.001). Exposure to running of less than 15 years was
associated with a lower association with hip and/or knee OA compared with
controls (OR = 0.6; 95% CI: 0.49, 0.73). Conclusion Recreational runners had a
lower occurrence of OA compared with competitive runners and controls. These
results indicated that a more sedentary lifestyle or long exposure to high-volume
and/or high-intensity running are both associated with hip and/or knee OA.
However, it was not possible to determine whether these associations were
causative or confounded by other risk factors, such as previous injury. Level of
Evidence Etiology/harm, level 2a. J Orthop Sports Phys Ther 2017;47(6):373-390.
doi:10.2519/jospt.2017.7137.
PMID- 28504067
TI - Effectiveness of Inclusion of Dry Needling in a Multimodal Therapy Program for
Patellofemoral Pain: A Randomized Parallel-Group Trial.
AB - Study Design Randomized controlled trial. Background Evidence suggests that
multimodal interventions that include exercise therapy may be effective for
patellofemoral pain (PFP); however, no study has investigated the effects of
trigger point (TrP) dry needling (DN) in people with PFP. Objectives To compare
the effects of adding TrP DN to a manual therapy and exercise program on pain,
function, and disability in individuals with PFP. Methods Individuals with PFP (n
= 60) recruited from a public hospital in Valencia, Spain were randomly allocated
to manual therapy and exercises (n = 30) or manual therapy and exercise plus TrP
DN (n = 30). Both groups received the same manual therapy and strengthening
exercise program for 3 sessions (once a week for 3 weeks), and 1 group also
received TrP DN to active TrPs within the vastus medialis and vastus lateralis
muscles. The pain subscale of the Knee injury and Osteoarthritis Outcome Score
(KOOS; 0-100 scale) was used as the primary outcome. Secondary outcomes included
other subscales of the KOOS, the Knee Society Score, the International Knee
Documentation Committee Subjective Knee Evaluation Form (IKDC), and the numeric
pain-rating scale. Patients were assessed at baseline and at 15-day
(posttreatment) and 3-month follow-ups. Analysis was conducted with mixed
analyses of covariance, adjusted for baseline scores. Results At 3 months, 58
subjects (97%) completed the follow-up. No significant between-group differences
(all, P>.391) were observed for any outcome: KOOS pain subscale mean difference,
2.1 (95% confidence interval [CI]: -4.6, 0.4); IKDC mean difference, 2.3 (95% CI:
-0.1, 4.7); knee pain intensity mean difference, 0.3 (95% CI: -0.2, 0.8). Both
groups experienced similar moderate-to-large within-group improvements in all
outcomes (standardized mean differences of 0.6 to 1.1); however, only the KOOS
function in sport and recreation subscale surpassed the prespecified minimum
important change. Conclusion The current clinical trial suggests that the
inclusion of 3 sessions of TrP DN in a manual therapy and exercise program did
not result in improved outcomes for pain and disability in individuals with PFP
at 3-month follow-up. Level of Evidence Therapy, level 1b. Prospectively
registered July 27, 2015 at www.clinicaltrials.gov (NCT02514005). J Orthop Sports
Phys Ther 2017;47(6):392-401. doi:10.2519/jospt.2017.7389.
PMID- 28504069
TI - Population healthcare: the third dimension.
PMID- 28504068
TI - Psychometric Properties of the Deep Muscle Contraction Scale for Assessment of
the Drawing-in Maneuver in Patients With Chronic Nonspecific Low Back Pain.
AB - Study Design A prospective cohort study. Background Motor control dysfunctions
have been commonly reported in patients with chronic nonspecific low back pain
(LBP). Physical therapists need clinical tools with adequate psychometric
properties to assess such patients in clinical practice. The deep muscle
contraction (DMC) scale is a clinical rating scale for assessing patients'
ability to voluntarily contract deep abdominal muscles. Objectives To investigate
the intrarater reliability, floor and ceiling effects, internal and external
responsiveness, and correlation analysis (with ultrasound measures) of the DMC
scale in patients with chronic nonspecific LBP undergoing a lumbar stabilization
exercise program. Methods Sixty-two patients with chronic nonspecific LBP were
included. At baseline, self-report questionnaires were administered to patients
and a trained assessor evaluated abdominal muscle recruitment with the DMC scale
and ultrasound imaging. Four ratios of the change in abdominal muscle thickness
between the resting and contracted states were calculated through the ultrasound
measures. After 1 week, the same ultrasound measures and DMC scale were collected
again for the reliability analysis. The proportions of patients with the lowest
and highest scores on the DMC scale were calculated to investigate floor and
ceiling effects. All patients underwent a lumbar stabilization program,
administered twice a week for 8 weeks. After the treatment period, all measures
were collected again, with the addition of the global perceived effect scale, to
assess the internal and external responsiveness of the measures. Correlation
coefficients between ultrasound ratios and DMC scale total and subscale scores
were also calculated. Results The intrarater reliability of the DMC scale and the
4 ratios of abdominal muscle thickness varied from moderate to excellent. The DMC
scale showed no floor or ceiling effects. Results for internal responsiveness of
the DMC scale showed large effect sizes (2.26; 84% confidence interval [CI]:
2.06, 2.45), whereas the external responsiveness was below the proposed threshold
(area under the curve = 0.54; 95% CI: 0.39, 0.68). Fair and significant
correlations between some ultrasound ratios and DMC subscales were found.
Conclusion The DMC scale was demonstrated to be a reliable tool, with no ceiling
and floor effects, and to detect change in the ability to contract the deep
abdominal muscles after a lumbar stabilization exercise program, but with low
accuracy for estimating patient-perceived clinical outcome. J Orthop Sports Phys
Ther 2017;47(6):432-441. doi:10.2519/jospt.2017.7140.
PMID- 28504072
TI - 'Pragmatic' and 'explanatory' attitudes to randomised trials.
PMID- 28504070
TI - Adverse effects on health and wellbeing of working as a doctor: views of the UK
medical graduates of 1974 and 1977 surveyed in 2014.
AB - Objective To report on any adverse effects on health and wellbeing of working as
a doctor, as described by senior doctors. Design Questionnaires sent in 2014 to
all medical graduates of 1974 and 1977. Participants 3695 UK medical graduates.
Setting United Kingdom. Main outcome measures Statements about adverse effects
upon health, wellbeing and career. Results The aggregated response rate from
contactable doctors was 84.6% (3695/4369). In response to the question 'Do you
feel that working as a doctor has had any adverse effects on your own health or
wellbeing?', 44% of doctors answered 'yes'. More GPs (47%) than hospital doctors
(42%) specified that this was the case. Three-quarters of doctors who answered
'yes' cited 'stress/work-life balance/workload' as an adverse effect, and 45%
mentioned illness. In response to the statement 'The NHS of today is a good
employer when doctors become ill themselves', 28% of doctors agreed, 29% neither
agreed nor disagreed and 43% disagreed. More women doctors (49%) than men doctors
(40%) disagreed with this statement. More general practitioners (49%) disagreed
than hospital doctors (37%). Conclusions Chronic stress and illness, which these
doctors attributed to their work, were widely reported. Although recent changes
may have alleviated some of these issues, there are lessons for the present and
future if the NHS is to ensure that its medical workforce receives the support
which enables current doctors to enjoy a full and satisfying career and to
contribute fully to health service provision in the UK. Older doctors, in
particular, need support to be able to continue successfully in their careers.
PMID- 28504073
TI - Exploring the relationship between mentoring and doctors' health and wellbeing: a
narrative review.
AB - The health and wellbeing of doctors are crucial, both for the individuals
themselves and their ability to deliver optimum patient care. With increased
pressures on healthcare, support mechanisms that attend to doctors' health and
wellbeing may require greater emphasis to safeguard those working in frontline
services. To inform future developments, this systematic narrative review aimed
to identify, explore and map empirical and anecdotal evidence indicating the
relationships between mentoring activities and the health and wellbeing of
doctors. Twelve databases were searched for publications printed between January
2006 and January 2016. Articles were included if they involved doctors'
engagement in mentoring activities and, either health or wellbeing, or the
benefits, barriers or impact of mentoring. The initial search returned 4669
papers, after exclusions a full-text analysis of 37 papers was conducted.
Reference lists and citations of each retrieved paper were also searched.
Thirteen papers were accepted for review. The Business in the Community model was
used as a theoretical framework for analysis. Mentoring influenced collegiate
relationships, networking and aspects of personal wellbeing, such as confidence
and stress management, and was valued by doctors as a specialist support
mechanism. This review contributes to the evidence base concerning mentoring and
doctors' health and wellbeing. However, it highlights that focused research is
required to explore the relationship between mentoring, and health and wellbeing.
PMID- 28504076
TI - Firm findings on doctors' wellbeing.
PMID- 28504077
TI - Routine Shunting During Carotid Endarterectomy in Patients With Acute Watershed
Stroke.
AB - AIM: To evaluate the protective role of routine shunting in patients with acute
watershed stroke (WS) undergoing carotid endarterectomy (CEA). METHODS: A total
of 138 patients with symptomatic carotid stenosis (SCS) who underwent CEA after
acute ischemic stroke from March 2008 to March 2015 were included in this study.
Transient ischemic attacks were excluded. These patients were divided into 2
groups according to the topographic pattern of the stroke on magnetic resonance
imaging: group 1, territorial strokes (TS) caused by emboli of carotid origin,
and group 2, WS caused by a hemodynamic mechanism related to an SCS. Primary end
points were 30-day mortality and postoperative neurological morbidity. The
insertion of a Pruitt carotid shunt was performed systematically. RESULTS: Ninety
(65.2%) patients presented a TS of carotid origin and were included in group 1,
and 48 (34.8%) of the 138 patients had a WS related to an SCS and were included
in group 2. The median time between clinical onset of the cerebral ischemic event
and surgery was 9 days (range: 0-89 days). Postoperative mortality was 0%. Seven
(5.1%) patients had an aggravation of the neurological status during the
postoperative period, of whom 2 presented a complete regression of the symptoms
in less than 1 hour (definitive postoperative neurologic morbidity: 3.6%).
Postoperative neurologic morbidity rate was significantly higher in the TS group
(7 of 90; 7.8%) compared to the WS group (0 of 48; P = .04). No other independent
predictive factor of neurologic morbidity after CEA for an SCS was found.
CONCLUSIONS: Our results suggest that routine shunting should be considered in
case of acute WS since it may play a protective role. Further studies are eagerly
awaited to better define the timing and the best treatment option for both acute
WS and TS related to an SCS in order to reduce postoperative neurologic
morbidity.
PMID- 28504078
TI - A review on therapeutic potentials of Trigonella foenum graecum (fenugreek) and
its chemical constituents in neurological disorders: Complementary roles to its
hypolipidemic, hypoglycemic, and antioxidant potential.
AB - OBJECTIVES: The growing rate of neurological disorders is a major concern in
today's scenario. Today's research is focusing on therapeutic interventions
providing benefits in these disorders. Presently, drugs of natural origin have
gained more interest for the treatment of central nervous system disorders for
their efficacy and less/ no side effects. This review is emphasizing the cited
roles of Trigonella foenum graecum (fenugreek) and its constituents in different
neurological manifestations. METHOD: A review of the literature, relevant to the
role of fenugreek and its major constituents including saponins and alkaloids in
different neurological aspects and in delineating the health benefits, was
conducted. RESULTS: The cited research acknowledged that fenugreek and its
constituents exert positive influence on neurological health. Few studies have
reported the beneficial role of fenugreek and its constituents like trigonelline
in pathological symptoms of Alzheimer's disease. Similarly, other studies
evidenced the neuroprotective, antidepressant, antianxiety as well as modulatory
effect on cognitive functions and Parkinson's disease. DISCUSSION: Large
populations are the sufferers of the neurological disorders, pointing the need
for investigation of such therapeutic interventions which target and delay the
underlying pathological hallmarks and exert positive influence on different
neurological health problems. Hypolipidemic, hypoglycemic, antioxidant, and
immunomodulatory effects of fenugreek and its constituents with their potential
role in various neurological disorders were already reported. In future, it would
be of even greater interest to further develop more effective dosage,
supplementation period, and to evaluate the therapeutic potentials of fenugreek
and its constituents in neurological disorders by exploring underlying cellular
and molecular mechanisms.
PMID- 28504079
TI - A novel nonsense NBEAL2 gene mutation causing severe bleeding in a patient with
gray platelet syndrome.
AB - Gray platelet syndrome (GPS) is a rare, inherited bleeding disorder characterized
by the defect of platelet alpha-granule. Up to date, these are only four studies
identifying NBEAL2 gene correlated with GPS. In the current report, we present a
Chinese GPS patient who had severe bleeding tendency, abnormalities of platelet
functions, and absence of platelet alpha-granules. Genomic DNA sequencing for the
patient identified a nonsense mutation (g.27713C>A) of NBEAL2 gene
(g.NG__031914.1) resulting in a premature protein (p.Glu1726*). In comparison
with the reported patients, we conclude that homozygotes with nonsense or
deletion mutation leading to a premature stop codon exhibit more serious bleeding
problem than those with missense mutations.
PMID- 28504080
TI - Expected p-values in light of an ROC curve analysis applied to optimal multiple
testing procedures.
AB - Many statistical studies report p-values for inferential purposes. In several
scenarios, the stochastic aspect of p-values is neglected, which may contribute
to drawing wrong conclusions in real data experiments. The stochastic nature of p
values makes their use to examine the performance of given testing procedures or
associations between investigated factors to be difficult. We turn our focus on
the modern statistical literature to address the expected p-value (EPV) as a
measure of the performance of decision-making rules. During the course of our
study, we prove that the EPV can be considered in the context of receiver
operating characteristic (ROC) curve analysis, a well-established biostatistical
methodology. The ROC-based framework provides a new and efficient methodology for
investigating and constructing statistical decision-making procedures, including:
(1) evaluation and visualization of properties of the testing mechanisms,
considering, e.g. partial EPVs; (2) developing optimal tests via the minimization
of EPVs; (3) creation of novel methods for optimally combining multiple test
statistics. We demonstrate that the proposed EPV-based approach allows us to
maximize the integrated power of testing algorithms with respect to various
significance levels. In an application, we use the proposed method to construct
the optimal test and analyze a myocardial infarction disease dataset. We outline
the usefulness of the "EPV/ROC" technique for evaluating different decision
making procedures, their constructions and properties with an eye towards
practical applications.
PMID- 28504082
TI - Enhancing the Reproducibility of Research Findings.
PMID- 28504083
TI - Comment on "Drug survival analysis is not a good method for assessing the safety
or effectiveness of systemic therapies in psoriasis".
PMID- 28504084
TI - Dermoscopic Features of Facial Trichilemmoma.
PMID- 28504085
TI - Buried Sutures to Facilitate the Closure of Facial Defects.
PMID- 28504081
TI - Dissecting physical structure of calreticulin, an intrinsically disordered Ca2+
buffering chaperone from endoplasmic reticulum.
AB - Calreticulin (CALR) is a Ca2+ binding multifunctional protein that mostly resides
in the endoplasmic reticulum (ER) and plays a number of important roles in
various physiological and pathological processes. Although the major functions
ascribed to CALR are controlling the Ca2+ homeostasis in ER and acting as a
lectin-like ER chaperon for many glycoproteins, this moonlighting protein can be
found in various cellular compartments where it has many non-ER functions. To
shed more light on the mechanisms underlying polyfunctionality of this
moonlighting protein that can be found in different cellular compartments and
that possesses a wide spectrum of unrelated biological activities, being able to
interact with Ca2+ (and potentially other metal ions), RNA, oligosaccharides, and
numerous proteins, we used a set of experimental and computational tools to
evaluate the intrinsic disorder status of CALR and the role of calcium binding on
structural properties and conformational stability of the full-length CALR and
its isolated P- and C-domains.
PMID- 28504086
TI - Drug-Induced Eruptive Melanocytic Nevi.
PMID- 28504087
TI - Response to the Comment by Van den Reek et al. on Drug Survival Analysis is not a
Good Method for Assessing the Safety or Effectiveness of Systemic Therapies in
Psoriasis.
PMID- 28504088
TI - Greater Detection of Small Caliber Blood Vessels in Port Wine Stain with X Mode
Than With Conventional Doppler: A Pilot Study.
PMID- 28504089
TI - Immunohistochemical expression of interferon-gamma in different types of
granulomatous lesions associated with bovine paratuberculosis.
AB - Animals infected with Mycobacterium avium subsp. paratuberculosis (Map) show a
variety of lesions, from focal forms, seen in subclinical stages to diffuse
lesions in clinical cases. The purpose of this study was to evaluate the local
expression of IFN-gamma by immunohistochemistry in relation with the type of
lesion in naturally Map-infected cows. The number of immunolabelled cells, -the
majority morphologically consistent with lymphocytes-, was higher in focal and
diffuse paucibacillary forms than in diffuse multibacillary lesions, where they
appeared closely related to epithelioid cells. Diffuse multibacillary lesions had
the lowest numbers, but higher than controls, and positive cells were
intermingled among the macrophages. The peripheral IFN-gamma production was
higher in all Map infected cows and a positive correlation was found with the
number of immunolabelled cells in the intestine. The findings of this study show
that IFN-gamma would play a role in the development of the different types of
lesions in paratuberculosis, and also points out the importance of adequate
sampling of lymphoid tissue containing samples when studying the local immune
response in which IFN-gamma expression may be involved, especially in cases where
focal lesions are present.
PMID- 28504090
TI - Wound healing in cutaneous leishmaniasis: A double edged sword of IL-10 and TGF
beta.
AB - Immune responses have a crucial role during the wound healing process in
cutaneous leishmaniasis (CL). However, there are several paradoxes in immunity
against CL. On the one hand, regulatory cytokines interleukin (IL)-10 and
transforming growth factor beta (TGF-beta) increase susceptibility to CL through
suppression of several proinflammatory cytokines that require for defense against
CL. On the other hand, these cytokines play a pivotal role in the acceleration of
wound healing process. This review discusses about the dual role of IL-10 and TGF
beta during the wound healing process and immunity against CL to offer a new
insight about wound healing in CL.
PMID- 28504091
TI - Toll like receptor 4: an important molecule in recognition and induction of
appropriate immune responses against Chlamydia infection.
AB - Chlamydia species are obligate intracellular pathogens causing different
infectious diseases particularly asymptomatic genital infections and are also
responsible for a wide range of complications. Previous studies showed that there
are different immune responses to Chlamydia species and their infections are
limited to some cases. Moreover, Chlamydia species are able to alter immune
responses through modulating the expression of some immune system related
molecules including cytokines. Toll like receptors (TLRs) belonge to pathogen
recognition receptors (PRRs) and play vital roles in recognition of microbes and
stimulation of appropriate immune responses. Therefore, it appears that TLRs may
be considered as important sensors for recognition of Chlamydia and promotion of
immune responses against these bacterial infections. Accordingly, TLR4 detects
several microbial PAMPs such as bacterial lipopolysacharide (LPS) and
subsequently activates transcription from pro-inflammatory cytokines in both
MYD88 and TRIF pathways dependent manner. The purpose of this review is to
provide the recent data about the status and major roles played by TLR4 in
Chlamydia species recognition and promotion of immune responses against these
infections and also the relationship between TLR4 activities and pathogenesis of
Chlamydia infections.
PMID- 28504092
TI - Mycoplasma sp. infection in captive Marcgrave's capuchin monkeys (Sapajus
flavius).
AB - Three species of hemoplasmas are known to infect monkeys, 'Candidatus Mycoplasma
kahanei', 'Candidatus Mycoplasma haemomacaque' and 'Candidatus Mycoplasma aoti'.
Marcgrave's capuchin monkey (Sapajus flavius) is a critically endangered
neotropical primate species of the Brazilian Atlantic Forest, and thus, sustained
efforts are needed to protect the health and well-being of these animals. This
study has aimed to screen 12 captive S. flavius from the State of Paraiba,
northeastern Brazil, for hemoplasma infection. Packed cell volume (PCV) was
measured and a pan-hemoplasma PCR protocol performed. A total of 8/12 (66.6%)
monkeys were positive for the 16S rDNA gene of Mycoplasma sp., showing an
identity of 99% to Mycoplasma sp. previously detected in Sapajus apella and
Sapajus sp. monkeys from the Brazilian Amazon. Further studies should be
conducted in order to elucidate whether this potentially novel Mycoplasma sp. is
able to cause anemia in Sapajus sp. monkeys from Brazil.
PMID- 28504093
TI - Genetic characterization of Staphylococcus aureus isolated from nasal samples of
healthy ewes in Tunisia. High prevalence of CC130 and CC522 lineages.
AB - Staphylococcus aureus is a versatile bacterium, which can infect or colonize a
variety of host species. The objective of this study was to characterize S.
aureus isolates recovered from nasal swabs of 167 healthy ewes sampled from 12
farms in different areas of Tunisia during the period of 2014-2015. Genetic
lineages, virulence factors and antibiotic resistance mechanisms were determined
for recovered isolates. S. aureus was detected in 45 out of 167 tested samples
(26.9%). All isolates were methicillin-susceptible (MSSA) and the majority of
them were susceptible to tested antibiotics with few exceptions (% of
resistance): penicillin (8.8), ciprofloxacin (4.4), and tobramycin or
tetracycline (2.2, each). Twelve different spa types were detected (t15098,
t15099, t1773, t3576, t1534, t5428, t3750, t5970 t254, t2883, t127 and t933), two
of them were new (t15098 and t15099). S. aureus isolates were ascribed to agrI
(n=23), agrII (n=1) and agrIII (n=20), and one was non-typeable. According to the
sequence-type (ST) determined and/or the spa-type detected, the 45S. aureus
isolates were assigned to six clonal complexes, with CC522 (44.4%) and CC130
(37.7%) being the most common lineages. Twenty-one (46.6%) and two (4.2%)
isolates harbored the tst and eta genes encoding TSST-1 and ETA, respectively. In
conclusion, nares of healthy ewes could be a reservoir of MSSA CC522 and CC130,
lineages associated with TSST-1 and ETA that might represent a risk to human
health.
PMID- 28504094
TI - Antimicrobial activity of red-tailed phascogale (Phascogale calura) serum.
AB - Antimicrobial substances in serum include circulating complement proteins and
acute phase proteins (APPs). We identified gene sequences for APPs, haptoglobin
(Hp), C-reactive protein (CRP) and serum amyloid A (SAA) in marsupial genomes. Hp
and SAA levels were measured in red-tailed phascogale (Phascogale calura) sera
using commercially available assays. Hp levels were higher in males than females,
while SAA levels suggest the phascogales used in this study were healthy. Serum
was co-cultured with four bacterial species. Bacterial growth was inhibited after
incubation at 37 degrees C, however effectiveness differed with bacteria and
incubation time. The least amount of bacterial growth was noticed after
introduction to K. pneumoniae, and most when introduced to P. aeruginosa. Despite
marsupials not having mature immune tissues at birth, and unable to mount
specific immune responses, this study suggests other immune strategies, such as
APPs in serum likely aid marsupials in their defence against pathogens.
PMID- 28504095
TI - Characterization of porcine Trueperella pyogenes by matrix-assisted laser
desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), molecular
typing and antimicrobial susceptibility profiling in Sao Paulo State.
AB - Trueperella pyogenes can be found as a commensal or pathogenic bacterium among
animals causing a variety of pyogenic infections in several species. The agent
appears to act primarily as an opportunistic pathogen but may disseminate and
produce metastatic abscesses accompanied or not by mastitis, metritis or
pneumonia. In this study, 30 porcine T. pyogenes strains were identified by MALDI
TOF MS and 16S rRNA sequencing and further evaluated in relation to their
resistance and genetic profiles through broth microdilution and single enzyme
AFLP. All strains were susceptible to beta-lactams, florfenicol, gentamicin,
spectinomycin and tiamulin. The highest resistance rates were observed for
sulfonamides, tetracyclines and clindamycin. All isolates could be characterized
by SE-AFLP presenting more than 80% of similarity, despite their distinct
origins. Four genotypes were detected with the segregation of T. pyogenes ATCC
19411 from Brazilian T. pyogenes strains. No correlation between genotypes and
isolates origins and susceptibility profile was observed.
PMID- 28504096
TI - Multiple clones and low antimicrobial resistance rates for Salmonella enterica
serovar Infantis populations in Greece.
AB - All the Salmonella enterica ser. Infantis strains isolated under official control
programs in Greece during a four year period were studied, 23 of human origin, 16
from food animals and one from food. Molecular analyses (PFGE) in combination
with antimicrobial susceptibility testing were used to study whether the
occurrence S. Infantis in Greece resulted from different biotypes or a successful
spread of one clone. Low rates of antimicrobial resistance were observed, except
for streptomycin among human isolates (48%), indicating that selective pressure
due to consumption of antimicrobials has not resulted the spread of dominant
clones. Pulsed Field Gel Electrophoresis revealed 31 XbaI distinct pulsotypes
among the 40 strains with 60% overall similarity reflecting diversity. Four main
clusters were constructed, using an 85% cut off value, clusters A, B, C and D
consisting of 14, 6, 8 and 8 isolates respectively. Point source of transmission
was not hypothesized as multiple reservoirs of the serovar seem to be present in
Greece during the study period.
PMID- 28504097
TI - Humoral immune responses of experimentally Eimeria ninakholyakimovae-infected
goat kids.
AB - Although cellular immune reactions seem to be crucial for protective immune
responses in Eimeria spp. infections, there are also evidences on an active
involvement of the humoral counterpart. In the present study, we have analyzed
the humoral response of goat kids subjected to primary and challenge infections
with Eimeria ninakholyakimovae. Specific levels of IgG and IgM in serum samples
and IgA in the ileal mucus were estimated. In infected kids, significantly
increased levels of IgG were observed from 3 weeks post infection onwards in
addition to an enhancement of specific IgM and secretory IgA levels. A wide range
of peptides of sporulated oocyst antigen (SOA) was recognized by specific IgG as
determined by immunoblotting. However, no correlations were found between
immunoglobulin levels and OPG counts after challenge infection. Overall, these
data indicate a significant specific humoral response of E. ninakohlyakimovae
infected goat kids that does not seem to convey immunoprotection. Further studies
should be addressed to clarify if the lack of correlation might be associated to
the type of antigen used for the immunoenzimatic assays, the age of the animals
or other factors.
PMID- 28504098
TI - First molecular detection of Dirofilaria immitis (Spirurida: Onchocercidae)
infection in dogs from Northern Algeria.
AB - Dirofilaria immitis and Dirofilaria repens are mosquito-borne filarioid nematodes
that affect dogs and other domestic and wild carnivores, causing heartworm
disease and subcutaneous dirofilariosis, respectively. In Algeria, the data about
the epidemiology of these infections is largely unknown. The present study was
designed to establish the occurrence of D. immitis and D. repens in dogs in
Algeria using molecular tools. In 2014 and 2015, a total of 209 dogs over one
year of age of different breed and sex, living in Northern Algeria, were examined
and blood samples were collected from each dog. The presence of D. immitis and D.
repens in these samples was detected by real-time PCR followed by standard PCR
and sequencing. Overall, the blood of 209 dogs from two departments was collected
and only 3 (1.4%) of the blood samples were found positive for D. immitis DNA.
Sequencing of the corresponding amplicon displayed a 99.8% identity to D.
immitis, confirming the presence of this mosquito-borne nematode in Algeria.
Furthermore, all tested samples were negative for D. repens.
PMID- 28504099
TI - Zoonotic intestinal parasites and vector-borne pathogens in Italian shelter and
kennel dogs.
AB - This study investigated the presence of zoonotic parasites and vector-borne
pathogens in dogs housed in kennels and shelters from four sites of Italy. A
total of 150 adoptable dogs was examined with different microscopic, serological
and molecular methods. Overall 129 dogs (86%) were positive for one or more
parasites and/or pathogens transmitted by ectoparasites. Forty-eight (32%) were
positive for one infection, while 81 (54%) for more than one pathogen. The most
common zoonotic helminths recorded were hookworms, roundworms and Capillaria
aerophila, followed by mosquito-borne Dirofilaria spp. and Dipylidium caninum.
One hundred and thirteen (77.9%), 6 (4.1%) and 2 (1.4%) dogs were positive for
Rickettsia spp., Leishmania infantum and Anaplasma spp., respectively. The
results show that dogs living in rescue facilities from the studied areas may be
infected by many zoonotic internal parasites and vector-borne pathogens, and that
control measures should be implemented.
PMID- 28504101
TI - Prepublication and clinical practice: challenges ahead.
PMID- 28504100
TI - Ectonucleotidase and adenosine deaminase as inflammatory marker in dairy cows
naturally infected by Dictyocaulus viviparus.
AB - The aim of this study was to evaluate the influence of dictyocaulosis (mild or
severe) on enzymes of NTPDase, 5'-nucleotidase, and adenosine deaminase (ADA) of
dairy cows naturally infected by Dictyocaulus viviparus. Blood and faeces were
collected from 22 dairy cows of the same farm to evaluate NTPDase (ATP and ADP
substrate), 5'-nucleotidase, and ADA activities on days 0 (pre-treatment) and 10
(post-treatment). Seric activities of NTPDase (ATP substrate), 5'-nucleotidase,
and ADA were lower (P<0.05) in D. viviparus infected animals compared to
uninfected cows. The number of D. viviparus larvae per gram of faeces varied
among the animals, and they showed different degrees of severity according to
respiratory clinical signs of the disease (cough and nasal discharge). Later,
these cows were divided into two groups: those with mild (n=10) and severe (n=12)
disease. Cows with severe disease showed higher NTPDase activity (ATP substrate)
than those with mild disease (P<=0.05). The opposite occurred with NTPDase (ADP
substrate), 5'-nucleotidase, and ADA in cows with severe disease, that is, the
enzymatic activity of these seric enzymes significantly decreased (P<=0.05)
compared to animals with mild disease. Infected animals showed reduced NTPDase
activity (ATP and ADP substrate) after treatment. No enzymatic changes were
observed for 5'-nucleotidase, and ADA pre- and post-treatment (P>0.05). Based on
these results, we conclude that dictyocaulosis alters NTPDase, 5'-nucleotidase,
and ADA activities of cow naturally infected by the parasite, in consequence the
enzymes act as inflammatory markers.
PMID- 28504102
TI - The neurodegenerative prodrome in multiple sclerosis.
PMID- 28504103
TI - Detection of neurodegenerative disease using olfaction.
PMID- 28504104
TI - The multiple faces of artwork diagnoses.
PMID- 28504105
TI - The multiple faces of artwork diagnoses.
PMID- 28504106
TI - The multiple faces of artwork diagnoses.
PMID- 28504107
TI - Jorge Sepulcre.
PMID- 28504108
TI - Tuberculous meningitis and hydrocephalus in Filippino de' Medici.
PMID- 28504109
TI - Severe traumatic brain injury: targeted management in the intensive care unit.
AB - Severe traumatic brain injury (TBI) is currently managed in the intensive care
unit with a combined medical-surgical approach. Treatment aims to prevent
additional brain damage and to optimise conditions for brain recovery. TBI is
typically considered and treated as one pathological entity, although in fact it
is a syndrome comprising a range of lesions that can require different therapies
and physiological goals. Owing to advances in monitoring and imaging, there is
now the potential to identify specific mechanisms of brain damage and to better
target treatment to individuals or subsets of patients. Targeted treatment is
especially relevant for elderly people-who now represent an increasing proportion
of patients with TBI-as preinjury comorbidities and their therapies demand
tailored management strategies. Progress in monitoring and in understanding
pathophysiological mechanisms of TBI could change current management in the
intensive care unit, enabling targeted interventions that could ultimately
improve outcomes.
PMID- 28504111
TI - Olfactory dysfunction in neurodegenerative diseases: is there a common
pathological substrate?
AB - In patients with neurodegenerative diseases, there is a spectrum of smell
dysfunction ranging from severe loss, as seen in Alzheimer's disease and
Parkinson's disease, to relatively little loss, as seen in progressive
supranuclear palsy. Given the ubiquitous but varying degrees of olfactory
dysfunction among such diseases, it is conceivable that differential disruption
of a common primordial neuropathological substrate causes these differences in
olfactory function. For example, the amount of damage to forebrain
neurotransmitter and neuromodulator circuits, most notably those involving
cholinergic transmission, appears to be correlated with quantitative smell test
scores across a wide range of neurodegenerative diseases. Thus, a key question is
whether damage to such a substrate is the basis for the perceptual differences in
olfaction or whether disease-specific or other entities, such as respiratory
infections or pollution, are responsible. In light of the early preclinical onset
of smell deficits in many neurodegenerative diseases, the answer to this question
might provide crucial insight into the cause of disease pathology at its earliest
stages of development.
PMID- 28504110
TI - Neurological consequences of obesity.
AB - The high prevalence of obesity is associated with an enormous medical, social,
and economic burden. The metabolic dysfunction, dyslipidaemia, and inflammation
caused by obesity contribute to the development of a wide variety of disorders
and effects on the nervous system. In the CNS, mild cognitive impairment can be
attributed to obesity-induced alterations in hippocampal structure and function
in some patients. Likewise, compromised hypothalamic function and subsequent
defects in maintaining whole-body energy balance might be early events that
contribute to weight gain and obesity development. In the peripheral nervous
system, obesity-driven alterations in the autonomic nervous system prompt
imbalances in sympathetic-parasympathetic activity, while alterations in the
sensory-somatic nervous system underlie peripheral polyneuropathy, a common
complication of diabetes. Pharmacotherapy and bariatric surgery are promising
interventions for people with obesity that can improve neurological function.
However, lifestyle interventions via dietary changes and exercise are the
preferred approach to combat obesity and reduce its associated health risks.
PMID- 28504112
TI - Potential impact of a volume pledge on spatial access: A population-level
analysis of patients undergoing pancreatectomy.
AB - BACKGROUND: A minimum-volume policy restricting hospitals not meeting the
threshold from performing complex operation may increase travel burden and
decrease spatial access to operation. We aim to identify vulnerable populations
that would be sensitive to an added travel burden. METHODS: We performed a
retrospective analysis of the database of the California Office of Statewide
Health Planning and Development for patients undergoing pancreatectomy from 2005
to 2014. Number of hospitals bypassed was used as a metric for travel. Patients
bypassing fewer hospitals were deemed to be more sensitive to an added travel
burden. RESULTS: There were 13,374 patients who underwent a pancreatectomy, of
whom 2,368 (17.7%) were nonbypassers. On unadjusted analysis, patients >80 year
old travelled less than their younger counterparts, bypassing a mean of 10.9 +/-
9.5 hospitals compared with 14.2 +/- 21.3 hospitals bypassed by the 35-49 year
old age group (P < .001). Racial minorities travelled less when compared with non
Hispanic whites (P < .001). Patients identifying their payer status as self-pay
(8.9 +/- 15.6 hospitals bypassed) and Medicaid (10.1 +/- 17.2 hospitals bypassed)
also travelled less when compared with patients with private insurance (13.8 +/-
20.4 hospitals bypassed, P < .001). On multivariate analysis, advanced age,
racial minority, and patients with self-pay or Medicaid payer status were
associated independently with increased sensitivity to an added travel burden.
CONCLUSION: In patients undergoing pancreatectomy, the elderly, racial
minorities, and patients with self-pay or Medicaid payer status were associated
with an increased sensitivity to an added travel burden. This vulnerable cohort
may be affected disproportionately by a minimum-volume policy.
PMID- 28504113
TI - Prognosis of spontaneous coronary artery dissection treated by percutaneous
coronary intervention with optical coherence tomography.
AB - BACKGROUND: Although about half of patients with spontaneous coronary artery
dissection (SCAD) face ongoing necrosis, conservative therapy is recommended due
to a high complication rate in angiography-guided percutaneous coronary
intervention (PCI). The aim of this study was to investigate clinical outcomes of
SCAD treated by optical coherence tomography (OCT)-guided PCI. METHODS: This
study consisted of consecutive 306 patients with acute coronary syndrome (ACS)
who underwent OCT-guided PCI. Based on the culprit lesion morphology by OCT,
patients were assigned to four groups: a SCAD group, a plaque rupture (PR) group,
a calcified nodule (CN) group, and an undetermined etiology (UE) group.
Successful PCI was defined as thrombolysis in myocardial infarction flow grade 3
in final angiography without any complications. Primary endpoint was defined as
occurrence rate of major adverse cardiac events (MACE) including cardiac death,
myocardial infarction, and unstable angina pectoris. RESULTS: OCT revealed 12
SCADs, 149 PRs, 16 CNs, and 129 UEs, respectively. No significant difference was
observed in the success rate of PCI (SCAD 91.7%, PR 85.2%, CN 81.2%, UE 86.8%,
p=0.88), while wire repositioning was needed in 2 SCAD cases (p<0.01). The mean
follow-up periods were 17.1+/-13.3 months. No significant difference was observed
in MACE among the groups (p=0.56). CONCLUSIONS: The clinical outcomes of OCT
guided PCI for SCAD were favorable, as well as those for other ACS etiologies.
OCT-guided PCI could become a therapeutic option for SCAD compromised with
ongoing necrosis.
PMID- 28504114
TI - A shortened tamoxifen induction scheme to induce CreER recombinase without side
effects on the male mouse skeleton.
AB - The selective estrogen receptor modulator tamoxifen exerts estrogen agonistic or
antagonistic actions on several tissues, including bone. The off-target effects
of tamoxifen are one of the most widely recognized pitfalls of tamoxifen
inducible Cre recombinases (CreERs), potentially confounding the phenotypic
findings. Still, the validation of tamoxifen induction schemes that minimize the
side effects of the drug has not been addressed. Here, we compared the side
effects on the skeleton and other androgen-responsive targets of a shortened
tamoxifen regimen (2 doses of 190 mg/kg body weight by oral gavage) to a standard
protocol (4 doses) and determined their efficiency in inducing CreER-mediated
gene deletion. In addition, both a vehicle- and a 10-dose group, which served as
a positive control for tamoxifen side effects, were also included. For this
purpose, we generated male mice with a floxed androgen receptor (AR) and a neuron
specifically expressed CreER. Treatment with two doses of tamoxifen was the only
regimen that did not diminish androgenic bioactivity, as assessed by both seminal
vesicles and levator ani/bulbocavernosus muscle weights and serum testosterone
concentrations. Similarly, trabecular and cortical femoral bone structure were
dramatically altered by both the standard and high-dose protocols but not by the
shortened version. Serum osteocalcin and bone-gene expression analyses confirmed
the absence of effects on bone by 2 doses of tamoxifen. This protocol decreased
AR mRNA levels efficiently and specifically in the nervous system. Thus, we
optimized a protocol for tamoxifen-induced CreER gene deletion in mice without
off-target effects on bone and male reproductive organs.
PMID- 28504115
TI - Protocatechuic acid inhibits hepatitis B virus replication by activating ERK1/2
pathway and down-regulating HNF4alpha and HNF1alpha in vitro.
AB - AIMS: Protocatechuic acid (PCA) is a phenolic compound found in many antiviral
Chinese herbal medicines. HNF4alpha and HNF1alpha, the members of hepatocyte
nuclear factor (HNF) family, play an important regulatory role in the gene
transcription of hepatitis B virus (HBV). Previous studies found that PCA
inhibited HBV antigen secretion and HBV DNA replication in HepG2.2.15 cells, but
its anti-HBV mechanism has not been fully understood. We aim to illustrate the
anti-HBV mechanism of PCA. MATERIALS AND METHODS: MTT was used to estimate
cytotoxicity. The content of HBsAg or HBeAg was detected using an enzyme-linked
immunosorbent assay kit. HBV DNA in cell-free culture media was detected by PCR
kit. HNF1alpha and HNF4alpha mRNA expression was detected by real-time PCR.
HNF1alpha, HNF4alpha and ERK1/2 protein expression was detected by western
blotting and HBV promoter activity was tested by luciferase reporter assay. KEY
FINDINGS: Our results demonstrated that PCA inhibited the gene transcription and
protein translation of HNF1alpha and HNF4alpha in Huh7 and HepG2.2.15 cells, as
well as the promoter activities of HBV X and preS1 in Huh7 cells transfected with
the luciferase reporter plasmid of HBV promoter. Further study suggested that PCA
induced the phosphorylation of extracellular-signal-related kinase (ERK) 1/2, and
thereby inhibited HNF4alpha and HNF1alpha expression in HepG2.2.15 cells to exert
its antiviral activity. SIGNIFICANCE: To our knowledge, this study is the first
to reveal the anti-HBV mechanism of PCA. Our results demonstrate that PCA
inhibits HBV replication by activating ERK1/2 pathway and subsequently down
regulating HNF4alpha and HNF1alpha in HepG2.2.15 cells.
PMID- 28504116
TI - Exercise reverses pain-related weight asymmetry and differentially modulates
trabecular bone microarchitecture in a rat model of osteoarthritis.
AB - : There is great interest in developing and utilizing non-pharmacological/non
invasive forms of therapy for osteoarthritis (OA) pain including exercise and
other physical fitness regimens. AIMS: The present experiments determined the
effects of prior wheel running on OA-induced weight asymmetry and trabecular bone
microarchitecture. MAIN METHODS: Wheel running included 7 or 21days of prior
voluntary access to wheels followed by OA induction, followed by 21days post-OA
access to wheels. OA was induced with monosodium iodoacetate (MIA), and weight
asymmetry was measured using a hind limb weight bearing apparatus. Bone
microarchitecture was characterized using ex vivo MUCT. KEY FINDINGS: Relative to
saline controls, MIA (3.2mg/25MUl) produced significant weight asymmetry measured
on post-days (PDs) 3, 7, 14, 21 in sedentary rats. Seven days of prior running
failed to alter MIA-induced weight asymmetry. In contrast, 21days of prior
running resulted in complete reversal of MIA-induced weight asymmetry on all days
tested. As a comparator, the opioid agonist morphine (3.2-10mg/kg) dose
dependently reversed weight asymmetry on PDs 3, 7, 14, but was ineffective in
later-stage (PD 21) OA. In runners, Cohen's d (effect sizes) for OA vs. controls
indicated large increases in bone volume fraction, trabecular number, trabecular
thickness, and connective density in lateral compartment, and large decreases in
the same parameters in medial compartment. In contrast, effect sizes were small
to moderate for sedentary OA vs. CONTROLS: SIGNIFICANCE: Results indicate that
voluntary exercise may protect against OA pain, the effect varies as a function
of prior exercise duration, and is associated with distinct trabecular bone
modifications.
PMID- 28504118
TI - Direct evidence of central nervous system axonal damage in patients with
postoperative delirium: A preliminary study of pNF-H as a promising serum
biomarker.
AB - INTRODUCTION: Approximately 50-80% patients experience postoperative delirium, an
acute cognitive dysfunction associated with prolonged hospitalization, increased
mortality, excess healthcare costs, and persistent cognitive impairment.
Elucidation of the mechanism of delirium and associated diagnostic and
therapeutic measures are urgently required. Here we investigated the role of
phosphorylated neurofilament heavy subunit (pNF-H), a major structural protein in
axons, as a predictive maker of postoperative delirium. MATERIAL AND METHODS:
Twenty-three patients who underwent surgery for abdominal cancer were screened
for postoperative delirium, and they were assessed for its severity using the
memorial delirium assessment scale (MDAS) at and 48h after delirium onset. Serum
pNF-H levels were also measured at both time points. The patients were divided
into two groups according to the presence or absence of pNF-H. Clinical variables
were compared between groups using the Mann-Whitney U test, and the relationship
between pNF-H levels and delirium severity was analyzed using the exponential
curve fitting. RESULTS: Fifteen of the 23 (65.2%) patients tested positive for
pNF-H, and these patients exhibited significantly higher MDAS scores compared
with the pNF-H-negative patients only at the onset of delirium. Although the MDAS
score significantly improved over time in the positive group, pNF-H positivity
persisted. There was a correlation between the maximum pNF-H level and maximum
MDAS score (R2=0.31, p=0.013). CONCLUSIONS: More severe postoperative delirium
was directly related to higher serum pNF-H levels, suggesting the potential
application of pNF-H as a quantitative biomarker of neural damage in
postoperative delirium.
PMID- 28504117
TI - Surround Integration Organizes a Spatial Map during Active Sensation.
AB - During active sensation, sensors scan space in order to generate a representation
of the outside world. However, since spatial coding in sensory systems is
typically addressed by measuring receptive fields in a fixed, sensor-based
coordinate frame, the cortical representation of scanned space is poorly
understood. To address this question, we probed spatial coding in the rodent
whisker system using a combination of two-photon imaging and electrophysiology
during active touch. We found that surround whiskers powerfully transform the
cortical representation of scanned space. On the single-neuron level, surround
input profoundly alters response amplitude and modulates spatial preference in
the cortex. On the population level, surround input organizes the spatial
preference of neurons into a continuous map of the space swept out by the
whiskers. These data demonstrate how spatial summation over a moving sensor array
is critical to generating population codes of sensory space.
PMID- 28504119
TI - The ratio of 1/3 linoleic acid to alpha linolenic acid is optimal for
oligodendrogenesis of embryonic neural stem cells.
AB - During neural development, embryonic neural stem cells (eNSCs) differentiate
toward glial, oligodendrocytic, and neuronal cells. Dysregulation of
polyunsaturated fatty acids (PUFAs) induce a wide range of neurological and
developmental disorders. In this study, we investigated the effect of various
concentrations and ratios of linoleic acid (LA) and alpha linolenic acid (ALA),
which belong respectively to omega-6 and omega-3 PUFAs, on the proliferation and
differentiation of eNSCs.Results showed that low (25 and 50MUM) or high (100 and
200MUM) concentrations of ALA, but not LA, and the ratio of 1:3 of LA/ALA
significantly increased neurospheres size, frequency and cell numbers, in
comparison to controls. Moreover, low or high concentrations of ALA, but not LA,
and different ratios of LA/ALA resulted in a significant increase in mRNA
expression levels of Notch1, Hes1 and Ki-67, and the differentiation of eNSCs
toward astrocytes (GFAP) and oligodendrocytes (MBP), but not neurons (beta-III
Tubulin), with the highest increase being for LA/ALA ratio of 1:3, in comparison
to controls. These results demonstrate the importance of higher concentrations of
ALA in enhancing proliferation and differentiation of eNSCs, which could be used
in diet to help preventing neurodevelopmental syndromes, cognitive decline during
aging, and various psychiatric disorders.
PMID- 28504120
TI - Mismatch negativity (MMN) to speech sounds is modulated systematically by manual
grip execution.
AB - Manual actions and speech are connected: for example, grip execution can
influence simultaneous vocalizations and vice versa. Our previous studies show
that the consonant [k] is associated with the power grip and the consonant [t]
with the precision grip. Here we studied whether the interaction between speech
sounds and grips could operate already at a pre-attentive stage of auditory
processing, reflected by the mismatch-negativity (MMN) component of the event
related potential (ERP). Participants executed power and precision grips
according to visual cues while listening to syllable sequences consisting of [ke]
and [te] utterances. The grips modulated the MMN amplitudes to these syllables in
a systematic manner so that when the deviant was [ke], the MMN response was
larger with a precision grip than with a power grip. There was a converse trend
when the deviant was [te]. These results suggest that manual gestures and speech
can interact already at a pre-attentive processing level of auditory perception,
and show, for the first time that manual actions can systematically modulate the
MMN.
PMID- 28504121
TI - Corticospinal excitability during the processing of handwritten and typed words
and non-words.
AB - A number of studies have suggested that perception of actions is accompanied by
motor simulation of those actions. To further explore this proposal, we applied
Transcranial magnetic stimulation (TMS) to the left primary motor cortex during
the observation of handwritten and typed language stimuli, including words and
non-word consonant clusters. We recorded motor-evoked potentials (MEPs) from the
right first dorsal interosseous (FDI) muscle to measure cortico-spinal
excitability during written text perception. We observed a facilitation in MEPs
for handwritten stimuli, regardless of whether the stimuli were words or non
words, suggesting potential motor simulation during observation. We did not
observe a similar facilitation for the typed stimuli, suggesting that motor
simulation was not occurring during observation of typed text. By demonstrating
potential simulation of written language text during observation, these findings
add to a growing literature suggesting that the motor system plays a strong role
in the perception of written language.
PMID- 28504122
TI - GABAB receptors and pain.
AB - Over the past three decades the research on GABAB receptor biology and
pharmacology in pain processing has been a fascinating experience. Norman
Bowery's fundamental discovery of the existence of the GABAB receptor has led the
way to the definition of GABAB molecular mechanisms; patterns of receptor
expression in the peripheral and central nervous system; GABAB modulatory
functions within the pain pathways. We are now harnessing this acquired knowledge
to develop innovative approaches to the therapeutic management of chronic pain
through allosteric modulation of the GABAB. Norman's legacy would be ultimately
fulfilled by the development of novel analgesics that activate the GABAB
receptor. This article is part of the "Special Issue Dedicated to Norman G.
Bowery".
PMID- 28504123
TI - Erythropoietin and small molecule agonists of the tissue-protective
erythropoietin receptor increase FXN expression in neuronal cells in vitro and in
Fxn-deficient KIKO mice in vivo.
AB - Friedreich's ataxia (FA) is a progressive neurodegenerative disease caused by
reduced levels of the mitochondrial protein frataxin (FXN). Recombinant human
erythropoietin (rhEPO) increased FXN protein in vitro and in early clinical
studies, while no published reports evaluate rhEPO in animal models of FA. STS
E412 and STS-E424 are novel small molecule agonists of the tissue-protective, but
not the erythropoietic EPO receptor. We find that rhEPO, STS-E412 and STS-E424
increase FXN expression in vitro and in vivo. RhEPO, STS-E412 and STS-E424
increase FXN by up to 2-fold in primary human cortical cells and in retinoic-acid
differentiated murine P19 cells. In primary human cortical cells, the increase in
FXN protein was accompanied by an increase in FXN mRNA, detectable within 4 h.
RhEPO and low nanomolar concentrations of STS-E412 and STS-E424 also increase FXN
in normal and FA patient-derived PBMC by 20%-40% within 24 h, an effect that was
comparable to that by HDAC inhibitor 4b. In vivo, STS-E412 increased Fxn mRNA and
protein in wild-type C57BL6/j mice. RhEPO, STS-E412, and STS-E424 increase FXN
expression in the heart of FXN-deficient KIKO mice. In contrast, FXN expression
in the brains of KIKO mice increased following treatment with STS-E412 and STS
E424, but not following treatment with rhEPO. Unexpectedly, rhEPO-treated KIKO
mice developed severe splenomegaly, while no splenomegaly was observed in STS
E412- or STS-E424-treated mice. RhEPO, STS-E412 and STS-E424 upregulate FXN
expression in vitro at equal efficacy, however, the effects of the small
molecules on FXN expression in the CNS are superior to rhEPO in vivo.
PMID- 28504124
TI - Structural characterization and rheological properties of a gel-like beta-d
glucan from Pholiota nameko.
AB - A crude fraction (SCW) was extracted with cold water from Pholiota nameko and
showed mannose (24.1%), galactose (44.9%) and glucose (31%). Purification
procedures resulted in a polysaccharide fraction (bG-PN), that showed only
glucose. NMR and methylation analyses of bG-PN indicated a beta-d-glucan-(1->3)
linked, substituted at O-6 by beta-d-Glcp or (1->6)-linked beta-d-Glcp side
chains. Rheological studies of crude and purified fractions at the same
concentration showed similar shear-thinning behavior and gel-like structure which
indicates no need to isolate the polymer to achieve some desirable rheological
properties. SCW (at 1% and 2%) and bG-PN (at 2%) presented thermal stability
during heating and cooling, suggesting that the physical structure of gels (SCW
and bG-PN at 2%) and viscoelastic fluid (SCW at 1%) formed were not altered in
the tested temperature range. Our results suggest that P. nameko beta-d-glucans
can be applied in different food preparations as thickener or gelling agents
modifying their rheological properties.
PMID- 28504125
TI - Preparation of chitosan-TiO2 composite film with efficient antimicrobial
activities under visible light for food packaging applications.
AB - By incorporation of TiO2 nano-powder in chitosan, a chitosan-TiO2 composite film
was prepared with efficient antimicrobial activity against food-borne pathogenic
microbes and expected to be a promising food packaging material. Scanning
electron microscopy analysis showed that the TiO2 nano-powder was successfully
and uniformly dispersed into the chitosan matrix. TiO2 addition led to enhanced
hydrophilicity, to better mechanical properties, and to decreased light
transmittance in visible light region of the composite film. The chitosan-TiO2
film possessed efficient antimicrobial activity against four tested strains, i.e.
Escherichia coli, Staphylococcus aureus, Candida albicans, and Aspergillus niger
with 100% sterilization in 12h. It moreover provoked the leakage of cellular
substances through damaged membrane. The prepared chitosan-TiO2 film was tested
for packaging red grapes to prevent microbial infection and extend their shelf
life. Results were positive, stressing the potential of the novel bio-nano
composite film for food packaging applications.
PMID- 28504126
TI - Chemical modification of nanocellulose with canola oil fatty acid methyl ester.
AB - Cellulose nanocrystals (CNCs), produced from dissolving wood pulp, were
chemically functionalized by transesterification with canola oil fatty acid
methyl ester (CME). CME performs as both the reaction reagent and solvent.
Transesterified CNC (CNCFE) was characterized for their chemical structure,
morphology, crystalline structure, thermal stability, and hydrophobicity.
Analysis by Fourier transform infrared (FTIR) and FT-Raman spectroscopies showed
that the long chain hydrocarbon structure was successfully grafted onto CNC
surfaces. After transesterification the crystal size and crystallinity of
nanocrystals were not changed as determined by Raman spectroscopy and wide angle
X-ray diffraction (XRD). CNCFE showed higher thermal stability and smaller
particle size than unmodified CNCs. Water contact angle measurement indicated the
CNCFE surface has significantly higher hydrophobicity than unmodified CNCs. The
transesterified CNCs could be potentially used as hydrophobic coatings and
reinforcing agents to hydrophobic polymer for nanocomposites.
PMID- 28504127
TI - Complexation of kappa-carrageenan with gelatin in the aqueous phase analysed by
1H NMR kinetics and relaxation.
AB - The 1H NMR spectroscopy is used to study the kinetics of gelation in the aqueous
mixtures of kappa-carrageenan with gelatin. The time dependence of NMR signals
intensities shows that the kinetics of gel formation consists of classical 'fast'
(rate constant k~6h-1) and 'slow' (k~1h-1) periods, corresponding to a coil
>helix transition and subsequent aggregation of helices. Upon increase of the
kappa-carrageenan/gelatin (w/w) ratio Z the rate of the fast process slows down
by a factor of 1.6-2.4. Further analysis was done by studying the dependence of
spin-spin relaxation times of protons of gelatin on Z in the aqueous phase. A
qualitative scheme describing hydrogel formation in the complex solution is
given. It is hypothesized that at higher concentration of PECs the hydrogel
structure network is stabilized by three types of nodes: triple helices of
gelatin and intra-/inter-molecular double helices of kappa-carrageenan.
PMID- 28504128
TI - Combined emulsifying capacity of polysaccharide particles of different size and
shape.
AB - The aim of this study is to understand mixed systems of two types of particles
with different size and shape, quinoa starch granules (NQ) and cellulose
nanocrystals (CNC), to stabilize oil-in-water (O/W) emulsions. This study
considers the extent of Pickering stabilization with respect to which particle
type dominates at droplet interfaces and how stability is affected by the
addition of one particle type to already formed emulsions, or combining both,
simultaneously. Results demonstrate that the order of addition has an influence
allowing to predominantly have NQ particles at the interface when both types are
added simultaneously. However when CNC is added first, both types are responsible
for emulsion stabilization leading to a system with an intermediate droplet size
yet with a higher stability compared to single particle formulations. A dual
stabilization mechanism is observed, large particles prevent coalescence and
small particles regulate the curvature of the interface and govern the droplet
size.
PMID- 28504129
TI - Tunicate cellulose nanocrystals reinforced nanocomposite hydrogels comprised by
hybrid cross-linked networks.
AB - Cellulose nanocrystals are considered as promising biomass nanofillers for
polymeric hydrogels, but poor interface compatibility between cellulose
nanocrystals and hydrogel matrix usually reduces their reinforcement effect.
Here, we reported a novel interface compatible nanocomposite hydrogel prepared by
introducing quaternized tunicate cellulose nanocrystals (Q-TCNCs) into chemically
cross-linked poly (acrylic acid) (PAA) networks. Q-TCNCs acted as both
nanofillers and physical cross-linkers in the PAA networks, and the electrostatic
interaction between the positive charges of Q-TCNCs and negative charges of PAA
chains improved their interface compatibility. The nanocomposite hydrogels
exhibited controllable swelling ratio and pH-sensitive swelling behaviors. The
mechanical properties of hydrogels significantly increased after incorporation of
Q-TCNCs. Moreover, the nanocomposite hydrogels exhibited partly recoverable
ability due to the presence of reversible electrovalent bonds in the hydrogel
networks.
PMID- 28504130
TI - Bifidobacterial growth stimulation by oligosaccharides generated from olive tree
pruning biomass.
AB - This work aims to evaluate the prebiotic potential of oligosaccharides (OS)
obtained from autohydrolysis of olive tree pruning biomass (OTPB). Two selected
fractions (F1 and F2) were characterized and used in in vitro fermentations by
two Bifidobacterium spp. (B. adolescentis and B. longum) and one fecal inoculum.
The fraction F1 presented a lower average degree of polymerization (DP) mainly
with OS ranging from 3 to 6 DP, whereas the fraction F2 corresponded to a pool of
unsubstituted and acetylated oligomers with DP between 4 and 19. In the
fermentation by Bifidobacterium, F1 supported a higher biomass formation, OS
consumption and organic acids production than F2. With the fecal inoculum, the
accumulation of organic acids, as the sum of acetate, propionate and butyrate,
was similar for F1 and F2 (107 and 101mM, respectively). The bifidobacteria
counts also increased during the incubation time for both OS fractions.
PMID- 28504131
TI - Electrospun core-shell structured nanofilm as a novel colon-specific delivery
system for protein.
AB - A novel core-shell structured nanofilm for the delivery of protein to the colon
was developed by coaxial electrospinning using bovine serum albumin (BSA) as
protein model. Firstly, the BSA-loaded chitosan nanoparticle was prepared by
ionic gelation, and then the coaxial nanofilm was fabricated using alginate as
shell layer and the BSA-loaded chitosan nanoparticle as core layer. Scanning
electron microscopy analysis showed that the obtained nanofilm exhibited a smooth
surface, and the core-shell structure was evidenced by the aid of transmission
electron microscopy. There was little change in the secondary structure of
encapsulated BSA and around 75% of BSA was released in the simulated colonic
fluid. The corresponding kinetics models of BSA release in different simulated
digestive fluids were built and the results revealed that the release of BSA in
colon followed a complex mechanism. This study shows that electrospun nanofilm is
a promising colon-specific delivery system for bioactive protein.
PMID- 28504132
TI - Non-destructive and direct determination of the degree of substitution of
carboxymethyl cellulose by HR-MAS 13C NMR spectroscopy.
AB - We report on the direct assessment of the degree of substitution (DS) of
carboxymethyl cellulose (CMC) by High Resolution Magic Angle Spinning (HR-MAS)
13C NMR spectroscopy. The method is applied to industrial CMCs with low and high
viscosity and nominal DS, purified and technical samples, and from cellulose
linters or wood. The preparation of a set of purified CMC working standards with
accurate DS values for the method validation is also described. The DS values
determined via HR-MAS 13C NMR on the industrial samples are critically compared
to the corresponding values achieved through the USP 37 <281> method (ASH method)
and the HPLC method, and the advantages and limitations of the HR-MAS NMR method
highlighted. Finally, the HR-MAS NMR approach allowed the accurate DS assessment
in CMC with low DS, characterized by a non-negligible fraction of non
functionalized cellulose. The proposed "effective DS" accounts for the DS of the
solvent-exposed CMC.
PMID- 28504133
TI - Nanofibrillation of deep eutectic solvent-treated paper and board cellulose
pulps.
AB - In this work, several cellulose board grades, including waste board, fluting, and
waste milk container board, were pretreated with green choline chloride-urea deep
eutectic solvent (DES) and nanofibrillated using a Masuko grinder. DES-treated
bleached chemical birch pulp, NaOH-swollen waste board, and bleached chemical
birch pulp were used as reference materials. The properties of the nanofibrils
after disc grinding were compared with those obtained through microfluidization.
Overall, the choline chloride-urea DES pretreatment significantly enhanced the
nanofibrillation of the board pulps in both nanofibrillation methods-as compared
with NaOH-treated pulps-and resulted in fine and long individual nanofibrils and
some larger nanofibril bunches, as determined by field emission scanning electron
microscopy and transmission electron microscopy. The nanofibril suspensions
obtained from the DES pretreatment had a viscous, gel-like appearance with shear
thinning behavior. The nanofibrils maintained their initial crystalline structure
with a crystallinity index of 61%-47%. Improved board handsheet properties also
showed that DES-treated and Masuko-ground waste board and paper nanocellulose can
potentially enhance the strength of the board. Consequently, the DES chemical
pretreatment appears to be a promising route to obtain cellulose nanofibrils from
waste board and paper.
PMID- 28504134
TI - Morphology, transport characteristics and viscoelastic polymer chain confinement
in nanocomposites based on thermoplastic potato starch and cellulose nanofibers
from pineapple leaf.
AB - Eco-friendly "green" nano composites were fabricated from potato starch and
cellulose nanofibers from pineapple leaf. Nanocomposites of starch/cellulose
nanofibers were prepared by solution mixing followed by casting. The
investigation of the viscoelastic properties confirms starch macromolecular chain
confinement around the nano scale cellulose surface, superior dispersion and very
good interaction between thermoplastic starch and cellulose nanofibers. The
degree of chain confinement was quantified. The chain confinement was associated
with the immobilization of the starch macromolecular chains in the network formed
by the nano-scale cellulose fibers as a result of hydrogen boding interactions.
From the results, it was assumed that the starch glycerol system exhibits a
heterogenous nature and cellulose nanofibers tend to move towards glycerol rich
starch phase. Barrier properties also improved with the addition of nanofiller up
to 3wt.% but further addition depreciated properties due to possible fiber
agglomeration. The kinetics of diffusion was investigated and typical kinetic
parameters were determined and found that the nanocomposites follow pseudo
fickian behaviour. The outcome of the work confirms that the prepared
nanocomposites films can be used as a swap for packaging applications.
PMID- 28504135
TI - A versatile method for the surface tailoring of cellulose nanocrystal building
blocks by acylation with functional vinyl esters.
AB - Herein we propose a versatile method for the surface tailoring of cellulose
nanocrystals (CNCs) based on the reactivity of vinyl ester molecules toward the
accessible hydroxyl groups located at the surface of the nanoparticles. CNCs
produced from wood pulp were acylated in various conditions, with potassium
carbonate as catalyst and under microwave activation. The impact of solvent,
temperature and reagent concentration on the reaction efficiency and kinetics was
then investigated, using vinyl acetate as a model vinyl ester. Results indicated
that the chemical reactivity was significantly influenced by the quality of the
CNCs dispersion in the solvent of reaction, the ratio of reagent relative to the
CNCs surface OH groups, the diffusion of reagent and catalyst within the CNCs
aggregates, and the different nucleophilic strengths of the surface hydroxyl
groups. The versatility of the method was verified by extending the reaction to a
selection of vinyl esters bearing various functionalities.
PMID- 28504136
TI - Fabrication of Sustained-release CA-PU Coaxial Electrospun Fiber Membranes for
Plant Grafting Application.
AB - Plant grafting is a well-known activity in orchards, greenhouses and vineyards
gardens. However, low survival rate still limits the promotion of grafting and
breeding of improved varieties. We report on polymeric fibers, obtained through
coaxial electrospun, as carriers for the sustained release of drugs to heal
wounds in plants. The CA-PU co-electrospun fibers show a rather uniform diameter,
a smooth and hydrophilic surface. As long as 10days of sustained drugs release
meets with the physiological requirement of plant grafting. The callus toxicity
test shows that the CA-PU fibers are not toxic for plant cells. We show that
loading the core of CA-PU fibers with 6-Benzylaminopurine (6-BA), a first
generation synthetic cytokinin that elicits plant growth and development, results
in fibers that can efficiently promote the healing of plant wounds, thereby
significantly improving the grafting survival rate.
PMID- 28504137
TI - Gelation of Na-alginate aqueous solution: A study of sodium ion dynamics via NMR
relaxometry.
AB - Sodium alginate (SA) hydrogels have a wide range of applications including tissue
engineering, drug delivery and formulations for preventing gastric reflux. The
dynamics of sodium ions during the gelation process of SA solution is critical
for clarification of the gelation procedure. In this work, nuclear magnetic
resonance (NMR) relaxometry and pulsed-field-gradient (PFG) NMR diffusometry were
used to investigate the dynamics of the sodium ions during the gelation of SA
alginate. We find that sodium ions are in two different states with the addition
of divalent calcium ions, corresponding to Ca2+ crosslinked and un-crosslinked
regions in the hydrogels. The sodium ions within the un-crosslinked regions are
those released from the alginate chains without Ca2+ crosslinking. The relative
content of sodium ions within the Ca2+ crosslinked regions decreased with the
increase in the content of calcium ions in the system. The relaxation time T2 of
sodium ions within the Ca2+ crosslinked and un-crosslinked regions shift to
shorter and longer relaxation time with the increase in concentration of calcium
ion, which indicates the closer package of SA chains and the larger space for the
diffusion of free sodium ions. This work clarifies the dynamics of 23Na+ in a
calcium alginate gel at the equilibrium state.
PMID- 28504138
TI - Hybrid pectin-based biosorbents for zinc ions removal.
AB - In this paper, a set of the hybrid biosorbents, made of pectin and polysaccharide
additives (arabic, tragacanth, guar, karaya, xanthan, gellan, carob gums, agar
agar) or lecithin (phospholipid), was investigated and tested for zinc ions
removal. The immobilization of the polysaccharides into the pectin matrix was
proved by the IR spectroscopy. The structure of the working biosorbents was
observed in SEM micrographs. The influence of the additive type and pH on the
sorption properties and swelling index was investigated. The maximum sorption
capacities were achieved in pH above 4 and ranged from 17.7 to 25.4mg/g for
lecithin and xanthan gum as additives, respectively. The results show that the
hybrid pectin-based beads are promising biosorbents for zinc removal from aqueous
solutions.
PMID- 28504139
TI - The protective role of phytate in the oxidative degradation of cereal beta
glucans.
AB - This study investigated the role of phytate in the Fenton reaction induced
oxidative degradation of cereal beta-glucan. Viscosity analysis showed that the
degradation rate was high in the beginning of oxidation, which fitted to the
second order kinetic model. Oat beta-glucan contained significant amount of
residual phytate and after the residual phytate was removed, faster degradation
was shown compared to the original oat beta-glucan. Adding the same amount of
phytic acid (PA) to the phytate removed beta-glucan sample also retarded the
degradation but not as efficiently as the residual phytate. Considerable
retardation of viscosity loss was shown when the PA to iron ratio was high. The
presence of ascorbic acid weakened the retardation effect of phytic acid. Thus,
phytate can significantly improve the oxidative stability of beta-glucan when the
ratio of phytic acid to transition metals and the presence of ascorbic acid are
taken into consideration.
PMID- 28504140
TI - DFT study on the dissolution mechanisms of alpha-cyclodextrin and chitobiose in
ionic liquid.
AB - Density functional theory (DFT) was employed to study the dissolution mechanisms
of alpha-cyclodextrin and chitobiose in 1-ethyl-3-methyl-imidazolium acetate
([Emim][OAc]). Geometrical analysis of the studied complexes indicated that both
anion and cation in ionic liquid interacting withalpha-cyclodextrin and
chitobiose contributed to the dissolution reaction. Intermolecular interactions
in the complexes were identified as non-covalent interactions, such as hydrogen
bonds, van der Waals interactions and repulsions, which were considered as the
driving force of dissolution. Among them, hydrogen bonding interactions played a
dominant role, which was further visualized in the real space by combination of
atoms in molecules (AIM) and reduced density gradient (RDG) techniques. The
nature of intermolecular orbital interactions was characterized using natural
bond orbital (NBO) theory.
PMID- 28504141
TI - Starch/MWCNT-vitamin C nanocomposites: Electrical, thermal properties and their
utilization for removal of methyl orange.
AB - In the present study, the surface of multiwalled carbon nanotubes (MWCNT)s is
modified by ascorbic acid (AA) (vitaminC) for their dispersion improvement in the
starch matrix. Then, the starch-based nanocomposites (NCs) containing 3, 6 and
9wt% of AS modified MWCNTs (AA-MWCNT)s were fabricated via ultrasonication
method. Characterization of the prepared NCs was accomplished by different
techniques. The optimum MWCNT content for the generation of fine electrical
conductivity was found to be about 3wt%, indicating better dispersion of AA-MWCNT
with low amount of AA-MWCNT. The adsorption efficiency of starch/AA-MWCNTs NCs is
examined using methyl orange (MO) as adsorbate. Finally, it is concluded that
starch/AA-MWCNTs NC is an effective adsorbent for the uptake of MO dye from
aqueous solution.
PMID- 28504142
TI - Prebiotic efficacy and mechanism of inulin combined with inulin-degrading
Lactobacillus paracasei I321 in competition with Salmonella.
AB - Inulin efficacy was proven for raising anti-Salmonella activity of the inulin
degrading Lactobacillus paracasei I321 (infant isolate) through the mechanisms of
antibacterial secretion and competitive adhesion. Inulin significantly promoted
competitive adhesion of L. paracasei I321 against many Gram-negative foodborne
pathogenic bacteria. Salmonella Typhimurium SA2093 was completely suppressed
under highly competitive niche of fecal microflora when inulin, L. paracasei
I321, and their synbiotic combination were applied. Inulin supplementation
obviously alleviated nutrient limitation in the mimicked proximal colon leading
to complete destruction of Salmonella. This was achieved through the manipulation
of fecal bifidobacteria which subsequently altered antibacterial metabolites.
Acetate was the major metabolite correlating to high number of fecal
bifidobacteria in the presence of inulin, whereas lactate became dominant when L.
paracasei I321 was coupled. This inulin-degrading strain was able to persist and
dominate in the competitive environment of fecal microflora and functioned
synergistically with inulin to completely destroy Salmonella.
PMID- 28504143
TI - Thermal and mechanical properties of tailor-made unbranched alpha-1,3-glucan
esters with various carboxylic acid chain length.
AB - The convenient and environmentally friendly method for in vitro polymerization
catalyzed by glucosyltransferase, designated as GtfJ, extracted from recombinant
E. Coli was used to synthesize tailor-made alpha-1,3-glucan (alpha-1,3-d-glucan)
having moderate molecular weight (Mw=2.0*105) and no branches. With the aim to
improve thermoplasticity of this polysaccharide, after in vitro synthesis,
chemical modification by acylation was selected and then fully substituted alpha
1,3-glucan esters were successfully obtained via both homogeneous and
heterogeneous methods. Thermal degradation temperature of alpha-1,3-glucan esters
was improved after esterification and dependent on neither side chain length nor
synthesis methods. DSC curves suggested a presence of crystal structure in alpha
1,3-glucan acetate, propionate, butyrate, valerate and hexanoate due to
detectable melting endotherm, whereas octanoate exhibited amorphous behavior.
Tm's of alpha-1,3-glucan esters were relatively high, more than 200 degrees C, in
comparison with commercial plastics. The shorter chain length of acid component,
the higher Tm and Tg ester products exhibited. In addition, tensile strength of
alpha-1,3-glucan esters decreased in contrast with elongation at break with an
increase in alkyl chain length of an acid component. Thus, crystalline and
amorphous alpha-1,3-glucan esters with adjustable thermal and mechanical
properties obtained from this research are promising materials for continuing
applied researches and contemplating the future application in bio-based
thermoplastic materials.
PMID- 28504144
TI - Low molecular weight xanthan gum suppresses oxidative stress-induced apoptosis in
rabbit chondrocytes.
AB - We have previously reported the application of low molecular weight XG(LM-XG),
with molecular weights ranging from 1*106Da to 1.5*106Da for treating
osteoarthritis. In this study, we investigated the anti-apoptotic activity of LM
XG under oxidative stress conditions, activated by hydrogen peroxide (H2O2)
treated chondrocytes in vitro. Chondrocytes were pretreated with various doses of
LM-XG (0, 10, 100, 500, or 1000MUg/mL) or 1000MUg/mL sodium hyaluronate for 12h,
and then exposed to 0.5mmol/L H2O2 for another 12h. After treatment, chondrocyte
viability was evaluated using a cell counting kit-8; DNA fragmentation was
detected using Hoechst33258 staining; the percentage of DNA fragmentation was
evaluated using the diphenylamine DNA assay kit; the apoptosis rate was evaluated
using flow cytometry; chondrocyte ultra-microscopic morphology was observed using
transmission electron microscopy; intracellular reactive oxygen species levels
were observed and quantified using 2,7-dichlorofuorescin diacetate, mitochondrial
permeability transition analysis was performed using MitoTracker Red CMXRos and
4',6-diamidino-2-phenylindole staining; and finally, caspase-3 activity was
detected by western blot. The results showed that, compared with H2O2-treated
chondrocytes, LM-XG improved cell viability, decreased the percentage of DNA
fragmentation, reduced the apoptosis rate, decreased the levels of intracellular
reactive oxygen species and mitochondrial permeability transition, reverted the
morphological damage, and downregulated cleaved caspase-3 levels. These results
demonstrate that LM-XG has anti-apoptotic activity in H2O2-treated chondrocytes.
PMID- 28504145
TI - Preparation and properties of carbohydrate-based composite films incorporated
with CuO nanoparticles.
AB - The present study aimed to develop the carbohydrate biopolymer based
antimicrobial films for food packaging application. The nanocomposite films of
various biopolymers and copper oxide nanoparticles (CuONPs) were prepared by
solvent casting method. The nanocomposite films were characterized using SEM,
FTIR, XRD, and UV-vis spectroscopy. The thermal stability, UV barrier, water
vapor permeability, and antibacterial activity of the composite films were also
evaluated. The surface morphology of the films was dependent on the types of
polymers used. The XRD revealed the crystallinity of CuONPs in the composite
films. The addition of CuONPs increased the thickness, tensile strength, UV
barrier property, relative humidity, and water vapor barrier property. The CuONPs
incorporated composite films exhibited strong antibacterial activity against
Escherichia coli and Listeria monocytogenes. The developed composite films could
be used as a UV-light barrier antibacterial films for active food packaging.
PMID- 28504146
TI - Lignin-coated cellulose nanocrystal filled methacrylate composites prepared via
3D stereolithography printing: Mechanical reinforcement and thermal
stabilization.
AB - Various contents of lignin-coated cellulose nanocrystals (L-CNC) were
incorporated into methacrylate (MA) resin and their mixture was used to prepare
nanocomposites via 3D stereolithography (3D-SL) printing. Gaps were found between
the L-CNC and MA matrix in 3D-SL printed nanocomposites before postcure. However,
gaps decreased after postcure due to interactions between the L-CNC and MA
molecules. Mechanical properties increased with the addition of 0.1% and 0.5% L
CNC after postcure, and the thermal stability was improved at 0.5% L-CNC. Dynamic
mechanical analysis demonstrated that incorporation of L-CNC increased the
storage modulus in the rubbery plateau. The loss factor had two transition
regions, which gradually changed by merging together with increasing L-CNC
content, and a broadening of the transition region was observed after postcure.
In particular, the mechanical and thermal properties of 3D-SL printed
nanocomposites, after postcure, exhibited higher improvement than those before
postcure.
PMID- 28504147
TI - Synthesis and characterization of cellulose-goethite composites and their
adsorption properties with roxarsone.
AB - This study reports on the preparation of goethite and its supported forms onto
cellulose as adsorbents for the adsorption of 4-hydroxy-3-nitrobenzene arsenic
acid (roxarsone) from aqueous solution. Goethite nanoparticles (NPs) and their
cellulose composites were prepared with good yield ~97%, and characterized by
thermal gravimetric analysis (TGA), Fourier transform infrared (FTIR)
spectroscopy, Raman spectroscopy, nitrogen gas adsorption/desorption (BET),
powder X-ray diffraction (pXRD) and transmission electron microscopy (TEM). The
monolayer uptake (Qm) capacity of goethite was 19.2mg/g while the Qm value for
30% Fe coated goethite-cellulose (GC) was 17.4mg/g. The greater content and
dispersion of goethite NPs contribute active sites on the cellulose surface to
yield greater uptake of roxarsone for the Fe loaded GC composites. GC composites
are a cost effective and efficient way to disperse goethite NPs onto cellulose
surface for the enhanced adsorption of roxarsone. The GC composites reduce NP
leaching whilst maintaining comparable uptake of arsenic species at 30% iron
oxide doping that rival the adsorption properties of the pure mineral phase of
goethite.
PMID- 28504148
TI - Enhanced emulsifying properties of wood-based cellulose nanocrystals as Pickering
emulsion stabilizer.
AB - Cellulose nanocrystals are hydrophilic nanomaterials, which limits their
applications as interfacial compounds. Herein, we propose using modified wood
based cellulose nanocrystals as Pickering emulsion stabilizer. Wood cellulose was
consecutively oxidized and modified with phenyltrimethylammonium chloride to
create hydrophobic domains comprised of phenyl groups. These modified oxidized
cellulose nanocrystals (m-O-CNCs) were homogeneous/electrostatically stable in
water and they can stabilize O/W Pickering emulsions. The dispersed phase volume
fraction (DPVF) of the Pickering emulsion was 0.7 at around 1.5g/L, whereas the
tween-20 control needed a 13-fold greater concentration to have a similar DPVR.
In addition, these m-O-CNC stabilized Pickering emulsions also showed good
mechanical and thermal stability against centrifugation and heat, as well as size
controllability. In terms of stability, size controllability, surfactant-free
status, these m-O-CNCs possess superior and enhanced emulsifying properties.
Future research for these new interfacial materials have potential in
applications, for personal care, cosmetic and pharmaceutic industries.
PMID- 28504149
TI - Post-screening characterisation and in vivo evaluation of an anti-inflammatory
polysaccharide fraction from Eucommia ulmoides.
AB - We report here the discovery of a polysaccharide, namely EUP1, with anti
inflammatory activity from the herb of Eucommia ulmoides Oliv. We separated three
polysaccharide fractions from this herb based on acidity and screened them for
their activity in modulating the phenotype of murine macrophages. Among them,
EUP1 was the only fraction to exert such a function - it stimulated Raw 264.7
cells to express CD206 and a key anti-inflammatory cytokine interleukin-10.
Having fully characterised EUP1 with a series of chromatographic and
spectroscopic analyses, we evaluated its anti-inflammatory effects in both in
vitro and in vivo inflammatory models. In the murine model of sepsis induced by
lipopolysaccharide, administration of EUP1 effectively suppressed the expression
of major inflammatory cytokines, alleviated lung injury and increased animal
survival rate. In summary, EUP1, with a clearly elucidated chemical structure and
solid anti-inflammatory activity, may become a valuable candidate for further
development into an anti-septic therapeutic agent.
PMID- 28504150
TI - Characteristics of unique HBr-hydrolyzed cellulose nanocrystals from freshwater
green algae (Cladophora rupestris) and its reinforcement in starch-based film.
AB - Cellulose nanocrystals (CNCs) are promising materials that are readily extracted
from plants and other cellulose-containing organisms. In this study, CNCs were
isolated from freshwater green algae (Cladophora rupestris) thriving in a
volcanic lake, using hydrobromic acid (HBr) hydrolysis. Morphological and
structural studies revealed highly crystalline CNCs (94.0% crystallinity index)
with preferred orientation to [100] lattice plane as shown by XRD measurements
and have an average diameter of 20.0 (+/-4.4)nm as shown by TEM. Thermal studies
showed increased temperature for thermal decomposition of CNCs (381.6 degrees C),
which is a result of HBr hydrolysis for CNCs isolation. The isolated CNCs were
reinforced into starch based biocomposites via solution casting and evaporation
method. Mechanical strength was improved as high as 78% upon addition of 1%
cellulose nanocrystals in the films. The produced films are promising materials
for their high mechanical strength, biodegradability and availability of raw
materials.
PMID- 28504151
TI - The fabrication of microcrystalline cellulose-nanoZnO hybrid composites and their
application in rubber compounds.
AB - Microcrystalline cellulose (MCC) was first swollen and then hybridized with nano
ZnO to prepare MCC-ZnO hybrid composites using a microreactor technique. The
microstructure of the ZnO particles was controlled and characterized. The results
showed that the nano-ZnO particles had a Wurtzite structure and were successfully
loaded on the surface of the MCC, and the ZnO morphologies could be shaped as
spheres, rods or tubes by controlling the size of microreactor. The hybrid ratio
of ZnO was approximately 20%. The MCC-ZnO hybrids were used in SSBR2557A/SiO2
compounds to replace portions of the silica. The results showed that MCC-ZnO
compounds had improved processing and mechanical properties compared to the pure
MCC sample. The dynamic mechanical analysis (DMA) indicated that MCC-ZnO
compounds had higher wet-skid resistance and lower rolling resistance than the
control samples. The interfacial bonding between the hybrids and rubber was also
improved; the sizes of the hybrid composites decreased in situ during the rubber
processing.
PMID- 28504152
TI - Impact of diverse cultivars on molecular and crystalline structures of rice
starch for food processing.
AB - The objective of this study was to determine the molecular and crystalline
structures of starches from diverse rice cultivars for three major food
processing in Korea (cooked rice, brewing and rice cake). Rice starches were
isolated from 10 different rice varieties grown in Korea. Apparent amylose
contents of rice starches from cooked rice, brewing and rice cake varieties were
21.1-22.4%, 22.9-24.6%, and 20.1-22.0%, respectively. Rice starches from rice
cake varieties showed higher peak viscosity but lower pasting temperature than
those from cooked rice and brewing varieties. Swelling factor at 80 degrees C of
rice starches from cooked rice, brewing and rice cake varieties was 16.6-19.0,
17.8-19.3, and 17.8-19.2, respectively. Based on structure and physicochemical
properties of rice starches extracted from different rice varieties, principal
component analysis (PCA) results showed that these rice varieties could be
clearly classified according to processing adaptability for cooked rice and rice
cake.
PMID- 28504154
TI - Simply constructed chitosan nanocarriers with precise spatiotemporal control for
efficient intracellular drug delivery.
AB - A novel intelligent nanocarrier with pH and redox sensitivities was developed
based on Carboxymethyl-chitosan (CMCS) and thioglycolic acid conjugated chitosan
(TCS) to provide precise spatiotemporal control for efficient intracellular
delivery. Doxorubicin (DOX) loaded nanocarriers (DOX/CMCS-TCS NPs) were simply
prepared by ionic gelation and then oxidation crosslink. The nanocarriers
exhibited decent stability at pH 7.4 for up to 3days and underwent aggregation
under acidic pH (5.5) due to protonation of the carboxyl groups on CMCS. The TCS
skeleton was stable at pH 5.5 (mimic endo/lysosomes) but disintegrated in the
presence of 10mM glutathione (GSH) at pH 7.4 (mimic cytosol). In vitro DOX
release from DOX/CMCS-TCS NPs was enhanced at pH 5.5 compared with physiological
condition, with 64.2% and 31.6% DOX released in 2h, respectively. While 85.2% of
DOX was released within 2h as treated with 10mM GSH, suggesting the release was
closely associated with structural disintegration of nanocarriers. The maximum
release of DOX was obtained at 10mM GSH and pH 5.5 with 92.3% of DOX released in
5h. Confocal laser scanning microscopy observation indicated that DOX/CMCS-TCS
NPs efficiently escaped from endo/lysosomes within 1h incubation with MCF-7 cells
and gave the best performance in delivering DOX into nucleus in 2h. Anticancer
activity assay revealed that DOX/CMCS-TCS NPs had comparable or even better
inhibition of cell viability at high drug concentrations than free DOX, with the
IC50 of 0.6MUg/mL following 48h incubation. In summary, the simply constructed
DOX/CMCS-TCS NPs could not only respond to intracellular delivery temporally,
they also achieve rapid release spatially in nucleus, which provide a precise
spatiotemporal control of drug delivery for cancer therapy.
PMID- 28504153
TI - Injectable hyaluronic acid/poly(ethylene glycol) hydrogels crosslinked via strain
promoted azide-alkyne cycloaddition click reaction.
AB - This paper reports injectable hyaluronic acid (HA)-based hydrogels crosslinked
with azide-modified poly(ethylene glycol) (PEG) via the strain-promoted azide
alkyne cycloaddition (SPAAC) between cyclooctyne and azide groups. Cyclooctyne
modified HA (Cyclooctyne-HA) is prepared by the reaction of HA with 2
(aminoethoxy)cyclooctyne. To crosslink the modified HA, quadruply azide
terminated poly(ethylene glycol) (Azide-PEG) is designed and prepared. The
mixture of Cyclooctyne-HA and Azide-PEG gelates in a few minutes to form a strong
HA-PEG hydrogel. The hydrogel has fast gelation time, good strength, and slow
degradation rate, because of the high reactivity of SPAAC, high crosslinking
density originated from the quadruply-substituted Azide-PEG, and the good
stability of the crosslinking amide bonds. In vitro cell culturing within the
hydrogel demonstrated an excellent cell-compatibility. The bioorthogonality of
SPAAC makes the hydrogel injectable. With good mechanical properties and
biocompatibility, the hydrogel would be useful in a wide range of applications
such as injection filling materials for plastic surgery.
PMID- 28504155
TI - Structural and physicochemical properties of granular starches after treatment
with debranching enzyme.
AB - The present study modified maize and potato granular starches by partial
debranching treatment below the gelatinization temperature, and investigated
their structural and physicochemical properties. Pullulanase was much effective
(more than three times) on hydrolyzing potato starch compared to maize starch as
measured from total carbohydrate values in the supernatant. The pullulanase
hydrolysis decreased the amount of double helices as observed from DSC
measurement. These effects were dependent upon the time of enzyme hydrolysis
(24h>8h>1h) as well as type of starch (potato>maize). The pullulanase hydrolysis
decreased the peak viscosity of the potato starch paste, whereas the effect was
very less pronounced for maize starch. The current results showed that it is
possible to achieve the starches with desired physicochemical properties by
varying the starch type as well as modification process.
PMID- 28504156
TI - Poly(N-methacryloyl glycine)/nanocellulose composites as pH-sensitive systems for
controlled release of diclofenac.
AB - The present study reports the development of non-cytotoxic and pH-sensitive
nanostructured membranes consisting of a polymer with amino acid pending moieties
and bacterial nanocellulose (BC). The nanocomposites were prepared through a
simple methodology under green reaction conditions. The obtained materials
display good thermal stability (up to 200 degrees C), viscoelastic (storage
modulus>700MPa) and mechanical (Young's modulus=3.5-4.9GPa) properties, together
with high water uptake capacity. The results of the in vitro MTT assay showed
that the nanocomposites are non-cytotoxic to HaCaT cells for 72h. The in vitro
release profile of diclofenac sodium salt (DCF) from the nanocomposites into
simulated body fluids at different pH values demonstrates the pH-responsive
behaviour of these materials. Besides, DCF is mainly retained in the
nanocomposites at pH 2.1 and released at pH 7.4, revealing their potential for
the controlled release of DCF in dermal as well as in oral drug delivery
applications.
PMID- 28504157
TI - Biomacromolecular-based ionic-covalent hydrogels for cell encapsulation: The
atelocollagen - Oxidized polysaccharides couples.
AB - Mixed crosslinked networks of ionic-covalent entanglement type were prepared
starting from ternary mixtures of atelocollagen (aK; as fibrillary matrix
generator), sodium hyaluronate (NaHyal; a microfibrillation assistant), and
oxidized polysaccharides (OxPolys; as both cross-linkers and matrix fillers), and
were tested as hydrogels for eukaryotic cell encapsulation. Either oxidized
gellan (GellOx) or pullulan (PullOx) were used. An original procedure and optimal
hydrogel recipes were developed to encapsulate fibroblasts and adipose-derived
stem cells, while preserving their viability and proliferative ability during ex
vivo temporarily storage. Physical-chemical, rheological, and biocompatibility
properties of the prepared hydrogels were compared against the classic alginate
hydrogel used for cell encapsulation. A larger range of material characteristics
(from lax to stiff) and better laboratory maneuverability were demonstrated,
which permit to design appropriate compositions for particular cell types. All
hydrogels undergo fast liquefaction at temperatures between 42 and 50 degrees C,
permitting the cell release after a short innocuous thermal shock.
PMID- 28504158
TI - Influence of osmotic and weight pressure on water release from polysaccharide
ionic gels.
AB - Kappa-carrageenan (kC) is a polyelectrolyte biopolymer that forms gels if the kC
concentration, the salt and the temperature are adequately chosen. Actually,
under certain conditions, kC gels release water in a process called syneresis. In
this contribution, the syneresis of gels containing 2g/L of kC has been studied
as a function of potassium chloride concentration [KCl]. The syneresis decreases
if the [KCl] is increased in the biopolymer solution (sol) before the gelation
but increases if the [KCl] is increased after gelation by immersing the gels in
KCl solution. The surrounding phase induces an osmotic pressure (Pi), which
increases if the [KCl] difference between the inside and outside of the gel
increases. Swelling has been observed for negative Pi. A method that enables the
exudate to be removed continuously demonstrated the effect of the strain caused
by the gel's own weight on syneresis. Increasing the KCl concentration in the sol
promotes syneresis due to strain. The analysis of the syneresis kinetics of
different systems has enabled the creation of a pressure-induced syneresis
diagram. This diagram will contribute to controlling the mouthfeel of chewing
products.
PMID- 28504159
TI - Preparation and properties of zein-rutin composite nanoparticle/corn starch
films.
AB - Edible active films were prepared based on zein-rutin composite nanoparticles
(RNs) and corn starch (CS). RNs (0, 0.5, 1, 2, 4, and 10%, w/w) were incorporated
into CS films, to act as a natural antioxidant. Scanning electron microscopy and
Fourier-transform infrared spectroscopy were used to examine the morphology and
functional group interactions. The tensile strength and elongation at break
increased from 1.19 to 2.42MPa, and from 42.10 to 78.84%, respectively, with
increasing RN loading. The incorporation of RNs led to the formation of a net
like structure, which decreased the water vapor permeability and water solubility
of the RN-CS film. The cumulative amount of rutin detected in vitro after 12h was
27.1-36.9% of the total amount of rutin. The RNs dispersed in the CS film
provided controlled release of rutin. The antioxidant capacities of the films
were greater than that of the pure CS film.
PMID- 28504160
TI - Effect of molecular weight on the ability of guar gum to enhance "weak gel"
rheology of microdispersed oxidised cellulose (MDOC).
AB - MDOC comprises small, essentially insoluble, particles which associate to form
"weak gel" networks at concentrations above ~4wt%. Association is promoted by
guar gum, causing an increase in G' at low levels of addition and a decrease at
higher concentrations, due to excessive aggregation of the MDOC particles. For
guar gum samples with molecular weights ranging from ~60 to ~1800kDa, we found
that the concentration required to give maximum G' for 5wt% dispersions of MDOC
increased systematically from ~0.005wt% for the lowest molecular weight to
~0.3wt% for the highest. We propose that guar gum drives self-association of MDOC
to reduce enthalpically-unfavourable (segregative) interactions between the two
materials, and that large coils are less effective than smaller ones because a
higher proportion of chain sequences are buried in the interior of the coil,
where they cannot make segmental contacts with the MDOC particles.
PMID- 28504161
TI - Rapid fabrication of TiO2@carboxymethyl cellulose coatings capable of shielding
UV, antifog and delaying support aging.
AB - Agricultural plastic films capable of shielding UV, filtering visible light and
antifog are important to prolong their life and protect safeties of
agriculturists and crops. In this work, high stable and small size TiO2@polymer
nanoparticles (NPs) were prepared by an efficient one-pot microwave synthesis
using titanic sulfate as Ti resource, carboxymethyl cellulose sodium (CMC) as
complexing agent and stabilizer. The TiO2@CMC NPs obtained were then utilized to
fabricate poly(ethylene imine) (PEI)/TiO2@CMC coatings on the surface of
polypropylene films by a layer-by-layer assembly technique. The TiO2@CMC NPs show
rapid deposition rate because small, spherical and anion-rich TiO2@CMC NPs
possess large specific surface area and fast diffusion rate. More importantly,
property experiments confirm that (PEI/TiO2@CMC)*15 coatings can not only
effectively shield UV rays, filter visible light and prevent fogging but also
delay the aging of their supports.
PMID- 28504162
TI - Purification of glucomannan from salep: Part 2. Structural characterization.
AB - The aim of this study was to investigate the effects of different extraction
temperatures (25, 55 and 85 degrees C) on the structural characteristics of
glucomannan (GM) purified from salep. All extraction conditions reduced protein
content and molecular weight of salep. The effectiveness of removing the
impurities and the highest purity of GM25 were observed with size exclusion
profile. FTIR experiments demonstrated the presence of acetyl group, reduction of
protein content and increment of polymer interaction of GM25. XRD patterns of
GM25 with narrower and higher intensity than GM55, GM85 and native salep
indicated strengthened interaction of GM25. Higher particle size was determined
for GM25. The degradation peak observed with DSC increased from 293 to 314
degrees C and GM25 had the higher thermal stability which was also supported with
TGA results. These results could provide widening the applications in food
industry and other fields and also progressing development of salep with a better
structural characteristic.
PMID- 28504163
TI - Effects of immobilization, pH and reaction time in the modulation of alpha-, beta
or gamma-cyclodextrins production by cyclodextrin glycosyltransferase: Batch and
continuous process.
AB - This study reports the immobilization of a beta-CGTase on glutaraldehyde pre
activated silica and its use to production of cyclodextrins in batch and
continuous reactions. We were able to modulate the cyclodextrin production (alpha
, beta- and gamma-CD) by immobilization and changing the reaction conditions. In
batch reactions, the immobilized enzyme reached to maximum productions of 4.9mgmL
1 of alpha-CD, 3.6mgmL-1 of beta-CD and 3.5mgmL-1 of gamma-CD at different
conditions of temperature, pH and reaction time. In continuous reactor, varying
the residence time and pH it was possible to produce at pH 4.0 and 141min of
residence time preferentially gamma-CD (0.75 and 3.36mgmL-1 of alpha- and gamma
CD, respectively), or at pH 8.0 and 4.81min alpha- and beta-CDs (3.44 and
3.51mgmL-1).
PMID- 28504164
TI - A novel water-based process produces eco-friendly bio-adhesive made from green
cross-linked soybean soluble polysaccharide and soy protein.
AB - In this study, an eco-friendly soy protein adhesive was developed that utilized
two components from soybean meal without addition of any toxic material. A plant
based, water-soluble and inexpensive soybean soluble polysaccharide was used as
the novel renewable material to combine with soy protein to produce a soy protein
adhesive. Three-plywood was fabricated with the resulting adhesive, and its wet
shear strength was measured. The results showed the wet shear strength of plywood
bonded by the adhesive reached 0.99MPa, meeting the water resistance requirement
for interior use panels. This improvement was attributed to the following
reasons: (1) Combination of cross-linked soybean soluble polysaccharide and soy
protein formed an interpenetrating network structure, improving the thermal
stability and water resistance of the cured adhesive. (2) Adding CL-SSPS
decreased the adhesive viscosity to 15.14Pas, which increased the amount of the
adhesive that penetrate the wood's surface and formed more interlocks.
PMID- 28504165
TI - Calcium silicate nanowires - An effective alternative for improving mechanical
properties of chitosan-hydroxyethyl methacrylate (HEMA) copolymer nanocomposites.
AB - Nanowires of calcium silicate were successfully synthesized by ultrasonic
irradiation process and incorporated into chitosan and hydroxyetheyl methacrylate
(HEMA) copolymer matrix by solution blending for efficacious preparation of
biodegradable nanocomposites. Remarkable improvement in mechanical properties of
the nanocomposites was noticed after micro-tensile analysis. Enlarged surface
area and higher aspect ratio of CaSiO3 nanowires were the key factors responsible
for such improvement. This was supported by EDS and XRD analysis in terms of
proper distribution of nanofiller through the copolymer matrix and corresponding
rise in percentage crystallanity respectively. Contact angle and biodegradation
studies further clarified that nano-CaSiO3 did not affect the hydrophilicity and
general degradation route of chitosan copolymer respectively. This renders the
nano-CaSiO3 as an ideal substitute for preparing high performance nanocomposites
to be applicable for biomedical applications.
PMID- 28504166
TI - Functionality of chitosan in batter formulations for coating of fish sticks:
Effect on physicochemical quality.
AB - Chitosan is a natural polymer having diverse applications in food industry. The
present study was undertaken to evaluate chitosan as a hydrocolloid in batter
composition in developing enrobed fish sticks with better functional properties
and improved quality. Different concentrations of chitosan gel were made in
acetic acid medium and incorporated into batter for making enrobed fish sticks.
Coating parameters, fat uptake, oil reduction, chemical quality parameters,
instrumental texture analysis and colour were studied. Addition of chitosan gel
had a significant effect (P<0.05) on the coating pickup, adhesion degree and
cooking yield of the product. Total volatile basic nitrogen, pH, lipid oxidation
parameters like peroxide value and thiobarbituric acid reactive substances of par
fried fish sticks also showed significant differences. The oil reduction in par
fried samples were 36.84, 65.05, 73.83, 77.65% respectively for 0.5, 1.0, 1.5,
2.0% chitosan added samples. Addition of chitosan significantly reduced
crispness, gumminess, Warner-Bratzler shear force and toughness (P<0.05) of the
product. The study clearly demonstrated that the inclusion of chitosan at 1.0% in
batter can improve functional and other quality aspects of enrobed products.
PMID- 28504167
TI - Antibacterial and antioxidative activity of O-amine functionalized chitosan.
AB - Cinnamaldehyde was immobilized to O-amine functionalized chitosan via a coupling
reaction. Fourier transform infrared spectroscopy confirmed N-cinnamyl
substitution. Wetting analyses demonstrate more hydrophobicity in the N-cinnamyl
substituted O-amine functionalized chitosan compared to chitosan or unsubstituted
O-amine functionalized chitosan. Thermal gravimetric analysis and differential
scanning calorimetry demonstrates that the prepared N-cinnamyl substituted O
amine functionalized chitosan exhibits higher thermostability than unmodified
chitosan at temperatures in which polysaccharides are commonly stored and
utilised. The N-cinnamyl substituted O-amine functionalized chitosan, against
four different bacteria strains [two gram-positive (Staphylococcus aureus and
Bacillus cereus) and two gram-negative (Escherichia coli and Pseudomonas
aeruginosa)], displays promotion of inhibition activity against these bacterial
strains. Finally, the antioxidative activity of the N-cinnamyl substituted O
amine functionalized chitosan was compared with those activities of chitosan and
O-amine functionalized chitosan. This was evaluated by uninhibited and inhibited
hyaluronan degradation and ABTS assay. The N-cinnamyl substituted O-amine
functionalized chitosan shows a lower activity towards donating a hydrogen
radical compared to chitosan or O-amine functionalized chitosan. On the other
hand, the N-cinnamyl substituted O-amine functionalized chitosan exhibited a
higher ability to scavenge the ABTS+ cation radical compared to chitosan and O
amine functionalized chitosan.
PMID- 28504168
TI - Binding efficacy and kinetics of chitosan with DNA duplex: The effects of
deacetylation degree and nucleotide sequences.
AB - The binding process of DNA duplex with various types of chitosan polymers were
studied at atomic level through molecular dynamics simulations. The interaction
kinetics and binding strength, complex morphology and DNA structure evolution
were systematically accessed. The binding efficacy of chitosan to DNA reduces
(both in complexation speed and binding strength) when deacetylation degree is
decreased, because protonated amine groups on chitosan backbone are more prone to
bind with DNA, especially the phosphate oxygen, through coulomb interaction. The
Watson Crick hydrogen bonds of A-T base pairs are more easily to break because
chitosan is capable to form competitive hydrogen bonds with them. It is
surprising to find that the G-C nucleotides have highly restrained kinetic motion
than that of A-T nucleotides, which would be important for DNA-chitosan
complexation and condensation to happen at the microscopic level. From our
current results, the degree of chitosan deacetylation is found to play a certain
role in regulating the DNA-chitosan complexation process, but is not as important
as being believed before. Other types of chemical functionalization that can tune
the chitosan's hydrophobicity should deserve more attentions in the experiment.
PMID- 28504169
TI - Acid mediated chemical treatment to remove sugar from waste acid stream from nano
crystalline cellulose manufacturing process.
AB - Nano-crystalline cellulose (NCC) is a nano-scale biomaterial derived from highly
abundant natural polymer cellulose. It is industrially produced by concentrated
acid hydrolysis of cellulosic materials. However, presences of as high as 5-10%
of sugar monomers in spent sulphuric acid during the manufacturing process, makes
it unsuitable for such recycling or reuse of sulphuric acid. Currently, the
industry has been using membrane and ion exchange technology to remove such
sugars, however, such technologies cannot achieve the target of 80-90% removal.
In the current investigation, thermal treatment and acid mediated thermal
treatment have been evaluated for sugar removal from the spent sulphuric acid.
Almost complete removal of sugar has been achieved by this approach. Maximum
sugar removal efficiency (99.9%) observed during this study was at 120+/-1
degrees C for 60min using 0.8 ratio (sample: acid) or at 100+/-1 degrees C for
40min using 1.5 ratio.
PMID- 28504170
TI - Preparation of multifunctional chitin nanowhiskers/ZnO-Ag NPs and their effect on
the properties of carboxymethyl cellulose-based nanocomposite film.
AB - Chitin nanowhiskers (ChNW) were isolated and used for the synthesis of hybrid
ChNW/ZnO-Ag NPs. The hybrid nanoparticles were used for the preparation of
multifunctional carboxymethyl cellulose (CMC) films. A ChNW was needle shape with
the width of 8-40nm, the length of 150-260nm, and crystallinity index of 93.6%.
The ZnO-Ag NPs were spherical with the diameter of 10.5-16.2nm. STEM, EDX, XRD,
and UV-vis analyses confirmed the formation of ZnO-Ag NPs on the surface of ChNW.
The thermal stability of ChNW was increased by incorporation of ZnO-Ag NPs. A CMC
based nanocomposite film incorporated with 5wt% of ChNW/ZnO-Ag NPs was
homogeneous and showed the high UV-barrier property. The tensile strength (TS)
and elastic modulus (E) of the composite film increased by 18-32% and 55-100%,
respectively, while the elongation at break (EB) decreased by 23-33%. CMC
composite films showed strong antibacterial activity against E. coli and L.
monocytogenes.
PMID- 28504171
TI - Tuneable catechin functionalisation of carbohydrate polymers.
AB - In this contribution, we present a strategy to functionalise three natural
carbohydrate polymers (dextran - a neutral polymer, sodium alginate - an anionic
polymer and chitosan - a cationic polymer) with catechin with excellent degrees
of functionality. In a first step, the carbohydrate polymers were oxidised by
sodium periodate to yield aldehyde functionalised carbohydrate polymers. The
presence of aldehyde groups was exploited to attach catechin by an acid catalysed
nucleophilic reaction. The degree of catechin functionalisation could be easily
tuned by varying the acid concentration in the reaction mixture, achieving
catechin functionalisation levels of up to 48% for dextran aldehyde catechin, 35%
for chitosan-aldehyde-catechin and 22% for sodium alginate aldehyde catechin. 1H,
1H-13C HSQC and DOSY NMR were performed to elucidate the structural differences
between the three aldehyde functionalised polysaccharides and how this affects
their reactivity and conjugation behaviour. All three carbohydrate polymer
catechin conjugates showed superior free-radical scavenging activity compared
with the non-functionalised polymers.
PMID- 28504173
TI - An all-solid-state yarn supercapacitor using cotton yarn electrodes coated with
polypyrrole nanotubes.
AB - A novel all-solid-state yarn supercapacitor (YSC) has been fabricated by using
the cotton yarns coated with polypyrrole (PPy) nanotubes. The interconnected
network structure of PPy can increase the surface area as well as the
electrode/electrolyte interface area, thus resulting in improved electrochemical
performance. For the proposed YSC, a high areal-specific capacitance of 74.0mFcm
2 and a desirable energy density of 7.5MUWhcm-2 are achieved. The flexibility of
the YSC demonstrates that it is suitable for the integration as flexible power
sources in wearable electronic textiles.
PMID- 28504172
TI - Development of polylactic acid nanocomposite films reinforced with cellulose
nanocrystals derived from coffee silverskin.
AB - Bio-nanocomposite films based on polylactic acid (PLA) matrix reinforced with
cellulose nanocrystals (CNCs) were developed using a twin-screw extruder. The
CNCs were extracted from coffee silverskin (CS), which is a by-product of the
coffee roasting process. They were extracted by alkali treatment followed by
sulfuric acid hydrolysis. They were used as reinforcing agents to obtain PLA/CNC
nanocomposites by addition at different concentrations (1%, 3%, and 5% CNCs).
Morphological, tensile, and barrier properties of the bio-nanocomposites were
analyzed. The tensile strength and Young's modulus increased with both 1% and 3%
CNCs. The water vapor permeability decreased gradually with increasing addition
of CNCs up to 3% and good oxygen barrier properties were found for all
nanocomposites. These results suggest that CNCs from CS can improve the physical
properties of PLA-based biopolymer film. The developed PLA/CNC bio-nanocomposite
films can potentially be used for biopolymer materials with enhanced barrier and
mechanical properties.
PMID- 28504174
TI - Pineapple peel carboxymethyl cellulose/polyvinyl alcohol/mesoporous silica SBA-15
hydrogel composites for papain immobilization.
AB - Hydrogel composites based on pineapple peel carboxymethyl cellulose, polyvinyl
alcohol and mesoporous silica SBA-15 were synthesized by an eco-friendly method
of repeated freeze-thaw cycles for the application of papain immobilization. The
experiment was optimized to obtain an efficient papain immobilization carrier.
Simultaneously the immobilization conditions, including enzyme concentration, pH,
crosslinker concentration and cross-linking time were optimized. The immobilized
papain had maximum activity at low reaction temperature of 40 degrees C and
showed pH-sensitivity by exhibiting a rapid decrease of activity within a narrow
range from pH 7.0 to pH 7.5. Compared with the free papain, the immobilized
papain revealed enhanced pH, thermal and storage stability. After 2h incubation
at 80 degrees C, the immobilized papain retained 56% of its initial activity
while the free papain only retained 16%. After 10days of storage, 79% of the
initial activity was retained for the immobilized papain while only 27% for the
free papain.
PMID- 28504175
TI - Sulfoethylated nanofibrillated cellulose: Production and properties.
AB - Sulfoethylated nanofibrillated cellulose (NFCSulf) was produced by an
industrially relevant process. The properties of the NFCSulf were compared with
those of carboxymethylated nanofibrillated cellulose (NFCCarb), which has been
identified as an attractive NFC for several industrial applications. The
investigations revealed that NFCSulf is characterized by a higher degree of
fibrillation and has superior redispersion properties. Furthermore, NFCSulf
displays higher stability in varying pH values as compared to NFCCarb. Hence,
NFCSulf may be a more attractive alternative than NFCCarb in applications such as
rheological modifiers or adsorbing components in personal care products, in which
the performance of NFC must remain unaffected in varying ambient conditions. The
superior properties of NFCSulf compared to NFCCarb were proposed to be due to the
combination of the unique chemical characteristics of the sulfoethylated reagent,
and the larger size of the sulfonate group compared to the carboxymethyl group.
PMID- 28504176
TI - Eco-friendly soluble soybean polysaccharide/nanoclay Na+ bionanocomposite:
Properties and characterization.
AB - The impact of montmorillonite (MMT) as a nanofiller at different concentrations
(5, 10, 15wt.%) on the physicochemical and functional properties of nanocomposite
film based on soluble soybean polysaccharide (SSPS) was investigated. The results
showed that an increase in MMT concentration was accompanied by a decrease in
water solubility, thickness, and elongation at break. Furthermore, tensile
strength increased when MMT concentration was increased to 10wt.%. Atomic force
and scanning electron micrographs showed a significant agglomeration at MMT
15wt.%. With added MMT, the level of whiteness, greenness, and yellowness of SSPS
film increased (P<0.05). Dynamic mechanical thermal analysis indicated that the
storage modulus of nanocomposites increased when the MMT was increased to 10wt.%.
Furthermore, Fourier transform infrared spectrophotometry demonstrated that no
considerable changes occurred in the functional groups of the SSPS when MMT was
added. Antimicrobial tests revealed that antibacterial and anti-mold activities
were unlikely from reinforced nanocomposites.
PMID- 28504177
TI - Corrigendum to "Biosynthesis of agar in red seaweeds: A review" [Carbohydr.
Polym. 164 (2017) 23-30].
PMID- 28504178
TI - Tetramethylguanidine-based gels and colloids of cellulose.
AB - Novel and stable gels of cellulose were produced. These gels are prepared at room
temperature by combination of cellulose and tetramethylguanidine (TMG) in
different ratios (1:1, 1:2, 1:3 in equivalents of alcohol groups of cellulose per
number of molecules of TMG). Detailed NMR, SEM, rheological and XRD studies of
these gels were carried out. The concentration of cellulose in the gel,
temperature, frequency of oscillation and shear rate were used as variables in
order to understand the fundamentals and optimize operational conditions,
considering their possible use as matrices for CO2 capture. Cellulose recovery
from a specific gel was performed using ethanol as precipitating agent, leading
to a lower crystallinity, which permits to consider this polymer in further
studies associated to physical/chemical modification of cellulose.
PMID- 28504180
TI - The glycogen of Galdieria sulphuraria as alternative to starch for the production
of slowly digestible and resistant glucose polymers.
AB - Highly branched glucose polymers produced from starch are applied in various
products, such as peritoneal dialysis solutions and sports drinks. Due to its
insoluble, granular nature, the use of native starch as substrate requires an
energy consuming pre-treatment to achieve solubilization at the expense of
process costs. Glycogen, like starch, is also a natural glucose polymer that
shows more favorable features, since it is readily soluble in cold water and more
accessible by enzymes. The extremophilic red microalga Galdieria sulphuraria
accumulates large amounts of a small, highly branched glycogen that could
represent a good alternative to starch as substrate for the production of highly
branched glucose polymers. In the present work, we analyzed the structure
properties relationship of this glycogen in its native form and after treatment
with amyloglucosidase and compared it to highly branched polymers produced from
potato starch. Glycogen showed lower susceptibility to digestive enzymes and
significantly decreased viscosity in solution compared to polymers derived from
starch, properties conferred by its shorter side chains and higher branch
density. The action of amyloglucosidase on native glycogen was somewhat limited
due to the high branch density but resulted in the production of a hyperbranched
polymer that was virtually resistant to digestive enzymes.
PMID- 28504179
TI - Immunomodulatory effects of xanthan gum in LPS-stimulated RAW 264.7 macrophages.
AB - In this study, we evaluated the immunomodulatory effects of xanthan gum (XG) in
RAW264.7 macrophages and the underlying molecular mechanisms. We used scanning
electron microscopy (SEM) to analyze the morphology of XG-treated RAW264.7 cells
with and without lipopolysaccharide (LPS) stimulation and investigated the
subsequent effects on nitric oxide (NO), interleukin-1beta (IL-1beta),
interleukin-6 (IL-6), tumor necrosis factor (TNF-alpha), inducible nitric oxide
synthase (iNOS), and cyclooxygenase-2 (COX-2) levels in LPS-activated mouse
RAW264.7 macrophages. We also analyzed the binding affinity of XG to Toll-like
receptor 4 (TLR4) with surface plasmon resonance (SPR) analysis and observed that
XG decreased NO, IL-6 and TNF-alpha secretion into the culture medium and iNOS
and COX-2 protein levels induced by LPS. This study reveals a two-way
immunomodulatory effect of XG on inflammatory mediators in RAW264.7 macrophages
that may involve the TLR4 signal pathway, providing a pharmacological basis for
the use of XG in the control of inflammatory disorders.
PMID- 28504181
TI - Preparation of N, N, N-trimethyl chitosan via a novel approach using dimethyl
carbonate.
AB - N,N,N-trimehtyl chitosan (TMC) is a water-soluble derivate of chitosan, which has
been widely used as a biomedical material due to its excellent biocompatibility,
biodegradability and bacterial properties. To date, TMC can only be prepared by
the quaternization of chitosan using alkyl halide or dimethyl sulfate. However,
alkyl halide and dimethyl sulfate are highly toxic, cancerigenic for humans, and
harmful to the environment. This paper puts forward a novel approach to preparing
TMC using dimethyl carbonate as a methylation reagent in an ionic liquid. The as
synthesized O-methyl-free TMC was characterized using NMR, FTIR, XRD and TG
analyses. The results showed that TMC with a degree of quaternization of 9.11%
was successfully obtained and the crystallinity of chitosan decreased with the
increasing degree of N-methylation, the thermal stability of TMC was lower than
that of chitosan. Furthermore, the effects of the dose of ionic liquid and
dimethyl carbonate were disscussed.
PMID- 28504183
TI - Enzymic degradation of hydroxyethyl cellulose and analysis of the substitution
pattern along the polysaccharide chain.
AB - The enzymatic degradation behavior of hydroxyethyl cellulose (HEC) samples with
different molar substitutions (MS) values was investigated. The changes in the
molecular structure of HEC treated with enzymatic approach in comparison to the
native HEC were studied through nuclear magnetic resonance (NMR), fourier
transform infrared spectra (FTIR), X-ray diffraction (XRD) and scanning electron
microscopy (SEM) techniques and kinetics of degradation was studied by
viscometry. The cleavage of HEC chains could be observed from FTIR and kinetics
results. Moreover, reduce in molecular weight (Mw) of polymer and liberated
glucose concentration was investigated by gel permeation chromatography (GPC)
analysis during enzymatic degradation. And all these results indicated that HEC
with lower MS is more susceptible to degrade and provided a better understanding
of the mechanism operating during enzymatic hydrolysis of HEC by cellulases.
Furthermore, by complete degradation and quantification of liberated glucose, the
substitution index (SI) and the distribution of substituents along the HEC chain
were investigated. The results suggested that the HEC samples differed in
hydroxyethyl molar substitutions (MS) and possible distribution of the
hydroxyethyl groups. Impressively, our efforts established a facile analytical
method for the elucidation of the distribution of substituents along the HEC
chain.
PMID- 28504182
TI - Oil/water interfaces of guar gum-based biopolymer hydrogels and application to
their separation.
AB - Oily wastewater treatment has become a significant research subject due to
potential environmental related applications, e.g., oil spill remedy process. In
this paper, a natural polymer based hydrogel, prepared from guar gum (GG) and
metaborate, was coated onto a stainless steel mesh, and the as-prepared hydrogel
coated material was applied for oil/water separation. The strong hydrophilic GG
hydrogel imparted excellent underwater oleophobicity and ultra-low oil adhesion.
The results proved that the as-prepared GG hydrogel-coated material possessed
excellent self-cleaning property and high oil/water separation efficiency.
PMID- 28504185
TI - Comments on the finding of right non recurrent laryngeal nerve during
thyroidectomy.
PMID- 28504184
TI - Lessons from healthcare utilization in children with obstructive sleep apnoea
syndrome.
AB - INTRODUCTION AND OBJECTIVES: Paediatric Obstructive Sleep Apnoea-Hypopnoea
Syndrome (OSAS) is a multisystemic condition affecting child's health status that
may be investigated analyzing demand for healthcare. OBJECTIVE: to quantify the
frequency of medical consultations in children with OSAS over a 5-year period,
compared to a healthy population. METHODS: A longitudinal, case-control,
ambispective study was conducted at a hospital pertaining to the national public
health system. 69 consecutive children referred for OSAS were recruited with no
diseases other than OSAS so that healthcare demand was purely attributed to this
condition. Matched healthy control children were selected to compare these data.
Data regarding frequency of the medical consultations were obtained over 5 years:
the year of the treatment ("Year0"), 1 and 2 years before ("Year -1" and "Year
2" respectively), and 1 and 2 years after treatment ("Year+1" and "Year+2")
RESULTS: Frequentation Index (FI), as ratio between the use of health services by
OSAS children and healthy controls was 1.89 during Year-2, and 2.15 during Year-1
(P<.05). Treatment diminishes utilization, with FI of 159 during year+1 and 1.72
during year+2 (P<.05). The main causes of attendance were otolaryngological and
pneumological diseases, improving after treatment. CONCLUSIONS: Children
suffering from OSAS demand more healthcare services, at least 2 years before
treatment, implying that the disease could be present years before we manage it.
Therapeutic actions improve healthcare services utilization, although remain
higher than for controls, which suggests OSAS sequelae or residual disease.
PMID- 28504186
TI - Alagille's syndrome: Hypoplasia of posterior semicircular canals.
PMID- 28504187
TI - Transoral oropharyngeal resection classification: Proposal of the SCORL working
group.
AB - INTRODUCTION AND GOALS: There has been a very significant increase in the use of
minimally invasive surgery has in the last decade. In order to provide a common
language after transoral surgery of the oropharynx, a system for classifying
resections has been created in this area, regardless of the instrumentation used.
METHODS: From the Oncology Working Group of the Catalan Society of
Otorhinolaryngology, a proposal for classification based on a topographical
division of the different areas of the oropharynx is presented, as also based on
the invasion of the related structures according to the anatomical routes of
extension of these tumours. RESULTS: The classification starts using the letter D
or I according to laterality either right (D) or left (I). The number of the
resected area is then placed. This numbering defines the zones beginning at the
cranial level where area I would be the soft palate, lateral area II in the
tonsillar area, area III in the tongue base, area IV in the glossoepiglottic
folds, epiglottis and pharyngoepiglottic folds, area V posterior oropharyngeal
wall and VI the retromolar trigone. The suffix p is added if the resection deeply
affects the submucosal plane of the compromised area. The different proposed
areas would, in theory, have different functional implications. CONCLUSIONS:
Proposal for a system of classification by area to definedifferent types of
transoral surgery of the oropharynx, and enable as sharing of results and helps
in teaching this type of technique.
PMID- 28504188
TI - Discrepancy between clinical and pathological neck staging in oral cavity
carcinomas.
AB - INTRODUCTION: The presence of cervical lymph node metastases in patients with
oral cavity squamous cell carcinoma reduces survival by up to 50%. OBJECTIVE: The
aims of this study are to assess the accuracy of clinical N staging versus
pathological N staging and its impact on survival in order to identify predictive
factors associated with the presence of occult neck metastases. METHODS: Outcomes
of 105 patients with oral cavity squamous cell carcinoma who underwent surgical
treatment of the primary tumor and neck were retrospectively evaluated. RESULTS:
For pN0 and pN+ patients 5-year overall survival was respectively 53% and 27%;
disease specific survival was 66% for pN0 and 33% for pN+. Patients with clinical
negative lymph nodes were pathologically upstaged in 62% of cases. Disease
specific survival according to staging discrepancy had statistically significant
impact on survival (p=0.009). CONCLUSION: Clinical staging usually underestimates
the presence of nodal disease. Neck dissection should be performed in cN0 oral
cavity squamous cell carcinoma.
PMID- 28504189
TI - Ezrin Ser66 phosphorylation regulates invasion and metastasis of esophageal
squamous cell carcinoma cells by mediating filopodia formation.
AB - BACKGROUND: Ezrin, links the plasma membrane to the actin cytoskeleton, and plays
an important role in the development and progression of human esophageal squamous
cell carcinoma (ESCC). However, the roles of ezrin S66 phosphorylation in
tumorigenesis of ESCC remain unclear. METHODS: Distribution of ezrin in membrane
and cytosol fractions was examined by analysis of detergent-soluble/-insoluble
fractions and cytosol/membrane fractionation. Both immunofluorescence and live
imaging were used to explore the role of ezrin S66 phosphorylation in the
behavior of ezrin and actin in cell filopodia. Cell proliferation, migration and
invasion of ESCC cells were investigated by proliferation and migration assays,
respectively. Tumorigenesis, local invasion and metastasis were assessed in a
nude mouse model of regional lymph node metastasis. RESULTS: Ezrin S66
phosphorylation enhanced the recruitment of ezrin to the membrane in ESCC cells.
Additionally, non-phosphorylatable ezrin (S66A) significantly prevented filopodia
formation, as well as caused a reduction in the number, length and lifetime of
filopodia. Moreover, functional experiments revealed that expression of non
phosphorylatable ezrin (S66A) markedly suppressed migration and invasion but not
proliferation of ESCC cells in vitro, and attenuated local invasion and regional
lymph node metastasis, but not primary tumor growth of ESCC cells in vivo.
CONCLUSION: Ezrin S66 phosphorylation enhances filopodia formation, contributing
to the regulation of invasion and metastasis of esophageal squamous cell
carcinoma cells.
PMID- 28504190
TI - Expression and alternative splicing of the cyclin-dependent kinase inhibitor-3
gene in human cancer.
AB - The cyclin-dependent kinase inhibitor-3 (CDKN3) gene encodes a dual-specificity
protein tyrosine phosphatase that dephosphorylates CDK1/CDK2 and other proteins.
CDKN3 is often overexpressed in human cancer, and this overexpression correlates
with reduced survival in several types of cancer. CDKN3 transcript variants and
mutations have also been reported. The mechanism of CDKN3 overexpression and the
role of CDKN3 transcript variants in human cancer are not entirely clear. Here,
we review the literature and provide additional data to assess the correlation of
CDKN3 expression with patient survival. Besides the full-length CDKN3 encoding
transcript and a major transcript that skips exon 2 express in normal and cancer
cells, minor aberrant transcript variants have been reported. Aberrant CDKN3
transcripts were postulated to encode dominant-negative inhibitors of CDKN3 as an
explanation for overexpression of the perceived tumor suppressor gene in human
cancer. However, while CDKN3 is often overexpressed in human cancer, aberrant
CDKN3 transcripts occur infrequently and at lower levels. CDKN3 mutations and
copy number alternation are rare in human cancer, implying that neither loss of
CDKN3 activity nor constitutive gain of CDKN3 expression offer an advantage to
tumorigenesis. Recently, it was found that CDKN3 transcript and protein levels
fluctuate during the cell cycle, peaking in mitosis. Given that rapidly growing
tumors have more mitotic cells, the high level of mitotic CDKN3 expression is the
most plausible mechanism of frequent CDKN3 overexpression in human cancer. This
finding clarifies the mechanism of CDKN3 overexpression in human cancer and
questions the view of CDKN3 as a tumor suppressor.
PMID- 28504192
TI - Correlates of protection for enteric vaccines.
AB - An immunological Correlate of Protection (CoP) is an immune response that is
statistically interrelated with protection. Identification of CoPs for enteric
vaccines would help design studies to improve vaccine performance of licensed
vaccines in low income settings, and would facilitate the testing of future
vaccines in development that might be more affordable. CoPs are lacking today for
most existing and investigational enteric vaccines. In order to share the latest
information on CoPs for enteric vaccines and to discuss novel approaches to
correlate mucosal immune responses in humans with protection, the Foundation
Merieux organized an international conference of experts where potential CoPs for
vaccines were examined using case-studies for both bacterial and viral enteric
pathogens. Experts on the panel concluded that to date, all established enteric
vaccine CoPs, such as those for hepatitis A, Vi typhoid and poliovirus vaccines,
are based on serological immune responses even though these may poorly reflect
the relevant gut immune responses or predict protective efficacy. Known CoPs for
cholera, norovirus and rotavirus could be considered as acceptable for
comparisons of similarly composed vaccines while more work is still needed to
establish CoPs for the remaining enteric pathogens and their candidate vaccines.
Novel approaches to correlate human mucosal immune responses with protection
include the investigation of gut-originating antibody-secreting cells (ASCs), B
memory cells and follicular helper T cells from samples of peripheral blood
during their recirculation.
PMID- 28504193
TI - Global economic evaluations of rotavirus vaccines: A systematic review.
AB - INTRODUCTION: World Health Organization (WHO) recommends Rotavirus vaccines to
prevent and control rotavirus infections. Economic evaluations (EE) have been
considered to support decision making of national policy. Summarizing global
experience of the economic value of rotavirus vaccines is crucial in order to
encourage global WHO recommendations for vaccine uptake. Therefore, a systematic
review of economic evaluations of rotavirus vaccine was conducted. METHODS: We
searched Medline, Embase, NHS EED, EconLit, CEA Registry, SciELO, LILACS, CABI
Global Health Database, Popline, World Bank - e-Library, and WHOLIS. Full
economic evaluations studies, published from inception to November 2015,
evaluating Rotavirus vaccines preventing Rotavirus infections were included. The
methods, assumptions, results and conclusions of the included studies were
extracted and appraised using WHO guide for standardization of EE of immunization
programs. RESULTS: 104 relevant studies were included. The majority of studies
were conducted in high-income countries. Cost-utility analysis was mostly
reported in many studies using incremental cost-effectiveness ratio per DALY
averted or QALY gained. Incremental cost per QALY gained was used in many studies
from high-income countries. Mass routine vaccination against rotavirus provided
the ICERs ranging from cost-saving to highly cost-effective in comparison to no
vaccination among low-income countries. Among middle-income countries,
vaccination offered the ICERs ranging from cost-saving to cost-effective. Due to
low- or no subsidized price of rotavirus vaccines from external funders, being
not cost-effective was reported in some high-income settings. CONCLUSION: Mass
vaccination against rotavirus was generally found to be cost-effective,
particularly in low- and middle-income settings according to the external
subsidization of vaccine price. On the other hand, it may not be a cost-effective
intervention at market price in some high-income settings. This systematic review
provides supporting information to health policy-makers and health professionals
when considering rotavirus vaccination as a national program.
PMID- 28504191
TI - Lethal factor antibodies contribute to lethal toxin neutralization in recipients
of anthrax vaccine precipitated.
AB - A major difference between two currently licensed anthrax vaccines is presence
(United Kingdom Anthrax Vaccine Precipitated, AVP) or absence (United States
Anthrax Vaccine Adsorbed, AVA) of quantifiable amounts of the Lethal Toxin (LT)
component Lethal Factor (LF). The primary immunogen in both vaccine formulations
is Protective Antigen (PA), and LT-neutralizing antibodies directed to PA are an
accepted correlate of vaccine efficacy; however, vaccination studies in animal
models have demonstrated that LF antibodies can be protective. In this report we
compared humoral immune responses in cohorts of AVP (n=39) and AVA recipients
(n=78) matched 1:2 for number of vaccinations and time post-vaccination, and
evaluated whether the LF response contributes to LT neutralization in human
recipients of AVP. PA response rates (>=95%) and PA IgG concentrations were
similar in both groups; however, AVP recipients exhibited higher LT
neutralization ED50 values (AVP: 1464.0+/-214.7, AVA: 544.9+/-83.2, p<0.0001) and
had higher rates of LF IgG positivity (95%) compared to matched AVA vaccinees
(1%). Multiple regression analysis revealed that LF IgG makes an independent and
additive contribution to the LT neutralization response in the AVP group.
Affinity purified LF antibodies from two independent AVP recipients neutralized
LT and bound to LF Domain 1, confirming contribution of LF antibodies to LT
neutralization. This study documents the benefit of including an LF component to
PA-based anthrax vaccines.
PMID- 28504195
TI - FGF18 protects against 6-hydroxydopamine-induced nigrostriatal damage in a rat
model of Parkinson's disease.
AB - Dopaminergic neuronal injury in the substantia nigra (SN) is a pathological
hallmark of Parkinson's disease (PD). However, the underlying mechanism of this
injury remains elusive. Since fibroblast growth factor 18 (FGF18) is involved in
midbrain development and has been reported to protect neurons from ischemic
injury, we investigated whether FGF18 exerted a protective effect on dopaminergic
neurons in the SN. In vitro data showed that FGF18 significantly ameliorated the
neurotoxicity of 6-hydroxydopamine (6-OHDA) through the AKT/GSK3beta signaling
pathway. Further study of the 6-OHDA-induced PD rat model indicated that FGF18
improved the behavioral dysfunction in PD rats and reduced the tyrosine
hydroxylase (TH)-positive neuronal loss in the SN. In addition, 6-OHDA induced a
loss of TH-positive fibers that was reversed by pretreatment with FGF18. Taken
together, these data suggest that FGF18 plays a protective role against
parkinsonian neurodegeneration in the nigrostriatal system in a 6-OHDA-induced PD
rat model and that further drug discovery based on FGF18 has a potential role for
PD therapy.
PMID- 28504196
TI - Human subthalamic nucleus - Automatic auditory change detection as a basis for
action selection.
AB - The subthalamic nucleus (STN) shapes motor behavior and is important for the
initiation and termination of movements. Here we ask whether the STN takes
aggregated sensory information into account, in order to exert this function. To
this end, local field potentials (LFP) were recorded in eight patients suffering
from Parkinson's disease and receiving deep-brain stimulation of the STN
bilaterally. Bipolar recordings were obtained postoperatively from the
externalized electrode leads. Patients were passively exposed to trains of
auditory stimuli containing global deviants, local deviants or combined
global/local deviants. The surface event-related potentials of the Parkinson's
patients as well as those of 19 age-matched healthy controls were characterized
by a mismatch negativity (MMN) that was most pronounced for the global/local
double deviants and less prominent for the other deviant conditions. The left and
right STN LFPs similarly were modulated by stimulus deviance starting at about
100ms post-stimulus onset. The MMN has been viewed as an index of an automatic
auditory change detection system, more recently phrased in terms of predictive
coding theory, which prepares the organism for attention shifts and for action.
The LFP-data from the STN clearly demonstrate that the STN receives information
on stimulus deviance, possibly as a means to bias the system to interrupt ongoing
and to allow alternative actions.
PMID- 28504194
TI - Vaccination with recombinant paramyosin in Montanide ISA206 protects against
Schistosoma japonicum infection in water buffalo.
AB - BACKGROUND: Schistosomiasis japonica is a zoonosis and presents significant
public health problems in China and the Philippines. Vaccines targeting domestic
animals constitute attractive control measures. METHODS: We conducted three
vaccine trials to evaluate the protective efficacy of recombinant full-length
paramyosin (rSj97) in water buffalo. Animals were immunized with 3 doses of rSj97
adjuvanted with ISA206 at 250MUg/dose or 500MUg/dose at 4wk intervals before
challenge with 1000 Schistosoma japonicum cercariae. The primary outcome was worm
burden assessed by portal perfusion 8-10weeks post challenge. Safety measures
included weight, temperature, body condition score, hemogram and routine assays
for hepatic and renal function. RESULTS: The three-dose regimen was well
tolerated in all three trials. In the first trial, vaccinated buffalo had 51.5%
lower worm burden post challenge compared to controls. In the second trial,
buffalo immunized with 500MUg/dose of rSj97 had 57.8% lower worm burden compared
to controls (p=0.026). A similar but not significant reduction (60.9%) was
observed with animals administered with 250ug rSj97/dose. In the third trial,
buffalo immunized with a 500MUg/dose of rSj97 had 57.8% lower worm burden
compared to controls (p=0.014). CONCLUSIONS: These findings indicated that rSj97
is a safe and promising vaccine candidate for schistosomiasis japonica in water
buffalo.
PMID- 28504197
TI - Intravenous injection of umbilical cord-derived mesenchymal stromal cells
attenuates reactive gliosis and hypomyelination in a neonatal intraventricular
hemorrhage model.
AB - Intraventricular hemorrhage (IVH) is a frequent complication of preterm newborns,
resulting in cerebral palsy and cognitive handicap as well as hypoxic ischemic
encephalopathy and periventricular leukomalacia. In this study, we investigated
the restorative effect on neonatal IVH by umbilical cord-derived mesenchymal
stromal cells (UC-MSCs) cultured in serum-free medium (RM medium) for clinical
application. UC-MSCs were cultured with alphaMEM medium supplemented with FBS or
RM. A neonatal IVH mouse model at postnatal day 5 was generated by
intraventricular injection of autologous blood, and mice were intravenously
administered 1*105 UC-MSCs two days after IVH. Brain magnetic resonance imaging
was performed at postnatal day 15, 22 and neurological behavioral measurements
were performed at postnatal day 23, accompanied by histopathological analysis and
cytokine bead assays in serum after IVH with or without UC-MSCs. Both UC-MSCs
cultured with alphaMEM and RM met the criteria of MSCs and improved behavioral
outcome of IVH mice. Moreover the RM group exhibited significant behavioral
improvement compared to the control group. Histopathological analysis revealed UC
MSCs cultured with RM significantly attenuated periventricular reactive gliosis,
hypomyelination, and periventricular cell death observed after IVH. Furthermore,
human brain-derived neurotrophic factor and hepatocyte growth factor were
elevated in the serum, cerebrospinal fluid and brain tissue of neonatal IVH model
mice 24h after UC-MSCs administration. These results suggest UC-MSCs attenuate
neonatal IVH by protecting gliosis and apoptosis of the injured brain, and
intravenous injection of UC-MSCs cultured in RM may be feasible for neonatal IVH
in clinic.
PMID- 28504198
TI - Rapamycin suppresses Abeta25-35- or LPS-induced neuronal inflammation via
modulation of NF-kappaB signaling.
AB - Rapamycin (RAPA), an inhibitor of mammalian target of rapamycin (mTOR), exhibits
a high neuroprotective action against neurodegenerative diseases in mouse models.
Since neuroinflammation has been shown to be involved in Alzheimer's disease (AD)
development and progression, the aim of this study was to examine the anti
inflammatory role of RAPA in AD in vivo and in vitro, and investigate the
underlying mechanisms. We found that amyloid-beta (Abeta) induced neuronal
inflammation and a remarkable increase in mTOR activity in in-vivo and in-vitro
models of inflammation, suggesting the critical role of mTOR signaling in
neuronal inflammation. In addition, administration of RAPA was found to down
regulate mTOR, p-mTOR, Nuclear factor kappa B (NF-kappaB) p65, p-p65, TNF-alpha,
IL-1beta and Bax protein expression in Abeta25-35- or lipopolysaccharides (LPS)
treated mice and cultured Neuro-2a (N2a) cells. Moreover, RAPA disrupted Abeta25
35-induced nuclear translocation of mTOR and NF-kappaB. Our findings indicate
that RAPA inhibits Abeta25-35- or LPS-induced neuronal inflammation through
suppressing mTOR signaling and reducing nuclear import of NF-kappaB.
PMID- 28504199
TI - Lithopedion developed in a non-communicating rudimentary uterine horn: CT
features.
PMID- 28504200
TI - Portal invasion: An exceptional complication of hepatic hydatid disease.
PMID- 28504201
TI - Cilia - The sensory antennae in the eye.
AB - Cilia are hair-like projections found on almost all cells in the human body.
Originally believed to function merely in motility, the function of solitary non
motile (primary) cilia was long overlooked. Recent research has demonstrated that
primary cilia function as signalling hubs that sense environmental cues and are
pivotal for organ development and function, tissue hoemoestasis, and maintenance
of human health. Cilia share a common anatomy and their diverse functional
features are achieved by evolutionarily conserved functional modules, organized
into sub-compartments. Defects in these functional modules are responsible for a
rapidly growing list of human diseases collectively termed ciliopathies. Ocular
pathogenesis is common in virtually all classes of syndromic ciliopathies, and
disruptions in cilia genes have been found to be causative in a growing number of
non-syndromic retinal dystrophies. This review will address what is currently
known about cilia contribution to visual function. We will focus on the molecular
and cellular functions of ciliary proteins and their role in the photoreceptor
sensory cilia and their visual phenotypes. We also highlight other ciliated cell
types in tissues of the eye (e.g. lens, RPE and Muller glia cells) discussing
their possible contribution to disease progression. Progress in basic research on
the cilia function in the eye is paving the way for therapeutic options for
retinal ciliopathies. In the final section we describe the latest advancements in
gene therapy, read-through of non-sense mutations and stem cell therapy, all
being adopted to treat cilia dysfunction in the retina.
PMID- 28504202
TI - Corrigendum to "The rod-driven a-wave of the dark-adapted mammalian
electroretinogram" [Progress in Retinal and Eye Research, volume 39, March 2014,
pages 1-22].
PMID- 28504203
TI - Internal validation of STRmixTM for the interpretation of single source and mixed
DNA profiles.
AB - The interpretation of DNA evidence can entail analysis of challenging STR typing
results. Genotypes inferred from low quality or quantity specimens, or mixed DNA
samples originating from multiple contributors, can result in weak or
inconclusive match probabilities when a binary interpretation method and
necessary thresholds (such as a stochastic threshold) are employed. Probabilistic
genotyping approaches, such as fully continuous methods that incorporate
empirically determined biological parameter models, enable usage of more of the
profile information and reduce subjectivity in interpretation. As a result,
software-based probabilistic analyses tend to produce more consistent and more
informative results regarding potential contributors to DNA evidence. Studies to
assess and internally validate the probabilistic genotyping software STRmixTM for
casework usage at the Federal Bureau of Investigation Laboratory were conducted
using lab-specific parameters and more than 300 single-source and mixed
contributor profiles. Simulated forensic specimens, including constructed
mixtures that included DNA from two to five donors across a broad range of
template amounts and contributor proportions, were used to examine the
sensitivity and specificity of the system via more than 60,000 tests comparing
hundreds of known contributors and non-contributors to the specimens. Conditioned
analyses, concurrent interpretation of amplification replicates, and application
of an incorrect contributor number were also performed to further investigate
software performance and probe the limitations of the system. In addition, the
results from manual and probabilistic interpretation of both prepared and
evidentiary mixtures were compared. The findings support that STRmixTM is
sufficiently robust for implementation in forensic laboratories, offering
numerous advantages over historical methods of DNA profile analysis and greater
statistical power for the estimation of evidentiary weight, and can be used
reliably in human identification testing. With few exceptions, likelihood ratio
results reflected intuitively correct estimates of the weight of the genotype
possibilities and known contributor genotypes. This comprehensive evaluation
provides a model in accordance with SWGDAM recommendations for internal
validation of a probabilistic genotyping system for DNA evidence interpretation.
PMID- 28504204
TI - Elastic staining-a rejuvenated method to reassess prognosis and serosal invasion
in patients with pT3N0M0 gastric cancer.
AB - Prognosis of pT3N0M0 gastric cancer (GC) varies greatly, though the major factor
conferring poor prognosis is unclear. Subserosal elastic lamina invasion (ELI+)
is closely associated with poor outcomes in pT3 colorectal cancer, but related
research on GC is unavailable. This study aimed to identify the influence of ELI+
on the prognosis of patients with pT3N0M0 GC and its relationship with serosal
invasion using elastic staining. We retrospectively reviewed 94 and 28 patients
with pT3N0M0 and pT4aN0M0 GC who underwent gastrectomy between 1994 and 2005. For
the former, one section with invasion depth closest to the peritoneal surface and
one corresponding paraffin block for each specimen were selected for conventional
elastic staining to assess the relationship between ELI+ and patients' clinical
characteristics and survival. pT3N0M0 GC specimens were divided into 3 groups
based on staining results: ELI+ (N=51), non-invasion (N=31), and unidentified
(N=12). ELI+ was closely related to recurrence and lymphovascular invasion. Five
year disease-free (DFS) (46%) and overall (OS) (36%) survival rates were
significantly lower in the ELI+ than in the non-invasion or unidentified groups
(P<.0001); no obvious difference was found between the ELI+ and pT4aN0M0 groups
(P=.25). Multivariate analysis showed ELI+ and recurrence as independent
prognostic factors for DFS in pT3 GC patients. In conclusion, elastic staining is
an effective and highly feasible method for predicting prognosis and evaluating
the serosal invasion depth of pT3 GC. pT3 GC accompanied with ELI+ is an obvious
adverse prognostic factor and could be considered a treatment for pT4a GC.
PMID- 28504206
TI - BRAF V600E mutation in pediatric intracranial and cranial juvenile
xanthogranuloma.
AB - Juvenile xanthogranuloma (JXG) is a cutaneous form of non-Langerhans cell
histiocytosis, primarily affecting children. The lesion is presumed to originate
from either macrophages or dermal dendritic cells. JXG can rarely present as an
isolated intracranial lesion and, in contrast to the dismal outcome of patients
with systemic disease, cranial JXG has been shown to carry a more favorable
prognosis. Here, we report for the first time 3 pediatric cases of JXG with a
BRAF V600E mutation, 2 with intracranial lesions and 1 with cranial lesions.
Although these intracranial/cranial lesions have been referred to as JXG, they
likely differ from cutaneous JXG in both the clinical features and BRAF status.
It may be more appropriate to classify intracranial/cranial JXG in the same group
as Langerhans cell histiocytosis and Erdheim-Chester disease, which also have a
BRAF V600E mutation. Further study of BRAF status in a larger series of JXG is
warranted.
PMID- 28504205
TI - Comparison of clinicopathologic characteristics of gastric follicular lymphomas
and duodenal follicular lymphomas.
AB - We compared the incidence, esophagogastroduodenoscopy (EGD) findings, and
histopathologic characteristics of gastric and duodenal follicular lymphomas
(FL). Of 626 FL cases, primary gastric FL and secondary gastric involvement of FL
were observed in 1% and 5% of the cases, respectively, which were lower
incidences than duodenal FL (10% and 9%, respectively). Gastric FL usually
appeared as submucosal tumors (primary, 71%; secondary, 79%), whereas duodenal
FL, as granular lesions (primary, 92%: secondary, 87%). In the granular duodenal
lesions, the neoplastic follicles were located sparsely on the muscularis mucosa
and could be found between villi, whereas in the stomach, similar lesions were
hidden within the lamina propria, and only larger lesions such as submucosal
tumors could be detected on the mucosal surface. The differences in the
incidences and EGD findings were considered to be associated with structural
differences of the lamina propria. Typical FL features: grades 1-2 histology,
follicularity, and CD10+ and/or BCL6+ and BCL2+ were usually observed in all
primary and secondary gastric and duodenal FL. Gastroduodenal and bone marrow
involvement were found in 12% and 33% of the cases, respectively, and there was
no significant correlation between them (P=.095). Twenty-nine cases (5%) were up
staged by gastroduodenal-positive results. In conclusion, the histopathology of
gastric FL was similar to that of duodenal and nodal FL; the differences in the
incidence and EGD findings between gastric and duodenal FL were considered to be
associated with structural difference of the lamina propria, and EGD was useful
as a staging procedure.
PMID- 28504207
TI - A novel fusion of HNRNPA1-ALK in inflammatory myofibroblastic tumor of urinary
bladder.
AB - Here, we report an inflammatory myofibroblastic tumor (IMT) of the urinary
bladder with a novel HNRNPA1-ALK fusion. To the best of our knowledge, this is
the first case of a tumor with HNRNPA1-ALK fusion. A 42-year-old Japanese man
underwent total cystectomy because of an invasive urinary bladder tumor. Grossly,
the tumor had invaded the peribladder fat tissue. Histologically, it comprised
spindle neoplastic cells with intermingled inflammatory cells.
Immunohistochemically, it was positive for ALK, SMA, desmin, cytokeratin, and
vimentin, consistent with the immunohistochemical characteristics of IMTs.
Fluorescence in situ hybridization demonstrated an ALK split, and the presence of
HNRNPA1-ALK was revealed by RNA sequencing. We identified a novel transcript
fusion of exon 2 of HNRNPA1 and exon 18 of ALK, resulting in ALK protein
overexpression. These findings provide useful information on the biology and
tumorigenesis of IMTs, thus facilitating the development of molecular-targeted
therapeutics.
PMID- 28504208
TI - PTEN loss and p27 loss differ among morphologic patterns of prostate cancer,
including cribriform.
AB - The presence and extent of cribriform pattern of prostate cancer portend
recurrence and cancer death. The relative expressions within this morphology of
the prognostically adverse loss of PTEN, and the downstream inactivation of cell
cycle inhibitor p27/Kip1 had been uncertain. In this study, we examined 52 cases
of cribriform cancer by immunohistochemistry for PTEN, p27, and CD44 variant
(v)7/8, and a subset of 17 cases by chromogenic in situ hybridization (ISH) using
probes for PTEN or CDKN1B (gene for p27). The fractions of epithelial pixels
positive by immunohistochemistry and ISH were digitally assessed for benign
acini, high-grade prostatic intraepithelial neoplasia, and 8 morphologic patterns
of cancer. Immunostaining results demonstrated that (1) PTEN loss was significant
for fused small acini, cribriform-central cells, small cribriform acini, and
Gleason grade 5 cells in comparison with other acini; (2) p27 loss was
significant only for cribriform-peripheral cells and borderline significant for
fused small acini in comparison with benign acini; and (3) CD44v7/8 showed
expression loss in cribriform-peripheral cells; other comparisons were not
significant. ISH showed that cribriform cancer had significant PTEN loss
normalized to benign acini (P<.02), whereas Gleason 3 cancer or fused small acini
did not. With CDKN1B, the degree of signal loss among various cancer morphologies
was insignificant. In conclusion, molecular disparities emerged between the fused
small acini and cribriform patterns of Gleason 4 cancer. PTEN or p27 loss as
prognostic factors demands distinct assessment in the varieties of Gleason 4
cancer, and in the biphenotypic peripheral versus central populations in
cribriform structures.
PMID- 28504209
TI - An online readability analysis of pathology-related patient education articles:
an opportunity for pathologists to educate patients.
AB - Information for patients regarding their clinical conditions and treatment
options is widely available online. The American Medical Association and National
Institutes of Health recommend that online patient-oriented materials be written
at no higher than a seventh-grade reading level to ensure full comprehension by
the average American. This study sought to determine whether online patient
oriented materials explaining common pathology procedures are written at
appropriate reading levels. Ten pathology procedures that patients would likely
research were queried into Google search, and plain text from the first 10 Web
sites containing patient education materials for each procedure was analyzed
using 10 validated readability scales. We determined mean reading levels of
materials grouped by readability scale, procedure, and Web site domain, the
overall average reading level of all resources, and popular Web site domains. One
hundred Web sites were accessed; one was omitted for short length (<100 words).
The average reading grade level of the 99 materials, none of which met national
health literacy guidelines (range, 7.3-17.4), was 10.9. Twenty-nine articles
(29%) required a high school education for full comprehension, and 4 (4%)
required an undergraduate college education. Most frequently accessed Web site
domains included medlineplus.gov, webmd.com (both accessed 7 times), and
labtestsonline.org (accessed 6 times). Average reading levels of the 11 most
commonly accessed Web sites ranged from 8.25 (patient.info) to 12.25
(mayoclinic.org). Readability levels of most online pathology-related patient
education materials exceeded those recommended by national health literacy
guidelines. These patient education materials should be revised to help patients
fully understand them.
PMID- 28504210
TI - Arachidonic acid is important for efficient use of light by the microalga
Lobosphaera incisa under chilling stress.
AB - The oleaginous microalga Lobosphaera incisa (Trebouxiophyceae, Chlorophyta)
contains arachidonic acid (ARA, 20:4 n-6) in all membrane glycerolipids and in
the storage lipid triacylglycerol. The optimal growth temperature of the wild
type (WT) strain is 25 degrees C; chilling temperatures (<=15 degrees C) slow its
growth. This effect is more pronounced in the delta-5-desaturase ARA-deficient
mutant P127, in which ARA is replaced with dihomo-gamma-linolenic acid (DGLA,
20:3 n-6). In nutrient-replete cells grown at 25 degrees C, the major chloroplast
lipid monogalactosylglycerol (MGDG) was dominated by C18/C16 species in both
strains. Yet ARA constituted over 10% of the total fatty acids in the WT MGDG as
a component of C20/C18 and C20/C20 species, whereas DGLA was only a minor
component of MGDG in P127. Both strains increased the percentage of 18:3 n-3 in
membrane lipids under chilling temperatures. The temperature downshift led to a
dramatic increase in triacylglycerol at the expense of chloroplast lipids. WT and
P127 showed a similarly high photochemical quantum yield of photosystem II,
whereas non-photochemical quenching (NPQ) and violaxanthin de-epoxidation were
drastically higher in P127, especially at 15 degrees C. Fluorescence anisotropy
measurements indicated that ARA-containing MGDG might contribute to sustaining
chloroplast membrane fluidity upon dropping to the chilling temperature. We
hypothesize that conformational changes in chloroplast membranes and increased
rigidity of the ARA-deficient MGDG of P127 at chilling temperatures are not
compensated by trienoic fatty acids. This might 'lock' violaxanthin de-epoxidase
in the activated state causing high constitutive NPQ and alleviate the risk of
photodamage under chilling conditions in the mutant.
PMID- 28504211
TI - Ectopic adenine nucleotide translocase activity controls extracellular ADP levels
and regulates the F1-ATPase-mediated HDL endocytosis pathway on hepatocytes.
AB - Ecto-F1-ATPase is a complex related to mitochondrial ATP synthase which has been
identified as a plasma membrane receptor for apolipoprotein A-I (apoA-I), the
major protein of high-density lipoprotein (HDL), and has been shown to contribute
to HDL endocytosis in several cell types. On hepatocytes, apoA-I binding to ecto
F1-ATPase stimulates extracellular ATP hydrolysis into ADP, which subsequently
activates a P2Y13-mediated HDL endocytosis pathway. Interestingly, other
mitochondrial proteins have been found to be expressed at the plasma membrane of
several cell types. Among these, adenine nucleotide translocase (ANT) is an
ADP/ATP carrier but its role in controlling extracellular ADP levels and F1
ATPase-mediated HDL endocytosis has never been investigated. Here we confirmed
the presence of ANT at the plasma membrane of human hepatocytes. We then showed
that ecto-ANT activity increases or reduces extracellular ADP level, depending on
the extracellular ADP/ATP ratio. Interestingly, ecto-ANT co-localized with ecto
F1-ATPase at the hepatocyte plasma membrane and pharmacological inhibition of
ecto-ANT activity increased extracellular ADP level when ecto-F1-ATPase was
activated by apoA-I. This increase in the bioavailability of extracellular ADP
accordingly translated into an increase of HDL endocytosis on human hepatocytes.
This study thus uncovered a new location and function of ANT for which activity
at the cell surface of hepatocytes modulates the concentration of extracellular
ADP and regulates HDL endocytosis.
PMID- 28504213
TI - What is it to become an octogenarian 40 years after the first angioplasty?
PMID- 28504214
TI - His master's art, Andreas Gruntzig's approach to performing and teaching coronary
angioplasty.
PMID- 28504215
TI - Commemorating the 15-year anniversary of TAVI: insights into the early stages of
development, from concept to human application, and perspectives.
PMID- 28504212
TI - Psychological Adjustment of Parents of Children Born with Atypical Genitalia 1
Year after Genitoplasty.
AB - PURPOSE: We examined the psychological adjustment of parents of children born
with moderate to severe genital atypia 12 months after their child underwent
genitoplasty. MATERIALS AND METHODS: Parents were recruited longitudinally from a
multicenter collaboration of 10 pediatric hospitals with specialty care for
children with disorders/differences of sex development and/or congenital adrenal
hyperplasia. Parents completed measures of depressive and anxious symptoms,
illness uncertainty, quality of life, posttraumatic stress and decisional regret.
RESULTS: Compared to levels of distress at baseline (before genitoplasty) and 6
months after genitoplasty, data from 25 mothers and 20 fathers indicated
significant improvements in all psychological distress variables. However, a
subset of parents continued endorsing clinically relevant distress. Some level of
decisional regret was endorsed by 28% of parents, although the specific decision
that caused regret was not specified. CONCLUSIONS: Overall the majority of
parents were coping well 1 year after their child underwent genitoplasty. Level
of decisional regret was related to having a bachelor's level of education,
increased levels of illness uncertainty preoperatively and persistent illness
uncertainty at 12 months after genitoplasty but was unrelated to postoperative
complications.
PMID- 28504216
TI - Interventional cardiology's golden age of publishing.
PMID- 28504219
TI - One-year clinical results of the Italian diffuse/multivessel disease ABSORB
prospective registry (IT-DISAPPEARS).
AB - AIMS: The present multicentre prospective study, IT-DISAPPEARS, was designed with
the aim of evaluating early and long-term clinical outcomes of the Absorb BVS in
patients with long coronary lesions and/or multivessel coronary artery disease.
The aim of this article is to present the one-year clinical results of this
study. METHODS AND RESULTS: Between November 2014 and January 2016, we enrolled
1,002 patients undergoing BVS implantation (long lesion [>= 24 mm] of a single
vessel in 80.4%, at least two BVS in two or three coronary vessels in 8.6% and
both criteria in 11%). Clinical presentation was an acute coronary syndrome in
59.8% of patients, including ST-elevation myocardial infarction in 21.8%. The
primary endpoint was the device-oriented composite endpoint (DOCE) of cardiac
death, target vessel MI, and ischaemia-driven TLR at one year. We implanted 2,040
BVS according to a pre-specified technique. One-year follow-up was available in
956 patients (95.4%). The rate of DOCE was 9.9% (95 patients). Cardiac death
occurred in five patients (0.5%), while target vessel MI and TLR each occurred in
45 (4.7%) patients. The one-year rates of all-cause death, non-fatal MI, and any
revascularisation were 1.2%, 5.4%, and 10.9%, respectively. The rate of
definite/probable scaffold thrombosis was 0.9%. CONCLUSIONS: This is the first
study specifically investigating the Absorb technology in patients with a high
atherosclerotic burden and multivessel disease. The mandatory adherence to a pre
specified implantation technique led to minimising the risk of device failure
reported by other studies, in particular with respect to the rate of DOCE and
scaffold thrombosis.
PMID- 28504218
TI - First-in-human evaluation of a novel poly-L-lactide based sirolimus-eluting
bioresorbable vascular scaffold for the treatment of de novo native coronary
artery lesions: MeRes-1 trial.
AB - AIMS: The MeRes-1 trial sought to study the safety and effectiveness of a novel
sirolimus-eluting bioresorbable vascular scaffold (MeRes100 BRS) in treating de
novo native coronary artery lesions by clinical evaluation and using multiple
imaging modalities. METHODS AND RESULTS: The MeRes-1 first-in-human trial was a
single-arm, prospective, multicentre study, which enrolled 108 patients with de
novo coronary artery lesions (116 scaffolds were deployed to treat 116 lesions in
108 patients). At six months, quantitative coronary angiography revealed in
scaffold late lumen loss of 0.15+/-0.23 mm with 0% binary restenosis. Optical
coherence tomography demonstrated minimum scaffold area (6.86+/-1.73 mm2) and
percentage neointimal strut coverage (99.30%). Quantitative intravascular
ultrasound analysis confirmed a 0.14+/-0.16 mm2 neointimal hyperplasia area. At
one year, major adverse cardiac events, a composite of cardiac death, any
myocardial infarction and ischaemia-driven target lesion revascularisation,
occurred in only one patient (0.93%) and there was no scaffold thrombosis
reported. At one year, computed tomography angiography demonstrated that all
scaffolds were patent and in-scaffold mean percentage area stenosis was 11.33+/
26.57%. CONCLUSIONS: The MeRes-1 trial demonstrated the safety and effectiveness
of MeRes100 BRS. The favourable clinical outcomes and effective vascular
responses have provided the basis for further studies in a larger patient
population. The MeRes-1 trial is registered at the Clinical Trials Registry
India.
PMID- 28504220
TI - EAPCI registries: a first step towards systematic monitoring of European
interventional cardiology practice.
PMID- 28504221
TI - Current trends in coronary interventions: an overview from the EAPCI registries.
PMID- 28504222
TI - Current trends in structural heart interventions: an overview of the EAPCI
registries.
PMID- 28504223
TI - Belgium: coronary and structural heart interventions from 2010 to 2015.
AB - In a ranking of the gross domestic product per capita in 2015, Belgium ranked
19th in the world according to the International Monetary Fun1d and the World
Bank. It has a Human Development Index of 0.890, in which it is preceded by only
20 other countries in the world. This is, at least in part, due to a well
developed social security system on which all citizens can rely. Over the last 5
10 years, however, this system has come under increasing pressure. This has
resulted in insufficient, incomplete and late reimbursement of all technologies
that were introduced over the last ten years in the cathlab: intracoronary
imaging techniques are not reimbursed at all, and FFR only to a vastly
insufficient degree. For several structural heart interventions, a system of
limited and incomplete reimbursement has recently been set up, with a requirement
to organise these procedures within the frames of hospital networks. Numbers of
PCIs have risen by 15% over the last four years, coinciding with an increase in
the number of cathlabs by 50%, aiming at better access to primary PCI for STEMI
patients. This has also resulted in a decrease in the average procedure volume
per centre. Two thirds of PCIs are performed via the radial access. DES
penetration has increased to 74%, approaching 100% in some centres, while the
uptake of BRS has been very limited so far.
PMID- 28504224
TI - Denmark: coronary and structural heart interventions from 2010 to 2015.
AB - Interventional cardiology in Denmark has been carried out since the mid 1980s.
Interventional cardiology is only performed at a few high-volume centres.
Healthcare coverage is universal and is essentially free of charge. Hospitals are
mostly publicly owned and financed by fixed budgets and, in part, an activity
based funding system. Approximately 30,000 coronary angiographies (CAG), 10,000
percutaneous coronary interventions (PCIs) of which approximately 25% are primary
PCIs, and 500 transcatheter aortic valve implantations (TAVIs) are carried out
each year. The numbers of CAG and PCI have reached a plateau in recent years,
whereas structural heart interventions, in particular TAVI, are increasing.
Around 90% of all patients treated with PCI have a stent implanted, with more
than 95% of these being drug-eluting stents. There is a low but increasing use of
bioabsorbable scaffolds and drug-eluting balloons.
PMID- 28504225
TI - Egypt: coronary and structural heart interventions from 2010 to 2015.
AB - Interventional cardiology procedures are constantly increasing in numbers and in
quality, especially in developing countries such as Egypt. The numbers and types
of procedure now available have driven development in the field and in its
accompanying services. The aim of this short report is to present a review of the
development of interventional cardiology in Egypt during the period 2010-2015 and
the demographic, economic and educational factors that have affected this
process. We collected and analysed data provided by different centres and from
the distributors of intervention tools for the years 2010 to 2015. Analysis of
these data showed a steady growth of primary PCI, amounting to a threefold
increase over the six-year period. There are increasing numbers of PCI-capable
centres, especially in Cairo. Almost 55,000 PCIs are performed yearly in Egypt
utilising around 100,000 stents; the percentage of drug-eluting stents (DES) used
has increased to 65-70% (90% in private and insured patients). Structural
intervention is growing fast for congenital heart disease, and balloon mitral
valvuloplasty has become the default strategy. The numbers of TAVI and EVAR are
also increasing, although cost remains the greatest challenge. These changes can
be attributed to the increasing numbers of ischaemic heart disease patients over
the last 25 years, involving improved education and awareness, patients
presenting at a younger age, and improved practice in intervention. In Egypt,
there has been a steady growth in PCI and intervention tools which has been
faster in coronary and congenital heart disease than in structural heart disease
during the period from 2010 to 2015.
PMID- 28504226
TI - France: coronary and structural heart interventions from 2010 to 2015.
AB - France, with its 66 million inhabitants, has a long tradition in interventional
cardiology, with numerous innovations and contributions to the dynamism of
European activity. The development of interventional cardiology requires
supervised training, organisation and participation in studies. This also
translates into an ever-expanding clinical activity since 2010, such as the
coronary and structural interventions that are detailed in the present review.
PMID- 28504227
TI - Israel: coronary and structural heart interventions from 2010 to 2015.
AB - The Israel Heart Society is a member of the European Society of Cardiology, and
the Israeli Working Group of Interventional Cardiology is an active participant
in EAPCI. The aim of this manuscript is to provide a snapshot of cardiac
interventions performed in the State of Israel during the period 2010-2015. Data
for this manuscript were collected via collaboration with the National Diseases
Registries Unit of the Israel Center for Disease Control. During the survey
period, the Israeli population increased by 7% but only one additional hospital
with an active cardiac catheterisation laboratory was opened. The vast majority
of the percutaneous procedures are performed in public hospital settings. Total
coronary angiography procedures remained stable throughout the survey period, and
the percentage of PCI out of total coronary angiography procedures remained
approximately 50% throughout the survey period. More than 90% of the PCI
procedures were performed using stent deployment, and the use of drug-eluting
stents increased significantly during the survey period from 46% in 2010 to 92%
in 2015. The number of TAVI procedures increased dramatically, by more than
sixfold, from 130 procedures in 2010 to 851 procedures in 2015 (with 130
implants/million population at Q4 of 2015). The vast majority of interventional
cardiology procedures are funded by the governmental healthcare providers, and
all the citizens of the country have access to the most advanced cardiac
interventions. If corrected for the increase in the population, the volumes of
coronary interventions are decreasing throughout the country. However, structural
heart disease interventions, and specifically valvular interventions, are growing
rapidly and this trend is expected to continue in the near future.
PMID- 28504228
TI - Italy: coronary and structural heart interventions from 2010 to 2015.
AB - The aim of this report is to analyse trends in Italian cathlab activity between
2010 and 2015. Data were obtained from the national database of the Italian
Society of Interventional Cardiology (GISE), which includes 97% of Italian
cardiac catheterisation laboratories. The number of percutaneous coronary
interventions (PCI) has remained relatively stable in the past five years. We
have observed a significant increase in the number of primary PCI (pPCI) from
471.5 to 557.5 per million inhabitants with a consequent reduction of rescue
primary PCI/fibrinolysis. One of the possible explanations for this might be the
extensive networking for primary PCI and the adoption of Stent for Life
initiatives in five regions. There has been a notably increased use of drug
eluting stents and, despite the fact that the introduction of bioabsorbable
vascular scaffolds is recent, there is a slight, progressively positive trend.
Invasive physiologic evaluation of coronary stenosis has markedly increased.
Radial artery access has become the default option for PCI and for pPCI. In the
last five years, TAVI procedures have doubled in number, while MitraClip and
mitral repair procedures have shown a fivefold increase. Left atrial appendage
(LAA) occlusion procedures have more than doubled in four years.
PMID- 28504229
TI - Kazakhstan: coronary and structural heart interventions from 2010 to 2015.
AB - This paper presents data on the nascence and development of the interventional
cardiology service in Kazakhstan. It provides details of the structure of the
Kazakhstan interventional cardiology service, staff training, the number of
coronary and structural heart interventions for the period of 2010-2015, as well
as the peculiarities of the capitation payment method. The number of coronary
interventions is increasing year by year, though the number of intracoronary
imaging techniques and intracoronary flow/pressure techniques remains inadequate.
Structural heart interventions are mostly performed at tertiary hospital level,
with an ever increasing number of transcatheter aortic valve implantation (TAVI)
procedures.
PMID- 28504230
TI - Macedonia: coronary and structural heart interventions from 2010 to 2015.
AB - The aim of this report is to describe invasive cardiology procedural practice in
Macedonia during the period from 2010 to 2015. Details of all consecutive 39,899
patients who underwent cardiovascular, peripheral or structural heart procedures
during the period from 2010 until 2015 were examined. Clinical and procedure
characteristics, access site, procedural success and complications were analysed.
The number of coronary angiographies increased from 5,540 in 2010 to 8,550 in
2015. Transfemoral access (TFA) was present in 4% of coronary angiographies in
2010 and had decreased to 1% in 2015. The number of primary percutaneous coronary
interventions (PCI) for acute ST-segment elevation myocardial infarction
increased from 763 to 1,175 and both chronic total occlusion and left main
coronary artery interventions also increased over time. In 2015, the drug-eluting
stent penetration rate was 65%. Structural heart interventions, including
transcatheter aortic valve implantations (TAVI) were introduced in 2014 and 23
TAVI cases have since been performed. Transradial access was performed in 38,455
(96%) of all patients. Wrist access adoption in the majority of cardiovascular
interventions is possible in all PCI centres in Europe if an appropriate national
strategy is developed.
PMID- 28504231
TI - Poland: coronary and structural heart interventions from 2010 to 2015.
AB - For the last five years, invasive cardiology in Poland has developed extensively.
Currently, 98% of the 161 Polish cathlabs operate in 24/7 mode, 37 of them
supported by cardiac surgery departments on-site. A certification curriculum for
interventional cardiology operators is supported by dedicated workshops and
scientific meetings during national conferences. The rise in the number of
coronary angiographies and PCIs was paralleled by an increased use of drug
eluting stents, bioresorbable vascular scaffolds and physiologic assessment of
coronary arteries. Radial artery access has become the default option for PCI. A
rapid adoption of the EAPCI Stent for Life Initiative resulted in a significant
increase in primary PCIs. Unlike coronary interventions, structural heart
interventions have evolved unevenly, despite the solid network of Heart Teams set
up in the 21 most experienced centres. Left atrial appendage closure is offered
in an increasing number of cathlabs. MitraClip therapy remains largely underused
(1 procedure/million population/year). Despite the slow growth of TAVI since
2008, the current annual number of 17.1 TAVI procedures per million population is
incomparable with countries in Western Europe. A recently introduced EAPCI Valve
for Life campaign was followed by a 42.6% annual increase in TAVI procedures and
an improvement in patients' access to therapy in life-saving indications.
PMID- 28504232
TI - Portugal: coronary and structural heart interventions from 2010 to 2015.
AB - The aim of the present paper is to report trends in Portuguese interventional
cardiology from 2010 to 2015. We studied data from the prospective multicentre
Portuguese National Registry of Interventional Cardiology (RNCI) to analyse
percutaneous coronary intervention (PCI) procedures and structural heart
interventions from 2010 to 2015. A total of 73,977 PCIs and 780 transcatheter
aortic valve implants were performed during the study period. Since 2010 there
has been a 60% increase in PCI procedures and a twofold increase in primary
angioplasty rates reaching 316 per million population. Significant PCI trends
were observed, notably the increase of radial access, a reduction in restenosis
indications, as well as an increase in stent use, including DES, in imaging and
in functional techniques. Importantly, there was a fourfold increase in the TAVI
rates reaching 29 per million population.
PMID- 28504233
TI - Serbia: coronary and structural heart interventions from 2010 to 2015.
AB - Serbia's interventional community has been facing the multifaceted challenge of
an ageing population with cardiovascular diseases as the primary cause of death
nationwide, coronary artery disease (CAD) being the most prevalent subset. The
following two fields of activity have marked the trajectory of progress in the
field of interventional cardiology in Serbia: first, the expansion of the
infrastructure, mainly through the opening of new catheterisation laboratories
across all of the country's administrative regions, which has resulted in better
accessibility to coronary interventions for the general population; second, the
creation of national platforms for continuous education, training and the
promotion of clinical research in interventional cardiology, with close
programmatic links to European Association of Percutaneous Cardiovascular
Interventions (EAPCI)-based educational initiatives, including the curriculum for
interventional cardiology. As growth seems to be inherent to the concept of
progress, we report here on the expanding numbers of coronary interventions in
the period between January 2010 and December 2015, and the early experiences with
structural heart interventions in Serbia.
PMID- 28504234
TI - Spain: coronary and structural heart interventions from 2010 to 2015.
AB - Since 1990 The Spanish Society of Cardiology Working Group on Cardiac
Catheterization and Interventional Cardiology has presented a yearly report on
the data collected in the National Registry, with online support since 2010. The
Steering Committee has analysed all data provided voluntarily by institutions,
which consisted of a total of anywhere between 105 and 113 hospitals. Medical
care was provided to a population of 46.8 million inhabitants in 2015. During
this period, diagnostic procedures increased progressively from 2010, reaching a
maximum of 145,836 in 2015, 86% (125,484) corresponding to coronary angiograms.
This means a ratio of 3,127 diagnostic studies per million inhabitants and 2,746
coronary angiograms per million inhabitants. Total percutaneous coronary
interventions have increased to 67,671 procedures, with a ratio of 1,466 per
million inhabitants where 18,418 were carried out during the acute phase of
myocardial infarction (21.7%). Radial access has been successfully implemented in
up to 73.8% of diagnostic procedures and 76.1% of percutaneous interventions.
Concerning structural interventions such as septal defects, valve interventions
and closure of left atrial appendage, these have had a marked evolution over
time, with a total of 1,586 TAVI and 334 LAA closure procedures performed in
2015.
PMID- 28504235
TI - Sweden: coronary and structural heart interventions from 2010 to 2015.
AB - Sparsely populated and with wide non-urbanised areas, Sweden faces specific
challenges in providing publicly financed, high-quality and equal healthcare to
all parts of the country. As a result, a decentralised organisation for acute
coronary care has been developed with coronary care units and catheterisation
laboratories in several small- and medium-sized city areas. In contrast, highly
specialised non-emergent interventional procedures are centralised to a few high
volume centres, mainly located at university hospitals in large city areas.
Nationwide quality registries with nearly complete coverage facilitate healthcare
quality improvement and form a basis for clinical research. In this report, we
present an overview of demographics, healthcare organisation, quality registries
and procedural data for coronary and structural heart interventions in Sweden
over the past six years.
PMID- 28504236
TI - Switzerland: coronary and structural heart interventions from 2010 to 2015.
AB - In 2015, Switzerland had a population of 8.3 million inhabitants. Since the first
coronary angioplasty performed by Andreas Gruntzig in Zurich in 1977, the number
of percutaneous procedures has steadily increased. The aim of this report is to
summarise the current state of catheter-based cardiac interventions in adults in
the country and to detail trends between 2010 and 2015. Since 1987, the Working
Group for Interventional Cardiology of the Swiss Society of Cardiology has
collected annually aggregate data from all facilities with cardiac
catheterisation laboratories in the country. In 2015, a total of 37 institutions
covered 17 of the 26 Swiss cantons. Over the six-year period, there was a
continuous increase in the number of coronary angiography and percutaneous
coronary interventions (PCI) (median increase rate of 3.2%/year for coronary
angiography and of 2.6%/year for PCI). Notable was the adoption of the
transradial approach for PCI, going from a median rate of 17% in 2012 to 51.9% in
2015. With respect to structural heart interventions, the number of patent
foramen ovale as well as atrial septal defect closures has remained stable, while
the number of transcatheter aortic valve implantations and transcatheter mitral
valve repairs has shown a fourfold increase.
PMID- 28504237
TI - Turkey: coronary and structural heart interventions from 2010 to 2015.
AB - Growing populations and ageing demographics lead to an increased burden of
ischaemic heart disease and related cardiovascular interventions, resulting in
pressure on healthcare systems. Although the healthcare system in Turkey has
undergone comprehensive remodelling over the last decade, there are many
challenges to overcome, including better reimbursement for cardiovascular
interventions, standardisation of interventional cardiology services and research
related activities. In this manuscript, we present an overview of coronary and
structural heart interventions in Turkey, as well as providing information on
current reimbursement policies and the healthcare system.
PMID- 28504238
TI - United Kingdom: coronary and structural heart interventions from 2010 to 2015.
AB - In the United Kingdom, a clinical data set is completed for every patient
undergoing coronary intervention and certain structural interventions, and sent
to central servers in the National Institute for Cardiovascular Outcomes Research
(NICOR) on behalf of the British Cardiovascular Intervention Society (BCIS).
These data are linked to the national mortality register. In addition, data are
obtained about the structure of healthcare provision using an annual survey.
Analyses of these data are provided for different audiences in several formats.
Public reports of individual consultant operator activity and risk-adjusted
outcomes from percutaneous coronary intervention (PCI) have also been produced
annually since 2012. Transcatheter aortic valve implantation (TAVI) has been
performed since 2007. Over 2,000 cases were performed in 2015, giving a rate of
30 per million population. Complications to discharge have fallen as case mix has
changed and technologies improved. While the mean age has remained about 81
years, the logistic EuroSCORE of patients treated by TAVI has fallen from about
22 in 2010 to 18 in 2015. Tracked 30-day mortality was 3.7% in 2014. Left atrial
appendage occlusion and patent foramen ovale (PFO) closure for stroke, and the
use of the MitraClip(r) system (Abbott Vascular, Santa Clara, CA, USA) for mitral
regurgitation have been funded through a process called "commissioning through
evaluation".
PMID- 28504240
TI - MALDI-TOF MS in the Microbiology Laboratory: Current Trends.
AB - Within less than a decade matrix-assisted laser desorption/ionization time-of
flight mass spectrometry (MALDI-TOF MS) has become a gold standard for microbial
identification in clinical microbiology laboratories. Besides identification of
microorganisms the typing of single strains as well as the antibiotic and
antimycotic resistance testing has come into focus in order to speed up the
microbiological diagnostic. However, the full potential of MALDI-TOF MS has not
been tapped yet and future technological advancements will certainly expedite
this method towards novel applications and enhancement of current practice. So,
the following chapter shall be rather a brainstorming and forecast of how MALDI
TOF MS will develop to influence clinical diagnostics and microbial research in
the future. It shall open up the stage for further discussions and does not claim
for overall validity.
PMID- 28504239
TI - Sustained safety and clinical performance of a drug-eluting absorbable metal
scaffold up to 24 months: pooled outcomes of BIOSOLVE-II and BIOSOLVE-III.
AB - AIMS: We aimed to assess the safety and performance of the DREAMS 2G scaffold up
to 24 months post implant. METHODS AND RESULTS: The present study population
comprises a total of 184 patients with 189 lesions who were enrolled in the
prospective, multicentre BIOSOLVE-II and BIOSOLVE-III trials. Clinical follow-up
was scheduled at one, six, 12, 24 and 36 months. The present report includes
pooled follow-up data at six months and BIOSOLVE-II data at 24 months. Patients
were 65.5+/-10.8 years old, and lesions were 12.5+/-5.1 mm long with reference
diameters of 2.7+/-0.4 mm. Procedural success was obtained in 97.8%. At six
months, the composite clinical endpoint target lesion failure was 3.3% (95% CI:
1.2-7.1), based on two cardiac deaths (1.1%, one unknown and one not device
related), one target vessel myocardial infarction (0.6%), and three clinically
driven target lesion revascularisations (1.7%). For BIOSOLVE-II at 24 months, the
target lesion failure rate was 5.9% (95% CI: 2.4-11.8), based on two cardiac
deaths (1.7%), one target vessel myocardial infarction (0.9%) and four target
lesion revascularisations (3.4%). There was no definite or probable scaffold
thrombosis. CONCLUSIONS: The present analysis provides additional evidence on the
safety of a drug-eluting absorbable metal scaffold with promising clinical
outcomes up to 24 months and absence of definite or probable scaffold thrombosis.
PMID- 28504241
TI - Antiviral drug resistance and hepatitis B: a continuing public health problem.
AB - The use of selective antiviral therapy has been very successful in controlling
HBV replication in individuals, leading to a reduction in disease progression and
mortality. However, the use of first-generation therapies, often the only
available option in low-resource settings, can result in a high prevalence of
drug resistance mutations. Variants selected by antiviral therapies targeting the
viral polymerase can also result in variants in the viral envelope. These
variants can allow the virus to escape the host immune response. The effect of
antiviral selection pressure on viral variants that may contribute to immune
escape requires further investigation.
PMID- 28504242
TI - Simultaneous microfluidic spinning of multiple strands of submicron fiber for the
production of free-standing porous membranes for biological application.
AB - Microfibers produced using electrospinning and microfluidics-based technologies
have been developed as a powerful tool in tissue engineering applications such as
drug delivery and scaffolds. The applications of these fibers, however, have been
limited because of the hazardous solvents used to make them, difficulties in
controlling the pore sizes of their membrane forms, and downscaling the size of
the fiber. Nevertheless, extending the use of these fibers, for example in the
production of a free-standing porous membrane appropriate for cell-based
research, is highly needed for tissue engineering, organ-on-a-chip, and drug
delivery research and applications. Here, we fabricated a free-standing porous
membrane by using a novel method that involved simultaneously spinning multiple
strands of submicron-thick 'noodle-like' fibers. In addition to the novelty of
the single noodle fiber in overcoming the size-reducing limitations of
conventional microfluidic spinning methods, these fibers can hence form the units
of 'noodle membranes' whose pores have sizes that the convention electrospinning
method cannot achieve. We confirmed the potential of the noodle membrane to serve
as a free-standing porous membrane in two simple experiments. Also, we found that
noodle membranes have an advantage in loading different amounts of different
materials in itself that it was also shown to be of use as a new type of scaffold
for complex tissue regeneration. Therefore, the proposed noodle membrane can be
an effective tool in tissue engineering applications and biological studies.
PMID- 28504243
TI - Cancers of the appendix. Case report and literatures review.
AB - : Cancers of appendix are very uncommon. As reported in the case of 85 years old
man, that underwent right emicolectomy with restoration of bowel continuity, the
appendix was found to be gangrenous and perforated during the surgery. The
hystology that comes out was adenocarcinoma of appendix that after 1 yars of
follow up ramanins asymptomatic. At last the emicolectomy rappresent the best
surgical treatment for all appendix neoplasm, that could be recognised from the
surgeon when possible wiht intraoperavite histological examination. KEY WORDS:
Appendix, Cancer, Incidental diagnosis, Right emicolectomy.
PMID- 28504244
TI - Mid-infrared coincidence measurements on twin photons at room temperature.
AB - Quantum measurements using single-photon detectors are opening interesting new
perspectives in diverse fields such as remote sensing, quantum cryptography and
quantum computing. A particularly demanding class of applications relies on the
simultaneous detection of correlated single photons. In the visible and near
infrared wavelength ranges suitable single-photon detectors do exist. However,
low detector quantum efficiency or excessive noise has hampered their mid
infrared (MIR) counterpart. Fast and highly efficient single-photon detectors are
thus highly sought after for MIR applications. Here we pave the way to quantum
measurements in the MIR by the demonstration of a room temperature coincidence
measurement with non-degenerate twin photons at about 3.1 MUm. The experiment is
based on the spectral translation of MIR radiation into the visible region, by
means of efficient up-converter modules. The up-converted pairs are then detected
with low-noise silicon avalanche photodiodes without the need for cryogenic
cooling.
PMID- 28504246
TI - Diffusive and martensitic nucleation kinetics in solid-solid transitions of
colloidal crystals.
AB - Solid-solid transitions between crystals follow diffusive nucleation, or various
diffusionless transitions, but these kinetics are difficult to predict and
observe. Here we observed the rich kinetics of transitions from square lattices
to triangular lattices in tunable colloidal thin films with single-particle
dynamics by video microscopy. Applying a small pressure gradient in defect-free
regions or near dislocations markedly transform the diffusive nucleation with an
intermediate-stage liquid into a martensitic generation and oscillation of
dislocation pairs followed by a diffusive nucleus growth. This transformation is
neither purely diffusive nor purely martensitic as conventionally assumed but a
combination thereof, and thus presents new challenges to both theory and the
empirical criterion of martensitic transformations. We studied how pressure,
density, grain boundary, triple junction and interface coherency affect the
nucleus growth, shape and kinetic pathways. These novel microscopic kinetics cast
new light on control solid-solid transitions and microstructural evolutions in
polycrystals.
PMID- 28504245
TI - Macrophage-derived IL-1alpha promotes sterile inflammation in a mouse model of
acetaminophen hepatotoxicity.
AB - The metabolic intermediate of acetaminophen (APAP) can cause severe hepatocyte
necrosis, which triggers aberrant immune activation of liver non-parenchymal
cells (NPC). Overzealous hepatic inflammation determines the morbidity and
mortality of APAP-induced liver injury (AILI). Interleukin-1 receptor (IL-1R)
signaling has been shown to play a critical role in various inflammatory
conditions, but its precise role and underlying mechanism in AILI remain
debatable. Herein, we show that NLRP3 inflammasome activation of IL-1beta is
dispensable to AILI, whereas IL-1alpha, the other ligand of IL-1R1, accounts for
hepatic injury by a lethal dose of APAP. Furthermore, Kupffer cells function as a
major source of activated IL-1alpha in the liver, which is activated by damaged
hepatocytes through TLR4/MyD88 signaling. Finally, IL-1alpha is able to
chemoattract and activate CD11b+Gr-1+ myeloid cells, mostly neutrophils and
inflammatory monocytes, to amplify deteriorated inflammation in the lesion.
Therefore, this work identifies that MyD88-dependent activation of IL-1alpha in
Kupffer cells plays a central role in the immunopathogenesis of AILI and
implicates that IL-1alpha is a promising therapeutic target for AILI treatment.
PMID- 28504248
TI - The flavonoid TL-2-8 induces cell death and immature mitophagy in breast cancer
cells via abrogating the function of the AHA1/Hsp90 complex.
AB - The flavonoid quercetin exhibits significant anticancer activities with few side
effects. In the current study, we characterized TL-2-8, a quercetin derivative,
as a novel anticancer agent in vitro and in vivo. Cell proliferation and
viability were assessed using Cell Counting Kit-8 and CellTiter-Blue assay,
respectively. Cell death was examined using PI staining or a TUNEL assay.
Mitophagy was determined by measuring autophagic flux and by confocal imaging.
Protein expression was examined by Western blotting. We found that TL-2-8
selectively inhibited the proliferation and decreased the viability of various
cancer cells (the anti-proliferation IC50 values in MDA-MB-231, MDA-MB-468 and
MCF-7 breast cancer cells at 72 h were 8.28, 8.56, and 9.58 MUmol/L,
respectively), and it displayed only slight cytotoxicity against normal MCF-10A
and HEK-293 cells. In MDA-MB-231 and MDA-MB-468 breast cancer cells, TL-2-8
treatment induced the degradation of multiple Hsp90 client proteins without
inducing Hsp70. TL-2-8 (3, 6, 12 MUmol/L) dose-dependently inhibited the
expression of AHA1, an activator of Hsp90 ATPase, and decreased Hsp90-AHA1
complex formation, leading to decreased Hsp90 chaperone function and reduced polo
like kinase 1 (PLK1) signaling. Consequently, impaired mitophagy was induced via
the downregulation of lysosomal-associated membrane protein 2 (LAMP2). The in
vivo anticancer effects of TL-2-8 were evaluated in an MDA-MB-231 breast cancer
xenograft model, which was treated with TL-2-8 (25, 50, 100 mg.kg-1.d-1, po).
Administration of TL-2-8 resulted in tumor growth inhibition rates of 37.9%,
58.9% and 70.9%, respectively, whereas quercetin treatment (100 mg.kg-1.d-1, po)
produced only a lower tumor growth inhibition rate (49.5%). Furthermore, TL-2-8
treatment significantly extended the lifespan of mice bearing MDA-MB-231 breast
cancer cell xenografts. Our results demonstrate that TL-2-8 induces significant
cell death and immature mitophagy in breast cancer cells in vitro and in vivo via
AHA1 abrogation.
PMID- 28504247
TI - Actomyosin meshwork mechanosensing enables tissue shape to orient cell force.
AB - Sculpting organism shape requires that cells produce forces with proper
directionality. Thus, it is critical to understand how cells orient the
cytoskeleton to produce forces that deform tissues. During Drosophila
gastrulation, actomyosin contraction in ventral cells generates a long, narrow
epithelial furrow, termed the ventral furrow, in which actomyosin fibres and
tension are directed along the length of the furrow. Using a combination of
genetic and mechanical perturbations that alter tissue shape, we demonstrate that
geometrical and mechanical constraints act as cues to orient the cytoskeleton and
tension during ventral furrow formation. We developed an in silico model of two
dimensional actomyosin meshwork contraction, demonstrating that actomyosin
meshworks exhibit an inherent force orienting mechanism in response to mechanical
constraints. Together, our in vivo and in silico data provide a framework for
understanding how cells orient force generation, establishing a role for
geometrical and mechanical patterning of force production in tissues.
PMID- 28504249
TI - Treating breast cancer metastasis with cabazitaxel-loaded polymeric micelles.
AB - Cancer metastasis is the primary cause of high mortality in breast cancer
patients. In this study, we loaded an anti-cancer drug, cabazitaxel (CTX), into
polymeric micelles (CTX-loaded polymeric micelles, PCMs), and explored their
therapeutic efficacy in breast cancer metastasis. The characteristics of PCMs
were investigated, and their anti-metastatic efficacy was assessed using in vitro
and in vivo evaluations. PCMs had an average diameter of 50.13+/-11.96 nm with a
CTX encapsulation efficiency of 97.02%+/-0.97%. PCMs could be effectively
internalized into metastatic 4T1 breast cancer cells in vitro. CTX (10 ng/mL) or
an equivalent concentration in PCMs did not significantly affected the viability
of 4T1 cells, but dramatically decreased the cell migration activities. In an
orthotopic metastatic breast cancer model, intravenously administered PCMs could
be efficiently delivered to the tumor sites, resulting in a 71.6% inhibition of
tumor growth and a 93.5% reduction of lung metastases. Taken together, our
results verify the anti-metastatic efficacy of PCMs, thus providing an
encouraging strategy for treating breast cancer metastasis.
PMID- 28504250
TI - Curcumin enhances vascular contractility via induction of myocardin in mouse
smooth muscle cells.
AB - A variety of cardiovascular diseases is accompanied by the loss of vascular
contractility. This study sought to investigate the effects of curcumin, a
natural polyphenolic compound present in turmeric, on mouse vascular
contractility and the underlying mechanisms. After mice were administered
curcumin (100 mg.kg-1.d-1, ig) for 6 weeks, the contractile responses of the
thoracic aorta to KCl and phenylephrine were significantly enhanced compared with
the control group. Furthermore, the contractility of vascular smooth muscle (SM)
was significantly enhanced after incubation in curcumin (25 MUmol/L) for 4 days,
which was accompanied by upregulated expression of SM marker contractile proteins
SM22alpha and SM alpha-actin. In cultured vascular smooth muscle cells (VSMCs),
curcumin (10, 25, 50 MUmol/L) significantly increased the expression of
myocardin, a "master regulator" of SM gene expression. Curcumin treatment also
significantly increased the levels of caveolin-1 in VSMCs. We found that as a
result of the upregulation of caveolin-1, curcumin blocked the activation of
notch1 and thereby abolished Notch1-inhibited myocardin expression. Knockdown of
caveolin-1 or activation of Notch1 signaling with Jagged1 (2 MUg/mL) diminished
these effects of curcumin in VSMCs. These findings suggest that curcumin induces
the expression of myocardin in mouse smooth muscle cells via a variety of
mechanisms, including caveolin-1-mediated inhibition of notch1 activation and
Notch1-mediated repression of myocardin expression. This may represent a novel
pathway, through which curcumin protects blood vessels via the beneficial
regulation of SM contractility.
PMID- 28504251
TI - Programmable co-delivery of the immune checkpoint inhibitor NLG919 and
chemotherapeutic doxorubicin via a redox-responsive immunostimulatory polymeric
prodrug carrier.
AB - To achieve synergistic therapeutic efficacy and prevent cancer relapse,
chemotherapy and immunotherapy have been combined as a new modality for tumor
treatment. In this work, we designed a redox-responsive immunostimulatory
polymeric prodrug carrier, PSSN10, for programmable co-delivery of an immune
checkpoint inhibitor NLG919 (NLG) and a chemotherapeutic doxorubicin (DOX). NLG
containing PSSN10 prodrug polymers were self-assembled into nano-sized micelles
that served as a carrier to load DOX (DOX/PSSN10 micelles). DOX/PSSN10 micelles
displayed spherical morphology with a size of ~170 nm. DOX was effectively loaded
into PSSN10 micelles with a loading efficiency of 84.0%. In vitro DOX release
studies showed that rapid drug release could be achieved in the highly redox
environment after intracellular uptake by tumor cells. In 4T1.2 tumor-bearing
mice, DOX/PSSN10 micelles exhibited greater accumulation of DOX and NLG in the
tumor tissues compared with other organs. The PSSN10 carrier dose-dependently
enhanced T-cell immune responses in the lymphocyte-Panc02 co-culture experiments,
and significantly inhibited tumor growth in vivo. DOX/PSSN10 micelles showed
potent cytotoxicity in vitro against 4T1.2 mouse breast cancer cells and PC-3
human prostate cancer cells comparable to that of DOX. In 4T1.2 tumor-bearing
mice, DOX/PSSN10 mixed micelles (5 mg DOX/kg, iv) was more effective than DOXIL
(a clinical formulation of liposomal DOX) or free DOX in inhibiting the tumor
growth and prolonging the survival of the treated mice. In addition, a more
immunoactive tumor microenvironment was observed in the mice treated with PSSN10
or DOX/PSSN10 micelles compared with the other treatment groups. In conclusion,
systemic delivery of DOX via PSSN10 nanocarrier results in synergistic anti-tumor
activity.
PMID- 28504253
TI - Dynamic diversity of synthetic supramolecular polymers in water as revealed by
hydrogen/deuterium exchange.
AB - Numerous self-assembling molecules have been synthesized aiming at mimicking both
the structural and dynamic properties found in living systems. Here we show the
application of hydrogen/deuterium exchange (HDX) mass spectrometry (MS) to
unravel the nanoscale organization and the structural dynamics of synthetic
supramolecular polymers in water. We select benzene-1,3,5-tricarboxamide (BTA)
derivatives that self-assemble in H2O to illustrate the strength of this
technique for supramolecular polymers. The BTA structure has six exchangeable
hydrogen atoms and we follow their exchange as a function of time after diluting
the H2O solution with a 100-fold excess of D2O. The kinetic H/D exchange profiles
reveal that these supramolecular polymers in water are dynamically diverse; a
notion that has previously not been observed using other techniques. In addition,
we report that small changes in the molecular structure can be used to control
the dynamics of synthetic supramolecular polymers in water.
PMID- 28504255
TI - Energy efficiency to reduce residential electricity and natural gas use under
climate change.
AB - Climate change could significantly affect consumer demand for energy in
buildings, as changing temperatures may alter heating and cooling loads. Warming
climates could also lead to the increased adoption and use of cooling
technologies in buildings. We assess residential electricity and natural gas
demand in Los Angeles, California under multiple climate change projections and
investigate the potential for energy efficiency to offset increased demand. We
calibrate residential energy use against metered data, accounting for differences
in building materials and appliances. Under temperature increases, we find that
without policy intervention, residential electricity demand could increase by as
much as 41-87% between 2020 and 2060. However, aggressive policies aimed at
upgrading heating/cooling systems and appliances could result in electricity use
increases as low as 28%, potentially avoiding the installation of new generation
capacity. We therefore recommend aggressive energy efficiency, in combination
with low-carbon generation sources, to offset projected increases in residential
energy demand.
PMID- 28504254
TI - Neural circuits for long-term water-reward memory processing in thirsty
Drosophila.
AB - The intake of water is important for the survival of all animals and drinking
water can be used as a reward in thirsty animals. Here we found that thirsty
Drosophila melanogaster can associate drinking water with an odour to form a
protein-synthesis-dependent water-reward long-term memory (LTM). Furthermore, we
found that the reinforcement of LTM requires water-responsive dopaminergic
neurons projecting to the restricted region of mushroom body (MB) beta' lobe,
which are different from the neurons required for the reinforcement of learning
and short-term memory (STM). Synaptic output from alpha'beta' neurons is required
for consolidation, whereas the output from gamma and alphabeta neurons is
required for the retrieval of LTM. Finally, two types of MB efferent neurons
retrieve LTM from gamma and alphabeta neurons by releasing glutamate and
acetylcholine, respectively. Our results therefore cast light on the cellular and
molecular mechanisms responsible for processing water-reward LTM in Drosophila.
PMID- 28504256
TI - Explosive eruption, flank collapse and megatsunami at Tenerife ca. 170 ka.
AB - Giant mass failures of oceanic shield volcanoes that generate tsunamis
potentially represent a high-magnitude but low-frequency hazard, and it is
actually difficult to infer the mechanisms and dynamics controlling them. Here we
document tsunami deposits at high elevation (up to 132 m) on the north-western
slopes of Tenerife, Canary Islands, as a new evidence of megatsunami generated by
volcano flank failure. Analyses of the tsunami deposits demonstrate that two main
tsunamis impacted the coasts of Tenerife 170 kyr ago. The first tsunami was
generated during the submarine stage of a retrogressive failure of the northern
flank of the island, whereas the second one followed the debris avalanche of the
subaerial edifice and incorporated pumices from an on-going ignimbrite-forming
eruption. Coupling between a massive retrogressive flank failure and a large
explosive eruption represents a new type of volcano-tectonic event on oceanic
shield volcanoes and a new hazard scenario.
PMID- 28504258
TI - Neuroimmunology: Macrophages help you burn energy.
PMID- 28504252
TI - Pulmonary delivery of nanoparticle chemotherapy for the treatment of lung
cancers: challenges and opportunities.
AB - Lung cancer is the second most prevalent and the deadliest among all cancer
types. Chemotherapy is recommended for lung cancers to control tumor growth and
to prolong patient survival. Systemic chemotherapy typically has very limited
efficacy as well as severe systemic adverse effects, which are often attributed
to the distribution of anticancer drugs to non-targeted sites. In contrast,
inhalation routes permit the delivery of drugs directly to the lungs providing
high local concentrations that may enhance the anti-tumor effect while
alleviating systemic adverse effects. Preliminary studies in animals and humans
have suggested that most inhaled chemotherapies are tolerable with manageable
pulmonary adverse effects, including cough and bronchospasm. Promoting the
deposition of anticancer drugs in tumorous cells and minimizing access to healthy
lung cells can further augment the efficacy and reduce the risk of local
toxicities caused by inhaled chemotherapy. Sustained release and tumor
localization characteristics make nanoparticle formulations a promising candidate
for the inhaled delivery of chemotherapeutic agents against lung cancers.
However, the physiology of respiratory tracts and lung clearance mechanisms
present key barriers for the effective deposition and retention of inhaled
nanoparticle formulations in the lungs. Recent research has focused on the
development of novel formulations to maximize lung deposition and to minimize
pulmonary clearance of inhaled nanoparticles. This article systematically reviews
the challenges and opportunities for the pulmonary delivery of nanoparticle
formulations for the treatment of lung cancers.
PMID- 28504257
TI - Early life factors that affect allergy development.
AB - The incidence of allergic disease continues to rise in industrialized countries.
The rapid increase in the incidence of allergic disease throughout the past half
century suggests that recently altered environmental factors are driving allergy
development. Accumulating evidence suggests that environmental experiences that
occur during the first months of life can influence the risk of allergic
sensitization. In this Review, we present the evidence relating to specific early
life exposures that affect future allergy development, and discuss how these
exposures may promote either tolerance or allergic sensitization.
PMID- 28504259
TI - Controllable cyanation of carbon-hydrogen bonds by zeolite crystals over
manganese oxide catalyst.
AB - The synthesis of organic nitriles without using toxic cyanides is in great demand
but challenging to make. Here we report an environmentally benign and cost
efficient synthesis of nitriles from the direct oxidative cyanation of primary
carbon-hydrogen bonds with easily available molecular oxygen and urea. The key to
this success is to design and synthesize manganese oxide catalysts fixed inside
zeolite crystals, forming a manganese oxide catalyst with zeolite sheath (MnOx@S
1), which exhibits high selectivity for producing nitriles by efficiently
facilitating the oxidative cyanation reaction and hindering the side hydration
reaction. The work delineates a sustainable strategy for synthesizing nitriles
while avoiding conventional toxic cyanide, which might open a new avenue for
selective transformation of carbon-hydrogen bonds.
PMID- 28504261
TI - Progressive approach to eruption at Campi Flegrei caldera in southern Italy.
AB - Unrest at large calderas rarely ends in eruption, encouraging vulnerable
communities to perceive emergency warnings of volcanic activity as false alarms.
A classic example is the Campi Flegrei caldera in southern Italy, where three
episodes of major uplift since 1950 have raised its central district by about 3 m
without an eruption. Individual episodes have conventionally been treated as
independent events, so that only data from an ongoing episode are considered
pertinent to evaluating eruptive potential. An implicit assumption is that the
crust relaxes accumulated stress after each episode. Here we apply a new model of
elastic-brittle failure to test the alternative view that successive episodes
promote a long-term accumulation of stress in the crust. The results provide the
first quantitative evidence that Campi Flegrei is evolving towards conditions
more favourable to eruption and identify field tests for predictions on how the
caldera will behave during future unrest.
PMID- 28504260
TI - New Blatter-type radicals from a bench-stable carbene.
AB - Stable benzotriazinyl radicals (Blatter's radicals) recently attracted
considerable interest as building blocks for functional materials. The existing
strategies to derivatize Blatter's radicals are limited, however, and synthetic
routes are complex. Here, we report that an inexpensive, commercially available,
analytical reagent Nitron undergoes a previously unrecognized transformation in
wet acetonitrile in the presence of air to yield a new Blatter-type radical with
an amide group replacing a phenyl at the C(3)-position. This one-pot reaction of
Nitron provides access to a range of previously inaccessible triazinyl radicals
with excellent benchtop stabilities. Mechanistic investigation suggests that the
reaction starts with a hydrolytic cleavage of the triazole ring followed by
oxidative cyclization. Several derivatives of Nitron were prepared and converted
into Blatter-type radicals to test the synthetic value of the new reaction. These
results significantly expand the scope of using functionalized benzotriazinyls as
stable radical building blocks.
PMID- 28504262
TI - Density structure of Earth's lowermost mantle from Stoneley mode splitting
observations.
AB - Advances in our understanding of Earth's thermal evolution and the style of
mantle convection rely on robust seismological constraints on lateral variations
of density. The large-low-shear-wave velocity provinces (LLSVPs) atop the core
mantle boundary beneath Africa and the Pacific are the largest structures in the
lower mantle, and hence severely affect the convective flow. Here, we show that
anomalous splitting of Stoneley modes, a unique class of free oscillations that
are perturbed primarily by velocity and density variations at the core-mantle
boundary, is explained best when the overall density of the LLSVPs is lower than
the surrounding mantle. The resolved density variations can be explained by the
presence of post-perovskite, chemical heterogeneity or a combination of the two.
Although we cannot rule out the presence of a ~100-km-thick denser-than-average
basal structure, our results support the hypothesis that LLSVPs signify large
scale mantle upwelling in two antipodal regions of the mantle.
PMID- 28504263
TI - Dehydration-driven stress transfer triggers intermediate-depth earthquakes.
AB - Intermediate-depth earthquakes (30-300 km) have been extensively documented
within subducting oceanic slabs, but their mechanics remains enigmatic. Here we
decipher the mechanism of these earthquakes by performing deformation experiments
on dehydrating serpentinized peridotites (synthetic antigorite-olivine
aggregates, minerals representative of subduction zones lithologies) at upper
mantle conditions. At a pressure of 1.1 gigapascals, dehydration of deforming
samples containing only 5 vol% of antigorite suffices to trigger acoustic
emissions, a laboratory-scale analogue of earthquakes. At 3.5 gigapascals,
acoustic emissions are recorded from samples with up to 50 vol% of antigorite.
Experimentally produced faults, observed post-mortem, are sealed by fluid-bearing
micro-pseudotachylytes. Microstructural observations demonstrate that antigorite
dehydration triggered dynamic shear failure of the olivine load-bearing network.
These laboratory analogues of intermediate-depth earthquakes demonstrate that
little dehydration is required to trigger embrittlement. We propose an
alternative model to dehydration-embrittlement in which dehydration-driven stress
transfer, rather than fluid overpressure, causes embrittlement.
PMID- 28504264
TI - Absorptive pinhole collimators for ballistic Dirac fermions in graphene.
AB - Ballistic electrons in solids can have mean free paths far larger than the
smallest features patterned by lithography. This has allowed development and
study of solid-state electron-optical devices such as beam splitters and quantum
point contacts, which have informed our understanding of electron flow and
interactions. Recently, high-mobility graphene has emerged as an ideal two
dimensional semimetal that hosts unique chiral electron-optical effects due to
its honeycomb crystalline lattice. However, this chiral transport prevents the
simple use of electrostatic gates to define electron-optical devices in graphene.
Here we present a method of creating highly collimated electron beams in graphene
based on collinear pairs of slits, with absorptive sidewalls between the slits.
By this method, we achieve beams with angular width 18 degrees or narrower, and
transmission matching classical ballistic predictions.
PMID- 28504267
TI - An in-plane magnetic chiral dichroism approach for measurement of intrinsic
magnetic signals using transmitted electrons.
AB - Electron energy-loss magnetic chiral dichroism is a powerful technique that
allows the local magnetic properties of materials to be measured quantitatively
with close-to-atomic spatial resolution and element specificity in the
transmission electron microscope. Until now, the technique has been restricted to
measurements of the magnetic circular dichroism signal in the electron beam
direction. However, the intrinsic magnetization directions of thin samples are
often oriented in the specimen plane, especially when they are examined in
magnetic-field-free conditions in the transmission electron microscope. Here, we
introduce an approach that allows in-plane magnetic signals to be measured using
electron magnetic chiral dichroism by selecting a specific diffraction geometry.
We compare experimental results recorded from a cobalt nanoplate with simulations
to demonstrate that an electron magnetic chiral dichroism signal originating from
in-plane magnetization can be detected successfully.
PMID- 28504265
TI - In vitro evolution of an influenza broadly neutralizing antibody is modulated by
hemagglutinin receptor specificity.
AB - The relatively recent discovery and characterization of human broadly
neutralizing antibodies (bnAbs) against influenza virus provide valuable insights
into antiviral and vaccine development. However, the factors that influence the
evolution of high-affinity bnAbs remain elusive. We therefore explore the
functional sequence space of bnAb C05, which targets the receptor-binding site
(RBS) of influenza haemagglutinin (HA) via a long CDR H3. We combine saturation
mutagenesis with yeast display to enrich for C05 variants of CDR H3 that bind to
H1 and H3 HAs. The C05 variants evolve up to 20-fold higher affinity but increase
specificity to each HA subtype used in the selection. Structural analysis reveals
that the fine specificity is strongly influenced by a highly conserved
substitution that regulates receptor binding in different subtypes. Overall, this
study suggests that subtle natural variations in the HA RBS between subtypes and
species may differentially influence the evolution of high-affinity bnAbs.
PMID- 28504268
TI - Observation of the universal magnetoelectric effect in a 3D topological
insulator.
AB - The electrodynamics of topological insulators (TIs) is described by modified
Maxwell's equations, which contain additional terms that couple an electric field
to a magnetization and a magnetic field to a polarization of the medium, such
that the coupling coefficient is quantized in odd multiples of alpha/4pi per
surface. Here we report on the observation of this so-called topological
magnetoelectric effect. We use monochromatic terahertz (THz) spectroscopy of TI
structures equipped with a semitransparent gate to selectively address surface
states. In high external magnetic fields, we observe a universal Faraday rotation
angle equal to the fine structure constant alpha=e2/2hc (in SI units) when a
linearly polarized THz radiation of a certain frequency passes through the two
surfaces of a strained HgTe 3D TI. These experiments give insight into axion
electrodynamics of TIs and may potentially be used for a metrological definition
of the three basic physical constants.
PMID- 28504266
TI - Low phosphate activates STOP1-ALMT1 to rapidly inhibit root cell elongation.
AB - Environmental cues profoundly modulate cell proliferation and cell elongation to
inform and direct plant growth and development. External phosphate (Pi)
limitation inhibits primary root growth in many plant species. However, the
underlying Pi sensory mechanisms are unknown. Here we genetically uncouple two Pi
sensing pathways in the root apex of Arabidopsis thaliana. First, the rapid
inhibition of cell elongation in the transition zone is controlled by
transcription factor STOP1, by its direct target, ALMT1, encoding a malate
channel, and by ferroxidase LPR1, which together mediate Fe and peroxidase
dependent cell wall stiffening. Second, during the subsequent slow inhibition of
cell proliferation in the apical meristem, which is mediated by LPR1-dependent,
but largely STOP1-ALMT1-independent, Fe and callose accumulate in the stem cell
niche, leading to meristem reduction. Our work uncovers STOP1 and ALMT1 as a
signalling pathway of low Pi availability and exuded malate as an unexpected
apoplastic inhibitor of root cell wall expansion.
PMID- 28504270
TI - Antiplatelet therapy: New score for predicting bleeding risk after DAPT.
PMID- 28504269
TI - YAP regulates cell mechanics by controlling focal adhesion assembly.
AB - Hippo effectors YAP/TAZ act as on-off mechanosensing switches by sensing
modifications in extracellular matrix (ECM) composition and mechanics. The
regulation of their activity has been described by a hierarchical model in which
elements of Hippo pathway are under the control of focal adhesions (FAs). Here we
unveil the molecular mechanism by which cell spreading and RhoA GTPase activity
control FA formation through YAP to stabilize the anchorage of the actin
cytoskeleton to the cell membrane. This mechanism requires YAP co-transcriptional
function and involves the activation of genes encoding for integrins and FA
docking proteins. Tuning YAP transcriptional activity leads to the modification
of cell mechanics, force development and adhesion strength, and determines cell
shape, migration and differentiation. These results provide new insights into the
mechanism of YAP mechanosensing activity and qualify this Hippo effector as the
key determinant of cell mechanics in response to ECM cues.
PMID- 28504271
TI - Probing nanofriction and Aubry-type signatures in a finite self-organized system.
AB - Friction in ordered atomistic layers plays a central role in various nanoscale
systems ranging from nanomachines to biological systems. It governs transport
properties, wear and dissipation. Defects and incommensurate lattice constants
markedly change these properties. Recently, experimental systems have become
accessible to probe the dynamics of nanofriction. Here, we present a model system
consisting of laser-cooled ions in which nanofriction and transport processes in
self-organized systems with back action can be studied with atomic resolution. We
show that in a system with local defects resulting in incommensurate layers,
there is a transition from sticking to sliding with Aubry-type signatures. We
demonstrate spectroscopic measurements of the soft vibrational mode driving this
transition and a measurement of the order parameter. We show numerically that
both exhibit critical scaling near the transition point. Our studies demonstrate
a simple, well-controlled system in which friction in self-organized structures
can be studied from classical- to quantum-regimes.
PMID- 28504274
TI - Link between light-triggered Mg-banding and chamber formation in the planktic
foraminifera Neogloboquadrina dutertrei.
AB - The relationship between seawater temperature and the average Mg/Ca ratios in
planktic foraminifera is well established, providing an essential tool for
reconstructing past ocean temperatures. However, many species display alternating
high and low Mg-bands within their shell walls that cannot be explained by
temperature alone. Recent experiments demonstrate that intrashell Mg variability
in Orbulina universa, which forms a spherical terminal shell, is paced by the
diurnal light/dark cycle. Whether Mg-heterogeneity is also diurnally paced in
species with more complex shell morphologies is unknown. Here we show that high
Mg/Ca-calcite forms at night in cultured specimens of the multi-chambered species
Neogloboquadrina dutertrei. Our results demonstrate that N. dutertrei adds a
significant amount of calcite, and nearly all Mg-bands, after the final chamber
forms. These results have implications for interpreting patterns of calcification
in N. dutertrei and suggest that diurnal Mg-banding is an intrinsic component of
biomineralization in planktic foraminifera.
PMID- 28504273
TI - Legionella effector Lpg1137 shuts down ER-mitochondria communication through
cleavage of syntaxin 17.
AB - During infection of macrophages, the pathogenic bacterium Legionella pneumophila
secretes effector proteins that induce the conversion of the plasma membrane
derived vacuole into an endoplasmic reticulum (ER)-like replicative vacuole.
These ER-like vacuoles are ultimately fused with the ER, where the pathogen
replicates. Here we show that the L. pneumophila effector Lpg1137 is a serine
protease that targets the mitochondria and their associated membranes. Lpg1137
binds to and cleaves syntaxin 17, a soluble N-ethylmaleimide-sensitive factor
attachment protein receptor (SNARE) protein that is known to participate in the
regulation of mitochondrial dynamics through interaction with the mitochondrial
fission factor Drp1 in fed cells and in autophagy through interaction with Atg14L
and other SNAREs in starved cells. Cleavage of syntaxin 17 inhibits not only
autophagy but also staurosporine-induced apoptosis occurring in a Bax, Drp1
dependent manner. Thus, L. pneumophila can shut down ER-mitochondria
communication through cleavage of syntaxin 17.
PMID- 28504272
TI - Sirt1 carboxyl-domain is an ATP-repressible domain that is transferrable to other
proteins.
AB - Sirt1 is an NAD+-dependent protein deacetylase that regulates many physiological
functions, including stress resistance, adipogenesis, cell senescence and energy
production. Sirt1 can be activated by energy deprivation, but the mechanism is
poorly understood. Here, we report that Sirt1 is negatively regulated by ATP,
which binds to the C-terminal domain (CTD) of Sirt1. ATP suppresses Sirt1
activity by impairing the CTD's ability to bind to the deacetylase domain as well
as its ability to function as the substrate recruitment site. ATP, but not NAD+,
causes a conformational shift to a less compact structure. Mutations that prevent
ATP binding increase Sirt1's ability to promote stress resistance and inhibit
adipogenesis under high-ATP conditions. Interestingly, the CTD can be attached to
other proteins, thereby converting them into energy-regulated proteins. These
discoveries provide insight into how extreme energy deprivation can impact Sirt1
activity and underscore the complex nature of Sirt1 structure and regulation.
PMID- 28504275
TI - Transcriptomic and macroevolutionary evidence for phenotypic uncoupling between
frog life history phases.
AB - Anuran amphibians undergo major morphological transitions during development, but
the contribution of their markedly different life-history phases to
macroevolution has rarely been analysed. Here we generate testable predictions
for coupling versus uncoupling of phenotypic evolution of tadpole and adult life
history phases, and for the underlying expression of genes related to
morphological feature formation. We test these predictions by combining evidence
from gene expression in two distantly related frogs, Xenopus laevis and
Mantidactylus betsileanus, with patterns of morphological evolution in the entire
radiation of Madagascan mantellid frogs. Genes linked to morphological structure
formation are expressed in a highly phase-specific pattern, suggesting uncoupling
of phenotypic evolution across life-history phases. This gene expression pattern
agrees with uncoupled rates of trait evolution among life-history phases in the
mantellids, which we show to have undergone an adaptive radiation. Our results
validate a prevalence of uncoupling in the evolution of tadpole and adult
phenotypes of frogs.
PMID- 28504277
TI - Role of dietary onion in modifying the faecal bile acid content in rats fed a
high-cholesterol diet.
AB - The determination of faecal bile patterns offers new opportunities in the search
for non-invasive biomarkers of disease status. The objective of this study was to
describe the shifts in faecal bile acid (BA) composition induced by feeding a
high-cholesterol/cholic acid diet (HC) over 7 weeks of experimental feeding in
Wistar rats, and to evaluate the effect of onion included as a functional
ingredient (HCO). A HPLC-MS/MS method allowed the detection of 29 bile acids, 10
of which were tentatively identified and 12 confirmed and quantified by means of
standards and calibration curves. The excretion of bile acids revealed a
discriminating bile acid profile between the HC and HCO groups compared with the
C group. HCO feeding indicated significant changes in specific primary and
secondary BA in both the unconjugated and conjugated forms caused by the addition
of the onion ingredient to the diet. The results suggest that the induction of
microbiome modifications by the HC and HCO diets acts as a critical modifier of
the faecal bile acid composition. These modifications might reflect and be linked
to changes in the reabsorption of BA at an intestinal level and the process of BA
deconjugation in the course of hypercholesterolemia.
PMID- 28504278
TI - High-frequency linear rheology of hydrogels probed by ultrasound-driven
microbubble dynamics.
AB - Ultrasound-driven microbubble dynamics are central to biomedical applications,
from diagnostic imaging to drug delivery and therapy. In therapeutic
applications, the bubbles are typically embedded in tissue, and their dynamics
are strongly affected by the viscoelastic properties of the soft solid medium.
While the behaviour of bubbles in Newtonian fluids is well characterised, a
fundamental understanding of the effect on ultrasound-driven bubble dynamics of a
soft viscoelastic medium is still being developed. We characterised the resonant
behaviour in ultrasound of isolated microbubbles embedded in agarose gels,
commonly used as tissue-mimicking phantoms. Gels with different viscoelastic
properties were obtained by tuning agarose concentration, and were characterised
by standard rheological tests. Isolated bubbles (100-200 MUm) were excited by
ultrasound (10-50 kHz) at small pressure amplitudes (<1 kPa), to ensure that the
deformation of the material and the bubble dynamics remained in the linear
regime. The radial dynamics of the bubbles were recorded by high-speed video
microscopy. Resonance curves were measured experimentally and fitted to a model
combining the Rayleigh-Plesset equation governing bubble dynamics, with the
Kelvin-Voigt model for the viscoelastic medium. The resonance frequency of the
bubbles was found to increase with increasing shear modulus of the medium, with
implications for optimisation of imaging and therapeutic ultrasound protocols. In
addition, the viscoelastic properties inferred from ultrasound-driven bubble
dynamics differ significantly from those measured at low frequency with the
rheometer. Hence, rheological characterisation of biomaterials for medical
ultrasound applications requires particular attention to the strain rate applied.
PMID- 28504276
TI - Targeted calcium influx boosts cytotoxic T lymphocyte function in the tumour
microenvironment.
AB - Adoptive cell transfer utilizing tumour-targeting cytotoxic T lymphocytes (CTLs)
is one of the most effective immunotherapies against haematological malignancies,
but significant clinical success has not yet been achieved in solid tumours due
in part to the strong immunosuppressive tumour microenvironment. Here, we show
that suppression of CTL killing by CD4+CD25+Foxp3+ regulatory T cell (Treg) is in
part mediated by TGFbeta-induced inhibition of inositol trisphosphate (IP3)
production, leading to a decrease in T cell receptor (TCR)-dependent
intracellular Ca2+ response. Highly selective optical control of Ca2+ signalling
in adoptively transferred CTLs enhances T cell activation and IFN-gamma
production in vitro, leading to a significant reduction in tumour growth in mice.
Altogether, our findings indicate that the targeted optogenetic stimulation of
intracellular Ca2+ signal allows for the remote control of cytotoxic effector
functions of adoptively transferred T cells with outstanding spatial resolution
by boosting T cell immune responses at the tumour sites.
PMID- 28504279
TI - The structural impact of water sorption on device-quality melanin thin films.
AB - The melanins are a class of pigmentary bio-macromolecules ubiquitous in the
biosphere. They possess an intriguing set of physico-chemical properties and have
been shown to exhibit hybrid protonic-electronic electrical conductivity, a
feature derived from a process termed chemical self-doping driven by the sorption
of water. Although the mechanism underlying the electrical conduction has been
established, how the sorbed water interacts with the melanin structure at the
physical level has not. Herein we use neutron reflectometry to study changes in
the structure of synthetic melanin thin films as a function of H2O and D2O vapour
pressure. Water is found to be taken up evenly throughout the films, and by
employing the contrast effect, the existence of labile protons through reversible
deuterium exchange is demonstrated. Finally, we determine a sorption isotherm to
enable quantification of the melanin-water interactions.
PMID- 28504284
TI - Fabrication and characterization of self-folding thermoplastic sheets using
unbalanced thermal shrinkage.
AB - Self-folding or micro-origami technologies are actively investigated as a novel
manufacturing process to fabricate three-dimensional macro/micro-structures. In
this paper, we present a simple process to produce a self-folding structure with
a biaxially oriented polystyrene sheet (BOPS) or Shrinky Dinks. A BOPS sheet is
known to shrink to one-third of its original size in plane, when it is heated
above 160 degrees C. A grid pattern is engraved on one side of the BOPS film
with a laser engraver to decrease the thermal shrinkage of the engraved side. The
thermal shrinkage of the non-engraved side remains the same and this unbalanced
thermal shrinkage causes folding of the structure as the structure shrinks at
high temperature. We investigated the self-folding mechanism and characterized
how the grid geometry, the grid size, and the power of the laser engraver affect
the bending curvature. The developed fabrication process to locally modulate
thermomechanical properties of the material by engraving the grid pattern and the
demonstrated design methodology to harness the unbalanced thermal shrinkage can
be applied to develop complicated self-folding macro/micro structures.
PMID- 28504285
TI - A van der Waals DFT study of chain length dependence of alkanethiol adsorption on
Au(111): physisorption vs. chemisorption.
AB - The energetics and structures of physisorbed and chemisorbed alkanethiols on
Au(111) have been systematically investigated up to 10 carbon atoms using van der
Waals (vdW) corrected density functional theory (DFT) calculations. The role of
chain length, tilting angle and coverage on the adsorption characteristics has
been examined to elucidate the energetics and plausible transformation mechanisms
between lying down and standing up phases. Coverage and size dependent chain
chain electronic interactions counteract with the alkyl chain-gold surface
interactions and the surface relaxation of the metal in the formation of standing
up monolayer structures. For the striped phases of long chain alkanethiols,
however, our calculations on decanethiol indicate alkyl chain-gold surface
interactions to be strong enough to force the molecule to be perfectly parallel
to the surface by lifting a gold atom up, in agreement with the proposed models
for this film in the literature.
PMID- 28504280
TI - Metabolic profile and underlying improved bio-activity of Fructus aurantii
immaturus by human intestinal bacteria.
AB - Fructus aurantii immaturus (FAI) is the dried young fruit of Citrus aurantium L.
or Citrus sinensis L. Osbeck. The purpose of this paper was to investigate the
metabolic fate of FAI upon incubation with human intestinal bacteria, meanwhile
to evaluate the antioxidant and anti-inflammatory activities of FAI and the
transformed Fructus aurantii immaturus (TFAI). The water extract of FAI was
anaerobically incubated with human intestinal bacterial suspensions for 48 h at
37 degrees C. Liquid chromatography-hybridised with quadrupole-time-of-flight
mass spectrometry (LC-Q-TOF/MS) was applied to identify FAI metabolites. A total
of 45 compounds were identified in FAI, eleven of which were metabolized by human
intestinal bacteria. Nine major metabolites were identified as eriodictyol,
naringenin, hesperetin, luteolin, apigenin, chryseriol, isosakuranetin, phloretin
and diosmetin. The metabolic profile of FAI was elucidated on the basis of
metabolite information. We found that the concentrations of acetic, propionic and
butyric acids in FAI culture were all increased during fermentation relative to
those of the control. Further bioactive evaluations showed that TFAI exhibited
more potent antioxidant and anti-inflammatory abilities than FAI in vitro.
Additionally, in vivo experiment confirmed that FAI significantly attenuated the
blood endotoxin and TNF-alpha levels in the conventional rats compared to those
of pseudo-germ-free (PGF) rats. This study revealed that metabolites may play a
key role in the antioxidant and anti-inflammatory capacities of FAI.
PMID- 28504286
TI - Ag-Catalyzed difluorohydration of beta-alkynyl ketones for diastereoselective
synthesis of 1,5-dicarbonyl compounds.
AB - A new catalytic difluorohydration of beta-alkynyl ketones using NFSI as the
fluorinating reagent has been established, diastereoselectively furnishing a
range of structurally diverse difluoride 1,5-dicarbonyl products through C(sp3)-H
fluorination. Notably, the sterically encumbered t-butyl functionality located at
the alpha-position of the carbonyl group of substrates 1 showed excellent
diastereoselectivity (up to >99 : 1 dr). The reaction enabled multiple bond
forming events including two C(sp3)-F formation through Ag-catalysis to provide a
highly efficient and practical method toward difluoride 1,5-dicarbonyls, some of
which were successfully converted into difluorinated isoquinolines.
PMID- 28504287
TI - gamma-Oryzanol nanoemulsions produced by a low-energy emulsification method: an
evaluation of process parameters and physicochemical stability.
AB - gamma-Oryzanol is a natural antioxidant and nutraceutical compound, which makes
it a good candidate for nutraceuticals, food supplements and pharmaceutical
preparations. However, the incorporation of gamma-oryzanol into aqueous
formulations is rather difficult and its bioavailability can be severely
decreased because of its water-insoluble property. In this study, gamma-oryzanol
enriched nanoemulsion based fish oil and medium-chain triglyceride as carrier
oils were proposed. The main objective was to optimize process parameters to form
stable nanoemulsions and evaluate their physicochemical stability. The
formulations of stable gamma-oryzanol nanoemulsions were composed of 10% mixed
carrier oils (weight ratio of fish oil to medium-chain triglyceride = 3 : 7) and
10% mixed surfactants (weight ratio of Tween 80 to Span 20 = 3 : 1). The
nanoemulsions were stable at a broad pH range of 2-7 and high salt concentrations
(<=0.8 mol L-1) and sucrose levels (<=16%). The nanoemulsions were much more
stable at heating temperatures below 50 degrees C than at elevated heating
temperatures (60 and 70 degrees C). The nanoemulsions maintained their physical
stability at various storage temperatures (5-37 degrees C) for 18 days.
Nanoemulsions at 5 and 23 degrees C had lower peroxide values and anisidine
values than those at an elevated storage temperature (37 degrees C). These
results demonstrate that the low-energy emulsification method can produce gamma
oryzanol-enriched nanoemulsions using fish oil and medium-chain triglyceride as
carrier oils, and provide useful information for producing bioactive lipids
loaded nanoemulsions for food systems, personal care and pharmaceutical products.
PMID- 28504288
TI - Understanding nanoparticle porosity via nanoimpacts and XPS: electro-oxidation of
platinum nanoparticle aggregates.
AB - The porosity of platinum nanoparticle aggregates (PtNPs) is investigated
electrochemically via particle-electrode impacts and by XPS. The mean charge per
oxidative transient is measured from nanoimpacts; XPS shows the formation of PtO
and PtO2 in relative amounts defined by the electrode potential and an average
oxidation state is deduced as a function of potential. The number of platinum
atoms oxidised per PtNP is calculated and compared with two models: solid and
porous spheres, within which there are two cases: full and surface oxidation.
This allows insight into extent to which the internal surface of the aggregate is
'seen' by the solution and is electrochemically active.
PMID- 28504289
TI - An ionic coordination hybrid hydrogel for bioseparation.
AB - An ionic coordination hybrid hydrogel is formed with ionic and covalent
crosslinked networks via one-step copolymation. It is demonstrated that the
hybrid crosslinker gel is used as a separation matrix for bioseparation, showing
high separation efficiency, in contrast to traditional polyacrylamide gels. The
hydrogel might serve as a novel matrix for bioseparation.
PMID- 28504290
TI - Effect of body deformability on microswimming.
AB - In this work we consider the following question: given a mechanical microswimming
mechanism, does increased deformability of the swimmer body hinder or promote the
motility of the swimmer? To answer this we run immersed-boundary-lattice
Boltzmann simulations of a microswimmer composed of deformable beads connected
with springs. We find that the same deformations in the beads can result in
different effects on the swimming velocity, namely an enhancement or a reduction,
depending on the other parameters. To understand this we determine analytically
the velocity of the swimmer, starting from the forces driving the motion and
assuming that the deformations in the beads are known as functions of time and
are much smaller than the beads themselves. We find that to the lowest order,
only the driving frequency mode of the surface deformations contributes to the
swimming velocity, and comparison to the simulations shows that both the velocity
promoting and velocity-hindering effects of bead deformability are reproduced
correctly by the theory in the limit of small bead deformations. For the case of
active deformations we show that there are critical values of the spring constant
- which for a general swimmer corresponds to its main elastic degree of freedom -
which decide whether the body deformability is beneficial for motion or not.
PMID- 28504291
TI - Strain-induced stiffening of nanocellulose-reinforced poly(vinyl alcohol)
hydrogels mimicking collagenous soft tissues.
AB - Soft tissues possess remarkable mechanical strength for their high water content,
which is hard to mimic in synthetic materials. Here, we demonstrate how strain
induced stiffening in hydrogels plays a major role in mimicking the mechanical
properties of collagenous soft tissues. In particular, nanocellulose reinforced
polyvinyl alcohol (PVA) hydrogels of exceptionally high water content (90-93 wt%)
are shown to exhibit collagen-like mechanical behavior typical for soft tissues.
High water content and co-existence of both soft and rigid domains in the gel
network are the main factors responsible for strain-induced stiffening. This
observed effect due to the alignment of rigid components of the hydrogel is
simulated through modeling and visualized through strain-induced birefringence
experiments. Design parameters such as nanocellulose aspect ratio and solvent
composition are also shown to be important to control the mechanical properties.
In addition, owing to their transparency (90-95% at 550 nm) and hyperelastic
properties (250-350% strain), the described hydrogels are promising materials for
biomedical applications, especially in ophthalmology.
PMID- 28504292
TI - Microstructure degradation of Ni/CGO anodes for solid oxide fuel cells after long
operation time using 3D reconstructions by FIB tomography.
AB - Solid oxide fuel cells (SOFCs) are electrochemical conversion devices, which
essentially consist of two porous electrodes separated by a dense, oxide ion
conducting electrolyte. The performance and the durability of SOFCs strongly
depend on the electrode microstructure. In this paper, the impact of a relatively
long exposure time (up to 20 000 h) under realistic operation terms (temperature
(T) = 850 degrees C, current density (J) = 190-250 mA cm-2) in the kinetics of
microstructural degradation are investigated for porous nickel (Ni)/ceria
gadolinium oxide (CGO) anodes, to understand the microstructural evolution in
SOFC cermet anodes. A combined system of Focused Ion Beam (FIB) and Scanning
Electron Microscope (SEM) tomography was used to analyze various anode
microstructures aged during different operating times (2500 h, 15 000 h and 20
000 h). The methodologies of image acquisition as well as the segmentation and
the object recognition were improved, offering a reliable quantification of Ni
grain growth, connectivity, tortuosity factor and triple phase boundary length
(TPBL). The representative volume element (RVE) was also studied, and its
dependence on aging time was confirmed. To construct a volume that can be
accurate and representative for the whole sample, the necessary corresponding 3D
reconstruction size was adjusted by increasing operating time, in order to
suppress the influence of microstructure variation caused by Ni and CGO
agglomeration. Statistically significant 3D microstructural changes were observed
in the anode by increasing the operating time, including nickel particle size
distribution, changes in connectivity of the ceramic part (CGO) and a significant
decrease of contiguous triple phase boundary densities. Additional qualitative
observations were done in order to gain a complete insight of the degradation
phenomena in nickel based cermet anodes.
PMID- 28504293
TI - Quantifying the sensitivity of the network structure and properties from
simultaneous measurements during photopolymerization.
AB - We present a method that combines experimental and computational approaches to
assess a comprehensive set of structural and functional evolution during a
network formation process via photopolymerization. Our work uses the simultaneous
measurement of the degree of conversion, polymerization stress, the change in
reaction temperature, and shrinkage strain in situ. These measurements are
combined with the theory of viscoelastic materials to deduce the relaxation time
and frequency-dependent modulus of the polymerizing network. The relaxation time
and degree of conversion are used to demonstrate the effect of processing
parameters (e.g. curing protocol adjusted by the light intensity) in creating
different network structures for the same initial resin. We describe experimental
trends using effective medium calculations on a cross-linked polymer network
model. In particular, we show that the effect of curing conditions on the spatial
heterogeneity in crosslink density can be quantified using multiparametric
measurements and modeling. Collectively, the present method is a way to examine
holistically the complex structural and functional evolution of the network
formation process.
PMID- 28504295
TI - Increased permeability of oxygen atoms through graphene with ripples.
AB - Graphene is an ideal membrane for selective separation because of its unique
properties and single-layer structure. Considerable efforts have been made to
alter the permeability of graphene. In this study, we investigate the pathways
for an oxygen atom to pass through graphene sheets. We also identify the effect
of the ripple's curvature in graphene sheets on the energy barrier of permeation
through density functional theory calculations. Results show that oxygen atoms
can easily pass through the concave side of graphene ripples with a large
curvature. The analysis of transition states reveals that the space where an
oxygen atom passes through keeps an almost identical structure with similar bond
lengths regardless of the curvature. We find that the Cu(111) substrate may draw
out the C-C bond lengths of graphene at the Cu(111) surface because of the strong
interaction between the graphene edge and copper atoms. Consequently, the energy
barrier of the permeation of oxygen atoms through graphene is reduced. These
results suggest that the rippling of graphene significantly affects its
permeation.
PMID- 28504294
TI - Ultrasensitive fluorescence detection of transcription factors based on
kisscomplex formation and the T7 RNA polymerase amplification method.
AB - Herein, we report a kisscomplex based protein fluorescence assay (KPFA) method,
which employed the formation of a kisscomplex and the T7 RNA polymerase
amplification method, for the assay of transcription factors with high
sensitivity.
PMID- 28504296
TI - Supplementation with n-3, n-6, n-9 fatty acids in an insulin-resistance animal
model: does it improve VLDL quality?
AB - : Insulin-resistance (IR), of increased cardiovascular risk, is characterized by
the production of altered VLDL with greater atherogenicity. Dietary fatty acids
influence the type of circulating VLDL. But, it is not clear how dietary fatty
acids impact VLDL characteristics in IR. AIM: to evaluate the effects of n-3, n-6
and n-9 fatty acid supplementation on preventing atherogenic alterations in VLDL,
in a diet-induced IR rat model. Male Wistar rats (180-200 g) were fed: standard
diet (control, n = 8) and a sucrose rich diet (30% sucrose in water/12 weeks,
SRD; n = 24). Simultaneously, SRD was subdivided into SRD-C (standard diet), and
three other groups supplemented (15% w/w) with: fish oil (SRD-n3), sunflower oil
(SRD-n6) and high oleic sunflower oil (SRD-n9). Lipid profile, free fatty acids,
glucose, and insulin were measured. Isolated VLDL (d < 1.006 g ml-1) was
characterized by chemical composition and size (size exclusion-HPLC). In
comparison with SRD-C: SRD-n3 showed an improved lipoprotein profile (p < 0.01),
with lower levels of insulin and HOMA-IR (p < 0.05). SRD-n6 showed increased
levels of HDL-cholesterol and lower insulin levels. SRD-n9 did not exhibit
differences in lipid and IR profile, and even favored weight gain and visceral
fat. Only SRD-n3 prevented the alterations in VLDL-TG% (54.2 +/- 4.4% vs. 68.6 +/
8.2, p < 0.05) and showed lower large VLDL-% (22.5[19.7-35.6] vs. 49.1[15.5
82.0], p < 0.05), while SRD-n6 and SRD-n9 did not show effects. CONCLUSION: In
IR, while n-3 PUFA showed expected favorable effects, supplementation with n-6
PUFA and n-9 MUFA did not prevent atherogenic alterations of VLDL. Thus, the
recommendations of supplementation with these fatty acids in general diet should
be revised.
PMID- 28504297
TI - Elemental bioimaging by means of LA-ICP-OES: investigation of the calcium, sodium
and potassium distribution in tobacco plant stems and leaf petioles.
AB - Laser ablation-inductively coupled plasma-optical emission spectroscopy (LA-ICP
OES) is presented as a valuable tool for elemental bioimaging of alkali and earth
alkali elements in plants. Whereas LA-ICP-OES is commonly used for micro analysis
of solid samples, laser ablation-inductively coupled plasma-mass spectrometry (LA
ICP-MS) has advanced to the gold standard for bioimaging. However, especially for
easily excitable and ubiquitous elements such as alkali and earth alkali
elements, LA-ICP-OES holds some advantages regarding simultaneous detection,
costs, contamination, and user-friendliness. This is demonstrated by determining
the calcium, sodium and potassium distribution in tobacco plant stem and leaf
petiole tissues. A quantification of the calcium contents in a concentration
range up to 1000 MUg g-1 using matrix-matched standards is presented as well. The
method is directly compared to a LA-ICP-MS approach by analyzing parallel slices
of the same samples.
PMID- 28504298
TI - Bio-inspired hierarchical micro- and nano-wrinkles obtained via mechanically
directed self-assembly on shape-memory polymers.
AB - Inspired by complex multi-functional leaf and petal surfaces, we introduce a
mechanically directed self-assembly process to create linearly oriented micro-
and nanosized surface wrinkles in an all-polymer bi-layer system based on a shape
memory polymer substrate. By systematically investigating the influence of
coating thickness and substrate programming strain on wrinkle period and height,
we reveal how to control the structure size from a few hundred nanometers up to
several microns. As a parameter unique to shape memory polymers, we demonstrate
that the temperature during the recovery process can also be utilized to tailor
the structure dimensions. Furthermore, we advance the method with a second
structuring step to mimic the hierarchically structured petal surfaces of tulips
and daisies. The presented structuring method provides a large-scale, mold-free,
and very cost-effective way for the full-polymer fabrication of micro and sub
microstructures with adjustable structure size and intrinsic irregularity.
PMID- 28504300
TI - Effect of protection against hot climate on growth performance, physiological
response and endocrine profile of growing lambs under semi-arid tropical
environment.
AB - In the hot semi-arid tropical region, extreme summer is a major constraint in
sheep production. The growth performance of growing lambs is impaired during the
summer. Therefore, the present study was conducted to assess the effect of
protection against hot climate on growth performance, physiological response, and
endocrine profile of growing lambs under semi-arid tropical environment. All the
data in the experiment were presented as mean +/- SE. Thirty Malpura lambs with
the age of 122.7 +/- 6.05 days and body weight of 19.52 +/- 0.42 kg were allotted
into three groups, viz. G1 (control, lambs kept in open area under tree shade),
G2 (lambs kept in conventional asbestos-roofed shed), and G3 (lambs kept in
designed shed). The allotment was based on their initial body weight so that the
mean body weight of each group was similar. In all three types of protection,
lambs were provided with sufficient space to move and social interaction. In
asbestos-roofed shed (G2), all the four sides from ground to the roof were fenced
with strong galvanized iron chain link. But in G3, all the four sides were
constructed in a manner that there was 0.13 m air space between inner and outer
solid brick columns of the wall up to 1.37 m height, and rest up to the roof was
fenced with bamboo splint net. The air space between the two columns of the wall
was filled with sand, and it was kept in moist condition by continuous water
drips which provide extra evaporative cooling. The designed shed was basically
constructed with bamboo. Tree shade was assured under the natural shades of large
trees. The shaded area was protected by wire fences. The experiment was conducted
for 45 days during very high temperature (May-June). The lambs were provided with
ad libitum green fodder, dry roughage, 300 g concentrate, and ad libitum drinking
water. The respiration rate at morning and afternoon, pulse rate at morning and
afternoon and rectal temperature at afternoon was significantly (P < 0.05) lower
in lambs of G3 as compared to other groups. The final body weight did not differ
significantly between the groups, but average daily gain (g/day) was higher in G3
(150.06 +/- 11.13) as compared to the G1 (109.69 +/- 18.10). The feed conversion
rate (FCR) was significantly (P < 0.05) better in G3 (5.49 +/- 0.08) as compared
to G1 (7.65 +/- 0.08) and G2 (6.60 +/- 0.08). The hemoglobin level was
significantly (P < 0.05) higher in G1. The endocrine profile did not vary
significantly (P > 0.05) among the groups, but insulin-like growth factor-1 (IGF
1) was higher in G3. It can be concluded from this study the lambs provided with
better protection during summer remained in more comfortable condition, showed
better FCR, and although not statistically significant showed better growth
performance.
PMID- 28504302
TI - Guidance to the International Medical Guide for Ships 3rd edition.
PMID- 28504299
TI - What We Know About Stage II and III Colon Cancer: It's Still Not Enough.
AB - The introduction of oxaliplatin as adjuvant treatment for stage III colon cancer
in 2004 has been the last practice changing progress in adjuvant treatment for
patients with early colon cancer. Since then, many prognostic and predictive
biomarkers have been studied, but only DNA mismatch repair status has been
validated as having an important prognostic value. Accordingly, TNM and clinical
pathological patterns, such as pT4 lesions and lymph node sampling <12 nodes, are
the main factors that guide physicians' choice regarding adjuvant treatment. More
recently, many biomarkers showed promising results: POLE, ErbB2, CDX2, SMAD4,
BRAF and KRAS. In addition to these, immune-contexture, molecular classification,
and gene signatures could become new ways to better classify colon cancer
patients with more discriminatory power than TNM. The aim of this review is to
report the state-of-the-art of prognostic and predictive factors in the adjuvant
setting and which of these could modify clinical practice and maybe replace TNM
classification.
PMID- 28504301
TI - First report on serological evidence of bovine viral diarrhea virus (BVDV)
infection in farmed and free ranging mithuns (Bos frontalis).
AB - Despite reports of BVDV infection in several domestic and wild ruminants, no
information exists for mithun (Bos frontalis) species. Hence, this study was
undertaken to determine prevalence of BVDV infection in mithuns, which contribute
significantly to local economy in the North Eastern region of India. Blood and
serum samples were collected between 2013 and 2016 from mithuns (n = 466)
belonging to the states of Nagaland, Mizoram, and Arunachal Pradesh. Serum
samples were tested for BVDV antibodies by a commercial ELISA and leukocytes were
tested for BVDV by real-time RT-PCR. The overall true seroprevalence rate was
13.1% (95% confidence interval, CI: 6.9-17.8%) with higher prevalence in mithuns
reared under semi-intensive system (27.5%) than in free-ranging mithuns (7.6%).
Among the three states, seroprevalence (16.2%) was highest in Nagaland, while
prevalence rates varied markedly among geographical locations. Age-wise data
showed highest seroprevalence rate in >6-year-old animals (20.6%) than 2-6 years
old (16.9%), 6 months-2 years old (8.5%), and <6-month-old animals (11.3%). The
seroprevalence was higher in males (20.9%) than in females (12.1%). Among the
four mithun strains, higher prevalence was evident in Manipur (30.3%) than
Arunachal (21.3%), Nagaland (11.7%), and Mizoram strain (10.2%). However, no BVDV
genomic RNA could be detected. The results provide first serological evidence of
BVDV infection in mithun species and extend the knowledge on BVDV host range. The
baseline data will help further investigations on epidemiology of BVD in mithun
and its impact on mithun production.
PMID- 28504303
TI - Distracted Walking, Bicycling, and Driving: Systematic Review and Meta-Analysis
of Mobile Technology and Youth Crash Risk.
AB - This article examined the impact of mobile technology on young pedestrians,
bicyclists, and drivers. A systematic search yielded 41 articles meeting
inclusion criteria: peer-reviewed, published before February 1, 2016, behavioral
outcome related to pedestrian, bicycling, or driving in the presence of mobile
technology use, youth sample. Eleven studies were meta-analyzed to evaluate
increased risk for crash/near-crash while distracted. Risk of bias and quality of
research were assessed. Across methodologies, developmental stages, and type of
distracting task, mobile technology use impairs youth safety on the road. Quality
of evidence was low (pedestrian) to moderate (driving). Findings are discussed
from the perspective of cognitive and visual distractions. Policy and behavioral
efforts should continue to reduce mobile technology use in transportation
settings.
PMID- 28504304
TI - Exploiting scavenger receptors in cancer immunotherapy: Lessons from CD5 and SR
B1.
AB - Scavenger receptors (SRs) are structurally heterogeneous cell surface receptors
characterized by their capacity to remove extraneous or modified self
macromolecules from circulation, thus avoiding the accumulation of noxious agents
in the extracellular space. This scavenging activity makes SRs important
molecules for host defense and homeostasis. In turn, SRs keep the activation of
the steady-state immune response in check, and participate as co-receptors in the
priming of the effector immune responses when the macromolecules are associated
with a threat that might compromise host homeostasis. Therefore, SRs built up
sophisticated sensor mechanisms controlling the immune system, which may be
exploited to develop novel drugs for cancer immunotherapy. In this review, we
focus on the regulation of the anti-tumor immune response by two paradigmatic
SRs: the lymphocyte receptor CD5 and the more broadly distributed scavenger
receptor class B type 1 (SR-B1). Cancer immunity can be boosted by blockade of
SRs working as immune checkpoint inhibitors (CD5) and/or by proper engagement of
SRs working as innate danger receptor (SR-B1). Thus, these receptors illustrate
both the complexity of targeting SRs in cancer immunotherapy and also the
opportunities offered by such an approach.
PMID- 28504306
TI - Crystal structure of the Entamoeba histolytica RNA lariat debranching enzyme
EhDbr1 reveals a catalytic Zn2+ /Mn2+ heterobinucleation.
AB - The RNA lariat debranching enzyme, Dbr1, is a metallophosphoesterase that cleaves
2'-5' phosphodiester bonds within intronic lariats. Previous reports have
indicated that Dbr1 enzymatic activity is supported by diverse metal ions
including Ni2+ , Mn2+ , Mg2+ , Fe2+ , and Zn2+ . While in initial structures of
the Entamoeba histolytica Dbr1 only one of the two catalytic metal-binding sites
were observed to be occupied (with a Mn2+ ion), recent structures determined a
Zn2+ /Fe2+ heterobinucleation. We solved a high-resolution X-ray crystal
structure (1.8 A) of the E. histolytica Dbr1 and determined a Zn2+ /Mn2+
occupancy. ICP-AES corroborate this finding, and in vitro debranching assays with
fluorescently labeled branched substrates confirm activity.
PMID- 28504305
TI - Intranuclear and higher-order chromatin organization of the major histone gene
cluster in breast cancer.
AB - Alterations in nuclear morphology are common in cancer progression. However, the
degree to which gross morphological abnormalities translate into compromised
higher-order chromatin organization is poorly understood. To explore the
functional links between gene expression and chromatin structure in breast
cancer, we performed RNA-seq gene expression analysis on the basal breast cancer
progression model based on human MCF10A cells. Positional gene enrichment
identified the major histone gene cluster at chromosome 6p22 as one of the most
significantly upregulated (and not amplified) clusters of genes from the normal
like MCF10A to premalignant MCF10AT1 and metastatic MCF10CA1a cells. This cluster
is subdivided into three sub-clusters of histone genes that are organized into
hierarchical topologically associating domains (TADs). Interestingly, the sub
clusters of histone genes are located at TAD boundaries and interact more
frequently with each other than the regions in-between them, suggesting that the
histone sub-clusters form an active chromatin hub. The anchor sites of loops
within this hub are occupied by CTCF, a known chromatin organizer. These histone
genes are transcribed and processed at a specific sub-nuclear microenvironment
termed the major histone locus body (HLB). While the overall chromatin structure
of the major HLB is maintained across breast cancer progression, we detected
alterations in its structure that may relate to gene expression. Importantly,
breast tumor specimens also exhibit a coordinate pattern of upregulation across
the major histone gene cluster. Our results provide a novel insight into the
connection between the higher-order chromatin organization of the major HLB and
its regulation during breast cancer progression.
PMID- 28504307
TI - Family-based promotion of mental health in children affected by HIV: a pilot
randomized controlled trial.
AB - BACKGROUND: Children affected by HIV are at risk for poor mental health. We
conducted a pilot randomized controlled trial (RCT) of the Family Strengthening
Intervention (FSI-HIV), a family home-visiting intervention to promote mental
health and improve parent-child relationships in families with caregivers living
with HIV, hypothesizing that child and family outcomes would be superior to usual
care social work services. METHODS: Eighty two families (N = 170 children, 48.24%
female; N = 123 caregivers, 68.29% female) with at least one HIV-positive
caregiver (n = 103, 83.74%) and school-aged child (ages 7-17) (HIV+ n = 21,
12.35%) were randomized to receive FSI-HIV or treatment-as-usual (TAU). Local
research assistants blind to treatment conducted assessments of child mental
health, parenting practices, and family functioning at baseline, post
intervention, and 3-month follow-up. Multilevel modeling assessed effects of FSI
HIV on outcomes across three time points. TRIAL REGISTRATION: NCT01509573, 'Pilot
Feasibility Trial of the Family Strengthening Intervention in Rwanda (FSI-HIV
R).'
https://clinicaltrials.gov/ct2/show/;NCT01509573?term=Pilot+Feasibility+Trial+of+
he+Family+Strengthening+Intervention+in+Rwanda+%28FSI-HIV-R%29&rank=1. RESULTS:
At 3-month follow-up, children in FSI-HIV showed fewer symptoms of depression
compared to TAU by both self-report (beta = -.246; p = .009) and parent report
(beta = -.174; p = .035) but there were no significant differences by group on
conduct problems, functional impairment, family connectedness, or parenting.
CONCLUSIONS: Family-based prevention has promise for reducing depression symptoms
in children affected by HIV. Future trials should examine the effects of FSI-HIV
over time in trials powered to examine treatment mediators.
PMID- 28504309
TI - Deletion of the short N-terminal extension in OCP reveals the main site for FRP
binding.
AB - The orange carotenoid protein (OCP) plays a key role in cyanobacterial
photoprotection. Photoconversion entails structural rearrangements in OCP that
are required for its binding to phycobilisome, thereby inducing excitation energy
dissipation. Detachment of OCP from phycobilisome requires the fluorescence
recovery protein (FRP). It is considered that OCP interacts with FRP only in the
photoactivated state; however, the binding site for FRP is currently unknown. As
an important stabilizing element in orange OCP, the short alphaA-helix within the
N-terminal extension (NTE) binds to the C-terminal domain (CTD), but unfolds upon
photoactivation and interferes with phycobilisome binding. Here, we demonstrate
that the NTE shares specific structural and functional similarities with FRP and
discover the main site of OCP-FRP interactions in the OCP-CTD.
PMID- 28504308
TI - Brainstem as a developmental gateway to social attention.
AB - BACKGROUND: Evolution preserves social attention due to its key role in
supporting survival. Humans are attracted to social cues from infancy, but the
neurobiological mechanisms for the development of social attention are unknown.
An evolutionary-based, vertical-hierarchical theoretical model of self-regulation
suggests that neonatal brainstem inputs are key for the development of well
regulated social attention. METHODS: Neonates born preterm (N = 44, GA 34 w.)
were recruited and diagnosed at birth as a function of their auditory brainstem
evoked responses (ABR). Participants enrolled in a prospective 8-year-long,
double-blind, follow-up study comparing participants with brainstem dysfunctions
and well-matched controls. Groups had comparable fetal, neonatal, and familial
characteristics. Methods incorporated EEG power analysis and gaze tracking during
the Attention Network Test (ANT, four cue types, and two targets) and a Triadic
Gaze Engagement task (TGE, three social cue levels). RESULTS: Results showed that
neonatal brainstem compromise is related to long-term changes in Alpha- and Theta
band power asymmetries (p < .034, p < .016, respectively), suggesting suppressed
bottom-up input needed to alert social attention. Gaze tracking indicated
dysregulated arousal-modulated attention (p < .004) and difficulty in gaze
engagement to socially neutral compared to nonsocial cues (p < .012).
CONCLUSIONS: Integrating models of Autism and cross-species data with current
long-term follow-up of infants with discrete neonatal brainstem dysfunction
suggests neonatal brainstem input as a gateway for bottom-up regulation of social
attention.
PMID- 28504311
TI - Ultrasound-Guided Injection of the Temporalis Tendon: A Novel Technique.
AB - A novel technique, ultrasound-guided injection of the temporalis tendon in
adults, is described. Ultrasound-guided injection of the temporalis tendon is
based on visualization of the temporalis muscle, temporalis tendon, and coronoid
process. A practical step-by-step guide to doing the procedure is given. This
technique is effective and reproducible. Two patients successfully treated with
this technique will be briefly discussed. The anatomic location and size of the
temporalis tendon make it mandatory to use ultrasound to ensure precision.
PMID- 28504310
TI - Aerobic capacity mediates susceptibility for the transition from steatosis to
steatohepatitis.
AB - KEY POINTS: Low intrinsic aerobic capacity is associated with increased all-cause
and liver-related mortality in humans. Low intrinsic aerobic capacity in the low
capacity runner (LCR) rat increases susceptibility to acute and chronic high
fat/high-sucrose diet-induced steatosis, without observed increases in liver
inflammation. Addition of excess cholesterol to a high-fat/high-sucrose diet
produced greater steatosis in LCR and high capacity runner (HCR) rats. However,
the LCR rat demonstrated greater susceptibility to increased liver inflammatory
and apoptotic markers compared to the HCR rat. The progressive non-alcoholic
fatty liver disease observed in the LCR rats following western diet feeding was
associated with further declines in liver fatty acid oxidation and mitochondrial
respiratory capacity compared to HCR rats. ABSTRACT: Low aerobic capacity
increases risk for non-alcoholic fatty liver disease and liver-related disease
mortality, but mechanisms mediating these effects remain unknown. We recently
reported that rats bred for low aerobic capacity (low capacity runner; LCR)
displayed susceptibility to high fat diet-induced steatosis in association with
reduced hepatic mitochondrial fatty acid oxidation (FAO) and respiratory capacity
compared to high aerobic capacity (high capacity runner; HCR) rats. Here we
tested the impact of aerobic capacity on susceptibility for progressive liver
disease following a 16-week 'western diet' (WD) high in fat (45% kcal),
cholesterol (1% w/w) and sucrose (15% kcal). Unlike previously with a diet high
in fat and sucrose alone, the inclusion of cholesterol in the WD induced
hepatomegaly and steatosis in both HCR and LCR rats, while producing greater
cholesterol ester accumulation in LCR compared to HCR rats. Importantly, WD-fed
low-fitness LCR rats displayed greater inflammatory cell infiltration, serum
alanine transaminase, expression of hepatic inflammatory markers (F4/80, MCP-1,
TLR4, TLR2 and IL-1beta) and effector caspase (caspase 3 and 7) activation
compared to HCR rats. Further, LCR rats had greater WD-induced decreases in
complete FAO and mitochondrial respiratory capacity. Intrinsic aerobic capacity
had no impact on WD-induced hepatic steatosis; however, rats bred for low aerobic
capacity developed greater hepatic inflammation, which was associated with
reduced hepatic mitochondrial FAO and respiratory capacity and increased
accumulation of cholesterol esters. These results confirm epidemiological reports
that aerobic capacity impacts progression of liver disease and suggest that these
effects are mediated through alterations in hepatic mitochondrial function.
PMID- 28504312
TI - G-POEM with antro-pyloromyotomy for the treatment of refractory gastroparesis:
mid-term follow-up and factors predicting outcome.
AB - BACKGROUND: Gastric peroral endoscopic pyloromyotomy (G-POEM) was introduced for
treating refractory gastroparesis. AIM: To present a series of patients focussed
on clinical mid-term efficacy and predictive outcomes factors. METHODS: This was
a single centre study of 29 patients operated on between January 2014 and April
2016, with disturbed gastric emptying scintigraphy (GES) and/or elevated
Gastroparesis Cardinal Symptoms Index (GCSI). The procedures were performed as
previously described. The primary endpoint was the efficacy at 3 and 6 months,
based on GCSI and symptoms. The secondary endpoints were GES evolution, procedure
reproducibility and safety, and identification of predictive factors for success.
RESULTS: There were 10 men, 19 women (mean age 52.8+/-18). The technical success
rate was 100% (average 47 minutes). There were two complications managed
conservatively: one bleeding and one abscess. The median follow-up was 10+/-6.4
months. The clinical success rate was 79% at 3 months, 69% at 6 months, with a
significant decrease in the mean GCSI compared to pre-operatively (3.3+/-0.9 vs
1+/-1.2 and 1.1+/-0.9 respectively). The GES (n=23) normalised in 70% of cases,
with a significant improvement of the mean half emptying time and retention at 2
hours, and a discordance in 21% of the cases. In univariate analysis, diabetes
and female gender were significantly associated with risk of failure, but not
confirmed in multivariate analysis. CONCLUSIONS: The mid-term efficacy of G-POEM
reaches 70% at 6 months. The procedure remains reproducible and safe. Diabetes
and female gender were predictive of failure.
PMID- 28504313
TI - Ultrasound-Guided Fine-Needle Aspiration in the Neck Region Using an Optical See
Through Head-Mounted Display: A Randomized Controlled Trial.
AB - OBJECTIVES: The purpose of this study was to examine the feasibility of an
optical see-through head-mounted display (OST-HMD) to improve ergonomics during
ultrasound-guided fine-needle aspiration (FNA) in the neck region. METHODS: This
randomized controlled study compared an OST-HMD with a normal ultrasound monitor
during an ultrasound-guided FNA in the neck region. Patients with a neck tumor
were recruited and randomized into one of two groups. Two practitioners performed
ultrasound-guided FNA with or without the HMD, as indicated. An independent
researcher measured the procedure time, the number and time of head movements, as
well as the number of needle redirections. In addition, practitioners completed
questionnaires after performing the FNA on each patient. RESULTS: In 93% of the
sessions with the OST-HMD, practitioners performed ultrasound-guided FNA without
turning the patients' heads. There was no difference in procedural time and
number of needle redirections between the two groups. Results from the
questionnaire revealed not only good wearability and low fatigue, but also the
practitioners' preference for the HMD. CONCLUSIONS: The OST-HMD improved the
practitioners' ergonomics and can be adopted for performing ultrasound-guided
interventional procedures in clinical settings.
PMID- 28504314
TI - Next step in antibiotic stewardship: Pharmacist-provided penicillin allergy
testing.
AB - WHAT IS KNOWN: Penicillin allergy limits therapeutic options for patients but
often disappears over time, leaving patients erroneously labelled allergic and
leading to the utilization of broad-spectrum and more expensive antibiotics.
Penicillin allergy can be effectively assessed via skin testing. OBJECTIVE: To
improve patient access to penicillin allergy testing by implementing a pharmacist
provided service in a hospital setting. COMMENT: Beta-lactams remain a mainstream
therapy for many infections due to their effectiveness, low side effects and
affordability. Typically, patient access to penicillin allergy testing is limited
by the availability of allergy specialists, who traditionally perform such
testing. A pharmacist-provided penicillin allergy testing service was implemented
at our hospital in 2015 and became a powerful antibiotic stewardship tool.
Removing penicillin allergy from patient profiles significantly expanded
therapeutic options, expedited discharges and reduced costs of care. WHAT IS NEW:
Pharmacists can expand patient access to penicillin allergy testing. CONCLUSION:
Pharmacist-provided penicillin allergy testing permitted optimized antibiotic
treatment and expedited discharges.
PMID- 28504315
TI - Media Reporting on Suicide: Evaluating the Effects of Including Preventative
Resources and Psychoeducational Information on Suicide Risk, Attitudes,
Knowledge, and Help-Seeking Behaviors.
AB - We evaluated the effects of exposure to a suicide news article on a variety of
outcome variables and whether adhering to one specific media guideline (i.e.,
including psychoeducational information and preventative resources) buffered any
of the negative effects of exposure. Participants were randomly assigned to read
one of three articles and then asked to complete a battery of self-report
questionnaires. Overall, we found no effect of exposure to a suicide news
article, regardless of the inclusion of resources and information, with a few
minor exceptions. Although researchers have demonstrated the effectiveness of
media guidelines in the aggregate at reducing imitative suicidal behavior, it
remains unclear which guidelines in particular are responsible for this effect.
PMID- 28504316
TI - Rational design of a pH-insensitive cyan fluorescent protein CyPet2 based on the
CyPet crystal structure.
AB - The emission spectrum of widely used CyPet is pH-sensitive. In order to
synthesize a pH-insensitive cyan fluorescent protein by rational design, we
solved the crystal structures of CyPet under different pH conditions. The indole
group of the CyPet chromophore adopts a cis-coplanar conformation in acidic and
neutral conditions, while it converts to trans-coplanar under basic conditions.
His148 and Glu222 play a vital role in this isomerization. The pH-sensitive
chromophore isomerization and change in the emission spectrum can be explained by
the coexistence of several different fluorescent states. We trap the chromophore
in the trans conformation by A167I mutation (CyPet2), which also prevents the
multiconformation of the seventh beta-strand. CyPet2 exhibits an unchanged
emission spectral shape as a function of pH.
PMID- 28504317
TI - Adrenal cortex reactivity in dairy cows differs between lactational stages and
between different feeding levels.
AB - Changes in ACTH challenge test characteristics in dairy cows changing their
physiological status at different lactational stages and different feeding levels
were not investigated in terms of repeatability yet. In 23 multiparous Holstein
cows (10 cows fed a sole fresh herbage diet without concentrate, 13 cows fed with
concentrate), three ACTH challenge tests were performed: once during pregnancy
shortly prior to drying off (T1), and in week 3 (T2) and 8 (T3) after
parturition. Test characteristics were correlated to performance and metabolic
parameters: DMI, BW, energy balance (EB), plasma concentrations of free fatty
acids (NEFA) and beta-hydroxybutyrate (BHB). Basal plasma cortisol concentrations
were higher at T1 compared with T2 and T3 (p < .05). The adrenal cortex
sensitivity (expressed as total AUC (AUCt ) of cortisol response after ACTH
application) was lowest at T2 compared with T1 and T3 (p < .05). Ranking of the
individual animals' responses was not repeatable between time points of the ACTH
tests. Enhancing the energy deficiency during early lactation by omission of
concentrate did not affect baseline cortisol concentrations in plasma, but
decreased peak height at T2 (p < .05). Baseline plasma cortisol concentrations
were positively correlated with cortisol peak values after ACTH application,
previous lactation performance, milk yield and BW (p < .05). The AUCt was
positively correlated with baseline cortisol concentrations, EB and DMI. Cortisol
release after ACTH injection was lower in animals with high plasma concentrations
of NEFA, BHB and with higher contents of fat and free fatty acids in milk (p <
.05). Cortisol peak height after ACTH administration was higher in cows with a
more positive EB, higher DMI and lower plasma concentrations of NEFA and BHB. In
summary, cortisol responses to ACTH challenges in this study were not repeatable
in dairy cows changing their physiological status.
PMID- 28504318
TI - Antifungal prophylaxis in newly diagnosed AML patients-Adherence to guidelines
and feasibility in a real life setting.
AB - Antifungal posaconazole prophylaxis for AML patients receiving induction
chemotherapy has been routine at our centre since 2009. This retrospective study
examined the feasibility and practicability of our prophylaxis guidelines in
clinical practice. Data sets of 90 patients undergoing induction-chemotherapy for
AML between 2011 and 2014 were evaluated regarding adherence to local guidelines
for the administration of antifungal prophylaxis with posaconazole. 75.5% of the
90 patients received posaconazole prophylaxis. All but eight patients received
the recommended dosage. A total of 77.95% on prophylaxis had serum galactomannan
measured twice weekly. Contradicting our guidelines, 89.70% of patients received
concomitant therapy with PPI. Overall, 16.17% of patients had prophylaxis
discontinued and started empirical antifungal treatment in the absence of
diagnostic criteria for IFI. The breakthrough IFI rate was 36.76% (proven,
probable and possible) with 7.35% of infections being classified as proven or
probable. Although limited by a small sample size, our study demonstrates the
feasibility of local guidelines in a real life setting and outlines areas for
improvement in both guidelines and clinical practice. We also highlight the
importance of ensuring awareness of guidelines and raise questions about a
uniform approach to antifungal prophylaxis in AML patients.
PMID- 28504319
TI - Biological response of commercially available different tricalcium silicate-based
cements and pozzolan cement.
AB - This study evaluated four root repair materials for cytotoxicity and cell
attachment in vitro. Cell viability was determined at 24 hr, 3 days and 7 days by
using a 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide
(XTT) assay with material extracts. Cell adhesion was examined with a scanning
electron microscope on the surface of materials at 24 and 48 hr. Angelus MTA
displayed the lowest cell viabilities at all-day incubations. Endocem had high
biocompatibility on the first day. After culturing for 3 days and 7 days, the
cell viabilities of Biodentine, Endocem and MM-MTA had similar results, and their
cell viability was significantly higher than that of Angelus. No definite
relation was found between the incubation time and the relative cell viability in
any group. In scanning electron micrographs, the cells were attached to the
material surface for all materials, although the cells in the Biodentine group
were attached better than the other groups on the second day. Cell viability and
cell attachment was lower in the Angelus group. Endocem, Biodentine and MM-MTA
were similar in biocompatibility and cytotoxicity.
PMID- 28504320
TI - Photosensitization Priming of Tumor Microenvironments Improves Delivery of
Nanotherapeutics via Neutrophil Infiltration.
AB - Remodeling of tumor microenvironments enables enhanced delivery of nanoparticles
(NPs). This study shows that direct priming of a tumor tissue using
photosensitization rapidly activates neutrophil infiltration that mediates
delivery of nanotherapeutics into the tumor. A drug delivery platform is
comprised of NPs coated with anti-CD11b antibodies (Abs) that target activated
neutrophils. Intravital microscopy demonstrates that the movement of anti-CD11b
Abs-decorated NPs (NPs-CD11b) into the tumor is mediated by neutrophil
infiltration induced by photosensitization (PS) because the systemic depletion of
neutrophils completely abolishes the nanoparticle tumor deposition. The
neutrophil uptake of NPs does not alter neutrophil activation and transmigration.
For cancer therapy in mice, tumor PS and photothermal therapy of anti-CD11b Abs
linked gold nanorods (GNRs-CD11b) are combined to treat the carcinoma tumor. The
result indicates that neutrophil tumor infiltration enhances nanoparticle cancer
therapy. The findings reveal that promoting tumor infiltration of neutrophils by
manipulating tumor microenvironments could be a novel strategy to actively
deliver nanotherapeutics in cancer therapies.
PMID- 28504321
TI - Hemodynamic responses and plasma phenylephrine concentrations associated with
intranasal phenylephrine in children.
AB - INTRODUCTION: Intranasal phenylephrine, an alpha-1 adrenergic agonist, causes
vasoconstriction of the nasal mucosa and is used to reduce bleeding associated
with nasotracheal intubation or endoscopic sinus surgery. The purpose of this
study was to describe the hemodynamic effects associated with plasma
phenylephrine concentrations following topical intranasal administration of 0.25%
and 0.5% phenylephrine in children. METHODS: After Institutional Review Board and
parental approval, 77 children between the ages of 2 and 12 years were studied in
a prospective, double-blind manner and randomized into three groups. Group 1
received intranasal saline, while groups 2 and 3 received 0.1 mL/kg of 0.25% or
0.5% phenylephrine, respectively. All received the same anesthetic of halothane,
N2 O, O2 , and vecuronium. After inhalation induction, endtidal halothane and
PaCO2 were maintained at 1.5% and 35 mm Hg, respectively. Heart rate and rhythm,
systolic, diastolic, and mean, noninvasive arterial blood pressures were recorded
and venous blood was obtained for measurement of plasma phenylephrine
concentration by high-performance liquid chromatography at baseline and at 2, 5,
10, and 20 minutes following intranasal spray application of the study drug.
Nasotracheal intubation was performed immediately following the 5-minute
measurements, and the presence of bleeding was assessed. Hemodynamic data were
compared by analysis of variance for repeated measures. Bleeding and arrhythmia
incidence among groups were analyzed using chi-squared tests. Phenylephrine
levels were correlated with hemodynamic values via regression analysis. RESULTS:
Fifty-two patients received intranasal phenylephrine. Increases in blood pressure
correlated with increasing plasma phenylephrine concentration. Systolic blood
pressure increased 8%, and mean blood pressure increased 14%, which were
statistically significant but clinically insignificant. Heart rate did not
change, and the incidence of arrhythmia was low and similar among groups.
Bleeding following nasotracheal intubation was less frequent in Group 3 (11/27
subjects) than in Group 1 (17/25). Peak plasma phenylephrine concentrations were
observed by 14+/-7 minutes following intranasal administration, and were highly
variable among individuals (37.8+/-39.7 and 49.6+/-93.9 ng/mL [mean+/-SD] in
Groups 2 and 3). DISCUSSION: Administration of intranasal phenylephrine, 0.25%
and 0.50%, results in rapid but highly variable systemic absorption that is
associated with mild increases of blood pressure that are clinically
insignificant. Bleeding associated with nasotracheal intubation was less
following administration of 0.5% intranasal phenylephrine than following
intranasal saline.
PMID- 28504322
TI - Racial differences in the pain management of children recovering from anesthesia.
AB - BACKGROUND: When pain management has been studied in settings such as pediatric
emergency departments, racial disparities have been clearly identified. To our
knowledge, this has not been studied in the pediatric perioperative setting. We
sought to determine whether there are differences based on race in the
administration of analgesia to children suffering from pain in the postanesthesia
care unit. METHODS: This is a prospective, observational, study of 771 children
aged 4-17 years who underwent elective outpatient surgery. Racial differences in
probability of receiving analgesia for pain in the recovery room were assessed
using bivariable and multivariable logistic regression analyses. RESULTS: A total
of 294 children (38.2%) received at least one class of analgesia (opioid or
nonopioid); while 210 (27.2%) received intravenous (i.v.) opioid analgesia in the
recovery room. Overall postanesthesia care unit analgesia utilization was similar
between white and minority children (white children 36.8% vs minority children
43.4%, OR 1.3; 95% CI=0.92-1.89; P=.134). We found no significant difference by
racial/ethnic group in the likelihood of a child receiving i.v. opioid for severe
postoperative pain (white children 76.0% vs 85.7%, OR 1.89; 95% CI=0.37-9.67;
P=.437). However, minority children were more likely to receive i.v. opioid
analgesia than their white peers (white children 24.5% vs minority children
34.2%, OR 1.5; 95% CI=1.04-2.2; P=.03). On multivariable analysis, minority
children had a 63% higher adjusted odds of receiving i.v. opioids in the recovery
room (OR=1.63; 95% CI, 1.05-2.62; P=.03). CONCLUSIONS: Receipt of analgesia for
acute postoperative pain was not significantly associated with a child's race.
Minority children were more likely to receive i.v. opioids for the management of
mild pain.
PMID- 28504323
TI - The Systemic Interaction of Attachment on Psychophysiological Arousal in Couple
Conflict.
AB - Attachment in adult romantic relationships has long been linked to conflict
styles. Psychophysiological measures have provided additional insight into this
association by accessing less conscious and controlled responses to conflict. The
aim of this study was to explore the relationship between attachment anxiety,
attachment avoidance, and the interaction between attachment styles on skin
conductance responses during conflict and recovery from conflict. Using dyadic
analysis of 50 heterosexual couples, we found evidence of a systemic effect of
attachment, where psychophysiological arousal increased when one partner had
higher levels of attachment anxiety and the other partner had higher levels of
attachment avoidance. Attachment avoidance was also negatively associated with
increased levels of arousal. Relationship and clinical implications of these
findings are discussed.
PMID- 28504324
TI - Electromagnetic Fields, Pulsed Radiofrequency Radiation, and Epigenetics: How
Wireless Technologies May Affect Childhood Development.
AB - Mobile phones and other wireless devices that produce electromagnetic fields
(EMF) and pulsed radiofrequency radiation (RFR) are widely documented to cause
potentially harmful health impacts that can be detrimental to young people. New
epigenetic studies are profiled in this review to account for some
neurodevelopmental and neurobehavioral changes due to exposure to wireless
technologies. Symptoms of retarded memory, learning, cognition, attention, and
behavioral problems have been reported in numerous studies and are similarly
manifested in autism and attention deficit hyperactivity disorders, as a result
of EMF and RFR exposures where both epigenetic drivers and genetic (DNA) damage
are likely contributors. Technology benefits can be realized by adopting wired
devices for education to avoid health risk and promote academic achievement.
PMID- 28504325
TI - Therapeutic ultrasound for venous leg ulcers.
AB - BACKGROUND: Venous leg ulcers are a type of chronic, recurring, complex wound
that is more common in people aged over 65 years. Venous ulcers pose a
significant burden to patients and healthcare systems. While compression therapy
(such as bandages or stockings) is an effective first-line treatment, ultrasound
may have a role to play in healing venous ulcers. OBJECTIVES: To determine
whether venous leg ulcers treated with ultrasound heal more quickly than those
not treated with ultrasound. SEARCH METHODS: We searched the Cochrane Wounds
Specialised Register (searched 19 September 2016); the Cochrane Central Register
of Controlled Trials (CENTRAL; the Cochrane Library 2016, Issue 8); Ovid MEDLINE
(including In-Process & Other Non-Indexed Citations, MEDLINE Daily and Epub Ahead
of Print) (1946 to 19 September 2016); Ovid Embase (1974 to 19 September 2016);
and EBSCO CINAHL Plus (1937 to 19 September 2016). We also searched three
clinical trials registries and the references of included studies and relevant
systematic reviews. There were no restrictions based on language, date of
publication or study setting. SELECTION CRITERIA: Randomised controlled trials
(RCTs) that compared ultrasound with no ultrasound. Eligible non-ultrasound
comparator treatments included usual care, sham ultrasound and alternative leg
ulcer treatments. DATA COLLECTION AND ANALYSIS: Two authors independently
assessed the search results and selected eligible studies. Details from included
studies were summarised using a data extraction sheet, and double-checked. We
attempted to contact trial authors for missing data. MAIN RESULTS: Eleven trials
are included in this update; 10 of these we judged to be at an unclear or high
risk of bias. The trials were clinically heterogeneous with differences in
duration of follow-up, and ultrasound regimens. Nine trials evaluated high
frequency ultrasound; seven studies provided data for ulcers healed and two
provided data on change in ulcer size only. Two trials evaluated low frequency
ultrasound and both reported ulcers healed data.It is uncertain whether high
frequency ultrasound affects the proportion of ulcers healed compared with no
ultrasound at any of the time points evaluated: at seven to eight weeks (RR 1.21,
95% CI 0.86 to 1.71; 6 trials, 678 participants; low quality evidence -
downgraded once for risk of bias and once for imprecision); at 12 weeks (RR 1.26,
95% CI 0.92 to 1.73; 3 trials, 489 participants; moderate quality evidence -
downgraded once for imprecision); and at 12 months (RR 0.93, 95% CI 0.73 to 1.18;
1 trial, 337 participants; low quality evidence - downgraded once for unclear
risk of bias and once for imprecision).One trial (92 participants) reported that
a greater percentage reduction in ulcer area was achieved at four weeks with high
frequency ultrasound, while another (73 participants) reported no clear
difference in change in ulcer size at seven weeks. We downgraded the level of
this evidence to very low, mainly for risk of bias (typically lack of blinded
outcome assessment and attrition) and imprecision.Data from one trial (337
participants) suggest that high frequency ultrasound may increase the risk of non
serious adverse events (RR 1.29, 95% CI 1.02 to 1.64; moderate quality evidence -
downgraded once for imprecision) and serious adverse events (RR 1.21, 95% CI 0.78
to 1.89; moderate quality evidence downgraded once for imprecision).It is
uncertain whether low frequency ultrasound affects venous ulcer healing at eight
and 12 weeks (RR 3.91, 95% CI 0.47 to 32.85; 2 trials, 61 participants; very low
quality evidence (downgraded for risk of bias and imprecision)).High-frequency
ultrasound probably makes little or no difference to quality of life (moderate
quality evidence, downgraded for imprecision). The outcomes of adverse effects,
quality of life and cost were not reported for low-frequency ultrasound
treatment. AUTHORS' CONCLUSIONS: It is uncertain whether therapeutic ultrasound
(either high or low frequency) improves the healing of venous leg ulcers. We
rated most of the evidence as low or very low quality due to risk of bias and
imprecision.
PMID- 28504328
TI - Response to Miller and Johnston.
PMID- 28504326
TI - Preoperative colonization in pediatric cardiac surgery and its impact on
postoperative infections.
AB - BACKGROUND: Patients with congenital heart defects are frequently hospitalized
before surgery. This exposes them to a high risk for pathogen colonization. There
are limited data on colonization prevalence in the pediatric cardiac population,
and limited data concerning its potential role in the risk of developing
infections after cardiac surgery. AIM: This study aimed to verify the impact of
preoperative colonization on postoperative infections in a population of
pediatric cardiac surgery patients coming from Italy and developing countries.
METHODS: This was a retrospective study conducted in all the patients aged <=18
years who underwent pediatric open-heart surgery in the year 2015. Clinical data
were retrieved from the institutional database for cardiac surgery patients. Data
on swab cultures were retrieved from the laboratory database. Swab colonization
was tested for association with infection and other outcomes. RESULTS: Among 169
children who performed the screening for pathogen colonization, 50% had at least
one positive swab. Italian patients were (P=.001) less likely to be colonized
with respect to foreign patients (relative risk 0.17, 95% CI 0.09-0.35).
Postoperative infections in colonized patients occurred at a similar rate as in
noncolonized patients (relative risk 1.24, 95% CI 0.64-2.39; P=.532). Colonized
patients had a preoperative stay (P=.021) longer than noncolonized patients (mean
difference 2 days, 95% CI 0.3-3.8 days). CONCLUSION: The results of our study
suggest that the impact of preoperative colonization on outcome and postoperative
infections may be negligible; larger series are required to clearly define this
issue.
PMID- 28504329
TI - Rediscovering the ritual technology of the placebo effect in analytical
psychology.
AB - Technology, viewed more generally, is a collection of skills and methods that are
used to accomplish an objective of some kind. Modernity has produced many kinds
of ever-expanding new technologies, but it is also evident that technologies can
be lost or fall out of use. A cross-cultural survey of ritual reveals a rather
startling observation: that while developed nations often exceed other cultures
in terms of material technology, they often pale by comparison in their use of
ritual technology. In this essay we will see how ritual is a powerful sort of
technology that developed nations have mostly allowed to drift out of regular,
vigorous use, despite its numerous psychological and biological effects. This
tendency has left one of the rituals we still have - psychotherapy itself - to be
bereft of some of the typical tools for concretizing the symbolic in recurrent
patterns around the world. Jung himself could be accused of being somewhat anti
ritual himself, enmeshed as he was in the post-Protestant, post-Enlightenment
cultural environment that defines the West in many ways. But these under-utilized
elements of ritual technology may be a natural fit for Jungian therapy due to its
use of symbols.
PMID- 28504327
TI - Preferences for prenatal diagnosis of sickle-cell disorder: A discrete choice
experiment comparing potential service users and health-care providers.
AB - BACKGROUND: Non-invasive prenatal diagnosis (NIPD) for sickle-cell disorder (SCD)
is moving closer to implementation and studies considering stakeholder
preferences are required to underpin strategies for offering NIPD in clinical
practice. OBJECTIVE: Determine service user and provider preferences for key
attributes of prenatal diagnostic tests for SCD and examine views on NIPD.
METHOD: A questionnaire that includes a discrete choice experiment was used to
determine the preferences of service users and providers for prenatal tests that
varied across three attributes: accuracy, time of test and risk of miscarriage.
RESULTS: Adults who were carriers of SCD or affected with the condition (N=67)
were recruited from haemoglobinopathy clinics at two maternity units. Health
professionals, predominately midwives, who offer antenatal care (N=62) were
recruited from one maternity unit. No miscarriage risk was a key driver of
decision making for both service users and providers. Service providers placed
greater emphasis on accuracy than service users. Current uptake of invasive tests
was 63%, whilst predicted uptake of NIPD was 93.8%. Many service users (55.4%)
and providers (52.5%) think pressure to have prenatal testing will increase when
NIPD for SCD becomes available. CONCLUSIONS: There are clear differences between
service users and health professionals' preferences for prenatal tests for sickle
cell disorder. The safety of NIPD is welcomed by parents and uptake is likely to
be high. To promote informed choice, pretest counselling should be balanced and
not exclusively focused on test safety. Counselling strategies that are sensitive
to feelings of pressure to test will be essential.
PMID- 28504330
TI - Analytical practice: do the new technologies have an impact?
AB - Through commentary on four clinical vignettes, this article focuses on the
anthropological transformations taking place in contemporary society, underlining
their differences from the anthropologies of reference of the founding fathers of
psychoanalysis. Hybridization between man and machine and the speeding up and
alteration of communications which the new technologies promote are now crucial
issues facing psychoanalysis. Social media and a 24/7 internet connection have
produced deep changes in the way people live and perceive relationships.
Analytical practice is not exempt from such issues, which can be particularly
insidious, often subtle and difficult to recognize, or even underestimated or
ignored by psychoanalysts outright, in order to preserve the illusion of a
complete understanding of what unfolds in the analytical space. The authors
suggest that such transformations, by (partially) rendering inadequate the
theoretical and technical corpus on which the various depth psychologies are
founded, require personal engagement on the part of psychoanalysts in the search
for new strategies to treat their patients, with the consequent abandonment of
the 'certainties' offered by sclerotic models of clinical procedure.
PMID- 28504331
TI - A response to Steve Myers: The transcendent function is different in kind.
PMID- 28504332
TI - Guest editorial: Jung and technology.
PMID- 28504334
TI - Advances in functional brain imaging technology and developmental neuro
psychology: their applications in the Jungian analytic domain.
AB - Analytical psychology shares with many other psychotherapies the important task
of repairing the consequences of developmental trauma. The majority of analytic
patients come from compromised early developmental backgrounds: they may have
experienced neglect, abuse, or failures of empathic resonance from their carers.
Functional brain imagery techniques including Quantitative Electroencephalogram
(QEEG), and functional Magnetic Resonance Imagery (fMRI), allow us to track
mental processes in ways beyond verbal reportage and introspection. This
independent perspective is useful for developing new psychodynamic hypotheses,
testing current ones, providing diagnostic markers, and monitoring treatment
progress. Jung, with the Word Association Test, grasped these principles 100
years ago. Brain imaging techniques have contributed to powerful recent advances
in our understanding of neurodevelopmental processes in the first three years of
life. If adequate nurturance is compromised, a range of difficulties may emerge.
This has important implications for how we understand and treat our psychotherapy
clients. The paper provides an overview of functional brain imaging and advances
in developmental neuropsychology, and looks at applications of some of these
findings (including neurofeedback) in the Jungian psychotherapy domain.
PMID- 28504335
TI - Tele-analysis: the use of media technology in psychotherapy and its impact on the
therapeutic relationship.
AB - A growing number of approaches in psychotherapy make use of internet- and other
media-based interactions. This paper discusses the impact on the therapist-client
relationship of using media technology and gives an overview of the current state
of the debate. It is suggested that the technical conditions of internet-based
interactions produce new forms of social relationships that differ significantly
from face-to-face-interactions and that unconscious, nonverbal cues get lost.
Research on the therapeutic interaction making use of 'discourse linguistic'
methods is presented. The loss of nonverbal cues has implications for
psychotherapy in general and especially for the treatment of patients who have
difficulties relying on a secure therapeutic relationship. Emotional security in
interactional relationships is transmitted to a much greater extent by nonverbal
cues than by verbal content; psychoanalytic methods are specialized to refer to
this level of interaction. Two alternative scenarios are discussed based on the
psychoanalytic theories of Winnicott and Lacan: the risk of an illusionary,
idealized image of the other and the possibility that cyberspace can be used for
psychological development as a transitional space.
PMID- 28504337
TI - Archaic man meets a marvellous automaton: posthumanism, social robots,
archetypes.
AB - Posthumanism is associated with critical explorations of how new technologies are
rewriting our understanding of what it means to be human and how they might alter
human existence itself. Intersections with analytical psychology vary depending
on which technologies are held in focus. Social robotics promises to populate
everyday settings with entities that have populated the imagination for
millennia. A legend of A Marvellous Automaton appears as early as 350 B.C. in a
book of Taoist teachings, and is joined by ancient and medieval legends of
manmade humanoids coming to life, as well as the familiar robots of modern
science fiction. However, while the robotics industry seems to be realizing an
archetypal fantasy, the technology creates new social realities that generate
distinctive issues of potential relevance for the theory and practice of
analytical psychology.
PMID- 28504338
TI - Plasmonic-Based Electrochemical Impedance Imaging of Electrical Activities in
Single Cells.
AB - Studying electrical activities in cells, such as action potential and its
propagation in neurons, requires a sensitive and non-invasive analytical tool
that can image local electrical signals with high spatial and temporal
resolutions. Here we report a plasmonic-based electrochemical impedance imaging
technique to study transient electrical activities in single cells. The technique
is based on the conversion of the electrical signal into a plasmonic signal,
which is imaged optically without labels. We demonstrate imaging of the fast
initiation and propagation of action potential within single neurons, and
validate the imaging technique with the traditional patch clamp technique. We
anticipate that the plasmonic imaging technique will contribute to the study of
electrical activities in various cellular processes.
PMID- 28504340
TI - A Single Spherical Assembly of Protein Amyloid Fibrils Formed by Laser Trapping.
AB - Protein amyloids have received much attention owing to their correlation with
serious diseases and to their promising mechanical and optical properties as
future materials. Amyloid formation has been conducted by tuning temperature and
chemical conditions, so that its nucleation and the following growth are analyzed
as ensemble dynamics. A single spherical assembly of amyloid fibrils of
cytochrome c domain-swapped dimer was successfully generated upon laser trapping.
The amyloid fibrillar structure was confirmed by fluorescence characterization
and electron microscopy. The prepared spheres were further manipulated
individually in solution to fabricate a three-dimensional microstructure and a
line pattern. Amyloid formation dynamics and amyloid-based microstructure
fabrication are demonstrated based on direct observation of a single spherical
assembly, which foresees a new approach in amyloid studies.
PMID- 28504339
TI - Mexneurin is a novel precursor of peptides in the central nervous system of
rodents.
AB - Endomorphins (EMs) have been proposed as the endogenous ligand agonists of the MU
opioid receptor; however, no propeptide precursor protein for EMs has been
identified. Here, to identify the presumed precursor of EMs, we designed an
immunoscreening assay using specific affinity-purified rabbit antisera raised
against synthetic EMs in a whole-mouse brain cDNA library. Following this
approach, we identify a DNA sequence encoding a protein precursor, which we name
proMexneurin, that contains three different peptide sequences: Mexneurin-1 (an EM
like peptide), Mexneurin-2, and Mexneurin-3, a peptide which appears to be
unrelated to EMs. RT-PCR analysis and in situ hybridization reveal a widespread
distribution of proMexneurin mRNA throughout the mouse brain. Both Mexneurin-1
and Mexneurin-3 peptides display biological activities in the mouse CNS.
PMID- 28504341
TI - Breathing circuit compliance and accuracy of displayed tidal volume during
pressure-controlled ventilation of infants: A quality improvement project.
AB - INTRODUCTION: Anesthesia machines have evolved to deliver desired tidal volumes
more accurately by measuring breathing circuit compliance during a preuse self
test and then incorporating the compliance value when calculating expired tidal
volume. The initial compliance value is utilized in tidal volume calculation
regardless of whether the actual compliance of the breathing circuit changes
during a case, as happens when corrugated circuit tubing is manually expanded
after the preuse self-test but before patient use. We noticed that the anesthesia
machine preuse self-test was usually performed on nonexpanded pediatric circuit
tubing, and then the breathing circuit was subsequently expanded for clinical
use. We aimed to demonstrate that performing the preuse self-test in that manner
could lead to incorrectly displayed tidal volume on the anesthesia machine
monitor. The goal of this quality improvement project was to change the usual
practice and improve the accuracy of displayed tidal volume in infants undergoing
general anesthesia. METHODS: There were four stages of the project: (i) gathering
baseline data about the performance of the preuse self-test and using infant and
adult test lungs to measure discrepancies of displayed tidal volumes when
breathing circuit compliance was changed after the initial preuse self-test; (ii)
gathering clinical data during pressure-controlled ventilation comparing
anesthesia machine displayed tidal volume with actual spirometry tidal volume in
patients less than 10 kg before (machine preuse self-test performed while the
breathing circuit was nonexpanded) and after an intervention (machine preuse self
test performed after the breathing circuit was fully expanded); (iii) performing
department-wide education to help implement practice change; (iv) gathering
postintervention data to determine the prevalence of proper machine preuse self
test. RESULTS: At constant pressure-controlled ventilation through fully expanded
circuit tubing, displayed tidal volume was 83% greater in the infant test lung
(mean+/-SD TV 15+/-5 vs 9+/-4 mL; mean [95% CI] difference=6.3 [5.6, 7.1] mL,
P<.0001) and 3% greater in the adult test lung (245+/-74 vs 241+/-72 mL;
difference=5 [1, 10] mL, P=.0905) when circuit compliance had been measured with
nonexpanded tubing compared to when circuit compliance was measured with fully
expanded tubing. The clinical data in infants demonstrated that displayed tidal
volume was 41% greater than actual tidal volume (difference of 10.4 [8.6, 12.2]
mL) when the circuit was expanded after the preuse self-test (preintervention)
and 7% greater (difference of 2.5 [0.7, 4.2] mL) in subjects when the circuit was
expanded prior to the preuse self-test (postintervention) (P<.0001). Clinical
practice was changed following an intervention of departmental education: the
preuse self-test was performed on expanded circuit tubing 11% of the time prior
to the intervention and 100% following the intervention. CONCLUSION: Performing a
preuse self-test on a nonexpanded pediatric circuit that is then expanded leads
to falsely elevated displayed tidal volume in infants less than 10 kg during
pressure-controlled ventilation. Overestimation of reported tidal volume can be
avoided by expanding the breathing circuit tubing to the length which will be
used during a case prior to performing the anesthesia machine preuse self-test.
After department-wide education and implementation, performing a correct preuse
self-test is now the standard practice in our cardiac operating rooms.
PMID- 28504342
TI - Sudden death in a pediatric heart transplant recipient with peripheral
eosinophilia and eosinophilic myocardial infiltrates.
AB - Eosinophilia has been rarely reported in pediatric heart transplant recipients
and has been suggested to play a role in graft rejection. We report a case of a
young female patient with peripheral blood eosinophilia who died suddenly 2 years
following ABO-incompatible heart transplantation. She was found at autopsy to
have myocardial infiltration of not only T-lymphocytes and macrophages expected
in acute cellular rejection but also of eosinophils, B-lymphocytes, and plasma
cells indicating myocarditis.
PMID- 28504343
TI - Gas Diffusion in the CNS.
AB - Gases have been long known to have essential physiological functions in the CNS
such as respiration or regulation of vascular tone. Since gases have been
classically considered to freely diffuse, research in gas biology has so far
focused on mechanisms of gas synthesis and gas reactivity, rather than gas
diffusion and transport. However, the discovery of gas pores during the last two
decades and the characterization of diverse diffusion patterns through different
membranes has raised the possibility that modulation of gas diffusion is also a
physiologically relevant parameter. Here we review the means of gas movement into
and within the brain through "free" diffusion and gas pores, notably aquaporins,
discussing the role that gas diffusion may play in the modulation of gas
function. We highlight how diffusion is relevant to neuronal signaling, volume
transmission, and cerebrovascular control in the case of NO, one of the most
extensively studied gases. We point out how facilitated transport can be
especially relevant for gases with low permeability in lipid membranes like NH3
and discuss the possible implications of NH3 -permeable channels in physiology
and hyperammonemic encephalopathy. We identify novel research questions about how
modulation of gas diffusion could intervene in CNS pathologies. This emerging
area of research can provide novel and interesting insights in the field of gas
biology.
PMID- 28504346
TI - Harvesting and blending options for lower alcohol wines: a sensory and chemical
investigation.
AB - BACKGROUND: Lower alcohol wines often have a poor reputation among consumers, in
part due to their unsatisfactory flavours such as reduced overall aroma intensity
or herbaceous characters. The aim of this study, performed on Verdelho and Petit
Verdot, was to quantify the effectiveness of a monovarietal blend in which wines
made from less ripe grapes were blended with an equivalent volume of a wine
vinified from riper fruit to produce wines with a lower alcohol content and
desirable ripe fruit flavours. RESULTS: Eleven and 13 attributes, for Verdelho
and Petit Verdot, respectively, were selected during sensory descriptive
analysis. Intensities of perceived 'acidity', 'sweetness' and 'alcohol'
attributes were significantly different (P <= 0.05) between the blend (8.8 +/-
0.1% v/v) and mature Verdelho (10.3 +/- 0.1% v/v) wines, while no significant
differences were found between the Petit Verdot blend (11.0 +/- 0.1% v/v) and
mature (12.6 +/- 0.2% v/v) treatments. Volatile composition of wines was assessed
using HS-SPME-GC-MS. Partial least square regression suggested relationships
between sensory descriptors and chemical attributes in the wines, as well as the
modifications of sensory and compositional profiles following blending.
CONCLUSIONS: The blending practice described allowed the production of wines with
lower alcohol content while retaining similar sensory profiles of the later
harvested, riper fruit wines. (c) 2017 Society of Chemical Industry.
PMID- 28504344
TI - Following Rapoport's Rule: the geographic range and genome size of bacterial taxa
decline at warmer latitudes.
AB - We sought to test whether stream bacterial communities conform to Rapoport's
Rule, a pattern commonly observed for plants and animals whereby taxa exhibit
decreased latitudinal range sizes closer to the equator. Using a DNA sequencing
approach, we explored the biogeography of biofilm bacterial communities in 204
streams across a ~1000 km latitudinal gradient. The range sizes of bacterial taxa
were strongly correlated with latitude, decreasing closer to the equator, which
coincided with a greater than fivefold increase in bacterial taxonomic richness.
The relative richness and range size of bacteria were associated with spatially
correlated variation in temperature and rainfall. These patterns were observed
despite enormous variability in catchment environmental characteristics. Similar
results were obtained when restricting the same analyses to native forest
catchments, thereby controlling for spatial biases in land use. We analysed
genomic data from ~500 taxa detected in this study, for which data were available
and found that bacterial communities at cooler latitudes also tended to possess
greater potential metabolic potential. Collectively, these data provide the first
evidence of latitudinal variation in the range size distributions of freshwater
bacteria, a trend which may be determined, in part, by a trade-off between
bacterial genome size and local variation in climatic conditions.
PMID- 28504347
TI - A rapid method to screen poisoning causative agents in an acute care hospital in
Japan.
AB - WHAT IS KNOWN AND OBJECTIVE: A simple, rapid analysis is required to
simultaneously analyse medicinal toxicants in emergency medical care. In this
regard, the analysis of blood samples by LC-MS/MS equipped with a spin column,
involving a rapid, simple pretreatment, has attracted attention. In this study,
sample pretreatment using a Monospin C18 column was performed to screen 11
medicinal toxicants in blood samples by LC-MS/MS. METHODS: Serum samples
supplemented with 11 medical toxicants-acetaminophen, salicylic acid, nitrazepam,
diphenhydramine, bromvalerylurea, phenobarbital, amitriptyline, risperidone,
fenitrothion, malathion and methomyl-were pretreated with the Monospin C18 column
according to Pretreatment I and Pretreatment II, followed by LC-MS/MS analysis.
RESULTS AND DISCUSSION: All toxicants were not detected by a single pretreatment
method but were detected by two pretreatment methods. According to Pretreatment
I, 10 medicinal toxicants-excluding salicylic acid-were detected. The recovery
rates of all medicinal toxicants, except acetaminophen and methomyl, were greater
than or equal to 80%. Salicylic acid was detected by Pretreatment II, with a
recovery rate of 57.1%. Although the coefficient of variation was less than that
reported in previous methods employing SPE, the recovery rates were better
possibly because of the simultaneous adsorption of water- and lipid-soluble
substances and evaporation by drying. WHAT IS NEW AND CONCLUSION: As LC-MS/MS
analysis using Monospin C18 can simultaneously and rapidly screen several
medicinal toxicants present in blood samples, it is expected to be highly
suitable for clinical settings.
PMID- 28504348
TI - Broad Spectrum Macromolecular Antimicrobials with Biofilm Disruption Capability
and In Vivo Efficacy.
AB - In this study, antimicrobial polymers are synthesized by the organocatalytic ring
opening polymerization of an eight-membered heterocyclic carbonate monomer that
is subsequently quaternized with methyl iodide. These polymers demonstrate
activity against clinically relevant Gram-positive Staphylococcus epidermidis and
Staphylococcus aureus, Gram-negative Escherichia coli and Pseudomonas aeruginosa,
and fungus Candida albicans with fast killing kinetics. Importantly, the polymer
efficiently inhibits biofilm growth and lyses existing biofilm, leading to a
reduction in biomass and cell viability. In addition, the macromolecular
antimicrobial is less likely to induce resistance as it acts via a membrane-lytic
mechanism. The polymer is not cytotoxic toward mammalian cells with LD50 of 99.0
+/- 11.6 mg kg-1 in mice through i.v. injection. In an S. aureus blood stream
infection mouse model, the polymer removes bacteria from the blood more rapidly
than the antibiotic Augmentin. At the effective dose, the polymer treatment does
not damage liver and kidney tissues or functions. In addition, blood electrolyte
balance remains unchanged after the treatment. The low cost of starting
materials, ease of synthesis, nontoxicity, broad spectrum activity with fast
killing kinetics, and in vivo antimicrobial activity make these macromolecular
antimicrobials ideal candidates for prevention of sepsis and treatment of
infections.
PMID- 28504349
TI - Polysome profiling of mAb producing CHO cell lines links translational control of
cell proliferation and recombinant mRNA loading onto ribosomes with global and
recombinant protein synthesis.
AB - mRNA translation is a key process determining growth, proliferation and duration
of a Chinese hamster ovary (CHO) cell culture and influences recombinant protein
synthesis rate. During bioprocessing, CHO cells can experience stresses leading
to reprogramming of translation and decreased global protein synthesis. Here we
apply polysome profiling to determine reprogramming and translational
capabilities in host and recombinant monoclonal antibody-producing (mAb) CHO cell
lines during batch culture. Recombinant cell lines with the fastest cell specific
growth rates were those with the highest global translational efficiency.
However, total ribosomal capacity, determined from polysome profiles, did not
relate to the fastest growing or highest producing mAb cell line, suggesting it
is the ability to utilise available machinery that determines protein synthetic
capacity. Cell lines with higher cell specific productivities tended to have
elevated recombinant heavy chain transcript copy numbers, localised to the
translationally active heavy polysomes. The highest titre cell line was that
which sustained recombinant protein synthesis and maintained high recombinant
transcript copy numbers in polysomes. Investigation of specific endogenous
transcripts revealed a number that maintained or reprogrammed into heavy
polysomes, identifying targets for potential cell engineering or those with 5'
untranslated regions that might be utilised to enhance recombinant transcript
translation.
PMID- 28504351
TI - Oligonucleotide probes functionalization of nanogap electrodes.
AB - Nanogap electrodes have attracted a lot of consideration as promising platform
for molecular electronic and biomolecules detection. This is mainly for their
higher aspect ratio, and because their electrical properties are easily accessed
by current-voltage measurements. Nevertheless, application of standard current
voltages measurements used to characterize nanogap response, and/or to modify
specific nanogap electrodes properties, represents an issue. Since the strength
of electrical fields in nanoscaled devices can reach high values, even at low
voltages. Here, we analyzed the effects induced by different methods of surface
modification of nanogap electrodes, in test-voltage application, employed for the
electrical detection of a desoxyribonucleic acid (DNA) target. Nanogap electrodes
were functionalized with two antisymmetric oligo-probes designed to have 20
terminal bases complementary to the edges of the target, which after
hybridization bridges the nanogap, closing the electrical circuit. Two methods of
functionalization were studied for this purpose; a random self-assembling of a
mixture of the two oligo-probes (OPs) used in the platform, and a selective
method that controls the position of each OP at selected side of nanogap
electrodes. We used for this aim, the electrophoretic effect induced on
negatively charged probes by the application of an external direct current
voltage. The results obtained with both functionalization methods where
characterized and compared in terms of electrode surface covering, calculated by
using voltammetry analysis. Moreover, we contrasted the electrical detection of a
DNA target in the nanogap platform either in site-selective and in randomly
assembled nanogap. According to our results, a denser, although not selective
surface functionalization, is advantageous for such kind of applications.
PMID- 28504352
TI - Optimizing psychosocial adjustment after deep brain stimulation of the
subthalamic nucleus in Parkinson's disease.
PMID- 28504350
TI - The ArfGAP protein MoGlo3 regulates the development and pathogenicity of
Magnaporthe oryzae.
AB - The ADP ribosylation factor (Arf) and the coat protein complex I (COPI) are
involved in vesicle transport. Together with GTPase-activating proteins (ArfGAPs)
and guanine exchange factors (ArfGEFs) that regulate the activity of Arf, they
govern vesicle formation, COPI trafficking and the maintenance of the Golgi
complex. In an ongoing effort to study the role of membrane trafficking in
pathogenesis of the rice blast fungus Magnaporthe oryzae, we identified MoGlo3 as
an ArfGAP protein that is homologous to Glo3p of the budding yeast Saccharomyces
cerevisiae. As suspected, MoGlo3 partially complements the function of yeast
Glo3p. Consistent with findings in S. cerevisiae, MoGlo3 is localized to the
Golgi, and that the localization is dependent on the conserved BoCCS domain. We
found that MoGlo3 is highly expressed during conidiation and early infection
stages and is required for vegetative growth, conidial production and sexual
development. We further found that the DeltaMoglo3 mutant is defective in
endocytosis, scavenging of the reactive oxygen species, and in the response to
endoplasmic reticulum (ER) stress. The combined effects result in failed
appressorium function and decreased pathogenicity. Moreover, we provided evidence
showing that the domains including the GAP, BoCCS and GRM are all important for
normal MoGlo3 functions. Our studies further illustrate the importance of normal
membrane trafficking in the physiology and pathogenicity of the rice blast
fungus.
PMID- 28504353
TI - CMIP haploinsufficiency in two patients with autism spectrum disorder and co
occurring gastrointestinal issues.
AB - Autism spectrum disorder (ASD) is a genetically heterogeneous group of disorders
characterized by impairments in social communication and restricted interests.
Though some patients with ASD have an identifiable genetic cause, the cause of
most ASD remains elusive. Many ASD susceptibility loci have been identified
through clinical studies. We report two patients with syndromic ASD and
persistent gastrointestinal issues who carry de novo deletions involving the CMIP
gene detected by genome-wide SNP microarray and fluorescence in situ
hybridization (FISH) analysis. Patient 1 has a 517 kb deletion within
16q23.2q23.3 including the entire CMIP gene. Patient 2 has a 1.59 Mb deletion
within 16q23.2q23.3 that includes partial deletion of CMIP in addition to 12
other genes, none of which have a known connection to ASD or other clinical
phenotypes. The deletion of CMIP is rare in general population and was not found
among a reference cohort of approximately 12,000 patients studied in our
laboratory who underwent SNP array analysis for various indications. A 280 kb de
novo deletion containing the first 3 exons of CMIP was reported in one patient
who also demonstrated ASD and developmental delay. CMIP has previously been
identified as a susceptibility locus for specific language impairment (SLI). It
is notable that both patients in this study had significant gastrointestinal
issues requiring enteral feedings, which is unusual for patients with ASD, in
addition to unusually elevated birth length, further supporting a shared
causative gene. These findings suggest that CMIP haploinsufficiency is the likely
cause of syndromic ASD in our patients.
PMID- 28504354
TI - New methodology to reconstruct in 2-D the cuspal enamel of modern human lower
molars.
AB - OBJECTIVES: In the last years different methodologies have been developed to
reconstruct worn teeth. In this article, we propose a new 2-D methodology to
reconstruct the worn enamel of lower molars. Our main goals are to reconstruct
molars with a high level of accuracy when measuring relevant histological
variables and to validate the methodology calculating the errors associated with
the measurements. METHODS: This methodology is based on polynomial regression
equations, and has been validated using two different dental variables: cuspal
enamel thickness and crown height of the protoconid. In order to perform the
validation process, simulated worn modern human molars were employed. The
associated errors of the measurements were also estimated applying methodologies
previously proposed by other authors. RESULTS: The mean percentage error
estimated in reconstructed molars for these two variables in comparison with
their own real values is -2.17% for the cuspal enamel thickness of the protoconid
and -3.18% for the crown height of the protoconid. This error significantly
improves the results of other methodologies, both in the interobserver error and
in the accuracy of the measurements. CONCLUSIONS: The new methodology based on
polynomial regressions can be confidently applied to the reconstruction of cuspal
enamel of lower molars, as it improves the accuracy of the measurements and
reduces the interobserver error. The present study shows that it is important to
validate all methodologies in order to know the associated errors. This new
methodology can be easily exportable to other modern human populations, the human
fossil record and forensic sciences.
PMID- 28504355
TI - Home high-flow nasal cannula as a treatment for severe tracheomalacia: A
pediatric case report.
AB - Tracheomalacia refers to a softness of the tracheal cartilage that makes the
airway more susceptible to collapse. In contrast to milder cases where
conservative therapy is preferred, severe tracheomalacia is often a life
threatening condition requiring more aggressive management. For children with
this condition, a variety of treatment options are available. To our knowledge,
this is the first report of home high-flow nasal cannula as an alternative
therapy to continuous positive airway pressure (CPAP) and surgical procedures in
a pediatric patient with severe extensive tracheomalacia.
PMID- 28504356
TI - Bronchoscopy in children with tetralogy of fallot, pulmonary atresia, and major
aortopulmonary collaterals.
AB - OBJECTIVE: Children with Tetralogy of Fallot, Pulmonary Atresia, and Major
Aortopulmonary Collaterals (TOF/PA/MAPCAs) undergoing unifocalization surgery are
at risk for developing more postoperative respiratory complications than children
undergoing other types of congenital heart surgery. Bronchoscopy is used in the
perioperative period for diagnostic and therapeutic purposes. In this study, we
describe bronchoscopic findings and identify factors associated with selection
for bronchoscopy. DESIGN: Retrospective case-control. PATIENTS AND METHODS: All
patients with TOF/PA/MAPCAs who underwent unifocalization surgery from September
2005 through March 2016 were included. Patients who underwent bronchoscopy in the
perioperative period were compared to a randomly selected cohort of 172 control
patients who underwent unifocalization without bronchoscopy during the study
period. RESULTS: Forty-three children underwent perioperative bronchoscopy at a
median of 9 days postoperatively. Baseline demographics were similar in
bronchoscopy patients and controls. Patients who underwent bronchoscopy were more
likely to have a chromosome 22q11 deletion and were more likely have undergone
unifocalization surgery without intracardiac repair. These patients had a longer
duration of mechanical ventilation, ICU duration, and length of hospitalization.
Abnormalities were detected on bronchoscopy in 35 patients (81%), and 20 (35%) of
bronchoscopy patients underwent a postoperative intervention related to
abnormalities identified on bronchoscopy. CONCLUSION: Bronchoscopy is a useful
therapeutic and diagnostic instrument for children undergoing unifocalization
surgery, capable of identifying abnormalities leading to an additional
intervention in over one third of patients. Special attention should be given to
children with a 22q11 deletion to expedite diagnosis and intervention for
possible airway complications.
PMID- 28504357
TI - A nationwide seroprevalence screening for West Nile virus and Tick-borne
encephalitis virus in the population of Bulgaria.
AB - To assess local circulation and risk for human infections with West Nile virus
(WNV) and Tick-borne encephalitis virus (TBEV) in Bulgaria, a nationwide
seroprevalence study was conducted. In total, 1451 residents of all 28 districts
in Bulgaria were tested for WNV-specific and TBEV-specific IgG antibodies. The
survey found overall seroprevalence of 1.5% and 0.6%, respectively. The highest
WNV seroprevalence was found in Sofia Province and districts near the river
Danube. TBEV circulation was detected among residents of six districts. The
results showed that the two virus infections seem to be more wide-spread in the
country as has been described.
PMID- 28504358
TI - Randomized controlled trial of Functional Family Therapy for offending and
antisocial behavior in UK youth.
AB - BACKGROUND: Youth offending and antisocial behavior (ASB) are associated with low
quality mental health and relationships and usually lead to poor adult
functioning; they are very costly for society. Family interventions are effective
in children but there are few reliably effective and inexpensive interventions
for adolescents. Functional Family Therapy (FFT) is an evidence-based
intervention but seldom tested outside the United States. METHODS: One hundred
and eleven adolescents (10-17 years of age, M = 15.0, SD = 1.63) and their
families were randomized to FFT + Management As Usual (MAU) (n = 65) or to MAU (n
= 46). Assessments were made at baseline 6, and 18 months after randomization and
included interviews and questionnaires of parenting behaviors, conduct disorders
(CDs) and offending. Parent-child interaction was directly observed and police
records obtained. TRIAL REGISTRATION: ISRCTN27650478. RESULTS: Eighty-nine (80%)
were followed-up. In both groups, there were large reductions over time in all
measures of offending and antisocial behavior (e.g. primary outcome p < 0.001),
but no significant changes over time in parenting behavior or the parent-child
relationship. However, there were no differences between intervention and control
groups at 6 or 18 months on self-reported delinquency, police records of
offending, symptoms or diagnoses of CDs, parental monitoring or supervision,
directly observed child negative behavior, or parental positive or negative
behavior. Against predictions, the intervention group showed lower levels of
directly observed child positive behavior at 18 months compared to controls.
CONCLUSIONS: In contrast to most previous trials of FFT, FFT+MAU did not lead to
greater reductions in youth ASB and offending compared to MAU alone, and did not
lead to improvements in parenting or the parent-child relationship. This may be
because the trial was more rigorously conducted than prior studies; equally, the
possibility that MAU was effective requires further research.
PMID- 28504359
TI - Changing the paradigm for diagnostic MRI in pediatrics: Don't hold your breath.
AB - Increasingly complex pediatric patients and improvements in technology warrant
reevaluation of the risk associated with anesthesia for diagnostic imaging.
Although magnetic resonance imaging is the imaging modality of choice for
children given the potentially harmful effects of computerized tomography
associated ionizing radiation, we dare to suggest that certain patients would
benefit from the liberalization of our current standard. Incorporating the use of
newer computerized tomography technology may improve safety for those that are
already at higher risk for adverse events. Furthermore, magnetic resonance
imaging is not risk-free-what is often overlooked is the need for controlled
ventilation and breath-holding to minimize motion artifact. As physicians at the
forefront of the development and sustainability of the perioperative surgical
home, anesthesiologists must work to not only optimize patients preoperatively
but should also act as gatekeepers for procedural safety.
PMID- 28504360
TI - Oxygen extraction fraction mapping at 3 Tesla using an artificial neural network:
A feasibility study.
AB - PURPOSE: The oxygen extraction fraction (OEF) is an important biomarker for
tissue-viability. MRI enables noninvasive estimation of the OEF based on the
blood-oxygenation-level-dependent (BOLD) effect. Quantitative OEF-mapping is
commonly applied using least-squares regression (LSR) to an analytical tissue
model. However, the LSR method has not yet become clinically established due to
the necessity for long acquisition times. Artificial neural networks (ANNs)
recently have received increasing interest for robust curve-fitting and might
pose an alternative to the conventional LSR method for reduced acquisition times.
This study presents in vivo OEF mapping results using the conventional LSR and
the proposed ANN method. METHODS: In vivo data of five healthy volunteers and one
patient with a primary brain tumor were acquired at 3T using a gradient-echo
sampled spin-echo (GESSE) sequence. The ANN was trained with simulated BOLD data.
RESULTS: In healthy subjects, the mean OEF was 36 +/- 2% (LSR) and 40 +/- 1%
(ANN). The OEF variance within subjects was reduced from 8% to 6% using the ANN
method. In the patient, both methods revealed a distinct OEF hotspot in the tumor
area, whereas ANN showed less apparent artifacts in surrounding tissue.
CONCLUSION: In clinical scan times, the ANN analysis enables OEF mapping with
reduced variance, which could facilitate its integration into clinical protocols.
Magn Reson Med 79:890-899, 2018. (c) 2017 International Society for Magnetic
Resonance in Medicine.
PMID- 28504362
TI - Synthesis and structure elucidation of polyphenols containing the N'
methyleneformohydrazide scaffold as aurora kinase inhibitors.
PMID- 28504361
TI - Alterations of resting-state fMRI measurements in individuals with cervical
dystonia.
AB - Cervical dystonia (CD) is a neurological disorder with typical symptoms of
involuntary and abnormal movements and postures of the head. CD-associated
alterations of functional brain networks have not been well characterized.
Previous studies of CD using resting-state functional MRI (rfMRI) are limited in
two aspects: (i) the analyses were not directly focused on the functional brain
network related to head movement and (ii) rfMRI measurements other than
functional connectivity (FC) were not investigated. The present study examined
alterations of FC in CD by capitalizing on newly identified brain regions
supporting isometric head rotation (Prudente et al.: J Neurosci 35 (2015) 9163
9172). In addition to FC, which only reflects inter-regional signal
synchronization, local, or intraregional alterations were also examined using
rfMRI measurements of the fractional amplitude of low-frequency fluctuations and
regional homogeneity (ReHo). Finally, with alterations of different rfMRI
measures identified, a support vector machine (SVM) learning algorithm was
implemented for group classification. The results revealed both inter- (FC) and
intra-regional (ReHo) alterations extensively distributed in both cortical and
subcortical structures; and common alterations of these measures were identified
bilaterally in the postcentral gyrus as well as in the basal ganglia and
thalamus. Of the rfMRI features examined, seven of them (four FC and three ReHo
measures) survived the SVM procedure of recursive feature elimination and
together provided the highest group classification accuracy of 90.6%. The present
findings extend previous studies of rfMRI in CD and offer insight into the
underlying pathophysiology of the disorder in relation to network dysfunction and
somatosensory disturbances. Hum Brain Mapp 38:4098-4108, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28504363
TI - Allergic contact dermatitis caused by (meth)acrylates in nail cosmetic products
in users and nail technicians - a 5-year study.
AB - BACKGROUND: The increasing use of long-lasting nail aesthetic products has led to
a growing number of cases of allergic contact dermatitis (ACD) caused by
(meth)acrylates in recent years. OBJECTIVES: To provide information on ACD caused
by (meth)acrylates related to nail cosmetic products. METHODS: We retrospectively
reviewed files of patients with ACD caused by (meth)acrylates related to nail
cosmetic products, who were patch tested between January 2011 and December 2015
in 13 departments of dermatology in Portugal. RESULTS: Two-hundred and thirty
cases of ACD caused by (meth)acrylates (55 technicians, 56 consumers, and 119
with mixed exposure) had been documented, mostly as chronic hand eczema (93%).
The most common sensitizers were: 2-hydroxyethyl methacrylate (HEMA), which was
positive in 90% of the tested patients, 2-hydroxypropyl methacrylate (HPMA),
which was positive in 64.1%, and ethyleneglycol dimethacrylate, which was
positive in 54.5%. CONCLUSION: HEMA and HPMA were the most frequent positive
allergens. HEMA, which identified 90% of cases, can be considered to be a good
screening allergen. The high number of cases of ACD caused by (meth)acrylates in
nail cosmetic products certainly warrants better preventive measures at the
occupational level, and specific regulation in the field of consumer safety.
PMID- 28504364
TI - Mindfulness meditation regulates anterior insula activity during empathy for
social pain.
AB - Mindfulness has been shown to reduce stress, promote health, and well-being, as
well as to increase compassionate behavior toward others. It reduces distress to
one's own painful experiences, going along with altered neural responses, by
enhancing self-regulatory processes and decreasing emotional reactivity. In order
to investigate if mindfulness similarly reduces distress and neural activations
associated with empathy for others' socially painful experiences, which might in
the following more strongly motivate prosocial behavior, the present study
compared trait, and state effects of long-term mindfulness meditation (LTM)
practice. To do so we acquired behavioral data and neural activity measures using
functional magnetic resonance imaging (fMRI) during an empathy for social pain
task while manipulating the meditation state between two groups of LTM
practitioners that were matched with a control group. The results show increased
activations of the anterior insula (AI) and anterior cingulate cortex (ACC) as
well as the medial prefrontal cortex and temporal pole when sharing others'
social suffering, both in LTM practitioners and controls. However, in LTM
practitioners, who practiced mindfulness meditation just prior to observing
others' social pain, left AI activation was lower and the strength of AI
activation following the mindfulness meditation was negatively associated with
trait compassion in LTM practitioners. The findings suggest that current
mindfulness meditation could provide an adaptive mechanism in coping with
distress due to the empathic sharing of others' suffering, thereby possibly
enabling compassionate behavior. Hum Brain Mapp 38:4034-4046, 2017. (c) 2017
Wiley Periodicals, Inc.
PMID- 28504365
TI - Cost-effectiveness of non-surgical periodontal therapy for patients with type 2
diabetes in the UK.
AB - AIM: Periodontal therapy has been shown to reduce glycated haemoglobin in
patients with diabetes, although considerable uncertainty remains regarding the
sustainability of such changes. We evaluate the cost-effectiveness of non
surgical periodontal therapy and rigorous maintenance treatment in patients with
type 2 diabetes and periodontitis from a provider perspective in the UK. METHOD:
Lifetime costs relating to periodontal treatment were modelled for a cohort of
patients with type 2 diabetes. The projected lifetime impact of changes in
glycated haemoglobin on diabetes treatment costs and quality adjusted life
expectancy were estimated from a published simulation model. Costs and outcomes
were combined to estimate the Incremental Cost-Effectiveness Ratio for
periodontal therapy in patients with type 2 diabetes. RESULTS: The Incremental
Cost-Effectiveness Ratio was L28,000 per Quality Adjusted Life-Year for a man
aged 58 with glycated haemoglobin of 7%-7.9%. The results were particularly
sensitive to assumptions on the impact of periodontal therapy on glycated
haemoglobin, the proportion of patients who comply with maintenance therapy and
the proportion of compliant patients who respond to treatment. CONCLUSION:
Assuming improvements in glycated haemoglobin can be maintained, periodontal
therapy may be cost-effective for patients with type 2 diabetes at acceptable
cost-per-Quality Adjusted Life-Year thresholds in the UK.
PMID- 28504366
TI - Mechanochemical Synthesis of Phosphazane-Based Frameworks.
AB - Mechanochemistry is emerging as a powerful solvent-free approach to chemical
synthesis, having been applied to metal oxides, pharmaceutical materials, organic
compounds and to a lesser extent, coordination complex synthesis. Notably,
examples of applications of mechanochemical methodologies in the synthesis of
main-group compounds are few and far between. Herein, we demonstrate that ball
milling enabled the solvent-free synthesis of a range of phosphazane frameworks
with a broad substrate scope, yielding seven new acyclic and macrocyclic species.
The strength of this methodology is highlighted by a fast, selective and high
conversion product generation from poorly soluble starting materials, thereby
demonstrating mechanochemistry as a real alternative to solution-based methods in
synthetic main-group chemistry.
PMID- 28504368
TI - Chemical Institute of Canada and Canadian Society for Chemistry Awards.
PMID- 28504367
TI - Neuroprotective Natural Products for the Treatment of Parkinson's Disease by
Targeting the Autophagy-Lysosome Pathway: A Systematic Review.
AB - The autophagy-lysosome pathway (ALP) is a primary means by which damaged
organelles and long-lived proteins are removed from cells and their components
recycled. Impairment of the ALP has been found to be linked to the pathogenesis
of Parkinson's disease (PD), a chronic neurodegenerative disorder characterized
by the accumulation of protein aggregates and loss of dopaminergic neurons in the
midbrain. In recent years, some active compounds derived from plants have been
found to regulate the ALP and to exert neuroprotective effects in experimental
models of PD, raising the possibility that autophagy enhancement may be an
effective therapeutic strategy in PD treatment. In this review, we summarize
recent findings of natural products that enhance ALP and thereby protect against
PD. Research articles were retrieved from PubMed using relevant keywords in
combination. Papers related to the topic were identified, and then the
reliability of the experiments was assessed in terms of methodology. The results
suggest that targeting the ALP with natural products is a promising strategy for
PD treatment. However, risk of bias exists in some studies due to the defective
methodology. Rigorous experimental design following the guidelines of autophagy
assays, molecular target identification and in vivo efficacy evaluation is
critical for the development of ALP enhancers for PD treatment in future studies.
Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28504370
TI - Topical photodynamic therapy: the preferred choice for cutaneous field
cancerization?
PMID- 28504371
TI - Image Gallery: Massive localized lymphoedema.
PMID- 28504373
TI - Psoriasis and osteoporosis: the debate continues.
PMID- 28504374
TI - Melanoma risk in congenital melanocytic naevi.
PMID- 28504375
TI - Image Gallery: Generalized mucosal and cutaneous papillomatosis, a unique sign of
malignant acanthosis nigricans.
PMID- 28504377
TI - Interleukin-10-producing B-cells in autoimmune bullous diseases.
PMID- 28504379
TI - T-type calcium channels as potential biomarkers in melanoma.
PMID- 28504381
TI - Estimating the future health service burden of keratinocyte cancers in the U.K.
PMID- 28504382
TI - Further evidence for carotenoid antioxidants in photoprotection.
PMID- 28504384
TI - Image Gallery: Mucormycosis.
PMID- 28504386
TI - Corrigendum.
PMID- 28504387
TI - Corrigenda.
PMID- 28504385
TI - Home phototherapy in the U.K.'s National Health Service: time to reach out.
PMID- 28504388
TI - Challenges of treating melanoma in situ, lentigo maligna type: is pathological
clearance the gold standard?
PMID- 28504389
TI - Research questions for the treatment of alopecia areata have been prioritized.
PMID- 28504390
TI - Identification of pharmacogenetic markers of treatment response to biologic
therapies in psoriasis - is there a benefit?
PMID- 28504391
TI - The impact of skin conditions on generic health-related quality of life.
PMID- 28504392
TI - Molecular diagnosis of xeroderma pigmentosum variant in an isolated population:
the interface between precision medicine and public health.
PMID- 28504393
TI - Incorporating hair follicle cells in artificial skin.
PMID- 28504394
TI - Image Gallery: Acute primary cutaneous nocardiosis due to Nocardia brasiliensis.
PMID- 28504395
TI - Corrigendum.
PMID- 28504396
TI - Psoriasis: inequality or individualized care?
PMID- 28504397
TI - Hair-follicle dermal papilla and sheath fibroblasts provide a supportive
microenvironment for human skin regeneration.
PMID- 28504398
TI - Image Gallery: Palmoplantar hyperkeratosis in dermatomyositis with anti-PM/Scl
antibodies.
PMID- 28504399
TI - Aggression and its associations in patients with skin disease.
PMID- 28504401
TI - Image Gallery: A case of pemphigus vulgaris following Simulium spp. (Diptera)
bites.
PMID- 28504402
TI - Epidermal growth factor receptor gaining impact in cutaneous squamous cell
carcinoma.
PMID- 28504403
TI - Long methylaminolaevulinate application does not increase clinical efficacy of
photodynamic therapy in actinic keratosis, but leads to collateral damage.
PMID- 28504404
TI - Prognostic factors in mycosis fungoides: international advances in the validation
of prognostic indices.
PMID- 28504405
TI - Image Gallery: Resolution of lichen striatus in a patient with coexisting chronic
plaque psoriasis and vitiligo during secukinumab treatment.
PMID- 28504406
TI - Corrigendum.
PMID- 28504407
TI - Effects of space allocations and energy levels on growth performance and nutrient
digestibility in growing and finishing pigs.
AB - Two experiments were conducted to investigate effects of different space
allocations and different dietary metabolizable energy (ME) levels on growth
performance and nutrient digestibility in growing and finishing pigs. In
experiment 1, a total of 84 growing pigs [(Yorkshire * Landrace) * Duroc] with an
initial body weight (BW) of 27.10 +/- 1.60 kg were used in a 5-week trial. Pigs
were blocked based on initial BW into a 2 * 2 factorial design with the following
factors: (i) 0.60 or 0.80 m2 /pig space allocations; and (ii) 3,400 or 3,550
kcal/kg ME of diets. In experiment 2, a total of 84 finishing pigs with an
initial BW of 67.43 +/- 1.97 kg were used in a 10-week trial. Pigs were allotted
based on initial BW into a 2 * 2 factorial design with the following factors: (i)
0.81 or 1.08 m2 /pig space allocations; and (ii) 3,300 or 3,450 kcal/kg ME of
diet. In experiment 1, high ME diet improved gain-to-feed ratio (G:F) in pigs
with low space allocation but not in pigs in high space allocation (p < .05).
Additionally, high ME diet increased apparent total tract digestibility (ATTD) of
nitrogen in low space allocation but decreased ATTD of nitrogen in high space
allocation (p < .05). In experiment 2, high ME diet improved average daily gain
(ADG) and G:F in early-finishing pigs with low space allocation but not in pigs
with high space allocation (p < .05). In conclusion, the provision of high ME
diets was not enough to overcome the reduction in growth performance due to low
space allocation but can improve feed efficiency in growing pigs and daily gain
and feed efficiency early-finishing pigs.
PMID- 28504408
TI - Kv1.3 channels facilitate the connection between metabolism and blood flow in the
heart.
AB - The connection between metabolism and flow in the heart, metabolic dilation, is
essential for cardiac function. We recently found redox-sensitive Kv1.5 channels
play a role in coronary metabolic dilation; however, more than one ion channel
likely plays a role in this process as animals null for these channels still
showed limited coronary metabolic dilation. Accordingly, we examined the role of
another Kv1 family channel, the energetically linked Kv1.3 channel, in coronary
metabolic dilation. We measured myocardial blood flow (contrast echocardiography)
during norepinephrine-induced increases in cardiac work (heart rate x mean
arterial pressure) in WT, WT mice given correolide (preferential Kv1.3
antagonist), and Kv1.3-null mice (Kv1.3-/- ). We also measured relaxation of
isolated small arteries mounted in a myograph. During increased cardiac work,
myocardial blood flow was attenuated in Kv1.3-/- and in correolide-treated mice.
In isolated vessels from Kv1.3-/- mice, relaxation to H2 O2 was impaired (vs WT),
but responses to adenosine and acetylcholine were equivalent to WT. Correolide
reduced dilation to adenosine and acetylcholine in WT and Kv1.3-/- , but had no
effect on H2 O2 -dependent dilation in vessels from Kv1.3-/- mice. We conclude
that Kv1.3 channels participate in the connection between myocardial blood flow
and cardiac metabolism.
PMID- 28504410
TI - Unpacking the Ontogeny of Gesture Understanding: How Movement Becomes Meaningful
Across Development.
AB - Gestures, hand movements that accompany speech, affect children's learning,
memory, and thinking (e.g., Goldin-Meadow, 2003). However, it remains unknown how
children distinguish gestures from other kinds of actions. In this study, 4- to 9
year-olds (n = 339) and adults (n = 50) described one of three scenes: (a) an
actor moving objects, (b) an actor moving her hands in the presence of objects
(but not touching them), or (c) an actor moving her hands in the absence of
objects. Participants across all ages were equally able to identify actions on
objects as goal directed, but the ability to identify empty-handed movements as
representational actions (i.e., as gestures) increased with age and was
influenced by the presence of objects, especially in older children.
PMID- 28504411
TI - Directed C-H Activation and Tandem Cross-Coupling Reactions Using Palladium
Nanocatalysts with Controlled Oxidation.
AB - Controlled oxidation of palladium nanoparticles provided high-valent PdIV oxo
clusters which efficiently promote directed C-H halogenation reactions. In
addition, palladium nanoparticles can undergo changes in oxidation states to
provide both high-valent PdIV and low-valent Pd0 species within one system, and
thus a tandem reaction of C-H halogenation and cross-coupling (C-N, C-C, and C-S
bond formation) was successfully established.
PMID- 28504412
TI - Globalism versus Nationalism in Medical Physics.
PMID- 28504413
TI - [60]Fullerene-Based Macrocycle Ligands.
AB - Macrocycle ligands have three or more donor sites. Selective replacement of
skeleton carbon atoms by heteroatoms and vacancies in C60 could lead to various
macrocycle ligands with a cage-shaped backbone. Theoretical calculations indicate
that such C60 -based macrocycle ligands are as stable as C60 thermodynamically
according to their similar HOMO-LUMO gaps. The synthesis of these ligands is a
challenging task. Nevertheless important progresses have been reported. This
concept article focuses on the structures of possible C60 -based macrocycle
ligands and related synthetic results.
PMID- 28504409
TI - Multifunctional Liposomes for Image-Guided Intratumoral Chemo-Phototherapy.
AB - Intratumoral (IT) drug injections reduce systemic toxicity, but delivered volumes
and distribution can be inconsistent. To improve IT delivery paradigms, porphyrin
phospholipid (PoP) liposomes are passively loaded with three hydrophilic cargos:
sulforhodamine B, a fluorophore; gadolinium-gadopentetic acid, a magnetic
resonance (MR) agent; and oxaliplatin, a colorectal cancer chemotherapeutic.
Liposome composition is optimized so that cargo is retained in serum and storage,
but is released in less than 1 min with exposure to near infrared light. Light
triggered release occurs with PoP-induced photooxidation of unsaturated lipids
and all cargos release concurrently. In subcutaneous murine colorectal tumors,
drainage of released cargo is delayed when laser treatment occurs 24 h after IT
injection, at doses orders of magnitude lower than systemic ones. Delayed light
triggering results in substantial tumor shrinkage relative to controls a week
following treatment, although regrowth occurs subsequently. MR imaging reveals
that over this time frame, pools of liposomes within the tumor migrate to
adjacent regions, possibly leading to altered spatial distribution during
triggered drug release. Although further characterization of cargo loading and
release is required, this proof-of-principle study suggests that multimodal
theranostic IT delivery approaches hold potential to both guide injections and
interpret outcomes, in particular when combined with chemo-phototherapy.
PMID- 28504414
TI - High-Molecular-Weight Polynucleotides by Transferase-Catalyzed Living Chain
Growth Polycondensation.
AB - We present terminal deoxynucleotidyl transferase-catalyzed enzymatic
polymerization (TcEP) for the template-free synthesis of high-molecular-weight,
single-stranded DNA (ssDNA) and demonstrate that it proceeds by a living chain
growth polycondensation mechanism. We show that the molecular weight of the
reaction products is nearly monodisperse, and can be manipulated by the feed
ratio of nucleotide (monomer) to oligonucleotide (initiator), as typically
observed for living polymerization reactions. Understanding the synthesis
mechanism and the reaction kinetics enables the rational, template-free synthesis
of ssDNA that can be used for a range of biomedical and nanotechnology
applications.
PMID- 28504415
TI - Highly Luminescent Folate-Functionalized Au22 Nanoclusters for Bioimaging.
AB - Gold nanoclusters are emerging as new materials for biomedical applications
because of promises offered by their ultrasmall size and excellent
biocompatibility. Here, the synthesis and optical and biological
characterizations of a highly luminescent folate-functionalized Au22 cluster
(Au22 -FA) are reported. The Au22 -FA clusters are synthesized by functionalizing
the surface of Au22 (SG)18 clusters, where SG is glutathione, with benzyl
chloroformate and folate. The functionalized clusters are highly water-soluble
and exhibit remarkably bright luminescence with a quantum yield of 42%,
significantly higher than any other water-soluble gold clusters protected with
thiolate ligands. The folate groups conjugated to the gold cluster give rise to
additional luminescence enhancement by energy transfer sensitization. The
brightness of Au22 -FA is found to be 4.77 mM-1 cm-1 , nearly 8-fold brighter
than that of Au22 (SG)18 . Further biological characterizations have revealed
that the Au22 -FA clusters are well-suited for bioimaging. The Au22 -FA clusters
exhibit excellent photostability and low toxicity; nearly 80% cell viability at
1000 ppm of the cluster. Additionally, the Au22 -FA clusters show target
specificity to folate-receptor positive cells. Finally, the time-course in vivo
luminescence images of intravenous-injected mice show that the Au22 -FA clusters
are renal-clearable, leaving only 8% of them remained in the body after 24 h post
injection.
PMID- 28504416
TI - Characterization and circulation of seasonal influenza viruses in Madrid, 2010
2016.
AB - Influenza virus infection is a major health care burden and is associated with
significant morbidity and mortality. The 2009 influenza pandemic highlighted the
importance of influenza surveillance. The objective of this study was to assess
the epidemiology and activity of influenza A and B viruses in adults and children
in the post-pandemic period with a special focus on the pediatric population. We
performed a retrospective descriptive study involving adults and children with
influenza-like illness at the Clinico San Carlos Hospital (Madrid, Spain) over
six influenza seasons, between August 2010 and April 2016. Respiratory specimens
were collected from 3131 patients and routinely processed for influenza
diagnosis. Epidemiological analysis was performed in terms of gender, age, and
seasonal distribution. Globally, Influenza A and B viruses were detected in the
respiratory specimens of 696 (22.2%) of the 3131 studied population. Among all
influenza positive specimens, 142 (20.4%) were influenza A(H1N1)pdm09, 61 (8.8%)
were influenza A(H3N2), 321 (46.1%) were untypeable influenza A viruses and 166
(23.9%) were influenza B. Co-infection by both influenza A and B viruses was
detected in six patients (0.9%). Meanwhile, co-infection with other non-influenza
respiratory viruses was identified in 5 children and 20 adults. Influenza
A(H1N1)pdm09 virus activity has been significantly high since the 2009 pandemic
and has gradually replaced the previously circulating seasonal influenza A(H1N1)
virus. Moreover, influenza A(H3N2) virus activity remained at low levels during
the last winter season while influenza B virus isolates increased significantly
over the past 2 years.
PMID- 28504417
TI - Laser-preparation of geometrically optimised samples for X-ray nano-CT.
AB - A robust and versatile sample preparation technique for the fabrication of
cylindrical pillars for imaging by X-ray nano-computed tomography (nano-CT) is
presented. The procedure employs simple, cost-effective laser micro-machining
coupled with focused-ion beam (FIB) milling, when required, to yield mechanically
robust samples at the micrometre length-scale to match the field-of-view (FOV)
for nano-CT imaging. A variety of energy and geological materials are exhibited
as case studies, demonstrating the procedure can be applied to a variety of
materials to provide geometrically optimised samples whose size and shape are
tailored to the attenuation coefficients of the constituent phases. The procedure
can be implemented for the bespoke preparation of pillars for both lab- and
synchrotron-based X-ray nano-CT investigations of a wide range of samples.
PMID- 28504418
TI - High-Flux Carbon Molecular Sieve Membranes for Gas Separation.
AB - Carbon membranes have great potential for highly selective and cost-efficient gas
separation. Carbon is chemically stable and it is relative cheap. The controlled
carbonization of a polymer coating on a porous ceramic support provides a 3D
carbon material with molecular sieving permeation performance. The carbonization
of the polymer blend gives turbostratic carbon domains of randomly stacked
together sp2 hybridized carbon sheets as well as sp3 hybridized amorphous carbon.
In the evaluation of the carbon molecular sieve membrane, hydrogen could be
separated from propane with a selectivity of 10 000 with a hydrogen permeance of
5 m3 (STP)/(m2 hbar). Furthermore, by a post-synthesis oxidative treatment, the
permeation fluxes are increased by widening the pores, and the molecular sieve
carbon membrane is transformed from a molecular sieve carbon into a selective
surface flow carbon membrane with adsorption controlled performance and becomes
selective for carbon dioxide.
PMID- 28504419
TI - Congenital nephrogenic diabetes insipidus complicated with Hinman syndrome.
PMID- 28504420
TI - Use of Supramolecular Assemblies as Lithographic Resists.
AB - A new resist material for electron beam lithography has been created that is
based on a supramolecular assembly. Initial studies revealed that with this
supramolecular approach, high-resolution structures can be written that show
unprecedented selectivity when exposed to etching conditions involving plasmas.
PMID- 28504421
TI - Bioinformatics Analysis on Molecular Mechanism of Green Tea Compound
Epigallocatechin-3-Gallate Against Ovarian Cancer.
AB - Epigallocatechin-3-gallate (EGCG) is the most abundant and biologically active
catechin in green tea, and it exerts multiple effects in humans through
mechanisms that remain to be clarified. The present study used bioinformatics to
identify possible mechanisms by which EGCG reduces the risk of ovarian cancer.
Possible human protein targets of EGCG were identified in the PubChem database,
possible human gene targets were identified in the National Center for
Biotechnology Information database, and then both sets of targets were analyzed
using Ingenuity Pathway Analysis (IPA). The results suggest that signaling
proteins affected by EGCG in ovarian cancer, which include JUN, FADD, NFKB1, Bcl
2, HIF1alpha, and MMP, are involved primarily in cell cycle, cellular assembly
and organization, DNA replication, etc. These results identify several specific
proteins and pathways that may be affected by EGCG in ovarian cancer, and they
illustrate the power of integrative informatics and chemical fragment analysis
for focusing mechanistic studies.
PMID- 28504422
TI - Effects of Mobile Phones on Children's and Adolescents' Health: A Commentary.
AB - The use of digital technology has grown rapidly during the last couple of
decades. During use, mobile phones and cordless phones emit radiofrequency (RF)
radiation. No previous generation has been exposed during childhood and
adolescence to this kind of radiation. The brain is the main target organ for RF
emissions from the handheld wireless phone. An evaluation of the scientific
evidence on the brain tumor risk was made in May 2011 by the International Agency
for Research on Cancer at World Health Organization. The scientific panel reached
the conclusion that RF radiation from devices that emit nonionizing RF radiation
in the frequency range 30 kHz-300 GHz is a Group 2B, that is, a "possible" human
carcinogen. With respect to health implications of digital (wireless)
technologies, it is of importance that neurological diseases, physiological
addiction, cognition, sleep, and behavioral problems are considered in addition
to cancer. Well-being needs to be carefully evaluated as an effect of changed
behavior in children and adolescents through their interactions with modern
digital technologies.
PMID- 28504424
TI - The current state of postoperative imaging in the presence of deep brain
stimulation electrodes.
PMID- 28504423
TI - Genetic vulnerabilities to prenatal alcohol exposure: Limb defects in sonic
hedgehog and GLI2 heterozygous mice.
AB - BACKGROUND: Genetic factors influence the physical and neurobehavioral
manifestations of prenatal alcohol exposure (PAE). Animal models allow the
investigation of specific genes that confer vulnerability to, or protection from,
birth defects associated with fetal alcohol spectrum disorders (FASDs). The
objective of the present experiments was to determine if genetic alterations in
the Sonic Hedgehog (Shh) signaling pathways affect the vulnerability to PAE
induced skeletal defects involving the forelimbs and/or hindlimbs. METHOD: Wild
type C57BL/6J female mice were bred with males in which one copy of the Shh or
Gli2 genes had been knocked out, to produce litters with both wild-type (+/+) and
heterozygous (+/-) embryos. Alcohol doses (two injections of 2.9 g/kg, 4 hours
apart) or vehicles were administered starting at gestational day (GD) 9.25, 9.5,
or 9.75, a critical exposure time for inducing limb defects. Limb defects were
examined at GD 17 using a dysmorphology scale based on abnormalities ranging from
increased interdigital spacing to the deletion of multiple fingers and the ulna.
RESULTS: Alcohol treatment caused a high incidence of forelimb defects,
particularly on the right side, that was higher in Shh+/- and Gli2+/- fetuses
compared to wild-type fetuses. Dysmorphology scores were also significantly
higher in the Shh+/- and Gli2+/- mice. CONCLUSIONS: These results extend previous
findings demonstrating enhanced sensitivity to PAE-induced craniofacial
dysmorphology and support the hypothesis that genetic alterations in the Shh
signaling pathway influences the vulnerability to alcohol-induced birth defects.
Moreover, these results emphasize the importance of understanding the
interactions between genes and prenatal exposure to alcohol or other teratogens.
Birth Defects Research 109:860-865, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28504425
TI - Active surveillance to update county scale distribution of four tick species of
medical and veterinary importance in Oklahoma.
AB - The incidence of tick-borne disease continues to increase in humans and companion
animals in the United States, yet distribution maps for several tick vectors in
Oklahoma, including Dermacentor variabilis, Dermacentor albipictus, Ixodes
scapularis, and Amblyomma maculatum, are not available or are outdated. To
address this issue, county-scale tick records from peer-reviewed literature and
passive collections were reviewed for Oklahoma. Additionally, dry ice traps, tick
drags, and harvested deer were utilized to actively collect adult ticks
throughout the state. Through these methods, D. variabilis, D. albipictus, I.
scapularis, and A. maculatum were identified in 88% (68/77), 45.4% (35/77), 66.2%
(51/77), and 64.9% (50/77) of the counties in Oklahoma, respectively. Baseline
maps were developed for the distribution of D. variabilis and D. albipictus and
distribution maps were updated for I. scapularis and A. maculatum. This data
confirms that these four species of ticks continue to be widespread within
Oklahoma with a western expansion of the range of I. scapularis within the state.
These results assist efforts to better understand the epidemiology of the
different diseases caused by pathogens transmitted by these tick species within
the Great Plains region.
PMID- 28504426
TI - Mosquito distribution in a saltmarsh: determinants of eggs in a variable
environment.
AB - Two saltmarsh mosquitoes dominate the transmission of Ross River virus (RRV,
Togoviridae: Alphavirus), one of Australia's most prominent mosquito-borne
diseases. Ecologically, saltmarshes vary in their structure, including habitat
types, hydrological regimes, and diversity of aquatic fauna, all of which drive
mosquito oviposition behavior. Understanding the distribution of vector
mosquitoes within saltmarshes can inform early warning systems, surveillance, and
management of vector populations. The aim of this study was to identify the
distribution of Ae. camptorhynchus, a known vector for RRV, across a saltmarsh
and investigate the influence that other invertebrate assemblage might have on
Ae. camptorhynchus egg dispersal. We demonstrate that vegetation is a strong
indicator for Ae. camptorhynchus egg distribution, and this was not correlated
with elevation or other invertebrates located at this saltmarsh. Also, habitats
within this marsh are less frequently inundated, resulting in dryer conditions.
We conclude that this information can be applied in vector surveillance and
monitoring of temperate saltmarsh environments and also provides a baseline for
future investigations into understanding mosquito vector habitat requirements.
PMID- 28504428
TI - The effect of inbreeding and larval feeding regime on immature development of
Aedes albopictus.
AB - The fundamental approach to the biological control of Aedes albopictus requires
the mass rearing of mosquitoes and the release of highly competitive adults in
the field. As the fitness of adults is highly dependent on the development of
immatures, we aimed to identify the minimum feeding regime required to produce
viable and competitive adults by evaluating three response parameters:
development duration, immature mortality, and adult wing length. Our study
suggests at least 0.60 mg/larva/day of larval diet composed of dog food, dried
beef liver, yeast, and milk powder in a weight ratio of 2:1:1:1 is required to
maximize adult fitness. With standardized protocols in mass rearing, intensive
studies can be readily conducted on mosquito colonies to facilitate comparisons
across laboratories. This study also evaluated the differences in response of
laboratory and field strains under different feeding regimes. We found that
strain alone did not exert substantial effects on all response parameters.
However, the field strain exhibited significantly lower immature mortality than
the laboratory strain under the minimum feeding regime. Females and males of the
laboratory strain had longer wing lengths under nutritional constraint due to the
higher mortality that resulted in reduced interactions with the remaining larvae.
Meanwhile, the field strain exhibited heterogeneous duration of immature
development compared with the laboratory strain. The disparities demonstrated by
the two strains in this study suggest the effect of inbreeding surfaced after a
long term of laboratory colonization. Despite the trade-offs resulting from
laboratory colonization, the competitiveness of the laboratory strain of Ae.
albopictus is comparable to the field strain, provided the larvae are fed
optimally.
PMID- 28504429
TI - Species composition and temporal distribution of adult ixodid ticks and
prevalence of Borrelia burgdorferi sensu lato and Rickettsia species in Orange
County, California.
PMID- 28504430
TI - Variation of tsetse fly abundance in relation to habitat and host presence in the
Maasai Steppe, Tanzania.
AB - Human activities modify ecosystem structure and function and can also alter the
vital rates of vectors and thus the risk of infection with vector-borne diseases.
In the Maasai Steppe ecosystem of northern Tanzania, local communities depend on
livestock and suitable pasture that is shared with wildlife, which can increase
tsetse abundance and the risk of trypanosomiasis. We monitored the monthly tsetse
fly abundance adjacent to Tarangire National Park in 2014-2015 using geo
referenced, baited epsilon traps. We examined the effect of habitat types and
vegetation greenness (NDVI) on the relative abundance of tsetse fly species. Host
availability (livestock and wildlife) was also recorded within 100*100 m of each
trap site. The highest tsetse abundance was found in the ecotone between Acacia
Commiphora woodland and grassland, and the lowest in riverine woodland. Glossina
swynnertoni was the most abundant species (68%) trapped throughout the entire
study, while G. pallidipes was the least common (4%). Relative species abundance
was negatively associated with NDVI, with greatest abundance observed in the dry
season. The relationship with the abundance of wildlife and livestock was more
complex, as we found positive and negative associations depending on the host and
fly species. While habitat is important for tsetse distribution, hosts also play
a critical role in affecting fly abundance and, potentially, trypanosomiasis
risk.
PMID- 28504431
TI - The mosquito fauna of the western region of Spain with emphasis on ecological
factors and the characterization of Culex pipiens forms.
AB - : This study updates the diversity, distribution, and seasonal trends of
mosquitoes in a western region of Spain, assesses ecological determinants of
Culex pipiens s.l., and determines form composition of Cx. pipiens s.s.
POPULATIONS: A total of 1,495 mosquitoes of 16 species was collected during 2012
2013, of which Cx. pipiens s.l. and Cx. theileri were the most abundant. Five new
records for An. maculipennis s.s., Orthopodomyia pulcripalpis, Aedes
(Ochlerotatus) punctor, Cx. europaeus, and Cx. modestus were found for this
region. Cx. pipiens density varied across weather and habitat patterns,
correlating positively with high temperatures and with a preference for urbanized
areas and rural areas within a proximity of ovine farms. Moreover, molecular
identification by CQ11FL was performed in 467 Cx. pipiens s.s., detecting both
pipiens (66%) and molestus (8.4%) forms coexisting in different habitats (urban,
peri-urban and rural) aboveground with a high degree of hybridization (25.7%).
The abundance of Cx. pipiens in urban areas and farms, with the presence of
hybrids, may increase their capacity to act as bridge vectors for the
transmission of arboviral infections. These data will be helpful for further
implementation of entomological programs focused on risk assessment for
arboviruses or other mosquito-borne pathogens.
PMID- 28504432
TI - Control of male Aedes albopictus Skuse (Diptera: Culicidae) using boric acid
sugar bait and its impact on female fecundity and fertility.
PMID- 28504433
TI - Influence of shading and pedestrian traffic on the preference of Aedes
(Stegomyia) aegypti (Diptera: Culicidae) for oviposition microenvironments.
AB - Aedes aegypti mosquitoes are highly adaptable to abiotic stimuli. To evaluate the
influence of shading and pedestrian traffic on the preference of Ae. aegypti for
oviposition microenvironments, 20 sites were sampled weekly using ovitraps within
the perimeter of Universidade Federal do Espirito Santo, located in Sao Mateus,
Espirito Santo, Brazil. A spatial and statistical analysis was performed in order
to assess the relationship between shading time, pedestrian traffic, and the
presence of biological forms of Ae. aegypti. A temporal analysis of temperature
and precipitation influence on oviposition was also made. Between June, 2013 and
June, 2014, 7,362 Ae. aegypti eggs were collected. Over a 12-month period, we
made weekly collections of Ae. aegypti eggs from ovitraps. Pedestrian traffic and
shading time influenced the number of positive ovitraps; precipitation and
temperature were correlated with the number of positive ovitraps (p <0.05). We
conclude that the influence of temperature and precipitation was not significant
for the oviposition index, and the frequency of oviposition was directly
proportional to the number of individuals moving close to the traps during
periods of greater shading.
PMID- 28504435
TI - An updated checklist of the Culicidae (Diptera) of Morocco, with notes on species
of historical and current medical importance.
AB - An updated checklist of the mosquito species (Diptera: Culicidae) recorded in
Morocco from 1916 to 2016 is provided, including synonyms and synonymous usage
for each species. Forty-three species belonging to seven genera are recorded so
far: Anopheles (9), Aedes (12) Coquillettidia (2), Culex (12), Culiseta (5),
Orthopodomyia (1) and Uranotaenia (2). Traditional and equivalent names in the
polyphyletic concept of Aedes are provided for the aedine species. The historical
importance and current potential threat of mosquitoes to human health in Morocco
is reviewed.
PMID- 28504436
TI - Mosquito species distribution across urban, suburban, and semi-rural residences
in San Antonio, Texas.
PMID- 28504437
TI - Seasonal variation of tsetse fly species abundance and prevalence of trypanosomes
in the Maasai Steppe, Tanzania.
AB - Tsetse flies, the vectors of trypanosomiasis, represent a threat to public health
and economy in sub-Saharan Africa. Despite these concerns, information on
temporal and spatial dynamics of tsetse and trypanosomes remain limited and may
be a reason that control strategies are less effective. The current study
assessed the temporal variation of the relative abundance of tsetse fly species
and trypanosome prevalence in relation to climate in the Maasai Steppe of
Tanzania in 2014-2015. Tsetse flies were captured using odor-baited Epsilon traps
deployed in ten sites selected through random subsampling of the major vegetation
types in the area. Fly species were identified morphologically and trypanosome
species classified using PCR. The climate dataset was acquired from the African
Flood and Drought Monitor repository. Three species of tsetse flies were
identified: G. swynnertoni (70.8%), G. m. morsitans (23.4%), and G.pallidipes
(5.8%). All species showed monthly changes in abundance with most of the flies
collected in July. The relative abundance of G. m. morsitans and G. swynnertoni
was negatively correlated with maximum and minimum temperature, respectively.
Three trypanosome species were recorded: T. vivax (82.1%), T. brucei (8.93%), and
T. congolense (3.57%). The peak of trypanosome infections in the flies was found
in October and was three months after the tsetse abundance peak; prevalence was
negatively correlated with tsetse abundance. A strong positive relationship was
found between trypanosome prevalence and temperature. In conclusion, we find that
trypanosome prevalence is dependent on fly availability, and temperature drives
both tsetse fly relative abundance and trypanosome prevalence.
PMID- 28504438
TI - Aedes aegypti (L.) mosquitoes in Trinidad, West Indies: longevity case studies.
AB - Few laboratory and field studies have reported long survival periods for Ae.
aegypti females and even fewer have designed experiments to characterize this
important life history trait. This study was conducted under laboratory
conditions to determine the number of blood meals taken by individual females,
the number of eggs laid per individual female, the length of the gonotrophic
cycle, and the duration of female survival. The results showed individual females
oviposited between 670 and 1,500 eggs throughout their lifetimes, females
undergoing large numbers of gonotrophic cycles and surviving up to 224 days.
These results are discussed in the context of vector competence, unique
alternating high and low oviposition patterns observed after week 14, and
resource partitioning/allocation by older Ae. aegypti females after blood
feeding.
PMID- 28504440
TI - Corrigendum to: DNA-based identification and OspC serotyping in cultures of
Borrelia burgdorferi s.l. isolated from ticks collected in the Moravia (Czech
Republic).
PMID- 28504439
TI - Anaplasma phagocytophilum, Babesia microti, Borrelia burgdorferi sensu lato, and
Toxoplasma gondii in Ixodes ricinus (Acari, Ixodida) ticks collected from
Slowinski National Park (Northern Poland).
PMID- 28504442
TI - Involvement of invasive eastern red cedar (Juniperus virginiana) in the expansion
of Amblyomma americanum in Oklahoma.
PMID- 28504441
TI - Vector bionomics and malaria transmission along the Thailand-Myanmar border: a
baseline entomological survey.
AB - Baseline entomological surveys were conducted in four sentinel sites along the
Thailand-Myanmar border to address vector bionomics and malaria transmission in
the context of a study on malaria elimination. Adult Anopheles mosquitoes were
collected using human-landing catch and cow-bait collection in four villages
during the rainy season from May-June, 2013. Mosquitoes were identified to
species level by morphological characters and by AS-PCR. Sporozoite indexes were
determined on head/thoraces of primary and secondary malaria vectors using real
time PCR. A total of 4,301 anopheles belonging to 12 anopheline taxa were
identified. Anopheles minimus represented >98% of the Minimus Complex members
(n=1,683), whereas the An. maculatus group was composed of two dominant species,
An. sawadwongporni and An. maculatus. Overall, 25 Plasmodium-positive mosquitoes
(of 2,323) were found, representing a sporozoite index of 1.1% [95%CI 0.66-1.50].
The transmission intensity as measured by the EIR strongly varied according to
the village (ANOVA, F=17.67, df=3, P<0.0001). Our findings highlight the
diversity and complexity of the biting pattern of malaria vectors along the
Thailand-Myanmar border that represent a formidable challenge for malaria control
and elimination.
PMID- 28504443
TI - Bat ectoparasites (Nycteribiidae, Streblidae, Siphonaptera, Heteroptera,
Mesostigmata, Argasidae, and Ixodidae) from Algeria.
AB - Twenty two species of ectoparasites (Family Nycteribiidae: Nycteribia
(Listropoda) schmidlii schmidlii, Nycteribia (Nycteribia) latreillii, Nycteribia
(Nycteribia) pedicularia, Penicillidia (Penicillidia) dufourii, and Phthiridium
biarticulatum; Family Streblidae: Brachytarsina (Brachytarsina) flavipennis and
Raymondia huberi; Order Siphonaptera: Rhinolophopsylla unipectinata arabs,
Nycteridopsylla longiceps, Araeopsylla gestroi, Ischnopsyllus intermedius, and
Ischnopsyllus octactenus; Order Heteroptera: Cimex pipistrelli, Cimex
lectularius, and Cacodmus vicinus; Class Arachnida: Order Mesostigmata:
Spinturnix myoti and Eyndhovenia euryalis; Order Ixodida: Family Argasidae: Argas
transgariepinus and Argas vespertilionis; Family Ixodidae: Hyalomma dromedarii,
Ixodes ricinus, and Ixodes vespertilionis) were recovered from 19 bat species in
Algeria. New host records for bats are recorded for the first time: N. schmidlii
from Rh. clivosus and R. cystops; N. latreillii from Rh. blasii and P. gaisleri;
R. huberi from Rh. clivosus; C. pipistrelli from E. isabellinus and H. savii; C.
vicinus from E. isabellinus; S. myoti from P. gaisleri; E. euryalis from P.
gaisleri and Rh. blasii; A. vespertilionis from P. gaisleri; I. ricinus from T.
teniotis and Rh. hipposideros and H. dromedarii from P. kuhlii. Raymondia huberi
is recorded for the first time from Algeria.
PMID- 28504444
TI - Diversity, ecology, and seasonality of sand flies (Diptera: Psychodidae) of the
Jenin District (Palestinian Territories).
AB - The diversity, ecology, and seasonality for sand flies from two localities in
Jenin District, the Palestinian Territories, were studied. A total of 12,579 sand
flies (5,420 Phlebotomus and 7,159 Sergentomyia) were collected during the study
period. The genera Phlebotomus and Sergentomyia are represented by 13 and nine
species and subspecies, respectively. Species account was given for all collected
species. CDC light traps yielded 7,649 (60.8%) of the total captured sand flies,
while sticky traps and aspirators contributed to 36.4 and 2.8% of the total
collected specimens, respectively. Phlebotomus sergenti and P. syriacus showed
two peaks, one in July and one in October. Phlebotomus tobbi showed one peak
towards the end of the summer in September and August, while P. papatasi showed a
bimodal peaks pattern, one in June and one in October. Phlebotomus canaaniticus
showed a peak in August. P. perfiliewi transcaucasicus and P. neglectus showed a
peak in October. Sergentomyia dentata showed one peak in August and increasing
numbers from June to August, declining afterwards. Other species, such as S.
theodori, had one peak in June, S. taizi had steady numbers across the summer,
and S. christophersi had a peak in August.
PMID- 28504445
TI - First record of Anopheles daciae (Linton, Nicolescu & Harbach, 2004) in Poland.
PMID- 28504446
TI - Effects of a larval mosquito biopesticide and Culex larvae on a freshwater
nanophytoplankton (Selenastrum capricornatum) under axenic conditions.
AB - The effects of microbial biopesticides used for mosquito control on autotrophic
microorganisms such as nanophytoplankton are equivocal. We examined impacts of
mosquito biopesticides and mosquito larvae on primary producers in two
independent experiments. In the first experiment, we examined the effects of a
commonly used microbial biopesticide formulation (VectoMax(r) CG) on a
unicellular microalga, Selenastrum capricornatum Printz, under axenic laboratory
conditions. The biopesticide treatments included two concentrations (0.008 and
0.016 g liter-1 ) of VectoMax(r) CG and two controls (one untreated and another
with autoclaved 0.016 g VectoMax(r) CG liter-1 ) in replicated axenic
experimental microcosms. Spectrophotometric analysis of chlorophyll a (proxy for
algal biomass) and direct enumeration of algal cells following the treatments
revealed no significant effects of the microbial biopesticide on algal population
growth during the four-week study. In the second experiment, we tested the
effects of different densities of Culex larvae on the population of S.
capricornatum. Effects of mosquito larvae feeding on S. capricornatum were
significant with a curvilinear relationship between larval density and algal
abundance in the water column. Together, these studies demonstrated a lack of
direct cytological/toxicological effects of Bacillus-based microbial pesticides
on freshwater primary production and support the hypothesis that the reduction in
algal primary production previously reported when Bti products were applied to
aquatic environments was likely independent of the Bacillus-based larvicidal
toxins. Instead, it was likely mediated by microbial interactions in the water
column and the trophic cascade effects that resulted from the removal of larval
mosquitoes. These studies suggest that mosquito larvae independent of pesticide
application can influence primary production. Our method of evaluating
biopesticides against small photoautotrophs can be very useful for studying the
unintended effects on autotrophic microorganisms of other pesticides, including
herbicides and pesticides applied to aquatic environments.
PMID- 28504447
TI - Tick infestation of small mammals in an English woodland.
AB - Tick infestations on small mammals were studied from April to November, 2010, in
deciduous woodland in southern England in order to determine whether co
infestations with tick stages occurred on small mammals, a key requirement for
endemic transmission of tick-borne encephalitis virus (TBEV). A total of 217
small mammals was trapped over 1,760 trap nights. Yellow-necked mice (Apodemus
flavicollis) made up the majority (52.5%) of animals, followed by wood mice (A.
sylvaticus) 35.5% and bank voles (Myodes glareolus) 12%. A total of 970 ticks was
collected from 169 infested animals; 96% of ticks were Ixodes ricinus and 3% I.
trianguliceps. Over 98% of ticks were larval stages. Mean infestation intensities
of I. ricinus were significantly higher on A. flavicollis (6.53 +/- 0.67) than on
A. sylvaticus (4.96 +/- 0.92) and M. glareolus (3.25 +/- 0.53). Infestations with
I. ricinus were significantly higher in August than in any other month. Co
infestations with I. ricinus nymphs and larvae were observed on six (3.6%)
infested individuals, and fifteen small mammals (8.9%) supported I. ricinus - I.
trianguliceps co-infestations. This work contributes further to our understanding
of European small mammal hosts that maintain tick populations and their
associated pathogens, and indicates that co-infestation of larvae and nymph ticks
does occur in lowland UK. The possible implications for transmission of tick
borne encephalitis virus between UK ticks and small mammals are discussed.
PMID- 28504448
TI - Efficacy of a fipronil bait in reducing the number of fleas (Oropsylla spp.)
infesting wild black-tailed prairie dogs.
AB - Bubonic plague (Yersinia pestis) is a deadly zoonosis with black-tailed prairie
dogs (Cynomys ludovicianus) as a reservoir host in the United States. Systemic
insecticides are a promising means of controlling the vectors, Oropsylla spp.
fleas, infesting these prairie dogs, subsequently disrupting the Y. pestis cycle.
The objective of this study was to conduct a field trial evaluating the efficacy
of a grain rodent bait containing fipronil (0.005%) against fleas infesting
prairie dogs. The study was performed in Larimer County, CO, where bait was
applied to a treatment area containing a dense prairie dog population, three
times over a three-week period. Prairie dogs were captured and combed for fleas
during four study periods (pre-, mid-, 1st post-, and 2nd post-treatment).
Results indicated the use of bait containing fipronil significantly reduced flea
burden. The bait containing fipronil was determined to reduce the mean number of
fleas per prairie dog >95% for a minimum of 52 days post-initial treatment
application and 31 days post-final treatment application. These results suggest
the potential for this form of treatment to reduce flea population density on
prairie dogs, and subsequently plague transmission, among mammalian hosts across
the United States and beyond.
PMID- 28504449
TI - A decade of colonization: the spread of the Asian tiger mosquito in Pennsylvania
and implications for disease risk.
AB - In recent decades, the Asian tiger mosquito expanded its geographic range
throughout the northeastern United States, including Pennsylvania. The
establishment of Aedes albopictus in novel areas raises significant public health
concerns, since this species is a highly competent vector of several arboviruses,
including chikungunya, West Nile, and dengue. In this study, we used geographic
information systems (GIS) to examine a decade of colonization by Ae. albopictus
throughout Pennsylvania between 2001 and 2010. We examined the spatial and
temporal distribution of Ae. albopictus using spatial statistical analysis and
examined the risk of dengue virus transmission using a model that captures the
probability of transmission. Our findings show that since 2001, the Ae.
albopictus population in Pennsylvania has increased, becoming established and
expanding in range throughout much of the state. Since 2010, imported cases of
dengue fever have been recorded in Pennsylvania. Imported cases of dengue, in
combination with summer temperatures conducive for virus transmission, raise the
risk of local disease transmission.
PMID- 28504450
TI - The influence of environmental management and animal shelters in vector control
of Culicoides (Diptera, Ceratopogonidae) in northeastern Brazil.
AB - We investigated whether biting midges in peridomestic environments are affected
by environmental management practices and the presence of domestic animals. We
used CDC light traps to collect midges in 112 residences across 24 locations
along tourism routes of Maranhao, Brazil. The collection areas were characterized
as follows: i) peridomestic area with domestic animals and without management
(dirty); ii) peridomestic with domestic animals and management (clean); iii)
peridomestic without animals and with management (clean); iv) peridomestic
without animals and without management (dirty). The first two treatments had
higher biting midge species richness and abundance, respectively. Generalized
linear models indicated a positive correlation between the presence of domestic
animals and midge abundance, with an approximate four-fold increase in Culicoides
(Diptera: Ceratopogonidae) abundance in peridomestic areas with animals. The same
model showed that domestic animals have no influence on richness. Environmental
management does not appear to influence species richness or abundance of biting
midges.
PMID- 28504451
TI - Biological parameters of interbreeding populations of Meccus phyllosomus
longipennis (Usinger), 1939 (Hemiptera: Reduviidae: Triatominae) in Mexico.
PMID- 28504452
TI - Effect of CO2 concentration on mosquito collection rate using odor-baited suction
traps.
AB - Carbon dioxide (CO2 ) has been used for decades to enhance capture of host
seeking mosquitoes when released in association with traps commonly used by
mosquito and vector control agencies. However, there is little published work
evaluating the effect of altering CO2 release rates relative to the number of
mosquitoes captured in these traps. This study investigated how varying CO2
concentration altered the mosquito collection rate at a freshwater wetlands in
southern California. Host-seeking mosquitoes were captured in CDC-style traps
baited with one of six CO2 release rates ranging from 0-1,495 ml/min from gas
cylinders. Species captured were Aedes vexans, Anopheles franciscanus, An.
hermsi, Culex erythrothorax, and Cx. tarsalis. A biting midge, Culicoides
sonorensis, was also captured. For all species, increasing CO2 release rates
resulted in increasing numbers of individual females captured, with the relative
magnitude of this increase associated to some extent with known feeding
preferences of these species. We found that variation in CO2 release rate can
significantly alter mosquito capture rates, potentially leading to imprecise
estimates of vector activity if the relationship of CO2 release rate to mosquito
capture rate is not considered.
PMID- 28504453
TI - Reduced productivity of Culex pipiens and Cx. restuans (Diptera: Culicidae)
mosquitoes in parking area catch basins in the northeast Chicago metropolitan
area.
AB - From June to September, 2016, 100 catch basins in eight parking areas were
monitored weekly for the presence of mosquito pupae in the operational area of
the North Shore Mosquito Abatement District (NSMAD) located just north of
Chicago, IL, U.S.A. Weekly results from these basins were compared to weekly
samples taken from residential street catch basins, the most common type of catch
basin treated seasonally by the NSMAD with larvicides. Over the 17 study weeks,
residential street basins had a mean rate of productivity (pupae per basin-visit)
12 times that of parking area catch basins. The two parking area sites with the
highest mean rate of productivity were associated with county forest preserves.
Productivity in both street and parking area basins was positively associated
with the presence of three or more deciduous trees within 20 m of basins and if
they were located directly adjacent to curbs. Alternatively, productivity was
negatively associated with the proportion of impervious surface within 10 m of
basins and weekly rainfall. Findings suggest that reduced catch basin larvicide
applications may be appropriate in many parking area sites.
PMID- 28504454
TI - Ruthenium Complexes with Strongly Electron-Donating Terpyridine Ligands: Effect
of the Working Electrode on Electrochemical and Spectroelectrochemical
Properties.
AB - The combination of 2,2':6',2''-terpyridines (tpy) and RuII is known to deliver
molecular and supramolecular assemblies with remarkable properties. Here new RuII
complexes, with modified tpy ligands substituted with varying numbers of
dimethlyamino groups, are presented. Electrochemistry shows that the
incorporation of the strongly electron-donating groups on the tpy ligands leads
to a negative shift of the RuII oxidation potential by close to 1 V. The
reductive electrochemical responses are strongly dependent on the nature of the
working electrode, with glassy carbon and gold working electrodes showing the
best results. These observations led to the development of a modified Optically
Transparent Thin Layer Electrochemical (OTTLE) cell, based on a gold working
electrode. The use of UV/Vis/NIR spectroelectrochemical methods with that OTTLE
cell, together with simulations of the cyclic voltammograms, allowed the
characterization of four reduction steps in these complexes, the final two of
which lead to bond activations at the ruthenium center. This observation is to
the best of our knowledge unprecedented in coordinatively saturated complexes of
type [Ru(tpy)2 ]2+ . The various redox states of the complexes were characterized
by EPR spectroelectrochemistry and through DFT calculations. The results
presented here establish these substituted tpy ligands as highly attractive
ligands in coordination chemistry, and display the utility of a gold-based OTTLE
cell for spectroelectrochemical measurements.
PMID- 28504455
TI - Mycoplasma bovis isolates from dairy calves in Japan have less susceptibility
than a reference strain to all approved macrolides associated with a point
mutation (G748A) combined with multiple species-specific nucleotide alterations
in 23S rRNA.
AB - Erythromycin, tylosin and tilmicosin are approved for use in cattle in Japan, the
latter two being used to treat Mycoplasma bovis infection. In this study, 58 M.
bovis isolates obtained from Japanese dairy calves all exhibited reduced
susceptibility to these macrolides, this widespread reduced susceptibility being
attributable to a few dominant lineages. All 58 isolates contained the G748A
variant in both the rrl3 and rrl4 alleles of 23S rRNA, whereas a reference strain
(PG45) did not. G748 localizes in the central loop of domain II (from C744 to
A753) of 23S rRNA, which participates in binding to mycinose, a sugar residue
present in both tylosin and tilmicosin. A number of in vitro-selected mutants
derived from M. bovis PG45 showed reduced susceptibility to tylosin and
tilmicosin and contained a nucleotide insertion within the central loop of domain
II of rrl3 (U747-G748Ins_CU/GU or A743-U744Ins_UA), suggesting that mutations
around G748 confer this reduced susceptibility phenotype. However, other
Mycoplasma species containing G748A were susceptible to tylosin and tilmicosin.
Sequence comparison with Escherichia coli revealed that M. bovis PG45 and
isolates harbored five nucleotide alterations (U744C, G745A, U746C, A752C and
A753G) in the central loop of domain II of 23S rRNA, whereas other Mycoplasma
species lacked at least two of these five nucleotide alterations. It was
therefore concluded that G748 mutations in combination with species-specific
nucleotide alterations in the central loop of domain II of 23S rRNA are likely
sufficient to reduce susceptibility of M. bovis to tylosin and tilmicosin.
PMID- 28504457
TI - Electronic cigarettes, quit attempts and smoking cessation: a 6-month follow-up.
AB - BACKGROUND AND AIMS: There is conflicting evidence that use of e-cigarettes
promotes cessation in regular smokers, but contrasting findings may be due to
differing definitions of vaping. The aim was to assess whether regular use of e
cigarettes while smoking is associated with subsequent smoking cessation. DESIGN:
Baseline internet survey with outcomes measured at 6-month follow-up. SETTING:
All French metropolitan territory. PARTICIPANTS: A total of 2057 smokers aged 15
85 years were recruited through an access panel and responded to a 6-month follow
up: 1805 exclusive tobacco smokers and 252 dual users (tobacco plus regular e
cigarette users) at baseline. MEASUREMENTS: The three outcomes assessed at 6
months were: a minimum 50% reduction in the number of cigarettes smoked per day,
quit attempts of at least 7 days and smoking cessation of at least 7 days at the
time of follow-up. Logistic regressions were performed to model the three
outcomes according to regular e-cigarette use at baseline, adjusted for socio
economic variables and smoking behaviours. FINDINGS: Baseline dual users were
more likely than baseline exclusive tobacco smokers to have halved cigarette
consumption [25.9 versus 11.2%, P < 0.001, adjusted odds ratio (aOR) = 2.6,
confidence interval (CI) = 1.8-3.8]. Dual users at baseline were also more likely
to have made a quit attempt of at least 7 days (22.8 versus 10.9%, P < 0.001, aOR
= 1.8, CI = 1.2-2.6). No significant difference was found for 7-day cessation
rates at 6 months (12.5 versus 9.5%, P = 0.18, aOR = 1.2, CI = 0.8-1.9).
CONCLUSIONS: Among people who smoke, those also using an e-cigarette regularly
are more likely to try to quit smoking and reduce their cigarette consumption
during the next 6 months. It remains unclear whether regular e-cigarette users
are also more likely to stop smoking.
PMID- 28504458
TI - The burden of diabetes self-management in children and young adults.
PMID- 28504456
TI - Performance of mycology and histopathology tests for the diagnosis of toenail
onychomycosis due to filamentous fungi: Dermatophyte and non-dermatophyte moulds.
AB - Improvement of laboratory diagnosis of onychomychosis is important so that
adequate treatment can be safely implemented. To evaluate and compare the
performance of mycological and histopathological examinations in onychomycoses
caused by dermatophyte and non-dermatophyte moulds. Patients with lateral/distal
subungual onychomycosis in at least one hallux were enrolled in the protocol and
assessed via mycological and histopathological tests. The isolation of
filamentous fungi was considered the gold standard. Test performance was
evaluated through sensitivity, specificity and positive and negative predictive
values. A total of 212 patients were enrolled in the study. Direct microscopy
(DM) was positive in 57.5% patients, and cultures in 34.4%. Among these patients,
23.3% were positive for dermatophytes, with Trichophyton rubrum the most
frequently isolated, and 86.3% were positive for non-dermatophytes, with
Neoscytalidium dimidiatum predominance. Histopathology was positive in 41.0%
samples. Direct microscopy showed better sensitivity for non-dermatophyte moulds
(P=.000) and nail clipping was more specific for dermatophyte (P=.018).
Histopathology of the distal nail plate is a valuable complementary tool for the
diagnosis of onychomycosis caused by dermatophytes and direct microscopy is
especially useful for non-dermatophyte molds.
PMID- 28504460
TI - The cyclin dependent kinase subunit Cks1 is required for infection-associated
development of the rice blast fungus Magnaporthe oryzae.
AB - Cell cycle regulation is pivotal for proper cell division and cellular
differentiation in eukaryotic cells. The central regulators that govern
eukaryotic cell cycle progression are cyclin-dependent kinases (CDKs) and their
partners. Here, we report that Magnaporthe oryzae CKS1 encodes a cyclin-dependent
kinase subunit, which plays a significant role in regulation of plant infection.
We demonstrate that CKS1 is a functional homolog of CKS1/SUC1 and can physically
interact with the CDK protein Cdc28, and Som1, a downstream regulator of the
cyclic AMP-dependent Protein Kinase A pathway. CKS1 deletion mutants are severely
impaired in hyphal growth, sexual reproduction, melanin pigmentation and
conidiogenesis. Cks1 mutants are able to form appressoria from hyphal tips, but
these are unable to re-polarize, and rice infection is impaired. CKS1 also
affects chitin and glucan synthase activity during cell wall differentiation and
fungal hydrophobin function. CKS1, therefore, encodes a conserved CDK-binding
partner, essential for appressorium-mediated plant infection by the rice blast
fungus.
PMID- 28504461
TI - Ocular and nasal symptoms prior to acute skin graft-versus-host disease.
PMID- 28504459
TI - Steatosis caused by experimental periodontitis is reversible after removal of
ligature in rats.
AB - BACKGROUND AND OBJECTIVE: Periodontitis may promote harmful systemic effects such
as changes in hepatic tissues. The purpose of this study was to investigate
whether the steatosis and oxidative stress caused by experimental periodontitis
are reversible in the liver. MATERIAL AND METHODS: Twenty-four rats were divided
into three groups: control, periodontitis and P20-20 (20 days with experimental
periodontitis and 20 days without experimental periodontitis, to verify the
reversibility of hepatic injuries). The following parameters were assessed:
gingival bleeding index, probing pocket depth, myeloperoxidase activity, alveolar
bone loss for periodontal tissues; liver weights, histopathological scores for
steatosis, inflammation and necrosis in liver; glutathione, malondialdehyde,
total cholesterol and triglyceride concentrations in hepatic tissues; and blood
levels of aspartate aminotransferase, alanine aminotransferase, albumin, gamma
glutaryl transferase, total cholesterol and random glucose. RESULTS: Gingival
bleeding index, probing pocket depth, myeloperoxidase and alveolar bone loss
parameters demonstrated the development of periodontitis. There was a significant
reduction in the steatosis score of animals from the P20-20 group when compared
with the periodontitis group. P20-20 group presented significantly higher
glutathione (11 times) and lower malondialdehyde (nearly 23%), total cholesterol
(both in blood and hepatic tissue) and triglyceride concentrations compared with
the periodontitis group. For levels of aspartate aminotransferase, alanine
aminotransferase, albumin, gamma-glutaryl transferase and random glucose, a
significant difference between the groups was not observed. CONCLUSION: Our
results demonstrate that the microvesicular steatosis caused by periodontitis in
rats is reversible after removal of the ligature, which is associated with the
increase in oxidative stress and lipid peroxidation in the liver.
PMID- 28504463
TI - Magnetocatalytic Graphene Quantum Dots Janus Micromotors for Bacterial Endotoxin
Detection.
AB - Magnetocatalytic hybrid Janus micromotors encapsulating phenylboronic acid (PABA)
modified graphene quantum dots (GQDs) are described herein as ultrafast sensors
for the detection of deadly bacteria endotoxins. A bottom-up approach was adopted
to synthesize an oil-in-water emulsion containing the GQDs along with a high
loading of platinum and iron oxide nanoparticles on one side of the Janus
micromotor body. The two different "active regions" enable highly efficient
propulsion in the presence of hydrogen peroxide or magnetic actuation without the
addition of a chemical fuel. Fluorescence quenching was observed upon the
interaction of GQDs with the target endotoxin (LPS), whereby the PABA tags acted
as highly specific recognition receptors of the LPS core polysaccharide region.
Such adaptive hybrid operation and highly specific detection hold considerable
promise for diverse clinical, agrofood, and biological applications and
integration in future lab-on-chip technology.
PMID- 28504462
TI - Endocytic activity of HIV-1 Vpu: Phosphoserine-dependent interactions with
clathrin adaptors.
AB - HIV-1 Vpu modulates cellular transmembrane proteins to optimize viral replication
and provide immune-evasion, triggering ubiquitin-mediated degradation of some
targets but also modulating endosomal trafficking to deplete them from the plasma
membrane. Interactions between Vpu and the heterotetrameric clathrin adaptor
protein (AP) complexes AP-1 and AP-2 have been described, yet the molecular basis
and functional roles of such interactions are incompletely defined. To
investigate the trafficking signals encoded by Vpu, we fused the cytoplasmic
domain (CD) of Vpu to the extracellular and transmembrane domains of the CD8
alpha-chain. CD8-VpuCD was rapidly endocytosed in a clathrin- and AP-2-dependent
manner. Multiple determinants within the Vpu CD contributed to endocytic
activity, including phosphoserines of the beta-TrCP binding site and a leucine
based ExxxLV motif. Using recombinant proteins, we confirmed ExxxLV-dependent
binding of the Vpu CD to the alpha/sigma2 subunit hemicomplex of AP-2 and showed
that this is enhanced by serine-phosphorylation. Remarkably, the Vpu CD also
bound directly to the medium (MU) subunits of AP-2 and AP-1; this interaction was
dependent on serine-phosphorylation of Vpu and on basic residues in the MU
subunits. We propose that the flexibility with which Vpu binds AP complexes
broadens the range of cellular targets that it can misdirect to the virus'
advantage.
PMID- 28504464
TI - Skeletal maturity of the hand in an East African group from Sudan.
AB - OBJECTIVES: Studies of skeletal maturity from Africa indicate a delay, reflected
in a negative relative skeletal age (RSA). This study aims to evaluate the
influence of age, socioeconomic status (SES) and nutritional status on skeletal
maturation in a large sample of children from North Sudan. MATERIALS: The sample
consisted 665 males and 1018 females from 3-25 years from Khartoum. Height,
weight, age of menarche and, SES were recorded of patients attending for dental
treatment. METHODS: Skeletal age was assigned from hand-wrist radiographs using
the Greulich-Pyle (GP) atlas (1952). RSA (difference between skeletal and
chronological ages) was compared in groups divided by age, sex, height-for-age
and body-mass-index z scores, and SES. Spearman's correlation and student t-test
was used to compare groups. RESULTS: Delayed skeletal age was noted across all
age in boys. In girls, a delay was observed between ages 6-10, while advancement
occurred between ages 13-18. Maturity was delayed in low height groups (p < .05)
and low SES groups. RSA was negatively associated with HAZ in low SES males (R =
0.0.27, p < .001) and low SES females (R = -0.32, p < .001). CONCLUSIONS: There
were statistically significant skeletal delays in North Sudanese males and most
pre-menarche females, low height and low SES groups. Post-menarche females were
advanced relative to males and GP references. Low SES impacts were statistically
correlated to skeletal delay.
PMID- 28504465
TI - Effects of SA237, a humanized anti-interleukin-6 receptor monoclonal antibody, on
pre- and postnatal development in cynomolgus monkey.
AB - BACKGROUND: SA237 is a humanized anti-interleukin-6 receptor (IL-6R) monoclonal
antibody in which the constant and variable regions have been engineered for a
longer plasma half-life. According to literature, blocking of IL-6 related
functions could have an influence on pregnancy sustainment, development of the
immune system, and brain growth. METHODS: SA237 effects on dams, embryo-fetal
development, parturition and postnatal development were investigated in an
enhanced pre- and postnatal development study, in which SA237 was subcutaneously
administered to pregnant cynomolgus monkeys at dose levels of 2 or 50 mg/kg once
weekly from gestation day 20 until parturition. Infant development, including
immune function and learning ability tests, was comprehensively assessed at
multiple examinations until approximately 10 months after birth. RESULTS: SA237
plasma concentrations were almost equivalent between dams and their infants and
dropped throughout the postnatal period, pharmacologically relevant exposure was
maintained for 147 days after birth at 50 mg/kg. Because the binding of SA237 to
IL-6R inhibited IL-6R-mediated clearance of IL-6, serum IL-6 increased in dams
and infants. However, there were no SA237-related adverse effects on dams,
embryos, fetuses, or infants. SA237 pharmacological effects contributed to the
suppression of plasma cell differentiation and antibody production by inhibiting
IL-6 signaling, and T cell-dependent antibody reaction was minimally suppressed
in infants, but physiological immunoglobulin class switching and general antibody
production against a T cell-dependent antigen were maintained. CONCLUSION: The
exposure to SA237 did not adversely affect dams, embryo-fetal development,
parturition, and postnatal development, including immune function and neuronal
development. Birth Defects Research 109:843-856, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28504467
TI - Corona[5]arenes Accessed by a Macrocycle-to-Macrocycle Transformation Route and a
One-Pot Three-Component Reaction.
AB - Corona[5]arenes, a novel type of macrocyclic compound that is composed of
alternating heteroatoms and para-arylenes, were synthesized efficiently by two
distinct methods. In a macrocycle-to-macrocycle transformation approach, S6
corona[3]arene[3]tetrazine underwent sequential SN Ar reactions with HS-C6 H4 -X
C6 H4 -SH (X=S, CH2 , CMe2 , SO2 , and O) to produce the corresponding
corona[3]arene[2]tetrazines. Different corona[3]arene[2]tetrazine compounds were
also constructed in a straightforward manner by a one-pot three-component
reaction of HS-C6 H4 -X-C6 H4 -SH (X=S, CH2 , CMe2 , SO2 , and O) with diethyl
2,5-dimercaptoterephthalate and 2 equiv of 3,6-dichlorotetrazine under very mild
conditions. All corona[5]arenes adopted 1,2,4-alternate conformational structures
in the crystalline state yielding similar nearly regular pentagonal cavities.
Both the cavity size and the electronic property of the acquired macrocycles were
fine-tuned by the nature of the bridging element X.
PMID- 28504466
TI - Nepetoidin B, a Natural Product, Inhibits LPS-stimulated Nitric Oxide Production
via Modulation of iNOS Mediated by NF-kappaB/MKP-5 Pathways.
AB - Previous reports showed that nepetoidin B (NTB), a natural product isolated from
many herbs, has anti-fungal and anti-bacterial effects. In this study, the
antiinflammatory effect of NTB was investigated in lipopolysaccharide (LPS)
stimulated RAW 264.7 macrophages. The cytotoxic effect of NTB and LPS was
determined by MTT assay. The nitric oxide (NO) production was detected by Griess
assay. The TNF-alpha and IL-6 levels were determined by enzyme-linked
immunosorbent assay kits. Protein expressions were tested by western blotting.
The transcription activity of inducible nitric oxide synthase (iNOS) was detected
by luciferase assay. Immunofluorescence assay was used to observe the
visualization of NF-kappaB/p65 nuclear translocation. NTB and LPS showed no
obvious cytotoxic effect on RAW 264.7 cells. NTB remarkably inhibited LPS-induced
NO and TNF-alpha secretion in a concentration-dependent manner while showed no
significant effect on IL-6 secretion. NTB inhibited LPS-induced iNOS protein
expression and transcription activity without affecting cyclooxygenase-2.
Furthermore, NTB suppressed LPS-stimulated NF-kappaB/p65 phosphorylation and
nuclear translocation. In addition, NTB significantly inhibited LPS-induced
phosphorylation of JNK1/2 and p38MAPK without affecting ERK1/2. LPS-induced
inhibition of mitogen-activated protein kinase phosphatase-5 (MKP-5) was
completely reversed by NTB. In conclusion, these results suggested that NTB
inhibited LPS-stimulated NO production possibly via modulation of iNOS mediated
by MKP-5/NF-kappaB pathways in RAW 264.7 cells. Copyright (c) 2017 John Wiley &
Sons, Ltd.
PMID- 28504468
TI - Incubatory environment of the scalp impacts pre-emergent hair to affect post
emergent hair cuticle integrity.
AB - OBJECTIVES: To determine whether the oxidative stress transmitted to newly grown
hair from an unhealthy scalp has physical consequences to the cuticular condition
and function. METHODS: A uniquely designed 24-week clinical study included 8
weeks of pretreatment with a cosmetic shampoo and 16 weeks of treatment with
either a potentiated zinc pyrithione (ZPT) antidandruff shampoo or a placebo
cosmetic shampoo. This clinical design allowed the growth and acquisition of hair
samples under conditions of varying but known scalp health as a result of
treating a dandruff/seborrheic dermatitis (D/SD) population. Two complementary
methods were used to characterize the integrity of the cuticular surface. Hair
surface hydrophobicity was assessed by quantifying water wetting force using a
Wilhelmy balance method. Surface structure and porosity were assessed using
dynamic vapor sorption (DVS) to gravimetrically quantify water sorption. RESULTS:
Chemical oxidative stress to pre-emergent hair has been shown to have negative
consequences to hair surface structure. Compared to a placebo shampoo control,
use of a potentiated ZPT shampoo improved scalp health and significantly improved
the following attributes associated with healthy hair: hair surface
hydrophobicity (surface energy) and cuticular moisture barrier effectiveness
(dynamic vapor sorption). CONCLUSIONS: Pre-emergent hair can be negatively
impacted by the oxidative stress that occurs with an unhealthy scalp, possibly
due to metabolic activity of resident microbes. Manifestations of the oxidative
stress include altered cuticle surface properties that are responsible for its
protective function; these effects are similar in type to those observed by
bleaching post-emergent hair. These alterations have the potential to make the
hair, once emerged from the scalp, more susceptible to the cumulative physical
and chemical insults responsible for hair feel and look, fiber integrity, and
overall retention.
PMID- 28504469
TI - Subtle but ubiquitous selection on body size in a natural population of collared
flycatchers over 33 years.
AB - Understanding the magnitude and long-term patterns of selection in natural
populations is of importance, for example, when analysing the evolutionary impact
of climate change. We estimated univariate and multivariate directional,
quadratic and correlational selection on four morphological traits (adult wing,
tarsus and tail length, body mass) over a time period of 33 years (~ 19 000
observations) in a nest-box breeding population of collared flycatchers (Ficedula
albicollis). In general, selection was weak in both males and females over the
years regardless of fitness measure (fledged young, recruits and survival) with
only few cases with statistically significant selection. When data were analysed
in a multivariate context and as time series, a number of patterns emerged; there
was a consistent, but weak, selection for longer wings in both sexes, selection
was stronger on females when the number of fledged young was used as a fitness
measure, there were no indications of sexually antagonistic selection, and we
found a negative correlation between selection on tarsus and wing length in both
sexes but using different fitness measures. Uni- and multivariate selection
gradients were correlated only for wing length and mass. Multivariate selection
gradient vectors were longer than corresponding vector of univariate gradients
and had more constrained direction. Correlational selection had little
importance. Overall, the fitness surface was more or less flat with few cases of
significant curvature, indicating that the adaptive peak with regard to body size
in this species is broader than the phenotypic distribution, which has resulted
in weak estimates of selection.
PMID- 28504470
TI - Hemorrhagic fever with renal syndrome caused by Hantaan virus infection in four
pregnant Chinese women.
AB - Hantavirus infection during pregnancy can influence both maternal and fetal
outcomes. Here, we describe four cases of hemorrhagic fever with renal syndrome
(HFRS) in pregnant Chinese women. The HFRS put these women at increased risk for
severe illness, despite the patients' symptomologies in the onset phase were
similar to those observed in non-pregnant HFRS patients, such as fever, headache,
nausea, and thrombocytopenia. Pregnant women appeared to have a more severe
status, presenting with severe complications, such as hypervolemia and pulmonary
edema. Nevertheless, with appropriate management, mothers with HFRS may carry to
full-term and breastfeeding maybe safe and feasible.
PMID- 28504471
TI - Scedosporium apiospermum complex in cystic fibrosis; should we treat?
AB - Species of the Scedosporium apiospermum complex are the second most frequent
filamentous fungi after Aspergillus fumigatus that can be found in cystic
fibrosis (CF). Mixed colonisation by S. apiospermum complex and A. fumigatus is
also quite common. In this study we summarise all CF patients who were colonised
by S. apiospermum complex during their childhood and we present two CF patients
who were treated as fungal bronchitis due to S. apiospermum complex. The medical
records of 400 CF patients were reviewed in order to identify those with positive
respiratory cultures for S. apiospermum complex. Scedosporium apiospermum complex
was isolated in 10 CF patients and six of them had more than two positive sputum
cultures during the study period. By the time of first isolation, the median age
was 14.5 years, the median BMI was 19.41 kg/m2 , the median predicted FEV1 % was
78.65% and six patients had a history of A. fumigatus isolation. Two patients
presented symptoms of infection while they were colonised by S. apiospermum
complex. A rapid remission of their symptoms was observed only when antifungal
therapy was administered. Antifungal treatment should be considered in CF
patients who present symptoms of infection not responding to antibacterial
therapy and S. apiospermum complex is persistently growing in sputum cultures.
PMID- 28504472
TI - Thoughtflow: Standards and Tools for Provenance Capture and Workflow Definition
to Support Model-Informed Drug Discovery and Development.
AB - Pharmacometric analyses are complex and multifactorial. It is essential to check,
track, and document the vast amounts of data and metadata that are generated
during these analyses (and the relationships between them) in order to comply
with regulations, support quality control, auditing, and reporting. It is,
however, challenging, tedious, error-prone, and time-consuming, and diverts
pharmacometricians from the more useful business of doing science. Automating
this process would save time, reduce transcriptional errors, support the
retention and transfer of knowledge, encourage good practice, and help ensure
that pharmacometric analyses appropriately impact decisions. The ability to
document, communicate, and reconstruct a complete pharmacometric analysis using
an open standard would have considerable benefits. In this article, the
Innovative Medicines Initiative (IMI) Drug Disease Model Resources (DDMoRe)
consortium proposes a set of standards to facilitate the capture, storage, and
reporting of knowledge (including assumptions and decisions) in the context of
model-informed drug discovery and development (MID3), as well as to support
reproducibility: "Thoughtflow." A prototype software implementation is provided.
PMID- 28504473
TI - Dynamic Cooperative Glycan Assembly Blocks the Binding of Bacterial Lectins to
Epithelial Cells.
AB - Pathogens frequently rely on lectins for adhesion and cellular entry into the
host. Since these interactions typically result from multimeric binding of
lectins to cell-surface glycans, novel therapeutic strategies are being developed
with the use of glycomimetics as competitors of such interactions. Herein we
study the benefit of nucleic acid based oligomeric assemblies with PNA-fucose
conjugates. We demonstrate that the interactions of a lectin with epithelial
cells can be inhibited with conjugates that do not form stable assemblies in
solution but benefit from cooperativity between ligand-protein interactions and
PNA hybridization to achieve high affinity. A dynamic dimeric assembly fully
blocked the binding of the fucose-binding lectin BambL of Burkholderia ambifaria,
a pathogenic bacterium, to epithelial cells with an efficiency of more than 700
fold compared to l-fucose.
PMID- 28504474
TI - A Simple Post-Polymerization Modification Method for Controlling Side-Chain
Information in Digital Polymers.
AB - A three-step post-polymerization modification method was developed for the design
of digitally encoded poly(phosphodiester)s with controllable side groups.
Sequence-defined precursors were synthesized, either manually on polystyrene
resins or automatically on controlled pore glass supports, using two
phosphoramidite monomers containing either terminal alkynes or triisopropylsilyl
(TIPS) protected alkyne side groups. Afterwards, these polymers were modified by
stepwise copper-catalyzed azide-alkyne cycloaddition (CuAAC). The terminal
alkynes were first reacted with a model azide compound, and after removal of the
TIPS groups, the remaining alkynes were reacted with another organic azide. This
simple method allows for quantitative side-chain modification, thus opening up
interesting avenues for the preparation of a wide variety of digital polymers.
PMID- 28504475
TI - MAP3K1-related gonadal dysgenesis: Six new cases and review of the literature.
AB - Investigation of disorders of sex development (DSD) has resulted in the discovery
of multiple sex-determining genes. MAP3K1 encodes a signal transduction regulator
in the sex determination pathway and is emerging as one of the more common genes
responsible for 46,XY DSD presenting as complete or partial gonadal dysgenesis.
Clinical assessment, endocrine evaluation, and genetic analysis were performed in
six individuals from four unrelated families with 46,XY DSD. All six individuals
were found to have likely pathogenic MAP3K1 variants. Three of these individuals
presented with complete gonadal dysgenesis, characterized by bilateral streak
gonads with typical internal and external female genitalia, while the other three
presented with partial gonadal dysgenesis, characterized by incomplete testicular
development, resulting in clitoral hypertrophy with otherwise typical female
external genitalia. Testing for MAP3K1 variants should be considered in patients
with 46,XY complete or partial gonadal dysgenesis, particularly in families with
multiple members affected with 46,XY DSD. Identification of a MAP3K1 variant
should prompt an evaluation for DSD in female siblings of the proband.
PMID- 28504477
TI - Corrigendum.
PMID- 28504476
TI - Thirty years of interferon-tau research; Past, present and future perspective.
AB - The year 2017 marks the 30th year since the discovery was made of amino acid and
complementary DNA sequences of ovine trophoblast protein-1 (oTP-1), later renamed
as interferon-tau (IFNtau). Ovine TP-1 was originally found as a secretory
product of sheep conceptuses that rescues maternal corpus luteum (CL) and in
fact, the uterine infusion of oTP-1 extended inter-estrous intervals. Finding
this signaling molecule as an IFN-like sequence was surprising to the scientific
community in reproduction because a homologous molecule in humans possesses anti
viral and anti-prolific activity and is often used in human medicines. However,
since its discovery was made, large efforts have been made in the elucidation of
transcriptional regulation and functions of bovine and ovine IFNtaus, more
importantly, the improvement of pregnancy rates in sheep and cattle, most of
which resulted in unsuccessful outcomes. In this review, physiological, cellular
and molecular events associated with continued secretion of progesterone,
maternal recognition of pregnancy, identification, transcriptional regulation and
function of IFNtau, and its future perspectives will be discussed.
PMID- 28504478
TI - Reduced egg shell permeability affects embryonic development and hatchling traits
in Lycodon rufozonatum and Pelodiscus sinensis.
AB - The response of embryos to unpredictable hypoxia is critical for successful
embryonic development, yet there remain significant gaps in our understanding of
such responses in reptiles with different types of egg shell. We experimentally
generated external regional hypoxia by sealing either the upper half or bottom
half of the surface area of eggs in 2 species of reptiles (snake [Lycodon
rufozonatum] with parchment egg shell and Chinese soft-shelled turtle [Pelodiscus
sinensis] with rigid egg shell), then monitored the growth pattern of the opaque
white patch in turtle eggs (a membrane that attaches the embryo to the egg shell
and plays an important role in gas exchange), the embryonic heart rate, the
developmental rate and the hatchling traits in turtle and snake eggs in response
to external regional hypoxia. The snake embryos from the hypoxia treatments
facultatively increased their heart rate during incubation, and turtle embryos
from the upper-half hypoxia treatment enhanced their growth of the opaque white
patch. Furthermore, the incubation period and hatching success of embryos were
not affected by the hypoxia treatment in these 2 species. External regional
hypoxia significantly affected embryonic yolk utilization and offspring size in
the snake and turtle. Compared to sham controls, embryos from the upper-half
hypoxia treatment used less energy from yolk and, therefore, developed into
smaller hatchlings, but embryos from the bottom-half hypoxia treatment did not.
PMID- 28504479
TI - Contribution of anthocyanin-rich foods in obesity control through gut microbiota
interactions.
AB - Obesity is characterized by low-grade inflammation and a number of metabolic
disorders. Distal gut microbes' content (microbiota) is not yet fully understood
but evidence shows that it is influenced by internal and external factors that
modulate its composition and function. The evidence that gut microbiota
composition can differ between healthy and obese individuals, as well as for
those who maintain specific dietary habits, has led to the study of this
environmental factor as a key link between the pathophysiology of obesity and gut
microbiota. Data obtained about the role of anthocyanins (ACNs) in microbiota may
lead to different strategies to manipulate bacterial populations and promote
health. Anthocyanins have been identified as modulators of gut microbiota that
contribute to obesity control and these bioactive compounds should be considered
to have a prebiotic action. This review addresses the relevance of knowledge
about the influence of anthocyanins-rich food consumption on microbiota, and
their health-promoting potential in the pathophysiology of obesity. (c) 2017
BioFactors, 43(4):507-516, 2017.
PMID- 28504480
TI - Therapeutic effect of microneedling and autologous platelet-rich plasma in the
treatment of atrophic scars: A randomized study.
AB - BACKGROUND: New treatments and techniques were being added over the last few
years to treat atrophic scars with variable results and adverse effects. AIM OF
THE WORK: The aim of this study was to evaluate and compare the therapeutic
efficacy and safety of microneedling, autologous platelet-rich plasma, and
combination of both procedures in the treatment of atrophic scars. PATIENTS AND
METHODS: This study included 90 patients with atrophic scars and were classified
randomly into three groups: I: 28 patients treated with microneedling, one
session every 4 weeks; II: 34 patients treated with intradermal injection of
platelet-rich plasma, one session every 2 weeks; and III: 28 patients treated
with alternative sessions of each microneedling and platelet-rich plasma, 2 weeks
between each session, for a maximum of six sessions. RESULTS: There was a
statistically significant improvement in the appearance of atrophic scars, with
reduction in the scores associated with the clinical evaluation scale for
atrophic scarring in all groups, but the improvement was more obvious in group
III. CONCLUSIONS: Although a single treatment may give good results, combination
between skin needling and platelet-rich plasma is more effective, safe with less
number of sessions in all types of atrophic scars.
PMID- 28504481
TI - Comprehensive mass cytometry analysis of cell cycle, activation and co-inhibitory
receptors expression in CD4 T cells from healthy and HIV-infected individuals.
PMID- 28504482
TI - Asymmetric Copper-Catalyzed Carbomagnesiation of Cyclopropenes.
AB - The highly diastereo- and enantioselective formation of polysubstituted
cyclopropanes was easily achieved through the asymmetric copper-catalyzed
carbomagnesiation reaction of nonfunctionalized cyclopropene derivatives. The
carbometalated species generated in situ readily undergo C-C and C-X bond-forming
reactions with various electrophiles with complete retention of configuration.
PMID- 28504484
TI - Disclosing errors to patients and parents, and apologizing.
PMID- 28504483
TI - Comparison of a New Intranasal Naloxone Formulation to Intramuscular Naloxone:
Results from Hypothesis-generating Small Clinical Studies.
AB - Easy-to-use naloxone formulations are needed to help address the opioid overdose
epidemic. The pharmacokinetics of i.v., i.m., and a new i.n. naloxone formulation
(2 mg) were compared in six healthy volunteers. Relative to i.m. naloxone,
geometric mean (90% confidence interval [CI]) absolute bioavailability of i.n.
naloxone was modestly lower (55%; 90% CI, 43-70% vs. 41%; 90% CI, 27-62%),
whereas average (+/-SE) mean absorption time was substantially shorter (74 +/-
8.8 vs. 6.7 +/- 4.9 min). The opioid-attenuating effects of i.n. naloxone were
compared with i.m. naloxone (2 mg) after administration of oral alfentanil (4 mg)
to a separate group of six healthy volunteers pretreated with 240 mL of water or
grapefruit juice. The i.m. and i.n. naloxone attenuated miosis by similar extents
after water (40 +/- 15 vs. 41 +/- 21 h*%) and grapefruit juice (49 +/- 18 vs. 50
+/- 22 h*%) pretreatment. Results merit further testing of this new naloxone
formulation.
PMID- 28504485
TI - Emotional exhaustion is associated with work related stressors: a cross-sectional
multicenter study in Malaysian public hospitals.
AB - INTRODUCTION: Emotional exhaustion is an important component of burnout. Burnout
is common among doctors. It affects the physical and mental health of doctors,
their performance and the quality of care they provide. This study aimed to
investigate the level and factors associated with emotional exhaustion among
doctors in pediatric practice in Malaysia. POPULATION AND METHODS: A self
administered questionnaire was used in this multicenter cross-sectional study. It
included questions on the socio-demographics, work characteristics, Emotional
Exhaustion, Perceived Stress Scale and sources of job stress. Descriptive,
univariate and multivariate analysis were conducted using the SPSS software.
RESULTS: A total of 197 doctors working in the Pediatric department in eight
hospitals returned complete questionnaire. High and moderate emotional exhaustion
was reported by 25.4% and 24.4% doctors, respectively. In bivariate analysis, 29
out of the 38 items of sources of stress showed significant association with
emotional exhaustion (p <0.05).The significant predictors of emotional exhaustion
in the multivariate analysis were: scoring higher on the Perceived Stress Score,
dealing with patient's psychosocial problems, disrespectful interactions with
colleagues/ subordinates, lack of appreciation from supervisors, lack of
incentives and promotions, time pressures and deadlines to meet, and setting
unrealistic goals of having them imposed on oneself (p <0.05). The most common
source of stress was dealing with difficult parents (80.2%). CONCLUSIONS:
Emotional exhaustion is associated with sources of stress in the workplace but
not with socio-demographic factors.
PMID- 28504486
TI - High prevalence of vitamin D deficiency among children with chronic kidney
disease and kidney transplant.
AB - INTRODUCTION: Vitamin D (25(OH)D) deficiency is common among patients with
chronic kidney disease (CKD). Our objective was to establish the prevalence of
25(OH)D deficiency among children with CKD and identify risk factors. A
correlation was observed between 25(OH)D and parathormone intact molecule.
POPULATION AND METHODS: Cross-sectional study conducted between January 2013 and
December 2015. Patients younger than 19 years old with and without CKD were
included. RESULTS: One hundred and sixty-seven patients were included. Group 1
(healthy controls): 32 participants; group 2 (stage 2-4 CKD, glomerular
filtration rate between 89 and 15 mL/min/1.73 m2): 34 patients; group 3 (stage 5
CKD, dialysis): 46 patients; and group 4 (kidney transplant recipients): 55
patients. Deficiency of 25(OH)D was detected in 12.5% of healthy controls and 32%
of CKD patients (p= 0.025). Also, 23% of patients in group 2, 51% in group 3, and
22% in group 4 had 25(OH)D deficiency; the mean 25(OH)D level of dialysis
patients was significantly lower than that of the rest of the groups. Predictors
of 25(OH)D deficiency included hypoalbuminemia, advanced CKD, and place of origin
from the Northwest region of Argentina. The parathormone intact molecule was
significantly higher in the group of patients with deficiency and was inversely
correlated with 25(OH)D levels. CONCLUSION: Among CKD patients, 32% had 25(OH)D
deficiency, which reached 51% among those with stage 5 CKD (dialysis). Predictors
of deficiency included hypoalbuminemia, advanced CKD, and place of origin from
the Northwest region of Argentina.
PMID- 28504487
TI - Haemophilus influenzae type B meningitis: Is there a re-emergence? 24 years of
experience in a children's hospital.
AB - INTRODUCTION: Haemophilus influenzae type B (Hib) used to be the main cause of
bacterial meningitis in children younger than 5 years old. Following the
introduction of the Hib vaccine in the immunization schedule (1998), its
incidence reduced significantly but it has increased over the last years. The
objectives of this study included describing the characteristics and analyzing
the epidemic curve of Haemophilus influenzae type B (Hib) meningitis by comparing
the pre- and postimmunization periods. MATERIALS AND METHODS: Time-series study.
All patients hospitalized with Hib meningitis at Hospital de Ninos "R. Gutierrez"
(January 1992-May 2016). Hospitalization rates were compared before (pre
immunization) and after (post-immunization) the introduction of the Hib vaccine.
The post-immunization period was divided into three similar periods. RESULTS:
Eighty-five patients with Hib meningitis were admitted (73.3% in the pre
immunization period). No differences were observed in relation to the clinical
and sociodemographic characteristics of cases in both periods. Pre-immunization:
10.5 cases/year; postimmunization: 0.7 cases/year. As of 2014, the rate has
increased. Lethality rate: 4.8% (all preimmunization). Post-immunization data (n=
15): 40% had completed their primary immunization schedule, 40% were delayed on
the immunization schedule for their age. Overall reduction in the hospital rate
of Hib meningitis by 89.8% (95% confidence interval: -82.79-93.96%, p < 0.001) in
the post-immunization period. The analysis of the different post-immunization
periods shows a decline in reduction over time. CONCLUSIONS: A very significant
reduction in hospitalizations due to Hib meningitis was observed after the Hib
vaccine was introduced; however, over the past years, the number of cases has
increased although no changes have been observed in patient characteristics.
PMID- 28504488
TI - Argentine references for the assessment of body proportions from birth to 17
years of age.
AB - INTRODUCTION: Abnormal body proportions may indicate skeletal disorders;
therefore, their detection has great clinical significance. OBJETIVES: To
estimate centiles for head circumference/height (HC/H) and sitting height/height
(SH/H) ratios, and assess their diagnostic usefulness among a group of children
with skeletal dysplasia. METHODS: Centiles 3, 10, 25, 50, 75, 90 and 97 for HC/H
and SH/H ratios were estimated with the LMS method using Box-Cox transformation
to normalize data distribution for each age. Q-Q plot tests were applied to
evaluate normality of residuals and the Q test to calculate goodness-of-fit.
RESULTS: The sample included 4818 girls and4803 boys, all healthy, between 0-17
years old. The median of the SH/H ratio for each age decreased from 0.67 at birth
to 0.57 at age 4. At 12 years of age, values reached 0.52 and 0.53 for males and
females, respectively, remaining unchanged until age 17. The median of the HC/H
ratio decreased from 0.45 at 6 years old to 0.34 at 17 years old for both sexes.
Z-scores for SH/H among 20 children diagnosed with hypochondroplasia were better
at showing abnormal proportions than the SH/H ratio not adjusted by age.
CONCLUSIONS: Estimated centiles for HC/H and SH/H ratios show that the most
dramatic changes in body proportions occur in the prepubertal period. These
references allow an earlier detection of abnormal body proportions in children
with skeletal dysplasia.
PMID- 28504489
TI - Psychometric properties of scales used for grading the severity of bronchial
obstruction in pediatrics: A systematic review and meta-analysis.
AB - INTRODUCTION: In pediatrics, identifying the severity of bronchial obstruction in
an early manner is a decisive factor. OBJETIVE: To assess the psychometric
properties of the scales for grading the severity of bronchial obstruction in
pediatric patients. POPULATION AND METHOD: This was a systematic review of
studies on the validity and reliability of scales for grading the severity of
bronchial obstruction conducted in infants and children younger than 3 years old.
The search was conducted in Medline, WoS, EMBASE, SciELO, and Google Scholar. The
correlation coefficient corresponding to each article was included in a random
effects model to establish the criterion validity and reliability using the
weighted averages of coefficients as per the sample size. RESULTS: A total of 9
articles were included, which accounted for 2699 children; 3 articles had an
adequate or excellent methodological quality. Four articles established the
concurrent criterion validity considering oxygen saturation, with a weighted
correlation coefficient of -0.627 (95% confidence interval [CI]: -0.767 to
0.431, p < 0.001); 2 articles established the convergent criterion validity, with
a weighted correlation coefficient of 0.809 (95% CI: 0.721 to 0.871, p < 0.001);
6 articles established the inter-observer reliability, with a weighted
correlation coefficient of0.500for kappa and 0.891 for the intraclass correlation
coefficient. CONCLUSION: The assessment of psychometric properties to support the
use of scales for grading the construct "severity of bronchial obstruction"
showed a moderate to adequate criterion validity. The percentage of agreement
among observers in terms of the studied measure (severity of bronchial
obstruction) was adequate; however, weaknesses such as the article design should
be taken into account since it may affect the internal validity of results.
PMID- 28504490
TI - Additive effect of mesenchymal stem cells and defibrotide in an arterial rat
thrombosis model.
AB - BACKGROUND/AIM: In this study, we aimed to investigate the additive effect of
mesenchymal stem cells (MSC) and defibrotide (DFT) in a rat model of femoral
arterial thrombosis. METHODS: Thirty Sprague Dawley rats were included. An
arterial thrombosis model by ferric chloride (FeCl3) was developed in the left
femoral artery. The rats were equally assigned to 5 groups: Group 1-Sham-operated
(without arterial injury); Group 2-Phosphate buffered saline (PBS) injected;
Group 3-MSC; Group 4-DFT; Group 5-MSC + DFT. All had two intraperitoneal
injections of 0.5 ml: the 1st injection was 4 h after the procedure and the 2nd
one 48 h after the 1st injection. The rats were sacrificed 7 days after the 2nd
injection. RESULTS: Although the use of human bone marrow-derived (hBM) hBM-MSC
or DFT alone enabled partial resolution of the thrombus, combining them resulted
in near-complete resolution. Neovascularization was two-fold better in hBM-MSC +
DFT treated rats (11.6 +/- 2.4 channels) compared with the hBM-MSC (3.8 +/- 2.7
channels) and DFT groups (5.5 +/- 1.8 channels) (P < 0.0001 and P= 0.002,
respectively). CONCLUSION: The combined use of hBM-MSC and DFT in a rat model of
arterial thrombosis showed additive effect resulting in near-complete resolution
of the thrombus.
PMID- 28504491
TI - Profile of spontaneous demand for services among infants younger than 30 days old
at a children's tertiary care hospital.
AB - INTRODUCTION: In recent years, admission of critical newborn infants (NBIs) to
the neonatal intensive care unit of Hospital Garrahan (HG) has been limited due
to the hospitalization of infants younger than 30 days old through spontaneous
demand for services. This is probably a multifactorial situation, and one of its
causes is a lack of regionalization, which results in an inadequate use of
resources or a distorted use of resources intended for more complex care.
OBJECTIVE: To establish the profile of NBIs who make a spontaneous demand for
services at HG and to assess the level of care required based on their medical
condition. MATERIALS AND METHODS: Cross-sectional study. All infants < 30 days
old who sought care at HG in a period of 12 months were assessed. The analysis
included clinical characteristics of NBIs, prior visits, parental reason for
consultation at HG, and whether NBIs could have been seen at a primary or
secondary care facility. RESULTS: A total of 307 consultations were analyzed; NBI
age was 18 days +/- 7.6. Of these, 78% required hospitalization. The most common
reason for hospitalization was acute respiratory tract infection. Thirty-five
percent had health insurance coverage; 54% had sought care more than once at a
different facility. Only 15% of NBIs had a highly complex condition that should
have actually been solved at HG. CONCLUSION: Based on the analysis of NBIs seen
at HG through spontaneous demand for services, a high requirement of
hospitalization for low and medium complexity pathologies was observed.
PMID- 28504492
TI - Salivary and serum cortisol levels in newborn infants.
AB - INTRODUCTION: Given that serum cortisol level interpretation in newborn infants
(NBIs) is hard, the objective of this study was to correlate baseline salivary
and serum cortisol levels and to describe salivary cortisol levels in the first
month of life. POPULATION AND METHODS: Descriptive, prospective, longitudinal,
and correlational study. Term NBIs were selected from the Division of Neonatology
of Hospital Nacional Profesor Alejandro Posadas in 2014. Cortisol was measured in
saliva specimens while cortisol, cortisol-binding globulin, and albumin were
measured in blood specimens. A linear correlation was performed to relate serum
and salivary cortisol levels; Friedman test was conducted to compare cortisol
levels during the first month of life, and the difference was used to analyze the
performance of values equal to or lower than the first quartile. RESULTS: Fifty
five NBIs were studied. Serum cortisol: 7.65 (1.0-18.1 gg/dL); salivary cortisol:
35.88 (5.52-107.64 mmol/L); cortisol-binding globulin: 22.07 (16.5-33.0 gg/mL),
expressed as median and range. The correlation coefficient between serum and
salivary cortisol was 0.54, P = 0.001. Cortisol performance during the first
month of life showed no statistically significant differences, and the difference
between the second and the first specimen of values equal to or lower than the
first quartile increased in 10 out of 12 patients. CONCLUSION: The measurement of
cortisol in saliva reflects serum cortisol levels in normal NBIs. Some patients
had low levels of cortisol at 36 hours of life and showed a trend towards a
spontaneous increase during the first month of life.
PMID- 28504493
TI - Neuropsychological assessment among children and adolescents with phenylketonuria
and hyperphenylalaninemia and its relationship with plasma phenylalanine levels.
AB - Although with early treatment phenylketonuria patients may have average
intelligence levels, it is important to optimize the nutritional management to
maintain adequate phenylalanine levels, so that patients can develop their
intellectal potential free of abnormalities in their daily activities due to
deficits of cognitive executive functions. This study presents a series of 26
patients, diagnosed and treated early, who underwent a psychometric evaluation
together with phenylalanine determinations along their lives, and at the time of
doing the tests. A trend is observed towards a reverse relationship between IQ
and concurrent phenylalanine concentration, phenylalanine median and
phenylalanine/tyrosine ratio. Likewise, a trend towards a negative relationship
is observed between executive functions and concurrent phenylalanine values along
patients' lives.
PMID- 28504494
TI - Staphylococcus aureus nasal carriage and its antibiotic resistance profiles in
children in high altitude areas of Southwestern China.
AB - BACKGROUND/AIM: To describe the epidemiological profile of nasal carriage of
Staphylococcus aureus (S. aureus) strains, its antibiotic resistance and mecA and
Panton Valentine leukocidin (PVL) genes presence, in school children residing in
high altitude areas of Southwestern China. METHODS: The cross sectional study
screened nasal swabs taken from students for S.aureus. PCR was performed to
identify mecA and PVL genes. RESULTS: Of the total 314 children 5.10% (16/314)
was detected S.aureus. The resistance of isolated strains to penicillin,
erythromycin, clindamycin, rifampicin and cefoxitin was 100%, 81.3%, 81.3%, 0.0%,
and 6.3% respectively. No strains demonstrated resistance to vancomycin;
expression of mecA gene was detected in 3 isolates and 10 isolates were PVL
positive. CONCLUSION: S. aureus was detected in 5.10% (16/314) of the study
population; 0.96% (3/314) had methicillin resistant S.aureus (MRSA); expression
of the mecA and PVL genes were detected in 3 and 10 isolates respectively.
PMID- 28504495
TI - Early use of continuous positive airway pressure in the treatment of moderate to
severe acute lower respiratory tract infections among patients younger than 2
years old.
AB - OBJETIVE: To analyze the characteristics of patients younger than 2 years old who
had a moderate to severe acute lower respiratory tract infection and were treated
early with bubble continuous positive airway pressure, and factors associated
with a successful intervention. METHOD: Retrospective and descriptive study.
Children younger than 2 years old admitted to the Pediatric Intermediate Care
Unit of Hospital Provincial Neuquen between June 2009 and December 2010. Bubble
continuous positive airway pressure was used, and the following outcomes were
measured: heart rate, respiratory rate, Tal's score, oxygen saturation, and
fraction of inspired oxygen at 0, 2, 6, 24, and 48 h. RESULTS: One hundred and
twenty patients were included. Their median age was 3 months old. The
intervention was successful in 72% of patients. At 2 h, a 15% reduction in
respiratory rate, and a 2-point decrease in Tal's score were predictors of
success, with an odds ratio of 6.41 (95% confidence interval: 2.68-15.36), and of
9.07 (95% confidence interval: 3.72-22.19), respectively. CONCLUSIONS: A
reduction in respiratory rate, heart rate, and Tal's score at 2 hours of starting
the intervention were predictors of success.
PMID- 28504496
TI - Echinococcosis in children: Experience in a tertiary care hospital outside the
endemic area.
AB - Echinococcosis is a zoonotic disease that is widely spread across Argentina and
worldwide. It is acquired during childhood but it is more common during
adulthood. The pediatric population accounts for 10-20% of all cases. This study
included 47 children diagnosed with echinococcosis over a 20-year period. Their
median age was 8 years old (range: 3-17); most patients had some epidemiological
history, such as having lived or living in an endemic or rural area and/ or
having dogs that are fed with viscera. Findings included 85% of single cysts in
only one parenchyma. Cysts were most commonly located in the liver and lungs.
Medical/surgical treatment was carried out in 45 patients (96%). Subsequent
complications were observed in 13 patients (28%), which were more common in those
with lung cysts. Three patients (6%) relapsed 1-24 months later and required a
new surgery. No patient died as a result of the parasitic disease.
PMID- 28504497
TI - Liver disease and dyslipidemia as a manifestation of lysosomal acid lipase
deficiency (LAL-D). Clinical and diagnostic aspects, and a new treatment. An
update.
AB - Lysosomal acid lipase deficiency (LAL-D) is still a little recognized genetic
disease with significant morbidity and mortality in children and adults. This
document provides guidance on when to suspect LAL-D and how to diagnose it. It is
recommended to add lysosomal acid lipase deficiency to the List of differential
diagnoses of sepsis, oncological diseases, storage diseases, persistent diarrhea,
chronic malnutrition, and hemophagocytic lymphohistiocytosis. It should also be
considered in young patients with dyslipidemia and atherosclerosis as well as
diseases associated with fatty liver and/or hepatomegaly. LAL-D should be
suspected in patients with hepatomegaly, hyperlipidemia and /or elevated
transaminases found during routine checks or testing for other conditions, and in
patients with cryptogenic cirrhosis. At present, there is the option of a
specific enzyme replacement treatment.
PMID- 28504498
TI - [Pediatric case report: Spinal epidural abscess].
AB - Spinal epidural abscess is an uncommon pathology. It has an incidence of one case
per 100 000 individuals. An increase is observed due to the raise of risk factors
such as diabetes mellitus, spinal abnormalities, tattoos, acupuncture, epidural
analgesia, and a greater availability of imaging methods. It is a purulent
collection located between the dura and the medullary canal. The most common
germs are Staphylococcus aureus and Gram-negative bacteria. Without timely
treatment, it evolves to medullary compression and permanent neurological
sequelae. An 11-year-old girl was admitted with fever of 48 hs evolution, left
lower back pain, antalgic gait with lumbar stiffness. Neurological examination
was normal. Blunt blistering lesions were observed on lower limbs. Magnetic
resonance imaging showed an image compatible with spinal epidural abscess. The
evolutionwas favorable. Treatment consisted of surgical drainage and antibiotics
for 6 weeks. From the culture of the material obtained, methidllin-sensitive
Staphylococcus aureus was isolated.
PMID- 28504499
TI - [Transverse vaginal septum diagnosed in sisters. Cases report].
AB - Transverse vaginal septum is a disorder that would arise from a failure in the
fusion and/or channeling of the urogenital sinus and the mullerian ducts with low
frequency but with a significant impact on the health of patients. The treatment
is surgical and it will depend on the location and thickness of the septum.
Sometimes, it described a female sex-limited autosomal recessive transmission but
few cases of family association have been reported. We present the cases of two
sisters who had this rare entity 5 years apart and were diagnosed by the
presentation of an intense hypogastric abdominal pain at the age of 11 and 12
years when they had a Tanner stage III pubertal development and primary
amenorrhea.
PMID- 28504500
TI - Infantile-onset thiamine responsive megaloblastic anemia syndrome with SLC19A2
mutation: a case report.
AB - BACKGROUND: Thiamine-responsive megaloblastic anemia syndrome (TRMA), also known
as Rogers syndrome, is characterized by megaloblastic anemia, sensorineural
hearing loss, and diabetes mellitus. Disturbances of the thiamine transport into
the cells results from homozygous or compound heterozygous mutations in the
SLC19A2 gene. CASE PRESENTATION: We report a girl which presented with
sensorineural deafness treated with a hearing prosthesis, insulin requiring
diabetes, macrocytic anemia, treated with thiamine (100 mg/day). Hemoglobin level
improved to 12.1 g/dl after dose of thiamine therapy increased up to 200 mg/day.
CONCLUSION: Patients with TRMA must be evaluated for megaloblastic anemia,
sensorineural hearing loss, and diabetes mellitus. They must be followed for
response of hematologic and diabetic after thiamine therapy. It should be kept in
mind that dose of thiamine therapy may be increased according to the clinical
response. Genetic counseling should be given.
PMID- 28504501
TI - [Bowel obstruction by hamartomatous polyp in a pediatric patient with tuberous
sclerosis].
AB - Tuberous sclerosis is an autosomal dominant disorder with a wide clinical
spectrum of disease. It is characterized by development of benign tumors in
multiple organs due to a disturbance in cellular growth and differentiation. It
usually affects skin, brain, heart and kidney. Gastrointestinal involvement is
rare and mainly restricted to adults and sigmoid colon and rectum. In children
there are only two cases; our patient would be the third. We present a patient
with tuberous sclerosis who began at the first month of life with repeated
intestinal subocclusion. The videocolonoscopy showed a mass protruding into the
lumen of the ascending colon. Right hemicolectomy was performed. The
anatomopathological report corresponded to a hamartomatous polyp. The clinical
and nutritional evolution in the postoperative period was very favorable.
Although uncommon, the hamartomatous polyp should be considered in the
differential diagnosis of intestinal occlusion in pediatrics.
PMID- 28504502
TI - [Transient congenital hypothyroidism due to biallelic defects of DUOX2 gene. Two
clinical cases].
AB - Congenital hypothyroidism affects 1:2000-3000 newborns detected by neonatal
screening programs. Dual oxidases, DUOX1 and 2, generate hydrogen peroxide needed
for the thyroid hormone synthesis. Hipotiroidismo congenito transitorio por
defectos bialelicos del gen DUOX2. Dos casos clinicos Transient congenital
hypothyroidism due to biallelic defects of DUOX2 gene. Two clinical cases
Mutations in the DUOX2 gene have been described in transient and permanent
congenital hypothyroidism. Two brothers with congenital hypothyroidism detected
by neonatal screening with eutopic gland and elevated thyroglobulin are
described. They were treated with levothyroxine until it could be suspended in
both during childhood, assuming the picture as transient. Organification disorder
was confirmed. Both patients were compounds heterozygous for a mutation in exon 9
of the paternal allele (c.1057_1058delTT, p.F353PfsX36 or p.F353fsX388) and in
exon 11 of the maternal allele (c.1271T > G, p.Y425X) of DUOX2 gene. Our finding
confirms that the magnitude of the defect of DUOX2 is not related to the number
of inactivated alleles, suggesting compensatory mechanisms in the peroxide
supply.
PMID- 28504503
TI - [Cervicofacial actinomycosis as differential diagnosis of cavum carcinoma: case
report].
AB - Paediatric actinomycosis is an infrequent infectious disease caused by
Actinomyces spp. Cervicofacial infections are usually related to disruption in
oral mucosal membranes. We discuss the case of a 15-year-old girl who refers an 8
month history of odynophagia and changes in her tone of voice after getting a
tongue piercing. She received multiple antibiotic treatments with slight
improvement. Nasopharyngeal carcinoma was diagnosed by endoscopic biopsy. The
patient was referred to our Hospital for treatment but, when the biopsy was
analyzed again, oncological pathology was excluded and oropharyngeal
actinomycosis was diagnosed. She received a total of 6 months of antibiotic
treatment with favorable evolution. While oral piercings have not been yet
described as a risk factor for oropharyngeal actinomycosis, the mucosal
disruption could favor the onset of this disease.
PMID- 28504504
TI - [Cornelia de Lange Syndrome and multiple hormonal deficiency, an unusual
association. Clinical case].
AB - Cornelia de Lange syndrome is a genetic disease characterized by distinctive
facial features, failure to thrive, microcephaly and several malformations
associated. Its main endocrinological features are anomalies of the genitalia. We
present a 13-year-old boy, who suffered from complicated aspiration pneumonia and
showed Cornelia de Lange syndrome phenotype, with global developmental delay,
suction-swallowing abnormalities, short stature and abnormal genitalia
associated. His bone age was delayed, so he underwent full endocrinological
panel. Central hypothyroidism, growth hormone deficiency and low luteinizing
hormone-follicle-stimulating hormone levels were observed and multiple pituitary
hormone deficiencies diagnosis was made. Basal cortisol, adrenocorticotropic
hormone and prolactin levels were normal. He received thyroid hormonal
substitution. Multiple pituitary hormone deficiencies are an unusual feature of
De Lange syndrome. We suggest evaluating all different endocrine axes in these
patients.
PMID- 28504505
TI - Retinovascular findings in newborns with critical congenital heart disease: A
case series.
AB - Critical congenital heart disease (CCHD) may cause changes in retinal
vasculature. However, there is lack of data in this issue in newborns. We
evaluated retinovascular changes in a series of 43 newborn with CCHD. They were
divided into 2 groups according to the type of CCHD; group 1 (n= 18): left
obstructive CCHD and group 2 (n= 25): right obstructive CCHD. Retinovascular
pathologies were detected in 21 patients (48.8%); it was more frequent in group 1
(p= 0.04). The most common pathology was retinal vascular tortuosity in 6
patients (33.3%) of group 1, and 4 (16.0%) in group 2. None of 21 patients with
retinovascular changes required any therapy at follow-up. In multivariate
analysis, only having a left obstructive CCHD was associated with the development
of any retinovascular pathology (P= 0.03, OR: 2.8, CI95%: 1.1-7.4).
Retinovascular changes are frequent in newborn patients with CCHD.
PMID- 28504506
TI - [A very rare cause of peripheral precocious puberty in a girl: ovarian sex cord
tumor with annular tubules].
AB - Sex cord tumor with annular tubules is an extremely uncommon gonadal stromal
neoplasm. It represents 0.05-0.6% of all ovarian tumors, according to series. An
unusual case is presented in a 6-year-old girl, detected as a result of an
isosexual peripheral precocious puberty. The highlight of this case is that no
mass attached to the ovary was found, but only a gonadal asymmetry without
radiological signs of malignancy. After confirming the presence of tumoral cells
by intraoperative biopsy, unilateral salpingo-oophorectomy with ipsilateral para
aortic and pelvic lymphadenectomy was performed. Afterwards, the evolution of the
patient was favorable.
PMID- 28504507
TI - [Mosaic trisomy 18. Series of cases].
AB - Trisomy 18 syndrome (T18) is a clinical and genetic disorder, which has a full
extra chromosome 18 in each cell, variant that is called free trisomy. In
addition, it can occur in partial and mosaic form. It is characterized by
intrauterine growth restriction, psychomotor and mental retardation,
characteristic craniofacial findings, congenital heart disease, hypoplastic
pelvis, clenched hand and rocker-bottom foot, among others. The mosaic T18 occurs
when cells with T18 and normal cell lines exist in the same individual and
correspond to 5% of cases. Trisomia 18 en mosaico. Serie de casos Mosaic trisomy
18. Series of cases The phenotypic findings are highly variable and no
correlation was evident between the percentage of trisomic cells and the findings
found. The aim of this report is to present a series of five cases of mosaic T18
with emphasis on clinical aspects in order to guide an interdisciplinary adequate
medical care and provide timely genetic counseling.
PMID- 28504508
TI - [Mistakes in drug prescription during simulated pediatric resuscitations and
other urgency procedures].
AB - INTRODUCTION: The probability of making mistakes in the prescription of medicines
is high in pediatrics, and substantially increases in emergency situations.
MATERIAL AND METHODS: This prospective observational study analyzed the
prescriptions issued by physicians during 23 cardiopulmonary resuscitation
pediatric emergency training sessions. RESULTS: During 94 simulated cases, 96
physicians participated. Forty-four prescriptions on paper were analyzed (48%)
including 120 doses. Twelve medication errors were found (10%, CI 95%: 5.517.2).
Stress was identified as the primary cause of prescription mistakes. CONCLUSIONS:
Drug prescription mistakes frequently occurred during pediatric emergency
simulations.
PMID- 28504509
TI - [Recommendation for therapeutic hypothermia in newborns with hypoxic-ischemic
encephalopathy.
PMID- 28504510
TI - [Guide for monitoring children's development in pediatric practice].
AB - The pediatrician is the best-informed professional to whom many families look to
be the expert, not only on childhood illnesses but also on development. Early
identification, diagnosis and monitoring of these patients are a real challenge
for physicians who serve children. This guide provides recommendations for
development monitoring, evaluation, diagnosis and follow up of patients with
developmental delays and disabilities.
PMID- 28504511
TI - [Intrauterine growth restriction: endocrinological perspective. Update of the
2007 version (Arch Argent Pediatr 2007;105(1):71-73)].
AB - Most children born with low weight or intrauterine growth restriction develop
catch-up growth that allows them to reach a final height according to their
genetic target height. However, in about 15% of children this growth is
insufficient. In both, children who have adequate compensatory growth and
therefore normal height and children who remain low in childhood, it is necessary
to take into account that if puberty starts early, the final height could be
compromised. Timely and appropriate intervention could improve it. Control of
body weight is also important, as an excessive gain in childhood is associated
with metabolic complications in adolescence and adult life.
PMID- 28504512
TI - Fully Printable Organic and Perovskite Solar Cells with Transfer-Printed Flexible
Electrodes.
AB - The perovskite solar cells (PSCs) and organic solar cells (OSCs) with high
performance were fabricated with transfer-printed top metal electrodes. We have
demonstrated that PSCs and OSCs with the top Au electrodes fabricated by using
the transfer printing method have comparable or better performance than the
devices with the top Au electrodes fabricated by using the conventional thermal
evaporation method. The highest PCE of the PSCs and OSCs with the top electrodes
fabricated using the transfer printing method achieved 13.72% and 2.35%,
respectively. It has been investigated that fewer defects between the organic
thin films and Au electrodes exist by using the transfer printing method which
improved the device stability. After storing the PSCs and OSCs with the transfer
printed electrodes in a nitrogen environment for 97 and 103 days without
encapsulation, the PSCs and OSCs still retained 71% and 91% of their original
PCEs, respectively.
PMID- 28504513
TI - Photomanipulated Architecture and Patterning of Azopolymer Array.
AB - Here reported is the approach to prepare the tunable 3D architecture and
patterning through photoinduced orientation of azopolymer. The hemispherical
PAzoMA array can be transformed into spindlelike, flat ellipsoidlike, thick
spindlelike, near-hexagon, near-quadrangle, and near-rhombus arrays while being
exposed to linearly polarized light (LPL). The size and alignment of the arrays
can be precisely controlled by manipulating the irradiation time. Furthermore,
complex 3D architectures of the PAzoMA array are readily fabricated through
secondary irradiation along different direction. This technique is promising for
functionalized surfaces and photonic devices.
PMID- 28504514
TI - Why Life Cycle Assessment Does Not Work for Synthetic Biology.
PMID- 28504515
TI - The Catalytically Lignan-Activation-Based Approach for the Synthesis of (epi)
Podophyllotoxin Derivatives.
AB - Under the effect of a catalytic amount of Au(I) complex, 4-O-(2
cyclopropylethynyl)benzoyl-(epi)-podophyllotoxins, easily prepared via
dehydrative condensation between (epi)-podophyllotoxin and ortho
cyclopropylethynylbenzoic acid, could efficiently couple with a variety of
nucleophiles including alcohol, phenol, aniline, and carbon nucleophiles, all to
provide (epi)-podophyllotoxin derivatives. Thus, the first catalytic and lignan
activation-based approach for (epi)-podophyllotoxin derivatization was
established. Based on the new methodology, as well as the judicious choice of N3,
AZMB, and Cbz protecting groups, an efficient approach forward was set. NK-611,
an antitumoral agent at a phase II clinical trial was established, featuring an
in situ anomerization of the hemiacetal OHs in the critical condensation step.
Commencing from easily available starting material, the target molecule was
obtained using the longest linear sequence of six steps and a 38% overall yield.
PMID- 28504516
TI - Self-Associated Polyamide Alloys with Tailored Polymorphism Transition and
Lamellar Thickening for Advanced Mechanical Application.
AB - Long chain polyamides with various number of methylene units in recurring amide
groups, PA1012 and PA612, were blended to combine their unique advantages. The
Brill transition and accompanied lamellar thickening were investigated by in situ
wide angle X-ray scattering (WAXS) and small angle X-ray scattering. From WAXS
patterns, the transformation from the alpha- to gamma-crystalline phase, known as
"Brill transition", can be independently observed in the constituent phases of
the long chain polyamide alloys (LCPAs) during heating. A constant Tb (ca., 100
degrees C) irrespective of the blend composition and proportional variations of
the phase content was obtained. Additionally, with elevated temperature, a
gradual increase in both the crystalline layer (Lc) and amorphous layer (La) was
detected in constituent polyamides. The compositional independence of the Brill
transition in LCPAs and similar lamellar thickening originate from the complete
immiscibility of both polyamides, which share stronger intramolecular rather than
intermolecular hydrogen-bonding interaction and hence exhibit self-association.
Contributed by the gamma phase, with less extended structure and increased
lamellar thickness with compact stacking, LCPAs with controlled strength and
flexible features can be achieved, which can be utilized in advanced mechanical
applications, particularly for hoses of automobiles. The unusually linear
compositional dependence of mechanical parameters makes it possible to tailor the
polymorphic and tensile properties.
PMID- 28504517
TI - Near-Infrared Fluorescent Turn-on Probe with a Remarkable Large Stokes Shift for
Imaging Selenocysteine in Living Cells and Animals.
AB - Selenocysteine (Sec) is the 21st naturally occurring amino acid and has emerged
as an important sensing target in recent years. However, fluorescent detection of
Sec in living systems is challenging. To date, very few fluorescent Sec probes
have been reported and most of them respond fluorescence to Sec in the visible
region. In this paper, a very promising near-infrared fluorescent probe for Sec
was developed. This probe works in aqueous solution over a wide pH range under
mild conditions and can be used for rapid, highly selective and sensitive
detection of Sec with significant near-infrared fluorescent turn-on signal
changes. In addition, it features a remarkable large Stokes shift (192 nm) and a
low detection limit (60 nM) for Sec with a wide linear range (0-70 MUM).
Moreover, this probe can be conveniently used to detect Sec in serum samples,
living cells, and animals, indicating it holds great promise for biological
applications.
PMID- 28504518
TI - A Breakthrough Efficiency of 19.9% Obtained in Inverted Perovskite Solar Cells by
Using an Efficient Trap State Passivator Cu(thiourea)I.
AB - It is extremely significant to study the trap state passivation and minimize the
trap states of perovskite to achieve high-performance perovskite solar cells
(PSCs). Here, we have first revealed and demonstrated that a novel p-type
conductor Cu(thiourea)I [Cu(Tu)I] incorporated in perovskite layer can
effectively passivate the trap states of perovskite via interacting with the
under-coordinated metal cations and halide anions at the perovskite crystal
surface. The trap state energy level of perovskite can be shallowed from 0.35
0.45 eV to 0.25-0.35 eV. In addition, the incorporated Cu(Tu)I can participate in
constructing the p-i bulk heterojunctions with perovskite, leading to an increase
of the depletion width from 126 to 265 nm, which is advantageous for accelerating
hole transport and reducing charge carrier recombination. For these two
synergistic effects, Cu(Tu)I can play a much better role than that of the
traditional p-type conductor CuI, probably due to its identical valence band
maximum with that of perovskite, which enables to not only lower the trap state
energy level to a greater extent but also eliminate the potential wells for holes
at the p-i heterojunctions. After optimization, a breakthrough efficiency of
19.9% has been obtained in the inverted PSCs with Cu(Tu)I as the trap state
passivator of perovskite.
PMID- 28504519
TI - Longitudinal associations between adult children's relations with parents and
intimate partners.
AB - Drawing on 5 waves of multiple-informant data gathered from focal participants
and their parents and intimate partners (n = 360 families) who completed annual
surveys in the German Family Panel (pairfam) study, the present investigation
examined bidirectional associations between the development of adults'
conflictual and intimate interactions with their parents and intimate partners.
Autoregressive cross-lagged latent change score modeling results revealed a
robust pattern of coordinated development between parent-adult child and couple
conflictual and intimate interactions: increases in conflict and intimacy in one
relationship were contemporaneously intertwined with changes in the other
relationship. Additionally, prior couple intimacy and conflict predicted future
parent-adult child relations in 7 out of 14 cross-lagged pathways examined, but
parent-adult child conflict and intimacy was only associated with future couple
interactions in 1 pathway. These associations were not moderated by the gender of
parents or the adult child or whether the adult child was a young adult or
nearing midlife. Frequency of contact between parents and the adult child
moderated some associations. Adults simultaneously juggle ties with parents and
intimate partners, and this study provides strong evidence supporting the
coordinated development of conflictual and intimate patterns of interaction in
each relationship. (PsycINFO Database Record
PMID- 28504520
TI - Prayer and forgiveness: Beyond relationship quality and extension to marriage.
AB - The majority of the world population profess religious/spiritual beliefs and
prayer is a form of spiritual activity common across numerous religious/spiritual
belief systems. Three studies therefore examined the role of prayer in romantic
relationships. Study 1 (n = 91) showed that prayer for a dating partner predicted
lower aggressive tendencies and greater forgiveness of partner transgressions,
independently of relationship closeness. Study 2 (n = 89 married couples) is
among the first to examine the prayer-forgiveness association using dyadic data.
Controlling for relationship satisfaction in the actor-partner interdependence
model, prayer for the spouse predicted own forgiveness but not partner's reports
of their own forgiveness. To obviate the problem of obtaining all the data from
the same reporter, Study 3 (n = 91 married couples) used partner reports of the
spouse's forgiveness in an actor-partner interdependence model analysis.
Controlling for religiosity, the results showed that prayer for the partner
predicted partner reports of the prayer's forgiveness. The implications of these
results are then discussed. (PsycINFO Database Record
PMID- 28504522
TI - The construct-behavior gap in behavioral decision research: A challenge beyond
replicability.
AB - Behavioral decision research compares theoretical constructs like preferences to
behavior such as observed choices. Three fairly common links from constructs to
behavior are (1) to tally, across participants and decision problems, the number
of choices consistent with one predicted pattern of pairwise preferences; (2) to
compare what most people choose in each decision problem against a predicted
preference pattern; or (3) to enumerate the decision problems in which two
experimental conditions generate a 1-sided significant difference in choice
frequency 'consistent' with the theory. Although simple, these theoretical links
are heuristics. They are subject to well-known reasoning fallacies, most notably
the fallacy of sweeping generalization and the fallacy of composition. No amount
of replication can alleviate these fallacies. On the contrary, reiterating
logically inconsistent theoretical reasoning over and again across studies
obfuscates science. As a case in point, we consider pairwise choices among simple
lotteries and the hypotheses of overweighting or underweighting of small
probabilities, as well as the description-experience gap. We discuss ways to
avoid reasoning fallacies in bridging the conceptual gap between hypothetical
constructs, such as, for example, "overweighting" to observable pairwise choice
data. Although replication is invaluable, successful replication of hard-to
interpret results is not. Behavioral decision research stands to gain much
theoretical and empirical clarity by spelling out precise and formally explicit
theories of how hypothetical constructs translate into observable behavior.
(PsycINFO Database Record
PMID- 28504521
TI - Family dinner frequency interacts with dinnertime context in associations with
child and parent BMI outcomes.
AB - For youth and parents, frequent family meals have been consistently associated
with positive dietary outcomes but less consistently associated with lower body
mass index (BMI). Researchers have speculated dinnertime context (dinnertime
routines, parent dinnertime media use) may interact with family meal frequency to
impact associations with BMI. The present study evaluates the associations and
interactions between dinnertime context measures and family dinner frequency with
parent and child BMI. This cross-sectional study uses baseline data from the
Healthy Home Offerings via the Mealtime Environment (HOME) Plus randomized
control trial that aimed to prevent childhood obesity. Participants (160 parent
child dyads) completed psychosocial surveys and were measured for height and
weight. General linear models tested associations and interactions between
dinnertime context measures and family dinner frequency with parent and child
BMI, adjusted for race and economic assistance. Lower parent dinnertime media use
and higher dinnertime routines were significantly associated with lower child BMI
z scores but not parent BMI scores. Interaction-moderation findings suggest
higher family dinner frequency amplifies the healthful impact of the dinnertime
context on child BMI z scores. Additionally, findings emphasize that promoting
frequent family meals along with consistent routines and reduction in parent
dinnertime media use may be important for the prevention of childhood obesity.
(PsycINFO Database Record
PMID- 28504524
TI - Healthy aging is associated with decreased risk-taking in motor decision-making.
AB - Healthy aging is associated with changes in both cognitive abilities, including
decision-making, and motor control. Previous research has shown that young
healthy observers are close to optimal when they perform a motor equivalent of
economic decision-making tasks that are known to produce suboptimal decision
patterns. We tested both younger (age 20-29) and older (age 60-79) adults in such
a task, which involved rapid manual aiming and monetary rewards and punishments
contingent on hitting different areas on a touch screen. Older adults were as
close to optimal as younger adults at the task, but differed from the younger
adults in their strategy. Older adults appeared to be relatively less risk
seeking, as evidenced by the fact that they adjusted their aiming strategy to a
larger extent to avoid the penalty area. A model-based interpretation of the
results suggested that the change in aiming strategy between younger and older
adults was mainly driven by the fact that the first weighted monetary gains more
than losses, rather than by a mis-estimation of one's motor variability. The
results parallel the general finding that older adults tend to be less risk
seeking than younger adults in economic decision-making and complement the
observation that children are even more risk-seeking than younger adults in a
similar motor decision-making paradigm. (PsycINFO Database Record
PMID- 28504523
TI - Decomposition of a sensory prediction error signal for visuomotor adaptation.
AB - To accomplish effective motor control, the brain contains an internal forward
model that predicts the expected sensory consequence of a motor command. When
this prediction is inaccurate, a sensory prediction error is produced which
adapts the forward model to make more accurate predictions of future movements.
Other types of errors, such as task performance errors or reward, play less of a
role in adapting a forward model. This raises the following question: What unique
information is conveyed by the sensory prediction error that results in forward
model adaptation? sensory prediction errors typically contain both the magnitude
and direction of the error, but it is unclear if both components are necessary
for adaptation or a single component is sufficient. In this article, we address
this by having participants learn to counter a visuomotor rotation, which induces
an angular mismatch between movements of the hand and visual feedback. We
manipulated the information content of the visual feedback, in the form of a
line, which accurately represented only the magnitude (distance), direction, or
both magnitude and direction, of the virtual cursor relative to the target. We
demonstrate that sensorimotor adaptation does not occur, or is minimal, when
feedback is limited to information about the magnitude of an error. In contrast,
sensorimotor adaptation is present when feedback is limited only to the direction
of an error or when it contains combined direction and magnitude information.
This result stands in contrast to current computational models of cerebellar
based sensorimotor adaptation that use error magnitude to drive adaptation.
(PsycINFO Database Record
PMID- 28504525
TI - Introspection of subjective feelings is sensitive and specific.
AB - Conversely to behaviorist ideas, recent studies suggest that introspection can be
accurate and reliable. However, an unresolved question is whether people are able
to report specific aspects of their phenomenal experience, or whether they report
more general nonspecific experiences. To address this question, we investigated
the sensitivity and validity of our introspection for different types of
conflict. Taking advantage of the congruency sequence effect, we dissociated
response conflict while keeping visual conflict unchanged in a Stroop and in a
priming task. Participants were subsequently asked to report on either their
experience of urge to err or on their feeling of visual conflict. Depending on
the focus of the introspection, subjective reports specifically followed either
the response conflict or the visual conflict. These results demonstrate that our
introspective reports can be sensitive and that we are able to dissociate
specific aspects of our phenomenal experiences in a valid manner. (PsycINFO
Database Record
PMID- 28504526
TI - Endogenous formation of preferences: Choices systematically change willingness-to
pay for goods.
AB - Standard decision theory assumes that choices result from stable preferences.
This position has been challenged by claims that the act of choosing between
goods may alter preferences. To test this claim, we investigated in three
experiments whether choices between equally valued snack food items can
systematically shape preferences. We directly assessed changes in participants'
willingness-to-pay for these items, some of which could be bought at an auction
after the experiment, while others could not. We found that chosen items were
valued higher, and nonchosen items were valued lower; yet this postdecisional
refinement of preferences was only observed for choices and valuations that were
relevant, that is, incentive-compatible for items that were available for
consumption. Supplementary analyses revealed that incentive-incompatible
elicitations of preferences were unreliable and may have masked potential effects
of choices on preferences. In conclusion, we propose that preferences can change
endogenously, that is, in the absence of external feedback or information, but
rather as a function of previous relevant choices. (PsycINFO Database Record
PMID- 28504527
TI - The testing effect under divided attention.
AB - Memory retrieval often enhances later memory compared with restudying (i.e., the
testing effect), indicating that retrieval does not simply reveal but also
modifies memory representations. Dividing attention (DA) during encoding greatly
disrupts later memory performance while DA during retrieval typically has modest
effects-but what of the memory-modifying effects of retrieval? If these effects
are similar to study-based encoding, they should be greatly disrupted by DA, a
possibility consistent with elaborative and effortful accounts of the testing
effect. Alternatively, the mnemonic consequences of retrieval may be largely
resilient to distraction, like retrieval itself. In 3 experiments, participants
studied word pairs (Phase 1) then engaged in restudy of some pairs and retrieval
of others (Phase 2), followed by a final cued-recall test (Phase 3). Phase 2
restudy and retrieval occurred under full attention (FA) or DA. The experiments
were designed to induce either material-specific (Experiments 1 and 2) or
material-general (Experiment 3) interference, as well as to produce comparable
secondary task performance between the restudy and retrieval groups (Experiments
2 and 3). Consistent with prior research, retrieval improved final recall (i.e.,
the testing effect) whereas DA disrupted final recall. Critically, the 2 factors
interacted such that the negative effect of DA on final recall was substantial in
the restudy condition but quite modest in the retrieval condition-resulting in a
larger testing effect in the DA than FA condition. The encoding effects of
retrieval seem resilient to distraction which has implications for theories of
the testing effect. (PsycINFO Database Record
PMID- 28504528
TI - The importance of arousal for variation in working memory capacity and attention
control: A latent variable pupillometry study.
AB - A great deal of prior research has examined the relation between working memory
capacity (WMC) and attention control. The current study explored the role of
arousal in individual differences in WMC and attention control. Participants
performed multiple WMC and attention control tasks. During the attention control
tasks participants were periodically probed regarding their current attentional
state and both baseline and task-evoked pupillary responses were recorded as
indicators of tonic arousal and phasic arousal because of attentional effort,
respectively. Latent variable analyses demonstrated that variability in both
baseline pupil diameter and task-evoked responses was related to WMC, attention
control, and off-task thinking. Furthermore, structural equation models suggested
that variability in both baseline pupil diameter and task-evoked pupillary
responses predicted off-task thinking, which in turn predicted variation in WMC
and attention control. These results provide important evidence linking moment-to
moment fluctuations in arousal to individual differences in WMC and attention
control. (PsycINFO Database Record
PMID- 28504529
TI - The cause of category-based distortions in spatial memory: A distribution
analysis.
AB - Recall of remembered locations reliably reflects a compromise between a target's
true position and its region's prototypical position. The effect is quite robust,
and a standard interpretation for these data is that the metric and categorical
codings blend in a Bayesian combinatory fashion. However, there has been no
direct experimental evidence that the 2 codings are actually combined. That is,
at least 2 mechanisms can produce biased mean responses: (a) people may in fact
take a weighted average of the metric and categorical representations, but (b)
these 2 codings may instead compete for response, each winning with a certain
probability. The present work investigated these 2 hypotheses for the cause of
category-based distortions using a new distribution analysis. Participants viewed
a target within a blank circle and reproduced its location after a short delay.
The error data for individual participants were fit with a kernel curve, which
provides a distribution without the assumption of normality. Almost all
individual distributions displayed a clear biased main peak, indicating a
weighted average between the representations, not an alteration between the 2
representations. (PsycINFO Database Record
PMID- 28504530
TI - Framing affects scale usage for judgments of learning, not confidence in memory.
AB - Framing metacognitive judgments of learning (JOLs) in terms of the likelihood of
forgetting rather than remembering consistently yields a counterintuitive
outcome: The mean of participants' forget-framed JOLs is often higher (after
reverse-scoring) than the mean of their remember-framed JOLs, suggesting greater
confidence in memory. In the present experiments, we tested 2 competing
explanations for this pattern of results. The optimistic-anchoring hypothesis
suggests that forget-framed JOLs are associated with greater optimism about
memory than are remember-framed JOLs, which leads to their greater magnitude. The
differential-scaling hypothesis suggests that forget-framed JOLs and remember
framed JOLs will often be distributed differently across the JOL scale, resulting
in means that also often differ. Participants in 3 experiments studied simple
memory materials and made JOLs predicting their memory performance for those
items. They made their JOLs in terms of either the likelihood of remembering or
forgetting. In contrast to the optimistic-anchoring hypothesis, the mean of
participants' forget-framed JOLs was unaffected by information concerning the
supposed difficulty of the task (Experiment 1), was lower than for remember
framed JOLs in a task selected to evoke high JOLs (Experiment 2), and
demonstrated equivalent confidence in memory when participants were restricted to
a yes-no binary response (Experiment 3). In support of the differential-scaling
hypothesis, participants' forget-framed JOLs were consistently symmetrically
distributed across the JOL scale, resulting in a mean at the center of the
judgment scale that was often higher than that for remember-framed JOLs. Framing
therefore affects how participants scale their JOLs, not their confidence in
their memory. (PsycINFO Database Record
PMID- 28504531
TI - The role of familiarity in correcting inaccurate information.
AB - People frequently continue to use inaccurate information in their reasoning even
after a credible retraction has been presented. This phenomenon is often referred
to as the continued influence effect of misinformation. The repetition of the
original misconception within a retraction could contribute to this phenomenon,
as it could inadvertently make the "myth" more familiar-and familiar information
is more likely to be accepted as true. From a dual-process perspective,
familiarity-based acceptance of myths is most likely to occur in the absence of
strategic memory processes. Thus, we examined factors known to affect whether
strategic memory processes can be utilized: age, detail, and time. Participants
rated their belief in various statements of unclear veracity, and facts were
subsequently affirmed and myths were retracted. Participants then rerated their
belief either immediately or after a delay. We compared groups of young and older
participants, and we manipulated the amount of detail presented in the
affirmative or corrective explanations, as well as the retention interval between
encoding and a retrieval attempt. We found that (a) older adults over the age of
65 were worse at sustaining their postcorrection belief that myths were
inaccurate, (b) a greater level of explanatory detail promoted more sustained
belief change, and (c) fact affirmations promoted more sustained belief change in
comparison with myth retractions over the course of 1 week (but not over 3
weeks), This supports the notion that familiarity is indeed a driver of continued
influence effects. (PsycINFO Database Record
PMID- 28504532
TI - Orthography affects second language speech: Double letters and geminate
production in English.
AB - Second languages (L2s) are often learned through spoken and written input, and L2
orthographic forms (spellings) can lead to non-native-like pronunciation. The
present study investigated whether orthography can lead experienced learners of
EnglishL2 to make a phonological contrast in their speech production that does
not exist in English. Double consonants represent geminate (long) consonants in
Italian but not in English. In Experiment 1, native English speakers and
EnglishL2 speakers (Italians) were asked to read aloud English words spelled with
a single or double target consonant letter, and consonant duration was compared.
The EnglishL2 speakers produced the same consonant as shorter when it was spelled
with a single letter, and longer when spelled with a double letter. Spelling did
not affect consonant duration in native English speakers. In Experiment 2,
effects of orthographic input were investigated by comparing 2 groups of
EnglishL2 speakers (Italians) performing a delayed word repetition task with or
without orthographic input; the same orthographic effects were found in both
groups. These results provide arguably the first evidence that L2 orthographic
forms can lead experienced L2 speakers to make a contrast in their L2 production
that does not exist in the language. The effect arises because L2 speakers are
affected by the interaction between the L2 orthographic form (number of letters),
and their native orthography-phonology mappings, whereby double consonant letters
represent geminate consonants. These results have important implications for
future studies investigating the effects of orthography on native phonology and
for L2 phonological development models. (PsycINFO Database Record
PMID- 28504533
TI - Cue integration in spatial search for jointly learned landmarks but not for
separately learned landmarks.
AB - The authors investigated how humans use multiple landmarks to locate a goal.
Participants searched for a hidden goal location along a line between 2 distinct
landmarks on a computer screen. On baseline trials, the location of the landmarks
and goal varied, but the distance between each of the landmarks and the goal was
held constant, with 1 landmark always closer to the goal. In Experiment 1, some
baseline trials provided both landmarks, and some provided only 1 landmark. On
probe trials, both landmarks were shifted apart relative to the previously
learned goal location. Participants searched between the locations specified by
the 2 landmarks and their search locations were shifted more toward the nearer
landmark, suggesting a weighted integration of the conflicting landmarks.
Moreover, the observed variance in search responses when both cues were presented
in their normal locations was reduced compared to the variance on tests with
single landmarks. However, the variance reduction and the weightings of the
landmarks did not always show Bayesian optimality. In Experiment 2, some
participants were trained only with each of the single landmarks. On subsequent
tests with the 2 cues in conflict, searching did not shift toward the nearer
landmark and the variance of search responses of these single-cue trained
participants was larger than their variance on single-landmark tests, and even
larger than the variance predicted by using the 2 landmarks alternatively on
different trials. Taken together, these results indicate that cue combination
occurs only when the landmarks are presented together during the initial learning
experience. (PsycINFO Database Record
PMID- 28504534
TI - Food for happy thought: Glucose protects age-related positivity effects under
cognitive load.
AB - Older adults show a preference for positive information, which disappears under
high task demands. We examined whether glucose can help older adults preserve
their positivity effect (PE) under high cognitive load. One hundred twenty-two
adults (40 young and 42 older in Experiment 1; 40 older in Experiment 2) consumed
a glucose (25 g) or a taste-matched placebo drink and completed an immediate
recall task of emotional word-lists presented under high- and low-load
conditions. Older adults showed PEs for low-load lists. Whereas PEs disappeared
for older-placebo participants for high-load lists, older-glucose participants
retained their positive preference. Providing the brain with extra energy
resources can help older adults achieve PEs even under demanding conditions.
(PsycINFO Database Record
PMID- 28504535
TI - Route repetition and route reversal: Effects of age and encoding method.
AB - Previous research indicates age-related impairments in learning routes from a
start location to a target destination. There is less research on age effects on
the ability to reverse a learned path. The method used to learn routes may also
influence performance. This study examined how encoding methods influence the
ability of younger and older adults to recreate a route in a virtual reality
environment in forward and reverse directions. Younger (n = 50) and older (n =
50) adults learned a route either by self-navigation through the virtual
environment or through studying a map. At test, participants recreated the route
in the forward and reverse directions. Older adults in the map study condition
had greater difficulty learning the route in the forward direction compared to
younger adults. Older adults who learned the route by self-navigation were less
accurate in traversing the route in the reverse compared to forward direction
after a delay. In contrast, for older adults who learned via map study there were
no significant differences between forward and reverse directions. Results
suggest that older adults may not as readily develop and retain a sufficiently
flexible representation of the environment during self-navigation to support
accurate route reversal. Thus, initially learning a route from a map may be more
difficult for older adults, but may ultimately be beneficial in terms of better
supporting the ability to return to a start location. (PsycINFO Database Record
PMID- 28504536
TI - A signal-detection analysis of eyewitness identification across the adult
lifespan.
AB - Middle-aged and older adults are frequently victims and witnesses of crime, but
knowledge of how identification performance changes over the adult life span is
sparse. The authors asked young (18-30 years), middle-aged (31-59 years), and
older (60-95 years) adults (N = 2,670) to watch a video of a mock crime and to
attempt to identify the culprit from a fair lineup (in which all of the lineup
members matched the appearance of the suspect) or an unfair lineup (in which the
suspect stood out). They also asked subjects to provide confidence ratings for
their identification decisions. To examine identification performance, the
authors used a standard response-type analysis, receiver operating characteristic
analysis, and signal-detection process modeling. The results revealed that, in
fair lineups, aging was associated with a genuine decline in recognition ability
discriminability-and not an increased willingness to choose. Perhaps most
strikingly, middle-aged and older adults were generally effective at regulating
their confidence judgments to reflect the likely accuracy of their suspect
identification decisions. Model-fitting confirmed that the older adults spread
their decision criteria such that identifications made with high confidence were
likely to be highly accurate, despite the substantial decline in discriminability
with age. In unfair lineups, ability to discriminate between innocent and guilty
suspects was poor in all age groups. The research enhances theoretical
understanding of the ways in which identification behavior changes with age, and
has important practical implications for how legal decision-makers should
interpret identifications made by middle-aged and older eyewitnesses. (PsycINFO
Database Record
PMID- 28504537
TI - A tale of two measures: Concordance between the ARSMA-II and the BIQ
acculturation scales among Latino immigrant families.
AB - Acculturation refers to the extent to which an individual immigrant (or immigrant
group) acquires the customs and characteristics of a new receiving society and/or
retains the customs and characteristics of the person's or group's cultural
heritage. Different acculturation measures are often assumed to be
interchangeable, although this assumption is rarely tested empirically. The
purpose of the present study was to examine the overlap between 2 commonly used
measures of acculturation among individuals of Latino/Hispanic ancestry in the
United States, the Acculturation Rating Scale for Mexican Americans II (ARSMA-II)
and the Bicultural Involvement Questionnaire-Short Version (BIQ-S). Specifically,
we examined the ways in which scores from the 2 measures relate to one another,
as well as similarities versus differences in the ways they predict external
variables of interest (e.g., family functioning, parenting, and youth adjustment)
that acculturation is known to influence. Findings indicate distinct patterns of
results for the 2 measures. For instance, though the BIQ-S focuses entirely on
language use and other cultural practices, the ARSMA-II more consistently relates
to language variables. Further, adolescent BIQ-S cultural heritage scores related
negatively to risks for and engagement in alcohol use-supporting prior findings
whereas ARSMA-II scores were unrelated to alcohol use. Given the largely
nonoverlapping set of relationships of the BIQ-S and the ARSMA-II subscale scores
with measures of language dominance and conflict, measures of parenting, and
measures of youth outcomes, we recommend that studies utilize both of these
measures to fully appraise acculturation in this population. (PsycINFO Database
Record
PMID- 28504538
TI - Self-efficacy for coping with cancer: Revision of the Cancer Behavior Inventory
(Version 3.0).
AB - Based on self-regulation and self-efficacy theories, the Cancer Behavior
Inventory (CBI; Heitzmann et al., 2011; Merluzzi & Martinez Sanchez, 1997;
Merluzzi, Nairn, Hegde, Martinez Sanchez, & Dunn, 2001) was developed as a
measure of self-efficacy strategies for coping with cancer. In the latest
revision, CBI-V3.0, a number of psychometric and empirical advances were made:
(a) the reading level was reduced to 6th-grade level; (b) individual interviews
and focus groups were used to revise items; (c) a new spiritual coping subscale
was added; (d) data were collected from 4 samples (total N = 1,405) to conduct an
exploratory factor analysis with targeted rotation, 2 confirmatory factor
analyses, and differential item functioning; (e) item trimming was used to reduce
the total number to 27; (f) internal consistency and test-retest reliability were
computed; and (g) extensive validity testing was conducted. The results, which
build upon the strengths of prior versions, confirm a structurally and
psychometrically sound and unbiased measure of self-efficacy strategies for
coping with cancer with a reduced number of items for ease of administration. The
factors include Maintaining Activity and Independence, Seeking and Understanding
Medical Information, Emotion Regulation, Coping With Treatment Related Side
Effects, Accepting Cancer/Maintaining a Positive Attitude, Seeking Social
Support, and Using Spiritual Coping. Internal consistency (alpha = .946), test
retest reliability (r = .890; 4 months), and validity coefficients with a variety
of relevant measures indicated strong psychometric properties. The new 27-item
CBI-V3.0 has both research utility and clinical utility as a screening and
treatment-planning measure of self-efficacy strategies for coping with cancer.
(PsycINFO Database Record
PMID- 28504539
TI - Identification of questionable data using validity indices and item response
theory methods: Examinations with a teacher-rating scale.
AB - To assess quality, psychological instruments often include additional scales or
validity indices to alert users to the presence of questionable data. Although
identified cases are often scrutinized further or removed, it is not fully
understood how such cases may affect overall analyses if retained. Using a
teacher-report instrument of child behavior, this study examined 5 different
validity indices: F-Index, Consistency Index, Response Pattern Index, Rasch
Outfit, and Rasch Infit. Results showed that methods largely did not identify
similar cases. Removing flagged cases did not have a great effect on reliability
estimates or validity coefficients. Hierarchical linear modeling illustrated that
differences in validity indices were significantly related to years of teaching
experience and level of education for the F-Index. In general, before using
social-emotional screeners, teacher training may be useful to help minimize
response effects. (PsycINFO Database Record
PMID- 28504540
TI - Meta-analysis of cognitive-behavioral treatments for adult ADHD.
AB - OBJECTIVE: We conducted a meta-analysis of cognitive-behavioral treatment (CBT)
studies for adult attention-deficit/hyperactivity disorder (ADHD), examining
effects versus control and effects pre-to-post treatment to maximize the clinical
and research utility of findings from this growing literature. METHOD: Eligible
studies tested adults meeting criteria for Diagnostic and Statistical Manual of
Mental Disorders ADHD as determined by interview or using a standardized rating
scale and measured ADHD symptoms or related impairment at baseline and
posttreatment. We analyzed data from 32 studies from published and unpublished
sources available through December 2015. Effect size calculations included up to
896 participants. RESULTS: Using a random effects model, we found that CBTs had
medium-to-large effects from pre- to posttreatment (self-reported ADHD symptoms:
g = 1.00; 95% confidence interval [CI: 0.84, 1.16]; self-reported functioning g =
.73; 95% CI [0.46, 1.00]) and small-to-medium effects versus control (g = .65;
95% CI [0.44, 0.86] for symptoms, .51; 95% CI [0.23, 0.79] for functioning).
Effect sizes were heterogeneous for most outcome measures. Studies with active
control groups showed smaller effect sizes. Neither participant medication status
nor treatment format moderated pre-to-post treatment effects, and longer
treatments were not associated with better outcomes. CONCLUSIONS: Current CBTs
for adult ADHD show comparable effect sizes to behavioral treatments for children
with ADHD, which are considered well-established treatments. Future treatment
development could focus on identifying empirically supported principles of
treatment-related change for adults with ADHD. We encourage researchers to report
future findings in a way that is amenable to meta-analytic review. (PsycINFO
Database Record
PMID- 28504541
TI - Interpersonal pathoplasticity and trajectories of change in routine adolescent
and young adult residential substance abuse treatment.
AB - BACKGROUND: Partnerships between mental health care stakeholders provide a
context for generalizable clinical research with implications for quality
improvement. In the context of a partnership between an adolescent residential
substance abuse disorder (SUD) treatment center and clinical researchers,
stakeholders identified knowledge gaps (internal and the field broadly) with
regard to patient interpersonal factors that influence working alliance and acute
SUD residential treatment outcome trajectories. OBJECTIVE: To (a) examine
interpersonal pathoplasticity and identify interpersonal subtypes in a
naturalistic sample of adolescent and young-adult patients presenting for routine
residential SUD treatment and (b) investigate the association between identified
interpersonal subtypes and working alliance and acute treatment outcome
trajectories. METHOD: N = 100 patients (Mage = 17.39 years, 68% male, 84% White)
completed self-reports of symptom and functioning outcomes, interpersonal
problems, and the working alliance on multiple occasions between admission and
discharge. Multiple methods were used to identify interpersonal subtypes and test
pathoplasticity. Interpersonal subtype was entered as a predictor in respective
multilevel models of working alliance and symptom outcome. RESULTS: Interpersonal
subtypes of vindictive and exploitable patients demonstrated pathoplasticity.
Subtype did not predict working alliance trajectories; however, a significant
interaction between interpersonal subtype and a quadratic effect for time
demonstrated that exploitable patients with longer than average treatment lengths
experienced attenuated symptom change over the course of treatment whereas
vindictive patients appeared to demonstrate steady progress. CONCLUSIONS:
Interpersonal assessments should be integrated into residential SUD treatment to
identify patients with an exploitable interpersonal style who might require
additional attention or alternative interventions. (PsycINFO Database Record
PMID- 28504543
TI - Clear Cell Renal Cell Carcinoma: Identifying the Loss of the Y Chromosome on
Multiphasic MDCT.
AB - OBJECTIVE: The objective of our study was to investigate whether multiphasic MDCT
enhancement can help identify clear cell renal cell carcinomas (RCCs) with the
loss of the Y chromosome. MATERIALS AND METHODS: We derived a cohort of 43 clear
cell RCCs in men who underwent preoperative four-phase renal mass MDCT from
October 2000 to August 2013. Each lesion was segmented in its entirety on axial
images. A computer-assisted detection algorithm selected a 0.5-cm-diameter region
of maximal attenuation within each lesion in each phase. A 0.5-cm-diameter ROI
was manually placed on uninvolved renal cortex in each phase. The relative
attenuation of each lesion was calculated as follows: [(maximal lesion
attenuation - cortex attenuation) / cortex attenuation] * 100. Absolute
attenuation and relative attenuation in each phase were compared using t tests.
RESULTS: Both clear cell RCCs with the loss of the Y chromosome and clear cell
RCCs without the loss of the Y chromosome exhibited peak enhancement in the
corticomedullary phase. However, relative nephrographic attenuation of clear cell
RCCs with the loss of Y was significantly less than that of clear cell RCCs
without the loss of Y (mean, -8.9 vs 8.4 respectively; p = 0.013). A relative
nephrographic attenuation threshold of -1.6 identified the loss of Y with an
accuracy of 70% (30/43), sensitivity of 73% (16/22), and specificity of 67%
(14/21). CONCLUSION: Multiphasic MDCT enhancement may assist in identifying the
loss of the Y chromosome in clear cell RCCs; this result should be validated in a
large prospective trial.
PMID- 28504545
TI - Detection of Hemodynamically Significant Coronary Artery Stenosis With CT
Enhancement Ratio: A Validation Study in a Porcine Model.
AB - OBJECTIVE: Although numerous techniques that are based on CT number analysis have
been proposed, the assessment of hemodynamically significant coronary artery
stenosis remains a great challenge. The purpose of this study is to validate use
of the CT enhancement ratio in the detection of hemodynamically significant
coronary artery stenosis in a porcine model. MATERIALS AND METHODS: Experiments
involving eight closed-chest swine were performed. A balloon catheter was placed
into the left anterior descending coronary artery to simulate different degrees
of luminal stenosis. The myocardial blood flow (MBF) ratio was measured using the
colored microsphere technique. The fractional flow reserve was measured using an
invasive pressure wire. CT scans were performed during the first-pass phase,
while the pigs were undergoing adenosine stress tests. The CT enhancement ratio
and the CT attenuation ratio were calculated using data from the CT images
obtained. RESULTS: Results suggested that the CT enhancement ratio had a strong
correlation (y = 0.07245 + 0.09963x; r2 = 0.898; p < 0.001) with the MBF ratio
measured using the microsphere technique, whereas only moderate correlation (y =
1.5508 + 2.2684x; r2 = 0.498; p < 0.001) was noted between the CT attenuation
ratio and the MBF ratio measured using the microsphere technique. In ROC curve
analysis, the AUC values of the CT enhancement ratio and the CT attenuation ratio
were 0.927 and 0.829, respectively, with regard to the detection of significant
ischemia during adenosine stress tests, as defined by the fractional flow
reserve. CONCLUSION: The CT enhancement ratio provides a reliable prediction of
the MBF ratio measured using the microsphere technique, indicating that this
metric has good diagnostic performance in the detection of hemodynamically
significant coronary artery stenosis. The CT enhancement ratio may have potential
for use as an imaging biomarker for the relative quantitative assessment of
myocardial perfusion.
PMID- 28504542
TI - Do changes in trauma-related beliefs predict PTSD symptom improvement in
prolonged exposure and sertraline?
AB - OBJECTIVE: Negative trauma-related belief change has been found to predict
subsequent improvement in symptoms of posttraumatic stress disorder (PTSD) in
prolonged exposure (PE) and other therapies, consistent with several
psychological theories of treatment change (e.g., Foa & Kozak, 1986). However,
belief change has not been examined in selective serotonin reuptake inhibitors
such as sertraline. We examined processes associated with symptom improvement in
2 treatments for PTSD, hypothesizing that belief change would robustly predict
PTSD improvement in patients treated with PE but not those treated with
sertraline, reflecting moderation by treatment. METHOD: Patients with chronic
PTSD (N = 134; 78% women, 71.6% Caucasian, M = 38.1 years, SD = 11.8) received 10
weeks of PE or sertraline in a randomized, controlled trial. Patients reported
PTSD and depression symptoms, and trauma-related beliefs (Post-Traumatic
Cognitions Inventory; Foa, Ehlers, Clark, D Tolin, & Orsillo, 1999) at
pretreatment, every treatment session, and posttreatment. RESULTS: Using time
lagged mixed regression models, change in trauma-related beliefs predicted
subsequent PTSD symptom improvement, an effect moderated by treatment and
particularly strong in PE (d = 0.93) compared with sertraline (d = 0.35). Belief
change also predicted depressive symptom improvement but more modestly and
bidirectionally, with no difference by treatment modality. CONCLUSIONS: Trauma
related belief change precedes PTSD improvement more robustly in PE than in
sertraline and with greater specificity compared with depressive symptoms. These
findings highlight potentially divergent processes contributing to symptom change
in these PTSD treatments, with belief change as a key mechanism of PE. (PsycINFO
Database Record
PMID- 28504546
TI - Use of a 3D-Printed Abdominal Compression Device to Facilitate CT Fluoroscopy
Guided Percutaneous Interventions.
AB - OBJECTIVE: The purpose of this article is to describe a handheld external
compression device used to facilitate CT fluoroscopy-guided percutaneous
interventions in the abdomen. CONCLUSION: The device was designed with computer
aided design software to modify an existing gastrointestinal fluoroscopy
compression device and was constructed by 3D printing. This abdominal compression
device facilitates access to interventional targets, and its use minimizes
radiation exposure of radiologists. Twenty-one procedures, including biopsies,
drainage procedures, and an ablation, were performed with the device. Radiation
dosimetry data were collected during two procedures.
PMID- 28504544
TI - Radial Ultrashort TE Imaging Removes the Need for Breath-Holding in Hepatic Iron
Overload Quantification by R2* MRI.
AB - OBJECTIVE: The objective of this study is to evaluate radial free-breathing (FB)
multiecho ultrashort TE (UTE) imaging as an alternative to Cartesian FB multiecho
gradient-recalled echo (GRE) imaging for quantitative assessment of hepatic iron
content (HIC) in sedated patients and subjects unable to perform breath-hold (BH)
maneuvers. MATERIALS AND METHODS: FB multiecho GRE imaging and FB multiecho UTE
imaging were conducted for 46 test group patients with iron overload who could
not complete BH maneuvers (38 patients were sedated, and eight were not sedated)
and 16 control patients who could complete BH maneuvers. Control patients also
underwent standard BH multiecho GRE imaging. Quantitative R2* maps were
calculated, and mean liver R2* values and coefficients of variation (CVs) for
different acquisitions and patient groups were compared using statistical
analysis. RESULTS: FB multiecho GRE images displayed motion artifacts and
significantly lower R2* values, compared with standard BH multiecho GRE images
and FB multiecho UTE images in the control cohort and FB multiecho UTE images in
the test cohort. In contrast, FB multiecho UTE images produced artifact-free R2*
maps, and mean R2* values were not significantly different from those measured by
BH multiecho GRE imaging. Motion artifacts on FB multiecho GRE images resulted in
an R2* CV that was approximately twofold higher than the R2* CV from BH multiecho
GRE imaging and FB multiecho UTE imaging. The R2* CV was relatively constant over
the range of R2* values for FB multiecho UTE, but it increased with increases in
R2* for FB multiecho GRE imaging, reflecting that motion artifacts had a stronger
impact on R2* estimation with increasing iron burden. CONCLUSION: FB multiecho
UTE imaging was less motion sensitive because of radial sampling, produced
excellent image quality, and yielded accurate R2* estimates within the same
acquisition time used for multiaveraged FB multiecho GRE imaging. Thus, FB
multiecho UTE imaging is a viable alternative for accurate HIC assessment in
sedated children and patients who cannot complete BH maneuvers.
PMID- 28504547
TI - Site-Specific Onset of Low Bone Density and Correlation of Bone Turnover Markers
in Exclusive Breastfeeding Mothers.
AB - PURPOSE: Lactation often affects calcium metabolism and induces bone loss.
Calcium supplementation and a high calcium diet are recommended to prevent bone
loss, especially during inadequate calcium intake. Our study aimed at determining
bone loss in breastfeeding mothers, and if it occurred, whether it was site
specific and there were correlations between serum bone turnover markers.
MATERIALS AND METHODS: Since the 6-month exclusive breastfeeding is usually
recommended in several countries, our study examined bone mineral density (BMD)
in early (1-2 month), mid (3-4 month)-, and late (5-6 month) lactation compared
with nonpregnant, nonlactating control women. Site-specific bone loss was
monitored in lumbar vertebrae and femora. Bone turnover markers, that is, C
terminal telopeptide of type 1 collagen and N-terminal propeptide of type 1
collagen (P1NP), were determined by electrochemiluminescence immunoassays.
RESULTS: The onset of bone loss in exclusive breastfeeding mothers was site
specific, for example, in the lumbar bone at mid-lactation and in the femoral
bone in late lactation. Serum ionized calcium levels in late lactation were lower
than the normal levels. In addition, a correlation was found between bone
turnover marker, P1NP, and femoral BMD. CONCLUSIONS: The onset of bone loss in
exclusive breastfeeding mothers was site specific, and the lumbar bone was a
vulnerable and perhaps better representative site for bone loss detection. It was
suggested that the optimal starting time for calcium supplementation should be
before the mid-lactation when the bone loss was observed. In addition, the
biochemical marker that best predicted the onset of bone loss in lactating women
was P1NP.
PMID- 28504548
TI - The Lumbar Neural Foramen and Transforaminal Epidural Steroid Injections: An
Anatomic Review With Key Safety Considerations in Planning the Percutaneous
Approach.
AB - OBJECTIVE: The purpose of this article is to review the anatomy of the lumbar
neural foramen and to describe techniques of transforaminal epidural steroid
injections with emphasis on safety. Rare cases of paraplegia have been reported.
CONCLUSION: Although no consensus currently exists about which approach is the
safest, knowledge of the foraminal anatomy is a key consideration when choosing a
needle approach for transforaminal epidural steroid injections.
PMID- 28504549
TI - Determination of naloxegol in human biological matrices.
AB - AIM: Naloxegol is an oral peripherally acting MU-opioid receptor antagonist
approved for the treatment of opioid-induced constipation. Sensitive, robust,
bioanalytical methods were required to quantitate naloxegol in human biological
matrices as part of the clinical development program. METHODOLOGY/RESULTS:
Analytical plasma samples were prepared using Solid Phase Extraction (SPE)
coupled with concentration. The method's linearity was established at 0.1-50
ng/ml with up to 100-fold dilution. Urine samples were analyzed directly
postdilution; dialysate samples were extracted by supported liquid extraction.
Sensitive liquid chromatography/mass spectrometry (LC-MS/MS) assays were
developed and validated, and demonstrated acceptable precision, accuracy and
selectivity for naloxegol in the appropriate matrices. CONCLUSION: Methods for
quantifying naloxegol in human biological matrices have been successfully
validated.
PMID- 28504551
TI - Memorial-Wilma C. Diner.
PMID- 28504550
TI - Liver Abscesses: Factors That Influence Outcome of Percutaneous Drainage.
AB - OBJECTIVE: The purpose of this study was to identify the details of percutaneous
catheter drainage (PCD) of pyogenic liver abscesses, the etiologic factors, and
the management techniques that contribute to successful treatment. MATERIALS AND
METHODS: The records of 75 consecutively registered patients who underwent PCD of
96 abscesses at a single institution between May 2009 and May 2014 were
retrospectively reviewed. Thirty-nine patients (52%) were oncology patients, and
36 (48%) had recently undergone abdominal surgery. Primary success was defined as
abscess healing with the primary PCD intervention and 30-day postdrainage
survival. Salvage success was defined as abscess healing with follow-up secondary
PCD placement for symptomatic hepatic satellite collections or for clinical
recurrence. Catheter adjustments were performed during follow-up to optimize
existing drains. Univariate, multivariate, and general linear mixed model
analyses were performed. The median follow-up time after catheter removal was 6
months (range, 2-62 months). RESULTS: Drains were primarily successful in 54
patients (72%), and 17 patients (23%) needed salvage PCD; thus, overall success
was achieved in 71 patients (95%). The other four patients (5%) died of sepsis.
The primary success rate was reduced in patients with unresectable malignancies
(p = 0.01), multiple abscesses (p = 0.01), and output >= 15 mL/d at catheter
endpoint (n = 7, p = 0.001). Only unresectable malignancies had slightly lower
overall success. Large abscesses (> 150 cm3) required more catheter adjustments
and longer drainage duration to reach abscess cavity closure. Successfully
drained abscesses reached cavity closure a mean of 23 days (95% CI, 20-27 days)
after treatment. CONCLUSION: PCD was effective first-line treatment of
complicated pyogenic liver abscesses, which often require catheter adjustment and
salvage drainage procedures to reliably achieve success.
PMID- 28504552
TI - Validation of electrochemiluminescence assays for highly sensitive and
reproducible quantification of alpha-synuclein in cerebrospinal fluid.
AB - AIM: alpha-Synuclein (aSyn), a putative cerebrospinal fluid biomarker, may
support the diagnosis of neurodegenerative diseases. Previous studies led to
conflicting results due to different preanalytical and analytical procedures.
Standardized assays are required to allow for comparison of results from
different laboratories. MATERIALS & METHODS: We performed a side-by-side
validation of a commercially available (MSD, MD, USA) and a 'homebrew' assay for
quantification of aSyn according to published guidelines. RESULTS: The data
showed high sensitivity and reproducibility for both assays. Preanalytical and
analytical parameters did not affect the outcome of measurements. CONCLUSION: We
conclude that both assays are very close in performance and suitable for research
application of cerebrospinal fluid aSyn.
PMID- 28504553
TI - AAVS1-Targeted Plasmid Integration in AAV Producer Cell Lines.
AB - Adeno-associated virus (AAV) producer cell lines are created via transfection of
HeLaS3 cells with a single plasmid containing three components (the vector
sequence, the AAV rep and cap genes, and a selectable marker gene). As this
plasmid contains both the cis (Rep binding sites) and trans (Rep protein encoded
by the rep gene) elements required for site-specific integration, it was
predicted that plasmid integration might occur within the AAVS1 locus on human
chromosome 19 (chr19). The objective of this study was to investigate whether
integration in AAVS1 might be correlated with vector yield. Plasmid integration
sites within several independent cell lines were assessed via Southern,
fluorescence in situ hybridization (FISH) and PCR analyses. In the Southern
analyses, the presence of fragments detected by both rep- and AAVS1-specific
probes suggested that for several mid- and high-producing lines, plasmid DNA had
integrated into the AAVS1 locus. Analysis with puroR and AAVS1-specific probes
suggested that integration in AAVS1 was a more widespread phenomenon. High
producing AAV2-secreted alkaline phosphatase (SEAP) lines (masterwell 82 [MW82]
and MW278) were evaluated via FISH using probes specific for the plasmid, AAVS1,
and a chr19 marker. FISH analysis detected two plasmid integration sites in MW278
(neither in AAVS1), while a total of three sites were identified in MW82 (two in
AAVS1). An inverse PCR assay confirmed integration within AAVS1 for several mid-
and high-producing lines. In summary, the FISH, Southern, and PCR data provide
evidence of site-specific integration of the plasmid within AAVS1 in several AAV
producer cell lines. The data also suggest that integration in AAVS1 is a general
phenomenon that is not necessarily restricted to high producers. The results also
suggest that plasmid integration within the AAVS1 locus is not an absolute
requirement for a high vector yield.
PMID- 28504554
TI - How is patient care for multiple myeloma advancing?
AB - INTRODUCTION: Treatment of multiple myeloma has undergone profound changes in the
past years thanks to the increased understanding of the biology of the disease
and the new treatment options. New drugs and effective approaches are currently
available for the treatment of multiple myeloma, including immunomodulatory
agents, proteasome inhibitors and autologous stem cell transplantation. Areas
covered: We have described the recent updated criteria to start treatment in
multiple myeloma and summarized clinical data from major studies including most
recent agents. Particularly, results with pomalidomide, carfilzomib, ixazomib,
monoclonal antibodies such as elotuzumab, daratumumab, and checkpoint inhibitors
have been reported. Both transplant and non-transplant settings have been
covered. Expert commentary: Despite the successful improvement in overall
survival and time to relapse, multiple myeloma still remains incurable.
Therefore, there is still an unmet need for new treatment strategies with novel
mechanisms of action, like monoclonal antibodies, novel immunomodulators, and
novel proteasome inhibitors. Implementation of these novel drugs in rationally
designed therapies with a good balance of efficacy and safety should be carefully
considered in order to improve outcome.
PMID- 28504556
TI - Evolution of Technique in Laparoscopic Donor Nephrectomy: A Single Center
Experience.
AB - BACKGROUND: Renal transplantation is the most successful therapy for improving
survival and quality of life for end-stage renal disease (ESRD). Living donor
kidney transplantation (LDKTx) has been used as an alternative to reduce the stay
on the waiting list of patients with ESRD. Laparoscopic donor nephrectomy (LDN)
has become the standard procedure for LDKTx. OBJECTIVE: This study aims to
describe evolution of surgical technique with LDN at our institute. MATERIALS AND
METHODS: We retrospectively analyzed our experience with LDN performed from
January, 2003 to November, 2016, focusing on describing modifications of the
surgical technique and devices made during those years. Demographics, operative
factors, and postoperative complications of donors were reviewed. RESULTS: From
the beginning of our experience with LDKTx we have performed 185 cases. From 2003
to 2016, 144 LDN were performed. Modifying our technique in response to the
learning curve, complications encountered, and technological advancements, we
experienced low complication rates. CONCLUSIONS: Continual refinement with LDN
techniques based on intraoperative observations and technological advances is
necessary to keep complication rates low and reduce donor morbidity and time for
recovery.
PMID- 28504555
TI - Frequency and characteristics of infusion reactions during biosimilar infliximab
treatment in inflammatory bowel diseases: results from Central European
nationwide cohort.
AB - BACKGROUND: Safety data of the 'real life' use of an infliximab biosimilar, CT
P13 in inflammatory bowel disease (IBD) are still lacking. Our aim was to assess
the frequency and characteristics of infusion reactions during CT-P13 therapy in
13 Hungarian and 1 Czech IBD centres. METHODS: Clinical and safety data was
registered at fixed appointments. Trough levels and anti-drug antibody (ADA)
concentration were measured by ELISA. Association between demographic, clinical,
laboratory parameters and infusion reaction rates were evaluated statistically.
RESULTS: Three hundred and eighty-four IBD patients were included. Twenty-eight
Hungarian IBD patients (9.6%) developed infusion reaction during the treatment,
64.3% of them was previously exposed to anti TNF therapy. No infusion reaction
occurred in the Czech population. CT-P13 therapy had to be stopped in 17 patients
who developed infusion reaction and was switched to adalimumab in 12 patients.
However in 39.3% of patients developing infusion reaction CT-P13 therapy was
continued with the use of premedication. Cumulative ADA positivity rates were
8.7%, 19.3%, and 28.0% at weeks 0, 14, and 30. Previous anti-TNF-alpha exposure
(30% vs. 3.1%, p < 0.001, OR 6.3 (2.7-14.6)) and ADA positivity (32.6% vs. 4.1%,
p < 0.001, OR 19(5-73)) during the induction therapy were predictive factors for
infusion reactions. CONCLUSIONS: Patients with previous exposure to anti-TNF
alpha and ADA positivity during the induction therapy were more likely to develop
infusion reactions.
PMID- 28504558
TI - Nanoformulated water-soluble paclitaxel to enhance drug efficacy and reduce
hemolysis side effect.
AB - Surgery, chemotherapy, and radiotherapy are the three top cancer treatment
modalities. Paclitaxel (PTX) is one of the most widely used chemotherapy drugs.
However, its clinical applications have been significantly limited due to: (i)
serious hemolysis effect of currently available commercial paclitaxel
formulations and (ii) its water insolubility. An easy way to deliver paclitaxel
by a new nanocarrier system using pluronic copolymers of P123/F68 and Sorbitan
monopalmitate (Span 40) was reported in our previous research article. The
characterization of the formulation and analysis of drug release and cellular
uptake were also presented. In this article, we reported discoveries of our
follow-up in vivo antitumor and in vitro hemolytic study discoveries. The
experimental results showed that the nanoformulated PTX achieved much better
tumor suppression performance while reducing hemolysis side effects. This newly
formulated drug can significantly improve patient outcomes in cancer
chemotherapy.
PMID- 28504557
TI - Carotid angioplasty-assisted mechanical thrombectomy without urgent stenting may
be a better option in acute tandem occlusions.
AB - Background The aim of the study was to assess the efficacy of balloon angioplasty
assisted mechanical thrombectomy without urgent stenting in the carotid artery as
another approach for endovascular treatment of tandem occlusions. Methods Fifteen
consecutive cases of tandem occlusions treated with the endovascular approach
between January 2014 and May 2016 were reviewed. The study cohort included
patients with an etiology of large vessel atherosclerosis. Extracranial carotid
stenting was performed in another session if post-thrombectomy mRS modified
Rankin Score (mRS) was 0-2. Good clinical outcome was determined by follow-up at
7-10, 30 and 90 days according to the mRS. Results Most patients (80%) were male.
Eight (53.4%) patients received intravenous thrombolysis before angiography.
Proximal revascularization was successful in 100% of cases with balloon
angioplasty internal carotid artery (ICA) origin. Successful recanalization
(modified thrombolysis in cerebral infarction (mTICI) 2b-3) (mTICI 2 b-3)
occurred in 12 cases (80%) and good clinical outcomes were achieved in 10
patients (66.7%). Cervical ICA stent placement was performed in 10 patients with
good clinical outcomes. No symptomatic intracranial hemorrhage occurred after
delayed ICA stenting Conclusions This is the first reported case series to
evaluate this approach for endovascular treatment of tandem occlusions. Carotid
angioplasty-assisted mechanical thrombectomy without urgent stenting seems to be
a safer approach.
PMID- 28504559
TI - Immobilization of native type I collagen on polypropylene fabrics as a substrate
for HepG2 cell culture.
AB - Background/aims The critical part of a bio-artificial liver device is
establishment of a bioreactor filled with liver cells. However, it is still
unclear how to maintain benign cell function while achieving the sufficient cell
quantity. In the current study, we aim to establish a novel carrier for the
culture of HepG2 cells, a liver cell line, by modifying polypropylene nonwoven
fabrics with native type I collagen. Methods "Piranha" solution, KH-550 and
glutaraldehyde subsequently were used to bridge native type I collagen and
polypropylene nonwoven fabrics. The type I collagen-coupled polypropylene
nonwoven fabric was characterized by XPS, SEM, ATR-FTIR and water contact angle
measurement. Furthermore, the biocompatibility between HepG2 cells and fiber film
is evaluated by the ability of cell proliferation, albumin secretion, as well as
urea synthesis. Results The coating of collagen onto polypropylene fabrics was
more efficient using the chemical covalent binding method than direct immersion,
which was validated by the presence of collagen-related elements and chemical
bond. The adding of collagen in polypropylene fabrics promoted hydrophilicity and
HepG2 cell adherence. Additionally, enhanced cell proliferation, increased
albumin secretion and urea synthesis were observed in HepG2 cells growing on
collagen-coated polypropylene fabrics. Conclusions The collagen coated
polypropylene nonwoven fabrics, acting as a feasible substrate for HepG2 cell
culture, may be used as a promising liver cell carrier for artificial liver
reactor.
PMID- 28504560
TI - Small RNA Functions Are Required for Growth and Development of Magnaporthe
oryzae.
AB - RNA interference (RNAi) is conserved in eukaryotic organisms, and it has been
well studied in many animal and plant species and some fungal species, yet it is
not well studied in fungal plant pathogens. In the rice blast fungus Magnaporthe
oryzae, we examined small RNA (sRNA) and their biogenesis in the context of
growth and pathogenicity. Through genetic and genomic analyses, we demonstrate
that loss of a single gene encoding Dicer, RNA-dependent RNA polymerase, or
Argonaute reduces sRNA levels. These three proteins are required for the
biogenesis of sRNA-matching genome-wide regions (coding regions, repeats, and
intergenic regions). The loss of one Argonaute reduced both sRNA and fungal
virulence on barley leaves. Transcriptome analysis of multiple mutants revealed
that sRNA play an important role in transcriptional regulation of repeats and
intergenic regions in M. oryzae. Together, these data support that M. oryzae sRNA
regulate developmental processes including, fungal growth and virulence.
PMID- 28504561
TI - Sexual Violence and Intimate Partner Violence in College Women with a Mental
Health and/or Behavior Disability.
AB - OBJECTIVES: We address questions about (1) how college women with a disability
experience sexual violence (SV) and intimate partner violence (IPV) across
partners, including disability-specific abuse and (2) how SV/IPV impacts
psychological, behavioral, physical, and academic life domains. METHODS/DESIGN:
Twenty-seven female college students (mean age, 21.2; 66.6% white; 66.6%
heterosexual) were randomly sampled from university registrar records. To be
eligible for the study, students had to have at least one experience of SV/IPV
since age 18 and a disability (88.8% reported one or more mental health
conditions; 11.1% reported other conditions, such as attention deficit and
hyperactivity disorder; with the majority of women indicating their disability
preceded SV/IPV victimization). Using the Centers for Disease Control and
Prevention's definitions of SV/IPV as guides, clinically trained master's level
interviewers conducted semistructured interviews to ascertain SV/IPV patterns
across students' three most recent relationships and related life impacts.
RESULTS: SV/IPV was pervasive in college women with a disability, within hookup
settings and/or recurring SV/IPV with a long-term partner. For some women, SV
spanned multiple abusive partners. For women in relationships marked by chronic
abuse, in addition to SV, the relationship dynamic included disability-specific
abuse, social isolation, threats/intimidation, and technology-related abuse. For
women experiencing SV events within hookup settings, alcohol was a common
facilitator, with some abusers using a disability to manipulate a sexual
connection. All but one participant reported exacerbated adverse mental health
consequences (e.g., depression, anxiety, post-traumatic stress disorder, suicidal
ideation/attempts, stress) after victimization. These adverse mental health
consequences coincided with adverse behavioral (e.g., becoming less social,
avoiding usual study lounge areas on campus), physical (e.g., problems sleeping,
bruising, pregnancy concerns, and sexually transmitted disease), and academic
outcomes (e.g., skipping and/or dropping class, grades suffering). DISCUSSION:
Our results underscore the need for continued investment in campus programs that
improve response to SV/IPV, including prevention programs and support services
tailored to the specific needs and vulnerabilities of women with underlying
mental health conditions.
PMID- 28504562
TI - The animacy advantage for free-recall performance is not attributable to greater
mental arousal.
AB - People often demonstrate better memory for animate concepts (e.g., lion and
sailor) than for inanimate concepts (e.g., hammer and mountain). Researchers have
attributed this effect to an adaptive memory mechanism that favours information
relevant for survival, including information about living things. In the present
experiment, we examined the hypothesis that people demonstrate better free-recall
performance for animate than inanimate words because animate words tend to be
associated with greater mental arousal than inanimate words, a factor that was
not controlled for in previous experiments on this topic. To this end, we matched
animate and inanimate word lists on mental arousal (and several other factors),
and compared participants' free-recall performance for the two word types. We
were able to replicate past findings that participants' free-recall of animate
words exceeds their free-recall of inanimate words, but we found no support for
the possibility that the effect stems from differences in mental arousal between
animate and inanimate concepts, as this effect maintained even when the word
lists were matched on mental arousal. The present results therefore indicate that
mental arousal cannot explain the effects of animacy on free-recall performance.
PMID- 28504564
TI - Cinematic Rendering in CT: A Novel, Lifelike 3D Visualization Technique.
AB - OBJECTIVE: The purpose of this article is to present an overview of cinematic
rendering, illustrating its potential advantages and applications. CONCLUSION:
Volume-rendered reconstruction, obtaining 3D visualization from original CT
datasets, is increasingly used by physicians and medical educators in various
clinical and educational scenarios. Cinematic rendering is a novel 3D rendering
algorithm that simulates the propagation and interaction of light rays as they
pass through the volumetric data, showing a more photorealistic representation of
3D images than achieved with standard volume rendering.
PMID- 28504565
TI - Early, intensive statin treatment reduces 'hard' cardiovascular outcomes after
acute coronary syndrome.
AB - Background Early, intensive statin treatment is the standard of care after acute
coronary syndrome (ACS). However, the benefit of this approach to prevent major
adverse cardiovascular events has been demonstrated in only one randomised,
placebo controlled trial. The Myocardial Ischemia Reduction with Aggressive
Cholesterol Lowering (MIRACL) trial demonstrated that atorvastatin 80 mg daily,
compared with placebo, reduced time to first occurrence of death, non-fatal
myocardial infarction, resuscitated cardiac arrest, or hospitalisation for
unstable angina (stroke not included) during the 16 week period following ACS.
However, there were no significant effects on individual components of the
composite endpoint except unstable angina. This led some to question whether
early, intensive statin treatment reduces 'hard' events after ACS. Aim The burden
of coronary heart disease after ACS, and therefore the efficacy of its treatment,
depends not only on the occurrence of one ischaemic event, but rather on
cumulative events experienced by patients. Accordingly, we conducted a post-hoc
analysis of the MIRACL trial to examine the effect of atorvastatin on first as
well as recurrent (i.e. total) hard cardiovascular events after ACS (death,
myocardial infarction, stroke, and resuscitated cardiac arrest). Methods and
Results In the 3086 patients who comprised the MIRACL trial, atorvastatin 80 mg
did not reduce time to first hard event compared with placebo (hazard ratio 0.89,
95% confidence interval 0.72-1.10, P = 0.27). However, atorvastatin significantly
reduced total hard events (hazard ratio 0.80, 95% confidence interval 0.66-0.97,
P = 0.03). To prevent one hard event during the 16 weeks following ACS, only 11
patient-years of treatment with atorvastatin were required. Conclusion Early,
intensive treatment with atorvastatin is an efficient intervention to reduce hard
cardiovascular events after ACS.
PMID- 28504563
TI - PET Molecular Imaging-Directed Biopsy: A Review.
AB - OBJECTIVE: The purpose of this review is to summarize the applications of PET
molecular imaging-directed biopsy of a variety of organs in the management of
various diseases with a focus on cancers. CONCLUSION: PET can yield metabolic
information at the cellular and molecular levels, and PET-directed biopsy is
playing an increasing role in the diagnosis and staging of diseases.
PMID- 28504566
TI - Influence of Lactobacillus reuteri L26 BiocenolTM on immune response against
porcine circovirus type 2 infection in germ-free mice.
AB - Probiotic bacteria are frequently used for prevention of bacterial infections of
the gastrointestinal tract, but there are only limited studies on their efficacy
against viral gut infections in animals. The aim of this study was to investigate
the effect of probiotic Lactobacillus reuteri L26 BiocenolTM on the innate and
adaptive immune responses in germ-free Balb/c mice, experimentally infected by
porcine circovirus type 2 (PCV2), which confers immunosuppressive effect. A total
of 30 six-week-old female mice were divided into 3 groups and animals in
experimental group LPCV (n=10) were inoculated with L. reuteri L26, animals in
the control group (C; n=10) and experimental group PCV (n=10) received sterile De
Man-Rogosa-Sharpe broth for 7 days. Subsequently, mice from both experimental
groups were infected with PCV2; however, mice in the control group received virus
cultivation medium (mock). Virus load in faeces, ileum and mesenteric lymph nodes
(MLN); as well as gene expression of selected cytokines, immunoglobulin A (IgA)
and polymeric Ig receptor (PIgR) in the ileum, and percentage of CD8+, CD19+ and
CD49b+CD8- cells in the MLN were evaluated. Our results showed that L. reuteri
significantly decreased the amount of PCV2 in faeces and in the ileum, and up
regulated the gene expression of chemokines, interferon (IFN)-gamma, IgA and PIgR
in the ileum. Increased IFN-gamma mRNA level was accompanied by higher proportion
of natural killer cells and up-regulated IgA and PIgR gene expressions were in
accordance with significantly higher percentage of CD19+ lymphocytes in the MLN.
These findings indicate that probiotic L. reuteri has an antiviral effect on PCV2
in the intestine which is mediated by stimulation of local gut immune response.
PMID- 28504567
TI - Effects of Lactobacillus casei CCFM419 on insulin resistance and gut microbiota
in type 2 diabetic mice.
AB - The antidiabetic effect of Lactobacillus is increasingly recognized worldwide. In
this research, the hypoglycemic activity of Lactobacillus casei CCFM419 was
investigated in mice with high-fat and low-dose streptozotocin induced type 2
diabetes. Oral L. casei CCFM419 administration favourably regulated blood glucose
balance, increased glucose tolerance and protected islets in the diabetic mice,
accompanied by an improvement in lipid metabolism. The homeostasis model of
insulin resistance, insulin level and insulin tolerance test and mRNA expression
of PI3K/Akt signalling pathway indexes revealed that L. casei CCFM419 had a
positive effect on insulin resistance. Furthermore, treatment with L. casei
CCFM419 recovered the level of short-chain fatty acids and increased the
abundance of butyrate-producing bacteria, such as Allobaculum and Bacteriodes.
These results demonstrated that L. casei CCFM419 had the potential ability to
ameliorate insulin resistance and hyperglycaemic in type 2 diabetic mice through
underlying PI3K/Akt signalling pathway and short-chain fatty acids/gut microbiota
pathways.
PMID- 28504568
TI - Lactobacillus rhamnosus CRL1505 nasal administration improves recovery of T-cell
mediated immunity against pneumococcal infection in malnourished mice.
AB - Immunobiotic lactic acid bacteria have become an interesting alternative for the
prevention of respiratory infections. Previously, we demonstrated that the nasal
administration of Lactobacillus rhamnosus CRL1505, during repletion of
malnourished mice, resulted in diminished susceptibility to the challenge with
the respiratory pathogen Streptococcus pneumoniae. Considering the known
alterations induced by malnutrition on T lymphocytes and the importance of this
cell population on the protection against respiratory pathogens, we aimed to
study the effect of L. rhamnosus CRL1505 nasal administration on the recovery of
T cell-mediated defences against pneumococcal infection in malnourished mice
under nutritional recovery. Malnourished mice received a balanced conventional
diet (BCD) for seven days or BCD for seven days with nasal L. rhamnosus CRL1505
supplementation during last two days of the treatment. After the treatments mice
were infected with S. pneumoniae. Flow cytometry studies were carried out in bone
marrow, thymus, spleen and lung to study T cells, and Th1/Th2 cytokine profiles
were determined in broncho-alveolar lavages and serum. The administration of
CRL1505 strain to malnourished mice under recovery reduced quantitative and
qualitative alterations of CD4+ T cells in the bone marrow, thymus, spleen and
lung induced by malnutrition. In addition, CRL1505 treatment augmented Th2
cytokines (interleukin 10 and 4) in respiratory and systemic compartments after
pneumococcal infection. These results show that modulation of CD4+ T lymphocytes
induced by L. rhamnosus CRL1505 has an important role in the beneficial effect
induced by this strain on the recovery of malnourished mice. These data also
indicate that nasally administered L. rhamnosus CRL1505 may represent a non
invasive alternative to modulate and improve the T cell-mediated immunity against
respiratory pathogens in immunocompromised malnourished hosts.
PMID- 28504569
TI - Comparisons for Effectiveness of Aromatherapy and Acupressure Massage on Quality
of Life in Career Women: A Randomized Controlled Trial.
AB - OBJECTIVES: This study was aimed to compare the effectiveness of aromatherapy and
acupressure massage intervention strategies on the sleep quality and quality of
life (QOL) in career women. DESIGN: The randomized controlled trial experimental
design was used in the present study. One hundred and thirty-two career women (24
55 years) voluntarily participated in this study and they were randomly assigned
to (1) placebo (distilled water), (2) lavender essential oil (Lavandula
angustifolia), (3) blended essential oil (1:1:1 ratio of L. angustifolia, Salvia
sclarea, and Origanum majorana), and (4) acupressure massage groups for a 4-week
treatment. The Pittsburgh Sleep Quality Index and Short Form 36 Health Survey
were used to evaluate the intervention effects at pre- and postintervention.
RESULTS: After a 4-week treatment, all experimental groups (blended essential
oil, lavender essential oil, and acupressure massage) showed significant
improvements in sleep quality and QOL (p < 0.05). Significantly greater
improvement in QOL was observed in the participants with blended essential oil
treatment compared with those with lavender essential oil (p < 0.05), and a
significantly greater improvement in sleep quality was observed in the
acupressure massage and blended essential oil groups compared with the lavender
essential oil group (p < 0.05). CONCLUSIONS: The blended essential oil exhibited
greater dual benefits on improving both QOL and sleep quality compared with the
interventions of lavender essential oil and acupressure massage in career women.
These results suggest that aromatherapy and acupressure massage improve the sleep
and QOL and may serve as the optimal means for career women to improve their
sleep and QOL.
PMID- 28504570
TI - Saliva: a reliable sample matrix in bioanalytics.
AB - Saliva is gaining increasing attention as a bioanalytical sample matrix. Mostly
because of the easy and noninvasive collection, it is not only beneficial in
endocrinological and behavioral science, but also in pediatrics. Saliva also has
the advantage of being the only body fluid which can be collected even during
physical exercise, for example, during sportive activities, and there are
physiological characteristics that make it superior to serum/plasma or urine for
specific scientific questions. This review provides an insight into the
physiology of saliva formation, explaining how certain compounds enter this
bodily fluid, and gives advice for collection, storage and analytical methods.
Finally, it presents a number of reliable and proven applications for saliva
analysis from scientific fields including endocrinology, sports medicine,
forensics and immunology.
PMID- 28504571
TI - The Legend of the Luschka Tubercle and Its Association With Snapping Scapulae:
Osseous Morphology of Snapping Scapulae on CT Images.
AB - OBJECTIVE: The purpose of this article is to determine the osseous morphology of
snapping scapulae on CT images. MATERIALS AND METHODS: Retrospectively, 2D and 3D
CT images of the scapulae of 35 patients with snapping scapula were compared with
35 age-matched control group subjects. Two observers analyzed the following
parameters: presence of the Luschka tubercle; abnormalities of the bones and
periscapular soft tissues; shape, thickness, and length of the superior angle of
the scapula; craniocaudal length of the scapula; minimum distance between the
scapula and rib cage; depth of the subscapular fossa; and the superomedial angle.
RESULTS: In patients with snapping scapulae, observer 1 did not find any Luschka
tubercles, whereas observer 2 detected one; in the control group both observers
found two Luschka tubercles (p > 0.49). One scapular osteochondroma was found in
the group with snapping scapulae. No further abnormalities of the rib cage or
periscapular soft tissues were found in that group. The superior angle of the
scapula was significantly thicker in the snapping scapula group compared with the
control group (4.8 +/- 1.3 mm vs 4.0 +/- 1.0 mm, p < 0.012). The subscapular
fossa was significantly deeper in patients with snapping scapula than in control
group subjects (25.7 +/- 5.2 mm vs 21.8 +/- 5.0 mm, p < 0.005). The remaining
parameters did not differ significantly between the groups. CONCLUSION: The
Luschka tubercle was rarely observed and not associated with a snapping scapula.
However, the superior angle of the scapula was significantly thicker and the
subscapular fossa was significantly deeper in patients with snapping scapula than
in control group subjects.
PMID- 28504572
TI - Screening Mammography for Women in Their 40s: The Potential Impact of the
American Cancer Society and U.S. Preventive Services Task Force Breast Cancer
Screening Recommendations.
AB - OBJECTIVE: The purpose of this study was to review screening mammograms obtained
in one practice with the primary endpoint of determining the rate of detection of
breast cancer and associated prognostic features in women 40-44 and 45-49 years
old. MATERIALS AND METHODS: The retrospective cohort study included women in
their 40s with breast cancer detected at screening from June 2014 through May
2016. The focus was on cancer detection rate, pathologic findings, and risk
factors. RESULTS: A total of 32,762 screens were performed, and 808 biopsies were
recommended. These biopsies yielded 224 breast cancers (cancer detection rate,
6.84 per 1000 screens). Women 40-49 years old had 18.8% of cancers detected; 50
59 years, 21.8%; 60-69 years, 32.6%; and 70-79 years, 21.4%. Among the 40- to 49
year-old women, women 40-44 years old underwent 5481 (16.7%) screens, had 132
biopsies recommended, and had 20 breast cancers detected (cancer detection rate,
3.6/1000). Women 45-49 years old underwent 5319 (16.2%) screens, had 108 biopsies
recommended, and had 22 breast cancers detected (cancer detection rate,
4.1/1000). Thus, women 40-44 years old had 8.9% and women 45-49 years old had
9.8% of all screen-detected breast cancers. Of these only a small percentage of
women with detected cancers had a first-degree relative with breast cancer (40-44
years, 15%; 45-49 years, 32%) or a BRCA mutation (40-44 years, 5%; 45-49 years,
5%), and over 60% of the cancers were invasive. CONCLUSION: Women 40-49 years old
had 18.8% of all screen-detected breast cancers. The two cohorts (40-44 and 45-49
years old) had similar incidences of screen-detected breast cancer (8.9%, 9.8%)
and cancer detection rates within performance benchmark standards, supporting a
similar recommendation for both cohorts and the American College of Radiology
recommendation of annual screening mammography starting at age 40.
PMID- 28504574
TI - Gut dysbiosis following C-section instigates higher colonisation of toxigenic
Clostridium perfringens in infants.
AB - Herein we investigated the intestinal carriage of alpha-toxigenic and
enterotoxigenic Clostridium perfringens during infancy, focusing on its
association with other gut microbes and mode of delivery and feeding. Faecal
samples from 89 healthy term infants were collected at age 7 days, 1 month, 3
months, 6 months and 3 years. C. perfringens was quantified by qPCR; other gut
bacteria were quantified by reverse-transcription-qPCR. Alpha-toxigenic C.
perfringens was detected in 3.4% infants at day 7 but was present in 35-40%
infants at subsequent time-points, with counts ranging from 103-107 cells/g
faeces. Enterotoxigenic C. perfringens remained undetected at day 7 but was
detected in 1.1, 4.5, 10.1 and 4.5% infants at 1 month, 3 months, 6 months and 3
years, respectively. Intriguingly, infants carrying alpha-toxigenic C.
perfringens had lower levels of Bacteroides fragilis group, bifidobacteria,
lactobacilli and organic acids as compared to non-carriers. Further analyses
revealed that, compared to vaginally-born infants, caesarean-born infants had
higher carriage of C. perfringens and lower levels of B. fragilis group,
bifidobacteria, lactobacilli and faecal organic acids during first 6 months.
Compared to formula-fed infants, breast-fed infants were slightly less often
colonised with C. perfringens; and within caesarean-born infants, breast-fed
infants had slightly lower levels of C. perfringens and higher levels of B.
fragilis group, bifidobacteria, and lactobacilli than formula-fed infants. This
study demonstrates the quantitative dynamics of toxigenic C. perfringens
colonisation in infants during the early years of life. Caesarean-born infants
acquire a somewhat perturbed microbiota, and breast-feeding might be helpful in
ameliorating this dysbiosis. Higher carriage of toxigenic C. perfringens in
healthy infants is intriguing and warrants further investigation of its sources
and clinical significance in infants, particularly the caesarean-born who may
represent a potential reservoir of this opportunistic pathogen and might be more
prone to associated illnesses.
PMID- 28504573
TI - Human Norovirus and Its Surrogates Induce Plant Immune Response in Arabidopsis
thaliana and Lactuca sativa.
AB - Human norovirus is the leading cause of foodborne illness worldwide with the
majority of outbreaks linked to fresh produce and leafy greens. It is essential
that we thoroughly understand the type of relationship and interactions that take
place between plants and human norovirus to better utilize control strategies to
reduce transmission of norovirus in the field onto plants harvested for human
consumption. In this study the expression of gene markers for the salicylic acid
(SA) and jasmonic acid (JA) plant defense pathways was measured and compared in
romaine lettuce (Lactuca sativa) and Arabidopsis thaliana Col-0 plants that were
inoculated with Murine Norovirus-1, Tulane Virus, human norovirus GII.4, or
Hank's Balanced Salt Solution (control). Genes involving both the SA and JA
pathways were expressed in both romaine lettuce and A. thaliana for all three
viruses, as well as controls. Studies, including gene expression of SA- and JA
deficient A. thaliana mutant lines, suggest that the JA pathway is more likely
involved in the plant immune response to human norovirus. This research provides
the first pieces of information regarding how foodborne viruses interact with
plants in the preharvest environment.
PMID- 28504576
TI - Is the role of human female reproductive tract microbiota underestimated?
AB - An issue that is currently undergoing extensive study is the influence of human
vaginal microbiota (VMB) on the health status of women and their neonates.
Healthy women are mainly colonised with lactobacilli such as Lactobacillus
crispatus, Lactobacillus jensenii, and Lactobacillus iners; however, other
bacteria may be elements of the VMB, particularly in women with bacterial
vaginosis. The implementation of culture-independent molecular methods in VMB
characterisation, especially next-generation sequencing, have provided new
information regarding bacterial diversity in the vagina, revealing a large number
of novel, fastidious, and/or uncultivated bacterial species. These molecular
studies have contributed new insights regarding the role of bacterial community
composition. In this study, we discuss recent findings regarding the reproductive
tract microbiome. Not only bacteria but also viruses and fungi constitute
important components of the reproductive tract microbiome. We focus on aspects
related to the impact of the maternal microbiome on foetal development, as well
as the establishment of the neonatal microbiomes, including the placenta
microbiome, and the haematogenous source of intrauterine infection. We also
discuss whether the role of the vaginal microbiome is currently understood and
appreciated.
PMID- 28504575
TI - Alleviation of enterotoxigenic Escherichia coli challenge by recombinant
Lactobacillus plantarum expressing a FaeG- and DC-targeting peptide fusion
protein.
AB - FaeG is the major subunit of K88 fimbriae. These cell surface attachments are
considered to be the major virulence factor of enterotoxigenic Escherichia coli
(ETEC), which causes diarrhoea in piglets. The use of dendritic cell-targeting
peptide (DCpep) has been demonstrated to be an effective approach to enhance the
immunity of vaccines. Lactobacillus plantarum is an attractive candidate for oral
vaccination owing to its beneficial effects and safety. In this study, L.
plantarum was employed to deliver a FaeG-DCpep fusion antigen, and the immune
response in mice was evaluated. The synthesis of FaeG-DCpep dramatically
increased the adhesion of recombinant L. plantarum (RLP) to IPEC-J2 cell
surfaces, resulting in direct competition between L. plantarum and ETEC during
adhesion assays. Significantly higher levels of body weight gain, sera
immunoglobulin G and intestinal immunoglobulin A were observed in BALB/c mice
immunised with RLP. In addition, the number of CD19+ B cells and CD11c+DC cells
and the expression levels of several cytokines in the spleen and lymph nodes
increased significantly compared to non-immunised mice. The oral administration
of RLP also alleviated the symptoms of ETEC challenge, as shown by haematoxylin
eosin staining, indicating that RLP may be an efficient vaccine candidate.
PMID- 28504577
TI - Lactobacillus fermentum IM12 attenuates inflammation in mice by inhibiting NF
kappaB-STAT3 signalling pathway.
AB - In the present study, we isolated Lactobacillus fermentum IM12 from human gut
microbiota, which strongly inhibited interleukin (IL)-6 expression and STAT3
activation in lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages,
and examined its anti-inflammatory effect in mice with carrageenan-induced hind
paw oedema (CIE) or 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis
(TIC). Oral administration of IM12 (0.2*109, 1*109 or 5*109 cfu/mouse, once a day
for 3 days) in mice with CIE significantly suppressed the increase of oedema
volume and thickness, as well as myeloperoxidase activity and IL-6, IL-17, NO,
and prostaglandin E2 levels in the carrageenan-stimulated paw. Treatment with
IM12 (1*109 cfu/mouse, once a day for 3 days) in mice with TIC significantly
suppressed colon shortening, and myeloperoxidase activity and IL-6 and IL-17
levels. Treatment with IM12 in mice with CIE or TIC also suppressed the
expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, as well as
activation of nuclear factor kappa beta (NF-kappaB) and signal transducer and
activator of transcription 3 (STAT3). Furthermore, IM12 significantly inhibited
the expression of iNOS, and COX-2, as well as activation of NF-kappaB in LPS
stimulated mouse peritoneal macrophages. The inflammatory effect of heat
inactivated IM12 was significantly different to that of live IM12 in mice with
TIC, although anti-inflammatory effect of IM12 was reduced by heat treatment.
Based on these findings, IM12 may attenuate inflammation by inhibiting NF-kappaB
STAT3 signalling pathway.
PMID- 28504578
TI - Effects of dietary chitosan on growth, lipid metabolism, immune response and
antioxidant-related gene expression in Misgurnus anguillicaudatus.
AB - This study was performed to evaluate the effects of dietary chitosan
supplementation on growth performance, lipid metabolism, gut microbial,
antioxidant status and immune responses of juvenile loach (Misgurnus
anguillicaudatus). Five experimental diets were formulated to contain graded
levels of chitosan (0 (control), 0.5, 1, 2 and 5% CHI) for 50 days. Results of
the present study showed that body weight gain was significantly higher in fish
fed chitosan supplemented diets in dose dependent manner than control group.
Increasing dietary chitosan levels reduced gut lipid content. Meanwhile the mRNA
expression levels of intestine lipoprotein lipase and fatty acid binding protein
2 were significantly reduced with incremental dietary chitosan level. The
percentages of total monounsaturated fatty acid decreased, while polyunsaturated
fatty acid increased with dietary chitosan. The fish fed 0.5% CHI had higher
mucus lysozyme activity (LZM) than those fed 0% CHI, but the LZM activity was
significantly decreased with advancing chitosan supplement. The expression levels
of superoxide dismutase, catalase and glutathione peroxidase revealed a similar
trend, where the highest expressions were found in fish fed 5% CHI diet. In the
term of intestine microbiota between 0 and 1% CHI groups, the proportion of
bacteria in the phylum Bacteroidetes increased, whereas the proportion of
bacteria in the phylum Firmicutes decreased as the fish supplemented chitosan. In
conclusion, supplementation of chitosan improved growth performance, antioxidant
status and immunological responses in loach.
PMID- 28504579
TI - Exopolysaccharide-producing Streptococcus thermophilus CRL1190 reduces the
inflammatory response caused by Helicobacter pylori.
AB - This work evaluated the ability of the probiotic Streptococcus thermophilus
CRL1190 strain and its exopolysaccharides to adhere to gastric mucosa. Probiotic
bacteria attachment to the human stomach epithelium was confirmed in human
stomach tissue samples and the gastric epithelial cell line AGS. In addition, it
was demonstrated that S. thermophilus CRL1190 strain reduced Helicobacter pylori
adhesion and attenuated inflammatory response in AGS cells. This is the first
demonstration of the capacity of S. thermophilus CRL1190 to adhere to the stomach
gastric mucosa, and improve protection against H. pylori through the reduction of
its adhesion and the modulation of the inflammatory response. Therefore, S.
thermophilus CRL1190 fermented milk is a good candidate for further in vivo
studying of the protective effect of functional food against H. pylori infection
and gastric inflammatory damage.
PMID- 28504580
TI - Intragastric administration of Lactobacillus casei BL23 induces regulatory
FoxP3+RORgammat+ T cells subset in mice.
AB - Many studies have highlighted the immunomodulatory properties of the probiotic
strain Lactobacillus casei BL23. Recently, we demonstrated the ability of this
strain to modulate the Th2-oriented immune response in a mouse model of cow's
milk allergy based on the induction of a Th17-biased immune response. The
probiotic function of L. casei has been also linked to gut-microbiota
modifications which could been potentially involved in the immune regulation;
however, its precise mechanism of action remains poorly understood. In this
regard, recent studies suggest that gut microbiota induces a specific subset of
CD4+FoxP3+ Treg cells that also express RORgammat+, the specific transcription
factor of Th17 cells. This new type of regulatory T cells, called type 3 Treg,
displays suppressive function during intestinal inflammation, participating in
inflammation control. We thus explored the ability of L. casei BL23 to
specifically induce type 3 Treg cells, both in vitro and in vivo. Our results
showed that intragastric administration of L. casei BL23 to mice induces local
and systemic FoxP3+ RORgammat+ type 3 Treg cells that could then participate in
the beneficial effects of L. casei BL23 in different intestinal-related
disorders.
PMID- 28504581
TI - Bacillus coagulans GBI-30, 6086 increases plant protein digestion in a dynamic,
computer-controlled in vitro model of the small intestine (TIM-1).
AB - The aim of this study was to assess the potential of the probiotic Bacillus
coagulans GBI-30, 6086 [GanedenBC30] (BC30) to aid in protein digestion of
alimentary plant proteins. To test this, three plant proteins, from pea, soy and
rice, were digested in a validated in vitro model of the stomach and small
intestine (TIM-1) in the absence and in the presence of BC30. Samples were taken
from the TIM-1 fractions that mimic uptake of amino acids by the host and
analysed for alpha-amino nitrogen (AAN) and total nitrogen (TN). Both were
increased by BC30 for all three plant proteins sources. The ratio of TN/AAN
indicated that for pea protein digestion was increased by BC30, but the degree of
polymerisation of the liberated small peptides and free amino acids was not
changed. For soy and rice, however, BC30 showed a 2-fold reduction in the TN/AAN
ratio, indicating that the liberated digestion products formed during digestion
in the presence of BC30 were shorter peptides and more free amino acids, than
those liberated in the absence of BC30. As BC30 increased protein digestion and
uptake in the upper gastrointestinal (GI) tract, it consequently also reduced the
amount of protein that would be delivered to the colon, which could there be
fermented into toxic metabolites by the gut microbiota. Thus, the enhanced
protein digestion by BC30 showed a dual benefit: enhanced amino acid
bioavailability from plant proteins in the upper GI tract, and a healthier
environment in the colon.
PMID- 28504582
TI - Endoscopic Clip MRI Screening: A Canada-Wide Policy Survey.
AB - OBJECTIVE: Not all endoscopically placed clips are MRI compatible, so screening
for endoscopic clips before MRI is recommended. The purpose of this study was to
assess endoscopic clip screening practices at Canadian MRI centers, including
number of centers that screen, specific screening methods, perceived safety of
endoscopic clip models, and practices for dealing with confirmed gastrointestinal
endoscopic clips. MATERIALS AND METHODS: A bilingual online survey was
distributed to Canadian MRI centers to assess site demographics, endoscopic clip
screening practices, safety considerations for different endoscopic clip models,
protocols for dealing with patients with endoscopic clips, and the perceived
value of screening. One year later, a secondary survey was distributed to the
original participants to assess for changes made to screening policy after the
initial survey and to assess awareness of any complications arising from the
presence of endoscopic clips during MRI. RESULTS: Sixty-seven MRI centers
completed the survey (55% response rate). Sixteen centers (24%) did not
specifically screen for endoscopic clips, five because they were not aware that
endoscopic clips may not be safe for MRI. Fifty-one centers (76%) did screen for
endoscopic clips. At least 23% of screeners misclassified the safety of one or
more MRI-unsafe clips. As many as 36% of screeners may perform MRI on patients
with confirmed gastrointestinal endoscopic clips; 16% reschedule for more than 6
weeks after endoscopy; and 18% limit the field strength to 1.5 T, the safety of
which is uncertain. CONCLUSION: Many Canadians are undergoing MRI without
screening for endoscopic clips. Although the risks of MRI to patients with
endoscopic clips is unclear, the misclassification of some endoscopic clip models
and inconsistent protocols for dealing with confirmed endoscopic clips call for
further research and unified evidence-based endoscopic clip screening standards.
PMID- 28504583
TI - Repeated failures to obtain selective directed forgetting in lab and online
samples and variations in stimuli.
AB - Previous research has produced mixed findings as to whether it is possible to
selectively forget a subset of items while maintaining access to the remaining
items from the same episode, using a modified version of the list-method directed
forgetting (LMDF) paradigm. The present study includes six attempts to obtain the
selective directed forgetting (SDF) effect with the aim of exploring its
underlying mechanisms. However, despite variations in the stimuli and samples,
which included both lab and online participants, we failed to obtain SDF across
five experiments. In one of the experiments, we observed what appeared to be an
SDF effect; however, the unexpected baseline differences across the conditions
make the interpretation of this result equivocal. In contrast, standard directed
forgetting effect was obtained when an LMDF condition was included in the design.
An evaluation of the previous literature in combination with the present study
raises questions about the reliability of the SDF phenomenon.
PMID- 28504584
TI - Silvanus Phillips Thompson on Perception.
PMID- 28504585
TI - Seven- to 11-Year-Olds' Developing Ability to Recognize Natural Facial
Expressions of Basic Emotions.
AB - Being able to recognize facial expressions of basic emotions is of great
importance to social development. However, we still know surprisingly little
about children's developing ability to interpret emotions that are expressed
dynamically, naturally, and subtly, despite real-life expressions having such
appearance in the vast majority of cases. The current research employs a new
technique of capturing dynamic, subtly expressed natural emotional displays
(happy, sad, angry, shocked, and disgusted). Children aged 7, 9, and 11 years
(and adults) were systematically able to discriminate each emotional display from
alternatives in a five-way choice. Children were most accurate in identifying the
expression of happiness and were also relatively accurate in identifying the
expression of sadness; they were far less accurate than adults in identifying
shocked and disgusted. Children who performed well academically also tended to be
the most accurate in recognizing expressions, and this relationship maintained
independently of chronological age. Generally, the findings testify to a well
developed ability to recognize very subtle naturally occurring expressions of
emotions.
PMID- 28504587
TI - A Single Intercostal Space Thoracoscopic Approach for Minimally Invasive Ivor
Lewis Esophagectomy.
AB - OBJECTIVE: We present a laparoscopic and single intercostal space thoracoscopic
approach (SICS group) for Ivor Lewis minimally invasive esophagectomy (MIE) and
provide postoperative analgesia with a continuous multiple intercostal nerve
blocking technique. The characters of this technique are evaluated. MATERIALS AND
METHODS: From October 2015 to April 2016, 18 consecutive patients with esophageal
cancer were treated with Ivor Lewis MIE by a SICS group. Moreover, from July 2014
to September 2015, 48 patients with esophageal cancer received Ivor Lewis MIE by
four-port video-assisted thoracic surgery (VATS) approach. Among those patients,
by using propensity-score matching, 18 matched patients who underwent four-port
VATS MIE (four-port group) were retrospectively selected for further statistical
analysis. Patient demographics, short-term postoperative outcomes were recorded.
RESULTS: None of the patients in the SICS group required conversion to an open
procedure. No failure of the intrathoracic esophagogastrostomy occurred. No
perioperative mortality or readmission was observed in this series. No patient
suffered from anastomotic leak or complained remarkable dysphasia during follow
up. SICS group had a shorter duration of both docking procedure and closure of
chest incisions compared with four-port group. The visual analog scale (VAS) pain
scores on 24 hours after surgery was significantly lower in SICS group than in
four-port group, while the values on 6 hours were comparable. The level of
creatine kinase on postoperative day (POD) 1 was significantly lower in SICS
group than in four-port group. CONCLUSION: Single intercostal space thoracoscopic
procedure is safe and technically feasible and can therefore be viewed as an
attractive alternative approach for performing Ivor Lewis MIE.
PMID- 28504588
TI - The Impact of Corruption on Population Health.
PMID- 28504591
TI - Theiler's Murine Encephalomyelitis Virus.
PMID- 28504590
TI - Winning the BIG Medals.
PMID- 28504589
TI - Analysis of Saliva Gene Expression during Head and Neck Cancer Radiotherapy: A
Pilot Study.
AB - Saliva, a biological fluid, is a promising candidate for novel approaches to
prognosis, clinical diagnosis, monitoring and management of patients with both
oral and systemic diseases. However, to date, saliva has not been widely
investigated as a biomarker for radiation exposure. Since white blood cells are
also present in saliva, it should theoretically be possible to investigate the
transcriptional biomarkers of radiation exposure classically studied in whole
blood. Therefore, we collected whole blood and saliva samples from eight head and
neck cancer patients before the start of radiation treatment, at mid-treatment
and after treatment. We then used a panel of five genes: BAX, BBC3, CDKN1A, DDB2
and MDM2, designated for assessing radiation dose in whole blood to evaluate gene
expression changes that can occur during radiotherapy. The results revealed that
the expression of the five genes did not change in whole blood. However, in
saliva, CDKN1A and DDB2 were significantly overexpressed at the end, compared to
the start, of radiotherapy, and MDM2 was significantly underexpressed between mid
treatment and at the end of treatment. Interestingly, CDKN1A and DDB2 expressions
also showed an increasing monotonic relationship with total radiation dose
received during radiotherapy. To our knowledge, these results show for the first
time the ability to detect gene expression changes in saliva after head and neck
cancer radiotherapy, and pave the way for further promising studies validating
saliva as a minimally invasive means of biofluid collection to directly measure
radiation dose escalation during treatment.
PMID- 28504592
TI - Hungers that Need Feeding: On the Normativity of Mindful Nourishment.
AB - Drawing on participant observation in a 'mindful weight loss' course offered in
the Netherlands, this paper explores the normative register through which
mindfulness techniques cast people in relation to concerns with overeating and
body weight. The women seeking out mindfulness use eating to cope with troubles
in their lives and are hindered by a preoccupation with the size of their bodies.
Mindfulness coaches aim to help them let go of this 'struggle with eating' by
posing as the central question: 'what do I really hunger after?' The self's
hungers include 'belly hunger' but also stem from mouths, hearts, heads, noses
and eyes. They cannot all be fed by food. The techniques detailed in this paper
focus on recognizing and disentangling one's hungers; developing self-knowledge
of and a sensitivity to what 'feeds' one's life; and the way one positions
oneself in relation to oneself and the world. While introducing new norms, the
course configures 'goods' and 'bads' in different ways altogether, shaping the
worlds people come to inhabit through engaging in self-care. In particular, the
hungering body is foregrounded as the medium through which life is lived. Taking
a material semiotic approach, this paper makes an intervention by articulating
the normative register of nourishment in contrast to normalization. Thus, it
highlights anthropologists' potential strengthening of different ways of doing
normativity.
PMID- 28504593
TI - Comparison Between Digital and Synthetic 2D Mammograms in Breast Density
Interpretation.
AB - OBJECTIVE: The purpose of this study was to compare assessments of breast density
on synthetic 2D images as compared with digital 2D mammograms. MATERIALS AND
METHODS: This retrospective study included consecutive women undergoing screening
with digital 2D mammography and tomosynthesis during May 2015 with a negative or
benign outcome. In separate reading sessions, three radiologists with 5-25 years
of clinical experience and 1 year of experience with synthetic 2D mammography
read digital 2D and synthetic 2D images and assigned breast density categories
according to the 5th edition of BI-RADS. Inter- and intrareader agreement was
assessed for each BI-RADS density assessment and combined dense and nondense
categories using percent agreement and Cohen kappa coefficient for consensus and
all reads. RESULTS: A total of 309 patients met study inclusion criteria.
Agreement between consensus BI-RADS density categories assigned for digital and
synthetic 2D mammography was 80.3% (95% CI, 75.4-84.5%) with kappa = 0.73 (95%
CI, 0.66-0.79). For combined dense and nondense categories, agreement reached
91.9% (95% CI, 88.2-94.7%). For consensus readings, similar numbers of patients
were shifted between nondense and dense categories (11 and 14, respectively) with
the synthetic 2D compared with digital 2D mammography. Interreader differences
were apparent; assignment to dense categories was greater with digital 2D
mammography for reader 1 (odds ratio [OR], 1.26; p = 0.002), the same for reader
2 (OR, 0.91; p = 0.262), and greater with synthetic 2D mammography for reader 3
(OR, 0.86; p = 0.033). CONCLUSION: Overall, synthetic 2D mammography is
comparable with digital 2D mammography in assessment of breast density, though
there is some variability by reader. Practices can readily adopt synthetic 2D
mammography without concern that it will affect density assessment and subsequent
recommendations for supplemental screening.
PMID- 28504594
TI - A Deep Dive into Asthma Transcriptomics. Lessons from U-BIOPRED.
PMID- 28504595
TI - It's Bad-Really Bad-But Does it Matter? Medication Adherence in Chronic
Obstructive Pulmonary Disease.
PMID- 28504596
TI - Low Lung Function in Young Adult Life Is Associated with Early Mortality.
PMID- 28504597
TI - Reply: Transpulmonary Pressure Meaning: Babel or Conceptual Evolution?
PMID- 28504598
TI - Transpulmonary Pressure Meaning: Babel or Conceptual Evolution?
PMID- 28504599
TI - Is Concomitant Use of Theophylline and Roflumilast Really Contraindicated?
PMID- 28504600
TI - Adding Pedometers to Pulmonary Rehabilitation Did Not Result in Greater Physical
Activity. An Important Answer, but What Was the Question?
PMID- 28504601
TI - What's in a Number? Platelet Count Dynamics as a Novel Mediator of Acute
Respiratory Distress Syndrome Survival.
PMID- 28504602
TI - Eosinophils: Ancient Cells with New Roles in Chronic Lung Inflammation.
PMID- 28504603
TI - Chronic Thromboembolic Pulmonary Hypertension: Part 1.
PMID- 28504604
TI - Sputum Neutrophil Elastase as a Biomarker for Disease Activity in Bronchiectasis.
PMID- 28504606
TI - Erratum: Objective Assessment of Adherence to Inhalers by Patients with Chronic
Obstructive Pulmonary Disease.
PMID- 28504605
TI - Learning Health Care System: Pragmatic Comparison of Crystalloid Choice in a
Medical Intensive Care Unit.
PMID- 28504608
TI - Interpretation of protein electrophoresis.
PMID- 28504607
TI - Innate inflammatory gene expression profiling in potential brain-dead donors:
detailed investigation of the effect of common corticosteroid therapy.
AB - Our study aimed to assess the influence of common methylprednisolone therapy on
innate inflammatory factors in potential brain-dead organ donors (BDDs). The
study groups consisted of 50 potential BDDs who received 15 mg/kg/d
methylprednisolone and 25 live organ donors (LDs) as control group. Innate
immunity gene expression profiling was performed by RT-PCR array. Soluble serum
cytokines and chemokines, complement components, heat shock protein 70 (HSP70)
and high mobility group box-1 (HMGB1) were measured by ELISA. Surface expression
of TLR2 and TLR4 were determined using flow cytometry. Gene expression profiling
revealed up-regulation of TLRs 1, 2, 4, 5, 6, 7 and 8, MYD88, NF-kappaB, NF
kappaB1A, IRAK1, STAT3, JAK2, TNF-alpha, IL-1beta, CD86 and CD14 in the BDD
group. Remarkably, the serum levels of C-reactive protein and HSP70 were
considerably higher in the BDD group. In addition, serum amounts of IL-1beta, IL
6, TNF-alpha, HMGB1, HSP70, C3a and C5a, but not IL-8, sCD86 or monocyte
chemoattractant protein-1, were significantly increased in the BDD group.
Significant differences were observed in flow cytometry analysis of TLR2 and TLR4
between the two groups. In summary, common methylprednisolone therapy in BDDs did
not adequately reduce systemic inflammation, which could be due to inadequate
doses or inefficient impact on other inflammatory-inducing pathways, for example
oxidative stress or production of damage-associated molecules.
PMID- 28504609
TI - Age and sex differences in serum adiponectin and its association with lipoprotein
fractions.
AB - Objective The correlation of adiponectin with cholesterol concentration of
fractionated lipoproteins has not been well investigated. Methods This study
included 174 subjects (79 men and 95 women) without diabetes. The medical record
data were investigated retrospectively. The study subjects with adiponectin <8.3,
> 8.3 but less 13.9, and >= 13.9 were classified into tertile groups: Groups A (
n = 59), B ( n = 58) and C ( n = 57), respectively. Results In women, age and HDL
C were higher in Group C than in Groups A and B, but BMI, TG, IDL-C and VLDL-C
were lower in Group C than in Groups A and B. In men, BMI was lower in Group C
than in Groups A and B, and HDL-C was higher in Group C than in Groups A and B.
In multiple stepwise regression analysis, BMI and HDL-C were significantly
correlated with adiponectin in whole, male and female subjects, but TG-rich
lipoprotein cholesterol concentrations were not independently correlated.
Conclusions HDL-C and BMI were independently correlated with adiponectin in non
diabetic men and women. These results suggest that high adiponectin may play a
role in the increased HDL-C concentrations, implicated in the reduction of
cardiovascular disease risk, in non-diabetic subjects.
PMID- 28504610
TI - Mind the gap: shortcomings of the osmotic gap and a possible solution.
AB - Background Measured (MO) and calculated osmotic concentrations (CO) and the
osmotic gap (OG) are commonly used in the investigation of electrolyte and volume
disturbances as well as in cases of suspected volatile ingestion. Methods We
compared 38 published formulae for CO with MO on a large data-set ( n = 9466) and
adjusted the CO with the result of a Passing-Bablok regression procedure.
Validation of this adjustment was performed with a separate data-set ( n = 2082).
Results All but one of the CO formulae underestimate MO due to a proportional
bias (slope 0.67 to 0.95) and the OG limits were therefore not applicable
throughout the observed range. Using Passing-Bablok regression to adjust the CO:
CO#3 = (2 * Na+urea+glucose-14.54)/0.93. After adjustment, the mean OG was 0.3
mmol/L with a SD of 5.1 mmol/L across the measurement interval. The distribution
of the OG could be fully explained by the analytical imprecision of the measured
components. Conclusions Simple adjustment of the CO for the proportional
underestimation of MO allows OG reference limits of approximately -10 to +10
mmol/L to be used, even in the upper ranges of CO in patients with suspected
volatile ingestion.
PMID- 28504611
TI - Evolocumab and clinical outcomes in patients with cardiovascular disease.
PMID- 28504612
TI - Changes in the albumin glycation site, plasma pentosidine and esRAGE
concentrations before and after intensive diabetic treatment in patients with
abnormally high glycated albumin levels.
AB - Background We have reported that the blood glucose normalization treatment
reduced the albumin glycation sites and the intensity of albumin AGE fluorescence
in patients with abnormally high glycated albumin levels. To clarify the
relationship between glycaemic control status and levels of glycated proteins and
related markers, we studied the change of the markers of the DM patients with and
without fatty liver, liver cirrhosis and dialysis before and after the intensive
diabetic treatment. Methods Eight diabetic patients with abnormally high glycated
albumin levels (no complications: 2, fatty liver: 3, liver cirrhosis: 2,
dialysis: 1) were recruited. In the hypoglycaemic treatment for these patients,
the HbA1c, glycated albumin, albumin AGE fluorescence, pentosidine, endogenous
secretory receptors for AGE (esRAGE) and glycation sites of albumin were
determined. Results Glycated albumin and HbA1c levels dropped after the
treatment. Albumin glycation sites decreased in almost the same pattern,
irrespective of the type of complications. The fluorescence intensity and
pentosidine concentrations decreased significantly. However, post-treatment
pentosidine concentrations were higher than the reference interval in all cases.
Average esRAGE concentrations did not change and were lower than the reference
interval. Conclusions Hypoglycaemic treatment reduced the glycated albumin
levels, glycation sites of albumin and AGE concentrations but not esRAGE
concentrations in diabetic patients with or without fatty liver, liver cirrhosis,
and dialysis. Checking and maintaining low glycated albumin levels would prevent
the formation of AGE and may be useful to prevent the onset or progression of
diabetes complications.
PMID- 28504614
TI - Quantifying the Effects of Water Temperature, Soap Volume, Lather Time, and
Antimicrobial Soap as Variables in the Removal of Escherichia coli ATCC 11229
from Hands.
AB - The literature on hand washing, while extensive, often contains conflicting data,
and key variables are only superficially studied or not studied at all. Some hand
washing recommendations are made without scientific support, and agreement
between recommendations is limited. The influence of key variables such as soap
volume, lather time, water temperature, and product formulation on hand washing
efficacy was investigated in the present study. Baseline conditions were 1 mL of
a bland (nonantimicrobial) soap, a 5-s lather time, and 38 degrees C (100 degrees
F) water temperature. A nonpathogenic strain of Escherichia coli (ATCC 11229) was
the challenge microorganism. Twenty volunteers (10 men and 10 women) participated
in the study, and each test condition had 20 replicates. An antimicrobial soap
formulation (1% chloroxylenol) was not significantly more effective than the
bland soap for removing E. coli under a variety of test conditions. Overall, the
mean reduction was 1.94 log CFU (range, 1.83 to 2.10 log CFU) with the
antimicrobial soap and 2.22 log CFU (range, 1.91 to 2.54 log CFU) with the bland
soap. Overall, lather time significantly influenced efficacy in one scenario, in
which a 0.5-log greater reduction was observed after 20 s with bland soap
compared with the baseline wash (P = 0.020). Water temperature as high as 38
degrees C (100 degrees F) and as low as 15 degrees C (60 degrees F) did not have
a significant effect on the reduction of bacteria during hand washing; however,
the energy usage differed between these temperatures. No significant differences
were observed in mean log reductions experienced by men and women (both 2.08 log
CFU; P = 0.988). A large part of the variability in the data was associated with
the behaviors of the volunteers. Understanding what behaviors and human factors
most influence hand washing may help researchers find techniques to optimize the
effectiveness of hand washing.
PMID- 28504613
TI - ChLpMab-23: Cancer-Specific Human-Mouse Chimeric Anti-Podoplanin Antibody
Exhibits Antitumor Activity via Antibody-Dependent Cellular Cytotoxicity.
AB - Podoplanin is expressed in many cancers, including oral cancers and brain tumors.
The interaction between podoplanin and its receptor C-type lectin-like receptor 2
(CLEC-2) has been reported to be involved in cancer metastasis and tumor
malignancy. We previously established many monoclonal antibodies (mAbs) against
human podoplanin using the cancer-specific mAb (CasMab) technology. LpMab-23
(IgG1, kappa), one of the mouse anti-podoplanin mAbs, was shown to be a CasMab.
However, we have not shown the usefulness of LpMab-23 for antibody therapy
against podoplanin-expressing cancers. In this study, we first determined the
minimum epitope of LpMab-23 and revealed that Gly54-Leu64 peptide, especially
Gly54, Thr55, Ser56, Glu57, Asp58, Arg59, Tyr60, and Leu64 of podoplanin, is a
critical epitope of LpMab-23. We further produced human-mouse chimeric LpMab-23
(chLpMab-23) and investigated whether chLpMab-23 exerts antibody-dependent
cellular cytotoxicity (ADCC) and antitumor activity. In flow cytometry, chLpMab
23 showed high sensitivity against a podoplanin-expressing glioblastoma cell
line, LN319, and an oral cancer cell line, HSC-2. chLpMab-23 also showed ADCC
activity against podoplanin-expressing CHO cells (CHO/podoplanin). In xenograft
models with HSC-2 and CHO/podoplanin, chLpMab-23 exerts antitumor activity using
human natural killer cells, indicating that chLpMab-23 could be useful for
antibody therapy against podoplanin-expressing cancers.
PMID- 28504615
TI - Perception Gaps on Food Additives among Various Groups in Korea: Food Experts,
Teachers, Nutrition Teachers, Nongovernmental Organization Members, and General
Consumers.
AB - The purpose of this study was to determine the perceptions and information needs
of food experts, teachers, nutrition teachers, members of nongovernmental
organizations, and general consumers concerning food additives. Questions in a
survey format included perceptions, information needs, and preferred
communication channels. The survey was conducted both off-line and on-line via e
mail and Google Drive in March 2015. The results indicated that most Korean
consumers are concerned about the safety of using food additives in processed
foods and do not recognize these additives as safe and useful materials as part
of a modern diet. We also identified perception gaps among different groups
regarding food additives. Nutrition teachers and members of nongovernmental
organizations in Korea appeared to have a biased perception of food additives,
which may cause general consumers to have a negative perception of food
additives. The group of food experts did not have this bias. Governmental
institutions must overcome the low confidence levels of various groups as an
information provider about food additives. Based on the findings in this study,
it will be possible to develop a strategy for risk communication about food
additives for each group.
PMID- 28504616
TI - Prevalence and Characterization of Campylobacter jejuni Isolated from Retail
Chicken in Tianjin, China.
AB - Campylobacter jejuni is an important foodborne pathogen worldwide; however, there
is a lack of information on the prevalence and antibiotic-resistant profile of C.
jejuni in the People's Republic of China. We determined the prevalence and
characteristics of C. jejuni on the retail level in Tianjin, one of the five
national central cities in China. A total of 227 samples of chicken wings, legs,
and breasts were collected from supermarkets and wet markets; 42 of these samples
were confirmed to be positive for Campylobacter contamination. The contamination
rates of C. jejuni and other Campylobacter species were 13.7% (31 of 227 samples)
and 5.7% (13 of 227 samples), respectively. A group of 31 C. jejuni isolates was
subjected to antimicrobial susceptibility testing. All (100%) the selected
isolates were resistant to ciprofloxacin and nalidixic acid; 77.4% were resistant
to tetracycline, 67.7% to doxycycline, 35.5% to gentamicin, 25.8% to clindamycin
and florfenicol, 19.4% to chloramphenicol, and 12.9% to erythromycin and
azithromycin. A remarkably high proportion (41.9%) of multidrug-resistant
isolates was identified. Multilocus sequence typing was conducted to study the
population structure of the C. jejuni strains and their relationship to human
isolates. The correlation between antimicrobial resistance traits and certain
sequence types (STs) or clonal complexes was determined as well. A great genetic
diversity of poultry isolates was identified, with 11 STs belonging to 6 clonal
complexes and 11 singleton STs. The novel STs accounted for 40.9% (n = 9) of the
22 STs. ST-21, ST-353, ST-354, ST-443, ST-607, and ST-828 complexes had been
previously identified from human isolates. This study revealed an extensive level
of antimicrobial resistance and genetic diversity in C. jejuni isolated from
chicken products in Tianjin, highlighting the necessity of performing enforced
interventions to reduce Campylobacter prevalence in China.
PMID- 28504619
TI - Standard Area Diagrams for Aiding Severity Estimation: Scientometrics,
Pathosystems, and Methodological Trends in the Last 25 Years.
AB - Standard area diagrams (SAD) have long been used as a tool to aid the estimation
of plant disease severity, an essential variable in phytopathometry. Formal
validation of SAD was not considered prior to the early 1990s, when considerable
effort began to be invested developing SAD and assessing their value for
improving accuracy of estimates of disease severity in many pathosystems. Peer
reviewed literature post-1990 was identified, selected, and cataloged in
bibliographic software for further scrutiny and extraction of scientometric,
pathosystem-related, and methodological-related data. In total, 105 studies (127
SAD) were found and authored by 327 researchers from 10 countries, mainly from
Brazil. The six most prolific authors published at least seven studies. The
scientific impact of a SAD article, based on annual citations after publication
year, was affected by disease significance, the journal's impact factor, and
methodological innovation. The reviewed SAD encompassed 48 crops and 103 unique
diseases across a range of plant organs. Severity was quantified largely by image
analysis software such as QUANT, APS-Assess, or a LI-COR leaf area meter. The
most typical SAD comprised five to eight black-and-white drawings of leaf
diagrams, with severity increasing nonlinearly. However, there was a trend toward
using true-color photographs or stylized representations in a range of color
combinations and more linear (equally spaced) increments of severity. A two-step
SAD validation approach was used in 78 of 105 studies for which linear regression
was the preferred method but a trend toward using Lin's correlation concordance
analysis and hypothesis tests to detect the effect of SAD on accuracy was
apparent. Reliability measures, when obtained, mainly considered variation among
rather than within raters. The implications of the findings and knowledge gaps
are discussed. A list of best practices for designing and implementing SAD and a
website called SADBank for hosting SAD research data are proposed.
PMID- 28504621
TI - [A stroke mimic: hemichorea associated with non-ketotic hyperglycaemia].
AB - An 85-year-old man with a history of diabetes was admitted with acute onset
hemichorea. Laboratory findings confirmed poorly controlled diabetes. A brain
computed tomography (CTC) revealed contralateral striatal hyperdensity. The
findings were compatible with hyperglycaemia-induced hemichorea, and antidiabetic
and symptomatic treatment was initiated. The symptoms remitted completely after
six days, and a follow-up CTC showed partial resolution of the striatal changes.
This case illustrates the importance of considering if hyperglycaemia is the
cause of hemichorea, as early diagnosis and treatment yield an excellent
prognosis.
PMID- 28504620
TI - Identification of a distinctive phenotype for endocarditis-associated clonal
complex 22 MRSA isolates with reduced vancomycin susceptibility.
AB - PURPOSE: We previously identified an association between CC22 meticillin
resistant Staphylococcus aureus (MRSA) bloodstream infection isolates with an
elevated vancomycin MIC (V-MIC) in the susceptible range (1.5-2 mg l-1) and
endocarditis. This study explores whether these isolates have a specific
phenotype consistent with the clinical findings. METHODOLOGY: CC22 and CC30 MRSA
isolates with high (1.5-2 mg l-1) and low (<=0.5 mg l-1) V-MICs were tested for
fibrinogen and fibronectin binding, virulence in a Galleria mellonella
caterpillar model, phenol soluble modulin production and accessory gene regulator
(agr) expression. RESULTS: CC22 high V-MIC, but not CC30 high V-MIC isolates,
showed sustained fibrinogen binding through a stationary growth phase and
increased PSM production, specifically PSMalpha1, compared with respective low V
MIC isolates. Expression was lower in both CC22 and CC30 high V-MIC isolates
compared with respective low V-MIC isolates, although there was no associated
reduction in virulence in the caterpillar model. CONCLUSIONS: The identification
of a distinct phenotype for CC22 high V-MIC isolates supports the hypothesis that
bacterial factors contribute to the mechanism underlying their association with
endocarditis. Further study of these isolates could shed light on the molecular
mechanism of endocarditis in humans.
PMID- 28504618
TI - Butyrate reduces high-fat diet-induced metabolic alterations, hepatic steatosis
and pancreatic beta cell and intestinal barrier dysfunctions in prediabetic mice.
AB - In this study, we investigated the effect of diet supplementation with sodium
butyrate (5% w/w), a short-chain fatty acid produced by the intestinal
microbiota, on metabolic parameters, body adiposity, hepatic and pancreatic lipid
accumulation, beta cell function/mass as well as on the structure and function of
the tight junction-mediated intestinal epithelial barrier in both normal and
obese/prediabetic C57 mice fed a regular (control) or high-fat diet for 60 days,
respectively. Butyrate treatment significantly inhibited all the high-fat-induced
metabolic dysfunctions evaluated, i.e. significantly reduced the weight gain and
body adiposity as well as the insulin resistant state, hyperglycemia and
hyperinsulinemia, without changing food intake. In addition, high-fat-fed mice
treated with this short-chain fatty acid displayed no compensatory hyperplasia of
pancreatic beta cells nor marked hepatic steatosis as seen in prediabetic mice
after high-fat diet only. Isolated pancreatic islets from high-fat-fed mice
treated with butyrate showed improvement of the insulin secretion, which was
associated with a significant decrease in lipid accumulation within the pancreas.
Butyrate enhanced the intestinal epithelial barrier, as revealed by the FITC
Dextran permeability assay, which was accompanied by a significant increase in
the junctional content of the tight junction-associated claudin-1 in intestinal
epithelia of jejunum, ileum, and colon of both control and high-fat mice. In
conclusion, our results showed that diet supplementation with butyrate inhibits
the deleterious effects of high-fat diet intake on metabolic parameters and
structure/function of several tissues/organs associated with type 2 diabetes
mellitus in a mouse model, suggesting a potential use of this short-chain fatty
acid in the treatment of this endocrine-metabolic disorder. Impact statement
Butyrate is a short-chain fatty acid produced by the intestinal microbiota
through the fermentation of non-absorbable carbohydrates and proteins (e.g.
fibers). Sodium butyrate incorporated into the diet displayed a protective action
on metabolic, hepatic, pancreatic and intestinal alterations induced by high-fat
diet in mice, resulting in significant inhibition of the development of a
prediabetic state. Thus, our data suggest that butyrate may have a potential
therapeutic use in the treatment of type 2 diabetes and related disorders.
PMID- 28504622
TI - [Severe cervical kyphosis causing sudden inspiratory stridor].
AB - An 85-year-old woman was brought to an accident and emergency department with
breathing difficulties accompanied by inspiratory stridor. She was being treated
for hypertension and severe osteoporosis which had caused thoracal and cervical
fractures of the columna. Intubation was initiated as she desaturated and
deteriorated despite maximum oxygen therapy. The intubation revealed a subglottic
stenosis as a consequence of a recent osteoporotic fracture in the cervical
columna. This represents a rare cause of respiratory failure as all other
cardial, pulmonary and allergic aetiologies had been eliminated.
PMID- 28504617
TI - Opportunities and challenges in the wider adoption of liver and interconnected
microphysiological systems.
AB - Liver disease represents a growing global health burden. The development of in
vitro liver models which allow the study of disease and the prediction of
metabolism and drug-induced liver injury in humans remains a challenge. The
maintenance of functional primary hepatocytes cultures, the parenchymal cell of
the liver, has historically been difficult with dedifferentiation and the
consequent loss of hepatic function limiting utility. The desire for longer term
functional liver cultures sparked the development of numerous systems, including
collagen sandwiches, spheroids, micropatterned co-cultures and liver
microphysiological systems. This review will focus on liver microphysiological
systems, often referred to as liver-on-a-chip, and broaden to include platforms
with interconnected microphysiological systems or multi-organ-chips. The
interconnection of microphysiological systems presents the opportunity to explore
system level effects, investigate organ cross talk, and address questions which
were previously the preserve of animal experimentation. As a field,
microphysiological systems have reached a level of maturity suitable for
commercialization and consequent evaluation by a wider community of users, in
academia and the pharmaceutical industry. Here scientific, operational, and
organizational considerations relevant to the wider adoption of
microphysiological systems will be discussed. Applications in which
microphysiological systems might offer unique scientific insights or enable
studies currently feasible only with animal models are described, and challenges
which might be addressed to enable wider adoption of the technologies are
highlighted. A path forward which envisions the development of microphysiological
systems in partnerships between academia, vendors and industry, is proposed.
Impact statement Microphysiological systems are in vitro models of human tissues
and organs. These systems have advanced rapidly in recent years and are now being
commercialized. To achieve wide adoption in the biological and pharmaceutical
research communities, microphysiological systems must provide unique insights
which translate to humans. This will be achieved by identifying key applications
and making microphysiological systems intuitive to use.
PMID- 28504623
TI - [Family psychoeducation for affective disorders].
AB - The aim of this article was to examine the evidence of family psychoeducation
(FPE) for affective disorders. Evidence indicates that FPE can be an effective
supplement to the standard treatment of patients with affective disorders. FPE
can effectively reduce the patients' risk of relapse and reduce the burden
experienced by the relatives. However, current studies are very heterogeneous and
therefore difficult to compare. Up to this point the evidence regarding the
effect of FPE on unipolar depression is still very sparse and further research is
needed.
PMID- 28504624
TI - [Damage control surgery in patients with abdominal sepsis].
AB - Damage control surgery (DCS) and resuscitation has improved the survival of
trauma patients with decompensated physiology. In recent years, the principles of
DCS have been used in the treatment of patients with abdominal sepsis, despite
the fact that only a minimum of evidence exists. The aim is to optimize the
physiology prior to definitive surgery. This implies a primary decontaminating
surgical procedure with temporary abdominal closure without restoration of the
intestinal continuity and avoidance of stoma formation in order to reduce time in
the operating theatre.
PMID- 28504625
TI - ?
PMID- 28504626
TI - [Danish malaria research from the frail beginning to internationally acknowledged
research].
AB - Malaria - and particularly the disease caused by Plasmodium falciparum - remains
a direct as well as indirect cause of poverty and immense human suffering.
Research is imperative to alleviate this situation and to control and eventually
eradicate the disease. Since the mid-1970s, Danish scientists have contributed
increasingly to this effort by publishing more than 700 scientific papers and by
training about 60 highly skilled malaria researchers. The efforts which continue
to be thoroughly dependent on extensive external funding and public goodwill are
briefly reviewed in this article.
PMID- 28504627
TI - [High-isolation preparedness for very contagious and potential severely ill
patients].
AB - Ten and seven years ago respectively, the two high-isolation units in Denmark
became prepared to receive highly contagious and potential severely ill patients.
The units are located in the departments of infectious diseases in Hvidovre
Hospital and Aarhus University Hospital. Both departments had little experience
until the Ebola outbreak in West Africa, 2013-2015. Altogether, 15 possible Ebola
patients were examined in the two departments, but the diagnosis was ruled out
for all of them. Besides, a few possible candidates for Middle East respiratory
syndrome patients were examined. Always being prepared in a busy clinical
everyday environment is a challenge, and it takes regular training and exercises
involving all personnel.
PMID- 28504628
TI - [The current global tuberculosis state].
AB - Despite an increase in the total number of tuberculosis (TB) patients globally,
positive trends in reduction of prevalence and mortality are observed. However,
high numbers of drug-resistant cases are threatening this trend. Multidrug
resistant and extensively resistant cases constitute an increasing challenge in
many parts of the world also within the European region - especially in former
Sovjet Republic nations. Point-of-care test systems potentially replacing
microscopy and urine antigen detection systems are currently launched in many TB
high endemic countries improving TB detection rates. However, the effect on key
indicators like mortality is still waiting to break through.
PMID- 28504629
TI - [Acute malnutrition in children].
AB - The prevalence of malnutrition has declined significantly over the last 30 years.
Despite this, malnutrition remains a major cause of illness and death among
children worldwide, particularly in low- and medium-income countries. Marasmus
and kwashiorkor are the most life-threatening forms of malnutrition. Treatment
protocols enable effective treatment, but only a minority of malnourished
children have access to treatment. Furthermore, treating children with
complicated malnutrition requiring hospitalization remains a clinical challenge.
PMID- 28504630
TI - [Global differences in causes and diagnostics of cardio-metabolic diseases].
AB - Cardio-metabolic diseases (CMDs) such as obesity, type 2 diabetes (T2D) and
hypertension are now highly prevalent throughout low- and middle-income
countries, even though half of the T2D cases cannot be explained by obesity. Non
obese T2D individuals may have been exposed to foetal programming and/or be
genetically susceptible to abdominal obesity. There is evidence for ethnic
specific risks for cardiometabolic disease. This calls for expanding research
collaboration with so-called South partners in order to qualify decision making
on diagnosis and prevention of CMDs at global level.
PMID- 28504631
TI - [Climate change, floods and health intervention].
AB - Climate change and variability are considered some of the biggest threats to
human health in the 21st century. Extreme weather events such as floods and
storms are examples of natural hazards resulting in highest number of disasters
and with considerable mortality and morbidity among vulnerable communities. A
coordinated, well-planned management of health interventions must be taken for
timely action in the response, recovery, prevention and preparedness phases of
disasters. Roles and responsibilities of international as well as national
organizations and authorities are discussed.
PMID- 28504632
TI - [Medical tourism and its implications for patients and hospital services
throughout the world].
AB - This article provides a snapshot of global medical tourism and its positive and
negative implications for healthcare around the world presented through selected
examples. Medical tourism is an old phenomenon which has seen a rapid increase
due to global technological advances thus enabling people to receive treatment
anywhere in the world, often combined with a tropical vacation. Treatments are of
a non-acute, voluntary nature and are driven largely by high prices and long
waiting lists at the home countries and low prices and high service quality at
the destination country.
PMID- 28504633
TI - [Tick-borne infections in Denmark].
AB - The castor bean tick, Ixodes ricinus, is common in woodlands in most of Denmark.
Besides Borrelia burgdorferi, it can harbour a number of pathogenic
microorganisms such as tick-borne encephalitis virus, Anaplasma phagocytophilum,
Rickettsia helvetica, Francisella tularensis, Candidatus Neoehrlichia mikurensis,
Bartonella spp., Borrelia miyamotoi and Babesia spp. These tick-borne infections
should be a differential diagnostic consideration during the tick season in
Denmark. We review the distribution, clinical manifestations, diagnosis and
treatment of these microorganisms.
PMID- 28504634
TI - [A burned-out seminoma lymph node metastasis to the neck of a patient treated for
colon cancer].
AB - The incidence of metastases to the neck in testicular cancer is 4-15%, and in 5%
of these cases the metastasis is the only symptom. We present a 57-year-old
asymptomatic male, who had previously been treated for colon cancer. A routine
PET-CT showed enlarged lymph nodes in the retroperitoneum and at the neck. A core
needle biopsy from the lymph node at the neck contained malignant cells, but not
from colon cancer. The lymph node was extirpated, and pathological analysis
proved it to be a metastasis from a testicular seminoma. A burned-out seminoma
was subsequently found in the patient's right testicle.
PMID- 28504635
TI - [Favism after ingestion of fava beans in a three-year-old child with glucose-6
phosphate dehydrogenase deficiency].
AB - A three-year-old Syrian boy was hospitalized with symptoms of acute haemolytic
anaemia after ingestion of fava beans. He was stabilized by blood transfusion,
and genetic examination revealed glucose-6-phosphate dehydrogenase (G6PD)
deficiency. Oxidative stress, e.g. ingestion of fava beans, can induce acute
haemolytic anaemia in affected individuals. Approximately 400 million people
worldwide suffer from G6PD deficiency. The prevalence is high in African,
Mediterranean and Middle East countries. Due to increased immigration, we might
expect the condition to occur more often in Danish healthcare.
PMID- 28504636
TI - [Eggs do not increase the risk of cardiovascular disease and can be safely
consumed].
AB - Eggs are nutrient dense, rich in essential amino- and fatty acids, and the most
cholesterol containing food. Based on observational studies the consumption of
eggs has since the 1970's been claimed to increase the risk of cardiovascular
disease (CVD). Intervention studies on intake of eggs and plasma cholesterol do
however not support causality. The higher incidence of CVD in egg eaters is more
likely to be caused by the clustering of other CVD risk factors. Up to seven eggs
per week can safely be consumed but in patients with CVD or diabetes only with
special emphasis on a prudent diet and proper medical treatment.
PMID- 28504637
TI - [Evidence of the effect of psychodynamic psychotherapy].
AB - Evidence of the effect of psychodynamic psychotherapy (PDT) has been called into
question. Thus, an updated review of the effect of short-term and long-term PDT
(STPP and LTPP) for anxiety, depression and personality disorders seems
necessary. A systematic search of randomized controlled studies of PDT published
from January 2000 to May 2016 was conducted, and we found 57 single studies and
13 meta-analyses fulfilling the criteria for inclusion. The studies show that PDT
has therapeutic efficacy and effectiveness matching other forms of psychotherapy.
LTPP shows better effect than STPP in the treatment of complex psychiatric
disorders and long-term depression.
PMID- 28504638
TI - Catecholaminergic challenge uncovers distinct Pavlovian and instrumental
mechanisms of motivated (in)action.
AB - Catecholamines modulate the impact of motivational cues on action. Such
motivational biases have been proposed to reflect cue-based, 'Pavlovian' effects.
Here, we assess whether motivational biases may also arise from asymmetrical
instrumental learning of active and passive responses following reward and
punishment outcomes. We present a novel paradigm, allowing us to disentangle the
impact of reward and punishment on instrumental learning from Pavlovian response
biasing. Computational analyses showed that motivational biases reflect both
Pavlovian and instrumental effects: reward and punishment cues promoted
generalized (in)action in a Pavlovian manner, whereas outcomes enhanced
instrumental (un)learning of chosen actions. These cue- and outcome-based biases
were altered independently by the catecholamine enhancer melthylphenidate.
Methylphenidate's effect varied across individuals with a putative proxy of
baseline dopamine synthesis capacity, working memory span. Our study uncovers two
distinct mechanisms by which motivation impacts behaviour, and helps refine
current models of catecholaminergic modulation of motivated action.
PMID- 28504639
TI - Structural basis of cooperativity in kinesin revealed by 3D reconstruction of a
two-head-bound state on microtubules.
AB - The detailed basis of walking by dimeric molecules of kinesin along microtubules
has remained unclear, partly because available structural methods have been
unable to capture microtubule-bound intermediates of this process. Utilizing
novel electron cryomicroscopy methods, we solved structures of microtubule
attached, dimeric kinesin bound to an ATP analog. We find that under these
conditions, the kinesin dimer can attach to the microtubule with either one or
two motor domains, and we present sub-nanometer resolution reconstructions of
both states. The former structure reveals a novel kinesin conformation that
revises the current understanding of how ATP binding is coupled to forward
stepping of the motor. The latter structure indicates how tension between the two
motor domains keeps their cycles out of phase in order to stimulate directional
motility. The methods presented here pave the way for future structural studies
of a variety of challenging macromolecules that bind to microtubules and other
filaments.
PMID- 28504640
TI - The Sec61 translocon limits IRE1alpha signaling during the unfolded protein
response.
AB - IRE1alpha is an endoplasmic reticulum (ER) localized endonuclease activated by
misfolded proteins in the ER. Previously, we demonstrated that IRE1alpha forms a
complex with the Sec61 translocon, to which its substrate XBP1u mRNA is recruited
for cleavage during ER stress (Plumb et al., 2015). Here, we probe IRE1alpha
complexes in cells with blue native PAGE immunoblotting. We find that IRE1alpha
forms a hetero-oligomeric complex with the Sec61 translocon that is activated
upon ER stress with little change in the complex. In addition, IRE1alpha
oligomerization, activation, and inactivation during ER stress are regulated by
Sec61. Loss of the IRE1alpha-Sec61 translocon interaction as well as severe ER
stress conditions causes IRE1alpha to form higher-order oligomers that exhibit
continuous activation and extended cleavage of XBP1u mRNA. Thus, we propose that
the Sec61-IRE1alpha complex defines the extent of IRE1alpha activity and may
determine cell fate decisions during ER stress conditions.
PMID- 28504642
TI - Ion recombination correction factor in scanned light-ion beams for absolute dose
measurement using plane-parallel ionisation chambers.
AB - Based on international reference dosimetry protocols for light-ion beams, a
correction factor (k s) has to be applied to the response of a plane-parallel
ionisation chamber, to account for recombination of negative and positive charges
in its air cavity before these charges can be collected on the electrodes. In
this work, k s for IBA PPC40 Roos-type chambers is investigated in four scanned
light-ion beams (proton, helium, carbon and oxygen). To take into account the
high dose-rates used with scanned beams and LET-values, experimental results are
compared to a model combining two theories. One theory, developed by Jaffe,
describes the variation of k s with the ionization density within the ion track
(initial recombination) and the other theory, developed by Boag, describes the
variation of k s with the dose rate (volume recombination). Excellent agreement
is found between experimental and theoretical k s-values. All results confirm
that k s cannot be neglected. The solution to minimise k s is to use the
ionisation chamber at high voltage. However, one must be aware that charge
multiplication may complicate the interpretation of the measurement. For the
chamber tested, it was found that a voltage of 300 V can be used without further
complication. As the initial recombination has a logarithmic variation as a
function of 1/V, the two-voltage method is not applicable to these scanned beams.
PMID- 28504643
TI - Exploiting neurovascular coupling: a Bayesian sequential Monte Carlo approach
applied to simulated EEG fNIRS data.
AB - OBJECTIVE: Electrical and hemodynamic brain activity are linked through the
neurovascular coupling process and they can be simultaneously measured through
integration of electroencephalography (EEG) and functional near-infrared
spectroscopy (fNIRS). Thanks to the lack of electro-optical interference, the two
procedures can be easily combined and, whereas EEG provides electrophysiological
information, fNIRS can provide measurements of two hemodynamic variables, such as
oxygenated and deoxygenated hemoglobin. A Bayesian sequential Monte Carlo
approach (particle filter, PF) was applied to simulated recordings of electrical
and neurovascular mediated hemodynamic activity, and the advantages of a unified
framework were shown. APPROACH: Multiple neural activities and hemodynamic
responses were simulated in the primary motor cortex of a subject brain. EEG and
fNIRS recordings were obtained by means of forward models of volume conduction
and light propagation through the head. A state space model of combined EEG and
fNIRS data was built and its dynamic evolution was estimated through a Bayesian
sequential Monte Carlo approach (PF). MAIN RESULTS: We showed the feasibility of
the procedure and the improvements in both electrical and hemodynamic brain
activity reconstruction when using the PF on combined EEG and fNIRS measurements.
SIGNIFICANCE: The investigated procedure allows one to combine the information
provided by the two methodologies, and, by taking advantage of a physical model
of the coupling between electrical and hemodynamic response, to obtain a better
estimate of brain activity evolution. Despite the high computational demand,
application of such an approach to in vivo recordings could fully exploit the
advantages of this combined brain imaging technology.
PMID- 28504644
TI - Direct reconstruction of parametric images for brain PET with event-by-event
motion correction: evaluation in two tracers across count levels.
AB - Parametric images for dynamic positron emission tomography (PET) are typically
generated by an indirect method, i.e. reconstructing a time series of emission
images, then fitting a kinetic model to each voxel time activity curve.
Alternatively, 'direct reconstruction', incorporates the kinetic model into the
reconstruction algorithm itself, directly producing parametric images from
projection data. Direct reconstruction has been shown to achieve parametric
images with lower standard error than the indirect method. Here, we present
direct reconstruction for brain PET using event-by-event motion correction of
list-mode data, applied to two tracers. Event-by-event motion correction was
implemented for direct reconstruction in the Parametric Motion-compensation OSEM
List-mode Algorithm for Resolution-recovery reconstruction. The direct
implementation was tested on simulated and human datasets with tracers [11C]AFM
(serotonin transporter) and [11C]UCB-J (synaptic density), which follow the 1
tissue compartment model. Rigid head motion was tracked with the Vicra system.
Parametric images of K 1 and distribution volume (V T = K 1/k 2) were compared
to those generated by the indirect method by regional coefficient of variation
(CoV). Performance across count levels was assessed using sub-sampled datasets.
For simulated and real datasets at high counts, the two methods estimated K 1 and
V T with comparable accuracy. At lower count levels, the direct method was
substantially more robust to outliers than the indirect method. Compared to the
indirect method, direct reconstruction reduced regional K 1 CoV by 35-48%
(simulated dataset), 39-43% ([11C]AFM dataset) and 30-36% ([11C]UCB-J dataset)
across count levels (averaged over regions at matched iteration); V T CoV was
reduced by 51-58%, 54-60% and 30-46%, respectively. Motion correction played an
important role in the dataset with larger motion: correction increased regional V
T by 51% on average in the [11C]UCB-J dataset. Direct reconstruction of dynamic
brain PET with event-by-event motion correction is achievable and dramatically
more robust to noise in V T images than the indirect method.
PMID- 28504641
TI - Helical jackknives control the gates of the double-pore K+ uptake system KtrAB.
AB - Ion channel gating is essential for cellular homeostasis and is tightly
controlled. In some eukaryotic and most bacterial ligand-gated K+ channels, RCK
domains regulate ion fluxes. Until now, a single regulatory mechanism has been
proposed for all RCK-regulated channels, involving signal transduction from the
RCK domain to the gating area. Here, we present an inactive ADP-bound structure
of KtrAB from Vibrio alginolyticus, determined by cryo-electron microscopy,
which, combined with EPR spectroscopy and molecular dynamics simulations,
uncovers a novel regulatory mechanism for ligand-induced action at a distance.
Exchange of activating ATP to inactivating ADP triggers short helical segments in
the K+-translocating KtrB dimer to organize into two long helices that penetrate
deeply into the regulatory RCK domains, thus connecting nucleotide-binding sites
and ion gates. As KtrAB and its homolog TrkAH have been implicated as bacterial
pathogenicity factors, the discovery of this functionally relevant inactive
conformation may advance structure-guided drug development.
PMID- 28504645
TI - Molecular isoforms of high-mobility group box 1 are mechanistic biomarkers for
epilepsy.
AB - Approximately 30% of epilepsy patients do not respond to antiepileptic drugs,
representing an unmet medical need. There is evidence that neuroinflammation
plays a pathogenic role in drug-resistant epilepsy. The high-mobility group box 1
(HMGB1)/TLR4 axis is a key initiator of neuroinflammation following epileptogenic
injuries, and its activation contributes to seizure generation in animal models.
However, further work is required to understand the role of HMGB1 and its
isoforms in epileptogenesis and drug resistance. Using a combination of animal
models and sera from clinically well-characterized patients, we have demonstrated
that there are dynamic changes in HMGB1 isoforms in the brain and blood of
animals undergoing epileptogenesis. The pathologic disulfide HMGB1 isoform
progressively increased in blood before epilepsy onset and prospectively
identified animals that developed the disease. Consistent with animal data, we
observed early expression of disulfide HMGB1 in patients with newly diagnosed
epilepsy, and its persistence was associated with subsequent seizures. In
contrast with patients with well-controlled epilepsy, patients with chronic, drug
refractory epilepsy persistently expressed the acetylated, disulfide HMGB1
isoforms. Moreover, treatment of animals with antiinflammatory drugs during
epileptogenesis prevented both disease progression and blood increase in HMGB1
isoforms. Our data suggest that HMGB1 isoforms are mechanistic biomarkers for
epileptogenesis and drug-resistant epilepsy in humans, necessitating evaluation
in larger-scale prospective studies.
PMID- 28504646
TI - The RNA-binding protein tristetraprolin schedules apoptosis of pathogen-engaged
neutrophils during bacterial infection.
AB - Protective responses against pathogens require a rapid mobilization of resting
neutrophils and the timely removal of activated ones. Neutrophils are
exceptionally short-lived leukocytes, yet it remains unclear whether the lifespan
of pathogen-engaged neutrophils is regulated differently from that in the
circulating steady-state pool. Here, we have found that under homeostatic
conditions, the mRNA-destabilizing protein tristetraprolin (TTP) regulates
apoptosis and the numbers of activated infiltrating murine neutrophils but not
neutrophil cellularity. Activated TTP-deficient neutrophils exhibited decreased
apoptosis and enhanced accumulation at the infection site. In the context of
myeloid-specific deletion of Ttp, the potentiation of neutrophil deployment
protected mice against lethal soft tissue infection with Streptococcus pyogenes
and prevented bacterial dissemination. Neutrophil transcriptome analysis revealed
that decreased apoptosis of TTP-deficient neutrophils was specifically associated
with elevated expression of myeloid cell leukemia 1 (Mcl1) but not other
antiapoptotic B cell leukemia/lymphoma 2 (Bcl2) family members. Higher Mcl1
expression resulted from stabilization of Mcl1 mRNA in the absence of TTP. The
low apoptosis rate of infiltrating TTP-deficient neutrophils was comparable to
that of transgenic Mcl1-overexpressing neutrophils. Our study demonstrates that
posttranscriptional gene regulation by TTP schedules the termination of the
antimicrobial engagement of neutrophils. The balancing role of TTP comes at the
cost of an increased risk of bacterial infections.
PMID- 28504648
TI - The SO(H)L(H) "O" drivers of oocyte growth and survival but not meiosis I.
AB - The spermatogenesis/oogenesis helix-loop-helix (SOHLH) proteins SOHLH1 and SOHLH2
play important roles in male and female reproduction. Although previous studies
indicate that these transcriptional regulators are expressed in and have in vivo
roles in postnatal ovaries, their expression and function in the embryonic ovary
remain largely unknown. Because oocyte differentiation is tightly coupled with
the onset of meiosis, it is of significant interest to determine how early oocyte
transcription factors regulate these two processes. In this issue of the JCI,
Shin and colleagues report that SOHLH1 and SOHLH2 demonstrate distinct expression
patterns in the embryonic ovary and interact with each other and other oocyte
specific transcription factors to regulate oocyte differentiation. Interestingly,
even though there is a rapid loss of oocytes postnatally in ovaries with combined
loss of Sohlh1 and Sohlh2, meiosis is not affected and proceeds normally.
PMID- 28504647
TI - Identification of a nucleoside analog active against adenosine kinase-expressing
plasma cell malignancies.
AB - Primary effusion lymphoma (PEL) is a largely incurable malignancy of B cell
origin with plasmacytic differentiation. Here, we report the identification of a
highly effective inhibitor of PEL. This compound, 6-ethylthioinosine (6-ETI), is
a nucleoside analog with toxicity to PEL in vitro and in vivo, but not to other
lymphoma cell lines tested. We developed and performed resistome analysis, an
unbiased approach based on RNA sequencing of resistant subclones, to discover the
molecular mechanisms of sensitivity. We found different adenosine kinase
inactivating (ADK-inactivating) alterations in all resistant clones and
determined that ADK is required to phosphorylate and activate 6-ETI. Further, we
observed that 6-ETI induces ATP depletion and cell death accompanied by S phase
arrest and DNA damage only in ADK-expressing cells. Immunohistochemistry for ADK
served as a biomarker approach to identify 6-ETI-sensitive tumors, which we
documented for other lymphoid malignancies with plasmacytic features. Notably,
multiple myeloma (MM) expresses high levels of ADK, and 6-ETI was toxic to MM
cell lines and primary specimens and had a robust antitumor effect in a
disseminated MM mouse model. Several nucleoside analogs are effective in treating
leukemias and T cell lymphomas, and 6-ETI may fill this niche for the treatment
of PEL, plasmablastic lymphoma, MM, and other ADK-expressing cancers.
PMID- 28504649
TI - Activation of tumor suppressor protein PP2A inhibits KRAS-driven tumor growth.
AB - Targeted cancer therapies, which act on specific cancer-associated molecular
targets, are predominantly inhibitors of oncogenic kinases. While these drugs
have achieved some clinical success, the inactivation of kinase signaling via
stimulation of endogenous phosphatases has received minimal attention as an
alternative targeted approach. Here, we have demonstrated that activation of the
tumor suppressor protein phosphatase 2A (PP2A), a negative regulator of multiple
oncogenic signaling proteins, is a promising therapeutic approach for the
treatment of cancers. Our group previously developed a series of orally
bioavailable small molecule activators of PP2A, termed SMAPs. We now report that
SMAP treatment inhibited the growth of KRAS-mutant lung cancers in mouse
xenografts and transgenic models. Mechanistically, we found that SMAPs act by
binding to the PP2A Aalpha scaffold subunit to drive conformational changes in
PP2A. These results show that PP2A can be activated in cancer cells to inhibit
proliferation. Our strategy of reactivating endogenous PP2A may be applicable to
the treatment of other diseases and represents an advancement toward the
development of small molecule activators of tumor suppressor proteins.
PMID- 28504652
TI - A SMAP in the face for cancer.
AB - Observed deficits in protein phosphatase 2A (PP2A) function in a variety of human
cancers have stimulated drug discovery efforts aimed at restoring PP2A function
to inhibit tumor growth. Work published by Sangodkar et al. in this issue of the
JCI describes the characterization of orally available small molecule activators
of PP2A (SMAPs). These SMAPs attenuated mitogenic signaling and triggered
apoptosis in KRAS-mutant lung cancer cells and inhibited tumor growth in murine
models. Tumors with mutations in the SMAP-binding site of the PP2A A subunit
displayed resistance to SMAPs. Future studies that identify the PP2A-regulated
events targeted by SMAPs should guide critical decisions about which cancers
might be best treated with these molecules. This study provides encouraging
evidence in favor of SMAPs as potential anticancer drugs.
PMID- 28504650
TI - Neutrophil-derived S100 calcium-binding proteins A8/A9 promote reticulated
thrombocytosis and atherogenesis in diabetes.
AB - Platelets play a critical role in atherogenesis and thrombosis-mediated
myocardial ischemia, processes that are accelerated in diabetes. Whether
hyperglycemia promotes platelet production and whether enhanced platelet
production contributes to enhanced atherothrombosis remains unknown. Here we
found that in response to hyperglycemia, neutrophil-derived S100 calcium-binding
proteins A8/A9 (S100A8/A9) interact with the receptor for advanced glycation end
products (RAGE) on hepatic Kupffer cells, resulting in increased production of IL
6, a pleiotropic cytokine that is implicated in inflammatory thrombocytosis. IL-6
acts on hepatocytes to enhance the production of thrombopoietin, which in turn
interacts with its cognate receptor c-MPL on megakaryocytes and bone marrow
progenitor cells to promote their expansion and proliferation, resulting in
reticulated thrombocytosis. Lowering blood glucose using a sodium-glucose
cotransporter 2 inhibitor (dapagliflozin), depleting neutrophils or Kupffer
cells, or inhibiting S100A8/A9 binding to RAGE (using paquinimod), all reduced
diabetes-induced thrombocytosis. Inhibiting S100A8/A9 also decreased
atherogenesis in diabetic mice. Finally, we found that patients with type 2
diabetes have reticulated thrombocytosis that correlates with glycated hemoglobin
as well as increased plasma S100A8/A9 levels. These studies provide insights into
the mechanisms that regulate platelet production and may aid in the development
of strategies to improve on current antiplatelet therapies and to reduce
cardiovascular disease risk in diabetes.
PMID- 28504651
TI - Aging and the immune response to organ transplantation.
AB - An increasing number of older people receive organ transplants for various end
stage conditions. Although organ transplantation is an effective therapy for
older patients (i.e., older than 65 years of age), such as in end-stage renal
disease, this therapy has not been optimized for older patients because of our
lack of understanding of the effect of aging and the immune response to organ
transplantation. Here, we provide an overview of the impact of aging on both the
allograft and the recipient and its effect on the immune response to organ
transplantation. We describe what has been determined to date, discuss existing
gaps in our knowledge, and make suggestions on necessary future studies to
optimize organ transplantation for older people.
PMID- 28504653
TI - Metabolic shifts in residual breast cancer drive tumor recurrence.
AB - Tumor recurrence is the leading cause of breast cancer-related death. Recurrences
are largely driven by cancer cells that survive therapeutic intervention. This
poorly understood population is referred to as minimal residual disease. Here,
using mouse models that faithfully recapitulate human disease together with
organoid cultures, we have demonstrated that residual cells acquire a
transcriptionally distinct state from normal epithelium and primary tumors. Gene
expression changes and functional characterization revealed altered lipid
metabolism and elevated ROS as hallmarks of the cells that survive tumor
regression. These residual cells exhibited increased oxidative DNA damage,
potentiating the acquisition of somatic mutations during hormonal-induced
expansion of the mammary cell population. Inhibition of either cellular fatty
acid synthesis or fatty acid transport into mitochondria reduced cellular ROS
levels and DNA damage, linking these features to lipid metabolism. Direct
perturbation of these hallmarks in vivo, either by scavenging ROS or by halting
the cyclic mammary cell population expansion, attenuated tumor recurrence.
Finally, these observations were mirrored in transcriptomic and histological
signatures of residual cancer cells from neoadjuvant-treated breast cancer
patients. These results highlight the potential of lipid metabolism and ROS as
therapeutic targets for reducing tumor recurrence in breast cancer patients.
PMID- 28504654
TI - Sugar makes neutrophils RAGE: linking diabetes-associated hyperglycemia to
thrombocytosis and platelet reactivity.
AB - Diabetes mellitus is associated with an increased risk for cardiovascular
disease, but the link between hyperglycemia and atherothrombotic disease is not
completely understood. Patients with diabetes often show hyporesponsiveness to
antiplatelet therapies, and it has been suggested that hyperreactive reticulated
platelets underlie this altered therapeutic response. In this issue of the JCI,
Kraakman et al. uncover a previously unknown link between hyperglycemia and
enhanced platelet production and reactivity. The authors demonstrate that high
blood glucose levels trigger neutrophil release of S100 calcium-binding protein
A8/A9 (S100A8/A9), which binds to the receptor for advanced glycation end
products (RAGE) on Kupffer cells, ultimately leading to increased thrombopoietin
(TPO) production in the liver. TPO causes megakaryocyte proliferation and
increased platelet production. This study demonstrates the importance of glycemic
control and identifies potential therapeutic targets in the normalization of
platelet numbers and function in diabetes.
PMID- 28504655
TI - Transcription factors SOHLH1 and SOHLH2 coordinate oocyte differentiation without
affecting meiosis I.
AB - Following migration of primordial germ cells to the genital ridge, oogonia
undergo several rounds of mitotic division and enter meiosis at approximately
E13.5. Most oocytes arrest in the dictyate (diplotene) stage of meiosis circa
E18.5. The genes necessary to drive oocyte differentiation in parallel with
meiosis are unknown. Here, we have investigated whether expression of
spermatogenesis and oogenesis bHLH transcription factor 1 (Sohlh1) and Sohlh2
coordinates oocyte differentiation within the embryonic ovary. We found that
SOHLH2 protein was expressed in the mouse germline as early as E12.5 and preceded
SOHLH1 protein expression, which occurred circa E15.5. SOHLH1 protein appearance
at E15.5 correlated with SOHLH2 translocation from the cytoplasm into the nucleus
and was dependent on SOHLH1 expression. NOBOX oogenesis homeobox (NOBOX) and LIM
homeobox protein 8 (LHX8), two important regulators of postnatal oogenesis, were
coexpressed with SOHLH1. Single deficiency of Sohlh1 or Sohlh2 disrupted the
expression of LHX8 and NOBOX in the embryonic gonad without affecting meiosis.
Sohlh1-KO infertility was rescued by conditional expression of the Sohlh1
transgene after the onset of meiosis. However, Sohlh1 or Sohlh2 transgene
expression could not rescue Sohlh2-KO infertility due to a lack of Sohlh1 or
Sohlh2 expression in rescued mice. Our results indicate that Sohlh1 and Sohlh2
are essential regulators of oocyte differentiation but do not affect meiosis I.
PMID- 28504656
TI - Effect of IL-1beta, TNF-alpha and IGF-1 on trans-endothelial passage of synthetic
vectors through an in vitro vascular endothelial barrier of striated muscle.
AB - When administrated in the blood circulation, plasmid DNA (pDNA) complexed with
synthetic vectors must pass through a vascular endothelium to transfect
underlying tissues. Under inflammatory condition, cytokines can modify the
endothelium integrity. Here, the trans-endothelial passage (TEP) of DNA complexes
including polyplexes, lipoplexes and lipopolyplexes was investigated in the
presence of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta)
or insulin-like growth factor-1 (IGF-1). The experiments were performed by using
an in vitro model comprising a monolayer of mouse cardiac endothelial cells
(MCEC) seeded on a trans-well insert and the transfection of C2C12 myoblasts
cultured on the lower chamber as read out of TEP. We report that polyplexes made
with a histidinylated derivative of lPEI (His-lPEI) exhibit the highest capacity
(10.5 MUg cm-2 h versus 0.324 MUg cm-2 h) to cross TNF-alpha-induced inflamed
endothelium model, but this positive effect is counterbalanced by the presence of
IL-1beta. His-lPEI polyplex TEP is also increased in the presence of IGF-1 (2.58
MUg cm-2 h). TEP of lipid-based DNA complexes including lipoplexes and
lipopolyplexes was lowest compared with polymer-based DNA complexes. Overall, the
results indicate that under inflammation, His-lPEI polyplexes have a good profile
to cross a vascular endothelium of striated muscle with low cytotoxicity and high
transfection efficiency of C2C12 myoblasts. These data provide insights
concerning the endothelial passage of vectors in inflammatory conditions and can
serve as a basis towards in vivo studies.
PMID- 28504657
TI - Engineering liposomal nanoparticles for targeted gene therapy.
AB - Recent mechanistic studies have attempted to deepen our understanding of the
process by which liposome-mediated delivery of genetic material occurs.
Understanding the interactions between lipid nanoparticles and cells is still
largely elusive. Liposome-mediated delivery of genetic material faces systemic
obstacles alongside entry into the cell, endosomal escape, lysosomal degradation
and nuclear uptake. Rational design approaches for targeted delivery have been
developed to reduce off-target effects and enhance transfection. These
strategies, which have included the modification of lipid nanoparticles with
target-specific ligands to enhance intracellular uptake, have shown significant
promise at the proof-of-concept stage. Control of physical and chemical
specifications of liposome composition, which includes lipid-to-DNA charge, size,
presence of ester bonds, chain length and nature of ligand complexation, is
integral to the performance of targeted liposomes as genetic delivery agents.
Clinical advances are expected to rely on such systems in the therapeutic
application of liposome nanoparticle-based gene therapy. Here, we discuss the
latest breakthroughs in the development of targeted liposome-based agents for the
delivery of genetic material, paying particular attention to new ligand and
cationic lipid design as well as recent in vivo advances.
PMID- 28504658
TI - Cure SMA and our patient community celebrate the first approved drug for SMA.
AB - Cure SMA is dedicated to the treatment and cure of spinal muscular atrophy (SMA)
a disease affecting motor neurons, that robs patients of their ability to walk,
eat and even breathe. Since 1984, we have directed and invested in comprehensive
research that has shaped the scientific community's understanding of SMA. On 23
December, 2016, the Food and Drug Administration (FDA) announced approval of
Spinraza, a treatment developed by Biogen and Ionis, making it the first-ever
approved therapy for SMA. Cure SMA provided early research funding in 2003
leading to the discovery of ISS-N1 sequence, now targeted by Spinraza. We are
pleased that our strategy of providing seed funding for research to either
identify new therapeutic strategies or de-risk early stage ones, has proven
successful with Spinraza's approval. The approval of Spinraza provides great hope
to the SMA community and represents decades of hard work and perseverance by
families, researchers, pharmaceutical companies and the FDA. Our hope is that
Spinraza is the leading edge of a robust drug pipeline, and with our deep
expertise in every aspect of SMA, we remain committed to do everything we can to
support research and drug development to achieve the greatest possible effect for
each and every SMA patient.
PMID- 28504660
TI - Physiological evolution: Genomic redox footprints.
PMID- 28504659
TI - Structure of the MacAB-TolC ABC-type tripartite multidrug efflux pump.
AB - The MacA-MacB-TolC assembly of Escherichia coli is a transmembrane machine that
spans the cell envelope and actively extrudes substrates, including macrolide
antibiotics and polypeptide virulence factors. These transport processes are
energized by the ATPase MacB, a member of the ATP-binding cassette (ABC)
superfamily. We present an electron cryo-microscopy structure of the ABC-type
tripartite assembly at near-atomic resolution. A hexamer of the periplasmic
protein MacA bridges between a TolC trimer in the outer membrane and a MacB dimer
in the inner membrane, generating a quaternary structure with a central channel
for substrate translocation. A gating ring found in MacA is proposed to act as a
one-way valve in substrate transport. The MacB structure features an atypical
transmembrane domain with a closely packed dimer interface and a periplasmic
opening that is the likely portal for substrate entry from the periplasm, with
subsequent displacement through an allosteric transport mechanism.
PMID- 28504661
TI - Circulating tumor cells as a biomarker for response to therapy in multiple
myeloma patients treated within the GMMG-MM5 trial.
PMID- 28504662
TI - Association between pretransplant iron overload determined by bone marrow
pathological analysis and bacterial infection.
PMID- 28504663
TI - A new time-dependent approach for assessment of the impact of invasive
aspergillosis shows effect on short- but not on long-term survival of patients
with AML or high-risk MDS.
AB - Invasive aspergillosis (IA) has been reported to yield high mortality rates.
Patients with an unfavourable prognostic haematological disease not only have a
higher probability of developing IA but are also more likely to die due to causes
directly related to the underlying disease. This complexity of risk mechanisms
confounds the causal interpretation of IA occurrence and mortality. Full
consideration of the changing patient characteristics over time is necessary to
obtain reliable estimates of the correlation of IA with mortality. We studied the
effect of IA on mortality in 167 consecutive patients starting with remission
induction therapy for AML or of whom most patients continued to haematopoietic
stem cell transplantation (HSCT). No standard antifungal prophylaxis was
administered in the period before HSCT. Survival analyses were performed to
determine risk estimates of IA for different phases of treatment before and after
HSCT. Time-dependent adjustment for confounding variables was performed using Cox
proportional hazards models. In 55 of 167 enroled patients, IA was diagnosed.
Before HSCT, adjusted hazard ratios and 95% confidence intervals on mortality
after the diagnosis of IA were 3.5 (1.7-7.5), 2.0 (0.69-5.9), 2.3 (0.79-6.8) and
0.80 (0.49-1.4) within 30 days, between 30 and 60 days, between 60 and 90 days or
more than 90 days, respectively. A similar pattern was observed after HSCT. The
occurrence of IA did not significantly influence the decision to follow through
with HSCT. The results provide new insights in short- and long-term survival of
patients diagnosed with IA. A significantly increased mortality risk was only
observed in the first month after diagnosis of IA. No unfavourable association
with mortality was observed in the later course of treatment. The occurrence of
IA did not affect the probability of attaining HSCT in our population.
PMID- 28504665
TI - Upper GI GVHD: similar outcomes to other grade II graft-versus-host disease.
AB - The significance of upper gastrointestinal tract (UGI) acute GVHD (aGVHD)
compared with other grade II aGVHD is not clearly defined. We compared the
outcomes of patients with grade II aGVHD with or without biopsy-proven UGI
involvement in three groups: grade II aGVHD without UGI (n=178), grade II aGVHD
with UGI and other sites (n=102) and isolated UGI aGVHD (n=32). The overall
response (ORR) to steroids at day 28 differed among the three groups (76, 67 and
91%, respectively, P=0.01), but was only marginally different in direct
comparison with those without or with UGI aGVHD (P=0.07) or with isolated UGI
aGVHD (P=0.06). In multivariate analysis, as compared with grade II aGVHD
patients without UGI involvement, those with UGI involvement and those with
isolated UGI aGVHD had similar risks of chronic GVHD, relapse and non-relapse
mortality and similar disease-free survival and overall survival. Our data
suggest that patients with UGI aGVHD have similar outcomes as those without UGI
involvement, supporting the view that UGI aGVHD should still be included as a
grade II-defining event.
PMID- 28504664
TI - Pre-transplant ferritin, albumin and haemoglobin are predictive of survival
outcome independent of disease risk index following allogeneic stem cell
transplantation.
AB - Prognostic biomarkers are useful in allogeneic stem cell transplantation (SCT) to
predict survival and relapse outcomes. We sought to derive a prognostic scoring
system, which augmented the predictive power of the disease risk index (DRI) by
incorporating biomarkers and validating their significance after SCT. The
outcomes of overall survival (OS) and relapse were assessed with non-relapse
mortality (NRM) treated as a competing risk to relapse. Six hundred and two
patients were identified through a retrospective analysis of allogeneic SCT
recipients for haematological malignancy between 2000 and 2013 in a single
centre. Multivariate analysis confirmed the significant predictors of OS pre-SCT
were serum ferritin >1000 MUg/L (hazard ratio (HR) 1.94, 95% comorbidity index
(CI): 1.44-2.60), Hb <100 g/L (HR 1.71, 95% CI: 1.27-2.30) and albumin <30 g/L
(HR 2.65, 95% CI: 1.30-5.40). In combination with DRI, these biomarkers
significantly improved the Harrell's C statistic (excluding biomarkers: C=0.60,
95% CI: 0.57-0.64; with biomarkers: C=0.65, 95% CI: 0.62-0.69, P<0.001). Four
prognostic groups were derived at the pre-SCT time point: Group 1 (Scores 0-1,
n=180, HR=1 (ref)), Group 2 (Scores 2-5, n=298, HR 2.7, 95% CI: 1.8-3.9), Group 3
(Scores 6-7, n=87, HR 4.5, 95% CI: 3.0-6.9) and Group 4 (scores 8-10, n=9, HR
13.4, 95% CI: 5.9-30.2). These prognostic models were also predictive of relapse
and NRM and remained valid at day 100, 12 months and 24 months post SCT.
PMID- 28504666
TI - Conditioning regimens for allogeneic hematopoietic stem cell transplants in acute
myeloid leukemia.
AB - AML is currently the first indication for allogeneic hematopoietic stem cell
transplantation (allo-HSCT), as shown by international transplant registries. The
conditioning regimens are classified as myeloablative conditioning, non
myeloablative or reduced intensity conditioning. Targeted radioimmunotherapy such
as anti-CD45 antibody have also been added to the conditioning regimen in an
attempt to improve tumor cell kill. Refinement of standard regimens has led to a
reduction of non-relapse mortality, also in the older age group over 60 or 70
years of age. Relapse post allo-HSCT remains an important issue, especially for
patients who undergo transplant with residual or refractory disease. In these
patients, pre- and post-transplant interventions need to be considered.
PMID- 28504667
TI - Rapid cloning of genes in hexaploid wheat using cultivar-specific long-range
chromosome assembly.
AB - Cereal crops such as wheat and maize have large repeat-rich genomes that make
cloning of individual genes challenging. Moreover, gene order and gene sequences
often differ substantially between cultivars of the same crop species. A major
bottleneck for gene cloning in cereals is the generation of high-quality sequence
information from a cultivar of interest. In order to accelerate gene cloning from
any cropping line, we report 'targeted chromosome-based cloning via long-range
assembly' (TACCA). TACCA combines lossless genome-complexity reduction via
chromosome flow sorting with Chicago long-range linkage to assemble complex
genomes. We applied TACCA to produce a high-quality (N50 of 9.76 Mb) de novo
chromosome assembly of the wheat line CH Campala Lr22a in only 4 months. Using
this assembly we cloned the broad-spectrum Lr22a leaf-rust resistance gene, using
molecular marker information and ethyl methanesulfonate (EMS) mutants, and found
that Lr22a encodes an intracellular immune receptor homologous to the Arabidopsis
thaliana RPM1 protein.
PMID- 28504668
TI - HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by
NK cells.
AB - Polymorphisms in the human leukocyte antigen (HLA) class I genes can cause the
rejection of pluripotent stem cell (PSC)-derived products in allogeneic
recipients. Disruption of the Beta-2 Microglobulin (B2M) gene eliminates surface
expression of all class I molecules, but leaves the cells vulnerable to lysis by
natural killer (NK) cells. Here we show that this 'missing-self' response can be
prevented by forced expression of minimally polymorphic HLA-E molecules. We use
adeno-associated virus (AAV)-mediated gene editing to knock in HLA-E genes at the
B2M locus in human PSCs in a manner that confers inducible, regulated, surface
expression of HLA-E single-chain dimers (fused to B2M) or trimers (fused to B2M
and a peptide antigen), without surface expression of HLA-A, B or C. These HLA
engineered PSCs and their differentiated derivatives are not recognized as
allogeneic by CD8+ T cells, do not bind anti-HLA antibodies and are resistant to
NK-mediated lysis. Our approach provides a potential source of universal donor
cells for applications where the differentiated derivatives lack HLA class II
expression.
PMID- 28504669
TI - Nitric oxide prevents a pathogen-permissive granulocytic inflammation during
tuberculosis.
AB - Nitric oxide contributes to protection from tuberculosis. It is generally assumed
that this protection is due to direct inhibition of Mycobacterium tuberculosis
growth, which prevents subsequent pathological inflammation. In contrast, we
report that nitric oxide primarily protects mice by repressing an interleukin-1-
and 12/15-lipoxygenase-dependent neutrophil recruitment cascade that promotes
bacterial replication. Using M. tuberculosis mutants as indicators of the
pathogen's environment, we inferred that granulocytic inflammation generates a
nutrient-replete niche that supports M. tuberculosis growth. Parallel clinical
studies indicate that a similar inflammatory pathway promotes tuberculosis in
patients. The human 12/15-lipoxygenase orthologue, ALOX12, is expressed in
cavitary tuberculosis lesions; the abundance of its products correlates with the
number of airway neutrophils and bacterial burden and a genetic polymorphism that
increases ALOX12 expression is associated with tuberculosis risk. These data
suggest that M. tuberculosis exploits neutrophilic inflammation to preferentially
replicate at sites of tissue damage that promote contagion.
PMID- 28504670
TI - Longevity of major coenzymes allows minimal de novo synthesis in microorganisms.
AB - Coenzymes are vital for cellular metabolism and act on the full spectrum of
enzymatic reactions. Intrinsic chemical reactivity, enzyme promiscuity and high
flux through their catalytic cycles make coenzymes prone to damage. To counteract
such compromising factors and ensure stable levels of functional coenzymes, cells
use a complex interplay between de novo synthesis, salvage, repair and
degradation. However, the relative contribution of these factors is currently
unknown, as is the overall stability of coenzymes in the cell. Here, we use
dynamic 13C-labelling experiments to determine the half-life of major coenzymes
of Escherichia coli. We find that coenzymes such as pyridoxal 5-phosphate,
flavins, nicotinamide adenine dinucleotide (phosphate) and coenzyme A are
remarkably stable in vivo and allow biosynthesis close to the minimal necessary
rate. In consequence, they are essentially produced to compensate for dilution by
growth and passed on over generations of cells. Exceptions are antioxidants,
which are short-lived, suggesting an inherent requirement for increased renewal.
Although the growth-driven turnover of stable coenzymes is apparently subject to
highly efficient end-product homeostasis, we exemplify that coenzyme pools are
propagated in excess in relation to actual growth requirements. Additional
testing of Bacillus subtilis and Saccharomyces cerevisiae suggests that coenzyme
longevity is a conserved feature in biology.
PMID- 28504671
TI - Reduced sensory synaptic excitation impairs motor neuron function via Kv2.1 in
spinal muscular atrophy.
AB - Behavioral deficits in neurodegenerative diseases are often attributed to the
selective dysfunction of vulnerable neurons via cell-autonomous mechanisms.
Although vulnerable neurons are embedded in neuronal circuits, the contributions
of their synaptic partners to disease process are largely unknown. Here we show
that, in a mouse model of spinal muscular atrophy (SMA), a reduction in
proprioceptive synaptic drive leads to motor neuron dysfunction and motor
behavior impairments. In SMA mice or after the blockade of proprioceptive
synaptic transmission, we observed a decrease in the motor neuron firing that
could be explained by the reduction in the expression of the potassium channel
Kv2.1 at the surface of motor neurons. Chronically increasing neuronal activity
pharmacologically in vivo led to a normalization of Kv2.1 expression and an
improvement in motor function. Our results demonstrate a key role of excitatory
synaptic drive in shaping the function of motor neurons during development and
the contribution of its disruption to a neurodegenerative disease.
PMID- 28504672
TI - Identification of a motor-to-auditory pathway important for vocal learning.
AB - Learning to vocalize depends on the ability to adaptively modify the temporal and
spectral features of vocal elements. Neurons that convey motor-related signals to
the auditory system are theorized to facilitate vocal learning, but the identity
and function of such neurons remain unknown. Here we identify a previously
unknown neuron type in the songbird brain that transmits vocal motor signals to
the auditory cortex. Genetically ablating these neurons in juveniles disrupted
their ability to imitate features of an adult tutor's song. Ablating these
neurons in adults had little effect on previously learned songs but interfered
with their ability to adaptively modify the duration of vocal elements and
largely prevented the degradation of songs' temporal features that is normally
caused by deafening. These findings identify a motor to auditory circuit
essential to vocal imitation and to the adaptive modification of vocal timing.
PMID- 28504673
TI - A fluoro-Nissl dye identifies pericytes as distinct vascular mural cells during
in vivo brain imaging.
AB - Pericytes and smooth muscle cells are integral components of the brain
microvasculature. However, no techniques exist to unambiguously identify these
cell types, greatly limiting their investigation in vivo. Here we show that the
fluorescent Nissl dye NeuroTrace 500/525 labels brain pericytes with specificity,
allowing high-resolution optical imaging in the live mouse. We demonstrate that
capillary pericytes are a population of mural cells with distinct morphological,
molecular and functional features that do not overlap with precapillary or
arteriolar smooth muscle actin-expressing cells. The remarkable specificity for
dye uptake suggests that pericytes have molecular transport mechanisms not
present in other brain cells. We demonstrate feasibility of longitudinal pericyte
imaging during microvascular development and aging and in models of brain
ischemia and Alzheimer's disease. The ability to easily label pericytes in any
mouse model opens the possibility of a broad range of investigations of mural
cells in vascular development, neurovascular coupling and neuropathology.
PMID- 28504674
TI - Printable elastic conductors by in situ formation of silver nanoparticles from
silver flakes.
AB - Printable elastic conductors promise large-area stretchable sensor/actuator
networks for healthcare, wearables and robotics. Elastomers with metal
nanoparticles are one of the best approaches to achieve high performance, but
large-area utilization is limited by difficulties in their processability. Here
we report a printable elastic conductor containing Ag nanoparticles that are
formed in situ, solely by mixing micrometre-sized Ag flakes, fluorine rubbers,
and surfactant. Our printable elastic composites exhibit conductivity higher than
4,000 S cm-1 (highest value: 6,168 S cm-1) at 0% strain, and 935 S cm-1 when
stretched up to 400%. Ag nanoparticle formation is influenced by the surfactant,
heating processes, and elastomer molecular weight, resulting in a drastic
improvement of conductivity. Fully printed sensor networks for stretchable robots
are demonstrated, sensing pressure and temperature accurately, even when
stretched over 250%.
PMID- 28504675
TI - Giant thermal Hall effect in multiferroics.
AB - Multiferroics, in which dielectric and magnetic orders coexist and couple with
each other, attract renewed interest for their cross-correlated phenomena,
offering a fundamental platform for novel functionalities. Elementary excitations
in such systems are strongly affected by the lattice-spin interaction, as
exemplified by the electromagnons and the magneto-thermal transport. Here we
report an unprecedented coupling between magnetism and phonons in multiferroics,
namely, the giant thermal Hall effect. The thermal transport of insulating polar
magnets (ZnxFe1-x)2Mo3O8 is dominated by phonons, yet extremely sensitive to the
magnetic structure. In particular, large thermal Hall conductivities are observed
in the ferrimagnetic phase, indicating unconventional lattice-spin interactions
and a new mechanism for the Hall effect in insulators. Our results show that the
thermal Hall effect in multiferroic materials can be an effective probe for
strong lattice-spin interactions and provide a new tool for magnetic control of
thermal currents.
PMID- 28504676
TI - Developing Spindlin1 small-molecule inhibitors by using protein microarrays.
AB - The discovery of inhibitors of methyl- and acetyl-binding domains has provided
evidence for the 'druggability' of epigenetic effector molecules. The small
molecule probe UNC1215 prevents methyl-dependent protein-protein interactions by
engaging the aromatic cage of MBT domains and, with lower affinity, Tudor
domains. Using a library of tagged UNC1215 analogs, we screened a protein-domain
microarray of human methyllysine effector molecules to rapidly detect compounds
with new binding profiles with either increased or decreased specificity. Using
this approach, we identified a compound (EML405) that acquired a novel
interaction with the Tudor-domain-containing protein Spindlin1 (SPIN1).
Structural studies facilitated the rational synthesis of SPIN1 inhibitors with
increased selectivity (EML631-633), which engage SPIN1 in cells, block its
ability to 'read' H3K4me3 marks and inhibit its transcriptional-coactivator
activity. Protein microarrays can thus be used as a platform to 'target-hop' and
identify small molecules that bind and compete with domain-motif interactions.
PMID- 28504677
TI - beta-Lactone formation during product release from a nonribosomal peptide
synthetase.
AB - Nonribosomal peptide synthetases (NRPSs) are multidomain modular biosynthetic
assembly lines that polymerize amino acids into a myriad of biologically active
nonribosomal peptides (NRPs). NRPS thioesterase (TE) domains employ diverse
release strategies for off-loading thioester-tethered polymeric peptides from
termination modules typically via hydrolysis, aminolysis, or cyclization to
provide mature antibiotics as carboxylic acids/esters, amides, and
lactams/lactones, respectively. Here we report the enzyme-catalyzed formation of
a highly strained beta-lactone ring during TE-mediated cyclization of a beta
hydroxythioester to release the antibiotic obafluorin (Obi) from an NRPS assembly
line. The Obi NRPS (ObiF) contains a type I TE domain with a rare catalytic
cysteine residue that plays a direct role in beta-lactone ring formation. We
present a detailed genetic and biochemical characterization of the entire Obi
biosynthetic gene cluster in plant-associated Pseudomonas fluorescens ATCC 39502
that establishes a general strategy for beta-lactone biogenesis.
PMID- 28504678
TI - A conserved threonine prevents self-intoxication of enoyl-thioester reductases.
AB - Enzymes are highly specific biocatalysts, yet they can promote unwanted side
reactions. Here we investigated the factors that direct catalysis in the enoyl
thioester reductase Etr1p. We show that a single conserved threonine is essential
to suppress the formation of a side product that would otherwise act as a high
affinity inhibitor of the enzyme. Substitution of this threonine with isosteric
valine increases side-product formation by more than six orders of magnitude,
while decreasing turnover frequency by only one order of magnitude. Our results
show that the promotion of wanted reactions and the suppression of unwanted side
reactions operate independently at the active site of Etr1p, and that the active
suppression of side reactions is highly conserved in the family of medium-chain
dehydrogenases/reductases (MDRs). Our discovery emphasizes the fact that the
active destabilization of competing transition states is an important factor
during catalysis that has implications for the understanding and the de novo
design of enzymes.
PMID- 28504680
TI - Nm-seq maps 2'-O-methylation sites in human mRNA with base precision.
AB - The ribose of RNA nucleotides can be 2'-O-methylated (Nm). Despite advances in
high-throughput detection, the inert chemical nature of Nm still limits
sensitivity and precludes mapping in mRNA. We leveraged the differential
reactivity of 2'-O-methylated and 2'-hydroxylated nucleosides to periodate
oxidation to develop Nm-seq, a sensitive method for transcriptome-wide mapping of
Nm with base precision. Nm-seq uncovered thousands of Nm sites in human mRNA with
features suggesting functional roles.
PMID- 28504681
TI - Fused cerebral organoids model interactions between brain regions.
AB - Human brain development involves complex interactions between different regions,
including long-distance neuronal migration or formation of major axonal tracts.
Different brain regions can be cultured in vitro within 3D cerebral organoids,
but the random arrangement of regional identities limits the reliable analysis of
complex phenotypes. Here, we describe a coculture method combining brain regions
of choice within one organoid tissue. By fusing organoids of dorsal and ventral
forebrain identities, we generate a dorsal-ventral axis. Using fluorescent
reporters, we demonstrate CXCR4-dependent GABAergic interneuron migration from
ventral to dorsal forebrain and describe methodology for time-lapse imaging of
human interneuron migration. Our results demonstrate that cerebral organoid
fusion cultures can model complex interactions between different brain regions.
Combined with reprogramming technology, fusions should offer researchers the
possibility to analyze complex neurodevelopmental defects using cells from
neurological disease patients and to test potential therapeutic compounds.
PMID- 28504679
TI - Generation of pure GABAergic neurons by transcription factor programming.
AB - Approaches to differentiating pluripotent stem cells (PSCs) into neurons
currently face two major challenges-(i) generated cells are immature, with
limited functional properties; and (ii) cultures exhibit heterogeneous neuronal
subtypes and maturation stages. Using lineage-determining transcription factors,
we previously developed a single-step method to generate glutamatergic neurons
from human PSCs. Here, we show that transient expression of the transcription
factors Ascl1 and Dlx2 (AD) induces the generation of exclusively GABAergic
neurons from human PSCs with a high degree of synaptic maturation. These AD
induced neuronal (iN) cells represent largely nonoverlapping populations of
GABAergic neurons that express various subtype-specific markers. We further used
AD-iN cells to establish that human collybistin, the loss of gene function of
which causes severe encephalopathy, is required for inhibitory synaptic function.
The generation of defined populations of functionally mature human GABAergic
neurons represents an important step toward enabling the study of diseases
affecting inhibitory synaptic transmission.
PMID- 28504682
TI - Testing for differential abundance in mass cytometry data.
AB - When comparing biological conditions using mass cytometry data, a key challenge
is to identify cellular populations that change in abundance. Here, we present a
computational strategy for detecting 'differentially abundant' populations by
assigning cells to hyperspheres, testing for significant differences between
conditions and controlling the spatial false discovery rate. Our method
(http://bioconductor.org/packages/cydar) outperforms other approaches in
simulations and finds novel patterns of differential abundance in real data.
PMID- 28504683
TI - Normalizing single-cell RNA sequencing data: challenges and opportunities.
AB - Single-cell transcriptomics is becoming an important component of the molecular
biologist's toolkit. A critical step when analyzing data generated using this
technology is normalization. However, normalization is typically performed using
methods developed for bulk RNA sequencing or even microarray data, and the
suitability of these methods for single-cell transcriptomics has not been
assessed. We here discuss commonly used normalization approaches and illustrate
how these can produce misleading results. Finally, we present alternative
approaches and provide recommendations for single-cell RNA sequencing users.
PMID- 28504684
TI - Fully automated 5-plex fluorescent immunohistochemistry with tyramide signal
amplification and same species antibodies.
AB - The ability to simultaneously visualize the presence, abundance, location and
functional state of many targets in cells and tissues has been described as a
true next-generation approach in immunohistochemistry (IHC). A typical
requirement for multiplex IHC (mIHC) is the use of different animal species for
each primary (1 degrees Ab) and secondary (2 degrees Ab) antibody pair. Although
1 degrees Abs from different species have been used with differently labeled
species-specific 2 degrees Abs, quite often the appropriate combination of
antibodies is not available. More recently, sequential detection of multiple
antigens using 1 degrees Abs from the same species used a microwaving treatment
between successive antigen detection cycles to elute previously bound 1 degrees
Ab/2 degrees Ab complex and therefore to prevent the cross-reactivity of anti
species 2 degrees Abs used in subsequent detection cycles. We present here a
fully automated 1 degrees Ab/2 degrees Ab complex heat deactivation (HD) method
on Ventana's BenchMark ULTRA slide stainer. This method is applied to detection
using fluorophore-conjugated tyramide deposited on the tissue and takes advantage
of the strong covalent bonding of the detection substrate to the tissue,
preventing its elution in the HD process. The HD process was characterized for
(1) effectiveness in preventing Ab cross-reactivity, (2) impact on the epitopes
and (3) impact on the fluorophores. An automated 5-plex fluorescent IHC assay was
further developed using the HD method and rabbit 1 degrees Abs for CD3, CD8,
CD20, CD68 and FoxP3 immune biomarkers in human tissue specimens. The
fluorophores were carefully chosen and the narrow-band filters were designed to
allow visualization of the staining under fluorescent microscope with minimal
bleed through. The automated 5-plex fluorescent IHC assay achieved staining
results comparable to the respective single-plex chromogenic IHC assays. This
technology enables automated mIHC using unmodified 1 degrees Abs from same
species and the corresponding anti-species 2 degrees Ab on a clinically
established automated platform to ensure staining quality, reliability and
reproducibility.
PMID- 28504685
TI - Spleen-derived lipocalin-2 in the portal vein regulates Kupffer cells activation
and attenuates the development of liver fibrosis in mice.
AB - The liver has an immune tolerance against gut-derived products from the portal
vein (PV). A disruption of the gut-liver axis leads to liver injury and fibrosis.
The spleen is connected to the PV and regulates immune functions. However,
possible splenic effects on liver fibrosis development are unclear. Lipocalin-2
(Lcn2) is an antimicrobial protein that regulates macrophage activation. To
clarify the role of the spleen in liver fibrosis development, we induced liver
fibrosis in mice after splenectomy, and investigated liver fibrosis development.
Liver fibrosis resulted in significantly increased splenic Lcn2 levels, but all
other measured cytokine levels were unchanged. Splenectomized mice showed
enhanced liver fibrosis and inflammation accompanied by significantly decreased
Lcn2 levels in PV. Lipopolysaccharide-stimulated primary Kupffer cells, resident
liver macrophages, which were treated with recombinant Lcn2 (rLcn2) produced less
tumor necrosis factor-alpha and Ccl2 and the activation of hepatic stellate
cells, the effector cells for collagen production in the liver, was suppressed by
co-culture with rLcn2-treated Kupffer cells. In addition, the involvement of gut
derived products in splenectomized mice was evaluated by gut sterilization.
Interestingly, gut sterilization blocked the effect of splenectomy on liver
fibrosis development. In conclusion, spleen deficiency accelerated liver fibrosis
development and decreased PV Lcn2 levels. The mechanism of splenic protection
against liver fibrosis development may involve the splenic Lcn2, triggered by gut
derived products that enter the liver through the PV, regulates Kupffer cells
activated by the gut-liver axis. Thus, the splenic Lcn2 may have an important
role in regulating the immune tolerance of the liver in liver fibrosis
development.
PMID- 28504686
TI - NDGA-P21, a novel derivative of nordihydroguaiaretic acid, inhibits glioma cell
proliferation and stemness.
AB - Nordihydroguaiaretic acid (NDGA) and its synthetic chiral analog dl
nordihydroguaiaretic acid (Nordy) show collective benefits in anti-tumor, and
defending against viral and bacterial infections. Here, we synthetized a new
derivative-NDGA-P21 based on NDGA structure. Regardless of the structural
similarity, NDGA-P21 exhibited stronger capability in suppression of glioblastoma
(GBM) cell growth as compared to Nordy. Mechanically, NDGA-P21 is able to arrest
cell cycle of GBM cells in G0/G1 phase, and to block cell proliferation
sequentially. It is important to note that NDGA-P21 is able to impair the
stemness of glioma stem-like cells (GSLCs) via measurement of colony formation
and sphere formation. Taken together, the novel NDGA-based compound NDGA-P21
exhibits potential therty -20 apeutic implications through inhibiting
proliferation of glioma cells and self-renewal capability of GSLCs.
PMID- 28504687
TI - The kinesin KIF14 is overexpressed in medulloblastoma and downregulation of KIF14
suppressed tumor proliferation and induced apoptosis.
AB - Medulloblastoma (MB) is the most common malignant brain tumor in childhood. At
present, there is no well-established targeted drug for majority of patients. The
kinesin family member 14 (KIF14) is a novel oncogene located on chromosome 1q and
is dysregulated in multiple cancers. The objectives of this study were to
evaluate KIF14 expression and chromosome 1q copy number in MB, and to delineate
its biological functions in MB pathogenesis. By quantitative RT-PCR and
immunohistochemistry, we found KIF14 was overexpressed in MB. Increased KIF14
expression at protein level was strongly associated with shorter progression-free
survival (P=0.0063) and overall survival (P=0.0083). Fluorescence in situ
hybridization (FISH) analysis confirmed genomic gain of chromosome 1q in 17/93
(18.3%) of MB. Combined genetic and immunohistochemical analyses revealed that
76.5% of MB with 1q gain showed consistent overexpression of KIF14, and a tight
link between chromosome 1q gain and KIF14 overexpression (P=0.03). Transient,
siRNAs-mediated downregulation of KIF14 suppressed cell proliferation and induced
apoptosis in two MB cell lines. Stably KIF14 knockdown by shRNAs inhibited cell
viability, colony formation, migration and invasion, and tumor sphere formation
in MB cells. We conclude that KIF14 is dysregulated in MB and is an adverse
prognostic factor for survival. Furthermore, KIF14 is part of MB biology and is a
potential therapeutic target for MB.
PMID- 28504689
TI - Molecular signaling in multiple myeloma: association of RAS/RAF mutations and
MEK/ERK pathway activation.
AB - Multiple myeloma (MM) is a plasma cell malignancy that is still considered to be
incurable in most cases. A dominant mutation cluster has been identified in
RAS/RAF genes, emphasizing the potential significance of RAS/RAF/MEK/ERK
signaling as a therapeutic target. As yet, however, the clinical relevance of
this finding is unclear as clinical responses to MEK inhibition in RAS-mutant MM
have been mixed. We therefore assessed RAS/RAF mutation status and MEK/ERK
pathway activation by both targeted sequencing and phospho-ERK
immunohistochemistry in 180 tissue biopsies from 103 patients with newly
diagnosed MM (NDMM) and 77 patients with relapsed/refractory MM (rrMM). We found
a significant enrichment of RAS/BRAF mutations in rrMM compared to NDMM
(P=0.011), which was mainly due to an increase of NRAS mutations (P=0.010). As
expected, BRAF mutations were significantly associated with activated downstream
signaling. However, only KRAS and not NRAS mutations were associated with pathway
activation compared to RAS/BRAFwt (P=0.030). More specifically, only KRASG12D and
BRAFV600E were consistently associated with ERK activation (P<0.001 and P=0.006,
respectively). Taken together, these results suggest the need for a more specific
stratification strategy consisting of both confirmation of protein-level pathway
activation as well as detailed RAS/RAF mutation status to allow for a more
precise and more effective application of targeted therapies, for example, with
BRAF/MEK inhibitors in MM.
PMID- 28504688
TI - Accelerated atherosclerosis development in C57Bl6 mice by overexpressing AAV
mediated PCSK9 and partial carotid ligation.
AB - Studying the role of a particular gene in atherosclerosis typically requires a
time-consuming and often difficult process of generating double knockouts or
transgenics on ApoE-/- or LDL receptor (LDLR)-/- background. Recently, it was
reported that adeno-associated-virus-8 (AAV8)-mediated overexpression of PCSK9
(AAV8-PCSK9) rapidly induced hyperlipidemia. However, using this method in C57BL6
wild-type (C57) mice, it took ~3 months to develop atherosclerosis. Our partial
carotid ligation model is used to rapidly develop atherosclerosis by inducing
disturbed flow in the left common carotid artery within 2 weeks in ApoE-/- or
LDLR-/- mice. Here, we combined these two approaches to develop an accelerated
model of atherosclerosis in C57 mice. C57 mice were injected with AAV9-PCSK9 or
AAV9-luciferase (control) and high-fat diet was initiated. A week later, partial
ligation was performed. Compared to the control, AAV-PCSK9 led to elevated serum
PCSK9, hypercholesterolemia, and rapid atherosclerosis development within 3 weeks
as determined by gross plaque imaging, and staining with Oil-Red-O, Movat's
pentachrome, and CD45 antibody. These plaque lesions were comparable to the
atherosclerotic lesions that have been previously observed in ApoE-/- or LDLR-/-
mice that were subjected to partial carotid ligation and high-fat diet. Next, we
tested whether our method can be utilized to rapidly determine the role of a
particular gene in atherosclerosis. Using eNOS-/- and NOX1-/y mice on C57
background, we found that the eNOS-/- mice developed more advanced lesions, while
the NOX1-/y mice developed less atherosclerotic lesions as compared to the C57
controls. These results are consistent with the previous findings using double
knockouts (eNOS-/-_ApoE-/- and NOX1-/y_ApoE-/-). AAV9-PCSK9 injection followed by
partial carotid ligation is an effective and time-saving approach to rapidly
induce atherosclerosis. This accelerated model is well-suited to quickly
determine the role of gene(s) interest without generating double or triple
knockouts.
PMID- 28504690
TI - MicroRNA-645 is an oncogenic regulator in colon cancer.
AB - Despite advances in early diagnosis and the development of molecularly targeted
therapy, curative treatment of colon cancer once it has metastasized is yet to be
accomplished. This is closely associated with deregulated CRC cell proliferation
and resistance to apoptosis. Here we reveal that upregulation of microRNA-645
(miR-645) through DNA copy number gain is responsible for enhanced proliferation
and resistance to apoptosis in colon cancer. MiR-645 was upregulated in most
colon cancer tissues related to adjacent normal mucosa. This appeared to be
associated with amplification of a section of chromosome 20q13.13, where miR-645
is located. Inhibition of miR-645 reduced proliferation and enhanced sensitivity
to apoptosis triggered by the chemotherapeutic drugs 5-fluorouracil and cisplatin
in CRC cells, and retarded colon cancer xenograft growth. Conversely,
overexpression of miR-645 in normal colon epithelial cells enhanced proliferation
and triggered anchorage-independent cell growth. Although SRY-related HMG-box 30
(SOX30) was identified as a miR-645 target, its expression was only partially
affected by miR-645, suggesting that miR-645 is a fine-tuning mechanism of SOX30
expression. Moreover, overexpression of SOX30 only moderately inhibited promotion
of CRC cell proliferation by miR-645, indicating that miR-645 may have more
targets that contribute to its pro-proliferation effect in colon cancer.
Together, this study reveals that miR-645 can regulate oncogenesis in colon
cancer with SOX30 being one of its targets.
PMID- 28504691
TI - CXCR3 mediates ascites-directed tumor cell migration and predicts poor outcome in
ovarian cancer patients.
AB - Intraabdominal tumor dissemination is a major hallmark of epithelial ovarian
cancer (EOC), but the underlying mechanisms have not been fully elucidated. The
CXCR3 chemokine receptor supports migration of tumor cells to metastatic sites,
but its role in ovarian cancer metastasis is largely unknown. Herein, we first
screened two independent cohorts of high-grade serous ovarian cancers (HGSCs,
discovery set n=60, validation set n=117) and 102 metastatic lesions for CXCR3
expression. In primary tumors, CXCR3 was particularly overexpressed by tumor
cells at the invasive front. In intraabdominal metastases, tumor cells revealed a
strong CXCR3 expression regardless of its expression in the corresponding primary
tumor, suggesting a selection of CXCR3-overexpressing cancer cells into
peritoneal niches. In support of this, CXCR3 mediated the migration of tumor cell
lines OVCAR3 and SKOV3 toward malignant ascites, which was inhibited by a
monoclonal anti-CXCR3 antibody in vitro. These results were prospectively
validated in ascites-derived tumor cells from EOC patients ex vivo (n=9).
Moreover, tumor cell-associated overexpression of CXCR3 in advanced ovarian
cancer patients was associated with a reduced progression-free survival (PFS) and
overall survival (OS), which remained independent of optimal debulking, age, FIGO
stage and lymph node involvement (PFS: hazard ratio (HR) 2.11, 95% confidence
interval (CI) 1.30-3.45, P=0.003; OS: HR 2.36, 95% CI 1.50-3.71, P<0.001). These
results in ovarian cancer patients identify CXCR3 as a potential new target to
confine peritoneal spread in ovarian cancer after primary cytoreductive surgery.
PMID- 28504692
TI - Mint3-mediated L1CAM expression in fibroblasts promotes cancer cell proliferation
via integrin alpha5beta1 and tumour growth.
AB - Fibroblasts are some of the major cells in tumour tissues that influence tumour
progression and drug resistance. However, our understanding on fibroblast
mediated tumour malignancy remains incomplete. Munc18-1-interacting protein 3
(Mint3) is known as an activator of hypoxia-inducible factor-1 (HIF-1) even
during normoxia in cancer cells, macrophages and fibroblasts. Although Mint3
promotes ATP production via glycolysis by activating HIF-1 in cancer cells and
macrophages, the biological role of Mint3-mediated HIF-1 activation in
fibroblasts remains unclear. To address this, we examined whether Mint3 in
fibroblasts contributes to tumour growth. Mint3 depletion in mouse embryonic
fibroblasts (MEFs) decreased tumour growth of co-injected human breast cancer
cells, MDA-MB-231 and epidermoid carcinoma A431 cells in mice. In MEFs, Mint3
also promoted cancer cell proliferation in vitro in a cell-cell contact-dependent
manner. Mint3-mediated cancer cell proliferation depended on HIF-1, and further
gene expression analysis revealed that the cell adhesion molecule, L1 cell
adhesion molecule (L1CAM), was induced by Mint3 and HIF-1 in fibroblasts. Mint3
mediated L1CAM expression in fibroblasts stimulated the ERK signalling pathway
via integrin alpha5beta1 in cancer cells, and promoted cancer cell proliferation
in vitro and tumour growth. In cancer-associated fibroblasts (CAFs), knockdown of
MT1-MMP, which promotes Mint3-mediated HIF-1 activation, or Mint3 decreased L1CAM
expression. As MEFs, CAFs also promoted cancer cell proliferation in vitro, and
tumour growth via Mint3 and L1CAM. In human breast cancer specimens, the number
of fibroblasts expressing L1CAM, Mint3 and MT1-MMP was higher in cancer regions
than in adjacent benign regions. In addition, more phospho-ERK1/2-positive cancer
cells existed in the peripheral region surrounded by the stroma than in the
central region of solid breast cancer nest. Thus, Mint3 in fibroblasts might be a
good target for cancer therapy by regulating cancer cell-stromal cell
communication.
PMID- 28504693
TI - Cyclin-dependent kinase 7 is a therapeutic target in high-grade glioma.
AB - High-grade glioma (HGG) is an incurable brain cancer. The transcriptomes of cells
within HGG tumors are highly heterogeneous. This renders the tumors unresponsive
or able to adapt to therapeutics targeted at single pathways, thereby causing
treatment failure. To overcome this, we focused on cyclin-dependent kinase 7
(CDK7), a ubiquitously expressed molecule involved in two major drivers of HGG
pathogenesis: cell cycle progression and RNA polymerase-II-based transcription.
We tested the activity of THZ1, an irreversible CDK7 inhibitor, on patient
derived primary HGG cell lines and ex vivo HGG patient tissue slices, using
proliferation assays, microarray analysis, high-resolution respirometry, cell
cycle analysis and in vivo tumor orthografts. The cellular processes affected by
CDK7 inhibition were analyzed by reverse transcriptase-quantitative PCR, western
blot, flow cytometry and immunofluorescence. THZ1 perturbed the transcriptome and
disabled CDK activation, leading to cell cycle arrest at G2 and DNA damage. THZ1
halted transcription of the nuclear-encoded mitochondrial ribosomal genes,
reducing mitochondrial translation and oxidative respiration. It also inhibited
the expression of receptor tyrosine kinases such as epidermal growth factor
receptor (EGFR) and platelet-derived growth factor receptor-alpha (PDGFR-alpha),
reducing signaling flux through the AKT, extracellular-signal-regulated kinase
1/2 (ERK1/2) and signal transducer and activator of transcription 3 (STAT3)
downstream pathways. Finally, THZ1 disrupted nucleolar, Cajal body and nuclear
speckle formation, resulting in reduced cytosolic translation and malfunction of
the spliceosome and thus leading to aberrant mRNA processing. These findings
indicate that CDK7 is crucial for gliomagenesis, validate CDK7 as a therapeutic
target and provide new insight into the cellular processes that are affected by
THZ1 and induce antitumor activity.
PMID- 28504694
TI - The prohibitin-repressive interaction with E2F1 is rapidly inhibited by androgen
signalling in prostate cancer cells.
AB - Prohibitin (PHB) is a tumour suppressor molecule with pleiotropic activities
across several cellular compartments including mitochondria, cell membrane and
the nucleus. PHB and the steroid-activated androgen receptor (AR) have an
interplay where AR downregulates PHB, and PHB represses AR. Additionally, their
cellular locations and chromatin interactions are in dynamic opposition. We
investigated the mechanisms of cell cycle inhibition by PHB and how this is
modulated by AR in prostate cancer. Using a prostate cancer cell line
overexpressing PHB, we analysed the gene expression changes associated with PHB
mediated cell cycle arrest. Over 1000 gene expression changes were found to be
significant and gene ontology analysis confirmed PHB-mediated repression of genes
essential for DNA replication and synthesis, for example, MCMs and TK1, via an
E2F1 regulated pathway-agreeing with its G1/S cell cycle arrest activity. PHB is
known to inhibit E2F1-mediated transcription, and the PHB:E2F1 interaction was
seen in LNCaP nuclear extracts, which was then reduced by androgen treatment.
Upon two-dimensional western blot analysis, the PHB protein itself showed
androgen-mediated charge differentiation (only in AR-positive cells), indicating
a potential dephosphorylation event. Kinexus phosphoprotein array analysis
indicated that Src kinase was the main interacting intracellular signalling hub
in androgen-treated LNCaP cells, and that Src inhibition could reduce this AR
mediated charge differentiation. PHB charge change may be associated with rapid
dissociation from chromatin and E2F1, allowing the cell cycle to proceed. The AR
and androgens may deactivate the repressive functions of PHB upon E2F1 leading to
cell cycle progression, and indicates a role for AR in DNA replication licensing.
PMID- 28504695
TI - Epigenetic pathway inhibitors represent potential drugs for treating pancreatic
and bronchial neuroendocrine tumors.
AB - Cancer is associated with alterations in epigenetic mechanisms such as histone
modifications and methylation of DNA, and inhibitors targeting epigenetic
mechanisms represent a novel class of anti-cancer drugs. Neuroendocrine tumors
(NETs) of the pancreas (PNETs) and bronchus (BNETs), which may have 5-year
survivals of <50% and as low as 5%, respectively, represent targets for such
drugs, as >40% of PNETs and ~35% of BNETs have mutations of the multiple
endocrine neoplasia type 1 (MEN1) gene, which encodes menin that modifies
histones by interacting with histone methyltransferases. We assessed 9 inhibitors
of epigenetic pathways, for their effects on proliferation, by CellTiter Blue
assay, and apoptosis, by CaspaseGlo assay, using 1 PNET and 2 BNET cell lines.
Two inhibitors, referred to as (+)-JQ1 (JQ1) and PFI-1, targeting the bromo and
extra terminal (BET) protein family which bind acetylated histone residues, were
most effective in decreasing proliferation (by 40-85%, P<0.001) and increasing
apoptosis (by 2-3.6 fold, P<0.001) in all 3 NET cell lines. The anti
proliferative effects of JQ1 and PFI-1 remained present for at least 48 hours
after removal of the compound. JQ1, but not PFI-1, had cell cycle effects,
assessed by propidium iodide staining and flow cytometry, resulting in increased
and decreased proportions of NET cells in G1, and S and G2 phases, respectively.
RNA Sequencing analysis revealed that these JQ1 effects were associated with
increased histone 2B expression, and likely mediated through altered activity of
bromodomain-containing (Brd) proteins. Assessment of JQ1 in vivo, using a
pancreatic beta cell-specific conditional Men1 knockout mouse model that develops
PNETs, revealed that JQ1 significantly reduced proliferation (by ~50%, P<0.0005),
assessed by bromodeoxyuridine incorporation, and increased apoptosis (by ~3 fold,
P<0.0005), assessed by terminal deoxynucleotidyl transferase dUTP nick end
labelling, of PNETs. Thus, our studies demonstrate that BET protein inhibitors
may provide new treatments for NETs.
PMID- 28504696
TI - 5-Formylcytosine does not change the global structure of DNA.
AB - The mechanism by which the recently identified DNA modification 5-formylcytosine
(fC) is recognized by epigenetic writer and reader proteins is not known.
Recently, an unusual DNA structure, F-DNA, has been proposed as the basis for
enzyme recognition of clusters of fC. We used NMR and X-ray crystallography to
compare several modified DNA duplexes with unmodified analogs and found that in
the crystal state the duplexes all belong to the A family, whereas in solution
they are all members of the B family. We found that, contrary to previous
findings, fC does not significantly affect the structure of DNA, although there
are modest local differences at the modification sites. Hence, global
conformation changes are unlikely to account for the recognition of this modified
base, and our structural data favor a mechanism that operates at base-pair
resolution for the recognition of fC by epigenome-modifying enzymes.
PMID- 28504699
TI - Expansion of the redox-sensitive proteome coincides with the plastid
endosymbiosis.
AB - The redox-sensitive proteome (RSP) consists of protein thiols that undergo redox
reactions, playing an important role in coordinating cellular processes. Here, we
applied a large-scale phylogenomic reconstruction approach in the model diatom
Phaeodactylum tricornutum to map the evolutionary origins of the eukaryotic RSP.
The majority of P. tricornutum redox-sensitive cysteines (76%) is specific to
eukaryotes, yet these are encoded in genes that are mostly of a prokaryotic
origin (57%). Furthermore, we find a threefold enrichment in redox-sensitive
cysteines in genes that were gained by endosymbiotic gene transfer during the
primary plastid acquisition. The secondary endosymbiosis event coincides with
frequent introduction of reactive cysteines into existing proteins. While the
plastid acquisition imposed an increase in the production of reactive oxygen
species, our results suggest that it was accompanied by significant expansion of
the RSP, providing redox regulatory networks the ability to cope with fluctuating
environmental conditions.
PMID- 28504697
TI - The transcriptional coactivator TAZ regulates reciprocal differentiation of TH17
cells and Treg cells.
AB - An imbalance in the lineages of immunosuppressive regulatory T cells (Treg cells)
and the inflammatory TH17 subset of helper T cells leads to the development of
autoimmune and/or inflammatory disease. Here we found that TAZ, a coactivator of
TEAD transcription factors of Hippo signaling, was expressed under TH17 cell
inducing conditions and was required for TH17 differentiation and TH17 cell
mediated inflammatory diseases. TAZ was a critical co-activator of the TH17
defining transcription factor RORgammat. In addition, TAZ attenuated Treg cell
development by decreasing acetylation of the Treg cell master regulator Foxp3
mediated by the histone acetyltransferase Tip60, which targeted Foxp3 for
proteasomal degradation. In contrast, under Treg cell-skewing conditions, TEAD1
expression and sequestration of TAZ from the transcription factors RORgammat and
Foxp3 promoted Treg cell differentiation. Furthermore, deficiency in TAZ or
overexpression of TEAD1 induced Treg cell differentiation, whereas expression of
a transgene encoding TAZ or activation of TAZ directed TH17 cell differentiation.
Our results demonstrate a pivotal role for TAZ in regulating the differentiation
of Treg cells and TH17 cells.
PMID- 28504698
TI - Dendritic cells enter lymph vessels by hyaluronan-mediated docking to the
endothelial receptor LYVE-1.
AB - Trafficking of tissue dendritic cells (DCs) via lymph is critical for the
generation of cellular immune responses in draining lymph nodes (LNs). In the
current study we found that DCs docked to the basolateral surface of lymphatic
vessels and transited to the lumen through hyaluronan-mediated interactions with
the lymph-specific endothelial receptor LYVE-1, in dynamic transmigratory-cup
like structures. Furthermore, we show that targeted deletion of the gene Lyve1,
antibody blockade or depletion of the DC hyaluronan coat not only delayed
lymphatic trafficking of dermal DCs but also blunted their capacity to prime CD8+
T cell responses in skin-draining LNs. Our findings uncovered a previously
unknown function for LYVE-1 and show that transit through the lymphatic network
is initiated by the recognition of leukocyte-derived hyaluronan.
PMID- 28504700
TI - Lineage-specific functions of TET1 in the postimplantation mouse embryo.
AB - The mammalian TET enzymes catalyze DNA demethylation. While they have been
intensely studied as major epigenetic regulators, little is known about their
physiological roles and the extent of functional redundancy following embryo
implantation. Here we define non-redundant roles for TET1 at an early
postimplantation stage of the mouse embryo, when its paralogs Tet2 and Tet3 are
not detectably expressed. TET1 regulates numerous genes defining differentiation
programs in the epiblast and extraembryonic ectoderm. In epiblast cells, TET1
demethylates gene promoters via hydroxymethylation and maintains telomere
stability. Surprisingly, TET1 represses a majority of epiblast target genes
independently of methylation changes, in part through regulation of the gene
encoding the transcriptional repressor JMJD8. Dysregulated gene expression in the
absence of TET1 causes embryonic defects, which are partially penetrant in an
inbred strain but fully lethal in non-inbred mice. Collectively, our study
highlights an interplay between the catalytic and non-catalytic activities of
TET1 that is essential for normal development.
PMID- 28504701
TI - Paused RNA polymerase II inhibits new transcriptional initiation.
AB - RNA polymerase II (Pol II) pauses downstream of the transcription initiation site
before beginning productive elongation. This pause is a key component of metazoan
gene expression regulation. Some promoters have a strong disposition for Pol II
pausing and often mediate faster, more synchronous changes in expression. This
requires multiple rounds of transcription and thus cannot rely solely on pause
release. However, it is unclear how pausing affects the initiation of new
transcripts during consecutive rounds of transcription. Using our recently
developed ChIP-nexus method, we find that Pol II pausing inhibits new initiation.
We propose that paused Pol II helps prevent new initiation between transcription
bursts, which may reduce noise.
PMID- 28504704
TI - Glyphosate resistance: Of superweeds and survivors.
PMID- 28504702
TI - PGBD5 promotes site-specific oncogenic mutations in human tumors.
AB - Genomic rearrangements are a hallmark of human cancers. Here, we identify the
piggyBac transposable element derived 5 (PGBD5) gene as encoding an active DNA
transposase expressed in the majority of childhood solid tumors, including lethal
rhabdoid tumors. Using assembly-based whole-genome DNA sequencing, we found
previously undefined genomic rearrangements in human rhabdoid tumors. These
rearrangements involved PGBD5-specific signal (PSS) sequences at their
breakpoints and recurrently inactivated tumor-suppressor genes. PGBD5 was
physically associated with genomic PSS sequences that were also sufficient to
mediate PGBD5-induced DNA rearrangements in rhabdoid tumor cells. Ectopic
expression of PGBD5 in primary immortalized human cells was sufficient to promote
cell transformation in vivo. This activity required specific catalytic residues
in the PGBD5 transposase domain as well as end-joining DNA repair and induced
structural rearrangements with PSS breakpoints. These results define PGBD5 as an
oncogenic mutator and provide a plausible mechanism for site-specific DNA
rearrangements in childhood and adult solid tumors.
PMID- 28504705
TI - Wounding induces dedifferentiation of epidermal Gata6+ cells and acquisition of
stem cell properties.
AB - The epidermis is maintained by multiple stem cell populations whose progeny
differentiate along diverse, and spatially distinct, lineages. Here we show that
the transcription factor Gata6 controls the identity of the previously
uncharacterized sebaceous duct (SD) lineage and identify the Gata6 downstream
transcription factor network that specifies a lineage switch between sebocytes
and SD cells. During wound healing differentiated Gata6+ cells migrate from the
SD into the interfollicular epidermis and dedifferentiate, acquiring the ability
to undergo long-term self-renewal and differentiate into a much wider range of
epidermal lineages than in undamaged tissue. Our data not only demonstrate that
the structural and functional complexity of the junctional zone is regulated by
Gata6, but also reveal that dedifferentiation is a previously unrecognized
property of post-mitotic, terminally differentiated cells that have lost contact
with the basement membrane. This resolves the long-standing debate about the
contribution of terminally differentiated cells to epidermal wound repair.
PMID- 28504708
TI - Receptor oligomerization guides pathway choice between proteasomal and autophagic
degradation.
AB - Abnormal or aggregated proteins have a strong cytotoxic potential and are
causative for human disorders such as Alzheimer's, Parkinson's, Huntington's
disease and amyotrophic lateral sclerosis. If not restored by molecular
chaperones, abnormal proteins are typically degraded by proteasomes or eliminated
by selective autophagy. The discovery that both pathways are initiated by
substrate ubiquitylation but utilize different ubiquitin receptors incited a
debate over how pathway choice is achieved. Here, we demonstrate in yeast that
pathway choice is made after substrate ubiquitylation by competing ubiquitin
receptors harbouring either proteasome- or autophagy-related protein 8 (Atg8/LC3)
binding modules. Proteasome pathway receptors bind ubiquitin moieties more
efficiently, but autophagy receptors gain the upper hand following substrate
aggregation and receptor bundling. Indeed, by using sets of modular artificial
receptors harbouring identical ubiquitin-binding modules we found that
proteasome/autophagy pathway choice is independent of the ubiquitin-binding
properties of the receptors but largely determined by their oligomerization
potentials. Our work thus suggests that proteasomal degradation and selective
autophagy are two branches of an adaptive protein quality control pathway, which
uses substrate ubiquitylation as a shared degradation signal.
PMID- 28504706
TI - The mitochondrial respiratory chain is essential for haematopoietic stem cell
function.
AB - Adult and fetal haematopoietic stem cells (HSCs) display a glycolytic phenotype,
which is required for maintenance of stemness; however, whether mitochondrial
respiration is required to maintain HSC function is not known. Here we report
that loss of the mitochondrial complex III subunit Rieske iron-sulfur protein
(RISP) in fetal mouse HSCs allows them to proliferate but impairs their
differentiation, resulting in anaemia and prenatal death. RISP-null fetal HSCs
displayed impaired respiration resulting in a decreased NAD+/NADH ratio. RISP
null fetal HSCs and progenitors exhibited an increase in both DNA and histone
methylation associated with increases in 2-hydroxyglutarate (2HG), a metabolite
known to inhibit DNA and histone demethylases. RISP inactivation in adult HSCs
also impaired respiration resulting in loss of quiescence concomitant with severe
pancytopenia and lethality. Thus, respiration is dispensable for adult or fetal
HSC proliferation, but essential for fetal HSC differentiation and maintenance of
adult HSC quiescence.
PMID- 28504703
TI - Polygenic transmission disequilibrium confirms that common and rare variation act
additively to create risk for autism spectrum disorders.
AB - Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo
variation. We aimed to clarify the influence of polygenic risk for ASD and to
identify subgroups of ASD cases, including those with strongly acting de novo
variants, in which polygenic risk is relevant. Using a novel approach called the
polygenic transmission disequilibrium test and data from 6,454 families with a
child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater
educational attainment is over-transmitted to children with ASD. These findings
hold independent of proband IQ. We find that polygenic variation contributes
additively to risk in ASD cases who carry a strongly acting de novo variant.
Lastly, we show that elements of polygenic risk are independent and differ in
their relationship with phenotype. These results confirm that the genetic
influences on ASD are additive and suggest that they create risk through at least
partially distinct etiologic pathways.
PMID- 28504707
TI - Regulation of mitochondrial biogenesis in erythropoiesis by mTORC1-mediated
protein translation.
AB - Advances in genomic profiling present new challenges of explaining how changes in
DNA and RNA are translated into proteins linking genotype to phenotype. Here we
compare the genome-scale proteomic and transcriptomic changes in human primary
haematopoietic stem/progenitor cells and erythroid progenitors, and uncover
pathways related to mitochondrial biogenesis enhanced through post
transcriptional regulation. Mitochondrial factors including TFAM and PHB2 are
selectively regulated through protein translation during erythroid specification.
Depletion of TFAM in erythroid cells alters intracellular metabolism, leading to
elevated histone acetylation, deregulated gene expression, and defective
mitochondria and erythropoiesis. Mechanistically, mTORC1 signalling is enhanced
to promote translation of mitochondria-associated transcripts through TOP-like
motifs. Genetic and pharmacological perturbation of mitochondria or mTORC1
specifically impairs erythropoiesis in vitro and in vivo. Our studies support a
mechanism for post-transcriptional control of erythroid mitochondria and may have
direct relevance to haematologic defects associated with mitochondrial diseases
and ageing.
PMID- 28504709
TI - Food security is related to adult type 2 diabetes control over time in a United
States safety net primary care clinic population.
AB - BACKGROUND/OBJECTIVES: Successful Type 2 diabetes management requires adopting a
high nutrient-density diet made up of food items that both meet dietary needs and
preferences and can be feasibly obtained on a regular basis. However, access to
affordable, nutrient-dense foods often is lacking in poorer neighbourhoods.
Therefore, low food security should directly impair glucose control, even when
patients have full access to and utilize comprehensive medical management. The
present study sought to determine whether food security is related longitudinally
to glucose control, over-and-above ongoing medication management, among Type 2
diabetes patients receiving comprehensive care at a Midwestern multi-site
federally qualified health centre (FQHC). SUBJECTS/METHODS: In this longitudinal
observational study, we completed a baseline assessment of patients' food
security (using the US Household Food Security Module), demographics (via Census
items), and diabetes history/management (using a structured clinical encounter
form) when patients began receiving diabetes care at the health centre. We then
recorded those patients' A1C levels several times during a 24-month follow-up
period. Three hundred and ninety-nine patients (56% with low food security) had a
baseline A1c measurement; a subsample of 336 (median age=52 years; 56% female;
60% Hispanic, 27% African American, and 9% White) also had at least one follow-up
A1c measurement. RESULTS: Patients with lower (vs higher) food security were more
likely to be on insulin and have higher A1c levels at baseline. Moreover, the
disparity in glucose control by food security status persisted throughout the
next 2 years. CONCLUSIONS: Although results were based on one multi-site FQHC,
potentially limiting their generalizability, they seem to suggest that among Type
2 diabetes patients, low food security directly impairs glucose control-even when
patients receive full access to comprehensive medical management-thereby
increasing their long-term risks of high morbidity, early mortality, and high
health-care utilization and cost.
PMID- 28504710
TI - A1 beta-casein milk protein and other environmental pre-disposing factors for
type 1 diabetes.
AB - Globally type 1 diabetes incidence is increasing. It is widely accepted that the
pathophysiology of type 1 diabetes is influenced by environmental factors in
people with specific human leukocyte antigen haplotypes. We propose that a
complex interplay between dietary triggers, permissive gut factors and
potentially other influencing factors underpins disease progression. We present
evidence that A1 beta-casein cows' milk protein is a primary causal trigger of
type 1 diabetes in individuals with genetic risk factors. Permissive gut factors
(for example, aberrant mucosal immunity), intervene by impacting the gut's
environment and the mucosal barrier. Various influencing factors (for example,
breastfeeding duration, exposure to other dietary triggers and vitamin D) modify
the impact of triggers and permissive gut factors on disease. The power of the
dominant trigger and permissive gut factors on disease is influenced by timing,
magnitude and/or duration of exposure. Within this framework, removal of a
dominant dietary trigger may profoundly affect type 1 diabetes incidence. We
present epidemiological, animal-based, in vitro and theoretical evidence for A1
beta-casein and its beta-casomorphin-7 derivative as dominant causal triggers of
type 1 diabetes. The effects of ordinary milk containing A1 and A2 beta-casein
and milk containing only the A2 beta-casein warrant comparison in prospective
trials.
PMID- 28504711
TI - The stabilizing effect of an oligomeric proanthocyanidin on red blood cell
membrane structure of poorly controlled Type II diabetes.
AB - Type II diabetes (T2D) is a pandemic characterized by pathological circulating
inflammatory markers, high-glucose levels and oxidative stress. The hematological
system is especially vulnerable to these aberrant circulating molecules, and
erythrocytes (RBCs) show aberrant rheology properties, owing to the direct
contact with these molecules. Pathological levels of circulating inflammatory
markers in T2D therefore have a direct effect on the molecular and cellular
structure of RBCs. Previous research has suggested that antioxidants may reduce
oxidative stress that results from the pathological inflammatory markers.
Particularly, polyphenol antioxidants like oligomeric proanthocyanidins (OPCs)
may act as a hydroxyl mopping agent, and may have a positive effect on the
deformability and membrane protein structure of RBCs from T2D. In this paper, we
look at the effect of one such agent, Pinus massoniana bark extract (standardized
to 95% oligomeric proanthicyanidins), on the RBC membrane structures and RBC
shape changes of T2D, after laboratory exposure at physiological levels. Our
methods of choice were atomic force microscopy and scanning electron microscopy
to study RBC elasticity and ultrastructure. Results showed that in our hands,
this OPC could change both the eryptotic nature of the RBCs, as viewed with
scanning electron microscopy, as well as the elasticity. We found a significant
difference in variation between the elasticity measurement values between the
RBCs before and after OPC exposure (P-value <0.0001). In conclusion, the data
from both these techniques therefore suggest that OPC usage might contribute to
the improvement of RBC functioning.
PMID- 28504712
TI - Flavonoid intake is inversely associated with obesity and C-reactive protein, a
marker for inflammation, in US adults.
AB - Recent studies have demonstrated the importance of flavonoid intake and disease
risk, however the association between flavonoid intake and obesity has not been
evaluated in a nationally representative sample of US adults. The objective of
the study was to evaluate the association between flavonoid consumption and
established risk factors for obesity and obesity-related inflammation. Data from
a nationally representative sample of 9551 adults who participated in the 2005
2008 National Health and Nutrition Examination Survey (NHANES) were analyzed.
Flavonoid consumption was inversely associated with obesity in both men and women
in multivariate models. Adults in the highest quartile of flavonoid intake had
significantly lower body mass index and waist circumference than those in the
lowest quartile of flavonoid intake (P<0.03 and P<0.04, respectively), and
flavonoid intake was inversely related to C-reactive protein levels in women (p
trend, 0.01). These findings support a growing body of laboratory evidence that
flavonoid consumption may be beneficial for disease prevention.
PMID- 28504714
TI - Cytoplasmic translocation of MTA1 coregulator promotes de-repression of SGK1
transcription in hypoxic cancer cells.
AB - Chromatin remodeling factor metastatic tumor protein 1 (MTA1), one of the most
upregulated oncogene in human cancer, has an important role in gene expression,
cell survival and promoting hypoxic response. Successful cancer progression is
dependent on the ability of cells to utilize its survival pathways for adapting
to hypoxic microenvironment. Although MTA1 is a stress-responsive gene, but
whether hypoxia modulates its function and its role in engaging other core stress
responsive survival pathway(s) remains unknown. Here we have discovered that MTA1
is a novel corepressor of serum and glucocorticoid-inducible kinase 1 (SGK1).
Surprisingly, this regulatory corepressive function of MTA1 is lost under
hypoxia, allowing upregulation of SGK1 expression and engaging the MTA1-SGK1 axis
for the benefit of the cell survival. The underlying mechanism of the noticed
stimulation of SGK1 expression by hypoxia includes de-repression of SGK1
transcription because of hypoxia-triggered nucleus-to-cytoplasmic translocation
of MTA1. In addition, the newly recognized cytoplasmic translocation of MTA1 was
dependent on the chaperoning function of heat shock protein 90 (HSP90) and co
accompanied by the formation of MTA1, HSP90 and HIF1alpha complex under hypoxic
condition but not under normoxic condition. Hypoxia-triggered redistribution of
MTA1, SGK1 upregulation and cell survival functions were compromised by a
pharmacological SGK1 inhibitor. In summary, for the first time, we report MTA1
regulation of SGK1 expression, hypoxia-dependent MTA1 translocation to the
cytoplasm and de-repression of SGK1 transcription. These findings illustrate how
cancer cells utilize a chromatin remodeling factor to engage a core survival
pathway to support its cancerous phenotypes, and reveal new facets of MTA1-SGK1
axis by a physiologic signal in cancer progression.
PMID- 28504713
TI - Elevated PTTG and PBF predicts poor patient outcome and modulates DNA damage
response genes in thyroid cancer.
AB - The proto-oncogene PTTG and its binding partner PBF have been widely studied in
multiple cancer types, particularly thyroid and colorectal, but their combined
role in tumourigenesis is uncharacterised. Here, we show for the first time that
together PTTG and PBF significantly modulate DNA damage response (DDR) genes,
including p53 target genes, required to maintain genomic integrity in thyroid
cells. Critically, DDR genes were extensively repressed in primary thyrocytes
from a bitransgenic murine model (Bi-Tg) of thyroid-specific PBF and PTTG
overexpression. Irradiation exposure to amplify p53 levels further induced
significant repression of DDR genes in Bi-Tg thyrocytes (P=2.4 * 10-4) compared
with either PBF- (P=1.5 * 10-3) or PTTG-expressing thyrocytes (P=NS). Consistent
with this, genetic instability was greatest in Bi-Tg thyrocytes with a mean
genetic instability (GI) index of 35.8+/-2.6%, as well as significant induction
of gross chromosomal aberrations in thyroidal TPC-1 cells following
overexpression of PBF and PTTG. We extended our findings to human thyroid cancer
using TCGA data sets (n=322) and found striking correlations with PBF and PTTG
expression in well-characterised DDR gene panel RNA-seq data. In addition,
genetic associations and transient transfection identified PBF as a downstream
target of the receptor tyrosine kinase-BRAF signalling pathway, emphasising a
role for PBF as a novel component in a pathway well described to drive neoplastic
growth. We also showed that overall survival (P=1.91 * 10-5) and disease-free
survival (P=4.9 * 10-5) was poorer for TCGA patients with elevated tumoural
PBF/PTTG expression and mutationally activated BRAF. Together our findings
indicate that PBF and PTTG have a critical role in promoting thyroid cancer that
is predictive of poorer patient outcome.
PMID- 28504715
TI - Human DBR1 modulates the recycling of snRNPs to affect alternative RNA splicing
and contributes to the suppression of cancer development.
AB - The contribution of RNA processing to tumorigenesis is understudied. Here, we
report that the human RNA debranching enzyme (hDBR1), when inappropriately
regulated, induces oncogenesis by causing RNA processing defects, for example,
splicing defects. We found that wild-type p53 and hypoxia-inducible factor 1 co
regulate hDBR1 expression, and insufficient hDBR1 leads to a higher rate of exon
skipping. Transcriptomic sequencing confirmed the effect of hDBR1 on RNA
splicing, and metabolite profiling supported the observation that neoplasm is
triggered by a decrease in hDBR1 expression both in vitro and in vivo. Most
importantly, when modulating the expression of hDBR1, which was found to be
generally low in malignant human tissues, higher expression of hDBR1 only
affected exon-skipping activity in malignant cells. Together, our findings
demonstrate previously unrecognized regulation and functions of hDBR1, with
immediate clinical implications regarding the regulation of hDBR1 as an effective
strategy for combating human cancer.
PMID- 28504716
TI - VEGFA links self-renewal and metastasis by inducing Sox2 to repress miR-452,
driving Slug.
AB - Cancer stem cells (CSC) appear to have increased metastatic potential, but
mechanisms underlying this are poorly defined. Here we show that VEGFA induction
of Sox2 promotes EMT and tumor metastasis. In breast lines and primary cancer
culture, VEGFA rapidly upregulates SOX2 expression, leading to SNAI2 induction,
EMT, increased invasion and metastasis. We show Sox2 downregulates miR-452, which
acts as a novel metastasis suppressor to directly target the SNAI2 3'
untranslated region (3'-UTR). VEGFA stimulates Sox2- and Slug-dependent cell
invasion. VEGFA increases lung metastasis in vivo, and this is abrogated by miR
452 overexpression. Furthermore, SNAI2 transduction rescues metastasis
suppression by miR-452. Thus, in addition to its angiogenic action, VEGFA
upregulates Sox2 to drive stem cell expansion, together with miR-452 loss and
Slug upregulation, providing a novel mechanism whereby cancer stem cells acquire
metastatic potential. Prior work showed EMT transcription factor overexpression
upregulates CSC. Present work indicates that stemness and metastasis are a two
way street: Sox2, a major mediator of CSC self-renewal, also governs the
metastatic process.
PMID- 28504717
TI - Fibulin-3 promotes muscle-invasive bladder cancer.
AB - Urothelial carcinoma is the most common type of bladder cancer and can be
categorized as either non-muscle-invasive (Ta-T1) or muscle-invasive (?T2). The
majority of bladder cancers are non-muscle-invasive at presentation; however, the
recurrence rate for these tumors is high and a subset can progress to T2. In this
study, we aimed to identify genes differentially expressed between T1 vs T2
bladder cancer to identify key regulators of bladder cancer progression and/or
invasion. We performed RNA-Seq on T1 and T2 bladder cancer tissues and used
publicly available bladder cancer profiling studies to prioritize differentially
expressed genes for validation and functional assessment. This integrative
approach nominated an extracellular matrix glycoprotein, fibulin-3 (FBLN3, also
known as EFEMP1), as being highly expressed in T2 vs T1 bladder cancer and
aggressive vs indolent disease. We confirmed the overexpression of fibulin-3 in
?T2 vs non-muscle-invasive bladder cancer (NMIBC) by quantitative reverse
transcriptase-PCR. Consistent with these findings, fibulin-3 expression level
correlated with the invasive ability of several bladder cancer cell lines and
modulation of fibulin-3 expression directly affected invasion. Fibulin-3
knockdown in bladder cancer cells decreased the incidence of MIBCs in a murine
orthotopic bladder cancer model and decreased the expression of insulin-like
growth factor-binding protein-5 (IGFBP5). Restoring IGFBP5 in these cells rescued
their invasive and migratory potential. These results indicate that fibulin-3
serves as a pro-invasive factor in bladder cancer, which may be mediated through
modulation of IGFBP5 expression. This also suggests fibulin-3 and IGFBP5 may have
potential as biomarkers of aggressive bladder cancer or therapeutic targets.
PMID- 28504719
TI - Novel MYC-driven medulloblastoma models from multiple embryonic cerebellar cells.
AB - Group3 medulloblastoma (MBG3) that predominantly occur in young children are
usually associated with MYC amplification and/or overexpression, frequent
metastasis and a dismal prognosis. Physiologically relevant MBG3 models are
currently lacking, making inferences related to their cellular origin thus far
limited. Using in utero electroporation, we here report that MBG3 mouse models
can be developed in situ from different multipotent embryonic cerebellar
progenitor cells via conditional expression of Myc and loss of Trp53 function in
several Cre driver mouse lines. The Blbp-Cre driver that targets embryonic neural
progenitors induced tumors exhibiting a large-cell/anaplastic histopathology
adjacent to the fourth ventricle, recapitulating human MBG3. Enforced co
expression of luciferase together with Myc and a dominant-negative form of Trp53
revealed that GABAergic neuronal progenitors as well as cerebellar granule cells
give rise to MBG3 with their distinct growth kinetics. Cross-species gene
expression analysis revealed that these novel MBG3 models shared molecular
characteristics with human MBG3, irrespective of their cellular origin. We here
developed MBG3 mouse models in their physiological environment and we show that
oncogenic insults drive this MB subgroup in different cerebellar lineages rather
than in a specific cell of origin.
PMID- 28504718
TI - A tumor suppressor role for C/EBPalpha in solid tumors: more than fat and blood.
AB - The transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha) plays
a critical role during embryogenesis and is thereafter required for homeostatic
glucose metabolism, adipogenesis and myeloid development. Its ability to regulate
the expression of lineage-specific genes and induce growth arrest contributes to
the terminal differentiation of several cell types, including hepatocytes,
adipocytes and granulocytes. CEBPA loss of-function mutations contribute to the
development of ~10% of acute myeloid leukemia (AML), stablishing a tumor
suppressor role for C/EBPalpha. Deregulation of C/EBPalpha expression has also
been reported in a variety of additional human neoplasias, including liver,
breast and lung cancer. However, functional CEBPA mutations have not been found
in solid tumors, suggesting that abrogation of C/EBPalpha function in non
hematopoietic tissues is regulated by alternative mechanisms. Here we review the
function of C/EBPalpha in solid tumors and focus on the molecular mechanisms
underlying its tumor suppressive role.
PMID- 28504720
TI - A clinical drug library screen identifies clobetasol propionate as an NRF2
inhibitor with potential therapeutic efficacy in KEAP1 mutant lung cancer.
AB - The Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor E2-related factor
2 (NRF2)pathway has a central role in cellular antioxidant defense. NRF2
activation due to KEAP1 or NRF2 mutations occurs frequently in many cancers,
suggesting that NRF2 inhibition could be a promising therapeutic strategy.
However, no potent NRF2 inhibitors are clinically available to date. To develop
potent NRF2 inhibitors for therapeutic purpose, we screened ~4000 clinical
compounds and determined clobetasol propionate (CP) as the most potent NRF2
inhibitor. Mechanistically, CP prevented nuclear accumulation and promoted beta
TrCP-dependent degradation of NRF2 in a glucocorticoid receptor- and a glycogen
synthase kinase 3 (GSK3)-dependent manner. As a result, CP induced oxidative
stress and strongly suppressed the anchorage-independent growth of tumors with
KEAP1 mutation, but not with the wild-type KEAP1. Further, CP alone or in
combination with rapamycin strongly inhibited the in vitro and in vivo growth of
tumors harboring mutations in KEAP1 or both KEAP1 and LKB1 that are frequently
observed in lung cancer. Thus, CP could be a repurposed therapeutic agent for
cancers with high NRF2 activity. We also proposed that the use CP and rapamycin
in combination could be a potential therapeutic strategy for tumors harboring
both KEAP1 and LKB1 mutations.
PMID- 28504721
TI - Tumour exosomes from cells harbouring PTPRZ1-MET fusion contribute to a malignant
phenotype and temozolomide chemoresistance in glioblastoma.
AB - Exosomes are carriers of pro-tumorigenic factors that participate in glioblastoma
(GBM) progression, and many fusion genes are strong driver mutations in neoplasia
and are involved in tumorigenesis. However, the ability of fusion genes to be
transduced by exosomes is unknown. We characterized exosomes from GBM cells
harbouring and not harbouring PTPRZ1-MET fusion (ZM fusion). We also determined
the effect of the exosomes from ZM fusion cells (ZM exosomes) on pro-oncogenic
secretions and showed that ZM exosomes are internalized by the recipient cells.
In addition, we studied the effect of ZM exosome-mediated intercellular
communication in the GBM microenvironment. MET proto-oncogene expression was
higher in ZM exosomes. Moreover, phosphorylated MET was detected only in ZM
exosomes and not in exosomes released by non-ZM fusion GBM cells. ZM exosomes
transferred to non-ZM fusion GBM cells and normal human astrocytes altered gene
expression and induced epithelial-mesenchymal transition. The uptake of ZM
exosomes also induced an exosome-dependent phenotype defined by GBM cell
migration and invasion, neurosphere growth and angiogenesis. In addition, ZM
exosomes conferred temozolomide resistance to the GBM cells, and exosome-derived
ZM fusion network proteins targeted multiple pro-oncogenic effectors in recipient
cells within the GBM microenvironment. Our findings show that exosomes mediate
the aggressive character of GBM and demonstrate the role of ZM fusion in the
exacerbation of this effect. These findings have possible implications for the
foundation of gene fusion-based therapy for managing GBM.
PMID- 28504722
TI - Thyroid hormone protects hepatocytes from HBx-induced carcinogenesis by enhancing
mitochondrial turnover.
AB - Infection by hepatitis B virus (HBV) accounts for 50-80% of hepatocellular
carcinoma (HCC) development worldwide, in which the HBV-encoded X protein (HBx)
has critical role in the induction of carcinogenesis. Several studies have shown
that thyroid hormone (TH) suppresses HCC development and protects hepatocytes
from HBx-induced damage, thus it is of interest to examine whether TH can protect
hepatocytes from HBx-induced carcinogenesis. By treating HBx- transgenic mice
with or without TH, we confirmed the protective effects of TH on HBx-induced
hepatocarcinogenesis, which was achieved via reduction of reactive oxygen species
(ROS) inflicted DNA damage. We further found that TH induced biogenesis of
mitochondria (MITO) and autophagy of HBx-targeted MITO simultaneously,
consequently leading to suppression of HBx-promoted ROS and carcinogenesis. Using
microarray data analysis, this protective effect of TH was found to be mediated
via activation of PTEN-induced kinase 1 (PINK1) in hepatocytes. PINK1, in turn,
activated and recruited Parkin, an E3 ligase, to ubiquitinate MITO-associated HBx
protein and trigger selective mitophagy. The pathological significance of the
TH/PINK1 pathway in liver protection was confirmed by the concomitant decrease in
expression of both TR and PINK1 in matched HCC tumor tissues and negatively
correlated with aggressive progression of cancer and poor prognosis. Our data
indicate that TH/PINK1/Parkin pathway has a critical role in protecting
hepatocytes from HBx-induced carcinogenesis. Notably, several liver-targeting
therapeutic derivatives of TH facilitating prevention or therapy of steatosis
have been identified. Furthermore, our proof-of-concept experiments suggest that
application of T3 constitutes an effective novel therapeutic or preventive option
for HCC. Thus, the utilization of the agonists of TRs could be the meaningful
strategy in liver relative diseases, ranging from simple hepatic steatosis to
HCC.
PMID- 28504723
TI - CX3CR1+ monocytes modulate learning and learning-dependent dendritic spine
remodeling via TNF-alpha.
AB - Impaired learning and cognitive function often occurs during systemic infection
or inflammation. Although activation of the innate immune system has been linked
to the behavioral and cognitive effects that are associated with infection, the
underlying mechanisms remain poorly understood. Here we mimicked viral immune
activation with poly(I:C), a synthetic analog of double-stranded RNA, and
longitudinally imaged postsynaptic dendritic spines of layer V pyramidal neurons
in the mouse primary motor cortex using two-photon microscopy. We found that
peripheral immune activation caused dendritic spine loss, impairments in learning
dependent dendritic spine formation and deficits in multiple learning tasks in
mice. These observed synaptic alterations in the cortex were mediated by
peripheral-monocyte-derived cells and did not require microglial function in the
central nervous system. Furthermore, activation of CX3CR1highLy6Clow monocytes
impaired motor learning and learning-related dendritic spine plasticity through
tumor necrosis factor (TNF)-alpha-dependent mechanisms. Taken together, our
results highlight CX3CR1high monocytes and TNF-alpha as potential therapeutic
targets for preventing infection-induced cognitive dysfunction.
PMID- 28504726
TI - Multiple wavelength stabilization on a single optical cavity using the offset
sideband locking technique.
AB - We implemented a compact, robust, and stable device for simultaneous frequency
stabilization of lasers with different wavelengths used for the cooling and
trapping of Yb atoms in an optical lattice clock. The lasers at 399, 556, and 759
nm are locked to a single ultra-stable cavity using the offset sideband locking
technique, a modified version of the Pound-Drever-Hall method. For the most
demanding stabilization here, the 556 nm laser, this system exhibits a 300 Hz
linewidth for an integration time of 80 ms. We observed a long-term drift of less
than 20 kHz per day at 759 nm that is suitable for operating the lattice laser
with a light shift uncertainty below 1*10-18. We successfully tested
the system for operating the clock during a typical working day by simultaneously
locking the three lasers to the cavity.
PMID- 28504727
TI - Reduced-symmetry LMA rod-type fiber for enhanced higher-order mode
delocalization.
AB - We present a novel design of a micro-structured large-pitch, large-mode-area
(LMA) asymmetric rod-type fiber. By reducing the cladding symmetry through six
high-refractive index germanium-doped silica inclusions, the fiber features
strong higher-order mode (HOM) delocalization, leading to a potentially enhanced
preferential gain for the fundamental mode in active fibers. In addition, high
resolution spatially and spectrally (S2) resolved mode analysis
measurements confirm HOM contributions below 1% and LP1m-like HOM
contributions below the detection limit. This proposed fiber design enables
single-mode operation, with near-diffraction-limited beam quality of
M2=1.3 and an effective mode area of 2560 MUm2 at 1064 nm.
This design opens new insights into improving the threshold-like onset of modal
instabilities in high-power fiber lasers and fiber amplifiers by efficiently
suppressing LP11 modes.
PMID- 28504728
TI - Scalable Fourier transform system for instantly structured illumination in
lithography.
AB - We report the development of a unique scalable Fourier transform 4-f system for
instantly structured illumination in lithography. In the 4-f system, coupled with
a 1-D grating and a phase retarder, the +/-1st order of diffracted light from the
grating serve as coherent incident sources for creating interference patterns on
the image plane. By adjusting the grating and the phase retarder, the
interference fringes with consecutive frequencies, as well as their orientations
and phase shifts, can be generated instantly within a constant interference area.
We demonstrate that by adapting this scalable Fourier transform system into
lithography, the pixelated nano-fringe arrays with arbitrary frequencies and
orientations can be dynamically produced in the photoresist with high variation
resolution, suggesting its promising application for large-area functional
materials based on space-variant nanostructures in lithography.
PMID- 28504725
TI - Metformin ameliorates core deficits in a mouse model of fragile X syndrome.
AB - Fragile X syndrome (FXS) is the leading monogenic cause of autism spectrum
disorders (ASD). Trinucleotide repeat expansions in FMR1 abolish FMRP expression,
leading to hyperactivation of ERK and mTOR signaling upstream of mRNA
translation. Here we show that metformin, the most widely used drug for type 2
diabetes, rescues core phenotypes in Fmr1-/y mice and selectively normalizes ERK
signaling, eIF4E phosphorylation and the expression of MMP-9. Thus, metformin is
a potential FXS therapeutic.
PMID- 28504729
TI - High-precision micro-displacement optical-fiber sensor based on surface plasmon
resonance.
AB - We propose and demonstrate a novel optical-fiber micro-displacement sensor based
on surface plasmon resonance (SPR) by fabricating a Kretschmann configuration on
graded-index multimode fiber (GIMMF). We employ a single-mode fiber to change the
radial position of the incident beam as the displacement. In the GIMMF, the angle
between the light beam and fiber axis, which is closely related to the resonance
angle, is changed by the displacement; thus, the resonance wavelength of the
fiber SPR shifts. This micro-displacement fiber sensor has a wide detection range
of 0-25 MUm, a high sensitivity with maximum up to 10.32 nm/MUm, and a nanometer
resolution with minimum to 2 nm, which transcends almost all of other optical
fiber micro-displacement sensors. In addition, we also research that increasing
the fiber polishing angle or medium refractive index can improve the sensitivity.
This micro-displacement sensor will have a great significance in many industrial
applications and provide a neoteric, rapid, and accurate optical measurement
method in micro-displacement.
PMID- 28504730
TI - Non-phase unwrapping interferometric approach for a real-time in-plane rotation
measurement.
AB - This Letter proposes a novel interferometric approach for the in-plane rotation
measurement. With a simple and compact measurement system, the rotation angle and
its direction can be determined simultaneously in real time by applying the
spatial carrier frequency. Besides, the phase unwrapping process is not required
for the angular evaluation, which simplifies the data processing procedure.
Theoretically, the relationship between the in-plane rotation and the phase
change distribution has been deduced to demonstrate the possibility of this
interferometric method. Practically, the preliminary experiments have been
carried out to verify the feasibility of this approach and quantify the
measurement accuracy.
PMID- 28504724
TI - Single-cell transcriptomics uncovers distinct molecular signatures of stem cells
in chronic myeloid leukemia.
AB - Recent advances in single-cell transcriptomics are ideally placed to unravel
intratumoral heterogeneity and selective resistance of cancer stem cell (SC)
subpopulations to molecularly targeted cancer therapies. However, current single
cell RNA-sequencing approaches lack the sensitivity required to reliably detect
somatic mutations. We developed a method that combines high-sensitivity mutation
detection with whole-transcriptome analysis of the same single cell. We applied
this technique to analyze more than 2,000 SCs from patients with chronic myeloid
leukemia (CML) throughout the disease course, revealing heterogeneity of CML-SCs,
including the identification of a subgroup of CML-SCs with a distinct molecular
signature that selectively persisted during prolonged therapy. Analysis of
nonleukemic SCs from patients with CML also provided new insights into cell
extrinsic disruption of hematopoiesis in CML associated with clinical outcome.
Furthermore, we used this single-cell approach to identify a blast-crisis
specific SC population, which was also present in a subclone of CML-SCs during
the chronic phase in a patient who subsequently developed blast crisis. This
approach, which might be broadly applied to any malignancy, illustrates how
single-cell analysis can identify subpopulations of therapy-resistant SCs that
are not apparent through cell-population analysis.
PMID- 28504732
TI - Automated technique to inscribe reproducible long-period gratings using a
CO2 laser splicer.
AB - We propose a technique to inscribe long period gratings (LPGs) in standard single
mode fibers (SSMFs). The proposed method uses a commercial CO2 splicer
that allows for the rotation of the fiber during laser irradiation, enabling a
uniform exposure around the fiber. LPGs inscribed in SSMFs with different periods
are presented. Gratings can be reproduced with a maximum difference between
resonant wavelength values of less than 1 nm. Furthermore, it is possible to
inscribe gratings with attenuation dips of -25 dB while at the same time
obtaining polarization-dependent losses as low as 2 dB.
PMID- 28504731
TI - Non-reciprocal geometric phase in nonlinear frequency conversion.
AB - We describe analytically and numerically the geometric phase arising from
nonlinear frequency conversion and show that such a phase can be made non
reciprocal by momentum-dependent photonic transition. Such non-reciprocity is
immune to the shortcomings imposed by dynamic reciprocity in Kerr and Kerr-like
devices. We propose a simple and practical implementation, requiring only a
single waveguide and one pump, while the geometric phase is controllable by the
pump and promises robustness against fabrication errors.
PMID- 28504733
TI - Uncloaking diffusive-light invisibility cloaks by speckle analysis.
AB - Within the range of validity of the stationary diffusion equation, an ideal
diffusive-light invisibility cloak can make an arbitrary macroscopic object
hidden inside of the cloak indistinguishable from the surroundings for all
colors, polarizations, and directions of incident visible light. However, the
diffusion equation for light is an approximation which becomes exact only in the
limit of small coherence length. Thus, one expects that the cloak can be revealed
by illumination with coherent light. The experiments presented here show that the
cloaks are robust in the limit of large coherence length but can be revealed by
analysis of the speckle patterns under illumination with partially coherent
light. Experiments on cylindrical core-shell cloaks and corresponding theory are
in good agreement.
PMID- 28504734
TI - Stochastic mirage phenomenon in a random medium.
AB - In the framework of geometric optics, we consider the problem of characterizing
the ray trajectory in a random medium with a mean refractive index gradient. Such
a gradient results in the mirage phenomenon where an object's observed location
is displaced from its actual location. We derive formulas for the mean ray path
in both the situation of isotropic stochastic fluctuations and an important
anisotropic case. For the isotropic model, the mean squared displacement is also
given by a simple formula. Our results could be useful for applications involving
the propagation of electromagnetic waves through the atmosphere, where larger
scale mean gradients and smaller-scale stochastic fluctuations are both present.
PMID- 28504735
TI - High sensitivity narrowband wavelength mid-infrared detection at room
temperature.
AB - We report an upconversion experiment using an orientation-patterned gallium
arsenide (OP-GaAs) crystal to detect small mid-infrared signals on an InGaAs
avalanche photodiode. A conversion efficiency up to 20% with a nonpolarized
pulsed fiber pump is demonstrated. Our uncooled setup is favorably compared in
terms of noise equivalent power, dynamic range, and response time to
cryogenically cooled HgCdTe detectors. Its dependence on the polarization of both
the pump and signal beams is also investigated.
PMID- 28504736
TI - Third-harmonic blue light generation from Kerr clustered combs and dispersive
waves.
AB - We demonstrated the deterministic generation of blue light emission (438 nm) via
the third-harmonic process from an infrared pump by carefully engineering the
dispersion of a high-quality-factor whispering gallery mode microcavity. We
present two different approaches to obtaining broad bandwidth light. One is based
on a clustered comb and the other employs a dispersive wave, and a broad Kerr
comb spanning a half-octave is obtained. This allowed frequency conversion over a
broad bandwidth ranging from 438 to 612 nm. This approach will enable the
development of micro-scale light sources and frequency converters for future
optical processing.
PMID- 28504738
TI - Photonics sensing at the thermodynamic limit.
AB - We report a slow-light fiber Bragg grating strain sensor with a resolution
limited by the extremely low thermodynamic phase fluctuations of the fiber. This
was accomplished by using a short grating (4.5 mm) to enhance the thermal phase
noise, an ultra-stable interrogation laser to lower the laser frequency noise,
and a slow-light mode with a high group index (~533) to suppress all other noise
sources. We demonstrate that in a similar but longer grating (21 mm), the phase
noise is suppressed in inverse proportion to the square root of the length, in
accordance with theory, leading to a strain resolution as low as 130
fepsilon/?Hz and a minimum detectable length of ~3*10-15 m at 1.5
kHz.
PMID- 28504737
TI - Multi-petawatt laser facility fully based on optical parametric chirped-pulse
amplification.
AB - We report on a multi-petawatt 3-cascaded all-optical parametric chirped-pulse
amplification laser facility. The experimental results demonstrate that the
maximum energy after the final amplifier and after the compressor is 168.7 J and
91.1 J, respectively. The pulse width (FWHM) is 18.6 fs in full width at half
maximum after optimization of pulse compression. Therefore, 4.9 PW peak power has
been achieved for the laser facility. To the best of our knowledge, this is the
highest peak power reported so far for an all-optical parametric chirped-pulse
amplification facility, and a compressed pulse shorter than 20 fs is achieved in
a PW-class laser facility for the first time.
PMID- 28504739
TI - Miniature multicore optical fiber vibration sensor.
AB - We demonstrate a compact and versatile interferometric vibration sensor that
operates in reflection mode. To build the device, a short segment of symmetric
strongly coupled multicore optical fiber (MCF) is fusion spliced to a single-mode
optical fiber (SMF). One end of the MCF segment is cleaved and placed in a
cantilever position. Due to the SMF-MCF configuration, only two supermodes are
excited in the MCF. Vibrations induce cyclic bending of the MCF cantilever which
results in periodic oscillations of the reflected interference spectrum. In our
device, the MCF itself is the inertial mass. The frequency range where our device
is sensitive can be easily tailored from a few hertz to several kilohertz through
the cantilever dimensions.
PMID- 28504740
TI - Nonresonant modes in plasmonic holey metasurfaces for the design of artificial
flat lenses.
AB - This Letter discusses nonresonant modes excited on holey metasurfaces and their
influence on the properties of spoof plasmonic states supported by the
metasurface when a second surface is placed in its proximity. We consider here a
metallic surface with periodic holes drilled in it. The field excited on each
hole is projected onto a set of nonresonant modes in order to discuss their
relative relevance. While previous simpler models assumed only the presence of
the fundamental mode, we show that the simultaneous presence of several modes
occurs when the surface is placed next to a metallic plate. Therefore, higher
order modes are responsible for the peculiar physical properties of wave
propagation of spoof plasmons between two surfaces, which can lead to new
gradient-index flat lenses for transceivers for space communications.
PMID- 28504741
TI - Real-time acquisition of complex optical fields by binary amplitude modulation.
AB - We describe, through simulations and experiments, a real-time wavefront
acquisition technique using random binary amplitude masks and an iterative phase
retrieval algorithm based on the Fresnel propagator. By using a digital
micromirror device, it is possible to recover an unknown complex object by
illuminating with this set of masks and simultaneously recording the resulting
intensity patterns with a high-speed camera, making this technique suitable for
dynamic applications.
PMID- 28504742
TI - Study of the interaction between graphene and planar terahertz metamaterial with
toroidal dipolar resonance.
AB - A planar terahertz metamaterial consisting of square split ring resonators is
proposed, and the excitation of toroidal dipolar resonance is demonstrated.
Moreover, we theoretically investigate the strong interaction between graphene
and toroidal dipolar resonance of the metamaterial. By varying its Fermi energy,
the simulations show that graphene can actively modulate the transmission
amplitude of toroidal dipolar resonance and even switch it off. The interaction
of the toroidal dipolar resonance with monolayer graphene further highlights the
ultrasensitive sensing characteristic of the planar metamaterial, which can be
utilized for other graphene-like two-dimensional materials. These intriguing
properties of the proposed metamaterial may have potential applications in
terahertz modulators and ultrasensitive sensors.
PMID- 28504743
TI - Accumulation-layer surface plasmons in transparent conductive oxides.
AB - A rigorous analytical study of the eigenmodes supported by a charge accumulation
layer within a transparent conductive oxide (TCO) is presented. The new class of
surface plasmons termed accumulation-layer surface plasmons (ASPs) is introduced.
Near resonance ASPs are tightly bound and display a vast effective index
tunability that could be of great practical interest. The suppression of ASPs in
the presence of epsilon-near zero regions is discussed.
PMID- 28504744
TI - Degenerate cavity supporting more than 31 Laguerre-Gaussian modes.
AB - Photons propagating in Laguerre-Gaussian modes have characteristic orbital
angular momenta, which are fundamental optical degrees of freedom. The orbital
angular momentum of light has potential application in high-capacity optical
communication and even in quantum information processing. In this work, we
experimentally construct a ring cavity with four lenses and four mirrors that is
completely degenerate for Laguerre-Gaussian modes. By measuring the transmitted
peaks and patterns of different modes, the ring cavity is shown to support more
than 31 Laguerre-Gaussian modes. The constructed degenerate cavity opens a new
way for using the unlimited resource of available angular momentum states
simultaneously.
PMID- 28504745
TI - 16 MHz wavelength-swept and wavelength-stepped laser architectures based on
stretched-pulse active mode locking with a single continuously chirped fiber
Bragg grating.
AB - We demonstrate a novel high-speed and broadband laser architecture based on
stretched pulse active mode locking that provides a wavelength-swept and
wavelength-stepped output. The laser utilizes a single intracavity 8.3 meter
chirped fiber Bragg grating to generate positive and negative dispersion, and can
be operated with or without an intracavity fixed Fabry-Perot etalon to generate
wavelength-swept and wavelength-stepped (frequency comb) outputs, respectively.
Using a four-path delay line at the output, we achieved 16.3 MHz repetition rates
and a 62 nm lasing bandwidth centered at 1550 nm. Single-sided double-pass
coherence lengths of 1.25 mm for the wavelength-swept configuration and more than
30 mm for the wavelength-stepped configuration were obtained. Relative intensity
noise was measured to be better than -140 dB/Hz. The stretched-pulse mode-locked
architecture utilizing long chirped fiber Bragg gratings offers a simple and
compact design for a broadband wavelength-tuned output at unprecedented speeds,
and can address the need for fast sources in applications such as optical
ranging, imaging, and sensing.
PMID- 28504746
TI - Ultrabroadband out-of-loop characterization of the carrier-envelope phase noise
of an offset-free Er:fiber frequency comb.
AB - Recent demonstrations of passively phase-locked fiber-based combs motivate
broadband characterization of the noise associated with the stabilized carrier
envelope offset frequency. In our study, we analyze the phase noise of a 100 MHz
Er:fiber system in a wide range spanning from microhertz to the Nyquist
frequency. An interferometric detection method enables analysis of the high
frequency output of an f-to-2f interferometer. The dominant contribution of a
broadband white noise floor at high frequencies attests quantum-limited
performance. An out-of-loop measurement of the carrier-envelope phase reveals its
jitter to be as low as 250 mrad when integrated over 12 orders of magnitude of
the radio-frequency spectrum.
PMID- 28504747
TI - Ultra-slow light propagation by self-induced transparency in ruby in the
superhyperfine limit.
AB - Self-induced transparency is reported for circularly polarized light in the
R1(-3/2) line of a 30 ppm ruby (alpha
Al2O3:Cr3+) at 1.7 K in a magnetic field of
B||c=4.5 T. In such a field and temperature, a 30 ppm ruby is in the so-called
superhyperfine limit resulting in a long phase memory time, TM=50
MUs, and a thousand-fold slower pulse propagation velocity of ~300 m/s was
observed, compared to the ~300 km/s measured in the first observation of self
induced transparency (SIT) ~50 years ago, that employed a ruby with a 500 ppm
chromium concentration in zero field and at 4.2 K. To date, this is the slowest
pulse propagation ever observed in a SIT experiment.
PMID- 28504748
TI - Terahertz multilevel phase Fresnel lenses fabricated by laser patterning of
silicon.
AB - Multilevel phase Fresnel lenses (MPFLs) with a high numerical aperture for 0.58
THz frequencies were developed. The components based on a monocrystalline silicon
wafer are prepared by patterning by a high-speed industrial-scale laser direct
writing (LDW) system. Two consistent series of the terahertz-MPFLs with phase
quantization levels varying between 2 and the continuous kinoform shape for the
focal lengths of 5 and 10 mm were produced employing inherent flexibility of the
LDW fabrication process. The focusing performance was studied at the optimal 0.58
THz frequency using a Gaussian beam profile and scanning 2D intensity
distribution with a terahertz detector along the optical axis. The efficiency of
the terahertz-MPFL was found to be dependent of the number of subzones. The
position and orientation angles of the patterned plane of the silicon wafer were
considered to reduce the effect of standing waves formation in the experiment.
PMID- 28504749
TI - Designing ultrabroadband absorbers based on Bloch theorem and optical topological
transition.
AB - In this Letter, we propose a method to design ultrabroadband near-perfect
absorbers, consisting of a periodic dielectric-metal multilayer. In the method,
the Bloch theorem and optical topological transition (OTT) of iso-frequency
surfaces are employed to manipulate the start and end of the near-perfect
spectral absorption band, respectively. Moreover, we design and fabricate an
ultrabroadband near-perfect absorber utilizing the proposed method. The average
absorption of the designed absorber is ~95% in the focused visible and near
infrared range (0.4-2 MUm). This omnidirectional and polarization-independent
near-perfect absorber is promising for solar energy harvesting, emissivity
control, and thermal imaging.
PMID- 28504750
TI - Self-compression of femtosecond deep-ultraviolet pulses by filamentation in
krypton.
AB - We demonstrate self-compression of deep-ultraviolet (DUV) pulses by filamentation
in krypton. In contrast to self-compression in the near-infrared, that in the DUV
is associated with a red-shifted sub-pulse appearing in the pulse temporal
profile. The achieved pulse width of 15 fs is the shortest among demonstrated sub
mJ deep-ultraviolet pulses.
PMID- 28504751
TI - Highly scalable femtosecond coherent beam combining demonstrated with 19 fibers.
AB - Coherent beam combining in the femtosecond regime of a record number of 19 fibers
is demonstrated. The interferometric phase measurement technique, particularly
well suited to phase-lock a very large number of fibers, is successfully
demonstrated in the femtosecond regime. A servo loop is implemented to control
piezoelectric fiber stretchers for both phase and delay variation compensation.
The residual phase errors are below lambda/60 rms. Nearly 50% of the total
energy is contained in the far-field central lobe. After compression, we obtain a
combined pulse width of 300 fs identical to the master oscillator pulse width.
PMID- 28504752
TI - Large-scale nanostructured low-temperature solar selective absorber.
AB - A large-scale nanostructured low-temperature solar selective absorber is
demonstrated experimentally. It consists of a silicon dioxide thin film coating
on a rough refractory tantalum substrate, fabricated based simply on self
assembled, closely packed polystyrene nanospheres. Because of the strong light
harvesting of the surface nanopatterns and constructive interference within the
top silicon dioxide coating, our absorber has a much higher solar absorption
(0.84) than its planar counterpart (0.78). Though its absorption is lower than
that of commercial black paint with ultra-broad absorption, the greatly
suppressed absorption/emission in the long range still enables a superior heat
accumulation. The working temperature is as high as 196.3 degrees C under 7-sun
solar illumination in ambient conditions-much higher than those achieved by the
two comparables.
PMID- 28504753
TI - Second-harmonic focusing by a nonlinear turbid medium via feedback-based
wavefront shaping.
AB - Scattering has usually been considered detrimental for optical focusing or
imaging. Recently, more and more research has shown that strongly scattering
materials can be utilized to focus coherent light by controlling or shaping the
incident light. Here, purposeful focusing of second-harmonic waves, which are
generated and scattered from nonlinear turbid media via feedback-based wavefront
shaping, is presented. This Letter shows a flexible manipulation of both
disordered linear and nonlinear scattering signals, indicating more controllable
degrees of freedom for the description of turbid media. This technique also
provides a possible way to an efficient transmission of nonlinear signal at a
desired location in the form of a focal point or other patterns. With the
combination of random nonlinear optics and wavefront shaping methods, more
interesting applications can be expected in the future, such as nonlinear
transmission matrix, multi-frequency imaging, and phase-matching-free nonlinear
optics.
PMID- 28504754
TI - Performance comparison of pseudo-inverse and maximum-likelihood estimators of
Stokes parameters in the presence of Poisson noise for spherical design-based
measurement structures.
AB - Estimation of the Stokes vector from N>4 intensity measurements is usually
performed with the pseudo-inverse (PI) estimator, which is optimal when the noise
that corrupts the measurements is additive and Gaussian. In the presence of
Poisson shot noise, the maximum-likelihood (ML) estimator is different from the
PI estimator, but is more complex to implement since it is not closed-form. We
compare in this Letter the precisions obtained with the ML and the PI estimators
in the presence of Poisson noise when using measurement structures based on
spherical designs. We show that, in this case, the gain in precision brought by
the ML estimator is real but modest, so that in applications where processing
speed is an issue, the PI estimator can be considered sufficient. This result is
important in the choice of the inversion strategy for Stokes polarimetry.
PMID- 28504755
TI - Resolving 1 million sensing points in an optimized differential time-domain
Brillouin sensor.
AB - A differential pulse-width pair (DPP) Brillouin distributed fiber sensor is
implemented to achieve centimetric spatial resolution over distances of several
kilometers. The presented scheme uses a scanning method in which the spectral
separation between the two probe sidebands is kept constant, while the optical
frequency of the pump is swept to scan the Brillouin spectral response.
Experimental results show that this method avoids detrimental temporal
distortions of the pump pulses, which in a standard implementation prevent the
DPP method from operating over mid-to-long distances. Such a novel scanning
procedure allows the resolving, for the first time in pure time-domain Brillouin
sensors, of 1,000,000 sensing points, i.e., 1 cm spatial resolution over 10 km in
a conventional acquisition time.
PMID- 28504756
TI - Active modulation of the terahertz spectra radiated from two air plasmas.
AB - A simple and energy-saving method has been proposed to actively modulate the
spectra of terahertz (THz) waves radiated from two serial plasmas, which uses the
background light to generate one plasma to make full use of the energy of the
femtosecond laser. With this method, the modulation of the central frequency,
spectral bandwidth, and spectral profile of the output THz waves have been
observed. The shifting of the amplitude dip has been manipulated by changing the
distance of the two serial plasmas. The manipulation results agree with the ones
simulated by the transition-Cherenkov model. This proposed method provides a
useful tool for getting the modulated THz spectra that can be used in the THz
remote sensing.
PMID- 28504757
TI - Absolute frequency measurements of CHF3 Doppler-free ro-vibrational
transitions at 8.6 MUm.
AB - We report on absolute measurements of saturated-absorption line-center
frequencies of room-temperature trifluoromethane using a quantum cascade laser at
8.6 MUm and the frequency modulation spectroscopy method. Absolute calibration of
the laser frequency is obtained by direct comparison with a mid-infrared optical
frequency comb synthesizer referenced to a radio-frequency Rb standard. Several
sub-Doppler transitions falling in the upsilon5 vibrational band are
investigated at around 1158.9 cm-1 with a fractional frequency
precision of 8.6.10-12 at 1-s integration time, limited by the Rb
clock stability. The demonstrated frequency uncertainty of 6.6.10-11
is mainly limited by the reproducibility of the frequency measurements.
PMID- 28504758
TI - Pulse picker for synchrotron radiation driven by a surface acoustic wave.
AB - A functional test for a pulse picker for synchrotron radiation was performed at
Diamond Light Source. The purpose of a pulse picker is to select which pulse from
the synchrotron hybrid-mode bunch pattern reaches the experiment. In the present
work, the Bragg reflection on a Si/B4C multilayer was modified using
surface acoustic wave (SAW) trains. Diffraction on the SAW alters the direction
of the x rays and it can be used to modulate the intensity of the x rays that
reach the experimental chamber. Using electronic modulation of the SAW amplitude,
it is possible to obtain different scattering conditions for different x-ray
pulses. To isolate the single bunch, the state of the SAW must be changed in the
short time gap between the pulses. To achieve the necessary time resolution, the
measurements have been performed in conical diffraction geometry. The achieved
time resolution was 120 ns.
PMID- 28504759
TI - Reconfigurable opto-thermal graded-index waveguiding in bulk chalcogenide
glasses.
AB - In the absence of suitable deposition processes, the fabrication of graded-index
chalcogenide waveguides or fibers remains an outstanding challenge. Here, by
exploiting the strong thermo-optic effect present in chalcogenide glasses, we
experimentally demonstrate non-permanent optically-induced waveguides in bulk
As2Se3 rods using a 1.55 MUm wavelength laser. This single
step process can be used not only to self-trap the writing beam, but also to
guide another optical beam at a different wavelength in the opto-thermally
inscribed waveguide channel. These results could pave the way towards harnessing
nonlinear effects in graded-index chalcogenide guided settings.
PMID- 28504760
TI - Programmable controlled mode-locked fiber laser using a digital micromirror
device.
AB - A digital micromirror device (DMD)-based arbitrary spectrum amplitude shaper is
incorporated into a large-mode-area photonic crystal fiber laser cavity. The
shaper acts as an in-cavity programmable filter and provides large tunable
dispersion from normal to anomalous. As a result, mode-locking is achieved in
different dispersion regimes with watt-level high output power. By programming
different filter profiles on the DMD, the laser generates femtosecond pulse with
a tunable central wavelength and controllable bandwidth. Under conditions of
suitable cavity dispersion and pump power, design-shaped spectra are directly
obtained by varying the amplitude transfer function of the filter. The results
show the versatility of the DMD-based in-cavity filter for flexible control of
the pulse dynamics in a mode-locked fiber laser.
PMID- 28504761
TI - High-reflectance magnetron-sputtered scandium-based x-ray multilayer mirrors for
the water window.
AB - We present an experimental comparison of several Sc-based short period multilayer
mirrors including Cr/Sc with B4C barrier layers and
CrNx/Sc, and we propose a new material combination that provides high
reflectance in the water window domain. Multilayer samples with period thickness
in the range 1.5-1.7 nm have been deposited by magnetron sputtering and
characterized by x-ray reflectometry with a Cu-Kalpha source and with synchrotron
radiation near the Sc-L2,3 edge. Best results are achieved by
combining the nitridation of Cr layers and the addition of B4C barrier
layers. Near normal incidence reflectance as high as 23% has been measured at
photon energy of 397 eV. A simulation model of the multilayer structure is
proposed and it predicts that reflectance higher than 32% is achievable with
CrNx/B4C/Sc mirrors.
PMID- 28504762
TI - Surface enhanced infrared absorption of chemisorbed carbon monoxide using
plasmonic nanoantennas.
AB - We report the enhancement of infrared absorption of chemisorbed carbon monoxide
on platinum in the gap of plasmonic nanoantennas. Our method is based on the self
assembled formation of platinum nanoislands on nanoscopic dipole antenna arrays
manufactured via electron beam lithography. We employ systematic variations of
the plasmonic antenna resonance to precisely couple to the molecular stretch
vibration of carbon monoxide adsorbed on the platinum nanoislands. Ultimately, we
reach more than 1500-fold infrared absorption enhancements, allowing for an
ultrasensitive detection of a monolayer of chemisorbed carbon monoxide. The
developed procedure can be adapted to other metal adsorbents and molecular
species and could be utilized for coverage sensing in surface catalytic
reactions.
PMID- 28504763
TI - Mirrors with designed spherical aberration for multi-pass cavities.
AB - We present a novel multi-pass cavity design based on the use of a rotationally
symmetric end mirror having a specifically designed spherical aberration so that
its focal length varies inversely as the ray height from the optical axis. We
provide a detailed discussion of how ray tracing can be done for this system and
show with numerical simulations that a very rich set of exotic spot patterns can
be formed on the end mirrors. We further show a specific q-preserving
configuration where the q-parameters of the input and output beams remain the
same. Finally, we derive the polar form of the mirror surface profile that gives
this offset-dependent focal length.
PMID- 28504764
TI - Enhanced performance in serial-to-parallel data conversion via Raman-assisted
time lens processing.
AB - We have demonstrated a new approach to enhance the uniformity of conversion
efficiency in serial-to-parallel data conversion via time lens processing. In our
approach, Raman amplification is applied to enhance four-wave mixing in a highly
nonlinear fiber. By carefully selecting the pump wavelength, the Raman gain
profile can be exploited to compensate the roll-off in conversion efficiency
resulted from the varying phase mismatch between the linearly chirped pump and
the signal. With Raman amplification, improvement of sensitivity up to 6.8 dB has
been experimentally obtained. The variation of sensitivity across the output
channels has been reduced from 8.4 to 2.0 dB.
PMID- 28504765
TI - Thermo-optic characteristic of DNA thin solid film and its application as a
biocompatible optical fiber temperature sensor.
AB - We report unique thermo-optical characteristics of DNA-Cetyl tri-methyl ammonium
(DNA-CTMA) thin solid film with a large negative thermo-optical coefficient of
3.4*10-4/ degrees C in the temperature range from 20 degrees C to 70
degrees C without any observable thermal hysteresis. By combining this thermo
optic DNA film and fiber optic multimode interference (MMI) device, we
experimentally demonstrated a highly sensitive compact temperature sensor with a
large spectral shift of 0.15 nm/ degrees C. The fiber optic MMI device was a
concatenated structure with single-mode fiber (SMF)-coreless silica fiber (CSF)
single mode fiber (SMF) and the DNA-CTMA film was deposited on the CSF. The
spectral shifts of the device in experiments were compared with the beam
propagation method, which showed a good agreement.
PMID- 28504766
TI - Direct stabilization of optomechanical oscillators.
AB - We demonstrate a simple and effective technique for stabilizing the oscillation
amplitude of a radiation pressure driven RF optomechanical oscillator (OMO). By
controlling the optomechanical gain through a feedback loop that uses the
oscillation amplitude itself as the feedback parameter, we have been able to
suppress the amplitude fluctuations and drift. In contrast to more complex
techniques that only lock the relative wavelength detuning, the proposed
technique isolates the oscillation amplitude not only from laser wavelength
variations, but also from laser power variations, ambient temperature variations,
and coupling gap variations. The amplitude stabilization also improves the
stability of the oscillation frequency (compared to free-running OMOs).
PMID- 28504767
TI - Cavity-enhanced thermo-optic bistability and hysteresis in a graphene-on
Si3N4 ring resonator.
AB - Cavity-enhanced thermo-optic bistability is studied in a graphene-on
Si3N4 ring resonator. By engineering the coverage of the
monolayer graphene on top of the Si3N4 ring resonator, we
observed a two-fold enhancement in the thermo-optically induced resonance shift
rate and an 18-fold increase in the effective thermal nonlinear refractive index
compared with the devices without graphene. The thermo-optic hysteresis loop was
also characterized in this hybrid structure, where the experimental results agree
well with the theoretical calculations. This Letter paves the way for graphene-on
Si3N4-based high-speed photodetectors, modulators, and
devices for on-chip nonlinear optical applications.
PMID- 28504768
TI - Spatial integration by a dielectric slab and its planar graphene-based
counterpart.
AB - In this contribution a new approach to perform spatial integration is presented
using a dielectric slab. Our approach is indeed based on the fact that the
transmission coefficient of a simple dielectric slab at its mode excitation angle
matches the Fourier-Green's function of first-order integration. Inspired by the
mentioned dielectric-based integrator, we further demonstrate its graphene-based
counterpart. The latter is not only reconfigurable but also highly miniaturized
in contrast to the previously reported designs [Opt. Commun.338, 457
(2015)OPCOB80030-401810.1016/j.optcom.2014.11.007]. Such integrators have the
potential to be used in ultrafast analog computation and signal processing.
PMID- 28504769
TI - Semitransparent and flexible perovskite solar cell with high visible
transmittance based on ultrathin metallic electrodes.
AB - We have fabricated semitransparent and flexible indium-free perovskite solar
cells (PeSCs) with high visible transmittance employing two kinds of composite
ultrathin metallic electrodes, MoO3/Au and
MoO3/Au/Ag/MoO3/Alq3, as the bottom and top
electrodes, respectively. These electrodes show superb electrical conductivity,
excellent mechanical robustness, and high optical transparency which are quite
suitable for semitransparent and flexible PeSCs. An overall power conversion
efficiency (PCE) of 6.96% and an average visible transmittance of 18.16% in the
wavelength range of 380-790 nm were achieved. Furthermore, the devices maintained
71% of their initial PCE after 1000 bending cycles with a bending radius of 4 mm.
PMID- 28504770
TI - Umov effect in single-scattering dust particles: effect of irregular shape.
AB - The Umov effect manifests itself as an inverse correlation between the light
scattering maximum of positive polarization Pmax and the geometric
albedo A of the target. In logarithmic scales, Pmax is linearly
dependent on A. This effect has been long known in the optics of particulate
surfaces and, recently, it was extended for the case of single-scattering dust
particles whose size is comparable to the wavelength of the incident light. In
this work, we investigate the effect of irregular shape on the Umov effect in
single-scattering particles. Using the discrete dipole approximation (DDA), we
model light scattering by two different types of irregularly shaped particles.
Despite significant differences in their morphology, both types of particles
reveal remarkably similar diagrams of log(Pmax) versus log(A).
Moreover, in a power-law size distribution r-n with n=2.5-3.0, the
Umov diagrams in both types of particles nearly coincide. This suggests little
dependence on the shape of target particles in the retrieval of their reflectance
using the Umov effect.
PMID- 28504771
TI - Laguerre-Gaussian modal q-plates.
AB - We propose space-variant uniaxial flat optical elements designed to generate pure
Laguerre-Gaussian modes with arbitrary azimuthal and radial indices l and p from
an incident Gaussian beam. This is done via the combined use of the dynamic and
the geometric phases. Optimal design protocol for the mode conversion efficiency
is derived, and the corresponding characteristics are given for -6<=l<=6 and
0<=p<=5. The obtained "modal q-plates" may find many applications whenever the
radial degree of freedom of a light field is at play.
PMID- 28504772
TI - Patient flow in Acute Medical Units. A design approach to flow improvement.
PMID- 28504773
TI - Challenges and 'obstacles': reframing our perspective on the transition into
adulthood for young people with life-limiting and life-threatening conditions.
PMID- 28504774
TI - Yoshinori Ohsumi's Nobel Prize for mechanisms of autophagy: from basic yeast
biology to therapeutic potential.
AB - On 3 October 2016, Japanese cell biologist Yoshinori Ohsumi was awarded the Nobel
Prize in Physiology or Medicine 'for his discoveries of mechanisms for
autophagy'; autophagy being an intracellular degradation pathway that helps
maintain cytoplasmic homeostasis. This commentary discusses Ohsumi's Nobel prize
winning work in context, before explaining the clinical relevance of autophagy.
PMID- 28504775
TI - Efficacy of epidural blood patches for spontaneous low-pressure headaches: a case
series.
AB - Patients with a spontaneous cerebrospinal fluid leak, normally at a spinal level,
typically present with low-pressure headache. In refractory cases, an epidural
blood patch may be attempted. We aimed to assess the efficacy of lumbar epidural
blood patching in spontaneous, low-pressure headaches. Methods We retrospectively
analysed notes of patients who had an epidural blood patch performed for
spontaneous low-pressure headaches in a single centre. Information regarding
demographics, radiology and clinic follow-up was extracted from an electronic
patient record system. Questionnaires regarding outcome were sent to patients a
minimum of 6 months post-procedure. All patients received an epidural blood patch
in the lumbar region irrespective of the site of cerebrospinal fluid leak.
Results Sixteen patients who underwent lumbar epidural blood patching were
analysed (11 female; mean age 43 years). The site of cerebrospinal fluid leak was
evident in only 3/16 patients. Thirteen patients attended clinic follow-up; three
reported complete headache resolution, four reported improvement in intensity or
frequency and six described no change. Five of eight questionnaire respondents
reported reduction in pain, and in these responders, mean headache severity
improved from 9/10 to 3/10. Five of eight patients returning follow-up
questionnaires reported sustained improvement in headache symptoms. Conclusion
Epidural blood patch procedures can provide sustained improvement in headache
symptoms in selected patients with spontaneous intracranial hypotension, but an
untargeted approach has a lower success rate than reported in other case series.
PMID- 28504776
TI - Insulin-mediated hypoglycaemia secondary to recurrent clear cell renal carcinoma.
AB - Renal cell carcinoma has previously been associated with hypoglycaemia in the
setting of non-islet cell tumours, caused by a paraneoplastic phenomenon relating
to the production of insulin-like growth factor type II. We present a case of
recurrent clear cell renal cell carcinoma, leading to an insulin-mediated
paraneoplastic phenomenon causing severe recurrent hypoglycaemia. Hypoglycaemina
was managed successfully using diazoxide therapy, in conjunction with pazopanib
and radiotherapy to reduce tumour burden.
PMID- 28504777
TI - Dengue fever with compartment syndrome of the right arm.
AB - A 44-year-old woman was admitted to our hospital with dengue fever. She developed
a haematoma in the right arm at the site of a previous arterial line insertion.
Due to coexisting thrombocytopenia, the bleeding was severe enough to cause
compartment syndrome. An emergency fasciotomy was performed and her limb
salvaged. The case illustrates one important potential complication of this
common infectious disease.
PMID- 28504778
TI - Chorea in the older adult: a full blooded answer.
AB - Chorea is a severe, distressing, movement disorder characterised by excessive,
purposeless movements of the limbs, head and orofacial muscles in a generalised
and irregularly-timed fashion. In young patients, neurodegenerative (Huntington's
disease) and metabolic (Wilson's disease) aetiologies are most common. In the
older population, the differential widens to include genetic, structural,
metabolic and pharmacological causes. We present a case of an older man who
developed progressive choreoathetosis secondary to polycythaemia vera which
resolved with serial venesections. The treatment of his underlying condition is
discussed.
PMID- 28504779
TI - Unilateral retinal racemose haemangioma with cataract.
PMID- 28504780
TI - Is tenofovir the answer to further preventing mother-to-child transmission of
hepatitis B?
PMID- 28504781
TI - Expanding the evidence base in the pharmacological management of vasovagal
syncope - the next POST.
PMID- 28504782
TI - Fatal Accident Inquiries: raising awareness of their role in relation to the
medical profession in Scotland.
PMID- 28504783
TI - Reading books and reading patients: can Book Clubs help both?
PMID- 28504784
TI - Current clinical controversies in the management of sepsis.
AB - Sepsis remains a challenging clinical problem requiring prompt diagnosis and
optimal clinical management if the continuing high mortality is to be contained.
In this brief review I consider four specific questions that are the subject of
ongoing controversy. First, whether the new 'Sepsis-3' definitions will be
helpful, in particular in improving diagnosis, or whether the rapid move towards
precision medicine will make the definition redundant. Second, should we
routinely use combinations of antibiotics for the empiric treatment of sepsis.
Third, whether there is any clinical benefit in continuous rather than bolus
administration of beta-lactam antibiotics. Finally, whether there is good
evidence that biomarkers such as procalcitonin can help reduce the duration of
antibiotic therapy.
PMID- 28504785
TI - Addressing noncommunicable diseases in primary care: the case of type 2 diabetes.
AB - The rapid growth of noncommunicable diseases represents a formidable global
health challenge. Here we use type 2 diabetes as a case study to illustrate the
rise of noncommunicable diseases and call attention to the important role of
primary care systems in addressing these diseases in low- and middle-income
countries. Comprehensive screening for diabetes should be implemented through
primary care systems to increase early detection of prediabetes and undiagnosed
diabetes - a first step to diabetes prevention and management. In addition,
primary care systems should strengthen and expand capacity to link patients to
appropriate interventions based on their diabetes status and provide care
coordination (e.g. leveraging task-shifting and technology), and integrate clinic
and community resources for diabetes prevention and control. Additional
strategies should include continuous quality improvement, health systems
strengthening, workforce development, and affordable and sustainable financing.
Together, these actions could elevate the role of primary care in addressing
diabetes in low- and middle-income countries and help advance global progress
towards reducing diabetes complications, and also preventing or delaying diabetes
among those at risk.
PMID- 28504786
TI - The way we die now: a personal reflection.
PMID- 28504787
TI - Medical humanities: some uses and problems.
AB - The arts and humanities were allowed into the British medical curriculum in 1993
when the General Medical Council re-structured it in a paper entitled 'Tomorrow's
Doctors'. Since then many medical schools have developed humanities modules and
the broad term 'medical humanities' refers to these. They can contribute to
medical education in at least three ways: as a supplement to what is already in
the curriculum, especially for ethics and communication; as an outside critique
of medical practice; and to personal and professional development. Nevertheless,
there are practical problems concerning appropriate teachers and methods of
assessment. Moreover, the dominant interest is now academic research rather than
education.
PMID- 28504788
TI - Are medical eponyms really dying out? A study of their usage in the historical
biomedical literature.
AB - Eponyms are a prominent feature of medical language. Many feel they have had
their time and serve only to complicate medical education and conversation.
Others argue that eponyms can make unmemorable concepts memorable, can concisely
label complex concepts, and promote a valuable interest in medical history. It is
frequently assumed that medical eponyms are marching towards extinction. However,
this hypothesis has not been adequately tested. The fate of 8,636 eponyms from
contemporary and historical registers is presented here. The annual usage of each
eponym in PubMed indexed articles since 1900 is analysed with metrics of eponym
prevalence, coinage and extinction. The fate of eponyms named for those
implicated in Nazi war crimes is also measured. The analysis shows that more
publications used an eponym in their title in 2014 than ever before. However, the
proportion using an eponym title has fallen from a peak of 3% in 1991 to 2%
today, while annual extinction of eponyms overtook coinage in the 1980s. This
suggests that, while not in dramatic decline, they are perhaps losing market
share to more scientific descriptions. There is no ambiguity in the fate of
eponyms related to Nazi war crimes which have almost entirely fallen out of use
in the last decade.
PMID- 28504789
TI - Personalised approach to anticoagulation
PMID- 28504790
TI - Fast tuning of covalent triazine frameworks for photocatalytic hydrogen
evolution.
AB - A fast and facile route for the optimization of covalent triazine frameworks
(CTFs) for photocatalytic hydrogen production is presented. Within 10 minutes a
CTF with low photocatalytic activity can be converted into a highly active
photocatalyst. Optimized CTF catalysts show an average hydrogen evolution rate of
1072 MUmol h-1 g-1 under visible light (>420 nm).
PMID- 28504791
TI - Mapping gas phase dipeptide motions in the far-infrared and terahertz domain.
AB - Vibrational signatures of Ac-Phe-AA-NH2 dipeptides are recorded and analysed in
the far IR/THz spectral domain (100-800 cm-1, 3-24 THz), with the 'AA' amino acid
chosen within the series 'AA' = Gly, Ala, Pro, Cys, Ser, Val. Phe stands for
phenylalanine. IR-UV ion dip experiments are conducted on the free electron laser
FELIX and combined with DFT-based molecular dynamics simulations for the
calculation of the dynamical anharmonic vibrational spectra. The excellent
agreements between the experimental and theoretical spectra of the Ac-Phe-AA-NH2
series allow us to make detailed and unambiguous mapping of the vibrational
motions into three main domains: 700-800 cm-1 for C-H waggings, 400-700 cm-1 for
N-H waggings, with a one-to-one signature per amide N-H backbone group, 0-400 cm
1 for delocalized and large amplitude collective motions over the dipeptide
backbone, with backbone torsional motions arising <100 cm-1.
PMID- 28504792
TI - Cu(iii)triarylcorroles with asymmetric push-pull meso-substitutions: tunable
molecular electrochemically catalyzed hydrogen evolution.
AB - The synthesis of four low symmetry A2B type Cu(iii)triarylcorroles with meso-aryl
substituents that provide electron donating (push) and withdrawing (pull)
properties is reported, along with their structural characterization by NMR
spectroscopy and X-ray crystallography. An analysis of the structure-property
relationships in the optical and redox properties has been carried out by
comparing their optical spectroscopy, electrochemistry, and
spectroelectrochemistry to trends predicted in DFT and TD-DFT calculations. The
results demonstrate that A2B type Cu(iii)triarylcorroles are highly efficient
catalysts for electrocatalyzed hydrogen evolution reactions (HERs) and that their
reactivity can be modulated by changing the nature of the B-position meso
substituent.
PMID- 28504794
TI - Reactive oligo(dimethylsiloxane) mesogens and their nanostructured thin films.
AB - Oligo(dimethylsiloxane)-based reactive mesogens were prepared and shown to form
room-temperature smectic phases which were 'frozen-in' by photopolymerization.
Homeotropically aligned, nanostructured thin films were obtained by spincoating,
and micropatterning was demonstrated. These hybrid reactive mesogens are suitable
for the preparation of aligned nanostructured polymer thin films with potential
applications ranging from stimuli responsive coatings to nanoporous membranes.
PMID- 28504793
TI - Generating single metalloprotein crystals in well-defined redox states:
electrochemical control combined with infrared imaging of a NiFe hydrogenase
crystal.
AB - We describe an approach to generating and verifying well-defined redox states in
metalloprotein single crystals by combining electrochemical control with
synchrotron infrared microspectroscopic imaging. For NiFe hydrogenase 1 from
Escherichia coli we demonstrate fully reversible and uniform electrochemical
reduction from the oxidised inactive to the fully reduced state, and temporally
resolve steps during this reduction.
PMID- 28504796
TI - Formation of high-molecular weight polyaminoborane by Fe hydride catalysed
dehydrocoupling of methylamine borane.
AB - The complex [(PNHP)Fe(H)(CO)(HBH3)] (PNHP = HN(CH2CH2Pi-Pr2)2) serves as a
catalyst precursor for the selective dehydrocoupling of methylamine borane at
room temperature, tentatively via an off-metal polymerisation pathway.
PMID- 28504797
TI - Advancing polyethylene properties by incorporating NO2 moiety in 1,2
bis(arylimino)acenaphthylnickel precatalysts: synthesis, characterization and
ethylene polymerization.
AB - A new family of nickel halides (bromides Ni1-Ni5 and chlorides Ni6-Ni10) ligated
by 1-(2,6-dibenzhydryl-4-nitrophenylimino)-2-(arylimino)acenaphthylene (Aryl =
2,6-Me2C6H3L1, 2,6-Et2C6H3L2, 2,6-iPr2C6H3L3, 2,4,6-Me3C6H2L4, and 2,6-Et2-4
MeC6H2L5) have been prepared and well characterized, and the scope of their
catalytic properties toward the polymerization of ethylene has been investigated.
Upon activation with either Et2AlCl or EASC, the nickel bromide complexes
displayed better activities than their nickel chloride counterparts and produced
higher-molecular-weight polyethylene in the range of 106 g mol-1 with a very
narrow range of molecular weight distributions. In comparison with reference
precatalysts with non-nitro substituents (CH3, F or Cl), the title complexes
experienced a modest negative effect on catalytic activity upon replacement with
a NO2 moiety (activity up to 4.61 * 106 g PE (mol Ni)-1 h-1 at 20 degrees C).
Conversely, the NO2 moiety exerted a positive effect to increase the molecular
weight of the resulting polyethylene, and Ni4/Et2AlCl gave polyethylene with a
maximum molecular weight of as high as 32.8 * 105 g mol-1, which is not only the
highest among the title complexes but also higher than any literature values
reported with 1,2-diiminoacenaphthylnickel halides.
PMID- 28504795
TI - Label-free detection of DNA hybridization with a compact LSPR-based fiber-optic
sensor.
AB - A miniaturized, robust, localized surface plasmon resonance (LSPR)-coupled fiber
optic (FO) nanoprobe providing an integrated and portable solution for detection
of DNA hybridization and measurement of DNA concentrations has been demonstrated.
The FO nanoprobe was created by constructing arrays of metallic nanostructures on
the end facets of optical fibers utilizing nanofabrication technologies,
including electron beam lithography and lift-off processes. The LSPR-FO nanoprobe
device offers real-time, label-free, and low-sample-volume quantification of
single-strand DNA in water with high sensitivity and selectivity, achieving a
limit of detection around 10 fM. These results demonstrate the feasibility of the
LSPR-FO nanoprobe device as a compact and low-cost biosensor for detection of
short-strand DNA.
PMID- 28504798
TI - A vacuum ultraviolet photoionization study on high-temperature decomposition of
JP-10 (exo-tetrahydrodicyclopentadiene).
AB - Two sets of experiments were performed to unravel the high-temperature pyrolysis
of tricyclo[5.2.1.02,6] decane (JP-10) exploiting high-temperature reactors over
a temperature range of 1100 K to 1600 K, Advanced Light Source (ALS), and 927 K
to 1083 K, National Synchrotron Radiation Laboratory (NSRL), with residence times
of a few tens of microseconds (ALS) to typically 144 ms (NSRL). The products were
identified in situ in supersonic molecular beams via single photon vacuum
ultraviolet (VUV) photoionization coupled with mass spectroscopic detection in a
reflectron time-of-flight mass spectrometer (ReTOF). These studies were designed
to probe the initial (ALS) and also higher order reaction products (NSRL) formed
in the decomposition of JP-10 - including radicals and thermally labile closed
shell species. Altogether 43 products were detected and quantified including C1
C4 alkenes, dienes, C3-C4 cumulenes, alkynes, eneynes, diynes, cycloalkenes,
cyclo-dienes, aromatic molecules, and most importantly, radicals such as ethyl,
allyl, and methyl produced at shorter residence times. At longer residence times,
the predominant fragments were molecular hydrogen (H2), ethylene (C2H4), propene
(C3H6), cyclopentadiene (C5H6), cyclopentene (C5H8), fulvene (C6H6), and benzene
(C6H6). Accompanied by electronic structure calculations, the initial JP-10
decomposition via C-H bond cleavages resulting in the formation of the initial
six C10H15 radicals was found to explain the formation of all products detected
in both sets of experiments. These radicals are not stable under the experimental
conditions and further decompose via C-C bond beta-scission processes. These
pathways result in ring opening in the initial tricyclic carbon skeletons of JP
10. Intermediates accessed after the first beta-scission can further isomerize or
dissociate. Complex PAH products in the NRLS experiment (naphthalene,
acenaphthylene, biphenyl) are likely formed via molecular growth reactions at
elevated residence times.
PMID- 28504800
TI - Experimental and computational study of the magnetic properties of ZrMn2
xCoxGe4O12.
AB - Polycrystalline samples in the solid solution ZrMn2-xCoxGe4O12 (x = 0.0, 0.5,
1.0, 1.5 and 2.0) have been prepared using the ceramic method and characterised
by a combination of magnetometry, X-ray diffraction and neutron diffraction. They
all adopt the space group P4/nbm with a ~ 9.60, c ~ 4.82 A and show long-range
magnetic order with transition temperatures, TC, in the range 2 <= TC/K <= 10.
The underlying magnetic structure is the same in each case but the ordered spins
lie along [001] when x = 0.0 and in the (001) plane for all other compositions.
In all cases the magnetically-ordered phase is a weak ferromagnet although the
magnitude of the spontaneous magnetisation and the strength of the coercive field
are composition-dependent. The magnetic structure can be rationalized by
considering the strengths of the interactions along the distinct M-O-Ge-O-M
superexchange pathways in the crystal and the observed magnetic structure is
entirely consistent with the predictions of ab initio calculations.
PMID- 28504801
TI - A Pt(0) complex with cyclic (alkyl)(amino)silylene and 1,3-divinyl-1,1,3,3
tetramethyldisiloxane ligands: synthesis, molecular structure, and catalytic
hydrosilylation activity.
AB - A platinum(0) complex bearing a cyclic (alkyl)(amino)silylene and a 1,3-divinyl
1,1,3,3-tetramethyldisiloxane (DVTMS) was synthesized and isolated in the form of
colorless crystals. The single-crystal X-ray diffraction analysis of this complex
in combination with theoretical calculations indicated that the Pt->Si pi-back
donation in this complex is weaker than that in the corresponding cyclic
dialkylsilylene-ligated Pt complex. The performance of this complex in the
catalytic hydrosilylation of (Me3SiO)2MeSi-H with various terminal alkenes that
contain functional groups was comparable to that of the corresponding cyclic
dialkylsilylene/DVTMS Pt(0) complex.
PMID- 28504802
TI - A temperature-resolved assembly of a series of the largest scandium-containing
polyoxotungstates.
AB - We report a temperature-resolved assembly of a series of novel nanoscale
hexameric Sc-containing polyoxometalates of {Sb6Sc11W60}, {Sb8Sc7W60}, and
{Sb8Sc6W60}. These compounds include the largest Sc-containing polyoxotungstates
and contain the largest number of Sc3+ ions of any polyoxotungstates reported to
date.
PMID- 28504805
TI - Monitoring of nanoparticle reactivity in solution: interaction of l-lysine and Ru
nanoparticles probed by chemical shift perturbation parallels regioselective H/D
exchange.
AB - Thanks to new water-soluble Ru nanoparticles (NPs) stabilized by sulfonated NHC
ligands, we demonstrate that it is possible to monitor the catalyst/substrate
interaction using NMR chemical shift perturbations (CSPs), under conditions that
closely resemble those applied during the enantiospecific C-H deuteration of l
lysine. Correlating the pH dependence of the interaction of l-lysine with the
surface of the RuNPs and its subsequent deuteration, our study underscores the
importance of oriented binding to the surface as a critical factor for H/D
exchange.
PMID- 28504807
TI - Occupational class and working beyond the retirement age: a cohort study.
AB - Objectives The aim of this study was to examine occupational class differences in
working more than six months beyond the mandatory retirement age and factors that
may contribute to these differences. Methods The study comprised a prospective
cohort study of a total of 5331 Finnish municipal employees (73% women) who were
not on work disability pension and reached the age eligible for old-age pension
in 2005-2011. Occupational class included four categories: managers and
professionals, lower grade non-manual, skilled manual, and elementary
occupations. Survey responses while at work were linked to national health and
pension registers. Results A total of 921 participants (17.3%) worked beyond the
pensionable age. Compared with elementary workers, skilled manual workers had a
similar probability [gender-adjusted risk ratio (RR) 0.95, 95% confidence
interval (95% CI) 0.72-1.23] while lower grade non-manual workers had a 2.03-fold
(95% CI 1.59-2.58), and managers and professionals had a 1.79-fold (95% CI 1.41
2.27) probability of working beyond the pensionable age. Adjustment for physical
workload (32.0% in lower non-manual, 36.7% in managers and professionals), work
time control (20.4% and 11.4%) and perceived work ability (16.5% and 29.1%)
contributed to the largest attenuation for these associations. Analyses using a
counterfactual approach suggested greater mediated effects for physical workload
and work time control than those observed in traditional mediation analyses.
Conclusions Employees with higher occupational classes are two times more likely
to continue working beyond the retirement age compared to those with lower
occupational classes. A large proportion of these differences were explained by
having physically light job, better work time control, and better self-rated work
ability among employees with high occupational class.
PMID- 28504808
TI - Outcome of Reverse Shoulder Arthroplasty for Patients With Parkinson's Disease: A
Matched Cohort Study.
AB - Parkinson's disease (PD) is a progressive neurologic disorder that affects the
musculoskeletal system. Currently, the use of reverse shoulder arthroplasty (RSA)
for patients with PD has not been adequately studied. The authors sought to
determine if RSA provided similar functional outcomes for patients with PD
compared with a matched cohort of patients without PD. Between 2004 and 2011, 10
patients with PD (4 men, 6 women) underwent RSA. Patients with PD were matched to
patients without PD at a 1:4 ratio based on age (average, 76 years; range, 63-85
years), sex (16 men, 24 women), preoperative diagnosis, and length of follow-up
(average, 43 months; range, 24-128 months). Outcome measures included range of
motion, visual analog scale (VAS) score, Simple Shoulder Test (SST) score,
American Shoulder and Elbow Society (ASES) score, and complication rates.
Patients with PD had improvements in SST scores, ASES total scores, and forward
flexion; however, they did not show statistically significant improvements in VAS
scores, ASES function scores, or other range of motion parameters. There was a
significant difference in postoperative functional outcome scores, SST scores,
and internal/external rotation between the 2 groups, but no difference in
postoperative pain scores, ASES total scores, forward flexion, or abduction.
Complications occurred in 4 of 10 patients with PD and 6 of 40 patients without
PD. Compared with the matched cohort, patients with PD achieved similar reduction
of pain but inferior clinical function following RSA. Improvement in range of
motion was less predictable and complication rates were significantly higher in
patients with PD. [Orthopedics. 2017; 40(4):e675-e680.].
PMID- 28504809
TI - Effect of Lymphedema Treatment for Management of Acute Pilon Fractures.
AB - Pilon fractures are high-energy injuries that often result in considerable edema
and compromise of the soft tissue envelope of the ankle. These injuries are
typically staged with an external fixator until the soft tissue is amenable for
definitive fixation. This study was conducted to determine the effects of
lymphedema treatment for the management of pilon fractures. Patients who
underwent open reduction and internal fixation of pilon fractures between 2007
and 2014 at the authors' level II trauma center were identified by Current
Procedural Terminology codes indicative of placement of an external fixator
(20690) and open reduction and internal fixation of a pilon fracture (27826,
27827, or 27828). The primary efficacy endpoint to determine negative outcomes
was 90 days after definitive fixation. Eighty-two patients with 84 pilon
fractures met inclusion criteria. Forty-eight ankles (57%) received lymphedema
treatment. There were no significant differences in population demographics
between the control and treatment groups. Median times to internal fixation in
the control and treatment groups were 20 days (inter-quartile range, 15.5-30
days) and 11 days (interquartile range, 6-18 days), respectively. This difference
was statistically significant (P=.001). Additionally, there was no significant
difference in the overall incidence of wound complications between the control
and treatment groups (P=.246). Compression wrapping for posttraumatic edema was
effective in reducing the time needed for soft tissues to be appropriate for
definitive surgical fixation of pilon fractures without increasing the risk of
wound complications. These promising results warrant future study. [Orthopedics.
2017; 40(4):e668-e674.].
PMID- 28504810
TI - Using a Structured Checklist to Improve the Orthopedic Ward Round: A Prospective
Cohort Study.
AB - Comprehensive and timely documentation on orthopedic ward rounds continues to be
problematic, leading to delayed or inappropriate patient care and
miscommunication between health care providers. The authors introduced a simple
checklist to improve the documentation on orthopedic ward rounds in their
institution. A prospective cohort study was performed. Standard care was provided
for cohort A. During a 2-week period, the documentation of patient care by
physicians following a ward round was assessed in terms of venous thromboembolism
prophylaxis, fasting status, wound or dressing plan, weight-bearing status, and
important surgical details. The physicians were blinded to this initial review.
For cohort B, a structured ward round checklist was introduced during a 2-week
period. A total of 132 patient encounters were recorded in cohort A. Important
issues that were rarely discussed included vital signs (11.4%), venous
thromboembolism prophylaxis (9.8%), and bowel status (3.8%). Issues that were
poorly documented included fasting status (9.1%), wound or dressing plan (6.8%),
and weight-bearing status (11.4%). After introduction of the checklist, daily
documentation of surgical details improved from 38.6% to 85.3% of patient
encounters. Fasting status documentation improved from 9.1% to 70.6% of patient
encounters. Venous thromboembolism prophylaxis discussion increased from 9.8% to
45.6% of the time, while its documentation improved from 6.8% to 92.6%.
Documentation of weight-bearing status improved from 11.4% to 83.8% (all
P<.0001). The use of a structured checklist during orthopedic ward rounds led to
significant improvement in both the consideration and the documentation of key
aspects of surgical care. [Orthopedics. 2017; 40(4):e663-e667.].
PMID- 28504811
TI - Percutaneous Screw Fixation for Scaphoid Fractures.
AB - Treatment of nondisplaced scaphoid waist fractures has evolved from conventional
cast immobilization to percutaneous screw insertion. This study assessed clinical
and radiologic outcomes of volar percutaneous screw fixation for 15 type B2
scaphoid fractures (according to the Herbert and Fisher classification). All
patients were followed for an average of 33 months (range, 6-50 months). All
fractures achieved radiographic union at an average of 57 days (range, 35-70
days), requiring no additional procedures. None of the patients showed
radiographic signs of osteoarthritis, osteonecrosis of the scaphoid, or hardware
related complications. For scaphoid waist fractures without collapse,
percutaneous screw fixation provided satisfactory results with a high rate of
union, early return of function, and minimal complications. [Orthopedics. 2017;
40(4):e729-e734.].
PMID- 28504812
TI - Overexpression of the YAP1 oncogene in clear cell renal cell carcinoma is
associated with poor outcome.
AB - Clear cell renal cell carcinoma (ccRCC) is the most common subtype of RCC (70
80%). Yes-associated protein 1 (YAP1) protein is a nuclear effector of the Hippo
pathway and acts as a transcriptional co-activator of genes involved in the
processes of growth and development of tissues. Hippo signaling, with its key
kinases, MST2 and large tumor suppressor kinase 1 (LATS1), plays a significant
role in the negative regulation of the amount and activity of YAP1 protein.
Components of the Hippo pathway and YAP1 levels are frequently dysregulated in a
variety of tumors, suggestive of their possible involvement in carcinogenesis.
Our aim was to evaluate gene and protein expression profiles of YAP1, MST2 and
LATS1 and the methylation status of MST2 and LATS1 promoters in ccRCC. mRNA
levels of MST2, LATS1 and YAP1 genes were assessed in the tumor and matched
normal kidney tissues of 86 patients, and in 12 samples of local metastases by
quantitative PCR (qPCR). Proteins were semi-quantified in 58 patient samples by
western blotting. Hypermethylation of LATS1 and MST2 promoters was measured by
methylation-specific high-resolution-melting qPCR. We found that LATS1 promoter
hypermethylation, decreased LATS1 mRNA/protein and increased YAP1 mRNA/protein
levels in tumor samples were associated with higher TNM and Fuhrman's stages and
patient survival. Higher YAP1 mRNA levels were associated with poor outcome
(HR=4.03, p=0.036). No changes in MST2 (promoter/mRNA/protein) were found. We
propose that deregulation of LATS1 and YAP1 expression is associated with ccRCC
progression and poor patient survival. Measurement of YAP1 mRNA levels in paired
tumor-normal kidney tissue samples may serve as a new prognostic factor in ccRCC.
PMID- 28504813
TI - Improved xenograft efficiency of esophageal adenocarcinoma cell lines through in
vivo selection.
AB - The present study aimed to investigate the orthotopic growth potential of two
generally available esophageal adenocarcinoma cell lines, OE33 and OACM5 1.C, and
a third in vivo selected subpopulation, OACM5 1.C SC1. One group of mice was
subcutaneously injected in the hind legs. Tumor growth was measured with
calipers. Another group was injected orthotopically in the distal esophageal wall
through median laparotomy. Tumor development was evaluated macroscopically and
confirmed microscopically. A subset of mice was evaluated with magnetic resonance
imaging (MRI) to follow tumor progression. Additionally, functional cell line
characteristics were evaluated in vitro (clonogenic, collagen invasion and sphere
formation assays, and protein analysis of cell-cell adhesion and cytoskeletal
proteins) to better understand xenograft behavior. OE33 cells were shown to be
epithelial-like, whereas OACM5 1.C and OACM5 1.C SC1 were more mesenchymal-like.
The three cell lines were non-invasive into native type I collagen gels. In vivo,
OE33 cells led to 63.6 and 100% tumor nodules after orthotopic (n=12) and
subcutaneous (n=8) injection, respectively. Adversely, OACM5 1.C cells did not
lead to tumor formation after orthotopic injection (n=6) and only 50% of
subcutaneous injections led to tumor nodules (n=8). However, the newly
established cell line OACM5 1.C SC1 resulted in 33% tumor formation when
orthotopically injected (n=6) and in 100% tumors when injected subcutaneously
(n=8). The higher xenograft rate of OACM5 1.C SC1 (P<0.05) corresponded with a
higher clonogenic potential compared to its parental cell line (P<0.0001). All
models showed local tumor growth without metastasis formation. In conclusion,
OACM5 1.C has a poor tumor take rate at an orthotopic and ectopic site. A
subpopulation obtained through in vivo selection, OACM5 1.C SC1, gives a
significant higher take rate, ectopically. Furthermore, OE33 establishes
orthotopic (and subcutaneous) xenografts in mice. These models can be of interest
for future studies, and their slow growth rates are a challenge for therapeutic
intervention.
PMID- 28504814
TI - MicroRNA-212 inhibits the metastasis of nasopharyngeal carcinoma by targeting
SOX4.
AB - MicroRNAs are important factors in the pathogenic processes of human types of
cancers including nasopharyngeal carcinoma (NPC). In the present study, we
confirmed that the microRNA-212 expression level was significantly decreased both
in NPC tissues and NPC cell lines. Decreased expression of miR-212 was associated
with advanced tumor-node-metastasis (TNM) stage and metastasis of NPC. Patients
with a lower level of miR-212 had significantly decreased rates of overall and
disease-free survival. Functional experiments showed that forced expression of
miR-212 inhibited the migration and invasion of NPC cells while inhibition of miR
212 increased the migration and invasion of NPC cells. Furthermore, the results
of luciferase assay, qRT-PCR and western blotting showed that SOX4 was the direct
downstream target of miR-212 in NPC cells. In addition, we further confirmed that
miR-212 exerted its inhibitory influence on the migration and invasion of NPC
cells by targeting SOX4.
PMID- 28504815
TI - The Arago Laboratory of Banyuls and some of its Academicians.
AB - Since its founding in 1881 by Henri de Lacaze-Duthiers (1821-1901), the Arago
Laboratory of Banyuls has been one of the three marine stations of the University
Pierre and Marie Curie-Paris 6. It is located in Banyuls (Banyuls-sur-Mer) in
Northern Catalonia. The center hosts researchers and students from all over the
world. Some became famous, including four Nobel Prize winners: Andre Lwoff
(1965), Pierre-Gilles de Gennes (1991), Albert Fert (2007) and Jules Hoffmann
(2011). This article focuses on five scientists closely related to the center.
The first three are Henri de Lacaze-Duthiers (1821-1901), the founder; Edouard
Chatton (1883-1947), eminent director of the center; and Andre Lwoff (1902-1994),
who before being known for his work in bacterial genetics and virology was an
outstanding protozoologist under the direction of Chatton. Lynn Margulis (1938
2011), a great friend of the Arago Laboratory and personal friend of the author,
is also remembered. Finally, there is a mention of Walter J. Gehring (1939-2014),
professor at the University of Basel, Switzerland. [Int Microbiol 19(4): 183-190
(2016)].
PMID- 28504816
TI - Virulence factors and antimicrobial resistance in environmental strains of Vibrio
alginolyticus.
AB - Vibrio alginolyticus has acquired increasing importance because this
microorganism may be pathogenic to aquatic animals and humans. It has been
reported that some V. alginolyticus strains carry virulence genes derived from
pathogenic V. cholerae and V. parahaemolyticus strains. In this work V.
alginolyticus was isolated from oyster samples acquired from a food-market in
Mexico City. Thirty isolates were identified as V. alginolitycus. Strains showed
beta-haemolysis and proteolytic activity and produced a capsule. Strains
displayed swimming and swarming motility and 93.3% of them produced siderophores.
Several genes encoding virulence factors were detected using PCR amplification.
These included proA, wza, vopD, vopB, hcp, vasH and vgrG genes, which were
present in all strains. Other genes had a variable representation: tdh (86.6%),
lafA (96.6%), pvsA (62%) and pvuA (16%). The trh gene could not be amplified from
any of the strains. The antimicrobial resistance profile revealed that more than
90% of the strains were resistant to beta-lactams antibiotics, 60% to cephalotin,
45% to amikacin, 16% to cephotaxime, and 10% to pefloxacin, while 100% were
susceptible to ceftriaxone. The V. alginolyticus strains isolated from oysters
showed multiple resistance to antibiotics and several virulence factors described
in well-characterized pathogenic vibrios. [Int Microbiol 19(4):191-198 (2016)].
PMID- 28504817
TI - Biofilm formation in catheter-related infections by Panton-Valentine leukocidin
producing Staphylococcus aureus.
AB - The use of invasive techniques, such as intravascular catheter insertion, and the
formation of biofilms in several devices by methicillin-resistant Staphylococcus
aureus (MRSA) have contributed to the increased number of septic patients,
morbidity and mortality. This study aimed to evaluate the virulence of strains
through catheter colonization and identification of microbial biofilm, as well as
pathological changes on the colonized skin. An experimental biofilm formation
model utilized catheter fragments implanted subcutaneously in 25 Swiss mice. The
technique consisted of inoculating a catheter fragment on the back of each
animal, followed by intradermal inoculation of 50 MUl of bacterial suspension at
1.0 * 107 colony forming units/ml. After 96 h, catheters were removed for
macroscopic analysis and evaluated through culture. Local skin fragments were
also extracted for histopathology analysis. Staphylococcus aureus can adhere to
catheters, colonize and form biofilms. The high amount of viable bacterial cells
colonizing catheters and virulence factors can lead to severe infections of skin
and adjacent tissues. [Int Microbiol 19(4): 199-207 (2016)].
PMID- 28504819
TI - Population-based cohort study of the effect of endometrial cancer classification
and treatment criteria on long-term survival.
AB - OBJECTIVE: To evaluate if increased individualization in endometrial cancer
classification/treatment affected relative survival. METHODS: The present
retrospective register-based population study included data from all women in the
western Swedish healthcare region who were treated for endometrial cancer between
January 1, 1995, and December 31, 2011. Outcomes and prognostic data were
retrieved from the western Swedish healthcare region's cancer and clinical
endometrial cancer registries. Patients were stratified based on two different
treatment programs (cohort 1 January 1, 1995, to September 10, 2006, and cohort 2
September 11, 2006, to December 31, 2011) and relative survival was compared.
RESULTS: Data from 4338 patients were included; 2936 in cohort 1 and 1402 in
cohort 2. Among endometrioid endometrial carcinomas, the 5-year relative survival
rate for did not differ significantly between the groups (P=0.751); radiotherapy
was used more frequently in cohort 1 (P<0.001). Among non-endometrioid
endometrial carcinomas, relative survival was lower in cohort 1 (P=0.006);
radiotherapy use was more frequent in cohort 1 and chemotherapy use was more
frequent in cohort 2 (P=0.001). CONCLUSION: Increased individualization in
endometrioid endometrial cancer management did not improve relative survival.
Improved relative survival was observed for non-endometrioid endometrial cancer;
possibly due to increased adjuvant chemotherapy use. This article is protected by
copyright. All rights reserved.
PMID- 28504818
TI - Characterization of Escherichia coli clinical isolates causing urinary tract
infections in the community of Chilpancingo, Mexico.
AB - Escherichia coli is the main cause of urinary tract infections (UTI) in
ambulatory patients, especially strains belonging to the B2 phylogenetic group
and ST131 clonal group. Antibiotic treatment is usually administered empirically;
however, it is not always effective due to bacterial multidrug resistance and the
production of extended spectrum beta-lactamases (ESBLs). The aim of this study
was to characterize E. coli clinical isolates from patients with UTI in a
community of the State of Guerrero, Mexico. From January to August 2014, 134
clinical isolates of E. coli were recovered. Strain identification and antibiotic
susceptibility were performed using the Vitek automated system. Phylogenetic and
O25b-ST13 groups were determined by multiple PCR. Identification of the blaCTX-M,
blaTEM, and blaSHV genes was performed by conventional PCR. We found that over
50% of the isolates were resistant to betalactams and quinolones, while 0 to 33%
were resistant to aminoglycosides and nitrofurans, and 56.49% of the strains were
ESBL producers. B2 phylogenetic group was the most predominant (43%) compared to
the other groups. The prevalence of bla genes was: blaCTX-M 64.3%, blaSHV 41.4%,
and blaTEM 54.3%. These results show a high percentage (55%) of multidrug
resistant strains isolated from UTI patients from the community in the city of
Chilpancingo, Guerrero, Mexico. [Int Microbiol 19(4): 209-215 (2016)].
PMID- 28504821
TI - Why you cannot transform your way out of trouble for small counts.
AB - While data transformation is a common strategy to satisfy linear modeling
assumptions, a theoretical result is used to show that transformation cannot
reasonably be expected to stabilize variances for small counts. Under broad
assumptions, as counts get smaller, it is shown that the variance becomes
proportional to the mean under monotonic transformations g(.) that satisfy
g(0)=0, excepting a few pathological cases. A suggested rule-of-thumb is that if
many predicted counts are less than one then data transformation cannot
reasonably be expected to stabilize variances, even for a well-chosen
transformation. This result has clear implications for the analysis of counts as
often implemented in the applied sciences, but particularly for multivariate
analysis in ecology. Multivariate discrete data are often collected in ecology,
typically with a large proportion of zeros, and it is currently widespread to use
methods of analysis that do not account for differences in variance across
observations nor across responses. Simulations demonstrate that failure to
account for the mean-variance relationship can have particularly severe
consequences in this context, and also in the univariate context if the sampling
design is unbalanced.
PMID- 28504823
TI - Centrifugal-driven, reduced-dimension, planar chromatography.
AB - A fundamental problem with efficiency in capillary action driven planar
chromatography results from diminishing flow rates as development proceeds,
giving rise to molecular diffusion related band dispersion for most sample types.
Overpressure and electrokinetic means to speed flow have been used successfully
in TLC. We explore the use of centrifugal force (CF) to drive flow for reduced
dimension planar platforms (ultra-TLC, low micrometer features, and nano-TLC,
nanoscale features). The silicon wafer platforms have two forms of continuous 2D
arrays created by either photolithography or metal dewetting followed by deep
reactive ion etching and coated with porous SiO2 . The flow pattern is unusual
with co-planar flows above and within the arrays. The effects of parameters such
as spin rate, solvent type, and surface character on flow rates is established
and can be substantially greater than capillary action flow. Using fluorescent
dyes, we investigate retardation factors and chromatographic plate height; the
latter falls in the low to sub-micrometer range. To the best of our knowledge, we
demonstrate the first analytical separations performed in pillar arrays using CF
to augment solvent flow.
PMID- 28504822
TI - Equilibrium, Kinetic and Structural Properties of Gallium(III) and Some Divalent
Metal Complexes Formed with the New DATAm and DATA5m Ligands.
AB - The development of 68 Ge/68 Ga generators has made the positron-emitting 68 Ga
isotope widely accessible and raised interest in new chelate complexes of Ga3+ .
The hexadentate 1,4-di(acetate)-6-methyl[amino(methyl)acetate]perhydro-1,4
diazepane (DATAm ) ligand and its bifunctional analogue, 1,4-di(acetate)-6
pentanoic acid[amino(methyl)acetate]perhydro-1,4-diazepane (DATA5m ), rapidly
form complexes with 68 Ga in high radiochemical yield. The stability constants of
DATAm and DATA5m complexes formed with Ga3+ , Zn2+ , Cu2+ , Mn2+ and Ca2+ have
been determined by using pH potentiometry, spectrophotometry (Cu2+ ) and 1 H and
71 Ga NMR spectroscopy (Ga3+ ). The stability constants of Ga(DATAm ) and
Ga(DATA5m ) complexes are slightly higher than those of Ga(AAZTA). The species
distribution calculations indicated the predominance of Ga(L)OH mixed-hydroxo
complexes at physiological pH. The 1 H and 71 Ga NMR spectroscopy studies
provided information about the coordinated functional groups of ligands and on
the kinetics of exchange between the Ga(L) and Ga(L)OH complexes. The
transmetalation reactions between the Ga(L) complexes and Cu2+ citrate (6=3 previous first trimester pregnancy losses with unexplained
etiology) and 131 non-RPL patients (no history of recurrent pregnancy loss). A
logistic regression model (LRM) was built and the model was externally validated
in another group of patients. RESULTS: The LRM included AA, DD, FDP, TT, APTT,
and PT. The overall accuracy of the LRM was 80.9%, with sensitivity and
specificity of 78.5% and 78.3%, respectively. The diagnostic threshold of the
possibility of the LRM was 0.6492, with a sensitivity of 78.5% and a specificity
of 78.3%. Subsequently, the LRM was validated with an overall accuracy of 83.6%.
CONCLUSION: The LRM is a valuable model for prediction of thrombophilia in URPL
patients.
PMID- 28504830
TI - Exploring Planar-Chiral Amino Siloxides.
AB - We present the synthesis, structure, and exemplary reactivity of siloxides with a
planar-chiral N,N-dimethylaminomethylferrocene backbone. Several zinc complexes
based on the racemic as well as the enantiomerically pure silanol were
synthesized in the presence of water and crystallographically characterized, and
their behavior in solution was examined. The chiral probe present in this system
is a valuable tool for identifying the structure in solution. Furthermore, the
zinc siloxides exhibit a comparable reactivity to the corresponding silanols.
Therefore, they can be regarded as "masked" silanols, especially when the
silanols are preparatively inaccessible.
PMID- 28504831
TI - From Discrete Molecular Cages to a Network of Cages Exhibiting Enhanced CO2
Adsorption Capacity.
AB - We have adopted the concept of "cage to frameworks" to successfully produce a Na
N connected coordination networked cage Na-NC1 by using a [3+6] porous imine
linked organic cage NC1 (Nanjing Cage 1) as the precursor. It is found that Na
NC1 exhibits hierarchical porosity (inherent permanent voids and interconnected
channel) and gas sorption measurements reveal a significantly enhanced CO2 uptake
(1093 cm3 g-1 at 23 bar and 273 K) than that of NC1 (162 cm3 g-1 under the same
conditions). In addition, Na-NC1 exhibits very low CO2 adsorption enthalpy making
it a good candidate for porous materials with both high CO2 storage and low
adsorption enthalpy.
PMID- 28504832
TI - Observation of Supramolecular Chirality in a Hierarchically Self-Assembled Mixed
Stack Charge-Transfer Complex.
AB - Supramolecular chirality was observed in a charge-transfer (CT) complex formed by
self-assembly of beta-cyclodextrin-linked pyrene and adamantane-linked
pyromellitic diimide in water. In the complex, the pyrene-pyromellitic diimide CT
interaction is reinforced several-fold by the strong beta-cyclodextrin-adamantane
inclusion binding interaction, as confirmed by 1 H NMR, absorption, fluorescence
and isothermal titration calorimetry studies. The CT complex exhibited high
stability, as inferred from the temperature-dependent absorption and NMR studies.
The CT absorption band exhibited a positive Cotton effect indicative of
supramolecular chirality for the complex. Twisted fibres were observed in TEM,
AFM, and SEM experiments. A mechanism involving synergistic binding interactions
leading to 2D sheets, followed by twisting of the sheet, is proposed for the
formation of twisted fibres. This system offers a chance to investigate a
combination of supramolecular CT and supramolecular chirality and explore their
synergistic effects.
PMID- 28504833
TI - The role of men in induced abortion decision making in an urban area of the
Philippines.
AB - OBJECTIVE: To understand beliefs about unintended pregnancy and abortion, and
perceptions about male roles related to pregnancy decision-making among men in
the Philippines. METHODS: Qualitative data were collected during in-depth
interviews and focus group discussions with men in an urban area of the
Philippines between October 2007 and July 2008. Interview participants were
purposively sampled from a local survey based on their having reported being
"afraid or troubled" or "afraid and planned to terminate" in response to a recent
pregnancy. Focus group participants were selected from the same communities. Data
were analyzed using the constant comparative method. RESULTS: In-depth interview
data from 15 men-each interviewed twice-and five focus group discussions were
included. Male interview participants reported feeling morally responsible for
the pregnancy and as wanting to avoid the "sin" of induced abortion; however,
they were concerned about being able to support a family financially.
Participants expressed resentment towards partners who attempted or completed an
induced abortion without their knowledge. In such cases, men would disparage
their partner and cease interacting with them to avoid the "sin" of induced
abortion. CONCLUSION: Participants described negative feelings towards women
seeking induced abortions, and their own desire to avoid associated "sin". This
highlights the effects of unintended pregnancy and induced abortion on young
Filipino men, including their own experience of abortion stigma.
PMID- 28504834
TI - Resource stoichiometry and availability modulate species richness and biomass of
tropical litter macro-invertebrates.
AB - High biodiversity and biomass of soil communities are crucial for litter
decomposition in terrestrial ecosystems such as tropical forests. However, the
leaf litter that these communities consume is of particularly poor quality as
indicated by elemental stoichiometry. The impact of resource quantity, quality
and other habitat parameters on species richness and biomass of consumer
communities is often studied in isolation, although much can be learned from
simultaneously studying both community characteristics. Using a dataset of 780
macro-invertebrate consumer species across 32 sites in tropical lowland rain
forest and agricultural systems on Sumatra, Indonesia, we investigated the
effects of basal resource stoichiometry (C:X ratios of N, P, K, Ca, Mg, Na, S in
local leaf litter), litter mass (basal resource quantity and habitat space),
plant species richness (surrogate for litter habitat heterogeneity), and soil pH
(acidity) on consumer species richness and biomass across different consumer
groups (i.e. 3 feeding guilds and 10 selected taxonomic groups). In order to
distinguish the most important predictors of consumer species richness and
biomass, we applied a standardised model averaging approach investigating the
effects of basal resource stoichiometry, litter mass, plant species richness and
soil pH on both consumer community characteristics. This standardised approach
enabled us to identify differences and similarities in the magnitude and
importance of such effects on consumer species richness and biomass. Across
consumer groups, we found litter mass to be the most important predictor of both
species richness and biomass. Resource stoichiometry had a more pronounced impact
on consumer species richness than on their biomass. As expected, taxonomic groups
differed in which resource and habitat parameters (basal resource stoichiometry,
litter mass, plant species richness and pH) were most important for modulating
their community characteristics. The importance of litter mass for both species
richness and biomass indicates that these tropical consumers strongly depend on
habitat space and resource availability. Our study supports previous theoretical
work indicating that consumer species richness is jointly influenced by resource
availability and the balanced supply of multiple chemical elements in their
resources.
PMID- 28504835
TI - Electronic and Ligand Properties of Skeletally Substituted Cyclic
(Alkyl)(Amino)Carbenes (CAACs) and Their Reactivity towards Small Molecule
Activation: A Theoretical Study.
AB - Quantum chemical calculations have been carried out to understand the ligand
properties of skeletally modified cyclic alkyl amino carbenes. The stability of
these carbenes has been assessed from an evaluation of their singlet-triplet and
stabilization energy values. Ylide substituted carbenes are found to be more
stable than non-ylidic ones in their optimized singlet state. Nucleophilicity and
electrophilicity indices values were evaluated in order to further investigate
the reactivity of these carbenes. The calculated values of proton affinities and
the degree of gallium pyramidalization in the carbene-GaCl3 adducts correlate
well with the sigma-basicity of these carbenes. The reactivity of non-ylidic
carbenes toward the activation of both H2 and NH3 are calculated to be more
favourable compared to that of parent CAAC. On the other hand, ylide anchored
carbenes are found to be unsuccessful toward the activation of both H2 and NH3 .
PMID- 28504836
TI - Simple and fast overidentified rank estimation for right-censored length-biased
data and backward recurrence time.
AB - Length-biased survival data subject to right-censoring are often collected from a
prevalent cohort. However, informative right censoring induced by the sampling
design creates challenges in methodological development. While certain
conditioning arguments could circumvent the problem of informative censoring,
related rank estimation methods are typically inefficient because the marginal
likelihood of the backward recurrence time is not ancillary. Under a
semiparametric accelerated failure time model, an overidentified set of log-rank
estimating equations is constructed based on the left-truncated right-censored
data and backward recurrence time. Efficient combination of the estimating
equations is simplified by exploiting an asymptotic independence property between
two sets of estimating equations. A fast algorithm is studied for solving non
smooth, non-monotone estimating equations. Simulation studies confirm that the
overidentified rank estimator can have a substantially improved estimation
efficiency compared to just-identified rank estimators. The proposed method is
applied to a dementia study for illustration.
PMID- 28504837
TI - Immunotherapy for metastatic renal cell carcinoma.
AB - BACKGROUND: Since the mid-2000s, the field of metastatic renal cell carcinoma
(mRCC) has experienced a paradigm shift from non-specific therapy with broad
acting cytokines to specific regimens, which directly target the cancer, the
tumour microenvironment, or both.Current guidelines recommend targeted therapies
with agents such as sunitinib, pazopanib or temsirolimus (for people with poor
prognosis) as the standard of care for first-line treatment of people with mRCC
and mention non-specific cytokines as an alternative option for selected
patients.In November 2015, nivolumab, a checkpoint inhibitor directed against
programmed death-1 (PD-1), was approved as the first specific immunotherapeutic
agent as second-line therapy in previously treated mRCC patients. OBJECTIVES: To
assess the effects of immunotherapies either alone or in combination with
standard targeted therapies for the treatment of metastatic renal cell carcinoma
and their efficacy to maximize patient benefit. SEARCH METHODS: We searched the
Cochrane Library, MEDLINE (Ovid), Embase (Ovid), ISI Web of Science and registers
of ongoing clinical trials in November 2016 without language restrictions. We
scanned reference lists and contacted experts in the field to obtain further
information. SELECTION CRITERIA: We included randomized controlled trials (RCTs)
and quasi-RCTs with or without blinding involving people with mRCC. DATA
COLLECTION AND ANALYSIS: We collected and analyzed studies according to the
published protocol. Summary statistics for the primary endpoints were risk ratios
(RRs) and mean differences (MD) with their 95% confidence intervals (CIs). We
rated the quality of evidence using GRADE methodology and summarized the quality
and magnitude of relative and absolute effects for each primary outcome in our
'Summary of findings' tables. MAIN RESULTS: We identified eight studies with 4732
eligible participants and an additional 13 ongoing studies. We categorized
studies into comparisons, all against standard therapy accordingly as first-line
(five comparisons) or second-line therapy (one comparison) for mRCC.Interferon
(IFN)-alpha monotherapy probably increases one-year overall mortality compared to
standard targeted therapies with temsirolimus or sunitinib (RR 1.30, 95% CI 1.13
to 1.51; 2 studies; 1166 participants; moderate-quality evidence), may lead to
similar quality of life (QoL) (e.g. MD -5.58 points, 95% CI -7.25 to -3.91 for
Functional Assessment of Cancer - General (FACT-G); 1 study; 730 participants;
low-quality evidence) and may slightly increase the incidence of adverse events
(AEs) grade 3 or greater (RR 1.17, 95% CI 1.03 to 1.32; 1 study; 408
participants; low-quality evidence).There is probably no difference between IFN
alpha plus temsirolimus and temsirolimus alone for one-year overall mortality (RR
1.13, 95% CI 0.95 to 1.34; 1 study; 419 participants; moderate-quality evidence),
but the incidence of AEs of 3 or greater may be increased (RR 1.30, 95% CI 1.17
to 1.45; 1 study; 416 participants; low-quality evidence). There was no
information on QoL.IFN-alpha alone may slightly increase one-year overall
mortality compared to IFN-alpha plus bevacizumab (RR 1.17, 95% CI 1.00 to 1.36; 2
studies; 1381 participants; low-quality evidence). This effect is probably
accompanied by a lower incidence of AEs of grade 3 or greater (RR 0.77, 95% CI
0.71 to 0.84; 2 studies; 1350 participants; moderate-quality evidence). QoL could
not be evaluated due to insufficient data.Treatment with IFN-alpha plus
bevacizumab or standard targeted therapy (sunitinib) may lead to similar one-year
overall mortality (RR 0.37, 95% CI 0.13 to 1.08; 1 study; 83 participants; low
quality evidence) and AEs of grade 3 or greater (RR 1.18, 95% CI 0.85 to 1.62; 1
study; 82 participants; low-quality evidence). QoL could not be evaluated due to
insufficient data.Treatment with vaccines (e.g. MVA-5T4 or IMA901) or standard
therapy may lead to similar one-year overall mortality (RR 1.10, 95% CI 0.91 to
1.32; low-quality evidence) and AEs of grade 3 or greater (RR 1.16, 95% CI 0.97
to 1.39; 2 studies; 1065 participants; low-quality evidence). QoL could not be
evaluated due to insufficient data.In previously treated patients, targeted
immunotherapy (nivolumab) probably reduces one-year overall mortality compared to
standard targeted therapy with everolimus (RR 0.70, 95% CI 0.56 to 0.87; 1 study;
821 participants; moderate-quality evidence), probably improves QoL (e.g. RR
1.51, 95% CI 1.28 to 1.78 for clinically relevant improvement of the FACT-Kidney
Symptom Index Disease Related Symptoms (FKSI-DRS); 1 study, 704 participants;
moderate-quality evidence) and probably reduces the incidence of AEs grade 3 or
greater (RR 0.51, 95% CI 0.40 to 0.65; 1 study; 803 participants; moderate
quality evidence). AUTHORS' CONCLUSIONS: Evidence of moderate quality
demonstrates that IFN-alpha monotherapy increases mortality compared to standard
targeted therapies alone, whereas there is no difference if IFN is combined with
standard targeted therapies. Evidence of low quality demonstrates that QoL is
worse with IFN alone and that severe AEs are increased with IFN alone or in
combination. There is low-quality evidence that IFN-alpha alone increases
mortality but moderate-quality evidence on decreased AEs compared to IFN-alpha
plus bevacizumab. Low-quality evidence shows no difference for IFN-alpha plus
bevacizumab compared to sunitinib with respect to mortality and severe AEs. Low
quality evidence demonstrates no difference of vaccine treatment compared to
standard targeted therapies in mortality and AEs, whereas there is moderate
quality evidence that targeted immunotherapies reduce mortality and AEs and
improve QoL.
PMID- 28504840
TI - Clinical utility of a short resting-state MRI scan in differentiating bipolar
from unipolar depression.
AB - OBJECTIVE: Depression in bipolar disorder (BipD) requires a therapeutic approach
that is from treating unipolar major depressive disorder (UniD), but to date, no
reliable methods could separate these two disorders. The aim of this study was to
establish the clinical validity and utility of a non-invasive functional MRI
based method to classify BipD from UniD. METHOD: The degree of connectivity
(degree centrality or DC) of every small unit (voxel) with every other unit of
the brain was estimated in 22 patients with BipD and 22 age, gender, and
depressive severity-matched patients with UniD and 22 healthy controls. Pattern
classification analysis was carried out using a support-vector machine (SVM)
approach. RESULTS: Degree centrality pattern from 8-min resting fMRI
discriminated BipD from UniD with an accuracy of 86% and diagnostic odds ratio of
9.6. DC was reduced in the left insula and increased in bilateral precuneus in
BipD when compared to UniD. In this sample with a high degree of uncertainty (50%
prior probability), positive predictive value of the DC test was 79%. CONCLUSION:
Degree centrality maps are potential candidate measures to separate bipolar
depression from unipolar depression. Test performance reported here requires
further pragmatic evaluation in regular clinical practice.
PMID- 28504839
TI - The pathological Trento variant of alpha-1-antitrypsin (E75V) shows nonclassical
behaviour during polymerization.
AB - Severe alpha-1-antitrypsin deficiency (AATD) is most frequently associated with
the alpha-1-antitrypsin (AAT) Z variant (E342K). ZZ homozygotes exhibit
accumulation of AAT as polymers in the endoplasmic reticulum of hepatocytes. This
protein deposition can lead to liver disease, with the resulting low circulating
levels of AAT predisposing to early-onset emphysema due to dysregulation of
elastinolytic activity in the lungs. An increasing number of rare AAT alleles
have been identified in patients with severe AATD, typically in combination with
the Z allele. Here we report a new mutation (E75V) in a patient with severe
plasma deficiency, which we designate Trento. In contrast to the Z mutant, Trento
AAT was secreted efficiently when expressed in cellular models but showed
compromised conformational stability. Polyacrylamide gel electrophoresis (PAGE)
and ELISA-based analyses of the secreted protein revealed the presence of
oligomeric species with electrophoretic and immunorecognition profiles different
from those of Z and S (E264V) AAT polymers, including reduced recognition by
conformational monoclonal antibodies 2C1 and 4B12. This altered recognition was
not due to direct effects on the epitope of the 2C1 monoclonal antibody which we
localized between helices E and F. Structural analyses indicate the likely basis
for polymer formation is the loss of a highly conserved stabilizing interaction
between helix C and the posthelix I loop. These results highlight this region as
important for maintaining native state stability and, when compromised, results
in the formation of pathological polymers that are different from those produced
by Z and S AAT.
PMID- 28504841
TI - Chemical Composition, Antibacterial, Schistosomicidal, and Cytotoxic Activities
of the Essential Oil of Dysphania ambrosioides (L.) Mosyakin & Clemants
(Chenopodiaceae).
AB - We have investigated the chemical composition and the antibacterial activity of
the essential oil of Dysphania ambrosioides (L.) Mosyakin & Clemants
(Chenopodiaceae) (DA-EO) against a representative panel of cariogenic bacteria.
We have also assessed the in vitro schistosomicidal effects of DA-EO on
Schistosoma mansoni and its cytotoxicity to GM07492-A cells in vitro. Gas
chromatography (GC) and gas chromatography-mass spectrometry (GC/MS) revealed
that the monoterpenes cis-piperitone oxide (35.2%), p-cymene (14.5%),
isoascaridole (14.1%), and alpha-terpinene (11.6%) were identified by as the
major constituents of DA-EO. DA-EO displayed weak activity against Streptococcus
sobrinus and Enterococcus faecalis (minimum inhibitory concentration (MIC) = 1000
MUg/ml). On the other hand, DA-EO at 25 and 12.5 MUg/ml presented remarkable
schistosomicidal action in vitro and killed 100% of adult worm pairs within 24
and 72 h, respectively. The LC50 values of DA-EO were 6.50 +/- 0.38, 3.66 +/-
1.06, and 3.65 +/- 0.76 MUg/ml at 24, 48, and 72 h, respectively. However, DA-EO
at concentrations higher than 312.5 MUg/ml significantly reduced the viability of
GM07492-A cells (IC50 = 207.1 +/- 4.4 MUg/ml). The selectivity index showed that
DA-EO was 31.8 times more toxic to the adult S. mansoni worms than GM07492-A
cells. Taken together, these results demonstrate the promising schistosomicidal
potential of the essential oil of Dysphania ambrosioides.
PMID- 28504838
TI - Human innate lymphoid cells (ILCs) in filarial infections.
AB - Filarial infections are characteristically chronic and can cause debilitating
diseases governed by parasite-induced innate and adaptive immune responses.
Filarial parasites traverse or establish niches in the skin (migrating infective
larvae), in nonmucosal tissues (adult parasite niche) and in the blood or skin
(circulating microfilariae) where they intersect with the host immune response.
While several studies have demonstrated that filarial parasites and their
antigens can modulate myeloid cells (monocyte, macrophage and dendritic cell
subsets), T- and B-lymphocytes and skin resident cell populations, the role of
innate lymphoid cells during filarial infections has only recently emerged.
Despite the identification and characterization of innate lymphoid cells (ILCs)
in murine helminth infections, little is actually known about the role of human
ILCs during parasitic infections. The focus of this review will be to highlight
the composition of ILCs in the skin, lymphatics and blood; where the host
parasite interaction is well-defined and to examine the role of ILCs during
filarial infections.
PMID- 28504844
TI - Naphthalimide-Based Polyammonium Chemosensors for Anions: Study of Binding
Properties and Sensing Mechanisms.
AB - New naphthalimide-based receptors for anions have been synthesized. Efficient
synthetic routes have been discovered to functionalize the naphthalimide core
with branched polyamines. Binding and sensing properties of the receptors were
studied by potentiometric, NMR and fluorescence titrations. The receptors bind
selectively to the pyrophosphate anion in buffered aqueous solutions. The
receptors with more than six amine groups in the structure demonstrated the
highest affinities for pyrophosphate. The fluorescence response towards anions
was found to be dependent on the position of the amine groups relative to the
naphthalimide core, and on the pH of the buffered solution. Three sensing
mechanisms have been found that explain fluorescence responses of receptors
towards anions in an aqueous solution.
PMID- 28504843
TI - A novel synthetic chemical entity (UPEI-800) is neuroprotective in vitro and in
an in vivo rat model of oxidative stress.
AB - In this study, we tested a novel synthetic pyrazole-containing compound, 5-amino
1-phenyl-1H-pyrazole-4-carbonitrile (APPC), as an antioxidant in both in vitro
and in vivo models of oxidative stress. In addition, the utility of covalently
combining APPC with another well-established antioxidant, lipoic acid (LA), was
also tested in both models. The in vitro results demonstrated that pretreatment
with APPC in a mixed neuronal-glial culture exposed to oxygen-glucose deprivation
(OGD) followed by reoxygenation-refeeding, resulted in significant
neuroprotection at concentrations between 2.5 to 25 MUmol/L. In contrast, LA was
not neuroprotective following OGD alone or following reoxygenation-refeeding.
However, the synthetic covalent combination of APPC with LA, named "UPEI-800",
resulted in significant neuroprotection at concentrations between 0.027 and 2.7
MUmol/L (100-fold more potent than APPC alone), an effect shown to be correlated
with increased cellular antioxidant capacity. Further, in an in vivo model of
ischaemia-reperfusion injury following transient occlusion of the middle cerebral
artery (tMCAO), both APPC (0.1 and 1.0 mg/kg) and UPEI-800 (1*10-3 mg/kg)
provided significant neuroprotection. Consistent with the in vitro findings, the
in vivo results following tMCAO also demonstrated a 100-fold increase in the
potency of the covalently linked compound UPEI-800 compared to APPC alone.
PMID- 28504842
TI - Safety and efficacy of current direct-acting antiviral regimens in kidney and
liver transplant recipients with hepatitis C: Results from the HCV-TARGET study.
AB - : Data outside of clinical trials with direct-acting antiviral regimens with or
without ribavirin as treatment of chronic hepatitis C virus in solid organ
transplant recipients are limited. Liver transplant (LT), kidney transplant (KT),
and dual liver kidney (DLK) transplant recipients from the Hepatitis C
Therapeutic Registry and Research Network database, a multicenter, longitudinal
clinical care treatment cohort, treated with direct-acting antiviral regimens
between January 1, 2014, and February 15, 2016, were included to assess safety
and efficacy. Included were 443 posttransplant patients (KT = 60, LT = 347, DLK =
36); 42% had cirrhosis, and 54% had failed prior antiviral therapy. Most had
genotype (GT) 1 (87% with 52% GT1a, 27% GT1b, and 8% GT1 no subtype) and were
treated with sofosbuvir (SOF)/ledipasvir +/- ribavirin (85%) followed by SOF +
daclatasvir +/- ribavirin (9%) and ombitasvir/paritaprevir/ritonavir + dasabuvir
+/- ribavirin (6%). Rates of sustained virologic response (SVR) at 12 weeks were
available on 412 patients, and 395 patients (95.9%) achieved SVR at 12 weeks:
96.6%, 94.5%, and 90.9% among LT, KT, and DLK transplant recipients,
respectively. Ribavirin did not influence SVR rates and was more often used in
those with higher BMI, higher estimated glomerular filtration rate and lower
creatinine. Female gender, baseline albumin >=3.5 g/dL, baseline total bilirubin
<=1.2 mg/dL, absence of cirrhosis, and hepatic decompensation predicted SVR at 12
weeks. Six episodes of acute rejection (n = 2 KT, 4 LT) occurred, during
hepatitis C virus treatment in 4 and after cessation of treatment in 2.
CONCLUSION: In a large prospective observational cohort study, direct-acting
antiviral therapy with SOF/ledipasvir, ombitasvir/paritaprevir/ritonavir +
dasabuvir, and SOF plus daclatasvir was efficacious and safe in LT, KT, and DLK
transplant recipients; ribavirin did not influence SVR, and graft rejection was
rare. (Hepatology 2017;66:1090-1101).
PMID- 28504845
TI - Rhodium(I)-Catalyzed Tertiary Phosphine Directed C-H Arylation: Rapid
Construction of Ligand Libraries.
AB - Modification of commercially available monophosphine ligands with either aryl
bromides or chlorides by rhodium(I)-catalyzed, tertiary phosphine directed C-H
activation is described. A series of ligand libraries containing mono- and diaryl
substituted groups, having different steric and electronic properties, were
obtained in high yields. Based on the outstanding properties of their parent
scaffolds, the modified ligands have been found to be powerful in organic
reactions.
PMID- 28504847
TI - Implementation of a digital preparation validation tool in dental skills
laboratory training.
AB - AIM: To describe the implementation of a digital tool for preparation validation
and evaluate it as an aid in students' self-assessment. METHODS: Students at the
final semester of skills laboratory training were asked to use a digital
preparation validation tool (PVT) when performing two different tasks;
preparation of crowns for teeth 11 and 21. The students were divided into two
groups. Group A self-assessed and scanned all three attempts at 21 ("prep-and
scan"). Group B self-assessed all attempts chose the best one and scanned it
("best-of-three"). The situation was reversed for 11. The students assessed five
parameters of the preparation and marked them as approved (A) or failed (F).
These marks were compared with the information from the PVT. The students also
completed a questionnaire. Each question was rated from 1 to 5. Teachers'
opinions were collected at staff meetings throughout the project. RESULTS: Most
students in the "prep-and-scan" groups showed an increase in agreement between
their self-assessment and the information from the PVT, whereas students in the
"best-of-three" groups showed lower levels of agreement. All students rated the
PVT positively. Most strongly agreed that the tool was helpful in developing
skills (mean 4.15), easy to use (mean 4.23) and that it added benefits in
comparison to existing assessment tools (mean 4.05). They did not however, fully
agree that the tool is time efficient (mean 2.55), and they did not consider it a
substitute for verbal teacher feedback. Teachers' feedback suggested advantages
of the tool in the form of ease of use, visual aid and increasing interest and
motivation during skills laboratory training however, they did not notice a
reduction in need of verbal feedback. CONCLUSIONS: Within the limitations of the
study, our conclusion is that a digital PVT may be a valuable adjunct to other
assessment tools in skills laboratory training.
PMID- 28504846
TI - Adverse event management in patients with relapsed and refractory multiple
myeloma taking pomalidomide plus low-dose dexamethasone: A pooled analysis.
AB - OBJECTIVES: Heavily pretreated patients with relapsed and refractory multiple
myeloma are susceptible to treatment-related adverse events (AEs). Managing AEs
are important to ensure patients continue therapy long enough to receive the best
clinical benefit. Data from the MM-002, MM-003, and MM-010 trials were pooled to
further characterize the safety profile of pomalidomide plus low-dose
dexamethasone and AE management. METHODS: This analysis included 1088 patients
who received >= 2 prior therapies, including lenalidomide and bortezomib, and
progressed <= 60 days of last therapy. Patients received 28-day cycles of
pomalidomide 4 mg/day on days 1-21 and low-dose dexamethasone 40 mg (20 mg if
aged > 75 years) weekly until disease progression or unacceptable toxicity.
Thromboprophylaxis was required. RESULTS: The most common grade 3/4 AEs were
neutropenia (56.2%), anemia (32.3%), and thrombocytopenia (25.8%), which occurred
within the first few cycles of treatment. Grade 3/4 infections occurred in 33.7%
patients, of whom 13.9% had pneumonia, and 40.3% had neutropenia. Pomalidomide
dose reductions or interruptions were reported in 24.2% and 66.0% of patients,
respectively. AEs were managed by dose modifications and/or supportive care.
CONCLUSIONS: Pomalidomide plus low-dose dexamethasone showed an acceptable safety
profile, and AEs were well managed according to study protocols and established
guidelines.
PMID- 28504848
TI - Association of traumatic head injuries and maxillofacial fractures: A
retrospective study.
AB - BACKGROUND/AIMS: The association of traumatic head injury (THI) with
maxillofacial fractures (MFF) is a major health concern worldwide. In spite of
the close anatomical proximity of maxillofacial bones to the cranium, the
association of THI with MFF is controversial. The aim of this study was to assess
the association between THI and MFF. Other factors associated with THI in
patients with MFF were also investigated. MATERIALS AND METHODS: A hospital-based
retrospective study was conducted at the OMFS Unit, Hospital USM, Kelantan,
Malaysia. From 12 June 2013 to 31 December 2015, 473 patient records with MFF
were reviewed to evaluate the association of THI and MFF. RESULTS: A total of 331
patients (69.98%) presented with concomitant THI. The most common associated THI
were cranial bone fractures (68.6%) followed by intracranial injuries and
concussion. A significant association existed between the Glasgow coma scale
(GCS) score and the presence of THI concomitant MFF with P-value <.001. The
univariable logistic regression analysis revealed that age group (31-40 years),
cause of injury (road traffic accident-RTA), all midface fracture types and most
of the mandibular fracture types were statistically associated with the presence
of THI. The multivariable logistic regression analysis revealed that the cause of
the injury (RTA) and MFF types (nasal bone, zygomatic complex, zygomatic arch,
orbital wall, maxillary sinus wall and the alveolar process of mandible
fractures) were statistically significantly associated with THI in patients with
MFF. CONCLUSION: There was a high prevalence of THI among patients with MFF
(69.98%). RTA, nasal bone, zygomatic complex, zygomatic arch, orbital wall,
maxillary sinus wall and mandibular alveolar process fractures were significantly
associated with THI in patients who sustained a MFF.
PMID- 28504849
TI - Diagnosis and treatment of cervical papillary squamous cell carcinoma with
unknown depth of stromal invasion.
AB - OBJECTIVE: To evaluate the diagnosis and treatment of papillary squamous cell
carcinoma (PSCC) of the uterine cervix with unknown depth of stromal invasion.
METHODS: In a retrospective study, the diagnostic and treatment strategies after
colposcopy-guided biopsy sampling were assessed among patients seen at a
university hospital in Shanghai, China, in 2008-2015. RESULTS: Among 55 patients,
29 with clinically visible lesions underwent radical hysterectomy; the final
pathologic diagnosis was invasive squamous cell carcinoma in all patients. Of
these patients, eight had undergone loop electrosurgical excision procedure
(LEEP) and two had undergone a second biopsy sampling before radical hysterectomy
was performed. Of the 26 patients with no clinically visible lesions, 17 had
cervical lesions as confirmed by medical imaging and 12 of these patients
underwent LEEP. The pathologic examination showed lesions of varying severity but
no cancer in situ. The remaining five patients underwent radical hysterectomy;
one of these patients was found to have micro-invasive cancer. CONCLUSION:
Patients with PSCC with unknown depth of stromal invasion and clinically visible
lesions receive radical hysterectomy rather than undergoing a second biopsy
sampling or LEEP. Less invasive surgery is recommended for patients with no
clinically visible lesions.
PMID- 28504851
TI - Identification of bacterial guanylate cyclases.
PMID- 28504850
TI - Visualizing Biological Copper Storage: The Importance of Thiolate-Coordinated
Tetranuclear Clusters.
AB - Bacteria possess cytosolic proteins (Csp3s) capable of binding large quantities
of copper and preventing toxicity. Crystal structures of a Csp3 plus increasing
amounts of CuI provide atomic-level information about how a storage protein loads
with metal ions. Many more sites are occupied than CuI equiv added, with binding
by twelve central sites dominating. These can form [Cu4 (S-Cys)4 ] intermediates
leading to [Cu4 (S-Cys)5 ]- , [Cu4 (S-Cys)6 ]2- , and [Cu4 (S-Cys)5 (O-Asn)]-
clusters. Construction of the five CuI sites at the opening of the bundle lags
behind the main core, and the two least accessible sites at the opposite end of
the bundle are occupied last. Facile CuI cluster formation, reminiscent of that
for inorganic complexes with organothiolate ligands, is largely avoided in
biology but is used by proteins that store copper in the cytosol of prokaryotes
and eukaryotes, where this reactivity is also key to toxicity.
PMID- 28504852
TI - Highly Ordered Self-Assembly of Native Proteins into 1D, 2D, and 3D Structures
Modulated by the Tether Length of Assembly-Inducing Ligands.
AB - In nature, proteins self-assemble into various structures with different
dimensions. To construct these nanostructures in laboratories, normally proteins
with different symmetries are selected. However, most of these approaches are
engineering-intensive and highly dependent on the accuracy of the protein design.
Herein, we report that a simple native protein LecA assembles into one
dimensional nanoribbons and nanowires, two-dimensional nanosheets, and three
dimensional layered structures controlled mainly by small-molecule assembly
inducing ligands RnG (n=1, 2, 3, 4, 5) with varying numbers of ethylene oxide
repeating units. To understand the formation mechanism of the different
morphologies controlled by the small-molecule structure, molecular simulations
were performed from microscopic and mesoscopic view, which presented a clear
relationship between the molecular structure of the ligands and the assembled
patterns. These results introduce an easy strategy to control the assembly
structure and dimension, which could shed light on controlled protein assembly.
PMID- 28504853
TI - Deriving ICD-11 personality disorder domains from dsm-5 traits: initial attempt
to harmonize two diagnostic systems.
AB - OBJECTIVE: The personality disorder domains proposed for the ICD-11 comprise
Negative Affectivity, Detachment, Dissociality, Disinhibition, and Anankastia,
which are reasonably concordant with the higher-order trait domains in the
Alternative DSM-5 Model for Personality Disorders. METHOD: We examined (i)
whether designated DSM-5 trait facets can be used to describe the proposed ICD-11
trait domains, and (ii) how these ICD-11 trait features are hierarchically
organized. A mixed Danish derivation sample (N = 1541) of 615 psychiatric out
patients and 925 community participants along with a US replication sample (N =
637) completed the Personality Inventory for DSM-5 (PID-5). Sixteen PID-5 traits
were designated to cover features of the ICD-11 trait domains. RESULTS:
Exploratory structural equation modeling (ESEM) analyzes showed that the
designated traits were meaningfully organized in the proposed ICD-11 five-domain
structure as well as other recognizable higher-order models of personality and
psychopathology. Model fits revealed that the five proposed ICD-11 personality
disorder domains were satisfactorily resembled, and replicated in the independent
US sample. CONCLUSION: The proposed ICD-11 personality disorder domains can be
accurately described using designated traits from the DSM-5 personality trait
system. A scoring algorithm for the ICD-11 personality disorder domains is
provided in appendix.
PMID- 28504855
TI - Relationships between digit ratio (2D:4D) and basketball performance in
Australian men.
AB - OBJECTIVE: To investigate relationships between the digit ratio (2D:4D) and
competitive basketball performance in Australian men. METHODS: Using an
observational cross-sectional design a total of 221 Australian basketball players
who competed in the Olympic Games, International Basketball Federation World
Championships/Cup, Australian National Basketball League, Central Australian
Basketball League or socially had their 2D:4Ds measured. Analysis of variance was
used to assess differences in mean 2D:4Ds between men playing at different
competitive standards, with relationships between 2D:4Ds and basketball game
related statistics assessed using Pearson's product moment correlations in men
playing at a single competitive standard. RESULTS: There were significant
differences between competitive standards for the left 2D:4D following Bonferroni
correction, but not for the right 2D:4D, with basketballers who achieved higher
competitive standards tending to have lower left 2D:4Ds. No important
correlations between 2D:4D and basketball game-related statistics were found,
with correlations typically negligible. CONCLUSIONS: This study indicated that
the 2D:4D can discriminate between basketballers competing at different
standards, but not between basketballers within a single competitive standard
using objective game-related statistics.
PMID- 28504854
TI - The risk of early occurrence and recurrence of hepatocellular carcinoma in
hepatitis C-infected patients treated with direct-acting antivirals with and
without pegylated interferon: A Belgian experience.
AB - Recently, concerns were raised of high rates of HCC recurrence in patients
treated with direct-acting antivirals (DAA) for hepatitis C infection. We
investigated the HCC occurrence and recurrence rates within 6 months after
treatment with DAA with or without pegylated interferon (PEG-IFN) in real life.
This is a retrospective, multicenter cohort trial, executed in 15 hospitals
distributed across Belgium. Populations were matched based on fibrosis score
(Metavir F3-F4). Patients with a Child-Pugh score >= B were excluded. In total,
567 patients were included, of whom 77 were treated with PEG-IFN+DAA between 2008
and 2013 and 490 with DAA without PEG-IFN between 2013 and 2015. Patients treated
with PEG-IFN+DAA (53+/-9y) were younger than patients treated with DAA without
PEG-IFN (59+/-12y) (P=.001). 47% of patients treated with PEG-IFN+DAA were in the
F4 stage vs 67% of patients treated with DAA without PEG-IFN (P=.001). Screening
was inadequate in 20% of both patient groups (P=.664). The early occurrence rate
of HCC was 1.7% and 1.1% in patients treated with DAA with and without PEG-IFN,
respectively (P=.540). The early recurrence rate was 0% in patients treated with
PEG-IFN+DAA and 15.0% in patients treated with DAA without PEG-IFN (P=.857).
There is no difference in early occurrence of new HCC between patients treated
with DAA with and without PEG-IFN. We did observe a high early recurrence rate of
HCC in patients treated with DAA without PEG-IFN. However, these patients were at
baseline more at risk for HCC. Finally, in 20%, screening for HCC was inadequate.
PMID- 28504856
TI - Cell-free DNA copy number variations in plasma from colorectal cancer patients.
AB - To evaluate the clinical utility of cell-free DNA (cfDNA), we performed whole
genome sequencing to systematically examine plasma cfDNA copy number variations
(CNVs) in a cohort of patients with colorectal cancer (CRC, n = 80), polyps (n =
20), and healthy controls (n = 35). We initially compared cfDNA yield in 20
paired serum-plasma samples and observed significantly higher cfDNA concentration
in serum (median = 81.20 ng, range 7.18-500 ng.mL-1 ) than in plasma (median =
5.09 ng, range 3.76-62.8 ng.mL-1 ) (P < 0.0001). However, tumor-derived cfDNA
content was significantly lower in serum than in matched plasma samples tested.
With ~10 million reads per sample, the sequencing-based copy number analysis
showed common CNVs in multiple chromosomal regions, including amplifications on
1q, 8q, and 5q and deletions on 1p, 4q, 8p, 17p, 18q, and 22q. Copy number
changes were also evident in genes critical to the cell cycle, DNA repair, and
WNT signaling pathways. To evaluate whether cumulative copy number changes were
associated with tumor stages, we calculated plasma genomic abnormality in colon
cancer (PGA-C) score by summing the most significant CNVs. The PGA-C score showed
predictive performance with an area under the curve from 0.54 to 0.84 for CRC
stages I-IV. Locus-specific copy number analysis identified nine genomic regions
where CNVs were significantly associated with survival in stage III-IV CRC
patients. A multivariate model using six of nine genomic regions demonstrated a
significant association of high-risk score with shorter survival (HR = 5.33, 95%
CI = 6.76-94.44, P < 0.0001). Our study demonstrates the importance of using
plasma (rather than serum) to test tumor-related genomic variations. Plasma cfDNA
based tests can capture tumor-specific genetic changes and may provide a
measurable classifier for assessing clinical outcomes in advanced CRC patients.
PMID- 28504858
TI - AJIPHASE(r): A Highly Efficient Synthetic Method for One-Pot Peptide Elongation
in the Solution Phase by an Fmoc Strategy.
AB - We previously reported an efficient peptide synthesis method, AJIPHASE(r), that
comprises repeated reactions and isolations by precipitation. This method
utilizes an anchor molecule with long-chain alkyl groups as a protecting group
for the C-terminus. To further improve this method, we developed a one-pot
synthesis of a peptide sequence wherein the synthetic intermediates were isolated
by solvent extraction instead of precipitation. A branched-chain anchor molecule
was used in the new process, significantly enhancing the solubility of long
peptides and the operational efficiency compared with the previous method, which
employed precipitation for isolation and a straight-chain aliphatic group.
Another prerequisite for this solvent-extraction-based strategy was the use of
thiomalic acid and DBU for Fmoc deprotection, which facilitates the removal of
byproducts, such as the fulvene adduct.
PMID- 28504857
TI - Hysteroscopic resection of a uterine caesarean scar defect (niche) in women with
postmenstrual spotting: a randomised controlled trial.
AB - OBJECTIVE: To compare the effectiveness of a hysteroscopic niche resection versus
no treatment in women with postmenstrual spotting and a uterine caesarean scar
defect. DESIGN: Multicentre randomised controlled trial. SETTING: Eleven
hospitals collaborating in a consortium for women's health research in the
Netherlands. POPULATION: Women reporting postmenstrual spotting after a caesarean
section who had a niche with a residual myometrium of >=3 mm, measured during
sonohysterography. METHODS: Women were randomly allocated to hysteroscopic niche
resection or expectant management for 6 months. MAIN OUTCOME MEASURES: The
primary outcome was the number of days of postmenstrual spotting 6 months after
randomisation. Secondary outcomes were spotting at the end of menstruation,
intermenstrual spotting, dysuria, sonographic niche measurements, surgical
parameters, quality of life, women's satisfaction, sexual function, and
additional therapy. Outcomes were measured at 3 months and, except for niche
measurements, also at 6 months after randomisation. RESULTS: We randomised 52
women to hysteroscopic niche resection and 51 women to expectant management. The
median number of days of postmenstrual spotting at baseline was 8 days in both
groups. At 6 months after randomisation, the median number of days of
postmenstrual spotting was 4 days (interquartile range, IQR 2-7 days) in the
intervention group and 7 days (IQR 3-10 days) in the control group (P = 0.04); on
a scale of 0-10, discomfort as a result of spotting had a median score of 2 (IQR
0-7) in the intervention group, compared with 7 (IQR 0-8) in the control group (P
= 0.02). CONCLUSIONS: In women with a niche with a residual myometrium of >=3 mm,
hysteroscopic niche resection reduced postmenstrual spotting and spotting-related
discomfort. TWEETABLE ABSTRACT: A hysteroscopic niche resection is an effective
treatment to reduce niche-related spotting.
PMID- 28504859
TI - Anxiety: There is an app for that. A systematic review of anxiety apps.
AB - BACKGROUND: Smartphones and mobile devices have become ubiquitous, and with the
rapid advance of technology, the number of health applications (apps) that are
available for consumers on these devices is constantly growing. In particular,
there has been a recent proliferation of anxiety apps. However, there has been no
review of the quality or content of these anxiety apps and little is known about
their purpose, the features they contain, and their empirical support. The goal
of this systematic review was to assess the commercially available anxiety apps.
METHODS: A list of anxiety apps was collected in January 2017, using the Power
Search function of iTunes and Google Play. Of 5,078 identified apps, 52 met our
inclusion criteria (i.e., being defined as an anxiety/worry relief app, and
offering psychological techniques aimed primarily at reducing anxiety) and were
further reviewed. RESULTS: The majority (67.3%) of the currently available
anxiety apps were found to lack the involvement of health care professionals in
their development, and very few (3.8%) of them have been rigorously tested.
CONCLUSIONS: At the moment, although anxiety apps have the potential to enhance
access to mental health care, there is a marked discrepancy between the wealth of
commercially available apps, and the paucity of data regarding their efficacy and
effectiveness. Although the great promise of apps is their ability to increasing
access to evidence-based mental health, the field is not quite there yet and the
full potential of apps for treating anxiety has yet to be exploited.
PMID- 28504862
TI - Polyadenine-Modulated DNA Conformation Monitored by Surface-Enhanced Raman
Scattering (SERS) on Multibranched Gold Nanoparticles and Its Sensing
Application.
AB - This work proposes a facile way to modulate the conformation of DNA from the "Lie
Down" to the "Stand-Up" conformation on the surface of multibranched gold
nanoparticles (AuNPs). This is realized by regulating the length of polyadenine
(polyA) linked to the DNA sequence and/or the hybridization of this sequence with
the target DNA, and can be monitored by the Raman signal owing to the excellent
performance of multibranched AuNPs (AuNSs) as a surface-enhanced Raman scattering
(SERS) substrate and the distance change between the Raman reporter and the
substrate. The probable mechanism, which depends on the repulsion of polyA from
the sequence and the tip assembly, has also been probed through theoretical
simulation using the finite difference time domain method. By virtue of this
strategy, a conformation-transformation-based DNA@AuNS sensor is constructed for
the identification of a specific oligonucleotide, which has been used for the
detection of DNA sequences associated with Severe Acute Respiratory Syndrome
(SARS). This strategy leads to a novel sensing platform with good extendibility
for DNA analysis, and provides a powerful protocol for facilitating the cognition
of DNA conformation on metal surfaces.
PMID- 28504860
TI - Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells Expanded In Vitro for
Treatment of Aplastic Anemia: A Multicenter Phase II Trial.
AB - We conducted a phase II, noncomparative, multicenter study to assess the efficacy
and safety of allogeneic bone marrow-derived mesenchymal stromal cells (BM-MSCs)
expanded in vitro for patients with aplastic anemia (AA) refractory to
immunosuppressive therapy. Seventy-four patients from seven centers received
allogeneic BM-MSCs at a dose of 1-2 * 106 cells/kg per week for 4 weeks.
Responses were assessed at 0.5, 1, 2, 3, 6, 9, and 12 months after the first
cells infusion. Patients with response at 1 month continued to receive four
infusions. All patients were evaluable. The overall response rate was 28.4% (95%
confidence interval, 19%-40%), with 6.8% complete response and 21.6% partial
response. The median times to response of leukocytic, erythrocytic, and
megakaryocytic linages were 19 (range, 11-29), 17 (range, 12-25), and 31 (range,
26-84) days, respectively. After median follow-up of 17 months, overall survival
was 87.8%. Seven patients developed transitory and mild headache and fever, but
no other adverse events were observed. Antithymocyte globulin used in previous
treatment and no activated infection throughout treatment were predictors for
response. Allogeneic BM-MSCs infusion is a feasible and effective treatment
option for refractory AA. The trial was registered at www.clinicaltrials.gov as
NCT00195624. Stem Cells Translational Medicine 2017;6:1569-1575.
PMID- 28504861
TI - The efficacy of benzodiazepines as acute anxiolytics in children: A meta
analysis.
AB - OBJECTIVE: Current practice guidelines do not recommend benzodiazepines for acute
management of anxiety disorders in pediatric patients. However, in procedural
settings, benzodiazepines are commonly used to relieve acute preprocedural
stress. This meta-analysis examines the efficacy and tolerability of
benzodiazepines as short-term anxiolytics in children. METHOD: PubMed was
searched for randomized controlled trials assessing the efficacy of
benzodiazepines as short-term anxiolytics in pediatric patients. Twenty-one
trials involving 1,416 participants were included. A fixed effects model was used
to examine the standardized mean difference of improvement in anxiety levels
compared to control conditions. In stratified subgroup and meta-regression, the
effect of the specific agent, dose, timing, and setting of benzodiazepine
treatment was examined. RESULTS: A significant benefit was seen for
benzodiazepines compared to control (standardized mean difference = 0.71 [95%
confidence interval, 0.60-0.82], k = 24, z = 12.7, P < .001). There was also
funnel plot asymmetry in this meta-analysis, suggesting some evidence of
publication bias. Moderator analyses found that when benzodiazepines were used in
dental or nonoperating room procedures, they were more effective than when they
were used in operating room procedures (test for subgroup differences Q2 = 6.34,
P = .04). Tolerability analysis revealed there was no significant difference in
the risk of developing irritability or behavioral changes between benzodiazepine
and control groups. CONCLUSIONS: Benzodiazepines are effective and well-tolerated
when used as short-term anxiolytics in procedural settings for pediatric
patients. Further research is needed to determine whether benzodiazepines are
effective in pediatric anxiety disorders.
PMID- 28504863
TI - Diagnostic accuracy of polymerase chain reaction for intrapartum detection of
group B streptococcus colonization.
AB - INTRODUCTION: Many pregnant women are treated with antibiotics during labor to
prevent transmission of group B streptococcus (GBS, Streptococcus agalactiae) to
their baby during passage of the birth canal, and so reduce the risk of serious
infection of the newborn. Methods for intrapartum testing for GBS have been
introduced to select women to whom intrapartum antibiotic prophylaxis should be
offered. For such an intrapartum test to be useful in clinical practice, it has
to be specific as well as sensitive. The aim of the present study is to evaluate
the accuracy of the polymerase chain reaction (PCR) assay compared with an
optimized culture method for GBS. MATERIAL AND METHODS: In the period from 12 May
2015 to 18 December 2015 we collected rectovaginal swabs from 106 women in the
labor ward presenting in labor between gestational week 35+0 and 36+6 or
presenting with prelabor/preterm prelabor rupture of membranes (PROM/PPROM) for >
14 h after gestational week 34+0 . We performed GBS culture (reference standard)
and a molecular GBS test (Xpert GBS, Cepheid Ltd., Sunnyvale, CA, USA). RESULTS:
Based on intrapartum culture, 23.6% (25/106) were colonized with GBS. Intrapartum
PCR showed a colonization rate of 25.7% (27/105). The sensitivity of the test was
100% (86.28-100%). The specificity of the test was 97.5% (91.26-99.70%). The
positive predictive value was 92.6%. In one case, we had no result with PCR
testing, giving an invalid test rate of < 1%. CONCLUSION: The PCR test has
sufficient accuracy to direct intrapartum antibiotic prophylaxis for GBS
transmission during delivery.
PMID- 28504864
TI - Nitrated Fatty Acids Modulate the Physical Properties of Model Membranes and the
Structure of Transmembrane Proteins.
AB - Nitrated fatty acids (NO2 -FAs) act as anti-inflammatory signal mediators, albeit
the molecular mechanisms behind NO2 -FAs' influence on diverse metabolic and
signaling pathways in inflamed tissues are essentially elusive. Here, we combine
fluorescence measurements with surface-specific sum frequency generation
vibrational spectroscopy and coarse-grained computer simulations to demonstrate
that NO2 -FAs alter lipid organization by accumulation at the membrane-water
interface. As the function of membrane proteins strongly depends on both, protein
structure as well as membrane properties, we consecutively follow the structural
dynamics of an integral membrane protein in presence of NO2 -FAs. Based on our
results, we suggest a molecular mechanism of the NO2 -FA in vivo activity: Driven
by the NO2 -FA-induced lipid layer reorganization, the structure and function of
membrane-associated (signaling) proteins is indirectly affected.
PMID- 28504865
TI - Real-time crystallographic studies of the adenine riboswitch using an X-ray free
electron laser.
AB - Structures of the four reaction states of the adenine riboswitch aptamer domain,
including a transient intermediate state were solved by serial femtosecond
crystallography. The structures not only demonstrate the use of X-ray free
electron lasers for RNA crystallography but have also proven that transient
states can be determined in real time by mix-and-inject crystallography. These
results illustrate the structural basis for the ligand-induced conformational
changes associated with the molecular 'switch'.
PMID- 28504866
TI - A short report on current fertility preservation strategies for boys.
AB - BACKGROUND: Advances in cancer treatment have led to improved long-term survival
after childhood cancer, but often at a price of impaired future fertility.
Fertility preservation (FP) in male children and early adolescents poses unique
challenges as efficacy is unproven. OBJECTIVES: To describe characteristics of
testicular tissue cryopreservation (TTCP) specimens taken from paediatric and
adolescent patients, stratified by age, and prior chemotherapy, if any, and to
demonstrate evidence for germ cells. MATERIALS AND METHODS: Retrospective review
of gonadal biopsies and clinical records of patients consented into the Royal
Children's Hospital FP programme between 1987 and 2015. Tissue was sliced into
blocks, with one section sent for histopathology prior to cryopreservation. In
boys >=12 years where spermatogenesis could be expected, a portion of tissue was
disaggregated completely to look for mature sperm and if found, additional tissue
was dissected and the resulting suspension frozen. RESULTS: Testicular tissue
cryopreservation specimens in 44 males (0.3-16.8 years) provided an average of
7.8 slices per patient. All the specimens were taken at the same time as another
necessary surgical procedure, under one general anaesthesic. There was only one
complication of scrotal wound dehiscence. Seven of the forty-four (15.9%)
patients had chemotherapy prior to testicular biopsy, while the rest were
chemotherapy naive. Five of these were prepubertal, and two were pubertal
patients. Eleven subjects had tissue dissected with mature sperm found in eight.
Of these eight patients where sperm were found, all were pubertal with testicular
size of more than 10 mL and showing histological evidence of spermatogenesis. No
histologic specimen demonstrated any malignant cells. CONCLUSIONS: Testicular
tissue cryopreservation can be performed in young patients without delay,
preferably prior to cancer treatment. As testicular tissue contains germ cells
from which haploid spermatozoa are ultimately derived, future technologies may
allow their utilization for fertility in humans. This may be the only hope for
biological offspring in some patients undergoing fertility compromising
treatment. Retrieval of mature sperm from some pubertal patients, however, offers
realistic hope to these patients of future fertility.
PMID- 28504867
TI - The PTPN13 Y2081D (T>G) (rs989902) polymorphism is associated with an increased
risk of sporadic colorectal cancer.
AB - AIM: Colorectal cancer (CRC) is one of the most common cancers worldwide and,
although the majority of cases are sporadic, its development and progression
depends on a range of factors: environmental, genetic and epigenetic. A variety
of genetic pathways have been described as being crucial in CRC, including
protein tyrosine phosphatases (PTPs). PTPN13 (also called FAP-1) is a non
receptor PTP and interacts with a number of important components of growth and
apoptosis pathways. It is also involved in the inhibition of Fas-induced
apoptosis. METHOD: The single nucleotide polymorphism genotype at Y2081D (T>G)
(rs989902) of PTPN13 exon 39 was determined in DNA extracted from blood samples
from 174 sporadic CRC patients and 176 healthy individuals. Also, a meta-analysis
was performed based on three articles accessed via the PubMed and ResearchGate
databases. RESULTS: The risk of CRC was 2.087 times greater for patients with the
GG genotype than for those with the TT genotype (P = 0.0475). In the meta
analysis, a significantly increased risk of cancer associated with the G allele
was observed in the squamous cell carcinoma of the head and neck subgroup (TT vs
GG+GT, OR 1.23, 95% CI [1.02, 1.47], P = 0.0258), and a significantly decreased
risk in the breast cancer subgroup (TT vs GG+GT, OR 0.63, 95% CI [0.41, 0.96], P
= 0.0334) and in the CRC subgroup (GT+TT vs GG, OR 0.51, 95% CI [0.41, 0.95], P =
0.0333). CONCLUSION: PTPN13 rs989902 is significantly associated with the risk of
CRC in the Polish population. Given that this report provides the first evidence
of an association of PTPN13 rs989902 with the risk of CRC in a Caucasian
population, further large scale studies are necessary to confirm this finding.
PMID- 28504868
TI - Recognizing Latinos' range of skin pigment and phototypes to enhance skin cancer
prevention.
AB - Latinos in the United States may have the mistaken assumption that their natural
pigmentation protects them from developing skin cancer that, effectively, serves
as a barrier to Latinos receiving education in primary and secondary prevention
of skin cancer. Latino adults of Mexican or Puerto Rican heritage attending
community health fairs in the greater Chicago area responded to a culturally
informed and sensitive measure for sunburn and tan, which was previously adapted
to capture skin irritation with tenderness from the sun occurring in darker skin
types (n = 350). By self-reported responses and spectrophotometry assessment of
constitutive pigmentation, adapted Fitzpatrick skin types (FST) ranged from skin
type I-IV in the Mexican American participants and from II to V in the Puerto
Rican participants. The objectively measured proportion of adapted FST II skin
type was greater than commonly perceived and demonstrated that many Latinos do
indeed have sun-sensitive skin.
PMID- 28504869
TI - Kidney outcomes in patients with liver cirrhosis and chronic kidney disease
receiving an orthotopic liver transplant alone.
AB - Kidney transplant in patients with liver cirrhosis and nondialysis chronic kidney
disease (CKD) is controversial. We report 14 liver cirrhotic patients who had
persistently low MDRD-6 estimated glomerular filtration rate (e-GFR) <40
mL/min/1.73 m2 for >=3 months and underwent either liver transplant alone (LTA;
n=9) or simultaneous liver-kidney transplant (SLKT; n=5). Pretransplant, patients
with LTA compared with SLKT had lower serum creatinine (2.5+/-0.73 vs 4.6+/-0.52
mg/dL, P=.001), higher MDRD-6 e-GFR (21.0+/-7.2 vs 10.3+/-2.0 mL/min/1.73 m2 ,
P=.002), higher 24-hour urine creatinine clearance (34.2+/-8.8 vs 18.0+/-2.2
mL/min, P=.002), lower proteinuria (133.2+/-117.7 vs 663+/-268.2 mg/24 h,
P=.0002), and relatively normal kidney biopsy and ultrasound findings. Post-LTA,
the e-GFR (mL/min/1.73 m2 ) increased in all nine patients, with mean e-GFR at 1
month (49.8+/-8.4), 3 months (49.6+/-8.7), 6 months (49.8+/-8.1), 12 months
(47.6+/-9.2), 24 months (47.9+/-9.1), and 36 months (45.1+/-7.3) significantly
higher compared to pre-LTA e-GFR (P<=.005 at all time points). One patient
developed end-stage renal disease 9 years post-LTA and another patient expired 7
years post-LTA. The low e-GFR alone in the absence of other markers or risk
factors of CKD should not be an absolute criterion for SLKT in patients with
liver cirrhosis.
PMID- 28504870
TI - A critical evaluation of the current "p-value controversy".
AB - This article has been triggered by the initiative launched in March 2016 by the
Board of Directors of the American Statistical Association (ASA) to counteract
the current p-value focus of statistical research practices that allegedly "have
contributed to a reproducibility crisis in science." It is pointed out that in
the very wide field of statistics applied to medicine, many of the problems
raised in the ASA statement are not as severe as in the areas the authors may
have primarily in mind, although several of them are well-known experts in
biostatistics and epidemiology. This is mainly due to the fact that a large
proportion of medical research falls under the realm of a well developed body of
regulatory rules banning the most frequently occurring misuses of p-values.
Furthermore, it is argued that reducing the statistical hypotheses tests nowadays
available to the class of procedures based on p-values calculated under a
traditional one-point null hypothesis amounts to ignoring important developments
having taken place and going on within the statistical sciences. Although
hypotheses testing is still an indispensable part of the statistical methodology
required in medical and other areas of empirical research, there is a large
repertoire of methods based on different paradigms of inference that provide
ample options for supplementing and enhancing the methods of data analysis blamed
in the ASA statement for causing a crisis.
PMID- 28504872
TI - Comparing student and staff perceptions of the "Educational Climate" in Spanish
Dental Schools using the Dundee Ready Education Environment Measure.
AB - OBJECTIVE: To compare the perceptions of students and teachers of the
"Educational Climate" (EC) in Spanish public dental schools. METHODS: A group of
1064 students and 354 teachers from six Spanish public dental schools responded
to the DREEM questionnaire. This has 50 items grouped into five subscales:
perception of learning (Learning); perception of teachers (Teachers); academic
self-perceptions (Academic); perception of the atmosphere in the faculty
(Atmosphere); and social self-perceptions (Social). The DREEM scale provides
results for each item, each subscale and the overall EC. RESULTS: The EC scores
were 123.2 (61.6%) for the students and 134.1 (67.0%) for the teachers (P<.001).
The scores of the students and teachers for the subscales were, respectively:
27.9 (58.1%) and 30.2 (63.0 %) for Learning (P<.001); 26.8 (60.9%) and 32.6
(74.1%) for Teachers (P<.001); 20.7 (64.7%) and 20.5 (64.0%) for Academic
(P=.333); 29.9 (62.3%) and 33.7 (70.3%) for Atmosphere (P<.001); and 17.9 (64.0%)
and 16.9 (60.5%) for Social (P<.001). The students identified six problematic
items (12.0 %) compared to only two (4.0 %) highlighted by the teachers.
CONCLUSION: The students and teachers considered the EC to be "more positive than
negative" in Spanish public dental schools; and the different subscales to be
"positive and acceptable." The teachers did, however, evaluate the EC, and
specifically the learning-teaching process, more positively than their students,
identifying fewer problematic educational aspects. Both groups agreed on the need
to: improve support systems for students who suffer from stress and reduce
teaching based on "factual learning."
PMID- 28504871
TI - Pollination and breeding system of the enigmatic South African parasitic plant
Mystropetalon thomii (Mystropetalaceae): rodents welcome, but not needed.
AB - Unrelated plants adapted to particular pollinator types tend to exhibit
convergent evolution in floral traits. However, inferences about likely
pollinators from 'pollination syndromes' can be problematic due to trait overlap
among some syndromes and unusual floral architecture in some lineages. An example
is the rare South African parasitic plant Mystropetalon thomii
(Mystropetalaceae), which has highly unusual brush-like inflorescences that
exhibit features of both bird and rodent pollination syndromes. We used camera
traps to record flower visitors, quantified floral spectral reflectance and
nectar and scent production, experimentally determined self-compatibility and
breeding system, and studied pollen dispersal using fluorescent dyes. The dark
red inflorescences are usually monoecious, with female flowers maturing before
male flowers, but some inflorescences are purely female (gynoecious).
Inflorescences were visited intensively by several rodent species that carried
large pollen loads, while visits by birds were extremely rare. Rodents prefer
male- over female-phase inflorescences, likely because of the male flowers'
higher nectar and scent production. The floral scent contains several compounds
known to attract rodents. Despite the obvious pollen transfer by rodents, we
found that flowers on both monoecious and gynoecious inflorescences readily set
seed in the absence of rodents and even when all flower visitors are excluded.
Our findings suggest that seed production occurs at least partially through
apomixis and that M. thomii is not ecologically dependent on its rodent
pollinators. Our study adds another species and family to the growing list of
rodent-pollinated plants, thus contributing to our understanding of the floral
traits associated with pollination by non-flying mammals.
PMID- 28504873
TI - Controlling the Regioselectivity of Baeyer-Villiger Monooxygenases by Mutation of
Active-Site Residues.
AB - Baeyer-Villiger monooxygenase (BVMO)-mediated regiodivergent conversions of
asymmetric ketones can lead to the formation of "normal" or "abnormal" lactones.
In a previous study, we were able to change the regioselectivity of a BVMO by
mutation of the active-site residues to smaller amino acids, which thus created
more space. In this study, we demonstrate that this method can also be used for
other BVMO/substrate combinations. We investigated the regioselectivity of 2-oxo
Delta3 -4,5,5-trimethylcyclopentenylacetyl-CoA monooxygenase from Pseudomonas
putida (OTEMO) for cis-bicyclo[3.2.0]hept-2-en-6-one (1) and trans-dihydrocarvone
(2), and we were able to switch the regioselectivity of this enzyme for one of
the substrate enantiomers. The OTEMO wild-type enzyme converted (-)-1 into an
equal (50:50) mixture of the normal and abnormal products. The F255A/F443V
variant produced 90 % of the normal product, whereas the W501V variant formed up
to 98 % of the abnormal product. OTEMO F255A exclusively produced the normal
lactone from (+)-2, whereas the wild-type enzyme was selective for the production
of the abnormal product. The positions of these amino acids were equivalent to
those mutated in the cyclohexanone monooxygenases from Arthrobacter sp. and
Acinetobacter sp. (CHMOArthro and CHMOAcineto ) to switch their regioselectivity
towards (+)-2, which suggests that there are hot spots in the active site of
BVMOs that can be targeted with the aim to change the regioselectivity.
PMID- 28504875
TI - Selection of Natural Peptide Ligands for Copper-Catalyzed Azide-Alkyne
Cycloaddition Catalysis.
AB - The copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is a powerful
tool for making connections in both organic reactions and biological systems.
However, the use of this ligation process in living cells is limited by the
toxicity associated with unbound copper ions. As an initial attempt to create
peptide-based accelerating ligands capable of cellular expression, we performed
synthesis and selection for such species on solid-phase synthesis beads bearing
both candidate ligand and alkyne substrate. A simple histidine-containing motif
(HXXH) was identified, and found after solution-phase optimization to produce
single-turnover systems showing moderate rate acceleration over the ligand-free
reaction. CuAAC reaction rates and yields for different alkynes were found to
respond to the peptide ligands, demonstrating a substrate scope beyond what was
used for the selection steps, but also illustrating the potential difficulty in
evolving a general CuAAC catalyst.
PMID- 28504876
TI - Whispering Gallery Mode Laser from Carbon Dot-NaCl Hybrid Crystals.
AB - Carbon dot (CD)-NaCl hybrid crystals are obtained by incorporating the CDs into
NaCl matrix through a simple process. The embedded CDs have added the
luminescence centers into NaCl, and as a result, the hybrid crystals present the
fluorescence centered at 510 nm under the illumination of 365 nm light.
Meanwhile, the phosphorescence with an average lifetime of 314 ms is achieved
after the 365 nm light was turned off. Furthermore, optical gain and lasing
phenomenon has been observed from hybrid crystals. When the pump power is low, a
weak spontaneous emission can be observed from the hybrid crystal, whereas the
lasing action was observed under high pump power. The lasing threshold is found
to be 0.08 mW and corresponding Q factor is calculated to be 447. The tiny cubic
crystal in hybrid crystals offers the whispering gallery mode (WGM) resonant
cavity for lasing emission. That has provided a new approach for realizing lasing
materials.
PMID- 28504877
TI - Illuminating Superoxide Anion and pH Enhancements in Apoptosis of Breast Cancer
Cells Induced by Mitochondrial Hyperfusion Using a New Two-Photon Fluorescence
Probe.
AB - Mitochondrial morphology regulated by fusion and fission processes determines
mitochondrial function and cell fate. Some studies showed hyperfused mitochondria
could induce apoptosis in cancer cells, but the relevant molecular mechanisms
remain elusive. Superoxide (O2*-) and pH play vital roles in mitochondrial
dysfunction and apoptosis. Therefore, it is worthwhile to explore if there is an
intimate relationship between mitochondrial hyperfusion and simultaneous changes
in O2*- and pH levels, which will be helpful to uncover relevant detailed
mechanism. For this purpose, we have developed a new reversible two-photon
fluorescent probe (CFT) to simultaneously monitor O2*- and pH in 4T1 cells and
mice using dual-color imaging. With the assistance of probe, we found that
inhibition of Dynamin-related protein 1 (Drp1) could transduce a signal through
mitochondrial complexes I and II to enhance the O2*- and pH levels and eventually
induced mitohyperfusion and apoptosis in breast cancer cells. Together, these
data indicate that CFT provides a robust tool for unveiling the roles of O2*- and
pH in signals associated with mitochondrial dysfunction in cells and in vivo.
PMID- 28504874
TI - Cranioplasty with Adipose-Derived Stem Cells, Beta-Tricalcium Phosphate Granules
and Supporting Mesh: Six-Year Clinical Follow-Up Results.
AB - Several alternative techniques exist to reconstruct skull defects. The
complication rate of the cranioplasty procedure is high and the search for
optimal materials and techniques continues. To report long-term results of
patients who have received a cranioplasty using autologous adipose-derived stem
cells (ASCs) seeded on beta-tricalcium phosphate (betaTCP) granules. Between
10/2008 and 3/2010, five cranioplasties were performed (four females, one male;
average age 62.0 years) using ASCs, betaTCP granules and titanium or resorbable
meshes. The average defect size was 8.1 * 6.7 cm2 . Patients were followed both
clinically and radiologically. The initial results were promising, with no
serious complications. Nevertheless, in the long-term follow-up, three of the
five patients were re-operated due to graft related problems. Two patients showed
marked resorption of the graft, which led to revision surgery. One patient
developed a late infection (7.3 years post-operative) that required revision
surgery and removal of the graft. One patient had a successfully ossified graft,
but was re-operated due to recurrence of the meningioma 2.2 years post
operatively. One patient had an uneventful clinical follow-up, and the cosmetic
result is satisfactory, even though skull x-rays show hypodensity in the borders
of the graft. Albeit no serious adverse events occurred, the 6-year follow-up
results of the five cases are unsatisfactory. The clinical results are not
superior to results achieved by conventional cranial repair methods. The use of
stem cells in combination with betaTCP granules and supporting meshes in cranial
defect reconstruction need to be studied further before continuing with clinical
trials. Stem Cells Translational Medicine 2017;6:1576-1582.
PMID- 28504878
TI - Raspberry-like Nanostructured Silicon Composite Anode for High-Performance
Lithium-Ion Batteries.
AB - Adjusting the particle size and nanostructure or applying carbon materials as the
coating layers is a promising method to hold the volume expansion of Si for its
practical application in lithium-ion batteries (LIBs). Herein, the mild carbon
coating combined with a molten salt reduction is precisely designed to synthesize
raspberry-like hollow silicon spheres coated with carbon shells (HSi@C) as the
anode materials for LIBs. The HSi@C exhibits a remarkable electrochemical
performance; a high reversible specific capacity of 886.2 mAh g-1 at a current
density of 0.5 A g-1 after 200 cycles is achieved. Moreover, even after 500
cycles at a current density of 2.0 A g-1, a stable capacity of 516.7 mAh g-1
still can be obtained.
PMID- 28504880
TI - Navigating Past a Fork in the Road: Carbocation-pi Interactions Can Manipulate
Dynamic Behavior of Reactions Facing Post-Transition-State Bifurcations.
AB - Dynamics calculations are described for carbocation rearrangements involving
product-forming pathways with post-transition-state bifurcations. We show that
noncovalent interactions with associated benzene rings (a simple model of
aromatic amino acid side chains) can switch inherent dynamical tendencies for
competing modes of disrotation, establishing that meaningful changes in
dynamically controlled product selectivity can be achieved with few weak
noncovalent interactions.
PMID- 28504881
TI - Compartmentalization Technologies via Self-Assembly and Cross-Linking of
Amphiphilic Random Block Copolymers in Water.
AB - Orthogonal self-assembly and intramolecular cross-linking of amphiphilic random
block copolymers in water afforded an approach to tailor-make well-defined
compartments and domains in single polymer chains and nanoaggregates. For a
double compartment single-chain polymer, an amphiphilic random block copolymer
bearing hydrophilic poly(ethylene glycol) (PEG) and hydrophobic dodecyl, benzyl,
and olefin pendants was synthesized by living radical polymerization (LRP) and
postfunctionalization; the dodecyl and benzyl units were incorporated into the
different block segments, whereas PEG pendants were statistically attached along
a chain. The copolymer self-folded via the orthogonal self-assembly of
hydrophobic dodecyl and benzyl pendants in water, followed by intramolecular
cross-linking, to form a single-chain polymer carrying double yet distinct
hydrophobic nanocompartments. A single-chain cross-linked polymer with a chlorine
terminal served as a globular macroinitiator for LRP to provide an amphiphilic
tadpole macromolecule comprising a hydrophilic nanoparticle and a hydrophobic
polymer tail; the tadpole thus self-assembled into multicompartment aggregates in
water.
PMID- 28504879
TI - Antitubercular Activity of Mycelium-Associated Ganoderma Lanostanoids.
AB - In a continuation of our research into antitubercular lanostane triterpenoids
from submerged cultures of Ganoderma species, three strains, Ganoderma orbiforme
BCC 22325, Ganoderma sp. BCC 60695, and Ganoderma australe BCC 22314, have been
investigated. Fourteen new lanostane triterpenoids, together with 35 known
compounds, were isolated. Antitubercular activities of these mycelium-associated
Ganoderma lanostanoids against Mycobacterium tuberculosis H37Ra were evaluated.
Taken together with the assay data of previously isolated compounds, structure
activity relationships of the antitubercular activity are proposed. Most
importantly, 3beta- and 15alpha-acetoxy groups were shown to be critical for
antimycobacterial activity. The most potent compound was (24E)-3beta,15alpha
diacetoxylanosta-7,9(11),24-trien-26-oic acid (35).
PMID- 28504882
TI - Visible-Light-Induced Tandem Radical Addition-Cyclization of Alkenyl Aldehydes
Leading to Indanones and Related Compounds.
AB - Herein we describe a novel, visible light-induced tandem radical addition
cyclization of alkenyl aldehydes with alpha-bromocarbonyl compounds. A set of
cyclic ketones, including indanones, cyclopentenones, 3,4-dihydronaphthalen-1(2H)
ones, and chroman-4-ones, are synthesized at room temperature with high
efficiency and good functional group compatibility. It represents the first
report on the catalytic 1,2-acylalkylation of unactivated alkenes.
PMID- 28504883
TI - Synergetic Effect of Monomer Functional Group Coordination in Catalytic Insertion
Polymerization.
AB - PhS- and PhNH-functionalized dienes are copolymerized efficiently with butadiene
to stereoregular copolymers by [(mesitylene)Ni(allyl)][BArF4] (Ni-1). Overall
polymerization rates and comonomer incorporations depend strongly on the linker
length between the diene moiety and functional group, in, e.g., PhS-(CH2)xC(?CH2)
CH?CH2 (PhS-x-BD, x = 3-7), in particular for certain linker lengths high
comonomer reactivity ratios stand out. This effect is related to a favorable
binding of the comonomer to the active site comprising coordination of its
functional group, which significantly enhances comonomer incorporation in the
growing polymer chain.
PMID- 28504884
TI - d-alpha-Tocopheryl Succinate/Phosphatidyl Ethanolamine Conjugated Amphiphilic
Polymer-Based Nanomicellar System for the Efficient Delivery of Curcumin and To
Overcome Multiple Drug Resistance in Cancer.
AB - Nanomedicines have emerged as a promising treatment strategy for cancer. Multiple
drug resistance due to overexpression of various drug efflux transporters and
upregulation of apoptotic inhibitory pathways in cancer cells are major barriers
that limit the success of chemotherapy. Here, we developed a d-alpha-tocopherol
(alpha-TOS)/lipid-based copolymeric nanomicellar system (VPM) by conjugating
phosphatidyl ethanolamine (PE) and alpha-TOS with poly(ethylene glycol) (PEG) via
an amino acid linkage. The synthesized polymers were characterized by Fourier
transform IR, gas-phase chromatography, and 1H and 13C NMR spectroscopy. VPM
exhibited mean hydrodynamic diameter of 141.0 +/- 0.94 nm with low critical
micelles concentrations (CMC) of 15 MUM compared to plain PEG-PE micelles (PPM)
with size of 23.9 +/- 0.34 nm and CMC 20 MUM. The bigger hydrophobic compartment
in VPM resulted in improved loading of a potent chemotherapeutic drug, curcumin
(Cur), and increased encapsulation efficiency (EE) (% drug loading 98.3 +/- 1.92,
and 85.3 +/- 3.29; EE 14.8 +/- 0.16 and 12.8 +/- 0.09 for VPM and PPM,
respectively). Curcumin loaded Vitamin E based micelles exhibited higher
cytotoxicity compared to Curcumin loaded PEG-PE micelles in tested cancer cell
lines. C-VPM demonstrated ~3.2 and ~2.7-fold higher ability to reverse multiple
drug resistance compared to PPM and verapamil (concentration used 30 MUM),
respectively. In the in vivo study by using B16F10 implanted C57Bl6/J mice, C-VPM
reduced the tumor volume and weight more efficiently than C-PPM by inducing
apoptosis as analyzed by TUNEL assay on tumor cryosections. The newly developed
polymeric micelles, VPM with improved drug loadability and ability to reverse the
drug resistance could successfully be utilized as a nanocarrier system for
hydrophobic chemotherapeutic agents for the treatment of drug-resistant solid
tumors.
PMID- 28504885
TI - Uranyl Coordination by the 14-Membered Macrocycle
Dibenzotetramethyltetraaza[14]annulene.
AB - Reaction of [UO2(N(SiMe3)2)2(THF)2] with 1 equiv of
dibenzotetramethyltetraaza[14]annulene (tmtaaH2) affords the uranyl complex
[UO2(tmtaaH)(N(SiMe3)2) (THF)] (1) (THF = tetrahydrofuran) as red blocks in 83%
yield. Similarly, thermolysis of a mixture of [UO2(N(SiMe3)2)2(THF)2] and 2 equiv
of tmtaaH2 affords [UO2(tmtaaH)2] (2), which can be isolated as red-orange
crystals in 67% yield after workup. Both 1 and 2 were fully characterized,
including analysis by X-ray crystallography. The tmtaaH ligands in 1 and 2 are
only coordinated to the uranium center via one beta-diketiminate fragment, while
the protonated beta-diketimine portion of the ligand remains uncoordinated.
Reaction of [UO2(N(SiMe3)2)2(THF)2] with 1 equiv of Li2(tmtaa) in C6H6 results in
the formation of [Li(THF)]2[UO2(N(SiMe3)2)2(tmtaa)] (3), which can be isolated in
55% yield as a red-brown crystalline solid. The tmtaa ligand in complex 3
supports a dative interaction between an oxo ligand in the uranyl fragment and a
lithium cation, suggesting that tmtaa could be a useful ligand for developing the
oxo ligand functionalization chemistry of the uranyl ion.
PMID- 28504886
TI - Nanoparticle-Delivered 2-PAM for Rat Brain Protection against Paraoxon Central
Toxicity.
AB - Solid lipid nanoparticles (SLNs) are among the most promising nanocarriers to
target the blood-brain barrier (BBB) for drug delivery to the central nervous
system (CNS). Encapsulation of the acetylcholinesterase reactivator, pralidoxime
chloride (2-PAM), in SLNs appears to be a suitable strategy for protection
against poisoning by organophosphorus agents (OPs) and postexposure treatment. 2
PAM-loaded SLNs were developed for brain targeting and delivery via intravenous
(iv) administration. 2-PAM-SLNs displayed a high 2-PAM encapsulation efficiency
(~90%) and loading capacity (maximum 30.8 +/- 1%). Drug-loaded particles had a
mean hydrodynamic diameter close to 100 nm and high negative zeta potential (-54
to -15 mV). These properties contribute to improve long-term stability of 2-PAM
SLNs when stored both at room temperature (22 degrees C) and at 4 degrees C, as
well as to longer circulation time in the bloodstream compared to free 2-PAM.
Paraoxon-poisoned rats (2 * LD50) were treated with 2-PAM-loaded SLNs at a dose
of 2-PAM of 5 mg/kg. 2-PAM-SLNs reactivated 15% of brain AChE activity. Our
results confirm the potential use of SLNs loaded with positively charged oximes
as a medical countermeasure both for protection against OPs poisoning and for
postexposure treatment.
PMID- 28504887
TI - CO2-Controlled One-Pot Synthesis of AB, ABA Block, and Statistical Terpolymers
from beta-Butyrolactone, Epoxides, and CO2.
AB - Terpolymerizations of (rac)-beta-butyrolactone (BBL), cyclohexene oxide (CHO),
and carbon dioxide were realized in one-pot reactions utilizing a Lewis acid
BDICF3-Zn-N(SiMe3)2 (1) catalyst. The type of polymerization can be regulated and
switched between ring-opening polymerization (ROP) of BBL and CHO/CO2
copolymerization by the presence of CO2 in the reaction mixture. Applying 3 bar
CO2 to the three-component system leads to similar reaction rates for
copolymerization and ROP and therefore to a terpolymer with a statistical
composition, whereas 40 bar CO2 affords exclusive copolymerization of CHO/CO2.
Two-dimensional NMR spectroscopy and polarimetry provided a deeper understanding
of the underlying mechanism. Furthermore, copolymerization of cyclopentene oxide
(CPO) and CO2 was performed, resulting in the highest reported TOF of 3200 h-1
together with 99% polycarbonate selectivity. Terpolymerizations of CPO/CO2 and
BBL were successfully conducted using the established reaction pathways.
PMID- 28504888
TI - Cytotoxic Bagremycins from Mangrove-Derived Streptomyces sp. Q22.
AB - New bagremycins C-E (3-5) and bagrelactone A (6), together with known bagremycins
A (1) and B (2), 4-hydroxystyrene (7), and 4-hydroxystyrene 4-O-alpha-d
galactopyranoside (8), were isolated from a mangrove-derived actinomycete,
Streptomyces sp. Q22. Structures of these new compounds were elucidated based on
their NMR and HRESIMS spectroscopic data as well as chemical degradation.
Bagremycin C (3) is a unique analogue with an N-acetyl-(S)-cysteine moiety, while
bagrelactone A (6) represents the first example of this type of bagremycin
derived macrolide. Bagremycin C (3) was active against four glioma cell lines,
with IC50 values in the range from 2.2 to 6.4 MUM, induced apoptosis in human
glioma U87MG cells in a dose- and time-dependent manner, and arrested the U87MG
cell cycle at the G0/G1 phase.
PMID- 28504889
TI - Genetic Characterization of vanA-Enterococcus faecium Isolates from Wild Red
Legged Partridges in Portugal.
AB - Vancomycin-resistant enterococci (VRE) have been detected in wild animals
representing a public health concern. The red-legged partridge (Alectoris rufa)
is a common game bird and its meat is consumed in several countries, including
Portugal. Three hundred five fecal samples of red-legged partridge from the north
of Portugal were screened for VRE. Samples were cultured on Slanetz-Bartley agar
supplemented with vancomycin (4 mg/L) and six vanA-Enterococcus faecium were
recovered. Isolates were tested for antibiotic resistance and virulence genes.
Multilocus sequence typing (MLST) was performed to study the genotypic diversity
of vanA-containing E. faecium. The six isolates showed erythromycin resistance
and harbored the erm(B) gene and the four that were tetracycline resistant showed
the tet(M) gene. The C-terminal region of the pbp5 gene of the ampicillin
resistant isolates (minimal inhibitory concentration range of 256 MUg/ml) was
sequenced. Two different pbp5 alleles were detected when considering the changes
of amino acid in 461-629 region. All isolates harbored the esp gene, whereas hyl,
together with the esp gene, was detected in five isolates. MLST analysis grouped
the isolates as ST448 (n = 1), ST139 (n = 1), and ST18 (n = 4). Our findings show
that the red-legged partridges could be a reservoir of antimicrobial resistance
genes and may contribute to the dissemination and transference of the resistance
genes to other animals and humans.
PMID- 28504890
TI - A brief perspective of drug resistance toward EGFR inhibitors: the crystal
structures of EGFRs and their variants.
AB - The EGFR is one of the most popular targets for anticancer therapies and many
drugs, such as erlotinib and gefitinib, have got enormous success in clinical
treatments of cancer in past decade. However, the efficacy of these agents is
often limited because of the quick emergence of drug resistance. Fundamental
structure researches of EGFR in recent years have generally elucidated the
mechanism of drug resistance. In this review, based on systematic resolution of
full structures of EGFR and their variants via single crystal x-ray
crystallography, the working and drug resistance mechanism of EGFR-targeted drugs
are fully illustrated. Moreover, new strategies for avoiding EGFR drug resistance
in cancer treatments are also discussed.
PMID- 28504891
TI - Intelligence and Fitness: The Mediating Role of Educational Level.
AB - The evolutionary status of intelligence is not clear: It is positively related to
various indicators of fitness but negatively to reproductive success as the most
important fitness marker. In the present research, we explored the links between
intelligence and three fitness indicators: number of children (short-term
reproductive success), number of grandchildren (long-term reproductive success),
and age at first birth. Participants were individuals in a postreproductive stage
( N = 191; mean age = 66.5 years). Intelligence had a positive correlation with
short-term reproductive success and age at first birth but a negative correlation
with long-term reproductive success. Participants' education turned out to be a
significant mediator of the link between intelligence and criterion measures. The
results showed that intelligence can elevate short-term reproductive success.
Furthermore, individuals with higher intellectual abilities tended to delay
reproduction, which negatively affected their long-term reproductive success.
Education was revealed as a very important resource which affects the link
between cognitive abilities and fitness, thus proving its evolutionary role in
contemporary populations.
PMID- 28504892
TI - Palliative Care Interventions before Left Ventricular Assist Device Implantation
in Both Bridge to Transplant and Destination Therapy.
AB - BACKGROUND: The optimal level of palliative care (PC) involvement in left
ventricular assist device (LVAD) therapy has yet to be determined. OBJECTIVE:
Describe the feasibility of PC intervention to elucidate patients' goals and
values in LVAD therapy in both destination therapy (DT) and bridge to transplant
(BTT). DESIGN: Single center, prospective, single-arm study. SETTING/SUBJECTS:
All patients who received mandatory PC consultation, using a semistructured
script, before LVAD implantation (PreVAD evaluation). MEASUREMENTS: We evaluated
the feasibility of PreVAD evaluation and family awareness by analyzing responses
and compared it between DT and BTT. We examined the association between
withdrawal of LVAD therapy and family awareness in death cases. RESULTS: Between
January 2014 and September 2016, 112 patients (DT, 75; BTT, 37) underwent PreVAD
evaluation. All patients could express what makes their life meaningful, and 101
(92.0%) could discuss possible complications. Seventy-nine patients (70.5%) could
articulate their unacceptable health state. There was no difference between both
groups. Family awareness increased significantly from 33.0% to 58.0% after PreVAD
evaluation (p < 0.01). Five LVADs were deactivated among the 12 death cases, and
they were all from the family-aware group (71.2% vs. 0%, p = 0.027). CONCLUSIONS:
Integrated PC intervention was feasible for both BTT and DT patients. Such an
intervention may increase family awareness of the patient's unique concerns and
may have an impact on decision making at the end of life.
PMID- 28504893
TI - Dual inhibitors of cholinesterases and monoamine oxidases for Alzheimer's
disease.
AB - Accumulating evidence indicates a solid relationship between several enzymes and
Alzheimer's disease. Cholinesterases and monoamine oxidases are closely
associated with the disease symptomatology and progression and have been tackled
simultaneously using several multifunctional ligands. This design strategy offers
great chances to alter the course of Alzheimer's disease, in addition to
alleviation of the symptoms. More than 15 years of research has led to the
identification of various dual cholinesterase/monoamine oxidase inhibitors, while
some showing positive outcomes in clinical trials, thus giving rise to additional
research efforts in the field. The aim of this review is to provide an update on
the novel dual inhibitors identified recently and to shed light on their
therapeutic potential.
PMID- 28504894
TI - Preventing Burdensome Transitions of Nursing Home Residents with Advanced
Dementia: It's More than Advance Directives.
AB - BACKGROUND: Although a palliative approach to care is recommended for people with
advanced dementia, many nursing home (NH) residents with dementia experience
burdensome interventions such as hospital transfers at the end of life.
OBJECTIVE: The goal of this study was to examine how decisions to transfer NH
residents with advanced dementia are made, from the perspective of NH nurses and
physicians. METHODS: A qualitative, descriptive method was used. Purposive
sampling was used to recruit 20 healthcare providers from 9 NHs. Data collection
included semistructured, open-ended interviews. RESULTS: Decision making
regarding hospital transfer comprised two phases. Phase one, laying the
groundwork, was influenced by the ability of the providers to effectively
establish trust, foreshadow, and illuminate hazards of hospitalization. Phase
two, responding to an acute event, began at the start of an acute event and ended
when a decision was made to either treat the resident in the NH or transfer to
the hospital. Responding to the acute event was influenced by the ability to care
for residents in the NH, the providers' comfort with end-of-life conversations,
and surrogates' preferences. CONCLUSIONS: Advance care planning before an acute
event is only the first step in a process of decision making. Attention to and
support for decision making is needed at the time of each acute event to ensure
that goals of care are maintained.
PMID- 28504896
TI - Pulmonary Arterial Sarcoma Presenting as Acute Pulmonary Embolism.
PMID- 28504895
TI - Progress toward inhibitors of metallo-beta-lactamases.
AB - The global overuse of antibiotics has led to the emergence of drug-resistant
pathogenic bacteria. Bacteria can combat beta-lactams by expressing beta
lactamases. Inhibitors of one class of beta-lactamase, the serine-beta
lactamases, are used clinically to prevent degradation of beta-lactam
antibiotics. However, a second class of beta-lactamase, the metallo-beta
lactamases (MBLs), function by a different mechanism to serine-beta-lactamases
and no inhibitors of MBLs have progressed to be used in the clinic. Bacteria that
express MBLs are an increasingly important threat to human health. This review
outlines various approaches taken to discover MBL inhibitors, with an emphasis on
the different chemical classes of inhibitors. Recent progress, particularly new
screening methods and the rational design of potent MBL inhibitors are discussed.
PMID- 28504899
TI - Metabolic Diversity and Novelties in the Oomycetes.
AB - The eukaryotic microbes called oomycetes include many important saprophytes and
pathogens, with the latter exhibiting necrotrophy, biotrophy, or obligate
biotrophy. Understanding oomycete metabolism is fundamental to understanding
these lifestyles. Genome mining and biochemical studies have shown that
oomycetes, which belong to the kingdom Stramenopila, secrete suites of
carbohydrate- and protein-degrading enzymes adapted to their environmental niches
and produce unusual lipids and energy storage compounds. Despite having limited
secondary metabolism, many oomycetes make chemicals for communicating within
their species or with their hosts. Horizontal and endosymbiotic gene transfer
events have diversified oomycete metabolism, resulting in biochemical pathways
that often depart from standard textbook descriptions by amalgamating enzymes
from multiple sources. Gene fusions and duplications have further shaped the
composition and expression of the enzymes. Current research is helping us learn
how oomycetes interact with host and environment, understand eukaryotic diversity
and evolution, and identify targets for drugs and crop protection chemicals.
PMID- 28504900
TI - Corrigendum: Costs of Selective Attention: When Children Notice What Adults Miss.
PMID- 28504897
TI - Clonal Complexes and Antimicrobial Susceptibility Profiles of Staphylococcus
pseudintermedius Isolates from Dogs in the United States.
AB - Staphylococcus pseudintermedius is the primary cause of canine pyoderma and has
been associated with diseases in other animals, including human beings. A high
prevalence of methicillin and multidrug resistance has been reported in this
bacterium in some geographic regions of the United States. Multilocus sequence
type (MLST) 68 was implicated, initially, as the major clonal genotype based on a
limited number of samples. The objectives of this study were to determine the
population genetics of S. pseudintermedius isolated from a cross-section of the
United States using a seven-locus multilocus sequence typing method, to identify
clonal complexes (CCs), and to correlate sequence types with antimicrobial
susceptibility profiles. A total of 190 S. pseudintermedius with 86 different
MLSTs were detected and the constituents of three major CCs of methicillin
resistant S. pseudintermedius (MRSP), CC68, CC71, and CC84, were identified.
Different patterns of resistance were associated with each CC. CC71 from the
United States had notable differences with CC71 studied on other continents with
chloramphenicol, tetracycline, and trimethoprim/sulfamethoxazole resistance. Some
isolates with resistance to the broadest range of drugs tested, including that to
chloramphenicol, had STs unrelated to the major CCs, suggesting the potential for
the emergence of new clonal populations of MRSP that are resistant to most
therapeutically useful antimicrobials.
PMID- 28504898
TI - Dissociable Contributions of Imagination and Willpower to the Malleability of
Human Patience.
AB - The ability to exercise patience is important for human functioning. Although it
is known that patience can be promoted by using top-down control, or willpower,
to override impatient impulses, patience is also malleable-in particular,
susceptible to framing effects-in ways that are difficult to explain using
willpower alone. So far, the mechanisms underlying framing effects on patience
have been elusive. We investigated the role of imagination in these effects. In a
behavioral experiment (Experiment 1), a classic framing manipulation (sequence
framing) increased self-reported and independently coded imagination during
intertemporal choice. In an investigation of neural responses during decision
making (Experiment 2), sequence framing increased the extent to which patience
was related to activation in brain regions associated with imagination, relative
to activation in regions associated with willpower, and increased functional
connectivity of brain regions associated with imagination, but not willpower,
relative to regions associated with valuation. Our results suggest that sequence
framing can increase the role of imagination in decision making without
increasing the exertion of willpower.
PMID- 28504901
TI - Tale of Two Erythropoiesis-Stimulating Agents: Utilization, Dosing, Litigation,
and Costs of Darbepoetin and Epoetin Among South Carolina Medicaid-Covered
Patients With Cancer and Chemotherapy-Induced Anemia.
AB - PURPOSE: The US Food and Drug Administration (FDA) has approved epoetin and
darbepoetin for chemotherapy-induced anemia (CIA). Approved epoetin and
darbepoetin dosing schedules were three times per week and weekly, respectively,
although off-label, less frequent scheduling was common. In 2004, 2007, and 2008,
a US Food and Drug Administration Advisory Committees warned of risks associated
with erythropoiesis-stimulating agents. During this period, lawsuits alleging
illegal darbepoetin marketing practices have concluded, resulting in $1.1 billion
in fines and settlements and one criminal conviction. No prior study, to our
knowledge, has reported on the use of darbepoetin versus epoetin for CIA.
METHODS: We evaluated the dosing, utilization, and costs of erythropoiesis
stimulating agents among 3,761 South Carolina Medicaid patients with CIA.
RESULTS: Epoetin and darbepoetin utilization rates were 22% and 28% in 2003, 10%
and 33% in 2007, and 3% and 7% in 2010, respectively. Mean per-patient per
administration epoetin and darbepoetin doses were 40,983 IU and 191 ug,
respectively, in 2003 and 47,753 IU and 369 ug, respectively, in 2010. Mean
monthly patient costs for epoetin and darbepoetin were $1,030 and $981,
respectively, in 2003 and $932 and $1,352, respectively, in 2010. Epoetin use
decreased steadily between 2002 and 2010; darbepoetin use increased steadily
between 2003 and 2007 and then decreased steadily thereafter. Per-patient dosing
of darbepoetin, but not epoetin, increased steadily between 2003 and 2010, and
monthly per-patient epoetin costs decreased 3% while the per-patients costs of
darbepoetin increased 30% between 2003 and 2010. CONCLUSION: To our knowledge,
our findings are the first data reporting on epoetin versus darbepoetin use for
CIA and support recently concluded lawsuits involving allegations of illegal
marketing practices of the manufacturer of darbepoetin.
PMID- 28504902
TI - Reply to C.D. Woodrell et al.
PMID- 28504903
TI - Hepatocellular Carcinoma: A Wrinkle in the Emerging Palliative Care/Oncology
Paradigm.
PMID- 28504904
TI - Application of Panel-Based Tests for Inherited Risk of Cancer.
AB - Next-generation or massively parallel sequencing has transformed the landscape of
genetic testing for cancer susceptibility. Panel-based genetic tests evaluate
multiple genes simultaneously and rapidly. Because these tests are frequently
offered in clinical settings, understanding their clinical validity and utility
is critical. When evaluating the inherited risk of breast and ovarian cancers,
panel-based tests provide incremental benefit compared with BRCA1/2 genetic
testing. For inherited risk of other cancers, such as colon cancer and
pheochromocytoma-paraganglioma, the clinical utility and yield of panel-based
testing are higher; in fact, simultaneous evaluation of multiple genes has been
the historical standard for these diseases. Evaluating inherited risk with panel
based testing has recently entered clinical practice for prostate and pancreatic
cancers, with potential therapeutic implications. The resulting variants of
uncertain significance and mutations with unclear actionability pose challenges
to service providers and patients, underscoring the importance of genetic
counseling and data-sharing initiatives. This review explores the evolving
merits, challenges, and nuances of panel-based testing for cancer susceptibility.
PMID- 28504905
TI - Antibiotics for Sepsis: Does Each Hour Really Count, or Is It Incestuous
Amplification?
PMID- 28504906
TI - The Epigenetics of Intrauterine Smoke Exposure: Can Maternal Vitamin C
Supplementation Prevent Neonatal Respiratory Disease?
PMID- 28504907
TI - Early Lung Function Decline in Cystic Fibrosis. Can Registry Data Explain
Divergent Phenotypes?
PMID- 28504908
TI - Mammea longifolia Planch. and Triana Fruit Extract Induces Cell Death in the
Human Colon Cancer Cell Line, SW480, via Mitochondria-Related Apoptosis and
Activation of p53.
AB - The methanol extract of Mammea longifolia Planch. and Triana (M. longifolia)
fruit was studied for anticancer and apoptotic effects in the SW480 colon cancer
cell line. The apoptotic and necrotic effects of M. longifolia were detected by 3
(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) and lactate
dehydrogenase assays, respectively. One hundred MUg/mL of the extract killed
~82.4% of the cells; however, 2% of the death was related to necrosis. The
morphological changes in M. longifolia-stimulated SW480 cells were observed
directly by light microscopy. DNA fragmentation assay was employed to analyze the
apoptosis induction. M. longifolia-treated SW480 cells promoted the expression of
Bax, Bad, cleaved-poly-ADP-ribose polymerase (PARP), and p53 proteins and
decreased the protein expression of pro-caspases Bcl-2 and Bcl-XL. The ratios of
Bax/Bcl-2 and cleaved-PARP/PARP, predictive markers of apoptotic stimuli in
cancer, increased and may play an important role in regulating the progression of
apoptosis. The results suggested that M. longifolia induces cell death via
mitochondrial-related apoptosis in SW480 cells.
PMID- 28504909
TI - Ethanol Extract of Brassica rapa ssp. pekinensis Suppresses Tumor Necrosis Factor
alpha-Induced Inflammatory Response in Human Umbilical Vein Endothelial Cells.
AB - Brassica rapa L. ssp. pekinensis, commonly known as Chinese cabbage, is a
cruciferous vegetable traditionally consumed in east Asia. Although its habitual
consumption could account for the low incidence of chronic vascular inflammation,
the therapeutic and protective potential of phytochemicals derived from Chinese
cabbage has been poorly studied. In this study, we identified the phenolic
compounds, kaempferol and quercetin, from the ethanol extract of Chinese cabbage
(EtCC). We show for the first time that EtCC contains effective phytochemicals
that suppress tumor necrosis factor (TNF)-alpha-induced inflammatory response in
human umbilical vein endothelial cells. The EtCC inhibited TNF-alpha-induced
monocyte adhesion to endothelial cells in a dose-dependent manner. The
antiadhesive activity of EtCC directly correlated with downregulation of
expression and transcription of vascular cell adhesion molecule-1 (VCAM-1). It
was caused by an Nrf-2-dependent mechanism, leading to activation of antioxidant
responsive element-driven promoter. Taken together, these results suggest that
EtCC inhibits the expression of TNF-alpha-induced adhesion molecules through the
indirect transcriptional modulation of VCAM-1 in endothelial cells. In
conclusion, regular consumption of vegetables containing dietary phytochemicals
might be a potential therapeutic strategy to protect against various stresses, to
prevent several pathological conditions, and to treat chronic vascular
inflammation, such as atherosclerosis.
PMID- 28504910
TI - Fermented Moringa oleifera Decreases Hepatic Adiposity and Ameliorates Glucose
Intolerance in High-Fat Diet-Induced Obese Mice.
AB - Metabolic diseases, such as glucose intolerance and nonalcoholic fatty-liver
disease (NAFLD), are primary risk factors for life-threatening conditions such as
diabetes, heart attack, stroke, and hepatic cancer. Extracts from the tropical
tree Moringa oleifera show antidiabetic, antioxidant, anti-inflammatory, and
anticancer effects. Fermentation can further improve the safety and nutritional
value of certain foods. We investigated the efficacy of fermented M. oleifera
extract (FM) against high-fat diet (HFD)-induced glucose intolerance and hepatic
lipid accumulation and investigated the underlying mechanisms by analyzing
expression of proteins and genes involved in glucose and lipid regulation.
C57BL/6 mice were fed with normal chow diet (ND) or HFD supplemented with
distilled water (DW, control), nonfermented M. oleifera extract (NFM), or FM for
10 weeks. Although body weights were similar among HFD-fed treatment groups,
liver weight was decreased, and glucose tolerance test (GTT) results improved in
the FM group compared with DW and NFM groups. Hepatic lipid accumulation was also
lower in the FM group, and expressions of genes involved in liver lipid
metabolism were upregulated. In addition, HFD-induced endoplasmic reticulum (ER)
stress, oxidative stress, and lipotoxicity in quadriceps muscles were decreased
by FM. Finally, proinflammatory cytokine mRNA expression was decreased by FM in
the liver, epididymal adipose tissue, and quadriceps of HFD-fed mice. FMs may
decrease glucose intolerance and NAFLD under HFD-induced obesity by decreasing ER
stress, oxidative stress, and inflammation.
PMID- 28504911
TI - The Value of Sharing Information: A Neural Account of Information Transmission.
AB - Humans routinely share information with one another. What drives this behavior?
We used neuroimaging to test an account of information selection and sharing that
emphasizes inherent reward in self-reflection and connecting with other people.
Participants underwent functional MRI while they considered personally reading
and sharing New York Times articles. Activity in neural regions involved in
positive valuation, self-related processing, and taking the perspective of others
was significantly associated with decisions to select and share articles, and
scaled with preferences to do so. Activity in all three sets of regions was
greater when participants considered sharing articles with other people rather
than selecting articles to read themselves. The findings suggest that people may
consider value not only to themselves but also to others even when selecting news
articles to consume personally. Further, sharing heightens activity in these
pathways, in line with our proposal that humans derive value from self-reflection
and connecting to others via sharing.
PMID- 28504913
TI - Neurodegenerative drug discovery: building on the past, looking to the future.
PMID- 28504914
TI - G-protein-coupled receptor-based drugs rediscovered.
PMID- 28504912
TI - Synthesis and biological assessment of racemic benzochromenopyrimidinetriones as
promising agents for Alzheimer's disease therapy.
AB - AIM: Due to the complex nature of Alzheimer's disease, there is a renewed search
for multitarget directed drugs. RESULTS: This paper describes the synthesis and
in vitro biological evaluation of six racemic 13-aryl-2,3,4,13-tetrahydro-1H,12H
benzo[6,7]chromeno[2,3-d]pyrido[1,2-a]pyrimidine-7,12,14-triones (1a-6a), and six
racemic 15-aryl-8,9,10,11,12,15-hexahydro-14H-benzo[6',7']chromeno[2',3:4,5] pyr
imido [1,2-a]azepine-5,14,16-triones (1b-6b), showing antioxidant and
cholinesterase inhibitory capacity. Among these compounds, 13-phenyl-2,3,4,13
tetrahydro-1H,12H-benzo[6,7]chromeno[2,3-d]pyrido[1,2-a]pyrimidine-7,12,14-trione
(1a) is a nonhepatotoxic at 300 MUmol/l dose concentration, and a selective
EeAChE inhibitor showing good antioxidant power. CONCLUSION: A new family of
racemic benzochromenopyrimidinetriones has been investigated for their potential
use in the treatment of Alzheimer's disease.
PMID- 28504915
TI - Prevalence of Os Styloideum in National Hockey League Players.
AB - BACKGROUND: Os styloideum describes an accessory carpal ossicle between the
trapezoid, the capitate, and the second and third metacarpals. Injuries to this
tissue have been described as part of the carpal boss syndrome. While the
etiology of os styloideum remains uncertain, it may represent a physiologic
response to altered loading forces in the wrist, similar to the development of
cam-type deformity in the hips of ice hockey players or the Bennett lesion in the
shoulders of baseball pitchers. HYPOTHESIS: Professional hockey players will have
a higher prevalence of os styloideum compared with the general population. STUDY
DESIGN: Case series. LEVEL OF EVIDENCE: Level 4. METHODS: A retrospective review
of 16 professional hockey players from 4 different National Hockey League (NHL)
teams who underwent unilateral imaging of the wrist was performed. Seventeen
wrists were reviewed for the presence of os styloideum. RESULTS: Thirteen of 16
players (81%) had an os styloideum, representing an increased prevalence compared
with the general population. Previous clinical and cadaveric studies estimated a
general prevalence of up to 19% ( P < 0.001). For the 10 players who had their
leading wrist scanned, 9 had an os styloideum (90%). Ten of 11 (91%) players
demonstrated a bone marrow edema pattern within the metacarpal and the os
styloideum on magnetic resonance imaging. There was no significant association
between the presence of an os styloideum and the player's position, leading
wrist, or years in the league. CONCLUSION: There appears to be an increased
prevalence of os styloideum among NHL players, and team physicians should
consider this finding while formulating a differential diagnosis for dorsal wrist
pain. CLINICAL RELEVANCE: This study identified NHL players as having an
increased prevalence of os styloideum compared with the general population. By
doing so, these findings represent an opportunity to enhance our understanding of
the etiology, clinical significance, and treatment of os styloideum.
PMID- 28504916
TI - Contribution of Type II Topoisomerase Mutations to Fluoroquinolone Resistance in
Enterococcus faecium from Japanese Clinical Setting.
AB - High-level fluoroquinolone resistance is conferred by the mutation of conserved
serine and acidic amino acids in the quinolone resistance-determining region
(QRDR) of the A subunits of the type II topoisomerases, DNA gyrase (GyrA) and
topoisomerase IV (ParC). In Japan, fluoroquinolone-resistant Enterococcus faecium
continues to emerge in clinical settings. We analyzed 131 Japanese E. faecium
clinical isolates for susceptibility to levofloxacin (LVFX), and QRDR mutational
status. The bacterial collection had a high percentage of resistance (79%) and
showed elevated drug minimal inhibitory concentrations (MICs). Eighty-three
isolates had single or combined mutations in gyrA and/or parC; all were resistant
to LVFX. A strong correlation was evident between log-transformed MICs and the
total number of QRDR mutations (r = 0.7899), confirming the involvement of QRDR
mutations in drug resistance, as previously described. Three-dimensional modeling
indicated that the amino acid change(s) in QRDR could disrupt the interaction
between the enzymes and drugs: the most common cause of quinolone resistance.
Interestingly, eight isolates had a single mutation on gyrA and exhibited
significantly reduced susceptibility. These data imply that either DNA gyrase or
topoisomerase IV can be the primary target of fluoroquinolones, although
topoisomerase IV is commonly thought to be the primary target in gram-positive
bacteria.
PMID- 28504917
TI - Modulating 5-HT4 and 5-HT6 receptors in Alzheimer's disease treatment.
AB - Alzheimer's disease (AD) is the most common form of dementia affecting millions
of patients worldwide which can only be treated with symptomatic drugs. Among the
numbers of biological targets which are today explored in order to prevent or
limit the progression of AD, the modulation of 5-HT6R and 5-HT4R appeared to be
promising. This modulation has been proved to enhance the cognition in AD through
modulation of the neurotransmitter system but could also be beneficial in order
to limit the amyloid pathology. This review will describe recent advances in the
understanding of this modulation as well as the medicinal chemistry of 5-HT6R or
5-HT4R ligands from synthesis to ongoing clinical trials.
PMID- 28504918
TI - Sheep Placenta Cotyledons: A Noninvasive Source of Ovine Mesenchymal Stem Cells.
AB - Sheep are one of the most frequently used large animal models in stem cell
research. However, minimal invasive or noninvasive sources of mesenchymal stem
cells (MSCs) in sheep are scarce. In the light of the principles of the 3Rs
(reduce, refine, replace), it would therefore be desirable to identify a
minimally invasive or noninvasive ovine MSC source. In humans, the chorionic
villi of the placenta, which can be noninvasively harvested as part of the
afterbirth, have been identified as a rich source of MSCs. Therefore, in the
present study, ovine placenta cotyledons, which have similar function and
structure to human chorionic villi, were tested for their potential use as a
noninvasive source of ovine MSCs. Through mincing of the placental cotyledons,
collagenase digestion, and Ficoll density gradient centrifugation, combined with
plastic adherence selection, MSCs were successfully isolated. Their
morphological, immunophenotypical, and cellular growth characteristics, as well
as their proliferation, differentiation, and migration potential, were evaluated
and compared to the currently best-researched MSC source, bone marrow-derived
stem cells. Ovine cotyledons were shown to be a reliable, abundant source for the
noninvasive, pain- and risk-free harvest of MSCs. The collection procedure does
not interfere with partum or the initial bonding phase between ewes and lambs and
is therefore exempt from ethical debate. Ovine placenta cotyledon-derived MSCs
exhibit multipotential characteristics and can be cryopreserved for later use.
PMID- 28504919
TI - Does Knowing Hurt? Perceiving Oneself as Overweight Predicts Future Physical
Health and Well-Being.
AB - Identifying oneself as being overweight may be associated with adverse health
outcomes, yet prospective tests of this possibility are lacking. Over 7 years, we
examined associations between perceptions of being overweight and subsequent
health in a sample of 3,582 U.S. adults. Perceiving oneself as being overweight
predicted longitudinal declines in subjective health ( d = -0.22, p < .001),
increases in depressive symptoms ( d = 0.09, p < .05), and raised levels of
physiological dysregulation ( d = 0.24, p < .001), as gauged by clinical
indicators of cardiovascular, inflammatory, and metabolic functioning. These
associations remained after controlling for a range of potential confounders and
were observed irrespective of whether perceptions of being overweight were
accurate or inaccurate. This research highlights the possibility that identifying
oneself as overweight may act independently of body mass index to contribute to
unhealthy profiles of physiological functioning and impaired health over time.
These findings underscore the importance of evaluating whether weight-feedback
interventions may have unforeseen adverse consequences.
PMID- 28504920
TI - Silicon's Role in Abiotic and Biotic Plant Stresses.
AB - Silicon (Si) plays a pivotal role in the nutritional status of a wide variety of
monocot and dicot plant species and helps them, whether directly or indirectly,
counteract abiotic and/or biotic stresses. In general, plants with a high root or
shoot Si concentration are less prone to pest attack and exhibit enhanced
tolerance to abiotic stresses such as drought, low temperature, or metal
toxicity. However, the most remarkable effect of Si is the reduction in the
intensities of a number of seedborne, soilborne, and foliar diseases in many
economically important crops that are caused by biotrophic, hemibiotrophic, and
necrotrophic plant pathogens. The reduction in disease symptom expression is due
to the effect of Si on some components of host resistance, including incubation
period, lesion size, and lesion number. The mechanical barrier formed by the
polymerization of Si beneath the cuticle and in the cell walls was the first
proposed hypothesis to explain how this element reduced the severity of plant
diseases. However, new insights have revealed that many plant species supplied
with Si have the phenylpropanoid and terpenoid pathways potentiated and have a
faster and stronger transcription of defense genes and higher activities of
defense enzymes. Photosynthesis and the antioxidant system are also improved for
Si-supplied plants. Although the current understanding of how this overlooked
element improves plant reaction against pathogen infections, pest attacks, and
abiotic stresses has advanced, the exact mechanism(s) by which it modulates plant
physiology through the potentiation of host defense mechanisms still needs
further investigation at the genomic, metabolomic, and proteomic levels.
PMID- 28504922
TI - Abstracts: International Society for Aerosols in Medicine e.V. 21st ISAM Congress
Santa Fe, NM June 3-7, 2017.
PMID- 28504921
TI - Plasminogen Activator Inhibitor-1 and Pericardial Fat in Individuals with Type 2
Diabetes Mellitus.
AB - BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is implicated in the
pathophysiology of cardiovascular disease (CVD) and increased in individuals with
type 2 diabetes mellitus (T2DM). Adipose tissue produces PAI-1, and pericardial
fat is a CVD risk factor. We sought to determine the relationship between PAI-1
and pericardial fat in males and females with well-controlled T2DM. METHODS: The
study population consisted of 32 males and 19 females, aged 35-70 years with
T2DM, without clinical evidence of CVD or other active medical problems except
for hypertension. Subjects were studied under good cardiometabolic control. Study
procedures included fasting blood work and cardiovascular imaging. Cardiac
magnetic resonance imaging of the heart was used to identify and quantify
pericardial fat from the bifurcation of the pulmonary trunk to the last slice
containing cardiac tissue. RESULTS: PAI-1 was positively correlated with
pericardial fat (beta = 0.72, r = 0.72, P < 0.001) as well as with homeostatic
model assessment of insulin resistance (r = 0.31, P = 0.03) and serum
triglycerides (r = 0.27, P = 0.05). In a multivariable regression model,
controlling for insulin sensitivity, triglycerides, and body mass index,
pericardial fat was independently associated with PAI-1 (beta = 0.80, P < 0.001).
CONCLUSIONS: PAI-1 is positively associated with pericardial fat in individuals
with T2DM.
PMID- 28504924
TI - mRNA expression of nuclear factor of activated T-cells, cytoplasmic 2 (NFATc2)
and peroxisome proliferator-activated receptor gamma (PPARG) transcription
factors in colorectal carcinoma.
AB - Transcription factors are involved in cell cycle and apoptosis regulation and
thus have a key role in the carcinogenesis of different tumors. Nuclear factor of
activated T-cells, cytoplasmic 2 (NFATc2) and peroxisome proliferator-activated
receptor gamma (PPARG) transcription factors are important in the carcinogenesis
of colorectal cancer (CRC). In this study, we examined whether the expression of
NFATc2 and PPARG genes is significantly altered during the carcinogenesis of CRC.
A total of 47 tumor samples and matched normal tissue margins were collected
during surgery from patients with CRC. In addition, three CRC cell lines (HCT119,
SW480, and HT29) and healthy cell line were used. After total RNA extraction and
cDNA synthesis, mRNA expression levels of NFATc2 and PPARG were examined by real
time polymerase chain reaction. The results showed that NFATc2 is overexpressed
in the tumor tissues compared with normal tissue margins (p <= 0.05). However,
the mRNA expression levels of PPARG were not significantly different between the
tumor tissues and tissue margins. Our results indicate that NFATc2 may be used as
an early diagnostic or predictive biomarker for CRC as well as a therapeutic
target, providing that upcoming studies confirm these results.
PMID- 28504926
TI - Accurate differentiation of Mycobacterium chimaera from Mycobacterium
intracellulare by MALDI-TOF MS analysis.
AB - PURPOSE: The increasing number of infections caused by nontuberculous
mycobacteria (NTM) has prompted the need for rapid and precise identification
methods of these pathogens. Several studies report the applicability of MALDI-TOF
mass spectrometry (MS) for identification of NTM. However, some closely related
species have very similar spectral mass fingerprints, and until recently,
Mycobacterium chimaera and M. intracellulare could not be separated from each
other by MALDI-TOF MS. METHODOLOGY: The conventional identification methods used
in routine diagnostics have similar limitations. Recently, the differentiation of
these two species within the Mycobacterium avium complex has become increasingly
important due to reports of M. chimaera infections related to open heart surgery
in Europe and in the USA. In this report, a method for the distinct
differentiation of M. chimaera and M. intracellulare using a more detailed
analysis of MALDI-TOF mass spectra is presented. KEY FINDINGS: Species-specific
peaks could be identified and it was possible to assign all isolates (100 %) from
reference strain collections as well as clinical isolates to the correct species.
CONCLUSIONS: We have developed a model for the accurate identification of M.
chimaera and M. intracellulare by MALDI-TOF MS. This approach has the potential
for routine use in microbiology laboratories, as the model itself can be easily
implemented into the software of the currently available systems by MALDI-TOF MS
manufacturers.
PMID- 28504925
TI - Comparative diagnostic test evaluation of serum procalcitonin and C-reactive
protein in suspected bloodstream infections in children with cancer.
AB - PURPOSE: To compute diagnostic test properties of C-reactive protein (CRP) and
serum procalcitonin (PCT) levels in bloodstream infections in children with
cancer and suspected sepsis, in comparison with blood culture as the gold
standard. METHODOLOGY: Consecutive paediatric cancer patients, aged <=14 years,
with clinically suspected bloodstream infections were evaluated with blood
culture and assay of PCT and CRP levels. Blood culture was taken as the gold
standard for comparison. Sensitivity, specificity, positive predictive value
(PPV), negative predictive value (NPV), likelihood ratio (LR) and receiver
operating characteristic (ROC) with area under ROC curve (AUC) were calculated to
assess the diagnostic test performance for PCT and CRP.Results/Key findings. The
ROC curve for PCT was better than that for CRP, with an AUC of 0.751 for PCT at a
cut-off of 2.25 ng ml-1. The AUC for CRP was 0.638 at a cut-off of 8.0 mg dl-1.
Among the three cut-off values of PCT selected from the ROC curve applicable to
the patients under study, the cut-off value of >=0.49 ng ml-1 had the maximum
sensitivity of 81.4 % and an NPV of 94.67 %; >=2.25 ng ml-1 had a sensitivity and
specificity of 65.12 and 71.6 %, respectively, and >=6.47 ng ml-1 had a maximum
specificity of 82.10 %. For CRP, the cut-off value of >=5.3 mg dl-1 had the
maximum sensitivity of 72.09 %; >=8.0 mg dl-1 had a sensitivity and specificity
of 58.14 and 68.09 %, respectively, and >=8.4 mg dl-1 had the maximum specificity
of 70.04 %. CONCLUSION: PCT is a better serological marker for excluding
bloodstream infections than CRP. The cut-off value of 0.49 ng ml-1 with a
negative predictive value of 94.67 % will be ideal in a clinical setting of
immune-compromised children with suspected sepsis.
PMID- 28504927
TI - Mechanisms of quinolone action and resistance: where do we stand?
AB - Quinolone antibiotics represent one of the most important classes of anti
infective agents and, although still clinically valuable, their use has been
compromised by the increasing emergence of resistant strains, which has become a
prevalent clinical problem. Quinolones act by inhibiting the activity of DNA
gyrase and topoisomerase IV - two essential bacterial enzymes that modulate the
chromosomal supercoiling required for critical nucleic acid processes. The
acquisition of quinolone resistance is recognized to be multifactorial and
complex. The main resistance mechanism consists of one or a combination of target
site gene mutations that alter the drug-binding affinity of target enzymes.
However, other mechanisms such as mutations that lead to reduced intracellular
drug concentrations, by either decreased uptake or increased efflux, and plasmid
encoded resistance genes producing either target protection proteins, drug
modifying enzymes or multidrug efflux pumps are known to contribute additively to
quinolone resistance. The understanding of these different resistance mechanisms
has improved significantly in recent years; however, many details remain to be
clarified and the contribution of less-studied mechanisms still needs to be
better elucidated in order to fully understand this phenotype.
PMID- 28504930
TI - Extracorporeal Stimulation of Sacral Nerve Roots for Observation of Pelvic
Autonomic Nerve Integrity: Description of a Novel Methodological Setup.
AB - INTRODUCTION: Neurophysiologic monitoring can improve autonomic nerve sparing
during critical phases of rectal cancer surgery. OBJECTIVES: To develop a system
for extracorporeal stimulation of sacral nerve roots. METHODS: Dedicated software
controlled a ten-electrode stimulation array by switching between different
electrode configurations and current levels. A built-in impedance and current
level measurement assessed the effectiveness of current injection. Intra-anal
surface electromyography (sEMG) informed on targeting the sacral nerve roots. All
tests were performed on five pig specimens. RESULTS: During switching between
electrode configurations, the system delivered 100% of the set current (25 mA, 30
Hz, 200 MUs cathodic pulses) in 93% of 250 stimulation trains across all
specimens. The impedance measured between single stimulation array contacts and
corresponding anodes across all electrode configurations and specimens equaled
3.7 +/- 2.5 kOmega. The intra-anal sEMG recorded a signal amplitude increase as
previously observed in the literature. When the stimulation amplitude was tested
in the range from 1 to 21 mA using the interconnected contacts of the stimulation
array and the intra-anal anode, the impedance remained below 250 Omega and the
system delivered 100% of the set current in all cases. Intra-anal sEMG showed an
amplitude increase for current levels exceeding 6 mA. CONCLUSION: The system
delivered stable electric current, which was proved by built-in impedance and
current level measurements. Intra-anal sEMG confirmed the ability to target the
branches of the autonomous nervous system originating from the sacral nerve
roots. SIGNIFICANCE: Stimulation outside of the operative field during rectal
cancer surgery is feasible and may improve the practicality of pelvic
intraoperative neuromonitoring.
PMID- 28504931
TI - Robust Real-Time Musculoskeletal Modeling Driven by Electromyograms.
AB - OBJECTIVE: Current clinical biomechanics involves lengthy data acquisition and
time-consuming offline analyses with biomechanical models not operating in real
time for man-machine interfacing. We developed a method that enables online
analysis of neuromusculoskeletal function in vivo in the intact human. METHODS:
We used electromyography (EMG)-driven musculoskeletal modeling to simulate all
transformations from muscle excitation onset (EMGs) to mechanical moment
production around multiple lower-limb degrees of freedom (DOFs). We developed a
calibration algorithm that enables adjusting musculoskeletal model parameters
specifically to an individual's anthropometry and force-generating capacity. We
incorporated the modeling paradigm into a computationally efficient, generic
framework that can be interfaced in real-time with any movement data collection
system. RESULTS: The framework demonstrated the ability of computing forces in 13
lower-limb muscle-tendon units and resulting moments about three joint DOFs
simultaneously in real-time. Remarkably, it was capable of extrapolating beyond
calibration conditions, i.e., predicting accurate joint moments during six unseen
tasks and one unseen DOF. CONCLUSION: The proposed framework can dramatically
reduce evaluation latency in current clinical biomechanics and open up new
avenues for establishing prompt and personalized treatments, as well as for
establishing natural interfaces between patients and rehabilitation systems.
SIGNIFICANCE: The integration of EMG with numerical modeling will enable
simulating realistic neuromuscular strategies in conditions including
muscular/orthopedic deficit, which could not be robustly simulated via pure
modeling formulations. This will enable translation to clinical settings and
development of healthcare technologies including real-time bio-feedback of
internal mechanical forces and direct patient-machine interfacing.
PMID- 28504932
TI - Generalizing Pooling Functions in CNNs: Mixed, Gated, and Tree.
AB - In this paper, we seek to improve deep neural networks by generalizing the
pooling operations that play a central role in the current architectures. We
pursue a careful exploration of approaches to allow pooling to learn and to adapt
to complex and variable patterns. The two primary directions lie in: (1) learning
a pooling function via (two strategies of) combining of max and average pooling,
and (2) learning a pooling function in the form of a tree-structured fusion of
pooling filters that are themselves learned. In our experiments every generalized
pooling operation we explore improves performance when used in place of average
or max pooling. We experimentally demonstrate that the proposed pooling
operations provide a boost in invariance properties relative to conventional
pooling and set the state of the art on several widely adopted benchmark
datasets. These benefits come with only a light increase in computational
overhead during training (ranging from additional 5 to 15 percent in time
complexity) and a very modest increase in the number of model parameters (e.g.,
additional 1, 9, and 27 parameters for mixed, gated, and 2-level tree pooling
operators, respectively). To gain more insights about our proposed pooling
methods, we also visualize the learned pooling masks and the embeddings of the
internal feature responses for different pooling operations. Our proposed pooling
operations are easy to implement and can be applied within various deep neural
network architectures.
PMID- 28504933
TI - A Novel Linelet-Based Representation for Line Segment Detection.
AB - This paper proposes a method for line segment detection in digital images. We
propose a novel linelet-based representation to model intrinsic properties of
line segments in rasterized image space. Based on this, line segment detection,
validation, and aggregation frameworks are constructed. For a numerical
evaluation on real images, we propose a new benchmark dataset of real images with
annotated lines called YorkUrban-LineSegment. The results show that the proposed
method outperforms state-of-the-art methods numerically and visually. To our best
knowledge, this is the first report of numerical evaluation of line segment
detection on real images.
PMID- 28504928
TI - The murine catecholamine methyltransferase mTOMT is essential for
mechanotransduction by cochlear hair cells.
AB - Hair cells of the cochlea are mechanosensors for the perception of sound.
Mutations in the LRTOMT gene, which encodes a protein with homology to the
catecholamine methyltransferase COMT that is linked to schizophrenia, cause
deafness. Here, we show that Tomt/Comt2, the murine ortholog of LRTOMT, has an
unexpected function in the regulation of mechanotransduction by hair cells. The
role of mTOMT in hair cells is independent of mTOMT methyltransferase function
and mCOMT cannot substitute for mTOMT function. Instead, mTOMT binds to putative
components of the mechanotransduction channel in hair cells and is essential for
the transport of some of these components into the mechanically sensitive
stereocilia of hair cells. Our studies thus suggest functional diversification
between mCOMT and mTOMT, where mTOMT is critical for the assembly of the
mechanotransduction machinery of hair cells. Defects in this process are likely
mechanistically linked to deafness caused by mutations in LRTOMT/Tomt.
PMID- 28504929
TI - Evolution of an intricate J-protein network driving protein disaggregation in
eukaryotes.
AB - Hsp70 participates in a broad spectrum of protein folding processes extending
from nascent chain folding to protein disaggregation. This versatility in
function is achieved through a diverse family of J-protein cochaperones that
select substrates for Hsp70. Substrate selection is further tuned by transient
complexation between different classes of J-proteins, which expands the range of
protein aggregates targeted by metazoan Hsp70 for disaggregation. We assessed the
prevalence and evolutionary conservation of J-protein complexation and
cooperation in disaggregation. We find the emergence of a eukaryote-specific
signature for interclass complexation of canonical J-proteins. Consistently,
complexes exist in yeast and human cells, but not in bacteria, and correlate with
cooperative action in disaggregation in vitro. Signature alterations exclude some
J-proteins from networking, which ensures correct J-protein pairing, functional
network integrity and J-protein specialization. This fundamental change in J
protein biology during the prokaryote-to-eukaryote transition allows for
increased fine-tuning and broadening of Hsp70 function in eukaryotes.
PMID- 28504934
TI - Vision-Based Surgical Field Defogging.
AB - Fogged surgical field visualization that is a common and potentially harmful
problem can lead to inappropriate device use and incorrectly targeted tissue and
increase surgical risks in endoscopic surgery. This paper aims to remove fog or
smoke on endoscopic video sequences to augment and maintain a direct and clear
visualization of the operating field. A new visibility-driven fusion defogging
framework is proposed for surgical endoscopic video processing. This framework
first recovers the visibility and enhances the contrast of hazy images. To
address the color infidelity problem introduced by the visibility recovery, the
luminances of the recovered and enhanced images are fused in the gradient domain,
and the fused luminance is reconstructed by solving the Poisson equation in the
frequency domain. The proposed method is evaluated on clinical videos that were
collected from prostate cancer surgery. The experimental results demonstrate that
the proposed framework defogs endoscopic images more robustly than currently
available methods. Additionally, our method also provides an effective way to
improve the visual quality of medical or high-dynamic range images.
PMID- 28504935
TI - Efficient 3-D Model-Based Reconstruction Scheme for Arbitrary Optoacoustic
Acquisition Geometries.
AB - Optimal optoacoustic tomographic sampling is often hindered by the frequency
dependent directivity of ultrasound sensors, which can only be accounted for with
an accurate 3-D model. Herein, we introduce a 3-D model-based reconstruction
method applicable to optoacoustic imaging systems employing detection elements
with arbitrary size and shape. The computational complexity and memory
requirements are mitigated by introducing an efficient graphic processing unit
(GPU)-based implementation of the iterative inversion. On-the-fly calculation of
the entries of the model-matrix via a small look-up table avoids otherwise
unfeasible storage of matrices typically occupying more than 300GB of memory.
Superior imaging performance of the suggested method with respect to standard
optoacoustic image reconstruction methods is first validated quantitatively using
tissue-mimicking phantoms. Significant improvements in the spatial resolution,
contrast to noise ratio and overall 3-D image quality are also reported in real
tissues by imaging the finger of a healthy volunteer with a hand-held volumetric
optoacoustic imaging system.
PMID- 28504936
TI - Wave Mode Discrimination of Coded Ultrasonic Guided Waves Using Two-Dimensional
Compressed Pulse Analysis.
AB - Ultrasonic guided waves testing is a technique successfully used in many
industrial scenarios worldwide. For many complex applications, the dispersive
nature and multimode behavior of the technique still poses a challenge for
correct defect detection capabilities. In order to improve the performance of the
guided waves, a 2-D compressed pulse analysis is presented in this paper. This
novel technique combines the use of pulse compression and dispersion compensation
in order to improve the signal-to-noise ratio (SNR) and temporal-spatial
resolution of the signals. The ability of the technique to discriminate different
wave modes is also highlighted. In addition, an iterative algorithm is developed
to identify the wave modes of interest using adaptive peak detection to enable
automatic wave mode discrimination. The employed algorithm is developed in order
to pave the way for further in situ applications. The performance of Barker-coded
and chirp waveforms is studied in a multimodal scenario where longitudinal and
flexural wave packets are superposed. The technique is tested in both synthetic
and experimental conditions. The enhancements in SNR and temporal resolution are
quantified as well as their ability to accurately calculate the propagation
distance for different wave modes.
PMID- 28504937
TI - Ultrasonic Fingerprint Sensor With Transmit Beamforming Based on a PMUT Array
Bonded to CMOS Circuitry.
AB - In this paper, we present a single-chip 65 *42 element ultrasonic pulse-echo
fingerprint sensor with transmit (TX) beamforming based on piezoelectric
micromachined ultrasonic transducers directly bonded to a CMOS readout
application-specific integrated circuit (ASIC). The readout ASIC was realized in
a standard 180-nm CMOS process with a 24-V high-voltage transistor option. Pulse
echo measurements are performed column-by-column in sequence using either one
column or five columns to TX the ultrasonic pulse at 20 MHz. TX beamforming is
used to focus the ultrasonic beam at the imaging plane where the finger is
located, increasing the ultrasonic pressure and narrowing the 3-dB beamwidth to
[Formula: see text], a factor of 6.4 narrower than nonbeamformed measurements.
The surface of the sensor is coated with a poly-dimethylsiloxane (PDMS) layer to
provide good acoustic impedance matching to skin. Scanning laser Doppler
vibrometry of the PDMS surface was used to map the ultrasonic pressure field at
the imaging surface, demonstrating the expected increase in pressure, and
reduction in beamwidth. Imaging experiments were conducted using both PDMS
phantoms and real fingerprints. The average image contrast is increased by a
factor of 1.5 when beamforming is used.
PMID- 28504938
TI - Perceptual Real-Time 2D-to-3D Conversion Using Cue Fusion.
AB - We propose a system to infer binocular disparity from a monocular video stream in
real-time. Different from classic reconstruction of physical depth in computer
vision, we compute perceptually plausible disparity, that is numerically
inaccurate, but results in a very similar overall depth impression with plausible
overall layout, sharp edges, fine details and agreement between luminance and
disparity. We use several simple monocular cues to estimate disparity maps and
confidence maps of low spatial and temporal resolution in real-time. These are
complemented by spatially-varying, appearance-dependent and class-specific
disparity prior maps, learned from example stereo images. Scene classification
selects this prior at runtime. Fusion of prior and cues is done by means of
robust MAP inference on a dense spatio-temporal conditional random field with
high spatial and temporal resolution. Using normal distributions allows this in
constant-time, parallel per-pixel work. We compare our approach to previous 2D-to
3D conversion systems in terms of different metrics, as well as a user study and
validate our notion of perceptually plausible disparity.
PMID- 28504939
TI - Correlation-Preserving Photo Collage.
AB - A new method is presented for producing photo collages that preserve content
correlation of photos. We use deep learning techniques to find correlation among
given photos to facilitate their embedding on the canvas, and develop an
efficient combinatorial optimization technique to make correlated photos stay
close to each other. To make efficient use of canvas space, our method first
extracts salient regions of photos and packs only these salient regions. We allow
the salient regions to have arbitrary shapes, therefore yielding informative, yet
more compact collages than by other similar collage methods based on salient
regions. We present extensive experimental results, user study results, and
comparisons against the state-of-the-art methods to show the superiority of our
method.
PMID- 28504940
TI - Good Random Multi-Triangulation of Surfaces.
AB - We introduce the Hierarchical Poisson Disk Sampling Multi-Triangulation (HPDS-MT)
of surfaces, a novel structure that combines the power of multi-triangulation
(MT) with the benefits of Hierarchical Poisson Disk Sampling (HPDS). MT is a
general framework for representing surfaces through variable resolution triangle
meshes, while HPDS is a well-spaced random distribution with blue noise
characteristics. The distinguishing feature of the HPDS-MT is its ability to
extract adaptive meshes whose triangles are guaranteed to have good shape
quality. The key idea behind the HPDS-MT is a preprocessed hierarchy of points,
which is used in the construction of a MT via incremental simplification. In
addition to proving theoretical properties on the shape quality of the triangle
meshes extracted by the HPDS-MT, we provide an implementation that computes the
HPDS-MT with high accuracy. Our results confirm the theoretical guarantees and
outperform similar methods. We also prove that the Hausdorff distance between the
original surface and any (extracted) adaptive mesh is bounded by the sampling
distribution of the radii of Poisson-disks over the surface. Finally, we
illustrate the advantages of the HPDS-MT in some typical problems of geometry
processing.
PMID- 28504941
TI - Advanced Hierarchical Spherical Parameterizations.
AB - Computing spherical parameterizations for genus-zero closed surfaces is a
fundamental task for geometric processing and computer graphics. Existing methods
usually suffer from a lack of practical robustness or poor quality. In this
paper, we present a practically robust method to compute high-quality spherical
parameterizations with bijection and low isometric distortion. Our method is
based on the hierarchical scheme containing mesh decimation and parameterization
refinement. The practical robustness of our method relies on two novel
techniques. The first one is a flat-to-extrusive decimation strategy, which
contains two decimation error metrics to alleviate the difficulty of further mesh
refinement. The second is a flexible group refinement technique that consists of
flexible vertex insertion and efficient volumetric distortion minimization to
control the maximum distortion. We convert the task of volumetric distortion
minimization to one of tetrahedral mesh improvement to make the vertices
distribute uniformly for efficient refinement. Compared with state-of-the-art
methods, our method is more practically robust and possesses better mapping
qualities. We demonstrate the efficacy of our method in spherical
parameterization computations on a data set containing over five thousand complex
models.
PMID- 28504942
TI - Interaction of Perceived Frequency and Intensity in Fingertip Electrotactile
Stimulation: Dissimilarity Ratings and Multidimensional Scaling.
AB - Sensations elicited by electrical stimulation of touch are multidimensional,
varying in perceived intensity and quality in response to changes in stimulus
current or waveform timing. This paper manipulated both current and frequency,
while volunteer participants estimated the dissimilarity of all non-identical
pairs of 16 stimulus conditions. Multidimensional scaling analysis revealed that
a model having two perceptual dimensions was adequate in representing the
electrotactile (electrocutaneous) sensations. The two dimensions were identified
as perceptual frequency and intensity, and were strongly correlated with the two
stimulus variables, frequency and current, although not in a 1:1 correspondence.
Perception of frequency differences increased monotonically with stimulus
intensity, which is consistent with other human sensory systems, such as hearing
and vision. Our results are consistent with previously-reported research using a
different methodology and cutaneous locus. Congruence across different methods
and laboratories suggests similar underlying perceptual mechanisms.
PMID- 28504943
TI - Toward Multimodal Human-Robot Interaction to Enhance Active Participation of
Users in Gait Rehabilitation.
AB - Robotic exoskeletons for physical rehabilitation have been utilized for
retraining patients suffering from paraplegia and enhancing motor recovery in
recent years. However, users are not voluntarily involved in most systems. This
paper aims to develop a locomotion trainer with multiple gait patterns, which can
be controlled by the active motion intention of users. A multimodal human-robot
interaction (HRI) system is established to enhance subject's active participation
during gait rehabilitation, which includes cognitive HRI (cHRI) and physical HRI
(pHRI). The cHRI adopts brain-computer interface based on steady-state visual
evoked potential. The pHRI is realized via admittance control based on
electromyography. A central pattern generator is utilized to produce rhythmic and
continuous lower joint trajectories, and its state variables are regulated by
cHRI and pHRI. A custom-made leg exoskeleton prototype with the proposed
multimodal HRI is tested on healthy subjects and stroke patients. The results
show that voluntary and active participation can be effectively involved to
achieve various assistive gait patterns.
PMID- 28504944
TI - Perspective: It's All About Time.
AB - New knowledge on multi-scale temporal dynamics linking nanobio-time series,
seasonal changes, immune response, and gut mictobiota can milestone (neuro)
science soon.
PMID- 28504945
TI - A Bio-Inspired Hybrid Thermal Management Approach for 3-D Network-on-Chip
Systems.
AB - 3-D network-on-chip (NoC) systems are getting popular among the integrated
circuit (IC) manufacturer because of reduced latency, heterogeneous integration
of technologies on a single chip, high yield, and consumption of less
interconnecting power. However, the addition of functional units in the
direction has resulted in higher on-chip temperature and appearance of local
hotspots on the die. The increase in temperature degrades the performance,
lifetime, and reliability, and increases the maintenance cost of 3-D ICs. To keep
the heat within an acceptable limit, floorplanning is the widely accepted
solution. Proper arrangement of functional units across different layers can lead
to uniform thermal distribution in the chip. For systems with high density of
elements, few hotspots cannot be eliminated in the floorplanning approach. To
overcome, liquid microchannel cooling technology has emerged as an efficient and
scalable solution for 3-D NoC. In this paper, we propose a novel hybrid algorithm
combining both floorplanning, and liquid microchannel placement to alleviate the
hotspots in high-density systems. A mathematical model is proposed to deal with
heat transfer due to diffusion and convention. The proposed approach is
independent of topology. Three different topologies: 3-D stacked homogeneous mesh
architecture, 3-D stacked heterogeneous mesh architecture, and 3-D stacked
ciliated mesh architecture are considered to check the effectiveness of the
proposed algorithm in hotspot reduction. A thermal comparison is made with and
without the proposed thermal management approach for the above architectures
considered. It is observed that there is a significant reduction in on-chip
temperature when the proposed thermal management approach is applied.
PMID- 28504946
TI - Essential Protein Detection by Random Walk on Weighted Protein-Protein
Interaction Networks.
AB - Essential proteins are critical to the development and survival of cells.
Identification of essential proteins is helpful for understanding the minimal set
of required genes in a living cell and for designing new drugs. To detect
essential proteins, various computational methods have been proposed based on
protein-protein interaction (PPI) networks. However, protein interaction data
obtained by highthroughput experiments usually contain high false positives,
which negatively impacts the accuracy of essential protein detection. Moreover,
most existing studies focused on the local information of proteins in PPI
networks, while ignoring the influence of indirect protein interactions on
essentiality. In this paper, we propose a novel method, called Essentiality
Ranking (EssRank in short), to boost the accuracy of essential protein detection.
To deal with the inaccuracy of PPI data, confidence scores of interactions are
evaluated by integrating various biological information. Weighted edge clustering
coefficient (WECC), considering both interaction confidence scores and network
topology, is proposed to calculate edge weights in PPI networks. The weight of
each node is evaluated by the sum of WECC values of its linking edges. A random
walk method, making use of both direct and indirect protein interactions, is then
employed to calculate protein essentiality iteratively. Experimental results on
the yeast PPI network show that EssRank outperforms most existing methods,
including the most commonly-used centrality measures (SC, DC, BC, CC, IC, EC),
topology based methods (DMNC and NC) and the data integrating method IEW.
PMID- 28504947
TI - Robust Wireless Power Transmission to mm-Sized Free-Floating Distributed
Implants.
AB - This paper presents an inductive link for wireless power transmission (WPT) to mm
sized free-floating implants (FFIs) distributed in a large three-dimensional
space in the neural tissue that is insensitive to the exact location of the
receiver (Rx). The proposed structure utilizes a high-Q resonator on the target
wirelessly powered plane that encompasses randomly positioned multiple FFIs, all
powered by a large external transmitter (Tx). Based on resonant WPT fundamentals,
we have devised a detailed method for optimization of the FFIs and explored
design strategies and safety concerns, such as coil segmentation and specific
absorption rate limits using realistic finite element simulation models in HFSS
including head tissue layers, respectively. We have built several FFI prototypes
to conduct accurate measurements and to characterize the performance of the
proposed WPT method. Measurement results on 1-mm receivers operating at 60 MHz
show power transfer efficiency and power delivered to the load at 2.4% and 1.3
mW, respectively, within 14-18 mm of Tx-Rx separation and 7 cm2 of brain surface.
PMID- 28504948
TI - Substructural Regularization With Data-Sensitive Granularity for Sequence
Transfer Learning.
AB - Sequence transfer learning is of interest in both academia and industry with the
emergence of numerous new text domains from Twitter and other social media tools.
In this paper, we put forward the data-sensitive granularity for transfer
learning, and then, a novel substructural regularization transfer learning model
(STLM) is proposed to preserve target domain features at substructural
granularity in the light of the condition of labeled data set size. Our model is
underpinned by hidden Markov model and regularization theory, where the
substructural representation can be integrated as a penalty after measuring the
dissimilarity of substructures between target domain and STLM with relative
entropy. STLM can achieve the competing goals of preserving the target domain
substructure and utilizing the observations from both the target and source
domains simultaneously. The estimation of STLM is very efficient since an
analytical solution can be derived as a necessary and sufficient condition. The
relative usability of substructures to act as regularization parameters and the
time complexity of STLM are also analyzed and discussed. Comprehensive
experiments of part-of-speech tagging with both Brown and Twitter corpora fully
justify that our model can make improvements on all the combinations of source
and target domains.
PMID- 28504949
TI - Cascaded Subpatch Networks for Effective CNNs.
AB - Conventional convolutional neural networks use either a linear or a nonlinear
filter to extract features from an image patch (region) of spatial size
(typically, is small and is equal to , e.g., is 5 or 7). Generally, the size of
the filter is equal to the size of the input patch. We argue that the
representational ability of equal-size strategy is not strong enough. To overcome
the drawback, we propose to use subpatch filter whose spatial size is smaller
than . The proposed subpatch filter consists of two subsequent filters. The first
one is a linear filter of spatial size and is aimed at extracting features from
spatial domain. The second one is of spatial size and is used for strengthening
the connection between different input feature channels and for reducing the
number of parameters. The subpatch filter convolves with the input patch and the
resulting network is called a subpatch network. Taking the output of one subpatch
network as input, we further repeat constructing subpatch networks until the
output contains only one neuron in spatial domain. These subpatch networks form a
new network called the cascaded subpatch network (CSNet). The feature layer
generated by CSNet is called the csconv layer. For the whole input image, we
construct a deep neural network by stacking a sequence of csconv layers.
Experimental results on five benchmark data sets demonstrate the effectiveness
and compactness of the proposed CSNet. For example, our CSNet reaches a test
error of 5.68% on the CIFAR10 data set without model averaging. To the best of
our knowledge, this is the best result ever obtained on the CIFAR10 data set.
PMID- 28504950
TI - Graph Regularized Restricted Boltzmann Machine.
AB - The restricted Boltzmann machine (RBM) has received an increasing amount of
interest in recent years. It determines good mapping weights that capture useful
latent features in an unsupervised manner. The RBM and its generalizations have
been successfully applied to a variety of image classification and speech
recognition tasks. However, most of the existing RBM-based models disregard the
preservation of the data manifold structure. In many real applications, the data
generally reside on a low-dimensional manifold embedded in high-dimensional
ambient space. In this brief, we propose a novel graph regularized RBM to capture
features and learning representations, explicitly considering the local manifold
structure of the data. By imposing manifold-based locality that preserves
constraints on the hidden layer of the RBM, the model ultimately learns sparse
and discriminative representations. The representations can reflect data
distributions while simultaneously preserving the local manifold structure of
data. We test our model using several benchmark image data sets for unsupervised
clustering and supervised classification problem. The results demonstrate that
the performance of our method exceeds the state-of-the-art alternatives.
PMID- 28504951
TI - A Sequential Learning Approach for Scaling Up Filter-Based Feature Subset
Selection.
AB - Increasingly, many machine learning applications are now associated with very
large data sets whose sizes were almost unimaginable just a short time ago. As a
result, many of the current algorithms cannot handle, or do not scale to, today's
extremely large volumes of data. Fortunately, not all features that make up a
typical data set carry information that is relevant or useful for prediction, and
identifying and removing such irrelevant features can significantly reduce the
total data size. The unfortunate dilemma, however, is that some of the current
data sets are so large that common feature selection algorithms-whose very goal
is to reduce the dimensionality-cannot handle such large data sets, creating a
vicious cycle. We describe a sequential learning framework for feature subset
selection (SLSS) that can scale with both the number of features and the number
of observations. The proposed framework uses multiarm bandit algorithms to
sequentially search a subset of variables, and assign a level of importance for
each feature. The novel contribution of SLSS is its ability to naturally scale to
large data sets, evaluate such data in a very small amount of time, and be
performed independently of the optimization of any classifier to reduce
unnecessary complexity. We demonstrate the capabilities of SLSS on synthetic and
real-world data sets.
PMID- 28504952
TI - Exponential Synchronization of Networked Chaotic Delayed Neural Network by a
Hybrid Event Trigger Scheme.
AB - This paper is concerned with the exponential synchronization for master-slave
chaotic delayed neural network with event trigger control scheme. The model is
established on a network control framework, where both external disturbance and
network-induced delay are taken into consideration. The desired aim is to
synchronize the master and slave systems with limited communication capacity and
network bandwidth. In order to save the network resource, we adopt a hybrid event
trigger approach, which not only reduces the data package sending out, but also
gets rid of the Zeno phenomenon. By using an appropriate Lyapunov functional, a
sufficient criterion for the stability is proposed for the error system with
extended ( , , )-dissipativity performance index. Moreover, hybrid event trigger
scheme and controller are codesigned for network-based delayed neural network to
guarantee the exponential synchronization between the master and slave systems.
The effectiveness and potential of the proposed results are demonstrated through
a numerical example.
PMID- 28504953
TI - Adaptive Seizure Onset Detection Framework Using a Hybrid PCA-CSP Approach.
AB - Epilepsy is one of the most common neurological disorders in the world. Prompt
detection of seizure onset from electroencephalogram (EEG) signals can improve
the treatment of epileptic patients. This paper presents a new adaptive patient
specific seizure onset detection framework that dynamically selects a feature
from enhanced EEG signals to discriminate seizures from normal brain activity.
The proposed framework employs principal component analysis and common spatial
patterns to enhance the EEG signals and uses the extracted discriminative feature
as an input for adaptive distance-based change point detector to identify the
seizure onsets. Experimental results from the Children's Hospital Boston
Massachusetts Institute of Technology (CHB-MIT) dataset show the computational
efficiency of the proposed method (analyzing EEG signals in a time window of 3 s
within 0.1 s using a Core i7 PC) while providing comparable results to the
existing methods in terms of average sensitivity, latency, and false detection
rate. The proposed method is advantageous for real-time monitoring of epileptic
patients and could be used to improve early diagnosis and treatment of patients
suffering from recurrent seizures.
PMID- 28504954
TI - Automatic Fetal Head Circumference Measurement in Ultrasound Using Random Forest
and Fast Ellipse Fitting.
AB - Head circumference (HC) is one of the most important biometrics in assessing
fetal growth during prenatal ultrasound examinations. However, the manual
measurement of this biometric by doctors often requires substantial experience.
We developed a learning-based framework that used prior knowledge and employed a
fast ellipse fitting method (ElliFit) to measure HC automatically. We first
integrated the prior knowledge about the gestational age and ultrasound scanning
depth into a random forest classifier to localize the fetal head. We further used
phase symmetry to detect the center line of the fetal skull and employed ElliFit
to fit the HC ellipse for measurement. The experimental results from 145 HC
images showed that our method had an average measurement error of 1.7 mm and
outperformed traditional methods. The experimental results demonstrated that our
method shows great promise for applications in clinical practice.
PMID- 28504955
TI - Three-Dimensional Intravascular Reconstruction Techniques Based on Intravascular
Ultrasound: A Technical Review.
AB - Intravascular ultrasound (IVUS) imaging provides two-dimensional (2-D) real-time
luminal and transmural cross-sectional images of intravascular vessels with
detailed pathological information. It has offered significant advantages in terms
of diagnosis and guidance and has been increasingly introduced from coronary
interventions into more generalized endovascular surgery. However, IVUS itself
does not provide spatial pose information for its generated images, making it
difficult to construct a 3-D intravascular visualization. To address this
limitation, IVUS imaging-driven 3-D intravascular reconstruction techniques have
been developed. These techniques enable accurate diagnosis and quantitative
measurements of intravascular diseases to facilitate optimal treatment
determination. Such reconstruction extends the IVUS imaging modality from pure
diagnostic assistance to intraoperative navigation and guidance and supports both
therapeutic options and interventional operations. This paper presents a
comprehensive survey of technological advances and recent progress on IVUS
imaging-based 3-D intravascular reconstruction and its state-of-the-art
applications. Limitations of existing technologies and prospects of new
technologies are also discussed.
PMID- 28504965
TI - HDAC/IKK inhibition therapies in solid tumors.
PMID- 28504966
TI - Functional characterization of the lysosomal membrane protein TMEM192 in mice.
AB - The Transmembrane protein 192 (TMEM192) is a lysosomal/late endosomal protein
initially discovered by organellar proteomics. TMEM192 exhibits four
transmembrane segments with cytosolic N- and C-termini and forms homodimers.
Devoid of significant homologies, the molecular function of TMEM192 is currently
unknown. Upon TMEM192 knockdown in hepatoma cells, a dysregulation of autophagy
and increased apoptosis were reported. Here, we aimed to define the physiological
role of TMEM192 by analysing consequences of TMEM192 ablation in mice. Therefore,
we compared the biochemical properties of murine TMEM192 to those of the human
orthologue. We reveal lysosomal residence of murine TMEM192 and demonstrate
ubiquitous tissue expression. In brain, TMEM192 expression was pronounced in the
hippocampus but also present in the cortex and cerebellum, as analysed based on a
lacZ reporter allele. Murine TMEM192 undergoes proteolytic processing in a tissue
specific manner. Thereby, a 17 kDa fragment is generated which was detected in
most murine tissues except liver. TMEM192 processing occurs after lysosomal
targeting by pH-dependent lysosomal proteases. TMEM192-/- murine embryonic
fibroblasts (MEFs) exhibited a regular morphology of endo-/lysosomes and were
capable of performing autophagy and lysosomal exocytosis. Histopathological,
ultrastructural and biochemical analyses of all major tissues of TMEM192-/- mice
demonstrated normal lysosomal functions without apparent lysosomal storage.
Furthermore, the abundance of the major immune cells was comparable in TMEM192-/-
and wild type mice. Based on this, we conclude that under basal conditions in
vivo the loss of TMEM192 can be efficiently compensated by alternative pathways.
Further studies will be required to decipher its molecular function.
PMID- 28504972
TI - Temperature dependent spectroscopic and excited state dynamics of 3
hydroxychromones with electron donor and acceptor substituents.
AB - We have studied the photophysical and photochemical behavior of three compounds
derived from 3-hydroxychromone (3-HC), capable of undergoing excited state proton
transfer (ESIPT). The compounds have two substituents, located in positions 2 and
7, one on each ring of the 3-HC heterocycle. The substituent pattern shows
different electron donating and acceptor features. The compounds were studied by
absorption and emission spectroscopy, steady state anisotropy, and time resolved
emission spectroscopy (TRES) as a function of temperature. Results were
interpreted using time dependent density functional theory calculations. Compared
to reference compounds of 3-HC substituted only in the 2 position, the compounds
show similar absorption and emission spectra, shifted 20-30 nm to higher
wavelengths due to extended conjugation. TRES shows the existence of ESIPT in the
thermodynamic equilibrium regime. This process is endothermic in all three
compounds. The different behavior compared to monosubstituted 3-HC is attributed
to the extended conjugation and to the electron donor acceptor character of the
substituents, which has a more pronounced effect when the electron acceptor is
located in position 2.
PMID- 28504971
TI - Robust tactile sensory responses in finger area of primate motor cortex relevant
to prosthetic control.
AB - OBJECTIVE: Challenges in improving the performance of dexterous upper-limb brain
machine interfaces (BMIs) have prompted renewed interest in quantifying the
amount and type of sensory information naturally encoded in the primary motor
cortex (M1). Previous single unit studies in monkeys showed M1 is responsive to
tactile stimulation, as well as passive and active movement of the limbs.
However, recent work in this area has focused primarily on proprioception. Here
we examined instead how tactile somatosensation of the hand and fingers is
represented in M1. APPROACH: We recorded multi- and single units and thresholded
neural activity from macaque M1 while gently brushing individual finger pads at 2
Hz. We also recorded broadband neural activity from electrocorticogram (ECoG)
grids placed on human motor cortex, while applying the same tactile stimulus.
MAIN RESULTS: Units displaying significant differences in firing rates between
individual fingers (p < 0.05) represented up to 76.7% of sorted multiunits
across four monkeys. After normalizing by the number of channels with significant
motor finger responses, the percentage of electrodes with significant tactile
responses was 74.9% +/- 24.7%. No somatotopic organization of finger preference
was obvious across cortex, but many units exhibited cosine-like tuning across
multiple digits. Sufficient sensory information was present in M1 to correctly
decode stimulus position from multiunit activity above chance levels in all
monkeys, and also from ECoG gamma power in two human subjects. SIGNIFICANCE:
These results provide some explanation for difficulties experienced by motor
decoders in clinical trials of cortically controlled prosthetic hands, as well as
the general problem of disentangling motor and sensory signals in primate motor
cortex during dextrous tasks. Additionally, examination of unit tuning during
tactile and proprioceptive inputs indicates cells are often tuned differently in
different contexts, reinforcing the need for continued refinement of BMI training
and decoding approaches to closed-loop BMI systems for dexterous grasping.
PMID- 28504973
TI - First-principles calculations of the magnetic and electronic structures of MnP
under pressure.
AB - Manganese monophosphide (MnP) shows complicated magnetic states varying with both
temperature and pressure. We calculate the magnetic and electronic structures of
MnP at different pressures using first-principles methods and obtain spiral
ground states whose propagation vector changes from the c-axis at low pressure to
the b-axis at high pressure. In between, we find a ferromagnetic state, as
observed in the experimental phase diagram. The propagation vector of the spiral
states is found to vary nonmonotonically with pressure, consistent with neutron
measurements. Our results indicate that the complicated magnetic phase diagram
originates from a delicate competition between neighboring exchange interactions
between the Mn-ions. At all pressures, the electronic structures indicate the
existence of quasi-one-dimensional charge carriers, which appear in the
ferromagnetic state and become gapped in the spiral state, and anisotropic three
dimensional charge carriers. We argue that this two-fluid behavior originates
from the special crystal structure of MnP and may be relevant for understanding
the pairing mechanism of the superconductivity at the border of the high pressure
spiral phase.
PMID- 28504970
TI - Osteoclast proton pump regulator Atp6v1c1 enhances breast cancer growth by
activating the mTORC1 pathway and bone metastasis by increasing V-ATPase
activity.
AB - It is known that V-ATPases (vacuolar H+-ATPase) are involved in breast cancer
growth and metastasis. Part of this action is similar to their role in
osteoclasts, where they're involved in extracellular acidification and matrix
destruction; however, the roles of their subunits in cancer cell proliferation,
signaling, and other pro-tumor actions are not well established. Analysis of TCGA
data shows that V-ATPase subunit Atp6v1c1 is overexpressed or amplified in 34% of
human breast cancer cases, with a 2-fold decrease in survival at 12 years.
Whereas other subunits, such as Atp6v1c2 and Atp6v0a3, are overexpressed or
genomically amplified less often, 6% each respectively, and have less impact on
survival. Experiments show that lentiviral-shRNA mediated ATP6v1c1 knockdown in
4T1 mouse mammary cancer cells significantly reduces orthotopic and intraosseous
tumor growth. ATP6v1c1 knockdown also significantly reduces tumor stimulated bone
resorption through osteoclastogenesis at the bone and metastasis in vivo, as well
as V-ATPase activity, proliferation, and mTORC1 activation in vitro. To
generalize the effects of ATP6v1c1 knockdown on proliferation and mTORC1
activation we used human cancer cell lines - MCF-7, MDA-MB-231, and MDA-MB-435s.
ATP6V1C1 knockdown reduced cell proliferation and impaired mTORC1 pathway
activation in cancer cells but not in the untransformed cell line C3H10T1/2. Our
study reveals that V-ATPase activity may be mediated through mTORC1 and that
ATP6v1c1 can be knocked down to block both V-ATPase and mTORC1 activity.
PMID- 28504974
TI - Diffusion and aggregation of oxygen vacancies in amorphous silica.
AB - Using density functional theory (DFT) calculations, we investigated oxygen
vacancy diffusion and aggregation in relation to dielectric breakdown in
amorphous silicon dioxide (a-SiO2). Our calculations indicate the existence of
favourable sites for the formation of vacancy dimers and trimers in the amorphous
network with maximum binding energies of approximately 0.13 eV and 0.18 eV,
respectively. However, an average energy barrier height for neutral vacancy
diffusion is found to be about 4.6 eV, rendering this process unfeasible. At
Fermi level positions above 6.4 eV with respect to the top of the valence band,
oxygen vacancies can trap up to two extra electrons. Average barriers for the
diffusion of negative and double negatively charged vacancies are found to be 2.7
eV and 2.0 eV, respectively. These barriers are higher than or comparable to
thermal ionization energies of extra electrons from oxygen vacancies into the
conduction band of a-SiO2. In addition, we discuss the competing pathways for
electron trapping in oxygen deficient a-SiO2 caused by the existence of intrinsic
electron traps and oxygen vacancies. These results provide new insights into the
role of oxygen vacancies in degradation and dielectric breakdown in amorphous
silicon oxides.
PMID- 28504975
TI - CE: Original Research: The Experiences of Pregnant Smokers and Their Providers.
AB - : : Background: The U.S. Department of Health and Human Services' initiative
Healthy People 2020 targets tobacco use, including smoking during pregnancy, as a
continuing major health concern in this country. Yet bringing the U.S. Public
Health Service's 2008 clinical practice guideline, Treating Tobacco Use and
Dependence, into routine prenatal care remains challenging. Our previous nurse
managed intervention study of rural pregnant women found no significant cessation
effect and significant discordance between self-reported smoker status and
urinary cotinine levels. PURPOSE: The overall purpose of this follow-up study was
to increase our understanding of the experiences of pregnant smokers and their
providers. No qualitative studies could be found that simultaneously explored the
experiences of both groups. DESIGN AND METHODS: This qualitative descriptive
study used focus group methodology. Nine focus groups were held in two counties
in upper New York State; six groups consisted of providers and three consisted of
pregnant women. Four semistructured questions guided the group discussions, which
were audiotaped and transcribed verbatim. Transcripts were read and coded
independently by six investigators. Themes were identified using constant
comparative analysis and were validated using the consensus process. RESULTS: The
total sample consisted of 66 participants: 45 providers and 21 pregnant women.
Most of the providers were white (93%) and female (93%). A majority worked as RNs
(71%); the sample included perinatal and neonatal nursery nurses, midwives, and
physicians. The pregnant women were exclusively white (reflecting the rural
demographic); the average age was 24 years. All the pregnant women had smoked at
the beginning of their pregnancies. Four common themes emerged in both the
provider and the pregnant women groups: barriers to quitting, mixed messages,
approaches and attitudes, and program modalities. These themes corroborate
previous findings that cigarette smoking is used for stress relief, especially
when pregnancy itself is a stressor, and that pregnant women may feel guilty but
don't want to be nagged or preached to. CONCLUSIONS: These results have
implications for how smoking cessation programs for pregnant women should be
designed. Health care providers need to be cognizant of their approaches and
attitudes when addressing the subject of smoking cessation. Specific educational
suggestions include "putting a face" to the issue of tobacco use during
pregnancy. More research is needed on how best to implement the 2008 clinical
practice guideline in specific populations.
PMID- 28504976
TI - CE: Antipsychotic Medications.
AB - : Antipsychotic medications are primarily used to manage various symptoms of
psychosis. In recent years, more adults-and teenagers-are taking at least one
type of psychotropic medication, the majority of which are prescribed by primary
care and family physicians. Because nurses are now caring for people of varying
ages, and with varying diagnoses, who are taking these types of medications, they
need to develop a working knowledge of the agents available and know when it's
appropriate to prescribe them for mental health disorders as well as for
disorders unrelated to mental health. This article is the first in a series on
commonly used psychotropic medications.
PMID- 28504977
TI - An Adolescent Male With Anorexia Nervosa Favorably Responded to Mirtazapine.
PMID- 28504978
TI - Beyond Googling: The Ethics of Using Patients' Electronic Footprints in
Psychiatric Practice.
AB - Electronic communications are an increasingly important part of people's lives,
and much information is accessible through such means. Anecdotal clinical reports
indicate that mental health professionals are beginning to use information from
their patients' electronic activities in treatment and that their data-gathering
practices have gone far beyond simply searching for patients online. Both
academic and private sector researchers are developing mental health applications
to collect patient information for clinical purposes. Professional societies and
commentators have provided minimal guidance, however, about best practices for
obtaining or using information from electronic communications or other online
activities. This article reviews the clinical and ethical issues regarding use of
patients' electronic activities, primarily focusing on situations in which
patients share information with clinicians voluntarily. We discuss the potential
uses of mental health patients' electronic footprints for therapeutic purposes,
and consider both the potential benefits and the drawbacks and risks. Whether
clinicians decide to use such information in treating any particular patient-and
if so, the nature and scope of its use-requires case-by-case analysis. But it is
reasonable to assume that clinicians, depending on their circumstances and goals,
will encounter circumstances in which patients' electronic activities will be
relevant to, and useful in, treatment.
PMID- 28504979
TI - Congenital Deafness Alters Sensory Weighting for Postural Control.
AB - OBJECTIVES: The aim of this study was to examine sensory reweighting for postural
control in congenitally deaf individuals. DESIGN: We studied 14 controls and 14
deaf age-matched individuals using a force platform and the modified clinical
test of sensory interaction and balance protocol. Both groups performed the
postural tasks without auditory cues (with hearing protectors for controls or
without hearing devices for the deaf). RESULTS: The results confirmed poorer
postural stability in the deaf. More importantly, the data suggest that
congenitally deaf individuals rely more on somatosensory information for postural
control than controls. CONCLUSIONS: This increased somatosensory reliance may
increase postural sway when it comes to more challenging postural conditions.
PMID- 28504980
TI - Hyperchloremia Is Associated With Acute Kidney Injury in Patients With
Subarachnoid Hemorrhage.
AB - OBJECTIVE: To assess the prevalence of acute kidney injury in patients with
subarachnoid hemorrhage patients. DESIGN: Retrospective analysis of all
subarachnoid hemorrhage admissions. SETTINGS: Neurocritical care unit. PATIENTS:
All patients with a diagnosis of subarachnoid hemorrhage between 2009 and 2014.
INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 1,267 patients included in
this cohort, 16.7% developed acute kidney injury, as defined by Kidney Disease
Improving Global Outcome criteria (changes in creatinine only). Compared to
patients without acute kidney injury, patients with acute kidney injury had a
higher prevalence of diabetes mellitus (21.2% vs 9.8%; p < 0.001) and
hypertension (70.3% vs 50.5%; p < 0.001) and presented with higher admission
creatinine concentrations (1.21 +/- 0.09 vs 0.81 +/- 0.01 mg/dL [mean +/- SD],
respectively; p < 0.001). Patients with acute kidney injury also had higher mean
serum chloride and sodium concentrations during their ICU stay (113.4 +/- 0.6 vs
107.1 +/- 0.2 mmol/L and 143.3 +/- 0.4 vs 138.8 +/- 0.1 mmol/L, respectively; p <
0.001 for both), but similar chloride exposure. The mortality rate was also
significantly higher in patients with acute kidney injury (28.3% vs 6.1% in the
non-acute kidney injury group [p < 0.001]). Logistic regression analysis revealed
that only male gender (odds ratio, 1.82; 95% CI, 1.28-2.59), hypertension (odds
ratio, 1.64; 95% CI, 1.11-2.43), diabetes mellitus (odds ratio, 1.88; 95% CI,
1.19-2.99), abnormal baseline creatinine (odds ratio, 2.48; 95% CI, 1.59-3.88),
and increase in mean serum chloride concentration (per 10 mmol/L; odds ratio,
7.39; 95% CI, 3.44-18.23), but not sodium, were associated with development of
acute kidney injury. Kidney recovery was noted in 78.8% of the cases. Recovery
reduced mortality compared to non-recovering subgroup (18.6% and 64.4%,
respectively; p < 0.001). CONCLUSIONS: Critically ill patients with subarachnoid
hemorrhage show a strong association between hyperchloremia and acute kidney
injury as well as acute kidney injury and mortality.
PMID- 28504981
TI - Perianal Epidermodysplasia Verruciformis Associated With Human Papillomavirus 5
After a Renal Transplant.
PMID- 28504982
TI - Characteristics, in-hospital management and outcome of late acute ST-elevation
myocardial infarction presenters.
AB - BACKGROUND: Patients with delayed presentation of acute myocardial infarction
with ST-segment elevation (STEMI) frequently have a poor prognosis but literature
about acute complications in intensive cardiac care unit (ICCU) and in-hospital
outcome are still limited. METHODS: All STEMI patients admitted to our
institution between June 2007 and December 2013 were divided into patients
presenting more than 12 h after symptom onset (lateSTEMI) and within 12 h
(STEMI). Baselines clinical features including details about treatment of choice
were collected. Major acute complications in ICCU and in-hospital mortality were
the main end-points. RESULTS: A total of 1372 patients were included, 147 (10.8%)
were lateSTEMI. In ICCU lateSTEMI patients compared with STEMI patients
experienced more frequently heart failure (75, 51.2% vs. 298, 24.3%; P < 0.001),
atrial fibrillation (26, 17.7% vs. 130, 10.6%; P = 0.011), complete
atrioventricular block (16, 10.9% vs. 63, 5.1%; P = 0.005), stroke (5, 3.4% vs.
5, 0.4%; P < 0.001), myocardial rupture (6, 4.1% vs. 3, 0.2%; P < 0.001), with
higher administration of noninvasive ventilation support therapy (13, 9.8% vs.
44, 3.6%; P = 0.001) and the intra-aortic balloon counter-pulsation use (14,
10.3% vs. 102, 8.3%; P = 0.038). Intrahospital mortality was significantly higher
in the lateSTEMI group (19, 13.4% vs. 69, 5.6%; P = 0.001). At the multiple
regression analysis age [odds ratio (OR) 2.2 (1.46-2.92.; P = 0.01)], diabetes
[OR 2.37 (1.38-4.07); P = 0.002] intra-aortic balloon counter-pulsation
implantation [OR 2.78 (1.30-5.9); P = 0.03] and late presentation more than 12 h
[2.52 (1.35-4.69); P = 0.001] resulted independently correlated with in-hospital
mortality while a successful percutaneous coronary intervention procedure was
protective [OR 0.15 (0.08-0.27); P = 0.003; all 95% confidence interval).
CONCLUSION: Late presenters STEMI patients present a worse risk profile and
prognosis compared with patients who arrive less than 12 h from onset of
symptoms. Because of the presence of serious complications such as heart rupture
or stroke a careful clinic and echocardiographic monitoring is strongly advisable
in these population.
PMID- 28504983
TI - Serum inhibitory factor 1, high-density lipoprotein and cardiovascular diseases.
AB - PURPOSE OF REVIEW: The atheroprotective properties of HDL are supported by
epidemiological and preclinical research. However, the results of interventional
trials paradoxically indicate that drugs increasing HDL-cholesterol (HDL-C) do
not reduce coronary artery disease (CAD) risk. Moreover, Mendelian randomization
studies have shown no effect of HDL-C-modifying variants on CAD outcome. Thus,
the protective effects of HDL particles are more governed by their functional
status than their cholesterol content. In this context, any successful clinical
exploitation of HDL will depend on the identification of HDL-related biomarkers,
better than HDL-C level, for assessing cardiovascular risk and monitoring
responses to treatment. RECENT FINDINGS: Recent studies have enlightened the role
of ecto-F1-ATPase as a cell surface receptor for apoA-I, the major apolipoprotein
of HDL, involved in the important metabolic and vascular atheroprotective
functions of HDL. In the light of these findings, the clinical relevance of ecto
F1-ATPase in humans has recently been supported by the identification of serum F1
ATPase inhibitor (IF1) as an independent determinant of HDL-C, CAD risk and
cardiovascular mortality in CAD patients. SUMMARY: Serum IF1 measurement might be
used as a novel HDL-related biomarker to better stratify risk in high-risk
populations or to determine pharmacotherapy.
PMID- 28504984
TI - Melding a High-Risk Patient for Continuous Flow Left Ventricular Assist Device
into a Low-Risk Patient.
AB - The model for end-stage liver disease (MELD) has been used as a predictor of
mortality after left ventricular assist device (LVAD) placement. However,
improvement or worsening of MELD and how those changes affect outcomes is
unknown. We performed a retrospective analysis of 244 patients implanted with a
continuous flow (CF) LVAD. Patients were dichotomized at admission into low- or
high-risk categories using a cutoff of MELD >= 19, and they were reclassified at
day of implant forming four groups: Group LL (low to low, remained low risk), LH
(low to high, worsened to high risk), HH (high to high, remained high risk), and
HL (high to low, improved to low risk). Patients who improved to a low risk
(group HL) had the same 1 year survival as those that remained low risk (group
LL; 80% vs. 77%; p = 0.6). However, patients who were initially classified as low
risk and worsened to a high risk (group LH) had a survival that was worse than
those that were consistently high risk (group HH; 55% vs. 10%; p = 0.01). Model
for end-stage liver disease reclassification after adjusting for commonly
attributed risk factors remained an independent predictor for mortality,
including patients classified as Interagency Registry for Mechanically Assisted
Circulatory Support (INTERMACS) 1 and 2. In conclusion, our MELD score
reclassification is an independent and powerful predictor of mortality in
patients undergoing LVAD implantation.
PMID- 28504985
TI - Current opinion in otolaryngology and head and neck surgery: frontal sinus
fractures.
AB - PURPOSE OF REVIEW: The purpose of this manuscript is to review the current
literature regarding the management of frontal sinus fractures and offer the
authors opinion on the current management of these traumatic injuries. We
evaluate recently proposed management algorithms as well as novel surgical
approaches reported within the last few years. RECENT FINDINGS: Patient selection
for sinus sparing treatment modalities is balanced between fracture severity,
involved structures, and reliable patient surveillance. Minimally invasive,
aesthetically favorable approaches grow in diversity for anterior table
fractures. For fractures of the posterior sinus wall and nasofrontal outflow
tract, the literature focuses on sinus sparing surgery, as well as better
defining the patients in which obliteration and/or cranialization is appropriate.
SUMMARY: Lack of large patient cohorts and follow-up limits generalizability of
frontal sinus fracture research, and the ability to develop national guidelines
of management. Evidence-based literature shows growing support for conservative
management and sinus preservation. Improvements in frontal sinus fracture
classification schemes, surgical technique, and patient selection direct this
treatment paradigm shift.
PMID- 28504986
TI - Cosmetic bone contouring.
AB - PURPOSE OF REVIEW: In recent years, cosmetic bone contouring surgery has become
increasingly popular, especially in East Asian countries. These procedures are
also being requested by patients in the United States at an increasing rate. The
purpose of this study is to provide an overview of what is involved with these
procedures and their potential complications. RECENT FINDINGS: In some cultures,
a wide jaw and a square face are aesthetically unpleasing, whereas an ovoid or
'melon seed face' is thought to be feminine, delicate and beautiful. Mandibular
angloplasty, mandibular lateral cortex excision, reduction malarplasty, as well
as genioplasty may be performed to alter the facial contour and bring about
dramatic results. SUMMARY: Whether a surgeon choses to incorporate these
procedures into practice or not, the craniofacial surgeons should be familiar
with the procedures as well as the potential complications.
PMID- 28504987
TI - Secondary reconstruction of maxillofacial trauma.
AB - PURPOSE OF REVIEW: Craniomaxillofacial trauma is one of the most complex clinical
conditions in contemporary maxillofacial surgery. Vital structures and possible
functional and esthetic sequelae are important considerations following this type
of trauma and intervention. Despite the best efforts of the primary surgery,
there are a group of patients that will have poor outcomes requiring secondary
reconstruction to restore form and function. The purpose of this study is to
review current concepts on secondary reconstruction to the maxillofacial complex.
RECENT FINDINGS: The evaluation of a posttraumatic patient for a secondary
reconstruction must include an assessment of the different subunits of the upper
face, middle face, and lower face. Virtual surgical planning and surgical guides
represent the most important innovations in secondary reconstruction over the
past few years. Intraoperative navigational surgery/computed-assisted navigation
is used in complex cases. Facial asymmetry can be corrected or significantly
improved by segmentation of the computerized tomography dataset and mirroring of
the unaffected side by means of virtual surgical planning. Navigational
surgery/computed-assisted navigation allows for a more precise surgical
correction when secondary reconstruction involves the replacement of extensive
anatomical areas. The use of technology can result in custom-made replacements
and prebent plates, which are more stable and resistant to fracture because of
metal fatigue. SUMMARY: Careful perioperative evaluation is the key to positive
outcomes of secondary reconstruction after trauma. The advent of technological
tools has played a capital role in helping the surgical team perform a given
treatment plan in a more precise and predictable manner.
PMID- 28504988
TI - The Labor Analgesia Requirements in Nulliparous Women Randomized to Epidural
Catheter Placement in a High or Low Intervertebral Space.
AB - BACKGROUND: We hypothesized that an epidural catheter placed in a lower vertebral
interspace will require less medication for labor analgesia. METHODS: Nulliparous
women requesting neuraxial labor analgesia were randomized to epidural catheter
placement at the ultrasound-confirmed L1-2 or L4-5 interspace. Patient-controlled
epidural analgesia and breakthrough manual epidural boluses of 10 mL of 0.125%
bupivacaine with 50 ug of fentanyl or 8 mL of 2% lidocaine were utilized.
Abdominal and perineal pain scores were assessed at 30 and 60 minutes after
standardized initiation of epidural analgesia. Pain scores during pushing were
assessed after delivery. The primary outcome was the proportion of patients
requiring manual boluses and was compared using a chi test. Secondarily, we
analyzed the number of boluses given in early (up to 4 hours before delivery)
versus late labor using chi tests and the pain scores using Mann-Whitney U tests,
with adjustment of P values for multiple testing. RESULTS: We analyzed 148
patients. Overall, the percentage of patients in the low versus high groups who
required manual boluses was 46% vs 51% (P = 1.0). For the 56 patients in each
group who delivered vaginally, 22 (52%) vs 20 (48%) manual boluses were given to
the low epidural group in early versus late labor, compared to 9 (20%) vs 36
(80%) in the high epidural group (P = .014). There was no statistical difference
in patient-controlled epidural analgesia requirements or patient satisfaction.
Comparing the low versus high groups, the median (interquartile range) pain
scores were: 3 (1, 6) vs 0 (0, 2) (P = .013) at 30 minutes and 1 (1, 3) vs 0 (0,
1) (P = .013) at 60 minutes for abdominal pain; 0 (0, 2) vs 1 (1, 3) (P = .36)
and 0 (0, 1) vs 1 (1, 3) (P = .014) at these same time points for perineal pain;
and 1 (0, 5) vs 0 (0, 3) (P = .9) for abdominal and 2 (0, 5) vs 4 (1, 8) (P =
.025) for perineal pain during pushing. The percentage of patients who underwent
instrumental delivery was 15% vs 5% (P = .06) for the low versus high group.
CONCLUSIONS: An L4-5 epidural catheter initially provides less relief of
abdominal pain but more relief of perineal labor pain. Patients with an L4-5
catheter require more manual boluses during early labor but less during late
labor. The possible association of low epidural catheters with instrumental
delivery merits further investigation.
PMID- 28504989
TI - Structural Behavior of the Endothelial Glycocalyx Is Associated With
Pathophysiologic Status in Septic Mice: An Integrated Approach to Analyzing the
Behavior and Function of the Glycocalyx Using Both Electron and Fluorescence
Intravital Microscopy.
AB - BACKGROUND: The endothelial surface layer (ESL) regulates vascular permeability
to maintain fluid homeostasis. The glycocalyx (GCX), which has a complex and
fragile ultrastructure, is an important component of the ESL. Abnormalities of
the GCX have been hypothesized to trigger pathological hyperpermeability. Here,
we report an integrated in vivo analysis of the morphological and functional
properties of the GCX in a vital organ. METHODS: We examined the behavior of the
ESL and GCX, using both electron microscopy (EM) and intravital microscopy (IVM).
We also compared morphological changes in the ESL of mouse skin in a glycosidase
treated and control group. Combined approaches were also used to examine both
morphology and function in a lipopolysaccharide-induced septic model and the
pathophysiological features of leukocyte-endothelial interactions and in vivo
vascular permeability. RESULTS: Using IVM, we identified an illuminated part of
the ESL as the GCX and confirmed our observation using morphological and
biochemical means. In septic mice, we found that the GCX was thinner than in
nonseptic controls in both an EM image analysis (0.98 +/- 2.08 nm vs 70.68 +/-
36.36 nm, P< .001) and an IVM image analysis (0.36 +/- 0.15 MUm vs 1.07 +/- 0.39
MUm, P< .001). Under septic conditions, syndecan-1, a representative core protein
of the GCX, was released into the blood serum at a higher rate in septic animals
(7.33 +/- 3.46 ng/mL) when compared with controls (below the limit of detection,
P< .001). Significant increases in leukocyte-endothelial interactions, defined as
the numbers of rolling or firm-sticking leukocytes, and molecular
hyperpermeability to the interstitium were also observed after GCX shedding in
vivo. CONCLUSIONS: Using IVM, we visualized an illuminated part of the ESL layer
that was subsequently confirmed as the GCX using EM. Severe sepsis induced
morphological degradation of the GCX, accompanied by shedding of the syndecan-1
core protein and an increase in leukocyte-endothelial interactions affecting the
vascular permeability. Our in vivo model describes a new approach to deciphering
the relationship between structural and functional behaviors of the GCX.
PMID- 28504990
TI - A Structured Transfer of Care Process Reduces Perioperative Complications in
Cardiac Surgery Patients.
AB - INTRODUCTION: Serious complications are common during the intensive care of
postoperative cardiac surgery patients. Some of these complications may be
influenced by communication during the process of handover of care from the
operating room to the intensive care unit (ICU) team. A structured transfer of
care process may reduce the rate of communication errors and perioperative
complications. METHODS: We hypothesized that a collaborative, comprehensive,
structured handover of care from the intraoperative team to the ICU team would
reduce a specific set of postoperative complications. We tested this hypothesis
by developing and introducing a comprehensive multidisciplinary transfer of care
process. We measured patient outcomes before and after the intervention using a
linkage between 2 care databases: an Anesthesia Information Management System and
a critical care complication registry database. RESULTS: There were 1127 total
postoperative cardiac surgery admissions during the study period, 550 before and
577 after the intervention. There was no statistical difference between overall
complications before and after the intervention (P = .154). However, there was a
statistically significant reduction in preventable complications after the
intervention (P = .023). DISCUSSION: The main finding of this investigation is
that the introduction of a collaborative, comprehensive transfer of care process
from the operating room to the ICU was associated with patients suffering fewer
preventable complications.
PMID- 28504991
TI - Tablet e-Logbooks: Four Thousand Clinical Cases and Complications e-Logged by 14
Nondoctor Anesthesia Providers in Nepal.
AB - BACKGROUND: To meet the need for essential surgery across rural Nepal, anesthesia
at district level is delivered by nondoctor anesthetists. They require support to
maintain confidence and competence, and upgraded professional registration to
secure their status. To meet these needs, a distance-blended learning course was
pioneered and delivered. A core course requirement was to log all clinical cases;
these were logged on a new e-logbook. METHODS: Fourteen nondoctor anesthesia
providers working in 12 different districts across Nepal were enrolled in the 1
year course. The course is based on self-completion on a tablet loaded with new
learning modules, a resource library, and a case logbook. Continuous educational
mentoring was provided by anesthesiologists by phone and email. The logbook
included preanesthesia assessment and interventions, American Society of
Anesthesiologists (ASA) grading, types of cases and anesthesia given, monitors
used, complications, outcomes and free text remarks. Cases were uploaded monthly
to a database, and mentors reviewed all logbook entries. RESULTS: The 14
nondoctor anesthesia providers were widely distributed across the country in
district, zonal, community, and mission hospitals, and had different levels of
clinical experience and caseloads. Logbooks and uploads were regularly completed
without difficulty; 1% cases were entered incompletely with no case details
provided. A total of 4143 cases were recorded. Annual caseload per nondoctor
anesthesia provider ranged from 50 to 788, the majority of which were under
spinal anesthesia; 34% of the total cases were cesarean deliveries, of which 99%
received spinal anesthesia. Fifty gastrointestinal laparotomies (1% total) were
recorded. Ninety-one percent of cases were ASA I, 0.8% ASA III/IV. Pulse oximetry
was used in 98% of cases. Complications were recorded in 6% of cases; the most
common were circulation problems (69%) including hypotension and occasional
bradycardia after spinal anesthesia. Airway complications were usually under
ketamine anesthesia requiring basic airway maneuvers; 4 difficult intubations
were recorded under general anesthesia. Anesthesia outcomes were good with
overall mortality of 0.1% (total 4 cases). Causes of death included severe
preeclampsia, sepsis postlaparotomy, and patients with multiorgan failure for
minor procedure. CONCLUSIONS: The tablet-based electronic anesthesia logbook was
successfully used to record cases, complications, and outcomes across rural
Nepal. The nondoctor anesthesia providers had trust and confidence in recording
outcomes. It remains to be tested whether an e-logbook would be routinely
completed outside of a specific training course. Such a logbook could be
incorporated into all continuous professional development programs for rural
nondoctor anesthetists.
PMID- 28504992
TI - Trends in Perioperative Practice and Resource Utilization in Patients With
Obstructive Sleep Apnea Undergoing Joint Arthroplasty.
AB - BACKGROUND: Emerging evidence associating obstructive sleep apnea (OSA) with
adverse perioperative outcomes has recently heightened the level of awareness
among perioperative physicians. In particular, estimates projecting the high
prevalence of this condition in the surgical population highlight the necessity
of the development and adherence to "best clinical practices." In this context, a
number of expert panels have generated recommendations in an effort to provide
guidance for perioperative decision-making. However, given the paucity of
insights into the status of the implementation of recommended practices on a
national level, we sought to investigate current utilization, trends, and the
penetration of OSA care-related interventions in the perioperative management of
patients undergoing lower joint arthroplasties. METHODS: In this population-based
analysis, we identified 1,107,438 (Premier Perspective database; 2006-2013) cases
of total hip and knee arthroplasties and investigated utilization and temporal
trends in the perioperative use of regional anesthetic techniques, blood oxygen
saturation monitoring (oximetry), supplemental oxygen administration, positive
airway pressure therapy, advanced monitoring environments, and opioid
prescription among patients with and without OSA. RESULTS: The utilization of
regional anesthetic techniques did not differ by OSA status and overall <25% and
15% received neuraxial anesthesia and peripheral nerve blocks, respectively.
Trend analysis showed a significant increase in peripheral nerve block use by
>50% and a concurrent decrease in opioid prescription. Interestingly, while the
absolute number of patients with OSA receiving perioperative oximetry,
supplemental oxygen, and positive airway pressure therapy significantly increased
over time, the proportional use significantly decreased by approximately 28%,
36%, and 14%, respectively. A shift from utilization of intensive care to
telemetry and stepdown units was seen. CONCLUSIONS: On a population-based level,
the implementation of OSA-targeted interventions seems to be limited with some of
the current trends virtually in contrast to practice guidelines. Reasons for
these findings need to be further elucidated, but observations of a dramatic
increase in absolute utilization with a proportional decrease may suggest
possible resource constraints as a contributor.
PMID- 28504993
TI - Red Blood Cell Transfusion and Surgical Site Infection After Colon Resection
Surgery: A Cohort Study.
AB - BACKGROUND: Surgical site infections (SSIs) after colon surgery remain a critical
safety issue. Patients with an SSI have an increased risk of death, prolonged
hospitalization, and increased costs of care. Red blood cell (RBC) transfusion is
given during the perioperative period to increase blood oxygen delivery, but it
is associated with complications, including infection. We hypothesized that RBC
transfusion would be associated with increased SSI risk in patients undergoing
colon resection surgery. METHODS: A retrospective cohort study was performed
using the 2014 National Surgical Quality Improvement Program participant use
file. Patients who had colon resection surgery were identified using current
procedural terminology codes. The association between perioperative RBC
transfusion and superficial and deep incisional SSIs, organ space SSIs, and
postoperative septic shock was modeled using logistic regression with propensity
score analysis. RESULTS: Of 23,388 patients who had colon resection surgery, 1845
(7.9%) received perioperative RBC transfusion. After controlling for confounders
with propensity score analysis and inverse probability of treatment weighting,
RBC transfusion had no apparent association with superficial incisional SSI (odds
ratio [OR], 1.18; 99% confidence interval [CI], 0.48-2.88) or deep incisional SSI
(OR, 1.47; 99% CI, 0.23-9.43). However, RBC transfusion appeared to be associated
with increased risk of organ space SSI (OR, 2.93; 99% CI, 1.43-6.01) and septic
shock (OR, 9.23; 99% CI, 3.53-24.09). CONCLUSIONS: RBC transfusion has no
apparent association with increased risk for incisional SSIs, but may be
associated with increased risk for organ space SSI and septic shock after colon
resection surgery.
PMID- 28504994
TI - Preoperative Low-Dose Aspirin Exposure and Outcomes After Emergency Neurosurgery
for Traumatic Intracranial Hemorrhage in Elderly Patients.
AB - BACKGROUND: Antiplatelet medications are usually discontinued before elective
neurosurgery, but this is not an option for emergent neurosurgery. We performed a
retrospective cohort study to examine whether preoperative aspirin use was
associated with worse outcomes after emergency neurosurgery in elderly patients.
METHODS: We analyzed all cases of emergency neurosurgical procedures for
traumatic intracranial hemorrhage from 2008 to 2012 at a level 1 trauma center.
Demographics, comorbidities, and outcomes were compared for patients >=65 years
by preoperative aspirin exposure. Exclusion criteria were: (1) polytrauma, (2)
concomitant use of other preoperative anticoagulants or antiplatelet agents, (3)
surgical indication other than subdural, extradural, or intraparenchymal
hemorrhage, and (4) repeat neurosurgical procedures within a single admission.
Estimated intraoperative blood loss, postprocedural intracranial bleeding
requiring reoperation, death in hospital, intensive care unit, and hospital
lengths of stay and perioperative blood product transfusion from 48 hours before
48 hours after surgery were the study outcomes. We also examined whether platelet
transfusion had an impact on outcomes for patients on aspirin. RESULTS: The
cohort included 171 patients. Patients receiving preoperative aspirin (n = 87,
95% taking 81 mg/day) were the same age as patients not receiving aspirin (n =
84; 78.3 +/- 7.8 vs 75.9 +/- 7.9 years, P > .05), had slightly higher admission
Glasgow Coma Scale scores (12.8 +/- 3.4 vs 11.4 +/- 4, P = .02) and tended to
have more coronary artery disease (P< .05). Adjusted for Glasgow Coma Scale and
coronary artery disease, patients receiving preoperative aspirin had a higher
odds of perioperative platelet transfusion (adjusted odds ratio 9.89, 95%
confidence interval, 4.24-26.25). There were no other differences in outcomes
between the 2 groups. Preoperative or intraoperative platelet transfusion was not
associated with better outcomes among aspirin patients. CONCLUSIONS: In patients
age >=65 years undergoing emergency neurosurgery for traumatic intracranial
hemorrhage, preoperative low-dose aspirin treatment was not associated with
increased perioperative bleeding, hospital lengths of stay, or in-hospital
mortality.
PMID- 28504995
TI - Remote Ischemic Preconditioning Decreases Oxidative Lung Damage After Pulmonary
Lobectomy: A Single-Center Randomized, Double-Blind, Controlled Trial.
AB - BACKGROUND: During lobectomy in patients with lung cancer, the operated lung is
often collapsed and hypoperfused. Ischemia/reperfusion injury may then occur when
the lung is re-expanded. We hypothesized that remote ischemic preconditioning
(RIPC) would decrease oxidative lung damage and improve gas exchange in the
postoperative period. METHODS: We conducted a single-center, randomized, double
blind trial in patients with nonsmall cell lung cancer undergoing elective lung
lobectomy. Fifty-three patients were randomized to receive limb RIPC immediately
after anesthesia induction (3 cycles: 5 minutes ischemia/5 minutes reperfusion
induced by an ischemia cuff applied on the thigh) and/or control therapy without
RIPC. Oxidative stress markers were measured in exhaled breath condensate (EBC)
and arterial blood immediately after anesthesia induction and before RIPC and
surgery (T0, baseline); during operated lung collapse, immediately before
resuming two-lung ventilation (TLV) (T1); immediately after resuming TLV (T2);
and 120 minutes after resuming TLV (T3). The primary outcome was 8-isoprostane
levels in EBC at T1, T2, and T3. Secondary outcomes included the following:
NO2+NO3, H2O2 levels, and pH in EBC and in blood (8-isoprostane, NO2+NO3) and
pulmonary gas exchange variables (PaO2/FiO2, A-aDO2, a/A ratio, and respiratory
index). RESULTS: Patients subjected to RIPC had lower EBC 8-isoprostane levels
when compared with controls at T1, T2, and T3 (differences between means and 95%
confidence intervals): -15.3 (5.8-24.8), P = .002; -20.0 (5.5-34.5), P = .008;
and -10.4 (2.5-18.3), P = .011, respectively. In the RIPC group, EBC NO2+NO3 and
H2O2 levels were also lower than in controls at T2 and T1-T3, respectively (all P
< .05). Blood levels of 8-isoprostane and NO2+NO3 were lower in the RIPC group at
T2 (P < .05). The RIPC group had better PaO2/FiO2 compared with controls at 2
hours, 8 hours, and 24 hours after lobectomy in 95% confidence intervals for
differences between means: 78 (10-146), 66 (14-118), and 58 (12-104),
respectively. CONCLUSIONS: Limb RIPC decreased EBC 8-isoprostane levels and other
oxidative lung injury markers during lung lobectomy. RIPC also improved
postoperative gas exchange as measured by PaO2/FiO2 ratio.
PMID- 28504996
TI - Stroke Volume Variation and Pulse Pressure Variation Are Not Useful for
Predicting Fluid Responsiveness in Thoracic Surgery.
AB - BACKGROUND: Stroke volume variation (SVV) and pulse pressure variation (PPV) are
used as indicators of fluid responsiveness, but little is known about the
usefulness of these dynamic preload indicators in thoracic surgery, which
involves an open thoracic cavity and 1-lung ventilation (OLV). Therefore, we
investigated whether SVV and PPV could predict fluid responsiveness, and whether
the thresholds of these parameters should be adjusted for thoracic surgery.
METHODS: This was a prospective, controlled study conducted in a tertiary care
center. Eighty patients scheduled for an elective lobectomy requiring OLV were
included (n = 40, video-assisted thoracoscopic surgery (VATS); n = 40, open
thoracotomy). Twenty minutes after opening the thoracic cavity, 7 mL/kg
hydroxyethyl starch was administered for 30 minutes. Various hemodynamic
parameters were measured before and after fluid challenge. RESULTS: Among the 80
patients enrolled in this study, 37% were fluid responders (increase in stroke
volume index >=10%). SVV before fluid challenge was not different between
nonresponders and responders (mean +/- SD: 7.1 +/- 2.7% vs 7.4 +/- 2.6%, P =
.68). This finding was true regardless of whether the surgery involved open
thoracotomy or VATS. PPV before fluid challenge showed the difference between
nonresponders and responders (mean +/- SD: 6.9 +/- 3.0% vs 8.4 +/- 3.2%; P =
.045); however, the sensitivity and specificity of the threshold value (PPV = 7%)
were low (58% and 62%, respectively) and the area under the receiver operating
characteristics curve was only 0.63 (95% confidence interval, 0.52-0.74; P =
.041). CONCLUSIONS: Dynamic preload indicators are not useful for predicting
fluid responsiveness in VATS or open thoracic surgery.
PMID- 28504998
TI - Introduction.
PMID- 28504997
TI - Lung Rest During Extracorporeal Membrane Oxygenation for Neonatal Respiratory
Failure-Practice Variations and Outcomes.
AB - OBJECTIVE: Describe practice variations in ventilator strategies used for lung
rest during extracorporeal membrane oxygenation for respiratory failure in
neonates, and assess the potential impact of various lung rest strategies on the
duration of extracorporeal membrane oxygenation and the duration of mechanical
ventilation after decannulation. DATA SOURCES: Retrospective cohort analysis from
the Extracorporeal Life Support Organization registry database during the years
2008-2013. STUDY SELECTION: All extracorporeal membrane oxygenation runs for
infants less than or equal to 30 days of life for pulmonary reasons were
included. DATA EXTRACTION: Ventilator type and ventilator settings used for lung
rest at 24 hours after extracorporeal membrane oxygenation initiation were
obtained. DATA SYNTHESIS: A total of 3,040 cases met inclusion criteria.
Conventional mechanical ventilation was used for lung rest in 88% of cases and
high frequency ventilation was used in 12%. In the conventional mechanical
ventilation group, 32% used positive end-expiratory pressure strategy of 4-6 cm
H2O (low), 22% used 7-9 cm H2O (mid), and 43% used 10-12 cm H2O (high). High
frequency ventilation was associated with an increased mean (SEM) hours of
extracorporeal membrane oxygenation (150.2 [0.05] vs 125 [0.02]; p < 0.001) and
an increased mean (SEM) hours of mechanical ventilation after decannulation (135
[0.09] vs 100.2 [0.03]; p = 0.002), compared with conventional mechanical
ventilation among survivors. Within the conventional mechanical ventilation
group, use of higher positive end-expiratory pressure was associated with a
decreased mean (SEM) hours of extracorporeal membrane oxygenation (high vs low:
136 [1.06] vs 156 [1.06], p = 0.001; mid vs low: 141 [1.06] vs 156 [1.06]; p =
0.04) but increased duration of mechanical ventilation after decannulation in the
high positive end-expiratory pressure group compared with low positive end
expiratory pressure (p = 0.04) among survivors. CONCLUSIONS: Wide practice
variation exists with regard to ventilator settings used for lung rest during
neonatal respiratory extracorporeal membrane oxygenation. Use of high frequency
ventilation when compared with conventional mechanical ventilation and use of low
positive end-expiratory pressure strategy when compared with mid positive end
expiratory pressure and high positive end-expiratory pressure strategy is
associated with longer duration of extracorporeal membrane oxygenation. Further
research to provide evidence to drive optimization of pulmonary management during
neonatal respiratory extracorporeal membrane oxygenation is warranted.
PMID- 28504999
TI - Tumor Microenvironment and Checkpoint Molecules in Primary Cutaneous Diffuse
Large B-Cell Lymphoma-New Therapeutic Targets.
AB - Programmed death ligand 1 (PD-L1) is expressed by 20% to 57% of systemic diffuse
large B cell lymphomas (DLBCLs). PD-L1 expression in primary cutaneous DLBCL
(pcDLBCL) has not been studied so far. Sixteen paraffin-embedded tissue samples
of pcDLBCL (13 leg type [LT], 3 others [OT]) were investigated for PD-1, PD-L1,
and CD33 expression and the cellular composition of the tumor microenvironment,
focusing on myeloid-derived suppressor cells (MDSCs) and tumor-associated
macrophages. Membrane-bound PD-L1 expression by the tumor cells was observed in
all samples, albeit to a variable extent (19.9%). As expected, most DLBCL-LT (10
cases) were classified as activated B cell like type, with a higher PD-L1 score
(21.9%) compared with that of the germinal center B cell like type (7.7%). The
surrounding infiltrate consisted predominately of CD163(+) M2 rather than CD68(+)
macrophages (CD68:CD163=1:4 to 6). Moreover, a considerable proportion of CD33(+)
MDSCs with PD-L1 coexpression was admixed. Tumor cells expressed CD33 to variable
degrees (2% to 60%). The number of MDSCs or M2 macrophages did not correlate with
pcDLBCL subtypes LT or OT. T cells were only a minor component of the tumor
microenvironment. We propose that PD-L1(+) tumor cells and PD-L1(+) MDSCs shield
the tumor against PD-1(+) tumor-infiltrating lymphocytes, consequently leading to
inhibition and diminution of tumor-infiltrating lymphocytes. Moreover, we found a
polarization to M2 macrophages, which may contribute to the poor prognosis of
DLBCL patients. Thus, targeting of tumor cells and MDSCs using anti-PD-1/anti-PD
L1 or anti-CD33 antibodies might be a worthwhile new approach to treat this
aggressive form of cutaneous B-cell lymphoma.
PMID- 28505001
TI - The Impact of P16 Immunostaining in Reducing Anal Squamous Intraepithelial
Lesions Indication for Treatment.
PMID- 28505000
TI - H3F3A (Histone 3.3) G34W Immunohistochemistry: A Reliable Marker Defining Benign
and Malignant Giant Cell Tumor of Bone.
AB - Giant cell tumor of bone (GCTB) is a locally aggressive subarticular tumor.
Having recently reported that H3.3 G34W mutations are characteristic of this
tumor type, we have now investigated the sensitivity and specificity of the anti
histone H3.3 G34W rabbit monoclonal antibody in a wide variety of tumors
including histologic mimics of GCTB to assess its value as a diagnostic marker.
We also determined the incidence of H3.3 G34 mutations in primary malignant bone
tumors as assessed by genotype and H3.3 G34W immunostaining. A total of 3163
tumors were tested. Totally, 213/235 GCTB (90.6%) showed nuclear H3.3 p.G34W
immunoreactivity. This was not the case for the rare variants, p.G34L, M, and V,
which occurred most commonly in the small bones of the hands, patella, and the
axial skeleton. If these sites were excluded from the analysis, H3.3 G34W
expression was found in 97.8% of GCTB. Malignant bone tumors initially classified
as osteosarcomas were the only other lesions (n=11) that showed G34W expression.
Notably an additional 2 previously reported osteosarcomas with a p.G34R mutation
were not immunoreactive for the antibody. A total of 11/13 of these malignant
H3.3-mutant tumors exhibited an osteoclast-rich component: when imaging was
available all but one presented at a subarticular site. We propose that
subarticular primary malignant bone sarcoma with H3.3 mutations represent true
malignant GCTB, even in the absence of a benign GCTB component.
PMID- 28505002
TI - Immunohistochemical Classification of Ampullary Carcinomas: Critical Reappraisal
Fails to Confirm Prognostic Relevance for Recently Proposed Panels, and
Highlights MUC5AC as a Strong Prognosticator.
AB - Recently, immunohistochemistry-based classifications of ampullary carcinomas have
been proposed (Ang and colleagues [PMID: 24832159]; Chang and colleagues [PMID:
23439753]). In this study, the prognostic value of Ang/Chang panel markers (CK20,
MUC1, MUC2, CDX2) as well as other markers (CK7, MUC5AC, and MUC6) were tested on
full-faced sections of 136 ampullary carcinoma resections with substantial (>5
mm) invasion. Immunohistochemistry was correlated with both histologic
classification (intestinal [INT], pancreatobiliary [PB], or nontubular based on
>=3/5 observer agreement) and clinical outcome. No prognostic correlation was
found with MUC1, CDX2, MUC2 or CK20 despite testing with different quantitative
cutoffs. CK7 and CK20 were nonspecific. Ang classification had reasonable
correlation with histologic subclassification of tubular cases as INT versus PB
with high specificity but low sensitivity and ambiguous category was large (29%)
and included also some classical cases. Prognostically, Ang classification
approached but did not reach statistical significance, even when their large
"ambiguous" group was eliminated and only tubular cases were analyzed (Ang-INT
vs. Ang-PB; P=0.08). The Chang panel, in which the definition of the INT
subcategory is not clearly defined, only marginally reached prognostic
significance when tested as MUC1+/CDX2- versus MUC1-/CDX2+ and only by Wilcoxon
test (P=0.0485) but 31% of the cases were "unclassifiable." The only individual
marker that was found to have direct and strong correlation with the clinical
outcome was MUC5AC (not used in the Ang or Chang panels), with statistically
significant survival differences found with various cutoffs tested (for 20%
cutoff, 5-y survival, 68% vs. 31%; P=0.0002). In addition, MUC5AC significantly
stratified the histologically PB and INT cases (P=0.01 and 0.03, respectively),
as well as Ang's ambiguous and Chang's unclassified cases (P=0.006 and 0.007,
respectively). In conclusion, the widely used putative lineage markers,
MUC1/MUC2/CK7/CK20/CDX2, do not seem to have direct/significant prognostic
correlation either individually or in combination of Ang and Chang panels. Ang
panel is helpful as an adjunct in determining the cell lineage with a few
caveats. MUC5AC proves to be a significant independent prognosticator and should
be incorporated into evaluation of ampullary carcinomas.
PMID- 28505003
TI - The Adequacy of Core Biopsy in the Assessment of Smooth Muscle Neoplasms of Soft
Tissues: Implications for Treatment and Prognosis.
AB - The grading of soft tissue sarcomas is one of the most important prognostic
factors and determines patient management. Although grading of most adult-type
soft tissue sarcomas on biopsies correlates highly with the final grading on the
excision specimen, it appears less reliable for tumors of smooth muscle. We
assessed the pathologic findings for smooth muscle neoplasms diagnosed by core
biopsy at our tertiary sarcoma center, and compared them with those in the
subsequent excision specimens. A total of 100 patients with leiomyosarcoma first
diagnosed on core biopsy and with a subsequent excision were identified and the
accuracy of the biopsy grade determined by comparison with the excision grade.
Differences in other salient histologic parameters were also noted. A grade
difference between biopsy and excision specimens of leiomyosarcomas was found in
68% of cases, with all these cases showing an increase in grade from biopsy to
excision specimen. Of the 3 parameters used for grading using the French
Federation of Cancer Centers Sarcoma Group Grading System (FNCLCC), necrosis was
the score that most commonly differed between biopsy and excision specimen (55%),
closely followed by the mitotic count (51%). The grading of soft tissue smooth
muscle tumor biopsies has a lower accuracy compared with other adult soft tissue
sarcomas and should therefore be taken with caution, particularly as this may be
an underrepresentation of the true tumor grade.
PMID- 28505005
TI - Gastric Cancer With Primitive Enterocyte Phenotype: An Aggressive Subgroup of
Intestinal-type Adenocarcinoma.
AB - A primitive cell-like gene expression signature is associated with aggressive
phenotypes of various cancers. We assessed the expression of phenotypic markers
characterizing primitive cells and its correlation with clinicopathologic and
molecular characteristics in gastric cancer. Immunohistochemical analysis of a
panel of primitive phenotypic markers, including embryonic stem cell markers
(OCT4, NANOG, SALL4, CLDN6, and LIN28) and known oncofetal proteins (AFP and
GPC3), was performed using tissue microarray on 386 gastric cancers. On the basis
of the expression profiles, the 386 tumors were clustered into 3 groups: group 1
(primitive phenotype, n=93): AFP, CLDN6, GPC3, or diffuse SALL4 positive; group 2
(SALL4-focal, n=56): only focal SALL4 positive; and group 3 (negative, n=237):
all markers negative. Groups 1 and 2 predominantly consisted of intestinal-type
adenocarcinoma, including 13 fetal gut-like adenocarcinomas exclusively in group
1. Group 1 was significantly associated with higher T-stage, presence of vascular
invasion and nodal metastasis when compared with groups 2 and 3. Group 1 was
associated with patients' poor prognosis and was an independent risk factor for
disease-free survival. Group 1 showed frequent TP53 overexpression and little
association with Epstein-Barr virus or mismatch repair deficiency. Further
analysis of the Cancer Genome Atlas data set validated our observations and
revealed that tumors with primitive phenotypes were mostly classified as
"chromosomal instability" in the Cancer Genome Atlas' molecular classification.
We identified gastric cancer with primitive enterocyte phenotypes as an
aggressive subgroup of intestinal-type/chromosomal instability gastric cancer.
Therapeutic strategies targeting primitive markers, such as GPC3, CLDN6, and
SALL4, are highly promising.
PMID- 28505004
TI - A Subset of Malignant Mesotheliomas in Young Adults Are Associated With Recurrent
EWSR1/FUS-ATF1 Fusions.
AB - Malignant mesothelioma (MM) is a rare, aggressive tumor often associated with
asbestos exposure and characterized by complex genetic abnormalities, including
deletions of chromosome 22. A gene fusion involving EWSR1 and YY1 gene on 14q32
has been reported in 2 patients over the age of 60 with peritoneal MM. However,
the incidence of EWSR1 rearrangements in MM and the spectrum of its fusion
partners remain unknown. We recently encountered 2 MM cases with EWSR1-ATF1
fusions and sought to investigate the prevalence and clinicopathologic features
associated with this abnormality. As both index cases occurred as intra-abdominal
tumors in young adults, we searched our files for pleural and peritoneal MM
occurring in adults younger than age of 40. All cases were tested by fluorescence
in situ hybridization using custom bacterial artificial chromosomes probes for
EWSR1, FUS, and ATF1 genes. When available, immunohistochemistry for BAP1 was
performed. A total of 25 MM from patients aged 40 or less were screened, either
from peritoneum (n=13) or pleura (n=12), with a median age of 31 (range: 7 to 40
y). Two additional ATF1-rearranged tumors were identified at pleural and
peritoneal sites with EWSR1 and FUS as fusion partners, respectively, for a total
of 4 cases (16%, 4/25). The fusion-positive cases displayed classic epithelioid
morphology, immunoreactivity for cytokeratins and WT1, and negativity for S100.
BAP1 expression was retained in the 3 fusion-positive cases with available
material, and in 80% (12/15) of the fusion-negative cases. Our results expand the
spectrum of tumor types harboring EWSR1/FUS-ATF1 gene fusions to include a
subgroup of conventional epithelioid MM. Other features of this unique MM subset
include young age at presentation, lack of asbestos exposure and retained BAP1
expression.
PMID- 28505006
TI - Myopericytomatosis: Clinicopathologic Analysis of 11 Cases With Molecular
Identification of Recurrent PDGFRB Alterations in Myopericytomatosis and
Myopericytoma.
AB - Myopericytoma is a benign tumor of concentrically distributed perivascular myoid
cells. Its molecular basis and relationship with myofibroma/myofibromatosis and
other pericytic tumors are not fully understood. In our consultation/surgical
files of over 1000 myopericytic lesions, we identified 11 cases with diffuse
dermal/subcutaneous involvement by microscopic myopericytomatous nodules, a
phenomenon we have termed myopericytomatosis. Myopericytomatosis affected mostly
adults (female:male=8:3; median age, 37 y; range, 9 to 63 y) in the lower
extremities (foot/ankle, 5; calf, 3; knee, 1; thigh, 1; neck, 1) over months to
25 years, ranging from 1.5 to 11.0 (median, 6.0) cm in size. Histologically,
myopericytomatosis displayed diffuse infiltration by innumerable discrete
myopericytoma/myofibroma-like nodules of bland spindled-to-ovoid cells (smooth
muscle actin positive), in a mainly perivascular distribution. No mitoses,
atypia, or necrosis was noted. All patients were treated by surgical excision (1
patient also received adjuvant radiation), with margins focally positive in 5 of
6 known cases. Of the 6 cases with follow-up of 0.2 to 13.7 (median, 3.4) years,
1 recurred locally twice, while 5 cases showed no recurrence. Targeted next
generation DNA sequencing identified PDGFRB alterations in all cases of
myopericytomatosis and conventional myopericytoma tested (5 cases each),
including mutations in 4 cases of myopericytomatosis (N666K in 3; Y562-R565
deletion in 1 case) and 3 myopericytomas (Y562C, K653E, and splice acceptor
deletion in 1 case each), as well as low-level PDGFRB amplification in 2 cases of
myopericytomatosis and 4 myopericytomas. No BRAF, NOTCH, or GLI1 alterations were
detected. In summary, myopericytomatosis is a rare, strikingly diffuse, but
apparently benign variant of myopericytoma that typically involves superficial
soft tissue in adults with innumerable discrete microscopic myopericytomatous
nodules. The strongly activating PDGFRB mutation N666K is noted in
myopericytomatosis, but not in conventional myopericytoma, suggesting that PDGFRB
mutation status may account for their pathogenetic differences. As PDGFRB
alterations are present in myopericytoma/myopericytomatosis and infantile
myofibromatosis/myofibroma, these entities indeed lie within a histogenetic
continuum. Identification of PDGFRB alterations suggests tyrosine kinase
inhibition as a potential therapeutic strategy in myopericytic neoplasms if
needed.
PMID- 28505007
TI - AL Amyloidoma of the Skin/Subcutis: Cutaneous Amyloidosis, Plasma Cell Dyscrasia
or a Manifestation of Primary Cutaneous Marginal Zone Lymphoma?
AB - It is unclear whether AL amyloidoma of the skin/subcutis represents a distinct
entity, an indolent precursor of systemic amyloidosis, or a manifestation of
cutaneous marginal zone lymphoma (cMZL). We collected 10 cases of cutaneous AL
amyloidoma in order to better characterize the clinicopathologic features of this
elusive entity (M:F=4:6; median age: 62.5 y, range: 31 to 82 y). Nine patients
had a solitary nodule or plaque on the lower extremity (n=7), upper extremity
(n=1), or chin (n=1). One patient had an AL amyloidoma on the right thigh and a
second lesion on the right arm showing histopathologic features of cMZL without
amyloid deposits. Clinical investigations excluded relevant systemic disease in
all cases. Microscopically, dermal/subcutaneous deposits of amyloid were
associated with sparse to moderate perivascular infiltrates of lymphocytes and
monotypic plasma cells (7 with kappa and 3 with lambda light chain restriction).
The plasma cells expressed CD56 in one of 9 studied cases. One case was
characterized by a t(14;18)(q32;q21)/IGH-MALT1 translocation. Follow-up was
available in 8 cases. All remain systemically well after a median time of 86.5
months (range: 40 to 144 mo). Local recurrence of disease was observed in 3
patients. A fourth patient presented with a cMZL without amyloid deposits 8 years
after excision of the cutaneous AL amyloidoma. Although our series is small,
careful categorization and follow-up of the cases, together with updated
information in the literature, show clinical and biological links between AL
amyloidomas of the skin/subcutis and cMZL, suggesting that at least a subset of
cutaneous AL amyloidoma may represent an unusual manifestation of cMZL (cutaneous
mucosa-associated lymphoid tissue lymphomas).
PMID- 28505008
TI - Multinodular and Vacuolating Neuronal Tumor: A Rare Seizure-associated Entity.
AB - Multinodular and vacuolating neuronal tumor is a recently described seizure
associated entity with overlapping features of a malformative and neoplastic
process. We report a case of multinodular and vacuolating neuronal tumor in a 29
year-old man with a history of recent headaches and complex partial seizures.
Neuroimaging revealed a nonenhancing, T2 and T2 fluid-attenuated inversion
recovery hyperintense multinodular lesion in the right temporal lobe. Lesional
tissue demonstrated well-demarcated nodules of ganglioid cells with vacuolation
of both the perikarya and the fibrillary neuropil-like background. The ganglioid
cells showed weak cytoplasmic reactivity for synaptophysin and were nonreactive
for neurofilament and chromogranin. CD34-positive stellate cells were present
within the nodules. A 50-gene next-generation sequencing panel did not identify
any somatic mutations in genomic DNA extracted from the tumor.
PMID- 28505009
TI - A Novel Grading System Based on Tumor Budding and Cell Nest Size Is a Strong
Predictor of Patient Outcome in Esophageal Squamous Cell Carcinoma.
AB - The determination of prognosis in patients with esophageal squamous cell
carcinoma (ESCC) is primarily based on staging according to the TNM
classification, whereas conventional grading is of minor clinical importance
because of its deficiencies in prognostic patient stratification. Recently, a
novel, highly prognostic grading scheme based on budding activity and cell nest
size has been proposed for squamous cell carcinoma (SCC) of both pulmonary as
well as oral origin. In order to investigate the utility and transferability of
this approach to ESCC, we evaluated budding activity and cell nest size, as well
as other histomorphologic characteristics, in a cohort of 135 primarily resected
tumors and correlated the results with clinicopathologic and outcome parameters.
High budding activity and small cell nest size showed a strong association with
reduced overall, disease-specific, and disease-free survival (P<0.001,
respectively) in ESCC. The combination of both markers in a 3-step grading system
showed excellent prognostic separation of well-differentiated (G1), moderately
differentiated (G2), and poorly differentiated (G3) carcinomas (P<0.001). The
hazard ratio for disease-free survival in multivariate analysis under inclusion
of stage was 2.97 for G2 and 5.42 for G3 ESCC (P<0.001). World Health
Organization-based grading had no prognostic impact. Taken together, our data
prove the value of tumor budding and cell nest size as excellent outcome
predictors in ESCC and validate the utility of a previously established grading
scheme proposed for oral and pulmonary SCC in this tumor entity. Ultimately,
these combined efforts may result in a universal grading system for SCC
regardless of the site of origin.
PMID- 28505010
TI - Tackling immunomonitoring in gastrointestinal cancer.
AB - PURPOSE OF REVIEW: The growing awareness that the immune system is a key player
in the antitumoral response and the excellent clinical results achieved in some
settings with anti-programmed cell death 1 (PD1)/programmed death ligand 1 (PDL1)
and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) drugs has led to the
rise of immunotherapy as a supplement or an alternative to conventional cancer
treatment. The high costs associated with these therapies, their significant
toxicity and the need to understand and circumvent immune escape mechanisms raise
the urgent need for immunological assessment of therapy response. The study of
the immunological parameters before, during and after treatment is referred to as
immunomonitoring. This review discusses the current knowledge of immunomonitoring
markers in gastrointestinal cancers. RECENT FINDINGS: The last decade has seen a
collaborative effort to standardize the assays performed in clinical trials to
assess response to immunotherapy. Since then, multiple studies have been
conducted on blood samples, biopsies and surgical specimens to determine their
immunological profiles leading to the identification of several immunological
markers possessing a predictive value of response to treatment. SUMMARY: Future
research will focus on detangling the predictive value of immune markers in
different therapeutic models, and also to develop new noninvasive means to
monitor the immune response of patients. VIDEO ABSTRACT:
http://links.lww.com/COON/A20.
PMID- 28505011
TI - In-vitro assessment of the effect of dabigatran on thrombosis of adult and
neonatal plasma: comparisons using thromboelastography and microscopic
visualization of fibrin clot structure.
AB - : Thromboelastography (TEG) is a global assay used for evaluating features of
clot formation in vitro. Dabigatran is a reversible direct inhibitor of thrombin
that has not been studied in neonates using a sophisticated global assay, such as
TEG. Neonatal hemostasis differs from adult hemostasis in both quantitative and
qualitative characteristics. Our aim was to compare the TEG clotting profile of
neonatal and adult platelet-poor plasma when exposed to different concentrations
of dabigatran. We used commercially collected adult pooled plasma and neonatal
cord blood collected from placentas of healthy full term newborns. Platelet-poor
plasma was isolated, pooled, and frozen. Prior to experiment, plasma was thawed
and filtered. A reaction mixture of CaCl2, corn trypsin inhibitor, tissue factor,
and dabigatran in imidazole buffer was mixed with plasma in a TEG cup. Time to
clot initiation (R-time), speed of clot strengthening (alpha-angle), and maximum
clot strength (maximal amplitude) were measured. Scanning electron microscopy was
performed to evaluate fibrin clot structure. Without dabigatran, there was no
significant difference in TEG measurements between neonatal and adult samples.
However, neonatal plasma clotting with dabigatran had slower onset, slower speed,
and weaker clots that were more porous with thicker fibers, compared with adult
plasma clotting. Thus, neonatal plasma may be more sensitive to dabigatran as
assessed by our in-vitro TEG study.
PMID- 28505012
TI - CORRELATION OF CLINICAL AND STRUCTURAL PROGRESSION WITH VISUAL ACUITY LOSS IN
MACULAR TELANGIECTASIA TYPE 2: MacTel Project Report No. 6-The MacTel Research
Group.
AB - PURPOSE: To evaluate progression of macular telangiectasia Type 2 lesions and
their correlation with visual acuity. METHODS: An international multicenter
prospective study with annual examinations including best-corrected visual acuity
(BCVA), fundus photography, fluorescein angiography, and optical coherence
tomography images graded centrally. Mixed models were used to estimate
progression rates, and a generalized linear model to compute the relative risk of
BCVA loss, loss of ellipsoid zone (EZ) reflectivity, development of pigment
plaques, or neovascularization. RESULTS: One thousand and fourteen eyes of 507
participants were followed for 4.2 +/- 1.6 years. Best-corrected visual acuity
decreased 1.07 +/- 0.05 letters (mean +/- SE) per year. Of all eyes, 15% lost
>=15 letters after 5 years. Of the eyes without EZ loss, 76% developed a
noncentral loss. Of the eyes with noncentral loss, 45% progressed to central EZ
loss. The rate of BCVA loss in eyes with noncentral EZ loss at baseline was
similar to eyes without EZ loss. The rate of BCVA loss was significantly higher
in eyes with central EZ loss at baseline (-1.40 +/- 0.14 letters, P < 0.001).
CONCLUSION: Ellipsoid zone loss is frequently found in macular telangiectasia
Type 2 and is an important structural component reflecting visual function. Its
presence in the fovea significantly correlates with worse visual prognosis.
PMID- 28505013
TI - DISEASE EXPRESSION IN NONEXUDATIVE AGE-RELATED MACULAR DEGENERATION VARIES WITH
CHOROIDAL THICKNESS.
AB - PURPOSE: To investigate the relationship between subfoveal choroidal thickness
and disease manifestation in a series of eyes with nonexudative age-related
macular degeneration (AMD). METHODS: Retrospective study of eyes with
nonexudative AMD. The extracellular deposits present, drusen and subretinal
drusenoid deposits (SDD, pseudodrusen) along with a newly recognized form of
drusen, pachydrusen, were graded and compared with choroidal thickness as
determined by optical coherence tomography. Demographic and imaging information
was evaluated with descriptive statistics and generalized estimating equations.
RESULTS: There were 94 eyes of 71 patients, who had a mean age of 78.1 years.
Soft drusen alone were found in 45 eyes (47.9%) and subretinal drusenoid deposit
with or without drusen in 38 (40.4%). Pachydrusen, which were typically larger
than 125 MUm, often had an irregular outer contour, showed a scattered
distribution over the posterior pole and occurred in isolation or in groups of
only a few drusen were found in 11 (11.7%). The mean subfoveal choroidal
thickness in the soft drusen group was 227.9 MUm, in the subretinal drusenoid
deposit group 167.3 MUm, and in the pachydrusen group 419 MUm. The differences
between the groups were highly significant. CONCLUSION: Extracellular deposits,
subretinal drusenoid deposits and drusen, which are on either side of the retinal
pigment epithelium, respectively, are common in nonexudative AMD. A new form of
drusen presentation could be differentiated from typical soft drusen and was
associated with thicker choroids. Disease manifestation in nonexudative AMD seems
to be associated with choroidal thickness. Each of these has potential to lead to
specific forms of late AMD.
PMID- 28505014
TI - Validation of a smartphone auscultatory blood pressure kit Accutension XYZ-110 in
adults according to the ANSI/AAMI/ISO 81060-2: 2013 standard.
AB - OBJECTIVE: The aim of this study was to validate the accuracy of the Accutension
XYZ-110 blood pressure (BP) kit according to the American National Standards
Institute/Association for the Advancement of Medical
Instrumentation/International Organization for Standardization (ANSI/AAMI/ISO)
81060-2:2013 standard. PARTICIPANTS AND METHODS: Systolic blood pressure (SBP)
and diastolic blood pressure (DBP) were measured simultaneously on the same arm
in 85 Chinese adults (female : male=48 : 37) with a mean age of 43.2 years using
the mercury sphygmomanometer (two observers) and the Accutension XYZ-110 device
(one supervisor). The ANSI/AAMI/ISO 81060-2:2013 standard for the validation of
BP-measuring devices in adults was followed precisely. A total of 255 comparison
pairs were obtained for analysis. RESULTS: The mean device-observer difference in
the 255 separate BP data pairs was 2.45+/-2.24 mmHg for SBP and 0.69+/-2.09 mmHg
for DBP. The data were in accordance with the criterion 1 of the ANSI/AAMI/ISO
81060-2:2013 standard requirements (<=5+/-8 mmHg). In addition, the mean device
observer difference of the 85 participants was 2.45+/-1.47 mmHg for SBP and
0.69+/-1.36 mmHg for DBP. The device accuracy also fulfilled the criterion 2 with
the SD of less than or equal to 6.47 for SBP and less than or equal to 6.90 mmHg
for DBP. CONCLUSION: The Accutension XYZ-110 BP kit fulfilled the requirements of
the ANSI/AAMI/ISO 81060-2:2013 standard, and hence could be recommended for both
clinical and self/home BP measurement in adults.
PMID- 28505016
TI - The Contemporary Microbiology of Osteoarticular Infections in Young Children.
PMID- 28505015
TI - Virologic Response to First-line Efavirenz- or Nevirapine-based Antiretroviral
Therapy in HIV-infected African Children.
AB - BACKGROUND: Poorer virologic response to nevirapine- versus efavirenz-based
antiretroviral therapy (ART) has been reported in adult systematic reviews and
pediatric studies. METHODS: We compared drug discontinuation and viral load (VL)
response in ART-naive Ugandan/Zimbabwean children >=3 years of age initiating ART
with clinician-chosen nevirapine versus efavirenz in the ARROW trial. Predictors
of suppression <80, <400 and <1000 copies/mL at 36, 48 and 144 weeks were
identified using multivariable logistic regression with backwards elimination (P
= 0.1). RESULTS: A total of 445 (53%) children received efavirenz and 391 (47%)
nevirapine. Children receiving efavirenz were older (median age, 8.6 vs. 7.5
years nevirapine, P < 0.001) and had higher CD4% (12% vs. 10%, P = 0.05), but
similar pre-ART VL (P = 0.17). The initial non-nucleoside-reverse-transcriptase
inhibitor (NNRTI) was permanently discontinued for adverse events in 7 of 445
(2%) children initiating efavirenz versus 9 of 391 (2%) initiating nevirapine (P
= 0.46); at switch to second line in 17 versus 23, for tuberculosis in 0 versus
26, for pregnancy in 6 versus 0 and for other reasons in 15 versus 5. Early (36
48 weeks) virologic suppression <80 copies/mL was superior with efavirenz,
particularly in children with higher pre-ART VL (P = 0.0004); longer-term
suppression was superior with nevirapine in older children (P = 0.05). Early
suppression was poorer in the youngest and oldest children, regardless of NNRTI
(P = 0.02); longer-term suppression was poorer in those with higher pre-ART VL
regardless of NNRTI (P = 0.05). Results were broadly similar for <400 and <1000
copies/mL. CONCLUSION: Short-term VL suppression favored efavirenz, but long-term
relative performance was age dependent, with better suppression in older children
with nevirapine, supporting World Health Organization recommendation that
nevirapine remains an alternative NNRTI.
PMID- 28505017
TI - Septic Arthritis due to Streptococcus dysgalactiae Subspecies equisimilis in a
Healthy School Child.
PMID- 28505018
TI - The variation of the 5-hydroxytryptamine system between chronic unpredictable
mild stress rats and chronic fatigue syndrome rats induced by forced treadmill
running.
AB - The aim of this study was to observe the variation in the 5-hydroxytryptamine (5
HT) system between a chronic unpredictable mild stress (CUMS) model and a chronic
fatigue syndrome (CFS) model. The total distance, the crossing pieces, and
rearing times in the open-field test of the CUMS group and the CFS group were all
less than those of the control group to different degrees. The concentrations of
tryptophan, 5-HT, and 5-HIAA of the CUMS group were obviously lower than those of
the control group. In the CFS model, the concentrations of tryptophan, 5-HT, and
5-HIAA were obviously higher than those of the control group. The expressions of
tryptophan hydroxylase-2 (TPH-2) and 5-HT1A receptor in protein level and mRNA
level were also different among the three groups. The expressions of TPH-2 and 5
HT1A were higher in the CFS group than in the CUMS group. The expressions of TPH
2 and 5-HT1A receptor were lower in the CUMS group than in the control group. We
can find that in different situations of mood disorders, the variation of 5-HT
system may also be opposite.
PMID- 28505019
TI - What'S New in SHOCK, June 2017?
PMID- 28505020
TI - The Role of Thioredoxin-1 in Suppression Sepsis Through Inhibiting Mitochondrial
Induced Apoptosis in Spleen.
AB - Sepsis is a serious public health issue and the leading cause of death in
critically ill patients in intensive care units. Thioredoxin-1 (Trx-1) is a
protein of regulating redox, as well as a modulator of inflammation and
apoptosis. Our previous study reported that Trx-1 decreased endoplasmic reticulum
mediated inflammation involved in lung in a model of experimental sepsis.
However, its effect on mitochondrial-mediated apoptosis in spleen has not been
reported. We studied whether Trx-1 could prevent spleen cells apoptosis in
sepsis. In the present study, we showed that the apoptosis in spleen was
decreased in sepsis induced by cecal ligation and puncture (CLP) in Trx-1
overexpression transgenic (Tg) mice compared with wild-type mice. Colony forming
units in the peritoneal cavity and the level of procalcitonin in plasma were
significantly decreased in Trx-1 Tg mice 12 h after CLP. The expressions of c-jun
N-terminal kinase, Bax, caspase-9, and caspase-3 were increased in spleen, which
were suppressed in Trx-1 Tg mice. However, the decreased Bcl-2 expression in
sepsis was recovered in Trx-1 Tg mice. Our results suggest that overexpression of
Trx-1 provides protection against sepsis through suppressing mitochondria-induced
apoptosis pathway in spleen. This study may provide a new target for clinical
intervention, as well potential strategies for treatment of sepsis.
PMID- 28505021
TI - Use of a Short-Acting beta1 Blocker During Endotoxemia May Reduce Cerebral Tissue
Oxygenation if Hemodynamics are Depressed by a Decrease in Heart Rate.
AB - BACKGROUND: A decrease in heart rate (HR) using a short-acting beta blocker has
potential benefits in sepsis; however, depression of hemodynamics and reduction
of cerebral oxygenation may also occur in endotoxemia. METHODS: Seventeen swine
were allocated to landiolol or control groups. In the landiolol group, the dose
was sequentially changed from 0 to 40 to 200 MUg kg min, and stopped.
Hemodynamics, blood variables, and the cerebral tissue oxygenation index (TOI)
were recorded by near infrared spectroscopy at each dose. Lipopolysaccharide
(LPS) was then administered continuously at 1 MUg kg h after a 100 MUg bolus
administration. After 30 and 150 min, as two severity stages of endotoxemia
(endotoxemia 1 and 2), landiolol was administered as above and measurements were
made. In the control group, landiolol was not administered, but measurements were
made. RESULTS: LPS increased HR and landiolol decreased HR, with similar effects
in each endotoxemia stage. In endotoxemia 1, LPS decreased stroke volume (SV),
but landiolol restored SV to a value similar to that before endotoxemia, and did
not decrease cardiac output (CO), even at 200 MUg kg min. In contrast, landiolol
did not restore SV in endotoxemia 2, resulting in a decrease in CO and mean
arterial pressure, accompanied with a dose-dependent decrease in TOI.
CONCLUSIONS: A short-acting beta blocker has various hemodynamic effects in
endotoxemia. Use of a short-acting beta blocker during endotoxemia may reduce
cerebral tissue oxygenation if hemodynamics are depressed by a decrease in HR.
PMID- 28505024
TI - Autonomic Nervous System Pretransplant Malfunction Is a Powerful Predictor of
Survival After Allogeneic Hematopoietic Cell Transplantation.
AB - BACKGROUND: Autonomic nervous system function indexed by heart rate variability
(HRV) has shown prognostic value for mortality in various cardiovascular and
noncardiovascular diseases including cancer. The purpose of this study was to
evaluate an association between HRV and outcomes of allogeneic hematopoietic cell
transplantation (allo-HCT). METHODS: We prospectively measured HRV as a surrogate
pretransplant marker of autonomic nervous system activity in consecutive allo
HCTs with hematological diseases. RESULTS: We analyzed 112 allo-HCTs performed
between July 2011 and July 2013 in our center. Univariate analysis showed that
increased values of HRV components (low-frequency [LF] and high-frequency [HF]
spectral component), SD of normal-to-normal RR interval (SDNN), and squares of
the differences between adjacent normal-to-normal RR intervals (r-MSSD) were
significantly associated with decreased probability of overall mortality (hazard
ratio = 0.3 for LF, P < 0.001; hazard ratio = 0.3 for HF, P = 0.001; hazard ratio
= 0.6 for SDNN, P = 0.004; and hazard ratio = 0.5 for r-MSSD, P = 0.014). Among
these 4 indicators, the LF-added pretransplantation assessment of mortality,
hematopoietic cell transplantation-comorbidity index, and disease risk index
models showed the highest values of DeltaAkaike information criterion (16.5,
22.2, and 11.4, respectively). When stratified into quartiles of LF groups, 2
year overall survival was 92.9, 84.5, 59.7, and 33.2%, respectively (P < 0.001).
LF alone represented a better discriminating variable for the prediction of
mortality when compared with pretransplantation assessment of mortality,
hematopoietic cell transplantation-comorbidity index, and disease risk index. In
addition, from bivariate analyses, decreased LF was an independent and
significant factor for higher overall mortality in all models. CONCLUSIONS:
Indicators reflective of autonomic nervous system function might be a powerful
predictor of survival after allo-HCT.
PMID- 28505025
TI - A Rodent Model of Cardiac Donation After Circulatory Death and Novel Biomarkers
of Cardiac Viability During Ex Vivo Heart Perfusion.
AB - BACKGROUND: Organ donation after circulatory death (DCD) is increasingly being
used as a means of addressing the organ supply/demand mismatch in solid organ
transplantation. There is reluctance to use DCD hearts, due to an inability to
precisely identify hearts that have suffered irreversible injury. We investigated
novel biomarkers and clinically relevant endpoints across a spectrum of warm
ischemic times, before and during ex vivo heart perfusion (EVHP), to identify
features associated with a nonviable cardiac phenotype. METHODS: Donor rats
sustained a hypoxic cardiac arrest, followed by variable acirculatory standoff
periods (DCD groups). Left ventricular function, histochemical injury, and
differences in left ventricular gene expression were studied before, and during,
EVHP. RESULTS: As warm ischemic time exposure increased in DCD groups, fewer
hearts were functional during EVHP, and ventricular function was increasingly
impaired. Histochemical assessment identified severely injured hearts during
EVHP. A novel gene expression signature identified severely injured hearts during
EVHP (upregulation of c-Jun, 3.19 (2.84-3.60); P = 0.0014; HMOX-1, 3.87 (2.72
5.50); P = 0.0037; and Hsp90, 7.66 (6.32-9.27); P < 0.0001 in DCD20), and may be
useful in identifying high-risk hearts at the point of harvest (Hsp90).
CONCLUSIONS: We demonstrate that our preclinical model recapitulates the cardio
respiratory decompensation observed in humans, and that EVHP appears necessary to
unmask distinguishing features of severely injured DCD hearts. Furthermore, we
outline a clinically relevant multimodal approach to assessing candidate DCD
hearts. Novel mRNA signatures correlated with elevations in cardiac Troponin-I in
severely injured hearts during EVHP, and may also detect injury at the point of
harvest.
PMID- 28505026
TI - Combined Heart Lung Transplantation: An Updated Review of the Current Literature.
AB - Heart lung transplantation is a viable treatment option for patients with many
end-stage heart and lung pathologies. However, given the complex nature of the
procedure, it is imperative that patients are selected appropriately, and the
clinician is aware of the many unique aspects in management of this population.
This review seeks to describe updated organ selection policies, perioperative and
postoperative management strategies, monitoring of graft function, and clinical
outcomes for patients after combined heart-lung transplantation in the current
era.
PMID- 28505027
TI - Automated surveillance of healthcare-associated infections: state of the art.
AB - PURPOSE OF REVIEW: This review describes recent advances in the field of
automated surveillance of healthcare-associated infections (HAIs), with a focus
on data sources and the development of semiautomated or fully automated
algorithms. RECENT FINDINGS: The availability of high-quality data in electronic
health records and a well-designed information technology (IT) infrastructure to
access these data are indispensable for successful implementation of automated
HAI surveillance. Previous studies have demonstrated that reliance on stand-alone
administrative data is generally unsuited as sole case-finding strategy. Recent
attempts to combine multiple administrative and clinical data sources in
algorithms yielded more reliable results. Current surveillance practices are
mostly limited to single healthcare facilities, but future linkage of multiple
databases in a network may allow interfacility surveillance. Although prior
surveillance algorithms were often straightforward decision trees based on
structured data, recent studies have used a wide variety of techniques for case
finding, including logistic regression and various machine learning methods. In
the future, natural language processing may enable the use of unstructured
narrative data. SUMMARY: Developments in healthcare IT are rapidly changing the
landscape of HAI surveillance. The electronic availability and incorporation of
routine care data in surveillance algorithms enhances the reliability, efficiency
and standardization of surveillance practices.
PMID- 28505028
TI - Cytomegalovirus disease in hematopoietic stem cell transplant patients: current
and future therapeutic options.
AB - PURPOSE OF REVIEW: Allogeneic hematopoietic stem cell transplantation (allo-HSCT)
has become one of the standard treatment for hematological diseases. Although the
clinical outcome has improved significantly during the last decades, the
morbidity and mortality after allo-HSCT are still obstacles to cure. Out of major
morbidities, opportunistic virus infections such as cytomegalovirus (CMV)
infection are important complications, in particular in patients who received
human leukocyte antigen-mismatched HSCT. Here, we aim to summarize information
about current and future therapeutic options in CMV disease after allo-HSCT.
RECENT FINDINGS: Recently, not only new drugs but also adoptive T-cell therapy
are tested in the setting of clinical trials. CMV prophylaxis using letermovir
significantly reduced the incidence of CMV disease in comparison to placebo in a
phase III clinical trial. Meanwhile, adoptive T-cell therapies which are fully
adapted to good manufacturing practice (GMP) conditions are now available. A
recent multicenter study in Germany showed a promising result using Streptamer
isolated T-cell therapy. SUMMARY: With the recent development of CMV-targeted
therapy, treatment strategies of CMV infection would be further sophisticated in
the near future. VIDEO ABSTRACT: http://links.lww.com/COID/A19.
PMID- 28505029
TI - Treatment Options for Failed Back Surgery Syndrome Patients With Refractory
Chronic Pain: An Evidence Based Approach.
AB - STUDY DESIGN: A significant number of lumbar postsurgical patients continue to
suffer persistent pain and limited function and are termed to have "Failed back
surgery syndrome" (FBSS). This review evaluates clinical trial data for the
treatment of FBSS patients. OBJECTIVE: Using an evidence-based approach to
evaluate FBSS treatments will assist clinicians in choosing the most effective
options for FBSS patients. Furthermore, reducing the utilization of less
effective therapies may result in substantial financial savings for this patient
population. SUMMARY OF BACKGROUND DATA: Treatments for FBSS may be generally
categorized as physical therapy and exercise, medications, interventional
procedures, neuromodulation, and reoperation. Careful review and classification
of the level of evidence available for each category of treatment for FBSS
patients will help guide clinical decision-making. METHODS: A literature review
was performed for FBSS treatments. The publications were arranged hierarchically
according to the North American Spine Society's guidelines as randomized
controlled trials (RCTs), prospective studies, retrospective chart, and
systematic reviews. Book chapters, nonsystematic reviews, and expert opinions
were excluded. The review focused on studies with at least 20 FBSS patients and 6
month follow-up. RESULTS: Evidence is weak for medications and reoperation, but
strong for active exercise and interventional procedures such as adhesiolysis.
The strongest evidence for long-term treatment is for spinal cord stimulation
(SCS), showing favorable Level I RCT results compared with conventional medical
management and reoperation. In addition, high-frequency SCS at 10 kHz has
demonstrated superiority over traditional, low-frequency SCS for treating low
back and leg pain in a recent Level I RCT. CONCLUSION: Clinicians may
increasingly utilize levels of evidence during their evaluation of each FBSS
patient to render the best therapeutic plan, likely resulting in improved long
term pain control and reducing costs by avoiding less effective modalities. New
directions in SCS show promising results for the treatment of FBSS. LEVEL OF
EVIDENCE: 1.
PMID- 28505030
TI - Association Between Neurotrophic Factor Expression and Pain-Related Behavior
Induced by Nucleus Pulposus Applied to Rat Nerve Root.
AB - STUDY DESIGN: An experimental animal study. OBJECTIVE: To investigate the
relationship between pain-related behavior and the expression of neurotrophic
factors in the dorsal root ganglion (DRG) and spinal cord (SC) using a nucleus
pulposus (NP) rat model. SUMMARY OF BACKGROUND DATA: Neurotrophic factors are
released from activated glial cells and are associated with pain-related
behavior. Nerve growth factor (NGF) is a neurotrophic factor that is induced by
inflammation. METHODS: Rats were divided into an NP group (n = 94) and a sham
operated group (n = 46). NP harvested from the tail was applied to the left L5
DRG. Rats in the NP group were then divided into five subgroups: one non
treatment and four treatment groups. In the treatment groups, a dose of anti-NGF
antibody or phosphate-buffered saline was administered into the DRG. Behavioral
testing was performed to investigate the mechanical withdrawal threshold of the
left hind paw for all groups. Immunohistochemical localization of NGF,
phosphorylated p38 (p38), and brain-derived neurotrophic factor (BDNF) in the
DRGs and SCs was performed, and the numbers of immunoreactive (IR) cells were
counted. RESULTS: The withdrawal threshold in the nontreatment NP group was
significantly decreased for 35 days, and that of the middle- and high-dose
treatment rats was significantly higher than the phosphate-buffered saline group
values. In the DRG, NGF-IR, p38-IR, and BDNF-IR cells were increased for days 21.
In the SC, BDNF-IR, and p38-IR cells were increased from days 7 to 21.
CONCLUSION: In the DRG, NGF expression increased, mechanical thresholds were
reduced, and p38 and BDNF expression was increased in the NP group. p38 and BDNF
expression was increased in SC neurons during the same period. Inhibition of NGF
may be a potential treatment for neuropathic pain due to lumbar disc herniation.
LEVEL OF EVIDENCE: 5.
PMID- 28505031
TI - Povidone-iodine Solutions Inhibit Cell Migration and Survival of Osteoblasts,
Fibroblasts, and Myoblasts.
AB - STUDY DESIGN: In vitro laboratory study. OBJECTIVE: The purpose of this study was
to identify the effect of dilute povidone-iodine (PVI) solutions on human
osteoblast, fibroblast and myoblast cells in vitro. SUMMARY OF BACKGROUND DATA:
Dilute PVI wound lavage has been used successfully in spine and joint
arthroplasty procedures to prevent postoperative surgical site infection, but
their biologic effect on host cells is largely unknown. METHODS: Human primary
osteoblasts, fibroblasts, and myoblasts were expanded in cell culture and
subjected to various concentrations of PVI (0%, 0.001%, 0.01%, 0.1%, 0.35%, 1%)
for 3 minutes. To assess the effect of PVI on cell migration, a scratch assay was
performed, in which a "scratch" was made by a standard pipette tip in a cell
monolayer following PVI exposure, and time to closure of the scratch was
evaluated. Cell survival and proliferation was measured 48 hours post-PVI
exposure using a cell viability and cytotoxicity assay. RESULTS: Closure of the
scratch defect in all cell monolayers was achieved in <24 hours in untreated
controls and following exposure to PVI concentrations <0.1%. The scratch defect
remained open indefinitely following exposure to PVI concentrations of >=0.1%.
PVI concentrations <0.1% did not have significant effect on survival rates
compared with control for all cell types. Cells exposed to PVI >= 0.1% had cell
survival rates of less than 6% (P < 0.05). CONCLUSIONS: Clinically used
concentration of PVI (0.35%) exerts a pronounced cytotoxic effect on osteoblasts,
fibroblast, and myoblasts in vitro. Further investigation is required to
systematically study the effect of PVI on tissue healing in vivo and also
determine a safe and clinically potent concentration for PVI lavage. LEVEL OF
EVIDENCE: N/A.
PMID- 28505032
TI - Do preventive interventions for children of mentally ill parents work? Results of
a systematic review and meta-analysis.
AB - PURPOSE OF REVIEW: The transgenerational transmission of mental disorders is one
of the most significant causes of psychiatric morbidity. Several risk factors for
children of parents with mental illness (COPMI) have been identified in numerous
studies and meta-analyses. RECENT FINDINGS: Many interventions have been
developed for this high-risk group, but data about their efficacy are
heterogeneous. SUMMARY: The current meta-analysis reports on 96 articles
including 50 independent samples from randomized controlled trials quantifying
effects of preventive interventions for COPMI. Random effect models resulted in
small, though significant Effect Sizes (ES) for programs enhancing the mother
infant interaction (ES = 0.26) as well as mothers' (ES = 0.33) and children's (ES
= 0.31) behavior that proved to be stable over the 12-month follow-up, except for
infants' behavior. Interventions for children/adolescents resulted in significant
small effects for global psychopathology (ES = 0.13), as well as internalizing
symptoms (ES = 0.17), and increased significantly over time, with externalizing
symptoms reaching significance in the follow-up assessments as well (ES = 0.17).
Interventions addressing parents and children jointly produced overall larger
effects. Higher study quality was associated with smaller effects. There is a
dearth of high quality studies that effectively reduce the high risk of COPMI for
the development of mental disorders.
PMID- 28505033
TI - Minimally invasive brow lifting techniques.
AB - PURPOSE OF REVIEW: Aesthetic concerns about upper eyelid and brow position are
very common in ophthalmic practice. Management of brow descent and devolumization
requires an approach customized to each patient taking into consideration
preoperative examination and patient desires. This article will review several
minimally invasive techniques that can be used to address the needs of patients
with mild-to-moderate brow ptosis. RECENT FINDINGS: Recent publications describe
and analyse efficacy of several variations of browpexy techniques. SUMMARY:
Browpexy techniques provide a minimally invasive way to provide stabilization and
modest elevation of the lateral brow. They can enhance outcomes of upper eyelid
surgery in patients with both functional and cosmetic brow ptosis, who desire to
avoid the cost and morbidity of more formal brow lifting techniques.
PMID- 28505034
TI - Pediatric corneal transplants.
AB - PURPOSE OF REVIEW: Pediatric keratoplasty poses unique challenges in clinical and
surgical management. However, successful transplantation can afford a child
vision in an otherwise poorly seeing eye. This review will provide an update on
recent advances in pediatric keratoplasty. RECENT FINDINGS: Although children who
receive corneal transplants remain at increased risk of rejection, infection, and
graft dehiscence compared with adult corneal transplant recipients, new surgical
techniques, and advances in clinical management have led to better outcomes.
Surgical modifications in penetrating keratoplasty (PKP) offer increased
stabilization of the delicate pediatric eye. Lamellar surgery, including
endothelial keratoplasty and deep anterior lamellar keratoplasty, can target
specific diseased tissue in children with potentially fewer complications. The
keratoprosthesis can be used successfully in children when the chance of success
with PKP is especially low. SUMMARY: As our knowledge of prognostic indicators
and surgical techniques continues to grow, we can offer children safer and more
targeted surgeries for some of the most challenging corneal diseases. Ultimately,
successful transplantation with long-term graft survival can be obtained by a
multidisciplinary approach, with care across ophthalmic specialties, and a
commitment to long-term follow-up by the patient's family.
PMID- 28505036
TI - Editorial.
PMID- 28505035
TI - Invasive fungal sinusitis: treatment of the orbit.
AB - PURPOSE OF REVIEW: To summarize diagnostic techniques for invasive fungal
rhinosinusitis and provide a review of treatment options once disease has spread
to the orbit. RECENT FINDINGS: Improved imaging criteria, polymerase chain
reaction and other serologic tests show promise in advancing our ability to
accurately diagnose invasive fungal disease. Currently, there exists three
treatment options for infected orbital tissue: exenteration, conservative
debridement and transcutaneous retrobulbar injection of amphotericin B.
Exenteration, the most frequently reported intervention, has not been proven to
enhance survival. Conservative debridement and transcutaneous retrobulbar
injection of amphotericin B are increasingly considered reasonable first-line
options. SUMMARY: Although investigative tools are improving, invasive fungal
rhinosinusitis can still pose a diagnostic challenge. No one treatment option for
the orbit has been proven superior to another. Therefore, it is justified to
initiate therapy by prioritizing less morbid procedures. If deterioration is
continually noted, more invasive interventions can then be employed. The
treatment algorithm established at our institution is provided.
PMID- 28505037
TI - Getting ready for the first robotic prostatectomy, from basics to real practice.
AB - PURPOSE OF REVIEW: Robot-assisted radical prostatectomy (RARP) has been embraced
by urologists and has become a treatment standard in many countries already.
Learning how to perform a RARP is challenging and has not yet been standardized.
The current review summarizes the latest concepts regarding the most effective
way of training for RARP. RECENT FINDINGS: The strategy to learn RARP should
comprise didactic activities, skills lab training, participating in surgeries and
mentorship. Skills lab and virtual simulators are valuable tools to develop
manual abilities and to overcome the initial technical learning curve.
Participating in surgeries is crucial for familiarization with the robot
installation, steps of the surgical procedure and is essential for
troubleshooting. Mentorship improves learning and is the safest way to initiate
real practice. Innate and individual background variances were suggested to
influence the learning process; however, there is paucity of robust evidence
correlating previous surgical experience and, for example videogame playing with
faster learning of RARP. Structured curricula were proposed to orient the
training for robotic surgery; currently, only one is focused exclusively on
urology. SUMMARY: Systematic training is the most effective way to learn and
surpass the possibly intense learning curve of RARP. Training activities should
focus on developing cognitive and manual abilities. The existing curricula for
robotic surgery training still require constant refinement; however, they offer
good and structured guidance to train for RARP.
PMID- 28505038
TI - Editorial.
PMID- 28505039
TI - Patient-reported outcome measures in urology.
AB - PURPOSE OF REVIEW: Many urologic treatments have similar clinical outcomes,
necessitating alternative methods to discriminate between options. Patient
reported outcome measures (PROMs) have become the new standard for evaluating the
patient experience, and their use has drastically increased over the past decade.
The purpose of this review is to discuss the status of PROMs in urology,
highlight commonly used tools and address their future direction. RECENT
FINDINGS: An increasing number of urology-specific PROMs tools have been
developed and validated. An increased focus on patient-centered care has provided
an impetus for their rise in use. Implementation of PROMs has transitioned from
being primarily descriptive in nature to producing actionable findings. Many
PROMs are now implemented in daily clinical practice. The future of PROMs will
involve new instrument development, integration into clinical practice and the
use of PROMs as performance measures. SUMMARY: PROMs are effective tools for
characterizing symptom burden and health-related quality of life. With increasing
clinical implementation, PROMs are playing an increasing role in patients'
clinical decision-making.
PMID- 28505040
TI - News and views - June 2017.
PMID- 28505042
TI - Dissecting Leapfrog: How Well Do Leapfrog Safe Practices Scores Correlate With
Hospital Compare Ratings and Penalties, and How Much Do They Matter?
PMID- 28505041
TI - The Potential Return on Public Investment in Detecting Adverse Drug Effects.
AB - BACKGROUND: Many countries lack fully functional pharmacovigilance programs, and
public budgets allocated to pharmacovigilance in industrialized countries remain
low due to resource constraints and competing priorities. OBJECTIVE: Using 3 case
examples, we sought to estimate the public health and economic benefits resulting
from public investment in active pharmacovigilance programs to detect adverse
drug effects. RESEARCH DESIGN: We assessed 3 examples in which early signals of
safety hazards were not adequately recognized, resulting in continued exposure of
a large number of patients to these drugs when safer and effective alternative
treatments were available. The drug examples studied were rofecoxib,
cerivastatin, and troglitazone. Using an individual patient simulation model and
the health care system perspective, we estimated the potential costs that could
have been averted by early systematic detection of safety hazards through the
implementation of active surveillance programs. RESULTS: We found that earlier
drug withdrawal made possible by active safety surveillance would most likely
have resulted in savings in direct medical costs of $773-$884 million for
rofecoxib, $3-$10 million for cerivastatin, and $38-$63 million for troglitazone
in the United States through the prevention of adverse events. By contrast, the
yearly public investment in Food and Drug Administration initiated population
based pharmacovigilance activities in the United States is about $42.5 million at
present. CONCLUSION: These examples illustrate a critical and economically
justifiable role for active adverse effect surveillance in protecting the health
of the public.
PMID- 28505043
TI - Response to Letter to the Editor Regarding, Dissecting Leapfrog: How Well Do
Leapfrog Safe Practices Score Correlate With Hospital Compare Ratings and
Penalties, and How Much Do They Matter?
PMID- 28505044
TI - New technological devices for the assessment of systemic inflammation in the
primary prevention of cardiovascular disease.
AB - PURPOSE OF REVIEW: The prediction of cardiovascular disease (CVD) events is of
strategic importance for the primary prevention of one of the big killers in the
world. Predictive models have a history of decades, but still the desired
accuracy is not reached by any of the existing models. The inclusion of
inflammatory factors in the models did not increase their accuracy. In this
review, we discuss the possible reasons for that failure and we propose a
paradigm shift. RECENT FINDINGS: Systemic inflammation is a very volatile
phenomenon. The blood concentration of inflammatory biomarkers may change
considerably in one individual with a timescale of seconds. Sudden changes in
environmental conditions can trigger rapid modifications in the inflammatory
profile of an individual. In routine clinical practice, the blood tests for
inflammation are carried out at one point in time, not in standard environmental
conditions, and are therefore inadequate. SUMMARY: We have to direct CVD research
toward the understanding of the synchronic relationship between external
environmental conditions and internal physiological reactions. CVD risk
assessment must be carried out by using continuous real-time monitoring of
external and internal parameters together, something that may become possible
with the advent of new technological devices.
PMID- 28505045
TI - Resistant hypertension in 2017.
AB - PURPOSE OF REVIEW: Hypertension (HTN) is a ubiquitous condition and cause for
significant morbidity and mortality. Over 400 000 deaths in the United States are
related to HTN every year, more than all the Americans who died through all of
World War II. As many as half the patients with HTN in the United States have
resistant HTN, a blood pressure greater than 140/90 mmHg despite three
medications including a diuretic. It appears that the prevalence of HTN and
resistant HTN is increasing over time. There is a dire need for newer therapies
that may reduce or eliminate the need for multiple pharmacologic agents, thus
helping with compliance and reducing the possibility of their adverse events.
RECENT FINDINGS: The current review summarizes the techniques and results
reported in recent studies utilizing renal denervation technologies from the
original Symplicity Trials to newer multipolar electrodes being used for optimal
denervation. We also report the early experience with noninvasive renal
denervation. Endovascular carotid body stimulation is also being investigated for
resistant HTN. Renovascular HTN remains an underlying cause for resistant HTN,
and revascularization may prove to be an effective treatment for many of these
patients. SUMMARY: A multipronged approach utilizing lifestyle modification,
pharmacologic therapy and tailored endovascular treatments may be the algorithm
to treat the growing cohort of resistant HTN. However, most of the endovascular
treatments remain to be validated, and renal revascularization for renovascular
HTN has been set back by recent studies that did not appear to target the real
renovascular cohort.
PMID- 28505046
TI - South Asians: why are they at a higher risk for cardiovascular disease?
AB - PURPOSE OF REVIEW: We comment on the high prevalence of cardiovascular disease
(CVD) in South Asians (SA). The effect of various risk factors, for example
biochemical, genetic, lifestyle, socioeconomic factors and psychosocial stress on
CVD risk is discussed. RECENT FINDINGS: 'Prediabetes' is common in SA, but its
relationship with coronary artery disease (CAD) is not significant unlike for the
white population. At the same time, 'prediabetes' in SA is associated with an
increased risk for cerebrovascular disease (CeVD). The differentiating factor
could be the high lipids in Europeans and their relationship to CAD. Likewise,
higher diastolic blood pressure in SA may explain the risk of CeVD. Small, dense,
low-density lipoprotein (LDL), low high-density lipoprotein-cholesterol (HDL-C)
concentration and high triglycerides may contribute to atherosclerosis.
Thrombotic factors such as increased levels of plasminogen activator inhibitor,
fibrinogen, lipoprotein (a) and homocysteine have been shown to be associated
with increased CVD. Impaired cerebrovascular autoregulation and sympathovagal
activity, increased arterial stiffness and endothelial dysfunction may increase
CVD risk further. In addition, environmental and dietary factors may exaggerate
the unfavourable cardiovascular profile through genetic factors. SUMMARY: The
implications of the findings suggest comprehensive screening of SA for CVD.
Cultural differences should be considered while designing prevention strategies
specifically targeting barriers for uptake of preventive service.
PMID- 28505047
TI - Advances in the management of dyslipidemia.
AB - PURPOSE OF REVIEW: Cardiovascular disease is the leading cause of morbidity and
mortality in the United States and therapies aimed at lipid modification are
important for the reduction of cardiovascular risk. There have been many exciting
advances in lipid management over the recent years. This review discusses these
recent advances as well as the direction of future studies. RECENT FINDINGS:
Several recent clinical trials support low-density lipoprotein cholesterol (LDL
c) reduction beyond maximal statin therapy for improved cardiovascular outcomes.
Ezetimibe reduced LDL-c beyond maximal statin therapy and was associated with
improved cardiovascular outcomes for high-risk populations. Further LDL-c
reduction may also be achieved with proprotein convertase subtilisin/kexin type-9
(PCSK9) inhibition and a recent trial, Further Cardiovascular Outcomes Research
with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER), was the first to
show reduction in cardiovascular events for evolocumab. Additional outcome
studies of monoclonal antibody and RNA-targeted PCSK9 inhibitors are underway.
Quantitative high-density lipoprotein cholesterol (HDL-c) improvements have
failed to have clinical impact to date; most recently, cholesteryl ester transfer
protein inhibitors and apolipoprotein infusions have demonstrated disappointing
results. There are still ongoing trials in both of these areas, but some newer
therapies are focusing on HDL functionality and not just the absolute HDL-c
levels. There are several ongoing studies in triglyceride reduction including
fatty acid therapy, inhibition of apolipoprotein C-3 or ANGTPL3 and peroxisome
proliferator-activated receptor-alpha agonists. SUMMARY: Lipid management
continues to evolve and these advances have the potential to change clinical
practice in the coming years.
PMID- 28505048
TI - Long-term Follow-up of Adolescents Treated for Rumination Syndrome in an
Inpatient Setting.
AB - OBJECTIVES: Although several studies have demonstrated the short-term benefit of
the behavioral treatment of rumination syndrome, few have investigated the long
term outcomes. Studies reporting long-term benefit have involved combined
pediatric and adult samples or have examined outcomes of patients involved in
various types of treatment. The purpose of the present study was to examine
several aspects of long-term outcome in adolescent patients who took part in the
same intensive, interdisciplinary, inpatient behavioral treatment approach.
METHODS: Self-report measures were completed by 47 adolescent patients (mean age
= 15.9) around 1 year or more from discharge from our inpatient program. Measures
indexed changes in rumination, medical outcomes (eg, use of supplemental
nutrition), somatic symptoms, and quality of life. RESULTS: Most patients
reported continued improvement in their rumination over time, with 20% reporting
cessation of rumination for at least 6 months. The majority of patients no longer
required supplemental nutrition and reported improvements in somatic symptoms and
quality of life. Patients who reported greater improvement in rumination also
reported more significant improvements in their somatic symptoms and quality of
life. CONCLUSIONS: Intensive behavioral treatment of rumination syndrome leads to
long-term improvement in rumination as well as other related factors, including
somatic symptoms and quality of life.
PMID- 28505049
TI - Perceived Impairment in Sports Participation in Adolescents With Inflammatory
Bowel Diseases: A Preliminary Examination.
AB - OBJECTIVE: Physical activity (PA) is important for adolescents with inflammatory
bowel diseases (IBDs) given the increased risk of developing osteoporosis and the
increased risk of IBD-related complications among those with IBD and obesity.
Symptoms such as fatigue, abdominal pain, nausea, and frequent bowel movements
can interfere with PA. Sports participation is an important source of PA for
adolescents; however, the extent to which IBD interferes with sports
participation is unstudied. The present study aimed to examine demographic,
health-related, physical, and psychosocial correlates of perceived impairment in
sports participation. METHOD: Seventy-six adolescents (M[SD] = 14.5 [1.8] years,
45% girls) completed surveys of perceived impairment in sports participation,
demographics, physical health, and psychosocial health. Physicians rated disease
activity at enrolment. All participants were diagnosed with IBD for at least a
year and prescribed a daily oral medication. RESULTS: Nearly half of participants
reported at least occasional interference in sports participation because of
their IBD. Active disease (P = 0.014), older age (P = 0.006), and poorer disease
specific quality of life, and quality of life in physical health and psychosocial
domains were associated with greater impairment in sports participation in
bivariate analyses (P < 0.001). In regression analyses, systemic disease-related
symptoms, body image concerns, and older age emerged as the strongest predictors
of impairment in sports participation (P < 0.05). CONCLUSIONS: Older adolescents,
those with greater systemic symptoms, and those with poorer body image may be
particularly at risk for impairment in sports participation. Addressing barriers
to sports participation may be a useful strategy in enhancing PA in this patient
group.
PMID- 28505051
TI - Nutritional Benefit of Recycling of Bowel Content in an Infant With Short Bowel
Syndrome.
PMID- 28505050
TI - Unsedated In-office Transgastrostomy Esophagoscopy to Monitor Therapy in
Pediatric Esophageal Disease.
AB - Monitoring therapy in esophageal inflammatory disorders such as eosinophilic
esophagitis and reflux esophagitis often requires frequent endoscopic evaluation.
We recently reported the effective use of unsedated in-office transnasal
esophagoscopy that significantly decreased costs and anesthetic exposure
associated with pediatric esophagoscopy in eosinophilic esophagitis. Here we
report a series of pediatric patients with esophagitis with gastrostomy tubes who
underwent unsedated transgastrostomy esophagoscopy (TGE) in an office setting.
Nine patients (ages 16 months-21 years) tolerated TGE without significant adverse
events. Biopsy specimens were adequate for evaluation. This series confirms that
unsedated in-office TGE can be used to successfully obtain mucosal biopsies to
monitor esophageal inflammatory conditions in children without the use of
sedation.
PMID- 28505052
TI - Beyond Efficacy: The Acceptability of Antidepressant Treatment to Patients with
Inflammatory Bowel Disease.
PMID- 28505053
TI - Relationship Between Patient Knowledge and Medication Adherence in Inflammatory
Bowel Disease.
PMID- 28505054
TI - The Experience of Living With an Ileoanal Pouch: An Interpretative
Phenomenological Analysis.
AB - The purpose of this study was to explore the lived experiences of individuals
living with an ileoanal pouch. A qualitative, phenomenological methodology was
used to elicit detailed accounts of the impact of living with an ileoanal pouch.
Ten individuals having an ileoanal pouch, formed as a consequence of ulcerative
colitis, participated in the study. Semistructured interviews were conducted and
analyzed using interpretative phenomenological analysis. The following 4 themes
emerged from the analysis: "a flood of emotions"; "changed body image"; "changes
in lifestyle"; and "intimacy and sexual relationships." Participants indicated
that their quality of life after surgery has improved because they were no longer
suffering from the devastating symptoms of ulcerative colitis. However, a
considerable number of these participants disclosed that they are still living a
restricted lifestyle and reported profound changes not only in their physical
self but also in their social and sexual relationships. By acknowledging these
experiences, healthcare professionals have the potential to improve the
psychological, sexual, and social care that these individuals receive.
PMID- 28505055
TI - GASTRIC INJURY FOLLOWING NASOGASTRIC INTUBATION: A Case Report.
PMID- 28505056
TI - Relationship Between Psychological Safety and Reporting Nonadherence to a Safety
Checklist.
AB - Patient safety checklists are ubiquitous in health care. Nurses bear significant
responsibility for ensuring checklist adherence. To report nonadherence to a
checklist and stop an unsafe procedure, a workplace climate of psychological
safety is needed. Thus, an analysis of organizational data was conducted to
examine the relationship between psychological safety and reports of nonadherence
to the central line bundle checklist. Results showed varied perceptions of
psychological safety but no relationship with nonadherence. Considerations for
this finding and assessing psychological safety are provided.
PMID- 28505057
TI - Automated Medication Error Risk Assessment System (Auto-MERAS).
AB - This study developed the Automated Medical Error Risk Assessment System (Auto
MERAS), which was incorporated into the electronic health record system. The
system itself maintained high predictive validity for medication errors at the
area under the receiver operating characteristic curves of above 0.80 at the time
of development and validation. This study has found possibilities to predict the
risk of medication errors that are sensitive to situational and environmental
risks without additional data entry from nurses.
PMID- 28505058
TI - Organizational, Regional, and Community Factors Determining Protocol Compliance
for Patients With Acute Myocardial Infarction.
AB - This study examined factors determining hospital compliance to Hospital Quality
Alliance's protocol for patients with myocardial infarction. Using a spatially
matched sample of 132 Magnet and 264 non-Magnet hospitals, multivariate
regressions determined significant hospital characteristics associated with
compliance per Hospital Quality Alliance protocol. Adherence to the Hospital
Quality Alliance protocols varied widely by hospital characteristics. Registered
nurse staffing/bed was a key factor determining patient care quality variation.
Quality of care practices such as protocol compliance should be measured and
examined separately.
PMID- 28505059
TI - Creation of an Adult Observation Unit: Improving Outcomes.
AB - A growing segment of patients in hospitals are considered outpatients, classified
as observation. These patients neither have the severity of illness nor the
intensity of service to qualify as inpatients, yet are not well enough to be
discharged. Hospitals have created observation units to address the clinical
needs of this growing patient type to provide care in the right setting by
managing emergency department throughput and utilizing the most efficient
staffing resources. This article describes the change processes and improvements
in quality, length of stay, and patient satisfaction, which occurred following
the implementation of an adult observation unit.
PMID- 28505060
TI - The APRN Role in Changing Nursing Home Quality: The Missouri Quality Improvement
Initiative.
PMID- 28505061
TI - Novel OFD1 frameshift mutation in a Chinese boy with Joubert syndrome: a case
report and literature review.
AB - Joubert syndrome (JBTS) is a clinically and genetically heterogeneous group of
ciliopathy with a key diagnostic feature of 'molar tooth sign' in brain MRI. So
far, over 20 causative genes have been identified, but only one gene (OFD1)
results in X-linked Joubert syndrome 10 (JBTS10). Six mutations in the OFD1 gene
have been found to cause JBTS10. In this study, we identified a novel OFD1
mutation of c.2843_2844 delAA (p.Lys948ArgfsX) in a 3-month-old boy with a 'molar
tooth sign' and clinical features of JBTS using targeted exome next-generation
sequencing. The de-novo OFD1 mutation in exon 21 leads to a frameshift mutation
generating a prematurely truncated protein and is predicted to partly reduce the
function of the OFD1 protein. Our study expands the genotype-phenotype spectrum
in JBTS and will have applications in prenatal and early diagnosis of the
disorder. This is the first report of the OFD1 mutation causing JBTS in a Chinese
population.
PMID- 28505062
TI - Relationships between depression and anxiety symptoms scores and blood pressure
in young adults.
AB - BACKGROUND: Depression and anxiety are risk factors for cardiovascular disease,
but their relationship to blood pressure (BP) is less clear. Age-related
comorbidity and lifestyle factors may confound these relationships. This study
aimed to assess the relationships among BP, depression and anxiety symptom scores
and self-reported history of depression in young adults. METHOD: Data on 1014
participants aged 20 years from the Western Australian Cohort (Raine) Study were
analyzed for cross-sectional associations between clinic BP and Depression,
Anxiety, Stress Scale questionnaire scores or a reported history of depression,
accounting for relevant confounders. RESULTS: Multivariable adjusted analyses
showed an inverse relationship between SBP with depression (coefficient = -0.10;
P = 0.012) and anxiety (after excluding two outliers with SBP > 156 mmHg,
coefficient = -0.13; P = 0.018) scores, independent of sex, BMI, female hormonal
contraceptive use, alcohol consumption, birth weight and maternal hypertension in
pregnancy. SBP was 1.6 mmHg lower for 2 SD (16 units) increase in depression
score. There was an inverse association between self-reported history of
depression (15.8% of participants) and SBP (coefficient = -1.91; P = 0.023), with
an interaction with increasing BMI (interaction coefficient = -0.43; P = 0.002)
enhancing this difference. CONCLUSION: Our findings show that SBP in young adults
is inversely associated with depression and anxiety scores, independent of a
range of lifestyle confounders. Despite a positive association between BMI and
BP, adiposity enhanced the inverse association between self-reported history of
depression and SBP. These findings contrast with the predisposition of depressed
participants to cardiovascular disease in later life when decades of unhealthy
lifestyle changes may dominate.
PMID- 28505063
TI - Retinal vessel metrics: normative data and their use in systemic hypertension:
results from the Gutenberg Health Study.
AB - PURPOSE OF REVIEW: In-vivo measurement of retinal vascular calibers may be used
as a tool to study the pathophysiology and clinical status of the
microvasculature of the retina. The aim of this study was to generate normative
data for retinal vessel parameters, and to evaluate the clinical relevance in
systemic hypertension. METHODS: Fundus photographs from 4309 participants of the
Gutenberg Health Study were assessed using the 'retinal vessel analyzer' software
(IMEDOS). We generated age and sex-specific nomograms in a disease-free
subpopulation of 890 participants for determining the central retinal arteriolar
equivalent (CRAE), the central retinal venular equivalent, and the arteriovenous
ratio (AVR). RESULTS: Women had higher values of CRAE, central retinal venular
equivalent, and AVR than men, and the decrease in measures with increasing age
was less steep in women than in men. Systemic hypertension was associated with
lower values [odds ratio (OR), 95% confidence interval (CI) referring to area
below the 5% percentile] of AVR (men: OR 2.41, 95% CI 1.669-3.490, P < 0.001;
women: OR 3.01, 95% CI 2.126-4.268, P < 0.001) and CRAE (men: OR 2.60, 95% CI
1.563-4.326, P < 0.001, women: OR 3.00, 95% CI 2.004-4.487, P < 0.001). Both
median CRAE and AVR were lower in participants with uncontrolled hypertension
(172.28, range 83.05-251.04; and 0.81, range 0.56-1.04) versus those with
screening-detected hypertension (175.72, range 101.23-222.09, P < 0.001; and
0.82, range 0.64-1.05, P = 0.001), and versus those with controlled (179.10,
range 108.19-221.92, P < 0.001; and 0.84, range 0.60-1.08, P < 0.001)
hypertension. CONCLUSION: The study provides sex and age-specific normative data
for retinal vasculature. Persons with untreated or insufficiently treated
hypertension are more likely to have retinal vessel equivalents outside the
reference range.
PMID- 28505064
TI - Changes in renal artery dimensions are associated with clinical response to
radiofrequency renal denervation: a series of studies using quantitative
angiography and intravascular ultrasound.
AB - OBJECTIVE: Renal denervation (RDN) can cause focal (notches) and global (spasms)
changes in renal artery dimensions. We quantified these changes and related them
to renal norepinephrin tissue content in animals and to blood pressure (BP)
changes in patients. METHODS: We measured renal artery dimensions pre-RDN and
post-RDN, utilizing quantitative renal angiography (QRA) in a porcine model and
in a retrospective patient cohort, and intravascular ultrasound (IVUS) in a
prospective patient cohort. Focal and global measurements were minimum and mean
diameter/area/volume with QRA, minimum lumen/vessel/wall area and volume with
IVUS. BP was assessed with 24-h ambulatory monitoring, norepinephrin content with
liquid chromatography. RESULTS: In 36 pigs treated unilaterally with RDN,
norepinephrin content of the treated right kidney was 48.2% of the untreated left
kidney. QRA measurements following RDN were associated with norepinephrin content
only of the (treated) right kidney. In the human QRA study (n = 43 patients),
mean 24-h BP fell by 8/4 and 12/6 mmHg at 1 and 12 months, respectively. More
pronounced changes in QRA measurements were associated with a more pronounced BP
drop. In multiple regression models, the change in minimum diameter was
independently associated with BP changes at 12 months. In the prospective IVUS
study (n = 17 patients), a larger decrease in minimum lumen/vessel area and
larger increase of wall area/volume were associated with a larger BP drop.
CONCLUSION: Focal and global changes in renal arteries following RDN can be
quantified, using QRA or IVUS, and may serve as markers of a successful
procedure.
PMID- 28505065
TI - Arterial reservoir characteristics and central-to-peripheral blood pressure
amplification in the human upper limb.
AB - BACKGROUND: Arterial reservoir characteristics are related to blood pressure (BP)
and independently predict cardiovascular events. It is unknown if arterial
reservoir characteristics are modified from the central-to-peripheral large
arteries and whether there is a contributory role to BP amplification. The aim of
this study was to assess central-to-peripheral changes in arterial reservoir
characteristics and determine associations with BP. METHODS: Reservoir pressure
(RP) and excess pressure (XSP) were derived from intra-arterial BP waveforms
among 51 participants (aged 63 +/- 13 years, 63% men) undergoing clinically
indicated cardiac angiography. BP waveforms were recorded in the ascending aorta,
brachial (mid-humerus) and radial (wrist) arteries via catheter pull-back.
RESULTS: There was no significant difference in RP between arterial sites (54 +/-
15, 53 +/- 15 and 52 +/- 17 mmHg for the aorta, brachial and radial artery,
respectively; P = 0.68). Conversely, XSP increased stepwise from the aorta to the
brachial and radial arteries (24 +/- 11, 42 +/- 14 and 53 +/- 16 mmHg; P <
0.001), as did SBP (134 +/- 18, 141 +/- 16 and 146 +/- 19 mmHg; P = 0.004). There
were highly significant associations between RP and SBP at all arterial sites (r
= 0.821, 0.649 and 0.708; P < 0.001 for all), but the strength of associations
between peak XSP and SBP increased significantly from the aorta to the radial
artery (r = 0.121 and 0.508; z = 3.04; P = 0.004). CONCLUSION: Arterial reservoir
characteristics are modified through the large arteries of the upper limb.
Although RP remains relatively constant, XSP increases significantly and is
highly related to BP (SBP and pulse pressure) amplification. These data provide a
new understanding on arterial reservoir characteristics and large-artery BP
physiology.
PMID- 28505066
TI - Routine urinary detection of antihypertensive drugs for systematic evaluation of
adherence to treatment in hypertensive patients.
AB - BACKGROUND: Nonadherence to antihypertensive therapy is an important cause of
poor blood pressure control. However, to date, few effective and accurate tools
exist to routinely evaluate drug nonadherence. METHODS: In this observational
study, performed under conditions of routine clinical practice, we included 174
patients (aged 67 +/- 11 years) with treated essential hypertension who attended
the outpatient hypertension clinic of a university hospital. Adherence to
antihypertensive treatment was measured by using ultraperformance liquid
chromatography-tandem mass spectrometry in spot urine at the time of clinical
appointment and blood pressure measurement. Patients were also asked to report
their adherence using a validated questionnaire (four-item Morisky Medication
Adherence Scale). RESULTS: The prevalence of directly measured nonadherence by
urine drug detection was approximately 10%. Compared with adherent patients,
those who did not adhere to their treatment (n = 15) had a higher number of
antihypertensive pills and drugs (P = 0.02), cotreatment with cardiovascular
drugs (P < 0.05), and total concurrent medications and pills (P < 0.01). After
adjustment for age, SBP and DBP were higher in nonadherent than adherent group
(SBP: 146 +/- 18 vs. 131 +/- 14, respectively, P < 0.01; and DBP: 77 +/- 15 vs.
73 +/- 9, respectively, P < 0.01). There was no significant association between
four-item Morisky Medication Adherence Scale score and directly measured
nonadherence. A longitudinal analysis, performed in a subpopulation of 105
patients after a median follow-up of 11 months, showed that the adherence status
remained unchanged in 88% of patients. CONCLUSION: These results indicate a good
adherence to antihypertensive drugs in patients attending the outpatient clinics
of a university hospital. They suggest that urine detection of antihypertensive
drugs by ultraperformance liquid chromatography-tandem mass spectrometry is an
accurate and practical tool for directly monitoring adherence. This direct
information is not overlapping with self-report questionnaire.
PMID- 28505067
TI - Risk Assessment of Florists Exposed to Pesticide Residues through Handling of
Flowers and Preparing Bouquets.
AB - Flowers are frequently treated with pesticides and, as a result, florists
handling daily a large number of flowers can be exposed to pesticide residues. A
study was conducted among twenty volunteer florists located in Namur Province and
in the Brussels Capital Region of Belgium in order to assess their potential
dermal exposure to dislodgeable pesticide residues transferred from flowers to
hands. Two pairs of cotton gloves were worn during two consecutive half days
while handling flowers and preparing bouquets (from min 2 h to max 3 h/day). The
residual pesticide deposits on the glove samples were extracted with a multi
residue Quick Easy Cheap Effective Rugged Safe (QuEChERS) method and analyzed by
a combination of gas and liquid chromatography tandem mass spectrometry (GC-MS/MS
and LC-MS/MS) by an accredited laboratory. A total of 111 active substances
(mainly insecticides and fungicides) were detected, with an average of 37 active
substances per sample and a total concentration per glove sample of 22.22 mg/kg.
Several predictive levels of contamination were considered to assess the risk.
The potential dermal exposures (PDE) of florists were estimated at the average,
for different percentiles, and at the maximum concentration of residues in
samples. At the PDE P90 and at the PDEMAX (or worst case) values, three and five
active substances respectively exceed the Acceptable Operator Exposure Level
(AOEL), indicating risk situations. For the systemic exposure (SE), one active
substance (clofentezine) exceeds the AOEL at the P90 predictive level. In the
worst case, SEMAX (at the maximum concentrations), four active substances
(clofentezine, famoxadone, methiocarb, and pyridaben) exceed their respective
AOEL values. Among the 14 most frequently detected active substances, two have
SEMAX values exceeding the AOEL. Exposure could be particularly critical for
clofentezine with an SEMAX value four times higher than the AOEL (393%). The
exposure of florists appeared to be an example of a unique professional situation
in which workers are exposed regularly to both a very high number of toxic
chemicals and rather high concentration levels. Therefore the priority should be
to raise the level of awareness among the florists who must change their habits
and practices if they want to minimize their exposure.
PMID- 28505068
TI - A New Method for the Fast Analysis of Trihalomethanes in Tap and Recycled Waters
Using Headspace Gas Chromatography with Micro-Electron Capture Detection.
AB - Chemical disinfection of water supplies brings significant public health benefits
by reducing microbial contamination. The process can however, result in the
formation of toxic compounds through interactions between disinfectants and
organic material in the source water. These new compounds are termed disinfection
by-products (DBPs). The most common are the trihalomethanes (THMs) such as
trichloromethane (chloroform), dichlorobromomethane, chlorodibromomethane and
tribromomethane (bromoform); these are commonly reported as a single value for
total trihalomethanes (TTHMs). Analysis of DBPs is commonly performed via time-
and solvent-intensive sample preparation techniques such as liquid-liquid and
solid phase extraction. In this study, a method using headspace gas
chromatography with micro-electron capture detection was developed and applied
for the analysis of THMs in drinking and recycled waters from across Melbourne
(Victoria, Australia). The method allowed almost complete removal of the sample
preparation step whilst maintaining trace level detection limits (>1 ppb). All
drinking water samples had TTHM concentrations below the Australian regulatory
limit of 250 ug/L but some were above the U.S. EPA limit of 60 ug/L. The highest
TTHM concentration was 67.2 ug/L and lowest 22.9 ug/L. For recycled water,
samples taken directly from treatment plants held significantly higher
concentrations (153.2 ug/L TTHM) compared to samples from final use locations
(4.9-9.3 ug/L).
PMID- 28505070
TI - Characterization of Fine Metal Particles Derived from Shredded WEEE Using a
Hyperspectral Image System: Preliminary Results.
AB - Waste of electric and electronic equipment (WEEE) is the fastest-growing waste
stream in Europe. The large amount of electric and electronic products introduced
every year in the market makes WEEE disposal a relevant problem. On the other
hand, the high abundance of key metals included in WEEE has increased the
industrial interest in WEEE recycling. However, the high variability of materials
used to produce electric and electronic equipment makes key metals' recovery a
complex task: the separation process requires flexible systems, which are not
currently implemented in recycling plants. In this context, hyperspectral sensors
and imaging systems represent a suitable technology to improve WEEE recycling
rates and the quality of the output products. This work introduces the
preliminary tests using a hyperspectral system, integrated in an automatic WEEE
recycling pilot plant, for the characterization of mixtures of fine particles
derived from WEEE shredding. Several combinations of classification algorithms
and techniques for signal enhancement of reflectance spectra were implemented and
compared. The methodology introduced in this study has shown characterization
accuracies greater than 95%.
PMID- 28505069
TI - B-Vitamin Intake from Diet and Supplements and Breast Cancer Risk in Middle-Aged
Women: Results from the Prospective NutriNet-Sante Cohort.
AB - Experimental studies suggest a protective effect of B-vitamins on breast cancer
risk, potentially modulated by alcohol intake. However, epidemiological studies
are limited, especially regarding non-folate B-vitamins. Furthermore, few studies
included quantitative assessment of supplemental intake. This prospective study
aimed to investigate the associations between intakes of B-vitamins (dietary,
supplemental, total) and breast cancer risk. 27,853 women aged >=45 years from
the NutriNet-Sante cohort (2009-2016) were included, with a median follow-up time
of 4.2 years. Dietary data were collected using repeated 24 h records. A specific
questionnaire assessed dietary supplement use over a 12-month period. A
composition database of 8000 supplements was developed. Associations were
characterized by multivariable Cox models, and 462 incident breast cancers were
diagnosed. Dietary (HRQ4vs.Q1 = 0.74 (0.55, 0.99), P-trend = 0.05), supplemental
(HRQ4vs.Q1 = 0.61 (0.38, 0.98), P-trend = 0.05), and total (HRQ4vs.Q1 = 0.67
(0.50, 0.91), P-trend = 0.01) pyridoxine intakes were inversely associated with
breast cancer risk. Total thiamin intake was borderline inversely associated with
breast cancer risk (HRper 1-unit increment = 0.78 (0.61, 1.00), P = 0.05).
Statistically significant interactions between alcohol consumption and B-vitamin
(thiamin, riboflavin, niacin, pantothenic acid, pyridoxine, folate, and
cobalamin) supplemental intake were observed, the latter being inversely
associated with breast cancer risk in non-to-low alcohol drinkers but not in
higher drinkers. This large prospective study, including quantitative assessment
of supplemental intake, suggests a potential protective effect of pyridoxine and
thiamin on breast cancer risk in middle-aged women.
PMID- 28505072
TI - A Feasibility Study of Personalized Prescription Schemes for Glioblastoma
Patients Using a Proliferation and Invasion Glioma Model.
AB - Purpose: This study investigates the feasibility of personalizing radiotherapy
prescription schemes (treatment margins and fractional doses) for glioblastoma
(GBM) patients and their potential benefits using a proliferation and invasion
(PI) glioma model on phantoms. Methods and Materials: We propose a strategy to
personalize radiotherapy prescription schemes by simulating the proliferation and
invasion of the tumor in 2D according to the PI glioma model. We demonstrate the
strategy and its potential benefits by presenting virtual cases, where the
standard and personalized prescriptions were applied to the tumor. Standard
prescription was assumed to deliver 46 Gy in 23 fractions to the initial, gross
tumor volume (GTV1) plus a 2 cm margin and an additional 14 Gy in 7 fractions to
the boost GTV2 plus a 2 cm margin. The virtual cases include the tumors with a
moving velocity of 0.029 (slow-move), 0.079 (average-move), and 0.13 (fast-move)
mm/day for the gross tumor volume (GTV) with a radius of 1 (small) and 2 (large)
cm. For each tumor size and velocity, the margin around GTV1 and GTV2 was varied
between 0-6 cm and 1-3 cm, respectively. Equivalent uniform dose (EUD) to normal
brain was constrained to the EUD value obtained by using the standard
prescription. Various linear dose policies, where the fractional dose is linearly
decreasing, constant, or increasing, were investigated to estimate the temporal
effect of the radiation dose on tumor cell-kills. The goal was to find the
combination of margins for GTV1 and GTV2 and a linear dose policy, which minimize
the tumor cell-surviving fraction (SF) under a normal tissue constraint. The
efficacy of a personalized prescription was evaluated by tumor EUD and the
estimated survival time. Results: The personalized prescription for the slow-move
tumors was to use 3.0-3.5 cm margins for GTV1, and a 1.5 cm margin for GTV2. For
the average- and fast-move tumors, it was optimal to use a 6.0 cm margin for GTV1
and then 1.5-3.0 cm margins for GTV2, suggesting a course of whole brain therapy
followed by a boost to a smaller volume. It was more effective to deliver the
boost sequentially using a linearly decreasing fractional dose for all tumors.
Personalized prescriptions led to surviving fractions of 0.001-0.465% compared to
the standard prescription, and increased the tumor EUDs by 25.3-49.3% and
estimated survival times by 7.6-22.2 months. Conclusions: Personalizing treatment
margins based on the measured proliferative capacity of GBM tumor cells can
potentially lead to significant improvements in tumor cell kill and related
clinical outcomes.
PMID- 28505073
TI - Anti-Pigmentary Effect of (-)-4-Hydroxysattabacin from the Marine-Derived
Bacterium Bacillus sp.
AB - Bioactivity-guided isolation of a crude extract from a culture broth of Bacillus
sp. has led to the isolation of (-)-4-hydroxysattabacin (1). The inhibitory
effect of (-)-4-hydroxysattabacin (1) was investigated on melanogenesis in the
murine melanoma cell line, B16F10, and human melanoma cell line, MNT-1, as well
as a pigmented 3D-human skin model. (-)-4-Hydroxysattabacin treatment decreased
melanin contents in a dose-dependent manner in alpha-melanocyte stimulating
hormone (alpha-MSH)-stimulated B16F10 cells. Quantitative real time PCR (qRT-PCR)
demonstrated that treatment with (-)-4-hydroxysattabacin down-regulated several
melanogenic genes, including tyrosinase, tyrosinase-related protein 1 (TRP-1),
and tyrosinase-related protein 2 (TRP-2) while their enzymatic activities were
unaffected. The anti-melanogenic effects of (-)-4-hydroxysattabacin were further
demonstrated in a pigmented 3D human epidermal skin model, MelanodermTM, and
manifested as whitening and regression of melanocyte activation in the tissue.
PMID- 28505076
TI - Comprehensive and Highly Accurate Measurements of Crane Runways, Profiles and
Fastenings.
AB - The process of surveying crane runways has been continually refined due to the
competitive situation, modern surveying instruments, additional sensors,
accessories and evaluation procedures. Guidelines, such as the International
Organization for Standardization (ISO) 12488-1, define target values that must be
determined by survey. For a crane runway these are for example the span, the
position and height of the rails. The process has to be objective and
reproducible. However, common processes of surveying crane runways do not meet
these requirements sufficiently. The evaluation of the protocols, ideally by an
expert, requires many years of experience. Additionally, the recording of crucial
parameters, e.g., the wear of the rail, or the condition of the rail fastening
and rail joints, is not regulated and for that reason are often not considered
during the measurement. To solve this deficit the Advanced Rail Track Inspection
System (ARTIS) was developed. ARTIS is used to measure the 3D position of crane
rails, the cross-section of the crane rails, joints and, for the first time, the
(crane-rail) fastenings. The system consists of a monitoring vehicle and an
external tracking sensor. It makes kinematic observations with the tracking
sensor from outside the rail run, e.g., the floor of an overhead crane runway,
possible. In this paper we present stages of the development process of ARTIS,
new target values, calibration of sensors and results of a test measurement.
PMID- 28505071
TI - MYC-Master Regulator of the Cancer Epigenome and Transcriptome.
AB - Overexpression of MYC is a hallmark of many human cancers. The MYC oncogene has
long been thought to execute its neoplastic functions by acting as a classic
transcription factor, deregulating the expression of a large number of specific
target genes. However, MYC's influence on many of these target genes is rather
modest and there is little overlap between MYC regulated genes in different cell
types, leaving many mechanistic questions unanswered. Recent advances in the
field challenge the dogma further, revealing a role for MYC that extends beyond
the traditional concept of a sequence-specific transcription factor. In this
article, we review MYC's function as a regulator of the cancer epigenome and
transcriptome. We outline our current understanding of how MYC regulates
chromatin structure in both a site-specific and genome-wide fashion, and
highlight the implications for therapeutic strategies for cancers with high MYC
expression.
PMID- 28505075
TI - Knowledge about Iodine in Pregnant and Lactating Women in the Oslo Area, Norway.
AB - BACKGROUND: Lack of knowledge about iodine may be a risk factor for iodine
deficiency in pregnant and lactating women. The aim of this study was to assess
knowledge about iodine and predictors of iodine knowledge scores among pregnant
and lactating women. The study also examined whether iodine knowledge scores were
associated with iodine status. METHODS: A cross-sectional study was performed on
804 pregnant women and 175 lactating women from 18 to 44 years of age in 2016 in
the Oslo area, Norway. Knowledge about iodine was collected through a self
administered, paper-based questionnaire. Iodine concentrations in urine and
breast milk were measured using an inductively coupled plasma mass spectrometer
(ICPMS). RESULTS: 74% of the pregnant women and 55% of the lactating women
achieved none to low iodine knowledge scores. Higher educated pregnant women and
those who had received information about iodine had significantly higher
knowledge scores. In lactating women, increased age was associated with higher
knowledge scores. Knowledge scores were not associated with participants' iodine
status. CONCLUSION: This study revealed a lack of knowledge about the importance
of iodine in pregnant and lactating women, as well as about the most important
dietary sources. Public education initiatives are required to increase the
awareness about iodine in these population groups.
PMID- 28505074
TI - NAFLD and Atherosclerosis Are Prevented by a Natural Dietary Supplement
Containing Curcumin, Silymarin, Guggul, Chlorogenic Acid and Inulin in Mice Fed a
High-Fat Diet.
AB - Non-alcoholic fatty liver disease (NAFLD) confers an increased risk of
cardiovascular diseases. NAFDL is associated with atherogenic dyslipidemia,
inflammation and renin-angiotensin system (RAS) imbalance, which in turn lead to
atherosclerotic lesions. In the present study, the impact of a natural dietary
supplement (NDS) containing Curcuma longa, silymarin, guggul, chlorogenic acid
and inulin on NAFLD and atherosclerosis was evaluated, and the mechanism of
action was examined. C57BL/6 mice were fed an HFD for 16 weeks; half of the mice
were simultaneously treated with a daily oral administration (os) of the NDS.
NAFLD and atherogenic lesions in aorta and carotid artery (histological
analysis), hepatic expression of genes involved in the NAFLD (PCR array), hepatic
angiotensinogen (AGT) and AT1R mRNA expression (real-time PCR) and plasma
angiotensin (ANG)-II levels (ELISA) were evaluated. In the NDS group, steatosis,
aortic lesions or carotid artery thickening was not observed. PCR array showed
upregulation of some genes involved in lipid metabolism and anti-inflammatory
activity (Cpt2, Ifng) and downregulation of some genes involved in pro
inflammatory response and in free fatty acid up-take (Fabp5, Socs3). Hepatic AGT,
AT1R mRNA and ANG II plasma levels were significantly lower with respect to the
untreated-group. Furthermore, NDS inhibited the dyslipidemia observed in the
untreated animals. Altogether, these results suggest that NDS prevents NAFLD and
atherogenesis by modulating the expression of different genes involved in NAFLD
and avoiding RAS imbalance.
PMID- 28505078
TI - Intra-Minute Cloud Passing Forecasting Based on a Low Cost IoT Sensor-A Solution
for Smoothing the Output Power of PV Power Plants.
AB - Clouds moving at a high speed in front of the Sun can cause step changes in the
output power of photovoltaic (PV) power plants, which can lead to voltage
fluctuations and stability problems in the connected electricity networks. These
effects can be reduced effectively by proper short-term cloud passing forecasting
and suitable PV power plant output power control. This paper proposes a low-cost
Internet of Things (IoT)-based solution for intra-minute cloud passing
forecasting. The hardware consists of a Raspberry PI Model B 3 with a WiFi
connection and an OmniVision OV5647 sensor with a mounted wide-angle lens, a
circular polarizing (CPL) filter and a natural density (ND) filter. The
completely new algorithm for cloud passing forecasting uses the green and blue
colors in the photo to determine the position of the Sun, to recognize the
clouds, and to predict their movement. The image processing is performed in
several stages, considering selectively only a small part of the photo relevant
to the movement of the clouds in the vicinity of the Sun in the next minute. The
proposed algorithm is compact, fast and suitable for implementation on low cost
processors with low computation power. The speed of the cloud parts closest to
the Sun is used to predict when the clouds will cover the Sun. WiFi communication
is used to transmit this data to the PV power plant control system in order to
decrease the output power slowly and smoothly.
PMID- 28505079
TI - Melatonin Secretion Is Increased in Children with Severe Traumatic Brain Injury.
AB - BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and
disability in children. Oxidative stress plays a significant role in brain damage
and melatonin exhibits both direct and indirect antioxidant effects. The primary
aim of the present study was to evaluate serum melatonin levels in children with
severe TBI in comparison to critically ill children admitted to the Pediatric
Intensive Care Unit for conditions other than TBI. METHODS: Twenty-four children
were evaluated, equally divided into severe TBI and no-TBI. Blood samples for
serum melatonin analysis were collected at 22:00, 01:00, 03:00, 05:00, 08:00, and
12:00. RESULTS: Mean serum melatonin peaks in children of the TBI group were
higher compared to the values of no-TBI critically ill children (495 +/- 102 vs.
294 +/- 119 pg/mL, p = 0.0002). Furthermore, the difference was even more
significant in comparison to values reported in literature for healthy age
matched children (495 +/- 102 vs. 197 +/- 71 pg/mL, p < 0.0001). CONCLUSION: This
study has shown that endogenous serum melatonin levels dramatically increase in
children after severe TBI. This elevation is likely to represent a response to
oxidative stress and/or inflammation due to severe head injury.
PMID- 28505077
TI - Determination of Genes Related to Uveitis by Utilization of the Random Walk with
Restart Algorithm on a Protein-Protein Interaction Network.
AB - Uveitis, defined as inflammation of the uveal tract, may cause blindness in both
young and middle-aged people. Approximately 10-15% of blindness in the West is
caused by uveitis. Therefore, a comprehensive investigation to determine the
disease pathogenesis is urgent, as it will thus be possible to design effective
treatments. Identification of the disease genes that cause uveitis is an
important requirement to achieve this goal. To begin to answer this question, in
this study, a computational method was proposed to identify novel uveitis-related
genes. This method was executed on a large protein-protein interaction network
and employed a popular ranking algorithm, the Random Walk with Restart (RWR)
algorithm. To improve the utility of the method, a permutation test and a
procedure for selecting core genes were added, which helped to exclude false
discoveries and select the most important candidate genes. The five-fold cross
validation was adopted to evaluate the method, yielding the average F1-measure of
0.189. In addition, we compared our method with a classic GBA-based method to
further indicate its utility. Based on our method, 56 putative genes were chosen
for further assessment. We have determined that several of these genes (e.g.,
CCL4, Jun, and MMP9) are likely to be important for the pathogenesis of uveitis.
PMID- 28505081
TI - Isolation of Rice Bran Lectins and Characterization of Their Unique Behavior in
Caco-2 Cells.
AB - Rice bran lectins, named as RBA1 and RBA2, were isolated from Oryza sativa in two
chromatography steps: affinity chromatography and cation-exchange chromatography.
RBA1 was found to be composed of a covalently linked heterodimer of 20- and 12
kDa subunits, and RBA2 was a noncovalently linked dimer of 12-kDa subunits. Both
RBA1 and RBA2 bound to desialylated complex glycoproteins such as fetuin, alpha1
acid glycoprotein, and transferrin, and agalactosylated complex glycoproteins
such as agalacto fetuin, agalacto-alpha1-acid glycoprotein, and agalacto
transferrin, in addition to chitooligosacchrides. RBAs were heat stable up to 80
degrees C and stable at pH 4-10. RBA1 increased the transport of the fluorescent
marker, rhodamine 123, which is known to be transported via the P-glycoprotein
mediated efflux pathway across human intestinal Caco-2 cell monolayers.
Furthermore, RBA1 itself was transported to the basolateral side of the
monolayers via an endocytotic pathway.
PMID- 28505080
TI - First Insights into Human Fingertip Regeneration by Echo-Doppler Imaging and
Wound Microenvironment Assessment.
AB - Fingertip response to trauma represents a fascinating example of tissue
regeneration. Regeneration derives from proliferative mesenchymal cells
(blastema) that subsequently differentiate into soft and skeletal tissues.
Clinically, conservative treatment of the amputated fingertip under occlusive
dressing can shift the response to tissue loss from a wound repair process
towards regeneration. When analyzing by Immunoassay the wound exudate from
occlusive dressings, the concentrations of brain-derived neurotrophic factor
(BDNF) and leukemia inhibitory factor (LIF) were higher in fingertip exudates
than in burn wounds (used as controls for wound repair versus regeneration).
Vascular endothelial growth factor A (VEGF-A) and platelet-derived growth factor
(PDGF) were highly expressed in both samples in comparable levels. In our study,
pro-inflammatory cytokines were relatively higher expressed in regenerative
fingertips than in the burn wound exudates while chemokines were present in lower
levels. Functional, vascular and mechanical properties of the regenerated
fingertips were analyzed three months after trauma and the data were compared to
the corresponding fingertip on the collateral uninjured side. While sensory
recovery and morphology (pulp thickness and texture) were similar to uninjured
sides, mechanical parameters (elasticity, vascularization) were increased in the
regenerated fingertips. Further studies should be done to clarify the importance
of inflammatory cells, immunity and growth factors in determining the outcome of
the regenerative process and its influence on the clinical outcome.
PMID- 28505082
TI - Supervised Clustering of Adipokines and Hormonal Receptors Predict Prognosis in a
Population of Obese Women with Type 1 Endometrial Cancer.
AB - Obesity is a major risk factor for endometrial cancer (EC). Yet, its impact on
prognosis is controversial. Obesity is associated with metabolic and hormonal
dysregulation as well as adipokines increase. The aim of this study was to
characterize the expression of biological factors related to obesity within the
tumor and evaluate their impact on prognosis. One hundred and thirty-six
patients, including 55 obese patients, with endometrioid type I EC operated by
total hysterectomy were included in this retrospective study conducted in a
Tertiary teaching hospital between 2000 and 2013. Immunohistochemistry (IHC)
study was performed on type I EC tumor samples using five adipokines (SPARC, RBP4
(Retinol Binding Protein 4), adiponectin, TNF alpha, IL-6) and hormonal receptors
(estrogen receptor and progesterone receptor). Supervised clustering of
immunohistochemical markers was performed to identify clusters that could be
associated with prognostic groups. The prognosis of the obese population was not
different from the prognosis of the general population. Adipokine expression
within tumors was not different in these two populations. In obese population, we
found three clusters where co-expression was associated with a recurrence group
in comparison with a non-recurrence group and four clusters where co-expression
was associated with the high risk FIGO (International Federation of Gynecology
and Obstetrics) stage I group in comparison of low risk FIGO stage I group. While
obesity does not appear as a prognostic factor in endometrioid type I EC, the co
expression of biological factors in IHC on hysterectomy specimens allowed to
distinguish two prognostic groups in obese population.
PMID- 28505083
TI - Family Planning and the Samburu: A Qualitative Study Exploring the Thoughts of
Men on a Population Health and Environment Programme in Rural Kenya.
AB - Population Health and Environment (PHE) strategies are argued to improve
ecosystem and human health by addressing family size and its effects on natural
resource use, food security, and reproductive health. This study investigates
men's views on a PHE family planning (FP) programme delivered among the pastoral
Samburu tribe in rural northern Kenya. Three focus group discussions and nine
semi-structured interviews were conducted with 27 Samburu men. These discussions
revealed support for environmentally-sensitised family planning promotion. Men
highlighted their dependency on natural resources and challenges faced in
providing for large families and maintaining livestock during drought. These
practices were said to lead to natural resource exhaustion, environmental
degradation, and wildlife dispersal, undermining key economic benefits of
environmental and wildlife conservation. Relating family size to the environment
is a compelling strategy to improve support for FP among Samburu men. Kenyan
policy-makers should consider integrating community-based PHE strategies among
underserved pastoral groups living in fragile ecosystems.
PMID- 28505085
TI - Sparsity Adaptive Matching Pursuit Detection Algorithm Based on Compressed
Sensing for Radar Signals.
AB - In this paper, the application of the emerging compressed sensing (CS) theory and
the geometric characteristics of the targets in radar images are investigated.
Currently, the signal detection algorithms based on the CS theory require knowing
the prior knowledge of the sparsity of target signals. However, in practice, it
is often impossible to know the sparsity in advance. To solve this problem, a
novel sparsity adaptive matching pursuit (SAMP) detection algorithm is proposed.
This algorithm executes the detection task by updating the support set and
gradually increasing the sparsity to approximate the original signal. To verify
the effectiveness of the proposed algorithm, the data collected in 2010 at
Pingtan, which located on the coast of the East China Sea, were applied.
Experiment results illustrate that the proposed method adaptively completes the
detection task without knowing the signal sparsity, and the similar detection
performance is close to the matching pursuit (MP) and orthogonal matching pursuit
(OMP) detection algorithms.
PMID- 28505084
TI - Food Sources of Energy and Nutrients in Infants, Toddlers, and Young Children
from the Mexican National Health and Nutrition Survey 2012.
AB - Food sources of nutrients in Mexican children are not well known. To fill the
knowledge gap, dietary intake was assessed in 2057 children using a 24-hour
dietary recall. All reported foods and beverages were assigned to one of 76 food
groups. Percent contribution of each food group to nutrient intake was estimated
for four age groups: 0-5.9, 6-11.9, 12-23.9, and 24-47.9 months. Breast milk,
infant formula, and cow's milk were the top sources of energy and nutrients,
especially in younger groups. Among infants aged 6-11.9 months, the top food
sources of energy included soups and stews, cookies, fruit, tortillas, eggs and
egg dishes, and traditional beverages. The same foods plus sweetened breads,
dried beans, and sandwiches and tortas were consumed as the top sources of energy
among toddlers and young children. Milk, soups, and stews were the top
contributors for all nutrients and tortillas, eggs, and egg dishes were among the
top contributors for iron and zinc. This study showed that low nutrient-dense
cookies, sweetened breads, and traditional beverages were among the core foods
consumed early in life in Mexico. This compromises the intake of more nutritious
foods such as vegetables and fortified cereals and increases the risk of obesity.
PMID- 28505086
TI - Raspberry-Like Bismuth Oxychloride on Mesoporous Siliceous Support for Sensitive
Electrochemical Stripping Analysis of Cadmium.
AB - BiOCl-SiO2 KIT-6 composite materials with raspberry-like structures are facilely
prepared under hydrothermal conditions. The mesoporous siliceous support of SiO2
KIT-6-incorporated BiOCl with enlarged yet refined surface morphology
characterized by physiochemical methods exhibits an improved electrochemical
performance. A sensitive electrochemical detection method of cadmium
concentration using square wave anodic stripping voltammetry was developed based
on BiOCl-SiO2 KIT-6 composite-modified glassy carbon electrodes, which displayed
wide linear ranges of 0.5 to 10 MUg/L and 10 to 300 MUg/L and a detection limit
of 65 ng/L. The sensitive, versatile and eco-friendly sensor was successfully
applied for the determination of cadmium-spiked human blood samples.
PMID- 28505088
TI - 1,4-Naphthoquinone Triggers Nematode Lethality by Inducing Oxidative Stress and
Activating Insulin/IGF Signaling Pathway in Caenorhabditis elegans.
AB - Plant-parasitic nematodes are destructive pathogens causing enormous economic
losses worldwide. With the withdrawal of fumigants, organophosphates and
carbamates, pathogenic nematode control is more difficult. Phytochemicals are the
plant secondary metabolites and are friendly for men and the environment. For
developing new nematocidal candidates, we screened 790 phytochemicals using the
model organism Caenorhabditis elegans and found 10 active compounds, 3 of which
were further evaluated for their inhibitory activities against egg hatching of C.
elegans and J2 Meloidogyne incognita. Among them, 1,4-naphthoquinone (1,4-NQ) was
the only compound that could kill more than 50% of targets at 50 MUg/mL,
prompting us to investigate how 1,4-NQ triggers nematode lethality. In C.
elegans, we observed that 1,4-NQ could influence reactive oxygen production,
superoxide dismutase activity, and the heat-shock transcription factor (HSF)-1
pathway, which indicated that 1,4-NQ stimulated significant oxidative stress.
Furthermore, using quantitative RT-PCR and transgenetic nematodes, we revealed
that 1,4-NQ lethality was related to the Insulin/IGF signaling (IIS) pathway, and
the effect of 1,4-NQ on IIS pathway related genes indicated that 1,4-NQ could
activate this pathway and suppress the expression of DAF-16 target genes. The
triggering of oxidative stress and activation of the IIS pathway indicated that
1,4-NQ operates through the generation of oxygen radicals, which can be lethal to
C. elegans, thus making it an interesting lead compound for the development of
future nematocides.
PMID- 28505089
TI - Squeeze-Film Air Damping of a Five-Axis Electrostatic Bearing for Rotary
Micromotors.
AB - Air-film damping, which dominates over other losses, plays a significant role in
the dynamic response of many micro-fabricated devices with a movable mass
suspended by various bearing mechanisms. Modeling the damping characteristics
accurately will be greatly helpful to the bearing design, control, and test in
various micromotor devices. This paper presents the simulated and experimental
squeeze-film air damping results of an electrostatic bearing for use in a rotary
high-speed micromotor. It is shown that the boundary condition to solve the three
dimensional Reynolds equation, which governs the squeeze-film damping in the air
gap between the rotor and its surrounding stator sealed in a three-layer
evacuated cavity, behaves with strong cross-axis coupling characteristics. To
accurately characterize the damping effect, a set of multiphysics finite-element
simulations are performed by computing both the rotor velocity and the
distribution of the viscous damping force acting on the rotor. The damping
characteristics varying with several key structure parameters are simulated and
discussed to optimize the device structure for desirable rotor dynamics. An
electrical measurement method is also proposed and applied to validate the
numerical results of the damping coefficients experimentally. Given that the
frequency response of the electric bearing is critically dependent on the damping
coefficients at atmospheric pressure, a solution to the air-film damping
measurement problem is presented by taking approximate curve fitting of multi
axis experimental frequency responses. The measured squeeze-film damping
coefficients for the five-axis electric bearing agrees well with the numerical
solutions. This indicates that numerical multiphysics simulation is an effective
method to accurately examine the air-film damping effect for complex device
geometry and arbitrary boundary condition. The accurate damping coefficients
obtained by FEM simulation will greatly simplify the design of the five-axis
bearing control system and facilitate the initial suspension test of the rotor
for various micromotor devices.
PMID- 28505087
TI - The Effect of Diet on the Survival of Patients with Chronic Kidney Disease.
AB - The prevalence of chronic kidney disease (CKD) is high and it is gradually
increasing. Individuals with CKD should introduce appropriate measures to hamper
the progression of kidney function deterioration as well as prevent the
development or progression of CKD-related diseases. A kidney-friendly diet may
help to protect kidneys from further damage. Patients with kidney damage should
limit the intake of certain foods to reduce the accumulation of unexcreted
metabolic products and also to protect against hypertension, proteinuria and
other heart and bone health problems. Despite the fact that the influence of
certain types of nutrients has been widely studied in relation to kidney function
and overall health in CKD patients, there are few studies on the impact of a
specific diet on their survival. Animal studies demonstrated prolonged survival
of rats with CKD fed with protein-restricted diets. In humans, the results of
studies are conflicting. Some of them indicate slowing down of the progression of
kidney disease and reduction in proteinuria, but other underline significant
worsening of patients' nutritional state, which can be dangerous. A recent
systemic study revealed that a healthy diet comprising many fruits and
vegetables, fish, legumes, whole grains, and fibers and also the cutting down on
red meat, sodium, and refined sugar intake was associated with lower mortality in
people with kidney disease. The aim of this paper is to review the results of
studies concerning the impact of diet on the survival of CKD patients.
PMID- 28505090
TI - Evaluation of Ochratoxin Recognition by Peptides Using Explicit Solvent Molecular
Dynamics.
AB - Biosensing platforms based on peptide recognition provide a cost-effective and
stable alternative to antibody-based capture and discrimination of ochratoxin-A
(OTA) vs. ochratoxin-B (OTB) in monitoring bioassays. Attempts to engineer
peptides with improved recognition efficacy require thorough structural and
thermodynamic characterization of the binding-competent conformations. Classical
molecular dynamics (MD) approaches alone do not provide a thorough assessment of
a peptide's recognition efficacy. In this study, in-solution binding properties
of four different peptides, a hexamer (SNLHPK), an octamer (CSIVEDGK), NFO4
(VYMNRKYYKCCK), and a 13-mer (GPAGIDGPAGIRC), which were previously generated for
OTA-specific recognition, were evaluated using an advanced MD simulation approach
involving accelerated configurational search and predictive modeling. Peptide
configurations relevant to ochratoxin binding were initially generated using
biased exchange metadynamics and the dynamic properties associated with the in
solution peptide-ochratoxin binding were derived from Markov State Models. Among
the various peptides, NFO4 shows superior in-solution OTA sensing and also shows
superior selectivity for OTA vs. OTB due to the lower penalty associated with
solvating its bound complex. Advanced MD approaches provide structural and
energetic insights critical to the hapten-specific recognition to aid the
engineering of peptides with better sensing efficacies.
PMID- 28505092
TI - Molecular Characterization and Expression Profiling of Tomato GRF Transcription
Factor Family Genes in Response to Abiotic Stresses and Phytohormones.
AB - Growth regulating factors (GRFs) are plant-specific transcription factors that
are involved in diverse biological and physiological processes, such as growth,
development and stress and hormone responses. However, the roles of GRFs in
vegetative and reproductive growth, development and stress responses in tomato
(Solanum lycopersicum) have not been extensively explored. In this study, we
characterized the 13 SlGRF genes. In silico analysis of protein motif
organization, intron-exon distribution, and phylogenetic classification confirmed
the presence of GRF proteins in tomato. The tissue-specific expression analysis
revealed that most of the SlGRF genes were preferentially expressed in young and
growing tissues such as flower buds and meristems, suggesting that SlGRFs are
important during growth and development of these tissues. Some of the SlGRF genes
were preferentially expressed in fruits at distinct developmental stages
suggesting their involvement in fruit development and the ripening process. The
strong and differential expression of different SlGRFs under NaCl, drought, heat,
cold, abscisic acid (ABA), and jasmonic acid (JA) treatment, predict possible
functions for these genes in stress responses in addition to their growth
regulatory functions. Further, differential expression of SlGRF genes upon
gibberellic acid (GA3) treatment indicates their probable function in flower
development and stress responses through a gibberellic acid (GA)-mediated
pathway. The results of this study provide a basis for further functional
analysis and characterization of this important gene family in tomato.
PMID- 28505095
TI - Behavioural Profiles of Brown and Sloth Bears in Captivity.
AB - Three brown bear (Ursusarctosarctos) individuals and two sloth bear
(Melursusursinusinornatus) individuals were observed in captivity to produce
behavioural profiles for each individual. Data collected through behavioural
observations were used to produce activity budgets, and to identify space usage
and certain aspects of social behavior. Behaviour monitoring allowed the
researchers to evaluate the welfare of the animals by identifying the occurrence
of stereotypic behaviours, which are sometimes associated with stress.
Behavioural profiles were created using data obtained through behavioural
observations (coding) and keeper questionnaires (rating). The behavioural
observations indicated a number of stereotypic behaviours in sloth bears but not
in brown bears. The uniformity of zone usage was calculated to investigate if the
enclosure size and features were adequate for use, and a social aspect of
otherwise solitary animals was also identified. The behavioural profiles
generated through coding and rating were compared to determine the reliability
between these two methods in Ursids. Profiles were not compared between
individuals since this study is not a comparison between different personality
types but rather an effort (one of the few ones existing in literature) to select
a valid and reproducible methodology capable of assessing personality in bears.
PMID- 28505094
TI - Antigiardial Activity of Podophyllotoxin-Type Lignans from Bursera fagaroides
var. fagaroides.
AB - Giardiasis, a diarrheal disease, is highly prevalent in developing countries.
Several drugs are available for the treatment of this parasitosis; unfortunately,
all of them have variable efficacies and adverse effects. Bursera fagaroides has
been known for its anti-inflammatory and antidiarrheal properties in Mexican
traditional medicine. We investigated the in vitro anti-giardial activities of
four podophyllotoxin-type lignans from Bursera fagaroides var. fagaroides,
namely, 5'-desmethoxy-beta-peltatin-A-methylether (5-DES), acetylpodophyllotoxin
(APOD), burseranin (BUR), and podophyllotoxin (POD). All lignans affected the
Giardia adhesion and electron microscopy images revealed morphological
alterations in the caudal region, ventral disk, membrane, and flagella, to
different extents. Only 5-DES, APOD, and POD caused growth inhibition. Using the
Caco-2 human cell line as a model of the intestinal epithelium, we demonstrated
that APOD displayed direct antigiardial killing activity and low toxicity on Caco
2 cells. This finding makes it an attractive potential starting point for new
antigiardial drugs.
PMID- 28505091
TI - The Importance of NADPH Oxidases and Redox Signaling in Angiogenesis.
AB - Eukaryotic cells have to cope with the constant generation of reactive oxygen
species (ROS). Although the excessive production of ROS might be deleterious for
cell biology, there is a plethora of evidence showing that moderate levels of ROS
are important for the control of cell signaling and gene expression. The family
of the nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidases or
Nox) has evolved to produce ROS in response to different signals; therefore, they
fulfil a central role in the control of redox signaling. The role of NADPH
oxidases in vascular physiology has been a field of intense study over the last
two decades. In this review we will briefly analyze how ROS can regulate
signaling and gene expression. We will address the implication of NADPH oxidases
and redox signaling in angiogenesis, and finally, the therapeutic possibilities
derived from this knowledge will be discussed.
PMID- 28505093
TI - The Crucial Role of DNA Methylation and MeCP2 in Neuronal Function.
AB - A neuron is unique in its ability to dynamically modify its transcriptional
output in response to synaptic activity while maintaining a core gene expression
program that preserves cellular identity throughout a lifetime that is longer
than almost every other cell type in the body. A contributing factor to the
immense adaptability of a neuron is its unique epigenetic landscape that elicits
locus-specific alterations in chromatin architecture, which in turn influences
gene expression. One such epigenetic modification that is sensitive to changes in
synaptic activity, as well as essential for maintaining cellular identity, is DNA
methylation. The focus of this article is on the importance of DNA methylation in
neuronal function, summarizing recent studies on critical players in the
establishment of (the "writing"), the modification or erasure of (the "editing"),
and the mediation of (the "reading") DNA methylation in neurodevelopment and
neuroplasticity. One "reader" of DNA methylation in particular, methyl-CpG
binding protein 2 (MeCP2), is highlighted, given its undisputed importance in
neuronal function.
PMID- 28505097
TI - Nonlinear Parameter Identification of a Resonant Electrostatic MEMS Actuator.
AB - We experimentally investigate the primary superharmonic of order two and
subharmonic of order one-half resonances of an electrostatic MEMS actuator under
direct excitation. We identify the parameters of a one degree of freedom (1-DOF)
generalized Duffing oscillator model representing it. The experiments were
conducted in soft vacuum to reduce squeeze-film damping, and the actuator
response was measured optically using a laser vibrometer. The predictions of the
identified model were found to be in close agreement with the experimental
results. We also identified the noise spectral density of process (actuation
voltage) and measurement noise.
PMID- 28505096
TI - Attenuation of Drought Stress in Brassica Seedlings with Exogenous Application of
Ca2+ and H2O2.
AB - Drought is one of the most common abiotic stresses, affecting the growth and
productivity of crop plants globally, particularly in arid and semi-arid regions.
Different strategies are used to mitigate the impact of drought among crop
plants. Exogenous application of different substances are known to decrease the
effects of various abiotic stresses, including drought stress. The aim of this
study was to evaluate the effect of Ca2+ and H2O2 in developing drought stress
tolerance in Brassica napus "Bulbul-98" seedlings. Brassica napus "Bulbul-98"
seedlings were exposed to 5, 10 and 15 mM Ca2+ and 2, 5 and 10 MUM H2O2
concentrations twice at an interval of two days for up to 20 days after
germination. Drought stress decreased relative water content (RWC), chlorophyll
content and increased proline, H2O2, soluble protein and electrolyte leakage in
Brassica seedlings. Exogenous Ca2+ (5, 10,15 mM) and H2O2 (2, 5, 10 MUM)
supplementations, during drought stress induction, showed a significant increase
in RWC by 5.4%, 18.06%, 26.2% and 6.87%, 13.9%, 18.3% respectively. Similarly,
with the exogenous application of Ca2+ (5, 10, 15 mM) and H2O2 (2, 5, 10 MUM),
chlorophyll content was increased by 15.03%, 22.2%, and 28.4%, and 9.6%, 23.3%,
and 27.5% respectively. It was confirmed that the seedlings under drought stress
that were supplemented with Ca2+ and H2O2 recovered from water content reduction
and chlorosis, and were able to grow normally.
PMID- 28505098
TI - Alcohols as Substrates and Solvents for the Construction of 3-Alkoxylated-2
Oxindoles by Direct Alkoxylation of 3-Halooxindoles.
AB - Described herein is an environmentally benign method for the synthesis of
multisubstituted 3-alkoxylated-2-oxindoles 3 via direct alkoxylation of 3
halooxindoles 1. A wide variety of such multisubstituted 3-alkoxylated-2-oxindole
scaffolds were smoothly obtained in good yields (up to 94%) by heating in an oil
bath at 35 degrees C for 24 h. A particularly valuable feature of this method
was the development of environment-friendly chemistry using alcohols 2 as both
the substrates and solvents in the presence of a catalytic amount of base.
PMID- 28505099
TI - Mutational and Kinetic Analysis of Lesion Recognition by Escherichia coli
Endonuclease VIII.
AB - Escherichia coli endonuclease VIII (Endo VIII) is a DNA glycosylase with
substrate specificity for a wide range of oxidatively damaged pyrimidine bases.
Endo VIII catalyzes hydrolysis of the N-glycosidic bond and beta, delta
elimination of 3'- and 5'-phosphate groups of an apurinic/apyrimidinic site.
Single mutants of Endo VIII L70S, L70W, Y71W, F121W, F230W, and P253W were
analyzed here with the aim to elucidate the kinetic mechanism of protein
conformational adjustment during damaged-nucleotide recognition and catalytic
complex formation. F121W substitution leads to a slight reduction of DNA binding
and catalytic activity. F230W substitution slows the rate of the delta
elimination reaction indicating that interaction of Phe230 with a 5'-phosphate
group proceeds in the latest catalytic step. P253W Endo VIII has the same
activity as the wild type (WT) enzyme. Y71W substitution slightly reduces the
catalytic activity due to the effect on the later steps of catalytic-complex
formation. Both L70S and L70W substitutions significantly decrease the catalytic
activity, indicating that Leu70 plays an important role in the course of enzyme
DNA catalytic complex formation. Our data suggest that Leu70 forms contacts with
DNA earlier than Tyr71 does. Therefore, most likely, Leu70 plays the role of a
DNA lesion "sensor", which is used by Endo VIII for recognition of a DNA damage
site.
PMID- 28505100
TI - Preclinical Evaluation of the Efficacy of Antivenoms for Snakebite Envenoming:
State-of-the-Art and Challenges Ahead.
AB - Animal-derived antivenoms constitute the mainstay in the therapy of snakebite
envenoming. The efficacy of antivenoms to neutralize toxicity of medically
relevant snake venoms has to be demonstrated through meticulous preclinical
testing before their introduction into the clinical setting. The gold standard in
the preclinical assessment and quality control of antivenoms is the
neutralization of venom-induced lethality. In addition, depending on the
pathophysiological profile of snake venoms, the neutralization of other toxic
activities has to be evaluated, such as hemorrhagic, myotoxic, edema-forming,
dermonecrotic, in vitro coagulant, and defibrinogenating effects. There is a need
to develop laboratory assays to evaluate neutralization of other relevant venom
activities. The concept of the 3Rs (Replacement, Reduction, and Refinement) in
Toxinology is of utmost importance, and some advances have been performed in
their implementation. A significant leap forward in the study of the
immunological reactivity of antivenoms against venoms has been the development of
"antivenomics", which brings the analytical power of mass spectrometry to the
evaluation of antivenoms. International partnerships are required to assess the
preclinical efficacy of antivenoms against snake venoms in different regions of
the world in order to have a detailed knowledge on the neutralizing profile of
these immunotherapeutics.
PMID- 28505103
TI - Neuronal Migration and AUTS2 Syndrome.
AB - Neuronal migration is one of the pivotal steps to form a functional brain, and
disorganization of this process is believed to underlie the pathology of
psychiatric disorders including schizophrenia, autism spectrum disorders (ASD)
and epilepsy. However, it is not clear how abnormal neuronal migration causes
mental dysfunction. Recently, a key gene for various psychiatric diseases, the
Autism susceptibility candidate 2 (AUTS2), has been shown to regulate neuronal
migration, which gives new insight into understanding this question.
Interestingly, the AUTS2 protein has dual functions: Cytoplasmic AUTS2 regulates
actin cytoskeleton to control neuronal migration and neurite extension, while
nuclear AUTS2 controls transcription of various genes as a component of the
polycomb complex 1 (PRC1). In this review, we discuss AUTS2 from the viewpoint of
human genetics, molecular function, brain development, and behavior in animal
models, focusing on its role in neuronal migration.
PMID- 28505101
TI - Dairy Propionibacteria: Versatile Probiotics.
AB - Dairy propionibacteria are used as cheese ripening starters, as biopreservative
and as beneficial additives, in the food industry. The main species,
Propionibacterium freudenreichii, is known as GRAS (Generally Recognized As Safe,
USA, FDA). In addition to another dairy species, Propionibacterium
acidipropionici, they are included in QPS (Qualified Presumption of Safety) list.
Additional to their well-known technological application, dairy propionibacteria
increasingly attract attention for their promising probiotic properties. The
purpose of this review is to summarize the probiotic characteristics of dairy
propionibacteria reported by the updated literature. Indeed, they meet the
selection criteria for probiotic bacteria, such as the ability to endure
digestive stressing conditions and to adhere to intestinal epithelial cells. This
is a prerequisite to bacterial persistence within the gut. The reported
beneficial effects are ranked according to property's type: microbiota
modulation, immunomodulation, and cancer modulation. The proposed molecular
mechanisms are discussed. Dairy propionibacteria are described as producers of
nutraceuticals and beneficial metabolites that are responsible for their
versatile probiotic attributes include short chain fatty acids (SCFAs),
conjugated fatty acids, surface proteins, and 1,4-dihydroxy-2-naphtoic acid
(DHNA). These metabolites possess beneficial properties and their production
depends on the strain and on the growth medium. The choice of the fermented food
matrix may thus determine the probiotic properties of the ingested product. This
review approaches dairy propionibacteria, with an interest in both technological
abilities and probiotic attributes.
PMID- 28505102
TI - Bone-Protective Effects of Dried Plum in Postmenopausal Women: Efficacy and
Possible Mechanisms.
AB - Osteoporosis is an age-related chronic disease characterized by a loss of bone
mass and quality, and is associated with an increased risk of fragility
fractures. Postmenopausal women are at the greatest risk of developing
osteoporosis due to the cessation in ovarian hormone production, which causes
accelerated bone loss. As the demographic shifts to a more aged population, a
growing number of postmenopausal women will be afflicted with osteoporosis.
Certain lifestyle factors, including nutrition and exercise, are known to reduce
the risk of developing osteoporosis and therefore play an important role in bone
health. In terms of nutrition, accumulating evidence suggests that dried plum
(Prunus domestica L.) is potentially an efficacious intervention for preventing
and reversing bone mass and structural loss in an ovariectomized rat model of
osteoporosis, as well as in osteopenic postmenopausal women. Here, we provide
evidence supporting the efficacy of dried plum in preventing and reversing bone
loss associated with ovarian hormone deficiency in rodent models and in humans.
We end with the results of a recent follow-up study demonstrating that
postmenopausal women who previously consumed 100 g dried plum per day during our
one-year clinical trial conducted five years earlier retained bone mineral
density to a greater extent than those receiving a comparative control.
Additionally, we highlight the possible mechanisms of action by which bioactive
compounds in dried plum exert bone-protective effects. Overall, the findings of
our studies and others strongly suggest that dried plum in its whole form is a
promising and efficacious functional food therapy for preventing bone loss in
postmenopausal women, with the potential for long-lasting bone-protective
effects.
PMID- 28505104
TI - Identification and Validation of SAA4 as a Rheumatoid Arthritis Prescreening
Marker by Liquid Chromatography Tandem-mass Spectrometry.
AB - Rheumatoid arthritis (RA) is a chronic autoimmune disease that progresses into
systemic inflammation and joint deformity. RA diagnosis is a complicated
procedure, and early diagnostic methods are insufficient. Therefore, in this
study, we attempted to identify new markers to improve the accuracy of RA
prescreening. e identified differentially expressed proteins (DEPs) by using
liquid chromatography tandem-mass spectrometry in health-prescreening sera with
high rheumatoid factor (RF) values, and compared the findings with those from
sera with normal RF values. We identified 93 DEPs; of these, 36 were upregulated,
and 57 were downregulated in high-RF sera. Pathway analysis revealed that these
DEPs were related to immune responses. Additionally, four DEPs were statistically
analyzed by proteomic analysis; of these, SAA4 was significantly validated in
individual enzyme-linked immunosorbent assays. Moreover, SAA4 was significantly
upregulated in RA patients (n = 40, 66.43 +/- 12.97 ng/mL) compared with normal
controls (n = 40, 4.79 +/- 0.95 ng/mL) and had a higher area under the curve than
C-reactive protein. Thus, we identified SAA4 as a protein that was positively
correlated with RF and RA. SAA4 may represent a novel prescreening marker for the
diagnosis of RA.
PMID- 28505106
TI - Human Chorionic Gonadotropin: The Pregnancy Hormone and More.
AB - To thoroughly review the uses of human chorionic gonadotropin (hCG) related to
the process of reproduction and also assess new, non-traditional theories. Review
of the international literature and research studies. hCG and its receptor,
LH/CGR, are expressed in numerous sites of the reproductive tract, both in
gonadal and extra-goanadal tissues, promoting oocyte maturation, fertilization,
implantation and early embryo development. Moreover, hCG seems to have a
potential role as an anti-rejection agent in solid organ transplantation. Future
research needs to focus extensively on the functions of hCG and its receptor
LH/CGR, in an effort to reveal known, as well as unknown clinical potentials.
PMID- 28505105
TI - New Functions of APC/C Ubiquitin Ligase in the Nervous System and Its Role in
Alzheimer's Disease.
AB - The E3 ubiquitin ligase Anaphase Promoting Complex/Cyclosome (APC/C) regulates
important processes in cells, such as the cell cycle, by targeting a set of
substrates for degradation. In the last decade, APC/C has been related to several
major functions in the nervous system, including axon guidance, synaptic
plasticity, neurogenesis, and neuronal survival. Interestingly, some of the
identified APC/C substrates have been related to neurodegenerative diseases.
There is an accumulation of some degradation targets of APC/C in Alzheimer's
disease (AD) brains, which suggests a dysregulation of the protein complex in the
disorder. Moreover, recently evidence has been provided for an inactivation of
APC/C in AD. It has been shown that oligomers of the AD-related peptide, Abeta,
induce degradation of the APC/C activator subunit cdh1, in vitro in neurons in
culture and in vivo in the mouse hippocampus. Furthermore, in the AD mouse model
APP/PS1, lower cdh1 levels were observed in pyramidal neurons in CA1 when
compared to age-matched wildtype mice. In this review, we provide a complete list
of APC/C substrates that are involved in the nervous system and we discuss their
functions. We also summarize recent studies that show neurobiological effects in
cdh1 knockout mouse models. Finally, we discuss the role of APC/C in the
pathophysiology of AD.
PMID- 28505107
TI - Raman Spectroscopy of Head and Neck Cancer: Separation of Malignant and Healthy
Tissue Using Signatures Outside the "Fingerprint" Region.
AB - The ability to rapidly and accurately discriminate between healthy and malignant
tissue offers surgeons a tool for in vivo analysis that would potentially reduce
operating time, facilitate quicker recovery, and improve patient outcomes. To
this end, we investigate discrimination between diseased tissue and adjacent
healthy controls from patients with head and neck cancer using near-infrared
Raman spectroscopy. Our results indicate previously unreported peaks in the Raman
spectra that lie outside the conventional "fingerprint" region (400 cm-1-1800 cm
1) played an important role in our analysis and in discriminating between the
tissue classes. Preliminary multivariate statistical analyses of the Raman
spectra indicate that discrimination between diseased and healthy tissue is
possible based on these peaks.
PMID- 28505108
TI - Measurement of Vibrations in Two Tower-Typed Assistant Personal Robot
Implementations with and without a Passive Suspension System.
AB - This paper presents the vibration pattern measurement of two tower-typed
holonomic mobile robot prototypes: one based on a rigid mechanical structure, and
the other including a passive suspension system. Specific to the tower-typed
mobile robots is that the vibrations that originate in the lower part of the
structure are transmitted and amplified to the higher areas of the tower, causing
an unpleasant visual effect and mechanical stress. This paper assesses the use of
a suspension system aimed at minimizing the generation and propagation of
vibrations in the upper part of the tower-typed holonomic robots. The two robots
analyzed were equipped with onboard accelerometers to register the acceleration
over the X, Y, and Z axes in different locations and at different velocities. In
all the experiments, the amplitude of the vibrations showed a typical Gaussian
pattern which has been modeled with the value of the standard deviation. The
results have shown that the measured vibrations in the head of the mobile robots,
including a passive suspension system, were reduced by a factor of 16.
PMID- 28505109
TI - The Vip3Ag4 Insecticidal Protoxin from Bacillus thuringiensis Adopts A Tetrameric
Configuration That Is Maintained on Proteolysis.
AB - The Vip3 proteins produced during vegetative growth by strains of the bacterium
Bacillus thuringiensis show insecticidal activity against lepidopteran insects
with a mechanism of action that may involve pore formation and apoptosis. These
proteins are promising supplements to our arsenal of insecticidal proteins, but
the molecular details of their activity are not understood. As a first step in
the structural characterisation of these proteins, we have analysed their
secondary structure and resolved the surface topology of a tetrameric complex of
the Vip3Ag4 protein by transmission electron microscopy. Sites sensitive to
proteolysis by trypsin are identified and the trypsin-cleaved protein appears to
retain a similar structure as an octomeric complex comprising four copies each of
the ~65 kDa and ~21 kDa products of proteolysis. This processed form of the toxin
may represent the active toxin. The quality and monodispersity of the protein
produced in this study make Vip3Ag4 a candidate for more detailed structural
analysis using cryo-electron microscopy.
PMID- 28505111
TI - Effects of Mead Wort Heat Treatment on the Mead Fermentation Process and
Antioxidant Activity.
AB - The effects of mead wort heat treatment on the mead fermentation process and
antioxidant activity were tested. The experiment was conducted with the use of
two different honeys (multiflorous and honeydew) collected from the Lower Silesia
region (Poland). Heat treatment was performed with the use of a traditional
technique (gently boiling), the more commonly used pasteurization, and without
heat treatment (control). During the experiment fermentation dynamics were
monitored using high performance liquid chromatography with refractive index
detection (HPLC-RID). Total antioxidant capacity (TAC) and total phenolic content
(TPC) were estimated for worts and meads using UV/Vis spectrophotometric
analysis. The formation of 5-hydroxymethylfurfural (HMF) was monitored by HPLC
analyses. Heat treatment had a great impact on the final antioxidant capacity of
meads.
PMID- 28505110
TI - Green Tea Polyphenols, Mimicking the Effects of Dietary Restriction, Ameliorate
High-Fat Diet-Induced Kidney Injury via Regulating Autophagy Flux.
AB - Epidemiological and experimental studies reveal that Western dietary patterns
contribute to chronic kidney disease, whereas dietary restriction (DR) or dietary
polyphenols such as green tea polyphenols (GTPs) can ameliorate the progression
of kidney injury. This study aimed to investigate the renal protective effects of
GTPs and explore the underlying mechanisms. Sixty Wistar rats were randomly
divided into 6 groups: standard diet (STD), DR, high-fat diet (HFD), and three
diets plus 200 mg/kg(bw)/day GTPs, respectively. After 18 weeks, HFD group
exhibited renal injuries by increased serum cystatin C levels and urinary N
acetyl-beta-d-glucosaminidase activity, which can be ameliorated by GTPs.
Meanwhile, autophagy impairment as denoted by autophagy-lysosome related
proteins, including LC3-II, Beclin-1, p62, cathepsin B, cathepsin D and LAMP-1,
was observed in HFD group, whereas DR or GTPs promoted renal autophagy activities
and GTPs ameliorated HFD-induced autophagy impairment. In vitro, autophagy flux
suppression was detected in palmitic acid (PA)-treated human proximal tubular
epithelial cells (HK-2), which was ameliorated by epigallocatechin-3-gallate
(EGCG). Furthermore, GTPs (or EGCG) elevated phosphorylation of AMP-activated
protein kinase in the kidneys of HFD-treated rats and in PA-treated HK-2 cells.
These findings revealed that GTPs mimic the effects of DR to induce autophagy and
exert a renal protective effect by alleviating HFD-induced autophagy suppression.
PMID- 28505112
TI - Optimizing the Readout of Lanthanide-DOTA Complexes for the Detection of Ligand
Bound Copper(I).
AB - The CuAAC 'click' reaction was used to couple alkyne-functionalized lanthanide
DOTA complexes to a range of fluorescent antennae. Screening of the antenna
components was aided by comparison of the luminescent output of the resultant
sensors using data normalized to account for reaction conversion as assessed by
IR. A maximum 82-fold enhanced signal:background luminescence output was achieved
using a Eu(III)-DOTA complex coupled to a coumarin-azide, in a reaction which is
specific to the presence of copper(I). This optimized complex provides a new lead
design for lanthanide-DOTA complexes which can act as irreversible 'turn-on'
catalytic sensors for the detection of ligand-bound copper(I).
PMID- 28505113
TI - Evaluation of Efficient and Practical Methods for the Preparation of
Functionalized Aliphatic Trifluoromethyl Ethers.
AB - The "chlorination/fluorination" technique for aliphatic trifluoromethyl ether
synthesis was investigated and a range of products with various functional groups
was prepared. The results were compared with oxidative desulfurization
fluorination of xanthates with the same structure.
PMID- 28505115
TI - Photosensor-Based Latency Measurement System for Head-Mounted Displays.
AB - In this paper, a photosensor-based latency measurement system for head-mounted
displays (HMDs) is proposed. The motion-to-photon latency is the greatest reason
for motion sickness and dizziness felt by users when wearing an HMD system.
Therefore, a measurement system is required to accurately measure and analyze the
latency to reduce these problems. The existing measurement system does not
consider the actual physical movement in humans, and its accuracy is also very
low. However, the proposed system considers the physical head movement and is
highly accurate. Specifically, it consists of a head position model-based rotary
platform, pixel luminance change detector, and signal analysis and calculation
modules. Using these modules, the proposed system can exactly measure the
latency, which is the time difference between the physical movement for a user
and the luminance change of an output image. In the experiment using a commercial
HMD, the latency was measured to be up to 47.05 ms. In addition, the measured
latency increased up to 381.17 ms when increasing the rendering workload in the
HMD.
PMID- 28505114
TI - Osteopontin Deficiency Suppresses Intestinal Tumor Development in Apc-Deficient
Min Mice.
AB - Osteopontin (OPN) is a secreted phosphoglycoprotein, and is a transcriptional
target of aberrant Wnt signaling. OPN is upregulated in human colon cancers, and
is suggested to enhance cancer progression. In this study, the effect of
deficiency of OPN on intestinal tumor development in Apc-deficient Min mice was
investigated. At 16 weeks of age, the number of small intestinal polyps in
Min/OPN(+/-) and Min/OPN(-/-) mice was lower than that of Min/OPN(+/+) mice.
Colorectal tumor incidences and multiplicities in Min/OPN(+/-) and Min/OPN(-/-)
mice were significantly lower than those in Min/OPN(+/+) mice, being 48% and 0.6
+/- 0.8, 50% and 0.8 +/- 0.9 vs. 80% and 1.6 +/- 1.7, respectively. OPN
expression in colorectal tumors was strongly upregulated in Min/OPN(+/+) compared
to adjacent non-tumor parts, but was decreased in Min/OPN(+/-) and not detected
in Min/OPN(-/-). Targets of OPN, matrix metalloproteinases (MMPs)-3, -9, and -13
were lowered by OPN deficiency. Macrophage marker F4/80 in colorectal tumors was
also lowered by OPN deficiency. MMP-9 expression was observed in tumor cells and
tumor-infiltrating neutrophils. These results indicate that induction of OPN by
aberrant Wnt signaling could enhance colorectal tumor development in part by
upregulation of MMP-3, -9, and -13 and infiltration of macrophage and
neutrophils. Suppression of OPN expression could contribute to tumor prevention,
but complete deficiency of OPN may cause some adverse effects.
PMID- 28505116
TI - Surface Modification and Damage of MeV-Energy Heavy Ion Irradiation on Gold
Nanowires.
AB - Gold nanowires with diameters ranging from 20 to 90 nm were fabricated by the
electrochemical deposition technique in etched ion track polycarbonate templates
and were then irradiated by Xe and Kr ions with the energy in MeV range. The
surface modification of nanowires was studied by scanning electron microscopy
(SEM) and transmission electron microscopy (TEM) characterizations. Different
craters with and without protrusion on the gold nanowires were analyzed, and the
two corresponding formation mechanisms, i.e., plastic flow and micro-explosion,
were investigated. In addition, the sputtered gold nanoparticles caused by ion
irradiation were studied and it was confirmed that the surface damage produced in
gold nanowires was increased as the diameter of the nanowires decreased. It was
also found that heavy ion irradiation can also create stacking fault tetrahedrons
(SFTs) in gold nanowires and three different SFTs were confirmed in irradiated
nanowires. A statistical analysis of the size distribution of SFTs in gold
nanowires proved that the average size distribution of SFT was positively related
to the nuclear stopping power of incident ions, i.e., the higher nuclear stopping
power of incident ions could generate SFT with a larger average size in gold
nanowires.
PMID- 28505118
TI - Communicatively Constructing the Bright and Dark Sides of Hope: Family
Caregivers' Experiences during End of Life Cancer Care.
AB - (1) Background: The communication of hope is complicated, particularly for family
caregivers in the context of cancer who struggle to maintain hope for themselves
and their loved ones in the face of terminality. In order to understand these
complexities, the current study examines the bright and dark sides of how hope is
communicated across the cancer journey from the vantage point of bereaved family
caregivers; (2) Methods: We analyzed interviews with bereaved family caregivers
using qualitative thematic and case oriented strategies to identify patterns in
the positive and negative lived experiences when communicating about hope at the
end of life; (3) Results: Two overarching patterns of hope emerged. Those who
experienced hope as particularized (focused on cure) cited communication about
false hope, performing (faking it), and avoidance. Those who transitioned from
particularized to generalized hope (hope for a good death) reported acceptance,
the communication of hope as social support, prioritizing family, and balancing
hope and honesty; (4) Conclusion: Family caregivers face myriad complexities in
managing the bright and dark sides of hope. Interventions should encourage
concurrent oncological and palliative care, increased perspective-taking among
family members, and encourage the transition from particularized to generalized
hope.
PMID- 28505119
TI - Laxative Effects of Dietary Supplementation with Sujiaonori Algal Biomaterial in
Japanese Adult Women with Functional Constipation: A Case Study.
AB - Constipation is a gastrointestinal motility disorder that represents a major
health problem in Japan. Approximately 26% of young Japanese adult women are
reported to have this complaint. We report on the health effects of daily intake
of Sujiaonori algal biomaterial (SBM) on constipation on 12 Japanese adult women.
Data are from a four-week dietary intervention study on the health effects of
daily Sujiaonori supplementation on cardiovascular, skin, and gastrointestinal
health in which 32 adult Japanese volunteers (age range: 20-54 years)
participated. They underwent clinical and laboratory investigations, and
completed two study questionnaires (the brief diet history questionnaire (BDHQ)
and the current health questionnaire) before and after dietary intervention. Of
the 12 women volunteers with functional constipation, there were six SBM
supplemented subjects who received 3 g of Sujiaonori powder twice daily during
meal, whereas the six others (controls) were from the group of those who took 3 g
of a power made of 70% corn starch and 30% Japanese spinach mixture. The analysis
of data on daily nutrient intake showed no significant dietary changes for
nutrients (minerals, proteins, fiber, fat) and calorie intake (except alcohol
intake that was reduced) in both groups. In SBM group, a significant reduction of
the proportion of women with constipation was observed (p < 0.001), whereas no
significant change was noted within the control group (p > 0.05). When both
groups were compared, SBM was more effective than the control product; 66.7%
(4/6) of SBM-supplemented women had their constipation relieved, whereas only one
control (16.7%) controls benefited from dietary intervention (p < 0.001). In
addition, no adverse effect was reported in the SBM group, whereas two controls
reported nausea at post-survey. These results suggest that Sujiaonori contains
compounds that can improve gastrointestinal function and relieve constipation.
PMID- 28505117
TI - HIV-Enhancing and HIV-Inhibiting Properties of Cationic Peptides and Proteins.
AB - Cationic antimicrobial peptides and proteins have historically been ascribed
roles in innate immunity that infer killing of microbial and viral pathogens and
protection of the host. In the context of sexually transmitted HIV-1, we take an
unconventional approach that questions this paradigm. It is becoming increasingly
apparent that many of the cationic polypeptides present in the human genital or
anorectal mucosa, or human semen, are capable of enhancing HIV-1 infection, often
in addition to other reported roles as viral inhibitors. We explore how the in
vivo environment may select for or against the HIV-enhancing aspects of these
cationic polypeptides by focusing on biological relevance. We stress that the
distinction between enhancing and inhibiting HIV-1 infection is not mutually
exclusive to specific classes of cationic polypeptides. Understanding how virally
enhancing peptides and proteins act to promote sexual transmission of HIV-1 would
be important for the design of topical microbicides, mucosal vaccines, and other
preventative measures.
PMID- 28505120
TI - In Situ Raman Analysis of CO2-Assisted Drying of Fruit-Slices.
AB - This work explores the feasibility of applying in situ Raman spectroscopy for the
online monitoring of the supercritical carbon dioxide (SC-CO2) drying of fruits.
Specifically, we investigate two types of fruits: mango and persimmon. The drying
experiments were carried out inside an optical accessible vessel at 10 MPa and
313 K. The Raman spectra reveal: (i) the reduction of the water from the fruit
slice and (ii) the change of the fruit matrix structure during the drying
process. Two different Raman excitation wavelengths were compared: 532 nm and 785
nm. With respect to the quality of the obtained spectra, the 532 nm excitation
wavelength was superior due to a higher signal-to-noise ratio and due to a
resonant excitation scheme of the carotenoid molecules. It was found that the
absorption of CO2 into the fruit matrix enhances the extraction of water, which
was expressed by the obtained drying kinetic curve.
PMID- 28505122
TI - Dynamic and Steady Characteristics of Polymer-Ceramic Pressure-Sensitive Paint
with Variation in Layer Thickness.
AB - Polymer-ceramic pressure-sensitive paint (PC-PSP) has been investigated as a
surface-pressure sensor for unsteady aerodynamics and short duration
measurements. This PSP provides a fast response to a change in pressures with a
spray-coating ability. Because it is sprayed onto an aerodynamic surface, the
thickness of PC-PSP may play an important role in determining the performance of
this sensor. The thickness of other fast PSPs, such as anodized aluminum pressure
sensitive paint, is a major factor in determining its performance. We vary the
thickness of PC-PSP from 10 to 240 MUm in order to study its effects on PSP
measurement characteristics including time response, signal level, pressure
sensitivity, and temperature dependency. It is found that the thickness does
affect these characteristics. However, a thickness over 80 MUm provides uniform
performance in these characteristics.
PMID- 28505121
TI - Molecular Pathways Involved in the Amelioration of Myocardial Injury in Diabetic
Rats by Kaempferol.
AB - There is growing evidence that chronic hyperglycemia leads to the formation of
advanced glycation end products (AGEs) which exerts its effect via interaction
with the receptor for advanced glycation end products (RAGE). AGE-RAGE activation
results in oxidative stress and inflammation. It is well known that this
mechanism is involved in the pathogenesis of cardiovascular disease in diabetes.
Kaempferol, a dietary flavonoid, is known to possess antioxidant, anti-apoptotic,
and anti-inflammatory activities. However, little is known about the effect of
kaempferol on myocardial ischemia-reperfusion (IR) injury in diabetic rats.
Diabetes was induced in male albino Wistar rats using streptozotocin (70 mg/kg;
i.p.), and rats with glucose level >250 mg/dL were considered as diabetic.
Diabetic rats were treated with vehicle (2 mL/kg; i.p.) and kaempferol (20 mg/kg;
i.p.) daily for a period of 28 days and on the 28th day, ischemia was produced by
one-stage ligation of the left anterior descending coronary artery for 45 min
followed by reperfusion for 60 min. After completion of surgery, rats were
sacrificed and the heart tissue was processed for biochemical, morphological, and
molecular studies. Kaempferol pretreatment significantly reduced hyperglycemia,
maintained hemodynamic function, suppressed AGE-RAGE axis activation, normalized
oxidative stress, and preserved morphological alterations. In addition, there was
decreased level of inflammatory markers (tumor necrosis factor-alpha (TNF-alpha),
interleukin-6 (IL-6), and NF-kappaB), inhibition of active c-Jun N-terminal
kinase (JNK) and p38 proteins, and activation of Extracellular signal regulated
kinase 1/2 (ERK1/2) a prosurvival kinase. Furthermore, it also attenuated
apoptosis by reducing the expression of pro-apoptotic proteins (Bax and Caspase
3), Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive
cells, and increasing the level of anti-apoptotic protein (Bcl-2). In conclusion,
kaempferol attenuated myocardial ischemia-reperfusion injury in diabetic rats by
reducing AGE-RAGE/ mitogen activated protein kinase (MAPK) induced oxidative
stress and inflammation.
PMID- 28505123
TI - Perceived Health Benefits and Willingness to Pay for Parks by Park Users:
Quantitative and Qualitative Research.
AB - Whilst a growing body of evidence demonstrates people derive a range of health
and wellbeing benefits from visiting parks, only a limited number of attempts
have been made to provide a complementary economic assessment of parks. The aim
of this exploratory study was to directly estimate the perceived health and
wellbeing benefits attained from parks and the economic value assigned to parks
by park users in Victoria, Australia. The research employed a mixed methods
approach (survey and interviews) to collect primary data from a selection of 140
park users: 100 from two metropolitan parks in Melbourne and 40 from a park on
the urban fringe of Melbourne, Victoria. Our findings suggest that park users
derive a range of perceived physical, mental/spiritual, and social health
benefits, but park use was predominantly associated with physical health
benefits. Overall, our exploratory study findings suggest that park users are
willing to pay for parks, as they highly value them as places for exercising,
socialising, and relaxing. Importantly, most people would miss parks if they did
not exist. The findings aim to provide park managers, public health advocates,
and urban policy makers with evidence about the perceived health and wellbeing
benefits of park usage and the economic value park visitors place on parks.
PMID- 28505124
TI - Structure-Activity Relationships of Bioengineered Heparin/Heparan Sulfates
Produced in Different Bioreactors.
AB - Heparin and heparan sulfate are structurally-related carbohydrates with
therapeutic applications in anticoagulation, drug delivery, and regenerative
medicine. This study explored the effect of different bioreactor conditions on
the production of heparin/heparan sulfate chains via the recombinant expression
of serglycin in mammalian cells. Tissue culture flasks and continuously-stirred
tank reactors promoted the production of serglycin decorated with heparin/heparan
sulfate, as well as chondroitin sulfate, while the serglycin secreted by cells in
the tissue culture flasks produced more highly-sulfated heparin/heparan sulfate
chains. The serglycin produced in tissue culture flasks was effective in binding
and signaling fibroblast growth factor 2, indicating the utility of this molecule
in drug delivery and regenerative medicine applications in addition to its well
known anticoagulant activity.
PMID- 28505125
TI - Isolaurenidificin and Bromlaurenidificin, Two New C15-Acetogenins from the Red
Alga Laurencia obtusa.
AB - Chromatographic fractionation of the CH2Cl2/MeOH extract of the Red Sea red alga
Laurencia obtusa gave two new hexahydrofuro[3,2-b]furan-based C15-acetogenins,
namely, isolaurenidificin (1) and bromlaurenidificin (2). The chemical structures
were elucidated based on extensive analyses of their spectral data. Compounds 1
and 2 showed no toxicity (LC50 > 12 mM) using Artemia salina as test organism.
Both compounds showed weak cytotoxicity against A549, HepG-2, HCT116, MCF-7, and
PC-3 cells, however, they exhibited a relatively potent cytotoxic activity
against peripheral blood neutrophils. This can be attributed partly to induction
of apoptosis.
PMID- 28505126
TI - Unprocessed Meat Consumption and Incident Cardiovascular Diseases in Korean
Adults: The Korean Genome and Epidemiology Study (KoGES).
AB - Meat consumption has been shown to be associated with cardiovascular disease
(CVD) risk in Western societies; however, epidemiological data are limited on the
Korean population. Therefore, we examined the associations between unprocessed
meat consumption and CVD incidence in Korea. Data were derived from the Ansung
Ansan cohort (2001-2012), including 9370 adults (40-69 years) without CVD or
cancer at baseline. Total unprocessed meat consumption was estimated as the sum
of unprocessed red meat (beef, pork, and organ meat) and poultry consumption. In
the fully adjusted Cox regression model, the relative risks of CVD across
increasing quintiles of total unprocessed meat intake were 1.0 (reference), 0.72
(95% confidence interval (CI): 0.55, 0.95), 0.57 (95% CI: 0.42, 0.78), 0.69 (95%
CI: 0.51, 0.95), and 0.69 (95% CI: 0.48, 0.97), but no significant linear trend
was detected (p for trend = 0.14). Frequent poultry consumption was significantly
associated with a decreased CVD risk; this association showed a dose-response
relationship (p for trend = 0.04). This study showed that a moderate intake of
total unprocessed meat was inversely associated with CVD risk. A significant
inverse association between poultry consumption and incident CVD was observed in
Korean adults, requiring further confirmation in other populations.
PMID- 28505127
TI - Variability of DNA Methylation within Schizophrenia Risk Loci across Subregions
of Human Hippocampus.
AB - Identification of 108 genomic regions significantly associated with schizophrenia
risk by the Psychiatric Genomics Consortium was a milestone for the field, and
much work is now focused on determining the mechanism of risk associated with
each locus. Within these regions, we investigated variability of DNA methylation,
a low-level cellular phenotype closely linked to genotype, in two highly similar
cellular populations sampled from the human hippocampus, to draw inferences about
the elaboration of genotype to phenotype within these loci enriched for
schizophrenia risk. DNA methylation was assessed with the Illumina
HumanMethylation450 BeadArray in tissue laser-microdissected from the stratum
oriens of subfield CA1 or CA2/3, regions having unique connectivity with
intrinsic and extrinsic fiber systems within the hippocampus. Samples consisted
of postmortem human hippocampus tissue from eight schizophrenia patients, eight
bipolar disorder patients, and eight healthy control subjects. Within these
genomic regions, we observed far greater difference in methylation patterns
between circuit locations within subjects than in a single subregion between
subjects across diagnostic groups, demonstrating the complexity of genotype to
phenotype elaboration across the diverse circuitry of the human brain.
PMID- 28505129
TI - Assessment of Antimicrobial and Antioxidant Activities of Nepeta trachonitica:
Analysis of Its Phenolic Compounds Using HPLC-MS/MS.
AB - Continuing our work on the sources of natural bioactive compounds, we evaluated
the antimicrobial and antioxidant activities of Nepeta trachonitica as well as
its major phenolic content using the high-performance liquid chromatography-mass
spectrometry/mass spectrometry (HPLC-MS/MS) technique. For antioxidant activity,
ferric reducing antioxidant power (FRAP) and cupric ion reducing antioxidant
capacity (CUPRAC) methods were performed to measure the reducing power and 1,1
diphenyl-2-picrylhydrazyl (DPPH) assay was employed to evaluate the radical
scavenging activity of the sample. For antimicrobial activity, three Gram
positive and four Gram-negative microbial species as well as three fungi species
were tested. N. trachonitica appeared to have reasonable antioxidant activity and
decent antimicrobial activity as indicated by the inhibition of the organisms'
growth. The most susceptible species were Bacillus subtilis ATCC 6633 and
Escherichia coli ATCC 11229 among the organisms tested. Ethanol extract of the
plant has the highest effect on Saccharomyces cerevisiae but no effect on
Yarrowia lipolytica. The HPLC-MS/MS analysis showed that at least 11 major
phenolic compounds of N. trachonitica exist, the major ones being rosmarinic
acid, chlorogenic acid and quinic acid. The obtained results suggest that N.
trachonitica could be a promising source for food and nutraceutical industries
because of its antimicrobial and antioxidant properties and phenolic compounds.
PMID- 28505130
TI - A Review of Microwave Thermography Nondestructive Testing and Evaluation.
AB - Microwave thermography (MWT) has many advantages including strong penetrability,
selective heating, volumetric heating, significant energy savings, uniform
heating, and good thermal efficiency. MWT has received growing interest due to
its potential to overcome some of the limitations of microwave nondestructive
testing (NDT) and thermal NDT. Moreover, during the last few decades MWT has
attracted growing interest in materials assessment. In this paper, a
comprehensive review of MWT techniques for materials evaluation is conducted
based on a detailed literature survey. First, the basic principles of MWT are
described. Different types of MWT, including microwave pulsed thermography,
microwave step thermography, microwave pulsed phase thermography, and microwave
lock-in thermography are defined and introduced. Then, MWT case studies are
discussed. Next, comparisons with other thermography and NDT methods are
conducted. Finally, the trends in MWT research are outlined, including new
theoretical studies, simulations and modelling, signal processing algorithms,
internal properties characterization, automatic separation and inspection
systems. This work provides a summary of MWT, which can be utilized for material
failures prevention and quality control.
PMID- 28505131
TI - Reduction of the Influence of Laser Beam Directional Dithering in a Laser
Triangulation Displacement Probe.
AB - Directional dithering of a laser beam potentially limits the detection accuracy
of a laser triangulation displacement probe. A theoretical analysis indicates
that the measurement accuracy will linearly decrease as the laser dithering angle
increases. To suppress laser dithering, a scheme for reduction of the influence
of laser beam directional dithering in a laser triangulation displacement probe,
which consists of a collimated red laser, a laser beam pointing control setup, a
receiver lens, and a charge-coupled device, is proposed in this paper. The laser
beam pointing control setup is inserted into the source laser beam and the
measured object and can separate the source laser beam into two symmetrical laser
beams. Hence, at the angle at which the source laser beam dithers, the positional
averages of the two laser spots are equal and opposite. Moreover, a virtual
linear function method is used to maintain a stable average of the positions of
the two spots on the imaging side. Experimental results indicate that with laser
beam pointing control, the estimated standard deviation of the fitting error
decreases from 0.3531 mm to 0.0100 mm , the repeatability accuracy can be lowered
from +/-7 mm to +/-5 MU m , and the nonlinear error can be reduced from +/-6 % FS
(full scale) to +/-0.16 % FS.
PMID- 28505132
TI - Preparation and Characterization of Chitosan Obtained from Shells of Shrimp
(Litopenaeus vannamei Boone).
AB - The main source of commercial chitosan is the extensive deacetylation of its
parent polymer chitin. It is present in green algae, the cell walls or fungi and
in the exoskeleton of crustaceans. A novel procedure for preparing chitosan from
shrimp shells was developed. The procedure involves two 10-minutes bleaching
steps with ethanol after the usual demineralization and deproteinization
processes. Before deacetylation, chitin was immersed in 12.5 M NaOH, cooled down
and kept frozen for 24 h. The obtained chitosan was characterized using scanning
electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), UV, X
ray diffraction (XRD) and viscosimetry. Samples of white chitosan with
acetylation degrees below 9 % were obtained, as determined by FTIR and UV-first
derivative spectroscopy. The change in the morphology of samples was followed by
SEM. The ash content of chitosan samples were all below 0.063 % . Chitosan was
soluble in 1 % acetic acid with insoluble contents of 0.62 % or less. XRD
patterns exhibited the characteristic peaks of chitosan centered at 10 and 20
degrees in 2 theta . The molecular weight of chitosan was between 2.3 and 2.8 *
10 5 g/mol. It is concluded that the procedure developed in the present work
allowed obtaining chitosans with physical and chemical properties suitable for
pharmaceutical applications.
PMID- 28505133
TI - Macronutrient Intake and Risk of Crohn's Disease: Systematic Review and Dose
Response Meta-Analysis of Epidemiological Studies.
AB - Dietary intake is potentially associated with the onset of Crohn's disease (CD),
but evidence from epidemiological studies has remained unclear. This study aimed
to evaluate the role of macronutrient intake in the development of CD. A
systematic search was conducted in PubMed and Web of Science to identify all
relevant studies, and the role of macronutrients in the development of CD was
quantitatively assessed by dose-response meta-analysis. Four case-control studies
(a total of 311 CD cases and 660 controls) and five prospective cohort studies
(238,887 participants and 482 cases) were identified. The pooled relative risks
(RR) for per 10 g increment/day were 0.991 (95% confidence interval (CI): 0.978
1.004) for total carbohydrate intake, 1.018 (95% CI: 0.969-1.069) for total fat
intake, and 1.029 (95% CI: 0.955-1.109) for total protein intake. Fiber intake
was inversely associated with CD risk (RR for per 10 g increment/day: 0.853, 95%
CI: 0.762-0.955), but the association was influenced by study design and smoking
adjustment. In subtypes, sucrose intake was positively related with CD risk (RR
for per 10 g increment/day: 1.088, 95% CI: 1.020-1.160). Non-linear dose-response
association was also found between fiber and sucrose intake and CD risk. In
conclusion, this meta-analysis suggested a lack of association between total
carbohydrate, fat or protein intake and the risk of CD, while high fiber intake
might decrease the risk. In subtypes, high sucrose intake might increase the risk
of CD.
PMID- 28505135
TI - Sea Ice Detection Based on an Improved Similarity Measurement Method Using
Hyperspectral Data.
AB - Hyperspectral remote sensing technology can acquire nearly continuous spectrum
information and rich sea ice image information, thus providing an important means
of sea ice detection. However, the correlation and redundancy among hyperspectral
bands reduce the accuracy of traditional sea ice detection methods. Based on the
spectral characteristics of sea ice, this study presents an improved similarity
measurement method based on linear prediction (ISMLP) to detect sea ice. First,
the first original band with a large amount of information is determined based on
mutual information theory. Subsequently, a second original band with the least
similarity is chosen by the spectral correlation measuring method. Finally,
subsequent bands are selected through the linear prediction method, and a support
vector machine classifier model is applied to classify sea ice. In experiments
performed on images of Baffin Bay and Bohai Bay, comparative analyses were
conducted to compare the proposed method and traditional sea ice detection
methods. Our proposed ISMLP method achieved the highest classification accuracies
(91.18% and 94.22%) in both experiments. From these results the ISMLP method
exhibits better performance overall than other methods and can be effectively
applied to hyperspectral sea ice detection.
PMID- 28505128
TI - A Proposal for a Study on Treatment Selection and Lifestyle Recommendations in
Chronic Inflammatory Diseases: A Danish Multidisciplinary Collaboration on
Prognostic Factors and Personalised Medicine.
AB - Chronic inflammatory diseases (CIDs), including Crohn's disease and ulcerative
colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis,
psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune
mediated uveitis, are treated with biologics targeting the pro-inflammatory
molecule tumour necrosis factor-alpha (TNF) (i.e., TNF inhibitors). Approximately
one-third of the patients do not respond to the treatment. Genetics and lifestyle
may affect the treatment results. The aims of this multidisciplinary
collaboration are to identify (1) molecular signatures of prognostic value to
help tailor treatment decisions to an individual likely to initiate TNF inhibitor
therapy, followed by (2) lifestyle factors that support achievement of optimised
treatment outcome. This report describes the establishment of a cohort that aims
to obtain this information. Clinical data including lifestyle and treatment
response and biological specimens (blood, faeces, urine, and, in IBD patients,
intestinal biopsies) are sampled prior to and while on TNF inhibitor therapy.
Both hypothesis-driven and data-driven analyses will be performed according to
pre-specified protocols including pathway analyses resulting from candidate gene
expression analyses and global approaches (e.g., metabolomics, metagenomics,
proteomics). The final purpose is to improve the lives of patients suffering from
CIDs, by providing tools facilitating treatment selection and dietary
recommendations likely to improve the clinical outcome.
PMID- 28505134
TI - A Novel Roseosiphophage Isolated from the Oligotrophic South China Sea.
AB - The Roseobacter clade is abundant and widespread in marine environments and plays
an important role in oceanic biogeochemical cycling. In this present study, a
lytic siphophage (labeled vB_DshS-R5C) infecting the strain type of
Dinoroseobacter shibae named DFL12T, which is part of the Roseobacter clade, was
isolated from the oligotrophic South China Sea. Phage R5C showed a narrow host
range, short latent period and low burst size. The genome length of phage R5C was
77, 874 bp with a G+C content of 61.5%. Genomic comparisons detected no genome
matches in the GenBank database and phylogenetic analysis based on DNA polymerase
I revealed phylogenetic features that were distinct to other phages, suggesting
the novelty of R5C. Several auxiliary metabolic genes (e.g., phoH gene, heat
shock protein and queuosine biosynthesis genes) were identified in the R5C genome
that may be beneficial to the host and/or offer a competitive advantage for the
phage. Among siphophages infecting the Roseobacter clade (roseosiphophages), four
gene transfer agent-like genes were commonly located with close proximity to
structural genes, suggesting that their function may be related to the tail of
siphoviruses. The isolation and characterization of R5C demonstrated the high
genomic and physiological diversity of roseophages as well as improved our
understanding of host-phage interactions and the ecology of the marine
Roseobacter.
PMID- 28505137
TI - Airborne Infrared and Visible Image Fusion Combined with Region Segmentation.
AB - This paper proposes an infrared (IR) and visible image fusion method introducing
region segmentation into the dual-tree complex wavelet transform (DTCWT) region.
This method should effectively improve both the target indication and scene
spectrum features of fusion images, and the target identification and tracking
reliability of fusion system, on an airborne photoelectric platform. The method
involves segmenting the region in an IR image by significance, and identifying
the target region and the background region; then, fusing the low-frequency
components in the DTCWT region according to the region segmentation result. For
high-frequency components, the region weights need to be assigned by the
information richness of region details to conduct fusion based on both weights
and adaptive phases, and then introducing a shrinkage function to suppress noise;
Finally, the fused low-frequency and high-frequency components are reconstructed
to obtain the fusion image. The experimental results show that the proposed
method can fully extract complementary information from the source images to
obtain a fusion image with good target indication and rich information on scene
details. They also give a fusion result superior to existing popular fusion
methods, based on eithers subjective or objective evaluation. With good stability
and high fusion accuracy, this method can meet the fusion requirements of IR
visible image fusion systems.
PMID- 28505136
TI - Gubenyiliu II Inhibits Breast Tumor Growth and Metastasis Associated with
Decreased Heparanase Expression and Phosphorylation of ERK and AKT Pathways.
AB - Gubenyiliu II (GYII), a Traditional Chinese Medicine (TCM) formula used in our
hospital, has shown beneficial effects in cancer patients. In this study, we
investigated the molecular mechanisms underlying the beneficial effects of GYII
on murine breast cancer models. GYII showed significant inhibitory effects on
tumor growth and metastasis in the murine breast cancer model. Additionally, GYII
suppressed the proliferation of 4T1 and MCF-7 cells in a dose-dependent manner. A
better inhibitory effect on 4T1 cell proliferation and migration was found in the
decomposed recipes (DR) of GYII. Moreover, heparanase expression and the degree
of angiogenesis were reduced in tumor tissues. Western blot analysis showed
decreased expression of heparanase and growth factors in the cells treated with
GYII and its decomposed recipes (DR2 and DR3), and thereby a reduction in the
phosphorylation of extracellular signal-regulated kinase (ERK) and serine
threonine kinase (AKT). These results suggest that GYII exerts anti-tumor growth
and anti-metastatic effects in the murine breast cancer model. The anti-tumor
activity of GYII and its decomposed recipes is, at least partly, associated with
decreased heparanase and growth factor expression, which subsequently suppressed
the activation of the ERK and AKT pathways.
PMID- 28505138
TI - Estimating Density and Temperature Dependence of Juvenile Vital Rates Using a
Hidden Markov Model.
AB - Organisms in the wild have cryptic life stages that are sensitive to changing
environmental conditions and can be difficult to survey. In this study, I used
mark-recapture methods to repeatedly survey Anaea aidea (Nymphalidae)
caterpillars in nature, then modeled caterpillar demography as a hidden Markov
process to assess if temporal variability in temperature and density influence
the survival and growth of A. aidea over time. Individual encounter histories
result from the joint likelihood of being alive and observed in a particular
stage, and I have included hidden states by separating demography and
observations into parallel and independent processes. I constructed a demographic
matrix containing the probabilities of all possible fates for each stage,
including hidden states, e.g., eggs and pupae. I observed both dead and live
caterpillars with high probability. Peak caterpillar abundance attracted multiple
predators, and survival of fifth instars declined as per capita predation rate
increased through spring. A time lag between predator and prey abundance was
likely the cause of improved fifth instar survival estimated at high density.
Growth rates showed an increase with temperature, but the preferred model did not
include temperature. This work illustrates how state-space models can include
unobservable stages and hidden state processes to evaluate how environmental
factors influence vital rates of cryptic life stages in the wild.
PMID- 28505140
TI - Self-Management Group Exercise Extends Healthy Life Expectancy in Frail Community
Dwelling Older Adults.
AB - Preventing frailty and its adverse health outcomes is crucial in countries with a
large elderly population, such as Japan. Since the long-term care insurance
(LTCI) system was launched, the number of certified older adults with LTCI
service requirement has continued to increase. This is a serious problem, because
the LTCI service requirement certification is equivalent to disability. The aim
of this study was to evaluate the effect of a self-management group intervention
on new LTCI service requirement certifications in community-dwelling older adults
in Japan. We analyzed the cohort data from a prospective study. In this study, we
recruited community-dwelling adults aged 65 years and older who were independent
in a city in Kyoto prefecture in 2012. The subjects in the participation group (n
= 1620) attended 60-min group training sessions once or twice every two weeks
from December 2012 to December 2016. The exercise sessions consisted of mild
intensity aerobic exercise, mild strength training, flexibility and balance
exercises, and cool-down activities. These exercise classes were facilitated by
well-trained volunteer staff. The outcome measure was the number of new LTCI
requirement certifications during a four-year follow-up period. During the four
year follow-up period, 247 subjects (15.2%) in the participation group and 334
(20.6%) in the control group were newly certified for LTCI service requirements.
The hazard ratio for new LTCI service requirements in the participation group
compared with the control group was 0.73 (95% CI = 0.62-0.86) in the four-year
follow-up period. These results indicate the usefulness of self-management group
exercise to reduce the incidence of disability in older adults. Thus, increasing
self-management group activities in each community should be encouraged.
PMID- 28505139
TI - Mental Health Problems and Related Factors in Ecuadorian College Students.
AB - Although the mental health problems of college students have been the subject of
increasing research, there are no studies about its prevalence in Ecuadorian
college students. The aim of this study was to determine the mental health
problems and their associated factors in Ecuadorian freshmen university students.
A sample of 1092 students (53.7% women; mean age = 18.3 years) were recruited
from the Technical Particular University of Loja (Ecuador). Socio-demographic,
academic, and clinical characteristics were gathered, as well as information on
the participants' mental health through a number of mental health screens.
Prevalence of positive screens was 6.2% for prevalence of major depressive
episodes, 0.02% for generalized anxiety disorders, 2.2% for panic disorders,
32.0% for eating disorders, 13.1% for suicidal risk. Mental health problems were
significantly associated with sex, area of study, self-esteem, social support,
personality and histories of mental health problems. The findings offer a
starting point for identifying useful factors to target prevention and
intervention strategies aimed at university students.
PMID- 28505141
TI - A Decade of Progress toward Ending the Intensive Confinement of Farm Animals in
the United States.
AB - In this paper, the Humane Society of the United States (HSUS) farm animal
protection work over the preceding decade is described from the perspective of
the organization. Prior to 2002, there were few legal protections for animals on
the farm, and in 2005, a new campaign at the HSUS began to advance state ballot
initiatives throughout the country, with a decisive advancement in California
(Proposition 2) that paved the way for further progress. Combining legislative
work with undercover farm and slaughterhouse investigations, litigation and
corporate engagement, the HSUS and fellow animal protection organizations have
made substantial progress in transitioning the veal, pork and egg industries away
from intensive confinement systems that keep the animals in cages and crates.
Investigations have become an important tool for demonstrating widespread
inhumane practices, building public support and convincing the retail sector to
publish meaningful animal welfare policies. While federal legislation protecting
animals on the farm stalled, there has been steady state-by-state progress, and
this is complemented by major brands such as McDonald's and Walmart pledging to
purchase only from suppliers using cage-free and crate-free animal housing
systems. The evolution of societal expectations regarding animals has helped
propel the recent wave of progress and may also be driven, in part, by the work
of animal protection organizations.
PMID- 28505142
TI - Mitochondria Targeting with Luminescent Rhenium(I) Complexes.
AB - Two new neutral fac-[Re(CO)3(phen)L] compounds (1,2), with phen = 1,10
phenanthroline and L = O2C(CH2)5CH3 or O2C(CH2)4C=CH, were synthetized in one-pot
procedures from fac-[Re(CO)3(phen)Cl] and the corresponding carboxylic acids, and
were fully characterized by IR and UV-Vis absorption spectroscopy, 1H- and 13C
NMR, mass spectrometry and X-ray crystallography. The compounds, which display
orange luminescence, were used as probes for living cancer HeLa cell staining.
Confocal microscopy revealed accumulation of both dyes in mitochondria. To
investigate the mechanism of mitochondrial staining, a new non-emissive compound,
fac-[Re(CO)3(phen)L], with L = O2C(CH2)3((C5H5)Fe(C5H4), i.e., containing a
ferrocenyl moiety, was synthetized and characterized (3). 3 shows the same
mitochondrial accumulation pattern as 1 and 2. Emission of 3 can only be possible
when ferrocene-containing ligand dissociates from the metal center to produce a
species containing the luminescent fac-[Re(CO)3(phen)]+ core. The release of
ligands from the Re center was verified in vitro through the conjugation with
model proteins. These findings suggest that the mitochondria accumulation of
compounds 1-3 is due to the formation of luminescent fac-[Re(CO)3(phen)]+
products, which react with cellular matrix molecules giving secondary products
and are uptaken into the negatively charged mitochondrial membranes. Thus,
reported compounds feature a rare dissociation-driven mechanism of action with
great potential for biological applications.
PMID- 28505144
TI - Microbiota and Particulate Matter Assessment in Portuguese Optical Shops
Providing Contact Lens Services.
AB - The aim of this work was to assess the microbiota (fungi and bacteria) and
particulate matter in optical shops, contributing to a specific protocol to
ensure a proper assessment. Air samples were collected through an impaction
method. Surface and equipment swab samples were also collected side-by-side.
Measurements of particulate matter were performed using portable direct-reading
equipment. A walkthrough survey and checklist was also applied in each shop.
Regarding air sampling, eight of the 13 shops analysed were above the legal
requirement and 10 from the 26 surfaces samples were overloaded. In three out of
the 13 shops fungal contamination in the analysed equipment was not detected. The
bacteria air load was above the threshold in one of the 13 analysed shops.
However, bacterial counts were detected in all sampled equipment. Fungi and
bacteria air load suggested to be influencing all of the other surface and
equipment samples. These results reinforce the need to improve air quality, not
only to comply with the legal requirements, but also to ensure proper hygienic
conditions. Public health intervention is needed to assure the quality and safety
of the rooms and equipment in optical shops that perform health interventions in
patients.
PMID- 28505143
TI - The Transcriptome of Type I Murine Astrocytes under Interferon-Gamma Exposure and
Remyelination Stimulus.
AB - Astrocytes are considered to be an important contributor to central nervous
system (CNS) disorders, particularly multiple sclerosis. The transcriptome of
these cells is greatly affected by cytokines released by lymphocytes, penetrating
the blood-brain barrier-in particular, the classical pro-inflammatory cytokine
interferon-gamma (IFNgamma). We report here the transcriptomal profiling of
astrocytes treated using IFNgamma and benztropine, a putative remyelinization
agent. Our findings indicate that the expression of genes involved in antigen
processing and presentation in astrocytes are significantly upregulated upon
IFNgamma exposure, emphasizing the critical role of this cytokine in the
redirection of immune response towards self-antigens. Data reported herein
support previous observations that the IFNgamma-induced JAK-STAT signaling
pathway may be regarded as a valuable target for pharmaceutical interventions.
PMID- 28505145
TI - DNA Methylation Targets Influenced by Bisphenol A and/or Genistein Are Associated
with Survival Outcomes in Breast Cancer Patients.
AB - Early postnatal exposures to Bisphenol A (BPA) and genistein (GEN) have been
reported to predispose for and against mammary cancer, respectively, in adult
rats. Since the changes in cancer susceptibility occurs in the absence of the
original chemical exposure, we have investigated the potential of epigenetics to
account for these changes. DNA methylation studies reveal that prepubertal BPA
exposure alters signaling pathways that contribute to carcinogenesis. Prepubertal
exposure to GEN and BPA + GEN revealed pathways involved in maintenance of
cellular function, indicating that the presence of GEN either reduces or counters
some of the alterations caused by the carcinogenic properties of BPA. We
subsequently evaluated the potential of epigenetic changes in the rat mammary
tissues to predict survival in breast cancer patients via the Cancer Genomic
Atlas (TCGA). We identified 12 genes that showed strong predictive values for
long-term survival in estrogen receptor positive patients. Importantly, two genes
associated with improved long term survival, HPSE and RPS9, were identified to be
hypomethylated in mammary glands of rats exposed prepuberally to GEN or to GEN +
BPA respectively, reinforcing the suggested cancer suppressive properties of GEN.
PMID- 28505146
TI - Upregulated Autophagy in Sertoli Cells of Ethanol-Treated Rats Is Associated with
Induction of Inducible Nitric Oxide Synthase (iNOS), Androgen Receptor
Suppression and Germ Cell Apoptosis.
AB - This study was conducted to investigate the autophagic response of Sertoli cells
(SCs) to acute ethanol toxicity using in vivo and in vitro models. Adult Wistar
rats were intraperitoneally injected with either 5 g/kg ethanol or phosphate
buffered saline (for the control group) and sacrificed 0, 3, 6 and 24 h after
injection. Compared to the control group, enhanced germ cell apoptosis was
observed in the ethanol-treated rats (ETRs) in association with upregulation of
iNOS and reduced expression of androgen receptor protein levels in SCs, which
were resistant to apoptosis. Meanwhile, autophagy was upregulated in ETR SCs
(peaking at 24 h) compared to the control group, as evidenced by transcription
factor EB (TFEB) nuclear translocation, enhanced expression of microtubule
associated protein 1 light chain3-II (LC3-II), lysosome-associated membrane
protein-2 (LAMP-2), pan cathepsin protein levels and reduced expression of p62.
This upregulation of SC autophagy was confirmed ultrastructurally by enhanced
formation of autophagic vacuoles and by immunofluorescent double labelling of
autophagosomal and lysosomal markers. Study of cultured SCs confirmed enhanced
autophagic response to ethanol toxicity, which was cytoprotective based on
decreased viability of SCs upon blocking autophagy with 3-methyladenine (3-MA).
The results highlighted the molecular mechanisms of prosurvival autophagy in ETR
SCs for the first time, and may have significant implications for male fertility.
PMID- 28505147
TI - Changes in the Sodium Content of Australian Processed Foods between 1980 and 2013
Using Analytical Data.
AB - The objective of this study was to obtain analytical data on the sodium content
of a range of processed foods and compare the levels obtained with their label
claims and with published data of the same or equivalent processed foods in the
1980s and 1990s to investigate the extent of any change in sodium content in
relation to reformulation targets. The sodium contents of 130 Australian
processed foods were obtained by inductively coupled plasma optical emission
spectrometry (ICP-OES) analysis and compared with previously published data. The
sodium content between 1980 and 2013 across all products and by each product
category were compared. There was a significant overall sodium reduction of 23%,
181 mg/100 g (p <0.001, 95% CI (Confidence Interval), 90 to 272 mg/100 g), in
Australian processed foods since 1980, with a 12% (83 mg/100 g) reduction over
the last 18 years. The sodium content of convenience foods (p < 0.001, 95% CI, 94
to 291 mg/100 g) and snack foods (p = 0.017, 95% CI, 44 to 398 mg/100 g) had
declined significantly since 1980. Meanwhile, the sodium contents of processed
meats (p = 0.655, 95% CI, -121 to 190) and bread and other bakery products (p =
0.115, 95% CI, -22 to 192) had decreased, though not significantly. Conversely,
the sodium content of cheese (p = 0.781, 95% CI, -484 to 369 mg/100 g) had
increased but also not significantly. Of the 130 products analysed, 62% met
Australian reformulation targets. Sodium contents of the processed foods and the
overall changes in comparison with previous data indicate a decrease over the 33
years period and suggest that the Australian recommended reformulation targets
have been effective. Further sodium reduction of processed foods is still
required and continuous monitoring of the reduction of sodium levels in processed
foods is needed.
PMID- 28505148
TI - Potential Pathogenesis and Biomarkers of Kidney Cancer-Related Stroke.
AB - BACKGROUND Stroke risk and stroke recurrence are increased in cancer patients,
but the pathogenesis and biomarkers of kidney cancer-related stroke (KCS) are
generally unclear. The aim of the present research was to investigate the
pathogenesis and plasma biomarkers of kidney cancer-related stroke. MATERIAL AND
METHODS A retrospective review was conducted on acute stroke patients with kidney
cancer (KC) who were admitted to the hospital between January 2006 and December
2015. A total of 106 patients with KCS (active KC patients with acute stroke but
without conventional vascular risks) were identified. In addition, 106 age- and
sex-matched patients with KC alone were recruited. RESULTS KCS patients had
higher plasma D-dimer, cancer antigen (CA) 125, and CEA levels and greater
proteinuria levels than did KC patients. Multiple logistic regression analysis
showed that the risk of stroke in patients with KC increased independently by
0.8% (odds ratio [OR] 1.008; 95% confidence interval [CI] 1.002, 1.013; p=0.004)
with a 1 ng/mL increase in D-dimer levels, by 1.2% (OR 1.012; 95% CI 1.007,
1.018; p=0.000) with a 1 U/mL increase in CA125, by 2.5% (OR 1.025; 95% CI 1.012,
1.038; p=0.000) with a 1 U/mL increase in CEA by 1.4% (OR 1.014; 95% CI 1.005,
1.024; p=0.004) with a 1 mg increase in urine protein in 24 hours. CONCLUSIONS
Elevated plasma D-dimer, CA125 and CEA levels, and increased urine protein levels
might lead to hypercoagulability and then KCS; however, they may also be
biomarkers of KCS.
PMID- 28505149
TI - Distinct DNA-binding surfaces in the ATPase and linker domains of MutLgamma
determine its substrate specificities and exert separable functions in meiotic
recombination and mismatch repair.
AB - Mlh1-Mlh3 (MutLgamma) is a mismatch repair factor with a central role in
formation of meiotic crossovers, presumably through resolution of double Holliday
junctions. MutLgamma has DNA-binding, nuclease, and ATPase activities, but how
these relate to one another and to in vivo functions are unclear. Here, we
combine biochemical and genetic analyses to characterize Saccharomyces cerevisiae
MutLgamma. Limited proteolysis and atomic force microscopy showed that purified
recombinant MutLgamma undergoes ATP-driven conformational changes. In vitro,
MutLgamma displayed separable DNA-binding activities toward Holliday junctions
(HJ) and, surprisingly, single-stranded DNA (ssDNA), which was not predicted from
current models. MutLgamma bound DNA cooperatively, could bind multiple substrates
simultaneously, and formed higher-order complexes. FeBABE hydroxyl radical
footprinting indicated that the DNA-binding interfaces of MutLgamma for ssDNA and
HJ substrates only partially overlap. Most contacts with HJ substrates were
located in the linker regions of MutLgamma, whereas ssDNA contacts mapped within
linker regions as well as the N-terminal ATPase domains. Using yeast genetic
assays for mismatch repair and meiotic recombination, we found that mutations
within different DNA-binding surfaces exert separable effects in vivo. For
example, mutations within the Mlh1 linker conferred little or no meiotic
phenotype but led to mismatch repair deficiency. Interestingly, mutations in the
N-terminal domain of Mlh1 caused a stronger meiotic defect than mlh1Delta,
suggesting that the mutant proteins retain an activity that interferes with
alternative recombination pathways. Furthermore, mlh3Delta caused more chromosome
missegregation than mlh1Delta, whereas mlh1Delta but not mlh3Delta partially
alleviated meiotic defects of msh5Delta mutants. These findings illustrate
functional differences between Mlh1 and Mlh3 during meiosis and suggest that
their absence impinges on chromosome segregation not only via reduced formation
of crossovers. Taken together, our results offer insights into the structure
function relationships of the MutLgamma complex and reveal unanticipated genetic
relationships between components of the meiotic recombination machinery.
PMID- 28505150
TI - A question of fate.
AB - Ever since the discovery of neural stem cells in the mammalian brain, the
possibility of brain tissue regeneration has captured the minds of scientists,
clinicians, and the public. Neural stem cells have been envisioned as a source of
donor cells for transplantation and vectors for the delivery of gene therapy.
Over the past decade, many researchers have contributed to characterizing these
cells and their lineages, providing the foundation for their utilization as
therapeutic devices. In a new study, Azim and colleagues took a different
approach: using pharmacogenomics to focus on neural stem cell lineage, they
identified specific compounds that can direct neural stem cell fate toward a
specific lineage in vivo, both in physiological and pathological conditions.
Their work opens new avenues for treatment of neurodegenerative and demyelinating
disorders.
PMID- 28505151
TI - Mixture models reveal multiple positional bias types in RNA-Seq data and lead to
accurate transcript concentration estimates.
AB - Accuracy of transcript quantification with RNA-Seq is negatively affected by
positional fragment bias. This article introduces Mix2 (rd. "mixquare"), a
transcript quantification method which uses a mixture of probability
distributions to model and thereby neutralize the effects of positional fragment
bias. The parameters of Mix2 are trained by Expectation Maximization resulting in
simultaneous transcript abundance and bias estimates. We compare Mix2 to
Cufflinks, RSEM, eXpress and PennSeq; state-of-the-art quantification methods
implementing some form of bias correction. On four synthetic biases we show that
the accuracy of Mix2 overall exceeds the accuracy of the other methods and that
its bias estimates converge to the correct solution. We further evaluate Mix2 on
real RNA-Seq data from the Microarray and Sequencing Quality Control (MAQC, SEQC)
Consortia. On MAQC data, Mix2 achieves improved correlation to qPCR measurements
with a relative increase in R2 between 4% and 50%. Mix2 also yields repeatable
concentration estimates across technical replicates with a relative increase in
R2 between 8% and 47% and reduced standard deviation across the full
concentration range. We further observe more accurate detection of differential
expression with a relative increase in true positives between 74% and 378% for 5%
false positives. In addition, Mix2 reveals 5 dominant biases in MAQC data
deviating from the common assumption of a uniform fragment distribution. On SEQC
data, Mix2 yields higher consistency between measured and predicted concentration
ratios. A relative error of 20% or less is obtained for 51% of transcripts by
Mix2, 40% of transcripts by Cufflinks and RSEM and 30% by eXpress. Titration
order consistency is correct for 47% of transcripts for Mix2, 41% for Cufflinks
and RSEM and 34% for eXpress. We, further, observe improved repeatability across
laboratory sites with a relative increase in R2 between 8% and 44% and reduced
standard deviation.
PMID- 28505152
TI - A predictive coding account of bistable perception - a model-based fMRI study.
AB - In bistable vision, subjective perception wavers between two interpretations of a
constant ambiguous stimulus. This dissociation between conscious perception and
sensory stimulation has motivated various empirical studies on the neural
correlates of bistable perception, but the neurocomputational mechanism behind
endogenous perceptual transitions has remained elusive. Here, we recurred to a
generic Bayesian framework of predictive coding and devised a model that casts
endogenous perceptual transitions as a consequence of prediction errors emerging
from residual evidence for the suppressed percept. Data simulations revealed
close similarities between the model's predictions and key temporal
characteristics of perceptual bistability, indicating that the model was able to
reproduce bistable perception. Fitting the predictive coding model to behavioural
data from an fMRI-experiment on bistable perception, we found a correlation
across participants between the model parameter encoding perceptual stabilization
and the behaviourally measured frequency of perceptual transitions, corroborating
that the model successfully accounted for participants' perception. Formal model
comparison with established models of bistable perception based on mutual
inhibition and adaptation, noise or a combination of adaptation and noise was
used for the validation of the predictive coding model against the established
models. Most importantly, model-based analyses of the fMRI data revealed that
prediction error time-courses derived from the predictive coding model correlated
with neural signal time-courses in bilateral inferior frontal gyri and anterior
insulae. Voxel-wise model selection indicated a superiority of the predictive
coding model over conventional analysis approaches in explaining neural activity
in these frontal areas, suggesting that frontal cortex encodes prediction errors
that mediate endogenous perceptual transitions in bistable perception. Taken
together, our current work provides a theoretical framework that allows for the
analysis of behavioural and neural data using a predictive coding perspective on
bistable perception. In this, our approach posits a crucial role of prediction
error signalling for the resolution of perceptual ambiguities.
PMID- 28505153
TI - Gene duplication and co-evolution of G1/S transcription factor specificity in
fungi are essential for optimizing cell fitness.
AB - Transcriptional regulatory networks play a central role in optimizing cell
survival. How DNA binding domains and cis-regulatory DNA binding sequences have
co-evolved to allow the expansion of transcriptional networks and how this
contributes to cellular fitness remains unclear. Here we experimentally explore
how the complex G1/S transcriptional network evolved in the budding yeast
Saccharomyces cerevisiae by examining different chimeric transcription factor
(TF) complexes. Over 200 G1/S genes are regulated by either one of the two TF
complexes, SBF and MBF, which bind to specific DNA binding sequences, SCB and
MCB, respectively. The difference in size and complexity of the G1/S
transcriptional network across yeast species makes it well suited to investigate
how TF paralogs (SBF and MBF) and DNA binding sequences (SCB and MCB) co-evolved
after gene duplication to rewire and expand the network of G1/S target genes. Our
data suggests that whilst SBF is the likely ancestral regulatory complex, the
ancestral DNA binding element is more MCB-like. G1/S network expansion took place
by both cis- and trans- co-evolutionary changes in closely related but distinct
regulatory sequences. Replacement of the endogenous SBF DNA-binding domain (DBD)
with that from more distantly related fungi leads to a contraction of the SBF
regulated G1/S network in budding yeast, which also correlates with increased
defects in cell growth, cell size, and proliferation.
PMID- 28505154
TI - Dissecting the human serum antibody response to secondary dengue virus
infections.
AB - Dengue viruses (DENVs) are mosquito-borne flaviviruses and the causative agents
of dengue fever and dengue hemorrhagic fever. As there are four serotypes of DENV
(DENV1-4), people can be infected multiple times, each time with a new serotype.
Primary infections stimulate antibodies that mainly neutralize the serotype of
infection (type-specific), whereas secondary infections stimulate responses that
cross-neutralize 2 or more serotypes. Previous studies have demonstrated that
neutralizing antibodies induced by primary infections recognize tertiary and
quaternary structure epitopes on the viral envelope (E) protein that are unique
to each serotype. The goal of the current study was to determine the properties
of neutralizing antibodies induced after secondary infection with a different
(heterotypic) DENV serotypes. We evaluated whether polyclonal neutralizing
antibody responses after secondary infections consist of distinct populations of
type-specific antibodies to each serotype encountered or a new population of
broadly cross-neutralizing antibodies. We observed two types of responses: in
some individuals exposed to secondary infections, DENV neutralization was
dominated by cross-reactive antibodies, whereas in other individuals both type
specific and cross-reactive antibodies contributed to neutralization. To better
understand the origins of type-specific and cross-reactive neutralizing
antibodies, we analyzed sera from individuals with well-documented sequential
infections with two DENV serotypes only. These individuals had both type-specific
and cross-reactive neutralizing antibodies to the 2 serotypes responsible for
infection and only cross-reactive neutralizing antibodies to other serotypes.
Collectively, the results demonstrate that the quality of neutralizing (and
presumably protective) antibodies are different in individuals depending on the
number of previous exposures to different DENV serotypes. We propose a model in
which low affinity, cross-reactive antibody secreting B-cell clones induced by
primary exposure evolve during each secondary infection to secrete higher
affinity and more broadly neutralizing antibodies.
PMID- 28505155
TI - Oxidative stress and expression of insulin signaling proteins in the brain of
diabetic rats: Role of Nigella sativa oil and antidiabetic drugs.
AB - BACKGROUND AND OBJECTIVES: Insulin resistance of the brain is a specific form of
type2-diabetes mellitus (T2DM) and the active insulin-signaling pathway plays a
neuroprotective role against damaging conditions and Alzheimer's progression. The
present study identifies the mediated emerging effects of the Nigella sativa oil
(NSO) on the memory enhancing process, its anti-oxidative, acetylcholinestrase
(AChE) inhibition, anti-brain insulin resistance and anti-amyloidogenic
activities. In addition, the possible role of some anti-diabetic drugs in the
neuro-protection processes and their effect in combination with NSO and/or the
insulin receptor inhibitor IOMe-AG538 were investigated. METHODS: T2DM-induced
rats were orally and daily administrated 2.0 ml NSO, 100 mg metformin (MT), 0.8
mg glimepiride (GI) and different combinations (100 mg MT & 2.0 ml NSO, 0.8 mg GI
& 2.0 ml NSO and 2.0 ml NSO & intraperitoneal injection of 1/100 LD50 of IOMe
AG538) per kg body weight for 21 days. RESULTS: A significant increase in the
brain lipid peroxidation and decrease in the antioxidant status with peripheral
and central production of pro-inflammatory mediators were observed in diabetes
induced rats. The brain AChE was activated and associated with diminished brain
glucose level and cholinergic function. In addition, the brain insulin resistance
and the attenuated insulin signaling pathway (p-IRS/ p-AKT/p-GSK-3beta) were
accompanied by an augmentation in GSK-3beta level, which in turn may contribute
in the extensive alterations of Tau phosphorylation along with changes in PP2A
level. Furthermore, neuronal loss and elevation in Abeta-42 plaque formation were
observed due to a low IDE formation and an increased expression of p53, BACE1 and
APP with diminished ADAM10, SIRT1 and BDNF levels. The expression profile of AD
related miRNAs in sera and brain tissues displayed its neuro-protection role. The
treatment of diabetes-induced rats with NSO and the anti-diabetic drugs alone
and/or in combination have the potential to suppress the oxidative stress, the
pro-inflammatory mediators and amyloidogenic pathway. Moreover, it lowers the
insulin receptor inhibitory effect of IOMe-AG538 and modifies the insulin
signaling pathway. Therefore, it prevents the neurotoxicity, amyloid plaque
formation and Tau hyper-phosphorylation and restores AD-related miRNA normal
levels. CONCLUSION: These data suggest that NSO or its combined treatments with
anti-diabetic drugs have a possible benefit as disease modifying agents for the
insulin resistance in the brain through enhancing brain insulin signaling
pathway.
PMID- 28505156
TI - An independent component analysis confounding factor correction framework for
identifying broad impact expression quantitative trait loci.
AB - Genome-wide expression Quantitative Trait Loci (eQTL) studies in humans have
provided numerous insights into the genetics of both gene expression and complex
diseases. While the majority of eQTL identified in genome-wide analyses impact a
single gene, eQTL that impact many genes are particularly valuable for network
modeling and disease analysis. To enable the identification of such broad impact
eQTL, we introduce CONFETI: Confounding Factor Estimation Through Independent
component analysis. CONFETI is designed to address two conflicting issues when
searching for broad impact eQTL: the need to account for non-genetic confounding
factors that can lower the power of the analysis or produce broad impact eQTL
false positives, and the tendency of methods that account for confounding factors
to model broad impact eQTL as non-genetic variation. The key advance of the
CONFETI framework is the use of Independent Component Analysis (ICA) to identify
variation likely caused by broad impact eQTL when constructing the sample
covariance matrix used for the random effect in a mixed model. We show that
CONFETI has better performance than other mixed model confounding factor methods
when considering broad impact eQTL recovery from synthetic data. We also used the
CONFETI framework and these same confounding factor methods to identify eQTL that
replicate between matched twin pair datasets in the Multiple Tissue Human
Expression Resource (MuTHER), the Depression Genes Networks study (DGN), the
Netherlands Study of Depression and Anxiety (NESDA), and multiple tissue types in
the Genotype-Tissue Expression (GTEx) consortium. These analyses identified both
cis-eQTL and trans-eQTL impacting individual genes, and CONFETI had better or
comparable performance to other mixed model confounding factor analysis methods
when identifying such eQTL. In these analyses, we were able to identify and
replicate a few broad impact eQTL although the overall number was small even when
applying CONFETI. In light of these results, we discuss the broad impact eQTL
that have been previously reported from the analysis of human data and suggest
that considerable caution should be exercised when making biological inferences
based on these reported eQTL.
PMID- 28505157
TI - Structurally optimized analogs of the retrograde trafficking inhibitor Retro
2cycl limit Leishmania infections.
AB - In infected mammalian cells, Leishmania parasites reside within specialized
compartments called parasitophorous vacuoles (LPVs). We have previously shown
that Retro-2, a member of a novel class of small retrograde pathway inhibitors
caused reduced LPV sizes and lower parasite numbers during experimental L.
mexicana sp. infections. The purpose of this study was to determine if structural
analogs of Retro-2cycl reported to have superior potency in the inhibition of
retrograde pathway-dependent phenomena (i.e., polyomavirus cellular infection by
polyomavrius and Shiga toxin trafficking in cells) are also more effective than
the parent compound at controlling Leishmania infections. In addition to their
effects on LPV development, we show that two optimized analogs of Retro-2cycl,
DHQZ 36 and DHQZ 36.1 limit Leishmania amazonensis infection in macrophages at
EC50 of 13.63+/-2.58MUM and10.57+/-2.66MUM, respectively, which is significantly
lower than 40.15MUM the EC50 of Retro-2cycl. In addition, these analogs caused a
reversal in Leishmania induced suppression of IL-6 release by infected cells
after LPS activation. Moreover, we show that in contrast to Retro-2cycl that is
Leishmania static, the analogs can kill Leishmania parasites in axenic cultures,
which is a desirable attribute for any drug to treat Leishmania infections.
Together, these studies validate and extend the published structure-activity
relationship analyses of Retro-2cycl.
PMID- 28505158
TI - Investigation of the effect of cochlear implant electrode length on speech
comprehension in quiet and noise compared with the results with users of electro
acoustic-stimulation, a retrospective analysis.
AB - OBJECTIVES: This investigation evaluated the effect of cochlear implant (CI)
electrode length on speech comprehension in quiet and noise and compare the
results with those of EAS users. METHODES: 91 adults with some degree of residual
hearing were implanted with a FLEX20, FLEX24, or FLEX28 electrode. Some subjects
were postoperative electric-acoustic-stimulation (EAS) users; the other subjects
were in the groups of electric stimulation-only (ES-only). Speech perception was
tested in quiet and noise at 3 and 6 months of ES or EAS use. Speech
comprehension results were analyzed and correlated to electrode length. RESULTS:
While the FLEX20 ES and FLEX24 ES groups were still in their learning phase
between the 3 to 6 months interval, the FLEX28 ES group was already reaching a
performance plateau at the three months appointment yielding remarkably high test
scores. EAS subjects using FLEX20 or FLEX24 electrodes outscored ES-only subjects
with the same short electrodes on all 3 tests at each interval, reaching
significance with FLEX20 ES and FLEX24 ES subjects on all 3 tests at the 3-months
interval and on 2 tests at the 6- months interval. Amongst ES-only subjects at
the 3- months interval, FLEX28 ES subjects significantly outscored FLEX20 ES
subjects on all 3 tests and the FLEX24 ES subjects on 2 tests. At the-6 months
interval, FLEX28 ES subjects still exceeded the other ES-only subjects although
the difference did not reach significance. CONCLUSIONS: Among ES-only users, the
FLEX28 ES users had the best speech comprehension scores, at the 3- months
appointment and tendentially at the 6 months appointment. EAS users showed
significantly better speech comprehension results compared to ES-only users with
the same short electrodes.
PMID- 28505159
TI - Infectious disease ward admission positively influences P. jiroveci pneumonia
(PjP) outcome: A retrospective analysis of 116 HIV-positive and HIV-negative
immunocompromised patients.
AB - P. jiroveci (Pj) causes a potentially fatal pneumonia in immunocompromised
patients and the factors associated with a bad outcome are poorly understood. A
retrospective analysis on Pj pneumonia (PjP) cases occurring in Tor Vergata
University Hospital, Italy, during the period 2011-2015. The patients'
demographic, clinical and radiological characteristics and the Pj genotypes were
considered. The study population included 116 patients, 37.9% of whom had
haematological malignancy or underwent haematological stem cell transplantation
(HSCT), 22.4% had HIV infection, 16.4% had chronic lung diseases (CLD), 7.8% had
a solid cancer, and 3.4% underwent a solid organ transplant (SOT). The remaining
12.1% had a miscellaneous other condition. At univariate analysis, being older
than 60 years was significantly correlated with a severe PjP (OR [95%CI] 2.52
[0.10-5.76]; p = 0.031) and death (OR [95%CI] 2.44 [1.05-5.70]; p = 0.036), while
a previous trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis were significantly
associated with a less severe pneumonia (OR[95%CI] 0.35 [0.15-0.84], p = 0.023);
moreover, death due to PjP was significantly more frequent in patients with CLD
(OR[95%CI] 3.26 [1.17-9.05]; p = 0.019) while, admission to the Infectious
Diseases Unit was significantly associated with fewer deaths (OR[95%CI] 0.10
[0.03-0.36], p = 0.002). At multivariate analysis, a better PjP outcome was
observed in patients taking TMP/SMX prophylaxis and that were admitted to the
Infectious Diseases Unit (OR[95%CI] 0.27 [0.07-1.03], p = 0.055, OR[95%CI] 0.16
[0.05-0.55]; p = 0.004, respectively). In conclusion, in our study population,
TMP/SMX prophylaxis and infectious disease specialist approach were variables
correlated with a better PjP outcome.
PMID- 28505161
TI - Effect on healthcare utilization and costs of spinal manual therapy for acute low
back pain in routine care: A propensity score matched cohort study.
AB - Spinal manual therapy (SMT) is a popular treatment option for low back pain
(LBP). The aim of our analysis was to evaluate the effects of manual therapy
delivered by general practitioners and ambulatory orthopedic surgeons in routine
care on follow up consultations, sick leave, health service utilization and costs
for acute LBP compared to matched patients not receiving manual therapy. This is
a propensity score matched cohort study based on health claims data. We
identified a total of 113.652 adult patients with acute LBP and no coded red
flags of whom 21.021 (18%) received SMT by physicians. In the final analysis
17.965 patients in each group could be matched. Balance on patients' coded
characteristics, comorbidity and prior health service utilization was achieved.
The provision of SMT for acute LBP had no relevant impact on follow up visits and
days of sick leave for LBP in the index billing period and the following year.
SMT was associated with a higher proportion of imaging studies for LBP (30.6% vs.
23%, SMD: 0.164 [95% CI 0.143-0.185]). SMT did not lead to meaningful savings by
replacing other health services for LBP. SMT for acute non-specific LBP in
routine care was not clinically meaningful effective to reduce sick leave and
reconsultation rates compared to no SMT and did not lead to meaningful savings by
replacing other health services from the perspective of health insurance. This
does not imply that SMT is ineffective but might reflect a problem with selection
of suitable patients and the quality and quantity of SMT in routine care.
National Manual Medicine societies should state clearly that imaging is not
routinely needed prior to SMT in patients with low suspicion of presence of red
flags and monitor the quality of provided services.
PMID- 28505160
TI - Role of NF-E2 related factor 2 (Nrf2) on chemotherapy resistance in acute myeloid
leukemia (AML) and the effect of pharmacological inhibition of Nrf2.
AB - Cytarabine (Ara-C) and Daunorubicin (Dnr) forms the backbone of acute myeloid
leukemia (AML) therapy. Drug resistance and toxic side effects pose a major
threat to treatment success and hence alternate less toxic therapies are
warranted. NF-E2 related factor-2 (Nrf2), a master regulator of antioxidant
response is implicated in chemoresistance in solid tumors. However, little is
known about the role of Nrf2 in AML chemoresistance and the effect of
pharmacological inhibitor brusatol in modulating this resistance. Primary AML
samples with high ex-vivo IC50 to Ara-C, ATO, Dnr had significantly high NRF2 RNA
expression. Gene-specific knockdown of NRF2 improved sensitivity to these drugs
in resistant AML cell lines by decreasing the expression of downstream
antioxidant targets of Nrf2 by compromising the cell's ability to scavenge the
ROS. Treatment with brusatol, a pharmacological inhibitor of Nrf2, improved
sensitivity to Ara-C, ATO, and Dnr and reduced colony formation capacity. AML
cell lines stably overexpressing NRF2 showed increased resistance to ATO, Dnr and
Ara-C and increased expression of downstream targets. This study demonstrates
that Nrf2 could be an ideal druggable target in AML, more so to the drugs that
function through ROS, suggesting the possibility of using Nrf2 inhibitors in
combination with chemotherapeutic agents to modulate drug resistance in AML.
PMID- 28505162
TI - Gender differences in the transmission of risk for antisocial behavior problems
across generations.
AB - Previous studies have shown that children of alcohol use disorder (AUD) parents
are more likely to develop alcohol problems as well as antisocial and other
behavior problems. The purpose of this study was to examine gender discordance in
the effect of early maternal and paternal influences on antisocial behaviors of
boys and girls, as well as the environmental factors that moderate the parental
effects. Specifically, we examined the effects of childhood and adulthood
antisocial behavior of the parents on offspring antisocial behavior as young
adults. We also examined whether mothers' and fathers' drinking problems when
offspring were young children (6-8 years) affected offspring antisocial behavior
as young adults (18-21 years). We evaluated 655 children from 339 families in the
Michigan Longitudinal Study (MLS), a prospective study of AUD and non-AUD
families. Path models were constructed in order to test for the parental
contributions to offspring outcomes. We found that both mothers' and fathers'
antisocial behavior contributed to the children's young adult antisocial
behavior. Only mothers' drinking problems while their children were little had a
significant effect on their sons' later drinking, but not on their daughters'.
These different parental effects suggest that maternal and paternal influences
may be mediated by different mechanisms.
PMID- 28505165
TI - Determination of fruit maturity and its prediction model based on the pericarp
index of absorbance difference (IAD) for peaches.
AB - Harvest maturity is closely related to peach fruit quality and has a very
important effect on the fresh fruit market. Unfortunately, at present, it is
difficult to determine the maturity level of peach fruits by artificial methods.
The objectives of this study were to develop quadratic polynomial regression
models using near-infrared spectroscopy that could determine the peel color
difference, fruit firmness, soluble solids content (SSC), soluble sugar, organic
acid components, and their relationships with the absorbance of chlorophyll
(index of absorbance difference, IAD) in late maturing 'Xiahui 8' peach and
'Xiaguang' nectarine fruits. The analysis was based on data for fruits at
veraison, fruits at harvesting maturity, and all fruits. The results showed that
firmness has the highest correlation coefficient with IAD. Prediction models for
fruit maturity were established between firmness and the IAD of the two cultivars
using the quadratic polynomial regression method. Further variance analysis on
the one degree term and quadratic term of each equation showed that every partial
regression coefficient reached a significant or extremely significant level. No
significant difference was observed between estimated and observed values after
regression prediction. The regression equations seem to fit well. Other peach and
nectarine varieties were used to test the feasibility of maturity prediction by
this method, and it was found that maturity was successfully predicted in all the
samples. The result indicated that the IAD can be used as an index to predict
peach fruit maturity.
PMID- 28505163
TI - Anti-citrullinated peptide antibodies are the strongest predictor of clinically
relevant radiographic progression in rheumatoid arthritis patients achieving
remission or low disease activity: A post hoc analysis of a nationwide cohort in
Japan.
AB - OBJECTIVES: To determine prognostic factors of clinically relevant radiographic
progression (CRRP) in patients with rheumatoid arthritis (RA) achieving remission
or low disease activity (LDA) in clinical practice. METHODS: Using data from a
nationwide, multicenter, prospective study in Japan, we evaluated 198 biological
disease-modifying antirheumatic drug (bDMARD)-naive RA patients who were in
remission or had LDA at study entry after being treated with conventional
synthetic DMARDs (csDMARDs). CRRP was defined as the yearly progression of
modified total Sharp score (mTSS) >3.0 U. We performed a multiple logistic
regression analysis to explore the factors to predict CRRP at 1 year. We used
receiver operating characteristic (ROC) curve to estimate the performance of
relevant variables for predicting CRRP. RESULTS: The mean Disease Activity Score
in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) was 2.32 +/- 0.58 at
study entry. During the 1-year observation, remission or LDA persisted in 72% of
the patients. CRRP was observed in 7.6% of the patients. The multiple logistic
regression analysis revealed that the independent variables to predict the
development of CRRP were: anti-citrullinated peptide antibodies (ACPA) positivity
at baseline (OR = 15.2, 95%CI 2.64-299), time-integrated DAS28-ESR during the 1
year post-baseline (7.85-unit increase, OR = 1.83, 95%CI 1.03-3.45), and the mTSS
at baseline (13-unit increase, OR = 1.22, 95%CI 1.06-1.42). CONCLUSIONS: ACPA
positivity was the strongest independent predictor of CRRP in patients with RA in
remission or LDA. Physicians should recognize ACPA as a poor-prognosis factor
regarding the radiographic outcome of RA, even among patients showing a
clinically favorable response to DMARDs.
PMID- 28505164
TI - Human decellularized bone scaffolds from aged donors show improved osteoinductive
capacity compared to young donor bone.
AB - To improve the safe use of allograft bone, decellularization techniques may be
utilized to produce acellular scaffolds. Such scaffolds should retain their
innate biological and biomechanical capacity and support mesenchymal stem cell
(MSC) osteogenic differentiation. However, as allograft bone is derived from a
wide age-range, this study aimed to determine whether donor age impacts on the
ability an osteoinductive, acellular scaffold produced from human bone to promote
the osteogenic differentiation of bone marrow MSCs (BM-MSC). BM-MSCs from young
and old donors were seeded on acellular bone cubes from young and old donors
undergoing osteoarthritis related hip surgery. All combinations resulted in
increased osteogenic gene expression, and alkaline phosphatase (ALP) enzyme
activity, however BM-MSCs cultured on old donor bone displayed the largest
increases. BM-MSCs cultured in old donor bone conditioned media also displayed
higher osteogenic gene expression and ALP activity than those exposed to young
donor bone conditioned media. ELISA and Luminex analysis of conditioned media
demonstrated similar levels of bioactive factors between age groups; however, IGF
binding protein 1 (IGFBP1) concentration was significantly higher in young donor
samples. Additionally, structural analysis of old donor bone indicated an
increased porosity compared to young donor bone. These results demonstrate the
ability of a decellularized scaffold produced from young and old donors to
support osteogenic differentiation of cells from young and old donors.
Significantly, the older donor bone produced greater osteogenic differentiation
which may be related to reduced IGFBP1 bioavailability and increased porosity,
potentially explaining the excellent clinical results seen with the use of
allograft from aged donors.
PMID- 28505166
TI - Brain activation of semantic category-based grouping in multiple identity
tracking task.
AB - Using Multiple Identity Tracking task and the functional magnetic resonance
imaging (fMRI) technology, the present study aimed to isolate and visualize the
functional anatomy of neural systems involved in the semantic category-based
grouping process. Three experiment conditions were selected and compared: the
category-based targets grouping (TG) condition, the targets-distractors grouping
(TDG) condition and the homogenous condition. In the TG condition, observers
could utilize the categorical distinction between targets and distractors, to
construct a uniform presentation of targets, that is, to form a group of the
targets to facilitate tracking. In the TDG condition, half the targets and half
the distractors belonged to the same category. Observers had to inhibit the
grouping of targets and distractors in one category to complete tracking. In the
homogenous condition, where targets and distractors consisted of the same
objects, no grouping could be formed. The "TG-Homogenous" contrast (p<0.01)
revealed the activation of the left fusiform and the pars triangularis of
inferior frontal gyrus (IFG). The "TG-TDG" contrast only revealed the activation
of the left anterior cingulate gyrus (ACC). The fusiform and IFG pars
triangularis might participate in the representation of semantic knowledge, IFG
pars triangularis might relate intensely with the classification of semantic
categories. The ACC might be responsible for the initiation and maintenance of
grouping representation.
PMID- 28505168
TI - Development and validation of reversed-phase HPLC gradient method for the
estimation of efavirenz in plasma.
AB - Efavirenz is an anti-viral agent of non-nucleoside reverse transcriptase
inhibitor category used as a part of highly active retroviral therapy for the
treatment of infections of human immune deficiency virus type-1. A simple,
sensitive and rapid reversed-phase high performance liquid chromatographic
gradient method was developed and validated for the determination of efavirenz in
plasma. The method was developed with high performance liquid chromatography
using Waters X-Terra Shield, RP18 50 x 4.6 mm, 3.5 MUm column and a mobile phase
consisting of phosphate buffer pH 3.5 and Acetonitrile. The elute was monitored
with the UV-Visible detector at 260 nm with a flow rate of 1.5 mL/min. Tenofovir
disoproxil fumarate was used as internal standard. The method was validated for
linearity, precision, accuracy, specificity, robustness and data obtained were
statistically analyzed. Calibration curve was found to be linear over the
concentration range of 1-300 MUg/mL. The retention times of efavirenz and
tenofovir disoproxil fumarate (internal standard) were 5.941 min and 4.356 min
respectively. The regression coefficient value was found to be 0.999. The limit
of detection and the limit of quantification obtained were 0.03 and 0.1 MUg/mL
respectively. The developed HPLC method can be useful for quantitative
pharmacokinetic parameters determination of efavirenz in plasma.
PMID- 28505167
TI - Relationship of hyperlipidemia to comorbidities and lung function in COPD:
Results of the COSYCONET cohort.
AB - Although hyperlipidemia is common in COPD, its relationship to comorbidities,
risk factors and lung function in COPD has not been studied in detail. Using the
baseline data of the COSYCONET cohort we addressed this question. Data from 1746
COPD patients (GOLD stage 1-4; mean age 64.6 y, mean FEV1%pred 57%) were
evaluated, focusing on the comorbidities hyperlipidemia, diabetes and
cardiovascular complex (CVC; including arterial hypertension, cardiac failure,
ischemic heart disease). Risk factors comprised age, gender, BMI, and packyears
of smoking. The results of linear and logistic regression analyses were
implemented into a path analysis model describing the multiple relationships
between parameters. Hyperlipidemia (prevalence 42.9%) was associated with lower
intrathoracic gas volume (ITGV) and higher forced expiratory volume in 1 second
(FEV1) when adjusting for its multiple relationships to risk factors and other
comorbidities. These findings were robust in various statistical analyses. The
associations between comorbidities and risk factors were in accordance with
previous findings, thereby underlining the validity of our data. In conclusion,
hyperlipidemia was associated with less hyperinflation and airway obstruction in
patients with COPD. This surprising result might be due to different COPD
phenotypes in these patients or related to effects of medication.
PMID- 28505169
TI - Molecular basis of targeted therapy in T/NK-cell lymphoma/leukemia: A
comprehensive genomic and immunohistochemical analysis of a panel of 33 cell
lines.
AB - T and NK-cell lymphoma is a collection of aggressive disorders with unfavorable
outcome, in which targeted treatments are still at a preliminary phase. To gain
deeper insights into the deregulated mechanisms promoting this disease, we
searched a panel of 31 representative T-cell and 2 NK-cell lymphoma/leukemia cell
lines for predictive markers of response to targeted therapy. To this end,
targeted sequencing was performed alongside the expression of specific biomarkers
corresponding to potentially activated survival pathways. The study identified
TP53, NOTCH1 and DNMT3A as the most frequently mutated genes. We also found
common alterations in JAK/STAT and epigenetic pathways. Immunohistochemical
analysis showed nuclear accumulation of MYC (in 85% of the cases), NFKB (62%), p
STAT (44%) and p-MAPK (30%). This panel of cell lines captures the complexity of
T/NK-cell lymphoproliferative processes samples, with the partial exception of
AITL cases. Integrated mutational and immunohistochemical analysis shows that
mutational changes cannot fully explain the activation of key survival pathways
and the resulting phenotypes. The combined integration of mutational/expression
changes forms a useful tool with which new compounds may be assayed.
PMID- 28505170
TI - IFN-gamma fails to overcome inhibition of selected macrophage activation events
in response to pathogenic mycobacteria.
AB - According to most models of mycobacterial infection, inhibition of the pro
inflammatory macrophage immune responses contributes to the persistence of
bacteria. Mycobacterium avium subsp. paratuberculosis (MAP) is a highly
successful pathogen in cattle and sheep and is also implicated as the causative
agent of Crohn's disease in humans. Pathogenic mycobacteria such as MAP have
developed multiple strategies to evade host defence mechanisms including
interfering with the macrophages' capacity to respond to IFN-gamma, a feature
which might be lacking in non-pathogenic mycobacteria such as M. smegmatis. We
hypothesized that pre-sensitisation of macrophages with the pro-inflammatory
cytokine IFN-gamma would help in overcoming the inhibitory effect of MAP or its
antigens on macrophage inflammatory responses. Herein we have compared a series
of macrophage activation parameters in response to MAP and M. smegmatis as well
as mycobacterial antigens. While IFN-gamma did overcome the inhibition in immune
suppressive mechanisms in response to MAP antigen as well as M. smegmatis, we
could not find a clear role for IFN-gamma in overcoming the inhibition of
macrophage inflammatory responses to the pathogenic mycobacterium, MAP. We
demonstrate that suppression of macrophage defence mechanisms by pathogenic
mycobacteria is unlikely to be overcome by prior sensitization with IFN-gamma
alone. This indicates that IFN-gamma signaling pathway-independent mechanisms may
exist for overcoming inhibition of macrophage effector functions in response to
pathogenic mycobacteria. These findings have important implications in
understanding the survival mechanisms of pathogenic mycobacteria directed towards
finding better therapeutics and vaccination strategies.
PMID- 28505171
TI - Rapid deployment of a mobile biosafety level-3 laboratory in Sierra Leone during
the 2014 Ebola virus epidemic.
AB - BACKGROUND: Ebola virus emerged in West Africa in December 2013. The high
population mobility and poor public health infrastructure in this region led to
the development of the largest Ebola virus disease (EVD) outbreak to date.
METHODOLOGY/PRINCIPAL FINDINGS: On September 26, 2014, China dispatched a Mobile
Biosafety Level-3 Laboratory (MBSL-3 Lab) and a well-trained diagnostic team to
Sierra Leone to assist in EVD diagnosis using quantitative real-time PCR, which
allowed the diagnosis of suspected EVD cases in less than 4 hours from the time
of sample receiving. This laboratory was composed of three container vehicles
equipped with advanced ventilation system, communication system, electricity and
gas supply system. We strictly applied multiple safety precautions to reduce
exposure risks. Personnel, materials, water and air flow management were the key
elements of the biosafety measures in the MBSL-3 Lab. Air samples were regularly
collected from the MBSL-3 Lab, but no evidence of Ebola virus infectious aerosols
was detected. Potentially contaminated objects were also tested by collecting
swabs. On one occasion, a pipette tested positive for EVD. A total of 1,635
suspected EVD cases (824 positive [50.4%]) were tested from September 28 to
November 11, 2014, and no member of the diagnostic team was infected with Ebola
virus or other pathogens, including Lassa fever. The specimens tested included
blood (69.2%) and oral swabs (30.8%) with positivity rates of 54.2% and 41.9%,
respectively. The China mobile laboratory was thus instrumental in the EVD
outbreak response by providing timely and reliable diagnostics.
CONCLUSIONS/SIGNIFICANCE: The MBSL-3 Lab significantly contributed to
establishing a suitable laboratory response capacity during the emergence of EVD
in Sierra Leone.
PMID- 28505172
TI - Increased nucleoside diphosphate kinase activity induces white spot syndrome
virus infection in Litopenaeus vannamei.
AB - Nucleoside diphosphate kinase (NDK), which has the same sequence as oncoprotein
(OP) in humans, can induce nucleoside triphosphates in DNA replication by
maintenance of the deoxynucleotide triphosphate (dNTP's) and is known to be
regulated by viral infection in the shrimp Litopenaeus vannamei. This paper
describes the relationship between NDK and white spot syndrome virus (WSSV)
infection. The recombinant NDK was produced by a prokaryotic expression system.
WSSV copy numbers and mRNA levels of IE1 and VP28 were significantly increased in
shrimp injected with recombinant NDK at 72 h after WSSV infection. After
synthesizing dsRNA-NDK and confirming the efficacy of NDK silencing, we recorded
the cumulative mortality of WSSV-infected shrimp injected with NDK and dsRNA-NDK.
A comparison between the results demonstrated that silencing NDK delayed the
death of shrimps. These findings indicate that NDK has an important role
influencing the replication of WSSV replication in shrimp. Furthermore, NDK may
have potential target as a new therapeutic strategy against WSSV infection in
shrimp.
PMID- 28505173
TI - Continental divide: Predicting climate-mediated fragmentation and biodiversity
loss in the boreal forest.
AB - Climate change threatens natural landscapes through shifting distribution and
abundance of species and attendant change in the structure and function of
ecosystems. However, it remains unclear how climate-mediated variation in
species' environmental niche space may lead to large-scale fragmentation of
species distributions, altered meta-population dynamics and gene flow, and
disrupted ecosystem integrity. Such change may be especially relevant when
species distributions are restricted either spatially or to a narrow
environmental niche, or when environments are rapidly changing. Here, we use
range-wide environmental niche models to posit that climate-mediated range
fragmentation aggravates the direct effects of climate change on species in the
boreal forest of North America. We show that climate change will directly alter
environmental niche suitability for boreal-obligate species of trees, birds and
mammals (n = 12), with most species ranges becoming smaller and shifting
northward through time. Importantly, species distributions will become
increasingly fragmented, as characterized by smaller mean size and greater
isolation of environmentally-suitable landscape patches. This loss is especially
pronounced along the Ontario-Quebec border, where the boreal forest is narrowest
and roughly 78% of suitable niche space could disappear by 2080. Despite the
diversity of taxa surveyed, patterns of range fragmentation are remarkably
consistent, with our models predicting that spruce grouse (Dendragapus
canadensis), boreal chickadee (Poecile hudsonicus), moose (Alces americanus) and
caribou (Rangifer tarandus) could have entirely disjunct east-west population
segments in North America. These findings reveal potentially dire consequences of
climate change on population continuity and species diversity in the boreal
forest, highlighting the need to better understand: 1) extent and primary drivers
of anticipated climate-mediated range loss and fragmentation; 2) diversity of
species to be affected by such change; 3) potential for rapid adaptation in the
most strongly-affected areas; and 4) potential for invasion by replacement
species.
PMID- 28505175
TI - Structural insights into reptarenavirus cap-snatching machinery.
AB - Cap-snatching was first discovered in influenza virus. Structures of the involved
domains of the influenza virus polymerase, namely the endonuclease in the PA
subunit and the cap-binding domain in the PB2 subunit, have been solved. Cap
snatching endonucleases have also been demonstrated at the very N-terminus of the
L proteins of mammarena-, orthobunya-, and hantaviruses. However, a cap-binding
domain has not been identified in an arena- or bunyavirus L protein so far. We
solved the structure of the 326 C-terminal residues of the L protein of
California Academy of Sciences virus (CASV), a reptarenavirus, by X-ray
crystallography. The individual domains of this 37-kDa fragment (L-Cterm) as well
as the domain arrangement are structurally similar to the cap-binding and
adjacent domains of influenza virus polymerase PB2 subunit, despite the absence
of sequence homology, suggesting a common evolutionary origin. This enabled
identification of a region in CASV L-Cterm with similarity to a cap-binding site;
however, the typical sandwich of two aromatic residues was missing. Consistent
with this, cap-binding to CASV L-Cterm could not be detected biochemically. In
addition, we solved the crystal structure of the corresponding endonuclease in
the N-terminus of CASV L protein. It shows a typical endonuclease fold with an
active site configuration that is essentially identical to that of known
mammarenavirus endonuclease structures. In conclusion, we provide evidence for a
presumably functional cap-snatching endonuclease in the N-terminus and a
degenerate cap-binding domain in the C-terminus of a reptarenavirus L protein.
Implications of these findings for the cap-snatching mechanism in arenaviruses
are discussed.
PMID- 28505174
TI - Extracellular matrix nitration alters growth factor release and activates
bioactive complement in human retinal pigment epithelial cells.
AB - PURPOSE: We have shown previously that non-enzymatic nitration (NEN) of the
extracellular matrix (ECM), which serves as a model of Bruch's membrane (BM)
aging, has a profound effect on the behavior of the overlying retinal pigment
epithelial (RPE) cells, including altered phagocytic ability, reduced cell
adhesion, and inhibition of proliferation. We know that transplanted RPE
monolayers will encounter a hostile sub-RPE environment, including age-related
alterations in BM that may compromise cell function and survival. Here we use our
previous NEN model of BM aging to determine the effects of NEN of the ECM on
growth factor release and complement activation in RPE cells. METHODS: Human
induced-pluripotent stem cells (iPSCs) were differentiated into RPE cells, and
confirmed by immunohistochemistry, confocal microscopy, and polymerase chain
reaction. IPSC-derived RPE cells were plated onto RPE-derived ECM under untreated
or nitrite-modified conditions. Cells were cultured for 7 days and barrier
function measured by transepithelial resistance (TER). Vascular endothelial
growth factor (VEGF), pigment epithelium-derived factor (PEDF), and complement
component C3a were measured using enzyme-linked immunosorbent assay (ELISA).
RESULTS: On average nitrite-modified ECM increased VEGF release both apically and
basally by 0.15 +/- 0.014 ng/mL (p <0.0001) and 0.21 +/- 0.022 ng/mL (p <0.0001),
respectively, in iPSC-derived RPE cells. Nitrite-modified ECM increased PEDF
release in iPSC-derived RPE cells apically by 0.16 +/- 0.031 ng/mL (p <0.0001),
but not basally (0.27 +/- 0.015 vs. 0.32 +/- 0.029 ng/mL, (p >0.05)). Nitrite
modified ECM increased production of C3a in iPSC-derived RPE cells by 0.52 +/-
0.123 ng/mL (p <0.05). CONCLUSION: Nitrite-modified ECM increased VEGF, PEDF
release, and C3a production in human iPSC-derived RPE cells. This model
demonstrates changes seen in the basement membrane can lead to alterations in the
cell biology of the RPE cells that may be related to the development of age
related macular degeneration.
PMID- 28505176
TI - Systematic, multiparametric analysis of Mycobacterium tuberculosis intracellular
infection offers insight into coordinated virulence.
AB - A key to the pathogenic success of Mycobacterium tuberculosis (Mtb), the
causative agent of tuberculosis, is the capacity to survive within host
macrophages. Although several factors required for this survival have been
identified, a comprehensive knowledge of such factors and how they work together
to manipulate the host environment to benefit bacterial survival are not well
understood. To systematically identify Mtb factors required for intracellular
growth, we screened an arrayed, non-redundant Mtb transposon mutant library by
high-content imaging to characterize the mutant-macrophage interaction. Based on
a combination of imaging features, we identified mutants impaired for
intracellular survival. We then characterized the phenotype of infection with
each mutant by profiling the induced macrophage cytokine response. Taking a
systems-level approach to understanding the biology of identified mutants, we
performed a multiparametric analysis combining pathogen and host phenotypes to
predict functional relationships between mutants based on clustering. Strikingly,
mutants defective in two well-known virulence factors, the ESX-1 protein
secretion system and the virulence lipid phthiocerol dimycocerosate (PDIM),
clustered together. Building upon the shared phenotype of loss of the macrophage
type I interferon (IFN) response to infection, we found that PDIM production and
export are required for coordinated secretion of ESX-1-substrates, for phagosomal
permeabilization, and for downstream induction of the type I IFN response.
Multiparametric clustering also identified two novel genes that are required for
PDIM production and induction of the type I IFN response. Thus, multiparametric
analysis combining host and pathogen infection phenotypes can be used to identify
novel functional relationships between genes that play a role in infection.
PMID- 28505178
TI - A reverse dot blot assay for the screening of twenty mutations in four genes
associated with NSHL in a Chinese population.
AB - BACKGROUND: Congenital deafness is one of the most distressing disorders
affecting humanity and exhibits a high incidence worldwide. Most cases of
congenital deafness in the Chinese population are caused by defects in a limited
number of genes. A convenient and reliable method for detecting common deafness
related gene mutations in the Chinese population is required. METHODS: We
developed a PCR-reverse dot blot (RDB) assay for screening 20 hotspot mutations
of GJB2, GJB3, SLC26A4, and MT-RNR1, which are common non-syndromic hearing loss
(NSHL)-associated genes in the Chinese population. The PCR-RDB assay consists of
multiplex PCR amplifications of 10 fragments in the target sequence of the four
above-mentioned genes in wild-type and mutant genomic DNA samples followed by
hybridization to a test strip containing allele-specific oligonucleotide probes.
We applied our method to a set of 225 neonates with deafness gene mutations and
30 normal neonates. RESULTS: The test was validated through direct sequencing in
a blinded study with 100% concordance. CONCLUSIONS: The results demonstrated that
our reverse dot blot assay is a reliable and effective genetic screening method
for identifying carriers and individuals with NSHL among the Chinese population.
PMID- 28505177
TI - The clinico-radiological paradox of cognitive function and MRI burden of white
matter lesions in people with multiple sclerosis: A systematic review and meta
analysis.
AB - BACKGROUND: Moderate correlation exists between the imaging quantification of
brain white matter lesions and cognitive performance in people with multiple
sclerosis (MS). This may reflect the greater importance of other features,
including subvisible pathology, or methodological limitations of the primary
literature. OBJECTIVES: To summarise the cognitive clinico-radiological paradox
and explore the potential methodological factors that could influence the
assessment of this relationship. METHODS: Systematic review and meta-analysis of
primary research relating cognitive function to white matter lesion burden.
RESULTS: Fifty papers met eligibility criteria for review, and meta-analysis of
overall results was possible in thirty-two (2050 participants). Aggregate
correlation between cognition and T2 lesion burden was r = -0.30 (95% confidence
interval: -0.34, -0.26). Wide methodological variability was seen, particularly
related to key factors in the cognitive data capture and image analysis
techniques. CONCLUSIONS: Resolving the persistent clinico-radiological paradox
will likely require simultaneous evaluation of multiple components of the complex
pathology using optimum measurement techniques for both cognitive and MRI feature
quantification. We recommend a consensus initiative to support common standards
for image analysis in MS, enabling benchmarking while also supporting ongoing
innovation.
PMID- 28505179
TI - Food restriction increase the expression of mTORC1 complex genes in the skeletal
muscle of juvenile pacu (Piaractus mesopotamicus).
AB - Skeletal muscle is capable of phenotypic adaptation to environmental factors,
such as nutrient availability, by altering the balance between muscle catabolism
and anabolism that in turn coordinates muscle growth. Small noncoding RNAs, known
as microRNAs (miRNAs), repress the expression of target mRNAs, and many studies
have demonstrated that miRNAs regulate the mRNAs of catabolic and anabolic genes.
We evaluated muscle morphology, gene expression of components involved in
catabolism, anabolism and energetic metabolism and miRNAs expression in both the
fast and slow muscle of juvenile pacu (Piaractus mesopotamicus) during food
restriction and refeeding. Our analysis revealed that short periods of food
restriction followed by refeeding predominantly affected fast muscle, with
changes in muscle fiber diameter and miRNAs expression. There was an increase in
the mRNA levels of catabolic pathways components (FBXO25, ATG12, BCL2) and
energetic metabolism-related genes (PGC1alpha and SDHA), together with a decrease
in PPARbeta/delta mRNA levels. Interestingly, an increase in mRNA levels of
anabolic genes (PI3K and mTORC1 complex: mTOR, mLST8 and RAPTOR) was also
observed during food restriction. After refeeding, muscle morphology showed
similar patterns of the control group; the majority of genes were slightly up- or
down-regulated in fast and slow muscle, respectively; the levels of all miRNAs
increased in fast muscle and some of them decreased in slow muscle. Our findings
demonstrated that a short period of food restriction in juvenile pacu had a
considerable impact on fast muscle, increasing the expression of anabolic (PI3K
and mTORC1 complex: mTOR, mLST8 and RAPTOR) and energetic metabolism genes. The
miRNAs (miR-1, miR-206, miR-199 and miR-23a) were more expressed during refeeding
and while their target genes (IGF-1, mTOR, PGC1alpha and MAFbx), presented a
decreased expression. The alterations in mTORC1 complex observed during fasting
may have influenced the rates of protein synthesis by using amino acids from
protein degradation as an alternative mechanism to preserve muscle phenotype and
metabolic demand maintenance.
PMID- 28505180
TI - Empathic nonverbal behavior increases ratings of both warmth and competence in a
medical context.
AB - In medicine, it is critical that clinicians demonstrate both empathy (perceived
as warmth) and competence. Perceptions of these qualities are often intuitive and
are based on nonverbal behavior. Emphasizing both warmth and competence may prove
problematic, however, because there is evidence that they are inversely related
in other settings. We hypothesize that perceptions of physician competence will
instead be positively correlated with perceptions of physician warmth and
empathy, potentially due to changing conceptions of the physician's role. We test
this hypothesis in an analog medical context using a large online sample,
manipulating physician nonverbal behaviors suggested to communicate empathy (e.g.
eye contact) and competence (the physician's white coat). Participants rated
physicians displaying empathic nonverbal behavior as more empathic, warm, and
more competent than physicians displaying unempathic nonverbal behavior,
adjusting for mood. We found no warmth/competence tradeoff and, additionally, no
significant effects of the white coat. Further, compared with male participants,
female participants perceived physicians displaying unempathic nonverbal behavior
as less empathic. Given the significant consequences of clinician empathy, it is
important for clinicians to learn how nonverbal behavior contributes to
perceptions of warmth, and use it as another tool to improve their patients'
emotional and physical health.
PMID- 28505181
TI - Overexpression of pyruvate dehydrogenase kinase 1 in retinoblastoma: A potential
therapeutic opportunity for targeting vitreous seeds and hypoxic regions.
AB - Pyruvate dehydrogenase kinase 1 (PDK1), a key enzyme implicated in metabolic
reprogramming of tumors, is induced in several tumors including glioblastoma,
breast cancer and melanoma. However, the role played by PDK1 is not studied in
retinoblastoma (RB). In this study, we have evaluated the expression of PDK1 in
RB clinical samples, and studied its inhibition as a strategy to decrease cell
growth and migration. We show that PDK1 is specifically overexpressed in RB
patient samples especially in vitreous seeds and hypoxic regions and cell lines
compared to control retina using immunohistochemistry and real-time PCR. Our
results further demonstrate that inhibition of PDK1 using small molecule
inhibitors dichloroacetic acid (DCA) and dichloroacetophenone (DAP) resulted in
reduced cell growth and increased apoptosis. We also confirm that combination
treatment of DCA with chemotherapeutic agent carboplatin further enhanced the
therapeutic efficacy compared to single drug treatment. In addition, we observed
changes in glucose uptake, lactate and reactive oxygen species (ROS) levels as
well as decreased cell migration in response to PDK1 inhibition. Additionally, we
show that DCA treatment led to inhibition of PI3K/Akt pathway and reduction in
PDK1 protein levels. Overall, our data suggest that targeting PDK1 could be a
novel therapeutic strategy for RB.
PMID- 28505182
TI - Using NextRAD sequencing to infer movement of herbivores among host plants.
AB - Herbivores often move among spatially interspersed host plants, tracking high
quality resources through space and time. This dispersal is of particular
interest for vectors of plant pathogens. Existing molecular tools to track such
movement have yielded important insights, but often provide insufficient genetic
resolution to infer spread at finer spatiotemporal scales. Here, we explore the
use of Nextera-tagmented reductively-amplified DNA (NextRAD) sequencing to infer
movement of a highly-mobile winged insect, the potato psyllid (Bactericera
cockerelli), among host plants. The psyllid vectors the pathogen that causes
zebra chip disease in potato (Solanum tuberosum), but understanding and managing
the spread of this pathogen is limited by uncertainty about the insect's host
plant(s) outside of the growing season. We identified 1,978 polymorphic loci
among psyllids separated spatiotemporally on potato or in patches of bittersweet
nightshade (S. dulcumara), a weedy plant proposed to be the source of potato
colonizing psyllids. A subset of the psyllids on potato exhibited genetic
similarity to insects on nightshade, consistent with regular movement between
these two host plants. However, a second subset of potato-collected psyllids was
genetically distinct from those collected on bittersweet nightshade; this
suggests that a currently unrecognized source, i.e., other nightshade patches or
a third host-plant species, could be contributing to psyllid populations in
potato. Oftentimes, dispersal of vectors of pathogens must be tracked at a fine
scale in order to understand, predict, and manage disease spread. We demonstrate
that emerging sequencing technologies that detect genome-wide SNPs of a vector
can be used to infer such localized movement.
PMID- 28505183
TI - High-order epistasis shapes evolutionary trajectories.
AB - High-order epistasis-where the effect of a mutation is determined by interactions
with two or more other mutations-makes small, but detectable, contributions to
genotype-fitness maps. While epistasis between pairs of mutations is known to be
an important determinant of evolutionary trajectories, the evolutionary
consequences of high-order epistasis remain poorly understood. To determine the
effect of high-order epistasis on evolutionary trajectories, we computationally
removed high-order epistasis from experimental genotype-fitness maps containing
all binary combinations of five mutations. We then compared trajectories through
maps both with and without high-order epistasis. We found that high-order
epistasis strongly shapes the accessibility and probability of evolutionary
trajectories. A closer analysis revealed that the magnitude of epistasis, not its
order, predicts is effects on evolutionary trajectories. We further find that
high-order epistasis makes it impossible to predict evolutionary trajectories
from the individual and paired effects of mutations. We therefore conclude that
high-order epistasis profoundly shapes evolutionary trajectories through genotype
fitness maps.
PMID- 28505184
TI - SteadyCom: Predicting microbial abundances while ensuring community stability.
AB - Genome-scale metabolic modeling has become widespread for analyzing microbial
metabolism. Extending this established paradigm to more complex microbial
communities is emerging as a promising way to unravel the interactions and
biochemical repertoire of these omnipresent systems. While several modeling
techniques have been developed for microbial communities, little emphasis has
been placed on the need to impose a time-averaged constant growth rate across all
members for a community to ensure co-existence and stability. In the absence of
this constraint, the faster growing organism will ultimately displace all other
microbes in the community. This is particularly important for predicting steady
state microbiota composition as it imposes significant restrictions on the
allowable community membership, composition and phenotypes. In this study, we
introduce the SteadyCom optimization framework for predicting metabolic flux
distributions consistent with the steady-state requirement. SteadyCom can be
rapidly converged by iteratively solving linear programming (LP) problem and the
number of iterations is independent of the number of organisms. A significant
advantage of SteadyCom is compatibility with flux variability analysis. SteadyCom
is first demonstrated for a community of four E. coli double auxotrophic mutants
and is then applied to a gut microbiota model consisting of nine species, with
representatives from the phyla Bacteroidetes, Firmicutes, Actinobacteria and
Proteobacteria. In contrast to the direct use of FBA, SteadyCom is able to
predict the change in species abundance in response to changes in diets with
minimal additional imposed constraints on the model. By randomizing the uptake
rates of microbes, an abundance profile with a good agreement to experimental gut
microbiota is inferred. SteadyCom provides an important step towards the cross
cutting task of predicting the composition of a microbial community in a given
environment.
PMID- 28505187
TI - Recurrence of Dupuytren's contracture: A consensus-based definition.
AB - PURPOSE: One of the major determinants of Dupyutren disease (DD) treatment
efficacy is recurrence of the contracture. Unfortunately, lack of agreement in
the literature on what constitutes recurrence makes it nearly impossible to
compare the multiple treatments alternatives available today. The aim of this
study is to bring an unbiased pool of experts to agree upon what would be
considered a recurrence of DD after treatment; and from that consensus establish
a much-needed definition for DD recurrence. METHODS: To reach an expert consensus
on the definition of recurrence we used the Delphi method and invited 43
Dupuytren's research and treatment experts from 10 countries to participate by
answering a series of questionnaire rounds. After each round the answers were
analyzed and the experts received a feedback report with another questionnaire
round to further hone in of the definition. We defined consensus when at least
70% of the experts agreed on a topic. RESULTS: Twenty-one experts agreed to
participate in this study. After four consensus rounds, we agreed that DD
recurrence should be defined as "more than 20 degrees of contracture recurrence
in any treated joint at one year post-treatment compared to six weeks post
treatment". In addition, "recurrence should be reported individually for every
treated joint" and afterwards measurements should be repeated and reported
yearly. CONCLUSION: This study provides the most comprehensive to date definition
of what should be considered recurrence of DD. These standardized criteria should
allow us to better evaluate the many treatment alternatives.
PMID- 28505185
TI - Combined treatment of miltefosine and paromomycin delays the onset of
experimental drug resistance in Leishmania infantum.
AB - BACKGROUND: Since miltefosine monotherapy against visceral leishmaniasis (VL)
caused by Leishmania donovani has been discontinued in the Indian subcontinent
due to an increase in the number of treatment failures, single dose liposomal
amphotericin B is now advocated as a treatment option of choice. Paromomycin
miltefosine combination therapy can be used as substitute first-line treatment in
regions without cold-chain potential. Previous laboratory studies in the closely
related species Leishmania infantum have demonstrated that paromomycin
monotherapy fairly rapidly selects for resistance producing a phenotype with
increased fitness. Given the possible clinical implications of these findings for
the current field situation, the present study aimed to identify the potential
hazards of paromomycin-miltefosine combination therapy. PRINCIPAL FINDINGS: Drug
interaction studies using the fixed-ratio isobologram method revealed an
indifferent interaction between paromomycin and miltefosine. In hamsters infected
with L. infantum, the combination resulted in cumulative efficacy in reducing
parasite burdens in the liver, spleen and bone marrow. Selected resistant lines
against the single drugs did not display cross-resistance. When the intracellular
amastigote stage was repeatedly exposed to the paromomycin-miltefosine
combination, either in vitro or in vivo, no significant susceptibility decrease
towards either drug was noted. CONCLUSIONS: These results suggest that
implementation of paromomycin-miltefosine combination therapy indeed could
represent a safe and affordable treatment option for L. donovani VL as
miltefosine appears to overrule the anticipated rapid development of PMM
resistance.
PMID- 28505186
TI - In Situ complement activation and T-cell immunity in leprosy spectrum: An
immunohistological study on leprosy lesional skin.
AB - Mycobacterium leprae (M. leprae) infection causes nerve damage and the condition
worsens often during and long after treatment. Clearance of bacterial antigens
including lipoarabinomannan (LAM) during and after treatment in leprosy patients
is slow. We previously demonstrated that M. leprae LAM damages peripheral nerves
by in situ generation of the membrane attack complex (MAC). Investigating the
role of complement activation in skin lesions of leprosy patients might provide
insight into the dynamics of in situ immune reactivity and the destructive
pathology of M. leprae. In this study, we analyzed in skin lesions of leprosy
patients, whether M. leprae antigen LAM deposition correlates with the deposition
of complement activation products MAC and C3d on nerves and cells in the
surrounding tissue. Skin biopsies of paucibacillary (n = 7), multibacillary
leprosy patients (n = 7), and patients with erythema nodosum leprosum (ENL) (n =
6) or reversal reaction (RR) (n = 4) and controls (n = 5) were analyzed. The
percentage of C3d, MAC and LAM deposition was significantly higher in the skin
biopsies of multibacillary compared to paucibacillary patients (p = <0.05, p =
<0.001 and p = <0.001 respectively), with a significant association between LAM
and C3d or MAC in the skin biopsies of leprosy patients (r = 0.9578, p< 0.0001
and r = 0.8585, p<0.0001 respectively). In skin lesions of multibacillary
patients, MAC deposition was found on axons and co-localizing with LAM. In skin
lesions of paucibacillary patients, we found C3d positive T-cells in and
surrounding granulomas, but hardly any MAC deposition. In addition, MAC
immunoreactivity was increased in both ENL and RR skin lesions compared to non
reactional leprosy patients (p = <0.01 and p = <0.01 respectively). The present
findings demonstrate that complement is deposited in skin lesions of leprosy
patients, suggesting that inflammation driven by complement activation might
contribute to nerve damage in the lesions of these patients. This should be
regarded as an important factor in M. leprae nerve damage pathology.
PMID- 28505188
TI - Early childhood lung function is a stronger predictor of adolescent lung function
in cystic fibrosis than early Pseudomonas aeruginosa infection.
AB - OBJECTIVE: Pseudomonas aeruginosa has been suggested as a major determinant of
poor pulmonary outcomes in cystic fibrosis (CF), although other factors play a
role. Our objective was to investigate the association of early childhood
Pseudomonas infection on differences in lung function in adolescence with CF.
METHODS: Two populations of subjects with CF were studied: from the Gene Modifier
Study (GMS), 346 F508del homozygotes with severe vs. mild adolescent lung
disease, and from the Colorado Newborn Screen Study (NBS) 172 subjects diagnosed
with CF by newborn screening. Associations of Pseudomonas infection and lung
function in early childhood with lung function in adolescence were investigated
using multivariate linear regression analyses. RESULTS: Among GMS subjects, those
with severe adolescent lung disease had worse lung function in childhood (FEV1 25
percentage points lower) compared to subjects with mild adolescent lung disease,
regardless of early childhood Pseudomonas status. Among NBS subjects, those with
lowest adolescent lung function had significantly lower early childhood lung
function and faster rate of decline in FEV1 than subjects with highest adolescent
lung function; early Pseudomonas infection was not associated with rate of FEV1
decline. The strongest predictor of adolescent lung function was early childhood
lung function. Subjects with a higher percentage of cultures positive for
Pseudomonas before age 6 or a lower BMI at 2-4 years old also had lower
adolescent lung function, though these associations were not as strong as with
early childhood lung function. CONCLUSIONS: In separate analyses of two distinct
populations of subjects with CF, we found a strong correlation between lower lung
function in early childhood and adolescence, regardless of early childhood
Pseudomonas status. Factors in addition to early Pseudomonas infection have a
strong impact on lung function in early childhood in CF. Further exploration may
identify novel underlying genetic or environmental factors that predispose
children with CF to early loss of lung function.
PMID- 28505189
TI - Small and big Hodgkin-Reed-Sternberg cells of Hodgkin lymphoma cell lines L-428
and L-1236 lack consistent differences in gene expression profiles and are
capable to reconstitute each other.
AB - The hallmark of classical Hodgkin lymphoma (cHL) is the presence of giant, mostly
multinucleated Hodgkin-Reed-Sternberg (HRS) cells. Whereas it has recently been
shown that giant HRS cells evolve from small Hodgkin cells by incomplete
cytokinesis and re-fusion of tethered sister cells, it remains unsolved why this
phenomenon particularly takes place in this lymphoma and what the differences
between these cell types of variable sizes are. The aim of the present study was
to characterize microdissected small and giant HRS cells by gene expression
profiling and to assess differences of clonal growth behavior as well as
susceptibility toward cytotoxic intervention between these different cell types
to provide more insight into their distinct cellular potential. Applying
stringent filter criteria, only two differentially expressed genes between small
and giant HRS cells, SHFM1 and LDHB, were identified. With looser filter
criteria, 13 genes were identified to be differentially overexpressed in small
compared to giant HRS cells. These were mainly related to energy metabolism and
protein synthesis, further suggesting that small Hodgkin cells resemble the
proliferative compartment of cHL. SHFM1, which is known to be involved in the
generation of giant cells, was downregulated in giant RS cells at the RNA level.
However, reduced mRNA levels of SHFM1, LDHB and HSPA8 did not translate into
decreased protein levels in giant HRS cells. In cell culture experiments it was
observed that the fraction of small and big HRS cells was adjusted to the basic
level several days after enrichment of these populations via cell sorting,
indicating that small and big HRS cells can reconstitute the full spectrum of
cells usually observed in the culture. However, assessment of clonal growth of
HRS cells indicated a significantly reduced potential of big HRS cells to form
single cell colonies. Taken together, our findings pinpoint to strong
similarities but also some differences between small and big HRS cells.
PMID- 28505190
TI - Dynamic interaction between fetal adversity and a genetic score reflecting
dopamine function on developmental outcomes at 36 months.
AB - BACKGROUND: Fetal adversity, evidenced by poor fetal growth for instance, is
associated with increased risk for several diseases later in life. Classical cut
offs to characterize small (SGA) and large for gestational age (LGA) newborns are
used to define long term vulnerability. We aimed at exploring the possible
dynamism of different birth weight cut-offs in defining vulnerability in
developmental outcomes (through the Bayley Scales of Infant and Toddler
Development), using the example of a gene vs. fetal adversity interaction
considering gene choices based on functional relevance to the studied outcome.
METHODS: 36-month-old children from an established prospective birth cohort
(Maternal Adversity, Vulnerability, and Neurodevelopment) were classified
according to birth weight ratio (BWR) (SGA <=0.85, LGA >1.15, exploring a wide
range of other cut-offs) and genotyped for polymorphisms associated with dopamine
signaling (TaqIA-A1 allele, DRD2-141C Ins/Ins, DRD4 7-repeat, DAT1-10- repeat,
Met/Met-COMT), composing a score based on the described function, in which
hypofunctional variants received lower scores. RESULTS: There were 251 children
(123 girls and 128 boys). Using the classic cut-offs (0.85 and 1.15), there were
no statistically significant interactions between the neonatal groups and the
dopamine genetic score. However, when changing the cut-offs, it is possible to
see ranges of BWR that could be associated with vulnerability to poorer
development according to the variation in the dopamine function. CONCLUSION: The
classic birth weight cut-offs to define SGA and LGA newborns should be seen with
caution, as depending on the outcome in question, the protocols for long-term
follow up could be either too inclusive-therefore most costly, or unable to
screen true vulnerabilities-and therefore ineffective to establish early
interventions and primary prevention.
PMID- 28505192
TI - Large herbivores in novel ecosystems - Habitat selection by red deer (Cervus
elaphus) in a former brown-coal mining area.
AB - After centuries of range contraction, many megafauna species are recolonizing
parts of Europe. One example is the red deer (Cervus elaphus), which was able to
expand its range and is now found in half the areas it inhabited in the beginning
of the 19th century. Herbivores are important ecosystem engineers, influencing
e.g. vegetation. Knowledge on their habitat selection and their influence on
ecosystems might be crucial for future landscape management, especially for
hybrid and novel ecosystems emerging in post-industrial landscapes. In this
study, red deer habitat selection was studied in a former brown-coal mining area
in Denmark. Here, natural settings were severely changed during the mining
activity and its current landscape is in large parts managed by hunters as
suitable deer habitat. We assessed red deer habitat preferences through feces
presence and camera traps combined with land cover data from vegetation sampling,
remote sensing and official geographic data. Red deer occurrence was negatively
associated with human disturbance and positively associated with forage
availability, tree cover and mean terrain height. Apparently, red deer are
capable of recolonizing former industrial landscapes quite well if key conditions
such as forage abundance and cover are appropriate. In the absence of carnivores,
human disturbance, such as a hunting regime is a main reason why deer avoid
certain areas. The resulting spatial heterogeneity red deer showed in their
habitat use of the study area might be a tool to preserve mosaic landscapes of
forest and open habitats and thus promote biodiversity in abandoned post
industrial landscapes.
PMID- 28505191
TI - Lp25 membrane protein from pathogenic Leptospira spp. is associated with
rhabdomyolysis and oliguric acute kidney injury in a guinea pig model of
leptospirosis.
AB - Acute kidney injury (AKI) from leptospirosis is frequently nonoliguric with hypo-
or normokalemia. Higher serum potassium levels are observed in non-survivor
patients and may have been caused by more severe AKI, metabolic disarrangement,
or rhabdomyolysis. An association between the creatine phosphokinase (CPK) level
and maximum serum creatinine level has been observed in these patients, which
suggests that rhabdomyolysis contributes to severe AKI and hyperkalemia. LipL32
and Lp25 are conserved proteins in pathogenic strains of Leptospira spp., but
these proteins have no known function. This study evaluated the effect of these
proteins on renal function in guinea pigs. Lp25 is an outer membrane protein that
appears responsible for the development of oliguric AKI associated with
hyperkalemia induced by rhabdomyolysis (e.g., elevated CPK, uric acid and serum
phosphate). This study is the first characterization of a leptospiral outer
membrane protein that is associated with severe manifestations of leptospirosis.
Therapeutic methods to attenuate this protein and inhibit rhabdomyolysis-induced
AKI could protect animals and patients from severe forms of this disease and
decrease mortality.
PMID- 28505193
TI - The Drosophila orthologue of the INT6 onco-protein regulates mitotic microtubule
growth and kinetochore structure.
AB - INT6/eIF3e is a highly conserved component of the translation initiation complex
that interacts with both the 26S proteasome and the COP9 signalosome, two
complexes implicated in ubiquitin-mediated protein degradation. The INT6 gene was
originally identified as the insertion site of the mouse mammary tumor virus
(MMTV), and later shown to be involved in human tumorigenesis. Here we show that
depletion of the Drosophila orthologue of INT6 (Int6) results in short mitotic
spindles and deformed centromeres and kinetochores with low intra-kinetochore
distance. Poleward flux of microtubule subunits during metaphase is reduced,
although fluorescence recovery after photobleaching (FRAP) demonstrates that
microtubules remain dynamic both near the kinetochores and at spindle poles.
Mitotic progression is delayed during metaphase due to the activity of the
spindle assembly checkpoint (SAC). Interestingly, a deubiquitinated form of the
kinesin Klp67A (a putative orthologue of human Kif18A) accumulates near the
kinetochores in Int6-depleted cells. Consistent with this finding, Klp67A
overexpression mimics the Int6 RNAi phenotype. Furthermore, simultaneous
depletion of Int6 and Klp67A results in a phenotype identical to RNAi of just
Klp67A, which indicates that Klp67A deficiency is epistatic over Int6 deficiency.
We propose that Int6-mediated ubiquitination is required to control the activity
of Klp67A. In the absence of this control, excess of Klp67A at the kinetochore
suppresses microtubule plus-end polymerization, which in turn results in reduced
microtubule flux, spindle shortening, and centromere/kinetochore deformation.
PMID- 28505194
TI - Comparative effectiveness of angiotensin-converting enzyme inhibitors versus
angiotensin II receptor blockers for major renal outcomes in patients with
diabetes: A 15-year cohort study.
AB - BACKGROUND: Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II
receptor blockers (ARBs) are considered to have similar renoprotective effects;
so far there has been no consensus about their priorities. This study aimed to
compare ACEIs and ARBs for major renal outcomes and survival in a 15-year cohort
of adults with diabetes. METHODS: This study utilized Taiwan's medical and
pharmacy claims data in the Longitudinal Cohort of Diabetes Patients. The primary
outcome was long-term dialysis, and secondary outcomes were hospitalization for
acute kidney injury, hospitalization for hyperkalemia, all-cause death,
cardiovascular death, and non-cardiovascular death. Cox proportional hazards
models were used to estimate the hazard ratios (HRs) and 95% confidence intervals
(CIs) for outcomes comparing ACEIs with ARBs. We conducted subgroup analyses and
interaction tests among patients with different age and comorbid diseases.
RESULTS: A total of 34,043 patients received ACEIs and 23,772 patients received
ARBs. No differences were found for primary or secondary outcomes in the main
analyses. ACEIs showed significantly lower hazard than ARBs for long-term
dialysis among patients with cardiovascular disease (HR 0.80, 95% CI 0.66-0.97,
interaction P = 0.003) or chronic kidney disease (0.81, 0.71-0.93, interaction P
= 0.001). CONCLUSIONS: Our analyses show similar effects of ACEIs and ARBs in
patients with diabetes. However, ACEIs might provide additional renoprotective
effects among patients who have cardiovascular disease or chronic kidney disease.
PMID- 28505195
TI - Dose escalation study to evaluate safety, tolerability and efficacy of
intravenous etoposide phosphate administration in 27 dogs with multicentric
lymphoma.
AB - Comparative oncology has shown that naturally occurring canine cancers are of
valuable and translatable interest for the understanding of human cancer biology
and the characterization of new therapies. This work was part of a comparative
oncology project assessing a new, clinical-stage topoisomerase II inhibitor and
comparing it with etoposide in dogs with spontaneous lymphoma with the objective
to translate findings from dogs to humans. Etoposide is a topoisomerase II
inhibitor widely used in various humans' solid and hematopoietic cancer, but
little data is available concerning its potential antitumor efficacy in dogs.
Etoposide phosphate is a water-soluble prodrug of etoposide which is expected to
be better tolerated in dogs. The objectives of this study were to assess the
safety, the tolerability and the efficacy of intravenous etoposide phosphate in
dogs with multicentric lymphoma. Seven dose levels were evaluated in a
traditional 3+3 phase I design. Twenty-seven owned-dogs with high-grade
multicentric lymphoma were enrolled and treated with three cycles of etoposide
phosphate IV injections every 2 weeks. Adverse effects were graded according to
the Veterinary Cooperative Oncology Group criteria. A complete end-staging was
realized 45 days after inclusion. The maximal tolerated dose was 300 mg/m2. At
this dose level, the overall response rate was 83.3% (n = 6, 3 PR and 2 CR). Only
a moderate reversible gastrointestinal toxicity, no severe myelotoxicity and no
hypersensitivity reaction were reported at this dose level. Beyond the
characterization of etoposide clinical efficacy in dogs, this study underlined
the clinical and therapeutic homologies between dog and human lymphomas.
PMID- 28505196
TI - Unveiling a novel transient druggable pocket in BACE-1 through molecular
simulations: Conformational analysis and binding mode of multisite inhibitors.
AB - The critical role of BACE-1 in the formation of neurotoxic beta-amyloid peptides
in the brain makes it an attractive target for an efficacious treatment of
Alzheimer's disease. However, the development of clinically useful BACE-1
inhibitors has proven to be extremely challenging. In this study we examine the
binding mode of a novel potent inhibitor (compound 1, with IC50 80 nM) designed
by synergistic combination of two fragments-huprine and rhein-that individually
are endowed with very low activity against BACE-1. Examination of crystal
structures reveals no appropriate binding site large enough to accommodate 1.
Therefore we have examined the conformational flexibility of BACE-1 through
extended molecular dynamics simulations, paying attention to the highly flexible
region shaped by loops 8-14, 154-169 and 307-318. The analysis of the protein
dynamics, together with studies of pocket druggability, has allowed us to detect
the transient formation of a secondary binding site, which contains Arg307 as a
key residue for the interaction with small molecules, at the edge of the
catalytic cleft. The formation of this druggable "floppy" pocket would enable the
binding of multisite inhibitors targeting both catalytic and secondary sites.
Molecular dynamics simulations of BACE-1 bound to huprine-rhein hybrid compounds
support the feasibility of this hypothesis. The results provide a basis to
explain the high inhibitory potency of the two enantiomeric forms of 1, together
with the large dependence on the length of the oligomethylenic linker.
Furthermore, the multisite hypothesis has allowed us to rationalize the
inhibitory potency of a series of tacrine-chromene hybrid compounds, specifically
regarding the apparent lack of sensitivity of the inhibition constant to the
chemical modifications introduced in the chromene unit. Overall, these findings
pave the way for the exploration of novel functionalities in the design of
optimized BACE-1 multisite inhibitors.
PMID- 28505197
TI - Structure of Ca2+-binding protein-6 from Entamoeba histolytica and its
involvement in trophozoite proliferation regulation.
AB - Cell cycle of Entamoeba histolytica, the etiological agent of amoebiasis, follows
a novel pathway, which includes nuclear division without the nuclear membrane
disassembly. We report a nuclear localized Ca2+-binding protein from E.
histolytica (abbreviated hereafter as EhCaBP6), which is associated with
microtubules. We determined the 3D solution NMR structure of EhCaBP6, and
identified one unusual, one canonical and two non-canonical cryptic EF-hand
motifs. The cryptic EF-II and EF-IV pair with the Ca2+-binding EF-I and EF-III,
respectively, to form a two-domain structure similar to Calmodulin and Centrin
proteins. Downregulation of EhCaBP6 affects cell proliferation by causing delays
in transition from G1 to S phase, and inhibition of DNA synthesis and
cytokinesis. We also demonstrate that EhCaBP6 modulates microtubule dynamics by
increasing the rate of tubulin polymerization. Our results, including structural
inferences, suggest that EhCaBP6 is an unusual CaBP involved in regulating cell
proliferation in E. histolytica similar to nuclear Calmodulin.
PMID- 28505198
TI - Strongyloides seroprevalence before and after an ivermectin mass drug
administration in a remote Australian Aboriginal community.
AB - BACKGROUND: Strongyloides seroprevalence is hyper-endemic in many Australian
Aboriginal and Torres Strait Islander communities, ranging from 35-60%. We report
the impact on Strongyloides seroprevalence after two oral ivermectin mass drug
administrations (MDAs) delivered 12 months apart in a remote Australian
Aboriginal community. METHODS: Utilizing a before and after study design, we
measured Strongyloides seroprevalence through population census with sequential
MDAs at baseline and month 12. Surveys at months 6 and 18 determined changes in
serostatus. Serodiagnosis was undertaken by ELISA that used sonicated
Strongyloides ratti antigen to detect anti-Strongyloides IgG. Non-pregnant
participants weighing >=15 kg were administered a single 200 MUg/kg ivermectin
dose, repeated after 10-42 days if Strongyloides and/or scabies was diagnosed;
others followed a standard alternative algorithm. A questionnaire on clinical
symptoms was administered to identify adverse events from treatment and self
reported symptoms associated with serostatus. FINDINGS: We surveyed 1013
participants at the baseline population census and 1060 (n = 700 from baseline
cohort and 360 new entrants) at month 12. Strongyloides seroprevalence fell from
21% (175/818) at baseline to 5% at month 6. For participants from the baseline
cohort this reduction was sustained at month 12 (34/618, 6%), falling to 2% at
month 18 after the second MDA. For new entrants to the cohort at month 12,
seroprevalence reduced from 25% (75/297) to 7% at month 18. Strongyloides
positive seroconversions for the baseline cohort six months after each MDA were
2.5% (4/157) at month 6 and 1% at month 18, whilst failure to serorevert remained
unchanged at 18%. At 12 months, eosinophilia was identified in 59% of baseline
seropositive participants and 89% of seropositive new entrants, compared with
47%baseline seronegative participants and 51% seronegative new entrants.
Seropositivity was not correlated with haemoglobin or any self-reported clinical
symptoms. Clinical symptoms ascertained on the day of treatment and 24-72 hrs
after, did not identify any adverse events. SIGNIFICANCE: Two community
ivermectin MDAs delivered 12 months apart by trained Aboriginal researchers in
collaboration with non-Indigenous researchers resulted in a sustained and
significant reduction in Strongyloides seroprevalence over 18 months. Similar
reductions were seen in the baseline cohort and new entrants.
PMID- 28505199
TI - Stress and salivary cortisol in emergency medical dispatchers: A randomized
shifts control trial.
AB - Stress at work is a public health concern. Phone operators in emergency medical
dispatch centers are particularly at risk. We aimed to demonstrate that the most
stressful time for emergency medical dispatchers is the shift when they receive
emergency incoming calls, with cortisol as a biomarker of stress. For each
emergency medical dispatcher, we measured outcomes over a control day and during
three types of shift: Incoming emergency call, Dispatch and Re-assessment. The
pattern of shifts was randomized. Saliva was sampled every 15 minutes for 2
hours, i.e. 6 consecutive times, starting 15 minutes after the first life-and
death incoming emergency call between 2 and 5 pm during three types of shift. We
measured saliva cortisol every 2 hours over a control day, from 7am to 9pm.
Perceived stress was assessed by a visual analog scale. We recruited 22 phone
operators aged 36.4+/-10.8 years old (14 women and 8 men). Cortisol values were
higher during the Incoming emergency call shift than during the Dispatch (p =
.04) and Re-assessment (p = .04) shifts. The increase in cortisol levels was
greater in men than in women (p = .009). There were no differences between
control values and those of the three shifts. The kinetics of cortisol increased
with greater perceived stress overall (p < .001) and for each type of shift
(Incoming emergency call, p = .02; Dispatch p = .03; Re-assessment: p < .001).
The kinetics of cortisol in response to incoming emergency calls was greater when
the call was an absolute emergency (p = .03), and also tended to further increase
when a subsequent absolute incoming emergency call was received (p = 0.07). In
conclusion, the incoming emergency call shift carries particular risk for
dispatchers, who have greater perceived stress and a greater increase in cortisol
levels.
PMID- 28505200
TI - Using eDNA to detect the distribution and density of invasive crayfish in the
Honghe-Hani rice terrace World Heritage site.
AB - The Honghe-Hani landscape in China is a UNESCO World Natural Heritage site due to
the beauty of its thousands of rice terraces, but these structures are in danger
from the invasive crayfish Procambarus clarkii. Crayfish dig nest holes, which
collapse terrace walls and destroy rice production. Under the current control
strategy, farmers self-report crayfish and are issued pesticide, but this
strategy is not expected to eradicate the crayfish nor to prevent their spread
since farmers are not able to detect small numbers of crayfish. Thus, we tested
whether environmental DNA (eDNA) from paddy-water samples could provide a
sensitive detection method. In an aquarium experiment, Real-time Quantitative
polymerase chain reaction (qPCR) successfully detected crayfish, even at a
simulated density of one crayfish per average-sized paddy (with one false
negative). In a field test, we tested eDNA and bottle traps against direct counts
of crayfish. eDNA successfully detected crayfish in all 25 paddies where crayfish
were observed and in none of the 7 paddies where crayfish were absent. Bottle
trapping was successful in only 68% of the crayfish-present paddies. eDNA
concentrations also correlated positively with crayfish counts. In sum, these
results suggest that single samples of eDNA are able to detect small crayfish
populations, but not perfectly. Thus, we conclude that a program of repeated eDNA
sampling is now feasible and likely reliable for measuring crayfish geographic
range and for detecting new invasion fronts in the Honghe Hani landscape, which
would inform regional control efforts and help to prevent the further spread of
this invasive crayfish.
PMID- 28505201
TI - Assessment of antibody library diversity through next generation sequencing and
technical error compensation.
AB - Antibody libraries are important resources to derive antibodies to be used for a
wide range of applications, from structural and functional studies to
intracellular protein interference studies to developing new diagnostics and
therapeutics. Whatever the goal, the key parameter for an antibody library is its
complexity (also known as diversity), i.e. the number of distinct elements in the
collection, which directly reflects the probability of finding in the library an
antibody against a given antigen, of sufficiently high affinity. Quantitative
evaluation of antibody library complexity and quality has been for a long time
inadequately addressed, due to the high similarity and length of the sequences of
the library. Complexity was usually inferred by the transformation efficiency and
tested either by fingerprinting and/or sequencing of a few hundred random library
elements. Inferring complexity from such a small sampling is, however, very
rudimental and gives limited information about the real diversity, because
complexity does not scale linearly with sample size. Next-generation sequencing
(NGS) has opened new ways to tackle the antibody library complexity quality
assessment. However, much remains to be done to fully exploit the potential of
NGS for the quantitative analysis of antibody repertoires and to overcome current
limitations. To obtain a more reliable antibody library complexity estimate here
we show a new, PCR-free, NGS approach to sequence antibody libraries on Illumina
platform, coupled to a new bioinformatic analysis and software (Diversity
Estimator of Antibody Library, DEAL) that allows to reliably estimate the
complexity, taking in consideration the sequencing error.
PMID- 28505202
TI - Serum HBV surface antigen positivity is associated with low prevalence of
metabolic syndrome: A meta-analysis.
AB - BACKGROUND AND AIM: As there is conflicting evidence for the relationship between
hepatitis B virus surface antigen (HBsAg) positivity and the prevalence of
metabolic syndrome (MetS), we performed a meta-analysis to investigate whether
HBsAg positivity affects the incidence of MetS. METHODS: Observational studies on
the relationship between HBsAg positivity and MetS were obtained from PubMed, Web
of Science, and the Cochrane Library in April 2016. The pooled odds ratios (ORs)
of MetS and its components (central obesity, increased fasting glucose, increased
blood pressure, dyslipidemia) for subjects with or without HBsAg positivity were
synthesized. The standardized mean difference of MetS components between HBsAg
positive participants and healthy controls was calculated. Heterogeneity was
explored with subgroup analysis and sensitivity analysis. Publication bias was
detected using Egger's test and Begg's test. RESULTS: Thirty studies were
eligible for meta-analysis. The MetS OR for HBsAg-positive participants was
significantly decreased compared with the controls [OR = 0.80, 95% confidence
interval (CI), 0.70-0.90]. The negative effect of HBsAg positivity on elevated
triglycerides (OR = 0.62, 95% CI, 0.59-0.64) was strong, while that for increased
fasting blood glucose was weak (OR = 0.94, 95% CI, 0.90-0.98). The pooled ORs of
central obesity (OR = 0.97, 95% CI, 0.91-1.04), reduced high-density lipoprotein
cholesterol (OR = 0.98, 95% CI, 0.83-1.14), and elevated blood pressure (OR =
1.00, 95% CI, 0.80-1.25) for HBsAg-positive participants were all not
significantly different compared with the controls. No publication bias was
detected. CONCLUSIONS: Serum HBsAg positivity is inversely associated with the
prevalence of MetS. Among the five components of MetS, elevated triglycerides had
the strongest inverse relationship with HBsAg positivity.
PMID- 28505203
TI - Cytological and morphological analysis of hybrids between Brassicoraphanus, and
Brassica napus for introgression of clubroot resistant trait into Brassica napus
L.
AB - Interspecific hybridization is a powerful tool for improvement of crop species,
it has the potential to broaden the genetic base and create new plant forms for
breeding programs. Synthetic allopolyploid is a widely-used model for the study
of genetic recombination and fixed heterosis in Brassica. In Brassica napus
breeding, identification and introgression of new sources of clubroot resistance
trait from wild or related species into it by hybridization is a long-term crop
management strategy for clubroot disease. Radish (Raphanus sativus L.) is a close
relative of the Brassica and most radish accessions are immune to the clubroot
disease. A synthesized allotetraploid Brassicoraphanus (RRCC, 2n = 36) between R.
sativus cv. HQ-04 (2n = 18, RR) and Brassica oleracea var. alboglabra (L.H
Bailey) (2n = 18, CC) proved resistant of multiple clubroot disease pathogen P.
brassicae. To predict the possibility to transfer the clubroot resistance trait
from the RR subgenome of allotetraploid Brassicoraphanus (RRCC, 2n = 36) into
Brassica napus (AACC, 2n = 38), we analyzed the frequency of chromosome pairings
in the F1 hybrids produced from a cross between B. napus cv. HS5 and the
allotetraploid, characterize the genomic composition of some backcrossed progeny
(BC1) using GISH, BAC-FISH and AFLP techniques. The level of intergenomic pairing
between A and R genomes in the F1 hybrid was high, allosyndetic bivalents formed
in 73.53% PMCs indicative of significant level of homeologous recombination
between two genomes and high probability of incorporating chromosomal
segments/genes from R-genome into A/C-genomes. The BC1 plants inherited variant
extra R chromosomes or fragments from allotetraploid as revealed by GISH and AFLP
analysis. 13.51% BC2 individuals were resistant to clubroot disease, and several
resistance lines had high pollen fertility, Overall, the genetic material
presented in this work represents a potential new genetic resource for practical
use in breeding B. napus clubroot resistant cultivars.
PMID- 28505205
TI - Associations of mid-pregnancy HbA1c with gestational diabetes and risk of adverse
pregnancy outcomes in high-risk Taiwanese women.
AB - BACKGROUND: The objective of this study was to investigate the associations among
the mid-pregnancy glycated hemoglobin A1c (HbA1c) level, gestational diabetes
(GDM), and risk of adverse pregnancy outcomes in women without overt diabetes and
with positive 50-g, 1-h glucose challenge test (GCT) results (140 mg/dL or
greater). METHODS: This prospective study enrolled 1,989 pregnant Taiwanese
women. A two-step approach, including a 50-g, 1-h GCT and 100-g, 3-h oral glucose
tolerance test (OGTT), was employed for the diagnosis of GDM at weeks 23-32. The
mid-pregnancy HbA1c level was measured at the time the OGTT was performed. A
receiver operating characteristic (ROC) curve was used to determine the
relationship between the mid-pregnancy HbA1c level and GDM. Multiple logistic
regression models were implemented to assess the relationships between the mid
pregnancy HbA1c level and adverse pregnancy outcomes. RESULTS: An ROC curve
demonstrated that the optimal mid-pregnancy HbA1c cut-off point to predict GDM,
as diagnosed by the Carpenter-Coustan criteria using a two-step approach, was
5.7%. The area under the ROC curve of the mid-pregnancy HbA1c level for GDM was
0.70. Compared with the levels of 4.5-4.9%, higher mid-pregnancy HbA1c levels
(5.0-5.4, 5.5-5.9, 6.0-6.4, 6.5-6.9, and >7.0%) were significantly associated
with increased risks of gestational hypertension or preeclampsia, preterm
delivery, admission to the neonatal intensive care unit, low birth weight, and
macrosomia (the odds ratio [OR] ranges were 1.20-9.98, 1.31-5.16, 0.88-3.15, 0.89
4.10, and 2.22-27.86, respectively). CONCLUSIONS: The mid-pregnancy HbA1c level
was associated with various adverse pregnancy outcomes in high-risk Taiwanese
women. However, it lacked adequate sensitivity and specificity to replace the two
step approach in the diagnosis of GDM. The current study comprised a single
center prospective study; thus, additional, randomized control design studies are
required.
PMID- 28505204
TI - Compartment-specific distribution of human intestinal innate lymphoid cells is
altered in HIV patients under effective therapy.
AB - Innate lymphocyte cells (ILCs), a novel family of innate immune cells are
considered to function as key orchestrators of immune defences at mucosal
surfaces and to be crucial for maintaining an intact intestinal barrier.
Accordingly, first data suggest depletion of ILCs to be involved in human
immunodeficiency virus (HIV)-associated damage of the intestinal mucosa and
subsequent microbial translocation. However, although ILCs are preferentially
localized at mucosal surfaces, only little is known regarding distribution and
function of ILCs in the human gastrointestinal tract. Here, we show that in HIV(
) individuals composition and functional capacity of intestinal ILCs is
compartment-specific with group 1 ILCs representing the major fraction in the
upper gastrointestinal (GI) tract, whereas ILC3 are the predominant population in
ileum and colon, respectively. In addition, we present first data indicating that
local cytokine concentrations, especially that of IL-7, might modulate
composition of gut ILCs. Distribution of intestinal ILCs was significantly
altered in HIV patients, who displayed decreased frequency of total ILCs in ileum
and colon owing to reduced numbers of both CD127(+)ILC1 and ILC3. Of note,
frequency of colonic ILC3 was inversely correlated with serum levels of I-FABP
and sCD14, surrogate markers for loss of gut barrier integrity and microbial
translocation, respectively. Both expression of the IL-7 receptor CD127 on ILCs
as well as mucosal IL-7 mRNA levels were decreased in HIV(+) patients, especially
in those parts of the GI tract with reduced ILC frequencies, suggesting that
impaired IL-7 responses of ILCs might contribute to incomplete reconstitution of
ILCs under effective anti-retroviral therapy. This is the first report comparing
distribution and function of ILCs along the intestinal mucosa of the entire human
gastrointestinal tract in HIV(+) and HIV(-) individuals.
PMID- 28505206
TI - Effects of alphaTAT1 and HDAC5 on axonal regeneration in adult neurons.
AB - The role of posttranslational modifications in axonal injury and regeneration has
been widely studied but there has been little consensus over the mechanism by
which each modification affects adult axonal growth. Acetylation is known to play
an important role in a variety of neuronal functions and its homeostasis is
controlled by two enzyme families: the Histone Deacetylases (HDACs) and Histone
Acetyl Transferases (HATs). Recent studies show that HDAC5 deacetylates
microtubules in the axonal cytoplasm as part of an injury-induced regeneration
response, but little is known about how acetylation of microtubules plays a role.
Alpha-tubulin acetyl transferase (alphaTAT1) is a microtubule specific acetyl
transferase that binds to microtubules and directly affects microtubule stability
in cells. We hypothesize that increasing tubulin acetylation may play an
important role in increasing the rate of axonal growth. In this study, we
infected cultured adult DRG neurons with alphaTAT1 and alphaTAT1-D157N, a
catalytically inactive mutant, and HDAC5, using lentiviruses. We found that
alphaTAT1 significantly increases tubulin acetylation in 293T cells and DRG
neurons but alphaTAT1-D157N does not. Furthermore, in neurons infected with
alphaTAT1, a significant increase in acetylated tubulin was detected towards the
distal portion of the axon but this increase was not detected in neurons infected
with alphaTAT1-D157N. However, we found a significant increase in axon lengths of
DRG neurons after alphaTAT1 and alphaTAT1-D157N infection, but no effect on axon
lengths after infection with HDAC5. Our results suggest that while alphaTAT1 may
play a role in axon growth in vitro, the increase is not directly due to
acetylation of axonal microtubules. Our results also show that HDAC5
overexpression in the axonal cytoplasm does not play a crucial role in axonal
regeneration of cultured DRG neurons. We expressed these genes in DRG neurons in
adult rats and performed a sciatic nerve crush. We found that axons did not
regenerate any better when infected with any of the constructs compared with
control animals. Thus, while alphaTAT1 may be important for axonal growth in
vitro, neither alphaTAT1 nor HDAC5 had an effect in vivo on the regeneration of
sciatic nerves.
PMID- 28505208
TI - Neuromuscular function of the quadriceps muscle during isometric maximal,
submaximal and submaximal fatiguing voluntary contractions in knee osteoarthrosis
patients.
AB - INTRODUCTION: Knee osteoarthrosis (KOA) is commonly associated with a dysfunction
of the quadriceps muscle which contributes to alterations in motor performance.
The underlying neuromuscular mechanisms of muscle dysfunction are not fully
understood. The main objective of this study was to analyze how KOA affects
neuromuscular function of the quadriceps muscle during different contraction
intensities. MATERIALS AND METHODS: The following parameters were assessed in 20
patients and 20 healthy controls: (i) joint position sense, i.e. position control
(mean absolute error, MAE) at 30 degrees and 50 degrees of knee flexion, (ii)
simple reaction time task performance, (iii) isometric maximal voluntary torque
(IMVT) and root mean square of the EMG signal (RMS-EMG), (iv) torque control,
i.e. accuracy (MAE), absolute fluctuation (standard deviation, SD), relative
fluctuation (coefficient of variation, CV) and periodicity (mean frequency, MNF)
of the torque signal at 20%, 40% and 60% IMVT, (v) EMG-torque relationship at
20%, 40% and 60% IMVT and (vi) performance fatigability, i.e. time to task
failure (TTF) at 40% IMVT. RESULTS: Compared to the control group, the KOA group
displayed: (i) significantly higher MAE of the angle signal at 30 degrees
(99.3%; P = 0.027) and 50 degrees (147.9%; P < 0.001), (ii) no significant
differences in reaction time, (iii) significantly lower IMVT (-41.6%; P = 0.001)
and tendentially lower RMS-EMG of the rectus femoris (-33.7%; P = 0.054), (iv)
tendentially higher MAE of the torque signal at 20% IMVT (65.9%; P = 0.068),
significantly lower SD of the torque signal at all three torque levels and
greater MNF at 60% IMVT (44.8%; P = 0.018), (v) significantly increased RMS-EMG
of the vastus lateralis at 20% (70.8%; P = 0.003) and 40% IMVT (33.3%; P =
0.034), significantly lower RMS-EMG of the biceps femoris at 20% (-63.6%; P =
0.044) and 40% IMVT (-41.3%; P = 0.028) and tendentially lower at 60% IMVT (
24.3%; P = 0.075) and (vi) significantly shorter TTF (-51.1%; P = 0.049).
CONCLUSION: KOA is not only associated with a deterioration of IMVT and
neuromuscular activation, but also with an impaired position and torque control
at submaximal torque levels, an altered EMG-torque relationship and a higher
performance fatigability of the quadriceps muscle. It is recommended that the
rehabilitation includes strengthening and fatiguing exercises at maximal and
submaximal force levels.
PMID- 28505207
TI - Immuno-related polymorphisms and cervical cancer risk: The IARC multicentric case
control study.
AB - A small proportion of women who are exposed to infection with human
papillomavirus (HPV) develop cervical cancer (CC). Genetic factors may affect the
risk of progression from HPV infection to cervical precancer and cancer. We used
samples from the International Agency for Research on Cancer (IARC) multicentric
case-control study to evaluate the association of selected genetic variants with
CC. Overall, 790 CC cases and 717 controls from Algeria, Morocco, India and
Thailand were included. Cervical exfoliated cells were obtained from control
women and cervical exfoliated cells or biopsy specimens from cases. HPV
positivity was determined using a general primer GP5+/6+ mediated PCR.
Unconditional logistic regression was used to estimate odds ratios (OR) and
corresponding 95% confidence intervals (CI) of host genotypes with CC risk, using
the homozygous wild type genotype as the referent category and adjusting by age
and study centre. The association of polymorphisms with the risk of high-risk HPV
positivity among controls was also evaluated. A statistically significant
association was observed between single nucleotide polymorphism (SNP) CHR6
rs2844511 and CC risk: the OR for carriers of the GA or GG genotypes was 0.70
(95% CI: 0.43-1.14) and 0.61 (95% CI: 0.38-0.98), respectively, relative to
carriers of AA genotype (p-value for trend 0.03). We also observed associations
of borderline significance with the TIPARP rs2665390 polymorphism, which was
previously found to be associated with ovarian and breast cancer, and with the
EXOC1 rs13117307 polymorphism, which has been linked to cervical cancer in a
large study in a Chinese population. We confirmed the association between CC and
the rs2844511 polymorphism previously identified in a GWAS study in a Swedish
population. The major histocompatibility region of chromosome 6, or perhaps other
SNPs in linkage disequilibrium, may be involved in CC onset.
PMID- 28505209
TI - Genetic identification and evolutionary trends of the seagrass Halophila
nipponica in temperate coastal waters of Korea.
AB - Although seagrass species in the genus Halophila are generally distributed in
tropical or subtropical regions, H. nipponica has been reported to occur in
temperate coastal waters of the northwestern Pacific. Because H. nipponica occurs
only in the warm temperate areas influenced by the Kuroshio Current and shows a
tropical seasonal growth pattern, such as severely restricted growth in low water
temperatures, it was hypothesized that this temperate Halophila species diverged
from tropical species in the relatively recent evolutionary past. We used a
phylogenetic analysis of internal transcribed spacer (ITS) regions to examine the
genetic variability and evolutionary trend of H. nipponica. ITS sequences of H.
nipponica from various locations in Korea and Japan were identical or showed very
low sequence divergence (less than 3-base pair, bp, difference), confirming that
H. nipponica from Japan and Korea are the same species. Halophila species in the
section Halophila, which have simple phyllotaxy (a pair of petiolate leaves at
the rhizome node), were separated into five well-supported clades by maximum
parsimony analysis. H. nipponica grouped with H. okinawensis and H. gaudichaudii
from the subtropical regions in the same clade, the latter two species having
quite low ITS sequence divergence from H. nipponica (7-15-bp). H. nipponica in
Clade I diverged 2.95 +/- 1.08 million years ago from species in Clade II, which
includes H. ovalis. According to geographical distribution and genetic
similarity, H. nipponica appears to have diverged from a tropical species like H.
ovalis and adapted to warm temperate environments. The results of divergence time
estimates suggest that the temperate H. nipponica is an older species than the
subtropical H. okinawensis and H. gaudichaudii and they may have different
evolutionary histories.
PMID- 28505210
TI - Whole exome sequencing of a consanguineous family identifies the possible
modifying effect of a globally rare AK5 allelic variant in celiac disease
development among Saudi patients.
AB - Celiac disease (CD), a multi-factorial auto-inflammatory disease of the small
intestine, is known to occur in both sporadic and familial forms. Together HLA
and Non-HLA genes can explain up to 50% of CD's heritability. In order to
discover the missing heritability due to rare variants, we have exome sequenced a
consanguineous Saudi family presenting CD in an autosomal recessive (AR) pattern.
We have identified a rare homozygous insertion c.1683_1684insATT, in the
conserved coding region of AK5 gene that showed classical AR model segregation in
this family. Sequence validation of 200 chromosomes each of sporadic CD cases and
controls, revealed that this extremely rare (EXac MAF 0.000008) mutation is
highly penetrant among general Saudi populations (MAF is 0.62). Genotype and
allelic distribution analysis have indicated that this AK5 (c.1683_1684insATT)
mutation is negatively selected among patient groups and positively selected in
the control group, in whom it may modify the risk against CD development
[p<0.002]. Our observation gains additional support from computational analysis
which predicted that Iso561 insertion shifts the existing H-bonds between 400th
and 556th amino acid residues lying near the functional domain of adenylate
kinase. This shuffling of amino acids and their H-bond interactions is likely to
disturb the secondary structure orientation of the polypeptide and induces the
gain-of-function in nucleoside phosphate kinase activity of AK5, which may
eventually down-regulates the reactivity potential of CD4+ T-cells against gluten
antigens. Our study underlines the need to have population-specific genome
databases to avoid false leads and to identify true candidate causal genes for
the familial form of celiac disease.
PMID- 28505212
TI - Disentangling niche competition from grazing mortality in phytoplankton dilution
experiments.
AB - The dilution method is the principal tool used to infer in situ microzooplankton
grazing rates. However, grazing is the only mortality process considered in the
theoretical model underlying the interpretation of dilution method experiments.
Here we evaluate the robustness of mortality estimates inferred from dilution
experiments when there is concurrent niche competition amongst phytoplankton.
Using a combination of mathematical analysis and numerical simulations, we find
that grazing rates may be overestimated-the degree of overestimation is related
to the importance of niche competition relative to microzooplankton grazing. In
response, we propose a conceptual method to disentangle the effects of niche
competition and grazing by diluting out microzooplankton, but not phytoplankton.
Our theoretical results suggest this revised "Z-dilution" method can robustly
infer grazing mortality, regardless of the dominant phytoplankton mortality
driver in our system. Further, we show it is possible to independently estimate
both grazing mortality and niche competition if the classical and Z-dilution
methods can be used in tandem. We discuss the significance of these results for
quantifying phytoplankton mortality rates; and the feasibility of implementing
the Z-dilution method in practice, whether in model systems or in complex
communities with overlap in the size distributions of phytoplankton and
microzooplankton.
PMID- 28505213
TI - Dupuytren's disease: How to recognize its early signs.
AB - Palmar skin dimpling and nodule or cord formation signal advancing disease.
Treatments vary in effectiveness--in part, depending on condition severity.
PMID- 28505214
TI - Publication and Reporting of the Results of Postmarket Studies for Drugs Required
by the US Food and Drug Administration, 2009 to 2013.
PMID- 28505216
TI - Could Albumin Be a Biomarker to Monitor the Effect of Intravenous Immunoglobulin
on Guillain-Barre Syndrome?
PMID- 28505211
TI - Fronto-temporal interactions are functionally relevant for semantic control in
language processing.
AB - Semantic cognition, i.e. processing of meaning is based on semantic
representations and their controlled retrieval. Semantic control has been shown
to be implemented in a network that consists of left inferior frontal (IFG), and
anterior and posterior middle temporal gyri (a/pMTG). We aimed to disrupt
semantic control processes with continuous theta burst stimulation (cTBS) over
left IFG and pMTG and to study whether behavioral effects are moderated by
induced alterations in resting-state functional connectivity. To this end, we
applied real cTBS over left IFG and left pMTG as well as sham stimulation on 20
healthy participants in a within-subject design. Stimulation was followed by
resting-state functional magnetic resonance imaging and a semantic priming
paradigm. Resting-state functional connectivity of regions of interest in left
IFG, pMTG and aMTG revealed highly interconnected left-lateralized fronto
temporal networks representing the semantic system. We did not find any
significant direct modulation of either task performance or resting-state
functional connectivity by effective cTBS. However, after sham cTBS, functional
connectivity between IFG and pMTG correlated with task performance under high
semantic control demands in the semantic priming paradigm. These findings provide
evidence for the functional relevance of interactions between IFG and pMTG for
semantic control processes. This interaction was functionally less relevant after
cTBS over aIFG which might be interpretable in terms of an indirect disruptive
effect of cTBS.
PMID- 28505215
TI - Patient Dismissal by Primary Care Practices.
PMID- 28505218
TI - Establishing and Achieving National Goals for Preventing Lead Toxicity and
Exposure in Children.
PMID- 28505217
TI - Effect of Combined Patient Decision Aid and Patient Navigation vs Usual Care for
Colorectal Cancer Screening in a Vulnerable Patient Population: A Randomized
Clinical Trial.
AB - Importance: Colorectal cancer (CRC) screening is underused, especially among
vulnerable populations. Decision aids and patient navigation are potentially
complementary interventions for improving CRC screening rates, but their combined
effect on screening completion is unknown. Objective: To determine the combined
effect of a CRC screening decision aid and patient navigation compared with usual
care on CRC screening completion. Design, Setting, and Participants: In this
randomized clinical trial, data were collected from January 2014 to March 2016 at
2 community health center practices, 1 in North Carolina and 1 in New Mexico,
serving vulnerable populations. Patients ages 50 to 75 years who had average CRC
risk, spoke English or Spanish, were not current with recommended CRC screening,
and were attending primary care visits were recruited and randomized 1:1 to
intervention or control arms. Interventions: Intervention participants viewed a
CRC screening decision aid in English or Spanish immediately before their
clinician encounter. The decision aid promoted screening and presented
colonoscopy and fecal occult blood testing as screening options. After the
clinician encounter, intervention patients received support for screening
completion from a bilingual patient navigator. Control participants viewed a food
safety video before the encounter and otherwise received usual care. Main
Outcomes and Measures: The primary outcome was CRC screening completion within 6
months of the index study visit assessed by blinded medical record review.
Results: Characteristics of the 265 participants were as follows: their mean age
was 58 years; 173 (65%) were female, 164 (62%) were Latino; 40 (15%) were white
non-Latino; 61 (23%) were black or of mixed race; 191 (78%) had a household
income of less than $20 000; 101 (38%) had low literacy; 75 (28%) were on
Medicaid; and 91 (34%) were uninsured. Intervention participants were more likely
to complete CRC screening within 6 months (68% vs 27%); adjusted-difference, 40
percentage points (95% CI, 29-51 percentage points). The intervention was more
effective in women than in men (50 vs 21 percentage point increase, interaction P
= .02). No effect modification was observed across other subgroups. Conclusions
and Relevance: A patient decision aid plus patient navigation increased the rate
of CRC screening completion in compared with usual care invulnerable primary care
patients. Trial Registration: clinicaltrials.gov Identifier: NCT02054598.
PMID- 28505219
TI - 64Cu-DOTA-trastuzumab PET imaging for HER2-specific primary lesions of breast
cancer.
PMID- 28505220
TI - Multicenter Evaluation of the Bruker MALDI Biotyper CA System for the
Identification of Clinically Important Bacteria and Yeasts.
AB - Objectives: A report on the multicenter evaluation of the Bruker MALDI Biotyper
CA System (MBT-CA; Bruker Daltonics, Billerica, MA) for the identification of
clinically important bacteria and yeasts. Methods: In total, 4,399 isolates of
medically important bacteria and yeasts were assessed in the MBT-CA. These
included 2,262 aerobic gram-positive (AGP) bacteria, 792 aerobic gram-negative
(AGN) bacteria 530 anaerobic (AnA) bacteria, and 815 yeasts (YSTs). Three
processing methods were assesed. Results: Overall, 98.4% (4,329/4,399) of all
bacterial and yeast isolates were correctly identified to the genus and
species/species complex level, and 95.7% of isolates were identified with a high
degree of confidence. The percentage correctly identified and the percentage
identified correctly with a high level of confidence, respectively, were as
follows: AGP bacteria (98.6%/96.5%), AGN bacteria (98.5%/96.8%), AnA bacteria
(98.5%/97.4%), and YSTs (97.8%/87.6%). The extended direct transfer method was
only minimally superior to the direct transfer method for bacteria (89.9% vs
86.8%, respectively) but significantly superior for yeast isolates (74.0% vs
48.9%, respectively). Conclusions: The Bruker MALDI Biotyper CA System accurately
identifies most clinically important bacteria and yeasts and has optional
processing methods to improve isolate characterization.
PMID- 28505221
TI - Combining PI3K and PARP inhibitors for breast and ovarian cancer treatment.
PMID- 28505222
TI - Discourse Characteristics in Aphasia Beyond the Western Aphasia Battery Cutoff.
AB - Purpose: This study examined discourse characteristics of individuals with
aphasia who scored at or above the 93.8 cutoff on the Aphasia Quotient subtests
of the Western Aphasia Battery-Revised (WAB-R; Kertesz, 2007). They were compared
with participants without aphasia and those with anomic aphasia. Method:
Participants were from the AphasiaBank database and included 28 participants who
were not aphasic by WAB-R score (NABW), 92 participants with anomic aphasia, and
177 controls. Cinderella narratives were analyzed using the Computerized Language
Analysis programs (MacWhinney, 2000). Outcome measures were words per minute,
percent word errors, lexical diversity using the moving average type-token ratio
(Covington, 2007b), main concept production, number of utterances, mean length of
utterance, and proposition density. Results: Results showed that the NABW group
was significantly different from the controls on all measures except MLU and
proposition density. These individuals were compared to participants without
aphasia and those with anomic aphasia. Conclusion: Individuals with aphasia who
score above the WAB-R Aphasia Quotient cutoff demonstrate discourse impairments
that warrant both treatment and special attention in the research literature.
PMID- 28505224
TI - Muscle Bioenergetic Considerations for Intrinsic Laryngeal Skeletal Muscle
Physiology.
AB - Purpose: Intrinsic laryngeal skeletal muscle bioenergetics, the means by which
muscles produce fuel for muscle metabolism, is an understudied aspect of
laryngeal physiology with direct implications for voice habilitation and
rehabilitation. The purpose of this review is to describe bioenergetic pathways
identified in limb skeletal muscle and introduce bioenergetic physiology as a
necessary parameter for theoretical models of laryngeal skeletal muscle function.
Method: A comprehensive review of the human intrinsic laryngeal skeletal muscle
physiology literature was conducted. Findings regarding intrinsic laryngeal
muscle fiber complement and muscle metabolism in human models are summarized and
exercise physiology methodology is applied to identify probable bioenergetic
pathways used for voice function. Results: Intrinsic laryngeal skeletal muscle
fibers described in human models support the fast, high-intensity physiological
requirements of these muscles for biological functions of airway protection.
Inclusion of muscle bioenergetic constructs in theoretical modeling of voice
training, detraining, fatigue, and voice loading have been limited. Conclusions:
Muscle bioenergetics, a key component for muscle training, detraining, and
fatigue models in exercise science, is a little-considered aspect of intrinsic
laryngeal skeletal muscle physiology. Partnered with knowledge of occupation
specific voice requirements, application of bioenergetics may inform novel
considerations for voice habilitation and rehabilitation.
PMID- 28505223
TI - Association of Short Antenatal Corticosteroid Administration-to-Birth Intervals
With Survival and Morbidity Among Very Preterm Infants: Results From the EPICE
Cohort.
AB - Importance: Administration-to-birth intervals of antenatal corticosteroids (ANS)
vary. The significance of this variation is unclear. Specifically, to our
knowledge, the shortest effective administration-to-birth interval is unknown.
Objective: To explore the associations between ANS administration-to-birth
interval and survival and morbidity among very preterm infants. Design, Setting,
and Participants: The Effective Perinatal Intensive Care in Europe (EPICE) study,
a population-based prospective cohort study, gathered data from 19 regions in 11
European countries in 2011 and 2012 on 4594 singleton infants with gestational
ages between 24 and 31 weeks, without severe anomalies and unexposed to repeated
courses of ANS. Data were analyzed November 2016. Exposure: Time from first
injection of ANS to delivery in hours and days. Main Outcomes and Measures: Three
outcomes were studied: in-hospital mortality; a composite of mortality or severe
neonatal morbidity, defined as an intraventricular hemorrhage grade of 3 or
greater, cystic periventricular leukomalacia, surgical necrotizing enterocolitis,
or stage 3 or greater retinopathy of prematurity; and severe neonatal brain
injury, defined as an intraventricular hemorrhage grade of 3 or greater or cystic
periventricular leukomalacia. Results: Of the 4594 infants included in the
cohort, 2496 infants (54.3%) were boys, and the mean (SD) gestational age was
28.5 (2.2) weeks and mean (SD) birth weight was 1213 (400) g. Mortality for the
662 infants (14.4%) unexposed to ANS was 20.6% (136 of 661). Administration of
ANS was associated with an immediate and rapid decline in mortality, reaching a
plateau with more than 50% risk reduction after an administration-to-birth
interval of 18 to 36 hours. A similar pattern for timing was seen for the
composite mortality or morbidity outcome, whereas a significant risk reduction of
severe neonatal brain injury was associated with longer administration-to-birth
intervals (greater than 48 hours). For all outcomes, the risk reduction
associated with ANS was transient, with increasing mortality and risk for severe
neonatal brain injury associated with administration-to-birth intervals exceeding
1 week. Under the assumption of a causal relationship between timing of ANS and
mortality, a simulation of ANS administered 3 hours before delivery to infants
who did not receive ANS showed that their estimated decline in mortality would be
26%. Conclusions and Relevance: Antenatal corticosteroids may be effective even
if given only hours before delivery. Therefore, the infants of pregnant women at
risk of imminent preterm delivery may benefit from its use.
PMID- 28505226
TI - OMTools: a software package for visualizing and processing optical mapping data.
AB - Summary: Optical mapping is a molecular technique capturing specific patterns of
fluorescent labels along DNA molecules. It has been widely applied in assisted
scaffolding in sequence assemblies, microbial strain typing and detection of
structural variations. Various computational methods have been developed to
analyze optical mapping data. However, existing tools for processing and
visualizing optical map data still have many shortcomings. Here, we present
OMTools, an efficient and intuitive data processing and visualization suite to
handle and explore large-scale optical mapping profiles. OMTools includes modules
for visualization (OMView), data processing and simulation. These modules
together form an accessible and convenient pipeline for optical mapping analyses.
Availability and implementation: OMTools is implemented in Java 1.8 and released
under a GPL license. OMTools can be downloaded from
https://github.com/aldenleung/OMTools and run on any standard desktop computer
equipped with a Java virtual machine. Contact: kevinyip@cse.cuhk.edu.hk or
tf.chan@cuhk.edu.hk. Supplementary information: Supplementary data are available
at Bioinformatics online.
PMID- 28505225
TI - Original Findings and Updated Meta-Analysis for the Association Between Maternal
Diabetes and Risk for Congenital Heart Disease Phenotypes.
AB - Maternal diabetes is associated with congenital heart defects (CHDs) as a group,
but few studies have assessed risk for specific CHD phenotypes. We analyzed these
relationships using data from the Texas Birth Defects Registry and statewide
vital records for deliveries taking place in 1999-2009 (n = 48,249 cases). We
used Poisson regression to calculate prevalence ratios for the associations
between maternal diabetes (pregestational or gestational) and each CHD phenotype,
adjusting for potential confounders. Analyses were repeated by type of diabetes.
To address the potential for misclassification bias, we performed logistic
regression, using malformed controls. We also conducted meta-analyses, combining
our estimates of the association between pregestational diabetes and each CHD
phenotype with previous estimates. The prevalence of every CHD phenotype was
greater among women with pregestational diabetes than among nondiabetic women.
Most of these differences were statistically significant (adjusted prevalence
ratios = 2.47-13.20). Associations were slightly attenuated for many CHD
phenotypes among women with gestational diabetes. The observed associations did
not appear to be the result of misclassification bias. In our meta-analysis,
pregestational diabetes was significantly associated with each CHD phenotype.
These findings contribute to a better understanding of the teratogenic effects of
maternal diabetes and improved counseling for risk of specific CHD phenotypes.
PMID- 28505227
TI - Resveratrol Enhances Exercise-Induced Cellular and Functional Adaptations of
Skeletal Muscle in Older Men and Women.
AB - Older men (n = 12) and women (n = 18) 65-80 years of age completed 12 weeks of
exercise and took either a placebo or resveratrol (RSV) (500 mg/d) to test the
hypothesis that RSV treatment combined with exercise would increase mitochondrial
density, muscle fatigue resistance, and cardiovascular function more than
exercise alone. Contrary to our hypothesis, aerobic and resistance exercise
coupled with RSV treatment did not reduce cardiovascular risk further than
exercise alone. However, exercise added to RSV treatment improved the indices of
mitochondrial density, and muscle fatigue resistance more than placebo and
exercise treatments. In addition, subjects that were treated with RSV had an
increase in knee extensor muscle peak torque (8%), average peak torque (14%), and
power (14%) after training, whereas exercise did not increase these parameters in
the placebo-treated older subjects. Furthermore, exercise combined with RSV
significantly improved mean fiber area and total myonuclei by 45.3% and 20%,
respectively, in muscle fibers from the vastus lateralis of older subjects.
Together, these data indicate a novel anabolic role of RSV in exercise-induced
adaptations of older persons and this suggests that RSV combined with exercise
might provide a better approach for reversing sarcopenia than exercise alone.
PMID- 28505230
TI - Degradation and Impurity Profile Study of Ciclopirox Olamine after Pre-column
Derivatization: A Risk Based Approach.
AB - The present study focus on ICH prescribed stress degradation of ciclopirox
olamine after precolumn derivatization. For establishing stability-indicating
assay, the reaction solutions in which different degradation products were formed
were mixed, and the separation was optimized by applying principle of QbD. A risk
analysis tools based on cause-effect risk assessment matrix with control-noise
experimentation (CNX) approach was utilized for identifying the high risk
variable affecting the analytical attributes. Plackett Burman and central
composite design was then used to screen and optimize experimental variables for
DOE studies to resolve ciclopirox olamine and four of its degradation related
impurities with good peak asymmetry and theoretical plates using C18 column. The
method was validated according to ICH and ISO guidelines. To ensure reliability
of the result, evaluation of risk profile, combined standard uncertainty and
expanded uncertainty were also studied. One process related and four unknown
degradation products were identified and characterized by LC-MS/MS study. The
degradation pathways of degradants were proposed based on m/z values.
PMID- 28505228
TI - Associations of Musculoskeletal Pain With Mobility in Older Adults: Potential
Cerebral Mechanisms.
AB - Background: Musculoskeletal pain is highly prevalent and limits mobility in older
adults. A potential mechanism by which pain affects mobility could be through its
negative impact on the brain. We examined whether structural integrity of
cerebral gray and white matter (WM) mediated the relationship between pain and
mobility in community-dwelling older adults. Methods: Musculoskeletal pain, gait
speed, and neuroimaging data were obtained concurrently from the Health ABC study
(mean age = 83/56% female, n = 212). Microstructural gray matter integrity was
measured by mean diffusivity (MD), WM microstructure and macrostructure were
measured by fractional anisotropy (FA) and WM hyperintensities (WMH),
respectively. Regression models were adjusted for gray matter atrophy, age,
gender, medication use, and obesity. Bootstrapped mediation methods were used
(1,000 bootstrapped samples, 95% confidence intervals). Results: The associations
of musculoskeletal pain with WMH (beta = .19, p < .05) and FA (beta = -.18, p <
.05) were robust to adjustment for gender, medication use, age, body mass index
(BMI), and brain atrophy. Participants who experienced both knee and back pain
had a significantly slower gait speed (~0.11 m/s) than those without knee or back
pain (p < .05) independent of gender, medication, age, and BMI. WMH and FA
significantly mediated the pain-gait speed relationship. Associations between
pain and MD were not significant, and MD did not modify the association between
pain and gait speed. Conclusions: Cerebral WM integrity may contribute to the
detrimental effects of musculoskeletal pain on mobility, although pre-existing WM
integrity may also simultaneously amplify pain and decrease mobility. Future
studies are needed to further understand whether successful pain management may
significantly improve both brain health and mobility.
PMID- 28505229
TI - Oligodendrocyte- and Neuron-Specific Nogo-A Restrict Dendritic Branching and
Spine Density in the Adult Mouse Motor Cortex.
AB - Nogo-A has been well described as a myelin-associated inhibitor of neurite
outgrowth and functional neuroregeneration after central nervous system (CNS)
injury. Recently, a new role of Nogo-A has been identified as a negative
regulator of synaptic plasticity in the uninjured adult CNS. Nogo-A is present in
neurons and oligodendrocytes. However, it is yet unclear which of these two pools
regulate synaptic plasticity. To address this question we used newly generated
mouse lines in which Nogo-A is specifically knocked out in (1) oligodendrocytes
(oligoNogo-A KO) or (2) neurons (neuroNogo-A KO). We show that both
oligodendrocyte- and neuron-specific Nogo-A KO mice have enhanced dendritic
branching and spine densities in layer 2/3 cortical pyramidal neurons. These
effects are compartmentalized: neuronal Nogo-A affects proximal dendrites whereas
oligodendrocytic Nogo-A affects distal regions. Finally, we used two-photon laser
scanning microscopy to measure the spine turnover rate of adult mouse motor
cortex layer 5 cells and find that both Nogo-A KO mouse lines show enhanced spine
remodeling after 4 days. Our results suggest relevant control functions of glial
as well as neuronal Nogo-A for synaptic plasticity and open new possibilities for
more selective and targeted plasticity enhancing strategies.
PMID- 28505231
TI - Autologous Stem Cell Transplantation for Refractory Crohn's Disease: Is it Time
to Take a Long-Term View?
PMID- 28505232
TI - Findings of an Observational Study of Neuraminidase Inhibitors Highly Sensitive
to Decision to Exclude 1652 Treated Patients.
PMID- 28505233
TI - Addition of droperidol to prophylactic ondansetron and dexamethasone in children
at high risk for postoperative vomiting. A randomized, controlled, double-blind
study.
AB - Background: : The combination of dexamethasone (DEX), ondansetron (OND) and
droperidol (DRO) is efficacious in preventing postoperative nausea and vomiting
in adults, but has not been well assessed in children. Methods: : Children
undergoing elective surgery under general anaesthesia and considered at high risk
for postoperative vomiting (POV) were randomly assigned to receive a combination
of DEX, OND and placebo (Group A) or a combination of DEX, OND and DRO (Group B).
The primary outcome was the incidence of POV during the first 24 hours after
surgery. We hypothesized that the addition of DRO to the standard antiemetic
prophylaxis would provide a further 15% reduction in the residual risk for POV.
The secondary outcome considered was any adverse event occurring during the
study. Results: : One hundred and fifty-three children, aged three to 16 years,
were randomized to Group A and 162 to Group B. The overall incidence of POV did
not differ significantly between the two groups, with 16 patients in Group A
(10.5%) and 18 in Group B (11.1%) presenting with one or more episodes of POV, P
=0.86. Fewer patients presented with adverse events in Group A (2%) compared with
Group B (8%), P =0.01. Drowsiness and headache were the principal adverse events
reported. Conclusions: : The addition of DRO to a combination of OND and DEX did
not decrease POV frequency below that obtained with the two-drug combination in
children at high risk of POV, but increased the risk of drowsiness. The
combination of DEX and OND should be recommended in children with a high risk of
POV. Clinical trial registration.: NCT01739985.
PMID- 28505235
TI - View-Independent Working Memory Representations of Artificial Shapes in
Prefrontal and Posterior Regions of the Human Brain.
AB - Traditional views of visual working memory postulate that memorized contents are
stored in dorsolateral prefrontal cortex using an adaptive and flexible code. In
contrast, recent studies proposed that contents are maintained by posterior brain
areas using codes akin to perceptual representations. An important question is
whether this reflects a difference in the level of abstraction between posterior
and prefrontal representations. Here, we investigated whether neural
representations of visual working memory contents are view-independent, as
indicated by rotation-invariance. Using functional magnetic resonance imaging and
multivariate pattern analyses, we show that when subjects memorize complex
shapes, both posterior and frontal brain regions maintain the memorized contents
using a rotation-invariant code. Importantly, we found the representations in
frontal cortex to be localized to the frontal eye fields rather than dorsolateral
prefrontal cortices. Thus, our results give evidence for the view-independent
storage of complex shapes in distributed representations across posterior and
frontal brain regions.
PMID- 28505234
TI - Increased Risk for Meningococcal Disease Among Men Who Have Sex With Men in the
United States, 2012-2015.
AB - Background: Several clusters of serogroup C meningococcal disease among men who
have sex with men (MSM) have been reported in the United States in recent years.
The epidemiology and risk of meningococcal disease among MSM is not well
described. Methods: All meningococcal disease cases among men aged 18-64 years
reported to the National Notifiable Disease Surveillance System between January
2012 and June 2015 were reviewed. Characteristics of meningococcal disease cases
among MSM and men not known to be MSM (non-MSM) were described. Annualized
incidence rates among MSM and non-MSM were compared through calculation of the
relative risk and 95% confidence intervals. Isolates from meningococcal disease
cases among MSM were characterized using standard microbiological methods and
whole-genome sequencing. Results: Seventy-four cases of meningococcal disease
were reported among MSM and 453 among non-MSM. Annualized incidence of
meningococcal disease among MSM was 0.56 cases per 100000 population, compared to
0.14 among non-MSM, for a relative risk of 4.0 (95% confidence interval [CI], 3.1
5.1). Among the 64 MSM with known status, 38 (59%) were infected with human
immunodeficiency virus (HIV). HIV-infected MSM had 10.1 times (95% CI, 6.1-16.6)
the risk of HIV-uninfected MSM. All isolates from cluster-associated cases were
serogroup C sequence type 11. Conclusions: MSM are at increased risk for
meningococcal disease, although the incidence of disease remains low. HIV
infection may be an important factor for this increased risk. Routine vaccination
of HIV-infected persons with a quadrivalent meningococcal conjugate vaccine in
accordance with Advisory Committee on Immunization Practices recommendations
should be encouraged.
PMID- 28505237
TI - Erratum.
PMID- 28505236
TI - Could Albumin be a Biomarker to Monitor the Effect of Intravenous Immunoglobulin
on Guillain-Barre Syndrome?-Reply.
PMID- 28505238
TI - Analysis of Species, Subgroups, and Endosymbionts of Bemisia tabaci (Hemiptera:
Aleyrodidae) From Southwestern Cotton Fields in Turkey.
AB - Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) is one of the most important
insect pests worldwide including Turkey. Although there are substantial data
regarding species composition of Turkish B. tabaci populations, the situation is
still not clear and further investigations are needed. Therefore, in this study,
species and subgroups of B. tabaci collected from cotton fields in southwestern
part of Turkey (Antalya, Aydin, Denizli, and Mugla) were determined using
microsatellite analysis, AluI-based mtCOI polymerase chain reaction-random length
polymorphism, and sequencing. Secondary endosymbionts were also determined using
diagnostic species-specific PCR. Middle East Asia Minor 1 (MEAM1), Mediterranean
(MED) Q1, and MED Q2 were the species and subgroups found in this study. The MED
species (85.3%) were found to be more dominant than MEAM1. Species status of B.
tabaci varied depending on the location. Although all samples collected from
Aydin were found to be Q1, three species and subgroups were found in Mugla.
Secondary endosymbionts varied according to species and subgroups. Arsenophonus
was found only from Q2, while Hamiltonella was detected in MEAM1 and Q1. In
addition, high Rickettsia and low Wolbachia infections were detected in MEAM1 and
Q1 populations, respectively. In conclusion, for the first time, we report the
presence and symbiotic communities of Q1 from Turkey. We also found that the
symbiont complement of the Q1 is more congruent with Q1 from Greece than other
regions of the world, which may have some interesting implications for movement
of this invasive subgroup.
PMID- 28505239
TI - FoxO1 Promotes Mitophagy in the Podocytes of Diabetic Male Mice via the
PINK1/Parkin Pathway.
AB - We recently showed that forkhead-box class O1 (FoxO1) activation protects against
high glucose-induced injury by preventing mitochondrial dysfunction in the rat
kidney cortex. In addition, FoxO1 has been reported to mediate putative kinase 1
(PINK1) transcription and promote autophagy in response to mitochondrial
oxidative stress in murine cardiomyocytes. In this study, we ascertained whether
overexpressing FoxO1 in the kidney cortex reverses preestablished diabetic
nephropathy in animal models. The effect of FoxO1 on mitophagy signaling pathways
was evaluated in mouse podocytes. In vivo experiments were performed in male KM
mice. A mouse model of streptozotocin (STZ)-induced type 1 diabetes (T1D) was
used, and lentiviral vectors were injected into the kidney cortex to overexpress
FoxO1. A mouse podocyte cell line was treated with high concentrations of glucose
and genetically modified using lentiviral vectors. We found aberrant
mitochondrial morphology and reduced adenosine triphosphate production. These
mitochondrial abnormalities were due to decreased mitophagy via reduced
phosphatase/tensin homolog on chromosome 10-induced PINK1/Parkin-dependent
signaling. FoxO1 upregulation and PINK1/Parkin pathway activation can
individually restore injured podocytes in STZ-induced T1D mice. Our results link
the antioxidative activity of FoxO1 with PINK1/Parkin-induced mitophagy,
indicating a novel role of FoxO1 in diabetic nephropathy.
PMID- 28505240
TI - Incidence of Gonorrhea and Chlamydia Following Human Immunodeficiency Virus
Preexposure Prophylaxis Among Men Who Have Sex With Men: A Modeling Study.
AB - Background: Preexposure prophylaxis (PrEP) is highly effective for preventing
human immunodeficiency virus (HIV) infection, but risk compensation (RC) in men
who have sex with men (MSM) raises concerns about increased sexually transmitted
infections (STIs). The Center for Disease Control and Prevention's (CDC's) PrEP
guidelines recommend biannual STI screening, which may reduce incidence by
treating STIs that would otherwise remain undiagnosed. We investigated these two
counteracting phenomena. Methods: With a network-based mathematical model of HIV,
Neisseria gonorrhoeae (NG), and Chlamydia trachomatis (CT) transmission dynamics
among MSM in the United States, we simulated PrEP uptake following the
prescription indications and HIV/STI screening recommendations in the CDC
guidelines. Scenarios varied PrEP coverage (the proportion of MSM indicated for
PrEP who received it), RC (a reduction in the per-act probability of condom use),
and the STI screening interval. Results: In our reference scenario (40% coverage,
40% RC), 42% of NG and 40% of CT infections would be averted over the next
decade. A doubling of RC would still result in net STI prevention relative to no
PrEP. STIs declined because PrEP-related STI screening resulted in a 17% and 16%
absolute increase in the treatment of asymptomatic and rectal STIs, respectively.
Screening and timely treatment at quarterly vs biannual intervals would reduce
STI incidence an additional 50%. Conclusions: Implementation of the CDC PrEP
guidelines while scaling up PrEP coverage could result in a significant decline
in STI incidence among MSM. Our study highlights the design of PrEP not only as
antiretroviral medication but as combination HIV/STI prevention incorporating STI
screening.
PMID- 28505242
TI - RE: "RESPONSE AND FOLLOW-UP BIAS IN COHORT STUDIES".
PMID- 28505241
TI - Tri-Ponderal Mass Index vs Body Mass Index in Estimating Body Fat During
Adolescence.
AB - Importance: Body mass index (BMI) is used to diagnose obesity in adolescents
worldwide, despite evidence that weight does not scale with height squared in
adolescents. To account for this, health care providers diagnose obesity using
BMI percentiles for each age (BMI z scores), but this does not ensure that BMI is
accurate in adolescents. Objective: To compare the accuracy of BMI vs other body
fat indices of the form body mass divided by heightn in estimating body fat
levels in adolescents. Design, Setting, and Participants: Cross-sectional data
from the 1999 to 2006 US National Health and Nutrition Examination Survey were
analyzed between September 2015 and December 2016. Main Outcomes and Measures:
Dual-energy x-ray absorptiometry and anthropometric data were used to determine
changes in body fat levels, body proportions, and the scaling relationships among
body mass, height, and percent body fat. To assess the merits of each adiposity
index, 3 criteria were used: stability with age, accuracy in estimating percent
body fat, and accuracy in classifying adolescents as overweight vs normal weight.
Results: Participants included 2285 non-Hispanic white participants aged 8 to 29
years. Percent body fat varied with both age and height during adolescence,
invalidating the standard weight-to-height regression as the way of finding the
optimal body fat index. Because the correct regression model (percent body fat is
proportional to mass divided by heightn) suggested that percent body fat scales
to height with an exponent closer to 3, we therefore focused on the tri-ponderal
mass index (TMI; mass divided by height cubed) as an alternative to BMI z scores.
For ages 8 to 17 years, TMI yielded greater stability with age and estimated
percent body fat better than BMI (R2 = 0.64 vs 0.38 in boys and R2 = 0.72 vs 0.66
in girls). Moreover, TMI misclassified adolescents as overweight vs normal weight
less often than BMI z scores (TMI, 8.4%; 95% CI, 7.3%-9.5% vs BMI, 19.4%; 95% CI,
17.8%-20.0%; P < .001) and performed equally as well as updated BMI percentiles
derived from the same data set (TMI, 8.4%; 95% CI, 7.3%-9.5% vs BMI, 8.0%; 95%
CI, 6.9%-9.1%; P = .62). Conclusions and Relevance: The tri-ponderal mass index
estimates body fat levels more accurately than BMI in non-Hispanic white
adolescents aged 8 to 17 years. Moreover, TMI diagnoses adolescents as overweight
more accurately than BMI z scores and equally as well as updated BMI percentiles
but is much simpler to use than either because it does not involve complicated
percentiles. Taken together, it is worth considering replacing BMI z scores with
TMI to estimate body fat levels in adolescents.
PMID- 28505245
TI - Atrial fibrillation: a left atrial neuro-myopathy?
PMID- 28505243
TI - Association of Dual-Task Gait With Incident Dementia in Mild Cognitive
Impairment: Results From the Gait and Brain Study.
AB - Importance: Gait performance is affected by neurodegeneration in aging and has
the potential to be used as a clinical marker for progression from mild cognitive
impairment (MCI) to dementia. A dual-task gait test evaluating the cognitive
motor interface may predict dementia progression in older adults with MCI.
Objective: To determine whether a dual-task gait test is associated with incident
dementia in MCI. Design, Setting, and Participants: The Gait and Brain Study is
an ongoing prospective cohort study of community-dwelling older adults that
enrolled 112 older adults with MCI. Participants were followed up for 6 years,
with biannual visits including neurologic, cognitive, and gait assessments. Data
were collected from July 2007 to March 2016. Main Outcomes and Measures: Incident
all-cause dementia was the main outcome measure, and single- and dual-task gait
velocity and dual-task gait costs were the independent variables. A
neuropsychological test battery was used to assess cognition. Gait velocity was
recorded under single-task and 3 separate dual-task conditions using an
electronic walkway. Dual-task gait cost was defined as the percentage change
between single- and dual-task gait velocities: ([single-task gait velocity - dual
task gait velocity]/ single-task gait velocity) * 100. Cox proportional hazard
models were used to estimate the association between risk of progression to
dementia and the independent variables, adjusted for age, sex, education,
comorbidities, and cognition. Results: Among 112 study participants with MCI,
mean (SD) age was 76.6 (6.9) years, 55 were women (49.1%), and 27 progressed to
dementia (24.1%), with an incidence rate of 121 per 1000 person-years. Slow
single-task gait velocity (<0.8 m/second) was not associated with progression to
dementia (hazard ratio [HR], 3.41; 95% CI, 0.99-11.71; P = .05)while high dual
task gait cost while counting backward (HR, 3.79; 95% CI, 1.57-9.15; P = .003)
and naming animals (HR, 2.41; 95% CI, 1.04-5.59; P = .04) were associated with
dementia progression (incidence rate, 155 per 1000 person-years). The models
remained robust after adjusting by baseline cognition except for dual-task gait
cost when dichotomized. Conclusions and Relevance: Dual-task gait is associated
with progression to dementia in patients with MCI. Dual-task gait testing is easy
to administer and may be used by clinicians to decide further biomarker testing,
preventive strategies, and follow-up planning in patients with MCI. Trial
Registration: clinicaltrials.gov: NCT03020381.
PMID- 28505244
TI - The Influence of Maternally Derived Antibody and Infant Age at Vaccination on
Infant Vaccine Responses : An Individual Participant Meta-analysis.
AB - Importance: The design of infant immunization schedules requires an understanding
of the factors that determine the immune response to each vaccine antigen. Data
Sources: Deidentified individual participant data from GlaxoSmithKline clinical
trials were obtained through Clinical Study Data Request. The data were requested
on January 2, 2015, and final data were received on April 11, 2016. Study
Selection: Immunogenicity trials of licensed or unlicensed vaccines administered
to infants were included if antibody concentrations in infants were measured
prior to the first dose of vaccine. Data Extraction and Synthesis: The database
was examined; studies that appeared to have appropriate data were reviewed. Main
Outcomes and Measures: Antigen-specific antibody concentration measured 1 month
after priming vaccine doses, before booster vaccination, and 1 month after
booster vaccine doses. Results: A total of 7630 infants from 32 studies in 17
countries were included. Mean (SD) age at baseline was 9.0 (2.3) weeks; 3906
(51.2%) were boys. Preexisting maternal antibody inhibited infant antibody
responses to priming doses for 20 of 21 antigens. The largest effects were
observed for inactivated polio vaccine, where 2-fold higher maternal antibody
concentrations resulted in 20% to 28% lower postvaccination antibody
concentration (geometric mean ratios [GMRs], type 1: 0.80; 95% CI, 0.78-0.83;
type 2: 0.72; 95% CI, 0.69-0.74; type 3: 0.78; 95% CI, 0.75-0.82). For acellular
pertussis antigens, 2-fold higher maternal antibody was associated with 11% lower
postvaccination antibody for pertussis toxoid (GMR, 0.89; 95% CI, 0.87-0.90) and
filamentous hemagglutinin (GMR, 0.89; 95% CI, 0.88-0.90) and 22% lower pertactin
antibody (GMR, 0.78; 95% CI, 0.77-0.80). For tetanus and diphtheria, these
estimates were 13% (GMR, 0.87; 95% CI, 0.86-0.88) and 24% (GMR, 0.76; 95% CI,
0.74-0.77), respectively. The influence of maternal antibody was still evident in
reduced responses to booster doses of acellular pertussis, inactivated polio, and
diphtheria vaccines at 12 to 24 months of age. Children who were older when first
immunized had higher antibody responses to priming doses for 18 of 21 antigens,
after adjusting for the effect of maternal antibody concentrations. The largest
effect was seen for polyribosylribitol phosphate antibody, where responses were
71% higher per month (GMR, 1.71; 95% CI, 1.52-1.92). Conclusions and Relevance:
Maternal antibody concentrations and infant age at first vaccination both
influence infant vaccine responses. These effects are seen for almost all
vaccines contained in global immunization programs and influence immune response
for some vaccines even at the age of 24 months. These data highlight the
potential for maternal immunization strategies to influence established infant
programs.
PMID- 28505246
TI - Effects of long-term exogenous testosterone administration on ovarian morphology,
determined by transvaginal (3D) ultrasound in female-to-male transsexuals.
AB - STUDY QUESTION: Does long-term exogenous testosterone administration result in
polycystic ovarian morphology (PCOM), determined by (3D) transvaginal ultrasound
(TVU) in female-to-male transsexuals (FtMs). SUMMARY ANSWER: Long-term exogenous
testosterone administration in FtMs does not result in PCOM determined by (3D)
TVU. WHAT IS KNOWN ALREADY: The role of androgens in the pathophysiology of
polycystic ovary syndrome (PCOS) is still unclear. From animal studies, intra
ovarian androgens have been suggested to disturb folliculogenesis, through a pro
atretic effect on growing follicles. It remains debatable whether exogenous
androgens induce PCOM in humans. In the past histomorphologic studies indicated
that androgen administration in FtMs could cause PCO-like changes. However,
ultrasound morphology is an established criterion for PCOS, TVU data of ovaries
after prolonged androgen exposure are lacking. STUDY DESIGN, SIZE, DURATION:
Prospective, observational, case-control study, in an academic setting, performed
in 2014-2015, including 56 FtMs and 80 controls. PARTICIPANTS/MATERIALS, SETTING,
METHODS: The study population consisted of adult FtMs treated with long-term
testosterone, as part of their cross-sex hormone treatment, and scheduled for sex
reassignment surgery (bilateral salpingo-oophorectomy). Prior to the operation,
under anaesthetics TVU measurements (3D transvaginal probe 3-9 MHz; HD11, Philips
Ultrasound, Inc.) of the ovaries were performed. The control group consisted of
females from a general population who underwent the same TVU and analysis. Antral
follicle count (AFC) (3D) and ovarian volume (3D) were calculated using
specialized software. PCOM was defined as AFC of 12 or more follicles (2-10 mm)
in at least one ovary. MAIN RESULTS AND THE ROLE OF CHANCE: Prevalence rates of
PCOM were not significantly different in the FtMs compared to controls,
determined by (3D) TVU: 32.1% (17/53) versus 30.7% (23/75), P = 0.87.
LIMITATIONS, REASONS FOR CAUTION: Testosterone levels in FtMs are
supraphysiological, and may not be comparable to the testosterone levels in women
with PCOS. However, we applied a unique and ethically acceptable opportunity of
exploring the effects of androgens on human ovaries. WIDER IMPLICATIONS OF THE
FINDINGS: This first explorative study shows that long-term exogenous
testosterone administration in adult women does not seem to induce PCOM
determined by TVU. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION
NUMBER: The trial was registered at the Dutch Trial Register
(www.trialregister.nl), registration number NTR4784.
PMID- 28505247
TI - Single-cell regulome data analysis by SCRAT.
AB - Summary: Emerging single-cell technologies (e.g. single-cell ATAC-seq, DNase-seq
or ChIP-seq) have made it possible to assay regulome of individual cells. Single
cell regulome data are highly sparse and discrete. Analyzing such data is
challenging. User-friendly software tools are still lacking. We present SCRAT, a
Single-Cell Regulome Analysis Toolbox with a graphical user interface, for
studying cell heterogeneity using single-cell regulome data. SCRAT can be used to
conveniently summarize regulatory activities according to different features
(e.g. gene sets, transcription factor binding motif sites, etc.). Using these
features, users can identify cell subpopulations in a heterogeneous biological
sample, infer cell identities of each subpopulation, and discover distinguishing
features such as gene sets and transcription factors that show different
activities among subpopulations. Availability and implementation: SCRAT is freely
available at https://zhiji.shinyapps.io/scrat as an online web service and at
https://github.com/zji90/SCRAT as an R package. Contact: hji@jhu.edu.
Supplementary information: Supplementary data are available at Bioinformatics
online.
PMID- 28505248
TI - Lactobacilli-lactoferrin interplay in Chlamydia trachomatis infection.
AB - In the cervicovaginal microenvironment, lactobacilli are known to protect against
genital infections and, amongst the host defence compounds, lactoferrin has
recently acquired importance for its anti-microbial and anti-inflammatory
properties. An abnormal genital microenvironment facilitates the acquisition of
pathogens like Chlamydia trachomatis, the leading cause of bacterial sexually
transmitted infections worldwide. The aim of our study is to investigate the
effects of Lactobacillus crispatus, Lactobacillus brevis and bovine lactoferrin
on chlamydial infection, in order to shed light on the complex interplay between
host defence mechanisms and C. trachomatis. We have also evaluated the effect of
these defence factors to modulate the chlamydia-mediated inflammatory state. To
this purpose, we have determined the infectivity and progeny production of C.
trachomatis as well as interleukin-8 and interleukin-6 synthesis. The main result
of our study is that the combination of L. brevis and bovine lactoferrin is the
most effective in inhibiting the early phases (adhesion and invasion) of C.
trachomatis infection of cervical epithelial cells and in decreasing the levels
of both cytokines. In conclusion, the interaction between L. brevis and
lactoferrin seems to play a role in the protection against C. trachomatis,
reducing the infection and regulating the immunomodulatory activity, thus
decreasing the risk of severe complications.
PMID- 28505250
TI - Treating the Symptom but Not the Underlying Disease in Infective Endocarditis: A
Teachable Moment.
PMID- 28505251
TI - False discovery rate control incorporating phylogenetic tree increases detection
power in microbiome-wide multiple testing.
AB - Motivation: Next generation sequencing technologies have enabled the study of the
human microbiome through direct sequencing of microbial DNA, resulting in an
enormous amount of microbiome sequencing data. One unique characteristic of
microbiome data is the phylogenetic tree that relates all the bacterial species.
Closely related bacterial species have a tendency to exhibit a similar
relationship with the environment or disease. Thus, incorporating the
phylogenetic tree information can potentially improve the detection power for
microbiome-wide association studies, where hundreds or thousands of tests are
conducted simultaneously to identify bacterial species associated with a
phenotype of interest. Despite much progress in multiple testing procedures such
as false discovery rate (FDR) control, methods that take into account the
phylogenetic tree are largely limited. Results: We propose a new FDR control
procedure that incorporates the prior structure information and apply it to
microbiome data. The proposed procedure is based on a hierarchical model, where a
structure-based prior distribution is designed to utilize the phylogenetic tree.
By borrowing information from neighboring bacterial species, we are able to
improve the statistical power of detecting associated bacterial species while
controlling the FDR at desired levels. When the phylogenetic tree is mis
specified or non-informative, our procedure achieves a similar power as
traditional procedures that do not take into account the tree structure. We
demonstrate the performance of our method through extensive simulations and real
microbiome datasets. We identified far more alcohol-drinking associated bacterial
species than traditional methods. Availability and implementation: R package
StructFDR is available from CRAN. Contact: chen.jun2@mayo.edu. Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 28505252
TI - Financing and Distribution of Pharmaceuticals in the United States.
PMID- 28505249
TI - Sialic acid deficiency is associated with oxidative stress leading to muscle
atrophy and weakness in GNE myopathy.
AB - Sialic acids are monosaccharides found in terminal sugar chains of cell surfaces
and proteins; they have various biological functions and have been implicated in
health and disease. Genetic defects of the GNE gene which encodes a critical
bifunctional enzyme for sialic acid biosynthesis, lead to GNE myopathy, a disease
manifesting with progressive muscle atrophy and weakness. The likely mechanism of
disease is a lack of sialic acids. There remains, however, an unexplained link
between hyposialylation and the muscle atrophy and weakness. In this study, we
found that muscle proteins were highly modified by S-nitrosylation, and that
oxidative stress-responsive genes were significantly upregulated, in
hyposialylated muscles from human GNE myopathy patients and model mice. In both
in vitro and in vivo models, the production of reactive oxygen species (ROS) was
elevated with cellular hyposialylation, and increasing overall sialylation by
extrinsic sialic acid intake reduced ROS and protein S-nitrosylation. More
importantly, the antioxidant, oral N-acetylcysteine led to amelioration of the
muscle atrophy and weakness in Gne mutant mice. Our data provide evidence of
additional important function of sialic acids as a ROS scavenger in skeletal
muscles, expanding our understanding on how sialic acid deficiency contributes to
disease pathology, and identify oxidative stress as a therapeutic target in GNE
myopathy.
PMID- 28505253
TI - Pulmonary venoplasty with a pericardial conduit in living-donor lobar lung
retransplantation.
AB - In living-donor lobar lung transplantation, donor lobectomies must be performed
carefully for both donors and recipients. Furthermore, the recipients undergo
pneumonectomies rather than lobectomies. Occasionally, anastomosis of the
pulmonary vessels is difficult in living-donor lobar lung transplantation because
of the limited length of the pulmonary vessels in the graft. This report
describes a successful case of pulmonary venoplasty using an autologous
pericardial conduit, which was interposed between the superior pulmonary vein of
the recipient and the inferior pulmonary vein of the donor in living-donor lobar
lung retransplantation. This technique may be required for the success of living
donor lobar lung retransplantation.
PMID- 28505254
TI - Building a Broader Consensus for Health Reform.
PMID- 28505255
TI - Editorial: The many facets of Escherichia coli: from beneficial bug and genetic
workhorse to dangerous menace for plant and creature.
PMID- 28505256
TI - CRISPR/Cas system for yeast genome engineering: advances and applications.
AB - The methods based on the clustered regularly interspaced short palindromic
repeats (CRISPR)/CRISPR-associated (Cas) system have quickly gained popularity
for genome editing and transcriptional regulation in many organisms, including
yeast. This review aims to provide a comprehensive overview of CRISPR application
for different yeast species: from basic principles and genetic design to
applications.
PMID- 28505258
TI - Modelling and mathematical analysis of the M$_{2}$ receptor-dependent joint
signalling and secondary messenger network in CHO cells.
AB - The muscarinic M$_{2}$ receptor is a prominent member of the GPCR family and
strongly involved in heart diseases. Recently published experimental work
explored the cellular response to iperoxo-induced M$_{2}$ receptor stimulation in
Chinese hamster ovary (CHO) cells. To better understand these responses, we
modelled and analysed the muscarinic M$_{2}$ receptor-dependent signalling
pathway combined with relevant secondary messenger molecules using mass action.
In our literature-based joint signalling and secondary messenger model, all
binding and phosphorylation events are explicitly taken into account in order to
enable subsequent stoichiometric matrix analysis. We propose constraint flux
sampling (CFS) as a method to characterize the expected shift of the steady state
reaction flux distribution due to the known amount of cAMP production and PDE4
activation. CFS correctly predicts an experimentally observable influence on the
cytoskeleton structure (marked by actin and tubulin) and in consequence a change
of the optical density of cells. In a second step, we use CFS to simulate the
effect of knock-out experiments within our biological system, and thus to rank
the influence of individual molecules on the observed change of the optical cell
density. In particular, we confirm the relevance of the protein RGS14, which is
supported by current literature. A combination of CFS with Elementary Flux Mode
analysis enabled us to determine the possible underlying mechanism. Our analysis
suggests that mathematical tools developed for metabolic network analysis can
also be applied to mixed secondary messenger and signalling models. This could be
very helpful to perform model checking with little effort and to generate
hypotheses for further research if parameters are not known.
PMID- 28505259
TI - Immune oncology and neuroendocrine tumors.
PMID- 28505257
TI - MicroRNAs in dysfunctional adipose tissue: cardiovascular implications.
AB - In this review, we focus on the emerging role of microRNAs, non-coding RNAs that
regulate gene expression and signaling pathways, in dysfunctional adipose tissue.
We highlight current paradigms of microRNAs involved in adipose differentiation
and function in depots such as white, brown, and beige adipose tissues and
potential implications of microRNA dysregulation in human disease such as
obesity, inflammation, microvasculature dysfunction, and related cardiovascular
diseases. We highlight accumulating studies indicating that adipocyte-derived
microRNAs may not only serve as biomarkers of cardiometabolic disease, but also
may directly regulate gene expression of other tissues. Finally, we discuss the
future prospects, challenges, and emerging strategies for microRNA delivery and
targeting for therapeutic applications in cardiovascular disease states
associated with adipocyte dysfunction.
PMID- 28505260
TI - Evolution of Two Short Interspersed Elements in Callorhinchus milii
(Chondrichthyes, Holocephali) and Related Elements in Sharks and the Coelacanth.
AB - Short interspersed elements (SINEs) are non-autonomous retrotransposons. Although
they usually show fast evolutionary rates, in some instances highly conserved
domains (HCDs) have been observed in elements with otherwise divergent sequences
and from distantly related species. Here, we document the life history of two HCD
SINE families in the elephant shark Callorhinchus milii, one specific to the
holocephalan lineage (CmiSINEs) and another one (SacSINE1-CM) with homologous
elements in sharks and the coelacanth (SacSINE1s, LmeSINE1s). The analyses of
their relationships indicated that these elements share the same 3'-tail, which
would have allowed both elements to rise to high copy number by exploiting the C.
milii L2-2_CM long interspersed element (LINE) enzymes. Molecular clock analysis
on SINE activity in C. milii genome evidenced two replication bursts occurring
right after two major events in the holocephalan evolution: the end-Permian mass
extinction and the radiation of modern Holocephali. Accordingly, the same
analysis on the coelacanth homologous elements, LmeSINE1, identified a
replication wave close to the split age of the two extant Latimeria species. The
genomic distribution of the studied SINEs pointed out contrasting results: some
elements were preferentially sorted out from gene regions, but accumulated in
flanking regions, while others appear more conserved within genes. Moreover, data
from the C. milii transcriptome suggest that these SINEs could be involved in
miRNA biogenesis and may be targets for miRNA-based regulation.
PMID- 28505262
TI - The Basal Ganglia Striosomes Affect the Modulation of Conflicts by Subliminal
Information-Evidence from X-Linked Dystonia Parkinsonism.
AB - Cognitive control is relevant when distracting information induces behavioral
conflicts. Such conflicts can be produced consciously and by subliminally
processed information. Interestingly, both sources of conflict interact
suggesting that they share neural mechanisms. Here, we ask whether conjoint
effects between different sources of conflict are modulated by microstructural
basal ganglia dysfunction. To this end, we carried out an electroencephalography
study and examined event-related potentials (ERPs) including source localization
using a combined flanker-subliminal priming task in patients with X-linked
dystonia Parkinsonism (XDP) and a group of healthy controls. XDP in its early
stages is known to predominantly affect the basal ganglia striosomes. The results
suggest that conjoint effects between subliminal and conscious sources of
conflicts are modulated by the striosomes and were stronger in XDP patients. The
neurophysiological data indicate that this effect is related to modulations in
conflict monitoring and response selection (N2 ERP) mechanisms engaging the
anterior cingulate cortex. Bottom-up perceptual gating, attentional selection,
and motor response activation processes in response to the stimuli (P1, N1, and
lateralized readiness potential ERPs) were unaffected. Taken together, these data
indicate that striosomes modulate the processing of conscious and subliminal
sources of conflict suggesting that microstructural basal ganglia properties are
relevant for cognitive control.
PMID- 28505261
TI - Survival and Causes of Death Among People With Clinically Diagnosed
Synucleinopathies With Parkinsonism: A Population-Based Study.
AB - Importance: To our knowledge, a comprehensive study of the survival and causes of
death of persons with synucleinopathies compared with the general population has
not been conducted. Understanding the long-term outcomes of these conditions may
inform patients and caregivers of the expected disease duration and may help with
care planning. Objective: To compare survival rates and causes of death among
patients with incident, clinically diagnosed synucleinopathies and age- and sex
matched referent participants. Design, Setting, and Participants: This population
based study used the Rochester Epidemiology Project medical records-linkage
system to identify all residents in Olmsted County, Minnesota, who received a
diagnostic code of parkinsonism from 1991 through 2010. A movement-disorders
specialist reviewed the medical records of each individual to confirm the
presence of parkinsonism and determine the type of synucleinopathy. For each
confirmed patient, an age- and sex-matched Olmsted County resident without
parkinsonism was also identified. Main Outcomes and Measures: We determined the
age- and sex-adjusted risk of death for each type of synucleinopathy, the median
time from diagnosis to death, and the causes of death. Results: Of the 461
patients with synucleinopathies, 279 (60.5%) were men, and of the 452 referent
participants, 272 (60.2%) were men. From 1991 through 2010, 461 individuals
received a diagnosis of a synucleinopathy (309 [67%] of Parkinson disease, 81
[17.6%] of dementia with Lewy bodies, 55 [11.9%] of Parkinson disease dementia,
and 16 [3.5%] of multiple system atrophy with parkinsonism). During follow-up,
68.6% (n = 316) of the patients with synucleinopathies and 48.7% (n = 220) of the
referent participants died. Patients with any synucleinopathy died a median of 2
years earlier than referent participants. Patients with multiple system atrophy
with parkinsonism (hazard ratio, 10.51; 95% CI, 2.92-37.82) had the highest risk
of death compared with referent participants, followed by those with dementia
with Lewy bodies (hazard ratio, 3.94; 95% CI, 2.61-5.94), Parkinson disease with
dementia (hazard ratio, 3.86; 95% CI, 2.36-6.30), and Parkinson disease (hazard
ratio, 1.75; 95% CI, 1.39-2.21). Neurodegenerative disease was the most frequent
cause of death listed on the death certificate for patients, and cardiovascular
disease was the most frequent cause of death among referent participants.
Conclusions and Relevance: Individuals with multiple system atrophy with
parkinsonism, dementia with Lewy bodies, and Parkinson disease dementia have
increased mortality compared with the general population. The mortality among
persons with Parkinson disease is only moderately increased compared with the
general population.
PMID- 28505263
TI - Substantial Impairment of Voriconazole Clearance by High-Dose Meropenem in a
Patient With Renal Failure.
AB - A critically ill patient with multiple postoperative infections repeatedly
required profound voriconazole dose reductions whenever high-dose meropenem was
added. Subsequent in vitro assessment confirmed inhibition of cytochrome P450
(CYP) 2C19 and CYP3A4 by meropenem, suggesting that during meropenem treatment,
narrow therapeutic index drugs metabolized by these CYPs require close
monitoring.
PMID- 28505264
TI - Geographical Information Systems in Determination of Cutaneous Leishmaniasis
Spatial Risk Level Based on Distribution of Vector Species in Imamoglu Province,
Adana.
AB - The Imamoglu district located in the southeast of Adana province in Turkey is an
endemic focus of cutaneous leishmaniasis (CL) owing to dominancy of Phlebotomus
tobbi, which is a probable vector of Leishmania infantum. About 11.26% of CL
cases reported each year are from Imamoglu, Adana, and between 2008 and 2015, 223
cases of CL were reported. Leishmania infantum, which may be transmitted by P.
tobbi, Phlebotomus neglectus/syriacus, and Phlebotomus perfiliewi, is referred as
leishmaniasis factor in Adana. Thus, the aim of this study was to map the risk
areas for each sand fly species using remote sensing images based on
environmental factors and geographical characteristics. Two field works in two
consecutive years (2013 and 2014) were conducted and six sand fly species were
caught, four of which were identified as probable vector species. Field work
results were compared with environmental data obtained from satellite images by
univariate and binary logistic regression in PASW. ARCMAP 10.2 software was used
for geographical adjustments, creating a database and estimating a risk model by
using previous risk value formulas. The results showed that the distribution of
three probable leishmaniasis vectors (P. tobbi, P. neglectus/syriacus, and P.
perfiliewi) was associated with normalized difference vegetation index (NDVI),
digital elevation model (DEM), night-time land surface temperature (LSTNIGHT),
and emissivity (EMIS31) values, which were related to the local authorities, who
take these findings into account when deciding on high risk areas for CL.
PMID- 28505267
TI - Integrating Models of Neurologic and Psychiatric Disease.
PMID- 28505266
TI - Guidance for Modifying the Definition of Diseases: A Checklist.
AB - Importance: No guidelines exist currently for guideline panels and others
considering changes to disease definitions. Panels frequently widen disease
definitions, increasing the proportion of the population labeled as unwell and
potentially causing harm to patients. We set out to develop a checklist of
issues, with guidance, for panels to consider prior to modifying a disease
definition. Observations: We assembled a multidisciplinary, multicontinent
working group of 13 members, including members from the Guidelines International
Network, Grading of Recommendations Assessment, Development and Evaluation
working group, and the World Health Organisation. We used a 5-step process to
develop the checklist: (1) a literature review of issues, (2) a draft outline
document, (3) a Delphi process of feedback on the list of issues, (4) a 1-day
face-to-face meeting, and (5) further refinement of the checklist. The literature
review identified 12 potential issues. From these, the group developed an 8-item
checklist that consisted of definition changes, number of people affected,
trigger, prognostic ability, disease definition precision and accuracy, potential
benefits, potential harms, and the balance between potential harms and benefits.
The checklist is accompanied by an explanation of each item and the types of
evidence to assess each one. We used a panel's recent consideration of a proposed
change in the definition of gestational diabetes mellitus (GDM) to illustrate use
of the checklist. Conclusions and Relevance: We propose that the checklist be
piloted and validated by groups developing new guidelines. We anticipate that the
use of the checklist will be a first step to guidance and better documentation of
definition changes prior to introducing modified disease definitions.
PMID- 28505265
TI - The Influence of the Topography of the Ailao Mountains on Congregated Landings of
Airborne Sogatella furcifera (Hemiptera: Delphacidae) Populations.
AB - The Sogatella furcifera (Horvath) is an important migrating rice pest whose
outbreak may be caused by large-scale congregated landings. Hitherto, the
meteorological factors that influence congregated landings were thought to be
rainfall and downdraft. However, for migratory insects on a plateau, low
temperature may be another key factor leading to congregated landings. However,
no reports have been published. Therefore, this paper evaluates the reason for a
large-scale congregated landing in the mountainous area in Yuanjiang via light
trap monitoring. The meteorological backgrounds during light catch peaks were
analyzed using the numeric simulation method. The results were as follows: 1)
from May 7th to May 9th, 2012, the congregated landing of S. furcifera was caused
by precipitation; 2) the congregated landing of S. furcifera on May 10th, 2012,
was a result of low temperatures in the mountainous region. The driving airflow
of S. furcifera climbed along the mountain terrain, which led to a decrease in
temperature with the rise of the mountain terrain. Low temperature created
physiological changes in S. furcifera, forcing S. furcifera to a lower flight
altitude and eventually to a congregated landing; and 3) in the statistical
analysis on 39 peak periods from 2010 to 2016 in the early spring, 20 peaks were
caused by precipitation, and 19 peaks were caused by a low temperature barrier.
Therefore, this study provided evidence of a plateau-migrating S. furcifera
population congregated landing caused by low temperature.
PMID- 28505268
TI - Pharmacodynamics of dose-escalated 'front-loading' polymyxin B regimens against
polymyxin-resistant mcr-1-harbouring Escherichia coli.
AB - Objectives: Gram-negative bacteria harbouring the mcr-1 plasmid are resistant to
the 'last-line' polymyxins and have been reported worldwide. Our objective was to
define the impact of increasing the initial polymyxin B dose intensity against an
mcr-1 -harbouring strain to delineate the impact of plasmid-mediated polymyxin
resistance on the dynamics of bacterial killing and resistance. Methods: A hollow
fibre infection model (HFIM) was used to simulate polymyxin B regimens against an
mcr-1 -harbouring Escherichia coli (MIC 8 mg/L) over 10 days. Four escalating
polymyxin B 'front-loading' regimens (3.33, 6.66, 13.3 or 26.6 mg/kg for one dose
followed by 1.43 mg/kg every 12 h starting 12 h later) simulating human
pharmacokinetics were utilized in the HFIM. A mechanism-based, mathematical model
was developed using S-ADAPT to characterize bacterial killing. Results: The 3.33
mg/kg 'front-loading' regimen resulted in regrowth mirroring the growth control.
The 6.66, 13.3 and 26.6 mg/kg 'front-loading' regimens resulted in maximal
bacterial reductions of 1.91, 3.79 and 6.14 log 10 cfu/mL, respectively.
Irrespective of the early polymyxin B exposure (24 h AUC), population analysis
profiles showed similar growth of polymyxin B-resistant subpopulations. The HFIM
data were well described by the mechanism-based model integrating three
subpopulations (susceptible, intermediate and resistant). Compared with the
susceptible subpopulation of mcr-1 -harbouring E. coli , the resistant
subpopulation had an approximately 10-fold lower rate of killing due to polymyxin
B treatment. Conclusions: Manipulating initial dose intensity of polymyxin B was
not able to overcome plasmid-mediated resistance due to mcr-1 in E. coli . This
reinforces the need to develop new combinatorial strategies to combat these
highly resistant Gram-negative bacteria.
PMID- 28505269
TI - New mutations in non-syndromic primary ovarian insufficiency patients identified
via whole-exome sequencing.
AB - STUDY QUESTION: Is it possible to identify new mutations potentially associated
with non-syndromic primary ovarian insufficiency (POI) via whole-exome sequencing
(WES)? SUMMARY ANSWER: WES is an efficient tool to study genetic causes of POI as
we have identified new mutations, some of which lead to protein destablization
potentially contributing to the disease etiology. WHAT IS KNOWN ALREADY: POI is a
frequently occurring complex pathology leading to infertility. Mutations in only
few candidate genes, mainly identified by Sanger sequencing, have been
definitively related to the pathogenesis of the disease. STUDY DESIGN, SIZE,
DURATION: This is a retrospective cohort study performed on 69 women affected by
POI. PARTICIPANTS/MATERIALS, SETTING, METHODS: WES and an innovative
bioinformatics analysis were used on non-synonymous sequence variants in a subset
of 420 selected POI candidate genes. Mutations in BMPR1B and GREM1 were modeled
by using fragment molecular orbital analysis. MAIN RESULTS AND THE ROLE OF
CHANCE: Fifty-five coding variants in 49 genes potentially related to POI were
identified in 33 out of 69 patients (48%). These genes participate in key
biological processes in the ovary, such as meiosis, follicular development,
granulosa cell differentiation/proliferation and ovulation. The presence of at
least two mutations in distinct genes in 42% of the patients argued in favor of a
polygenic nature of POI. LIMITATIONS, REASONS FOR CAUTION: It is possible that
regulatory regions, not analyzed in the present study, carry further variants
related to POI. WIDER IMPLICATIONS OF THE FINDINGS: WES and the in silico
analyses presented here represent an efficient approach for mapping variants
associated with POI etiology. Sequence variants presented here represents
potential future genetic biomarkers. STUDY FUNDING/COMPETING INTEREST(S): This
study was supported by the Universidad del Rosario and Colciencias (Grants
CS/CIGGUR-ABN062-2016 and 672-2014). Colciencias supported Liliana Catherine
Patino's work (Fellowship: 617, 2013). The authors declare no conflict of
interest.
PMID- 28505270
TI - HTSvis: a web app for exploratory data analysis and visualization of arrayed high
throughput screens.
AB - Summary: Arrayed high-throughput screens (HTS) cover a broad range of
applications using RNAi or small molecules as perturbations and specialized
software packages for statistical analysis have become available. However,
exploratory data analysis and integration of screening results has remained
challenging due to the size of the data sets and the lack of user-friendly tools
for interpretation and visualization of screening results. Here we present
HTSvis, a web application to interactively visualize raw data, perform quality
control and assess screening results from single to multi-channel measurements
such as image-based screens. Per well aggregated raw and analyzed data of various
assay types and scales can be loaded in a generic tabular format. Availability
and implementation: HTSvis is distributed as an open-source R package,
downloadable from https://github.com/boutroslab/HTSvis and can also be accessed
at http://htsvis.dkfz.de . Contact: m.boutros@dkfz.de. Supplementary information:
Supplementary data are available at Bioinformatics online .
PMID- 28505271
TI - Development and psychometric evaluation of a Persian version of the Death
Depression Scale-Revised: a cross-cultural adaptation for patients with advanced
cancer.
AB - Objective: The surfacing of thoughts and depressive affect associated with the
prospect of death are prevalent among patients with advanced cancer. Because
death cognitions and associated negative affect occur along an adaptive-less
adaptive continuum, it is essential that valid and reliable instruments are
available to measure death depression. The present study aimed to determine the
psychometric properties of the Death Depression Scale among Iranian patients with
advanced cancer. Methods: About 497 cancer patients completed a Persian version
of the 21-item Death Depression Scale-Revised. The face, content and construct
validity of the scale were ascertained. Reliability was also assessed using
internal consistency, construct reliability and intra-class correlation
coefficient (ICC). Results: Construct validity determined one factor with an
eigenvalue greater than 1. The model had a good fit (chi2 (179, N = 248) =
520.345, P < 0.001; chi2/df = 2.907, CFI = 0.916, TLI = 0.902, IFI = 0.917, SRMR
= 0.049 and RMSEA = 0.088 (90% confidence interval = 0.079-0.097)) with all
factors loadings greater than 0.5 and statistically significant. The internal
consistency, construct reliability and ICC were greater than 0.70. Convergent
validity of the scale was demonstrated. Conclusions: Findings revealed that the
Persian version of the Death Depression Scale-Revised is valid and reliable, and
may be used to assess and evaluate death depression in Iranian patients with
advanced cancer.
PMID- 28505272
TI - T-tubule remodelling disturbs localized beta2-adrenergic signalling in rat
ventricular myocytes during the progression of heart failure.
AB - Aims: Cardiomyocyte beta2-adrenergic receptor (beta2AR) cyclic adenosine
monophosphate (cAMP) signalling is regulated by the receptors' subcellular
location within transverse tubules (T-tubules), via interaction with structural
and regulatory proteins, which form a signalosome. In chronic heart failure (HF),
beta2ARs redistribute from T-tubules to the cell surface, which disrupts
functional signalosomes and leads to diffuse cAMP signalling. However, the
functional consequences of structural changes upon beta2AR-cAMP signalling during
progression from hypertrophy to advanced HF are unknown. Methods and results: Rat
left ventricular myocytes were isolated at 4-, 8-, and 16-week post-myocardial
infarction (MI), beta2ARs were stimulated either via whole-cell perfusion or
locally through the nanopipette of the scanning ion conductance microscope. cAMP
release was measured via a Forster Resonance Energy Transfer-based sensor Epac2
camps. Confocal imaging of di-8-ANNEPS-stained cells and immunoblotting were used
to determine structural alterations. At 4-week post-MI, T-tubule regularity,
density and junctophilin-2 (JPH2) expression were significantly decreased. The
amplitude of local beta2AR-mediated cAMP in T-tubules was reduced and cAMP
diffused throughout the cytosol instead of being locally confined. This was
accompanied by partial caveolin-3 (Cav-3) dissociation from the membrane. At 8
week post-MI, the beta2AR-mediated cAMP response was observed at the T-tubules
and the sarcolemma (crest). Finally, at 16-week post-MI, the whole cell beta2AR
mediated cAMP signal was depressed due to adenylate cyclase dysfunction, while
overall Cav-3 levels were significantly increased and a substantial portion of
Cav-3 dissociated into the cytosol. Overexpression of JPH2 in failing cells in
vitro or AAV9.SERCA2a gene therapy in vivo did not improve beta2AR-mediated
signal compartmentation or reduce cAMP diffusion. Conclusion: Although changes in
T-tubule structure and beta2AR-mediated cAMP signalling are significant even at 4
week post-MI, progression to the HF phenotype is not linear. At 8-week post-MI
the loss of beta2AR-mediated cAMP is temporarily reversed. Complete
disorganization of beta2AR-mediated cAMP signalling due to changes in functional
receptor localization and cellular structure occurs at 16-week post-MI.
PMID- 28505273
TI - Factor Analysis of an Expanded Halstead-Reitan Battery and the Structure of
Neurocognition.
AB - Objective: The structure of neurocognition is explored by examining the
neurocognitive domains underlying comprehensive neuropsychological assessment of
cognitively healthy individuals. Method: Exploratory factor analysis was
conducted on the adult normative dataset of an expanded Halstead-Reitan Battery
(eHRB), comprising Caucasian and African American participants. The factor
structure contributions of the original HRB, eHRB expansion, and Wechsler
intelligence scales were compared. Demographic effects were examined on composite
factor scores calculated using confirmatory factor analysis. Results: The full
eHRB had an eight-factor structure, with latent constructs including: 'working
memory', 'fluency', 'verbal episodic memory', 'visuospatial cognition'
(visuospatial memory and problem solving), 'perceptual-motor speed' (speed for
processing visual/tactile material and hand-motor execution), 'perceptual
attention' (attention to sensory-perceptual information), 'semantic knowledge'
(knowledge acquired through education and culturally-based experiences), and
'phonological decoding' (grapheme-phoneme processing essential for sounding-out
words). 'Perceptual-motor speed' and 'perceptual attention' were most negatively
associated with age, whereas 'semantic knowledge' and 'phonological decoding'
were most resistant to aging. 'Semantic knowledge' showed the greatest dependence
on demographic background, including education and ethnicity. Gender differences
in cognitive performances were negligible across all domains except 'phonological
decoding' with women slightly outperforming men. The original HRB contributed
four neurocognitive domains, the eHRB expansion three domains, and the Wechsler
scales one additional domain but with restructuring of verbal factors.
Conclusion: Eight neurocognitive domains underlie performance of healthy
cognitive individuals during comprehensive neuropsychological assessment. These
domains serve as framework for understanding the constructs measured by commonly
used neuropsychological tests and may represent the structure of neurocognition.
PMID- 28505274
TI - Migration Analysis of Sogatella furcifera (Hemiptera: Delphacidae) in the
Northeastern Hunan Province in June.
AB - The Sogatella furcifera (Horvath) is a notorious and destructive insect pest,
targeting >4 million hectares of rice cultivated in the Hunan Province. To
understand the immigration dynamics, we collected S. furcifera light trap catches
from 2006 to 2012 at Niangxiang, Linxiang, and Hanshou. We conducted a migration
analysis to estimate the immigration source for the northeastern Hunan Province
in June. Moreover, we dissected the ovaries of S. furcifera to classify
population characteristics. We found that the first appearance of S. furcifera
occurred from late April to early May, with June as the primary time for
migrations into the northeastern Hunan Province. The majority of June ovaries
caught in light traps were Grade I and Grade II, whereas those collected in paddy
fields were Grade III and Grade IV, suggesting that the majority of S. furcifera
immigrated into the northeastern Hunan Province. Our analysis points toward the
northern and central Indo China Peninsula, the southern Hunan Province, the
Guangxi Zhuang Autonomous Region Province, the Guangdong Province, and the Hainan
Province as possible immigration sources of S. furcifera in June for the
northeastern Hunan Province. We propose terrain, loss of forward flow, and wind
shear as causes for the difference observed in light trap catches between
Ningxiang, Linxiang, and Hanshou monitoring stations in the June of 2009. Thus,
our results suggest that monitoring and forecasting of S. furcifera should be
done with particular emphasis in June.
PMID- 28505275
TI - Maternal Stressors and Social Support and Risks of Delivering Babies With
Gastroschisis or Hypospadias.
AB - We examined the association of maternal stressful life events and social support
with risks of gastroschisis and hypospadias, using data from the National Birth
Defects Prevention Study, a population-based case-control study of US births
taking place in 2006-2011. We examined maternal self-reports of 7 life events and
3 sources of social support during the periconceptional period among mothers of
593 gastroschisis cases, 1,142 male hypospadias cases, and 4,399 nonmalformed
controls. Responses to the questions on stressful life events were summed to form
an index (higher is worse), as were responses to questions on social support
(higher is better). We used logistic regression to estimate adjusted odds ratios
and 95% confidence intervals. The adjusted odds ratios for gastroschisis for a 4
point increase in the stress index were 3.5 (95% confidence interval (CI): 2.6,
4.8) among nonteenage mothers (age >=20 years) and 1.0 (95% CI: 0.5, 1.7) among
teenage mothers (age <20 years). The odds ratio for hypospadias (among all
mothers) was 0.8 (95% CI: 0.7, 1.1). Adjusted odds ratios for a social support
score of 3 (versus 0) in the 3 respective groups were 0.6 (95% CI: 0.4, 1.0), 1.0
(95% CI: 0.5, 2.3), and 0.6 (95% CI: 0.4, 0.9). Given the lack of prior research
on these outcomes and stress, results should be interpreted with caution.
PMID- 28505276
TI - African Tick Bite Fever Treated Successfully With Rifampin in a Patient With
Doxycycline Intolerance.
AB - African tick bite fever is the most commonly encountered travel-associated
rickettsiosis, occurring in as many as 5% of travelers returning from rural
subequatorial Africa. This case report illustrates that rifampin represents an
effective alternative to doxycycline for treatment of African tick bite fever in
some selective situations.
PMID- 28505277
TI - Esterification of Ibuprofen in Soft Gelatin Capsules Formulations-Identification,
Synthesis and Liquid Chromatography Separation of the Degradation Products.
AB - Unknown impurities were identified in ibuprofen (IBU) soft gelatin capsules
(SGCs) during long-term stability testing by a UHPLC method with UV detection and
its chemical formula was determined using high resolution/accurate mass (HRAM) LC
MS. Reference standards of the impurities were subsequently synthesized, isolated
by semi-preparative HPLC and characterized using HRAM LC-MS, NMR and IR. Two
impurities were formed by esterification of IBU with polyethylene glycol (PEG),
which is used as a fill of the SGCs, and were identified as IBU-PEG monoester and
IBU-PEG diester. Two other degradants arised from reaction of IBU with sorbitol
and sorbitan, which are components of the shell and serves as plasticizers. Thus,
IBU sorbitol monoester (IBU-sorbitol) and IBU sorbitan monoester (IBU-sorbitan
ester) were identified. An UHPLC method was further optimized in order to
separate, selectively detect and quantify the degradation products in IBU SGCs.
PMID- 28505278
TI - Cost-effectiveness of outpatient parenteral antibiotic therapy: a simulation
modelling approach.
AB - Objectives: In the UK, patients who require intravenous antimicrobial (IVA)
treatment may receive this in the community through outpatient parenteral
antimicrobial therapy (OPAT) services. Services include: IVA administration at a
hospital outpatient clinic (HO); IVA administration at home by a general nurse
(GN) or a specialist nurse (SN); or patient self-administered (SA) IVA
administration following training. There is uncertainty regarding which OPAT
services represent value for money; this study aimed to estimate their cost
effectiveness. Methods: A cost-effectiveness decision-analytic model was
developed using a simulation technique utilizing data from hospital records and a
systematic review of the literature. The model estimates cost per QALY gained
from the National Health Service (NHS) perspective for short- and long-term
treatment of infections and service combinations across these. Results: In short
term treatments, HO was estimated as the most effective (0.7239 QALYs), but at
the highest cost (L973). SN was the least costly (L710), producing 0.7228 QALYs.
The combination between SN and HO was estimated to produce 0.7235 QALYs at a cost
of L841. For long-term treatments, SN was the most effective (0.677 QALYs),
costing L2379, while SA was the least costly at L1883, producing 0.666 QALYs. A
combination of SA and SN was estimated to produce 0.672 QALYs at a cost of L2128.
Conclusions: SN and SA are cost-effective for short- and long-term treatment of
infections, while combining services may represent the second-best alternative
for OPAT in the UK.
PMID- 28505280
TI - Mining e-cigarette adverse events in social media using Bi-LSTM recurrent neural
network with word embedding representation.
AB - Objective: Recent years have seen increased worldwide popularity of e-cigarette
use. However, the risks of e-cigarettes are underexamined. Most e-cigarette
adverse event studies have achieved low detection rates due to limited subject
sample sizes in the experiments and surveys. Social media provides a large data
repository of consumers' e-cigarette feedback and experiences, which are useful
for e-cigarette safety surveillance. However, it is difficult to automatically
interpret the informal and nontechnical consumer vocabulary about e-cigarettes in
social media. This issue hinders the use of social media content for e-cigarette
safety surveillance. Recent developments in deep neural network methods have
shown promise for named entity extraction from noisy text. Motivated by these
observations, we aimed to design a deep neural network approach to extract e
cigarette safety information in social media. Methods: Our deep neural language
model utilizes word embedding as the representation of text input and recognizes
named entity types with the state-of-the-art Bidirectional Long Short-Term Memory
(Bi-LSTM) Recurrent Neural Network. Results: Our Bi-LSTM model achieved the best
performance compared to 3 baseline models, with a precision of 94.10%, a recall
of 91.80%, and an F-measure of 92.94%. We identified 1591 unique adverse events
and 9930 unique e-cigarette components (ie, chemicals, flavors, and devices) from
our research testbed. Conclusion: Although the conditional random field baseline
model had slightly better precision than our approach, our Bi-LSTM model achieved
much higher recall, resulting in the best F-measure. Our method can be
generalized to extract medical concepts from social media for other medical
applications.
PMID- 28505281
TI - Application of Partially Substituted 3,5-Dimethylphenylcarbamate-(3-(2-O-beta
Cyclodextrin)-2-Hydroxypropoxy)-Propylsilyl-Appended Silica Particles as Chiral
Stationary Phase for Multi-mode High-performance Liquid Chromatography.
AB - A new type of partially substituted 3,5-dimethylphenylcarbamate-(3-(2-O-beta
cyclodextrin)-2-hydroxypropoxy)-propylsilyl-appended silica particles (MP-CD-HPS)
have been prepared by a convenient post-immobilization derivazition procedure.
The MP-CD-HPS has been successfully used as chiral stationary phase (CSP) for
high-performance liquid chromatography (HPLC) under normal phase, reversed phase
and polar organic mobile phase conditions. The chromatographic evaluation results
show that the MP-CD-HPS has excellent selectivity for the separation of aromatic
positional isomers and enantiomers of some chiral compounds. The multi-mode HPLC
separation results also indicate that both the stable ether spacer linking to the
wider torus rim of beta-cyclodextrin in the MP-CD-HPS phase and the hydroxyl
residues in the partially substituted beta-cyclodextrin have important
contributions to chiral recognitions and chromatographic separations.
PMID- 28505282
TI - Survival and Locomotory Behavior of Earwigs After Exposure to Reduced-Risk
Insecticides.
AB - The conservation of natural enemies is an important tactic to promote biological
control of arthropod pests. The earwig Doru luteipes (Sccuder) is the most
important predator of the fall armyworm Spodoptera frugiperda (J.E. Smith) in
corn fields. One way of conserving these predators in the field is by using only
selective insecticides when the pest population reaches the economic threshold.
Some recent insecticides such as azadirachtin, chlorantraniliprole, and novaluron
have been claimed to pose reduced risk for natural enemies. Nevertheless, there
is a dearth of information regarding the selectivity of these insecticides upon
earwigs in specific. In this study, we carried out a series of laboratory assays
to examine the survivorship and locomotory behavior of D. luteipes after exposure
to fresh dry residue of azadirachtin, chlorantraniliprole, and novaluron. Our
results show a significant survival reduction for D. luteipes nymphs exposed to
fresh residues of chlorantraniliprole and novaluron. In the behavioral studies,
adults of D. luteipes stopped more often, spent more time resting (inactive), and
moved more slowly immediately after exposure to chlorantraniliprole residue.
These results suggest that chlorantraniliprole may mediate an impaired movement
and a behavior arrestment of earwigs after contact with this insecticide fresh
residue. This could translate into reduced foraging efficiency, and increase
exposure and insecticide uptake. Although chlorantraniliprole and novaluron
showed a potential to undermine the biological control provided by earwigs, it is
yet essential to conduct field trials in order to confirm our laboratory results.
PMID- 28505279
TI - Somatic USP8 Gene Mutations Are a Common Cause of Pediatric Cushing Disease.
AB - Context: Somatic mutations in the ubiquitin-specific protease 8 (USP8) gene have
been recently identified as the most common genetic alteration in patients with
Cushing disease (CD). However, the frequency of these mutations in the pediatric
population has not been extensively assessed. Objective: We investigated the
status of the USP8 gene at the somatic level in a cohort of pediatric patients
with corticotroph adenomas. Design and Methods: The USP8 gene was fully sequenced
in both germline and tumor DNA samples from 42 pediatric patients with CD.
Clinical, biochemical, and imaging data were compared between patients with and
without somatic USP8 mutations. Results: Five different USP8 mutations (three
missense, one frameshift, and one in-frame deletion) were identified in 13
patients (31%), all of them located in exon 14 at the previously described
mutational hotspot, affecting the 14-3-3 binding motif of the protein. Patients
with somatic mutations were older at disease presentation [mean 5.1 +/- 2.1
standard deviation (SD) vs 13.1 +/- 3.6 years, P = 0.03]. Levels of urinary free
cortisol, midnight serum cortisol, and adrenocorticotropic hormone, as well as
tumor size and frequency of invasion of the cavernous sinus, were not
significantly different between the two groups. However, patients harboring
somatic USP8 mutations had a higher likelihood of recurrence compared with
patients without mutations (46.2% vs 10.3%, P = 0.009). Conclusion: Somatic USP8
gene mutations are a common cause of pediatric CD. Patients harboring a somatic
mutation had a higher likelihood of tumor recurrence, highlighting the potential
importance of this molecular defect for the disease prognosis and the development
of targeted therapeutic options.
PMID- 28505283
TI - Oxidative Injury and Iron Redistribution Are Pathological Hallmarks of Marmoset
Experimental Autoimmune Encephalomyelitis.
AB - Oxidative damage and iron redistribution are associated with the pathogenesis and
progression of multiple sclerosis (MS), but these aspects are not entirely
replicated in rodent experimental autoimmune encephalomyelitis (EAE) models.
Here, we report that oxidative burst and injury as well as redistribution of iron
are hallmarks of the MS-like pathology in the EAE model in the common marmoset.
Active lesions in the marmoset EAE brain display increased expression of
nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p22phox, p47phox,
and gp91phox) and inducible nitric oxide synthase immunoreactivity within lesions
with active inflammation and demyelination, coinciding with enhanced expression
of mitochondrial heat-shock protein 70 and superoxide dismutase 1 and 2. The EAE
lesion-associated liberation of iron (due to loss of iron-containing myelin) was
associated with altered expression of the iron metabolic markers FtH1,
lactoferrin, hephaestin, and ceruloplasmin. The enhanced expression of oxidative
damage markers in inflammatory lesions indicates that the enhanced antioxidant
enzyme expression could not counteract reactive oxygen and nitrogen species
induced cellular damage, as is also observed in MS brains. This study
demonstrates that oxidative injury and aberrant iron distribution are prominent
pathological hallmarks of marmoset EAE thus making this model suitable for
therapeutic intervention studies aimed at reducing oxidative stress and
associated iron dysmetabolism.
PMID- 28505285
TI - Defining Pediatric Diarrhea in Low-Resource Settings.
AB - Differences in definitions of acute pediatric diarrhea result in variable
estimates of morbidity and mortality, treatment coverage, and associations with
risk factors and outcomes. We reviewed published literature and guidelines
focused on acute pediatric diarrhea in low- and middle-income countries. Clinical
guidelines most commonly defined diarrhea in terms of quantity of loose or watery
stool with consideration of normal stool patterns, whereas research studies often
relied exclusively on a quantitative definition. The most commonly used
quantitative definition, >=3 loose or watery stools in a 24-hour period, has been
compared to gold standards of caregiver perception and visual inspection of
stool, with variable agreement. Age, breast-feeding status, and setting (facility
vs household-based) influence the performance of quantitative diarrhea
definitions in children. Universal adoption of a set of valid gold standard
definitions specifically aligned with various programmatic and research goals
will lead to more accurate coverage estimates and better-informed resource
prioritization.
PMID- 28505284
TI - Pathogenic Anti-Mullerian Hormone Variants in Polycystic Ovary Syndrome.
AB - Context: Polycystic ovary syndrome (PCOS), a common endocrine condition, is the
leading cause of anovulatory infertility. Objective: Given that common disease
susceptibility variants account for only a small percentage of the estimated PCOS
heritability, we tested the hypothesis that rare variants contribute to this
deficit in heritability. Design, Setting, and Participants: Unbiased whole-genome
sequencing (WGS) of 80 patients with PCOS and 24 reproductively normal control
subjects identified potentially deleterious variants in AMH, the gene encoding
anti-Mullerian hormone (AMH). Targeted sequencing of AMH of 643 patients with
PCOS and 153 control patients was used to replicate WGS findings. Main Outcome
Measures: Dual luciferase reporter assays measured the impact of the variants on
downstream AMH signaling. Results: We found 24 rare (minor allele frequency <
0.01) AMH variants in patients with PCOS and control subjects; 18 variants were
specific to women with PCOS. Seventeen of 18 (94%) PCOS-specific variants had
significantly reduced AMH signaling, whereas none of 6 variants observed in
control subjects showed significant defects in signaling. Thus, we identified
rare AMH coding variants that reduced AMH-mediated signaling in a subset of
patients with PCOS. Conclusion: To our knowledge, this study is the first to
identify rare genetic variants associated with a common PCOS phenotype. Our
findings suggest decreased AMH signaling as a mechanism for the pathogenesis of
PCOS. AMH decreases androgen biosynthesis by inhibiting CYP17 activity; a
potential mechanism of action for AMH variants in PCOS, therefore, is to increase
androgen biosynthesis due to decreased AMH-mediated inhibition of CYP17 activity.
PMID- 28505287
TI - Anti-Helicobacter pylori activity of non-living, heat-killed form of lactobacilli
including Lactobacillus johnsonii No.1088.
AB - Some strains of lactic acid bacteria are reported to inhibit the growth of
Helicobacter pylori and proposed to be useful to support so-called triple therapy
for H. pylori. Although most strains must be alive to exert their anti-H. pylori
activity, some lactobacilli strains are effective even when dead. One possible
underlying mechanism of such an activity of non-living lactobacilli is reportedly
co-aggregation with H. pylori. In this study, we found that a non-living heat
killed form of Lactobacillus johnsonii No.1088 (HK-LJ88) and also that of some
other lactobacilli inhibited the growth of H. pylori in vitro. Furthermore, the
number of H. pylori in the infected stomach of germ-free mice was significantly
decreased by the repeated oral administration of HK-LJ88. Observation by scanning
electron microscopy revealed that no co-aggregation had occurred between H.
pylori and HK-LJ88; instead, deformations of H. pylori (e.g. disappearance of
spiral, bending of cell body, coccoid formation, degradations, etc.) appeared
after incubation for 24 h with HK-LJ88. These results suggest that HK-LJ88
inhibited H. pylori activity probably not by co-aggregation but by some unknown
mechanism involving HK-LJ88's cell surface molecules and that even non-living
lactobacilli are possibly useful to support H. pylori eradication therapy.
PMID- 28505288
TI - Effect of different antibiotics on biofilm produced by uropathogenic Escherichia
coli isolated from children with urinary tract infection.
AB - Recurrent urinary tract infections (UTIs) occur frequently in children and women.
Intracellular bacterial communities (IBCs) and biofilm formation by Escherichia
coli are risk factors for recurrence. The aim of this study was to evaluate the
effect of different antibiotics on biofilms by E. coli strains isolated from
children with UTI and to correlate virulence factors and IBCs with biofilm
formation. A total of 116 E. coli strains were tested for biofilm formation using
the crystal violet microplate technique. 58.6% of the strains did not produce
biofilm, while 16.4%, 18.1% and 6.8% formed weak, moderate and strong biofilms,
respectively. No correlation was found between the ability to form biofilms and
the presence of IBCs. Biofilm formation was significantly associated with pili P
codifying genes, whereas other virulence factors were not statistically
associated. Antibiotics, including ampicillin, cephalothin, ceftriaxone,
ceftazidime, amikacin and ciprofloxacin, were evaluated at different
concentrations after 48 h of biofilm formation. Except ampicillin, the other
antibiotics tested induced a significant reduction of biofilm biomass. In the
case of recurrent UTIs potentially associated with the presence of biofilm, the
use of third-generation cephalosporin, fluoroquinolones and aminoglycosides could
be recommended. These antibiotics demonstrated to reduce biofilm biomass produced
even by resistant strains.
PMID- 28505286
TI - PIXiE: an algorithm for automated ion mobility arrival time extraction and
collision cross section calculation using global data association.
AB - Motivation: Drift tube ion mobility spectrometry coupled with mass spectrometry
(DTIMS-MS) is increasingly implemented in high throughput omics workflows, and
new informatics approaches are necessary for processing the associated data. To
automatically extract arrival times for molecules measured by DTIMS at multiple
electric fields and compute their associated collisional cross sections (CCS), we
created the PNNL Ion Mobility Cross Section Extractor (PIXiE). The primary
application presented for this algorithm is the extraction of data that can then
be used to create a reference library of experimental CCS values for use in high
throughput omics analyses. Results: We demonstrate the utility of this approach
by automatically extracting arrival times and calculating the associated CCSs for
a set of endogenous metabolites and xenobiotics. The PIXiE-generated CCS values
were within error of those calculated using commercially available instrument
vendor software. Availability and implementation: PIXiE is an open-source tool,
freely available on Github. The documentation, source code of the software, and a
GUI can be found at https://github.com/PNNL-Comp-Mass-Spec/PIXiE and the source
code of the backend workflow library used by PIXiE can be found at
https://github.com/PNNL-Comp-Mass-Spec/IMS-Informed-Library . Contact:
erin.baker@pnnl.gov or thomas.metz@pnnl.gov. Supplementary information:
Supplementary data are available at Bioinformatics online.
PMID- 28505289
TI - Financial and environmental costs of reusable and single-use anaesthetic
equipment.
AB - Background.: An innovative approach to choosing hospital equipment is to consider
the environmental costs in addition to other costs and benefits. Methods.: We
used life cycle assessment to model the environmental and financial costs of
different scenarios of replacing reusable anaesthetic equipment with single-use
variants. The primary environmental costs were CO 2 emissions (in CO 2
equivalents) and water use (in litres). We compared energy source mixes between
Australia, the UK/Europe, and the USA. Results.: For an Australian hospital with
six operating rooms, the annual financial cost of converting from single-use
equipment to reusable anaesthetic equipment would be an AUD$32 033 (L19 220), 46%
decrease. In Australia, converting from single-use to reusable equipment would
result in an increase of CO 2 emissions from 5095 (95% CI: 4614-5658) to 5575 kg
CO 2 eq (95% CI: 5542-5608), a 480 kg CO 2 eq (9%) increase. Using the
UK/European power mix, converting from single-use (5575 kg CO 2 eq) to reusable
anaesthetic equipment (802 kg CO 2 eq) would result in an 84% reduction (4873 kg
CO 2 eq) in CO 2 emissions, whilst in the USA converting to reusables would have
led to a 2427 kg CO 2 eq (48%) reduction. In Australia, converting from single
use to reusable equipment would more than double water use from 34.4 to 90.6
kilolitres. Conclusions.: For an Australian hospital with six operating rooms,
converting from single-use to reusable anaesthetic equipment saved more than
AUD$30 000 (L18 000) per annum, but increased the CO 2 emissions by almost 10%.
The CO 2 offset is highly dependent on the power source mix, while water
consumption is greater for reusable equipment.
PMID- 28505292
TI - Effect of Auricular Point Acupressure on Axial Neck Pain After Anterior Cervical
Discectomy and Fusion: A Randomized Controlled Trial.
AB - Objectives: To evaluate the effect of auricular point acupressure (APA) on axial
neck pain after anterior cervical discectomy and fusion (ACDF) surgery. Design: A
prospective randomized controlled trial was performed. Subjects and setting:
Twenty-nine participants were randomly divided into two groups, real or sham APA.
Participants were enrolled from Shaoxing Hospital of Traditional Chinese
Medicine, affiliated with Zhejiang Chinese Medical University. Methods: Eligible
participants received a four-week real or sham APA treatment according to their
assigned groups. The clinical outcomes were assessed by the criteria of Hosono et
al., the Brief Pain Inventory Short Form (BPI), and the 36-item Short Form Health
Survey (SF-36). In addition, plasma interleukin (IL)-1beta, IL-6, and tumor
necrosis factor (TNF)-alpha were analyzed. Results: Patients with severe or
moderate axial neck pain accounted for 28.6% and 35.7% in the real APA group at
the end of treatment and one-month follow-up. BPI scores were decreased in the
real APA group at the end of treatment and one-month follow-up. The total mean
score of SF-36 was improved in the real APA group and significantly higher than
in the sham APA group. Additional, the levels of IL-1beta, IL-6, and TNF-alpha
were decreased in the real APA group. Conclusions: The findings supported the
therapeutic effect of APA treatment on axial neck pain after ACDF surgery, and
they exert the possible therapeutic effect on downregulating the levels of plasma
IL-1beta, IL-6, and TNF-alpha.
PMID- 28505290
TI - Supraphysiologic estradiol is an independent predictor of low birth weight in
full-term singletons born after fresh embryo transfer.
AB - STUDY QUESTION: Is supraphysiologic estradiol (E2) an independent predictor of
low birth weight (LBW) in singletons born after fresh IVF-embryo transfer (ET)
cycles? SUMMARY ANSWER: Our results suggest that E2 > 2500 pg/ml is an
independent predictor for LBW in full-term singletons born to normal responder
patients undergoing fresh IVF-ET cycles. WHAT IS KNOWN ALREADY: The pathogenesis
of LBW in IVF singletons remains unknown. However, recent studies have suggested
that the hyperestrogenic milieu generated during ovarian stimulation may create a
sub-optimal peri-implantation environment, leading to placental dysfunction, and
therefore, LBW. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study of
normal responder patients, <40 years old, undergoing fresh IVF-ET cycles
resulting in live singleton births between January 2005 and June 2014.
PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 6419 patients had live
births after fresh IVF-ET during the study period, of which 2348 (36.6%) patients
were excluded due to multiple gestation, vanishing twins or incomplete records.
Perinatal outcomes recorded for all patients included birth weight, gestational
age (GA) at delivery, mode of delivery and gender. Term birth, preterm birth
(PTB) and LBW incidence proportions were plotted against E2 level on the day of
trigger. The term LBW incidence proportion (i.e. singletons born at GA >= 37
weeks with birth weight <2500 g) was considered the primary outcome of interest.
MAIN RESULTS AND THE ROLE OF CHANCE: A total of 4071 patients with live singleton
births were included. The median age, BMI, E2 level and birth weight for the
study cohort was 36 (33-39) years, 22.3 (20.4-25.0) kg/m2, 1554 (1112.7-2179)
pg/ml and 3289 (2920-3628) g, respectively. The incidence proportion of LBW rose
from 6.4% (E2 2001-2500 pg/ml) to 20.7% (E2 3501-4000 pg/ml), without a
corresponding rise in the incidence proportion of PTB. The odds of term LBW with
E2 > 2500 pg/ml were 6.1-7.9 times higher compared to the referent E2 group.
Multivariable logistic regression analysis revealed that E2 was an independent
predictor for term LBW, even after adjusting for age, BMI, race, parity,
infertility diagnosis, duration of ovarian stimulation, gonadotropin dosage and
method of insemination (adjusted odds ratio 10.8, 95% CI 9.2-12.5). Receiver
operating characteristic analysis generated an AUC estimate of 0.85 for E2 level
as a predictor of LBW. LIMITATIONS REASONS FOR CAUTION: The current study did not
include analyses of hypertensive disorders of pregnancy or placental
abnormalities. Furthermore, all patients were normal responders and of normal
BMI, possibly limiting the overall generalizability of the study. Finally, as
with any retrospective study, prospective data are required to validate the role
of E2 in predicting LBW. WIDER IMPLICATIONS OF THE FINDINGS: Our results
emphasize the importance of minimizing the supraphysiologic elevations of E2
levels during ovarian stimulation in fresh IVF-ET cycles. This, in turn, can
optimize the early peri-implantation environment and mitigate adverse perinatal
outcomes such as LBW. STUDY FUNDING/COMPETING INTEREST(S): Dr Paul J. Christos
was partially supported by the following grant: Clinical and Translational
Science Center at Weill Cornell Medical College (UL1-TR000457-06). TRIAL
REGISTRATION NUMBER: N/A.
PMID- 28505293
TI - Budesonide MMX in Paediatric Patients With Ulcerative Colitis.
PMID- 28505291
TI - Comparison of the Simplified sWHI and the Standard CHS Frailty Phenotypes for
Prediction of Mortality, Incident Falls, and Hip Fractures in Older Women.
AB - Background: We compared the simplified Women's Health Initiative (sWHI) and the
standard Cardiovascular Health Study (CHS) frailty phenotypes in predicting
falls, hip fracture, and death in older women. Methods: Participants are from the
WHI Clinical Trial. CHS frailty criteria included weight loss, exhaustion,
weakness, slowness, and low physical activity. The sWHI frailty score used two
items from the RAND-36 physical function and vitality subscales, one item from
the WHI physical activity scale plus the CHS weight loss criteria. Specifically,
level of physical function was the capacity to walk one block and scored as
severe (2-points), moderate (1-point), or no limitation (0). Vitality was based
on feeling tired most or all of the time (1-point) versus less often (0). Low
physical activity was walking outside less than twice a week (1-point) versus
more often (0). A total score of 3 resulted in a frailty classification, a score
of 1 or 2 defined pre-frailty, and 0 indicated nonfrailty. Outcomes were modeled
using Cox regression and Harrell C-statistics were used for comparisons. Results:
Approximately 5% of the participants were frail based on the CHS or sWHI
phenotype. The sWHI frailty phenotype was associated with higher rates of
mortality (hazard ratio [HR] = 2.36, p <= .001) and falls (HR = 1.45, p = .005).
Comparable HRs in CHS-phenotype were 1.97 (p < .001) and 1.36 (p = .03),
respectively. Neither phenotype predicted hip fracture. Harrell C-statistics
revealed nonsignificant differences in HRs between the CHS and sWHI frailty
phenotypes. Conclusion: The sWHI phenotype, which is self-reported and brief,
might be practical in settings with limited resources.
PMID- 28505294
TI - Anticalcification effect of a combination of decellularization, organic solvents
and amino acid detoxification on glutaraldehyde-fixed xenopericardial heart
valves in a large-animal long-term circulatory model.
AB - OBJECTIVES: We aimed to investigate the effect of a combination of
anticalcification treatments, which were effective for preventing calcification
in a small animal experiment, on glutaraldehyde-fixed xenopericardial valves
using a large-animal long-term circulatory model. METHODS: Valved conduits were
made of porcine pericardium as a leaflet and bovine pericardium as a conduit and
were implanted into the right ventricular outflow tract of goats under
cardiopulmonary bypass. The goats were divided into study (glutaraldehyde +
combined anticalcification treatment, n = 6) and control (glutaraldehyde alone, n
= 9) groups. Upon euthanization at 1 year, echocardiography and cardiac
catheterization were performed. Explanted tissues were microscopically examined
and analysed for measuring the calcium content. RESULTS: Haemodynamic data were
obtained from 3 and 2 goats in the study and control groups, respectively. All
valves, except 1, which was limited in motion, were functioning well on
echocardiography; pressure gradients across the right ventricular outflow tract
were lower in the study group on cardiac catheterization. On gross inspection,
all leaflets remained mobile without calcific deposits in the study group, while
most leaflets were heavily calcified in the control group. The calcium content in
the leaflets remained low (<=4 ug/mg) in the study group. Among the leaflets
explanted from goats that survived longer (>3 months), the calcium concentration
was higher in the control group than in the study group [15.1 ug/mg (n = 5) vs
2.7 ug/mg (n = 5), respectively; P = 0.008). CONCLUSIONS: Porcine pericardial
leaflets treated with our anticalcification protocol showed better function and
less calcification than those treated with glutaraldehyde alone in the pulmonary
position.
PMID- 28505295
TI - Phylogenetic distribution of tir-cytoskeleton coupling protein (tccP and tccP2)
genes in atypical enteropathogenic Escherichia coli.
AB - Enteropathogenic Escherichia coli (EPEC) strains employ the type III secretion
system (T3SS) effector Tir to induce actin cytoskeletal rearrangements. While
some EPEC require tyrosine phosphorylation (Y-P) of Tir to trigger actin
assembling, certain strains whose Tir is not tyrosine phosphorylated utilize the
T3SS effector Tir-cytoskeleton coupling protein (TccP/TccP2) for efficient actin
polymerization. The presence of tccP/tccP2 in typical EPEC belonging to distinct
evolutionary lineages is well established but, in contrast, little is known about
the distribution of these genes in atypical EPEC (aEPEC) showing distinct
phylogenetic background. In this study, we screened 72 pathogenic aEPEC for the
presence of tccP/tccP2 genes, and further characterized positive strains
regarding tir type, phylogroups and production of TccP/TccP2. The tccP and/or
tccP2 genes were detected in 45.8% of the strains, with a predominance of tccP2
allele. Most of these strains carried tirY-P, suggesting that can trigger actin
polymerization using both Tir tyrosine phosphorylation and TccP/TccP2 pathways.
aEPEC strains carrying tccP or tccP2 were significantly associated to phylogroups
E and B1, respectively. We also observed a strain-to-strain variation regarding
TccP/TccP2 production. Our results demonstrate a wide distribution of tccP/tccP2
genes among pathogenic aEPEC strains, as well associations between specific
alleles and phylogenetic backgrounds.
PMID- 28505297
TI - Reply to Jones et al.
PMID- 28505296
TI - Varenicline is associated with a modest limitation in weight gain in smokers
after smoking cessation: a meta-analysis.
AB - Objective: To assess the effect of treatment on limiting weight gain in
abstainers using and not using varenicline and during the nontreatment phase.
Methods: The PubMed, Medline, EMBASE and Cochrane Library databases were searched
to identify relevant studies published in English or Chinese. A meta-analysis was
performed to calculate pooled weighted mean differences (WMDs) in weight gain in
smokers after smoking cessation between varenicline and control groups and their
corresponding 95% CIs. The I2 statistic was used to measure heterogeneity.
Publication bias was evaluated using Egger's regression asymmetry test. Results:
A total of 10 studies were included. The WMD in weight gain in abstainers between
varenicline and control groups was -0.23 kg (95% CI: -0.36 to -0.09, P < 0.05).
Moreover, the result of the subgroup analysis by timepoint of weight measurement
indicated that the WMD in weight gain in smokers after smoking cessation between
varenicline and control groups after the 12-week treatment phase was -0.23 kg
(95% CI: -0.37 to -0.08, P < 0.05), and the WMD observed during the nontreatment
follow-up phase was -0.69 kg (95% CI: -2.15 to 0.77, P > 0.05). In addition, the
result of the subgroup analysis by type of control showed that the WMD in weight
gain in abstainers from smoking between the varenicline and placebo groups was
0.29 kg (95% CI: -0.46 to -0.12, P < 0.05), and the WMD between the varenicline
and other control groups was -0.20 kg (95% CI: -0.77 to 0.37, P > 0.05).
Conclusion: Varenicline was associated with a modest limitation in weight gain in
smokers after smoking cessation; however, the impact of varenicline use was not
long-term, and, in fact, no different from that of the placebo treatment.
PMID- 28505298
TI - Early health outcome and 10-year survival in patients undergoing redo coronary
surgery with or without cardiopulmonary bypass: a propensity score-matched
analysis.
AB - OBJECTIVES: To investigate the in-hospital health outcome and 10-year survival in
patients undergoing redo coronary surgery with (redo-CABG) or without (redo
OPCAB) cardiopulmonary bypass. METHODS: A total of 349 redo coronary surgery
patients were identified from our registry. Of these, 143 redo-OPCAB patients
(40.97%) were compared with 206 redo-CABG patients. To minimize the bias, we also
conducted propensity score matching. In Matched Analysis A, 111 redo-OPCAB
patients with any type of primary cardiac operation were compared with 111 redo
CABG cases. In Matched Analysis B, 84 redo-OPCAB patients with isolated coronary
surgery as their primary operation were compared with 84 redo-CABG patients. We
assessed for all 3 analyses a composite of in-hospital mortality, acute kidney
injury, stroke and severe low cardiac output requiring intra-aortic balloon pump.
In addition, we assessed 1-, 5-, and 10-year survival. RESULTS: In the unmatched
analysis, redo-CABG was associated with higher usage of intra-aortic balloon pump
(10 vs 3%, P = 0.01) and composite compared with redo-OPCAB (25 vs 16%, P = 0.06)
and similar 10-year survival (67.2 vs 68.5%, log-rank test: P = 0.78). Matched
Analysis A showed similar rates of composite (15 vs 21%, P = 0.25) and 10-year
survival (65.1 vs 60.8%, log-rank test: P = 0.5). Matched Analysis B showed
reduction of the composite (19 vs 8%, P = 0.04), less in-hospital mortality (5 vs
0%, P = 0.13), 4.5 times less need for intra-aortic balloon pump (2 vs 11%, P =
0.02) favouring redo-OPCAB and a similar 10-year survival (71.6 vs 71.7%, log
rank test: P = 0.61). CONCLUSIONS: Redo-OPCAB surgery is feasible, safe and
effective with improved in-hospital outcome and similar 10-year survival compared
to redo-CABG.
PMID- 28505299
TI - Measuring vaccination coverage better will help achieve disease control.
AB - Timely and accurate measurement of vaccination coverage is required to evaluate
the success of vaccine programmes as well as identifying susceptible groups in
order to better control disease. Estimating coverage requires knowledge of how
many people are eligible for vaccination, and how many have received the vaccine.
Achieving this presents a number of challenges in both high and low income
settings. Investing in systems that record vaccination coverage better, as an
integral part of vaccine strategies, will be a step towards better control of
vaccine-preventable diseases.
PMID- 28505300
TI - Impact of glutathione metabolism on zinc homeostasis in Saccharomyces cerevisiae.
AB - Zinc is a crucial mineral for all organisms as it is an essential cofactor for
the proper function of a plethora of proteins and depletion of zinc causes
oxidative stress. Glutathione is the major redox buffering agent in the cell and
therefore important for mitigation of the adverse effects of oxidative stress. In
mammalian cells, zinc deficiency is accompanied by a glutathione depletion. In
the yeast Saccharomyces cerevisiae, the opposite effect is observed: under low
zinc conditions, an elevated glutathione concentration is found. The main
regulator to overcome zinc deficiency is Zap1p. However, we show that Zap1p is
not involved in this glutathione accumulation phenotype. Furthermore, we found
that in glutathione-accumulating strains also the metal ion-binding phytochelatin
2, which is an oligomer of glutathione, is accumulated. This increased
phytochelatin concentration correlates with a lower free zinc level in the
vacuole. These results suggest that phytochelatin is important for zinc buffering
in S. cerevisiae and thus explains how zinc homeostasis is connected with
glutathione metabolism.
PMID- 28505301
TI - Two New Species of the Simulium (Simulium) variegatum Species-Group of Black
Flies (Diptera: Simuliidae) From Thailand.
AB - Two new species of black flies, Simulium (Simulium) srisukai and S. (S.)
kiewmaepanense, are described from specimens collected in Thailand. Both species
are assigned to the Simulium variegatum species-group of the subgenus Simulium
(Simulium) Latreille. They are characterized by the darkened female femora and
tibiae and six inflated pupal gill filaments, and the darkened female tibiae and
six ordinary thread-like pupal gill filaments, respectively. Taxonomic notes are
given to separate these new species from 10 related species among the group.
These new species represent the third and fourth species of the S. variegatum
species-group from Thailand.
PMID- 28505302
TI - The Whole-Genome and Transcriptome of the Manila Clam (Ruditapes philippinarum).
AB - The manila clam, Ruditapes philippinarum, is an important bivalve species in
worldwide aquaculture including Korea. The aquaculture production of R.
philippinarum is under threat from diverse environmental factors including
viruses, microorganisms, parasites, and water conditions with subsequently
declining production. In spite of its importance as a marine resource, the
reference genome of R. philippinarum for comprehensive genetic studies is largely
unexplored. Here, we report the de novo whole-genome and transcriptome assembly
of R. philippinarum across three different tissues (foot, gill, and adductor
muscle), and provide the basic data for advanced studies in selective breeding
and disease control in order to obtain successful aquaculture systems. An
approximately 2.56 Gb high quality whole-genome was assembled with various
library construction methods. A total of 108,034 protein coding gene models were
predicted and repetitive elements including simple sequence repeats and noncoding
RNAs were identified to further understanding of the genetic background of R.
philippinarum for genomics-assisted breeding. Comparative analysis with the
bivalve marine invertebrates uncover that the gene family related to complement
C1q was enriched. Furthermore, we performed transcriptome analysis with three
different tissues in order to support genome annotation and then identified
41,275 transcripts which were annotated. The R. philippinarum genome resource
will markedly advance a wide range of potential genetic studies, a reference
genome for comparative analysis of bivalve species and unraveling mechanisms of
biological processes in molluscs. We believe that the R. philippinarum genome
will serve as an initial platform for breeding better-quality clams using a
genomic approach.
PMID- 28505303
TI - Acute Effects of Aerobic Exercise on Affect and Smoking Craving in the Weeks
Before and After a Cessation Attempt.
AB - Introduction: Aerobic exercise may improve smoking abstinence via reductions in
craving and negative affect and increases in positive moods. Acute changes in
craving and affect before and after structured exercise sessions have not been
examined during the weeks prior to and following quit attempts nor has smoking
status been examined in relation to these effects. Given that regular cigarette
smoking can be perceived as affect enhancing and craving reducing, it is not
known whether exercise could contribute additional affective benefit beyond these
effects. Method: Participants (N = 57; 68.4% women) were low-active daily smokers
randomized to cessation treatments plus either group-based aerobic exercise (AE)
or a health-education control (HEC). Mood, anxiety, and craving were assessed
before and after each intervention session for each of the 12 weeks. Carbon
monoxide (CO) breath samples <= 5ppm indicated smoking abstinence. Results:
During the prequit sessions, significantly greater decreases in anxiety following
AE sessions relative to HEC sessions were observed. Changes in mood and craving
were similar after AE and HEC sessions prior to quitting. Postquit attempt,
significant reductions in craving and anxiety were observed after AE sessions but
not following HEC. During the postquit period, positive mood increased following
AE sessions relative to HEC only among individuals who were abstinence on that
day. Conclusions: AE may be effective in acutely reducing anxiety prior to a quit
attempt and both anxiety and craving following the quit attempt regardless of
abstinence status. The mood-enhancing effects of AE may occur only in the context
of smoking abstinence. Implications: The current findings underscore the
importance of examining the acute effects of aerobic exercise prior to and after
a cessation attempt and as a function of smoking status. Given the equivocal
results from previous studies on the efficacy of exercise for smoking cessation,
increasing our understanding of how aerobic exercise produces its reinforcing
benefits for smokers attempting to quit could potentially inform the refinement
(e.g., timing/sequencing) of exercise interventions within smoking cessation
programs.
PMID- 28505304
TI - Phytoplasma-conserved phyllogen proteins induce phyllody across the Plantae by
degrading floral MADS domain proteins.
AB - ABCE-class MADS domain transcription factors (MTFs) are key regulators of floral
organ development in angiosperms. Aberrant expression of these genes can result
in abnormal floral traits such as phyllody. Phyllogen is a virulence factor
conserved in phytoplasmas, plant pathogenic bacteria of the class Mollicutes. It
triggers phyllody in Arabidopsis thaliana by inducing degradation of A- and E
class MTFs. However, it is still unknown whether phyllogen can induce phyllody in
plants other than A. thaliana, although phytoplasma-associated phyllody symptoms
are observed in a broad range of angiosperms. In this study, phyllogen was shown
to cause phyllody phenotypes in several eudicot species belonging to three
different families. Moreover, phyllogen can interact with MTFs of not only
angiosperm species including eudicots and monocots but also gymnosperms and a
fern, and induce their degradation. These results suggest that phyllogen induces
phyllody in angiosperms and inhibits MTF function in diverse plant species.
PMID- 28505305
TI - Efficacy and Safety of Ledipasvir/Sofosbuvir for the Treatment of Chronic
Hepatitis C in Persons With Sickle Cell Disease.
AB - Patients with sickle cell disease are at high risk for chronic hepatitis C
infection. Prior treatment has been limited due to the use of ribavirin causing
hemolytic anemia and interferon causing cytopenias. We demonstrate the safety and
efficacy of fixed-dose combination ledipasvir and sofosbuvir for 12 weeks in this
population.
PMID- 28505307
TI - Sexual Dimorphism and Retinal Mosaic Diversification following the Evolution of a
Violet Receptor in Butterflies.
AB - Numerous animal lineages have expanded and diversified the opsin-based
photoreceptors in their eyes underlying color vision behavior. However, the
selective pressures giving rise to new photoreceptors and their spectral tuning
remain mostly obscure. Previously, we identified a violet receptor (UV2) that is
the result of a UV opsin gene duplication specific to Heliconius butterflies. At
the same time the violet receptor evolved, Heliconius evolved UV-yellow
coloration on their wings, due to the pigment 3-hydroxykynurenine (3-OHK) and the
nanostructure architecture of the scale cells. In order to better understand the
selective pressures giving rise to the violet receptor, we characterized opsin
expression patterns using immunostaining (14 species) and RNA-Seq (18 species),
and reconstructed evolutionary histories of visual traits in five major lineages
within Heliconius and one species from the genus Eueides. Opsin expression
patterns are hyperdiverse within Heliconius. We identified six unique retinal
mosaics and three distinct forms of sexual dimorphism based on ommatidial types
within the genus Heliconius. Additionally, phylogenetic analysis revealed
independent losses of opsin expression, pseudogenization events, and relaxation
of selection on UVRh2 in one lineage. Despite this diversity, the newly evolved
violet receptor is retained across most species and sexes surveyed.
Discriminability modeling of behaviorally preferred 3-OHK yellow wing coloration
suggests that the violet receptor may facilitate Heliconius color vision in the
context of conspecific recognition. Our observations give insights into the
selective pressures underlying the origins of new visual receptors.
PMID- 28505306
TI - Secretion of 2,3-dihydroxyisovalerate as a limiting factor for isobutanol
production in Saccharomyces cerevisiae.
AB - Isobutanol is a superior biofuel compared to ethanol, and it is naturally
produced by yeasts. Previously, Saccharomyces cerevisiae has been genetically
engineered to improve isobutanol production. We found that yeast cells engineered
for a cytosolic isobutanol biosynthesis secrete large amounts of the intermediate
2,3-dihydroxyisovalerate (DIV). This indicates that the enzyme dihydroxyacid
dehydratase (Ilv3) is limiting the isobutanol pathway and/or yeast exhibit
effective transport systems for the secretion of the intermediate, competing with
isobutanol synthesis. Moreover, we found that DIV cannot be taken up by the cells
again. To identify the responsible transporters, microarray analysis was
performed with a DIV producing strain compared to a wild type. Altogether, 19
genes encoding putative transporters were upregulated under DIV-producing
conditions. Thirteen of these were deleted together with five homologous genes. A
yro2 mrh1 deletion strain showed reduced DIV secretion, while a hxt5 deletion
mutant showed increased isobutanol production. However, a strain deleted for all
the 18 genes secreted even slightly increased amounts of the intermediates and
less isobutanol. The lactate transporter Jen1 turned out to transport the
intermediate 2-ketoisovalerate, but not DIV. The results suggest that the
transport of DIV is a rather complex process and several unspecific transporters
seem to be involved.
PMID- 28505308
TI - Diagnostic Performance of Ultrasound-Guided Fine-Needle Aspiration of Nonpalpable
Breast Lesions in a Multidisciplinary Setting: The Institut Curie's Experience.
AB - Objectives: To assess the diagnostic performance of ultrasound-guided fine-needle
aspiration (USFNA) in nonpalpable breast lesions (NPBLs) in a multidisciplinary
setting. Methods: In total, 2,601 NPBLs underwent USFNA by a radiologist
pathologist team. Gold-standard diagnosis was based on surgery, core-needle
biopsy, or 1-year imaging follow-up. USFNA's diagnostic performance was analyzed
in different clinical and imaging subgroups. Results: USFNA's sensitivity,
specificity, positive predictive value (PPV), and negative predictive value (NPV)
were, respectively, 92.6% (95% confidence interval [CI], 90.8%-94.2%), 96.8% (95%
CI, 95.8%-97.6%), 94.8% (95% CI, 93.2%-96.1%), and 95.4% (95% CI, 94.3%-96.4%).
The best PPV was achieved in Breast-Imaging Reporting and Data System (BI-RADS)
categories 4C and 5 and the best NPV in BI-RADS categories 2, 3, and 4A and in
patients younger than 50 years. The mitotic count, BI-RADS categories, associated
palpable cancer, and age (<50 or >=50 years) were statistically independent
factors ( P < .05) between USFNA's false-negative and true-positive results.
Conclusions: USFNA is a robust diagnostic procedure in NPBLs. Age and the BI-RADS
category of the lesion are important factors determining its performance.
PMID- 28505310
TI - Fact Finders-Clinical Perspectives.
PMID- 28505311
TI - Aspirin wears smart.
PMID- 28505309
TI - The herpes viral transcription factor ICP4 forms a novel DNA recognition complex.
AB - The transcription factor ICP4 from herpes simplex virus has a central role in
regulating the gene expression cascade which controls viral infection. Here we
present the crystal structure of the functionally essential ICP4 DNA binding
domain in complex with a segment from its own promoter, revealing a novel homo
dimeric fold. We also studied the complex in solution by small angle X-Ray
scattering, nuclear magnetic resonance and surface-plasmon resonance which
indicated that, in addition to the globular domain, a flanking intrinsically
disordered region also recognizes DNA. Together the data provides a rationale for
the bi-partite nature of the ICP4 DNA recognition consensus sequence as the
globular and disordered regions bind synergistically to adjacent DNA motifs.
Therefore in common with its eukaryotic host, the viral transcription factor ICP4
utilizes disordered regions to enhance the affinity and tune the specificity of
DNA interactions in tandem with a globular domain.
PMID- 28505312
TI - SODA: prediction of protein solubility from disorder and aggregation propensity.
AB - Solubility is an important, albeit not well understood, feature determining
protein behavior. It is of paramount importance in protein engineering, where
similar folded proteins may behave in very different ways in solution. Here we
present SODA, a novel method to predict the changes of protein solubility based
on several physico-chemical properties of the protein. SODA uses the propensity
of the protein sequence to aggregate as well as intrinsic disorder, plus
hydrophobicity and secondary structure preferences to estimate changes in
solubility. It has been trained and benchmarked on two different datasets. The
comparison to other recently published methods shows that SODA has state-of-the
art performance and is particularly well suited to predict mutations decreasing
solubility. The method is fast, returning results for single mutations in
seconds. A usage example estimating the full repertoire of mutations for a human
germline antibody highlights several solubility hotspots on the surface. The web
server, complete with RESTful interface and extensive help, can be accessed from
URL: http://protein.bio.unipd.it/soda.
PMID- 28505314
TI - Diversity of Mosquitoes (Diptera: Culicidae) Attracted to Human Subjects in
Rubber Plantations, Secondary Forests, and Villages in Luang Prabang Province,
Northern Lao PDR.
AB - The impact of the rapid expansion of rubber plantations in South-East Asia on
mosquito populations is uncertain. We compared the abundance and diversity of
adult mosquitoes using human-baited traps in four typical rural habitats in
northern Lao PDR: secondary forests, immature rubber plantations, mature rubber
plantations, and villages. Generalized estimating equations were used to explore
differences in mosquito abundance between habitats, and Simpson's diversity index
was used to measure species diversity. Over nine months, 24,927 female mosquitoes
were collected, including 51 species newly recorded in Lao PDR. A list of the 114
mosquito species identified is included. More mosquitoes, including vector
species, were collected in the secondary forest than immature rubber plantations
(rainy season, odds ratio [OR] 0.33, 95% confidence interval [CI] 0.31-0.36; dry
season, 0.46, 95% CI 0.41-0.51), mature rubber plantations (rainy season, OR
0.25, 95% CI 0.23-0.27; dry season, OR 0.25, 95% CI 0.22-0.28), and villages
(rainy season, OR 0.13, 95% CI 0.12-0.14; dry season, 0.20, 95% CI 0.18-0.23).
All habitats showed high species diversity (Simpson's indexes between 0.82-0.86)
with vectors of dengue, Japanese encephalitis (JE), lymphatic filariasis, and
malaria. In the secondary forests and rubber plantations, Aedes albopictus
(Skuse), a dengue vector, was the dominant mosquito species, while in the
villages, Culex vishnui (Theobald), a JE vector, was most common. This study has
increased the overall knowledge of mosquito fauna in Lao PDR. The high abundance
of Ae. albopictus in natural and man-made forests warrants concern, with vector
control measures currently only implemented in cities and villages.
PMID- 28505315
TI - Plasmid transfer efficiency using Lactoccocus lactis strains depends on
invasiveness status but also on plasmid copy number.
AB - Lactic acid bacteria as Lactococcus lactis are used as vector for protein but
also DNA delivery into intestinal cells in vitro and in vivo. For the plasmid
delivery strategy, the plasmid copy number per bacteria (PCN) is thus of great
importance. The aim of this paper is to determine the physiological conditions
when PCN is the highest in the bacteria. PCN was characterized by qPCR in five
different recombinant Lactococcus lactis strains, containing one (mono-) or two
different plasmids (biplasmidic), at exponential or stationary phase. We showed
that in all cases but one, PCN is higher at exponential than stationary phase.
PCN seems to depend on (i) monoplasmidic or biplasmidic strain; (ii) origin of
replication of the plasmid; and (iii) the DNA load of the bacteria. Then we
studied plasmid transfer in vitro from recombinant L. lactis to eukaryotic COS-7
cells using culture at exponential or stationary phase. We showed that plasmid
transfer can be improved in vitro by using bacteria at exponential phase.
PMID- 28505313
TI - Structural study of the Fox-1 RRM protein hydration reveals a role for key water
molecules in RRM-RNA recognition.
AB - The Fox-1 RNA recognition motif (RRM) domain is an important member of the RRM
protein family. We report a 1.8 A X-ray structure of the free Fox-1 containing
six distinct monomers. We use this and the nuclear magnetic resonance (NMR)
structure of the Fox-1 protein/RNA complex for molecular dynamics (MD) analyses
of the structured hydration. The individual monomers of the X-ray structure show
diverse hydration patterns, however, MD excellently reproduces the most occupied
hydration sites. Simulations of the protein/RNA complex show hydration consistent
with the isolated protein complemented by hydration sites specific to the
protein/RNA interface. MD predicts intricate hydration sites with water-binding
times extending up to hundreds of nanoseconds. We characterize two of them using
NMR spectroscopy, RNA binding with switchSENSE and free-energy calculations of
mutant proteins. Both hydration sites are experimentally confirmed and their
abolishment reduces the binding free-energy. A quantitative agreement between
theory and experiment is achieved for the S155A substitution but not for the
S122A mutant. The S155 hydration site is evolutionarily conserved within the RRM
domains. In conclusion, MD is an effective tool for predicting and interpreting
the hydration patterns of protein/RNA complexes. Hydration is not easily
detectable in NMR experiments but can affect stability of protein/RNA complexes.
PMID- 28505316
TI - Pancreas Atrophy and Islet Amyloid Deposition in Patients With Elderly-Onset Type
2 Diabetes.
AB - Context: With prolonged life expectancy, we often encounter patients with elderly
onset type 2 diabetes mellitus (eT2DM). Although the clinical features of eT2DM
are suggested to be different from those in patients with middle-age-onset type 2
diabetes mellitus (mT2DM), the islet pathologic features in eT2DM have not been
addressed. Objective: We attempted to characterize the pancreatic pathology in
eT2DM and sought its clinical implications. Materials and Methods: Pancreata from
13 young nondiabetic (age, 20 to 29 years), 27 patients with mT2DM (age, 45 to 87
years), 22 middle-age subjects without T2DM, 15 subjects with eT2DM (age, 85 to
100 years), and 30 elderly subjects without T2DM were investigated. Together with
conventional microscopic observations, morphometric analysis on the islet, islet
endocrine cells, and amyloid deposition was conducted on immunostained sections.
Results: The estimated age of diabetes onset was 80.8 +/- 1.4 years (mean +/-
standard error) in the eT2DM group and that of the mT2DM group was 48.3 +/- 2.4
years. The pancreatic weight was nearly 50% less in the eT2DM group than in the
other groups, showing duct obstruction with epithelial hyperplasia, marked acinar
atrophy, fibrosis, and amyloid deposition in the islet. The islet mass was
significantly reduced in the eT2DM group. The amyloid volume density correlated
inversely with the beta-cell volume density but not with the body mass index in
the eT2DM group. Laboratory data showed mild elevation of serum amylase in the
eT2DM group, although clinical signs and symptoms of pancreatitis were not
apparent. Conclusions: eT2DM is distinct from mT2DM and characterized by pancreas
atrophy, ductal lesions, and amyloid deposition.
PMID- 28505317
TI - Comparative assessment of conventional and light-curable fluoride varnish in the
prevention of enamel demineralization during fixed appliance therapy: a split
mouth randomized controlled trial.
AB - Objective: To evaluate the effects of single application of a conventional versus
light-curable fluoride varnish (LCFV) on prevention of enamel demineralization
during fixed orthodontic treatment over a 4 month period. Design: The research
was designed as a split-mouth, randomized control trial (RCT). Methods: Twenty
two patients requiring fixed orthodontic treatment with premolar extractions were
included in the RCT. In each patient, two diagonal quadrants (i.e. upper right
and lower left, or vice versa) were randomly assigned to receive conventional
fluoride varnish or LCFV. After allocation of one intervention, the other
diagonal quadrants received the second intervention. At specific time intervals,
premolars were extracted and sectioned, and the demineralized lesion was assessed
in each group. Main outcome measures: The primary outcome was demineralized
enamel lesion depth (DELD) at the end of 45, 90, and 120 days. Randomization: A
simple complete randomization list using random allocation rule (restricted
randomization) was computer generated to ensure homogeneity of application of
conventional or LCFV to each contralateral quadrant in a split-mouth design.
Allocation concealment was not employed. Blinding: Blinding was done only for
outcome assessor because of clinical limitations. Results: Twenty-two patients
with 88 teeth were enrolled in the trial. After excluding the drop-outs, primary
analysis was performed on 66 teeth distributed among two interventional groups.
Mean difference between DELD among two groups was 36.6 um [95 per cent confidence
interval (CI) 34.61-38.55] and 58.5 um [95 per cent confidence interval (CI)
55.65-61.43] at 90 and 120 days, respectively. Cluster level analysis performed
by Paired t-test showed that DELD was significantly higher (P < 0.001) in the
conventional fluoride varnish group at the end of 90 and 120 days as compared to
LCFV group. No adverse effect was observed in any patient. Limitations: Being a
histologic study, the role of fluoride varnish could be assessed only for 4
months. Conclusion: The result of this study indicate that single application of
LCFV (ClinproTM XT) can prevent enamel demineralization for longer duration (for
up to 4 months) of time as compared to conventional fluoride varnish (DuraphatTM,
45 days) during fixed appliance therapy. Registration: The trial was registered
retrospectively in the Clinical Trial Registry-India, number CTRI/2016/09/007232.
PMID- 28505318
TI - Calcified cerebral embolism: what the clinician needs to know.
PMID- 28505319
TI - Spinal cord ischaemia after endovascular aneurysm repair.
AB - We report the case of a patient who developed paraparesis 2 days after
endovascular aneurysm repair for a right common iliac aneurysm. The patient had
undergone thoracic endovascular aortic repair. The left subclavian artery was
occluded, but the left internal iliac artery was preserved. The patient fully
recovered from the paralysis within 3 months. This case illustrates the
importance of collateral blood supply to the spinal cord from the lumbosacral
region, especially when other sources are occluded.
PMID- 28505320
TI - Graph-based semi-supervised learning with genomic data integration using
condition-responsive genes applied to phenotype classification.
AB - Objective: Data integration methods that combine data from different molecular
levels such as genome, epigenome, transcriptome, etc., have received a great deal
of interest in the past few years. It has been demonstrated that the synergistic
effects of different biological data types can boost learning capabilities and
lead to a better understanding of the underlying interactions among molecular
levels. Methods: In this paper we present a graph-based semi-supervised
classification algorithm that incorporates latent biological knowledge in the
form of biological pathways with gene expression and DNA methylation data. The
process of graph construction from biological pathways is based on detecting
condition-responsive genes, where 3 sets of genes are finally extracted: all
condition responsive genes, high-frequency condition-responsive genes, and P
value-filtered genes. Results: The proposed approach is applied to ovarian cancer
data downloaded from the Human Genome Atlas. Extensive numerical experiments
demonstrate superior performance of the proposed approach compared to other state
of-the-art algorithms, including the latest graph-based classification
techniques. Conclusions: Simulation results demonstrate that integrating various
data types enhances classification performance and leads to a better
understanding of interrelations between diverse omics data types. The proposed
approach outperforms many of the state-of-the-art data integration algorithms.
PMID- 28505321
TI - Attention Problems as a Predictor of Type 1 Diabetes Adherence and Metabolic
Control Across Adolescence.
AB - Objective: Management of type 1 diabetes is a difficult self-regulatory process
requiring continued attention to complex regimen tasks. The purpose of this study
was to examine whether youths' attention problems were associated with poorer
adherence and HbA1c across time, and whether higher parental involvement reduced
these associations. Methods: Adolescents with type 1 diabetes (N = 199, M age =
12.43 years, SD = 1.50) and their mothers rated youths' attention problems and
adherence at three time points. Adolescents rated parents' diabetes-specific
monitoring and behavioral involvement. HbA1c was collected from medical records.
Results: Adolescents' (but not mothers') greater reports of attention problems
compared with their average related to lower adherence across time. Adolescents'
(but not mothers') reports of greater attention problems compared with their
average related to lower adherence across time. Conclusions: Youth attention
problems may help us understand poor adherence, and interventions to promote
parental involvement may buffer this risk.
PMID- 28505323
TI - The perception of spiritual health differences between citizens and physicians in
the Czech Republic.
AB - This paper focuses on a phenomenon known as spiritual health. Although the
scientific literature defines the concept of this health component (in relation
to other dimensions, i.e. physical, mental and social health), there is no
agreement concerning its relation to religiousness. The aim of this research is
to find out the views of citizens (n = 1810) and physicians (n = 1200) in the
Czech Republic on the potential dimension of health in its spiritual mode, and on
the understanding of its content by those who acknowledge its existence. One of
the main research findings is that physicians in the Czech Republic acknowledge
the existence of spiritual health (47.0%) to a significantly greater extent than
citizens of the country (26.4%). In both groups of respondents, the understanding
varies in the discourse of psychology (psychiatry), theology, in the preference
for harmony, and in medical care. The acknowledgement of spiritual health depends
strongly on gender (women acknowledge the existence of this phenomenon more than
men), religious belief (religious physicians, as well as religious citizens and
members and non-members of churches and religious societies, acknowledge the
existence of spiritual health significantly more compared with atheists) and
education (with increasing education the proportion of citizens who acknowledge
the existence of spiritual health rises considerably-the highest proportion is
found in university graduates). Spiritual health is shown to be an important
public health issue, even in a strongly secularized society.
PMID- 28505324
TI - Inequalities in smoking prevalence: a missed opportunity for tobacco control in
Pakistan.
AB - Background: Pakistan is one of the highest tobacco consuming countries in South
Asia and consumption is increasing. To implement equity orientated tobacco
control policies, the most vulnerable groups must be identified. We aimed to
identify these groups using the Pakistan Demographic and Health Survey (PDHS)
2012-13. Methods: Descriptive statistics, univariate and multivariate analyses
were used to explore household and participant characteristics associated with
smoking inside the home or tobacco smoking, respectively. Survey weights were
used to give nationally representative findings. Results: Data for 12 931
households, 3132 men and 13 538 women were examined. About 58.3% of surveyed
households were smoke-free, 39.1% were exposed to indoor tobacco smoke every day,
2.6% less frequently. Significantly more rural households were exposed to indoor
tobacco smoke than urban households (45.2% versus 34.9%). Of men, 28.3% reported
smoking compared with 1.3% of women. Smoking prevalence was higher in older age
groups. Increasing wealth was associated with lower smoking prevalence and indoor
smoking. For men, but not women, increasing education was associated with reduced
smoking. Conclusions: Inequalities in smoking behaviour impose harm to those who
can least afford the financial and health costs. Future tobacco control policies
in Pakistan must be sensitive to gender, geography and socio-economic status.
PMID- 28505325
TI - Expert Opinion #5.
PMID- 28505322
TI - Exosomes in Toxicology: Relevance to Chemical Exposure and Pathogenesis of
Environmentally Linked Diseases.
AB - Chronic exposure to environmental toxins has been known to initiate or aggravate
various neurological disorders, carcinomas and other adverse health effects.
Uptake by naive cells of pathogenic factors such as danger-associated molecules,
mRNAs, miRNAs or aggregated proteins leads to disruption in cellular homeostasis
further resulting in inflammation and disease propagation. Although early
research tended to focus solely on exosomal removal of unwanted cellular
contents, more recent reports indicate that these nano-vesicles play an active
role in intercellular signaling. Not only is the exosomal cargo cell type
specific, but it also differs between healthy and dying cells. Moreover,
following exosome uptake by naive cells, the contents from these vesicles can
alter the fate of recipient cells. Since exosomes can traverse long distances,
they can influence distantly located cells and tissues. This review briefly
explores the role played by environmental toxins in stimulating exosome release
in the context of progressive neurodegenerative diseases such as Alzheimer's,
Parkinson's, and Huntington's, as well as certain cancers such as lung, liver,
ovarian, and tracheal carcinomas.
PMID- 28505326
TI - Incidence of Bactericera cockerelli (Hemiptera: Triozidae) Under Different
Pesticide Regimes in the Lower Columbia Basin.
AB - Zebra chip is a potato disease transmitted by the potato psyllid Bactericera
cockerelli (Sulc) and distributed across several regions of the United States.
Because of its potentially devastating effects, the disease represents a threat
to the potato production and the industry particularly in the Pacific Northwest,
where it was first detected in 2011. Efforts to control the disease primarily
focus on managing the vector using pesticides. In this study, the effectiveness
of two pesticide spray programs in 2012 ("FULL" and "REDUCED") and three in 2013
("FULL 1," "FULL 2," and "REDUCED") against the potato psyllid was evaluated.
Yellow sticky cards were used to monitor the adults, whereas immatures were
evaluated by sampling the leaves. Overall, the vector infestation level in both
years was low. The mean total number of adults per trap in 2012 was 1.5, 5, and
12 for "FULL," "REDUCED," and the control, respectively, while in 2013 was 10.3,
20.7, 17.7, and 52 for "FULL 1," "FULL 2," "REDUCED," and the control,
respectively. For each particular year, season-long regimes were most effective
at controlling the pest than targeted applications; however, there was no
statistical difference among regimes ("FULL" or "REDUCED") after early July, when
the first psyllids were detected, until mid-August. Moreover, this number was
similar to the control. Also, psyllid density was uniform across sticky traps,
and no clear relationship was found between the proportion of Lso-infective
psyllids and zebra chip disease intensity.
PMID- 28505329
TI - ERRATUM.
PMID- 28505327
TI - Histone Deacetylase Inhibitor SAHA Is a Promising Treatment of Cushing Disease.
AB - Context: Remission failure following transsphenoidal surgery in Cushing disease
(CD) from pituitary corticotroph tumors (CtTs) remains clinically challenging.
Histone deacetylase inhibitors (HDACis) are antitumor drugs approved for clinical
use, with the potential to affect adrenocorticotropin hormone (ACTH)
hypersecretion by inhibiting pro-opiomelanocortin (POMC) transcription.
Objective: Testing the efficacy of suberoylanilide hydroxamic acid (SAHA) on
human and murine ACTH-secreting tumor (AtT-20) cells. Design: Cell viability,
ACTH secretion (enzyme-linked immunosorbent assay), apoptosis, and gene
expression profile were investigated on AtT-20 cells. In vivo efficacy was
examined in an athymic nude mouse AtT-20 xenograft model. SAHA efficacy against
human-derived corticotroph tumor (hCtT) (n = 8) was tested in vitro. Setting:
National Institutes of Health. Intervention: SAHA (0.5 to 8 uM). Main Outcome
Measures: AtT-20 and hCtT cell survival, in vitro/invivo ACTH measurements.
Results: SAHA (1 uM) reduced AtT-20 viability to 75% at 24 hours, 43% at 48 hours
(analysis of variance; P = 0.002). Apoptosis was confirmed with elevated BAX/Bcl2
ratio and FACS. Intriguingly, early (3-hour) significant decline (70%; P <
0.0001) of secreted ACTH and diminished POMC transcription was observed with SAHA
(1 uM). Microarray analysis revealed a direct association between liver X
receptor alpha (LXRalpha) and POMC expression. Accordingly, SAHA reduced LXRalpha
in AtT-20 cells but not in normal murine corticotrophs. Xenografted nude-mice
tumor involution (126 +/- 33/160 +/- 35 vs 337 +/- 49 mm3; P = 0.0005) was
observed with 5-day intraperitoneal SAHA, with reversal of elevated ACTH (P <
0.0001). SAHA did not affect serum ACTH in nontumor mice. Lastly, we confirmed
that SAHA (1 uM/24 h) decreased hCtT survival (78.92%; P = 0.0007) and ACTH
secretion (83.64%; P = 0.03). Conclusion: Our findings demonstrate SAHA's
efficacy in reducing survival and ACTH secretion in AtT-20 and hCtT cells,
providing a potential intervention for recurrent/unremitting CD.
PMID- 28505330
TI - Acinetobacter baumannii transfers the blaNDM-1 gene via outer membrane vesicles.
AB - Objectives: To investigate the transmission of the gene encoding New Delhi
metallo-beta-lactamase-1 ( bla NDM-1 ) through outer membrane vesicles (OMVs)
released from an Acinetobacter baumannii strain (A_115). Methods: Isolation and
purification of OMVs by density gradient from a carbapenem-resistant clinical
strain of A. baumannii harbouring plasmid-mediated bla NDM-1 and aac(6')-Ib-cr
genes was performed. DNA was purified from the OMVs and used for PCR and dot-blot
analysis. Vesicles treated with DNase I and proteinase K were used to transform
A. baumannii ATCC 19606 and Escherichia coli JM109 strains. MIC values for the
transformants were determined, followed by PCR and restriction digestion of
plasmids. PFGE was done for A_115 and transformants of ATCC 19606 and JM109.
Results: The A. baumannii strain (ST 1462) released vesicles (25-100 nm) during
in vitro growth at late log phase. PCR and dot-blot analysis confirmed the
presence of bla NDM-1 and aac(6')-Ib-cr genes in intravesicular DNA. bla NDM-1
and aac(6')-Ib-cr genes were transferred to both the A. baumannii ATCC 19606 and
E. coli JM109 recipient cells. The transformation frequency of the purified OMVs
was in the range of 10 -5 -10 -6 and gradually reduced with storage of OMVs. The
sizes of the plasmids in the transformants and their restriction digestion
patterns were identical to the plasmid in A_115. The transformants showed
elevated MIC values of the beta-lactam group of antibiotics, which confirmed the
presence of a bla NDM-1 -harbouring plasmid. Conclusions: This is the first
experimental evidence of intra- and inter-species transfer of a plasmid
harbouring a bla NDM-1 gene in A. baumannii via OMVs with high transformation
frequency.
PMID- 28505328
TI - Advanced Human Immunodeficiency Virus Disease in Botswana Following Successful
Antiretroviral Therapy Rollout: Incidence of and Temporal Trends in Cryptococcal
Meningitis.
AB - Background: Botswana has a well-developed antiretroviral therapy (ART) program
that serves as a regional model. With wide ART availability, the burden of
advanced human immunodeficiency virus (HIV) and associated opportunistic
infections would be expected to decline. We performed a nationwide surveillance
study to determine the national incidence of cryptococcal meningitis (CM), and
describe characteristics of cases during 2000-2014 and temporal trends at 2
national referral hospitals. Methods: Cerebrospinal fluid data from all 37
laboratories performing meningitis diagnostics in Botswana were collected from
the period 2000-2014 to identify cases of CM. Basic demographic and laboratory
data were recorded. Complete national data from 2013-2014 were used to calculate
national incidence using UNAIDS population estimates. Temporal trends in cases
were derived from national referral centers in the period 2004-2014. Results: A
total of 5296 episodes of CM were observed in 4702 individuals; 60.6% were male,
and median age was 36 years. Overall 2013-2014 incidence was 17.8 (95% confidence
interval [CI], 16.6-19.2) cases per 100000 person-years. In the HIV-infected
population, incidence was 96.8 (95% CI, 90.0-104.0) cases per 100000 person
years; male predominance was seen across CD4 strata. At national referral
hospitals, cases decreased during 2007-2009 but stabilized during 2010-2014.
Conclusions: Despite excellent ART coverage in Botswana, there is still a
substantial burden of advanced HIV, with 2013-2014 incidence of CM comparable to
pre-ART era rates in South Africa. Our findings suggest that a key population of
individuals, often men, is developing advanced disease and associated
opportunistic infections due to a failure to effectively engage in care,
highlighting the need for differentiated care models.
PMID- 28505331
TI - Antimicrobial susceptibility of clinical isolates of Neisseria gonorrhoeae to
alternative antimicrobials with therapeutic potential.
AB - Background: The prevalence of MDR Neisseria gonorrhoeae is increasing globally
and represents a public health emergency. Development and approval of new anti
gonococcal agents may take years. As a concurrent approach to developing new
antimicrobials, the laboratory and clinical evaluation of currently licensed
antimicrobials not widely used for the treatment of gonorrhoea may provide new
options for the treatment of gonococcal infections. Objectives: To determine the
in vitro activity of nine alternative, currently licensed and late-development
antimicrobials with the potential to treat gonococcal infections against 112
clinical isolates of N. gonorrhoeae resistant to one or multiple antimicrobials.
Methods: The MICs of conventional anti-gonococcal antimicrobials (penicillin,
ceftriaxone, cefixime, azithromycin, ciprofloxacin, tetracycline and
spectinomycin) and alternative antimicrobials (ertapenem, gentamicin, netilmicin,
tigecycline, eravacycline, fosfomycin, linezolid, ceftazidime/avibactam and
ceftaroline) were determined by agar dilution. Results: Ertapenem and the novel
cephalosporins demonstrated similar MIC values to the third-generation
cephalosporins, but increased MICs were observed for isolates with increased
cefixime and ceftriaxone MICs. Tigecycline and eravacycline had MIC values below
expected serum concentrations for all isolates tested. The aminoglycosides
gentamicin and netilmicin were generally more potent than spectinomycin, with
netilmicin demonstrating the greatest potency. Fosfomycin MICs were elevated
compared with other agents, but remained within the MIC range for susceptible
organisms, while linezolid MICs were generally higher than those for organisms
considered resistant. Conclusions: Among potentially therapeutically useful
alternative agents, the aminoglycosides, eravacycline, tigecycline and fosfomycin
had good in vitro activity. The novel cephalosporins and ertapenem had comparable
activity to cefixime and ceftriaxone.
PMID- 28505332
TI - A Comparative Benchmark Dose Study for N, N-Dimethylformamide Induced Liver
Injury in a Chinese Occupational Cohort.
AB - Widespread contamination of N,N-dimethylformamide (DMF) has been identified in
the environment of leather industries and their surrounding residential areas.
Few studies have assessed the dose-response relationships between internal
exposure biomarkers and liver injury in DMF exposed populations. We assessed
urinary N-methylformamide (NMF) and N-acetyl-S-(N-methylcarbamoyl) cysteine
(AMCC) and blood N-methylcarbmoylated hemoglobin (NMHb) levels in 698 Chinese DMF
exposed workers and 188 nonDMF- exposed workers using ultraperformance liquid
chromatography tandem mass-spectrometry. Liver injury was defined as having
abnormal serum activities of any of the 3 liver enzymes, including alanine
aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase.
Higher liver injury rates were identified in DMF-exposed workers versus nonDMF
exposed workers (9.17% vs 4.26%, P = .029) and in male versus female workers
(11.4% vs 3.2%, P < .001). Positive correlations between environmental exposure
categories and internal biomarker levels were identified with all 3 biomarkers
undetectable in nonDMF-exposed workers. Lower confidence limit of benchmark dose
(BMDL) was estimated using the benchmark dose (BMD) method. Within all study
subjects, BMDLs of 14.0 mg/l for NMF, 155 mg/l for AMCC, and 93.3 nmol/g for NMHb
were estimated based on dose-response relationships between internal levels and
liver injury rates. Among male workers, BMDLs of 10.9 mg/l for NMF, 119 mg/l for
AMCC, and 97.0 nmol/g for NMHb were estimated. In conclusion, NMF, AMCC, and NMHb
are specific and reliable biomarkers and correlate well with DMF-induced
hepatotoxicity. NMF correlates the best with liver injury, while NMHb may be the
most stable indicator. Males have a greater risk of liver injury than females
upon DMF exposure.
PMID- 28505334
TI - DIRECTION: a machine learning framework for predicting and characterizing DNA
methylation and hydroxymethylation in mammalian genomes.
AB - Motivation: 5-Methylcytosine and 5-Hydroxymethylcytosine in DNA are major
epigenetic modifications known to significantly alter mammalian gene expression.
High-throughput assays to detect these modifications are expensive, labor
intensive, unfeasible in some contexts and leave a portion of the genome
unqueried. Hence, we devised a novel, supervised, integrative learning framework
to perform whole-genome methylation and hydroxymethylation predictions in CpG
dinucleotides. Our framework can also perform imputation of missing or low
quality data in existing sequencing datasets. Additionally, we developed
infrastructure to perform in silico, high-throughput hypotheses testing on such
predicted methylation or hydroxymethylation maps. Results: We test our approach
on H1 human embryonic stem cells and H1-derived neural progenitor cells. Our
predictive model is comparable in accuracy to other state-of-the-art DNA
methylation prediction algorithms. We are the first to predict hydroxymethylation
in silico with high whole-genome accuracy, paving the way for large-scale
reconstruction of hydroxymethylation maps in mammalian model systems. We designed
a novel, beam-search driven feature selection algorithm to identify the most
discriminative predictor variables, and developed a platform for performing
integrative analysis and reconstruction of the epigenome. Our toolkit DIRECTION
provides predictions at single nucleotide resolution and identifies relevant
features based on resource availability. This offers enhanced biological
interpretability of results potentially leading to a better understanding of
epigenetic gene regulation. Availability and implementation:
http://www.pradiptaray.com/direction, under CC-by-SA license. Contacts:
pradiptaray@gmail.com or mchen@utdallas.edu or michael.zhang@utdallas.edu.
Supplementary information: Supplementary data are available at Bioinformatics
online.
PMID- 28505335
TI - Functional analysis of novel RUNX2 mutations in cleidocranial dysplasia.
AB - Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal disorder
caused by mutation of runt-related transcription factor 2 (RUNX2) gene. The
purpose of this study was to explore novel RUNX2 mutations in seven individuals
with CCD and investigate the function of the mutant RUNX2 proteins. DNA samples
were prepared from the peripheral blood of the CCD individuals, and then
subjected to DNA sequencing. Conservation and secondary structure analysis were
performed based on RUNX2 sequencing results. pEGFP-C1 plasmids containing GFP
tagged wild-type RUNX2 and three novel RUNX2 mutations expression cassettes were
constructed, and then transfected into HEK293T cells. Cell fluorescence,
luciferase assay and western blotting were used to analyse the subcellular
distribution and function of the mutant RUNX2 proteins. Three novel mutations
(R193G, 258fs, Y400X) were found in the seven CCD patients. Conservation and
structure analysis show one novel mutation (R193G) in Runt domain and two novel
mutations (258fs and Y400X) in PST domain of RUNX2. Western blotting confirmed
that the 258fs and Y400X mutations produced truncated proteins. Fluorescence
detection showed that the three novel mutants localised exclusively in the
nucleus. However, luciferase assay indicated all mutants severely impaired the
transactivation activities of RUNX2 on osteocalcin promoter. Our results broaden
the spectrum of RUNX2 mutations in CCD individuals and demonstrated that loss of
function in RUNX2 is responsible for CCD.
PMID- 28505336
TI - Financial Capacity and its Cognitive Predictors in Progressive Multiple
Sclerosis.
AB - Objective: Financial capacity is a cognitively-complex activity of daily living
that has been shown to decline in a number of neurocognitive disorders. Although
it has been well established that cognitive decline is common in multiple
sclerosis (MS), little is known about possible financial capacity impairment in
people with MS. Thus, the objective of the current study is to investigate
financial capacity and its neurocognitive correlates in MS. Methods: Data from 22
people with progressive MS and a healthy comparison group composed of 18 adults
were analyzed. MS diagnoses were made by a board-certified neurologist with
experience in MS. Study participants were administered the Financial Capacity
Instrument, a performance-based measure of financial capacity, and
neuropsychological battery. Results: Overall financial capacity and most complex
financial domains were significantly poorer for people with progressive MS in
relation to the healthy comparison group, and a number of cognitive variables
were associated with financial capacity declines. Conclusions: Financial capacity
is a complex cognitively-mediated functional ability that was impaired in 50% of
the current sample of people with progressive MS. These results indicate that
people with progressive MS are at greater risk for showing impairment in complex
financial tasks and should be clinically monitored for possible deficits in
financial capacity.
PMID- 28505333
TI - Multiregional Age-Associated Reduction of Brain Neuronal Reserve Without
Association With Neurofibrillary Degeneration or beta-Amyloidosis.
AB - Increase in human life expectancy has resulted in the rapid growth of the elderly
population with minimal or no intellectual deterioration. The aim of this
stereological study of 10 structures and 5 subdivisions with and without
neurofibrillary degeneration in the brains of 28 individuals 25-102-years-old was
to establish the pattern of age-associated neurodegeneration and neuronal loss in
the brains of nondemented adults and elderly. The study revealed the absence of
significant neuronal loss in 7 regions and topographically selective reduction of
neuronal reserve over 77 years in 8 brain structures including the entorhinal
cortex (EC) (-33.3%), the second layer of the EC (-54%), cornu Ammonis sector 1
(CA1) (-28.5%), amygdala, (-45.8%), thalamus (-40.5%), caudate nucleus (-35%),
Purkinje cells (-48.3%), and neurons in the dentate nucleus (40.1%). A similar
rate of neuronal loss in adults and elderly, without signs of accelerating
neuronal loss in agers or super-agers, appears to indicate age-associated brain
remodeling with significant reduction of neuronal reserve in 8 brain regions.
Multivariate analysis demonstrates the absence of a significant association
between neuronal loss and the severity of neurofibrillary degeneration and beta
amyloidosis, and a similar rate of age-associated neuronal loss in structures
with and without neurofibrillary degeneration.
PMID- 28505337
TI - Sex Differences in Brain Regions Modulating Pain Among Older Adults: A Cross
Sectional Resting State Functional Connectivity Study.
AB - Objective: A long-standing hypothesis is that when compared with males, females
may be at increased risk of experiencing greater pain sensitivity and
unpleasantness. The purpose of this study was to examine sex differences in pain
psychophysics and resting state functional connectivity (RSFC) in core pain
regions in an age- and sex-matched sample of healthy older adults. Design:
Between groups, cross-sectional. Setting: Vanderbilt University and Medical
Center. Subjects: The sample in the analyses reported here consisted of 19
cognitively intact males matched with 19 cognitively intact females of similar
ages (median ages: females = 70 years, males = 68 years). Methods: Psychophysical
assessment of experimental thermal pain and RSFC. Results: There were no
significant differences in perceptual thresholds or unpleasantness ratings in
response to thermal stimuli. Older males showed greater RSFC between the
affective and sensory networks and between affective and descending modulatory
networks. Conversely, older females showed greater RSFC between the descending
modulatory network and both sensory and affective networks. The strongest
evidence for sex differences emerged in the associations of thermal pain with
RSFC between the anterior cingulate cortex (ACC) and amygdala and between the ACC
and periaqueductal gray matter in older females relative to older males.
Conclusions: We found no differences in pain sensitivity or pain affect between
older males and older females. Additionally, we found that older females
exhibited a greater association between thermal pain sensitivity and RSFC signal
between regions typically associated with pain affect and the descending
modulatory system. One interpretation of these findings is that older females may
better engage the descending pain modulatory system. This better engagement
possibly translates into older females having similar perceptual thresholds for
temperature sensitivity and unpleasantness associated with mild and moderate
pain. These findings contrast with studies demonstrating that younger females
find thermal pain more sensitive and more unpleasant.
PMID- 28505338
TI - Concordance Between Anal and Oral Human Papillomavirus Infections Among Young Men
Who have Sex With Men.
AB - Prevalence of human papillomavirus (HPV) infections was assessed among 1033 young
men who have sex with men (MSM) aged 18-26 years. HPV (any type) was detected in
742 (71.8%) anal specimens and 101 (9.8%) oral specimens. Although HPV was
detected in specimens from both anatomical sites in 83 (8.0%) participants, type
specific concordance for at least 1 HPV type was found in only 35 (3.4%)
participants. HIV and smoking were associated with higher prevalence at both
sites and frequency of concordant types. Coinfections of identical HPV types were
rare, suggesting independent infection events and/or different modes of
clearance.
PMID- 28505339
TI - LabRS: A Rosetta stone for retrospective standardization of clinical laboratory
test results.
AB - Objective: Clinical laboratories in the United States do not have an explicit
result standard to report the 7 billion laboratory tests results they produce
each year. The absence of standardized test results creates inefficiencies and
ambiguities for secondary data users. We developed and tested a tool to
standardize the results of laboratory tests in a large, multicenter clinical data
warehouse. Methods: Laboratory records, each of which consisted of a laboratory
result and a test identifier, from 27 diverse facilities were captured from 2000
through 2015. Each record underwent a standardization process to convert the
original result into a format amenable to secondary data analysis. The
standardization process included the correction of typos, normalization of
categorical results, separation of inequalities from numbers, and conversion of
numbers represented by words (eg, "million") to numerals. Quality control
included expert review. Results: We obtained 1.266 * 109 laboratory records and
standardized 1.252 * 109 records (98.9%). Of the unique unstandardized records
(78.887 * 103), most appeared <5 times (96%, eg, typos), did not have a test
identifier (47%), or belonged to an esoteric test with <100 results (2%).
Overall, these 3 reasons accounted for nearly all unstandardized results (98%).
Conclusion: Current results suggest that the tool is both scalable and
generalizable among diverse clinical laboratories. Based on observed trends, the
tool will require ongoing maintenance to stay current with new tests and result
formats. Future work to develop and implement an explicit standard for test
results would reduce the need to retrospectively standardize test results.
PMID- 28505340
TI - Members of Microvirga and Bradyrhizobium genera are native endosymbiotic bacteria
nodulating Lupinus luteus in Northern Tunisian soils.
AB - The genetic diversity of bacterial populations nodulating Lupinus luteus (yellow
lupine) in Northern Tunisia was examined. Phylogenetic analyses of 43 isolates
based on recA and gyrB partial sequences grouped them in three clusters, two of
which belong to genus Bradyrhizobium (41 isolates) and one, remarkably, to
Microvirga (2 isolates), a genus never previously described as microsymbiont of
this lupine species. Representatives of the three clusters were analysed in-depth
by multilocus sequence analysis of five housekeeping genes (rrs, recA, glnII,
gyrB and dnaK). Surprisingly, the Bradyrhizobium cluster with the two isolates
LluI4 and LluTb2 may constitute a new species defined by a separate position
between Bradyrhizobium manausense and B. denitrificans. A nodC-based phylogeny
identified only two groups: one formed by Bradyrhizobium strains included in the
symbiovar genistearum and the other by the Microvirga strains. Symbiotic
behaviour of representative isolates was tested, and among the seven legumes
inoculated only a difference was observed i.e. the Bradyrhizobium strains
nodulated Ornithopus compressus unlike the two strains of Microvirga. On the
basis of these data, we conclude that L. luteus root nodule symbionts in Northern
Tunisia are mostly strains within the B. canariense/B. lupini lineages, and the
remaining strains belong to two groups not previously identified as L. luteus
endosymbionts: one corresponding to a new clade of Bradyrhizobium and the other
to the genus Microvirga.
PMID- 28505342
TI - Letter to the Editor: Author Response - Analysis of Rhizome Development in Oryza
longistaminata, a Wild Rice Species.
PMID- 28505341
TI - Association of Changes in Neighborhood-Level Racial Residential Segregation With
Changes in Blood Pressure Among Black Adults: The CARDIA Study.
AB - Importance: Despite cross-sectional evidence linking racial residential
segregation to hypertension prevalence among non-Hispanic blacks, it remains
unclear how changes in exposure to neighborhood segregation may be associated
with changes in blood pressure. Objective: To examine the association of changes
in neighborhood-level racial residential segregation with changes in systolic and
diastolic blood pressure over a 25-year period. Design, Setting, and
Participants: This observational study examined longitudinal data of 2280 black
participants of the Coronary Artery Risk Development in Young Adults (CARDIA)
study, a prospective investigation of adults aged 18 to 30 years who underwent
baseline examinations in field centers in 4 US locations from March 25, 1985, to
June 7, 1986, and then were re-examined for the next 25 years. Racial residential
segregation was assessed using the Getis-Ord Gi* statistic, a measure of SD
between the neighborhood's racial composition (ie, percentage of black residents)
and the surrounding area's racial composition. Segregation was categorized as
high (Gi* >1.96), medium (Gi* 0-1.96), and low (Gi* <0). Fixed-effects linear
regression modeling was used to estimate the associations of within-person change
in exposure to segregation and within-person change in blood pressure while
tightly controlling for time-invariant confounders. Data analyses were performed
between August 4, 2016, and February 9, 2017. Main Outcomes and Measures: Within
person changes in systolic and diastolic blood pressure across 6 examinations
over 25 years. Results: Of the 2280 participants at baseline, 974 (42.7%) were
men and 1306 (57.3%) were women. Of these, 1861 (81.6%) were living in a high
segregation neighborhood; 278 (12.2%), a medium-segregation neighborhood; and 141
(6.2%), a low-segregation neighborhood. Systolic blood pressure increased by a
mean of 0.16 (95% CI, 0.06-0.26) mm Hg with each 1-SD increase in segregation
score after adjusting for interactions of time with age, sex, and field center.
Of the 1861 participants (81.6%) who lived in high-segregation neighborhoods at
baseline, reductions in exposure to segregation were associated with reductions
in systolic blood pressure. Mean differences in systolic blood pressure were
1.33 (95% CI, -2.26 to -0.40) mm Hg when comparing high-segregation with medium
segregation neighborhoods and -1.19 (95% CI, -2.08 to -0.31) mm Hg when comparing
high-segregation with low-segregation neighborhoods after adjustment for time and
interactions of time with baseline age, sex, and field center. Changes in
segregation were not associated with changes in diastolic blood pressure.
Conclusions and Relevance: Decreases in exposure to racial residential
segregation are associated with reductions in systolic blood pressure. This study
adds to the small but growing body of evidence that policies that reduce
segregation may have meaningful health benefits.
PMID- 28505343
TI - Training issues in ultrasound and the benefits of an International Fellowship.
PMID- 28505345
TI - Cardio-oncology: a multidisciplinary approach for detection, prevention and
management of cardiac dysfunction in cancer patients.
AB - Cardiac dysfunction that develops during or after completion of cancer therapy is
a growing health concern that should be addressed in a multidisciplinary setting.
Cardio-oncology is a new discipline that focuses on screening, monitoring and
treating cardiovascular disease during and after cancer treatment. A baseline
cardiovascular risk assessment is essential. For high-risk patients, a tailored
and detailed plan for cardiovascular management throughout treatment and beyond
should also be established. Anthracycline and/or trastuzumab-containing
chemotherapy and chest-directed radiation therapy are well known cardiotoxic
cancer therapies. Monitoring for the development of subclinical cardiotoxicity is
crucial for the prevention of clinical heart failure. Detecting a decreased left
ventricular ejection fraction after cancer therapy might be a late finding;
therefore, earlier markers of cardiac injury are being actively explored.
Abnormal myocardial strain and increased serum cardiac biomarkers (e.g. troponins
and natriuretic peptides) are possible candidates for this purpose. An important
method for preventing heart failure is the avoidance or minimization of the use
of cardiotoxic therapies. Decisions must balance the anti-tumor efficacy of the
treatment with its potential cardiotoxicity. If patients develop cardiac
dysfunction or heart failure, they should be treated in accordance with
established guidelines for heart failure. Cancer survivors who have been exposed
to cardiotoxic cancer therapies are at high risk of developing heart failure. The
management of cardiovascular risk factors and periodic screening with cardiac
imaging and biomarkers should be considered in high-risk survivors.
PMID- 28505346
TI - Breast cancer screening (BCS) chart: a basic and preliminary model for making
screening mammography more productive and efficient.
AB - BACKGROUND: The breast cancer screening (BCS) chart is suggested as a basic and
preliminary tool to improve efficiency of screening mammography. METHODS: We
conducted this case-control study in 2016 and enrolled 1422 women aged 30-75
years, including 506 women with breast cancer (cases) and 916 women without
breast cancer (controls). We developed the BCS chart using a multiple logistic
regression analysis. We combined the risks of breast cancer to predict the
individual risk of breast cancer. Then, we stratified and colored the predicted
risk probabilities as follows: <05% (green), 05-09% (yellow), 10-14% (orange), 15
19% (red), 20-24% (brown) and >=25% (black). RESULTS: The BCS chart provides the
risk probability of breast cancer, based on age, body mass index, late menopause,
having a benign breast disease and a positive family history of breast cancer
among the first-degree or the second/third-degree relatives. According to this
chart, an individual can be classified in a category of low risk (green), medium
risk (yellow and orange), high risk (red and brown) and very high risk (black)
for breast cancer. CONCLUSIONS: This chart is a flexible and easy to use tool
that can detect high-risk subjects and make the screening program more efficient
and productive.
PMID- 28505347
TI - Body-weight and psychological well-being in the UK general population.
AB - Background: While the consequences of body weight for physical health are well
explored, the evidence for psychological well-being is less straightforward. An
instrumental variable approach is used to address the endogenous relationship
between body weight and well-being in the UK general population. Methods: Data
from the Health Survey for England (2003, 2004 and 2006) are used to fit linear
and ordered probit instrument variable models for a sample of 13 862 individuals,
with frequent white meat consumption instrumenting for body-weight. Non
linearities in the relationship, robustness to weak instruments and relaxation of
strict exogeneity assumption are further examined. Results: Accounting for
endogeneity and conditional on health a protective effect on well-being is
observed. A unit increase in body mass index (BMI) improves General Health
Questionnaire (GHQ) by 0.17 (95% CI: 0.02-0.31) points and reduces the
probability of reporting very low GHQ by 2.5% (95% CI: 0.01-0.05). Empirical
testing showed that the instrument performs well, with increased meat consumption
adding 0.58 points (95% CI: 0.42-0.74) to ones' BMI. Conclusions: We present
support for the jolly-fat hypothesis, however, caution is recommended in drawing
inferences. Further research needs to resolve the mixed findings in the
literature.
PMID- 28505344
TI - Genetics of glaucoma.
AB - Genetic and genomic studies, including genome-wide association studies (GWAS)
have accelerated the discovery of genes contributing to glaucoma, the leading
cause of irreversible blindness world-wide. Glaucoma can occur at all ages, with
Mendelian inheritance typical for the rare early onset disease (before age 40)
and complex inheritance evident in common adult-onset forms of disease. Recent
studies have suggested possible therapeutic targets for some patients with early
onset glaucoma based on the molecular and cellular events caused by MYOC, OPTN
and TBK1 mutations. Diagnostic genetic tests using early-onset glaucoma genes are
also proving useful for pre-symptomatic disease detection and genetic counseling.
Recent GWAS completed for three types of common adult-onset glaucoma have
identified novel loci for POAG (primary-open-angle glaucoma) (ABCA1, AFAP1, GMDS,
PMM2, TGFBR3, FNDC3B, ARHGEF12, GAS7, FOXC1, ATXN2, TXNRD2); PACG (primary angle
closure glaucoma (EPDR1, CHAT, GLIS3, FERMT2, DPM2-FAM102); and exfoliation
syndrome (XFS) glaucoma (CACNA1A). In total sixteen genomic regions have been
associated with POAG (including the normal tension glaucoma (NTG) subgroup), 8
with PACG and 2 with XFS. These studies are defining important biological
pathways and processes that contribute to disease pathogenesis.
PMID- 28505350
TI - Evidence of Altered Trigeminal Nociception in an Animal Model of Fibromyalgia.
AB - Objective: Fibromyalgia (FM) is a debilitating chronic condition that
significantly affects quality of life. A strong association has been demonstrated
between FM and chronic pain in the trigeminal region in clinical studies. This
study was performed to evaluate the response to acute and chronic noxious stimuli
applied to the facial region. Methods: Adult male Wistar rats (250-270 g, N = 10
for each group) were used in the current study. A subchronic swim stress model
was used as the animal model of FM. Anxiety-like behaviors and response to acute
and chronic noxious stimuli were assayed using the elevated plus maze, eye wiping
test, and orofacial formalin test, respectively. Balance and motor function were
evaluated using rotarod and wire grip tests. Results: An increased anxiety-like
behavior was observed in swim stress rats in comparison with control and sham
subjects. Response to acute and chronic noxious stimuli in the trigeminal region
was increased in the stressed rats. Motor and balance function were not altered
following stress. Conclusions: Results of the current study demonstrated a
hyperalgesic state in the trigeminal region in a possible animal model of FM.
This study provides a reliable animal model for further research on the possible
mechanisms of orofacial pain in FM.
PMID- 28505349
TI - Decline of Ecological Functions Performed by Dung Beetles in Areas of Atlantic
Forest and Contribution of Rollers and Tunnellers in Organic Matter Removal.
AB - The feeding behavior of the Scarabaeinae subfamily has positive implications on
ecosystem functioning. We characterize the necrophagous and coprophagous dung
beetle assemblages, and we quantify the removal of swine carrion and domestic dog
dung in two areas with different degrees of environmental disturbance in an
Atlantic Forest remnant located in Florianopolis, SC, Brazil. The experiment was
setup at eight sampling points in each area, by installing one control and two
collection and removal assessment arenas for collecting necrophagous dung beetles
while simultaneously evaluating the removal of carrion (50 g of rotting pork for
48 h). We used the same sample design with 50 g of domestic dog dung for
evaluating the coprophagous dung beetle assemblage and dung removal. Our results
indicated that necrophagous dung beetles were more sensitive to environmental
disturbance owing to a lower richness and changes in species dominance, which
resulted in a lower removal in the areas with greater disturbance and lower
environmental quality (39.6% carrion removal) in relation to less disturbed areas
(75.1% carrion removal). The dung beetle assemblages were similar in structure
and removal rates between areas (80% of dung was removed). In assessing the
influence of richness, abundance, and biomass of dung beetles on resource removal
both for the whole assemblage and for each separate functional guild, only the
abundance and biomass of rollers contributed significantly to dung removal. These
results highlight the implications of environmental disturbances on the functions
of dung beetles, which respond differently according to the resource they use.
PMID- 28505348
TI - Implication of the box C/D snoRNP assembly factor Rsa1p in U3 snoRNP assembly.
AB - The U3 box C/D snoRNA is one key element of 90S pre-ribosome. It contains a 5?
domain pairing with pre-rRNA and the U3B/C and U3C?/D motifs for U3 packaging
into a unique small nucleolar ribonucleoprotein particle (snoRNP). The RNA
binding protein Snu13/SNU13 nucleates on U3B/C the assembly of box C/D proteins
Nop1p/FBL and Nop56p/NOP56, and the U3-specific protein Rrp9p/U3-55K.
Snu13p/SNU13 has a much lower affinity for U3C?/D but nevertheless forms on this
motif an RNP with box C/D proteins Nop1p/FBL and Nop58p/NOP58. In this study, we
characterized the influence of the RNP assembly protein Rsa1 in the early steps
of U3 snoRNP biogenesis in yeast and we propose a refined model of U3 snoRNP
biogenesis. While recombinant Snu13p enhances the binding of Rrp9p to U3B/C, we
observed that Rsa1p has no effect on this activity but forms with Snu13p and
Rrp9p a U3B/C pre-RNP. In contrast, we found that Rsa1p enhances Snu13p binding
on U3C?/D. RNA footprinting experiments indicate that this positive effect most
likely occurs by direct contacts of Rsa1p with the U3 snoRNA 5? domain. In light
of the recent U3 snoRNP cryo-EM structures, our data suggest that Rsa1p has a
dual role by also preventing formation of a pre-mature functional U3 RNP.
PMID- 28505351
TI - Centre effects and peritoneal dialysis-related peritonitis.
PMID- 28505352
TI - The Nodulin 26-like intrinsic membrane protein OsNIP3;2 is involved in arsenite
uptake by lateral roots in rice.
AB - Previous studies have shown that the Nodulin 26-like intrinsic membrane protein
(NIP) Lsi1 (OsNIP2;1) is involved in arsenite [As(III)] uptake in rice (Oryza
sativa). However, the role of other rice NIPs in As(III) accumulation in planta
remains unknown. In the present study, we investigated the role OsNIP3;2 in
As(III) uptake in rice. When expressed in Xenopus laevis oocytes, OsNIP3;2 showed
a high transport activity for As(III). Quantitative real-time RT-PCR showed that
the expression of OsNIP3;2 was suppressed by 5 uM As(III), but enhanced by 20 and
100 uM As(III). Transgenic rice plants expressing OsNIP3;2pro-GUS showed that the
gene was predominantly expressed in the lateral roots and the stele region of the
primary roots. Transient expression of OsNIP3;2:GFP fusion protein in rice
protoplasts showed that the protein was localized in the plasma membrane.
Knockout of OsNIP3;2 significantly decreased As concentration in the roots, but
had little effect on shoot As concentration. Synchrotron microfocus X-ray
fluorescence showed decreased As accumulation in the stele of the lateral roots
in the mutants compared with wild-type. Our results indicate that OsNIP3;2 is
involved in As(III) uptake by lateral roots, but its contribution to As
accumulation in the shoots is limited.
PMID- 28505353
TI - Co-occurrence of mcr-1 and blaKPC-2 in a clinical isolate of Escherichia coli in
Brazil.
PMID- 28505354
TI - Psychological distress in men with prostate cancer and their partners before and
after cancer diagnosis: a longitudinal study.
AB - Objective: To examine the relative risk of psychological distress of men with
prostate cancer and their partners during the period before and after prostate
cancer diagnosis compared with men without prostate cancer and their partners.
Methods: The participants reported questionnaires on psychological distress at
four time points: before prostate cancer biopsy, and at 1, 3 and 6 months
following prostate cancer diagnosis. We performed multiple logistic regression
analyses to examine the relative risk of psychological distress. Results: A total
of 115 couples answered the questionnaires at all four time points. Men with
prostate cancer showed a significantly higher risk of psychological distress
compared to men without prostate cancer at 1 (odds ratio [OR] = 4.8, 95%
confidence interval [CI] = 1.9-13.1), 3 (OR = 3.2, 95% CI = 1.1-10.2) and 6
months following prostate cancer diagnosis (OR = 6.9, 95% CI = 2.3-25.7). Their
partners showed a significantly higher risk of psychological distress compared to
the partners of men without prostate cancer at 1 month following prostate cancer
diagnosis (OR = 2.6, 95% CI = 1.1-6.6). Conclusions: Men with prostate cancer
showed psychological distress during the 6 months following the cancer diagnosis.
Their partners also showed psychological distress at 1 month following the cancer
diagnosis. Inviting both men with prostate cancer and their partners to speak to
their concerns, empathizing with them, finding the solutions together and
monitoring of their psychological status regularly should be regarded as
important following prostate cancer diagnosis.
PMID- 28505357
TI - Resilience and Vulnerability Factors When Pain is Acute as Predictors of
Disability: Findings From a Two-Year Longitudinal Study.
AB - Objective: To investigate the predictive power of resilience and vulnerability
factors in relation to pain-related disability. Design: A two-year prospective
study investigated whether back pain-related disability was predicted by the
following variables, measured when pain was acute: 1) pain-related disability, 2)
pain intensity, 3) depression, 4) fear avoidance beliefs, 5) anxiety sensitivity,
and 6) resilience. Methods: Two hundred thirty-two patients treated in five
primary care centers participated in this study. They were assessed at baseline
during an acute back pain episode and at six, 12, 18, and 24 months. Ninety-nine
patients completed all the assessment sessions. Linear mixed models were used to
examine the trajectory of disability across the measurement occasions and its
association with the predictors. Results: Individuals who had higher scores of
disability and pain intensity when pain was acute also had higher scores of
disability six months later; moreover, the increase in disability was greater
over time in comparison with individuals with lower scores in disability and pain
intensity when pain was acute. Individuals who had reported greater levels of
fear avoidance beliefs when pain was acute also reported greater scores of
disability six months later; however, no differences were found in the rate of
change in disability. No associations were found between initial disability or
rate of change and resilience, anxiety sensitivity, or depression. Conclusions:
Patients with acute back pain who show high levels of pain-related disability,
pain intensity, and fear avoidance beliefs are at risk of developing back pain
related disability and should be the target of a preventive intervention.
PMID- 28505355
TI - Uncovering the neuroanatomical correlates of cognitive, affective and conative
theory of mind in paediatric traumatic brain injury: a neural systems
perspective.
AB - Deficits in theory of mind (ToM) are common after neurological insult acquired in
the first and second decade of life, however the contribution of large-scale
neural networks to ToM deficits in children with brain injury is unclear. Using
paediatric traumatic brain injury (TBI) as a model, this study investigated the
sub-acute effect of paediatric traumatic brain injury on grey-matter volume of
three large-scale, domain-general brain networks (the Default Mode Network, DMN;
the Central Executive Network, CEN; and the Salience Network, SN), as well as two
domain-specific neural networks implicated in social-affective processes (the
Cerebro-Cerebellar Mentalizing Network, CCMN and the Mirror Neuron/Empathy
Network, MNEN). We also evaluated prospective structure-function relationships
between these large-scale neural networks and cognitive, affective and conative
ToM. 3D T1- weighted magnetic resonance imaging sequences were acquired sub
acutely in 137 children [TBI: n = 103; typically developing (TD) children: n =
34]. All children were assessed on measures of ToM at 24-months post-injury.
Children with severe TBI showed sub-acute volumetric reductions in the CCMN, SN,
MNEN, CEN and DMN, as well as reduced grey-matter volumes of several hub regions
of these neural networks. Volumetric reductions in the CCMN and several of its
hub regions, including the cerebellum, predicted poorer cognitive ToM. In
contrast, poorer affective and conative ToM were predicted by volumetric
reductions in the SN and MNEN, respectively. Overall, results suggest that
cognitive, affective and conative ToM may be prospectively predicted by
individual differences in structure of different neural systems-the CCMN, SN and
MNEN, respectively. The prospective relationship between cerebellar volume and
cognitive ToM outcomes is a novel finding in our paediatric brain injury sample
and suggests that the cerebellum may play a role in the neural networks important
for ToM. These findings are discussed in relation to neurocognitive models of
ToM. We conclude that detection of sub-acute volumetric abnormalities of large
scale neural networks and their hub regions may aid in the early identification
of children at risk for chronic social-cognitive impairment.
PMID- 28505356
TI - Distinct Helper T Cell Type 1 and 2 Responses Associated With Malaria Protection
and Risk in RTS,S/AS01E Vaccinees.
AB - Background: The RTS,S/AS01E malaria vaccine has moderate efficacy, lower in
infants than children. Current efforts to enhance RTS,S/AS01E efficacy would
benefit from learning about the vaccine-induced immunity and identifying
correlates of malaria protection, which could, for instance, inform the choice of
adjuvants. Here, we sought cellular immunity-based correlates of malaria
protection and risk associated with RTS,S/AS01E vaccination. Methods: We
performed a matched case-control study nested within the multicenter African
RTS,S/AS01E phase 3 trial. Children and infant samples from 57 clinical malaria
cases (32 RTS,S/25 comparator vaccinees) and 152 controls without malaria (106
RTS,S/46 comparator vaccinees) were analyzed. We measured 30 markers by Luminex
following RTS,S/AS01E antigen stimulation of cells 1 month postimmunization.
Crude concentrations and ratios of antigen to background control were analyzed.
Results: Interleukin (IL) 2 and IL-5 ratios were associated with RTS,S/AS01E
vaccination (adjusted P <= .01). IL-5 circumsporozoite protein (CSP) ratios, a
helper T cell type 2 cytokine, correlated with higher odds of malaria in
RTS,S/AS01E vaccinees (odds ratio, 1.17 per 10% increases of CSP ratios; P value
adjusted for multiple testing = .03). In multimarker analysis, the helper T cell
type 1 (TH1)-related markers interferon-gamma, IL-15, and granulocyte-macrophage
colony-stimulating factor protected from subsequent malaria, in contrast to IL-5
and RANTES, which increased the odds of malaria. Conclusions: RTS,S/AS01E-induced
IL-5 may be a surrogate of lack of protection, whereas TH1-related responses may
be involved in protective mechanisms. Efforts to develop second-generation
vaccine candidates may concentrate on adjuvants that modulate the immune system
to support enhanced TH1 responses and decreased IL-5 responses.
PMID- 28505358
TI - Hijab and Depression: Does the Islamic Practice of Veiling Predict Higher Levels
of Depressive Symptoms?
AB - Hijab or veiling is commonly practiced by Muslim women but remains controversial
in the broader secular society. Some Western feminists argue that veiling is an
oppressive behavior that negatively affects women by, for example, engendering
depression. This article tests this hypothesis with a national sample of American
Muslim women (N = 194). The results of the regression analysis did not support
the hypothesis. Indeed, women who veiled more frequently reported lower, rather
than higher, levels of depressive symptoms. In other words, wearing the hijab
appears to be a protective factor in the area of depression. Given the prevalence
of depression among women, the results have important implications for practice
with Muslim women at both the micro and the macro levels.
PMID- 28505360
TI - Comparative total and unbound pharmacokinetics of cefazolin administered by bolus
versus continuous infusion in patients undergoing major surgery: a randomized
controlled trial.
AB - Background.: Perioperative administration of cefazolin reduces the incidence of
perioperative infections. Intraoperative re-dosing of cefazolin is commonly given
between 2 and 5 h after the initial dose. This study was undertaken to determine
whether intraoperative continuous infusions of cefazolin achieve better
probability of target attainment (PTA) and fractional target attainment (FTA)
than intermittent dosing. Methods.: Patients undergoing major surgery received
cefazolin 2 g before surgical incision. They were subsequently randomized to
receive either an intermittent bolus (2 g every 4 h) or continuous infusion (500
mg h -1 ) of cefazolin until skin closure. Blood samples were analysed for total
and unbound cefazolin concentrations using a validated chromatographic method.
Population pharmacokinetic modelling was performed using Pmetrics (r) software.
Calculations of PTA and FTA were performed for common pathogens. Results.: Ten
patients were enrolled in each arm. A two-compartment linear model best described
the time course of the total plasma cefazolin concentrations. The covariates that
improved the model were body weight and creatinine clearance. Protein binding
varied with time [mean (range) 69 (44-80)%] with a fixed 21% unbound value of
cefazolin used for the simulations (120 min post-initial dosing). Mean ( sd )
central volume of distribution was 5.73 (2.42) litres, and total cefazolin
clearance was 4.72 (1.1) litres h -1 . Continuous infusions of cefazolin
consistently achieved better drug exposures and FTA for different weight and
creatinine clearances, particularly for less susceptible pathogens. Conclusions.:
Our study demonstrates that intraoperative continuous infusions of cefazolin
increase the achievement of target plasma concentrations, even with lower
infusion doses. Renal function and body weight are important when considering the
need for alternative dosing regimens. Clinical trial registration.: NCT02058979.
PMID- 28505359
TI - Thoracoscopic anatomical lung segmentectomy using 3D computed tomography
simulation without tumour markings for non-palpable and non-visualized small lung
nodules.
AB - OBJECTIVES: Although wedge resection can be curative for small lung tumours,
tumour marking is sometimes required for resection of non-palpable or visually
undetectable lung nodules as a method for identification of tumours. Tumour
marking sometimes fails and occasionally causes serious complications. We have
performed many thoracoscopic segmentectomies using 3D computed tomography
simulation for undetectable small lung tumours without any tumour markings. The
aim of this study was to investigate whether thoracoscopic segmentectomy planned
with 3D computed tomography simulation could precisely remove non-palpable and
visually undetectable tumours. METHODS: Between January 2012 and March 2016, 58
patients underwent thoracoscopic segmentectomy using 3D computed tomography
simulation for non-palpable, visually undetectable tumours. Surgical outcomes
were evaluated. RESULTS: A total of 35, 14 and 9 patients underwent
segmentectomy, subsegmentectomy and segmentectomy combined with adjacent
subsegmentectomy, respectively. All tumours were correctly resected without
tumour marking. The median tumour size and distance from the visceral pleura was
14 +/- 5.2 mm (range 5-27 mm) and 11.6 mm (range 1-38.8 mm), respectively. Median
values related to the procedures were operative time, 176 min (range 83-370 min);
blood loss, 43 ml (range 0-419 ml); duration of chest tube placement, 1 day
(range 1-8 days); and postoperative hospital stay, 5 days (range 3-12 days). Two
cases were converted to open thoracotomy due to bleeding. Three cases required
pleurodesis for pleural fistula. No recurrences occurred during the mean follow
up period of 44.4 months (range 5-53 months). CONCLUSIONS: Thoracoscopic
segmentectomy using 3D computed tomography simulation was feasible and could be
performed to resect undetectable tumours with no tumour markings.
PMID- 28505361
TI - The possible evolution and future of CO2-concentrating mechanisms.
AB - CO2-concentrating mechanisms (CCMs), based either on active transport of
inorganic carbon (biophysical CCMs) or on biochemistry involving supplementary
carbon fixation into C4 acids (C4 and CAM), play a major role in global primary
productivity. However, the ubiquitous CO2-fixing enzyme in autotrophs, Rubisco,
evolved at a time when atmospheric CO2 levels were very much higher than today
and O2 was very low and, as CO2 and O2 approached (by no means monotonically),
today's levels, at some time subsequently many organisms evolved a CCM that
increased the supply of CO2 and decreased Rubisco oxygenase activity. Given that
CO2 levels and other environmental factors have altered considerably between when
autotrophs evolved and the present day, and are predicted to continue to change
into the future, we here examine the drivers for, and possible timing of,
evolution of CCMs. CCMs probably evolved when CO2 fell to 2-16 times the present
atmospheric level, depending on Rubisco kinetics. We also assess the effects of
other key environmental factors such as temperature and nutrient levels on CCM
activity and examine the evidence for evolutionary changes in CCM activity and
related cellular processes as well as limitations on continuity of CCMs through
environmental variations.
PMID- 28505364
TI - Classification of Patients With GH Disorders May Vary According to the IGF-I
Assay.
AB - Context: Insulinlike growth factor I (IGF-I) measurement is essential for the
diagnosis and management of growth hormone (GH) disorders. However, patient
classification may vary substantially according to the assay technique.
Objective: We compared individual patient data and classifications obtained with
six different IGF-I assay kits in a group of patients with various GH disorders.
Design: In this cross-sectional study, we measured IGF-I with six immunoassays in
102 patients with active or treated acromegaly or GH deficiency. IGF-I normative
data previously established for the same six assay kits were used to classify the
patients (high, low, or normal IGF-I levels), using both raw data and standard
deviation scores (SDSs). Pairwise concordance between assays was assessed with
Bland-Altman plots and with the percentage of observed agreement and the weighted
kappa coefficient for categorized IGF-I SDS. Results: We observed marked
variability both across each individual's IGF-I raw data and across IGF-I SDS
values obtained with each of the six immunoassays. Pairwise concordance between
assay values, as assessed with the weighted kappa coefficient, ranged from 0.50
(moderate) to 0.81 (excellent). Conclusion: Even when using normative data
obtained in the same large population of healthy subjects and when using
calculated IGF-I SDSs, agreement among IGF-I assay methods is only moderate to
good. Differences in assay performance must be taken into account when evaluating
and monitoring patients with GH disorders. This argues for the use of the same
IGF-I assay for a given patient throughout follow-up.
PMID- 28505363
TI - Impact of high iron intake on cognition and neurodegeneration in humans and in
animal models: a systematic review.
AB - Context: Accumulation of brain iron is linked to aging and protein-misfolding
neurodegenerative diseases. High iron intake may influence important brain health
outcomes in later life. Objective: The aim of this systematic review was to
examine evidence from animal and human studies of the effects of high iron intake
or peripheral iron status on adult cognition, brain aging, and neurodegeneration.
Data Sources: MEDLINE, Scopus, CAB Abstracts, the Cochrane Central Register of
Clinical Trials, and OpenGrey databases were searched. Study Selection: Studies
investigating the effect of elevated iron intake at all postnatal life stages in
mammalian models and humans on measures of adult brain health were included. Data
Extraction: Data were extracted and evaluated by two authors independently, with
discrepancies resolved by discussion. Neurodegenerative disease diagnosis and/or
behavioral/cognitive, biochemical, and brain morphologic findings were used to
study the effects of iron intake or peripheral iron status on brain health. Risk
of bias was assessed for animal and human studies. PRISMA guidelines for
reporting systematic reviews were followed. Results: Thirty-four preclinical and
14 clinical studies were identified from database searches. Thirty-three
preclinical studies provided evidence supporting an adverse effect of
nutritionally relevant high iron intake in neonates on brain-health-related
outcomes in adults. Human studies varied considerably in design, quality, and
findings; none investigated the effects of high iron intake in neonates/infants.
Conclusions: Human studies are needed to verify whether dietary iron intake
levels used in neonates/infants to prevent iron deficiency have effects on brain
aging and neurodegenerative disease outcomes.
PMID- 28505366
TI - Bacterioplankton assemblages in coastal ponds reflect the influence of hydrology
and geomorphological setting.
AB - The factors that shape microbial community assembly in aquatic ecosystems have
been widely studied; yet it is still unclear how distinct communities within a
connected landscape influence one another. Coastal lakes are recipients of, and
thus are connected to, both marine and terrestrial environments. Thus, they may
host microbial assemblages that reflect the relative degree of influence by, and
connectivity to, either system. In order to address this idea, we interrogated
microbial community diversity at 49 sites in seven ponds in two seasons in the
Lake MacLeod basin, a system fed by seawater flowing inland through underground
karst. Environmental and spatial variation within ponds explain <9% of the
community structure, while identity of the pond that samples were taken from
explains 50% of community variation. That is, ponds each host distinct
assemblages despite similarities in size, environment and position in the
landscape, indicating a dominant role for local species sorting. The ponds
contain a substantial amount of previously unknown microbial taxa, reflecting the
unusual nature of this inland system. Rare marine taxa, possibly dispersed from
seawater assemblages via the underground karst connection, are abundant within
the inland system, suggesting an important role for regional dispersal within the
metacommunities.
PMID- 28505362
TI - Lipidomic profiling reveals distinct differences in plasma lipid composition in
healthy, prediabetic, and type 2 diabetic individuals.
AB - The relationship between dyslipidemia and type 2 diabetes mellitus (T2D) has been
extensively reported, but the global lipid profiles, especially in the East Asia
population, associated with the development of T2D remain to be characterized.
Liquid chromatography coupled to tandem mass spectrometry was applied to detect
the global lipidome in the fasting plasma of 293 Chinese individuals, including
114 T2D patients, 81 prediabetic subjects, and 98 individuals with normal glucose
tolerance (NGT). Both qualitative and quantitative analyses revealed a gradual
change in plasma lipid features with T2D patients exhibiting characteristics
close to those of prediabetic individuals, whereas they differed significantly
from individuals with NGT. We constructed and validated a random forest
classifier with 28 lipidomic features that effectively discriminated T2D from NGT
or prediabetes. Most of the selected features significantly correlated with
diabetic clinical indices. Hydroxybutyrylcarnitine was positively correlated with
fasting plasma glucose, 2-hour postprandial glucose, glycated hemoglobin, and
insulin resistance index (HOMA-IR). Lysophosphatidylcholines such as
lysophosphatidylcholine (18:0), lysophosphatidylcholine (18:1), and
lysophosphatidylcholine (18:2) were all negatively correlated with HOMA-IR. The
altered plasma lipidome in Chinese T2D and prediabetic subjects suggests that
lipid features may play a role in the pathogenesis of T2D and that such features
may provide a basis for evaluating risk and monitoring disease development.
PMID- 28505365
TI - Allograft Inflammatory Factor-1 Links T-Cell Activation, Interferon Response, and
Macrophage Activation in Chronic Kawasaki Disease Arteritis.
AB - Background: Kawasaki disease (KD) is widely viewed as an acute arteritis.
However, our pathologic studies show that chronic coronary arteritis can persist
long after disease onset and is closely linked with arterial stenosis.
Transcriptome profiling of acute KD arteritis tissues revealed upregulation of T
lymphocyte, type I interferon, and allograft inflammatory factor-1 (AIF1) genes.
We determined whether these immune responses persist in chronic KD arteritis, and
we investigated the role of AIF1 in these responses. Methods: Gene expression in
chronic KD and childhood control arteries was determined by real-time reverse
transcriptase polymerase chain reaction, and arterial protein expression was
determined by immunohistochemistry and immunofluorescence. Allograft inflammatory
factor-1 small-interfering ribonucleic acid macrophage treatment was performed to
investigate the role of AIF1 in macrophage and T lymphocyte activation. Results:
Allograft inflammatory factor-1 protein was highly expressed in stenotic KD
arteries and colocalized with the macrophage marker CD68. T lymphocyte and
interferon pathway genes were significantly upregulated in chronic KD coronary
artery tissues. Alpha interferon-induced macrophage expression of CD80 and major
histocompatibility complex class II was dependent on AIF1, and macrophage
expression of AIF1 was required for antigen-specific T lymphocyte activation.
Conclusions: Allograft inflammatory factor-1, originally identified in
posttransplant arterial stenosis, is markedly upregulated in KD stenotic arterial
tissues. T lymphocyte and type I interferon responses persist in chronic KD
arteritis. Allograft inflammatory factor-1 may play multiple roles linking type I
interferon response, macrophage activation, and antigen-specific T lymphocyte
activation. These results suggest the likely importance of lymphocyte-myeloid
cell cross-talk in the pathogenesis of KD arteritis and can inform selection of
new immunotherapies for clinical trials in high-risk KD children.
PMID- 28505367
TI - Effect of health information exchange on recognition of medication discrepancies
is interrupted when data charges are introduced: results of a cluster-randomized
controlled trial.
AB - Objectives: To determine the effect of health information exchange (HIE) on
medication prescribing for hospital inpatients in a cluster-randomized controlled
trial, and to examine the prescribing effect of availability of information from
a large pharmacy insurance plan in a natural experiment. Methods: Patients
admitted to an urban hospital received structured medication reconciliation by an
intervention pharmacist with (intervention) or without (control) access to a
regional HIE. The HIE contained prescribing information from the largest
hospitals and pharmacy insurance plan in the region for the first 10 months of
the study, but only from the hospitals for the last 21 months, when data charges
were imposed by the insurance plan. The primary endpoint was discrepancies
between preadmission and inpatient medication regimens, and secondary endpoints
included adverse drug events (ADEs) and proportions of rectified discrepancies.
Results: Overall, 186 and 195 patients were assigned to intervention and control,
respectively. Patients were 60 years old on average and took a mean of 7
medications before admission. There was no difference between intervention and
control in number of risk-weighted discrepancies (6.4 vs 5.8, P = .452),
discrepancy-associated ADEs (0.102 vs 0.092 per admission, P = .964), or
rectification of discrepancies (0.026 vs 0.036 per opportunity, P = .539).
However, patients who received medication reconciliation with pharmacy insurance
data available had more risk-weighted medication discrepancies identified than
those who received usual care (8.0 vs 5.9, P = .038). Discussion and Conclusion:
HIE may improve outcomes of medication reconciliation. Charging for access to
medication information interrupts this effect. Efforts are needed to understand
and increase prescribers' rectification of medication discrepancies.
PMID- 28505368
TI - Editor's Highlight: Farnesoid X Receptor Protects Against Low-Dose Carbon
Tetrachloride-Induced Liver Injury Through the Taurocholate-JNK Pathway.
AB - Hepatotoxicity is of major concern for humans exposed to industrial chemicals and
drugs. Disruption of farnesoid X receptor (FXR), a master regulator of bile acid
(BA) metabolism, enhanced the sensitivity to liver injury in mice after toxicant
exposure, but the precise mechanism remains unclear. In this study, the
interconnection between BA metabolism, FXR, and chemically induced hepatotoxicity
was investigated using metabolomics, Fxr-null mice (Fxr-/-) and hepatocytes, and
recombinant adenoviruses. A single low-dose intraperitoneal injection of carbon
tetrachloride (CCl4), an inducer of acute hepatitis in mice, resulted in more
severe hepatocyte damage and higher induction of pro-inflammatory mediators, such
as chemokine (C-C motif) ligand 2 (Ccl2), in Fxr-/-. Serum metabolomics analysis
revealed marked increases in circulating taurocholate (TCA) and tauro-beta
muricholate (T-beta-MCA) in these mice, and forced expression of bile salt export
protein (BSEP) by recombinant adenovirus in Fxr-/- ameliorated CCl4-induced liver
damage. Treatment of Fxr-null hepatocytes with TCA, but not T-beta-MCA,
significantly increased c-Jun-N-terminal kinase (JNK) activation and Ccl2 mRNA
levels, and up-regulation of Ccl2 mRNA was attenuated by co-treatment with a JNK
inhibitor SP600125, indicating that TCA directly amplifies hepatocyte
inflammatory signaling mainly mediated by JNK under FXR-deficiency. Additionally,
pretreatment with SP600125 or restoration of FXR expression in liver by use of
recombinant adenovirus, attenuated CCl4-induced liver injury. Collectively, these
results suggest that the TCA-JNK axis is likely associated with increased
susceptibility to CCl4-induced acute liver injury in Fxr-/-, and provide clues to
the mechanism by which FXR and its downstream gene targets, such as BSEP,
protects against chemically induced hepatotoxicity.
PMID- 28505370
TI - The complete nucleotide sequence of an IncP-2 megaplasmid unveils a mosaic
architecture comprising a putative novel blaVIM-2-harbouring transposon in
Pseudomonas aeruginosa.
AB - Objectives: In Pseudomonas aeruginosa , bla VIM-2 has been mostly associated with
a chromosomal location and rarely with a plasmid backbone. Until now, only three
complete bla VIM-2 -carrying plasmid sequences have been described in this
species. Here we explore the modular structure of pJB37, the first bla VIM-2
carrying megaplasmid described in P. aeruginosa . Methods: The complete
nucleotide sequence of plasmid pJB37 was determined with an Illumina HiSeq, with
de novo assembly by SPAdes, annotation by RAST and searching for antimicrobial
resistance genes and virulence factors. Conjugation assays were conducted.
Results: Megaplasmid pJB37 (464 804 bp long and GC content of 57.2%) comprised:
an IncP-2 repA-oriV-parAB region; a conjugative transfer region ( traF , traG ,
virD2 and trbBCDEJLFGI genes); Tn 6356 , a new putative bla VIM-2 -carrying
transposon; heavy metal (mercury and tellurite) resistance operons; and an
arsenal of virulence genes. Plasmid pJB37 was transferable by conjugation to a
spontaneous rifampicin-resistant mutant of P. aeruginosa PAO1. Here, a bla VIM-2
harbouring In58 integron was associated with a new complex transposable
structure, herein named Tn 6356 , suggesting that In58 was most likely acquired
by insertion of this element. Conclusions: The mosaic arrangement exhibited by
the pJB37 IncP-2 megaplasmid, which highlights the vast assembly potential of
distinct genetic elements in a Pseudomonas widespread plasmid platform, gives new
insights into bacterial adaptation and evolution.
PMID- 28505369
TI - Identification of an Early Male-Killing Agent in the Oriental Tea Tortrix, Homona
magnanima.
AB - Arthropods are frequently infected with inherited symbionts, which sometimes
confer fitness benefits on female hosts or manipulate host reproduction. Early
male killing, in which infected males die during embryogenesis, is induced by
some bacteria, such as Wolbachia and Spiroplasma. A female-biased sex ratio has
been found in Homona magnanima, collected from a tea plantation in Japan. Here,
we examined the male-killing trait in H. magnanima and identified the agent that
induces early male killing. The sex ratio distortion (SR) strain produced only
females and no males, and its egg hatch rate was significantly lower than that of
the normal (N) strain. The N strain was infected with only Wolbachia, whereas the
SR strain was infected with both Wolbachia and Spiroplasma. Antibiotic treatment
with 0.10% tetracycline restored the 1:1 sex ratio in the SR strain. Females
treated with 0.05% tetracycline were positive for Spiroplasma but not for
Wolbachia and showed a female-biased sex ratio, whereas Wolbachia-positive
females did not revert to male killing. When inoculated with a homogenate of the
SR strain female, females infected with only Spiroplasma produced female-biased
offspring. Sequence analysis of the 16S rRNA gene revealed that Spiroplasma sp.
of H. magnanima belonged to the ixodetis clade. These results indicate that
Spiroplasma was responsible for male killing in H. magnanima. Late male killing
is induced in H. magnanima by an RNA-like virus, and therefore this is the first
case in which different male-killing agents expressed at different times in the
life cycle have been found within one host species.
PMID- 28505371
TI - The ARM Domain of ARMADILLO-REPEAT KINESIN 1 is Not Required for Microtubule
Catastrophe But Can Negatively Regulate NIMA-RELATED KINASE 6 in Arabidopsis
thaliana.
AB - Microtubules are dynamic filaments, the assembly and disassembly of which are
under precise control of various associated proteins, including motor proteins
and regulatory enzymes. In Arabidopsis thaliana, two such proteins are the
ARMADILLO-REPEAT KINESIN 1 (ARK1), which promotes microtubule disassembly, and
the NIMA-RELATED KINASE 6 (NEK6), which has a role in organizing microtubule
arrays. Previous yeast two-hybrid and in vitro pull-down assays determined that
NEK6 can interact with ARK1 through the latter protein's Armadillo-repeat (ARM)
cargo domain. To explore the function of the ARM domain, we generated fluorescent
reporter fusion proteins to ARK1 lacking the ARM domain (ARK1DeltaARM-GFP) and to
the ARM domain alone (ARM-GFP). Both of these constructs strongly associated with
the growing plus ends of microtubules, but only ARK1DeltaARM-GFP was capable of
inducing microtubule catastrophe and rescuing the ark1-1 root hair phenotype.
These results indicate that neither the ARM domain nor NEK6's putative
interaction with it is required for ARK1 to induce microtubule catastrophe. In
further exploration of the ARK1-NEK6 relationship, we demonstrated that, despite
evidence that NEK6 can phosphorylate ARK1 in vitro, the in vivo distribution and
function of ARK1 were not affected by the loss of NEK6, and vice versa. Moreover,
NEK6 and ARK1 were found to have overlapping but non-identical distribution on
microtubules, and hormone treatments known to affect NEK6 activity did not
stimulate interaction. These findings suggest that ARK1 and NEK6 function
independently in microtubule dynamics and cell morphogenesis. Despite the results
of this functional analysis, we found that overexpression of the ARM domain led
to complete loss of NEK6 transcription, suggesting that the ARM domain might have
a regulatory role in NEK6 expression.
PMID- 28505372
TI - Madumycin II inhibits peptide bond formation by forcing the peptidyl transferase
center into an inactive state.
AB - The emergence of multi-drug resistant bacteria is limiting the effectiveness of
commonly used antibiotics, which spurs a renewed interest in revisiting older and
poorly studied drugs. Streptogramins A is a class of protein synthesis inhibitors
that target the peptidyl transferase center (PTC) on the large subunit of the
ribosome. In this work, we have revealed the mode of action of the PTC inhibitor
madumycin II, an alanine-containing streptogramin A antibiotic, in the context of
a functional 70S ribosome containing tRNA substrates. Madumycin II inhibits the
ribosome prior to the first cycle of peptide bond formation. It allows binding of
the tRNAs to the ribosomal A and P sites, but prevents correct positioning of
their CCA-ends into the PTC thus making peptide bond formation impossible. We
also revealed a previously unseen drug-induced rearrangement of nucleotides U2506
and U2585 of the 23S rRNA resulting in the formation of the U2506*G2583 wobble
pair that was attributed to a catalytically inactive state of the PTC. The
structural and biochemical data reported here expand our knowledge on the
fundamental mechanisms by which peptidyl transferase inhibitors modulate the
catalytic activity of the ribosome.
PMID- 28505374
TI - Comment on: Trimethoprim/sulfamethoxazole versus vancomycin in the treatment of
healthcare/ventilator-associated MRSA pneumonia: a case-control study.
PMID- 28505373
TI - Gene Duplication Leads to Altered Membrane Topology of a Cytochrome P450 Enzyme
in Seed Plants.
AB - Evolution of the phenolic metabolism was critical for the transition of plants
from water to land. A cytochrome P450, CYP73, with cinnamate 4-hydroxylase (C4H)
activity, catalyzes the first plant-specific and rate-limiting step in this
pathway. The CYP73 gene is absent from green algae, and first detected in
bryophytes. A CYP73 duplication occurred in the ancestor of seed plants and was
retained in Taxaceae and most angiosperms. In spite of a clear divergence in
primary sequence, both paralogs can fulfill comparable cinnamate hydroxylase
roles both in vitro and in vivo. One of them seems dedicated to the biosynthesis
of lignin precursors. Its N-terminus forms a single membrane spanning helix and
its properties and length are highly constrained. The second is characterized by
an elongated and variable N-terminus, reminiscent of ancestral CYP73s. Using as
proxies the Brachypodium distachyon proteins, we show that the elongation of the
N-terminus does not result in an altered subcellular localization, but in a
distinct membrane topology. Insertion in the membrane of endoplasmic reticulum
via a double-spanning open hairpin structure allows reorientation to the lumen of
the catalytic domain of the protein. In agreement with participation to a
different functional unit and supramolecular organization, the protein displays
modified heme proximal surface. These data suggest the evolution of divergent C4H
enzymes feeding different branches of the phenolic network in seed plants. It
shows that specialization required for retention of gene duplicates may result
from altered protein topology rather than change in enzyme activity.
PMID- 28505377
TI - Performance of glomerular filtration rate estimating equations in a community
based sample of Blacks and Whites: the multiethnic study of atherosclerosis.
AB - Background: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
equations are recommended for glomerular filtration rate (GFR) estimation in the
general population. They have not been evaluated in community-based populations,
including Blacks at higher levels of GFR, but are commonly applied in such
populations. Methods: In an ancillary study of Multi-Ethnic Study of
Atherosclerosis conducted at one site, we evaluated the performance of the CKD
EPI equations for creatinine (eGFRcr), cystatin C (eGFRcys) or the combination
(eGFRcr-cys) compared with GFR measured as plasma clearance of iohexol. Results:
Among 294 participants, the mean age was 71 (SD 9) years, 47% were Black, 48%
were women and the mean measured GFR (mGFR) was 72.6 (SD 18.8) mL/min/1.73 m2.
The CKD-EPI equations overestimated mGFR with a larger median bias for eGFRcr and
eGFRcr-cys than eGFRcys [-8.3 (95% confidence interval -9.7, -6.5), -7.8 (-9.2,
6.2) and -3.7 (-5.0, -1.8) mL/min/1.73 m2, respectively], with smaller bias for
those with lower compared with higher eGFR and by race compared with sex.
Conclusion: The small differential bias of the CKD-EPI equation between races
suggests that they can be used in Blacks as well as Whites in older community
based adults. The large differential bias in women versus men in all equations is
in contrast to other studies and is unexplained. Further studies are required in
multiracial and multiethnic community-based cohorts, taking into account
differences in GFR measurement methods.
PMID- 28505378
TI - Overweight and abdominal obesity in women of childbearing age of Russian, Somali
and Kurdish origin and the general Finnish population.
AB - Background: Migrant background and higher parity may increase the risk of being
overweight. We compared the prevalence of overweight (body mass index >=25 kg/m2)
and abdominal obesity (waist-to-height ratio >=0.5) between non-pregnant migrant
and Finnish women aged 18-45 years. Methods: The participants were 165 Russian,
164 Somali and 179 Kurdish origin women from the cross-sectional Migrant Health
and Wellbeing study. The reference group included 388 women from the general
Finnish population. Body anthropometrics were measured. The main statistical
methods were logistic regression adjusted for sociodemographic and reproductive
variables. Results: The unadjusted prevalence of overweight and obesity,
respectively, were higher among Somali (32.9%, 30.9%, P < 0.001) and Kurdish
women (41.1%, 19.5%, P < 0.001) than among Finnish women (19.9%, 9.8%). The
adjusted odds ratios (95% CI) for overweight (including obesity) were 0.54 (0.33;
0.89) for Russian, 2.89 (1.66; 5.03) for Somali and 2.56 (1.64; 4.00) for Kurdish
women compared with Finnish women. Kurdish women had 2.96-fold (1.75; 5.00)
adjusted odds ratio for abdominal obesity compared with Finnish women. Being
parous was associated with overweight and abdominal obesity among Kurdish women.
Conclusions: Overweight and obesity were very common among Somali and Kurdish
origin women. Information on diet and physical activity in these groups is
needed.
PMID- 28505375
TI - Between a Pod and a Hard Test: The Deep Evolution of Amoebae.
AB - Amoebozoa is the eukaryotic supergroup sister to Obazoa, the lineage that
contains the animals and Fungi, as well as their protistan relatives, and the
breviate and apusomonad flagellates. Amoebozoa is extraordinarily diverse,
encompassing important model organisms and significant pathogens. Although
amoebozoans are integral to global nutrient cycles and present in nearly all
environments, they remain vastly understudied. We present a robust phylogeny of
Amoebozoa based on broad representative set of taxa in a phylogenomic framework
(325 genes). By sampling 61 taxa using culture-based and single-cell
transcriptomics, our analyses show two major clades of Amoebozoa, Discosea, and
Tevosa. This phylogeny refutes previous studies in major respects. Our results
support the hypothesis that the last common ancestor of Amoebozoa was sexual and
flagellated, it also may have had the ability to disperse propagules from a
sporocarp-type fruiting body. Overall, the main macroevolutionary patterns in
Amoebozoa appear to result from the parallel losses of homologous characters of a
multiphase life cycle that included flagella, sex, and sporocarps rather than
independent acquisition of convergent features.
PMID- 28505376
TI - Evolutionary re-wiring of p63 and the epigenomic regulatory landscape in
keratinocytes and its potential implications on species-specific gene expression
and phenotypes.
AB - Although epidermal keratinocyte development and differentiation proceeds in
similar fashion between humans and mice, evolutionary pressures have also wrought
significant species-specific physiological differences. These differences between
species could arise in part, by the rewiring of regulatory network due to changes
in the global targets of lineage-specific transcriptional master regulators such
as p63. Here we have performed a systematic and comparative analysis of the p63
target gene network within the integrated framework of the transcriptomic and
epigenomic landscape of mouse and human keratinocytes. We determined that there
exists a core set of ~1600 genomic regions distributed among enhancers and super
enhancers, which are conserved and occupied by p63 in keratinocytes from both
species. Notably, these DNA segments are typified by consensus p63 binding motifs
under purifying selection and are associated with genes involved in key
keratinocyte and skin-centric biological processes. However, the majority of the
p63-bound mouse target regions consist of either murine-specific DNA elements
that are not alignable to the human genome or exhibit no p63 binding in the
orthologous syntenic regions, typifying an occupancy lost subset. Our results
suggest that these evolutionarily divergent regions have undergone significant
turnover of p63 binding sites and are associated with an underlying inactive and
inaccessible chromatin state, indicative of their selective functional activity
in the transcriptional regulatory network in mouse but not human. Furthermore, we
demonstrate that this selective targeting of genes by p63 correlates with subtle,
but measurable transcriptional differences in mouse and human keratinocytes that
converges on major metabolic processes, which often exhibit species-specific
trends. Collectively our study offers possible molecular explanation for the
observable phenotypic differences between the mouse and human skin and broadly
informs on the prevailing principles that govern the tug-of-war between
evolutionary forces of rigidity and plasticity over transcriptional regulatory
programs.
PMID- 28505379
TI - Analysis of CFB, a cytokinin-responsive gene of Arabidopsis thaliana encoding a
novel F-box protein regulating sterol biosynthesis.
AB - Protein degradation by the ubiquitin-26S proteasome pathway is important for the
regulation of cellular processes, but the function of most F-box proteins
relevant to substrate recognition is unknown. We describe the analysis of the
gene Cytokinin-induced F-box encoding (CFB, AT3G44326), identified in a meta
analysis of cytokinin-related transcriptome studies as one of the most robust
cytokinin response genes. F-box domain-dependent interaction with the E3
ubiquitin ligase complex component ASK1 classifies CFB as a functional F-box
protein. Apart from F-box and transmembrane domains, CFB contains no known
functional domains. CFB is expressed in all plant tissues, predominantly in root
tissue. A ProCFB:GFP-GUS fusion gene showed strongest expression in the lateral
root cap and during lateral root formation. CFB-GFP fusion proteins were mainly
localized in the nucleus and the cytosol but also at the plasma membrane. cfb
mutants had no discernible phenotype, but CFB overexpressing plants showed
several defects, such as a white upper inflorescence stem, similar to the
hypomorphic cycloartenol synthase mutant cas1-1. Both CFB overexpressing plants
and cas1-1 mutants accumulated the CAS1 substrate 2,3-oxidosqualene in the white
stem tissue, the latter even more after cytokinin treatment, indicating
impairment of CAS1 function. This suggests that CFB may link cytokinin and the
sterol biosynthesis pathway.
PMID- 28505382
TI - Facile Phenylphosphinidene Transfer Reactions from Carbene-Phosphinidene Zinc
Complexes.
AB - Phosphinidenes [R-P] are convenient P1 building blocks for the synthesis of a
plethora of organophosphorus compounds. Thus far, transition-metal-complexed
phosphinidenes have been used for their singlet ground-state reactivity to
promote selective addition and insertion reactions. One disadvantage of this
approach is that after transfer of the P1 moiety to the substrate, a challenging
demetallation step is required to provide the free phosphine. We report a simple
method that enables the Lewis acid promoted transfer of phenylphosphinidene,
[PhP], from NHC=PPh adducts (NHC=N-heterocyclic carbene) to various substrates to
produce directly uncoordinated phosphorus heterocycles that are difficult to
obtain otherwise.
PMID- 28505380
TI - Potential reward reduces the adverse impact of negative distractor stimuli.
AB - Knowledge about interactions between reward and negative processing is
rudimentary. Here, we employed functional MRI to probe how potential reward
signaled by advance cues alters aversive distractor processing during perception.
Behaviorally, the influence of aversive stimuli on task performance was reduced
during the reward compared to no-reward condition. In the brain, at the task
phase, paralleling the observed behavioral pattern, we observed significant
interactions in the anterior insula and dorsal anterior cingulate cortex, such
that responses during the negative (vs neutral) condition were reduced during the
reward compared to no-reward condition. Notably, negative distractor processing
in the amygdala appeared to be independent of the reward manipulation. During the
initial cue phase, we observed increased reward-related responses in the ventral
striatum/accumbens, which were correlated with behavioral interference scores at
the subsequent task phase, revealing that participants with increased reward
related responses exhibited a greater behavioral benefit of reward in reducing
the adverse effect of negative images. Furthermore, during processing of reward
(vs no-reward) cues, the ventral striatum exhibited stronger functional
connectivity with fronto-parietal regions important for attentional control.
Together, our findings contribute to the understanding of how potential reward
influences attentional control and reduces negative distractor processing in the
human brain.
PMID- 28505383
TI - Arboreal camera trapping expands Hyla versicolor complex (Hylidae) canopy use to
new heights.
PMID- 28505381
TI - Insulin Resistance Disrupts the Interaction Between AKT and the NMDA Receptor and
the Inactivation of the CaMKIV/CREB Pathway in Minimal Hepatic Encephalopathy.
AB - Hepatic cirrhosis-induced Minimal hepatic encephalopathy (MHE) has been
characterized for cognitive dysfunction and central nervous system (CNS) insulin
resistance (IR) has been acknowledged to be closely correlated with cognitive
impairment while hepatic cirrhosis has been recognized to induce IR. Thus, this
study aimed to investigate whether CNS IR occurred in MHE and induced MHE, as
well as the underlying mechanism. We found IR in the MHE rats, an especially
decreased level of the insulin receptor (InsR), and an increased serine
phosphorylation of IRS1 in CNS. PI3K/AKT pathway signaling to the phosphorylation
of N-Methyl-d-Aspartate receptors (NMDA receptors, NRs, NR1/NR2B) and downstream
activation of the CaMKIV/CREB pathway and final production of neurotrophic
factors were triggered by insulin, but impaired in the MHE rats. Additionally,
CNS IR, memory impairment, the desensitization of the PI3K/AKT/NMDA receptor
(NR)/CaMKIV/CREB pathway and decreased production of BDNF/NT3 in MHE rats were
improved by rosiglitazone (RSG). These results suggested that IR, which induces
the deficits in the insulin-mediated PI3K/AKT/NR/CaMKIV/CREB/neurotrophin pathway
and subsequent memory decline, contributes to the pathogenesis of MHE.
PMID- 28505384
TI - A Systematic Review of the Effect of Therapists' Internalized Models of
Relationships on the Quality of the Therapeutic Relationship.
AB - OBJECTIVE: Previous reviews have found equivocal evidence of an association
between therapists' internalized relational models and the therapeutic
relationship and have neglected empirical literature based on Sullivan's notion
of introject. This review expanded upon previous reviews to examine the effect of
therapist internalized relational models on a broader conceptualization of the
therapeutic relationship. METHOD: Systematic search processes identified 22
papers measuring therapist attachment and/or introject and therapeutic
relationship: 19 on therapist attachment, 5 on introject with 2 overlapping.
RESULTS: Overall, despite heterogeneity in design and variable methodological
quality, evidence suggests that therapist attachment affects therapeutic
relationship quality, observed in client-rated evaluation, therapist negative
countertransference, empathy, and problems in therapy. Interaction effects
between client and therapist attachment style were also found. Evidence
suggesting that therapist introject also affects therapeutic relationship
quality, including therapists' manner and feelings toward their clients, was
stronger. CONCLUSION: Evidence clearly shows that therapists' internalized
relational models affect the therapeutic relationship. More research is necessary
to clarify exactly how therapist and client internalized relational models
interact and translate these findings into clinical practice.
PMID- 28505385
TI - Professional Burnout, Early Maladaptive Schemas, and Physical Health in Clinical
and Counselling Psychology Trainees.
AB - OBJECTIVE: Little is known about the personal factors that increase vulnerability
to job-related stress and burnout among psychologists in training. This study was
based on a large international sample and aimed to explore the role of early
maladaptive schemas (EMS) in predicting vulnerability to burnout, as well as
attendant effects on short-term physical health, in clinical and counseling
postgraduate psychology trainees. METHOD: An online, quantitative, cross
sectional survey method design was used to collect self-report data that measured
burnout, EMS, and physical health from 1,297 trainees. RESULTS: Only the
unrelenting standards (US) schema predicted high burnout among trainees. The most
commonly endorsed physical health symptoms were back and neck pain and tiredness,
and were more severe for those experiencing high burnout. CONCLUSION: The current
study contributes to our understanding of the role of the US EMS in the evolution
of burnout in trainees and has implications for the development of self-awareness
training programs for this population.
PMID- 28505387
TI - Interspecific combat observed among viperid snakes.
PMID- 28505388
TI - Tuning Up or Down the Critical Thickness in LaAlO3 /SrTiO3 through In Situ
Deposition of Metal Overlayers.
AB - The quasi 2D electron system (q2DES) that forms at the interface between LaAlO3
and SrTiO3 has attracted much attention from the oxide electronics community. One
of its hallmark features is the existence of a critical LaAlO3 thickness of 4
unit-cells (uc) for interfacial conductivity to emerge. In this paper, the
chemical, electronic, and transport properties of LaAlO3 /SrTiO3 samples capped
with different metals grown in a system combining pulsed laser deposition,
sputtering, and in situ X-ray photoemission spectroscopy are investigated. The
results show that for metals with low work function a q2DES forms at 1-2 uc of
LaAlO3 and is accompanied by a partial oxidation of the metal, a phenomenon that
affects the q2DES properties and triggers the formation of defects. In contrast,
for noble metals, the critical thickness is increased above 4 uc. The results are
discussed in terms of a hybrid mechanism that incorporates electrostatic and
chemical effects.
PMID- 28505386
TI - C/D-box snoRNAs form methylating and non-methylating ribonucleoprotein complexes:
Old dogs show new tricks.
AB - C/D box snoRNAs (SNORDs) are an abundantly expressed class of short, non-coding
RNAs that have been long known to perform 2'-O-methylation of rRNAs. However,
approximately half of human SNORDs have no predictable rRNA targets, and numerous
SNORDs have been associated with diseases that show no defects in rRNAs, among
them Prader-Willi syndrome, Duplication 15q syndrome and cancer. This apparent
discrepancy has been addressed by recent studies showing that SNORDs can act to
regulate pre-mRNA alternative splicing, mRNA abundance, activate enzymes, and be
processed into shorter ncRNAs resembling miRNAs and piRNAs. Furthermore, recent
biochemical studies have shown that a given SNORD can form both methylating and
non-methylating ribonucleoprotein complexes, providing an indication of the
likely physical basis for such diverse new functions. Thus, SNORDs are more
structurally and functionally diverse than previously thought, and their role in
gene expression is under-appreciated. The action of SNORDs in non-methylating
complexes can be substituted with oligonucleotides, allowing devising therapies
for diseases like Prader-Willi syndrome.
PMID- 28505389
TI - Nitrogen and phosphorus availabilities interact to modulate leaf trait scaling
relationships across six plant functional types in a controlled-environment
study.
AB - Nitrogen (N) and phosphorus (P) have key roles in leaf metabolism, resulting in a
strong coupling of chemical composition traits to metabolic rates in field-based
studies. However, in such studies, it is difficult to disentangle the effects of
nutrient supply per se on trait-trait relationships. Our study assessed how high
and low N (5 mM and 0.4 mM, respectively) and P (1 mM and 2 MUM, respectively)
supply in 37 species from six plant functional types (PTFs) affected
photosynthesis (A) and respiration (R) (in darkness and light) in a controlled
environment. Low P supply increased scaling exponents (slopes) of area-based log
log A-N or R-N relationships when N supply was not limiting, whereas there was no
P effect under low N supply. By contrast, scaling exponents of A-P and R-P
relationships were altered by P and N supply. Neither R : A nor light inhibition
of leaf R was affected by nutrient supply. Light inhibition was 26% across
nutrient treatments; herbaceous species exhibited a lower degree of light
inhibition than woody species. Because N and P supply modulates leaf trait-trait
relationships, the next generation of terrestrial biosphere models may need to
consider how limitations in N and P availability affect trait-trait relationships
when predicting carbon exchange.
PMID- 28505390
TI - Correlation between Chiral Modifier Adsorption and Enantioselectivity in
Hydrogenation Catalysis.
AB - Infrared absorption spectroscopy performed in situ at the solid-liquid interface
revealed that the adsorption on platinum supported catalysts of 1-(1-naphthyl)
ethylamine, which is used as a chiral modifier in hydrogenation catalysis, occurs
through the amine group, not the aromatic ring as is widely believed. Comparisons
were performed against a set of related modifier compounds with targeted
substitutions to help identify the key moiety involved in the adsorption. It was
determined that neither naphthalene-based modifiers without amine groups nor
those with tertiary amine moieties are capable of adsorbing on the metal surface
to any significant extent. A direct correlation was also found between the
ability of the amines to adsorb on the platinum surface and their performance as
chiral modifiers that impart enantioselectivity to the hydrogenation of alpha
keto esters such as ethyl pyruvate.
PMID- 28505391
TI - Establishment of a novel quantum dots-encoded microbead-based flow cytometric
method for quantification of soluble FcepsilonRIalpha in serum.
AB - The soluble form of the transmembrane glycoprotein, FcepsilonRIalpha which
corresponds to the high-affinity receptor for IgE, is found in serum. Growing
evidence suggests the pathogenic role of IgE and FcepsilonRI in systemic lupus
erythematosus (SLE). The goal of this study is to develop a sensitive and
standardized cytometric assay for quantification of sFcepsilonRIalpha. A membrane
emulsification technique was utilized to incorporate CuInS2 /ZnS quantum dots and
Fe3 O4 nanoparticles into poly (styrene-co-maleic anhydride) microbeads. The
beads were then carboxylated and coated with capture antibody monoclonal anti
human FcepsilonRIalpha. This antibody binds to FcepsilonRIalpha but does not
block the binding of FcepsilonRIalpha to IgE. After incubation with standards or
serum samples, the microbeads were incubated with excessive native human IgE,
followed by incubation with Phycoerythrin (PE) conjugated anti-human IgE. The
resulting quantum dot microbeads were gated, and sFcepsilonRIalpha quantification
was analyzed based on PE fluorescence intensity. The method exhibited good
linearity (R2 > 0.99), and the limit of detection was established at 0.29 ng/mL
with the dynamic range of up to 200 ng/mL. The precision of the assay validated
by intra- and inter-assay variability met the acceptance criteria with the mean
recovery falling within 80-110% of the theoretical concentration and a
corresponding CV < 20%. We tested 149 serum samples which 89 were from SLE
patients and 60 were from healthy volunteers. For the first time, we detected an
increased sFcepsilonRIalpha level in the serum of SLE patients, which was
confirmed by a commercial ELISA kit. Compared to ELISA, this novel method is more
sensitive and efficient. It allows for the simple comparative analysis of
sFcepsilonRIalpha levels in health and disease. (c) 2017 International Society
for Advancement of Cytometry.
PMID- 28505392
TI - Beneficial effects of ginger Zingiber officinale Roscoe on obesity and metabolic
syndrome: a review.
AB - In recent years, metabolic syndromes (MetSs), including diabetes mellitus,
dyslipidemia, and cardiovascular diseases, have become a common health problem in
both developed and developing countries. Accumulating data have suggested that
traditional herbs might be able to provide a wide range of remedies in prevention
and treatment of MetSs. Ginger (Zingiber officinale Roscoe, Zingiberaceae) has
been documented to ameliorate hyperlipidemia, hyperglycemia, oxidative stress,
and inflammation. These beneficial effects are mediated by transcription factors,
such as peroxisome proliferator-activated receptors, adenosine monophosphate
activated protein kinase, and nuclear factor kappaB. This review focuses on
recent findings regarding the beneficial effects of ginger on obesity and related
complications in MetS and discusses its potential mechanisms of action. This
review provides guidance for further applications of ginger for personalized
nutrition and medicine.
PMID- 28505393
TI - The science behind One Health: at the interface of humans, animals, and the
environment.
AB - Humans face a grand quality-of-life challenge as growing demands for resources
for an ever-expanding population threaten the existence of wildlife populations,
degrade land, and pollute air and water. Public investment and policy decisions
that will shape future interactions of humans, animals, and the environment need
scientific input to help find common ground for durable and sustainable success.
The Second International Conference on One Medicine One Science brought together
a broad range of scientists, trainees, regulatory authorities, and health experts
from 34 countries to inform and discuss the human impacts of air quality; the
complexities of water quality, access, and conflicts; the opportunities and
uncertainties in precision medicine; and the role of science communication in
health policy formulation. Workshops focused on the roles and development of
physician-scientists and multidisciplinary teams in complex problem solving, Big
Data tools for analysis and visualization, international policy development
processes, and health models that benefit animals and humans. Key realizations
were that local and regional health challenges at the interface of humans,
animals, and the environment are variations of the same overarching conflicts and
that international gatherings provide new opportunities for investigation and
policy development that are broadly applicable.
PMID- 28505394
TI - 1,2,4-Triazole-3-thione Compounds as Inhibitors of Dizinc Metallo-beta
lactamases.
AB - Metallo-beta-lactamases (MBLs) cause resistance of Gram-negative bacteria to beta
lactam antibiotics and are of serious concern, because they can inactivate the
last-resort carbapenems and because MBL inhibitors of clinical value are still
lacking. We previously identified the original binding mode of 4-amino-2,4
dihydro-5-(2-methylphenyl)-3H-1,2,4-triazole-3-thione (compound IIIA) within the
dizinc active site of the L1 MBL. Herein we present the crystallographic
structure of a complex of L1 with the corresponding non-amino compound IIIB (1,2
dihydro-5-(2-methylphenyl)-3H-1,2,4-triazole-3-thione). Unexpectedly, the binding
mode of IIIB was similar but reverse to that of IIIA. The 3 D structures
suggested that the triazole-thione scaffold was suitable to bind to the catalytic
site of dizinc metalloenzymes. On the basis of these results, we synthesized 54
analogues of IIIA or IIIB. Nineteen showed IC50 values in the micromolar range
toward at least one of five representative MBLs (i.e., L1, VIM-4, VIM-2, NDM-1,
and IMP-1). Five of these exhibited a significant inhibition of at least four
enzymes, including NDM-1, VIM-2, and IMP-1. Active compounds mainly featured
either halogen or bulky bicyclic aryl substituents. Finally, some compounds were
also tested on several microbial dinuclear zinc-dependent hydrolases belonging to
the MBL-fold superfamily (i.e., endonucleases and glyoxalase II) to explore their
activity toward structurally similar but functionally distinct enzymes. Whereas
the bacterial tRNases were not inhibited, the best IC50 values toward plasmodial
glyoxalase II were in the 10 MUm range.
PMID- 28505395
TI - Claudin peptidomimetics modulate tissue barriers for enhanced drug delivery.
AB - The blood-brain barrier (BBB) formed by the microvascular endothelium limits
cerebral drug delivery. The paraendothelial cleft is sealed by tight junctions
(TJs) with a major contribution from claudin-5, which we selected as a target to
modulate BBB permeability. For this purpose, drug-enhancer peptides were designed
based on the first extracellular loop (ECL) of claudin-5 to allow transient BBB
permeabilization. Peptidomimetics (C5C2 and derivatives, nanomolar affinity to
claudin-5) size-selectively (<=40 kDa) and reversibly (12-48 h) increased the
permeability of brain endothelial and claudin-5-transfected epithelial cell
monolayers. Upon peptide uptake, the number of TJ strand particles diminished,
claudin-5 was downregulated and redistributed from cell-cell contacts to the
cytosol, and the cell shape was altered. Cellular permeability of doxorubicin
(cytostatic drug, 580 Da) was enhanced after peptide administration. Mouse
studies (3.5 MUmol/kg i.v.) confirmed that, for both C5C2 and a d-amino acid
derivative, brain uptake of Gd-diethylene-triamine penta-acetic acid (547 Da) was
enhanced within 4 h of treatment. On the basis of our functional data, circular
dichroism measurements, molecular modeling, and docking experiments, we suggest
an association model between beta-sheets flanked by alpha-helices, formed by
claudin-5 ECLs, and the peptides. In conclusion, we identified claudin-5
peptidomimetics that improve drug delivery through endothelial and epithelial
barriers expressing claudin-5.
PMID- 28505401
TI - The influence of a composite hospital volume on outcomes for gastric cancer
surgery: A Dutch population-based study.
AB - BACKGROUND: Volume-outcome associations for complex surgical procedures have
motivated centralization of care worldwide. The aim of this study was to
investigate the association between overall hospital experience with complex
upper gastrointestinal (GI) cancer resections and outcomes after gastric cancer
surgery. METHODS: Data on all patients (n = 4837) who underwent a resection for
non metastatic invasive gastric cancer between 2005 and 2014 were obtained from
the Netherlands Cancer Registry (NCR). Annual hospital volume categories were
based on the combined volume of gastrectomies, esophagectomies, and
pancreatectomies (composite hospital volume). Volume-outcome analyses were
performed for lymph node yield, 30-day mortality, and overall survival. RESULTS:
The proportion of gastric cancer resections performed in hospitals with an annual
composite hospital volume of >=40 upper GI cancer resections increased from 6% in
2005 to 80% in 2014. A higher composite hospital volume was univariably
associated with a higher lymph node yield, lower 30-day mortality, and increased
overall survival. Statistical significance was lost after adjusting for case mix.
But, sub group analysis including only elderly patients (>=75 years) showed a
significant association between composite hospital volume and 30-day mortality.
CONCLUSION: In the Netherlands, an increasing proportion of gastric cancer
resections is performed in hospitals with a high composite hospital volume of
gastric, esophageal, and pancreatic cancer resections. Special attention is
warranted to referral of elderly patients, as these patients might specifically
benefit from this centralization.
PMID- 28505403
TI - Prediction of the Wetting Behavior of Active and Hole-Transport Layers for
Printed Flexible Electronic Devices Using Molecular Dynamics Simulations.
AB - Molecular dynamics (MD) simulations were used to predict the wetting behavior of
materials typical of active and hole-transport layers in organic electronics by
evaluating their contact angles and adhesion energies. The active layer (AL) here
consists of a blend of poly(3-hexylthiophene) and phenyl-C61-butyric acid methyl
ester (P3HT:PCBM), whereas the hole-transport layer (HTL) consists of a blend of
poly(3,4-ethylenedioxythiophene) and poly(styrenesulfonate) (PEDOT:PSS).
Simulations of the wetting of these surfaces by multiple solvents show that
formamide, glycerol, and water droplet contact angle trends correlate with
experimental values. However, droplet simulations on surfaces are computationally
expensive and would be impractical for routine use in printed electronics and
other applications. As an alternative, contact angle measurements can be related
to adhesion energy, which can be calculated more quickly and easily from
simulations and has been shown to correlate with contact angles. Calculations of
adhesion energy for 16 different solvents were used to rapidly predict the
wetting behavior of solvents on the AL and HTL surfaces. Among the tested
solvents, pentane and hexane exhibit low and similar adhesion energy on both of
the surfaces considered. This result suggests that among the tested solvents,
pentane and hexane exhibit strong potential as orthogonal solvent in printing
electronic materials onto HTL and AL materials. The simulation results further
show that MD can accelerate the evaluation of processing parameters for printed
electronics.
PMID- 28505402
TI - Influence of Asymmetric Contact Form on Contact Resistance and Schottky Barrier,
and Corresponding Applications of Diode.
AB - We have fabricated carbon nanotube and MoS2 field-effect transistors with
asymmetric contact forms of source-drain electrodes, from which we found the
current directionality of the devices and different contact resistances under the
two current directions. By designing various structures, we can conclude that the
asymmetric electrical performance was caused by the difference in the effective
Schottky barrier height (PhiSB) caused by the different contact forms. A detailed
temperature-dependent study was used to extract and compare the PhiSB for both
contact forms of CNT and MoS2 devices; we found that the PhiSB for the metal-on
semiconductor form was much lower than that of the semiconductor-on-metal form
and is suitable for all p-type, n-type, or ambipolar semiconductors. This
conclusion is meaningful with respect to the design and application of
nanomaterial electronic devices. Additionally, using the difference in barrier
height caused by the contact forms, we have also proposed and fabricated Schottky
barrier diodes with a current ratio up to 104; rectifying circuits consisting of
these diodes were able to work in a wide frequency range. This design avoided the
use of complex chemical doping or heterojunction methods to achieve fundamental
diodes that are relatively simple and use only a single material; these may be
suitable for future application in nanoelectronic radio frequency or integrated
circuits.
PMID- 28505404
TI - Activated Porous Carbon Spheres with Customized Mesopores through Assembly of
Diblock Copolymers for Electrochemical Capacitor.
AB - A series of porous carbon spheres with precisely adjustable mesopores (4-16 nm),
high specific surface area (SSA, ~2000 m2 g-1), and submicrometer particle size
(~300 nm) was synthesized through a facile coassembly of diblock polymer micelles
with a nontoxic dopamine source and a common postactivation process. The mesopore
size can be controlled by the diblock polymer, polystyrene-block-poly(ethylene
oxide) (PS-b-PEO) templates, and has an almost linear dependence on the square
root of the degree of polymerization of the PS blocks. These advantageous
structural properties make the product a promising electrode material for
electrochemical capacitors. The electrochemical capacitive performance was
studied carefully by using symmetrical cells in a typical organic electrolyte of
1 M tetraethylammonium tetrafluoroborate/acetonitrile (TEA BF4/AN) or in an ionic
liquid electrolyte of 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIMBF4),
displaying a high specific capacitance of 111 and 170 F g-1 at 1 A g-1,
respectively. The impacts of pore size distribution on the capacitance
performance were thoroughly investigated. It was revealed that large mesopores
and a relatively low ratio of micropores are ideal for realizing high SSA
normalized capacitance. These results provide us with a simple and reliable way
to screen future porous carbon materials for electrochemical capacitors and
encourage researchers to design porous carbon with high specific surface area,
large mesopores, and a moderate proportion of micropores.
PMID- 28505405
TI - Structural Basis for Xenosiderophore Utilization by the Human Pathogen
Staphylococcus aureus.
AB - Staphylococcus aureus produces a cocktail of metallophores (staphylopine,
staphyloferrin A, and staphyloferrin B) to scavenge transition metals during
infection of a host. In addition, S. aureus displays the extracellular surface
lipoproteins FhuD1 and FhuD2 along with the ABC transporter complex FhuCBG to
facilitate the use of hydroxamate xenosiderophores such as desferrioxamine B
(DFOB) for iron acquisition. DFOB is used as a chelation therapy to treat human
iron overload diseases and has been linked to an increased risk of S. aureus
infections. We used a panel of synthetic DFOB analogs and a FhuD2-selective
trihydroxamate sideromycin to probe xenosiderophore utilization in S. aureus and
establish structure-activity relationships for Fe(III) binding, FhuD2 binding, S.
aureus growth promotion, and competition for S. aureus cell entry. Fe(III)
binding assays and FhuD2 intrinsic fluorescence quenching experiments revealed
that diverse chemical modifications of the terminal ends of linear ferrioxamine
siderophores influences Fe(III) affinity but not FhuD2 binding. Siderophore
sideromycin competition assays and xenosiderophore growth promotion assays
revealed that S. aureus SG511 and ATCC 11632 can distinguish between competing
siderophores based exclusively on net charge of the siderophore-Fe(III) complex.
Our work provides a roadmap for tuning hydroxamate xenosiderophore scaffolds to
suppress (net negative charge) or enhance (net positive or neutral charge) uptake
by S. aureus for applications in metal chelation therapy and siderophore-mediated
antibiotic delivery, respectively.
PMID- 28505406
TI - Electrolyte Volume Effects on Electrochemical Performance and Solid Electrolyte
Interphase in Si-Graphite/NMC Lithium-Ion Pouch Cells.
AB - This study aims to explore the correlations between electrolyte volume,
electrochemical performance, and properties of the solid electrolyte interphase
in pouch cells with Si-graphite composite anodes. The electrolyte is 1.2 M LiPF6
in ethylene carbonate:ethylmethyl carbonate with 10 wt % fluoroethylene
carbonate. Single layer pouch cells (100 mA h) were constructed with 15 wt % Si
graphite/LiNi0.5Mn0.3CO0.2O2 electrodes. It is found that a minimum electrolyte
volume factor of 3.1 times to the total pore volume of cell components (cathode,
anode, and separator) is needed for better cycling stability. Less electrolyte
causes increases in ohmic and charge transfer resistances. Lithium dendrites are
observed when the electrolyte volume factor is low. The resistances from the
anodes become significant as the cells are discharged. Solid electrolyte
interphase thickness grows as the electrolyte volume factor increases and is
nonuniform after cycling.
PMID- 28505408
TI - Ion Mobility, Hydrogen/Deuterium Exchange, and Isotope Scrambling: Tools to Aid
Compound Identification in 'Omics Mixtures.
AB - Liquid chromatography tandem mass spectrometry (LC-MS/MS), a widely used method
for comparative 'omics analysis, experiences challenges with compound
identification due to matrix effects, difficulty in separating isomer and
isobaric ions, and long analysis times. Ion mobility spectrometry (IMS) has
proven to be useful in separating isomer and isobar ions; however, IMS-MS suffers
from decreased peak capacity due to the correlation in ion size and mass. In
proof-of-principle experiments, the use of gas-phase hydrogen/deuterium exchange
(HDX) combined with IMS-MS/MS techniques is demonstrated to offer advantages for
compound identification. Measurements providing unique information for ions
include m/z value, drift time in He buffer gas, drift time in He and D2O buffer
gases, deuterium incorporation pattern (isotopic distribution), deuterium
incorporation pattern after collisional activation, and fragment ion deuterium
incorporation pattern upon collision-induced dissociation (CID). These techniques
are here shown to be highly reproducible (drift time coefficients of variation <
1.0% and isotopic pattern root-mean-square deviations of 0.5-1.5%) while
demonstrating an increased ability to distinguish individual molecules from
diverse classes of compounds (peptides, catecholamines, nucleosides, amino acids,
etc.). The concept of using such (and similar) information for rapid, high
throughput molecular identification via database searching of standard libraries
is briefly discussed, and an example of such usage is presented for a bonafide
metabolite extract sample.
PMID- 28505407
TI - N-Phenylacetylation and Nonribosomal Peptide Synthetases with Substrate
Promiscuity for Biosynthesis of Heptapeptide Variants, JBIR-78 and JBIR-95.
AB - JBIR-78 (1) and JBIR-95 (2), both of which are heptapeptide derivatives isolated
from Kibdelosporangium sp. AK-AA56, have the same amino acid sequences except for
the second amino acid: phenylacetic acid (Paa)-l-Val-d-Asp (1)/d-cysteic acid (2)
l-Ala-(3S)-3-hydroxy-d-Leu-Gly-d-Ala-l-Phe. Heterologous expression of the
biosynthetic gene cluster including genes encoding nonribosomal peptide
synthetases (NRPS) and in vitro assays with recombinant Orf3, an l-cysteic acid
synthase homologue, suggested the single A domain in module 2 activates both l
Asp and l-cysteic acid to yield 1 and 2, respectively, although the substrate
specificities of the A domains of NRPSs are usually strict. Biosynthetic
mechanism of introduction of N-terminal Paa was also investigated. Recombinant
Orf1 and Orf2 similar to subunits of pyruvate dehydrogenase complex catalyzed the
conversion of phenylpyruvate into phenylacetyl-CoA together with dihydrolipoyl
dehydrogenase whose encoding gene is located outside of the gene cluster.
Moreover, we showed that phenylacetyl-CoA was directly condensed with l-Val,
which was tethered to a peptidyl carrier protein, at the first condensation
domain in the NRPS.
PMID- 28505409
TI - Human Asthmatic Bronchial Cells Are More Susceptible to Subchronic Repeated
Exposures of Aerosolized Carbon Nanotubes At Occupationally Relevant Doses Than
Healthy Cells.
AB - Although acute pulmonary toxicity of carbon nanotubes (CNTs) has been extensively
investigated, the knowledge of potential health effects following chronic
occupational exposure is currently limited and based only upon in vivo
approaches. Our aim was to realistically mimic subchronic inhalation of
multiwalled CNTs (MWCNTs) in vitro, using the air-liquid interface cell exposure
(ALICE) system for aerosol exposures on reconstituted human bronchial tissue from
healthy and asthmatic donors. The reliability and sensitivity of the system were
validated using crystalline quartz (DQ12), which elicited an increased (pro
)inflammatory response, as reported in vivo. At the administrated MWCNT doses
relevant to human occupational lifetime exposure (10 MUg/cm2 for 5 weeks of
repeated exposures/5 days per week) elevated cilia beating frequency (in both
epithelial cultures), and mucociliary clearance (in asthmatic cells only)
occurred, whereas no cytotoxic reactions or morphological changes were observed.
However, chronic MWCNT exposure did induce an evident (pro-)inflammatory and
oxidative stress response in both healthy and asthmatic cells. The latter
revealed stronger and more durable long-term effects compared to healthy cells,
indicating that individuals with asthma may be more susceptible to adverse
effects from chronic MWCNT exposure. Our results highlight the power of
occupationally relevant subchronic exposures on human in vitro models in
nanosafety hazard assessment.
PMID- 28505410
TI - New Prodigiosin Derivatives Obtained by Mutasynthesis in Pseudomonas putida.
AB - The deeply red-colored natural compound prodigiosin is a representative of the
prodiginine alkaloid family, which possesses bioactivities as antimicrobial,
antitumor, and antimalarial agents. Various bacteria including the opportunistic
human pathogen Serratia marcescens and different members of the Streptomycetaceae
and Pseudoalteromonadaceae produce prodiginines. In addition, these microbes
generally accumulate many structurally related alkaloids making efficient
prodiginine synthesis and purification difficult and expensive. Furthermore, it
is known that structurally different natural prodiginine variants display
differential bioactivities. In the herein described mutasynthesis approach, 13
different derivatives of prodigiosin were obtained utilizing the GRAS (generally
recognized as safe) classified strain Pseudomonas putida KT2440. Genetic
engineering of the prodigiosin pathway together with incorporation of synthetic
intermediates thus resulted in the formation of a so far unprecedented structural
diversity of new prodiginine derivatives in P. putida. Furthermore, the formed
products allow reliable conclusions regarding the substrate specificity of PigC,
the final condensing enzyme in the prodigiosin biosynthesis pathway of S.
marcescens. The biological activity of prodigiosin toward modulation of autophagy
was preserved in prodiginine derivatives. One prodiginine derivative displayed
more potent autophagy inhibitory activity than the parent compound or the
synthetic clinical candidate obatoclax.
PMID- 28505411
TI - Quantification of Endogenous Cholesterol in Human Serum on Paper Using Direct
Analysis in Real Time Mass Spectrometry.
AB - Blood testing for endogenous small metabolites to determine physiological and
biochemical states is routine for laboratory analysis. Here we demonstrate that
by combining the commercial direct analysis in real time (DART) ion source with
an ion trap mass spectrometer, native cholesterol in its free alcohol form is
readily detected from a few hundred nanoliters of human serum loaded onto
chromatography paper. Deuterium-labeled cholesterol was used as the internal
standard to obtain the absolute quantity of the endogenous cholesterol. The
amount of the cholesterol measured by this paper-loaded DART mass spectrometry
(pDART-MS) is statistically comparable with that obtained by using commercially
available fluorometric-enzymatic assay and liquid chromatography/mass
spectrometry. Furthermore, sera from 21 participants at three different time
points in an ultramarathon were collected to obtain their cholesterol levels. The
test requires only very minimal sample preparation, and the concentrations of
cholesterol in each sample were acquired within a minute.
PMID- 28505412
TI - Diffraction-Free Bloch Surface Waves.
AB - Here, we demonstrate a diffraction-free Bloch surface wave sustained on all
dielectric multilayers that does not diffract after being passed through three
obstacles or across a single mode fiber. It can propagate in a straight line for
distances longer than 110 MUm at a wavelength of 633 nm and could be applied as
an in-plane optical virtual probe both in air and in an aqueous environment. Its
ability to be used in water, its long diffraction-free distance, and its
tolerance to multiple obstacles make this wave ideal for certain applications in
areas such as the biological sciences, where many measurements are made on glass
surfaces or for which an aqueous environment is required, and for high-speed
interconnections between chips, where low loss is necessary.
PMID- 28505414
TI - Quantitative Online Liquid Chromatography-Surface-Enhanced Raman Scattering (LC
SERS) of Methotrexate and its Major Metabolites.
AB - The application of Raman spectroscopy as a detection method coupled with liquid
chromatography (LC) has recently attracted considerable interest, although this
has currently been limited to isocratic elution. The combination of LC with
rapidly advancing Raman techniques, such as surface-enhanced Raman scattering
(SERS), allows for rapid separation, identification and quantification, leading
to quantitative discrimination of closely eluting analytes. This study has
demonstrated the utility of SERS in conjunction with reversed-phase liquid
chromatography (RP-LC), for the detection and quantification of the
therapeutically relevant drug molecule methotrexate (MTX) and its metabolites 7
hydroxy methotrexate (7-OH MTX) and 2,4-diamino-N(10)-methylpteroic acid (DAMPA)
in pure solutions and mixtures, including spikes into human urine from a healthy
individual and patients under medication. While the RP-LC analysis developed
employed gradient elution, where the chemical constituents of the mobile phase
were modified stepwise during analysis, this did not overtly interfere with the
SERS signals. In addition, the practicability and clinical utility of this
approach has also been demonstrated using authentic patients' urine samples.
Here, the identification of MTX, 7-OH MTX and DAMPA are based on their unique
SERS spectra, providing limits of detection of 2.36, 1.84, and 3.26 MUM
respectively. Although these analytes are amenable to LC and LC-MS detection an
additional major benefit of the SERS approach is its applicability toward the
detection of analytes that do not show UV absorption or are not ionised for mass
spectrometry (MS)-based detection. The results of this study clearly demonstrate
the potential application of online LC-SERS analysis for real-time high
throughput detection of drugs and their related metabolites in human biofluids.
PMID- 28505413
TI - Protein Displacement by Herpes Helicase-Primase and the Key Role of UL42 during
Helicase-Coupled DNA Synthesis by the Herpes Polymerase.
AB - The herpes helicase-primase (UL5-UL8-UL52) very inefficiently unwinds double
stranded DNA. To better understand the mechanistic consequences of this
inefficiency, we investigated protein displacement activity by UL5-UL8-UL52, as
well as the impact of coupling DNA synthesis by the herpes polymerase with
helicase activity. While the helicase can displace proteins bound to the lagging
strand template, bound proteins significantly impede helicase activity.
Remarkably, UL5-UL8-UL52, an extremely inefficient helicase, disrupts the
exceptionally tight interaction between streptavidin and biotin on the lagging
strand template. It also unwinds DNA containing streptavidin bound to the leading
strand template, although it does not displace the streptavidin. These data
suggest that the helicase may largely or completely wrap around the lagging
strand template, with minimal interactions with the leading strand template. We
utilized synthetic DNA minicircles to study helicase activity coupled with the
herpes polymerase-processivity factor (UL30-UL42). Coupling greatly enhances
unwinding of DNA, although bound proteins still inhibit helicase activity.
Surprisingly, while UL30-UL42 and two noncognate polymerases (Klenow Fragment and
T4 DNA polymerase) all stimulate unwinding of DNA by the helicase, the isolated
UL30 polymerase (i.e., no UL42 processivity factor) binds to the replication fork
but in a manner that is incompetent in terms of coupled helicase-polymerase
activity.
PMID- 28505415
TI - Surface-Guided Core-Shell ZnSe@ZnTe Nanowires as Radial p-n Heterojunctions with
Photovoltaic Behavior.
AB - The organization of nanowires on surfaces remains a major obstacle toward their
large-scale integration into functional devices. Surface-material interactions
have been used, with different materials and substrates, to guide horizontal
nanowires during their growth into well-organized assemblies, but the only guided
nanowire heterostructures reported so far are axial and not radial. Here, we
demonstrate the guided growth of horizontal core-shell nanowires, specifically of
ZnSe@ZnTe, with control over their crystal phase and crystallographic
orientations. We exploit the directional control of the guided growth for the
parallel production of multiple radial p-n heterojunctions and probe their
optoelectronic properties. The devices exhibit a rectifying behavior with
photovoltaic characteristics upon illumination. Guided nanowire heterostructures
enable the bottom-up assembly of complex semiconductor structures with controlled
electronic and optoelectronic properties.
PMID- 28505416
TI - High-Temperature-Short-Time Annealing Process for High-Performance Large-Area
Perovskite Solar Cells.
AB - Organic-inorganic hybrid metal halide perovskite solar cells (PSCs) are
attracting tremendous research interest due to their high solar-to-electric power
conversion efficiency with a high possibility of cost-effective fabrication and
certified power conversion efficiency now exceeding 22%. Although many effective
methods for their application have been developed over the past decade, their
practical transition to large-size devices has been restricted by difficulties in
achieving high performance. Here we report on the development of a simple and
cost-effective production method with high-temperature and short-time annealing
processing to obtain uniform, smooth, and large-size grain domains of perovskite
films over large areas. With high-temperature short-time annealing at 400
degrees C for 4 s, the perovskite film with an average domain size of 1 MUm was
obtained, which resulted in fast solvent evaporation. Solar cells fabricated
using this processing technique had a maximum power conversion efficiency
exceeding 20% over a 0.1 cm2 active area and 18% over a 1 cm2 active area. We
believe our approach will enable the realization of highly efficient large-area
PCSs for practical development with a very simple and short-time procedure. This
simple method should lead the field toward the fabrication of uniform large-scale
perovskite films, which are necessary for the production of high-efficiency solar
cells that may also be applicable to several other material systems for more
widespread practical deployment.
PMID- 28505417
TI - Hierarchical Chitin Fibers with Aligned Nanofibrillar Architectures: A Nonwoven
Mat Separator for Lithium Metal Batteries.
AB - Here, we introduce regenerated fibers of chitin (Chiber), the second most
abundant biopolymer after cellulose, and propose its utility as a nonwoven fiber
separator for lithium metal batteries (LMBs) that exhibits an excellent
electrolyte-uptaking capability and Li-dendrite-mitigating performance. Chiber is
produced by a centrifugal jet-spinning technique, which allows a simple and fast
production of Chibers consisting of hierarchically aligned self-assembled chitin
nanofibers. Following the scrutinization on the Chiber-Li-ion interaction via
computational methods, we demonstrate the potential of Chiber as a nonwoven mat
type separator by monitoring it in Li-O2 and Na-O2 cells.
PMID- 28505418
TI - How Mutations Can Resist Drug Binding yet Keep HIV-1 Protease Functional.
AB - Human immunodeficiency virus-1 (HIV-1) protease is an important drug target for
acquired immune deficiency syndrome therapy. Nearly 10 small molecule drugs have
been approved by the Food and Drug Administration (FDA). However, prolonged use
of these drugs produced protease mutants that are not susceptible to many of
these drugs. The mutated proteases, however, continue to cleave the substrate
peptides and thus remain largely functional. This poses a major challenge for the
treatment strategies. Thus, it has become imperative to understand how these
mutations induce drug resistance while maintaining the enzymatic activity of this
protein. Here, we perform a comprehensive study of the wild type (WT) and
clinically relevant mutated protease bound to a series of FDA-approved drugs and
substrates of varying sequences to unravel the mechanism of unhindered activity
of the drug-resistant protease variants. Our results from large molecular
dynamics simulations suggest that while binding of the substrate to WT and
protease mutants involves multiple H-bonding interactions between substrate
subsites and the protease's main chain atoms, the drug binds primarily through
the hydrophobic interactions with the side chains of protease's active site and
flap residues. This implies that any side chain variations caused by mutations in
protease could greatly modulate the binding affinity of inhibitors, but not of
the substrates. The significantly weaker free energy of binding of the drugs
could also be attributed to the limited number of interaction subsites present in
the inhibitor structures compared to the substrates. These findings in
combination with the identified protease flap and active site residues that
contribute to ligand recognition and strong binding can help in the design of
future resistance-evading HIV-1 protease inhibitors.
PMID- 28505419
TI - Copper-Zinc-Tin-Sulfide Thin Films via Annealing of Ultrasonic Spray Deposited
Nanocrystal Coatings.
AB - Thin polycrystalline films of the solar absorber copper-zinc-tin-sulfide (CZTS)
were formed by annealing coatings deposited on molybdenum-coated soda lime glass
via ultrasonic spraying of aerosol droplets from colloidal CZTS nanocrystal
dispersions. Production of uniform continuous nanocrystal coatings with
ultrasonic spraying requires that the evaporation time is longer than the aerosol
flight time from the spray nozzle to the substrate such that the aerosol droplets
still have low enough viscosity to smooth the impact craters that form on the
coating surface. In this work, evaporation was slowed by adding a high boiling
point cosolvent, cyclohexanone, to toluene as the dispersing liquid. We analyzed,
quantitatively, the effects of the solvent composition on the aerosol and coating
drying dynamics using an aerosol evaporation model. Annealing coatings in sulfur
vapor converts them into polycrystalline films with micrometer size grains, but
the grains form continuous films only when Na is present during annealing to
enhance grain growth. Continuous films are easier to form when the average
nanocrystal size is 15 nm: using larger nanocrystals (e.g., 20 nm) sacrifices
film continuity.
PMID- 28505420
TI - Immobilization of l-Asparaginase on Carrier Materials: A Comprehensive Review.
AB - There are two major applications of l-asparaginase (L-ASNase): leukemia therapy
and the food industry. Especially, its chemotherapeutic effect has attracted
interest from the scientific community and individual scientists. Therefore, to
protect the intrinsic activity and half-time of L-ASNase, several carriers and
immobilization techniques for immobilization of L-ASNase have been described in
articles. Unfortunately, a comprehensive review about immobilization of L-ASNase
has not been written until now. In this review, we have thoroughly discussed the
carriers for L-ASNase by illustrating immobilization findings including both past
and present applications. In addition, we have revealed advantages and
disadvantages of immobilized enzyme and related it to free form. We believe that
this review will not only provide background information, but also guide future
developments.
PMID- 28505421
TI - Development of High-Performance Chemical Isotope Labeling LC-MS for Profiling the
Carbonyl Submetabolome.
AB - Metabolites containing a carbonyl group represent several important classes of
molecules including various forms of ketones and aldehydes such as steroids and
sugars. We report a high-performance chemical isotope labeling (CIL) LC-MS method
for profiling the carbonyl submetabolome with high coverage and high accuracy and
precision of relative quantification. This method is based on the use of
dansylhydrazine (DnsHz) labeling of carbonyl metabolites to change their chemical
and physical properties to such an extent that the labeled metabolites can be
efficiently separated by reversed phase LC and ionized by electrospray ionization
MS. In the analysis of six standards representing different carbonyl classes,
acetaldehyde could be ionized only after labeling and MS signals were
significantly increased for other 5 standards with an enhancement factor ranging
from ~15-fold for androsterone to ~940-fold for 2-butanone. Differential 12C- and
13C-DnsHz labeling was developed for quantifying metabolic differences in
comparative samples where individual samples were separately labeled with 12C
labeling and spiked with a 13C-labeled pooled sample, followed by LC-MS analysis,
peak pair picking, and peak intensity ratio measurement. In the replicate
analysis of a 1:1 12C-/13C-labeled human urine mixture (n = 6), an average of
2030 +/- 39 pairs per run were detected with 1737 pairs in common, indicating the
possibility of detecting a large number of carbonyl metabolites as well as high
reproducibility of peak pair detection. The average RSD of the peak pair ratios
was 7.6%, and 95.6% of the pairs had a RSD value of less than 20%, demonstrating
high precision for peak ratio measurement. In addition, the ratios of most peak
pairs were close to the expected value of 1.0 (e.g., 95.5% of them had ratios of
between 0.67 and 1.5), showing the high accuracy of the method. For metabolite
identification, a library of DnsHz-labeled standards was constructed, including
78 carbonyl metabolites with each containing MS, retention time (RT), and MS/MS
information. This library and an online search program for labeled carbonyl
metabolite identification based on MS, RT, and MS/MS matches have been
implemented in a freely available Website, www.mycompoundid.org . Using this
library, out of the 1737 peak pairs detected in urine, 33 metabolites were
positively identified. In addition, 1333 peak pairs could be matched to the
metabolome databases with most of them belonging to the carbonyl metabolites.
These results show that 12C-/13C-DnsHz labeling LC-MS is a useful tool for
profiling the carbonyl submetabolome of complex samples with high coverage.
PMID- 28505423
TI - Simple Inkjet Process To Fabricate Microstructures of Chitinous Nanocrystals for
Cell Patterning.
AB - Structural polysaccharide nanocrystals (NCs) including cellulose nanocrystal have
attracted attention. In order to broaden the range of application of the NCs, we
can take advantage of their original characteristics by establishing simple and
reasonable processing methods. We here demonstrate a micropatterning of animal
cellular adhesion by inkjet printing of aqueous dispersions of cytocompatible
chitinous NCs onto cellophane films. We display how to regulate the deposition
form and two-dimensional shape of the chitinous NC micromoldings using a research
inkjet printer. Adhesive capability of mouse fibroblasts onto the chitinous
substrates was greatly improved by alkali deacetylation. The deacetylated
products remained rod-like nanostructures, but the original chitin crystal form
changed to that of chitosan by an intensive deacetylation. The adhered cells
could be recovered glycolytically. The chitinous micropatterning substrates can
be utilized for biomedical applications such as controlling of cellular shapes,
precise monitoring molecular events in biochemistry, and drug screening.
PMID- 28505422
TI - Oxygen Sensing with Perfluorocarbon-Loaded Ultraporous Mesostructured Silica
Nanoparticles.
AB - Oxygen homeostasis is important in the regulation of biological function. Disease
progression can be monitored by measuring oxygen levels, thus producing
information for the design of therapeutic treatments. Noninvasive measurements of
tissue oxygenation require the development of tools with minimal adverse effects
and facile detection of features of interest. Fluorine magnetic resonance imaging
(19F MRI) exploits the intrinsic properties of perfluorocarbon (PFC) liquids for
anatomical imaging, cell tracking, and oxygen sensing. However, the highly
hydrophobic and lipophobic properties of perfluorocarbons require the formation
of emulsions for biological studies, though stabilizing these emulsions has been
challenging. To enhance the stability and biological loading of perfluorocarbons,
one option is to incorporate perfluorocarbon liquids into the internal space of
biocompatible mesoporous silica nanoparticles. Here, we developed perfluorocarbon
loaded ultraporous mesostructured silica nanoparticles (PERFUMNs) as 19F MRI
detectable oxygen-sensing probes. Ultraporous mesostructured silica nanoparticles
(UMNs) have large internal cavities (average = 1.8 cm3 g-1), facilitating an
average 17% loading efficiency of PFCs, meeting the threshold fluorine
concentrations needed for imaging studies. Perfluoro-15-crown-5-ether PERFUMNs
have the highest equivalent nuclei per PFC molecule and a spin-lattice (T1)
relaxation-based oxygen sensitivity of 0.0032 mmHg-1 s-1 at 16.4 T. The option of
loading PFCs after synthesizing UMNs, rather than traditional in situ core-shell
syntheses, allows for use of a broad range of PFC liquids from a single material.
The biocompatible and tunable chemistry of UMNs combined with the intrinsic
properties of PFCs makes PERFUMNs a MRI sensor with potential for anatomical
imaging, cell tracking, and metabolic spectroscopy with improved stability.
PMID- 28505424
TI - Addressing the Issue of Microplastics in the Wake of the Microbead-Free Waters
Act-A New Standard Can Facilitate Improved Policy.
AB - The United States Microbead-Free Waters Act was signed into law in December 2015.
It is a bipartisan agreement that will eliminate one preventable source of
microplastic pollution in the United States. Still, the bill is criticized for
being too limited in scope, and also for discouraging the development of
biodegradable alternatives that ultimately are needed to solve the bigger issue
of plastics in the environment. Due to a lack of an acknowledged, appropriate
standard for environmentally safe microplastics, the bill banned all plastic
microbeads in selected cosmetic products. Here, we review the history of the
legislation and how it relates to the issue of microplastic pollution in general,
and we suggest a framework for a standard (which we call "Ecocyclable") that
includes relative requirements related to toxicity, bioaccumulation, and
degradation/assimilation into the natural carbon cycle. We suggest that such a
standard will facilitate future regulation and legislation to reduce pollution
while also encouraging innovation of sustainable technologies.
PMID- 28505425
TI - Refined Crystal Structure of Samia cynthia ricini Silk Fibroin Revealed by Solid
State NMR Investigations.
AB - Samia cynthia ricini is one of the wild silkworms and its silk fibroin (SF)
consists of alternatively repeating poly-l-alanine (PLA) sequences as crystalline
domain and glycine-rich sequences as noncrystalline domain; the structure is
similar to those of spider silk and other wild silkworm silks. In this paper, we
proposed a new staggered model for the packing arrangement of the PLA sequence
through the use of the Cambridge Serial Total Energy Package program and a
comparison of the observed and calculated chemical shifts of the PLA sequence
with the Gauge Including Projector Augmented Wave method. The new model was
supported by the interatomic distance information from the cross peaks of Ala
Cbeta dipolar-assisted rotational resonance (DARR) spectrum of the PLA sequences
in S. c. ricini SF fiber. In addition, three 13C NMR peaks observed in the beta
sheet region were assigned to the carbons with different environments in the same
model, but not assigned to different beta-sheet structures.
PMID- 28505426
TI - Tuning the Shell Number of Multishelled Metal Oxide Hollow Fibers for Optimized
Lithium-Ion Storage.
AB - Searching the long-life transition-metal oxide (TMO)-based materials for future
lithium-ion batteries (LIBs) is still a great challenge because of the mechanical
strain resulting from volume change of TMO anodes during the
lithiation/delithiation process. To well address this challenging issue, we
demonstrate a controlled method for making the multishelled TMO hollow
microfibers with tunable shell numbers to achieve the optimal void for efficient
lithium-ion storage. Such a particularly designed void can lead to a short
diffusion distance for fast diffusion of Li+ ions and also withstand a large
volume variation upon cycling, both of which are the key for high-performance
LIBs. Triple-shelled TMO hollow microfibers are a quite stable anode material for
LIBs with high reversible capacities (NiO: 698.1 mA h g-1 at 1 A g-1; Co3O4:
940.2 mA h g-1 at 1 A g-1; Fe2O3: 997.8 mA h g-1 at 1 A g-1), excellent rate
capability, and stability. The present work opens a way for rational design of
the void of multiple shells in achieving the stable lithium-ion storage through
the biomass conversion strategy.
PMID- 28505427
TI - Modification of Sialic Acids on Solid Phase: Accurate Characterization of Protein
Sialylation.
AB - Sialic acids play many important roles in several physiological and pathological
processes, including cancers, infection, and blood diseases. Sialic acids are
fragile and prone to fragmentation under electrospray ionization and matrix
assisted laser desorption/ionization. It is crucial to modify sialic acids for
qualitative and quantitative identification of their change in abundance in
complex biological samples. Permethylation is a method of choice for sialic acid
stabilization, but the harsh conditions during permethylation may lead to the
decomposition of O-acetyl groups. Esterification or amidation in solution
effectively protects sialic acids, yet it is not trivial to purify glycans from
their reagents. Quantitative analysis of glycans can be achieved by labeling
their reducing end using fluorescent tags. Loss of sialic acids during labeling
is a major concern. In this study, we demonstrated the utility of sialic acids
modification for the analysis of sialyl oligosaccharides and glycopeptides.
Without modification, sialic acids are partially or completely lost during sample
preparation, leading to the presence of false glycans or glycopeptides in the
sample. The stabilized sialic acids not only result in accurate identification of
sialylated glycans but also improve the characterization of intact glycopeptides.
The modification of sialic acids on the solid support facilitates analysis of
glycans and their intact glycoproteins.
PMID- 28505428
TI - Toggling of Diacylglycerol Affinity Correlates with Conformational Plasticity in
C1 Domains.
AB - Conserved homology-1 (C1) domains are peripheral membrane domains that target
their host proteins to diacylglycerol (DAG)-containing membranes. It has been
previously shown that a conservative aromatic mutation of a single residue in the
C1 domain has a profound effect on DAG affinity. We report that the "DAG
toggling" mutation changes the conformational dynamics of the loop region that
forms the binding site for the C1 activators. Moreover, there is a correlation
among the residue identity at the mutation site, DAG affinity, and loop dynamics
in four C1 variants. We propose that "toggling" of DAG affinity may occur through
modulation of both protein-membrane interactions and the geometry of the
activator-binding cleft, with the loop dynamics being responsible for the latter.
PMID- 28505431
TI - Stepping Library-Based Post-SELEX Strategy Approaching to the Minimized Aptamer
in SPR.
AB - When evolved from SELEX (systematic evolution of ligands by exponential
enrichment), aptamers are generally about 70-130 nucleotides in length and needed
to be effectively truncated for further diagnosis or therapeutic uses. Post-SELEX
optimization is then aroused to simplify the aptamer sequence and improve the
affinity property. In this work, we report a new post-SELEX strategy based on a
stepping library for the first time. With a hypothesis that one nucleobase can
influence the whole binding affinity through its adjacent base stacking and
potential steric hydrogen bonding interaction, we designed a stepping library
composed of all probable nucleotide truncation directions. We employed an aptamer
807-39nt toward EPO-alpha as a model, and surface plasmon resonance (SPR) as an
efficient screening and evaluation method to optimize all label-free sequences in
the library. We have successfully picked out In27 as the minimized aptamer from a
mini library of only 35 sequences. Aptamer In27 has a sole loop, without the
original stem portion of the initial aptamer, but retains the whole binding
affinity. We have also defined the key nucleotide contribution by site
mutagenesis with natural bases, and finally produced a degenerated sequence with
higher or the same good affinities. Furthermore, we explored different binding
behaviors between aptamer In27 and other recognition molecule such as agglutinin,
monoclonal antibody, or receptor by competition or binding assays. Our work
provides a new and efficient post-SELEX optimization strategy, as well as a
minimized aptamer In27 with an explicit degenerated sequence and a defined
binding behavior. That would enhance their great potential in future diagnosis
and therapy.
PMID- 28505430
TI - Proteins and Amino Acids in Fine Particulate Matter in Rural Guangzhou, Southern
China: Seasonal Cycles, Sources, and Atmospheric Processes.
AB - Water-soluble proteinaceous matter including proteins and free amino acids (FAAs)
as well as some other chemical components was analyzed in fine particulate matter
(PM2.5) samples collected over a period of one year in rural Guangzhou. Annual
averaged protein and total FAAs concentrations were 0.79 +/- 0.47 MUg m-3 and
0.13 +/- 0.05 MUg m-3, accounting for 1.9 +/- 0.7% and 0.3 +/- 0.1% of PM2.5,
respectively. Among FAAs, glycine was the most abundant species (19.9%), followed
by valine (18.5%), methionine (16.1%), and phenylalanine (13.5%). Both proteins
and FAAs exhibited distinct seasonal variations with higher concentrations in
autumn and winter than those in spring and summer. Correlation analysis suggests
that aerosol proteinaceous matter was mainly derived from intensive agricultural
activities, biomass burning, and fugitive dust/soil resuspension. Significant
correlations between proteins/FAAs and atmospheric oxidant (O3) indicate that
proteins/FAAs may be involved in O3 related atmospheric processes. Our
observation confirms that ambient FAAs could be degraded from proteins under the
influence of O3, and the stoichiometric coefficients of the reactions were
estimated for FAAs and glycine. This finding provides a possible pathway for the
production of aerosol FAAs in the atmosphere, which will improve the current
understanding on atmospheric processes of proteinaceous matter.
PMID- 28505429
TI - Control of the Yeast Mating Pathway by Reconstitution of Functional alpha-Factor
Using Split Intein-Catalyzed Reactions.
AB - Synthetic control strategies using signaling peptides to regulate and coordinate
cellular behaviors in multicellular organisms and synthetic consortia remain
largely underdeveloped because of the complexities necessitated by heterologous
peptide expression. Using recombinant proteins that exploit split intein-mediated
reactions, we presented here a new strategy for reconstituting functional
signaling peptides capable of eliciting desired cellular responses in S.
cerevisiae. These designs can potentially be tailored to any signaling peptides
to be reconstituted, as the split inteins are promiscuous and both the peptides
and the reactions are amenable to changes by directed evolution and other protein
engineering tools, thereby offering a general strategy to implement synthetic
control strategies in a large variety of applications.
PMID- 28505432
TI - Development of a New Extraction Device Based on Parallel-Electromembrane
Extraction.
AB - A new device for parallel-electromembrane extraction (Pa-EME) was developed to
enable simultaneous and high-throughput extraction of ionic and ionizable
compounds from biofluids. The new system is composed of a reusable conductive
well-plate used as an acceptor compartment and a filtration well-plate used as a
donor compartment. A design of experiments was implemented to optimize the main
experimental parameters (agitation, voltage, and time) with standard solutions in
formic acid 50 mM. The stirring rate was found the primary influent parameter.
The Pa-EME device showed excellent extraction yields from 84% to 101% with RSD
lower than 7.5% on model compounds. Optimized parameters were then applied to
plasma samples and process efficiencies from 59% to 62% and RSD of less than 8.0%
were obtained. The whole extraction process took less than 20 min to prepare 8
samples simultaneously, greatly enhancing the sample preparation throughput (<3
min per sample).
PMID- 28505433
TI - Do Environmental Fluoride Exposure and ESRalpha Genetic Variation Modulate
Methylation Modification on Bone Changes in Chinese Farmers?
AB - Although increasing evidence suggests that estrogen receptor alpha (ESRalpha)
genetic variation could modify bone damage caused by environmental fluoride
exposure, little is known about epigenetic mechanisms in relation to bone
changes. A case-control study was conducted among farmers aged 18-55 years in
Henan Province, China. X-ray was used to detect bone changes. Methylation status
was determined by methylation-specific PCR. Genotypes were identified by Taqman
probe and real-time PCR. In this study, we found that methylation status in the
promoter region of the ESRalpha gene was lower in bone change cases than that in
controls, which was only observed in male farmers after stratification by gender.
Furthermore, methylation level was negatively associated with the urinary
fluoride concentration in male farmers. No significant association was found
between the distribution of ESRalpha rs2941740 genotypes and the risk of bone
changes. Multivariate logistic regression analysis showed that after adjusting
for age and gender, increased serum calcium and methylation status were
protective factors for bone changes. No interaction effect was observed between
fluoride exposure and ESRalpha rs2941740 polymorphism on bone changes. In
conclusion, the current work suggests that bone changes are associated with
methylation status, which might be modulated by fluoride exposure in male
farmers. Methylation status and bone changes were not modified by ESRalpha gene
rs2941740 polymorphism in the promoter region.
PMID- 28505434
TI - Photolysis of Particulate Nitrate as a Source of HONO and NOx.
AB - Photolysis of nitric acid on the surface has been found recently to be greatly
enhanced from that in the gas phase. Yet, photolysis of particulate nitrate
(pNO3) associated with atmospheric aerosols is still relatively unknown. Here,
aerosol filter samples were collected both near the ground surface and throughout
the troposphere on board the NSF/NACR C-130 aircraft. The photolysis rate
constants of pNO3 were determined from these samples by directly monitoring the
production rates of nitrous acid (HONO) and nitrogen dioxide (NO2) under UV light
(>290 nm) irradiation. Scaled to the tropical noontime condition on the ground
level (solar zenith angle = 0 degrees ), the normalized photolysis rate constants
(jpNO3N) are in the range from 6.2 * 10-6 s-1 to 5.0 * 10-4 s-1 with a median of
8.3 * 10-5 s-1 and a mean (+/-1 SD) of (1.3 +/- 1.2) * 10-4 s-1. Chemical
compositions, specifically nitrate loading and organic matter, affect the rate of
photolysis. Extrapolated to ambient pNO3 loading conditions, e.g. <= 10 nmol m-3,
the mean jpNO3N value is over 1.8 * 10-4 s-1 in the suburban, rural, and remote
environments. Photolysis of particulate nitrate is thus a source of HONO and NO2
in the troposphere.
PMID- 28505436
TI - Control of Heme Coordination and Catalytic Activity by Conformational Changes in
Peptide-Amphiphile Assemblies.
AB - Self-assembling peptide materials have gained significant attention, due to well
demonstrated applications, but they are functionally underutilized. To advance
their utility, we use noncovalent interactions to incorporate the biological
cofactor heme-B for catalysis. Heme-proteins achieve differing functions through
structural and coordinative variations. Here, we replicate this phenomenon by
highlighting changes in heme reactivity as a function of coordination, sequence,
and morphology (micelles versus fibers) in a series of simple peptide amphiphiles
with the sequence c16-xyL3K3-CO2H where c16 is a palmitoyl moiety and xy
represents the heme binding region: AA, AH, HH, and MH. The morphology of this
peptide series is characterized using transmission electron and atomic force
microscopies as well as dynamic light scattering. Within this small library of
peptide constructs, we show that three spectroscopically (UV/visible and electron
paramagnetic resonance) distinct heme environments were generated:
noncoordinated/embedded high-spin, five-coordinate high-spin, and six-coordinate
low-spin. The resulting material's functional dependence on sequence and
supramolecular morphology is highlighted 2-fold. First, the heme active site
binds carbon monoxide in both micelles and fibers, demonstrating that the heme
active site in both morphologies is accessible to small molecules for catalysis.
Second, peroxidase activity was observed in heme-containing micelles yet was
significantly reduced in heme-containing fibers. We briefly discuss the
implications these findings have in the production of functional, self-assembling
peptide materials.
PMID- 28505437
TI - Heteroaggregation of Graphene Oxide with Nanometer- and Micrometer-Sized Hematite
Colloids: Influence on Nanohybrid Aggregation and Microparticle Sedimentation.
AB - Heteroaggregation of graphene oxide (GO) with nanometer- and micrometer-sized
hematite colloids, which are naturally present in aquatic systems, is
investigated in this study. The heteroaggregation rates between GO and hematite
nanoparticles (HemNPs) were quantified by dynamic light scattering, while the
heteroaggregation between GO and micrometer-sized hematite particles (HemMPs) was
examined through batch adsorption and sedimentation experiments. The
heteroaggregation rates of GO with HemNPs first increased and then decreased with
increasing GO/HemNP mass concentration ratios. The conformation of GO-HemNP
heteroaggregates at different GO/HemNP mass concentration ratios was observed
through transmission electron microscopy imaging. Initially, GO underwent
heteroaggregation with HemNPs through electrostatic attraction to form primary
heteroaggregates, which were further bridged by GO to form bigger clusters. At
high GO/HemNP mass concentration ratios where GO outnumbered HemNPs,
heteroaggregation resulted in the formation of stable GO-HemNP nanohybrids that
have a critical coagulation concentration of 308 mM NaCl at pH 5.2. In the case
of HemMPs, GO adsorbed readily on the microparticles and, at an optimal GO/HemMP
ratio of ~0.002, the sedimentation of HemMPs was the fastest, most likely because
of the formation of "electrostatic patches" leading to favorable aggregation of
the microparticles.
PMID- 28505438
TI - pH-Responsive Coassembly of Oligo(ethylene glycol)-Coated Gold Nanoparticles with
External Anionic Polymers via Hydrogen Bonding.
AB - Stimuli-responsive assembly of gold nanoparticles (AuNPs) with precise control of
the plasmonic properties, assembly size, and stimuli responsivity has shown
potential benefits with regard to biosensing devices and drug-delivery systems.
Here we present a new pH-responsive coassembly system of oligo(ethylene glycol)
(OEG)-coated AuNPs with anionic polymers as an external mediator via hydrogen
bonding in water. Hydrogen-bond-driven coassemblies of OEG-AuNPs with
poly(acrylic acid) (PAA) were confirmed by the monitoring of plasmonic peaks and
hydrodynamic diameters. In this system, the protonation of anionic polymers on
change in pH triggered the formation of hydrogen bond between the OEG-AuNPs and
polymers, providing sensitive pH responsivity. The plasmonic properties and
assembly size are affected by both the ratio of PAA to AuNPs and the molecular
weight of PAAs. In addition, the attachment of hydrophobic groups to the surface
ligand or anionic polymer changed the responsive pH range. These results
demonstrated that the coassembly with an external mediator via hydrogen bonding
provides a stimuli-responsive assembly system with tunable plasmonic properties,
assembly size, and stimuli responsivity.
PMID- 28505439
TI - Anthropogenic 236U in Danish Seawater: Global Fallout versus Reprocessing
Discharge.
AB - This work focuses on the occurrence of 236U in seawater along Danish coasts,
which is the sole water-exchange region between the North Sea-Atlantic Ocean and
the Baltic Sea. Seawater collected in 2013 and 2014 were analyzed for 236U (as
well as 238U and 137Cs). Our results indicate that 236U concentrations in Danish
seawater are distributed within a relatively narrow range of (3.6-8.2) * 107
atom/L and, to a certain extent, independent of salinity. 236U/238U atomic ratios
in Danish seawater are more than 4 times higher than the estimated global fallout
value of 1* 10-9. The levels of 236U/238U atomic ratios obtained are comparable
to those reported for the open North Sea and much higher than several other open
oceans worldwide. This indicates that besides the global fallout input, the
discharges from the two major European nuclear reprocessing plants are dominating
sources of 236U in Danish seawater. However, unexpectedly high 236U/238U ratios
as well as high 236U concentrations were observed at low-salinity locations of
the Baltic Sea. While this feature might be interpreted as a clue for another
significant 236U input in the Baltic Sea, it may also be caused by the complexity
of water currents or slow turnover rate.
PMID- 28505440
TI - Iterative Reconstruction of Memory Kernels.
AB - In recent years, it has become increasingly popular to construct coarse-grained
models with non-Markovian dynamics to account for an incomplete separation of
time scales. One challenge of a systematic coarse-graining procedure is the
extraction of the dynamical properties, namely, the memory kernel, from
equilibrium all-atom simulations. In this article, we propose an iterative method
for memory reconstruction from dynamical correlation functions. Compared to
previously proposed noniterative techniques, it ensures by construction that the
target correlation functions of the original fine-grained systems are reproduced
accurately by the coarse-grained system, regardless of time step and
discretization effects. Furthermore, we also propose a new numerical integrator
for generalized Langevin equations that is significantly more accurate than the
more commonly used generalization of the velocity Verlet integrator. We
demonstrate the performance of the above-described methods using the example of
backflow-induced memory in the Brownian diffusion of a single colloid. For this
system, we are able to reconstruct realistic coarse-grained dynamics with time
steps about 200 times larger than those used in the original molecular dynamics
simulations.
PMID- 28505435
TI - Fine-Tuning Strain and Electronic Activation of Strain-Promoted 1,3-Dipolar
Cycloadditions with Endocyclic Sulfamates in SNO-OCTs.
AB - The ability to achieve predictable control over the polarization of strained
cycloalkynes can influence their behavior in subsequent reactions, providing
opportunities to increase both rate and chemoselectivity. A series of new
heterocyclic strained cyclooctynes containing a sulfamate backbone (SNO-OCTs)
were prepared under mild conditions by employing ring expansions of silylated
methyleneaziridines. SNO-OCT derivative 8 outpaced even a difluorinated
cyclooctyne in a 1,3-dipolar cycloaddition with benzylazide. The various orbital
interactions of the propargylic and homopropargylic heteroatoms in SNO-OCT were
explored both experimentally and computationally. The inclusion of these
heteroatoms had a positive impact on stability and reactivity, where electronic
effects could be utilized to relieve ring strain. The choice of the heteroatom
combinations in various SNO-OCTs significantly affected the alkyne geometries,
thus illustrating a new strategy for modulating strain via remote substituents.
Additionally, this unique heteroatom activation was capable of accelerating the
rate of reaction of SNO-OCT with diazoacetamide over azidoacetamide, opening the
possibility of further method development in the context of chemoselective,
bioorthogonal labeling.
PMID- 28505441
TI - Confined Pool-Buried Water-Soluble Nanoparticles from Reverse Micelles.
AB - With the special nature of confined water pools, reverse micelles (RMs) have
shown potential for a wide range of applications. However, the inherent water
insolubility of RMs hinders their further application prospect especially for
applications related to biology. We present herein the first successful
transformation of water-insoluble RMs into water-soluble nanoparticles without
changing the confined aqueous interiors by hydrolysis/aminolysis of arm-cleavable
interfacial cross-linked reverse micelles formed from diester surfactant 1. The
unique properties exhibited by the aqueous interiors of the resulting pool-buried
water-soluble nanoparticles (PWNPs) were demonstrated both by the template
synthesis of gold nanoparticles in the absence of external reductants and by the
fluorescence enhancement of encapsulated thioflavin T (ThT). Importantly, the
unique potential for PWNPs in biological applications was exemplified by the use
of ThT@PWNPs and "cell targeted" ThT@PWNPs as effective optical imaging agents of
living cells. This work conceptually overcomes the application bottleneck of RMs
and opens an entry to a new class of functional materials.
PMID- 28505442
TI - Nitric Oxide Donor-Based Cancer Therapy: Advances and Prospects.
AB - The increasing understanding of the role of nitric oxide (NO) in cancer biology
has generated significant progress in the use of NO donor-based therapy to fight
cancer. These advances strongly suggest the potential adoption of NO donor-based
therapy in clinical practice, and this has been supported by several clinical
studies in the past decade. In this review, we first highlight several types of
important NO donors, including recently developed NO donors bearing a
dinitroazetidine skeleton, represented by RRx-001, with potential utility in
cancer therapy. Special emphasis is then given to the combination of NO donor(s)
with other therapies to achieve synergy and to the hybridization of NO donor(s)
with an anticancer drug/agent/fragment to enhance the activity or specificity or
to reduce toxicity. In addition, we briefly describe inducible NO synthase gene
therapy and nanotechnology, which have recently entered the field of NO donor
therapy.
PMID- 28505444
TI - Explicit Incorporation of Hard and Soft Protein-Protein Interactions into Models
for Crowding Effects in Protein Mixtures. 2. Effects of Varying Hard and Soft
Interactions upon Prototypical Chemical Equilibria.
AB - Previously derived approximate analytical relations for the activity coefficient
of each solute in a mixture of up to three spherical solutes in a highly nonideal
solution interacting via square well potentials of mean force (Hoppe, T.; Minton,
A. P. J Phys Chem B. 2016, 120, 11866-11872) were used to explore the effect of
heterogeneity in volume occupancy and intermolecular interactions upon
prototypical schemes representing solubility, partitioning, conformational
isomerization, and self-association in crowded solutions. Results generally
indicate that all of the equilibria explored are exquisitely sensitive to
variations in both volume occupancy and intermolecular interaction and have
important implications for the design and execution of more detailed simulations
of complex media.
PMID- 28505443
TI - Defect Antiperovskite Compounds Hg3Q2I2 (Q = S, Se, and Te) for Room-Temperature
Hard Radiation Detection.
AB - The high Z chalcohalides Hg3Q2I2 (Q = S, Se, and Te) can be regarded as of
antiperovskite structure with ordered vacancies and are demonstrated to be very
promising candidates for X- and gamma-ray semiconductor detectors. Depending on
Q, the ordering of the Hg vacancies in these defect antiperovskites varies and
yields a rich family of distinct crystal structures ranging from zero-dimensional
to three-dimensional, with a dramatic effect on the properties of each compound.
All three Hg3Q2I2 compounds show very suitable optical, electrical, and good
mechanical properties required for radiation detection at room temperature. These
compounds possess a high density (>7 g/cm3) and wide bandgaps (>1.9 eV), showing
great stopping power for hard radiation and high intrinsic electrical
resistivity, over 1011 Omega cm. Large single crystals are grown using the vapor
transport method, and each material shows excellent photo sensitivity under
energetic photons. Detectors made from thin Hg3Q2I2 crystals show reasonable
response under a series of radiation sources, including 241Am and 57Co radiation.
The dimensionality of Hg-Q motifs (in terms of ordering patterns of Hg vacancies)
has a strong influence on the conduction band structure, which gives the quasi
one-dimensional Hg3Se2I2 a more prominently dispersive conduction band structure
and leads to a low electron effective mass (0.20 m0). For Hg3Se2I2 detectors,
spectroscopic resolution is achieved for both 241Am alpha particles (5.49 MeV)
and 241Am gamma-rays (59.5 keV), with full widths at half-maximum (FWHM, in
percentage) of 19% and 50%, respectively. The carrier mobility-lifetime MUtau
product for Hg3Q2I2 detectors is achieved as 10-5-10-6 cm2/V. The electron
mobility for Hg3Se2I2 is estimated as 104 +/- 12 cm2/(V.s). On the basis of these
results, Hg3Se2I2 is the most promising for room-temperature radiation detection.
PMID- 28505445
TI - Confining Potential as a Function of Polymer Stiffness and Concentration in
Entangled Polymer Solutions.
AB - We directly track the tubelike motion of individual fluorescently labeled polymer
molecules in a concentrated solution of unlabeled polymers. We use a single
molecule wide-field fluorescence microscopy technique that is able to determine
characteristic properties of the polymer dynamics, such as the confining
potential, the tube diameter, and the Rouse time. The use of synthetic polymers
allows us to investigate the confined motion of the polymer chains not only as a
function of polymer concentration (mesh size) but also versus the persistence
length of the matrix polymers. Although the polymers used have a persistence
length much smaller than their contour length, our experimental results lead to a
dependence of the tube diameter on both the mesh size and the persistence length,
which follows the theoretically predicted relation for semiflexible chains.
PMID- 28505446
TI - Role of the C(2)-H Hydrogen Bond Donor in Gas-Phase Microsolvation of Imidazole
Derivatives with ROH (R = CH3, C2H5).
AB - Although the hydrogen-bonding properties of the protic solvents are comparable, a
comparison of the gas-phase structures of water with those of the alcohols
reveals certain similarities as well as differences. In this work we report the
microsolvated clusters of imidazole derivatives, Benzimidazole (BIM) and N
methylbenzimidazole (MBIM) by methanol (M) and ethanol (E) in supersonic jet
using electronic and vibrational spectroscopy and compare them with their
hydrated clusters. The cluster sizes up to 1:2 of BIM/MBIM with methanol and
ethanol, and up to 1:3 in the case of MBIM-methanol were observed. Both the N
H...O and O-H...N bound structures were observed for the BIM-M1 and BIM-E1
complexes. The O-H...N bound structures of 1:1 complexes of MBIM were relatively
more stable than their BIM counterparts by about ~0.25 kcal mol-1. Three distinct
conformations (anti, gauche, and gauche') were identified for the O-H...N bound
complexes of BIM-E1 and MBIM-E1. IR spectroscopy of the doubly and triply
solvated clusters (namely BIM-M2, MBIM-M2,3 and MBIM-E2) gives unequivocal proof
of H-bonded bridges that originate from the N acceptor and terminate at the C(2)
H group, similar to the analogous water clusters. These studies confirm that the
C(2)-H in imidazole plays an important role in its solvation, particularly in the
case of polar solvents. Quantum chemical calculations performed at the DFT (B3LYP
as well as dispersion-corrected functionals) and MP2 levels corroborate the
experimental findings. Comparison of the QTAIM and NBO parameters for the
pairwise solvent interactions in the clusters with those of methanol and ethanol
homodimers reflects the co-operative nature of these H-bonding interactions.
PMID- 28505447
TI - Interrogating the Roles of Post-Translational Modifications of Non-Histone
Proteins.
AB - Post-translational modifications (PTMs) allot versatility to the biological
functions of highly conserved proteins. Recently, modifications to non-histone
proteins such as methylation, acetylation, phosphorylation, glycosylation,
ubiquitination, and many more have been linked to the regulation of pivotal
pathways related to cellular response and stability. Due to the roles these
dynamic modifications assume, their dysregulation has been associated with cancer
and many other important diseases such as inflammatory disorders and
neurodegenerative diseases. For this reason, we present a review and perspective
on important post-translational modifications on non-histone proteins, with
emphasis on their roles in diseases and small molecule inhibitors developed to
target PTM writers. Certain PTMs' contribution to epigenetics has been
extensively expounded; yet more efforts will be needed to systematically dissect
their roles on non-histone proteins, especially for their relationships with
nononcological diseases. Finally, current research approaches for PTM study will
be discussed and compared, including limitations and possible improvements.
PMID- 28505448
TI - Spectroscopic and Calorimetric Studies of Molecular Recognitions in a Dendrimer
Surfactant Complex.
AB - Molecular recognitions, causing supramolecular complex formation between a
hyperbranched polymer molecule (polyamidoamine (PAMAM) dendrimer generation 3)
with oppositely charged surfactant sodium dodecyl sulfate (SDS) in aqueous
solution, were studied by using various spectroscopic techniques and calorimetric
titration of heat change measurements. Spectroscopic measurements were performed
using dynamic Stokes shift (DSS), rotational anisotropy decay, and translational
diffusion of a fluorescent probe molecule coumarin 153 (C153) noncovalently
attached to the dendrimer-surfactant complex. All these studies unanimously
confirm that the critical aggregation concentration (CAC) of SDS falls to ~0.8 mM
(from its critical micelle concentration (CMC) ~ 8 mM) in the presence of ~0.2 mM
dendrimer. Further studies of isothermal titration calorimetry (ITC) measurement
show that the CAC of SDS in the presence of dendrimer remains invariant to the
dendrimer concentration. Complexation reaction between SDS and dendrimer is
highly exothermic in nature. A maximum heat release (DeltaH~ -6.6 kJ/mol of SDS
binding) was observed at a SDS-to-dendrimer mole ratio of ~3-5; where up to 3 to
5 SDS molecules were encapsulated by one dendrimer molecule to form dendrimer-SDS
encapsulation complex. When negatively charged SDS was replaced with a positively
charged surfactant dodecyl-trimethylammonium-bromide (DTAB), we found that the
DTAB hardly interacted with positively charged dendrimer due to the charge-charge
repulsions.
PMID- 28505449
TI - Interfacial Water Arrangement in the Ice-Bound State of an Antifreeze Protein: A
Molecular Dynamics Simulation Study.
AB - Molecular dynamics (MD) simulations have been carried out to study the
heterogeneous ice nucleation on modeled peptide surfaces. Simulations show that
large peptide surfaces made by TxT (threonine-x-threonine) motifs with the
arrangements of threonine (Thr) residues identical to the periodic arrangements
of waters on either the basal or prism plane of ice are capable of ice
nucleation. Nucleated ice plane is the (0001) basal plane of hexagonal ice (Ih)
or (111) plane of cubic ice (Ic). However, due to predefined simulation cell
dimensions, the ice growth is only observed on the surface where the Thr residues
are arranged like the water arrangement on the basal plane of ice Ih. The gamma
methyl and gamma-hydroxyl groups of Thr residue are necessary for such ice
formation. From this ice nucleation and growth simulation, the interfacial water
arrangement in the ice-bound state of Tenebrio molitor antifreeze protein (TmAFP)
has been determined. The interfacial water arrangement in the ice-bound state of
TmAFP is characterized by five-membered hydrogen bonded rings, where each of the
hydroxyl groups of the Thr residues on the ice-binding surface (IBS) of the
protein is a ring member. It is found that the water arrangement at the protein
ice interface is distorted from that in bulk ice. Our analysis further reveals
that the hydroxyl groups of Thr residues on the IBS of TmAFP form maximum three
hydrogen bonds each with the waters in the bound state and methyl groups of Thr
residues occupy wider spaces than the normal grooves on the (111) plane of ice
Ic. Methyl groups are also located above and along the 3-fold rotational axes of
the chair-formed hexagonal hydrogen bonded water rings on the (111) plane.
PMID- 28505450
TI - Asymmetric Spreading of a Drop upon Impact onto a Surface.
AB - Study of the spreading of an impacting drop onto a surface has gained importance
recently due to applications in printing, coating, and icing. Limited studies are
conducted to understand asymmetric spreading of a drop seen upon drop impact onto
a moving surface; there is no relation to describe such spreading. Here, we
experimentally studied the spreading of a drop over a moving surface; such study
also provides insights for systems where a drop impacts at an angle relative to a
surface, i.e., drop has both normal and tangential velocities relative to the
surface. We developed a model that for the first time allows prediction of time
evolution for the asymmetric shape of the lamella during spreading. The developed
model is demonstrated to be valid for a range of liquids and surface
wettabilities as well as drop and surface velocities, making this study a
comprehensive examination of the topic. We also found out how surface wettability
can affect the recoil of the drop after spreading and explained the role of
contact angle hysteresis and receding contact angle in delaying the recoil
process.
PMID- 28505451
TI - Toward Successful Cyclodextrin Based Solubility-Enabling Formulations for Oral
Delivery of Lipophilic Drugs: Solubility-Permeability Trade-Off, Biorelevant
Dissolution, and the Unstirred Water Layer.
AB - The purpose of this work was to investigate key factors dictating the
success/failure of cyclodextrin-based solubility-enabling formulations for oral
delivery of low-solubility drugs. We have studied the solubility, the
permeability, and the solubility-permeability interplay, of the highly lipophilic
drug danazol, formulated with different levels (8.5, 10, 20, and 30%) of the
commonly used hydroxypropyl-beta-cyclodextrin (HPbetaCD), accounting for the
biorelevant solubilization of the drug along the gastrointestinal tract (GIT),
the unstirred water layer (UWL) adjacent to the GI membrane, and the overall
absorption. HPbetaCD significantly increased danazol solubility, and decreased
the drugs' permeability, in a concentration-dependent manner. These Peff results
were in good correlation (R2 = 0.977) to literature rat AUC data of the same
formulations. Unlike vehicle without HPbetaCD, formulations containing 8.5%
HPbetaCD and above were shown to successfully dissolve the drug dose during the
entire biorelevant dissolution experiment. We conclude that CD-based solubility
enabling formulations should contain the minimal amount of CD sufficient to
dissolve the drug dose throughout the GIT, and not more than that; excess CD does
not provide solubility gain but causes further permeability loss, and the overall
absorption is then impaired. Moreover, a significant UWL effect was revealed in
danazol intestinal permeability, and accounting for this effect allowed an
excellent prediction of the solubility-permeability trade-off vs % HPbetaCD.
Overall, this work assessed the contribution of each individual step of the
absorption cascade to the success/failure of HPbetaCD-based formulation, allowing
a more mechanistic development process of better solubility-enabling
formulations.
PMID- 28505452
TI - Deposition Patterns of Two Neighboring Droplets: Onsager Variational Principle
Studies.
AB - When two droplets containing nonvolatile components are sitting close to each
other, asymmetrical ring-like deposition patterns are formed on the substrate. We
propose a simple theory based on the Onsager variational principle to predict the
deposition patterns of two neighboring droplets. The contact line motion and the
interference effect of two droplets are considered simultaneously. We demonstrate
that the gradients of evaporation rate along two droplets is the main reason for
forming asymmetrical deposition patterns. By tracing the relative motion between
the contact line and the solute particles, we found that the velocities of solute
particles have no cylindrical symmetry anymore because of the asymmetrical
evaporation rate, giving the underlying mechanism of forming asymmetrical
patterns. Moreover, controlling the evaporation rate combined with varying the
contact line friction, fan-like and eclipse-like deposition patterns are
obtained. The theoretical results of pinned contact line cases are qualitatively
consistent with the pervious experimental results.
PMID- 28505453
TI - Adaptive and Specific Recognition of Telomeric G-Quadruplexes via Polyvalency
Induced Unstacking of Binding Units.
AB - Targeting DNA G-quadruplexes using small-molecule ligands has shown to modulate
biological functions mediated by G-quadruplexes inside cells. Given >716 000 G
quadruplex hosting sites in human genome, the specific binding of ligands to
quadruplex becomes problematic. Here, we innovated a polyvalency based mechanism
to specifically target multiple telomeric G-quadruplexes. We synthesized a
tetrameric telomestatin derivative and evaluated its complex polyvalent binding
with multiple G-quadruplexes by single-molecule mechanical unfolding in laser
tweezers. We found telomestatin tetramer binds to multimeric telomeric G
quadruplexes >40 times stronger than monomeric quadruplexes, which can be
ascribed to the polyvalency induced unstacking of binding units (or PIU binding)
for G-quadruplexes. While stacking of telomestatin units in the tetramer imparts
steric hindrance for the ligand to access stand-alone G-quadruplexes, the
stacking disassembles to accommodate the potent polyvalent binding between the
tetramer ligand and multimeric G-quadruplexes. We anticipate this adaptive PIU
binding offers a generic mechanism to selectively target polymeric biomolecules
prevalent inside cells.
PMID- 28505454
TI - Perturbation-Response Scanning Reveals Key Residues for Allosteric Control in
Hsp70.
AB - Hsp70 molecular chaperones play an important role in maintaining cellular
homeostasis, and are implicated in a wide array of cellular processes, including
protein recovery from aggregates, cross-membrane protein translocation, and
protein biogenesis. Hsp70 consists of two domains, a nucleotide binding domain
(NBD) and a substrate binding domain (SBD), each of which communicates via an
allosteric mechanism such that the protein interconverts between two functional
states, an ATP-bound open conformation and an ADP-bound closed conformation. The
exact mechanism for interstate conversion is not as yet fully understood.
However, the ligand-bound states of the NBD and SBD as well as interactions with
cochaperones such as DnaJ and nucleotide exchange factor are thought to play
crucial regulatory roles. In this study, we apply the perturbation-response
scanning (PRS) method in combination with molecular dynamics simulations as a
computational tool for the identification of allosteric hot residues in the large
multidomain Hsp70 protein. We find evidence in support of the hypothesis that
substrate binding triggers ATP hydrolysis and that the ADP-substrate complex
favors interstate conversion to the closed state. Furthermore, our data are in
agreement with the proposal that there is an allosterically active intermediate
state between the open and closed states and vice versa, as we find evidence that
ATP binding to the closed structure and peptide binding to the open structure
allosterically "activate" the respective complexes. We conclude our analysis by
showing how our PRS data fit the current opinion on the Hsp70 conformational
cycle and present several allosteric hot residues that may provide a platform for
further studies to gain additional insight into Hsp70 allostery.
PMID- 28505455
TI - Interaction of Multiple Particles with a Solidification Front: From Compacted
Particle Layer to Particle Trapping.
AB - The interaction of solidification fronts with objects such as particles,
droplets, cells, or bubbles is a phenomenon with many natural and technological
occurrences. For an object facing the front, it may yield various fates, from
trapping to rejection, with large implications regarding the solidification
pattern. However, whereas most situations involve multiple particles interacting
with each other and the front, attention has focused almost exclusively on the
interaction of a single, isolated object with the front. Here we address
experimentally the interaction of multiple particles with a solidification front
by performing solidification experiments of a monodisperse particle suspension in
a Hele-Shaw cell with precise control of growth conditions and real-time
visualization. We evidence the growth of a particle layer ahead of the front at a
close-packing volume fraction, and we document its steady-state value at various
solidification velocities. We then extend single-particle models to the situation
of multiple particles by taking into account the additional force induced on an
entering particle by viscous friction in the compacted particle layer. By a force
balance model this provides an indirect measure of the repelling mean
thermomolecular pressure over a particle entering the front. The presence of
multiple particles is found to increase it following a reduction of the thickness
of the thin liquid film that separates particles and front. We anticipate the
findings reported here to provide a relevant basis to understand many complex
solidification situations in geophysics, engineering, biology, or food
engineering, where multiple objects interact with the front and control the
resulting solidification patterns.
PMID- 28505456
TI - Self-Polymerization of Dopamine in Acidic Environments without Oxygen.
AB - An alkaline environment and the presence of oxygen are essential requirements for
dopamine polymerization. In this study, we are the first to demonstrate the self
polymerization of dopamine through plasma-activated water (PAW) under acidic
environments (pH < 5.5). Resulting poly(dopamine) (PDA) was characterized using
Nanosizer, SEM, FTIR, UV-vis, 1H NMR, and fluorescence spectrophotometers and
proved to have similar physical and chemical properties to those polymerized
under a basic condition, except that the PDA particles formed in PAW were more
stable and hardly aggregated at varied pHs. The PAW polymerization method avoids
alkaline solutions and the presence of oxygen and thus extends the applications
of dopamine polymerization, particularly in biomedical and pharmaceutical
sciences.
PMID- 28505457
TI - Molecular and Biocompatibility Characterization of Red Blood Cell Membrane
Targeted and Cell-Penetrating-Peptide-Modified Polymeric Nanoparticles.
AB - Red blood cells (RBCs) express a variety of immunomodulatory markers that enable
the body to recognize them as self. We have shown that RBC membrane glycophorin A
(GPA) receptor can mediate membrane attachment of protein therapeutics. A
critical knowledge gap is whether attaching drug-encapsulated nanoparticles (NPs)
to GPA and modification with cell-penetrating peptide (CPP) will impact binding,
oxygenation, and the induction of cellular stress. The objective of this study
was to formulate copolymer-based NPs containing model fluorescent-tagged bovine
serum albumin (BSA) with GPA-specific targeting ligands such as ERY1 (ENPs),
single-chain variable antibody (scFv TER-119, SNPs), and low-molecular-weight
protamine-based CPP (LNPs) and to determine their biocompatibility using a
variety of complementary high-throughput in vitro assays. Experiments were
conducted by coincubating NPs with RBCs at body temperature, and biocompatibility
was evaluated by Raman spectroscopy, hemolysis, complement lysis, and oxidative
stress assays. Data suggested that LNPs effectively targeted RBCs, conferring 2
fold greater uptake in RBCs compared to ENPs and SNPs. Raman spectroscopy results
indicated no adverse effect of NP attachment or internalization on the
oxygenation status of RBCs. Cellular stress markers such as glutathione,
malondialdehyde, and catalase were within normal limits, and complement-mediated
lysis due to NPs was negligible in RBCs. Under the conditions tested, our data
demonstrates that molecular targeting of the RBC membrane is a feasible
translational strategy for improving drug pharmacokinetics and that the proposed
high-throughput assays can prescreen diverse NPs for preclinical and clinical
biocompatibility.
PMID- 28505458
TI - Position-Specific 13C Fractionation during Liquid-Vapor Transition Correlated to
the Strength of Intermolecular Interaction in the Liquid Phase.
AB - The relationship between the strength of the intermolecular interaction in liquid
and the position-specific 13C fractionation observed during distillation was
investigated. A range of molecules showing different intermolecular interactions
in terms of mode and intensity were incorporated in the study. Although it had
previously been suggested that during evaporation the diffusive 13C isotope
effect in the thin liquid layer interfaced with vapor is not position-specific,
herein we show that this is not the case. In particular, the position-specific
effect was demonstrated for a series of alcohols. Our hypothesis is that
intermolecular interactions in the liquid phase are the source of position
specific 13C fractionation observed on the molecule. A clear trend is observed
between the 13C isotope effect of the carbon bearing the heteroatom of chemical
function and the relative permittivity, the solvent hydrogen bond acidity, and
the solvent hydrogen bond basicity, while only a weak trend was observed when
using the 13C content of the whole molecule. Furthermore, two families of
products appeared when using the hydrogen bond acidity parameter for the
correlation by distinguishing H-acceptor and H-donor molecules from those H
acceptors only. This strongly reinforces the hypothesis of an important role of
the 13C positioned close to the interaction center.
PMID- 28505459
TI - Inhibition of Human Serum Albumin Fibrillation by Two-Dimensional Nanoparticles.
AB - The formation and deposition of amyloid fibrils have been linked to the
pathogenesis of numerous debilitating neurodegenerative disorders. Serum albumins
serve as good model proteins for understanding the molecular mechanisms of
protein aggregation and fibril formation. Graphene-based nanotherapeutics appear
to be promising candidates for designing inhibitors of protein fibrillation. The
inhibitory effect of graphene oxide (GO) nanoparticles on the fibrillation of
human serum albumin (HSA) in an in vitro mixed solvent system has been
investigated. The methods used include ThT fluorescence, ANS binding, Trp
fluorescence, circular dichroism, fluorescence microscopy, field-emission
scanning electron microscopy, and high-resolution transmission electron
microscopy. It was observed that GO inhibits HSA fibrillation and forms
agglomerates with beta-sheet rich prefibrillar species. Binding of GO prevents
the formation of mature fibrils with characteristic cross-beta sheet but does not
promote refolding to the native state.
PMID- 28505460
TI - Thermal Management in Nanofiber-Based Face Mask.
AB - Face masks are widely used to filter airborne pollutants, especially when
particulate matter (PM) pollution has become a serious concern to public health.
Here, the concept of thermal management is introduced into face masks for the
first time to enhance the thermal comfort of the user. A system of nanofiber on
nanoporous polyethylene (fiber/nanoPE) is developed where the nanofibers with
strong PM adhesion ensure high PM capture efficiency (99.6% for PM2.5) with low
pressure drop and the nanoPE substrate with high-infrared (IR) transparency
(92.1%, weighted based on human body radiation) results in effective radiative
cooling. We further demonstrate that by coating nanoPE with a layer of Ag, the
fiber/Ag/nanoPE mask shows a high IR reflectance (87.0%) and can be used for
warming purposes. These multifunctional face mask designs can be explored for
both outdoor and indoor applications to protect people from PM pollutants and
simultaneously achieve personal thermal comfort.
PMID- 28505461
TI - Spatial-Temporal Imaging of Anisotropic Photocarrier Dynamics in Black
Phosphorus.
AB - As an emerging single elemental layered material with a low symmetry in-plane
crystal lattice, black phosphorus (BP) has attracted significant research
interest owing to its unique electronic and optoelectronic properties, including
its widely tunable bandgap, polarization-dependent photoresponse and highly
anisotropic in-plane charge transport. Despite extensive study of the steady
state charge transport in BP, there has not been direct characterization and
visualization of the hot carriers dynamics in BP immediately after
photoexcitation, which is crucial to understanding the performance of BP-based
optoelectronic devices. Here we use the newly developed scanning ultrafast
electron microscopy (SUEM) to directly visualize the motion of photoexcited hot
carriers on the surface of BP in both space and time. We observe highly
anisotropic in-plane diffusion of hot holes with a 15 times higher diffusivity
along the armchair (x-) direction than that along the zigzag (y-) direction. Our
results provide direct evidence of anisotropic hot carrier transport in BP and
demonstrate the capability of SUEM to resolve ultrafast hot carrier dynamics in
layered two-dimensional materials.
PMID- 28505462
TI - Giant Gating Tunability of Optical Refractive Index in Transition Metal
Dichalcogenide Monolayers.
AB - We report that the refractive index of transition metal dichacolgenide (TMDC)
monolayers, such as MoS2, WS2, and WSe2, can be substantially tuned by >60% in
the imaginary part and >20% in the real part around exciton resonances using
complementary metal-oxide-semiconductor (CMOS) compatible electrical gating. This
giant tunablility is rooted in the dominance of excitonic effects in the
refractive index of the monolayers and the strong susceptibility of the excitons
to the influence of injected charge carriers. The tunability mainly results from
the effects of injected charge carriers to broaden the spectral width of
excitonic interband transitions and to facilitate the interconversion of neutral
and charged excitons. The other effects of the injected charge carriers, such as
renormalizing bandgap and changing exciton binding energy, only play negligible
roles. We also demonstrate that the atomically thin monolayers, when combined
with photonic structures, can enable the efficiencies of optical absorption
(reflection) tuned from 40% (60%) to 80% (20%) due to the giant tunability of the
refractive index. This work may pave the way toward the development of field
effect photonics in which the optical functionality can be controlled with CMOS
circuits.
PMID- 28505464
TI - Treatment of the cardiac hypertrophic response and heart failure with ginseng,
ginsenosides, and ginseng-related products.
AB - Heart failure is a major medical and economic burden throughout the world.
Although various treatment options are available to treat heart failure, death
rates in both men and women remain high. Potential adjunctive therapies may lie
with use of herbal medications, many of which possess potent pharmacological
properties. Among the most widely studied is ginseng, a member of the genus Panax
that is grown in many parts of the world and that has been used as a medical
treatment for a variety of conditions for thousands of years, particularly in
Asian societies. There are a number of ginseng species, each possessing distinct
pharmacological effects due primarily to differences in their bioactive
components including saponin ginsenosides and polysaccharides. While experimental
evidence for salutary effects of ginseng on heart failure is robust, clinical
evidence is less so, primarily due to a paucity of large-scale well-controlled
clinical trials. However, there is evidence from small trials that ginseng
containing Chinese medications such as Shenmai can offer benefit when
administered as adjunctive therapy to heart failure patients. Substantial
additional studies are required, particularly in the clinical arena, to provide
evidence for a favourable effect of ginseng in heart failure patients.
PMID- 28505465
TI - Isomerization of glucose into fructose by environmentally friendly Fe/beta
zeolite catalysts.
AB - Herein, the environmentally friendly Fe/beta zeolite for glucose isomerization to
fructose in aqueous media was reported for the first time. The effects of various
reaction conditions including reaction temperature, reaction time, catalyst
dosage, etc. on the isomerization reaction over Fe/beta zeolite were studied in
detail. Under the optimized conditions, yield of fructose higher than 20% were
obtained. Moreover, the Fe/beta zeolite catalysts were stable and remained
constant catalytic activity after five consecutive runs. The possible active Fe
species for isomerization of glucose in Fe/beta zeolite is also discussed.
PMID- 28505463
TI - In Vivo Pretargeted Imaging of HER2 and TAG-72 Expression Using the HaloTag
Enzyme.
AB - A novel pretargeted SPECT imaging strategy based on the HaloTag enzyme has been
evaluated for the first time in a living system. To determine the efficacy of
this approach, two clinically relevant cancer biomarkers, HER2 and TAG-72, were
selected to represent models of internalizing and noninternalizing antigens,
respectively. In MDA-MB-231/H2N (HER2-expressing) and LS174T (TAG-72-expressing)
xenograft tumors in mice, pretargeting experiments were performed in which
HaloTag-conjugated derivatives of the antibodies trastuzumab (anti-HER2) or CC49
(anti-TAG-72) were utilized as primary agents, and the small molecule HaloTag
ligands 111In-HTL-1, -2, and -3 were evaluated as secondary agents. While this
approach was not sufficiently sensitive to detect the internalizing HER2 antigen,
pretargeting experiments involving the most optimal secondary agent, 111In-HTL-3,
were successful in detecting the noninternalizing antigen TAG-72 and provided
high-contrast SPECT images at 4 and 24 h postinjection.
PMID- 28505466
TI - The conceptualization of emotion regulation difficulties, and its association
with posttraumatic stress symptoms in traumatized refugees.
AB - This study investigated the conceptualization of emotion regulation difficulties
in a sample of refugees with varying levels of posttraumatic stress (PTS), and
examined whether specific emotion regulation difficulties were associated with
PTS severity. Refugees were administered an abbreviated version of the
Difficulties in Emotion Regulation Scale, the PTSD Symptom Scale - Interview
Version, and the Harvard Trauma Questionnaire. Confirmatory Factor Analysis was
used to examine model fit for the 6-factor model originally proposed by the
developers of the DERS and the more recently proposed 5-factor model that
excludes the awareness subscale. Both models displayed adequate fit. After
controlling for age, gender, time in Australia, and trauma exposure, the clarity
and strategies subscales were significantly associated with PTS severity. The
association between impaired emotional clarity and reduced agency related to
accessing regulation strategies and PTS severity in this refugee sample
highlights the need for further research to assess interventions that target
these disruptions in refugees.
PMID- 28505467
TI - Low cholesterol level as a risk marker of inpatient and post-discharge violence
in acute psychiatry - A prospective study with a focus on gender differences.
AB - Several studies indicate an association between low levels of serum cholesterol
and aggressive behaviour, but prospective studies are scarce. In this
naturalistic prospective inpatient and post-discharge study from an acute
psychiatric ward, we investigated total cholesterol (TC) and high-density
lipoprotein (HDL) as risk markers of violence. From March 21, 2012, to March 20,
2013, 158 men and 204 women were included. TC and HDL were measured at admission.
Violence was recorded during hospital stay and for the first 3 months post
discharge. Univariate and multivariate binary logistic regression were used to
estimate associations between low TC and low HDL and violence. Results showed
that HDL level was significantly inversely associated with violence during
hospital stay for all patients. For men, but not for women, HDL level was
significantly inversely associated with violence the first 3 months post
discharge. Results indicate that low HDL is a risk marker for inpatient and post
discharge violence in acute psychiatry and also suggest gender differences in HDL
as a risk marker for violence.
PMID- 28505468
TI - Comparison of insight and clinical variables in homeless and non-homeless
psychiatric inpatients in China.
AB - There are no published data on insight in homeless patients with psychiatric
disorders in China. This study examined insight in homeless and non-homeless
Chinese psychiatric inpatients in relation to demographic and clinical variables.
A total of 278 homeless and 222 non-homeless inpatients matched in age and gender
were included in the study. Demographic and clinical characteristics were
collected based on a review of medical charts and a clinical interview with
standardized instruments. Insight was evaluated with the Insight and Treatment
Attitudes Questionnaire. Altogether 20.5% of homeless inpatients and 43.7% of the
non-homeless controls had good insight. Compared with homeless inpatients with
impaired insight, homeless inpatients with good insight had higher physical
quality of life, longer duration of illness and less severe positive and negative
symptoms. Impaired insight appeared more common in homeless psychiatric
inpatients in China. Further studies should address the need for effective
therapeutic interventions that promote homeless patients' insight.
PMID- 28505469
TI - The association between immune markers and recent suicide attempts in patients
with serious mental illness: A pilot study.
AB - Previous studies have identified elevations in markers of gastrointestinal
inflammation in schizophrenia and mood disorders but studies have not measured
the association between these markers and recent suicide attempts. We assessed
210 patients receiving treatment for schizophrenia, bipolar disorder, or major
depression. We employed the Columbia Suicide Severity Rating Scale to identify
recent and lifetime suicide attempts (actual, aborted, and interrupted).
Psychiatric participants and a control group of 72 individuals without a
psychiatric disorder had a blood sample drawn from which were measured specific
markers of gastrointestinal inflammation and also C-Reactive protein (CRP). A
total of 20 (10%) of psychiatric participants had a suicide attempt in the
previous one month and 95 (45%) an attempt during their lifetime but not in the
previous one month. The recent attempters had significantly elevated levels of
antibodies to yeast mannan from Saccharomyces cerevisiae (ASCA), the food antigen
gliadin, and bacterial lipopolysaccharide (LPS) compared with the non-psychiatric
group when adjusting for demographic and clinical variables. These markers were
not elevated in individuals with a past, but not recent, suicide attempt history.
Our study indicates that there is evidence of gastrointestinal inflammation in
some individuals who have had a recent suicide attempt.
PMID- 28505471
TI - A prospective examination of risk factors in the development of intrusions
following a trauma analog.
AB - Several factors have been linked to the severity of posttraumatic distress,
although retrospective designs in much of the literature limit conclusions
regarding the temporal relation between risk factors and corresponding symptoms.
To address these concerns, the current project employed an analog trauma paradigm
to assess the impact of background characteristics, stress response, and post
stressor affect regulation on subjective distress and intrusive memories
experienced during the subsequent processing of emotional stimuli. University
students (N = 184; 56% female, 42% White/Non-Hispanic) were shown graphic scenes
of a televised suicide. Physiological activation was recorded during exposure
with emotion ratings collected following the film. Participants then viewed a
sadness- or humor-eliciting prime under instructions to inhibit or naturally
express emotion. Intrusions experienced during the priming film and residual
distress at study's conclusion were rated prior to debriefing. Hierarchical
regression identified reductions in emotional valence as a robust predictor of
intrusions and distress. Sympathetic activation and exposure to the sadness prime
were associated with intrusion frequency, whereas attenuated parasympathetic
response predicted intrusion intensity. Expressive inhibition demonstrated a
unique association with residual distress. Results suggest peritraumatic
processes and post-exposure factors may hold more prominent relations with
immediate trauma-related distress as compared to pre-existing survivor
characteristics.
PMID- 28505470
TI - Pilot test of a novel food response and attention training treatment for obesity:
Brain imaging data suggest actions shape valuation.
AB - Elevated brain reward and attention region response, and weaker inhibitory region
response to high-calorie food images have been found to predict future weight
gain. These findings suggest that an intervention that reduces reward and
attention region response and increases inhibitory control region response to
such foods might reduce overeating. We conducted a randomized pilot experiment
that tested the hypothesis that a multi-faceted food response and attention
training with personalized high- and low-calorie food images would produce
changes in behavioral and neural responses to food images and body fat compared
to a control training with non-food images among community-recruited
overweight/obese adults. Compared to changes observed in controls, completing the
intervention was associated with significant reductions in reward and attention
region response to high-calorie food images (Mean Cohen's d = 1.54), behavioral
evidence of learning, reductions in palatability ratings and monetary valuation
of high-calorie foods (p = 0.009, d's = 0.92), and greater body fat loss over a 4
week period (p = 0.009, d = 0.90), though body fat effects were not significant
by 6-month follow-up. Results suggest that this multifaceted response and
attention training intervention was associated with reduced reward and attention
region responsivity to food cues, and a reduction in body fat. Because this
implicit training treatment is both easy and inexpensive to deliver, and does not
require top-down executive control that is necessary for negative energy balance
obesity treatment, it may prove useful in treating obesity if future studies can
determine how to create more enduring effects.
PMID- 28505472
TI - Improvement of older-person-specific QOL after hearing aid fitting and its
relation to social interaction.
AB - PURPOSE: This study aimed to investigate whether hearing aids use is associated
with improvement of older-person-specific QOL and whether social interactions
modify the association. METHODS: The WHOQOL-OLD questionnaire was answered by 105
older adults aged 60 to 90 years who were newly fitted hearing aids on the day of
fitting and at 2 - 6 months afterward. The associations between the daily hours
of hearing aid usage and social relations with changes in the WHOQOL-OLD total
score after hearing aids fitting were estimated adjusting for possible
confounders. RESULTS: Older persons with hearing loss experienced significant
increases in WHOQOL-OLD total score after hearing aid fitting. Regular use of
hearing aid was associated with a greater increase in the total score. The
combined categorical variable of social relations and hearing aid usage revealed
no separate effects of these two variables, but a combined effect; only those
with frequent social interactions who used their hearing aid regularly had a
significantly greater increase in WHOQOL-OLD total score. CONCLUSION: This
study's findings indicate that hearing aid fitting may be associated with a
subsequent improvement in older-person-specific QOL by improvements in hearing
due to the hearing aid, and possibly enhanced communication opportunities.
PMID- 28505473
TI - The protective study about alleviation of simvastatin on the damages of PEG-BNs
in mice.
AB - Boron nitride nanoparticles have been proved to cause various toxicities, damages
or inflammations after entering into in vivo in previous reports. However, up to
now, there are rare investigations about the alleviation of damages caused by
nanoparticles in vivo through natural small molecule drugs. Therefore, in this
work, PEG-BNs with high solubility was successfully synthesized, and then their
biodistribution in mice were studied using radiolabeling technique. And the
heart, lung, liver, spleen, kidney tissues and blood samples were done for
histology and biochemical analysis. The results showed that PEG-BNs were mainly
distributed in lung, liver, kidney and spleen with an obviouse decreasing
distribution as the experimental time was increasing. Besides, significantly
serum biochemical and tissue pathological changes induced by PEG-BNs were
confirmed. Moreover, after simvastatin (SST) exposure to the PEG-BNs model mice,
the damages and biochemical indexes were recovered significantly as compared to
the single exposure group mice in serum, which indicates a good treatment effect
on the toxicity of PEG-BNs in vivo in mice. This study provides some basic data
and useful information for the treatment of damages caused by the nanoparticles
in mice in the future.
PMID- 28505474
TI - The effect of passive and active exposure to tobacco smoke on lipid profile
parameters and the activity of certain membrane enzymes in the blood of women in
the first trimester of pregnancy.
AB - The effect of tobacco smoke on lipid peroxidation, the lipid profile and membrane
bound enzymatic activity in the first trimester of pregnancy was investigated. In
the plasma of women with active exposure to tobacco smoke, we have found
increased lipid peroxidation and higher total concentrations of cholesterol,
triglycerides and low-density lipoproteins in the blood, as well as a decreased
concentration of high-density lipoproteins. A higher concentration of low-density
lipoproteins and a lower concentration of high-density lipoproteins were also
found in the plasma of passive smokers. In contrast, women who smoked before
pregnancy had only a higher low-density lipoprotein concentration. In the group
of active and passive smoking women, lower arylesterase and phosphotriesterase
activities of paraoxonase were observed, while the lactonase activity of
paraoxonase decreased only in the group of active smoking women. In women with
active exposure to tobacco smoke, a higher activity level of alanine
aminopeptidase and gamma-glutamyltransferase in the plasma was found. It is
important to monitor the lipid profile during pregnancy, especially when exposure
to tobacco smoke occurs.
PMID- 28505475
TI - Colorectal cancer subtypes: Translation to routine clinical pathology.
AB - Colorectal cancer (CRC) is the second most common cause of cancer death in
Europe. Although outcomes have improved, it is clear that from a genomic
standpoint CRC is not one disease, but a heterogeneous group of malignancies that
arise within one organ. Given that different subtypes have different outcomes,
the ability to subtype tumours in the clinic would be highly favourable, enabling
optimal treatment for individual patients. In 2015, a consortium proposed four
consensus subtypes for CRC (MSI immune, canonical, metabolic, and mesenchymal)
based on six classifications systems reported to have prognostic value. However,
genomic assessment of tumours is not readily translated into routine pathology
with a need for standardisation and reproducibility of assessment.
Immunohistochemistry is widely used in routine pathology, and would present a
more readily translatable method for subtyping CRC tumours. Therefore, the
literature was reviewed to characterise the genomic and phenotypic features
associated with each subtype, with the aim of enabling subtyping of CRC to be
taken forward into routine clinical practice.
PMID- 28505476
TI - Gender difference in the association between lower muscle mass and metabolic
syndrome independent of insulin resistance in a middle-aged and elderly Taiwanese
population.
AB - BACKGROUND: Loss of muscle mass was reported to be associated with metabolic
syndrome (MetS), but little is known about the gender difference. Thus, the aim
of this study was to evaluate the relationship between lower muscle mass and MetS
and determine whether there was any gender difference or not. METHODS: A total of
394 middle-aged and elderly Taiwanese adults (138 males and 256 females) were
enrolled and completed our health survey. They were stratified into three groups
according to appendicular skeletal muscle mass divided by weight. Participants
distributed into the lower tertile were defined as people having lower muscle
mass. MetS was defined using the Adult Treatment Panel III Asian diagnostic
criteria. Multivariate logistic regression analysis was performed to assess the
association between muscle and MetS. RESULTS: We found an inverse association
between MetS and muscle mass in both males and females. Participants with lower
muscle mass had a higher risk of MetS in univariate analysis. The same results
were observed when adjusted for age and when also adjusted for living condition
factors. However, after additional adjustment for potential confounders and HOMA
IR, we only found it to be statistically significant in the female group (OR in
male=3.60; 95% CI=0.62-20.83, p=0.153; OR in female=3.03; 95% CI=1.16-7.94,
p=0.024). CONCLUSIONS: We examined the relationship between lower muscle mass and
metabolic syndrome in a middle-aged and elderly Taiwanese population. We found
that lower muscle mass was associated with the risk of metabolic syndrome in the
aged, particularly in females.
PMID- 28505477
TI - Knowledge, behavioral practices, and experiences of outdoor fallers: Implications
for prevention programs.
AB - OBJECTIVE: Although the epidemiology and prevention of falls has been well
studied, the focus has been on indoor rather than outdoor falls. Older adults'
knowledge of outdoor risk factors and their outdoor fall prevention practices
have not been examined. To fill this gap, and to inform the development of a
prevention program, we sought to explore the experiences and fall prevention
knowledge and practices of older adults who had sustained an outdoor fall.
METHODS: A cross-sectional study using random digit telephone dialing was used to
survey community dwelling seniors (N=120) across the five boroughs of New York
City. We used the Outdoor Falls Questionnaire (OFQ), a valid and reliable tool as
the survey instrument. Perceived outdoor fall risks, strategies used for
prevention, and outdoor fall experiences were examined. SPSS version 21 was used
for descriptive analysis of participant characteristics and to determine
frequencies of perceived outdoor fall risks and strategies used for prevention.
Phenomenological analysis was used with the qualitative data. Qualitative and
quantitative data were analyzed separately and a mixed methods matrix was used to
interpret and integrate the findings. RESULTS: Analysis revealed diverse unmet
education and training needs including the importance of using single vision
glasses, understanding the fall risks associated with recreational areas and
parking lots, safe outdoor walking strategies, safe carrying of items on level
and uneven surfaces, as well as when walking up and down stairs, and safety in
opening/closing doors. CONCLUSIONS: Study findings are informative for outdoor
fall prevention programs as well as practice.
PMID- 28505478
TI - Dose assessment in environmental radiological protection: State of the art and
perspectives.
AB - Exposure to radiation is a potential hazard to humans and the environment. The
Fukushima accident reminded the world of the importance of a reliable risk
management system that incorporates the dose received from radiation exposures.
The dose to humans from exposure to radiation can be quantified using a well
defined system; its environmental equivalent, however, is still in a
developmental state. Additionally, the results of several papers published over
the last decade have been criticized because of poor dosimetry. Therefore, a
workshop on environmental dosimetry was organized by the STAR (Strategy for
Allied Radioecology) Network of Excellence to review the state of the art in
environmental dosimetry and prioritize areas of methodological and guidance
development. Herein, we report the key findings from that international workshop,
summarise parameters that affect the dose animals and plants receive when exposed
to radiation, and identify further research needs. Current dosimetry practices
for determining environmental protection are based on simple screening dose
assessments using knowledge of fundamental radiation physics, source-target
geometry relationships, the influence of organism shape and size, and knowledge
of how radionuclide distributions in the body and in the soil profile alter dose.
In screening model calculations that estimate whole-body dose to biota the shapes
of organisms are simply represented as ellipsoids, while recently developed
complex voxel phantom models allow organ-specific dose estimates. We identified
several research and guidance development priorities for dosimetry. For external
exposures, the uncertainty in dose estimates due to spatially heterogeneous
distributions of radionuclide contamination is currently being evaluated.
Guidance is needed on the level of dosimetry that is required when screening
benchmarks are exceeded and how to report exposure in dose-effect studies,
including quantification of uncertainties. Further research is needed to
establish whether and how dosimetry should account for differences in tissue
physiology, organism life stages, seasonal variability (in ecology, physiology
and radiation field), species life span, and the proportion of a population that
is actually exposed. We contend that, although major advances have recently been
made in environmental radiation protection, substantive improvements are required
to reduce uncertainties and increase the reliability of environmental dosimetry.
PMID- 28505479
TI - Women's self-reported experience of unplanned caesarean section: Results of a
Swedish study.
AB - BACKGROUND: women's experience of emergency caesarean section is often described
as less positive compared to a vaginal birth or a planned caesarean section.
Midwifery care for women where deviations from a normal birth process are present
is a challenge. The aim of study was to compare self-reported birth outcomes for
women undergoing birth through spontaneous onset of labour between those who
actually had a vaginal birth and those who eventually had an emergency caesarean
section. DESIGN AND SETTING: the study was part of a prospective longitudinal
cohort study of parents' experiences, attitudes, and beliefs related to
childbirth. METHOD AND FINDINGS: questionnaires were answered by 870 women in
midpregnancy, two months postpartum and one year after birth. 766 women (88%) had
a vaginal birth, and 104 (12%) had an emergency caesarean section. The most
common indications of emergency caesarean section were dystocia, foetal distress,
and malpresentation. Women in the emergency caesarean group were more likely to
be primiparous (59.6%) and have a body mass index > 30 (10.7%). Childbirth fear
was twice as common among these women, and they were more likely to have
preferred a caesarean delivery when asked about birth preference in the middle of
pregnancy (OR 3.7, Cl 1.8-7.5). Induction of labour (OR 2.5, Cl 1.6-4.0), the use
of oxytocin for augmentation (OR 1.9, Cl 1.3-2.9), and the use of epidural as
pain relief during labour (OR 5.6, Cl 3.6-8.7) were more common among women
having an emergency caesarean section. Transport of the new-born to a neonatal
intensive care unit was three times as common. More than a third (37%) of the
women in the caesarean group preferred a caesarean section in case of another
birth. Childbirth fear was more common one year after birth with 32% of these
women describing their fear as moderate or strong (OR 3.6, CI 2.1-6.0). KEY
CONCLUSIONS: women undergoing emergency caesarean section are more likely to
experience fear and to have a negative birth experience. It is essential for the
midwife to promote a sense of control, involve the woman in the procedure, and
create security in a threatening situation. This is made possible in relationship
characterized by mutuality, trust, on-going dialogue, shared responsibility, and
enduring presence.
PMID- 28505480
TI - Triphenyltin(IV) benzoates with diazenyl/imino scaffold exhibiting remarkable
apoptosis mediated by reactive oxygen species.
AB - The cytotoxic potency of a series of triphenyltin(IV) compounds of general
composition [Ph3Sn(Ln)] (1-6) has been probed in vitro employing MDA-MB-231
(human breast cancer) and HeLa (human cervical cancer) cell lines, where Ln=L1-3;
isomeric 2/3/4-{(E)-2-[4-(dimethylamino)phenyl]diazenyl}benzoates and L4-6 are
their corresponding isoelectronic imino analogues 2/3/4-[(E)-{[4
(dimethylamino)phenyl]methylidene}amino]benzoates. Compounds 1-6 have been
characterized by elemental analysis and their spectroscopic properties were
studied using IR and NMR (1H, 13C, 119Sn) techniques. The molecular structures of
a pro-ligand 2-[(E)-{[4-(dimethylamino)phenyl]methylidene}amino]benzoic acid
(HL4) and two representative molecules, Ph3Sn(L2) 2 and Ph3Sn(L5) 5, have been
determined by X-ray crystallography. Structural analyses of 2 and 5 revealed
distorted tetrahedral geometries within C3O donor sets owing to monodentate modes
of coordination of the respective carboxylate ligands, close intramolecular
Sn...O(carbonyl) interactions notwithstanding. Cytotoxic studies in vitro in MDA
MB-231 and HeLa cell lines revealed high activity, in sub-micromolar range, for
all investigated compounds. Among these, 1 and 3 exhibited potent cytotoxicity
most effectively towards MDA-MB-231 cells with a IC50 value of 1.19 and 1.44MUM,
respectively, whereas 5 showed remarkable activity towards HeLa cells with a IC50
value of 0.88MUM, yet the series of compounds had minimal cytotoxic effect on
normal HEK 293 (human embryonic kidney) cell line. The underlying investigation
suggested that the compounds exert potent antitumor effect by elevating
intracellular reactive oxygen species generation and cause delay in cell cycle by
inhibiting cells at G2/M phase. The results presented herein suggest further
development of this class of triphenyltin(IV) compounds-based drugs as potential
anti-cancer therapies should be pursued.
PMID- 28505481
TI - Altered development, oxidative stress and DNA damage in Leptodactylus chaquensis
(Anura: Leptodactylidae) larvae exposed to poultry litter.
AB - Poultry litter (PL), which is usually used as organic fertilizer, is a source of
nutrients, metals, veterinary pharmaceuticals and bacterial pathogens, which,
through runoff, may end up in the nearest aquatic ecosystems. In this study,
Leptodactylus chaquensis at different development stages (eggs, larval stages 28
and 31 here referred to as stages I, II and III respectively) were exposed to PL
test sediments as follows: 6.25% (T1), 12.5% (T2); 25% (T3); 50% (T4); 75% (T5);
100% PL (T6) and to dechlorinated water as control. Larval survival, development
endpoints (growth rate -GR-, development rate -DR-, abnormalities), antioxidant
enzyme activities (Catalase -CAT- and Glutathione-S-Transferase -GST-), and
genotoxic effect (DNA damage index by the Comet assay) were analyzed at different
times. In stage I, no egg eclosion was observed in treatments T3-T6, and 50% of
embryo mortality was recorded after 24h of exposure to T2. In stages II and III,
mortality in treatments T3-T6 reached 100% between 24 and 48h. In the three
development stages evaluated, the DR and GR were higher in controls than in PL
treatments (T1, T2), except for those T1-treated larvae of stage II. Larvae of
stage I showed five types of morphological abnormalities, being diamond body
shape and lateral displacement of the intestine the most prevalent in T1, whereas
larvae of stages II and III presented lower prevalence of abnormalities. In stage
I, CAT activity was similar to that of control (p>0.05), whereas it was higher in
T1- and T2- treated larvae of stages II and III than controls (p<0.05). In stages
I and III, GST activity was similar to that of controls (p>0.05), whereas it was
inhibited in T1-treated larvae of stage II (p<0.05). T1- and T2-treated larvae of
stages II and III caused higher DNA damage respect to controls (p<0.05), varying
from medium to severe damage (comet types II, III and IV). These results showed
that PL treatments altered development and growth and induced oxidative stress
and DNA damage, resulting ecotoxic for L. chaquensis larvae.
PMID- 28505482
TI - Conservation efforts of captive golden takin (Budorcas taxicolor bedfordi) are
potentially compromised by the elevated chemical elements exposure.
AB - Chemical elements exposure of endangered golden takins (Budorcas taxicolor
bedfordi) living in the Qinling Mountains and in a captive breeding center was
assessed by analyzing fecal samples. Concentrations of As, Co, Cr, Cu, Ni and Se
were significantly higher in the feces of captive golden takins than the wild.
There was no significant difference in the fecal concentrations of Cd, Mn, Hg, Pb
or Zn for wild and captive animals. The element concentration of fecal samples
collected from captive animals varied seasonally, with concentrations being
lowest in spring and highest in winter and/or autumn. The food provided to
captive animals varied both in the composition and the concentration of element
present. Consumptions of feedstuff and additional foods such as D. sanguinalis
and A. mangostanus for the captive golden takins were identified as the possible
sources of chemical element exposure. The estimations of dietary intake of most
elements by captive takins were below the oral reference dose, except for As and
Pb, indicating that As and Pb were the key components which contributed to the
potential non-carcinogenic risk for captive golden takins. In conclusion, captive
golden takins were exposed to higher concentrations of chemical elements compared
with the wild, which were likely due to their dietary difference. Conservation
efforts of captive golden takin are potentially compromised by the elevated
chemical element exposure and effort should focus on providing uncontaminated
food for captive animals.
PMID- 28505483
TI - The effects of ingested aqueous aluminum on floral fidelity and foraging strategy
in honey bees (Apis mellifera).
AB - Pollinator decline is of international concern because of the economic services
these organisms provide. Commonly cited sources of decline are toxicants, habitat
fragmentation, and parasites. Toxicant exposure can occur through uptake and
distribution from plant tissues and resources such as pollen and nectar. Metals
such as aluminum can be distributed to pollinators and other herbivores through
this route especially in acidified or mined areas. A free-flying artificial
flower patch apparatus was used to understand how two concentrations of aluminum
(2mg/L and 20mg/L) may affect the learning, orientation, and foraging behaviors
of honey bees (Apis mellifera) in Turkey. The results show that a single dose of
aluminum immediately affects the floral decision making of honey bees potentially
by altering sucrose perception, increasing activity level, or reducing the
likelihood of foraging on safer or uncontaminated resource patches. We conclude
that aluminum exposure may be detrimental to foraging behaviors and potentially
to other ecologically relevant behaviors.
PMID- 28505484
TI - Arsenic speciation in the phloem exudates of rice and its role in arsenic
accumulation in rice grains.
AB - Arsenic (As) speciation in the phloem sap of rice plants and its role in As
accumulation in rice grains remain largely uncharacterized. In the present study,
we tested As chemical species in the phloem exudates of rice treated with
arsenate [As(V)], arsenite [As(III)], monomethylarsonic acid [MMA(V)], or
dimethylarsinic acid [DMA(V)]. As(V) was the main species (58%) in the phloem
exudates of As(V)-exposed rice, whereas As(III) predominated (69%) in As(III)
exposed rice. A large proportion of As(V) (41-45%) was observed in the phloem
exudates when rice was treated with methylated As species. High concentrations of
phytochelatins were detected in the phloem exudates when the As(V) treatment
level was increased. The role of phloem transport was analyzed by applying a +/
stem-girdling treatment to the rice plants, limiting phloem transport to the
grain in rice pulsed with As(III), As(V), MMA(V), or DMA(V). The findings of the
present study indicate that organic As is more mobile than inorganic As during
phloem transport. Phloem transport accounted for 54% of As(III), 56% of As(V),
100% of MMA(V), and 89% of DMA(V) transport to the grain. The total As
concentration and As(III) percentage in rice phloem and grain were significantly
affected by increasing the phosphate concentration in the medium.
PMID- 28505485
TI - Interventions affecting mortality in critically ill and perioperative patients: A
systematic review of contemporary trials.
AB - PURPOSE: Confounders in randomized controlled trials (RCTs) reporting significant
effects on mortality in critically ill patients using non-surgical techniques
have not been systematically explored. We aimed to identify factors unrelated to
the reported intervention that might have affected the findings and robustness of
such trials. METHODS: We searched Pubmed/MEDLINE for all RCTs on any non-surgical
interventions reporting an effect on unadjusted mortality in critically ill
patients between 1/1/2000 and 1/12/2015. We assessed: the number needed to
treat/harm (NNT or NNH), sample size, trial design (blinded/unblinded, single or
multinational, single or multicenter (sRCT or mRCT)), intention to treat (ITT)
analysis, and countries of origin. RESULTS: Almost half of RCTs were sRCTs.
Median sample size was small, and 1/3 were not analyzed according to ITT
principle. Lack of ITT analysis was associated with greater effect size
(p=0.0028). Harm was more likely in mRCTs (p=0.002) and/or in blinded RCTs
(p=0.003). Blinded RCTs had double sample size (p=0.007) and an increased NNT/NNH
(p=0.002). Finally, mRCTs had higher NNT (p=0.005) and NNH (p=0.02), and harm was
only detected in studies from Western countries (p=0.007). CONCLUSIONS: These
observations imply that major systematic biases exist and affect trial findings
irrespective of the intervention being studied.
PMID- 28505486
TI - Respiratory support techniques to avoid desaturation in critically ill patients
requiring endotracheal intubation: A systematic review and meta-analysis.
AB - PURPOSE: To evaluate which respiratory support method for critically ill patients
undergoing endotracheal intubation (ETI) is associated with less desaturation.
METHODS: We searched PubMed, Cochrane Library, Scopus and CINAHL databases. We
included randomized (RCT) and non-randomized (non-RCT) studies investigating any
method of respiratory support before/during ETI compared to a reference control.
RESULTS: Apneic oxygenation (ApOx) was the most commonly investigated respiratory
support technique for critically ill patients undergoing intubation (4 RCTs, 358
patients). Three of these studies investigated high-flow nasal cannula (HFNC) for
ApOx while standard nasal cannula was used in one. Globally, ApOx was associated
with higher minimum SpO2 value compared to those receiving ETI without ApOx (mean
difference 2.31%, 95% CI 0.42 to 4.20, p=0.02, I2=0%) but there were not
significant differences between groups in severe hypoxemia and intubation related
- complications. Concerning other techniques, noninvasive ventilation (NIV) was
compared to bag-valve mask in only one RCT and it reduced the degree of
desaturation. CONCLUSIONS: ApOx was significantly associated with higher minimum
SpO2 registered during the intubation procedure. Further studies are needed to
increase the number of included patients and demonstrate the benefit of ApOx and
of other respiratory support methods (e.g. NIV, HFNC).
PMID- 28505487
TI - Heroin refusal self-efficacy and preference for medication-assisted treatment
after inpatient detoxification.
AB - OBJECTIVE: An individual's self-efficacy to refuse using heroin in high-risk
situations is believed to minimize the likelihood for relapse. However, among
individuals completing inpatient heroin detoxification, perceived refusal self
efficacy may also reduce one's perceived need for medication-assisted treatment
(MAT), an effective and recommended treatment for opioid use disorder. In the
current study, we examined the relationship between heroin refusal self-efficacy
and preference for MAT following inpatient detoxification. METHOD: Participants
(N=397) were interviewed at the start of brief inpatient opioid detoxification.
Multiple logistic regression was used to estimate the adjusted association of
background characteristics, depressed mood, and perceived heroin refusal self
efficacy with preference for MAT. RESULTS: Controlling for other covariates,
depressed mood and lower perceived refusal self-efficacy were associated with a
significantly greater likelihood of expressing preference for MAT (versus no
MAT). CONCLUSIONS: Perceived ability to refuse heroin after leaving detox is
inversely associated with a heroin user's desire for MAT. An effective continuum
of care model may benefit from greater attention to patient's perceived refusal
self-efficacy during detoxification which may impact preference for MAT and long
term recovery.
PMID- 28505488
TI - Predictors of buprenorphine treatment success of opioid dependence in two
Baltimore City grassroots recovery programs.
AB - INTRODUCTION: Despite evidence for the efficacy of buprenorphine treatment in
primary care, few studies have identified factors associated with treatment
success, nor have such factors been evaluated in community settings. Identifying
correlates of treatment success can facilitate the development of treatment
models tailored for distinct populations, including low-income communities of
color. The current study examined client-level socio-demographic factors
associated with treatment success in community-based buprenorphine programs
serving vulnerable populations. METHODS: Data were abstracted from client records
for participants (N=445) who met DSM-IV criteria for opioid dependence and sought
treatment at one of Behavioral Health Leadership Institute's two community-based
recovery programs in Baltimore City from 2010 to 2015. Logistic regression
estimated the odds ratios of treatment success (defined as retention in treatment
for >=90days) by sociodemographic predictors including age, race, gender,
housing, legal issues and incarceration. RESULTS: The odds of being retained in
treatment >=90days increased with age (5% increase with each year of age;
p<0.001), adjusting for other sociodemographic factors. Clients who reported
unstable housing had a 41% decreased odds of remaining in treatment for 90 or
more days compared to clients who lived independently at intake. Treatment
success did not significantly differ by several other client-level
characteristics including gender, race, employment, legal issues and
incarceration. CONCLUSIONS: In vulnerable populations, the age factor appears
sufficiently significant to justify creating models formulated for younger
populations. The data also support attention to housing needs for people in
treatment. Findings from this paper can inform future research and program
development.
PMID- 28505489
TI - Anxiety sensitivity as a predictor of outcome in the treatment of obsessive
compulsive disorder.
AB - BACKGROUND AND OBJECTIVES: To address the fact that not all individuals who
receive cognitive-behavioral therapy (CBT) for obsessive-compulsive disorder
(OCD) exhibit complete symptom reduction, research has examined factors that
predict outcome; however, no studies have examined anxiety sensitivity (AS) as a
predictor of outcome of CBT for OCD. AS refers to the fear of anxious arousal
that results from mistaken beliefs about the dangerousness of anxiety-related
body sensations. It is important to understand whether AS influences OCD
treatment outcome, considering that (a) some obsessions directly relate to AS,
and (b) OCD patients with high AS may be reluctant to engage in anxiety-provoking
components of CBT for OCD. METHODS: Patients (N = 187) with a primary diagnosis
of OCD who received residential CBT for OCD participated in this study, which
involved completing a self-report battery at pre- and post-treatment. RESULTS:
Results supported study hypotheses, in that (a) baseline AS positively correlated
with baseline OCD severity, and (b) greater baseline AS prospectively predicted
higher posttreatment OCD symptom severity even after controlling for pretreatment
OCD and depression severity. LIMITATIONS: The study was limited by its use of an
older measure of AS, reliance on self-report measures, and nonstandardized
treatment across participants. CONCLUSIONS: Findings highlight the importance of
AS in the nature and treatment of OCD. Clinical implications and future
directions are discussed.
PMID- 28505491
TI - Development of suitable method for large-scale urinary glucocorticoid analysis by
liquid chromatography-mass spectrometry.
AB - Levels of urinary glucocorticoids and their concentration ratios have been
analyzed as potential markers for various pathological statuses. Large-scale
studies may possibly accelerate the investigations; however, a suitable method
needs to be established. Analytical conditions for measurement of urinary
glucocorticoids with LCMS were examined. Electrospray ionization in the positive
ion mode was applied for detection of cortisol (precursor>product ion:
363.3>121.0), cortisol-d4 (internal standard, IS, 367.4>121.1), and cortisone
(361.2>163.2). To maximize ionization, acetic acid-ammonium acetate buffer (18mM)
at pH 5.3 was employed as eluent A. A C18 column (100mm*2.1mm, 2.7MUm) at 50
degrees C was used for the 9.5min binary gradient separation starting with 60%
eluent A with methanol being eluent B. Linear correlations were observed between
the concentrations and the peak areas in the concentration range of 1-300ng/mL
with correlation coefficients (r) of 0.998 and 0.997 for cortisol and cortisone,
respectively, without IS adjustment, and 0.999 with IS adjustment for both
cortisol and cortisone. Solid-phase extraction (SPE) using a 2mL centrifuge
column was performed for the urine samples, with the original and final volumes
being 100MUL. The SPE of 12 urine specimens could be performed within 30min. The
effect of the sample matrix on the quantification of endogenous compounds present
in the urine extract was limited (coefficient of variation (CV) of IS-adjusted
matrix factor: 4.4-8.1%; urine extracts of 8 individuals); however, substantial
peak reduction of cortisol was observed at low concentrations. Exogenous
contaminants originating from the SPE centrifuge column seemed to be a main cause
for this phenomenon because the pure-water extract showed similar peak reduction.
A recovery of ~50% was obtained for both cortisol and cortisone. Adjustment with
the IS improved the apparent recovery, with ~100% being obtained for both
cortisol and cortisone. The recovery rate decreased when the urine samples were
concentrated in the SPE step; the reduction was greater for cortisol than for
cortisone. The lower limit of quantification (LLOQ) was set at 2.5ng/mL when the
injection volume was 10MUL, based on the reproducibility of the standards which
were measured (CV of 12 repetitions: 10.1% for 0.5ng/mL cortisol and 19.6% for
1ng/mL cortisone), the matrix effect (-55% at 2ng/mL concentrations of cortisol),
and the recovery rate (~50%). Furthermore an alternative approach for preparation
of the cortisol standards was required for low concentration range (2.5-20ng/mL)
because of the effect of the matrix. Degradation of original urine specimens at
room temperature was minimal during the first 24h. The extracted urine samples
degraded over time; however, their concentrations were corrected with the IS,
allowing for analysis up to 5days after extraction. In conclusion, an analytical
method for urinary glucocorticoids was established, which is fast, sensitive, and
well suited for practical application to large-scale study.
PMID- 28505490
TI - Heat induced temperature dysregulation and seizures in Dravet Syndrome/GEFS+
Gabrg2+/Q390X mice.
AB - It has been established that febrile seizures and its extended syndromes like
generalized epilepsy with febrile seizures (FS) plus (GEFS+) and Dravet syndrome
have been associated with mutations especially in SCN1A and GABRG2 genes. In
patients, the onset of FS is likely due to the combined effect of temperature and
inflammation in genetically vulnerable individuals because fever is often
associated with infection. Much effort has been spent to understand the
mechanisms underlying fever induction of seizures. In addition to the role of
cytokines in FS, previous studies in Scn1a+/- knockout mice, a model of Dravet
syndrome, indicated that temperature elevation alone could result in seizure
generation, and the effect of elevated temperature inducing seizures was age
dependent. Here, we report the thermal effect in a different mouse model of
Dravet syndrome, the Gabrg2+/Q390X knockin mouse. We demonstrated age-dependent
dysregulated temperature control and that temperature elevation produced
myoclonic jerks, generalized tonic clonic seizures (GTCSs) and heightened anxiety
like symptoms in Gabrg2+/Q390X mice. The study indicated that regardless of other
inflammatory factors, brief heat alone increased brain excitability and induced
multiple types of seizures in Gabrg2+/Q390X mice, suggesting that mutations like
GABRG2(Q390X) may alter brain thermal regulation and precipitate seizures during
temperature elevations.
PMID- 28505492
TI - Comprehensive evaluation of SCFA production in the intestinal bacteria regulated
by berberine using gas-chromatography combined with polymerase chain reaction.
AB - Short-chain fatty acids (SCFAs) of intestine microbial have caught accumulating
attention for their beneficial effects on human health. Botanic compounds with
low bioavailability such as berberine (BBR) and resveratrol might interact with
intestinal microbial ecosystem and promote gut bacteria to produce SCFA, which
contribute to their biological effects. In the present study, a comprehensive
assay system was built to detect SCFAs production in intestinal bacteria, in
which stringent anaerobic culture was applied for in vitro bacterial
fermentation, followed by direct-injection GC detection (chemical detection) in
combination with real time polymerase chain reaction (RT-PCR, biological
detection). BBR was used as positive reference. The direct injection GC method
was calibrated and successfully applied to analyze the concentration of SCFAs in
gut microbiota and BBR was proved to be effective in the dose- and time-dependent
up-regulation of SCFAs production. As compared to the saline group, the
concentration of acetic acid, propionate acid and butyric acid (the main SCFAs in
gut microbiota) were increased by 17.7%, 11.1% and 30.5%, respectively, after
incubating intestinal bacteria with 20MUg/mL BBR for 24h. The increase reached to
34.9%, 22.4% and 51.6%, respectively when the BBR was 50MUg/mL. Additionally,
consensus-degenerate hybrid oligonucleotide primers (CODEHOPs) were designed for
the detection of acetate kinase (ACK), Methylmalonyl-CoA decarboxylase (MMD) and
butyryl-CoA: acetate-CoA transferase (BUT), as they are the key enzymes in the
synthetic pathway for acetic acid, propionate acid and butyric acid,
respectively. After 24hr's incubation, BBR was shown to promote the gene
expression of ACK, MMD and BUT significantly (86.5%, 27.2% and 60.4%,
respectively, with 20MUg/mL BBR; 130.2%, 84.2% and 98.4%, respectively, with
50MUg/mL BBR), showing a solid biological support for the chemical detection.
This comprehensive assay system might be useful in identifying SCFAs promoting
agents with information on their mechanism.
PMID- 28505493
TI - Development of an analysis method for determination of sulfonamides and their
five acetylated metabolites in baby foods by ultra-high performance liquid
chromatography coupled to high-resolution mass spectrometry (Orbitrap-MS).
AB - A high sensitive and reliable multiresidue method was developed and validated for
determination of twelve sulfonamides and five acetylated metabolites in baby
foods by using UHPLC-Orbitrap-MS. The sample preparation included two extraction
methods as QuEChERS and ASE. The original QuEChERS method was performed, whereas
ASE method was optimized to achieve the best recovery for all analytes. UHPLC
Orbitrap-MS parameters were optimized to obtain good retention and separation in
LC and high sensitivity and selectivity in MS. The performance of the method was
evaluated according to the European Commision Decision 2002/657/EC. Matrix
matched calibration curves showed good r2 (>=0.999) and LOQ was ranged from 0.10
to 0.55MUg/kg. ASE was significantly more effective for extraction of the
analytes (recovery ranged from 75.5 to 96.6% with RSD<=10.1%) than QuEChERS
(recovery ranged from 60.9 to 85.9% with RSD<=19.1%). This method was applied to
the analysis of 47 different baby foods and no positive samples were found.
PMID- 28505494
TI - Melatonin protects mice against stress-induced inflammation through enhancement
of M2 macrophage polarization.
AB - Stress is known to cause neuropsychiatric diseases, and it has a detrimental
impact on the function of the immune system. Melatonin (MLT), a pineal gland
hormone, exhibits potent anti-inflammatory properties and it plays a fundamental
role in neuroimmunomodulation. In the present study, we investigated the
molecular mechanisms of MLT in stress-induced inflammation, focusing on
macrophage polarization. MLT (50 and 100mg/kg) or a vehicle control (5% ethanol
in saline) was intraperitoneally administered to mice once a day for 5days. After
the last treatment, mice were subjected to restraint stress (RS) for 2h. MLT
markedly decreased serum levels of corticosterone after RS. RS significantly
increased serum interleukin (IL)-1beta and IL-6 levels, and it decreased serum IL
10 levels. MLT administration attenuated these changes. After RS, MLT markedly
decreased lipid peroxidation and increased hepatic glutathione content. In
purified Kupffer cells (KCs) and peritoneal macrophages from mice exposed to RS,
the expression levels of M1 marker genes (NOS2a and CD40) increased, while the
expression levels of an M2 marker gene (Arg1) decreased. MLT attenuated this
increase in expression of M1 marker genes and decrease in the expression levels
of the M2 marker gene. Furthermore, in KCs and peritoneal macrophages exposed to
RS, MLT decreased the number of F4/80+CD86+ cells and increased the number of
F4/80+MRC1+ cells. In splenocytes exposed to RS, MLT inhibited the increase in
mRNA expression of NOS2a. MLT downregulated expression of phosphorylated signal
transducer and activator of transcription (STAT) 1 and upregulated STAT3 protein
expression. Our findings suggest that MLT reduces stress-induced inflammatory
responses by inducing an M1 to M2 phenotype switch in macrophages via activation
of STAT3 signaling.
PMID- 28505495
TI - Generalized Boussinesq-Scriven surface fluid model with curvature dissipation for
liquid surfaces and membranes.
AB - Curvature dissipation is relevant in synthetic and biological processes, from
fluctuations in semi-flexible polymer solutions, to buckling of liquid columns,
tomembrane cell wall functioning. We present a micromechanical model of curvature
dissipation relevant to fluid membranes and liquid surfaces based on a parallel
surface parameterization and a stress constitutive equation appropriate for
anisotropic fluids and fluid membranes.The derived model, aimed at high curvature
and high rate of change of curvature in liquid surfaces and membranes, introduces
additional viscous modes not included in the widely used 2D Boussinesq-Scriven
rheological constitutive equation for surface fluids.The kinematic tensors that
emerge from theparallel surface parameterization are the interfacial rate of
deformation and the surface co-rotational Zaremba-Jaumann derivative of the
curvature, which are used to classify all possibledissipative planar and non
planar modes. The curvature dissipation function that accounts for bending,
torsion and twist rates is derived and analyzed under several constraints,
including the important inextensional bending mode.A representative application
of the curvature dissipation model to the periodic oscillation in nano-wrinkled
outer hair cells show how and why curvature dissipation decreases with frequency,
and why the 100kHz frequency range is selected. These results contribute to
characterize curvature dissipation in membranes and liquid surfaces.
PMID- 28505496
TI - Inactivation of Gram (-) bacteria Salmonella enterica by chlorophyllin-based
photosensitization: Mechanism of action and new strategies to enhance the
inactivation efficiency.
AB - This study is focused on the enhancement of susceptibility of Gram (-) bacteria
S. enterica to chlorophyllin-based (Chl) photosensitization combining it with
other antimicrobial tools. In order to find best combinations, the mechanism by
which Chl-based photosensitization inactivates bacteria must be identified. Data
confirmed that photosensitization (Chl 1.5*10-5M, for 1-120min, 405nm, 0
46.1J/cm2) reduced S. enterica population, just by 2.05 log (CFU/ml).
Fluorimetric measurements indicated that just minor part of Chl was bound to
Salmonella in suspension. Addition of sodium azide (NaN3) (10mM) protected
bacteria from killing, what means that 1O2 took place in photochemical reactions.
Gene expression data confirmed that Chl-based photosensitization induced
oxidative stress in bacteria cells, since mostly genes responsible for
detoxification of ROS (OxyR, AhpC, GrxA) have been expressed in Salmonella.
Moreover, the expression of genes, responsible for the inhibition of oxidative
respiration (AtpC), cell division and down-regulation of metabolism (SulA) have
been detected. In addition, Chl-based photosensitization induced significant
release of intracellular components (absorbing at lambda260 nm and lambda280 nm)
in bacteria that indicated increased membrane permeability. Thus, the combination
of two antimicrobials (Chl-based photosensitization and chitosan (CHS)) with the
same target (cellular membrane) in the presence of light drastically reduced
viable Salmonella population (by 7.28 log). Combined treatment of
photosensitization and high power pulsed UV light (HPPL) was also very effective,
since reduced viable Salmonella by 7.5 log. Bacterial regrowth experiments
clearly indicated that after both combined treatments Salmonella lost its ability
to proliferate, and SEM images confirmed that after both treatments no viable
bacteria have been found at all.
PMID- 28505497
TI - Binding of ciprofloxacin to bovine serum albumin: Photophysical and thermodynamic
aspects.
AB - The present work reveals the study of interaction of a promising chemotherapeutic
drug ciprofloxacin (CFX) with a model transport protein bovine serum albumin
(BSA). The occurrence of the drug-protein interaction is found to result in
significant modulations of the fluorescence excitation and emission spectroscopic
properties of CFX following interaction with BSA. However, the major focus of the
study underlies a critical insight into the quantitation of the drug-protein
interaction phenomenon. To this end, we have exploited the isothermal titration
calorimetric (ITC) technique to quantify the affinity constant (Ka) and
stoichiometry (n) of the CFX-BSA interaction with simultaneous revelation of the
accompanying thermodynamics of the interaction process. In this context, our
discussion also sheds light on the lacuna surrounding various experimental
methodologies for evaluation of drug-protein binding parameters. Our endeavor
also extends to elucidation of the kinetic parameters and energy of activation
(Ea) of the CFX-BSA interaction. The present study also delineates the modulation
of the dynamical aspects of CFX following interaction with BSA. The rotational
relaxation dynamics of the protein-bound drug reveals the not-so-common "dip-rise
dip" anisotropy decay. Furthermore, the effect of drug binding on the native
protein conformation has been evaluated from circular dichroism (CD) spectroscopy
which reveals partial rupture of the protein secondary structure.
PMID- 28505498
TI - Ameliorative effects of rutin on hepatic encephalopathy-induced by thioacetamide
or gamma irradiation.
AB - Hepatic encephalopathy (HE) is a syndrome resulting from acute or chronic liver
failure. This study was designed to evaluate the effect of rutin on thioacetamide
(TAA) or gamma-radiation-induced HE model. Animals were received with TAA
(200mg/kg, i.p.) twice weekly for four weeks or exposed to 6Gy of gamma-radiation
to induce HE then groups orally treated with rutin (50mg/kg b.wt.) for four
weeks. At the end of experiment, blood, liver and brain samples were collected to
assess biochemical and biophysical markers as well histopathological
investigations. TAA or gamma-radiation exposed rats experienced increases in
serum activities of ALT, AST, ALP and ammonia level. Also an alteration in
relative permeability and conductivity of erythrocytes was observed. Furthermore,
cytokines levels and AChE activity were induced whereas the activities of HO-1
and neurotransmitters contents were depleted. TAA or gamma-radiation caused
distortion of hepatic and brain architecture as shown by histopathological
examination. Treatment with rutin resulted in improvement in liver function by
the decline in serum AST and ALT activities and reduction in serum ammonia level.
In addition, the administration of rutin significantly modulated the alteration
in cytokines levels and neurotransmitters content. Histopathological examinations
of liver and brain tissues showed that administration of rutin has attenuate TAA
or radiation-induced damage and improve tissue architecture. Consequently, rutin
has been a powerful hepatoprotective effect to combat hepatic encephalopathy
associated hyperammonemia and its consequential damage in liver and brain.
PMID- 28505499
TI - Clinical predictors of acute response to transcranial direct current stimulation
(tDCS) in major depression.
AB - BACKGROUND: Transcranial direct current stimulation (tDCS) is a promising
neuromodulation intervention for poor-responding or refractory depressed
patients. However, little is known about predictors of response to this therapy.
The present study aimed to analyze clinical predictors of response to tDCS in
depressed patients. METHODS: Clinical data from 3 independent tDCS trials on 171
depressed patients (including unipolar and bipolar depression), were pooled and
analyzed to assess predictors of response. Depression severity and the underlying
clinical dimensions were measured using the Hamilton Depression Rating Scale
(HDRS) at baseline and after the tDCS treatment. Age, gender and diagnosis
(bipolar/unipolar depression) were also investigated as predictors of response.
Linear mixed models were fitted in order to ascertain which HDRS factors were
associated with response to tDCS. RESULTS: Age, gender and diagnosis did not show
any association with response to treatment. The reduction in HDRS scores after
tDCS was strongly associated with the baseline values of "Cognitive Disturbances"
and "Retardation" factors, whilst the "Anxiety/Somatization" factor showed a mild
association with the response. LIMITATIONS: Open-label design, the lack of
control group, and minor differences in stimulation protocols. CONCLUSIONS: No
differences in response to tDCS were found between unipolar and bipolar patients,
suggesting that tDCS is effective for both conditions. "Cognitive disturbance",
"Retardation", and "Anxiety/Somatization", were identified as potential clinical
predictors of response to tDCS. These findings point to the pre-selection of the
potential responders to tDCS, therefore optimizing the clinical use of this
technique and the overall cost-effectiveness of the psychiatric intervention for
depressed patients.
PMID- 28505500
TI - Increase in the prescription rate of antidepressants after the Sewol Ferry
disaster in Ansan, South Korea.
AB - BACKGROUND: Previous pharmaco-epidemiological studies have reported increases in
the prescription of psychotropic medications after a disaster, reflecting post
disaster changes in psychiatric conditions and mental health service utilization.
We investigated changes in the prescription of psychotropic medications in the
Danwon district of Ansan city (Ansan Danwon) compared to a control community
before and after the Sewol Ferry disaster on April 16, 2014. METHODS: Data was
collected from the Korean Health Insurance Review and Assessment Service
database. We analyzed the prescription rates of psychotropic medications
including antidepressants, anxiolytics, and sedatives/hypnotics, and investigated
whether the time-series pattern of monthly prescriptions per 100,000 people was
different in Ansan Danwon compared to that in Cheonan city after the Sewol Ferry
disaster through difference-in-differences regression analysis. RESULTS: Ansan
Danwon showed a significantly greater increase (5.6%) in the prescription rate of
antidepressants compared to Cheonan city following the Sewol Ferry disaster.
There were no significant differences in changes in the prescription rates of
anxiolytics or sedatives/hypnotics. In the secondary analysis, a significantly
greater increase in the prescription rate of antipsychotics was observed in Ansan
Danwon compared to a control community after the disaster. LIMITATIONS: We could
not exclude the possibility that other events influenced changes in the
prescription rates of psychotropic medications during the study period.
CONCLUSIONS: Pharmaco-epidemiological studies on psychotropic medication
prescription after a disaster provide important information about population
level mental health. Our results suggest that the Sewol Ferry disaster exerted a
harmful effect on the mental health status of the affected community.
PMID- 28505501
TI - Cognitive-affective depression and somatic symptoms clusters are differentially
associated with maternal parenting and coparenting.
AB - BACKGROUND: Both depressive and somatic symptoms are significant predictors of
parenting and coparenting problems. However, despite clear evidence of their co
occurrence, no study to date has examined the association between depressive
somatic symptoms clusters and parenting and coparenting. The current research
sought to identify and cross-validate clusters of cognitive-affective depressive
symptoms and nonspecific somatic symptoms, as well as to test whether clusters
would differ on parenting and coparenting problems across three independent
samples of mothers. METHOD: Participants in Studies 1 and 3 consisted of 409 and
652 community mothers, respectively. Participants in Study 2 consisted of 162
mothers exposed to intimate partner violence. All participants prospectively
completed self-report measures of depressive and nonspecific somatic symptoms and
parenting (Studies 1 and 2) or coparenting (Study 3). RESULTS: Across studies,
three depression-somatic symptoms clusters were identified: no symptoms, high
depression and low nonspecific somatic symptoms, and high depression and
nonspecific somatic symptoms. The high depression-somatic symptoms cluster was
associated with the highest levels of child physical maltreatment risk (Study 1)
and overt-conflict coparenting (Study 3). No differences in perceived maternal
competence (Study 2) and cooperative and undermining coparenting (Study 3) were
found between the high depression and low somatic symptoms cluster and the high
depression-somatic symptoms cluster. CONCLUSIONS: The results provide novel
evidence for the strong associations between clusters of depression and
nonspecific somatic symptoms and specific parenting and coparenting problems.
Cluster stability across three independent samples suggest that they may be
generalizable. The results inform preventive approaches and evidence-based
psychotherapeutic treatments.
PMID- 28505502
TI - Sleep in the northern fur seal.
AB - The pattern of sleep in the fur seal, a semiaquatic pinniped, has several
striking behavioral and physiological adaptations that allow this species to
inhabit both the land and water environment. These features include
unihemispheric slow wave sleep (USWS, also being unihemispheric waking), the
ability to maintain movement for stabilization of the sleep posture and to
briefly open one eye while having a sleep electroencephalogram (EEG) in one
hemisphere. In vivo microdialysis studies suggest that acetylcholine release is
required for cortical activation during USWS, and that monoamines are not
required for USWS. The need to breathe, to maintain efficient thermoregulation,
and to avoid predation have shaped the sleep patterns in semiaquatic fur seals as
in fully aquatic cetaceans.
PMID- 28505503
TI - Intracranial neurenteric cyst mimicking an ependymoma: imaging features,
pathologic correlation and review of literature.
AB - We present a case of a 57-year-old female with four-months of diplopia and
vertigo. MRI revealed a mixed cystic and solid partially enhancing lesion of the
4th ventricle, foramen of Luschka and cerebellopontine angle. Preoperative
differential diagnosis favored ependymoma. Biopsy revealed a neurenteric cyst, a
benign developmental lesion that rarely occurs intracranially. This case
highlights several atypical manifestations of intracranial neurenteric cyst, with
regions of histologically benign solid enhancement, multicompartmental extra
axial location mimicking an ependymoma, and rapid recurrence without evidence of
underlying malignancy.
PMID- 28505505
TI - Measuring listening-related effort and fatigue in school-aged children using
pupillometry.
AB - Stress and fatigue from effortful listening may compromise well-being, learning,
and academic achievement in school-aged children. The aim of this study was to
investigate the effect of a signal-to-noise ratio (SNR) typical of those in
school classrooms on listening effort (behavioral and pupillometric) and
listening-related fatigue (self-report and pupillometric) in a group of school
aged children. A sample of 41 normal-hearing children aged 8-11years performed a
narrative speech-picture verification task in a condition with recommended levels
of background noise ("ideal": +15dB SNR) and a condition with typical classroom
background noise levels ("typical": -2dB SNR). Participants showed increased task
evoked pupil dilation in the typical listening condition compared with the ideal
listening condition, consistent with an increase in listening effort. No
differences were found between listening conditions in terms of performance
accuracy and response time on the behavioral task. Similarly, no differences were
found between listening conditions in self-report and pupillometric markers of
listening-related fatigue. This is the first study to (a) examine listening
related fatigue in children using pupillometry and (b) demonstrate physiological
evidence consistent with increased listening effort while listening to spoken
narratives despite ceiling-level task performance accuracy. Understanding the
physiological mechanisms that underpin listening-related effort and fatigue could
inform intervention strategies and ultimately mitigate listening difficulties in
children.
PMID- 28505506
TI - A methodology for efficiency optimization of betavoltaic cell design using an
isotropic planar source having an energy dependent beta particle distribution.
AB - Nuclear batteries based on silicon carbide betavoltaic cells have been studied
extensively in the literature. This paper describes an analysis of design
parameters, which can be applied to a variety of materials, but is specific to
silicon carbide. In order to optimize the interface between a beta source and
silicon carbide p-n junction, it is important to account for the specific
isotope, angular distribution of the beta particles from the source, the energy
distribution of the source as well as the geometrical aspects of the interface
between the source and the transducer. In this work, both the angular
distribution and energy distribution of the beta particles are modeled using a
thin planar beta source (e.g., H-3, Ni-63, S-35, Pm-147, Sr-90, and Y-90) with
GEANT4. Previous studies of betavoltaics with various source isotopes have shown
that Monte Carlo based codes such as MCNPX, GEANT4 and Penelope generate similar
results. GEANT4 is chosen because it has important strengths for the treatment of
electron energies below one keV and it is widely available. The model
demonstrates the effects of angular distribution, the maximum energy of the beta
particle and energy distribution of the beta source on the betavoltaic and it is
useful in determining the spatial profile of the power deposition in the cell.
PMID- 28505504
TI - Standardization of the apparent diffusion coefficient value of bladder cancer
across different centers: Applicability in predicting aggressive pathologic
phenotypes.
AB - PURPOSE: We investigated whether the standardized apparent diffusion coefficient
(ADC) value reflects bladder cancer characteristics across different centers.
METHODS: Ninety-eight bladder cancer patients underwent MRI at two institutions.
Standardized tumor ADC (sT-ADC) was calculated by dividing absolute tumor ADC (aT
ADC) by that of gluteus maximus. We compared ADCs between MRI protocols according
to grade and T-stage. RESULTS: The differences in aT-ADC between MRI protocols
were negated by sT-ADC. The best sT-ADC cut-offs to predict cancer aggressiveness
in the development cohort worked in the validation cohort compared to the
development cohort. CONCLUSION: Standardized ADC overcomes the incompatibility
between different MRI protocols.
PMID- 28505507
TI - The effect of pH and heat treatments on the foaming properties of purified alpha
lactalbumin from camel milk.
AB - The effect of pH (4.3 or 6.5) and heat treatment (70 degrees C or 90 degrees C
for 30min) on the foaming and interfacial properties of alpha-lactalbumin
extracted from camel milk were studied. The increased temperature treatment
changed the foaming properties of camel alpha-lactalbumin solution and its
ability to unfold at the air-water interface. At neutral pH, heat treatment was
found to improve foamability, whereas at acid pH (4.3) this property decreased.
Foams were more stable after a heat treatment at pH 4.3 than at 6.5, due to
higher levels of protein aggregation at low pH. Heat treatment at 90 degrees C
for 30min affected the physicochemical properties of the camel alpha-lactalbumin
by increasing free thiol group concentration at pH 6.5. Heat treatment also
caused changes in alpha-lactalbumin's surface charge. These results also confirm
the pronounced aggregation of heated camel alpha-lactalbumin solution at acid pH.
PMID- 28505508
TI - Phosphatase activities of a microepiphytic community during a bloom of Ostreopsis
cf. ovata in the northern Adriatic Sea.
AB - It is becoming more apparent that increased organic nutrient loads deriving from
anthropogenic activities and natural processes frequently cause the
eutrophication of coastal waters. Concurrently, an increasing number of
phototrophs have been shown to make use of organic nutrients, mainly through
indirect studies of surface enzyme activities or through direct studies of growth
in media containing organic-only nutrients. The potential utilization of
dissolved organic phosphorus (DOP) by microepiphytic-mats associated with
frequently problematic, toxic dinoflagellate Ostreopsis cf. ovata, was
investigated throughout a full cycle of a bloom that occurs annually (over the
last few decades) during summer along several stretches of the Mediterranean
coast. Measurements of phosphomonoesterase (PMEase) and phosphodiesterase
(PDEase) activities of the epiphytic mats (including cells and exopolymeric
substances) and a range of chemico-physical parameters were made from late summer
to early autumn at a eutrophic site. Analyses of ambient nutrient fractions
revealed very high aquatic N:P values (TN:TP = 178 +/- 50), very low filterable
reactive P (FRP) concentrations (13 out 19 under the limits of detection) and DOP
concentrations that were on average 85% of the total dissolved P. We recorded a
rapid increase in PMEase and PDEase activities in the epiphytic microalgal
community that coincided with the onset of a proliferation of the Ostreopsis
population. Chromogenic staining of samples showed that activity was closely
associated with the Ostreopsis cells, located both extracellularly (cell surface
and within the EPS) and intracellularly (ventral cytoplasm). The increase in both
phosphatases indicates that Ostreopsis can utilise a wide range of DOP types. The
intense activity in the EPS was suggested to aid in the efficient entrapment and
processing of high concentration nutrient pulses, for extracellular processing of
larger organic materials and to prevent loss of substrates and products to the
surrounding water. Based on the present findings, Ostreopsis seems to have
adaptations that allow it to thrive in P-limited environments where organic P is
the main source of P.
PMID- 28505509
TI - Fungal biocatalyst activated by an electric field: Improved mass transfer and non
specificity for hydrocarbon degradation in an airlift bioreactor.
AB - The combination of biological and electrochemical techniques enhances the
bioremediation efficiency of treating oil-contaminated water. In this study a non
growing fungal whole cell biocatalyst (BC; Aspergillus brasiliensis attached to
perlite) pretreated with an electric field (EF), was used to degrade a
hydrocarbon blend (hexadecane-phenanthrene-pyrene; 100:1:1w/w) in an airlift
bioreactor (ALB). During hydrocarbon degradation, all mass transfer resistances
(internal and external) and sorption capacity were experimentally quantified.
Internal mass transfer resistances were evaluated through BC effectiveness factor
analysis as a function of the Thiele modulus (using first order reaction
kinetics, assuming a spherical BC, five particle diameters). External
(interfacial) mass transfer resistances were evaluated by kLa determination. EF
pretreatment during BC production promoted surface changes in BC and production
of an emulsifier protein in the ALB. The BC surface modifications enhanced the
affinity for hydrocarbons, improving hydrocarbon uptake by direct contact. The
resulting emulsion was associated with decreased internal and external mass
transfer resistances. EF pretreatment effects can be summarized as: a combined
uptake mechanism (direct contact dominant followed by emulsified form dominant)
diminishing mass transfer limitations, resulting in a non-specific hydrocarbon
degradation in blend. The pretreated BC is a good applicant for oil-contaminated
water remediation.
PMID- 28505510
TI - A potential mechanism for degradation of 4,5-dichloro-2-(n-octyl)-3[2H]
isothiazolone (DCOIT) by brown-rot fungus Gloeophyllum trabeum.
AB - This study aims to investigate the biodegradation of 4,5-dichloro-2-(n-octyl)
3[2H]-isothiazolone (DCOIT) by a brown-rot fungus Gloeophyllum trabeum as well as
the involved mechanism. In the present study, the retentions of DCOIT in treated
Masson pine (Pinus massoniana) (MP) chips were determined periodically after
incubation with G. trabeum. Then a Fenton-like reaction, known as the chelator
mediated Fenton (CMF) chemistry was used to degrade DCOIT that mimics the
degradation pathway of DCOIT by typical brown-rot fungi, and the degradation
intermediates were further analyzed. The results demonstrated that DCOIT was
rapidly depleted in the early stages of incubation by G. trabeum. The CMF
treatment was shown to oxidatively decompose DCOIT by producing reactive oxygen
species. This evidence suggests that the CMF chemistry employed by brown-rot
fungi contributes to the rapid depletion of DCOIT during G. trabeum exposure,
although this does not rule out other possible mechanisms for the biodegradation
of DCOIT. The new findings give new insights into the mechanism for the
biodegradation of organic biocides, and potentially provide an efficient approach
for the removal of organic pollutants in the contaminated water.
PMID- 28505511
TI - Novel electrodialysis cation exchange membrane prepared by 2-acrylamido-2
methylpropane sulfonic acid; heavy metal ions removal.
AB - In the present work a novel heterogeneous cation exchange membrane (CEM) composed
of poly vinyl chloride (PVC) and 2-acrylamido-2-methylpropane sulfonic acid based
hydrogel (AMAH) was prepared. The membranes were fabricated with different
fractions of AMAH to optimize the performance in desalination. The hydrogel was
characterized by FT-IR to prove the successful synthesis. The membrane properties
such as permselectivity, ionic permeability, flux, water content, electrical
resistance, morphology, contact angle and dimensional stability were evaluated.
Modified membranes showed acceptable dimensional stabilities, more hydrophilic
surface, higher water content and porosity. SEM images revealed the formation of
a more porous membrane structure. Membrane permselectivity and transport number
showed a relatively constant then decreasing trend in Na+ and Ba2+ solutions. The
experimental results showed that the incorporation of AMAH into the PVC matrix
obviously improved ionic permeability and flux of Na (~9%) and Ba (~23%).
Membrane electrical resistance was declined about 36% by adding AMAH in the
membrane structure. Membranes' performance in potassium and heavy metal ions
removal showed a remarkable separation capacity of K+ (99.9%), Pb2+ (99.9%) and
Ni2+ (96.9%). Membranes showed desirable potential for scaling removal.
PMID- 28505512
TI - Identifying the impacts of climate on the regional transport of haze pollution
and inter-cities correspondence within the Yangtze River Delta.
AB - Regional haze pollution has become an important environmental issue in the
Yangtze River Delta (YRD) region. Regional transport and inter-influence of PM2.5
among cities occurs frequently as a result of the subtropical monsoon climate.
Backward trajectory statistics indicated that a north wind prevailed from October
to March, while a southeast wind predominated from May to September. The temporal
relationships of carbon and nitrogen isotopes among cities were dependent on the
prevailing wind direction. Regional PM2.5 pollution was confirmed in the YRD
region by means of significant correlations and similar cyclical characteristics
of PM2.5 among Lin'an, Ningbo, Nanjing and Shanghai. Granger causality tests of
the time series of PM2.5 values indicate that the regional transport of haze
pollutants is governed by prevailing wind direction, as the PM2.5 concentrations
from upwind area cities generally influence that of the downwind cities.
Furthermore, stronger correlation coefficients were identified according to
monsoon pathways. To clarify the impacts of the monsoon climate, a vector
autoregressive (VAR) model was introduced. Variance decomposition in the VAR
model also indicated that the upwind area cities contributed significantly to
PM2.5 in the downwind area cities. Finally, we attempted to predict daily PM2.5
concentrations in each city based on the VAR model using data from all cities and
obtained fairly reasonable predictions. These indicate that statistical methods
of the Granger causality test and VAR model have the potential to evaluate inter
influence and the relative contribution of PM2.5 among cities, and to predict
PM2.5 concentrations as well.
PMID- 28505513
TI - Polyfluoroalkyl substance exposure in the Mid-Ohio River Valley, 1991-2012.
AB - BACKGROUND: Industrial discharges of perfluorooctanoic acid (PFOA) to the Ohio
River, contaminating water systems near Parkersburg, WV, were previously
associated with nearby residents' serum PFOA concentrations above US general
population medians. Ohio River PFOA concentrations downstream are elevated,
suggesting Mid-Ohio River Valley residents are exposed through drinking water.
OBJECTIVES: Quantify PFOA and 10 other per- and polyfluoroalkyl substances (PFAS)
in Mid-Ohio River Valley resident sera collected between 1991 and 2013 and
determine whether the Ohio River and Ohio River Aquifer are exposure sources.
METHODS: We measured eleven PFAS in 1608 sera from 931 participants. Serum PFOA
concentration and water source associations were assessed using linear mixed
effects models. We estimated between-sample serum PFOA using one-compartment
pharmacokinetics for participants with multiple samples. RESULTS: In serum
samples collected as early as 1991, PFOA (median = 7.6 ng/mL) was detected in
99.9% of sera; 47% had concentrations greater than US population 95th
percentiles. Five other PFAS were detected in greater than 82% of samples; median
other PFAS concentrations were similar to the US general population. Serum PFOA
was significantly associated with water source, sampling year, age at sampling,
tap water consumption, pregnancy, gravidity and breastfeeding. Serum PFOA was 40
60% lower with granular activated carbon (GAC) use. Repeated measurements and
pharmacokinetics suggest serum PFOA peaked 2000-2006 for participants using water
without GAC treatment; where GAC was used, serum PFOA concentrations decreased
from 1991 to 2012. CONCLUSIONS: Mid-Ohio River Valley residents appear to have
PFOA, but not other PFAS, serum concentrations above US population levels.
Drinking water from the Ohio River and Ohio River Aquifer, primarily contaminated
by industrial discharges 209-666 km upstream, is likely the primary exposure
source. GAC treatment of drinking water mitigates, but does not eliminate, PFOA
exposure.
PMID- 28505514
TI - TLR4 supports the expansion of FasL+CD5+CD1dhi regulatory B cells, which
decreases in contact hypersensitivity.
AB - Certain B cells termed as "regulatory B cells" (Bregs) can suppress the ongoing
immune responses and a splenic CD5+CD1dhi Breg subset identified earlier was
shown to exert its regulatory functions through secretion of IL-10. Though FasL
expression is an alternative mechanism of immune suppression used by B cells,
little is known about the FasL expressing CD5+CD1dhi Bregs. In this study, we
isolated splenocytes or splenic CD19+ B cells and compared the efficiency of toll
like receptor(TLR)4 ligand (lipopolysaccharide) with TLR9 ligand (CpG), anti-CD40
and TLR9 ligand (CpG) plus anti-CD40 on the FasL expression of splenic CD5+CD1dhi
Bregs by flow cytometry. FasL expression in CD5+CD1dhi B cells was rapidly
increased after TLR4 ligation. Intriguingly, anti-CD40 and CpG plus anti-CD40
combinations failed to stimulate FasL expression in CD5+CD1dhi B cells although
the IL-10 production was up-regulated in this subset. In addition, LPS and other
B10-cell inducers increased the expression of surface molecules like CD86 and
CD25, which are correlated to the regulatory functions of B cells. Furthermore,
NF-kappaB and NF-AT inhibitors decreased the TLR4-activated FasL expression in
CD5+CD1dhi B cells. Then we sorted splenic CD5+CD1dhi Bregs using flow cytometry
and found that TLR4-activated CD5+CD1dhi Bregs suppressed the proliferation of
CFSE-labeled CD4+ T cells in vitro, which was partly blocked by anti-FasL
antibody. In oxazolone-sensitized mice having contact hypersensitivity, FasL
expression in splenic CD5+CD1dhi B cells was decreased compared to the control
group after TLR4 ligation. Our findings suggest that the regulatory function of
CD5+CD1dhi B cells could be partly mediated by Fas-FasL pathway and this FasL
expressing CD5+CD1dhi Bregs might participate in the regulation of inflammatory
diseases.
PMID- 28505515
TI - RhoB induces the production of proinflammatory cytokines in TLR-triggered
macrophages.
AB - Toll-like receptors (TLRs) are the primary sensors detecting conserved molecular
patterns on microorganisms, thus acting as important components of innate
immunity against invading pathogens. Many positive and negative regulators of TLR
triggered signaling have been identified. The Rho GTPase RhoB plays a key role in
cell migration, division and polarity; however, the function and regulatory
mechanisms of RhoB in TLR ligand-triggered innate immune responses remain to be
investigated. Here, we report that the expression of RhoB is induced by TLR
agonists (lipopolysaccharide (LPS), CpG, poly(I:C)) in macrophages. Knockdown of
RhoB expression markedly decreased TLR ligand-induced activation of mitogen
activated protein kinases and nuclear factor-kappaB (NF-kappaB), and the
production of tumor necrosis factor alpha (TNFalpha), interleukin (IL)-6 and IL
1beta in macrophages stimulated with TLR ligands. Furthermore, we demonstrated
that RhoB interacts with major histocompatibility complex class II (MHCII) alpha
chain, but not beta chain, in endosomes of macrophages. Knockdown of MHCII
expression greatly reduced the interaction of RhoB with Btk, and attenuated the
induction of NF-kappaB and interferon beta activity by RhoB upon LPS stimulation.
These findings suggest that RhoB is a positive physiological regulator of TLRs
signaling via binding to MHCII in macrophages, and therefore RhoB may be a
potential therapeutic target in inflammatory diseases.
PMID- 28505516
TI - Induction of experimental autoimmune orchitis by immunization with xenogenic
testicular germ cells in mice.
AB - We previously showed that immunization of mice with syngeneic or allogeneic
testicular germ cells (TGC) alone induces autoimmune inflammation in the testes
without using any adjuvant. In the present study, we examined testicular
autoimmune response against xenogenic TGC antigens in mice. The mice were
immunized with murine, rat or guinea pig TGC and then the histopathology, delayed
type hypersensitivity (DTH) response and humoral autoimmunity were investigated.
The results showed that immunization with not only murine but also rat TGC caused
experimental autoimmune orchitis (EAO) with hypospermatogenesis in mice, while
that with guinea pig TGC could not. The DTH response to murine TGC was
significantly elevated in mice that had been immunized with murine or rat but not
guinea pig TGC. Serum autoantibody to murine TGC was immunohistochemically
detected in the mice immunized with either murine, rat or guinea pig TGC,
however, the level of autoantibody detected by ELISA revealed significant
elevation when mice were immunized with murine and rat TGC. With the
immunoblotting after electrophoresis, the murine TGC proteins at molecular masses
around 55kDa and 70kDa can be detected when incubated with sera from m-TGC and r
TGC groups. These results represent the cross-reactivity among TGC of the mouse,
the rat and the guinea pig at the levels of humoral immunity and also demonstrate
that the rat TGC could elicit significant DTH response to murine TGC with the
resultant EAO. This is the first to succeed in EAO induction by the use of
xenogenic TGC.
PMID- 28505517
TI - A Modified Adenovirus Vector-Mediated Antibody Screening Method Identifies EphA2
as a Cancer Target.
AB - BACKGROUND: We constructed a genetically modified adenovirus vector incorporating
an IgG Fc-binding motif from staphylococcal protein A, Z33 (Adv-FZ33). Adv-FZ33
allows an antibody to redirect the vector to a target molecule on the cell
surface. We attempted to search for target antigen candidates and antibodies that
allowed highly selective gene transduction into malignant tumors. METHODS:
Hybridoma libraries producing monoclonal antibodies (mAbs) were screened that
increased transduction efficiency in cancer cell lines after cross-linking with
Adv-FZ33. Target antigens of the mAbs were identified by immunoprecipitation and
mass spectrometry. Of these mAbs, we noted a clone, F2-27, that recognized the
receptor tyrosine kinase EphA2. Next, we generated an adenovirus vector, Ax3CMTK
FZ33, that expressed a herpes simplex virus thymidine kinase (HSV-TK). The
therapeutic efficacy of F2-27-mediated HSV-TK gene transduction, followed by
ganciclovir (GCV) administration, was studied in vitro. The inhibitory effect of
F2-27 on cancer cell invasion was investigated by a three-dimensional spheroid
formation assay. RESULTS: In vitro reporter gene expression after Adv-FZ33
infection via F2-27 was 146 times higher than with control mAb in EphA2
expressing cancer cell lines. F2-27-mediated Ax3CMTK-FZ33 infection induced the
HSV-TK gene in an F2-27-dependent manner and had a highly effective cytotoxic
effect in a GCV-dependent manner. Additionally, F2-27 independently inhibited
migration of EphA2-positive breast cancer cell lines in three-dimensional
culture. CONCLUSION: Our modified adenovirus and hybridoma screening system is
useful for the development of targeted cancer therapy, and F2-27 has the
potential to be an antibody-based therapy for various EphA2-positive cancers.
PMID- 28505518
TI - Registered nurse buddies: Educators by proxy?
AB - The informal clinical teaching role of the buddy nurse seems to be a uniquely
Australian title, with little consistency in terminology for informal nurse
educator roles internationally. Not all registered nurses are professionally
developed for the informal role of facilitating the clinical learning of students
in clinical settings, yet these roles are expected by nursing professional
bodies. In Australia the registered nurses (RN) experience of being a buddy nurse
has been reported as lacking clarity, being unsupported and structureless. Whist
there is a plethora of literature published about formal RN educator roles,
little is available on the informal buddy nurse role. A view of the buddy nurse
role in reference to the limited but available literature in the Australian
context is offered in this paper. International perspectives are also gathered
describing informal clinical education RN's roles with similar responsibilities
to the Australian buddy nurse. The significance of this dialogue is to ignite
debate about the role, potentially informing policy for the improved support of
the role within the Australian nursing landscape.
PMID- 28505519
TI - Impact of interactive situated and simulated teaching program on novice nursing
practitioners' clinical competence, confidence, and stress.
AB - BACKGROUND: Novice nursing practitioners (NNPs) often struggle to make the
transition to fully competent professionals. We sought to determine the impact of
an interactive, situated learning workshop on a participant's clinical
competence. OBJECTIVES: This work aimed to improve the clinical competence,
promote the self-confidence, and reduce the number of work-related stressors of
NNPs. METHODS: We randomly allocated 31 newly graduated NNPs into interactive
situated and simulated teaching (ISST) and non-ISST groups, which were perceived
as the homogeneity of the 2 groups based upon no significant difference at age,
education level and work units. The ISST program comprised six follow-up
interactive face-to-face support sessions over a three-month period following the
standard orientation training course. We assessed the participants' competency,
stress, and confidence levels in professional competence before and at the end of
the study. RESULTS: At the end of the three-month study period, the ISST group
demonstrated superior nursing competency (p=0.001), as well as reported lower
stress levels (p=0.011), and increased confidence in professional competence
(p=0.026) as compared with those in the control group. A multiple regression
analysis revealed that clinical nursing competence was positively correlated with
the use of ISST (p=0.02) and negatively correlated with stress (p=0.03).
CONCLUSIONS: The ISST program for NNPs significantly improved their clinical
competence. It may be helpful to ensure that new trainees have access to training
programs that can facilitate their acclimation to their new working environments
at the beginning of their careers.
PMID- 28505520
TI - Nursing program evaluation for Nurse Educators.
PMID- 28505521
TI - Short simulation exercises to improve emergency department nurses' self-efficacy
for initial disaster management: Controlled before and after study.
AB - INTRODUCTION: Head nurses at emergency departments often assume responsibility
for managing the initial response to a major incident, and to create surge
capacity. Training is essential to enable these nurses to perform an effective
disaster response. Evaluating the effects of such training is however complicated
as real skill only can be demonstrated during a real major incident. Self
efficacy has been proposed as an alternative measure of training effectiveness.
PURPOSE: The aim of this study was to examine if short, small-scale computer
based simulation exercises could improve head emergency nurses' general and
specific self-efficacy and initial incident management skills. METHOD: A within
group pretest-posttest design was used to examine 13 head nurses' general and
specific self-efficacy before and after an intervention consisting of three short
computer based simulation exercises during a 1-h session. Management skills were
assessed using the computer simulation tool DigEmergo. RESULTS: The exercises
increased the head nurses' general self-efficacy but not their specific self
efficacy. After completing the first two exercises they also exhibited improved
management skills as indicated by shorter time to treatment for both trauma and
in-hospital patients. CONCLUSION: This study indicates that short computer based
simulation exercises provide opportunities for head nurses to improve management
skills and increase their general self-efficacy.
PMID- 28505522
TI - The Knowledge-about-Older-Patients - Quiz (KOP-Q) for nurses: Cross-cultural
validation between the Netherlands and United States of America.
AB - BACKGROUND: The Knowledge about Older Patients-Quiz (KOP-Q) is designed as a
unidimensional scale measuring knowledge of hospital nurses about older patients.
Furthermore, the KOP-Q measures a second unidimensional construct, certainty of
hospital nurses about their knowledge. The KOP-Q is developed and validated in
the Netherlands. Whether the KOP-Q can be used in other countries is unknown
given the cultural and language differences. OBJECTIVES: Investigate the level of
measurement invariance of the KOP-Q between the Netherlands and United States of
America (USA). DESIGN: A multicenter international cross-sectional design.
SETTINGS: Four general hospitals in the Netherlands and four general hospitals in
the USA. PARTICIPANTS: Nurses from the Netherlands (n=201) and the USA (n=130)
were invited to participate by email from the ward manager, distributing flyers
and present messages on the online hospital communication boards. Questions of
the KOP-Q were completed online. METHOD: The level of measurement invariance
(configural, metric or scalar invariance) across countries was tested by running
increasingly constrained structural equation models, and testing whether these
models fitted the data. RESULTS: Both the knowledge and certainty construct of
the KOP-Q proved unidimensional in the Netherlands and USA sample. Test results
of the measurement invariance across the Netherlands and USA indicated a stable,
partial scalar invariance (15 items full scalar invariance) for the knowledge
items and full scalar invariance for the certainty items. CONCLUSIONS: The KOP-Q
shows to function uniformly across both language groups and can therefore be used
to assess nurses' knowledge and their certainty about this knowledge which can be
important for educational and/or quality improvement programs in the USA.
Furthermore, the KOP-Q is suitable to make comparisons between the Netherlands
and the USA using latent variable models. Before the KOP-Q can be used in other
countries, cross-cultural tests should again be performed.
PMID- 28505523
TI - Trainers' perception of the learning environment and student competency: A
qualitative investigation of midwifery and anesthesia training programs in
Ethiopia.
AB - BACKGROUND: Ethiopia has successfully expanded training for midwives and
anesthetists in public institutions. This study explored the perceptions of
trainers (instructors, clinical lab assistants and preceptors) towards the
adequacy of students' learning experience and implications for achieving mastery
of core competencies. METHODS: In-depth interviews with 96 trainers at 9 public
universities and 17 regional health science colleges across Ethiopia were
conducted to elicit their opinions about available resources, program curriculum
suitability, and competence of graduating students. Using Dedoose, data were
thematically analyzed using grounded theory. RESULTS: Perceptions of anesthesia
and midwifery programs were similar. Common challenges included unpreparedness
and poor motivation of students, shortages of skills lab space and equipment,
difficulties ensuring students' exposure to sufficient and varied enough cases to
develop competence, and lack of coordination between academic training
institutions and clinical attachment sites. Additional logistical barriers
included lack of student transport to clinical sites. Informants recommended
improved recruitment strategies, curriculum adjustments, increased time in skills
labs, and better communication across academic and clinical sites. CONCLUSIONS:
An adequate learning environment ensures that graduating midwives and
anesthetists are competent to provide quality services. Minimizing the human
resource, infrastructural and logistical gaps identified in this study requires
continued, targeted investment in health systems strengthening.
PMID- 28505525
TI - Thrombin generation and intracranial atherosclerotic disease in patients with a
transient ischaemic attack.
AB - BACKGROUND: Intracranial atherosclerotic disease (ICAD) is responsible for at
least 10% of transient ischaemic attacks (TIA). Thrombin generation has been
shown to be associated with several atherosclerotic conditions and may be
relevant in the pathogenesis of TIA from ICAD. OBJECTIVE: To evaluate the
association between thrombin generation and ICAD in patients with TIA. MATERIALS
AND METHODS: Consecutive patients with confirmed diagnosis of TIA by vascular
neurologist were enrolled. Within 24h from diagnosis, all the patients underwent:
blood samples including thrombin generation search, electrocardiography, brain CT
scan, blood pressure (BP) measurement, supra-aortic echo-Doppler, transcranial
Doppler (TCD) and standard echocardiogram. Thrombin generation was measured as
endogenous thrombin potential (ETP) in platelet-rich plasma (PRP) and in platelet
poor plasma (PPP), in the presence and in the absence of thrombomodulin (TM).
RESULTS: 120 patients (male 52.5%), aged 69+/-16years were enrolled. Ten patients
on warfarin treatment had significantly lower ETP than the others. Among the
remaining, ETP in the presence or absence of TM did not differ according to TOAST
classification aetiology (large vessel vs. cardioembolic vs. lacunar vs. others).
In PRP, ETP was similar in patients with ICAD and in those without (1748+/-160
vs. 1851+/-36nM.min, p=0.393), whereas, ETP measured in presence of
thrombomodulin was higher in patients with than in those without ICAD (2045+/-99
vs. 1715+/-41nM.min, p=0.011). In PPP, ETP was similar in patients with ICAD and
in those without, whereas thrombin peak was higher in patients with ICAD than in
those without both in the presence (165+/-17 vs. 130+/-5nM, p=0.036) and in the
absence of TM (178+/-19 vs. 142+/-5nM, p=0.037). CONCLUSION: ETP measured in
presence of TM is enhanced in patients with ICAD, supporting that thrombomodulin
protein C pathways is relevant in TIA from ICAD. These hypothesis-generating data
suggest that thrombin generation may be relevant in cerebral ischaemia from
intracranial disease, and justify larger studies.
PMID- 28505526
TI - Peripheral hearing loss reduces the ability of children to direct selective
attention during multi-talker listening.
AB - Restoring normal hearing requires knowledge of how peripheral and central
auditory processes are affected by hearing loss. Previous research has focussed
primarily on peripheral changes following sensorineural hearing loss, whereas
consequences for central auditory processing have received less attention. We
examined the ability of hearing-impaired children to direct auditory attention to
a voice of interest (based on the talker's spatial location or gender) in the
presence of a common form of background noise: the voices of competing talkers
(i.e. during multi-talker, or "Cocktail Party" listening). We measured brain
activity using electro-encephalography (EEG) when children prepared to direct
attention to the spatial location or gender of an upcoming target talker who
spoke in a mixture of three talkers. Compared to normally-hearing children,
hearing-impaired children showed significantly less evidence of preparatory brain
activity when required to direct spatial attention. This finding is consistent
with the idea that hearing-impaired children have a reduced ability to prepare
spatial attention for an upcoming talker. Moreover, preparatory brain activity
was not restored when hearing-impaired children listened with their acoustic
hearing aids. An implication of these findings is that steps to improve auditory
attention alongside acoustic hearing aids may be required to improve the ability
of hearing-impaired children to understand speech in the presence of competing
talkers.
PMID- 28505527
TI - Amino acid and acetylcholine chemistry in the central auditory system of young,
middle-aged and old rats.
AB - Older adults generally experience difficulties with hearing. Age-related changes
in the chemistry of central auditory regions, especially the chemistry underlying
synaptic transmission between neurons, may be of particular relevance for hearing
changes. In this study, we used quantitative microchemical methods to map
concentrations of amino acids, including the major neurotransmitters of the
brain, in all the major central auditory structures of young (6 months), middle
aged (22 months), and old (33 months old) Fischer 344 x Brown Norway rats. In
addition, some amino acid measurements were made for vestibular nuclei, and
activities of choline acetyltransferase, the enzyme for acetylcholine synthesis,
were mapped in the superior olive and auditory cortex. In old, as compared to
young, rats, glutamate concentrations were lower throughout central auditory
regions. Aspartate and glycine concentrations were significantly lower in many
and GABA and taurine concentrations in some cochlear nucleus and superior olive
regions. Glutamine concentrations and choline acetyltransferase activities were
higher in most auditory cortex layers of old rats as compared to young. Where
there were differences between young and old rats, amino acid concentrations in
middle-aged rats often lay between those in young and old rats, suggesting
gradual changes during adult life. The results suggest that hearing deficits in
older adults may relate to decreases in excitatory (glutamate) as well as
inhibitory (glycine and GABA) neurotransmitter amino acid functions. Chemical
changes measured in aged rats often differed from changes measured after
manipulations that directly damage the cochlea, suggesting that chemical changes
during aging may not all be secondary to cochlear damage.
PMID- 28505524
TI - Inactivated influenza virus vaccines: the future of TIV and QIV.
AB - Influenza viruses continue to be a major public health concern, despite the
availability of vaccines. Currently licensed influenza vaccines aim at the
induction of antibodies that target hemagglutinin, the major antigenic
determinant on the surface of influenza virions that is responsible for
attachment of the virus to the host cell that is to be infected. Currently
licensed influenza vaccines come as inactivated or live attenuated influenza
vaccines and are trivalent or quadrivalent as they contain antigens of two
influenza A and one or two influenza B strains that circulate in the human
population, respectively. In this review we briefly compare trivalent and
quadrivalent inactivated influenza vaccines (TIV and QIV) with live attenuated
influenza vaccines (LAIV). The use of the latter vaccine type in children age 2-8
has been disrecommended recently by the American Centers for Disease Control and
Prevention due to inferior vaccine effectiveness in this age group in recent
seasons. This recommendation will favor the use of TIV and QIV over LAIV in the
near future. However, there is much evidence from studies in humans that
illustrate the benefit of LAIV and we discuss some of the mechanisms that
contribute to broader protection against influenza viruses of different subtypes
induced by natural infection and LAIV. The future challenge will be to apply
these insights to allow induction of broader and long-lasting protection provided
by TIV and QIV vaccines, for example, by the use of adjuvants or combining LAIV
with TIV and QIV. Other immune factors than serum hemagglutination inhibiting
antibodies have shown to correlate with protection provided by TIV and QIV, which
illustrates the need for other correlates of protection than hemagglutination
inhibition by serum antibodies and justifies more focus on influenza antigens in
the TIV and QIV other than hemagglutinin.
PMID- 28505528
TI - Acuity in ranging based on delay-tuned combination-sensitive neurons in the
auditory cortex of mustached bats.
AB - A 1.0-ms echo delay from an emitted bio-sonar pulse at 25 degrees C corresponds
to a 17.3-cm target distance. In the auditory cortex of the mustached bat,
Pteronotus parnellii, neurons tuned to a specific delay (best delay) of an echo
from an emitted pulse are clustered in the FF, dorsal fringe and ventral fringe
areas. ("FF" stands for the frequency-modulated components of a pulse and its
echo.) Those delay-tuned neurons are systematically arranged in the FF area
according to their best delays and form a 18-ms-long delay axis. Using the
neurophysiological data, the theoretical acuity at a 75% correct level was
computed as just-noticeable changes in (a) the location of maximally responding
delay-tuned neurons, (b) the location of the center of all responses in the FF
area, and (c) the weighted sum of responses of all delay-tuned neurons. The
acuity is range-dependent: the shorter the target range, the higher the acuity
is. The just-noticeable changes in target range are 7.57-46.2, 0.50-2.32 and 0.22
2.53 mm at the target ranges of up to 140 cm for (a), (b) and (c), respectively.
When the dorsal and ventral fringe areas are included in the computation, the
just-noticeable changes become smaller than those in the FF area alone. Those
acuities computed are comparable to certain behavioral acuities.
PMID- 28505529
TI - Influence of Bisphenol A on the transport and deposition behaviors of bacteria in
quartz sand.
AB - The influence of Bisphenol A (BPA) on the transport and deposition behaviors of
bacteria in quartz sand was examined in both NaCl (10 and 25 mM) and CaCl2
solutions (1.2 and 5 mM) by comparing the breakthrough curves and retained
profiles of cell with BPA in suspensions versus those without BPA. Gram-negative
Escherichia coli and Gram-positive Bacillus subtilis were employed as model cells
in the present study. The extended Derjaguin-Landau-Verwey-Overbeek interaction
energy calculation revealed that the presence of BPA in cell suspensions led to a
lower repulsive interaction between the cells and the quartz sand. This suggests
that, theoretically, increased cell deposition on quartz sand would be expected
in the presence of BPA. However, under all examined solution conditions, the
presence of BPA in cell suspensions increased transport and decreased deposition
of bacteria in porous media regardless of cell type, ionic strength, ion valence,
the presence or absence of extracellular polymeric substances. We found that
competition by BPA through hydrophobicity for deposition sites on the quartz sand
surfaces was the sole contributor to the enhanced transport and decreased
deposition of bacteria in the presence of BPA.
PMID- 28505530
TI - Photocatalytic wastewater purification with simultaneous hydrogen production
using MoS2 QD-decorated hierarchical assembly of ZnIn2S4 on reduced graphene
oxide photocatalyst.
AB - It is attractive to photocatalytically purify wastewater and simultaneously
convert solar energy into clean hydrogen energy. However, it is still a challenge
owing to the relatively low photocatalytic efficiency of photocatalysts. In this
study, we synthesized a molybdenum disulfide (MoS2) quantum dot-decorated 3D
nanoarchitecture (MoS2QDs) of indium zinc sulfide (ZnIn2S4) and reduced grapheme
oxide (MoS2QDs@ZnIn2S4@RGO) photocatalyst using a simple solvothermal method. The
RGO promotes the electron transfer, and the highly dispersed MoS2QDs provides
numerous catalytic sites. The photocatalytic purification of rhodamine B (RhB),
eosin Y (EY), fulvic acid (FA), methylene blue (MB) and p-nitrophenol (PNP) in
simulated wastewaters were further tested. The degradation efficiencies and TOC
removal were 91% and 75% for PNP, 92.2% and 72% for FA, 98.5% and 80% for MB,
98.6% and 84% for EY, and 98.8% and 88% for RhB, respectively (Corganics = 20
mg/L, Ccatalyst = 1.25 g/L, t = 12 h, Ilight = 3.36 * 10-5 E L-1 s-1). Among
these tests, the highest hydrogen production was achieved (45 MUmol) during RhB
degradation. Both experimental and calculational results prove that lower LUMO
(lowest unoccupied molecular orbit) level of organic molecules was available for
transferring electrons to catalysts, resulting in more efficient hydrogen
production. Significantly, the removal efficiencies of natural organic substances
in actual river water reached 76.3-98.4%, and COD reduced from 32 to 16 mg/L with
13.8 MUmol H2 production after 12 h.
PMID- 28505531
TI - Rapid degradation, mineralization and detoxification of pharmaceutically active
compounds in aqueous solution during pulsed corona discharge treatment.
AB - In the present study, plasma generated by pulsed corona discharge was used for
the degradation of diclofenac, carbamazepine and ciprofloxacin. Pollutants in
aqueous solution were plasma treated under two categories: single and mixed
pollutant condition. Mixed pollutant condition showed an antagonistic behaviour
and thus the degradation time was higher for mixed condition compared to the
single condition. At different voltage and frequencies, degradation efficiency
followed the trend, diclofenac>carbamazepine>ciprofloxacin. Acidic pH slightly
favoured the degradation process whereas in presence of radical scavengers (HCO3
, CO32- and humic acid) the degradation yield was significantly decreased. With
an input power of 101.5 W, complete degradation was achieved within 4-16 min of
plasma treatment for pharmaceutical's concentrations of 1-10 mg/L. As the
pollutant concentration increased from 1 to 10 mg/L, the pseudo first order rate
constant decreased, while yield increased. Complete degradation pathway of
diclofenac, carbamazepine and ciprofloxacin in plasma treatment process are
proposed by identifying the intermediates using LC-MS analysis. TOC analysis
confirmed 80% mineralization within 10 min of plasma treatment for higher
pharmaceutical's concentrations of 10 mg/L. The microalgae ecotoxicity study and
disc diffusion test confirmed the complete detoxification of PACs that took place
after 6 min of plasma treatment.
PMID- 28505532
TI - Encapsulated Pseudomonas putida for phenol biodegradation: Use of a structural
membrane for construction of a well-organized confined particle.
AB - Phenols are toxic byproducts from a wide range of industry sectors. If not
treated, they form effluents that are very hazardous to the environment. This
study presents the use of a Pseudomonas putida F1 culture encapsulated within a
confined environment particle as an efficient technique for phenol
biodegradation. The innovative encapsulation technique method, named the "Small
Bioreactor Platform" (SBP) technology, enables the use of a microfiltration
membrane constructed as a physical barrier for creating a confined environment
for the encapsulated culture. The phenol biodegradation rate of the encapsulated
culture was compared to its suspended state in order to evaluate the
effectiveness of the encapsulation technique for phenol biodegradation. A maximal
phenol biodegradation rate (q) of 2.12/d was exhibited by encapsulated P. putida
at an initial phenol concentration of 100 mg/L. The biodegradation rate decreased
significantly at lower and higher initial phenol concentrations of 50 and up to
3000 mg/L, reaching a rate of 0.1018/d. The results also indicate similar and up
to double the degradation rate between the two bacterial states (encapsulated vs.
suspended). High resolution scanning electron microscopy images of the SBP
capsule's membrane morphology demonstrated a highly porous microfiltration
membrane. These results, together with the long-term activity of the SBP capsules
and verification that the culture remains pure after 60 days using 16S rRNA gene
phylogenetic affiliation tests, provide evidence for a successful application of
this new encapsulation technique for bioaugmentation of selected microbial
cultures in water treatment processes.
PMID- 28505533
TI - Discovery and characterization of selective human sphingomyelin synthase 2
inhibitors.
AB - Sphingomyelin synthase (SMS) is a membrane enzyme that catalyzes the synthesis of
sphingomyelin, is required for the maintenance of plasma membrane microdomain
fluidity, and has two isoforms: SMS1 and SMS2. Although these isoforms exhibit
the same SMS activity, they are different enzymes with distinguishable
subcellular localizations. It was reported that SMS2 KO mice displayed lower
inflammatory responses and anti-atherosclerotic effects, suggesting that
inhibition of SMS2 would be a potential therapeutic approach for controlling
inflammatory responses and atherosclerosis. This study aimed to discover a novel
small-molecule compound that selectively inhibits SMS2 enzymatic activity. We
developed a human SMS2 enzyme assay with a high-throughput mass spectrometry
based screening system. We characterized the enzymatic properties of SMS2 and
established a high-throughput screening-compatible assay condition. To identify
human SMS2 inhibitors, we conducted compound screening using the enzyme assay. We
identified a 2-quinolone derivative as a SMS2 selective inhibitor with an IC50 of
950 nM and >100-fold selectivity for SMS2 over SMS1. The 2-quinolone exhibited
efficacy in a cell-based engagement assay. We demonstrated that a more potent
derivative directly bound to SMS2-expressing membrane fractions in an affinity
selection mass spectrometry assay. Mutational analyses revealed that the
interaction of the inhibitor with SMS2 required the presence of the amino acids
S227 and H229, which are located in the catalytic domain of SMS2. In conclusion,
we discovered novel SMS2-selective inhibitors. 2-Quinolone SMS2 inhibitors are
considered applicable for leading optimization studies. Further investigations
using these SMS2 inhibitors would provide validation tools for SMS2-relevant
pathways in vitro and in vivo.
PMID- 28505534
TI - Discorhabdin alkaloids from Antarctic Latrunculia spp. sponges as a new class of
cholinesterase inhibitors.
AB - The brominated pyrroloiminoquinone alkaloids discorhabdins B, L and G and 3
dihydro-7,8- dehydrodiscorhabdin C, isolated from methanol extracts of two
specimens of Latrunculia sp. sponges collected near the Antarctic Peninsula, are
here demonstrated for the first time to be reversible competitive inhibitors of
cholinesterases. They showed Ki for electric eel acetylcholinesterase of 1.6-15.0
MUM, for recombinant human acetylcholinesterase of 22.8-98.0 MUM, and for horse
serum butyrylcholinesterase of 5.0-76.0 MUM. These values are promising when
compared to the current cholinesterase inhibitors used for treatment of patients
with Alzheimer's disease, to counteract the acetylcholine deficiency in the
brain. Good correlation was obtained between IC50 data and results by molecular
docking calculation on the binding interactions within the acetylcholinesterase
active site, which also indicated the moieties in discorhabdin structures
involved. To avoid unwanted peripheral side effects that can appear in patients
using some acetylcholinesterase inhibitors, electrophysiological experiments were
carried out on one of the most active of these compounds, discorhabdin G, which
confirmed that it had no detectable undesirable effects on neuromuscular
transmission and skeletal muscle function. These findings are promising for
development of cholinesterase inhibitors based on the scaffold of discorhabdins,
as potential new agents for treatment of patients with Alzheimer's disease.
PMID- 28505535
TI - Thiosemicarbazones and 4-thiazolidinones indole-based derivatives: Synthesis,
evaluation of antiproliferative activity, cell death mechanisms and topoisomerase
inhibition assay.
AB - In this study, we report the synthesis and structural characterization of a
series of thiosemicarbazone and 4-thiazolidinones derivatives, as well as their
in vitro antiproliferative activity against eight human tumor cell lines. For the
most potent compound further studies were performed evaluating cell death
induction, cell cycle profile, ctDNA interaction and topoisomerase IIalpha
inhibition. A synthetic three-step route was established for compounds (2a-e and
3a-d) with yields ranging from 32 to 95%. Regarding antiproliferative activity,
compounds 2a-e and 3a-d showed mean GI50 values ranging between 1.1 MUM (2b) -
84.65 MUM (3d). Compound 2b was the most promising especially against colorectal
adenocarcinoma (HT-29) and leukemia (K562) cells (GI50 = 0.01 MUM for both cell
lines). Mechanism studies demonstrated that 24 h-treatment with compound 2b (5
MUM) induced phosphatidylserine residues exposition and G2/M arrest on HT-29
cells. Moreover, 2b (50 MUM) was able to interact with ctDNA and inhibited
topoisomerase IIalpha activity. These results demonstrate the importance of
thiosemicarbazone, especially the derivative 2b, as a promising candidate for
anticancer therapy.
PMID- 28505536
TI - Design, synthesis, molecular docking and cytotoxic evaluation of novel 2
furybenzimidazoles as VEGFR-2 inhibitors.
AB - Inhibition of angiogenesis through inhibition of vascular endothelial growth
factor receptor 2 (VEGFR-2) has been applied in cancer therapy because of its
important role in promoting cancer growth and metastasis. In the presented study,
a series of benzimidazol-furan hybrids was designed and synthesized through
facile synthetic pathways. Evaluation of the synthesized compounds for their in
vitro cytotoxic activity against breast (MCF-7) and hepatocellular (HepG2)
carcinoma cell lines was performed. Two of the synthesized conjugates, 10b and
15, showed potent antiproliferative properties against MCF-7 cell line (IC50 =
21.25, 21.35 MUM, respectively) in comparison to tamoxifen (IC50 = 21.57 MUM).
Additionally, compounds 10a, 10b, 15 and 17 showed promising potency (IC50 =
25.95, 22.58, 26.94 and 31.06 MUM, respectively) against liver carcinoma cell
line HepG2 in contrast to cisplatin (IC50 = 31.16 MUM). Moreover, in vitro
evaluation of the synthesized compounds for their effect on the level of VEGFR-2
in MCF-7 cell line showed their potent inhibitory activity relative to control
untreated cells. Four compounds 10a, 10b, 14 and 15 showed 92-96% reduction in
VEGFR-2 level, compared with tamoxifen and sorafenib which showed inhibition
percentage of 98% and 95.75%, respectively. Compound 10a was found to have
promising VEGFR-2 inhibitory activity (IC50 = 0.64 MUM) in comparison to
sorafenib (IC50 = 0.1 MUM). Molecular docking was performed to study the binding
pattern of the newly synthesized compounds with VEGFR-2 active site. Molecular
docking attributed their good VEGFR-2 inhibitory activity to their hydrogen
bonding interaction with the key amino acids in VEGFR-2 active site, Glu885 and
Asp1046, and their hydrophobic interaction by their 2-furylbenzimidazole moiety
with the allosteric hydrophobic back pocket in a type III inhibitors-like binding
mode. The binding interaction is augmented by a ring substituent with long chain
extension at position 1 of the benzimidazole due to its hydrophobic interaction
with the hydrophobic side chains of the amino acids at the interface between the
ATP binding site and the allosteric back pocket. Structure-activity relationship
(SAR) was inferred for future optimization based on the performed biological and
docking studies.
PMID- 28505537
TI - Investigation of pyrazolo-sulfonamides as putative small molecule oxytocin
receptor agonists.
AB - The neuropeptide oxytocin has been implicated in multiple central nervous system
functions in mammalian species. Increased levels have been reported to improve
trust, alleviate symptoms related to autism and social phobias, and reduce social
anxiety. Hoffman-La Roche published a patent claiming to have found potent small
molecule oxytocin receptor agonists, smaller than the first non-peptide oxytocin
agonist reported, WAY 267,464. We selected two of the more potent compounds from
the patent and, in addition, created WAY 267,464 hybrid structures and determined
their oxytocin and vasopressin receptor activity. Human embryonic kidney and
Chinese hamster ovary cells were used for the expression of oxytocin or
vasopressin 1a receptors and activity assessed via IP1 accumulation assays and
calcium FLIPR assays. The results concluded that the reported compounds in the
patent and the hybrid structures have no activity at the oxytocin or vasopressin
1a receptors.
PMID- 28505538
TI - Synthesis and pharmacological evaluation of neurosteroid photoaffinity ligands.
AB - Neuroactive steroids are potent positive allosteric modulators of GABAA receptors
(GABAAR), but the locations of their GABAAR binding sites remain poorly defined.
To discover these sites, we synthesized two photoreactive analogs of alphaxalone,
an anesthetic neurosteroid targeting GABAAR, 11beta-(4-azido-2,3,5,6
tetrafluorobenzoyloxy)allopregnanolone, (F4N3Bzoxy-AP) and 11-aziallopregnanolone
(11-AziAP). Both photoprobes acted with equal or higher potency than alphaxalone
as general anesthetics and potentiators of GABAAR responses, left-shifting the
GABA concentration - response curve for human alpha1beta3gamma2 GABAARs expressed
in Xenopus oocytes, and enhancing [3H]muscimol binding to alpha1beta3gamma2
GABAARs expressed in HEK293 cells. With EC50 of 110 nM, 11-AziAP is one the most
potent general anesthetics reported. [3H]F4N3Bzoxy-AP and [3H]11-AziAP, at
anesthetic concentrations, photoincorporated into alpha- and beta-subunits of
purified alpha1beta3gamma2 GABAARs, but labeling at the subunit level was not
inhibited by alphaxalone (30 MUM). The enhancement of photolabeling by 3H
azietomidate and 3H-mTFD-MPAB in the presence of either of the two steroid
photoprobes indicates the neurosteroid binding site is different from, but
allosterically related to, the etomidate and barbiturate sites. Our observations
are consistent with two hypotheses. First, F4N3Bzoxy-AP and 11-aziAP bind to a
high affinity site in such a pose that the 11-photoactivatable moiety, that is
rigidly attached to the steroid backbone, points away from the protein. Second,
F4N3Bzoxy-AP, 11-aziAP and other steroid anesthetics, which are present at very
high concentration at the lipid-protein interface due to their high
lipophilicity, act via low affinity sites, as proposed by Akk et al.
(Psychoneuroendocrinology2009, 34S1, S59-S66).
PMID- 28505539
TI - Revisiting bilateral thalamotomy for tremor.
AB - MRI guided focused ultrasound surgery (MRgFUS) has been FDA approved for
unilateral treatment of essential tremor (ET). Before this non-incisional
lesioning method can be applied to the treatment of both hemispheres the previous
experience with bilateral thalamic ablation must be addressed. In particular, the
high incidence of worsening of speech and balance associated with bilateral
surgical thalamotomy, a rationale for the development of deep brain stimulation.
The highest incidence of these complication occurred in the early years of
surgery for movement disorders, when neither MRI nor current stereotactic methods
were available. The vast majority of these initial patients suffering these
complications had Parkinson's disease where approximately 30% developed worsening
dysarthria and ataxia after bilateral thalamotomy. Patients suffering these
complications commonly had baseline abnormalities in speech and balance or
worsening symptoms after a first unilateral procedure. The more contemporary
experience with bilateral thalamotomy in the ET population is both much more
limited in patient numbers (includes patients after Gamma Knife radiosurgery),
and shows a much lower rate of these complications (approximately 5%). This more
recent experience suggests that bilateral thalamotomy using closed incisionless
methods such as MRgFUS has the potential to safely improve ET patients with axial
or bilateral limb involvement, if done in a staged manner excluding patients with
baseline dysarthria or ataxia or transient worsening of these symptoms following
a unilateral procedure.
PMID- 28505540
TI - Salivary protective factors in patients suffering from decompensated type 2
diabetes.
AB - PURPOSE: Defining the level of protective factors in saliva of patients suffering
from decompensated type 2 diabetes. MATERIAL AND METHODS: 50 Patients with
diagnosis of decompensated type 2 diabetes, including 32 women and 18 men at the
age of 57.9+/-9.2 years. The control group consisted of 50 people among whom
there were 38 women and 12 men whose average age was estimated at 51.2+/-9.9
years. RESULTS: It was stated the increased concentration of total protein by 60%
and decreased concentration of IgA by 70%, of lysozyme by 27% and of lactoferrin
by 40% in resting saliva of patients with type 2 diabetes if compared to the
control group. These outcomes were really statistically meaningful. The
evaluation of dependences between the analyzed protective factors and the
indicator of oral cavity condition proved the positive correlation between the
concentration of total protein and the number of DMFT (i.e. the rate of caries
intensity). The remaining coefficients of correlation being evaluated proved to
be negative and statistically meaningless. CONCLUSION: The obtained outcomes
prove a high influence of proteins included in saliva on the prevalence and
development of caries at patients with decompensated type 2 diabetes.
PMID- 28505541
TI - Retirement blues.
AB - This paper analyses the short- and longer-term effects of retirement on mental
health in ten European countries. It exploits thresholds created by state pension
ages in an individual-fixed effects instrumental-variable set-up, borrowing
intuitions from the regression-discontinuity design literature, to deal with
endogeneity in retirement behaviour. The results display no short-term effects of
retirement on mental health, but a large negative longer-term impact. This impact
survives a battery of robustness tests, and applies to women and men as well as
people of different educational and occupational backgrounds similarly. Overall,
the findings suggest that reforms inducing people to postpone retirement are not
only important for making pension systems solvent, but with time could also pay a
mental health dividend among the elderly and reduce public health care costs.
PMID- 28505542
TI - Computational modeling of protein assemblies.
AB - Computational methods to predict the 3D structures of protein interactions fall
into 3 categories-template based modeling, protein-protein docking and
hybrid/integrative modeling. The two most important considerations for modeling
methods are sampling and scoring conformations. Sampling has benefitted from
techniques such as fast Fourier transforms (FFT), spherical harmonics and higher
order manifolds. Scoring complexes to determine binding free energy is still a
challenging problem. Rapid advances have been made in hybrid modeling where
experimental data are amalgamated with computations. These methods have received
a boost from the popularity of experimental methods such as electron microscopy
(EM). While increasingly larger and complicated complexes are now getting
elucidated by integrative methods, modeling conformational flexibility remains a
challenge. Ongoing improvements to these techniques portend a future where
organelles or even cells could be accurately modeled at a molecular level.
PMID- 28505543
TI - Chronic administration of apple polyphenols ameliorates hyperglycaemia in high
normal and borderline subjects: A randomised, placebo-controlled trial.
AB - AIMS: We previously reported that apple polyphenols (AP) and their major active
components, procyanidins, had beneficial effects on glucose homeostasis and
diabetes in diabetic ob/ob mice. The present study was performed to evaluate the
effects of chronic AP administration on glucose tolerance in high-normal and
borderline human subjects. METHODS: Subjects (n=65) with a fasting plasma glucose
(FPG) level of 100-125mg/dL determined during a recent health check-up were
randomised to receive tablets containing AP (600mg/day) or placebo tablets for
12weeks in a double-blinded, placebo-controlled clinical trial. The primary
outcome was insulin resistance, assessed using a 75g oral glucose tolerance test
(OGTT). RESULTS: The 12-week chronic administration of AP significantly reduced
the increase in glucose at 30-min post-75g OGTT (OGTT30-min glucose) value,
compared to the placebo regimen. Furthermore, in a subgroup of the high-normal
(FPG value, 100-109mg/dL; 2-h post-75g OGTT glucose (OGTT2-h glucose) value,
<140mg/dL) and borderline (FPG value, 110-125mg/dL; OGTT2-h glucose value,
<140mg/dL and FPG value, <126mg/dL; OGTT2-h glucose value, 140-199mg/dL)
subjects, OGTT30-min glucose value in the AP group (164.0+/-7.4mg/dL) was
significantly lower than that of the placebo group (194.7+/-10.4mg/dL, p<0.05).
No significant changes in the other lipid parameters and cytokine levels were
observed. CONCLUSIONS: Chronic AP administration significantly improved impaired
glucose tolerance in high-normal and borderline subjects. Larger and/or longer
term scale human studies are required to confirm the potential glucose
homeostasis of AP.
PMID- 28505544
TI - Real-life experience of patients starting insulin degludec. A multicenter
analysis of 1064 subjects from the German/Austrian DPV registry.
AB - BACKGROUND: The long-acting insulin analogue degludec is a therapeutic option for
patients with type 1 (T1D) or type 2 diabetes (T2D). Aim of this analysis was to
investigate differences in clinical characteristics of patients before and after
initiating degludec use in a cohort of German/Austrian patients. METHODS: 1064
subjects with T1D/T2D and documented degludec use from the Diabetes-Patient
Follow-Up (DPV) registry were included. The follow-up cohort (n=421) comprised
patients with available data before and 3-15months after switching to degludec. A
t-test for paired values was implemented to compare rates of severe
hypoglycaemia, and mean values for HbA1C, BMI, basal insulin dose/kg
bodyweight/day, and the number of basal insulin injections/day before and after
switching to degludec Results were stratified by type of diabetes. In T1D,
subgroup analyses were conducted (age, sex, basal insulin used before switching).
P<0.05 was considered significant. FINDINGS: In T1D (n=360), basal insulin dose
(0.43+/-0.17 to 0.38+/-0.13IU) and the number of basal injections/day (1.7+/-0.6
to 1.1+/-0.3) decreased whereas BMI increased from 23.2+/-4.8 to 24.0+/-5.0kg/m2
(all p<0.0001) after switching to degludec. No significant changes were observed
regarding rates of severe hypoglycaemia or HbA1C-values. Findings were comparable
for subgroups. In T2D (n=61), basal insulin dose (0.41+/-0.23 to 0.38+/-0.21;
p=0.1730) and the number of basal injections/day (1.3+/-0.4 to 1.1+/-0.3;
p=0.0097) decreased after switching to degludec. HbA1C improved from 7.9+/-1.6 to
7.1+/-1.5% (p<0.0001). CONCLUSIONS: The DPV registry provides data from real-life
diabetes care. Our analysis predominantly confirmed results from clinical trials
and provides additional information complementing the clinical study program of
degludec.
PMID- 28505545
TI - Leg stiffness during sprinting in transfemoral amputees with running-specific
prosthesis.
AB - Carbon fiber running-specific prostheses are designed to reproduce the spring
like stepping behavior of individuals similar to springs loaded by the entire
body mass (i.e. spring-mass model). The aim of this study was to test whether leg
stiffness would be modulated differently between intact and prosthetic legs in
transfemoral amputees wearing RSP during sprinting. Eight unilateral transfemoral
amputees performed maximum sprinting along an indoor overground runway. Leg
stiffness was calculated from kinetic and kinematic data in intact and prosthetic
legs. The results showed that leg stiffness was for the prosthetic limb
approximately 12% decreased compared to the intact limb. Although there was no
difference in leg compression between the legs, maximal vertical ground reaction
force was significantly greater in the intact leg than in the prosthetic one.
These results indicate that asymmetric modulation of leg stiffness in
transfemoral amputees with running-specific prostheses is mainly associated with
asymmetric ground reaction force.
PMID- 28505546
TI - Quantifying sources of variability in gait analysis.
AB - Measurements from gait analysis are affected by many sources of variability.
Schwartz et al. [1] illustrated an experimental design and methods to estimate
these variance components. However, the derivation contains errors which could
severely bias the estimation of some components. Therefore, in this paper, we
presented correction to this method using ANOVA and Likelihood methods.
Furthermore, we demonstrated how commonly used reliability indices like CMC and
ICC may be derived from the variance components. We advocate the use of the
variance components, in preference to reliability indices, because the variance
components are easier to interpret, with understandable units.
PMID- 28505547
TI - Synthesis of indole analogs as potent beta-glucuronidase inhibitors.
AB - Natural products are the main source of motivation to design and synthesize new
molecules for drug development. Designing new molecules against beta
glucuronidase inhibitory is utmost essential. In this study indole analogs (1-35)
were synthesized, characterized using various spectroscopic techniques including
1H NMR and EI-MS and evaluated for their beta-glucuronidase inhibitory activity.
Most compounds were identified as potent inhibitors for the enzyme with IC50
values ranging between 0.50 and 53.40MUM, with reference to standard d-saccharic
acid 1,4-lactone (IC50=48.4+/-1.25MUM). Structure-activity relationship had been
also established. The results obtained from docking studies for the most active
compound 10 showed that hydrogen bond donor features as well as hydrogen bonding
with (Oepsilon1) of nucleophilic residue Glu540 is believed to be the most
importance interaction in the inhibition activity. It was also observed that
hydroxyl at fourth position of benzylidene ring acts as a hydrogen bond donor and
interacts with hydroxyl (OH) on the side chain of catalysis residue Tyr508. The
enzyme-ligand complexed were being stabilized through electrostatic pi-anion
interaction with acid-base catalyst Glu451 (3.96A) and thus preventing Glu451
from functioning as proton donor residue.
PMID- 28505548
TI - Enzymatic synthesis and semi-preparative isolation of N-acetylmuramic acid 6
phosphate.
AB - N-acetylmuramic acid 6-phosphate (MurNAc-6P) is a constituent of the bacterial
peptidoglycan cell wall, serving as an anchor point of secondary cell wall
polymers such as teichoic acids, and it is a key metabolite of the peptidoglycan
recycling metabolism. Thus, there is a demand for MurNAc-6P as a standard for
cell wall compositional and metabolic analyses and, in addition, as a substrate
for peptidoglycan recycling enzymes, e.g. MurNAc-6P etherases (MurQ) and MurNAc
6P phosphatases (MupP), or as an effector molecule of transcriptional MurR
regulators. However, MurNAc-6P is commercially not available. We report here the
facile enzymatic production of MurNAc-6P in mg-scale from MurNAc and ATP,
applying Clostridium acetobutylicum kinase MurK, and purification by semi
preparative HPLC. MurNAc-6P was quantified using a coupled enzyme assay,
revealing 75-80% overall product yield, and high purity was confirmed by mass
spectrometry and proton NMR.
PMID- 28505549
TI - Intramammary inoculation of Panax ginseng plays an immunoprotective role in
Staphylococcus aureus infection in a murine model.
AB - The immunoprotective effect of Panax ginseng (Pg) extract was investigated in a
mouse mastitis model. Lactating female mice were intramammarily inoculated with
Pg or placebo, and then were challenged with S. aureus, while other group was
inoculated with S. aureus alone. The number of bacteria recovered from mammary
glands was significantly lower in Pg-treated S. aureus-infected mice (group I)
compared with placebo-treated S. aureus-infected mice (group II) and S. aureus
infected mice (group III). The mRNA expression of TLR2, TLR4, IL-1alpha and TNF
alpha was influenced by treatment; being the transcript levels for all genes
higher in group I compared with group II and III. Activation of NF-kappaB and the
number of monocytes-macrophages in mammary gland tissue was significantly
increased in group I compared with group II and III. Pg extract was able to
trigger an adequate immune response to confront an infection demonstrating its
protective effect and potential for preventing bovine intramammary infections.
PMID- 28505550
TI - Histological differences in the adrenal glands and cortisol levels of suckling
dairy goat kids in enriched and non-enriched environments.
AB - Intensive production systems can negatively affect the welfare of goats.
Environmental enrichment techniques can be used to reduce stress. The aim of this
study was analyze the effect of environmental enrichment on the histological
characteristics of adrenal glands, cortisol levels and weekly weight gain of
suckling Alpine French male kids under confinement. A randomised design was used
to test the effect of the treatment. The animals (n=20) were randomly assigned to
two treatments (enriched and non-enriched) with two replicates each. Enrichment
elements included elevated sacks of henequen, trunks, tires and coconuts. The
cortisol levels were measured weekly. Male kids were euthanized when their weight
reached 10kg, and immediately after euthanasia, samples of the adrenal glands
were collected. The adrenal glands were weighed and measured, and histological
sections were taken and fixed. Four hundred cells were measured from each animal,
with two blind measurements taken from each sample. There were no significant
differences between experimental groups (P>0.05) in the weigh, size, the area of
cells from the glomerulosa and fasciculata areas of the adrenal glands, the
cortisol levels and weekly weight gain. However, there were histological
differences between the glomerular and fascicular zones of the left and right
adrenal glands of the different groups (P<0.05). These findings suggest that
adrenal glands of animals in non-enriched environment, contained histological
changes, suggestive of increased activity. We suggest testing adrenal histology
as an indicator of stress and recommend the use of environmental enrichment as a
means to reduce stress.
PMID- 28505551
TI - The "80 Joule criterion" reconsidered today.
AB - The 80 Joule or 58 ft-lb injury criterion first mentioned by Rohne was read in
his textbook and analyzed in detail. Additional review of early literature to
this topic was performed. Neither Rohne nor ballisticians ten years later gave an
indication how the 8mkg value validates immobilization and how immobilization was
defined. The penetration performance of the bullet M/88 was successfully
demonstrated in the 80 Joule status when fired in the 100m/s domain from the
Gewehr 88. The bullets were fired into ballistic soap under laboratory firing
conditions of today. The evaluation of measured velocities, depth of penetration
and the recording with high speed camera and CT scan was performed. An acceptable
correlation was found between the kinetic energy deposited and the penetration
depth. The soap penetration in the 80 Joule status is surprisingly high and
substantiates Rohne's allegation of a human's immobilization from the
battlefield. A validation of the criterion was not possible and it is recommended
not to use an energy limit value to define any sort of incapacitation.
PMID- 28505552
TI - Probabilistic pharmacokinetic models of decompression sickness in humans, part 1:
Coupled perfusion-limited compartments.
AB - Decompression sickness (DCS) is a disease caused by gas bubbles forming in body
tissues following a reduction in ambient pressure, such as occurs in scuba
diving. Probabilistic models for quantifying the risk of DCS are typically
composed of a collection of independent, perfusion-limited theoretical tissue
compartments which describe gas content or bubble volume within these
compartments. It has been previously shown that 'pharmacokinetic' gas content
models, with compartments coupled in series, show promise as predictors of the
incidence of DCS. The mechanism of coupling can be through perfusion or
diffusion. This work examines the application of five novel pharmacokinetic
structures with compartments coupled by perfusion to the prediction of the
probability and time of onset of DCS in humans. We optimize these models against
a training set of human dive trial data consisting of 4335 exposures with 223 DCS
cases. Further, we examine the extrapolation quality of the models on an
additional set of human dive trial data consisting of 3140 exposures with 147 DCS
cases. We find that pharmacokinetic models describe the incidence of DCS for
single air bounce dives better than a single-compartment, perfusion-limited
model. We further find the U.S. Navy LEM-NMRI98 is a better predictor of DCS risk
for the entire training set than any of our pharmacokinetic models. However, one
of the pharmacokinetic models we consider, the CS2T3 model, is a better predictor
of DCS risk for single air bounce dives and oxygen decompression dives.
Additionally, we find that LEM-NMRI98 outperforms CS2T3 on the extrapolation
data.
PMID- 28505553
TI - Linking eating and weight control attitudes to relationship experiences: A large
scale survey of adolescent females.
AB - OBJECTIVE: To examine the extent to which family conflict, peer bullying and
psychological distress account for eating and weight loss attitudes in adolescent
females. This study examined the degree to which psychological distress mediated
the association between family conflict and eating and weight loss attitudes, and
the association of bullying and eating and weight loss attitudes. METHOD: Females
aged between 11 and 17 years (N = 5125) were recruited from schools in the State
of Victoria (Australia). Key measures included psychological distress, family
conflict, and bullying victimisation. RESULTS: A structural model showed good
fit, and all predictors were significant. Psychological distress mediated the
association between eating and weight loss attitudes, and family problems and
bullying. CONCLUSION: Family conflict and peer bullying were associated with
eating and weight loss attitudes and this association may occur via psychological
distress. Early intervention programs may benefit from a focus on family and peer
relationships.
PMID- 28505555
TI - Postcard Pick-me-up: The power of simple acts of kindness.
PMID- 28505554
TI - A mixed-method evaluation of a New Zealand based midwifery education development
unit.
AB - The Midwifery Development Education Service was established in the Birthing Unit
at Middlemore Hospital in South Auckland New Zealand in 2007. The service is
unique in the New Zealand midwifery context for the way it operates as a
collaboration between the education and health provider to optimise the clinical
learning experience of student midwives. This paper reports on the evaluation of
the Midwifery Development Education Service that was undertaken in 2015. The
evaluation captured the views and experience of students and midwives who had
been involved with, or had worked alongside, the service. A mixed-method approach
was adopted for the evaluation study, comprising of an anonymous on-line survey,
qualitative interviews and focus group discussion. Considerable satisfaction with
the service was identified. This article draws attention to participants'
perceptions of the service as supporting student midwives; the significance of
quality time in the provision of the clinical midwifery education; the situating
of the service at a unique vantage point (overseeing the needs of the university
and the hospital) and its impact upon the learning culture of education within
the unit. A potential tension is also identified between the provision of a
supportive learning environment and the assessment of student performance.
PMID- 28505556
TI - Building midwifery educator capacity using international partnerships: Findings
from a qualitative study.
AB - Midwifery educators play a critical role in strengthening the midwifery workforce
globally, including in low and lower-middle income countries (LMIC) to ensure
that midwives are adequately prepared to deliver quality midwifery care. The most
effective approach to building midwifery educator capacity is not always clear.
The aim of this study was to determine how one capacity building approach in
Papua New Guinea (PNG) used international partnerships to improve teaching and
learning. A qualitative exploratory case study design was used to explore the
perspectives of 26 midwifery educators working in midwifery education
institutions in PNG. Seven themes were identified which provide insights into the
factors that enable and constrain midwifery educator capacity building. The study
provides insights into strategies which may aid institutions and individuals
better plan and implement international midwifery partnerships to strengthen
context-specific knowledge and skills in teaching. Further research is necessary
to assess how these findings can be transferred to other contexts.
PMID- 28505557
TI - Follow-up of patients with localized breast cancer and first indicators of
advanced breast cancer recurrence: A retrospective study.
AB - We conducted a retrospective study to assess the follow-up of patients with
localized breast cancer and the first indicators of advanced breast cancer
recurrence. All patients with advanced breast cancer recurrence treated between
January 2010 and June 2016 in our institution were registered. Among these
patients, 303 patients initially treated for early breast cancer with curative
intent were identified. After initial curative treatment, follow-up involved the
oncologist, the general practitioner and the gynecologist in 68.0%, 48.9% and
19.1% of cases, respectively. The median DFI was 4 years for luminal A, 3.8 years
for luminal B, 3.7 years for HER2-positive and 1.5 years for TNBC (p = 0.07).
Breast cancer tumor marker was prescribed for 164 patients (54.1%). No difference
in terms of follow-up was observed according to the molecular subtype. Symptoms
were the primary indicator of relapse for 143 patients (47.2%). Breast cancer
recurrence was discovered by CA 15.3 elevation in 57 patients (18.8%) and by CAE
elevation in 3 patients (1%). The rate of relapse diagnosed by elevation of CA
15.3 or CAE was not statistically associated with the molecular subtype (p =
0.65). Luminal A cases showed a significantly higher rate of bone metastases (p =
0.0003). TNBC cases showed a significantly higher rate of local recurrence (p =
0.002) and a borderline statistical significant higher rate of lung/pleural
metastases (p = 0.07). Follow-up recommendations could be adapted in clinical
practice according to the molecular subtype. General practitioners should be more
involved by the specialists in breast cancer follow-up.
PMID- 28505558
TI - Oncoplastic techniques: Attitudes and changing practice amongst breast and
plastic surgeons in Great Britain.
AB - PURPOSE: The availability, acceptability and practice of oncoplastic surgery has
increased over the last 5 years. This study aims to describe how the breast and
plastic surgical workforce has adapted to provide oncoplastic breast surgery.
METHODS: A questionnaire was distributed to members of the Association of Breast
Surgery and BAPRAS, and results compared to a survey completed in 2010. RESULTS:
In 2010, 228 respondents completed the survey compared to 237 in 2015, of whom
204 were consultants (105 General or Breast Surgeons and 99 Plastic Surgeons).
The range of procedures performed by Plastic Surgeons has remained static, the
General and Breast Surgeons are performing proportionally more therapeutic
mammaplasty (p < 0.001), breast reduction/mastopexy, and latissimus dorsi
reconstructions. In 2015, surgeons are less concerned about the risks of
lipomodelling than in 2010, with an increase the proportion of breast (55% vs.
26%) and plastic (91% vs. 58%) surgeons performing the technique. DISCUSSION:
Specific concerns about oncoplastic surgery have decreased over the last five
years, with a greater proportion of surgeons performing oncoplastic surgery
including lipomodelling. The majority of breast surgeons in 2015 remain
interested in further training in oncoplastic techniques (75%) but over the last
5 years, plastic surgeons interest in further training in oncoplastic surgery has
dropped from 62% to 27%. About half of all breast and plastic surgeons felt that
oncoplastic surgery should be available for all women and oncological and wound
healing concerns had significantly reduced between 2010 and 2015 (p < 0.05).
PMID- 28505559
TI - A two phased study on health care professionals' perceptions of single or multi
use of intermittent catheters.
AB - AIMS: This two phase study aimed to explore health care professionals' teaching
and prescribing practice related to intermittent catheterisation and to identify
their perceptions about the possible implementation of a mixed (single and multi
use) package for intermittent catheterization. INTRODUCTION: Single-use
intermittent catheters are the norm in the UK although multi-use is common in
some other countries. A recent Cochrane review found no difference in
complications, including urinary tract infection rates, between those using
single or multi-use catheters. A flexible option of both multi-use and single use
intermittent catheters could provide users with more flexible choices in self
care. However, understanding health care professionals' perspectives is one of
the keys to developing a multi-use intervention. DESIGN: A qualitative research
framework using in-depth interviews to inform an on line survey. METHOD: In-depth
interviews were conducted with health care professionals based in the UK who
prescribe catheters, teach intermittent catheterisation or manage an intermittent
catheterisation service. The interviewees were selected to represent a range of
clinical areas, experience and professions - continence advisors, urology,
multiple sclerosis (MS) and spinal cord injury specialist nurses, and General
Practitioners. Following framework analysis the themes and factors identified
were used to develop an on-line survey which was disseminated through health care
professional networks whose members saw patients who use intermittent catheters.
RESULTS: Nineteen health care professionals participated in the telephone
interviews; 206 completed the survey. A wide range of professionals in terms of
experience and specialty afforded rich information regarding the contextual
issues around the teaching and prescribing of intermittent catheters. The primary
finding was that health care professionals were concerned about 'minimising
health risk' and maximising 'normalcy' for those using intermittent self
catheterisation. Health care professionals who worked in the acute setting or had
no experience of re-use were most resistant to the re-use of catheters.
Professionals requested evidence that a multi-use package would not increase the
risk of developing a urinary tract infection or increase the burden of use to a
patient before a mixed package would be considered. CONCLUSIONS: For multi-use to
be acceptable, evidence based guidelines must be available for healthcare
professionals and cleaning methods must be acceptable and safe for intermittent
catheter users. Further evidence may be required to establish that a mixed
catheter package is equivalent to single use only, particularly for outcomes such
as urinary tract infection, urethral injury and quality of life. RELEVANCE TO
CLINICAL PRACTICE: This paper highlights that if multi-use catheters are to be
successfully introduced into clinical practice, the ease of use, safety and
effectiveness of the cleaning technique will need to be convincingly demonstrated
by a range of well-defined users.
PMID- 28505560
TI - Integrated signal probe based aptasensor for dual-analyte detection.
AB - For the multi-analyte detection, although the sensitivity has commonly met the
practical requirements, the reliability, reproducibility and stability need to be
further improved. In this work, two different aptamer probes labeled with redox
tags were used as signal probe1 (sP1) and signal probe2 (sP2), which were
integrated into one unity DNA architecture to develop the integrated signal probe
(ISP). Comparing with the conventional independent signal probes for the
simultaneous multi-analyte detection, the proposed ISP was more reproducible and
accurate. This can be due to that ISP in one DNA structure can ensure the
completely same modification condition and an equal stoichiometric ratio between
sP1 and sP2, and furthermore the cross interference between sP1 and sP2 can be
successfully prevented by regulating the complementary position of sP1 and sP2.
The ISP-based assay system would be a great progress for the dual-analyte
detection. Combining with gold nanoparticles (AuNPs) signal amplification, the
ISP/AuNPs-based aptasensor for the sensitive dual-analyte detection was explored.
Based on DNA structural switching induced by targets binding to aptamer, the
simultaneous dual-analyte detection was simply achieved by monitoring the
electrochemical responses of methylene blue (MB) and ferrocene (Fc) This proposed
detection system possesses such advantages as simplicity in design, easy
operation, good reproducibility and accuracy, high sensitivity and selectivity,
which indicates the excellent application of this aptasensor in the field of
clinical diagnosis or other molecular sensors.
PMID- 28505561
TI - Class enzyme-based motors for "on the fly" enantiomer analysis of amino acids.
AB - Here, two class-enzyme motors are properly designed allowing the rapid dispersion
of the class-enzyme D-amino acid oxidase (DAO) and L-amino acid oxidase (LAO) for
selective "on the fly" biodetection of D and L-amino acids (AAs), respectively.
The efficient movement together with the continuous release of fresh class-enzyme
leads to a greatly accelerated enzymatic reaction processes without the need of
external stirring or chemical and physical attachment of the enzyme. Ultra-fast
detection (<2min) and accurate quantifications of L-phenylalanine (L-Phe) in
plasma and whole-blood newborns samples diagnosed with Phenylketonuria and total
D-AAs in Vibrio cholera cultures are pioneer illustrated as relevant examples of
each enantiomer determination. These results opens clearly novel avenues in
biosensing for fast screening diagnostics, decentralized monitoring and design of
future points of care.
PMID- 28505562
TI - Ultra-fast electronic detection of antimicrobial resistance genes using
isothermal amplification and Thin Film Transistor sensors.
AB - A low cost thin-film transistor (TFT) nanoribbon (NR) sensor has been developed
for rapid real-time detection of DNA amplification using an isothermal
Recombinase Polymerase Amplification (RPA) method. The semiconductor chip
measures DNA amplification through a pH change, rather than via fluorescence. The
utility of the method was demonstrated by amplifying CTX-M and NDM, two genes
that confer bacterial resistance to cephalosporins and carbapenems, respectively.
It is shown that this approach provides extremely fast and sensitive detection.
It can detect <10 copies of the gene in genomic DNA extracted from E. coli or K.
pneumoniae clinical isolates within a few minutes. A differential readout system
was developed to minimize the effect of primer-dimer amplification on the assay.
The simple device has the potential for low cost, portable and real-time nucleic
acid analysis as a Point of Care device.
PMID- 28505564
TI - Niches after cesarean section in a population seeking hysteroscopic
sterilization.
AB - OBJECTIVE: To study the prevalence of hysteroscopically evaluated disruptions of
the integrity of the uterine wall ('niches') in women with and without a previous
cesarean section. STUDY DESIGN: A prospective cohort study was performed in a
teaching hospital in the Netherlands. Women seeking hysteroscopic sterilization
were included. A hysteroscopic evaluation of the anterior wall of the uterus and
cervix to identify the existence of disruptions (niches) was performed in a
standard manner. Primary outcome was the presence of a uterine niche, defined as
any visible defect, disruption, or concavity (gap) in the anterior wall.
Secondary outcome was to develop a registration form of niche features for
hysteroscopic evaluation. RESULTS: In total, 713 women were included, 603 without
and 110 with a previous cesarean section. In women with a previous cesarean
Section 83 (75%) niches were observed using hysteroscopy. Anterior wall
disruptions were not observed in women without a cesarean section. The following
niche features were identified and incorporated in a registration form: polyps,
cysts, myometrium defect, fibrotic tissue, (abnormal) vascular pattern, lateral
branches, mucus production inside the defect, and bleeding. CONCLUSION: In a
prospective cohort study among women undergoing hysteroscopic sterilization, a
uterine niche could be detected by hysteroscopy in 75% of women with a previous
cesarean section.
PMID- 28505563
TI - Ultrasensitive magnetic field-assisted surface plasmon resonance immunoassay for
human cardiac troponin I.
AB - An ultrasensitive surface plasmon resonance (SPR) immunoassay was developed for
the specific detection of human cardiac troponin I (cTnI), a principle diagnostic
marker for myocardial damage. The thin gold film evaporated on a glass slate,
which was employed as the SPR sensing film, was modified by hollow gold
nanoparticles (HGNPs) and polydopamine (PDA) sequentially, and then was
immobilized with antibodies for specific recognition of target analyte.
Electronic coupling of the surface plasmon waves originating from the HGNPs and
the gold film leads to the remarkable amplification of SPR response. The PDA film
modified on the gold film via self-polymerization of dopamine (DA) facilitates
the direct immobilization of capture antibodies (cAb). To separate and enrich the
target analyte, PDA-wrapped magnetic multi-walled carbon nanotubes (MMWCNTs-PDA)
were conjugated with detection antibodies (dAb) and used as the extracting agent
for the magnetic extraction of cTnI in sample. Large surface area of MMWCNTs-PDA
ensures its loading capacity for dAb, as well as its extraction efficiency for
cTnI. By serving as the "vehicles" for fast delivering the concentrated analyte
to the SPR sensing surface, MMWCNTs-PDA-dAb also overcomes the disadvantage of
slow diffusion-limited mass transfer and matrix interference effect in regular
patterns. The combination of the above improvements results in the significant
sensitivity enhancement of the SPR immunoassay. The concentration of cTnI with
minimum detectable SPR response obtained by the present assay is 1.25ngmL-1,
which is 1000-fold lower than that obtained by the traditional SPR immunoassay
based on PDA-modified gold film.
PMID- 28505565
TI - DFT and TD-DFT theoretical studies on photo-induced electron transfer process on
[Cefamandole].C60 nano-complex.
AB - The C60 fullerene displays a considerable electronegativity. It has a unique
photophysical and electrochemical behavior that can be used as a suitable drug
carrier. In the present study, the interaction of C60 fullerene as an electron
recipient with the Cefamandole antibiotic was investigated in both ground and
excited states using DFT and TD-DFT methods. The study of the interaction of C60
and Cefamandole via electron localization function (ELF) and reduced density
gradient (RDG) revealed that the complex formation is of van der Waals type. The
data from natural bonding orbitals (NBO) analysis also confirmed the interaction
type. The study of absorption and emission spectrum via CAM-B3LYP in the TD-SCF
state showed that the emission peak of C60 fullerene in the 591.73nm after the
complex formation results in the extinction of this emission spectrum due to
charge transfer (CT) from chelator to fluorophore. The photoinduced electron
transfer (PET) process was investigated using the electron hole theory.
PMID- 28505567
TI - One-step versus two-step mechanism of Diels-Alder reaction of 1-chloro-1
nitroethene with cyclopentadiene and furan.
AB - DFT computational study shows that Diels-Alder (DA) reactions of 1-chloro-1
nitroethene with cyclopentadiene and furan have polar nature. However, their
mechanism is substantially different. In particular, 1-chloro-1-nitroethene react
with cyclopentadiene according to one-step mechanism. In the same time, more
favourable channel associated with the P-DA reaction between furan and 1-chloro-1
nitroethene is a domino process, that comprises an initial hetero-Diels-Alder
reaction yielding a [2+4] cycloadduct, which experiences a subsequent [3,3]
sigmatropic shift to yield the expected formal [4+2] cycloadduct. This is a
consequence of more polar nature of reaction, due to higher nucleophilicity of
furan in comparison to cyclopentadiene.
PMID- 28505566
TI - Conformational Study of the Structure of dibenzo-18-crown-6. Comparison with 18
crown-6.
AB - We report for the first time the conformational analysis of dibenzo-18-crown-6,
db18c6. The conformational search was carried out using the CONFLEX
conformational search method of cyclic molecules. Energies were calculated for
the low-lying predicted conformations at different levels of theory up to the
G3MP2 level. At the G3MP2 level, the predicted ground state (GS) conformation was
more stable than the experimental conformation by only 1.60kcal/mol. Strong
similarity was found between the GS structure and experimental conformations of
db18c6 and 18-crown-6, 18c6. The GS and experimental conformations of db18c6 are
non-planar. This allows db18c6 to exist in optically active enantiomers. Similar
to 18c6, it was concluded that the db18c6 structure is stabilized by
intramolecular hydrogen bond. We also performed the computations for the water
and chloroform solution phase, where the same conformation was predicted as the
GS conformation.
PMID- 28505568
TI - The structural relationship between early nutrition, cognitive skills and non
cognitive skills in four developing countries.
AB - This study provides evidence about how cognitive and non-cognitive skills are
acquired during childhood in four developing countries (Ethiopia, India, Peru and
Vietnam), highlighting the role of early nutrition as a determinant in this
process. An increase of one standard deviation in height-for-age at the age of 1
is found to have a total effect on cognitive skills at age 8 by 5.4 percent in
Ethiopia, 9.0 percent in India, 7.6 percent in Peru and 8.4 percent in Vietnam.
The corresponding total effect on non-cognitive skills is 1.1 percent in
Ethiopia, 3.4 percent in India, 2.6 percent in Peru and 1.7 percent in Vietnam.
The evidence suggests the effect of early nutrition on non-cognitive skills is
indirect, mediated by cognitive skills. The effect is also relatively small in
magnitude.
PMID- 28505569
TI - Comparison of the Hologic Aptima HIV-1 Quant Dx Assay to the Roche COBAS
Ampliprep/COBAS TaqMan HIV-1 Test v2.0 for the quantification of HIV-1 RNA in
plasma samples.
AB - BACKGROUND: HIV-RNA is the most important parameter for monitoring antiviral
treatment in individuals infected with HIV-1. Knowledge of the performance of
different tests for the quantification of HIV-1 RNA is therefore important for
clinical care. OBJECTIVES: To compare the analytical performance of the Aptima
HIV-1 Quant Dx Assay (Aptima) and the COBAS Ampliprep/COBAS TaqMan HIV-1 Test
v2.0 (CAPCTMv2) for the quantification of HIV-1 RNA in plasma samples. STUDY
DESIGN: The performance of the two tests was compared on 216 clinical plasma
samples, on dilutions series in seven replicates of five clinical samples of
known subtype and on ten replicates of the Acrometrix High and Low Positive
Control. RESULTS: Bland-Altman analysis of 130 samples that quantified in both
tests did not show indications of gross mis-quantification of either test. A
tendency of the Aptima assay to quantify higher at high viral load compared to
the CAPCTMv2 was observed in Bland-Altman analysis, by Deming regression (Slope
1.13) and in dilution series of clinical samples. Precision evaluated using the
Acrometrix Positive Controls was similar for the High Control (CV: 1.2% vs. 1.3%;
Aptima assay vs. CAPCTMv2 test, respectively), but differed for the Low control
(CV: 17.9% vs. 7.1%; Aptima assay vs. CAPCTMv2 test, respectively). However, this
did not impact clinical categorization of clinical samples at neither the 50
cp/mL nor 200 cp/mL level. CONCLUSION: The Aptima assay and the CAPCTMv2 test are
highly correlated and are useful for monitoring HIV-infected individuals.
PMID- 28505570
TI - Clinical evaluation of the BioFire FilmArray(r) BioThreat-E test for the
diagnosis of Ebola Virus Disease in Guinea.
AB - BACKGROUND: The recent West Africa Ebola outbreak highlighted the need to provide
access to rapid, safe and reliable Ebola Virus Disease diagnostics. OBJECTIVES:
The objective of this field study was to assess the clinical performance of the
FilmArray(r) BioThreat-E test for the detection of Ebola Zaire virus in whole
blood in symptomatic patients suspected of Ebola Virus Disease in Conakry
(Guinea) from March to July 2015. STUDY DESIGN: The BioThreat-E test was compared
to the two RT-PCRs, using serum, implemented at Donka Hospital in the emergency
context: an in-house developed quantitative one-step RT-PCR adapted from the
Weidmann technique, and the RealStar(r) Filovirus RT-PCR Kit 1.0 (Altona
Diagnostics). We also assessed the performance of this assay in noninvasive
specimens (urine and saliva) to detect infected patients. RESULTS: Of 135
patients enrolled and eligible for performance assessment on whole blood, the
sensitivity was 95.7% [95% CI: 85.5-99.5] and specificity 100% [95% CI: 95.9
100]. Of the 37 symptomatic infected patients able to provide saliva and/or urine
samples, 34 of the 35 saliva samples and all 3 of the urine samples were positive
with the BioThreat-E test. CONCLUSIONS: This study showed that the FilmArray
BioThreat-E test performs comparably to conventional molecular tests under field
conditions, providing results and interpretation in approximately 1h. Due to its
operational characteristics, it can be easily deployed in the field during an
epidemic and could also be a useful tool for post-outbreak surveillance.
PMID- 28505572
TI - Challenges in using allylthiourea and chlorate as specific nitrification
inhibitors.
AB - Allylthiourea (ATU) and chlorate (ClO3-) are often used to selectively inhibit
nitritation and nitratation. In this work we identified challenges with use of
these compounds in inhibitory assays with filter material from a biological rapid
sand filter for groundwater treatment. Inhibition was investigated in continuous
flow lab-scale columns, packed with filter material from a full-scale filter and
supplied with NH4+ or NO2-. ATU concentrations of 0.1-0.5 mM interfered with the
indophenol blue method for NH4+ quantification leading to underestimation of the
measured NH4+ concentration. Interference was stronger at higher ATU levels and
resulted in no NH4+ detection at 0.5 mM ATU. ClO3- at typical concentrations for
inhibition assays (1-10 mM) inhibited nitratation by less than 6%, while
nitritation was instead inhibited by 91% when NH4+ was supplied. On the other
hand, nitratation was inhibited by 67-71% at 10-20 mM ClO3- when NO2- was
supplied, suggesting significant nitratation inhibition at higher NO2-
concentrations. No chlorite (ClO2-) was detected in the effluent, and thus we
could not confirm that nitritation inhibition was caused by ClO3- reduction to
ClO2-. In conclusion, ATU and ClO3- should be used with caution in inhibition
assays, because analytical interference and poor selectivity for the targeted
process may affect the experimental outcome and compromise result interpretation.
PMID- 28505571
TI - Re-evaluation of routine dengue virus serology in travelers in the era of Zika
virus emergence.
AB - BACKGROUND: Diagnostic requests for both Zika virus (ZIKV) and dengue virus
(DENV) infections in returning travelers have significantly increased during the
recent ZIKV outbreak in the Americas. These flaviviruses have overlapping
clinical syndromes and geographical distribution, but diagnostic differentiation
is important because of different clinical consequences. As flaviviruses are
known to have a short viremic period, diagnostics often rely on serological
methods, which are challenging due to extensive cross-reactive antibodies.
OBJECTIVE: To re-evaluate the performance of DENV serological assays in
laboratory confirmed ZIKV-infected travelers. STUDY DESIGN: The extent of cross
reactivity of the DENV NS1 antigen, IgM and IgG ELISA was analyzed in 152
clinical blood samples collected from 69 qRT-PCR and 24 virus neutralization
titer (VNT) confirmed ZIKV-infected travelers. RESULTS: The majority of travelers
in the presented cohort returned to the Netherlands from Suriname and presented
with symptoms of fever and rash. Twenty-three percent of the female travelers
were pregnant. None of the 39 ZIKV RNA positive blood samples were cross-reactive
in the DENV NS1 antigen ELISA. The rates of cross-reactivity of the DENV IgM and
IgG ELISAs were 31% and 54%, respectively, after excluding travelers with
(potential) previous DENV exposure. CONCLUSIONS: Although the DENV NS1 antigen
assay was highly specific in this cohort of laboratory confirmed ZIKV-infected
travelers, we demonstrate high percentages of cross-reactivity of DENV IgM and
IgG ELISAs of which diagnostic laboratories should be aware. In addition, the
high rate of DENV IgG background of >25% complicates a proper serological
diagnosis in this group.
PMID- 28505573
TI - Effect of inorganic regenerant properties on pharmaceutical adsorption and
desorption performance on polymer anion exchange resin.
AB - This study investigated the potential effect of four frequently used inorganic
regenerant properties (i.e., ionic strength, cation type, anion type, and
regeneration solution volume) on the desorption and adsorption performance of 14
pharmaceuticals, belonging to 12 therapeutic classes with different predominant
chemical forms and hydrophobicities, using polymeric anion exchange resin (AER)
packed fixed-bed column tests. After preconditioning with NaCl, NaOH, or saline
alkaline (SA) solutions, all resulting mobile counterion types of AERs
effectively adsorbed all 14 pharmaceuticals, where the preferential magnitude of
OH--type = Cl- + OH--type > Cl--type. During regeneration, ionic strength (1 M
versus 3 M NaCl) had no significant influence on desorption performance for any
of the 14 pharmaceuticals, while no regenerant cation (HCl versus NaCl) or anion
type (NaCl versus NaOH and SA) achieved higher desorption efficiencies for all
pharmaceuticals. A volumetric increase in 1 M or 3 M NaCl solutions significantly
improved the desorption efficiencies of most pharmaceuticals, irrespective of
ionic strength. The results indicate that regeneration protocols, including
regenerant cation type, anion type and volume, should be optimized to improve
pharmaceutical removal by AERs.
PMID- 28505574
TI - The effect of insecticides chlorpyrifos, alpha-cypermethrin and imidacloprid on
primary DNA damage, TP 53 and c-Myc structural integrity by comet-FISH assay.
AB - In parallel with the continuous use of conventional insecticides, introduction of
more environmentally friendly substances continues to grow in modern agriculture.
In the present study, we evaluated chlorpyrifos, and imidacloprid and alpha
cypermethrin as two representatives of green insecticides for their genotoxic
activity. We conducted a 14-day treatment in extended human lymphocytes cultures
using real life exposure relevant concentrations. An alkaline comet assay was
used to detect primary DNA damage. Simultaneously, the effect on the specific
action towards the TP 53 and c-Myc genes in terms of fragmentation and copy
number were determined. Both genes are responsible for cell cycle regulation;
thus playing an active role in carcinogenesis. Contrary to what was expected,
imidacloprid showed the highest genotoxicity potential, irrespective of the fact
that none of the insecticides induced a significant level of primary DNA damage
at all tested concentrations. Similar, no significant effect towards the TP 53
and c-Myc gene was recorded. The present study indicates that low level use of
chlorpyrifos as a conventional insecticide and imidacloprid and alpha
cypermethrin as green insecticides does not pose a risk to DNA in general, nor to
the TP 53 and c-Myc gene structural integrity.
PMID- 28505575
TI - Synthesis, characterization and photocatalytic properties of nanostructured
CoFe2O4 recycled from spent Li-ion batteries.
AB - In this study, cobalt (Co) was recycled from spent lithium ion batteries (LIBs)
and used to synthesize cobalt ferrite (CoFe2O4-LIBs), which was applied as a
catalyst for heterogeneous photo Fenton reactions that discolored methylene blue
(MB) dye. The co-precipitation method was used to synthesize CoFe2O4-LIBs and
CoFe2O4-R nanoparticles with spinel structures using as raw materials of the LIB
cathodes and commercial reagents. X-ray diffraction (XRD) identified the
formation of spinel-type CoFe2O4, which formed clusters that could be seen under
scanning electron microscopy (SEM) analysis and nanometric particles seen under
transmission electron microscopy (TEM). Inductively Coupled Plasma Optical
Emission Spectrometer (ICP OES) analysis was used to determine the concentrations
of metals present in the ferrite, which reached 6.5% (w/w) of Co. The optimal
conditions for discoloring the dye were evaluated using a factorial design. Using
CoFe2O4 as a catalyst, the best conditions for catalytic reaction were pH 3, 30.0
mg of catalyst, and 8.0 mL of H2O2 73% (v/v). Discoloration efficiencies of 87.3%
and 87.7% were obtained from CoFe2O4-R and CoFe2O4-LIBs, respectively. Therefore,
CoFe2O4-LIBs proved to be an efficient catalyst for discoloring MB dye using
heterogeneous photo-Fenton reactions. This work is of scientific, social,
economic, and environmental interest. It investigates the process of
synthesizing,characterizing CoFe2O4LIBs and the efficiency of degrading MB dye,
subjects that have economic and environmental, and therefore, social interest.
The work has scientific interest particularly because of the correlation between
the structure of the recycled material and its catalytic properties.
PMID- 28505576
TI - Toxicity of environmentally realistic concentrations of chlorpyrifos and
terbuthylazine in indoor microcosms.
AB - Few studies have been conducted into the evaluation of environmentally realistic
pesticide mixtures using model ecosystems. In the present study, the effects of
single and combined environmentally realistic concentrations of the herbicide
terbuthylazine and the insecticide chlorpyrifos were evaluated using laboratory
microcosms. Direct toxic effects of chlorpyrifos were noted on copepod nauplii
and cladocerans and the recovery of the latter was likely related with the
decrease observed in rotifer abundances. Terbuthylazine potentiated the effect of
chlorpyrifos on feeding rates of Daphnia magna, presumably by triggering the
transformation of chlorpyrifos to more toxic oxon-analogs. Possible food-web
interactions resulting from multiple chemical (and other) stressors likely to be
present in edge-of-field water bodies need to be further evaluated.
PMID- 28505577
TI - Evaluation of the photooxidation efficiency of As(III) applying the UVC/oxalate
technique.
AB - In this study, the photooxidation capacity of UVC/Oxalate (Ox) was evaluated
using As(III) as a typical pollutant. The results show that the direct oxidation
amount of As(III) induced by UVC in water was negligible, but the presence of Ox
remarkably accelerated the oxidation rate of As(III). Under UVC irradiation, 50
MUM As(III) can be completely oxidized to As(V) in the case of Ox concentration
above 300 MUM within 60 min. As(III) oxidation was found greatly related with the
photodecomposition of Ox. Much more Ox can be mineralized in more acidic
solution. At the same time, the photooxidation of As(III) was significantly
favored at decreased initial pH from 8.0 to 3.0. In this reaction system, the
role of oxygen was indispensable for Ox photodecomposition and As(III)
photooxidation, which can be ascribed to its special roles as a precursor of
reactive superoxide and an electron acceptor. In oxygen-present atmosphere, the
in situ production of H2O2 was detected during the photolysis of Ox and its
photolysis product, i.e., OH primarily contributed to the oxidation of As(III).
However, the photodecomposition of Ox and photooxidation of As(III) were
significantly inhibited in the anaerobic environment. In general, the homogeneous
photolysis of Ox in many commonly practiced UVC oxidation processes can be also
proposed as a supplementary method of generating highly oxiditive species in
aerobic condition.
PMID- 28505578
TI - The use of reactive index of hydroxyl radicals to investigate the degradation of
acid orange 7 by Fenton process.
AB - This study suggested the amount of hydroxyl radicals (OH) reacting with organics
as a new index to evaluate the reaction efficiency (RE) of Fenton process, and
used it to investigate the degradation mechanism of target pollution, Acid Orange
7 (AO7). The effects of initial concentrations of Fe(II), H2O2, and AO7 on RE
were quantified by using response surface methodology (RSM). The main factors
affecting RE were Fe(II), H2O2, and their interaction, and their percentage
effects were 65.75, 11.99 and 22.23%, respectively. Moreover, based on the
analysis result of RSM, a condition for good RE was proposed that it should
ensure a higher amount of OH reacted with organics, and reduce the amount of OH
scavenged by Fe(II). Liquid chromatography-mass spectrometry (LC/MS) analysis was
used to identify the products of AO7 degradation in Fenton process, and there
were three possible mechanisms to be observed, such as azo bond cleavage,
hydroxylation, and oxidation of naphthalene ring. The trend of mechanisms might
vary with the amount of OH attacks, and therefore the use of estimated RE could
provide more particular information to better understand the relationship between
organic degradation and OH attacks.
PMID- 28505579
TI - Effect of Lupinus albus L. root activities on As and Cu mobility after addition
of iron-based soil amendments.
AB - Arsenic and Cu mobility was investigated in the rhizosphere of Lupinus albus L.
grown in an iron-amended contaminated soil. White lupin was grown in rhizobags in
contaminated soil either left untreated or amended with iron sulphate plus lime
(Fe + lime) or biochar (Fe + BC). Porewater was monitored in rhizosphere and bulk
soil throughout the experiment and the extractable fraction of several elements
and As and Cu plant uptake was analysed after 48 days. The distribution of As,
Cu, P and Fe in the lupin rhizosphere was evaluated with chemical images obtained
by laser ablation-ICP-MS analysis of diffusive gradients in thin films (DGT)
gels. The treatments effectively reduced the soluble and extractable As and Cu
fractions in the bulk soil, but they did not affect plant uptake. In all cases,
soluble As was slightly enhanced in the rhizosphere. This difference was more
pronounced in the Fe + lime-treated rhizosphere soil, where an increase of pH as
well as extractable As and Fe concentrations were also observed. Chemical imaging
of the lupin rhizosphere also showed slightly higher As- and Fe-DGT fluxes around
lupin roots grown in the non-amended soil. Our findings indicate As and Fe co
solubilisation by lupin root exudates, likely as a response to P deficiency.
Arsenic mobilisation occurred only in the rhizosphere and was not decreased by
the amendments.
PMID- 28505580
TI - Factors affecting perceived change in physical activity in pregnancy.
AB - OBJECTIVE: reduction of physical activity (PA) during pregnancy is common but
undesirable, as it is associated with negative outcomes, including excessive
gestational weight gain. Our objective was to explore changes in five types of
activity that occurred during pregnancy and the behavioural determinants of the
reported changes in PA. DESIGN: we performed a secondary analysis of a cross
sectional survey that was constructed using the ASE-Model - an approach to
identifying the factors that drive behaviour change that focuses on Attitude,
Social influence, and self-Efficacy. PARTICIPANTS: 455 healthy pregnant women of
all gestational ages, receiving prenatal care from midwifery practices in the
Netherlands. FINDINGS: more than half of our respondents reported a reduction in
their PA during pregnancy. The largest reduction occurred in sports and brief
rigorous activities, but other types of PA were reduced as well. Reduction of PA
was more likely in women who considered themselves as active before pregnancy,
women who experienced pregnancy-related barriers, women who were advised to
reduce their PA, and multiparous women. Fewer than 5% increased their PA.
Motivation to engage in PA was positively associated with enjoying PA. KEY
CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: all pregnant women should be informed
about the positive effects of staying active and should be encouraged to engage
in, or to continue, moderately intensive activities like walking, biking or
swimming. Our findings concerning the predictors of PA reduction can be used to
develop an evidence-based intervention aimed at encouraging healthy PA during
pregnancy.
PMID- 28505581
TI - Spatiotemporal reorganization of the reading network in adult dyslexia.
AB - Developmental dyslexia is characterized by impairments in reading fluency and
spelling that persist into adulthood. Here, we hypothesized that high-achieving
adult dyslexics (i.e., university students with a history of dyslexia) manage to
cope with these deficits by relying to a greater extent on morphological
information than do non-impaired adult readers. We used magnetoencephalography
(MEG) in a primed lexical decision task, in which we contrasted orthographic,
morphological and semantic processing. Behavioral results confirmed that adult
dyslexics did indeed rely to a greater extent on the semantic properties of
morphemes than controls. In line with this, MEG results showed early
morphological effects (100-200 msec) in a frontal network, which reflected the
contribution of semantic processing. The same effects occurred much later in
controls (~400 msec). In contrast, controls showed early orthographic priming
effects in posterior left inferior temporal gyrus (LITG) at around 130 msec,
which were not seen in dyslexics. In the LITG, dyslexics showed only late
activation of semantic and orthographic information. The present results suggest
a spatiotemporal reorganization of the reading network, in which morphological
information located in frontal regions is activated earlier in high-achieving
adults dyslexics than controls.
PMID- 28505582
TI - Plastic potential: how the phenotypes and adaptations of pathogens are influenced
by microbial interactions within plants.
AB - Predicting the effects of plant-associated microbes on emergence, spread, and
evolution of plant pathogens demands an understanding of how pathogens respond to
these microbes at two levels of biological organization: that of an individual
pathogen and that of a pathogen population across multiple individual plants. We
first examine the plastic responses of individual plant pathogens to microbes
within a shared host, as seen through changes in pathogen growth and
multiplication. We then explore the limited understanding of how within-plant
microbial interactions affect pathogen populations and discuss the need to
incorporate population-level observations with population genomic techniques.
Finally, we suggest that integrating across levels will further our understanding
of the ecological and evolutionary impacts of within-plant microbial interactions
on pathogens.
PMID- 28505583
TI - Immunity and starvation: new opportunities to elevate disease resistance in
crops.
AB - Plants use multiple mechanisms to defend themselves against invading microbes.
Besides using their immune system to surveil and eliminate pathogens, plants
actively block the pathogens' access to nutrients as an alternative way to
prevent colonization. In this review, we focus on immunity and starvation as
major obstacles for pathogens' adaptation. We summarize the key mechanisms
employed by pathogens to modulate host immunity and to guarantee sugar uptake. In
contrast to genes that deal with the immune system and show high levels of
plasticity, pathogen genes involved in sugar acquisition are highly conserved,
and may not have adapted to co-evolving interactions with the host. We propose a
model to assess the durability of different control strategies based on the
ability of pathogens to deal with host immunity or starvation. This analysis
opens new opportunities to elevate disease resistance in crops by reducing the
likelihood of pathogen adaptation.
PMID- 28505584
TI - Development of a gold nanoparticle-based universal oligonucleotide microarray for
multiplex and low-cost detection of foodborne pathogens.
AB - Bacterial foodborne diseases remain major threats to food safety and public
health, especially in developing countries. In this study a novel assay,
combining gold nanoparticle (GNP)-based multiplex oligonucleotide ligation-PCR
and universal oligonucleotide microarray technology, was developed for
inexpensive, specific, sensitive, and multiplex detection of eight common
foodborne pathogens, including Shigella spp., Campylobacter jejuni, Bacillus
cereus, Escherichia coli O157:H7, Listeria monocytogenes, Salmonella enterica,
Staphylococcus aureus, and Vibrio parahaemolyticus. The target fragments of the
eight pathogens were enriched by multiplex PCR and subjected to multiplex ligase
detection reaction. Ligation products were enriched and labeled with GNPs by
universal asymmetric PCR, using excess GNP-conjugated primers. The labeled single
stranded amplicons containing complementary tag sequences were captured by the
corresponding tag sequences immobilized on microarrays, followed by silver
staining for signal enhancement. Black images of microarray spots were visualized
by naked eyes or scanned on a simple flatbed scanner, and quantified. The results
indicated that this assay could unambiguously discriminate all eight pathogens in
single and multiple infections, with detection sensitivity of 3.3-85CFU/mL for
pure cultures. Microarray results of ninety-five artificially contaminated and
retail food samples were consistent with traditional culture, biochemical and
real-time PCR findings. Therefore, the novel assay has the potential to be used
for routine detection due to rapidity, low cost, and high specificity and
sensitivity.
PMID- 28505585
TI - Giant hepatocellular carcinoma with bone metastasis in a young adult, emerged
from pigmented adenoma with beta-Catenin activation: A case report.
AB - INTRODUCTION: Hepatocellular carcinomas (HCC) that are very large in size are a
very rare finding in young adult. The malignant transformation of a pigmented
hepatocellular adenoma (HCA) with beta-Catenin activation is a possible cause for
appearance of HCC. PRESENTATION OF CASE: We present the case of a 33-year-old
male with a huge HCC with bone metastasis, emerged from pigmented HCA with beta
Catenin activation. As a two-stage surgical procedure, a left hepatectomy
followed by a partial rib resection was performed. DISCUSSION: Giant
hepatocellular carcinomas mostly develop in non-cirrhotic livers and at time of
diagnosis an extrahepatic spread occurs in up to 15%. In the present case, the
progression from a benign HCA to malignant HCC was documented, as a unique
finding. Surgical resection is the only curative treatment and was successfully
performed in this case. CONCLUSION: Hepatobiliary surgery with resection of
metastases is the treatment with best long-term survival for patients with huge
HCC. Molecular characterization as well as pigmentation analysis is useful tools
for risk assessment of HCA.
PMID- 28505586
TI - Oscillatory magnetic brain activity is related to dissociative symptoms and
childhood adversities - A study in women with multiple trauma.
AB - BACKGROUND: Individuals with trauma-related disorders are complex and
heterogeneous; part of this complexity derives from additional psychopathology
like dissociation as well as environmental adversities such as traumatic stress,
experienced throughout the lifespan. Understanding the neurophysiological
abnormalities in Post-traumatic stress disorder (PTSD) requires a simultaneous
consideration of these factors. METHODS: Resting state magnetoencephalography
(MEG) recordings were obtained from 41 women with PTSD and comorbid depressive
symptoms, and 16 healthy women. Oscillatory brain activity was extracted for five
frequency bands and 11 source locations, and analyzed in relation to shutdown
dissociation and adversity-related measures. RESULTS: Dissociative symptoms were
related to increased delta and lowered beta power. Adversity-related measures
modulated theta and alpha oscillatory power (in particular childhood sexual
abuse) and differed between patients and controls. LIMITATIONS: Findings are
based on women with comorbid depressive symptoms and therefore may not be
applicable for men or groups with other clinical profiles. In respect to
childhood adversities, we had no reliable source for the early infancy.
CONCLUSION: Trauma-related abnormalities in neural organization vary with both
exposure to adversities as well as their potential to evoke ongoing shutdown
responses.
PMID- 28505587
TI - Dietary Bacillus subtilis-based direct-fed microbials alleviate LPS-induced
intestinal immunological stress and improve intestinal barrier gene expression in
commercial broiler chickens.
AB - This study investigated the effects of Bacillus subtilis-based probiotics on the
performance, modulation of host inflammatory responses and intestinal barrier
gene expression of broilers subjected to LPS challenge. Chickens were randomly
allocated to one of the 3 dietary treatment groups - control, antibiotic, or
probiotic. At 14days, half of the chickens in each treatment were injected with
LPS (1mg/kg body weight), and the other half injected with sterile PBS. Chickens
fed probiotics weighed significantly more than controls at 15days of age,
irrespective of immune challenge. LPS challenge significantly reduced weight gain
at 24h post-injection, and the probiotics did not alleviate the LPS-induced
reduction of weight gain. Serum alpha-1-AGP levels were significantly higher in
LPS-injected chickens, and probiotic supplementation significantly reduced their
levels. The percentages of CD4+ lymphocytes were significantly increased in
probiotic groups in the absence of immunological challenge but were reduced
during LPS challenge compared to controls. CD8+ lymphocytes were significantly
reduced in probiotic-fed birds. The LPS-induced increase in the expression of
cytokines IL8 and TNFSF15 was reduced by probiotic supplementation, and IL17F,
iNOS expression was found to be significantly elevated in probiotic-fed birds
subjected to LPS challenge. The reduced gene expression of tight junction
proteins (JAM2, occludin and ZO1) and MUC2 induced by LPS challenge was reversed
by probiotic supplementation. The results indicate that B. subtilis-based
probiotics differentially regulate intestinal immune and tight junction protein
mRNA expression during states of LPS-mediated immunological challenge.
PMID- 28505588
TI - Hydroxylated 2-Ethylhexyl tetrabromobenzoate isomers in house dust and their
agonistic potencies with several nuclear receptors.
AB - In the current study, by combining ultra-high resolution (UHR) MS1 spectra, MS2
spectra, and derivatization, three hydroxylated isomers of 2-ethylhexyl
tetrabromobenzoate (OH-TBB) were identified in Firemaster(r) 550 and BZ-54
technical products. Also, a new LC-UHRMS method, using atmospheric pressure
chemical ionization (APCI), was developed for simultaneous analysis of OH-TBB,
TBB, hydroxylated bis(2-ethylhexyl)-tetrabromophthalate (OH-TBPH) and TBPH in 23
samples of dust collected from houses in Saskatoon, SK, Canada. OH-TBBs were
detected in 91% of samples, with a geometric mean concentration of 0.21 ng/g,
which was slightly less than those of OH-TBPH (0.35 ng/g). TBB was detected in
100% of samples of dust with a geometric mean concentration of 992 ng/g.
Significant (p < 0.001) log-linear relationships between concentrations of OH
TBBs, TBB, or OH-TBPHs and TBPH in dust support the hypothesis of a common source
of these compounds. OH-TBBs were found to be strong agonists of peroxisome
proliferator-activated receptor gamma (PPARgamma) and weaker agonists of the
estrogen receptor (ER), but no agonistic potencies was observed with the androgen
receptor (AR). Occurrence of OH-TBBs in technical products and house dust,
together with their relatively strong PPARgamma potencies, indicated their
potential risk to health of humans.
PMID- 28505589
TI - Multi-platform metabolomics and a genetic approach support the authentication of
agarwood produced by Aquilaria crassna and Aquilaria malaccensis.
AB - Agarwood, the resinous heartwood produced by some Aquilaria species such as
Aquilaria crassna, Aquilaria malaccensis and Aquilaria sinensis, has been
traditionally and widely used in medicine, incenses and especially perfumes.
However, up to now, the authentication of agarwood has been largely based on
morphological characteristics, a method which is prone to errors and lacks
reproducibility. Hence, in this study, we applied metabolomics and a genetic
approach to the authentication of two common agarwood chips, those produced by
Aquilaria crassna and Aquilaria malaccensis. Primary metabolites, secondary
metabolites and DNA markers of agarwood were authenticated by 1H NMR
metabolomics, GC-MS metabolomics and DNA-based techniques, respectively. The
results indicated that agarwood chips could be classified accurately by all the
methods illustrated in this study. Additionally, the pros and cons of each method
are also discussed. To the best of our knowledge, our research is the first study
detailing all the differences in the primary and secondary metabolites, as well
as the DNA markers between the agarwood produced by these two species.
PMID- 28505590
TI - Apoptosis induction activity and molecular docking studies of survivin siRNA
carried by Fe3O4-PEG-LAC-chitosan-PEI nanoparticles in MCF-7 human breast cancer
cells.
AB - Delivery of small interfering RNAs (siRNAs) into cells still remains a challenge
in gene delivery studies. Here, we investigated the ability of synthesized Fe3O4
PEG-LAC-chitosan-PEI nanoparticles for siRNA delivery of survivin as the model
gene into cells. The cellular uptake of survivin siRNA carried by synthesized
nanoparticles into MCF-7 breast cancer cell line was evaluated by florescent
microscopy and flowcytometry, both proving the efficacy of nanoparticles in
delivery of up to 64.7% in comparison with lipofectamine 2000. Furthermore, the
delivery of survivin siRNA by the nanoparticles (nanoplex) induced apoptosis that
was assessed through DAPI staining and Annexin V/PI assays. In addition, we
evaluated the efficacy of treatment with nanoplexes in the presence of
mitoxantrone, as a chemotherapeutic agent. Our data indicated that inhibition of
survivin expression increased the cell sensitivity to mitoxantrone. Real-time PCR
and western blotting analysis revealed a significant reduction in mRNA and
protein levels of survivin upon delivery of siRNA. Molecular docking studies
showed that nanoparticles can bind to centeral BIR domain of survivin, exactly
above zinc ion location with high affinity (DeltaG: -10.3Kcal/mol). Also,
thermodynamic studies proved the experimental results theoretically, revealing
that the siRNA-loaded nanoparticles have a suppressing effect on survivin mRNA.
Therefore, delivery of survivin siRNA into MCF-7 cells using Fe3O4-PEG-LAC
chitosan-PEI nanoparticles as a carrier enhances the cell death.
PMID- 28505591
TI - Factors associated with serum thyroglobulin in a Ukrainian cohort exposed to
iodine-131 from the accident at the Chernobyl Nuclear Plant.
AB - BACKGROUND: Serum thyroglobulin (Tg) is associated with the presence of thyroid
disease and has been proposed as a biomarker of iodine status. Few studies have
examined factors related to serum Tg in populations environmentally exposed to
ionizing radiation and living in regions with endemic mild-to-moderate iodine
deficiency. METHODS: We screened 10,430 individuals who were living in Ukraine
and under 18 years of age at the time of the 1986 Chernobyl Nuclear Power Plant
accident for thyroid disease from 2001 to 2003. We estimated the percent change
(PC) in serum Tg associated with demographic factors, iodine-131 thyroid dose,
and indicators of thyroid structure and function using linear regression. We also
examined these relationships for individuals with and without indications of
thyroid abnormality. RESULTS: Mean and median serum Tg levels were higher among
participants with abnormal thyroid structure/function. Percent change in serum Tg
increased among females, smokers and with older age (p-values<0.001), and Tg
increased with increasing thyroid volume, and serum thyrotropin (p-values for
trend<0.001). We found no evidence of significant associations between iodine-131
thyroid dose and Tg. Serum Tg levels were inversely associated with iodized salt
intake (PC=-7.90, 95% confidence interval: -12.08, -3.52), and over the range of
urinary iodine concentration, the odds of having elevated serum Tg showed a U
shaped curve with elevated Tg at low and high urinary iodine concentrations.
CONCLUSION: Serum Tg may be a useful indicator of population iodine status and a
non-specific biomarker of structural and functional thyroid abnormalities in
epidemiological studies.
PMID- 28505592
TI - Human norovirus inhibition by a human milk oligosaccharide.
AB - Human noroviruses are the leading cause of outbreaks of acute gastroenteritis.
Norovirus interactions with histo-blood group antigens (HBGAs) are known to be
important for an infection. In this study, we identified the HBGA binding pocket
for an emerging GII genotype 17 (GII.17) variant using X-ray crystallography. The
GII.17 variant bound the HBGA with an equivalent set of residues as the leading
pandemic GII.4 variants. These structural data highlights the conserved nature of
HBGA binding site between prevalent GII noroviruses. Noroviruses also interact
with human milk oligosaccharides (HMOs), which mimic HBGAs and may function as
receptor decoys. We previously showed that HMOs inhibited the binding of rarely
detected GII.10 norovirus to HBGAs. We now found that an HMO, 2'-fucosyllactose
(2'FL), additionally blocked both the GI.1 and GII.17 noroviruses from binding to
HBGAs. Together, these findings provide evidence that 2'FL might function as a
broadly reactive antiviral against multiple norovirus genogroups.
PMID- 28505593
TI - Foot-ankle complex injury risk curves using calcaneus bone mineral density data.
AB - OBJECTIVE: Biomechanical data from post mortem human subject (PMHS) experiments
are used to derive human injury probability curves and develop injury criteria.
This process has been used in previous and current automotive crashworthiness
studies, Federal safety standards, and dummy design and development. Human bone
strength decreases as the individuals reach their elderly age. Injury risk curves
using the primary predictor variable (e.g., force) should therefore account for
such strength reduction when the test data are collected from PMHS specimens of
different ages (age at the time of death). This demographic variable is meant to
be a surrogate for fracture, often representing bone strength as other parameters
have not been routinely gathered in previous experiments. However, bone mineral
densities (BMD) can be gathered from tested specimens (presented in this
manuscript). The objective of this study is to investigate different approaches
of accounting for BMD in the development of human injury risk curves. METHODS:
Using simulated underbody blast (UBB) loading experiments conducted with the PMHS
lower leg-foot-ankle complexes, a comparison is made between the two methods:
treating BMD as a covariate and pre-scaling test data based on BMD. Twelve PMHS
lower leg-foot-ankle specimens were subjected to UBB loads. Calcaneus BMD was
obtained from quantitative computed tomography (QCT) images. Fracture forces were
recorded using a load cell. They were treated as uncensored data in the survival
analysis model which used the Weibull distribution in both methods. The width of
the normalized confidence interval (NCIS) was obtained using the mean and +/- 95%
confidence limit curves. PRINCIPAL RESULTS: The mean peak forces of 3.9kN and
8.6kN were associated with the 5% and 50% probability of injury for the covariate
method of deriving the risk curve for the reference age of 45 years. The mean
forces of 5.4 kN and 9.2kN were associated with the 5% and 50% probability of
injury for the pre-scaled method. The NCIS magnitudes were greater in the
covariate-based risk curves (0.52-1.00) than in the risk curves based on the pre
scaled method (0.24-0.66). The pre-scaling method resulted in a generally greater
injury force and a tighter injury risk curve confidence interval. Although not
directly applicable to the foot-ankle fractures, when compared with the use of
spine BMD from QCT scans to pre-scale the force, the calcaneus BMD scaled data
produced greater force at the same risk level in general. CONCLUSIONS: Pre
scaling the force data using BMD is an alternate, and likely a more accurate,
method instead of using covariate to account for the age-related bone strength
change in deriving risk curves from biomechanical experiments using PMHS. Because
of the proximity of the calcaneus bone to the impacting load, it is suggested to
use and determine the BMD of the foot-ankle bone in future UBB and other loading
conditions to derive human injury probability curves for the foot-ankle complex.
PMID- 28505594
TI - The rheological behavior of a fast-setting calcium phosphate bone cement and its
dependence on deformation conditions.
AB - Calcium phosphate cements are osteoconductive biomaterials that are widely used
for bone repair and regeneration applications, including spinal fusion,
vertebroplasty, khyphoplasty, cranioplasty and periodontal surgeries. The flow
and deformation behavior (rheology) and injectability of the calcium phosphate
bone cements to the treatment site are governed by the setting kinetics of the
cement during which the initially flowable, viscous cement paste transforms into
a rigid elastic solid. Here time-dependent development of the linear viscoelastic
properties of a brushite-forming calcium phosphate cement are characterized and
linked to the mechanism and kinetics of the setting reaction and to the
injectability window available during the surgical applications of the cement.
The setting kinetics is shown to be a function of the deformation conditions that
are utilized in rheological characterization, emphasizing the intimate
relationships between setting kinetics, particle to particle network formation
and deformation history. Furthermore, the preshearing of the calcium phosphate
cement prior to injection and temperature are shown to alter the kinetics of the
setting reaction and thus to provide additional degrees of freedom for the
tailoring of the rheological behavior and injectability of the calcium phosphate
cement.
PMID- 28505595
TI - Epigenetic drug combination induces remission in mouse xenograft models of
pediatric acute myeloid leukemia.
AB - Aberrations in epigenetic modifications contribute to leukemogenesis in childhood
acute myeloid leukemia (AML). We combined DNA hypomethylating agent azacitidine
with histone deacetylase inhibitor panobinostat in preclinical models of
childhood AML. Synergistic cytotoxic effect upon treatment with azacitidine and
panobinostat with combination indices <1.0 was observed. Azacitidine and
panobinostat increased median survival by 26 and 6days respectively in MV4;11
xenografted mice. Mice treated with both drugs showed a drastic reduction in
leukemic burden leading to complete remission sustained for the duration of the
experimental period lasting more than 519days. Reduced leukemic burden and
prolonged survival was also observed in AML-193 xenografted mice treated with
azacitidine-panobinostat combination. Differential gene expression profiling was
performed on AML cells treated with azacitidine, panobinostat or azacitidine
panobinostat combination. Functional mapping of transcripts uniquely regulated by
the azacitidine-panobinostat combination in MV4;11 cells identified p53 as an
upstream regulator. A comparison of the uniquely modulated transcripts by
azacitidine-panobinostat combination in MV4;11 cells versus AML-193 and THP-1
cells, bearing mutated p53, also revealed p53 as the topmost upstream regulator.
Finally, expression of mutant p53 in MV4;11 cells reduced sensitivity to
azacitidine-panobinostat combination, suggesting that p53 may be a predictor of
response to epigenetic therapy in pediatric AML.
PMID- 28505596
TI - Engineered hydrogels increase the post-transplantation survival of encapsulated
hESC-derived midbrain dopaminergic neurons.
AB - Cell replacement therapies have broad biomedical potential; however, low cell
survival and poor functional integration post-transplantation are major hurdles
that hamper clinical benefit. For example, following striatal transplantation of
midbrain dopaminergic (mDA) neurons for the treatment of Parkinson's disease
(PD), only 1-5% of the neurons typically survive in preclinical models and in
clinical trials. In general, resource-intensive generation and implantation of
larger numbers of cells are used to compensate for the low post-transplantation
cell-survival. Poor graft survival is often attributed to adverse biochemical,
mechanical, and/or immunological stress that cells experience during and after
implantation. To address these challenges, we developed a functionalized
hyaluronic acid (HA)-based hydrogel for in vitro maturation and central nervous
system (CNS) transplantation of human pluripotent stem cell (hPSC)-derived neural
progenitors. Specifically, we functionalized the HA hydrogel with RGD and heparin
(hep) via click-chemistry and tailored its stiffness to encourage neuronal
maturation, survival, and long-term maintenance of the desired mDA phenotype.
Importantly, ~5 times more hydrogel-encapsulated mDA neurons survived after
transplantation in the rat striatum, compared to unencapsulated neurons harvested
from commonly used 2D surfaces. This engineered biomaterial may therefore
increase the therapeutic potential and reduce the manufacturing burden for
successful neuronal implantation.
PMID- 28505597
TI - An interpenetrating network-strengthened and toughened hydrogel that supports
cell-based nucleus pulposus regeneration.
AB - Hydrogel is a suitable scaffold for the nucleus pulposus (NP) regeneration.
However, its unmatched mechanical properties lead to implant failure in late
stage disc degeneration because of structural failure and implant extrusion after
long-term compression. In this study, we evaluated an interpenetrating network
(IPN)-strengthened and toughened hydrogel for NP regeneration, using dextran and
gelatin as the primary network while poly (ethylene glycol) as the secondary
network. The aim of this study was to realize the NP regeneration using the
hydrogel. To achieve this, we optimized its properties by adjusting the mass
ratios of the secondary/primary networks and determining the best preparation
conditions for NP regeneration in a series of biomechanical, cytocompatibility,
tissue engineering, and in vivo study. We found the optimal formulation of the
IPN hydrogel, at a secondary/primary network ratio of 1:4, exhibited high
toughness (the compressive strain reached 86%). The encapsulated NP cells showed
increasing proliferation, cell clustering and matrix deposition. Furthermore, the
hydrogel could support long-term cell retention and survival in the rat IVDs. It
facilitated rehydration and regeneration of porcine degenerative NPs. In
conclusion, this study demonstrates the tough IPN hydrogel could be a promising
candidate for functional disc regeneration in future.
PMID- 28505598
TI - Interlocked DNA topologies for nanotechnology.
AB - Interlocked molecular architectures are well known in supramolecular chemistry
and are widely used for various applications like sensors, molecular machines and
logic gates. The use of DNA for constructing these interlocked structures has
increased significantly within the current decade. Because of Watson-Crick base
pairing rules, DNA is an excellent material for the self-assembly of well-defined
interlocked nanoarchitectures. These DNA nanostructures exhibit sufficient
stability, good solubility in aqueous media, biocompatibility, and can be easily
combined with other biomolecules in bio-hybrid nano-assemblies. Therefore, the
study of novel DNA-based interlocked systems is of interest for nanotechnology,
synthetic biology, supramolecular chemistry, biotechnology, and for sensing
purposes. Here we summarize recent developments and applications of interlocked
supramolecular architectures made of DNA. Examples illustrating that these
systems can be precisely controlled by switching on and off the molecular motion
of its mechanically trapped components are discussed. Introducing different
triggers into such systems creates molecular assemblies capable of performing
logic gate operations and/or catalytic activity control. Interlocked DNA-based
nanostructures thus represent promising frameworks for building increasingly
complex and dynamic nanomachines with highly controllable functionality.
PMID- 28505599
TI - A new method for quantifying the performance of EEG blind source separation
algorithms by referencing a simultaneously recorded ECoG signal.
AB - Blind source separation (BSS) algorithms extract neural signals from
electroencephalography (EEG) data. However, it is difficult to quantify source
separation performance because there is no criterion to dissociate neural signals
and noise in EEG signals. This study develops a method for evaluating BSS
performance. The idea is neural signals in EEG can be estimated by comparison
with simultaneously measured electrocorticography (ECoG). Because the ECoG
electrodes cover the majority of the lateral cortical surface and should capture
most of the original neural sources in the EEG signals. We measured real EEG and
ECoG data and developed an algorithm for evaluating BSS performance. First, EEG
signals are separated into EEG components using the BSS algorithm. Second, the
EEG components are ranked using the correlation coefficients of the ECoG
regression and the components are grouped into subsets based on their ranks.
Third, canonical correlation analysis estimates how much information is shared
between the subsets of the EEG components and the ECoG signals. We used our
algorithm to compare the performance of BSS algorithms (PCA, AMUSE, SOBI, JADE,
fastICA) via the EEG and ECoG data of anesthetized nonhuman primates. The results
(Best case >JADE = fastICA >AMUSE = SOBI >= PCA >random separation) were common
to the two subjects. To encourage the further development of better BSS
algorithms, our EEG and ECoG data are available on our Web site
(http://neurotycho.org/) as a common testing platform.
PMID- 28505600
TI - God imagery and affective outcomes in a spiritually integrative inpatient
program.
AB - Religion and/or spirituality (R/S) can play a vital, multifaceted role in mental
health. While beliefs about God represent the core of many psychiatric patients'
meaning systems, research has not examined how internalized images of the divine
might contribute to outcomes in treatment programs/settings that emphasize
multicultural sensitivity with R/S. Drawing on a combination of qualitative and
quantitative information with a religiously heterogeneous sample of 241 adults
who completed a spiritually integrative inpatient program over a two-year period,
this study tested direct/indirect associations between imagery of how God views
oneself, religious comforts and strains, and affective outcomes (positive and
negative). When accounting for patients' demographic and religious backgrounds,
structural equation modeling results revealed: (1) overall effects for God
imagery at pre-treatment on post-treatment levels of both positive and negative
affect; and (2) religious comforts and strains fully mediated these links.
Secondary analyses also revealed that patients' generally experienced reductions
in negative emotion in God imagery over the course of their admission. These
findings support attachment models of the R/S-mental health link and suggest that
religious comforts and strains represent distinct pathways to positive and
negative domains of affect for psychiatric patients with varying experiences of
God.
PMID- 28505601
TI - The association between attempted suicide and stock price movements: Evidence
from Taiwan.
AB - This study is the first comprehensive analysis to investigate the potential
association between stock market fluctuations and attempted suicide events as
measured by self-inflicted injuries treated in hospitalization. Using nationwide,
15-year population-based data from 1998 through 2012, we observe that the
occurrences for the hospitalizations of attempted suicides are apparently
predicted by stock price movements. A low stock price index, a daily fall in the
stock index, and consecutive daily falls in the stock index have been shown to be
associated with increased risk of hospitalization in patients with attempted
suicide. More specifically, stock price index is found to be significant impact
on attempted suicide in the 45-54 age groups of both genders, whilst daily change
is significant for both genders in the 25-34 and 55-64 age groups and accumulated
change is only significant in female aged 25-44 and above 65. On the basis of the
results, relevant organizations should consider the suicidal factors that relate
prime-working-age and near-retirement-age people to better carry out specific
suicide prevention measures, and, meanwhile, encourage those people to pay less
attention towards daily stock price movements.
PMID- 28505603
TI - Icariin protects against thioacetamide-induced liver fibrosis in rats:
Implication of anti-angiogenic and anti-autophagic properties.
AB - BACKGROUND: Liver fibrosis is a major health problem. The current study evaluated
the potential of icariin (ICA) to guard against thioacetamide (TAA)-induced liver
fibrosis in rats. METHODS: Four groups of male rats were treated as follows:
group 1 was the control group, group 2 was given TAA (200mg/kg), group 3 was
administered ICA (50mg/kg) and TAA (200mg/kg), and group 4 was given ICA
(50mg/kg) alone. Animal treatment was continued for four weeks. RESULTS: Co
administration of ICA guarded against TAA hepatotoxicity as indicated by
significant inhibition in the rise of serum ALT and AST activities and albumin
concentrations. This was accompanied by inhibition of reduced glutathione
depletion, superoxide dismutase exhaustion, and lipid peroxide accumulation. In
addition, ICA inhibited the pathological alterations in liver architecture
induced by TAA. The antifibrotic activity of ICA was verified by reduced hepatic
collagen deposition in liver sections stained with Masson's trichrome and hepatic
Col-1alpha mRNA and hydroxyproline contents compared to the TAA-treated group.
The antiangiogenic activity of ICA was evidenced by lowered levels of mRNA of Ang
1 and protein expression of VEGF, PDGF-beta, and CTGF immunohistochemically.
Further, the anti-autophagic property of ICA was evidenced by amelioration of the
decrease in mTOR and p70S6 kinase expression and an increase in TLR4, NFkappaB,
IL1-beta, and COX-2 immunohistochemically. Moreover, ICA antagonized the increase
in HMGB1, TGF-beta, and Beclin-1 and the decrease in BAMBI hepatic mRNA levels.
CONCLUSIONS: ICA inhibits TAA-induced liver fibrosis in rats, possibly via
inhibition of angiogenesis and autophagy.
PMID- 28505602
TI - Unusual antigen presentation offers new insight into HIV vaccine design.
AB - Recent findings with a rhesus monkey cytomegalovirus based simian
immunodeficiency virus vaccine have identified strong CD8+ T cell responses that
are restricted by MHC-E. Also mycobacteria specific CD8+ T cells, that are MHC-E
restricted, have been identified. MHC-E therefore can present a wide range of
epitope peptides to CD8+ T cells, alongside its well defined role in presenting a
conserved MHC-class I signal peptide to the NKG2A/C-CD94 receptor on natural
killer cells. Here we explore the antigen processing pathways involved in these
atypical T cell responses.
PMID- 28505605
TI - Thickness and optical constants calculation for chalcogenide-alkali metal
Se80Te8(NaCl)12 thin film.
AB - Chalcogenide-alkali metal semiconducting thin films of four different thicknesses
of Se80Te8(NaCl)12 are deposited from bulk by thermal evaporation technique. The
crystallinity of the film improves with increasing of thickness as indicated by
the recorded X-ray diffraction patterns. The transmission and reflection spectra
are measured in the wavelength range of the incident photons from 250 to 2500nm.
The thickness and optical constants of the films are calculated based on
Swanepeol method using the interference patterns appeared in the transmission
spectra. It is found that the films have absorption mechanism which is an
indirect allowed transition. The effect of the film thickness on the refractive
index and the high-frequency dielectric constant are studied. With increasing the
film thickness, both the absorption coefficient and high-frequency dielectric
constant increase while the single-oscillator energy, optical band gap and
extinction coefficient decrease.
PMID- 28505604
TI - Nrf2 and NF-kappaB modulation by Plumbagin attenuates functional, behavioural and
biochemical deficits in rat model of neuropathic pain.
AB - BACKGROUND: Plumbagin is known to exhibit a broad range of biological activities
including anti-cancer, antimicrobial and has been widely used traditionally.
Nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-kappaB)
inhibitory and Nuclear factor (erythroid derived-2) like-2 (Nrf2) modulatory
activities of Plumbagin have been reported already. In nerve injury model of
neuropathy in rats, the role of NF-kappaB upregulation and declined antioxidant
defence has been well recognized. So, we evaluated neuroprotective potential of
Plumbagin in chronic constriction injury (CCI) of sciatic nerve induced
neuropathic pain in male Sprague-Dawley rats. METHODS: Animals were tested for
functional, behavioural and biochemical changes. Various markers associated with
oxidative stress and inflammatory changes were assessed in the sciatic nerve and
dorsal root ganglion (DRG) of the animals exposed to CCI mediated nerve injury.
RESULTS: CCI induced nerve injury led to long-lasting mechanical hyperalgesia,
loss of hind limb function and abnormal pain sensation. Plumbagin treatment (10
and 20mg/kg, po) significantly and dose-dependently reversed mechanical
hyperalgesia and other functional deficits. There was a marked increase in NF
kappaB and reduced Nrf2 levels in sciatic nerve and DRG following nerve injury.
Plumbagin strengthened the antioxidant defence by improving Nrf2 levels and
checked the neuroinflammation by decreasing NF-kappaB levels in sciatic nerve and
DRG. CONCLUSIONS: Together, these results suggested that Plumbagin alleviated CCI
induced neuropathic pain via antioxidant and anti-inflammatory mechanisms. Hence,
the study suggests that Plumbagin may be useful for the management of trauma
induced neuropathic pain.
PMID- 28505606
TI - A new azine derivative colorimetric and fluorescent dual-channel probe for
cyanide detection.
AB - A novel azine derivative colorimetric and fluorescent dual-channel probe
salicylaldehyde hydrazine-3,5-dibromosalicylaldehyde (1) has been designed,
synthesized and characterized. The probe 1 is confirmed to have especial
selectivity and good sensitivity on detecting CN- via UV-vis absorption and
fluorescence spectrum in aqueous solution (H2O/DMSO, 1:4, v/v). This colorimetric
and fluorescent dual-channel probe response to CN- owed to the deprotonation
process and established the mechanism by using 1H NMR spectroscopy. Further
researches showed that the detection limit of the probe 1 to CN- anions is
8.01*10-9M, significantly lower than the maximum level 1.9*10-6M in potable water
from WHO guidelines.
PMID- 28505607
TI - A flat acoustic lens to generate a Bessel-like beam.
AB - We report a flat acoustic lens with a periodical structure to transform a
divergent beam into a Bessel-like beam. Using the Schlieren imaging technique,
the propagation process of acoustic wave in the periodical structure was
experimentally observed. The pressure distribution in the main lobe is in good
agreement with the Bessel function and the positions of the side lobes are close
to the peak of the Bessel function. To observe the directivity of the beam,
simulations were performed using the finite-element method. The simulation
results indicated that the transmitted acoustic intensity at the central axis was
several times greater with the lens than without it. The applicability of the
lens for detecting the location of an acoustic source was also investigated.
PMID- 28505608
TI - A differential optical interferometer for measuring short pulses of surface
acoustic waves.
AB - The measurement of the displacements caused by the propagation of a short pulse
of surface acoustic waves on a solid substrate is investigated. A stabilized time
domain differential interferometer is proposed, with the surface acoustic wave
(SAW) sample placed outside the interferometer. Experiments are conducted with
surface acoustic waves excited by a chirped interdigital transducer on a
piezoelectric lithium niobate substrate having an operational bandwidth covering
the 200-400MHz frequency range and producing 10-ns pulses with 36nm maximum out
of-plane displacement. The interferometric response is compared with a direct
electrical measurement obtained with a receiving wide bandwidth interdigital
transducer and good correspondence is observed. The effects of varying the path
difference of the interferometer and the measurement position on the surface are
discussed. Pulse compression along the chirped interdigital transducer is
observed experimentally.
PMID- 28505609
TI - Disentanglement of Discordant Monochorionic Monoamniotic Twins in a Triplet
Pregnancy: An Innovative Approach Utilizing Fetoscopic Laser Coagulation with
Micro-Laparoscopic Scissor Dissection.
PMID- 28505610
TI - Predictors of Loss to Follow-Up among Children with Type 2 Diabetes.
AB - BACKGROUND/AIMS: Youth with type 2 diabetes (T2D) have poor compliance with
medical care. This study aimed to determine which demographic and clinical
factors differ between youth with T2D who receive care in a pediatric diabetes
center versus youth lost to follow-up for >18 months. METHODS: Data were analyzed
from 496 subjects in the Pe-diatric Diabetes Consortium registry. Enrollment
variables were selected a priori and analyzed with univariable and multivariable
logistic regression models. RESULTS: After a median of 1.3 years from enrollment,
55% of patients were lost to follow-up. The final model included age,
race/ethnicity, parent education, and estimated distance to study site. The odds
ratio (99% confidence interval) of loss to follow-up was 2.87 (1.34, 6.16) for
those aged 15 to <18 years versus those aged 10 to <13 years and 6.57 (2.67,
16.15) for those aged >=18 years versus those aged 10 to <13 years. Among
patients living more than 50 miles from the clinic, the odds ra tio of loss to
follow-up was 3.11 (1.14, 8.49) versus those living within 5 miles of the site.
CONCLUSION: Older adolescents with T2D are more likely to be lost to follow-up,
but other socioeconomic factors were not significant predictors of clinic follow
up.
PMID- 28505611
TI - Novel Insights in Fetal Cardiomyopathy due to in utero Herpes Simplex Virus
Infection.
AB - This is a case report of fatal cardiomyopathy in a fetus following maternal
intrauterine infection with herpes simplex virus (HSV), despite the mother having
no symptoms of an infection. The fetus showed signs of a disseminated infection
affecting the heart, brain, lungs, liver, adrenal glands, and skin. HSV
cardiomyopathy, characterized by vast necrosis, extensive calcifications, and
inflammatory infiltration, was found to be the cause of intrauterine fetal death.
To our knowledge, this is a unique report of an asymptomatic maternal nonprimary
or recurrent HSV infection that induced a transmission of HSV resulting in
extensive and fatal changes in the fetal heart.
PMID- 28505612
TI - Behavioral Performance and Neural Systems Are Robust to Sensory Injury in Workers
of the Ant Pheidole dentata.
AB - Miniaturized nervous systems have been thought to limit behavioral ability, and
animals with miniaturized brains may be less flexible when challenged by injuries
resulting in sensory deficits that impact the development, maintenance, and
plasticity of small-scale neural networks. We experimentally examined how
injuries to sensory structures critical for olfactory ability affect behavioral
performance in workers of the ant Pheidole dentata, which have minute brains
(0.01 mm3) and primarily rely on the perception and processing of chemical
signals and cues to direct their social behavior. We employed unilateral antennal
denervation to decrease the olfactory perception ability of workers and
quantified consequential neuroanatomical and behavioral performance effects.
Postablation neuroanatomical metrics revealed a 25% reduction in the volume of
the antennal lobe ipsilateral to the antennal lesion relative to the
contralateral lobe, indicating atrophy of the input-deprived tissue. However,
antennectomy did not affect the volumes of the mushroom body or its
subcompartments or the number of mushroom body synaptic complexes
(microglomeruli) in either brain hemisphere. Synapsin immunoreactivity, however,
was significantly higher in the ipsilateral mushroom body calyces, which could
reflect presynaptic potentiation and homeostatic compensation in higher-order
olfactory regions. Despite tissue loss caused by antennal lesioning and resulting
unilateral sensory deprivation, the ability of workers to perform behaviors that
encompass the breadth of their task repertoire and meet demands for colony labor
remained largely intact. The few behavioral deficits recorded were restricted to
pheromone trail-following ability, a result that was expected due to the need for
bilateral olfactory input to process spatial odor information. Our macroscopic
and cellular neuroanatomical measurements and assessments of task performance
demonstrate that the miniaturized brains of P. dentata workers and their
sensorimotor functions are remarkably robust to injury-related size reduction and
remain capable of generating behaviors required to respond appropriately to
chemical social signals and effectively nurse immatures, as well as participate
in coordinated foraging.
PMID- 28505613
TI - To Prime or Not to Prime - Is That Still a Question? A Comment on the US
Guidelines on Growth Hormone and Insulin-Like Growth Factor-I Treatment in
Children and Adolescents.
PMID- 28505614
TI - Pulmonary Involvement in Adult Patients with Inborn Errors of Metabolism.
AB - Inborn errors of metabolism (IEM) are rare individually, but taken together, they
affect 1 in 1,000 people. Most of the disease becomes apparent at the pediatric
age; however, with the identification of late-onset forms, and with improved
survival, several of these conditions may be found in adults of all ages. While
the lung is not typically a primary site of clinical disease in patients with
IEM, in some of them it can be a significantly affected organ with associated
severe respiratory complications. Lung involvement can be a late- onset feature
of a complex multisystemic disease, but sometimes it can also be the only
manifestation of underlying IEM. The aim of this review is to focus on specific
IEM associated with lung disease in adults and to provide the reader with an
overview of the diagnostic workup, overall disease management, and specific
treatments for the respiratory manifestations. Clinical suspicion, early
recognition, prompt diagnosis, and appropriate care of the respiratory
manifestation are crucial, as they can affect both the life expectancy and the
quality of life of these patients.
PMID- 28505615
TI - Acute Disseminated Intravascular Coagulation after Oxaliplatin Infusion.
AB - Oxaliplatin is one of the most commonly used drugs for patients with colorectal
cancer. It has rarely been associated with disseminated intravascular coagulation
(DIC) with only 3 previously reported cases. In all those instances, the patients
had started receiving oxaliplatin, developed evidence of DIC during the course of
planned treatment, and recovered with supportive care. We report a case of a 71
year-old man with colorectal cancer treated successfully with an oxaliplatin
based regimen who had disease relapse after 3 years. When treated again with
oxaliplatin, he developed signs of an acute hypersensitivity reaction, and
eventually had signs and symptoms consistent with DIC despite appropriate
management. This case is unique in that a DIC reaction evolving from a
hypersensitivity reaction occurred after the patient had already tolerated the
drug years earlier. It suggests a possible immune-mediated etiology to this rare
occurrence that should be kept in mind while utilizing this commonly employed
drug.
PMID- 28505616
TI - Pleural Biopsies: Just Freeze It?
PMID- 28505617
TI - Ganglion Cell Complex in Early and Intermediate Age-Related Macular Degeneration:
Evidence by SD-OCT Manual Segmentation.
AB - PURPOSE: To evaluate ganglion cell layer (GCL) and ganglion cell complex (GCC)
thickness manually by spectral-domain optical coherence tomography in subjects
with early and intermediate age-related macular degeneration (AMD) in 12
locations on the horizontal meridian. METHODS: A total of 450 eyes (specifically,
246 eyes classified as having early/intermediate AMD plus 204 control eyes) were
studied. Mann-Whitney U and Kruskal-Wallis tests were used to compare values
between the healthy controls and the AMD group and also between the subgroups
under study. Diagnostic performance was also compared calculating the areas under
the receiver operating characteristic curve. RESULTS: The manual layer
segmentation showed clear boundaries between the GCL and the GCC. It was in the
temporal GCC that more changes were found. CONCLUSIONS: The GCC, especially in
the temporal region, allowed the discrimination of differences between various
subgroups that have faint variations as well as between early AMD and the first
signs of aging.
PMID- 28505618
TI - Use of Epinephrine in Patients with Drug-Induced Anaphylaxis: An Analysis of the
Beijing Pharmacovigilance Database.
AB - BACKGROUND: Few studies assessing the use of epinephrine in drug-induced
anaphylaxis (DIA) in the hospital setting are available. We utilized the Beijing
Pharmacovigilance Database (BPD) to evaluate the appropriateness of epinephrine
for DIA management. METHODS: DIA cases collected in the BPD from January 2004 to
December 2014 were adjudicated and analyzed for demographics, causative drugs,
clinical signs, outcomes, initial treatment, route, dosing, and cardiovascular
adverse events (CAE) of epinephrine. RESULTS: DIA was primarily caused by
antibiotics (38.4%), radiocontrast agents (11.9%), traditional Chinese medicine
injections (10.9%), and chemotherapeutic drugs (10.3%). Only 708 (59.5%) patients
received epinephrine treatment. Patients who received epinephrine were more
likely to experience wheezing (p < 0.001) and respiratory arrest (p < 0.001).
Among 518 patients with a complete record of the epinephrine administration
route, the percentage of patients receiving it by intramuscular (IM) injection,
subcutaneous (SC) injection, intravenous (IV) bolus injection, or IV continuous
infusion was 16.9, 31.5, 43.5, and 8.1%, respectively. Among the 427 patients
with a record of both the administration route and the dosing, an overdose was
more likely with IV bolus (94.1%) in contrast to IM injection (56.6%; p < 0.001)
or SC injection (43.7%; p < 0.001). Among the patients analyzed for CAE (n =
349), 17 patients accounted for 19 CAE, and 13 (76.5%) of these patients were
overdosed with epinephrine. CONCLUSION: Underuse, inappropriate IV bolus use, and
overdosing were the 3 major problems with epinephrine use in DIA in China.
Educational training for health care professionals on the appropriate use of
epinephrine in managing anaphylactic reactions is suggested.
PMID- 28505620
TI - Should Hidradenitis Suppurativa Be Included in Dermatoses Showing Koebnerization?
Is It Friction or Fiction?
AB - BACKGROUND: The etiology of hidradenitis suppurativa (HS) involves genetic and
environmental factors. Well-established associated systemic factors are obesity,
smoking, inflammation, and bacteria. Whether localized environmental factors such
as friction and pressure may also play a causative role is still unclear.
OBJECTIVE: To describe the possible Koebner phenomenon (KP) in HS. METHODS: The
case notes on 14 patients with typical HS and additional HS lesions in previously
uninvolved skin areas exposed to mechanical stress, e.g., on the abdomen at the
level of the waistband, were reviewed with regard to the clinical characteristics
of the cohort. RESULTS: All 14 patients (7 females) were obese with a mean BMI of
35.8 (range 30.1-45.0). All patients developed additional ectopic HS lesions at
the sites of friction on the convex abdomen. The ectopic lesions were clinically
and histopathologically similar to HS. CONCLUSION: Mechanical stress factors or
trauma play a role in obese patients with HS. It is suggested that these new
induced lesions fit the concept of the KP. This phenomenon seems to occur in the
so-called frictional furunculoid type of HS and may explain the unique
distribution at certain localizations on the body of this follicular cutaneous
eruption. Removal in an early stage of HS of external stress factors that can
lead to the KP should be part of the treatment, especially in obese patients.
PMID- 28505619
TI - Bone Marrow Mesenchymal Stem Cell Transplantation Increases GAP-43 Expression via
ERK1/2 and PI3K/Akt Pathways in Intracerebral Hemorrhage.
AB - BACKGROUND/AIMS: Intracerebral hemorrhage (ICH) occurs in hypertensive patients
and results in high rates of mortality and disability. This study determined
whether bone marrow mesenchymal stem cell (BMSC) transplantation affects axonal
regeneration and examined the underlying mechanisms after the administration of
PD98059 (p-ERK1/2 inhibitor) or/ and LY294002 (PI3K inhibitor). The hypothesis
that was intended to be tested was that BMSC transplantation regulates the
expression of growth-associated protein-43 (GAP-43) via the ERK1/2 and PI3K/Akt
signaling pathways. METHODS: Seventy-five male rats (250-280 g) were subjected to
intracerebral blood injection and then randomly received a vehicle, BMSCs,
PD98059 or LY294002 treatment. Neurological deficits were evaluated prior to
injury and at 1, 3 and 7 days post-injury. The expression of GAP-43, Akt, p-Akt,
ERK1/2, and p-ERK1/2 proteins was measured by western blot analysis. RESULTS:
BMSC transplantation attenuated neurological deficits 3-7 days post-ICH. The
expression of GAP-43 was increased 3 days following BMSC transplantation.
However, this increase was inhibited by either PD98059 or LY294002 treatment.
Treatment with both PD98059 and LY294002 was more effective than was treatment
with an individual compound. CONCLUSION: BMSC transplantation could attenuate
neurological deficits and activate axonal regeneration in this rat ICH model. The
protective effects might be associated with increased GAP-43 expression by
activating both the ERK1/2 and PI3K/Akt signaling pathways.
PMID- 28505621
TI - GnRHa Treatment of Cryptorchid Boys Affects Genes Involved in Hormonal Control of
the HPG Axis and Fertility.
AB - The gonadotropin-releasing hormone agonist (GnRHa; Buserelin) rescues fertility
during adulthood in the majority of high infertility risk cryptorchid boys
presenting with defective mini-puberty. However, the molecular events governing
this effect are not understood. We report the outcome of an RNA profiling
analysis of testicular biopsies from 4 operated patients who were treated with
GnRHa for 6 months versus 3 operated controls who were not treated. GnRHa induces
a significant transcriptional response, including protein-coding genes involved
in pituitary development, the hypothalamic-pituitary-gonadal axis, and
testosterone synthesis. Furthermore, we observed an increased abundance of long
noncoding RNAs (lncRNAs) participating in epigenetic processes, including AIRN,
FENDRR, XIST, and HOTAIR. These data are consistent with the hypothesis that
hypogonadotropic hypogonadism in boys with altered mini-puberty is the
consequence of a profoundly altered gene expression program involving protein
coding genes and lncRNAs. Our results point to molecular mechanisms that underlie
the ability of GnRHa to rescue fertility.
PMID- 28505623
TI - Effect of a Low-Rank Denoising Algorithm on Quantitative Magnetic Resonance
Imaging-Based Measures of Liver Fat and Iron.
AB - PURPOSE: This study aimed to assess the effect of a low-rank denoising algorithm
on quantitative magnetic resonance imaging-based measures of liver fat and iron.
MATERIALS AND METHODS: This was an institutional review board-approved, Health
Insurance Portability and Accountability Act-compliant, retrospective analysis of
42 consecutive subjects who were imaged at 3T using a multiecho gradient echo
sequence that was reconstructed using the multistep adaptive fitting algorithm to
obtain quantitative proton density fat fraction (PDFF) and R2* maps (original
maps). A patch-wise low-rank denoising algorithm was then applied, and PDFF and
R2* maps were created (denoised maps). Three readers independently rated the PDFF
maps in terms of vessel and liver edge sharpness and image noise using a 5-point
scale. Two other readers independently measured mean and standard deviation of
PDFF and R2* values for the original and denoised maps; values were compared
using intraclass correlation coefficients (ICCs) and mean difference analyses.
RESULTS: Qualitatively, the denoised maps were preferred by all 3 readers based
on image noise (P < 0.001) and by 2 of 3 readers based on vessel edge sharpness
(P < 0.001-0.99). No reader had a significant preference regarding liver edge
sharpness (P = 0.16-0.48). Quantitatively, agreement was near perfect between the
original and denoised maps for PDFF (ICC = 0.995) and R2* (ICC = 0.995) values.
Mean quantitative values obtained from the original and denoised maps were
similar for liver PDFF (7.6 +/- 7.7% vs 7.7 +/- 7.8%; P = 0.63) and R2* (52.9 +/-
40.3s vs 52.8 +/- 41.1 s, P = 0.74). CONCLUSIONS: Applying the low-rank denoising
algorithm to liver fat and iron quantification reduces image noise in PDFF and
R2* maps without adversely affecting mean quantitative values or subjective image
quality.
PMID- 28505624
TI - Spectral Computed Tomography Imaging of Gastric Schwannoma and Gastric Stromal
Tumor.
AB - : Gastric schwannomas (GSs) and gastrointestinal stromal tumors (GSTs) are
grossly similar submucosal neoplasms with different prognoses. We explored the
value of spectral computed tomography (CT) to distinguish between them. METHODS:
Patients diagnosed with GS or GST at Lanzhou University Second Hospital, China,
between May 2013 and June 2015 were included retrospectively. The subjects
underwent spectral CT examination before surgery and had histologically confirmed
diagnosis of GS or GST. RESULTS: Twelve patients with GS (3 men; 9 women; mean
[SD] age, 47.0 [11.5] years) and 20 with GST (7 men; 13 women; mean [SD] age,
54.7 [9.9]) showed significant differences in terms of arterial phase (AP) at 70
keV (P < 0.001), portal phase (PP) at 70 keV (P = 0.002), AP iodine
concentration, PP iodine concentration, AP water concentration, AP slope of
spectral curve, and PP slope of spectral curve (all P < 0.001). CONCLUSIONS:
Spectral CT may be useful for noninvasive diagnosis of submucosal tumors.
PMID- 28505622
TI - Fat Suppressed Contrast-Enhanced T1-Weighted Dynamic Magnetic Resonance Imaging
at 3T: Comparison of Image Quality Between Spectrally Adiabatic Iversion Recovery
and the Multiecho Dixon Technique in Imaging of the Prostate.
AB - OBJECTIVE: To compare the quality of fat suppression and image quality between
multiecho Dixon technique (mDixon) and spectrally adiabatic iversion recovery
(SPAIR) in dynamic contrast-enhanced magnetic resonance imaging of the prostate.
METHODS: This prospective study assigned thirty consecutive patients to scanning
with SPAIR technique (SPAIR protocol) and another consecutive 30 patients to
scanning with mDixon technique (mDixon protocol). We calculated the contrast,
signal to noise ratio (SNR), contrast to noise ratio (CNR) and the coefficient of
variation between the 2 protocols. Two readers compared homogeneity of fat
suppression, image noise, image contrast, and image sharpness between the two
protocols. RESULTS: The SNR, CNR, and contrast of mDixon protocol were
significantly higher than those of the SPAIR protocol (SNR: 14.7 +/- 4.1 vs 11.0
+/- 2.6; P < 0.05; CNR: 6.3 +/- 1.6 vs 0.5 +/- 1.5; P < 0.01; contrast: 4.4 +/-
1.4 vs 1.3 +/- 0.5; P < 0.01), whereas the coefficient of variation of mDixon
protocol was significantly lower than that of SPAIR protocol (34.7 +/- 15.5 vs
43.7 +/- 23.1, P < 0.01). In qualitative image analysis, the image scores for the
homogeneity of fat suppression, image noise, and image sharpness were
significantly higher with mDixon protocol than those with SPAIR protocol (P <
0.01). There was no significant difference in image contrast between 2 fat
suppression protocols (P > 0.05). CONCLUSIONS: In dynamic contrast-enhanced
magnetic resonance imaging of the prostate, mDixon technique improved the
homogeneity of fat suppression without degrade of image quality compared with
SPAIR technique.
PMID- 28505625
TI - Metal Artifact Reduction on Chest Computed Tomography Examinations: Comparison of
the Iterative Metallic Artefact Reduction Algorithm and the Monoenergetic
Approach.
AB - OBJECTIVE: The aim of the study was to compare iterative metallic artefact
reduction (iMAR) and monochromatic imaging on metal artifact reduction. MATERIALS
AND METHODS: Follow-up of 29 occluded pulmonary arteriovenous malformations was
obtained with dual-energy computed tomography with reconstruction of averaged
images using filtered back projection (group 1), iMAR (group 2), and creation of
high-energy monoenergetic images (group 3). Two types of coils had been used: (a)
nickel only (group A, n = 18) and (b) nickel and platinum (group B, n = 11).
RESULTS: Compared with group 1, groups 2 and 3 images showed significant
reduction in artifact severity. Compared with group 3, group 2 images showed less
artifacts on subjective (artifact severity score: P = 0.0118; score of visibility
of surrounding structures: P = 0.0056) and objective (artifact attenuation: P <
0.0001) analyses. In group A, there was no significant difference in artifact
severity between groups 2 and 3 images (P > 0.05). In group B, metal artifacts
were only significantly reduced in group 2 images. CONCLUSIONS: Iterative
metallic artefact reduction reduces metal artifacts more efficiently than
monoenergetic imaging.
PMID- 28505626
TI - Discrimination Between Patients With Alzheimer Disease and Healthy Subjects Using
Layer Analysis of Cerebral Blood Flow and Xenon Solubility Coefficient in Xenon
Enhanced Computed Tomography.
AB - OBJECTIVE: The aim of this study was to develop a method for discriminating
between patients with Alzheimer disease (AD) and healthy subjects using layer
analysis of cerebral blood flow (CBF) and xenon solubility coefficient (lambda)
in xenon-enhanced computed tomography (CT). METHODS: Xenon-enhanced CT was
performed on 27 patients with AD (81.7 [3.3] years old) and 15 healthy volunteers
(78.6 [4.0] years old) using a wide volume CT. For each subject, we created the
first- (surface) to sixth-layer images of CBF and lambda for the 6 viewing
directions (layer thickness, 5 mm). For the discriminant views, receiver
operating characteristic curves for the ratio of CBF to lambda were created to
identify patients with AD. RESULTS: For the third- and fourth-layer left lateral
views, which were designated as the discriminant views, areas under the receiver
operating characteristic curve were 96.8% and 97.4%, respectively. CONCLUSIONS:
With the use of the discriminant views obtained by xenon-enhanced CT, we could
effectively discriminate between patients with AD and healthy subjects using both
CBF and lambda.
PMID- 28505627
TI - Endothelial Damage Signals Refractory Acute Kidney Injury in Critically Ill
Patients.
AB - : Critically ill patients with acute kidney injury (AKI) are heterogeneous on
pathophysiology and prognosis. The role of endothelial damage in the pathogenesis
of refractory AKI has not been clarified. The aim was to determine if biomarkers
of endothelial damage, independently of the inflammatory insult on the kidney,
can predict recovery of acute kidney injury. METHODS: From the "Procalcitonin And
Survival Study" multicenter intensive care unit cohort, followed for 28 days
after admission, we included patients without chronic kidney disease, who
survived >24 h after admission and with plasma samples at admission available for
biomarker analysis. We defined AKI by the "Kidney Disease: Improving Global
Outcomes" guidelines and recovery of prior kidney function as alive for five
consecutive days after admission with no need for renal replacement therapy and
creatinine levels consistently below *1.5 the level before admission. We adjusted
models for age, gender, vasopressor treatment, mechanical ventilation and levels
of creatinine, procalcitonin, platelets, and bilirubin at admission. RESULTS: Of
a total 213 with AKI at admission, 99 recovered prior kidney function during
follow-up. Endothelial damage on admission, measured by Soluble Thrombomodulin
(sTM), was the strongest predictor of a reduced chance of recovery of prior
kidney function (sTM in the highest vs. three lower quartiles hazard ratio 0.39;
95% confidence interval 0.21-0.73, P = 0.003). In contrast, the degree of the
initial inflammatory insult on the kidney, measured by neutrophil gelatinase
associated lipocalin (NGAL), failed to predict this outcome (NGAL in highest vs.
three lower quartiles hazard ratio = 1.20; 95% CI 0.72-2.00; P = 0.48).
Procalcitonin, a specific marker of bacterial infection, was also associated with
the rate of recovery (PCT in highest vs. three lower quartiles hazard ratio =
0.59; 95% CI 0.36-0.98; P = 0.04). CONCLUSION: AKI patients with high levels of
sTM had a reduced chance of recovering prior renal function. Our findings support
disintegration of the endothelium as a critical point in the pathogenesis of AKI
that is refractory to treatment.
PMID- 28505628
TI - Markers of Intestinal Damage and their Relation to Cytokine Levels in Cardiac
Surgery Patients.
AB - OBJECTIVES: In patients undergoing cardiac surgery, both extracorporeal
circulation (ECC) and intraoperative mesenterial hypoperfusion may account for
increased cytokine levels and lead to postoperative gastrointestinal (GI)
symptoms. METHODS: We investigated levels of the intestinal damage markers
intestinal fatty acid binding protein (I-FABP in plasma [n = 72] and urine [n =
37]), citrulline (in plasma [n = 35]), and claudin-3 (in urine [n = 37]) in
patients undergoing aortic or mitral valve surgery with or without coronary
artery bypass grafting. Furthermore, the relationship between these markers and
the surgery-induced cytokine response was explored by measuring serial plasma
levels of tumor necrosis factor-alpha, interleukin (IL)-6, IL-8, and IL-10 (n =
35). Finally, the relationship between markers of intestinal damage and GI
symptoms (abdominal pain, ileus, vomiting, diarrhea, time to first defecation)
was assessed. RESULTS: Plasma and urinary I-FABP levels, and urinary claudin-3
levels peaked at the end of surgery, while citrulline levels were not influenced
by surgery. ECC duration correlated with plasma I-FABP levels (r = 0.31, P =
0.007). Plasma levels of all measured cytokines increased during surgery, with
peak levels observed either at the end of surgery or on the first postoperative
day. While ECC duration correlated with IL-6 and IL-8 release (r = 0.43, P = 0.01
and r = 0.36, P = 0.04 respectively), there was no direct relationship between I
FABP and claudin-3 levels and cytokine concentrations. No patients developed
significant GI or non-GI complications, and I-FABP and claudin-3 release appeared
not to be related to postoperative GI symptoms, although the incidence of these
symptoms may have limited a reliable assessment. CONCLUSIONS: Longer duration of
ECC is associated with a more pronounced release of intestinal injury markers and
inflammatory cytokines, but intestinal injury markers are not directly related to
the observed increase in cytokine levels or GI-symptoms. These findings indicate
that ECC duration contributes to the cytokine response observed in cardiac
surgery patients and that intestinal injury itself is not a causative factor for
this response.
PMID- 28505630
TI - MACRA: Big Fix or Big Problem?
PMID- 28505629
TI - Impacts and mitigation of excess diesel-related NOx emissions in 11 major vehicle
markets.
AB - Vehicle emissions contribute to fine particulate matter (PM2.5) and tropospheric
ozone air pollution, affecting human health, crop yields and climate worldwide.
On-road diesel vehicles produce approximately 20 per cent of global anthropogenic
emissions of nitrogen oxides (NOx), which are key PM2.5 and ozone precursors.
Regulated NOx emission limits in leading markets have been progressively
tightened, but current diesel vehicles emit far more NOx under real-world
operating conditions than during laboratory certification testing. Here we show
that across 11 markets, representing approximately 80 per cent of global diesel
vehicle sales, nearly one-third of on-road heavy-duty diesel vehicle emissions
and over half of on-road light-duty diesel vehicle emissions are in excess of
certification limits. These excess emissions (totalling 4.6 million tons) are
associated with about 38,000 PM2.5- and ozone-related premature deaths globally
in 2015, including about 10 per cent of all ozone-related premature deaths in the
28 European Union member states. Heavy-duty vehicles are the dominant contributor
to excess diesel NOx emissions and associated health impacts in almost all
regions. Adopting and enforcing next-generation standards (more stringent than
Euro 6/VI) could nearly eliminate real-world diesel-related NOx emissions in
these markets, avoiding approximately 174,000 global PM2.5- and ozone-related
premature deaths in 2040. Most of these benefits can be achieved by implementing
Euro VI standards where they have not yet been adopted for heavy-duty vehicles.
PMID- 28505631
TI - Cholesterol Evaluation in Young Adults: Absence of Clinical Trial Evidence Is Not
a Reason to Delay Screening.
PMID- 28505633
TI - Prevalence of Elevated Cardiovascular Risks in Young Adults.
PMID- 28505634
TI - Guideline: Insufficient evidence exists on screening for obstructive sleep apnea
in asymptomatic adults.
PMID- 28505632
TI - Missed Opportunities for Measles, Mumps, Rubella Vaccination Among Departing U.S.
Adult Travelers Receiving Pretravel Health Consultations.
AB - Background: Measles outbreaks continue to occur in the United States and are
mostly due to infections in returning travelers. Objective: To describe how
providers assessed the measles immunity status of departing U.S. adult travelers
seeking pretravel consultation and to assess reasons given for nonvaccination
among those considered eligible to receive the measles, mumps, rubella (MMR)
vaccine. Design: Observational study in U.S. pretravel clinics. Setting: 24 sites
associated with Global TravEpiNet (GTEN), a Centers for Disease Control and
Prevention-funded consortium. Patients: Adults (born in or after 1957) attending
pretravel consultations at GTEN sites (2009 to 2014). Measurements: Structured
questionnaire completed by traveler and provider during pretravel consultation.
Results: 40 810 adult travelers were included; providers considered 6612 (16%) to
be eligible for MMR vaccine at the time of pretravel consultation. Of the MMR
eligible, 3477 (53%) were not vaccinated at the visit; of these, 1689 (48%) were
not vaccinated because of traveler refusal, 966 (28%) because of provider
decision, and 822 (24%) because of health systems barriers. Most MMR-eligible
travelers who were not vaccinated were evaluated in the South (2262 travelers
[65%]) or at nonacademic centers (1777 travelers [51%]). Nonvaccination due to
traveler refusal was most frequent in the South (1432 travelers [63%]) and in
nonacademic centers (1178 travelers [66%]). Limitation: These estimates could
underrepresent the opportunities for MMR vaccination because providers accepted
verbal histories of disease and vaccination as evidence of immunity. Conclusion:
Of U.S. adult travelers who presented for pretravel consultation at GTEN sites,
16% met criteria for MMR vaccination according to the provider's assessment, but
fewer than half of these travelers were vaccinated. An increase in MMR
vaccination of eligible U.S. adult travelers could reduce the likelihood of
importation and transmission of measles virus. Primary Funding Source: Centers
for Disease Control and Prevention, National Institutes of Health, and the Steve
and Deborah Gorlin MGH Research Scholars Award.
PMID- 28505635
TI - Review: In children and adults, vitamin D3 supplementation reduces risk for acute
respiratory tract infection.
PMID- 28505636
TI - Review: In COPD, injectable polyvalent pneumococcal vaccines reduce risk for
community-acquired pneumonia.
PMID- 28505637
TI - In C difficile infection, adding IV bezlotoxumab to standard antibiotics reduced
recurrence at 12 weeks.
PMID- 28505638
TI - Review: After coronary DES, <= 6 mo and 1 y of dual-antiplatelet therapy do not
differ for CV events at 1 y.
PMID- 28505639
TI - Review: Targeting SBP lowering to < 140 mm Hg reduces MACE more than targeting
SBP to > 140 in hypertensive patients >= 65 y.
PMID- 28505640
TI - In older men with low testosterone levels and age-associated memory impairment,
testosterone did not improve memory.
PMID- 28505641
TI - Bariatric surgery improved HbA1c at 5 y more than intensive medical care alone in
obese patients with T2DM.
PMID- 28505642
TI - Review: Strategies to improve provider adoption and implementation of clinical
practice guidelines were assessed.
PMID- 28505643
TI - Review: Interventions improve hospital antibiotic prescribing and reduce hospital
stay but do not affect mortality.
PMID- 28505645
TI - Screening Colonoscopy to Prevent Colorectal Cancer Among Medicare Beneficiaries
Aged 70 to 79 Years.
PMID- 28505646
TI - Screening Colonoscopy to Prevent Colorectal Cancer Among Medicare Beneficiaries
Aged 70 to 79 Years.
PMID- 28505647
TI - Management of Acute and Recurrent Gout.
PMID- 28505648
TI - Management of Acute and Recurrent Gout.
PMID- 28505649
TI - Management of Acute and Recurrent Gout.
PMID- 28505650
TI - Patient-Centered Medical Homes and Adherence to Chronic Disease Medications.
PMID- 28505651
TI - Patient-Centered Medical Homes and Adherence to Chronic Disease Medications.
PMID- 28505652
TI - This Is Why.
PMID- 28505653
TI - Forbidden Topics.
PMID- 28505654
TI - The Clearing.
PMID- 28505655
TI - Leg Braces, Bronzed, in a Dusty Box.
PMID- 28505657
TI - Web Exclusives. Annals for Hospitalists Inpatient Notes - Predicting Codes-A
Future With Fewer In-Hospital Cardiac Arrests.
PMID- 28505658
TI - Web Exclusives. Annals Consult Guys - The Adult Survivor of Hodgkin Disease:
Falling Through the Cracks.
PMID- 28505661
TI - Why Aren't International Travelers Vaccinated for Measles?
PMID- 28505660
TI - Prevalence of Elevated Cardiovascular Risks in Young Adults: A Cross-sectional
Analysis of National Health and Nutrition Examination Surveys.
AB - Background: The 2013 cholesterol management guidelines from the American College
of Cardiology and American Heart Association (ACC/AHA) recommend lipid screening
in all adults older than 20 years to identify those at increased risk for
atherosclerotic cardiovascular disease (ASCVD). Statins may be considered for
patients with elevated 10-year risk (>5%) or a low-density lipoprotein
cholesterol (LDL-C) level of 4.92 mmol/L (190 mg/dL) or greater. Objective: To
describe the prevalence of elevated ASCVD risk among nondiabetic adults younger
than 50 years. Design: Cross-sectional. Setting: NHANES (National Health and
Nutrition Examination Survey), 1999 to 2000 through 2011 to 2012. Participants:
Adults aged 30 to 49 years without known ASCVD or diabetes. Measurements: 10-year
ASCVD risk was estimated by using the 2013 ACC/AHA ASCVD risk calculator.
Participants were subdivided by age, sex, and history of smoking and
hypertension. The percentages of adults in each subgroup with a 10-year ASCVD
risk greater than 5% and of those with an LDL-C level of 4.92 mmol/L (190 mg/dL)
or greater were estimated. Low-prevalence subgroups were defined as those in
which a greater than 1% prevalence of elevated cardiovascular risk could be ruled
out (that is, the upper 95% confidence bound for prevalence was <=1%). Results:
Overall, 9608 NHANES participants representing 67.9 million adults were included,
with approximately half (47.12%, representing 32 million adults) in low
prevalence subgroups. In the absence of smoking or hypertension, 0.09% (95% CI,
0.02% to 0.35%) of adult men younger than 40 years and 0.04% (CI, 0.0% to 0.26%)
of adult women younger than 50 years had an elevated risk. Among other subgroups,
0% to 75.9% of participants had an increased risk. Overall, 2.9% (CI, 2.3% to
3.5%) had an LDL-C level of 4.92 mmol/L (190 mg/dL) or greater. Limitation: No
information was available regarding cardiovascular outcomes. Conclusion: In the
absence of risk factors, the prevalence of increased ASCVD risk is low among
women younger than 50 and men younger than 40 years. Primary Funding Source:
None.
PMID- 28505662
TI - Asymmetries between convergence and divergence reveal tonic vergence is dependent
upon phasic vergence function.
AB - Horizontal vergence eye movements are controlled by two processes, phasic and
slow-tonic. Slow-tonic responses are hypothesized to be stimulated by the faster,
pulse-step neural output of the phasic system. This suggests that the general
behavior of each system should be similar; however, this relationship has yet to
be investigated directly. We characterize the relationship between phasic and
tonic vergence by quantifying directional asymmetries in the response properties
of each mechanism to the same disparity amplitudes. Four subjects viewed
symmetric steps in disparity dichoptically at 40 cm while eye movements were
recorded with infrared oculography. First- and second-order phasic and slow-tonic
convergence response properties increased linearly with disparity demand (p <
0.01), whereas divergence responses did not (p > 0.05). Phasic divergence
responses were slower than convergence (p = 0.012) and were associated with a
higher frequency of saccades (p < 0.001). The average rate of slow-tonic change
was correlated to the average peak velocity of phasic vergence at the same
vergence demand in both directions, r = 0.78, p < 0.0001. Clear directional
asymmetries were observed in phasic and tonic vergence responses. The response
properties of the slow-tonic mechanism varied directly with the peak velocity of
the complementary phasic system. These results provide empirical evidence of the
relationship between phasic and slow-tonic vergence, suggesting that the latter
depends on the motor function of the former, specifically the peak velocity. The
recruitment of additional oculomotor mechanisms, such as saccades, improved the
phasic response properties of the slower divergence mechanism but did not
directly influence the response behavior of the slow-tonic mechanism.
PMID- 28505663
TI - Possible role for recurrent interactions between expansion and contraction cells
in MSTd during self-motion perception in dynamic environments.
AB - Cortical area MSTd contains cells sensitive to the radial expansion and
contraction motion patterns experienced during forward and backward self-motion.
We investigated the open question of whether populations of MSTd cells tuned to
expansion and contraction interact through recurrent connectivity, which may play
important roles in postural control and resolving heading in dynamic
environments. We used a neural model of MSTd to generate predictions about the
consequences of different types of interactions among MSTd expansion and
contraction cells for heading signals produced in the case of self-motion in the
presence of a retreating object-a stimulus that recruits both expansion and
contraction MSTd cell populations. Human heading judgments from a psychophysical
experiment that we conducted were consistent only with the MSTd model that
contained recurrent connectivity within and between expansion and contraction
cell populations. The model and human heading judgments were biased in the
direction of the object motion when the object crossed the observer's future path
and biased in the opposite direction when the object did not cross the path. We
conclude that recurrent interactions among expansion and contraction cells in
MSTd provide a plausible mechanism to support robust self-motion through dynamic
environments.
PMID- 28505664
TI - Temporal brightness illusion changes color perception of "the dress".
AB - "The dress" has provoked intensive commentary among psychophysicists, especially
in relation to color vision. Researchers have shown that manipulating illuminance
cues can influence the perceived colors of the dress. Here we investigate whether
illusory shifts in brightness can shift color perception of the dress. Drifting
achromatic gratings with fast off and fast on shading profiles are known to give
an illusion of brightening or darkening, respectively. We superimposed rotating
sawtooth gratings on a series of dress images that morphed from extreme
white/gold through to blue/black. In a sample of 18 adults (11 with white/gold
dress percept and seven with blue/black percept), a two-alternative, forced
choice constant stimulus task measured the morphed image point at which each
observer was equally likely to categorize the dress as white/gold or blue/black
(the point of subjective equality or PSE). Despite manifest individual
differences in the PSE, the two sawtooth temporal profiles consistently changed
the perceived colors of the dress. Perceptual dimming shifted color
categorization toward blue/black whereas perceptual brightening shifted color
categorization toward white/gold. We conclude that color categorization is
influenced substantially by illusory shifts in brightness.
PMID- 28505665
TI - Visual wetness perception based on image color statistics.
AB - Color vision provides humans and animals with the abilities to discriminate
colors based on the wavelength composition of light and to determine the location
and identity of objects of interest in cluttered scenes (e.g., ripe fruit among
foliage). However, we argue that color vision can inform us about much more than
color alone. Since a trichromatic image carries more information about the
optical properties of a scene than a monochromatic image does, color can help us
recognize complex material qualities. Here we show that human vision uses color
statistics of an image for the perception of an ecologically important surface
condition (i.e., wetness). Psychophysical experiments showed that overall
enhancement of chromatic saturation, combined with a luminance tone change that
increases the darkness and glossiness of the image, tended to make dry scenes
look wetter. Theoretical analysis along with image analysis of real objects
indicated that our image transformation, which we call the wetness enhancing
transformation, is consistent with actual optical changes produced by surface
wetting. Furthermore, we found that the wetness enhancing transformation operator
was more effective for the images with many colors (large hue entropy) than for
those with few colors (small hue entropy). The hue entropy may be used to
separate surface wetness from other surface states having similar optical
properties. While surface wetness and surface color might seem to be independent,
there are higher order color statistics that can influence wetness judgments, in
accord with the ecological statistics. The present findings indicate that the
visual system uses color image statistics in an elegant way to help estimate the
complex physical status of a scene.
PMID- 28505666
TI - Acute Pancreatitis: How Soon Should We Feed Patients?
PMID- 28505667
TI - Early Versus Delayed Feeding in Patients With Acute Pancreatitis: A Systematic
Review.
AB - Background: Acute pancreatitis is among the most common and costly reasons for
hospitalization in the United States. Bowel rest, pain control, and intravenous
fluids are the cornerstones of treatment, but early feeding might also be
beneficial. Purpose: To compare length of hospital stay, mortality, and
readmission in adults hospitalized with pancreatitis who received early versus
delayed feeding. Data Sources: MEDLINE via Ovid, EMBASE, the Cochrane Library,
CINAHL, and Web of Science through January 2017. Study Selection: Two authors
independently reviewed and selected studies if they were randomized clinical
trials, included adults hospitalized with acute pancreatitis, and compared early
versus delayed feeding (<=48 vs. >48 hours after hospitalization). Data
Extraction: Two investigators independently extracted study data and rated risk
of bias using the Cochrane Collaboration tool. Data Synthesis: Eleven randomized
trials (8 peer-reviewed publications, 3 abstract-only presentations) that
included 948 patients were eligible. Seven trials (3 with low risk of bias)
enrolled patients with mild to moderate pancreatitis. Four trials (1 with low
risk of bias) included patients with predicted severe pancreatitis. Routes used
for early feeding included oral (4 studies), nasogastric (2 studies), nasojejunal
(4 studies), and oral or nasoenteric (1 study). Among patients with mild to
moderate pancreatitis, early feeding was associated with reduced length of stay
in 4 of 7 studies (including 2 of 3 with low risk of bias). Other outcomes were
heterogeneous and variably reported, but no study showed an increase in adverse
events with early feeding. Among patients with severe pancreatitis, limited
evidence revealed no statistically significant difference in outcomes between
early and delayed feeding. Limitation: Heterogeneity of feeding protocols and
outcomes, scant data, and unclear or high risk of bias in several studies.
Conclusion: Limited data suggest that early feeding in patients with acute
pancreatitis does not seem to increase adverse events and, for patients with mild
to moderate pancreatitis, may reduce length of hospital stay. Primary Funding
Source: None. (PROSPERO: CRD42015016193).
PMID- 28505668
TI - Postmalaria Neurologic Syndrome-Autoimmune Encephalitis With Anti-Voltage-Gated
Potassium-Channel Antibodies.
PMID- 28505670
TI - The Increasing Genetic and Phenotypical Diversity of Congenital Myasthenic
Syndromes.
PMID- 28505671
TI - MEGDEL Syndrome: Expanding the Phenotype and New Mutations.
PMID- 28505672
TI - ["Translational Research in Ophthalmology is Important!"]
PMID- 28505669
TI - Add-on Antidepressants in the Naturalistic Treatment of Schizophrenia Spectrum
Disorder - When, Who, and How?
AB - The aim of this study was to evaluate antidepressant add-on treatment within the
acute treatment of schizophrenia spectrum disorder patients. Antidepressant add
on was evaluated in 365 patients within a naturalistic multicenter study.
Patients with/without antidepressant add-on were compared regarding clinical and
treatment-related variables, response and remission, and remission of depressive
and negative symptoms. The efficacy of antidepressant add-on treatment was
furthermore analyzed applying marginal structure models. Twenty-three percent of
the patients received antidepressant add-on for a mean duration of 50.28 (33.42)
days. Patients with the diagnosis of a schizoaffective disorder, multiple illness
episodes, and a longer duration of their illness as well as those with
significantly fewer baseline positive symptoms, more negative and depressive
symptoms, more side effects, and less subjective well-being were augmented with
antidepressants. At discharge no significant effect of antidepressant add-on
treatment was observed in terms of a 25% improvement (p=0.2623), a 50%
improvement (p=0.3946), remission (p=0.0552), or remission of depressive
(p=0.6336) and negative symptoms (p=0.8756). Also, when analyzing marginal
structure models considering the diagnostic subgroups, no significant effect was
found. Add-on with antidepressants is common. A final recommendation in terms of
this strategy's efficacy cannot be given.
PMID- 28505673
TI - [HLA-B27 Positive Acute Anterior Uveitis - A Translational Perspective].
AB - Background HLA-B27 positive acute anterior uveitis is the most common type of
uveitis, and it is an autoimmune disease that can be triggered by infections. The
precise mechanism of the interaction between involved microbes (mostly gram
negative bacteria) and the host immune system is not clear. The disease probably
results from an imbalance between pro- and anti-inflammatory components. Project
description This article gives a compact overview about the current knowledge of
the clinic and the etiopathogenesis of acute anterior uveitis as a basis for
future research approaches. The goal of the current research is to classify the
cellular and molecular pathogenetic factors in acute anterior uveitis. In this
regard, a project on uveitis within the clinical research unit FOR 2240
"(Lymph)Angiogenesis and Cellular Immunity in Inflammatory Diseases of the Eye",
examines the hypothesis that dysregulation of regulatory cell populations and
anti-inflammatory cytokines, such as interleukin-10 (IL-10), might contribute to
the development of ocular autoimmunity following infections. The goal is to
establish new markers for individual susceptibility in the risk group of the HLA
B27 positive population, because only about 1% of the HLA-B27 positive population
will eventually develop acute anterior uveitis. Conclusions Translational
research approaches to identify predisposed risk groups from the HLA-B27
population could improve patient care both on a prophylactic and a therapeutic
level.
PMID- 28505674
TI - [Novel Adjuvant Therapy for Ocular Melanoma].
AB - Background Malignant melanoma is the most common cancer of the eye in adults that
originates either in the intra-ocular uveal tract or extra-ocular conjunctiva.
Although the primary tumor can be treated successfully, no effective therapy for
both metastatic conjunctival and uveal melanoma currently exits. Tumor-associated
lymphangiogenesis and immune cell infiltration play a pivotal role in the
development and therapeutic targeting of metastases. Project description Here, we
provide an overview of current translational research on lymphangiogenesis and
its therapeutic inhibition as well as modulation of immune cell infiltration by
passive and active immunotherapy in melanoma of the eye. Specifically, our
previous and ongoing work on lymphangiogenesis and immune cells in ocular
melanoma within the clinical research unit FOR 2240 "(Lymph)Angiogenesis and
Cellular Immunity in Inflammatory Diseases of the Eye" is summarized. Conclusions
Translational research on the modulation of tumor-associated lymphangiogenesis
and immune cell infiltration could provide novel targets for adjuvant therapy in
melanoma of the eye.
PMID- 28505675
TI - [Anti(lymph)angiogenic Strategies to Improve Corneal Graft Survival].
AB - Corneal transplantation (keratoplasty) is the most frequently performed form of
transplantation worldwide. A rejection reaction against the transplant is the
main complication occurring after transplantation in an already vascularized, so
called "high-risk" recipient eye. Our group has shown that clinically invisible
lymphatic vessels play a crucial role in the induction of a rejection reaction
against the corneal graft, and that anti-(lymph)angiogenic therapies in the mouse
model of keratoplasty can significantly improve transplant survival. The
underlying mechanisms, which improve transplant survival through anti
lymphangiogenic therapies have not been well understood. We assume that the
blockade of lymph vessel sprouting leads to a tolerance (and not to a simple
ignorance) of the transplant, in which the antigen-presenting cells are held
longer in the cornea and, thus, an immunomodulation of these cells occurs.
Therefore, an important goal of our project is to find out whether and when
transplant tolerance comes from a corneal anti-lymphangiogenic therapy. We assume
that the antigen-presenting cells will have a different maturity level and that
more tolerogenic effector cells (regulatory T cells, Tregs) develop in the
absence of lymphatic vessels. Current anti(lymph)angiogenic therapies have the
disadvantage that they are primarily effective on actively growing vessels. Most
patients who receive high-risk keratoplasty often present in the clinic with
already established, mature corneal blood and lymphatic vessels. At present,
there are no lymph vessel regressing strategies, and the mechanisms regulating
the maturation of the lymphatics are largely unknown. Therefore, our second goal
is to develop new strategies for the regression of existing, pathological
lymphatic vessels in the cornea. We are testing both destructive strategies, such
as photodynamic therapy and diathermy as well as strategies for the molecular
destabilization of the lymph vessel endothelium. Thus, our project identifies the
precise mechanisms by which anti-lymphangiogenic therapies improve transplant
survival, and we are developing new strategies to push back mature lymphatics in
the high-risk setting.
PMID- 28505677
TI - [Influence of Aging on Severity and Anti-Inflammatory Treatment of Experimental
Dry Eye Disease].
AB - Purpose Aging is an important factor in dry-eye disease that has not been studied
in the context of therapeutic measures. Aging-associated modifications of the
ocular immune system implicate that anti-inflammatory therapies may act
differently among younger individuals in terms of onset and effect of different
substances. The goal of this study was to determine differences in clinical
phenotype and topical anti-inflammatory therapy using a desiccating stress mouse
model. Methods An experimental dry-eye disease (desiccating stress model) was
induced in 12-week and 12-month-old female BALB/c mice. Topical therapy included
0.05% cyclosporine/F4H5 (Novaliq), F4H5, 0.05% cyclosporine (Restasis(r),
Allergan) and dexamethasone (Monodex(r), Thea Pharma) for 3 consecutive weeks. A
control group received no therapy whatsoever. Readout parameters included tear
secretion, corneal fluorescein staining at 5 timepoints and histological analysis
of goblet cell count at the end of the experiments. Results The older mice
demonstrated a significantly stronger dry eye phenotype than the younger mice.
Following therapy, the older mice responded to topical anti-inflammatory therapy
significantly later than the younger individuals. Regarding the different
substances used, cyclosporine/F4H5 showed a significantly faster decrease in
corneal fluoresceine staining after only 1 week of therapy in comparison to all
other groups. This substance was also superior regarding tear secretion and
goblet cell count in age matched groups and in comparison to younger mice.
Conclusions These experimental data support the implication that aging should be
considered as an important factor in daily clinical practice. Furthermore, the
differences found between substance classes, such as calcineurin antagonists and
steroids, as well as different drug formulations, should be considered in future
pre-clinical and clinical trials.
PMID- 28505676
TI - [New Therapeutic Approaches in Inflammatory Diseases of the Eye - Targeting
Lymphangiogenesis and Cellular Immunity: Research Unit FOR 2240 Presents Itself].
AB - Background Ophthalmology, principally, is a very successful subdiscipline in
medicine. Nonetheless, there are still unmet medical needs which necessitate
translational research. Methods The funding instrument of a Research Unit (RU) of
the German Research Foundation (DFG) is presented as exemplified by the RU 2240
at the Department of Ophthalmology at the University of Cologne. Results The
Research Unit integrates different research groups working on pathologic ocular
inflammation, macrophages/microglia and (lymph)angiogenesis to collaborate in a
synergistic way. Rotation positions allow young clinicians to rotate into
research labs for a defined period of time. A Research Unit is also a powerful
strategic tool to strengthen clinical and experimental ophthalmology at
individual medical faculties. Conclusions The funding instrument of a Research
Unit is highly suitable for fostering translational research in a medical
subdiscipline such as ophthalmology, supporting the next generation of
(clinician) scientists in ophthalmology and finding new cures for our patients.
PMID- 28505678
TI - Is the Correlation between Salivary Cortisol and Serum Cortisol Reliable Enough
to Enable Use of Salivary Cortisol Levels in Preterm Infants?
PMID- 28505679
TI - Achievement of Body Mass Index Specific Weight Gain Recommendations: Impact on
Preterm Birth in Twin Pregnancies.
PMID- 28505680
TI - The Role of Interleukin-6 and Interleukin-8 Circulating Cytokines in
Differentiating between Feeding Intolerance and Necrotizing Enterocolitis in
Preterm Infants.
PMID- 28505681
TI - Prenatal Care Adherence and Neonatal Intensive Care Unit Admission or Stillbirth
among Women with Gestational and Preexisting Diabetes Mellitus.
AB - OBJECTIVE: To determine if there was an association between prenatal care
adherence and neonatal intensive care unit (NICU) admission or stillbirth, and
adverse perinatal outcomes in women with preexisting diabetes mellitus (DM) and
gestational DM (GDM). MATERIALS AND METHODS: This is a retrospective cohort
study among women with DM and GDM at a Diabetes in Pregnancy Program at an
academic institution between 2006 and 2014. Adherence with prenatal care was the
percentage of prenatal appointments attended divided by those scheduled.
Adherence was divided into quartiles, with the first quartile defined as lower
adherence and compared with the other quartiles. RESULTS: There were 443 women
with DM and 499 with GDM. Neonates of women with DM and lower adherence had
higher rates of NICU admission or stillbirth (55 vs. 39%; p = 0.003). A
multivariable logistic regression showed that the lower adherence group had
higher likelihood of NICU admission (adjusted odds ratio: 1.61 [1.03-2.5]; p =
0.035). Those with lower adherence had worse glycemic monitoring and more
hospitalizations. Among those with GDM, most outcomes were similar between groups
including NICU admission or stillbirth. CONCLUSION: Women with DM with lower
adherence had higher rates of NICU admission and worse glycemic control. Most
outcomes among women with GDM with lower adherence were similar.
PMID- 28505682
TI - [Implementation of a Laparoscopic Simulation Training in Undergraduate Medical
Education - The Lubeck Toolbox-Curriculum].
AB - BACKGROUND: Simulation-based training has become increasingly relevant in
minimally invasive surgery (MIS). It is unclear whether or not the established
Lubeck Toolbox (LTB) Curriculum for the acquisition of basic MIS skills can be
implemented to supplement standard undergraduate education in surgery and how it
would be accepted. MATERIALS UND METHODS: Since 04/2015, students at the medical
school of the University of Lubeck have had the option to complete the highly
standardized and validated LTB Curriculum. It consists of six subsequent tasks
with pre-defined learning goals. Video tutorials allow for a self-educating
approach. The individual training progress is documented continuously as
scheduled by the curriculum. The program was evaluated in a standardized manner
using an established online platform for the evaluation of university courses at
the University of Lubeck. RESULTS: Between 04/2015 and 07/2016, 63 students
completed the LTB Curriculum. The general interest in a surgical specialty rose
from an average of 1.61 (SD 0.78) before to 1.12 after the curriculum. The
numbers of required repetitions for the training tasks 1 - 6 were median 24 (6 -
79), 23 (5 - 61), 7 (5 - 33), 15 (5 - 59), 16 (5 - 50), and 18 (7 - 48),
respectively. None of the 63 students terminated the curriculum prematurely. On
average, 4.35 (SD 1.58) hours per week were spent training with an overall
duration of 4.1 (SD 1.2) weeks required to go through the LTB Curriculum.
Evaluation results showed an overall rating of 1.0 (SD 0.17). The average
learning progress, didactics and structure of the curriculum were rated as 1.0
(SD 0.24), 1.14 (SD 0.36), and 1.0 (SD 0.24), respectively. The relevance for the
following study years and the future professional activity was reported to be 1.2
(SD 0.45) on average. CONCLUSION: As an addition to the regular undergraduate
program, the Lubeck Toolbox Curriculum was well accepted by many students.
Evaluation showed exceedingly positive results. Furthermore, the data suggest
that the LTB Curriculum may increase the interest in a surgical specialty among
medical students. This aspect seems to be relevant in times where surgeons should
make every effort to recruit young doctors for surgical residency.
PMID- 28505683
TI - Tranexamic Acid Effectively Reduces Blood Loss and Transfusion Rates during
Simultaneous Bilateral Total Knee Arthroplasty.
AB - Tranexamic acid (TXA) can reduce blood loss and decrease transfusion rates after
total knee arthroplasty (TKA). The purpose of our study was to evaluate the
efficacy of TXA in a homogenous, consecutive cohort of patients undergoing
simultaneous bilateral primary TKA. This was a retrospective study of 50
consecutive patients who underwent bilateral simultaneous primary TKA between
2011 and 2015. Of these, 20 patients received TXA and 30 patients did not receive
TXA and served as the control group. Primary outcome measurements were
intraoperative estimated blood loss, hemoglobin (Hb) and Hematocrit (Hct) levels
on postoperative day (POD) 1 and POD2, and blood transfusion rates. Secondary
outcomes included length of stay (LOS), knee flexion/extension range of motion
(ROM), and postoperative complications. There was no difference between groups
for preoperative Hb and Hct (all p > 0.05). The TXA group demonstrate higher Hb
levels at POD1 (11.7 in TXA vs. 10.4 controls; p < 0.001) and POD2 (10.5 in TXA
vs. 9.6 controls; p < 0.001), as well as higher Hct levels at POD1 (35.6 in TXA
vs. 32.1 controls; p < 0.001) and POD2 (31.9 in TXA vs. 29.3 controls; p <
0.001). There was less percentage variation in Hb levels in the TXA group from
preoperative to POD1 (17.7% in TXA vs. 25.7% controls; p < 0.0001) and POD2
(26.1% TXA vs. 31.8% controls; p = 0.019). Similarly, less percentage variation
in Hct levels in the TXA group from presurgery to POD1 (17.0% TXA vs. 25.7%
controls; p < 0.0001) and POD2 (25.0% TXA vs. 31.3% controls; p = 0.005). A total
of 23.3% of patients in the control group required transfusions compared with no
patients in the TXA (p = 0.044). There were no differences in LOS, knee ROM, or
number of complications. No thromboembolic events occurred. TXA in bilateral
simultaneous TKA effectively reduces blood loss, maintains postoperative Hb and
Hct levels, and significantly decreases blood transfusion rates. The level of
evidence is level III (therapeutic study).
PMID- 28505684
TI - Does Gender Influence How Patients Rate Their Patient Experience after Total Knee
Arthroplasty?
PMID- 28505686
TI - ?
PMID- 28505685
TI - [Weaning Unit of the University Medicine Greifswald - Institutional Structure and
Weaning Results from Prolonged Ventilation over 10 Years].
AB - The increasing importance of intensive care medicine including mechanical
ventilation has been accompanied by the demand of weaning opportunities for
patients undergoing prolonged mechanical ventilation. Consequently, specialised
clinical institutions, focusing on the weaning from mechanical ventilation, have
been established since the 1980 s.The present article illustrates the structural
development and results of such a specialised institution at the University
Medicine Greifswald, using data of 616 patients collected within the past ten
years (2006 - 2015). Across the years, a shift in the underlying disease leading
to mechanical ventilation can be found, with rising numbers of patients suffering
from pneumonia/sepsis and declining numbers of patients who underwent cardiac
surgery in advance. The days with mechanical ventilation outside (p = 0.004) and
within the investigated institution (p = 0.02) are significantly declining. The
percentage of successfully weaned patients increased from 62.7 % (2006 - 2010) to
77.3 % (2011 - 2015), p < 0.001. Consecutively, the percentage of patients who
remained mechanically ventilated decreased from 16.4 % to 9.6 % (p < 0.001) and
the share of in-hospital deceased patients significantly declined from 20.9 % to
13.0 % (p < 0.001). Furthermore, the one-year-survival after hospital discharge
in successful weaned patients was 72 percent. The present data, collected at the
University Medicine Greifswald are quite comparable to data of other German
institutions that are specialised on weaning from mechanical ventilation.
PMID- 28505687
TI - [Exacerbation of COPD].
AB - Acute worsenings of chronic obstructive pulmonary disease (COPD) were for a long
time regarded as transient deteriorations, although occasionally life
threatening. No connection to disease progression was recognized. Data emerging
during the last decade showed that patients had a considerably worse survival
outcome after severe exacerbations. This insight was consolidated in 2012 by a
large population-based cohort analysis. At present, severe exacerbations are
regarded as key risk factors for COPD disease progression. The present article
summarises the current knowledge on exacerbations of COPD, as delineated during
an expert workshop in February 2017. It comprises pathogenic mechanisms,
exacerbation triggers, the characteristics of frequent exacerbators, and the
predictors of worse survival outcome. The role of comorbidities is considered
more closely. The presentation of the pharmacotherapy of acute exacerbation is
supplemented by an overview of ventilatory support. Finally, pharmacological and
nonpharmacological preventive measures are summarised.
PMID- 28505688
TI - [Test Your Knowledge].
PMID- 28505690
TI - Incidence of Low-Grade Testicular Injury in Orchidectomy Specimens Post
testicular Torsion.
AB - INTRODUCTION: Following detorsion and orchidopexy for testicular torsion,
predominantly animal studies have reported a risk of autoimmune and reperfusion
injury to the contralateral testis. As a result, when testicular viability is
compromised, orchidectomy is readily performed. This practice increases the
likelihood of testes with potentially reversible injury being excised. We aim to
determine the incidence of such occurrences and review the available evidence for
and against early orchidectomy when testicular viability is doubtful. MATERIALS
AND METHODS: Data for a 15-year period from two pediatric institutions on
testicular torsion in children younger than 16 years were reviewed. Using a
previously published grading system, the orchidectomy specimens in this cohort
with early low-grade injury were analyzed. Low-grade injury suggests the
possibility of restitutio ad integrum implying restoration of exocrine and
endocrine function of the affected testes. RESULTS: Between both institutions,
222 scrotal explorations were performed for testicular torsion; 20 neonatal and
202 outside the neonatal period (age range [median]: 1-28 days [3 days] and 3
months-16 years [13 years], respectively). Of these scrotal explorations, 17
neonatal and 66 nonneonatal orchidectomies were required (85 vs. 33%,
respectively; p < 0.0001). From these orchidectomy specimens, 5 (6%) were found
to have low-grade injury. The ages of these five children ranged from 9 to 16
years (median 15, mean 13.6 years). Their symptom duration ranged from 8 to 37
hours (median 14, mean 18 hours) and two of these children had a preoperative
ultrasound documenting no flow to the testis. CONCLUSION: The finding of
histopathological features that may represent salvageability of a torted testis
occurs relatively rarely. Because of this possibility, appropriate intraoperative
steps to check for reperfusion must be undertaken prior to orchidectomy. More
evidence for the use of antioxidants and tunica albuginea decompression to
improve testes salvage rates is required. The potential for exocrine and
endocrine function if partial testicular atrophy occurs and the evidence for
contralateral autoimmune testicular damage in pre- and postpubertal males require
further investigation.
PMID- 28505689
TI - [Pain Management in Palliative Care].
AB - A consistent pain management together with treatment of dyspnoea belongs to the
main issues in symptom control in particular in palliative thoracic oncology.
Together with the medicamentous therapy the psychologic and social circumstances
of the affected patients have to be considered as factors influencing the
experience of pain. The therapeutic fundament according to the WHO guideline for
cancer pain is the opiate based medicamentous adjustment combined with non
opioids. In principle, this should be performed preferably orally, as simply as
possible, according to a fix drug schedule and individually adjusted to the
needed dosage. Breakthrough pain has to be treated with rapidly efficacious, non
retarded analgetics. The typical adverse reaction profile for opiates like
constipation and initial nausea should be considered prophylactically by applying
concurrent medication with adjuvants. Co-analgesic drugs like anticonvulsiva or
corticosteroids could support the analgetic effect and are used preferably in
case of neuropathic pain. Primary aim in analgesic therapy is to achieve the best
possible pain reduction and hence to safeguard quality of life.
PMID- 28505691
TI - Laparoscopic Pyloromyotomy: A Study of the Learning Curve.
AB - INTRODUCTION: Laparoscopic pyloromyotomy (LPM) is a minimally invasive surgical
technique used in pyloric stenosis treatment. This technique is safe, effective,
and does not show more complications than laparotomy. Nevertheless, this
technique requires an acquisition period to be optimally applied. This study
analyses the learning curve of LPM. MATERIALS AND METHODS: Seven surgeons were
retrospectively evaluated on their 40 first LPM. Patient data were recorded,
including peroperative data (operation length and complications) and
postoperative recoveries (renutrition, vomiting, and complications). The learning
curves were evaluated and each variable was compared with the different moments
of the learning curve. RESULTS: The mean operative time is 25 +/- 11 minutes. It
significantly decreases with the learning curve (p < 0.01). Ten procedures were
necessary to acquire the operative technics. However, postoperative complications
with a necessary redo procedure appear after the 10th patient. There is no
significant difference concerning long-term postoperative complications according
to the learning curve and to surgeons. The best results are recorded after the
20th patients. Hospital length of stay also decreases significantly after the
10th procedure. The recorded postoperative vomiting is independent to the
operative time as the ad libitum feedings recovery. CONCLUSION: The learning
curve of LPM is cut into three stages. Only 10 cases are needed to acquire the
gesture. Complications appear after this acquirement period.
PMID- 28505692
TI - Outcome after Hypospadias Repair: Evaluation Using the Hypospadias Objective
Penile Evaluation Score.
AB - INTRODUCTION: The Hypospadias Objective Penile Evaluation Score (HOPE-Score) is
a concise and reproducible way to describe hypospadias severity. We classified
boys undergoing primary hypospadias repair to determine the correlation between
the HOPE-Score and the severity of hypospadias first and the outcome after
surgery second. MATERIALS AND METHODS: Patients who underwent primary
hypospadias repair from 2005 to 2014 were identified. An independent physician
assessed retrospectively the HOPE-Score, using photographies of the patients
before, after primary surgery, and after all necessary surgeries. The correlation
between the HOPE-Score and the severity of hypospadias, on the one hand, and the
outcome after surgery, on the other hand, were analyzed. RESULTS: The HOPE-Score
was assessed preoperatively for 79 boys, postoperatively for 66, and after all
necessary surgeries for 21 patients. Mean HOPE-Score reached 30.2 +/- 5.9 before
surgery, 42.2 +/- 6.1 after primary surgery, and 43.7 +/- 3.4 after all necessary
surgeries. A significant correlation between the HOPE-Score and the severity of
hypospadias before surgery was observed. The boys with glanular hypospadias
scored significantly higher (36.3 +/- 5.4) than those with distal (29.6 +/- 4.4)
and proximal hypospadias (21.1 +/- 3.5). Furthermore, a significant correlation
between the HOPE-Score and the outcome after hypospadias repair was observed.
Patients who needed no reintervention after primary hypospadias repair scored
significantly higher postoperatively (45.1 +/- 5.4) than those who needed a
second (40.8 +/- 4.2) or more than two surgeries (36.9 +/- 7.4). CONCLUSION: The
HOPE-Score is a good system to assess the severity of hypospadias and the
cosmetic outcome after hypospadias repair.
PMID- 28505693
TI - Pediatric Surgery: Job or Vocation?
PMID- 28505694
TI - Acute Idiopathic Scrotal Edema: Systematic Literature Review.
AB - INTRODUCTION: Existing information on acute idiopathic scrotal edema relies on
small case series and textbooks. METHODS: We searched reports with no date
limits on acute idiopathic scrotal edema. RESULTS: Thirty-seven studies were
included. Sixteen case series addressed the prevalence of acute idiopathic
scrotal edema among males with acute scrotum: among 3,403 cases, the diagnosis of
acute idiopathic scrotal edema was made in 413 cases (12%). Twenty-four reports
addressed history, findings, management, and course of acute idiopathic scrotal
edema in 311 patients. The patients mostly ranged in age from 5 to 8 years,
presented with acute scrotal redness and swelling, associated or not with mild
pain. Ninety percent or more of the cases developed in patients without atopic
diathesis and were not preceded by inguinoscrotal surgery, acute febrile
illnesses, or trauma. They were afebrile; in good general condition; and
presented without pruritus, nausea or vomiting, or abdominal pain. The lesions
were bilateral in two-thirds and unilateral in one-third of the cases. The
condition resolved spontaneously within 2 to 3 days without sequelae.
Approximately 10% of the cases experienced a recurrence. CONCLUSION: Acute
idiopathic scrotal edema is a self-limiting condition that accounts for >= 10% of
cases of acute scrotum in children and adolescents.
PMID- 28505695
TI - The Status of Junior Pediatric Surgeons in Europe: Old Challenges, New
Opportunities.
PMID- 28505696
TI - [Can the "Rule of Rescue" be rescued? A comment on Weyma Lubbe's "Rule of Rescue
vs. Rescue of statistical life"].
AB - In her article "Rule of Rescue vs. Rescue of statistical lives" [1] Weyma Lubbe
elevates gut feelings supporting the "rule of rescue" to "civic judgments".
Without doubt in a constitutional democracy ultimately the judgments and
aspirations of citizens must be decisive. Yet, particularly in the field of
health policy, the bias to overemphasize what are closer rather than more remote,
concrete rather than abstract consequences, should be counteracted not supported.
The utility forgone by observing the "rule of rescue" in health care must be held
against it. Making the "opportunity costs" of applying the rule of rescue visible
is part of the citizens' "health ethic information package" and not as such an
attack on the "Rule of Rescue".
PMID- 28505697
TI - [The Development of Palliative Care Hospital Support Teams (HPCTs) in Bavaria
from 2011-2015: Tasks, Acceptance, Structure and Funding].
AB - INTRODUCTION: Palliative care hospital support teams (HPCTs) provide inpatients
from all departments palliative medical support. Seriously ill as well as dying
patients, who are being treated in facilities that do not have their own
palliative care unit, can benefit from these multi-professional teams just as
much as patients who do not (yet) need to be admitted to a palliative care unit.
At the end of 2015, 53 HPCTs, which were in accordance with the requirements
established in the "Program for HPCTs" by the Bavarian Ministry of Health in
2009, had been approved in Bavaria. METHODS: Using a questionnaire that was
distributed by mail (2011) and an online survey (2015), we asked all Bavarian
HPCTs, which had been approved up until then, to answer questions regarding their
tasks, the level of acceptance within their hospital, the structure of their
staff and funding. In addition to questions, which were rated on an applicability
scale from 0 to 10, there was also room for written comments. RESULTS: The return
rate in 2011 was 77% (17 questionnaires) and 53% (28) in 2015. In sum, HPCTs were
widely regarded as a suitable instrument for improving in-house palliative care
(2011: median 7.8 (0-10) +/-1.9, 2015: 7.2 (0-10) +/-2.3; n.s.). The level of
acceptance among the other departments of the hospital was assessed as being
significantly higher in 2015 (7.2+/-2.3) than it was 4 years earlier (5.7+/-2.2;
p<0.05). HPCTs cover various tasks, most commonly including "supportive
conversations," "accompaniment in the dying phase," "pain therapy" and "discharge
management." However, a decline in multi-professionalism within the teams could
be seen, especially in the fields of psychology/psycho-oncology and spiritual
care (p<0.05). Both surveys showed that an essential aspect in funding the teams
was the supplementary payment ZE 60 for "complex palliative medical treatments."
However, funding in general was predominantly reported as being quite difficult:
only 29% of the HPCTs of 2015 indicated that all of their costs were covered.
CONCLUSION: HPCTs in Bavaria take over important tasks in caring for seriously
ill and dying patients and their families. According to their own appraisal, the
level of acceptance within hospitals is improving. The hope is that new
regulations, such as the new OPS 8-98 h (specialized complex palliative
treatments provided by a HPCT), which was introduced in 2017, will solidify
funding without jeopardizing the multi-professionalism that characterizes HPCTs.
PMID- 28505698
TI - [Internet Use by Oncology Outpatients: Results of a Survey in Germany].
AB - Objective Internet has become an important source of information for cancer
patients regarding disease and treatment. A national survey was conducted to
assess the importance of Internet in the routine care of cancer patients in
Germany. Method The cross-sectional survey included 5,984 outpatients (56.7%
female, M=64.3 years, SD=12). 3 groups were identified: Internet users, non-users
whose families/friends did online research for them, and "complete" non-users.
The data was analyzed using descriptive statistics and group comparisons. Results
1 patient in 2 used the Internet to research health-related information. Internet
users considered this research to be helpful, felt better able to participate in
health-related decisions, and less alone with their disease. However, the
information found online contributed to a feeling of uncertainty. 72.5% of
Internet users researched treatment options and 21.3% talked to their doctor
about their research. Conclusion The Internet was shown to be an important source
of information for cancer patients. For patients to be able to use Internet
research meaningfully, it could be helpful that they receive support from their
oncologist.
PMID- 28505699
TI - [Psychological Stress in Hospital Nursing Staff: Effects of Status and
Organizational Structures].
AB - OBJECTIVE: The study investigates the impact of organizational structures in
hospitals on nursing staff's psychological stress. The stress level that is
caused by the specific working conditions of a major hospital is presented in a
cross-sectional analysis differentiated by organizational categories with regard
to effects of structure and status. METHODS: Data were collected via Impuls-Test
and by a context-specific supplementary questionnaire among the registered
nursing staff of a major maximum care hospital. For analysis of the data, we used
the effort-reward-imbalance and the job-demand-control model as well as an
average calculation of 13 different dimensions of working conditions,
differentiated by organizational categories. RESULTS AND CONCLUSION: The results
show that the nursing staff's level of psychological stress can only be
understood against the background of their organizational involvement and
position in the hospital. The effects clearly vary in terms of organizational
unit, working hour model and status and position occupied.
PMID- 28505700
TI - [The Role of Municipalities in Lower Saxony for Future Physician's Care - A
Survey of Mayors and District Administrators].
AB - BACKGROUND: Comprehensive outpatient medical care is being increasingly
threatened due to the decreasing willingness of physicians to establish their
practices in rural areas. Partly, municipalities feel impelled to support doctors
setting up their practices with their own resources. The aim of this study was to
get the community perspective on the ambulatory care situation and to examine the
role and influence of the local authorities. METHODS: The mayors (n=411) and
district administrators (n=38) in Lower Saxony received a self-developed written
questionnaire in September 2015 (comprehensive survey). RESULTS: The response
rate was 72%. Availability of general practitioners was considered as inadequate
by 30% of those surveyed and 71% described specialist care as being insufficient.
Two-thirds of respondents saw local problems with filling vacant doctors'
offices. 42% of mayors and 65% of district administrators said they had already
supported outpatient doctors. The most frequent measures carried out so far
included financial support, consulting services and the development of
cooperation and networks. The majority considered the model of medical care
centers being operated under municipal sponsorship to be unsuitable in principle.
CONCLUSIONS: Local governments prevalently see problems with filling vacant
doctors' offices as well as a need for local support. A significant proportion of
municipalities has already implemented various support measures. Community
participation in the outpatient care with medical care centers under municipal
sponsorship is assessed rather critically.
PMID- 28505701
TI - [Compatibility of Work and Family Life: Survey of Physicians in the Munich
Metropolitan Area].
AB - Aim Investigation of the compatibility of work and family life for physicians in
the Munich metropolitan area. Methods Survey of a representative sample of 1,800
physicians using a questionnaire. Results Men were less satisfied (7% very
satisfied vs. 21%) with compatibility between work and family life than women.
The group least satisfied overall was hospital-based physicians (p=0.000, chi
square=122.75). Women rather than men cut back their career due to children,
perceived their professional advancement as impaired, desisted from establishing
private practice or quit hospital employment altogether. Respondents strove for
flexible childcare and makeshift solution if the established service failed. Most
did not have that at their disposal. Hospital-based physicians wished for
predictable working hours, and would like to have a say in the structure of their
schedule. For the majority this was not the case. While for 80% it would be
important to participate in the definition of their working hours, this was only
possible in 17%. 86% found the opportunity to work part-time important, but many
doctors (more than 30%) did not have that option. The biggest help for office
based physicians would be an expedited procedure by the Bavarian Association of
Statutory Health Insurance Physicians (KVB) when applying for a proxy. The second
most important would be the ability to hand over on-call duties. 36% of
respondents felt that compatibility of work and family life was best achieved
outside of patient care, during residency 42% believed this to be the case. Only
6% of physicians felt the best compatibility to be achieved in a hospital. Among
the physician owners of practices, 34% considered their model to be the best way
to reconcile both aspects of life. Conclusion More flexible options for childcare
and more influence on the definition of working hours are necessary in order to
better reconcile work and family life. For office-based physicians it must be
made easier to find a substitute. Currently, especially women consider children
as hindering their careers. Hospitals are perceived as extremely unfavorable
workplaces for achieving compatibility between work and family life.
PMID- 28505702
TI - [Recalculation of Tobacco-Attributable Mortality: National and Regional Data for
Germany].
AB - Introduction Tobacco use accounts for about 5 million annual premature deaths
worldwide. Tobacco thus is the single most important preventable health risk. In
this paper we present a recalculation of tobacco-attributable mortality in
Germany, and examine gender and regional differences. Data and Methods The
calculation is based on the prevalence of current and former smokers, the
relative mortality risks for diseases for which tobacco use is associated with an
increased mortality risk, and the number of deaths by ICD-10 diagnoses. For the
first time, colorectal and liver cancer as well as type 2 diabetes and
tuberculosis were taken into consideration. Results In 2013, 121 087 deaths were
attributable to smoking (i. e. 13.5% of all deaths), including 84 782 deaths in
men and 36 305 deaths in women. The tobacco-attributable mortality rate was
higher in men than in women, and in terms of regional discrepancies a north-south
gradient was observed. Conclusion The number of tobacco-attributable deaths is
substantial and higher than previously predicted. Compared to 2007, numbers have
increased in absolute terms, whereas in relative terms the tobacco-attributable
mortality rate declined. Given processes of demographic aging, a continued rise
in absolute numbers of tobacco-attributable mortality is to be expected in the
future.
PMID- 28505703
TI - [Benefit and Sustainability of Networks for workplace Health Promotion in SME
Examined at the SME Networks "Bewegte Unternehmen" and "Vitale Unternehmen"].
AB - PURPOSE: The purpose of the study was to analyze if 2 regional networks of small
and medium enterprises (SME) for workplace health promotion are sustainable, and
to find out the motivation of the enterprises to join the network. It was also
examined if there is a stable culture of cooperation 6 -10 years after the
founding of the network. Additionally, the study checked the current work and
suggestions for improvement to the network structure, so that in the future,
promotion of workplace health can be further improved. METHOD: 2 regional
networks, founded in 2005 and 2009, were studied. Standardized telephone
interviews carried out between September 2013 and January 2014 enabled data
collection for this cross-sectional study. 42 interviews with 6 open questions
were organized with the managers of the companies or the person responsible for
workplace health promotion. RESULTS: The results of the study show that 88.1%
(n=37) of the network company members profited from the exchange of experiences.
50.0% (n=21) benefited from shared activities and 28.6% (n=12) from making new
contacts. 9.5% (n=4) of the respondents expressed concerns about excessive
bureaucracy resulting in too much effort for too little benefit and 7.1% (n=3)
were also missing comprehensive structural measures. Suggestions for improvement
were enhancement of practical work (26.2%, n=11) and the wish for stronger
commitment (11.9%, n=5). 90.5% (n=38) considered their expectations as fulfilled
and 66.7% (n=28) evaluated the current work as being quite positive. CONCLUSION:
The networks have turned out to be sustainable, proven by the fact that the
companies still are members of the networks for 6 and 10 years, respectively and
are still satisfied with the network. The study shows that the majority of the
members profits from the membership of these regional networks. Networks can help
them to implement permanent workplace health promotion. To further improve the
work of the network, a systematic and scientific workplace health promotion
scheme is recommended.
PMID- 28505704
TI - [Compilation of Second Opinion Programs in the German Statutory Health
Insurance].
AB - OBJECTIVE: According to a new legislation passed in 2016, patients with an
indication for elective procedures have the right to obtain a second opinion. The
Federal Joint Committee has not yet provided a list of indications that this
legislation will cover. Independently of this, the statutory health insurances
can, nonetheless, pay for a second opinion. The aim of this article is to give an
overview of current second opinion programs delivered by the statutory health
insurance schemes. METHODS: Websites of all German statutory health insurance
schemes (n=117) were searched for second opinion programs and their features in
November 2016. All data was extracted by one person and verified by a second
person. RESULTS: In total, 78 second-opinion programs were identified. Half of
all statutory health insurance schemes (50%, n=59) provide at least one second
opinion program. The majority of them was in the field of orthopedics (78%, n=61)
and oncology (58%, n=45). Multiple replies were possible. In most cases, second
opinion programs were outsourced (58%; n=44), followed by forwarding patients to
health service providers contracted with the statutory health insurance scheme
(45% n=34). Only in 11% (n=8) was the second opinion delivered by staff of the
statutory health insurance scheme. The second opinion was delivered based on
submitted documents only (63%; n=48), direct patient-physician contact (43%;
n=33), and contact by phone (14%; n=11). The delivery of the second opinion took
7 days in median, while the delivery based on submitted documents only (median 7)
was faster than the delivery by direct-physician contact (median 14).
CONCLUSIONS: The majority of those living in Germany have the possibility to
obtain a second opinion. However, second-opinion programs are very heterogeneous
so that patients are confused about their rights to second opinion.
PMID- 28505705
TI - Crossed ectopic kidney: prenatal diagnosis and postnatal follow-up.
AB - OBJECTIVE: The objective of this study is to investigate prenatal diagnosis and
postnatal outcome of fetuses with crossed ectopic kidney. METHOD: Cases referred
for an empty renal fossa and diagnosed with crossed ectopic kidney confirmed
postnatally were analyzed retrospectively over a period of 10 years. Prenatal
diagnosis was established following the detection of one kidney in a normal
position and a second ipsilateral kidney fed by abnormal blood vessels on Doppler
flow RESULTS: Between 2005 and 2015, 185 fetuses were referred for an empty renal
fossa. Crossed ectopic kidney was diagnosed in 10 of them. Associated congenital
urological anomalies included two cases of double collecting system and bilateral
hydronephrosis in one. Associated extra renal findings were single umbilical
artery (4/10), ventricular septal defects (1/10), and persistent left superior
vena cava (1/10). On postnatal follow-up, bilateral vesicoureteral reflux was
diagnosed in a case who presented prenatally with bilateral hydronephrosis and
two cases of mild hydronephrosis. All cases were managed conservatively.
CONCLUSION: Crossed ectopic kidney should be suspected in cases presenting with
an empty renal fossa and a normal positioned kidney. Thorough anatomical scan
should be performed as well as periodic follow-up throughout pregnancy. Postnatal
nephrological follow-up is recommended. (c) 2017 John Wiley & Sons, Ltd.
PMID- 28505706
TI - The three-vessel and trachea view (3VTV) in the first trimester of pregnancy: an
additional tool in screening for congenital heart defects (CHD) in an unselected
population.
AB - OBJECTIVE: The aim of the study was to evaluate the feasibility of obtaining the
three-vessel and trachea view (3VTV) in an unselected population undergoing first
trimester screening for aneuploidy, and to investigate its role in the early
detection of congenital heart defects (CHD). METHODS: Cardiac examination was
performed by expert sonographers. Abnormal findings of 3VTV were classified in
three different subgroups: number, size and spatial relationship of the vessels.
RESULTS: We enrolled 6350 consecutive singleton pregnancies and included 5343
cases. Examination of 3VTV was feasible in 94% of cases. Fifty-seven (1%) CHD
were present in the study period; 24 cases were excluded because parents opted
for termination of pregnancy. Of the remaining 33 cases, 25 were suspected at the
first trimester and eight were detected only at the mid-trimester. An abnormal
3VTV was suspected in 22 cases, and it was confirmed in 21. Five cases that were
erroneously classified in the subgroup of abnormal vessel number were actually
characterized by a diminutive size of one of the great arteries. The detection
rate for CHD, including 4-CV and 3VTV, was 75.8%. CONCLUSIONS: Our study
demonstrates that 3VTV is an easy plane to obtain by expert sonographers in an
unselected population during first trimester. Typical suspicions include
detection of abnormal number, size or spatial relationship of the vessels. (c)
2017 John Wiley & Sons, Ltd.
PMID- 28505708
TI - Decomposition of strongly charged topological defects.
AB - We study decomposition of geometrically enforced nematic topological defects
bearing relatively large defect strengths m in effectively two-dimensional planar
systems. Theoretically, defect cores are analyzed within the mesoscopic Landau-de
Gennes approach in terms of the tensor nematic order parameter. We demonstrate a
robust tendency of defect decomposition into elementary units where two
qualitatively different scenarios imposing total defect strengths on a nematic
region are employed. Some theoretical predictions are verified experimentally,
where arrays of defects bearing charges m=+/-1 and even m=+/-2 are enforced
within a plane-parallel nematic cell using an atomic force microscopy scribing
method.
PMID- 28505707
TI - Numerical heating of electrons in particle-in-cell simulations of fully
magnetized plasmas.
AB - The role of spatial resolution of the electron gyroradius in electrostatic
particle-in-cell (PIC) simulations is studied. It is demonstrated that resolving
the gyroradius is crucial for simulations of strongly magnetized plasmas and that
nonresolving it results in substantial anisotropic heating of electrons. The
numerical heating can, in some cases, be suppressed by the higher-order weighting
to the grid, but it cannot be avoided. Possible mechanisms behind this numerical
heating are discussed. The study is carried out with a fully three dimensional
electrostatic PIC code with an external magnetic and electric fields.
PMID- 28505709
TI - Causal influence in linear Langevin networks without feedback.
AB - The intuition of causation is so fundamental that almost every research study in
life sciences refers to this concept. However, a widely accepted formal
definition of causal influence between observables is still missing. In the
framework of linear Langevin networks without feedback (linear response models)
we propose a measure of causal influence based on a new decomposition of
information flows over time. We discuss its main properties and we compare it
with other information measures like the transfer entropy. We are currently
unable to extend the definition of causal influence to systems with a general
feedback structure and nonlinearities.
PMID- 28505710
TI - Temperature of a single chaotic eigenstate.
AB - The onset of thermalization in a closed system of randomly interacting bosons at
the level of a single eigenstate is discussed. We focus on the emergence of Bose
Einstein distribution of single-particle occupation numbers, and we give a local
criterion for thermalization dependent on the eigenstate energy. We show how to
define the temperature of an eigenstate, provided that it has a chaotic structure
in the basis defined by the single-particle states. The analytical expression for
the eigenstate temperature as a function of both interparticle interaction and
energy is complemented by numerical data.
PMID- 28505711
TI - Critical behavior of hard squares in strong confinement.
AB - We examine the phase behavior of a quasi-one-dimensional system of hard squares
with side-length sigma, where the particles are confined between two parallel
walls and only nearest-neighbor interactions occur. As in our previous work
[Gurin, Varga, and Odriozola, Phys. Rev. E 94, 050603 (2016)]2470
004510.1103/PhysRevE.94.050603, the transfer operator method is used, but here we
impose a restricted orientation and position approximation to yield an analytic
description of the physical properties. This allows us to study the parallel
fluid-like to zigzag solid-like structural transition, where the compressibility
and heat capacity peaks sharpen and get higher as H->H_{c}=2sqrt[2]-1~1.8284 and
p->p_{c}=infinity. Here H is the width of the channel measured in sigma units and
p is the pressure. We have found that this structural change becomes critical at
the (p_{c},H_{c}) point. The obtained critical exponents belong to the
universality class of the one-dimensional Ising model. We believe this behavior
holds for the unrestricted orientational and positional case.
PMID- 28505712
TI - Sugar export limits size of conifer needles.
AB - Plant leaf size varies by more than three orders of magnitude, from a few
millimeters to over one meter. Conifer leaves, however, are relatively short and
the majority of needles are no longer than 6 cm. The reason for the strong
confinement of the trait-space is unknown. We show that sugars produced near the
tip of long needles cannot be exported efficiently, because the pressure required
to drive vascular flow would exceed the greatest available pressure (the osmotic
pressure). This basic constraint leads to the formation of an inactive region of
stagnant fluid near the needle tip, which does not contribute to sugar flow.
Remarkably, we find that the size of the active part does not scale with needle
length. We predict a single maximum needle size of 5 cm, in accord with data from
519 conifer species. This could help rationalize the recent observation that
conifers have significantly smaller leaves than angiosperms, and provide a
biophysical explanation for this intriguing difference between the two largest
groups of plants.
PMID- 28505713
TI - Molecular dynamics studies of electron-ion temperature equilibration in hydrogen
plasmas within the coupled-mode regime.
AB - We use classical molecular dynamics (MD) to study electron-ion temperature
equilibration in two-component plasmas in regimes for which the presence of
coupled collective modes has been predicted to substantively reduce the
equilibration rate. Guided by previous kinetic theory work, we examine hydrogen
plasmas at a density of n=10^{26}cm^{-3}, T_{i}=10^{5}K, and
10^{7}K and
that it is determined by p_{m}. In addition, we find that for SF networks the
minimum driver node densities needed to control the giant components of networks
decrease as the degree distribution exponents increase. Comparing the
controllability of the giant components of ER networks and SF networks, we find
that when the fraction of remaining nodes p is low, the giant in-connected, out
connected, and strong-connected components in ER networks have lower
controllability than those in SF networks.
PMID- 28505768
TI - Community detection, link prediction, and layer interdependence in multilayer
networks.
AB - Complex systems are often characterized by distinct types of interactions between
the same entities. These can be described as a multilayer network where each
layer represents one type of interaction. These layers may be interdependent in
complicated ways, revealing different kinds of structure in the network. In this
work we present a generative model, and an efficient expectation-maximization
algorithm, which allows us to perform inference tasks such as community detection
and link prediction in this setting. Our model assumes overlapping communities
that are common between the layers, while allowing these communities to affect
each layer in a different way, including arbitrary mixtures of assortative,
disassortative, or directed structure. It also gives us a mathematically
principled way to define the interdependence between layers, by measuring how
much information about one layer helps us predict links in another layer. In
particular, this allows us to bundle layers together to compress redundant
information and identify small groups of layers which suffice to predict the
remaining layers accurately. We illustrate these findings by analyzing synthetic
data and two real multilayer networks, one representing social support
relationships among villagers in South India and the other representing shared
genetic substring material between genes of the malaria parasite.
PMID- 28505770
TI - Resonance phonon approach to phonon relaxation time and mean free path in one
dimensional nonlinear lattices.
AB - We extend a previously proposed resonance phonon approach that is based on the
linear response theory. By studying the complex response function in depth, we
work out the phonon relaxation time besides the oscillating frequency of the
phonons in a few one-dimensional nonlinear lattices. The results in the large
wave-number-k regime agree with the expectations of the effective phonon theory.
However, in the small-k limit they follow different scaling laws. The phonon mean
free path can also be calculated indirectly. It coincides well with that derived
from the anharmonic phonon approach. A power-law divergent heat conduction, i.e.,
the heat conductivity kappa depends on lattice length N by kappa~N^{beta} with
beta>0, then is supported for the momentum-conserving lattices. Furthermore, this
approach can be applied to diatomic lattices. So obtained relaxation time
quantitatively agrees with that from the effective phonon theory. As for the mean
free path, the resonance phonon approach can detect both the acoustic and the
optical branches, whereas the anharmonic phonon approach can only detect a
combined branch, i.e., the acoustic branch for small k and the optical branch for
large k.
PMID- 28505771
TI - Counterexamples to Moffatt's statements on vortex knots.
AB - One of the well-known problems of hydrodynamics is studied: the problem of
classification of vortex knots for ideal fluid flows. In the literature there are
known Moffatt statements that all torus knots K_{m,n} for all rational numbers
m/n (0=4.
PMID- 28505776
TI - Thermal conductance of a two-level atom coupled to two quantum harmonic
oscillators.
AB - We have determined the thermal conductance of a system consisting of a two-level
atom coupled to two quantum harmonic oscillators in contact with heat reservoirs
at distinct temperatures. The calculation of the heat flux as well as the atomic
population and the rate of entropy production are obtained by the use of a
quantum Fokker-Planck-Kramers equation and by a Lindblad master equation. The
calculations are performed for small values of the coupling constant. The results
coming from both approaches show that the conductance is proportional to the
coupling constant squared and that, at high temperatures, it is proportional to
the inverse of temperature.
PMID- 28505777
TI - Impact of the dipole contribution on the terahertz emission of air-based plasma
induced by tightly focused femtosecond laser pulses.
AB - The present paper studies the generation mechanism of terahertz (THz) radiation
from tightly focused femtosecond laser pulses in a gas medium. We measured the
angular radiation pattern under different focusing conditions and observed that,
with the deepening of focus, the angular radiation pattern changes and optical-to
THz conversion efficiency increases. The analysis of the observed phenomena led
to the assumption that the dipole radiation prevails in most cases despite the
existing conception regarding the dominating role of the quadrupole mechanism of
radiation. Based on these assumptions, the transient photocurrent theory of the
phenomenon presented in this paper was developed by us and used for the numerical
fit of the experimental data.
PMID- 28505778
TI - Outcomes of the collapse of a large bubble in water at high ambient pressures.
AB - Presented here are observations of the outcomes of the collapses of large single
bubbles in H_{2}O and D_{2}O at high ambient pressures. Experiments were carried
out in a high-pressure spherical resonator at ambient pressures of up to 30 MPa
and acoustic pressures up to 35 MPa. Monitoring of the collapse events and their
outcomes was accomplished using multiframe high-speed photography. Among the
observations to be presented are the temporal and spatial evolution of light
emissions produced by the collapse events, which were observed to last on the
order of 30 ns and have time independent radii on the order of 30MUm; the
production of Rayleigh-Taylor jets which were observed to travel distances of up
to 70MUm at speeds in excess of 4500 m/s; the entrainment of the light emitting
regions in the jets' remnants; the production of spheroidal objects around the
collapse points of the bubbles, far from any surface of the resonator; and the
traversal and emergence of the Rayleigh-Taylor jets through the spherical
objects. These spheroidal objects appear to behave as amorphous solids and form
at locations where hydrodynamics predicts pressures in excess of the known
transition pressures of water into the high-pressure crystalline ices, Ice-VI and
Ice-VII.
PMID- 28505779
TI - Quantum entanglement and temperature fluctuations.
AB - In this paper, we consider entanglement in a system out of equilibrium, adopting
the viewpoint given by the formalism of superstatistics. Such an approach yields
a good effective description for a system in a slowly fluctuating environment
within a weak interaction between the system and the environment. For this
purpose, we introduce an alternative version of the formalism within a quantum
mechanical picture and use it to study entanglement in the Heisenberg XY model,
subject to temperature fluctuations. We consider both isotropic and anisotropic
cases and explore the effect of different temperature fluctuations (chi^{2}, log
normal, and F distributions). Our results suggest that particular fluctuations
may enhance entanglement and prevent it from vanishing at higher temperatures
than those predicted for the same system at thermal equilibrium.
PMID- 28505780
TI - How the site degree influences quantum probability on inhomogeneous substrates.
AB - We investigate the effect of the node degree and energy E on the electronic wave
function for regular and irregular structures, namely, regular lattices,
disordered percolation clusters, and complex networks. We evaluate the dependency
of the quantum probability for each site on its degree. For a class of biregular
structures formed by two disjoint subsets of sites sharing the same degree, the
probability P_{k}(E) of finding the electron on any site with k neighbors is
independent of E?0, a consequence of an exact analytical result that we prove for
any bipartite lattice. For more general nonbipartite structures, P_{k}(E) may
depend on E as illustrated by an exact evaluation of a one-dimensional
semiregular lattice: P_{k}(E) is large for small values of E when k is also
small, and its maximum values shift towards large values of |E| with increasing
k. Numerical evaluations of P_{k}(E) for two different types of percolation
clusters and the Apollonian network suggest that this observed feature might be
generally valid.
PMID- 28505781
TI - Statistical inference for community detection in signed networks.
AB - The problem of community detection in networks has received wide attention and
proves to be computationally challenging. In recent years, with the surge of
signed networks with positive links and negative links, to find community
structure in such signed networks has become a research focus in the area of
network science. Although many methods have been proposed to address the problem,
their performance seriously depends on the predefined optimization objectives or
heuristics which are usually difficult to accurately describe the intrinsic
structure of community. In this study, we present a statistical inference method
for community detection in signed networks, in which a probabilistic model is
proposed to model signed networks and the expectation-maximization-based
parameter estimation method is deduced to find communities in signed networks. In
addition, to efficiently analyze signed networks without any a priori
information, a model selection criterion is also proposed to automatically
determine the number of communities. In our experiments, the proposed method is
tested in the synthetic and real-word signed networks and compared with current
methods. The experimental results show the proposed method can more efficiently
and accurately find the communities in signed networks than current methods.
Notably, the proposed method is a mathematically principled method.
PMID- 28505782
TI - Nonequilibrium critical dynamics of the two-dimensional Ashkin-Teller model at
the Baxter line.
AB - We investigate the short-time universal behavior of the two-dimensional Ashkin
Teller model at the Baxter line by performing time-dependent Monte Carlo
simulations. First, as preparatory results, we obtain the critical parameters by
searching the optimal power-law decay of the magnetization. Thus, the dynamic
critical exponents theta_{m} and theta_{p}, related to the magnetic and electric
order parameters, as well as the persistence exponent theta_{g}, are estimated
using heat-bath Monte Carlo simulations. In addition, we estimate the dynamic
exponent z and the static critical exponents beta and nu for both order
parameters. We propose a refined method to estimate the static exponents that
considers two different averages: one that combines an internal average using
several seeds with another, which is taken over temporal variations in the power
laws. Moreover, we also performed the bootstrapping method for a complementary
analysis. Our results show that the ratio beta/nu exhibits universal behavior
along the critical line corroborating the conjecture for both magnetization and
polarization.
PMID- 28505783
TI - Low-frequency dielectric response of charged oblate spheroidal particles immersed
in an electrolyte.
AB - We study the low-frequency polarization response of a surface-charged oblate
spheroidal particle immersed in an electrolyte solution. Because the charged
spheroid attracts counterions which form the electric double layer around the
particle, using usual boundary conditions at the interface between the particle
and electrolyte can be quite complicated and challenging. Hence, we generalize
Fixman's boundary conditions, originally derived for spherical particles, to the
case of the charged oblate spheroid. Given two different counterion distributions
in the thin electric double-layer limit, we obtain analytic expressions for the
polarization coefficients to the first nontrivial order in frequency. We find
that the polarization response normal to the symmetry axis depends on the total
amount of charge carried by the oblate spheroid while that parallel to the
symmetry axis is suppressed when there is less charge on the edge of the
spheroid. We further study the overall dielectric response for a dilute
suspension of charged spheroids. We find that the dielectric enhancement at low
frequency, which is driven by the presence of a large zeta potential (surface
charge), is suppressed by high ion concentrations in the electrolyte and depends
on the size of the suspended particles. In addition, spheroids with higher aspect
ratios will also lead to a stronger dielectric enhancement due to the combination
of the electric double layer and textural effects. The characteristic frequency
associated with the dielectric enhancement scales inversely with the square of
the particle size, the major radius of the spheroid, and it has a weak dependence
on the shape of spheroids.
PMID- 28505784
TI - Spreading dynamics of forget-remember mechanism.
AB - We study extensively the forget-remember mechanism (FRM) for message spreading,
originally introduced in Eur. Phys. J. B 62, 247 (2008)EPJBFY1434
602810.1140/epjb/e2008-00139-4. The freedom of specifying forget-remember
functions governing the FRM can enrich the spreading dynamics to a very large
extent. The master equation is derived for describing the FRM dynamics. By
applying the mean field techniques, we have shown how the steady states can be
reached under certain conditions, which agrees well with the Monte Carlo
simulations. The distributions of forget and remember times can be explicitly
given when the forget-remember functions take linear or exponential forms, which
might shed some light on understanding the temporal nature of diseases like flu.
For time-dependent FRM there is an epidemic threshold related to the FRM
parameters. We have proven that the mean field critical transmissibility for the
SIS model and the critical transmissibility for the SIR model are the lower and
the the upper bounds of the critical transmissibility for the FRM model,
respectively.
PMID- 28505785
TI - Noise-induced polarization switching in complex networks.
AB - The combination of bistability and noise is ubiquitous in complex systems, from
biology to social interactions, and has important implications for their
functioning and resilience. Here we use a simple three-state dynamical process,
in which nodes go from one pole to another through an intermediate state, to show
that noise can induce polarization switching in bistable systems if dynamical
correlations are significant. In large, fully connected networks, where dynamical
correlations can be neglected, increasing noise yields a collapse of bistability
to an unpolarized configuration where the three possible states of the nodes are
equally likely. In contrast, increased noise induces abrupt and irreversible
polarization switching in sparsely connected networks. In multiplexes, where each
layer can have a different polarization tendency, one layer is dominant and
progressively imposes its polarization state on the other, offsetting or
promoting the ability of noise to switch its polarization. Overall, we show that
the interplay of noise and dynamical correlations can yield discontinuous
transitions between extremes, which cannot be explained by a simple mean-field
description.
PMID- 28505786
TI - Nonequilibrium nature of adaptation in bacterial chemotaxis: A fluctuation
dissipation theorem approach.
AB - Adaptation is a crucial biological function possessed by many sensory systems. In
this paper, we show that the fluctuation-dissipation theorem (FDT) serves as an
ideal mathematical tool to study adaptation. With the aid of the nonequilibrium
FDT developed by Seifert and Speck [Europhys. Lett. 89, 10007 (2010)EULEEJ0295
507510.1209/0295-5075/89/10007], we demonstrate the nonequilibrium nature of
adaptation in bacterial chemotaxis. We further show that nonequilibrium is a
necessary condition for adaptation even beyond the linear response regime using
the spectral theory of generator matrices. In particular, the results of this
paper are irrelevant to the specific functional forms of the model parameters.
This suggests that the nonequilibrium nature of adaptation is a topological
property, rather than a geometric property, of the underlying biochemical
reaction network.
PMID- 28505787
TI - Heat transport along a chain of coupled quantum harmonic oscillators.
AB - I study the heat transport properties of a chain of coupled quantum harmonic
oscillators in contact at its ends with two heat reservoirs at distinct
temperatures. My approach is based on the use of an evolution equation for the
density operator which is a canonical quantization of the classical Fokker-Planck
Kramers equation. I set up the evolution equation for the covariances and obtain
the stationary covariances at the stationary states from which I determine the
thermal conductance in closed form when the interparticle interaction is small.
The conductance is finite in the thermodynamic limit implying an infinite thermal
conductivity.
PMID- 28505789
TI - Manipulation and amplification of the Casimir force through surface fields using
helicity.
AB - We present both exact and numerical results for the behavior of the Casimir force
in O(n) systems with a finite extension L in one direction when the system is
subjected to surface fields that induce helicity in the order parameter. We show
that for such systems, the Casimir force in certain temperature ranges is of the
order of L^{-2}, both above and below the critical temperature, T_{c}, of the
bulk system. An example of such a system would be one with chemically modulated
bounding surfaces, in which the modulation couples directly to the system's order
parameter. We demonstrate that, depending on the parameters of the system, the
Casimir force can be either attractive or repulsive. The exact calculations
presented are for the one-dimensional XY and Heisenberg models under twisted
boundary conditions resulting from finite surface fields that differ in direction
by a specified angle, and the three-dimensional Gaussian model with surface
fields in the form of plane waves that are shifted in phase with respect to each
other. Additionally, we present exact and numerical results for the mean-field
version of the three-dimensional O(2) model with finite surface fields on the
bounding surfaces. We find that all significant results are consistent with the
expectations of finite-size scaling.
PMID- 28505788
TI - Flow and evolution of ice-sucrose crystal mushes.
AB - We study the rheology of suspensions of ice crystals at moderate to high volume
fractions in a sucrose solution in which they are partially soluble, a model
system for a wide class of crystal mushes or slurries. Under step changes in
shear rate, the viscosity changes to a relaxed value over several minutes, in a
manner well fitted by a single exponential. The behavior of the relaxed viscosity
is power-law shear thinning with shear rate, with an exponent of -1.76+/-0.25, so
that shear stress falls with increasing shear rate. On longer time scales, the
crystals ripen (leading to a falling viscosity) so that the mean radius increases
with time to the power 0.14+/-0.07. We speculate that this unusually small
exponent is due to the interaction of classical ripening dynamics with abrasion
or breakup under flow. We compare the rheological behavior to mechanistic models
based on flow-induced aggregation and breakup of crystal clusters, finding that
the exponents can be predicted from liquid phase sintering and breakup by brittle
fracture.
PMID- 28505790
TI - Multiparticle collision simulations of two-dimensional one-component plasmas:
Anomalous transport and dimensional crossovers.
AB - By means of hybrid multiparticle collsion-particle-in-cell (MPC-PIC) simulations
we study the dynamical scaling of energy and density correlations at equilibrium
in moderately coupled two-dimensional (2D) and quasi-one-dimensional (1D)
plasmas. We find that the predictions of nonlinear fluctuating hydrodynamics for
the structure factors of density and energy fluctuations in 1D systems with three
global conservation laws hold true also for 2D systems that are more extended
along one of the two spatial dimensions. Moreover, from the analysis of the
equilibrium energy correlators and density structure factors of both 1D and 2D
neutral plasmas, we find that neglecting the contribution of the fluctuations of
the vanishing self-consistent electrostatic fields overestimates the interval of
frequencies over which the anomalous transport is observed. Such violations of
the expected scaling in the currents correlation are found in different regimes,
hindering the observation of the asymptotic scaling predicted by the theory.
PMID- 28505791
TI - Driven flow with exclusion and spin-dependent transport in graphenelike
structures.
AB - We present a simplified description for spin-dependent electronic transport in
honeycomb-lattice structures with spin-orbit interactions, using generalizations
of the stochastic nonequilibrium model known as the totally asymmetric simple
exclusion process. Mean field theory and numerical simulations are used to study
currents, density profiles, and current polarization in quasi-one-dimensional
systems with open boundaries, and externally imposed particle injection (alpha)
and ejection (beta) rates. We investigate the influence of allowing for double
site occupancy, according to Pauli's exclusion principle, on the behavior of the
quantities of interest. We find that double occupancy shows strong signatures for
specific combinations of rates, namely high alpha and low beta, but otherwise its
effects are quantitatively suppressed. Comments are made on the possible
relevance of the present results to experiments on suitably doped graphenelike
structures.
PMID- 28505792
TI - Deffuant model on a ring with repelling mechanism and circular opinions.
AB - We investigate a Deffuant model on a ring by introducing two modifications: the
repelling mechanism and the circular opinions. The repelling mechanism drives the
opinions of two individuals away from each other and the circular opinions are
defined on a circle. We find that the repelling mechanism tends to polarize the
opinions of adjacent individuals and the circular opinions bring up a
spatiotemporal pattern in which all individuals take different opinions but the
opinion difference between two neighboring individuals tends to zero in the limit
of the population size. In the Deffuant model with both repelling mechanism and
the circular opinions, opinion dynamics depends on both the bounded confidence
and the convergence rate. The interplay between the repelling mechanism and the
circular opinion may give rise to time-dependent opinion dynamics.
PMID- 28505793
TI - Publisher's Note: Dynamics and thermodynamics of systems with long-range dipole
type interactions [Phys. Rev. E 95, 022110 (2017)].
AB - This corrects the article DOI: 10.1103/PhysRevE.95.022110.
PMID- 28505794
TI - How to desynchronize quorum-sensing networks.
AB - In this paper we investigate how so-called quorum-sensing networks can be
desynchronized. Such networks, which arise in many important application fields,
such as systems biology, are characterized by the fact that direct communication
between network nodes is superimposed to communication with a shared,
environmental variable. In particular, we provide a new sufficient condition
ensuring that the trajectories of these quorum-sensing networks diverge from
their synchronous evolution. Then, we apply our result to study two applications.
PMID- 28505795
TI - Parallelization of microfluidic flow-focusing devices.
AB - Microfluidic flow-focusing devices offer excellent control over fluid flow,
enabling formation of drops with a narrow size distribution. However, the
throughput of microfluidic flow-focusing devices is limited and scale-up through
operation of multiple drop makers in parallel often compromises the robustness of
their operation. We demonstrate that parallelization is facilitated if the outer
phase is injected from the direction opposite to that of the inner phase, because
the fluid injection flow rate, where the drop formation transitions from the
squeezing into the dripping regime, is shifted towards higher values.
PMID- 28505796
TI - Effects of a local defect on one-dimensional nonlinear surface growth.
AB - The slow-bond problem is a long-standing question about the minimal strength
epsilon_{c} of a local defect with global effects on the Kardar-Parisi-Zhang
(KPZ) universality class. A consensus on the issue has been delayed due to the
discrepancy between various analytical predictions claiming epsilon_{c}=0 and
numerical observations claiming epsilon_{c}>0. We revisit the problem via finite
size scaling analyses of the slow-bond effects, which are tested for different
boundary conditions through extensive Monte Carlo simulations. Our results
provide evidence that the previously reported nonzero epsilon_{c} is an artifact
of a crossover phenomenon which logarithmically converges to zero as the system
size goes to infinity.
PMID- 28505797
TI - Metastable memristive lines for signal transmission and information processing
applications.
AB - Traditional studies of memristive devices have mainly focused on their
applications in nonvolatile information storage and information processing. Here,
we demonstrate that the third fundamental component of information technologies
the transfer of information-can also be employed with memristive devices. For
this purpose, we introduce a metastable memristive circuit. Combining metastable
memristive circuits into a line, one obtains an architecture capable of
transferring a signal edge from one space location to another. We emphasize that
the suggested metastable memristive lines employ only resistive circuit
components. Moreover, their networks (for example, Y-connected lines) have an
information processing capability.
PMID- 28505798
TI - Modeling intra- and intermolecular correlations for linear and branched polymers
using a modified test-chain self-consistent field theory.
AB - A modified test-chain self-consistent field theory (SCFT) is presented to study
the intra- and intermolecular correlations of linear and branched polymers in
various solutions and melts. The key to the test-chain SCFT is to break the the
translational symmetry by fixing a monomer at the origin of a coordinate. This
theory successfully describes the crossover from self-avoiding walk at short
distances to screened random walk at long distances in a semidilute solution or
melt. The calculations indicated that branching enhances the swelling of polymers
in melts and influences stretching at short distances. The test-chain SCFT
calculations show good agreement with experiments and classic polymer theories.
We highlight that the theory presented here provides a solution to interpret the
polymer conformation and behavior under various conditions within the framework
of one theory.
PMID- 28505799
TI - Soliton excitations on a continuous-wave background in the modulational
instability regime with fourth-order effects.
AB - We study the correspondence between modulational instability and types of
fundamental nonlinear excitation in a nonlinear fiber with both third-order and
fourth-order effects. Some soliton excitations are obtained in the modulational
instability regime which have not been found in nonlinear fibers with second
order effects and third-order effects. Explicit analysis suggests that the
existence of solitons is related to the modulation stability circle in the
modulation instability regime, and they just exist in the modulational
instability regime outside of the modulational stability circle. It should be
emphasized that the solitons exist only with two special profiles on a continuous
wave background at a certain frequency. The evolution stability of the solitons
is tested numerically by adding some noise to initial states, which indicates
that they are robust against perturbations even in the modulation instability
regime. Further analysis indicates that solitons in the modulational instability
regime are caused by fourth-order effects.
PMID- 28505800
TI - Kramers problem for a dimer: Effect of noise correlations.
AB - The Kramers problem for a dimer in a bistable piecewise linear potential is
studied in the presence of correlated noise processes. The effect of such a
correlation is to redistribute the thermal power between the dynamical degrees of
freedom, and this leads to significant deviations in the dynamics of the system
from the case of independent noise processes. The distribution of first passage
times from one minima to the basin of attraction of the other minima is found to
have exponentially decaying tails with the parameter dependent on the amount of
correlation and the coupling between the particles. The strong coupling limit of
the problem is analyzed using adiabatic elimination, where it is found that the
initial probability density relaxes towards a stationary value on the same time
scale as the mean escape time when the noise intensity of the system is low. For
higher noise fluctuations, the relaxation towards the stationary state is slower
in comparison to escape times. In the extreme limit of perfect anticorrelation,
the random dynamical system behaves as a deterministic system in a steady state
in which the center of mass starting from the unstable maxima moves down the hill
and gets trapped in the potential minima. The implications for polymer dynamics
in a potential are discussed.
PMID- 28505801
TI - Finite-size scaling in the Kuramoto model.
AB - We investigate the scaling properties of the order parameter and the largest
nonvanishing Lyapunov exponent for the fully locked state in the Kuramoto model
with a finite number N of oscillators. We show that, for any finite value of N,
both quantities scale as (K-K_{L})^{1/2} with the coupling strength K
sufficiently close to the locking threshold K_{L}. We confirm numerically these
predictions for oscillator frequencies evenly spaced in the interval [-1,1] and
additionally find that the coupling range deltaK over which this scaling is valid
shrinks like deltaK~N^{-alpha} with alpha~1.5 as N->infinity. Away from this
interval, the order parameter exhibits the infinite-N behavior r-r_{L}~(K
K_{L})^{2/3} proposed by Pazo [Phys. Rev. E 72, 046211 (2005)]PLEEE81539
375510.1103/PhysRevE.72.046211. We argue that the crossover between the two
behaviors occurs because at the locking threshold, the upper bound of the
continuous part of the spectrum of the fully locked state approaches zero as N
increases. Our results clarify the convergence to the N->infinity limit in the
Kuramoto model.
PMID- 28505802
TI - Embryonic metabolism of the ornithischian dinosaurs Protoceratops andrewsi and
Hypacrosaurus stebingeri and implications for calculations of dinosaur egg
incubation times.
AB - The embryonic metabolisms of the ornithischian dinosaurs Protoceratops andrewsi
and Hypacrosaurus stebingeri have been determined and are in the range observed
in extant reptiles. The average value of the measured embryonic metabolic rates
for P. andrewsi and H. stebingeri are then used to calculate the incubation times
for 21 dinosaurs from both Sauischia and Ornithischia using a mass growth model
based on conservation of energy. The calculated incubation times vary from about
70 days for Archaeopteryx lithographica to about 180 days for Alamosaurus
sanjuanensis. Such long incubation times seem unlikely, particularly for the
sauropods and large theropods. Incubation times are also predicted with the
assumption that the saurischian dinosaurs had embryonic metabolisms in the range
observed in extant birds.
PMID- 28505803
TI - Simulating competitive egress of noncircular pedestrians.
AB - We present a numerical framework to simulate pedestrian dynamics in highly
competitive conditions by means of a force-based model implemented with
spherocylindrical particles instead of the traditional, symmetric disks. This
modification of the individuals' shape allows one to naturally reproduce recent
experimental findings of room evacuations through narrow doors in situations
where the contact pressure among the pedestrians was rather large. In particular,
we obtain a power-law tail distribution of the time lapses between the passage of
consecutive individuals. In addition, we show that this improvement leads to new
features where the particles' rotation acquires great significance.
PMID- 28505804
TI - Gauge-free cluster variational method by maximal messages and moment matching.
AB - We present an implementation of the cluster variational method (CVM) as a message
passing algorithm. The kind of message passing algorithm used for CVM, usually
named generalized belief propagation (GBP), is a generalization of the belief
propagation algorithm in the same way that CVM is a generalization of the Bethe
approximation for estimating the partition function. However, the connection
between fixed points of GBP and the extremal points of the CVM free energy is
usually not a one-to-one correspondence because of the existence of a gauge
transformation involving the GBP messages. Our contribution is twofold. First, we
propose a way of defining messages (fields) in a generic CVM approximation, such
that messages arrive on a given region from all its ancestors, and not only from
its direct parents, as in the standard parent-to-child GBP. We call this approach
maximal messages. Second, we focus on the case of binary variables,
reinterpreting the messages as fields enforcing the consistency between the
moments of the local (marginal) probability distributions. We provide a precise
rule to enforce all consistencies, avoiding any redundancy, that would otherwise
lead to a gauge transformation on the messages. This moment matching method is
gauge free, i.e., it guarantees that the resulting GBP is not gauge invariant. We
apply our maximal messages and moment matching GBP to obtain an analytical
expression for the critical temperature of the Ising model in general dimensions
at the level of plaquette CVM. The values obtained outperform Bethe estimates,
and are comparable with loop corrected belief propagation equations. The method
allows for a straightforward generalization to disordered systems.
PMID- 28505805
TI - Hysteresis in relative permeabilities suffices for propagation of saturation
overshoot: A quantitative comparison with experiment.
AB - Traditional Darcy theory for two-phase flow in porous media is shown to predict
the propagation of nonmonotone saturation profiles, also known as saturation
overshoot. The phenomenon depends sensitively on the constitutive parameters, on
initial conditions, and on boundary conditions. Hysteresis in relative
permeabilities is needed to observe the effect. Two hysteresis models are
discussed and compared. The shape of overshoot solutions can change as a function
of time or remain fixed and time independent. Traveling-wave-like overshoot
profiles of fixed width exist in experimentally accessible regions of parameter
space. They are compared quantitatively against experiment.
PMID- 28505806
TI - Kinetic discrimination of a polymerase in the presence of obstacles.
AB - One of the causes of high fidelity of copying in biological systems is kinetic
discrimination. In this mechanism larger dissipation and copying velocity result
in improved copying accuracy. We consider a model of a polymerase which
simultaneously copies a single-stranded RNA and opens a single- to double
stranded junction serving as an obstacle. The presence of the obstacle slows down
the motor, resulting in a change of its fidelity, which can be used to gain
information about the motor and junction dynamics. We find that the motor's
fidelity does not depend on details of the motor-junction interaction, such as
whether the interaction is passive or active. Analysis of the copying fidelity
can still be used as a tool for investigating the junction kinetics.
PMID- 28505807
TI - Effect of fractional blood flow on plasma skimming in the microvasculature.
AB - Although redistribution of red blood cells at bifurcated vessels is highly
dependent on flow rate, it is still challenging to quantitatively express the
dependence of flow rate in plasma skimming due to nonlinear cellular
interactions. We suggest a plasma skimming model that can involve the effect of
fractional blood flow at each bifurcation point. To validate the model, it is
compared with in vivo data at single bifurcation points, as well as microvascular
network systems. In the simulation results, the exponential decay of the plasma
skimming parameter M along fractional flow rate shows the best performance in
both cases.
PMID- 28505808
TI - Publisher's Note: Effect of the salt-induced micellar microstructure on the
nonlinear shear flow behavior of ionic cetylpyridinium chloride surfactant
solutions [Phys. Rev. E 95, 032603 (2017)].
AB - This corrects the article DOI: 10.1103/PhysRevE.95.032603.
PMID- 28505809
TI - Dissociation rates from single-molecule pulling experiments under large thermal
fluctuations or large applied force.
AB - Theories that are used to extract energy-landscape information from single
molecule pulling experiments in biophysics are all invariably based on Kramers'
theory of the thermally activated escape rate from a potential well. As is well
known, this theory recovers the Arrhenius dependence of the rate on the barrier
energy and crucially relies on the assumption that the barrier energy is much
larger than k_{B}T (limit of comparatively low thermal fluctuations). As was
shown already in Dudko et al. [Phys. Rev. Lett. 96, 108101 (2006)PRLTAO0031
900710.1103/PhysRevLett.96.108101], this approach leads to the unphysical
prediction of dissociation time increasing with decreasing binding energy when
the latter is lowered to values comparable to k_{B}T (limit of large thermal
fluctuations). We propose a theoretical framework (fully supported by numerical
simulations) which amends Kramers' theory in this limit and use it to extract the
dissociation rate from single-molecule experiments where now predictions are
physically meaningful and in agreement with simulations over the whole range of
applied forces (binding energies). These results are expected to be relevant for
a large number of experimental settings in single-molecule biophysics.
PMID- 28505810
TI - Effect of composition and pressure on the shear strength of sodium silicate
glasses: An atomic scale simulation study.
AB - The elastoplastic behavior of sodium silicate glasses is studied at different
scales as a function of composition and pressure, with the help of quasistatic
atomistic simulations. The samples are first compressed and then sheared at
constant pressure to calculate yield strength and permanent plastic deformations.
Changes occurring in the global response are then compared to the analysis of
local plastic rearrangements and strain heterogeneities. It is shown that the
plastic response results from the succession of well-identified localized
irreversible deformations occurring in a nanometer-size area. The size and the
number of these local rearrangements, as well as the amount of internal
deviatoric and volumetric plastic deformation, are sensitive to the composition
and to the pressure. In the early stages of the deformation, plastic
rearrangements are driven by sodium mobility. Consequently, the elastic yield
strength decreases when the sodium content increases, and the same when pressure
increases. Finally, good correlation was found between global and local stress
strain relationships, reinforcing again the role of sodium ions as local
initiators of the plastic behavior observed at larger scales.
PMID- 28505811
TI - Chaotic Lagrangian models for turbulent relative dispersion.
AB - A deterministic multiscale dynamical system is introduced and discussed as a
prototype model for relative dispersion in stationary, homogeneous, and isotropic
turbulence. Unlike stochastic diffusion models, here trajectory transport and
mixing properties are entirely controlled by Lagrangian chaos. The anomalous
"sweeping effect," a known drawback common to kinematic simulations, is removed
through the use of quasi-Lagrangian coordinates. Lagrangian dispersion statistics
of the model are accurately analyzed by computing the finite-scale Lyapunov
exponent (FSLE), which is the optimal measure of the scaling properties of
dispersion. FSLE scaling exponents provide a severe test to decide whether model
simulations are in agreement with theoretical expectations and/or observation.
The results of our numerical experiments cover a wide range of "Reynolds numbers"
and show that chaotic deterministic flows can be very efficient, and numerically
low-cost, models of turbulent trajectories in stationary, homogeneous, and
isotropic conditions. The mathematics of the model is relatively simple, and, in
a geophysical context, potential applications may regard small-scale
parametrization issues in general circulation models, mixed layer, and/or
boundary layer turbulence models as well as Lagrangian predictability studies.
PMID- 28505812
TI - Transient exchange fluctuation theorems for heat using a Hamiltonian framework:
Classical and quantum regimes.
AB - We investigate the statistics of heat exchange between a finite system coupled to
reservoir(s). We have obtained analytical results for heat fluctuation theorems
in the transient regime considering the Hamiltonian dynamics of the composite
system consisting of the system of interest and the heat bath(s). The system of
interest is driven by an external protocol. We first derive it in the context of
a single heat bath. The result is in exact agreement with known result. We then
generalize the treatment to two heat baths. We further extend the study to
quantum systems and show that relations similar to the classical case hold in the
quantum regime. For our study we invoke von Neumann two-point projective
measurement in quantum mechanics in the transient regime. The study of quantum
systems follows the same lines of argument as that of the classical system, and
as a result the treatment used in the latter complements that used in the former.
Our result is a generalization of Jarzynski-Wojcik heat fluctuation theorem.
PMID- 28505814
TI - Optimal detrended fluctuation analysis as a tool for the determination of the
roughness exponent of the mounded surfaces.
AB - We present an optimal detrended fluctuation analysis (DFA) and apply it to
evaluate the local roughness exponent in nonequilibrium surface growth models
with mounded morphology. Our method consists in analyzing the height fluctuations
computing the shortest distance of each point of the profile to a detrending
curve that fits the surface within the investigated interval. We compare the
optimal DFA (ODFA) with both the standard DFA and nondetrended analysis. We
validate the ODFA method considering a one-dimensional model in the Kardar-Parisi
Zhang universality class starting from a mounded initial condition. We applied
the methods to the Clarke-Vvedensky (CV) model in 2+1 dimensions with thermally
activated surface diffusion and absence of step barriers. It is expected that
this model belongs to the nonlinear molecular beam epitaxy (nMBE) universality
class. However, an explicit observation of the roughness exponent in agreement
with the nMBE class was still missing. The effective roughness exponent obtained
with ODFA agrees with the value expected for the nMBE class, whereas using the
other methods it does not agree. We also characterize the transient anomalous
scaling of the CV model and obtained that the corresponding exponent is in
agreement with the value reported for other nMBE models with weaker corrections
to the scaling.
PMID- 28505813
TI - Devil's staircase continuum in the chiral clock spin glass with competing
ferromagnetic-antiferromagnetic and left-right chiral interactions.
AB - The chiral clock spin-glass model with q=5 states, with both competing
ferromagnetic-antiferromagnetic and left-right chiral frustrations, is studied in
d=3 spatial dimensions by renormalization-group theory. The global phase diagram
is calculated in temperature, antiferromagnetic bond concentration p, random
chirality strength, and right-chirality concentration c. The system has a
ferromagnetic phase, a multitude of different chiral phases, a chiral spin-glass
phase, and a critical (algebraically) ordered phase. The ferromagnetic and chiral
phases accumulate at the disordered phase boundary and form a spectrum of devil's
staircases, where different ordered phases characteristically intercede at all
scales of phase-diagram space. Shallow and deep reentrances of the disordered
phase, bordered by fragments of regular and temperature-inverted devil's
staircases, are seen. The extremely rich phase diagrams are presented as
continuously and qualitatively changing videos.
PMID- 28505815
TI - Interaction of toroidal swimmers in Stokes flow.
AB - A doughnut-shaped object supporting surface rotations was a hypothetical
construct proposed by both Taylor and Purcell as a swimmer that would be able to
propel itself in a Stokesian fluid because of the irreversibility of its stroke.
Here we numerically examine the hydrodynamic interaction of pairs and trios of
these free toroidal swimmers. First, we study the axisymmetric case of two
toroidal swimmers placed in tandem, and show that a single torus of a corotating
pair is more efficient than when it swims alone, but less efficient when paired
with a counterrotating partner. Using a regularized Stokeslet framework, we study
the nonaxisymmetric case of toroidal swimmers whose axes are initially parallel,
but not collinear. These perturbed in tandem swimmers can exhibit qualitatively
different trajectories that may, for instance, repel the swimmers or have them
settle into a periodic state. We also illustrate interesting dynamics that occur
for different initial configurations of three tori.
PMID- 28505816
TI - Minimum energetic cost to maintain a target nonequilibrium state.
AB - In the absence of external driving, a system exposed to thermal fluctuations will
relax to equilibrium. However, the constant input of work makes it possible to
counteract this relaxation and maintain the system in a nonequilibrium steady
state. In this article, we use the stochastic thermodynamics of Markov jump
processes to compute the minimum rate at which energy must be supplied and
dissipated to maintain an arbitrary nonequilibrium distribution in a given energy
landscape. This lower bound depends on two factors: the undriven probability
current in the equilibrium state and the distance from thermal equilibrium of the
target distribution. By showing the consequences of this result in a few simple
examples, we suggest general implications for the required energetic costs of
macromolecular repair and cytosolic protein localization.
PMID- 28505817
TI - Fractal dimension and universality in avascular tumor growth.
AB - For years, the comprehension of the tumor growth process has been intriguing
scientists. New research has been constantly required to better understand the
complexity of this phenomenon. In this paper, we propose a mathematical model
that describes the properties, already known empirically, of avascular tumor
growth. We present, from an individual-level (microscopic) framework, an
explanation of some phenomenological (macroscopic) aspects of tumors, such as
their spatial form and the way they develop. Our approach is based on competitive
interaction between the cells. This simple rule makes the model able to reproduce
evidence observed in real tumors, such as exponential growth in their early stage
followed by power-law growth. The model also reproduces (i) the fractal-space
distribution of tumor cells and (ii) the universal growth behavior observed in
both animals and tumors. Our analyses suggest that the universal similarity
between tumor and animal growth comes from the fact that both can be described by
the same dynamic equation-the Bertalanffy-Richards model-even if they do not
necessarily share the same biological properties.
PMID- 28505818
TI - Anomalous temperature-dependent heat transport in one-dimensional momentum
conserving systems with soft-type interparticle interaction.
AB - We numerically investigate the heat transport problem in a one-dimensional
momentum-conserving lattice with a soft-type (ST) anharmonic interparticle
interaction. It is found that with the increase of the system's temperature,
while the introduction of ST anharmonicity softens phonons and decreases their
velocities, this type of nonlinearity like its hard type (HT) counterpart, can
still not be able to fully damp the longest wavelength phonons. Therefore, a
usual anomalous temperature dependence of heat transport with certain scaling
properties similarly to those shown in the Fermi-Pasta-Ulam-beta-like systems
with HT interactions can be seen. Our detailed examination from simulations
verifies this temperature-dependent behavior well.
PMID- 28505819
TI - Size dependence of static polymer droplet behavior from many-body dissipative
particle dynamics simulation.
AB - We used molecular simulation to study the static behavior of polymer droplets in
vacuum and on solid surfaces, namely the size of the droplet and the contact
angle, respectively. The effects of the polymer chain length and the total number
of particles were calculated by the many-body dissipative particle dynamics
method. For the spherical droplet containing the same number of particles, we
show that its radius depends on the polymer chain length. The radius of the
droplet is also proportional to one-third power of the total number of particles
for all given chain lengths. For the hemispherical droplet, the contact angle
increases with the number of particles in the droplet, and this effect is
relatively strong, especially for longer polymer chains. The effect of
wettability of the solid surface was also investigated by using polymerphobic
(low-affinity) and polymerphilic (high-affinity) surfaces. As the chain length
increases, the contact angle on the low-affinity surface decreases, while that on
the hydrophilic surface increases. The simulation reveals that there is a
critical affinity for the monomer on the solid surface; above and below which the
wettability increases and decreases as the molecular length increases,
respectively.
PMID- 28505820
TI - Robustness of free and pinned spiral waves against breakup by electrical forcing
in excitable chemical media.
AB - We present an investigation on the breakup of free and pinned spiral waves under
an applied electrical current in the Belousov-Zhabotinsky reaction. Spiral fronts
propagating towards the negative electrode are decelerated. A breakup of the
spiral waves occurs when some segments of the fronts are stopped by a
sufficiently strong electrical current. In the absence of obstacles (i.e., free
spiral waves), the critical value of the electrical current for the wave breakup
increases with the excitability of the medium. For spiral waves pinned to
circular obstacles, the critical electrical current increases with the obstacle
diameter. Analysis of spiral dynamics shows that the enhancement of the
robustness against the breakup of both free and pinned spiral waves is originated
by the increment of wave speed when either the excitability is strengthened or
the obstacle size is enlarged. The experimental findings are reproduced by
numerical simulations using the Oregonator model. In addition, the simulations
reveal that the robustness against the forced breakup increases with the
activator level in both cases of free and pinned spiral waves.
PMID- 28505821
TI - Stable swarming using adaptive long-range interactions.
AB - Sensory mechanisms in biology, from cells to humans, have the property of
adaptivity, whereby the response produced by the sensor is adapted to the overall
amplitude of the signal, reducing the sensitivity in the presence of strong
stimulus, while increasing it when it is weak. This property is inherently energy
consuming and a manifestation of the nonequilibrium nature of living organisms.
We explore here how adaptivity affects the effective forces that organisms feel
due to others in the context of a uniform swarm, in both two and three
dimensions. The interactions between the individuals are taken to be attractive
and long-range and of power-law form. We find that the effects of adaptivity
inside the swarm are dramatic, where the effective forces decrease (or remain
constant) with increasing swarm density. Linear stability analysis demonstrates
how this property prevents collapse (Jeans instability), when the forces are
adaptive. Adaptivity therefore endows swarms with a natural mechanism for self
stabilization.
PMID- 28505822
TI - Symmetry breaking by heating in a continuous opinion model.
AB - We study the critical behavior of a continuous opinion model, driven by kinetic
exchanges in a fully connected population. Opinions range in the real interval [
1,1], representing the different shades of opinions against and for an issue
under debate. Individuals' opinions evolve through pairwise interactions, with
couplings that are typically positive, but a fraction p of negative ones is
allowed. Moreover, a social temperature parameter T controls the tendency of the
individual responses toward neutrality. Depending on p and T, different
collective states emerge: symmetry broken (one side wins), symmetric (tie of
opposite sides), and absorbing neutral (indecision wins). We find the critical
points and exponents that characterize the phase transitions between them. The
symmetry breaking transition belongs to the usual Ising mean-field universality
class, but the absorbing-phase transitions, with beta=0.5, are out of the
paradigmatic directed percolation class. Moreover, ordered phases can emerge by
increasing social temperature.
PMID- 28505823
TI - Effect of internal mass in the lattice Boltzmann simulation of moving solid
bodies by the smoothed-profile method.
AB - A computational method for the simulation of particulate flows that can
efficiently treat the particle-fluid boundary in systems containing many
particles was developed based on the smoothed-profile lattice Boltzmann method
(SPLBM). In our proposed method, which we call the improved SPLBM (iSPLBM), for
an accurate and stable simulation of particulate flows, the hydrodynamic force on
a moving solid particle is exactly formulated with consideration of the effect of
internal fluid mass. To validate the accuracy and stability of iSPLBM, we
conducted numerical simulations of several particulate flow systems and compared
our results with those of other simulations and some experiments. In addition, we
performed simulations on flotation of many lightweight particles with a wide
range of particle size distribution, the results of which demonstrated the
effectiveness of iSPLBM. Our proposed model is a promising method to accurately
and stably simulate extensive particulate flows.
PMID- 28505824
TI - Classification framework for partially observed dynamical systems.
AB - We present a general framework for classifying partially observed dynamical
systems based on the idea of learning in the model space. In contrast to the
existing approaches using point estimates of model parameters to represent
individual data items, we employ posterior distributions over model parameters,
thus taking into account in a principled manner the uncertainty due to both the
generative (observational and/or dynamic noise) and observation (sampling in
time) processes. We evaluate the framework on two test beds: a biological pathway
model and a stochastic double-well system. Crucially, we show that the
classification performance is not impaired when the model structure used for
inferring posterior distributions is much more simple than the observation
generating model structure, provided the reduced-complexity inferential model
structure captures the essential characteristics needed for the given
classification task.
PMID- 28505825
TI - First-principles simulations of warm dense lithium fluoride.
AB - We perform first-principles path integral Monte Carlo (PIMC) and density
functional theory molecular dynamics (DFT-MD) calculations to explore warm dense
matter states of LiF. Our simulations cover a wide density-temperature range of
2.08-15.70gcm^{-3} and 10^{4}-10^{9} K. Since PIMC and DFT-MD accurately treat
effects of atomic shell structure, we find a pronounced compression maximum and a
shoulder on the principal Hugoniot curve attributed to K-shell and L-shell
ionization. The results provide a benchmark for widely used EOS tables, such as
SESAME, LEOS, and models. In addition, we compute pair-correlation functions that
reveal an evolving plasma structure and ionization process that is driven by
thermal and pressure ionization. Finally, we compute electronic density of states
of liquid LiF from DFT-MD simulations and find that the electronic gap can remain
open with increasing density and temperature to at least 15.7 gcm^{-3}.
PMID- 28505826
TI - Steepest-entropy-ascent nonequilibrium quantum thermodynamic framework to model
chemical reaction rates at an atomistic level.
AB - The steepest entropy ascent (SEA) dynamical principle provides a general
framework for modeling the dynamics of nonequilibrium (NE) phenomena at any level
of description, including the atomistic one. It has recently been shown to
provide a precise implementation and meaning to the maximum entropy production
principle and to encompass many well-established theories of nonequilibrium
thermodynamics into a single unifying geometrical framework. Its original
formulation in the framework of quantum thermodynamics (QT) assumes the simplest
and most natural Fisher-Rao metric to geometrize from a dynamical standpoint the
manifold of density operators, which represent the thermodynamic NE states of the
system. This simplest SEAQT formulation is used here to develop a general
mathematical framework for modeling the NE time evolution of the quantum state of
a chemically reactive mixture at an atomistic level. The method is illustrated
for a simple two-reaction kinetic scheme of the overall reaction F+H_{2}<=>HF+F
in an isolated tank of fixed volume. However, the general formalism is developed
for a reactive system subject to multiple reaction mechanisms. To explicitly
implement the SEAQT nonlinear law of evolution for the density operator, both the
energy and the particle number eigenvalue problems are set up and solved
analytically under the dilute gas approximation. The system-level energy and
particle number eigenvalues and eigenstates are used in the SEAQT equation of
motion to determine the time evolution of the density operator, thus effectively
describing the overall kinetics of the reacting system as it relaxes toward
stable chemical equilibrium. The predicted time evolution in the near-equilibrium
limit is compared to the reaction rates given by a standard detailed kinetic
model so as to extract the single time constant needed by the present SEA model.
PMID- 28505827
TI - Intermittent feedback induces attractor selection.
AB - We present a method for attractor selection in multistable dynamical systems. It
involves a feedback term that is active only when the dynamics of the system is
in a particular fraction of state space of the attractor. We implement this
method first on a simplest symmetric chaotic flow and then on a bistable neuronal
system. We find that adding this space-dependent feedback term to the dynamical
equations of these systems will drive the dynamics to the desired attractor by
annihilating the other. We further demonstrate that the attractor selection due
to this feedback term can be used in construction of logic gates, which is one of
the practical applications of the proposed method.
PMID- 28505828
TI - Applications of the first digit law to measure correlations.
AB - The quasiempirical Benford law predicts that the distribution of the first
significant digit of random numbers obtained from mixed probability distributions
is surprisingly meaningful and reveals some universal behavior. We generalize
this finding to examine the joint first-digit probability of a pair of two random
numbers and show that undetectable correlations by means of the usual covariance
based measure can be identified in the statistics of the corresponding first
digits. We illustrate this new measure by analyzing the correlations and
anticorrelations of the positions of two interacting particles in their quantum
mechanical ground state. This suggests that by using this measure, the presence
or absence of correlations can be determined even if only the first digit of
noisy experimental data can be measured accurately.
PMID- 28505829
TI - Control of amplitude chimeras by time delay in oscillator networks.
AB - We investigate the influence of time-delayed coupling in a ring network of
nonlocally coupled Stuart-Landau oscillators upon chimera states, i.e., space
time patterns with coexisting partially coherent and partially incoherent
domains. We focus on amplitude chimeras, which exhibit incoherent behavior with
respect to the amplitude rather than the phase and are transient patterns, and we
show that their lifetime can be significantly enhanced by coupling delay. To
characterize their transition to phase-lag synchronization (coherent traveling
waves) and other coherent structures, we generalize the Kuramoto order parameter.
Contrasting the results for instantaneous coupling with those for constant
coupling delay, for time-varying delay, and for distributed-delay coupling, we
demonstrate that the lifetime of amplitude chimera states and related partially
incoherent states can be controlled, i.e., deliberately reduced or increased,
depending upon the type of coupling delay.
PMID- 28505830
TI - Modeling and statistical analysis of non-Gaussian random fields with heavy-tailed
distributions.
AB - In this paper, we investigate and develop an alternative approach to the
numerical analysis and characterization of random fluctuations with the heavy
tailed probability distribution function (PDF), such as turbulent heat flow and
solar flare fluctuations. We identify the heavy-tailed random fluctuations based
on the scaling properties of the tail exponent of the PDF, power-law growth of
qth order correlation function, and the self-similar properties of the contour
lines in two-dimensional random fields. Moreover, this work leads to a
substitution for the fractional Edwards-Wilkinson (EW) equation that works in the
presence of MU-stable Levy noise. Our proposed model explains the configuration
dynamics of the systems with heavy-tailed correlated random fluctuations. We also
present an alternative solution to the fractional EW equation in the presence of
MU-stable Levy noise in the steady state, which is implemented numerically, using
the MU-stable fractional Levy motion. Based on the analysis of the self-similar
properties of contour loops, we numerically show that the scaling properties of
contour loop ensembles can qualitatively and quantitatively distinguish non
Gaussian random fields from Gaussian random fluctuations.
PMID- 28505831
TI - Fast-switching chiral nematic liquid-crystal mode with polymer-sustained twisted
vertical alignment.
AB - We demonstrate a fast-switching liquid-crystal mode with polymer-sustained
twisted vertical alignment. By optimizing the polymerization condition, a polymer
microstructure with controlled orientation is produced. The polymer
microstructure not only synergistically suppresses the optical bounce during
field-induced homeotropic-twist transition but also shortens the response time
significantly. Theoretical analyses validate that the ground state free energy
density is modified by the aligning field of the polymer microstructure, which
affects the driving voltage of the device. The outcomes of this paper will enable
the development of fast-switching and achromatic electro-optical and photonic
devices.
PMID- 28505832
TI - Analysis of force treatment in the pseudopotential lattice Boltzmann equation
method.
AB - In this paper, different force treatments are analyzed in detail for a
pseudopotential lattice Boltzmann equation (LBE), and the contribution of third
order error terms to pressure tensor with a force scheme is analyzed by a higher
order Chapman-Enskog expansion technique. From the theoretical analysis, the
performance of the original force treatment of Shan-Chen (SC), Ladd, Guo et al.,
and the exact difference method (EDM) are E_{Ladd}=1, while E_{Ladd}180 we find a steady formation of a centered
hexagonal lattice that smoothly transforms to valence circular rings in the
ground-state configurations for both potentials.
PMID- 28505837
TI - Electrophoresis of a polarizable charged colloid with hydrophobic surface: A
numerical study.
AB - We consider the electrophoresis of a charged colloid for a generalized situation
in which the particle is considered to be polarizable and the surface exhibits
hydrophobicity. The dielectric polarization of the particle creates a nonlinear
dependence of the electrophoretic velocity on the applied electric field, and the
core hydrophobicity amplifies the fluid convection in the Debye layer. Thus, a
linear analysis is no longer applicable for this situation. The present analysis
is based on the numerical solution of the nonlinear electrokinetic equations
based on the Navier-Stokes-Nernst-Planck-Poisson equations coupled with the
Laplace equation for the electric field within the dielectric particle. The
hydrophobicity of the particle may influence its electric polarization by
enhancing the convective transport of ions. The nonlinear effects, such as double
layer polarization and relaxation, are also influenced by the hydrophobicity of
the particle surface. The present results compare well for a lower range of the
applied electric field and surface charge density with the existing results for a
perfectly dielectric particle with a hydrophobic surface based on the first-order
perturbation analysis due to Khair and Squires [Phys. Fluids 21, 042001
(2009)PHFLE61070-663110.1063/1.3116664]. Dielectric polarization creates a
reduction in particle electrophoretic velocity, and its impact is strong for a
moderate range of Debye length. A quantitative measure of the nonlinear effects
is demonstrated by comparing the electrophoretic velocity with an existing linear
model.
PMID- 28505836
TI - Stationary patterns in star networks of bistable units: Theory and application to
chemical reactions.
AB - We present theoretical and experimental studies on pattern formation with
bistable dynamical units coupled in a star network configuration. By applying a
localized perturbation to the central or the peripheral elements, we demonstrate
the subsequent spreading, pinning, or retraction of the activations; such
analysis enables the characterization of the formation of stationary patterns of
localized activity. The results are interpreted with a theoretical analysis of a
simplified bistable reaction-diffusion model. Weak coupling results in trivial
pinned states where the activation cannot propagate. At strong coupling, a
uniform state is expected with active or inactive elements at small or large
degree networks, respectively. A nontrivial stationary spatial pattern,
corresponding to an activation pinning, is predicted to occur at an intermediate
number of peripheral elements and at intermediate coupling strengths, where the
central activation of the network is pinned, but the peripheral activation
propagates toward the center. The results are confirmed in experiments with star
networks of bistable electrochemical reactions. The experiments confirm the
existence of the stationary spatial patterns and the dependence of coupling
strength on the number of peripheral elements for transitions between pinned and
retreating or spreading fronts in forced network configurations (where the
central or periphery elements are forced to maintain their states).
PMID- 28505838
TI - Correlations induced by depressing synapses in critically self-organized networks
with quenched dynamics.
AB - In a recent work, mean-field analysis and computer simulations were employed to
analyze critical self-organization in networks of excitable cellular automata
where randomly chosen synapses in the network were depressed after each spike
(the so-called annealed dynamics). Calculations agree with simulations of the
annealed version, showing that the nominal branching ratio sigma converges to
unity in the thermodynamic limit, as expected of a self-organized critical
system. However, the question remains whether the same results apply to the
biological case where only the synapses of firing neurons are depressed (the so
called quenched dynamics). We show that simulations of the quenched model yield
significant deviations from sigma=1 due to spatial correlations. However, the
model is shown to be critical, as the largest eigenvalue of the synaptic matrix
approaches unity in the thermodynamic limit, that is, lambda_{c}=1. We also study
the finite size effects near the critical state as a function of the parameters
of the synaptic dynamics.
PMID- 28505839
TI - Explosive percolation on a scale-free multifractal weighted planar stochastic
lattice.
AB - In this article, we investigate explosive bond percolation (EBP) with the product
rule, formally known as the Achlioptas process, on a scale-free multifractal
weighted planar stochastic lattice. One of the key features of the EBP transition
is the delay, compared to the corresponding random bond percolation (RBP), in the
onset of the spanning cluster. However, when it happens, it happens so
dramatically that initially it was believed, although ultimately proved wrong,
that explosive percolation (EP) exhibits a first-order transition. In the case of
EP, much effort has been devoted to resolving the issue of its order of
transition and almost no effort has been devoted to finding the critical point,
critical exponents, etc., to classify it into universality classes. This is in
sharp contrast to the situation for classical random percolation. We do not even
know all the exponents of EP for a regular planar lattice or for an Erdos-Renyi
network. We first find the critical point p_{c} numerically and then obtain all
the critical exponents, beta, gamma, and nu, as well as the Fisher exponent tau
and the fractal dimension d_{f} of the spanning cluster. We also compare our
results for EBP with those for RBP and find that all the exponents of EBP obey
the same scaling relations as do those for RBP. Our findings suggest that EBP is
not special except for the fact that the exponent beta is unusually small
compared to that for RBP.
PMID- 28505840
TI - Evolutionary fields can explain patterns of high-dimensional complexity in
ecology.
AB - One of the properties that make ecological systems so unique is the range of
complex behavioral patterns that can be exhibited by even the simplest
communities with only a few species. Much of this complexity is commonly
attributed to stochastic factors that have very high-degrees of freedom. Orthodox
study of the evolution of these simple networks has generally been limited in its
ability to explain complexity, since it restricts evolutionary adaptation to an
inertia-free process with few degrees of freedom in which only gradual,
moderately complex behaviors are possible. We propose a model inspired by
particle-mediated field phenomena in classical physics in combination with
fundamental concepts in adaptation, which suggests that small but high
dimensional chaotic dynamics near to the adaptive trait optimum could help
explain complex properties shared by most ecological datasets, such as
aperiodicity and pink, fractal noise spectra. By examining a simple predator-prey
model and appealing to real ecological data, we show that this type of complexity
could be easily confused for or confounded by stochasticity, especially when
spurred on or amplified by stochastic factors that share variational and spectral
properties with the underlying dynamics.
PMID- 28505841
TI - Optimal strengthening of particle-loaded liquid foams.
AB - Foams made of complex fluids such as particle suspensions have a great potential
for the development of advanced aerated materials. In this paper, we study the
rheological behavior of liquid foams loaded with granular suspensions. We focus
on the effect of small particles, i.e., particle-to-bubble size ratio smaller
than 0.1, and we measure the complex modulus as a function of particle size and
particle volume fraction. With respect to previous work, the results highlight a
new elastic regime characterized by unequaled modulus values as well as
independence of size ratio. A careful investigation of the material
microstructure reveals that particles organize through the network between the
gas bubbles and form a granular skeleton structure with tightly packed particles.
The latter is proven to be responsible for the reported new elastic regime.
Rheological probing performed by strain sweep reveals a two-step yielding of the
material: The first one occurs at small strain and is clearly attributed to
yielding of the granular skeleton; the second one corresponds to the yielding of
the bubble assembly, as observed for particle-free foams. Moreover, the elastic
modulus measured at small strain is quantitatively described by models for solid
foams in assuming that the granular skeleton possesses a bulk elastic modulus of
order 100 kPa. Additional rheology experiments performed on the bulk granular
material indicate that this surprisingly high value can be understood as soon as
the magnitude of the confinement pressure exerted by foam bubbles on packed
grains is considered.
PMID- 28505842
TI - Spontaneous symmetry breaking due to the trade-off between attractive and
repulsive couplings.
AB - Spontaneous symmetry breaking is an important phenomenon observed in various
fields including physics and biology. In this connection, we here show that the
trade-off between attractive and repulsive couplings can induce spontaneous
symmetry breaking in a homogeneous system of coupled oscillators. With a simple
model of a system of two coupled Stuart-Landau oscillators, we demonstrate how
the tendency of attractive coupling in inducing in-phase synchronized (IPS)
oscillations and the tendency of repulsive coupling in inducing out-of-phase
synchronized oscillations compete with each other and give rise to symmetry
breaking oscillatory states and interesting multistabilities. Further, we provide
explicit expressions for synchronized and antisynchronized oscillatory states as
well as the so called oscillation death (OD) state and study their stability. If
the Hopf bifurcation parameter (lambda) is greater than the natural frequency
(omega) of the system, the attractive coupling favors the emergence of an
antisymmetric OD state via a Hopf bifurcation whereas the repulsive coupling
favors the emergence of a similar state through a saddle-node bifurcation. We
show that an increase in the repulsive coupling not only destabilizes the IPS
state but also facilitates the reentrance of the IPS state.
PMID- 28505843
TI - Quantum resonant activation.
AB - Quantum resonant activation is investigated for the archetype setup of an
externally driven two-state (spin-boson) system subjected to strong dissipation
by means of both analytical and extensive numerical calculations. The phenomenon
of resonant activation emerges in the presence of either randomly fluctuating or
deterministic periodically varying driving fields. Addressing the incoherent
regime, a characteristic minimum emerges in the mean first passage time to reach
an absorbing neighboring state whenever the intrinsic time scale of the
modulation matches the characteristic time scale of the system dynamics. For the
case of deterministic periodic driving, the first passage time probability
density function (pdf) displays a complex, multipeaked behavior, which depends
crucially on the details of initial phase, frequency, and strength of the
driving. As an interesting feature we find that the mean first passage time
enters the resonant activation regime at a critical frequency nu^{*} which
depends very weakly on the strength of the driving. Moreover, we provide the
relation between the first passage time pdf and the statistics of residence
times.
PMID- 28505844
TI - Equation of state, phonons, and lattice stability of ultrafast warm dense matter.
AB - Using the two-temperature model for ultrafast matter (UFM), we compare the
equation of state, pair-distribution functions g(r), and phonons using the
neutral pseudoatom (NPA) model with results from density functional theory (DFT)
codes and molecular dynamics (MD) simulations for Al, Li, and Na. The NPA
approach uses state-dependent first-principles pseudopotentials from an "all
electron" DFT calculation with finite-T exchange-correlation functional (XCF). It
provides pair potentials, structure factors, the "bound" and "free" states, as
well as a mean ionization Z[over -] unambiguously. These are not easily
accessible via DFT+MD calculations which become prohibitive for T/T_{F} exceeding
~0.6, where T_{F} is the Fermi temperature. Hence, both DFT+MD and NPA methods
can be compared up to ~8eV, while higher T can be addressed via the NPA. The high
T_{e} phonon calculations raise the question of UFM lattice stability and surface
ablation in thin UFM samples. The ablation forces in a UFM slab are used to
define an "ablation time" competing with phonon formation times in thin UFM
samples. Excellent agreement for all properties is found between NPA and standard
DFT codes, even for Li where a strongly nonlocal pseudopotential is used in DFT
codes. The need to use pseudopotentials appropriate to the ionization state
Z[over -] is emphasized. The effect of finite-T XCF is illustrated via its effect
on the pressure and the electron-density distribution at a nucleus.
PMID- 28505845
TI - Thermodynamics of complexity and pattern manipulation.
AB - Many organisms capitalize on their ability to predict the environment to maximize
available free energy and reinvest this energy to create new complex structures.
This functionality relies on the manipulation of patterns-temporally ordered
sequences of data. Here, we propose a framework to describe pattern manipulators
devices that convert thermodynamic work to patterns or vice versa-and use them to
build a "pattern engine" that facilitates a thermodynamic cycle of pattern
creation and consumption. We show that the least heat dissipation is achieved by
the provably simplest devices, the ones that exhibit desired operational behavior
while maintaining the least internal memory. We derive the ultimate limits of
this heat dissipation and show that it is generally nonzero and connected with
the pattern's intrinsic crypticity-a complexity theoretic quantity that captures
the puzzling difference between the amount of information the pattern's past
behavior reveals about its future and the amount one needs to communicate about
this past to optimally predict the future.
PMID- 28505846
TI - Traveling waves and worms in ac-driven electroconvection under external
multiplicative noise.
AB - In the presence of external multiplicative noise, ac-driven electroconvection
(EC) in a nematic liquid crystal is investigated. Noise-induced traveling waves
(TWs) including localized ones (worms) are found with a typical, stationary wave.
Three kinds of TWs are classified by their dynamic features (e.g., noise
intensity-dependent Hopf frequency and space-time map). Moreover, ac frequency
dependent threshold voltages of EC are examined in high noise intensities causing
abnormal charge redistribution of the EC cell, and the roles of ac and noise
fields with respect to TWs are elucidated in successive pattern evolutions. The
mechanism of TWs is discussed in terms of a locally perturbed dynamic
conductivity due to the noise field additionally applied to the EC; such a
conductivity can be related to a weak-electrolyte model for a Hopf bifurcation to
a TW.
PMID- 28505847
TI - Numerical analysis of the lattice Boltzmann method for simulation of linear
acoustic waves.
AB - We analyze a linear lattice Boltzmann (LB) formulation for simulation of linear
acoustic wave propagation in heterogeneous media. We employ the single-relaxation
time Bhatnagar-Gross-Krook as well as the general multirelaxation-time collision
operators. By calculating the dispersion relation for various 2D lattices, we
show that the D2Q5 lattice is the most suitable model for the linear acoustic
problem. We also implement a grid-refinement algorithm for the LB scheme to
simulate waves propagating in a heterogeneous medium with velocity contrasts. Our
results show that the LB scheme performance is comparable to the classical second
order finite-difference schemes. Given its efficiency for parallel computation,
the LB method can be a cost effective tool for the simulation of linear acoustic
waves in complex geometries and multiphase media.
PMID- 28505848
TI - Emergent community agglomeration from data set geometry.
AB - In the statistical learning language, samples are snapshots of random vectors
drawn from some unknown distribution. Such vectors usually reside in a high
dimensional Euclidean space, and thus the "curse of dimensionality" often
undermines the power of learning methods, including community detection and
clustering algorithms, that rely on Euclidean geometry. This paper presents the
idea of effective dissimilarity transformation (EDT) on empirical dissimilarity
hyperspheres and studies its effects using synthetic and gene expression data
sets. Iterating the EDT turns a static data distribution into a dynamical process
purely driven by the empirical data set geometry and adaptively ameliorates the
curse of dimensionality, partly through changing the topology of a Euclidean
feature space R^{n} into a compact hypersphere S^{n}. The EDT often improves the
performance of hierarchical clustering via the automatic grouping information
emerging from global interactions of data points. The EDT is not restricted to
hierarchical clustering, and other learning methods based on pairwise
dissimilarity should also benefit from the many desirable properties of EDT.
PMID- 28505849
TI - Compaction of noncohesive and cohesive granular materials under vibrations:
Experiments and stochastic model.
AB - We study the time evolution of the compaction of a noncohesive or cohesive
granular material submitted to shaking through experiments and a stochastic
model. Beyond well-known empirical expressions, we show that the characteristic
time scales depend on the number of objects in the assembly. For a noncohesive
granular material, the compaction time scale is governed by the number of
individual grains in the system. In the case of a cohesive granular material, a
two-scale model (individual particles and clusters) allows one to mimic the time
evolution of the compaction of an actual cohesive powder driven by horizontal
vibrations. In this case, the two time scales are associated with the numbers of
clusters and grains, respectively.
PMID- 28505850
TI - Damage cluster distributions in numerical concrete at the mesoscale.
AB - We investigate the size distribution of damage clusters in concrete under
uniaxial tension loading conditions. Using the finite-element method, the
concrete is modeled at the mesoscale by a random distribution of elastic
spherical aggregates within an elastic mortar paste. The propagation and
coalescence of damage zones are then simulated by means of dynamically inserted
cohesive elements. Dynamic failure analysis shows that the size distribution of
damage clusters follows a power law when a system-spanning cluster is first
observed, with an exponent close to that of percolation theory. This is found for
a range of selected mesostructural parameters, material defects, and applied
strain rates. In all cases, the system-spanning cluster occurs prior to the onset
of local decohesion, a regime of crack nucleation and propagation, and eventual
material failure. The resulting fully damaged crack surfaces after failure are
found to be only weakly correlated with the percolated damage region structures.
PMID- 28505851
TI - Rogue waves in nonlocal media.
AB - The generation of rogue waves is investigated in a class of nonlocal nonlinear
Schrodinger (NLS) equations. In this system, modulation instability is suppressed
as the effect of nonlocality increases. Despite this fact, there is a parameter
regime where the number and amplitude of the rogue events increase as compared to
the standard NLS equation, which is a limit of the system when nonlocality
vanishes. Furthermore, the nature of these waves is investigated; while no
analytical solutions are known to model these events, it is shown, numerically,
that these rogue events differ significantly from the rational soliton
(Peregrine) solution of the limiting NLS equation. The universal structure of the
associated rogue waves is discussed and a local description is presented. These
results can help in the experimental realization of rogue waves in these media.
PMID- 28505852
TI - Generation of higher-order rogue waves from multibreathers by double degeneracy
in an optical fiber.
AB - In this paper, we construct a special kind of breather solution of the nonlinear
Schrodinger (NLS) equation, the so-called breather-positon (b-positon for short),
which can be obtained by taking the limit lambda_{j}->lambda_{1} of the Lax pair
eigenvalues in the order-n periodic solution, which is generated by the n-fold
Darboux transformation from a special "seed" solution-plane wave. Further, an
order-n b-positon gives an order-n rogue wave under a limit lambda_{1}
>lambda_{0}. Here, lambda_{0} is a special eigenvalue in a breather of the NLS
equation such that its period goes to infinity. Several analytical plots of order
2 breather confirm visually this double degeneration. The last limit in this
double degeneration can be realized approximately in an optical fiber governed by
the NLS equation, in which an injected initial ideal pulse is created by a
frequency comb system and a programable optical filter (wave shaper) according to
the profile of an analytical form of the b-positon at a certain position z_{0}.
We also suggest a new way to observe higher-order rogue waves generation in an
optical fiber, namely, measure the patterns at the central region of the higher
order b-positon generated by above ideal initial pulses when lambda_{1} is very
close to the lambda_{0}. The excellent agreement between the numerical solutions
generated from initial ideal inputs with a low signal-to-noise ratio and
analytical solutions of order-2 b-positon supports strongly this way in a
realistic optical fiber system. Our results also show the validity of the
generating mechanism of a higher-order rogue waves from a multibreathers through
the double degeneration.
PMID- 28505853
TI - Dynamic stabilization of Janus sphere trans-dimers.
AB - We experimentally investigated the self-assembly of chemically active colloidal
Janus spheres into dimers. The trans-dimer conformation, in which the two active
sites are oriented roughly in opposite directions and the particles are osculated
at their equators, becomes dominant as the hydrogen peroxide fuel concentration
increases. Our observations suggest high spinning frequency combined with little
translational motion is at least partially responsible for the stabilization of
the trans-dimer as activity increases.
PMID- 28505854
TI - Mean-field equations for neuronal networks with arbitrary degree distributions.
AB - The emergent dynamics in networks of recurrently coupled spiking neurons depends
on the interplay between single-cell dynamics and network topology. Most
theoretical studies on network dynamics have assumed simple topologies, such as
connections that are made randomly and independently with a fixed probability
(Erdos-Renyi network) (ER) or all-to-all connected networks. However, recent
findings from slice experiments suggest that the actual patterns of connectivity
between cortical neurons are more structured than in the ER random network. Here
we explore how introducing additional higher-order statistical structure into the
connectivity can affect the dynamics in neuronal networks. Specifically, we
consider networks in which the number of presynaptic and postsynaptic contacts
for each neuron, the degrees, are drawn from a joint degree distribution. We
derive mean-field equations for a single population of homogeneous neurons and
for a network of excitatory and inhibitory neurons, where the neurons can have
arbitrary degree distributions. Through analysis of the mean-field equations and
simulation of networks of integrate-and-fire neurons, we show that such networks
have potentially much richer dynamics than an equivalent ER network. Finally, we
relate the degree distributions to so-called cortical motifs.
PMID- 28505855
TI - Theoretical models for magneto-sensitive elastomers: A comparison between
continuum and dipole approaches.
AB - In the literature, different theoretical models have been proposed to describe
the properties of systems which consist of magnetizable particles that are
embedded into an elastomer matrix. It is well known that such magneto-sensitive
elastomers display a strong magneto-mechanical coupling when subjected to an
external magnetic field. Nevertheless, the predictions of available models often
vary significantly since they are based on different assumptions and
approximations. Up to now the actual accuracy and the limits of applicability are
widely unknown. In the present work, we compare the results of a microscale
continuum and a dipolar mean field approach with regard to their predictions for
the magnetostrictive response of magneto-sensitive elastomers and reveal some
fundamental relations between the relevant quantities in both theories. It turns
out that there is a very good agreement between both modeling strategies,
especially for entirely random microstructures. In contrast, a comparison of the
finite-element results with a modified approach, which-similar to the continuum
model-is based on calculations with discrete particle distributions, reveals
clear deviations. Our systematic analysis of the differences shows to what extent
the dipolar mean field approach is superior to other dipole models.
PMID- 28505856
TI - Information thermodynamics for feedback processes with the appearance of
overshooting.
AB - We investigate feedback processes with measurement-induced protocols for
particular tasks that drive systems in specified directions in state spaces. We
focus on mutual information as a measure of correlation between system and
memory, which has been known to play a crucial role for the second law of
information thermodynamics. The performance of task is enhanced in the early
stage of driving, along with the decrease of correlation and mutual information
due to the passage from initial measurement. However, we find that the
performance is suppressed if the time of driving exceeds a threshold, which we
call feedback overshooting. We find that a type of correlation, anticorrelation,
between system and memory is built up as a result of overshooting and gives rise
to regaining mutual information. We examine the effect of overshooting in detail
from two examples. We study the Szilard engine for the task of work extraction.
We also study a recurrent feedback with finite time interval for the task to
reduce the mean square distance of a colloid below the value by thermal
fluctuation. We find that recurrent feedback is stable only for a moderate range
of time intervals and the intensity of feedback protocol. We discuss the problem
of divergence of mutual information for error-free measurement.
PMID- 28505857
TI - Ising spin glasses in two dimensions: Universality and nonuniversality.
AB - Following numerous earlier studies, extensive simulations and analyses were made
on the continuous interaction distribution Gaussian model and the discrete
bimodal interaction distribution Ising spin glass (ISG) models in two dimensions
[Lundow and Campbell, Phys. Rev. E 93, 022119 (2016)1539
375510.1103/PhysRevE.93.022119]. Here we further analyze the bimodal and Gaussian
data together with data on two other continuous interaction distribution two
dimensional ISG models, the uniform and the Laplacian models, and three other
discrete interaction distribution models, a diluted bimodal model, an
"antidiluted" model, and a more exotic symmetric Poisson model. Comparisons
between the three continuous distribution models show that not only do they share
the same exponent eta=0 but that to within the present numerical precision they
share the same critical exponent nu also, and so lie in a single universality
class. On the other hand the critical exponents of the four discrete distribution
models are not the same as those of the continuous distributions, and the present
data strongly indicate that they differ from one discrete distribution model to
another. This is evidence that discrete distribution ISG models in two dimensions
have nonzero values of the critical exponent eta and do not lie in a single
universality class.
PMID- 28505858
TI - Tricritical behavior of nonequilibrium Ising spins in fluctuating environments.
AB - We investigate the phase transitions in a coupled system of Ising spins and a
fluctuating network. Each spin interacts with q neighbors through links of the
rewiring network. The Ising spins and the network are in thermal contact with the
heat baths at temperatures T_{S} and T_{L}, respectively, so the whole system is
driven out of equilibrium for T_{S}?T_{L}. The model is a generalization of the q
neighbor Ising model [A. Jedrzejewski et al., Phys. Rev. E 92, 052105
(2015)PLEEE81539-375510.1103/PhysRevE.92.052105], which corresponds to the
limiting case of T_{L}=infinity. Despite the mean-field nature of the
interaction, the q-neighbor Ising model was shown to display a discontinuous
phase transition for q>=4. Setting up the rate equations for the magnetization
and the energy density, we obtain the phase diagram in the T_{S}-T_{L} parameter
space. The phase diagram consists of a ferromagnetic phase and a paramagnetic
phase. The two phases are separated by a continuous phase transition belonging to
the mean-field universality class or by a discontinuous phase transition with an
intervening coexistence phase. The equilibrium system with T_{S}=T_{L} falls into
the former case while the q-neighbor Ising model falls into the latter case. At
the tricritical point, the system exhibits the mean-field tricritical behavior.
Our model demonstrates a possibility that a continuous phase transition turns
into a discontinuous transition by a nonequilibrium driving. Heat flow induced by
the temperature difference between two heat baths is also studied.
PMID- 28505859
TI - Interpolation between low and high temperatures of the specific heat for spin
systems.
AB - The high temperature expansion (HTE) of the specific heat of a spin system fails
at low temperatures, even if it is combined with a Pade approximation. On the
other hand, we often have information about the low-temperature asymptotics (LTA)
of the system. Interpolation methods combine both kind of information, HTE and
LTA, in order to obtain an approximation of the specific heat that holds for the
whole temperature range. Here we revisit the entropy method that has been
previously published and propose two variants that better cope with problems of
the entropy method for gapped systems. We compare all three methods applied to
the antiferromagnetic Haldane spin-one chain and especially apply the second
variant, called log Z method, to the cuboctahedron for different spin quantum
numbers. In particular, we demonstrate that the interpolation method is able to
detect an extra low-temperature maximum in the specific heat that may appear if a
separation of two energy scales is present in the considered system. Finally, we
illustrate how interpolation also works for classical spin systems.
PMID- 28505860
TI - Nonmonotonic DNA-length-dependent mobility in pluronic gels.
AB - Two-dimensional electrophoresis was used to analyze the mobility of DNA fragments
in micellar gels of pluronic F127 (EO_{100}PO_{70}EO_{100}) and pluronic P123
(EO_{20}PO_{70}EO_{20}). The 20-3500 base pair DNA fragments were separated by
size first in agarose gels, and then in pluronic gels at room temperature. In
agarose gels, the DNA mobility decreases monotonically with increasing DNA
length. In pluronic gels, however, the mobility varies nonmonotonically according
to fragment lengths that are strongly correlated with the diameter of the
spherical micelles. Brownian dynamics (BD) simulations with short-ranged intra
DNA hydrodynamic interactions were performed to numerically calculate the length
dependent mobility in pluronic lattices. The rising and falling trends, as well
as the oscillations of mobility, were captured by the coarse-grained BD
simulations. Molecular dynamics simulations in pluronic F127, with explicitly
modeled micelle coronas, justified that the hydrodynamic interactions mediated by
the complex fluid of hydrated poly(ethylene oxide) are a possible reason for the
initial rise of mobility with DNA length.
PMID- 28505861
TI - Landau-Zener tunneling of solitons.
AB - We consider Landau-Zener tunneling of solitons in a weakly coupled two-channel
system, for this purpose we construct a simple mechanical system using two weakly
coupled chains of nonlinear oscillators with gradually decreasing (first chain)
and increasing (second chain) masses. The model allows us to consider soliton
propagation and Landau-Zener tunneling between the chains. It is shown that
soliton tunneling characteristics become drastically dependent on its amplitude
in nonlinear regime. The validity of the developed tunneling theory is justified
via comparison with direct numerical simulations on oscillator ladder system.
PMID- 28505862
TI - Thermodynamic state variables in quasiequilibrium ultracold neutral plasma.
AB - The pressure and internal energy of an ultracold plasma in a state of
quasiequilibrium are evaluated using classical molecular dynamics simulations.
Coulomb collapse is avoided by modeling electron-ion interactions using an
attractive Coulomb potential with a repulsive core. We present a method to
separate the contribution of classical bound states, which form due to
recombination, from the contribution of free charges when evaluating these
thermodynamic state variables. It is found that the contribution from free
charges is independent of the choice of repulsive core length scale when it is
sufficiently short-ranged. The partial pressure associated with the free charges
is found to closely follow that of the one-component plasma model, reaching
negative values at strong coupling, while the total system pressure remains
positive. This pseudopotential model is also applied to Debye-Huckel theory to
describe the weakly coupled regime.
PMID- 28505863
TI - Mixing and the fractal geometry of piecewise isometries.
AB - Mathematical concepts often have applicability in areas that may have surprised
their original developers. This is the case with piecewise isometries (PWIs),
which transform an object by cutting it into pieces that are then rearranged to
reconstruct the original object, and which also provide a paradigm to study
mixing via cutting and shuffling in physical sciences and engineering. Every PWI
is characterized by a geometric structure called the exceptional set, E, whose
complement comprises nonmixing regions in the domain. Varying the parameters that
define the PWI changes both the structure of E as well as the degree of mixing
the PWI produces, which begs the question of how to determine which parameters
produce the best mixing. Motivated by mixing of yield stress materials, for
example granular media, in physical systems, we use numerical simulations of PWIs
on a hemispherical shell and examine how the fat fractal properties of E relate
to the degree of mixing for any particular PWI. We present numerical evidence
that the fractional coverage of E negatively correlates with the intensity of
segregation, a standard measure for the degree of mixing, which suggests that
fundamental properties of E such as fractional coverage can be used to predict
the effectiveness of a particular PWI as a mixing mechanism.
PMID- 28505864
TI - Optimal subgrid scheme for shell models of turbulence.
AB - We discuss a theoretical framework to define an optimal subgrid closure for shell
models of turbulence. The closure is based on the ansatz that consecutive shell
multipliers are short-range correlated, following the third hypothesis of
Kolmogorov formulated for similar quantities for the original three-dimensional
Navier-Stokes turbulence. We also propose a series of systematic approximations
to the optimal model by assuming different degrees of correlations across scales
among amplitudes and phases of consecutive multipliers. We show numerically that
such low-order closures work well, reproducing all known properties of the large
scale dynamics including anomalous scaling. We found small but systematic
discrepancies only for a range of scales close to the subgrid threshold, which do
not tend to disappear by increasing the order of the approximation. We speculate
that the lack of convergence might be due to a structural instability, at least
for the evolution of very fast degrees of freedom at small scales. Connections
with similar problems for large eddy simulations of the three-dimensional Navier
Stokes equations are also discussed.
PMID- 28505865
TI - Critical behavior of the two-dimensional nonequilibrium zero-temperature random
field Ising model on a triangular lattice.
AB - We present a numerical study of the critical behavior of the nonequilibrium zero
temperature random field Ising model in two dimensions on a triangular lattice.
Our findings, based on the scaling analysis and collapse of data collected in
extensive simulations of systems with linear sizes up to L=65536, show that the
model is in a different universality class than the same model on a quadratic
lattice, which is relevant for a better understanding of model universality and
the analysis of experimental data.
PMID- 28505866
TI - Spatial uniformity in the power-grid system.
AB - Robust synchronization is indispensable for stable operation of a power grid.
Recently, it has been reported that a large number of decentralized generators,
rather than a small number of large power plants, provide enhanced
synchronization together with greater robustness against structural failures. In
this paper, we systematically control the spatial uniformity of the geographical
distribution of generators and conclude that the more uniformly generators are
distributed, the more enhanced synchronization occurs. In the presence of
temporal failures of power sources, we observe that spatial uniformity helps the
power grid to recover stationarity in a shorter time. We also discuss practical
implications of our results in designing the structure of a power-grid network.
PMID- 28505867
TI - Collective dynamics out of thermodynamic equilibrium.
AB - Thorough numerical studies reveal that spatially extended dissipative systems
with long-range interactions may give rise to a large-scale dynamics. This
phenomenon, which generalizes mean-field chaos, can be interpreted as a form of
subtle pattern formation, where a chaotic microscopic dynamics coexists with a
macroscopic irregular behavior, sustained by the spontaneous emergence of long
wavelength "hydrodynamic" modes. This regime can emerge only if the coupling is
sufficiently long ranged, otherwise normal space-time chaos is observed. In
Stuart-Landau oscillators a further regime is found, where the amplitude of the
hydrodynamic modes exhibits an anomalous intermediate scaling between that of
collective and standard space-time chaos.
PMID- 28505868
TI - Limiting similarity of competitive species and demographic stochasticity.
AB - The limiting similarity of competitive species and its relationship with the
competitive exclusion principle is still one of the most important concepts in
ecology. In the 1970s, May [R. M. May, Stability and Complexity in Model
Ecosystems (Princeton University, Princeton, NJ, 1973)] developed a concise
theoretical framework to investigate the limiting similarity of competitive
species. His theoretical results show that no limiting similarity threshold of
competitive species can be identified in the deterministic model system whereby
species more similar than this threshold never coexist. Theoretically, for
competitive species coexisting in an unvarying environment, deterministic
interspecific interactions and demographic stochasticity can be considered two
sides of a coin. To investigate how the "tension" between these two forces
affects the coexistence of competing species, a simple two-species competitive
system based only on May's model system is transformed into an equivalent
replicator equation. The effect of demographic stochasticity on the system
stability is measured by the expected drift of the Lyapunov function. Our main
results show that the limiting similarity of competitive species should not be
considered to be an absolute measure. Specifically, very similar competitive
species should be able to coexist in an environment with a high productivity
level but big differences between competitive species should be necessary in an
ecosystem with a low productivity level.
PMID- 28505869
TI - Instability onset and scaling laws of an auto-oscillating turbulent flow in a
complex plasma.
AB - We study a complex plasma under microgravity conditions that is first stabilized
with an oscillating electric field. Once the stabilization is stopped, the so
called heartbeat instability develops. We study how the kinetic energy spectrum
changes during and after the onset of the instability and compare with the double
cascade predicted by Kraichnan and Leith for two-dimensional turbulence. The
onset of the instability manifests clearly in the ratio of the reduced rates of
cascade of energy and enstrophy and in the power-law exponents of the energy
spectra.
PMID- 28505871
TI - Phase behavior of the thermotropic melt of asymmetric V-shaped molecules.
AB - The phase behavior of the monodisperse melt of V-shaped molecules composed of two
rigid segments of different lengths joined at their ends at an external angle
alpha has been examined within the Landau-de Gennes approach. Each rigid segment
consists of a sequence of monomer units; the anisotropic interactions in the
system are assumed to be of the Maier-Saupe form. The coefficients of the Landau
de Gennes free-energy expansion have been found from a microscopic model of V
shaped molecule. A single Landau point at which the system undergoes direct
continuous transition from isotropic to biaxial nematic phase is found for
asymmetry parameter phi=1/3 or phi=2/3, where phi is the number fraction of
monomer units in one of the segments. Two Landau points are found in a range
1/3~t^{1/2} for t->+infinity. The results, presented here, shed light
on the origin of subdiffusion in systems with a broad distribution of relaxation
times.
PMID- 28505879
TI - Nitrogen utilization and environmental losses in organic greenhouse lettuce
amended with two distinct biochars.
AB - The potential of biochar to prevent nitrogen (N) losses and improve plant
performance were studied across various levels of N input for two growing seasons
in mesocosms simulating an organic lettuce production system. A silt loam soil
was amended with pine chip (PC) and walnut shell (WS) biochar (10tha-1) in
combination with five organic N fertilization rates (0, 56, 112, 168, and
225kgNha-1). The N output through harvest, leachate, and N2O emissions were
measured to assess N utilization and environmental losses of biochar-amended
soils. For both biochars, only at the 100% N fertilization rate was lettuce
biomass production improved with significant increases in N use efficiency (NUE);
however, only PC biochar decreased N losses via leaching (at 100% N fertilization
rate) and seasonal N2O emissions (at 50% N fertilization rate). Thus, due to
increases in plant biomass and decreases in N losses, PC biochar significantly
decreased the ratio of N lost over N exported in biomass. Findings from this
study suggest that both WS and PC biochars can improve organic lettuce production
but only at 225kgNha-1. Decreases in N losses via leachate and N2O emissions vary
with fertilization level and biochar type.
PMID- 28505878
TI - Suspended solid concentration reduces feeding in freshwater mussels.
AB - We examined the effect of TSS concentration on the clearance rates (CR) of newly
transformed juvenile and adult Lampsilis fasciola, L. siliquoidea, Ligumia
nasuta, and Villosa iris, as increased total suspended solids (TSS) are thought
to interfere with feeding processes. Mussel CR were measured in aerated (or
swirled for juveniles) chambers at TSS concentrations up to 15mgL-1 for
laboratory-transformed juveniles, and up to 100mgL-1 for adult mussels. The CR of
one-week old animals increased with TSS concentration, likely due to ontological
differences in feeding (pedal vs. suspension feeding) and gill development, but
CR decreased monotonically with TSS concentration in older animals (two-, three-
and four-week old juveniles). The CR of adult mussels were significantly lower at
TSS concentrations >=8mgL-1, which represented a threshold in CR. Although this
threshold occurred at similar concentrations across the four species, the decline
in CR was largest in L. fasciola (46% compared to no-TSS control), and smallest
in V. iris (21%). Differences among species are likely related to differences in
the TSS and substrate found in their source rivers given that greater decline
occurred for species in rivers with relatively lower TSS. The decrease in CR as
TSS increased is consistent across marine and freshwater bivalves, at both
juvenile and adult stages. The decrease in feeding was five times greater in
juvenile compared to adult bivalves, which indicates how the vulnerability to
environmental stressors differ across life stages. These results demonstrate that
TSS reduces suspension feeding rates in freshwater unionids, therefore TSS should
be managed to ensure their survival.
PMID- 28505881
TI - Herbaceous or Salix miyabeana 'SX64' narrow buffer strips as a means to minimize
glyphosate and aminomethylphosphonic acid leaching from row crop fields.
AB - Glyphosate is the most widely used herbicide worldwide and is now frequently
detected in surface waters of agricultural regions, notably in Quebec (Canada).
Numerous legislations require vegetated riparian buffer strips (RBS) along
agricultural streams. Quebec policy requires 3-meter-wide RBS. The present study
evaluates the efficiency of narrow herbaceous and low- or high-density (33,333
and 55,556stumps/ha) willow, Salix miyabeana 'SX64', RBS, to minimize leaching of
glyphosate and its main degradation product (AMPA) from agricultural fields to
streams. Our study compared triplicate treatments of herbaceous and willow
planted RBS located in an organic-rich soil at Boisbriand (BB) and in a mineral
soil at Saint-Roch-de-l'Achigan (SR). Runoff water was sampled with surface
collectors and interstitial water was collected with 35cm or 70cm tension
lysimeters. Potential efficiency of the RBS is reported as the percent reduction
between edge-of-field and edge-of-stream concentrations in runoff and
interstitial waters. Neither glyphosate nor AMPA in runoff were significantly
intercepted by the RBS. After field herbicide spraying, glyphosate measured in SR
surface soils (0-20cm) was on average 210MUg.kg-1 dw (range from undetected to
<=317MUg.kg-1 dw). Glyphosate was found to be persistent and its infiltration
towards groundwater may be enhanced by the RBS. Contrary to runoff trends, soil
glyphosate was significantly less concentrated on the SR edge-of-stream compared
to edge-of-field (27-54% potential efficiency). The potential efficiency of
herbaceous, low- and high-density willow RBS were undifferentiated.
PMID- 28505882
TI - Stemflow-induced spatial heterogeneity of radiocesium concentrations and stocks
in the soil of a broadleaved deciduous forest.
AB - The transport of radiocesium from the canopy and quantification of the spatial
distribution of radiocesium in the soil of konara oak forests are important to
better understand the variability of 137Cs stocks in the soil between proximal
and distal stem areas as well as fine-scale variations around the tree trunk.
Moreover, a better understanding of fine-scale spatial variabilities of 137Cs
concentrations and stocks will provide insights for optimizing soil sampling
strategies to provide a more robust estimation of contamination at the stand
scale. This study aims to elucidate the transport of 137Cs by stemflow in a
radioactively contaminated konara oak forest in Tsukuba, Japan by describing and
quantifying the fine-scale spatial distribution of 137Cs in the soil and
preferential flowpaths of stemflow on the tree stem by a dye tracing experiment.
137Cs concentrations and stocks were higher in the soils of the proximal stem
area than distal stem area when they corresponded with the preferential flowpaths
of stemflow. There was a significant relationship between canopy projection area
of individual trees and average soil 137Cs concentrations and stocks, even though
canopies of the trees overlapped. Our results demonstrate that the spatiality of
137Cs concentrations and stocks in the soil of the proximal stem area are
governed (at least partially) by the preferential flowpaths of stemflow along the
tree trunk. In addition, higher 137Cs concentrations and stocks in the near-trunk
soils of trees with larger crown areas might be caused by an enhanced ability to
capture dry deposition.
PMID- 28505883
TI - Spatial patterns and temporal trends of trace metal mass budgets in the western
Adriatic sediments (Mediterranean Sea).
AB - Spatial patterns of major (Al, Fe and Ti) and trace metals (Cu, Cr, Mn, Ni, Pb
and Zn) measured in surficial sediments collected within the Late-Holocene mud
wedge in the western Adriatic Sea were analyzed to elucidate their sources,
transport and mass budgets. Distributions of sedimentary trace metals, their
fluvial inputs and accumulation loads reveal along-shore transport towards the
southern Adriatic. Pb and to a lower extent Zn accumulation loads over time
decreased significantly since 1988 in the North Adriatic, consistently with the
implementation of regulations in the Western Europe, whereas Zn accumulation in
the Po River prodelta remained unchanged since 1995. The Po River fluvial inputs
accounted for half of Cr, Ni, Pb and Zn of the fluvial inputs into the western
Adriatic Sea, contributing for the delivery of important amounts of Cr and Ni
into the sediments, probably related to the natural occurrence of ultramafic
rocks in the North sector. Collectively, ~30% of trace metal fluvial inputs
discharged into the North sector are exported to the Central and South sectors.
The Po River acts as both a bypass and an accumulation zone. In contrast, trace
metal accumulation in the Central sector far exceed trace metal fluvial inputs,
which suggested that this area is a preferential sink for particle-reactive river
borne material from the North Adriatic. The North sector shows moderate
enrichment of Zn and Pb mainly related to the Po River influence. The
anthropogenic fraction of Pb shows a large drop of ~30% from the North sector
southwards, whereas Zn proportions remain fairly the same up to the Central
sector only decreasing in the South sector.
PMID- 28505880
TI - Redox regulation of ischemic limb neovascularization - What we have learned from
animal studies.
AB - Mouse hindlimb ischemia has been widely used as a model to study peripheral
artery disease. Genetic modulation of the enzymatic source of oxidants or
components of the antioxidant system reveal that physiological levels of oxidants
are essential to promote the process of arteriogenesis and angiogenesis after
femoral artery occlusion, although mice with diabetes or atherosclerosis may have
higher deleterious levels of oxidants. Therefore, fine control of oxidants is
required to stimulate vascularization in the limb muscle. Oxidants transduce
cellular signaling through oxidative modifications of redox sensitive cysteine
thiols. Of particular importance, the reversible modification with abundant
glutathione, called S-glutathionylation (or GSH adducts), is relatively stable
and alters protein function including signaling, transcription, and cytoskeletal
arrangement. Glutaredoxin-1 (Glrx) is an enzyme which catalyzes reversal of GSH
adducts, and does not scavenge oxidants itself. Glrx may control redox signaling
under fluctuation of oxidants levels. In ischemic muscle increased GSH adducts
through Glrx deletion improves in vivo limb revascularization, indicating
endogenous Glrx has anti-angiogenic roles. In accordance, Glrx overexpression
attenuates VEGF signaling in vitro and ischemic vascularization in vivo. There
are several Glrx targets including HIF-1alpha which may contribute to inhibition
of vascularization by reducing GSH adducts. These animal studies provide a
caution that excess antioxidants may be counter-productive for treatment of
ischemic limbs, and highlights Glrx as a potential therapeutic target to improve
ischemic limb vascularization.
PMID- 28505884
TI - Experimental studies on combustion of composite biomass pellets in fluidized bed.
AB - This work presents studies on the combustion of Composite Biomass Pellets (CBPS)
in fluidized bed using bauxite particles as the bed material. Prior to the
combustion experiment, cold-flow characterization and thermogravimetric analysis
are performed to investigate the effect of air velocity and combustion mechanism
of CBPS. The cold-state test shows that CBPs and bauxite particles fluidize well
in the fluidized bed. However, because of the presence of large CBPs,
optimization of the fluidization velocity is rather challenging. CBPs can gather
at the bottom of the fluidized bed at lower gas velocities. On the contrary, when
the velocity is too high, they accumulate in the upper section of the fluidized
bed. The suitable fluidization velocity for the system in this study was found to
be between 1.5-2.0m/s. At the same time, it is found that the critical
fluidization velocity and the pressure fluctuation of the two-component system
increase with the increase of CBPs mass concentration. The thermogravimetric
experiment verifies that the combustion of CBPs is a first-order reaction, and it
is divided into three stages: (i) dehydration, (ii) release and combustion of the
volatile and (iii) the coke combustion. The combustion of CBPs is mainly based on
the stage of volatile combustion, and its activation energy is greater than that
of char combustion. During the combustion test, CBPS are burned at a 10kg/h feed
rate, while the excess air is varied from 25% to 100%. Temperatures of the bed
and flue gas concentrations (O2, CO, SO2 and NO) are recorded. CBPs can be burnt
stably, and the temperature of dense phase is maintained at 765-780 degrees C.
With the increase of the air velocity, the main combustion region has a tendency
to move up. While the combustion is stable, O2 and CO2 concentrations are
maintained at about 7%, and 12%, respectively. The concentration of SO2 in the
flue gas after the initial stage of combustion is nearly zero. Furthermore, NO
concentration is found to be closely related to O2: the NO reaches its peak value
after initial stage and later decreases with the continued depletion of O2.
Towards the end of combustion, NO increases with the increase of O2.
PMID- 28505885
TI - Occurrence and environmental impact of pharmaceutical residues from conventional
and natural wastewater treatment plants in Gran Canaria (Spain).
AB - The presence and fate of pharmaceutical residues in environmental samples are of
great interest. There is a vast number of studies published regarding their
input, presence, effects and risks in ecosystems. Moreover, it has been
demonstrated that the primary source of input of these contaminants in the
environment is from Wastewater Treatment Plants (WWTPs). It is therefore
essential to evaluate the efficiency of commonly used treatments and the
necessity of applying novel purification processes in order to eliminate or
reduce the concentration of pharmaceuticals from wastewater or from the effluent
of WWTPs. The aim of this work was to quantify twenty-three pharmaceutical
compounds in the aqueous phase at different stages of a conventional and a
natural WWTP situated in Gran Canaria (Spain). The results indicate concentration
levels in the range of 0.004+/-0.001 to 59.2+/-11.7MUgL-1 and 0.018+/-0.001 to
148+/-14.7MUgL-1 from conventional and natural WWTPs, respectively. Better
efficiency was, however, offered by the conventional WWTP with a removal median
of 99.7%. In addition, the impact on different aquatic organisms (algae, daphnids
and fish) was assessed in terms of risk quotients. The results reveal a possible
highly harmful effect towards organisms by gemfibrozil, ibuprofen and ofloxacin.
PMID- 28505886
TI - Modeling carbon emissions from urban traffic system using mobile monitoring.
AB - Comprehensive analyses of urban traffic carbon emissions are critical in
achieving low-carbon transportation. This paper started from the architecture
design of a carbon emission mobile monitoring system using multiple sets of
equipment and collected the corresponding data about traffic flow, meteorological
conditions, vehicular carbon emissions and driving characteristics on typical
roads in Shanghai and Wuxi, Jiangsu province. Based on these data, the emission
model MOVES was calibrated and used with various sensitivity and correlation
evaluation indices to analyze the traffic carbon emissions at microscopic,
mesoscopic and macroscopic levels, respectively. The major factors that influence
urban traffic carbon emissions were investigated, so that emission factors of CO,
CO2 and HC were calculated by taking representative passenger cars as a case
study. As a result, the urban traffic carbon emissions were assessed
quantitatively, and the total amounts of CO, CO2 and HC emission from passenger
cars in Shanghai were estimated as 76.95kt, 8271.91kt, and 2.13kt, respectively.
Arterial roads were found as the primary line source, accounting for 50.49%
carbon emissions. In additional to the overall major factors identified, the
mobile monitoring system and carbon emission quantification method proposed in
this study are of rather guiding significance for the further urban low-carbon
transportation development.
PMID- 28505887
TI - Emission and distribution of phosphine in paddy fields and its relationship with
greenhouse gases.
AB - Phosphine (PH3), as a gaseous phosphide, plays an important role in the
phosphorus cycle in ecosystems. In this study, the emission and distribution of
phosphine, carbon dioxide (CO2) and methane (CH4) in paddy fields were
investigated to speculate the future potential impacts of enhanced greenhouse
effect on phosphorus cycle involved in phosphine by the method of Pearson
correlation analysis and multiple linear regression analysis. During the whole
period of rice growth, there was a significant positive correlation between CO2
emission flux and PH3 emission flux (r=0.592, p=0.026, n=14). Similarly, a
significant positive correlation of emission flux was also observed between CH4
and PH3 (r=0.563, p=0.036, n=14). The linear regression relationship was
determined as [PH3]flux=0.007[CO2]flux+0.063[CH4]flux-4.638. No significant
differences were observed for all values of matrix-bound phosphine (MBP), soil
carbon dioxide (SCO2), and soil methane (SCH4) in paddy soils. However, there was
a significant positive correlation between MBP and SCO2 at heading, flowering and
ripening stage. The correlation coefficients were 0.909, 0.890 and 0.827,
respectively. In vertical distribution, MBP had the analogical variation trend
with SCO2 and SCH4. Through Pearson correlation analysis and multiple stepwise
linear regression analysis, pH, redox potential (Eh), total phosphorus (TP) and
acid phosphatase (ACP) were identified as the principal factors affecting MBP
levels, with correlative rankings of Eh>pH>TP>ACP. The multiple stepwise
regression model ([MBP]=0.456*[ACP]+0.235*[TP]-1.458*[Eh]-36.547*[pH]+352.298)
was obtained. The findings in this study hold great reference values to the
global biogeochemical cycling of phosphorus in the future.
PMID- 28505888
TI - Fipronil washoff to municipal wastewater from dogs treated with spot-on products.
AB - Fipronil and fipronil degradates have been reported in treated wastewater
effluent at concentrations that exceed USEPA Aquatic Life Benchmarks, posing a
potential risk to the surface waters to which they discharge. Fipronil is a
common insecticide found in spot-on flea and tick treatment products that have
the potential for down-the-drain transport and direct washoff into surface water.
Volunteers currently treating their dogs with a fipronil-containing spot-on
product were recruited. Dogs were washed either 2, 7, or 28days after product
application, and rinsate from 34 discrete bathing events were analyzed by LC
MS/MS for fipronil and fipronil degradates (collectively known as fiproles).
Total fipronil application dosage ranged from 67.1-410.0mg per dog following
manufacturers' recommendation based on dog body weight. Total mass of fiproles
measured in rinsate ranged from 3.6-230.6mg per dog (0.2 86.0% of mass applied).
Average percentage of fiproles detected in rinsate generally decreased with
increasing time from initial application: 21+/-22, 16+/-13, and 4+/-5%
respectively for 2, 7, and 28days post application. Fipronil was the dominant
fiprole, >63% of total fiproles for all samples and >92% of total fiproles in 2
and 7day samples. Results confirm a direct pathway of pesticides to municipal
wastewater through the use of spot-on products on dogs and subsequent bathing by
either professional groomers or by pet owners in the home. Comparisons of mass
loading calculated using California sales data and recent wastewater monitoring
results suggest fipronil-containing spot-on products are a potentially important
source of fipronil to wastewater treatment systems in California. This study
highlights the potential for other active ingredients (i.e., bifenthrin,
permethrin, etofenprox, imidacloprid) contained in spot-on and other pet products
(i.e., shampoos, sprays) to enter wastewater catchments through bathing
activities, posing a potential risk to the aquatic organisms downstream of
wastewater discharge.
PMID- 28505889
TI - Vegetation dynamics and responses to climate change and human activities in
Central Asia.
AB - Knowledge of the current changes and dynamics of different types of vegetation in
relation to climatic changes and anthropogenic activities is critical for
developing adaptation strategies to address the challenges posed by climate
change and human activities for ecosystems. Based on a regression analysis and
the Hurst exponent index method, this research investigated the spatial and
temporal characteristics and relationships between vegetation greenness and
climatic factors in Central Asia using the Normalized Difference Vegetation Index
(NDVI) and gridded high-resolution station (land) data for the period 1984-2013.
Further analysis distinguished between the effects of climatic change and those
of human activities on vegetation dynamics by means of a residual analysis trend
method. The results show that vegetation pixels significantly decreased for
shrubs and sparse vegetation compared with those for the other vegetation types
and that the degradation of sparse vegetation was more serious in the Karakum and
Kyzylkum Deserts, the Ustyurt Plateau and the wetland delta of the Large Aral Sea
than in other regions. The Hurst exponent results indicated that forests are more
sustainable than grasslands, shrubs and sparse vegetation. Precipitation is the
main factor affecting vegetation growth in the Kazakhskiy Melkosopochnik.
Moreover, temperature is a controlling factor that influences the seasonal
variation of vegetation greenness in the mountains and the Aral Sea basin.
Drought is the main factor affecting vegetation degradation as a result of both
increased temperature and decreased precipitation in the Kyzylkum Desert and the
northern Ustyurt Plateau. The residual analysis highlighted that sparse
vegetation and the degradation of some shrubs in the southern part of the Karakum
Desert, the southern Ustyurt Plateau and the wetland delta of the Large Aral Sea
were mainly triggered by human activities: the excessive exploitation of water
resources in the upstream areas of the Amu Darya basin and oil and natural gas
extraction in the southern part of the Karakum Desert and the southern Ustyurt
Plateau. The results also indicated that after the collapse of the Soviet Union,
abandoned pastures gave rise to increased vegetation in eastern Kazakhstan,
Kyrgyzstan and Tajikistan, and abandoned croplands reverted to grasslands in
northern Kazakhstan, leading to a decrease in cropland greenness. Shrubs and
sparse vegetation were extremely sensitive to short-term climatic variations, and
our results demonstrated that these vegetation types were the most seriously
degraded by human activities. Therefore, regional governments should strive to
restore vegetation to sustain this fragile arid ecological environment.
PMID- 28505890
TI - Functioning grouped soil microbial communities according to ecosystem type, based
on comparison of fallows and meadows in the same region.
AB - Predicting the composition and function of microbial communities at a bio
geographical scale, across ecosystems, is challenging. We compared six abandoned
fields to six meadows to see whether soil microbial community structure and
activity are more similar within the ecosystem type than between the types. We
implemented bacteria and fungi phylogenetic markers profiling, phospholipids
analysis, fluorescence counts of total bacteria and algae and microscopy of
arbuscular mycorrhizal fungi (AMF). The functional performance of microbial
communities was assessed using enzymes activity measurements as well as culturing
and incubation experiments. The studied fallows and meadows had similar biomass
and general structure of soil microbial communities. However, the AMF root
colonization frequency was higher in the meadows than in the fallows. The AMF
colonization was promoted in meadows characterised by lower availability of NO3-,
P and K as well as higher soil pH, which additionally hampered plant acquisition
of P at the P-limited ecosystem. Fallow and meadow microbial communities showed
characteristic functional traits. Meadow soils exhibited higher basal respiration
rate, while cellulose decomposition and nitrogen mineralization were faster in
fallows. Even when no major differences in community structure could have been
detected soil microbial communities adapted to local and/or instantaneous
environmental conditions and formed functionally-specific ecotypes. This work
points out the relevance of preserving meadows as reservoirs of plant diversity,
which cope excellent in nutrient depleted conditions and in mountain regions
thanks to microbial components of ecosystem.
PMID- 28505892
TI - Re: Oncologic Outcomes of Kidney-Sparing Surgery versus Radical
Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Systematic Review by
the EAU Non-Muscle Invasive Bladder Cancer Guidelines Panel.
PMID- 28505891
TI - Modelling sediment fluxes in the Danube River Basin with SWAT.
AB - Sediment management is of prior concern in the Danube Basin for provision of
economic and environmental services. This study aimed at assessing current (1995
2009) sediment fluxes of the Danube Basin with SWAT model and identifying
sediment budget knowledge gaps. After hydrologic calibration, hillslope gross
erosion and sediment yields were broadly calibrated using ancillary data
(measurements in plots and small catchments, and national and European erosion
maps). Mean annual sediment concentrations (SSC) from 269 gauging stations (2968
station-year entries; median 19mg/L, interquartile range IQR 10-36mg/L) were used
for calibrating in-stream sediments. SSC residuals (simulations-observations)
median was 2mg/L (IQR -14; +22mg/L). In the validation dataset (172 gauging
stations; 1457 data-entries, median 17mg/L, IQR 10-28), median residual was 9mg/L
(IQR -9; +39mg/L). Percent bias in an independent dataset of annual sediment
yields (SSY; 689 data-entries in 95 stations; median 52t/km2/y, IQR 20
151t/km2/y) was -21.5%. Overall, basin-wide model performance was considered
satisfactory. Sediment fluxes appeared overestimated in some regions (Sava and
Velika Morava), and underestimated in others (Siret-Prut and Romanian Danube),
but unbiased elsewhere. According to the model, most sediments were generated by
hillslope erosion. Streambank degradation contributed about 5% of sediments, and
appeared important in high stream power Alpine reaches. Sediment trapping in
reservoirs and floodplain deposition was probably underestimated and
counterbalanced by high stream deposition. Factor analysis showed that model
underestimations were correlated to Alpine and karst areas, whereas
underestimations occurred in high seismicity areas of the Lower Danube.
Contemporary sediment fluxes were about one third of values reported for the
1980s for several tributaries of the Middle and Lower Danube. Knowledge gaps
affecting the sediment budget were identified in the contributions of some
erosion processes (glacier erosion, gully erosion and mass movements), and in
stream sediment dynamics.
PMID- 28505893
TI - Re: Robot-Assisted vs Open Adrenalectomy: Evaluation of Cost-Effectiveness and
Peri-Operative Outcome.
PMID- 28505894
TI - Re: The Prognostic Significance of the Early Postoperative Neutrophil-to
Lymphocyte Ratio in Patients with Urothelial Carcinoma of the Bladder Undergoing
Radical Cystectomy.
PMID- 28505895
TI - Re: Cytokine Panel for Response to Intravesical Therapy (CyPRIT): Nomogram of
Changes in Urinary Cytokine Levels Predicts Patient Response to bacillus Calmette
Guerin.
PMID- 28505896
TI - Re: Advanced Small Cell Carcinoma of the Bladder: Clinical Characteristics,
Treatment Patterns and Outcomes in 960 Patients and Comparison with Urothelial
Carcinoma.
PMID- 28505897
TI - Re: National Trends in Prostate Biopsy and Radical Prostatectomy Volumes
following the US Preventive Services Task Force Guidelines against Prostate
Specific Antigen Screening.
PMID- 28505898
TI - Re: Mortality among Men with Advanced Prostate Cancer Excluded from the ProtecT
Trial.
PMID- 28505899
TI - Re: Urologist-Level Correlation in the Use of Observation for Low- and High-Risk
Prostate Cancer.
PMID- 28505900
TI - Re: Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation of
Prostate Tissue in Patients with Localized Prostate Cancer: A Prospective Phase 1
Clinical Trial.
PMID- 28505901
TI - Re: Activation of Notch1 Synergizes with Multiple Pathways in Promoting
Castration-Resistant Prostate Cancer.
PMID- 28505902
TI - Re: Robot-Assisted versus Open Radical Prostatectomy: A Contemporary Analysis of
an All-Payer Discharge Database.
PMID- 28505903
TI - Re: Androgen Receptor Antagonists Compromise T Cell Response against Prostate
Cancer Leading to Early Tumor Relapse.
PMID- 28505904
TI - Re: Spermatogenesis in Tumor-Bearing Testes in Germ Cell Testicular Cancer
Patients.
PMID- 28505905
TI - Re: Predictors of Sperm Recovery after Cryopreservation in Testicular Cancer.
PMID- 28505906
TI - Re: Incidence and Management of Uncomplicated Recurrent Urinary Tract Infections
in a National Sample of Women in the United States.
PMID- 28505907
TI - Re: Small Intestine Early Innate Immunity Response during Intestinal Colonization
by Escherichia coli Depends on its Extra-Intestinal Virulence Status.
PMID- 28505908
TI - Re: Policies for Replacing Long-Term Indwelling Urinary Catheters in Adults.
PMID- 28505909
TI - Re: Impact of Hair Removal on Surgical Site Infection Rates: A Prospective
Randomized Noninferiority Trial.
PMID- 28505910
TI - Re: A Randomised Phase I/II Trial to Evaluate the Efficacy and Safety of Orally
Administered Oxalobacter formigenes to Treat Primary Hyperoxaluria.
PMID- 28505911
TI - Re: Comprehensive Mutagenesis of the FimS Promoter Regulatory Switch Reveals
Novel Regulation of Type 1 Pili in Uropathogenic Escherichia coli.
PMID- 28505914
TI - Re: High-Frequency Dusting versus Conventional Holmium Laser Lithotripsy for
Intrarenal and Ureteral Calculi.
PMID- 28505913
TI - Re: Progress in Understanding the Genetics of Calcium-Containing Nephrolithiasis.
PMID- 28505912
TI - Re: The Effect of a Pure Anti-Inflammatory Therapy on Reducing Prostate-Specific
Antigen Levels in Patients Diagnosed with a Histologic Prostatitis.
PMID- 28505915
TI - Re: RNA Interference in the Treatment of Renal Stone Disease: Current Status and
Future Potentials.
PMID- 28505916
TI - Re: Factors Associated with Compliance in Submitting 24-Hour Urine Collections in
an Underserved Community.
PMID- 28505917
TI - Re: A Large Retrospective Series of Pregnancy and Delivery after Midurethral
Sling for Stress Urinary Incontinence.
PMID- 28505918
TI - Re: Electronic Bladder Diaries of Differing Duration versus a Paper Diary for
Data Collection in Overactive Bladder.
PMID- 28505920
TI - Re: Is Self-Reported Adherence Associated with Clinical Outcomes in Women Treated
with Anticholinergic Medication for Overactive Bladder?
PMID- 28505919
TI - Re: OnabotulinumtoxinA vs Sacral Neuromodulation on Refractory Urgency Urinary
Incontinence in Women: A Randomized Clinical Trial.
PMID- 28505921
TI - Re: Workforce Analysis of Female Pelvic Medicine and Reconstructive Surgery, 2015
to 2045.
PMID- 28505922
TI - Re: Transplanted Human Stem Cell-Derived Interneuron Precursors Mitigate Mouse
Bladder Dysfunction and Central Neuropathic Pain after Spinal Cord Injury.
PMID- 28505923
TI - Re: Lower Urinary Tract Symptoms and Metabolic Disorders: ICI-RS 2014.
PMID- 28505924
TI - Re: Impact of Incontinence on the Quality of Life of Caregivers of Older Persons
with Incontinence: A Qualitative Study in Four European Countries.
PMID- 28505925
TI - Re: Ten-Year Prevalence and Incidence of Urinary Incontinence in Older Women: A
Longitudinal Analysis of the Health and Retirement Study.
PMID- 28505926
TI - Re: Effectiveness of Solifenacin and Trospium for Managing of Severe Symptoms of
Overactive Bladder in Patients with Benign Prostatic Hyperplasia.
PMID- 28505927
TI - Re: Safety and Efficacy of Bipolar versus Monopolar Transurethral Resection of
the Prostate: A Comparative Study.
PMID- 28505928
TI - Re: Moxibustion as an Adjuvant for Benign Prostatic Hyperplasia with Lower
Urinary Tract Symptoms: A Protocol for a Parallel-Group, Randomised, Controlled
Pilot Trial.
PMID- 28505929
TI - Re: Interactions between Benign Prostatic Hyperplasia (BPH) and Prostate Cancer
in Large Prostates: A Retrospective Data Review.
PMID- 28505930
TI - Re: Testosterone Threshold for Increased Cardiovascular Risk in Middle-Aged and
Elderly Men: A Locally Weighted Regression Analysis.
PMID- 28505931
TI - Re: Skin Autofluorescence (a Marker for Advanced Glycation End Products) and
Erectile Dysfunction in Diabetes.
PMID- 28505932
TI - Re: Rasch Analysis of the Premature Ejaculation Diagnostic Tool (PEDT) and the
International Index of Erectile Function (IIEF) in an Iranian Sample of Prostate
Cancer Patients.
PMID- 28505933
TI - Re: Self-Reported Sitting Time and Prevalence of Erectile Dysfunction in Japanese
Patients with Type 2 Diabetes Mellitus: The Dogo Study.
PMID- 28505934
TI - Re: Hematospermia Evaluation at MR Imaging.
PMID- 28505935
TI - Re: Sexual Dysfunction among Females Receiving Psychotropic Medication: A
Hospital-Based Cross-Sectional Study.
PMID- 28505936
TI - Re: Relationship between Paternal Somatic Health and Assisted Reproductive
Technology Outcomes.
PMID- 28505937
TI - Re: Does Abstinence from Ejaculation before Prostate MRI Improve Evaluation of
the Seminal Vesicles?
PMID- 28505938
TI - Re: Cancer Risk in First- and Second-Degree Relatives of Men with Poor Semen
Quality.
PMID- 28505939
TI - Re: Influence of Increasing Body Mass Index on Semen and Reproductive Hormonal
Parameters in a Multi-Institutional Cohort of Subfertile Men.
PMID- 28505940
TI - Re: Treatment with Human, Recombinant FSH Improves Sperm DNA Fragmentation in
Idiopathic Infertile Men Depending on the FSH Receptor Polymorphism p.N680S: A
Pharmacogenetic Study.
PMID- 28505941
TI - Re: Novel Device for Male Infertility Screening with Single-Ball Lens Microscope
and Smartphone.
PMID- 28505942
TI - Re: Gaining Coverage in 2014: New Estimates of Marketplace and Medicaid
Transitions.
PMID- 28505943
TI - Re: Marketplace Plans with Narrow Physician Networks Feature Lower Monthly
Premiums than Plans with Larger Networks.
PMID- 28505944
TI - Re: The Changing Financial Landscape of Renal Transplant Practice: A National
Cohort Analysis.
PMID- 28505945
TI - Re: Penile Appearance after Hypospadias Correction from a Parent's Point of View:
Comparison of the Hypospadias Objective Penile Evaluation Score and Parents
Penile Perception Score.
PMID- 28505946
TI - Re: Clinical Pathway for Early Discharge after Complete Primary Repair of
Exstrophy and Epispadias by Using a Spica Cast.
PMID- 28505947
TI - Re: Reliance of Preoperative Scrotal Examination versus Final Operative Findings
in the Evaluation of Non-Palpable Testes.
PMID- 28505949
TI - Re: Undescended Testis: Level of Knowledge among Potential Referring Health-Care
Providers.
PMID- 28505948
TI - Re: Staged Laparoscopic Traction-Orchiopexy for Intraabdominal Testis (Shehata
Technique): Stretching the Limits for Preservation of Testicular Vasculature.
PMID- 28505950
TI - Prolotherapy: An effective therapy for Tietze syndrome.
AB - PURPOSE: To compare the short-term effect of prolotherapy and conservative terapy
for the Tietze syndrome. PATIENTS AND METHODS: From 2013 to 2014, twenty-one
patients underwent prolotherapy (group 1) and thirteen underwent conservative
therapy with analgesics (group 2). A visual analogue score (VAS) was recorded for
measurement of pain intensity in all patients before (Pre VAS) and after
injection first day (VAS1), first week (VAS2) and fourth week (VAS3). Group 2
were received systemic nonsteroidal anti-inflammatory drug. VAS score was
recorded similarly at the same times (Pre VAS, VAS1, VAS2, VAS3), and clinical
affects were compared between the two groups. RESULTS: The mean VAS score (mm)
before prolotherapy was 7.10 in patients who received prolotherapy, and 7.14 mm
in patients who treated nonsteroidal anti-inflammatory drug. The mean VAS after
the fist injection was 2.19 mm and dropped to 1.52 mm after the third injection.
The mean VAS after the nonsteroidal anti-inflammatory drug treatment dropped 2.62
mm and during the same scores to 3 weeks later. There was no significant
difference between the group 1 and group 2 in the age, sex and comorbidity. Also
there was no significant difference between the group 1 and group 2 in clinical
and radiological evidence. The prolotherapy group showed a faster recovery,
including significantly reduced clinic findings (p: 0.001). Third VAS is
significant finding for the prolotherapy group. CONCLUSION: Prolotherapy could be
performed safely and is a method with a favorable long term treatments for Tietze
Syndrome. It may be the ideal procedure for patients with drugs side effects and
advers events especially for those with limited liver and kidney reserve or
significant comorbidities.
PMID- 28505951
TI - Reliability of mechanomyographic amplitude measurements for trunk muscles during
maximal voluntary isometric contraction.
AB - BACKGROUND: Mechanomyography (MMG) has been used to investigate mechanical
characteristics of muscle contraction in clinical and experimental settings.
OBJECTIVE: The aim of this study was to determine the test-retest reliability of
mechanomyographic amplitude (MMGRMS) measurements as a tool for measuring the
maximal voluntary isometric contractions (MVICs) of trunk muscles in healthy
participants. METHODS: There were ten young adults participating in this study.
Accelerometers were used to detect surface MMG signals from three trials of 5-s
MVICs of the rectus abdominis, external obliques, erector spinae, and multifidus
in the vertical, transverse, and longitudinal directions. Intraclass correlation
coefficient (ICC), standard error of measurement (SEM), and minimum detectable
change were calculated. RESULTS: Good to excellent test-retest reliability of
mechanomyographic amplitude (MMGRMS) measurements was achieved for all MVICs of
trunk muscles in healthy participants, as indicated by ICCs ranging from 0.99 to
0.64 for MMGRMS of the trunk muscles during MVIC. CONCLUSIONS: This study
demonstrates that MMG is a reliable measurement to detect the activation
amplitudes of trunk muscles during MVIC.
PMID- 28505952
TI - Independent predictors of mortality in subacute and chronic stroke patients: A
single center study in Turkey.
AB - BACKGROUND: Although the long-term survival and related predictors have been
identified in stroke patients, there is little evidence about the mortality rates
and its associated factors in stroke patients treated in rehabilitation units.
OBJECTIVE: To evaluate 5-year mortality rates of patients with stroke and its
relationship with the clinical characteristics after inpatient subacute-chronic
rehabilitation. METHODS: The files of 1016 stroke patients (482 male, 534 female)
who received inpatient rehabilitation program were examined retrospectively.
Patients' characteristics and functional ambulation category were recorded at the
end of the rehabilitation program. The survival probability was estimated using
the Kaplan-Meier method and the univariate effects of predictors were determined
using the log-rank test. The possible factors determined with univariate analyses
were checked in the Cox regression analysis. RESULTS: A total of 273 patients
(32%) died within 5 years after stroke. Age (p< 0.001, RR: 1.06, 95% CI: 1.05
1.08), presence of coronary artery disease (p= 0.003, RR: 1.53, 95% CI: 1.16
2.03) and poor walking ability (p< 0.001, RR: 2.06, 95% CI: 1.49-2.86) were
independent prognostic factors for increased mortality. CONCLUSIONS: About one
third of the rehabilitation patients died within 5 years after stroke. As
independent ambulation was a strong predictor for long-term survival, it should
be provided via rehabilitation techniques. Future studies are proposed to
determine the effects of rehabilitation methods on mortality rates.
PMID- 28505953
TI - Understanding the complete pathophysiology of chronic mild to moderate neck pain:
Implications for the inclusion of a comprehensive sensorimotor evaluation.
AB - BACKGROUND: Inconsistencies in the literature concerning the effect of neck pain
have led to a lack of understanding concerning the complete pathophysiology of
neck pain. While the effect of neck pain on motor function as measured by active
range of motion and isometric neck strength is well documented the effect of neck
pain on sensory measures such as tactical acuity and neck reposition error (NRE)
remain poorly understood. OBJECTIVE: The purpose of this study was to evaluate a
combined sensorimotor evaluation to explore the potential benefits of
incorporating both sensory and motor task into a physical evaluation of neck pain
suffers to gain an added knowledge of the complete pathophysiology of their
health status. METHODS: A cross-sectional study that measured neck joint
reposition error, tactical acuity, neck isometric strength and range of motion in
40 volunteer participants (22 pain, 18 control). RESULTS: A statistically
significant increase in NRE in flexion (2.75?+/- 1.52? vs. 4.53?+/- 1.74? and in
extension (3.78?+/- 1.95? vs 5.77?+/- 2.73? in participants suffering from neck
pain was observed. Additionally, the dermatome C5 was found to be the most
affected. No differences were found in neck strength or neck range of motion
between healthy controls and patients with chronic moderate neck pain.
PMID- 28505954
TI - Manipulative rehabilitation applied soon after lumbar disc surgery improves late
post-operative functional disability: A preliminary 2-year follow-up study.
AB - BACKGROUND: Studies have shown late post-operative physical disability and
residual pain in patients following lumbar disc surgery despite growing evidence
of its beneficial effects. Therefore, rehabilitation is required to minimise the
late post-operative complications. OBJECTIVE: To assess the feasibility of
manipulative rehabilitation to improve late post-operative outcomes. METHODS:
Twenty-one patients aged 25-65 years undergoing lumbar microdiscectomy were
randomly assigned to the rehabilitation group (n= 14) or active control group (n=
7) by simple randomisation. Eight rehabilitation sessions were initiated 2-3
weeks after surgery. Thirty-minute sessions were conducted twice weekly for four
weeks. Post-operative physical disability and pain were assessed at baseline and
at the two-year follow-up. RESULTS: Post-operative physical disability improved
more in patients who had undergone rehabilitation than in those who had received
control care (63% vs. -23%, P< 0.05). Post-operative residual low back and leg
pain were alleviated in the treatment group (26% and 57%, respectively), but
intensified in the control group (-5% and -8%, respectively). CONCLUSIONS: This
study demonstrated the potential of manipulative rehabilitation and importance of
post-operative management after lumbar disc surgery. Definitive trials with
larger sample sizes are required to confirm the feasibility and potential
therapeutic effectiveness of this approach.
PMID- 28505955
TI - The immediate effects of manual stretching and cervicothoracic junction
manipulation on cervical range of motion and upper trapezius pressure pain
thresholds.
AB - INTRODUCTION: Myofascial pain is a common impairment treated with various manual
interventions including spinal thrust manipulation and stretching; however, the
comparative efficacy of each intervention is uncertain. Therefore, the purpose of
this investigation was to evaluate thrust manipulation targeting the
cervicothoracic junction compared to a manual stretch of the upper trapezius
muscle on cervical range of motion and upper trapezius pressure pain thresholds
(PPTs). METHODS: Healthy participants with no significant history of neck pain
were randomized into a thrust manipulation group, a stretching group, or a
control group. Within group differences were evaluated via a dependent t-test,
and group by time interactions were evaluated by a two-way repeated measures
ANOVA. RESULTS: One hundred and two participants were recruited to participate.
Baseline demographics revealed no significant differences between groups.
Significant group by time interactions were found for changes in PPTs for both
the right and left upper trapezius. Also, significant differences were found for
changes in cervical extension, as well as right and left cervical side bending
favoring the treatment groups. DISCUSSION: This study demonstrates the potential
independent effectiveness of spinal thrust manipulation or stretching for
reducing PPTs at the upper trapezius. Future research should further evaluate the
limitation of PPTs as a measure of muscle sensitivity as well as factors that may
contribute to variability in the measurements among individuals seeking care.
PMID- 28505956
TI - Regression of lumbar disc herniation by physiotherapy. Does non-surgical spinal
decompression therapy make a difference? Double-blind randomized controlled
trial.
AB - BACKGROUND AND OBJECTIVES: The aim of the study determining whether or not Non
invasive Spinal Decompression Therapy (NSDT) was effective in resorption of
herniation, increasing disc height in patients with lumbar disc herniation
(LHNP). METHODS: A total of twenty patients diagnosed as LHNP and suffering from
pain at least 8 weeks were enrolled to the study. Patients were allocated in
study (SG) and control groups (CG) randomly. Both groups received combination of
electrotherapy, deep friction massage and stabilization exercise for fifteen
session. SG received additionally NSDT different from CG. Numeric Anolog Scale,
Straight leg raise test, Oswestry Disability Index (ODI) were applied at baseline
and after treatment. Disc height and herniation thickness were measured on
Magnetic Resonance Imagination which performed at baseline and three months after
therapy. RESULTS: Both treatments had positive effect for improving pain,
functional restoration and reduction in thickness of herniation. Although
reduction of herniation size was higher in SG than CG, no significant differences
were found between groups and any superiority to each other (p> 0.05).
CONCLUSIONS: This study showed that patients with LHNP received physiotherapy had
improvement based on clinical and radiologic evidence. NSDT can be used as
assistive agent for other physiotherapy methods in treatment of lumbar disc
herniation.
PMID- 28505958
TI - Lateral ankle pain and peroneal tendon subluxation in a patient with peroneal
quartus muscle and superior peroneal retinaculum injury.
PMID- 28505957
TI - Spindle cell type malignant peripheral nerve sheath tumor arising in benign
schwannoma with multiple intraosseous spinal metastasis: A case report.
AB - BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) arising in benign
schwannoma with multiple intraosseous spinal metastasis is extremely rare, having
a highly aggressive progression and poor prognosis. In such cases, the malignant
cells of MPNST usually have an epithelioid morphology. Here, the authors present
a very rare case of spindle cell type MPNST arising in benign schwannoma. CASE: A
47-year-old woman had a history of wide marginal excision of right buttock
spindle cell sarcoma previously. However, metastatic lesions to C7, L1 body, and
the right lung were detected during follow-up. Total spondylectomy and
stabilization of the C7 and L1 tumors were performed within an interval of 5
months. However, the patient expired 6 months after the last surgery. From
analysis and study of three tumor specimens (right buttock, cervical and lumbar
spine), the pathological diagnosis based on histomorphologic and
immunohistochemical studies was spindle cell sarcoma, high grade, most consistent
with MPNST arising in schwannoma. RESULTS: It is important that pathologists and
surgeons recognize that spindle cell type MPNST may arise in benign schwannoma,
as this recognition aids in assessment of patients with schwannoma and
contributes to the pathologist making a more precise diagnosis, and the surgeon
better determining the appropriate therapeutic options and surgical methods.
PMID- 28505959
TI - The application of a pre-positioned upper cervical traction mobilization to
patients with painful active cervical rotation impairment: A case series.
AB - BACKGROUND: Cervical mobilization and manipulation have been shown to improve
cervical range of motion and pain. Cervical rotatory thrust manipulation has been
associated with adverse patient reaction and damage to the V3 segment of the
vertebral artery (VA). OBJECTIVE: To document and describe the effects of an
upper cervical (UC) traction based mobilization on participants with restricted
and painful cervical rotation and to document if the mobilization changed blood
flow velocity through the vertebral artery. METHODS: This case series examined
the effects of a traction based spinal mobilization on two different groups of
participants. Group I included 93 participants with restricted bilateral cervical
rotation that was also painful at end range. Group II included 30 different
participants whose VA blood flow velocity was examined during the same
mobilization. Pre- and post-mobilization active cervical rotation, pain intensity
levels, and VA blood flow velocity during mobilization was documented. RESULTS:
Paired T-tests were used to determine statistical significance for changes in
cervical rotation, and VA blood flow velocity during mobilization. Ninety-three
participants in group I demonstrated an average increase of 16 degrees of
cervical rotation. No participant demonstrated an increase in pain, and no
participant in group II (N= 30) demonstrated a change in VA blood flow velocity.
CONCLUSIONS: The application this UC traction based mobilization improved active
cervical rotation, end range rotation pain response, did not cause pain during
its application and did not alter blood flow through the VA during application.
PMID- 28505960
TI - Normal aging of the lumbar spine in women.
AB - BACKGROUND: Lumbar lordosis is required for bipedalism. OBJECTIVES: To
investigate age-related changes in lumbar lordosis and to clarify the
relationships between lumbar lordosis and vertebral wedging and disc
degeneration. METHODS: A total of 300 women were included in this retrospective
study, 50 in each of six age groups (20-, 30-, 40-, 50-, 60- and 70-year-olds).
Patients with vertebral collapse, instable fracture or disc sequestration were
excluded. In each patient, lumbar lordosis angle, posterior vertebral wedging, L5
S1 intervertebral disc angle, L5/L1 vertebral height ratio and L5-S1
intervertebral disc/L1-L2 intervertebral disc height ratio were examined.
Significance level was set at p< 0.05 and two-sided tests were used. RESULTS:
Significant differences were found in lumbar lordosis according to age group (p<
0.001). Lumbar lordosis correlated most strongly with L4 posterior vertebral
wedging, L5 posterior vertebral wedging and L5-S1 intervertebral disc angle, in
that order (r= 0.50, r= 0.40, r= 0.32, respectively; p< 0.001). CONCLUSION: In
this cohort, strong spinal structure was maintained during physiological aging
from 20 to 40 years of age; lumbar lordosis increased by 50 years of age.
Increased lordosis correlated with increased posterior vertebral wedging and loss
of posterior disc height.
PMID- 28505961
TI - Effects of dual-task conditions on cervical spine movement variability.
AB - BACKGROUND: The potential to accurately perform cervical movements during more
challenging tasks might be of importance to prevent dysfunctional motion
characteristics. Although sensorimotor function during dual-task conditions are
of increasing interest in biomedical and rehabilitation research, effects of such
conditions on movement consistency of the neck have not yet been investigated.
OBJECTIVE: In this crossover MiSpEx(Medicine in Spine Exercise)-diagnostic study,
we aimed to explore differences between single and dual-task conditions on
cervical movement variability. METHODS: Nineteen healthy participants (9 male;
24.5 +/- 3.3 y) performed 10 repetitive maximal cervical movements in (1)
flexion/extension and (2) lateral flexion, during one single- and during two dual
task test conditions (cognitive, motor) in a randomised and cross-over sequence.
Latter consisted of a working memory n-back task (n= 2) and a repetitive ankle
movement task. Range of motion (RoM) was assessed using an external three
dimensional ultrasonic movement analysis system. Coefficient of variation (CV)
for repetitive RoM was analysed for differences between conditions and controlled
for variances in intra-individual movement characteristics. RESULTS: Friedman and
post-hoc Bonferroni-adjusted confidence intervals for differences from single- to
dual-task values revealed changes in CV in flexion/extension from single-task to
motor dual-task (+0.02 +/- 0.02 (97.5%CI: 0.01; 0.03); p< 0.05) but not to
cognitive dual-task condition (+0.01 +/- 0.02 (97.5%CI: 0.003; 0.02)) nor for
lateral flexion (p> 0.05). Pearson regression analyses revealed a linear negative
(p< 0.01) influence of CV in flexion/extension on differences from single to both
cognitive (R=2 0.47) and motor dual-task (R=2 0.55). Results for lateral flexion
are comparable, baseline CV negatively impacts differences to cognitive (R=2 0.2)
and motor dual-task performance (R=2 0.76; p< 0.01). CONCLUSIONS: Participants
with comparable low cervical CV at single-task display a profound increase during
dual-task conditions while participants with a higher variability remained almost
stable or showed a decrease. The results point toward a complex interrelationship
of motion patterns and adaptation processes during challenging tasks in respect
of cervical CV.
PMID- 28505962
TI - Assessment of body parameters' symmetry in child violinists.
AB - BACKGROUND: Playing violin may lead to overload of the locomotor system.
OBJECTIVE: The aim of this study was to assess body parameters for trunk symmetry
in child violinists and compare with the control group. METHODS: We analyzed body
posture of 101 children aged 7-12 years, mean age 11.09 +/- 9.46, 49 child
violinists and control group of 52 children. RESULTS: We found statistically
significant differences for the difference in depth of the lower corners of
scapulae and upper posterior spina iliaca, though greater asymmetries were found
in the clinical control group. The remaining parameter values are close to
significance, which may suggest that the process of postural change among the
children had just started and that the existing asymmetries were easy to correct.
We found positive correlation between body height and the difference in distance
of the lower corners of scapulae from the spine: OL (p= 0.029, correlation
coefficient value was 0.167) and the Thales triangle height: (p= 0.018,
correlation coefficient was 0.214). CONCLUSIONS: Position maintained while
playing the violin changed some parameters characterizing the curvature of the
spine in frontal plane. We found the importance of detailed analysis of children
body posture and its critical assessment.
PMID- 28505963
TI - Trunk muscle activation levels during eight stabilization exercises used in the
functional kinetics concept: A controlled laboratory study.
AB - BACKGROUND: To ensure accurate implementation of stabilization exercises in
rehabilitation, physical therapists need to understand the muscle activation
patterns of prescribed exercise. OBJECTIVE: Compare muscle activity during eight
trunk and lumbar spine stabilization exercises of the Functional Kinetics concept
by Klein-Vogelbach. METHODS: A controlled laboratory study with a single-group
repeated-measures design was utilized to analyze surface electromyographic
intensities of 14 female and 6 male young healthy participants performing eight
exercises. Data were captured from the rectus abdominis, external/internal
oblique and lumbar paraspinalis. The normalized muscle activation levels (maximum
voluntary isometric contraction, MVIC) for three repetitions during each exercise
and muscle were analyzed. RESULTS: Side bridging (28 +/- 20%MVIC) and advanced
planking (29 +/- 20%MVIC) reached the highest activity in the rectus abdominis.
For external and internal oblique muscles, side bridging also showed the greatest
activity of 99 +/- 36%MVIC and 52 +/- 25%MVIC, respectively. Apart from side
bridging (52 +/- 14%MVIC), the supine roll-out (31 +/- 12%MVIC) and prone roll
out (31 +/- 9%MVIC) showed the greatest activity for the paraspinalis. The
advanced quadruped, seated back extension and flexion on chair/Swiss Ball, prone
roll-out and advanced one-leg back bridging only yielded negligible muscle
activities for the rectus abdominis (< 5%MVIC). CONCLUSION: Based on the data
obtained, recommendations for selective trunk muscle activation during eight
stabilization exercises were established, which will guide physical therapists in
the development of exercises tailored to the needs of their patients.
PMID- 28505965
TI - Determining the IgM and IgG antibody titer against CMV and helicobacter pylori in
the serum of multiple sclerosis patients comparing to the control group in
Hamadan.
AB - BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease that disables
central nervous system (CNS) system. Cytomegalovirus (CMV) probably has an
important role in the MS pathology. The infection with helicobacter pylori also
is recognized as a protective agent against MS in female. METHODS: Serum samples
were isolated and frozen at -70?C. The earlier mentioned anti-virus antibodies
and antibacterial antibodies were quantified by Elisa kit. RESULTS: The results
showed that IgG antibody average value against cytomegalovirus in the blood of
multiple sclerosis patients not only decreased but also was significant
statistically (p< 0.05). IgM and IgG antibodies average value in the blood of
multiple sclerosis patients against helicobacter pylori shown a statistically
significant decrease (p< 0.05). CONCLUSION: Therefore it may be considered that
probably helicobacter pylori presence in the individuals especially in female can
alleviate MS signs. CMV infection can intensify the symptoms in multiple
sclerosis patients.
PMID- 28505966
TI - On the antigen-antibody interaction: A thermodynamic consideration.
AB - Despite its relevance to many biomedical fields, relatively little effort has
been put into a comprehensible quantitative description of the effect of reaction
temperature on the interaction between antigens and their antibodies. In this
article, a novel, straightforward mathematical model is proposed, which aims to
describe the effect of temperature on antigen-antibody kinetics. The model
proposed in this article could hopefully provide clinicians, immunologists, and
biochemists with an improved insight into the kinetic effect of fluctuations in
reaction temperature on antigen-antibody-dependent processes and therefore into
the kinetics of the humoral adaptive immune response.
PMID- 28505968
TI - Inflammation, Amyloid, and Atrophy in The Aging Brain: Relationships with
Longitudinal Changes in Cognition.
AB - Amyloid deposition occurs in aging, even in individuals free from cognitive
symptoms, and is often interpreted as preclinical Alzheimer's disease (AD)
pathophysiology. YKL-40 is a marker of neuroinflammation, being increased in AD,
and hypothesized to interact with amyloid-beta (Abeta) in causing cognitive
decline early in the cascade of AD pathophysiology. Whether and how Abeta and YKL
40 affect brain and cognitive changes in cognitively healthy older adults is
still unknown. We studied 89 participants (mean age: 73.1 years) with
cerebrospinal fluid samples at baseline, and both MRI and cognitive assessments
from two time-points separated by two years. We tested how baseline levels of
Abeta42 and YKL-40 correlated with changes in cortical thickness and cognition.
Thickness change correlated with Abeta42 only in Abeta42+ participants (<600
pg/mL, n = 27) in the left motor and premotor cortices. Abeta42 was unrelated to
cognitive change. Increased YKL-40 was associated with less preservation of
scores on the animal naming test in the total sample (r = -0.28, p = 0.012) and
less preservation of a score reflecting global cognitive function for Abeta42+
participants (r = -0.58, p = 0.004). Our results suggest a role for inflammation
in brain atrophy and cognitive changes in cognitively normal older adults, which
partly depended on Abeta accumulation.
PMID- 28505967
TI - NFATc2 Modulates Microglial Activation in the AbetaPP/PS1 Mouse Model of
Alzheimer's Disease.
AB - Alzheimer's disease (AD) brains are characterized by fibrillar amyloid-beta
(Abeta) peptide containing plaques and associated reactive microglia. The
proinflammatory phenotype of the microglia suggests that they may negatively
affect disease course and contribute to behavioral decline. This hypothesis
predicts that attenuating microglial activation may provide benefit against
disease. Prior work from our laboratory and others has characterized a role for
the transcription factor, nuclear factor of activated T cells (NFAT), in
regulating microglial phenotype in response to different stimuli, including Abeta
peptide. We observed that the NFATc2 isoform was the most highly expressed in
murine microglia cultures, and inhibition or deletion of NFATc2 was sufficient to
attenuate the ability of the microglia to secrete cytokines. In order to
determine whether the NFATc2 isoform, in particular, was a valid immunomodulatory
target in vivo, we crossed an NFATc2-/- line to a well-known AD mouse model, an
AbetaPP/PS1 mouse line. As expected, the AbetaPP/PS1 x NFATc2-/- mice had
attenuated cytokine levels compared to AbetaPP/PS1 mice as well as reduced
microgliosis and astrogliosis with no effect on plaque load. Although some
species differences in relative isoform expression may exist between murine and
human microglia, it appears that microglial NFAT activity is a viable target for
modulating the proinflammatory changes that occur during AD.
PMID- 28505969
TI - Early Detection of Learning Difficulties when Confronted with Novel Information
in Preclinical Alzheimer's Disease Stage 1.
AB - We employed a highly demanding experimental associative learning test (the AFE-T)
to explore memory functioning in Preclinical Alzheimer's Disease stage 1 (PreAD
1) and stage 2 (PreAD-2). The task consisted in the learning of unknown
object/name pairs and our comprehensive setup allowed the analysis of learning
curves, immediate recall, long-term forgetting rates at one week, three months,
and six months, and relearning curves. Forty-nine cognitively healthy subjects
were included and classified according to the presence or absence of abnormal CSF
biomarkers (Control, n = 31; PreAD-1, n = 14; PreAD-2, n = 4). Control and PreAD
1 performances on the experimental test were compared by controlling for age and
education. These analyses showed clear learning difficulties in PreAD-1 subjects
(F = 6.98; p = 0.01). Between-group differences in long-term forgetting rates
were less notable, reaching statistical significance only for the three-month
cued forgetting rate (F = 4.83; p = 0.03). Similarly, relearning sessions showed
only statistical trends between the groups (F = 3.22; p = 0.08). In the whole
sample, significant correlations between CSF Abeta42/tau ratio and the AFE-T were
found, both in the total learning score (r = 0.52; p < 0.001) and in the three
month cued forgetting rate (r = -0.38; p < 0.01). Descriptive subanalyses
involving PreAD-2 suggested greater learning and recall difficulties in these
subjects when compared with the PreAD-1 group. The present results suggest that
explicit learning difficulties when binding information could be one of the
earliest signs of the future emergence of episodic memory difficulties on the
Alzheimer's disease continuum. Our findings indicate that the AFE-T is a
sensitive test, capable of detecting subtle memory difficulties in PreAD-1.
PMID- 28505970
TI - Efficacy of Antidepressants for Depression in Alzheimer's Disease: Systematic
Review and Meta-Analysis.
AB - BACKGROUND: Depression is common in people with Alzheimer's disease (AD)
affecting overall outcomes and decreasing quality of life. Although depression in
AD is primarily treated with antidepressants, there are few randomized controlled
trials (RCTs) assessing efficacy and results have been conflicting. OBJECTIVES:
To systematically review evidence on efficacy of antidepressant treatments for
depression in AD. METHODS: Systematic review and meta-analysis of double blind
RCTs comparing antidepressants versus placebo for depression in AD. We searched
MEDLINE, CINAHL, EMBASE, PsycINFO, the Cochrane Controlled Trials Register and on
line national and international registers. Primary outcomes were treatment
response and depressive symptoms. Secondary outcomes were cognition,
acceptability, and tolerability. Risk of bias was also assessed. RESULTS: Seven
studies met inclusion criteria. Three compared sertraline with placebo; one
compared both sertraline and mirtazapine to placebo; imipramine, fluoxetine, and
clomipramine were evaluated in one study each. In terms of response to treatment
(6 studies, 297 patients treated with antidepressants and 223 with placebo), no
statistically significant difference between antidepressants and placebo was
found (odds ratio (OR) 1.95, 95% CI 0.97-3.92). We found no significant drug
placebo difference for depressive symptoms (5 studies, 311 patients, SMD -0.13;
95% CI -0.49 to 0.24). Overall quality of the evidence was moderate because of
methodological limitations in studies and the small number of trials. CONCLUSION:
Despite the importance of depression in people with AD, few RCTs are available on
efficacy of antidepressants, limiting clear conclusions of their potential role.
There is a need for further high quality RCTs.
PMID- 28505972
TI - Alzheimer's Disease-Associated Cerebrospinal Fluid (CSF) Biomarkers do not
Correlate with CSF Volumes or CSF Production Rate.
AB - BACKGROUND: Neuropathologically, Alzheimer's disease (AD) is characterized by
accumulation of a 42 amino acid peptide called amyloid-beta (Abeta42) in
extracellular senile plaques together with intraneuronal inclusions of
hyperphosphorylated tau protein in neurofibrillary tangles and neuronal
degeneration. These changes are reflected in the cerebrospinal fluid (CSF), the
volumes and production rates of which vary considerably between individuals, by
reduced concentration of Abeta42, increased concentration of phosphorylated tau
(P-tau) protein, and increased concentration of total tau (T-tau) protein,
respectively. OBJECTIVE: To examine the outstanding question if CSF
concentrations of AD associated biomarkers are influenced by variations in CSF
volumes, CSF production rate, and intracranial pressure in healthy individuals.
METHODS: CSF concentrations of Abeta42, P-tau, and T-tau, as well as a number of
other AD-related CSF biomarkers were analyzed together with intracranial
subarachnoid, ventricular, and spinal CSF volumes, as assessed by magnetic
resonance imaging volumetric measurements, and CSF production rate in 19
cognitively normal healthy subjects (mean age 70.6, SD 3.6 years). RESULTS:
Negative correlations were seen between the concentrations of three CSF
biomarkers (albumin ratio, Abeta38, and Abeta40), and ventricular CSF volume, but
apart from this finding, no significant correlations were observed. CONCLUSION:
These results speak against inter-individual variations in CSF volume and
production rate as important confounds in the AD biomarker research field.
PMID- 28505971
TI - Lipid Peroxidation Markers in Coronary Artery Disease Patients with Possible
Vascular Mild Cognitive Impairment.
AB - This study examined associations between lipid peroxidation markers and
cognition, and associations between these markers and cognitive response to an
exercise intervention program, in adults with coronary artery disease at risk of
dementia. Lipid peroxidation products were measured in serum in 118 patients (29
possible vascular mild cognitive impairment and 89 controls). Ratios of early-
(lipid hydroperoxides, LPH) to late-stage (8-isoprostane, 8-ISO; 4-hydroxy-2
nonenal, 4-HNE) lipid peroxidation products were calculated. Cognitive
performance was assessed before and at completion of a 24-week exercise
intervention program. A global effect of group on lipid peroxidation markers was
observed, adjusting for sex, years of education, and cardiopulmonary fitness
(main effect of group F (3,102) = 2.957, p = 0.036). Lower lipid peroxidation at
baseline, as determined by lower 8-ISO concentration, was associated with greater
improvement in verbal memory (F (1, 64) = 4.738, p = 0.03) and executive function
(F (1, 64) = 5.219, p = 0.026) performance. Similarly, higher ratios of 8-ISO/LPH
(F (1, 65) = 6.592, p = 0.013) and (8-ISO+4-HNE) to LPH (F (1, 65) = 3.857, p =
0.054), were associated with less improvement in executive function performance
over a 24-week exercise intervention. Lipid peroxidation may be a biomarker of
early vascular cognitive impairment, and elevated lipid peroxidation might limit
the cognitive benefits of exercise in this high-risk population.
PMID- 28505974
TI - State of Play in Alzheimer's Disease Genetics.
AB - Alzheimer's disease (AD), the main form of dementia in the elderly, is the most
common progressive neurodegenerative disease characterized by rapidly progressive
cognitive dysfunction and behavior impairment. AD exhibits a considerable
heritability and great advances have been made in approaches to searching the
genetic etiology of AD. In AD genetic studies, methods have developed from
classic linkage-based and candidate-gene-based association studies to genome-wide
association studies (GWAS) and next generation sequencing (NGS). The
identification of new susceptibility genes has provided deeper insights to
understand the mechanisms underlying AD. In addition to searching novel genes
associated with AD in large samples, the NGS technologies can also be used to
shed light on the 'black matter' discovery even in smaller samples. The shift in
AD genetics between traditional studies and individual sequencing will allow
biomaterials of each patient as the central unit of genetic studies. This review
will cover genetic findings in AD and consequences of AD genetic findings.
Firstly, we will discuss the discovery of mutations in APP, PSEN1, PSEN2, APOE,
and ADAM10. Then we will summarize and evaluate the information obtained from
GWAS of AD. Finally, we will outline the efforts to identify rare variants
associated with AD using NGS.
PMID- 28505975
TI - Reduced Cardiovascular Functions in Patients with Alzheimer's Disease.
AB - Previous studies have suggested that cardiovascular functions might play a
critical role in Alzheimer's disease (AD) pathogenesis. However, the relationship
among heart function, blood flow of cerebral vessels, and AD remains unclear. In
the present study, AD patients (n = 34) and age- and gender-matched cognitively
normal controls (n = 34) were recruited. Demographic and comorbidity information
was collected. The ejection fraction was measured using echocardiography, and the
mean velocity, pulsatility index (PI), and resistance index (RI) of the basilar
artery (BA), left terminal internal carotid artery (LTICA), and right terminal
internal carotid artery (RTICA) were measured using transcranial Doppler. The
data of lacunae, white matter changes, and plaques in the aortic arch and carotid
arteries were collected from brain magnetic resonance imaging and computed
tomography angiography images. Compared with normal controls, AD patients had
lower ejection fractions and cerebral blood flow velocities and higher RI and PI
in the BA, LTICA, and RTICA, as well as more plaques in the aortic and carotid
arteries. In the multivariate logistic regression analysis, the ejection fraction
and the mean velocity of the BA and LTICA were independently associated with AD
after adjusting for age, gender, education, vascular risk factors, arterial
plaques, and brain ischemic lesions detected in the brain images. These findings
suggest that heart function and vascular condition may play important roles in AD
pathogenesis. Improving cardiovascular functions could be a promising approach
for the prevention and treatment of AD.
PMID- 28505973
TI - Vitamin D Insufficiency and Cognitive Function Trajectories in Older Adults: The
Rancho Bernardo Study.
AB - BACKGROUND: Evidence of a role for vitamin D (VitD) in cognitive aging is mixed
and based primarily on extreme VitD deficiency. We evaluated the association of
VitD insufficiency with cognitive function in older, community-dwelling adults
living in a temperate climate with year-round sunshine. METHODS: A population
based longitudinal study of 1,058 adults (median age 75; 62% women) who had
cognitive function assessed and serum levels of 25-hydroxyvitaminD (25OHD)
measured in 1997-99 and were followed for up to three additional cognitive
function assessments over a 12-year period. RESULTS: Overall, 14% (n = 145) of
participants had VitD insufficiency defined as 25OHD <30 ng/ml. Adjusting for
age, sex, education, and season, VitD insufficiency was associated with poorer
baseline performance on the Mini-Mental Status Exam (MMSE) (p = 0.013), Trails
Making Test B (Trails B) (p = 0.015), Category Fluency (p = 0.006), and Long Term
Retrieval (p = 0.019); differences were equivalent to 5 years of age. For those
with VitD insufficiency, the odds of mildly impaired performance at baseline were
38% higher for MMSE (p = 0.08), 78% higher for Trails B (p = 0.017), and 2-fold
higher for Category Fluency and Long Term Retrieval (both p = 0.001). VitD
insufficiency was not related to the rate of cognitive decline on any test or the
risk of developing impaired performance during follow-up. CONCLUSION: In this
population with little VitD deficiency, even moderately low VitD was associated
with poorer performance on multiple domains of cognitive function. Low VitD did
not predict 12-year cognitive decline. Clinical trials are essential to establish
a causal link between VitD and cognitive well-being.
PMID- 28505976
TI - In Vivo Detection of Gray Matter Neuropathology in the 3xTg Mouse Model of
Alzheimer's Disease with Diffusion Tensor Imaging.
AB - A diagnosis of Alzheimer's disease (AD), a neurodegenerative disorder accompanied
by severe functional and cognitive decline, is based on clinical findings, with
final confirmation of the disease at autopsy by the presence of amyloid-beta
(Abeta) plaques and neurofibrillary tangles. Given that microstructural brain
alterations occur years prior to clinical symptoms, efforts to detect brain
changes early could significantly enhance our ability to diagnose AD sooner.
Diffusion tensor imaging (DTI), a type of MRI that characterizes the magnitude,
orientation, and anisotropy of the diffusion of water in tissues, has been used
to infer neuropathological changes in vivo. Its utility in AD, however, is still
under investigation. The current study used DTI to examine brain regions
susceptible to AD-related pathology; the cerebral cortex, entorhinal cortex, and
hippocampus, in 12-14-month-old 3xTg AD mice that possess both Abeta plaques and
neurofibrillary tangles. Mean diffusivity did not differ between 3xTg and control
mice in any region. Decreased fractional anisotropy (p < 0.01) and axial
diffusivity (p < 0.05) were detected only in the hippocampus, in which both
congophilic Abeta plaques and hyperphosphorylated tau accumulation, consistent
with neurofibrillary tangle formation, were detected. Pathological tau
accumulation was seen in the cortex. The entorhinal cortex was largely spared
from AD-related neuropathology. This is the first study to demonstrate DTI
abnormalities in gray matter in a mouse model of AD in which both pathological
hallmarks are present, suggesting the feasibility of DTI as a non-invasive means
of detecting brain pathology in vivo in early-stage AD.
PMID- 28505977
TI - Hippocampal and Clinical Trajectories of Mild Cognitive Impairment with Suspected
Non-Alzheimer's Disease Pathology.
AB - Suspected non-Alzheimer's disease pathology (SNAP) characterizes individuals
showing neurodegeneration (e.g., hypometabolism) without amyloid-beta (Abeta).
Findings from previous studies regarding clinical and structural trajectories of
SNAP are inconsistent. Using data from the Alzheimer's Disease Neuroimaging
Initiative, patients with amnestic mild cognitive impairment (MCI) were
categorized into four groups: amyloid positive with hypometabolism (Abeta+ND+),
amyloid only (Abeta+ND-), neither amyloid nor hypometabolism (Abeta-ND-), and
SNAP (Abeta-ND+). Abeta+ND+(n = 33), Abeta+ND-(n = 32), and Abeta-ND-(n = 36)
were matched to SNAP for age, gender, apolipoprotein E4 (apoE4) genotype, and
scores on the Montreal Cognitive Assessment. Elderly controls (n = 40) were also
matched to SNAP for age, gender, and apoE4 genotype. Longitudinal changes were
compared across groups in terms of hippocampal volume, clinical symptoms, daily
functioning, and cognitive functioning over a 2-year period. At baseline, no
difference in cognition and functioning was observed between SNAP and
Abeta+groups. SNAP showed worse clinical symptoms and impaired functioning at
baseline compared to Abeta-ND-and controls. Two years of follow-up showed no
differences in hippocampal volume changes between SNAP and any of the comparison
groups. SNAP showed worse functional deterioration in comparison to Abeta-ND-and
controls. However, Abeta+ND+ showed more severe changes in clinical symptoms in
comparison to SNAP. Thus, patients with MCI and SNAP showed 1) more severe
functional deterioration compared to Abeta-ND-and controls, 2) no differences
with Abeta+ND-, and 3) less cognitive deterioration than Abeta+ND+. Future
studies should investigate what causes SNAP, which is different from typical AD
pathology and biomarker cascades.
PMID- 28505978
TI - An Arabic Version of the Cognitive Subscale of the Alzheimer's Disease Assessment
Scale (ADAS-Cog): Reliability, Validity, and Normative Data.
AB - The Alzheimer's Disease Assessment Scale's cognitive subscale (ADAS-Cog) is the
most widely used instrument for screening cognitive dysfunction in Alzheimer's
disease. The aim of the present study was to develop an Arabic version of this
scale (A-ADAS-Cog), examine its psychometric properties (reliability and
validity), and provide normative data. The A-ADAS-Cog), an Arabic version of the
Mini-Mental State Examination (A-MMSE), and a Standardized Clinical Dementia
Rating Scale (CDR) were administered to three Tunisian groups: 124 normal
controls (NC), 33 patients with non-Alzheimer dementia (N-AD), and 25 patients
with Alzheimer's disease (AD). The A-ADAS-Cog scores were significantly affected
by age and education. A correction table was constructed to control these
effects. The results showed that the A-ADAS-Cog has good internal consistency and
reliability (alpha= 0.82 for AD). The test-retest reliability of the A-ADAS-Cog
was stable over time (r = 0.97). An evaluation of the construct validity of the A
ADAS-Cog using principal component analysis led to a solution with three factors
(memory, language and praxis), which explained 72% of the variance. The
concurrent validity of the A-ADAS-Cog was established using the A-MMSE score (r =
-0.86), CDR Sum of Boxes score (CDR-SB; r = 0.87), and global CDR score (CDR
Global; r = 0.74). Finally, the A-ADAS-Cog has an excellent discriminating power
in the diagnosis of AD (ROC area = 0.92). A cut-off score of 10 (sensitivity =
84% and specificity = 91%) is indicated for the screening of the AD. Overall, the
results indicated that the A-ADAS-Cog is psychometrically reliable and valid and
provides promising results for screening of dementia in Arabic speaking patients.
PMID- 28505979
TI - A Systematic Review and Meta-Analysis of Prevalence Studies of Sporadic Inclusion
Body Myositis.
AB - BACKGROUND: Sporadic Inclusion Body Myositis (sIBM) is a rare and slowly
progressive debilitating muscle disease with symptoms generally developing>=50
years of age. OBJECTIVE: To conduct a systematic review and meta-analysis of the
prevalence of sIBM literature, including a methodological quality assessment of
the selected papers. METHODS: A systematic search of Medline, Embase, Cochrane
Database of Systematic Reviews and major Myositis and Neurological conferences
was conducted. Articles reporting prevalence and published in English up to March
2017 were assessed for methodology quality using the Loney quality assessment,
Downs & Black score, and the Methodological Evaluation of Observational Research
checklists. Meta-analyses using random effects were completed on both general
population and>=50 years prevalence estimates. RESULTS: 315 articles were
retrieved and data were extracted from 10 relevant studies. One study was
subsequently excluded due to methodological issues. The meta-prevalence estimate
from 9 papers was 24.8/1,000,000 (95% CI: 20.0-29.6). The methodological quality
results were consistent across assessment tools with four articles scoring 4 or 5
out of 8 in the Loney assessment. The meta-prevalence of these four articles was
45.6/ 1,000,000 (95% CI: 35.9-55.2). CONCLUSION: There was high variability in
reported sIBM prevalence estimates and the quality of the studies conducted.
Existing evidence suggests an increase of prevalence estimates over time, which
may be explained by growing disease awareness, improvements in diagnostic
criteria and study methodologies. Further high quality studies are needed to
understand if prevalence varies across geographies or ethnicities.
PMID- 28505980
TI - Creation of a Novel Humanized Dystrophic Mouse Model of Duchenne Muscular
Dystrophy and Application of a CRISPR/Cas9 Gene Editing Therapy.
AB - Duchenne muscular dystrophy is caused by mutations in DMD which disrupt the
reading frame. Therapeutic strategies that restore DMD's reading frame, such as
exon skipping and CRISPR/Cas9, need to be tested in the context of the human DMD
sequence in vivo. We have developed a novel dystrophic mouse model by using
CRISPR/Cas9 to delete exon 45 in the human DMD gene in hDMD mice, which places
DMD out-of-frame. We have utilized this model to demonstrate that our clinically
relevant CRISPR/Cas9 platform, which targets deletion of human DMD exons 45-55,
can be directly applied in vivo to restore dystrophin.
PMID- 28505981
TI - Severe Exacerbation of Myasthenia Gravis Associated with Checkpoint Inhibitor
Immunotherapy.
AB - Monoclonal antibodies that target either PD-1 or PD-L1 have recently been
approved for treatment of advanced non-small cell lung cancer. These antibodies
are immune checkpoint inhibitors which have been shown to exacerbate Myasthenia
Gravis (MG) and other autoimmune diseases. While effective in preventing tumor
cells from evading immune attack, immune checkpoint inhibitors such as nivolumab,
an antibody directed against the programmed cell death protein-1 (PD-1) receptor
located on T-cells, may also cause immune dysregulation and could cause or
potentiate pre-existing autoimmune conditions. We present a patient with latent
ocular MG treated with nivolumab for her stage IV non-small cell lung cancer who
developed generalized MG and severe myasthenic crisis. Providers must be aware of
the risks inherent to these novel therapies since they can have life-threatening
effects.
PMID- 28505982
TI - Factors Contributing to Perceived Walking Difficulties in People with Parkinson's
Disease.
AB - BACKGROUND: While walking difficulties are common in people with Parkinson's
disease (PD), little is known about factors that independently contribute to
their perceived walking difficulties. OBJECTIVE: To identify factors that
independently contribute to perceived walking difficulties in people with PD.
METHODS: This study involved 243 (62% men) participants; their mean (min-max) age
and PD duration were 70 (45-93) and 8 (1-43) years, respectively. A postal survey
preceded a home visit that included observations, clinical tests, questions and
questionnaires that were administered as a structured interview. Perceived
walking difficulties (dependent variable) were assessed with the self
administered generic Walk-12 (Walk-12G, scored 0-42, higher = worse). Independent
variables included personal (e.g., age and general self-efficacy) and social
environmental factors (e.g., social support and living situation) as well as
disease-related factors including motor (e.g., freezing of gait (FOG) and
postural instability) and non-motor symptoms (e.g., fatigue and orthostatic
hypotension). Linear multiple regression analysis was used to identify factors
that independently contributed to perceived walking difficulties. RESULTS: Eight
significant independent variables explained 56.3% of the variance in perceived
walking difficulties. FOG was the strongest significant contributing factor to
perceived walking difficulties, followed by general self-efficacy, fatigue, PD
duration, lower extremity function, orthostatic hypotension, bradykinesia and
postural instability. CONCLUSION: Motor and non-motor symptoms as well as
personal factors (i.e., general self-efficacy) seem to be of importance for
perceived walking difficulties in PD. These findings might nurture future
interventions that address modifiable factors in order to enhance walking ability
in people with PD.
PMID- 28505984
TI - On a unique fellow and a good friend: Celebrating the life of Stefan Hesse and
his contributions to rehabilitation robotics, 1960-2016.
PMID- 28505983
TI - Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease: The Effect of
Varying Stimulation Parameters.
AB - Subthalamic Nucleus Deep Brain Stimulation (STN DBS) is a well-established and
effective treatment modality for selected patients with Parkinson's disease (PD).
Since its advent, systematic exploration of the effect of stimulation parameters
including the stimulation intensity, frequency, and pulse width have been carried
out to establish optimal therapeutic ranges. This review examines published data
on these stimulation parameters in terms of efficacy of treatment and adverse
effects. Altering stimulation intensity is the mainstay of titration in DBS
programming via alterations in voltage or current settings, and is characterised
by a lower efficacy threshold and a higher side effect threshold which define the
therapeutic window. In addition, much work has been done in exploring the effects
of frequency modulation, which may help patients with gait freezing and other
axial symptoms. However, there is a paucity of data on the use of ultra-short
pulse width settings which are now possible with technological advances. We also
discuss current evidence for the use of novel programming techniques including
directional and adaptive stimulation, and highlight areas for future research.
PMID- 28505985
TI - Upper limb robotics applied to neurorehabilitation: An overview of clinical
practice.
AB - BACKGROUND: During the last two decades, extensive interaction between clinicians
and engineers has led to the development of systems that stimulate neural
plasticity to optimize motor recovery after neurological lesions. This has
resulted in the expansion of the field of robotics for rehabilitation. Studies in
patients with stroke-related upper-limb paresis have shown that robotic
rehabilitation can improve motor capacity. However, few other applications have
been evaluated (e.g. tremor, peripheral nerve injuries or other neurological
diseases). PURPOSE: This paper presents an overview of the current use of upper
limb robotic systems for neurorehabilitation, and highlights the rationale behind
their use for the assessment and treatment of common neurological disorders.
CONCLUSIONS: Rehabilitation robots are little integrated in clinical practice,
except after stroke. Although few studies have been carried out to evaluate their
effectiveness, evidence from the neurosciences and indications from pilot studies
suggests that upper limb robotic rehabilitation can be applied safely in various
other neurological conditions. Rehabilitation robots provide an intensity,
quality and dose of treatment that exceeds therapist-mediated rehabilitation.
Moreover, the use of force fields, multi-sensory environments, feedback etc.
renders such rehabilitation engaging and motivating. Future studies should
evaluate the effectiveness of rehabilitation robots in neurological pathologies
other than stroke.
PMID- 28505987
TI - Improved grasp function with transcranial direct current stimulation in chronic
spinal cord injury.
AB - BACKGROUND: Recovering hand function has important implications for improving
independence of patients with tetraplegia after traumatic spinal cord injury
(SCI). Transcranial direct current stimulation (tDCS) is a noninvasive
neuromodulation technique that has potential to improve motor function.
OBJECTIVE: To investigate the effects of one session of 1 mA, 2 mA, and sham
anodal tDCS (a-tDCS) in the upper extremity (hand) motor performance (grasp and
lease) in patients with chronic cervical SCI. METHODS: Eleven participants with
incomplete SCI were randomized to receive 20 minutes of 1 mA, 2 mA, or sham
stimulation over the targeted motor cortex over three separated sessions. Hand
motor performance was measured by a hand robotic evaluation (kinematics) and the
Box and Blocks (BB) test before and after the stimulation period. RESULTS: A
significant improvement on the grasp mean to peak speed ratio (GMP) was observed
in the 2 mA group (pre: 0.38+/-0.02; post: 0.43+/-0.03; mean+/-SEM; p = 0.031).
There was no statistically significant difference in BB test results, however the
2 mA intervention showed a positive trend for improvement. CONCLUSIONS: A single
session of 2 mA of a-tDCS showed gains in hand motor function in patients with
chronic SCI that were not observed in functional clinical scales. The use of
robotic kinematics showed promising results in assessing small changes in motor
performance. Further studies are necessary to determine whether tDCS can be an
effective long-term rehabilitation strategy for individuals with SCI.
PMID- 28505986
TI - Combined transcranial direct current stimulation and robotic upper limb therapy
improves upper limb function in an adult with cerebral palsy.
AB - BACKGROUND: Robotic therapy can improve upper limb function in hemiparesis.
Excitatory transcranial direct current stimulation (tDCS) can prime brain motor
circuits before therapy. OBJECTIVE: We tested safety and efficacy of tDCS plus
robotic therapy in an adult with unilateral spastic cerebral palsy (USCP).
METHODS: In each of 36 sessions, anodal tDCS (2 mA, 20 min) was applied over the
motor map of the affected hand. Immediately after tDCS, the participant completed
robotic therapy, using the shoulder, elbow, and wrist (MIT Manus). The
participant sat in a padded chair with affected arm abducted, forearm supported,
and hand grasping the robot handle. The participant controlled the robot arm with
his affected arm to move a cursor from the center of a circle to each of eight
targets (960 movements). Motor function was tested before, after, and six months
after therapy with the Wolf Motor Function Test (WMFT) and Fugl-Meyer (FM).
RESULTS: Reaching accuracy on the robot task improved significantly after
therapy. The WMFT and FM improved clinically meaningful amounts after therapy.
The motor map of the affected hand expanded after therapy. Improvements were
maintained six months after therapy. CONCLUSIONS: Combined tDCS and robotics
safely improved upper limb function in an adult with USCP.
PMID- 28505988
TI - Intensive seated robotic training of the ankle in patients with chronic stroke
differentially improves gait.
AB - BACKGROUND: Robotic driven treatment plans targeting isolated joints of the upper
limb have improved the sensorimotor condition of patients with stroke. Similar
intensive efforts to allay lower limb gait impairment have not been so
successful. In patients with stroke, targeted robot assisted training of the
ankle joint, in a seated position, has demonstrated significant alterations in
ankle stiffness and foot-ankle orientation at foot strike which may provide a new
treatment option for gait impairment. OBJECTIVE: To determine if isolated robot
assisted training of the ankle joint improves chronic hemiparetic gait in
patients with stroke who are categorized according to baseline gait impairment.
METHODS: Patients with chronic stroke (>6mo) and hemiparetic gait (N = 29)
received 18 sessions of isolated robot-assisted motor training of the ankle
(3*/week for 6 weeks). All participants had stable clinical baseline scores
across three admission measures, and no participant was receiving simultaneous
outpatient rehabilitation. Baseline gait speed determined three impairment
groups: high, >0.8 m/s; medium, 0.4-0.8 m/s; low, <0.4 m/s. Outcome measures
included the Berg Balance Scale, the 6 Minute Walk Test, and the 10 Meter Walk
Test, and were recorded upon admission, discharge, and 3 months following
intervention. RESULTS: Three distinct and significant between-group patterns of
recovery emerged for gait speed. The within-group analysis showed that the medium
and high group exhibited significant improvements in gait speed and endurance
upon discharge, that were maintained at 3-months. Gait speed improvements were
clinically significant (>0.16 m/s) for the high function group across all gait
speed and endurance measures at discharge and at 3 months. The moderate group
also exhibited clinically significant improvements at follow-up on the 10 Meter
Walk Test, fast pace (0.16 m/sec), and approached clinical significance for the
10 Meter Walk comfortable pace (0.12 m/sec). The low group had small but
significant improvements, at discharge on two of the three gait measures, and
these improvements were maintained at 3 months. For balance measures, the low and
moderate impairment groups had significant improvements at discharge that were
robust on follow-up measure. The high function group demonstrated no significant
change in balance. CONCLUSIONS: Joint-specific robotic training of the paretic
ankle provided the most benefit to individuals with moderate or mild gait speed
impairments after stroke. Baseline gait speed function (low, moderate, high) was
associated with three distinct recovery profiles. This suggests that severity
specific intervention may be critical to improving efficiency of stroke recovery.
PMID- 28505989
TI - Pediatric robotic rehabilitation: Current knowledge and future trends in treating
children with sensorimotor impairments.
AB - BACKGROUND: Robot-aided sensorimotor therapy imposes highly repetitive tasks that
can translate to substantial improvement when patients remain cognitively engaged
into the clinical procedure, a goal that most children find hard to pursue.
Knowing that the child's brain is much more plastic than an adult's, it is
reasonable to expect that the clinical gains observed in the adult population
during the last two decades would be followed up by even greater gains in
children. Nonetheless, and despite the multitude of adult studies, in children we
are just getting started: There is scarcity of pediatric robotic rehabilitation
devices that are currently available and the number of clinical studies that
employ them is also very limited. PURPOSE: We have recently developed the MIT's
pedi-Anklebot, an adaptive habilitation robotic device that continuously
motivates physically impaired children to do their best by tracking the child's
performance and modifying their therapy accordingly. The robot's design is based
on a multitude of studies we conducted focusing on the ankle sensorimotor
control. In this paper, we briefly describe the device and the adaptive
environment we built around the impaired children, present the initial clinical
results and discuss how they could steer future trends in pediatric robotic
therapy. CONCLUSIONS: The results support the potential for future interventions
to account for the differences in the sensorimotor control of the targeted limbs
and their functional use (rhythmic vs. discrete movements and mechanical
impedance training) and explore how the new technological advancements such as
the augmented reality would employ new knowledge from neuroscience.
PMID- 28505990
TI - The features of Gait Exercise Assist Robot: Precise assist control and enriched
feedback.
AB - BACKGROUND: In a patient with severe hemiplegia, the risk of the knee giving way
is high during the early stage of gait exercise with an ankle-foot orthosis.
However, use of a knee-ankle-foot orthosis has many problems such as large amount
of assistance and compensatory motions. To resolve these problems, we have
engaged in the development of the Gait Exercise Assist Robot (GEAR). OBJECTIVE:
To evaluate the improvement efficiency of walk with GEAR in a stroke patient.
METHODS: The subject was a 70-year-old man presented with left thalamus
hemorrhage and right hemiplegia. The patient underwent exercise with the GEAR 5
days a week, for 40 minutes per day. We evaluated the Functional Independence
Measure score for walk (FIM-walk score) every week. The control group consisted
of 15 patients aged 20-75 years with hemiplegia after primary stroke, who had
equivalent walking ability with the subject at start. As the primary outcome, we
defined improvement efficiency of FIM-walk, which was gain of FIM-walk divided
the number of required weeks. RESULTS: Improvement efficiency of FIM-walk of the
subject was 1.5, while that of control group was 0.48+/-3.2 (mean+/-SD).
CONCLUSIONS: GEAR is potentially useful for gait exercise in hemiplegic patients.
PMID- 28505991
TI - Lower extremity robotic exoskeleton training: Case studies for complete spinal
cord injury walking.
AB - BACKGROUND: Recent advances in exoskeleton technology has made lower extremity
powered exoskeletons (LEPE) a viable treatment tool to restore upright walking
mobility to persons with spinal cord injury (SCI). OBJECTIVE: Evaluate ARKE
exoskeleton training within a rehabilitation centre environment. METHODS: Case
studies are presented for two male participants, age 41 and 30, motor complete
SCI at T6 (N01) and T12 (N02), respectively, as they progress from new LEPE users
to independent walking. The ARKE 2.0 LEPE (Bionik Laboratories Inc., Toronto,
Canada) was used for all training (hip and knee powered, forearm crutches,
control tablet). Data were collected on session times, activity metrics from ARKE
system logs, and qualitative questionnaire feedback. RESULTS AND CONCLUSION: N01
required 18, 30-minute training sessions to achieve independent walking. N01
walked independently within the 12 session target. Foot strikes were frequently
before the end of the programmed swing phase, which were handled by the ARKE
control system. Subjective ratings of LEPE learning, comfort, pain, fatigue, and
overall experience were high for sitting-standing and moderate to high for
walking. This reflected the complexity of learning to safely walk. Qualitative
feedback supported the continuation of LEPE use in rehabilitation settings based
on end-user desire for upright mobility.
PMID- 28505992
TI - The influence of a constraint and bimanual training program using a variety of
modalities on endurance and on the cardiac autonomic regulation system of
children with unilateral cerebral palsy: A self-control clinical trial.
AB - BACKGROUND: An intensive hybrid program, combining constraint with bimanual
training, improves upper extremity function as well as walking endurance of
children with unilateral cerebral palsy (UCP). Endurance improvement may be
associated with the cardiac autonomic regulation system (CARS) adaptation, known
to be impaired among these children. OBJECTIVE: To examine the influence of an
intensive hybrid program on CARS, walking endurance and the correlation with
upper extremity function of children with UCP. METHODS: Twenty-four children aged
6-10 years with UCP participated in a hybrid program, 10 days, 6 hours per day.
Data were collected pre-, post- and 3-months post-intervention. Main outcome
measures included the Polar RS800CX for heart rate (HR) and heart rate
variability (HRV) data, the 6-Minute Walk Test (6MWT) for endurance, and the
Assisting Hand Assessment (AHA) and Jebsen-Taylor Test of Hand Function (JTTHF)
for bimanual and unimanual function. RESULTS: A significant reduction in HR and
an increase in HRV at post- and 3-month post-intervention was noted (chi22= 8.3,
p = 0.016) along with a significant increase in 6MWT with a median increase of 81
meters (chi22= 11.0, p = 0.004) at the same interval. A significant improvement
was noted in unimanual and bimanual performance following the intervention.
CONCLUSIONS: An intensive hybrid program effectively improved CARS function as
well as walking endurance and upper extremity function in children with UCP
(213).
PMID- 28505993
TI - Inter-rater reliability of two-point discrimination in acute stroke patients.
AB - BACKGROUND: The two-point discrimination (2PD) test is widely used in clinical
practice to assess tactile acuity and central somatosensory function in stroke
patients. OBJECTIVES: The aim of this study was to evaluate the reliability of
2PD test in fingers on the affected and non-affected sides in acute stroke
patients. METHODS: This was a single group repeated-measures inter-rater
reliability study. Thirty adults with completed ischemic stroke and left paresis
participated in the study. Static 2PD sensation was assessed using a standardized
Dellon discriminator. Two examiners performed measurements of 2PD sensation on
both hands. Each examiner made three series of measurements at intervals of 1
minute. After 15 minutes, the study was conducted in the same order by a second
examiner. RESULTS: The ability for 2PD sensation was significantly reduced in all
examined fingers on the affected side in comparison to the non-affected side. The
difference was statistically significant (in each case, p < 0.0001). Inter-rater
reliability (ICC2,1) for the first measurement at the affected site ranged from
0.95 to 0.98; at the non-affected site ranged from 0.30 to 0.82. Analysis of the
average value of three measurements (ICC2,3) yielded values for the affected site
ranging from 0.98 to 0.99; at the non-affected site ranged from 0.81 to 0.95.
CONCLUSIONS: The 2PD sensation values for all fingers were higher for the
affected site in comparison to the non-affected site. Conducting three repeatable
measurements ensures measurement reliability and repeatability when evaluating
2PD sensation in fingers on both sides in acute stroke patients.
PMID- 28505994
TI - Effect of three-dimensional spine stabilization exercise on trunk muscle strength
and gait ability in chronic stroke patients: A randomized controlled trial.
AB - BACKGROUND: Three-dimensional spine stabilization exercise can strengthen the
trunk muscles with minimal spine movement. OBJECTIVE: To investigate the effects
of the newly developed Spine Balance three-dimensional (3D) system on trunk
strength and gait abilities of chronic stroke patients. METHODS: Twenty-four
chronic stroke patients were randomly assigned to an experimental (n = 12) or
control group (n = 12). The experimental and control groups performed spine
stabilization exercise by using the newly developed Spine Balance 3D system and
the well-known Bridge exercise thrice a week for 30 min per day for 7 weeks.
Timed up and go (TUG) test, 10-m walking test (10-m WT), trunk muscle strength,
and gait ability were evaluated before and after 7 weeks of intervention.
RESULTS: The 10-m WT, TUG, walking speed, non-affected side step length, and
distance in the experimental group, wherein trunk muscle strength was checked by
using the Spine Balance 3D system evaluation program, showed more significant
improvement than those in the control group (p < 0.05). CONCLUSION: We suggest
that the newly developed Spine Balance 3D system can be a more useful therapeutic
tool for rehabilitation of trunk muscle strength and gait abilities than bridge
exercise-based spine stabilization exercise in chronic stroke patients.
PMID- 28505995
TI - Prediction of post-stroke functional mobility from the initial assessment of
cognitive function.
AB - BACKGROUND: Cognitive impairment is frequently seen in patients with stroke. The
possible correlation between cognitive function and functional mobility has been
proposed; however, the prognostic importance of early cognitive function in
recovery of mobility has not been investigated in patients with stroke.
OBJECTIVE: The objective of this study is to investigate whether the cognitive
function in the acute phase can independently predict the recovery of mobility
after stroke, and to determine the cut-off value of each cognitive evaluation
test for community ambulation at six months. METHODS: Seventy two patients
underwent four domain-specific neuropsychological evaluation tests at about two
weeks after stroke; these included the word list memory test (WMT), construction
praxis test (CPT), verbal fluency test (VFT) and Boston naming test (BNT). The
Functional Ambulation Category (FAC) and ambulatory zone (AZ) at six months after
stroke were investigated as outcome variables. The domain-specific cognitive
function, along with other possible predictors for functional mobility, was
analyzed with regression analysis. RESULTS: The z-scores of WMT (p = 0.018) and
VFT (p = 0.012) were related to the independence in ambulation. The z-scores of
VFT (p = 0.006) and CPT (p = 0.009) were predictors for community ambulation,
with the cut-off values of -2.215 for VFT, and of -0.845 for CPT. CONCLUSIONS:
Cognitive impairment in the acute phase of stroke can be an independent
prognostic factor of functional mobility. Domain-specific neuropsychological
evaluation tests should be considered in the acute phase of stroke to predict the
recovery of functional mobility.
PMID- 28505996
TI - Depression one year after hemorrhagic stroke is associated with late worsening of
outcomes.
AB - BACKGROUND: Poststroke depression is the most common psychiatric sequelae of
stroke, and it's independently associated with increased morbidity and mortality.
Few studies have examined depression after intracranial hemorrhage (ICH).
OBJECTIVE: To investigate the relationship between depression, ICH and outcomes.
METHODS: A substudy of the prospective Diagnostic Accuracy of MRI in Spontaneous
Intracerebral Hemorrhage (DASH) study, we included 89 subjects assessed for
depression 1 year after hemorrhage. A Hamilton Depression Rating Scale score >10
defined depression. Univariate, multivariable, and trend analyses evaluated
relationships between depression, clinical, radiographic, and inflammatory
factors and modified Rankin score (mRS) at 90 days and one year. RESULTS:
Prevalence of depression at one year was 15%. Depression was not associated with
hematoma volumes, presence of IVH or admission NIHSS, nor with demographic
factors. Despite this, depressed patients had worse 1-year outcomes (p = 0.004)
and were less likely to improve between 3 and 12 months, and more likely to
worsen (p = 0.042). CONCLUSION: This is the first study to investigate depression
one year after ICH. Post-ICH depression was common and associated with late
worsening of disability unrelated to initial hemorrhage severity. Further
research is needed to understand whether depression is caused by worsened
disability, or whether the converse is true.
PMID- 28505997
TI - Characteristics of individuals seeking activity-based restorative therapy
following spinal cord injury: A focus on hope.
AB - BACKGROUND: There is a lack of evidence regarding the psychosocial
characteristics of individuals with spinal cord injury (SCI) undergoing activity
based restorative therapy (ABRT) treatment. OBJECTIVES: This study seeks to
describe the hopefulness of a sample of ABRT participants and describe the
relationship between hopefulness and level of rehabilitation engagement. METHODS:
A prospective cross-sectional cohort study was conducted using a convenience
sample of 73 individuals with SCI (mean time since injury = 66.6 months) seeking
out-patient, post-acute rehabilitation at a metropolitan ABRT center. Outcome
measures included a demographic survey, The Hope Scale, the Patient Health
Questionare-9 and the Hopkins Rehabilitation Engagement Rating Scale. RESULTS:
The ABRT group reported higher levels of hope (M = 54.78, SD = 7.13) than have
been reported in a sample of individuals with SCI seeking traditional
rehabilitation in the acute (M = 24.58, SD = 4.06) setting. Rehabilitation
engagement was not related to hopefulness in the ABRT group. CONCLUSIONS: The
ABRT group demonstrated high levels of hopefulness. The difference in hopefulness
noted between this group and previous studies could be due to the time elapsed
since injury, the presence of choice in the rehabilitation process, or the
possibility that individuals who chose to participate in ABRT may have inherently
different hopefulness characteristics than the broader SCI population.
PMID- 28505998
TI - "I really hope it comes back" - Olfactory impairment following traumatic brain
injury: A longitudinal study.
AB - BACKGROUND: Olfactory impairment (OI) can present in up to 66% of all individuals
following traumatic brain injury (TBI) and can have significant implications for
everyday life. OBJECTIVE: To investigate the predictive factors, natural
progression and consequences of OI following TBI in individuals 12 months post
injury. METHODS: In this prospective longitudinal study, 37 adults (28 males, 9
females), mean age 42.3 years (SD 19.4), with predominately severe TBI (mean
length of posttraumatic amnesia (PTA) 28.6 days, SD 22.6) were assessed using the
University of Pennsylvania Smell Identification Test (UPSIT). Each participant
also participated in an open ended interview to allow exploration of their
experience of having OI. RESULTS: Thirty (83.33%) of the participants
demonstrated persisting OI at 12 months. Nineteen of these participants
demonstrated no change in their OI severity category and 4 produced a poorer
performance. Thirteen participants (36.11%) demonstrated some recovery with 6 of
these performing within the 'normal' range for age andgender. CONCLUSIONS: OI is
an enduring impairment for a substantial proportion of individuals who experience
it following severe TBI. It impacts a range of everyday activities, regardless of
its severity, and requires comprehensive management during rehabilitation.
PMID- 28505999
TI - Efficacy of a combined therapeutic approach in the management of Pisa Syndrome.
AB - BACKGROUND: Pisa syndrome (PS) represents an important source of disability in
Parkinson's disease (PD). Currently no consensus has been reached on its
definition or diagnostic criteria, and therapeutic approaches are unspecific and
often futile. Recently the role of abdominal muscles, and in particular of the
external oblique (EO), in the pathogenesis of PS was hypothesized. OBJECTIVES: To
evaluate the role of EO and propose a combined therapeutic approach in the
management of PS. METHODS: Ten PD patients with PS underwent a combined protocol
based on repeated lidocaine injection in EO and rehabilitation program. RESULTS:
Our data confirm the primary role of EO muscles in PS pathogenesis and showed an
improvement in truncal flexion and balance with a positive impact on patients'
quality of life after treatment. CONCLUSIONS: These data highlight the need for
accurate characterization of PS focusing on the role of abdominal muscles and the
need for a specific rehabilitation protocol for PS management.
PMID- 28506000
TI - Therapeutic effects of oral dimethyl fumarate on stroke induced by middle
cerebral artery occlusion: An animal experimental study.
AB - BACKGROUND: Dimethyl fumarate (DMF) has immune-modulatory and neuro-protective
characteristics that can be used for treatment of acute ischemic stroke.
OBJECTIVE: To investigate the therapeutic effects of DMF on histological and
functional recovery of rats after transient middle cerebral artery (MCA)
occlusion. METHODS: 22 Sprague-Dawley male rats weighing 275-300 g were
randomized into three groups by block randomization. In the sham group (n = 7),
the neck was opened, but neither MCA was occluded, nor any drug was
administered.The control group (n = 7) was treated with vehicle (methocel) by
gavage for 14 days after MCA occlusion. In the DMF-treated group (n = 8),
treatment was performed with 15 mg/kg body weight dimethyl fumarate twice a day
for 14 days after MCA occlusion. Transient occlusion of the right MCA was
performed by intraluminal thread method in the DMF-treated and the control group.
Neurological deficit score (NDS), pole test, and adhesive removal test were
performed before the surgery, and on post-operative Days 0, 3, 5, 7, 10, and 14.
After the final behaviour test, the animals' brains were perfused and removed.
Brains were frozen and sectioned serially and coronally using a cryostat. Infract
volume and brain volume were estimated by stereology. RESULTS: The percentage of
infarct volume was significantly lower in DMF-treated animals (5.76%) than in the
control group (22.39%) (P < 0.0001). Regarding behavioural tests, the DMF-treated
group showed better function in NDS on Days 7 (P = 0.041) and 10 (P = 0.046), but
not in pole and adhesive removal tests. There was no significant correlation
between behavioural tests and histological results. CONCLUSION: Dimethyl fumarate
could be beneficial as a potential neuroprotective agent in the treatment of
stroke.
PMID- 28506001
TI - Motor cortex stimulation does not lead to functional recovery after experimental
cortical injury in rats.
AB - BACKGROUND: Motor impairments are among the major complications that develop
after cortical damage caused by either stroke or traumatic brain injury. Motor
cortex stimulation (MCS) can improve motor functions in animal models of stroke
by inducing neuroplasticity. OBJECTIVE: In the current study, the therapeutic
effect of chronic MCS was assessed in a rat model of severe cortical damage.
METHODS: A controlled cortical impact (CCI) was applied to the forelimb area of
the motor cortex followed by implantation of a flat electrode covering the
lesioned area. Forelimb function was assessed using the Montoya staircase test
and the cylinder test before and after a period of chronic MCS. Furthermore, the
effect of MCS on tissue metabolism and lesion size was measured using [18F]
fluorodesoxyglucose (FDG) MUPET scanning. RESULTS: CCI caused a considerable
lesion at the level of the motor cortex and dorsal striatum together with a long
lasting behavioral phenotype of forelimb impairment. However, MCS applied to the
CCI lesion did not lead to any improvement in limb functioning when compared to
non-stimulated control rats. Also, MCS neither changed lesion size nor
distribution of FDG. CONCLUSION: The use of MCS as a standalone treatment did not
improve motor impairments in a rat model of severe cortical damage using our
specific treatment modalities.
PMID- 28506002
TI - Transcranial direct current stimulation combined with visuo-motor training as
treatment for chronic stroke patients.
AB - BACKGROUND: Recent studies exploring the combined effect of motor learning and
transcranial direct current stimulation (tDCS) for stroke rehabilitation have
shown partially conflicting results. OBJECTIVE: To test the efficacy of an
optimized hand training approach combined with tDCS in stroke patients. METHODS:
In the present pilot study we investigated motor effects of four-week training
with a visuomotor grip force tracking task combined with tDCS in 11 chronic
stroke patients. Anodal (0.5 mA) or sham tDCS was applied over the primary motor
cortex of the lesioned side for 20 minutes, twice a day, during training.
RESULTS: No difference between the Active and Sham groups in the total upper
extremity (UE) Fugl-Meyer Assessment (FMA) score was found. The most prominent
recovery occurred in the shoulder-elbow FMA sub-score; in this segment a
significantly greater improvement in the Active compared to the Sham group was
observed up to two months after the intervention. Mean hold force during the
first treatment session predicted the change in the total UE FMA score after
treatment. CONCLUSION: Four-week visuo-motor training combined with tDCS showed
no difference between the Active and Sham groups in the total UE FMA score, which
may be explained by heterogeneity of the degree of recovery in the Active group.
However, the shoulder-elbow FMA sub-score improved significantly more in the
Active compared to the Sham group, which deserves further study.
PMID- 28506004
TI - Relationships between geometrical parameters and mechanical properties for a
helical braided flow diverter stent.
AB - BACKGROUND: Although flow diversion is a promising procedure for aneurysm
treatment, the safety and efficacy of this strategy have not been sufficiently
characterized. Both mechanical properties and flow reduction effects are
important factors in the design of an optimal stent. OBJECTIVE: We aimed to
clarify the contributions of strut size and pitch to the mechanical properties
(radial stiffness and longitudinal flexibility) and geometric characteristics
(porosity and pore density) related to flow reduction effects. METHODS: Crimping
and bending behaviors of the stents were simulated with the finite element
method. The relationships between the mechanical properties and geometric
characteristics were investigated by changing the strut size and pitch. RESULTS:
Within the porosity range of 79-82%, the radial stiffness of the stent was
similarly influenced by either the strut size or pitch. However, the longitudinal
flexibility tended to be influenced more by strut size than by pitch.
CONCLUSIONS: Adjusting the strut size rather than the pitch can change the
mechanical properties while minimizing the change in porosity or pore density
related to flow reduction effects.
PMID- 28506003
TI - Synergy effects of combined multichannel EMG-triggered electrical stimulation and
mirror therapy in subacute stroke patients with severe or very severe arm/hand
paresis.
AB - BACKGROUND: Neurorehabilitation requires the development of severity-dependent
and successful therapies for arm/hand rehabilitation in stroke patients.
OBJECTIVE: To evaluate the effectiveness of adding mirror therapy to bilateral
EMG-triggered multi-channel electrostimulation for the treatment of severe
arm/hand paresis in stroke patients. METHODS: The subjects of this randomized,
controlled, multicentre study were stroke patients who had suffered their first
insult between 1 and 6 months before study start and had severe or very severe
arm/hand paresis, as classified by Fugl-Meyer-Assessment. Subjects were randomly
allocated to an intervention group (n = 16) or control group (n = 17). Both
groups were treated for 3 weeks (5x week, 30 minutes) with bilateral EMG
triggered multi-channel electrostimulation. The intervention group additionally
received mirror feedback of the unaffected limb. The primary outcome measure was
motor recovery of the upper extremities, as measured by the Fugl-Meyer
Assessment. RESULTS: The Intervention Group with very severe paresis had
significantly better motor recovery in total Fugl-Meyer Assessment (p = 0.017) at
a medium effect size (Cohen) of d = 0.7, due to a significant recovery of
shoulder and elbow function (p = 0.003) in the Fugl-Meyer Assessment Part A
subtest. For subjects with severe paresis, additional mirror therapy did not
significantly influence outcome. CONCLUSION: Additional mirror therapy in
combination with EMG-triggered multi-channel electrostimulation is
therapeutically beneficial for post-acute stroke patients with very severe
arm/hand paresis.
PMID- 28506005
TI - Assessment of the dose distribution of Minibeam radiotherapy for lung tumors in
an anthropomorphic phantom: A feasibility study.
AB - BACKGROUND: Microbeam radiotherapy (MRT) is a treatment in which radiation field
is divided into several separate fields of 10-100 MUm width and 100-400 MUm
spacing. In this treatment, normal tissue can tolerate high doses that are
delivered to its small volumes. OBJECTIVE: MCNPX 2.4 Monte Carlo code was used to
calculate the dose distribution of MRT in a lung tumor in a simulated Rando
phantom. METHODS: The effects of tissue inhomogeneities, using contrast media and
changing the number of beams were investigated. Dose volume histograms and beam
profiles of target and organs at risk were assessed and the dose uniformity in
the target region was evaluated using homogeneity. The conformity indices also
used to quantify the conformation of the shape of prescribed isodose volume to
the shape and size of the target. RESULTS: Tissue inhomogeneity of this region
did not interfere significantly with target dose homogeneity. The use of contrast
media or increasing the number of beams improved target dose homogeneity and
decreased the dose to surrounding tissues. CONCLUSIONS: The results suggest that
further investigation and evaluation of MRT for treatment of chest tumors is
worthwhile.
PMID- 28506006
TI - Immediate responses to backpack carriage on postural angles in young adults: A
crossover randomized self-controlled study with repeated measures.
AB - BACKGROUND: Heavy backpacks have been associated with various postural changes
and consequently musculoskeletal disorders. OBJECTIVE: We evaluated the immediate
responses of varying backpack loads on cranio-vertebral angle (CVA), sagittal
shoulder angle (SSA) and trunk forward lean (TFL) of young adults between the
ages of 18-25 years. METHODS: This was a 3*3 cross over randomized controlled
study with repeated measures among a convenience sample of young adults (n = 30;
50% male, 50% female). Each participant in a standing posture was assessed at
four different loads: no backpack, carrying backpack of 5%, 10%, and 15% of body
weight (BW). A sagittal photograph was taken of the area of the body
corresponding to spinal angle during each of these test conditions to allow for
later analysis of postural deviations. Comparisons of the mean deviations of the
different postural angles from baseline and between test conditions were made
using ANOVA at p<=0.05. RESULTS: Generally, there was a trend toward a decrease
in the CVA and TFL with increasing backpack loads. Specifically, a significant
decrease was seen for TFL at10% and 15% BW loads when compared with no load
condition. In contrast, the decrease in CVA was only significant between no load
condition and 15% body weight load. The SSA remained unchanged with backpack
weight within 15% BW. CONCLUSION: Whereas the SSA of young adults may not be
upset by an acute loading with a backpack within 15% of body weight, a 15% BW
backpack led to more forward posture of the head on the neck. In addition,
backpack load as low as 10% BW is enough to cause an immediate forward lean of
the trunk.
PMID- 28506007
TI - Validation study of a Kinect based body imaging system.
AB - BACKGROUND: Understanding the reliability and precision of the data obtained
using three-dimensional body scanners is very important if it is intended to
replace the traditional data collection methods. If the collection of
anthropometric data with three-dimensional body scanners is a fast and reliable
process that produces precise data at a low price, it could be used for numerous
applications worldwide. Many studies have addressed data collected by white light
and laser based scanners. OBJECTIVE: This study provides a comparative analysis
between the anthropometric data collected using a Kinect body imaging system with
the data collected using traditional manual methods. Moreover, a comparison is
also made between the results obtained in this study and the results of previous
studies of different types of body scanners. METHODS: The Mean Absolute
Difference was calculated and all the values were compared to the maximum
allowable error defined in ISO 20685. Additionally, an analysis of the
significant differences between the two acquisition methods was also applied to a
physical mannequin, to understand how the body movement and body stance variation
in human participants impacts the results obtained. RESULTS: There are few body
measurements that are close to this restricted allowable error. The results were
better when the mannequin was measured. Although they were still above the ISO
20685 limit, they were much closer than the results obtained for human
participants. CONCLUSION: The main cause of the differences between the two
methods is the time required for the 3D system to acquire the data. The
involuntary body sway of human participants is more difficult to control when the
time span is too long.
PMID- 28506008
TI - Analysis of air temperature changes on blood pressure and heart rate and
performance of undergraduate students.
AB - BACKGROUND: The increase in air temperature has been associated with human
deaths, some of which are related to cardiovascular dysfunctions, and with the
reduction of physical and cognitive performance in humans. OBJECTIVE: To analyze
the relationship between blood pressure (BP) and heart rate (HR) and the
cognitive performance of students who were submitted to temperature changes in
classrooms. METHODS: The university students answered a survey that was adapted
from the Battery of Reasoning Tests over 3 consecutive days at different air
temperatures while their thermal state and HR were measured. During those 3 days,
BP and HR were evaluated before and after the cognitive test. RESULTS: The
average and final HR increased at high temperatures; the tests execution time was
reduced at high temperatures; and the cognitive tests was related to Mean BP at
the beginning of the test, the maximum HR during the test and the air
temperature. CONCLUSIONS: The cognitive performance of undergraduate students in
the field of engineering and technology will increase while performing activities
in a learning environment with an air temperature of approximately 23.3 degrees C
(according to their thermal perception), if students have an initial MBP of 93.33
mmHg and a 60 bpm HRmax.
PMID- 28506009
TI - Structural equation model of interactions between risk factors and work-related
musculoskeletal complaints among Iranian hospital nurses.
AB - BACKGROUND: Statistics indicate a high risk of developing work-related
musculoskeletal disorders among hospital nurses. The challenge is to understand
the associations between musculoskeletal symptoms and various individual and
occupational risk factors. OBJECTIVE: This study examined the direct and indirect
interactions of various risk factors with musculoskeletal complaints in hospital
nurses. METHOD: In a cross-sectional design, Iranian hospital nurses from Semnan
University of Medical Sciences participated in a questionnaire survey reporting
their perceived perceptions of various work-related risk factors and
musculoskeletal symptoms. We tested our proposed structural equation model to
evaluate the relations between latent and observed concepts and the relative
importance and strength of exogenous variables in explaining endogenous
musculoskeletal complaints. RESULTS: Measurement model fits the data relatively
acceptable. Our findings showed direct effects of psychological, role-related and
work posture stressors on musculoskeletal complaints. Fatigue mediated the
adverse indirect relations of psychological, role-related, work posture and
individual factors with musculoskeletal complaints. CONCLUSIONS: Structural
equation modeling may provide methodological opportunities in occupational health
research with a potential to explain the complexity of interactions among risk
factors. Prevention of work-related musculoskeletal disorders among nurses must
account for physical and psychosocial conditions.
PMID- 28506010
TI - Re-evaluation of a LEED Platinum Building: Occupant experiences of health and
comfort.
AB - BACKGROUND: There is a need to better understand the perceived experiences of
workers in green buildings as the literature to this point has been mixed.
OBJECTIVES: To re-evaluate occupant experiences within a LEED platinum building
and investigate current experiences in general. METHODS: An online post occupancy
evaluation (POE) survey of 62 occupants of LEED Platinum building on a US college
campus is reported. The online survey addressed indoor environmental quality in
relation to health, productivity and satisfaction. RESULTS: Of the respondents,
38.7% had participated in a prior POE of this building in 2011 and results were
compared for this subgroup, as well as for overall results. There was a
significant increase in satisfaction with office workstations and air freshness
as compared to 3 years earlier. However, there was also a significant increase in
reported frequency of all physical symptoms. When looking just at the current POE
results, control over features of the workstation had a significant relationship
with most outcomes of interest. CONCLUSION: While improvements have been noted,
issues continue to exist that have implications for health, productivity and
satisfaction. The results of this study have implications for the ergonomic
design of workstations and indoor environmental quality within LEED buildings.
PMID- 28506011
TI - Unemployment, life satisfaction and deprivation: Gender and partnership
differences in the context of economic recession.
AB - BACKGROUND: The economic recession produced a rapid rise of unemployment rates
that was more visible in Southern European countries. There is evidence that
unemployment correlates highly with individuals' poor life satisfaction.
OBJECTIVE: To analyse the relationship between life satisfaction, household
composition and socioeconomic deprivation in people facing unemployment during
the economic recession. METHODS: A sample of 748 unemployed people from Lisbon
(Portugal) completed a socio-demographic questionnaire, the Cantril's ladder of
life scale, and the latent and manifest benefits of work scale (LAMB). Multiple
regression analyses were used to test the associations between life satisfaction
and all other variables. RESULTS: Partnered people report higher life
satisfaction compared to singles. Financial deprivation and lack of structured
time were the strongest factors negatively related to life satisfaction in both
partnered and single people. Having children had a particular negative effect on
the life satisfaction of partnered men; and living with an unemployed partner
together with lack of social contact and high enforced activity had a negative
effect on life satisfaction in partnered women. CONCLUSION: The heterogeneity of
socioeconomic needs found by household composition bring practical policy
implications for support actions targeting unemployed individuals in the unique
context of economic recession.
PMID- 28506012
TI - I see so I feel: Coping with workplace violence among victims and witnesses.
AB - BACKGROUND: Workplace violence is a serious concern for workers' mental health
and well-being in high risk work sectors. OBJECTIVE: This study examined victims'
and witnesses' experiences after exposure to workplace violence, and the types of
help they used to cope with the violent event. METHODS: Workers (n = 211) from
five different work sectors participated in our study. Multiple mediation
analysis was used to investigate the indirect effects through psychological and
work consequences on victims' versus witnesses' differential likelihood of using
formal, paraformal and informal helping. RESULTS: Results showed that workplace
violence has detrimental effects on both victims and witnesses. Direct victims
were more negatively affected psychologically and at work than witnesses. The
indirect effect through psychological difficulty after experiencing workplace
violence was significant in predicting formal helping. The indirect effect
through reduced work functioning in predicting paraformal helping was also
significant. No significant indirect effect was found in predicting informal
helping. CONCLUSIONS: Both victims and witnesses used multiple types of helping
to cope with the violent event. This study has practical implications on
management and clinical practices for better organizations of resources in
helping victims and witnesses to cope with workplace violence.
PMID- 28506014
TI - Experiencing violence in a psychiatric setting: Generalized hypervigilance and
the influence of caring in the fear experienced.
AB - BACKGROUND: Exposure to violence in the mental health sector both affects
employees and has implications for the quality of care provided. OBJECTIVE: This
phenomenological study aims to describe and understand the ways in which acts of
aggression from a patient might affect workers in a psychiatric institute, their
relationships with the patients and the services offered. METHODS: Two semi
structured interviews were conducted with each of the 15 participants from
various professions within a psychiatric hospital. RESULTS: Our analysis reveals
four themes: hypervigilance, caring, specific fear toward the aggressor and
generalized fear of all patients. A state of hypervigilance is found among all
participants. An emphasis on caring is present among the majority and unfolds as
a continuum, ranging from being highly caring to showing little or no caring. A
feeling of fear is expressed and is influenced by the participant's place on the
caring continuum. Caring workers developed a specific fear of their aggressor,
whereas those showing little or no caring developed a generalized fear of all
patients. Following a violent event, caring participants maintained this outlook,
whereas those demonstrating little to no caring were more inclined to disinvest
from all patients. CONCLUSIONS: Hypervigilance and fear caused by experiences of
violence impact the quality of care provided. Considerable interest should thus
be paid to caring, which can influence fear and its effects.
PMID- 28506013
TI - The effects of physical training without equipment on pain perception and balance
in the elderly: A randomized controlled trial.
AB - BACKGROUND: Research supports a link between exercise and falls prevention in the
older population. OBJECTIVES: Our aims were to evaluate pain perception and
balance skills in a group of elderly subjects and to examine the consequences of
a standardized equipment-free exercise program intervention on these variables.
The study utilized a randomized controlled trial method. METHODS: 92 subjects
were recruited from a rural Sicilian village (Resuttano, Sicily, Italy). Subjects
were randomly split into two groups, an experimental group (EG; n = 49) and a
control group (CG; n = 43). Qualified fitness instructors delivered the
standardized physical exercise program for the EG whilst the CG did not receive
this exercise intervention. The Berg Balance Scale and the Oswestry Disability
Index were administered in both groups before (T0) and after the intervention
(T1). RESULTS: At T1, the EG group significantly improvement in balance (p <
0.0001) and pain perception (p < 0.0001). No significant differences were found
within the CG both in BBS and ODI, respectively. CONCLUSIONS: Our findings
suggest that a 13-weeks standardized exercise equipment-free program is effective
in improving balance and perception of pain in the elderly. This type of
intervention can consequently provide a low cost strategy to counteract the rate
of disability in elderly.
PMID- 28506015
TI - Review on pen-and-paper-based observational methods for assessing ergonomic risk
factors of computer work.
AB - BACKGROUND: Computer works are associated with Musculoskeletal Disorders (MSDs).
There are several methods have been developed to assess computer work risk factor
related to MSDs. OBJECTIVE: This review aims to give an overview of current
techniques available for pen-and-paper-based observational methods in assessing
ergonomic risk factors of computer work. METHODS: We searched an electronic
database for materials from 1992 until 2015. The selected methods were focused on
computer work, pen-and-paper observational methods, office risk factors and
musculoskeletal disorders. This review was developed to assess the risk factors,
reliability and validity of pen-and-paper observational method associated with
computer work. Two evaluators independently carried out this review. RESULTS:
Seven observational methods used to assess exposure to office risk factor for
work-related musculoskeletal disorders were identified. The risk factors involved
in current techniques of pen and paper based observational tools were postures,
office components, force and repetition. From the seven methods, only five
methods had been tested for reliability. They were proven to be reliable and were
rated as moderate to good. For the validity testing, from seven methods only four
methods were tested and the results are moderate. CONCLUSION: Many observational
tools already exist, but no single tool appears to cover all of the risk factors
including working posture, office component, force, repetition and office
environment at office workstations and computer work. Although the most important
factor in developing tool is proper validation of exposure assessment techniques,
the existing observational method did not test reliability and validity.
Futhermore, this review could provide the researchers with ways on how to improve
the pen-and-paper-based observational method for assessing ergonomic risk factors
of computer work.
PMID- 28506016
TI - Comparison of the strength endurance parameters for the Baltimore Therapeutic
Equipment (BTE) Simulator II and the Jamar Handgrip Dynamometer.
AB - BACKGROUND: The purpose of this study was to provide evidence regarding the
Baltimore Therapeutic Equipment (BTE) Work Simulator II's recommended grip
endurance protocol. The grip endurance protocol of the BTE Simulator II has never
been validated, though it has been used often for the rehabilitation of work
related injuries and other occupational dysfunctions. Without validation, the
grip endurance protocol may or may not be providing skilled clinicians with
appropriate evaluation results. This study evaluated a protocol comparing the BTE
Simulator II to the Jamar Dynamometer to determine how the BTE compares to the
Jamar device. OBJECTIVE: To establish whether the recommended grip endurance
protocol for the BTE Simulator II is comparable to the parameters established for
the Jamar handgrip dynamometer. METHODS: Data were gathered from 140 participants
ages 18 to 40 at the time of the study. Participants completed protocols
established for the BTE Simulator II and compared to a performance of a grip
strength endurance protocol for the Jamar Handgrip Dynamometer. After
establishing baseline strength levels for the participants, they were timed to
see how long they could sustain a 30% maximum voluntary contraction (MVC) on each
device. Sample t-tests were calculated to compare the results of the BTE
Simulator II to the previously validated Jamar device. RESULTS: A dependent
sample t-test found no statistically significant difference between the times a
participant sustained 30% of their maximum voluntary contraction (MVC) on the BTE
Simulator II with attachment #162 versus the Jamar Dynamometer when comparing the
differences of the means. This provides possible evidence of validity for the BTE
endurance protocol. The independent sample t-test found no statistically
significant difference between the grip endurance of the males versus the
females, however, the means indicate men sustained 30% of their MVC longer than
their female counterparts on the BTE. CONCLUSIONS: The findings indicate that the
30% MVC may be a reliable baseline for grip strength endurance testing following
the BTE Simulator II protocol. This suggests that the BTE Simulator II's
endurance protocol may be a useful tool to document client progression during
rehabilitation after sustaining an upper extremity dysfunction. Further research
is needed to validate this protocol using different populations.
PMID- 28506017
TI - Prevalence of serious psychological distress among slaughterhouse workers at a
United States beef packing plant.
AB - BACKGROUND: Workers in the animal slaughter and processing industry in the United
States experience high rates of occupational injury as well as stressful work
conditions, yet mental health in this workforce remains largely unstudied.
OBJECTIVE: To assess prevalence of serious psychological distress (SPD) in a
sample of industrial US slaughterhouse workers. PARTICIPANTS: Workers at an
industrial beef packing plant in Nebraska, United States (n = 137). METHODS: We
interviewed workers using the Kessler-6, a well-validated measure of non-specific
anxiety disorders, to assess SPD. We compared SPD prevalence with national
estimates from 2009 CDC's Behavioral Risk Factor Surveillance Study. RESULTS:
Prevalence of SPD among workers was 4.4%, compared to United States population
wide prevalence of 3.6%. Prevalence of mild and moderate psychological distress
among these workers (14.6%) was also higher than national estimates. Recent
occupational injury, work area and job activities were not associated with
elevated prevalence of SPD. Non-Hispanic white workers experienced elevated
prevalence of SPD compared to Hispanic or Latino workers (prevalence odds ratio:
6.4; CI: 1.3, 30.5; p = 0.012). CONCLUSION: Workers at a US industrial
slaughterhouse experienced higher prevalence of SPD compared to United States
population-wide estimates, but occupational risk factors for this outcome were
not identified.
PMID- 28506018
TI - Return to work predictors of stroke survivors and their spousal caregivers.
AB - BACKGROUND: Return to work is an issue of concern for stroke survivors and their
spouses. Ramifications may include loss of income and self-efficacy. OBJECTIVE:
This study describes the return to work patterns of stroke survivors and their
spousal caregivers post stroke. METHODS: One hundred fifty-nine dyads were
examined for their return to work patterns at baseline (post hospital discharge)
and then at 3 month intervals for one year. Relationships were determined between
work and gender, age, ethnicity, education, type of insurance, type of stroke,
location of stroke, motor and cognitive functional status, depression, mutuality,
and life satisfaction. RESULTS: Low levels of return to work by stroke survivors
(7.5%) and a small decrease in the amount of working caregivers (from 45.3% to
40.35%) were found one year post baseline. Variables that predicted return to
work changed over the five data points except for younger age for the caregiver,
which was consistently significant across all data points. Three case scenarios
representative of working patterns are offered. CONCLUSIONS: Further research is
needed regarding the return to work needs of stroke survivors and their spousal
caregivers, particularly what role the occupational therapist may play in
facilitating that process.
PMID- 28506020
TI - Rigid motion artifact reduction in CT using frequency domain analysis.
AB - BACKGROUND: It is often unrealistic to assume that the subject remains stationary
during a computed tomography (CT) imaging scan. A patient rigid motion can be
decomposed into a translation and a rotation around an origin. How to minimize
the motion impact on image quality is important. OBJECTIVE: To eliminate
artifacts caused by patient rigid motion during a CT scan, this study
investigated a new method based on frequency domain analysis to estimate and
compensate motion impact. METHODS: Motion parameters was first determined by the
magnitude correlation of projections in frequency domain. Then, the estimated
parameters were applied to compensate for the motion effects in the
reconstruction process. Finally, this method was extended to helical CT. RESULTS:
In fan-beam CT experiments, the simulation results showed that the proposed
method was more accurate and faster on the performance of motion estimation than
using Helgason-Ludwig consistency condition method (HLCC). Furthermore, the
reconstructed images on both simulated and human head experiments indicated that
the proposed method yielded superior results in artifact reduction. CONCLUSIONS:
The proposed method is a new tool for patient motion compensation, with a
potential for practical application. It is not only applicable to motion
correction in fan-beam CT imaging, but also to helical CT.
PMID- 28506021
TI - Metal artifact reduction in spiral fan-beam CT using a new sinogram segmentation
scheme.
AB - Objective of this study is to present and test a new method for metal artifact
reduction (MAR) by segmenting raw CT data (sinogram). The artifact suppression
technique incorporates two steps namely, metal projection segmentation in the
sinogram and replacement of segmented regions by new values using an
interpolation method. The proposed segmentation algorithm uses the sinogram
instead of reconstructed CT slices. First, one of the best and newest region
based geometric active contour models is used to detect projection data affected
by metal objects (missing projections). Then, the Hough-transform method is
applied to detect all sinusoidal-like curves belonging to metal objects. Finally,
a post image processing technique is used aiming to increase accuracy of the
segmentation process. To provide a proof of performance, CT data of two patients
with metallic teeth filling and pelvis prosthesis were included in the study as
well as CT data of a phantom with metallic teeth inserts. Accuracy was determined
by comparing mean, variance, mean squared error (MSE) and, peak signal to noise
ratio (PSNR) as evaluation measurements of distortion in phantom images with
respect to metallic teeth (original and suppressed) and without metallic teeth
inserts. Quantitative results showed an average improvement of 12 dB in terms of
PSNR and 517 in terms of MSE when the new MAR method was applied to remove metal
artifacts. Qualitative improvement was also assessed by comparing uncorrected
clinical images with artifact suppressed images. Moreover, qualitative comparison
of the results of the proposed new method with the existing methods of MAR showed
the superiority of the new method tested in this study.
PMID- 28506022
TI - Breast osteoblastoma and recurrence after resection: Demonstration by color
Doppler ultrasound.
AB - Osteoblastoma is a rare benign primary bone tumor, which occurs in any part of
the skeleton. Extraskeletal osteoblastoma is rather rare. We presented an
extremely rare case of extraskeletal osteoblastoma located in the breast. The
tumor recurred 7 months later after resection and transformed to aggressive
osteoblastoma. The histopathological features, ultrasonic manifestations and
ultrasonic differential diagnoses of the primary and recurrent tumors were
discussed. The recommended treatment of the tumor is surgical excision. Due to
its tendency of recurrence and potential malignant transformation, adequate
resection and careful follow up is essential.
PMID- 28506023
TI - Optimization method of MRI scan parameters of a double inversion recovery
sequence using a T1 map and a developed analysis algorithm.
AB - BACKGROUND: Optimizing scan parameters for double inversion recovery (DIR)
sequences remains difficult. OBJECTIVE: To evaluate a new method for optimizing
DIR sequence scan parameters using T1 mapping and a newly developed analysis
algorithm. METHODS: Twelve healthy volunteers underwent T1 mapping and DIR
magnetic resonance imaging. The following steps were used for image optimization
including: 1) measurement of gray matter (GM), white matter (WM), and
cerebrospinal fluid (CSF) T1 values to create a T1 map; 2) calculation of
optimized scan parameters by using a developed analysis algorithm; 3) performance
assessment of DIR magnetic resonance imaging by using the calculated optimized
imaging parameters. Additionally, we used scan parameters from previous studies
to obtain DIR images in order to evaluate our new method. The contrast between GM
and suppressed tissues was compared between these images and those obtained using
the optimized parameters. RESULTS: Using our optimization method, WM and CSF
regions were suppressed uniformly for all scan conditions. The contrast was
significantly higher in images obtained using this optimization method compared
to those obtained using previously published parameters (p < 0.01). CONCLUSIONS:
It is possible to obtain superior DIR images by using an optimization method that
involves T1 mapping and a newly developed analysis algorithm.
PMID- 28506024
TI - MicroRNA expression profiling in endometriosis-associated infertility and its
relationship with endometrial receptivity evaluated by ultrasound.
AB - OBJECTIVE: To investigate the microRNA expression profiling in endometriosis
associate infertility, and relationship between the microRNA expression and
endometrial receptivity evaluated by ultrasound. METHODS: First, miRNA expression
profiling difference of ectopic endometrium between 8 endometriosis patients and
6 endometriosis-free patients were compared. Bioinformatics analyses detected 61
differentially expressed (DE) known miRNAs and 57 DE novel miRNAs. Next, other 24
patients were selected for checking the microRNAs in differential expression by
RT-PCR. Among them, case and control groups include 14 endometriosis and 10
endometriosis-free infertility patients, respectively. Last, endometrial
receptivity of other 20 endometriosis patients was evaluated by ultrasound. In
this group of patients, 12 had high endometrial receptivity, in which infertility
is caused by fallopian tube occlusion, and 8 had low endometrial receptivity. The
study compared endometrial miRNAs expression between two groups, and also
evaluated the relationship between the endometrial miRNAs expression and the
endometrial receptivity. RESULTS: First, study indicated that "proteinaceous
extracellular matrix," "laminin binding" and "extracellular matrix binding" were
enriched in 6 up-regulated miRNA targets, while "cell proliferation" was enriched
in the 4 down-regulated miRNA targets. Second, 10 miRNAs in different expression
(miR-1304- 3p, miR-544b, miR-3684, miR-494-5p, miR-4683, miR-6747-3p; miR-3935,
miR-4427, miR-652-5p, miR-205-5p) were detected by RT-PCR, and the results showed
statistically significant differences between 2 groups in all 10 miRNAs. Third,
the expression levels of miR-1304-3p, miR-494-5p, and miR-4427 were different
between the two groups with different endometrial receptivity. But for the miR
544b, there was no statistically significant difference between two groups.
CONCLUSIONS: The study provided a comprehensive understanding to the current
knowledge in the field of miRNAs in endometriosis and the relationship between
them and the endometrial receptivity. miRNAs could be used as diagnostic
biomarkers and therapeutic agents for this disease. The combination of ultrasound
and miRNAs detection could be a better choice for the diagnosis of infertility in
the future.
PMID- 28506025
TI - Modified Pechini Processing of Barium and Lanthanum-Lithium Titanate
Nanoparticles and Thin Films.
AB - Barium-strontium titanate (BST) Ba0.6Sr 0.4 TiO3 and lanthanum-lithium titanate
(LLT) La0.5Li0.5TiO3 nanopowders and thin films have been obtained via the
modified Pechini route. Polyesterification and complexation processes of gel
formation have been examined. Hypothetical models of coordinative polymers formed
in sol-gel system have been suggested. It has been shown that BST and LLT solid
solutions form in one step at relatively low temperature. X-ray diffraction
confirms that the final products, which are single phases and have cubic shape,
are formed at 600 and 700 degrees C for BST and LLT respectively. It has been
found that use of thermal shock as pretreatment allows to increase the density of
BST- and LLT-based thin films.
PMID- 28506026
TI - Raman Submicron Spatial Mapping of Individual Mn-doped ZnO Nanorods.
AB - ZnO nanorods (NRs) arrays doped with a large concentration of Mn synthesized by
aqueous chemical growth and were characterized by SEM, photoluminescence, Raman
scattering, magnetic force microscopy (MFM). By comparison of spectra taken on
pure and Mn-doped ZnO NRs, a few new Raman impurity-related phonon modes,
resulting from the presence of Mn in the investigated samples. We also present a
vibrational and magnetic characterization of individual lying nanorods using
Raman and MFM imaging. Confocal scanning micro-Raman mapping of the spatial
distribution of intensity and frequency of phonon modes in single Mn-doped ZnO
NRs nanorods is presented and analyzed for the first time. Mn-related local
vibrational modes are also registered in Raman spectra of the single nanorod,
confirming the incorporation of Mn into the ZnO host matrix. At higher Mn
concentration the structural transformation toward the spinel phase ZnMn2O4 and
Mn3O4 is observed mainly in 2D bottom layers. MFM images of Mn-doped ZnO NR
arrays and single nanorod were studied in nanoscale at room temperature and
demonstrate magnetic behavior. The circular domain magnetic pattern on top of
single nanorod originated to superposition of some separate domains inside rod.
This demonstrates that long-range ferromagnetic order is present at room
temperature. Aligned Mn-doped ZnO NRs demonstrates that long-range ferromagnetic
order and may be applied to future spintronic applications.
PMID- 28506027
TI - Final Report of Unmet Needs of Interferon-Based Therapy for Chronic Hepatitis C
in Korea: Basis for Moving into the Direct-Acting Antiviral Era.
AB - Background/Aims: To evaluate the era of direct acting antivirals (DAAs), we must
understand the treatment patterns and outcomes of interferon-based therapy for
hepatitis C virus (HCV) infection. We aimed to elucidate the treatment rate,
factors affecting treatment decisions, and efficacy of interferon- based therapy
in a real-world setting. Methods: This nationwide cohort study included 1,191
newly diagnosed patients with chronic HCV infection at seven tertiary hospitals
in South Korea. Subjects were followed retrospectively until March 2015, which
was just before the approval of DAA therapy. Results: In total, 48.2% and 49.3%
of the patients had HCV genotypes 1 and 2, respectively. Interferon-based therapy
was initiated in 541 patients (45.4%). The major reasons for no treatment
included ineligibility (18.9%), concern about adverse events (22.3%), cost
(21.5%), and an age >75 years (19.5%). Interferon-based therapy was discontinued
(18.5%) mainly due to adverse events (n=66). The intent-to-treat analysis found
that the sustained virologic response (SVR) rate was 58.3% in genotype 1 patients
and 74.7% in nongenotype 1 patients. Conclusions: Approximately one-third of
newly diagnosed HCV patients in South Korea received interferon-based therapy and
showed a suboptimal SVR rate. Diagnosis of patients at younger ages and with a
less advanced liver status and reducing the DAA therapy cost may fulfill unmet
needs.
PMID- 28506029
TI - Establishment of a Disease-Specific Graded Prognostic Assessment for
Hepatocellular Carcinoma Patients with Spinal Metastasis.
AB - Background/Aims: Hepatocellular carcinoma (HCC) patients with spinal metastasis
(SM) show heterogeneous lengths of survival. In this study, we develop and
propose a graded prognostic assessment for HCC patients with SM (HCC-SM GPA).
Methods: We previously reported the outcomes of 192 HCC patients with SM who
received radiotherapy from April 1992 to February 2012. Prognostic factors that
significantly affected survival in that study were used to establish the HCC-SM
GPA. Validation was performed using an independent cohort of 63 patients
recruited from September 2011 to March 2016. Results: We developed the HCC-SM GPA
using the following factors: Eastern Cooperative Oncology Group performance
status (0-2, 0 point; 3-4, 1 point), controlled primary HCC (yes, 0 point; no, 2
points), and extrahepatic metastases other than bone (no, 0 point; yes, 1 point).
Patients were stratified into low (GPA=0), intermediate (GPA=1 to 2), and high
risk (GPA=3 to 4). When applied to the validation cohort, the HCC-SM GPA
determined median survival durations of 13.6, 4.8, and 2.6 months and 1-year
overall survival rates of 58.3%, 17.8%, and 7.3% for the low-, intermediate-, and
high-risk patient groups, respectively (p<0.001). Conclusions: Our newly proposed
HCC-SM GPA successfully predicted survival outcomes.
PMID- 28506028
TI - Comparison of the Hospital-Acquired Clostridium difficile Infection Risk of Using
Proton Pump Inhibitors versus Histamine-2 Receptor Antagonists for Prophylaxis
and Treatment of Stress Ulcers: A Systematic Review and Meta-Analysis.
AB - Background/Aims: Although proton pump inhibitors (PPIs) have been widely used for
the prevention and treatment of stress gastric ulcers in hospital settings, there
are concerns that PPIs increase the risk of Clostridium difficile infection
(CDI). However, little is known about the risk of CDI following PPI and histamine
2 receptor antagonist (H2RA) use. We evaluated the comparative hospital-acquired
CDI occurrence risk associated with the concurrent use of PPIs versus H2RAs.
Methods: A systematic search of PubMed, MEDLINE/Ovid, Cumulative Index to Nursing
and Allied Health Literature (CINAHL), Web of Science, and Google Scholar through
August 19, 2016, identified 12 studies that reported the hospital-acquired CDI
occurrence following H2RA and PPI use for the prevention and treatment of stress
gastric ulcers. Random-effects pooled odds ratios and 95% confidence intervals
were estimated. Heterogeneity was measured using I2, and a meta-regression
analysis was conducted. The Grading of Recommendations Assessment, Development,
and Evaluation (GRADE) system was used to assess the overall quality of the
evidence. Results: A total of 74,132 patients from 12 observational studies were
analyzed. Compared to H2RAs, PPIs increased the risk of CDI by 38.6% (pooled odds
ratio, 1.386; 95% confidence interval, 1.152 to 1.668; p=0.001; I2=42.81%).
Subgroup analyses of the purpose of study medication use, study site, and study
design confirmed the consistency of a greater CDI risk with PPIs than with H2RAs.
The overall quality of evidence was rated as low. Conclusions: The use of PPIs
for both the prevention and treatment of stress ulcers was associated with a
38.6% increased risk of hospital-acquired CDI occurrence compared to H2RA use.
PMID- 28506031
TI - Identification and Characterization of Protein Arginine Methyltransferase 1 in
Acanthamoeba castellanii.
AB - Protein arginine methyltransferase (PRMT) is an important epigenetic regulator in
eukaryotic cells. During encystation, an essential process for Acanthamoeba
survival, the expression of a lot of genes involved in the encystation process
has to be regulated in order to be induced or inhibited. However, the regulation
mechanism of these genes is yet unknown. In this study, the full-length 1,059 bp
cDNA sequence of Acanthamoeba castellanii PRMT1 (AcPRMT1) was cloned for the
first time. The AcPRMT1 protein comprised of 352 amino acids with a SAM-dependent
methyltransferase PRMT-type domain. The expression level of AcPRMT1 was highly
increased during encystation of A. castellanii. The EGFP-AcPRMT1 fusion protein
was distributed over the cytoplasm, but it was mainly localized in the nucleus of
Acanthamoeba. Knock down of AcPRMT1 by synthetic siRNA with a complementary
sequence failed to form mature cysts. These findings suggested that AcPRMT1 plays
a critical role in the regulation of encystation of A. castellanii. The target
gene of AcPRMT1 regulation and the detailed mechanisms need to be investigated by
further studies.
PMID- 28506030
TI - Simeprevir-Based Triple Therapy with Reduced Doses of Pegylated Interferon alpha
2a Plus Ribavirin for Interferon Ineligible Patients with Genotype 1b Hepatitis C
Virus.
AB - Background/Aims: The present study aimed to evaluate the safety and efficacy of
simeprevir-based triple therapy with reduced doses of pegylated interferon (PEG
IFN) and ribavirin for interferon (IFN) ineligible patients, such as elderly
and/or cirrhotic patients, and to elucidate the factors contributing to a
sustained virologic response (SVR). Methods: One hundred IFN ineligible patients
infected with genotype 1b hepatitis C virus (HCV) were treated. Simeprevir (100
mg) was given orally together with reduced doses of PEG-IFN-alpha 2a (90 MUg),
and ribavirin (200 mg less than the recommended dose). Results: The patients'
median age was 70 years, and 70 patients were cirrhotic. Three patients (3%)
discontinued treatment due to adverse events. The SVR rate was 64%. Factors that
significantly contributed to the SVR included the gamma-glutamyl transferase and
alpha-fetoprotein levels, interleukin- 28B (IL28B) polymorphism status, and the
level and reduction of HCV RNA at weeks 2 and 4. The multivariate analysis showed
that the IL28B polymorphism status was the only independent factor that predicted
the SVR, with a positive predictive value of 77%. Conclusions: Simeprevir-based
triple therapy with reduced doses of PEG-IFN and ribavirin was safe and effective
for IFN ineligible patients infected with genotype 1b HCV. IL28B polymorphism
status was a useful predictor of the SVR.
PMID- 28506032
TI - DNA Methylation of Gene Expression in Acanthamoeba castellanii Encystation.
AB - Encystation mediating cyst specific cysteine proteinase (CSCP) of Acanthamoeba
castellanii is expressed remarkably during encystation. However, the molecular
mechanism involved in the regulation of CSCP gene expression remains unclear. In
this study, we focused on epigenetic regulation of gene expression during
encystation of Acanthamoeba. To evaluate methylation as a potential mechanism
involved in the regulation of CSCP expression, we first investigated the
correlation between promoter methylation status of CSCP gene and its expression.
A 2,878 bp of promoter sequence of CSCP gene was amplified by PCR. Three CpG
islands (island 1-3) were detected in this sequence using bioinformatics tools.
Methylation of CpG island in trophozoites and cysts was measured by bisulfite
sequence PCR. CSCP promoter methylation of CpG island 1 (1,633 bp) was found in
8.2% of trophozoites and 7.3% of cysts. Methylation of CpG island 2 (625 bp) was
observed in 4.2% of trophozoites and 5.8% of cysts. Methylation of CpG island 3
(367 bp) in trophozoites and cysts was both 3.6%. These results suggest that DNA
methylation system is present in CSCP gene expression of Acanthamoeba. In
addition, the expression of encystation mediating CSCP is correlated with
promoter CpG island 1 hypomethylation.
PMID- 28506033
TI - Differential Protein Expressions in Virus-Infected and Uninfected Trichomonas
vaginalis.
AB - Protozoan viruses may influence the function and pathogenicity of the protozoa.
Trichomonas vaginalis is a parasitic protozoan that could contain a double
stranded RNA (dsRNA) virus, T. vaginalis virus (TVV). However, there are few
reports on the properties of the virus. To further determine variations in
protein expression of T. vaginalis, we detected 2 strains of T. vaginalis; the
virus-infected (V+) and uninfected (V-) isolates to examine differentially
expressed proteins upon TVV infection. Using a stable isotope N-terminal labeling
strategy (iTRAQ) on soluble fractions to analyze proteomes, we identified 293
proteins, of which 50 were altered in V+ compared with V- isolates. The results
showed that the expression of 29 proteins was increased, and 21 proteins
decreased in V+ isolates. These differentially expressed proteins can be
classified into 4 categories: ribosomal proteins, metabolic enzymes, heat shock
proteins, and putative uncharacterized proteins. Quantitative PCR was used to
detect 4 metabolic processes proteins: glycogen phosphorylase, malate
dehydrogenase, triosephosphate isomerase, and glucose-6-phosphate isomerase,
which were differentially expressed in V+ and V- isolates. Our findings suggest
that mRNA levels of these genes were consistent with protein expression levels.
This study was the first which analyzed protein expression variations upon TVV
infection. These observations will provide a basis for future studies concerning
the possible roles of these proteins in host-parasite interactions.
PMID- 28506034
TI - Occurrence of Cryptosporidium and Giardia and the Relationship between Protozoa
and Water Quality Indicators in Swimming Pools.
AB - A total of 60 samples were collected from 35 swimming pools in Beijing, China,
and the presence of Cryptosporidium and Giardia were investigated. The results
showed that 16.7% and 15.0% of samples were positive for Cryptosporidium oocyst
and Giardia cysts, respectively, with a mean concentration of 0.30 oocysts/10 L
and 0.27 cysts/10 L. The oocysts and cysts were found to have higher rates of
occurrence in August than in May. Genotyping confirmed the presence of
Cryptosporidium hominis, C. parvum, and Giardia assemblages A and B, all of which
were associated with human infections. The predominant species/assemblages were
C. hominis and Giardia assemblage A. Analyses of the relationships between
parasite oocysts/cysts, indicator bacteria, and physical-chemical parameters
revealed that there was no correlation between 2 parasites and fecal bacterial
indicators, whilst there was a significant correlation between protozoa and urea
concentration, which indicates that urea concentration rather than fecal
bacterial indicators might be an appropriate index for chlorine-resistant
protozoa in swimming pools. This study provides useful information to improve the
safety of swimming pool water and deduce the risk of protozoan infections.
PMID- 28506035
TI - Simultaneous Molecular Detection of Cryptosporidium and Cyclospora from Raw
Vegetables in Korea.
AB - Cryptosporidium and Cyclospora are well-known coccidian protozoa that can cause
waterborne and foodborne diarrheal illnesses. There have been a few reports
regarding contamination in different vegetables with Cryptosporidium, but no data
are available regarding the sources of Cyclospora infections in Korea. In the
present study, we collected 6 kinds of vegetables (perilla leaves, winter-grown
cabbages, chives, sprouts, blueberries, and cherry tomatoes) from July 2014 to
June 2015, and investigated contamination by these 2 protozoa using multiplex
quantitative real-time PCR. Among 404 vegetables, Cryptosporidium and Cyclospora
were detected in 31 (7.7%) and 5 (1.2%) samples, respectively. In addition,
Cryptosporidium was isolated from all 6 kinds of vegetables, whereas Cyclospora
was detected in 4 kinds of vegetables (except perilla leaves and chives).
Cryptosporidium (17.8%) and Cyclospora (2.9%) had the highest detection rates in
chives and winter-grown cabbages, respectively. Cryptosporidium was detected all
year long; however, Cyclospora was detected only from October to January. In 2
samples (sprout and blueberry), both Cryptosporidium and Cyclospora were
detected. Further investigations using TaqI restriction enzyme fragmentation and
nested PCR confirmed Cryptosporidium parvum and Cyclospora cayetanensis,
respectively. In conclusion, we detected C. cayetanensis in vegetables for the
first time in Korea. This suggests that screening should be employed to prevent
these protozoal infections in Korea.
PMID- 28506036
TI - Influenza M1 Virus-Like Particles Consisting of Toxoplasma gondii Rhoptry Protein
4.
AB - Toxoplasma gondii infections occur throughout the world, and efforts are needed
to develop various vaccine candidates expressing recombinant protein antigens. In
this study, influenza matrix protein (M1) virus-like particles (VLPs) consisting
of T. gondii rhoptry antigen 4 (ROP4 protein) were generated using baculovirus
(rBV) expression system. Recombinant ROP4 protein with influenza M1 were cloned
and expressed in rBV. SF9 insect cells were coinfected with recombinant rBVs
expressing T. gondii ROP4 and influenza M1. As the results, influenza M1 VLPs
showed spherical shapes, and T. gondii ROP4 protein exhibited as spikes on VLP
surface under transmission electron microscopy (TEM). The M1 VLPs resemble
virions in morphology and size. We found that M1 VLPs reacted with antibody from
T. gondii-infected mice by western blot and ELISA. This study demonstrated that
T. gondii ROP4 protein can be expressed on the surface of influenza M1 VLPs and
the M1 VLPs containing T. gondii ROP4 reacted with T. gondii-infected sera,
indicating the possibility that M1 VLPs could be used as a coating antigen for
diagnostic and/or vaccine candidate against T. gondii infection.
PMID- 28506037
TI - Diversity of vir Genes in Plasmodium vivax from Endemic Regions in the Republic
of Korea: an Initial Evaluation.
AB - Variant surface antigens (VSAs) encoded by pir families are considered to be the
key proteins used by many Plasmodium spp. to escape the host immune system by
antigenic variation. This attribute of VSAs is a critical issue in the
development of a novel vaccine. In this regard, a population genetic study of vir
genes from Plasmodium vivax was performed in the Republic of Korea (ROK). Eighty
five venous blood samples and 4 of the vir genes, namely vir 27, vir 21, vir 12,
and vir 4, were selected for study. The number of segregating sites (S), number
of haplotypes (H), haplotype diversity (Hd), DNA diversity (pi and Thetaw), and
Tajima's D test value were conducted. Phylogenetic trees of each gene were
constructed. The vir 21 (S=143, H=22, Hd=0.827) was the most genetically diverse
gene, and the vir 4 (S=6, H=4, Hd=0.556) was the opposite one. Tajima's D values
for vir 27 (1.08530, P>0.1), vir 12 (2.89007, P<0.01), and vir 21 (0.40782,
P>0.1) were positive, and that of vir 4 (-1.32162, P>0.1) was negative. All
phylogenetic trees showed 2 clades with no particular branching according to the
geographical differences and cluster. This study is the first survey on the vir
genes in ROK, providing information on the genetic level. The sample sequences
from vir 4 showed a clear difference to the Sal-1 reference gene sequence,
whereas they were very similar to those from Indian isolates.
PMID- 28506038
TI - PCR-RFLP for Rapid Subtyping of Plasmodium vivax Korean Isolates.
AB - Vivax malaria reemerged in Korea in 1993 and the outbreak has been continued with
fluctuating numbers of annual indigenous cases. Understanding the nature of the
genetic population of Plasmodium vivax circulating in Korea is beneficial for the
knowledge of the nationwide parasite heterogeneity and in the implementation of
malaria control programs in the country. Previously, we analyzed polymorphic
nature of merozoite surface protein-1 (MSP-1) and MSP-3alpha in Korean P. vivax
population and identified the Korean P. vivax population has been diversifying
rapidly, with the appearance of parasites with new genetic subtypes, despite the
recent reduction of the disease incidence. In the present study, we developed
simple PCR-RFLP methods for rapid subtyping of MSP-1 and MSP-3alpha of Korean P.
vivax isolates. These PCR-RFLP methods were able to easily distinguish each
subtype of Korean P. vivax MSP-1 and MSP-3alpha with high accuracy. The PCR-RFLP
subtyping methods developed here would be easily applied to massive
epidemiological studies for molecular surveillance to understand genetic
population of P. vivax and to supervise the genetic variation of the parasite
circulating in Korea.
PMID- 28506039
TI - Plasma D-dimer Can Effectively Predict the Prospective Occurrence of Ascites in
Advanced Schistosomiasis Japonica Patients.
AB - China still has more than 30,000 patients of advanced schistosomiasis while new
cases being reported consistently. D-dimer is a fibrin degradation product. As
ascites being the dominating symptom in advanced schistosomiasis, the present
study aimed to explore a prediction model of ascites with D-dimer and other
clinical easy-achievable indicators. A case-control study nested in a prospective
cohort was conducted in schistosomiasis-endemic area of southern China. A total
of 291 patients of advanced schistosomiasis were first investigated in 2013 and
further followed in 2014. Information on clinical history, physical examination,
and abdominal ultrasonography, including the symptom of ascites was repeatedly
collected. Result showed 44 patients having ascites. Most of the patients'
ascites were confined in the kidney area with median area of 20 mm2. The level of
plasma D-dimer and pertinent liver function indicators were measured at the
initial investigation in 2013. Compared with those without ascites, cases with
ascites had significantly higher levels of D-dimer (0.71+/-2.44 MUg/L vs 0.48+/
2.12 MUg/L, P=0.005), as well ALB (44.5 vs 46.2, g/L) and Type IV collagen (50.04
vs 44.50 MUg/L). Receiver operating characteristic curve analyses indicated a
moderate predictive value of D-dimer by its own area under curve (AUC) of 0.64
(95% CI: 0.54-0.73) and the cutoff value as 0.81 MUg/L. Dichotomized by the
cutoff level, D-dimer along with other categorical variables generated a
prediction model with AUC of 0.76 (95% CI: 0.68-0.89). Risks of patients with
specific characteristics in the prediction model were summarized. Our study
suggests that the plasma D-dimer level is a reliable predictor for incident
ascites in advanced schistosomiasis japonica patients.
PMID- 28506040
TI - Codon Usage Patterns of Tyrosinase Genes in Clonorchis sinensis.
AB - Codon usage bias (CUB) is a unique property of genomes and has contributed to the
better understanding of the molecular features and the evolution processes of
particular gene. In this study, genetic indices associated with CUB, including
relative synonymous codon usage and effective numbers of codons, as well as the
nucleotide composition, were investigated in the Clonorchis sinensis tyrosinase
genes and their platyhelminth orthologs, which play an important role in the
eggshell formation. The relative synonymous codon usage patterns substantially
differed among tyrosinase genes examined. In a neutrality analysis, the
correlation between GC12 and GC3 was statistically significant, and the
regression line had a relatively gradual slope (0.218). NC-plot, i.e., GC3 vs
effective number of codons (ENC), showed that most of the tyrosinase genes were
below the expected curve. The codon adaptation index (CAI) values of the
platyhelminth tyrosinases had a narrow distribution between 0.685/0.714 and
0.797/0.837, and were negatively correlated with their ENC. Taken together, these
results suggested that CUB in the tyrosinase genes seemed to be basically
governed by selection pressures rather than mutational bias, although the latter
factor provided an additional force in shaping CUB of the C. sinensis and
Opisthorchis viverrini genes. It was also apparent that the equilibrium point
between selection pressure and mutational bias is much more inclined to selection
pressure in highly expressed C. sinensis genes, than in poorly expressed genes.
PMID- 28506041
TI - Identification of Tick Species Collected from Wild Boars and Habitats of Wild
Boars and Domestic Pigs in the Republic of Korea.
AB - Tick is one of the most important arthropods in the transmission of vector-borne
diseases. In this study, we investigated the abundance and species of ticks
associated with swine and their habitats to assess the risk of spread of tick
borne diseases in host species, such as wild boars. Ticks were collected from 24
grazing or traditionally reared domestic pig farms and 8 habitats of wild boars
in 8 provinces and 1 city in the Republic of Korea, by using the dragging and
flagging methods. Ticks were also collected directly from 49 wild boars by using
fine forceps. A total of 9,846 hard ticks were collected, including 4,977
Haemaphysalis longicornis, 4,313 Haemaphysalis flava, 508 Ixodes nipponensis, 1
Ixodes turdus, and 47 Amblyomma testudinarium. A total of 240 hard ticks were
collected from 49 wild boars, including 109 H. flava, 84 H. longicornis, and 47
A. testudinarium. A total of 578 hard ticks were collected from areas around
domestic pig farms. Only 2 hard tick species, 546 H. longicornis and 32 H. flava,
were collected from these areas. A total of 9,028 hard ticks were collected from
wild boars of 8 habitats, including 4,347 H. longicornis, 4,172 H. flava, 508 I.
nipponensis, and 1 I. turdus. A. testudinarium was collected only from wild
boars, and I. nipponensis and I. turdus were collected only from the habitats of
wild boars.
PMID- 28506042
TI - Life Cycle of Dermacentor everestianus Hirst, 1926 (Acari: Ixodidae) under
Laboratory Conditions.
AB - This study investigated the development characteristics of Dermacentor
everestianus under laboratory conditions. The time taken for D. everestianus to
complete the whole life cycle was 110.2 days on average, and the average
developmental durations of larvae and nymphs were 17.1 days and 29.5 days,
respectively. The summation of the prefeeding, feeding, and preoviposition
periods of females was 17.8 days, and the oviposition and egg incubation lasted
for 18.1 days and 27.7 days, respectively. A highly positive correlation was
observed between the weight of engorged female and the number of egg mass laid
(r=0.947). The reproductive efficiency index and the reproductive fitness index
were 7.1 and 6.1, respectively.
PMID- 28506043
TI - First Paleoparasitological Report on the Animal Feces of Bronze Age Excavated
from Shahr-e Sukhteh, Iran.
AB - Shahr-e Sukhteh (meaning burnt city in Persian) in Iran is an archeological site
dated back to around 3,200-1,800 BC. It is located in Sistan and Baluchistan
Province of Iran and known as the junction of Bronze Age trade routes crossing
the Iranian plateau. It was appointed as current study area for
paleoparasitological investigations. Excavations at this site have revealed
various archeological materials since 1967. In the present study, sheep and
carnivore coprolites excavated from this site were analyzed by means of
rehydration technique using TSP solution for finding helminth eggs. Dicrocoelium
dendriticum, Capillaria sp., and Taenia sp. eggs were identified, while some
other objects similar to Anoplocephalidae and Toxocara spp. eggs were also
retrieved from the samples but their measured parameters did not match those of
these species. The present paper illustrates the first paleoparasitological
findings of Bronze Age in eastern Iran supporting the economic activities,
peopling, and communication as well as the appropriate condition for zoonotic
helminthiasis life cycle in Shahr-e Sukhteh archeological site.
PMID- 28506044
TI - Seroprevalence and Risk Factors of Toxoplasma gondii Infection among Cat Sitters
in Korea.
AB - The seroprevalence of human toxoplasmosis has been increasing in Korea, and it is
controversial whether cats are an important infection source or not. This study
was performed to evaluate the seroprevalence of Toxoplasma gondii infection in a
high risk group (cat sitters) and to determine the possible importance of cats as
an infection source in Korea. Risk factors, including the age, sex, and diet of
cat sitters, their contact experience and contact frequency with stray cats, and
origin, number, and outdoor activity of their pet cats, were analyzed using
structured questionnaires. A total of 673 serum samples from people who have
frequent contact with cats (high risk group) and 1,114 samples from general
people (low risk group) were examined for specific IgG antibodies against T.
gondii by ELISA. The results revealed that the overall seroprevalence of T.
gondii infection was 7.4% (n=1,787). The seroprevalence among low risk group was
8.0% (89/1,114), whereas that among high risk group was rather lower 6.4%
(43/673), though this difference was statistically not significant (P=0.211).
Among the risk factors, only the outdoor activity of pet cats was important;
people having cats with outdoor activities revealed 2 times higher seroprevalence
than people having cats with only indoor activities (P=0.027). In conclusion, the
seroprevalence of T. gondii was not significantly different between the high risk
group and low risk group, and the importance of cats as a source of infection in
Korea is questionable.
PMID- 28506047
TI - First Report of Clavinema mariae (Nematoda: Philometridae) in Cultured Rockfish,
Sebastes schlegeli, in Cheonsuman (Bay), the Republic of Korea.
AB - In July 2012, philometrid nematodes were discovered in cultured rockfish
(Sebastes schlegeli) in Cheonsuman (Bay), the Republic of Korea. The nematodes
were detected in the epithelial tissues of the rockfish and were identified as
Clavinema mariae based on morphological studies using light and scanning electron
microscopy. They revealed the characteristics same as previously identified C.
mariae, notably having a long body with narrow posterior half, no caudal
projection, a cylindrical-shaped esophagus, a well-developed anterior bulbous
part of the esophagus, cephalic papillae, and a dorsal esophageal gland. This is
the first confirmation of C. mariae infection in rockfish in Korea.
PMID- 28506048
TI - Indoor Occurrence of the Ghost Ant Tapinoma melanocephalum (Hymenoptera:
Formicidae) in Urban Homes in Korea.
AB - The ghost ant Tapinoma melanocephalum is a common household pest worldwide. The
present study examined the occurrence of the species in urban homes in Korea.
During the period of September 2014 to January 2016, T. melanocephalum workers
were collected from 58 homes at 29 different localities using bait traps with 10%
sugar solution. The species was widely distributed throughout urban homes at 29
different localities, and the indoor occurrence of T. melanocephalum was highest
in Seoul (32.7%) and metropolitan areas of Gyeonggi-do (Province) (29.3%). The
indoor incidence rate of T. melanocephalum peaked in September (22.8%), remained
moderate from October through April, and peaked again in May (15.7%). In
contrast, a low incidence was observed from June to August (7.0%). The present
study provides evidence that native ants, such as T. melanocephalum, are
potential indoor pests of homes in Korea throughout the year.
PMID- 28506045
TI - Serological and Molecular Detection of Toxoplasma gondii and Babesia microti in
the Blood of Rescued Wild Animals in Gangwon-do (Province), Korea.
AB - Infections of Toxoplasma gondii and Babesia microti are reported in many wild
animals worldwide, but information on their incidence and molecular detection in
Korean wild fields is limited. In this study, the prevalence of T. gondii and B.
microti infection in blood samples of 5 animal species (37 Chinese water deer, 23
raccoon dogs, 6 roe deer, 1 wild boar, and 3 Eurasian badgers) was examined
during 2008-2009 in Gangwon-do (Province), the Republic of Korea (=Korea) by
using serological and molecular tests. The overall seropositivity of T. gondii
was 8.6% (6/70); 10.8% in Chinese water deer, 4.3% in raccoon dogs, and 16.7% in
roe deer. PCR revealed only 1 case of T. gondii infection in Chinese water deer,
and phylogenic analysis showed that the positive isolate was practically
identical to the highly pathogenetic strain type I. In B. microti PCR, the
positive rate was 5.7% (4/70), including 2 Chinese water deer and 2 Eurasian
badgers. Phylogenetic analysis results of 18S rRNA and the beta-tubulin gene
showed that all positive isolates were US-type B. microti. To our knowledge, this
is the first report of B. microti detected in Chinese water deer and Eurasian
badger from Korea. These results indicate a potentially high prevalence of T.
gondii and B. microti in wild animals of Gangwon-do, Korea. Furthermore, Chinese
water deer might act as a reservoir for parasite infections of domestic animals.
PMID- 28506046
TI - Interaction between Trichomonas vaginalis and the Prostate Epithelium.
AB - Most men infected with Trichomonas vaginalis are asymptomatic and can remain
undiagnosed and untreated. This has been hypothesized to result in chronic
persistent prostatic infection. Adhesion of the protozoan organisms to mucosal
cells is considered a first and prerequisite step for T. vaginalis infection.
Adhesion of T. vaginalis to prostate epithelial cells has not yet been observed;
however, there are several reports about inflammation of prostate epithelial
cells induced by T. vaginalis. The aim of this study was to investigate whether
adhesion and cytotoxicity of T. vaginalis are involved in inflammation of
prostate epithelial cells. When RWPE-1 cells were infected with T. vaginalis
(1:0.4 or 1:4), adhesion of T. vaginalis continuously increased for 24 hr or 3
hr, respectively. The cytotoxicity of prostate epithelial cells infected with T.
vaginalis (RWPE-1: T. vaginalis=1:0.4) increased at 9 hr; at an infection ratio
of 1:4, cytotoxicity increased after 3 hr. When the RWPE-1 to T. vaginalis ratio
was 1:0.4 or 1:4, production of IL-1beta, IL-6, CCL2, and CXCL8 also increased.
Epithelial-mesenchymal transition (EMT) was verified by measuring decreased E
cadherin and increased vimentin expression at 24 hr and 48 hr. Taken together,
the results indicate that T. vaginalis adhered to prostate epithelial cells,
causing cytotoxicity, pro-inflammatory cytokine production, and EMT. Our findings
suggest for the first time that T. vaginalis may induce inflammation via adhesion
to normal prostate epithelial cells.
PMID- 28506049
TI - [Laparoscopic Non-Ischemic Partial Nephrectomy Using a Microwave Tissue
Coagulator : A Single-Institutional Study].
AB - We retrospectively investigated the surgical outcomes of renal cell carcinoma
(RCC), perioperative complications, and residual renal function in patients
receiving laparoscopic non-ischemic partial nephrectomy using a microwave tissue
coagulator (MTC). Between January 2002 and December 2015, laparoscopic non
ischemic partial nephrectomy using MTC was performed in 49 patients. The
histological diagnosis was RCC in 38 patients, angiomyolipoma in 4, oncocytoma in
2, and others in 5. A histologicallyproven positive surgical margin was observed
in 1 (2.0%). Postoperative urine leakage occurred in 1, and it was treated
conservatively. The mean follow-up period was 32.0 months. Although there was no
patient who died of RCC, local recurrence occurred in 2 patients (4.1%) during
the follow-up period. One of these 2 patients had a positive surgical margin.
Deterioration of the residual renal function was not observed. Laparoscopic non
ischemic partial nephrectomy using MTC was safe and useful in terms of cancer
control and preservation of renal function.
PMID- 28506050
TI - [A Clinicopathologic Study of 6 Patients with Histologically Pure Seminoma But
Elevated Serum Alpha-Fetoprotein].
AB - Histologically pure seminoma with elevated alpha-fetoprotein (AFP), so-called AFP
positive seminoma, is rare. It is recommended that patients with AFP-positive
seminoma be managed as non-seminoma, but the clinical features and prognosis of
this disease are not fully understood. In this study, we retrospectively analyzed
6 cases of metastatic AFP-positive seminoma at Tsukuba University Hospital (TUH).
AFP was elevated before induction chemotherapy in 4 patients with an average of
1,372 ng/ml. In the remaining 2 patients, AFP became elevated during or after
induction chemotherapy. In all 4 patients examined, AFPL3% was abnormally
increased. As induction chemotherapy, all patients received bleomycin, etoposide
and cisplatin (BEP), which was then followed by etoposide, ifosfamide and
cisplatin (VIP) in 3 patients. After or during induction chemotherapy, 3 patients
suffered from disease progression accompanied by AFP elevation. All 3 were
treated by salvage chemotherapy and surgery. Four patients underwent
retroperitoneal lymph node dissection (RPLND) after induction chemotherapy ; the
pathological findings were necrosis in 3 patients, and viable nonseminomatous
cancer in 1 patient. Furthermore, RPLND was performed as salvage surgery in 3
patients ; the pathological findings were necrosis, viable nonseminomatous cancer
and teratoma with malignant transformation, respectively. The 5-year progression
free survival rate of the 6 patients was 50%, which is somewhat inferior to that
of poor-prognosis non-seminoma patients treated at TUH. One patient ultimately
died of cancer, and the remaining 5 are in remission with a median follow-up of
58 months. The present study demonstrates that AFP-positive seminoma patients
have a higher risk of relapse compared to non-seminoma patients.
PMID- 28506051
TI - [A Case of Thyroid-Like Follicular Carcinoma of the Kidney].
AB - A 51-year-oldwoman with a right renal mass was referredto our hospital.
Computedtomographic (CT) scan demonstrated a 30 mm-diameter renal mass with
delayed enhancement. She underwent a robotassistedlaparoscopic right partial
nephrectomy. The pathological examination showedthat tumor cells with
eosinophilic, clear cytoplasm formedtubules of various sizes containing colloid
like material, which resembled the findings of thyroidfollicular carcinoma. The
tumor was immunoreactive for vimentin andcytokeratin (CK) 7, whereas it
lackedreactivity for thyroidtranscription factor-1 (TTF-1) or thyroglobulin. No
tumors were detectedin the thyroidglandor other organs of the patient.
Subsequently, the diagnosis of thyroidlike follicular carcinoma of the kidney
(TLFCK) was determined. At 4 months postoperatively, the patient is alive with no
evidence of disease recurrence. TLFCK is an extremely rare subtype of renal
cancer, and only 26 cases have been reportedpreviously. We provide a brief
literature review on this cancer.
PMID- 28506052
TI - [Renal Cell Carcinoma with Retroperitoneal Metastases and Renal Invasion from
Breast Cancer : A Case Report].
AB - A 67-year-old female was hospitalized with back pain. Computed tomography (CT)
incidentally revealed a tumor in her left kidney tumor (33 mm) and bilateral
breast tumors. She underwent a breast biopsy and was diagnosed with breast cancer
(invasive lobular cancer, cT2N0M0). The renal tumor was suspected to be clear
cell carcinoma, cT1aN0M0, based on contrast-enhanced CT. Surgery was considered
necessary for both the breast cancer and renal tumor. First, laparoscopic radical
nephrectomy was performed for the renal tumor. However, the lateroconal fascia
adhered strongly to the perirenal fat, and so simple nephrectomy was carried out
after conversion to open surgery. The perirenal fat was also excised after the
nephrectomy. A histopathological examination revealed clear cell carcinoma and
renal invasion by invasive lobular cancer cells. Also, scattered metastases were
detected in the perirenal fat and the lateroconal fascia. So, it was considered
that retroperitoneal metastases from the breast cancer had directly invaded the
kidney. After the operation, the patient received hormonal therapy for her breast
cancer, and she was still alive and symptom-free 5 months after the operation.
PMID- 28506053
TI - [Laparoscopic Pyelolithotomy in a Horseshoe Kidney : A Case Report and Review of
the Literature].
AB - A 76-year-old man was introduced to our department with a right kidney stone. On
the basis of further examination, he was diagnosed with a 23 mm right kidney
stone accompanied with a horseshoe kidney. Retrograde pyelography and diuretic
renogram revealed a non-obstructed right ureteropelvic junction. Finally, we
chose laparoscopic pyelolithotomy via peritoneal approach because the stone was
large and accompanied with a horseshoe kidney. The surgery took 165 minutes and
the estimated blood loss was 25 ml. There were no minor or major complications.
Because horseshoe kidney has anatomical abnormalities, it seems to be necessary
to consider a different treatment strategy from that of an upper urinary tract
stone in a healthy kidney. We assume that laparoscopic pyelolithotomy is an
effective and safe procedure for renal pelvic stones in the case of a horseshoe
kidney.
PMID- 28506054
TI - [Penile Tuberculosis : A Case Report].
AB - A 66-year-old man presented with a chief complaint of glans penis pain,
induration, and discharge of pus. He was prescribed a course of antibiotics, but
the condition persisted despite treatment. Thus, we differrentially diagnosed the
patient with penile tuberculosis and pyoderma gangrenosum, and performed a biopsy
of the penis. The biopsy result was thickening of the horny layer epidermis with
only a foreign body granuloma composed of inflammatory cells, and did not lead to
a definitive diagnosis. Thoraca-abdominal computed tomography revealed axillary
lymphadenopathy with necrosis. Suspecting tuberculosis lymphadenitis, we
performed T-spot and QuantiFERONtests. The result was T-spot negative and
QuantiFERONpositive, so we diagnosed the patient with penile tuberculosis, and
started antituberculosis medication. In about half a year after the start of
treatment the symptoms subsided, and lymphadenopathy showed reduction.
PMID- 28506057
TI - Liquid Spray Dielectric Barrier Discharge Induced Plasma-Chemical Vapor
Generation for the Determination of Lead by ICPMS.
AB - In the present study, a novel and sensitive liquid spray dielectric barrier
discharge induced plasma-chemical vapor generation technique (LSDBD-CVG) is
developed for the determination of lead concentration by inductively coupled
plasma mass spectrometry (ICPMS). The dissolved Pb2+ is readily converted to
volatile species by LSDBD plasma induced chemical processes in the presence of 5%
(v/v) formic acid in a supporting electrolyte (HCl, 0.01 mol L-1). In this LSDBD
approach, the sample solution is converted to aerosol and simultaneously mixed
with the DBD plasma generated at the nozzle of a pneumatic nebulizer, which
greatly facilitates Pb vapor generation because of the enhanced interaction of
sprayed analytes and the plasma. Optimal conditions for LSDBD-CVG were
identified, and the interference effects from other metal ions were assessed.
Under optimized conditions, the detection limit of Pb was found to be 0.003 MUg L
1. The repeatability, expressed as the relative standard deviation (RSD) of the
peak height, for the five replicate measurements of 0.03 and 1 MUg L-1 lead
standard, were 2.1% and 1.7%, respectively. Compared with other vapor generation
methods, this new LSDBD-CVG offers several advantages including no requirement of
unstable reagents, fast response, and easy coupling with flow injection, along
with high tolerance for coexisting ions. The accuracy of the proposed method is
demonstrated by successful analysis of Pb in reference material of stream
sediment (GBW07311), soil (GBW07403), basalt (BCR-2), and simulated water sample
(GBW08601). The proposed LSDBD-CVG extends the scope of elements accessible by
plasma-CVG and provides an alternative efficient green approach for the vapor
generation of Pb.
PMID- 28506055
TI - Clinical features and outcomes of patients with hepatocellular carcinoma
complicated with bile duct invasion.
AB - BACKGROUND/AIMS: Little is known about the treatment or outcomes of
hepatocellular carcinoma (HCC) complicated with bile duct invasion. METHODS: A
total of 247 consecutive HCC patients with bile duct invasion at initial
diagnosis were retrospectively included. RESULTS: The majority of patients had
Barcelona Clinic Liver Cancer (BCLC) stage C HCC (66.8%). Portal vein tumor
thrombosis was present in 166 (67.2%) patients. Median survival was 4.1 months.
Various modalities of treatment were initially employed including surgical
resection (10.9%), repeated transarterial chemoembolization (TACE) (42.5%), and
conservative management (42.9%). Among the patients with obstructive jaundice
(n=88), successful biliary drainage was associated with better overall survival
rate. Among the patients with BCLC stage C, overall survival differed depending
on the initial treatment for HCC; surgical resection, TACE, systemic
chemotherapy, and conservative management showed overall survival rates of 11.5,
6.0 ,2.4, and 1.6 months, respectively. After adjusting for confounders, surgical
resection and repeated TACE were significant prognostic factors for HCC patients
with bile duct invasion (hazard ratios 0.47 and 0.39, Ps <0.001, respectively).
CONCLUSIONS: The survival of HCC patients with bile duct invasion at initial
diagnosis is generally poor. However, aggressive treatments for HCC such as
resection or biliary drainage may be beneficial therapeutic options for patients
with preserved liver function.
PMID- 28506058
TI - Differential Protein Analysis of IPEC-J2 Cells Infected with Porcine Epidemic
Diarrhea Virus Pandemic and Classical Strains Elucidates the Pathogenesis of
Infection.
AB - Porcine epidemic diarrhea (PED) re-emerged in China in late 2010 and has now
become widespread. Accumulated evidence indicates that this large-scale outbreak
of diarrhea was caused by variants of the highly virulent porcine epidemic
diarrhea virus (PEDV). A pandemic PEDV YC2014 strain (YC2014) was isolated from
clinical samples. An iTRAQ-based comparative quantitative proteomic study of IPEC
J2 cells infected with YC2014 and a classical CV777 strain (CV777) was performed
to determine the differences between pandemic and classical PEDV strain
infection. Totals of 353 and 299 differentially expressed proteins were
identified upon YC2014 and CV777 infection, respectively. The canonical pathways
and functional networks involved in both PEDV infections were analyzed. The
results indicated that the PEDV suppressed protein synthesis of IPEC-J2 cells
through down-regulation of the PI3K-AKT/mTOR signaling pathways. Infection with
YC2014 could activate the JAK-STAT signaling pathway and the NF-kappaB pathway
more intensively than CV777. YC2014 could activate NF-kappaB pathway more
intensively than CV777. On the basis of differentially expressed proteins, we
propose that PEDV might disrupt apoptosis and may elicit stronger inflammatory
cascades as well. This study might contribute to an understanding of the
pathogenesis of PEDV infection and aid in the development of effective preventive
and control vaccines.
PMID- 28506056
TI - Risk score model for the development of hepatocellular carcinoma in treatment
naive patients receiving oral antiviral treatment for chronic hepatitis B.
AB - BACKGROUND/AIMS: This study aimed to develop and validate a risk prediction model
for the development of hepatocellular carcinoma (HCC) in treatment-naive patients
receiving oral antiviral treatment for chronic hepatitis B (CHB). METHODS: We
investigated 2,061 Korean treatment-naive patients with CHB treated with
entecavir as an initial therapy. A risk score model for HCC development was
developed based on multivariable Cox regression model in a single center (n=990)
and was validated using the time-dependent area under the receiver operating
characteristic curve (AUROC) in three other centers (n=1,071). The difference of
HCC development among risk groups (low, intermediate, and high) categorized by
risk score was also investigated. RESULTS: The cumulative incidence rates of HCC
at 5 years were 11.2% and 8.9% in the testing and validation cohorts,
respectively. HCC-Risk Estimating Score in CHB patients Under Entecavir (HCC
RESCUE) is formulated as (age+15*gender [female=0 / male=1]+23*cirrhosis
[absence=0 / presence=1]). The AUROCs at 1 year, 3 years, and 5 years were 0.82,
0.81, and 0.81, respectively, in the validation cohort. A significant difference
of HCC development in each risk group was determined by the 5-year HCC risk score
in the validation cohort (low risk group, 2.1%; intermediate risk group, 9.3%;
high risk group, 41.2%, p<0.001). CONCLUSIONS: The study presents a new risk
score model with a good ability to predict HCC development and determine high
risk patients for HCC development consisting of readily available clinical
factors in treatment-naive CHB patients receiving entecavir.
PMID- 28506060
TI - Remobilization Dynamics of Caffeine, Ciprofloxacin, and Propranolol following
Evaporation-Induced Immobilization in Porous Media.
AB - Changing weather conditions can cause cycles of wetting and drying in the
unsaturated zone. When porewater evaporates, any nonvolatile solutes present in
the pores will be driven to adsorb and ultimately precipitate on solid surfaces.
When media are subsequently resaturated through rainfall infiltration, the
remobilization of solutes likely depends on both the hydraulics of resaturation
and the dynamics of dissolution processes. The focus of this work was to study
the dynamics of remobilization of three different emerging contaminants
(caffeine, ciprofloxacin, and propranolol) and two model compounds (fluorescein
and sulforhodamine B) from porous media following evaporation of porewater.
Remobilization column experiments were conducted to study this phenomenon and
were evaluated using a finite difference model developed to simulate the
adsorption-desorption dynamics during resaturation and elution. Results indicate
that dissolution dynamics become increasingly important with increasing
adsorption affinity for solid surfaces. Trends in observed elution behavior are
not well-predicted from chemical properties, such as solubility. One of the most
significant observations of the work is the presence of spikes in elution
concentrations well above initial porewater concentration, resulting from the
hydraulics of the resaturation process. The effect is most significant in highly
mobile compounds that exhibit low adsorption affinity for solid surfaces.
PMID- 28506061
TI - An Elastic Hydrogen-Bonded Cross-Linked Organic Framework for Effective Iodine
Capture in Water.
AB - A crystalline microporous hydrogen-bonded cross-linked organic framework has been
developed through covalent photo-cross-linking of molecular monomers that are
assembled in a crystalline state. The elastic framework expands its void space to
adsorb iodine rapidly with a high uptake capacity in an aqueous environment as
well as recovering its crystalline form after the release of iodine.
PMID- 28506062
TI - LC-MS Untargeted Metabolomics To Explain the Signal Metabolites Inducing Browning
in Fresh-Cut Lettuce.
AB - Enzymatic browning is one of the main causes of quality loss in lettuce as a
prepared and ready-to-eat cut salad. An untargeted metabolomics approach using
UPLC-ESI-QTOF-MS was performed to explain the wound response of lettuce after
cutting and to identify the metabolites responsible of browning. Two cultivars of
Romaine lettuce with different browning susceptibilities were studied at short
time intervals after cutting. From the total 5975 entities obtained from the raw
data after alignment, filtration reduced the number of features to 2959, and the
statistical analysis found that only 1132 entities were significantly different.
Principal component analysis (PCA) clearly showed that these samples grouped
according to cultivar and time after cutting. From those, only 15 metabolites
belonging to lysophospholipids, oxylipin/jasmonate metabolites, and phenolic
compounds were able to explain the browning process. These selected metabolites
showed different trends after cutting; some decreased rapidly, others increased
but decreased thereafter, whereas others increased during the whole period of
storage. In general, the fast-browning cultivar showed a faster wound response
and a higher raw intensity of some key metabolites than the slow-browning one.
Just after cutting, the fast-browning cultivar contained 11 of the 15 browning
associated metabolites, whereas the slow-browning cultivar only had 5 of them.
These metabolites could be used as biomarkers in breeding programs for the
selection of lettuce cultivars with lower browning potential for fresh-cut
applications.
PMID- 28506059
TI - Application of Liquid Chromatography-Tandem Mass Spectrometry To Determine
Urinary Concentrations of Five Commonly Used Low-Calorie Sweeteners: A Novel
Biomarker Approach for Assessing Recent Intakes?
AB - Although the use of low-calorie sweeteners (LCSs) is widespread, methods of
assessing consumption within free-living populations have inherent limitations.
Five commonly consumed LCSs, namely, acesulfame-K, saccharin, sucralose,
cyclamate, and steviol glycosides, are excreted via the urine, and therefore a
urinary biomarker approach may provide more objective LCS intake data. A LC-ESI
MS/MS method of simultaneously determining acesulfame-K, saccharin, sucralose,
cyclamate, and the excretory metabolite of steviol glycosides, steviol
glucuronide, in human urine was developed and validated. Linearity was observed
over a concentration range of 10-1000 ng/mL with coefficients of determination
ranging from 0.9969 to 0.9997. Accuracy ranged from 92 to 104%, and intrabatch
and interday precisions were within acceptable limits with %CV below 8% for all
compounds. A double-blind, randomized crossover dose-response study was conducted
to assess the usefulness of urinary LCS excretions (from both fasting spot and a
full 24-h urine collection) for investigating recent intakes. Both modes of
sampling were useful for distinguishing between the three short-term intakes of
acesulfame-K, saccharin, cyclamates, and steviol glycosides (p < 0.001), whereas
for sucralose, urinary concentrations were useful for distinguishing between low
(0.1% ADI) and high doses (10% ADI) only (p < 0.001). In summary, this biomarker
approach may be useful for assessing intakes of five commonly consumed LCSs.
PMID- 28506064
TI - Ice-Melting Dynamics: The Role of Protons and Interfacial Geometry.
AB - The surface of ice plays a significant role in melting. To better understand the
role of the surface, we studied the melting of ice using infrared imaging and pH
sensitive dyes. Ice was allowed to melt in baths of water of varying depths. When
the ice melted in a high level of room-temperature water, equal to the height of
the ice, the conventional melting pattern appeared. When the ice melted in a
chamber with a lower water level, the melting pattern was unexpected. Seconds
after the ice was placed in the water, localized regions of low-temperature water
appeared around the perimeter of the ice. These regions grew radially outward and
seemed to originate as streams coming from inside the ice. Those streams
contained high concentrations of protons, as indicated by the color change of a
pH-sensitive dye initially placed in the water surrounding the ice. This
observation, together with the temperature distribution and ice-shape changes
during melting implied that the streams may be propelled by protons from inside
the ice. In contrast to conventional melting, which progresses from the outer
surface inward, the stream-melting pattern implies a melting process originating
inside the ice.
PMID- 28506063
TI - Extensive Transformation of the Pharmaceutical Carbamazepine Following Uptake
into Intact Tomato Plants.
AB - Carbamazepine (CBZ) is an antiepileptic drug which is persistent in wastewater
treatment plants and the environment. It has been frequently detected in plant
material after irrigation with treated wastewater. To date, little information
is, however, available on the transformation of CBZ in plants. In the present
study, the uptake, translocation, and transformation of CBZ was studied in
hydroponically grown tomato plants. After 35 days of exposure >80% of the total
spiked amount of CBZ was taken by the tomato plants and mainly stored in the
leaves. A total of 11 transformation products (TP) (mainly phase-I) were
quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and their
total amount corresponded to 33% of the CBZ taken up. The ratio of CBZ
metabolites to CBZ was highest in fruits (up to 2.5) and leaves (0.5), suggesting
an intensive transformation of CBZ in these compartments. Further 10 TPs (phase-I
and II) were identified by LC-high resolution mass spectrometry screening, likely
comprising another 12% of CBZ. On the basis of these experiments and on an
experiment with CBZ-10,11-epoxide a transformation pathway of CBZ in intact
tomato plants is proposed that involves epoxidation, hydrolysis, hydroxylation,
ring contraction, or loss of the carbamoyl group, followed by conjugation to
glucose or cysteine, but also reduction of CBZ. This transformation pathway and
analytical data of CBZ transformation products allow for their determination also
in field grown vegetable and for the generation of more accurate exposure data of
consumers of vegetable irrigated with treated municipal wastewater.
PMID- 28506065
TI - Opening of an Accessible Microporosity in an Otherwise Nonporous Metal-Organic
Framework by Polymeric Guests.
AB - The development of highly porous metal-organic frameworks (MOFs) is greatly
sought after, due to their wide range of applications. As an alternative to the
development of new structures, we propose to obtain new stable configurations for
flexible MOFs by insertion of polymeric guests. The guests prevent the otherwise
spontaneous closing of the host frameworks and result in stable opened forms.
Introduced at a fraction of the maximal capacity, polymer chains cause an opening
of the occupied nanochannels, and because of the MOF reticular stiffness, this
opening is propagated to the neighboring nanochannels that become accessible for
adsorption. Composites were obtained by in situ polymerization of vinyl monomers
in the nanochannels of an otherwise nonporous MOF, resulting in homogeneously
loaded materials with a significant increase of porosity (SBET = 920 m2/g). In
addition, by limiting the accessible configurations for the framework and
forbidding the formation of a reactive intermediate, the polymeric guest
prevented the thermal degradation of the host MOF even at very low loading (as
low as 3 wt %) and increased its stability domain by more than 200 degrees C.
PMID- 28506066
TI - De Novo Computational Design for Development of a Peptide Ligand Oriented to
VEGFR-3 with High Affinity and Long Circulation.
AB - The overexpression of VEGFR-3 is correlated with a worse prognosis in lung cancer
and has been regarded as a rational target for specific drug delivery. Here,
VEGFR-3 homing peptide library was efficiently established by computational
design. Strong fluorescent signals of selected peptides were observed in A549
cells, but much weaker in other cells. The positive immunostaining overlapped
with VEGFR-3 confirmed high affinity and selectivity of one novel peptide (CP-7).
In addition, cell uptake of FITC-CP-7 peptide was significantly blocked by
coinjection of excess CP-7 peptide. After labeled with 131I, the profile of
pharmacology and biodistribution could be traced in vivo. The 131I-radiolabeled
CP-7 peptide conjugates were >85% stable in serum over 4 h and exhibited a
specific uptake of 18.04 +/- 2.04% ID/g at 0.5 h after injection to high VEGFR-3
expressing A549 tumor mice. More importantly, lower uptake concentration in heart
(1.06 +/- 0.15% ID/g) after 2 h demonstrated the safety of peptide in vivo. The
high uptake in the kidneys revealed that renal clearance was the main route of
131I-CP-7 peptide elimination from the body. Lower accumulation of 131I-CP-7
peptide in VEGFR-3 negative HeLa tumor mice further indicated that CP-7 peptide
exhibited a higher tumor-homing efficiency. These studies provided a
straightforward analytical access to design and screen bioactive peptide based on
protein structure and revealed that CP-7 peptide represented a promising homing
peptide of VEGFR-3-positive cancer in vitro and in vivo which could be used as a
novel target molecule to achieve efficient drug delivery.
PMID- 28506067
TI - PPh3 Mediated Reductive Annulation Reaction between Isatins and Electron
Deficient Dienes to Construct Spirooxindole Compounds.
AB - A PPh3 mediated reductive annulation reaction between isatins and 4,4-dicyano-2
methylenebut-3-enoates was developed. The reaction provided an alternative method
for constructing five- and three-membered all-carbon spirooxindole compounds.
Lithium chloride as a Lewis acid played a key role in the synthesis of
spirocyclopentenyl oxindole compounds.
PMID- 28506068
TI - Viologen-Based Conjugated Covalent Organic Networks via Zincke Reaction.
AB - Morphology influences the functionality of covalent organic networks and
determines potential applications. Here, we report for the first time the use of
Zincke reaction to fabricate, under either solvothermal or microwave conditions,
a viologen-linked covalent organic network in the form of hollow particles or
nanosheets. The synthesized materials are stable in acidic, neutral, and basic
aqueous solutions. Under basic conditions, the neutral network assumes radical
cationic character without decomposing or changing structure. Solvent polarity
and heating method determine product morphology. Depending upon solvent polarity,
the resulting polymeric network forms either uniform self-templated hollow
spheres (HS) or hollow tubes (HT). The spheres develop via an inside-out Ostwald
ripening mechanism. Interestingly, microwave conditions and certain solvent
polarities result in the formation of a robust covalent organic gel framework
(COGF) that is organized in nanosheets stacked several layers thick. In the gel
phase, the nanosheets are crystalline and form honeycomb lattices. The use of the
Zincke reaction has previously been limited to the synthesis of small viologen
molecules and conjugated viologen oligomers. Its application here expands the
repertoire of tools for the fabrication of covalent organic networks (which are
usually prepared by dynamic covalent chemistry) and for the synthesis of viologen
based materials. All three materials-HT, HS, and COGF-serve as efficient
adsorbents of iodine due to the presence of the cationic viologen linker and, in
the cases of HT and HS, permanent porosity.
PMID- 28506069
TI - Interplay between adsorbed peptide structure, trapped water, and surface
hydrophobicity.
AB - Atomistic molecular dynamics simulations were used to study the influence of
interfacial water on the orientation and conformation of a facewise amphipathic
alpha-helical peptide adsorbed to hydrophilic and hydrophobic substrates. Water
behavior beneath the peptide adsorbed to a hydrophilic surface was observed to
vary with the height of the peptide above the surface. In general, the
orientation of water close to the peptide (with the oxygen atom pointing up
toward the peptide) was complementary to that observed near the hydrophilic
surface in the absence of peptide. That is, no change in orientation of water
trapped between the peptide and a hydrophilic surface is required as the peptide
approaches the surface. The adsorption of the peptide to the hydrophilic surface
was observed to be mediated by a layer of ordered water. Water was found to be
largely excluded on adsorption to the hydrophobic surface. However, the small
amount of water present was observed to be highly ordered. At the closest point
of contact to the hydrophobic surface, the peptide was observed to make direct
contact. These findings shed light on the fundamental driving forces of peptide
adsorption to hydrophobic and hydrophilic surfaces in aqueous environments.
PMID- 28506070
TI - Hepatic hematoma after ERCP: two new case reports.
AB - ERCP is an endoscopic procedure with a complication risk ranging from 2.5 to 8%.
The most frequent complications are pancreatitis, cholangitis, hemorrhage or
perforation. Hepatic hematoma after ERCP is a potentially serious, rare
complication. Not many cases are reported in the literature. We present here two
new cases of hepatic hematoma following ERCP along with a review of the
literature and possible therapeutic options.
PMID- 28506071
TI - Fecal microbiota transplantation in recurrent Clostridium difficile infection in
a patient with concomitant inflammatory bowel disease.
AB - The use of fecal microbiota transplantation in recurrent Clostridium difficile
infection and coexistent inflammatory bowel disease remains unclear. A 61-year
old man with ulcerative pancolitis was diagnosed with a third recurrence of
Clostridium difficile infection, previously treated with metronidazole,
vancomycin and fidaxomicin. Fecal microbiota transplantation of an unrelated
healthy donor was performed by the lower route. After a twelve month follow-up,
the patient remains asymptomatic without Clostridium difficile infection relapses
or inflammatory bowel disease flare-ups. Fecal microbiota transplantation is
relatively simple to perform, well-tolerated, safe and effective in recurrent
Clostridium difficile infection with ulcerative pancolitis, as an alternative in
case of antibiotic therapy failure.
PMID- 28506074
TI - Primary peripancreatic lymph node tuberculosis as a differential diagnosis of
pancreatic neoplasia.
AB - Primary peripancreatic lymph node tuberculosis is an exceptional entity in
immunocompetent patients, but its incidence is increasing in developed countries
in recent years due to increasing immigration. It usually presents as a
pancreatic mass and is misdiagnosed as pancreatic neoplasia in most cases, with
the diagnosis of tuberculosis occurring after surgery. We report the case of a 38
year old Pakistani man with abdominal pain of several months duration, who was
initially diagnosed with a pancreatic neoplasm after detecting a mass in the
pancreatic isthmus by computed tomography (CT) and abdominal magnetic resonance
imaging (MRI). However, after performing an endoscopic ultrasound-guided fine
needle aspiration biopsy (EUS-FNAB), the patient was diagnosed with
peripancreatic lymph node tuberculosis. After receiving anti-tuberculous
treatment, the patient presented clinical improvement, despite a small reduction
in the lesion size. In conclusion, peripancreatic lymph node tuberculosis is part
of the differential diagnosis of pancreatic neoplasia. Endoscopic ultrasound
guided fine-needle aspiration biopsy (EUS-FNAB) represents a valuable and useful
diagnostic tool for detecting this pathology, avoiding surgeries with a high
morbidity and mortality.
PMID- 28506075
TI - Cardiovascular Effects of Continuous Positive Airway Pressure Treatment in
Patients With Obstructive Sleep Apnea: A Meta-Analysis.
AB - Continuous positive airway pressure (CPAP) is the first-line treatment of
obstructive sleep apnea (OSA). Obstructive sleep apnea is a predictor of
cardiovascular (CV) events. In this meta-analysis, we evaluated the effect of
CPAP on left ventricular ejection fraction (LVEF), CV events, CV mortality, and
all-cause mortality in patients with OSA. Nine articles (n = 9610 patients) were
analyzed. Four different meta-analyses were performed: evaluation of LVEF,
assessment of all-cause mortality, CV mortality, and CV events. Continuous
positive airway pressure treatment was associated with a significant increase in
LVEF (mean difference: 2.1%, 95% confidence interval [CI]: 0.8%-3.4%). There was
a nonsignificant reduction in all-cause mortality (hazard ratio [HR]: 0.92, 95%
CI: 0.73-1.15) but a significant reduction of 66% in the risk of CV mortality
associated with the CPAP treatment (HR: 0.34, 95% CI: 0.17-0.68, P = .002). There
was a nonsignificant reduction in the risk of CV events in the CPAP-treated
patients (HR: 0.84, 95% CI: 0.60-1.18, P = .31). Our meta-analyses showed that
CPAP treatment improves LVEF and could have a beneficial effect on CV mortality.
PMID- 28506076
TI - NOS2 as an Emergent Player in Progression of Cancer.
AB - Although the inducible form of nitric oxide synthase (NOS2) was initially shown
to be a major player as an antitumor component of the immune response, more
recent data have shown that NOS2 expression in cancer cells often predicts poor
outcome. Unlike growth factors associated with a single oncogenic pathway, nitric
oxide (NO) has a ubiquitous nature wherein it simultaneously mediates major
oncogenic pathways from Akt/PI3K and RAS/ERK to HIF1a and TGFb. These interactive
loops perpetuate oncogenic mechanism that leads to increased cancer stemness,
proliferation metastasis, chemoresistance, angiogenesis, and immunosuppression.
Examination of a wide variety of patient tumors demonstrates that NOS2 expression
is >50% for most cancers. In many cases, elevated NOS2 has been shown to predict
poor outcome in cancer such as ER- breast cancer, glioma, melanoma, cervical,
liver, ovarian, and pancreatic. Taken together, NOS2 may be one of the most
powerful biomarker and predictors of poor prognosis and an ideal target for
cancer therapy. Antioxid. Redox Signal. 26, 963-965.
PMID- 28506078
TI - 'My husband is possessed by a jinn': a case study in transcultural mental health.
AB - Objectives The objective of this study was to discuss jinn possession in Muslim
culture, and the importance of understanding cultural differences in mental
health. Conclusion It is important to understand cultural and religious
differences in psychiatry, as it affects the way patients perceive and attribute
symptoms. It also helps clinicians to reach an accurate diagnosis and provide
appropriate treatments. Beliefs about jinn possession should not automatically be
regarded as delusional. In alleged cases of jinn possession, clinicians should
consider all the biopsychosocial, cultural and spiritual factors that are unique
to the individual. Further research is still needed in this area.
PMID- 28506077
TI - Successful clozapine re-challenge following myocarditis.
AB - OBJECTIVE: To explore the evidence around clozapine re-challenge following
myocarditis. CONCLUSION: This case adds to the 17 cases of clozapine re-challenge
following myocarditis, of which 71% were successful (12 cases). This demonstrates
that re-challenge could be performed safely and effectively in the context of
clozapine-induced myocarditis, if accompanied by a strict and rigorous monitoring
protocol.
PMID- 28506080
TI - Hepatocellular carcinoma treatment: a comparative review of emerging growth
factor receptor antagonists.
AB - INTRODUCTION: Hepatocellular carcinoma (HCC) is a leading cause of death
worldwide. Over the last decade, sorafenib has been the only available
therapeutic option for advanced HCC, although regorafenib recently showed a
survival benefit compared with placebo in a second-line setting. Areas covered:
This review discusses key published and ongoing studies with targeted agents in
HCC, molecular targets of HCC, the mechanism of resistance to sorafenib, and the
role of biomarker-enriched clinical trials. Expert opinion: The multiplicity of
drivers and the existence of substantial molecular heterogeneity limit the
benefits of targeted therapies in HCC. Based on molecular biology developments, a
few biomarker-enriched clinical trials that target candidate driver genes are
ongoing, and the outcomes of these are highly anticipated. Poor availability of
tumor tissue and tumor heterogeneity in patients with HCC make liquid biopsy a
very attractive option, although this technique remains to be validated.
PMID- 28506079
TI - The Neural Correlates of Emotional Lability in Children with Autism Spectrum
Disorder.
AB - Autism spectrum disorder (ASD) is exceptionally heterogeneous in both clinical
and physiopathological presentations. Clinical variability applies to ASD
specific symptoms and frequent comorbid psychopathology such as emotional
lability (EL). To date, the physiopathological underpinnings of the co-occurrence
of EL and ASD are unknown. As a first step, we examined within-ASD inter
individual variability of EL and its neuronal correlates using resting-state
functional magnetic resonance imaging (R-fMRI). We analyzed R-fMRI data from 58
children diagnosed with ASD (5-12 years) in relation to the Conners' Parent
Rating Scale EL index. We performed both an a priori amygdala region-of-interest
(ROI) analysis, and a multivariate unbiased whole-brain data-driven approach.
While no significant brain-behavior relationships were identified regarding
amygdala intrinsic functional connectivity (iFC), multivariate whole-brain
analyses revealed an extended functional circuitry centered on two regions:
middle frontal gyrus (MFG) and posterior insula (PI). Follow-up parametric and
nonparametric ROI-analyses of these regions revealed relationships between EL and
MFG- and PI-iFC with default, salience, and visual networks suggesting that
higher-order cognitive and somatosensory processes are critical for emotion
regulation in ASD. We did not detect evidence of amygdala iFC underpinning EL in
ASD. However, exploratory whole-brain analyses identified large-scale networks
that have been previously reported abnormal in ASD. Future studies should
consider EL as a potential source of neuronal heterogeneity in ASD and focus on
multinetwork interactions.
PMID- 28506081
TI - Epidemiological characteristics of Chinese paediatric traumatic brain injury
inpatients.
AB - PRIMARY OBJECTIVE: To investigate the epidemiological characteristics of
paediatric inpatients with traumatic brain injury (TBI) in China. RESEARCH
DESIGN: The Chinese Trauma Database (CTD), a nationwide register system based on
hospital admission data, contains diagnosis and treatment information for trauma
inpatients in over 200 military-managed public-service hospitals in China. Using
the ICD-9 coding, the data for children with TBI aged 0-17 years between 2001 and
2007 were retrieved. METHODS AND PROCEDURES: The demographic characteristics,
admission time, injury cause, severity and treatment outcomes of paediatric
inpatients with TBI were analysed. MAIN OUTCOMES AND RESULTS: A total of 26,028
paediatric inpatients with TBI (69.52% male, 30.48% female) were included in the
CTD. Motor vehicle traffic (MVT) accidents, falls and assaults were the primary
causes of injury. Falls were the leading cause of TBI in children aged 0-4 years,
and MVT was the leading cause of TBI in children aged 5-17 years. According to
the abbreviated injury scale, 37.20% of the TBI cases were mild, 25.15% were
moderate, 24.81% were severe and 12.84% were critically severe. CONCLUSION:
Chinese authorities should develop targeted measures to reduce children injuries
based on the leading causes of TBI in the different age groups, particularly MVT,
falls and assaults.
PMID- 28506082
TI - Novel Use of Active Leptospermum Honey for Ringed Fixator Pin Site Care in
Diabetic Charcot Deformity Patients.
AB - INTRODUCTION: Open reduction with external fixation (OREF) utilizing fine wire
ringed fixators for correction of Charcot deformity has gained popularity over
the past decade. Pin site infections are a well-documented complication of
external fixation as well as a driver of escalating health care costs. We aimed
to demonstrate the safety and efficacy of a novel method of pin site care
utilizing active Leptospermum honey-impregnated dressings (MediHoney) in diabetic
patients undergoing deformity correction with OREF. METHODS: Twenty-one diabetic
patients with Charcot deformities of the lower extremity were prospectively
enrolled and followed for pin site complications following OREF for deformity
correction. Active Leptospermum honey dressings were applied at metal-cutaneous
interfaces at the end of the OREF procedure and replaced weekly for a total of 8
weeks. Patients were monitored for pin site infections from the time of surgery
until external fixator removal. Sixteen consecutive patients receiving standard
OREF for Charcot deformities were evaluated retrospectively to serve as a control
group. RESULTS: Of the 21 enrolled patients, 19 underwent OREF and followed up
throughout the study period. Treated patients had a mean age of 58.5 years and
mean body mass index measuring 33.3 kg/m2 as documented prior to surgery. The 15
patients with hemoglobin A1c labs drawn in the 3 months preceding surgery
averaged 7.5. Fixators were removed at an average of 12.1 weeks after adequate
bony healing. Of the 244 pin sites in 19 patients, 3 pin sites (1.2% of pins) in
2 patients (10.5% of patients) showed evidence of superficial infection. All
infections resolved with oral antibiotics. Infection rates were significantly
reduced when compared to the standard care control group. CONCLUSIONS: Pilot data
in a prospectively collected case series demonstrate safety and efficacy of
active Leptospermum honey-impregnated dressings when used for fine wire ringed
fixator pin site care in diabetic Charcot deformity patients. Further
investigation in the form of a prospective randomized controlled study is
warranted to demonstrate the potential value of this novel intervention. LEVELS
OF EVIDENCE: Level IV.
PMID- 28506083
TI - Ultrasound-Guided Percutaneous Needle Fenestration and Corticosteroid Injection
for Anterior and Anterolateral Ankle Impingement.
AB - BACKGROUND: Ankle impingement is a common cause of chronic ankle pain. We
retrospectively studied the effectiveness of ultrasound-guided percutaneous
needle fenestration of the pathological soft tissues combined with corticosteroid
injection to treat this condition. METHODS: We administered a telephone survey to
patients who underwent the procedure. Patients were asked questions on the Foot
Function Index and queried about their overall satisfaction with the procedure on
a scale of 0 (completely unsatisfied) to 10 (very satisfied). RESULTS: Forty-nine
patients participated in the survey: 26 women and 23 men, mean age 42.7 years
(range, 19-65 years). Impingement was anterior in 26/49 (53.1%), anterolateral in
14/49 (28.6%), and both in 9/49 (18.4%). Mean pain level before the procedure was
6.76 +/- 1.84 and after the procedure was 2.73 +/- 2.21. Reported pain scale
levels declined by 4.02 +/- 2 units after the procedure (P < .0001). Patient's
overall satisfaction was 7.9 +/- 2.44. CONCLUSIONS: Ultrasound-guided
percutaneous needle fenestration and corticosteroid injection appears to be an
effective nonoperative alternative for treatment of anterior and/or anterolateral
ankle impingement. LEVELS OF EVIDENCE: Level IV.
PMID- 28506084
TI - Turmeric: old spice, new spice.
AB - The history of chemical investigations into the yellow components of turmeric can
be traced from 1815. Although the major yellow component of turmeric, curcumin,
often is represented as a 1,3-diketone in the solid state and in nonaqueous
solution, it exists in the enol form. The struggle to identify the chemical
structure of curcumin continued for nearly a century and was complicated by the
difficult purification of curcumin and by the presence of two additional yellow
components. Food remains the main use for turmeric (old spice); its use as a dye
has diminished since the 19th century, but it may have pharmaceutical uses (new
spice).
PMID- 28506085
TI - Long-term exposure to a continuous 900 MHz electromagnetic field disrupts
cerebellar morphology in young adult male rats.
AB - The pathological effects of exposure to an electromagnetic field (EMF) during
childhood and adolescence may be greater than those from exposure during
adulthood. We investigated possible pathological changes in the cerebellum of
adolescent rats exposed to 900 MHz EMF daily for 25 days. We used three groups of
six 21-day-old male rats as follows: unexposed control group (Non-EG), sham
exposed group (Sham-EG) and an EMF-exposed group (EMF-EG). EMF-EG rats were
exposed to EMF in an EMF cage for 1 h daily from postnatal days 21 through 46.
Sham-EG rats were placed in the EMF cage for 1 h daily, but were not subjected to
EMF. No procedures were performed on the Non-EG rats. The cerebellums of all
animals were removed on postnatal day 47, sectioned and stained with cresyl
violet for histopathological and stereological analyses. We found significantly
fewer Purkinje cells in the EMF-EG group than in the Non-EG and Sham-EG groups.
Histopathological evaluation revealed alteration of normal Purkinje cell
arrangement and pathological changes including intense staining of neuron
cytoplasm in the EMF-EG group. We found that exposure to continuous 900 MHz EMF
for 1 h/day during adolescence can disrupt cerebellar morphology and reduce the
number of Purkinje cells in adolescent rats.
PMID- 28506086
TI - Invasive cardiopulmonary exercise testing in the evaluation of unexplained
dyspnea: Insights from a multidisciplinary dyspnea center.
AB - Background Unexplained dyspnea is a common diagnosis that often results in
repeated diagnostic testing and even delayed treatments while a determination of
the cause is being investigated. Through a retrospective study, we evaluated the
diagnostic efficacy of a multidisciplinary dyspnea evaluation center (MDEC) using
invasive cardiopulmonary exercise test to diagnose potential causes of
unexplained dyspnea. Methods We reviewed the medical records of all patients
referred with unexplained dyspnea to the MDEC between March 2011 and October
2014. We assessed the diagnostic efficacy before and after presentation to the
MDEC. Results During the study period a total of 864 patients were referred to
the MDEC and, of those, 530 patients underwent further investigation with
invasive cardiopulmonary exercise test and constituted the study sample. The
median age was 57 (44-68) years, 67.2% were women, and median body mass index was
26.22 (22.78-31.01). A diagnosis was made in 530 patients including: exercise
pulmonary arterial hypertension of 88 (16.6%), heart failure with preserved
ejection fraction of 94 (17.7%), dysautonomia 112 (21.1%), oxidative myopathy of
130 (24.5%), primary hyperventilation of 43 (8.1%), and other 58 (10.9%). The
time from initial presentation to referral was significantly longer than time to
diagnosis after referral for non-standardized conventional methods versus
diagnosis through MDEC using invasive cardiopulmonary exercise test (511 days
(292-1095 days) vs. 27 days (13-53 days), p < 0.0001). In a subgroup analysis, we
reviewed that patients referred from cardiovascular clinics were more likely to
have a greater number of diagnostic tests performed and, conversely, patients
referred from pulmonary clinics were more likely to have a greater number of
treatments prescribed before referral to MDEC. Conclusions As a result of this
retrospective study, we have evaluated that a multidisciplinary approach that
includes invasive cardiopulmonary exercise test dramatically reduces the time to
diagnosis compared with traditional treatment and testing methods.
PMID- 28506087
TI - Differential variations of autophagy and apoptosis in permanent focal cerebral
ischaemia rat model.
AB - OBJECTIVE: Autophagy and apoptosis coexist in stroke, but the relationship
between effects and complex is poorly understood. Herein, we investigated dynamic
changes of autophagy and apoptosis at the penumbra in permanent cerebral
ischaemia. METHODS: Sprague-Dawley rat models were prepared by middle cerebral
artery occlusion. The autophagy and apoptosis were evaluated by Western blotting
and immunofluorescence with LC3-II and cleaved caspase-3, respectively. The
neurological deficit score and infarct volume were assessed. RESULTS: The results
showed that the expressions of LC3-II and cleaved caspase-3 were gradually
increased from 1 to 5 hours, and reached maximum at 5 hours after stroke. After
that, LC3-II expression was significantly declined, but cleaved caspase-3
expression was only mildly reduced from 6 hours to 3 days. Surprisingly, at 4
days after stroke, the autophagy was abruptly increased again, but the apoptosis
was considerably and continuously decreased. The severity of the neurological
deficit was in accordance with the increase of infarct expansion. CONCLUSIONS:
Our results showed that autophagy and apoptosis were simultaneously activated
within 12 hours after stroke. Four days later, LC3-II expression was
significantly increased, while cleaved caspase-3 expression was considerably
decreased, implying that there might be a transition from apoptosis to autophagy
at the subacute phase of stroke.
PMID- 28506088
TI - Trends in white blood cell and platelet indices in a comparison of patients with
papillary thyroid carcinoma and multinodular goiter do not permit differentiation
between the conditions.
AB - AIM: Carcinogenesis has been related to systematic inflammatory response. Our aim
was to study white blood cell and platelet indices as markers of this
inflammatory response in thyroid cancer and to associate them with various
clinicopathological parameters. METHODS: We included 228 patients who underwent
thyroidectomy within a period of 54 months, 89 with papillary thyroid carcinoma
and 139 with multinodular hyperplasia. We examined potential links between white
blood cell and platelet indices on the one hand and the type thyroid pathology
and various clinicopathological parameters on the other. RESULTS: No significant
differences were detected between thyroid cancer and multinodular hyperplasia and
no significant associations were detected with regard to lymphovascular invasion
and tumor size. However, the mean platelet volume was higher in multifocal
tumors, while the platelet count, plateletcrit, and platelet-to-lymphocyte ratio
were increased in cases with extrathyroidal extension and in T3 tumors.
Additionally, T3 tumors had lower platelet distribution width. These associations
demonstrated low accuracy in predicting these pathological features, but they
were found to provide a satisfying negative predictive value, with the exception
of the mean platelet volume. CONCLUSIONS: White blood cell and platelet indices
cannot assist in distinguishing benign goiter from thyroid cancer. However, they
can provide information about tumor multifocality, extrathyroidal extension, and
presence of a T3 tumor, and they may be used as a means to exclude these
pathological characteristics, especially the last two, in papillary thyroid
carcinoma.
PMID- 28506089
TI - Long-Term Oxygen Therapy in COPD Patients Who Do Not Meet the Actual
Recommendations.
AB - Chronic respiratory failure due to chronic obstructive pulmonary disease (COPD)
is an increasing problem worldwide. Many patients with severe COPD develop
hypoxemic respiratory failure during the natural progression of disease. Long
term oxygen therapy (LTOT) is a well-established supportive treatment for COPD
and has been shown to improve survival in patients who develop chronic hypoxemic
respiratory failure. The degree of hypoxemia is severe when partial pressure of
oxygen in arterial blood (PaO2) is <=55 mmHg and moderate if PaO2 is between 56
and 69 mmHg. Although current guidelines consider LTOT only in patients with
severe resting hypoxemia, many COPD patients with moderate to severe disease
experience moderate hypoxemia at rest or during special circumstances, such as
while sleeping or exercising. The efficacy of LTOT in these patients who do not
meet the actual recommendations is still a matter of debate, and extensive
research is still ongoing to understand the possible benefits of LTOT for
survival and/or functional outcomes such as the sensation of dyspnea,
exacerbation frequency, hospitalizations, exercise capacity, and quality of life.
Despite its frequent use, the administration of "palliative" oxygen does not seem
to improve dyspnea except for delivery with high-flow humidified oxygen. This
narrative review will focus on current evidence for the effects of LTOT in the
presence of moderate hypoxemia at rest, during sleep, or during exercise in COPD.
PMID- 28506091
TI - Reaching the Unreachable: Novel Approaches to Telemedicine Screening of
Underserved Populations for Vitreoretinal Disease.
AB - Telemedicine involves electronic communication between a physician in one
location and a patient in another location to provide remote medical care.
Ophthalmologists are increasingly employing telemedicine, particularly in retinal
disease screening and monitoring. Telemedicine has been utilized to decrease
barriers to care and yield greater patient satisfaction and lower costs, while
maintaining high sensitivity and specificity. This review discusses common
patient barriers to eye care, innovative approaches to retinal disease screening
and monitoring using telemedicine, and eye care policy initiatives needed to
enact large-scale telemedicine eye disease screening programs.
PMID- 28506093
TI - The Virtual Short Physical Performance Battery: Psychometric Properties and
Validation in Older Adults With Multiple Sclerosis.
AB - BACKGROUND: There are increasing numbers of older adults with multiple sclerosis
(MS) who undergo declines in physical function that require attention of
clinicians and researchers. Objective and perceived measures of disablement
feasible for clinical and residential settings, such as the Short Physical
Performance Battery and its virtual counterpart (vSPPB), are critical for
defining the degree of disablement. OBJECTIVE: We evaluated the psychometric
properties and validity of the vSPPB as a measure of perceived lower extremity
physical function in older adults with MS (age >=60 years). METHOD: The sample
included 35 older adults with MS and 35 age- and sex-matched healthy controls
(age >=60 years) who completed a battery of assessments, including the vSPPB.
RESULTS: The vSPPB performed satisfactorily in older adults with MS regarding
data quality, scaling assumptions, and acceptability (i.e., psychometrics). The
vSPPB further demonstrated criterion, known-groups, convergent, and discriminant
construct validity. CONCLUSION: This report provides evidence for the validity of
vSPPB scores as a measure of perceived lower extremity physical function in older
adults with MS.
PMID- 28506092
TI - Variants of the ADRB2 Gene in COPD: Systematic Review and Meta-Analyses of
Disease Risk and Treatment Response.
AB - The beta2-adrenergic receptor (ADRB2) is an important regulator of airway smooth
muscle tone in chronic obstructive pulmonary disease (COPD). Variants that impair
ADRB2 function could increase disease risk or reduce the response to endogenous
and inhaled adrenergic agonists in COPD. We performed a systematic review and
three meta-analyses to assess whether three functional variants (Thr164Ile,
Arg16Gly, and Gln27Glu) in the ADRB2 gene are associated with elevated risk of
disease or reduced therapeutic response to inhaled beta2-agonists in COPD. We
searched the medical literature from 1966 to 2017 and found 16 relevant studies
comprising 85381 study subjects. The meta-analyses found no significant
association between ADRB2 genotype and COPD risk. The summary odds ratios (ORs)
for COPD in Thr164Ile homozygotes and heterozygotes were 2.57 (95% confidence
interval (CI): 0.54-12.4) and 1.17 (95% CI: 0.96-1.44), respectively.
Corresponding summary ORs for COPD in Arg16Gly homozygotes and heterozygotes were
0.97 (95% CI: 0.76-1.22) and 1.01 (95% CI: 0.81-1.26), while summary ORs for COPD
in Gln27Glu homozygotes and heterozygotes were 1.00 (95% CI: 0.80-1.25) and 0.94
(95% CI: 0.69-1.24), respectively. When stratified by ethnicity, the summary ORs
for COPD did not differ from 1.0 for any of the ADRB2 variants among Asian,
Caucasian, or African populations. We found no consistent associations between
ADRB2 genotype and treatment response to inhaled beta2-agonists in COPD. This
systematic review and meta-analyses found that COPD risk and response to inhaled
beta2-agonists were not associated with Thr164Ile, Arg16Gly, and Gln27Glu
genotypes. However, identified cases of Thr164Ile were few, and additional
studies of rare ADRB2 genotypes are required.
PMID- 28506094
TI - A preliminary study of youth sport concussions: Parents' health literacy and
knowledge of return-to-play protocol criteria.
AB - PRIMARY OBJECTIVE: To preliminarily explore parents' health literacy and
knowledge of youth sport league rules involving concussion education and
training, and return-to-play protocols. RESEARCH DESIGN AND METHODS: This study
was guided by the Knowledge, Attitude and Practice (KAP) model of health
knowledge to examine parents' concussion literacy, and understanding of
concussion education and training, and return-to-play protocols in youth sports.
The mixed-method design involved 119 participants; that included in-person (n=8)
and telephone (n=4) interviews, and web-based surveys administered through
Mechanical Turk via Qualtrics (n=98). MAIN OUTCOMES AND RESULTS: Most respondents
were not familiar with concussion protocols, but trusted coaches' knowledge in
return-to-play rules. More than half of the respondents report that the return-to
play concussion criteria have not been clearly explained to them. The majority of
respondents were not familiar with the CDC's 'Heads Up' online concussion
training programme, nor were they familiar with any other educational/training
tool. About one-fifth of the parents had conversations with a coach or medical
staff about youth sport concussions. CONCLUSION: Parents have a general
understanding of how to identify concussion symptoms, but lack knowledge of
immediate steps to take following an incident other than seeking medical help.
PMID- 28506090
TI - Rational design strategies for FimH antagonists: new drugs on the horizon for
urinary tract infection and Crohn's disease.
AB - INTRODUCTION: The bacterial adhesin FimH is a virulence factor and an attractive
therapeutic target for urinary tract infection (UTI) and Crohn's Disease (CD).
Located on type 1 pili of uropathogenic E. coli (UPEC), the FimH adhesin plays an
integral role in the pathogenesis of UPEC. Recent efforts have culminated in the
development of small-molecule mannoside FimH antagonists that target the mannose
binding lectin domain of FimH, inhibiting its function and preventing UPEC from
binding mannosylated host cells in the bladder, thereby circumventing infection.
Areas covered: The authors describe the structure-guided design of mannoside
ligands, and review the structural biology of the FimH lectin domain.
Additionally, they discuss the lead optimization of mannosides for therapeutic
application in UTI and CD, and describe various assays used to measure mannoside
potency in vitro and mouse models used to determine efficacy in vivo. Expert
opinion: To date, mannoside optimization has led to a diverse set of small
molecule FimH antagonists with oral bioavailability. With clinical trials already
initiated in CD and on the horizon for UTI, it is the authors, opinion that
mannosides will be a 'first-in-class' treatment strategy for UTI and CD, and will
pave the way for treatment of other Gram-negative bacterial infections.
PMID- 28506095
TI - Understanding attitudes toward information and communication technology in home
care: Information and communication technology as a market good within Norwegian
welfare services.
AB - The aim of this study was to better understand nurses' and other staff members'
attitudes toward the usefulness of information and communication technology in
home-care settings. Research has found that beliefs about the expected benefits
of information and communication technology impact the use of technology.
Furthermore, inexperience with using information and communication technology may
cause negative attitudes. This article is based on a questionnaire to 155 nurses
and other staff members in home-care in Sogn og Fjordane county in Norway. The
results revealed minimal use of information and communication technology at work;
however, participants had positive attitudes regarding the potential benefits of
information and communication technology use in home-care. Individuals' extensive
use of and familiarity with different solutions in private lives could be an
important context for explaining employees' attitudes. Given that information and
communication technology is both a welfare service and a market good, this may
explain individuals' positive attitudes toward information and communication
technology despite their lack of experience with it at work. Experiences with
information and communication technology as a market good and the way new
technologies can affect work routines will affect the implementation of
information and communication technology in home-care.
PMID- 28506096
TI - Response to: The cost of caring.
PMID- 28506097
TI - A computational model of the [Formula: see text] transients and influence of
buffering in guinea pig urinary bladder smooth muscle cells.
AB - Many cellular events including electrical activity and muscle contraction are
regulated and coordinated by intracellular [Formula: see text] concentration
([[Formula: see text]][Formula: see text]. In detrusor smooth muscle (DSM) cells,
[[Formula: see text]]i is normally maintained at very low levels and rises
transiently during signalling processes as a result of (i) influx from the
extracellular space (mainly via L-type and T-type [Formula: see text] channels)
and (ii) [Formula: see text] release from sarcoplasmic reticulum (SR) into the
cytoplasm. Intracellular [Formula: see text] buffers, both fixed and diffusible,
play a vital role in shaping the radial distribution of free [Formula: see text].
Our aim, in the work presented here, is to develop a mathematical model of
[Formula: see text] buffering and diffusion and to generate [Formula: see text]
transient in guinea pig DSM cells. The [Formula: see text] transient is generated
using inward [Formula: see text] current that arises following voltage clamp and
mediated by L-type and T-type [Formula: see text] channels. [Formula: see text]
transient is obtained for different radial locations (or shells) of the DSM
cytosol. This modeling study explores the levels of [[Formula: see text]]i
achieved near the plasma membrane and in deeper locations. The [Formula: see
text] transient generated in our model shows a high degree of similarity with
experimental findings in terms of amplitude, duration and half-decay time. A
number of different buffer properties such as concentration and mobility are
tested for their effect on amplitude and shape of [Formula: see text] transient.
The presence of fast buffer concentration in the cytosol markedly delays the rise
of [[Formula: see text]]i in the core of the cell. Increase in the mobility of
fast buffer slightly speeds up the redistribution of [Formula: see text]. To
explore the model further, the role of plasma membrane [Formula: see text]-ATPase
(PMCA) pump, sarcoplasmic/endoplasmic reticulum [Formula: see text]-ATPase
(SERCA) pump and sodium calcium exchanger (NCX) on [Formula: see text] transient
is studied and it is suggested that NCX may be of primary importance for the
immediate lowering of [[Formula: see text]]i during the falling phase of a
[Formula: see text] transient in DSM cells.
PMID- 28506098
TI - Long-term influence of sialoadenectomy on the liver of male albino rat.
AB - Epidermal growth factor is an endocrine product of the submandibular gland; the
liver is an important target of its action and is affected by sialoadenectomy.
Thirty rats were used in this study and divided into group I (sham-operated
animals), group II (sialoadenectomy after 4 weeks), and group III
(sialoadenectomy after 10 weeks). Liver samples were processed for light and
electron microscope examination. Sialoadenectomy induced mild-to-moderate liver
damage which persists up to 10 weeks after the operation. This damage is
manifested morphologically rather than functionally, affecting the general
structure, hepatocytes, hepatic stellate cells, and hepatic sinusoids.
PMID- 28506099
TI - Propofol-Based Palliative Sedation to Treat Antipsychotic-Resistant Agitated
Delirium.
AB - Delirium is a common problem in terminally ill patients that is associated with
significant distress and, hence, considered a palliative care emergency. The
three subtypes of delirium are hyperactive, hypoactive, and mixed, depending on
the level of psychomotor activity and arousal disturbance. When agitated delirium
becomes refractory in the setting of imminent dying, the agitation may be so
severe that palliative sedation (PS) is required. Palliative sedation involves
the administration of sedative medications with the purpose of reducing level of
consciousness for patients with refractory suffering in the setting of a terminal
illness. Propofol is a sedative that has a short duration of action and a very
rapid onset. These characteristics make it relatively easy to titrate. Reported
doses range from 50 to 70 mg per hour. The authors present a case of
antipsychotic-resistant agitated delirium treated with a propofol intravenous
infusion.
PMID- 28506100
TI - Diagnostic performance of CTLA-4, carcinoembryonic antigen and CYFRA 21-1 for
malignant pleural effusion.
AB - OBJECTIVES: The diagnosis of malignant pleural effusion (MPE) remains a clinical
challenge. As a negative regulator of T-cell activation, cytotoxic T lymphocyte
associated antigen-4 (CTLA-4) has been associated with many malignant diseases.
However, there is limited data about the relationship between CTLA-4 and MPE. The
present study aims to investigate whether CTLA-4 levels may correlate with
presence of MPE and to assess its potential diagnostic accuracy relative to that
of the established markers carcinoembryonic antigen (CEA) and cytokeratin 19
fragment (CYFRA21-1). METHODS: Pleural effusion samples were collected from 36
patients with MPE and 48 patients with benign pleural effusion (BPE). Pleural
levels of CTLA-4 were measured by ELISA; levels of CEA and CYFRA 21-1, by
electrochemiluminescence immunoassay. Receiver operating characteristic curves
were calculated to evaluate the ability of CTLA-4, CEA and CYFRA 21-1 to
differentiate MPE from BPE. RESULTS: Pleural levels of CTLA-4 were significantly
higher in MPE than in BPE patients (471.73 +/- 378.86 vs. 289.22 +/- 173.67
pg/ml, p = 0.004). At a cut-off value of 351.25 pg/ml, the sensitivity and
specificity of CTLA-4 in diagnosing MPE were 58.30% and 83.30%, respectively, and
the area under the curve was 0.72. Pleural levels of CEA and CYFRA 21-1 were also
higher in MPE. Using the combination of CTLA-4, CEA and CYFRA 21-1 increased
diagnostic sensitivity to 88.89% and the area under the curve to 0.92.
CONCLUSION: The results of this preliminary study suggest that increased levels
of CTLA-4 correlate with MPE, and that CTLA-4 may have some diagnostic usefulness
when used in combination with conventional tumor markers such as CEA and CYFRA 21
1. These results justify larger, more rigorous studies to validate our findings.
PMID- 28506102
TI - Reappraising the Impact of Offending on Victimization: A Propensity Score
Matching Approach.
AB - Existing evidence clearly supports an empirical connection between offending and
victimization. Often called the "victim-offender overlap," this relationship
holds for both sexes, across the life course, and across a wide range of
countries and cultural environments. In addition, the relationship is sustained
regardless of the study sample and statistical methods applied in the analyses of
the sample data. However, there has yet to be a study that examines this
relationship for violent and property crime using quasi-experimental methods
accounting for a wide range of potential confounders including individual
differences and cultural contexts. This study subjects the victim-offender
relationship to testing through propensity score matching for both violent and
property crimes using an international dataset. The results show that previous
violent and theft offending increases the odds of victimization when matching on
individual and contextual factors. This finding supports previous literature and
suggests that delinquent behavior may act as a "switch" that exposes one to
subsequent violent and theft victimization.
PMID- 28506101
TI - Evaluation of personal inhalable aerosol samplers with different filters for use
during anthrax responses.
AB - Risk of inhalation exposure to viable Bacillus anthracis (B. anthracis) spores
has primarily been assessed using short-term, stationary sampling methods which
may not accurately characterize the concentration of inhalable-sized spores
reaching a person's breathing zone. While a variety of aerosol sampling methods
have been utilized during previous anthrax responses, no consensus has yet been
established for personal air sampling. The goal of this study was to determine
the best sampler-filter combination(s) for the collection and extraction of B.
anthracis spores. The study was designed to (1) evaluate the performance of four
filter types (one mixed cellulose ester, MCE (pore size = 3 um), two
polytetrafluoroethylene, PTFE (1 and 3 um), and one polycarbonate, PC (3 um));
and (2) evaluate the best performing filters in two commercially available
inhalable aerosol samplers (IOM and Button). Bacillus thuringiensis kurstaki
[Bt(k)], a simulant for B. anthracis, served as the aerosol challenge. The
filters were assessed based on criteria such as ability to maintain low pressure
drop over an extended sampling period, filter integrity under various
environmental conditions, spore collection and extraction efficiencies, ease of
loading and unloading the filters into the samplers, cost, and availability.
Three of the four tested collection filters-except MCE-were found suitable for
efficient collection and recovery of Bt(k) spores sampled from dry and humid as
well as dusty and clean air environments for up to 8 hr. The PC (3 um) filter was
identified as the best performing filter in this study. The PTFE (3 um)
demonstrated a comparable performance, but it is more expensive. Slightly higher
concentrations were measured with the IOM inhalable sampler which is the
preferred sampler's performance criterion when detecting a highly pathogenic
agent with no established "safe" inhalation exposure level. Additional studies
are needed to address the effects of environmental conditions and spore
concentration. The data obtained in this investigation are crucial for future
efforts on the development and optimization of a method for assessing inhalation
exposure to B. anthracis.
PMID- 28506103
TI - Treatment-Seeking Behaviors of Persons With Rheumatoid Arthritis.
AB - PURPOSE: Describe perceptions of patients with rheumatoid arthritis (RA)
regarding disease-related pain, tendency to tell others about their pain, and
treatments used since diagnosis. DESIGN: Cross sectional, exploratory. METHOD: A
total of 63 participants responded to telephone interview about their treatments
and tendency to tell others about their RA pain. They also responded to McGill
Pain Questionnaire and Health Assessment Questionnaire (HAQ) items. Participants
marked pain location on mailed body outlines. FINDINGS: RA diagnosis occurred an
average of 11 years prior. Mean HAQ Standard Disability Index score was 1.26.
Previous week symptoms were joint pain (97%), joint swelling (83%), decreased
movement/function (83%), fatigue (70%), muscle weakness (65%). Mean morning
stiffness duration was 120 +/- 137 minutes. Mean pain intensity was 1.15 +/- 0.6
at its least and 3.8 +/- 1.1 at its worst. 65% were not satisfied with pain
levels. 57% stated a tendency not to tell others about their pain; 43% tended to
tell. 78% used medications and alternative therapies, none solely used
alternative therapies, and 22% only used medications. CONCLUSIONS: RA patients
reported high rates of alternative therapy use. Dissatisfaction with pain levels
indicates need for improved pain management. Not talking about pain lends
insights into the importance of teaching patients to communicate their pain to
others.
PMID- 28506104
TI - Application of weak ultrasonic treatment on sludge electro-osmosis dewatering.
AB - Ultrasonic treatment is a good method of facilitating sewage sludge dewatering
characteristics. It can also promote the potential of sludge electro-osmosis
dewatering (EDW), which is an accepted method of deep dewatering, but the
treatment method and optimizing conditions should be determined by performing
experiments. In this study, we consider two treating methods: ultrasonic pre
treatment, which uses ultrasonic treatment as sludge pre-treatment before electro
osmosis dehydration, and ultrasonic coupling, which uses ultrasonic and electric
fields simultaneously. Using sludge from the Tianjin Jizhuangzi sewage treatment
plant, we analyze the influence of ultrasonic intensity and treatment time on
sludge dewatering by performing two different methods. The results show that they
effectively facilitated sludge EDW. Under the same conditions, i.e. 2 cm cake
initial thickness, voltage of 60 V for 5 min, and 0.1 MPa mechanical pressure for
5.5 min, the optimum processing conditions for ultrasonic pre-treatment were
found to be 0.510 W/cm2 and 3.5 min, the dehydration rate reached 34.71%, and the
optimum conditions for ultrasonic coupling were 0.255 W/cm2 and 3.5 min, while
the dehydration rate reached 40.78%. The dehydration rates for both approaches
were clearly better than 17.40%, which was obtained under pure electro-osmosis
dehydration. To compare the effects of ultrasonic pre-treatment and ultrasonic
coupling on the electro-osmosis dehydration process, in this paper, we present
the curves of dehydration rate, electric current, electro-osmosis flow, and
scanning electron microscopy for dewatered sludge. Compared with the ultrasonic
pre-treatment method, the effect of ultrasonic coupling on electro-osmosis
dehydration was more obvious.
PMID- 28506105
TI - Evaluating the Types of Pharmacy Student Interventions Made During an
Interprofessional 6-Week Adult Internal Medicine Rotation.
AB - INTRODUCTION: The new standards for pharmacy education require that pharmacy
students are involved in direct and interprofessional team-based care in multiple
practice settings, which include "real-time" interactions with physician
prescribers and medical students. METHODS: From April 2014 to December 2015,
fourth-year Doctor of Pharmacy (PharmD) students at University Medical Center of
El Paso, Texas were assigned to an interprofessional team that was comprised of
physician prescribers, medical students, and a pharmacist faculty. They recorded
their interventions that were analyzed for type, number, physician acceptance,
clinical importance, and time requirements for intervention recommendation.
Interventions were divided into 5 main types and further divided into specific
categories. RESULTS: Twelve PharmD students contributed 531 interventions,
resulting in an average of 44 interventions per student with a physician
acceptance rate of 87%. The most common types of interventions performed by
PharmD students were under the categories of Therapy Needed (29.8%), Too Low
Dose/Frequency (21.1%), Too High Dose/Frequency (8.3%), Therapeutic Level
Monitoring (6.8%), and IV to PO Conversion (4.9%). A majority of interventions
were of moderate clinical importance (56.1%) and took approximately 15 minutes to
complete (92.5%). CONCLUSION: PharmD students under the supervision of clinical
faculty on an interprofessional internal medicine team are valuable collaborators
and contributors in decreasing the number of drug-related problems that can
negatively impact patient care.
PMID- 28506106
TI - Management of Direct-Acting Oral Anticoagulants Surrounding Dental Procedures
With Low-to-Moderate Risk of Bleeding.
AB - The purpose of this article is to review the available evidence regarding how to
safely manage direct-acting oral anticoagulant (DOAC) therapy in patients
requiring dental procedures with low-to-moderate risk of bleeding. A literature
search was performed using MEDLINE and PubMed. Each author performed an
independent search to ensure all pertinent articles were identified. The
reference sections of each article were also reviewed. Pertinent articles were
evaluated by each author for inclusion. Articles were eligible for inclusion if
the participants were taking DOAC therapy surrounding a dental procedure known to
have low-to-moderate risk of bleeding. Studies could be prospective or
retrospective and included case reports, case series, and clinical trials.
Articles were excluded if they assessed dental procedures known to carry a high
risk of bleeding or were review articles. Twenty-five articles were identified, 5
of which met inclusion criteria including 2 case series, 1 retrospective study,
and 2 prospective trials. Variation in the management of DOAC therapy surrounding
these procedures was found. Among patients undergoing low-to-moderate risk dental
procedures while receiving DOAC therapy, bleeding rates were low regardless of
whether the DOAC was held or continued surrounding the procedure. Documented
bleeding was mild and easily controlled by local hemostatic measures. Patients
can safely continue DOAC therapy surrounding these dental procedures.
PMID- 28506107
TI - Immunoassay approach for diagnosis of exposure to pyrrolizidine alkaloids.
AB - Numerous pyrrolizidine alkaloid (PA) poisoning cases have been documented
worldwide. Protein covalent binding with reactive metabolites generated from
metabolic activation of PAs to form pyrrole-protein adducts is suggested to be a
primary mechanism of PA-induced toxicities. The present study aimed to develop
antibodies for diagnosis of PA exposure. Polyclonal antibodies were raised in
rabbits and proven to specifically recognize pyrrole-protein adducts regardless
of amino acid residues modified by the reactive metabolites of PAs. The developed
antibodies were successfully applied to detect pyrrole-protein adducts in blood
samples obtained from PA-treated rats and exhibited a potential for the clinical
diagnosis of PA exposure.
PMID- 28506108
TI - Age differences in self-set goal effects for memory.
AB - Research has shown that goal setting leads to gains in memory performance and
memory self-efficacy across adulthood when goals are set by experimenters and
accompanied by positive feedback. However, self-set memory goals have had less
consistent impact. This research extended past studies on aging and memory goals
to examine the impact of self-set goals using anchors to guide goal selection.
Two trials of name, text, and list recall were administered to younger and older
adults, comparing goal and no-goal groups. After baseline, participants assigned
to the goal group set personal goals for memory gain on a second, post-goal trial
for each of the three tasks. Anchoring for goal-setting was used to encourage the
selection of realistic, yet challenging goals. Younger and older participants set
comparable goals. Only younger adults showed a motivational response (higher
gains across trials for goals than no goals), even though older adults reported
being just as committed to their personal goals. Older adults may have failed to
show reliable goal-related gains because no positive feedback was offered or
because they were unable to activate effective strategies for improved
performance.
PMID- 28506109
TI - Forgiveness, Attachment to God, and Mental Health Outcomes in Older U.S. Adults:
A Longitudinal Study.
AB - We analyze a sample of older U.S. adults with religious backgrounds in order to
examine the relationships among two types of divine forgiveness and three
indicators of psychological well-being (PWB) as well as the moderating role of
attachment to God. Results suggest that (a) feeling forgiven by God and
transactional forgiveness from God are not associated with changes in PWB over
time, (b) secure attachment to God at baseline is associated with increased
optimism and self-esteem, (c) feeling forgiven by God and transactional
forgiveness from God are more strongly associated with increased PWB among the
securely attached, and (d) among the avoidantly attached, PWB is associated with
consistency in one's beliefs, that is, a decreased emphasis on forgiveness from
God. Findings underscore the importance of subjective beliefs about God in the
lives of many older adults in the United States.
PMID- 28506110
TI - Evaluation of chemical mutagenicity using next generation sequencing: A review.
AB - Mutations are heritable changes in the nucleotide sequence of DNA that can lead
to many adverse effects. Genotoxicity assays have been used to identify chemical
mutagenicity. Recently, next generation sequencing (NGS) has been used for this
purpose. In this review, we present the progress in NGS application for assessing
mutagenicity of chemicals, including the methods used for detecting the induced
mutations, bioinformatics tools for analyzing the sequencing data, and chemicals
whose mutagenicity has been evaluated using NGS. Available information suggests
that NGS technology has unparalleled advantages for evaluating mutagenicity of
chemicals can be applied for the next generation of mutagenicity tests.
PMID- 28506111
TI - Re: "Comprehensive Survey Results of Childhood Thyroid Ultrasound Examinations in
Fukushima in the First Four Years After the Fukushima Daiichi Nuclear Power Plant
Accident" by Suzuki et al. (Thyroid 2016;26:843-851).
PMID- 28506112
TI - Resting Bradycardia, Enhanced Postexercise Heart Rate Recovery and
Cardiorespiratory Fitness in Recreational Ballroom Dancers.
AB - PURPOSE: In a cross-sectional study design, we evaluated the resting heart rate
(HRbaseline) and exercise and postexercise stress test-related chronotropic
responses in male practitioners of recreational ballroom dancing (BD; n = 25,
Mage = 26.6 +/- 6.1 years) compared to a control group of insufficiently active
nondancers (CG; n = 25, Mage = 25.9 +/- 4.5 years). METHOD: All participants
underwent a submaximal exercise test. At 85% of the maximal predicted HR, the
recovery protocol was started, and heart rate recovery (HRR) was recorded during
1-min intervals for 5 min. RESULTS: Compared with CG, BD showed lower HRbaseline
(70 beats per minute [bpm] vs. 62 bpm, respectively, U = 143, p < .05, ES = .46),
lower preexercise HR (94 bpm vs. 86 bpm, U = 157, p < .05, ES = .42), longer
exercise test duration (346 s vs. 420 s, U = 95.5, p < .05, ES = .59), and higher
HRR for 5 min postexercise (U = 1.29-1.89, p < .05, ES = .33-.50) as follows: 1st
min (32 bpm vs. 40 bpm), 2nd min (45 bpm vs. 53 bpm), 3rd min (51 bpm vs. 58
bpm), 4th min (55 bpm vs. 59 bpm), and 5th min (59 bpm vs. 63 bpm). The
coefficient of HRR from the 1st min to the 5th min postexercise was similar in
both groups (U = 229-311, p > .05, ES = < .10-.22). CONCLUSION: Heightened
cardiovascular functional status characterized by favorable enhanced chronotropic
dynamics appears to occur in practitioners of recreational ballroom dancing,
which suggests that this modality of exercise may result in health benefits.
PMID- 28506113
TI - The occurrence of ryegrass staggers and heat stress in sheep grazing ryegrass
endophyte associations with diverse alkaloid profiles.
AB - AIMS: To compare ryegrass pastures infected with endophytes producing diverse
alkaloids for their ability to cause ryegrass staggers in grazing lambs; to
compare respiration rates and rectal temperatures of these lambs after exposure
to heat stress, and to compare liveweight gains during the study period. METHODS:
Ryegrass pastures of cultivar Trojan infected with NEA endophytes, branded NEA2
(T-NEA2), endophyte-free Trojan (T-NIL), Samson infected with standard endophyte
(S-STD), Samson infected with AR37 endophyte (S-AR37) and endophyte-free Samson
(S-NIL), were grazed by lambs (n=30 per cultivar) for up to 48 days in February
and March of 2012 and 2013. Pasture samples were analysed for alkaloid
concentrations and lambs were scored for ryegrass staggers at intervals during
the study period. Liveweight was recorded at the start (Day 0) and end of the
study, and rectal temperatures and respiratory rates were measured in lambs
exposed to heat stress on Days 23 and 26, in 2012 and 2013, respectively.
RESULTS: Concentrations of alkaloids were lower in 2012 than 2013, associated
with warmer and drier conditions in 2013, and the prevalence of ryegrass staggers
was low in 2012. In 2013, concentrations of ergovaline were similar in T-NEA2 and
S-STD, but concentrations of lolitrem B were lower in T-NEA2 than S-STD. S-AR37
produced epoxy-janthitrems but no lolitrem B or ergovaline. In 2013, by Day 20,
9/30 (30%) sheep grazing S-STD had severe staggers (score >=4), and by Day 47 all
sheep had been removed from this cultivar due to severe staggers. By Day 47,
18/30 (60%), 4/30 (13%) and 0/30 (0%) sheep grazing S-AR37, T-NEA2 and T-NIL
pastures, respectively, had severe staggers. There were no differences in mean
daily weight gain of lambs between cultivars in either year. In both years, mean
rectal temperature and respiration rate following exposure to heat stress were
highest in sheep grazing S-STD and T-NEA2, and lowest in sheep grazing T-NIL.
CONCLUSIONS: In lambs grazing different ryegrass pastures infected with
endophytes, ryegrass staggers was most severe on S-STD, less severe on S-AR37 and
least on T-NEA2. When under heat stress, lambs grazing ergovaline-producing S-STD
and T-NEA2 pastures had increased respiration rates and rectal temperatures
compared with lambs grazing T-NIL. CLINICAL RELEVANCE: If ambient temperatures
are suitable, NEA2-branded endophytes have the potential to express
concentrations of ergovaline sufficient to induce heat stress in grazing sheep.
PMID- 28506114
TI - The Fatty Liver Index (FLI) Relates to Diabetes-Specific Parameters and an
Adverse Lipid Profile in a Cohort of Nondiabetic, Dyslipidemic Patients.
AB - BACKGROUND: Patients with hyperlipidemia are at high risk for developing a fatty
liver. The fatty liver index (FLI) is a noninvasive and well-established method
for the estimation of a fatty liver. However, little is known about the metabolic
characterization of nondiabetic treated patients with hyperlipidemia who have
different risk levels for a fatty liver. METHODS: In this study, 74 nondiabetic
patients with hyperlipidemia were divided into 3 groups according to their fatty
liver index. A comparison of metabolic characteristics was done. These
characteristics included intima media thickness (IMT) and nutritional habits,
which were further divided into FLI subgroups with low, intermediate, and high
risk for a fatty liver. RESULTS: Patients with hyperlipidemia, with a high risk
for a fatty liver (FLI >= 60), had subclinical elevations in parameters of
carbohydrate metabolism (insulin, fasting plasma glucose, C-peptide) including a
higher insulin resistance (quantitative insulin sensitivity check index, QUICKI)
compared to lower FLI groups. These patients also presented a higher risk for a
metabolic syndrome (p = 0.018), as well as an adverse lipid profile (e.g., high
density lipoprotein [HDL] cholesterol, triglycerides [TG]-HDL ratio). FLI group 3
was characterized by significantly lower levels of omega-3 fatty acids (p =
0.048). CONCLUSION: The fatty liver index relates to diabetes-specific parameters
and an adverse lipid profile and is an appropriate index for risk evaluation of
metabolic syndrome.
PMID- 28506116
TI - Intelligent Adaptive Systems: an interaction-centred design perspective.
PMID- 28506115
TI - Predictors of work participation for Maori 3 months after injury.
AB - An important rehabilitation outcome for injured Maori is a timely sustainable
return to work. This article identifies the factors influencing working after
injury in an attempt to reduce the individual, social, and economic costs. Maori
participants in the Prospective Outcomes of Injury Study were interviewed about
preinjury and injury-related factors. Among Maori participants, 521 were working
for pay prior to injury; 64% were working 3 months postinjury. Factors
identified, using modified Poisson regression, that predicted working include
financial security (aRR = 1.34, 95% CI [1.12, 1.61]), an injury of low (aRR =
1.76, 95% CI [1.26, 2.44]) or moderate severity (aRR = 1.86, 95% CI [1.34,
2.59]), professional occupations (aRR = 1.22, 95% CI [1.03, 1.44]), and jobs with
less repetitive hand movement (aRR = 1.17, 95% CI [1.01, 1.34]). These factors
identified warrant attention when planning interventions to enable rehabilitation
back to the workplace.
PMID- 28506117
TI - Efficiency of a locally designed pilot-scale trickling biofilter (TBF) system in
natural environment for the treatment of domestic wastewater.
AB - In the present study, a cost-effective and simple stone media pilot-scale
trickling biofilter (TBF) was designed, constructed and operated in a continuous
recirculation mode for wastewater treatment with a hydraulic flow rate of 1.2
L/min (Q = 0.072 m3/h) and hydraulic loading (Q/A) of 0.147 m3/day for 15 weeks
at a temperature range of 14.5-36 degrees C. A substantial reduction in the
average concentration of different pollution indicators, such as chemical oxygen
demand (COD) (85.6%), biochemical oxygen demand (BOD5) (85.6%), total dissolved
solid (TDS) (62.8%), total suspended solid (TSS) (99.9%), electrical conductivity
(EC) (15.1%), phosphates (63.22%), sulfates (28.5%) and total nitrogen (TN)
(34.4%), was observed during 15 weeks of operational period. Whereas a
considerable average increase in the levels of dissolved oxygen (DO) (63.2%) was
found after treatment of wastewater by the TBF system. No significant reduction
in most probable number (MPN) index of fecal coliforms was observed in the
effluent in first 9 weeks of operation. However, a significant reduction in the
MPN of fecal coliforms was observed, i.e. 80-90% in the last few weeks of
treatment. Thus, overall results suggest that pilot-scale TBF has a great
potential to be transferred to field scale for treating sewage for small
communities in developing countries, in order to produce effluent of good
quality, which can be safely used for irrigation as well as ornamental purposes.
PMID- 28506118
TI - Effect of a Diet Enriched with Fresh Coconut Saturated Fats on Plasma Lipids and
Erythrocyte Fatty Acid Composition in Normal Adults.
AB - OBJECTIVE: The objective of this study was to compare the effects of increased
saturated fatty acid (SFA) (provided by fresh coconut) versus monounsaturated
fatty acid (MUFA) intake (provided by a combination of groundnuts and groundnut
oil) on plasma lipids and erythrocyte fatty acid (EFA) composition in healthy
adults. MATERIAL AND METHODS: Fifty-eight healthy volunteers, randomized into 2
groups, were provided standardized diet along with 100 g fresh coconut or
groundnuts and groundnut oil combination for 90 days in a Yoga University.
Fasting blood samples were collected before and after the intervention period for
the measurement of plasma lipids and EFA profile. RESULTS: Coconut diet increased
low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels
significantly. In contrast, the groundnut diet decreased total cholesterol (TC),
mainly due to a decrease in HDL levels. There were no differences in the major
SFA of erythrocytes in either group. However, coconut consumption resulted in an
increase in C14:0 and C24:0 along with a decrease in levels of C18:1 n9 (oleic
acid). There was a significant increase in levels of C20:3 n6 (dihomo-gamma
linolenic acid, DGLA). CONCLUSIONS: Consumption of SFA-rich coconut for 3 months
had no significant deleterious effect on erythrocytes or lipid-related factors
compared to groundnut consumption. On the contrary, there was an increase in the
anti-atherogenic HDL levels and anti-inflammatory precursor DGLA in erythrocyte
lipids. This suggests that coconut consumption may not have any deleterious
effects on cardiovascular risk in normal subjects.
PMID- 28506120
TI - Indigenous Peoples of Northern Russia: Anthropology and Health.
PMID- 28506119
TI - Study of the genetic diversity of the aflatoxin biosynthesis cluster in
Aspergillus section Flavi using insertion/deletion markers in peanut seeds from
Georgia, USA.
AB - Aflatoxins are among the most powerful carcinogens in nature. The major aflatoxin
producing fungi are Aspergillus flavus and A. parasiticus. Numerous crops,
including peanut, are susceptible to aflatoxin contamination by these fungi.
There has been an increased use of RNA interference (RNAi) technology to control
phytopathogenic fungi in recent years. In order to develop molecular tools
targeting specific genes of these fungi for the control of aflatoxins, it is
necessary to obtain their genome sequences. Although high-throughput sequencing
is readily available, it is still impractical to sequence the genome of every
isolate. Thus, in this work, the authors proposed a workflow that allowed
prescreening of 238 Aspergillus section Flavi isolates from peanut seeds from
Georgia, USA. The aflatoxin biosynthesis cluster (ABC) of the isolates was
fingerprinted at 25 InDel (insertion/deletion) loci using capillary
electrophoresis. All isolates were tested for aflatoxins using ultra-high
performance liquid chromatography. The neighbor-joining, three-dimension (3D)
principal coordinate, and Structure analyses revealed that the Aspergillus
isolates sampled consisted of three main groups determined by their capability to
produce aflatoxins. Group I comprised 10 non-aflatoxigenic A. flavus; Group II
included A. parasiticus; and Group III included mostly aflatoxigenic A. flavus
and the three non-aflatoxigenic A. caelatus. Whole genomes of 10 representative
isolates from different groups were sequenced. Although InDels in Aspergillus
have been used by other research groups, this is the first time that the cluster
analysis resulting from fingerprinting was followed by whole-genome sequencing of
representative isolates. In our study, cluster analysis of ABC sequences
validated the results obtained with fingerprinting. This shows that InDels used
here can predict similarities at the genome level. Our results also revealed a
relationship between groups and their capability to produce aflatoxins. The
database generated of Aspergillus spp. can be used to select target genes and
assess the effectiveness of RNAi technology to reduce aflatoxin contamination in
peanut.
PMID- 28506122
TI - Examining transitions from youth to adult services for young persons with autism.
AB - Autism Spectrum Disorder (ASD) presents pervasive challenges for individuals
throughout their lifetime. Although some financial, community, and individual
supports are available for children, there are fewer resources available for
adults with ASD, their families, and/or caregivers. It is important to understand
the multidimensional shifts associated with the transition from adolescence to
adulthood for individuals with ASD. To better understand the transitional
process, a qualitative study comprised 11 semi-structured interviews with
individuals with ASD and their families. Interviews elicited the experiences of
individuals and families impacted by ASD as they transition to adulthood and
adult systems of care. This study found that individuals with ASD and their
family are exposed to a "lifetime of difficult transitions" due to a limited
number of service providers and resources including stringent and restrictive
program and funding criteria. As a result, individuals with ASD and their
families were concerned about the ability of some individuals with ASD to
establish meaningful lives in adulthood. These findings challenge existing
barriers and broader societal values and stigma that impede emerging adults with
developmental disabilities.
PMID- 28506123
TI - Jack'd, a Mobile Social Networking Application: A Site of Exclusion Within a Site
of Inclusion.
AB - User-generated smartphone applications have created a new level of virtual
connectivity for gay males, one in which users can create profiles and meet other
users as nearby or as far away as possible. For those within close proximity, the
other users can be considered their "virtual neighbors." Although the
applications are theoretically designed to be places of inclusion and not
exclusion, where any gay male with economic means can download an application,
many profiles have been created that exclude other users. Through an examination
of profiles on one such application, Jack'd, exclusion is found in the way users
celebrate and reinforce ideas of traditional masculinity and denigrate and
reinforce stereotypic ideas of femininity embodied by some gay men. Jack'd, and
other user-generated smartphone applications, can be read as virtual
neighborhoods where one is excluded based on their gender performance.
PMID- 28506121
TI - Mammalian Circadian Period, But Not Phase and Amplitude, Is Robust Against Redox
and Metabolic Perturbations.
AB - AIMS: Circadian rhythms permeate all levels of biology to temporally regulate
cell and whole-body physiology, although the cell-autonomous mechanism that
confers ~24-h periodicity is incompletely understood. Reports describing
circadian oscillations of over-oxidized peroxiredoxin abundance have suggested
that redox signaling plays an important role in the timekeeping mechanism. Here,
we tested the functional contribution that redox state and primary metabolism
make to mammalian cellular timekeeping. RESULTS: We found a circadian rhythm in
flux through primary glucose metabolic pathways, indicating rhythmic NAD(P)H
production. Using pharmacological and genetic perturbations, however, we found
that timekeeping was insensitive to changes in glycolytic flux, whereas oxidative
pentose phosphate pathway (PPP) inhibition and other chronic redox stressors
primarily affected circadian gene expression amplitude, not periodicity. Finally,
acute changes in redox state decreased PER2 protein stability, phase dependently,
to alter the subsequent phase of oscillation. INNOVATION: Circadian rhythms in
primary cellular metabolism and redox state have been proposed to play a role in
the cellular timekeeping mechanism. We present experimental data testing that
hypothesis. CONCLUSION: Circadian flux through primary metabolism is cell
autonomous, driving rhythmic NAD(P)+ redox cofactor turnover and maintaining a
redox balance that is permissive for circadian gene expression cycles. Redox
homeostasis and PPP flux, but not glycolysis, are necessary to maintain clock
amplitude, but neither redox nor glucose metabolism determines circadian period.
Furthermore, cellular rhythms are sensitive to acute changes in redox balance, at
least partly through regulation of PER protein. Redox and metabolic state are,
thus, both inputs and outputs, but not state variables, of cellular circadian
timekeeping. Antioxid. Redox Signal. 28, 507-520.
PMID- 28506124
TI - Fluid intelligence: A brief history.
AB - The concept of fluid and crystallized intelligence was introduced to the
psychological community approximately 75 years ago by Raymond B. Cattell, and it
continues to be an area of active research and controversy. The purpose of this
paper is to provide a brief overview of the origin of the concept, early efforts
to define intelligence and uses of intelligence tests to address pressing social
issues, and the ongoing controversies associated with fluid intelligence and the
structure of intelligence. The putative neuropsychological underpinnings and
neurological substrates of fluid intelligence are discussed.
PMID- 28506125
TI - Hemoglobin A1c as a Predictor of Postoperative Infection Following Elective
Forefoot Surgery.
AB - BACKGROUND: There remains little evidence to support a perioperative hemoglobin
A1c (HbA1c) level that could serve as a threshold for a significantly increased
risk of postoperative surgical site infection (SSI) following forefoot surgery.
METHODS: A national database was queried for patients who underwent elective
forefoot surgery with diabetes. Patients with a perioperative HbA1c level within
3 months of surgery were identified and stratified based on HbA1c level in 0.5
mg/dL increments. The incidence of SSI was determined by either a diagnosis or
procedure for SSI within 1 year and a receiver operating characteristic (ROC)
curve and area under the curve (AUC) analysis was performed to determine an
optimal threshold value of HbA1c. RESULTS: A total of 4630 patients who underwent
forefoot surgery with diabetes with a perioperative HbA1c were included. The rate
of SSI ranged from 2.3% to 11.8%. The inflection point of the ROC curve
corresponded to an HbA1c level above 7.5 mg/dL ( P < .0001; 95% confidence
interval [CI] = 0.58-0.67; AUC = 0.631; specificity = 75%; sensitivity = 46%).
After multivariate analysis, patients with an HbA1c level of 7.5 mg/dL or greater
had a significantly higher risk for postoperative wound infection compared to
patients below this threshold (OR = 1.92; 95% CI = 1.5-2.4; P < .0001).
CONCLUSIONS: The risk of postoperative SSI following forefoot surgery increased
as the perioperative HbA1c increased. ROC analysis determined that a
perioperative HbA1c above 7.5 mg/dL could serve as a threshold for a
significantly increased risk of postoperative SSI following forefoot surgery.
LEVEL OF EVIDENCE: Level III, comparative series.
PMID- 28506126
TI - Intergenerational Programs May Be Especially Engaging for Aged Care Residents
With Cognitive Impairment: Findings From the Avondale Intergenerational Design
Challenge.
AB - Intergenerational programs are an authentic way to engage elders in meaningful
activity and report benefits to both elders and youth. The Avondale
Intergenerational Design Challenge (AVID) randomly assigned small teams of
technology students aged 13 to 15 years (total N = 59) to 1 of 24 aged care
residents with a range of cognitive impairment. Students met with the resident 4
times over 15 weeks and ultimately crafted a personalized item for them. Students
showed no change in self-reported attitudes to elders, empathy, or self-esteem
post-AVID or at 3-month follow-up, compared to a 3-month within-subject control
period pre-AVID. Compared to usual lifestyle activities, residents showed
significant improvements in self-reported positive affect and negative affect
after student visits and were observed to be significantly more engaged during
visits, especially residents with greater cognitive impairment. The personal and
guided nature of intergenerational programs may be especially effective in
engaging elders with cognitive impairment in meaningful activity.
PMID- 28506127
TI - Living into death: a case for an iterative, fortified and cross-sector approach
to advance care planning.
AB - Advance care planning (ACP) has been framed as best practice for quality
palliative care, yet a growing body of literature affirms the need for an early
iterative ACP process to begin when people are young and healthy. A significant
gap appears to exist in the literature regarding the utility of death
conversations outside the end-of-life context. Could 'death conversations' early
in life be an effective tool by which doctor and patient can co-construct a more
healthful way of life, and realistic relationship with death? And what variables
must be taken into account for these conversations to proceed successfully? This
paper provides a narrative exploration of the value of death conversations in the
clinical context in New Zealand. Five exemplars are discussed, drawn from a
sample of 21 semi-structured interviews with young older adults (54-65 years old)
not receiving palliative care or diagnosed with a terminal illness. Together,
these narratives indicate that further community consultation is required to
determine culturally appropriate ways to initiate productive conversations around
aging, death and dying and how to build patient/practitioner/family relationships
which allow these conversations to happen safely. There is a need to acknowledge
the important factor of culture related to age, generation, sex, faith and
ethnicity when engaging in conversations about aging, death and dying. By doing
so, health professionals will be best equipped to assist their patients to live
well into death.
PMID- 28506128
TI - A review of curcumin as a biological stain and as a self-visualizing
pharmaceutical agent.
AB - Curcumin has been widely used to color textiles but, unlike other natural dyes
such as hematoxylin or saffron, it rarely has been discussed as a biological
stain. Aspects of the physicochemistry of curcumin relevant to biological
staining and self-visualization, i.e., its acidic properties, lipophilicity,
metal and pseudometal complexes, and optical properties, are summarized briefly
here. Reports of staining of non-living biological specimens in sections and
smears, both fixed and unfixed, including specimens embedded in resin, are
summarized here. Staining of amyloid, boron and chromatin are outlined and
possible reaction mechanisms discussed. Use of curcumin as a vital stain also is
described, both in cultured monolayers and in whole organisms. Staining
mechanisms are considered especially for the selective uptake of curcumin into
cancer cells. Staining with curcumin labeled nanoparticles is discussed. Toxicity
and safety issues associated with the dye also are presented.
PMID- 28506129
TI - Kidney injury in infants and children with iron-deficiency anemia before and
after iron treatment.
AB - BACKGROUND: Our study aimed to investigate the effects of iron-deficiency anemia
(IDA) on renal tubular functions before and after iron treatment for infants and
children with IDA. We measured urinary levels of two kidney injury markers:
neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid
binding protein (L-FABP). MATERIAL AND METHODS: Thirty-six infants and children
with IDA and 20 matched healthy controls were included. We assessed different
laboratory parameters, estimated glomerular filtration rate, urinary levels of
NGAL, and L-FABP. Urinary kidney injury markers were measured in IDA patients
before and after 3 months of oral iron therapy. RESULTS: IDA patients had
significantly higher urinary NGAL and L-FABP levels compared to their healthy
controls. After 3 months of oral iron treatment, there was a significant
improvement (decrease) in urinary NGAL and L-FABP in infants and children with
IDA. Urinary markers returned to normal levels (healthy control levels) in
children with IDA, but not for infants with IDA compared to their healthy
controls. CONCLUSION: Subclinical kidney injury was found in infants and children
with IDA. This injury was completely reversible in older children with IDA and
partially reversible in infants with IDA after iron therapy. Higher urinary
levels of kidney injury molecules in IDA infants after iron treatment are
suggestive of more sensitivity of these infants to oxidative stress caused by
iron therapy or may be due to the immaturity of the kidney and more damage caused
by IDA which may require more time to recover.
PMID- 28506130
TI - Fullerenol nanoparticles decrease ischaemia-induced brain injury and oedema
through inhibition of oxidative damage and aquaporin-1 expression in ischaemic
stroke.
AB - BACKGROUND: We examined the possible protective effects of fullerenol
nanoparticles on brain injuries and oedema in experimental model of ischaemic
stroke through inhibition of oxidative damage and aquaporin-1 (AQP-1) expression.
METHODS: Experiment was done in three groups of rats (N = 66): sham, control
ischaemia and ischaemic treatment. Ischaemia was induced by 90-minutes middle
cerebral artery occlusion (MCAO) followed by 24 hours of reperfusion. Rats
received a dose of 10 mg/kg of fullerenol 30 minutes before MCAO. Infarction,
brain oedema, malondialdehyde (MDA) and nitrate contents as well as mRNA level of
AQP-1 were determined 24 hours after termination of MCAO. RESULTS: Administration
of fullerenol before MCAO significantly reduced the infarction of cortex and
striatum by 72 and 77%, respectively. MCAO induced brain oedema in control
ischaemic rats (3.83 +/- 0.53%), whereas, fullerenol significantly reduced it
(0.91 +/- 0.55%). The contents of MDA and nitrate increased in ischaemic
hemispheres by 86 and 41%, respectively. Fullerenol considerably reduced the MDA
and nitrate contents by 83 and 48%, respectively. Moreover, MCAO noticeably
increased the mRNA level of AQP-1 in ischaemic hemispheres by 22%, whereas
fullerenol significantly decreased it by 29%. DISCUSSION: Fullerenol is able to
reduce ischaemia-induced brain injuries and oedema possibly through inhibition of
oxidative damage and AQP-1 expression in ischaemic stroke.
PMID- 28506131
TI - New drugs and allogeneic hematopoietic stem cell transplantation for
hematological malignancies: do they have a role in bridging, consolidating or
conditioning transplantation treatment?
AB - INTRODUCTION: Novel targeted therapies and monoclonal antibodies can be combined
with allogeneic stem cell transplantation (allo-SCT) at different time-points: 1)
before the transplant to reduce tumour burden, 2) as part of the conditioning in
place of or in addition to conventional agents 3) after the transplant to allow
long-term disease control. Areas covered: This review focuses on the current
integration of new drugs with allo-SCT for the treatment of major hematological
malignancies for which allo-SCT has been a widely-adopted therapy. Expert
opinion: After having been used as single agent salvage treatments in relapsed
patients after allo-SCT or in combination with donor lymphocyte infusions, many
new drugs have also been safely employed before allo-SCT as a bridge to
transplantation or after it as planned consolidation/maintenance. This era of new
drugs has opened new important opportunities to 'smartly' combine 'targeted drugs
and cell therapies' in new treatment paradigms that may lead to higher cure rates
or longer disease control in patients with hematological malignancies.
PMID- 28506132
TI - Lanreotide in the management of small bowel angioectasias: seven-year data from a
tertiary centre.
AB - BACKGROUND AND AIMS: Haemorrhage from small bowel angioectasias (SBAs) can be
debilitating to patients who are very often elderly and have multiple
comorbidities. Our aim was to assess the use of lanreotide in addition to
endotherapy in patients with SBAs. METHOD: Patients with SBAs on capsule
endoscopy (CE) who received lanreotide injections from January 2010 to till the
present day at the Royal Hallamshire Hospital in Sheffield were included.
Baseline demographics were recorded. Efficacy was evaluated in terms of
improvement in mean haemoglobin, transfusion requirements and bleeding episodes.
RESULTS: Twelve patients (67% males, mean age 74 SD +/- 15.5 years) were
included. All patients had multiple comorbidities. Lanreotide was given at a
dosage of 60 mg (42%), 90 mg (33%) or 120 mg (25%). It was given at a four-week
interval in 75% of patients and at a six-week interval in 17% of patients. One
patient (8%) received a single dose. The mean duration of treatment was 19 months
SD +/- 14.5. Only 17% of patients had their lanreotide stopped due to
cholelithiasis. There was a significant improvement in mean haemoglobin: 86.8
versus 98.0 (131-166 g/L, p = .012). The mean number of bleeding episodes (4.18
versus 1.09, p = .010) and packed red cells (323 versus 152, p = .006) received
improved. Patients required less DBEs +/- APCs after starting lanreotide (19
versus 11 p = .048). CONCLUSION: Lanreotide is a useful adjuvant treatment to
therapeutic enteroscopy in patients with refractory obscure gastrointestinal
bleeding due to SBAs. It improves haemoglobin levels, reduces transfusion
requirements, bleeding episodes and number of DBEs. Overall, it has a good safety
profile.
PMID- 28506133
TI - Clinical outcomes following surgically repaired bucket-handle meniscus tears.
AB - OBJECTIVES: Meniscus tears are one of the most common knee injuries. Our goal is
to investigate the failure rate for surgically repaired bucket-handle meniscus
tears and compare clinical outcomes of repairs that failed versus those that did
not, at a minimum 2-year follow-up interval. METHODS: 51 patients were identified
in this retrospective cohort study who experienced bucket-handle meniscus tears
that were isolated or with concomitant ACL injury. Inclusion criteria included
age range from 13-55 years, confirmed bucket-handle meniscus tear by MRI and
intraoperatively, and at least two-years of post-operative follow-up following
index repair. Demographic data and outcome surveys were collected at a minimum of
two-years follow-up after repair. RESULTS: Of the 51 patients that had a bucket
handle meniscal repair, 12 (23.5%) were defined as failures (return of symptoms
alongside re-tear in the same zone of the repaired meniscus within two years of
surgery). No demographic variables (age, sex, and BMI smoking status, location of
tear, or concomitant ACL tear) significantly correlated with failure. The mean of
the Sports and Recreation KOOS was significantly lower between the non-failure
(87 +/- 14.4) and failure (70 +/- 17.2) cohorts (p = 0.0072). The Quality of Life
subscale was significantly lower between the non-failure (76 +/- 15.8) and
failure (57 +/- 18.2) groups (p = 0.0058). There was a significant difference in
the post-operative Lysholm scores (p = 0.0039) with a mean of 90 +/- 9.1 for the
entire cohort and means of 92 +/- 8.4 and 83 +/- 8.6, for non-failure and failure
groups, respectively. CONCLUSIONS: We found a higher failure rate (23.5%) for
bucket-handle meniscus repairs at two-year follow up than has been cited in the
literature, which is typically less than 20%, with significantly lower KOOS
Quality of Life and Sports and Recreation subscales and Lysholm scores for the
failure cohort. This is the first study to report these outcome scores solely for
bucket-handle meniscus repairs, shedding light on the post-operative quality of
life of patients with repair success or failure.
PMID- 28506134
TI - Efficacy and safety of etanercept in psoriasis and psoriatic arthritis in the
PRESTA study: analysis in patients from Central and Eastern Europe.
AB - BACKGROUND: Data are limited on the effectiveness of anti-TNF and other biologics
on psoriatric arthritis (PsA) in Central and Eastern Europe (CEE). The objective
of this analysis was to evaluate the efficacy of etanercept (ETN) in PsA patients
from CEE. METHODS: In PRESTA, patients were randomized to receive ETN 50 mg BIW
or 50 mg QW for 12 weeks (double-blind phase) and ETN 50 mg QW for 12 additional
weeks (open label). In this analysis, only patients from Czech Republic, Hungary,
Poland and Serbia were included. The primary efficacy variable was the proportion
of subjects achieving a physician global assessment (PGA) of psoriasis status:
"clear" or "almost clear" at week 12. RESULTS: In the 307 patients, 54% BIW/QW
compared with 40% (QW/QW) (p = .02), achieved "clear"/"almost clear" for PGA of
psoriasis at week 12 increasing, to 68% and 60%, respectively (p = .134) by week
24. Mean improvement from baseline in PASI were 59% versus 49% (p = .005) at week
6 and 87% versus 81% (p < .05) at week 24, for the BIW/QW and QW/QW groups,
respectively. ETN was well tolerated in both groups over 24 weeks. CONCLUSIONS:
Both dose regimens of ETN provided significant improvements in efficacy in PsA
treatment and were well tolerated.
PMID- 28506135
TI - Emerging cell cycle inhibitors for acute myeloid leukemia.
AB - INTRODUCTION: AML therapy remains very challenging despite our increased
understanding of its molecular heterogeneity. Outcomes with chemotherapy and
targeted therapy remain poor. Targeting cell cycle regulators might complement
chemotherapy and targeted therapy and help in improving outcomes. Areas covered:
Here we cover the pre-clinical and clinical data for both for cyclin dependent
kinase (CDK) and cell-cycle checkpoint inhibitors. While CDK inhibition can
inhibit proliferation, checkpoint inhibitors can facilitate cell cycle
progression in presence of DNA damage and can induce mitotic catastrophe. Expert
opinion: Though the preclinical data for cell cycle inhibitors in AML is
compelling, the clinical translation so far has proven to be challenging. This is
a reflection of the complexity of both, AML and cell cycle regulators. However,
early introduction of cell-cycle active agents in combination with chemotherapy
or targeted agents, identifying right sequence of use and identifying right
biomarkers might pave the way into successful clinical translation.
PMID- 28506136
TI - Predictors to Intravenous Fluid Responsiveness.
AB - Management with intravenous fluids can improve cardiac output in some surgical
patients. Management with static preload indicators, such as central venous
pressure and pulmonary artery occlusion pressure, has not demonstrated a suitable
relationship with changes in the cardiac output induced by intravenous fluid
therapy. Dynamic indicators, such as the variability of arterial pulse pressure
or stroke volume variation, have demonstrated a suitable relationship. Since
improvement in cardiac output does not guarantee an adequate perfusion pressure,
in patients with hypotension, it is also necessary to know whether arterial
pressure will also increase with intravenous fluid therapy. In this regard, the
functional assessment of arterial load by dynamic arterial elastance could help
to determine which patients will improve not only their cardiac output but also
their mean arterial pressure.
PMID- 28506137
TI - Elevation of Serum PARK7 and IL-8 Levels Is Associated With Acute Lung Injury in
Patients With Severe Sepsis/Septic Shock.
AB - OBJECTIVE: Methods containing only clinical information fail to meet the needs of
prediction of acute lung injury (ALI) because of the relatively low positive
predictive value. This study aimed to investigate the feasibility of using
biomarkers as predictors of ALI in populations with severe sepsis/septic shock
and to explore difference among biomarkers after adjustment for potential
confounders. METHODS: Serum specimens were collected from patients with severe
sepsis/septic shock (n = 172) presented to the emergency department. Patients
should be ruled out from the study if they were already suffering from ALI or if
they deteriorated into ALI within 6 hours after specimen collection. The
development of ALI of the remaining patients was tracked. RESULTS: Of all
patients with severe sepsis/septic shock who encountered ALI more than 6 hours
succeeding to specimen collection, 19 deteriorated into ALI. Elevation in serum
interleukin 8 (IL-8) and Parkinson disease 7 (PARK7) levels had significant
connection with higher risk of developing ALI ( P = .006; P = .0001). Sepsis
treatment and vasopressor application led to a robust connection between PARK7
and succeeding ALI development. Patients who deteriorated into ALI were
distinguished accurately from patients who avoided ALI using PARK7 or Lung Injury
Prediction Score (LIPS; area under the receiver operating characteristic curve
[AUROC], 0.73 and 0.72 for each). Combination of PARK7 and LIPS ameliorated AUROC
to 0.86 (vs 0.73, P = .05). On the contrary, serum soluble receptor for advanced
glycation end products and von Willebrand factor made no contribution to the
prediction of ALI development. CONCLUSIONS: Patients with PARK7 or IL-8 levels
above normal are more vulnerable to ALI. Patients vulnerable to ALI can be
distinguished with the combination of serum biomarkers and clinical prediction
scores. In addition, the early rise in PARK7 emphasizes the importance of
endothelial injury in the early pathogenesis of ALI.
PMID- 28506138
TI - Responses to post-graduation surveys do not accurately reflect the workforce.
PMID- 28506139
TI - Effects of aging and depression on mnemonic discrimination ability.
AB - Aging and depression have been found to be associated with poorer performance in
mnemonic discrimination. In the current study, a two-response format mnemonic
similarity test, Cognitive Drug Research MST, was used to compare these effects.
Seventy-six participants were tested; with 52 participants in the young group,
aged 18-35 years, and 24 participants in the elderly group, aged 55 years or
older. Twenty-two young participants and 10 elderly participants met DSM-IV
criteria for MDD or dysthymia. Age-related deficits were found for lure
identification and speed of response. Differences in speed of responses to lure
images were found for younger depressed participants, and depressive symptom
severity was found to be negatively associated with lure identification accuracy
in the elderly. These findings may be viewed as putative behavioral correlates of
decreased pattern separation ability, which may be indicative of altered
hippocampal neurogenesis in aging and depression.
PMID- 28506140
TI - A Multifaceted Hypnosis Smoking-Cessation Program: Enhancing Motivation and Goal
Attainment.
AB - Smoking cessation remains a major health priority. Despite public campaigns
against smoking and widespread availability of smoking-cessation treatments, many
people continue to smoke. The authors argue that the "problem of motivation,"
that is, suboptimal or fluctuating motivation to resist smoking urges and to
comply with the demands of treatment, commonly undermines treatment seeking and
adherence, appreciably reducing the success rates of smoking-cessation programs.
The authors describe the history of the Winning Edge smoking-cessation program
and discuss ways to enhance motivation before, during, and after formal
treatment. They illustrate how hypnotic suggestions, administered in the context
of their program, can promote cognitive, behavioral, and emotional commitment to
treatment and enhance motivation to live a smoke-free life.
PMID- 28506141
TI - A Pragmatic Guide to the Setting up of Integrated Hypnotherapy Services in
Primary Care and Clinical Settings.
AB - Despite the continued debate and lack of a clear consensus about the true nature
of the hypnotic phenomenon, hypnosis is increasingly being utilized successfully
in many medical, health, and psychological spheres as a research method,
motivational tool, and therapeutic modality. Significantly, however, although
hypnotherapy is widely advertised, advocated, and employed in the private medical
arena for the management and treatment of many physical and emotional disorders,
too little appears to be being done to integrate hypnosis into primary care and
national health medical services. This article discusses some of the reasons for
the apparent reluctance of medical and scientific health professionals to
consider incorporating hypnosis into their medical practice, including the
practical problems inherent in using hypnosis in a medical context and some
possible solutions.
PMID- 28506142
TI - The Frustrated and Helpless Healer: Pathways Approaches to Posttraumatic Stress
Disorders.
AB - Posttraumatic stress disorder is a psychophysiological disorder, characterized by
the following: chronic sympathetic nervous activation; persisting
perceptual/sensory vigilance for threats; recurrent distressing memories of the
event, including intrusive memories, flashbacks lived as if in the present
moment, and nightmares; and a persisting negative emotional state including fear
and shame. The psychophysiological basis for this disorder calls for
psychophysiologically based interventions. This article presents the case
narrative of a 29-year-old national guardsman, exposed to combat trauma and later
to civilian trauma in public safety work. His treatment followed the Pathways
model, comprised of multimodal interventions, beginning with self-directed
behavioral changes, then the acquisition of skills (including self-hypnosis), and
finally professional treatment including clinical hypnosis and EMDR.
PMID- 28506143
TI - Future-Focused Therapeutic Strategies for Integrative Health.
AB - For many years, the therapy field was dominated by a focus on the past. In this
context, many clinicians were trained to use hypnosis as a tool to explore the
past, and there is a rich literature documenting the use of hypnosis as a tool to
induce age regression and the uncovering of traumatic memories. This article
presents a therapeutic paradigm that focuses on the future. Hypnosis is used to
induce creativity, flexibility, and openness to the future. In the context of
health care, hypnosis is used to explore the best possible treatment outcome,
which may be pharmacological, surgical, or a combination of both as well as other
nonsurgical interventions. This article elaborates on the effective use of a
therapeutic hypnosis strategy and technique focused on the future.
PMID- 28506145
TI - Areas of Control Desired by Patients and Families Referred to Hospice Care:
Perspectives of Hospice Admissions Staff.
AB - Sense of control in end-of-life (EOL) care plays a critical role in the patient's
well-being. However, little is known about the areas of control essential to
patients and families at a specific time point in the illness trajectory: when
patients stop curative treatments and are referred to hospice. This study
qualitatively explored such areas. Sixteen admissions staff members from four
hospice agencies were interviewed about their perceptions of areas in which
patients and families worried about losing control by accepting hospice. The
thematic analysis revealed four areas of control: changes to medical care, health
care provider changes, use of life-sustaining treatments, and daily life.
Participants of this study put a great emphasis on consistently communicating
their willingness to honor patients' and families' control over their care
decisions and lives. Future research should examine control in EOL care among
diverse populations and effectiveness of hospice staff's strategies to address
desire for control.
PMID- 28506144
TI - Hypnosis for Symptom Control in Cancer Patients at the End-of-Life: A Systematic
Review.
AB - Hypnosis has been shown to alleviate symptoms and side effects of cancer and its
treatment. However, less is known about the use of hypnosis at the end of life in
individuals with cancer. Our goal was to systematically review the literature on
the use of hypnosis to manage the most common symptoms of end-of-life cancer
patients: fatigue, sleep disturbances, pain, appetite loss, and dyspnea. EMBASE,
MEDLINE, COCHRANE, PsychINFO, and SCOPUS databases were searched from inception
through November 7, 2016. No studies met the inclusion criteria. It appears that
hypnosis has never been rigorously tested as a means to ameliorate the most
common symptoms in individuals with cancer at the end of their lives. This
finding is troubling, as it strongly implies that a population most in need has
been largely neglected. However, a clear future research direction is revealed
that may have significant clinical impact.
PMID- 28506146
TI - The Impact of Shoulder Abduction Loading on Volitional Hand Opening and Grasping
in Chronic Hemiparetic Stroke.
AB - BACKGROUND: Up to 60% of individuals with moderate to severe chronic hemiparetic
stroke experience excessive involuntary wrist/finger flexion that constrains
functional hand movements including hand opening. It's not known how stroke
induced brain injury impacts volitional hand opening and grasping forces as a
result of the expression of abnormal coupling between shoulder abduction and
wrist/finger flexion or the flexion synergy. OBJECTIVE: The goal of this study is
to understand how shoulder abduction loading affects volitional hand opening and
grasping forces in individuals with moderate to severe chronic hemiparetic
stroke. METHODS: Thirty-six individuals (stroke, 26; control, 10) were recruited
for this study. Each participant was instructed to perform maximal hand opening
and grasping forces while the arm was either fully supported or lifted with a
weight equal to 25% or 50% of the participant's maximal shoulder abduction
torque. Hand pentagon area, defined as the area formed by the tips of thumb and
fingers, was calculated during hand opening. Forces were recorded during
grasping. RESULTS: In individuals with moderate stroke, increasing shoulder
abduction loading reduced the ability to maximally open the hand. In individuals
with severe stroke, who were not able to open the hand, grasping forces were
generated and increased with shoulder abduction loading. Stroke individuals also
showed a reduced ability to control volitional grasping forces due to the
enhanced expression of flexion synergy. CONCLUSIONS: Shoulder abduction loading
reduced the ability to volitionally open the hand and control grasping forces
after stroke. Neural mechanisms and clinical implications of these findings are
discussed.
PMID- 28506147
TI - Long-term Outcome After Survival of a Cardiac Arrest: A Prospective Longitudinal
Cohort Study.
AB - BACKGROUND: A cardiac arrest can lead to hypoxic brain injury, which can affect
all levels of functioning. OBJECTIVE: To investigate 1-year outcome and the
pattern of recovery after surviving a cardiac arrest. METHODS: This was a
multicenter, prospective longitudinal cohort study with 1 year of follow-up
(measurements 2 weeks, 3 months, 1 year). On function level, physical/cardiac
function (New York Heart Association Classification), cognition (Cognitive Log
[Cog-log], Cognitive Failures Questionnaire), emotional functioning (Hospital
Anxiety and Depression Scale, Impact of Event Scale), and fatigue (Fatigue
Severity Scale) were assessed. In addition, level of activities (Frenchay
Activities Index, FAI), participation (Community Integration Questionnaire [CIQ]
and return to work), and quality of life (EuroQol 5D, EuroQol Visual Analogue
Scale, SF-36, Quality of Life after Brain Injury) were measured. RESULTS: In this
cohort, 141 cardiac arrest survivors were included. At 1 year, 14 (13%) survivors
scored below cutoff on the Cog-log. Both anxiety and depression were present in
16 (15%) survivors, 29 (28%) experienced posttraumatic stress symptoms and 55
(52%), severe fatigue. Scores on the FAI and the CIQ were, on average,
respectively 96% and 92% of the prearrest scores. Of those previously working, 41
(72%) had returned to work. Most recovery of cognitive function and quality of
life occurred within the first 3 months, with further improvement on some domains
of quality of life up to 12 months. CONCLUSIONS: Overall, long-term outcome in
terms of activities, participation, and quality of life after cardiac arrest is
reassuring. Nevertheless, fatigue is common; problems with cognition and emotions
occur; and return to work can be at risk.
PMID- 28506148
TI - Large-Scale Phase Synchrony Reflects Clinical Status After Stroke: An EEG Study.
AB - BACKGROUND AND PURPOSE: Stroke-induced focal brain lesions often exert remote
effects via residual neural network activity. Electroencephalographic (EEG)
techniques can assess neural network modifications after brain damage. Recently,
EEG phase synchrony analyses have shown associations between the level of large
scale phase synchrony of brain activity and clinical symptoms; however, few
reports have assessed such associations in stroke patients. OBJECTIVE: The aim of
this study was to investigate the clinical relevance of hemispheric phase
synchrony in stroke patients by calculating its correlation with clinical status.
METHODS: This cross-sectional study included 19 patients with post-acute ischemic
stroke admitted for inpatient rehabilitation. Interhemispheric phase synchrony
indices (IH-PSIs) were computed in 2 frequency bands (alpha [alpha], and beta
[beta]), and associations between indices and scores of the Functional
Independence Measure (FIM), the National Institutes of Health Stroke Scale
(NIHSS), and the Fugl-Meyer Motor Assessment (FMA) were analyzed. For further
assessments of IH-PSIs, ipsilesional intrahemispheric PSIs (IntraH-PSIs) as well
as IH- and IntraH-phase lag indices (PLIs) were also evaluated. RESULTS: IH-PSIs
correlated significantly with FIM scores and NIHSS scores. In contrast, IH-PSIs
did not correlate with FMA scores. IntraH-PSIs correlate with FIM scores after
removal of the outlier. The results of analysis with PLIs were consistent with IH
PSIs. CONCLUSIONS: The PSIs correlated with performance on the activities of
daily living scale but not with scores on a pure motor impairment scale. These
results suggest that large-scale phase synchrony represented by IH-PSIs provides
a novel surrogate marker for clinical status after stroke.
PMID- 28506150
TI - Chronic Stroke Survivors Improve Reaching Accuracy by Reducing Movement
Variability at the Trained Movement Speed.
AB - BACKGROUND: Recovery from stroke is often said to have "plateaued" after 6 to 12
months. Yet training can still improve performance even in the chronic phase.
Here we investigate the biomechanics of accuracy improvements during a reaching
task and test whether they are affected by the speed at which movements are
practiced. METHOD: We trained 36 chronic stroke survivors (57.5 years, SD +/-
11.5; 10 females) over 4 consecutive days to improve endpoint accuracy in an arm
reaching task (420 repetitions/day). Half of the group trained using fast
movements and the other half slow movements. The trunk was constrained allowing
only shoulder and elbow movement for task performance. RESULTS: Before training,
movements were variable, tended to undershoot the target, and terminated in
contralateral workspace (flexion bias). Both groups improved movement accuracy by
reducing trial-to-trial variability; however, change in endpoint bias (systematic
error) was not significant. Improvements were greatest at the trained movement
speed and generalized to other speeds in the fast training group. Small but
significant improvements were observed in clinical measures in the fast training
group. CONCLUSIONS: The reduction in trial-to-trial variability without an
alteration to endpoint bias suggests that improvements are achieved by better
control over motor commands within the existing repertoire. Thus, 4 days'
training allows stroke survivors to improve movements that they can already make.
Whether new movement patterns can be acquired in the chronic phase will need to
be tested in longer term studies. We recommend that training needs to be
performed at slow and fast movement speeds to enhance generalization.
PMID- 28506149
TI - A Short and Distinct Time Window for Recovery of Arm Motor Control Early After
Stroke Revealed With a Global Measure of Trajectory Kinematics.
AB - BACKGROUND: Studies demonstrate that most arm motor recovery occurs within three
months after stroke, when measured with standard clinical scales. Improvements on
these measures, however, reflect a combination of recovery in motor control,
increases in strength, and acquisition of compensatory strategies. OBJECTIVE: To
isolate and characterize the time course of recovery of arm motor control over
the first year poststroke. METHODS: Longitudinal study of 18 participants with
acute ischemic stroke. Motor control was evaluated using a global kinematic
measure derived from a 2-dimensional reaching task designed to minimize the need
for antigravity strength and prevent compensation. Arm impairment was evaluated
with the Fugl-Meyer Assessment of the upper extremity (FMA-UE), activity
limitation with the Action Research Arm Test (ARAT), and strength with biceps
dynamometry. Assessments were conducted at: 1.5, 5, 14, 27, and 54 weeks
poststroke. RESULTS: Motor control in the paretic arm improved up to week 5, with
no further improvement beyond this time point. In contrast, improvements in the
FMA-UE, ARAT, and biceps dynamometry continued beyond 5 weeks, with a similar
magnitude of improvement between weeks 5 and 54 as the one observed between weeks
1.5 and 5. CONCLUSIONS: Recovery after stroke plateaued much earlier for arm
motor control, isolated with a global kinematic measure, compared to motor
function assessed with clinical scales. This dissociation between the time
courses of kinematic and clinical measures of recovery may be due to the
contribution of strength improvement to the latter. Novel interventions, focused
on the first month poststroke, will be required to exploit the narrower window of
spontaneous recovery for motor control.
PMID- 28506151
TI - A new primary mobility tool for the visually impaired: A white cane-adaptive
mobility device hybrid.
AB - This article describes pilot testing of an adaptive mobility device-hybrid (AMD
H) combining properties of two primary mobility tools for people who are blind:
the long cane and adaptive mobility devices (AMDs). The long cane is the primary
mobility tool used by people who are blind and visually impaired for independent
and safe mobility and AMDs are adaptive devices that are often lightweight frames
approximately body width in lateral dimension that are simply pushed forward to
clear the space in front of a person. The prototype cane built for this study had
a wing apparatus that could be folded around the shaft of a cane but when
unfolded, deployed two wheeled wings 25 cm (9.8 in) to each side of the canetip.
This project explored drop-off and obstacle detection for 6 adults with visual
impairment using the deployed AMD-H and a standard long cane. The AMD-H improved
obstacle detection overall, and was most effective for the smallest obstacles (2
and 6 inch diameter). The AMD-H cut the average drop off threshold from 1.79
inches (4.55 cm) to .96 inches (2.44 cm). All participants showed a decrease in
drop off detection threshold and an increase in detection rate (13.9% overall).
For drop offs of 1 in (2.54 cm) and 3 in (7.62 cm), all participants showed large
improvements with the AMD-H, ranging from 8.4 to 50%. The larger drop offs of 5
in (12.7 cm) and 7 in (17.8 cm) were well detected by both types of canes.
PMID- 28506152
TI - A participatory systems approach to design for safer integrated medicine
management.
AB - It is recognised that whole systems approaches are required in the design and
development of complex health care services. Application of a systems approach
benefits from the involvement of key stakeholders. However, participation in the
context of community based health care is particularly challenging due to busy
and geographically distributed stakeholders. This study used action research to
investigate what processes and methods were needed to successfully employ a
participatory systems approach. Three participatory workshops planned and
facilitated by method experts were held with 30 representative stakeholders.
Various methods were used with them and evaluated through an audit of workshop
outputs and a qualitative questionnaire. Findings on the method application and
participation are presented and methodological challenges are discussed with
reference to further research. Practitioner Summary: This study provides
practical insights on how to apply a participatory systems approach to complex
health care service design. Various template-based methods for systems thinking
and risk-based thinking were efficiently and effectively applied with
stakeholders.
PMID- 28506153
TI - Design and experimental evaluation of yoked hand-clutching for a lever drive
chair.
AB - Lever-drive wheelchairs lower physical strain but are less maneuverable than push
rim wheelchairs. Here, we study a possible solution in which the user
simultaneously actuates clutches mounted between the levers and wheels each
stroke via a clutch handle attached to one lever; this solution is of particular
interest for user groups with only one functional hand. First, to demonstrate
maneuverability, we show how this "yoked clutch" allows an experienced user to
maneuver a constrained space. Then, we compared the difficulty of learning a
yoked clutch chair to a conventional lever-drive transmission (i.e. a one-way
bearing). Twenty-two unimpaired novice adults navigated a figure-eight track
during six training sessions over two weeks. Participant mean speed improved
roughly 60% for both chairs, with similar exponential improvement time constants
(3 days) and final speeds. However, speed improvement mostly took place overnight
rather than within the session for hand-clutching, and the physiological cost
index was also about 40% higher. These results indicate that while hand-clutching
is no more difficult to learn than a lever-drive, it is reliant on overnight
improvement. Also, its increased maneuverability comes with decreased efficiency.
We discuss how the yoked clutch may be particularly well suited for individuals
with stroke during inpatient rehabilitation.
PMID- 28506155
TI - Confounding by Symptomatic Mefloquine Exposure in Military Studies of Post
Traumatic Stress Disorder.
PMID- 28506156
TI - Flexor Digitorum Superficialis Tendon Sling Volar Plate Reconstruction for Swan
Neck Deformity in the Spastic Finger.
AB - The condition of proximal interphalangeal joint (PIPJ) locking in hyperextension
may occur in the athetoid or spastic hand with moderate or severe swan-neck
deformity at the 'opening' phase of prehension. The patient's complaints are of
complete or incomplete locking that may require passive assistance to initiate
PIPJ flexion. Surgical procedures to overcome this include rerouting the lateral
band, stabilisation or reconstruction procedure for the volar instability of the
PIPJ, etc. Volar stabilisation may be achieved by Flexor digitorum superficialis
(FDS) tenodesis procedures or criss-cross tendon graft for volar plate
reconstruction. We report a case of successful stabilisation using the criss
cross tendon sling procedure for volar plate reconstruction using a slip of the
FDS tendon instead of a free tendon graft. This is a simple and safe procedure
that effectively corrects the swan-neck deformity and improves the prehension
function in the hand.
PMID- 28506154
TI - Seroadaptive Strategies of Vancouver Gay and Bisexual Men in a Treatment as
Prevention Environment.
AB - British Columbia's treatment as prevention policy has provided free access to
highly active antiretroviral therapy (HAART) to all HIV-positive provincial
residents since 1996. One outcome is an increase in HIV-positive gay and bisexual
men (GBM) with suppressed viral loads. Previous cross-sectional analyses
indicated that some Vancouver GBM now recognize condomless anal sex with men on
HAART who report a suppressed viral load as a seroadaptive strategy. To test the
hypothesis that this new strategy, termed viral load sorting (VLS), is recognized
and used among by GBM in the Momentum Health Study, we analyzed longitudinal data
for HIV-negative/unknown (n = 556) and HIV-positive (n = 218) serostatus
participants. Analyses indicated that both groups reported VLS, and that
serostatus and Treatment Optimism Scale scores were significant determinants in
frequency and use. Results exemplify the medicalization of sex and Rogers'
Diffusion Of Preventative Innovations Model, and they have important implications
for HIV research and GBM sexual decision-making.
PMID- 28506158
TI - Incidence of Carpal Coalition in an Asian Population - Preliminary Findings of a
Study on Patients from a Distal Radius Fracture Database.
AB - BACKGROUND: Congenital carpal coalition is usually seen as an incidental finding.
The incidence of carpal coalition has been reported from 0.1 to 9.5 %; highest
incidence has been reported in people of African descent. The purpose of our
study is to evaluate the incidence and subtypes of carpal coalition in an Asian
population. METHODS: Review of the radiographs of the patients in our distal
radius fracture database from 2009 to 2014 was conducted to determine the
incidence and type of carpal coalition. RESULTS: 4141 patients' wrist radiographs
were reviewed. 2 cases of carpal coalition were identified; this leads to an
incidence of 0.048%. One was of luno-triquetral type and the other was of capito
hamate type. CONCLUSIONS: The preliminary results of our study indicate that
carpal coalition in the Asian population is less common than that reported in the
Western literature. Our results are inconclusive as to the type of carpal
coalition that is more common.
PMID- 28506157
TI - Motor and Sensory Cortical Changes after Contralateral Cervical Seventh Nerve
Root (CC7) Transfer in Patients with Brachial Plexus Injuries.
AB - BACKGROUND: Previous animal studies demonstrated that the sensory and motor
functions in ipsilesional upper limbs that had been reconstructed by CC7 transfer
eventually associated with the contralesional brain cortices that had originally
mediated the functions of the ipsilesional upper limbs before brachial plexus
injury (BPI). Our hypothesis was that the same findings would be seen in humans.
METHODS: Four patients with total BPI treated with CC7 transfer were included.
Changes in the locations of the activated areas in the primary motor (M1) and
somatosensory (S1) cortices corresponding to the motor outputs to and sensory
inputs from the ipsilesional limbs were investigated using functional near
infrared spectroscopy (fNIRS) 2-3 years and 6-7 years after surgery. RESULTS: One
patient was excluded from the evaluation of motor function after CC7 transfer.
The motor and sensory functions of the ipsilesional upper limb in all patients
were still controlled by the ipsilesional brain hemisphere 2-3 years after CC7
transfer. The reconstructed motions of the ipsilesional upper limbs correlated
with the contralesional M1 in one patient and the bilateral M1s in another
patient (both of whom demonstrated good motor recovery in the ipsilesional upper
limbs) and with the ipsilesional M1 in a third patient with poor motor recovery
in the ipsilesional upper limb. Sensory stimulation of the ipsilesional hands 6-7
years after CC7 transfer activated the contralesional S1 in two patients who
achieved good sensory recovery in the ipsilesional hands but activated the
ipsilesional S1 in the other two patients with poor sensory recovery of the
ipsilesional hands. CONCLUSIONS: Transhemispheric transposition of the activated
brain cortices associated with the recovery of motor and sensory functions of the
ipsilesional upper limbs was seen in patients with CC7 transfer as has been
reported for animal models of CC7 transfer.
PMID- 28506159
TI - Progression from Injection to Surgery for Trigger Finger: A Statistical Analysis.
AB - BACKGROUND: The purpose of this study was to identify predictive factors of poor
response to intra-flexoral sheath corticosteroid injection, as well as to
identify factors associated with patients' decisions to undergo surgical
treatment. METHODS: Data from 112 patients who received steroid injection
treatment for trigger finger were reviewed retrospectively. Logistic regression
was used to assess the prognostic value of factors assumed to affect prognosis
(age, sex, underlying disease, history of illness, presence of carpal tunnel
syndrome, multiple digit involvement, and pre- and post-operative disability
scores). RESULTS: Multiple digits were affected in 42 patients. Associated and
underlying conditions were carpal tunnel syndrome (n = 36), hypertension (n =
23), hyperlipidemia (n = 14), and history of malignant tumor (n = 10). Logistic
regression analysis showed that multiple digit involvement and Froimson clinical
severity score were factors significantly associated with surgical treatment
after intra-flexoral sheath corticosteroid injection treatment. These two factors
were also found to be associated with the patients' decisions to undergo surgical
treatment. CONCLUSIONS: Although local corticosteroid injection is useful in most
cases, providers need to counsel patients with multiple digit involvement and/or
severe cases about the possibility of requiring additional surgical treatment.
PMID- 28506160
TI - The Effect of Psychological Factors on the Outcomes of Carpal Tunnel Release: A
Systematic Review.
AB - BACKGROUND: Several studies report that psychological factors are associated with
outcomes of carpal tunnel release. However, interpretation of the association is
difficult as there are diverse outcome parameters and patient expectations are
different. We performed a systematic review to assess the relationships between
psychological factors and the various outcome parameters. METHODS: We identified
611 papers and selected 8 papers that fit the inclusion criteria. Psychological
factors assessed were anxiety, depression, pain catastrophizing, coping, and
mental health status. Outcomes of interest included satisfaction and measures of
perceived level of function, pain, and physical measures of recovery. RESULTS:
For satisfaction and perceived level of function as the outcome, three studies
reported a significant association, one study found an association approaching a
value of significance, and one study reported no association. For pain as the
outcome, two studies reported a significant association. For physical measures,
one study reported no association. CONCLUSIONS: This systematic review found that
depression correlates with postoperative pain, but that the association is less
clear between psychological factors and outcomes such as satisfaction, perceived
level of symptom and function, and physical measures of recovery. As pain may not
be a primary symptom or outcome of CTS, we consider that the current literature
does not strongly support the association between psychological factors and
outcomes of CTR. This review could be of benefit during preoperative counseling
in patients with psychological disturbances.
PMID- 28506161
TI - Symmetric Peripheral Running Sutures are Superior to Asymmetric Peripheral
Running Sutures for Increasing the Tendon Strength in Flexor Tendon Repair.
AB - BACKGROUND: The fatigue strength of three peripheral suture techniques for flexor
tendon repair was compared by cyclic loading of the repairs in the porcine flexor
digitorum tendon. METHODS: Thirty-six tendons were sutured using only peripheral
sutures with 6-0 Nylon. An initial cyclic load of 10 N for 500 cycles was applied
and increased by 10 N for an additional 500 cycles at each new load until
rupture. RESULTS: The fatigue strength of the symmetric running peripheral suture
was 85.0% and 144.8% greater than that of the two kinds of the asymmetric running
peripheral sutures. CONCLUSIONS: Symmetric running sutures can enhance the suture
strength and appears to be a useful technique for increasing the strength of the
peripheral suture.
PMID- 28506162
TI - Brodie's Abscess of the Radius in a Child.
AB - We herein report an unusual case of Brodie's abscess of the radius in a child. A
13-year-old boy presented with pain on his right distal forearm. A plain
radiograph showed an 8 cm translucent lesion in the distal radius. MRI showed a
penumbra sign on the T1-weighted image, hyperintensity on T2-weighted images, and
ring enhancement on the contrast-enhanced T1 image. 18F-FDG PET/CT images showed
an uptake at the margin of the radius. Curettage and iliac cancellous bone
grafting were undertaken for Brodie's abscess. Bacteriological examinations were
found to be negative, however, the pathologic diagnosis showed chronic
osteomyelitis. Eight months after surgery, the patient was asymptomatic and there
was no sign of recurrence of infection. For Brodie's abscess in a child, thorough
debridement is mandatory in addition to cancellous bone grafting. Brodie's
abscess should be considered in the differential diagnosis of a patient who
presents with forearm pain and exhibit the radiolucent osteolytic lesion on
simple radiography.
PMID- 28506163
TI - The Outcome of Treatment of Flexor Sheath (seed) Ganglia by a Percutaneous
Partial Pulley Release.
AB - BACKGROUND: The aims of this study were to assess the safety and efficacy of a
technique of partial percutaneous pulley release. METHODS: A retrospective cohort
study was undertaken treating adults with seed ganglia with a percutaneous pulley
release. The patients were reviewed independently after a mean of 6 (range 6-36)
months. RESULTS: We treated 24 patients over a 3 year period. There were 14 women
and ten men. The mean age was 39 (range 17-65) years. We were able to assess 21
patients with long term follow up. There was complete resolution in 14 (2/3) and
partial resolution in four. The remaining three patients had persisting symptoms
and requested open surgical excision. Apart from local tenderness and failure of
resolution there were no complications of percutaneous pulley release.
CONCLUSIONS: Bursting or aspiration of flexor sheath ganglia appears to be the
best primary treatment. If the ganglion recurs, this study suggests a
percutaneous release is safe and will resolve the symptoms in most patients.
PMID- 28506164
TI - Screw Fixation and Autogenous Bone Graft for an Irreducible Distal Ulna Fracture
Associated with Distal Radius Fracture.
AB - Distal ulna fractures often occur with distal radius fractures, and their
treatment method is still controversial. We considered reduction of the distal
radio-ulnar joint (DRUJ) surface the most important factor when treating distal
ulna fractures accompanied by residual dislocation. We herein presented a patient
with a distal ulna fracture accompanied by dislocation of the DRUJ surface in
whom an autogenous bone fragment collected from the radius was grafted onto the
ulnar bone defect after open reduction and Herbert screw fixation. In this
technique, the bone fragment was supported through the medullary cavity by
inserting a Herbert screw, which was less likely to cause irritation between the
screw and surrounding tissue, because the screw was almost entirely present in
the bone. In addition, an autogenous bone graft from the same surgical field may
be less invasive than that from another region.
PMID- 28506165
TI - Cold Welding in a Trapeziometacarpal Ball and Socket Prosthesis: A Case Report.
AB - While in revision hip surgery it has been described cold welding of the femoral
component in titanium implants, no previous reports have been published in TMC
prosthesis. We present a case report of a patient who sustained a TMC ARPE(r)
dislocation 11 months after surgery and during revision surgery, cold welding of
the neck with the metacarpal stem was observed. This may represent a problem when
revising this prosthesis and alternative procedures should be advised and
discussed with the patient when revising these implants.
PMID- 28506166
TI - Pacinian Corpuscles Neuroma. An Exceptional Cause of Pain in the Hand.
AB - Pacinian corpuscles are rapidly adapting mechanoreceptors mainly distributed in
the dermis of the fingers and palm of the hand. A neuroma of the Pacinian
corpuscle is a rare and extremely painful condition with a few cases reported in
the literature, most of them, associated with local or repetitive trauma. We
present a 71-year-old man with history of pain and swelling on his left index
without history of previous trauma initially diagnosed as tenosynovitis resistant
to conservative treatment in which we observed, directly in the subcutaneous
plane, spherical, gray and in clusters lesions closer to the collateral nerve
which were described by the pathological study as neuroma of the Pacinian
corpuscles.
PMID- 28506167
TI - Two-dimensional Morphological Characteristics of the Distal Radius on Axial
Magnetic Resonance Image and the Effects on Distal Screw Length.
AB - BACKGROUND: Detection of dorsal cortical penetration of distal locking screws is
difficult owing to the irregular shape of the dorsal surface of the distal
radius. This study was designed to analyze two-dimensional morphological
characteristics of the distal radius on axial magnetic resonance image, and to
suggest a guideline for evaluation of screw length in distal radius fractures on
the fluoroscopic or plain X-ray true lateral image. METHODS: Anteroposterior
length and lateral width of the distal radius, distance between the highest and
the lowest point of the dorsal cortex (deceptive length), and widths of the first
to second (hazard zone) and the third to fifth extensor compartments (safe zone)
at the Lister tubercle level were measured on 104 axial magnetic resonance images
by two hand surgeons. RESULTS: The mean length and width of the distal radius at
the Lister tubercle level were 22.96 mm and 30.42 mm, respectively. The mean
hazard zone and safe zone widths were 8.72 mm and 19.43 mm, respectively. The
mean deceptive length was 4.07 mm and the deceptive length did not have a
relationship with height, sex, and age of subjects. CONCLUSIONS: We suggest that
4 mm be used as a reference value for the evaluation screw length at the safe
zone. If the vertical distance between a distal screw tip and the peak of the
Lister tubercle is lesser than 4 mm on a fluoroscopic or plain X-ray true lateral
image, dorsal cortical penetration should be suspected. When dorsal cortical
penetration at the hazard zone is suspected, both oblique or pro-supination views
should be checked.
PMID- 28506168
TI - Trigger Finger: An Atraumatic Medical Phenomenon.
AB - Trigger finger is a mechanical problem with many etiological factors as possible
causes, such as diabetes mellitus, carpal tunnel syndrome and repetitive finger
movements. Although it can afflict anyone, it is much commoner in middle-aged
women than men and the most commonly involved digit is reported to be the thumb.
The diagnosis is mainly based on clinical symptoms during examination and first
line treatment is conservative with splinting and corticosteroid injections.
Surgical open release is the "gold standard" of trigger finger treatment because
it allows more careful inspection of the surgical area and is highly effective
with low complication rates.
PMID- 28506169
TI - Painful Snapping of Thumb Caused by Osteochondroma of Trapezium.
AB - Osteochondroma is the most common benign bone tumor. Lesions occurring at the
carpal bones are extremely rare. There are very few cases of osteochondroma at
the trapezium had been reported in the English literature. We reported a 47-year
old patient with an osteochondroma of the left trapezium presented with painful
snapping of abductor pollicis longus tendon.
PMID- 28506170
TI - Osteoid Osteoma of the Distal Phalanx of the Ring Finger with Clubbed Finger
Deformity: A Case Report.
AB - Osteoid osteoma of the distal phalanx is very rare. We describe a case of osteoid
osteoma of the distal phalanx of the ring finger with clubbed finger deformity
that improved after tumour removal. A 50-year-old left-handed man presented with
a history of right ring finger pain without any trauma. The distal phalanx of the
ring finger had tender, redness, and a clubbed finger deformity. Plain
radiography indicated a circular radiolucent area in the centre of the lesion.
Computed tomography and gadolinium enhanced magnetic resonance imaging indicated
presence of a nidus. The lesion was removed via the transungual approach.
Histopathological examination confirmed the presence of an osteoid osteoma. His
pain was immediately relieved after surgery. At the 2-year followup, he had no
pain and the clubbed finger deformity had improved. In cases where clubbed finger
deformity involves only one finger, the possibility of chronic osteomyelitis or
osteoid osteoma should be considered.
PMID- 28506171
TI - A Protocol for Evaluation and Rehabilitation of Distal Radius Fractures Using
Sensorimotor Input: A Case Series.
AB - BACKGROUND: Proprioception and sensorimotor input are used to treat neurological
and joint injuries. Following distal radius fractures (DRF) there is a temporary
loss of proprioception that should be addressed. We created a protocol for
evaluation, and a treatment plan following wrist surgery that is based on
proprioceptive and sensorimotor input. We describe a series of patients
undergoing surgery for DRF that were evaluated and treated with these protocols.
METHODS: Both evaluation and treatment protocols included comprehensive
sensorimotor procedures performed with eyes open and closed. These included
Semmes- Weinstein, static and moving 2-point discrimination, vibration,
temperature testing, Moberg pick-up- test, stereognosis and proprioception.
RESULTS: A series of twelve patients was evaluated and treated with the protocol
following surgical treatment for DRF. Patients demonstrated significant
sensorimotor deficits, which improved utilizing the comprehensive sensorimotor
treatment protocol. CONCLUSIONS: Further study is necessary to validate the
results of this pilot series. Use of proprioception and sensorimotor input may
improve outcomes of rehabilitation following DRF.
PMID- 28506172
TI - The Effect of Myostatin (GDF-8) on Proliferation and Tenocyte Differentiation of
Rat Bone Marrow-Derived Mesenchymal Stem Cells.
AB - BACKGROUND: The future in flexor tendon surgery involves tissue engineering
approaches directed toward increasing early repair strength to accelerate tendon
healing and to allow for earlier onset of rehabilitation. Previous work has shown
that pluripotential mesenchymal stem cells may be successfully delivered to a
tendon repair site using a suture carrier. The current work describes the use of
Myostatin (GDF-8) to help guide these delivered pluripotential stem cells to
differentiate down a tenocyte lineage to potentially maximize the reparative
effects of these cells at the tendon repair site. METHODS: Primary rat bone
marrow mesenchymal stem cells isolated from the long bones of male Sprague-Dawley
rats were treated with 500 ng/ml myostatin for 24 h, 48 h, and 72 h. Collagen 1
A, scleraxis (Scx), and tenomodulin (Tnmd) expression, indicative of tenogenesis,
was analyzed using real time PCR and immunohistochemistry staining. A migration
assay was performed to assess the functional activity of BMSCs after they were
treated with myostatin. RESULTS: Compared to the control cells (without
treatment), the cells treated with 500 ng/ml myostatin for 72 h exhibited higher
expression of Col 1A, Scx, and Tnmd. The mRNA expression of Col1A, Scx, Tnmd
increased 15.3, 13 and 7 times respectively. Immunohistochemistry staining showed
Scx and Tnmd were expressed in the cellular cytoplasm. In response to myostatin,
the cells also showed a tendency to proliferate and migrate more than the control
cells. CONCLUSIONS: Myostatin (GDF-8) has the ability to increase rat bone marrow
mesenchymal stem cell growth and differentiation toward a tenocyte lineage. This
information could be useful for future studies regarding tendon repair.
PMID- 28506173
TI - That Tendon is the Median Nerve: Perils of a Palmaris Longus Deficient Wrist.
AB - BACKGROUND: To document the course of the median nerve in the distal forearm in
palmaris longus (PL) deficient forearms and elucidate features that help
distinguish it from the PL. METHODS: In the cadaveric study, 56 cadaveric
forearms were dissected and the location and course of the median nerve were
documented. In the clinical study, 20 healthy subjects with absent PL were
examined with provocative tests to elucidate the PL (Schaeffer's test and
Thompson's test), and modified Durkan's and Phalen's tests. In the imaging study,
one subject with a clearly visible and palpable median nerve was further
evaluated with MRI with a superficial fiducial marker. RESULTS: Cadaveric
dissection revealed that the median nerve was deep to the antebrachial fascia and
superficial to the FDS tendons in the distal forearm. In 9 specimens without a
PL, the median nerve was the most superficial structure deep and lay draped over
the FDS tendons. In the clinical study, PL absence was bilateral in 4 subjects
and unilateral in 16. The nerve was visible and palpable in 4 forearms and
palpable but not visible in 20 forearms. In all 24 forearms, the nerve was
palpable as a lax, mobile, cord-like structure that could be rolled over the taut
FDS tendons. Tinel's and Durkan's signs were positive in 11 subjects. In the
imaging study, MRI confirmed that the palpable structure was the median nerve.
CONCLUSIONS: Unlike the PL, the nerve is non-contractile and remains flaccid on
provocative testing. It is usually palpable and may also be visible in thin
forearms. Careful scrutiny may reveal it to be distinct from, and draped over
underlying FDS tendons. These findings may help avoid inadvertent median nerve
harvest in place of a PL tendon graft.
PMID- 28506174
TI - X-ray Guided Steroid Injections for Proximal Interphalangeal Joint Osteoarthritis
of the Fingers.
AB - BACKGROUND: Osteoarthritis of the finger proximal interphalangeal joints (PIPJ's)
is common and severely limits hand function. Intra-articular steroid injections
are frequently used, but there is little research assessing this treatment
option. METHODS: This was a prospective audit of patients undergoing intra
articular steroid injections into the PIPJ under image intensifier guidance. The
aims were to assess the duration of pain relief, hand function and range of
movement following this procedure. Fifty injected joints were followed up at six
weeks, three and six months. RESULTS: There were significant improvements in both
pain scores and the range of movement for up to three months. Analgesia
requirements decreased and hand function improved up to three months. By six
months, patients were approaching their preinjection scores. CONCLUSIONS: X-ray
guided injections are a simple procedure which can be effectively performed in
the out- patient setting, resulting in satisfied patients with improved hand
function and pain scores.
PMID- 28506175
TI - Corrective Step-cut Osteotomy at the Affected Bone for Correction of Rotational
Deformity Due to Fracture of the Middle Phalanx.
AB - Malunion at the shaft of the middle phalanx yields less functional problems
compared with malunion at the shaft of the proximal phalanx and metacarpal bones.
In the present report, the patient sustained a minimally displaced fracture at
the distal portion of the distal middle phalanx of the ring finger spraining the
finger during playing flag football. Fracture was treated conservatively and
fracture union was completed. However, the patient complained of functional
problems in activities of daily living due to the malrotational deformity of the
finger. We treated the malrotational deformity close to the distal
interphalangeal joint of the middle phalanx with step-cut osteotomy at the
affected bone successfully.
PMID- 28506176
TI - Neurolysis with Amniotic Membrane Nerve Wrapping for Treatment of Secondary
Wartenberg Syndrome: A Preliminary Report.
AB - BACKGROUND: Entrapment of the superficial sensory branch of the radial nerve
(SRN) commonly results in debilitating pain of the dorsoradial wrist. Symptom
relief following SRN neurolysis is often incomplete or temporary due to recurrent
perineural scarring. METHODS: We performed a retrospective review with
prospective follow-up of all patients with SRN neuropathy who were treated with
neurolysis and nerve wrapping using an amnion-based allograft adhesion barrier
over a one-year interval. Measured outcomes included pain rated by Visual Analog
Scale (VAS) and Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH)
functional outcome scores. RESULTS: Three females satisfied inclusion. At mean
follow-up of 28.9 months, all three patients exhibited improved pain (mean VAS
change -4.7 +/- 0.6), function (mean QuickDASH change -40 +/- 5), and subjective
satisfaction. No adverse events or reactions to the implanted tissue occurred.
CONCLUSIONS: SRN entrapment neuropathy was safely and effectively treated with
neurolysis and amnion nerve wrapping in this small series. Use of this technique
for perineural scar prevention warrants additional study in larger groups of
patients and in other upper extremity entrapment neuropathies.
PMID- 28506177
TI - Metastasis of Renal Cell Carcinoma to the Trapezium.
AB - Solitary metastasis of a carcinoma to carpal bone is extremely rare. Metastases
of renal cell carcinoma (RCC) usually occur in a multiple fashion and there has
been no report to date of a solitary metastasis to trapezium from RCC. The tumor
was excised and reconstructed with iliac bone transplantation. 2 years and 6
months after surgery, there is no local recurrence with minimal functional loss.
PMID- 28506178
TI - Galeazzi-equivalent Fractures: Report of Two Cases and Literature Review.
AB - The Galeazzi-equivalent fracture is a rare injury that occurs in children. The
most important issue is the distal ulnar epiphyseal injury. Although there have
been some case reports, most of them performed only short term follow-up. This
article describes two cases of this fracture with long term follow-up until
epiphyseal closure. First case is a 12-year-old girl who sustained a
Galeazziequivalent fracture of her right forearm and underwent emergency surgery.
At follow-up of 5 years and 10 months postsurgery, radiographs show ulnar growth
arrest of one mm and she has mild pain. Second case is a 15-year-old boy who
sustained an open Galeazzi-equivalent fracture of his left forearm and underwent
emergency surgery. At follow-up of 3 years and 3 months postsurgery, radiographs
show no growth arrest of the distal ulna. He has no residual complaint. Long term
follow-up is absolutely necessary to monitor ulnar growth.
PMID- 28506179
TI - Value of Soft Tissue Release Procedure around the Shoulder to Improve Shoulder
Abduction in Birth Brachial Plexus Palsy and Analysis of the Factors Affecting
Outcome.
AB - BACKGROUND: A lack of shoulder abduction in spontaneously recovered birth
brachial plexus palsy (BBPP) is a common presentation. We have performed a soft
tissue release operation in these patients to remove the tethering effect of the
tight and cocontracting shoulder adductors. This study was undertaken in order to
assess the outcome of this surgical procedure. METHODS: We performed a
retrospective analysis of 120 patients who displayed spontaneous recovery from
BBPP and subsequently underwent soft tissue release procedure to improve shoulder
abduction. The operation involved release of the pectoralis major, latissimus
dorsi (LD) and teres major (TM) with axillary nerve neurolysis and transfer of LD
and TM to teres minor at a lower position. Outcomes were assessed at a minimum
follow up of two years. The primary outcome measures were range of shoulder
abduction and Mallet score. Parents were interviewed and their satisfaction was
graded on a Likert scale. We also explored prognostic factors responsible for
better outcomes namely, age at operation, extent of involvement; preoperative
shoulder abduction range, internal rotation deformity, triceps power and Mallet
score. RESULTS: The average patient age was 5.8 years(range 1-17). Follow up
ranged from 2-6 years. Average preoperative shoulder abduction was 85 degrees
(range 30 degrees -140 degrees ). Postoperatively the average shoulder abduction
was 161 degrees (range 80 degrees -180 degrees ). The mean improvement in
abduction was 76 degrees (range 20 degrees -110 degrees ) [p < 0.001]. Mallet
score improved from 16.4 to 19.5 (p < 0.001). High parental satisfaction was
recorded by Likert scale assessment. Regression analysis indicated a favourable
outcome in patients who are younger, have a better preoperative abduction range
and a preoperative triceps power > grade 3. CONCLUSIONS: Soft tissue release
procedure employed in this series is effective in improving shoulder abduction.
Patients who are of younger age, have better preoperative abduction and triceps
power of > grade 3 are expected to achieve the best outcome.
PMID- 28506180
TI - Midterm Follow-up of Treating Volar Marginal Rim Fractures with Variable Angle
Lcp Volar Rim Distal Radius Plates.
AB - BACKGROUND: Specific treatment of the volar marginal rim fragment of distal
radius fractures avoids occurance of volar radiocarpal dislocation. Although
several fixation systems are available to capture this fragment, adequately
maintaining internal fixation is difficult. We present our experience of the
first 10 cases using the 2.4 mm variable angle LCP volar rim distal radius plate
(Depuy Synthes(r), West Chester, US), a low-profile volar rim-contouring plate
designed for distal plate positioning and stable buttressing of the volar
marginal fragment. METHODS: Follow-up patient satisfaction, range of motion,
grips strength, functional scoring with the QuickDASH and residual pain with a
numeric rating scale were assessed. Radiological evaluation consisted in
evaluating fracture consolidation, ulnar variance, volar angulation and
maintenance of the volar rim fixation. RESULTS: The female to male ratio was 5:5
and the mean age was 52.2 (range, 17-80) years. The mean follow-up period was 11
(range, 5-19) months postoperatively. Patient satisfaction was high. The mean
total flexion/extension range was 144 degrees (range, 100-180 degrees ) compared
to the contralateral uninjured side 160 degrees (range, 95-180 degrees ). The
mean total pronation/supination range was 153 degrees (range, 140-180 degrees )
compared to the contralateral uninjured side 170 degrees (range, 155-180 degrees
). Mean grip strength was 14 kg (range, 9-22), compared to the contralateral
uninjured side 20 kg (range, 12-25 kg). Mean pre-injury level activity QuickDASH
was 23 (range, 0-34.1), while post-recovery QuickDASH was 25 (range 0-43.2).
Residual pain was 1.5 on the visual numerical pain rating scale. Radiological
evaluation revealed in all cases fracture consolidation, satisfactory
reconstruction of ulnar variance, volar angulation and volar rim. We encountered
no flexor tendon complications, although plate removal was systematically
performed after fracture consolidation. CONCLUSIONS: The 2.4 mm variable angle
LCP volar rim distal radius plates is a valid treatment option for treating the
volar marginal fragment in distal radius fractures.
PMID- 28506181
TI - Intersectionality in the Lives of LGBTQ Youth: Identifying as LGBTQ and Finding
Community in Small Cities and Rural Towns.
AB - This article presents an analysis of the views of younger bisexual and lesbian
women and transgender youth living in a western Canadian small city on their
sexual and gender identities. Data were collected through focus groups and
interviews and analyzed thematically through an intersectional lens. The
purposive sample was composed of 13 youth who identified as lesbian, gay,
bisexual, transgender, or queer (LGBTQ) and whose average age was 19.8 years. The
analytical themes of (1) living in a small town, (2) identifying and being
identified, and (3) talking intersectionality indicate that the sexual identities
and gender identities and expressions of LGBTQ youth change across time and
context and are impacted by often overlooked factors including faith, Indigenous
ancestry, disability, and class. Further, the size and character of the community
significantly impacts LGBTQ youth identity development and expression. This
research demonstrates the uniqueness of individual youth's experiences-opposing
notions of milestone events as singularly important in queer youth identity
development.
PMID- 28506182
TI - Elemental properties of copper slag and measured airborne exposures at a copper
slag processing facility.
AB - In 1974, the National Institute for Occupational Safety and Health recommended a
ban on the use of abrasives containing >1% silica, giving rise to abrasive
substitutes like copper slag. We present results from a National Institute for
Occupational Safety and Health industrial hygiene survey at a copper slag
processing facility that consisted of the collection of bulk samples for metals
and silica; and full-shift area and personal air samples for dust, metals, and
respirable silica. Carcinogens, suspect carcinogens, and other toxic elements
were detected in all bulk samples, and area and personal air samples. Area air
samples identified several areas with elevated levels of inhalable and respirable
dust, and respirable silica: quality control check area (236 mg/m3 inhalable;
10.3 mg/m3 respirable; 0.430 mg/m3 silica), inside the screen house (109 mg/m3
inhalable; 13.8 mg/m3 respirable; 0.686 mg/m3 silica), under the conveyor belt
leading to the screen house (19.8 mg/m3 inhalable), and inside a conveyor access
shack (11.4 mg/m3 inhalable; 1.74 mg/m3 respirable; 0.067 mg/m3 silica). Overall,
personal dust samples were lower than area dust samples and did not exceed
published occupational exposure limits. Silica samples collected from a plant
hand and a laborer exceeded the American Conference of Governmental Industrial
Hygienist Threshold Limit Value of 0.025 ug/m3. All workers involved in copper
slag processing (n = 5) approached or exceeded the Occupational Safety and Health
Administration permissible exposure limit of 10 ug/m3 for arsenic (range: 9.12
18.0 ug/m3). Personal total dust levels were moderately correlated with personal
arsenic levels (Rs = 0.70) and personal respirable dust levels were strongly
correlated with respirable silica levels (Rs = 0.89). We identified multiple
areas with elevated levels of dust, respirable silica, and metals that may have
implications for personal exposure at other facilities if preventive measures are
not taken. To our knowledge, this is the first attempt to characterize exposures
associated with copper slag processing. More in-depth air monitoring and health
surveillance is needed to understand occupational exposures and health outcomes
in this industry.
PMID- 28506183
TI - Strategies and challenges for communicating the diagnosis of cancer in cross
cultural clinical settings-Perspectives from South African healthcare
professionals.
AB - Communicating the diagnosis of cancer in cross-cultural clinical settings is a
complex task. This qualitative research article describes the content and process
of informing Zulu patients in South Africa of the diagnosis of cancer, using
osteosarcoma as the index diagnosis. We used a descriptive research design with
census sampling and focus group interviews. We used an iterative thematic data
analysis process and Guba's model of trustworthiness to ensure scientific rigor.
Our results reinforced the use of well-accepted strategies for communicating the
diagnosis of cancer. In addition, new strategies emerged which may be useful in
other cross-cultural settings. These strategies included using the stages of
cancer to explain the disease and its progression and instilling hope using a
multidisciplinary team care model. We identified several patients, professionals,
and organizational factors that complicate cross-cultural communication. We
conclude by recommending the development of protocols for communication in these
cross-cultural clinical settings.
PMID- 28506184
TI - Complications of Psychotropic and Pain Medications in an Ultrarapid Metabolizer
Patient at the Upper 1% of Cytochrome P450 (CYP450) Function Quantified by
Combinatorial CYP450 Genotyping.
AB - A 44-year-old Caucasian woman presented with a history of empirical treatment
with 20 pain and psychotropic medications, as well as dual comorbidity of
intractable pain and depression. A multiple gain-of-function profile in the
CYP450 family of cytochrome P450 (CYP450) drug metabolism isoenzymes was
discovered. The patient was a homozygote of suprafunctional alleles for both
CYP2D6 (*35/*35) and CYP2C19 (*17/*17) genes and functional alleles for CYP2C9
(*1/*1), which account for aggregate drug metabolism function at the upper 1% of
the population. The patient improved clinically with discontinuation of
psychotropics and pain medications that were substrates of CYP2D6 and/or CYP2C19,
suggesting that much of her symptomatology was drug induced. Combinatorial
genotyping of CYP450 genes is diagnostically useful in individuals with histories
of multiple side effects or drug resistance, which could be avoided by
genetically informed therapeutics in behavioral health.
PMID- 28506185
TI - The cascading influence of multisensory processing on speech perception in
autism.
AB - It has been recently theorized that atypical sensory processing in autism relates
to difficulties in social communication. Through a series of tasks concurrently
assessing multisensory temporal processes, multisensory integration and speech
perception in 76 children with and without autism, we provide the first
behavioral evidence of such a link. Temporal processing abilities in children
with autism contributed to impairments in speech perception. This relationship
was significantly mediated by their abilities to integrate social information
across auditory and visual modalities. These data describe the cascading impact
of sensory abilities in autism, whereby temporal processing impacts multisensory
information of social information, which, in turn, contributes to deficits in
speech perception. These relationships were found to be specific to autism,
specific to multisensory but not unisensory integration, and specific to the
processing of social information.
PMID- 28506186
TI - Response to Letter to the Editor: Confounding by Symptomatic Mefloquine Exposure
in Military Studies of Post-Traumatic Stress Disorder.
PMID- 28506188
TI - Corrigendum.
PMID- 28506187
TI - Ten-Year Changes in Healthy Eating Attitudes in the SUN Cohort.
AB - OBJECTIVE: The objective of this study was to assess the within-subject
longitudinal changes in self-perceived healthy eating attitudes after 10 years of
follow-up and to identify predictors of long-term changes in a middle-aged adult
cohort. METHODS: Four thousand five hundred seventy-two participants completed a
validated food frequency questionnaire (FFQ) at baseline and after 10 years of
follow-up. The FFQ was expanded with a brief 10-item questionnaire about eating
attitudes with 2 possible answers: yes or no. A baseline score and a 10-year
score were calculated with these 10 items (range from 0 to 10). Participants were
categorized into 3 groups according to this score. Linear and logistic
regressions were used to examine changes at follow-up and associations between
baseline characteristics and improvement in the score. RESULTS: After 10 years of
follow-up, a statistically significant favorable change (p < 0.001) was achieved
in all questions about eating attitudes, particularly in these items: "Do you try
to eat less sweets and pastries?" (12%), "Do you try to eat less meat?" (11.1%),
and "Do you try to reduce your fat intake?" (10%). Being female (odds ratio [OR]
= 1.19, 95% confidence interval [CI], 1.02-1.39), being 35-50 or >= 50 years old
(OR = 1.24, 95% CI, 1.07-1.44 and OR = 1.74, 95% CI, 1.38-2.18, respectively), a
high level of physical activity (OR for third vs first tertile = 1.20, 95% CI,
1.02-1.41), and a higher Mediterranean diet score (OR for second and third
tertiles = 1.18, 95% CI, 1.01-1.37 and OR = 1.26, 95% CI, 1.04-1.52,
respectively) were associated with a higher probability of improving the eating
attitudes score, while a low body mass index (BMI; OR = 0.71, 95% CI, 0.51-1.00)
and snacking between meals (OR = 0.84, 95% CI, 0.73-0.97) were associated with a
lower probability of improving their score. CONCLUSIONS: The eating attitudes of
the participants in the Seguimiento Universidad de Navarra (SUN) cohort became
more favorable after 10 years of follow-up. Certain sociodemographic or clinical
variables may predict a positive change.
PMID- 28506190
TI - Comparison of Blood Glucose Monitoring Systems for Use in Insulin Clamp Studies
During Either Intralipid or Glycerol Co-infusions.
PMID- 28506189
TI - Conducting Biobehavioral Research in Patients With Advanced Cancer: Recruitment
Challenges and Solutions.
AB - Despite significant advances in cancer treatment and symptom management
interventions over the last decade, patients continue to struggle with cancer
related symptoms. Adequate baseline and longitudinal data are crucial for
designing interventions to improve patient quality of life and reduce symptom
burden; however, recruitment of patients with advanced cancer in longitudinal
research is difficult. Our purpose is to describe challenges and solutions to
recruitment of patients with advanced cancer in two biobehavioral research
studies examining cancer-related symptoms. Study 1: Symptom data and peripheral
blood for markers of inflammation were collected from newly diagnosed patients
receiving chemotherapy on the first day of therapy and every 3-4 weeks for up to
6 months. Study 2: Symptom data, blood, and skin biopsies were collected from
cancer patients taking epidermal growth factor receptor inhibitors at specific
time points over 4 months. Screening and recruitment results for both studies are
summarized. Timing informed consent with baseline data collection prior to
treatment initiation was a significant recruitment challenge for both the
studies. Possible solutions include tailoring recruitment to fit clinic needs,
increasing research staff availability during clinic hours, and adding
recruitment sites. Identifying solutions to these challenges will permit the
conduct of studies that may lead to identification of factors contributing to
variability in symptoms and development of tailored patient interventions for
patients with advanced cancer.
PMID- 28506191
TI - Use of the Neuropsychiatric Inventory to Characterize the Course of
Neuropsychiatric Symptoms in Progressive Supranuclear Palsy.
AB - The aim of this study was to determine the neuropsychiatric profile in a cohort
of progressive supranucelar palsy (PSP) patients and their dynamic changes over a
follow-up period of 1 year. A total of 59 patients were assessed at baseline,
while 25 of them were accessible after 1 year of the follow-up. The most common
symptoms were apathy and depression, which were also found to be, among other
variables, the independent determinants of increased Neuropsychiatric Inventory
(NPI) total score. Moreover, apathy deteriorated most profoundly over the follow
up period. The NPI seemed to be a sensitive measure of behavioral changes in PSP.
PMID- 28506192
TI - The Expanding Prominence of Toxic Leukoencephalopathy.
AB - Toxic leukoencephalopathy (TL) is a disorder of brain white matter caused by
exposure to leukotoxic agents. Magnetic resonance imaging (MRI) can readily
identify this syndrome, and, together with diffusion tensor imaging, MRI
continues to offer important insights into its nature. Since the first formal
description of TL in 2001, many new leukotoxic disorders have been recognized,
and the range of leukotoxins has expanded to include more therapeutic drugs,
drugs of abuse, and environmental insults. While the understanding of
pathophysiology remains incomplete, TL is increasingly common in clinical
practice, and the potential long-term cognitive sequelae of toxic white matter
injury merit attention.
PMID- 28506193
TI - Experiences of partners of prostate cancer survivors: A qualitative study.
AB - Prostate cancer, Australia's leading cancer, has treatment side effects that
reduce the quality of life for both survivors and partners. Limited partner
research exists. This study aimed to address this gap in the literature by
gathering data directly from partners to obtain a deeper understanding of their
experiences of prostate cancer survivorship that helps inform healthcare service
providers. A qualitative approach was taken to explore participant views (N = 16)
through three focus groups and two in-depth interviews. Five themes emerged
relating to caregiver burden, knowledge deficit, isolation, changes of sexual
relations, and unmet needs. Possible implications for practice may include the
need for specific partner-related information and interventions to assist couples
to cope with the emotional distress caused by treatment side effects.
PMID- 28506194
TI - The use of systemic therapies to prevent progression of inflammatory breast
cancer: which targeted therapies to add on cytotoxic combinations?
AB - INTRODUCTION: Inflammatory breast cancer is a rare but frequently fatal disease,
essentially because of its high ability to develop distant metastases. Even
though the prognosis of IBC was significantly improved by multimodal management,
including the systematic use of cytotoxic-based induction, the prognosis remains
largely dismal. Areas covered: This review presents the main achievements in the
systemic treatment of IBC during the past 30 years. It focuses more specifically
on recent results obtained with targeted therapies, including anti-HER2 and anti
angiogenic agents. Novel approaches under investigation are presented. Expert
commentary: Current management of IBC is subtype-specific and the largest benefit
has been achieved in HER2-positive disease. The identification of breakthrough
therapeutic advances is eagerly awaited and will require the development of IBC
specific clinical trials. Future clinical investigations should not only aim to
increase the pathological response rate but also to eradicate distant metastases,
which ultimately lead to patient death.
PMID- 28506196
TI - Sir William Harvey, Congenital Heart Disease and Anesthesia.
PMID- 28506197
TI - High-resolution mass spectrometry confirms the presence of a hydroxyproline (Hyp)
post-translational modification in the GGGGP linker of an Fc-fusion protein.
AB - Flexible and protease resistant (G4S)n linkers are used extensively in protein
engineering to connect various protein domains. Recently, several groups have
observed xylose-based O-glycosylation at linker Ser residues that yield unwanted
heterogeneity and may affect product quality. Because of this, an engineering
effort was implemented to explore different linker sequence constructs. Here, we
demonstrate the presence of an unexpected hydroxylation of a prolyl residue in
the linker, made possible through the use of high-resolution mass spectrometry
(HR-MS) and MSn. The discovery started with the detection of a poorly resolved
~+17 Da mass addition at the reduced protein chain level of an Fc-fusion
construct by liquid chromatography-MS. Upon further investigation at the peptide
level using HR-MS, the mass increase was determined to be +15.99 Da and was
localized to the linker peptide SLSLSPGGGGGPAR [210-223]. This peptide
corresponds to the C-terminus of Fc [210-216], the G4P linker [217-221], and
first 2 amino acids of a growth factor [222-223]. The linker peptide was first
subjected to MS2 with collision-induced dissociation (CID) activation. The
fragmentation profile localized the modification to the GGGPA [218-222] portion
of the peptide. Accurate mass measurement indicated that the modification is an
addition of an oxygen and cannot be CH4, thus eliminating several possibilities
such as Pro->Leu. However, other possibilities cannot be ruled out. Higher-energy
collision-induced dissociation (HCD)-MS2 and MS3 using CID/CID were both unable
to differentiate between Ala222-> Ser222 or Pro221-> Hyp221. Finally, MS3 using
high-resolution CID/HCD confirmed the mass increase to be a Pro221->Hyp221 post
translational modification.
PMID- 28506200
TI - Welcome note.
PMID- 28506201
TI - Abstracts for the 22nd Meeting of the European Society of Neurosonology and
Cerebral Hemodynamics (ESNCH), 19-21 May 2017, Berlin.
PMID- 28506198
TI - Naturally occurring benzoic acid derivatives retard cancer cell growth by
inhibiting histone deacetylases (HDAC).
AB - Histone deacetylases (HDACs), which modulate the expression of genes, are
potential therapeutic targets in several cancers. Targeted inhibition of HDAC
prevents the expression of oncogenes thereby help in the treatment of cancers.
Hence, several pharmaceutical companies developed inhibitors of HDAC and tested
them in preclinical models and in clinical trials. SAHA (suberanilohydroxamic
acid) is one such HDAC inhibitor developed for treating breast and colorectal
carcinomas. However, due to poor efficacy in clinical trials the utility of SAHA
for treating cancers was discouraged. Similarly another HDAC inhibitor
Trichostatin-A (TSA) also showed promising results in clinical trials but
exhibited severe adverse effects, which dampened the interest of using this
molecule for cancer treatment. Therefore, search for developing a potent HDAC
inhibitor with minimal side effects still continues. Hence, in this study we have
screened benzoic acid and benzoic acid derivatives with hydroxylic (-OH) groups
and methoxy (-OCH3) groups for their efficacy to bind to the TSA binding site of
HDAC using molecular docking studies. Molecules that showed much stronger
affinity (than TSA) to HDAC were tested for inhibiting HDAC expressing cultured
cancer cells. DHBA but not Dimethoxy Benzoic Acid (DMBA) inhibited HDAC activity,
leading to cancer cell growth inhibition through the induction of ROS and
cellular apoptosis mediated by Caspase-3. In addition, DHBA arrested cells in
G2/M phase of the cell cycle and elevated the levels of sub-G0-G1 cell
population. In summary, results of this study report that DHBA could be a strong
HDAC inhibitor and inhibit cancer cell growth more effectively.
PMID- 28506202
TI - Subtle and Severe: Microaggressions Among Racially Diverse Sexual Minorities.
AB - In recent years, understanding prejudice and discrimination toward minorities has
developed to include the investigation of microaggressions. Microaggressions are
brief and commonplace verbal, behavioral, or environmental indignities. They are
intentional or unintentional and communicate hostile, derogatory, or negative
slights toward racial and sexual minorities. The purpose of this phenomenological
study is to chronicle the prevalence and type of microaggressions experienced
among a sample of 18 highly educated and racially diverse sexual minorities, 24
65 years of age. The impact of microaggressions on physical and psychological
health is central to our investigation. Thematic data analysis was used to
analyze 14 interviews and one focus group, which resulted in the following themes
of microaggressions: (a) discomfort/disapproval with LGBT experience, (b)
assumption of universal experience, (c) traditional gender role stereotyping, (d)
denial of personal privacy, (e) exoticization, (f) ascription of intelligence,
(g) policing bodies, and (h) assumption of criminality. Research findings may
have implications for the development of interventions that can serve clinicians
in their therapeutic work with microaggressed sexual minorities across racial
diversity.
PMID- 28506203
TI - Optimization of Microemulsion Based Transdermal Gel of Triamcinolone.
AB - BACKGROUND: Triamcinolone is a long acting corticosteroid used in the treatment
of arthritis, eczema, psoriasis and similar conditions which cause inflammation.
Triamcinolone has half-life of 88min. Prolonged oral use is associated with
gastrointestinal adverse effects as peptic ulcer, abdominal distention and
ulcerative esophagitis as described in various patents. Microemulgel offers
advantage of better stability, better loading capacity and controlled release
especially for drug with short half life. OBJECTIVE: Objective of the present
study was to optimize microemulgel based transdermal delivery of triamcinolone.
METHOD: Saturated solubility of triamcinolone in various oils, surfactants and co
surfactants is estimated. Pseudo-ternary phase diagrams were constructed to
determine the region of transparent microemulsion. Microemulsion was evaluated
for globule size (FE-SEM, zetasizer), % transmittance, pH, viscosity,
conductivity etc. Design of experiment was used to optimize microemulsion based
gel. Carbopol 971P and HPMC K100M were used as independent variables.
Microemulsion based gel was evaluated for in-vitro as well as ex-vivo parameters.
RESULTS: Microemulsion was formulated with oleic acid, lauroglycol FCC and
propylene glycol. PDI 0.197 indicated microemulsion is mono-disperse. 32
factorial design gave batch F8 as optimized. Design expert suggested drug
release; gel viscosity and bio-adhesive strength were three significant dependant
factors affecting the transdermal delivery. F8 showed drug release 92.62.16+/
1.22% through egg membrane, 95.23+/-1.44% through goat skin after 8hr and
Korsmeyer-Peppas release model was followed. CONCLUSION: It can be concluded that
a stable, effective controlled release transdermal microemulgel was optimised for
triamcinolone. This would be a promising tool to deliver triamcinolone with
enhanced bioavailability and reduced dosing frequency.
PMID- 28506204
TI - Antibiotic Effects of Loperamide: Homology of Human Targets of Loperamide with
Targets in Acanthamoeba spp.
AB - BACKGROUND: Loperamide is an anti-diarrheal drug prescribed for non-infectious
diarrhea. The drug is an opioid receptor agonist, blocker of voltage-dependent
calcium channel (Cav) and calmodulin (CaM) inhibitor on human cells. Loperamide
has been reported to exert anti-amoebic effects against pathogenic strains of
Acanthamoeba castellanii. OBJECTIVES: The precise mode of antibiotic action,
cellular target homology with human counterparts and the pattern of cell death
induced by loperamide in Acanthamoeba castellanii remain to be established.
Additionally, we attempt to establish the presence a primitive Cav in
Acanthamoeba castellanii. METHODS: Bioinformatics, 3D structural modelling,
ligand binding predictions and apoptotic/ amoebicidal assays were used in this
study to answer the above queries. Amino acid sequences and structural models
were compared between human and A. castellanii proteins that are involved in the
regulation of calcium (Ca+2) homeostasis. RESULTS: Our results show that A.
castellanii expresses similar, to near identical types of primitive calcium
channels Cav Ac and CaM that are well known targets of loperamide in humans. The
growth assays showed anti-amoebic effects of loperamide at different doses, both
alone and in combinations with other Ca+2- CaM inhibitors. The synergistic
actions of loperamide with haloperidol showed to be more amoebicidal than when
either of them used alone. Imaging with Annexin V, Acridine orange and Propidium
iodide showed apoptosis in A. castellanii at a dose of 100 ug/ml and necrosis at
higher doses of 250 ug/ml. CONCLUSION: Though, Acanthamoeba does not express a
homolog of the human mu-opioid receptor, but does shows evidence of the homologs
for other known human targets of loperamide that are involved in Ca+2 uptake and
Ca+2 signal transduction pathways. This suggests optimization of similar drug
interactions with these targets may be useful in developing new approaches to
control the growth of this parasite and possibly the diseases caused by it.
PMID- 28506205
TI - In silico pathway analysis and tissue specific cis-eQTL for colorectal cancer
GWAS risk variants.
AB - BACKGROUND: Genome-wide association studies have identified 55 genetic variants
associated with colorectal cancer risk to date. However, potential causal genes
and pathways regulated by these risk variants remain to be characterized.
Therefore, we performed gene ontology enrichment and pathway analyses to
determine if there was an enrichment of genes in proximity to the colorectal
cancer risk variants that could further elucidate the probable causal genes and
pathways involved in colorectal cancer biology. RESULTS: For the 65 unique genes
that either contained, or were immediately neighboring up- and downstream, of
these variants there was a significant enrichment for the KEGG pathway, Pathways
in Cancer (p-value = 2.67 * 10-5) and an enrichment for multiple biological
processes (FDR < 0.05), such as cell junction organization, tissue morphogenesis,
regulation of SMAD protein phosphorylation, and odontogenesis identified through
Gene Ontology analysis. To identify potential causal genes, we conducted a cis
expression quantitative trait loci (cis-eQTL) analysis using gene expression and
genotype data from the Genotype-Tissue Expression (GTEx) Project portal in normal
sigmoid (n = 124) and transverse (n = 169) colon tissue. In addition, we also did
a cis-eQTL analysis on colorectal tumor tissue (n = 147) from The Cancer Genome
Atlas (TCGA). We identified two risk alleles that were significant cis-eQTLs for
FADS2 (rs1535) and COLCA1 and 2 (rs3802842) genes in the normal transverse colon
tissue and two risk alleles that were significant cis-eQTLs for the CABLES2
(rs2427308) and LIPG (rs7229639) genes in the normal sigmoid colon tissue, but
not tumor tissue. CONCLUSIONS: Our data reaffirm the potential to identify an
enrichment for biological processes and candidate causal genes based on
expression profiles correlated with genetic risk alleles of colorectal cancer,
however, the identification of these significant cis-eQTLs is context and tissue
specific.
PMID- 28506206
TI - Females of a gift-giving spider do not trade sex for food gifts: a consequence of
male deception?
AB - BACKGROUND: Polyandry is commonly maintained by direct benefits in gift-giving
species, so females may remate as an adaptive foraging strategy. However, the
assumption of a direct benefit fades in mating systems where male gift-giving
behaviour has evolved from offering nutritive to worthless (non-nutritive) items.
In the spider Paratrechalea ornata, 70% of gifts in nature are worthless. We
therefore predicted female receptivity to be independent of hunger in this
species. We exposed poorly-fed and well-fed females to multiple males offering
nutritive gifts and well-fed females to males offering worthless gifts. RESULTS:
Though the treatments strongly affected fecundity, females of all groups had
similar number of matings. This confirms that female receptivity is independent
of their nutritional state, i.e. polyandry does not prevail as a foraging
strategy. CONCLUSIONS: In the spider Pisaura mirabilis, in which the majority
(62%) of gifts in nature are nutritive, female receptivity depends on hunger. We
therefore propose that the dependence of female receptivity on hunger state may
have evolved in species with predominantly nutritive gifts but is absent in
species with predominantly worthless gifts.
PMID- 28506207
TI - The midgut transcriptome of Aedes aegypti fed with saline or protein meals
containing chikungunya virus reveals genes potentially involved in viral midgut
escape.
AB - BACKGROUND: The mosquito Aedes aegypti is the primary vector for medically
important arthropod-borne viruses, including chikungunya virus (CHIKV). Following
oral acquisition, an arbovirus has to persistently infect several organs in the
mosquito before becoming transmissible to another vertebrate host. A major
obstacle an arbovirus has to overcome during its infection cycle inside the
mosquito is the midgut escape barrier, representing the exit mechanism
arboviruses utilize when disseminating from the midgut. To understand the
transcriptomic basis of midgut escape and to reveal genes involved in the
process, we conducted a comparative transcriptomic analysis of midgut samples
from mosquitoes which had received a saline meal (SM) or a protein meal (PM)
(not) containing CHIKV. RESULTS: CHIKV which was orally acquired by a mosquito
along with a SM or PM productively infected the midgut epithelium and
disseminated to secondary tissues. A total of 27 RNA-Seq libraries from midguts
of mosquitoes that had received PM or SM (not) containing CHIKV at 1 and 2 days
post-feeding were generated and sequenced. Fewer than 80 genes responded
differentially to the presence of CHIKV in midguts of mosquitoes that had
acquired the virus along with SM or PM. SM feeding induced differential
expression (DE) of 479 genes at day 1 and 314 genes at day 2 when compared to
midguts of sugarfed mosquitoes. By comparison, PM feeding induced 6029 DE genes
at day 1 and 7368 genes at day 2. Twenty-three DE genes encoding trypsins,
metalloproteinases, and serine-type endopeptidases were significantly upregulated
in midguts of mosquitoes at day 1 following SM or PM ingestion. Two of these
genes were Ae. aegypti late trypsin (AeLT) and serine collagenase 1 precursor
(AeSP1). In vitro, recombinant AeLT showed strong matrix metalloproteinase
activity whereas recombinant AeSP1 did not. CONCLUSIONS: By substituting a
bloodmeal for SM, we identified midgut-expressed genes not involved in blood or
protein digestion. These included genes coding for trypsins, metalloproteinases,
and serine-type endopeptidases, which could be involved in facilitating midgut
escape for arboviruses in Ae. aegypti. The presence of CHIKV in any of the
ingested meals had relatively minor effects on the overall gene expression
profiles in midguts.
PMID- 28506208
TI - A strategy to apply quantitative epistasis analysis on developmental traits.
AB - BACKGROUND: Genetic interactions are keys to understand complex traits and
evolution. Epistasis analysis is an effective method to map genetic interactions.
Large-scale quantitative epistasis analysis has been well established for single
cells. However, there is a substantial lack of such studies in multicellular
organisms and their complex phenotypes such as development. Here we present a
method to extend quantitative epistasis analysis to developmental traits.
METHODS: In the nematode Caenorhabditis elegans, we applied RNA interference on
mutants to inactivate two genes, used an imaging system to quantitatively measure
phenotypes, and developed a set of statistical methods to extract genetic
interactions from phenotypic measurement. RESULTS: Using two different C. elegans
developmental phenotypes, body length and sex ratio, as examples, we showed that
this method could accommodate various metazoan phenotypes with performances
comparable to those methods in single cell growth studies. Comparing with
qualitative observations, this method of quantitative epistasis enabled detection
of new interactions involving subtle phenotypes. For example, several sex-ratio
genes were found to interact with brc-1 and brd-1, the orthologs of the human
breast cancer genes BRCA1 and BARD1, respectively. We confirmed the brc-1
interactions with the following genes in DNA damage response: C34F6.1, him-3
(ortholog of HORMAD1, HORMAD2), sdc-1, and set-2 (ortholog of SETD1A, SETD1B,
KMT2C, KMT2D), validating the effectiveness of our method in detecting genetic
interactions. CONCLUSIONS: We developed a reliable, high-throughput method for
quantitative epistasis analysis of developmental phenotypes.
PMID- 28506209
TI - Peptides mimicking viral proteins of porcine circovirus type 2 were profiled by
the spectrum of mouse anti-PCV2 antibodies.
AB - BACKGROUND: Porcine circovirus 2 (PCV2) is a small, non-enveloped DNA virus
causing swine lymphocyte depletion and severe impact on the swine industry. The
aim of this study was to evaluate the antigenicity and immunogenicity of specific
peptides, and seeking the potential candidate of PCV2 peptide-based vaccine. It's
initiating from peptides reacting with PCV2-infected pig sera and peptide
immunized mouse sera. RESULTS: The data showed that the sera from PCV2-infected
pigs could react with the N-terminal (C1), middle region (C2), and C-terminal
peptide (C3) of PCV2 capsid protein (CP), ORF3 protein (N1), ORF6 protein (N2)
and ORF9 protein (N3). This study demonstrated that anti-PCV2 mouse antisera
could be generated by specific synthetic peptides (C3 and N2) and recognized PCV2
viral protein. We found that the tertiary or linear form C-terminal sequence (C3)
of PCV2 capsid peptide only appeared a local distribution in the nucleus of PCV2
infected PK cells, virus-like particles of PCV2 major appeared a local
distribution in the cytoplasm, and ORF 6 protein of PCV2 were shown unusually in
cytoplasm. Furthermore, most residues of the C1 and the C3 were presented on the
surface of PCV2 CP, in the view of 3-D structure of the CP. Our data demonstrated
that PCV2-infected pigs had higher OD405 value of anti-C3 IgG on Day 1, Month 3
and Month 6 than in Month 1. These pigs had higher anti-C3 IgM level in Month 3
and Month 6 than on Day 1 (P < 0.01). CONCLUSIONS: We demonstrated that the key
peptide (C3) mimic the C-terminal of PCV2 capsid protein which were capable of
inducing antibodies. The specific antibody against the C3 were confirmed as the
serological marker in PCV2-infected pigs.
PMID- 28506210
TI - Sucrose non-ferment 1 related protein kinase 2 (SnRK2) genes could mediate the
stress responses in potato (Solanum tuberosum L.).
AB - BACKGROUND: The SnRKs (sucrose non-fermenting 1 related protein kinase) are a
gene family coding for Ser/Thr protein kinases and play important roles in
linking the tolerance and metabolic responses of plants to abiotic stresses. To
date, no genome-wide characterization of the sucrose non-ferment 1 related
protein kinase 2 (SnRK2) subfamily has been conducted in potato (Solanum
tuberosum L.). RESULTS: In this study, eight StSnRK2 genes (StSnRK2.1- StSnRK2.8)
were identified in the genome of the potato (Solanum tuberosum L.) cultivar
'Longshu 3', with similar characteristics to SnRK2 from other plant species in
gene structure, motif distribution and secondary structures. The C-terminal
regions were highly divergent among StSnRK2s, while they all carried the similar
Ser/Thr protein kinase domain. The fluorescence of GFP fused with StSnRK2.1,
StSnRK2.2, StSnRK2.6, StSnRK2.7 and StSnRK2.8 was detected in the nucleus and
cytoplasm of onion epidermal cells with StSnRK2.3 and StSnRK2.4 mainly associated
to the nucleus while StSnRK2.5 to subcellular organelles. Expression level
analysis by qRT-PCR showed that StSnRK2.1, 2.2, 2.5 and 2.6 were more than 1 fold
higher in the root than in the leaf, tuber and stem tissues. The expressions of
StSnRK2.3, 2.7, and 2.8 were at least 1.5 folds higher in the leaf and stem than
in the root, but lower in the tuber. The expression of StSnRK2.4 was also
significantly (P < 0.05) higher in leaf, stem, and tuber than in the root. From
the perspective of the relative expressions of StSnRK2 genes in potato, ABA
treatment had a different effect from NaCl and PEG treatments. CONCLUSION: In the
present study, we identified and characterized eight SnRK2s in the potato genome.
The eight StSnRK2s exhibit similar gene structure and secondary structures in
potato to the SnRK2s found in other plant species. The relative expression of
eight genes varied among various tissues (roots, leaves, tubers, and stems) and
abiotic stresses (ABA, NaCl and PEG-6000) with the prolongation of treatments.
This study provides valuable information for the future functional dissection of
potato SnRK2 genes in stress signal transduction, plant growth and development.
PMID- 28506211
TI - Interstitial pneumonia pattern on day 7 chest radiograph predicts
bronchopulmonary dysplasia in preterm infants.
AB - BACKGROUND: Early identification of infants at higher risk of developing
bronchopulmonary dysplasia (BPD) may enable a targeted approach to reduce BPD. We
aimed to evaluate the hypothesis that the interstitial pneumonia pattern on the
day 7 chest radiograph predicts BPD or death before 36 weeks postmenstrual age
(PMA). METHODS: A retrospective cohort study was performed on 336 preterm infants
(birth weight < 1500 g and gestational age < 32 postmenstrual weeks) who were
admitted to a single tertiary academic center between January 2008 and December
2014. Day 7 chest radiographs were independently reviewed by two pediatric
radiologists who were unaware of the clinical information regarding each
individual infant. RESULTS: Data from 304 infants who survived more than 7 days
after birth were collected. The interstitial pneumonia pattern on the day 7 chest
radiograph was independently associated with BPD or death before 36 weeks PMA
(odds ratio [OR] 4.0, 95% confidence interval [CI] 1.1-14.4). The interstitial
pneumonia pattern on the day 7 chest radiograph predicted BPD or death with a
specificity of 98%. Histologic chorioamnionitis was a preceding factor that was
independently associated with the interstitial pneumonia pattern on the day 7
chest radiograph (OR 3.7, 95% CI 1.3-10.3). CONCLUSIONS: The interstitial
pneumonia pattern on the day 7 chest radiograph has a high specificity for
predicting BPD or death and can be utilized to select high-risk preterm infants
who will benefit from potentially preventive interventions against BPD.
PMID- 28506212
TI - GUIDEseq: a bioconductor package to analyze GUIDE-Seq datasets for CRISPR-Cas
nucleases.
AB - BACKGROUND: Genome editing technologies developed around the CRISPR-Cas9 nuclease
system have facilitated the investigation of a broad range of biological
questions. These nucleases also hold tremendous promise for treating a variety of
genetic disorders. In the context of their therapeutic application, it is
important to identify the spectrum of genomic sequences that are cleaved by a
candidate nuclease when programmed with a particular guide RNA, as well as the
cleavage efficiency of these sites. Powerful new experimental approaches, such as
GUIDE-seq, facilitate the sensitive, unbiased genome-wide detection of nuclease
cleavage sites within the genome. Flexible bioinformatics analysis tools for
processing GUIDE-seq data are needed. RESULTS: Here, we describe an open source,
open development software suite, GUIDEseq, for GUIDE-seq data analysis and
annotation as a Bioconductor package in R. The GUIDEseq package provides a
flexible platform with more than 60 adjustable parameters for the analysis of
datasets associated with custom nuclease applications. These parameters allow
data analysis to be tailored to different nuclease platforms with different
length and complexity in their guide and PAM recognition sequences or their DNA
cleavage position. They also enable users to customize sequence aggregation
criteria, and vary peak calling thresholds that can influence the number of
potential off-target sites recovered. GUIDEseq also annotates potential off
target sites that overlap with genes based on genome annotation information, as
these may be the most important off-target sites for further characterization. In
addition, GUIDEseq enables the comparison and visualization of off-target site
overlap between different datasets for a rapid comparison of different nuclease
configurations or experimental conditions. For each identified off-target, the
GUIDEseq package outputs mapped GUIDE-Seq read count as well as cleavage score
from a user specified off-target cleavage score prediction algorithm permitting
the identification of genomic sequences with unexpected cleavage activity.
CONCLUSION: The GUIDEseq package enables analysis of GUIDE-data from various
nuclease platforms for any species with a defined genomic sequence. This software
package has been used successfully to analyze several GUIDE-seq datasets. The
software, source code and documentation are freely available at
http://www.bioconductor.org/packages/release/bioc/html/GUIDEseq.html .
PMID- 28506214
TI - Origins location of the outflow tract ventricular arrhythmias exhibiting qrS
pattern or QS pattern with a notch on the descending limb in lead V1.
AB - BACKGROUND: Ventricular outflow tract(VOT) ventricular arrhythmias(VAs)
presenting qrS pattern or QS pattern with a notch on the descending limb in lead
V1 were consistently thought of arising from the commissure between left and
right coronary cusp (L-RCC) by previous studies. However, we found they could
originate from other anatomic structures in VOT. This study aimed to investigate
the exact origin of this kind VAs. METHODS: Forty-nine patients of VOT premature
ventricular contrations/ventricular tachycardia(PVCs/VT) with lead V1 presenting
qrS pattern or QS pattern with a notch on the descending limb undergoing
successful radiofrequency catheter ablation(RFCA) in our center were analyzed.
RESULTS: 12-lead electrocardiogram(ECG) of these PVCs/VT were summarized. Among
these PVCs/VT, 37 cases exhibited qrS morphology in lead V1, 12 cases presented
QS pattern with a notch on the descending limb in the same lead. Based on the
successful ablation sites, these PVCs/VT were divided into 2 groups: (1)Right
ventricular outflow tract(RVOT) group (26 cases), and (2) Left ventricular
outflow tract (LVOT) group(23 cases, 4 cases originating from the left coronary
cusp(LCC), 2 from the right coronary cusp(RCC), 16 from the L-RCC, 1 from the
area inferior to LCC(ILCC)). The ECG characteristics of each PVCs/VT were
analyzed. Among these PVCs/VT, applying the precordial transitional zone index(TZ
index) < 0 to predict LVOT origin was demonstrated with sensitivity of 95.65%,
specificity of 96.15%, positive predicting value(PPV) of 95.65% and negative
predicting value(NPV) of 96.15%. In LVOT group, further applying the r, R, m,or
Rs morphology in lead I to predict L-RCC and RCC origin was demonstrated with
sensitivity of 94.44%, specificity of 60.00%, PPV of 89.47% and NPV of 75.00%.
CONCLUSIONS: Ventricular outflow tract PVCs/VT with lead V1 presenting qrS
pattern or QS pattern with a notch on descending limb not only arising from L
RCC, but also RVOT, LCC, RCC and ILCC. Combining TZ index and QRS morphology in
lead I to predict origin site of these kind VAs is a convenient, simple and
reliable method and facilitates the RFCA procedure.
PMID- 28506213
TI - Voxel-wise correlations between cognition and cerebral blood flow using arterial
spin-labeled perfusion MRI in patients with Alzheimer's disease: a cross
sectional study.
AB - BACKGROUND: To analyze voxel-wise correlation between cerebral blood flow (CBF)
measured using ASL-MRI and cognition in patients with Alzheimer's disease (AD).
METHODS: Forty-one patients diagnosed with AD or mild cognitive impairment due to
AD were recruited for this study. CBF images were obtained using ASL-MRI (n = 41)
with a post-labeling delay (PLD) of 1.5 and 2.5 s (PLD1.5 and PLD2.5,
respectively) using a 3 T scanner, in addition to brain perfusion SPECT with N
isopropyl-4-[I-123]iodoamphetamine (n = 28). Voxel-based analyses were performed
for ASL-MRI and SPECT using Mini-Mental State Examination (MMSE) scores as
covariates. Differences in CBF between PLD1.5 and PLD2.5 were assessed using a
paired t-test with SPM12. RESULTS: Significant positive correlations were
observed between MMSE scores and CBF at PLD1.5 in the right posterior cingulate
cortex (PCC), and both temporo-parietal association cortexes. At PLD2.5,
significant positive correlations were determined for MMSE scores and CBF in the
superior parietal lobule and the right temporo-parietal association cortex. SPECT
showed significant positive correlations in the PCC and both temporo-parietal
association cortexes (right-side dominant). PLD1.5 showed significantly higher
CBF than PLD2.5 in the proximal areas of vascular territories of the anterior,
middle, and posterior cerebral arteries. CONCLUSIONS: Significant positive
correlations in CBF, measured with both ASL-MRI and SPECT, with cognition were
found in the PCC and temporo-parietal association cortexes. PLD1.5 and PLD2.5
showed similar correlations with cognition, although the CBF images had
significant differences.
PMID- 28506215
TI - Comparison of antibody responses against Mycobacterium tuberculosis antigen
Rv0679c in tuberculosis patients from the endemic and non-endemic regions of the
Beijing genotype: a case control study.
AB - BACKGROUND: Strains of the Beijing genotype of Mycobacterium tuberculosis (MTB)
are reportedly associated with the virulence of tuberculosis (TB) infection,
unfavorable outcomes of anti-TB treatment, and the global TB pandemic. Rv0679c, a
hypothetical membrane protein related to host cell invasion, has a Beijing
genotype-specific mutation at residue 142 (Asn142Lys). Antigenicity differences
between Rv0679c-Asn142 (N-type) and Rv0679c-Lys142 (K-type) have been previously
observed in mice antigen-antibody responses. However, the immune response to
Rv0679c in humans remains unknown. Therefore, we aimed to investigate the anti
Rv0679c immune response in TB patients from the endemic and non-endemic regions
of the Beijing MTB genotype. METHODS: We analyzed the Rv0679c-specific antibody
responses in 84 subjects from the endemic region of the Beijing genotype MTB in
China, including 45 pulmonary TB patients (C-PTB) and 39 healthy controls (C-HC),
and 81 subjects from the Philippines (the endemic region of the non-Beijing
genotype), including 51 pulmonary TB patients (P-PTB) and 30 healthy controls (P
HC). Anti-tuberculous-glycolipid (TBGL) antigen was used as the control antibody.
RESULTS: TBGL IgG titers were higher in both C-PTB and P-PTB than those in their
corresponding HC (C-PTB median 4.2, P-PTB median 11.2; C-PTB vs. P-PTB, p >
0.05), suggesting immune response comparability in PTB from two different
countries. C-PTB showed a higher response compared to C-HC for anti-K-type IgG
(53.3%) than anti-N-type IgG (6.67%); this response was not observed in P-PTB
(both N-type and K-type 9.80%). CONCLUSION: Dimorphic antigen Rv0679c was found
to be associated with distinct immune response patterns, indicating the role of
Beijing/non-Beijing genotype of MTB in stimulating specific responses in TB
patients from the endemic region of Beijing MTB. Meanwhile, reactions to Rv0679c
in patients and HC from non-endemic regions of the Beijing MTB may be caused by
the response to the common epitope of Rv0679c N/K-type.
PMID- 28506216
TI - Nutritional determinants of frailty in older adults: A systematic review.
AB - BACKGROUND: Frailty is a geriatric syndrome that affects multiple domains of
human functioning. A variety of problems contributes to the development of this
syndrome; poor nutritional status is an important determinant of this condition.
The purpose of this systematic review was to examine recent evidence regarding
the association between nutritional status and frailty syndrome in older adults.
METHODS: PubMed, Web of Science, and Scopus electronic databases were searched
using specific key words, for observational papers that were published during the
period from 2005 to February 2017 and that studied the association or
relationship between nutritional status and frailty in older adults. The
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
Statement was followed to assess the quality of the included articles. RESULTS:
Of the 2042 studies found, nineteen met the inclusion criteria. Of these studies,
five provided data on micronutrients and frailty, and reported that frailty
syndrome is associated with low intakes of specific micronutrients. Five studies
provided data on macronutrients and frailty, and among those studies, four
revealed that a higher protein intake was associated with a lower risk of
frailty. Three studies examined the relationship between diet quality and
frailty, and showed that the quality of the diet is inversely associated with the
risk of being frail. Two studies provided data on the antioxidant capacity of the
diet and frailty, and reported that a high dietary antioxidant capacity is
associated with a lower risk of developing frailty. Finally, seven studies
evaluated the relationship between scores on both the Mini Nutritional Assessment
(MNA) and the MNA-SF (Short Form) and frailty, and revealed an association
between malnutrition and/or the risk of malnutrition and frailty. CONCLUSIONS:
This systematic review confirms the importance of both quantitative (energy
intake) and qualitative (nutrient quality) factors of nutrition in the
development of frailty syndrome in older adults. However, more longitudinal
studies on this topic are required to further understand the potential role of
nutrition in the prevention, postponement, or even reversion of frailty syndrome.
PMID- 28506217
TI - Association between maternal social deprivation and prenatal care utilization:
the PreCARE cohort study.
AB - BACKGROUND: Maternal social deprivation is associated with an increased risk of
adverse maternal and perinatal outcomes. Inadequate prenatal care utilization
(PCU) is likely to be an important intermediate factor. The health care system in
France provides essential health services to all pregnant women irrespective of
their socioeconomic status. Our aim was to assess the association between
maternal social deprivation and PCU. METHODS: The analysis was performed in the
database of the multicenter prospective PreCARE cohort study. The population
source consisted in all parturient women registered for delivery in 4 university
hospital maternity units, Paris, France, from October 2010 to November 2011 (N =
10,419). This analysis selected women with singleton pregnancies that ended after
22 weeks of gestation (N = 9770). The associations between maternal deprivation
(four variables first considered separately and then combined as a social
deprivation index: social isolation, poor or insecure housing conditions, no work
related household income, and absence of standard health insurance) and
inadequate PCU were tested through multivariate logistic regressions also
adjusted for immigration characteristics and education level. RESULTS: Attendance
at prenatal care was poor for 23.3% of the study population. Crude relative risks
and confidence intervals for inadequate PCU were 1.6 [1.5-1.8], 2.3 [2.1-2.6],
and 3.1 [2.8-3.4], for women with a deprivation index of 1, 2, and 3,
respectively, compared to women with deprivation index of 0. Each of the four
deprivation variables was significantly associated with an increased risk of
inadequate PCU. Because of the interaction observed between inadequate PCU and
mother's country of birth, we stratified for the latter before the multivariate
analysis. After adjustment for the potential confounders, this social gradient
remained for women born in France and North Africa. The prevalence of inadequate
PCU among women born in sub-Saharan Africa was 34.7%; the social gradient in this
group was attenuated and no longer significant. Other factors independently
associated with inadequate PCU were maternal age, recent immigration, and
unplanned or unwanted pregnancy. CONCLUSION: Social deprivation is independently
associated with an increased risk of inadequate PCU. Recognition of risk factors
is an important step in identifying barriers to PCU and developing measures to
overcome them.
PMID- 28506218
TI - Investigation of the pathophysiology of cardiopulmonary bypass using rodent
extracorporeal life support model.
AB - BACKGROUND: Extracorporeal life support (ECLS) systems are life-saving devices
used for treating patients with severe cardiopulmonary failure. In this study, we
implemented a rat model of ECLS without the administration of inotropes or
vasopressors. METHODS: The rats underwent 5 min of untreated asphyxial cardiac
arrest and were resuscitated by ECLS for 30 min. The right external jugular vein
and right femoral artery were separately cannulated to the ECLS outflow and
inflow, respectively. Thereafter, ECLS was terminated, wounds were closed, and
mechanical ventilation was provided for another 90 min. Subsequently, blood gas
and hemodynamic analyses were performed. The plasma levels of C-reactive protein
(CRP), interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-alpha)
were measured 120 min after reperfusion. RESULTS: The metabolic rate of lactate
in the group of asphyxial cardiac arrest rescued by ECLS was slow; therefore, the
pH at 120 min after reperfusion was significantly lower in this group than that
in the group of normal rats treated with ECLS. The hemodynamic data showed no
between-group differences. The plasma levels of CRP, IL-6, IL-10, and TNF-alpha
increased after ECLS treatment. CONCLUSIONS: We successfully established a rodent
ECLS model, which might be a useful approach for studying the pathophysiology
induced by ECLS under clinical conditions.
PMID- 28506219
TI - Sexual orientation differences in treatment expectation, alliance, and outcome
among patients at risk for suicide in a public psychiatric hospital.
AB - BACKGROUND: Sexual minority (SM) individuals (gay, lesbian, bisexual, or
otherwise nonheterosexual) are at increased risk for mental disorders and suicide
and adequate mental healthcare may be life-saving. However, SM patients
experience barriers in mental healthcare that have been attributed to the lack of
SM-specific competencies and heterosexist attitudes and behaviors on the part of
mental health professionals. Such barriers could have a negative impact on common
treatment factors such as treatment expectancy or therapeutic alliance,
culminating in poorer treatment outcomes for SM versus heterosexual patients.
Actual empirical data from general psychiatric settings is lacking, however.
Thus, comparing the treatment outcome of heterosexual and SM patients at risk for
suicide was the primary aim of this study. The secondary aim was to compare
treatment expectation and working alliance as two common factors. METHODS: We
report on 633 patients from a suicide prevention inpatient department within a
public psychiatric hospital. Most patients were at risk for suicide due to a
recent suicide attempt or warning signs for suicide, usually in the context of a
severe psychiatric disorder. At least one indicator of SM status was reported by
21% of patients. We assessed the treatment outcome by calculating the
quantitative change in suicide ideation, hopelessness, and depression. We also
ran related treatment responder analyses. Treatment expectation and working
alliance were the assessed common factors. RESULTS: Contrary to the primary
hypothesis, SM and heterosexual patients were comparable in their improvement in
suicide ideation, hopelessness, or depression, both quantitatively and in
treatment responder analysis. Contrary to the secondary hypothesis, there were no
significant sexual orientation differences in treatment expectation and working
alliance. When adjusting for sociodemographics, diagnosis, and length of stay,
some sexual orientation differences became significant, indicating that SM
patients have better outcomes. CONCLUSIONS: These unexpected but positive
findings may be due to common factors of therapy compensating for SM-specific
competencies. It may also be due to actual presence of SM competencies - though
unmeasured - in the department. Replication in other treatment settings and
assessment of SM-specific competencies are needed, especially in the field of
suicide prevention, before these findings can be generalized.
PMID- 28506221
TI - The association between urbanization and reduced renal function: findings from
the China Health and Nutrition Survey.
AB - BACKGROUND: While chronic kidney disease (CKD) is a growing public health concern
in low- and middle-income countries, such as China, few studies have investigated
the association between urbanization and the occurrence of CKD in those
countries. METHODS: We investigated the association between urbanization and
estimated glomerular filtration rate (eGFR), an important CKD risk marker. Data
came from the China Health and Nutrition Survey wave 2009, in which we collected
fasting serum, individual and household data along with community level
urbanization data, which was used to derive a study-specific urbanization
measure, in 218 communities across nine provinces. A total of 3644 men and 4154
women participants aged 18 years or older were included in the analysis. Reduced
renal function was defined as eGFR of less than 60 mL/min/1.73 m2 measured using
serum creatinine concentration (mg/dL). RESULTS: After adjusting for socio
demographic (e.g., age, education and household income), a sex-stratified
multilevel logistic model revealed that living in a more urbanized community was
associated with higher odds of reduced eGFR (odds ratio [OR] = 1.38 per one
standard deviation [SD] increase in the CHNS specific urbanization index, 95%
confidence interval [CI] = 1.11-1.73 for men; OR = 1.35, 95% CI = 1.11-1.62 for
women). After adjusting for behavioral variables (i.e., alcohol consumption,
smoking, physical activity and diet), as well as obesity and cardiometabolic risk
factors, the association was attenuated in men (OR = 1.25, 95% CI = 0.98-1.59),
but remained statistically significant in women (OR = 1.24, 95% CI = 1.01-1.52).
CONCLUSION: Our findings suggest that living in an urban environment is linked
with higher odds of reduced renal function independently of behavioral and
cardiometabolic risk factors, which have been shown to increase along with
urbanization.
PMID- 28506220
TI - Does the number of previous mood episodes moderate the relationship between
alcohol use, smoking and mood in bipolar outpatients?
AB - BACKGROUND: Evidence suggests that alcohol use and smoking are negatively
associated with mood in bipolar disorders (BD). It is unknown if this
relationship is moderated by the number of previous mood episodes. Therefore,
this paper aims to examine whether the number of previous mood episodes moderates
the relationship between alcohol use and smoking, and mood. METHOD: This study
assessed the outcomes of 108 outpatients with BD I and II in a prospective
observational cohort study. For 1 year, subjects daily registered mood symptoms
and substance use with the prospective Life Chart Method. The relationship
between the average daily consumption of alcohol and tobacco units in the whole
year and mood were examined by multiple linear regression analyses. Number of
previous mood episodes, grouped into its quartiles, was added as effect
moderator. Outcome was the number of depressive, hypomanic and manic days in that
year. RESULTS: The number of depressive days in a year increased by 4% (adjusted
beta per unit tobacco = 1.040; 95% CI 1.003-1.079; p = 0.033) per unit increase
in average daily tobacco consumption in that same year. Interaction analyses
showed that in those subjects with less than 7 previous mood episodes, the number
of manic and hypomanic days increased by 100.3% per unit increase in alcohol
consumption (adjusted beta per unit alcohol = 2.003; 95% CI 1.225-3.274; p =
0.006). In those with 7 to 13 previous mood episodes, the number of manic and
hypomanic days decreased by 28.7% per unit increase in alcohol consumption
(adjusted beta per unit alcohol = 0.713; 95% CI 0.539-0.944; p = 0.019); and in
subjects with 14 to 44 previous mood episodes, the number of manic and hypomanic
days decreased by 7.2% per unit increase in tobacco consumption (adjusted beta
per unit tobacco = 0.928; 95% CI 0.871-0.989; p = 0.021). CONCLUSIONS: The number
of previous mood episodes moderates the relationship between alcohol use and
smoking and mood; and smoking is adversely associated with the number of
depressive days.
PMID- 28506222
TI - Computational fluid dynamics study of intra-arterial chemotherapy for oral
cancer.
AB - BACKGROUND: Intra-arterial chemotherapy (IAC) for oral cancer can deliver a
higher concentration of anticancer agent into a tumor-feeding artery than
intravenous systemic chemotherapy. However, distribution of anticancer agent into
several branches of the external carotid artery (ECA) in IAC has not demonstrated
sufficient treatment efficacy. To improve the effectiveness of IAC, the flow
distribution of anticancer agent into the branches of the ECA in several IAC
methods was investigated using computational fluid dynamics (CFD). METHODS:
Patient-specific three-dimensional vessel models were created from CT images of 2
patients with tongue cancer. Catheter models were combined with the vessel
models. Thirty-two models were generated with varying vertical and horizontal
positions of the catheter tip. With the use of a zero-dimensional resistance
model of the peripheral vessel network, conventional IAC and superselective IAC
were simulated in 30 and 2 models, respectively. The flow distribution of
anticancer agent into the branches of the ECA was investigated in 32 models.
Additionally, the blood streamline was traced from the inlet of the common
carotid artery toward each outlet to examine the flow of anticancer agent in all
models, and the wall shear stress of the vessel was calculated for some models.
RESULTS: The CFD simulations could be conducted within a reasonable computational
time. In several models, the anticancer agent flowed into the target artery only
when the catheter tip was located below the bifurcation of the ECA and each
target artery. Furthermore, the anticancer agent tended to flow into the target
artery when the catheter tip was shifted toward the target artery. In all ECA
branches that had flow of anticancer agent, the blood streamlines to the target
arteries contacted the catheter tip. Anticancer agent flowed into only the target
artery in patients' models for superselective IAC. However, high wall shear
stress was observed at the target artery in one patient's model. CONCLUSIONS:
This CFD study showed that location of the catheter tip was important in
controlling the anticancer agent in conventional IAC. The distribution rate of
anticancer agent into the tumor-feeding artery tended to increase when the
catheter tip was placed below and toward the target artery. Although
superselective IAC can reliably supply anticancer agent to the target artery,
high wall shear stress at the target artery can occur, depending on vessel
geometry of the patient, which may cause serious complications during the
treatment.
PMID- 28506223
TI - Case of asteroid hyalosis that developed severely reduced vision after cataract
surgery.
AB - BACKGROUND: To report our findings in a patient with asteroid hyalosis (AH) who
had a severe reduction of his visual acuity following cataract surgery. The
vision was improved by vitreous surgery. CASE PRESENTATION: The patient was an 81
year-old man. Following cataract surgery on his left eye, his decimal best
corrected visual acuity (BCVA) was markedly reduced from 0.2 to 0.02. A large
number of asteroid bodies (ABs) was observed to be concentrated on the posterior
surface of the implanted intraocular lens. Ultrasound B-mode images showed
turbidity of the vitreous that was denser in the anterior vitreous where the ABs
were concentrated. During vitrectomy, the ABs were observed to be concentrated in
the anterior vitreous cavity, and a complete posterior vitreous detachment (PVD)
was present. After vitrectomy successfully removed the ABs, the visibility of the
fundus improved and the BCVA recovered to 1.0. CONCLUSION: We suggest that the
visual impairment after the cataract surgery was due to the concentrated ABs in
the anterior vitreous cavity. The clustering of the ABs in the anterior vitreous
cavity was most likely caused by the PVD that developed during the cataract
surgery.
PMID- 28506224
TI - Funding and remuneration of interdisciplinary primary care teams in Canada: a
conceptual framework and application.
AB - BACKGROUND: Reliance on interdisciplinary teams in the delivery of primary care
is on the rise. Funding bodies strive to design financial environments that
support collaboration between providers. At present, the design of financial
arrangements has been fragmented and not based on evidence. The root of the
problem is a lack of systematic evidence demonstrating the superiority of any
particular financial arrangement, or a solid understanding of options. In this
study we develop a framework for the conceptualization and analysis of financial
arrangements in interdisciplinary primary care teams. METHODS: We use qualitative
data from three sources: (i) interviews with 19 primary care decision makers
representing 215 clinics in three Canadian provinces, (ii) a research roundtable
with 14 primary care decision makers and/or researchers, and (iii) policy
documents. Transcripts from interviews and the roundtable were coded thematically
and a framework synthesis approach was applied. RESULTS: Our conceptual framework
differentiates between team level funding and provider level remuneration, and
characterizes the interplay and consonance between them. Particularly the notions
of hierarchy, segregation, and dependence of provider incomes, and the link
between funding and team activities are introduced as new clarifying concepts,
and their implications explored. The framework is applied to the analysis of
collaboration incentives, which appear strongest when provider incomes are
interdependent, funding is linked to the team as a whole, and accountability does
not have multiple lines. Emergent implementation issues discussed by respondents
include: (i) centrality of budget negotiations; (ii) approaches to patient
rostering; (iii) unclear funding sources for space and equipment; and (iv)
challenges with community engagement. The creation of patient rosters is
perceived as a surprisingly contentious issue, and the challenges of funding for
space and equipment remain unresolved. CONCLUSIONS: The development and
application of a conceptual framework is an important step to the systematic
study of the best performing financial models in the context of interdisciplinary
primary care. The identification of optimal financial arrangements must be
contextualized in terms of feasibility and the implementation environment. In
general, financial hierarchy, both overt and covert, is considered a barrier to
collaboration.
PMID- 28506225
TI - HealthRecSys: A semantic content-based recommender system to complement health
videos.
AB - BACKGROUND: The Internet, and its popularity, continues to grow at an
unprecedented pace. Watching videos online is very popular; it is estimated that
500 h of video are uploaded onto YouTube, a video-sharing service, every minute
and that, by 2019, video formats will comprise more than 80% of Internet traffic.
Health-related videos are very popular on YouTube, but their quality is always a
matter of concern. One approach to enhancing the quality of online videos is to
provide additional educational health content, such as websites, to support
health consumers. This study investigates the feasibility of building a content
based recommender system that links health consumers to reputable health
educational websites from MedlinePlus for a given health video from YouTube.
METHODS: The dataset for this study includes a collection of health-related
videos and their available metadata. Semantic technologies (such as SNOMED-CT and
Bio-ontology) were used to recommend health websites from MedlinePlus. A total of
26 healths professionals participated in evaluating 253 recommended links for a
total of 53 videos about general health, hypertension, or diabetes. The relevance
of the recommended health websites from MedlinePlus to the videos was measured
using information retrieval metrics such as the normalized discounted cumulative
gain and precision at K. RESULTS: The majority of websites recommended by our
system for health videos were relevant, based on ratings by health professionals.
The normalized discounted cumulative gain was between 46% and 90% for the
different topics. CONCLUSIONS: Our study demonstrates the feasibility of using a
semantic content-based recommender system to enrich YouTube health videos.
Evaluation with end-users, in addition to healthcare professionals, will be
required to identify the acceptance of these recommendations in a nonsimulated
information-seeking context.
PMID- 28506226
TI - Institutional delivery service utilization and associated factors among women of
reproductive age in the mobile pastoral community of the Liban District in Guji
Zone, Oromia, Southern Ethiopia: a cross sectional study.
AB - BACKGROUND: Globally, an estimated 289,000 maternal deaths occurred in 2013.
Majority of these deaths occurred in sub-Saharan Africa and Southern Asia.
Mobility of pastoralists is a well-recognized survival strategy in arid and semi
arid land of sub-Saharan Africa. However governments often encourage settlement
as a solution to the difficulty of providing health services for mobile
pastoralists. This study aimed to assess utilization of institutional delivery
and associated factors among women of reproductive age in the mobile pastoral
community of the Liban District in Guji zone, Oromia, Ethiopia. METHODS: A
Community based cross-sectional survey was conducted among the mobile pastoralist
community of the Liban District. Seven hundred ninety-one (791) randomly selected
women, who had birth within the last 2 years preceding the survey, were
interviewed using a pretested structured questionnaire. Data were entered into
Epi-Info version 3.5.4 and analyzed by Statistical Package for Social Science
(SPSS) version 16. Bivariate and multivariate analyses were done. RESULTS: Out of
791 women who gave birth within the last 2 years preceding the survey, only 110
(13.9%) gave birth in health institutions. Majority (74.1%) of the women gave
birth at their home. Ninety-one women (11.5%) gave birth at traditional birth
attendant's home; assisted by traditional birth attendants. Multiple logistic
regression shows that women who had readily available cash at the onset of labor
(aOR 2.79, 95% CI: 1.29-6.25), delivered the birth preceding the most recent
birth in a health institution (aOR 6.8, 95% CI: 3.44-13.45) and had birth related
complications during the birth preceding the most recent birth (aOR 1.90, 95% CI:
1.08-3.36) were more likely to deliver at health institutions. CONCLUSION:
Majority of the pastoral women seek institutional delivery, only when labor
related complications are perceived. Mechanisms of alleviating indirect health
care costs affecting institutional delivery need to be addressed in future
studies.
PMID- 28506227
TI - Associations between disc space narrowing, anterior osteophytes and disability in
chronic mechanical low back pain: a cross sectional study.
AB - BACKGROUND: Radiographic features of lumbar disc degeneration (LDD) are common
findings in patients with chronic mechanical low back pain; however, its role in
disability and intensity of pain is debatable. This study aims to investigate the
associations of the x-ray features of LDD and lumbar spondylolisthesis with
severity of disability and intensity of pain. METHODS: A cross-sectional study
was conducted on 439 patients with chronic mechanical low back pain who attended
the rheumatology clinic, National Hospital of Sri Lanka, Colombo, from May 2012
to May 2014. Severity of disability was measured using Modified Oswestry
Disability Index and intensity of pain was assessed using numeric rating scale (0
100). X-ray features of LDD (disc space narrowing, anterior osteophytes and
overall LDD) and spondylolisthesis were assessed in lateral recumbent lumbar x
rays (L1/L2 to L5/S1) and graded by a consultant radiologist blinded to clinical
data. Generalised linear model with linear response was used to assess the
associations of x-ray features of LDD with severity of disability and intensity
of pain adjusting for age, gender, body mass index and pain radiating into legs.
RESULTS: Mean age was 48.99 +/- 11.21 and 323 (73.58%) were females. 87 (19.82%)
were obese. Mean severity of disability was 30.95 +/- 13.67 and mean intensity of
pain was 45.50 +/- 20.37. 69 (15.72%), 26 (5.92%) and 85 (19.36%) patients had
grade 2 disc space narrowing, anterior osteophytes and overall LDD, respectively.
51 (11.62%) patients had lumbar spondylolisthesis. Grade of disc space narrowing
and overall LDD were not associated with severity of disability or intensity of
pain. The presence of lumbar spondylolisthesis was associated with severity of
disability. Female gender and pain radiating into legs were associated with
severity of disability and intensity of pain. Advancing age was associated with x
ray features of LDD and lumbar spondylolisthesis. CONCLUSIONS: Lumbar
spondylolisthesis is associated with severity of disability in patients with
chronic mechanical low back pain. Associations of x-ray features of LDD with
severity of disability and intensity of pain are inconclusive. Female gender and
pain radiating into legs are significant confounders.
PMID- 28506228
TI - Chinese herbal Pulian ointment in treating psoriasis vulgaris of blood-heat
syndrome: a multi-center, double-blind, randomized, placebo-controlled trial.
AB - BACKGROUND: Traditional Chinese medicine (TCM) has a long history in the
treatment of psoriasis vulgaris. We aimed to evaluate the clinical efficacy and
safety of Chinese herbal Pulian ointment in treating psoriasis vulgaris of blood
heat syndrome. METHODS: A multicenter, randomized, double-blind, placebo
controlled trial was conducted. Participants with psoriasis vulgaris of blood
heat syndrome were blinded and randomized to receive Pulian ointment or placebo
ointment twice daily for 4 weeks, with follow-up 8 weeks after treatment.
Psoriasis Area Severity Index (PASI) scores, severity of each symptom and area of
skin lesion and quality of life were assessed at baseline, 2 weeks, and 4 weeks.
Adverse events were recorded during the study. SAS 9.4 software and SPSS 17.0
software was applied for data analysis. RESULTS: A total of 300 participants with
psoriasis vulgaris of blood-heat syndrome were assessed for eligibility, and 294
were randomly assigned to the Pulian ointment and placebo group from six study
centers. Full analysis set (FAS): after 4 weeks of treatment, there were
significant differences between groups in PASI score and the separate score of
skin lesion area, favoring Pulian ointment group (P < 0.05). However, no
significant differences were observed in scores of scaling, erythema and
induration/thickness (P > 0.05). Per protocol set (PPS): There was no
statistically significant difference in PASI score and separate score of each
symptom and area of skin lesion between two groups (P > 0.05). Quality of life
measured by Hamilton Anxiety Rating Scale (HAMA) and 36-Item Short Form Health
Survey (SF-36) improved after treatment in both groups, but there was no
significant difference between the two groups (P > 0.05). After being followed up
for 8 weeks, the total relapse rates of the Pulian Ointment group and placebo
group were 5.88 and 8.45%, respectively, and the difference was not statistically
significant between the two groups (P > 0.05). No adverse event was observed in
both groups throughout the study. CONCLUSIONS: Pulian Ointment seems effective
and well tolerated in improving the PASI score and separate score of skin lesion
area for patients with psoriasis vulgaris of blood-heat syndrome. Further
research could build on the current study to explore whether other preparation
forms and greater intervention intensity are necessary for better therapeutic
effects. TRIAL REGISTRATION: Chictr.org.cn Identifier ChiCTR-TRC-12002054 .
PMID- 28506229
TI - Determinants of felt demand for dengue vaccines in the North Caribbean region of
Colombia.
AB - BACKGROUND: The increasing burden associated with dengue in Latin America makes
it essential to understand the community's interest in acquiring vaccines, as an
input to plan its introduction in endemic regions. The objective of this study is
to learn the felt demand for dengue vaccines by estimating the willingness to pay
and its associated factors in endemic communities of the North Caribbean region
of Colombia. METHODS: A population survey was administered from October to
December 2015, including 1037 families in 11 municipalities in Colombia. One
adult per family was interviewed on their perception and history of dengue.
Participants received a description of four hypothetical scenarios of dengue
vaccines, administered in a single dose or in 3 doses, with an effectiveness of
70% for 5 years or 95% for 30 years. The willingness to pay for each one of these
vaccines was inquired vs. 5 hypothetical prices in Colombian pesos. RESULTS: Most
participants recognized dengue as a serious disease in children (99.3%) and
adults (98.6%). 33 (3.2%) of the total respondents reported having suffered
dengue and 19 (57.6%) of them required hospitalization. The price of the vaccine
was inversely related to the willingness to pay. In addition, single dose
vaccines (compared to 3 doses) and one with a protection of 95% for 30 years
(compared to an effectiveness of 70% for 5 years), were associated with greater
willingness to pay. Greater willingness to pay was observed among the respondents
who considered it likely to get the disease, either themselves (OR 1.56; CI 95%
1.08-2.26) or their children (OR 1.89; CI 95% 1.28-2.81), in the next 5 years.
The participants who have been diagnosed with dengue also showed greater
willingness to pay (OR 1.89; CI 95% 1.01-3.54) compared to those who did not have
this history. CONCLUSION: Factors such as price, number of doses and
effectiveness can independently influence the decision to purchase a vaccine
against an endemic disease, such as dengue. Additionally, this study reveals that
background and perceptions of the disease can affect individuals' interest in
acquiring this type of preventive interventions.
PMID- 28506230
TI - Health literacy and primary health care use of ethnic minorities in the
Netherlands.
AB - BACKGROUND: In the Netherlands, ethnic minority populations visit their general
practitioner (GP) more often than the indigenous population. An explanation for
this association is lacking. Recently, health literacy is suggested as a possible
explaining mechanism. Internationally, associations between health literacy and
health care use, and between ethnicity and health literacy have been studied
separately, but, so far, have not been linked to each other. In the Netherlands,
some expectations have been expressed with regard to supposed low health literacy
of ethnic minority groups, however, no empirical study has been done so far. The
objectives of this study are therefore to acquire insight into the level of
health literacy of ethnic minorities in the Netherlands and to examine whether
the relationship between ethnicity and health care use can be (partly) explained
by health literacy. METHODS: A questionnaire was sent to a sample of 2.116
members of the Dutch Health Care Consumer Panel (response rate 46%, 89
respondents of non-western origin). Health literacy was measured with the Health
Literacy Questionnaire (HLQ) which covers nine different domains. The health
literacy levels of ethnic minority groups were compared to the indigenous
population. A negative binomial regression model was used to estimate the
association between ethnicity and GP visits. To examine whether health literacy
is an explaining factor in this association, health literacy and interaction
terms of health literacy and ethnicity were added into the model. RESULTS:
Differences in levels of health literacy were only found between the Turkish
population and the indigenous Dutch population. This study also found an
association between ethnicity and GP visits. Ethnic minorities visit their GP 33%
more often than the indigenous population. Three domains of the HLQ (the ability
to navigate the health care system, the ability to find information and to read
and understand health information) partly explained the association between
ethnicity and GP visits. CONCLUSIONS: In general, there are no differences in
health literacy between most of the ethnic minority groups in the Netherlands and
the indigenous Dutch population. Only the Turkish population scored significantly
lower on several health literacy domains. Some domains of health literacy do
explain the association between ethnicity and higher frequency of GP visits.
Further research is recommended to understand the pathways through which health
literacy impacts health care use.
PMID- 28506231
TI - Optogenetic interrogation reveals separable G-protein-dependent and -independent
signalling linking G-protein-coupled receptors to the circadian oscillator.
AB - BACKGROUND: Endogenous circadian oscillators distributed across the mammalian
body are synchronised among themselves and with external time via a variety of
signalling molecules, some of which interact with G-protein-coupled receptors
(GPCRs). GPCRs can regulate cell physiology via pathways originating with
heterotrimeric G-proteins or beta-arrestins. We applied an optogenetic approach
to determine the contribution of these two signalling modes on circadian phase.
RESULTS: We employed a photopigment (JellyOp) that activates Galphas signalling
with better selectivity and higher sensitivity than available alternatives, and a
point mutant of this pigment (F112A) biased towards beta-arrestin signalling.
When expressed in fibroblasts, both native JellyOp and the F112A arrestin-biased
mutant drove light-dependent phase resetting in the circadian clock. Shifts
induced by the two opsins differed in their circadian phase dependence and the
degree to which they were associated with clock gene induction. CONCLUSIONS: Our
data imply separable G-protein and arrestin inputs to the mammalian circadian
clock and establish a pair of optogenetic tools suitable for manipulating Galphas
and beta-arrestin-biased signalling in live cells.
PMID- 28506232
TI - Rp58 and p27kip1 coordinate cell cycle exit and neuronal migration within the
embryonic mouse cerebral cortex.
AB - BACKGROUND: During the development of the mammalian cerebral cortex, newborn
postmitotic projection neurons are born from local neural stem cells and must
undergo radial migration so as to position themselves appropriately to form
functional neural circuits. The zinc finger transcriptional repressor Rp58 (also
known as Znf238 or Zbtb18) is critical for coordinating corticogenesis, but its
underlying molecular mechanism remains to be better characterised. FINDINGS:
Here, we demonstrate that the co-expression of Rp58 and the cyclin dependent
kinase inhibitor (CDKI) p27kip1 is important for E14.5-born cortical neurons to
coordinate cell cycle exit and initiate their radial migration. Notably, we find
that the impaired radial positioning of Rp58-deficient cortical neurons within
the embryonic (E17.5) mouse cortex, as well as their multipolar to bipolar
transition from the intermediate zone to the cortical plate can be restored by
forced expression of p27kip1 in concert with suppression of Rnd2, a downstream
target gene of Rp58. Furthermore, the restorative effects of p27kip1 and Rnd2
abrogation are reminiscent of suppressing RhoA signalling in Rp58-deficient
cells. CONCLUSIONS: Our findings demonstrate functional interplay between a
transcriptional regulator and a CDKI to mediate neuroprogenitor cell cycle exit,
as well as to promote radial migration through a molecular mechanism consistent
with suppression of RhoA signalling.
PMID- 28506233
TI - Measurement and decomposition of socioeconomic inequality in single and
multimorbidity in older adults in China and Ghana: results from the WHO study on
global AGEing and adult health (SAGE).
AB - BACKGROUND: Globally people are living longer and enduring non-communicable
diseases (NCDs) many of which co-occur as multimorbidity. Demographic and
socioeconomic factors are determinants of inequalities and inequities in health.
There is a need for country-specific evidence of NCD inequalities in developing
countries where populations are ageing rapidly amid economic and social change.
The study measures and decomposes socioeconomic inequality in single and multiple
NCD morbidity in adults aged 50 and over in China and Ghana. METHODS: The data
source is the World Health Organization Study on Global AGEing and Adult Health
(SAGE) Wave 1 (2007-2010). Nationally representative cross-sectional data
collected from adults in China (n = 11,814) and Ghana (n = 4,050) are analysed.
Country populations are ranked by a socioeconomic index based on ownership of
household assets. The study uses a decomposed concentration index (CI) of single
and multiple NCD morbidity (multimorbidity) covering arthritis, diabetes, angina,
stroke, asthma, depression, chronic lung disease and hypertension. The CI
quantifies the extent of overall inequality on each morbidity measure. The
decomposition utilises a regression-based approach to examine individual
contributions of demographic and socioeconomic factors, or determinants, to the
overall inequality. RESULTS: In China, the prevalence of single and multiple NCD
morbidity was 64.7% and 53.4%, compared with 65.9% and 55.5% respectively in
Ghana. Inequalities were significant and more highly concentrated among the poor
in China (single morbidity CI = -0.0365: 95% CI = -0.0689,-0.0040; multimorbidity
CI = -0.0801: 95% CI = -0.1233,-0.0368;). In Ghana inequalities were significant
and more highly concentrated among the rich (single morbidity CI = 0.1182; 95% CI
= 0.0697, 0.1668; multimorbidity CI = 0.1453: 95% CI = 0.0794, 0.2083). In China,
rural residence contributed most to inequality in single morbidity (36.4%) and
the wealth quintiles contributed most to inequality in multimorbidity (39.0%). In
Ghana, the wealth quintiles contributed 24.5% to inequality in single morbidity
and body mass index contributed 16.2% to the inequality in multimorbidity.
CONCLUSIONS: The country comparison reflects different stages of economic
development and social change in China and Ghana. More studies of this type are
needed to inform policy-makers about the patterning of socioeconomic inequalities
in health, particularly in developing countries undergoing rapid epidemiological
and demographic transitions.
PMID- 28506235
TI - Single-staged uniportal VATS in the supine position for simultaneous bilateral
primary spontaneous pneumothorax.
AB - BACKGROUND: Simultaneous bilateral primary spontaneous pneumothorax (SBPSP) is
rare, but requires surgery on both sides, in patients with definite bilateral
bullae to prevent life-threatening conditions. Recently, uniportal video-assisted
thoracoscopic surgery (VATS) has been widely accepted as a less invasive
technique for the treatment of pneumothorax. Thus, we introduced single-staged
uniportal VATS technique in the supine position, for the management of two cases
of SBPSP. CASE PRESENTATION: A 17-year-old boy presented with bilateral
spontaneous pneumothorax and he underwent single-staged uniportal VATS in the
supine position. Single wide draping in consecutive bilateral approaches removes
the needs of changing patients' position. Whole thoracoscopic procedure for wedge
resection of bullae lesions was conducted without difficulty. The total operation
time took 65 min and the patient discharged 3 days after the operation. The
patient was followed for 24 months without recurrence of both sides. Another 18
year-old boy was admitted with bilateral spontaneous pneumothorax and single
staged uniportal VATS was also performed in the supine position. The total
operation time took 79 min and the patient discharged on postoperative day 4. He
was followed for 19 months without recurrence of both sides. CONCLUSIONS: Single
staged uniportal VATS approach yielded satisfactory results from simplicity that
not requires position change compared to conventional multi-ports VATS in the
lateral position, and with better cosmetics. This technique is thought to be a
feasible procedure in selective patients with SBPSP or with contralateral bullae
for preventive role.
PMID- 28506236
TI - Knowing where the nose is.
AB - Improvements in imaging technology and the development of powerful machine
learning algorithms are revolutionizing the study of animal behavior in the
laboratory. These innovations promise to reveal both global and local features of
action relevant to understanding how the brain functions. A study in BMC Biology
describes one such tool called OptiMouse, which is an open source platform that
uses video to capture key features of mouse behavior, including information
relevant to olfactory investigation.See research article: 10.1186/s12915-017-0377
3.
PMID- 28506234
TI - Anti-malarial medicine quality field studies and surveys: a systematic review of
screening technologies used and reporting of findings.
AB - BACKGROUND: Assessing the quality of medicines in low-middle income countries
(LMICs) relies primarily on human inspection and screening technologies, where
available. Field studies and surveys have frequently utilized screening tests to
analyse medicines sampled at the point of care, such as health care facilities
and medicine outlets, to provide a snap shot of medicine quality in a specific
geographical area. This review presents an overview of the screening tests
typically employed in surveys to assess anti-malarial medicine quality,
summarizes the analytical methods used, how findings have been reported and
proposes a reporting template for future studies. METHODS: A systematic search of
the peer-reviewed and grey literature available in the public domain (including
national and multi-national medicine quality surveys) covering the period 1990
2016 was undertaken. Studies were included if they had used screening techniques
to assess the quality of anti-malarial medicines. As no standardized set of
guidelines for the methodology and reporting of medicine quality surveys exist,
the included studies were assessed for their standard against a newly proposed
list of criteria. RESULTS: The titles and abstracts of 4621 records were screened
and only 39 were found to meet the eligibility criteria. These 39 studies
utilized visual inspection, disintegration, colorimetry and Thin Layer
Chromatography (TLC) either as components of the Global Pharma Health Fund (GPHF)
MiniLab(r) or as individual tests. Overall, 30/39 studies reported employing
confirmatory testing described in international pharmacopeia to verify the
quality of anti-malarials post assessment by a screening test. The authors
assigned scores for the 23 criteria for the standard of reporting of each study.
CONCLUSIONS: There is considerable heterogeneity in study design and
inconsistency in reporting of field surveys of medicine quality. A lack of
standardization in the design and reporting of studies of medicine quality
increases the risk of bias and error, impacting on the generalizability and
reliability of study results. The criteria proposed for reporting on the standard
of studies in this review can be used in conjunction with existing medicine
quality survey guidelines as a checklist for designing and reporting findings of
studies. The review protocol has been registered with PROSPERO (CRD42015026782).
PMID- 28506237
TI - Clinical and MRI outcome of cervical spine lesions in children with juvenile
idiopathic arthritis treated with anti-TNFalpha drugs early in disease course.
AB - BACKGROUNDS: The purpose of the study was to evaluate the clinical and magnetic
resonance imaging (MRI) outcome of cervical spine arthritis in children with
juvenile idiopathic arthritis (JIA), who received anti-TNFalpha early in the
course of cervical spine arthritis. METHODS: Medical charts and imaging of JIA
patients with cervical spine involvement were reviewed in this retrospective
study. Data, including age at disease onset, JIA type, disease activity,
treatment and clinical outcome were collected. Initial and followup MRI
examinations of cervical spine were performed according to the hospital protocol
to evaluate the presence of inflammation and potential chronic/late changes.
RESULTS: Fifteen JIA patients with MRI proved cervical spine inflammation (11
girls, 4 boys, median age 6.3y) were included in the study: 9 had polyarthritis,
3 extended oligoarthritis, 2 persistent oligoarthritis and 1 juvenile psoriatic
arthritis. All children were initially treated with high-dose steroids and
methotrexate. In addition, 11 patients were treated with anti-TNFalpha drug
within 3 months, and 3 patients within 7 months of cervical spine involvement
confirmed by MRI. Mean observation time was 2.9y, mean duration of anti-TNFalpha
treatment was 2.2y. Last MRI showed no active inflammation in 12/15 children,
allowing to stop biological treatment in 3 patients, and in 3/15 significant
reduction of inflammation. Mild chronic changes were found on MRI in 3 children.
CONCLUSIONS: Early treatment with anti-TNFalpha drugs resulted in significantly
reduced inflammation or complete remission of cervical spine arthritis proved by
MRI, and prevented the development of serious chronic/late changes. Repeated MRI
examinations are suggested in the follow-up of JIA patients with cervical spine
arthritis.
PMID- 28506238
TI - Ten-year survival rate after rotational acetabular osteotomy in adulthood hip
dysplasia.
AB - BACKGROUND: Rotational acetabular osteotomy (RAO) is an effective joint
preserving surgical treatment for adulthood hip dysplasia (AHD). Despite
sufficient correction of acetabular dysplasia, some patients still experience
osteoarthritis (OA) progression and require total hip arthroplasty (THA). The
purposes of the current study were to investigate the survival rate and the risk
factors for OA progression or THA requirement after RAO and to explore whether
acetabular overcorrection relates to OA progression. METHODS: Fifty-six patients
(65 hips, mean age: 36.5 +/- 11.7 years) with AHD who underwent RAO and were
followed up for >10 years (mean: 15.0 +/- 3.2 years) were enrolled in this study.
A Kaplan-Meier survival analysis was performed to assess the non-OA progression
rate and THA-free survival rate of RAO during the 10-year follow-up. To analyze
the risk factors for OA progression and THA requirement, the Cox proportional
hazards regression analysis was performed. RESULTS: No OA progression was found
in 76.7% of the patients, and THA was not required in 92.3% during the 10-year
follow-up. By multivariate regression analysis, older age at the time of surgery
was a risk factor for both OA progression (hazard ratio [HR] = 1.047, 95%
confidence interval [CI] = 1.005-1.091) and THA requirement (HR = 1.293, 95% CI =
1.041-1.606). CONCLUSION: RAO is an effective surgical procedure for symptomatic
patients with AHD that prevents OA progression and protects the hips from
undergoing THA. However, older patients have a higher risk for both OA
progression and THA requirement.
PMID- 28506239
TI - Dihydroartemisinin inhibits TCTP-dependent metastasis in gallbladder cancer.
AB - BACKGROUND: Patients with metastatic or relapsed gallbladder cancer generally
have a poor prognosis. Therefore, targeting metastasis is one arm of therapeutic
strategies to treat gallbladder cancer. METHODS: Levels of translationally
controlled tumor protein (TCTP) were measured in samples of gallbladder cancer by
immunohistochemical staining. Wound healing, migration and invasion assays were
used to investigate the motility of cells. Western blot assay was used to
investigate the levels of TCTP and other proteins. Liver metastasis models and
lung metastasis models were established to investigate the inhibitory effect of
Dihydroartemisinin on gallbladder cancer metastasis. RESULTS: TCTP is aberrantly
expressed in gallbladder cancer patients and associated with metastasis and a
poor prognosis. Depleting TCTP significantly inhibited gallbladder cancer cell
migration and invasion. We found that Dihydroartemisinin as a potent inhibitor of
TCTP inhibited TCTP-dependent cell migration and invasion by reducing cell
division control protein 42 homolog (Cdc42) activation. In addition, in mice with
xenografted tumors, treatment with Dihydroartemisinin decreased gallbladder
cancer cell metastases and improved survival. CONCLUSIONS: These findings provide
new insights into the therapeutic activity of Dihydroartemisinin as a treatment
for gallbladder cancer metastasis.
PMID- 28506240
TI - Inhibitors compounds of the flavivirus replication process.
AB - Flaviviruses are small viruses with single-stranded RNA, which include the yellow
fever virus, dengue virus, West Nile virus, Japanese encephalitis virus, tick
borne encephalitis virus, and Zika virus; and are causal agents of the most
important emerging diseases that have no available treatment to date. In recent
years, the strategy has focused on the development of replication inhibitors of
these viruses designed to act mainly by affecting the activity of enzyme
proteins, such as NS3 and NS5, which perform important functions in the viral
replication process. This article describes the importance of flaviviruses and
the development of molecules used as inhibitors of viral replication in this
genus.
PMID- 28506241
TI - Socio-demographic determinants of Toxoplasma gondii seroprevalence in migrant
workers of Peninsular Malaysia.
AB - BACKGROUND: The number of migrants working in Malaysia has increased sharply
since the 1970's and there is concern that infectious diseases endemic in other
(e.g. neighbouring) countries may be inadvertently imported. Compulsory medical
screening prior to entering the workforce does not include parasitic infections
such as toxoplasmosis. Therefore, this study aimed to evaluate the seroprevalence
of T. gondii infection among migrant workers in Peninsular Malaysia by means of
serosurveys conducted on a voluntary basis among low-skilled and semi-skilled
workers from five working sectors, namely, manufacturing, food service,
agriculture and plantation, construction and domestic work. METHODS: A total of
484 migrant workers originating from rural locations in neighbouring countries,
namely, Indonesia (n = 247, 51.0%), Nepal (n = 99, 20.5%), Bangladesh (n = 72,
14.9%), India (n = 52, 10.7%) and Myanmar (n = 14, 2.9%) were included in this
study. RESULTS: The overall seroprevalence of T. gondii was 57.4% (n = 278; 95%
CI: 52.7-61.8%) with 52.9% (n = 256; 95% CI: 48.4-57.2%) seropositive for anti
Toxoplasma IgG only, 0.8% (n = 4; 95% CI: 0.2-1.7%) seropositive for anti
Toxoplasma IgM only and 3.7% (n = 18; 95% CI: 2.1-5.4%) seropositive with both
IgG and IgM antibodies. All positive samples with both IgG and IgM antibodies
showed high avidity (> 40%), suggesting latent infection. Age (being older than
45 years), Nepalese nationality, manufacturing occupation, and being a newcomer
in Malaysia (excepting domestic work) were positively and statistically
significantly associated with seroprevalence (P < 0.05). CONCLUSIONS: The results
of this study suggest that better promotion of knowledge about parasite
transmission is required for both migrant workers and permanent residents in
Malaysia. Efforts should be made to encourage improved personal hygiene before
consumption of food and fluids, thorough cooking of meat and better disposal of
feline excreta from domestic pets.
PMID- 28506243
TI - Cost analysis of the very elderly admitted to intensive care units.
AB - BACKGROUND: Very elderly patients are often admitted to intensive care units
(ICUs) despite poor outcomes and frequent preference to avoid unnecessary
prolongation of life. We sought to determine the cost of ICU admission for the
very elderly and the factors influencing this cost. METHODS: This prospective,
observational cohort study included patients >=80 years old admitted to 22
Canadian ICUs from 2009 to 2013. A subset of consenting individuals comprised a
longitudinal cohort followed over 12 months. Costs were calculated from ICU
length of stay and unit costs for ICU admission from a Canadian academic
hospital. A generalized linear model was employed to identify cost-predictive
variables. RESULTS: In total, 1671 patients were included; 610 were enrolled in
the longitudinal cohort. The average age was 85 years; median ICU length of stay
was 4 days. Mortality was 35% (585/1671) in hospital and 41% (253/610) at 12
months. The average cost of ICU admission per patient was $31,679 +/- 65,867.
Estimated ICU costs were $48,744 per survivor to discharge and $61,783 per
survivor at 1 year. For both decedents and survivors, preference for comfort
measures over life support was an independent predictor for lower cost (P <
0.01). CONCLUSIONS: Considering the poor clinical outcomes, and that many ICU
admissions may be undesired by very elderly patients, ICU costs in this
population are substantial. Our finding that a preference for comfort care
predicted a lower cost independent of mortality reinforces the importance of
early goals of care discussions to avoid both undesired and potentially non
beneficial interventions, consequently reducing costs. TRIAL REGISTRATION:
ClinicalTrials.gov, NCT01293708 . Registered on 10 February 2011.
PMID- 28506242
TI - An imprinted non-coding genomic cluster at 14q32 defines clinically relevant
molecular subtypes in osteosarcoma across multiple independent datasets.
AB - BACKGROUND: A microRNA (miRNA) collection on the imprinted 14q32 MEG3 region has
been associated with outcome in osteosarcoma. We assessed the clinical utility of
this miRNA set and their association with methylation status. METHODS: We
integrated coding and non-coding RNA data from three independent annotated
clinical osteosarcoma cohorts (n = 65, n = 27, and n = 25) and miRNA and
methylation data from one in vitro (19 cell lines) and one clinical (NCI
Therapeutically Applicable Research to Generate Effective Treatments (TARGET)
osteosarcoma dataset, n = 80) dataset. We used time-dependent receiver operating
characteristic (tdROC) analysis to evaluate the clinical value of candidate miRNA
profiles and machine learning approaches to compare the coding and non-coding
transcriptional programs of high- and low-risk osteosarcoma tumors and high-
versus low-aggressiveness cell lines. In the cell line and TARGET datasets, we
also studied the methylation patterns of the MEG3 imprinting control region on
14q32 and their association with miRNA expression and tumor aggressiveness.
RESULTS: In the tdROC analysis, miRNA sets on 14q32 showed strong discriminatory
power for recurrence and survival in the three clinical datasets. High- or low
risk tumor classification was robust to using different microRNA sets or
classification methods. Machine learning approaches showed that genome-wide miRNA
profiles and miRNA regulatory networks were quite different between the two
outcome groups and mRNA profiles categorized the samples in a manner concordant
with the miRNAs, suggesting potential molecular subtypes. Further, miRNA
expression patterns were reproducible in comparing high-aggressiveness versus low
aggressiveness cell lines. Methylation patterns in the MEG3 differentially
methylated region (DMR) also distinguished high-aggressiveness from low
aggressiveness cell lines and were associated with expression of several 14q32
miRNAs in both the cell lines and the large TARGET clinical dataset. Within the
limits of available CpG array coverage, we observed a potential methylation
sensitive regulation of the non-coding RNA cluster by CTCF, a known enhancer
blocking factor. CONCLUSIONS: Loss of imprinting/methylation changes in the 14q32
non-coding region defines reproducible previously unrecognized osteosarcoma
subtypes with distinct transcriptional programs and biologic and clinical
behavior. Future studies will define the precise relationship between 14q32
imprinting, non-coding RNA expression, genomic enhancer binding, and tumor
aggressiveness, with possible therapeutic implications for both early- and
advanced-stage patients.
PMID- 28506244
TI - Early EEG for outcome prediction of postanoxic coma: prospective cohort study
with cost-minimization analysis.
AB - BACKGROUND: We recently showed that electroencephalography (EEG) patterns within
the first 24 hours robustly contribute to multimodal prediction of poor or good
neurological outcome of comatose patients after cardiac arrest. Here, we confirm
these results and present a cost-minimization analysis. Early prognosis
contributes to communication between doctors and family, and may prevent
inappropriate treatment. METHODS: A prospective cohort study including 430
subsequent comatose patients after cardiac arrest was conducted at intensive care
units of two teaching hospitals. Continuous EEG was started within 12 hours after
cardiac arrest and continued up to 3 days. EEG patterns were visually classified
as unfavorable (isoelectric, low-voltage, or burst suppression with identical
bursts) or favorable (continuous patterns) at 12 and 24 hours after cardiac
arrest. Outcome at 6 months was classified as good (cerebral performance category
(CPC) 1 or 2) or poor (CPC 3, 4, or 5). Predictive values of EEG measures and
cost-consequences from a hospital perspective were investigated, assuming EEG
based decision- making about withdrawal of life-sustaining treatment in the case
of a poor predicted outcome. RESULTS: Poor outcome occurred in 197 patients (51%
of those included in the analyses). Unfavorable EEG patterns at 24 hours
predicted a poor outcome with specificity of 100% (95% CI 98-100%) and
sensitivity of 29% (95% CI 22-36%). Favorable patterns at 12 hours predicted good
outcome with specificity of 88% (95% CI 81-93%) and sensitivity of 51% (95% CI 42
60%). Treatment withdrawal based on an unfavorable EEG pattern at 24 hours
resulted in a reduced mean ICU length of stay without increased mortality in the
long term. This gave small cost reductions, depending on the timing of
withdrawal. CONCLUSIONS: Early EEG contributes to reliable prediction of good or
poor outcome of postanoxic coma and may lead to reduced length of ICU stay. In
turn, this may bring small cost reductions.
PMID- 28506245
TI - Comparison of T24H-his, GST-T24H and GST-Ts8B2 recombinant antigens in western
blot, ELISA and multiplex bead-based assay for diagnosis of neurocysticercosis.
AB - BACKGROUND: Currently, the reference standard assay for the serodiagnosis of
neurocysticercosis (NCC) is the lentil lectin-bound glycoproteins/enzyme-linked
immunoelectrotransfer blot (LLGP-EITB). The main disadvantage of this technique
is the complexity of obtaining and purifying the LLGP extract. This could be
solved by replacement with highly specific recombinant antigens from Taenia
solium. Based on previous studies, we selected and produced the recombinant Ts8B2
and T24H proteins and applied them to three diagnostic techniques: western blot
(WB), enzyme-linked immunosorbent assay (ELISA) and the multiplex bead-based
assay (MBA). METHODS: The Ts8B2 and T24H cDNA sequences were expressed in a
prokaryotic system and the corresponding expression products purified; three
recombinant proteins were further characterized: T24H-his, GST-T24H and GST
Ts8B2. The proteins on WB, ELISA and MBA were tested against 149 sera from
patients with NCC confirmed by brain imaging, 40 sera from patients with other
parasitic diseases, and 131 sera from US. individuals without evidence of
neurocysticercosis (clinical/serological/brain imaging). The sensitivity and
specificity of each antigen by WB were calculated by counting the number of true
positive, false positive, true negative and false negative results. Using the
receiver operating characteristic (ROC) curves, the cut-off values for the ELISA
and MBA were established as well as the sensitivity and specificity of each
assay. RESULTS: All three antigens showed a high sensitivity on WB in active NCC
cases with two or more viable cysts and low sensitivity for cases with single
viable cyst or calcified lesions and inactive NCC. WB showed the highest
specificity and sensitivity out of the three diagnostic techniques. The
recombinant T24H-his was the best diagnostic reagent in WB (100% sensitivity,
99.4% specificity), exhibiting similar results to the LLGP-EITB, against the same
panel of NCC sera. The GST-T24H antigen worked better than the others in ELISA
and MBA protocols (88.3 and 96.1% sensitivity, respectively and 96.5%
specificity). CONCLUSIONS: The sensitivity and specificity that we obtained were
similar to results from a previous study using a similar recombinant antigen
(rT24H), suggesting that recombinant antigens may be good alternatives to crude
extracts in a variety of diagnostic techniques. Furthermore, these antigens can
be applied in the development of point-of-care tests which would be useful in NCC
field studies.
PMID- 28506247
TI - Erratum to: Evaluation of a technology-enhanced integrated care model for frail
older persons: protocol of the SPEC study, a stepped-wedge cluster randomized
trial in nursing homes.
PMID- 28506246
TI - Vipie: web pipeline for parallel characterization of viral populations from
multiple NGS samples.
AB - BACKGROUND: Next generation sequencing (NGS) technology allows laboratories to
investigate virome composition in clinical and environmental samples in a culture
independent way. There is a need for bioinformatic tools capable of parallel
processing of virome sequencing data by exactly identical methods: this is
especially important in studies of multifactorial diseases, or in parallel
comparison of laboratory protocols. RESULTS: We have developed a web-based
application allowing direct upload of sequences from multiple virome samples
using custom parameters. The samples are then processed in parallel using an
identical protocol, and can be easily reanalyzed. The pipeline performs de-novo
assembly, taxonomic classification of viruses as well as sample analyses based on
user-defined grouping categories. Tables of virus abundance are produced from
cross-validation by remapping the sequencing reads to a union of all observed
reference viruses. In addition, read sets and reports are created after
processing unmapped reads against known human and bacterial ribosome references.
Secured interactive results are dynamically plotted with population and diversity
charts, clustered heatmaps and a sortable and searchable abundance table.
CONCLUSIONS: The Vipie web application is a unique tool for multi-sample
metagenomic analysis of viral data, producing searchable hits tables, interactive
population maps, alpha diversity measures and clustered heatmaps that are grouped
in applicable custom sample categories. Known references such as human genome and
bacterial ribosomal genes are optionally removed from unmapped ('dark matter')
reads. Secured results are accessible and shareable on modern browsers. Vipie is
a freely available web-based tool whose code is open source.
PMID- 28506248
TI - Paraquat and Parkinson's disease: a systematic review protocol according to the
OHAT approach for hazard identification.
AB - BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative condition
that has genetic susceptibility, aging, and exposure to certain chemicals as risk
factors. In recent decades, epidemiological and experimental studies have
investigated the role of pesticides in the development of PD, in particular that
of the herbicide paraquat. Here, we, therefore, aim to systematically review the
association between paraquat exposure and PD. METHODS: Observational studies
(cohort, case-control, and cross-sectional) eligible for this systematic review
will enroll any participant who was occupationally and/or environmentally exposed
to paraquat. Experimental studies, including in vivo and in vitro assays designed
to assess neurotoxicological endpoints or mechanisms of paraquat neurotoxicity,
will also be eligible. Outcomes of interest include the following: PD diagnosis;
neurobehavioral, biochemical, and/or morphological alterations; and cellular,
biochemical, and/or molecular pathways to oxidative stress. Using terms to
include all forms of paraquat combined with PD, the following electronic
databases will be searched: PubMed, EMBASE, LILACS, Toxnet, and Web of Science,
without restrictions as to language, year, or status of publication. A team of
reviewers will independently select potential titles and abstracts, extract data,
assess risk of bias, and determine the overall quality of evidence for each
outcome using the Office of Health Assessment and Translation (OHAT) approach for
systematic reviews and evidence integration. Dichotomous data will be summarized
as odds ratios, and continuous data will be given as mean differences, both with
their respective 95% confidence intervals. DISCUSSION: This is the first time
that the OHAT systematic review protocol will be applied to investigate a
possible causal association between exposure to paraquat and PD. Results from
this study could serve as basis for regulatory agencies to define paraquat levels
of concern, supporting its risk assessment process. SYSTEMATIC REVIEW
REGISTRATION: PROSPERO CRD42016050861.
PMID- 28506249
TI - An unusual case of proximal humeral simple bone cyst in an adult from secondary
cystic change.
AB - BACKGROUND: Simple bone cysts (SBC) have been documented to occur in adults with
closed physeal plates, most commonly affecting the calcaneus in this patient
subset. Although most authors theorize an association to trauma, etiology of
simple bone cysts remains an enigma up to now. CASE PRESENTATION: A 26-year-old
kickboxing coach sought consult for a painful right shoulder which on radiographs
and magnetic resonance (MR) imaging showed a proximal humeral lesion with signs
of ossification. The patient was lost to follow-up but again sought consult after
3 years for the recurring complaint. On repeat radiographs, computed tomography
(CT) scan, and MR images, tumor enlargement with cystic findings typical of
simple bone cyst were documented. Diagnostic aspiration of the lesion was firstly
done, revealing straw-colored fluid. The patient then underwent intralesional
curettage with alpha-tricalcium phosphate cement reconstruction of the lytic
defect. No perioperative complications were incurred, and on latest follow-up at
3 years postoperatively, Musculoskeletal Tumor Society (MSTS) and visual analog
scale (VAS) pain scores were 30/30 and 0/10, respectively. CONCLUSIONS: The
authors believe their report provides support to a possible association to trauma
of simple bone cysts occurring in the adult population with closed physes and
suggest this subset of patients may require a different treatment approach from
that for juvenile simple bone cysts.
PMID- 28506250
TI - Antimicrobial resistance profile of staphylococcus aureus isolates isolated from
ear discharges of patients at University of Hawassa comprehensive specialized
hospital.
AB - BACKGROUND: Drug-resistant microorganism are a growing global danger. Strains of
S. aureus have developed resistance to many commonly used antimicrobials due to
indiscriminate use of antimicrobials, and treatment becoming a challenge. Studies
assessing pattern and determinants of S. aureus resistance in ear infection in
Ethiopia are very scarce. This study presents overview of pattern and
determinants S. aureus resistance from samples of ear discharge in Ethiopia.
METHOD: A prospective cross-sectional study was conducted on patients who visit
ENT clinic of University of Hawassa comprehensive specialized hospital from
February 1, 2016 to November 1, 2016. 117 specimens were collected with sterile
applicator cotton swab from 117 patients with ear discharge visiting the clinic.
Data was fed and then edited, cleared, entered and analyzed using SPSS version
20. RESULT: The prevalence of S.aureus infection was 28.2%. S. aureus isolates
revealed up to 97.0% level of resistance pattern to the antimicrobials tested. In
the determination of the susceptibility of S. aureus on nine selected antibiotics
by disk diffusion technique, 97.0% of the isolates were resistant to cloxacilin
and 74.2% showed resistance to vancomycin. The overall rate of MDR was 100%, all
of the isolates were found to be resistant to more than two tested
antimicrobials. CONCLUSION: S. aureus has gotten frighteningly resistant to many
of common antimicrobials. Resistance rate to vancomyin is terrifyingly high. It
urges us to take measures to delay resistance. Emergence of resistance highlights
the value of prudent prescribing of antimicrobials and avoiding their irrational
use. Further researches focusing on identifying dynamics promoting resistance,
identifying high risk strains and molecular basis of resistance are required.
PMID- 28506252
TI - The impact of residential status on cognitive decline among older adults in
China: Results from a longitudinal study.
AB - BACKGROUND: Residential status has been linked to numerous determinants of health
and well-being. However, the influence of residential status on cognitive decline
remains unclear. The purpose of this research was to assess the changes of
cognitive function among older adults with different residential status (urban
residents, rural-to-urban residents, rural residents, and urban-to-rural
residents), over a 12-year period. METHODS: We used five waves of data (2002,
2005, 2008/2009, 2011/2012, and 2014) from the Chinese Longitudinal Healthy
Longevity Survey with 17,333 older adults age 65 and over who were interviewed up
to five times. Cognitive function was measured by the Mini Mental State
Examination (MMSE). Multilevel models were used regarding the effects of
residential status after adjusting for demographic characteristics, socioeconomic
factors, family support, health behaviors, and health status. RESULTS: After
controlling for covariates, significant differences in cognitive function were
found across the four groups: rural-to-urban and rural residents had a higher
level of cognition than urban residents at baseline. On average, cognitive
function decreased over the course of the study period. Rural-to-urban and rural
residents demonstrated a faster decline in cognitive function than urban
residents. CONCLUSIONS: This study suggests that residential status has an impact
on the rate of changes in cognition among older adults in China. Results from
this study provide directions for future research that addresses health
disparities, particularly in countries that are undergoing significant
socioeconomic transitions.
PMID- 28506251
TI - Diversity, in-vitro virulence traits and antifungal susceptibility pattern of
gastrointestinal yeast flora of healthy poultry, Gallus gallus domesticus.
AB - BACKGROUND: Poultry farming and consumption of poultry (Gallus gallus domesticus)
meat and eggs are common gastronomical practices worldwide. Till now, a detailed
understanding about the gut colonisation of Gallus gallus domesticus by yeasts
and their virulence properties and drug resistance patterns in available
literature remain sparse. This study was undertaken to explore this prevalent
issue. RESULTS: A total of 103 specimens of fresh droppings of broiler chickens
(commercial G domesticus) and domesticated chickens (domesticated G domesticus)
were collected from the breeding sites. The isolates comprised of 29 (33%)
Debaryozyma hansenii (Candida famata), 12 (13.6%) Sporothrix catenata (C.
ciferrii), 10 (11.4%) C. albicans, 8 (9.1%) Diutnia catenulata (C. catenulate), 6
(6.8%) C. tropicalis, 3 (3.4%) Candida acidothermophilum (C. krusei), 2 (2.3%) C.
pintolopesii, 1 (1.1%) C. parapsilosis, 9 (10.2%) Trichosporon spp. (T.
moniliiforme, T. asahii), 4 (4.5%) Geotrichum candidum, 3 (3.4%) Cryptococcus
macerans and 1 (1%) Cystobasidium minuta (Rhodotorula minuta). Virulence factors,
measured among different yeast species, showed wide variability. Biofilm cells
exhibited higher Minimum Inhibitory Concentration (MIC) values (MUg/ml) than
planktonic cells against all antifungal compounds tested: (fluconazole, 8-512 vs
0.031-16; amphotericin B, 0.5-64 vs 0.031-16; voriconazole 0.062-16 vs 0.062-8;
caspofungin, 0.062-4 vs 0.031-1). CONCLUSIONS: The present work extends the
current understanding of in vitro virulence factors and antifungal susceptibility
pattern of gastrointestinal yeast flora of G domesticus. More studies with
advanced techniques are needed to quantify the risk of spread of these potential
pathogens to environment and human.
PMID- 28506253
TI - Genome-wide identification of lncRNAs associated with chlorantraniliprole
resistance in diamondback moth Plutella xylostella (L.).
AB - BACKGROUND: Long noncoding RNAs (lncRNAs) are now considered important regulatory
factors, with a variety of biological functions in many species including
insects. Some lncRNAs have the ability to show rapid responses to diverse stimuli
or stress factors and are involved in responses to insecticide. However, there
are no reports to date on the characterization of lncRNAs associated with
chlorantraniliprole resistance in Plutella xylostella. RESULTS: Nine RNA
libraries constructed from one susceptible (CHS) and two chlorantraniliprole
resistant P. xylostella strains (CHR, ZZ) were sequenced, and 1309 lncRNAs were
identified, including 877 intergenic lncRNAs, 190 intronic lncRNAs, 76 anti-sense
lncRNAs and 166 sense-overlapping lncRNAs. Of the identified lncRNAs, 1059 were
novel. Furthermore, we found that 64 lncRNAs were differentially expressed
between CHR and CHS and 83 were differentially expressed between ZZ and CHS, of
which 22 were differentially expressed in both CHR and ZZ. Most of the
differentially expressed lncRNAs were hypothesized to be associated with
chlorantraniliprole resistance in P. xylostella. The targets of lncRNAs via cis-
(<10 kb upstream and downstream) or trans- (Pearson's correlation, r > 0.9 or <
0.9, P < 0.05) regulatory effects were also identified; many of the differently
expressed lncRNAs were correlated with various important protein-coding genes
involved in insecticide resistance, such as the ryanodine receptor, uridine
diphosphate glucuronosyltransferase (UGTs), cytochrome P450, esterase and the ATP
binding cassette transporter. CONCLUSIONS: Our results represent the first global
identification of lncRNAs associated with chlorantraniliprole resistance in P.
xylostella. These results will facilitate future studies of the regulatory
mechanisms of lncRNAs in chlorantraniliprole and other insecticide resistance and
in other biological processes in P. xylostella.
PMID- 28506254
TI - Reemergence of yellow fever in Ethiopia after 50 years, 2013: epidemiological and
entomological investigations.
AB - BACKGROUND: Yellow Fever (YF) is a viral hemorrhagic disease transmitted by aedes
mosquito species. Approximately, 200,000 cases and 30,000 deaths occur worldwide
every year. In Ethiopia, the last outbreak was reported in 1966 with 2200 cases
and 450 deaths. A number of cases with deaths from unknown febrile illness
reported from South Ari district starting from November 2012. This investigation
was conducted to identify the causative agent, source of the outbreak and
recommend appropriate interventions. METHODS: Medical records were reviewed and
Patients and clinicians involved in managing the case were interviewed.
Descriptive data analysis was done by time, person and place. Serum samples were
collected for serological analysis it was done using Enzyme-linked Immunosorbent
Assay for initial screening and confirmatory tests were done using Plaque
Reduction and Neutralization Test. Breteau and container indices were used for
the entomological investigation to determine the risk of epidemic. RESULTS: A
total of 141 Suspected YF cases with 43 deaths (CFR = 30.5%) were reported from
November 2012 to October 2013 from South Omo Zone. All age groups were affected
(mean 27.5, Range 1-75 Years). Of the total cases, 85.1% cases had jaundice and
56.7% cases had fever. Seven of the 21 samples were IgM positive for YF virus.
Aedes bromeliae and Aedes aegypti were identified as responsible vectors of YF in
affected area. The Breteau indices of Arkisha and Aykamer Kebeles were 44.4% and
33.3%, whereas the container indices were 12.9% and 22.2%, respectively.
CONCLUSION: The investigation revealed that YF outbreak was reemerged after 50
years in Ethiopia. Vaccination should be given for the affected and neighboring
districts and Case based surveillance should be initiated to detect every case.
PMID- 28506255
TI - Retrospective study of nonmucinous appendiceal adenocarcinomas: role of systemic
chemotherapy and cytoreductive surgery.
AB - BACKGROUND: Mucinous appendiceal adenocarcinomas (AAs) are the most common
histological subset of AAs. Nonmucinous AAs have been infrequently studied. We
performed a single-center retrospective study to investigate this histological
subtype. METHODS: We reviewed 172 patient records with nonmucinous AAs treated at
MD Anderson Cancer Center from Jan, 1990 to Jun, 2015 and recorded patient
demographics, tumor characteristics, treatment, and outcomes. Response rate (RR)
was assessed semi-quantitatively (response/no response) according to the treating
physician's findings. Survival outcomes were calculated using the Kaplan-Meier
product-limit method and compared using the log-rank test. RESULTS: Median age at
diagnosis was 52.9 years. Most patients presented with advanced-stage disease:
stage I-II (35%), stage III (15%), and stage IV (50%). Moderate and poorly
differentiated histology was seen in 56% and 44% tumors, respectively. Median
overall survival (OS) of all patients was stage-dependent and was 88.5, 39.2, and
28.3 months for stages I-II, stage III, and stage IV disease, respectively (p <
0.0001). In patients with metastatic disease, only 10% had extraperitoneal
disease without peritoneal involvement. Cytoreductive surgery (CRS) was attempted
in 31/69 (45%) patients with disease confined to the peritoneum. Complete CRS was
achieved in 18. Median OS for patients receiving complete CRS was 48.6 months.
Systemic chemotherapy was administered to 109 (86%) patients with metastatic
disease; a large majority of patients received either an oxaliplatin-based (55%)
or irinotecan-based (27%) regimen. Chemotherapy resulted in a semi-quantitative
RR of 54% and median time to progression (TTP) of 9.4 months (95% CI, 8.03
11.50). Patients who received combination chemotherapy (either oxaliplatin or
irinotecan-based) showed significantly longer median OS (p = 0.003), compared to
those receiving fluoropyrimidine monotherapy. CONCLUSIONS: This is one of the
first studies to report specifically on nonmucinous AAs. Nonmucinous AAs
presented with moderate or poorly differentiated histology with a predilection
for peritoneal metastasis. Systemic chemotherapy is active in this AA subtype.
Though CRS was infrequently used, complete CRS appears beneficial and warrants
further investigation.
PMID- 28506256
TI - AAV vector distribution in the mouse respiratory tract following four different
methods of administration.
AB - BACKGROUND: Targeted delivery of gene therapy vectors to the mouse respiratory
tract is often performed via intranasal or intratracheal administration; however,
there can be a great deal of variability between these methods, which could
potentially influence experimental results. Improving the accuracy and precision
of lung delivery will not only reduce the number of animals required to detect
statistically significant differences, but may reduce the variability of studies
from different laboratories. RESULTS: Here we evaluated three different methods
of adeno-associated virus (AAV) vector administration to the respiratory tract in
mice (intranasal, intubation, and intratracheal injection) and discuss the
advantages, challenges, and shortcomings of each. We also present a modified
intranasal delivery technique that is superior to passive administration of
vector into the nares of anesthetized supine animals. Transgene expression was
consistently visible in the nasal cavity, trachea, and proximal to middle aspect
of all lung lobes for all four methods, whereas transgene expression was
consistently observed in the most distal aspect of lung lobes only with the
intubation and intratracheal injection techniques. AAV vector genome copy numbers
in the lung were approximately four-fold lower in mice that received vector via
intranasal administration in comparison to the other three methods of vector
delivery. The modified intranasal, intubation and intratracheal injection methods
of vector administration did not yield statistical differences in AAV vector
genome copy numbers in the lung. With regard to reproducibility of vector
distribution within and between animals, the modified-intranasal technique was
superior. CONCLUSION: Our results show that mode of AAV vector administration to
the murine respiratory tract should be selected based on desired target site and
skill of the researcher, and that appropriate technique selection may greatly
influence experimental outcomes.
PMID- 28506258
TI - Health care waste management in community-based care: experiences of community
health workers in low resource communities in South Africa.
AB - BACKGROUND: In South Africa, community health workers (CHWs) working in community
based care (CBC) programmes provide care to patients most of whom are living with
HIV/AIDS and tuberculosis (TB). Although studies have shown that the caregiving
activities provided by the CHWs generate health care waste (HCW), there is
limited information about the experiences of CHWs on health care waste management
(HCWM) in CBC. This study explored HCWM in CBC in Durban, South Africa from the
perspectives CHWs. METHODS: We used three ethnographic approaches to collect
data: focus group discussions, participant observations and informal discussions.
Data was collected from 85 CHWs working in 29 communities in the Durban
metropolis, South Africa. Data collection took place from July 2013 to August
2014. RESULTS: CHWs provided nursing care activities to patients many of whom
were incontinent or bedridden. Some the patients were living with HIV/AIDS/TB,
stroke, diabetes, asthma, arthritis and high blood pressure. These caregiving
activities generate sharps and infectious waste but CHWs and family members did
not segregate HCW according to the risk posed as stipulated by the HCWM policy.
In addition, HCW was left with domestic waste. Major barriers to proper HCWM
identified by CHWs include, lack of assistance from family members in assisting
patients to use the toilet or change diapers and removing HCW from homes,
irregular waste collection by waste collectors, inadequate water for practicing
hygiene and sanitation, long distance between the house and the toilets and poor
conditions of communal toilets and pit latrines. As a result of these barriers,
HCW was illegally dumped along roads or in the bush, burnt openly and buried
within the yards. Liquid HCW such as vomit, urine and sputum were disposed in
open spaces near the homes. CONCLUSION: Current policies on primary health care
(PHC) and HCWM in South Africa have not paid attention to HCWM. Findings suggest
the need for primary health care reform to develop the competencies of CHWs in
HCWM. In addition, PHC and HCWM policies should address the infrastructure
deficit in low resource communities. In order for low-and-middle-income-countries
(LMICs) to develop effective community health worker programmes, there is a need
for synergies in PHC and HCWM policies.
PMID- 28506257
TI - An overview of systematic reviews of complementary and alternative therapies for
fibromyalgia using both AMSTAR and ROBIS as quality assessment tools.
AB - BACKGROUND: Fibromyalgia (FM) is a chronic, debilitating pain disorder.
Dissatisfaction with conventional medicine can lead people with FM to turn to
complementary and alternative medicine (CAM). Two previous overviews of
systematic reviews of CAM for FM have been published, but they did not assessed
for risk of bias in the review process. METHODS: Five databases Medline, Embase,
AMED (via OVID), Web of Science and Central were searched from their inception to
December 2015. Reference lists were hand-searched. We had two aims: the first was
to provide an up-to-date and rigorously conducted synthesis of systematic reviews
of CAM literature on FM; the second was to evaluate the quality of the available
systematic review evidence using two different tools: AMSTAR (Shea et al. BMC Med
Res Methodol 15; 7:10, 2007) and a more recently developed tool ROBIS (Whiting et
al. J Clin Epidemiol 69:225-34, 2016) specifically designed to assess risk of
bias in systematic reviews. Any review that assessed one of eight CAM therapies
for participants diagnosed with FM was considered. The individual studies had to
be randomised controlled trials where the intervention was compared to placebo,
treatment as usual or waitlist controls to be included. The primary outcome
measure was pain, and the secondary outcome measure was adverse events. RESULTS:
We identified 15 reviews that met inclusion criteria. There was low-quality
evidence that acupuncture improves pain compared to no treatment or standard
treatment, but good evidence that it is no better than sham acupuncture. The
evidence for homoeopathy, spinal manipulation and herbal medicine was limited.
CONCLUSIONS: Overall, five reviews scored 6 or above using the AMSTAR scale and
the inter-rater agreement was good (83.6%), whereas seven reviews achieved a low
risk of bias rating using ROBIS and the inter-rater agreement was fair (60.0%).
No firm conclusions were drawn for efficacy of either spinal manipulation or
homoeopathy for FM. There is limited evidence for topical Capsicum, but further
research is required. There is some evidence to support the effectiveness of
acupuncture for FM, but further high-quality trials are needed to investigate its
benefits, harms and mechanisms of action, compared with no or standard treatment.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016035846 .
PMID- 28506259
TI - Detection of antibacterial activities of Miswak, Kalonji and Aloe vera against
oral pathogens & anti-proliferative activity against cancer cell line.
AB - BACKGROUND: Emerging drug resistance and hindrance of treatment is provoking
scientists to search new, less expensive medicinally active compounds. Dental
diseases caused by oral pathogens are very frequent chronic infections around the
world. The medical potentials of a lot of Pakistani local herbs and herbal
combinations is relatively unknown, hence attempted to explore. A study was
designed to investigate potential role of local medicinal herbs for example
Miswak, Kalonji & Aloe vera as antimicrobial, antioxidant and anti-proliferative
agents against oral pathogens and cancer cell line. METHODS: Medicinal extracts
were prepared in solvents of different polarities. Their antimicrobial activity
was determined alone and in combination against oral pathogens. Antioxidant
activity was evaluated through Catalase and Superoxide dismutase assay and anti
proliferative activity was evaluated through 3-(4, 5-Dimethylthiazol-2-Yl)-2,5
Diphenyltetrazolium Bromide) assay. RESULTS: Plant extracts alone and in
combinations were found significantly effective as antimicrobial agent against
standard ATCC strains of C. albicans and S. aureus (P ?0.001). Especially Miwak
extract was found highly significant against fungus. Extracts of Kalonji were
found significant in inhibiting growth of HeLa cell lines. Miswak and Kalonji
showed significant levels of antioxidant activity. CONCLUSION: Medicinal herbs
Miswak and Kalonji have potential to be used for therapeutic purposes. Results
suggested that herbal medicinal composition can be prepared using these extracts
after applying scientific standardization methods.
PMID- 28506261
TI - A possible role of low regulatory T cells in anti-acetylcholine receptor antibody
positive myasthenia gravis after bone marrow transplantation.
AB - BACKGROUND: Chronic graft-versus-host disease (GVHD) appears several months
following allogenic hematopoietic stem cell transplantation (HSCT) and is
clinically analogous to autoimmune disorder. Polymyositis is a common
neuromuscular disorder in chronic GVHD, but myasthenia gravis (MG) is extremely
rare. Hence, its pathophysiology and treatment have not been elucidated. CASE
PRESENTATION: A 63-year-old man with a history of chronic GVHD presented with
ptosis, dropped head, and dyspnea on exertion, which had worsened over the
previous several months. He showed progressive decrement of compound muscle
action potential in the deltoid muscle evoked by 3-Hz repetitive nerve
stimulation, a positive edrophonium test, and elevated levels of serum anti
acetylcholine receptor antibodies, which suggested a diagnosis of generalized MG.
No thymoma was found. Flow cytometric analysis revealed a remarkable depletion of
peripheral Tregs (CD4+CD25highFOXP3+ cells, 0.24% of the total lymphocytes).
Administration of prednisolone and tacrolimus was insufficient to alleviate his
symptoms; however, the use of rituximab successfully improved his condition.
CONCLUSIONS: Myasthenic symptoms appeared in the process of tapering prednisolone
for the treatment of chronic GVHD, supporting the diagnosis of MG associated with
chronic GVHD. The present case proposes a possibility that reduction of Tregs
might contribute to the pathogenesis of MG underlying chronic GVHD. Immunotherapy
with rituximab is beneficial for treatment of refractory MG and GVHD.
PMID- 28506260
TI - Atypical retinal pigment epithelial defects with retained photoreceptor layers: a
so far disregarded finding in age related macular degeneration.
AB - BACKGROUND: To report patients with age-related macular degeneration and atypical
central retinal pigment epithelium (RPE) defects not attributable to geographic
atrophy (GA) or RPE-tears with overlying preserved photoreceptor layers. METHODS:
Multimodal imaging case-series evaluating the course of atypical RPE- defects in
patients with AMD using Color fundus images, Optical coherence tomography (OCT),
OCT-Angiography, fundus autofluorescence (FAF) and fluorescein-angiography (FA).
RESULTS: Ten patients were identified. Three patients had a prior RPE-rip and
were excluded. Seven patients with a mean follow-up period of 47 +/- 38 months
after the occurrence of the RPE-defect were included (age range 71-87 years).
Mean distance Best corrected visual acuity (BCVA) at initial presentation was
0.36 +/- 0.29logMAR and at last follow-up visit 0.51 +/- 0.43logMAR. Patients
presented with clinically apparent GA on funduscopy and FAF, but preserved
photoreceptor layers on optical coherence tomography (OCT). On FA there was early
hyperfluorescence and late pooling visible. Over time, migration of RPE/drusenoid
material right above the Bruch's membrane with concomitant decrease of
hypoautofluorescence was detectable in 4 cases. An enlargement of the RPE-defect
was apparent in the remaining 3 cases. The majority (n = 4) showed a drusenoid
pigment epithelium detachment (PED) preceding the lesion. CONCLUSIONS: Beside GA
and characteristic RPE-tears, another atypical form of RPE-defect with overlying
preserved photoreceptor layers are found in AMD. This so far disregarded subgroup
of patients present with reasonable visual function and long-term survival of
photoreceptors layers. Repair mechanisms such as ingrowth of RPE/drusenoid
material and persistent subretinal fluid (SRF), but also a RPE-independent visual
cycle for cone photopigment within the neurosensory retina may contribute to
their favorable course.
PMID- 28506262
TI - Identification and quantification of virulence factors of enterotoxigenic
Escherichia coli by high-resolution melting curve quantitative PCR.
AB - BACKGROUND: Diagnosis of enterotoxigenic E. coli (ETEC) associated diarrhea is
complicated by the diversity of E.coli virulence factors. This study developed a
multiplex quantitative PCR assay based on high-resolution melting curves analysis
(HRM-qPCR) to identify and quantify genes encoding five ETEC fimbriae related to
diarrhea in swine, i.e. K99, F41, F18, F6 and K88. METHODS: Five fimbriae
expressed by ETEC were amplified in multiple HRM-qPCR reactions to allow
simultaneous identification and quantification of five target genes. The assay
was calibrated to allow quantification of the most abundant target gene, and
validated by analysis of 30 samples obtained from piglets with diarrhea and
healthy controls, and comparison to standard qPCR detection. RESULTS: The five
amplicons with melting temperatures (Tm) ranging from 74.7 +/- 0.06 to 80.5 +/-
0.15 degrees C were well-separated by HRM-qPCR. The area of amplicons under the
melting peak correlated linearly to the proportion of the template in the
calibration mixture if the proportion exceeded 4.8% (K88) or <1% (all other
amplicons). The suitability of the method was evaluated using 30 samples from
weaned pigs aged 6-7 weeks; 14 of these animals suffered from diarrhea in
consequence of poor sanitary conditions. Genes encoding fimbriae and enterotoxins
were quantified by HRM-qPCR and/or qPCR. The multiplex HRM-qPCR allowed accurate
analysis when the total gene copy number of targets was more than 1 * 105 / g wet
feces and the HRM curves were able to simultaneously distinguish fimbriae genes
in the fecal samples. The relative quantification of the most abundant F18 based
on melting peak area was highly correlated (P < 0.001; r2 = 0.956) with that of
individual qPCR result but the correlation for less abundant fimbriae was much
lower. CONCLUSIONS: The multiplex HRM assay identifies ETEC virulence factors
specifically and efficiently. It correctly indicated the predominant fimbriae
type and additionally provides information of presence/ absence of other fimbriae
types and it could find broad applications for pathogen diagnosis.
PMID- 28506263
TI - Mindfulness-based stress reduction in Parkinson's disease: a systematic review.
AB - BACKGROUND: Mindfulness based stress reduction (MBSR) is increasingly being used
to improve outcomes such as stress and depression in a range of long-term
conditions (LTCs). While systematic reviews on MBSR have taken place for a number
of conditions there remains limited information on its impact on individuals with
Parkinson's disease (PD). METHODS: Medline, Central, Embase, Amed, CINAHAL were
searched in March 2016. These databases were searched using a combination of MeSH
subject headings where available and keywords in the title and abstracts. We also
searched the reference lists of related reviews. Study quality was assessed based
on questions from the Cochrane Collaboration risk of bias tool. RESULTS: Two
interventions and three papers with a total of 66 participants were included. The
interventions were undertaken in Belgium (n = 27) and the USA (n = 39). One study
reported significantly increased grey matter density (GMD) in the brains of the
MBSR group compared to the usual care group. Significant improvements were
reported in one study for a number of outcomes including PD outcomes, depression,
mindfulness, and quality of life indicators. Only one intervention was of
reasonable quality and both interventions failed to control for potential
confounders in the analysis. Adverse events and reasons for drop-outs were not
reported. There was also no reporting on the costs/benefits of the intervention
or how they affected health service utilisation. CONCLUSION: This systematic
review found limited and inconclusive evidence of the effectiveness of MBSR for
PD patients. Both of the included interventions claimed positive effects for PD
patients but significant outcomes were often contradicted by other results.
Further trials with larger sample sizes, control groups and longer follow-ups are
needed before the evidence for MBSR in PD can be conclusively judged.
PMID- 28506264
TI - An association between pulmonary Mycobacterium avium-intracellulare complex
infections and biomarkers of Th2-type inflammation.
AB - BACKGROUND: The rising incidence of pulmonary Mycobacterium avium-intracellulare
complex (MAI) infection is unexplained but parallels the growing world-wide
epidemic of allergic disease. We hypothesized an association between pulmonary
MAI infection and Th2-type immune responses as seen in allergy. METHODS:
Biomarkers of patient Th2-type immune responses (peripheral blood eosinophil
counts and serum IgE levels) were compared between patients with positive
pulmonary samples for tuberculosis and non-tuberculous mycobacterial (NTM)
infection. A further comparison of clinical characteristics, including
respiratory co-morbidities, and biomarkers, was conducted between patients
culturing MAI NTM and those culturing NTM other than MAI. RESULTS: Patients
culturing NTM from pulmonary samples had significantly higher peripheral blood
eosinophil levels than those culturing Mycobacterium tuberculosis. Furthermore,
patients culturing MAI compared to those culturing NTM other than MAI had higher
eosinophil counts (mean 0.29x109/L vs 0.15x109/L, p = 0.010) and IgE levels
(geometric mean 138kU/L vs 47kU/L, p = 0.021). However there was no significant
difference in the frequency of asthma between the two NTM groups. CONCLUSIONS:
There is an association between biomarkers of Th2-type immune responses and
pulmonary MAI. Prospective and translational research could identify the
direction of causation; and so determine whether our finding may be utilized
within future management strategies for MAI.
PMID- 28506265
TI - Determinants of poor utilization of antenatal care services among recently
delivered women in Rwanda; a population based study.
AB - BACKGROUND: In Rwanda, a majority of pregnant women visit antenatal care (ANC)
services, however not to the extent that is recommended. Association between
socio-demographic or psychosocial factors and poor utilization of antenatal care
services (<=2 visits during the course of pregnancy irrespective of the timing)
among recently pregnant women in Rwanda were investigated. METHODS: This
population-based, cross sectional study included 921 women who gave birth within
the past 13 months. Data was obtained using an interviewer-administered
questionnaire. For the analyses, bi-and multivariable logistic regression was
used and odds ratios were presented with their 95% confidence intervals. RESULTS:
About 54% of pregnant women did not make the recommended four visits to ANC
during pregnancy. The risk of poor utilization of ANC services was higher among
women aged 31 years or older (AOR, 1.78; 95% CI: 1.14, 2.78), among single women
(AOR, 2.99; 95% CI: 1.83, 4.75) and women with poor social support (AOR, 1.71;
95% CI: 1.09, 2.67). No significant associations were found for school attendance
or household assets (proxy for socio-economic status) with poor utilization of
ANC services. CONCLUSION: Older age, being single, divorced or widowed and poor
social support were associated with poor utilization of ANC services. General
awareness in communities should be raised on the importance of the number and
timing of ANC visits. ANC clinics should further be easier to access, transport
should be available, costs minimized and opening hours may be extended to
facilitate visits for pregnant women.
PMID- 28506267
TI - A qualitative study on acceptable levels of risk for pregnant women in clinical
research.
AB - BACKGROUND: There is ambiguity with regard to what counts as an acceptable level
of risk in clinical research in pregnant women and there is no input from
stakeholders relative to such research risks. The aim of our paper was to explore
what stakeholders who are actively involved in the conduct of clinical research
in pregnant women deem an acceptable level of risk for pregnant women in clinical
research. Accordingly, we used the APOSTEL VI study, a low-risk obstetrical
randomised controlled trial, as a case-study. METHODS: We conducted a prospective
qualitative study using 35 in-depth semi-structured interviews and one focus
group. We interviewed healthcare professionals, Research Ethics Committee members
(RECs) and regulators who are actively involved in the conduct of clinical
research in pregnant women, in addition to pregnant women recruited for the
APOSTEL VI case-study in the Netherlands. RESULTS: Three themes characterise the
way stakeholders view risks in clinical research in pregnant women in general.
Additionally, one theme characterises the way healthcare professionals and
pregnant women view risks with respect to the case-study specifically. First,
ideas on what constitutes an acceptable level of risk in general ranged from a
preference for zero risk for the foetus up to minimal risk. Second, the
desirability of clinical research in pregnant women in general was questioned
altogether. Third, stakeholders proposed to establish an upper limit of risk in
potentially beneficial clinical research in pregnant women in order to protect
the foetus and the pregnant woman from harm. Fourth and finally, the case-study
illustrates that healthcare professionals' individual perception of risk may
influence recruitment. CONCLUSIONS: Healthcare professionals, RECs, regulators
and pregnant women are all risk adverse in practice, possibly explaining the
continuing underrepresentation of pregnant women in clinical research.
Determining the acceptable levels of risk on a universal level alone is
insufficient, because the individual perception of risk also influences behaviour
towards pregnant women in clinical research. Therefore, bioethicists and
researchers might be interested in changing the perception of risk, which could
be achieved by education and awareness about the actual benefits and harms of
inclusion and exclusion of pregnant women.
PMID- 28506266
TI - Impact of preterm birth on infant mortality for newborns with congenital heart
defects: The EPICARD population-based cohort study.
AB - BACKGROUND: Congenital heart defects (CHD) and preterm birth (PTB) are major
causes of infant mortality. However, limited data exist on risk of mortality
associated with PTB for newborns with CHD. Our objective was to assess impact of
PTB on risk of infant mortality for newborns with CHD, while taking into account
the role of associated anomalies and other potentially confounding factors.
METHODS: We used data on 2172 live births from a prospective population-based
cohort study of CHD (the EPICARD Study) and compared neonatal, post-neonatal and
overall infant mortality for infants born at <32, 32-34 and 35-36 weeks vs. those
born at term (37-41 weeks). RESULTS: Preterm newborns had a 3.8-fold higher risk
of infant death (17.9%) than term newborns (4.7%), RR 3.8, 95%CI 2.7-5.2; the
risk associated with PTB was more than four-fold higher for neonatal (RR 4.3, 95%
CI 2.9-6.6) and three-fold higher for post-neonatal deaths (RR 3.0, 95% CI 1.7
5.2). Survival analysis showed that newborns <35 weeks had a higher risk of
mortality, which decreased but persisted after exclusion of associated anomalies
and adjustment for potential confounders. CONCLUSIONS: Preterm birth is
associated with an approximately four-fold higher risk of infant mortality for
newborns with CHD. This excess risk appears to be mostly limited to newborns <35
weeks of gestation and is disproportionately due to early deaths.
PMID- 28506268
TI - Ethnic differences in folic acid supplement use in a population-based cohort of
pregnant women in Norway.
AB - BACKGROUND: Peri-conceptional use of folic acid supplements is recommended to
prevent neural tube defects. Correct supplement use seems to be less common among
ethnic minorities. We examined ethnic differences in folic acid supplement use
before and during pregnancy and possible effect modification by education or
planning of pregnancy. METHODS: The participants were 811 healthy pregnant women
from a population-based cohort study in Oslo, Norway in 2008-2010. Ethnicity was
categorized to five groups (European, Middle Eastern, South Asian, East Asian,
African). Data on folic acid supplement use were obtained from hospital records
and remaining data by a questionnaire. Logistic regression analyses were adjusted
for age, parity, planning of pregnancy, education and Norwegian language skills.
RESULTS: Before pregnancy, 30.1% of European women and 7.1 to 13.6% of women in
the other ethnic groups used folic acid supplements (p < 0.001). The adjusted
odds ratio (OR) for supplement use was 0.55 (95% confidence interval 0.31; 0.96)
for South Asian and 0.42 (95% confidence interval 0.19; 0.94) for Middle Eastern
women compared with European women. During pregnancy, supplement use was most
common in European women (65.7%) and least common in Middle Eastern (29.4%) and
African women (29.0%) (p < 0.001). Compared with European women, all other ethnic
groups had lower adjusted odds (OR 0.30 to 0.50, p < 0.05 for all) for supplement
use among women with high school or less education, but not among more educated
women. Planning of pregnancy did not modify the association between ethnicity and
supplement use. CONCLUSIONS: Few women used folic acid supplements before
pregnancy. Educational level modified the association between ethnicity and
supplement use during pregnancy. Public health campaigns should focus on
increasing awareness especially in ethnic minority groups with low educational
level.
PMID- 28506270
TI - Predictors of preferred location of care in middle-aged individuals of a
municipality in Japan: a cross-sectional survey.
AB - BACKGROUND: Japan has the highest rate of aging. To contain Long-Term Care (LTC)
Insurance costs, the Japanese government is attempting to increase the proportion
of individuals receiving home care services. However, demand for institutional
care is increasing. These circumstances will decrease the sustainability of the
LTC Insurance System. The objective of the present study was to identify
predictors of the location of preference for LTC (home or a facility) in middle
aged individuals in a municipality. METHODS: This was a cross-sectional study of
middle-aged individuals (n = 906) in Tsukuba, Japan. Data primarily included
individual or social factors (sex, age, household size, experience with caring
for family, information sources about social services or municipality policy),
factors about care prevention (self-reported health, efforts to promote health,
motivation in life), and the preferred location of care. These variables were
analysed with multiple logistic regression, using preferred location of care as
the dependent variable. RESULTS: A total of 693 respondents were analysed. Of
these, 440 (63.5%) preferred home and 253 (36.5%) preferred a facility. The
results of logistic regression analysis showed that a preference for facility was
significantly associated with female sex, younger age, experience with caring for
family, fewer information sources about social services or municipality policies,
selecting 'go to culture lessons/study to satisfy interests', and not selecting
'spending time happily with family' under motivation in life. CONCLUSIONS: To
support the selection of receiving home care services, municipalities must
consider improving policies that reduce the burdens of present middle-aged
caregivers, and promote the provision of care service information from multiple
sources.
PMID- 28506269
TI - The emerging roles and therapeutic potential of exosomes in epithelial ovarian
cancer.
AB - Ovarian cancer (OC) is one of the three types of malignant tumors in the female
reproductive system, and epithelial ovarian cancer (EOC) is its most typical
form. Due to the asymptomatic nature of the early stages and resistance to
chemotherapy, EOC has both a poor prognosis and a high fatality rate. Current
treatments for OC are very limited, and the 5-years survival rate is
approximately 30%. Exosomes, which are microvesicles ranging from approximately
30-100 nm in size that are secreted by living cells, can be produced from
different cell types and detected in various body fluids. Cancer cells can
secrete more exosomes than healthy cells, and more importantly, the content of
cancer cell-derived exosomes is distinct. The exosomes shedding from tumor cells
are considered to be involved in tumor progression and metastasis. As such,
exosomes are expected to be potential tools for tumor diagnosis and treatment. In
this review, we briefly present the emerging roles of exosomes in OC and
summarize related articles about their roles as diagnostic or prognostic
biomarkers and in the treatment and drug resistance of OC.
PMID- 28506271
TI - Agrobiodiversity and in situ conservation in ethnic minority communities of
Xishuangbanna in Yunnan Province, Southwest China.
AB - BACKGROUND: Xishuangbanna of Yunnan Province, southwest of China belongs to a
global biodiversity and cultural hotspot. Agrobiodiversity plays an essential
role in local livelihoods and traditional culture in the region. However,
preliminary studies suggest that diversity of crop plants and livestock species
is declining. We hypothesized that agrobiodiversity and traditional means of
preserving agrobiodiversity are threatened because of changes in government
policy in favor of commercial plantations, land use change and changes in
traditional agricultural practices. We investigated whether or not
agrobiodiversity was declining, the specific causes, and signs of active
biodiversity conservation practices in ethnic minority communities of
Xishuangbanna which could form the basis for extensive in situ conservation
programmes. METHODS: A series of field studies to document trends in
agrobiodiversity were conducted in different ethnic minority communities in
Menghai County, Mengla County and Jinghong City of Xishuangbanna of Yunnan
Province, southwest of China between July 2015 and February 2016. Data was
obtained through the use of semi-structured questionnaires, field observation and
participatory rural appraisal (PRA) tools. A total of 360 ethnic households
provided information on current status, functions, characteristics, changes, and
threatened factors of farming crop and livestock resources. Some measures for in
situ conservation of agricultural biological resources were also researched using
PRA methods. RESULTS: Two hundred twenty-six crop varieties belonging to 31
families, 71 genera and 101 species were identified in Xishuangbanna, which
included 83 vegetable crops, 77 food crops, 24 spice crops, 22 fruit crops, 13
cash crops, 6 oil crops, and 1 cloth crop, respectively. There were 15 livestock
varieties, belonging to 6 major species: cattle, pigs, goats, chickens, ducks,
and geese. Different crop and livestock resources had their own characteristics,
functions and threatened factors. Since 2002, agroecosystem, crop diversity and
livestock diversity have declined greatly over the Xishuangbanna region as a
whole under implementation of the Sloping Land Conversion Program (SLCP). Swidden
agriculture was completely eliminated under this program and gradually replaced
by large land areas devoted to rubber, tea and banana plantations. Villager
numbers engaging in farming production and population of crops and livestock were
greatly decreased, particularly in terms of production of local traditional
varieties. However, some in situ conservation measures such as seeds
preservation, planting of traditional crops and raising livestock have played an
important role in local agrobiodiversity conservation. CONCLUSION: Abundant
agricultural resources and agrobiodiversity are critical to the local livelihood
and maintenance of traditional culture in Xishuangbanna. However,
agrobiodiversity and related traditional culture have been greatly impacted by
implementation of the SLCP since 2002. Therefore, in future conservation of
agrobiodiversity, incorporating some sustainable protection measures based in
local communities such as convening seed exchange fairs, conserving traditional
varieties in permanent plots, making a visual documentary of indigenous
cultivation, and providing traditional agricultural products to tourists should
be carefully considered and adopted.
PMID- 28506272
TI - Prevalence and clonal relationship of ESBL-producing Salmonella strains from
humans and poultry in northeastern Algeria.
AB - BACKGROUND: The aims of this study were to investigate Salmonella contamination
in broiler chicken farms and slaughterhouses, to assess the antibiotic resistance
profile in avian and human Salmonella isolates, and to evaluate the relationship
between avian and human Extended Spectrum beta-Lactamase (ESBL)-producing
isolates. Salmonella was screened in different sample matrices collected at
thirty-two chicken farms and five slaughterhouses. The human isolates were
recovered from clinical specimens at the University Teaching Hospital of
Constantine (UTH). All suspected colonies were confirmed by MALDI-TOF (Matrix
Assisted Laser Desorption Ionization Time OF light) and serotyped. Susceptibility
testing against 13 antibiotics including, amoxicillin/clavulanic acid,
ticarcillin, cefoxitin, cefotaxime, aztreonam, imipenem, ertapenem, gentamicin,
amikacin, ciprofloxacin, colistin, trimethoprim/sulfamethoxazole and fosfomycin,
was performed using the disk diffusion method on Mueller-Hinton agar. ESBL
production was screened by the double-disk synergy test and confirmed by
molecular characterization using PCR (polymerase chain reaction) amplification
and sequencing of ESBL encoding genes. Clonality of the avian and human strains
was performed using the Multi Locus Sequencing Typing method (MLST). RESULTS:
Forty-five isolated avian Salmonella strains and 37 human collected ones were
studied. Five S. enterica serotypes were found in avian isolates (mainly
Kentucky) and 9 from human ones (essentially Infantis). 51.11% and 26.6% of the
avian isolates were resistant to ciprofloxacin and cefotaxime, respectively,
whereas human isolates were less resistant to these antibiotics (13.5% to
ciprofloxacin and 16.2% to cefotaxime). Eighteen (12 avian and 6 human) strains
were found to produce ESBLs, which were identified as bla CTX-M-1 (n = 12), bla
CTX-M-15 (n = 5) and bla TEM group (n = 8). Interestingly, seven of the ESBL
producing strains (5 avian and 2 human) were of the same ST (ST15) and clustered
together, suggesting a common origin. CONCLUSION: The results of the combined
phenotypic and genotypic analysis found in this study suggest a close
relationship between human and avian strains and support the hypothesis that
poultry production may play a role in the spread of multidrug-resistant
Salmonella in the human community within the study region.
PMID- 28506273
TI - Inertial measurement systems for segments and joints kinematics assessment:
towards an understanding of the variations in sensors accuracy.
AB - BACKGROUND: Joints kinematics assessment based on inertial measurement systems,
which include attitude and heading reference system (AHRS), are quickly gaining
in popularity for research and clinical applications. The variety of the tasks
and contexts they are used in require a deep understanding of the AHRS accuracy
for optimal data interpretation. However, published accuracy studies on AHRS are
mostly limited to a single task measured on a limited number of segments and
participants. This study assessed AHRS sensors kinematics accuracy at multiple
segments and joints through a variety of tasks not only to characterize the
system's accuracy in these specific conditions, but also to extrapolate the
accuracy results to a broader range of conditions using the characteristics of
the movements (i.e. velocity and type of motion). Twenty asymptomatic adults
([Formula: see text] = 49.9) performed multiple 5 m timed up and go.
Participants' head, upper trunk, pelvis, thigh, shank and foot were
simultaneously tracked using AHRS and an optical motion capture system (gold
standard). Each trial was segmented into basic tasks (sit-to-stand, walk, turn).
RESULTS: At segment level, results revealed a mean root-mean-squared-difference
[Formula: see text] varying between 1.1 degrees and 5.5 degrees according to
the segment tracked and the task performed, with a good to excellent agreement
between the systems. Relative sensor kinematics accuracy (i.e. joint) varied
between 1.6 degrees and 13.6 degrees over the same tasks. On a global scheme,
analysis of the effect of velocity on sensor kinematics accuracy showed that AHRS
are better adapted to motions performed between 50 degrees /s and 75 degrees /s
(roughly thigh and shank while walking). CONCLUSION: Results confirmed that
pairing of modules to obtain joint kinematics affects the accuracy compared to
segment kinematics. Overall, AHRS are a suitable solution for clinical evaluation
of biomechanics under the multi-segment tasks performed although the variation in
accuracy should be taken into consideration when judging the clinical
meaningfulness of the observed changes.
PMID- 28506274
TI - Contextual and psychosocial factors predicting Ebola prevention behaviours using
the RANAS approach to behaviour change in Guinea-Bissau.
AB - BACKGROUND: The outbreak of the Ebola virus disease (EVD) in West Africa in
December 2013 was the largest Ebola outbreak in history. This study aimed to
measure the underlying contextual and psychosocial factors of intentions to
perform Ebola prevention behaviours (not touching people who might be suffering
from Ebola, reporting suspected cases to the National Ebola Hotline, NEH) in
Guinea-Bissau. Geographical location, cross-border market activities, poor water,
sanitation and hygiene (WASH) conditions, and burial practices in some
communities pose a serious risk in terms of potential EVD outbreak and seriously
hamper its prevention in Guinea-Bissau. METHODS: In July and August 2015,
quantitative data from 1369 respondents were gathered by structured face-to-face
interviews. The questionnaire was based on the psychosocial factors of the RANAS
(risks, attitudes, norms, abilities, and self-regulation) model. Data were
analyzed by multiple linear regression analyses. RESULTS: The most important
predictors for the intention to call the NEH were believing that calling the
Hotline would help the infected person, perceiving that important members from
the household approve of calling the Hotline, thinking that calling the Hotline
is something they should do, and believing that it is important to call the
Hotline to report a suspected case. For the intention not to touch someone who
might be suffering from Ebola, the most important predictors were health
knowledge, the perception of risk with regard to touching a person who might be
suffering from Ebola, and the belief that they were able not to touch a possibly
infected person. Age in years was the only significant contextual predictor for
one of the two behavioural intentions, the intention to call the Hotline. It
seems that younger people are more likely to use a service like the NEH than
older people. CONCLUSIONS: Strengths and gaps were identified in the study
population in relation to the intention to perform prevention behaviours. These
call for innovative ways of aligning existing hygiene programs with relevant
psychosocial factors. This research is relevant to further outbreaks of
contagious diseases as it sheds light on important aspects of the impact of
public health interventions during emergencies and epidemics.
PMID- 28506276
TI - Redo coronary bypass grafting for congenital left main coronary atresia: a case
report.
AB - BACKGROUND: Congenital left main coronary atresia is an extremely rare coronary
anomaly. Long-term surgical outcomes and the optimal management strategies for
recurrence of ischemia remain uncertain. Herein, we present a case involving
successful redo coronary artery bypass grafting for unstable angina 27 years
after the initial coronary artery bypass grafting for congenital left main
coronary atresia. CASE PRESENTATION: A 33-year-old woman was referred to our
department with unstable angina. At the age of 6, she had undergone coronary
artery bypass grafting of the second diagonal branch using the left internal
thoracic artery and the obtuse marginal branch using saphenous vein grafting for
left main coronary atresia. Although a coronary angiogram showed a patent left
internal thoracic artery graft to the second diagonal branch and a patent
saphenous vein graft to the obtuse marginal branch, the left anterior descending
artery was not being perfused by the grafts because of a disruption of blood flow
to the left anterior descending artery from the left internal thoracic artery.
Therefore, we performed a redo coronary artery bypass grafting using the in situ
right internal thoracic artery to the first diagonal branch, which was to be
connected to the left anterior descending artery, resulting in amelioration of
the ischemia of the left anterior wall. The patient was discharged 10 days after
the operation and has been in good health for over 3 years without recurrence of
chest symptoms. CONCLUSIONS: Coronary revascularization using a saphenous vein
and left internal thoracic artery grafts is effective in achieving an adequate
blood supply to the distal coronary arteries, and this effect can last for
decades. However, careful follow-up is necessary because recurrent myocardial
ischemia due to the development of a coronary artery occlusion may occur in
adulthood.
PMID- 28506275
TI - Global survey of malaria rapid diagnostic test (RDT) sales, procurement and lot
verification practices: assessing the use of the WHO-FIND Malaria RDT Evaluation
Programme (2011-2014).
AB - BACKGROUND: Malaria rapid diagnostic tests (RDTs) play a critical role in malaria
case management, and assurance of quality is a key factor to promote good
adherence to test results. Since 2007, the World Health Organization (WHO) and
the Foundation for Innovative New Diagnostics (FIND) have coordinated a Malaria
RDT Evaluation Programme, comprising a pre-purchase performance evaluation
(product testing, PT) and a pre-distribution quality control of lots (lot
testing, LT), the former being the basis of WHO recommendations for RDT
procurement. Comprehensive information on malaria RDTs sold worldwide based on
manufacturers' data and linked to independent performance data is currently not
available, and detailed knowledge of procurement practices remains limited.
METHODS: The use of the PT/LT Programme results as well as procurement and lot
verification practices were assessed through a large-scale survey, gathering
product-specific RDT sales and procurement data (2011-14 period) from a total of
32 manufacturers, 12 procurers and 68 National Malaria Control Programmes
(NMCPs). RESULTS: Manufacturers' reports showed that RDT sales had more than
doubled over the four years, and confirmed a trend towards increased compliance
with the WHO procurement criteria (from 83% in 2011 to 93% in 2014). Country
level reports indicated that 74% of NMCPs procured only 'WHO-compliant' RDT
products, although procurers' transactions datasets revealed a surprisingly
frequent overlap of different products and even product types (e.g., Plasmodium
falciparum-only and Plasmodium-pan) in the same year and country (60 and 46% of
countries, respectively). Importantly, the proportion of 'non-complying' (i.e.,
PT low scored or not evaluated) products was found to be higher in the private
health care sector than in the public sector (32% vs 5%), and increasing over
time (from 22% of private sector sales in 2011 to 39% in 2014). An estimated 70%
of the RDT market was covered by the LT programme. The opinion about the PT/LT
Programmes was positive overall, and quality of RDTs as per the PT Programme was
rated as the number one procurement criteria. CONCLUSIONS: This survey provided
in-depth information on RDT sales and procurement dynamics, including the largely
unstudied private sector, and demonstrated how the WHO-FIND Programme has
positively influenced procurement practices in the public sector.
PMID- 28506277
TI - Quantifying the mapping precision of genome-wide association studies using whole
genome sequencing data.
AB - BACKGROUND: Understanding the mapping precision of genome-wide association
studies (GWAS), that is the physical distances between the top associated single
nucleotide polymorphisms (SNPs) and the causal variants, is essential to design
fine-mapping experiments for complex traits and diseases. RESULTS: Using
simulations based on whole-genome sequencing (WGS) data from 3642 unrelated
individuals of European descent, we show that the association signals at rare
causal variants (minor allele frequency <= 0.01) are very unlikely to be mapped
to common variants in GWAS using either WGS data or imputed data and vice versa.
We predict that at least 80% of the common variants identified from published
GWAS using imputed data are within 33.5 Kbp of the causal variants, a resolution
that is comparable with that using WGS data. Mapping precision at these loci will
improve with increasing sample sizes of GWAS in the future. For rare variants,
the mapping precision of GWAS using WGS data is extremely high, suggesting WGS is
an efficient strategy to detect and fine-map rare variants simultaneously. We
further assess the mapping precision by linkage disequilibrium between GWAS hits
and causal variants and develop an online tool (gwasMP) to query our results with
different thresholds of physical distance and/or linkage disequilibrium (
http://cnsgenomics.com/shiny/gwasMP ). CONCLUSIONS: Our findings provide a
benchmark to inform future design and development of fine-mapping experiments and
technologies to pinpoint the causal variants at GWAS loci.
PMID- 28506278
TI - A framework for evaluating epidemic forecasts.
AB - BACKGROUND: Over the past few decades, numerous forecasting methods have been
proposed in the field of epidemic forecasting. Such methods can be classified
into different categories such as deterministic vs. probabilistic, comparative
methods vs. generative methods, and so on. In some of the more popular
comparative methods, researchers compare observed epidemiological data from the
early stages of an outbreak with the output of proposed models to forecast the
future trend and prevalence of the pandemic. A significant problem in this area
is the lack of standard well-defined evaluation measures to select the best
algorithm among different ones, as well as for selecting the best possible
configuration for a particular algorithm. RESULTS: In this paper we present an
evaluation framework which allows for combining different features, error
measures, and ranking schema to evaluate forecasts. We describe the various
epidemic features (Epi-features) included to characterize the output of
forecasting methods and provide suitable error measures that could be used to
evaluate the accuracy of the methods with respect to these Epi-features. We focus
on long-term predictions rather than short-term forecasting and demonstrate the
utility of the framework by evaluating six forecasting methods for predicting
influenza in the United States. Our results demonstrate that different error
measures lead to different rankings even for a single Epi-feature. Further, our
experimental analyses show that no single method dominates the rest in predicting
all Epi-features when evaluated across error measures. As an alternative, we
provide various Consensus Ranking schema that summarize individual rankings, thus
accounting for different error measures. Since each Epi-feature presents a
different aspect of the epidemic, multiple methods need to be combined to provide
a comprehensive forecast. Thus we call for a more nuanced approach while
evaluating epidemic forecasts and we believe that a comprehensive evaluation
framework, as presented in this paper, will add value to the computational
epidemiology community.
PMID- 28506279
TI - Uncovering the trimethylamine-producing bacteria of the human gut microbiota.
AB - BACKGROUND: Trimethylamine (TMA), produced by the gut microbiota from dietary
quaternary amines (mainly choline and carnitine), is associated with
atherosclerosis and severe cardiovascular disease. Currently, little information
on the composition of TMA producers in the gut is available due to their low
abundance and the requirement of specific functional-based detection methods as
many taxa show disparate abilities to produce that compound. RESULTS: In order to
examine the TMA-forming potential of microbial communities, we established
databases for the key genes of the main TMA-synthesis pathways, encoding choline
TMA-lyase (cutC) and carnitine oxygenase (cntA), using a multi-level screening
approach on 67,134 genomes revealing 1107 and 6738 candidates to exhibit cutC and
cntA, respectively. Gene-targeted assays enumerating the TMA-producing community
by quantitative PCR and characterizing its composition via Illumina sequencing
were developed and applied on human fecal samples (n = 50) where all samples
contained potential TMA producers (cutC was detected in all individuals, whereas
only 26% harbored cntA) constituting, however, only a minor part of the total
community (below 1% in most samples). Obtained cutC amplicons were associated
with various taxa, in particular with Clostridium XIVa strains and Eubacterium
sp. strain AB3007, though a bulk of sequences displayed low nucleotide identities
to references (average 86% +/- 7%) indicating that key human TMA producers are
yet to be isolated. Co-occurrence analysis revealed specific groups governing the
community structure of cutC-exhibiting taxa across samples. CntA amplicons
displayed high identities (~99%) to Gammaproteobacteria-derived references,
primarily from Escherichia coli. Metagenomic analysis of samples provided by the
Human Microbiome Project (n = 154) confirmed the abundance patterns as well as
overall taxonomic compositions obtained with our assays, though at much lower
resolution, whereas 16S ribosomal RNA gene sequence analysis could not adequately
uncover the TMA-producing potential. CONCLUSIONS: In this study, we developed a
diagnostic framework that enabled the quantification and comprehensive
characterization of the TMA-producing potential in human fecal samples. The key
players were identified, and together with predictions on their environmental
niches using functional genomics on most closely related reference strains, we
provide crucial information for the development of specific treatment strategies
to restrain TMA producers and limit their proliferation.
PMID- 28506280
TI - OptiMouse: a comprehensive open source program for reliable detection and
analysis of mouse body and nose positions.
AB - BACKGROUND: Accurate determination of mouse positions from video data is crucial
for various types of behavioral analyses. While detection of body positions is
straightforward, the correct identification of nose positions, usually more
informative, is far more challenging. The difficulty is largely due to
variability in mouse postures across frames. RESULTS: Here, we present OptiMouse,
an extensively documented open-source MATLAB program providing comprehensive
semiautomatic analysis of mouse position data. The emphasis in OptiMouse is
placed on minimizing errors in position detection. This is achieved by allowing
application of multiple detection algorithms to each video, including custom user
defined algorithms, by selection of the optimal algorithm for each frame, and by
correction when needed using interpolation or manual specification of positions.
CONCLUSIONS: At a basic level, OptiMouse is a simple and comprehensive solution
for analysis of position data. At an advanced level, it provides an open-source
and expandable environment for a detailed analysis of mouse position data.
PMID- 28506281
TI - A telephonic mindfulness-based intervention for persons with sickle cell disease:
study protocol for a randomized controlled trial.
AB - BACKGROUND: One of the most difficult symptoms for persons with sickle cell
disease (SCD) to manage is chronic pain. Chronic pain impacts approximately one
third of persons with SCD and is associated with increased pain intensity, pain
behavior, and frequency and duration of hospital visits. A promising category of
nonpharmacological interventions for managing both physical and affective
components of pain are mindfulness-based interventions (MBIs). METHODS/DESIGN:
The primary aim of this study is to conduct a randomized controlled study to
evaluate the acceptability and feasibility, as well as to determine the
preliminary efficacy, of a telephonic MBI for adults with SCD who have chronic
pain. We will enroll 60 adult patients with SCD and chronic pain at an outpatient
comprehensive SCD center in the southeastern United States. Patients will be
randomized to either an MBI or a wait-listed control group. The MBI group will
complete a six-session (60 minutes), telephonically delivered, group-based MBI
program. The feasibility, acceptability, and efficacy of the MBI regarding pain
catastrophizing will be assessed by administering questionnaires at baseline and
weeks 1, 3, and 6. In addition, ten randomly selected MBI participants will
complete semistructured interviews to help determine intervention acceptability.
DISCUSSION: In this study protocol, we report detailed methods of the randomized
controlled trial. Findings of this study will be useful to determine the
acceptability, feasibility, and efficacy of an MBI for persons with SCD and
chronic pain. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02394587 .
Registered on 9 February 2015.
PMID- 28506282
TI - Under-triage in telephone consultation is related to non-normative symptom
description and interpersonal communication: a mixed methods study.
AB - BACKGROUND: Telephone consultation and triage are used to limit the workload on
emergency departments. Lack of visual cues and clinical tests put telephone
consultations to a disadvantage compared to face-to-face consultations increasing
the risk of under-triage. Under-triage occurs in telephone triage; however why
under-triage happens is not explored yet. The aim of the study was to describe
situations of under-triage in context, to assess the quality of under-triaged
calls, and to identify communication patterns contributing to under-triage in a
regional OOH service in the capital region of Denmark. METHODS: Explanatory
simultaneous mixed method with thematic analysis and descriptive statistics was
chosen. The study was carried out in an Out-Of-Hours service (OOH) in the Capital
Region of Denmark, Copenhagen. Under-triage was defined as Potentially Under
Triaged Calls (PUTC) by specific criteria to an OOH Hotline, and identification
by integration of three databases: Medical Hotline database, Emergency number
database, including the Ambulance database, and electronic patient records.
Distribution of PUTC were carried out using ICD-10 codes to identify diagnosis
and main themes identified by qualitative analysis of audio recorded under
triaged calls. Study period was October 15th to November 30th 2014. RESULTS:
Three hundred twenty seven PUTC were identified, representing 0.04% of all calls
(n = 937.056) to the OOH. Distribution of PUTC according to diagnoses was:
digestive (24%), circulatory (19%), respiratory (15%) and all others (42%).
Thematic analysis of the voice logs suggested that inadequate communication and
non-normative symptom description contributed to under-triage. DISCUSSION: The
incidence of potentially under-triage is low (0.04%). However, the over
representation of digestive, circulatory, and respiratory diagnoses might suggest
that under-triage is related to inadequate symptom description. We recommend that
caller and call-handler collaborate systematically on problem identification and
negotiate non-normative symptom description. CONCLUSION: The incidence of under
triage is low (0.04%). However, the over-representation of digestive,
circulatory, and respiratory diagnoses might suggest that under-triage is related
to inadequate symptom description. We recommend that caller and call-handler
collaborate systematically on problem identification and negotiate non-normative
symptom description.
PMID- 28506285
TI - Centralised versus local measurement of glycated haemoglobin in clinical trial
settings: a comment on Arch et al., Trials. 2016.
AB - Arch and colleagues in their 24 October 2016 paper in Trials focus on the issue
of centralised versus local measurement of glycated haemoglobin (HbA1c) in
clinical trial settings. Resolution of the debate is important: while local HbA1c
measurement is less costly, and would thereby ease the stretched funding
situations for clinical trials worldwide, it cannot be implemented at the expense
of clinically unacceptable disparities between centralised and localised
measurements. Arch and colleagues favour centralised measurement in their paper's
conclusion. However, critical questions regarding the methods require a closer
look. In this letter, we discuss some of the issues that the authors could
clarify in order that the reader can agree (or disagree) to their inference with
greater confidence.
PMID- 28506283
TI - Prolactin blocks the expression of receptor activator of nuclear factor kappaB
ligand and reduces osteoclastogenesis and bone loss in murine inflammatory
arthritis.
AB - BACKGROUND: Prolactin (PRL) reduces joint inflammation, pannus formation, and
bone destruction in rats with polyarticular adjuvant-induced arthritis (AIA).
Here, we investigate the mechanism of PRL protection against bone loss in AIA and
in monoarticular AIA (MAIA). METHODS: Joint inflammation, trabecular bone loss,
and osteoclastogenesis were evaluated in rats with AIA treated with PRL (via
osmotic minipumps) and in mice with MAIA that were null (Prlr-/-) or not
(Prlr+/+) for the PRL receptor. To help define target cells, synovial fibroblasts
from Prlr+/+ mice were treated or not with proinflammatory cytokines ((Cyt),
including TNFalpha, IL-1beta, and interferon (IFN)gamma) with or without PRL, and
these synovial cells were co-cultured or not with bone marrow osteoclast
progenitors from Prlr+/+ or Prlr-/- mice. RESULTS: In AIA, PRL treatment reduced
joint swelling, increased trabecular bone area, lowered osteoclast density, and
reduced mRNA levels of osteoclast-associated genes (tartrate-resistant acid
phosphatase (Trap)), cathepsin K (Ctsk), matrix metalloproteinase 9 (Mmp9), and
receptor activator of nuclear factor kappaB or RANK (Tnfrsf11a)), of genes
encoding cytokines with osteoclastogenic activity (Tnfa, Il1b, Il6, and receptor
activator of nuclear factor kappaB ligand or RANKL (Tnfrsf11)), and of genes
encoding for transcription factors and cytokines related to T helper (Th)17 cells
(Rora, Rorc, Il17a, Il21, Il22) and to regulatory T cells (Foxp3, Ebi3, Il12a,
Tgfb1, Il10). Prlr-/- mice with MAIA showed enhanced joint swelling, reduced
trabecular bone area, increased osteoclast density, and elevated expression of
Tnfa, Il1b, Il6, Trap, Tnfrsf11a, Tnfrsf11, Il17a, Il21, Il22, 1 l23, Foxp3, and
Il10. The expression of the long PRL receptor form increased in arthritic joints,
and in synovial membranes and cultured synovial fibroblasts treated with Cyt. PRL
induced the phosphorylation/activation of signal transducer and activator of
transcription-3 (STAT3) and inhibited the Cyt-induced expression of Il1b, Il6,
and Tnfrsf11 in synovial fibroblast cultures. The STAT3 inhibitor S31-201 blocked
inhibition of Tnfrsf11 by PRL. Finally, PRL acted on both synovial fibroblasts
and osteoclast precursor cells to downregulate Cyt-induced osteoclast
differentiation. CONCLUSION: PRL protects against osteoclastogenesis and bone
loss in inflammatory arthritis by inhibiting cytokine-induced expression of RANKL
in joints and synovial fibroblasts via its canonical STAT3 signaling pathway.
PMID- 28506284
TI - The INVEST project: investigating the use of evidence synthesis in the design and
analysis of clinical trials.
AB - BACKGROUND: When designing and analysing clinical trials, using previous relevant
information, perhaps in the form of evidence syntheses, can reduce research
waste. We conducted the INVEST (INVestigating the use of Evidence Synthesis in
the design and analysis of clinical Trials) survey to summarise the current use
of evidence synthesis in trial design and analysis, to capture opinions of
trialists and methodologists on such use, and to understand any barriers.
METHODS: Our sampling frame was all delegates attending the International
Clinical Trials Methodology Conference in November 2015. Respondents were asked
to indicate (1) their views on the use of evidence synthesis in trial design and
analysis, (2) their own use during the past 10 years and (3) the three greatest
barriers to use in practice. RESULTS: Of approximately 638 attendees of the
conference, 106 (17%) completed the survey, half of whom were statisticians.
Support was generally high for using a description of previous evidence, a
systematic review or a meta-analysis in trial design. Generally, respondents did
not seem to be using evidence syntheses as often as they felt they should. For
example, only 50% (42/84 relevant respondents) had used a meta-analysis to inform
whether a trial is needed compared with 74% (62/84) indicating that this is
desirable. Only 6% (5/81 relevant respondents) had used a value of information
analysis to inform sample size calculations versus 22% (18/81) indicating support
for this. Surprisingly large numbers of participants indicated support for, and
previous use of, evidence syntheses in trial analysis. For example, 79% (79/100)
of respondents indicated that external information about the treatment effect
should be used to inform aspects of the analysis. The greatest perceived barrier
to using evidence synthesis methods in trial design or analysis was time
constraints, followed by a belief that the new trial was the first in the area.
CONCLUSIONS: Evidence syntheses can be resource-intensive, but their use in
informing the design, conduct and analysis of clinical trials is widely
considered desirable. We advocate additional research, training and investment in
resources dedicated to ways in which evidence syntheses can be undertaken more
efficiently, offering the potential for cost savings in the long term.
PMID- 28506286
TI - High protein intake without concerns?
AB - The high fashion in nutrition for the critically ill is to recommend a high
protein intake. Several opinion leaders are surfing on this wave, expanding the
suggested protein allowance upwards. At the same time, there is no new evidence
supporting this change in recommendations. Observational data show that in
clinical practice protein intake is most often far below current ESPEN
recommendations of 1.2-1.5 g/kg/day. Therefore, it may be in the best interests
of our patients just to adhere to that guideline, and not to stretch them upwards
for protein intake? Here we give arguments to stay conservative.
PMID- 28506287
TI - Long-term outcomes of 307 patients after complete thymoma resection.
AB - BACKGROUND: Thymoma is an uncommon tumor without a widely accepted standard care
to date. We aimed to investigate the clinicopathologic variables of patients with
thymoma and identify possible predictors of survival and recurrence after initial
resection. METHODS: We retrospectively selected 307 patients with thymoma who
underwent complete resection at the Cancer Hospital, Chinese Academy of Medical
Sciences and Peking Union Medical College (Beijing, China) between January 2003
and December 2014. The associations of patients' clinical characteristics with
prognosis were estimated using Cox regression and Kaplan-Meier survival analyses.
RESULTS: During follow-up (median, 86 months; range, 24-160 months), the 5- and
10-year disease-free survival (DFS) rates were 84.0% and 73.0%, respectively, and
the 5- and 10-year overall survival (OS) rates were 91.0% and 74.0%,
respectively. Masaoka stage (P < 0.001), World Health Organization (WHO)
histological classification (P < 0.001), and postoperative radiotherapy after
initial resection (P = 0.006) were associated with recurrence (52/307, 16.9%).
Multivariate analysis revealed that, after initial resection, WHO histological
classification and Masaoka stage were independent predictors of DFS and OS. The
pleura (25/52, 48.0%) were the most common site of recurrence, and locoregional
recurrence (41/52, 79.0%) was the most common recurrence pattern. The recurrence
pattern was an independent predictor of post-recurrence survival. Patients with
recurrent thymoma who underwent repeated resection had increased post-recurrence
survival rates compared with those who underwent therapies other than surgery (P
= 0.017). CONCLUSIONS: Masaoka stage and WHO histological classification were
independent prognostic factors of thymoma after initial complete resection. The
recurrence pattern was an independent predictor of post-recurrence survival.
Locoregional recurrence and repeated resection of the recurrent tumor were
associated with favorable prognosis.
PMID- 28506288
TI - Visualizing statistical significance of disease clusters using cartograms.
AB - BACKGROUND: Health officials and epidemiological researchers often use maps of
disease rates to identify potential disease clusters. Because these maps
exaggerate the prominence of low-density districts and hide potential clusters in
urban (high-density) areas, many researchers have used density-equalizing maps
(cartograms) as a basis for epidemiological mapping. However, we do not have
existing guidelines for visual assessment of statistical uncertainty. To address
this shortcoming, we develop techniques for visual determination of statistical
significance of clusters spanning one or more districts on a cartogram. We
developed the techniques within a geovisual analytics framework that does not
rely on automated significance testing, and can therefore facilitate visual
analysis to detect clusters that automated techniques might miss. RESULTS: On a
cartogram of the at-risk population, the statistical significance of a disease
cluster is determinate from the rate, area and shape of the cluster under
standard hypothesis testing scenarios. We develop formulae to determine, for a
given rate, the area required for statistical significance of a priori and a
posteriori designated regions under certain test assumptions. Uniquely, our
approach enables dynamic inference of aggregate regions formed by combining
individual districts. The method is implemented in interactive tools that provide
choropleth mapping, automated legend construction and dynamic search tools to
facilitate cluster detection and assessment of the validity of tested
assumptions. A case study of leukemia incidence analysis in California
demonstrates the ability to visually distinguish between statistically
significant and insignificant regions. CONCLUSION: The proposed geovisual
analytics approach enables intuitive visual assessment of statistical
significance of arbitrarily defined regions on a cartogram. Our research prompts
a broader discussion of the role of geovisual exploratory analyses in disease
mapping and the appropriate framework for visually assessing the statistical
significance of spatial clusters.
PMID- 28506289
TI - A preliminary investigation to explore the cognitive resources of physicians
experiencing difficulty in training.
AB - BACKGROUND: Treating patients is complex, and research shows that there are
differences in cognitive resources between physicians who experience
difficulties, and those who do not. It is possible that differences in some
cognitive resources could explain the difficulties faced by some physicians. In
this study, we explore differences in cognitive resources between different
groups of physicians (that is, between native (UK) physicians and International
Medical Graduates (IMG); those who continue with training versus those who were
subsequently removed from the training programme); and also between physicians
experiencing difficulties compared with the general population. METHODS: A
secondary evaluation was conducted on an anonymised dataset provided by the East
Midlands Professional Support Unit (PSU). One hundred and twenty one postgraduate
trainee physicians took part in an Educational Psychology assessment through PSU.
Referrals to the PSU were mainly on the basis of problems with exam progression
and difficulties in communication skills, organisation and confidence. Cognitive
resources were assessed using the Wechsler Adult Intelligence Scale (WAIS-IV).
Physicians were categorised into three PSU outcomes: 'Continued in training',
'Removed from training' and 'Active' (currently accessing the PSU). RESULTS:
Using a one-sample Z test, we compared the referred physician sample to a UK
general population sample on the WAIS-IV and found the referred sample
significantly higher in Verbal Comprehension (VCI; z = 8.78) and significantly
lower in Working Memory (WMI; z = -4.59). In addition, the native sample were
significantly higher in Verbal Comprehension than the UK general population
sample (VCI; native physicians: z = 9.95, p < .001, d = 1.25), whilst there was a
lesser effect for the difference between the IMG sample and the UK general
population (z = 2.13, p = .03, d = 0.29). Findings also showed a significant
difference in VCI scores between those physicians who were 'Removed from
training' and those who 'Continued in training'. CONCLUSIONS: Our results suggest
it is important to understand the cognitive resources of physicians to provide a
more focussed explanation of those who experience difficulties in training. This
will help to implement more targeted interventions to help physicians develop
compensatory strategies.
PMID- 28506290
TI - Pre-admission functional status impacts the performance of the APACHE IV model of
mortality prediction in critically ill patients.
AB - BACKGROUND: Functional status (FS) before intensive care unit (ICU) admission is
associated with short-term and long-term outcomes among critically ill patients.
However, measures of FS are generally not integrated into ICU-specific mortality
prediction models. METHODS: This retrospective cohort study used prospectively
collected data from 9638 consecutive patients admitted to a single ICU between 1
October 2005 and 30 September 2015. For each ICU admission, FS was prospectively
determined and classified into three discrete categories based on performance of
basic daily living activities (FS1 - fully independent; FS2 - partly dependent;
FS3 - completely dependent). We prospectively calculated Acute Physiology and
Chronic Health Evaluation (APACHE) IV predicted mortality percentage (APIV PM)
for each admission and calculated observed-expected mortality ratios (OEMR),
stratified by FS category and APIV PM. We calculated area under the receiver
operator characteristic curve (AUC) for APIV PM and mortality for the entire
cohort and the three FS categories. RESULTS: Patients had a median (IQR) age of
67 (52-80) years and mean (SD) APIV PM was 18.3% (24.3%). Of these, 7714 (80.0%)
were classified as FS1, 1728 (17.9%) as FS2 and 196 (2.0%) as FS3. FS1 patients
were younger, had less comorbid disease, and lower APIV PM compared to FS2 and
FS3. The OEMR were significantly lower for FS1 (0.67) than FS2 (0.93) or FS3
(0.90) (p < 0.0001 for both comparisons). Among patients with APIV PM 0-10%, 10
25%, 25-50% and >=50% the OEMR for FS1 were 0.33, 0.49, 0.61 and 0.86. The AUC
(95% CI) for APIV PM and mortality for FS1, FS2 and FS3 were 0.924 (0.914-0.933),
0.837 (0.816-0.858) and 0.775 (0.705-0.8456), respectively (p < 0.001 for each
comparison). Multivariable analysis demonstrated that FS2 (OR 2.18 (1.84-2.57) (p
< 0.0001)) and FS3 (OR 1.99 (1.34-2.96) (p = 0.0006)) were independently
associated with increased risk of mortality. CONCLUSIONS: Baseline FS prior to
critical illness is a strong independent predictor of mortality and impacts the
relationship between observed and APIV PM in those with lower illness severity.
Future iterations of mortality prediction models should integrate a baseline
measure of FS to improve performance.
PMID- 28506292
TI - Normobaric hypoxia overnight impairs cognitive reaction time.
AB - BACKGROUND: Impaired reaction time in patients suffering from hypoxia during
sleep, caused by sleep breathing disorders, is a well-described phenomenon. High
altitude sleep is known to induce periodic breathing with central apneas and
oxygen desaturations, even in perfectly healthy subjects. However, deficits in
reaction time in mountaineers or workers after just some nights of hypoxia
exposure are not sufficiently explored. Therefore, we aimed to investigate the
impact of sleep in a normobaric hypoxic environment on reaction time divided by
its cognitive and motoric components. Eleven healthy non acclimatized students
(5f, 6m, 21 +/- 2.1 years) slept one night at a simulated altitude of 3500 m in a
normobaric hypoxic room, followed by a night with polysomnography at simulated
5500 m. Preexisting sleep disorders were excluded via BERLIN questionnaire. All
subjects performed a choice reaction test (SCHUHFRIED RT, S3) at 450 m and
directly after the nights at simulated 3500 and 5500 m. RESULTS: We found a
significant increase of cognitive reaction time with higher altitude (p = 0.026).
No changes were detected in movement time (p = n.s.). Reaction time, the combined
parameter of cognitive- and motoric reaction time, didn't change either (p =
n.s.). Lower SpO2 surprisingly correlated significantly with shorter cognitive
reaction time (r = 0.78, p = 0.004). Sleep stage distribution and arousals at
5500 m didn't correlate with reaction time, cognitive reaction time or movement
time. CONCLUSION: Sleep in hypoxia does not seem to affect reaction time to
simple tasks. The component of cognitive reaction time is increasingly delayed
whereas motoric reaction time seems not to be affected. Low SpO2 and arousals are
not related to increased cognitive reaction time therefore the causality remains
unclear. The fact of increased cognitive reaction time after sleep in hypoxia,
considering high altitude workers and mountaineering operations with overnight
stays, should be further investigated.
PMID- 28506291
TI - Targeting CD22 with the monoclonal antibody epratuzumab modulates human B-cell
maturation and cytokine production in response to Toll-like receptor 7 (TLR7) and
B-cell receptor (BCR) signaling.
AB - BACKGROUND: Abnormal B-cell activation is implicated in the pathogenesis of
autoimmune diseases, including systemic lupus erythematosus (SLE). The B-cell
surface molecule CD22, which regulates activation through the B-cell receptor
(BCR), is a potential target for inhibiting pathogenic B cells; however, the
regulatory functions of CD22 remain poorly understood. In this study, we
determined how targeting of CD22 with epratuzumab (Emab), a humanized anti-CD22
IgG1 monoclonal antibody, affects the activation of human B-cell subsets in
response to Toll-like receptor 7 (TLR7) and BCR engagement. METHODS: B-cell
subsets were isolated from human tonsils and stimulated with F(ab')2 anti-human
IgM and/or the TLR7 agonist R848 in the presence of Emab or a human IgG1 isotype
control. Changes in mRNA levels of genes associated with B-cell activation and
differentiation were analyzed by quantitative PCR. Cytokine production was
measured by ELISA. Cell proliferation, survival, and differentiation were
assessed by flow cytometry. RESULTS: Pretreatment of phenotypically naive
CD19+CD10-CD27- cells with Emab led to a significant increase in IL-10
expression, and in some but not all patient samples to a reduction of IL-6
production in response to TLR7 stimulation alone or in combination with anti-IgM.
Emab selectively inhibited the expression of PRDM1, the gene encoding B
lymphocyte-induced maturation protein 1 (Blimp-1) in activated CD10-CD27- B
cells. CD10-CD27-IgD- cells were highly responsive to stimulation through TLR7 as
evidenced by the appearance of blasting CD27hiCD38hi cells. Emab significantly
inhibited the activation and differentiation of CD10-CD27-IgD- B cells into
plasma cells. CONCLUSIONS: Emab can both regulate cytokine expression and block
Blimp1-dependent B-cell differentiation, although the effects of Emab may depend
on the stage of B-cell development or activation. In addition, Emab inhibits the
activation of CD27-IgD- tonsillar cells, which correspond to so-called double
negative memory B cells, known to be increased in SLE patients with more active
disease. These data may be relevant to the therapeutic effect of Emab in vivo via
modulation of the production of pro-inflammatory and anti-inflammatory cytokines
by B cells. Because Blimp-1 is required by B cells to mature into antibody
producing cells, inhibition of Blimp1 may reduce autoantibody production.
PMID- 28506293
TI - Case report of unexpected gastrointestinal involvement in type 1 Gaucher disease:
comparison of eliglustat tartrate treatment and enzyme replacement therapy.
AB - BACKGROUND: Gastrointestinal involvement in Gaucher disease is very rare, and
appears to be unresponsive to enzyme replacement therapy (ERT). CASE
PRESENTATION: Here, we describe identical twin, splenectomized, non-neuronopathic
Gaucher patients on long-term ERT for 9 years, who complained of epigastric
discomfort due to Gaucher cell infiltration of the gastroduodenal mucosa. Rare
compound heterozygous mutations (p.Arg48Trp and p.Arg257Gln) of the GBA gene were
found in both. Improvement in the gastroduodenal infiltration and reduced
chitotriosidase levels were observed in one who switched to eliglustat tartrate
for 1 year, whereas the other one who maintained ERT showed no improvement of
chitotriosidase level and persistent duodenal lesions. CONCLUSION: This shows
that eliglustat might be an effective treatment for Gaucher disease patients
having lesions resistant to ERT.
PMID- 28506294
TI - hSSB1 associates with and promotes stability of the BLM helicase.
AB - BACKGROUND: Maintenance of genome stability is critical in human cells. Mutations
in or loss of genome stability pathways can lead to a number of pathologies
including cancer. hSSB1 is a critical DNA repair protein functioning in the
repair and signalling of stalled DNA replication forks, double strand DNA breaks
and oxidised DNA lesions. The BLM helicase is central to the repair of both
collapsed DNA replication forks and double strand DNA breaks by homologous
recombination. RESULTS: In this study, we demonstrate that hSSB1 and BLM helicase
form a complex in cells and the interaction is altered in response to ionising
radiation (IR). BLM and hSSB1 also co-localised at nuclear foci following IR
induced double strand breaks and stalled replication forks. We show that hSSB1
depleted cells contain less BLM protein and that this deficiency is due to
proteasome mediated degradation of BLM. Consequently, there is a defect in
recruitment of BLM to chromatin in response to ionising radiation-induced DSBs
and to hydroxyurea-induced stalled and collapsed replication forks. CONCLUSIONS:
Our data highlights that BLM helicase and hSSB1 function in a dynamic complex in
cells and that this complex is likely required for BLM protein stability and
function.
PMID- 28506295
TI - Gender-specific predictors of at-risk adolescents' hazardous alcohol use-a cohort
study.
AB - BACKGROUND: Previous research has found strong associations between adolescents'
hazardous alcohol use and their perception of peer behavior, as well as own
spending money and a range of antisocial behaviors. However, there is
insufficient evidence of gender-specific predictors among adolescents with
elevated antisocial behavior and alcohol use to design effective selective
interventions. The aims of this study were to test short-term predictors of Heavy
Episodic Drinking (HED) and risk-use of alcohol among 12-18-year-old females and
males with elevated externalizing and delinquent behavior, and alcohol use.
METHODS: Eighty-five females, 77 males, and their parents, originally recruited
for a parent intervention, were assessed at baseline and 6 months later with
several validated instruments measuring externalizing and internalizing behavior,
alcohol use, psychosocial distress, and delinquency. RESULTS: The perception of
peer drinking significantly predicted both genders' HED and risk-use, and also
externalizing behavior predicted female risk-use. Rule-breaking behavior and
social problems predicted both HED and risk-use among males, while rule-breaking
predicted female HED and social problems predicted female risk-use. The parents'
ratings of externalizing behavior predicted only their sons' risk-use. Lastly, no
differences in prediction strength were found to be statistically significant
differences between genders. CONCLUSIONS: Females and males shared several
predictors of hazardous alcohol use, and perception of peer drinking emerged as a
strong predictor. This suggests that interventions may target both genders'
hazardous use of alcohol, and should address peer-resisting skills.
PMID- 28506296
TI - Worlds apart? A scoping review addressing different stakeholder perspectives on
barriers to family involvement in the care for persons with severe mental
illness.
AB - BACKGROUND: Empirical evidence shows that family involvement (FI) can play a
pivotal role in the coping and recovery of persons with severe mental illness
(SMI). Nevertheless, various studies demonstrate that FI in mental healthcare
services is often not (sufficiently) realized. In order to develop more insights,
this scoping review gives an overview of how various stakeholders conceptualize,
perceive and experience barriers to FI. Central questions are: 1) What are the
main barriers to FI reported by the different key stakeholders (i.e. the persons
with SMI, their families and the professionals, and 2) What are the differences
and similarities between the various stakeholders' perspectives on these
barriers. METHODS: A systematic search into primary studies regarding FI was
conducted in four databases: Medline/Pubmed, Cinahl, PsychInfo and Web of
Knowledge with the use of a PICO scheme. Thematic analysis focused on stakeholder
perspectives (i.e. which stakeholder group reports the barrier) and types of
barriers (i.e. which types of barriers are addressed). RESULTS: Thirty three
studies were included. The main barriers reported by the stakeholder groups
reveal important similarities and differences between the stakeholder groups and
were related to: 1) the person with SMI, 2) the family, 3) the professionals, 4)
the organization of care and 5) the culture-paradigm. DISCUSSION: Our stakeholder
approach elicits the different stakeholders' concepts, presuppositions and
experiences of barriers to FI, and gives fundamental insights on how to deal with
barriers to FI. The stakeholders differing interpretations and perceptions of the
barriers related to FI is closely related to the inherent complexity involved in
FI in itself. In order to deal better with these barriers, openly discussing and
reflecting upon each other's normative understandings of barriers is needed.
CONCLUSIONS: Differences in perceptions of barriers to FI can itself be a
barrier. To deal with barriers to FI, a dialogical approach on how the different
stakeholders perceive and value FI and its barriers is required. Methods such as
moral case deliberation or systematic ethics reflections can be useful.
PMID- 28506297
TI - Cervical cancer treatment costs and cost-effectiveness analysis of human
papillomavirus vaccination in Vietnam: a PRIME modeling study.
AB - BACKGROUND: Cervical cancer is currently the leading cause of cancer mortality
among women in South Vietnam and the second leading cause of cancer mortality in
North Vietnam. Human papillomavirus (HPV) vaccination has the potential to
substantially decrease this burden. The World Health Organization (WHO)
recommends that a cost-effectiveness analysis of HPV vaccination is conducted
before nationwide introduction. METHODS: The Papillomavirus Rapid Interface for
Modeling and Economics (PRIME) model was used to evaluate the cost-effectiveness
of HPV vaccine introduction. A costing study based on expert panel discussions,
interviews and hospital case note reviews was conducted to explore the cost of
cervical cancer care. RESULTS: The cost of cervical cancer treatment ranged from
US$368 - 11400 depending on the type of hospital and treatment involved. Under
Gavi-negotiated prices of US$4.55, HPV vaccination is likely to be very cost
effective with an incremental cost per disability-adjusted life year (DALY)
averted in the range US$780 - 1120. However, under list prices for Cervarix and
Gardasil in Vietnam, the incremental cost per DALY averted for HPV vaccination
can exceed US$8000. CONCLUSION: HPV vaccine introduction appears to be
economically attractive only if Vietnam is able to procure the vaccine at Gavi
prices. This highlights the importance of initiating a nationwide vaccination
programme while such prices are still available.
PMID- 28506298
TI - FecX Bar a Novel BMP15 mutation responsible for prolificacy and female sterility
in Tunisian Barbarine Sheep.
AB - BACKGROUND: Naturally occurring mutations in growth and differentiation factor 9
(GDF9) or bone morphogenetic protein 15 (BMP15) genes are associated with
increased ovulation rate (OR) and litter size (LS) but also sterility. Observing
the Tunisian Barbarine ewes of the "W" flock selected for improved prolificacy,
we found prolific and infertile ewes with streaky ovaries. Blood genomic DNA was
extracted from a subset of low-ovulating, prolific and infertile ewes of the "W"
flock, and the entire coding sequences of GDF9 and BMP15 were sequenced. RESULTS:
We evidenced a novel polymorphism in the exon 1 of the BMP15 gene associated with
increased prolificacy and sterility. This novel mutation called FecX Bar is a
composite polymorphism associating a single nucleotide substitution (c.301G > T),
a 3 bp deletion (c.302_304delCTA) and a C insertion (c.310insC) in the ovine
BMP15 cDNA leading to a frame shift at protein position 101. Calculated in the
"W" flock, the FecX Bar allele increased OR by 0.7 ova and LS by 0.3 lambs (p =
0.08). As for already identified mutations, homozygous females carrying FecX Bar
exhibited streaky ovaries with a blockade at the primary stage of
folliculogenesis as shown by histochemistry. CONCLUSIONS: Our investigation
demonstrates a new mutation in the BMP15 gene providing a valuable genetic tool
to control fecundity in Tunisian Barbarine, usable for diffusion program into
conventional flocks looking for prolificacy improvement.
PMID- 28506299
TI - Developmental hip dysplasia treated by total hip arthroplasty using a cementless
Wagner cone stem in young adult patients with a small physique.
AB - BACKGROUND: Developmental hip dysplasia (DDH) may lead to severe acetabular and
femoral abnormalities that can render total hip arthroplasty (THA) challenging,
especially in DDH patients with a small physique. Most conventional cemented or
cementless femoral components are often difficult to implant in the narrow
femoral canal and require slight version correction during surgery. The aim of
this study was to present the mid-term results of THA in the treatment of DDH
patients with a small physique using a cementless Wagner cone prosthesis
(Zimmer(r), US). METHODS: Between January 2006 and March 2010, we retrospectively
reviewed 50 patients who were treated at our center. A total of 50 patients (52
hips; 45 women, five men; mean age 32.5 years; range 27 to 38 years) who
underwent THA were observed. The mean femoral medullary canal dimension at the
isthmus was 7.6 mm (range 6.0 to 8.7). According to the Crowe classification, 19
hips presented dysplasia of grade I, while 33 presented dysplasia of grade II.
All patients were treated with THA using a cementless Wagner cone prosthesis.
Clinical and radiologic evaluations were performed on all patients. RESULTS: The
mean duration of follow-up was 7.7 years (range 5.4 to 10.5). The Harris hip
score (HHS) improved from 63 +/- 9 (range 55 to 70) pre-operatively to 92 +/- 8
(range 88 to 100) at the last follow-up. The HHS at the most recent follow-up was
excellent in 66% of patients (34 hips), good in 26% (14 hips), fair in 6% (3
hips), and poor in 2% (1 hip). Radiographic evaluation demonstrated excellent
osteointegration of the implants. Stem subsidence was present in three stems, and
the range of stem subsidence was 2 mm in two stems (3.9%) and 3 mm in one stem
(1.9%). Femoral osteolysis was observed in nine hips (18%) in the proximal zones,
and no distal osteolysis was noted. Heterotopic ossification was observed in
three hips (5.8%); of these, two were classified as Brooker's grade 1, and one
was classified as Brooker's grade 2 at the most recent follow-up. None of the
implants were revised. CONCLUSIONS: Based on the tapered shape and free setting
of anteversion, the Wagner cone femoral stem facilitates its implantation in
dysplastic hips. Therefore, this series of short stems with a smaller diameter
can ensure safe implantation in narrow medullary canals, especially in young DDH
patients with a small physique. TRIAL REGISTRATION: Registration Number: ChiCTR
ORC-17011181 . Reg Date: 2017-04-19 00:44:59 Retrospective registration.
PMID- 28506301
TI - Diffuse non-midline glioma with H3F3A K27M mutation: a prognostic and treatment
dilemma.
PMID- 28506300
TI - Cross-cultural adaptation and psychometric analysis of the Arabic version of the
oxford knee score in adult male with knee osteoarthritis.
AB - BACKGROUND: There are varieties of self-assessment questionnaire used for the
evaluation of pain, functional disability, and health related quality of life in
individuals with knee osteoarthritis (OA). The present study intended to adapt
and translate the oxford knee score into the Arabic and investigated its
psychometric properties in adult male with knee OA. METHODS: Ninety-seven adult
male (mean age 57.55 +/- 11.49 years) with knee OA participated. Patients were
requested to complete the adapted Arabic version of the Oxford knee score (OKS
Ar), reduced "Western Ontario and McMaster Universities Index (WOMAC)", and the
Visual analogue scale (VAS). Patients were requested to complete 2nd form of OKS
Ar at least 1 week apart to assess the reproducibility of the score. The OKS was
adapted and translated into Arabic by two independent Arabic native speakers (one
rehabilitation professional having experience of knee OA patients and another one
a trained translator) according to the international guidelines. RESULTS: All the
participants completed the 2nd form of OKS-Ar (Response rate 100%). Reliability
and internal consistency was high with an ICC of 0.97, and the Cronbach's alpha
coefficient of 0.987, respectively. A significant relationship between the OKS-Ar
and the WOMAC and VAS scores confirmed the construct validity (p < 0.001). The
standard error of measurement (SEM) and the minimum detectable change (MDC) were
2.2 and 6.2, respectively. CONCLUSIONS: The adapted Arabic version of the OKS
demonstrated acceptable psychometric properties, including reliability, internal
consistency, and the validity. The present study indicates that the OKS-Ar is a
suitable questionnaire to measure pain and physical function in the Arabic
speaking adult male patients with knee OA.
PMID- 28506303
TI - Erratum to: Contribution of Candida biomarkers and DNA detection for the
diagnosis of invasive candidiasis in ICU patients with severe abdominal
conditions.
PMID- 28506302
TI - Quantification of gait in mitochondrial m.3243A > G patients: a validation study.
AB - BACKGROUND: More than half of the patients harbouring the m.3243A > G mutation
were found to have trouble maintaining balance when walking in a recent study by
our group. Others demonstrated that these patients had an abnormal gait pattern,
as quantified by gait analysis. Gait analysis is an emerging method to quantify
subtle changes in walking pattern, also during therapeutic interventions.
Therefore, we aimed to test the reliability and reproducibility of gait analysis
and select the most suitable protocol for this group of patients using a GAITRite
electronic walkway. Four different protocols were tested: normal walking, dual
task, post exercise and after a ten minutes of rest. RESULTS: In total 36
patients with the m.3243A > G mutation and 50 healthy controls were enrolled in
this study. Overall high intra class correlation coefficients were found in all
experimental conditions for both patients and healthy controls indicating good
reproducibility. Marked differences in gait between patients and controls were
observed and were in line with the only available exploratory study performed.
There was a good correlation between both the overall NMDAS score, NMDAS subscale
scores, both markers for disease severity, and specific gait parameters.
CONCLUSIONS: The observed reliability of the test makes GAITRite a suitable
instrument for intervention studies in patients with mitochondrial disease.
PMID- 28506304
TI - Characterization of genetic aberrations in a single case of metastatic thymic
adenocarcinoma.
AB - BACKGROUND: Thymic adenocarcinoma is an extremely rare subtype of thymic
epithelial tumors. Due to its rarity, there is currently no sequencing approach
for thymic adenocarcinoma. METHODS: We performed whole exome and transcriptome
sequencing on a case of thymic adenocarcinoma and performed subsequent validation
using Sanger sequencing. RESULTS: The case of thymic adenocarcinoma showed
aggressive behaviors with systemic bone metastases. We identified a high
incidence of genetic aberrations, which included somatic mutations in RNASEL,
PEG10, TNFSF15, TP53, TGFB2, and FAT1. Copy number analysis revealed a complex
chromosomal rearrangement of chromosome 8, which resulted in gene fusion between
MCM4 and SNTB1 and dramatic amplification of MYC and NDRG1. Focal deletion was
detected at human leukocyte antigen (HLA) class II alleles, which was previously
observed in thymic epithelial tumors. We further investigated fusion transcripts
using RNA-seq data and found an intergenic splicing event between the CTBS and
GNG5 transcript. Finally, enrichment analysis using all the variants represented
the immune system dysfunction in thymic adenocarcinoma. CONCLUSION: Thymic
adenocarcinoma shows highly malignant characteristics with alterations in several
cancer-related genes.
PMID- 28506305
TI - Effect of chemotherapy counseling by pharmacists on quality of life and
psychological outcomes of oncology patients in Malaysia: a randomized control
trial.
AB - BACKGROUND: Cancer is now becoming a leading cause of death. Chemotherapy is an
important treatment for cancer patients. These patients also need consultation
during their treatment to improve quality of life and decrease psychological
disorders. The objectives of the study were to develop, implement and evaluate
the effectiveness of a chemotherapy counseling module by pharmacists among
oncology patients on their quality of life and psychological outcomes in
Malaysia. METHOD: A single-blind randomized controlled trial was carried out
among 162 oncology patients undergoing chemotherapy from July 2013 to February
2014 in a government hospital with oncology facilities in Malaysia. Participants
were randomized to either the intervention group or the control group.
Chemotherapy counseling using the module on 'Managing Patients on Chemotherapy'
by Pharmacists was delivered to the intervention group. The outcome measures were
assessed at baseline, first follow-up and second follow-up and third follow-up
post-intervention. Chi-square, independent samples t-test and two-way repeated
measures ANOVA were conducted in the course of the data analyses. RESULTS: In
assessing the impact of the chemotherapy counseling module, the study revealed
that the module along with repetitive counseling showed significant improvement
of quality of life in the intervention group as compared to the control group
with a large effect size in physical health (p = 0.001, partial N2 = 0.66),
psychological (p = 0.001, partial N2 = 0.65), social relationships (p = 0.001,
partial N2 = 0.30), and environment (p = 0.001, partial N2 = 0.67) and decrease
in the anxiety (p = 0.000; partial N2 = 0.23), depression (p = 0.000; partial N2
= 0.40). CONCLUSION: The module on 'Managing Patients on Chemotherapy' along with
repetitive counseling by pharmacists has been shown to be effective in improving
quality of life and decreasing anxiety and depression among oncology patients
undergoing chemotherapy. TRIAL REGISTRATION NUMBER: National Medical Research
Register (NMRR) of Malaysia and given a registration number NMRR-12-1057-12,363
on 21 December 2012.
PMID- 28506306
TI - Predictors of physical and mental health in persons with morbid obesity attending
a patient education course - a two-year follow-up study.
AB - BACKGROUND: People with morbid obesity (body mass index >=40) may experience
changes in their health after participating in a tailored patient education
course. The aims of this study were to assess the changes in physical and mental
health in persons with morbid obesity during the 2 years following an educational
course and to explore possible socio-demographic, treatment, and personal
predictors of physical and mental health outcomes. METHODS: In this prospective
longitudinal cohort study, self-report questionnaire data were collected from
people with morbid obesity at the beginning of mandatory educational courses
while on a waiting list for gastric surgery and at two-year follow-up. Of the 185
who attended the courses, 142 (77%) volunteered to participate in the study, and
the 59 with complete data at the two-year follow-up were included in the
analysis. Physical and mental health were measured with the physical and mental
component summary scores from the Short Form 12v2. Self-esteem was measured by
the Rosenberg Self-Esteem Scale, and self-efficacy by the General Self-Efficacy
Scale. RESULTS: The participants reported better physical health at two-year
follow-up than at baseline. Mental health did not change significantly over time.
Receiving surgical treatment during the study period predicted better physical
health at two-year follow-up, even after controlling for physical health at
baseline. Mental health at baseline was the only significant baseline predictor
of mental health at follow-up. However, increasing self-esteem and self-efficacy
over the two-year study period independently predicted better mental health at
follow up after controlling for mental health at baseline. CONCLUSION: Our study
showed that people with morbid obesity on a waiting list for bariatric surgery
improved their physical health during the 2 years after attending a tailored
patient educational course. Improving self-esteem and self-efficacy may be
important personal factors for maintaining mental health during this period.
TRIAL REGISTRATION: NCT01336725 . Registered 14 April 2011.
PMID- 28506307
TI - Intestinal parasitic infections and its association with undernutrition and CD4 T
cell levels among HIV/AIDS patients on HAART in Butajira, Ethiopia.
AB - BACKGROUND: Intestinal parasitic infections and HIV/AIDS have been the major
public health problems and remain a vital cause of morbidity and mortality in
developing countries. Both problems are linked in a vicious cycle. The magnitude
of intestinal parasites was prevalent among people living with HIV/AIDS even in
the HAART era. However, the pertinent risk factors associated with intestinal
parasites among HIV/AIDS patients were not well investigated in Ethiopia
particularly at Butajira town. Therefore, the aim of this study was to determine
the prevalence of intestinal parasites and associated risk factors among HIV/AIDS
patients on HAART in Butajira, Ethiopia. METHOD: A cross-sectional study was
conducted, and a total of 323 study subjects was involved in the study. A
systematic random sampling technique was used to select each participant during
data collection. Stool specimen was collected and processed using direct wet
mount, formol-ether concentration technique, and modified Ziehl-Neelson staining
techniques to identify both common and opportunistic intestinal parasites.
Structured questionnaire was used to collect socio-demographic, environmental,
clinical, and nutritional data. Both bivariate and multivariate logistic
regression analyses were used to assess the association of various explanatory
factors on intestinal parasites. P value <=0.05 at 95% CI was considered
statistically significant. RESULTS: The overall prevalence of intestinal
parasites was 35.9% (95% CI 31.0-40.9%). Protozoa's (Entanmoeba
histolytica/dispar trophozoite, E. histolytica/dispar cyst, Giardia lamblia
trophozoite, and G. lamblia cyst), helminths (Tanea species, Ascaris
lumbricoides, Strongyloid stercoralis, Hookworm species and H. nana), and
opportunistic intestinal parasites (Cryptosporidium parvum, Isospora belli) were
observed in 57 (17.1%), 46 (14.4%), and 28 (8.7%) study participants
respectively. Multivariate logistic regression analysis revealed that the
presence of animals (AOR 6. 14; 95% CI 3.13, 12.0); using river water (AOR 4.87;
95% CI 1.14, 20.7); undernutrition (AOR 2.59; 95% CI 1.36-4.95); and level of
immunosuppression (AOR 4.02; 95% CI 1.78-9.05 and AOR 2.84; 95% CI 1.37-5.89)
were significantly associated with intestinal parasites. CONCLUSIONS: The
prevalence of intestinal parasites found to be higher among HIV/AIDS patients
receiving HAART at Butajira Hospital, southern Ethiopia. Presence of animals,
using river water, lower CD4 T cell count, and undernutrition were significant
factors affecting intestinal parasites. Therefore, consistent detection of
intestinal parasites and deworming of patients should be performed as well as
improving health education on personal hygiene, avoiding contact with pit or
domestic animals, and using safe or treated water. Furthermore, improving
nutritional support and household food access are recommended.
PMID- 28506308
TI - Attenuating immune pathology using a microbial-based intervention in a mouse
model of cigarette smoke-induced lung inflammation.
AB - BACKGROUND: Cigarette smoke exposure is the major risk factor for developing
COPD. Presently, available COPD treatments focus on suppressing inflammation and
providing bronchodilation. However, these options have varying efficacy in
controlling symptoms and do not reverse or limit the progression of COPD.
Treatments strategies using bacterial-derived products have shown promise in
diseases characterized by inflammation and immune dysfunction. This study
investigated for the first time whether a novel immunotherapy produced from
inactivated Klebsiella (hereafter referred to as KB) containing all the major
Klebsiella macromolecules, could attenuate cigarette smoke exposure-induced
immune responses. We hypothesized that KB, by re-directing damaging immune
responses, would attenuate cigarette smoke-induced lung inflammation and
bronchoalveolar (BAL) cytokine and chemokine production. METHODS: KB was
administered via a subcutaneous injection prophylactically before initiating a 3
week acute nose-only cigarette smoke exposure protocol. Control mice received
placebo injection and room air. Total BAL and differential cell numbers were
enumerated. BAL and serum were analysed for 31 cytokines, chemokines, and growth
factors. Lung tissue and blood were analysed for Ly6CHI monocytes/macrophages and
neutrophils. Body weight and clinical scores were recorded throughout the
experiment. RESULTS: We demonstrate that KB treatment attenuated cigarette smoke
induced lung inflammation as shown by reductions in levels of BAL IFNgamma,
CXCL9, CXCL10, CCL5, IL-6, G-CSF, and IL-17. KB additionally attenuated the
quantity of BAL lymphocytes and macrophages. In parallel to the attenuation of
lung inflammation, KB induced a systemic immune activation with increases in
Ly6CHI monocytes/macrophages and neutrophils. CONCLUSIONS: This is the first
demonstration that subcutaneous administration of a microbial-based immunotherapy
can attenuate cigarette smoke-induced lung inflammation, and modulate BAL
lymphocyte and macrophage levels, while inducing a systemic immune activation and
mobilization. These data provide a foundation for future studies exploring how KB
may be used to either reverse or prevent progression of established emphysema and
small airways disease associated with chronic cigarette smoke exposure. The data
suggest the intriguing possibility that KB, which stimulates rather than
suppresses systemic immune responses, might be a novel means by which the course
of COPD pathogenesis may be altered.
PMID- 28506309
TI - Social isolation and cancer management - advanced rectal cancer with patient
delay following the 2011 triple disaster in Fukushima, Japan: a case report.
AB - BACKGROUND: Little is known about the effects of social isolation in the elderly
on their process of gaining health information and seeking health care. CASE
PRESENTATION: In March 2011, Fukushima, Japan experienced an earthquake, tsunami,
and nuclear disaster, also known as Japan's triple disaster. In June 2016, an 80
year-old Japanese man, who lived alone after divorce at the age of 42, presented
to our hospital with bloody stools and dizziness. Although his bloody stools
initially occurred in May 2015, a year earlier, he did not pursue the possibility
of malignancy. He was diagnosed as having stage IIIA rectal cancer. Detailed
history taking revealed that he experienced social isolation after the disaster,
due to the evacuation of his friends, losing his regular opportunities for
socialization. He additionally reported that the current diagnosis of rectal
cancer made him feel he had lost his health in addition to his social
relationships. Although radical surgery was attempted, it failed to resect the
lesion completely, and thereafter his disease gradually progressed. As support
from family or friends was not available, he was not able to receive palliative
radiation therapy or home-based care in his end-of-life period. He died at a long
term care facility in February 2017. CONCLUSIONS: This case suggests that intense
social isolation after the Fukushima disaster was a likely contributor to the
patient delay, poor treatment course, and poor outcome of an elderly patient with
rectal cancer. Direct communication with family and friends may play an
indispensable role in increasing health awareness and promoting health-seeking
behaviors, and in the midst of social isolation, elderly patients with cancer may
lose these opportunities and experience increased risk of patient delay. Although
health care providers may be able to alleviate isolation-induced delay by
promoting cancer knowledge and awareness widely among local residents, policy-led
interventions at the community level may be essential to reducing social
isolation and its health consequences.
PMID- 28506310
TI - Unexpected evolutionarily conserved rapid effects of viral infection on oxytocin
receptor and TGF-beta/pSmad3.
AB - BACKGROUND: shRNA lentiviral vectors are extensively used for gene knockdowns in
mammalian cells, and non-target shRNAs typically are considered the proper
experimental control for general changes caused by RNAi. However, the effects of
non-target lentivirus controls on the modulation of cell signaling pathways
remain largely unknown. In this study, we evaluated the effect of control
lentiviral transduction on oxytocin receptor (OXTR) expression through the
ERK/MAPK pathway in mouse and human skeletal muscle cells, on myogenic activity,
and in vivo on mouse muscle regeneration. Furthermore, we mined published data
for the influence of viral infections on OXTR levels in human populations and
found that unrelated viral pathologies have a common consequence: diminished
levels of OXTR. METHODS: We examined the change in OXTR mRNA expression upon
transduction with control and Smad3-targeting viral vectors through real time RT
PCR and Western blotting, and confirmed with immunofluorescence. Changes in Smad3
and OXTR expression were examined both in vitro with mouse and human myoblasts
and in vivo in mouse satellite cells. The general effects of viral infections on
OXTR downregulation in humans were also examined by analyzing published Gene
Expression Omnibus (GEO) datasets. The change in myoblast myogenic activity
caused by the viral transduction (the percent of Pax7 + Ki67+ cells) was examined
by immunofluorescence. RESULTS: Results shown in this work establish that
lentiviral control vectors significantly downregulate OXTR expression at mRNA and
protein levels and diminish key downstream effectors of OXTR, ERK signaling,
reducing the myogenic proliferation of infected cells. This effect is
evolutionarily conserved between mouse and human myogenic cells, and it manifests
in satellite cells after control lentiviral transduction of mice in vivo.
Furthermore, an examination of published datasets uncovered similar OXTR
downregulation in humans that are afflicted with different viral infections.
Additionally, cells transduced with Smad3-targeting shRNA downregulate OXTR even
more than cells transduced with control viruses. CONCLUSIONS: Our work suggests
that experimental cohorts transduced with control viruses may not behave the same
as un-transduced cells and animals, specifically that control viral vectors
significantly change the intensity of key cell-signaling pathways, such as
OXTR/ERK. Our results further demonstrate that lentiviral transduction
significantly decreases myogenic proliferation and suggest that viral infections
in general may play a role in decreasing muscle health and regeneration, a
decline in metabolic health, and a lower sense of well-being, as these rely on
effective OXTR signaling. Additionally, our data suggest pathway crosstalk
between TGF-beta/pSmad3 and OXTR, implying that sustained attenuation of the TGF
beta/pSmad3 pathway will reduce pro-regenerative OXTR/pERK signaling.
PMID- 28506311
TI - One-fourth of the prisoners are underweight in Northern Ethiopia: a cross
sectional study.
AB - BACKGROUND: Despite the fact that prisoners are exposed to different health
problems, prison health problems are often overlooked by researchers and no
previous study has investigated nutritional problems of prisoners in Ethiopia.
METHODS: Cross-sectional data were collected from 809 prisoners from nine major
prison setups in the Tigray region of Ethiopia. A proportional stratified
sampling technique was used to select the total number of participants needed
from each prison site. The outcome of this study was underweight defined as body
mass index (BMI) of less than 18.5 kg/m2. Multivariable binary logistic
regression was performed to identify determinants of underweight at a p-value of
less than 0.05. RESULTS: The prevalence of underweight was 25.2% (95% CI; 22.3%-
28.3%). Khat Chewing (OR = 2.08; 95% CI = 1.17, 3.70) and longer duration of
incarceration (OR = 1.07; 95% CI = 1.01, 1.14) were associated with a
significantly increased risk of underweight. Additionally, previous incarceration
(OR = 1.54; 95% CI = 0.99, 2.42) was a relevant determinant of underweight with a
borderline significance. In contrast, family support (OR = 0.61; 95% CI = 0.43,
0.85) and farmer occupation (OR = 0.59; 95% CI = 0.36, 0.98) compared to those
who were unemployed were important protective determinants significantly
associated with lower risk of underweight. CONCLUSION: In summary, the burden of
underweight was higher among prisoners in Tigray region who had respiratory tract
infections. The study has enhanced our understanding of the determinants of
underweight in the prison population. We strongly recommend that nutritional
support , such as therapeutic feeding programs for severely or moderately
underweight prisoners, and environmental health interventions of the prison
setups should be urgently implemented to correct the uncovered nutritional
problem and its associated factors for improving the health status of prisoners.
PMID- 28506313
TI - Latent variable mixture models to test for differential item functioning: a
population-based analysis.
AB - BACKGROUND: Comparisons of population health status using self-report measures
such as the SF-36 rest on the assumption that the measured items have a common
interpretation across sub-groups. However, self-report measures may be sensitive
to differential item functioning (DIF), which occurs when sub-groups with the
same underlying health status have a different probability of item response. This
study tested for DIF on the SF-36 physical functioning (PF) and mental health
(MH) sub-scales in population-based data using latent variable mixture models
(LVMMs). METHODS: Data were from the Canadian Multicentre Osteoporosis Study
(CaMos), a prospective national cohort study. LVMMs were applied to the ten PF
and five MH SF-36 items. A standard two-parameter graded response model with one
latent class was compared to multi-class LVMMs. Multivariable logistic regression
models with pseudo-class random draws characterized the latent classes on
demographic and health variables. RESULTS: The CaMos cohort consisted of 9423
respondents. A three-class LVMM fit the PF sub-scale, with class proportions of
0.59, 0.24, and 0.17. For the MH sub-scale, a two-class model fit the data, with
class proportions of 0.69 and 0.31. For PF items, the probabilities of reporting
greater limitations were consistently higher in classes 2 and 3 than class 1. For
MH items, respondents in class 2 reported more health problems than in class 1.
Differences in item thresholds and factor loadings between one-class and multi
class models were observed for both sub-scales. Demographic and health variables
were associated with class membership. CONCLUSIONS: This study revealed DIF in
population-based SF-36 data; the results suggest that PF and MH sub-scale scores
may not be comparable across sub-groups defined by demographic and health status
variables, although effects were frequently small to moderate in size. Evaluation
of DIF should be a routine step when analysing population-based self-report data
to ensure valid comparisons amongst sub-groups.
PMID- 28506312
TI - Pathomimetic avatars reveal divergent roles of microenvironment in invasive
transition of ductal carcinoma in situ.
AB - BACKGROUND: The breast tumor microenvironment regulates progression of ductal
carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). However, it is
unclear how interactions between breast epithelial and stromal cells can drive
this progression and whether there are reliable microenvironmental biomarkers to
predict transition of DCIS to IDC. METHODS: We used xenograft mouse models and a
3D pathomimetic model termed mammary architecture and microenvironment
engineering (MAME) to study the interplay between human breast myoepithelial
cells (MEPs) and cancer-associated fibroblasts (CAFs) on DCIS progression.
RESULTS: Our results show that MEPs suppress tumor formation by DCIS cells in
vivo even in the presence of CAFs. In the in vitro MAME model, MEPs reduce the
size of 3D DCIS structures and their degradation of extracellular matrix. We
further show that the tumor-suppressive effects of MEPs on DCIS are linked to
inhibition of urokinase plasminogen activator (uPA)/urokinase plasminogen
activator receptor (uPAR)-mediated proteolysis by plasminogen activator inhibitor
1 (PAI-1) and that they can lessen the tumor-promoting effects of CAFs by
attenuating interleukin 6 (IL-6) signaling pathways. CONCLUSIONS: Our studies
using MAME are, to our knowledge, the first to demonstrate a divergent interplay
between MEPs and CAFs within the DCIS tumor microenvironment. We show that the
tumor-suppressive actions of MEPs are mediated by PAI-1, uPA and its receptor,
uPAR, and are sustained even in the presence of the CAFs, which themselves
enhance DCIS tumorigenesis via IL-6 signaling. Identifying tumor
microenvironmental regulators of DCIS progression will be critical for defining a
robust and predictive molecular signature for clinical use.
PMID- 28506314
TI - Application of intraoperative limb-length measurement by a new osteotomy device
in hemiarthroplasty for treating femoral neck fracture.
AB - BACKGROUND: Limb length discrepancy is one of the most common complications after
hip arthroplasty. We developed a device - intraoperative limb-length measurement
and osteotomy device (ILMOD), and applied it to patients who were treated with
hemiarthroplasty for femoral neck fracture to improve limb length discrepancy by
providing an accurate osteotomy during hemi-arthroplasty. METHODS: Between April
2012 and October 2013, 65 patients were treated with hip hemiarthroplasty for
femoral neck fracture at our trauma center. 31 patients met the inclusion
criteria and were randomly enrolled into two groups ILMOD group and control
group. Hemiarthroplasty in this study was performed with cement fixation.
Treatment-related measurements such as the operation time, attempts of osteotomy,
and the volume of intra-operative blood loss were collected. In both groups,
postoperative (1 month) radiologic analysis on anteroposterior weight-bearing
pelvic view was performed to evaluate limb length discrepancy. RESULTS: The
results showed significant improvement in limb length discrepancy in ILMOD group,
and analysis of postoperative radiographs found the mean length difference is 2.1
+/- 1.9 mm in ILMOD group compared to 8.8 +/- 5.1 mm in control group (P <
0.0001). No complications associated with the use of the device were reported,
and none of the patients complained of the discomfort related to limb-length
discrepancy after surgery. The average intra-operative time was significantly
longer in ILMOD group (84.9 +/- 9.2 min) compared to that in control group (70.9
+/- 10.2 min) (P = 0.0004). CONCLUSIONS: The ILMOD is an effective device that
can be used easily for intraoperative limb length measurement and osteotomy
during hemiarthroplasty. This method is applicable with Kocher-Langenbeck
approach, and the technique could also be used in total hip arthroplasty. TRIAL
REGISTRATION: Chinese Clinical Trial Registry ChiCTR-OOC-15005904 . Registered 30
Junuary 2015.
PMID- 28506315
TI - Molecular mechanisms underlying osteoarthritis development: Notch and NF-kappaB.
AB - Osteoarthritis (OA) is a multi-factorial and highly prevalent joint disorder
worldwide. Since the establishment of murine surgical knee OA models in 2005,
many of the key molecules and signalling pathways responsible for OA development
have been identified. Here we review the roles of two multi-functional signalling
pathways in OA development: Notch and nuclear factor kappa-light-chain-enhancer
of activated B cells. Previous studies have identified various aspects of
articular chondrocyte regulation by these pathways. However, comprehensive
understanding of the molecular networks regulating articular cartilage
homeostasis and OA pathogenesis is needed.
PMID- 28506316
TI - Characterization of novel Omp31 antigenic epitopes of Brucella melitensis by
monoclonal antibodies.
AB - BACKGROUND: Brucellosis is a severe zoonotic disease worldwide. Detection and
identification of Brucella species are essential to prevent or treat brucellosis
in humans and animals. The outer membrane protein-31 (Omp31) is a major protein
of Brucellae except for B. abortus, while the Omp31 antigenic epitopes have not
been extensively characterized yet. RESULTS: A total of 22 monoclonal antibodies
(mAbs) were produced against Omp31 of Brucella (B.) melitensis, of which 13
recognized five linear epitopes, 7 reacted with semi-conformational epitopes and
2 reacted with conformational epitopes, respectively. The mAb isotypes were 11
(50%) IgG2a, 5 (23%) IgG1 and 6 (27%) IgM. On the basis of epitope recognition
and reactivity levels, 8 mAbs including 3 IgM and 5 IgG clones were considered as
highly reactive and potentially diagnostic antibodies. Among these mAbs, 7A3
(IgG1), 5B1 (IgG2a), 2C1 (IgG2a) and 5B3 (IgG2a) reacted with differently
conserved linear epitopes of B. melitensis, B. ovis, B. suis and B. canis
strains, while 5H3 (IgG2a) highly reacted with a conformational epitope of Omp31
when tested with several immunoassays. CONCLUSIONS: These potent monoclonal
antibodies can be used for identifying Omp31 antigens or detecting B. melitensis
and other Brucella species beyond B. abortus in vitro or in vivo.
PMID- 28506317
TI - Changes in microbial ecology after fecal microbiota transplantation for recurrent
C. difficile infection affected by underlying inflammatory bowel disease.
AB - BACKGROUND: Gut microbiota play a key role in maintaining homeostasis in the
human gut. Alterations in the gut microbial ecosystem predispose to Clostridium
difficile infection (CDI) and gut inflammatory disorders such as inflammatory
bowel disease (IBD). Fecal microbiota transplantation (FMT) from a healthy donor
can restore gut microbial diversity and pathogen colonization resistance;
consequently, it is now being investigated for its ability to improve
inflammatory gut conditions such as IBD. In this study, we investigated changes
in gut microbiota following FMT in 38 patients with CDI with or without
underlying IBD. RESULTS: There was a significant change in gut microbial
composition towards the donor microbiota and an overall increase in microbial
diversity consistent with previous studies after FMT. FMT was successful in
treating CDI using a diverse set of donors, and varying degrees of donor stool
engraftment suggesting that donor type and degree of engraftment are not drivers
of a successful FMT treatment of CDI. However, patients with underlying IBD
experienced an increased number of CDI relapses (during a 24-month follow-up) and
a decreased growth of new taxa, as compared to the subjects without IBD.
Moreover, the need for IBD therapy did not change following FMT. These results
underscore the importance of the existing gut microbial landscape as a decisive
factor to successfully treat CDI and potentially for improvement of the
underlying pathophysiology in IBD. CONCLUSIONS: FMT leads to a significant change
in microbial diversity in patients with recurrent CDI and complete resolution of
symptoms. Stool donor type (related or unrelated) and degree of engraftment are
not the key for successful treatment of CDI by FMT. However, CDI patients with
IBD have higher proportion of the original community after FMT and lack of
improvement of their IBD symptoms and increased episodes of CDI on long-term
follow-up.
PMID- 28506318
TI - The association between time scarcity, sociodemographic correlates and
consumption of ultra-processed foods among parents in Norway: a cross-sectional
study.
AB - BACKGROUND: Use of ultra-processed foods has expanded rapidly over the last
decades and high consumption has been positively associated with risk of e.g.
overweight, obesity and type 2 diabetes. Ultra-processed foods offer convenience
as they require minimal time for preparation. It is therefore reasonable to
assume that such foods are consumed more often among people who experience time
scarcity. The main aim of this study was to investigate the association between
time scarcity and consumption of ultra-processed foods among parents of 2-year
olds in Norway. A secondary aim was to investigate the association between
sociodemographic correlates, weight status and consumption of ultra-processed
foods. METHODS: This cross-sectional study included 497 participants. Chi-square
and cross tabulations were used to calculate proportions of high vs. low
consumption of ultra-processed foods in relation to time scarcity,
sociodemographic correlates and weight status. Binary logistic regression
analyses were performed to test the relationship between independent variables
and consumption of ultra-processed foods. RESULTS: Participants reporting medium
and high time scarcity were more likely to have a high consumption of ultra
processed dinner products (OR = 3. 68, 95% CI = 2. 32-5.84 and OR = 3.10, 1.80
5.35, respectively) and fast foods (OR = 2.60, 1.62-4.18 and OR = 1.90, 1.08
3.32, respectively) compared to those with low time scarcity. Further,
participants with medium time scarcity were more likely to have a high
consumption of snacks and soft drinks compared to participants with low time
scarcity (OR = 1.63, 1.06-2.49). Finally, gender, ethnicity, educational level,
number of children in the household and weight status were identified as
important factors associated with the consumption of certain types of ultra
processed foods. CONCLUSIONS: Results from the present study showed that time
scarcity, various sociodemographic factors and weight status was associated with
consumption of processed foods. Future studies with a longitudinal design are
needed to further explore these patterns over a longer period of time.
PMID- 28506319
TI - Validation of the Italian version of the Laval questionnaire: health-related
quality of life in subjects with obesity.
AB - BACKGROUND: Obesity is associated to increased risk of metabolic comorbidity as
well as increased mortality. Notably, obesity is also associated to the
impairment of the psychological status and of quality of life. Only three
questionnaires are available in the Italian language evaluating the health
related quality of life in subjects with obesity. The aim of the present study
was to test the validity and reliability of the Italian version of the Laval
Questionnaire. METHODS: The original French version was translated into Italian
and back-translated by a French native speaker. 273 subjects with obesity (Body
Mass Index >= 30 kg/m2) were enrolled; the Italian version of the Laval
Questionnaire and the O.R.Well-97 questionnaire were administered in order to
assess health- related quality of life. The Laval questionnaire consists of 44
items distributed in 6 domains (symptoms, activity/mobility, personal
hygiene/clothing, emotions, social interaction, sexual life). Disability and
overall psychopathology levels were assessed through the TSD-OC test (SIO test
for obesity correlated disabilities) and the SCL-90 (Symptom Checklist-90)
questionnaire, respectively. To verify the validity of the Italian version, the
analysis of internal consistency, test-retest reliability, and construct validity
were performed. RESULTS: The observed proportion of agreement concordance of
results was 50.2% with Cohen's K = 0.336 (CI 95%: 0.267-0.404), indicating a fair
agreement between the two tests. Test-retest correlation was statistically
significant (rho = 0.82; p < 0.01); validity (standardized Chronbach's alpha) was
considered reliable (alpha > 0.70). The analysis of construct validity showed a
statistically significant association in terms of both total score (rho = -0.66)
and scores at each single domain (p < 0.01). A high correlation (p < 0.01) was
observed between Laval questionnaire total and single domain scores and other
related measures (Body Mass Index, TSD-OC scores, SCL-90 global severity index),
revealing a high construct validity of the test. CONCLUSIONS: The Italian version
of the Laval Questionnaire is a valid and reliable measure to assess the health
related quality of life in subjects with obesity.
PMID- 28506321
TI - Work Dissatisfaction and Sleep Problems among Canadians in the Latter Half of
Life.
AB - This study examined the relationship between work dissatisfaction and sleep
problems among Canadian adults in the latter half of life, as well as how gender
and social contact moderate this relationship. Data were obtained from the
Canadian General Social Survey, Cycle 21 (2007), which sampled adults aged 45 and
older in 2007. Analyses focused on individuals with employment as their main
activity. Analyses show that work dissatisfaction positively predicts trouble
sleeping. There are no significant gender differences in this relationship.
Social contact with friends buffers this relationship, but social contact with
family does not, and buffering does not vary significantly between men and women.
This research contributes to knowledge on sleep problems by showing that work
dissatisfaction is adversely associated with sleep problems among Canadians in
the latter half of life, but social contact with friends can weaken this
deleterious relationship.
PMID- 28506320
TI - Costs associated with failure to respond to treatment among patients with
rheumatoid arthritis initiating TNFi therapy: a retrospective claims analysis.
AB - BACKGROUND: Tumor necrosis factor inhibitors (TNFi) are common second-line
treatments for rheumatoid arthritis (RA). This study was designed to compare the
real-world clinical and economic outcomes between patients with RA who responded
to TNFi therapy and those who did not. METHODS: For this retrospective cohort
analysis we used medical and pharmacy claims from members of 14 large U.S.
commercial health plans represented in the HealthCore Integrated Research
Database. Adult patients (aged >=18 years) diagnosed with RA and initiating TNFi
therapy (index date) between 1 January 2007 and 30 April 2014 were included in
the study. Treatment response was assessed using a previously developed and
validated claims-based algorithm. Patients classified as treatment responders in
the 12 months postindex were matched 1:1 to nonresponders on important baseline
characteristics, including sex, age, index TNFi agent, and comorbidities. The
matched cohorts were then compared on their all-cause and RA-related healthcare
resource use, and costs were assessed from a payer perspective during the first,
second, and third years postindex using parametric tests, regressions, and a
nonparametric bootstrap. RESULTS: A total of 7797 patients met the study
inclusion criteria, among whom 2337 (30%) were classified as treatment
responders. The responders had significantly lower all-cause hospitalizations,
emergency department visits, and physical/occupational therapy visits than
matched nonresponders during the first-year postindex. Mean total all-cause
medical costs were $5737 higher for matched nonresponders, largely driven by
outpatient visits and hospitalizations. Mean all-cause pharmacy costs (excluding
costs of biologics) were $354 higher for matched nonresponders. Mean RA-related
pharmacy costs (conventional synthetic and biologic drugs), however, were $8579
higher in the responder cohort, driven by higher adherence to their index TNFi
agent (p < 0.01 for all comparisons). A similar pattern of cost differentiation
was observed over years 2 and 3 of follow-up. CONCLUSIONS: In this real-world
study we found that, compared with matched nonresponders, patients who responded
to TNFi treatments had lower all-cause medical, pharmacy, and total costs
(excluding biologics) up to 3 years from initiation of TNFi therapy. These cost
differences between the two cohorts provide a considerable offset to the cost of
RA medications and should encourage close monitoring of treatment response to
minimize disease progression with appropriate therapy choices.
PMID- 28506322
TI - Transcatheter closure of a membranous ventricular septal defect in a 1.8-kg
infant using Amplatzer Duct Occluder II additional size device.
AB - Catheter closure of membranous ventricular septal defects is generally not
considered feasible in small infants. We report the successful closure of a
membranous ventricular septal defect in a 1.8-kg infant with bilateral femoral
artery occlusion using Amplatzer Duct Occluder II additional size device. The
ventricular septal defect was crossed from the right ventricle, and the device
was deployed using transthoracic echocardiographic guidance.
PMID- 28506323
TI - Transcatheter correction of Scimitar syndrome: occlusion of abnormal pulmonary
venous drainage and vascular supply in an infant.
AB - Treatment of Scimitar syndrome is usually surgical; however, if there is "dual
drainage" - that is, one to the inferior caval vein and the other to the left
atrium - it is possible to successfully treat this anomaly via a less-invasive
transcatheter approach. We report a case of Scimitar syndrome in a 21-month-old,
male infant successfully treated with transcatheter embolisation.
PMID- 28506324
TI - Preposition accuracy on a sentence repetition task in school age Spanish-English
bilinguals.
AB - Preposition knowledge is important for academic success. The goal of this project
was to examine how different variables such as English input and output, Spanish
preposition score, mother education level, and age of English exposure (AoEE) may
have played a role in children's preposition knowledge in English. 148 Spanish
English children between 7;0 and 9;11 produced prepositions in English and
Spanish on a sentence repetition task from an experimental version of the
Bilingual English Spanish Assessment Middle Extension (Pena, Bedore, Gutierrez
Clellen, Iglesias & Goldstein, in development). English input and output
accounted for most of the variance in English preposition score. The importance
of language-specific experiences in the development of prepositions is discussed.
Competition for selection of appropriate prepositions in English and Spanish is
discussed as potentially influencing low overall preposition scores in English
and Spanish.
PMID- 28506325
TI - A proposed analytic framework for determining the impact of an antimicrobial
resistance intervention.
AB - Antimicrobial use (AMU) is increasingly threatened by antimicrobial resistance
(AMR). The FDA is implementing risk mitigation measures promoting prudent AMU in
food animals. Their evaluation is crucial: the AMU/AMR relationship is complex; a
suitable framework to analyze interventions is unavailable. Systems science
analysis, depicting variables and their associations, would help integrate
mathematics/epidemiology to evaluate the relationship. This would identify
informative data and models to evaluate interventions. This National Institute
for Mathematical and Biological Synthesis AMR Working Group's report proposes a
system framework to address the methodological gap linking livestock AMU and AMR
in foodborne bacteria. It could evaluate how AMU (and interventions) impact AMR.
We will evaluate pharmacokinetic/dynamic modeling techniques for projecting AMR
selection pressure on enteric bacteria. We study two methods to model phenotypic
AMR changes in bacteria in the food supply and evolutionary genotypic analyses
determining molecular changes in phenotypic AMR. Systems science analysis
integrates the methods, showing how resistance in the food supply is explained by
AMU and concurrent factors influencing the whole system. This process is updated
with data and techniques to improve prediction and inform improvements for
AMU/AMR surveillance. Our proposed framework reflects both the AMR system's
complexity, and desire for simple, reliable conclusions.
PMID- 28506326
TI - A model to infer the demographic structure evolution of endangered donkey
populations.
AB - Stemming from The Worldwide Donkey Breeds Project, an initiative aiming at
connecting international researchers and entities working with the donkey
species, molecularly tested pedigree analyses were carried out to study the
genetic diversity, structure and historical evolution of the Andalusian donkey
breed since the 1980s to infer a model to study the situation of international
endangered donkey breeds under the remarkably frequent unknown genetical
background status behind them. Demographic and genetic variability parameters
were evaluated using ENDOG (v4.8). Pedigree completeness and generation length
were quantified for the four gametic pathways. Despite mean inbreeding was low,
highly inbred animals were present in the pedigree. Average coancestry,
relatedness, and non-random mating degree trends were computed. The effective
population size based on individual inbreeding rate was about half when based on
individual coancestry rate. Nei's distances and equivalent subpopulations number
indicated differentiated farms in a highly structured population. Although
genetic diversity loss since the founder generations could be considered small,
intraherd breeding policies and the excessive contribution of few ancestors to
the gene pool could lead to narrower pedigree bottlenecks. Long average
generation intervals could be considered when reducing inbreeding. Wright's
fixation statistics indicated slight inbreeding between farms. Pedigree
shallowness suggested applying new breeding strategies to reliably estimate
descriptive parameters and control the negative effects of inbreeding, which
could indeed, mean the key to preserve such valuable animal resources avoiding
the extinction they potentially head towards, making the present model become an
international referent when assessing endangered donkey populations.
PMID- 28506328
TI - The effect of dietary faba bean and non-starch polysaccharide degrading enzymes
on the growth performance and gut physiology of young turkeys.
AB - The aim of this study was to investigate the effect of dietary replacement of
soya bean meal (SBM) with faba bean (FB) and a blend of non-starch polysaccharide
(NSP) degrading enzymes on the gastrointestinal function, growth performance and
welfare of young turkeys (1 to 56 days of age). An experiment with a 2*2
factorial design was performed to compare the efficacy of four diets: a SBM-based
diet and a diet containing FB, with and without enzyme supplementation (C, FB, CE
and FBE, respectively). In comparison with groups C, higher dry matter content
and lower viscosity of the small intestinal digesta were noted in groups FB. The
content of short-chain fatty acids (SCFAs) in the small intestinal digesta was
higher in groups FB, but SCFA concentrations in the caecal digesta were
comparable in groups C and FB. In comparison with control groups, similar BW
gains, higher feed conversion ratio (FCR), higher dry matter content of excreta
and milder symptoms of footpad dermatitis (FPD) were noted in groups FB. Enzyme
supplementation increased the concentrations of acetate, butyrate and total
SCFAs, but it did not increase the SCFA pool in the caecal digesta. The enzymatic
preparation significantly improved FCR, reduced excreta hydration and the
severity of FPD in turkeys. It can be concluded that in comparison with the SBM
based diet, the diet containing 30% of FB enables to achieve comparable BW gains
accompanied by lower feed efficiency during the first 8 weeks of rearing. Non
starch polysaccharide-degrading enzymes can be used to improve the nutritional
value of diets for young turkeys, but more desirable results of enzyme
supplementation were noted in the SBM-based diet than in the FB-based diet.
PMID- 28506327
TI - The Seasonal Variability in Surgical Site Infections and the Association With
Warmer Weather: A Population-Based Investigation.
AB - OBJECTIVE To determine whether the seasonality of surgical site infections (SSIs)
can be explained by changes in temperature. DESIGN Retrospective cohort analysis.
SETTING The National Inpatient Sample database. PATIENTS All hospital discharges
with a primary diagnosis of SSI from 1998 to 2011 were considered cases.
Discharges with a primary or secondary diagnoses of specific surgeries commonly
associated with SSIs from the previous and current month served as our "at risk"
cohort. METHODS We modeled the national monthly count of SSI cases both
nationally and stratified by region, sex, age, and type of institution. We used
data from the National Climatic Data Center to estimate the monthly average
temperatures for all hospital locations. We modeled the odds of having a primary
diagnosis of SSI as a function of demographics, payer, location, patient
severity, admission month, year, and the average temperature in the month of
admission. RESULTS SSI incidence is highly seasonal, with the highest SSI
incidence in August and the lowest in January. During the study period, there
were 26.5% more cases in August than in January (95% CI, 23.3-29.7). Controlling
for demographic and hospital-level characteristics, the odds of a primary SSI
admission increased by roughly 2.1% per 2.8 degrees C (5 degrees F) increase in
the average monthly temperature. Specifically, the highest temperature group,
>32.2 degrees C (>90 degrees F), was associated with an increase in the odds of
an SSI admission of 28.9% (95% CI, 20.2-38.3) compared to temperatures <4.4
degrees C (<40 degrees F). CONCLUSIONS At population level, SSI risk is highly
seasonal and is associated with warmer weather. Infect Control Hosp Epidemiol
2017;38:809-816.
PMID- 28506329
TI - What to do when a patient wants to record a patient-physician interaction in the
emergency department.
AB - Recent technological advances allow for instantaneous high quality video and
audio recordings with the touch of a button. In Canada, patient privacy is highly
regulated by provincial legislation, although patients themselves have little in
the way of laws or regulations to observe. Patients taking video recordings of
their own medical care does not currently fall under any of the provincial
privacy laws. With no such governance for the general public, patients generally
have greater freedom to record a patient-physician interaction. Unfortunately,
there are no official policies from the provincial physician colleges regarding
how best to proceed in these circumstances. Therefore, the onus is on individual
hospitals and emergency departments (EDs) to develop their own policy on video
recordings. A policy should ideally cover possible recording devices, locations,
staff involved, and mandate that a written consent form be included with the
patient's chart. While every request should be considered individually,
physicians should generally not feel compelled to agree to the patient recording
the clinical encounter. Patients are legally allowed to record a patient
physician interaction without consent of their physician, because the patient can
provide the "one-party consent" for the conversation to be recorded. Physicians
should accept the possibility that they are being recorded at all times and
should strive to communicate as clearly and effectively as possible. Physicians
should strive to provide the same level of care that they would even if they were
not being recorded, and not let it interfere with their clinical decision-making.
PMID- 28506330
TI - Edwards valve-in-valve implantation in tricuspid position.
AB - We present two cases of percutaneous Sapien XT valve-in-valve implantation in the
tricuspid position: a 20-year-old man with severe congenital pulmonary stenosis
and percutaneous valvuloplasty, who required surgical implantation of two
protheses, pulmonary and tricuspid, and a 12-year-old boy with CHD and a
degenerated tricuspid prosthesis. We implanted three Sapien XT valve-in-valves,
two in the tricuspid position and one in the pulmonic position. Sapien XT valve
in-valve implantation in the tricuspid position is feasible and can decrease the
number of surgeries in CHD patients.
PMID- 28506331
TI - Glucocorticoids for treating paediatric pulmonary hypertension: a novel use for a
common medication.
AB - Laboratory investigations have shown the role of inflammation in the pathogenesis
of pulmonary hypertension and improvement after anti-inflammatory drugs. Despite
these observations, reports on the use of steroids to treat pulmonary
hypertension in humans are absent from the literature. In this article, we report
the use of glucocorticoids in the treatment of two children with pulmonary
hypertension, demonstrating its potential utility.
PMID- 28506332
TI - Correspondence analysis to evaluate the transmission of Staphylococcus aureus
strains in two New York State maximum-security prisons.
AB - Prisons/jails are thought to amplify the transmission of Staphylococcus aureus
(SA) particularly methicillin-resistant SA infection and colonisation. Two
independently pooled cross-sectional samples of detainees being admitted or
discharged from two New York State maximum-security prisons were used to explore
this concept. Private interviews of participants were conducted, during which the
anterior nares and oropharynx were sampled and assessed for SA colonisation. Log
binomial regression and correspondence analysis (CA) were used to evaluate the
prevalence of colonisation at entry as compared with discharge. Approximately 51%
of admitted (N = 404) and 41% of discharged (N = 439) female detainees were
colonised with SA. Among males, 59% of those admitted (N = 427) and 49% of those
discharged (N = 393) were colonised. Females had a statistically significant
higher prevalence (1.26: P = 0.003) whereas males showed no significant
difference (1.06; P = 0.003) in SA prevalence between entry and discharge. CA
demonstrated that some strains, such as spa types t571 and t002, might have an
affinity for certain mucosal sites. Contrary to our hypothesis, the prison
setting did not amplify SA transmission, and CA proved to be a useful tool in
describing the population structure of strains according to time and/or mucosal
site.
PMID- 28506333
TI - @Home eTherapy Service for People with Common Mental Health Problems: an
Evaluation.
AB - BACKGROUND: Ensuring rapid access to psychological interventions is a priority of
mental health services. The involvement of peer workers to support the delivery
of more accessible treatment options such as computerized cognitive behaviour
therapy (CCBT) is recognized. AIMS: To evaluate the implementation of a third
sector remote CCBT @Home eTherapy service for people experiencing common mental
health problems supported by individuals with lived experience. METHOD: Supported
CCBT packages with telephone support were delivered over a 30-month period. Self
complete measures identifying levels of depression, anxiety and functioning were
administered at each treatment appointment. RESULTS: Over 2000 people were
referred to the @Home eTherapy service; two-thirds attended an initial assessment
and 53.4% of referrals assigned to CCBT completed treatment. Statistically
significant improvements in anxiety, depression and functioning were found, with
61.6% of treated clients meeting recovery criteria. CONCLUSIONS: The service
meets Improving Access to Psychological Therapies (IAPT) key performance targets,
and is comparable to other IAPT services using CCBT. Evidence for the successful
implementation of such a service by a third sector organization is provided.
PMID- 28506334
TI - [MECP2 duplication syndrome: a clinical analysis of three cases and literature
review].
AB - MECP2 duplication syndrome (MDS) is a rare pediatric disease and mainly manifests
as delayed motor development, language loss or delay, recurrent infection, severe
intellectual disability, epilepsy, autistic symptoms, and early infantile
hypotonia. In this article, the three children with this disease were all boys.
Cases 1 and 2 had delayed motor development, and language loss or delay as
initial manifestations, and case 3 had recurrent infection as initial
manifestation. Physical examination showed hypotonia and negative pathological
signs in each case. Case 1 had tonic-clonic seizures and electroencephalography
showed focal seizures, for which he was given oxcarbazepine, levetiracetam, and
clonazepam as the antiepileptic treatment to control seizures. Case 3 experienced
one absence seizure and three head-nodding seizures with normal
electroencephalographic findings during these seizures, and therefore, he was not
given antiepileptic treatment. In each case, recurrent infection was improved
with the increase in age, but there were no significant improvements in language
or intelligence. Array-based comparative genomic hybridization (aCGH) showed
MECP2 duplication in X chromosome in each case, and so they were diagnosed with
MDS. MDS should be considered for children with delayed development complicated
by recurrent infection and epileptic seizures, and early aCGH helps with the
diagnosis of this disease.
PMID- 28506335
TI - [MECP2 gene and MECP2-related diseases].
PMID- 28506336
TI - [Alpers-Huttenlocher syndrome caused by a novel compound heterozygous mutation of
POLG gene: a case report].
PMID- 28506337
TI - [Mitochondrial diseases and epilepsy].
PMID- 28506338
TI - [Clinical efficacy of compound glycyrrhizin tablets in the treatment of children
with nonalcoholic fatty liver disease].
AB - Department of Pediatrics, First Affiliated Hospital of Nanjing Medical
University, Nanjing 210029, China. zhuchuanlong@jsph.org.cn.
PMID- 28506339
TI - [Effect of allergic rhinitis on disease condition and treatment in patients with
juvenile-onset systemic lupus erythematosus].
AB - OBJECTIVE: To investigate the effect of allergic rhinitis (AR) and its
intervention on disease condition and medications in patients with juvenile-onset
systemic lupus erythematosus (JSLE). METHODS: The clinical data of 96 children
diagnosed with JSLE were collected, and according to the presence or absence of
AR or other allergic diseases, they were divided into AR group (n=44), non-AR
group (n=20), and non-allergic group (n=32). The children in the AR group were
randomly administered with or without intervention (n=22 each). All the children
were given standard JSLE treatment. The systemic lupus erythematosus disease
active index (SLEDAI) and application of hormones and immunosuppressants were
compared between groups. RESULTS: The AR and non-AR groups had significantly
higher SLEDAI scores, daily cumulative doses of glucocorticoids, and number of
types of immunosuppressants used than the non-allergic group before treatment
(P<0.05), while there were no significant differences between the AR and non-AR
groups (P>0.05). After one month of treatment, the AR group with intervention had
significantly lower SLEDAI scores and daily cumulative doses of glucocorticoids
than the AR group without intervention (P<0.05), while there was no significant
difference in the application of immunosuppressants between these two groups
(P>0.05). After 3 and 6 months of treatment, the AR group with intervention had
significantly lower SLEDAI scores, daily cumulative doses of glucocorticoids, and
number of types of immunosuppressants than the AR group without intervention
(P<0.05). CONCLUSIONS: JSLE combined with allergic diseases such as AR has an
adverse effect on disease condition and treatment, and the intervention for AR
helps with the control of JSLE.
PMID- 28506340
TI - [Endocrine and metabolic features of female children with Prader-Willi syndrome:
an analysis of 4 cases].
AB - This article reports the clinical features and endocrine and metabolic features
of 4 children with Prader-Willi syndrome (PWS). All the patients were female and
aged 6-12 years at diagnosis. All of them had clinical manifestations of obesity,
unusual facies, developmental retardation, and intellectual disability. Genetic
detection showed that 2 patients had paternal deletion of the 15q11.2-q13 region,
one patient had maternal autodiploid in the 15q11.2-q13 region, and one patient
had no abnormality in the 15q11.2-q13 region. All patients had varying degrees of
endocrine and metabolic disorders: 2 patients had short stature, among whom one
had delayed appearance of secondary sex characteristics and the other one had
type 2 diabetes; one patient had insulin resistance and no mammary gland
development; one patient had a body height of P3-P10 and precocious puberty.
Patients with PWS have various endocrine disorders, so long-term endocrine follow
up and management is very important.
PMID- 28506341
TI - [Effect of obesity on pulmonary function in asthmatic children of different age
groups].
AB - OBJECTIVE: To study the effect of obesity on pulmonary function in newly
diagnosed asthmatic children of different age groups. METHODS: Two hundred and
ninety-four children with newly diagnosed asthma were classified into preschool
age (<6 years) and school-age (6 to 12.5 years) groups. They were then classified
into obese, overweight, and normal-weight subgroups based on their body mass
index (BMI). All the children underwent pulmonary function tests, including large
airway function tests [forced vital capacity (FVC%) and forced expiratory volume
in one second (FEV1%)] and small airway function tests [maximal expiratory flow
at 25% of vital capacity (MEF25%), maximal expiratory flow at 50% of vital
capacity (MEF50%), and maximal expiratory flow at 75% of vital capacity
(MEF75%)]. RESULTS: The school-age group showed lower FEV1%, MEF25%, and MEF50%
than the preschool-age group (P<0.05) after adjustment for sex and BMI. The
normal-weight children in the school-age group had lower FEV1%, MEF25%, and
MEF50% compared with their counterparts in the preschool-age group (P<0.05). The
overweight children in the school-age group showed lower FVC% and MEF50% than
those in the preschool-age group. However, all the pulmonary function parameters
showed no significant differences between the obese children in the preschool-age
and school-age groups. In the preschool-age group, FVC%, FEV1%, and MEF75% of the
obese children were lower than those of the normal-weight children. In the school
age group, only FVC% and FEV1% showed differences between the obese and normal
weight children (P<0.05). CONCLUSIONS: The effect of obesity on the pulmonary
function varies with age in children with asthma, and the effect is more obvious
in those of preschool age.
PMID- 28506342
TI - [Cardiac autonomic nerve function in obese school-age children].
AB - OBJECTIVE: To analyze the deceleration capacity (DC) of heart rate, acceleration
capacity (AC) of heart rate, and heat rate variability (HRV) in obese school-age
children, and to observe the correlations of BMI with DC, AC, and HRV in these
children. METHODS: A total of 108 obese school-age children were selected,
including 75 cases of ortholiposis and 33 cases of dyslipidemia. A total of 103
healthy school-age children were selected as control group. All the subjects
underwent 24-hour ambulatory electrocardiography. The comparisons of DC, AC, and
HRV were made between the obese and control groups, as well as between children
with ortholiposis and dyslipidemia in the obese group. The correlations of BMI
with DC, AC, and HRV were analyzed in the obese group. RESULTS: The obese group
showed lower DC, standard deviation of normal-to-normal R-R intervals (SDNN),
standard deviation of the average normal-to-normal intervals (SDANN), root mean
square of successive differences (RMSSD), low-frequency power (LF), and high
frequency power (HF) than the control group. The AC of the obese group was
significantly higher than that of the control group (P<0.05). In the obese group,
children with dyslipidemia had significantly lower DC, SDNN, SDANN, RMSSD, LF,
and HF, but significantly higher AC and BMI, as compared with those with
ortholiposis (P<0.01). In the obese group, BMI was negatively correlated with DC,
SDNN, SDANN, RMSSD, and HF (P<0.05), but positively correlated with AC (P<0.05).
CONCLUSIONS: Obese school-age children have impaired autonomic nerve function,
presenting with reduced vagal tone, which is particularly prominent in those with
dyslipidemia. The more obese the children, the lower the vagal tone, which may
increase the risks of cardiovascular diseases.
PMID- 28506343
TI - [Current status of research on infantile cholestatic liver disease in China: a
visualization analysis].
AB - OBJECTIVE: To investigate the current status of research on infantile cholestatic
liver disease in China and future research trends. METHODS: A co-word analysis
was performed in October 2016. Document retrieval and screening were performed in
the Chinese databases CNKI and Wanfang Data using "cholestasis" and "infant" as
key words. Excel 2010 was used to establish a co-occurrence matrix of high
frequency key words, and Ucinet 6.0 and Netdraw were used to develop a visualized
network of these high-frequency key words. RESULTS: A total of 383 articles were
included. The co-occurrence analysis showed that "infant" and "cholestasis" were
the core of research in this field, and "infantile hepatitis syndrome",
"neonate", "intrahepatic", "biliary atresia", "heredity and metabolism",
"hepatitis", "cytomegalovirus", "jaundice", and "conjugated bilirubin" were main
research topics. Most of the other articles focused on "parenteral nutrition",
"hepatobiliary imaging", "gene mutation", and "liver biopsy". There were
relatively few articles on surgical diagnostic techniques and treatment for this
disease. CONCLUSIONS: The research on infantile cholestatic liver disease in
China focuses on etiology and differential diagnosis, and genetic diagnosis has
become a hot topic in recent years. The research on treatment should be enhanced,
and new diagnostic techniques are the research interest in future.
PMID- 28506344
TI - [Novel PHEX gene mutations in patients with X-linked hypophosphatemic rickets: an
analysis of 2 cases].
AB - OBJECTIVE: To investigate PHEX gene mutations in 2 patients with X-linked
hypophosphatemic rickets (XLH) and their families and to clarify the genetic
etiology. METHODS: A retrospective analysis was performed for the clinical data
of two patients with XLH. High-throughput sequencing was used to detect the PHEX
gene, a pathogenic gene of XLH. PCR-Sanger sequencing was used to verify the
distribution of mutations in families. RESULTS: Both patients had novel mutations
in the PHEX gene; one patient had a frameshift mutation, c.931dupC, which caused
early termination of translation and produced the truncated protein
p.Gln311Profs*13; the other patient had a splice site mutation, IVS14+1G>A, which
caused the skipping of exon 15 and produced an incomplete amino acid chain. Their
parents had normal gene phenotypes. CONCLUSIONS: c.931dupC and IVS14+1G>A are two
novel mutations of the PHEX gene and might be the new pathogenic mutations of
XLH.
PMID- 28506345
TI - [Infantile hypophosphatasia caused by a novel compound heterozygous mutation: a
case report and pedigree analysis].
AB - This article reported the clinical features of one child with infantile
hypophosphatasia (HPP) and his pedigree information. The proband was a 5-month
old boy with multiple skeletal dysplasia (koilosternia, bending deformity of both
radii, and knock-knee deformity of both knees), feeding difficulty, reduction in
body weight, developmental delay, recurrent pneumonia and respiratory failure,
and a significant reduction in blood alkaline phosphatase. Among his parents,
sister, uncle, and aunt (other family members did not cooperate with us in the
examination), his parents and aunt had a slight reduction in alkaline phosphatase
and his aunt had scoliosis; there were no other clinical phenotypes or abnormal
laboratory testing results. His ALPL gene mutation came from c.228delG mutation
in his mother and c.407G>A compound heterozygous mutation in his father. His aunt
carried c.228delG mutation. The c.407G>A mutation had been reported as the
pathogenic mutation of HPP, and c.228delG mutation was a novel pathogenic
mutation. Hypophosphatasia is caused by ALPL gene mutation, and ALPL gene
detection is an effective diagnostic method. This study expands the mutation
spectrum of ALPL gene and provides a theoretical basis for genetic diagnosis of
this disease.
PMID- 28506346
TI - [Role of short-latency somatosensory evoked potential in the diagnosis of chronic
inflammatory demyelinating polyneuropathy].
AB - OBJECTIVE: To investigate the role of short-latency somatosensory evoked
potential (SSEP) in the diagnosis of chronic inflammatory demyelinating
polyneuropathy (CIDP). METHODS: A total of 48 children with a confirmed or
suspected CIDP and 40 healthy children were enrolled. Nerve electrophysiological
examination and/or SSEP examination was performed (the children in the healthy
control group only underwent SSEP examination). Four-lead electromyography was
used for nerve electrophysiological examination, including at least 4 motor
nerves and 2 sensory nerves. N6 (elbow potential), N13 (cervical cord potential),
and N20 (cortex potential) of the median nerve and N8 (popliteal fossa
potential), N22 (lumbar cord potential), and P39 (cortex potential) of the tibial
nerve were observed by SSEP examination. RESULTS: Among the 48 children with
CIDP, 35 had demyelination in both motor and sensory nerves, 8 had demyelination
in sensory nerves, and 5 had axonal degeneration. SSEP examination showed that 7
had conduction abnormality in the trunk of the brachial plexus and/or the
posterior root and 33 had damage in the lumbosacral plexus and/or the posterior
root. The 40 children with abnormal findings of SSEP examination included 8
children with affected sensory nerves and 5 children with secondary axonal
degeneration who did not meet the electrophysiological diagnostic criteria for
CIDP. Compared with the healthy control group, the CIDP group had significantly
prolonged latency periods of N13 and N22 (P<0.05). CONCLUSIONS: SSEP can be used
for the auxiliary diagnosis of CIDP, especially in CIDP children with affected
sensory nerves or secondary axonal degeneration.
PMID- 28506347
TI - [Association between autism spectrum disorder and epilepsy in children].
AB - OBJECTIVE: To examine the association between autism spectrum disorder (ASD) and
epilepsy in children. METHODS: A total of 190 children with ASD were enrolled. A
self-designed questionnaire, Childhood Autism Rating Scale, and Autism Behavior
Checklist were used to determine the association between ASD and epilepsy.
RESULTS: Among the 190 children with ASD, 20 (10.5%) had epileptic seizures and
12 (6.3%) were diagnosed with epilepsy. The rates of abnormal physical
development and hearing disorders before the age of one year were significantly
higher in ASD children with epileptic seizures than in those without epileptic
seizures (P<0.05). The ASD children diagnosed with epilepsy and those receiving
epilepsy treatment had a significantly increased rate of abnormal physical
development before the age of one year (P<0.05). The ASD children with epileptic
seizures had poorer sensory responses and behavioral competencies than those
without epileptic seizures (P<0.05). Epilepsy treatment have a positive effect on
behavioral competencies in ASD children (P<0.05). CONCLUSIONS: There is a
significant association between ASD and epilepsy in children. The possibility of
the comorbidity between ASD and epilepsy may be assessed according to the status
of growth and development before the age of one year, sensory responses and
behavioral competencies, and the presence or absence of epileptic seizures.
PMID- 28506348
TI - [Influence of home nurture environment on language development and social emotion
in children with developmental language disorder].
AB - OBJECTIVE: To investigate the influence of home nurture environment on language
development and social emotion in children with developmental language disorder
(DLD). METHODS: The 1-3 Years Child Home Nurture Environment Scale, Gesell
Developmental Scale, and Infant-Toddler Social and Emotional Assessment Scale
were used for the evaluation of 125 children with DLD. A total of 130 children
with normal language development matched for age and sex were enrolled as control
group. RESULTS: Compared with the control group, the DLD group had a
significantly higher proportion of children in a bad home nurture environment and
significantly lower scores of all domains of home nurture environment (P<0.05).
In children with DLD, the home nurture environment score was positively
correlated with the level of language development (r=0.536, P<0.01) and the score
of ability domain in social emotion (r=0.397, P<0.01) and was negatively
correlated with the scores of the domains of explicit behavior, covert behavior,
and imbalance in social emotion (r=-0.455, -0.438, and -0.390 respectively,
P<0.01). Home nurture environment had direct influence on language development in
children with DLD and affected their language development via the mediating
effect of social emotion. CONCLUSIONS: Home nurture environment influences
language development and social emotion in children with DLD, and social emotion
has a partial mediating effect between home nurture environment and language
development.
PMID- 28506349
TI - [Relationship between fever degree and prognosis in children with bacterial
bloodstream infection].
AB - OBJECTIVE: To study the relationship between the degree of fever within 48 hours
of admission and the prognosis in children with bacterial bloodstream infection.
METHODS: This study retrospectively analyzed the clinical data of all patients
diagnosed with sepsis who were admitted to the pediatric intensive care unit
(PICU) of Shengjing Hospital Affiliated to China Medical University between
September 2008 and September 2016. The children with bacterial bloodstream
infection were classified into 5 groups according to the maximum temperature
within 48 hours of admission: <36.5 degrees C group, >=36.5 degrees C group
(normal control), >=37.5 degrees C group, >=38.5 degrees C group, and >=39.5
degrees C group. The mortality was compared between the five groups. Results A
total of 213 children with bacterial bloodstream infection were enrolled,
consisting of 5 cases in the <36.5 degrees C group, 44 cases in the >=36.5
degrees C group, 73 cases in the >=37.5 degrees C group, 69 cases in the >=38.5
degrees C group, and 22 cases in the >=39.5 degrees C group. A total of 48 cases
died among the 213 patients. A significant difference was observed in the
mortality between the five groups (P<0.01). The <36.5 degrees C group and >=39.5
degrees C group had significantly higher mortality than the normal control group.
However, there were no significant differences in the mortality between the
>=37.5 degrees C and >=38.5 degrees C groups and the normal control group.
Conclusions In children with bacterial bloodstream infection, those with a
maximum temperature below 36.5 degrees C or above 39.5 degrees C within 48 hours
of admission have a significantly increased mortality.
PMID- 28506350
TI - [A preliminary study on the disappearance time of influenza virus antigen].
AB - OBJECTIVE: To investigate the antigen clearance time, time to symptom
disappearance, and the association between them using immunofluorescence assay
for dynamic monitoring of influenza virus antigen in children with influenza.
METHODS: A total of 1 063 children suspected of influenza who visited the Hunan
People's Hospital from March to April, 2016 were enrolled. The influenza A/B
virus antigen detection kit (immunofluorescence assay) was used for influenza
virus antigen detection. The children with positive results were given
oseltamivir as the antiviral therapy and were asked to re-examine influenza virus
antigen at 5, 5-7, and 7 days after onset. RESULTS: Of all children suspected of
influenza, 560 (52.68%) had an influenza virus infection. A total of 215 children
with influenza virus infection were followed up. The clearance rate of influenza
virus antigen was 9.8% (21 cases) within 5 days after onset. The cumulative
clearance rate of influenza virus antigen was 32.1% (69 cases) within 5-7 days,
and 98.1% (211 cases) within 7-10 days after onset. Among these children, 6
children (2.8%) achieved the improvement in clinical symptoms within 3 days after
onset. The cumulative rate of symptom improvement was 84.7% (182 cases) within 3
5 days after onset, and 100% achieved the improvement after 5 days of onset.
CONCLUSIONS: The time to improvement in symptoms after treatment is earlier than
antigen clearance time. Almost all of the children achieve influenza virus
antigen clearance 7-10 days after onset. Therefore, it is relatively safe for
children to go back to school within 7-10 days after onset when symptoms
disappear.
PMID- 28506351
TI - [Clinical features and magnetic resonance imaging evaluation of encephalopathy in
high-risk late preterm infants].
AB - OBJECTIVE: To investigate the risk factors, clinical features, and magnetic
resonance imaging (MRI) changes of encephalopathy in high-risk late preterm
infants. METHODS: Head MRI scan was performed for late preterm infants with high
risk factors for brain injury who were hospitalized between January 2009 and
December 2014. The risk factors, clinical features, and head MRI features of
encephalopathy in late preterm infants were analyzed. RESULTS: A total of 1 007
late preterm infants underwent MRI scan, among whom 313 (31.1%) had imaging
features in accordance with the features of encephalopathy of prematurity. Of all
infants, 76.7% had white matter damage. There was no association between the
development of encephalopathy and gestational age in late preterm infants, but
the detection rate of encephalopathy gradually increased with the increasing
birth weight (P<0.05). The logistic regression analysis showed that a history of
resuscitation was an independent risk factor for encephalopathy of prematurity
(P<0.01). CONCLUSIONS: Encephalopathy of prematurity is commonly seen in high
risk late preterm infants, especially white matter damage. A history of
resuscitation is an independent risk factor for encephalopathy in late preterm
infants.
PMID- 28506352
TI - [Effect of breastfeeding versus formula milk feeding on preterm infants in the
neonatal intensive care unit].
AB - OBJECTIVE: To investigate the importance of breastfeeding in preterm infants with
various gestational ages. METHODS: A total of 639 preterm infants with a
gestational age of 28+3-36+6 weeks were enrolled, and according to the feeding
pattern, they were divided into exclusive breastfeeding group (n=237) and formula
milk feeding group (fed with liquid milk for preterm infants; n=402). These two
feeding patterns were compared in terms of their effects on weight gain,
laboratory markers including albumin (Alb) and alkaline phosphatase (ALP),
incidence rate of feeding intolerance, and incidence rates of complications
including necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP).
RESULTS: Compared with the formula milk feeding group, the breastfeeding group
had a significantly faster increase in body weight, a significantly lower
incidence rate of NEC, a significantly higher ALP level, and a significantly
lower Alb level in the preterm infants with a gestational age of 28-30 weeks
(P<0.05); there were no significant differences between the two groups in the
incidence rates of anemia, ROP, bronchopulmonary dysplasia (BPD), and nosocomial
infection and length of hospital stay (P>0.05). For the preterm infants with a
gestational age of 31-33 weeks, the breastfeeding group had a significantly
faster increase in body weight, a significantly lower incidence rate of feeding
intolerance, a significantly shorter length of hospital stay, and a significantly
higher ALP level (P<0.05); there were no significant differences between the two
groups in the incidence rates of NEC, anemia, ROP, BPD, and nosocomial infection
and the Alb level (P>0.05). For the preterm infants with a gestational age of 34
36 weeks, there were no significant differences in these indices between the two
groups (P>0.05). CONCLUSIONS: Breastfeeding plays an important role in increasing
body weight, reducing the incidence rates of feeding intolerance and NEC, and
shortening the length of hospital stay in preterm infants with a gestational age
of 28-33 weeks.
PMID- 28506353
TI - [Effect of baicalin on ATPase and LDH and its regulatory effect on the
AC/cAMP/PKA signaling pathway in rats with attention deficit hyperactivity
disorder].
AB - OBJECTIVE: To study the effect of baicalin on synaptosomal adenosine
triphosphatase (ATPase) and lactate dehydrogenase (LDH) and its regulatory effect
on the adenylate cyclase (AC)/cyclic adenosine monophosphate (cAMP)/protein
kinase A (PKA) signaling pathway in rats with attention deficit hyperactivity
disorder (ADHD). METHODS: A total of 40 SHR rats were randomly divided into five
groups: ADHD model, methylphenidate hydrochloride treatment (0.07 mg/mL), and low
dose (3.33 mg/mL), medium-dose (6.67 mg/mL), and high-dose (10 mg/mL) baicalin
treatment (n=8 each). Eight WKY rats were selected as normal control group.
Percoll density gradient centrifugation was used to prepare brain synaptosomes
and an electron microscope was used to observe their structure. Colorimetry was
used to measure the activities of ATPase and LDH in synaptosomes. ELISA was used
to measure the content of AC, cAMP, and PKA. RESULTS: Compared with the normal
control group, the ADHD model group had a significant reduction in the ATPase
activity, a significant increase in the LDH activity, and significant reductions
in the content of AC, cAMP, and PKA (P<0.05). Compared with the ADHD model group,
the methylphenidate hydrochloride group and the medium- and high-dose baicalin
groups had a significant increase in the ATPase activity (P<0.05), a significant
reduction in the LDH activity (P<0.05), and significant increases in the content
of AC, cAMP, and PKA (P<0.05). Compared with the methylphenidate hydrochloride
group, the high-dose baicalin group had significantly greater changes in these
indices (P<0.05). Compared with the low-dose baicalin group, the high-dose
baicalin group had a significant increase in the ATPase activity (P<0.05); the
medium- and high-dose baicalin groups had a significant reduction in the LDH
activity (P<0.05) and significant increases in the content of AC, cAMP, and PKA
(P<0.05). Compared with the medium-dose baicalin group, the high-dose baicalin
group had a significant increase in the ATPase activity (P<0.05). CONCLUSIONS:
Both methylphenidate hydrochloride and baicalin can improve synaptosomal ATPase
and LDH activities in rats with ADHD. The effect of baicalin is dose-dependent,
and high-dose baicalin has a significantly greater effect than methylphenidate
hydrochloride. Baicalin exerts its therapeutic effect possibly by upregulating
the AC/cAMP/PKA signaling pathway.
PMID- 28506354
TI - [Immunoprotective effect of combined pneumococcal endopeptidase O and
pneumococcal surface adhesin A vaccines against Streptococcus pneumoniae
infection].
AB - OBJECTIVE: To investigate the prokaryotic expression of proteins pneumococcal
endopeptidase O (PepO) and pneumococcal surface adhesin A (PsaA) in Streptococcus
pneumoniae and their immunoprotective effect as vaccine candidate proteins.
METHODS: Specific primers of target gene fragments were designed, and then PCR
amplification was performed to establish recombinant plasmids pET28a(+)-pepO and
pET28a(+)-psaA, which were transformed into host cells, Escherichia coli BL21 and
DE3, respectively, to induce expression. Highly purified target proteins PepO and
PsaA were obtained after purification. Mucosal immunization was performed for
BALB/c mice and specific antiserum was prepared. ELISA was used to measure the
antibody titer, and Western blot was used to analyze the specificity of the
antiserum of target proteins. The mice were randomly divided into negative
control group, PepO group, PsaA group, and PepO+PsaA combined immunization group,
with 18 mice in each group. The models of different serotypes of Streptococcus
pneumoniae infection were established to evaluate the immunoprotective effect of
target proteins used alone or in combination. RESULTS: The target proteins PepO
and PsaA were successfully obtained and Western blot demonstrated that the
antiserum of these proteins had good specificity. There was no significant
difference in the titers of IgA in saliva and IgG in serum between the PepO group
and the combined immunization group (P>0.05); however, these two groups had
significantly higher antibody titers than the PsaA group (P<0.05). The PepO,
PsaA, and combined immunization groups had significantly higher protection rates
for mice infected with Streptococcus pneumoniae D39 and CMCC31436 in the nasal
cavity than the negative control group (P<0.05). The PepO and combined
immunization groups had a significantly higher protection rate for mice infected
with Streptococcus pneumoniae D39 than the PsaA group (P<0.05). The results of
colonization experiment showed that compared with the control group, the PepO,
PsaA, and combined immunization groups showed a significant reduction in the
colonization of Streptococcus pneumoniae (CMCC31693 and CMCC31207) in the
nasopharynx and lung (P<0.05). The combined immunization group showed a better
effect on reducing the colonization of CMCC31207 in the lung than the PepO and
PsaA alone groups. CONCLUSIONS: Combined PepO/PsaA vaccines may produce a better
protective effect by mucosal immunization compared with the vaccine used alone in
mice. The combined vaccines can effectively reduce the colonization of
Streptococcus pneumoniae in the nasopharynx and lung. Therefore, such protein
vaccines may have a great potential for research and development.
PMID- 28506355
TI - [Effects of adipose-derived stem cells and non-methylated CpG
oligodeoxynucleotides on peripheral blood CD4+CD25+ regulatory T cells in young
mice with food allergy].
AB - OBJECTIVE: To investigate the effects of adipose-derived stem cells (ADSC) and
non-methylated CpG-oligodeoxynucleotides (CpG-ODN) on the expression of
peripheral blood CD4+CD25+ regulatory T (Treg) cells in young mice with food
allergy, as well as their immune intervention effects. METHODS: A total of 40
female BALB/c mice were randomly divided into control group, allergic group, ADSC
treatment group, and CpG-ODN treatment group, with 10 mice in each group. A mouse
model of food allergy was established by intraperitoneal injection and
intragastric administration of ovalbumin (OVA) for sensitization and challenge.
The mice in the control group were treated with normal saline at the same dose;
the mice in the ADSC treatment group were given intraperitoneal injection of ADSC
(1*106 cells for each mouse) before and after OVA challenge, and those in the CpG
ODN treatment group were given intraperitoneal injection of non-methylated CpG
ODN solution (40 MUg for each mouse) at 1 hour before challenge by gavage. The
allergic symptom scores were determined for each group after model establishment.
ELISA was used to measure the serum level of OVA-IgE. Flow cytometry was used to
measure the percentage of peripheral blood CD4+CD25+ Treg cells. Hematoxylin and
eosin staining was used for the pathological analysis of the jejunum. RESULTS:
The allergic group had significantly higher allergic symptom scores and serum
level of OVA-IgE than the control group (P<0.05). There were no significant
differences in the allergic symptom score and the serum level of OVA-IgE between
the ADSC treatment group and the CpG-ODN treatment group (P>0.05), but these two
groups had significantly lower allergic symptom scores and serum level of OVA-IgE
than the allergic group and significantly higher allergic symptom scores and
serum level of OVA-IgE than the control group (P<0.01). The allergic group had a
significantly lower percentage of peripheral blood CD4+CD25+ Treg cells than the
control group (P<0.05). The ADSC treatment group and the CpG-ODN treatment group
had a significantly higher percentage of peripheral blood CD4+CD25+ Treg cells
than the allergic group (P<0.05); there were no significant differences between
these two groups or between them and the control group (P>0.05). Pathological
results showed structural damage and edema in the jejunal villi, a large number
of eosinophils, and lymphocyte infiltration in the allergic group, while the ADSC
treatment group and the CpG-ODN treatment group had less structural damage and
edema in the jejunal villi, a lower number of eosinophils, and less lymphocyte
infiltration. CONCLUSIONS: ADSC and non-methylated CpG-ODN have a certain effect
in the treatment of food allergy and can increase the percentage of peripheral
blood CD4+CD25+ Treg cells and reduce the level of OVA-IgE. They may be
associated with the induction of immune tolerance and these two treatment have
comparable effects. Detailed mechanisms of action still need further
investigation.
PMID- 28506357
TI - [Research advances in the association between maternal intake of methyl donor
nutrients during pregnancy and DNA methylation in offspring].
AB - Maternal nutrition during pregnancy plays a vital role in the health of the
offspring. Methyl donor nutrients, including folate, vitamin B12, choline,
betaine, and methionine, directly affect DNA methylation and are closely
associated with the health of the offspring. As an important part of epigenetics,
DNA methylation plays an important role in the maintenance of normal cellular
function, gene expression regulation, and embryonic development. Recent studies
have shown that maternal nutrition may have a long-lasting effect on the health
of the offspring via the changes in genomic DNA and/or methylation level in the
promoter region in specific genes. Therefore, this review article focuses on the
effect of maternal intake of methyl donor nutrients during pregnancy on DNA
methylation, in order to explore the effect of the changed methylation status on
the health of the offspring at the molecular level.
PMID- 28506356
TI - [Research advances in nutritional assessment methods in children with chronic
liver diseases].
AB - Malnutrition is commonly seen in children with chronic liver diseases, and there
are interactions between them. Chronic liver diseases can cause malnutrition and
this can affect the prognosis of children with chronic liver diseases. Due to the
complexity of nutritional assessment in children with chronic liver diseases,
there are still no unified standards for the diagnosis of malnutrition. Early
identification of malnutrition and related intervention helps to improve the
prognosis of children with chronic liver diseases. This article reviews the
features of nutrition in children with chronic liver diseases and related
nutritional assessment methods.
PMID- 28506358
TI - [Research advances in noninvasive high-frequency oscillatory ventilation in
neonates].
AB - Noninvasive ventilation is an important respiratory management technique for the
treatment of mild or moderate respiratory failure in the neonatal intensive care
unit. Its reasonable application can effectively avoid the use of invasive
ventilation and related complications. Recent studies have found that noninvasive
high-frequency oscillatory ventilation has the advantages of both nasal
continuous positive airway pressure and high-frequency ventilation and can
rapidly improve oxygenation, effectively remove carbon dioxide, and improve
respiratory failure. Therefore, it is considered a new and effective noninvasive
ventilation mode. There are many studies on the rational use, efficacy, and
safety of noninvasive high-frequency oscillatory ventilation in neonates around
the world. This article reviews the advances in the clinical studies on
noninvasive high-frequency oscillatory ventilation in neonates.
PMID- 28506359
TI - Humans treat unreliable filled-in percepts as more real than veridical ones.
AB - Humans often evaluate sensory signals according to their reliability for optimal
decision-making. However, how do we evaluate percepts generated in the absence of
direct input that are, therefore, completely unreliable? Here, we utilize the
phenomenon of filling-in occurring at the physiological blind-spots to compare
partially inferred and veridical percepts. Subjects chose between stimuli that
elicit filling-in, and perceptually equivalent ones presented outside the blind
spots, looking for a Gabor stimulus without a small orthogonal inset. In
ambiguous conditions, when the stimuli were physically identical and the inset
was absent in both, subjects behaved opposite to optimal, preferring the blind
spot stimulus as the better example of a collinear stimulus, even though no
relevant veridical information was available. Thus, a percept that is partially
inferred is paradoxically considered more reliable than a percept based on
external input. In other words: Humans treat filled-in inferred percepts as more
real than veridical ones.
PMID- 28506361
TI - IgG4-related Disease and the Liver.
AB - Pathologists are likely to encounter IgG4-related disease in several organ
systems. This article focuses on helping pathologists diagnose IgG4-related
disease in the hepatobiliary system. Missing the diagnosis can result in
unnecessary organ damage and/or unnecessary surgical and cancer therapy. In the
liver, tumefactive lesion(s) involving the bile ducts with storiform fibrosis and
an IgG4-enriched lymphoplasmacytic infiltrate are highly concerning for IgG4
related disease. The recent identification of oligoclonal populations of T cells
and B cells in IgG4-related disease may lead to molecular tests, new
therapeutics, and a greater mechanistic understanding of the disease.
PMID- 28506362
TI - Current Concepts in Pediatric Nonalcoholic Fatty Liver Disease.
AB - Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of disease. Its
increasing prevalence is a direct result of historically high rates of obesity.
Hepatocyte lipid accumulation is the first step in a cascade of metabolic and
inflammatory events thought to precipitate NAFLD. Histologic findings provide
insight into these events. Lifestyle modification remains the primary therapy in
children. Current recommendations include vitamin E treatment in those with
biopsy-proven NASH. Trials of novel drugs are ongoing in adults. As
efficacy/safety are established, these therapies may be tenable for use in
children. At the current time, biopsy-driven histology endpoints are necessary to
establish whether future therapies can improve pediatric or adult-type NASH in
children.
PMID- 28506363
TI - Contemporary Evaluation of the Pediatric Liver Biopsy.
AB - Liver disease in the neonate, infant, child, and adolescent may manifest
differently depending on the type of disorder. These disorders show marked
overlap clinically and on light microscopy. Histology and ultrastructural
examination are used in tandem for the diagnosis of most disorders. A final
diagnosis or interpretation of the pediatric liver biopsy depends on appropriate
and adequate clinical history, laboratory test results, biochemical assays, and
molecular analyses, as indicated by the light microscopic and ultrastructural
examination.
PMID- 28506360
TI - Plasmodium P36 determines host cell receptor usage during sporozoite invasion.
AB - Plasmodium sporozoites, the mosquito-transmitted forms of the malaria parasite,
first infect the liver for an initial round of replication before the emergence
of pathogenic blood stages. Sporozoites represent attractive targets for
antimalarial preventive strategies, yet the mechanisms of parasite entry into
hepatocytes remain poorly understood. Here we show that the two main species
causing malaria in humans, Plasmodium falciparum and Plasmodium vivax, rely on
two distinct host cell surface proteins, CD81 and the Scavenger Receptor BI (SR
BI), respectively, to infect hepatocytes. By contrast, CD81 and SR-BI fulfil
redundant functions during infection by the rodent parasite P. berghei. Genetic
analysis of sporozoite factors reveals the 6-cysteine domain protein P36 as a
major parasite determinant of host cell receptor usage. Our data provide
molecular insights into the invasion pathways used by different malaria parasites
to infect hepatocytes, and establish a functional link between a sporozoite
putative ligand and host cell receptors.
PMID- 28506364
TI - Hepatocellular Adenomas: Morphology and Genomics.
AB - Hepatocellular adenomas (HCAs) are rare benign tumors. This single entity has
been split into 3 subtypes corresponding to specific mutations: HNF1alpha
inactivated HCA; inflammatory HCA related to different mutations, all leading to
activation of STAT3 pathway; and beta-catenin-activated HCA related to CTNNB1
mutations. The risk of malignant transformation depends on the level of beta
catenin activation, reported mainly for exon 3, including S45. It is possible
using specific immunohistochemical markers to identify the 3 different HCA
subtypes and the level of beta-catenin activation. Fewer than 10% of HCAs remain
unclassified.
PMID- 28506366
TI - Antibody-Mediated Rejection After Liver Transplant.
AB - Antibody-mediated rejection (AMR) in liver transplants is a field in its infancy
compared with its allograft cohorts of the kidney and lung. Acute AMR is
diagnosed based on specific clinical and histopathologic criteria: serum donor
specific antibodies, C4d staining, histopathologic findings on liver biopsy, and
exclusion of other entities. In contrast, the histologic features of chronic AMR
are not as specific and it is a more challenging diagnosis to make. Treatments of
acute and chronic AMR include some combination of steroids, immune-modulating
agents, intravenous immunoglobulin, plasmapheresis, and proteasome inhibitors.
PMID- 28506365
TI - Drug-induced Liver Injury: The Hepatic Pathologist's Approach.
AB - The evaluation of liver biopsies in suspected drug-induced liver injury (DILI)
can be complex. The biopsy may be approached systematically, by identification of
histologic lesions and then identification of the overall pattern of injury.
Potential DILI must be separated from concomitant non-DILI liver disease. The
findings can be analyzed with respect to the various prescription and
nonprescription medications and dietary supplements under suspicion to provide a
complete interpretation of the findings. The pathologic findings, the histologic
differential diagnosis, and expert interpretation are part of a complete biopsy
assessment and provide information that is of greatest value in patient
management.
PMID- 28506367
TI - Immunohistochemistry in the Diagnosis of Hepatocellular Carcinoma.
AB - Hepatocellular carcinoma (HCC) can be difficult to distinguish from its mimics,
including metastatic tumor, benign hepatocellular lesion, and high-grade
dysplastic nodule, especially when limited biopsy material is available. Hence,
the judicious use of immunohistochemical stains is necessary to establish a
correct diagnosis. This article describes advantages and disadvantages of
immunohistochemical markers that are most commonly used to distinguish between
these lesions. Diagnostic workup of malignant liver mass (HCC and its histologic
variants vs metastatic tumor) as well as well-differentiated hepatocellular
lesion (well-differentiated HCC vs focal nodular hyperplasia vs hepatocellular
adenoma) is also discussed.
PMID- 28506368
TI - Human Immunodeficiency Virus Infection, Antiretroviral Therapy, and Liver
Pathology.
AB - The improvement in antiretroviral therapy has significantly impacted the lives of
people living with human immunodeficiency virus (HIV). In high-income countries,
HIV deaths are predominated by liver disease consequent to viral hepatitis
coinfection, alcohol, and nonalcoholic fatty liver disease. Published liver
pathology findings have shifted from being predominated by opportunistic
infections to the metabolic effects of HIV and antiretroviral therapy as well as
drug-induced liver injuries. Differences remain between high-income and low
income countries, where opportunistic infections and immune reconstitution
syndromes, dominate findings.
PMID- 28506369
TI - Autoimmune Hepatitis Overlap Syndromes and Liver Pathology.
AB - Autoimmune hepatitis (AIH) may have an atypical serum alkaline phosphatase
elevation, antimitochondrial antibodies, histologic features of bile duct
injury/loss, or cholangiographic findings of focal biliary strictures and
dilations. These manifestations characterize the overlap syndromes. Patients can
be classified as having AIH with features of primary biliary cholangitis, primary
sclerosing cholangitis, or a cholestatic syndrome. The gold standard of diagnosis
is clinical judgment. Histologic evaluation is a major diagnostic component.
Treatment is based on algorithms; outcomes vary depending on the predominant
disease component. Combination therapy has been the principal recommendation.
PMID- 28506370
TI - Morphologic Subtypes of Hepatocellular Carcinoma.
AB - Hepatocellular carcinomas can be further divided into distinct subtypes that
provide important clinical information and biological insights. These subtypes
are distinct from growth patterns and are on based on morphologic and molecular
findings. There are 12 reasonably well-defined subtypes as well as 6 provisional
subtypes, together making up 35% of all hepatocellular carcinomas. These subtypes
are discussed, with an emphasis on their definitions and the key morphologic
findings.
PMID- 28506371
TI - Hepatitis E Virus and the Liver: Clinical Settings and Liver Pathology.
AB - Infection with hepatitis E virus (HEV) is a leading cause of acute hepatitis
worldwide, now increasingly recognized also in nonendemic regions. Clinical
manifestation of hepatitis E includes mostly asymptomatic/subclinical
presentations or acute, self-limiting hepatitis, but also potentially fatal liver
failure or chronic hepatitis in immunocompromised individuals. Accordingly,
hepatitis E histolpathologic patterns range from an unremarkable histology over
acute (cholestatic) hepatitis with variable degree of necrosis to chronic
hepatitis with fibrosis. Awareness of hepatitis E and its differential diagnoses,
knowledge of its clinico-pathologic manifestations and familiarity with its
diagnostic tools will enable clinicians and pathologists to competently make this
diagnosis.
PMID- 28506372
TI - Hepatic Progenitor Cells: An Update.
AB - Liver regeneration is a fascinating and complex process with many medical
implications. An important component of this regenerative process is the hepatic
progenitor cell (HPC). These appealing cells are able to participate in the
renewal of hepatocytes and cholangiocytes when the normal homeostatic
regeneration is exhausted. Moreover, the HPC niche is of vital importance toward
the activation, differentiation, and proliferation of the HPC. This niche
provides a rich microenvironment for the regulation of the HPC, thanks to the
intercellular secretion of molecules. New findings indicate that the regenerative
possibilities in the liver could provide a diverse basis for therapeutic targets.
PMID- 28506373
TI - Heart Disease and the Liver: Pathologic Evaluation.
AB - Liver injury due to acute and chronic heart failure has long been recognized.
This article discusses the concepts of acute cardiogenic liver injury (ACLI) and
cardiac or congestive hepatopathy (CH) along with their clinical manifestations
and sequelae. Histologically, ACLI manifests as centrilobular hepatocellular
necrosis, whereas CH is associated with centrilobular hepatocyte atrophy, dilated
sinusoids, and perisinusoidal fibrosis, progressing to bridging fibrosis and
ultimately cirrhosis. ACLI is associated with marked increases in
aminotransferase levels, whereas CH is associated with a cholestatic pattern of
laboratory tests. Certain cardiac medications have also been implicated as a
cause of liver fibrosis.
PMID- 28506374
TI - Liver Pathology.
PMID- 28506375
TI - Erratum.
PMID- 28506376
TI - Community-based pharmacy residents: Engaged at the intersection of health and
medication needs.
PMID- 28506377
TI - Beyond the PGY-1 community pharmacy residency: Characterizing career pathways of
residency graduates.
AB - OBJECTIVE: To characterize positions obtained upon graduation from Community
Pharmacy Residency Programs (CPRPs). DESIGN: Descriptive nonexperimental study;
online cross-sectional survey. SETTING: United States, February to April 2016.
PARTICIPANTS: One hundred thirty-three community pharmacy residency program
alumni. INTERVENTION: CPRP alumni identified by past program directors were
surveyed using 3 contact attempts. MAIN OUTCOME MEASURES: Descriptive measures of
demographics and information regarding post-CPRP employment including sex,
region, degree status, number of positions offered, and further specialization
were determined. Skills developed during CPRPs, such as research, teaching,
management, advocacy, and clinical service provision during employment, were
reported. RESULTS: E-mails were sent to 216 potential participants, and 133
useable survey responses were gathered from CPRP alumni. When asked how many
positions were offered upon residency graduation, 57% were offered 2 positions
and 26% were offered 3 positions. Of those employed, 50% of respondents indicated
employment at the practice site at which they completed their CPRP. The amount of
time spent on traditional dispensing decreased from the initial post-residency
position to the current position. The time CPRP graduates spent in roles
involving research, management, and advocacy activities in their current position
was increased. CONCLUSION: Graduates of CPRPs spend approximately 34% of their
time dispensing, which is less than the national average reported by the National
Pharmacist Workforce Survey. A contributing factor to the expansion of CPRPs
largely depends on the ability of employment opportunities that embrace the value
this unique skill set brings. CPRPs foster clinical innovation and leadership in
the community setting, thus creating additional opportunities for pharmacists to
demonstrate their value to the health care system.
PMID- 28506378
TI - Pharmacist-to-prescriber intervention to close therapeutic gaps for statin use in
patients with diabetes: A randomized controlled trial.
AB - OBJECTIVE: To assess the effect of a community pharmacist-led intervention on the
proportion of patients with diabetes placed on statin therapy. DESIGN: The
Pharmacy Quality Alliance endorsed a performance measure, Statin Use in Persons
with Diabetes, which evaluates the percentage of patients aged 40-75 years who
were dispensed a medication for diabetes and also received a statin medication.
SETTING: This new measure has been implemented within the Electronic Quality
Improvement Platform for Plans and Pharmacies (EQuIPP) dashboard. PARTICIPANTS:
In this randomized controlled study, eligible patients identified in EQuIPP are
those who received medications from a large chain community pharmacy in North
Carolina, are 40-75 years, had >=2 prescription fills of a diabetes medication,
and were not receiving statin therapy. INTERVENTION: The control group received
no intervention. Primary care prescribers of patients in the intervention group
were contacted by phone and fax to obtain a prescription for an appropriate
statin. MAIN OUTCOME MEASURES: The primary outcome was the proportion of patients
in each group who were dispensed a statin, calculated using Fisher exact test.
Sub-analyses were performed to control for patient age, sex, and insurance type.
RESULTS: The number of statins prescribed was statistically significant between
intervention group (n = 221) versus control group (n = 199) with 46 statins
versus 17 statins, respectively (P <0.001). The number of statins dispensed was
also statistically significant between groups with 34 statins in the intervention
group versus 15 statins in the control group (P = 0.015). The fourth most common
(9.2%) reason prescribers rejected statin therapy initiation was "Patient has
normal cholesterol" and this caused the greatest amount of discussion between
pharmacist and prescriber. CONCLUSION: Through a brief pharmacist-to-provider
intervention, a significant gap closure in statin therapy was seen in patients
with diabetes. There is an opportunity for pharmacies, health plans, and
prescribers to utilize the community pharmacist in achieving quality, evidence
based patient care.
PMID- 28506379
TI - Pharmacist-initiated hepatitis C virus screening in a community pharmacy to
increase awareness and link to care at the medical center.
AB - OBJECTIVE: To describe the design and implementation of a pharmacist-led
hepatitis C virus (HCV) screening and education program in a community pharmacy
with a protocol for linkage to care at the affiliated hepatology clinic for
patients born between 1945 and 1965. SETTING: Outpatient pharmacy affiliated with
the University of Illinois Hospital and Health Sciences System. PRACTICE
DESCRIPTION: The community pharmacist resident conducted the HCV screening at the
health system-based community pharmacy. PRACTICE INNOVATION: Community
pharmacists provided patients with HCV screening and education while patients
waited for their prescriptions to be ready or upon appointment. Patients were
given a questionnaire before and after HCV education to assess the impact of
pharmacist-provided education on patient knowledge. A protocol was developed to
link patients with a positive HCV antibody test result to care with a
hepatologist for confirmatory testing at a follow-up appointment at the medical
center. EVALUATION: Investigators assessed the feasibility of providing the
screening and education, recorded the number of patients screened, and recorded
the differences in the questionnaire responses before and after education.
RESULTS: Pharmacist-led HCV screening services were implemented successfully at
the community pharmacy. All patients had a negative antibody result; therefore,
linkage to care at the medical center, although available, was not necessary. The
self-reported posttest HCV knowledge scores were significantly higher than
pretest scores. CONCLUSION: This article outlines the methodology for providing a
multidisciplinary HCV screening, education, and referral program in a community
pharmacy affiliated with a medical center. Pharmacist-initiated HCV screening in
a community pharmacy can assist with identifying patients at risk for HCV
infection and provide patients with linkage to care in the health system. This
report may encourage community pharmacists to conduct future prospective trials
to evaluate clinical and economic outcomes of community-based HCV screenings.
PMID- 28506380
TI - Use of communication tool within electronic medical record to improve primary
nonadherence.
AB - OBJECTIVES: The primary objective of this study was to determine if an online
reminder decreased the rate of primary nonadherence for antihypertensive
medications in patients seen in 2 primary care clinics in Omaha, NE. The
secondary objectives were to determine if patients receiving the intervention
achieved lower blood pressure values at follow-up visits and to determine if the
intervention decreased the number of days between prescribing and prescription
pick-up. METHODS: A report was generated in an electronic health record to
identify patients prescribed a new antihypertensive medication from a physician
at one of the primary care clinics. Patients that failed to pick up this new
prescription from the pharmacy within 7 days were sent an electronic reminder via
an online patient portal. A baseline comparator group was created with the use of
retrospective chart reviews for the 6 months before prospective data collection.
Primary nonadherence rate and blood pressure values at follow-up visits were
compared between the prospective and baseline comparator groups. RESULTS: The
primary nonadherence rate decreased from 65.5% to 22.2% when comparing the
baseline and prospective groups, respectively. The mean days to prescription pick
up decreased from 24.5 to 12.56 in the baseline and prospective groups. The
prospective group showed a larger decrease in systolic blood pressure (17.33 mm
Hg vs. 0.75 mm Hg) and diastolic blood pressure (6.56 mm Hg vs. 2.25 mm Hg)
compared with the baseline group. CONCLUSION: An online reminder through the
electronic medical record appears to improve patient primary nonadherence, number
of days between prescribing and prescription pick-up, and blood pressure
measurements at follow-up visits. This research shows that an online reminder may
be a valuable tool to improve patient primary adherence and health outcomes.
Further research is needed with the use of a larger sample population to support
any hypotheses about the effectiveness of the intervention.
PMID- 28506382
TI - A simplified pathway to proprotein convertase subtilisin/kexin type 9 inhibitor
prior authorization approval: A lipid clinic experience.
PMID- 28506383
TI - Can iPCSK9-induced hypocholesterolemia starve cancer cells?
PMID- 28506381
TI - Description of drug therapy problem resolution in a statewide care management
program.
AB - OBJECTIVE: To describe drug therapy problem (DTP) resolution as part of a
statewide, team-based care management program. METHODS: This was a retrospective,
observational study of DTPs documented between March 1 and August 31, 2015. Data
were retrieved from a Web-based platform 5 months after the observation period.
DTPs were placed into groups based on the credentials of the person who
documented the DTP. Next, they were identified as being documented in a
transitional or nontransitional care setting. DTPs were further classified into 1
of 3 categories: medication adherence, discrepancy, or optimization. Lastly, DTP
resolution was assessed. Results were analyzed using descriptive statistics.
RESULTS: During the 6-month study period, 135,100 DTPs were documented, with 99%
(n = 133,847) being documented by social work care managers, nurse care managers,
and pharmacy staff personnel. Pharmacy staff personnel documented the majority of
DTPs (51.5%), and the majority of DTPs (55%) were identified in the transitional
care setting. Nurse care managers resolved more discrepancy DTPs (59.3%), whereas
pharmacy staff personnel resolved more optimization DTPs (47.2%). Social work
care managers resolved more medication adherence DTPs (68.6%). CONCLUSIONS:
Pharmacy staff personnel primarily identified and resolved opportunities to
optimize medication use, whereas nurse care managers primarily identified and
resolved medication discrepancies. Social work care managers primarily identified
and resolved problems related to medication adherence. When each member of the
interdisciplinary care team functioned at the top of their license, all types of
DTPs were effectively identified and resolved.
PMID- 28506384
TI - Managing the challenging homozygous familial hypercholesterolemia patient:
Academic insights and practical approaches for a severe dyslipidemia, a National
Lipid Association Masters Summit.
AB - The following article represents material presented and discussed at a symposium
hosted by the National Lipid Association hosted entitled "Managing the
Challenging Homozygous Familial Hypercholesterolemia Patient-Academic Insights
and Practical Approaches for a Severe Dyslipidemia" on November 7, 2015 in
Orlando, FL. Presenters included G.K.H., A.C.G, and P.M.M. The diagnosis and
genetic causes of extremely high low-density lipoprotein (LDL) cholesterol, which
has become known as homozygous familial hypercholesterolemia, were discussed.
This disorder in adults manifest often by LDL cholesterol in excess of 500 occurs
in several populations with a prevalence of 1 in 300,000. In more sequestered
areas, the frequency may be much greater due to founder effects of specific
settlers carrying the responsible alleles. Although the great majority of these
patients have a variant sequences in the LDL receptor gene, variants in the
apolipoprotein B, proprotein convertase subtilisin kexin type 9, or LDL receptor
adaptor protein gene loci can also be causative. Some individuals have additional
genetic abnormalities, which have not been fully revealed. In most studies, the
diagnosis has depended on predefined clinical findings in association with the
very elevated LDL cholesterol. Standard lipid-lowering drugs such as statins,
ezetimibe, or bile acid-binding resins are usually only partially beneficial and
leave the patients at high risk. Lipoprotein apheresis has been a more effective
therapy and is a mainstay in treatment of many patients. New therapies such as
mipomersen and lomitapide have reduced LDL dramatically in some but are often
ineffective in others. Inhibitors of proprotein convertase subtilisin kexin type
9 can reduce LDL dramatically but in those with null genes for the LDL receptor,
they are also ineffective. The availability of this battery of drugs has markedly
improved the potential of pharmacotherapy to control LDL values and prolong the
life of these patients.
PMID- 28506385
TI - Hydrophilic vs lipophilic statins in coronary artery disease: A meta-analysis of
randomized controlled trials.
AB - INTRODUCTION: Some available experimental studies have reported that hydrophilic
statins might have advantages compared with lipophilic statins in patients with
coronary artery disease (CAD). Therefore, we performed a meta-analysis of
randomized controlled trials (RCTs) investigating the potential differences of
lipophilic and hydrophilic statins in patients with CAD. METHODS: We
systematically searched selected electronic databases up to September 2016 to
select RCTs, which compared clinical outcomes of hydrophilic vs lipophilic
statins. Primary endpoints were cardiovascular (CV) events: major adverse cardiac
events, myocardial infarction, cardiac revascularization, stroke, CV death, CV
hospitalization, and all-cause mortality. Secondary endpoints were safety
parameters: drug discontinuation, statin-associated muscle symptoms and alanine
aminotransferase level increase. RESULTS: A total of 11,697 patients from 11
RCTs, randomly allocated to lipophilic (n = 5736) or hydrophilic statins (n =
5961), with a mean follow-up 14 months, were included in the meta-analysis. In
comparison with hydrophilic, the lipophilic statins showed similar risk reduction
for major adverse cardiac events (relative risk = 0.969, 95% confidence interval
[CI], 0.835-1.125, P = .682), myocardial infarction (0.880, 95% CI: 0.731-1.058,
P = .174), CV death (0.757, 95% CI: 0.486-1.180, P = .219), and all-cause
mortality (0.797, 95% CI: 0.590-1.075, P = .137), as well as cardiac
revascularization, stroke, drug discontinuation, and statin-associated muscle
symptoms. CV hospitalization was lower (0.789, 95% CI: 0.643-0.969, P = .024) and
alanine aminotransferase elevation was higher (2.689, 95% CI: 1.841-3.954, P <=
.001) in lipophilic than in hydrophilic-treated patients. CONCLUSIONS: In
conclusion, similarity between hydrophilic and lipophilic statins holds between
various clinical CAD settings.
PMID- 28506386
TI - Serum triglyceride, high-density lipoprotein cholesterol, apolipoprotein B, and
coronary heart disease in a Chinese population undergoing coronary angiography.
AB - BACKGROUND: Increased serum triglyceride and apolipoprotein B (apoB) levels and
decreased high-density lipoprotein cholesterol (HDL-C) levels are risk factors
for cardiovascular diseases. The major types of dyslipidemia in Chinese
population are hypertriglyceridemia and low HDL-C. OBJECTIVE: This study aimed to
evaluate the effect of HDL-C, triglyceride, and apoB levels on the risk of
coronary heart disease (CHD) in a Chinese population undergoing coronary
angiography. METHODS: This was a cross-sectional study. A total of 1941
consecutive patients who were referred to coronary angiography for the evaluation
of suspected CHD were recruited. Lipid parameters were measured after an
overnight fast. Patients were diagnosed with CHD and without CHD based on the
findings of the coronary angiography. RESULTS: There were 1363 angiography
confirmed CHD patients and 578 non-CHD patients. In nonstatin users, the major
types of dyslipidemia were hypertriglyceridemia combined with low HDL-C, isolated
low HDL-C, and isolated hypertriglyceridemia, accounting for 21.60%, 19.70%, and
14.99%, respectively. In statin users, a low to moderate-intensity statin was
effective in lowering low-density lipoprotein cholesterol (LDL-C). The proportion
of reaching an LDL-C goal <2.6 mmol/L and <1.8 mmol/L in statin users was 83.20%
and 55.19%, respectively. In nonstatin users, the triglyceride and apoB levels
were higher and the HDL-C levels were lower in CHD patients compared with non-CHD
patients after the adjustment of age, sex, body mass index, diabetes, smoking,
and alcohol drinking (P = .002, .007, and .005, respectively). After adjusting
for age, sex, body mass index, diabetes, hypertension, smoking and alcohol
drinking, the quartiles of triglyceride, HDL-C, and apoB were associated with CHD
(P for trend = .001, .005, and .003, respectively). CONCLUSION: Serum
triglyceride, HDL-C, and apoB levels were independently associated with CHD in a
Chinese population undergoing coronary angiography with a relatively low level of
LDL-C and a high prevalence of hypertriglyceridemia and low HDL-C.
PMID- 28506387
TI - Effects of atorvastatin treatment on left ventricular diastolic function in
peritoneal dialysis patients-The ALEVENT clinical trial.
AB - BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is common among
patients undergoing peritoneal dialysis (PD). Increased levels of inflammatory
biomarkers, such as high-sensitivity C-reactive protein, predict the development
of LVDD. OBJECTIVES: We hypothesized that PD patients with elevated high
sensitivity C-reactive protein levels might benefit from statin treatment for
LVDD and designed a randomized clinical trial to prove the hypothesis. METHODS:
We screened 213 PD patients and randomly assigned 32 men and women with low
density lipoprotein cholesterol levels <130 mg/dL, high-sensitivity C-reactive
protein levels of >=1.5 mg/L, and LVDD, diagnosed by conventional and tissue
Doppler imaging (TDI) echocardiography, to treatment with atorvastatin, 40 mg
daily, or without. The primary end points were changes in TDI diastolic
parameters or global strain imaging diastolic parameters. RESULTS: Atorvastatin
reduced low-density lipoprotein cholesterol levels by 43% and high-sensitivity C
reactive protein levels by 45% (both P < .001). Follow-up TDI showed significant
improvement of early mitral flow velocities divided by early diastolic peak
velocities of the mitral annulus at the medial and lateral site (Nominal change
for E/Emedial: -5.01 +/- 6.36 vs 1.80 +/- 6.59 for atorvastatin and control,
respectively, P = .02). There was also a significant improvement in global strain
imaging after atorvastatin treatment (global strain rate, -17.12 +/- 1.42 vs
14.61 +/- 1.78 for atorvastatin and control, respectively, P = .002 and E/SRIVR,
462.35 +/- 110.54 vs 634.09 +/- 116.81, P = .003). CONCLUSIONS: In this trial of
PD patients without hyperlipidemia but with elevated high-sensitivity C-reactive
protein levels and LVDD, atorvastatin significantly improved cardiac diastolic
function (ClinicalTrials.gov number, NCT01503671).
PMID- 28506389
TI - Proprotein convertase subtilisin/kexin 9 inhibition in patients with familial
hypercholesterolemia: Initial clinical experience.
AB - BACKGROUND: Despite optimal lipid-lowering therapy, a minority of patients with
familial hypercholesterolemia (FH) reach low-density lipoprotein cholesterol (LDL
c) target goals. In randomized trials, proprotein convertase subtilisin/kexin 9
(PCSK9) inhibitors led to impressive LDL-c reductions and a favorable safety
profile. However, data about the efficacy and safety outside clinical trials are
not available yet. OBJECTIVE: The purpose of the study is to describe efficacy
and side effects of PCSK9 inhibitors in FH patients in clinical practice.
METHODS: Registry of all consecutive FH patients who started with a PCSK9
inhibitor at a lipid clinic of a university hospital. RESULTS: We analyzed 83 FH
patients (79 heterozygous FH [heFH]-65 with a genetically confirmed heFH and 14
with clinical heFH-and 4 homozygous FH [hoFH]), with a mean age of 55.1 +/- 11.6
years. Treatment with a PCSK9 inhibitor resulted in an additional reduction of
55% +/- 21% in mean LDL-c levels. Patients with heFH had more LDL-c decrease than
those with hoFH (56% vs 38%). Patients using ezetimibe monotherapy because of
statin intolerance (n = 24, 29%) had less LDL-c decrease compared with patients
who concurrently used statin therapy (47% and 58%, P = .03). Side effects of
PCSK9 inhibitors were reported by 32 patients (39%). Flu-like symptoms (n = 12)
and injection site reactions (n = 11) were most frequent. Seven patients (8%)
discontinued treatment, 5 because of side effects and 2 because of nonresponse.
CONCLUSION: Our initial experience of PCSK9 inhibition in FH patients in a
clinical setting showed comparable reduction in LDL-c levels but more side
effects compared with clinical trials.
PMID- 28506388
TI - Discordant response of low-density lipoprotein cholesterol and lipoprotein(a)
levels to monoclonal antibodies targeting proprotein convertase subtilisin/kexin
type 9.
AB - BACKGROUND: Clinical trials testing proprotein convertase subtilisin/kexin type 9
inhibitors (PCSK9i) have demonstrated an unanticipated but significant
lipoprotein (a) (Lp(a))-lowering effect, on the order of 25% to 30%. Although the
50% to 60% reduction in low-density lipoprotein (LDL)-cholesterol (LDL-C)
achieved by PCSK9i is mediated through its effect on LDL receptor (LDLR)
preservation, the mechanism for Lp(a) lowering is unknown. OBJECTIVE: We sought
to characterize the degree of concordance between LDL-C and Lp(a) lowering
because of PCSK9i in a standard of care patient cohort. METHODS: Participants
were selected from our Center for Preventive Cardiology, an outpatient referral
center in a tertiary academic medical center. Subjects were included in this
study if they had (1) at least 1 measurement of LDL-C and Lp(a) before and after
initiation of the PCSK9i; (2) baseline Lp(a) > 10 mg/dL; and (3) continued
adherence to PCSK9i therapy. They were excluded if (1) they were undergoing LDL
apheresis; (2) pre- or post-PCSK9i LDL-C or Lp(a) laboratory values were
censored; or (3) subjects discontinued other lipid-modifying therapies. In total,
103 subjects were identified as taking a PCSK9i and 26 met all inclusion and
exclusion criteria. Concordant response to therapy was defined as an LDL-C
reduction >35% and an Lp(a) reduction >10%. RESULTS: The cohort consisted of 26
subjects (15 females, 11 males, mean age 63 +/- 12 years). Baseline mean LDL-C
and median Lp(a) levels were 167.4 +/- 72 mg/dL and 81 mg/dL (interquartile range
38-136 mg/dL), respectively. The average percent reductions in LDL-C and Lp(a)
were 52.8% (47.0-58.6) and 20.2% (12.2-28.1). The correlation between %LDL and
%Lp(a) reduction was moderate, with a Spearman's correlation of 0.56 (P < .01).
All subjects except for 1 had a protocol-appropriate LDL-C response to therapy.
However, only 16 of the 26 (62%; 95% confidence interval 41%-82%) subjects had a
protocol-concordant Lp(a) response. Although some subjects demonstrated
negligible Lp(a) reduction associated with PCSK9i, there were some whose Lp(a)
decreased as much as 60%. CONCLUSIONS: In this standard-of-care setting, we
demonstrate moderate correlation but large discordance (~40%) in these 2 lipid
fractions in response to PCSK9i. The results suggest that pathways beyond the
LDLR are responsible for Lp(a) lowering and indicate that PCSK9i have the
potential to significantly lower Lp(a) in select patients, although confirmation
in larger multicenter studies is required.
PMID- 28506391
TI - Lipid profile, changes in laboratory prescriptions are necessary.
PMID- 28506390
TI - Assessment of pharmacokinetic interaction between omega-3 carboxylic acids and
the statins rosuvastatin and simvastatin: Results of 2 phase I studies in healthy
volunteers.
AB - BACKGROUND: Omega-3 carboxylic acids (OM3-CA) can lower triglyceride levels. OM3
CA is often prescribed concomitantly with a 3-hydroxy-3-methylglutaryl coenzyme A
reductase inhibitor (statin). OBJECTIVE: The aim of the article was to assess the
potential for pharmacokinetic interaction between OM3-CA and the statins
rosuvastatin and simvastatin. METHODS: Data from 2 phase I studies (ECLIPSE III
and OM-EPA-007 [NCT01486433]) were analyzed. In ECLIPSE III, 59 participants
received OM3-CA 4 g once daily for 13 days, with rosuvastatin 40 mg (single dose)
co-administered with the 11th dose. In OM-EPA-007, 52 participants received
simvastatin 40 mg plus acetylsalicylic acid 81 mg daily for 14 days, with or
without OM3-CA. Lack of a drug-drug interaction was declared if the 90%
confidence interval (CI) of the geometric least-squares mean ratio of
pharmacokinetic parameters was in the range 80% to 125%. RESULTS: For
rosuvastatin, values for the geometric mean ratio (90% CI) with:without OM3-CA
were 86.38% (80.68-92.48), 90.50% (85.99-95.25), and 89.01% (84.30-93.98),
respectively, for maximum plasma concentration (Cmax), area under the
concentration-time curve up to last measurable concentration (AUC0-t) and
extrapolated to infinity (AUC0-inf). Co-administration with a single dose of
rosuvastatin did not affect the multiple-dose pharmacokinetics of constituent OM3
CA fatty acids eicosapentaenoic acid and docosahexaenoic acid. For simvastatin,
values for steady state geometric mean ratio (90% CI) with:without OM3-CA were
91.61% (82.82-101.33) and 87.47% (80.19-95.41), respectively, for Cmax and AUC0
t. No deaths or serious adverse events occurred in either trial. CONCLUSION: OM3
CA can be administered with either rosuvastatin or simvastatin without affecting
the pharmacokinetics of these statins.
PMID- 28506392
TI - Lipid profile, the world needs to change.
PMID- 28506394
TI - Iron: Its complicated.
PMID- 28506393
TI - Partial rescue of neuropathology in the murine model of PKU following
administration of recombinant phenylalanine ammonia lyase (pegvaliase).
AB - Pegylated recombinant phenylalanine ammonia lyase (pegvaliase) is an enzyme
substitution therapy being evaluated for the treatment of phenylketonuria (PKU).
PKU is characterized by elevated plasma phenylalanine, which is thought to lead
to a deficiency in monoamine neurotransmitters and ultimately, neurocognitive
dysfunction. A natural history evaluation in a mouse model of PKU demonstrated a
profound decrease in tyrosine hydroxylase (TH) immunoreactivity in several brain
regions, beginning at 4weeks of age. Following treatment with pegvaliase, the
number of TH positive neurons was increased in several brain regions compared to
placebo treated ENU2 mice.
PMID- 28506395
TI - An enhanced appreciation of cultural competency: Applying knowledge at home and
abroad.
PMID- 28506396
TI - An enhanced appreciation of cultural competency: Get off your island!
PMID- 28506397
TI - An enhanced appreciation of cultural competency: Developing culturally competent
practitioners.
PMID- 28506398
TI - Integration of pharmacists into patient-centered medical homes in federally
qualified health centers in Texas.
AB - OBJECTIVES: To describe the integration and implementation of pharmacy services
in patient-centered medical homes (PCMHs) as adopted by federally qualified
health centers (FQHCs) and compare them with usual care (UC). SETTING: Four FQHCs
(3 PCMHs, 1 UC) in Austin, TX, that provide care to the underserved populations.
PRACTICE DESCRIPTION: Pharmacists have worked under a collaborative practice
agreement with internal medicine physicians since 2005. All 4 FQHCs have
pharmacists as an integral part of the health care team. Pharmacists have
prescriptive authority to initiate and adjust diabetes medications. PRACTICE
INNOVATION: The PCMH FQHCs instituted co-visits, where patients see both the
physician and the pharmacist on the same day. PCMH pharmacists are routinely
proactive in collaborating with physicians regarding medication management,
compared with UC in which pharmacists see patients only when referred by a
physician. EVALUATION: Four face-to-face, one-on-one semistructured interviews
were conducted with pharmacists working in 3 PCMH FQHCs and 1 UC FQHC to compare
the implementation of PCMH with emphasis on 1) structure and workflow, 2)
pharmacists' roles, and 3) benefits and challenges. RESULTS: On co-visit days,
the pharmacist may see the patient before or after physician consultation.
Pharmacists in 2 of the PCMH facilities proactively screen to identify diabetes
patients who may benefit from pharmacist services, although the UC clinic
pharmacists see only referred patients. Strengths of the co-visit model include
more collaboration with physicians and more patient convenience. Payment that
recognizes the value of PCMH is one PCMH principle that is not fully implemented.
CONCLUSION: PCMH pharmacists in FQHCs were integrated into the workflow to
address specific patient needs. Specifically, full-time in-house pharmacists,
flexible referral criteria, proactive screening, well defined collaborative
practice agreement, and open scheduling were successful strategies for the
underserved populations in this study. However, reimbursement plans and provider
status for pharmacists should be established to sustain this model of care.
PMID- 28506399
TI - Encouraging pharmacist intervention and standardization of labeling and
dispensing of oral liquid medications.
AB - OBJECTIVES: To initiate a call to action for community pharmacists and key
pharmacy stakeholders in the standardization of oral-liquid dosage forms. DATA
SOURCES: Not applicable. SUMMARY: Unintentional overdose of medication due to
administration error results in thousands of pediatric hospitalizations yearly. A
lack of prescription and dosage device standardization pertaining to oral-liquid
medications continue to be a public health hazard. Multiple professional
organizations have publicly endorsed the standardization of oral liquid dosage
forms. Universal adoption will not be achieved until key-pharmacy stakeholders
encourage their pharmacists to use best practices when verifying and preparing
prescription medication. Specifically, these practices should include immediate
conversion of prescriptions containing non-metric volumes into metric volumes,
providing appropriate sized oral dosing syringes for all oral liquid
prescriptions, writing dosing directions in the safest format, and counseling
patients and caretakers of proper medication administration. CONCLUSION:
Community pharmacists are uniquely positioned to lead the universal adoption of
these best practices to ensure proper oral-liquid dosing administration for all
patients.
PMID- 28506400
TI - Distraction techniques for immunizations in children and adolescents.
PMID- 28506401
TI - Plecanatide, Nusinersen, and Obeticholic acid.
PMID- 28506402
TI - Pharmacists-resource-friendly outcome improvement partners in health care
delivery.
PMID- 28506403
TI - An on-road study of sleepiness in split shifts among city bus drivers.
AB - Bus drivers often work irregular hours or split shifts and their work involves
high levels of stress. These factors can lead to severe sleepiness and dangerous
driving. This study examined how split shift working affects sleepiness and
performance during afternoon driving. An experiment was conducted on a real road
with a specially equipped regular bus driven by professional bus drivers. The
study had a within-subject design and involved 18 professional bus drivers (9
males and 9 females) who drove on two afternoons; one on a day in which they had
driven early in the morning (split shift situation) and one on a day when they
had been off duty until the test (afternoon shift situation). The hypothesis
tested was that split shifts contribute to sleepiness during afternoon, which can
increase the safety risks. The overall results supported this hypothesis. In
total, five of the 18 drivers reached levels of severe sleepiness (Karolinska
Sleepiness Scale >=8) with an average increase in KSS of 1.94 when driving in the
afternoon after working a morning shift compared with being off duty in the
morning. This increase corresponded to differences observed between shift workers
starting and ending a night shift. The Psychomotor Vigilance Task showed
significantly increased response time with split shift working (afternoon:
0.337s; split shift 0.347s), as did the EEG-based Karolinska Drowsiness Score
mean/max. Blink duration also increased, although the difference was not
significant. One driver fell asleep during the drive. In addition, 12 of the 18
bus drivers reported that in their daily work they have to fight to stay awake
while driving at least 2-4 times per month. While there were strong individual
differences, the study clearly showed that shift-working bus drivers struggle to
stay awake and thus countermeasures are needed in order to guarantee safe driving
with split shift schedules.
PMID- 28506404
TI - [Dural sinus thrombosis following epidural analgesia for delivery: a clinical
case].
AB - BACKGROUND AND OBJECTIVES: Neurological complications of spinal anesthesia are
rare conditions. Headache caused by low pressure of the cerebrospinal fluid is
one of the most frequent, which occurs after post-dural puncture. A comprehensive
history and physical exam must be carried out before making the diagnosis of Post
Dural Puncture Headache (PDPH) and additional tests are necessary to exclude the
possibility of developing serious neurological complications such as Dural Sinus
Thrombosis (DST). According to the Case Report a differential diagnosis between
Dural Sinus Thrombosis with PDPH is discussed. CASE REPORT: A 22 year-old lady,
ASA Physical Status Class I was admitted at 39 weeks of gestation for delivery.
For labor pain relief she requested epidural for analgesia, but unfortunately
accidental dural puncture occurred. She developed an occipital headache and neck
pain in the second day postpartum which was relieved by both lying down and
supporting treatment such as rehydration, analgesics and caffeine. On day third
postpartum she was discharged without complaints. On day fifth postpartum the
pain returned and became more intense and less responsive to oral analgesics. She
was admitted to the hospital to do a complete neurological and image
investigation that showed a lesion consistent with the diagnosis of cortical vein
thrombosis and Duhral Sinus Thrombosis (TSD). She was treated with oral
anticoagulants. After two days, a repeated magnetic resonance image (MRI) showed
partial canalization of the central sinus thrombus. The patient was discharged
from hospital five days after her admission without any of the initial symptoms.
CONCLUSION: The report describes a patient who developed severe headache
following continuous epidural analgesia for delivery. Initially it was diagnosed
as PDPH, however with the aid of an MRI the diagnosis of TSD was later
established and treated. TSD is a rare condition and is often underdiagnosed.
Because of its potentially lethal complications, it should always be considered
in acute headache differential diagnosis.
PMID- 28506405
TI - Focus on endocrine surgery.
PMID- 28506406
TI - Adrenal ganglioneuroma: The Padua Endocrine Surgery Unit experience.
AB - BACKGROUND: Adrenal ganglioneuroma (AGN) is a rare tumor that originates from the
gangliar cells of the sympathetic nervous system. It represents less than 5% of
all adrenal masses. AGN occurs as a large mass, with benign behavior and no
relevant symptoms and hormonal secretion, but it is often misdiagnosed because
the preoperative radiological diagnosis is generally challenging. The aim of the
present paper is to report the experience of a tertiary referral academic center
regarding the management of AGN and review the relevant literature. METHODS: The
demographic, diagnostic, surgical, and pathological findings of 666 consecutive
patients who were adrenalectomized at the Padua Endocrine Surgery Unit between
1990 and 2015 were retrospectively reviewed in order to focus on AGN. RESULTS:
The pathology confirmed AGN in 10 patients (1.5% of cases; median age 35 years,
range 19-73). The diagnosis was incidental and never available before surgery.
Eight patients were asymptomatic, two presented lower back and abdominal pain.
The mass was non-secreting in all cases. Preoperative imaging techniques were
inconclusive about the nature of the mass in all cases. The median size of the
tumor was 55 mm (range 30-80). The laparoscopic approach was performed in 60% of
cases. No recurrences occurred after surgery at a median follow-up of 10 years
(range 1.7-18.2). CONCLUSION: The diagnosis of AGN may be challenging and most
often occurs after surgery, since it is frequently confirmed by histological
examination. Radical excision may be achieved by laparoscopic adrenalectomy, with
a subsequent definitive cure and excellent prognosis at long term follow up.
PMID- 28506407
TI - Intraoperative neuromonitoring in thyroid surgery: Is the two-staged
thyroidectomy justified?
AB - BACKGROUND: The aim of this study was to evaluate the diagnostic accuracy of
intraoperative neuromonitoring (IONM) in predicting postoperative nerve function
during thyroid surgery and its consequent ability to assist the surgeon in
intraoperative decision making. MATERIALS AND METHODS: A total of 2365
consecutive patients were submitted to thyroidectomy by the same surgical team.
Group A included 1356 patients (2712 nerves at risk) in whom IONM was utilized,
and Group B included 1009 patients (2018 nerves at risk) in whom IONM was not
utilized. RESULTS: In Group A, loss of signal (LOS) was observed in 37 patients;
there were 29 true positive, 1317 true negative, 8 false positive, and 2 false
negative cases. Accuracy was 99.3%, positive predictive value was 78.4%, negative
predictive value was 99.8%, sensitivity was 93.6%, and specificity was 99.4%. A
total of 29 (2.1%) cases of unilateral paralysis were observed, 23 (1.7%) of
which were transient and 6 (0.4%) of which were permanent. Bilateral palsy was
observed in two (0.1%) cases requiring a tracheostomy. In Group A, 31 (2.3%)
injuries were observed, 25 (1.8%) of which were transient and 6 (0.4%) of which
were permanent. In Group B, 26 (2.6%) unilateral paralysis cases were observed,
20 (2%) of which were transient and 6 (0.6%) of which were permanent; bilateral
palsy was observed in 2 (0.2%) cases. In Group B, 28 (2.8%) injuries were
observed, 21 (2.1%) of which were transient and 7 (0.7%) of which were permanent.
Differences between the two groups were not statistically significant.
CONCLUSIONS: Our results show that IONM has a very high sensitivity and negative
predictive value, but also good specificity and positive predictive value. For
these reasons, in selected patients with LOS, the surgical strategy should be
reconsidered. However, patients need to be informed preoperatively about
potential strategy changes during the planned bilateral surgery. Future larger
and multicenter studies are needed to confirm the benefits of this therapeutic
strategy.
PMID- 28506408
TI - Genetics of medullary thyroid cancer: An overview.
AB - : Medullary thyroid carcinoma (MTC) represents 3-5% of thyroid cancers. 75% is
sporadic and 25% is the dominant component of the hereditary multiple endocrine
neoplasia (MEN) type 2 syndromes. Three different subtypes of MEN2, such as
MEN2A, MEN2B, and Familial MTC (FMTC) have been defined, based on presence or
absence of hyperparathyroidism, pheocromocytoma and characteristic clinical
features. Mutations of the RET proto-oncogene are implicated in the pathogenesis
of MTC, but there are many other mutational patterns involved. In MEN2A, Codon
634 in exon 11 (Cys634Arg), corresponding to a cysteine in the extracellular
cysteine-rich domain, is the most commonly altered codon. Many other mutations
include codons 611, 618, 620. In the genetical testing of RET mutations in MTCs,
Next-Generation Sequencing (NGS) is taking an increasingly important role. One of
the most important benefit is the comprehensive analysis of molecular alterations
in MTC, which allows rapidly to select patients with different risk levels. There
is a difference in miRNA expression pathway between sporadic and hereditary MTCs.
Among sporadic cases, expression of miR-127 was significantly lower in those who
harbor somatic RET mutations than those with wild-type RET. CDKN1B mutations are
associated with many clinical pictures of cancers, such as MEN4. V109G
polymorphism is associated with sporadic MTCs negative for RET mutations, and
might influence the clinical course of the patients affected by MTC. Although
surgery (i.e. total thyroidectomy with neck lymph node dissection) is the
elective treatment for MTCs, about 80% of patients have distant metastases at
diagnosis and in this cases surgery is not enough and an additional treatment is
needed. Interesting results come from two large phase III clinical trials with
two targeted tyrosine kinase inhibitors (TKIs), vandetanib and cabozantinib.
CONCLUSIONS: New genetical testings and therapeutical approaches open new
perspectives in MTC management.
PMID- 28506409
TI - The surgical approach to nodule Thyr 3-4 after the 2.2014 NCCN and 2015 ATA
guidelines.
AB - BACKGROUND: The incidence of palpables thyroid nodules in general population is
5% and the prevalence of non -palpable nodules is higher (35-60%) in the endemic
goiter area. In the last years the new guidelines and new classification related
to thyroid nodule have changed the indication to treat it. MATERIAL AND METHOD:
We analyzed the patients treated from January 2013 to June 2016 for Thyr 3 and
Thyr 4 thyroid nodule sec. Bethesda system. We have divided in I and II period
related to the 2.2014 and 2015 ATA guidelines and we have evaluated the
indication to treat, the type of surgical procedure, the incidence of thyroid
carcinoma and the adverse events. RESULTS: We selected from 909 cases, 252 cases
surgically treated with preoperative diagnosis of Thyr 3(80 cases) and Thyr 4(172
cases); carcinoma was found in 21/80 (26.2%) and in 62/172 (26.05%). The period
was divided from January 2013 to December 2014 and from January 2015 to june 2016
(first and second period). In II period we found carcinoma in 8/40 Thyr3 and in
26/88 Thyr 4. The incidence of lobectomy in II period was higher than I period (p
< 0.0001) sec.guidelines indications. No difference in adverse events. The number
of cancer is lower in patients treated with lobectomy than those who underwent
total thyroidectomy (12,5%vs 21,8% in Thyr 3; 15,3% vs 32% in Thyr 4).
CONCLUSIONS: The indications to treat related to Thyr 3 and Thyr4 are changed in
the two periods. The number of cancer is lower in patients treated with
lobectomy. The new guidelines have changed the surgical approach to thyroid
nodule.
PMID- 28506410
TI - Effectiveness of Intraoperative Parathyroid Monitoring (ioPTH) in predicting a
multiglandular or malignant parathyroid disease.
AB - AIM: The main goal of our study was to confirm the usefulness of intra-operative
parathyroid hormone (PTH) monitoring (ioPTH) when using minimally invasive
techniques for treatment of sporadic Primary hyperparathyroidism (pHTP).
Furthermore, we aimed to evaluate if ioPTH monitoring may help to predict the
etiology of primary hyperparathyroidism, especially in malignant or
multiglandular parathyroid disease. METHODS: A retrospective review of 125
consecutive patients with pHPT who underwent parathyroidectomy between 2001 and
2016 at the Department of General Surgery was performed. For each patient, the
specific preoperative work-up consisted of: high-resolution US of the neck by a
skilled sonographer, sestamibi parathyroid scan, laryngoscopy, and serum
measurement of PTH, serum calcium levels, and serum 25(OH)D levels. RESULTS: The
study included 125 consecutive patients who underwent surgery for pHPT. At the
histological examination, we registered 113 patients with simple adenomatous
pathology (90,4%), 5 atypical adenomas (4%), 3 cases of parathyroid carcinoma
(2,4%),, , and 4 histological exams of different nature (3,2%). Overall, 6 cases
(4,8%) of multiglandular disease were found. We reported 10 cases (8%) of
recurrent/persistent hyperparathyroidism: 1/10 in a patient affected by atypical
adenoma, 9/10 in patients with benign pathology. Regarding these 10 cases, in
three (30%) patients, ioPTH wasn't dosed (only frozen section (FS) exam was
taken), in 5 cases (50%) ioPTH dropped more than 50% compared to basal value
(false negative results), and in 2 (20%) cases, ioPTH did not drop >50% from the
first samples taken, the extemporary exam had confirmed the presence of adenoma
and the probable second hyperfunctioning adenoma was not found. CONCLUSIONS:
IoPTH determinations ensure operative success of surgical resection in almost all
hyperfunctioning tissue; in particular it is very important during minimally
invasive parathyroidectomy, as it allows avoiding bilateral neck exploration. The
use of ioPTH monitoring offer increased sensitivity in detecting multiglandular
disease and can minimize the need and risk associated with recurrent operations,
and may facilitate cost-effective minimally invasive surgery. Moreover,
intraoperative PTH monitoring could be a reliable marker to predict a malignant
disease during parathyroidectomy, showing higher ioPTH baseline value and
superior drop compared to benign disease.
PMID- 28506411
TI - Partial thyroidectomy for papillary thyroid microcarcinoma: Is completion total
thyroidectomy indicated?
AB - AIM: Papillary thyroid microcarcinoma (PTMC) is increasing in incidence. Despite
its excellent clinical outcomes, there is still debate regarding which surgical
approach is more appropriate for PTMC, procedures including hemithyroidectomy
(HT), total thyroidectomy (TT), and completion thyroidectomy (CT) after initial
HT and histopathologic examination confirming a PTMC. Here we report our
experience in the surgical management of PTMC. METHODS: We conducted a
retrospective evaluation of all patients who received a postoperative diagnosis
of PTMC between January 2001 and January 2016. Every patient was divided
according to the type of surgery performed (TT or HT alone). Follow-up consisted
of regular clinical and neck ultrasonographic examination. Clinical and
histopathological parameters (e.g. age, sex, lesion size, histological features,
multifocality, lymph node metastases, BRAF status when available) as well as
clinical outcomes (e.g. complications rates, recurrence, overall survival) were
analyzed. RESULTS: Group A consisted of 86 patients who underwent TT, whereas
Group encompassed 19 patients who underwent HT. Mean follow-up period was 58.5
months. In Group A, one patient (1.2%) experienced recurrence in cervical lymph
nodes with need for reoperation. In Group B, eight patients (42%) underwent
completion thyroidectomy after histopathological examination confirming PTMC,
while one patient (5.3%) developed PTMC in the contralateral lobe with need for
reoperation at 2 years after initial surgery. Multifocality was found in 19
patients in Group A (22%). Of these, 14 presented bilobar involvement, whereas in
3 cases multifocality involved only one lobe. 1 patient in Group B (5.3%)
presented with unilateral multifocal PTMC (p = 0.11). CONCLUSIONS: Low-risk
patients with PTMC may benefit from a more conservative treatment, e.g. HT
followed by close follow-up. However, appropriate selection of patients based on
risk stratification is the key to differentiate therapy options and gain better
results.
PMID- 28506412
TI - Rationality in prophylactic central neck dissection in clinically node-negative
(cN0) papillary thyroid carcinoma: Is there anything more to say? A decade
experience in a single-center.
AB - AIM: Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy.
Despite its extremely favorable prognosis, cervical lymph node metastases are a
common feature of PTC and a known independent risk factor for local recurrence.
However, the role of prophylactic central neck dissection (PCND) remains a matter
of debate in patients with clinically node-negative (cN0) PTC. To better clarify
the current role of PCND in the surgical treatment of PTC, evaluating advantages
and disadvantages of PCND and outcome of cN0 PTC patients who have been treated
with either total thyroidectomy alone or in combination with PCND. A review of
recent literature data is performed. METHODS: Between January 2000 and December
2015, 186 consecutive patients with cN0 PTC were identified to be included in the
present study. 74 of these underwent total thyroidectomy associated with PCND,
while 112 patients underwent total thyroidectomy alone. The epidemiological and
clinical-pathological data of all patients included were collected at diagnosis
and during follow-up. RESULTS: Overall complication rate was significantly higher
in the group of patients undergoing PCND (39.2% vs. 17.8%, p = 0.0006). To be
specific, they presented a considerably increased risk of temporary recurrent
laryngeal nerve injury (p = 0.009) and of permanent hypothyroidism (p = 0.016).
Overall survival and recurrence rates did not differ between those undergoing
PCND and those undergoing total thyroidectomy alone (p = 1.000 and p = 0.715,
respectively). CONCLUSIONS: The results of the present study do not support the
routine use of PCND in the treatment of cN0 PTC patients.
PMID- 28506413
TI - Nasotracheal prolonged safe extubation in acute respiratory failure post
thyroidectomy: An efficacious technique to avoid tracheotomy? A retrospective
analysis of a large case series.
AB - BACKGROUND: Acute respiratory failure is a rare life threatening complication
following thyroid surgery and its incidence is reported as high as 0.9%. Clinical
presentation of severe acute respiratory failure is characterized by dyspnea,
inspiratory airways distress, hypoxia and its standard current management is the
orotracheal intubation and safe extubation. In case of persistent distress,
tracheotomy is mandatory. The Authors, analysing a large acute respiratory
failure clinical series, describe an innovative treatment of this severe
condition: the nasotracheal prolonged safe extubation. METHODS: Patients treated
at our Intensive Care Unit for acute respiratory failure following thyroid
surgery from January 2004 to December 2013, were reviewed. Demographic data
including gender, age, clinical presentation, laryngoscopic findings, management
and outcome during a 24-months follow-up after treatment were collected and
evaluated. Moreover, the strategy for prolonged nasotracheal safe extubation was
carefully described. RESULTS: Nineteen out of the 2853 patients scheduled for
thyroid surgery (0.66%) at our University Hospital, developed post-operative
acute respiratory failure. All of them were treated by nasotracheal prolonged
safe extubation. The success rate in avoiding highly invasive treatment was of
84.2%, since only 3 patients needed definitive tracheotomy (15.7%). CONCLUSIONS:
In our series, the prolonged safe extubation reduced the almost totality of
expected tracheotomies in patients with acute respiratory failure following
thyroid surgery (84.2%), demonstrating its feasibility and efficacy. It was a
well tolerated and minimal invasive procedure that allowed a good respiratory
ability and a fast clinical resolution of the laryngeal functional impairment.
PMID- 28506414
TI - Unintentional recurrent laryngeal nerve injuries following thyroidectomy: Is it
the surgeon who pays the bill?
AB - BACKGROUND: Thyroidectomy is one of the most common intervention in general
surgery and, after the turn of the century, its rate has sharply increased, along
with a worldwide increased incidence of differentiated thyroid cancers.
Therefore, injuries of the recurrent laryngeal nerve have become one of the most
frequent cause of surgical malpractice claims, mostly following surgery for
benign pathology. MAIN BODY: Even if the incidence of definitive paralysis is
generally lower than 3%, during the last 20 years in Italy, the number of claims
for damages has sharply raised. As a consequence, a lot of defensive medicine has
been caused by this issue, and a witch-hunt has been accordingly triggered, so
determining mostly a painful and lasting frustration for the surgeons, who
sometimes are compelled to pay a lot of money for increasing insurance premiums
and lawyers fees. Recurrent laryngeal nerve injury should be considered as a
potentially catastrophic predictable but not preventable event, rather than the
result of a surgical mistake. CONCLUSION: Purposes of the Authors are analyzing
incidence, conditions of risk, and mechanisms of recurrent laryngeal nerve
injuries, underlining notes of surgical technique and defining medical practice
recommendations useful to reduce the risk of malpractice lawsuits and judgments
against surgeons.
PMID- 28506415
TI - Risk of malignancy in thyroid nodules classified as TIR-3A: What therapy?
AB - BACKGROUND: The aim of the present study was to assess the clinical applicability
of the TIR3A category in managing thyroid nodules, to examine the malignancy
rates of TIR 3A and TIR 3B nodules, and to suggest management guidelines for
these nodules. MATERIALS AND METHODS: Thyroid cytologies performed in patients
referred to our Department between January 2014 and August 2016 were classified
according to the guidelines published by the SIAPEC. 102 cases were included in
this retrospective study and were divided into two groups: 19 TIR3A were included
in group A and 83 TIR3B in group B. RESULTS: In group A, malignancy was diagnosed
in 4 (21.1%) cases, papillary thyroid cancer was found in 3 patients and
follicular thyroid cancer in 1; one case was classified as microcarcinoma, in two
cancer was multicentric and bilateral and in one central node metastases were
observed. In Group B malignancy was diagnosed in 48 (57.8%) patients, papillary
thyroid cancer was found in 36 patients and follicular cancer in 12;
microcarcinoma was observed in 25 cases, 12 were unilateral multicentric and 7
bilateral multicentric; in 3 cases central node metastases were present.
CONCLUSION: Thyroid nodules with TIR3A cytology have a lower risk of malignancy
than TIR3B cases, for which the new SIAPEC classification has proved accurate and
effective. Malignancy rates in nodules with TIR3A cytology are higher than
expected, although the real and accurate definition of the risk is extremely
difficult. The recommendation to perform an accurate follow-up and repeat the
fine-needle aspiration still appears the best option. For better management of
patients with TIR3A cytology a careful assessment of risk factors and ultrasound
characteristics is always needed. Further multicenter studies with longer follow
up are needed to better define the efficacy of this classification, the actual
cancer risk, and the best management of these lesions.
PMID- 28506416
TI - Advancement of thyroid surgery video recording: A comparison between two full HD
head mounted video cameras.
AB - BACKGROUND: The aim of this study was to test two different video cameras and
recording systems used in thyroid surgery in our Department. This is meant to be
an attempt to record the real point of view of the magnified vision of surgeon,
so as to make the viewer aware of the difference with the naked eye vision.
MATERIALS AND METHODS: In this retrospective study, we recorded and compared
twenty thyroidectomies performed using loupes magnification and microsurgical
technique: ten were recorded with GoPro(r) 4 Session action cam (commercially
available) and ten with our new prototype of head mounted video camera. RESULTS:
Settings were selected before surgery for both cameras. The recording time is
about from 1 to 2 h for GoPro(r) and from 3 to 5 h for our prototype. The average
time of preparation to fit the camera on the surgeon's head and set the
functionality is about 5 min for GoPro(r) and 7-8 min for the prototype, mostly
due to HDMI wiring cable. Videos recorded with the prototype require no further
editing, which is mandatory for videos recorded with GoPro(r) to highlight the
surgical details. CONCLUSION: the present study showed that our prototype of
video camera, compared with GoPro(r) 4 Session, guarantees best results in terms
of surgical video recording quality, provides to the viewer the exact perspective
of the microsurgeon and shows accurately his magnified view through the loupes in
thyroid surgery. These recordings are surgical aids for teaching and education
and might be a method of self-analysis of surgical technique.
PMID- 28506417
TI - New perspectives in the diagnosis of thyroid follicular lesions.
AB - Thyroid nodules are very common, affecting 19%-67% of the adult population.
However, about 10% of them harbor a malignant lesion. Consequently, the first aim
in their clinical evaluation is to exclude malignancy. Fine-needle aspiration
cytology (FNAC) represents the main diagnostic tool for the evaluation of thyroid
nodules. However, FNAC has a main diagnostic limit, namely cellular atypias of
indeterminate significance, which require surgical excision and histological
examination to differentiate benign from malignant lesions. Histology reports
show that approximately 80% of these patients harbor a benign lesion. Therefore,
in order to reduce unnecessary thyroidectomy, over the last years, the
cytological classification of thyroid nodules has been revised and a number of
new instrumental and molecular approaches have been proposed. In the present
article, we will attempt to summarize the most recent cytological, molecular and
echographic strategies to enhance the diagnostic accuracy of preoperative thyroid
follicular lesions. In particular, we will discuss the new cytological
classifications from the Bethesda System for Reporting Thyroid Cytopathology
(BSRTC), the British Thyroid Association-Royal College of Pathologists (PTA
RCPath) and the new Italian Society for Anatomic Pathology and Cytology (SIAPEC
2014. We will review molecular tests evaluated to ameliorate follicular lesion
diagnosis as well as the clinical utility of the new echographic Thyroid Imaging
Reporting and Data System (TI-RADS) score.
PMID- 28506418
TI - Timing and extension of lymphadenectomy in medullary thyroid carcinoma: A case
series from a single institution.
AB - BACKGROUND: Medullary thyroid carcinoma is an aggressive tumor and presents with
significant morbidity and mortality and a high rate of lymph node metastases. The
combination of total thyroidectomy and cervical lymphadenectomy is the essential
treatment for those patients presenting with cervical lymph node metastases.
MATERIALS AND METHODS: A retrospective analysis of 117 patients operated for
medullary thyroid carcinoma over a period of 15 years at a single institution.
Surgical complications and calcitonin levels were noted. RESULTS: Nodal
metastases were detected in the central compartment in 72.6% patients. Positive
lymph nodes were detected in the lateral compartment of 34 patients who had
undergone ipsilateral dissection and in all 10 patients of those with bilateral
surgery. We found 3 cases of unilateral transient recurrent laryngeal nerve
palsy, 15 cases of temporary hypoparathyroidism, a permanent accessory nerve
lesion and a case of chylous fistula. Normalization of post-operative calcitonin
was found in 82.6% and of patients who underwent total thyroidectomy and central
neck dissection alone compared to 35.4% in those with ipsilateral and bilateral
neck dissection. CONCLUSIONS: Total thyroidectomy and cervical lymphadenectomy
planned on the ultrasound preoperative study and on the calcitonin level
represent the standard of treatment for medullary thyroid carcinoma.
PMID- 28506419
TI - Radioguided thyroidectomy for follicular tumors: Multicentric experience.
AB - BACKGROUND: The diagnosis of thyroid nodular diseases requires an integrated
approach that has been widely established over the past years. This strategy
includes: ultrasonography (US) with; implemented Color-Power-Doppler,
conventional scintigraphy also with positive indicators, specific pathological
studies targeted by immunohistochemically-assays, and the fine needle; aspiration
biopsy (FNAB), which, usually, in case of "Follicular Lesions" (10-20%) findings
is; unable to distinguish carcinoma from follicular adenoma, then indicating the
necessity of surgery to; obtain a correct diagnosis. The aim of this study was to
evaluate the role of the scintigraphy with; positive indicators, both
preoperatively in diagnostic approach of the thyroid nodules and;
intraoperatively as a guide to the extension of the surgical excision. METHODS:
On 4482 Thyroidectomy performed, we selected 360 cases of follicular neoplasms
(192; females and 168 males). In the preoperative phase, these patients underwent
99 m Tc-sestaMIBI; scintigraphy with both early (10 min) and late (2 h) image
acquisition, which were later; compared to the ones obtained by image subtraction
of means 99 m Tc-pertechnetate. Following the; sestamibi administration before
intervention, we selected the most up-taking nodularity with the; assistance of a
specific surgical probe (Neoprobe), quantifying uptake with relation to the
surgical pathology, for an amount of 324 total thyroidectomies and 36 hemi
thyroidectomies. RESULTS: In all cases of multinodular goiter the benign nodules
showed an intraoperative low sestamibi uptake whereas follicular carcinomas
showed both a high preoperative uptake and, as a; percentage, the highest values
of intraoperative uptake; on the other hand, follicular adenomas had; both pre
and intraoperative mean values of uptake. On the contrary, papillary carcinomas
only; showed a mild uptake. CONCLUSIONS: Preoperative sestamibi scintigraphy
confirmed its importance in improving the information obtained through different
diagnostic investigations. Also intraoperatively, it pointed; out high-risk
nodules more accurately. Therefore, radio (Sestamibi) guided surgery could have
an; interesting rule in the thyroid follicular lesion treatment.
PMID- 28506420
TI - Update on the role of ultrasound guided radiofrequency ablation for thyroid
nodule treatment.
AB - Thyroid nodules can be frequently detected in general population, most of them
are benign, however malignant cases are rising in the past decades. Ultrasound
(US) is the most common imaging modality to assess thyroid nodular lesions, plan
patient work-up and guide minimally invasive treatment. The present review paper
has been researched to evaluate the current status of radiofrequency ablation
(RFA) treatment in order to evaluate indications, techniques, complications,
limitations and outcome assessment in benign solid, partially cystic nodules and
recurrent malignant nodules. RFA comparison with other ablation techniques has
been provided as well. US guided Radiofrequency ablation has been proved to be
effective and safe in cases of benign thyroid nodules and a promising treatment
method alternative to surgery for patients with recurrent papillary thyroid
cancer. It's major role lies in significant reduction of thyroid nodule mean
volume and improvement of the patient symptoms. However, future multicenter
studies are warranted to better clarify the multi-parametric patient selection
criteria and evaluate RFA technique efficacy, advantages and limitations in the
variety of thyroid nodular disease.
PMID- 28506421
TI - Swallowing disorders after thyroidectomy: What we know and where we are. A
systematic review.
AB - INTRODUCTION: Dysphagia and hoarseness are possible complications that can be
observed in patients undergoing thyroidectomy or other neck surgery procedures.
These complaints are usually related to superior and inferior laryngeal nerves
dysfunction, but these can appear even after uncomplicated surgical procedure.
METHODS: We reviewed the current literature available on MEDLINE database,
concerning the swallowing disorders appearing after the thyroidectomy. The
articles included in the review reported pathophysiology and diagnostic concerns.
RESULTS: Twenty articles were selected for inclusion in the review. Depends on
the possible causes of the difficulty swallowing (related to nerve damage or
appearing after uncomplicated thyroidectomy), different types of diagnostic
procedures could be used to study patient discomfort, as well as intraoperative
nerve monitoring, fiber optic laryngoscopy, endoscopy, pH monitoring, esophageal
manometry and videofluorography. Among all these procedures, videofluorography is
considered the gold standard to evaluate the entire swallowing process, since
that allows a real-time study of all the three phases of swallowing: oral phase,
pharyngeal phase and esophageal phase. CONCLUSION: The diagnostic procedures
described can help to identify the mechanisms involved in swallowing disorders,
with the aim to choose the best therapeutic option. More studies are needed for
understanding the causes of the dysphagia appearing after thyroidectomy.
PMID- 28506422
TI - Epinephrine use and training in schools for food-induced anaphylaxis among non
nursing staff.
PMID- 28506423
TI - A case of recurrent facial angioedema associated with elevated tree pollen
counts.
PMID- 28506424
TI - Increased risk of systemic reactions extends beyond completion of rush
immunotherapy.
PMID- 28506425
TI - Fluoroquinolone resistance in Streptococcus pneumoniae isolates in Germany from
2004-2005 to 2014-2015.
AB - Streptococcus pneumoniae is a major cause of bacterial pneumonia, sepsis and
meningitis worldwide. Prevalence of levofloxacin-resistant S. pneumoniae isolates
in Germany and associated mutations in the quinolone resistance determining
regions (QRDRs), as well as serotype distribution and multi locus sequence types
(MLST) are shown. 21,764 invasive S. pneumoniae isolates from Germany, isolated
in the epidemiological seasons from 2004/05 to 2014/15 were analyzed at the
German National Reference Centre for Streptococci (GNRCS) for their levofloxacin
resistance by micro broth dilution method. All resistant (minimal inhibitory
concentration (MIC) >=8MUg/ml) and intermediate (MIC >2MUg/ml and <8MUg/ml)
isolates were selected for the present study. Additionally, 29 susceptible
isolates were randomly selected. A total of ninety isolates were tested for their
levofloxacin-MIC by Etest, their serotype and sequence type, as well as for point
mutations at the QRDRs in the genes parC, parE, gyrA and gyrB. Twenty-five
isolates exhibited levofloxacin MICs <2MUg/ml (Etest) and no mutations in the
QRDRs. Four isolates with MICs=2MUg/ml had one mutation in parC; isolates with
MICs >2MUg/ml all had one or more mutations in the QRDRs. Four of nine
intermediate isolates had a mutation in either parC or gyrA, and four isolates
had mutations in both parC and gyrB. One isolate had mutations in both parC and
gyrA. All isolates with MICs >=8MUg/ml (52) had mutations in both topoisomerase
IV and gyrase. Serotypes associated with levofloxacin resistance shifted from a
majority of PCV13 serotypes before the introduction of the PCV13 vaccine towards
non-PCV serotypes. Resistant isolates were almost exclusively found among adults
(98.1%).
PMID- 28506426
TI - Heterogeneity of FHF1 related phenotype: Novel case with early onset severe
attacks of apnea, partial mitochondrial respiratory chain complex II deficiency,
neonatal onset seizures without neurodegeneration.
AB - INTRODUCTION/OBJECTIVES: We report the case of a child prospectively followed in
our institution for a severe, neonatal onset epilepsy presenting with severe
attacks of apnea that were not initially recognized as seizure since they were
not associated with any abnormal movement and since interictal EEG was normal.
Recording of attacks using prolonged video-EEG recording allowed to confirm the
diagnosis of epileptic seizures. RESULTS: Using whole exome sequencing we found a
de novo heterozygous, missense mutation of FHF1 (p.Arg52His, NM_004113), a
mutation that has been very recently described in 7 patients with an early onset
epileptic encephalopathy. The initial workup showed a partial deficit of the
complex II of the respiratory chain in muscle and liver. The prospective follow
up demonstrated that 2 drugs seemed to be more effective than the others: sodium
blocker carbamazepine, and serotonin reuptake blocker fluoxetine. GABAergic drugs
seemed to be ineffective. No drug aggravated the epilepsy. DISCUSSION: This case
report contributes to the description of an emerging phenotype for this
condition.
PMID- 28506427
TI - Italy introduces pre and post operation monitoring phases for offshore seismic
exploration activities.
AB - Concern is growing that marine fauna can be affected by noise such as naval
sonar, pile driving or geophysical surveys, among others. Literature reports a
variety of animal reactions to human noise (from apparently null or negligible to
strong). However, conclusive results on its effects on marine mammals at
individual and population level are still lacking. In 2015, the Italian
Environmental Impact Assessment Commission mandated seismic operators apply a
standard scientific protocol comparing marine mammal presence before, during, and
after offshore seismic survey. For 60days before and after the survey, marine
mammals are monitored using visual and acoustic methods. One or more acoustic
autonomous recorders, depending on area size, must also be deployed throughout
the three phases for continuous monitoring. Consistent data gathered from many
surveys will enable robust statistical analysis of results. Diffusion of this
monitoring method internationally would improve the study of far-reaching,
intense, low frequency noise.
PMID- 28506428
TI - Polycyclic aromatic hydrocarbons and heavy metals in the Cispata Bay, Colombia: A
marine tropical ecosystem.
AB - The concentrations of polycyclic aromatic hydrocarbons and heavy metals were
evaluated in shallow sediments, water, fish and seabird samples from the Cispata
Bay, Colombia. The heavy metals concentrations in the sediment was in the
following order: Cu>Pb>Hg>Cd. The heavy metal concentration was different
(p<0.05) in juvenile and adult birds. High concentrations of mercury were
registered in the seabird (10.19+/-4.99mgkg-1) and fish (0.67MUgg-1) samples. The
total concentration of polycyclic aromatic hydrocarbons ranged from 7.0-41ngg-1
in sediment, 0.03-0.34ngmL-1 in water samples, 53.24ngg-1 in fish, and 66ngg-1 in
seabirds. The high concentrations of heavy metals in seabirds may be explained by
their feeding habits. The presence of polycyclic aromatic hydrocarbons in the
Cispata Bay may be due to hydrocarbon spills during oil transport at the nearby
oil port.
PMID- 28506429
TI - Deteriorating respiratory health in Nepal: a call for action.
PMID- 28506430
TI - George E. Palade memorial lecture: My life in pancreatic research-unexpected
results may open the door.
AB - The Palade Prize is the most distinguished award of the IAP for achievement in
pancreatic research. It is named after George E. Palade, who in 1974 was awarded
the Nobel Prize for his work on protein trafficking in pancreatic acinar cells.
It is a great honor to be awarded the 2016 Palade Prize. While I was in graduate
school, I was conducting research on hypothalamo-pituitary-thyroid axis; after
finishing graduate school, I began research on amylase isoenzymes. This was the
first step of my pancreatic research. Once I discovered that there are close
relationships among blood glucose levels, amylase activity, and exocrine
pancreatic function, I continued on to the next challenge. I performed research
on the relationship between exocrine and endocrine aspects of the pancreas,
pancreatic exocrine functions in diabetes mellitus, the role of cholecystokinin
(CCK) and its synthetic analogue on exocrine and endocrine pancreas function, the
role of CCK on the pathogenesis of pancreatitis, the cellular mechanisms of
reversible and irreversible pancreatitis, and pancreatic stellate cell
activation. In addition, I established guidelines for the diagnosis and
management of acute, chronic and autoimmune pancreatitis as a chief investigator
of the Research Committee of Intractable Pancreatic Diseases supported by the
Ministry of Health, Labour and Welfare in Japan.
PMID- 28506431
TI - Usefulness of three-dimensional magnetic resonance cholangiopancreatography with
partial maximum intensity projection for diagnosing autoimmune pancreatitis.
AB - PURPOSE: To compare three-dimensional magnetic resonance cholangiopancreatography
(MRCP) with/without partial maximum intensity projection (MIP) and endoscopic
retrograde cholangiopancreatography (ERCP) in patients with autoimmune
pancreatitis (AIP). MATERIALS AND METHODS: Three-dimensional MRCP and ERCP images
were retrospectively analyzed in 24 patients with AIP. We evaluated the narrowing
length of the main pancreatic duct (NR-MPD), multiple skipped MPD narrowing (SK
MPD), and side branches arising from the narrowed portion of the MPD (SB-MPD)
using four MRCP datasets: 5 original images (MIP5), 10 original images (MIP10),
all original images (full-MIP), and a combination of these three datasets (a
MIP). The images were scored using a 3- or 5-point scale. The scores of the four
MRCP datasets were statistically analyzed, and the positive rate of each finding
was compared between MRCP and ERCP. RESULTS: The median scores for SB-MPD on MIP5
and a-MIP were significantly higher than those on MIP10 and full-MIP. In other
words, partial MIP is superior to full-MIP for visualization of detailed
structures. The positive rate for SB-MPD on full-MIP was significantly lower than
that on ERCP, whereas the positive rate on MIP5, MIP10, and a-MIP was not
significantly different from that on ERCP. Moreover, the positive rate for NR-MPD
and SK-MPD on the MRCP images was significantly higher than that on the ERCP
images. CONCLUSION: Partial MIP is useful for evaluating the MPD and is
comparable with ERCP for diagnosing AIP.
PMID- 28506432
TI - The ICUC(r) app: Can it pave the way for quality control and transparency in
medicine?
PMID- 28506433
TI - Awareness in the crowd: Beta power and alpha phase of prestimulus oscillations
predict object discrimination in visual crowding.
AB - Visual crowding is among the factors that most hamper conscious object
perception. However, we currently ignore the neural states that predispose to an
accurate perception within different crowding regimes. Here, we performed single
trial analyses of the electroencephalographical (EEG) oscillations, evaluating
the prestimulus power and phase differences between correct and incorrect
discrimination during a letter-crowding task, where irrelevant letters were
placed nearby (strong crowding) or far (mid crowding) relative to the target.
Results show that prestimulus alpha (8-12Hz) power was related to target
discrimination in the mid, but not in the strong, crowding condition.
Importantly, accurate discrimination in the strong crowding condition was
predicted by the phase of alpha and by the power of beta (13-20Hz) oscillations.
These evidence suggest that both periodic visual sampling mechanisms, reflected
in the alpha phase, and network predisposition to extract local information,
reflected in the beta power, predispose to object discrimination in a crowded
scene.
PMID- 28506434
TI - ERP signatures of conscious and unconscious word and letter perception in an
inattentional blindness paradigm.
AB - A three-phase inattentional blindness paradigm was combined with ERPs. While
participants performed a distracter task, line segments in the background formed
words or consonant-strings. Nearly half of the participants failed to notice
these word-forms and were deemed inattentionally blind. All participants noticed
the word-forms in phase 2 of the experiment while they performed the same
distracter task. In the final phase, participants performed a task on the word
forms. In all phases, including during inattentional blindness, word-forms
elicited distinct ERPs during early latencies (~200-280ms) suggesting unconscious
orthographic processing. A subsequent ERP (~320-380ms) similar to the visual
awareness negativity appeared only when subjects were aware of the word-forms,
regardless of the task. Finally, word-forms elicited a P3b (~400-550ms) only when
these stimuli were task-relevant. These results are consistent with previous
inattentional blindness studies and help distinguish brain activity associated
with pre- and post-perceptual processing from correlates of conscious perception.
PMID- 28506435
TI - A Practical Approach and Model of Care for HCV Treatment With Direct Acting
Antivirals in an Urban Setting.
PMID- 28506436
TI - Silence = Defunding, New Infections, Social Injustice, and Death.
PMID- 28506437
TI - Association Between Interleukin-6 and Striatal Prediction-Error Signals Following
Acute Stress in Healthy Female Participants.
AB - BACKGROUND: Stress is widely known to alter behavioral responses to rewards and
punishments. It is believed that stress may precipitate these changes through
modulation of corticostriatal circuitry involved in reinforcement learning and
motivation, although the intervening mechanisms remain unclear. One candidate is
inflammation, which can rapidly increase following stress and can disrupt
dopamine-dependent reward pathways. METHODS: Here, in a sample of 88 healthy
female participants, we first assessed the effect of an acute laboratory stress
paradigm on levels of plasma interleukin-6 (IL-6), a cytokine known to be both
responsive to stress and elevated in depression. In a second laboratory session,
we examined the effects of a second laboratory stress paradigm on reward
prediction error (RPE) signaling in the ventral striatum. RESULTS: We show that
individual differences in stress-induced increases in IL-6 (session 1) were
associated with decreased ventral striatal RPE signaling during reinforcement
learning (session 2), though there was no main effect of stress on RPE.
Furthermore, changes in IL-6 following stress predicted intraindividual
variability in perceived stress during a 4-month follow-up period. CONCLUSIONS:
Taken together, these data identify a novel link between IL-6 and striatal RPEs
during reinforcement learning in the context of acute psychological stress, as
well as future appraisal of stressful life events.
PMID- 28506439
TI - Clinical Review: Loperamide Toxicity.
AB - Loperamide is a nonprescription opioid widely used for the treatment of diarrhea.
Although it is relatively safe at therapeutic doses, increasing reports describe
its misuse and abuse at very high doses either for euphoric effects or to
attenuate symptoms of opioid withdrawal. Life-threatening loperamide toxicity can
result from the relatively new clinical syndrome of loperamide-induced cardiac
toxicity. These patients are often young and may present in cardiac arrest or
with unheralded, recurrent syncope in conjunction with ECG abnormalities,
including marked QT-interval prolongation, QRS-interval widening, and ventricular
dysrhythmias. Features of conventional opioid toxicity may also be present. The
mainstays of treatment include advanced cardiac life support and supportive care,
although selected patients may be candidates for overdrive pacing, intravenous
lipid emulsion, or extracorporeal membrane oxygenation. In patients who survive
loperamide toxicity, consideration should be given to the treatment of an
underlying opioid use disorder, if present.
PMID- 28506438
TI - Prion-like Spreading in Tauopathies.
AB - Tau is a microtubule-associated protein that functions in regulating cytoskeleton
dynamics, especially in neurons. Misfolded and aggregated forms of tau produce
pathological structures in a number of neurodegenerative diseases, including
Alzheimer's disease (AD) and tauopathy dementias. These disorders can present
with a sporadic etiology, such as in AD, or a familial etiology, such as in some
cases of frontotemporal dementia with parkinsonism. Notably, the pathological
features of tau pathology in these diseases can be very distinct. For example,
the tau pathology in corticobasal degeneration is distinct from that of an AD
patient. A wealth of evidence has emerged within the last decade to suggest that
the misfolded tau in tauopathies possesses prion-like features and that such
features may explain the diverse characteristics of tauopathies. The prion-like
concept for tauopathies arose initially from the observation that the progressive
accumulation of tau pathology as the symptoms of AD progress seemed to follow
anatomically linked pathways. Subsequent studies in cell and animal models
revealed that misfolded tau can propagate from cell to cell and from region to
region in the brain through direct neuroanatomical connections. Studies in these
cell and mouse models have demonstrated that experimentally propagated forms of
misfolded tau can exist as conformationally distinct "strains" with unique
biochemical, morphological, and neuropathological characteristics. This review
discusses the clinical, pathological, and genetic diversity of tauopathies and
the discoveries underlying the emerging view that the unique features of
clinically distinct tauopathies may be a reflection of the strain of misfolded
tau that propagates in each disease.
PMID- 28506440
TI - The Wistar Audiogenic Rat (WAR) strain and its contributions to epileptology and
related comorbidities: History and perspectives.
AB - In the context of modeling epilepsy and neuropsychiatric comorbidities, we review
the Wistar Audiogenic Rat (WAR), first introduced to the neuroscience
international community more than 25years ago. The WAR strain is a genetically
selected reflex model susceptible to audiogenic seizures (AS), acutely mimicking
brainstem-dependent tonic-clonic seizures and chronically (by audiogenic
kindling), temporal lobe epilepsy (TLE). Seminal neuroethological,
electrophysiological, cellular, and molecular protocols support the WAR strain as
a suitable and reliable animal model to study the complexity and emergent
functions typical of epileptogenic networks. Furthermore, since epilepsy
comorbidities have emerged as a hot topic in epilepsy research, we discuss the
use of WARs in fields such as neuropsychiatry, memory and learning,
neuroplasticity, neuroendocrinology, and cardio-respiratory autonomic regulation.
Last, but not least, we propose that this strain be used in "omics" studies, as
well as with the most advanced molecular and computational modeling techniques.
Collectively, pioneering and recent findings reinforce the complexity associated
with WAR alterations, consequent to the combination of their genetically
dependent background and seizure profile. To add to previous studies, we are
currently developing more powerful behavioral, EEG, and molecular methods,
combined with computational neuroscience/network modeling tools, to further
increase the WAR strain's contributions to contemporary neuroscience in addition
to increasing knowledge in a wide array of neuropsychiatric and other
comorbidities, given shared neural networks. During the many years that the WAR
strain has been studied, a constantly expanding network of multidisciplinary
collaborators has generated a growing research and knowledge network. Our current
and major wish is to make the WARs available internationally to share our
knowledge and to facilitate the planning and execution of multi-institutional
projects, eagerly needed to contribute to paradigm shifts in epileptology. This
article is part of a Special Issue entitled "Genetic and Reflex Epilepsies,
Audiogenic Seizures and Strains: From Experimental Models to the Clinic".
PMID- 28506441
TI - Association of traumatic brain injury and Alzheimer disease onset: A systematic
review.
AB - BACKGROUND: Inconsistencies regarding the risk of developing Alzheimer disease
after traumatic brain injury (TBI) remain in the literature. Indeed, why AD
develops in certain TBI patients while others are unaffected is still unclear.
OBJECTIVE: The aim of this study was to performed a systematic review to
investigate whether certain variables related to TBI, such as TBI severity, loss
of consciousness (LOC) and post-traumatic amnesia (PTA), are predictors of risk
of AD in adults. METHODS: From 841 citations retrieved from MEDLINE via PubMed,
EMBASE, PSYINFO and Cochrane Library databases, 18 studies were eligible for the
review. RESULTS: The review revealed that about 55.5% of TBI patients may show
deteriorated condition, from acute post-TBI cognitive deficits to then meeting
diagnostic criteria for AD, but whether TBI is a risk factor for AD remains
elusive. CONCLUSIONS: Failure to establish such a link may be related to
methodological problems in the studies. To shed light on this dilemma, future
studies should use a prospective design, define the types and severities of TBI
and use standardized AD and TBI diagnostic criteria. Ultimately, an AD prediction
model, based on several variables, would be useful for clinicians detecting TBI
patients at risk of AD.
PMID- 28506442
TI - Boosting syntax training with temporally regular musical primes in children with
cochlear implants.
AB - OBJECTIVES: Previous research has suggested the use of rhythmic structures
(implemented in musical material) to improve linguistic structure processing
(i.e., syntax processing), in particular for populations showing deficits in
syntax and temporal processing (e.g., children with developmental language
disorders). The present study proposes a long-term training program to improve
syntax processing in children with cochlear implants, a population showing syntax
processing deficits in perception and production. METHODS: The training program
consisted of morphosyntactic training exercises (based on speech processing) that
were primed by musical regular primes (8 sessions) or neutral baseline primes
(environmental sounds) (8 sessions). A crossover design was used to train 10 deaf
children with cochlear implants. Performance in grammatical processing, non-word
repetition, attention and memory was assessed before and after training. RESULTS:
Training increased performance for syntax comprehension after both prime types
but for grammaticality judgements and non-word repetition only when musical
primes were used during training. For the far-transfer tests, some effects were
also observed for attention tasks, especially if fast and precise sequential
analysis (sequencing) was required, but not for memory tasks. CONCLUSIONS: The
findings extend the previously observed beneficial short-term effects of regular
musical primes in the laboratory to long-term training effects. Results suggest
that the musical primes improved the processing of the syntactic training
material, thus enhancing the training effects on grammatical processing as well
as phonological processing and sequencing of speech signals. The findings can be
interpreted within the dynamic attending theory (postulating the modulation of
attention over time) and associated oscillatory brain activity. Furthermore, the
findings encourage the use of rhythmic structures (even in non-verbal materials)
in language training programs and outline perspectives for rehabilitation.
PMID- 28506444
TI - Monocyte lineage-derived IL-6 does not affect chimeric antigen receptor T-cell
function.
AB - BACKGROUND AIMS: Chimeric antigen receptor (CAR) T-cell therapy targeting CD19
has demonstrated remarkable success in targeting B-cell malignancies but is often
complicated by serious systemic toxicity in the form of cytokine release syndrome
(CRS). CRS symptoms are primarily mediated by interleukin 6 (IL-6), and clinical
management has focused on inhibition of IL-6 signaling. The cellular source and
function of IL-6 in CRS remain unknown. METHODS: Using co-culture assays and data
from patients on our clinical CAR T-cell trials, we investigated the cellular
source of IL-6, as well as other CRS-associated cytokines, during CAR T-cell
activation. We also explored the effect that IL-6 has on T-cell function.
RESULTS: We demonstrated that IL-6 is secreted by monocyte-lineage cells in
response to CAR T-cell activation in a contact-independent mechanism upon T-cell
engagement of target leukemia. We observed that the presence of antigen
presenting cell-derived IL-6 has no impact on CAR T-cell transcriptional profiles
or cytotoxicity. Finally, we confirm that CAR T cells do not secrete IL-6 in vivo
during clinical CRS. DISCUSSION: These findings suggest that IL-6 blockade will
not affect CD19 CAR T-cell-driven anti-leukemic cytotoxicity, permitting enhanced
control of CRS while maintaining CAR T-cell efficacy.
PMID- 28506445
TI - Comparison of Features of Fatal Versus Nonfatal Cardiac Arrest in Patients With
Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy.
AB - Once arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is
diagnosed, the incidence of sudden cardiac death (SCD) is rare and prognosis is
favorable, highlighting the value of early disease recognition. To inform
strategies to diagnose ARVD/C before SCD, we sought to characterize clinical,
genetic, and family history features of ARVD/C cases first recognized after SCD
or resuscitated SCD (sudden cardiac arrest [SCA]). We identified 66 ARVD/C cases
submitted to the Johns Hopkins ARVD/C Registry in whom disease was first
recognized after SCD (n = 45) or SCA (n = 21) and compared their clinical,
genetic, and demographic features with 352 patients (227 probands) diagnosed with
ARVD/C by 2010 Task Force Criteria before any arrest. SCD/SCA cases were 65% men
and experienced their arrest at 29.3 +/- 13.8 years. Exertion precipitated 72% of
arrests. Family history was recognized before arrest in 11 cases (17%), and 24
cases (41%) had reported cardiac symptoms before arrest. The SCD/SCA cohort was
disproportionately men (65% SCD/SCA vs 50% living, p = 0.03) and younger at both
first reported symptom (27.7 +/- 13.5 years SCD/SCA vs 33.0 +/- 13.6 years
living, p = 0.01) and first sustained ventricular arrhythmia (VA) (29.3 +/- 13.8
years SCD/SCA vs 35.6 +/- 12.9 years living, p <0.001). In addition, survival
from first symptom to VA was significantly shorter in SCD/SCA cases (p <0.001).
These results suggest that the natural history of ARVD/C may be accelerated in
SCD/SCA cases. In conclusion, although symptoms or family history provide a
window of opportunity for diagnosis before death, time to intervene after symptom
onset is limited.
PMID- 28506443
TI - Endoplasmic reticulum-resident selenoproteins as regulators of calcium signaling
and homeostasis.
AB - The human selenoprotein family contains 25 members that share the common feature
of containing the amino acid, selenocysteine (Sec). Seven selenoproteins are
localized to the endoplasmic reticulum (ER) and exhibit different structural
features contributing to a range of cellular functions. Some of these functions
are either directly or indirectly related to calcium (Ca2+) flux or homeostasis.
The presence of the unique Sec residue within these proteins allows some to exert
oxidoreductase activity, while the function of the Sec in other ER selenoproteins
remains unclear. Some functional insight has been achieved by identifying domains
within the ER selenoproteins or through the identification of binding partners.
For example, selenoproteins K and N (SELENOK AND SELENON) have been characterized
through interactions detected with the inositol 1,4,5-triphosphate receptors
(IP3Rs) and the SERCA2b pump, respectively. Others have been linked to chaperone
functions related to ER stress or Ca2+ homeostasis. This review summarizes the
details gathered to date regarding the ER-resident selenoproteins and their
effect on Ca2+ regulated pathways and outcomes in cells.
PMID- 28506446
TI - Serum 24,25-dihydroxyvitamin D3 response to native vitamin D2 and D3
Supplementation in patients with chronic kidney disease on hemodialysis.
AB - BACKGROUND & AIMS: While vitamin D deficiency is common in patients with end
stage renal disease on dialysis and treatment with Vitamin D2 and Vitamin D3 is
becoming increasingly common in these patients, little is known about
24,25(OH)2D3 metabolite production. Some authors report that the CYP24A1 enzyme
is upregulated in CKD, but reports of low serum levels of 24,25(OH)2D3 in these
patients bring this into question. Lack of substrate or increased clearance of
the metabolite have been proposed as possible causes. We report serum
24,25(OH)2D3 levels from three controlled trials of Vitamin D2 and Vitamin D3
supplementation which reached adequate levels of 25(OH)D in patients with end
stage renal disease on dialysis. METHODS: 680 samples from three controlled
trials of Vitamin D2 or Vitamin D3 supplementation in CKD Stage 5D were available
for analysis. The trials used single doses of 50,000 IU Vitamin D3, or 50,000 IU
Vitamin D2, or weekly doses of 10,000 IU or 20,000 IU Vitamin D3. Blood samples
were drawn at baseline and frequently over the ensuing 3-4 months. Serum 25(OH)D
and 24,25(OH)2D3 levels were measured using a novel, very sensitive LC-MS/MS
based method involving derivatization with DMEQ-TAD. Linear mixed effect
regression models were used to compare the 3 studies and the interventions within
studies over time. RESULTS: The subjects given Vitamin D3 had significant
increases in 25(OH)D levels. Serum 24,25(OH)2D3 levels were low at baseline in
the renal patients and rose slightly with native vitamin D supplementation, but
these levels were lower than reports of 24,25(OH)2D3 in healthy populations.
CONCLUSIONS: We conclude that the enzymatic activity of CYP24A1 is abnormal in
end stage renal patients on dialysis. These trials were registered on
clinicaltrials.govNCT00511225 on 8/1/2007; NCT01325610 on 1/17/2011; and
NCT01675557 on 8/28/2012.
PMID- 28506448
TI - The differential effects of changes in individual macronutrient intake on changes
in lipid concentrations during childhood: From the Ewha Birth & Growth Cohort.
AB - BACKGROUND & AIMS: High carbohydrate or fat intake is responsible for abnormal
lipid concentrations in adults, but few studies of children have been reported.
Using data from a Korean children's cohort study, we assessed the association
between macronutrient intake and lipid profile with a longitudinal association
during a 4-year follow-up. METHODS: Using 2 days of 24-h dietary data obtained at
3 (n = 323) and 7 (n = 292) years old from the Ewha Birth & Growth Cohort, we
calculated changes (n = 103) in macronutrient intake in terms of energy-adjusted
intake and percent total energy for nutrients. Changes in lipid profiles (TC:
total cholesterol, TG: triglyceride, HDL-c: high-density lipoprotein cholesterol,
LDL-c: low-density lipoprotein cholesterol) are the primary outcomes in this
study. The effects of individual changes in macronutrient intake on changes in
lipid profiles over time were assessed using multiple regression analyses.
RESULTS: The percentages of total energy from carbohydrates and fat were 59.1%
and 27.4% at baseline, respectively. Those in the highest tertile of carbohydrate
intake showed the highest mean TG and lowest mean TC and HDL-c levels, regardless
of observation time. By contrast, those with the highest fat intake indicated the
lowest mean TG and highest mean TC and HDL-c at 7 years old. In addition,
increased intake of carbohydrates had an unfavorable effect on TG, while
increased intake of fat, especially animal-based fat, increased LDL-c levels over
time. CONCLUSIONS: Our study showed that a relatively high intake of carbohydrate
or fat among children had an unfavorable effect on lipid concentrations based on
a longitudinal approach.
PMID- 28506447
TI - Effects of continuous use of probiotics before liver transplantation: A
randomized, double-blind, placebo-controlled trial.
AB - BACKGROUND & AIMS: Although there is increasing evidence for the benefits of
probiotics in patients with liver diseases, data on the benefits of pre-LT
administration of probiotics are lacking. The aim of this study was to evaluate
the effects of continuous administration of probiotics before liver
transplantation (LT) on pre- and post-transplant patient outcomes. METHODS: In
this randomized, double-blind, and placebo-controlled trial adult cirrhotic
patients listed for LT received a 4-strain probiotic preparation or placebo daily
from enrollment until LT. The primary outcome measures were postoperative
mortality and infection rates. The secondary outcome measures were 5-day post
transplant aspartate and alanine aminotransferase activities, bilirubin
concentration, and international normalized ratio; waiting-list mortality; pre
transplant Model for End-stage Liver Disease score and Child-Turcotte-Pugh class
changes; and pre-transplant infections. RESULTS: A total of 55 patients were
randomized. The 90-day postoperative mortality rates were 0% and 4.3% in the
probiotic and placebo groups, respectively (p > 0.99). Patients receiving
probiotics had significantly reduced 30-day (4.8% versus 34.8%, p = 0.02) and 90
day (4.8% versus 47.8%, p = 0.002) infection rates, lower post-LT bilirubin
concentration (p = 0.02), and more rapid decrease of aspartate (p = 0.03) and
alanine (p = 0.03) aminotransferase activities. Probiotics did not have
significant effects on other secondary outcome measures. CONCLUSIONS: Although
continuous administration of probiotics before LT does not appear to affect
postoperative mortality, it effectively prevents postoperative infections and
improves early biochemical parameters of allograft function. CLINICALTRIALS. GOV
IDENTIFIER: NCT01735591.
PMID- 28506450
TI - Utility and versatility of the supraclavicular artery island flap in head and
neck reconstruction.
AB - INTRODUCTION: The supraclavicular island flap is a rotational pedicled flap and
may have some advantages in head and neck reconstruction compared with free
tissue transfer when this kind of reconstruction is not affordable or
recommended. MATERIAL AND METHODS: We present our experience during the year 2016
in the application of the supraclavicular island flap in five cases as an
alternative to microvascular reconstruction in several defects after resection of
head and neck tumours. In two patients, the flap was used to close the surgical
pharyngostoma after total laryngectomy with partial pharyngectomy. In one
patient, it was used in lateral facial reconstruction after partial resection of
the temporal bone. In one case, it was used to close a skin defect after total
laryngectomy with prelaryngeal tissue extension. And in the last case to close a
neck skin defect after primary closure of a pharyngo-cutaneous fistula. There
were no flap complications, and the result was satisfactory in all cases.
RESULTS: The supraclavicular artery island flap is useful and versatile in head
and neck reconstruction. Operating room time in aged patients or those with
comorbidities will be reduced compared to free flaps. The surgical technique is
relatively easy and can be used for skin and mucosal coverage. CONCLUSION: The
supraclavicular island flap could be a recommended option in head and neck
reconstruction, its use seems to be increasing and provides a safe and time
saving option to free flaps in selected patients.
PMID- 28506449
TI - Improved growth, tolerance and intake with an extensively hydrolysed peptide feed
in infants with complex disease.
AB - BACKGROUND & AIMS: Infants with complex medical conditions often display
faltering growth due to elevated nutritional requirements, poor intake and
intolerance of feeding with malabsorption and maldigestion. As a result their
nutritional management can be extremely challenging and enteral nutritional
support is required. This study aimed to investigate the effectiveness, tolerance
and acceptability of nutritional support with a specially formulated, paediatric
peptide feed in infants with complex disease and signs of growth faltering with
their current nutritional management. METHODS: This prospective intervention
study investigated gastrointestinal (GI) tolerance, nutritional intake and
compliance with feeding, anthropometry and growth in 18 infants (mean age 6.11
months +/- 4.69, mean weight 4.97 kg +/- 1.71) during 28 days of enteral
nutritional support with a paediatric (1 kcal/ml) readymade peptide feed.
RESULTS: GI tolerance to nutritional support with a peptide enteral feed was good
and either improved or remained stable over the study. Compliance was excellent
(94.0% +/- 12.6), total energy intake improved (+23 +/- 42 kcal/kg, p = 0.037)
and mean weight (0.61 kg +/- 0.31, p = 0.0001), length (1.89 +/- 1.77 cm, p =
0.0001), head circumference (1.33 +/- 1.29 cm, p = 0.001), weight for length Z
score (p < 0.05), and weight for age Z score (p < 0.05) significantly improved.
Sixty one percent (n = 11) of the infants showed signs of increased growth
velocity, moving upwards in terms of their centiles. All 18 infants continued
with the paediatric, peptide enteral feed once the study was complete.
CONCLUSIONS: This prospective study showed that nutrition support with a
specially formulated, paediatric peptide readymade feed was well tolerated,
helped to promote growth, and can be considered suitable for use in infants with
complex disease and faltering growth who are unable to tolerate a whole protein
feed.
PMID- 28506451
TI - Motor skill development in low-income, at-risk preschoolers: A community-based
longitudinal intervention study.
AB - OBJECTIVES: This study aimed to: (1) determine the status of fundamental movement
skill (FMS) performance in low-income, at-risk preschoolers; and (2) evaluate the
impact of the Food Friends Get Movin' with Mighty Moves (MM) program on improving
children's FMS at two-year follow-up. DESIGN: Longitudinal, quasi-experimental
study with matched controls. METHODS: The Colorado LEAP study was conducted in
four Head Start/preschools (two intervention, two control) serving children aged
3-5 years. MM was delivered to the intervention group during preschool. The
Bruininks-Oseretsky Test of Motor Proficiency, Second Edition (BOT-2) subtests
for balance, running speed and agility, upper-limb coordination (object control
(OC) skills) and strength were administered to children at baseline, post
intervention in preschool, one-year follow-up (kindergarten), and two-year follow
up (first grade). RESULTS: Compared to the normative sample's mean, the mean
scaled score for all participants at baseline was significantly lower for balance
(p=0.016) and OC skills (p<0.001). At two-year follow-up, the means of balance
for all participants and OC skills for just the control group were significantly
lower than those of the normative sample (p<=0.001). Hierarchical linear
regression analyses revealed a significant intervention effect for OC skills with
the overall model accounting for 41% of variance at two-year follow-up,
F(6,165)=20.45, p<0.001. No intervention effects were found for the other three
BOT-2 subtests. CONCLUSIONS: Delivering the MM program in preschool confers a
lasting impact on FMS, specifically OC skills, in at-risk elementary school
children. Results suggest that at-risk preschoolers are already behind in FMS
development and these delays will continue through first grade.
PMID- 28506452
TI - Performing nuclear medicine examinations in pregnant women.
AB - The number of nuclear medicine examinations performed worldwide has been steadily
increasing over the last few years. By consequence, an ever increasing number of
pregnant women are likely to be exposed to radioisotopes. The range of doses
encountered in nuclear medicine practice is well below the threshold for
deterministic effects, such as embryonic death, birth defects or mental
retardation. According to the linear no-threshold hypothesis, however, stochastic
effects (e.g. an increased risk of cancer) remain possible even at this dose
range. This purely hypothetical radiation risk to the fetus should however be put
in perspective with the risk of having a scan of low diagnostic quality for a
life-threatening medical condition. In recent years there has been a push to
reduce as much as possible the dose from radiological imaging, for example by
using acquisition protocols specific to pregnant women and by injecting lower
activities. These approaches, in our opinion, overweigh the radiation risk and
actually may put the life of both the mother and the fetus in danger. Since
imaging protocols already seek to use the lowest possible dose compatible with a
quality scan for all patients, pregnant women should be imaged using the
protocols applied to any other patient. Encouraging bladder voiding by natural
means after injection will significantly reduce fetal exposure without
compromising image quality.
PMID- 28506453
TI - Challenges of dosimetry of ultra-short pulsed very high energy electron beams.
AB - Very high energy electrons (VHEE) in the range from 100 to 250MeV have the
potential of becoming an alternative modality in radiotherapy because of their
improved dosimetric properties compared with 6-20MV photons generated by clinical
linear accelerators (LINACs). VHEE beams have characteristics unlike any other
beams currently used for radiotherapy: femtosecond to picosecond duration
electron bunches, which leads to very high dose per pulse, and energies that
exceed that currently used in clinical applications. Dosimetry with conventional
online detectors, such as ionization chambers or diodes, is a challenge due to
non-negligible ion recombination effects taking place in the sensitive volumes of
these detectors. FLUKA and Geant4 Monte Carlo (MC) codes have been employed to
study the temporal and spectral evolution of ultrashort VHEE beams in a water
phantom. These results are complemented by ion recombination measurements
employing an IBA CC04 ionization chamber for a 165MeV VHEE beam. For comparison,
ion recombination has also been measured using the same chamber with a
conventional 20MeV electron beam. This work demonstrates that the IBA CC04
ionization chamber exhibits significant ion recombination and is therefore not
suitable for dosimetry of ultrashort pulsed VHEE beams applying conventional
correction factors. Further study is required to investigate the applicability of
ion chambers in VHEE dosimetry.
PMID- 28506454
TI - Esophageal intramural pseudodiverticulosis, a rare cause of stenosis.
PMID- 28506455
TI - Trauma morning report is the ideal environment to teach and evaluate resident
communication and sign-outs in the 80 hour work week.
AB - BACKGROUND: The 80h work week has raised concerns that complications may increase
due to multiple sign-outs or poor communication. Trauma Surgery manages complex
trauma and acute care surgical patients with rapidly changing physiology,
clinical demands and a large volume of data that must be communicated to render
safe, effective patient care. Trauma Morning Report format may offer the ideal
situation to study and teach sign-outs and resident communication. MATERIALS AND
METHODS: Surgery Residents were assessed on a 1-5 scale for their ability to
communicate to their fellow residents. This consisted of 10 critical points of
the presentation, treatment and workup from the previous night's trauma
admissions. Scores were grouped into three areas. Each area was scored out of 15.
Area 1 consisted of Initial patient presentation. Area 2 consisted of events in
the trauma bay. Area 3 assessed clarity of language and ability to communicate to
their fellow residents. The residents were assessed for inclusion of pertinent
positive and negative findings, as well as overall clarity of communication. In
phase 1, residents were unaware of the evaluation process. Phase 2 followed a
series of resident education session about effective communication, sign-out
techniques and delineation of evaluation criteria. Phase 3 was a resident-blinded
phase which evaluated the sustainability of the improvements in resident
communication. RESULTS: 50 patient presentations in phase 1, 200 in phase 2, and
50 presentations in phase 3 were evaluated. Comparisons were made between the
Phase 1 and Phase 2 evaluations. Area 1 (initial events) improved from 6.18 to
12.4 out of 15 (p<0.0001). Area 2 (events in the trauma bay) improved from 9.78
to 16.53 (p<0.0077). Area 3 (communication and language) improved from 8.36 to
12.22 out of 15 (P<0.001). Phase 2 to Phase 3 evaluations were similar, showing
no deterioration of skills. CONCLUSIONS: Trauma Surgery manages complex surgical
patients, with rapidly changing physiologic and clinical demands. Trauma Morning
Report, with diverse attendance including surgical attendings and residents in
various training years, is the ideal venue for real-time teaching and evaluation
of sign-outs and reinforcing good communication skills in residents.
PMID- 28506456
TI - Prevalence of Asymptomatic Coronary Heart Disease in the Siblings of Young
Myocardial Infarction Patients as Detected by Coronary Computer Tomography
Angiography: A Pilot Study.
AB - BACKGROUND: There is little data on the prevalence of coronary heart disease
(CHD) in the young. The study aimed to estimate the prevalence of asymptomatic
CHD in siblings of young patients with myocardial infarction (MI) using coronary
computed tomography angiography (CCTA). METHODS: Prospective observational data
was collected on siblings of patients aged <=55 years presenting with acute MI
and having coronary stenosis >=50% on invasive coronary angiography in at least
one epicardial coronary artery. Inclusion criteria included ages 30-55 and 30-60
years for males and females respectively. Outcome of interest was obstructive CHD
by coronary computer tomography angiography (CCTA), which was defined by either
moderate (50-69% stenosis) and/or severe (>=70% stenosis). RESULTS: Fifty
participants were studied of whom 20 (40%) were male. Thirty (60%) were current
or ex-smokers, 4 (8%) had diabetes, 8 (16%) had hypertension and 26 (52%) had
dyslipidaemia. Obstructive CHD by CCTA was detected in 9 (18%, 95% CI 9%-31%)
participants and 3 (6%, 95% CI 1%-17%) participants were found to have severe
luminal stenosis. The median radiation dose was 3.9 (IQR 0.9) mSv. CONCLUSIONS:
Approximately a fifth of siblings of young MI patients were found to have
asymptomatic but obstructive CHD detected on CCTA of which one third was severe.
This is a group in whom screening for CHD warrants further investigation.
PMID- 28506457
TI - Early Thrombosis and Non-Heparin-Coated Pulmonary Artery Catheters.
PMID- 28506458
TI - Impact of Postoperative Hypothermia on Outcomes in Coronary Artery Bypass Surgery
Patients.
AB - OBJECTIVES: To determine the impact of postoperative hypothermia on outcomes in
coronary artery bypass graft surgery (CABG) patients. DESIGN: A retrospective
study was performed on patients who underwent isolated CABG between 2011 and
2014. SETTING: Single-center study at a university hospital. PARTICIPANTS: All
patients who underwent isolated CABG with cardiopulmonary bypass between 2011 and
2014. INTERVENTIONS: Patients underwent isolated CABG on cardiopulmonary bypass.
MEASUREMENTS AND MAIN RESULTS: Patients were propensity-score matched based on
the likelihood of being hypothermic (<36oC) or normothermic (>=36oC) on arrival
to the cardiac surgery intensive care unit (ICU) from the operating room. Total
transfusion requirements, composite in-hospital morbidity and/or mortality
endpoint, total hours in the ICU, and length of hospital stay were compared
between the 2 groups. Of the 1,030 patients undergoing isolated CABG, 529 (51.3%)
were hypothermic on arrival to the ICU. The hypothermic cohort were older, had
more females, had lower body mass indices, had lower starting hematocrit values,
were cooled to lower temperatures while on cardiopulmonary bypass, and had longer
cardiopulmonary bypass runs compared with the normothermic group. Of the 748
patients who were propensity matched, there were no differences in blood and
blood product transfusion requirements, mortality and complication rates, time on
the ventilator, length of ICU stay, and length of hospital stay between
hypothermic and normothermic patients. CONCLUSIONS: Hypothermia at ICU admission
after CABG was not associated with increased adverse outcomes, possibly
suggesting that complete rewarming before separation from cardiopulmonary bypass
may not be essential in all patients.
PMID- 28506459
TI - Increased Mitral Gradient After Transcatheter Aortic Valve Replacement: Is It
Anatomic Mitral Valve Obstruction Or Related to Hemodynamics?
PMID- 28506460
TI - Mechanisms of Ubiquitin-Nucleosome Recognition and Regulation of 53BP1 Chromatin
Recruitment by RNF168/169 and RAD18.
AB - The protein 53BP1 plays a central regulatory role in DNA double-strand break
repair. 53BP1 relocates to chromatin by recognizing RNF168-mediated mono
ubiquitylation of histone H2A Lys15 in the nucleosome core particle dimethylated
at histone H4 Lys20 (NCP-ubme). 53BP1 relocation is terminated by ubiquitin
ligases RNF169 and RAD18 via unknown mechanisms. Using nuclear magnetic resonance
(NMR) spectroscopy and biochemistry, we show that RNF169 bridges ubiquitin and
histone surfaces, stabilizing a pre-existing ubiquitin orientation in NCP-ubme to
form a high-affinity complex. This conformational selection mechanism contrasts
with the low-affinity binding mode of 53BP1, and it ensures 53BP1 displacement by
RNF169 from NCP-ubme. We also show that RAD18 binds tightly to NCP-ubme through a
ubiquitin-binding domain that contacts ubiquitin and nucleosome surfaces accessed
by 53BP1. Our work uncovers diverse ubiquitin recognition mechanisms in the
nucleosome, explaining how RNF168, RNF169, and RAD18 regulate 53BP1 chromatin
recruitment and how specificity can be achieved in the recognition of a ubiquitin
modified substrate.
PMID- 28506461
TI - MK2 Phosphorylates RIPK1 to Prevent TNF-Induced Cell Death.
AB - TNF is an inflammatory cytokine that upon binding to its receptor, TNFR1, can
drive cytokine production, cell survival, or cell death. TNFR1 stimulation causes
activation of NF-kappaB, p38alpha, and its downstream effector kinase MK2,
thereby promoting transcription, mRNA stabilization, and translation of target
genes. Here we show that TNF-induced activation of MK2 results in global RIPK1
phosphorylation. MK2 directly phosphorylates RIPK1 at residue S321, which
inhibits its ability to bind FADD/caspase-8 and induce RIPK1-kinase-dependent
apoptosis and necroptosis. Consistently, a phospho-mimetic S321D RIPK1 mutation
limits TNF-induced death. Mechanistically, we find that phosphorylation of S321
inhibits RIPK1 kinase activation. We further show that cytosolic RIPK1
contributes to complex-II-mediated cell death, independent of its recruitment to
complex-I, suggesting that complex-II originates from both RIPK1 in complex-I and
cytosolic RIPK1. Thus, MK2-mediated phosphorylation of RIPK1 serves as a
checkpoint within the TNF signaling pathway that integrates cell survival and
cytokine production.
PMID- 28506462
TI - A Slow Conformational Switch in the BMAL1 Transactivation Domain Modulates
Circadian Rhythms.
AB - The C-terminal transactivation domain (TAD) of BMAL1 (brain and muscle ARNT-like
1) is a regulatory hub for transcriptional coactivators and repressors that
compete for binding and, consequently, contributes to period determination of the
mammalian circadian clock. Here, we report the discovery of two distinct
conformational states that slowly exchange within the dynamic TAD to control
timing. This binary switch results from cis/trans isomerization about a highly
conserved Trp-Pro imide bond in a region of the TAD that is required for normal
circadian timekeeping. Both cis and trans isomers interact with transcriptional
regulators, suggesting that isomerization could serve a role in assembling
regulatory complexes in vivo. Toward this end, we show that locking the switch
into the trans isomer leads to shortened circadian periods. Furthermore,
isomerization is regulated by the cyclophilin family of peptidyl-prolyl
isomerases, highlighting the potential for regulation of BMAL1 protein dynamics
in period determination.
PMID- 28506463
TI - RNA Pol II Dynamics Modulate Co-transcriptional Chromatin Modification, CTD
Phosphorylation, and Transcriptional Direction.
AB - Eukaryotic genes are marked by conserved post-translational modifications on the
RNA pol II C-terminal domain (CTD) and the chromatin template. How the 5'-3'
profiles of these marks are established is poorly understood. Using pol II
mutants in human cells, we found that slow transcription repositioned specific co
transcriptionally deposited chromatin modifications; histone H3 lysine 36
trimethyl (H3K36me3) shifted within genes toward 5' ends, and histone H3 lysine 4
dimethyl (H3K4me2) extended farther upstream of start sites. Slow transcription
also evoked a hyperphosphorylation of CTD Ser2 residues at 5' ends of genes that
is conserved in yeast. We propose a "dwell time in the target zone" model to
explain the effects of transcriptional dynamics on the establishment of co
transcriptionally deposited protein modifications. Promoter-proximal Ser2
phosphorylation is associated with a longer pol II dwell time at start sites and
reduced transcriptional polarity because of strongly enhanced divergent antisense
transcription at promoters. These results demonstrate that pol II dynamics help
govern the decision between sense and divergent antisense transcription.
PMID- 28506466
TI - Impaired steroidogenesis in the testis of leptin-deficient mice (ob/ob -/-).
AB - The obesity and its comorbidities, including resistance to leptin, impacts the
reproductive function. Testes express leptin receptors in the germ cells and
Leydig cells. Then, leptin-deficient animals are obese and infertile. We aimed to
evaluate the structure and steroidogenic pathway of the testis of deficient
leptin mice. Three months old male C57BL/6 mice (wild-type, WT) and deficient
leptin (ob/ob) mice had their testes dissected and prepared for analyses.
Compared to the WT group, the ob/ob group showed a greater body mass with smaller
testes, and alterations in the germinative epithelium: fewer spermatogonia,
spermatocytes, and spermatids. The Sertoli cells and the germ cells showed
condensed nuclei and nuclear fragmentation indicating cell death, in agreement
with a low expression of the proliferating cell nuclear antigen and a high
expression of Caspase3. In the ob/ob group, the sperm was absent in the
seminiferous tubules, and the steroidogenic pathway was compromised (low 3Beta
hydroxysteroid dehydrogenase and steroidogenic acute regulatory protein).
Further, all hormone receptors involved in the testicular function were down
expressed (androgen, estrogen, follicle-stimulating, luteinizing, aromatase, and
nicotinamide adenine dinucleotide phosphate). In conclusion, the findings
indicate significant morphological, hormonal and enzymatic changes in the testis
of the ob/ob mice. The shifts in the enzymatic steroidogenic pathway and the
enzymes related to spermatic activity support the insights about the failures in
the fertility of these animals. The study provides new evidence and contributes
to the understanding of how the lack of leptin and obesity might negatively
modulate the testicular function leading to infertility.
PMID- 28506464
TI - Recruited Monocytes and Type 2 Immunity Promote Lung Regeneration following
Pneumonectomy.
AB - To investigate the role of immune cells in lung regeneration, we used a
unilateral pneumonectomy model that promotes the formation of new alveoli in the
remaining lobes. Immunofluorescence and single-cell RNA sequencing found CD115+
and CCR2+ monocytes and M2-like macrophages accumulating in the lung during the
peak of type 2 alveolar epithelial stem cell (AEC2) proliferation. Genetic loss
of function in mice and adoptive transfer studies revealed that bone marrow
derived macrophages (BMDMs) traffic to the lung through a CCL2-CCR2 chemokine
axis and are required for optimal lung regeneration, along with Il4ra-expressing
leukocytes. Our data suggest that these cells modulate AEC2 proliferation and
differentiation. Finally, we provide evidence that group 2 innate lymphoid cells
are a source of IL-13, which promotes lung regeneration. Together, our data
highlight the potential for immunomodulatory therapies to stimulate
alveologenesis in adults.
PMID- 28506469
TI - Sur la vitesse d'extinction d'une population dans un environnement aleatoire.
AB - This study focuses on the speed of extinction of a population living in a random
environment that follows a continuous-time Markov chain. Each individual dies or
reproduces at a rate that depends on the environment. The number of offspring
during reproduction follows a given probability law that also depends on the
environment. In the so-called subcritical case where the population goes for sure
to extinction, there is an explicit formula for the speed of extinction. In some
sense, environmental stochasticity slows down population extinction.
PMID- 28506467
TI - Apoptosis of bovine granulosa cells: Intracellular pathways and differentiation.
AB - Follicular atresia in granulosa and theca cells occurs by apoptosis through weak
hormonal stimulation. We have previously proposed an in vitro model to study this
process by inducing apoptosis in BGC-1, a bovine granulosa cell line, and in
primary cultures from ovaries with or without corpus luteum (CPGB+ and CPGB-,
respectively), with different doses of gonadotropin releasing hormone (GnRH)
analogs (leuprolide acetate (LA) as agonist and antide as antagonist). BGC-1
represent immature granulosa cells, whereas CPGB represent different degrees of
luteinization. Our aim was to evaluate the intracellular pathways involved in the
GnRH regulation of apoptosis in BGC-1. Treatment with LA 100nM but not with
antide led to an increase in BAX over BCL-2 expression, showing antagonism of
antide. All treatments inhibited phospholipase-D (PLD) activity compared to
control, implying agonist behavior of antide. Progesterone in vitro production
and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) expression revealed different
degrees of luteinization: BGC-1 were immature, whereas CPGB+ were less
differentiated than CPGB-. We concluded that LA-induced apoptosis in BGC-1 occurs
by activation of the mitochondrial pathway and by inhibition of PLD activity and
that antide might work both as an antagonist of the intrinsic pathway and as an
agonist of the extrinsic protection pathway by inhibiting PLD activity.
PMID- 28506468
TI - [Impact of cork oak management on the ectomycorrhizal fungal diversity associated
with Quercus suber in the Maamora forest (Morocco)].
AB - The cork oak forest is an ecosystem playing a major role in Moroccan socio
economy and biodiversity conservation. However, this ecosystem is negatively
impacted by extensive human- and climate-driven pressures, causing a strong
decrease in its distribution and a worsening of the desertification processes.
This study aims at characterising the impact of cork oak forest management on a
major actor of its functioning, the ectomycorrhizal (EcM) fungal community
associated with Quercus suber, and the determination of EcM bio-indicators. The
EcM fungal community has been monitored during spring and winter seasons in two
sites of the Moroccan Maamora forest, corresponding to a forest site either
impacted by human activities or protected. A significant impact of cork oak
forest management on the EcM fungal community has been revealed, with major
differences during the summer season. The results confirmed the potential
ecological significance of several EcM fungi (e.g., Cenococcum) in the
sustainability of the cork oak forest functioning, but also the significant
association of certain EcM fungi (Pachyphloeus, Russula, Tomentella) with a
perturbation or a season, and consequently to the cork oak forest status or to
climatic conditions, respectively. The development of study at the Mediterranean
scale may improve the robustness of ecological models to predict the impact of
global changes on this emblematic ecosystem of Mediterranean basin.
PMID- 28506465
TI - Deconstructing Olfactory Stem Cell Trajectories at Single-Cell Resolution.
AB - A detailed understanding of the paths that stem cells traverse to generate mature
progeny is vital for elucidating the mechanisms governing cell fate decisions and
tissue homeostasis. Adult stem cells maintain and regenerate multiple mature cell
lineages in the olfactory epithelium. Here we integrate single-cell RNA
sequencing and robust statistical analyses with in vivo lineage tracing to define
a detailed map of the postnatal olfactory epithelium, revealing cell fate
potentials and branchpoints in olfactory stem cell lineage trajectories.
Olfactory stem cells produce support cells via direct fate conversion in the
absence of cell division, and their multipotency at the population level reflects
collective unipotent cell fate decisions by single stem cells. We further
demonstrate that Wnt signaling regulates stem cell fate by promoting neuronal
fate choices. This integrated approach reveals the mechanisms guiding olfactory
lineage trajectories and provides a model for deconstructing similar hierarchies
in other stem cell niches.
PMID- 28506470
TI - Coronary CT angiography in the emergency department utilizing second and third
generation dual source CT.
AB - BACKGROUND: Coronary computed tomography angiography (coronary CTA) allows
efficient triage of low to intermediate risk patients with suspected acute
coronary syndrome (ACS) in the emergency department (ED). Techniques for coronary
CTA acquisition in the ED continue to evolve with the establishment of
standardized scan protocols and the introduction of newer generations of CT
hardware. OBJECTIVES: To evaluate qualitative and quantitative image quality and
radiation dose exposure of coronary CTA acquired on 2nd versus 3rd generation
dual source CT (DSCT) scanners using a standardized institutional scan protocol
designed for the ED. METHODS: A retrospective observational case-control study
was performed of 246 ED patients referred to coronary CTA with suspicion of ACS
(56.5% male; mean age 53.3 +/- 11.6 years) between October 2013 and August
2015.123 consecutive patients were scanned on 3rd generation DSCT, and a cohort
of 123 patients matched by age, BMI and heart rate were identified who had
undergone 2nd generation DSCT imaging utilizing the same standard clinical
protocol. Qualitative and quantitative image quality parameters and radiation
exposures were evaluated. RESULTS: Qualitative image quality was significantly
higher using 3rd generation DSCT as compared to 2nd generation (p < 0.001). Mean
attenuation in the proximal coronary arteries was also significantly higher on
3rd generation DSCT than for 2nd generation (586 HU vs. 426 HU in the left main
coronary artery (LM), p < 0.001). Signal-to-noise ratio (SNR) and contrast-to
noise ratio (CNR) values, however, were lower in 3rd generation DSCT than 2nd
generation (SNR 11.2 [9.9-13.4] vs 13.5 [11.0-15.5] and CNR 12.4 [10.9-14.8] vs
15.2 [12.8-17.9] in the LM, p < 0.001). Median effective dose was also lower for
3rd generation DSCT than for 2nd generation (2.9 [2.3-5.0] mSv and 3.7 mSv [2.5
5.7], respectively) although this trend did not reach statistical significance (p
= 0.065). CONCLUSION: Qualitative image quality and mean CT attenuation values of
the assessed coronary segments were significantly higher using 3rd generation
DSCT. SNR and CNR were lower on 3rd generation DSCT, however this was accompanied
by a trend toward lower radiation dose exposure when using the same standard
institutional protocol.
PMID- 28506472
TI - Gadolinium accumulation after contrast-enhanced magnetic resonance imaging: Which
implications in patients with Crohn's disease?
AB - Crohn's disease (CD) is a chronic inflammatory condition of the bowel,
characterized by an alternation of remission and relapse phases, leading to a
progressive intestinal damage with loss of function. Magnetic resonance
enterography has been widely used in the past for the evaluation of fistulizing
disease, but its use increased over time, being considered helpful in different
moments of disease course. Intravenous injection of Gadolinium-based contrast
agents has been demonstrated to be crucial to assess mucosal inflammation,
transmural involvement, and extraintestinal disease. Recently, Gadolinium
accumulation in human tissues has been increasingly reported, although clinical
implications of this event are still unclear. In the present paper, we review the
main evidence on the topic, focusing on the potential implications for
gastroenterological practice.
PMID- 28506473
TI - [Congenital lamellar cataract].
PMID- 28506471
TI - Genetics of gonadotropins and their receptors as markers of ovarian reserve and
response in controlled ovarian stimulation.
AB - Several controlled ovarian stimulation (COS) protocols have been developed to
increase the yield of mature oocytes retrieved in assisted reproductive
techniques (ARTs). The ovarian reserve (OR) influences the COS response, and it
represents the main parameter that helps clinicians in refining clinical
treatments in the perspective of a "personalized" ART. This approach is even more
needed in particular conditions such as poor OR or polycystic ovary syndrome.
Follicle-stimulating hormone, luteinizing hormone, and human chorionic
gonadotropin are currently used in COS at different combinations and with
different efficacies, even if the best approach definition is controversial.
Differences in individual-specific ovarian response to gonadotropin stimulation
can be due to alterations of genes encoding for hormones or their receptors. In
particular, FSHB c.-211G>T, FSHR p.Asn680Ser, and c.-29G>A SNP allelic
combinations may be used as OR and COS response markers. The purpose of this
review is to highlight the evidence-based relevance of mutations and
polymorphisms in gonadotropins and their receptor genes as predictive markers of
OR and COS response to achieve fine-tuned therapeutic regimens.
PMID- 28506474
TI - [Retinal inner nuclear layer microcysts on spectral-domain OCT in alcoholic optic
neuropathy].
PMID- 28506475
TI - A novel perfused porcine simulator for teaching aortic anastomosis increases
resident interest in vascular surgery.
AB - OBJECTIVE: This report describes a novel simulator, euthanized pigs on
cardiopulmonary bypass, and validates this simulator with a controlled trial in
general surgery residents learning aortic anastomosis. We evaluated this novel
simulator with the following hypothesis: our porcine perfused simulator is as
good as or better than the standard rubber tubing, low-fidelity models used for
vascular anastomotic training. METHODS: Euthanized pigs were placed on
cardiopulmonary bypass, creating a perfused, ex vivo model on which to perform
surgical procedures. The participants in the study were postgraduate year 2, 3,
and 4 general surgery residents. Residents were randomized to practice aortic
anastomosis in the pig laboratory (PL) simulator or in a dry laboratory. The PL
residents and control residents performed a first vascular anastomosis on the
rubber tube model. Anastomosis creation was filmed. The anastomosis and video
were stored for later grading. Next, all residents underwent an ungraded, one-on
one training session with the attending vascular surgeon. After the training
session, all residents completed a second videotaped rubber tubing anastomosis.
The grading scales used were validated by other authors: Global Assessment Score,
Final Product Score, and Checklist Scoring Instrument. Survey data describing
this experience were collected using a 13-question prelaboratory and 16-question
postlaboratory questionnaires consisting of yes/no, multiple selection, and 5
point Likert-type scale questions. RESULTS: All residents had a statistically
significant improvement in time to completion and in the Global Assessment Score
with tutored practice. The PL residents showed statistically significant
improvement in completion time between the first and second videotaped
anastomosis; however, there was no statistically significant improvement in the
scoring metrics. The control residents showed statistically significant
improvement in all three scoring metrics, but no statistically significant
difference was found in completion time. The survey data showed a statistically
significant shift in considering vascular surgery as a career after the
experience in the PL group (P = .05) compared with the control group, who had no
change in interest (P = .91). CONCLUSIONS: Our prospective, randomized clinical
trial shows that the porcine cardiopulmonary bypass model achieves similar
results to a previously validated bench top model while improving general surgery
resident interest in vascular surgery as a career.
PMID- 28506476
TI - Adherence to lipid management guidelines is associated with lower mortality and
major adverse limb events in patients undergoing revascularization for chronic
limb-threatening ischemia.
AB - OBJECTIVE: The 2013 American College of Cardiology/American Heart Association
lipid management guidelines recommend high-intensity statins for all patients
<=75 years old with chronic limb-threatening ischemia (CLTI) and moderate
intensity statins for CLTI patients >75 years old without contraindications or on
dialysis, but these recommendations are based primarily on coronary and stroke
data. We aimed to validate these guidelines in patients with CLTI and to assess
current adherence to these recommendations. METHODS: We identified all patients
with CLTI who underwent first-time revascularization (endovascular or surgical)
at Beth Israel Deaconess Medical Center from 2005 to 2014. Patients were
classified as taking high-intensity, moderate-intensity, low-intensity, or no
statin postoperatively. Outcomes included death and major adverse limb event
(MALE). Propensity scores were calculated for the probability of receiving
guideline-recommended intensity of statin therapy to account for nonrandom
assignment of treatments. Cox regression models were constructed and adjusted for
the propensity scores and further adjusted for strong potential confounders.
RESULTS: After excluding patients on hemodialysis (n = 252), we identified 1019
limbs from 931 patients with a median follow-up of 380 days. Patients discharged
on the recommended statin intensity had higher rates of preoperative statin use,
coronary artery disease, chronic kidney disease, stroke, atrial fibrillation,
congestive heart failure, and coronary artery bypass grafting; they had lower
smoking rates and were less likely to be ambulatory preoperatively. Overall, only
35% were taking the recommended statin dosage: 55% of those >75 years old and 20%
of those <=75 years old. In multivariable analysis including propensity scores
where appropriate, discharge on any statin was associated with lower mortality
(hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.60-0.90; P < .01).
Discharge on the recommended intensity of statin therapy was associated with
lower mortality (HR, 0.73; 95% CI, 0.60-0.99; P < .05) and lower MALE rate (HR,
0.71; 95% CI, 0.51-0.97; P < .05). Patients >75 years old and <=75 years old
accrued similar benefit. In patients >75 years old, moderate-intensity statin
therapy was associated with lower rates of death and MALE compared with high
intensity therapy but did not reach statistical significance. CONCLUSIONS: Use of
the recommended intensity of statin therapy in compliance with 2013 American
College of Cardiology/American Heart Association lipid management guidelines is
associated with significantly improved survival and lower MALE rate in patients
undergoing revascularization for CLTI. Adherence to current guidelines is an
appealing target for quality improvement.
PMID- 28506479
TI - The spectrum and management of noniatrogenic vascular trauma in the pediatric
population.
AB - BACKGROUND: To describe the spectrum of noniatrogenic pediatric vascular injuries
and their outcomes at a large tertiary pediatric hospital. METHODS: Retrospective
review of a prospectively-maintained trauma database, identifying children with
noniatrogenic vascular injuries managed between 1994 and 2014. RESULTS: A total
of 198 patients were identified. Those patients with a digital or intracerebral
vascular injury (92/198) were excluded from further analysis. The remaining 106
patients represented 1.2% of all traumas managed at our institution during the 21
year study period. The majority were male (75%), and between 1 and 12years of age
(71% of all patients). Median time from trauma scene to any hospital was 48min
(range 0-132), and most patients were transferred from another hospital (64%).
Three patients were declared dead upon arrival (3%). Penetrating injuries
accounted for most injuries (72%), while blunt injuries accounted for the
remainder. Ulnar, radial, or brachial artery trauma accounted for 47% of
injuries. Most vessels were treated operatively, by primary repair (49%), vessel
ligation (15%), or interposition graft (12%). Fourteen patients (13%) were
managed nonoperatively and most patients (74%) experienced no complications in
hospital or during follow-up. CONCLUSION: Noniatrogenic pediatric vascular
injuries are rare and represent a highly heterogeneous population. Most children
recover well, with minimal perioperative complications. LEVEL OF EVIDENCE: IV
(case series with no comparison group).
PMID- 28506478
TI - Metformin treatment does not affect the risk of ruptured abdominal aortic
aneurysms.
AB - OBJECTIVE: Diabetes counteracts formation and rupture of abdominal aortic
aneurysms, possibly through arterial matrix accumulation. Use of metformin, on
the other hand, reduces arterial accumulation of matrix molecules. Consequently,
we hypothesized that metformin treatment may reverse the protective role of
diabetes on the development and course of aneurysms, that is, that metformin
would be associated with aneurysm rupture among individuals with diabetes.
METHODS: Using nationwide Danish registry data, we performed a nested case
control study on the association between long-term use of metformin and ruptured
abdominal aortic aneurysm (RAAA). The source population was defined as all
individuals in Denmark with diabetes. Cases were all individuals within the
source population who were hospitalized with a primary diagnosis of RAAA. For
each case, 10 controls matched by age and sex were randomly selected from the
source population by risk set sampling. The main exposure measure was a
cumulative dispensing of 1000 g of metformin between January 1995 and the index
date. RESULTS: We identified 362 cases of RAAA during 1998 to 2013, of which
83.7% occurred in men with a median age of 74 years. In total, 22.4% of the case
population were long-term metformin users compared with 28.8% of the controls. We
found a statistically nonsignificant protective effect of long-term metformin use
toward RAAA with crude odds ratio (OR) of 0.74 (confidence interval, 0.54-1.00).
When adjusted for covariates, OR increased to 0.84 (confidence interval, 0.61
1.17). None of the subgroups had ORs deviating substantially from the main
result. CONCLUSIONS: Metformin use does not increase the risk of RAAA among
individuals with diabetes.
PMID- 28506477
TI - Medical therapy and intervention do not improve uncomplicated isolated mesenteric
artery dissection outcomes over observation alone.
AB - OBJECTIVE: Isolated dissection of the mesenteric vessels is rare but increasingly
recognized. This study aimed to evaluate patient characteristics, primary
treatment, and subsequent outcomes of mesenteric dissection using multi
institutional data. METHODS: All patients at participant hospitals between
January 2003 and December 2015 with dissection of the celiac artery (or its
branches) or dissection of the superior mesenteric artery (SMA) were included.
Patients with an aortic dissection were excluded. Demographic, treatment, and
follow-up data were collected. The primary outcomes included late vessel
thrombosis (LVT) and aneurysmal degeneration (AD). RESULTS: Twelve institutions
identified 227 patients (220 with complete treatment records) with a mean age of
55 +/- 12.5 years. Median time to last follow up was 15 months (interquartile
range, 3.8-32). Most patients were men (82% vs 18% women) and symptomatic at
presentation (162 vs 65 asymptomatic). Isolated SMA dissection was more common
than celiac artery dissection (n = 158 and 81, respectively). Concomitant
dissection of both arteries was rare (n = 12). The mean dissection length was
significantly longer in symptomatic patients than in asymptomatic patients in
both the celiac artery (27 vs 18 mm; P = .01) and the SMA (64 vs 40 mm; P <
.001). Primary treatment was medical in 146 patients with oral anticoagulation or
antiplatelet therapy (n = 76 and 70, respectively), whereas 56 patients were
observed. LVT occurred in six patients, and 16 patients developed AD (3% and 8%,
respectively). For symptomatic patients without evidence of ischemia (n = 134),
there was no difference in occurrence of LVT with medical therapy compared with
observation alone (9% vs 0%; P = .35). No asymptomatic patient (n = 64) had an
episode of LVT at 5 years. AD rates did not differ among symptomatic patients
without ischemia treated with medical therapy or observed (9% vs 5%; P = .95).
Surgical or endovascular intervention was performed in 18 patients (3 ischemia,
13 pain, 1 AD, 1 asymptomatic). Excluding the patients treated for ischemia,
there was no difference in LVT with surgical intervention vs medical management
(one vs five; P = .57). CONCLUSIONS: Asymptomatic patients with isolated
mesenteric artery dissection may be observed and followed up with intermittent
imaging. Symptomatic patients tend to have longer dissections than asymptomatic
patients. Symptomatic isolated mesenteric artery dissection without evidence of
ischemia does not require anticoagulation and may be treated with antiplatelet
therapy or observation alone.
PMID- 28506481
TI - Peri- and intraoperative cognitive and language assessment for surgical resection
in brain eloquent structures.
AB - Neuropsychological care of patients suffering from an infiltrative glioma and
candidates for a neurosurgery under awake condition with intraoperative
functional mapping is a critical and mandatory stage in therapeutic management.
It enables to estimate the functional impact of the tumor and, consequently, the
efficacy of functional reorganization typically observed in these patients, not
only to better predict surgery outcomes and select appropriate tasks for
intraoperative functional mapping, but also to plan efficient and individualized
postoperative cognitive rehabilitation strategies. Neuropsychological care
management also enables patients to benefit from a solid psychological
preparation both to the surgery and its associated transitory functional
consequences, as well as provide a personalized psychological and emotional long
term support. Based on their solid experience in the peri-operative care of
diffuse low-grade glioma patients, the authors thoroughly describe the different
stages of neuropsychological management. Cognitive, emotional and language
assessments typically used by the authors around and during surgery are reported,
and different possible avenues of improvement are further discussed.
PMID- 28506480
TI - The epidemiology of inpatient pediatric trauma in United States hospitals 2000 to
2011.
AB - BACKGROUND: This study provides important updates to the epidemiology of
pediatric trauma in the United States. METHODS: Age-specific epidemiologic
analysis of the Healthcare Cost and Utilization Project's Nationwide Inpatient
Sample, representing 2.4 million pediatric traumatic injury discharges in the US
from 2000 to 2011. We present yearly data with overlying loess smoothing lines,
proportions of common injuries and surgical procedures, and survey-adjusted
logistic regression analysis. RESULTS: From 2000 to 2011 there was a 21.7%
decline in US pediatric trauma injury inpatient discharges from 273.2 to 213.7
admissions per 100,000. Inpatient case-fatality decreased 5.5% from 1.26% (95% CI
1.05-1.47) to 1.19% (95% CI 1.01-1.38). Severe injuries accounted for 26.5%
(se=0.11) of all discharges in 2000 increasing to 31.3% (se=0.13) in 2011. The
most common injury mechanism across all age groups was motor vehicle crashes
(MVCs), followed by assaults (15-19years), sports (10-14), falls (5-9) and burns
(<5). The total injury-related, inflation-adjusted cost was $21.7 billion,
increasing 56% during the study period. CONCLUSIONS: The overall rate of
inpatient pediatric injury discharges across the United States has been
declining. While injury severity is increasing in hospitalized patients, case
fatality rates are decreasing. MVCs remain a common source of all pediatric
trauma. LEVELS OF EVIDENCE: Level III.
PMID- 28506482
TI - Technical principles of direct bipolar electrostimulation for cortical and
subcortical mapping in awake craniotomy.
AB - INTRODUCTION: Intraoperative application of electrical current to the brain is a
standard technique during brain surgery for inferring the function of the
underlying brain. The purpose of intraoperative functional mapping is to reliably
identify cortical areas and subcortical pathways involved in eloquent functions,
especially motor, sensory, language and cognitive functions. MATERIAL AND
METHODS: The aim of this article is to review the rationale and the
electrophysiological principles of the use of direct bipolar electrostimulation
for cortical and subcortical mapping under awake conditions. RESULTS: Direct
electrical stimulation is a window into the whole functional network that
sustains a particular function. It is an accurate (spatial resolution of about
5mm) and a reproducible technique particularly adapted to clinical practice for
brain resection in eloquent areas. If the procedure is rigorously applied, the
sensitivity of direct electrical stimulation for the detection of cortical and
subcortical eloquent areas is nearly 100%. The main disadvantage of this
technique is its suboptimal specificity. Another limitation is the identification
of eloquent areas during surgery, which, however, could have been functionally
compensated postoperatively if removed surgically. CONCLUSION: Direct electrical
stimulation is an easy, accurate, reliable and safe invasive technique for the
intraoperative detection of both cortical and subcortical functional brain
connectivity for clinical purpose. In our opinion, it is the optimal technique
for minimizing the risk of neurological sequelae when resecting in eloquent brain
areas.
PMID- 28506483
TI - Cortical and subcortical functional neuroanatomy for low-grade glioma surgery.
AB - Knowledge of the encephalon anatomy is crucial for neurosurgical practice,
especially the main cortical functional structures and their connections. General
organisation of the encephalon is presented with frontal, parietal, occipital,
temporal, limbic and insular lobes and their Brodmann correspondence. Secondly,
subcortical anatomy will be presented with main white matter fasciculi in three
separated categories: association, commissural and projection fibers. Main
association fibers are inferior occipitofrontal fasciculus, superior longitudinal
fasciculus, arcuate fasciculus, inferior longitudinal fasciculus, uncinate
fasciculus, and cingulum. Commissural fibers include anterior commissure, corpus
callosum and fornix. Projection fibers are internal capsule and optic radiations.
PMID- 28506484
TI - A surgical approach to the anatomo-functional structure of language.
AB - INTRODUCTION: Language is the most widely mapped cognitive function during brain
surgery. Intraoperative language functional mapping using direct electrical
stimulation under awake conditions is currently the gold standard technique for
establishing the causal link between an area and a deficit that would be caused
by its resection. It is also a powerful tool to investigate the anatomical
correlates of current neuropsychological models of language. MATERIAL AND
METHODS: The aim of this article is to reexamine the anatomo-functional structure
of language that could be inferred from data obtained in direct electrical
stimulation studies during awake surgery. RESULTS: Concomitantly with the
development of new neuropsychological models of language, major advances have
been made in our understanding of error patterns elicited by language network
stimulation, both cortically and axonally. Following the recognition of visual
information, the language network of picture naming is organized in parallel into
two main dorsal phonological and ventral semantic subsystems that are sustained
anatomically by two systems (arcuate fasciculus and inferior fronto
occipital/inferior longitudinal/uncinate fasciculus respectively). Networks of
articulatory and motor aspects of speech are now better depicted (aslant tract,
third branch of longitudinal fasciculus). Finally, the links between the core
language networks and the cognitive control networks are also emerging.
CONCLUSION: Mastering the language map and its dynamical properties should be a
basic prerequisite for any neurosurgeon who wishes to operate on the brain with
the aim of optimizing the extent of resection while preserving language
abilities.
PMID- 28506485
TI - Surgery for dysembryoplastic neuroepithelial tumors and gangliogliomas in
eloquent areas. Functional results and seizure control.
AB - INTRODUCTION: Dysembryoplastic neuroepithelial tumors and gangliogliomas are
developmental glioneuronal tumors usually revealed by partial epilepsy. High
epileptogenicity, childhood epilepsy onset, drug-resistance, temporal location,
and seizure freedom after complete resection are common characteristics of both
tumors. We report the specificity of surgical management, functional results and
seizure outcome in cases of a tumor location in eloquent areas. METHODS: Among
150 patients (88 males, 3-55 years) operated on for refractory epilepsy due to a
glioneuronal tumor (1990-2015), 30 (20%, dysembryoplastic neuroepithelial
tumors=21; gangliogliomas=9) had a tumor located in an eloquent cortex (sensory
motor, insular or language areas). Surgery was performed after a preoperative
work-up, including stereo-electroencephalography in 48 patients (26%) and
functional MRI in 100 (67%). MRI-guided lesionectomy was mainly performed in
extra-temporal location, whereas an additional corticectomy was performed in a
temporal location. Tumor microsurgical resections were guided using
neuronavigation and cortical/subcortical electrical stimulations. Multiple
stereotactic thermocoagulations were performed in two insular tumors. RESULTS:
New motor/language deficits related to eloquent areas occurred postoperatively in
6/30 patients (20%) without any major permanent disability. Minor sensorimotor
(n=2) and moderate language disturbance (n=1) persisted in three of them.
Postoperative seizure-free outcome (mean follow-up>5 years) was obtained in 81%
of the entire series, but significantly decreased to 60% in eloquent areas.
Incomplete tumor resection was the main cause of surgical failure. However,
unfavorable seizure outcome was also observed despite complete tumor resection.
Malignant transformation occurred in one ganglioglioma. CONCLUSION: Epilepsy
surgery for benign glioneuronal tumors in eloquent areas provides acceptable
results regarding the functional risks. Complete tumor resection is crucial for
long-term favorable outcome.
PMID- 28506486
TI - Preoperative and intraoperative neurophysiological investigations for surgical
resections in functional areas.
AB - Brain regions are removed to treat lesions, but great care must be taken not to
disturb or remove functional areas in the lesion and in surrounding tissue where
healthy and diseased cells may be intermingled, especially for infiltrating
tumors. Cortical functional areas and fiber tracts can be localized
preoperatively by probabilistic anatomical tools, but mapping of functional
integrity by neurophysiology is essential. Identification of the primary motor
cortex seems to be more effectively performed with transcranial magnetic
stimulation (TMS) than functional magnetic resonance imaging (fMRI). Language
area localization requires auditory evoked potentials or TMS, as well as fMRI and
diffusion tensor imaging for fiber tracts. Somatosensory cortex is most
effectively mapped by somatosensory evoked potentials. Crucial eloquent areas,
such as the central sulcus, primary somatomotor areas, corticospinal tract must
be defined and for some areas that must be removed, potential compensations may
be identified. Oncological/functional ratio must be optimized, resecting the
tumor maximally but also sparingly, as far as possible, the areas that mediate
indispensable functions. In some cases, a transient postoperative deficit may be
inevitable. In this article, we review intraoperative exploration of motricity,
language, somatosensory, visual and vestibular function, calculation, memory and
components of consciousness.
PMID- 28506487
TI - A review of monopolar motor mapping and a comprehensive guide to continuous
dynamic motor mapping for resection of motor eloquent brain tumors.
AB - Monopolar mapping of motor function differs from the most commonly used method of
intraoperative mapping, i.e. bipolar direct electrical stimulation at 50-60Hz
(Penfield technique mapping). Most importantly, the monopolar probe emits a
radial, homogenous electrical field different to the more focused inter-tip
bipolar electrical field. Most users combine monopolar stimulation with the short
train technique, also called high frequency stimulation, or train-of-five
techniques. It consists of trains of four to nine monopolar rectangular
electrical pulses of 200-500MUs pulse length with an inter stimulus interval of 2
4msec. High frequency short train stimulation triggers a time-locked motor-evoked
potential response, which has a defined latency and an easily quantifiable
amplitude. In this way, motor thresholds might be used to evaluate a current-to
distance relation. The homogeneous electrical field and the current-to-distance
approximation provide the surgeon with an estimate of the remaining distance to
the corticospinal tract, enabling the surgeon to adjust the speed of resection as
the corticospinal tract is approached. Furthermore, this stimulation paradigm is
associated with a lower incidence of intraoperative seizures, allowing continuous
stimulation. Hence, monopolar mapping is increasingly used as part of a strategy
of continuous dynamic mapping: ergonomically integrated into the surgeon's tools,
the monopolar probe reliably provides continuous/uninterrupted feedback on motor
function. As part of this strategy, motor mapping is not any longer a time
consuming interruption of resection but rather a radar-like, real-time
information system on the spatial relationship of the current resection site to
eloquent motor structures.
PMID- 28506488
TI - Perioperative functional neuroimaging of gliomas in eloquent brain areas.
AB - Surgical resection of gliomas involving eloquent brain areas must be maximal in
order to improve patients' survival, and safe to prevent postoperative
impairments. Therefore, the precise spatial relationship between the lesion and
eloquent brain areas needs to be established. Functional magnetic resonance
imaging and diffusion tensor imaging are robust methods with increasing
indications in neurosurgery for past decade. The aim of this review article is
not only to pinpoint the major limitations of these methods in order to avoid
erroneous conclusions, but also to detail practical aspects associated with the
main paradigms routinely used in functional magnetic resonance imaging, and to
discuss recent validation of functional magnetic resonance imaging and diffusion
tensor imaging results with direct electrical stimulation during awake surgery.
PMID- 28506489
TI - Enhancement of rotator cuff tendon-bone healing with fibroblast growth factor 2
impregnated in gelatin hydrogel sheets in a rabbit model.
AB - BACKGROUND: Application of fibroblast growth factor 2 (FGF-2) may improve the
healing response after rotator cuff (RC) surgical repair. This study aimed to
determine whether FGF-2-impregnated gelatin hydrogel sheet (GHS) incorporation
into the bony trough on the greater tuberosity facilitates healing after RC
surgical repair in rabbits. METHODS: We assigned 120 adult male Japanese white
rabbits treated with unilateral surgery for supraspinatus tendon repair into the
following groups: suture-only group (suture); suture and GHS with phosphate
buffered saline (carrier); suture and GHS with 3 ug of FGF-2 (F3); and suture and
GHS with 30 ug of FGF-2 (F30). The effect of FGF-2 was assessed using histologic,
biomechanical, and microcomputed tomography evaluations at 2, 6, and 12 weeks.
RESULTS: At 12 weeks, loose fibrovascular tissues emerged at the repair site in
the suture and carrier groups and dense tendon-like tissues in the F3 and F30
groups, which demonstrated significantly higher ultimate load-to-failure and
stress-to-failure at 12 weeks than that in the suture and carrier groups.
Microcomputed tomography imaging showed ectopic calcification formation in some
specimens from each group. Appearances or frequencies were similar among groups.
The histologic and biomechanical effects of FGF-2 on RC healing were obvious at
>=6 weeks postoperatively. CONCLUSION: FGF-2-impregnated GHS incorporation into
the bony trough on the greater tuberosity before RC surgical repair is feasible
and results in histologic and biomechanical improvements during RC healing in
rabbits. No detrimental effect on ectopic calcification was observed.
PMID- 28506490
TI - Early range of motion exercise in pediatric patients with olecranon fractures
treated with tension band suture with double loops and double knots.
AB - BACKGROUND: Pediatric patients with olecranon fractures are uncommon. The tension
band suture technique was introduced to reduce the burden of implant removal and
other complications. However, to our knowledge, early range of motion (ROM)
exercise has not been introduced in this population of patients. Double Vicryl
loops and knots with 2 cross-pins are used to maintain the benefits of the
tension band suture technique and to enhance fixation tensile strength. We
believe that early ROM exercises could be achieved without nonunion or fixation
failure. METHODS: Twelve pediatric patients with olecranon fractures were treated
with tension band suture with double loops and knots between 2004 and 2015.
Vicryl No. 1 was used for wiring. ROM exercises were initiated 1 week
postoperatively with a customized functional brace. Early functional outcomes
were evaluated by the Mayo Elbow Performance Score at every visit after 8 weeks
postoperatively. RESULTS: Nine boys and 3 girls (average age, 10.6 years; range,
5 years 7 months-16 years 2 months) were included in the study. Initial
displacement and angulation of the fractures were 5 mm (2-7 mm) and 12 degrees
(4 degrees -25 degrees ), respectively. Two cases had radial neck fractures of
the ipsilateral elbow. All patients had a perfect Mayo Elbow Performance Score
after 8 weeks postoperatively. Pin removals were performed at 13.1 weeks. No
complications, including growth arrest, were observed. DISCUSSION/CONCLUSION:
Tension band suture with double loops and knots, combined with early ROM
exercise, may be a complete alternative to tension band wiring.
PMID- 28506492
TI - Editorial.
PMID- 28506491
TI - Mapping of glenoid bone loss in recurrent anterior shoulder instability: is there
a particular deficit pattern?
AB - BACKGROUND: Glenoid bone loss in recurrent anterior shoulder instability is a
challenging problem for shoulder surgeons, and knowledge about the anatomy of
glenoid deficits is scarce. In this study, we tried to evaluate the pattern of
this pathology. METHODS: Our analysis included 44 shoulders from 44 patients with
recurrent anterior shoulder instability accompanied by a clinically relevant
glenoid bone loss. The defect size, the localization of the inferior defect edge,
and the defect angle were measured, and osseous landmarks were identified. An en
face view on 2-dimensional computed tomography scans of each patient was fitted
onto a template to create a deficit map for small (<23%) and large (>23%)
defects. RESULTS: The study cohort consisted of 9 women and 35 men with a mean
age of 33 +/- 11 years at the date of the scan. The defect size and localization
of the inferior defect edge showed significant differences between both groups,
indicating a more posterior position of larger defects. The defect angle,
however, showed no significant difference between small and large defects. Both
groups showed a vertical defect pattern. CONCLUSION: The osseous glenoid deficit
in recurrent anterior shoulder instability shows a vertical pattern with no
remarkable differences between small and large defects. This finding can
influence biomechanical models as well as surgical reconstruction.
PMID- 28506493
TI - Strategies for investigating the maternal-fetal interface in the first trimester
of pregnancy: What can we learn about pathology?
AB - The pathologies of the pregnancy complications pre-eclampsia (PE) and fetal
growth restriction (FGR) are established in the first trimester of human
pregnancy. In a normal pregnancy, decidual spiral arteries are transformed into
wide diameter, non-vasoactive vessels capable of meeting the increased demands of
the developing fetus for nutrients and oxygen. Disruption of this transformation
is associated with PE and FGR. Very little is known of how these first trimester
changes are regulated normally and even less is known about how they are
compromised in complicated pregnancies. Interactions between maternal and
placental cells are essential for pregnancy to progress and this review will
summarise the challenges in investigating this area. We will discuss how first
trimester studies of pregnancies with an increased risk of developing PE/FGR have
started to provide valuable information about pregnancy at this most dynamic and
crucial time. We will discuss where there is scope to progress these studies
further by refining the ability to identify compromised pregnancies at an early
stage, by integrating information from many cell types from the same pregnancy,
and by improving our methods for modelling the maternal-fetal interface in vitro.
PMID- 28506494
TI - Sociomics: Using Omic Approaches to Understand Social Evolution.
AB - All of life is social, from genes cooperating to form organisms, to animals
cooperating to form societies. Omic approaches offer exceptional opportunities to
solve major outstanding problems in the study of how sociality evolves. First,
omics can be used to clarify the extent and form of sociality in natural
populations. This is especially useful in species where it is difficult to study
social traits in natural populations, such as bacteria and other microbes.
Second, omics can be used to examine the consequences of sociality for genome
evolution and gene expression. This is especially useful in cases where there is
clear variation in the level of sociality, such as the social insects. Major
tasks for the future are to apply these approaches to a wider range of non-model
organisms, and to move from exploratory analyses to the testing of evolutionary
theory.
PMID- 28506495
TI - Relationship between patient group participation and self-care agency among
patients with a history of cardiac surgery: A cross-sectional study.
AB - BACKGROUND: Little is known regarding the influence of participation in patient
groups on self-care in patients with a cardiac surgery history. OBJECTIVES: To
investigate the relationship between patient group participation and self-care
among patients with a cardiac surgery history. METHODS: Participants were 956
patients with cardiac surgery history from a patient group. Information on self
care agency, patient group participation, and health status was collected through
a self-administered questionnaire. RESULTS: There were 566 valid responses.
Participants were mostly male (76.4%), and the mean age was 70.6 years. A high
social support level from a patient group was associated with each subscale of
the self-care agency as follows: self-care operations (odds ratio [OR] 1.08, 95%
confidence interval [CI] 1.04-1.12), adjusting one's condition (OR 1.04, 95% CI
1.01-1.07), and attention to self-care (OR 1.05, 95% CI 1.02-1.07). CONCLUSIONS:
Patient group participation may promote self-care performance in patients with a
cardiac surgery history.
PMID- 28506496
TI - Twins labeling-liquid chromatography/mass spectrometry based metabolomics for
absolute quantification of tryptophan and its key metabolites.
AB - Tryptophan metabolism plays a crucial role in mediating gastrointestinal
function. Here, in order to absolutely quantify tryptophan and its metabolites, a
liquid chromatography-mass spectrometry (LC-MS) based targeted metabolomics
approach was developed using N-dimethyl-/N-diethyl-amino naphthalene-1-sulfonyl
chloride (Dns/Dens-Cl) as twins labeling (TL) reagents. Dns-Cl is famous in amine
and phenol derivations, and structure is similar with Dens-Cl. The introduction
of easily protonated moiety of tertiary ammonium-containing part in the
derivatives from Dns to tryptophan and its metabolites not only improved the LC
separation but also enhanced their MS response. In addition, the Dens labeled
standards were used as internal standards to compensate for matrix effects and
ensure accurate quantifications. With the proposed method, twelve metabolites in
tryptophan pathway could be detected at sub-ng/mL levels using only 20MUL rat
serum (the limit of detection could reach 3pg/mL for tryptamine, N-acetyl
serotonin and 6-hydroxymelatonin). The sensitivity was enhanced about 1-2 orders
of magnitude compared with non-derivatization method. Focusing on tryptophan
pathway, the method was successfully applied to determine the absolute serum
concentrations of twelve tryptophan metabolites in a vincristine-induced ileus
rat model. A significant down-regulation of the tryptophan metabolism along the
kynurenine pathway and up-regulation of serotonin pathway were uncovered. Our
findings provide a deeper insight into the mechanism of gastrointestinal
dysfunction.
PMID- 28506497
TI - Comparison of enzymatic hydrolysis in a centrifugal partition chromatograph and
stirred tank reactor.
AB - Recently the Centrifugal Partition Chromatography (CPC) device is investigated as
a reactor for biocatalytic reactions, as it enables biocatalyst immobilization
without solid support and continuous operation of biphasic reaction systems.
However, a detailed determination of the enzymes behavior in the CPC reactor and
comparison to a classical stirred tank reactor (STR) for biphasic enzyme
catalysis is not shown yet. In this study, the performance of an enzymatic
biphasic hydrolysis reaction using lipase from Candida rugosa is systematically
evaluated using a STR. The results are compared to different experiments
conducted in the CPC reactor and used to evaluate the reaction performance in
each. The same characteristics and limitations were observed in STR and CPC. At
all states the CPC provided a similar reaction performance. However, the reaction
in the CPC runs faster into limitations and was not easily scalable due to
complex effects of the flow pattern. Although the enzyme was immobilized
successfully and the activity of the lipase was preserved during CPC operation
optimizations are needed to make the CPC reactor more competitive. For instance,
scaling up the chamber geometry seems to be mandatory to increase the reaction
performance, which may promote this reactor concept as an alternative to common
devices for continuous biphasic biocatalytic reactions.
PMID- 28506499
TI - Determination of butyltins, phenyltins and octyltins in foods with preservation
of their moieties: A critical review on analytical methods.
AB - Tributyltin and triphenyltin have been extensively applied in anti-fouling paints
since the 1960s. Hence, organotin compounds (OTCs), especially butyltins and
phenyltins, in seafood has been of concern for decades. Even though the
"International Convention on the Control of Harmful Anti-Fouling Systems on
Ships, 2001" entered into force internationally in 2008 and prohibited the use of
OTCs in anti-fouling paints used on ships, the analysis of OTCs in seafood was
not commonly included in routine monitoring programmes. Besides, species of
triphenyltin, including triphenyltin hydroxide and acetate, have been used as
pesticides and may accumulate in food. Moreover, the European Food Safety Agency
established a group tolerable daily intake for tributyltin, dibutyltin,
triphenyltin and dioctyltin in 2004 as they exert their immunotoxic effects by
similar mode of action and potency. Therefore, suitable methods are needed to
analyze butyl-, phenyl- and octyl-tins simultaneously in food without affecting
their moieties. This review aims to provide background information in this area.
PMID- 28506498
TI - Sweet spot matching: A thin-layer chromatography-based countercurrent solvent
system selection strategy.
AB - TLC-based strategies were proposed in 1979 (Hostettmann et al.) and 2005 (Friesen
& Pauli; GUESS method) to minimize the number of partitioning experiments
required for countercurrent separation (CCS) solvent system selection. As semi
empirical approaches, both proposed that the K values defining the sweet spot of
optimal CCS corresponded to a matching Rf value range from the silica gel TLC
plate developed in the organic phase of a biphasic or a corresponding monophasic
solvent system. Despite their simplicity, there has been an absence of
theoretical support and a deficiency of reported experimental evidence. The
present study explores the theory required to develop correlations between Rf and
K. All theoretical models surmise that the optimal Rf value range should be
centered at 0.5. In order to validate the feasibility of the concept of matching
Rf and K values, 43 natural products and six solvent system families were
investigated. Out of 62 correlations, 45 resulted in matched Rf and K values.
Based on this study, practical guidelines for the TLC-based prediction strategy
are provided. These approaches will equip CCS users with an updated understanding
of how to apply the TLC-based solvent system selection strategy to accelerate a
targeted selection of CCS conditions.
PMID- 28506501
TI - Sympathetic control of the brain circulation: Appreciating the complexities to
better understand the controversy.
AB - Although the human cerebral circulation is richly innervated with sympathetic
nerve fibers, the role of sympathetic nerve activity (SNA) on the regulation of
cerebral blood flow (CBF) remains debated. Several issues may be responsible for
the conflicting conclusions reported in the animal vs. human literature in
regards to the sympathetic control of the brain circulation. Furthermore, due to
the physiological consequences associated with SNA blockade (e.g. changes in
blood pressure and cardiac output), and differences in methodology (e.g.
assessment of CBF), interpretation of the role of SNA in CBF regulation in humans
is challenging. The goals of this brief review are to provide an overview of the
role of neural control in the regulation of CBF, with a focus on SNA and discuss
the likely reasons behind the controversial influence of SNA on CBF regulation. A
final objective of this article is to critically review the various methods
available to measure CBF and highlight their strengths and weaknesses to provide
insight in SNA regulation of CBF.
PMID- 28506500
TI - Autonomic and electrocardiographic findings in Parkinson's disease.
AB - Parkinson disease (PD) is a progressive neurodegenerative disorder characterized
by motor and non-motor symptoms and signs. Many reports suggest that diminished
heart rate variability occurs early, even prior to the cardinal signs of PD. In a
longitudinal study of PD, we evaluated whether heart rate variability (HRV)
obtained using a 10-second ECG tracing, and the electrocardiographic QT-interval
would be associated with PD severity and progression. Subjects were derived from
a longitudinal study of 1741 individuals with early, stable PD. The severity of
PD was measured using the global statistical test (GST). In a subset, the heart
rate corrected QT-interval (QTcB) was calculated for each electrocardiogram
(ECG). The HRV was measured for each ECG and then transformed to fit a normal
distribution. The baseline analysis included 653 subjects, with 256 completing
the 5-year follow up study. There was an association (P<0.05) between QTcB and PD
severity in individuals that were taking QT-interval affecting drugs. A longer QT
interval at baseline was associated with more advanced PD at 5years (P<0.05), and
greater disease progression over 5years (P<0.05). There was an association
between diminished HRV and an orthostatic decrease in standing blood pressure at
baseline in individuals with PD (P<0.05). HRV was not associated with PD severity
or progression. In conclusion, we were able to detect measurable associations
between the QTcB interval and PD severity, PD severity 5years later, and the
change in disease over time. However, routine ECG tracings appear inadequate for
the evaluation of autonomic function in PD.
PMID- 28506503
TI - Extended Clinical Spectrum of Anti-N-Methyl-d-Aspartate Receptor Encephalitis in
Children: A Case Series.
AB - OBJECTIVE: There is a wide spectrum of clinical manifestations in children with
anti-N-methyl-d-aspartate (NMDA) receptor antibody encephalitis from two
different health care settings. METHODS: We describe our experience with 13
patients (median age, 7 years; range, 5 months to 19 years) presenting to
tertiary referral centers in India and the United States. RESULTS: Initial
manifestations were neurological (seizures or movement disorders) in eight
patients, and psychiatric (e.g., emotional lability and hallucination) in five
patients. Symptoms during the clinical course included seizures in ten patients,
movement disorders (dyskinesia and choreiform movements) in 11 patients, and
behavioral changes (aggressiveness and insomnia) in ten patients. Concomitant
infections (herpes simplex virus 1, tuberculous meningitis, and influenza A) were
present in three patients. Analysis of the cerebrospinal fluid in all except two
cases preceded by infection (herpes simplex virus encephalitis and tuberculous
meningitis) was unremarkable. Treatment included intravenous
immunoglobulin/methylprednisolone (11 patients), rituximab (eight patients),
plasmapheresis (two patients), and cyclophosphamide (two patients). Six patients
recovered completely. Two patients had mild residual neurological deficits,
whereas four had severe residual neurological deficits. Two patients had profound
autonomic instability, which was the cause of death for one of them. Two patients
relapsed at two and six months after the initial recovery. CONCLUSIONS: We
describe the differences and similarities of clinical presentation, test results,
and response to treatment of children with anti-N-methyl-d-aspartate receptor
encephalitis from India and the United States. Included is a description of one
of the youngest patients with anti-N-methyl-d-aspartate receptor encephalitis
(five months) and the first patient to be reported in association with
tuberculous meningitis.
PMID- 28506504
TI - Anti-N-Methyl-d-Aspartate Receptor Encephalitis Appearing as a New-Onset
Psychosis: Disease Course in Children and Adolescents Within the California
Encephalitis Project.
AB - BACKGROUND: Given that psychiatric symptoms are common, not only during the
course of the illness but also on presentation, in children and adolescents with
anti-N-methyl-d-aspartate receptor encephalitis, it is important that
practitioners possess an adequate understanding of the clinical features and
potential treatment of this disease. We describe the clinical characteristics of
24 patients who presented to the California Encephalitis Project. METHODS:
Patients were referred by physicians, and standardized forms were used to gather
demographic, clinical, and laboratory data. RESULTS: Twenty-four patients between
ages two and 18 years were identified. Psychosis was a primary presenting symptom
in two thirds of patients, and just over 20% of these were admitted to an
inpatient psychiatric facility. Ultimately, all patients developed psychiatric
symptoms during the course of the illness. There was a characteristic progression
of symptoms that was consistent with that noted in other studies, with prominent
psychiatric symptoms initially, which then progressed to seizures and autonomic
instability in most patients. All of those examined developed movement
abnormalities, which included primarily orofacial dyskinesias and choreiform
movements. CONCLUSIONS: Anti-N-methyl-d-aspartate receptor encephalitis, unlike
other paraneoplastic or autoimmune encephalitides, affects those 18 years and
under an estimated 40% of the time based on prior studies. Recognizing the signs
and symptoms of this condition is essential to making a diagnosis and initiating
timely treatment. Child psychiatrists have an important role in this disorder.
PMID- 28506505
TI - The Utility of Surveillance Electroencephalography to Guide Early Antiepileptic
Drug Therapy in Infants With Tuberous Sclerosis Complex.
AB - BACKGROUND: Seizures are a common early presentation in infants with tuberous
sclerosis complex (TSC) and can be preceded by electrographic changes on
electroencephalography (EEG) before clinical seizure onset. A limited number of
studies have addressed the initial EEG findings in TSC and the outcome of early
treatment with antiepileptic medication prior to clinical seizure onset. METHODS:
We describe two infants with tuberous sclerosis complex whose surveillance EEG
showed focal seizures that were not previously recognized by caregivers. We
review previously reported patients with TSC with early EEG findings. Our
patients were started on vigabatrin after the onset of focal seizures with the
aim of preventing seizure recurrence, halting the possible progression to
infantile spasms or focal seizures, and preventing neurodevelopmental decline.
RESULTS: Both patients remain seizure free and have reached appropriate
developmental milestones. CONCLUSIONS: We recommend early serial EEG monitoring
once a diagnosis of TSC is suspected or confirmed in infants. Additional
prospective studies are needed to assess the long-term outcome of early
antiepileptic drug initiation as soon as electrographic seizure activity is
detected.
PMID- 28506502
TI - Autonomic dysreflexia after spinal cord injury: Systemic pathophysiology and
methods of management.
AB - Traumatic spinal cord injury (SCI) has widespread physiological effects beyond
the disruption of sensory and motor function, notably the loss of normal
autonomic and cardiovascular control. Injury at or above the sixth thoracic
spinal cord segment segregates critical spinal sympathetic neurons from
supraspinal modulation which can result in a syndrome known as autonomic
dysreflexia (AD). AD is defined as episodic hypertension and concomitant
baroreflex-mediated bradycardia initiated by unmodulated sympathetic reflexes in
the decentralized cord. This condition is often triggered by noxious yet
unperceived visceral or somatic stimuli below the injury level and if severe
enough can require immediate medical attention. Herein, we review the
pathophysiological mechanisms germane to the development of AD, including
maladaptive plasticity of neural circuits mediating abnormal sympathetic reflexes
and hypersensitization of peripheral vasculature that collectively contribute to
abnormal hemodynamics after SCI. Further, we discuss the systemic effects of
recurrent AD and pharmacological treatments used to manage such episodes.
Contemporary research avenues are then presented to better understand the
relative contributions of underlying mechanisms and to elucidate the effects of
recurring AD on cardiovascular and immune functions for developing more targeted
and effective treatments to attenuate the development of this insidious syndrome
following high-level SCI.
PMID- 28506506
TI - Endovascular rewarming in the emergency department for moderate to severe
accidental hypothermia.
AB - BACKGROUND: Endovascular temperature control catheters can be utilized for
emergent rewarming in accidental hypothermia. The purpose of this study was to
compare patients with moderate to severe hypothermia rewarmed with an
endovascular temperature control catheter versus usual care at our institution.
METHODS: We conducted a retrospective, observational cohort study of patients
with moderate to severe accidental hypothermia (core body temperature less than
32 degrees C) in the Emergency Department of an urban, tertiary care medical
center. We identified the rewarming techniques utilized for each patient,
including those who had an endovascular temperature control catheter placed
(Quattro(c) or Icy(c) catheter, CoolGuard(c) 3000 regulation system, Zoll
Medical). Rewarming rates and outcomes were compared for patients with and
without the endovascular temperature control catheter. We systematically screened
for procedural complications. RESULTS: There were 106 patients identified with an
initial core temperature less than or equal to 32 degrees C; 52 (49%) patients
rewarmed with an endovascular temperature control catheter. Other methods of
rewarming included external forced-air rewarming (85, 80%), bladder lavage (17,
16%), gastric lavage (10, 9%), closed pleural lavage (6, 6%), and peritoneal
lavage (3, 3%). Rate of rewarming did not differ between the groups with and
without catheter-based rewarming (1.3 degrees C/h versus 1.0 degrees C/h,
difference 0.3 degrees C, 95% confidence interval [CI] of the difference 0-0.6
degrees C) and neither did survival (70% versus 71%, difference 1%, 95% CI -17 to
20%). We did not identify any significant vascular injuries resulting from
endovascular catheter use. CONCLUSION: The endovascular temperature control
system was not associated with an increased rate of rewarming in this cohort with
moderate to severe hypothermia; however, this technique appears to be safe and
feasible.
PMID- 28506507
TI - Syndrome surveillance of fentanyl-laced heroin outbreaks: Utilization of EMS,
Medical Examiner and Poison Center databases.
AB - OBJECTIVE: Describe surveillance data from three existing surveillance systems
during an unexpected fentanyl outbreak in a large metropolitan area. METHODS: We
performed a retrospective analysis of three data sets: Chicago Fire Department
EMS, Cook County Medical Examiner, and Illinois Poison Center. Each included data
from January 1, 2015 through December 31, 2015. EMS data included all EMS
responses in Chicago, Illinois, for suspected opioid overdose in which naloxone
was administered and EMS personnel documented other criteria indicative of opioid
overdose. Medical Examiner data included all deaths in Cook County, Illinois,
related to heroin, fentanyl or both. Illinois Poison Center data included all
calls in Chicago, Illinois, related to fentanyl, heroin, and other prescription
opioids. Descriptive statistics using Microsoft Excel(r) were used to analyze the
data and create figures. RESULTS: We identified a spike in opioid-related EMS
responses during an 11-day period from September 30-October 10, 2015. Medical
Examiner data showed an increase in both fentanyl and mixed fentanyl/heroin
related deaths during the months of September and October, 2015 (375% and 550%
above the median, respectively.) Illinois Poison Center data showed no
significant increase in heroin, fentanyl, or other opioid-related calls during
September and October 2015. CONCLUSION: Our data suggests that EMS data is an
effective real-time surveillance mechanism for changes in the rate of opioid
overdoses. Medical Examiner's data was found to be valuable for confirmation of
EMS surveillance data and identification of specific intoxicants. Poison Center
data did not correlate with EMS or Medical Examiner data.
PMID- 28506508
TI - The influence of substance misuse on clinical outcomes following burn.
AB - INTRODUCTION: Ongoing increases in the prevalence of substance misuse among burn
injured patients necessitate a contemporary analysis of the association between
substance misuse and clinical outcomes in burn-injured adults. METHODS: We
conducted a retrospective cohort study of 1199 patients admitted to a regional
burn center. History of substance misuse was derived from a prospective clinical
registry and categorized as alcohol, illicit drug, or both. The primary outcome
was hospital length of stay; association of substance misuse and inpatient
complications were secondary outcomes. Multivariable logistic regression was used
to model the association between categories of substance misuse and each outcome,
adjusting for patient and injury characteristics. RESULTS: The incidence of
substance misuse was 34% overall. After adjustment for patient and injury
characteristics, drug misuse was associated with a significantly longer length of
stay (RR 1.12; 95% CI 1.00-1.25), as was alcohol misuse (RR 1.32; 95% CI 1.14
1.52), and drug/alcohol misuse (RR 1.34; 95% CI 1.16-1.56). Drug/alcohol misuse
was associated with significantly higher rates of bacteremia (OR 3.84; 95% CI
1.83-8.04) and sepsis (OR 2.50; CI 1.13-5.53). CONCLUSIONS: A history of
substance misuse is associated with an increased risk of inpatient complications
and longer hospital stay. Providers should be cognizant of increased
complications in this cohort with a view to improving outcomes.
PMID- 28506509
TI - Sub fascial flap based on the supraclavicular artery in reconstruction of neck
burn contractures.
AB - This study presents 3 cases of women ages ranged from 25 to 52 years with
anterior cervical contractures caused by burns that resulted in functional and
aesthetic deficit. Contracture release in 3 patients and reconstruction was done
using a sub-fascial flap whose main pedicle was the supraclavicular artery and
the occipito-postero-cervical vessels that were preserved. The flap was designed
differently from the classically described that uses the skin of the shoulder but
which presents differences of color and texture with relation to the skin of the
neck. The results were satisfactory and no complications such as infections or
necrosis.
PMID- 28506510
TI - Can Occult Invasive Disease in Ductal Carcinoma In Situ Be Predicted Using
Computer-extracted Mammographic Features?
AB - RATIONALE AND OBJECTIVES: This study aimed to determine whether mammographic
features assessed by radiologists and using computer algorithms are prognostic of
occult invasive disease for patients showing ductal carcinoma in situ (DCIS) only
in core biopsy. MATERIALS AND METHODS: In this retrospective study, we analyzed
data from 99 subjects with DCIS (74 pure DCIS, 25 DCIS with occult invasion). We
developed a computer-vision algorithm capable of extracting 113 features from
magnification views in mammograms and combining these features to predict whether
a DCIS case will be upstaged to invasive cancer at the time of definitive
surgery. In comparison, we also built predictive models based on physician
interpreted features, which included histologic features extracted from biopsy
reports and Breast Imaging Reporting and Data System-related mammographic
features assessed by two radiologists. The generalization performance was
assessed using leave-one-out cross validation with the receiver operating
characteristic curve analysis. RESULTS: Using the computer-extracted mammographic
features, the multivariate classifier was able to distinguish DCIS with occult
invasion from pure DCIS, with an area under the curve for receiver operating
characteristic equal to 0.70 (95% confidence interval: 0.59-0.81). The physician
interpreted features including histologic features and Breast Imaging Reporting
and Data System-related mammographic features assessed by two radiologists showed
mixed results, and only one radiologist's subjective assessment was predictive,
with an area under the curve for receiver operating characteristic equal to 0.68
(95% confidence interval: 0.57-0.81). CONCLUSIONS: Predicting upstaging for DCIS
based upon mammograms is challenging, and there exists significant interobserver
variability among radiologists. However, the proposed computer-extracted
mammographic features are promising for the prediction of occult invasion in
DCIS.
PMID- 28506511
TI - An Abbreviated Protocol for High-risk Screening Breast Magnetic Resonance
Imaging: Impact on Performance Metrics and BI-RADS Assessment.
AB - RATIONALE AND OBJECTIVES: Annual breast magnetic resonance imaging (MRI) is
recommended to screen high-risk populations for breast cancer, although costs are
significant. This study assesses the performance of an abbreviated MRI protocol
as a resource-efficient approach for screening patients at high-risk of breast
cancer, and assesses whether the abbreviated protocol alters the assigned Breast
Imaging Reporting and Data System (BI-RADS) category. MATERIALS AND METHODS: This
is a prospective paired cohort study performed in an academic ambulatory setting.
MRI images of women at high risk of breast cancer were reviewed using an
abbreviated MRI protocol, followed by an immediate review of additional sequences
included in a full diagnostic protocol. BI-RADS assessments, including all
changes and interpretation times, were recorded for both the abbreviated and full
protocol reviews. Cancer detection rate, positive predictive value 3 (PPV3),
sensitivity, and specificity were calculated. RESULTS: A total of 1052 MRI cases
were reviewed. The cancer detection rate was 13.3 per 1000 with a PPV3 of 30.4%
based on the full protocol. Review of sequences included in the full protocol
resulted in a change in the final BI-RADS assessments in 3.4% of the cases, the
majority of which did not change clinical management with respect to biopsy. The
sensitivity and specificity of the abbreviated and full protocols were not
significantly different. CONCLUSIONS: This pilot study of an abbreviated MRI
protocol demonstrates effective performance in cancer detection. BI-RADS
assessments were rarely altered with the additional information afforded by the
full protocol. The abbreviated protocol holds promise for resource-efficient
breast cancer screening in high-risk women.
PMID- 28506512
TI - Clinical Workflow Can Threaten Resident Education.
PMID- 28506513
TI - Letter to the Editor: Use of Publicly Available Image Resources.
PMID- 28506514
TI - A Novel Cooling Method and Comparison of Active Rewarming of Mildly Hypothermic
Subjects.
AB - OBJECTIVE: To compare the effectiveness of arteriovenous anastomosis (AVA) vs
heated intravenous fluid (IVF) rewarming in hypothermic subjects. Additionally,
we sought to develop a novel method of hypothermia induction. METHODS: Eight
subjects underwent 3 cooling trials each to a core temperature of 34.8+/-0.6
(32.7 to 36.3 degrees C [mean+/-SD with range]) by 14 degrees C water immersion
for 30 minutes, followed by walking on a treadmill for 5 minutes. Core
temperatures (Deltates) and rates of cooling ( degrees C/h) were measured.
Participants were then rewarmed by 1) control: shivering only in a sleeping bag;
2) IVF: shivering in sleeping bag and infusion of 2 L normal saline warmed to 42
degrees C at 77 mL/min; and 3) AVA: shivering in sleeping bag and circulation of
45 degrees C warmed fluid through neoprene pads affixed to the palms and soles of
the feet. RESULTS: Cold water immersion resulted in a decrease of 0.5+/-0.5
degrees C Deltates and 1+/-0.3 degrees C with exercise (P < .01); with an
immersion cooling rate of 0.9+/-0.8 degrees C/h vs 12.6+/-3.2 degrees C/h with
exercise (P < .001). Temperature nadir reached 35.0+/-0.5 degrees C. There were
no significant differences in rewarming rates between the 3 conditions
(shivering: 1.3+/-0.7 degrees C/h, R2 = 0.683; IVF 1.3+/-0.7 degrees C/h, R2 =
0.863; and AVA 1.4+/-0.6 degrees C/h, R2 = 0.853; P = .58). Shivering inhibition
was greater with AVA but was not significantly different (P = .07). CONCLUSIONS:
This study developed a novel and efficient model of hypothermia induction through
exercise-induced convective afterdrop. Although there was not a clear benefit in
either of the 2 active rewarming methods, AVA rewarming showed a nonsignificant
trend toward greater shivering inhibition, which may be optimized by an improved
interface.
PMID- 28506515
TI - Combined semi-empirical screening and design of experiments (DOE) approach to
identify candidate formulations of a lyophilized live attenuated tetravalent
viral vaccine candidate.
AB - A combination experimental approach, utilizing semi-empirical excipient screening
followed by statistical modeling using design of experiments (DOE), was
undertaken to identify stabilizing candidate formulations for a lyophilized live
attenuated Flavivirus vaccine candidate. Various potential pharmaceutical
compounds used in either marketed or investigative live attenuated viral vaccine
formulations were first identified. The ability of additives from different
categories of excipients, either alone or in combination, were then evaluated for
their ability to stabilize virus against freeze-thaw, freeze-drying, and
accelerated storage (25 degrees C) stresses by measuring infectious virus titer.
An exploratory data analysis and predictive DOE modeling approach was
subsequently undertaken to gain a better understanding of the interplay between
the key excipients and stability of virus as well as to determine which
combinations were interacting to improve virus stability. The lead excipient
combinations were identified and tested for stabilizing effects using a
tetravalent mixture of viruses in accelerated and real time (2-8 degrees C)
stability studies. This work demonstrates the utility of combining semi-empirical
excipient screening and DOE experimental design strategies in the formulation
development of lyophilized live attenuated viral vaccine candidates.
PMID- 28506516
TI - Waning protection following 5 doses of a 3-component diphtheria, tetanus, and
acellular pertussis vaccine.
AB - BACKGROUND: The effectiveness of diphtheria, tetanus, and acellular pertussis
(DTaP) vaccines wanes substantially after the 5th dose given at ages 4-6years,
but has not been described following 5 doses of the same type of DTaP vaccine. We
investigated waning effectiveness against pertussis in California over nearly
10years, which included large pertussis outbreaks, following 5 doses of GSK DTaP
vaccines (DTaP3). METHODS: We conducted a case-control study (NCT02447978) of
children who received 5 doses of DTaP at Kaiser Permanente Northern California
from 01/2006 through 03/2015. We compared time since the 5th dose in confirmed
pertussis polymerase chain reaction (PCR)-positive cases with pertussis PCR
negative controls. We used logistic regression adjusted for calendar time, age,
sex, race, and service area to estimate the effect of time since the 5th DTaP
dose on the odds of pertussis. Our primary analysis evaluated waning after 5
doses of DTaP3. We also examined waning after 5 doses of any type of DTaP
vaccines. RESULTS: Our primary analysis compared 340 pertussis cases diagnosed at
ages 4-12years with 3841 controls. The any DTaP analysis compared 462 pertussis
cases with 5649 controls. The majority of all DTaP doses in the study population
were DTaP3 (86.8%). Children who were more remote from their 5th dose were less
protected than were children whose 5th dose was more recent; the adjusted odds of
pertussis increased by 1.27 per year (95% CI 1.10, 1.46) after 5 doses of DTaP3
and by 1.30 per year (95% CI 1.15, 1.46) after any 5 DTaP vaccines doses.
CONCLUSIONS: Waning protection after DTaP3 was similar to that following 5 doses
of any type of DTaP vaccines. This finding is not unexpected as most of the DTaP
vaccines administered were DTaP3. Following 5 doses of DTaP3 vaccines, protection
from pertussis waned 27% per year on average. NCT number: NCT02447978.
PMID- 28506517
TI - Fish oil supplementation benefits the murine host during the acute phase of a
parasitic infection from Trypanosoma cruzi.
AB - Long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) are known to
modulate a variety of immune cell functions. On occasion, this has led to
diminished host resistance to certain viral and bacterial infections. Little is
known about the impact of n-3 PUFA on host resistance to parasitic infection,
however, based on results from a small study conducted more than two decades ago,
we hypothesized that providing mice LC n-3 PUFA will diminish host resistance to
Trypanosoma cruzi, the parasitic pathogen responsible for Chagas disease. To
investigate this, C57BL/6 mice were supplemented by gavage (0.6% v/w) with
phosphate-buffered saline, corn oil (CO), or menhaden fish oil (FO, a fat source
rich in LC n-3 PUFA) for 15 days prior to T cruzi (Y strain) challenge and
throughout the acute phase of infection. FO supplementation was associated with a
transient 2-fold greater peak of blood parasitemia at 7 days postinfection (dpi),
whereas subsequent cardiac parasitemia was ~60% lower at 12 dpi. FO treatment
also ameliorated the leukopenia and thrombocytopenia observed in the early stages
of a T cruzi infection. FO supplementation reduced circulating and cardiac nitric
oxide at 7 and 12 dpi, respectively. FO supplementation altered ex vivo
prostaglandin E2 and cytokine and chemokine production by splenocytes isolated
from uninfected and infected mice. Overall, our results suggest that oral
administration of LC n-3 PUFA from FO can have beneficial effects on the host in
the early course of a T cruzi infection.
PMID- 28506518
TI - The addition of peanuts to habitual diets is associated with lower consumption of
savory non-core snacks by men and sweet non-core snacks by women.
AB - Snacking is associated with intakes of non-core foods which may predispose to
obesity. Peanuts have potential satiety benefits and may assist with weight
management; we hypothesized that peanut consumption would reduce intake of non
core snack foods due to compensation. We investigated the effects of adding
peanuts to a habitual diet on snacking habits and energy intake. Sixty-one
healthy participants (65+/-7years, body mass index 31+/-4kg/m2) consumed their
habitual diet with or without peanuts (56g/d for 32 women, 84g/d for 29 men) for
12weeks each in a randomized crossover design. Food diaries were analyzed at
baseline and after each 12-week period for meal and snack content and timing.
Total energy intake was higher (17% for men [P<.001], 9% for women [P<.001])
during the peanut phase. Body weight was 0.5+/-0.2kg (P=.010) greater during the
peanut phase. Snacking occasions increased during the peanut phase (53% for men
[P=.001], 14% for women [P=.01]). Servings of other snack foods did not change
during the peanut phase (P=.6) compared with control. However, sex-specific
analysis revealed that men and women consumed less savory (P<.001) and sweet
(P=.01) non-core snacks, respectively, during the peanut phase. Despite increased
energy intake and snacking frequency, peanuts may improve the diet through sex
specific reductions of non-core foods; for optimal energy balance, peanuts should
be substituted rather than added to the diet.
PMID- 28506519
TI - Sodium-Glucose Co-transporters and Their Inhibition: Clinical Physiology.
AB - Sodium-glucose cotransporter-2 (SGLT2) is selectively expressed in the human
kidney, where it executes reabsorption of filtered glucose with a high capacity;
it may be overactive in patients with diabetes, especially in the early,
hyperfiltering stage of the disease. As a therapeutic target, SGLT2 has been
successfully engaged by orally active, selective agents. Initially developed as
antihyperglycemic drugs, SGLT2 inhibitors have deployed a range of in vivo
actions. Consequences of their primary effect, i.e., profuse glycosuria and
natriuresis, involve hemodynamic (plasma volume and blood pressure reduction) and
metabolic pathways (increase in lipid oxidation and ketogenesis at the expense of
carbohydrate utilization); the hormonal mediation extends to insulin, glucagon,
and gastrointestinal peptides. Their initial trial in high-risk patients with
diabetes has provided evidence for marked reduction of cardiovascular risk. This
review focuses on the quantitative pharmacology of SGLT2 inhibitors, which can be
exploited to discover new physiology, in the heart, kidney, and brain.
PMID- 28506520
TI - The Evolving Role of Proton Beam Therapy for Sarcomas.
AB - As an alternative to conventional photon-based radiotherapy, radiation with
protons is recognised to offer considerable advantages. Today, central nervous
system tumours, various sarcomatous tumours, childhood cancer and head and neck
tumours are commonly treated with proton therapy. This review evaluates current
data from clinical and dosimetric trials on the treatment of selected sarcomatous
tumours like rhabdomyosarcoma, osteosarcoma, chordoma, chondrosarcoma and Ewing
sarcoma. Special considerations for paediatric tumours and future prospects of
proton therapy are outlined. Proton therapy is already an internal part in the
multidisciplinary management of childhood sarcomas in contiguity to sensitive
structures, especially at the base of skull, spine and pelvis. It offers special
advantages for tumours requiring high-precision radiotherapy, particularly when
total resection seems not feasible. Previous and ongoing research is generating
evidence for the benefit of protons in sarcoma patients. Up to now, proton
therapy has been safely applied with encouraging results. For future research,
prospective, multi-institutional, large registries are required to answer open
questions. Modern radiotherapy techniques, such as pencil beam scanning and
intensity modulation are increasingly established in proton therapy. More
research is needed to understand protons' limitations and potential.
PMID- 28506521
TI - Role of Imaging in Response Assessment and Individualised Treatment for Sarcomas.
AB - The first systematic response evaluation criteria were established by WHO, based
on the tumor size changes shortly after the computed tomography (CT) technique
became available to the daily practice. RECIST, a simplified version of WHO
criteria, and its newer version, RECIST1.1 are the currently available
international response evaluation criteria in solid tumors and remains based on
tumor size changes. While the introduction of molecularly targeted drugs has
significantly improved the survival in patient with sarcomas, the evaluation of
tumor response has become more complicated. Increasing number of studies have
reported the lack of shrinkage in responding tumors and raised concerns of
significant underestimation of responses using RECIST. The first such observation
was made on gastrointestinal stromal tumor (GIST) treated with imatinib. In GISTs
responding to imatinib, the degree of contrast enhancement on CT typically
decreases significantly compared with the baseline, and, regardless of whether
tumors shrink, heterogeneous hyperattenuating tumors become homogeneous
hypoattenuating tumors with a smaller enhancing solid component. In current
oncology practice, CT is a widely accepted method of evaluating tumor response.
CT images are relatively simple to acquire and can be reasonably reproduced with
no significant technical obstacles. FDG-PET is highly sensitive and specific in
identifying responding sarcomas. It has mostly been used as a problem solver and
for those with marginally resectable GIST. More recently, the utility of whole
body MRI is undergoing exploration. This article discusses the traditional size
based response evaluation criteria, and introduces new evidence based response
evaluation based on changes in morphology in addition to changes in tumor size on
CT images, and whole body imaging is introduced at the end.
PMID- 28506522
TI - Thick tumor capsule is a valuable risk factor for distant metastasis in
follicular thyroid carcinoma.
AB - OBJECTIVE: While the biological behavior of follicular thyroid carcinoma (FTC)
has been studied in great detail using clinical experience, few studies have
investigated pre- or intraoperative factors related to the risk of distant
metastasis (DM) among patients with FTC. The aim of this study was to analyze the
characteristics of FTC with DM. METHODS: This study retrospectively investigated
102 patients with FTC who underwent surgery between 1988 and 2013. We compared
clinicopathological characteristics between FTC with and without DM. RESULTS:
Univariate analysis revealed nodal metastasis (p=0.045), serum thyroglobulin (Tg)
at initial operation (>=1000ng/ml; p<0.0001), widely invasive appearance
according to macroscopic findings (p<0.0001), thick tumor capsule (>=1mm;
p<0.0001), vascular invasion (p=0.0003), extrathyroidal invasion (p=0.047), and
venous tumor embolism (p=0.045) as significant risk factors for DM. Multivariate
analysis conducted using pre- and intraoperative factors identified thick tumor
capsule (>=1mm), serum Tg at initial operation (>=1000ng/ml), and macroscopically
widely invasive appearance as risk factors independently associated with
development of DM. CONCLUSION: Patients with these risk factors should undergo
total thyroidectomy and radioactive iodine ablation.
PMID- 28506523
TI - Integration of population census and water point mapping data-A case study of
Cambodia, Liberia and Tanzania.
AB - Sustainable Development Goal (SDG) 6 has expanded the Millennium Development
Goals' focus from improved drinking-water to safely managed water services. This
expanded focus to include issues such as water quality requires richer monitoring
data and potentially integration of datasets from different sources. Relevant
data sets include water point mapping (WPM), the survey of boreholes, wells and
other water points, census and household survey data. This study examined
inconsistencies between population census and WPM datasets for Cambodia, Liberia
and Tanzania, and identified potential barriers to integrating the two datasets
to meet monitoring needs. Literatures on numbers of people served per water point
were used to convert WPM data to population served by water source type per area
and compared with census reports. For Cambodia and Tanzania, discrepancies with
census data suggested incomplete WPM coverage. In Liberia, where the data sets
were consistent, WPM-derived data on functionality, quantity and quality of
drinking water were further combined with census area statistics to generate an
enhanced drinking-water access measure for protected wells and springs. The
process revealed barriers to integrating census and WPM data, including exclusion
of water points not used for drinking by households, matching of census and WPM
source types; temporal mismatches between data sources; data quality issues such
as missing or implausible data values, and underlying assumptions about
population served by different water point technologies. However, integration of
these two data sets could be used to identify and rectify gaps in WPM coverage.
If WPM databases become more complete and the above barriers are addressed, it
could also be used to develop more realistic measures of household drinking-water
access for monitoring.
PMID- 28506524
TI - Contemporary Incidence and Cancer Control Outcomes of Primary Neuroendocrine
Prostate Cancer: A SEER Database Analysis.
AB - INTRODUCTION: Neuroendocrine carcinoma of the prostate (NEPC) is a rare entity.
We aimed at providing contemporary data on incidence and survival figures of de
novo NEPC. MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End
Results (SEER) database, we identified 309 individuals with de-novo NEPC
diagnosed between 2004 and 2013. We evaluated age-adjusted incidence rates over
the study. Kaplan-Meier analyses assessed overall survival (OS) after
stratification according to histologic subtype, metastatic status, and treatment.
Cox regression analyses tested the predictors of overall mortality, after
adjusting for confounders. RESULTS: A total of 309 cases of NEPC were identified
from 510,913 cases of prostate cancer. Metastatic disease was identified in 198
(64.1%) cases. The most common histologic subtype (n = 186; 60.2%) was small-cell
carcinoma (SCC). The age-adjusted incidence of NEPC significantly increased over
the study span. However, this increase only affected SCC (from 0.13/1,000,000
person-years in 2004 to 0.30/1,000,000 person-years in 2013; P = .001). Median
survival for NEPC was 10 months. After stratification by metastatic status, no
difference was observed according to SCC versus non-SCC. Treatment with radical
prostatectomy improved OS only among individuals with non-metastatic disease,
whereas radiation therapy did not affect OS rates. In multivariable Cox
regression analyses predicting overall mortality, metastatic stage (hazard ratio,
1.52; 95% confidence interval, 1.12-2.06; P < .01) and radical prostatectomy
(hazard ratio, 0.38; 95% confidence interval, 0.20-0.74; P < .01) achieved
independent predictor status. CONCLUSION: De-novo NEPC is extremely rare and will
be encountered in clinical practice by few urologists. Most cases are metastatic
at diagnosis. Prognosis is poor regardless of histologic type, especially in
metastatic stage.
PMID- 28506526
TI - Molecular Simulation and Biochemical Studies Support an Elevator-type Transport
Mechanism in EIIC.
AB - Enzyme IIC (EIIC) is a membrane-embedded sugar transport protein that is part of
the phosphoenolpyruvate-dependent phosphotransferases. Crystal structures of two
members of the glucose EIIC superfamily, bcChbC in the inward-facing conformation
and bcMalT in the outward-facing conformation, were previously solved. Comparing
the two structures led us to the hypothesis that sugar translocation could be
achieved by an elevator-type transport mechanism in which a transport domain
binds to the substrate and, through rigid body motions, transports it across the
membrane. To test this hypothesis and to obtain more accurate descriptions of
alternate conformations of the two proteins, we first performed collective
variable-based steered molecular dynamics (CVSMD) simulations starting with the
two crystal structures embedded in model lipid bilayers, and steered their
transport domain toward their own alternative conformation. Our simulations show
that large rigid-body motions of the transport domain (55 degrees in rotation
and 8 A in translation) lead to access of the substrate binding site to the
alternate side of the membrane. H-bonding interactions between the sugar and the
protein are intact, although the side chains of the binding-site residues were
not restrained in the simulation. Pairs of residues in bcMalT that are far apart
in the crystal structure become close to each other in the simulated model. Some
of these pairs can be cross-linked by a mercury ion when mutated to cysteines,
providing further support for the CVSMD-generated model. In addition, bcMalT
binds to maltose with similar affinities before and after the cross-linking,
suggesting that the binding site is preserved after the conformational change. In
combination, these results support an elevator-type transport mechanism in EIIC.
PMID- 28506525
TI - How Does Mg2+ Modulate the RNA Folding Mechanism: A Case Study of the G:C W:W
Trans Basepair.
AB - Reverse Watson-Crick G:C basepairs (G:C W:W Trans) occur frequently in different
functional RNAs. This is one of the few basepairs whose gas-phase-optimized
isolated geometry is inconsistent with the corresponding experimental geometry.
Several earlier studies indicate that through post-transcriptional modification,
direct protonation, or coordination with Mg2+, accumulation of positive charge
near N7 of guanine can stabilize the experimental geometry. Interestingly, recent
studies reveal significant variation in the position of putatively bound Mg2+.
This, in conjunction with recently raised doubts regarding some of the Mg2+
assignments near the imino nitrogen of guanine, is suggestive of the existence of
multiple Mg2+ binding modes for this basepair. Our detailed investigation of Mg2+
bound G:C W:W Trans pairs occurring in high-resolution RNA crystal structures
shows that they are found in 14 different contexts, eight of which display Mg2+
binding at the Hoogsteen edge of guanine. Further examination of occurrences in
these eight contexts led to the characterization of three different Mg2+ binding
modes: 1) direct binding via N7 coordination, 2) direct binding via O6
coordination, and 3) binding via hydrogen-bonding interaction with the first
shell water molecules. In the crystal structures, the latter two modes are
associated with a buckled and propeller-twisted geometry of the basepair.
Interestingly, respective optimized geometries of these different Mg2+ binding
modes (optimized using six different DFT functionals) are consistent with their
corresponding experimental geometries. Subsequent interaction energy calculations
at the MP2 level, and decomposition of its components, suggest that for G:C W:W
Trans , Mg2+ binding can fine tune the basepair geometries without compromising
with their stability. Our results, therefore, underline the importance of the
mode of binding of Mg2+ ions in shaping RNA structure, folding and function.
PMID- 28506527
TI - Ancestral Interactions of Ribosomal RNA and Ribosomal Proteins.
AB - We have proposed that the ancient ribosome increased in size during early
evolution by addition of small folding-competent RNAs. In this Accretion Model,
small RNAs and peptides were subsumed onto subunit surfaces, gradually encasing
and freezing previously acquired components. The model predicts that appropriate
rRNA fragments have inherited local autonomy of folding and local autonomy of
assembly with ribosomal proteins (rProteins), and that the rProtein and rRNA are
co-chaperones. To test these predictions, we investigate the rRNA interactions of
rProtein uL23 and its tail, uL23tail, which is a beta-hairpin that penetrates
deep into the core of the large ribosomal subunit. In the assembled ribosome,
uL23tail associates with Domain III of the rRNA and a subdomain called
"DIIIcore". Here using band shift assays, fluorescence Job plots, and yeast three
hybrid assays, we investigate the interactions of rProtein uL23 and its tail with
Domain III and with DIIIcore rRNA. We observe rRNA1-uL23tail1 complexes in the
absence of Mg2+ ions and rRNA1-uL23tailn (n > 1) complexes in the presence of
Mg2+ ions. By contrast, the intact uL23 rProtein binds in slightly
anticooperative complexes of various stoichiometries. The globular and tail
regions of rProtein uL23 are distinctive in their folding behaviors and the ion
dependences of their association with rRNA. For the globular region of the
rProtein, folding is independent of rRNA, and rRNA association is predominantly
by nonelectrostatic mechanisms. For the tail region of the protein, folding
requires rRNA, and association is predominantly by electrostatic mechanisms. We
believe these protein capabilities could have roots in ancient evolution and
could be mechanistically important in co-chaperoning the assembly of the
ribosome.
PMID- 28506528
TI - Emerging roles of basophils in allergic inflammation.
AB - Basophils have long been neglected in immunological studies because they were
regarded as only minor relatives of mast cells. However, recent advances in
analytical tools for basophils have clarified the non-redundant roles of
basophils in allergic inflammation. Basophils play crucial roles in both IgE
dependent and -independent allergic inflammation, through their migration to the
site of inflammation and secretion of various mediators, including cytokines,
chemokines, and proteases. Basophils are known to produce large amounts of IL-4
in response to various stimuli. Basophil-derived IL-4 has recently been shown to
play versatile roles in allergic inflammation by acting on various cell types,
including macrophages, innate lymphoid cells, fibroblasts, and endothelial cells.
Basophil-derived serine proteases are also crucial for the aggravation of
allergic inflammation. Moreover, recent reports suggest the roles of basophils in
modulating adaptive immune responses, particularly in the induction of Th2
differentiation and enhancement of humoral memory responses. In this review, we
will discuss recent advances in understanding the roles of basophils in allergic
inflammation.
PMID- 28506529
TI - Guillain-Barre syndrome in a patient with renal cell carcinoma following the
first course of pazopanib therapy.
AB - Pazopanib, one of the antiangiogenic drugs, has recently become a first-line
treatment for metastatic renal cell carcinoma. The most common adverse effects of
pazopanib include diarrhea, fatigue, and nausea, but neuropathic complication has
not been documented. Here, we report the first case of a patient with metastatic
renal cell carcinoma who developed acute neuropathy mimicking Guillain-Barre
syndrome following the first course of pazopanib therapy. A 75-year-old man with
a metastatic renal cell carcinoma was admitted for rapidly progressive weakness
and numbness in the extremities after the first course of pazopanib therapy.
Neurological examination revealed symmetrical distal limb weakness, sensory
disturbance, and areflexia. Based on the clinical pictures, conduction slowing on
the nerve conduction studies of the extremities and albuminocytologic
dissociation on the cerebrospinal fluid examination, a diagnosis of Guillain
Barre syndrome was made. After discontinuation of pazopanib and a subsequent high
dose intravenous immunoglobulin therapy, symptoms rapidly resolved and the
patient became ambulatory with a cane. Serological and neuroradiological
examinations failed to reveal any possible causes for the neuropathy other than
pazopanib. While the benefits of pazopanib for metastatic renal cell carcinoma
far outweigh this neurotoxic effect, physicians prescribing this drug should be
aware of this rare complication of neuropathy.
PMID- 28506530
TI - Ipsilateral proximal and shaft femoral fractures.
AB - PURPOSE: To study the management and evaluate anatomical and functional outcomes
of patients with ipsilateral proximal and shaft femoral fractures. METHODS: A
retrospective, descriptive and analytic study lasted for ten years and a half
ranging from January 1, 2005 to June 30, 2015. The following parameters were
studied: epidemiology, fracture characteristics, therapeutic, anatomical and
functional outcomes. The correlation between different parameters was analyzed
with Fischer test. The significant threshold was defined for p value <0.05.
RESULTS: Ten medical files were registered. There were 7 men and 3 women, with a
sex ratio of 2.33. The average age was 46 years (range: 29-62 years). It was
about traffic road accidents in all cases. Motorcycle-motorcycle and motorcycle
car collision were most frequent. Average admission delay was 7 h (range: 1.5-24
h). Left side was most reached in 8 cases. According to Garden classification,
there was type III cervical fracture in 2 cases, type II in 1 case and type IV in
1 case. According to Ender classification, there was type I trochanteric fracture
in 3 cases, type VI in 2 cases and type VII in 1 case. According to AO
classification, there was type A shaft fracture in 6 cases (A2 in 4 cases and A3
in 2 cases), type B in 2 cases (B1 in 1 case and B2 in 1 case) and type C in 2
cases (C1 in 1 case and C2 in 1 case). Average surgical delay was 28.7 days
(range: 11-61 days). For proximal femoral fracture, Moore prosthesis was used in
1 case, blade plate 130 degrees in 2 cases, long Gamma nail in 4 cases, double
screwing in 2 cases and dynamic hip screw in 1 case. For shaft femoral fracture,
blade plate 95 degrees was used in 3 cases, low compressive plate in 2 cases.
Osseous contention was achieved in 4 cases with long Gamma nail and in 1 case
with long blade plate 130 degrees . Nonunion of cervical fracture was achieved in
2 cases. The average osseous healing delay was 5.14 months (range: 3-12 months)
for proximal femoral fracture and 5 months (range: 3-8 months) for shaft femoral
fractures. According to Friedman and Wyman criteria, functional results were good
in 4 cases, average in 4 cases and bad in 2 cases. Regarding implants, healing
delay showed no statistic difference between one-implant group and two-implant
group (p = 0.52), and among the patients with different functional outcomes (p =
0.52). Functional outcomes showed no statistic difference between one-implant
group and two-implant group (p = 0.46). CONCLUSION: Ipsilateral proximal and
shaft femoral fractures are relatively uncommon in our daily activities. It is
difficult to recognize proximal femoral fractures which are unnoticed. Results
are generally good if the doctors take the two fractures into account in the
management.
PMID- 28506531
TI - Parkinson's disease and pregnancy: An updated review.
AB - Pregnancy does not often occur in the setting of Parkinson's disease (PD) as the
most common age of onset is beyond the childbearing years, yet management of
these two conditions is crucial for the health of both mother and child. Here we
review treatment data of PD during pregnancy, primarily from case reports and
drug registries, and focus on available evidence regarding the pregnancy risks
for patient and fetus. Historically, it was reported that many women had
worsening of symptoms during pregnancy but this may be because anti-parkinsonian
medications were not recommended or were under dosed. Levodopa has the best
safety data for use in pregnancy and amantadine should be avoided in women who
are pregnant or trying to become pregnant. The data for other pharmacological and
surgical treatments is less clear. There is no evidence that women with PD have
higher rates of birth or fetal complications.
PMID- 28506532
TI - Accreditation of Biosafe Clinical-Grade Human Embryonic Stem Cells According to
Chinese Regulations.
AB - Human embryonic stem cells (hESCs) are promising in regenerative medicine.
Although several hESC-based clinical trials are under way, a widely accepted
standard of clinical-grade cells remains obscure. To attain a completely xeno
free clinical-grade cell line, the system must be free of xenogenic components,
the cells must have a comprehensive set of functions, and good manufacturing
practice conditions must be used. In this study, following these criteria, we
successfully derived two hESC lines, which were thereby considered "clinical
grade embryonic stem cells". In addition to the primary capacity for
pluripotency, these two cell lines were efficiently differentiated into various
types of clinical-grade progeny. Importantly, the cells were recognized by the
National Institutes for Food and Drug Control of China for further eligible
accreditation. These data indicate that we have established completely xeno-free
clinical-grade hESC lines and their derivatives, which will be valuable for the
foundation of an international standard for clinical-grade cells for therapy.
PMID- 28506534
TI - NEUROD1 Instructs Neuronal Conversion in Non-Reactive Astrocytes.
AB - Currently, all methods for converting non-neuronal cells into neurons involve
injury to the brain; however, whether neuronal transdifferentiation can occur
long after the period of insult remains largely unknown. Here, we use the
transcription factor NEUROD1, previously shown to convert reactive glial cells to
neurons in the cortex, to determine whether astrocyte-to-neuron
transdifferentiation can occur under physiological conditions. We utilized adeno
associated virus 9 (AAV9), which crosses the blood-brain barrier without injury,
to deliver NEUROD1 to astrocytes through an intravascular route. Interestingly,
we found that a small, but significant number of non-reactive astrocytes
converted to neurons in the striatum, but not the cortex. Moreover, astrocytes
cultured to minimize their proliferative potential also exhibited limited
neuronal transdifferentiation with NEUROD1 expression. Our results show that a
single transcription factor can induce astrocyte-to-neuron conversion under
physiological conditions, potentially facilitating future clinical approaches
long after the acute injury phase.
PMID- 28506533
TI - Schwann Cell Precursors from Human Pluripotent Stem Cells as a Potential
Therapeutic Target for Myelin Repair.
AB - Schwann cells play a crucial role in successful nerve repair and regeneration by
supporting both axonal growth and myelination. However, the sources of human
Schwann cells are limited both for studies of Schwann cell development and
biology and for the development of treatments for Schwann cell-associated
diseases. Here, we provide a rapid and scalable method to produce self-renewing
Schwann cell precursors (SCPs) from human pluripotent stem cells (hPSCs), using
combined sequential treatment with inhibitors of the TGF-beta and GSK-3 signaling
pathways, and with neuregulin-1 for 18 days under chemically defined conditions.
Within 1 week, hPSC-derived SCPs could be differentiated into immature Schwann
cells that were functionally confirmed by their secretion of neurotrophic factors
and their myelination capacity in vitro and in vivo. We propose that hPSC-derived
SCPs are a promising, unlimited source of functional Schwann cells for treating
demyelination disorders and injuries to the peripheral nervous system.
PMID- 28506536
TI - Checkpoint inhibition and melanoma: Considerations in treating the older adult.
AB - The incidence of melanoma and associated mortality rate from advanced disease in
older adults is increasing over time. Checkpoint inhibitors have demonstrated a
survival benefit for the treatment of stage IV or unresectable stage III disease
and have become one of the standards of care. Data suggests that adults aged 65
and older benefit from treatment with checkpoint inhibitors without an increased
incidence in adverse events. However, clinicians should be aware of the potential
side effects of this class of medications and how to manage them in older adults.
PMID- 28506537
TI - Epitope-specific immunotherapy: a vaccine for coeliac disease?
PMID- 28506535
TI - SCA-1 Expression Level Identifies Quiescent Hematopoietic Stem and Progenitor
Cells.
AB - Blood cell generation depends on continuous cellular output by the sequential
hierarchy of hematopoietic stem cell (HSC) and progenitor populations that all
contain quiescent and actively cycling cells. Hematopoietic stem and progenitor
cells (HSPCs) express the surface molecule Stem cell antigen 1 (SCA-1/LY6A).
Using histone 2B-red fluorescent fusion protein label retention and cell-cycle
reporter mice, we demonstrate that high SCA-1 expression (SCA-1hi) identifies not
only quiescent HSCs but quiescent cells on all hierarchical levels within the
lineage-SCA-1+KIT+ (LSK) population. Each transplanted SCA-1hi HSPC population
also displayed self-renewal potential superior to that of the respective SCA-1lo
population. SCA-1 expression is inducible by type I interferon (IFN). We show,
however, that quiescence and high self-renewal capacity of cells with brighter
SCA-1 expression at steady state were independent of type I IFN signaling. We
conclude that SCA-1 expression levels can be used to prospectively isolate
functionally heterogeneous HSPC subpopulations.
PMID- 28506539
TI - Description of a new soft tick species (Acari: Argasidae: Ornithodoros)
associated with stream-breeding frogs (Anura: Cycloramphidae: Cycloramphus) in
Brazil.
AB - In this study, we present a morphological description of immature and adult
specimens of Ornithodoros saraivai n. sp., a tick associated with the frog
Cycloramphus boraceiensis (Cycloramphidae) at Sao Sebastiao island, located in
the Sao Paulo state seaboard, Brazil. While larvae of O. saraivai are
ecologically related to Ornithodoros faccinii, another soft tick associated with
cycloramphids, the combination of 7 sternal pairs, 16 dorsal pairs, a pyriform
dorsal plate and a partially toothed hypostome constitute unique characters of
the O. saraivai larvae. One undetermined nymphal instar and adults of O. saraivai
are similar to mature specimens of the Ornithodoros talaje species group;
however, the O. saraivai specimens can be recognized by the presence of a robust
bean-shaped spiracle with a large spiracular plate and more than two long seta in
palpal article I. Identical partial sequences of the mitochondrial 16S rDNA gene
confirmed the identity for all collected stages and for two cohorts of laboratory
reared larvae of O. saraivai. A Bayesian and Maximum Parsimony inferred
phylogenetic trees support the position of O. saraivai in a clade with O.
faccinii, suggesting the existence of an Ornithodoros lineage that evolved in
association with amphibians.
PMID- 28506540
TI - A randomized controlled trial of an intervention program to Brazilian mothers who
use corporal punishment.
AB - This study evaluated a positive parenting program to Brazilian mothers who used
corporal punishment with their children. The intervention was conducted in four
agencies serving vulnerable children, and at a home replica laboratory at the
University. Mothers who admitted using corporal punishment were randomly assigned
between experimental (n=20) and control group (n=20). The program consisted of 12
individual sessions using one unit from Projeto Parceria (Partnership Project),
with specific guidelines and materials on positive parenting, followed by
observational sessions of mother-child interaction with live coaching and a video
feedback session in the lab. The study used an equivalent group experimental
design with pre/post-test and follow-up, in randomized controlled trials.
Measures involved: Initial Interview; Strengths and Difficulties Questionnaire
(SDQ) - parent and child versions; Beck Depression Inventory (BDI); observational
sessions with a protocol; and a Program Evaluation by participants. Analysis of
mixed models for repeated measures revealed significant positive effects on the
BDI and SDQ total scores, as well as less Conduct problems and Hyperactivity in
SDQ measures from the experimental group mothers, comparing pre with post-test.
Observational data also indicated significant improvement in positive interaction
from the experimental group mothers at post-test, in comparison with controls. No
significant results were found, however, in children's observational measures.
Limitations of the study involved using a restricted sample, among others.
Implications for future research are suggested.
PMID- 28506538
TI - Epitope-specific immunotherapy targeting CD4-positive T cells in coeliac disease:
two randomised, double-blind, placebo-controlled phase 1 studies.
AB - BACKGROUND: A gluten-free diet is the only means to manage coeliac disease, a
permanent immune intolerance to gluten. We developed a therapeutic vaccine,
Nexvax2, designed to treat coeliac disease. Nexvax2 is an adjuvant-free mix of
three peptides that include immunodominant epitopes for gluten-specific CD4
positive T cells. The vaccine is intended to engage and render gluten-specific
CD4-positive T cells unresponsive to further antigenic stimulation. We assessed
the safety and pharmacodynamics of the vaccine in patients with coeliac disease
on a gluten-free diet. METHODS: We did two randomised, double-blind, placebo
controlled, phase 1 studies at 12 community sites in Australia, New Zealand, and
the USA, in HLA-DQ2.5-positive patients aged 18-70 years who had coeliac disease
and were on a gluten-free diet. In the screening period for ascending dose
cohorts, participants were randomly assigned (1:1) by central randomisation with
a simple block method to a double-blind crossover, placebo-controlled oral gluten
challenge. Participants with a negative interferon gamma release assay to Nexvax2
peptides after the screening oral gluten challenge were discontinued before
dosing. For the biopsy cohorts, the screening period included an endoscopy, and
participants with duodenal histology who had a Marsh score of greater than 1 were
discontinued before dosing. Participants were subsequently randomly assigned to
either Nexvax2 or placebo in ascending dose cohorts (2:1) and in biopsy cohorts
(1:1) by central randomisation with a simple block method. In the three-dose
study, participants received either Nexvax2 60 MUg, 90 MUg, or 150 MUg weekly, or
placebo over 15 days; in a fourth biopsy cohort, patients received either Nexvax2
at the maximum tolerated dose (MTD) or placebo. In the 16-dose study,
participants received Nexvax2 150 MUg or 300 MUg or placebo twice weekly over 53
days; in a third biopsy cohort, patients also received either Nexvax2 at the MTD
or placebo. In the 4-week post-treatment period, ascending dose cohorts underwent
a further double-blind crossover, placebo-controlled oral gluten challenge, which
had a fixed sequence, and biopsy cohorts had a gastroscopy with duodenal biopsies
and quantitative histology within 2 weeks without oral gluten challenge.
Participants, investigators, and study staff were masked to the treatment
assignment, except for the study pharmacist. The primary endpoint was the number
and percentage of adverse events in the treatment period in an intention-to-treat
analysis. Both trials were completed and closed before data analysis. Trials were
registered with the Australian New Zealand Clinical Trials Registry, numbers
ACTRN12612000355875 and ACTRN12613001331729. FINDINGS: Participants were enrolled
from Nov 28, 2012, to Aug 14, 2014, in the three-dose study, and from Aug 3,
2012, to Sept 10, 2013, in the 16-dose study. Overall, 62 (57%) of 108
participants were randomly assigned after oral gluten challenge and 20 (71%) of
28 participants were randomly assigned after endoscopy. In the three-dose study,
nine participants were randomly allocated to Nexvax2 60 MUg and three to placebo
(first cohort), nine were allocated to Nexvax2 90 MUg and four to placebo (second
cohort), eight were allocated to Nexvax2 150 MUg and four to placebo (third
cohort), and three were allocated to Nexvax2 150 MUg and three to placebo (biopsy
cohort). In the 16-dose study, eight participants were randomly allocated to
Nexvax2 150 MUg and four to placebo (first cohort), ten were allocated to Nexvax2
300 MUg and three to placebo (second cohort), and seven were allocated to Nexvax2
150 MUg and seven to placebo (biopsy cohort). The MTD for Nexvax2 was 150 MUg
because of transient, acute gastrointestinal adverse events with onset 2-5 h
after initial doses of the vaccine, similar to those caused by gluten ingestion.
In the ascending dose cohorts in the three-dose study, six (55%) of 11 placebo
recipients, five (56%) of nine who received Nexvax2 60 MUg, seven (78%) of nine
who received Nexvax2 90 MUg, and five (63%) of eight who received Nexvax2 150 MUg
had at least one treatment-emergent adverse event, as did all three (100%)
placebo recipients and one (33%) of three Nexvax2 150 MUg recipients in the
biopsy cohort. In the ascending dose cohorts of the 16-dose study, five (71%) of
seven placebo-treated participants, six (75%) of eight who received Nexvax2 150
MUg, and all ten (100%) who received Nexvax2 300 MUg had at least one treatment
emergent adverse event, as did six (86%) of seven placebo recipients and five
(71%) of seven Nexvax2 150 MUg recipients in the biopsy cohort. Vomiting, nausea,
and headache were the only treatment-emergent adverse events that occurred in at
least 5% of participants in either study. Among participants given the MTD, eight
gastrointestinal treatment-emergent adverse events occurred in four (50%) of
eight participants in the third cohort and none (0%) of three participants in the
biopsy cohort in the three-dose study, and five events occurred in five (63%) of
eight participants in the first cohort and three events in two (29%) of seven
participants in the biopsy cohort of the 16-dose study. Median villous height to
crypt depth ratio in distal duodenal biopsies was not significantly different
between those who received the vaccine at the MTD on either schedule and those
who received placebo. Of the participants who completed the post-treatment oral
gluten challenge per protocol, interferon gamma release assay to Nexvax2 peptides
was negative (responders to treatment) in two (22%) of nine placebo-treated
participants in the three-dose study versus two (33%) of six who received Nexvax2
60 MUg, five (63%) of eight who received Nexvax2 90 MUg, and six (100%) of six
who received Nexvax2 150 MUg (p=0.007); in the 16-dose study, none (0%) of five
placebo-treated participants had a negative assay versus six (75%) of eight who
received Nexvax2 150 MUg (p=0.021). INTERPRETATION: The MTD of Nexvax2 was 150
MUg for twice weekly intradermal administration over 8 weeks, which modified
immune responsiveness to Nexvax2 peptides without deterioration in duodenal
histology. The gastrointestinal symptoms that followed the first intradermal
administration of the vaccine resembled those associated with oral gluten
challenge. These findings support continued clinical development of this
potential therapeutic vaccine for coeliac disease. FUNDING: ImmusanT.
PMID- 28506541
TI - Mitral Regurgitation Grading in the Operating Room: A Systematic Review and Meta
analysis Comparing Preoperative and Intraoperative Assessments During Cardiac
Surgery.
AB - OBJECTIVE: To assess differences in mitral regurgitation (MR) grade between the
preoperative and the intraoperative evaluations. DESIGN: Systematic review and
meta-analysis of 6 observational studies found from MEDLINE and EMBASE. SETTING:
Cardiac surgery. PARTICIPANTS: One hundred thirty-seven patients. INTERVENTION:
Comparison between the preoperative MR assessment and the intraoperative
evaluation conducted under general anesthesia (GA), with or without "hemodynamic
matching" (HM) (artificial increase of afterload). MEASUREMENTS AND MAIN RESULTS:
The primary outcome was the difference between the preoperative and
intraoperative MR grade under "GA-only" or "after-HM." Secondary analyses
addressed differences according to effective regurgitant orifice area (EROA),
regurgitant volume (RVol), color-jet area, and vena contracta width. Risk of MR
underestimation was found under "GA-only" (SMD: 0.55; 95% confidence interval
[CI], 0.31-0.79, p < 0.00001), but not "after-HM" (SMD: -0.16; 95% CI, -0.46 to
0.13, p = 0.27). Under "GA-only", EROA had a trend toward underestimation (p =
0.07), RVol was reliable (p = 0.17), while reliance on color-jet area and vena
contracta width incur risk of underestimation (both p = 0.003). After HM, EROA
accurately reflected preoperative MR (p = 0.68) while RVol had a trend toward
overestimation (p = 0.05). The overall reported incidence of misdiagnoses was
slightly more common under "GA-only" (mean 48%, 39% underestimation, 9%
overestimation; range: 32%-57%) than "after-HM" (mean 41%, 12% underestimation,
29% overestimation; range: 33%-50%). Only the minority of misdiagnoses were
clinically relevant: underestimation was around 10% (both approaches), but 18%
had clinically significant overestimation "after-HM" as compared with 3% under GA
only. CONCLUSIONS: Intraoperative assessment under "GA-only" significantly
underestimated MR. A more accurate intraoperative evaluation can be obtained with
afterload manipulation, although HM strategy carries high risk of clinically
significant overestimation.
PMID- 28506542
TI - Coronary Sinus Isoflurane Concentration in Cardiac Surgery.
AB - OBJECTIVE: Volatile anesthetic agents such as isoflurane may be associated with
fewer adverse myocardial events compared with total intravenous anesthesia in
cardiac surgery. The authors aimed to determine whether reasonable isoflurane
concentrations at tissue level were being achieved to protect the myocardium
using this agent. The isoflurane concentration in myocardium has never been
measured. The primary aim was to sample coronary sinus (CS) blood and measure its
isoflurane concentration. Secondary aims were to determine whether the CS blood
concentration would equilibrate with the arterial blood concentration and the
relationship of CS blood concentration with oxygenator exhaust isoflurane
concentrations during cardiopulmonary bypass (CPB). DESIGN: Prospective,
observational study. SETTING: Single-center university hospital. PARTICIPANTS:
The study comprised 23 patients undergoing cardiac surgery using CPB and
isoflurane. MEASUREMENTS AND MAIN RESULTS: Shortly after initiation of CPB and
insertion of a CS retrograde cardioplegia catheter but before aortic cross
clamping, CS blood was aspirated, followed by radial artery blood, which then
were analyzed for isoflurane with gas chromatography and mass spectrometry. The
oxygenator exhaust isoflurane level was measured with an anesthetic gas analyzer.
The mean arterial and CS isoflurane concentrations were 87.7 +/- 50.1 and 73.0 +/
42.9 MUg/mL, respectively. There was a significant mean difference of 14.7
MUg/mL (95% confidence interval 6.7-22.8) between CS and arterial isoflurane
concentrations. Oxygenator exhaust isoflurane levels were correlated positively
with those in the CS blood (r = 0.68, p < 0.001) and arterial blood (r = 0.72, p
< 0.001). CONCLUSIONS: This was the first study in which CS blood was sampled and
measured for isoflurane concentration. The CS isoflurane concentration could be
estimated from the isoflurane concentration in the oxygenator exhaust gas.
However, the value of this relationship is limited because the CS isoflurane
concentration does not accurately represent its myocardial levels during CPB.
PMID- 28506543
TI - Implementing a pharmacist-led, individualized medication assessment and planning
(iMAP) intervention to reduce medication related problems among older adults with
cancer.
AB - OBJECTIVES: Medication-related problems (MRP) affecting older adults are a
significant healthcare concern and account for billions in medication-related
morbidity. Cancer therapies can increase the prevalence of MRP. The objective of
this study was to test the feasibility and effectiveness of implementing a
pharmacist-led individualized medication assessment and planning (iMAP)
intervention on the number and prevalence of MRP. MATERIALS AND METHODS: This
prospective pilot study enrolled oncology outpatients aged >=65years.
Intervention feasibility encompassed recommendation acceptance rate and
intervention delivery time. The intervention was facilitated by pharmacists where
patients received comprehensive medication management at baseline and at the 30-
and 60-day follow-up. RESULTS: Forty-eight eligible patients enrolled and 41
patients (85.4%) were included in the analysis. Mean age was 79.1years [range 65
101]; 66% women, 83% Caucasian, mean comorbidity count was 7.76. Forty-six
percent of the pharmacist recommendations were accepted and the prevalence of MRP
at baseline versus 60-day follow-up decreased by 20.5%. The average time to
conduct the initial session was 22min versus 15min for the follow-up sessions.
Resources needed included a tracking system for scheduling follow-up calls and a
database for tracking acceptance of recommendations. A total of 123 MRP were
identified in 95% of patients (N=39) with a mean of 3 MRP per patient. The mean
reduction in number of MRP (3 at baseline versus 1.6 at 60-day follow-up) was
45.5%. CONCLUSIONS: The pharmacist-led iMAP intervention was feasible and
effective at reducing MRP. Additional inter-professional medication safety based
interventions measuring patient-reported outcomes are still needed.
PMID- 28506545
TI - Travel for Abortion Services in Alabama and Delays Obtaining Care.
AB - BACKGROUND: In 2013, Alabama required women seeking abortion to have a
consultation visit followed by a 24-hour waiting period. These requirements may
adversely affect return for timely care among those traveling long distances for
services. METHODS: Using de-identified billing data from two Alabama clinics for
all abortion encounters in 2013, we calculated the distance traveled from women's
residential zip code and the number of days between their in-person consultation
and procedure visits. To assess the associations between distance traveled and
return for an abortion visit and length of interval between visits, we used
logistic and ordinal logistic regression, respectively. RESULTS: Of the 2,730
women attending a consultation visit, 58% traveled less than 25 miles one way to
the clinic, 13% traveled 25 to 49 miles, 21% traveled 50 to 100 miles, and 8%
traveled more than 100 miles. Overall, 19% of women did not return to either
clinic for an abortion procedure after their consultation. Distance traveled was
not associated with return for an abortion visit (odds ratio, 1.04; 95%
confidence interval, 0.76-1.42). Among women who returned, 59% had less than 7
days, 29% had 7 to 13 days, and 12% had 14 or more days between their
consultation and procedure visits. Compared with women traveling less than 25
miles, those traveling 50 to 100 miles had significantly longer intervals between
visits (odds ratio, 1.25; 95% confidence interval, 1.01-1.56). CONCLUSIONS:
Although most women returned for their abortion procedure, many traveling long
distances had a week or more between visits. Because delays may limit women's
options for affordable abortion care, evidence-based policies should be adopted
to facilitate women's timely receipt of services.
PMID- 28506544
TI - Development of the Vanderbilt Assessment for Delirium in Infants and Children to
Standardize Pediatric Delirium Assessment By Psychiatrists.
AB - BACKGROUND: Pediatric delirium assessment is complicated by variations in
baseline language and cognitive skills, impairment during illness, and absence of
pediatric-specific modifiers within the Diagnostic and Statistical Manual of
Mental Disorders delirium criterion. OBJECTIVE: To develop a standardized
approach to pediatric delirium assessment by psychiatrists. METHODS: A
multidisciplinary group of clinicians used Diagnostic and Statistical Manual
criterion as the foundation for the Vanderbilt Assessment for Delirium in Infants
and Children (VADIC). Pediatric-specific modifiers were integrated into the
delirium criterion, including key developmental and assessment variations for
children. The VADIC was used in clinical practice to prospectively assess
critically ill infants and children. The VADIC was assessed for content validity
by the American Academy of Child and Adolescent Psychiatry Delirium Special
Interest Group. RESULTS: The American Academy of Child and Adolescent Psychiatry
Delirium Special Interest Group determined that the VADIC demonstrated high
content validity. The VADIC (1) preserved the core Diagnostic and Statistical
Manual delirium criterion, (2) appropriately paired interactive assessments with
key criterion based on development, and (3) addressed confounders for delirium. A
cohort of 300 patients with a median age of 20 months was assessed for delirium
using the VADIC. Delirium prevalence was 47%. CONCLUSION: The VADIC provides a
comprehensive framework to standardize pediatric delirium assessment by
psychiatrists. The need for consistency in both delirium education and diagnosis
is highlighted given the high prevalence of pediatric delirium.
PMID- 28506546
TI - A Model for Electronic Handoff Between the Emergency Department and Inpatient
Units.
AB - BACKGROUND: Patient handoffs between units can introduce risk and time delays.
Verbal communication is the most common mode of handoff, but requires
coordination between different parties. OBJECTIVE: We present an asynchronous
patient handoff process supported by a structured electronic signout for
admissions from the emergency department (ED) to the inpatient medicine service.
METHODS: A retrospective review of patients admitted to the medical service from
July 1, 2011 to June 30, 2015 at a tertiary referral center with 520 inpatient
beds and 57,000 ED visits annually. We developed a model for structured
electronic, asynchronous signout that includes an option to request verbal
communication after review of the electronic handoff information. RESULTS: During
the 2010 academic year (AY) all admissions used verbal communication for signout.
The following academic year, electronic signout was implemented and 77.5% of
admissions were accepted with electronic signout. The rate increased to 87.3% by
AY 2014. The rate of transfer from floor to an intensive care unit within 24 h
for the year before and 4 years after implementation of the electronic signout
system was collected and calculated with 95% confidence interval. There was no
statistically significant difference between the year prior and the years after
the implementation. CONCLUSIONS: Our handoff model sought to maximize the
opportunity for asynchronous signout while still providing the opportunity for
verbal signout when deemed necessary. The process was rapidly adopted with the
majority of patients being accepted electronically.
PMID- 28506547
TI - Transcatheter mitral valve interventions for mitral regurgitation, with special
focus on MitraClip: The position of Spanish, Portuguese and Italian
interventional societies.
AB - Mitral regurgitation is a common valvular heart disease and its prevalence is
expected to increase with population ageing. In the recent years we have
witnessed the evolution of several transcatheter devices to correct mitral
regurgitation in patients at high-risk for surgery. Most of the evidence of the
safety and efficacy of this new therapy comes from MitraClip studies. However,
new alternatives have emerged with promising results. The aim of this position
paper is to review the current evidence regarding patient selection, expected
results and timing for transcatheter mitral valve interventions from the
perspective of three European interventional societies.
PMID- 28506549
TI - Impact of chronic obstructive pulmonary disease on in-hospital morbidity and
mortality in patients with ST-segment elevation myocardial infarction treated by
primary percutaneous coronary intervention.
AB - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) presenting
with ST-segment elevation myocardial infarction (STEMI) are less likely to
beneficiate of primary percutaneous coronary intervention (pPCI), and have poorer
prognosis. We aimed to evaluate the impact of COPD on the in-hospital outcomes of
pPCI-treated STEMI patients. METHODS: Data were collected from 418 STEMI patients
treated by pPCI. Inotropics and diuretics usage, cardiogenic shock, asystole,
kidney dysfunction, and left ventricular ejection fraction were used as markers
of hemodynamic complications. Atrial and ventricular fibrillation, conduction
disorders, and antiarrhythmics usage were used as markers of arrhythmic
complications. In-hospital mortality was evaluated. The associations between
these parameters and COPD were assessed. RESULTS: COPD was present in 7.42% of
STEMI patients. COPD patients were older (p=0.02) and less likely to receive beta
blockers (OR 0.29; 95%CI 0.13-0.64; p<0.01). They had higher Killip class on
admission (p<0.001), received more often inotropics (p<0.001) and diuretics
(p<0.01), and presented more often atrial (p=0.01) and ventricular fibrillation
(p=0.02). Unadjusted in-hospital mortality was higher in COPD patients (OR 4.18,
95%CI 1.55-11.30, p<0.01). After adjustment for potentially confounding factors
except beta-blockers, COPD remained an independent predictor of in-hospital
mortality (p=0.02). After further adjustment with beta-blocker therapy, no excess
mortality was noted in COPD patients. CONCLUSIONS: Despite being treated by pPCI,
COPD patients with STEMI are more likely to develop hemodynamic and arrhythmic
complications, and have higher in-hospital mortality. This appears to be due to
lower beta-blockers usage in COPD patients. Increasing beta-blockers usage in
COPD patients with STEMI may improve survival.
PMID- 28506548
TI - Antiarrhythmic medication is superior to catheter ablation in suppressing
supraventricular ectopic complexes in patients with atrial fibrillation.
AB - BACKGROUND: Supraventricular ectopic complexes (SVEC) originating in the
pulmonary veins are known triggers of atrial fibrillation (AF) which led to the
development of pulmonary vein isolation for AF. However, the long-term prevalence
of SVEC after catheter ablation (CA) as compared to antiarrhythmic medication
(AAD) is unknown. Our aims were to compare the prevalence of SVEC after AAD and
CA and to estimate the association between baseline SVEC burden and AF burden
during 24months of follow-up. METHODS: Patients with paroxysmal AF (N=260)
enrolled in the MANTRA PAF trial were treated with AAD (N=132) or CA (N=128). At
baseline and 3, 6, 12, 18 and 24months follow-up patients underwent 7-day Holter
monitoring to assess SVEC and AF burden. We compared SVEC burden between
treatments with Wilcoxon sum rank test. RESULTS: Patients treated with AAD had
significantly lower daily SVEC burden during follow-up as compared to CA (AAD: 19
[6-58] versus CA: 39 [14-125], p=0.003). SVEC burden increased post-procedurally
followed by a decrease after CA whereas after AAD SVEC burden decreased and
stabilized after 3months of follow-up. Patients with low SVEC burden had low AF
burden after both treatments albeit this was more pronounced after CA at 24months
of follow-up. CONCLUSION: AAD was superior to CA in suppressing SVEC burden after
treatment of paroxysmal AF. After CA SVEC burden increased immediately post
procedural followed by a decrease whereas after AAD an early decrease was
observed. Lower SVEC burden was highly associated with lower AF burden during
follow-up especially after CA.
PMID- 28506551
TI - Early in-hospital variation of red blood cell distribution width predicts
mortality in patients with acute heart failure.
AB - BACKGROUND: Some studies showed that the value of red blood cell distribution
width (RDW) at admission may predict clinical outcomes in patients with acutely
decompensated heart failure (ADHF). Therefore, this study was planned to
investigate whether in-hospital variations of RDW may also predict mortality in
this condition. METHODS: The final study population consisted of 588 patients
admitted to the local Emergency Department (ED), who were hospitalized for ADHF.
The RDW was measured at ED admission and after 48h and 96h of hospital stay. In
hospital variations from admission value, expressed as absolute variation
(DeltaRDW) or percent variation (Delta%RDW), were then correlated with 30- and 60
day mortality. RESULTS: Overall, 87 (14.8%) and 118 (20.1%) patients with ADHF
died at 30 or 60days of follow-up. Delta%RDW after 96h of hospital stay
independently predicted 30-day mortality (odds ratio, 1.12; 95% CI, 1.07-1.18).
An increase >1% of Delta%RDW after 96h of hospital stay independently predicted
both 30-day (odds ratio, 2.86; 95% CI, 1.67-4.97) and 60-day (odds ratio, 3.06;
95% CI, 1.89-4.96) mortality. A similar trend was observed for DeltaRDW, since an
increase after 96h of hospital stay was associated with a nearly 4-fold higher 30
day mortality (odds ratio, 3.65; 95% CI, 2.02-6.15). CONCLUSION: Despite it
remains unclear whether RDW is a real risk factor or an epiphenomenon in ADHF,
these results suggest that more aggressive management may be advisable in ADHF
patients with increasing anisocytosis during the first days of hospitalization.
PMID- 28506550
TI - Cardioprotective efficacy of sevoflurane vs. propofol during induction and/or
maintenance in patients undergoing coronary artery revascularization surgery
without pump: A randomized trial.
AB - PURPOSE: Pre and post-operative administration of sevoflurane in myocardial
revascularization surgery provides enhanced cardioprotective effects exerted by
pharmacologic pre- and post-conditioning, as compared to propofol. The
identification of the enzymes involved in conditioning mechanisms is crucial to
the understanding of the effects of sevoflurane in cardiac surgery patients. The
impact of sevoflurane on another crucial target organ-the kidney-was also
assessed. METHODS: Ninety patients undergoing off-pump myocardial
revascularization surgery were allocated to receive either intra- and
postoperative sevoflurane (SS), intraoperative sevoflurane and postoperative
propofol (SP), or intra- and postoperative propofol (PP)). Troponin I and
hemodynamic parameters were monitored during the first 48 postoperative hours;
blood and urine samples were collected at baseline and at 24h to determine Akt,
ERK1/2, PKG, iNO, bradykinin receptor, caspase 3, NT proBNP and urinary NGAL.
RESULTS: The enzymes were overexpressed in the SS group, remained unchanged in
the SP group, and decreased in the PP group. Renal function was best preserved in
the SS group. CONCLUSIONS: The overexpression of enzymes induced by
intraoperative anesthesia and postoperative sedation with sevoflurane reduces
myocardial damage and improves renal function in patients undergoing off-pump
myocardial revascularization surgery.
PMID- 28506552
TI - The natural terthiophene alpha-terthienylmethanol induces S phase cell cycle
arrest of human ovarian cancer cells via the generation of ROS stress.
AB - Ovarian cancer is the most lethal gynecological malignancy worldwide. Thiophenes
such as terthiophene have been shown to have anti-tumor effects on several cancer
cell lines, including ovarian cancer cells. However, the underlying mechanisms
behind the anti-proliferative effect of thiophenes are poorly understood. In this
study, we investigated the molecular mechanisms underlying the anti-proliferative
effect of alpha-terthienylmethanol, a terthiophene isolated from Eclipta
prostrata (False Daisy), on human ovarian cancer cells. We found that alpha
terthienylmethanol is a more potent inhibitor of cell growth than is cisplatin in
human ovarian cancer cells. alpha-Terthienylmethanol induces cell cycle arrest in
ovarian cancer cells, as shown by the accumulation of cells in S phase. In
addition, alpha-terthienylmethanol induced a change in S phase-related proteins
cyclin A, cyclin-dependent kinase 2, and cyclin D2. Knockdown of cyclin A using
specific siRNAs significantly compromised alpha-terthienylmethanol-induced S
phase arrest. We further demonstrated that alpha-terthienylmethanol induced an
increase in intracellular ROS, and the antioxidant N-acetyl-l-cysteine
significantly reversed the S phase arrest induced by alpha-terthienylmethanol.
Moreover, alpha-terthienylmethanol significantly increased the levels of p-H2AX,
a DNA damage marker. These results suggest that alpha-terthienylmethanol inhibits
the growth of human ovarian cancer cells by S phase cell cycle arrest via
induction of ROS stress and DNA damage.
PMID- 28506553
TI - Inhibition of 12/15-LO ameliorates CVB3-induced myocarditis by activating Nrf2.
AB - Cardiac 12/15-lipoxygenase (12/15-LO) was reported to be markedly up-regulated
and involved in the development of heart failure. Nuclear factor E2-related
factor 2 (Nrf2) plays anti-inflammatory and anti-oxidation roles in response to
oxidative stress. However, the role of 12/15-LO in viral myocarditis (VMC) and
its underlying molecular mechanism have not yet been elucidated. Here, we
demonstrated that 12/15-LO was up-regulated and Nrf2 was down-regulated in
coxsackievirus B3 (CVB3)-infected mice and cardiac myocytes. Baicalein, the
specific inhibitor of 12/15-LO, was employed to investigate the role of 12/15-LO
and its underlying mechanism in VMC. We found that baicalein treatment alleviated
CVB3-induced VMC mouse models, as demonstrated by less inflammatory lesions in
the heart tissues and less CK-MB level. Moreover, baicalein treatment attenuated
CVB3-induced inflammatory cytokine production and oxidative stress. Mechanistic
analysis suggested that baicalein treatment relieved CVB3-induced reduction of
Nrf2 and heme oxygenase-1 (HO-1) expressions. Taken together, our study indicated
that inhibition of 12/15-LO ameliorates VMC by activating Nrf2, providing a new
therapeutic strategy for the therapy of VMC.
PMID- 28506554
TI - Selective dopamine receptor 4 activation mediates the hippocampal neuronal
calcium response via IP3 and ryanodine receptors.
AB - Intracellular calcium is a key factor in most cellular processes, including cell
growth, differentiation, proliferation and neurotransmitter release. Dopamine
(DA) mediates synaptic transmission by regulating the intracellular calcium
content. It is not clear, however, which specific subunit of the DA receptor
contributes to DA modulation of intracellular calcium content changes. Through
the traditional technique of Fura-2 calcium imaging, this study demonstrated that
the DA can induce transient calcium in cultured hippocampal neurons and that this
response can be mimicked by a selective dopamine receptor 4 (DR4) agonist
PD168077 (PD). PD-induced calcium transience can be blocked by a calcium
chelator, such as BAPTA-AM, or by pre-treatment of neurons with thapsigargin, a
IP3 receptor antagonist, or a micromolar concentration of ryanodine, a ryanodine
receptor (RyR) antagonist. However PD-induced calcium transience cannot be
blocked by pre-treatment of neurons with a free-calcium medium or a cocktail of
NMDA receptor, L-type calcium channel and alpha7 nicotinic acetylcholine receptor
blockers. These results indicate that the calcium response induced by DR4
activation is mainly through activation of IP3 receptor in internal stores, which
is likely to contribute to the DA modulation of synaptic transmission and
cognitive function.
PMID- 28506555
TI - Gut microbiota in Parkinson disease in a northern German cohort.
AB - Pathologic and epidemiologic studies suggest that Parkinson disease (PD) may in
some cases start in the enteric nervous system and spread via the vagal nerve to
the brainstem. Mounting evidence suggests that the gut microbiome plays an
important role in the communication between gut and brain and that alteration of
the gut microbiome is involved in the pathogenesis of numerous diseases,
including Parkinson disease. The aim of this study was to determine whether
Parkinson disease is associated with qualitative or quantitative changes in the
gut microbiome. We analyzed the gut microbiome in 29 PD cases and 29 age-matched
controls by next-generation-sequencing of the 16S rRNA gene and compared
diversity indices and bacterial abundances between cases and controls. Alpha
diversity measures and the abundance of major phyla did not differ between cases
and controls. Beta diversity analyses and analysis on the bacterial family level
revealed significant differences between cases and controls for four bacterial
families. In keeping with recently published studies, Lactobacillaceae were more
abundant in cases. Barnesiellaceae and Enterococcacea were also more abundant in
cases in this study but not in other studies. Larger studies, accounting for drug
effects and further functional investigations of the gut microbiome are necessary
to delineate the role of the gut microbiome in the pathogenesis of PD.
PMID- 28506556
TI - Pfizer to make palbociclib temporarily free on NHS.
PMID- 28506558
TI - Switch to exemestane effective in early breast cancer.
PMID- 28506557
TI - Brigatinib effective in ALK-positive non-small-cell lung cancer.
PMID- 28506559
TI - A novel electron mirror pulse compressor.
AB - An electron mirror-based pulse compressor design has been developed for improving
the temporal resolution of dynamic/ultrafast transmission electron microscopes
and ultrafast electron diffraction cameras. The improvement will enable electron
microscopes and diffraction cameras to better resolve the dynamics of reactions
in the areas of solid state physics, chemistry, and biology. The design utilizes
a combination of mirror optics and a magnetic beam separator, which exploits the
symmetry inherent in reversing the electron trajectory in the mirror in order to
compress the pulse. This system can also simultaneously correct the spherical and
chromatic aberration of the objective lens for improved spatial resolution. For
pulsed experiments with a practical bunch charge, the correction of the chromatic
aberration coefficient counters the spread in the electron energies induced by
the space charge of the pulse to make possible the probing of the sample with
high spatial resolution. The pulse compressor can accommodate pulses with a range
of electron densities and energy spreads. Furthermore, it is designed to fit into
both ultrafast electron diffraction cameras and dynamic/ultrafast transmission
electron microscopes. Consequently, this instrument is suitable for enhancing the
study of the structure, composition, and bonding states of new materials at
ultrafast time scales.
PMID- 28506560
TI - A Rare Clinical Entity in Bladder Cancer: Paraneoplastic Cerebellar Degeneration.
PMID- 28506561
TI - The Consequences of Real Life Practice of Early Abdominal Aortic Aneurysm Repair:
A Cost-Benefit Analysis.
AB - BACKGROUND: The reported 54 mm median intervention diameter for endovascular
aneurysm repair (EVAR) in the Vascular Quality Initiative and European data from
the Pharmaceutical Aneurysm Stabilisation Trial (PHAST) implies that in real life
the majority of abdominal aortic aneurysm (AAA) repairs occur at diameters
smaller than the consensus intervention threshold of 55 mm. This study explores
the potential consequences of this practice. METHODS: The differences between
real life AAA repair and consensus based intervention threshold were explored in
reported data from vascular quality initiatives and PHAST. The subsequent
consequences of advancement of endovascular aneurysm repair (EVAR) were estimated
using a multistate model based on life tables for the EVAR Medicare population.
RESULTS: There appears an approximate 5 mm difference in AAA diameter between
real life practice and consensus intervention threshold. Assuming a 2.5 mm annual
growth rate, this results in an approximately 2 year advancement of AAA repair.
According to the model used, early repair reduces overall small aneurysm patient
mortality by 2.3%, it results in 21.9% more EVAR procedures, more EVAR related
deaths, and 42.3% and 36.8% more open and endovascular re-interventions,
respectively. Cost-benefit estimates imply 482 fewer AAA related deaths, but 140
extra EVAR related deaths for a population of more than 30,000 AAA patients, and
a 300 million USD increase in health costs for the 8 year observation period in
the Medicare population. CONCLUSIONS: In the real life situation a large
proportion of EVAR procedures appear to occur before reaching the consensus
threshold. Although this reduces mortality, it comes at a cost of approximately 1
million USD per prevented rupture related death.
PMID- 28506562
TI - The Impact of System Factors on Quality and Safety in Arterial Surgery: A
Systematic Review.
AB - OBJECTIVE: A systems approach to patient safety proposes that a wide range of
factors contribute to surgical outcome, yet the impact of team, work environment,
and organisational factors, is not fully understood in arterial surgery. The aim
of this systematic review is to summarize and discuss what is already known about
the impact of system factors on quality and safety in arterial surgery. DATA
SOURCES: A systematic review of original research papers in English using
MEDLINE, Embase, PsycINFO, and Cochrane databases, was performed according to
PRISMA guidelines. REVIEW METHODS: Independent reviewers selected papers
according to strict inclusion and exclusion criteria, and using predefined data
fields, extracted relevant data on team, work environment, and organisational
factors, and measures of quality and/or safety, in arterial procedures. RESULTS:
Twelve papers met the selection criteria. Study endpoints were not consistent
between papers, and most failed to report their clinical significance. A variety
of tools were used to measure team skills in five papers; only one paper measured
the relationship between team factors and patient outcomes. Two papers reported
that equipment failures were common and had a significant impact on operating
room efficiency. The influence of hospital characteristics on failure-to-rescue
rates was tested in one large study, although their conclusions were limited to
the American Medicare population. Five papers implemented changes in the patient
pathway, but most studies failed to account for potential confounding variables.
CONCLUSIONS: A small number of heterogenous studies have evaluated the
relationship between system factors and quality or safety in arterial surgery.
There is some evidence of an association between system factors and patient
outcomes, but there is more work to be done to fully understand this
relationship. Future research would benefit from consistency in definitions, the
use of validated assessment tools, measurement of clinically relevant endpoints,
and adherence to national reporting guidelines.
PMID- 28506563
TI - Challenges to delivery and effectiveness of adjuvant radiation therapy in elderly
patients with node-positive vulvar cancer.
AB - OBJECTIVE: To examine adjuvant radiation therapy (RT) use, patterns of RT
delivery, and clinical outcomes in older patients with node-positive vulvar
cancer. METHODS: Using SEER-Medicare linked data, we identified 444 patients
(age>=66years) with node-positive squamous cell vulvar carcinoma, without distant
metastases, and treated with primary surgery between 1991 and 2009. We used
claims to examine RT use and the following delivery metrics: 1) completion of
>=20 fractions, 2) treatment duration <8weeks, 3) <1week of intra-treatment
break, and 4) treatment interval from surgery to start of RT <8weeks. We tested
associations between RT use and metrics with overall (OS) and cause-specific
survival (CSS) using multivariate proportional hazards regression. RESULTS:
Median age was 78years (interquartile range [IQR]=74-83). Median follow-up was
17months (IQR=9-40). Three hundred six patients (69%) received RT. Three delivery
metrics were associated with improved outcomes: completion of >=20 fractions,
treatment duration <8weeks, and <1week of intra-treatment break. Patients who
achieved these 3 metrics demonstrated better disease outcomes compared with
surgery alone (OS hazard ratio [HR] for death=0.62, 95% confidence interval
[CI]=0.46-0.82, P=0.001; CSS HR=0.58, 95% CI=0.40-0.85,P=0.005). Patients not
achieving RT metrics demonstrated marginal improvements in disease outcomes over
surgery alone (OS HR=0.73, 95% CI=0.55-0.99,P=0.04; CSS HR=0.76, 95% CI=0.52
1.11, P=0.16). Notably, only 51% of patients who received RT achieved all
benchmarks. CONCLUSIONS: In this cohort of older women with node-positive vulvar
cancer, achieving metrics for RT delivery was an important factor for optimizing
disease benefits from treatment.
PMID- 28506564
TI - Contamination of cockroaches (Insecta: Blattaria) to medically fungi: A
systematic review and meta-analysis.
AB - INTRODUCTION: Fungal infections have emerged worldwide. Cockroaches have been
proved vectors of medically fungi. METHODS: A systematic meta-analysis review
about cockroach fungal contamination was investigated. Relevant topics were
collected between January 2016 and January 2017. After a preliminary review among
392 collected papers, 156 were selected to become part of the detailed systematic
meta-analysis review. RESULTS: Cockroaches contaminated to 38 fungi species
belonging to 19 families and 12 orders. About 38, 25 and 13 fungal species were
recovered from the American, German and brown-banded cockroaches, respectively
with a variety of medical importance. Except the fungi isolated from German and
brown-banded cockroaches, 15 species have been isolated only from the American
cockroaches. The global world mean and trend of cockroach fungal contamination
were 84.1 and 50.6-100%, respectively in the human dwelling environments. There
is a significant difference between cockroach fungal contamination in the urban
and rural environments (P<0.05) without a significant difference between hospital
and household environments (P>0.05). The external and internal cockroach fungal
contamination is more dangerous than entire surfaces, while the internal is more
dangerous than the external surface. The German and brown-banded cockroach fungal
contamination are more dangerous than the American cockroaches in the hospital
environments. CONCLUSION: The study indicates that globally cockroach fungal
contamination has been increased recognizing as agents of human infections and
associating with high morbidity and mortality in immune-compromised patients.
These facts, along with insecticide resistance emergence and increasing globally
cockroach infestation, reveal importance of cockroaches and need for their
control more than ever.
PMID- 28506565
TI - The antifungal activity of Moroccan plants and the mechanism of action of
secondary metabolites from plants.
AB - This review is based on a comprehensive literature search for existing knowledge
about antifungal mechanisms of different secondary metabolites from plants. The
secondary metabolites have been grouped into three major groups according to
their biosynthetic origin. On another side, this review represents studies on
antifungal activity of essential oils and extracts from Moroccan plants, against
fungal species involved in human or plant diseases.
PMID- 28506566
TI - Trends in racial/ethnic disparities of new AIDS diagnoses in the United States,
1984-2013.
AB - PURPOSE: In the United States, human immunodeficiency virus (HIV)/acquired immune
deficiency syndrome (AIDS) disproportionately impacts racial/ethnic minorities.
We describe and evaluate trends in the Black-White and Hispanic-White disparities
of new AIDS diagnoses from 1984 to 2013 in the United States. METHODS: AIDS
diagnosis rates by race/ethnicity for people >=13 years were calculated using
national HIV surveillance and Census data. Black-White and Hispanic-White
disparities were measured as rate ratios. Joinpoint Regression was used to
identify time periods across which to estimate rate-ratio trends. We calculated
the estimated annual percent change in disparities for each time period using log
normal linear regression modeling. RESULTS: Black-White disparity increased from
1984 to 1990, followed by a large increase from 1991 to 1996, and a smaller
increase from 1997 to 2001. Black-White disparity moderated from 2002 to 2005 and
rose again from 2006 to 2013. Hispanic-White disparity increased from 1984 to
1997 but declined after 1998. Black-White and Hispanic-White disparities
increased for men who have sex with men during 2008 to 2013. CONCLUSIONS: Recent
increases in racial/ethnic disparities of AIDS diagnoses were observed and may be
due in part to care continuum inequalities. We suggest assessing disparities in
AIDS diagnoses as a high-level measure to capture changes at multiple stages of
the care continuum collectively. Future research should examine determinants of
racial/ethnic differences at each step of the continuum to better identify
characteristics driving disparities.
PMID- 28506567
TI - The impact of walk-in centres and GP co-operatives on emergency department
presentations: A systematic review of the literature.
AB - BACKGROUND: Internationally, non-urgent presentations are increasing the pressure
on Emergency Department (ED) staff and resources. This systematic review aims to
identify the impact of alternative emergency care pathways on ED presentations -
specifically GP cooperatives and walk-in clinics. METHODS: Based on a structured
PICO enquiry with either walk-in clinic or GP cooperative as the intervention, a
search was made for peer-reviewed publications in English, between 2000 and 2014.
Medline plus, OVID, PubMed, and Google Scholar were searched. The Critical
Appraisal Skills Program (CASP) guidelines were used to assess study quality and
data was extracted using an adapted JBI Qualitative Assessment and Review
Instrument (QARI). Subsequent reporting followed the PRISMA guideline. RESULTS:
Eleven high quality quantitative studies met the inclusion criteria. Walk-in
clinics do have the potential to reduce non-urgent emergency department
presentations, however evidence of this effect is low. GP cooperatives offer an
alternative care stream for patients presenting to the ED and do significantly
reduce local ED attendances. Community members need to be made aware of these
options in order to make informed treatment choices. CONCLUSION: GP cooperatives
in particular do have the potential to reduce ED workload. Further research is
required to uncover recent trends and patient outcomes for walk-in clinics and GP
cooperatives.
PMID- 28506568
TI - Adverse pathologic features in early oral squamous cell carcinoma and the role of
postoperative radiotherapy-a review.
AB - The use of postoperative radiotherapy (PORT) in early stage oral cancer with
adverse pathologic features (APFs) is controversial. Prognostically relevant APFs
reviewed were perineural invasion, lymphovascular invasion, depth of invasion,
worst pattern of invasion, and margin status. The current literature remains
divided with regard to the benefit of treatment escalation in these patients;
although these patients are at high risk for recurrence, the morbidity of PORT
needs to be balanced against the likely benefit in disease control. A wide
heterogeneity in the literature exists, likely as a result of differences in
treatment protocols. We performed a literature review of the role of PORT in
early-stage oral cancer with APFs. Based on the current evidence, the decision to
administer adjuvant therapy needs to be made on an individual basis; patients
with >1 APF are likely to benefit from PORT, and the use of risk-scoring systems
may help in decision making.
PMID- 28506569
TI - [Identifying potentially inappropriate prescriptions in patients over 65 years
old using original Beers criteria and their Spanish adaptation].
AB - OBJECTIVE: To compare the detection of potentially inappropriate medication (PIM)
using the original Beers criteria, a global reference for evaluating
prescriptions in the elderly, and their Spanish version. DESIGN: Retrospective
observational study LOCATION: A Primary Care area in the province of Murcia,
Spain. PARTICIPANTS: A total of 7,856 subjects aged 65 and over, with at least
one drug prescribed in a Primary Care Area of Spain during study period. METHOD:
Illnesses and treatments registered in the Primary Care computerised medical
history of patients were analysed during a 12month study period (2012). The
original Beers criteria and their Spanish adaptation were used to evaluate PIM,
considering both sets of criteria overall, and individually. RESULTS: The median
age of the patients was 76.0years, with the majority females (56.6%). Patients
received a median of 13 active substances and 66 medical prescriptions. The
percentage of patients prescribed PIM ranged from 44.8% according to the original
Beers criteria to 49.4% with the Spanish adaptation. CONCLUSIONS: PIMs are
frequent in our context. The original Beers criteria, if not adapted to the local
drug catalogue, underestimated the frequency of PIM in the elderly population
studied.
PMID- 28506570
TI - The local liver ablation with pulsed electric field stimulate systemic immune
reaction against hepatocellular carcinoma (HCC) with time-dependent cytokine
profile.
AB - AIM: How irreversible electroporation (IRE) affect immune status is still kept
unknown. This preclinical study is to investigate its local and systemic immune
reaction both on tumor-bearing and tumor free animals. METHODS: Liver ablation
was performed by a standard IRE instrument and proposal. Altogether 57 tumor
bearing mice and 10 tumor-free porcine livers were ablated. The reaction of
survival, radiology image, pathologically and immunologically were followed up.
The detailed cytokines and chemokines responses were recorded dynamically post
IRE ablation. RESULTS: IRE ablation induced coagulation and necrosis in liver. It
caused macrophages infiltration, in ablation zone. IRE ablation caused cellular
inflammation. It, corrected the abnormal drifted Th2 in HCC back to Th1 status,
promoting tumor eradication and host survival. The quantified cytokines and
chemokines indicate IRE can stimulate both local immune reaction and systemic
immune reaction. CONCLUSION: Local IRE ablation changes the abnormal drifted Th2
in HCC back to Th1 status, facilitating tumor eradication and host survival.
PMID- 28506571
TI - Tumor necrosis factor receptor-associated factor (TRAF) 6 inhibition mitigates
the pro-inflammatory roles and proliferation of rheumatoid arthritis fibroblast
like synoviocytes.
AB - BACKGROUND: Rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) play a
crucial role in RA through producing inflammatory cytokines and proteases which
could cause cartilage destruction. We showed previously that elevated expression
of tumor necrosis factor receptor-associated factor 6 (TRAF6) in RA synovium
correlated significantly with the severity of synovitis and the number of
infiltrated inflammatory cells. The aims of this study are to detect the roles of
TRAF6 in RA-FLSs. METHODS: Synovium were collected by closed needle biopsy from
inflamed knees of active RA patients, and FLSs were isolated by modified tissue
culture method. Expression of TRAF6 and CD55 in RA synivium was tested by double
immunofluorescence (IF) staining. TRAF6 in RA-FLSs was inhibited using Lentiviral
TRAF6-shRNA transfection. Real-time PCR and ELISA were used to detect the mRNA
expression and secretion of matrix metalloproteinase (MMP) and pro-inflammatory
cytokines. Cell Counting Kit-8 was used to detect cell proliferation, flow
cytometry was used to detect cell cycle, and Annexin V assay was used to detect
cell apoptosis. RESULTS: We showed that in the intimal and subintimal area of RA
synovium, TRAF6 was expressed obviously not only in CD55+ cells, but also in some
other CD55- cells. TRAF6 expression in RA-FLSs was suppressed effectively by
Lentiviral-TRAF6-shRNA transfection. Inhibition of TRAF6 in RA-FLSs mitigated the
mRNA levels and secretion of pro-inflammatory cytokines and MMPs, such as IL
1beta, IL-8, IL-6, TNF-alpha, MMP-13, and MMP-3. In addition, it decreased the
proliferation of RA-FLSs, blocked RA-FLSs in G0/G1-phase, and inhibited the cells
to go into S-phase and G2/M-phase, but not facilitated apoptosis of RA-FLSs.
CONCLUSION: TRAF6 plays direct roles in the pro-inflammatory effects and
proliferation of RA-FLSs. TRAF6 may serve as a potential treatment target in RA.
PMID- 28506572
TI - Inflammatory cytokines and oxidative stress biomarkers in irritable bowel
syndrome: Association with digestive symptoms and quality of life.
AB - A growing body of evidence suggests a possible role for low-grade inflammation in
the pathogenesis of irritable bowel syndrome (IBS). The objectives of this study
were to measure serum levels of tumor necrosis factor (TNF)-alpha, interleukin
(IL)-17, interleukin (IL)-10, malondialdehyde (MDA) and total antioxidant
capacity (TAC) in IBS patients and healthy controls (HCs), and to evaluate
possible correlations of such markers with gastrointestinal (GI) symptoms and
quality of life (QoL). Ninety Rome III positive IBS patients and 90 sex and age
matched HCs were recruited. GI symptoms, IBS-QoL, IBS severity score system
(IBSSS), and the serum levels of inflammatory cytokines and oxidative stress
biomarkers were evaluated. In IBS patients, TNFalpha, IL-17 and MDA cytokines
were significantly (P<0.05) higher, and IL-10 cytokine and TAC were significantly
(P<0.05) lower vs. HCs. When comparing IBS subtypes, TNFalpha and IL-17 were
significantly (P<0.05) higher, and IL-10 was significantly (P<0.05) lower in
diarrhea predominant IBS (IBS-D) compared to HCs, whereas the inflammatory
cytokine profile of other subtypes more closely resembled that of HCs. The serum
levels of MDA and TAC were significantly different (P<0.05) in all the subtypes
vs. HCs. All the inflammatory cytokines had significant (P<0.05) correlations
with GI symptoms, IBSSS and IBS-QoL, whereas no significant association was found
between oxidative stress biomarkers and these symptoms. IBS-D patients display
increased pro-inflammatory cytokines and decreased anti-inflammatory cytokines.
Present study demonstrated a correlation between inflammatory cytokines and both
IBS symptoms and QoL.
PMID- 28506573
TI - Nanogenerators for Human Body Energy Harvesting.
AB - Humans generate remarkable quantities of energy while performing daily
activities, but this energy usually dissipates into the environment. Here, we
address recent progress in the development of nanogenerators (NGs): devices that
are able to harvest such body-produced biomechanical and thermal energies by
exploiting piezoelectric, triboelectric, and thermoelectric physical effects. In
designing NGs, the end-user's comfort is a primary concern. Therefore, we focus
on recently developed materials giving flexibility and stretchability to NGs. In
addition, we summarize common fabrics for NG design. Finally, the mid-2020s
market forecasts for these promising technologies highlight the potential for the
commercialization of NGs because they may help contribute to the route of
innovation for developing self-powered systems.
PMID- 28506574
TI - The degree of integration of non-dispensing pharmacists in primary care practice
and the impact on health outcomes: A systematic review.
AB - BACKGROUND: A non-dispensing pharmacist conducts clinical pharmacy services aimed
at optimizing patients individual pharmacotherapy. Embedding a non-dispensing
pharmacist in primary care practice enables collaboration, probably enhancing
patient care. The degree of integration of non-dispensing pharmacists into
multidisciplinary health care teams varies strongly between settings. The degree
of integration may be a determinant for its success. OBJECTIVES: This study
investigates how the degree of integration of a non-dispensing pharmacist impacts
medication related health outcomes in primary care. METHODS: In this literature
review we searched two electronic databases and the reference list of published
literature reviews for studies about clinical pharmacy services performed by non
dispensing pharmacists physically co-located in primary care practice. We
assessed the degree of integration via key dimensions of integration based on the
conceptual framework of Walshe and Smith. We included English language studies of
any design that had a control group or baseline comparison published from 1966 to
June 2016. Descriptive statistics were used to correlate the degree of
integration to health outcomes. The analysis was stratified for disease-specific
and patient-centered clinical pharmacy services. RESULTS: Eighty-nine health
outcomes in 60 comparative studies contributed to the analysis. The accumulated
evidence from these studies shows no impact of the degree of integration of non
dispensing pharmacists on health outcomes. For disease specific clinical pharmacy
services the percentage of improved health outcomes for none, partial and fully
integrated NDPs is respectively 75%, 63% and 59%. For patient-centered clinical
pharmacy services the percentage of improved health outcomes for none, partial
and fully integrated NDPs is respectively 55%, 57% and 70%. CONCLUSIONS: Full
integration adds value to patient-centered clinical pharmacy services, but not to
disease-specific clinical pharmacy services. To obtain maximum benefits of
clinical pharmacy services for patients with multiple medications and
comorbidities, full integration of non-dispensing pharmacists should be promoted.
PMID- 28506575
TI - [Therapeutic education in primary cardiovascular prevention: 4 years sustained
interest].
AB - BACKGROUND: Our patient therapeutic education program yields improvements in
health after one year. But what can we see after 4 years, when the patient alone
is responsible for following the program? PATIENTS AND METHODS: Two hundred and
ninety-one patients participated in the first part of our study and were followed
during one year. Four years into the ongoing study, we reviewed the progress of
the first 200 patients. We compared the already published Risk Factors and Eating
Habits scores between the beginning of the study (T0), one year later (T1) and
after 4 years (T4). RESULTS: The Risk Factor score at T0 is 9.5+/-7.8, moving to
7+/-7.5 at T1, and then to 6.8+/-7.8 at T4 (P<0.001 between T0 and T1 and T0 and
T4). Endurance physical activities saw the greatest improvement: 0.79+/-5 at T0,
1.07+/-4.5 at T1 and -1.61+/-4.5 at T4 (P<0.001 between T0 and T1 and T0 and T4).
The Eating Habits score went from -18.2+/-7.3 to -22.2+/-6.4 and then to -23.5+/
6.4 (P<0.001 between T0 and T1 and T0 and T4). The best results were obtained
through increased consumption of whole grains, green vegetables and fish.
CONCLUSION: The positive results of the progress of risk factors and eating
habits, noted after one year, are even greater four years after the end of the
therapeutic education program.
PMID- 28506576
TI - [Clinical characteristics and follow-up of patients with magnetic resonance
imaging confirmed myopericarditis: A retrospective study].
AB - INTRODUCTION: Pericarditis are frequently associated with some degree of
concomitant myocardial involvement. Predominant pericarditis with limited
myocardial involvement are named myopericarditis. Data regarding myopericarditis
are scarce. PATIENTS AND METHODS: Retrospective chart review of all patients
admitted between 2002 and 2011 with magnetic resonance imaging confirmed
myopericarditis. RESULTS: Twenty-seven patients were included. Eighty-one percent
were men, with median age of 32 years. Infectious disease preceded
hospitalization in 55% of cases. Mean left ventricle ejection fraction at
admission was 55% with focal myocardial impairment mainly localized in lateral
and inferior walls. Coronary angiogram was performed in 37% of cases to rule out
an ischaemic aetiology. We identified 5 cases (19%) of myopericarditis preceded
by an episode of streptococcus group A throat infection. Non-sustained
ventricular tachycardia was observed in 15% of cases. After a 2-year follow-up
period, mortality rate was zero and recurrence rate was 15%. CONCLUSIONS: In our
series, myopericarditis was a benign disease affecting mostly young men, and
prognosis was good. A significant proportion of cases was preceded by group A
streptococcus infection.
PMID- 28506577
TI - [Oral anticoagulants adherence in elderly patients treated for atrial
fibrillation in the era of direct oral anticoagulants].
AB - BACKGROUND: The aim of this study was to determine the level of adherence to oral
anticoagulants in the population of elderly patients treated for a non-valvular
atrial fibrillation (AF) in the era of direct oral anticoagulants. PATIENTS AND
METHOD: This transversal study used Morisky scale to assess adherence to oral
anticoagulants. We also collected patients' reviews about the treatment and
factors explaining a poor adherence. RESULTS: Between January and June 2015, 64
patients were included in Loire Atlantique. Average age was 77.8 years, CHA2DS2
VASc score was 4.06 and treatment (vitamin K antagonists [VKAs] in 78% patients)
was prescribed since 4.3 years. According to Morisky scale, 84.4% of patients had
a good adherence. There was 88% of good adherence with AVK versus 71% with direct
oral anticoagulant, there was no statistically significant difference. The
prescriber and the knowledge of anticoagulant treatment role seemed to be
determinant factors. CONCLUSIONS: The level of adherence for oral anticoagulant
appears higher than in most published studies. Diversification of therapeutic
options could constitute an aid to personalize the prescription in order to
improve it.
PMID- 28506578
TI - [Congenital heart disease in adolescents and adults: Management in a general
cardiology department in Senegal].
AB - BACKGROUND: Congenital heart diseases in adults include malformations treated in
childhood that decompensate secondarily and those asymptomatic at birth, appear
later. This study aims to identify congenital heart diseases in adults in general
cardiology department of Senegal and to assess clinical presentations, treatment
and outcomes. METHODS: We conducted a cross-sectional and descriptive study based
on the records of patients aged at least 16 years and followed for congenital
heart disease in the cardiology department of the General Hospital of Grand-Yoff
in Dakar between May 2003 and March 2015. Diagnosis of heart disease was based on
echocardiography. RESULTS: We have registered 50 dossiers of patients equivalent
to a prevalence of 0.75%, with a female predominance (64%). The average age of
patients was 36.2+/-18.4 years (16-79 years), and mean age of diagnosis was
29.76+/-22.58 years. Dyspnea was the main sign (60%). Main malformations were the
atrial septal defect (38%), pulmonary stenosis (14%), the ventricular septal
defect (12%) and patent ductus arteriosus (10%). According to the classification
of Bethesda, heart disease was simple complexity (42%), intermediate (58%) or
severe (10%). The treatment was medical in 43 patients and 7 patients had
surgical repair. Main complications were infective endocarditis (10%), atrial
fibrillation (12%), heart failure (24%) and pulmonary arterial hypertension
(50%). CONCLUSION: Congenital heart diseases in adults seem underestimated in our
countries. Surgical repair is rare. It is necessary to ensure a good management
of the transition between pediatric and adult age.
PMID- 28506579
TI - [Initial management of ST-elevation myocardial infarction in 2014: From
guidelines to practices, survey of 176 French interventional cardiologists].
AB - BACKGROUND: Real life management of myocardial infarction has not recently been
evaluated in France. AIMS: To describe ST-elevation myocardial infarction
management in France in 2014 and to compare it with current guidelines. METHODS:
A multicentre study was performed. An e-mail questionnaire was sent to French
interventional cardiologists. Demographic data of interventional cardiologists,
procedural aspects of percutaneous coronary intervention, antithrombotic
treatments and patient rehabilitation have been investigated. RESULTS: One
hundred and seventy-six answers were analysed. Most of centres realized more than
600 annual angioplasties. An average of 209 myocardial infarctions were managed
per centre in 2014, more often in academic than in general or private centres
(respectively 51, 32 and 17% of infarctions). Anti-GPIIbIIIa (34% of the cases)
and thromboaspiration were not systematic but depend on patient's
characteristics, according to guidelines. Radial access was favoured in 85% of
the cases and increased for the last decade. Drug eluting stents were used in 62%
of cases. Unfractionated heparin and enoxaparine accounted for more than 80% of
anticoagulants treatments. Overall, use of clopidogrel was as high as that of
prasugrel or ticagrelor although clopidogrel is recommended in second-line.
Cardiovascular rehabilitation was proposed to more than 50% of patients.
CONCLUSION: In spite of heterogeneity of ST-elevation myocardial infarction
management in 2014, real-life practices generally comply with current guidelines.
PMID- 28506580
TI - [Hyponatremic-hypertensive syndrome successfully treated by endovascular therapy:
A case report].
AB - INTRODUCTION: Hyponatremic-hypertensive syndrome (HHS) is characterized by
hypertension and hyponatremia. CASE PRESENTATION: We report a case of HHS in a 73
year-old woman, revealed by a hyponatremia leading to status epilepticus, without
initial hypertension due to hypovolemia. She was successfully treated by
endovascular therapy without any long-term supplementation or anti-hypertensive
medication. CONCLUSION: Physiopathology hypothesis of HHS implicate pressure
natriuresis, in this case, hypertension is not initially found and we discuss
other hyponatremia mechanisms.
PMID- 28506581
TI - [Sudden death in Versailles: A review of a cardiovascular treatrise by Dionis
(1710)].
AB - In 1710, the surgeon Pierre Dionis publishes a Dissertation on sudden death.
Echoing and expanding the work of his Roman colleague Jean Marie Lancisi, he
describes and analyzes dozens of cases of sudden death observed by him. A large
number of cases was followed by autopsies allowing clinicopathological
confrontation. Are proposed causes of death (pulmonary embolism, myocardial
infarction, hemorrhagic stroke, arterial rupture, etc.), pathophysiological
mechanisms based on the ancient theory of humors, and preventive actions to avoid
these unexpected deaths. In this article, we oppose these old data to those of
current literature.
PMID- 28506582
TI - Dual functional small molecule fluorescent probes for image-guided estrogen
receptor-specific targeting coupled potent antiproliferative potency for breast
cancer therapy.
AB - A strategy by integrating biological imaging into early stages of the drug
discovery process can improve our understanding of drug activity during
preclinical and clinical study. In this article, we designed and synthesized
coumarin-based nonsteroidal type fluorescence ligands for drug-target binding
imaging. Among these synthesized compounds, 3e, 3f and 3h showed potent ER
binding affinity and 3e (IC50=0.012MUM) exhibited excellent ERalpha antagonistic
activity, its antiproliferative potency in breast cancer MCF-7 cells is
equipotent to the approved drug tamoxifen. The fluorescence of compounds 3e and
3f depended on the solvent properties and showed significant changes when mixed
with ERalpha or ERbeta in vitro. Furthermore, target molecule 3e could cross the
cell membrane, localize and image drug-target interaction in real time without
cell washing. Thus, the coumarin-based platform represents a promising new ER
targeted delivery vehicle with potential imaging and therapeutic properties.
PMID- 28506583
TI - Synthesis of enantiomerically enriched drug precursors and an insect pheromone
via reduction of ketones using commercially available carbonyl reductase
screening kit "Chiralscreen(r) OH".
AB - Commercially available "Chiralscreen(r) OH" starter kit containing five types of
carbonyl reductases (E001, E007, E031, E039, and E078) was used for the reduction
of several aromatic and aliphatic ketones to obtain enantiomerically enriched
drug precursors and an insect pheromone. Almost stereochemically pure secondary
alcohols, used in the synthesis of drugs such as (R)-rasagiline mesylate, (S)
rivastigmine, (R)-chlorphenesin carbamate, and (R)-mexiletine, and the insect
pheromone (4S,5R)-sitophilure, were conveniently obtained. The enzymes worked
well with ketones containing at least one non-bulky substituent at the carbonyl
group. The diverse stereochemical preference of the above five carbonyl
reductases was clarified.
PMID- 28506584
TI - Development of nonsteroidal glucocorticoid receptor modulators based on N-benzyl
N-(4-phenoxyphenyl)benzenesulfonamide scaffold.
AB - N-Benzyl-N-(4-phenoxyphenyl)benzenesulfonamide derivatives were developed as a
novel class of nonsteroidal glucocorticoid receptor (GR) modulators, which are
promising drug candidates for treating immune-related disorders. Focusing on the
similarity of the GR and progesterone receptor (PR) ligand-binding domain (LBD)
structures, we adopted our recently developed PR antagonist 10 as a lead compound
and synthesized a series of derivatives. We found that the N-(4
phenoxyphenyl)benzenesulfonamide skeleton serves as a versatile scaffold for GR
antagonists. Among them, 4-cyano derivative 14m was the most potent, with an IC50
value of 1.43MUM for GR. This compound showed good selectivity for GR; it
retained relatively weak antagonistic activity toward PR (IC50 for PR: 8.00MUM;
250-fold less potent than 10), but showed no activity toward AR, ERalpha or
ERbeta. Interestingly, the 4-amino derivative 15a exhibited transrepression
activity toward NF-kappaB in addition to GR-antagonistic activity, whereas 14m
did not. The structure-activity relationship for transrepression was different
from that for GR-antagonistic activity. Computational docking simulations
suggested that 15a might bind to the ligand-binding pocket of GR in a different
manner from 14m. These findings open up new possibilities for developing novel
nonsteroidal GR modulators with distinctive activity profiles.
PMID- 28506585
TI - C21-steroidal pregnane sapogenins and their derivatives as anti-inflammatory
agents.
AB - During the screening of natural anti-inflammatory agent, we identified some C21
steroidal pregnane sapogenins or the derivatives to inhibit TLR2, TLR3, and TLR4
initiatedinflammatory responses respectively. Treatment with active compounds 10,
2j and 3p failed to impact tumor necrosis factor-alpha (TNF-alpha) induced
nucleus translocation of NF-kappaB p65 subunit. However, these compounds
regulated distinct canonical or non-canonical NF-kappaB family members. Ectopic
expression of TNF receptor associated factor 6 (TRAF6) abrogated the inhibitory
activity of the compounds on production of pro-inflammatory cytokines downstream
of TLR4. These results suggested that compounds 10, 2j, and 3p suppressed TLR
initiated innate immunity through TRAF6 with differential regulation of NF-kappaB
family proteins.
PMID- 28506586
TI - Corrigendum to "Airborne Asbestos Exposures Associated with Gasket and Packing
Replacement: A Simulation Study of Flange and Valve Repair Work and an Assessment
of Exposure Variables" [Regul. Toxicol. Pharmacol. 71 (1) (2014) 35-51].
PMID- 28506587
TI - The Art of Feedback in Medical Practice.
PMID- 28506588
TI - Double-balloon enteroscopy: Indications, approaches, diagnostic and therapeutic
yield, and safety. Early experience at a single center.
AB - INTRODUCTION AND AIMS: Double-balloon enteroscopy has been improving the
visualization of the entire intestine for more than a decade. It is a
complementary method in the study of intestinal diseases that enables biopsies to
be taken and treatments to be administered. Our aim was to describe its main
indications, insertion routes, diagnostic/therapeutic yield, and complications.
MATERIALS AND METHODS: All patients referred to our unit with suspected small
bowel pathology were included. The insertion route (oral/anal) was determined
through diagnostic suspicion. The variables measured were: insertion route, small
bowel examination extent, endoscopic diagnosis/treatment, biopsy/histopathology
report, complications, and surgical findings. RESULTS: The study included 28
double-balloon enteroscopies performed on 23 patients, of which 10 were women and
13 were men (mean age of 52.95 years). The oral approach was the most widely used
(n=21), the main indication was overt small bowel bleeding (n=16), and the
general diagnostic yield was 65.21%. The therapeutic intervention rate was 39.1%
and the procedure was effective in all the cases. The most widely used treatment
was argon plasma therapy (n=7). The complication rate was 8.6%; one patient
presented with low blood pressure due to active bleeding and another had deep
mucosal laceration caused by the argon plasma. CONCLUSIONS: Double-balloon
enteroscopy is a safe and efficacious method for the study and management of
small bowel diseases, with an elevated diagnostic and therapeutic yield.
PMID- 28506589
TI - The relationship between dosimetric factors, side effects, and survival in
patients with non-small cell lung cancer treated with definitive radiotherapy.
AB - The patients with non-small cell lung cancer (NSCLC) treated with definitive
conformal radiotherapy (RT) were evaluated in terms of side effects and survival.
Normal tissue complication probability (NTCP) was calculated for 68 patients
treated between 2009 and 2012. Clinical and dosimetric factors were analyzed. The
median dose of 63 Gy (range: 54 to 70 Gy) was given with conformal RT with blocks
(n = 37), 3-dimensional conformal RT (3DCRT) (n = 11), or intensity-modulated RT
(IMRT) (n = 20). Acute grade 1 to 2 radiation pneumonitis (RP) was seen in 13% of
the patients. No significant relationship was found between RP and treatment and
dosimetric factors (p > 0.05). There was a positive correlation between median
"mean lung dose" (MLD) (17 Gy), lung V30 (20.5%), and NTCP (14%) (p < 0.001).
Median and 2-year overall survival (OS) and progression-free survival (PFS) were
27 and 18 months and 51% and 42%, respectively. In univariate analysis,
significant dose range for survival was found between 59.4 and 63 Gy (p < 0.01).
In multivariate analysis, response (p = 0.001), fraction dose of 1.8 Gy (p =
0.002), MLD <18 Gy (p = 0.04) for OS and response (p < 0.001), total dose > 59.4
Gy (p = 0.01), and tumor biologically effective dose (BED)3(Gy) <= 100.8 (p =
0.01) for PFS were found to be favorable factors. In our study, we found a linear
correlation between NTCP and MLD for RP risk estimation in patients with NSCLC.
Therapeutic dose range where MLD can be kept under 20 Gy with significant
survival benefit was found between 59.4 and 63 Gy. Increased therapeutic efficacy
will be possible using risk-adaptive RT techniques.
PMID- 28506590
TI - RNF213 p.R4810K Variant and Intracranial Arterial Stenosis or Occlusion in
Relatives of Patients with Moyamoya Disease.
AB - BACKGROUND: This study aimed to determine the effectiveness of genetic testing
for the p.R4810K variant (rs112735431) of the Mysterin/RNF213 gene, which is
associated with moyamoya disease and other intracranial vascular diseases, in the
family members of patients with moyamoya disease. METHODS: We performed
genotyping of the RNF213 p.R4810K polymorphism and magnetic resonance angiography
on 59 relatives of 18 index patients with moyamoya disease. Nineteen individuals
had follow-up magnetic resonance angiography with a mean follow-up period of 7.2
years. RESULTS: Six of the 34 individuals with the GA genotype (heterozygotes for
p.R4810K) showed intracranial steno-occlusive lesions in the magnetic resonance
angiography, whereas none of the 25 individuals with the GG genotype (wild type)
showed any abnormalities. Follow-up magnetic resonance angiography revealed de
novo lesions in 2 and disease progression in 1 of the 11 individuals with the GA
genotype, despite none of the 8 individuals with the GG genotype showing any
changes. Accordingly, 8 individuals had steno-occlusive lesions at the last
follow-up, and all had the p.R4810K risk variant. The prevalence of steno
occlusive intracranial arterial diseases in family members with the p.R4810K
variant was 23.5% (95% confidence interval: 9.27%-37.78%), which was
significantly higher than in those without the variant (0%, P = .0160).
CONCLUSIONS: Genotyping of the p.R4810K missense variant is useful for
identifying individuals with an elevated risk for steno-occlusive intracranial
arterial diseases in the family members of patients with moyamoya disease.
PMID- 28506591
TI - Early Echocardiography Has a Low Yield in Patients with Transient Ischemic
Attack.
AB - STUDY OBJECTIVE: Current guidelines recommend patients presenting with transient
ischemic attack (TIA) undergo echocardiography to evaluate for a cardiac source.
However, echocardiography is not available daily at many centers. We assessed the
yield from early transthoracic echocardiography (TTE) in consecutive patients
with TIA evaluated in an emergency department observation unit (EDOU) protocol.
METHODS: This observational cohort study took place in an academic medical center
from January 1, 2011 to July 31, 2013. Patients seen in the emergency department,
assigned to the EDOU for a TIA accelerated diagnostic protocol and discharged
with a diagnosis of TIA were included. We retrospectively collected baseline
patient characteristics, ABCD2 score, neuroimaging, telemetry, TTE, and 3-month
clinical outcomes. RESULTS: Of 236 subjects (mean age 62 +/- 15 years, 68%
female, 57% African American, 17% with history of stroke, 27% with history of
cardiac disease, mean ABCD2 score 3.8 +/- 1.5, mean EDOU length of stay 18.6 +/-
6.2 hours), abnormal bedside cardiac examination was identified in 19 (8%)
patients, abnormal electrocardiogram (ECG)/telemetry in 41 (17%), and abnormal
TTE in 64 (27%), 41 of which suggested a patent foramen ovale. Among 136 (58%)
patients with no previous cardiac disease or stroke, a normal bedside cardiac
examination, and normal ECG/telemetry, TTE identified no high-risk cardiac
causes. CONCLUSION: In patients with TIA presenting to an EDOU with no previous
cardiac disease or stroke, normal cardiac examination, and normal ECG/telemetry,
early TTE had a low yield for identifying high-risk cardiac causes. In EDOUs
where TTE is not available daily, outpatient TTE for this patient subgroup may be
considered to limit prolonged lengths of stay.
PMID- 28506592
TI - Trends in Long-Term Mortality and Morbidity in Patients with No Early
Complications after Stroke and Transient Ischemic Attack.
AB - BACKGROUND: Advances in acute management and secondary prevention have reduced
mortality and early recurrent risk after stroke and transient ischemic attack
(TIA). However, whether improved outcomes are sustained long term among those
without early adverse complications is not clear. We describe trends in long-term
mortality and morbidity in patients with ischemic stroke or TIA who are
clinically stable at 90 days. METHODS: This is a longitudinal cohort registry
study (2003-2013) of patients presenting to stroke centers in Ontario, Canada,
with a stroke or TIA, with no hospitalization, stroke, myocardial infarction
(MI), institutionalization, or death within 90 days (N = 26,698). Primary
outcomes were 1-, 3-, and 5-year age-adjusted composite rates of death, stroke or
MI, and institutionalization, and secondary analyses evaluated outcomes
individually. Trend tests were used to evaluate change over time. RESULTS: One
year adjusted composite rates decreased from 9.3% in 2003 to 7.4% in 2012 (trend
test P = .02). Significant decreases in 3-year (P < .001) and 5-year (P = .002)
composite rates were also observed. Rates of recurrent stroke decreased at 1 and
3 years (P < .01), but not 5 years (P = .21), whereas death rates declined across
follow-up times. Conversely, rates of institutionalization increased at 3 and 5
years (P < .01). CONCLUSIONS: Long-term mortality and morbidity post stroke and
TIA have declined, confirming trends for improved long-term outcomes for patients
clinically stable during the initial high-risk period. However, increased long
term rates of institutionalization also suggest that stroke and TIA patients are
at risk of long-term functional decline, despite improved clinical outcomes.
Further studies evaluating challenges for sustaining functional gains after
stroke and TIA are required.
PMID- 28506593
TI - A Rational Strategy for Reducing On-Target Off-Tumor Effects of CD38-Chimeric
Antigen Receptors by Affinity Optimization.
AB - Chimeric antigen receptors (CARs) can effectively redirect cytotoxic T cells
toward highly expressed surface antigens on tumor cells. The low expression of
several tumor-associated antigens (TAAs) on normal tissues, however, hinders
their safe targeting by CAR T cells due to on-target/off-tumor effects. Using the
multiple myeloma (MM)-associated CD38 antigen as a model system, here, we present
a rational approach for effective and tumor-selective targeting of such TAAs.
Using "light-chain exchange" technology, we combined the heavy chains of two high
affinity CD38 antibodies with 176 germline light chains and generated ~124 new
antibodies with 10- to >1,000-fold lower affinities to CD38. After categorizing
them into three distinct affinity classes, we incorporated the single-chain
variable fragments of eight antibodies from each class into new CARs. T cells
carrying these CD38-CARs were extensively evaluated for their on-tumor/off-tumor
cytotoxicity as well as CD38-dependent proliferation and cytokine production. We
identified CD38-CAR T cells of ~1,000- fold reduced affinity, which optimally
proliferated, produced Th1-like cytokines, and effectively lysed CD382+ MM cells,
but spared CD38+ healthy hematopoietic cells in vitro and in vivo. Thus, this
systematic approach is highly suitable for the generation of optimal CARs for
effective and selective targeting of TAAs.
PMID- 28506595
TI - Plumbagin suppresses the migration and invasion of glioma cells via
downregulation of MMP-2/9 expression and inaction of PI3K/Akt signaling pathway
in vitro.
AB - Plumbagin is a natural naphthoquinone constituent isolated from the roots of
medicinal plant Plumbago zeylanica L., and has demonstrated anti-proliferative
and anti-invasion activities in various cancer cells. However, its effect on the
migration and invasion of glioma cells has not been elucidated. Therefore, human
glioma U87 and U251 cells were treated with plumbagin at 1.0 and 2.0 MUM for 24
h, and cell migration and invasion were assessed with scratch wound healing and
invasion assays. The results showed that plumbagin significantly inhibited the
migration and invasion of U87 and U251 cells, suppressed the activity and
expression of MMP-2/-9, and inhibited the nuclear translocation of transcription
factors Sp1 in the U87 and U251 cells. Moreover, plumbagin reduced the level of p
PI3K and p-Akt in these cells. The combined treatment with plumbagin and PI3K/Akt
agonist insulin-like growth factor-1 (IGF-1) reversed plumbagin-mediated
inhibitory effects on MMP-2/-9 expression, cell migration and invasion. These
findings suggest that the plumbagin-induced inhibition of glioma cell migration
and invasion is closely associated with the downregulation of MMP-2/-9 expression
and activity, and suppression of PI3K/Akt signaling pathway activation. Thus,
plumbagin might be a potential anti-invasive agent in the treatment of glioma.
PMID- 28506594
TI - Fingolimod and Teriflunomide Attenuate Neurodegeneration in Mouse Models of
Neuronal Ceroid Lipofuscinosis.
AB - CLN diseases are rare lysosomal storage diseases characterized by progressive
axonal degeneration and neuron loss in the CNS, manifesting in disability,
blindness, and premature death. We have previously demonstrated that, in animal
models of infantile and juvenile forms of CLN disease (CLN1 and CLN3,
respectively), secondary neuroinflammation in the CNS substantially amplifies
neural damage, opening the possibility that immunomodulatory treatment might
improve disease outcome. First, we recapitulated the inflammatory phenotype,
originally seen in mice in autopsies of CLN patients. We then treated mouse
models of CLN1 and CLN3 disease with the clinically approved immunomodulatory
compounds fingolimod (0.5 mg/kg/day) and teriflunomide (10 mg/kg/day) by
consistent supply in the drinking water for 5 months. The treatment was well
tolerated and reduced T cell numbers and microgliosis in the CNS of both models.
Moreover, axonal damage, neuron loss, retinal thinning, and brain atrophy were
substantially attenuated in both models, along with reduced frequency of
myoclonic jerks in Ppt1-/- mice. Based on these findings, and because side
effects were not detected, we suggest that clinically approved immune modulators
such as fingolimod and teriflunomide may be suitable to attenuate progression of
CLN1 and CLN3 disease and, possibly, other orphan diseases with pathogenically
relevant neuroinflammation.
PMID- 28506597
TI - A practice pattern assessment of members of the Society of Pediatric Urology for
evaluation and treatment of urinary tract dilation.
AB - INTRODUCTION: Over the last decade the literature, including a multidisciplinary
consensus statement, has supported a paradigm shift in management of urinary
tract dilation, yet the impact on practice patterns has not been well documented.
OBJECTIVE: This study aims to elucidate specific practice patterns for treatment
of prenatal unilateral urinary tract dilation and to assess surgical intervention
patterns for ureteropelvic junction obstruction. STUDY DESIGN: An online survey
was distributed to 234 pediatric urologists through the Society of Pediatric
Urology. The survey was composed of five clinical case scenarios addressing
evaluation and management of unilateral urinary tract dilation. RESULTS: The
response rate was 71% (n = 168). Circumcision status, gender, and grade were
significant factors in recommending prophylactic antibiotics for newborn urinary
tract dilation. Prophylactic antibiotic use in the uncircumcised male and female
was twice that of a circumcised male for grade 3 (Table). This difference was
minimized for grade 4. Use of VCUG was high for circumcised males with grade 3 or
4 (Table). The choice of minimally invasive surgery for ureteropelvic junction
repair increased with age from 19% for a 5-month-old, 49% for a 2-year-old, and
85% for a 10-year-old. Notably, 44% of respondents would observe a 10-year-old
with intermittent obstruction. Retrograde pyelography was recommended in
conjunction with repair in 65% of respondents. Antegrade stent placement was the
most common choice (38-47%) for urinary diversion after pyeloplasty. Regarding
postoperative imaging, only 5% opted for routine renal scan whereas most would
perform renal ultrasound alone. DISCUSSION: Practice patterns seen for use of
prophylactic antibiotics are in agreement with the literature, which promotes
selective use in those at highest risk for urinary tract infections.
Interestingly, use of aggressive screening was not concordant with this
literature. Several studies have indicated an increased usage of robotic
pyeloplasty; however, results indicate that minimally invasive surgery is not
preferred in those younger than 6 months. Study limitations include use of
clinical case scenarios as opposed to actual clinical practice. CONCLUSION:
Practice patterns for prophylactic antibiotic use for neonatal urinary tract
dilation are dependent on gender, circumcision status, and grade. The use of
minimally invasive surgery for ureteropelvic junction repair increased with
patient age, with 50% preferring this modality at 2 years.
PMID- 28506598
TI - Long-term dynamics in a soft-bottom amphipod community and the influence of the
pelagic environment.
AB - The processes and patterns seen in coastal benthic communities can be strongly
influenced by the overlying pelagic environmental conditions. Integrating long
term biological and environmental data (both benthic and pelagic) can give
insight into the specific relationships between key benthic functional groups and
natural temporal changes in the marine environment. The identity and abundance of
amphipod species found at Station L4 (Western English Channel) were tracked for 7
years (2008-2014), whilst simultaneously, annual changes in phytoplankton
biomass, water temperature, salinity and chlorophyll a concentration were also
characterized. The main species were persistent and showed little variability
along the study period. Overall, however, there were significant changes in the
structure of the whole community between sampling times, highlighting the
importance of less numerically-dominant species in driving temporal variability.
Surprisingly, the current study did not detect a significant influence of the
phytoplankton biomass on benthic amphipod dynamics. On the other hand, there was
a clear and constant correlation between bottom water temperatures and amphipod
abundance. This pattern is different from that observed in other detritivorous
species at L4, highlighting the complexity of benthic-pelagic coupling and the
high variability of the response to pelagic conditions among different groups. As
a result of the biogeographic position of the Western English Channel, the key
role of amphipods in benthic communities, the influence of the temperature in
their populations dynamics, as well as the solid baseline provided here and in
previous studies, the monitoring of long-term amphipod dynamics in the English
Channel could be a valuable tool to evaluate the biological effect of climate
change over marine benthic communities.
PMID- 28506599
TI - Application of vadose-zone monitoring system for real-time characterization of
leachate percolation in and under a municipal landfill.
AB - Leachates from solid-waste landfills are considered a severe threat to
groundwater quality. The fate of pollutants in the waste and underlying
unsaturated zone is crucial for evaluating environmental risks and selecting a
restoration strategy. In this study, a vadose-zone monitoring system (VMS)
installed in a municipal landfill was used, for the first time, to continuously
track leachates percolation dynamics and assess their chemical transformation
across the entire thickness of the waste body (15m) and underlying unsaturated
zone (16m) to the water table. Winter rains were found to quickly infiltrate
through the waste and underlying vadose zone despite a clay cover that was
implemented as part of a restoration and leachate-prevention strategy. Within the
waste body, the flow pattern was controlled by preferential flow paths, which
changed frequently. It is hypothesized that ongoing decomposition of the waste
creates dynamic variations in the waste's physical structure and flow pattern.
Water samples collected from the waste layer indicated the formation of highly
polluted leachates. The chemical composition in the waste body showed extreme
variability between sampling points with respect to DOC (407-31,464mg/L), BOD/COD
ratios (0.07-0.55), Fe2+ (6.8-1154mg/L), ammonium (68-2924mg/L) and heavy metal
concentrations. Environmental hot spots creating concentrated, aggressive, "acid
phase" leachates still exist in the waste more than 13years after closing the
landfill. However, continuous changes in the flow pattern and moisture
distribution affected the creation and decay of such environments. In the
underlying sandy vadose zone, some sections repeatedly exhibited stronger and
faster flow characteristics than others. These local fluxes of concentrated
leachates rapidly transported heavy contaminant loads toward the groundwater.
However results showed evidence of continual attenuation processes in the deep
vadose zone, with the anaerobic digestion of organic matter, as well as the
significant retention of heavy metals.
PMID- 28506601
TI - A flatline Lead I in a neonate with suspected congenital heart disease.
AB - In a neonate with bradycardia and hypoxia, and clinical concern for critical
congenital heart disease (CCHD), highly unusual ECG findings were present. These
included a flatline Lead 1, and identical Leads 2, 3, and AVF. These
abnormalities were due to bilateral arm to leg lead exchanges and not to heart
disease. Complete cardiac workup including echocardiogram was normal.
PMID- 28506600
TI - Cardiac hemangioma caused ventricular arrhythmia: A rare case and literature
review.
AB - Cardiac hemangioma is a rare primary cardiac tumor. We reported the case of
patient with left ventricular hemangioma who was referred to our hospital
complaining of palpitation for one week. 24 h Holter revealed high episode of
ventricular arrhythmia. Echocardiography showed a mass at left ventricle, which
was also confirmed by MRI. The mass was successfully resected and postoperative
pathology confirmed cardiac capillary hemangioma. The patient recovered well with
no cardiac arrhythmia after surgery over 12 months of follow-up.
PMID- 28506596
TI - Advances in medical imaging for the diagnosis and management of common
genitourinary cancers.
AB - Medical imaging of the 3 most common genitourinary (GU) cancers-prostate
adenocarcinoma, renal cell carcinoma, and urothelial carcinoma of the bladder-has
evolved significantly during the last decades. The most commonly used imaging
modalities for the diagnosis, staging, and follow-up of GU cancers are computed
tomography, magnetic resonance imaging (MRI), and positron emission tomography
(PET). Multiplanar multidetector computed tomography and multiparametric MRI with
diffusion-weighted imaging are the main imaging modalities for renal cell
carcinoma and urothelial carcinoma, and although multiparametric MRI is rapidly
becoming the main imaging tool in the evaluation of prostate adenocarcinoma,
biopsy is still required for diagnosis. Functional and molecular imaging using 18
fluorodeoxyglucose-PET and sodium fluoride-PET are essential for the diagnosis,
and especially follow-up, of metastatic GU tumors. This review provides an
overview of the latest advances in the imaging of these 3 major GU cancers.
PMID- 28506602
TI - Ventricular tachycardia score - A novel method for wide QRS complex tachycardia
differentiation - Explained.
AB - Philosophy, merits and limitations of a novel method for wide QRS complex
tachycardia differentiation, based on a scoring system and called the ventricular
tachycardia (VT) score, were explained. The following criteria were assigned one
point: initial dominant R wave in V1; initial r>40 ms in V1 or V2; notched S in
V1; initial R wave in aVR; lead II RWPT>=50 ms; and absence of an RS in leads V1
V6. Atrioventricular dissociation (including fusion/capture beats and partial
dissociation) was assigned two points. We recommend >=3 VT score points for a
firm diagnosis of VT. A cut-off >=1 point can be used for diagnosis of VT when
highest overall accuracy rather than error-free diagnosis is desired. However, in
case of VT score of 0-2 (i.e., not fully diagnostic ECG), we recommend using
other options (electrophysiological study, clinical data, previous and following
ECGs, etc.) for confirming the diagnosis.
PMID- 28506603
TI - Exudative retinal detachment.
AB - Exudative retinal detachment develops when fluid collects in the subretinal
space. The subretinal space between the photoreceptors and the retinal pigment
epithelium is the remnant of the embryonic optic vesicle. In the developed eye
the subretinal space is of minimal size, but it can reopen under pathological
conditions that disrupt the integrity of blood-retinal barrier. Inflammatory,
infectious, infiltrative, neoplastic, vascular, and degenerative conditions may
be associated with blood-retinal barrier breakdown and the sequential development
of exudative retinal detachment. We elaborate on the pathogenesis and the
differential diagnosis of exudative retinal detachment and specifically discuss
the spectrum of diseases associated with exudative retinal detachment in uveitis
clinics.
PMID- 28506604
TI - The supraciliary space as a suitable pathway for glaucoma surgery: Ho-hum or home
run?
AB - The supraciliary space is a physiological route for aqueous humor outflow located
anteriorly between the outer surface of the ciliary body and the internal surface
of the sclera. Posteriorly, the suprachoroidal space is located between the
choroid and the internal surface of the sclera. These spaces have been targeted
as suitable and helpful pathways for glaucoma treatment, alternatives to the
traditional subconjunctival space. The subconjunctival surgical pathway is
affected by several limitations such as poor cosmesis, a lifetime risk for
endophthalmitis, and an unpredictable wound healing response. Because of these
limitations, the supraciliary space has gained growing interest as a possible
target for new glaucoma drainage devices such as: Gold Micro Shunt (SOLX Inc.;
Waltham, MA, USA), iStent Supra (Glaukos Corporation, Laguna Hills, CA, USA),
CyPass Micro-Stent (Transcend Medical Inc., Menlo Park, CA, USA), Aquashunt (OPKO
health Inc., Miami, FL, USA), STARflo (iSTAR Medical, Isnes, Belgium), and
Esnoper-Clip implant (AJL Ophthalmics, Alava, Spain). We review the current
literature concerning the supraciliary space to evaluate its safety and efficacy
as a suitable pathway for glaucoma surgical treatment.
PMID- 28506606
TI - Metabolic syndrome and in-hospital outcomes among pancreatic cancer patients.
AB - AIMS: Metabolic Syndrome (MetS) is an important etiologic and prognostic factor
for pancreatic cancer, but few studies have assessed health outcomes among
hospitalized pancreatic cancer patients. We examined the associations between
MetS and in-hospital outcomes, i.e. pancreatic resection, post-surgery
complications, in-hospital mortality and discharge disposition among hospitalized
patients with pancreatic cancer. METHODS: Using the Healthcare Cost and
Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) dataset from 2007 to
2011, we obtained data on 47,386 patients hospitalized with a primary diagnosis
of pancreatic cancer. Descriptive statistics and multivariable regression models
were used to compute estimates, odds ratios and 95% confidence intervals
adjusting for age, race/ethnicity, and socioeconomic status. RESULTS: Pancreatic
cancer patients with MetS were more likely to undergo pancreatic resection (OR:
1.14, 95% CI: 1.04-1.25) compared to those without MetS. However they were less
likely to experience post-surgical complications (OR: 0.90, 95% CI: 0.81-0.99),
discharge to a skilled nursing facility (OR: 0.90, 95% CI: 0.83-0.93), and less
likely to experience in-hospital mortality (OR: 0.52, 95% CI: 0.44-0.61) compared
to those without MetS. CONCLUSION: Hospitalized pancreatic cancer patients with a
clinical diagnosis of MetS were more likely to receive pancreatic resection, and
had reduced odds of post-surgical complications and in-hospital mortality. If
confirmed in future studies, then better understanding of the biological
mechanisms underlying this association will be needed, potentially leading to the
development of clinical and/or molecular biomarkers to improve early diagnosis of
pancreatic cancer and identify patients that may benefit from pancreatic
resection.
PMID- 28506607
TI - Corrigendum to "The role of Ntcp, Oatp2, Bsep and Mrp2 in liver injury induced by
Dioscorea bulbifera L. and Diosbulbin B in mice" [Environ. Toxicol. Pharmacol. 51
(2017) 16-22].
PMID- 28506605
TI - Post-Traumatic Stress Disorder among Older Adults Experiencing Motor Vehicle
Collision: A Multicenter Prospective Cohort Study.
AB - OBJECTIVE: To characterize risk factors for and consequences of post-traumatic
stress disorder (PTSD) among older adults evaluated in the emergency department
(ED) following motor vehicle collision (MVC). DESIGN: Prospective multicenter
longitudinal study (2011-2015). SETTING: 9 EDs across the United States.
PARTICIPANTS: Adults aged 65 years and older who presented to an ED after MVC
without severe injuries. MEASUREMENTS: PTSD symptoms were assessed 6 months after
the ED visit using the Impact of Event Scale-Revised. RESULTS: Of 223 patients,
clinically significant PTSD symptoms at 6 months were observed in 21% (95% CI 16%
26%). PTSD symptoms were more common in patients who did not have a college
degree, had depressive symptoms prior to the MVC, perceived the MVC as life
threatening, had severe ED pain, and expected their physical or emotional
recovery time to be greater than 30 days. Three factors (ED pain severity [0-10
scale], perceived life-threatening MVC [0-10 scale], and pre-MVC depressive
symptoms [yes to either of two questions]), predicted 6-month PTSD symptoms with
an area under the curve of 0.76. Compared to patients without PTSD symptoms,
those with PTSD symptoms were at higher risk for persistent pain (72% versus
30%), functional decline (67% versus 42%), and new disability (49% versus 18%).
CONCLUSIONS: Among older adults treated in the ED following MVC, clinically
significant PTSD symptoms at 6 months were present in 21% of patients and were
associated with adverse health outcomes. Increased risk for PTSD development can
be identified with moderate accuracy using information readily available in the
ED.
PMID- 28506608
TI - PLGA nanoparticles as chlorhexidine-delivery carrier to resin-dentin adhesive
interface.
AB - OBJECTIVE: To characterize and deliver fabricated CHX-loaded PLGA-nanoparticles
inside micron-sized dentinal-tubules of demineralized dentin-substrates and resin
dentin interface. METHODS: Nanoparticles fabricated by emulsion evaporation were
assessed in-vitro by different techniques. Delivery of drug-loaded nanoparticles
to demineralized dentin substrates, interaction with collagen matrix, and ex-vivo
CHX-release profiles using extracted teeth connected to experimental setup
simulating pulpal hydrostatic pressure were investigated. Furthermore,
nanoparticles association/interaction with a commercial dentin-adhesive applied
to demineralized dentin substrates were examined. RESULTS: The results showed
that the formulated nanoparticles demonstrated attractive physicochemical
properties, low cytotoxicity, potent antibacterial efficacy, and slow degradation
and gradual CHX release profiles. Nanoparticles delivered efficiently inside
dentinal-tubules structure to sufficient depth (>10MUm) against the simulated
upward pulpal hydrostatic-pressure, even after bonding-resins infiltration and
were attached/retained on collagen-fibrils. These results verified the potential
significance of this newly introduced drug-delivery therapeutic strategy for
future clinical applications and promote for a new era of future dental research.
SIGNIFICANCE: This innovative drug-delivery strategy has proven to be a reliable
method for delivering treatments that could be elaborated for other clinical
applications in adhesive and restorative dentistry.
PMID- 28506609
TI - Ageing kinetics and strength of airborne-particle abraded 3Y-TZP ceramics.
AB - OBJECTIVE: The combined effects of alumina airborne-particle abrasion and
prolonged in vitro ageing on the flexural strength of 3Y-TZP ceramic have been
studied. The aim was to identify the different effects on the surface and
subsurface regions that govern the performance of this popular bioceramic known
for its susceptibility to low-temperature degradation (LTD). METHODS: As-sintered
or airborne-particle abraded 3Y-TZP discs were subjected to ageing at 134 degrees
C for up to 480h. Biaxial flexural strength was measured and the relative amount
of monoclinic phase determined using X-ray diffraction. The transformed zone
depth (TZD) was observed on cross-sections with scanning electron microscopy
coupled with a focused ion beam. Segmented linear regression was used to analyze
the flexural strength and TZD as functions of the ageing time. RESULTS: A two
step linear ageing kinetics was detected in airborne-particle abraded specimens,
reflecting the different microstructures through which the LTD proceeds into the
bulk. A 10MUm thick altered zone under the abraded surface was involved in both
the surface strengthening and the increased ageing resistance. When the zone was
annihilated by the LTD, the strength of the ceramic specimens and the speed of
LTD returned to the values measured before abrasion. Even at prolonged ageing
times, the strength of abraded groups was not lower than that of as-sintered
groups. SIGNIFICANCE: Both the ageing kinetics and the flexural strength were
prominently affected by airborne-particle abrasion, which altered the subsurface
microstructure and phase composition. Airborne-particle abrasion was not harmful
to the 3Y-TZP ceramics' stability.
PMID- 28506610
TI - Decreased Serum Sirtuin-1 in COPD.
AB - BACKGROUND: The protein deacetylase sirtuin-1 (SIRT1) is an antiaging molecule
that is decreased in the lung in patients with COPD. Recently, SIRT1 was reported
to be detectable in serum, but serum SIRT1 (s120S) levels have not yet been
reported in patients with COPD. METHODS: Serum SIRT1 protein of all samples was
measured by Western blot, and the SIRT1 protein band densities were calculated
and compared with clinical parameters. RESULTS: Several molecular sizes of SIRT1,
including 120 kDa (actual size) and fragments (102 and 75 kDa) were quantified by
Western blot. Among them, only the 120-kDa s120S was significantly decreased in
patients with COPD compared with the control subjects without COPD (s120S ratio
in healthy subjects = 0.90 +/- 0.34 vs those with COPD = 0.68 +/- 0.24; P = .014)
and was positively correlated with airway obstruction (FEV1/FVC, r = 0.31; P =
.020); its severity measured by FEV1 % predicted (r = 0.29; P = .029). s120S also
showed a positive correlation with BMI (r = 0.36; P = .0077) and diffusing
capacity of the lung per unit volume (the carbon monoxide transfer coefficient:
KCO%) (r = 0.32; P = .025). It was also significantly decreased with increasing
severity of lung emphysema (r = -0.40; P = .027) and with a clinical history of
frequent COPD exacerbations (infrequent vs frequent, 0.76 +/- 0.20 vs 0.56 +/-
0.26; P = .027). SIRT1 was not detected in supernatant of A549 and primary
epithelial cells in normal culture conditions. CONCLUSIONS: s120S was decreased
in the patients with COPD, potentially as reflected by the reduced SIRT1 within
cells as a result of oxidative stress, and might be a potential biomarker for
certain disease characteristics of COPD.
PMID- 28506612
TI - Identification of Pulmonary Hypertension Caused by Left-Sided Heart Disease
(World Health Organization Group 2) Based on Cardiac Chamber Volumes Derived From
Chest CT Imaging.
AB - BACKGROUND: Evaluations of patients with pulmonary hypertension (PH) commonly
include chest CT imaging. We hypothesized that cardiac chamber volumes calculated
from the same CT scans can yield additional information to distinguish PH related
to left-sided heart disease (World Health Organization group 2) from other PH
subtypes. METHODS: Patients who had PH confirmed by right heart catheterization
and contrast-enhanced chest CT studies were enrolled in this retrospective
multicenter study. Cardiac chamber volumes were calculated using automated
segmentation software and compared between group 2 and non-group 2 patients with
PH. RESULTS: This study included 114 patients with PH, 27 (24%) of whom were
classified as group 2 based on their pulmonary capillary wedge pressure. Patients
with group 2 PH exhibited significantly larger median left atrial (LA) volumes
(118 mL vs 63 mL; P < .001), larger median left ventricular (LV) volumes (90 mL
vs 76 mL; P = .02), and smaller median right ventricular (RV) volumes (173 mL vs
210 mL; P = .005) than did non-group 2 patients. On multivariate analysis
adjusted for age, sex, and mean pulmonary arterial pressure, group 2 PH was
significantly associated with larger median LA and LV volumes (P < .001 and P =
.008, respectively) and decreased volume ratios of RA/LA, RV/LV, and RV/LA (P =
.001, P = .004, and P < .001, respectively). Enlarged LA volumes demonstrated a
high discriminatory ability for group 2 PH (area under the curve, 0.92; 95% CI,
0.870-0.968). CONCLUSIONS: Volumetric analysis of the cardiac chambers from
nongated chest CT scans, particularly with findings of an enlarged left atrium,
exhibited high discriminatory ability for identifying patients with PH due to
left-sided heart disease.
PMID- 28506613
TI - Effect of high pressure on the saccharification of starch in the tuberous root of
sweet potato (Ipomoea batatas).
AB - We analyzed the effect of high hydrostatic pressure (HHP) treatment on reducing
sugar production in the tuberous root of sweet potato (Ipomoea batatas), based on
pressure-gelatinization of starch and subsequent saccharification by internal
amylases. HHP treatment at up to 600MPa at ambient temperature for 10min did not
apparently affect the reducing sugar concentration in tuberous root. However, HHP
treatment at 100 to 500MPa and 60 degrees C or 70 degrees C for 10min increased
reducing sugar concentration as both the pressure and temperature increased. The
reducing sugar concentration after HHP treatment at 500MPa and 70 degrees C for
10min was roughly comparable to that of the thermal treatment control (80 degrees
C for 10min under atmospheric pressure). HHP treatment enabled the gelatinization
and enzymatic saccharification of starch in the tuberous root of sweet potato, at
a lower temperature than required by thermal treatment at atmospheric pressure.
PMID- 28506614
TI - Retrospective analysis of skin complications related to bone-anchored hearing aid
implant: association with surgical technique, quality of life, and audiological
benefit.
AB - INTRODUCTION: The bone-anchored hearing aid is an effective form of auditory
rehabilitation. Due to the nature of the implant, the most common complications
are skin related. A number of alternative surgical implantation techniques have
been used to reduce the frequency and severity of skin complications, including
the U-shaped graft and the linear incision. OBJECTIVE: To assess skin
complications and their association with surgical technique, quality of life, and
audiological benefit in patients with bone-anchored hearing aids. METHODS: This
was a retrospective study conducted in a tertiary referral center in Bogota,
Colombia. Patients who had been fitted with a bone-anchored hearing aid implant
(unilaterally or bilaterally) for at least 6 months were included in the study.
The Holgers classification was used to classify skin complications (Grade 0=none;
Grade 1=erythema; Grade 2=erythema and discharge; Grade 3=granulation tissue; and
Grade 4=inflammation/infection resulting in the removal of the abutment). The
Glasgow Benefit Inventory questionnaire was used to determine quality of life,
and the Abbreviated Profile of Hearing Aid Benefit questionnaire was used to
determine the subjective audiological benefit. RESULTS: A total of 37 patients
were included in the study (30 with unilateral implants and 7 with bilateral
implant). Of the 44 implants evaluated, 31 (70.3%) were associated with skin
complications (7 [15.9%] Grade 1; 4 [9.1%] Grade 2; 15 [34.1%] Grade 3, 5 [11.4%]
Grade 4). The U-shaped graft was statistically associated with major
complications (Grades 3 and 4) compared with the linear incision technique
(p=0.045). No statistically significant differences were found between
Abbreviated Profile of Hearing Aid Benefit scores and severity of complications.
Similarly, no differences were found between Glasgow Benefit Inventory physical
health questions and skin complications. CONCLUSION: Despite the high frequency,
skin complications did not seem to affect quality of life or subjective
audiological benefits of patients with bone-anchored hearing aids.
PMID- 28506611
TI - Clinical and Genetic Associations of Objectively Identified Interstitial Changes
in Smokers.
AB - BACKGROUND: Smoking-related lung injury may manifest on CT scans as both
emphysema and interstitial changes. We have developed an automated method to
quantify interstitial changes and hypothesized that this measurement would be
associated with lung function, quality of life, mortality, and a mucin 5B (MUC5B)
polymorphism. METHODS: Using CT scans from the Genetic Epidemiology of COPD
Study, we objectively labeled lung parenchyma as a tissue subtype. We calculated
the percentage of the lung occupied by interstitial subtypes. RESULTS: A total of
8,345 participants had clinical and CT scanning data available. A 5% absolute
increase in interstitial changes was associated with an absolute decrease in FVC
% predicted of 2.47% (P < .001) and a 1.36-point higher St. George's Respiratory
Questionnaire score (P < .001). Among the 6,827 participants with mortality data,
a 5% increase in interstitial changes was associated with a 29% increased risk of
death (P < .001). These associations were present in a subgroup without visually
defined interstitial lung abnormalities, as well as in those with normal
spirometric test results, and in those without chronic respiratory symptoms. In
non-Hispanic whites, for each copy of the minor allele of the MUC5B promoter
polymorphism, there was a 0.64% (P < .001) absolute increase in the percentage of
lung with interstitial changes. CONCLUSIONS: Objective interstitial changes on CT
scans were associated with impaired lung function, worse quality of life,
increased mortality, and more copies of a MUC5B promoter polymorphism, suggesting
that these changes may be a marker of susceptibility to smoking-related lung
injury, detectable even in those who are healthy by other measures.
PMID- 28506615
TI - Modelling asymmetric somitogenesis: Deciphering the mechanisms behind species
differences.
AB - Somitogenesis is one of the major hallmarks of bilateral symmetry in vertebrates.
This symmetry is lost when retinoic acid (RA) signalling is inhibited, allowing
the left-right determination pathway to influence somitogenesis. In all three
studied vertebrate model species, zebrafish, chicken and mouse, the frequency of
somite formation becomes asymmetric, with slower gene expression oscillations
driving somitogenesis on the right side. Still, intriguingly, the resulting left
right asymmetric phenotypes differ significantly between these model species.
While somitogenesis is generally considered as functionally equivalent among
different vertebrates, substantial differences exist in the subset of oscillating
genes between different vertebrate species. Variation also appears to exist in
the way oscillations cease and somite boundaries become patterned. In addition,
in absence of RA, the FGF8 gradient thought to constitute the determination
wavefront becomes asymmetric in zebrafish and mouse, extending more anteriorly to
the right, while remaining symmetric in chicken. Here we use a computational
modelling approach to decipher the causes underlying species differences in
asymmetric somitogenesis. Specifically, we investigate to what extent differences
can be explained from observed differences in FGF asymmetry and whether
differences in somite determination dynamics may also be involved. We demonstrate
that a simple clock-and-wavefront model incorporating the observed left-right
differences in somitogenesis frequency readily reproduces asymmetric
somitogenesis in chicken. However, incorporating asymmetry in FGF signalling was
insufficient to robustly reproduce mouse or zebrafish asymmetry phenotypes. In
order to explain these phenoptypes we needed to extend the basic model,
incorporating species-specific details of the somitogenesis determination
mechanism. Our results thus demonstrate that a combination of differences in FGF
dynamics and somite determination cause species differences in asymmetric
somitogenesis. In addition,they highlight the power of using computational models
as well as studying left-right asymmetry to obtain more insight in somitogenesis.
PMID- 28506616
TI - Outcomes of Hip Arthroscopy in Competitive Athletes.
AB - PURPOSE: To evaluate the minimum 2-year postoperative clinical outcomes and the
rate of return to sports in athletes who underwent capsular plication for the
treatment of ligamentous laxity and/or borderline dysplasia during hip
arthroscopy for the treatment of femoroacetabular impingement and labral
pathology. METHODS: Since 2008, data were prospectively collected on patients who
underwent hip arthroscopy for the treatment of femoroacetabular impingement
and/or labral tears. Inclusion criteria were as follows: athlete at the high
school, collegiate, or professional levels preoperatively, underwent capsular
plication, and preoperatively recorded patient-reported outcome scores including
modified Harris hip score (mHHS), nonarthritic athletic hip score (NAHS), hip
outcome score-sports-specific subscale (HOS-SSS), and visual analog scale (VAS).
Exclusion criteria were as follows: <16 years old, preoperative Tonnis grade >1,
and previous hip conditions. Sports activity and competitive levels were
collected at a minimum of 2 years postoperatively. RESULTS: Fifty-one hips (49
patients) met the inclusion criteria, and 41 hips (39 patients) had minimum 2
year follow-up (80.4% follow-up). Mean mHHS increased from 67.1 preoperatively to
83.5 (P < .0001). Mean NAHS increased from 66.8 to 88.8 (P < .0001). Mean HOS-SSS
improved from 46.8 to 80.1 (P < .0001). Mean VAS decreased from 5.1 to 1.7 (P <
.0001). Thirty-five (85.4%) hip arthroscopies allowed the patients to return to
sports at follow-up. Thirty-four (82.9%) hip arthroscopies allowed the patients
to maintain their competitive physical abilities at follow-up. CONCLUSIONS:
Patient-reported outcomes and VAS in athletes significantly improved at a minimum
of 2 years after capsular plication as a part of hip arthroscopy addressing
varying pathologies. In addition, most patients returned to sports at similar or
higher competitive levels. These results suggest that capsular plication is a
favorable treatment option in athletes with ligamentous laxity and/or borderline
dysplasia. LEVEL OF EVIDENCE: Level IV, therapeutic case series.
PMID- 28506617
TI - Arthroscopic Treatment of Hip Pain in Adolescent Patients With Borderline
Dysplasia of the Hip: Minimum 2-Year Follow-Up.
AB - PURPOSE: To examine arthroscopic treatment of hip pain in patients with
borderline hip dysplasia (lateral center edge angle [LCEA] between 20 degrees
and 25 degrees ). METHODS: From 2008 to 2013, patients below 18 years of age who
underwent arthroscopic hip surgery with an LCEA between 20 degrees and 25
degrees were retrospectively matched 1:1 to a control group without dysplasia
(LCEA >=25 degrees ) based on age, gender, femoroplasty, labral treatment, and
capsular plication. Indications for surgery included failure to improve with
nonoperative treatments and anti-inflammatory medications after 3 months. Patient
reported outcome data were collected using modified Harris hip score, hip outcome
score-activities of daily living subscale, hip outcome score-sports-specific
subscale, nonarthritic athletic hip score, and visual analog scale. RESULTS: From
2008 to 2013, 168 patients below the age of 18 underwent arthroscopic hip
surgery. Twenty-one patients met inclusion criteria and were matched 1:1 to a
control group. Follow-up was achieved for 17 patients in both groups (81%). Mean
follow-up time, age, and LCEA were 2.19 years, 15.5 years, and 22.3 degrees for
the dysplastic group and 2.16 years, 16.0 years, and 31.2 degrees for the
control group, respectively. Preoperative patient-reported outcomes between
groups were not statistically different. At the latest follow-up, both groups
showed statistically significant improvement over baseline in modified Harris hip
score, hip outcome score-activities of daily living subscale, hip outcome score
sports-specific subscale, nonarthritic athletic hip score, and visual analog
scale (P < .001). Latest follow-up scores were not statistically different
between groups. CONCLUSIONS: This study shows favorable 2-year outcomes in
adolescent patients with borderline dysplasia undergoing labral treatment and
capsular plication. Outcomes in the borderline dysplastic patients were as good
as those of a control group. Although adolescents with borderline dysplasia have
traditionally been a challenging group of patients to treat, these results
suggest that an arthroscopic approach that addresses both labral pathology and
instability may be beneficial. LEVEL OF EVIDENCE: Level IV, therapeutic case
series.
PMID- 28506618
TI - The PTZ kindling mouse model of epilepsy exhibits exploratory drive deficits and
aberrant activity amongst VTA dopamine neurons in both familiar and novel space.
AB - Recurrent seizures that define epilepsy are often accompanied by psychosocial
problems and cognitive deficits with incompletely understood aetiology. We
therefore used the pentylenetetrazol (PTZ) kindling model of epilepsy in mice to
examine potential seizure-associated neuropathologies, focusing on motivation,
memory and novel-environment-induced activation of midbrain dopaminergic neurons.
In addition to recurrent seizures, we found that PTZ kindling led to a strong
suppression of novelty-driven exploration while largely sparing fear-driven
exploration. The deficits in exploratory drive may be relevant for other
cognitive impairments since reduced unassisted rearing in a learning arena
correlated with poorer spatial memory of object location. Using c-Fos
immunofluorescence as a marker of neuronal activity, we observed that dopamine
neurons within the ventral tegmental area (VTA) of PTZ kindled mice demonstrate
hyperactivity at baseline and hypoactivity in response to a novel environment
compared to saline-injected cagemate controls. These data extend previous
findings of PTZ kindling-mediated disruptions of hippocampal processes important
for novel environment recognition and learning by demonstrating PTZ kindling also
induces motivational deficits that are associated with reduced stimulus-evoked
activation of VTA dopamine neurons. More broadly, these data help understand the
aetiology of complex behavioural changes in the PTZ kindling model, and may
assist in the development of superior diagnoses and treatments for epilepsy.
PMID- 28506619
TI - Long-term reliability of the visual EEG Poffenberger paradigm.
AB - The Poffenberger paradigm is a simple perception task that is used to estimate
the speed of information transfer between the two hemispheres, the so-called
interhemispheric transfer time (IHTT). Although the original paradigm is a
behavioral task, it can be combined with electroencephalography (EEG) to assess
the underlying neurophysiological processes during task execution. While older
studies have supported the validity of both paradigms for investigating
interhemispheric interactions, their long-term reliability has not been assessed
systematically before. The present study aims to fill this gap by determining
both internal consistency and long-term test-retest reliability of IHTTs produced
by using the two different versions of the Poffenberger paradigm in a sample of
26 healthy subjects. The results show high reliability for the EEG Poffenberger
paradigm. In contrast, reliability measures for the behavioral Poffenberger
paradigm were low. Hence, our results indicate that electrophysiological measures
of interhemispheric transfer are more reliable than behavioral measures; the
later should be used with caution in research investigating inter-individual
differences of neurocognitive measures.
PMID- 28506620
TI - Bombesin administration impairs memory and does not reverse memory deficit caused
by sleep deprivation.
AB - Sleep deprivation impairs performance in emotional memory tasks, however this
effect on memory is not completely understood. Possible mechanisms may involve an
alteration in neurotransmission systems, as shown by the fact that many drugs
that modulate neural pathways can prevent memory impairment by sleep loss.
Gastrin releasing peptide (GRP) is a neuropeptide that emerged as a regulatory
molecule of emotional memory through the modulation of other neurotransmission
systems. Thus, the present study addressed the effect of intraperitoneal (IP)
administration of bombesin (BB) (2.5, 5.0 and 10.0MUg/kg), a GRP agonist, on the
performance of Wistar rats in a multiple trail inhibitory avoidance (MTIA) task,
after sleep deprivation, using the modified multiple platforms method (MMPM).
Sleep deprived animals exhibited acquisition and retention impairment that was
not prevented by BB injection. In addition, non-sleep deprived animals treated
with BB before and after the training session, but not before the test, have
shown a retention deficit. In summary, BB did not improve the memory impairment
by sleep loss and, under normal conditions, produced a memory consolidation
deficit.
PMID- 28506621
TI - ZENK expression following conspecific and heterospecific playback in the zebra
finch auditory forebrain.
AB - Zebra finches (Taeniopygia guttata) are sexually dimorphic songbirds, not only in
appearance but also in vocal production: while males produce both calls and
songs, females only produce calls. This dimorphism provides a means to contrast
the auditory perception of vocalizations produced by songbird species of varying
degrees of relatedness in a dimorphic species to that of a monomorphic species,
species in which both males and females produce calls and songs (e.g., black
capped chickadees, Poecile atricapillus). In the current study, we examined
neuronal expression after playback of acoustically similar hetero- and
conspecific calls produced by species of differing phylogenetic relatedness to
our subject species, zebra finch. We measured the immediate early gene (IEG) ZENK
in two auditory areas of the forebrain (caudomedial mesopallium, CMM, and
caudomedial nidopallium, NCM). We found no significant differences in ZENK
expression in either male or female zebra finches regardless of playback
condition. We also discuss comparisons between our results and the results of a
previous study conducted by Avey et al. [1] on black-capped chickadees that used
similar stimulus types. These results are consistent with the previous study
which also found no significant differences in expression following playback of
calls produced by various heterospecific species and conspecifics [1]. Our
results suggest that, similar to black-capped chickadees, IEG expression in zebra
finch CMM and NCM is tied to the acoustic similarity of vocalizations and not the
phylogenetic relatedness of the species producing the vocalizations.
PMID- 28506622
TI - Meta-analyses of RELN variants in neuropsychiatric disorders.
AB - Reelin is a critical extracellular matrix glycoprotein and implicated in
neurodevelopment and psychiatric disorders in animal model studies. The genetic
polymorphism of RELN has also been reported to be associated with several
psychiatric disorders, but the results remain controversial. Here, we conducted
meta-analyses of RELN gene SNPs and related neuropsychiatric disorders
(schizophrenia, autistic spectrum disorders, attention-deficit hyperactivity
disorder, Alzheimer's disease and bipolar disorders). A total of 12 SNPs
(rs736707, rs362691, rs607755, rs2229864, rs7341475, rs262355, rs362719,
rs11496125, g.-888G>C, rs2299356, rs528528, and rs4298437) in RELN gene were
included into meta-analyses. Subgroup analyses based on ethnicity were performed.
We found that RELN rs736707 was significantly related with psychiatric disorders
(schizophrenia, autism spectrum disorders and attention-deficit hyperactivity
disorder) in Asian group (C vs T, OR=1.26, 95% CI=1.13-1.41, P<0.01, FDR<0.01),
and rs7341475 was only significantly associated with reduced risk of
schizophrenia in Caucasian (A vs G, OR=0.88, 95% CI=0.82-0.95, P<0.01, FDR<0.01).
No association of other SNPs and psychiatric disorders is found. These findings
suggest a role of RELN SNPs in psychiatric diseases, and indicate that further
researches in populations with different genetic background and studies with
larger sample size are of great value.
PMID- 28506623
TI - MeCP2-deficient mice have reduced alpha4 and alpha6 nicotinic receptor mRNA and
altered behavioral response to nicotinic agonists.
PMID- 28506624
TI - Emerging Pathogenic Respiratory Mycoplasma hominis Infections in Lung Transplant
Patients: Time to Reassesses it's Role as a Pathogen?
PMID- 28506625
TI - Differences between GesEPOC and GOLD in 2017.
PMID- 28506626
TI - Major Changes in the Spanish COPD Guidelines (GesEPOC) 2017: Crossing Bridges.
PMID- 28506628
TI - Corrections.
PMID- 28506629
TI - Hippocampal information processing across sleep/wake cycles.
AB - According to a two-stage memory consolidation model, during waking theta states,
afferent activity from the neocortex to the hippocampus induces transient
synaptic modification in the hippocampus, where the information is deposited as a
labile form of memory trace. During subsequent sharp-wave ripples (SPW-Rs), the
newly acquired hippocampal information is transferred to the neocortex and stored
as a long-lasting memory trace. Consistent with this hypothesis, waking theta
states and SPW-Rs distinctly control information flow in the hippocampal
entorhinal loop. Although both waking theta states and rapid eye movement (REM)
sleep are characterized by prominent hippocampal theta oscillations, the two
brain states involve distinct temporal coordination and oscillatory coupling in
the hippocampal-entorhinal circuit. While distinct brain states have distinct
network dynamics, firing rates of individual neurons in the hippocampal
entorhinal circuitry follow lognormal-like distributions in all states. Firing
rates of the same neurons are positively correlated across brain states and
testing environments, suggesting that memory is allocated in preconfigured,
rather than tabula rasa-type, skewed neuronal networks. The fast-firing minority
and slow-firing majority neurons, which can support network stability and
flexibility, are under distinct homeostatic regulations that are initiated by
spindles and SPW-Rs during slow wave sleep and implemented during subsequent REM
sleep.
PMID- 28506627
TI - RXRB Is an MHC-Encoded Susceptibility Gene Associated with Anti-Topoisomerase I
Antibody-Positive Systemic Sclerosis.
AB - Systemic sclerosis is a systemic autoimmune and connective tissue disorder
associated with the human leukocyte antigen locus. However, the functional
relationship between human leukocyte antigen gene(s) and disease development
remains unknown. To elucidate major histocompatibility complex-linked systemic
sclerosis genetics, we performed genotyping of major histocompatibility complex
borne microsatellites and HLA-DPB1 alleles using DNA obtained from 318 anti
topoisomerase I antibody-positive patients and 561 healthy controls, all of
Japanese descent. Those results revealed two major histocompatibility complex
haplotypes associated with systemic sclerosis. Exome sequencing and targeted
analysis of these risk haplotypes identified rs17847931 in RXRB as a
susceptibility variant (P = 1.3 * 10-15; odds ratio [OR] = 9.4) with amino acid
substitution p.V95A on the risk haplotype harboring HLA-DPB1*13:01. No identical
variant in the other haplotype including DPB1*09:01 was observed, though that
haplotype also showed a significant association (P = 8.5 * 10-22; OR = 4.3) with
systemic sclerosis. Furthermore, the number of risk factors was shown to be a
predominant factor, as individuals with two factors had elevated risk (P = 6.7 *
10-13; OR = 30.2). We concluded that RXRB may be involved in antifibrotic
activity in skin and chromatin remodeling.
PMID- 28506630
TI - Cost-effective HIV-1 virological monitoring in resource-limited settings using a
modified commercially available qPCR RNA assay.
AB - Virological monitoring through plasma viral load (PVL) quantification is
essential for clinical management of HIV patients undergoing antiretroviral
treatment (ART), and for detecting treatment failure. Quantitative PCR (qPCR)
based tests are the gold standard for measuring PVL. Largely because of their
high cost, however, implementation of these tests in low- and middle-income
countries fails to cover the testing demand. In this study, we aimed at reducing
the running cost of the commercially available Abbott RealTimeTM HIV-1 assay by
minimizing the reagent consumption. To this end, a modified version of the assay
was obtained by reducing the assay's reagents volume to about a half, and
validated using a panel of 104 plasma samples. Compared to the standard version,
the modified Abbott assay allowed for a 50% reduction in running costs. At the
same time, it showed a 100% concordance in identifying samples with detectable
viral load, strong correlation (Pearson's r=0.983, P<0.0001), and a high
agreement between PVL values (mean percent difference between PVL values+/
standard deviation=0.76+/-3.18%). In detecting viral failure (PVL>1000copiesmL
1), the modified assay showed a sensitivity of 94.6%, a specificity of 93.8%, and
a negative and positive predictive values of 93.8% and 94.6%, respectively. The
modified assay therefore reliably quantifies PVL, predicts viral failure, and
allows for a ca. 50% reduction in the assay's running costs. It may thus be
implemented as an ART monitoring tool in resource-limited settings and for
research purposes.
PMID- 28506631
TI - Susceptibility of neuroblastoma cells to rabies virus may be affected by passage
number.
AB - Maintaining a healthy, continuous immortalized cell line is essential for rabies
laboratories that perform virus isolation assays and test for the presence of
viral neutralizing antibodies. Individuals who routinely work with rabies virus,
such as rabies laboratory employees, or those who may have a high potential for
exposure to rabies virus, including veterinarians, should be tested for the
presence of anti-rabies viral neutralizing antibodies (VNA) every 6-24 months,
depending on potential exposure level. The gold standard for serum neutralization
assays require the use of live rabies virus and cells that are sensitive to
rabies virus infection. Additionally, virus isolation assays are routinely
performed in rabies laboratories as a back-up for the direct fluorescent antibody
test (dFAT). Currently there are no guidelines or publications recommending the
use of low, intermediate, or high passage cell lines in rabies assays. In this
study, we compared the sensitivity of intermediate, high, and extremely high
passaged neuroblastomas to rabies virus using virus isolation, serum
neutralization, and real time RT-PCR techniques. Additionally, cells were
examined microscopically to determine changes in morphology and dissemination of
rabies virus antigen between intermediate, high, and extremely high passage
cells. No significant difference was found between cell passage numbers and viral
susceptibility between intermediate and high passaged cells. However, extremely
high passaged cells (>=1200 passages) were less susceptible to viral infection
and/or produced less virus following inoculation. As a result, rabies
laboratories that use viral isolation and serum neutralization assays should
regularly assess cell susceptibility to ensure the integrity and repeatability of
the test.
PMID- 28506632
TI - Evaluation of HBsAg and anti-HBc assays in saliva and dried blood spot samples
according HIV status.
AB - Influence of HIV status in HBV markers detection in saliva and dried blood spots
(DBS) was not well established. This study aims to evaluate the performance of
optimized commercial immunoassay for identifying HBsAg and anti-HBc in saliva and
DBS according HIV status. A sum of 535 individuals grouped as HIV+, HBV+,
HIV/HBV+ and HIV/HBV- were recruited where 347 and 188 were included for HBsAg
and anti-HBc evaluation, respectively. Serum, DBS collected in Whatman 903 paper
and saliva obtained using salivette device were analyzed using EIA. Increased
sample volume and ROC curve analysis for cut off determination were used for DBS
and saliva testing. HBsAg detection in saliva and DBS exhibited sensitivities of
80.9% and 85.6% and specificities of 86.8% and 96.3%. Sensitivity of anti-HBc in
saliva and DBS were 82.4% and 76.9% and specificities in saliva and DBS were
96.9% and 91.7%. Low sensitivities were observed for HBsAg (62%) and anti-HBc
(47%) detection in saliva of HIV/HBV+ individuals. OD values were also lower for
HBsAg detection in DBS and saliva of HIV/HBV+ individuals compared to their serum
samples. Statistical significance was found for sensitivities in HBsAg detection
between saliva and DBS demonstrating high sensitivity for DBS specimens. In
conclusion, HIV status or antiretroviral treatment appears to interfere in the
performance of HBsAg and anti-HBc detection in DBS and saliva samples using the
adapted commercial EIA.
PMID- 28506633
TI - [Anaerobiospirillum succiniciproducens and Desulfovibrio desulfuricans in 2 cases
of insidious bacteremia].
AB - Two cases of insidious bacteremia by uncommon curve and spiral-shaped, motile
anaerobic gram-negative rods are presented. Both of them were of an unclear
origin and occurred in immunosuppressed patients with simultaneous diseases. The
key tests for the identification of Anaerobiospirillum were its micromorphology,
a strictly anaerobic condition, negative catalase activity, the special-potency
disk profile, glucose fermentation, and beta-NAG production. Desulfovibrio
species was identified by all the above preliminary tests but with a different
disk profile, as well as for being asaccharolytic and desulfoviridin and H2S
producer. We here alert about the resistance or intermediate susceptibility of
Anaerobiospirillum succiniciproducens against antimicrobial agents, such as
metronidazole, one of the first-line drugs used for the treatment of anaerobic
gram-negative infections. Aminopenicillins with beta-lactamase-inhibitor
combinations and imipenem were active for this agent. Desulfovibrio desulfuricans
was beta-lactamase producer and resistant to cephalosporins, while metronidazole,
imipenem and levofloxacin were active. A reliable identification of these
microorganisms is important for establishing the best therapeutic scheme.
PMID- 28506634
TI - [Antimicrobial susceptibility of Helicobacter pylori strains isolated from
gastric lesions].
AB - Antimicrobial susceptibility was evaluated by two diffusion methods: E-test
strips to determine minimum inhibitory concentration (MIC) and disk diffusion for
amoxicillin, clarithromycin, metronidazole and ciprofloxacin in 30 Helicobacter
pylori strains isolated from gastric biopsies. No strains were resistant to
amoxicillin, 17% (5/30) were resistant to clarithromycin, 20% (6/30)
ciprofloxacin by both methods, and 37% (11/30) to metronidazole by the E-test.
Although the number of strains studied was reduced, there was a single mismatch
in interpreting susceptibility when both methods were compared; the same mismatch
was observed for metronidazole, being categorized as sensitive by the E-test and
as intermediate by disk diffusion. No association between the histological type
of lesion and the resistance pattern found could be determined.
PMID- 28506636
TI - Multiple DNA Interactions Contribute to the Initiation of Telomerase Elongation.
AB - Telomerase maintains telomere length and chromosome integrity by adding short
tandem repeats of single-stranded DNA to the 3' ends, via reverse transcription
of a defined template region of its RNA subunit. To further understand the
telomerase elongation mechanism, we studied the primer utilization and extension
activity of the telomerase from the budding yeast Naumovozyma castellii
(Saccharomyces castellii), which displays a processive nucleotide and repeat
addition polymerization. For the efficient initiation of canonical elongation,
telomerase required 4-nt primer 3' end complementarity to the template RNA. This
DNA-RNA hybrid formation was highly important for the stabilization of an
initiation-competent telomerase-DNA complex. Anchor site interactions with the
DNA provided additional stabilization to the complex. Our studies indicate three
additional separate interactions along the length of the DNA primer, each
providing different and distinct contributions to the initiation event. A
sequence-independent anchor site interaction acts immediately adjacent to the
base-pairing 3' end, indicating a protein anchor site positioned very close to
the catalytic site. Two additional anchor regions further 5' on the DNA provide
sequence-specific contributions to the initiation of elongation. Remarkably, a
non-telomeric sequence in the distal 25- to 32-nt region negatively influences
the initiation of telomerase elongation, suggesting an anchor site with a
regulatory role in the telomerase elongation decision.
PMID- 28506635
TI - CryoEM Structure of an Influenza Virus Receptor-Binding Site Antibody-Antigen
Interface.
AB - Structure-based vaccine design depends on extensive structural analyses of
antigen-antibody complexes.Single-particle electron cryomicroscopy (cryoEM) can
circumvent some of the problems of x-ray crystallography as a pipeline for
obtaining the required structures. We have examined the potential of single
particle cryoEM for determining the structure of influenza-virus hemagglutinin
(HA):single-chain variable-domain fragment complexes, by studying a complex we
failed to crystallize in pursuing an extended project on the human immune
response to influenza vaccines.The result shows that a combination of cryoEM and
molecular modeling can yield details of the antigen-antibody interface, although
small variation in the twist of the rod-likeHA trimer limited the overall
resolution to about 4.5A.Comparison of principal 3D classes suggests ways to
modify the HA trimer to overcome this limitation. A closely related antibody from
the same donor did yield crystals when bound with the same HA, giving us an
independent validation of the cryoEM results.The two structures also augment our
understanding of receptor-binding site recognition by antibodies that neutralize
a wide range of influenza-virus variants.
PMID- 28506637
TI - Thiamine and benfotiamine prevent stress-induced suppression of hippocampal
neurogenesis in mice exposed to predation without affecting brain thiamine
diphosphate levels.
AB - Thiamine is essential for normal brain function and its deficiency causes
metabolic impairment, specific lesions, oxidative damage and reduced adult
hippocampal neurogenesis (AHN). Thiamine precursors with increased
bioavailability, especially benfotiamine, exert neuroprotective effects not only
for thiamine deficiency (TD), but also in mouse models of neurodegeneration. As
it is known that AHN is impaired by stress in rodents, we exposed C57BL6/J mice
to predator stress for 5 consecutive nights and studied the proliferation (number
of Ki67-positive cells) and survival (number of BrdU-positive cells) of newborn
immature neurons in the subgranular zone of the dentate gyrus. In stressed mice,
the number of Ki67- and BrdU-positive cells was reduced compared to non-stressed
animals. This reduction was prevented when the mice were treated (200mg/kg/day in
drinking water for 20days) with thiamine or benfotiamine, that were recently
found to prevent stress-induced behavioral changes and glycogen synthase kinase
3beta (GSK-3beta) upregulation in the CNS. Moreover, we show that thiamine and
benfotiamine counteract stress-induced bodyweight loss and suppress stress
induced anxiety-like behavior. Both treatments induced a modest increase in the
brain content of free thiamine while the level of thiamine diphosphate (ThDP)
remained unchanged, suggesting that the beneficial effects observed are not
linked to the role of this coenzyme in energy metabolism. Predator stress
increased hippocampal protein carbonylation, an indicator of oxidative stress.
This effect was antagonized by both thiamine and benfotiamine. Moreover, using
cultured mouse neuroblastoma cells, we show that in particular benfotiamine
protects against paraquat-induced oxidative stress. We therefore hypothesize that
thiamine compounds may act by boosting anti-oxidant cellular defenses, by a
mechanism that still remains to be unveiled. Our study demonstrates, for the
first time, that thiamine and benfotiamine prevent stress-induced inhibition of
hippocampal neurogenesis and accompanying physiological changes. The present data
suggest that thiamine precursors with high bioavailability might be useful as a
complementary therapy in several neuropsychiatric disorders.
PMID- 28506638
TI - Ionic liquid-based reagents improve the stability of midterm fecal sample
storage.
AB - Fecal samples are widely used in metagenomic research, which aims to elucidate
the relationship between human health and the intestinal microbiota. However, the
best conditions for stable and reliable storage and transport of these samples at
room temperature are still unknown, and whether samples stored at room
temperature for several days will maintain their microbiota composition is still
unknown. Here, we established and tested a preservation method using reagents
containing imidazolium- or pyridinium-based ionic liquids. We stored human fecal
samples in these reagents for up to 7 days at different temperatures.
Subsequently, all samples were sequenced and compared with fresh samples and/or
samples treated under other conditions. The 16S rRNA sequencing results suggested
that ionic liquid-based reagents could stabilize the composition of the
microbiota in fecal samples during a 7-day storage period, particularly when
stored at room temperature. Thus, this method may have implications in the
storage of fecal samples for metagenomic research.
PMID- 28506639
TI - Increased C-reactive protein plasma levels are not involved in the onset of post
operative atrial fibrillation.
AB - BACKGROUND: Increased inflammation biomarkers plasma levels, including C-reactive
protein (CRP), have been associated with the initiation and perpetuation of
atrial fibrillation (AF). However, it is not known whether an increased CRP
plasma level, without concomitant inflammation, is sufficient to induce AF. We
investigated whether higher CRP plasma levels, determined by the presence of
+219G>A CRP gene polymorphism, is associated with an increased risk of post
operative AF. METHODS: One hundred and fifteen adult patients submitted to
elective coronary surgery were genotyped for the CRP +219G>A polymorphism. CRP
plasma levels were determined by enzyme-linked immunosorbent assay. RESULTS: CRP
plasma levels before surgery were higher in GG than in GA+AA patients (3.4+/-3.1
vs. 1.7+/-1.8, p<0.015). Thirteen percent of the patients presented post
operative AF. Despite the positive correlation between the polymorphism and CRP
levels, there was no significant difference in the occurrence of post-operative
AF between the different genotypes. CONCLUSIONS: These results suggest that
increased CRP plasma levels that are not associated with an inflammatory process
are not sufficient to trigger AF after cardiac surgery.
PMID- 28506640
TI - Diagnostic accuracy of the Embolic Risk French Calculator for symptomatic
embolism with infective endocarditis among Japanese population.
AB - BACKGROUND: Recently, the Embolic Risk French Calculator (ER-Calculator) was
designed to predict symptomatic embolism (SE) associated with infective
endocarditis (IE), but external validation has not been reported. This study
aimed to determine predictors of SE and the diagnostic accuracy of the ER
Calculator in left-sided active IE among a Japanese population. METHODS: This
retrospective cohort study included 166 consecutive patients with a definite
diagnosis of left-sided IE from 1994 to 2015 in our institution. SE during the
period after initiation of antibiotic therapy was defined as new SE and embolism
during the period before initiation of antibiotic therapy was defined as previous
embolism. The primary endpoint was new SE. RESULTS: The mean age of patients was
63+/-17 years. New SE occurred in 23 (14%) patients at a median of 6 days
(interquartile range: 2.5-12.5 days) after initiation of antibiotic therapy. The
cumulative incidence of new SE at 12 weeks was 18.2%. The 2-week probability by
the ER-Calculator as well as previously reported predictors, such as previous
embolism, vegetation length (>10mm), and their combination, were associated with
a high risk of new SE. By receiver operating characteristic analysis, the area
under the curve of the 2-week probability by the ER-Calculator for prediction of
new SE was 0.75 and the optimal cut-off value was 8%. A 2-week probability >8% by
the ER-Calculator was the most useful predictor of new SE (hazard ratio 3.63, 95%
confidence interval 1.50-8.37; p=0.006), which was more remarkable for fatal
embolic events (hazard ratio 13.9, 95% confidence interval 3.19-95.4; p=0.004).
CONCLUSIONS: The ER-Calculator is a useful predictor of new SE. Predictive
ability is more remarkable for critical embolic events.
PMID- 28506641
TI - Guiding multimodal registration with learned optimization updates.
AB - In this paper, we address the multimodal registration problem from a novel
perspective, aiming to predict the transformation aligning images directly from
their visual appearance. We formulate the prediction as a supervised regression
task, with joint image descriptors as input and the output are the parameters of
the transformation that guide the moving image towards alignment. We model the
joint local appearance with context aware descriptors that capture both local and
global cues simultaneously in the two modalities, while the regression function
is based on the gradient boosted trees method capable of handling the very large
contextual feature space. The good properties of our predictions allow us to
couple them with a simple gradient-based optimization for the final registration.
Our approach can be applied to any transformation parametrization as well as a
broad range of modality pairs. Our method learns the relationship between the
intensity distributions of a pair of modalities by using prior knowledge in the
form of a small training set of aligned image pairs (in the order of 1-5 in our
experiments). We demonstrate the flexibility and generality of our method by
evaluating its performance on a variety of multimodal imaging pairs obtained from
two publicly available datasets, RIRE (brain MR, CT and PET) and IXI (brain MR).
We also show results for the very challenging deformable registration of
Intravascular Ultrasound and Histology images. In these experiments, our approach
has a larger capture range when compared to other state-of-the-art methods, while
improving registration accuracy in complex cases.
PMID- 28506642
TI - No-waiting dentine self-etch concept-Merit or hype.
AB - OBJECTIVE: A recently-launched universal adhesive, G-Premio Bond, provides
clinicians with the alternative to use the self-etch technique for bonding to
dentine without waiting for the adhesive to interact with the bonding substrate
(no-waiting self-etch; Japanese brochure), or after leaving the adhesive
undisturbed for 10s (10-s self-etch; international brochure). The present study
was performed to examine in vitro performance of this new universal adhesive
bonded to human coronal dentine using the two alternative self-etch modes.
METHODS: One hundred and ten specimens were bonded using two self-etch
application modes and examined with or without thermomechanical cycling (10,000
thermal cycles and 240,000 mechanical cycles) to simulate one year of intraoral
functioning. The bonded specimens were sectioned for microtensile bond testing,
ultrastructural and nanoleakage examination using transmission electron
microscopy. Changes in the composition of mineralised dentine after adhesive
application were examined using Fourier transform infrared spectroscopy. RESULTS:
Both reduced application time and thermomechanical cycling resulted in
significantly lower bond strengths, thinner hybrid layers, and significantly more
extensive nanoleakage after thermomechanical cycling. Using the conventional 10-s
application time improved bonding performance when compared with the no-waiting
self-etch technique. Nevertheless, nanoleakage was generally extensive under all
testing parameters employed for examining the adhesive. CONCLUSION: Although
sufficient bond strength to dentine may be achieved using the present universal
adhesive in the no-waiting self-etch mode that does not require clinicians to
wait prior to polymerisation of the adhesive, this self-etch concept requires
further technological refinement before it can be recommended as a clinical
technique. CLINICAL SIGNIFICANCE: Although the surge for cutting application time
to increase user friendliness remains the most frequently sought conduit for
advancement of dentine bonding technology, the use of the present universal
adhesive in the no-waiting self-etch mode may not represent the best use of the
adhesive.
PMID- 28506643
TI - Epithelial basement membrane injury and regeneration modulates corneal fibrosis
after pseudomonas corneal ulcers in rabbits.
AB - The purpose of this study was to investigate whether myofibroblast-related
fibrosis (scarring) after microbial keratitis was modulated by the epithelial
basement membrane (EBM) injury and regeneration. Rabbits were infected with
Pseudomonas aeruginosa after epithelial scrape injury and the resultant severe
keratitis was treated with topical tobramycin. Corneas were analyzed from one to
four months after keratitis with slit lamp photos, immunohistochemistry for alpha
smooth muscle actin (alpha-SMA) and monocyte lineage marker CD11b, and
transmission electron microscopy. At one month after keratitis, corneas had no
detectible EBM lamina lucida or lamina densa, and the central stroma was packed
with myofibroblasts that in some eyes extended to the posterior corneal surface
with damage to Descemet's membrane and the endothelium. At one month, a nest of
stromal cells in the midst of the SMA + myofibroblasts in the stroma that were
CD11b+ may be fibrocyte precursors to myofibroblasts. At two to four months after
keratitis, the EBM fully-regenerated and myofibroblasts disappeared from the
anterior 60-90% of the stroma of all corneas, except for one four-month post
keratitis cornea where anterior myofibroblasts were still present in one
localized pocket in the cornea. The organization of the stromal extracellular
matrix also became less disorganized from two to four months after keratitis but
remained abnormal compared to controls at the last time point. Myofibroblasts
persisted in the posterior 10%-20% of posterior stroma even at four months after
keratitis in the central cornea where Descemet's membrane and the endothelium
were damaged. This study suggests that the EBM has a critical role in modulating
myofibroblast development and fibrosis after keratitis-similar to the role of EBM
in fibrosis after photorefractive keratectomy. Damage to EBM likely allows
epithelium-derived transforming growth factor beta (TGFbeta) to penetrate the
stroma and drive development and persistence of myofibroblasts. Eventual repair
of EBM leads to myofibroblast apoptosis when the cells are deprived of requisite
TGFbeta to maintain viability. The endothelium and Descemet's membrane may serve
a similar function modulating TGFbeta penetration into the posterior stroma-with
the source of TGFbeta likely being the aqueous humor.
PMID- 28506644
TI - Affinity purification of Car9-tagged proteins on silica matrices: Optimization of
a rapid and inexpensive protein purification technology.
AB - Car9, a dodecapeptide identified by cell surface display for its ability to bind
to the edge of carbonaceous materials, also binds to silica with high affinity.
The interaction can be disrupted with l-lysine or l-arginine, enabling a broad
range of technological applications. Previously, we reported that C-terminal Car9
extensions support efficient protein purification on underivatized silica. Here,
we show that the Car9 tag is functional and TEV protease-excisable when fused to
the N-termini of target proteins, and that it supports affinity purification
under denaturing conditions, albeit with reduced yields. We further demonstrate
that capture of Car9-tagged proteins is enhanced on small particle size silica
gels with large pores, that the concomitant problem of nonspecific protein
adsorption can be solved by lysing cells in the presence of 0.3% Tween 20, and
that efficient elution is achieved at reduced l-lysine concentrations under
alkaline conditions. An optimized small-scale purification kit incorporating the
above features allows Car9-tagged proteins to be inexpensively recovered in
minutes with better than 90% purity. The Car9 affinity purification technology
should prove valuable for laboratory-scale applications requiring rapid access to
milligram-quantities of proteins, and for preparative scale purification schemes
where cost and productivity are important factors.
PMID- 28506645
TI - Multiple roles of glyoxalase 1-mediated suppression of methylglyoxal glycation in
cancer biology-Involvement in tumour suppression, tumour growth, multidrug
resistance and target for chemotherapy.
AB - Glyoxalase 1 (Glo1) is part of the glyoxalase system in the cytoplasm of all
human cells. It catalyses the glutathione-dependent removal of the endogenous
reactive dicarbonyl metabolite, methylglyoxal (MG). MG is formed mainly as a side
product of anaerobic glycolysis. It modifies protein and DNA to form mainly
hydroimidazolone MG-H1 and imidazopurinone MGdG adducts, respectively. Abnormal
accumulation of MG, dicarbonyl stress, increases adduct levels which may induce
apoptosis and replication catastrophe. In the non-malignant state, Glo1 is a
tumour suppressor protein and small molecule inducers of Glo1 expression may find
use in cancer prevention. Increased Glo1 expression is permissive for growth of
tumours with high glycolytic activity and is thereby a biomarker of tumour
growth. High Glo1 expression is a cause of multi-drug resistance. It is produced
by over-activation of the Nrf2 pathway and GLO1 amplification. Glo1 inhibitors
are antitumour agents, inducing apoptosis and necrosis, and anoikis. Tumour stem
cells and tumours with high flux of MG formation and Glo1 expression are
sensitive to Glo1 inhibitor therapy. It is likely that MG-induced cell death
contributes to the mechanism of action of current antitumour agents. Common
refractory tumours have high prevalence of Glo1 overexpression for which Glo1
inhibitors may improve therapy.
PMID- 28506646
TI - Virtual Resting Pd/Pa From Coronary Angiography and Blood Flow Modelling:
Diagnostic Performance Against Fractional Flow Reserve.
AB - BACKGROUND: Fractional flow reserve (FFR) has been established as a useful
diagnostic tool. The distal coronary pressure to aortic pressure (Pd/Pa) ratio at
rest is a simpler physiologic index but also requires the use of the pressure
wire, whereas recently proposed virtual functional indices derived from coronary
imaging require complex blood flow modelling and/or are time-consuming. Our aim
was to test the diagnostic performance of virtual resting Pd/Pa using routine
angiographic images and a simple flow model. METHODS: Three-dimensional
quantitative coronary angiography (3D-QCA) was performed in 139 vessels (120
patients) with intermediate lesions assessed by FFR. The resting Pd/Pa for each
lesion was assessed by computational fluid dynamics. RESULTS: The discriminatory
power of virtual resting Pd/Pa against FFR (reference: <=0.80) was high (area
under the receiver operator characteristic curve [AUC]: 90.5% [95% CI: 85.4
95.6%]). Diagnostic accuracy, sensitivity and specificity for the optimal virtual
resting Pd/Pa cut-off (<=0.94) were 84.9%, 90.4% and 81.6%, respectively. Virtual
resting Pd/Pa demonstrated superior performance (p<0.001) versus 3D-QCA %area
stenosis (AUC: 77.5% [95% CI: 69.8-85.3%]). There was a good correlation between
virtual resting Pd/Pa and FFR (r=0.69, p<0.001). CONCLUSIONS: Virtual resting
Pd/Pa using routine angiographic data and a simple flow model provides fast
functional assessment of coronary lesions without requiring the pressure-wire and
hyperaemia induction. The high diagnostic performance of virtual resting Pd/Pa
for predicting FFR shows promise for using this simple/fast virtual index in
clinical practice.
PMID- 28506647
TI - Acute Structural Failure of the Trifecta Aortic Valve Bioprosthesis.
AB - Advancements in bioprosthetic valve technology have greatly enhanced the
haemodynamic performance and long-term durability of tissue valves. These
features, along with the key advantage of avoiding lifelong anticoagulation, have
made bioprosthetic valves increasingly attractive for clinicians and patients
alike. The St Jude Trifecta valve is a novel, bovine pericardial bioprosthesis
with promising early data for performance and safety. However, no prosthetic
valve is perfect and prosthesis failure can occur with even the most reliable and
well-designed devices. We report a case of early and acute structural
deterioration (stent-post leaflet rupture) of the Trifecta valve, explanted after
33 months, in a 76-year-old male.
PMID- 28506648
TI - Antegrade Versus Continuous Retrograde del Nido Cardioplegia in the David I
Operation.
AB - BACKGROUND: The efficacy of continuous retrograde del Nido cardioplegia for
myocardial protection is still controversial. We hypothesised that antegrade and
retrograde cardioplegia offer equivalent safety for myocardial protection in the
David I procedure. METHODS: We retrospectively reviewed 33 patients undergoing
the David I operation with antegrade or retrograde del Nido solution from June
2014 to January 2016. The outcomes were compared. The follow-up was 1 month to 15
months. RESULTS: There was no hospital mortality or reoperation in both groups.
Cardiopulmonary bypass, and aortic clamp times were similar. Troponin I level
(TnI), creatine kinase level (CKMB), left ventricular ejection fraction (LVEF),
ventilation times, intensive care unit (ICULOS) and hospital stay times (THLOS)
were similar between the two groups. The lactate level was slightly higher
(9.26+/-2.56 vs 7.17+/-1.58, p=0.01) in the antegrade group compared with the
retrograde group. The incidence of heart block was higher (four patients) in the
retrograde group (26.7% vs 0%, p=0.019). Only one patient (6.7%) required
implantation of a permanent cardiac pacemaker. CONCLUSION: Antegrade and
continuous retrograde del Nido cardioplegia can be used safely and effectively in
the David I operation. The continuous retrograde del Nido cardioplegia is
associated with a higher rate of temporary AV block which does not require
permanent pacing, and a lower lactate level.
PMID- 28506649
TI - Dose optimization in cardiac CT.
AB - Rapid progress in the field of Cardiac CT is fostered by the advances in CT
scanner technology as well as multiple clinical trials demonstrating its role in
coronary artery disease and other indications like congenital heart disease,
pulmonary vein assessment and pre transcatheter aortic valve replacement. The
cardiovascular imager today is responsible for delivering diagnostic image
quality while striking a balance with optimized radiation dose. Radiation dose is
the result of multiple scanner and patient related factors. Achieving a
justifiable radiation dose according to the ALARA principle requires an adept
understanding of the factors affecting radiation dose. We review different scan
factors and their effect on radiation dose and present strategies for radiation
dose optimization in cardiac CT.
PMID- 28506651
TI - A load-to-fracture and strain analysis of monolithic zirconia cantilevered
frameworks.
AB - STATEMENT OF PROBLEM: The dimensions of implant-supported fixed cantilevered
prostheses are important to prevent mechanical and biological complications.
Information on the optimum thickness and cantilever length for improving the
strength of zirconia cantilevered frameworks is limited in the literature.
PURPOSE: The purpose of this in vitro study was to investigate the effect of
cantilever length and occlusocervical thickness on the load-to-fracture and
strain distribution of zirconia frameworks. MATERIAL AND METHODS: Twenty-seven
rectangular prism-shaped specimens (6 mm thick buccolingually) were fabricated
using a computer-aided design and computer-aided manufacturing (CAD-CAM) milling
technique. The specimens were prepared in 9 groups (n=3) according to their
vertical dimensions (6*6 mm, 8*6 mm, and 10*6 mm) and cantilever loading distance
(7 mm, 10 mm, and 17 mm). All specimens were heat treated in a porcelain furnace
and thermocycled for 20000 cycles before the tests. Each framework was secured
using a clamp attached to the first 20 mm of the framework. A 3-dimensional image
correlation technique was used for a full-field measurement of strain during
testing. A load-to-fracture test was used until the specimens fractured. Maximum
force and principal strain data were analyzed by 2-way analysis of variance using
the maximum likelihood estimation method (alpha=.05). RESULTS: No statistically
significant effects (P>.05) were found for occlusocervical thickness and
cantilever length or between them on the strain distribution. The results showed
that the effect of occlusocervical thickness and cantilever length was
significant on the load to fracture (P<.001). No statistically significant
interaction was observed between the 2 factors (P>.05). CONCLUSIONS: Increased
occlusocervical thickness and decreased cantilever length allowed the cantilever
to withstand higher loads. The occlusocervical thicknesses and cantilever lengths
of zirconia frameworks tested withstood the maximum reported occlusal force. The
properties of components in the implant-abutment framework assembly should be
considered in the interpretation of these results.
PMID- 28506652
TI - Comparison of denture tooth movement between CAD-CAM and conventional fabrication
techniques.
AB - STATEMENT OF PROBLEM: Data comparing the denture tooth movement of computer-aided
design and computer-aided manufacturing (CAD-CAM) and conventional denture
processing techniques are lacking. PURPOSE: The purpose of this in vitro study
was to compare the denture tooth movement of pack-and-press, fluid resin,
injection, CAD-CAM-bonded, and CAD-CAM monolithic techniques for fabricating
dentures to determine which process produces the most accurate and reproducible
prosthesis. MATERIAL AND METHODS: A total of 50 dentures were evaluated, 10 for
each of the 5 groups. A master denture was fabricated and milled from
prepolymerized poly(methyl methacrylate). For the conventional processing
techniques (pack-and-press, fluid resin, and injection) a polyvinyl siloxane
putty mold of the master denture was made in which denture teeth were placed and
molten wax injected. The cameo surface of each wax-festooned denture was laser
scanned, resulting in a standard tessellation language (STL) format file. The CAD
CAM dentures included 2 subgroups: CAD-CAM-bonded teeth in which the denture
teeth were bonded into the milled denture base and CAD-CAM monolithic teeth in
which the denture teeth were milled as part of the denture base. After all
specimens had been fabricated, they were hydrated for 24 hours, and the cameo
surface laser scanned. The preprocessing and postprocessing scan files of each
denture were superimposed using surface-matching software. Measurements were made
at 64 locations, allowing evaluation of denture tooth movement in a buccal,
lingual, mesial-distal, and occlusal direction. The use of median and
interquartile range values was used to assess accuracy and reproducibility.
Levene and Kruskal-Wallis analyses of variance were used to evaluate differences
between processing techniques (alpha=.05). RESULTS: The CAD-CAM monolithic
technique was the most accurate, followed by fluid resin, CAD-CAM-bonded, pack
and-press, and injection. CAD-CAM monolithic technique was the most reproducible,
followed by pack-and-press, CAD-CAM-bonded, injection, and fluid resin.
Techniques involving compression during processing showed increased positive
occlusal tooth movement compared with techniques not involving compression.
CONCLUSIONS: CAD-CAM monolithic dentures produced the best combination of
accuracy and reproducibility of the tested techniques. The results from this
study demonstrate that varying amounts of tooth movement can be expected
depending on the processing technique. However, the clinical significance of
these differences is unknown.
PMID- 28506653
TI - Inhibition of denture plaque deposition on complete dentures by 2
methacryloyloxyethyl phosphorylcholine polymer coating: A clinical study.
AB - STATEMENT OF PROBLEM: Denture plaque-associated infections are regarded as a
source of serious dental and medical complications in the elderly population.
Methods of managing this problem are needed. PURPOSE: The purpose of this
clinical study was to evaluate the effects of treatment with a 2
methacryloyloxyethyl phosphorylcholine polymer, PMBPAz, on plaque deposition in
complete dentures. MATERIAL AND METHODS: The study protocol was approved by the
Ethics Committee of Showa University (#2013-013). Eleven individuals with
maxillary complete dentures participated in this study. Their dentures were
treated with PMBPAz, and the amount of denture plaque accumulation was evaluated
by staining the denture surfaces with methylene blue after 2 weeks of denture
usage. The same procedures were repeated to evaluate the original denture
surfaces as a control. The image of the stained denture surface was captured
using a digital camera, and the percentage of stained area, quantified as a pixel
based density, of the whole denture area (percentage of plaque index) was
calculated for the mucosal and polished surfaces. To quantify the biofilm on the
dentures, denture plaque biofilm was detached by ultrasonic vibration,
resuspended in diluent, and measured with a microplate reader at an optical
density of 620 nm. The effects of PMBPAz treatment on these variables were
statistically analyzed with ANOVA (alpha=.05). RESULTS: The mean +/-SD percentage
of plaque index was 40.7% +/-19.9% on the mucosal surfaces and 28.0% +/-16.8% on
the polished surfaces of the control denture. The mean percentage of plaque index
of PMBPAz-treated dentures significantly decreased to 17.4%% +/-12.0% on the
mucosal surfaces (P<.001) and 15.0% +/-9.9% on the polished surfaces (P<.05). The
quantification of plaque deposition agreed with the results of these image
analyses. CONCLUSIONS: These results demonstrated the effectiveness of the
treatment with the PMBPAz to inhibit the bacterial plaque deposition on complete
dentures.
PMID- 28506654
TI - Effect of number of firings on the color and translucency of ceramic core
materials with veneer ceramic of different thicknesses.
AB - STATEMENT OF PROBLEM: Whether masking or translucency should be the goal for
achieving an esthetic restoration with ceramic materials is unknown. PURPOSE: The
purpose of this in vitro study was to examine the effect of the number of firings
on the color and translucency of ceramic core material with different thicknesses
of veneer ceramic. MATERIAL AND METHODS: Three different ceramic systems were
used: IPS Empress (IE), IPS e.max Press (IEP), and Turkom Cera (TC). Ninety disk
shaped cores, 10 mm in diameter and 0.8 mm in thickness were prepared using each
system (n=30). The specimens were divided into 3 subgroups (n=10) according to
the thickness of the veneering ceramic: 0.5, 1.0, and 1.5 mm. The specimens were
fired 1, 3, and 5 times, and the color parameters of the specimens were measured.
The color measurements were repeated, and the data were statistically evaluated
using 2-way and multifactorial analysis of variance, the Duncan test, and the
Bonferroni post hoc test. RESULTS: The number of firings affected the
translucency parameter and CIELab values. Increased porcelain thickness led to
decreased translucency parameter and L* values and increased a* and b* values
(P<.05). The IE system was the most translucent (P<.001). The changes with
increased firing periods were not statistically significant (P>.05). The number
of firings affected the color change of the IE and IEP systems but not of the
translucency parameter system. CONCLUSIONS: Repeated firings and porcelain
thickness affected the final color and translucency of the ceramic systems
tested. These 2 factors adversely affected the esthetic result and should be
considered in both the preparation and the laboratory phase.
PMID- 28506655
TI - Fiber-reinforced composite fixed dental prostheses: A 4-year prospective clinical
trial evaluating survival, quality, and effects on surrounding periodontal
tissues.
AB - STATEMENT OF PROBLEM: Although fiber-reinforced composite fixed dental prostheses
(FRC FDPs) are a reliable treatment option for the restoration of single missing
teeth, comparatively few prospective clinical trials (PCT) exist. PURPOSE: The
purpose of this PCT was to evaluate the survival, quality outcome, and effect of
FRC FDPs on periodontal health over 4 years. MATERIAL AND METHODS: Twenty-six
consecutive patients (16 men, 10 women) receiving FRC FDPs with preimpregnated
unidirectional fiber reinforcement were included in the trial. Eighteen FRC FDPs
were placed in the maxilla and 8 in the mandible. Data from baseline, 12-, 36-,
and 48-months of follow-up were recorded, and the prostheses were classified as
"success," "survival," or "failure." Periodontal parameters (probing depth,
clinical attachment level, plaque index, and bleeding index were assessed, and
the quality was rated according to modified United States Public Health Service
(USPHS)/Ryge or World Dental Federation (FDI) criteria. RESULTS: Functional
survival at 4 years was 73.5% (95% confidence interval [CI], 52.9-87.3) with 17
FRC FDPs still functioning. Twelve of these were classified as "success" and 5 as
"survival." Overall survival was 53.0% (95% CI, 30.4-74.4). Six FRC FPDs failed
completely. Periodontal parameters did not change over the observation period.
Regression analysis showed that probing depth and clinical attachment level did
not influence the survival of FRC FDPs. According to USPHS/Ryge/FDI criteria only
"wear" and "surface luster" increased significantly over 4 years. CONCLUSIONS:
The survival rate of FRC FPDs confirms existing data. Negative effects on
periodontal health were not seen over the period of observation. Aging effects
such as wear were recorded and indicated that FRC FPDs are at risk of
disintegration, as they are composed of a fiber framework and veneering composite
resin.
PMID- 28506656
TI - Colorizing titanium-6aluminum-4vanadium alloy using electrochemical anodization:
Developing a color chart.
AB - Colorizing titanium alloys by electrochemical anodization is used in dentistry
especially for identification purposes. Colorization is the result of distinct
voltage applications to specific titanium alloys when placed in an electrolyte.
Titanium and titanium alloys differ in their ability to be anodized. As titanium
6aluminum-4vanadium is commonly used as an abutment material, we have developed a
specific color reference scale relating color to the voltage applied.
PMID- 28506658
TI - [Cognitive neuroscience of aging: explanatory models].
AB - The aim of the cognitive neuroscience of aging is the study of brain activity and
the cognitive processes associated with age. In order to understand the dynamics
of neurocognitive activity in older people, the present review highlights four
explanatory models. The first one (HAROLD) highlights brain bilaterality, mainly
in the pre-frontal cortex. The second paradigm (PASA) places special emphasis on
neuronal polarisation (anterior-posterior). The third model (CRUNCH) relates the
manifest activity of the brain to the level of complexity of the task. The last
one (ELSA) emphasises the spatial and temporal distribution of brain activity in
the different phases of recovery. Although different in their content, the four
explanatory models are perfectly compatible with the findings reported by
neuroimaging techniques, suggesting the use of compensation strategies and
cognitive reserve for interventions that may help to optimise the performance of
older people.
PMID- 28506659
TI - Comparison of density and output of sweat gland in tropical Africans and
temperate Koreans.
AB - Modification of sweating could be due to changes in activated sweat gland density
(ASGD) and/or activated sweat gland output (ASGO). The present study determined
regional and inter-ethnic differences in ASGD and ASGO during passive heating
between tropical natives (African, n=22) and temperate natives (Republic of
Korean, n=25). Heat load was carried out by immersing the half body into a hot
water bath for 30min. Tympanic temperature (Tty) and skin temperature (Ts) were
measured. Mean body temperature (mTb) was calculated. Sudomotor activities
including sweat onset time, sweat rate, ASGD, and ASGO were examined in eight
regions of the skin. Africans had smaller increase in mTb during passive heating
than Koreans. The onset time of sweating was much more delayed in Africans
compared to Koreans. In response to thermal load, ASGD and ASGO differed between
body regions in Africans and Koreans. In most skin regions, ASGD and ASGO were
lower in tropical Africans compared to those in temperate Koreans. Trunk portion
including chest, upper back, lower back, abdomen had greater swear rate, ASGD,
and ASGO compared to peripheral segments including upper arm, forearm, leg, and
thigh in both ethnic groups. Distribution patterns of ASGD over the body appeared
to be similar in both Africans and Koreans at the peak of thermal loading. In
conclusion, the present study demonstrates that sudomotor activity in tropical
Africans is reduced with lower ASGD and ASGO over the body surface compared to
temperate Koreans.
PMID- 28506657
TI - Understanding pre-mRNA splicing through crystallography.
AB - Crystallography is a powerful tool to determine the atomic structures of proteins
and RNAs. X-ray crystallography has been used to determine the structure of many
splicing related proteins and RNAs, making major contributions to our
understanding of the molecular mechanism and regulation of pre-mRNA splicing.
Compared to other structural methods, crystallography has its own advantage in
the high-resolution structural information it can provide and the unique
biological questions it can answer. In addition, two new crystallographic methods
- the serial femtosecond crystallography and 3D electron crystallography - were
developed to overcome some of the limitations of traditional X-ray
crystallography and broaden the range of biological problems that crystallography
can solve. This review discusses the theoretical basis, instrument requirements,
troubleshooting, and exciting potential of these crystallographic methods to
further our understanding of pre-mRNA splicing, a critical event in gene
expression of all eukaryotes.
PMID- 28506660
TI - Specific clones of Staphylococcus lugdunensis may be associated with colon
carcinoma.
AB - Staphylococcus lugdunensis produces a tannase with activity that may be
associated with the onset of colon carcinoma. To clarify this feature of colon
carcinoma-associated S. lugdunensis, we obtained isolates from healthy subjects
and patients with colon adenomas and carcinomas and analyzed their genetic
backgrounds. In total, 40 S. lugdunensis isolates from 288 rectal swabs collected
between 2002 and 2008 were used. These isolates were classified into four groups
according to the diseases of the subjects: healthy (n=13), colon carcinoma
(n=13), colon adenoma (n=9), and unknown (n=5). The isolates were also classified
by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing. In
addition, an antimicrobial susceptibility test and detection of resistance genes
were performed for all isolates. According to the PFGE analysis, 40 isolates
could be classified into five groups. Among the groups, carcinoma and colon
adenoma patients were significantly more frequently (40.9%) classified into group
D (p<0.05), whereas healthy subjects were more frequently (38.5%) classified into
group A. All isolates in group D were typed as ST27, which was clearly different
than isolates in the other groups. All isolates were susceptible to the
antimicrobial agents tested, including beta-lactams, although seven strains
produced beta-lactamase. Our data suggest that a specific clone of S. lugdunensis
might be associated with colon carcinoma and colon adenoma. This clone showed
high susceptibility to many antimicrobial agents. Therefore, eradication therapy
may lead to a decreased risk of colon carcinoma.
PMID- 28506661
TI - TRPA1 receptors in chronic cough.
PMID- 28506662
TI - Adiponectin down-regulates CREB and inhibits proliferation of A549 lung cancer
cells.
AB - INTRODUCTION: Adipokines are known to play a relevant role in a number of cancer
related molecular pathways. Adiponectin is a major adipokine with anti
inflammatory and beneficial metabolic actions. Furthermore, it has been shown to
exert anti-carcinogenic effects in various tumor models and some clinical studies
suggested an inverse relationship between circulating levels of adiponectin and
an increased risk for development of malignancies. On the other hand, the cyclic
AMP response element binding (CREB) transcription factor has been clearly linked
to lung cancer. METHODS: we analyzed cell proliferation, cell cycle of A549 cells
treated with adiponectin as well as CREB activation status in human lung
adenocarcinoma A549 cells and in non-small cell lung cancer (NSCLC) samples.
RESULTS: adiponectin treatment, at concentrations ranging between 5 and 50 MUg/ml
mimicking human serum levels, has a significant effect on reducing tumor cell
proliferation of A549 cells, mainly by altering cell cycle progression.
Importantly, we provide evidence that adiponectin clearly inhibits in a dose- and
time-dependent manner CREB phosphorylation (activation) and, at least in part,
also the level of CREB protein itself, preceding and accompanying the anti
proliferative effects in response to adiponectin. Moreover, in agreement with
previous studies demonstrating that CREB over-expression occurs in many tumors,
we also show by western-blotting from lung specimen that CREB is significantly up
regulated in NSCLC samples compared to adjacent normal tissues from six patients.
CONCLUSIONS: Overall, our results represent the first evidence of CREB inhibition
by adiponectin and may provide new insight into therapeutic strategies for lung
cancer.
PMID- 28506663
TI - Cough associated with gastro-oesophageal reflux disease (GORD): Japanese
experience.
AB - Differences in the aetiology as well as patient background of chronic cough have
been recognised among US, UK, and Japan. One of the marked differences has been
the prevalence of gastro-oesophageal reflux disease (GORD), which has been one of
the top three causes in Western countries. It was indeed uncommon or rare in
Japan, but, with the increasing prevalence of GOR itself, chronic cough
associated with GORD seems to have become more common. In this article, cough
associated with GORD will be reviewed based on literature and our Japanese
experience. Further, potentially broader relevance of GORD in chronic cough will
also be mentioned, highlighting the potential importance of dysmotiliy/non-acid
reflux.
PMID- 28506664
TI - Heliox delivered by high flow nasal cannula improves oxygenation in infants with
respiratory syncytial virus acute bronchiolitis.
AB - OBJECTIVE: The objective of this study is to evaluate the hypothesis that use of
heliox would result in improvement of gas exchange when used with high flow nasal
cannula in infants with RSV acute bronchiolitis. METHODS: All patients that met
the inclusion criteria were randomized to either heliox (70:30) or air-oxygen
mixture 30% via high flow nasal cannula at 8L/min for a continuous 24h.
Measurements were taken at baseline, after 2h, and at the end of the 24h.
RESULTS: This prospective study included 48 patients. After 2h of treatment with
heliox, the oxygen saturation and PaO2 significantly improved when compared with
the air-oxygen group, 98.3% vs. 92.9%, 62.0mmHg vs. 43.6mmHg (p=0.04 and 0.01),
respectively. Furthermore, PaO2/FiO2 ratio was significantly higher in the heliox
group when compared with the air-oxygen group, 206.7 vs. 145.3. Nevertheless, CO2
showed better elimination when heliox was used, without significance. MWCA score
dropped significantly in the heliox group, 2.2 points vs. 4.0 points in air
oxygen (p=0.04), 2h after starting the therapy. CONCLUSION: Transient improvement
of oxygenation in infants with RSV acute bronchiolitis during the initial phase
of the therapy is associated with heliox when provided with HFNC, may provide a
precious time for other therapeutic agents to work or for the disease to resolve
naturally, avoiding other aggressive interventions.
PMID- 28506665
TI - Motor development of preterm infants assessed by the Alberta Infant Motor Scale:
systematic review article.
AB - OBJECTIVE: Premature newborns are considered at risk for motor development
deficits, leading to the need for monitoring in early life. The aim of this study
was to systematically review the literature about gross motor development of
preterm infants, assessed by the Alberta Infant Motor Scale (AIMS) to identify
the main outcomes in development. DATA SOURCE: Systematic review of studies
published from 2006 to 2015, indexed in Pubmed, Scielo, Lilacs, and Medline
databases in English and Portuguese. The search strategy included the keywords:
Alberta Infant Motor Scale, prematurity, preterm, motor development, postural
control, and follow-up. DATA SUMMARY: A total of 101 articles were identified and
23 were selected, according to the inclusion criteria. The ages of the children
assessed in the studies varied, including the first 6 months up to 15 or 18
months of corrected age. The percentage variation in motor delay was identified
in the motor outcome descriptions of ten studies, ranging from 4% to 53%,
depending on the age when the infant was assessed. The studies show significant
differences in the motor development of preterm and full-term infants, with a
description of lower gross scores in the AIMS results of preterm infants.
CONCLUSIONS: It is essential that the follow-up services of at-risk infants have
assessment strategies and monitoring of gross motor development of preterm
infants; AIMS is an assessment tool indicated to identify atypical motor
development in this population.
PMID- 28506666
TI - Prevalence and factors associated with body mass index in children aged 9-11
years.
AB - OBJECTIVE: This study aimed to identify the prevalence and factors associated
with body mass index (BMI) in children aged 9-11 years. METHODS: The study is
part of the International Study of Childhood Obesity Lifestyle and the
Environment (ISCOLE). Body composition was determined using the bipolar
bioimpedance technique. The mean BMI value was categorized as recommended by the
World Health Organization. For seven consecutive days, participants used an
accelerometer to objectively monitor sedentary behavior (SB) and moderate to
vigorous physical activity. Individual factors (anthropometric and behavioral),
family aspects, and family and school environment were provided by participants
and parents and were analyzed by multilevel linear regression adjusted for
gender, ethnicity, school, number of siblings, and total annual family income.
RESULTS: The mean BMI was 20.1kg/m2, and 51.8% of the children were
overweight/obese (50.3% boys, 53.4% girls, p=0.014). Considering all
participants, the associated factors of BMI were body fat percentage (BF%,
beta=0.0216, p<0.001) and screen time (ST, beta=0.0050, p=0.006). In boys, the
associated factors were BF% (beta=0.0209, p<0.001), ST (beta=0.006, p=0.036), and
healthy eating policies or practices (beta=0.0276, p=0.025). In girls, only BF%
was associated (beta=0.0221, p<0.001) with BMI. CONCLUSIONS: High prevalence of
overweight/obesity was observed in children from Sao Caetano do Sul. Different
associated factors were identified between the genders, with only BF% being
common in both genders.
PMID- 28506667
TI - Is There an Upper Limit to Genome Size?
AB - At 50-fold the size of the human genome (3 Gb), the staggeringly huge genome of
147.3 Gb recently discovered in the fern Tmesipteris obliqua is comparable in
size to those of the other plant and animal record-holders (i.e., Paris japonica,
a flowering plant with a genome size of 148.8 Gb, and Protopterus aethiopicus, a
lungfish with a genome of 130 Gb). The synthesis of available information on
giant genomes suggests that the biological limit to genome size expansion in
eukaryotes may have been reached. We propose several explanations for why the
genomes of ferns, flowering plants, and lungfish, all of which have independently
undergone dramatic increases in genome size through a variety of mechanisms, do
not exceed 150 Gb.
PMID- 28506668
TI - Characterization of selected municipal solid waste components to estimate their
biodegradability.
AB - Biological treatments of Residual Municipal Solid Waste (RMSW) allow to divert
biodegradable materials from landfilling and recover valuable alternative
resources. The biodegradability of the waste components needs however to be
assessed in order to design the bioprocesses properly. The present study
investigated complementary approaches to aerobic and anaerobic biotests for a
more rapid evaluation. A representative sample of residual MSW was collected from
a Mechanical Biological Treatment (MBT) plant and sorted out into 13 fractions
according to the French standard procedure MODECOMTM. The different fractions
were analyzed for organic matter content, leaching behavior, contents in
biochemical constituents (determined by Van Soest's acid detergent fiber method),
Biochemical Oxygen Demand (BOD) and Bio-Methane Potential (BMP). Experimental
data were statistically treated by Principal Components Analysis (PCA).
Cumulative oxygen consumption from BOD tests and cumulative methane production
from BMP tests were found to be positively correlated in all waste fractions. No
correlation was observed between the results from BOD or BMP bioassays and the
contents in cellulose-like, hemicelluloses-like or labile organic compounds. No
correlation was observed either with the results from leaching tests (Soluble
COD). The contents in lignin-like compounds, evaluated as the non-extracted RES
fraction in Van Soest's method, was found however to impact negatively the
biodegradability assessed by BOD or BMP tests. Since cellulose, hemicelluloses
and lignin are the polymers responsible for the structuration of lignocellulosic
complexes, it was concluded that the structural organization of the organic
matter in the different waste fractions was more determinant on biodegradability
than the respective contents in individual biopolymers.
PMID- 28506669
TI - Recycling and characterization of carbon fibers from carbon fiber reinforced
epoxy matrix composites by a novel super-heated-steam method.
AB - In order to manufacture high quality recycled carbon fibers (R-CFs), carbon fiber
reinforced composite wastes were pyrolysed with super-heated steam at 550
degrees C in a fixed bed reactor for varying reaction times. The mechanical and
surface properties of the R-CFs were characterized with a single fiber tensile
test, interface shear strength (IFSS), scanning electron microscopy (SEM), and X
ray photoelectron spectroscopy (XPS). The surface analysis showed that there was
no matrix char residue on the fiber surfaces. The tensile strength and IFSS
values of the R-CFs were 90% and 115% compared to those of virgin carbon fibers
(V-CFs), respectively. The recycling efficiency of the R-CFs from the composites
were strongly dependent on the pyrolysis temperature, reaction time, and super
heated steam feeding rate.
PMID- 28506670
TI - Effect of simulated mechanical recycling processes on the structure and
properties of poly(lactic acid).
AB - The aim of this work is to study the effects of different simulated mechanical
recycling processes on the structure and properties of PLA. A commercial grade of
PLA was melt compounded and compression molded, then subjected to two different
recycling processes. The first recycling process consisted of an accelerated
ageing and a second melt processing step, while the other recycling process
included an accelerated ageing, a demanding washing process and a second melt
processing step. The intrinsic viscosity measurements indicate that both
recycling processes produce a degradation in PLA, which is more pronounced in the
sample subjected to the washing process. DSC results suggest an increase in the
mobility of the polymer chains in the recycled materials; however the degree of
crystallinity of PLA seems unchanged. The optical, mechanical and gas barrier
properties of PLA do not seem to be largely affected by the degradation suffered
during the different recycling processes. These results suggest that, despite the
degradation of PLA, the impact of the different simulated mechanical recycling
processes on the final properties is limited. Thus, the potential use of recycled
PLA in packaging applications is not jeopardized.
PMID- 28506671
TI - Modeling of flux, binding and substitution of urea molecules in the urea
transporter dvUT.
AB - Urea transporters (UTs) are transmembrane proteins that transport urea molecules
across cell membranes and play a crucial role in urea excretion and water
balance. Modeling the functional characteristics of UTs helps us understand how
their structures accomplish the functions at the atomic level, and facilitates
future therapeutic design targeting the UTs. This study was based on the crystal
structure of Desulfovibrio vulgaris urea transporter (dvUT). To model the binding
behavior of urea molecules in dvUT, we constructed a cooperative binding model.
To model the substitution of urea by the urea analogue N,N'-dimethylurea (DMU) in
dvUT, we calculated the occupation probability of DMU along the urea pore and the
ratio of the occupation probabilities of DMU at the external (Sext) and internal
(Sint) binding sites, and we established the mutual substitution rule for binding
and substitution of urea and DMU. Based on these calculations and modelings,
together with the use of the Monte Carlo (MC) method, we further modeled the urea
flux in dvUT, equilibrium urea binding to dvUT, and the substitution of urea by
DMU in the dvUT. Our modeling results are in good agreement with the existing
experimental functional data. Furthermore, the modelings have discovered the
microscopic process and mechanisms of those functional characteristics. The
methods and the results would help our future understanding of the underlying
mechanisms of the diseases associated with impaired UT functions and rational
drug design for the treatment of these diseases.
PMID- 28506672
TI - Comparison of the Nosocomial Pneumonia Mortality Prediction (NPMP) model with
standard mortality prediction tools.
AB - BACKGROUND: Severity or mortality prediction of nosocomial pneumonia could aid in
the effective triage of patients and assisting physicians. AIM: To compare
various severity assessment scoring systems for predicting intensive care unit
(ICU) mortality in nosocomial pneumonia patients. METHODS: A prospective cohort
study was conducted in a tertiary care university-affiliated hospital in Manipal,
India. One hundred patients with nosocomial pneumonia, admitted in the ICUs who
developed pneumonia after >48h of admission, were included. The Nosocomial
Pneumonia Mortality Prediction (NPMP) model, developed in our hospital, was
compared with Acute Physiology and Chronic Health Evaluation II (APACHE II),
Mortality Probability Model II (MPM72 II), Simplified Acute Physiology Score II
(SAPS II), Multiple Organ Dysfunction Score (MODS), Sequential Organ Failure
Assessment (SOFA), Clinical Pulmonary Infection Score (CPIS), Ventilator
Associated Pneumonia Predisposition, Insult, Response, Organ dysfunction (VAP
PIRO). Data and clinical variables were collected on the day of pneumonia
diagnosis. The outcome for the study was ICU mortality. The sensitivity and
specificity of the various scoring systems was analysed by plotting receiver
operating characteristic (ROC) curves and computing the area under the curve for
each of the mortality predicting tools. FINDINGS: NPMP, APACHE II, SAPS II, MPM72
II, SOFA, and VAP-PIRO were found to have similar and acceptable discrimination
power as assessed by the area under the ROC curve. The AUC values for the above
scores ranged from 0.735 to 0.762. CPIS and MODS showed least discrimination.
CONCLUSION: NPMP is a specific tool to predict mortality in nosocomial pneumonia
and is comparable to other standard scores.
PMID- 28506673
TI - High frequency of silver resistance genes in invasive isolates of Enterobacter
and Klebsiella species.
AB - BACKGROUND: Silver-based products have been marketed as an alternative to
antibiotics, and their consumption has increased. Bacteria may, however, develop
resistance to silver. AIM: To study the presence of genes encoding silver
resistance (silE, silP, silS) over time in three clinically important
Enterobacteriaceae genera. METHODS: Using polymerase chain reaction (PCR), 752
bloodstream isolates from the years 1990-2010 were investigated. Age, gender, and
ward of patients were registered, and the susceptibility to antibiotics and
silver nitrate was tested. Clonality and single nucleotide polymorphism were
assessed with repetitive element sequence-based PCR, multi-locus sequence typing,
and whole-genome sequencing. FINDINGS: Genes encoding silver resistance were
detected most frequently in Enterobacter spp. (48%), followed by Klebsiella spp.
(41%) and Escherichia coli 4%. Phenotypical resistance to silver nitrate was
found in Enterobacter (13%) and Klebsiella (3%) isolates. The lowest carriage
rate of sil genes was observed in blood isolates from the neonatology ward (24%),
and the highest in blood isolates from the oncology/haematology wards (66%).
Presence of sil genes was observed in international high-risk clones. Sequences
of the sil and pco clusters indicated that a single mutational event in the silS
gene could have caused the phenotypic resistance. CONCLUSION: Despite a
restricted consumption of silver-based products in Swedish health care, silver
resistance genes are widely represented in clinical isolates of Enterobacter and
Klebsiella species. To avoid further selection and spread of silver-resistant
bacteria with a high potential for healthcare-associated infections, the use of
silver-based products needs to be controlled and the silver resistance monitored.
PMID- 28506674
TI - Removal of an Infected Hip Arthroplasty Is a High-Risk Surgery: Putting Morbidity
Into Context With Other Major Nonorthopedic Operations.
AB - BACKGROUND: Two-stage revision remains the most common approach to periprosthetic
joint infection of total hip arthroplasty (THA) in the United States. The
postoperative risks associated with removal of an infected prosthesis and
placement of a spacer have not been thoroughly studied. METHODS: Patients who
underwent THA implant removal and spacer placement for infection were identified
in a large administrative database. Morbidity and mortality rates were assessed
for the 90-day postoperative period and readmission rates were assessed at 30
days postoperatively. These outcomes were then compared with those after coronary
artery bypass grafting, carotid endarterectomy, prostatectomy,
pancreatoduodenectomy (Whipple procedure), and kidney transplant. RESULTS:
Implant removal and spacer placement for THA periprosthetic joint infection (n =
10,386) had a 30-day readmission rate of 11.1% and 90-day mortality rate of 2.6%.
Major complications were seen in 15.3% patients. Postoperative morbidity was
often higher in these patients when compared with other procedures studied.
Ninety-day mortality rates were significantly higher compared with carotid
endarterectomy, prostatectomy, and kidney transplant (odds ratio [ORs] between
2.1 and 12.5; P < .0001). Readmission rates at 30 days were significantly higher
than all other groups including coronary artery bypass grafting and Whipple (ORs
between 1.4 and 8.2; P < .0001). CONCLUSION: Removal of an infected THA with
spacer placement is a high-risk surgery. This large study that includes over
10,000 patients helps quantify the risks of readmission, morbidity, and
mortality. The rates of adverse outcomes are higher than those for many
nonorthopedic operations typically considered to be major surgery.
PMID- 28506675
TI - Impact of Comorbidities on Outcome After Total Hip Arthroplasty.
AB - BACKGROUND: Patient-reported outcome scores gain increasing importance in
quantifying clinical success and procedure remuneration. Our aim was to evaluate
the impact of comorbidity on joint-specific outcome and general health in
patients undergoing elective total hip arthroplasty (THA). METHODS: Longitudinal
data on THA procedures were used to evaluate the association between comorbidity
and surgical outcome in terms of joint-specific measures and general health
(Forgotten Joint Score-12 [FJS-12], Oxford Hip Score [OHS], and Short Form-12) at
1-year follow-up. Comorbidities comprised the Charlson comorbidity index (CCI),
low back pain (LBP), pain from other joints (POJ), and body mass index. RESULTS:
We analyzed data from 251 THA patients (age: 67.7 +/- 11.8 years; 58.2% female).
Most common conditions were POJ (75.9%), LBP (55.1%), connective tissue disease
(12.1%), and diabetes (5.6%). With regard to postoperative improvement, we did
not find statistically significant differences between patients with or without
CCI comorbidities (FJS-12, +38.7 vs +43.2, P = .370; OHS, +15.6 vs +17.9, P =
.100) or POJ (FJS-12, +39.9 vs +45.1, P = .325; OHS, +17.3 vs +16.6, P = .645).
Patients with LBP showed less improvement on the FJS-12 than those without LBP
(+35.6 vs +49.1; P = .002), whereas no difference was found for the OHS (+17.9 vs
+16.5; P = .266). CONCLUSION: Patients with comorbid conditions report lower
preoperative and postoperative outcome scores compared with patients with no such
conditions; however, there was no statistically significant association of CCI
comorbidities and POJ with postoperative improvement in joint-specific outcomes.
LBP was found to have a negative impact on postoperative improvement in terms of
joint awareness.
PMID- 28506677
TI - Controller design for a class of nonlinear MIMO coupled system using multiple
models and second level adaptation.
AB - In this paper, an adaptive control method using multiple models with second level
adaptation is proposed for a class of nonlinear multi-input multi-output (MIMO)
coupled systems. Multiple estimation models are used to tune the unknown
parameters at the first level. The second level adaptation provides a single
parameter vector for the controller. A feedback linearization technique is used
to design a state feedback control. The efficacy of the designed controller is
validated by conducting real time experiment on a laboratory setup of twin rotor
MIMO system (TRMS). The TRMS setup is discussed in detail and the experiments
were performed for regulation and tracking problem for pitch and yaw control
using different reference signals. An Extended Kalman Filter (EKF) has been used
to observe the unavailable states of the TRMS.
PMID- 28506676
TI - Bile acids and gestation.
AB - There are numerous profound maternal physiological changes that occur from
conception onwards and adapt throughout gestation in order to support a healthy
pregnancy. By the time of late gestation, when circulating pregnancy hormones are
at their highest concentrations, maternal adaptations include relative
hyperlipidemia, hypercholanemia and insulin resistance. Bile acids have now been
established as key regulators of metabolism, and their role in gestational
changes in metabolism is becoming apparent. Bile acid homeostasis is tightly
regulated by the nuclear receptor FXR, which has been shown to have reduced
activity during pregnancy. This review focuses on the gestational alterations in
bile acid homeostasis that occur in normal pregnancy, which in some women can
become pathological, leading to the development of intrahepatic cholestasis of
pregnancy. As well as their important role in maternal metabolic health, we will
review bile acid metabolism in the feto-placental unit.
PMID- 28506678
TI - Adaptive super-twisting sliding mode control for a three-phase single-stage grid
connected differential boost inverter based photovoltaic system.
AB - This paper presents an adaptive super-twisting sliding mode control (STC) along
with double-loop control for voltage tracking performance of three-phase
differential boost inverter and DC-link capacitor voltage regulation in grid
connected PV system. The effectiveness of the proposed control strategies are
demonstrated under realistic scenarios such as variations in solar insolation,
load power demand, grid voltage, and transition from grid-connected to standalone
mode etc. Additional supplementary power quality control functions such as
harmonic compensation, and reactive power management are also investigated with
the proposed control strategy. The results are compared with conventional
proportional-integral controller, and PWM sliding mode controller. The system
performance is evaluated in simulation and in real-time.
PMID- 28506679
TI - Scoping Review of the Mental Health of Parents of Infants in the NICU.
AB - OBJECTIVE: To synthesize and summarize evidence regarding the mental health of
parents of infants in the NICU. DATA SOURCES: Thirteen electronic databases were
searched in October 2014 using the following terms individually and in
combination: postpartum woman, mother, NICU, preterm birth, depression, anxiety,
acute stress disorder (ASD), posttraumatic stress disorder (PTSD), and parental
stress. STUDY SELECTION: We examined the published research regarding the
experiences of parents who have infants admitted to the NICU, the mental health
problems that parents may develop, the tools that have been used to identify such
problems, and factors related to parental mental health. DATA EXTRACTION: After
the exclusion of articles according to preset criteria, we included 66 articles
in the full review. DATA SYNTHESIS: Mental health issues are common in parents of
infants in the NICU across diverse ethnocultural groups and countries. Parents
report feelings of guilt and shame, high levels of stress, mood and anxiety
symptoms, and the positive influence of specific coping strategies and social
support. The ethnocultural meanings of these experience and thus nursing
interventions may differ widely. CONCLUSION: Ongoing assessments of the mental
health of parents should be part of routine NICU care. Identification of mood and
anxiety symptoms and testing innovative interventions to address at-risk or
affected parents is imperative to ensure that there are culturally appropriate
policies and services in place to respond to the mental health needs of NICU
families.
PMID- 28506681
TI - Evaluation of carotid intima-media thickness with vascular endothelial growth
factor and malondialdehyde levels in patients with sarcoidosis.
AB - PURPOSE: To assess the impact of sarcoidosis on endothelial function by measuring
carotid intima-media thickness (CIMT) and serum levels of malondialdehyde and
vascular endothelial growth factor (VEGF). MATERIALS AND METHODS: We
prospectively analyzed 41 patients with sarcoidosis (9 men, 32 women) with a mean
age of 44.9+/-10.2 (SD) years and 34 healthy subjects (9 men, 24 women) with a
mean age of 37.26+/-8.9 (SD) years who served as a control group. Sarcoidosis
patients receiving steroids were included in Group 1 while those not under
steroid treatment were included in Group 2. CIMT measurements were performed
using B-mode ultrasound. Malondialdehyde and VEGF serum levels were obtained in
all sarcoidosis patients and control subjects. RESULTS: Both right and left CIMT
was significantly higher in Group 1 and Group 2 than in control subjects. Serum
levels of malondialdehyde and VEGF in Group 1 and Group 2 were significantly
higher than in healthy subjects. No differences in CIMT, malondialdehyde and VEGF
were found between Group 1 and Group 2. CONCLUSION: Sarcoidosis results in
increased CIMT, VEGF and malondialdehyde serum levels. However, there was no
difference in terms of CIMT, VEGF and malondialdehyde levels between sarcoidosis
patients with or without steroid treatment, suggesting that new treatment
strategies for sarcoidosis vascular involvement should consider this result.
PMID- 28506680
TI - Expanding role of percutaneous cholecystostomy and interventional radiology for
the management of acute cholecystitis: An analysis of 144 patients.
AB - PURPOSE: To investigate the rates of interval cholecystectomy and recurrent
cholecystitis after initial percutaneous cholecystostomy (PC) and identify
predictors of patient outcome after PC. MATERIALS AND METHODS: A total of 144
patients with acute cholecystitis who were treated with PC were included. There
were 96 men and 48 women, with a mean age of 71+/-13 (SD) years (range: 25-100
years). Patient characteristics, diagnostic imaging studies and results of
laboratory tests at initial presentation, clinical outcomes after the initial PC
treatment were reviewed. RESULTS: Among the 144 patients, 56 patients were
referred for acute acalculous and 88 patients for calculus cholecystitis. Five
procedure-related major complications (3.6%) were observed including bile
peritonitis (n=3), hematoma (n=1) and abscess formation (n=1). Recurrent acute
cholecystitis after initial clinical resolution and PC tube removal was observed
in 8 patients (6.0%). The rate of interval cholecystectomy was 33.6% (47/140)
with an average interval period of 100+/-482 (SD) days (range: 3-1017 days). PC
was a definitive treatment in 85 patients (60.7%) whereas 39 patients (27.9%) had
elective interval cholecystectomy without having recurrent cholecystitis. The
clinical outcomes after PC did not significantly differ between patients with
calculous cholecystitis and those with acalculous cholecystitis. Multiple prior
abdominal operations were associated with higher rates of recurrent
cholecystitis. CONCLUSION: For both acute acalculous and calculous cholecystitis,
PC is an effective and definitive treatment modality for more than two thirds of
our study patients over 3.5-year study period with low rates of recurrent disease
and interval cholecystectomy.
PMID- 28506682
TI - Colorectal cancer-inflammatory bowel disease nexus and felony of Escherichia
coli.
AB - Colorectal cancer (CRC) has a multifactorial etiology. Although the exact cause
of CRC is still elusive, recent studies have indicated microbial involvement in
its etiology. Escherichia coli has emerged as an important factor in CRC
development since the bacterium can cause changes in the gut that lead to
cancerous transformation. A number of studies indicate that chronic inflammation
induced by microorganisms, including E. coli, during inflammatory bowel disease
(IBD) predisposes an individual to CRC. The evidence that support the role of E.
coli in the etiology of CRC, through IBD, is not limited only to chronic
inflammation. The growth of E. coli as an intracellular pathogen during IBD and
CRC enable the bacteria to modulate the host cell cycle, induce DNA damage and
accumulate mutations. These are some of the contributing factors behind the
etiology of CRC. The present article considers the current status of the
involvement of E. coli, through IBD, in the etiology of CRC. We discuss how
intracellular E. coli infection can cause changes in the gut that can eventually
lead to cellular transformation. In addition, the recent management strategies
that target E. coli for prevention of CRC are also discussed.
PMID- 28506683
TI - The caspase-1 inhibitor CARD18 is specifically expressed during late
differentiation of keratinocytes and its expression is lost in lichen planus.
AB - BACKGROUND: CARD18 contains a caspase recruitment domain (CARD) via which it
binds to caspase-1 and thereby inhibits caspase-1-mediated activation of the pro
inflammatory cytokine interleukin (IL)-1beta. OBJECTIVES: To determine the
expression profile and the role of CARD18 during differentiation of keratinocytes
and to compare the expression of CARD18 in normal skin and in inflammatory skin
diseases. METHODS: Human keratinocytes were induced to differentiate in monolayer
and in 3D skin equivalent cultures. In some experiments, CARD18-specific siRNAs
were used to knock down expression of CARD18. CARD18 mRNA levels were determined
by quantitative real-time PCR, and CARD18 protein was detected by Western blot
and immunofluorescence analyses. In situ expression was analyzed in skin biopsies
obtained from healthy donors and patients with psoriasis and lichen planus.
RESULTS: CARD18 mRNA was expressed in the epidermis at more than 100-fold higher
levels than in any other human tissue. Within the epidermis, CARD18 was
specifically expressed in the granular layer. In vitro CARD18 was strongly
upregulated at both mRNA and protein levels in keratinocytes undergoing terminal
differentiation. In skin equivalent cultures the expression of CARD18 was
efficiently suppressed by siRNAs without impairing stratum corneum formation.
Epidermal expression of CARD18 was increased after ultraviolet (UV)B irradiation
of skin explants. In skin biopsies of patients with psoriasis no consistent
regulation of CARD18 expression was observed, however, in lesional epidermis of
patients with lichen planus, CARD18 expression was either greatly diminished or
entirely absent whereas in non-lesional areas expression was comparable to normal
skin. CONCLUSIONS: Our results identify CARD18 as a differentiation-associated
keratinocyte protein that is altered in abundance by UV stress. Its
downregulation in lichen planus indicates a potential role in inflammatory
reactions of the epidermis in this disease.
PMID- 28506684
TI - Study of Preanalytic and Analytic Variables for Clinical Next-Generation
Sequencing of Circulating Cell-Free Nucleic Acid.
AB - Detection of mutations in plasma circulating cell-free DNA (cfDNA) by next
generation sequencing (NGS) has opened up new possibilities for monitoring
treatment response and disease progression in patients with solid tumors.
However, implementation of cfDNA genotyping in diagnostic laboratories requires
systematic assessment of preanalytical parameters and analytical performance of
NGS platforms. We assessed the effects of peripheral blood collection tube and
plasma separation time on cfDNA yield and integrity and performance of the Ion
PGM, Proton, and MiSeq NGS platforms. cfDNA from 31 patients with diverse
advanced cancers and known tumor mutation status was deep sequenced using
targeted hotspot panels. Forty-five of 52 expected mutations and two additional
mutations (KRAS p.Q61H and EZH2 p.Y646F) were detected in plasma through a custom
bioinformatics pipeline. We observed comparable cfDNA concentration/integrity
between collection tubes within 16 hours of plasma separation and equal
analytical performance among NGS platforms, with 1% detection sensitivity for
cfDNA genotyping.
PMID- 28506685
TI - Simultaneous Genotyping of alpha-Thalassemia Deletional and Nondeletional
Mutations by Real-Time PCR-Based Multicolor Melting Curve Analysis.
AB - alpha-Thalassemia, which is caused by defective synthesis of the hemoglobin alpha
globin chains, is the most commonly inherited recessive hemoglobin abnormality.
Genetic detection of a defective alpha-globin gene is challenging because of a
variety of large deletions of the alpha-globin gene cluster and nondeletional
mutations. Separate detections of them are often required using complex and error
prone open-tube methods. We report a novel real-time PCR-based assay that can
simultaneously genotype four major deletional and three common nondeletional
mutations in two parallel reactions by using multicolor melting curve analysis.
The turnaround time of this closed-tube assay was within 3.5 hours, the limit of
detection was 5 ng of human genomic DNA per reaction, and as low as 5% mutant DNA
could be detected in the mosaic samples. The assay was evaluated using 1213
precharacterized genomic DNA samples in a double-blind manner. All seven alpha
thalassemia mutations were accurately genotyped, yielding a 99.3% concordance
with the comparison assays. The 14 discordant samples contained the HKalphaalpha
allele that was undetected by the traditional methods. Considering its rapidity,
ease of use, and accuracy, we concluded that our real-time PCR assay may be
recommended as an alternative screening and diagnostic tool for alpha
thalassemia.
PMID- 28506686
TI - Excessively delayed maternal reaction after their perception of decreased fetal
movements in stillbirths: Population-based study in Japan.
AB - BACKGROUND: Fetal movement is the most common method to evaluate fetal well
being. Furthermore, maternal perception of decreased fetal movements is
associated with perinatal demise. Previously, we showed that perception of
decreased fetal movements was the most common reason for mothers visiting the
outpatient department among those who had stillbirths in our region. Further
investigation of stillbirths with decreased fetal movements is essential to find
a possible way of preventing stillbirth. AIM: To investigate maternal reaction
time after their perceiving decreased fetal movements among stillbirths in our
region of Japan. METHODS: This is a population-based study of stillbirths in
Shiga Prefecture, Japan conducted from 2007 to 2011. We sent a questionnaire to
each obstetrician who had submitted the stillbirth certificate. We reviewed and
evaluated the questionnaires returned from the obstetricians. FINDINGS: There
were 66 cases (35%) with decreased fetal movements among 188 stillbirths in Shiga
during the study period. The number of maternal visits to outpatient department
after perception of decreased fetal movements within 24h was only seven (11%)
among 64 stillbirths diagnosed at outpatient department. CONCLUSION: We conclude
that delayed maternal visit after perceiving decreased fetal movements is
frequently observed in stillbirths. Promoting more thorough maternal education on
fetal movements, including emphasizing earlier visitation after perceiving
decreased fetal movements, may prevent stillbirths.
PMID- 28506687
TI - Human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) related
lymphomas, pathology view point.
AB - The contribution of Epstein Barr virus (EBV) and Kaposi sarcoma herpes virus
(KSHV) to the development of specific types of malignant lymphomas occurring in
the human immunodeficiency virus (HIV) setting has been extensively studied since
the beginning of the HIV epidemic 35 years ago. The introduction of highly active
antiretroviral therapies (HAART) in 1996 has changed dramatically the incidence
of HIV-related malignancies. Nevertheless, malignant lymphomas continue to be the
major group of malignances observed in HIV infected individuals, and the most
common cause of cancer related-deaths. Common features of the predominant B-cell
lymphomas in the HIV+ setting are the frequent plasmacytoid morphology of the
neoplastic cells, advanced stage, aggressive disease and frequent extranodal
involvement. In this article, we review the evolving concepts and definitions of
the various EBV-associated lymphomas in HIV+ patients, including diffuse large B
cell lymphoma, Burkitt lymphoma, classical Hodgkin lymphoma, plasmablastic
lymphoma and primary effusion lymphoma. The current knowledge regarding the
pathogenesis of these malignancies, the interplay between HIV and EBV co
infection in the development of certain HIV related lymphomas, and the emerging
paradigm that suggests that HIV may play a direct role in lymphomagenesis are
explored as well.
PMID- 28506688
TI - Human immunodeficiency virus and fungal infections.
AB - The discovery of HIV was largely due to the presence of Pneumocystis pneumonia
(PCP) in young patients that did not have the usual known causes of immune
deficiencies in the early 1980s. Currently, treatment with highly active anti
retroviral therapy (HAART) and the use of prophylaxis for PCP have lowered the
frequency of fungal infections; however, these infections continue to cause
morbidity and mortality in those patients that fall out or are not in care. The
frequency of specific fungal diseases in HIV patients will depend on the
prevalence of fungi in the particular geographic location. Nowadays, superficial
and invasive Candida infections, PCP, and cryptococci are the most frequent
fungal infections seen in HIV positive patients worldwide. The role of pathology
in diagnosing fungal infections is crucial because a lesion may be biopsied
without obtaining mycology cultures, certain organisms may take several weeks to
grow, or the sample sent to the mycology laboratory may not have the organism.
Following we will describe fungal infections that are particularly frequent in
HIV infected patients and their key pathological features.
PMID- 28506690
TI - Romidepsin induces caspase-dependent cell death in human neuroblastoma cells.
AB - Neuroblastoma is the most common extracranial pediatric solid tumor, arising from
the embryonic sympathoadrenal lineage of the neural crest, and is responsible for
15% of childhood cancer deaths. Although survival rates are good for some
patients, those children diagnosed with high-risk neuroblastoma have survival
rates as low as 35%. Thus, neuroblastoma remains a significant clinical challenge
and the development of novel therapeutic strategies is essential. Given that
there is widespread epigenetic dysregulation in neuroblastoma, epigenetic
pharmacotherapy holds promise as a therapeutic approach. In recent years, histone
deacetylase (HDAC) inhibitors, which cause selective activation of gene
expression, have been shown to be potent chemotherapeutics for the treatment of a
wide range of cancers. Here we examined the ability of the FDA-approved drug
Romidepsin, a selective HDAC1/2 inhibitor, to act as a cytotoxic agent in
neuroblastoma cells. Treatment with Romidepsin at concentrations in the low
nanomolar range induced neuroblastoma cell death through caspase-dependent
apoptosis. Romidepsin significantly increased histone acetylation, and
significantly enhanced the cytotoxic effects of the cytotoxic agent 6
hydroxydopamine, which has been shown to induce cell death in neuroblastoma cells
through increasing reactive oxygen species. Romidepsin was also more potent in
MYCN-amplified neuroblastoma cells, which is an important prognostic marker of
poor survival. This study has thus demonstrated that the FDA-approved
chemotherapeutic drug Romidepsin has a potent caspase-dependent cytotoxic effect
on neuroblastoma cells, whose effects enhance cell death induced by other
cytotoxins, and suggests that Romidepsin may be a promising chemotherapeutic
candidate for the treatment of neuroblastoma.
PMID- 28506689
TI - Genetic Factors Interact With Tobacco Smoke to Modify Risk for Inflammatory Bowel
Disease in Humans and Mice.
AB - BACKGROUND & AIMS: The role of tobacco smoke in the etiology of inflammatory
bowel disease (IBD) is unclear. We investigated interactions between genes and
smoking (gene-smoking interactions) that affect risk for Crohn's disease (CD) and
ulcerative colitis (UC) in a case-only study of patients and in mouse models of
IBD. METHODS: We used 55 Immunochip-wide datasets that included 19,735 IBD cases
(10,856 CD cases and 8879 UC cases) of known smoking status. We performed 3 meta
analyses each for CD, UC, and IBD (CD and UC combined), comparing data for never
vs ever smokers, never vs current smokers, and never vs former smokers. We
studied the effects of exposure to cigarette smoke in Il10-/- and Nod2-/- mice,
as well as in Balb/c mice without disruption of these genes (wild-type mice).
Mice were exposed to the smoke of 5 cigarettes per day, 5 days a week, for 8
weeks, in a ventilated smoking chamber, or ambient air (controls). Intestines
were collected and analyzed histologically and by reverse transcription
polymerase chain reaction. RESULTS: We identified 64 single nucleotide
polymorphisms (SNPs) for which the association between the SNP and IBD were
modified by smoking behavior (meta-analysis Wald test P < 5.0 * 10-5;
heterogeneity Cochrane Q test P > .05). Twenty of these variants were located
within the HLA region at 6p21. Analysis of classical HLA alleles (imputed from
SNP genotypes) revealed an interaction with smoking. We replicated the
interaction of a variant in NOD2 with current smoking in relation to the risk for
CD (frameshift variant fs1007insC; rs5743293). We identified 2 variants in the
same genomic region (rs2270368 and rs17221417) that interact with smoking in
relation to CD risk. Approximately 45% of the SNPs that interact with smoking
were in close vicinity (<=1 Mb) to SNPs previously associated with IBD; many were
located near or within genes that regulate mucosal barrier function and immune
tolerance. Smoking modified the disease risk of some variants in opposite
directions for CD vs UC. Exposure of Interleukin 10 (il10)-deficient mice to
cigarette smoke accelerated development of colitis and increased expression of
interferon gamma in the small intestine compared to wild-type mice exposed to
smoke. NOD2-deficient mice exposed to cigarette smoke developed ileitis,
characterized by increased expression of interferon gamma, compared to wild-type
mice exposed to smoke. CONCLUSIONS: In an analysis of 55 Immunochip-wide
datasets, we identified 64 SNPs whose association with risk for IBD is modified
by tobacco smoking. Gene-smoking interactions were confirmed in mice with
disruption of Il10 and Nod2-variants of these genes have been associated with
risk for IBD. Our findings from mice and humans revealed that the effects of
smoking on risk for IBD depend on genetic variants.
PMID- 28506692
TI - Sex differences in microglial appetites during development: Inferences and
implications.
PMID- 28506691
TI - Urinary lysophopholipids are increased in diabetic patients with nephropathy.
AB - Diabetic nephropathy (DN) is a major cause of chronic kidney disease that
frequently leads to end stage renal failure. Lysophosphatidic acid (LPA) and
lysophosphatidylcholine (LPC) are lysophospholipid mediators shown to accumulate
in kidney and to promote renal inflammation and tubulo-interstitial fibrosis in
diabetic rodent models. Here we assessed whether LPA and LPC were associated to
the development of nephropathy in diabetic human patients. Several molecular
species of LPA and LPC were quantified by LC/MS-MS in urine and plasma from type
2 diabetic patients with (cases; n=41) or without (controls, n=41) nephropathy
symptoms (micro/macro-albuminuria and eGFR<60ml/min/1.73m2). Cases and controls
were matched for sex, age and diabetes duration. Six species were detected in
urine for both LPA and LPC, LPA16:0, LPA20:4, LPC16:0, LPC18:0, LPC18:1, and
LPC18:2 that were significantly more concentrated in cases than in controls.
Total LPC and LPA (sum of detected species) were significantly and exclusively
associated with albuminuria (P<0.0001 and P=0.0009 respectively) and were
significantly higher in the 3rd when compared to the 1st albuminuria tertile in
cases. Plasma lysophospholipids showed a different species profile urine and
their concentrations were not different between cases and controls. In
conclusion, urine concentration of lysophospholipids increases in diabetic
patients with DN as the likely result of their co-excretion with albumin combined
with possible local production by kidney. Because LPA and LPC are known to
promote renal inflammation and tubulo-interstitial fibrosis, their increased
production in DN could participate to the development of kidney damage associated
with diabetes.
PMID- 28506693
TI - Survival prediction of non-small cell lung cancer patients using radiomics
analyses of cone-beam CT images.
AB - BACKGROUND AND PURPOSE: In this study we investigated the interchangeability of
planning CT and cone-beam CT (CBCT) extracted radiomic features. Furthermore, a
previously described CT based prognostic radiomic signature for non-small cell
lung cancer (NSCLC) patients using CBCT based features was validated. MATERIAL
AND METHODS: One training dataset of 132 and two validation datasets of 62 and
94stage I-IV NSCLC patients were included. Interchangeability was assessed by
performing a linear regression on CT and CBCT extracted features. A two-step
correction was applied prior to model validation of a previously published
radiomic signature. Results 13.3% (149 out of 1119) of the radiomic features,
including all features of the previously published radiomic signature, showed an
R2 above 0.85 between intermodal imaging techniques. For the radiomic signature,
Kaplan-Meier curves were significantly different between groups with high and low
prognostic value for both modalities. Harrell's concordance index was 0.69 for CT
and 0.66 for CBCT models for dataset 1. Conclusions The results show that a
subset of radiomic features extracted from CT and CBCT images are interchangeable
using simple linear regression. Moreover, a previously developed radiomics
signature has prognostic value for overall survival in three CBCT cohorts,
showing the potential of CBCT radiomics to be used as prognostic imaging
biomarker.
PMID- 28506694
TI - Optogenetics gets to the heart: A guiding light beyond defibrillation.
AB - Optogenetics provides a tool for controlling the electrical activity of excitable
cells by means of the interaction of light with light-gated ion channels. Despite
the fact that optogenetics has been intensively utilized in the neurosciences, it
has been more rarely employed as an instrument for studying cardiac
pathophysiology. However, the advantages of optical approaches to perturb cardiac
electrical activity are numerous, especially when the spatio-temporal qualities
of light are utterly exploited. Here, we review the main breakthroughs employing
optogenetics to perturb cardiac pathophysiology and attempt a comparison of
methods and procedures that have employed optogenetics in the heart. We
particularly focus on light-based defibrillation strategies that represent one of
the latest achievements in this field. We highlight the important role of
advanced optical methods for detecting and stimulating electrical activity for
optimizing defibrillation strategies and, more generally, for dissecting novel
insights in cardiac physiology. Finally, we discuss the main future perspectives
that we envision for optogenetics in the heart, both in terms of translational
applications and for addressing fundamental questions of cardiac function.
PMID- 28506695
TI - D816V mutation in the KIT gene activation loop has greater cell-proliferative and
anti-apoptotic ability than N822K mutation in core-binding factor acute myeloid
leukemia.
AB - In core-binding factor acute myeloid leukemia (CBF-AML), there have been
conflicting reports regarding the status as an unfavorable prognostic factor of
mutation in the KIT gene, the significance of which remains unclear. We
previously reported that prognoses differ between the KIT D816V and N822K
mutations. In the present study, we compared in vitro the cell-proliferative and
anti-apoptotic ability of D816V and N822K. We transduced these KIT mutations into
the interleukin-3-dependent cell line TF-1 (TF-1 KITD816V, TF-1 KITN822K). When
these KIT mutations were transduced into TF-1 cells, the cells acquired a
proliferative ability independent of growth factor, which was significantly
higher in TF-1 KITD816V than in TF-1 KITN822K (p = 0.022). When Ara-C was added
in the absence of growth factor, Annexin V assay revealed that TF-1 KITD816V was
associated with a significantly lower proportion of apoptotic cells than TF-1
KITN822K (p < 0.001). Regarding signal transduction pathways, both KIT D816V and
KIT N822K underwent autophosphorylation in the absence of growth factor. This was
followed in KIT D816V by downstream activation of the SRC family kinase pathway
in addition to the Janus kinase/signal transducers and activators of
transcription (JAK/STAT) pathway, and in KIT N822K by downstream activation of
the mitogen-activated protein kinase (MAPK) pathway in addition to the JAK/STAT
pathway. These findings establish that D816V and N822K mutations are situated
closely on the KIT receptor activation loop, but D816V has greater cell
proliferative and anti-apoptotic ability than N822K.
PMID- 28506696
TI - Current approaches for avoiding the limitations of circulating tumor cells
detection methods-implications for diagnosis and treatment of patients with solid
tumors.
AB - Eight million people die of cancer each year and 90% of deaths are caused by
systemic disease. Circulating tumor cells (CTCs) contribute to the formation of
metastases and thus are the subject of extensive research and an abiding interest
to biotechnology and pharmaceutical companies. Recent technological advances have
resulted in greatly improved CTC detection, enumeration, expansion, and culture
methods. However, despite the fact that nearly 150 years have passed since the
first detection and description of CTCs in human blood and enormous technological
progress that has taken place in this field, especially within the last decade,
few CTC detection methods have been approved for routine clinical use. This
reflects the substantial methodological problems related to the nature of these
cells, their heterogeneity, and diverse metastatic potential. Here, we provide an
overview of CTC phenotypes, including the plasticity of CTCs and the relevance of
inflammation and cell fusion phenomena for CTC biology. We also review the
literature on CTC detection methodology-its recent improvements, clinical
significance, and efforts of its clinical application in cancer patients
management. At present, CTC detection remains a challenging diagnostic approach
as a result of numerous current methodological limitations. This is especially
problematic during the early stages of the disease due to the small numbers of
CTCs released into the blood of cancer patients. Nonetheless, the rapid
development of novel techniques of CTC detection and enumeration in peripheral
blood is expected to expedite their implementation in the clinical setting. It is
of utmost importance to understand the biology of CTCs and their distinct
populations as a prerequisite for achieving this ultimate goal.
PMID- 28506697
TI - Inflammation and hemostasis in older octogenarians: implication in 5-year
survival.
AB - Social changes and medical advances have increased longevity, but the conditions
governing healthy vs unhealthy cardiovascular (CV) aging are not fully known.
Factors beyond classical CV risk factors may have an important unrecognized
value. We sought to identify proteins differentially expressed in healthy
octogenarians (HOs) without a history of cardiovascular disease (CVD) and
preserved functional and cognitive state compared with octogenarians with a
history of CVD and cognitive decline (UHOs) using a systems biology approach, and
investigated how these proteins relate to CV mortality at 5-year follow-up.
Plasmas obtained from older octogenarians (87 +/- 0 years) were analyzed by 2-DE
+ MS and bioinformatic pathway analysis in HOs (N = 38) and UHOs with cognitive
(MEC<25) and functional (Barthel<90) decline and a previous ischemic event (acute
myocardial infarction and/or stroke; N = 27). Results were validated by ELISA in
HOs and UHOs and in an additional group of older octogenarians without cognitive
impairment but with a previous CVD manifestation (HO-CVD; N = 35). UHOs showed a
coordinated change in several inflammation-related proteins (AMBP, RBP4, and
ITIH4; P < 0.05), together with a significant increase in the major inducer of
the acute-phase reaction, interleukin-6 (P = 0.03). UHOs also showed a
coordinated increase in hemostatic proteins that was associated with an
impairment of fibrinolysis and an increased 5-year CV mortality (P = 0.003). The
combination of inflammation (ITIH4 and interleukin-6) and hemostatic markers (D
dimer, A2AP, and coagulation factor XIII) was able to discriminate the presence
of an unhealthy phenotype in the elderly (AUC = 0.750; P = 0.001). Unhealthy
older octogenarians show increased levels of several plasma proteins of
inflammation and coagulation. In older octogenarians, the increase in hemostatic
markers indicated an increase in 5-year CV mortality at follow-up.
PMID- 28506698
TI - Antiproliferative and cytotoxic effects of green coffee and yerba mate extracts,
their main hydroxycinnamic acids, methylxanthine and metabolites in different
human cell lines.
AB - : This work aimed at studying the effects of green coffee bean (GCBE) and yerba
mate (YME) extracts, their main phenolic components (5-caffeoylquinic acid, 5
CQA; 3,5-dicaffeoylquinic acid, 3,5-DCQA) and metabolites (ferulic acid, FA;
caffeic acid, CA; dihydrocaffeic acid, DHCA; and dihydroferulic acid, DHFA) along
with caffeine (CAF) on the viability and proliferation of different human cell
lines. Extracts (10-1000 MUg/mL) and standards (10-1000 MUM) were assayed in
colon (Caco-2), lung (A549), oesophageal (OE-33), urinary bladder (T24) human
carcinoma cells, and a non-cancer cell line (CCD-18Co). YME significantly reduced
viability of cancer cells at all assayed concentrations, the higher doses also
reducing cell proliferation. GCBE effects on cell viability were more effective
at 100 and 1000 MUg/mL, showing modest effects on cell proliferation. The highest
doses of 5-CQA and 3,5-DCQA reduced cell viability and proliferation in all cell
lines, whereas FA, DHCA and DHFA had lower and variable effects. Caffeine had no
effect. Dietary-attainable concentrations (0.1, 1 and 10 MUg/mL) of YME were
tested for cytotoxicity and reactive oxygen species generation, showing no
cytotoxic effect. Low concentrations of all tested compounds were non-cytotoxic
to CCD-18Co cells. CONCLUSION: YME and to a lower degree GCBE, their phenolic
components and metabolites may decrease cancer cell viability and proliferation.
PMID- 28506700
TI - Synergistic antimutagenic effect of isothiocyanates against varied mutagens.
AB - Although plant foods provide an array of nutrients in the human diet, our
knowledge of how these nutrients are interacting among each other at molecular
level is limited. Among these, glucosinolates are the most important secondary
metabolites, which are readily hydrolyzed to a variety of products including
isothiocyanates. The current study emphasizes on the antimutagenic potential of
three isothiocyanates (ITCs) viz. allyl, benzyl and 3-butenyl ITCs (individually
and in binary combinations) in Ames Salmonella histidine reversion assay using
Salmonella typhimurium TA98 and TA100 tester strains. Three different mutagens
were used in the study including two direct acting mutagens [4-nitro-o
phenylenediamine (frame shift mutagen) and sodium azide (base substitution
mutagen)] and one indirect acting mutagen [2-aminofluorene]. Furthermore, S9
fraction from rat liver microsomes was used to mimic the mammalian system. The
study points towards the ability of ITCs to act as potent inhibitors of
mutagenicity induced by different mutagens. Benzyl ITC was found to be the most
effective among the three. Computation of combination effects was done on the
basis of combination index values. It was observed that ITCs in combination
induced a stronger antimutagenic response and that too at relatively low
concentrations, without any signs of toxicity.
PMID- 28506699
TI - CRA(Crosolic Acid) isolated from Actinidia valvata Dunn.Radix induces apoptosis
of human gastric cancer cell line BGC823 in vitro via down-regulation of the NF
kappaB pathway.
AB - A natural ursolic compound, 2alpha,3beta-dihydroxy-urs-12-en-28-oic acid
(corosolic acid, CRA) was isolated from the root of Actinidia valvata Dunn. (A.
valvata Radix). Since a large number of triterpenoid compound has marked
anticancer effects toward various types of cancer cell lines in vitro, this study
was carried out to investigate the anticancer effect of CRA in human gastric
cancer cell line BGC823 cells and the underlying apoptotic mechanism of CRA was
examined in BGC823 cell lines. The results showed that CRA significantly
suppressed the viability of BGC823 cells in a concentration- and time-dependent
manner. CRA also significantly increased the sub G1 population by cell cycle
analysis in a concentration dependent manner. Exposure to CRA decreased p65, bcl
2, Fas, smac mRNA and protein expression, and increased IkappaBalpha, bax,
survivin mRNA and protein expression. Results of immunofluorescence staining and
EMSA further indicated CRA induced apoptosis by inhibiting nuclear translocation
of nuclear factor NF-kappaB subunit p65. Consistently overall, our findings
suggest that CRA induces apoptosis via inhibition of NF-kappaB (p65) expression
level and activation of IkappaBalpha in BGC cells as a potent anticancer
candidate for gastric cancer treatment.
PMID- 28506701
TI - Case-Control Study of Intra-arterial Verapamil for Intraprostatic Anastomoses to
Extraprostatic Arteries in Prostatic Artery Embolization for Benign Prostatic
Hypertrophy.
AB - PURPOSE: It is hypothesized that intra-arterial administration of verapamil is a
safe and effective way to reverse the flow in intraprostatic anastomoses to
extraprostatic arteries without compromising treatment outcomes in prostatic
artery embolization (PAE) for benign prostatic hypertrophy (BPH). MATERIALS AND
METHODS: A prospective study of 62 prostate sides in 31 consecutive patients
(median age, 66 y; range, 60-71 y) with symptomatic BPH was undertaken. Median
prostate volume was 72.4 mL (range, 48.8-85.8 mL), median International Prostate
Symptom Score was 21 (range, 15-23), and median urine peak flow rate was 4 mL/s
(range, 2-6 mL/s). The arterial anastomoses were classified as types I-III
according to vascular morphology. Treatment safety was assessed in terms of
adverse events and complications, and treatment effectiveness was assessed in
terms of success rate of angiographic flow reversal. RESULTS: The PAE procedure
was successfully completed in all 31 patients (100%). Adverse events in both
groups were transient and mild and did not necessitate prolonged hospitalization.
There was no clinical evidence of any significant nontarget ischemic complication
in either group. Intraprostatic anastomosis was diagnosed in 19 of 31 patients
(61.3%) and 22 of 62 prostate sides (35.5%). Success rates of verapamil treatment
were 88.9% overall (20 of 22) and 100% (19 of 19) in type II and III anastomoses.
There was no difference between the treatment group and the control group in
clinical, urologic, and imaging outcomes of PAE. CONCLUSIONS: Intra-arterial
verapamil treatment was probably safe and effective in causing flow reversal in
type II and III intraprostatic anastomoses and in preventing ischemic
complications in PAE for BPH without compromising PAE outcomes.
PMID- 28506702
TI - Cognitive and adaptive measurement endpoints for clinical trials in
mucopolysaccharidoses types I, II, and III: A review of the literature.
AB - Sensitive, reliable measurement instruments are critical for the evaluation of
disease progression and new treatments that affect the brain in the
mucopolysaccharidoses (MPS). MPS I, II, and III have early onset clinical
phenotypes that affect the brain during development and result in devastating
cognitive decline and ultimately death without treatment. Comparisons of outcomes
are hindered by diverse protocols and approaches to assessment including
applicability to international trials necessary in rare diseases. We review both
cognitive and adaptive measures with the goal of providing evidence to a Delphi
panel to come to a consensus about recommendations for clinical trials for
various age groups. The results of the consensus panel are reported in an
accompanying article. The following data were gathered (from internet resources
and from test manuals) for each measure and summarized in the discussion:
reliability, validity, date and adequacy of normative data, applicability of the
measure's metrics, cross cultural validity including translations and
adaptations, feasibility in the MPS population, familiarity to sites, sensitivity
to change, and interpretability. If, resulting from this consensus, standard
protocols are used for both natural history and treatment studies, patients,
their families, and health care providers will benefit from the ability to
compare study outcomes.
PMID- 28506703
TI - Abnormal asymmetry of white matter tracts between ventral posterior cingulate
cortex and middle temporal gyrus in recent-onset schizophrenia.
AB - INTRODUCTION: Previous studies have reported abnormalities in the ventral
posterior cingulate cortex (vPCC) and middle temporal gyrus (MTG) in
schizophrenia patients. However, it remains unclear whether the white matter
tracts connecting these structures are impaired in schizophrenia. Our study
investigated the integrity of these white matter tracts (vPCC-MTG tract) and
their asymmetry (left versus right side) in patients with recent onset
schizophrenia. METHOD: Forty-seven patients and 24 age-and sex-matched healthy
controls were enrolled in this study. We extracted left and right vPCC-MTG tract
on each side from T1W and diffusion MRI (dMRI) at 3T. We then calculated the
asymmetry index of diffusion measures of vPCC-MTG tracts as well as volume and
thickness of vPCC and MTG using the formula: 2*(right-left)/(right+left). We
compared asymmetry indices between patients and controls and evaluated their
correlations with the severity of psychiatric symptoms and cognition in patients
using the Positive and Negative Syndrome Scale (PANSS), video-based social
cognition scale (VISC) and the Wechsler Adult Intelligence Scale (WAIS-III).
RESULTS: Asymmetry of fractional anisotropy (FA) and radial diffusivity (RD) in
the vPCC-MTG tract, while present in healthy controls, was not evident in
schizophrenia patients. Also, we observed that patients, not healthy controls,
had a significant FA decrease and RD increase in the left vPCC-MTG tract. There
was no significant association between the asymmetry indices of dMRI measures and
IQ, VISC, or PANSS scores in schizophrenia. CONCLUSION: Disruption of asymmetry
of the vPCC-MTG tract in schizophrenia may contribute to the pathophysiology of
schizophrenia.
PMID- 28506704
TI - A method to achieve extended cannabis abstinence in cannabis dependent patients
with schizophrenia and non-psychiatric controls.
AB - BACKGROUND: Cannabis use disorders (CUD) are common in schizophrenia (~25%)
compared to the general population (~3%). Tetrahydrocannabinol (THC), the
principal psychoactive component in cannabis is fat-soluble, resulting in an
extended period for cannabinoid elimination. While detection of cannabinoids in
urine is indicative of prior cannabis exposure, time of last use is difficult to
verify sustained abstinence for extended periods (e.g., 28-days) in chronic
cannabis users. Therefore, we evaluated the utility of a sustained cannabis
abstinence paradigm in patients with schizophrenia and non-psychiatric controls.
METHODS: Cannabis dependent patients (n=19) and controls (n=20) underwent 28-days
of monitored cannabis abstinence facilitated with contingency management. Urine
samples were taken twice weekly. Abstinence was evaluated using 1) Self-report;
2) Qualitative biochemical confirmation using MEDTOX; and 3) in a subset of
participants (schizophrenia, n=13; controls, n=13) gas chromatography-mass
spectrometry (GC-MS) was performed to obtain quantitative creatinine-normalized
carboxy-THC (THC-COOH) metabolite levels <20ng/mL). Subjective assessments were
used to assess behavioral correlates of cannabis abstinence and further supported
time-dependent abstinence trajectories. RESULTS: Abstinence rates of 42.1% (8/19)
in patients and 55% (11/19) in controls (p=0.53) were observed. Increased
cannabis withdrawal symptoms in both patients and controls supported abstinence.
DISCUSSION: Our results suggest a feasible method for identification of short
term cannabis abstinence in individuals with schizophrenia at rates comparable to
controls. Monitoring sustained abstinence may have implications for potential
interventions for CUDs in schizophrenia.
PMID- 28506705
TI - The interaction of gender and cannabis in early phase psychosis.
AB - Cannabis is the third most common recreational drug used world-wide after tobacco
and alcohol. Globally, cannabis legalization is becoming more common. In light of
its known link to psychosis development, it is imperative that we are well
informed regarding the impact of cannabis on the course of psychosis, in both
males and females. However, the majority of the work to date on the role of
cannabis in psychosis outcomes has not had a gender focus, important when
considering patient specific treatments. This review examines what is currently
known, from gender focused studies, about the interaction of gender, cannabis use
and psychotic disorders.
PMID- 28506706
TI - Cognitive and functional deficits in people with schizophrenia: Evidence for
accelerated or exaggerated aging?
AB - Cognitive and functional deficits are commonly seen in people with schizophrenia.
The profile of these impairments has a resemblance to the cognitive changes seen
in healthy aging. In specific, many of the cognitive ability domains that change
the most with aging in healthy people are the most salient of these deficits seen
in people with schizophrenia, including prominent deficits in processing speed,
working memory, and episodic memory. Functional deficits seen in schizophrenia
are also similar to those seen in healthy aging. There is a relationship between
multiple psychotic relapses and treatment resistance and longitudinal cognitive
and functional changes in schizophrenia, with this relationship starting early in
the course of illness. Cognitive performance in people with schizophrenia may be
consistent with accelerated or premature aging. People with schizophrenia perform
similarly to healthy people who are 3 or more decades older on indices of both
cognition and their everyday functional skills. Some people with schizophrenia
show exaggerated cognitive changes as well. Cognitive and functional performance
worsens at the outset of the illness in schizophrenia compared to premorbid
functioning, meaning that these deficits are not due to development disabilities.
There are multiple medical and substance abuse comorbidities in schizophrenia and
although these comorbidities affect cognitive functioning, they are not
completely responsible for age-related changes.
PMID- 28506707
TI - Complex mismatch negativity to tone pair deviants in long-term schizophrenia and
in the first-episode schizophrenia spectrum.
AB - Mismatch negativity (MMN) is an event-related potential to stimulus change. MMN
to infrequent deviant tones that differs in a simple physical parameter from
repetitive standard tones is reduced in patients with long-term schizophrenia
(Sz; d=~1). However, this simple MMN is not uniformly reduced at the first
episode of schizophrenia-spectrum psychosis (FESz; d<0.1 for pitch; <0.4 for
duration). Deviant stimuli that violate pattern rules also evoke MMN. This
complex MMN is evoked by deviations in the relation of sounds to each other. The
simplest pattern involves tone pairs. Although the pitch of first tone in the
pair varies, the second tone's pitch always follows a rule (e.g., always 3
semitones higher). We measured complex MMN to deviant tone pairs that descended
in pitch among standard tone pairs that ascended in pitch, never before examined
in Sz or in FESz. Experiment 1 showed significant reductions in complex MMN in 20
Sz compared to 22 matched controls. Experiment 2 replicated smaller complex MMN
in a shorter protocol in 24 Sz compared to 21 matched controls, but showed no
significant complex MMN reduction in 21 FESz compared to 21 matched controls.
Although reduced in Sz, indicating deficits in generation of a simple acoustic
pattern rule, the tone pair complex MMN was within normal limits in FESz. This
suggests that more complex perceptual pattern analysis processes are, at least
partially, still intact at the first break. Future work will determine at what
point of pattern complexity subtle auditory perception pathophysiology will be
revealed in FESz.
PMID- 28506708
TI - Electron microscopy approach for the visualization of the epithelial and
endothelial glycocalyx.
AB - This study presents a methodological approach for the visualization of the
glycocalyx by electron microscopy. The glycocalyx is a three dimensional network
mainly composed of glycolipids, glycoproteins and proteoglycans associated with
the plasma membrane. Since less than a decade, the epithelial and endothelial
glycocalyx proved to play an important role in physiology and pathology,
increasing its research interest especially in vascular functions. Therefore,
visualization of the glycocalyx requires reliable techniques and its preservation
remains challenging due to its fragile and dynamic organization, which is highly
sensitive to the different process steps for electron microscopy sampling. In
this study, chemical fixation was performed by perfusion as a good alternative to
conventional fixation. Additional lanthanum nitrate in the fixative enhances
staining of the glycocalyx in transmission electron microscopy bright field and
improves its visualization by detecting the elastic scattered electrons, thus
providing a chemical contrast.
PMID- 28506709
TI - Behavior of macrophage and osteoblast cell lines in contact with the beta-TCP
biomaterial (beta-tricalcium phosphate).
AB - Beta-tricalcium phosphate (beta-TCP) is a synthetic ceramic used for filling bone
defects. It is a good alternative to autologous grafts since it is biocompatible,
resorbable and osteoconductive. Previous in vivo studies have shown that
macrophages are one of the first cells coming in contact with the biomaterial
followed by osteoclasts and osteoblasts that will elaborate new bone packets.
Studies have focused on osteoclast morphology and very few of them have
investigated the role of macrophages. The aims of this study were to characterize
(i) the biomaterial surface; (ii) the in vitro behavior of macrophages (J774.2
and Raw264.7 cells) using the description of cell morphology by scanning electron
microscopy (SEM) at 7 and 14 days; (iii) the behavior of osteoblasts (SaOs-2 and
MC3T3-E1 cells) seeded at the surface of the biomaterial 24, 48 and 72hours by
SEM and confocal microscopy. Cell proliferation was analyzed by MTT assays.
Viability and affinity of the macrophages for beta-TCP were found significantly
increased after 7 and 14d. MC3T3-E1 cells were anchored and stretched onto the
beta-TCP surface as early as 24h with a high proliferation rate (+190%) when
compared to the surface of a well plate. SaOs-2 exhibited the same morphological
profile at 72h. Proliferation became significantly higher compared to the plastic
surface at only 72h (+129%). This study emphasises the importance of choice of
the cell line used in exploring the osteoconductive and osteoinductive properties
of a biomaterial. Additional studies are needed to analyze differentiation of
macrophages into giant multinucleated cells and how the biomaterial surface
influences osteoblast differentiation.
PMID- 28506710
TI - Outcomes after repeat ablation of ventricular tachycardia in structural heart
disease: An analysis from the International VT Ablation Center Collaborative
Group.
AB - BACKGROUND: Data evaluating repeat radiofrequency ablation (>1RFA) of ventricular
tachycardia (VT) are limited. OBJECTIVE: The purpose of this study was to
determine the safety and outcomes of VT >1RFA in patients with structural heart
disease. METHODS: Patients with structural heart disease undergoing VT RFA at 12
centers with data on prior RFA history were included. Characteristics and
outcomes were compared between first-time (1RFA) and >1RFA patients. RESULTS: Of
1990 patients, 740 had >1RFA (mean 1.4 +/- 0.9, range 1-10). >1RFA vs 1RFA
patients did not differ with regard to age (62 +/- 13 years vs 62 +/- 13 years),
left ventricular ejection fraction (33% +/- 13% vs 34% +/- 13%), or sex (88% vs
87% men), but they more often were nonischemic (53% vs 41%), had implantable
cardioverter-defibrillator shocks (70% vs 63%) or VT storm (38% vs 33%), and had
been treated with amiodarone (55% vs 48%) or >=2 antiarrhythmic drugs (22% vs
14%). >1RFA procedures were longer (300 +/- 122 minutes vs 266 +/- 110 minutes),
involved more epicardial access (41% vs 21%), induced VTs (2.4 +/- 2.2 vs 1.9 +/-
1.6) and only unmappable VTs (15% vs 9%), and VT was more often inducible after
RFA (42% vs 33%, all P <.03). Total complications were higher for >1RFA vs 1RFA
(8% vs 5%, P <.01), mostly related to pericardial effusion (2.4% vs 1.3%, P =
.07) and venous thrombosis (0.8% vs 0.2%, P = .06). VT recurrence was higher for
>1RFA vs 1RFA (29% vs 24%, P <.001). Survival was worse for >1RFA vs 1RFA if VT
recurred (67% vs 78%, P = .003) but was equivalent if successful (93% vs 92%, P =
.96). CONCLUSION: Patients requiring repeat VT ablation differ significantly from
those undergoing first-time ablation. Despite more challenging ablation
characteristics, VT-free survival after repeat ablations is encouraging.
Mortality is comparable if VT does not recur after RFA at specialized centers.
PMID- 28506711
TI - Screening for sepsis in general hospitalized patients: a systematic review.
AB - BACKGROUND: Sepsis is a condition widely observed outside critical care areas.
AIM: To examine the application of sepsis screening tools for early recognition
of sepsis in general hospitalized patients to: (i) identify the accuracy of these
tools; (ii) determine the outcomes associated with their implementation; and
(iii) describe the implementation process. METHODS: A systematic review method
was used. PubMed, CINAHL, Cochrane, Scopus, Web of Science, and Embase databases
were systematically searched for primary articles, published from January 1990 to
June 2016, that investigated screening tools or alert mechanisms for early
identification of sepsis in adult general hospitalized patients. The review
protocol was registered with PROSPERO (CRD42016042261). FINDINGS: More than 8000
citations were screened for eligibility after duplicates had been removed. Six
articles met the inclusion criteria testing two types of sepsis screening tools.
Electronic tools can capture, recognize abnormal variables, and activate an alert
in real time. However, accuracy of these tools was inconsistent across studies
with only one demonstrating high specificity and sensitivity. Paper-based, nurse
led screening tools appear to be more sensitive in the identification of septic
patients but were only studied in small samples and particular populations. The
process of care measures appears to be enhanced; however, demonstrating improved
outcomes is more challenging. Implementation details are rarely reported.
Heterogeneity of studies prevented meta-analysis. CONCLUSION: Clinicians,
researchers and health decision-makers should consider these findings and
limitations when implementing screening tools, research or policy on sepsis
recognition in general hospitalized patients.
PMID- 28506712
TI - Lung Metastases from Esophageal Granular Cell Tumor: An Undoubted Criterion for
Malignancy.
PMID- 28506713
TI - The Emperor's new topology: Comment on "Topodynamics of metastable brains" by
Arturo Tozzi et al.
PMID- 28506714
TI - The Physics Inside our Brain: Comment on "Topodynamics of Metastable Brains" by
Arturo Tozzi et al.
PMID- 28506716
TI - MEK Retinopathy. Clinical case reports.
AB - CASE REPORTS: Three clinical cases are presented of MEK retinopathy associated
with the combination of cobimetinib and vemurafenib characterised by alteration
of the retinal pigment epithelium and neurosensory detachment. Two of the cases
conserved the vision of the unit, and the third developed a large bilateral
neurosensory detachment with final visual acuity of 0.6 for the right eye and 0.1
for the left one. DISCUSSION: The new therapeutic strategies against metastatic
cutaneous melanoma condition the appearance of alterations of the pigmentary
epithelium of the retina with serous detachments, leading to close monitoring
with macular optical coherence tomography.
PMID- 28506717
TI - Torpedo maculopathy with serous detachment of retinal pigment epithelium.
PMID- 28506715
TI - Geographic and population-level disparities in colorectal cancer testing: A
multilevel analysis of Medicaid and commercial claims data.
AB - Morbidity and mortality from colorectal cancer (CRC) can be attenuated through
guideline concordant screening and intervention. This study used Medicaid and
commercial claims data to examine individual and geographic factors associated
with CRC testing rates in one state (Oregon). A total of 64,711 beneficiaries
(4516 Medicaid; 60,195 Commercial) became newly age-eligible for CRC screening
and met inclusion criteria (e.g., continuously enrolled, no prior history) during
the study period (January 2010-December 2013). We estimated multilevel models to
examine predictors for CRC testing, including individual (e.g., gender,
insurance, rurality, access to care, distance to endoscopy facility) and
geographic factors at the county level (e.g., poverty, uninsurance). Despite
insurance coverage, only two out of five (42%) beneficiaries had evidence of CRC
testing during the four year study window. CRC testing varied from 22.4% to 46.8%
across Oregon's 36 counties; counties with higher levels of socioeconomic
deprivation had lower levels of testing. After controlling for age, beneficiaries
had greater odds of receiving CRC testing if they were female (OR 1.04, 95% CI
1.01-1.08), commercially insured, or urban residents (OR 1.14, 95% CI 1.07-1.21).
Accessing primary care (OR 2.47, 95% CI 2.37-2.57), but not distance to endoscopy
(OR 0.98, 95% CI 0.92-1.03) was associated with testing. CRC testing in newly age
eligible Medicaid and commercial members remains markedly low. Disparities exist
by gender, geographic residence, insurance coverage, and access to primary care.
Work remains to increase CRC testing to acceptable levels, and to select and
implement interventions targeting the counties and populations in greatest need.
PMID- 28506718
TI - G-Quadruplex surveillance in BCL-2 gene: a promising therapeutic intervention in
cancer treatment.
AB - Recently, therapeutic implications of BCL-2 quadruplex invigorated the field of
clinical oncology. This Keynote review discusses how a BCL-2 quadruplex-selective
approach circumvents the limitations of existing therapeutics; and which
improvisations might ameliorate the recent trends of quadruplex-based treatment.
PMID- 28506719
TI - Two fatalities associated with synthetic opioids: AH-7921 and MT-45.
AB - In this study, two fatalities associated with the synthetic opioids AH-7921 and
MT-45 are reported. Within the last few years, both compounds have emerged on the
recreational drug market and are sold as "research chemicals" on the internet. In
the first case, a 22-year-old woman was found dead in the bedroom of her
apartment by two of her friends. A plastic bag labeled "AH-7921" was found in the
apartment and the two friends stated that the deceased had consumed AH-7921 prior
to her death. The woman was a known drug addict. In the second case, a 24-year
old man was found dead in his room by his mother. The deceased was sitting on a
chair in front of his desk slumped over. Several bags of white powder labeled "MT
45", "Methoxmetamine" and "Methoxphenidine" were found in his room. Toxicological
analyses of femoral blood, heart blood, liver, pericardial fluid, urine, vitreous
humor and stomach content of the deceased were performed using liquid
chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS). Time-of
flight mass spectrometry was carried out on an LC-Triple TOF 5600 system (AB
Sciex) with electrospray ionization operated in positive mode. In the first case,
additional hair analysis was performed by liquid chromatography-tandem mass
spectrometry (LC-MS/MS) and LC-QTOF-MS. In both cases, the relevant synthetic
opioid could be detected in all analyzed samples. The concentration of AH-7921
was determined to be 450MUg/L in femoral blood. MT-45 was present at a
concentration of 2900MUg/L in femoral blood. Besides methoxmetamine which could
qualitatively be detected in femoral blood, urine and stomach content no
methoxphenidine was found. In summary, deaths of the young individuals could be,
by exclusion of other causes of death, attributed to the consumption of an
overdose of AH-7921 and MT-45, respectively.
PMID- 28506720
TI - Sunlight-activated near-infrared phosphorescence as a viable means of latent
fingermark visualisation.
AB - The chromium-doped zinc gallogermanate, Zn3Ga2Ge2O10:0.5%Cr3+, was prepared and
modified for use as a near-infrared (NIR) luminescent fingerprint dusting powder.
The optical properties of this material are illustrated and have been shown to
offer versatility and promise in terms of overcoming troublesome backgrounds
during latent fingermark examination and imaging. The highly fluorescent NIR
emission of the powder allows inherently fluorescent and patterned substrate
backgrounds to be mitigated, whilst the phosphorescent nature of the material
allows all conceivable background interference to be removed, whilst also
constituting the first reported use of a NIR phosphor for latent fingermark
enhancement and imaging.
PMID- 28506721
TI - First report of NDM-1-producing clinical isolate of Leclercia adecarboxylata in
Spain.
AB - We describe the case of NDM-1-producing Leclercia adecarboxylata recovered from
the clinical sample of a patient hospitalized for a trauma-related injury to his
foot. The isolate was resistant to all beta-lactams, quinolones, trimetroprim
sulfametoxazol, gentamicin and tobramicyn. The blaNDM-1 gene was located in a
conjugative plasmid that also contained the blaSHV-12 gene and was preceded by a
disrupted insertion sequence of ISAba125. The plasmid belongs to the
incompatibility group X3, which is known to be an important vector for NDM-1
dissemination in China. This is the first reported case of NDM-1L. adecarboxylata
in our country and evidences that species of uncertain clinical relevance can act
as hidden sources of clinically important resistance determinants.
PMID- 28506722
TI - Primary Helicobacter pylori resistance in elderly patients over 20 years: A
Bulgarian study.
AB - We evaluated the antibiotic susceptibility of 233 Helicobacter pylori strains
isolated in the period 2011-2016, involving 62 strains from elderly patients aged
66-93years and 171 strains from younger adults. To assess resistance evolution,
primary resistance rates in 92 strains from as many patients aged >=60years in
1996-2003 were compared with those in 85 strains from infected patients in the
same age group in 2011-2016. In the patients aged >65years evaluated during the
last 6 years, amoxicillin resistance according to EUCAST and prior breakpoints
was 1.6 and 0%, respectively. Resistance rates were the same by both breakpoint
systems to metronidazole (35.5%), clarithromycin (22.6%), tetracycline (1.6%) and
levofloxacin (32.3%). In 2011-2016, there were no significant differences between
resistance rates in the subjects aged >65years and the younger adults. Notably,
during the last 6 years, double/triple resistance was found in 21.0% of the
subjects aged >65years. Moreover, the prevalence of quinolone primary resistance
(30.0%) was significantly (3.4-fold) higher than that (8.9%) observed in 1996
2003. Briefly, the presence of both combined resistance and a strikingly high
primary levofloxacin resistance in the elderly implies a cautious antibiotic
choice for H. pylori eradication. In vitro susceptibility testing of the strains
is highly important in this age group. The results can be linked to more frequent
comorbidities and co-infection treatment in older compared with younger patients
and, additionally, to the national antibiotic consumption. The high prevalence of
quinolone resistance in the elderly patients is an alarming finding.
PMID- 28506723
TI - A chronicle of surgical thinking and doing for exotropia: innovations and
rediscoveries.
AB - PURPOSE: To review the evolution of theories and practices concerning surgery for
exotropia over the last approximately 200 years. METHODS: Major ophthalmology
texts and relevant references were reviewed to discover experience and thinking
concerning the causes of comitant intermittent and constant exotropia and
corrective surgical approaches. RESULTS: The concept that excessive divergence is
the cause of comitant exotropia has given way to one recognizing that this
disorder is a position of rest modified by convergence. Some operations discarded
as unreliable or dangerous remain so today. Others continue to be well accepted,
whether or not relating to advances in understanding of this condition. Several
procedures practiced at former times have regained popularity. CONCLUSIONS:
Concern for the characteristics of extraocular muscle structure and function has
led to surgical thinking that goes beyond consideration only of direction and
magnitude of deviation. Sophisticated devices now provide heretofore unavailable
information consistent with this new approach. The history of progress in surgery
for exotropia is mixed. Although some procedures now employed are new, others
currently in favor had been well known and formerly utilized by ophthalmologists
for many decades. These should be regarded as rediscoveries or revivals rather
than as novel. This review also suggests a need to address how to better report
retrospective studies.
PMID- 28506724
TI - Validation of WINROP for detecting retinopathy of prematurity in a North American
cohort of preterm infants.
AB - BACKGROUND: WINROP (weight, insulin-like growth factor 1, neonatal, retinopathy
of prematurity) is a web-based retinopathy of prematurity (ROP) risk algorithm
that uses postnatal weight gain as a surrogate of insulin-like growth factor-1
(IGF-1) to predict the risk of severe ROP in premature infants. The purpose of
this study was to validate the web-based algorithm WINROP in detecting severe
(type 1 or type 2) ROP in a North American cohort of infants. METHODS: The
records of consecutive infants who underwent ROP examinations between 2008 and
2011 were reviewed retrospectively. Infants were classified into categories of
"alarm" (at risk for developing severe ROP) and "no alarm" (minimal risk for
severe ROP). RESULTS: A total of 483 were included. Alarm occurred in 241
neonates (50%), with the median time from birth to alarm of 2 weeks. WINROP had a
sensitivity of 81.8% (95% CI, 67.3%-91.8%) and specificity of 53.3% (95% CI,
48.5%-58.0%) for identifying infants with severe ROP. Eight of the 44 infants
with severe ROP were not detected (5 with type 1 and 3 with type 2). Of these 8
infants, 7 (88%) had birth weight in excess of the 70th pecentile. With
additional weight data entry, sensitivity of WINROP rose to 88.6%. CONCLUSIONS:
Very preterm infants (gestational age of <=27 weeks) with relatively high birth
weight for gestational age may not be detected by WINROP as high risk for
developing severe ROP.
PMID- 28506725
TI - The first invertebrate NFIL3 transcription factor with role in immune defense
identified from the Hong Kong oyster, Crassostrea hongkongensis.
AB - NFIL3 (nuclear factor interleukin 3-regulated) is a basic leucine zipper type
transcription factor that mediates a variety of immune responses in vertebrates.
However, the sequence information and function of NFIL3 homologs in
invertebrates, especially mollusks, remains unknown. In the present study, the
first NFIL3 homolog was identified in a marine mollusk, Crassostrea hongkongensis
(designated as ChNFIL3), followed by its functional characterization. The full
length cDNA of ChNFIL3 is 2221 bp and consists of an open reading frame (ORF) of
1536 bp that encodes a polypeptide of 551 amino acids. Simple Modular
Architecture Research Tool (SMART) analysis indicated that ChNFIL3 has two basic
leucin zipper domains, similar to the other known NFIL3 family proteins. Tissue
distribution analysis of NFIL3 in this mollusk revealed high expression in
digestive glands and hemocytes. A significant induction in the mRNA level of
ChNFIL3 was observed following bacterial stimulation. ChNFIL3 was found to be
localized in the nucleus and over expression of ChNIFL3 led to upregulation of
transcriptional activity of an NF-kappaB reporter gene in HEK 293T cells,
indicating its role in innate immunity. Furthermore, addition of exogenous
recombinant ChNFIL3 proteins resulted in enhanced mRNA level of hemocyte
interleukin 17 in vitro. In conclusion, our findings revealed that NFIL3 in
molluscs, plays a conserved role in host defense, similar to its mammalian
homolog.
PMID- 28506726
TI - Influence of xanthan, guar, CMC and gum acacia on functional properties of water
chestnut (Trapa bispinosa) starch.
AB - This study was performed to determine the effect of xanthan, guar, CMC and gum
acacia on functional and pasting properties of starch isolated from water
chestnut (Trapa bispinosa). Morphological properties of water chestnut starch
with CMC were studied by scanning electron microscopy (SEM). The addition of
hydrocolloids significantly enhanced the solubility of water chestnut starch
(WCS) while reduced swelling power and freeze-thaw stability. The hydrophilic
tendency of WCS was increased by xanthan gum; however, with addition of gum
acacia it decreased significantly. Starch was modified with guar and gum acacia
exhibited highest% syneresis. Guar gum was found to be effective in increasing
the clarity of water chestnut starch paste. The addition of CMC significantly
reduced the pasting temperature of WCS indicating ease of gelatinization. The
setback was accelerated in the presence of xanthan gum but gum acacia delayed
this effect during the cooling of the starch paste. Only xanthan gum was found to
be effective in increasing breakdown showing good paste stability of WCS.
PMID- 28506727
TI - [Differences and similarities between occupational and tobacco induced COPD].
AB - Chronic obstructive pulmonary disease (COPD) most often results from the
inhalation of toxic agents. Cigarette smoking still remains the principal cause
but the pertinence of occupational COPD is now clearly established. After a brief
overview of the epidemiology of this "other COPD", the clinical and functional
characteristics are summarized, taking into account recent advances in this
field. The combined effects of occupational exposure and tobacco are also
considered, providing evidence of the need to continuously reinforce campaigns of
education and prevention in occupational COPD.
PMID- 28506728
TI - [The effects of inhaled steroids withdrawal in COPD].
AB - The key pathophysiological feature of chronic obstructive pulmonary disease
(COPD) is an abnormal inflammatory bronchial reaction after inhalation of toxic
substances. The priority is the avoidance of such toxic inhalations, but the use
of anti-inflammatory drugs also seems appropriate, especially corticosteroids
that are the sole anti-inflammatory drug available for this purpose in France.
The risks associated with the prolonged use of these parenteral drugs are well
known. Inhalation is therefore the optimal route, but inhaled drugs may also lead
to adverse consequences. In COPD, there is an inhaled corticosteroids overuse,
and a non-satisfactory respect of the guidelines. Consequently, their withdrawal
should be considered. We reviewed seven clinical studies dealing with inhaled
corticosteroids withdrawal in patients with COPD and found that included
populations were heterogenous with different concomitant treatments. In non
frequent exacerbators receiving inhaled corticosteroids outside the
recommendations, withdrawal appears to be safe under a well-managed
bronchodilator treatment. In patients with severe COPD and frequent
exacerbations, the risk of acute respiratory event is low when they receive
concomitant optimal inhaled bronchodilators. However, other risks may be observed
(declining lung function, quality of life) and a discussion of each case should
be performed, especially in case of COPD and asthma overlap.
PMID- 28506729
TI - [The role of extracorporeal removal of CO2 (ECCO2R) in the management of
respiratory diseases].
AB - INTRODUCTION: The aim of extracorporeal removal of CO2 (ECCO2R) is to ensure the
removal of CO2 without any significant effect on oxygenation. ECCO2R makes use of
low to moderate extracorporeal blood flow rates, whereas extracorporeal membrane
oxygenation (ECMO) requires high blood flows. STATE OF THE ART: For each ECCO2R
device it is important to consider not only performance in terms of CO2 removal,
but also cost and safety, including the incidence of hemolysis and of hemorrhagic
and thrombotic complications. In addition, it is possible that the benefits of
such techniques may extend beyond simple removal of CO2. There have been
preliminary reports of benefits in terms of reduced respiratory muscle workload.
Mobilization of endothelial progenitor cells could also occur, in analogy to the
data reported with ECMO, with a potential benefit in term of pulmonary repair.
The most convincing clinical experience has been reported in the context of the
acute respiratory distress syndrome (ARDS) and severe acute exacerbations of
chronic obstructive pulmonary disease (COPD), especially in patients at high risk
of failure of non-invasive ventilation. PERSPECTIVES: Preliminary results prompt
the initiation of randomized controlled trials in these two main indications.
Finally, the development of these technologies opens new perspectives in terms of
long-term ventilatory support.
PMID- 28506730
TI - [The human gut microbiota: Interactions with the host and dysfunctions].
AB - The human intestinal microbiota is composed of approximately 100,000 billion
microorganisms with the average total number of different commensal bacterial
species estimated at over 500 per individual. The human intestinal microbiota can
be considered as an organ within another, which co-evolved with its host to
achieve a symbiotic relationship leading to physiological homeostasis. The host
provides an environment enriched in nutrients and the microbiota provides
essential functions. Dysbiosis of the intestinal microbiota (changes in bacterial
composition) has been associated with local dysfunctions of the gastrointestinal
tract, such as inflammatory bowel disease or irritable bowel syndrome but also
with obesity and metabolic diseases. However, a better understanding of the human
intestinal ecosystem is still needed to understand the exact role of the
microbiota in health and disease. Most intestinal bacteria are anaerobic and
therefore, for the large majority, impossible to culture at present.
Consequently, their function cannot be inferred from data on their composition.
Today, with the help of a metagenomic approach, the bacterial genomic content of
an ecosystem and the associated functions can be directly accessed from the
environment without culture.
PMID- 28506731
TI - Risk of Heart Failure in Obese Patients With and Without Bariatric Surgery in
Sweden-A Registry-Based Study.
AB - BACKGROUND: Obesity is a known risk factor for heart failure. The prevalence of
both conditions has increased in Sweden during the past several decades. Obesity
surgery has been shown to improve cardiac function. We therefore investigated
whether the risk of heart failure was lower in obese patients after bariatric
surgery compared with obese patients without surgical intervention. METHODS AND
RESULTS: From the Swedish National Patient Registry. we created a cohort
including 47,859 patients aged 18-74 years with a primary diagnosis of obesity
from 2000 to 2011. Of these, 22,295 (46.6%) underwent bariatric surgery (mean age
40.7 (standard deviation [SD] 10.7) years, 75.9% female). There were 25,564
(53.4%) nonsurgical obese patients (mean age 44.3 (SD 13.2) years, 66.8% female).
Patients who underwent bariatric surgery had a markedly reduced risk of heart
failure compared with nonsurgical obese patients (age- and sex-adjusted hazard
ratio [HR] 0.37, 95% confidence interval [CI] 0.29-0.46). The lower risk
persisted after further adjustment for baseline differences in known risk factors
for heart failure (HR 0.37, 95% CI 0.30-0.46). CONCLUSION: Patients who underwent
bariatric surgery had a reduced risk of heart failure after surgery compared with
nonsurgical obese patients.
PMID- 28506732
TI - Primary seminal vesicle carcinoma. The usefulness of PAX8 immunohistochemical
expression for the differential diagnosis.
AB - Primary seminal vesicle carcinoma is a rare entity whose diagnosis can be
achieved by ruling out the main carcinomas that commonly invade the seminal
vesicles. Although a panel of immunohistochemical markers (cancer antigen 125,
cytokeratin [CK] 7, CK20, prostate-specific antigen, and prostate-specific acid
phosphatase) has been proposed as unique for primary seminal vesicle carcinoma, a
reliable positive marker is lacking. In this article, we report a case of primary
seminal vesicle carcinoma in a 57-year-old man. The tumor was localized to the
left seminal vesicle and histologically characterized by papillae lined by broad
eosinophilic cells with pleomorphic nuclei. The neoplastic cells expressed cancer
antigen 125 and CK7, whereas CK20, prostate-specific antigen, and prostate
specific acid phosphatase were negative. A strong and diffuse nuclear labeling
for PAX8 was detected. Because carcinomas of the colon, bladder, and prostate,
the main differential diagnosis in this setting, have been reported consistently
to be PAX8 negative, this marker may be very useful for a prompt diagnosis of
seminal vesicle carcinoma.
PMID- 28506733
TI - Variant morphology in upper urinary tract urothelial carcinoma: a 14-year case
series of biopsy and resection specimens.
AB - Upper urinary tract urothelial carcinoma exhibiting variant morphology,
especially in higher-grade tumors, is a recognized phenomenon but has not been
comparatively studied in biopsy versus resection material. We studied the
morphologic patterns and clinicopathological features, and provide a comparison
between biopsy and resection specimens. Consultation cases were evaluated
separately to investigate for possible consultation bias. A total of 383 in-house
cases from 352 patients including 314 resection specimens and 69 biopsies from
2001 to 2014 were reviewed from a single institution. Histologic type, tumor
grade, invasion, pathologic stage, nodal status, metastasis, and the presence and
type of variant morphology for each case were evaluated. Variant morphology was
identified in 5 biopsy specimens (7.2%) and 42 resection specimens (13.4%). The
most common variant morphologic pattern was squamous differentiation (16 cases,
4.5%) followed by an inverted growth pattern (8 cases, 2.2%). The presence of
variant morphology in resection specimens had a significant association with
higher tumor grade, higher pT stage, and nonpapillary configuration. Of 69
patients with biopsies, 31 had a subsequent resection. In comparison, 181
consultation cases from 168 patients showed variant morphology in 6 biopsies
(7.1%) and 27 resections (28.1%). In conclusion, the frequency of recognizing
variant morphology in biopsies is about one-half of that in resections. The
inclusion of consultation cases can inflate the incidence of variant morphology.
As a result, the frequency of variant morphology in our in-house cases is lower
than the percentage reported in the literature, most likely secondary to a
consultation bias.
PMID- 28506736
TI - Editorial Comment.
PMID- 28506734
TI - mTOR, VEGF, PDGFR, and c-kit signaling pathway activation in Kaposi sarcoma.
AB - Kaposi sarcoma (KS) is a locally progressive, intermediate-grade vascular
neoplasm with no known cure, high recurrence rates, and potential for wide
dissemination. Low efficacy and high toxicity limit current therapeutic options
for advanced disease. Activation of mammalian target of rapamycin (mTOR),
platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF),
and c-kit signaling pathways has been implicated in KS pathogenesis and may
suggest a role for targeted inhibitors. KS cases were retrospectively retrieved
(N=274), most (90%) associated with human immunodeficiency virus. Tissue
microarray slides were stained with human herpes virus-8, Friend leukemia
integration 1 transcription factor, CD117 (c-kit), phospho-S6 (pS6), PDGF
receptor-beta, VEGF, and phospho-mTOR. Both intensity and extent of staining were
scored. Multiplying these scores for each core yielded total staining H-scores.
Human herpes virus-8 was positive in 87% and Friend leukemia integration 1
transcription factor in 95.7% of cases. Most were also VEGF+ (97.6%), pS6+
(95.7%), CD117+ (92.5%), and PDGFRB+ (87.4%). Approximately half (55.6%) were
phospho-mTOR+. There was no significant difference in staining among patients
with low (<500 cells/mm3) or preserved CD4 T-cell counts. Immunohistochemistry
confirms upregulation of the mTOR, PDGF, VEGF, and c-kit pathways in a large
cohort of KS samples. Of proteins tested, pS6, downstream of mTOR, demonstrated
the highest proportion of strong positivity (67.1%). These results support the
possibility of using targeted inhibitors in KS. Overexpression was independent of
CD4 count, suggesting that even patients with low counts may be targeted therapy
candidates.
PMID- 28506735
TI - A proposal for standardization of transgenic reference sequences used in food
forensics.
PMID- 28506737
TI - Detection of genital chlamydial and gonococcal infection using urine samples: A
community-based study from India.
AB - Sexually transmitted infections (STI) have a major impact on the reproductive
health of women. Among the different etiological agents of STIs, Chlamydia
trachomatis and Neisseria gonorrhoeae are the main bacterial pathogens that cause
sexually transmitted infections in women. The aim of the study was to estimate
the prevalence of genital chlamydial and gonococcal infection among women in the
age group of 18-65 years from a community-based setting. A community-based cross
sectional study was performed using the archived urine samples (n=811) of women
in the age group of 18-65 years for C. trachomatis and N. gonorrhoeae using a
multiplex conventional Polymerase Chain Reaction (PCR). Out of 811 samples tested
in the present study, 2 (0.24%) were tested positive for C. trachomatis and none
were positive for N. gonorrhoeae. The study demonstrates the very low prevalence
of C. trachomatis and N. gonorrhoeae infection in a rural community. For large
population-based screening, urine samples were observed to be more socially
acceptable and cost-effective.
PMID- 28506738
TI - [Mental disorders and their underdiagnosis in primary care].
AB - : Despite its high prevalence, mental disorders are often underdiagnosed.
OBJECTIVE: To determine the magnitude of the underdiagnosis mental disorders and
its associated characteristics. METHODOLOGY: A descriptive cross-sectional study
performed in Lanzarote (2011) on 310 patients selected by cluster random
sampling. A self-completed questionnaire was used that contained the General
Health Questionnaire-28, as well as structured interview using the Mini
International Neuropsychiatric Interview to confirm the diagnosis of mental
disorder. The current diagnosis registered in the DRAGO-AP electronic medical
record was also recorded. RESULTS: Of the 75 patients detected with the
interview, 14 (18.67%) had a diagnosis recorded in the medical record
(sensitivity=0.19; IC 95% CI; 0.09-28). The positive predictive value of being in
the medical record was 0.56. With respect to sensitivity, only the "number of
visits made to the health centre in the last 3 months" was significantly higher
in the group of patients also with a diagnosis of any mental disorder in the
medical record (5 vs. 2.77; p=.002). CONCLUSIONS: There is an important
underdiagnosis of the mental disorders in our environment. More visits to the
health centre are associated with this diagnosis.
PMID- 28506739
TI - [Hyperglycaemia as an unusual manifestation of small cell lung carcinoma with
ectopic adrenocorticotropic hormone secretion].
PMID- 28506740
TI - [Cause of acute non-surgical abdomen: omental infarction].
PMID- 28506741
TI - Evaluation of a sound environment intervention in an ICU: A feasibility study.
AB - BACKGROUND: Currently, it is well known that the sound environment in intensive
care units (ICU) is substandard. Therefore, there is a need of interventions
investigating possible improvements. Unfortunately, there are many challenges to
consider in the design and performance of clinical intervention studies including
sound measurements and clinical outcomes. OBJECTIVES: (1) explore whether it is
possible to implement a full-scale intervention study in the ICU concerning sound
levels and their impact on the development of ICU delirium; (2) discuss
methodological challenges and solutions for the forthcoming study; (3) conduct an
analysis of the presence of ICU delirium in the study group; and (4) describe the
sound pattern in the intervention rooms. METHODS: A quasi-randomized clinical
trial design was chosen. The intervention consisted of a refurbished two-bed ICU
patient room (experimental) with a new suspended wall-to-wall ceiling and a low
frequency absorber. An identical two-bed room (control) remained unchanged.
INCLUSION CRITERIA: Patients >18 years old with ICU lengths of stay (LoS) >48h.
The final study group consisted of 31 patients: six from the rebuilt experimental
room and 25 from the control room. Methodological problems and possible solutions
were continuously identified and documented. RESULTS: Undertaking a full-scale
intervention study with continuous measurements of acoustic data in an ICU is
possible. However, this feasibility study demonstrated some aspects to consider
before start. The randomization process and the sound measurement procedure must
be developed. Furthermore, proper education and training are needed for
determining ICU delirium. CONCLUSION: This study raises a number of points that
may be helpful for future complex interventions in an ICU. For a full-scale study
to be completed a continuously updated cost calculation is necessary.
Furthermore, representatives from the clinic need to be involved in all stages
during the project.
PMID- 28506742
TI - Investigation of gene expression and serum levels of PIN1 and eNOS with high
blood pressure in patients with Alzheimer disease.
AB - According to evidence, Alzheimer's disease is known as one of the most serious
neurodegenerative diseases, for which hypertension has been observed to be a key
risk factor. Therefore, this study aims to examine the relationship between the
PIN1 and eNOS genes expression, as well as serum levels and hypertension in
Alzheimer's disease sufferers. Blood samples were obtained from subjects who were
divided into four groups: the control group, normotensive Alzheimer's patients,
the Alzheimer's sufferers group with hypertension, and the healthy group with
only hypertension, considering the inhibition of confounding factors. Thereafter,
eNOS and PIN1 genes expression along with serum levels were studied. Based on the
obtained results, a statistically significant correlation didn't exist between
serum level of PIN1 and the systolic and diastolic blood pressure, between serum
level of eNOS and diastolic blood pressure in the norm tension Alzheimer's
disease patients, between serum levels of PIN1, eNOS and systolic blood pressure,
and between serum eNOS and systolic and diastolic blood pressure in the patients
with hypertension (p<0.05). According to the results obtained from this study,
measuring the serum levels of eNOS and Pin1 may contribute to the prognosis,
prevention, and monitoring of hypertension and also to the reduction of death
rates from cardiovascular diseases in Alzheimer's disease.
PMID- 28506743
TI - Peptide ligand-modified nanomedicines for targeting cells at the tumor
microenvironment.
AB - Since their initial discovery more than 30years ago, tumor-homing peptides have
become an increasingly useful tool for targeted delivery of therapeutic and
diagnostic agents into tumors. Today, it is well accepted that cells at the tumor
microenvironment (TME) contribute in many ways to cancer development and
progression. Tumor-homing peptide-decorated nanomedicines can interact
specifically with surface receptors expressed on cells in the TME, improve
cellular uptake of nanomedicines by target cells, and impair tumor growth and
progression. Moreover, peptide ligand-modified nanomedicines can potentially
accumulate in the target tissue at higher concentrations than would small
conjugates, thus increasing overall target tissue exposure to the therapeutic
agent, enhance therapeutic efficacy and reduce side effects. This review
describes the most studied peptide ligands aimed at targeting cells in the TME,
discusses major obstacles and principles in the design of ligands for drug
targeting and provides an overview of homing peptides in ligand-targeted
nanomedicines that are currently in development for cancer therapy and diagnosis.
PMID- 28506746
TI - The NAD+-dependent deacetylase, Bifidobacterium longum Sir2 in response to
oxidative stress by deacetylating SigH (sigmaH) and FOXO3a in Bifidobacterium
longum and HEK293T cell respectively.
AB - Silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent
protein/histone deacetylation. The mammalian sirtuin family SIRT1, SIRT2, SIRT3
and SIRT6 can regulate oxidative stress. The probiotics (Bifidobacterium
longum(B.longum) and Lactobacillus acidophilus(L. acidophilus)) have Sir2 gene
family and have antioxidant activity in human body. it remains unknown whether
probiotics Sir2 has a direct role in regulating oxidative stress. To this end, we
knockout BL-sir2(sir2 B. longum) and LA-sir2(sir2 L.acidophilus) in low oxygen
level. The antioxidant activities of two sir2 deficient strains was decreased,
while when reintroduction of BL-sir2 and LA-sir2, the antioxidant activities were
recoveried. In order to understand the regulation mechanism of probiotics Sir2
oxidation response. Then, we screened 65 acetylated protein, and found that SigH
(sigmaH) was a substrate of BL-Sir2. In addition, the acetylation level of sigmaH
decreased with the increase of BL-Sir2 level in B. longum. Thus, BL-Sir2
deacetylated sigmaH in response to oxidative stress. Next, we transfected BL-Sir2
into H2O2-induced oxidative damage of 293T cells, BL-Sir2 increased the activity
of manganese superoxide dismutase (MnSOD/SOD2) and catalase (CAT) and reduced
reactive oxygen species(ROS). Then, we analyzed the differential gene by RNA
sequencing and Gene ontology (GO) and found that BL-Sir2 regulated forkhead
transcription factor (FOXO3a) mediated antioxidant genes in overexpressed BL-Sir2
HEK293T cells. Our study is the first to link probiotics Sir2 with oxidative
stress and uncover the antioxidant mechanism of BL-Sir2 in B. longum itself and
human body.
PMID- 28506747
TI - Reply.
PMID- 28506748
TI - Copy number variation analysis of patients with intellectual disability from
North-West Spain.
AB - Intellectual disability (ID) is a complex and phenotypically heterogeneous
neurodevelopmental disorder characterized by significant deficits in cognitive
and adaptive skills, debuting during the developmental period. In the last
decade, microarray-based copy number variation (CNV) analysis has been proved as
a strategy particularly useful in the discovery of loci and candidate genes
associated with these phenotypes and is widely used in the clinics with a
diagnostic purpose. In this study, we evaluated the usefulness of two genome-wide
high density SNP microarrays -Cytogenetics Whole-Genome 2.7M SNP array (n=126
patients; Group 1) and CytoScan High-Density SNP array (n=447 patients; Group 2)-
in the detection of clinically relevant CNVs in a cohort of ID patients from
Galicia (NW Spain). In 159 (27.7%) patients, we detected 186 rare exonic
chromosomal imbalances, that were grouped into the following classes: Clinically
relevant (67/186; 36.0%), of unknown clinical significance (93/186; 50.0%) and
benign (26/186; 14.0%). The 67 pathogenic CNVs were identified in 64 patients,
which means an overall diagnostic yield of 11.2%. Overall, we confirmed that ID
is a genetically heterogeneous condition and emphasized the importance of using
genome-wide high density SNP microarrays in the detection of its genetic causes.
Additionally, we provided clinical and molecular data of patients with pathogenic
or likely pathogenic CNVs and discussed the potential implication in
neurodevelopmental disorders of genes located within these variants.
PMID- 28506749
TI - Minority College Students' HPV Knowledge, Awareness, and Vaccination History.
PMID- 28506750
TI - Cytotoxic and apoptosis-inducing activities against human lung cancer cell lines
of cassaine diterpenoids from the bark of Erythrophleum fordii.
AB - A phytochemical investigation into the bark of Erythrophleum fordii yielded four
new compounds, two new cassaine diterpenoids (erythrofordin T and U, 1 and 2) and
two new cassaine diterpenoid amines (erythroformine A and B, 6 and 7), as well as
nine known compounds. We report for the first time the isolation of erythrofordin
V (3) from a natural source and that of the remaining eight known diterpenoids (4
5, 8-13) from E. fordii. All structures were elucidated using spectroscopic
analysis. Cytotoxic activity of the isolated compounds (1-13) was examined in
vitro against three non-small cell lung cancer cell lines (A549, NCI-H1975, and
NCI-H1229) using the MTT assay. Cassaine diterpene amines (6-10, 12, 13)
exhibited potent cytotoxic activity against all three cell lines with IC50 values
between 0.4MUM and 5.9MUM. Erythroformine B (7) significantly induced apoptosis
in all three cancer cells in a concentration-dependent manner.
PMID- 28506751
TI - Recent progress towards clinically relevant ATP-competitive Akt inhibitors.
AB - The frequency of PI3K/Akt/mTOR (PAM) Pathway mutations in human cancers sparked
interest to determine if the pathway is druggable. The modest clinical benefit
observed with mTOR rapalogs (temsirolimus and everolimus) provided further
motivation to identify additional nodes of pathway inhibition that lead to
improved clinical benefit. Akt is a central signaling node of the PAM pathway and
could be an ideal target for improved pathway inhibition. Furthermore, inhibitors
of Akt may be especially beneficial in tumors with Akt1 mutations. Recently,
multiple ATP-competitive Akt inhibitors have been identified and are currently in
clinical development. This review details the medicinal chemistry efforts towards
identification of these molecules, highlights relevant preclinical data
supporting clinical evaluation, and summarizes current clinical development
plans.
PMID- 28506752
TI - Thio-functionalized carbohydrate thiosemicarbazones and evaluation of their
anticancer activity.
AB - Thiosemicarbazides and their analogs have shown potential medical applications as
antiviral, antibacterial and anticancer drugs. We designed, synthesized and
evaluated in vitro anticancer activity against ovarian (A2780), cervix (HeLa),
colon (LoVo), breast (MCF-7) and brain (MO59J) human cancer cell lines of seven
novel compounds -S-glycosylated thiosemicarbazones. We assessed the cyto- and
genotoxic properties of all novel compounds using a variety of methods including
comet assay, XTT assay, various fluorescent assays and toxicology PathwayFinder
expression array. We tried to evaluate their possible mechanism of action with
particular attention to induction of DNA damage and repair, apoptosis, oxidative
stress analysis and cellular response in terms of changes in gene expression. The
most sensitive cell line was human ovarian cancer. The results revealed that the
major activity against A2780 cancer cell line displayed by our compounds is
induction of DNA damage. This effect is not associated with apoptosis or
oxidative stress induction and the resulting damage will not lead to cell cycle
arrest. We also observed up-expression of heat shock related genes and NQO1 gene
in response to our compounds. The second effect seems to be specific to
glycosylated S-bond compounds as we observed it earlier. Upregulation of heat
shock protein encoding genes suggest that our compounds induce stressful
conditions. The nature of this phenomena (heat shock, pH shift or hypoxia) needs
further study.
PMID- 28506745
TI - Applying nanomedicine in maladaptive inflammation and angiogenesis.
AB - Inflammation and angiogenesis drive the development and progression of multiple
devastating diseases such as atherosclerosis, cancer, rheumatoid arthritis, and
inflammatory bowel disease. Though these diseases have very different phenotypic
consequences, they possess several common pathophysiological features in which
monocyte recruitment, macrophage polarization, and enhanced vascular permeability
play critical roles. Thus, developing rational targeting strategies tailored to
the different stages of the journey of monocytes, from bone marrow to local
lesions, and their extravasation from the vasculature in diseased tissues will
advance nanomedicine. The integration of in vivo imaging uniquely allows studying
nanoparticle kinetics, accumulation, clearance, and biological activity, at
levels ranging from subcellular to an entire organism, and will shed light on the
fate of intravenously administered nanomedicines. We anticipate that convergence
of nanomedicines, biomedical engineering, and life sciences will help to advance
clinically relevant therapeutics and diagnostic agents for patients with chronic
inflammatory diseases.
PMID- 28506753
TI - Phenylbenzenesulfonates and -sulfonamides as 17beta-hydroxysteroid dehydrogenase
type 2 inhibitors: Synthesis and SAR-analysis.
AB - 17beta-Hydroxysteroid dehydrogenase type 2 (17beta-HSD2) converts the potent
estrogen estradiol into the weakly active keto form estrone. Because of its
expression in bone, inhibition of 17beta-HSD2 provides an attractive strategy for
the treatment of osteoporosis, a condition that is often caused by a decrease of
the active sex steroids. Currently, there are no drugs on the market targeting
17beta-HSD2, but in multiple studies, synthesis and biological evaluation of
promising 17beta-HSD2 inhibitors have been reported. Our previous work led to the
identification of phenylbenzenesulfonamides and -sulfonates as new 17beta-HSD2
inhibitors by ligand-based pharmacophore modeling and virtual screening. In this
study, new molecules representing this scaffold were synthesized and tested in
vitro for their 17beta-HSD2 activity to derive more profound structure-activity
relationship rules.
PMID- 28506754
TI - Synthesis, biological evaluation and molecular docking studies of chromone
hydrazone derivatives as alpha-glucosidase inhibitors.
AB - A series of chromone hydrazone derivatives 4a-4p have been synthesized,
characterized by 1H NMR and 13C NMR and evaluated for theirinvitro alpha
glucosidase inhibitory activity. Out of these tested compounds, six (4a, 4b, 4d,
4j, 4o and 4p) displayed potent alpha-glucosidase inhibitory activity with IC50
values in the range of 20.1+/-0.19MUM to 45.7+/-0.23MUM, as compared to the
standard drug acarbose (IC50=817.38+/-6.27MUM). Among this series, compound 4d
(IC50=20.1+/-0.19MUM) with 4-sulfonamide substitution at phenyl part of hydrazide
was found to be the most active compound. Lineweaver-Burk plot analysis indicated
that compound 4d is a non-competitive inhibitor of alpha-glucosidase. The binding
interactions of the most active analogs were confirmed through molecular docking
studies. Docking studies showed 4d are interacting with the residues Glu-276, Asp
214, Asp-349 and Arg-439 through hydrogen bonds, arene-anion and arene-cation
interactions. In summary, our studies shown that these chromone hydrazone
derivatives are a new class of alpha-glucosidase inhibitors.
PMID- 28506744
TI - Hepatic stellate cells as key target in liver fibrosis.
AB - Progressive liver fibrosis, induced by chronic viral and metabolic disorders,
leads to more than one million deaths annually via development of cirrhosis,
although no antifibrotic therapy has been approved to date. Transdifferentiation
(or "activation") of hepatic stellate cells is the major cellular source of
matrix protein-secreting myofibroblasts, the major driver of liver fibrogenesis.
Paracrine signals from injured epithelial cells, fibrotic tissue
microenvironment, immune and systemic metabolic dysregulation, enteric dysbiosis,
and hepatitis viral products can directly or indirectly induce stellate cell
activation. Dysregulated intracellular signaling, epigenetic changes, and
cellular stress response represent candidate targets to deactivate stellate cells
by inducing reversion to inactivated state, cellular senescence, apoptosis,
and/or clearance by immune cells. Cell type- and target-specific pharmacological
intervention to therapeutically induce the deactivation will enable more
effective and less toxic precision antifibrotic therapies.
PMID- 28506755
TI - [Analysis of the quality of life in patients affected by scoliosis].
AB - OBJECTIVES: To assess the quality of life using the SRS 22 test in patients with
scoliosis of 20 or more degrees Cobb. MATERIAL AND METHODS: A prospective
descriptive study was conducted between April and May 2016 on patients with
scoliosis of at least 20 degrees Cobb and aged between 10 and 20 years. A record
was made of weight, height, body mass index, and the SR 22 specific quality of
life questionnaire for patients with scoliosis was completed. Patients were
divided into two groups for analysis: a) scoliosis between 20 and 29 degrees Cobb
(n=44); and b) scoliosis with a Cobb of 30 degrees or greater (n=32). RESULTS:
There were significant differences in the dimensions that assess pain, image self
perception, and satisfaction with treatment, being valued worse when the degree
of scoliosis Cobb is 30 degrees or higher. There were no significant differences
in function/activity or mental health. The overall score of the questionnaire was
also worse in the group with the highest degree of scoliosis. The weight, height,
and BMI showed no significant differences due to the varying degrees of
scoliosis. CONCLUSIONS: Scoliosis significantly affects the quality of life of
people who suffer it, and there is a negative correlation between the severity of
scoliosis measured by degrees Cobb and quality of life.
PMID- 28506756
TI - [Estimation of the population attributable fraction due to obesity in hospital
admissions for flu valued according to Body Mass Index (BMI) and CUN-BAE].
AB - INTRODUCTION: The obesity pandemic together with the influenza pandemic could
lead to a significant burden of disease. The body mass index (BMI) does not
discriminate obesity appropriately. The CUN-BAE has recently been used as an
estimate of body fatness for Caucasians, including BMI, gender, and age. The aim
of this study is to assess the population attributable fraction of hospital
admissions due to influenza, due to the body fatness measured with the BMI, and
the CUN-BAE. METHODS: A multicentre study was conducted using matched case
controls. Cases were hospital admissions with the influenza confirmed by the RT
PCR method between 2009 and 2011. The risk of hospital admission and the
population attribuible fraction were calculated using the BMI or the CUN-BAE for
each adiposity category in a conditional logical regression analysis adjusted for
confounding variables. The analyzes were estimated in the total sample, in
unvaccinated people, and those less than 65 years-old. RESULTS: A total of 472
hospitalised cases and 493 controls were included in the study. Compared to
normal weight, the aOR of influenza hospital admissions increases with each level
of BMI (aOR=1.26; 2.06 and 11.64) and CUN-BAE (aOR=2.78; 4.29; 5.43 and 15.18).
The population attributable fraction of influenza admissions using CUN-BAE is 3
times higher than that estimated with BMI (0,72 vs. 0,27), with the differences
found being similar the non-vaccinated and under 65 year-olds. CONCLUSION: The
BMI could be underestimating the burden of disease attributable to obesity in
individuals hospitalised with influenza. There needs to be an appropriate
assessment of the impact of obesity and vaccine recommendation criteria.
PMID- 28506757
TI - [Refractory iron deficiency anaemia].
PMID- 28506759
TI - Complement C1q is hydroxylated by collagen prolyl 4 hydroxylase and is sensitive
to off-target inhibition by prolyl hydroxylase domain inhibitors that stabilize
hypoxia-inducible factor.
AB - Complement C1q is part of the C1 macromolecular complex that mediates the
classical complement activation pathway: a major arm of innate immune defense.
C1q is composed of A, B, and C chains that require post-translational prolyl 4
hydroxylation of their N-terminal collagen-like domain to enable the formation of
the functional triple helical multimers. The prolyl 4-hydroxylase(s) that
hydroxylate C1q have not previously been identified. Recognized prolyl 4
hydroxylases include collagen prolyl-4-hydroxylases (CP4H) and the more recently
described prolyl hydroxylase domain (PHD) enzymes that act as oxygen sensors
regulating hypoxia-inducible factor (HIF). We show that several small-molecule
prolyl hydroxylase inhibitors that activate HIF also potently suppress C1q
secretion by human macrophages. However, reducing oxygenation to a level that
activates HIF does not compromise C1q hydroxylation. In vitro studies showed that
a C1q A chain peptide is not a substrate for PHD2 but is a substrate for CP4H1.
Circulating levels of C1q did not differ between wild-type mice or mice with
genetic deficits in PHD enzymes, but were reduced by prolyl hydroxylase
inhibitors. Thus, C1q is hydroxylated by CP4H, but not the structurally related
PHD hydroxylases. Hence, reduction of C1q levels may be an important off-target
side effect of small molecule PHD inhibitors developed as treatments for renal
anemia.
PMID- 28506758
TI - Decreased homodimerization and increased TIMP-1 complexation of uteroplacental
and uterine arterial matrix metalloproteinase-9 during hypertension-in-pregnancy.
AB - Preeclampsia is a complication of pregnancy manifested as hypertension-in
pregnancy (HTN-Preg) and often intrauterine growth restriction (IUGR). Placental
ischemia could be an initiating event, but the molecular mechanisms are unclear.
To test the hypothesis that dimerization of matrix metalloproteinases (MMPs)
plays a role in HTN-Preg and IUGR, the levels/activity of MMP-9, tissue inhibitor
of metalloproteinase (TIMP-1), and their dimerization forms were measured in the
placenta, uterus, and uterine artery of normal pregnant (Preg) rats and a rat
model of reduced uteroplacental perfusion pressure (RUPP). Consistent with our
previous report, blood pressure (BP) was higher, pup weight was lower, and
gelatin zymography showed different gelatinolytic activity for pro-MMP-9, MMP-9,
pro-MMP-2 and MMP-2 in RUPP vs Preg rats. Careful examination of the zymograms
showed additional bands at 200 and 135kDa. Western blots with MMP-9 antibody
suggested that the 200kDa band was a MMP-9 homodimer. Western blots with TIMP-1
antibody as well as reverse zymography suggested that the 135kDa band was a MMP
9/TIMP-1 complex. The protein levels and gelatinase activity of MMP-9 homodimer
were decreased while MMP-9/TIMP-1 complex was increased in placenta, uterus and
uterine artery of RUPP vs Preg rats. The epidermal growth factor (EGF) receptor
blocker erlotinib and protein kinase C (PKC) inhibitor bisindolylmaleimide
decreased MMP-9 homodimer and increased MMP-9/TIMP-1 complex in placenta, uterus
and uterine artery of Preg rats. EGF and the PKC activator phorbol-12,13
dibutyrate (PDBu) reversed the decreases in MMP-9 homodimer and the increases in
MMP-9/TIMP-1 complex in tissues of RUPP rats. Thus, the increased BP and
decreased pup weight in placental ischemia model of HTN-Preg are associated with
a decrease in MMP-9 homodimer and an increase in MMP-9/TIMP-1 complex in
placenta, uterus, and uterine artery, which together would cause a net decrease
in MMP-9 activity and reduce uteroplacental and vascular remodeling in the
setting of HTN-Preg and IUGR. Enhancing EGFR/PKC signaling may reverse the MMP-9
unfavorable dimerization patterns and thereby promote uteroplacental and vascular
remodeling in preeclampsia.
PMID- 28506761
TI - The decline in kidney function with chromium exposure is exacerbated with co
exposure to lead and cadmium.
AB - Environmental factors contribute significantly to the pathogenesis of chronic
kidney disease. However, these factors, and particularly the toxic effects of
heavy metals, have not been completely evaluated. Chromium is a widespread
industrial contaminant that has been linked to nephrotoxicity in animal and
occupational population studies. Nevertheless, its role in population renal
health and its potential interactions with other nephrotoxic metals, such as lead
and cadmium, remain unknown. We assessed the association between exposure to
chromium, lead, and cadmium with renal function using estimated glomerular
filtration rate (eGFR) in an analysis of 360 Taiwanese adults aged 19-84 years
from the National Nutrition and Health Survey in Taiwan (2005-2008). Doubling of
urinary chromium or lead decreased the eGFR by -5.99 mL/min/1.73 m2 (95%
confidence interval -9.70, -2.27) and -6.61 (-9.71, -3.51), respectively, after
adjusting for age, sex, body mass index, hypertension, diabetes, cigarette
smoking, sodium intake, education, urinary volume, and other metals. For those in
the highest tertile of cadmium exposure, the eGFR decreased by -12.68 mL/min/1.73
m2 (95% confidence interval -20.44, -4.93) and -11.22 mL/min/1.73 m2 (-17.01,
5.44), as urinary chromium or lead levels doubled, respectively. Thus, there is a
significant and independent association between chromium exposure and decreased
renal function. Furthermore, co-exposure to chromium with lead and cadmium is
potentially associated with additional decline in the glomerular filtration rate
in Taiwanese adults.
PMID- 28506760
TI - Patients double-seropositive for ANCA and anti-GBM antibodies have varied renal
survival, frequency of relapse, and outcomes compared to single-seropositive
patients.
AB - Co-presentation with both ANCA and anti-GBM antibodies is thought to be
relatively rare. Current studies of such 'double-positive' cases report small
numbers and variable outcomes. To study this further we retrospectively analyzed
clinical features and long-term outcomes of a large cohort of 568 contemporary
patients with ANCA-associated vasculitis, 41 patients with anti-GBM disease, and
37 double-positive patients with ANCA and anti-GBM disease from four European
centers. Double-positive patients shared characteristics of ANCA-associated
vasculitis (AAV), such as older age distribution and longer symptom duration
before diagnosis, and features of anti-GBM disease, such as severe renal disease
and high frequency of lung hemorrhage at presentation. Despite having more
evidence of chronic injury on renal biopsy compared to patients with anti-GBM
disease, double-positive patients had a greater tendency to recover from being
dialysis-dependent after treatment and had intermediate long-term renal survival
compared to the single-positive patients. However, overall patient survival was
similar in all three groups. Predictors of poor patient survival included
advanced age, severe renal failure, and lung hemorrhage at presentation. No
single-positive anti-GBM patients experienced disease relapse, whereas
approximately half of surviving patients with AAV and double-positive patients
had recurrent disease during a median follow-up of 4.8 years. Thus, double
positive patients have a truly hybrid disease phenotype, requiring aggressive
early treatment for anti-GBM disease, and careful long-term follow-up and
consideration for maintenance immunosuppression for AAV. Since double-positivity
appears common, further work is required to define the underlying mechanisms of
this association and define optimum treatment strategies.
PMID- 28506763
TI - Neonatal hyperoxia disrupts the intestinal barrier and impairs intestinal
function in rats.
AB - Animal studies have demonstrated that neonatal hyperoxia injures the distal small
intestine and disrupts the intestinal barrier. This study evaluated the effects
of brief hyperoxia exposure on intestinal function in newborn rats. Newborn
Sprague-Dawley rat pups were exposed to room air or normobaric hyperoxia (85% O2)
for 1week. The rats were euthanized on Postnatal Day 7, and their terminal ilea
and sera were collected for histological analyses and intestinal permeability
measurements, respectively. Bacterial translocation to the liver and spleen under
aerobic and anaerobic conditions was determined. The expression and localization
of epithelial injury markers [intestinal fatty acid binding protein (I-FABP)],
intestinal barrier proteins [occludin and zonula occludens (ZO)-1], and
inflammation biomarkers [Toll-like receptor 4 (TLR4) and nuclear factor-kappaB
(NF-kappaB)] were analyzed through immunofluorescence staining. The body weight
at birth was comparable between the two groups. On Postnatal Day 7, the rats in
the hyperoxic group exhibited significantly lower body weights, higher intestinal
injury scores, lower numbers of goblet cells, higher I-FABP expression, lower
occludin and ZO-1 expression, higher TLR4 and NF-kappaB expression, and higher
intestinal permeability and bacterial translocation than did those in the room
air group. The rats reared in O2-enriched air displayed indistinct tight junction
with widening of the paracellular spaces. Hyperoxia exposure injured the distal
small intestine, disrupted the intestinal barrier, and impaired intestinal
function in newborn rats. Hyperoxia-induced intestinal injury may be attributable
to increased activity of the TLR4/NF-kappaB pathway during the postnatal period.
PMID- 28506762
TI - The nuclear phosphatase SCP4 regulates FoxO transcription factors during muscle
wasting in chronic kidney disease.
AB - Chronic kidney disease (CKD) and related inflammatory responses stimulate protein
energy wasting, a complication causing loss of muscle mass. Primarily, muscle
wasting results from accelerated protein degradation via autophagic/lysosomal and
proteasomal pathways, but mechanisms regulating these proteolysis pathways remain
unclear. Since dephosphorylation of FoxOs regulates ubiquitin/proteasome protein
metabolism, we tested whether a novel nuclear phosphatase, the small C-terminal
domain phosphatase (SCP) 4, regulates FoxOs signaling and, in turn, muscle
wasting. In cultured mouse myoblast cells, SCP4 overexpression stimulated
proteolysis, while knockdown of SCP4 prevented the proteolysis stimulated by
inflammatory cytokines. SCP4 overexpression led to nuclear accumulation of
FoxO1/3a followed by increased expression of catabolic factors including
myostatin, Atrogin-1, and MuRF-1, and induction of lysosomal-mediated
proteolysis. Treatment of C2C12 myotubes with proinflammatory cytokines
stimulated SCP4 expression in an NF-kappaB-dependent manner. In skeletal muscle
of mice with CKD, SCP4 expression was up-regulated. Similarly, in skeletal muscle
of patients with CKD, SCP4 expression was significantly increased. Knockdown of
SCP4 significantly suppressed FoxO1/3a-mediated expression of Atrogin-1 and MuRF
1 and prevented muscle wasting in mice with CKD. Thus, SCP4 is a novel regulator
of FoxO transcription factors and promotes cellular proteolysis. Hence, targeting
SCP4 may prevent muscle wasting in CKD and possibly other catabolic conditions.
PMID- 28506764
TI - Specific localization of LC3B in autophagosome: A correlative labelling study
with nanoparticle in oral squamous cell carcinoma.
PMID- 28506765
TI - Augmenter of liver regeneration (ALR) exhibits a dual signaling impact on hepatic
acute-phase response.
AB - The acute-phase response (APR) is an inflammatory process triggered mainly by IL
6 in response to neoplasm, tissue injury, infection or inflammation. Signaling of
IL-6 is transduced by activating STAT3 which rapidly results in production of
acute-phase proteins (APPs) such as fibrinogen beta (FGB) and haptoglobin (HP).
Augmenter of liver regeneration (ALR), a hepatotrophic factor supporting liver
regeneration, was reported to be upregulated after liver damage. In this study we
analyzed the role of ALR for IL-6 signaling and APR. Thus, we investigated the
expression and release of APPs in human liver cells under conditions of increased
exogenous or endogenous ALR. HepG2 cells and ALR-reexpressing HepG2 cells were
treated with IL-6 in the presence or absence of exogenous ALR for different time
points. The mRNA expression and release of both FGB and HP were measured by RT
PCR and ELISA. We found that exogenously applied ALR attenuated the IL-6-induced
mRNA expression and protein secretion of both FGB and HP. In contrast, IL-6
stimulation in HepG2 cells which re-express ALR, revealed elevated APR shown by
increased mRNA expression and secretion of FGB and HP. Furthermore, we found that
ALR-mediated regulation of IL-6-induced APP production is accompanied by altered
STAT3 activity. While exogenous ALR reduced the IL-6-induced phosphorylation of
STAT3, endogenous ALR enhanced STAT3 activity in liver cells. In conclusion, ALR,
dependent on its localization, changes APR at least in part, by modifying STAT3
activation. This study shows a dual signaling of ALR and suggests that ALR is
pivotal for the regulation of APR, a crucial event in liver injury and
regeneration.
PMID- 28506766
TI - Effects of microRNA-183 on epithelial-mesenchymal transition, proliferation,
migration, invasion and apoptosis in human pancreatic cancer SW1900 cells by
targeting MTA1.
AB - OBJECTIVE: This study aims to explore effects of miR-183 on epithelial
mesenchymal transition (EMT) and invasion by targeting MTA1 in human pancreatic
cancer (PC) cells. METHODS: Totally, 108 PC patients admitted in Wenzhou Central
Hospital and Wenzhou People's Hospital, The Dingli Clinical Institute of Wenzhou
Medical University from March 2010 to March 2014 were enrolled. qRT-PCR and
immunohistochemistry were applied to examine expression of MTA1 mRNA and protein.
Samples were divided into 6 groups: blank, NC, miR-183 mimics, miR-183
inhibitors, MTA1-siRNA and miR-183 inhibitors +MTA1-siRNA groups. CCK8 method was
employed for determining cell proliferation rate, flow cytometry for cell
apoptosis rate, scratch test for cell migration and Transwell assay for cell
invasion. qRT-PCR and Western blotting were used to determine expression of MTA1,
E-cadherin and Vimentin mRNA and protein. RESULTS: Positive expression rate of
MTA1 was upregulated in PC tissues, and expression of miR-183 and MTA1 was
associated with differentiation, migration, tumor size, TNM. The miR-183 mimics
and MTA1-siRNA groups showed a decrease in proliferation, migration and invasion,
whereas increased apoptosis, in comparison with blank and NC groups, as
expression of MTA1 and Vimentin mRNA and protein were reduced, expression of E
cadherin mRNA and protein was elevated. Compared to blank and NC groups, the miR
183 inhibitors group exhibited enhanced proliferation, migration and invasion and
inhibited apoptosis; increased expressions of MTA1 and Vimentin mRNA and protein
and decreased expressions of E-cadherin mRNA and protein. CONCLUSION: Our study
supported that miR-183 could repress EMT and invasion of human PC cells through
inhibition of MTA1 expression.
PMID- 28506768
TI - Low expression of long non-coding RNA GAS5 is associated with poor prognosis of
patients with thyroid cancer.
AB - The study aims to investigate the role of long non-coding RNA (lncRNA) GAS5 in
the diagnosis and prognosis of patients suffering from thyroid cancer (TC). A
total of 212 patients with TC and 61 patients with benign thyroid tumor were
enrolled in the study. Quantitative real-time polymerase chain reaction (qRT-PCR)
was applied to detect the lncRNA GAS5 expression in TC and benign tumor tissues.
All TC patients were categorized into high-risk and low-risk groups according to
the MACIS, AGES and AMES prognostic scoring system. A 5-year follow-up was
conducted in order to determine the disease free survival (DFS) rates and overall
survival (OS) rates. The associations between lncRNA GAS5 expression and
prognosis of TC patients were analyzed by The Kaplan-Meier survival curves and
the Cox regression models. There was a decrease in the lncRNA GAS5 expression in
TC tissues in comparison to benign tumor tissues. Expression of lncRNA GAS5
showed significant association with tumor node metastasis (TNM) staging, lymph
node metastasis and the multiple cancer foci of TC. AMES high-risk patients
showed a decreased expression of lncRNA GAS5 expression than the AMES low-risk
patients. The AGES and MACIS high-risk patients showed lower lncRNA GAS5
expression than low-risk patients. The survival rate of TC patients with high
lncRNA GAS5 expression was higher than that of TC patients with low lncRNA GAS5
expression during the DFS and OS periods. Cox regression analysis indicated that
lncRNA GAS5 expression, TNM staging, lymph node metastasis and multiple cancer
foci were independent risk factors for poor prognosis in TC patients. LncRNA GAS5
may be closely related to the diagnosis and prognosis of TC.
PMID- 28506767
TI - Mig-6 is down-regulated in HCC and inhibits the proliferation of HCC cells via
the P-ERK/Cyclin D1 pathway.
AB - The ablation of Mig-6 has been shown to induce tumor formation in various
tissues. However, the relationships between Mig-6 expression, clinical
pathological factors, and prognosis have not been clarified in hepatocellular
carcinoma (HCC), and the mechanism by which Mig-6 regulates the proliferation of
HCC cells has not been reported. In this study, we investigated the clinical
significance of the loss of Mig-6 expression in HCC and the mechanism underlying
the inhibition of cell proliferation by Mig-6. The down-regulation of Mig-6
correlated significantly with large tumors, a more advanced BCLC stage, and a
more advanced TNM stage, and low Mig-6 expression predicted significantly reduced
survival. Low Mig-6 expression and high Cyclin D1 expression were independent
predictors for survival. The overexpression of Mig-6 led to significant G1 arrest
and growth inhibition in HCC cells, possibly through the inhibition P-ERK and
Cyclin D1. These results indicate that Mig-6 expression is low in HCC, which
predicts a poor prognosis. Mig-6 may regulate cell proliferation and the cell
cycle through the P-ERK/Cyclin D1 pathway.
PMID- 28506769
TI - Molecular biomarkers for an early diagnosis, effective treatment and prognosis of
colorectal cancer: Current updates.
AB - Colorectal cancer (CRC) is the third most prevalent cancer in the world.
Globally, it has been estimated that about 1.4 million new cases of colorectal
cancer are diagnosed every year. CRC is a multifactorial disease that arises due
to genetics as well as epigenetic alterations in a number of oncogenes, tumor
suppressor genes, mismatch repair genes, as well as cell cycle regulating genes
in colon mucosal cells. These molecular alterations have been considered as
potential CRC biomarkers because they can provide the physicians with diagnostic,
prognostic and treatment response information. The goal is to identify relevant,
cheap and applicable biomarkers that contribute to patient management decisions,
resulting in direct benefits to patients. In this review, we will outline the
most currently available and developing tumor tools, and blood molecular
biomarkers. Also, we will illustrate their diagnostic, therapeutic and prognostic
applications.
PMID- 28506770
TI - Prognostic role of telomere length in malignancies: A meta-analysis and meta
regression.
AB - Telomere length (TL) has been associated with several health conditions including
cancer. To quantify the effect of TL on outcomes in malignancies and explore the
role of type of TL measurement we conducted a librarian-led systematic search of
electronic databases identified publications exploring the prognostic role of TL
on cancer outcomes. Overall survival (OS) was the primary outcome measure while
other time-to-event endpoints were secondary outcomes. Data from studies
reporting a hazard ratio (HR) with 95% confidence interval (CI) and/or p-value
were pooled in a meta-analysis. HRs were weighted by generic inverse variance and
computed by random effects modeling. All statistical tests were two-sided. Sixty
one studies comprising a total of 14,720 patients were included of which 41 (67%)
reported OS outcomes. Overall, the pooled HR for OS was 0.88 (95%CI=0.69-1.11,
p=0.28). Long (versus short) telomeres were associated with improved outcomes in
chronic lymphatic leukemia (CLL) and urothelial cancer (HR=0.45, 95%CI=0.29-0.71
and HR=0.68, 95%CI=0.46-1.00, respectively), conversely worse OS was seen with
hepatocellular carcinoma (HR=1.90, 95%CI=1.51-2.38). Pooled HRs (95% CI) for
progression-free survival, relapse/disease-free survival, cancer-specific
survival, and treatment-free survival were 0.56 (0.41-0.76), 0.76 (0.53-1.10),
0.72 (0.48-1.10), and 0.48 (0.39-0.60), respectively. There was substantial
heterogeneity of tissues and methods used for TL measurement and no clear
association between TL and outcome was identified in subgroups. In conclusion,
there is inconsistent effect of TL on cancer outcomes possibly due to variable
methods of measurement. Standardization of measurement and reporting of TL is
warranted before the prognostic value of TL can be accurately assessed.
PMID- 28506772
TI - Treatment of Epithelioid angiosarcoma with Topical ALA-PDT in the course of
surgery.
AB - BACKGROUND: Epithelioid angiosarcoma is a high grade malignancy sarcoma of soft
tissue, which is hard to diagnose and completely excise without causing
functional and cosmetic problems. Moreover, the high rate of recurrence is hard
to salvage. Photodynamic therapy is a novel treatment protocol which can
selectively destroy tumor cell with good functional and cosmetic outcomes.
METHODS: This is a case about a 81 years old patient with Epithelioid
angiosarcoma in the right medial angle of eye, which received surgery and ALA
photodynamic therapy. RESULTS: There is no recurrence in one year after treatment
of surgery and photodynamic therapy in the course of surgery. CONCLUSIONS:
Excision combined with photodynamic therapy during operation is a promising
strategy towards tumors which are hard to resect thoroughly and have a high risk
of recurrence.
PMID- 28506771
TI - 15d-PGJ2 as an endoplasmic reticulum stress manipulator in multiple myeloma in
vitro and in vivo.
AB - Multiple myeloma (MM) is characterised by intense protein folding and,
consequently endoplasmic reticulum (ER) stress. The prostaglandin 15d-PGJ2 is
able to raise oxidative stress levels within the cell and potentially trigger
cell death. The aim of this study was to evaluate the antineoplastic effect of
15d-PGJ2 on MM in vitro and in vivo via ER and oxidative stress pathways. MM.1R
and MM.1S cell lines were treated with 15d-PGJ2 at 1-10MUM and evaluated with
regard to proliferation, mRNA expression of PRDX1, PRDX4, GRP78, GRP94, CHOP, BCL
2 and BAX. Stress data was validated via oxidized glutathione assays. MM.1R cells
were inoculated into NOD/SCID mice, which were subsequently treated daily with
15d-PGJ2 at 4mg/kg or vehicle (control), with tumour volume being monitored for
14days. 15d-PGJ2 reduced cell proliferation, induced cell death and apoptosis at
5MUM and 10MUM and Stress-related genes were upregulated at the same doses.
Oxidized glutathione levels were also increased. 15d-PGJ2 at 4mg/kg in vivo
halted tumour growth. In conclusion, 15d-PGJ2 induced myeloma cell death via ER
stress in vitro. 15d-PGJ2 in vivo also inhibited tumour growth.
PMID- 28506774
TI - Immunomodulatory and protective effects of adipose tissue-derived mesenchymal
stem cells in an allograft islet composite transplantation for experimental
autoimmune type 1 diabetes.
AB - BACKGROUND: Allogeneic islet transplantation could be an ideal alternative
therapy for Type 1 Diabetes Mellitus (T1DM). Adipose Tissue-derived Mesenchymal
Stem Cells (AT-MSCs) characterized by immunomodulatory and protective effects may
have the potential to improve the outcome of this highly immunogenic transplant.
METHODS: Syngenic AT-MSCs along with allograft islets embedded in hydrogelic
composite and transplanted intraperitoneally in Streptozotocin (STZ) induced
diabetic C57BL/6 mice. RESULTS: In vitro experiments of co-imbedded islets and AT
MSCs in a hydrogel revealed AT-MSCs are able to significantly increase insulin
secretion. During a 32 days of post-transplant period, blood glucose monitoring
showed a decrease from over 400mg/dl to less than 150mg/dl and at the end of 32
days, mice have been dissected and assessed. Graft histopathology demonstrated
that hydrogel makes an artificial immune isolation site and AT-MSCs contribute
greatly to the reduction of the immune cells infiltration. Analyses of
mononuclear cells isolated from Mesenteric Lymph Nodes (MLNs) and spleen showed
that AT-MSCs co-transplanted with allograft decreased pro-inflammatory cytokines
and increased regulatory cytokines (for both MLNs and spleen) and regulatory T
cells (Treg) population (only for MLNs). In addition, real time-PCR assays
revealed that transcript levels of IDO, iNOS, and PDX1, significantly increased
in allograft islets in the presence of AT-MSCs. CONCLUSIONS: according to
results, this investigation indicates that AT-MSCs can be regarded as promising
complementary candidates for engineered-cell therapy using hydrogel composites in
islet transplantation.
PMID- 28506773
TI - Antimicrobial photodynamic therapy with photosensitizer in ethanol improves
oxidative status and gingival collagen in a short-term in periodontitis.
AB - BACKGROUND: This study evaluated the antimicrobial photodynamic therapy (aPDT)
effects using the methylene blue (MB) in ethanol 20% on systemic oxidative status
and collagen content from gingiva of rats with periodontitis. METHODS: Rats were
divided into five experimental groups: NC (negative control; no periodontitis);
PC (positive control; periodontitis without any treatment); SRP (periodontitis
and scaling and root planing), aPDT I (periodontitis and SRP+aPDT+MB solubilized
in water), and aPDT II (periodontitis and SRP+aPDT+MB solubilized in ethanol
20%). After 7days of removal of the ligature, the periodontal treatments were
performed. At 7/15/30days, gingival tissue was removed for morphometric analysis.
The erythrocytes were used to evaluate systemic oxidative status. RESULTS: PC
group showed higher lipoperoxidation levels at 7/15/30days. aPDT indicated a
protective influence in erythrocytes at 15days observed by the elevation in
levels of systemic antioxidant defense. aPDT II group was the only one that
restored the total collagen area in 15days, and recovered the type I collagen
area at the same time point. CONCLUSIONS: aPDT as an adjunct to the SRP can
induce the systemic protective response against oxidative stress periodontitis
induced and recover the gingival collagen, thus promoting the healing
periodontal, particularly when the MB is dissolved in ethanol 20%.
PMID- 28506775
TI - Supervised or Unsupervised Rehabilitation After Total Hip Replacement Provides
Similar Improvements for Patients: A Randomized Controlled Trial.
AB - OBJECTIVE: To determine whether patients do better with unsupervised (home-based)
physiotherapy or in an outpatient setting. SETTING: Acute care public hospital in
the region, supporting a population of ~540,000. DESIGN: Single-blind randomized
controlled trial. PARTICIPANTS: Adult patients (N=98) after unilateral elective
total hip replacement (THR) were randomly assigned to a supervised (center-based)
exercise (n=56) or a unsupervised (home-based) exercise (n=42) program and
followed for 6 months postsurgery. INTERVENTIONS: The supervised group attended a
4-week outpatient rehabilitation program supervised by a physiotherapist. The
unsupervised group was given written and pictorial instructions to perform
rehabilitation independently at home. MAIN OUTCOME MEASURES: Western Ontario and
McMaster Universities Osteoarthritis Index; Short-Form 36-item Health
Questionnaire (SF-36) mental and physical component summary measures; University
of California, Los Angeles activity scale; and timed Up and Go test. RESULTS:
There were no differences between the groups for any measure. The overall
differences between the adjusted means were as follows: Western Ontario and
McMaster Universities Osteoarthritis Index, 0.50 (95% confidence interval [CI],
6.8 to 5.7); SF-36 physical component summary, 0.8 (95% CI, -6.5 to 8.1); SF-36
mental component summary, 1.7 (95% CI, -4.1 to 7.4); University of California,
Los Angeles activity scale, 0.3 (95% CI, 5.2 to 6.1); and timed Up and Go test, 0
seconds (95% CI, -1.4 to 1.3s). CONCLUSIONS: The results demonstrated that
outcomes in response to rehabilitation after THR are clinically and statistically
similar whether the program was supervised or not. The results suggest that early
rehabilitation programs can be effectively delivered unsupervised in the home to
low-risk patients discharged home after THR. However, the relative effect of late
stage rehabilitation was not tested.
PMID- 28506777
TI - Beyond Negative Pain-Related Psychological Factors: Resilience Is Related to
Lower Pain Affect in Healthy Adults.
AB - : Resilience, a characteristic that enhances adaptation in response to stressful
events, is a positive psychological factor that can predict and modulate health
outcomes. However, resilience is rarely considered in pain research. Conversely,
negative psychological factors (eg, anxiety, depression) are known to be related
to the affective dimension of pain. It is critical to understand all potential
psychological drivers of pain affect, a prominent component of chronic pain. We
tested the hypothesis that higher resilience is associated with lower pain
affect, above and beyond the predictive value of negative psychological factors.
Healthy adults underwent psychophysical testing to acquire ratings of heat pain
intensity and unpleasantness and completed the Resilience Scale, the State-Trait
Anxiety Inventory (trait form), Beck Depression Inventory, Pain Catastrophizing
Scale, and the Pain Vigilance and Attention Questionnaire. Multiple regression
modeling (n = 68) showed resilience to be a negatively associated with pain
affect (unpleasantness). Furthermore, in individuals with higher anxiety scores,
resilience was protective against higher pain affect. This highlights the
importance of resilience, a positive psychological factor, in the affective
dimension of pain. This study is the first to assess a positive psychological
factor and experimental pain affect, and has the potential to improve prediction
of and treatment strategies for clinical pain. PERSPECTIVE: We report that
resilience, a positive psychological factor, interacts with anxiety and is
associated with heat pain affect (unpleasantness) in healthy individuals.
Resilience may provide predictive value of chronic pain affect and treatment
outcomes, and could be a target for behavioral therapy.
PMID- 28506778
TI - Genetic Factors Explain the Association Between Pain Catastrophizing and Chronic
Widespread Pain.
AB - : This study aimed to clarify whether there are shared genetic and/or
environmental factors explaining the strong link between pain catastrophizing
(PC) and chronic widespread pain (CWP). Data were available for N = 1,109 female
twins from TwinsUK. Information on self-reported CWP and PC was subject to
variance component twin analysis. Heritabilities were 40% for PC and 77% for CWP.
The genetic correlation between PC and CWP was .40%, whereas no evidence of an
environmental correlation could be detected (.0). According to the best-fitting
additive genetic, non-shared environmental (AE) Cholesky model, an additive
genetic factor loading on PC as well as CWP, as well as an additive genetic
factor loading on CWP alone was found. In terms of environmental influences, 2
individual environmental factors could be identified, loading separately on PC
and CWP. Overall, the results add to the knowledge on the nature of CWP and the
basis of its close relationship with PC by suggesting a shared genetic
etiological structure. The findings highlight a potential avenue for future
research and may provide useful insight for the clinical management of pain and
pain coping. PERSPECTIVE: Results suggest a shared genetic etiological structure
between CWP and PC with no shared influence of environmental factors. Clinicians
should be aware of this biological link within the context of clinical management
of pain and pain coping.
PMID- 28506776
TI - Mindfulness Is Associated With Treatment Response From Nonpharmacologic Exercise
Interventions in Knee Osteoarthritis.
AB - OBJECTIVE: To examine the association between baseline mindfulness and response
from exercise interventions in knee osteoarthritis (OA). DESIGN: Cohort study;
responder analysis of a clinical trial subset. SETTING: Urban tertiary care
academic hospital. PARTICIPANTS: Participants with symptomatic, radiographic knee
OA (N=86; mean age, 60y; 74% female; 48% white). INTERVENTIONS: Twelve weeks
(twice per week) of Tai Chi or physical therapy exercise. MAIN OUTCOME MEASURES:
Treatment response was defined using Osteoarthritis Research Society
International criteria indicating meaningful improvements in the Western Ontario
and McMaster Universities Osteoarthritis Index (WOMAC) pain, WOMAC function, or
Patient Global Assessment scores. At baseline, participants completed the Five
Facet Mindfulness Questionnaire (mean total score, 142+/-17) and were grouped
into 3 categories of total mindfulness: higher, medium, or lower. Relative risk
(RR) ratios were used to compare treatment response across groups. RESULTS:
Participants with higher total mindfulness were 38% (95% confidence interval
[CI], 1.05-1.83) more likely to meet responder criteria than those with lower
mindfulness. We found no significant difference between medium and lower
mindfulness groups (RR=1.0; 95% CI, 0.69-1.44). Among the 5 mindfulness facets,
medium acting-with-awareness was 46% (95% CI, 1.09-1.96) more likely to respond
than lower acting-with-awareness, and higher acting-with-awareness was 34% more
likely to respond, but this did not reach significance (95% CI, 0.97-1.86).
CONCLUSIONS: In this study, higher mindfulness, primarily driven by its acting
with-awareness facet, was significantly associated with a greater likelihood of
response to nonpharmacologic exercise interventions in knee OA. This suggests
that mindfulness-cultivating interventions may increase the likelihood of
response from exercise.
PMID- 28506779
TI - This Gut Ain't Big Enough for Both of Us. Or Is It? Helminth-Microbiota
Interactions in Veterinary Species.
AB - Gastrointestinal helminth parasites share their habitat with a myriad of other
organisms, that is, the commensal microbiota. Increasing evidence, particularly
in humans and rodent models of helminth infection, points towards a multitude of
interactions occurring between parasites and the gut microbiota, with a profound
impact on both host immunity and metabolic potential. Despite this information,
the exploration of the effects that parasite infections exert on populations of
commensal gut microbes of veterinary species is a field of research in its
infancy. In this article, we summarise studies that have contributed to current
knowledge of helminth-microbiota interactions in species of veterinary interest,
and identify possible avenues for future research in this area, which could
include the exploitation of such relationships to improve parasite control and
delay or prevent the development of anthelmintic resistance.
PMID- 28506780
TI - A novel approach for regional anaesthesia of the auricular region in horses: an
anatomic and imaging study.
AB - OBJECTIVE: To investigate the anatomy of the ear innervation in horses and
develop a new approach for the block of the internal and external pinna and
acoustic meatus. STUDY DESIGN: Prospective, descriptive, cadaveric study.
ANIMALS: A total of 25 heads and necks from horse cadavers. METHODS: Phase I:
anatomical dissection and dye deposition on 19 heads. With the head positioned in
lateral recumbency, 10 mL methylene blue (1:1 sterile water) for the internal
auricular and 2 mL for the great auricular nerve block were injected in 21 ears
(seven left, 10 right and two bilaterally). The anatomy of all the ears
(bilaterally) and the accuracy of dye deposition (successful nerve staining
defined as > 2 cm) was assessed following dissection. Occurrence of intraparotid,
intravascular, or intraneural injection was recorded. Phase II: the same
technique and volumes were applied, bilaterally, using a lidocaine 2%:iohexol
solution mixture (3:1) in six different cadavers. Computed tomography was
performed and the needle position and spread of the mixture evaluated and
recorded. RESULTS: Phase I: Inter- and intraindividual differences were found in
the anatomy of the great auricular nerve, but not in the internal and lateral
auricular nerve branches and the caudal auricular nerve. No auriculotemporal
nerve was found. Nerve staining was successful in 95% of the cases for the great
auricular nerve, 85% of the cases for the internal auricular nerve, and 100% of
the cases for the lateral auricular branch and caudal auricular nerve. Failure
was observed in horses with abundant periauricular fat. No intravascular,
intraparotid or intraneural injections occurred. Phase II: A 100% success rate
was recorded from computed tomography images. CONCLUSIONS AND CLINICAL RELEVANCE:
The described approach seems suitable for blockade of the sensory innervation of
the equine ear.
PMID- 28506781
TI - Implementation of quality management for clinical bacteriology in low-resource
settings.
AB - BACKGROUND: The declining trend of malaria and the recent prioritization of
containment of antimicrobial resistance have created a momentum to implement
clinical bacteriology in low-resource settings. Successful implementation relies
on guidance by a quality management system (QMS). Over the past decade
international initiatives were launched towards implementation of QMS in
HIV/AIDS, tuberculosis and malaria. AIMS: To describe the progress towards
accreditation of medical laboratories and to identify the challenges and best
practices for implementation of QMS in clinical bacteriology in low-resource
settings. SOURCES: Published literature, online reports and websites related to
the implementation of laboratory QMS, accreditation of medical laboratories and
initiatives for containment of antimicrobial resistance. CONTENT: Apart from the
limitations of infrastructure, equipment, consumables and staff, QMS are
challenged with the complexity of clinical bacteriology and the healthcare
context in low-resource settings (small-scale laboratories, attitudes and
perception of staff, absence of laboratory information systems). Likewise, most
international initiatives addressing laboratory health strengthening have focused
on public health and outbreak management rather than on hospital based patient
care. Best practices to implement quality-assured clinical bacteriology in low
resource settings include alignment with national regulations and public health
reference laboratories, participating in external quality assurance programmes,
support from the hospital's management, starting with attainable projects,
conducting error review and daily bench-side supervision, looking for locally
adapted solutions, stimulating ownership and extending existing training
programmes to clinical bacteriology. IMPLICATIONS: The implementation of QMS in
clinical bacteriology in hospital settings will ultimately boost a culture of
quality to all sectors of healthcare in low-resource settings.
PMID- 28506782
TI - The misleading effect of serum galactomannan testing in high-risk haematology
patients receiving prophylaxis with micafungin.
AB - OBJECTIVES: To investigate the performance of the routine serum galactomannan
(sGM) assay in the diagnosis of invasive aspergillosis (IA) in high-risk
haematology patients receiving prophylaxis with micafungin. METHODS:
Retrospective study including all haematological patients who received
prophylaxis with micafungin during high-risk IA episodes (neutropenic patients
after chemotherapy for acute myeloid leukaemia/myelodysplastic syndrome;
allogeneic haematopoietic stem-cell transplantation during early neutropenic
phase or graft-versus-host disease requiring high prednisone doses) and for whom
at least one sGM result was available. Episodes were classified as follows: true
positive (positive GM in the context of IA), false-positive (positive GM result
in patients who had no evidence of IA), true-negative (negative GM test results
and no IA), or false-negative (negative GM test in the context of IA). Non
evaluable patients were excluded. RESULTS: Among 146 evaluable episodes, four
were true-positive in the context of probable breakthrough IA (incidence of
breakthrough IA, 2.7%); 111/146 high-risk episodes (76%) were considered true
negative and 31/146 (21.2%) were considered false-positive. No false-negative
episodes were detected. All but one of the false-positive episodes were detected
in surveillance GM tests, leading to high-resolution CT scans in eight cases
(8/31; 25.8%), all of which were negative. The positive predictive and negative
predictive values of sGM for surveillance and diagnostic approaches were 3.2%
(1/31) and 100% (110/110) and 75% (3/4) and 100% (1/1), respectively.
CONCLUSIONS: Surveillance of asymptomatic patients receiving prophylaxis with
micafungin using sGM is unnecessary, because the results are either negative or
false-positive. However, sGM remains useful in the diagnosis of breakthrough IA
in symptomatic patients during prophylaxis.
PMID- 28506783
TI - The professional status of infectious disease physicians in China: a nationwide
cross-sectional survey.
AB - OBJECTIVES: The evolution of infectious diseases (IDs) poses a challenge to many
ID physicians, who must either adapt or transition to another career track. This
national cross-sectional study assessed the current working conditions and
problems faced by ID professionals in China. METHODS: A national questionnaire
survey of ID physicians and their facilities throughout China was performed in
May-June 2016 using stratified random sampling. RESULTS: A total of 156/300
(52.0%) ID departments and 1071/2250 (47.6%) physicians from 21 provinces
participated in the survey. Overall, 151 (96.2%) of 156 hospitals had ID wards
and 141 (90.4%) provided outpatient consultations. The average number of ID
physicians per department was 10.32 +/- 6.57. The ratio of patient beds to
doctors was 5: 1, and the ratio of patient beds to nurses was 5: 1.85. Training
in IDs was available in 126 (80.8%), and ID research was performed in 108
(69.2%), of the 156 departments. The main service provided by ID physicians was
the management of legally notifiable communicable diseases. The annual income of
942 (88.0%) of the 1071 physicians was below $15 000. Of these physicians, 870
(81.2%) felt high or very high pressure in their work, whereas only 514 (48.0%)
were satisfied or very satisfied with their jobs. CONCLUSIONS: The limited
medical service provided by ID physicians is poorly aligned with current
healthcare demands. Moreover, the heavy workloads, high stress, poor compensation
and limited career prospects for ID physicians in China impede the continued
development of specialists and places them in a career dilemma. ID physicians
should work to develop and diversify the field and to enhance their capacities by
learning new technologies and collaborating with other medical disciplines.
PMID- 28506784
TI - Healthcare personnel intestinal colonization with multidrug-resistant organisms.
AB - OBJECTIVES: This study aims to assess the association between patient contact and
intestinal carriage of multidrug-resistant organisms (MDRO) by sampling
healthcare personnel (HCP) and staff without patient contact. METHODS: For this
observational study, we recruited 400 HCP who worked in our 200-bed research
hospital and 400 individuals without patient contact between November 2013 and
February 2015. Participants submitted two self-collected perirectal swabs and a
questionnaire. Swabs were processed for multidrug-resistant Gram-negative
bacteria and vancomycin-resistant enterococci (VRE). Questionnaires explored
occupational and personal risk factors for MDRO carriage. RESULTS: Among 800
participants, 94.4% (755/800) submitted at least one swab, and 91.4% (731/800)
also submitted questionnaires. Extended spectrum beta-lactamase-producing
organisms were recovered from 3.4% (26/755) of participants, and only one
carbapenemase-producing organism was recovered. No VRE were detected. The
potential exposure of 68.9% (250/363) of HCP who reported caring for MDRO
colonized patients did not result in a rate of MDRO carriage among HCP (4.0%;
15/379) significantly higher than that of staff without patient contact (3.2%;
12/376; p 0.55). CONCLUSIONS: This is the largest US study of HCP intestinal MDRO
carriage. The low colonization rate is probably reflective of local community
background rates, suggesting that HCP intestinal colonization plays a minor role
in nosocomial spread of MDROs in a non-outbreak setting. TRIAL REGISTRATION:
clinicaltrials.gov Identifier: NCT01952158.
PMID- 28506785
TI - What can we learn from our peer reviewers.
PMID- 28506786
TI - Diagnostic test accuracy of antigenaemia assay for PCR-proven cytomegalovirus
infection-systematic review and meta-analysis.
AB - OBJECTIVES: We aimed to assess diagnostic test accuracy of antigenaemia assay for
PCR-proven cytomegalovirus (CMV) infection. METHODS: We systematically searched
studies that provide data both on sensitivity and specificity of the CMV
antigenaemia assay using the PCR as the reference standard. Adults, children,
infants, individuals who were immunocompromised for any reason, symptomatic
patients and asymptomatic individuals were all included. A hierarchical summary
receiver operating characteristics model was used for diagnostic meta-analysis.
Study quality was assessed by Revised Tool for the Quality Assessment of
Diagnostic Accuracy Studies. Protocol registration identification is
CRD42016035892. RESULTS: We identified 75 eligible articles including 9058 CMV
PCR-positive individuals and 22 232 PCR-negative individuals. The diagnostic odds
ratio for positive antigenaemia was 30 (95% CI 24-38, I2 = 28%) and the area
under the hierarchical summary receiver operating characteristic curve was 0.86
(95% CI 0.83-0.88). The summary estimates of sensitivity and specificity were
0.65 (95% CI 0.59-0.70) and 0.94 (95% CI 0.93-0.95), respectively. The positive
likelihood ratio of 10.9 (95% CI 8.5-14.0) suggested that a positive result from
the antigenaemia assay greatly increased the probability of PCR-proven CMV
infection, but a negative likelihood ratio of 0.38 (95% CI 0.32-0.44) indicated
that a negative result led to a small decrease in the probability of PCR-proven
CMV infection. Sensitivity and subgroup analyses replicated these results.
CONCLUSIONS: The antigenaemia assay overlooked 35% of PCR-proven CMV infections;
hence, a negative result of an antigenaemia assay could not rule out a CMV
infection.
PMID- 28506788
TI - In Reply to 'Assessing the Effect of Spironolactone on Acute Kidney Injury After
Cardiac Surgery'.
PMID- 28506789
TI - Assessing the Effect of Spironolactone on Acute Kidney Injury After Cardiac
Surgery.
PMID- 28506787
TI - Empyema thoracis caused by an optrA-positive and linezolid-intermediate
Enterococcus faecalis strain.
PMID- 28506790
TI - Single particle labeling of RNA virus in live cells.
AB - Real-time and visual tracking of viral infection is crucial for elucidating the
infectious and pathogenesis mechanisms. To track the virus successfully, an
efficient labeling method is necessary. In this review, we first discuss the
practical labeling techniques for virus tracking in live cells. We then describe
the current knowledge of interactions between RNA viruses (especially influenza
viruses, immunodeficiency viruses, and Flaviviruses) and host cellular
structures, obtained using single particle labeling techniques combined with real
time fluorescence microscopy. Single particle labeling provides an easy system
for understanding the RNA virus life cycle.
PMID- 28506791
TI - Enterovirus 71-induced has-miR-21 contributes to evasion of host immune system by
targeting MyD88 and IRAK1.
AB - Enterovirus71(EV71), the etiological agent of hand-foot-and-mouth disease, has
increasingly become a public health challenge around the world. Type I
interferons (IFNs) are an important family of cytokines that regulate innate and
adaptive immune responses to pathogens.These pathways are tightly regulated by
the host to prevent an inappropriate cellular response, but viruses can modulate
these pathways to proliferate and spread. In this study, we demonstrated that
EV71 evades the immune surveillance system to proliferate by activating microRNA
21. We demonstrated that EV71 infection upregulates miR-21, which in turn
suppresses EV71-triggered type I IFN production, thus promoting EV71 replication.
Furthermore, we demonstrated that miR-21 targets the myeloid differentiation
factor 88(MyD88) and interleukin-1 receptor-associated kinase 1(IRAK1), which are
involved in EV71-induced type I IFN production.
PMID- 28506792
TI - Discovery of a novel canine respiratory coronavirus support genetic recombination
among betacoronavirus1.
AB - Although canine respiratory coronavirus (CRCoV) is an important respiratory
pathogen that is prevalent in many countries, only one complete genome sequence
of CRCoV (South Korea strain K37) has been obtained to date. Genome-wide analyses
and recombination have rarely been conducted, as small numbers of samples and
limited genomic characterization have previously prevented further analyses.
Herein, we report a unique CRCoV strain, denoted strain BJ232, derived from a
CRCoV-positive dog with a mild respiratory infection. Phylogenetic analysis based
on complete genome of all available coronaviruses consistently show that CRCoV
BJ232 is most closely related to human coronavirus OC43 (HCoV-OC43) and BCoV,
forming a separate clade that split off early from other Betacoronavirus 1. Based
on the phylogenetic and SimPlot analysis we propose that CRCoV-K37 was derived
from genetic recombination between CRCoV-BJ232 and BCoV. In detail, spike (S)
gene of CRCoV-K37 clustered with CRCoV-BJ232. However orf1ab, membrane (M) and
nucleocapsid (N) genes were more related to Bovine coronavirus (BCoV) than CRCoV
B232. Molecular epidemic analysis confirmed the prevalence of CRCoV-BJ232 lineage
around the world for a long time. Recombinant events among Betacoronavirus 1 may
have implications for CRCoV transmissibility. All these findings provide further
information regarding the origin of CRCoV.
PMID- 28506793
TI - Frequency and risk-factors analysis of Escherichia coli O157:H7 in Bali-cattle.
AB - Cattle are known as the main reservoir of zoonotic agents verocytotoxin-producing
Escherichia coli. These bacteria are usually isolated from calves with diarrhea
and/or mucus and blood. Tolerance of these agents to the environmental conditions
will strengthen of their transmission among livestock. A total of 238 cattle
fecal samples from four sub-districts in Badung, Bali were used in this study.
Epidemiological data observed include cattle age, sex, cattle rearing system, the
source of drinking water, weather, altitude, and type of cage floor, the
cleanliness of cage floor, the slope of cage floor, and the level of cattle
cleanliness. The study was initiated by culturing of samples onto eosin methylene
blue agar, then Gram stained, and tested for indole, methyl-red, voges proskauer,
and citrate, Potential E.coli isolates were then cultured onto sorbitol MacConkey
agar, and further tested using O157 latex agglutination test and H7 antisera.
Molecular identification was performed by analysis of the 16S rRNA gene, and
epidemiological data was analyzed using STATA 12.0 software. The results showed,
the prevalence of E. coli O157:H7 in cattle at Badung regency was 6.30% (15/238)
covering four sub districts i.e. Petang, Abiansemal, Mengwi, and Kuta which their
prevalence was 8.62%(5/58), 10%(6/60), 3.33%(2/60), and 3.33(2/60)%,
respectively. The analysis of 16S rRNA gene confirmed of isolates as an E. coli
O157:H7 strain with 99% similarities. Furthermore, the risk factors analysis
showed that the slope of the cage floor has a highly significant effect (P<0.05)
to the distribution of infection. Consequently, implementing this factor must be
concerned in order to decrease of infection.
PMID- 28506794
TI - Life-shortening Wolbachia infection reduces population growth of Aedes aegypti.
AB - Wolbachia bacteria are being introduced into natural populations of vector
mosquitoes, with the goal of reducing the transmission of human diseases such as
Zika and dengue fever. The successful establishment of Wolbachia infection is
largely dependent on the effects of Wolbachia infection to host fitness, but the
effects of Wolbachia infection on the individual life-history traits of immature
mosquitoes can vary. Here, the effects of life-shortening Wolbachia (wMelPop) on
population growth of infected individuals were evaluated by measuring larval
survival, developmental time and adult size of Aedes aegypti in intra- (infected
or uninfected only) and inter-group (mixed with infected and uninfected) larval
competition assays. At low larval density conditions, the population growth of
wMelPop infected and uninfected individuals was similar. At high larval
densities, wMelPop infected individuals had a significantly reduced population
growth rate relative to uninfected individuals, regardless of competition type.
We discuss the results in relation to the invasion of the wMelPop Wolbachia
infection into naturally uninfected populations.
PMID- 28506795
TI - Parallel ELISAs using crude soluble antigen and excretory-secretory antigen for
improved serodiagnosis of amoebic liver abscess.
AB - Crude soluble antigen (CSA) produced from Entamoeba histolytica trophozoite is
conventionally used for serodiagnosis of invasive amoebiasis. However, high
background seropositivities by CSA-assay in endemic areas complicate the
interpretation of positive result in clinical settings. Instead, incorporating a
second assay which indicates active or recent infection into the routine amoebic
serology could possibly complement the limitations of CSA-assay. Hence, the
present study aimed to evaluate the diagnostic efficacies of indirect ELISAs
using CSA and excretory-secretory antigen (ESA) for serodiagnosis of amoebic
liver abscess (ALA). Reference standard for diagnosis of ALA at Hospital
Universiti Sains Malaysia is based on clinical presentation, radiological imaging
and positive indirect haemagglutination assay (titer >=256). Five groups of human
serum samples collected from the hospital included Group I - ALA diagnosed by the
reference standard and pus aspirate analysis using real-time PCR (n=10), Group II
- ALA diagnosed by the reference standard only (n=41), Group III - healthy
control (n=45), Group IV - other diseases control (n=51) and Group V - other
infectious diseases control (n=31). For serodiagnosis of ALA serum samples (Group
I and II), CSA-ELISA showed sensitivities of 100% for both groups, while ESA
ELISA showed sensitivities of 100% and 88%, respectively. For serodiagnosis of
non-ALA serum samples (Group III, IV and V), CSA-ELISA showed specificities of
91%, 75% and 100%, respectively; while ESA-ELISA showed specificities of 96%, 98%
and 100%, respectively. Indirect ELISAs using CSA and ESA have shown distinct
strength for serodiagnosis of ALA, in terms of sensitivity and specificity,
respectively. In conclusion, parallel analysis by both assays improved the
overall efficacies of amoebic serology as compared to either single assay.
PMID- 28506797
TI - [Systematic proposal of fertility preservation by mature oocyte cryopreservation
for recurrent benign ovarian tumors].
AB - OBJECTIVES: To investigate prospectively the pattern of the follicular growth and
to characterize the COH outcome in terms of oocyte number and maturity in
patients with voluminous recurrent benign ovarian tumors with a high surgical
risk of significant reduction of the ovarian follicular content. METHODS: The
inclusion criteria were: age between 18 and 36, presence of at least one benign
ovarian tumor (>= 5cm) with high risk of recurrence. The fertility preservation
cycle was performed at least 3 months after the cyst surgery. The controlled
ovarian stimulation was performed after the ovarian reserve was assessed (AMH
measurement and sonographic antral follicle count). Triggering was performed by
hCG when at least 3 follicles reached 18mm of diameter. Metaphase II oocytes were
cryopreserved by the vitrification technique. RESULTS: Twenty-four women with
dermoid, endometrioma or seromucinous cysts were included from January 2015 to
July 2016. All of them had previous ovarian surgery. Mean AMH levels were
15.3pmol/L. The mean number of total oocytes retrieved was 7+/-5. The mean number
of metaphase II oocytes was 4.4+/-4. The incidence of low ovarian response was
38%. Among the patients, 86% had less than 8 metaphase II oocytes vitrified.
Seven patients asked for a second cycle in order to have more oocytes.
CONCLUSION: We demonstrated the feasibility of the systematic proposal of
fertility preservation by oocyte cryopreservation in this group of young patients
with recurrent ovarian benign tumors. Taking into account history of previous
surgery and high incidence of low ovarian reserve, the ovarian response under
stimulation was frequently poor with, as consequence, low retrieved oocyte number
per cycle. An oocyte accumulation strategy is then proposed to enhance further
pregnancy chances.
PMID- 28506796
TI - From head to toe: Sex and gender differences in the treatment of ischemic
cerebral disease.
AB - Stroke is a major cause of mortality and morbidity, particularly in the older
ages. Women have a longer life expectancy and are more likely to experience
stroke than men. Interestingly, the increased risk of ischemic stroke in women
seems to be independent from age or classical cardiovascular risk factors.
Notwithstanding the fact that stroke outcomes and survival are usually poorer in
women, current evidence suggests that thrombolysis, antiplatelet and
anticoagulant therapies are more beneficial in women than in men. A possible
explanation of this paradox might be that females are often undertreated and they
have fewer chances to be submitted to an effective and timely treatment for
stroke than the male counterpart. The first step in the attempt to solve this
obvious discrimination is surely to emphasize any reasons for differences in the
therapeutic approach in relation to gender and then to denounce the lack of a
sustainable motivation for them. In this article, we aimed to review the existing
literature about gender-related differences on efficacy, administration and side
effects of the most common drugs used for the treatment of ischemic stroke. The
most striking result was the evidence that the therapeutic approach for stroke is
often different according to patients' gender with a clear detrimental prognostic
effect for women. A major effort is necessary to overcome this problem in order
to ensure equal right to treatment without any sexual discrimination.
PMID- 28506799
TI - Diffusion-weighted imaging in quiescent Crohn's disease: correlation with
inflammatory biomarkers and video capsule endoscopy.
AB - AIM: To investigate the role of restricted diffusion in quiescent Crohn's disease
(CD) patients and its association with inflammatory biomarkers and endoscopic
disease. MATERIAL AND METHODS: Fifty-two quiescent CD patients prospectively
underwent magnetic resonance enterography (MRE) and video capsule endoscopy (VCE)
and were tested for the inflammatory biomarkers, faecal calprotectin (FCP) and C
reactive protein (CRP). Restricted diffusion in the distal ileum was
qualitatively (absence/presence) and quantitatively (apparent diffusion
coefficient [ADC]) assessed by two readers. The VCE-based Lewis score was
calculated for the distal ileum. Restricted diffusion sensitivity and specificity
for VCE ulcerations were assessed for patients with elevated (>100 MUg/g) or
normal (<100 MUg/g) FCP. Receiver operating characteristic (ROC) curve was used
to assess the ability of ADC to identify patients with concurrent VCE ulceration
and elevated FCP. RESULTS: The sensitivity and specificity of restricted
diffusion for patients with VCE ulceration were higher in patients with elevated
FCP (reader 1: 71.4%, 80%, reader 2: 76.2%, 100%, respectively) compared to
patients with normal FCP (reader 1: 46.2%, 61.5%; reader 2: 15.4%, 76.9%,
respectively). The ADC had a high diagnostic accuracy for identifying patients
that had concurrent VCE ulceration and elevated FCP (reader 1: AUC=0.819, reader
2: AUC=0.832). CONCLUSION: In quiescent CD patients, the presence of restricted
diffusion is suggestive of an active inflammation, associated with elevated FCP.
Thus, DWI may serve as a clinical tool in the follow-up of these patients,
implying subclinical inflammatory flares.
PMID- 28506798
TI - Evaluation of a semi-automated software program for the identification of
vertebral fractures in children.
AB - AIM: To assess observer reliability and diagnostic accuracy in children, of a
semi-automated six-point technique developed for vertebral fracture (VF)
diagnosis in adults, which records percentage loss of vertebral body height.
MATERIALS AND METHODS: Using a semi-automated software program, five observers
independently assessed T4 to L4 from the lateral spine radiographs of 137
children and adolescents for VF. A previous consensus read by three paediatric
radiologists using a simplified algorithm-based qualitative technique (i.e., no
software involved) served as the reference standard. RESULTS: Of a total of 1,781
vertebrae, 1,187 (67%) were adequately visualised according to three or more
observers. Interobserver agreement in vertebral readability for each vertebral
level for five observers ranged from 0.05 to 0.47 (95% CI: -0.19, 0.76). Intra
observer agreement using the intraclass correlation coefficient (ICC) ranged from
0.25 to 0.61. The overall sensitivity and specificity were 18% (95% CI: 14-22)
and 97% (95% CI: 97-98), respectively. CONCLUSION: In contrast to adults, the six
point technique assessing anterior, middle, and posterior vertebral height ratios
is neither satisfactorily reliable nor sensitive for VF diagnosis in children.
Training of the software on paediatric images is required in order to develop a
paediatric standard that incorporates not only specific vertebral body height
ratios but also the age-related physiological changes in vertebral shape that
occur throughout childhood.
PMID- 28506800
TI - Behaviour of silver nanoparticles in simulated saliva and gastrointestinal
fluids.
AB - Continuously increasing application of silver nanoparticles (AgNPs) requires
information on their safety and performance under biological conditions.
Assessment of AgNPs in biological systems is also related to availability of
robust toxicological methods for evaluation of toxic potential of AgNPs and
information on their physicochemical state. Silver nanoparticles were subjected
to action of simulated saliva, gastric and intestinal fluids, appropriately
supplemented with digestive enzymes pepsin or pancreatin. The behaviour of AgNPs
was determined using dynamic light scattering and transmission electron
microscopy, and their toxicity as well as capability to induce inflammatory
reactions were assessed using reconstructed human tissue models (EpiOral,
EpiGingival, EpiIntestinal). The study revealed that during exposure to the
fluids, AgNPs size and morphology changed and depended on composition and pH of
the respective fluid. If present, the change in terms of growth of AgNPs size
occurred immediately after contact of AgNPs with the respective fluid and
continued with prolonged time of contact. A pilot study on reconstituted human
tissue models revealed low toxicity and inflammatory effects of AgNPs and
confirmed the suitability of 3-D models for toxicological studies including
bioavailability.
PMID- 28506801
TI - Old drug, new wrapping - A possible comeback for chloramphenicol?
AB - The antimicrobial drug chloramphenicol (CAM) exhibits activity against resistant
bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). However,
its use has been limited due to its toxicity. As the threat of antibiotic
resistance continues to grow, a promising approach might be to increase the use
of historical antimicrobial agents that demonstrate clinical efficacy, but are
hampered by toxicity. We therefore aimed to prepare a liposome-in-hydrogel system
for dermal delivery of CAM. Chitosan (CS) was used as the hydrogel vehicle due to
its antimicrobial activity and excellent biocompatibility. All critical
preparation steps were carried out by dual centrifugation (DC). The DC-method
proved to be fast and simple, and organic solvents were avoided in all processing
steps. Liposomes with high drug entrapment (49-56%), low polydispersity and a
size of approximately 120nm were produced. Mixing of liposomes into CS-hydrogel
by DC produced a homogenous liposomes-in-hydrogel system. Bioadhesive properties
were good and comparable to plain CS-hydrogel formulations. Ex vivo permeation
studies using pig skin indicated a sustained release of CAM and limited skin
permeation. The in vitro antimicrobial activity of CAM in the new liposome-in
hydrogel formulation was similar or better as compared to CAM in solution. Thus,
the new formulation was considered highly promising.
PMID- 28506802
TI - Stealth magnetic nanocarriers of siRNA as platform for breast cancer
theranostics.
AB - The endogenous mechanism of RNA interference is more and more used in research to
obtain specific down-regulation of gene expression in diseases such as breast
cancer. Currently, despite the new fields of study open up by RNA interference,
the rapid degradation of siRNA by nucleases and their negative charges prevent
them from crossing cell membranes. To overcome these limitations,
superparamagnetic iron oxide nanoparticles (SPIONs) represent a promising
alternative for nucleic acid delivery. Previously, we reported the magnetic siRNA
nanovectors (MSN) formulation using electrostatic assembly of (1) SPIONs, also
able to act as contrast agents for magnetic resonance imaging (MRI), (2) siRNA
and (3) chitosan aiming at their protection and enhancing their transfection
efficacy. However, these nanoparticles displayed low stability in biological
suspensions and inefficient transfection of active siRNA. This work aimed at
upgrading MSN to Stealth MSN (S-MSN) by adding a polyethylene glycol coating to
ensure colloidal stability and stealth properties. Furthermore, another polymer
(poly-L-arginine) was added for efficient siRNA transfection and the quantitative
composition of the formulation was adapted for biological purposes. Results
showed that S-MSN provide high siRNA complexation and protection against
enzymatic degradation. Green fluorescent protein (GFP) specific down-regulation
on MDA-MB231/GFP cells was comparable to that of commercially available reagents,
without observable cytotoxicity. According to our works, S-MSN appears as an
effective formulation for in vitro siRNA specific delivery.
PMID- 28506803
TI - PEG coated and doxorubicin loaded multimodal Gadolinium oxide nanoparticles for
simultaneous drug delivery and imaging applications.
AB - We report water-in-oil microemulsion mediated synthesis of PEG1 coated Gd2O3 NPs2
loaded with fluorescent anti-cancer drug dox3 for synchronous drug delivery,
optical and MR4 imaging applications. These PEG covered Gd2O3 NPs loaded with dox
(Gd-PEG-dox NPs) were found to possess spherical morphology with 13nm size as
measured from TEM and the hydrodynamic diameter comes out to be 37nm as
determined from DLS. Fluorescence spectra and fluorescence microscopy images
confirmed optical activity of the NPs. The paramagnetic nature of NPs was
affirmed by NMR line broadening effect on the spectrum of surrounding water
protons. Therefore, these particles can be efficiently used as CA5 in MR imaging.
In vitro analysis showed significant cellular uptake of particles by A-549 cells.
A pH dependent drug release pattern was observed for the NPs. Cell viability
assay performed on A-549, PANC-1 and U-87 cancerous cell lines revealed that Gd
PEG-dox NPs are cytotoxic. On the basis of these observations, it can be
concluded that these multi-modal paramagnetic NPs promise potential cancer
therapy along with optical and MR imaging applications.
PMID- 28506804
TI - Chloroquine enhances the antimycobacterial activity of isoniazid and pyrazinamide
by reversing inflammation-induced macrophage efflux.
AB - Mycobacterium tuberculosis (MTB) is notorious for persisting within host
macrophages. Efflux pumps decrease intracellular drug levels, thus fostering
persistence of MTB during therapy. Isoniazid (INH) and pyrazinamide (PZA) are
substrates of the efflux pump breast cancer resistance protein-1 (BCRP-1), which
is inhibited by chloroquine (CQ). In this study, BCRP-1 was found to be expressed
on macrophages of human origin and on foamy giant cells at the site of MTB
infection. In the current in vitro study, interferon-gamma (IFNgamma) increased
the expression of BCRP-1 in macrophages derived from the human monocytic
leukaemia cell line THP-1. Using a BCRP-1-specific fluorescent dye and
radioactively labelled INH, it was demonstrated that efflux from macrophages
increased upon activation with IFNgamma. CQ was able to inhibit active efflux and
augmented the intracellular concentrations both of INH and the dye. In agreement,
CQ and specific inhibition of BCRP-1 increased the antimycobacterial activity of
INH against intracellular MTB. Although PZA behaved differently, CQ had
comparable advantageous effects on the intracellular pharmacokinetics and
activity of PZA. The adjunctive effects of CQ on intracellular killing of MTB
were measurable at concentrations achievable in humans at approved therapeutic
doses. Therefore, CQ, a widely used and worldwide available drug, may potentiate
the efficacy of standard MTB therapy against bacteria in the intracellular
compartment.
PMID- 28506805
TI - HDL abnormalities in familial hypercholesterolemia: Focus on biological
functions.
AB - Although a selective strong elevation in the plasma level of low-density
lipoprotein (LDL) cholesterol is the hallmark of familial hypercholesterolemia
(FH), also other plasma lipoprotein and lipid subspecies are changed in these
patients. Several studies in FH patients have pointed to the qualitative
abnormalities of high-density lipoprotein (HDL) particles, including their
triglyceride and sphingomyelin enrichment, reduced capacity to promote
cholesterol efflux from macrophages, impaired anti-inflammatory and anti-oxidant
activities, and reduced plasma levels of miRs regulating HDL-dependent
cholesterol efflux from macrophage foam cells, typical of atherosclerotic
lesions. Thus, accurate understanding of HDL functionality and its disturbances
in FH may serve a better estimation of the prognosis and also provide additional
clues when searching for novel therapeutic choices in this disease. In spite of
such a potential promise, there has been no prior comprehensive review focusing
on indices of HDL function in FH patients. In the present review, we aim to
fulfill this gap by identifying measures of HDL function that are impaired in FH,
and by providing a concise summary on the impact of different lipid-modifying
therapies on HDL functionality in FH.
PMID- 28506806
TI - Selective associative phonagnosia after right anterior temporal stroke.
AB - We report the case of a 48 year old men who developed a selective impairment in
famous voice recognition after ischemic stroke in right subcortical structures
(lenticular nucleus and head of the caudate) and right anterior temporal lobe. He
underwent fibrinolytic treatment. During the following days he progressively
recovered and was discharged without neurological focal sign. Patent foramen
ovale was found. When he got back to his house he noticed that he was unable to
recognize the voice of his favoured singers and needed to ask who was the singer
to his relatives. Neuropsychological examination revealed a selective impairment
in famous voice recognition in the absence of alteration of voice perception,
face perception and famous face recognition. All other neuropsychological domains
were spared. In particular language, memory and executive functions were intact.
Neuroimaging carried out by means of PET and MRI revealed two small ischemic
lesions in the right subcortical region, involving lenticular and caudate nuclei
and in the right temporal pole. To our knowledge, this is the first case
described in literature of a patient showing a selective associative phonagnosia
after right anterior temporal stroke. The present case helps to clarify the brain
circuits underlying famous voice recognition and adds evidence in favour of a
right hemisphere involvement in processing knowledge of familiar voices. These
findings are discussed in relation to current models of brain organization of
person-specific and general semantic knowledge.
PMID- 28506807
TI - Phoneme processing skills are reflected in children's MMN responses.
AB - Phonological awareness (PA), the core contributor in phoneme processing
abilities, has a link to later reading skills in children. However, the
associations between PA and neural auditory discrimination are not clear. We used
event-related potential (ERP) methodology and neuropsychological testing to
monitor the neurocognitive basis of phonological awareness in typically
developing children. We measured 5-6-year-old children's (N=70) phoneme
processing, word completion and perceptual reasoning skills and compared their
test results to their brain responses to phonemic changes, separately for each
test. We found that children performing better in Phoneme processing test showed
larger mismatch negativity (MMN) responses than children scoring lower in the
same test. In contrast, no correspondence between test scores and brain responses
was found for Auditory closure. Thus, the results suggest that automatic auditory
change detection is linked to phoneme awareness in preschool children.
PMID- 28506808
TI - Should subcutaneous implantable cardioverter-defibrillators be implanted in
patients who are candidates for continuous flow left ventricular assist device?
PMID- 28506809
TI - Women with atrial fibrillation and type 2 diabetes have a higher incidence of
hospitalization and undergo ablation or pacemaker implantation less frequently
than men.
AB - BACKGROUND: We reviewed trends from 2004 to 2013 in the incidence and outcomes
for atrial fibrillation (AF) in Spanish patients with type 2 diabetes mellitus
(T2DM) comparing women and men. METHODS: We used national hospital discharge data
including all T2DM patients discharged from the hospital after AF. Patients with
AF in the primary diagnosis field were selected. Discharges were grouped by sex.
Incidence was calculated overall and stratified by sex. We analyzed diagnostic
and therapeutic procedures, patient comorbidities, CHA2DS2-VASc score, length of
hospital stay, readmission rates and in-hospital mortality (IHM). RESULTS: We
identified a total of 214,457 admissions for AF. Patients with T2DM accounted for
21.1% (19,505 men and 25,954 women). Women with T2DM had a significantly higher
incidence of AF compared to men over the study period (IRR 1.33;95%CI 1.31-1.35).
Women were significantly older (77.24+/-8.69years) than men (72.62+/-10.28years),
had higher prevalences of obesity and hypertension, and higher CHA2DS2-VASc
score. Women less frequently underwent ablation (3.21% vs. 1.54%; p<0.001) and
received an implanted pacemaker (14.3% vs. 8.16%; p<0.001) than men. Crude IHM
was 2.81% for women and 2.48% for men (p=0.030). Sex was not associated with a
higher IHM after multivariable adjustment. CONCLUSIONS: Our study demonstrates an
increase in hospitalization for AF in diabetic women. Women were older, had a
higher comorbidity index and had CHAD2DS2-VASc score than men. Women with AF and
T2DM undergo ablation or pacemaker implantation less frequently than their male
counterparts. After multivariable adjustment sex did not predict mortality during
admissions for AF.
PMID- 28506810
TI - A man with dyspnea, chest pain and leukocytosis.
PMID- 28506811
TI - A young woman with fever and low visual acuity.
PMID- 28506812
TI - A 33year-old woman with calciphylaxis, diabetic kidney disease and abdominal
pain.
PMID- 28506813
TI - The Effects of Natural Clinoptilolite and Nano-Sized Clinoptilolite
Supplementation on Glucose Levels and Oxidative Stress in Rats With Type 1
Diabetes.
AB - OBJECTIVE: Oxidative stress has a major role in development of diabetic
complications. In this study we investigated whether clinoptilolite and nano
sized clinoptilolite could reduce hyperglycemia and oxidative stress in
streptozotocin-induced diabetic rats and attempted to determine which
intervention was more effective. METHODS: Thirty-six rats were randomly allocated
to 2 groups; 1 group was randomly chosen as a diabetic group and injected with
streptozotocin (60 mg/kg body weight in 0.1 mol/L sodium citrate buffer, pH 4.5)
to induce diabetes. Three days after diabetes induction, each group (diabetic
group and nondiabetic group) was randomly divided into 3 subgroups of 6 animals
each ([1] control, [2] 1% clinoptilolite/food, [3] 1% nano-sized
clinoptilolite/food). Supplementation was continued for 28 days. Blood glucose
was measured 3 times, at the beginning of the study and on the 14th and 28th
days. Activity of antioxidant enzymes, including glutathione peroxidase and
superoxide dismutase, and levels of total antioxidant capacity, as well as
malondialdehyde, were evaluated. RESULTS: Blood glucose and malondialdehyde were
significantly elevated, but there were no statistically significant changes in
superoxide dismutase, glutathione peroxidase or total antioxidant capacity in
diabetic rats. In diabetic rats treated with nano-sized clinoptilolite, blood
glucose decreased to near normal levels (12.4 vs. 27.5 mmol/L). No significant
changes were found in the other groups. None of the oxidative stress indices
showed significant changes in either the treated or untreated rats. CONCLUSION:
Nano-sized clinoptilolite exerted a hypoglycemic effect in streptozotocin-induced
diabetic rats but had no significant influence on oxidative stress markers.
PMID- 28506815
TI - Postpartum Diabetes Testing Rates after Gestational Diabetes Mellitus in Canadian
Women: A Population-Based Study.
AB - OBJECTIVES: We assessed the rate and type of postpartum glycemic testing in women
with impaired glucose tolerance of pregnancy (IGTp) and gestational diabetes
mellitus (GDM). We examined whether the likelihood of testing was modulated by
patients' characteristics and pregnancy outcomes. METHODS: Our population-level
cohort study included data from 132,905 pregnancies between October 1, 2008, and
December 31, 2011, in Alberta, Canada. Laboratory data within 270 days before and
1 year after delivery were used to identify pregnancies involving IGTp/GDM and
postpartum glycemic testing, respectively. Logistic regression was used to
identify maternal and pregnancy factors associated with postpartum testing.
RESULTS: A total of 8,703 pregnancies were affected by IGTp (n=3669) or GDM
(n=5034) as defined by the prevailing Canadian Diabetes Association 2008 Clinical
Practice Guidelines for the Prevention and Management of Diabetes in Canada. By 1
year postpartum, 55.1% had undergone glycemic assessments. Of those, 59.7% had
had 75 g oral glucose tolerance tests, 17.4% had had glycated hemoglobin tests
without oral glucose tolerance tests and 22.9% had had only fasting or random
glucose tests. Women with IGTp or GDM, respectively, who were younger, smokers
and residing in rural areas and whose labours were not induced were less likely
to be tested postpartum. Having large for gestational age infants was also
associated with a lower likelihood of postpartum testing in women with GDM.
CONCLUSIONS: Despite a universal health-care system in Canada, many women with
IGTp or GDM do not undergo postpartum glucose testing. Maternal and pregnancy
characteristics influence postpartum testing and provide valuable information for
creating targeted strategies to improve postpartum testing in this group of high
risk women.
PMID- 28506814
TI - The Relation of Type 2 Diabetes and Breast Cancer Incidence in Asian, Hispanic
and African American Populations-A Review.
AB - In addition to rising type 2 diabetes and breast cancer incidence rates
worldwide, diabetes may also increase breast cancer risk, and the association may
vary by ethnicity. This review summarizes published data evaluating the
association between diabetes and breast cancer in women of Asian, Hispanic and
African American ancestry while considering a measure of obesity, body mass index
(BMI). Published reports were identified through a search of PubMed and previous
publications. Of 15 age-adjusted studies, 11 reported on Asian women from various
countries, 3 on Hispanics and 1 on African Americans. The studies of Asian women
described significant associations in 8 reports, with risk estimates of 1.5 to
8.4, but 3 were case-control studies and 6 did not adjust for BMI. The 3 case
control studies of Hispanic people included BMI, but only 1 detected a weak
association between diabetes and breast cancer risk and was limited to
postmenopausal women. The only study of African American women was a prospective
cohort, and it showed no significant association between diabetes and breast
cancer. In contrast to a 10% to 20% higher risk for breast cancer associated with
diabetes reported for Caucasian women, there is little evidence for an
association in Hispanics and African Americans. Although several studies of Asian
women included in our review reported a higher risk for breast cancer with
diabetes, methodologic shortcomings, such as lack of adjustment for obesity, use
of a general population as controls, case-control design and small sample sizes,
raise questions about the validity of the findings.
PMID- 28506817
TI - In vitro CYP-mediated drug metabolism in the zebrafish (embryo) using human
reference compounds.
AB - The increasing use of zebrafish embryos as an alternative model for toxicological
and pharmacological studies necessitates a better understanding of xenobiotic
biotransformation in this species. As cytochrome P450 enzymes (CYPs) play an
essential role in this process, in vitro drug metabolism of four human CYP
specific substrates, i.e. dextromethorphan (DXM), diclofenac (DIC), testosterone
(TST) and midazolam (MDZ) was investigated in adult male and female zebrafish,
and in zebrafish embryos and larvae up to 120hours post-fertilization. Substrate
depletion and production of their respective metabolites were measured using
tandem quadrupole UPLC-MS/MS. Human liver microsomes were used as positive
control. Adult zebrafish produced the two major human metabolites of DIC and DXM.
For DIC the metabolite ratio was similar to that in man, whereas it was different
for DXM. For TST, the major human metabolite could not be detected and MDZ was
not metabolized. No sex-related differences were detected, except for the higher
TST depletion rate in adult females. Zebrafish embryos and larvae showed no or
only low biotransformation capacity. In conclusion, in vitro CYP-mediated drug
metabolism in adult zebrafish shows differences compared to man and appears to be
lacking in the early zebrafish life stages. As CYP-mediated drug metabolism in
zebrafish may not be predictive for the one in man, we recommend including the
zebrafish in metabolic stability testing of new compounds when considering non
clinical species for human risk assessment.
PMID- 28506818
TI - Measuring inhibition of monoamine reuptake transporters by new psychoactive
substances (NPS) in real-time using a high-throughput, fluorescence-based assay.
AB - The prevalence and use of new psychoactive substances (NPS) is increasing and
currently over 600 NPS exist. Many illicit drugs and NPS increase brain monoamine
levels by inhibition and/or reversal of monoamine reuptake transporters (DAT, NET
and SERT). This is often investigated using labor-intensive, radiometric endpoint
measurements. We investigated the applicability of a novel and innovative assay
that is based on a fluorescent monoamine mimicking substrate. DAT, NET or SERT
expressing human embryonic kidney (HEK293) cells were exposed to common drugs
(cocaine, dl-amphetamine or MDMA), NPS (4-fluoroamphetamine, PMMA, alpha-PVP, 5
APB, 2C-B, 25B-NBOMe, 25I-NBOMe or methoxetamine) or the antidepressant
fluoxetine. We demonstrate that this fluorescent microplate reader-based assay
detects inhibition of different transporters by various drugs and discriminates
between drugs. Most IC50 values were in line with previous results from
radiometric assays and within estimated human brain concentrations. However,
phenethylamines showed higher IC50 values on hSERT, possibly due to experimental
differences. Compared to radiometric assays, this high-throughput fluorescent
assay is uncomplicated, can measure at physiological conditions, requires no
specific facilities and allows for kinetic measurements, enabling detection of
transient effects. This assay is therefore a good alternative for radiometric
assays to investigate effects of illicit drugs and NPS on monoamine reuptake
transporters.
PMID- 28506816
TI - Ghrelin suppresses cholecystokinin (CCK), peptide YY (PYY) and glucagon-like
peptide-1 (GLP-1) in the intestine, and attenuates the anorectic effects of CCK,
PYY and GLP-1 in goldfish (Carassius auratus).
AB - Ghrelin is an important gut-derived hormone with an appetite stimulatory role,
while most of the intestinal hormones, including cholecystokinin (CCK), peptide
YY (PYY) and glucagon-like peptide-1 (GLP-1), are appetite-inhibitors. Whether
these important peptides with opposing roles on food intake interact to regulate
energy balance in fish is currently unknown. The aim of this study was to
characterize the putative crosstalk between ghrelin and CCK, PYY and GLP-1 in
goldfish (Carassius auratus). We first determined the localization of CCK, PYY
and GLP-1 in relation to ghrelin and its main receptor GHS-R1a (growth hormone
secretagogue 1a) in the goldfish intestine by immunohistochemistry.
Colocalization of ghrelin/GHS-R1a and CCK/PYY/GLP-1 was found primarily in the
luminal border of the intestinal mucosa. In an intestinal explant culture, a
significant decrease in prepro-cck, prepro-pyy and proglucagon transcript levels
was observed after 60min of incubation with ghrelin, which was abolished by
preincubation with the GHS-R1a ghrelin receptor antagonist [D-Lys3]-GHRP-6
(except for proglucagon). The protein expression of PYY and GLP-1 was also
downregulated by ghrelin. Finally, intraperitoneal co-administration of CCK, PYY
or GLP-1 with ghrelin results in no modification of food intake in goldfish.
Overall, results of the present study show for the first time in fish that
ghrelin exerts repressive effects on enteric anorexigens. It is likely that these
interactions mediate the stimulatory effects of ghrelin on feeding and metabolism
in fish.
PMID- 28506819
TI - Prediction of delivery of organic aerosols onto air-liquid interface cells in
vitro using an electrostatic precipitator.
AB - To better characterize biological responses to atmospheric organic aerosols, the
efficient delivery of aerosol to in vitro lung cells is necessary. In this study,
chamber generated secondary organic aerosol (SOA) entered the commercialized
exposure chamber (CULTEX(r) Radial Flow System Compact) where it interfaced with
an electrostatic precipitator (ESP) (CULTEX(r) Electrical Deposition Device) and
then deposited on a particle collection plate. This plate contained human lung
cells (BEAS-2B) that were cultured on a membrane insert to produce an air-liquid
interface (ALI). To augment in vitro assessment using the ESP exposure device,
the particle dose was predicted for various sampling parameters such as particle
size, ESP deposition voltage, and sampling flowrate. The dose model was evaluated
against the experimental measured mass of collected airborne particles. The high
flowrate used in this study increased aerosol dose but failed to achieve cell
stability. For example, RNA in the ALI BEAS-2B cells in vitro was stable at
0.15L/minute but decayed at high flowrates. The ESP device and the resulting
model were applied to in vitro studies (i.e., viability and IL-8 expression) of
toluene SOA using ALI BEAS-2B cells with a flowrate of 0.15L/minute, and no
cellular RNA decay occurred.
PMID- 28506820
TI - Seasonal variation of hospital violence, seclusion and restraint in a forensic
psychiatric hospital.
AB - Several epidemiological studies have reported seasonal patterns in both violent
and self-destructive behaviour. However, a few studies on hospital violence have
found contradictory results. The aim of this study was to investigate whether
there was any seasonal variation of violence in a forensic psychiatric hospital
providing care for persons suffering from psychotic disorders and violent or self
destructive behaviour. Seasonal variation of the prevalence of seclusion and
restraint was also investigated. Reports of violent incidents and seclusion and
restraint statistics from between 2007 and 2012 were examined with Poisson
regression analysis. There was significant variation in the prevalence of
seclusion and restraint between months (p<0.001), and between seasons (p<0.001).
Monthly prevalence of seclusion and restraint was the lowest in January compared
to other months. In comparison, the prevalence of seclusion and restraint was
lower in winter than in other seasons. In a hospital with persons suffering from
psychotic disorders, no significant variation of violence or self-destructive
behaviour was found, similarly as in the society. By contrast, the prevalence of
seclusion and restraint showed marked seasonality. Variation in the prevalence of
seclusion and restraint was not consistent with the variance in violence, which
implies that the use of coercive measures is related to seasonal variation among
staff.
PMID- 28506821
TI - Development of a bioassay as a measure of drozitumab-mediated apoptosis induced
by soluble Fc gamma receptors.
AB - Drozitumab is an agonistic therapeutic monoclonal antibody (mAb) against the pro
apoptotic death receptor 5 (DR5). In vitro cell killing assays using drozitumab
have traditionally required cross-linking with anti-Fc antibody to amplify the
pro-apoptotic signal, although drozitumab shows activity in in vivo tumor models
without artificial cross-linking. Recently it has been shown that FcgammaR
expressing cells play an important role in the activity of drozitumab by
mediating cross-linking in vivo (Wilson et al., 2011). To provide a more
biologically relevant alternative to cross-linking with anti-Fc antibody in in
vitro bioassays, methods for cross-linking with soluble FcgammaR extracellular
domain (ECD) were developed in this work. FcgammaR cross-linking methods
developed in this work were assessed in solution, bead-bound, and plate-bound
assay formats, as well as a cell-based assay format. The assays showed
reproducible drozitumab dose-response curves in the concentration range of 5
20,000ng/mL and had acceptable precision and accuracy. The assays are also able
to detect degradative changes in drozitumab samples subjected to thermal stress.
The data suggest that FcgammaR cross-linking of drozitumab is a viable
alternative to anti-Fc cross-linking of drozitumab to measure effector mediated
apoptosis of drozitumab in vitro.
PMID- 28506822
TI - The effect of prophylactic vertebroplasty on the incidence of proximal junctional
kyphosis and proximal junctional failure following posterior spinal fusion in
adult spinal deformity: a 5-year follow-up study.
AB - BACKGROUND CONTEXT: The incidence of proximal junctional kyphosis (PJK) ranges
from 5% to 46% following adult spinal deformity surgery. Approximately 66% to 76%
of PJK occurs within 3 months of surgery. A subset of these patients, reportedly
26% to 47%, develop proximal junctional failure (PJF) within 6 months
postoperatively. To date, there are no studies evaluating the impact of
prophylactic vertebroplasty on PJK and PJF incidence at long-term follow-up.
PURPOSE: The purpose of this study is to evaluate the long-term radiographic and
clinical outcomes, and incidence of PJK and PJF, after prophylactic
vertebroplasty for long-segment thoracolumbar posterior spinal fusion (PSF).
STUDY DESIGN: This is a prospective cohort study. PATIENT SAMPLE: Thirty-nine
patients, of whom 87% were female, who underwent two-level prophylactic
vertebroplasty at the upper instrumented and supra-adjacent vertebrae at the time
of index PSF were included in this study. OUTCOME MEASURES: Clinical outcomes
were assessed using the Scoliosis Research Society-22 (SRS-22), and Short-Form
(SF) 36 questionnaires, and the Oswestry Disability Index (ODI). Radiographic
parameters including PJK angle, and coronal and sagittal alignment, were
calculated, along with relevant perioperative complications and revision rates.
METHODS: Of the 41 patients who received two-level prophylactic vertebroplasty at
the upper instrumented and supra-adjacent vertebrae at the time of index PSF, and
comprised a cohort with previously published 2-year follow-up data, 39 (95%)
completed 5-year follow-up (average: 67.6 months). Proximal junctional kyphosis
was defined as a change in the PJK angle >=10 degrees between the immediate
postoperative and final follow-up radiograph. Proximal junctional failure was
defined as acute proximal junctional fracture, fixation failure, or kyphosis
requiring extension of fusion within the first 6 months postoperatively. RESULTS:
Thirty-nine patients with a mean age of 65.6 (41-87) years were included in this
study. Of the 39 patients, 28.2% developed PJK (11: 7.7% at 2 years, 20.5%
between 2 and 5 years), and 5.1% developed acute PJF. Two of the 11 PJK patients
required revision for progressive worsening of the PJK. There were no proximal
junctional fractures. There was no significant difference in preoperative,
immediate postoperative, and final follow-up measurements of thoracic kyphosis,
lumbar lordosis, and coronal or sagittal alignment between patients who developed
PJK, PJF, or neither (p>.05). There was no significant difference in ODI, SRS-22,
or SF-36 scores between those with and without PJK or PJF (p>.05). CONCLUSIONS:
This long-term follow-up demonstrates that prophylactic vertebroplasty may
minimize the risk for junctional failure in the early postoperative period.
However, it does not appear to decrease the incidence of PJK at 5 years.
PMID- 28506823
TI - Hyperammonemia compromises glutamate metabolism and reduces BDNF in the rat
hippocampus.
AB - Ammonia is putatively the major toxin associated with hepatic encephalopathy
(HE), a neuropsychiatric manifestation that results in cognitive impairment, poor
concentration and psychomotor alterations. The hippocampus, a brain region
involved in cognitive impairment and depressive behavior, has been studied less
than neocortical regions. Herein, we investigated hippocampal astrocyte
parameters in a hyperammonemic model without hepatic lesion and in acute
hippocampal slices exposed to ammonia. We also measured hippocampal BDNF, a
neurotrophin commonly related to synaptic plasticity and cognitive deficit, and
peripheral S100B protein, used as a marker for brain damage. Hyperammonemia
directly impaired astrocyte function, inducing a decrease in glutamate uptake and
in the activity of glutamine synthetase, in turn altering the glutamine-glutamate
cycle, glutamatergic neurotransmission and ammonia detoxification itself.
Hippocampal BDNF was reduced in hyperammonemic rats via a mechanism that may
involve astrocyte production, since the same effect was observed in astrocyte
cultures exposed to ammonia. Ammonia induced a significant increase in S100B
secretion in cultured astrocytes; however, no significant changes were observed
in the serum or in cerebrospinal fluid. Data demonstrating hippocampal
vulnerability to ammonia toxicity, particularly due to reduced glutamate uptake
activity and BDNF content, contribute to our understanding of the
neuropsychiatric alterations in HE.
PMID- 28506824
TI - Hypoxia and nicotine effects on Pituitary adenylate cyclase activating
polypeptide (PACAP) and its receptor 1 (PAC1) in the developing piglet brainstem.
AB - Pituitary adenylate cyclase activating polypeptide (PACAP) and its cognate
receptor 1 (PAC1), have been implicated in the pathophysiology of the Sudden
Infant Death Syndrome (SIDS). Two main risk factors for SIDS are prone sleeping
and cigarette smoke exposure. Using piglet models of these risk factors,
intermittent hypercapnic hypoxia (IHH-mimicking rebreathing in prone position)
and nicotine (main reinforcing element of cigarettes), this study aimed to
determine their effects on PACAP and PAC1 protein expression in the medulla. IHH
was delivered for 1 (n=7), 2 (n=6), 3 (n=6) and 4 (n=7) days prior to euthanasia
at 13-14days of age, while nicotine (n=7) was continuous for the first 14days of
life. An additional group of combined nicotine and 1day IHH (1DIHH) was studied
to determine the combined effects of the risk factors. Changes in expression were
seen after the acute 1DIHH exposure (none after repeated daily exposures) and
included a decrease in PACAP in the dorsal motor nucleus of vagus (DMNV;
p=0.024), nucleus of the solitary tract (NTS; p=0.024) and the gracile nucleus
(GRAC; p=0.001), and a decrease in PAC1 in the NTS (p=0.01). No PACAP change was
noted in the nicotine-exposed piglets, however, a decrease in PAC1 was found in
the DMNV (p=0.02). IHH exposure in piglets with pre-exposure to nicotine led to a
significant decrease in PACAP in the Grac (p=0.04) but had no effect on PAC1.
These findings show for the first time, the vulnerability of PACAP in the
brainstem during early development to an acute hypercapnic hypoxic exposure and
that those effects are greater than from nicotine exposure.
PMID- 28506825
TI - Multiple drug resistance in Haemophilus influenzae isolated from patients in
Bangkok, Thailand.
PMID- 28506826
TI - An X-chromosome linked mouse model (Ndufa1S55A) for systemic partial Complex I
deficiency for studying predisposition to neurodegeneration and other diseases.
AB - The respiratory chain Complex I deficiencies are the most common cause of
mitochondrial diseases. Complex I biogenesis is controlled by 58 genes and at
least 47 of these cause mitochondrial disease in humans. Two of these are X
chromosome linked nuclear (nDNA) genes (NDUFA1 and NDUFB11), and 7 are
mitochondrial (mtDNA, MT-ND1-6, -4L) genes, which may be responsible for sex
dependent variation in the presentation of mitochondrial diseases. In this study,
we describe an X-chromosome linked mouse model (Ndufa1S55A) for systemic partial
Complex I deficiency. By homologous recombination, a point mutation T > G within
55th codon of the Ndufa1 gene was introduced. The resulting allele Ndufa1S55A
introduced systemic serine-55-alanine (S55A) mutation within the MWFE protein,
which is essential for Complex I assembly and stability. The S55A mutation caused
systemic partial Complex I deficiency of ~50% in both sexes. The mutant males
(Ndufa1S55A/Y) displayed reduced respiratory exchange ratio (RER) and produced
less body heat. They were also hypoactive and ate less. They showed age-dependent
Purkinje neurons degeneration. Metabolic profiling of brain, liver and serum from
males showed reduced heme levels in mutants, which correlated with altered
expressions of Fech and Hmox1 mRNAs in tissues. This is the first genuine X
chromosome linked mouse model for systemic partial Complex I deficiency, which
shows age-dependent neurodegeneration. The effect of Complex I deficiency on
survival patterns of males vs. females was different. We believe this model will
be very useful for studying sex-dependent predisposition to both spontaneous and
stress-induced neurodegeneration, cancer, diabetes and other diseases.
PMID- 28506827
TI - How tumor growth can be influenced by delayed interactions between cancer cells
and the microenvironment?
AB - Although recent advances in oncology emphasized the role of microenvironment in
tumor growth, the role of delays for modeling tumor growth is still uncertain. In
this paper, we considered a model, describing the interactions of tumor cells
with their microenvironment made of immune cells and host cells, in which we
inserted, as suggested by the clinicians, two time delays, one in the
interactions between tumor cells and immune cells and, one in the action of
immune cells on tumor cells. We showed analytically that the singular point
associated with the co-existence of the three cell populations loses its
stability via a Hopf bifurcation. We analytically calculated a range of the
delays over which tumor cells are inhibited by immune cells and over which a
period-1 limit cycle induced by this Hopf bifurcation is observed. By using a
global modeling technique, we investigated how the dynamics observed with two
delays can be reproduced by a similar model without delays. The effects of these
two delays were thus interpreted in terms of interactions between the cell
populations.
PMID- 28506828
TI - Stringency of bacterial prolipoprotein signal peptidase (LspA) in recognition of
signal peptides - Structure-function correlation.
AB - Bacterial lipid modification of proteins is an essential post-translational event
committed by Phosphatidylglycerol: prolipoprotein diacylglyceryl transferase
(Lgt) by catalysing diacyglyceryl transfer from Phosphatidylglycerol to cysteine
present in the characteristic 'lipobox' ([LVI] (-3) [ASTVI] (-2) [GAS] (-1) C
(+1)) of prolipoprotein signal peptides. This is then followed by the cleavage of
the signal peptide by lipoprotein-specific signal peptidase (LspA). It had been
known for long that threonine at the -1 position allows diacylglyceryl
modification by Lgt, but not signal peptide cleavage by LspA. We have addressed
this unexplained stringency by computational analysis of the recently published
3D structure of LspA with its competitive inhibitor as well as transition state
analogue, globomycin using PyMoL viewing tool and VADAR (Volume, Area, Dihedral
Angle Reporter) web server. The propensity to form hydrogen bond (2.9a) between
the hydroxyl group of threonine (not possible with serine) and the NH of the
lipid-modified cysteine, possible only in the transition state, will prevent the
protonation of NH of the leaving peptide and therefore its cleavage. This
knowledge could be useful for designing inhibitors of this essential pathway in
bacteria or for engineering LspA.
PMID- 28506829
TI - An asymmetric dimeric structure of TrmJ tRNA methyltransferase from Zymomonas
mobilis with a flexible C-terminal dimer.
AB - The tRNA methyltransferase J (TrmJ) and D (TrmD) catalyze the transferring
reaction of a methyl group to the tRNA anticodon loop. They commonly have the N
terminal domain (NTD) and the C-terminal domain (CTD). Whereas two monomeric CTDs
symmetrically interact with a dimeric NTD in TrmD, a CTD dimer has exhibited an
asymmetric interaction with the NTD dimer in the presence of a product. The
elucidated apo-structure of the full-length TrmJ from Zymomonas mobilis ZM4 shows
a dimeric CTD that asymmetrically interacts with the NTD dimer, thereby
distributing non-symmetrical potential charge on the both side of the protein
surface. Comparison with the product-bound structures reveals a local re
orientation of the two arginine-containing loop at the active site, which
interacts with the product. Further, the CTD dimers have diverse orientations
compared to the NTD dimers, suggesting their flexibility. These data indicate
that an asymmetric interaction between the NTD dimer and the CTD dimer is a
common structural feature among TrmJ proteins, regardless of the presence of a
substrate or a product.
PMID- 28506830
TI - Antibiotics-induced gut microbiota dysbiosis promotes tumor initiation via
affecting APC-Th1 development in mice.
AB - Gut microbiota is critical for maintaining body immune homeostasis and thus
affects tumor growth and therapeutic efficiency. Here, we investigated the link
between microbiota and tumorgenesis in a mice model of subcutaneous melanoma cell
transplantation, and explored the underlying mechanism. We found disruption of
gut microbiota by pretreating mice with antibiotics promote tumor growth and
remodeling the immune compartment within the primary tumor. Indeed, gut microbial
dysbiosis reduced the infiltrated mature antigen-presenting cells of tumor,
together with lower levels of co-stimulators, such as CD80, CD86 and MHCII, as
well as defective Th1 cytokines, including IFNgamma, TNFalpha, IL12p40, and
IL12p35. Meantime, splenic APCs displayed blunted ability in triggering T cell
proliferation and IFNgamma secretion. However, oral administration of LPS
restored the immune surveillance effects and thus inhibited tumor growth in the
antibiotics induced gut microbiota dysbiosis group. Taken together, these data
highly supported that antibiotics induced gut microbiota dysbiosis promotes tumor
initiation, while LPS supplementation would restore the effective immune
surveillance and repress tumor initiation.
PMID- 28506831
TI - Alpha B-crystallin promotes the invasion and metastasis of colorectal cancer via
epithelial-mesenchymal transition.
AB - Alpha B-crystallin (CRYAB, HSPB5) is a protein that was first discovered in the
lens of the eye. It is a member of the small heat-shock protein family (sHsps).
CRYAB functions primarily as a molecular chaperone to prevent the aggregation and
degradation of damaged unfolded proteins due to cellular damage resulting from
heat shock, radiation, oxidative stress, and other insults, thereby promoting
cell survival and preventing apoptosis. In recent years, the role of CRYAB in
tumorigenesis, tumor invasion, and metastasis has received increasing attention.
CRYAB is highly expressed in a variety of cancers, including breast cancer, head
and neck cancer, and kidney cancer, and is likely associated with the prognosis
of cancer. However, few studies have examined CRYAB in colorectal cancer (CRC).
To study the effect of CRYAB on CRC, we transfected the CRC cell line SW480,
which expresses high levels of CRYAB, with a lentiviral vector that inhibits
CRYAB expression. The messenger RNA (mRNA) and protein expression of CRYAB was
examined in the transfected SW480 cells (Si-CRYAB) using quantitative real-time
polymerase chain reaction (qPCR) and Western blotting (WB) assays. Moreover, a
growth curve was plotted to examine the proliferation of Si-CRYAB cells, and
transwell assays were used to examine the migration of Si-CRYAB cells. Apoptosis
and the cell cycle were examined in Si-CRYAB cells using flow cytometry (FCM),
and the tumorigenic capability of Si-CRYAB cells was assessed in a nude mouse
tumor model. Immunohistochemistry (IHC) was employed to examine CRYAB protein
expression and the markers of epithelial-mesenchymal transition (EMT), such as E
cadherin, fibronectin, vimentin, and slug, in tumor tissues from nude mice and
clinical invasive CRC and hepatic metastasis specimens. The qPCR and WB results
showed that CRYAB was downregulated at the protein and mRNA level in Si-CRYAB
cells, and the growth curve indicated that the proliferation of Si-CRYAB cells
was reduced. Moreover, Si-CRYAB cells exhibited reduced migration capability in
the transwell assay as well as increased apoptosis and G1 arrest in the FCM
assay. The tumorigenesis study in nude mice showed that Si-CRYAB cells formed
smaller tumors, indicating decreased tumorigenic capability. IHC results showed
reduced CRYAB expression and lower levels of EMT in Si-CRYAB cells, whereas
clinical specimens of invasive CRC and hepatic metastases exhibited elevated
CRYAB expression and enhanced levels of EMT. These results demonstrated that
CRYAB promoted the invasion and metastasis of CRC tumor cells via EMT.
PMID- 28506832
TI - Regarding "Proximal Tubal Patency Demonstrated Through Air Infusion During
Flexible Office Hysteroscopy Is Predictive of Whole Tubal Patency".
PMID- 28506833
TI - Response to Letter to the Editor: Author's Reply.
PMID- 28506834
TI - Safety evaluation of dermal exposure to phthalates: Metabolism-dependent
percutaneous absorption.
AB - Phthalates, known as reproductive toxicants and endocrine disruptors, are widely
used as plasticizers in polyvinyl chloride products. The present study was
conducted for risk identification of dermal exposure to phthalates. When dibutyl
phthalate was applied to the skin of hairless rats and humans, only monobutyl
phthalate appeared through the skin, and the permeability of the skin was higher
than that after the application of the monoester directly. The inhibition of skin
esterases made the skin impermeable to the metabolite following dermal exposure
to dibutyl ester, whereas removal of the stratum corneum from the skin did not
change the skin permeation behavior. Similar phenomena were observed for benzyl
butyl phthalate. The skin permeability of monobenzyl phthalate was higher than
that of monobutyl phthalate in humans, although the reverse was observed in rats.
Species difference in skin permeation profile corresponded to the esterase
activity of the skin homogenate. Di(2-ethylhexyl) phthalate, which was not
metabolized by esterases in the skin, was not transported across the skin. These
results suggest that highly lipophilic phthalates may be transported easily
across the stratum corneum lipids. The water-rich viable layer may become
permeable to these phthalates by their metabolism into monoesters, which are
relatively hydrophilic. Skin metabolism is essential to the percutaneous
absorption of phthalates. Because esterase activity has large inter-individual
differences, further study will be needed for individual risk identification of
dermal exposure to phthalates.
PMID- 28506835
TI - Impact of common clandestine structural modifications on synthetic cathinone
"bath salt" pharmacokinetics.
AB - Since 2009, the synthetic cathinones ("bath salts") have risen in popularity as
drugs of abuse. However, there are a paucity of studies that have determined the
impact of functional group modifications in the synthetic cathinone chemical
structures on plasma and central nervous system (CNS) pharmacokinetics. In the
present study, we investigated the in vivo plasma and CNS pharmacokinetics of
three synthetic cathinones whose structures differ by lengthening of the alpha
alkyl chain: methylone (-CH3), butylone (-CH2CH3), and pentylone (-CH2CH2CH3).
Male Sprague-Dawley rats were treated with a 20mg/kg subcutaneous dose of the
individual synthetic cathinone. Blood samples were obtained at specific times
from a jugular vein cannula over an 8hour period. Over a separate three-hour
period, CNS samples were obtained using a microdialysis cannula surgically
implanted into the lateral ventricle. In the plasma, pentylone, with the longest
alpha-alkyl chain, displayed the highest Cmax and AUC0-infinity, and the longest
t1/2. Decreasing the alpha-alkyl chain length as in butylone and methylone
significantly decreased the Cmax, AUC0-infinity, and t1/2. The plasma
pharmacokinetic values are consistent with the greater lipophilicity associated
with alpha-alkyl side chain lengthening. Conversely, in the CNS, methylone and
butylone displayed higher Cmax and AUC0-infinity values than pentylone. These
contrary findings in the CNS and plasma demonstrate that lengthening of the alpha
alkyl chain of methylone, butylone, and pentylone yields differential
pharmacokinetic properties in the CNS as compared to the plasma.
PMID- 28506836
TI - A comprehensive review of metal-induced cellular transformation studies.
AB - In vitro transformation assays not only serve practical purposes in screening for
potential carcinogenic substances in food, drug, and cosmetic industries, but
more importantly, they provide a means of understanding the critical biological
processes behind in vivo cancer development. In resemblance to cancer cells in
vivo, successfully transformed cells display loss of contact inhibition, gain of
anchorage independent growth, resistant to proper cell cycle regulation such as
apoptosis, faster proliferation rate, potential for cellular invasion, and
ability to form tumors in experimental animals. Cells purposely transformed using
metal exposures enable researchers to examine molecular changes, dissect various
stages of tumor formation, and ultimately elucidate metal induced cancer mode of
action. For practical purposes, this review specifically focuses on studies
incorporating As-, Cd-, Cr-, and Ni-induced cell transformation. Through
investigating and comparing an extensive list of studies using various methods of
metal-induced transformation, this review serves to bridge an information gap and
provide a guide for avoiding procedural discrepancies as well as maximizing
experimental efficiency.
PMID- 28506837
TI - The roles of actin cytoskeleton and actin-associated protein Crn1p in trap
formation of Arthrobotrys oligospora.
AB - Nematode-trapping fungi include a variety of species capable of generating
specific trapping devices to capture nematodes and the production of devices is
also an indicator of a switch from saprophytic to predacious lifestyles. Traps
are developed from vegetative mycelia, but they are quite different from hyphae
in both morphological and physiological characteristics. Therefore, the molecular
mechanisms underlying their formation have attracted much attention. In this
investigation, Arthrobotrys oligospora, a nematode-trapping fungus, has three
dimensional networks and genomics and proteomics were recently performed, so as
to reveal the relationship between actin cytoskeleton and trap formation. Both
actin staining via FITC-phalloidin and treatment of actin polymerization
inhibitor Lat-B illustrated that the actin cytoskeleton played an important role
in trap development. Furthermore, absence of the conserved actin-associated
protein Crn1p caused a structural defect of traps and failure to infect
nematodes. It was observed that mutant Deltacrn1 represented a reduced number of
rings and a lower complexity of three-dimensional networks, likely due to the
disturbance of actin branching. Collectively, our study confirmed the involvement
of the actin cytoskeleton as well as the conserved actin-associated protein Crn1p
in trap formation. It further suggested the manners in which Crn1p influences the
development of three-dimensional networks in A. oligospora.
PMID- 28506838
TI - Phylogenomic analysis of the complete sequence of a gastroenteritis-associated
cetacean adenovirus (bottlenose dolphin adenovirus 1) reveals a high degree of
genetic divergence.
AB - Adenoviruses are common pathogens in vertebrates, infecting a wide range of
hosts, but only having rarely been detected and correlated with disease in
cetaceans. This article describes the first complete genomic sequence of a
cetacean adenovirus, bottlenose dolphin adenovirus 1 (BdAdV-1), detected in
captive bottlenose dolphin population (Tursiops truncatus) suffering from self
limiting gastroenteritis. The complete genome sequence of BdAdV-1 was recovered
from data generated by high-throughput sequencing and validated by Sanger
sequencing. The genome is 34,080bp long and has 220 nucleotides long inverted
terminal repeats. A total of 29 coding sequences were identified, 26 of which
were functionally annotated. Among the unusual features of this genome is a
remarkably long 4380bp E3 ORF1, that displays no sequence homology with the
corresponding E3 regions of other adenoviruses. In addition, the fiber protein
only has 26% identity with fiber proteins described in other adenoviruses. Three
hypothetical proteins were predicted. The phylogenetic analysis indicates that
the closest known relative to BdAdV-1 is an adenovirus detected in bottlenose
dolphin (KR024710), with an amino acid sequence identity between 36 and 79%
depending on the protein. Based on the phylogenic analysis, the BdAdV-1 appears
to have co-evolved with its host. The results indicate that BdAdV-1 belongs to
the Mastadenovirus genus of the Adenoviridae family, however, it is clearly
different from other adenoviruses, especially in the 3'-end of the viral genome.
The high degree of sequence divergence suggests that BdAdV-1 should be considered
as a novel species in the Mastadenovirus genus. The study also demonstrates the
usefulness of high-throughput sequencing to obtain full-length genomes of
genetically divergent viruses.
PMID- 28506840
TI - Characterization of genome segments 2, 3 and 6 of epizootic hemorrhagic disease
virus strains isolated in Japan in 1985-2013: Identification of their serotypes
and geographical genetic types.
AB - We characterized genome segments 2, 3 and 6 (Seg-2, Seg-3 and Seg-6) of 11
Japanese strains of epizootic hemorrhagic disease (EHD) virus (EHDV) isolated in
1985-2013. The Japanese strains were divisible into two groups based on
phylogenetic analyses of the nucleotide sequences of Seg-2 and Seg-6. In both of
the phylogenetic trees based on Seg-2 and Seg-6, seven of the 11 Japanese strains
were grouped together with EHDV-2 and EHDV-7 strains, and the other four Japanese
strains were grouped with EHDV-1 strains. The phylogenetic analysis of Seg-2
among EHDV strains identified 10 of the 11 Japanese strains as EHDV-1, EHDV-2 or
EHDV-7. The other Japanese strain, ON-4/B/98, isolated from an asymptomatic cow
in 1998 was in the same group as the EHDV-2 and EHDV-7 strains in the
phylogenetic trees based on Seg-2 and Seg-6, but the results suggested that the
strain belongs to another serotype. We thus conducted a serum neutralization test
to identify that serotype by using anti-EHDV-2 and anti-EHDV-7 rabbit sera. We
observed that the ON-4/B/98 strain was not sufficiently neutralized by any of the
antisera, which suggests that the strain could be assigned into a new serotype,
tentatively named 'EHDV-10.' Sequences of Seg-3 were also determined, and all of
the Japanese strains were grouped together with Australian strains, suggesting
that the Japanese strains are a part of EHDV distributed in the Asia-Pacific
region. The data obtained herein would be beneficial for the diagnosis and
prevention of EHD in Japan and neighboring countries.
PMID- 28506839
TI - Evolutionary relationships among protein lysine deacetylases of parasites causing
neglected diseases.
AB - The availability of the genomic data of diverse parasites provides an opportunity
to identify new drug candidates against neglected tropical diseases affecting
people worldwide. Histone modifying enzymes (HMEs) are potential candidates since
they play key roles in the regulation of chromatin modifications, thus globally
regulating gene expression. Furthermore, aberrant epigenetic states are often
associated with human diseases, leading to great interest in HMEs as therapeutic
targets. Our work focused on two families of protein lysine deacetylases (HDACs
and sirtuins). First, we identified potential homologues in the predicted
proteomes of selected taxa by using hidden Markov model profiles. Then, we
reconstructed the evolutionary relationships of protein sequences by Bayesian
inference and maximum likelihood method. In addition, we constructed homology
models for five parasite HDACs to provide information for experimental validation
and structure-based optimization of inhibitors. Our results showed that parasite
genomes code for diverse HDACs and sirtuins. The evolutionary pattern of protein
deacetylases with additional experimental data points to these enzymes as common
drug targets among parasites. This work has improved the functional annotation of
approximately 63% HDACs and 51% sirtuins in the selected taxa providing insights
for experimental design. Homology models pointed out structural conservation and
differences among parasite and human homologues and highlight potential
candidates for further inhibitor development. Some of these parasite proteins are
undergoing RNA interference or knockout analyses to validate the function of
their corresponding genes. In the future, we will investigate the main functions
performed by these proteins, related phenotypes, and their potential as
therapeutic targets.
PMID- 28506841
TI - Definition of a Critical Size Osteochondral Knee Defect and its Negative Effect
on the Surrounding Articular Cartilage in the Rat.
AB - BACKGROUND: Joint trauma is predisposing to the incidence of osteoarthritis (OA)
of the knee. There is a limited knowledge on the impact of posttraumatic
osteochondral defects on the whole joint. This study was designed to define a
critical size osteochondral defect in the knee of rats and to investigate a
possible association between osteochondral defects and degeneration of the
surrounding joint surface. METHODS: Cylindrical osteochondral defects of
different sizes were created in the knee joint of rats. The natural course of
these lesions was studied by macroscopic observation, histology, and
immunohistochemistry. Gene expression of the articular cartilage surrounding the
defects in vivo and of articular chondrocytes cultured in vitro in IL1beta and
fibroblast growth factor 2 (FGF2) supplemented media was evaluated by
quantitative polymerase chain reaction (qPCR). RESULTS: In defects of 0.9 mm
diameter, spontaneous joint surface healing was observed but also upward
advancing of the subchondral bone plate at 16 weeks. Larger 1.4 mm diameter
defects were critical size, not resulting in successful healing at any time
point. Importantly, the articular cartilage surrounding the defects expressed
FGF2 and IL1beta, but not ACAN and Col2. Chondrocytes cultured in IL1beta and
FGF2 supplemented media lost the natural fibroblast growth factor receptors -
FGFr1/FGFr3 balance and showed decreased viability. CONCLUSIONS: A critical size
osteochondral defect was defined as 1.4 mm in diameter in rat. Subchondral bone
plate advancement occured rapidly. The articular cartilage surrounding
osteochondral defects showed catabolic activity with expression of IL1beta, FGF2
and a disturbed FGFr1/FGFr3 balance, potentially initiating a process of early
osteoarthritic disease.
PMID- 28506842
TI - Diagnostic and prognostic value of delayed Gadolinium Enhanced Magnetic Resonance
Imaging of Cartilage (dGEMRIC) in early osteoarthritis of the hip.
AB - BACKGROUND: Delayed Gadolinium Enhanced Magnetic Resonance Imaging of Cartilage
(dGEMRIC) can detect glycosaminoglycan loss in the acetabular cartilage of
asymptomatic individuals with cam morphology. The aims of this study were to
explore the relationship between cam morphology and dGEMRIC values, and to
explore whether baseline dGEMRIC can predict the development of radiographic hip
osteoarthritis. METHODS: Prospective cohort (SibKids) study with clinical,
radiographic, and MRI assessment at baseline and five-year follow-up (n = 34).
The dGEMRIC values of cartilage regions were correlated with measures of cam
morphology. Receiver operating characteristic (ROC) analysis was applied to
baseline variables to predict radiographic loss of joint space width. RESULTS:
Superolateral acetabular cartilage dGEMRIC values were significantly lower in
participants with cam morphology (P < 0.001), defined as an alpha angle greater
than 60 degrees . There was a negative correlation between alpha angle and the
dGEMRIC value of adjacent acetabular cartilage. This relationship was strongest
superoanteriorly (r = -0.697 P < 0.001). There was a positive correlation between
baseline dGEMRIC and the magnitude of joint space width narrowing (r = 0.398 P =
0.030). ROC analysis of combined baseline variables (positive impingement test,
alpha angle, dGEMRIC ratio) gave an Area Under the Curve (AUC) of 0.75 for
predicting joint space width narrowing greater than 0.5 mm within 5 years.
CONCLUSIONS: The size and position of cam morphology determines the severity and
location of progressive cartilage damage, supporting the biomechanical aetiology
of femoroacetabular impingement. Baseline dGEMRIC is able to predict the
development of radiographic osteoarthritis. Compositional MRI offers the
potential to identify patients who may benefit from early intervention to prevent
the development of osteoarthritis.
PMID- 28506844
TI - Proarrhythmic risk assessment using conventional and new in vitro assays.
AB - Drug-induced QT prolongation is a major safety issue in the drug discovery
process. This study was conducted to assess the electrophysiological responses of
four substances using established preclinical assays usually used in regulatory
studies (hERG channel or Purkinje fiber action potential) and a new assay (human
induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs)-field
potential). After acute exposure, moxifloxacin and dofetilide concentration
dependently decreased IKr amplitude (IC50 values: 102 MUM and 40 nM,
respectively) and lengthened action potential (100 MUM moxifloxacin: +23% and 10
nM dofetilide: +18%) and field potential (300 MUM moxifloxacin: +76% and 10 nM
dofetilide: +38%) durations. Dofetilide starting from 30 nM induced arrhythmia in
hiPSC-CMs. Overnight application of pentamidine (10 and 100 MUM) and arsenic (1
and 10 MUM) decreased IKr, whereas they were devoid of effects after acute
application. Long-term pentamidine incubation showed a time- and concentration
dependent effect on field potential duration. In conclusion, our data suggest
that hiPSC-CMs represent a fully functional cellular electrophysiology model
which may significantly improve the predictive validity of in vitro safety
studies. Thereafter, lead candidates may be further investigated in patch-clamp
assays for mechanistic studies on individual ionic channels or in a multicellular
Purkinje fiber preparation for confirmatory studies on cardiac conduction.
PMID- 28506843
TI - Longitudinal association between foot and ankle symptoms and worsening of
symptomatic radiographic knee osteoarthritis: data from the osteoarthritis
initiative.
AB - OBJECTIVE: To assess whether foot and/or ankle symptoms are associated with an
increased risk of worsening of knee pain and radiographic change in people with
knee osteoarthritis (OA). METHODS: The presence and laterality of foot/ankle
symptoms were recorded at baseline in 1368 participants from the Osteoarthritis
Initiative (OAI) with symptomatic radiographic knee OA. Knee pain severity
(measured using the Western Ontario and McMaster Universities Osteoarthritis
Index pain subscale) and minimum medial tibiofemoral joint space (minJSW) width
measured on X-ray were assessed yearly over the subsequent 4 years. Associations
between foot/ankle symptoms and worsening of (1) knee pain, and (2) both knee
pain and minJSW (i.e., symptomatic radiographic knee OA) were assessed using
logistic regression. RESULTS: Foot/ankle symptoms in either foot/ankle
significantly increased the odds of knee pain worsening (adjusted OR 1.54, 95% CI
1.25 to 1.91). Laterality analysis showed ipsilateral (adjusted OR 1.50, 95% CI
1.07 to 2.10), contralateral (adjusted OR 1.44, 95% CI 1.02 to 2.06) and
bilateral foot/ankle symptoms (adjusted OR 1.61, 95% CI 1.22 to 2.13) were all
associated with knee pain worsening in the follow up period. There was no
association between foot/ankle symptoms and worsening of symptomatic radiographic
knee OA. CONCLUSION: The presence of foot/ankle symptoms in people with
symptomatic radiographic knee OA was associated with increased risk of knee pain
worsening, but not worsening of symptomatic radiographic knee OA, over the
subsequent 4 years. Future studies should investigate whether treatment of
foot/ankle symptoms reduces the risk of knee pain worsening in people with knee
OA.
PMID- 28506846
TI - Allergen-specific immunotherapy modulates the balance of circulating Tfh and Tfr
cells.
PMID- 28506845
TI - Ex Vivo Mesenchymal Precursor Cell-Expanded Cord Blood Transplantation after
Reduced-Intensity Conditioning Regimens Improves Time to Neutrophil Recovery.
AB - We previously showed the safety of using cord blood (CB) expanded ex vivo in
cocultures with allogeneic mesenchymal precursor cells (MPC) after myeloablative
conditioning with faster recovery of neutrophils and platelets compared with
historical controls. Herein, we report the transplantation outcomes of 27
patients with hematologic cancers who received 1 CB unit expanded ex vivo with
MPCs in addition to an unmanipulated CB (MPC group) after reduced-intensity
conditioning (RIC). The results in this group were compared with 51 historical
controls who received 2 unmanipulated CB units (control group). The analyses were
stratified for 2 RIC treatment groups: (1) total body irradiation 200 cGy +
cyclophosphamide + fludarabine) (TCF), and (2) fludarabine + melphalan (FM).
Coculture of CB with MPCs led to an expansion of total nucleated cells by a
median factor of 12 and of CD34+ cells by a median factor of 49. In patients in
whom engraftment occurred, the median time to neutrophil engraftment was 12 days
in the MPC group, as compared with 16 days in controls (P = .02). The faster
neutrophil engraftment was observed in both RIC groups. The cumulative incidence
of neutrophil engraftment on day 26 was 75% with expansion versus 50% without
expansion in patients who received FM as the RIC regimen (P = .03). Incidence of
neutrophil engraftment was comparable in MPC and control groups if treated with
TCF (82% versus 79%, P = .40). Transplantation of CB units expanded with MPCs is
safe and effective with faster neutrophil engraftment even after RIC regimens.
PMID- 28506848
TI - Inflammatory marker analysis in psoriatic skin under topical phosphodiesterase 4
inhibitor treatment.
PMID- 28506847
TI - A short course of gamma-tocopherol mitigates LPS-induced inflammatory responses
in humans ex vivo.
PMID- 28506849
TI - Phase 2 to phase 3 clinical trial transitions: Reasons for success and failure in
immunologic diseases.
PMID- 28506851
TI - ImmunoCAP cellulose displays cross-reactive carbohydrate determinant (CCD)
epitopes and can cause false-positive test results in patients with high anti-CCD
IgE antibody levels.
AB - BACKGROUND: Cross-reactive carbohydrate determinants (CCDs) in plants and insect
venoms are a common cause of irrelevant positive test results during in vitro
allergy diagnosis. We observed that some CCD-positive sera show nonspecific IgE
binding even with CCD-free recombinant allergens when using the Phadia ImmunoCAP
platform. OBJECTIVE: We investigated whether cellulose used as an allergen
carrier in ImmunoCAP harbors residual N-glycans, causing nonspecific background
binding in CCD-positive sera. METHODS: IgE binding to 6 samples of blank
ImmunoCAPs coupled to either streptavidin (SA-CAP-1 or 2) or nonallergenic
maltose-binding protein (MBP; MBP-CAP-1 to 4) and binding to a panel of 4
recombinant allergens were compared in CCD-positive sera before and after
inhibition with a CCD inhibitor (MUXF3-human serum albumin). RESULTS: Of 52 CCD
positive sera (bromelain, 1.01-59.6 kilounits of antigen per liter [kUA/L])
tested on SA-CAP-1, 35 (67%) showed IgE binding of greater than 0.35 kUA/L (0.41
4.22 kUA/L). Among those with anti-CCD IgE levels of greater than 7.0 kUA/L, 90%
(26/29) were positive. IgE binding to SA-CAP-1 correlated with IgE binding to
bromelain (r = 0.68) and was completely abolished by serum preincubation with the
CCD inhibitor (n = 15). Binding scores with SA-CAP-2 and MBP-CAP-1 to MBP-CAP-4
were generally lower but strongly correlated with those of SA-CAP-1 and
bromelain. IgE reactivity of 10 CCD-positive sera (14.0-52.5 kUA/L) with the
recombinant allergens rPhl p 12, rFel d 1, rAra h 2, and rPru p 3 was positive to
at least 1 allergen in 8 of 10 (0.36-1.63 kUA/L) and borderline in 2 of 10 (0.21
0.25 kUA/L). Binding correlated with antibody binding to bromelain (r = 0.61) and
to all blank ImmunoCAPs (r > 0.90) and could be completely blocked by the CCD
inhibitor. Overall, mean background binding to cellulose CCDs corresponded to 2%
to 3% of the reactivity seen with bromelain. CONCLUSIONS: Cellulose used as a
solid-phase allergen carrier can contain varying amounts of CCDs sufficient to
cause false-positive test results up to 2 kUA/L with nonglycosylated recombinant
allergens in patients with high levels of anti-CCD IgE antibodies.
PMID- 28506852
TI - Pulmonary inflammation in patients with chronic obstructive pulmonary disease
with higher blood eosinophil counts.
PMID- 28506850
TI - Neutrophil extracellular traps are associated with disease severity and
microbiota diversity in patients with chronic obstructive pulmonary disease.
AB - BACKGROUND: Neutrophil extracellular traps (NETs) have been observed in the
airway in patients with chronic obstructive pulmonary disease (COPD), but their
clinical and pathophysiologic implications have not been defined. OBJECTIVE: We
sought to determine whether NETs are associated with disease severity in patients
with COPD and how they are associated with microbiota composition and airway
neutrophil function. METHODS: NET protein complexes (DNA-elastase and histone
elastase complexes), cell-free DNA, and neutrophil biomarkers were quantified in
soluble sputum and serum from patients with COPD during periods of disease
stability and during exacerbations and compared with clinical measures of disease
severity and the sputum microbiome. Peripheral blood and airway neutrophil
function were evaluated by means of flow cytometry ex vivo and experimentally
after stimulation of NET formation. RESULTS: Sputum NET complexes were associated
with the severity of COPD evaluated by using the composite Global Initiative for
Obstructive Lung Disease scale (P < .0001). This relationship was due to modest
correlations between NET complexes and FEV1, symptoms evaluated by using the COPD
assessment test, and higher levels of NET complexes in patients with frequent
exacerbations (P = .002). Microbiota composition was heterogeneous, but there was
a correlation between NET complexes and both microbiota diversity (P = .009) and
dominance of Haemophilus species operational taxonomic units (P = .01). Ex vivo
airway neutrophil phagocytosis of bacteria was reduced in patients with increased
sputum NET complexes. Consistent results were observed regardless of the method
of quantifying sputum NETs. Failure of phagocytosis could be induced
experimentally by incubating healthy control neutrophils with soluble sputum from
patients with COPD. CONCLUSION: NET formation is increased in patients with
severe COPD and associated with more frequent exacerbations and a loss of
microbiota diversity.
PMID- 28506853
TI - Expression of semaphorin 3E is suppressed in severe asthma.
PMID- 28506854
TI - Long-Term Safety and Efficacy of Solifenacin in Children and Adolescents with
Overactive Bladder.
AB - PURPOSE: We evaluated the long-term safety and efficacy of once daily oral
solifenacin suspension in children (5 to less than 12 years old) and adolescents
(12 to less than 18 years old) with overactive bladder. MATERIALS AND METHODS: We
conducted a 40-week, open label extension of a 12-week double-blind, placebo
controlled trial. Outcome measures included incidence and severity of adverse
events (primary end point), laboratory variables, vital signs, 12-lead
electrocardiogram, post-void residual volume, and change from baseline to end of
treatment in mean number of micturitions and incontinence episodes per 24 hours,
number of incontinence-free days per 7 days and number of grade 3 or 4 urgency
episodes per 24 hours (adolescents only). RESULTS: A total of 119 children and 29
adolescents were enrolled in the study. The incidence of drug related treatment
emergent adverse events was 34.7% (children) and 37.9% (adolescents), the most
common of which were constipation (11.9%), electrocardiogram QT prolonged (8.5%)
and dry mouth (4.2%) in children, and electrocardiogram QT prolonged (13.8%) and
nausea (6.9%) in adolescents. Adverse events resulted in 10.2% (children) and
13.8% (adolescents) of participants discontinuing treatment. There were no cases
of urinary retention or increases in post-void residual volume and no clinically
relevant changes in laboratory variables or vital signs. Two cases of dizziness
but no other central nervous system drug related treatment emergent adverse
events were reported. Improvements in all efficacy parameters and grade 3 or 4
urgency episodes observed by 3 weeks were further improved and/or maintained
during the study. CONCLUSIONS: Once daily solifenacin oral suspension was well
tolerated for up to 52 weeks in children 5 to less than 12 years old and
adolescents 12 to less than 18 years old diagnosed with overactive bladder, with
constipation and electrocardiogram QT prolonged as the most common adverse
reactions, respectively. Improvements in efficacy at 3 weeks were sustained
during the study.
PMID- 28506855
TI - Rates and Risk Factors for Opioid Dependence and Overdose after Urological
Surgery.
AB - PURPOSE: Effective pain management is a critical component of the perioperative
process with opioids representing a mainstay of therapy. The opioid epidemic is a
growing concern in the United States. The goal of this study was to quantify the
risk of opioid dependence or overdose among patients undergoing urological
surgery and to identify risk factors of opioid dependence or overdose. MATERIALS
AND METHODS: We retrospectively reviewed data on urological surgery from 2007 to
2011. Data sources included the HCUP (Healthcare Cost and Utilization Project)
inpatient, ambulatory surgery and emergency department data sets. Outcomes of
postoperative opioid dependence and overdose were identified by previously
validated ICD-9 codes. Multivariable logistic regression adjusted for surgical
procedure was performed to identify predictors of opioid dependence or overdose
following urological surgery. RESULTS: Overall 675,527 patients underwent
urological surgery, of whom 0.09% were diagnosed with opioid dependence or
overdose. Patients in whom opioid dependence or overdose developed were younger
(median age 51 vs 62 years), carried nonprivate insurance (69.6% vs 66%),
underwent an inpatient procedure (81.0% vs 42.4%) and had a longer length of stay
(median 3 vs 0 days) and a history of depression (14.4% vs 3.4%) or chronic
obstructive pulmonary disease (20.3% vs 8.9%, all p <0.001). On adjusted
multivariable analysis these factors remained independent risk factors for opioid
dependence or overdose. CONCLUSIONS: Postoperative opioid dependence or overdose
affects 1 of 1,111 urological surgery patients. Risk factors for opioid
dependence or overdose included younger age, inpatient surgery and increasing
hospitalization duration, baseline depression, tobacco use and chronic
obstructive pulmonary disease as well as insurance provider, including Medicaid,
Medicare (age less than 65 years) and noninsured status.
PMID- 28506856
TI - Bariatric surgery revisions and private health insurance.
AB - OBJECTIVE: To identify: 1. The percentage of bariatric procedures that are
revisions; 2. What proportion of bariatric revision procedures in public
hospitals are for patients whose primary weight loss procedure occurred in a
private hospital; 3. The age, sex and level of socioeconomic disadvantage of
patients needing revisions. METHODS: An analysis of patient level admission data
from the Integrated South Australian Activity Collection (ISAAC) was performed.
Data were collected on all revisions for weight loss related procedures at all
South Australian public and private hospitals, between 2000-2015 using the ISAAC
codes for revision procedures. RESULTS: 12,606 bariatric procedures occurred in
hospitals; ~27% of which represent a revision (n=3366). Of these revisions, ~82%
occurred in a private hospital (n=2771), and ~18% occurred in a public hospital
(n=595). Of the 595 revisions in a public hospital, 51% of patients had their
original bariatric procedure performed in a private hospital. The majority of
patients who had a revision procedure are female (>=82%) with a mean age of ~45.
Individuals from the lowest 2 IRSD quintiles were over-represented for public
hospital revisions and primary bariatric procedures. CONCLUSION: Further
investigation is needed to identify: 1. Why 27% of bariatric procedures are
revisions; 2. Why at least 51% of revisions in public hospitals are on patients
whose original primary bariatric procedure was done in a private hospital; 3. The
impact that revision procedures in public hospitals, particularly for originally
private weight loss procedures, is having on public hospital wait times; 4. The
impact of socioeconomic disadvantage on weight loss procedure outcomes.
PMID- 28506857
TI - FOXK2, regulted by miR-1271-5p, promotes cell growth and indicates unfavorable
prognosis in hepatocellular carcinoma.
AB - The forkhead transcription factor FOXK2 has been implicated in the progression of
human cancers, but its role and clinical significance in hepatocellular carcinoma
(HCC) have not been explored. Here we showed that FOXK2 expression was increased
and associated with tumor size, TNM stage and vascular invasion. High FOXK2
expression was correlated with poor overall and disease-free survival in two
independent cohorts consisting of 864 patients with HCC. The prognostic value of
FOXK2 was validated by stratified survival analyses in subgroups difined by
factors contributing to worse survival. Multivariate Cox regression model
revealed that FOXK2 served as an independent factor for overall survival. The
FOXK2 expression was reversely connected with miR-1271-5p in clinical samples. Re
introduction of miR-1271 decreased FOXK2 at both mRNA and protein levels.
Luciferase assay confirmed that FOXK2 was a direct target of miR-1271 in HCC
cells. Overexpression of FOXK2 enhanced the cell growth and migration, whereas
FOXK2 silence resulted in the opposite phenotypes. Further studies demonstrated
that FOXK2 exerted oncogenic activity via activation of PI3K/AKT signaling
pathway. Collectively, our data suggest FOXK2 as an oncogene and a promising
prognostic biomarker in HCC. Targeting the newly identified miR-1271/FOXK2/AKT
axis may represent a potential strategy for HCC intervention.
PMID- 28506858
TI - Accuracy of 1H magnetic resonance spectroscopy for quantification of 2
hydroxyglutarate using linear combination and J-difference editing at 9.4T.
AB - Non-invasive detection of 2-hydroxyglutarate (2HG) by magnetic resonance
spectroscopy is attractive since it is related to tumor metabolism. Here, we
compare the detection accuracy of 2HG in a controlled phantom setting via widely
used localized spectroscopy sequences quantified by linear combination of
metabolite signals vs. a more complex approach applying a J-difference editing
technique at 9.4T. Different phantoms, comprised out of a concentration series of
2HG and overlapping brain metabolites, were measured with an optimized point
resolved-spectroscopy sequence (PRESS) and an in-house developed J-difference
editing sequence. The acquired spectra were post-processed with LCModel and a
simulated metabolite set (PRESS) or with a quantification formula for J
difference editing. Linear regression analysis demonstrated a high correlation of
real 2HG values with those measured with the PRESS method (adjusted R-squared:
0.700, p<0.001) as well as with those measured with the J-difference editing
method (adjusted R-squared: 0.908, p<0.001). The regression model with the J
difference editing method however had a significantly higher explanatory value
over the regression model with the PRESS method (p<0.0001). Moreover, with J
difference editing 2HG was discernible down to 1mM, whereas with the PRESS method
2HG values were not discernable below 2mM and with higher systematic errors,
particularly in phantoms with high concentrations of N-acetyl-asparate (NAA) and
glutamate (Glu). In summary, quantification of 2HG with linear combination of
metabolite signals shows high systematic errors particularly at low 2HG
concentration and high concentration of confounding metabolites such as NAA and
Glu. In contrast, J-difference editing offers a more accurate quantification even
at low 2HG concentrations, which outweighs the downsides of longer measurement
time and more complex postprocessing.
PMID- 28506859
TI - The Obstructed Bladder: Expression of Collagen, Matrix Metalloproteinases,
Muscarinic Receptors, and Angiogenic and Neurotrophic Factors in Patients With
Benign Prostatic Hyperplasia.
AB - OBJECTIVE: To evaluate the gene expression of collagen, matrix metalloproteinases
(MMPs) and inhibitors, cholinergic muscarinic receptors (CHRMs), and angiogenic
and nerve growth factors (NGFs) in the bladder of patients with bladder outlet
obstruction caused by benign prostatic hyperplasia (BPH). METHODS: We analyzed
bladder specimens from 43 patients with obstructive BPH undergoing transurethral
resection of the prostate as compared to 10 age-matched controls with an
International Prostatic Symptom Score of <8 and a prostate volume of <30 g. A
bladder biopsy was performed for relative gene expression analysis with
quantitative real-time polymerase chain reaction of collagens I and III, MMP-1,
MMP-2, and MMP-9; tissue inhibitors of metalloproteinases (TIMPs) TIMP-1, TIMP-2,
and reversion-inducing cysteine-rich protein with kazal motifs (RECK); CHRM2 and
CHRM3; VEGF and CD105; and NGF and nerve growth factor receptor (NGFr). RESULTS:
Patients with bladder outlet obstruction presented a statistically significant
overexpression of collagens I and III, VEGF, CHRM2, and CHRM3. CD105, MMP-9, and
TIMP-1 were underexpressed. Expressions of NGF, NGFr, MMP-1, MMP-2, TIMP-2, and
RECK were heterogeneous. CHRM2 and CHRM3 were overexpressed in patients with
persistent detrusor overactivity. Smokers presented an upregulation of NGFr and
VEGF; dyslipidemic patients had an overexpression of NGFr. CONCLUSION: Bladder
upregulation of collagens I and III on transcriptional level appears to be
relevant in BPH. Muscarinic receptors CHRM2 and CHRM3 are also overexpressed,
more so in patients with persistent detrusor overactivity. Upregulation of VEGF
and NGFr, particularly in subjects with risk factors for atherosclerosis,
reinforces the role of ischemia in BPH-induced modifications of the bladder.
PMID- 28506860
TI - Characterization of Late Recurrence After Radical Cystectomy in a Large
Multicenter Cohort of Bladder Cancer Patients.
AB - OBJECTIVE: To investigate the characteristics and outcomes of late recurrence
(LR) in patients with bladder cancer (BCa) treated with radical cystectomy (RC)
and to identify clinicopathologic predictors of LR and postrecurrence survival.
MATERIALS AND METHODS: This multicenter study included 1652 BCa patients. LR was
defined as occurring more than 5 years after RC. Differences in postrecurrence
overall survival according to the timing of disease recurrence and the location
of recurrence were calculated using the log-rank test. A logistic regression
model was used to identify predictors of LR, and Cox regression models were used
to evaluate variables associated with postrecurrence overall survival (OS).
RESULTS: Overall, 548 patients experienced disease recurrence. Of these, 67
patients (12.2%) experienced LR, with a median time to recurrence of 86 months
(interquartile range 70.5-107.2). LR was more likely to be located in the
urothelium (P = .005). On multivariable analysis, younger age (P = .008) and non
organ confined disease (P = .03) were found to be predictors of LR.
Postrecurrence 5-year OS was worse in patients who experienced early recurrence
compared with those with LR (12% vs 25%, P = .02) and in those with nonurothelial
recurrence compared to those with disease recurrence in the remaining urothelium
(12% vs 51%, P < .001). Older age (P < .001), non-organ confined disease at RC (P
= .02), and nonurothelial recurrence site (P = .002) were independently
associated with postrecurrence OS. CONCLUSION: LR after RC is an uncommon but non
negligible event that harbors unique characteristics. LR is associated with
better OS compared to early recurrence. Our findings reinforce the need for
lifelong follow-up of BCa patients after RC.
PMID- 28506861
TI - Do Urinary Leakage Circumstances in Women With Urinary Incontinence Correlate
With Physician Diagnosis and Urodynamic Results? A Questionnaire Validation
Study.
AB - OBJECTIVE: To investigate if leakage circumstances collected using the Urinary
Leakage Circumstances Questionnaire (ULCQ) are correlated with physician
diagnosis and urodynamic results and resolve after surgery. MATERIALS AND
METHODS: The ULCQ was developed to investigate leakage circumstances encountered
by women with incontinence. Women completed both the ULCQ and the International
Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form before
clinical and urodynamic examination. Those who underwent a suburethral sling
procedure completed both questionnaires postoperatively. We performed a principal
component analysis and evaluated the questionnaire's external properties
including construct validity and responsiveness. RESULTS: One hundred and eighty
six women were included in the validation phase, and 168 underwent suburethral
sling procedure. Mean postoperative follow-up was 51 months. Principal component
analysis identified 4 dimensions from the 23 leakage circumstances listed in the
ULCQ: effort, stimulation, postural, and intercourse; the internal consistency of
each dimension was excellent (Cronbach alpha: 0.87, 0.86, 0.82, and 0.79,
respectively). Effort (+0.39), stimulation (+0.24), and postural (+0.47)
dimensions were correlated with the International Consultation on Incontinence
Questionnaire-Urinary Incontinence Short Form score; the effort dimension was
correlated with greater stress incontinence severity assessed by the physician;
the stimulation dimension with urgency and urge incontinence severity assessed by
the physician, and with lower volumes during cystometry; and the postural
dimension with higher age and lower urethral closure pressure. Each dimension
recorded a significant improvement after surgery, with the largest effect size
for effort dimension (2.29 [confidence interval 95%: 1.96-2.62]). CONCLUSION: The
ULCQ is a useful tool for investigating female urinary incontinence and detecting
changes after surgery.
PMID- 28506862
TI - A Relevant Midterm (12 Months) Placebo Effect on Lower Urinary Tract Symptoms and
Maximum Flow Rate in Male Lower Urinary Tract Symptom and Benign Prostatic
Hyperplasia-A Meta-analysis.
AB - OBJECTIVE: To assess the mid- to long-term placebo effect of the medical and
instrumental management of male lower urinary tract symptoms. This is generally a
long-term treatment strategy. Therefore, knowledge on the mid- to long-term
placebo effect is of considerable interest. The paucity of data on this topic
prompted us to investigate this issue in a meta-analysis. METHODS: All randomized
controlled trials (RCTs) with the indication of benign prostatic hyperplasia and
lower urinary tract symptoms containing a placebo- or sham treatment arm and with
a follow-up of 12 months were eligible. The 12-month effect of placebo or sham
treatment on the International Prostate Symptom Score (the quality-of-life
question was not analyzed herein) and the American Urological Association Symptom
Score and on the maximum flow rate was quantified. RESULTS: A total of 25 RCTs
with 10.587 patients were eligible. Twenty-three studies were placebo controlled
(plant extracts: n = 4, 5alpha-reductase inhibitors [5ARIs]: n = 9, alpha
blocker: n = 5, combination therapy of 5ARI and alpha-blocker: n = 3, and
intraprostatic botulinum toxin A injection: n = 2), and 2 RCTs with transurethral
microwave thermotherapy (TUMT) had a sham treatment arm. At 12 months, the mean
International Prostate Symptom Score improved by a mean of 4.4 points under
placebo or sham treatment with a range of 0.7-6.8 points: plant extracts, -3.6;
5ARI, -3.4; alpha-blocker, -4.3; combination therapy, -4.3; botulinum toxin A,
3.9; and TUMT, -6.8. The mean maximum flow rate improvement at 12 months under
placebo or sham was not relevant (+0.8 mL/s), yet there were remarkable
differences between trials: plant extracts, -0.3 mL/s; 5ARI, +0.8 mL/s; alpha
blocker, +1.1 mL/s; combination therapy, +1.4 mL/s; and TUMT, +1.0 mL/s.
CONCLUSION: This meta-analysis demonstrates the mid-term placebo effect on lower
urinary tract function, particularly concerning subjective improvement. The
degree of the placebo effect varies considerable between studies even at 12
months.
PMID- 28506863
TI - The Null-Test for peptide identification algorithm in Shotgun proteomics.
AB - : The present research proposed general evaluation strategy named Null-Test for
peptide identification algorithm in Shotgun proteomics. The Null-Test method
based on random matching can be utilized to check whether the algorithm has a
tendency to make a mistake or has potential bugs, faultiness, errors etc., and to
validate the reliability of the identification algorithm. Unfortunately, none of
the five famous identification software could pass the most stringent Null-Test.
PatternLab had good performance in both Null-Test and routine search by making a
good control on the overfitting with sound design. The fuzzy logics based method
presented as another candidate strategy could pass the Null-Test and has
competitive efficiency in peptide identification. Filtering the results by
appropriate FDR would increase the number of discoveries in an experiment, at the
cost of losing control of Type I errors. Thus, it is necessary to utilize some
more stringent criteria when someone wants to design or analyze an
algorithm/software. The more stringent criteria will facilitate the discovery of
latent bugs, faultiness, errors etc. in the algorithm/software. It would be
recommended to utilize independent search combining random database with
statistics theorem to estimate the accurate FDR of the identified results.
BIOLOGICAL SIGNIFICANCE: In the past decades, considerable effort has been
devoted to developing a sensitive algorithm for peptide identification in Shotgun
proteomics. However, little attention has been paid to controlling the
reliability of the identification algorithm at the design stage. The Null-Test
based on random matching can be utilized to check whether the algorithm has a
tendency to make a mistake or has potential bugs, faultiness, errors etc.
However, it turns out that none of the five famous identification software could
pass the most stringent Null-Test in the present study, which should be taken
into account seriously. Accordingly, a candidate strategy based on fuzzy logics
has been demonstrated the possibility that an identification algorithm can pass
the Null-Test. PatternLab shows that earlier control on overfitting is valuable
for designing an efficient algorithm.
PMID- 28506864
TI - Asking the right questions.
PMID- 28506865
TI - Protocol-driven neurological prognostication and withdrawal of life-sustaining
therapy after cardiac arrest and targeted temperature management.
AB - BACKGROUND: Brain injury is reportedly the main cause of death for patients
resuscitated after out-of-hospital cardiac arrest (OHCA). However, the majority
may actually die following withdrawal of life-sustaining therapy (WLST) with a
presumption of poor neurological recovery. We investigated how the protocol for
neurological prognostication was used and how related treatment recommendations
might have affected WLST decision-making and outcome after OHCA in the targeted
temperature management (TTM) trial. METHODS: Analyses of prospectively recorded
data: details of neurological prognostication; recommended level-of-care; WLST
decisions; presumed cause of death; and cerebral performance category (CPC) 6
months following randomization. RESULTS: Of 939 patients, 452 (48%) woke and 139
(15%) died, mostly for non-neurological reasons, before a scheduled time point
for neurological prognostication (72h after the end of TTM). Three hundred and
thirteen (33%) unconscious patients underwent prognostication at a median 117
(IQR 93-137) hours after arrest. Thirty-three (3%) unconscious patients were not
neurologically prognosticated and for 2 patients (1%) data were missing. Related
care recommendations were: continue in 117 (37%); not escalate in 55 (18%); and
withdraw in 141 (45%). WLST eventually occurred in 196 (63%) at median day 6 (IQR
5-8). At 6 months, only 2 patients with WLST were alive and 248 (79%) of
prognosticated patients had died. There were significant differences in time to
WLST and death after the different recommendations (log rank <0.001). CONCLUSION:
Delayed prognostication was relevant for a minority of patients and related to
subsequent decisions on level-of-care with effects on ICU length-of-stay,
survival time and outcome.
PMID- 28506866
TI - Non-maturational covariates for dynamic systems pharmacology models in neonates,
infants, and children: Filling the gaps beyond developmental pharmacology.
AB - Pharmacokinetics and -dynamics show important changes throughout childhood.
Studies on the different maturational processes that influence developmental
pharmacology have been used to create population PK/PD models that can yield
individualized pediatric drug dosages. These models were subsequently translated
to semi-physiologically or physiology-based PK (PBPK) models that support
predictions in pediatric patient cohorts and other special populations. Although
these translational efforts are crucial, these models should be further improved
towards individual patient predictions by including knowledge on non-maturational
covariates. These efforts are needed to ultimately get to systems pharmacology
models for children. These models take developmental changes relating to the
pediatric dynamical system into account but also other aspects that may be of
importance such as abnormal body composition, pharmacogenetics, critical illness
and inflammatory status.
PMID- 28506867
TI - Towards personalized treatment of pain using a quantitative systems pharmacology
approach.
AB - Pain is a complex biopsychosocial phenomenon of which the intensity, location and
duration depends on various underlying components. Treatment of pain is
associated with considerable inter-individual variability, and as such, requires
a personalized approach. However, a priori prediction of optimal analgesic
treatment for individual patients is still challenging. Another challenge is the
assessment and treatment of pain in patients unable to self-report pain. In this
mini-review, we first provide a brief overview of the various components
underlying pain, and their associated biomarkers. These include clinical,
psychosocial, neurophysiological, and biochemical components. We then discuss the
use of empirical and mechanism-based pharmacokinetic-pharmacodynamic modelling to
support personalized treatment of pain. Finally, we propose how these concepts
can be extended to a quantitative systems pharmacology (QSP) approach that
integrates the components of clinical pain and treatment response. This
integrative approach can support predictions of optimal pharmacotherapy of pain,
compared with approaches that focus on single components of pain. Moreover,
combination of QSP modelling with state-of-the-art metabolomics approaches may
offer unique possibilities to identify novel pain biomarkers. Such biomarkers
could support both the personalized treatment of pain and translational drug
development of novel analgesic agents. In conclusion, a QSP approach will likely
improve our ability to predict pain and treatment response, paving the way for
personalized treatment of pain.
PMID- 28506868
TI - Drug-disease modeling in the pharmaceutical industry - where mechanistic systems
pharmacology and statistical pharmacometrics meet.
AB - Modeling & simulation (M&S) methodologies are established quantitative tools,
which have proven to be useful in supporting the research, development (R&D),
regulatory approval, and marketing of novel therapeutics. Applications of M&S
help design efficient studies and interpret their results in context of all
available data and knowledge to enable effective decision-making during the R&D
process. In this mini-review, we focus on two sets of modeling approaches:
population-based models, which are well-established within the pharmaceutical
industry today, and fall under the discipline of clinical pharmacometrics (PMX);
and systems dynamics models, which encompass a range of models of (patho
)physiology amenable to pharmacological intervention, of signaling pathways in
biology, and of substance distribution in the body (today known as
physiologically-based pharmacokinetic models) - which today may be collectively
referred to as quantitative systems pharmacology models (QSP). We next describe
the convergence - or rather selected integration - of PMX and QSP approaches into
'middle-out' drug-disease models, which retain selected mechanistic aspects,
while remaining parsimonious, fit-for-purpose, and able to address variability
and the testing of covariates. We further propose development opportunities for
drug-disease systems models, to increase their utility and applicability
throughout the preclinical and clinical spectrum of pharmaceutical R&D.
PMID- 28506869
TI - Model-based clinical dose optimization for phenobarbital in neonates: An
illustration of the importance of data sharing and external validation.
AB - BACKGROUND: Particularly in the pediatric clinical pharmacology field, data
sharing offers the possibility of making the most of all available data. In this
study, we utilize previously collected therapeutic drug monitoring (TDM) data of
term and preterm newborns to develop a population pharmacokinetic model for
phenobarbital. We externally validate the model using prospective phenobarbital
data from an ongoing pharmacokinetic study in preterm neonates. METHODS: TDM data
from 53 neonates (gestational age (GA): 37 (24-42) weeks, bodyweight: 2.7 (0.45
4.5) kg; postnatal age (PNA): 4.5 (0-22) days) contained information on dosage
histories, concentration and covariate data (including birth weight, actual
weight, post-natal age (PNA), postmenstrual age, GA, sex, liver and kidney
function, APGAR-score). Model development was carried out using NONMEM(r) 7.3.
After assessment of model fit, the model was validated using data of 17 neonates
included in the DINO (Drug dosage Improvement in NeOnates)-study. RESULTS:
Modelling of 229 plasma concentrations, ranging from 3.2 to 75.2mg/L, resulted in
a one compartment model for phenobarbital. Clearance (CL) and volume (Vd) for a
child with a birthweight of 2.6kg at PNA day 4.5 was 0.0091L/h (9%) and 2.38L
(5%), respectively. Birthweight and PNA were the best predictors for CL
maturation, increasing CL by 36.7% per kg birthweight and 5.3% per postnatal day
of living, respectively. The best predictor for the increase in Vd was actual
bodyweight (0.31L/kg). External validation showed that the model can adequately
predict the pharmacokinetics in a prospective study. CONCLUSION: Data-sharing can
help to successfully develop and validate population pharmacokinetic models in
neonates. From the results it seems that both PNA and bodyweight are required to
guide dosing of phenobarbital in term and preterm neonates.
PMID- 28506870
TI - Development of solid SEDDS, VII: Effect of pore size of silica on drug release
from adsorbed self-emulsifying lipid-based formulations.
AB - PURPOSE: Lipid-based self-emulsifying drug delivery systems (SEDDS) are usually
liquids, and they can be converted into solid dosage forms by adsorbing onto
silicates. However, most commercially available silicates are mesoporous with
small pore sizes of 1 to 50nm that lead to incomplete emulsification of SEDDS
inside the pores and thus incomplete drug release. The objective of this study
was to investigate the impact of silica pore size on the extent of drug release
from SEDDS solidified by adsorbing onto macroporous silicas with different pore
sizes. METHODS: Silicas with average pore sizes of approx. 150nm, 500nm and 5MUm
were synthesized using the colloidal crystal templating method. A model poorly
water-soluble drug, probucol, was dissolved in liquid SEDDS containing different
lipid to surfactant ratios, and the formulations were then adsorbed onto equal
weights of silicas (1:1 w/w ratio). Drug release from freshly prepared
formulations and after storing at 40 degrees C/60% RH for up to 6months was
studied using a modified USP type 2 method with mini paddles and 50mL of 0.01M
HCl (pH~2) at 37 degrees C. Drug release was also studied similarly from silicas
that were precoated with PVP K-30 at 5, 10, 20 and 30% w/w levels before
adsorption of SEDDS. RESULTS: Freshly prepared formulations containing relatively
higher lipid:surfactant ratio of 7:3% w/w exhibited 17, 40 and 60% drug release
from uncoated (neat) silicas with pore sizes of 150nm, 500nm and 5MUm,
respectively, while the more hydrophilic formulations containing 3:7 w/w
lipid:surfactant ratio had, respectively, 50, 65 and 85% drug release. No
decrease in drug release was observed when the formulations were exposed to 40
degrees C/60% RH for up to 6months. When the silicas were precoated with 20% PVP,
the drug release was almost complete (>80%), which remained unchanged even after
6months of storage irrespective of the composition of adsorbed liquid SEDDS.
CONCLUSIONS: Both pore size and composition of SEDDS had major impacts on drug
release from silicas. Increased drug release was observed with the increase in
pore size of silicas and hydrophilicity of formulations. Since the silicas
synthesized were macroporous with no mesopores present, there was no decrease in
drug release upon storage. Complete drug release was observed when silicas were
precoated with PVP as it increased the penetration of water into the pores.
PMID- 28506871
TI - The role of hyaluronan as a drug carrier to enhance the bioavailability of
extended release ophthalmic formulations. Hyaluronan-timolol ionic complexes as a
model case.
AB - The aim of this work was to obtain information concerning the properties of
ophthalmic formulations based on hyaluronic-drug ionic complexes, to identify the
factors that determine the onset, intensity and duration of the
pharmacotherapeutic effect. Dispersions of a complex of 0.5% w/v of sodium
hyaluronate (HyNa) loaded with 0.5% w/v of timolol maleate (TM) were obtained and
presented a counterionic condensation higher than 75%. For comparison a similar
complex obtained with hyaluronic acid (HyH) was also prepared. Although the
viscosity of HyNa-TM was significantly higher than that of HyH-TM, in vitro
release of TM from both complexes showed a similar extended drug release profile
(20-31% over 5h) controlled by diffusion and ionic exchange. Ocular
pharmacokinetic study performed in normotensive rabbits showed that HyNa-TM
complex exhibited attractive bioavailability properties in the aqueous humor (AUC
and Cmax significantly higher and later Tmax) compared to commercial TM eye
drops. Moreover, a more prolonged period of lowered intra-ocular pressure (10h)
and a more intense hypotensive activity was observed after instillation of a drop
of HyNa-TM as compared to the eye-drops. Such behavior was related to the longer
pre-corneal residence times (400%) observed with HyNa-TM complex. No significant
changes in rabbit transcorneal permeation were detected upon complexation. These
results demonstrate that the ability of HyNa to modulate TM release, together
with its mucoadhesiveness related to the viscosity, affected both the
pharmacokinetic and pharmacodynamic parameters. The HyNa-TM complex is a
potentially useful carrier for ocular drug delivery, which could improve the TM
efficacy and reduce the frequency of administration to improve patient
compliance.
PMID- 28506872
TI - Unreliability of putative fMRI biomarkers during emotional face processing.
AB - There is considerable need to develop tailored approaches to psychiatric
treatment. Numerous researchers have proposed using functional magnetic resonance
imaging (fMRI) biomarkers to predict therapeutic response, in particular by
measuring task-evoked subgenual anterior cingulate (sgACC) and amygdala
activation in mood and anxiety disorders. Translating this to the clinic relies
on the assumption that blood-oxygen-level dependent (BOLD) responses in these
regions are stable within individuals. To test this assumption, we scanned a
group of 29 volunteers twice (mean test-retest interval=14.3 days) and calculated
the within-subject reliability of the amplitude of the amygdalae and sgACC BOLD
responses to emotional faces using three paradigms: emotion identification;
emotion matching; and gender classification. We also calculated the reliability
of activation in a control region, the right fusiform face area (FFA). All three
tasks elicited robust group activations in the amygdalae and sgACC (which changed
little on average over scanning sessions), but within-subject reliability was
surprisingly low, despite excellent reliability in the control right FFA region.
Our findings demonstrate low statistical reliability of two important putative
treatment biomarkers in mood and anxiety disorders.
PMID- 28506874
TI - Impact of acquisition and analysis strategies on cortical depth-dependent fMRI.
AB - Functional MRI at ultra-high magnetic fields (>= 7T) provides the opportunity to
probe columnar and laminar processing in the human brain in vivo at sub
millimeter spatial scales. However, fMRI data only indirectly reflects the
neuronal laminar profile due to a bias to ascending and pial veins inherent in
gradient- and spin-echo BOLD fMRI. In addition, accurate delineation of the
cortical depths is difficult, due to the relatively large voxel sizes and lack of
sufficient tissue contrast in the functional images. In conventional depth
dependent fMRI studies, anatomical and functional data are acquired with
different image read-out modules, the fMRI data are distortion-corrected and
vascular biases are accounted for by subtracting the depth-dependent activation
profiles of different stimulus conditions. In this study, using high-resolution
gradient-echo fMRI data (0.7 mm isotropic) of the human visual cortex, we propose
instead, that depth-dependent functional information is best preserved if data
analysis is performed in the original functional data space. To achieve this, we
acquired anatomical images with high tissue contrast and similar distortion to
the functional images using multiple inversion-recovery time EPI, thereby
eliminating the need to un-distort the fMRI data. We demonstrate higher spatial
accuracy for the cortical layer definitions of this approach as compared to the
more conventional approach using MP2RAGE anatomy. In addition, we provide
theoretical arguments and empirical evidence that vascular biases can be better
accounted for using division instead of subtraction of the depth-dependent
profiles. Finally, we show that the hemodynamic response of grey matter has
relatively stronger post-stimulus undershoot than the pial vein voxels. In
summary, we show that the choice of fMRI data acquisition and processing can
impact observable differences in the cortical depth profiles and present evidence
that cortical depth-dependent modulation of the BOLD signal can be resolved using
gradient-echo imaging.
PMID- 28506873
TI - Transcranial manganese delivery for neuronal tract tracing using MEMRI.
AB - There has been a growing interest in the use of manganese-enhanced MRI (MEMRI)
for neuronal tract tracing in mammals, especially in rodents. For this MEMRI
application, manganese solutions are usually directly injected into specific
brain regions. Recently it was reported that manganese ions can diffuse through
intact rat skull. Here the local manganese concentrations in the brain tissue
after transcranial manganese application were quantified and the effectiveness of
tracing from the area under the skull where delivery occurred was determined. It
was established that transcranially applied manganese yields brain tissue
enhancement dependent on the location of application on the skull and that
manganese that enters the brain transcranially can trace to deeper brain areas.
PMID- 28506875
TI - Deubiquitinase USP33 is negatively regulated by beta-TrCP through ubiquitin
dependent proteolysis.
AB - Ubiquitin-mediated proteolysis regulates cellular levels of various proteins, and
therefore plays important roles in controlling cell signaling and disease
progression. The Skp1-Cul1-F-box ubiquitin ligase beta-TrCP is recognized as an
important negative regulator for numerous key signaling proteins. Recently, the
deubiquitinases (DUBs) have turned out to be essential to regulate signaling
pathways related to human diseases. However, whether beta-TrCP is able to
regulate the deubiquitinase family members remains largely unexplored. Here, we
found that beta-TrCP downregulated cellular levels of endogenous USP33. We also
revealed that beta-TrCP interacted with USP33 independently of the classic
binding motif for beta-TrCP, and mediated USP33 degradation via the ubiquitin
proteasome pathway. Furthermore, we found that the WD40 motif of beta-TrCP and
201-400 amino acid motif of USP33 are required for the interaction between beta
TrCP and USP33. Consequently, beta-TrCP attenuated USP33-mediated inhibition of
cell proliferation and cell invasion. Taken together, our study clarified that
the E3 ligase beta-TrCP regulates cellular USP33 levels by the ubiquitin
proteasomal proteolysis.
PMID- 28506876
TI - Role of prostacyclin synthase in carcinogenesis.
AB - Prostacyclin (PGI2) synthase (PGIS) and microsomal prostaglandin (PG) E synthase
1 (PGES-1) functionally couple with inducible cyclooxygenase-2 (COX-2) as their
upstream enzymes to produce PGI2 and PGE2, respectively. Non-steroidal anti
inflammatory drugs exert their pharmacological effects including antitumor
effects by the inhibition of COX-2 and thereby suppress this PG biosynthesis.
PGIS is abundantly expressed in vascular endothelial and smooth muscle cells and
was shown to be critical for the regulation of platelet aggregation and vascular
tone. In addition to its role in vascular regulation, PGIS was shown to be
frequently down-regulated in several types of cancers, and the involvement of
PGIS in carcinogenesis has been suggested. In this review, we summarize the
current understanding of the roles of PGIS and PGIS-derived PGI2 in
carcinogenesis.
PMID- 28506877
TI - Clinical Practice Guidelines: Synthesis of the guidelines for the surgical
treatment of primary pelvic organ prolapse in women by the AFU, CNGOF, SIFUD-PP,
SNFCP, and SCGP.
PMID- 28506878
TI - Pain-motor integration in the primary motor cortex in Parkinson's disease.
AB - BACKGROUND: In Parkinson's disease (PD), the influence of chronic pain on motor
features has never been investigated. We have recently designed a technique that
combines nociceptive system activation by laser stimuli and primary motor cortex
(M1) activation through transcranial magnetic stimulation (TMS), in a laser
paired associative stimulation design (Laser-PAS). In controls, Laser-PAS induces
long-term changes in motor evoked potentials reflecting M1 long-term potentiation
like plasticity, arising from pain-motor integration. OBJECTIVE: We here examined
the possible influence of chronic pain on motor responses to Laser-PAS in
patients with PD, with and without chronic pain. METHODS: We compared motor
responses to Laser-PAS in healthy subjects and in patients with PD, with and
without chronic pain. RESULTS: Unlike controls, we found reduced responses to
Laser-PAS in patients with PD, with and without pain. Patients off and on
dopaminergic therapy had similar responses to Laser-PAS. When comparing responses
to Laser-PAS in patients with and without pain, the two patients' subgroups had
similar abnormalities. When we compared patients with pain in the body region
investigated with Laser-PAS, with those with pain in other body regions, we found
prominent changes in patients with homotopic pain. Finally, when comparing Laser
PAS with the original PAS protocol, which combines electric peripheral nerve
stimuli and TMS, in patients without pain and those with homotopic pain, we found
similar responses to both techniques in patients without pain, whereas Laser-PAS
induced greater abnormalities than PAS in patients with pain. CONCLUSIONS: In PD,
chronic pain degrades response to Laser-PAS through abnormal pain-motor
integration.
PMID- 28506879
TI - A new platform for long-term tracking and recording of neural activity and
simultaneous optogenetic control in freely behaving Caenorhabditis elegans.
AB - BACKGROUND: Real-time recording and manipulation of neural activity in freely
behaving animals can greatly advance our understanding of how neural circuits
regulate behavior. Ca2+ imaging and optogenetic manipulation with optical probes
are key technologies for this purpose. However, integrating the two optical
approaches with behavioral analysis has been technically challenging. NEW METHOD:
Here, we developed a new imaging system, ICaST (Integrated platform for Ca2+
imaging, Stimulation, and Tracking), which combines an automatic worm tracking
system and a fast-scanning laser confocal microscope, to image neurons of
interest in freely behaving C. elegans. We optimized different excitation
wavelengths for the concurrent use of channelrhodopsin-2 and G-CaMP, a green
fluorescent protein (GFP)-based, genetically encoded Ca2+ indicator. RESULTS:
Using ICaST in conjunction with an improved G-CaMP7, we successfully achieved
long-term tracking and Ca2+ imaging of the AVA backward command interneurons
while tracking the head of a moving animal. We also performed all-optical
manipulation and simultaneous recording of Ca2+ dynamics from GABAergic motor
neurons in conjunction with behavior monitoring. COMPARISON WITH EXISTING
METHOD(S): Our system differs from conventional systems in that it does not
require fluorescent markers for tracking and can track any part of the worm's
body via bright-field imaging at high magnification. Consequently, this approach
enables the long-term imaging of activity from neurons or nerve processes of
interest with high spatiotemporal resolution. CONCLUSION: Our imaging system is a
powerful tool for studying the neural circuit mechanisms of C. elegans behavior
and has potential for use in other small animals.
PMID- 28506881
TI - Altered circadian patterns of salivary cortisol in individuals with
schizophrenia: A critical literature review.
AB - This article focuses on stress vulnerability in schizophrenia through an
integrated clinical and biological approach. The objective of this article is to
better understand the relationships between vulnerability, stress and
schizophrenia. First, the concept of vulnerability is defined and several models
of vulnerability in schizophrenia are reviewed. Second, a section is developed on
the biology of stress, and more specifically on the stress responses of the
hypothalamo-pitutary adrenal (HPA) axis. Then, studies of cortisol circadian
rhythms are summarized, suggesting hyper-reactivity of the HPA axis in patients
with schizophrenia and high risk individuals for schizophrenia. The results
support the models of stress vulnerability in schizophrenia and the hypothesis of
high cortisol levels as an endophenotype in this disorder. In conclusion, this
article highlights the interest of studying the cortisol circadian rhythms in
schizophrenia and opens the perspective to identify high risk individuals for
schizophrenia by measuring circadian patterns of salivary cortisol.
PMID- 28506880
TI - Advanced correlation grid: Analysis and visualisation of functional connectivity
among multiple spike trains.
AB - BACKGROUND: This study analyses multiple spike trains (MST) data, defines its
functional connectivity and subsequently visualises an accurate diagram of
connections. This is a challenging problem. For example, it is difficult to
distinguish the common input and the direct functional connection of two spike
trains. NEW METHOD: The new method presented in this paper is based on the
traditional pairwise cross-correlation function (CCF) and a new combination of
statistical techniques. First, the CCF is used to create the Advanced Correlation
Grid (ACG) correlation where both the significant peak of the CCF and the
corresponding time delay are used for detailed analysis of connectivity. Second,
these two features of functional connectivity are used to classify connections.
Finally, the visualization technique is used to represent the topology of
functional connections. RESULTS: Examples are presented in the paper to
demonstrate the new Advanced Correlation Grid method and to show how it enables
discrimination between (i) influence from one spike train to another through an
intermediate spike train and (ii) influence from one common spike train to
another pair of analysed spike trains. COMPARISON WITH EXISTING METHODS: The ACG
method enables scientists to automatically distinguish between direct connections
from spurious connections such as common source connection and indirect
connection whereas existing methods require in-depth analysis to identify such
connections. CONCLUSIONS: The ACG is a new and effective method for studying
functional connectivity of multiple spike trains. This method can identify
accurately all the direct connections and can distinguish common source and
indirect connections automatically.
PMID- 28506882
TI - Examination of the superoxide/hydrogen peroxide forming and quenching potential
of mouse liver mitochondria.
AB - Pyruvate dehydrogenase (PDHC) and alpha-ketoglutarate dehydrogenase complex
(KGDHC) are important sources of reactive oxygen species (ROS). In addition, it
has been found that mitochondria can also serve as sinks for cellular hydrogen
peroxide (H2O2). However, the ROS forming and quenching capacity of liver
mitochondria has never been thoroughly examined. Here, we show that mouse liver
mitochondria use catalase, glutathione (GSH), and peroxiredoxin (PRX) systems to
quench ROS. Incubation of mitochondria with catalase inhibitor 3-amino-1,2,4
triazole (triazole) induced a significant increase in pyruvate or alpha
ketoglutarate driven O2-/H2O2 formation. 1-Choro-2,4-dinitrobenzene (CDNB), which
depletes glutathione (GSH), elicited a similar effect. Auranofin (AF), a
thioredoxin reductase-2 (TR2) inhibitor which disables the PRX system, did not
significantly change O2-/H2O2 formation. By contrast catalase, GSH, and PRX were
all required to scavenging extramitochondrial H2O2. In this study, the ROS
forming potential of PDHC, KGDHC, Complex I, and Complex III was also profiled.
Titration of mitochondria with 3-methyl-2-oxovaleric acid (KMV), a specific
inhibitor for O2-/H2O2 production by KGDHC, induced a ~86% and ~84% decrease in
ROS production during alpha-ketoglutarate and pyruvate oxidation. Titration of
myxothiazol, a Complex III inhibitor, decreased O2-/H2O2 formation by ~45%.
Rotenone also lowered ROS production in mitochondria metabolizing pyruvate or
alpha-ketoglutarate indicating that Complex I does not contribute to ROS
production during forward electron transfer from NADH. Taken together, our
results indicate that KGDHC and Complex III are high capacity sites for O2-/H2O2
production in mouse liver mitochondria. We also confirm that catalase plays a
role in quenching either exogenous or intramitochondrial H2O2.
PMID- 28506883
TI - Effects of cardiotonic steroids on isolated perfused kidney and NHE3 activity in
renal proximal tubules.
AB - Cardiotonic steroids (CS) are known as modulators of sodium and water
homeostasis. These compounds contribute to the excretion of sodium under overload
conditions due to its natriuretic property related to the inhibition of the renal
Na+/K+-ATPase (NKA) pump alpha1 isoform. NHE3, the main route for Na+
reabsorption in the proximal tubule, depends on the Na+ gradient generated by the
NKA pump. In the present study we aimed to investigate the effects of
marinobufagin (MBG) and telocinobufagin (TBG) on the renal function of isolated
perfused rat kidney and on the inhibition of NKA activity. Furthermore, we
investigated the mechanisms for the cardiotonic steroid-mediated natriuretic
effect, by evaluating and comparing the effects of bufalin (BUF), ouabain (OUA),
MBG and TBG on NHE3 activity in the renal proximal tubule in vivo. TBG
significantly increased GFR, UF, natriuresis and kaliuresis in isolated perfused
rat kidney, and inhibits the activity of NKA at a much higher rate than MBG. By
stationary microperfusion technique, the perfusion with BUF, OUA, TBG or MBG
promoted an inhibitory effect on NHE3 activity, whereas BUF was the most
effective agent, and demonstrated a dose-dependent response, with maximal
inhibition at 50nM. Furthermore, our data showed the role of NKA-Src kinase
pathway in the inhibition of NHE3 by CS. Finally, a downstream step, MEK1/2
ERK1/2 was also investigated, and, similar to Src inhibition, the MEK1/2
inhibitor (U0126) suppressed the BUF effect. Our findings indicate the
involvement of NKA-SRc-Kinase-Ras-Raf-ERK1/2 pathway in the downregulation of
NHE3 by cardiotonic steroids in the renal proximal tubule, promoting a reduction
of proximal sodium reabsorption and natriuresis.
PMID- 28506884
TI - Enhancing effect of 50 Hz rotating magnetic field on induction of Shiga toxin
converting lambdoid prophages.
AB - Studies aimed at investigating factors and mechanism of induction of prophages, a
major pathogenesis factor of Shiga toxin-producing Escherichia coli (STEC), are
considered important to develop an effective treatment for STEC infections. In
this study, we demonstrated the synergistic effect of the rotating magnetic field
(RMF) of induction B = 34 mT and frequency f = 50 Hz at a constant temperature of
37 degrees C and mitomycin C (MMC), that resulted in a higher level of induction
of stx-carrying lambdoid Stx prophages. This is a first report on the induction
of lambdoid Stx prophages in response to the enhancing effect of popular inductor
(mitomycin C) under the influence of RMF.
PMID- 28506885
TI - High proportions of Staphylococcus epidermidis in dental caries harbor multiple
classes of antibiotics resistance, significantly increase inflammatory
interleukins in dental pulps.
AB - Staphylococcus epidermidis is one of most prevalent in dental caries or dental
pulp which has the capability of horizontal genetic transfer between different
bacterial species in the oropharynx, suggesting that it may evolve with the
dissemination of resistant determinants, This study was performed to molecularly
characterize and differentiate S. epidermidis isolated from dental caries and
healthy individual. Also, two important cytokines in inflammation were assayed
caused due to S. epidermidis of health and dental caries sources. Dental caries
strains were more resistant with high MIC 50 and MIC 90 value. These isolates
also showed the presence of mecA gene and another virulence gene i. e sea and seb
comparatively more than healthy individual isolates. SCCmec types, III and IV was
more prevalent in dental caries isolates where an as healthy individual was more
non-typable. Additionally, the quantity of IL-1beta and IL-8 caused due to dental
caries isolates was seen more which indicate dental caries isolates are able to
induce. This study showed that S. epidermidis a normal flora of oropharyngeal are
more diverse to those strains which cause dental caries. S. epidermidis owns a
prodigious genetic plasticity that permits to obtain, lose or regulate genetic
elements that provide compensations to improve its colonization in the host.
PMID- 28506887
TI - Molecular investigation of virulence factors of Brucella melitensis and Brucella
abortus strains isolated from clinical and non-clinical samples.
AB - Brucella is zoonotic pathogen that induces abortion and sterility in domestic
mammals and chronic infections in humans called Malta fever. It is a facultative
intracellular potential pathogen with high infectivity. The virulence of Brucella
is dependent upon its potential virulence factors such as enzymes and cell
envelope associated virulence genes. The aim of this study was to investigate the
Brucella virulence factors among strains isolated from humans and animals in
different parts of Iran. Seventy eight strains of Brucella species isolated from
suspected human and animal cases from several provinces of Iran during 2015-2016
and identified by phenotypic and molecular methods. The multiplex-PCR (M-PCR)
assay was performed in order to detect the ure, wbkA, omp19, mviN, manA and perA
genes by using gene specific primers. Out of 78 isolates of Brucella spp., 57
(73%) and 21 (27%) isolates were detected as B. melitensis and B. abortus,
respectively, by molecular method. The relative frequency of virulence genes ure,
wbkA, omp19, mviN, manA and perA were 74.4%, 89.7%, 93.6%, 94.9%, 100% and 92.3%,
respectively. Our results indicate that the most of Brucella strains isolated
from this region possess high percent of virulence factor genes (ure, wbkA,
omp19, mviN, manA and perA) in their genome. So, each step of infection can be
mediated by a number of virulence factors and each strain may have a unique
combination of these factors that affected the rate of bacterial pathogenesis.
PMID- 28506886
TI - Experimental mouse lethality of Escherichia coli strains isolated from free
ranging Tibetan yaks.
AB - The present study has examined the virulence potential of Escherichia coli
isolates harboring at least one virulence gene (associated with ExPEC or InPEC
pathotype and belonging to different phylogenetic groups: A, B1, B2 or D),
isolated from free ranging Tibetan yak feces. The E. coli isolates (n = 87) were
characterized for different serogroups and a mouse model of subcutaneous
infection was used to envisage the virulence within these E. coli strains. Of the
87 E. coli isolates examined, 23% of the E. coli isolates caused lethal
infections in a mouse model of subcutaneous infection and were classified as
killer. Moreover, the majority of the killer strains belonged to phylogroup A
(65%) and serogroup O60 or O101 (35%). Phylogroup B1, serogroups O60 and O101
were statistically associated with the killer status (P < 0.05). However,
positive associations (OR >1) were observed between the killer status isolates
and all other bacterial virulence traits. This study comprises the first report
on the virulence potential of E. coli strains isolated from free-ranging Tibetan
yaks feces. Our findings suggest that pathogenic E. coli of free ranging yaks is
highly worrisome, as these feces are used as manures by farmers and therewith
pose a health risk to humans upon exposure.
PMID- 28506888
TI - Calcium-sensing receptor-ERK signaling promotes odontoblastic differentiation of
human dental pulp cells.
AB - Activation of the G protein-coupled calcium-sensing receptor (CaSR) has crucial
roles in skeletal development and bone turnover. Our recent study has identified
a role for activated CaSR in the osteogenic differentiation of human periodontal
ligament stem cells. Furthermore, odontoblasts residing inside the tooth pulp
chamber play a central role in dentin formation. However, it remains unclear how
CaSR activation affects the odontoblastic differentiation of human dental pulp
cells (HDPCs). We have investigated the odontoblastic differentiation of HDPCs
exposed to elevated levels of extracellular calcium (Ca) and strontium (Sr), and
the contribution of CaSR and the L-type voltage-dependent calcium channel (L
VDCC) to this process. Immunochemical staining of rat dental pulp tissue
demonstrated that CaSR was expressed at high levels in the odontoblastic layer,
moderate levels in the sublayer, and low levels in the central pulp tissue.
Although normal HDPCs expressed low levels of CaSR, stimulation with Ca or Sr
promoted both CaSR expression and odontoblastic differentiation of HDPCs along
with increased expression of odontoblastic makers. These effects were inhibited
by treatment with a CaSR antagonist, whereas treatment with an L-VDCC inhibitor
had no effect. Additionally, knockdown of CaSR with siRNA suppressed
odontoblastic differentiation of Ca- and Sr-treated HDPCs. ERK1/2 phosphorylation
was observed in Ca- and Sr-treated HDPCs, whereas CaSR antagonist treatment or
CaSR knockdown blocked ERK1/2 phosphorylation. Furthermore, inhibition of ERK1/2
suppressed mineralization of Ca- and Sr-treated HDPCs. These results suggest that
elevated concentrations of extracellular Ca and Sr induce odontoblastic
differentiation of HDPCs through CaSR activation and the ERK1/2 phosphorylation.
PMID- 28506890
TI - Biomechanics of the transport barrier in the nuclear pore complex.
AB - The nuclear pore complex (NPC) is the selective gateway through which all
molecules must pass when entering or exiting the nucleus. It is a cog in the gene
expression pathway, an entrance to the nucleus exploited by viruses, and a highly
tuned nanoscale filter. The NPC is a large proteinaceous assembly with a central
lumen occluded by natively disordered proteins, known as FG-nucleoporins (or FG
nups). These FG-nups, along with a family of soluble proteins known as nuclear
transport receptors (NTRs), form the selective transport barrier. Although much
is known about the transport cycle and the necessity of NTRs for chaperoning
cargo molecules through the NPC, the mechanism by which NTRs and NTR*cargo
complexes translocate the selective transport barrier is not well understood. How
can disordered FG-nups and soluble NTRs form a transport barrier that is
selective, ATP-free, and fast? In this work, we review various mechanical
approaches - both experimental and theoretical/computational - employed to better
understand the morphology of the FG-nups, and their role in nucleocytoplasmic
transport. Recent experiments on FG-nups tethered to planar surfaces, coupled
with quantitative modelling work suggests that FG-nup morphologies are the result
of a finely balanced system with significant contributions from FG-nup
cohesiveness and entropic repulsion, and from NTR*FG-nup binding avidity; whilst
AFM experiments on intact NPCs suggest that the FG-nups are sufficiently cohesive
to form condensates in the centre of the NPC lumen, which may transiently
dissolve to facilitate the transport of larger cargoes.
PMID- 28506889
TI - NFAM1 signaling enhances osteoclast formation and bone resorption activity in
Paget's disease of bone.
AB - Paget's disease of bone (PDB) is marked by the focal activity of abnormal
osteoclasts (OCLs) with excess bone resorption. We previously detected measles
virus nucleocapsid protein (MVNP) transcripts in OCLs from patients with PDB.
Also, MVNP stimulates pagetic OCL formation in vitro and in vivo. However, the
mechanism by which MVNP induces excess OCLs/bone resorption activity in PDB is
unclear. Microarray analysis identified MVNP induction of NFAM1 (NFAT activating
protein with ITAM motif 1) expression. Therefore, we hypothesize that MVNP
induction of NFAM1 enhances OCL differentiation and bone resorption in PDB. MVNP
transduced normal human PBMC showed an increased NFAM1 mRNA expression without
RANKL treatment. Further, bone marrow cells from patients with PDB demonstrated
elevated levels of NFAM1 mRNA expression. Interestingly, shRNA suppression of
NFAM1 inhibits MVNP induced OCL differentiation and bone resorption activity in
mouse bone marrow cultures. Live cell widefield fluorescence microscopy analysis
revealed that MVNP induced intracellular Ca2+ oscillations and levels were
significantly reduced in NFAM1 suppressed preosteoclasts. Further, western blot
analysis demonstrates that shRNA against NFAM1 inhibits MVNP stimulated PLCgamma,
calcineurin, and Syk activation in preosteoclast cells. Furthermore, NFAM1
expression controls NFATc1, a critical transcription factor expression and
nuclear translocation in MVNP transuded preosteoclast cells. Thus, our results
suggest that MVNP modulation of the NFAM1 signaling axis plays an essential role
in pagetic OCL formation and bone resorption activity.
PMID- 28506891
TI - Viral mechanisms for docking and delivering at nuclear pore complexes.
AB - Some viruses possess the remarkable ability to transport their genomes across
nuclear pore complexes (NPCs) for replication inside the host cell's intact
nuclear compartment. Viral mechanisms for crossing the restrictive NPC passageway
are highly complex and astonishingly diverse, requiring in each case stepwise
interaction between incoming virus particles and components of the nuclear
transport machinery. Exactly how a large viral genome loaded with accessory
proteins is able to pass through the relatively narrow central channel of the NPC
without causing catastrophic structural damage is not yet fully understood. It
appears likely, however, that the overall structure of the NPC changes in
response to the cargo. Translocation may result in nucleic acids being
misdelivered to the cytoplasm. Here we consider in detail the diverse strategies
that viruses have evolved to target and subvert NPCs during infection. For
decades, this process has both captivated and confounded researchers in the
fields of virology, cell biology, and structural biology.
PMID- 28506893
TI - MACPF/CDC proteins in development: Insights from Drosophila torso-like.
AB - The Membrane Attack Complex Perforin-like/Cholesterol-Dependent Cytolysin (MACPF)
superfamily is an ancient and biologically diverse group of proteins that are
best known for pore-forming roles in mammalian immunity and bacterial
pathogenesis. Intriguingly, however, some eukaryotic proteins which contain the
MACPF domain that defines this family do not act in attack or defence, and
instead have distinct developmental functions. It remains unclear whether these
proteins function via pore formation or have a different mechanism of action. Of
these, by far the best characterised is Torso-like (Tsl), the only MACPF member
that has been identified in the fruit fly, Drosophila melanogaster. While it has
long been known to have a role in embryonic patterning, recent studies have shown
that Tsl in fact has multiple roles in development. As such, it presents an
excellent opportunity to investigate how the MACPF domain functions in a
developmental context. Here, we review what is known about Tsl in Drosophila and
other insects, and discuss the potential molecular mechanism by which Tsl and
thus other developmental MACPF proteins may function.
PMID- 28506894
TI - The functional versatility of the nuclear pore complex proteins.
AB - Over the past few decades, it is increasingly evident that nucleoporins are multi
functional proteins that are not only pivotal for the formation of the nuclear
pore complex. They also have key roles in mitosis, gene expression, development
and disease. In this review, the versatility and functions of nucleoporins
outside the NPC will be discussed.
PMID- 28506895
TI - The Node and beyond-using social media in cell and developmental biology.
AB - Traditionally, strong scientific communities have been at least partly built
around physical proximity - either by members of the same department or
institute, or through regular meetings and conferences. The online environment
and the rise of social media platforms now make it easier to build virtual
communities of geographically dispersed people with a common interest. In this
article, we explore how such networks can be nurtured, focussing on the Node - a
community blog for and by developmental biologists. We also discuss the value of
social media outlets like Twitter in building and maintaining scientific
communities online.
PMID- 28506892
TI - The roles of the nuclear pore complex in cellular dysfunction, aging and disease.
AB - The study of the Nuclear Pore Complex (NPC), the proteins that compose it
(nucleoporins), and the nucleocytoplasmic transport that it controls have
revealed an unexpected layer to pathogenic disease onset and progression. Recent
advances in the study of the regulation of NPC composition and function suggest
that the precise control of this structure is necessary to prevent diseases from
arising or progressing. Here we discuss the role of nucleoporins in a diverse set
of diseases, many of which directly or indirectly increase in occurrence and
severity as we age, and often shorten the human lifespan. NPC biology has been
shown to play a direct role in these diseases and therefore in the process of
healthy aging.
PMID- 28506896
TI - Neurodevelopmental MACPFs: The vertebrate astrotactins and BRINPs.
AB - Astrotactins (ASTNs) and Bone morphogenetic protein/retinoic acid inducible
neural-specific proteins (BRINPs) are two groups of Membrane Attack
Complex/Perforin (MACPF) superfamily proteins that show overlapping expression in
the developing and mature vertebrate nervous system. ASTN(1-2) and BRINP(1-3)
genes are found at conserved loci in humans that have been implicated in
neurodevelopmental disorders (NDDs). Here we review the tissue distribution and
cellular localization of these proteins, and discuss recent studies that provide
insight into their structure and interactions. We highlight the genetic
relationships and co-expression of Brinps and Astns; and review recent knock-out
mouse phenotypes that indicate a possible overlap in protein function between
ASTNs and BRINPs.
PMID- 28506897
TI - Aegerolysins: Lipid-binding proteins with versatile functions.
AB - Proteins of the aegerolysin family span many kingdoms of life. They are
relatively widely distributed in bacteria and fungi, but also appear in plants,
protozoa and insects. Despite being produced in abundance in cells at specific
developmental stages and present in secretomes, only a few aegerolysins have been
studied in detail. In particular, their organism-specific physiological roles are
intriguing. Here, we review published findings to date on the distribution,
molecular interactions and biological activities of this family of structurally
and functionally versatile proteins, the aegerolysins.
PMID- 28506898
TI - Chromane isolated from leaves of Dillenia indica improves the neuronal
dysfunction in STZ-induced diabetic neuropathy.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: According to the Indian traditional medicine,
Dillenia indica L. has shown therapeutic efficacy in various diseases. Fruits and
leaves of the plant possess anti-oxidant and anti-inflammatory properties.
Reactive oxygen species, formation of advanced glycation end products (AGEs) and
apoptosis are implicated in the pathogenesis of diabetic neuropathy. AIM OF THE
STUDY: The aim of the present study was to explore the effect of D. indica and
its isolate, chromane (CR), on thermal and mechanical hyperalgesia, allodynia,
MNCV and oxidative-nitrosative stress in streptozotocin-induced experimental
diabetes. MATERIAL AND METHODS: Diabetes was induced by intraperitoneal
administration of Streptozotocin (STZ; 65mg/kg) for the development of diabetic
neuropathy. Chronic treatment with DAE (100, 200 and 400mg/kg, p.o.) and CR (5
and 10mg/kg, p.o.) for 30 days was started from the 60th day of STZ
administration. Development of neuropathy was evident from a marked hyperalgesia
and allodynia; reduced MNCV associated with increased formation of AGEs and
reactive oxygen species. RESULTS: significantly attenuated behavioral and
biochemical changes associated with diabetic neuropathy. Present study suggested
that DAE and CR ameliorated hyperglycemia and diabetic neuropathic pain via
modulation of oxidative-nitrosative stress and reduction in AGEs formation in the
diabetic rats. CONCLUSION: Thus D. indica might be beneficial in chronic
diabetics, ameliorate the progression of diabetic neuropathy and may also find
application in diabetic neuropathic pain.
PMID- 28506899
TI - Hepatoprotective activities of Antrodia camphorata and its triterpenoid compounds
against CCl4-induced liver injury in mice.
AB - ETHNOPHARMACOLOGY RELEVANCE: Antrodia camphorata (AC) is a rare and precious
fungus indigenous to Taiwan used as a traditional medicine for the treatment of
liver injury. Triterpenoids are the major bioactive constituents of A. camphorata
and have been reported to possess hepatoprotective activities. To meet the
increasing demand, artificial cultivation techniques have been developed. AIM OF
THE STUDY: This study aims to evaluate the hepatoprotective activities of AC
samples derived from different cultivation techniques and to dissect the main
active triterpenoid compounds. MATERIALS AND METHODS: The ethanol extracts of
five batches of AC samples, including wild growing fruiting bodies, cutting wood
culture fruiting bodies, dish cultures, cutting wood culture mycelia, and
submerged fermentation mycelia were orally administered (50mg/kg or 200mg/kg) to
ICR mice for 7 days. On the last day, CCl4 (0.2%, 7mL/kg, i.p.) was used to
induce liver injury, and the activities of serum alanine aminotransferase (ALT)
and aspartate aminotransferase (AST) were determined 24h after the injection.
Moreover, a HepG2 cell model treated with CCl4 (0.35%) was used to screen the
protective activities of 29 AC triterpenoids. After incubation for 6h,
viabilities of the cells were tested using MTS assay. The in vivo
hepatoprotective activities of antcin B and antcin K were further studied on the
mice model by ALT and AST tests and histopathologic examinations. To elucidate
the mechanisms, the mRNA levels of iNOS, COX2, TNF-alpha and IL-1beta, and the
protein levels of NF-kappaB (p65/p-p65), iNOS and COX2 in liver tissues were
determined. RESULTS: The wild growing or cutting wood culture fruiting bodies,
and the dish cultures of AC showed more potent activities than the mycelia
(P<0.001). At 20MUM, 16 of 29 triterpenoids showed significant protective
activities, increasing HepG2 cell viability from 46% of the CCl4 group to >90%.
Antcin B and antcin K could dose-dependently (10 or 50mg/kg, 7 days, i.g.)
decrease the serum levels of ALT and AST, and decrease the incidence of liver
necrosis. The effects of 50mg/kg of antcin K or antcin B were almost identical to
those of 100mg/kg silymarin. Furthermore, qRT-PCR and Western blotting analyses
revealed they could down-regulate IL-1beta, TNF-alpha, iNOS, COX-2 and NF-kappaB
in liver tissues at both transcriptional and translational levels. CONCLUSION:
The results indicate that cultivation techniques remarkably affect the
hepatoprotective activities of AC. Antcin K and antcin B are the major
hepatoprotective compounds of A. camphorata, and the mechanism is related with
anti-inflammation. Given its high natural abundance and good oral absorption,
antcin K could be a promising drug candidate for liver injury.
PMID- 28506900
TI - Chinese materia medica used in medicinal diets.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal diets have a history of more than 2000
years. Locally referred to as yaoshan (Chinese: ), a medicinal diet is understood
in China as a dietary product that combines herbs and food with the purpose of
preventing and treating diseases or improving health under the guidance of
traditional Chinese medicine theory. Medicinal diets are used in Chinese people's
daily life and in specialized restaurants. Hundreds of Chinese materia medica
(CMM) are used in medicinal diets; however, a comprehensive evaluation of
medicinal diets is lacking. AIMS OF THE STUDY: This is an exploratory study that
aims to identify the CMM that are most frequently used in medicinal diets and to
provide an updated view of the current situation of medicinal diets in China.
MATERIALS AND METHODS: A field study of 1221 people in 32 Chinese provinces was
conducted over a period of approximately 6 months and included various types of
interviews as well as a written questionnaire. Two approaches were used to
analyse the data collected in the survey: (1) estimating the frequency of CMM
consumed in daily diets; and (2) collecting CMM used in medicinal diet
restaurants. Complementary information on the selected CMM was obtained from
relevant databases, including PubMed, Google Scholar, Baidu Scholar, CNKI, and
Web of Science. RESULTS: Ten CMM were reported as commonly used by more than 50%
of the participants. Among these 10 species, most medicinally used parts were
seeds and fruits. Pharmacological data from the literature revealed that these
species are associated with a wide spectrum of biological properties, including
antitumour (80%), antioxidant (50%), anti-diabetic (40%), antilipemic (40%), anti
aging (40%), antimicrobial (40%) and cardioprotective (40%) activities. Our
survey shows that most medicinal diet restaurants are located in the eastern part
of China, with the greatest numbers being found in Beijing and Guangzhou. Only
Dioscoreae Rhizoma, Lycii Fructus, Chrysanthemi Flos and Longan Arillus were
frequently consumed both in daily diets and at medicinal diet restaurants. Some
of the similarities shared by these 4 species include an extensive history of use
(>2000 years); a sweet flavour; and antioxidant, antidiabetic, antilipemic and
cardioprotective effects. CONCLUSIONS: The 10 most commonly consumed CMM possess
various biological effects that are currently target the most frequent health
problems for the majority of the population. The development of medicinal diet
restaurants has certain regional restrictions and is associated with the local
climate environment and dietary culture. The data revealed by this study provided
useful information for commercial exploitation of medicinal diets and their
components and serve as a basis for further studies on various aspects of
medicinal diets.
PMID- 28506901
TI - New Isoflavonoids from the extract of Rhynchosia precatoria (Humb. & Bonpl. ex
Willd.) DC. and their antimycobacterial activity.
AB - ETHNOPHARMACOLOGY RELEVANCE: The evaluation of the antimycobacterial activity of
extracts of medicinal plants used by Mayos against tuberculosis and respiratory
problems, allowed the identification of Rhynchosia precatoria (Humb. & Bonpl. ex
Willd.) DC (Fabaceae) as the best candidate to find new antimycobacterial
compounds. AIM OF THE STUDY: To isolate and characterize the compounds of R.
precatoria responsible for the inhibitory and bactericidal activity against
Mycobacterium tuberculosis H37Rv and Mycobacterium smegmatis ATCC 700084. To
determine antimycobacterial synergistic effect of pure compounds and their
selectivity index towards Vero cells. MATERIALS AND METHODS: A total of six
flavonoids were purified by silica gel column chromatography. Structural
elucidation of the isolated compounds was achieved by using 1D and 2D NMR
spectroscopy techniques. The configuration at the C-3 chiral center was
established by quantum mechanical calculation of the electronic circular
dichroism (ECD) spectrum. In vitro inhibitory and bactericidal activity against
M. tuberculosis and M. smegmatis were determined with the redox indicator Alamar
Blue (resazurin). Synergy was determined by X/Y quotient. Cytotoxicity was
measured by MTT assay. RESULTS: The isolated compounds were identified as
precatorin A (1), precatorin B (2), precatorin C (3), lupinifolin (4), cajanone
(5) and lupinifolinol (6). Compounds 1-3 are new. Compounds 1 to 5 inhibited the
growth of M. tuberculosis (MIC >=31.25ug/mL); compounds 1, 2, 4 and 5 killed the
bacteria (MBC >=31.25ug/mL) and also inhibited M. smegmatis (MIC >=125ug/mL),
while 1 and 4 also resulted bactericidal (MBC >=125ug/mL). Compounds 4 and 5
presented synergistic effect (X/Y quotient value <0.5) at a concentration of 1/2
MIC of each compound in the combination. Cytotoxicity in murine macrophages (RAW
264.7 cells) gave IC50 values of 13.3-46.98uM, for compounds 1-5. CONCLUSIONS: In
this work we isolated two new isoflavanones (1 and 2), and one new isoflavone (3)
with a weak antimycobacterial activity. The (3R) absolute configuration was
assigned to 1 by computational analysis of its ECD spectrum and to 2 and 5 by
similarity of their ECD spectra with that of 1. We are also reporting by first
time, activity against virulent strain of M. tuberculosis for compounds 4 and 5
and their antimycobacterial synergistic effect.
PMID- 28506902
TI - SKI3301, a purified herbal extract from Sophora tonkinensis, inhibited airway
inflammation and bronchospasm in allergic asthma animal models in vivo.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Sophora tonkinensis (Leguminosae, ST) is a
traditional herbal plant in Korea and China. Its roots and rhizomes have been
used to dissipate heat, to clear toxic material and to treat acute
pharyngolaryngeal infections and sore throats. AIM OF STUDY: In this study, we
tried to investigate the anti-inflammatory and anti-asthmatic effects of a
purified extract (SKI3301) from Sophora tonkinensis using in vitro enzyme assay
models and ovalbumin (OVA)-induced asthma animal models. MATERIALS AND METHODS:
The effect of SKI3301 on pro-inflammatory enzymes such as 5-lipoxygenase,
phosphodiesterase 3 & 4, and thromboxane synthase was assayed in vitro. BALB/c
mice were sensitized with OVA/Alum ip injection and nebulized with OVA to induce
airway inflammation. Bronchoalveolar lavage (BAL) fluid was collected and
analyzed for leukocytes infiltration and IL-5 production along with lung
histopathology. Guinea pigs passively sensitized with anti-OVA antiserum were
used to investigate the effect of SKI3301 on bronchospasm in vitro and in vivo.
RESULTS: SKI3301 potently inhibited the activities of 5-lipoxygenase,
phosphodiesterase 3 & 4, and thromboxane synthase. Orally administered SKI3301
attenuated the total leukocytes and eosinophil infiltration and IL-5 level in BAL
fluids. Histopathological changes associated with lung inflammation were also
reduced by SKI3301. SKI3301 inhibited OVA-induced contraction of isolated trachea
from sensitized guinea pigs. SKI3301 also protected OVA-induced
bronchoconstriction in the sensitized guinea pigs. Maackiain, one of 3 major
components of SKI3301, was effective in inhibiting 5-lipoxygenase and OVA-induced
airway inflammation. CONCLUSION: In this study, SKI3301 potently inhibited pro
inflammatory enzymes and attenuated OVA-induced bronchospasm in animal model of
allergic asthma. These results suggest that SKI3301 may have therapeutic
potential for allergic asthma.
PMID- 28506903
TI - Ethnozoological assessment of animals used by Mon traditional medicine vendors at
Kyaiktiyo, Myanmar.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Wild animals are widely used in traditional Asian
medicine but information from Myanmar is lacking. We show that a wide range of
animals are used at a pilgrimage site, mostly for their rendered fats and oils to
be used in mixed concoctions. The majority of species were sold to be used to
treat aching joints, muscle ache and skin diseases. AIM OF THE STUDY: To assess
wildlife for sale for medicinal purposes, and document their medicinal use at
Kyaiktiyo, a pilgrimage site at a 1100m tall mountain, with many of the pilgrims
climbing to the top. In addition we address legal issues relating to the
production and sale of traditional medicine that contain legally protected
animals. MATERIAL AND METHODS: Four visits were made to Kyaiktiyo, Myanmar,
between 2000 and 2017 to quantify animal parts on display and through discussions
with vendors to obtain information on medicinal use of these parts. RESULTS:
Twenty-three species, mostly mammals, were recorded to be used for traditional
medicine. The most common were Chinese serow Capricornis milneedwardsii, Asian
elephant Elephas maximus, and Asiatic black bear Ursus thibetanus. Over 600
bodies or body parts were present. Combined, these parts purportedly provided
cures or relief for at least 15 ailments or diseases. The most commonly mentioned
treatment was that of using rendered animal fats/oils externally to relieve/cure
aching joints or muscles. This treatment allegedly provides instant relief to
pilgrims after an arduous climb up the mountain. Purported cures for various skin
diseases was the next common use for the animal species on offer. Ten of the
species observed for sale at Kyaiktiyo are listed as globally threatened, and 15
are protected and cannot be legally traded. Ambiguities in Myanmar's legislation
mean that protected animals or their body parts cannot be traded, however
traditional medicines can be made out of them provided rules relating to the
manufacturing of traditional medicines are adhered to. CONCLUSION: This study
indicated that animals and their parts continue to be openly offered for sale at
Kyaiktiyo to treat various illnesses. Despite these products potential medical,
traditional or cultural importance, solutions have to been found on how to ensure
that, in line with Myanmar's laws, use of traditional local medicine does not
impede the conservation of imperilled species.
PMID- 28506904
TI - Ordinal convolutional neural networks for predicting RDoC positive valence
psychiatric symptom severity scores.
AB - BACKGROUND: The CEGS N-GRID 2016 Shared Task in Clinical Natural Language
Processing (NLP) provided a set of 1000 neuropsychiatric notes to participants as
part of a competition to predict psychiatric symptom severity scores. This paper
summarizes our methods, results, and experiences based on our participation in
the second track of the shared task. OBJECTIVE: Classical methods of text
classification usually fall into one of three problem types: binary, multi-class,
and multi-label classification. In this effort, we study ordinal regression
problems with text data where misclassifications are penalized differently based
on how far apart the ground truth and model predictions are on the ordinal scale.
Specifically, we present our entries (methods and results) in the N-GRID shared
task in predicting research domain criteria (RDoC) positive valence ordinal
symptom severity scores (absent, mild, moderate, and severe) from psychiatric
notes. METHODS: We propose a novel convolutional neural network (CNN) model
designed to handle ordinal regression tasks on psychiatric notes. Broadly
speaking, our model combines an ordinal loss function, a CNN, and conventional
feature engineering (wide features) into a single model which is learned end-to
end. Given interpretability is an important concern with nonlinear models, we
apply a recent approach called locally interpretable model-agnostic explanation
(LIME) to identify important words that lead to instance specific predictions.
RESULTS: Our best model entered into the shared task placed third among 24 teams
and scored a macro mean absolute error (MMAE) based normalized score (100.(1
MMAE)) of 83.86. Since the competition, we improved our score (using basic
ensembling) to 85.55, comparable with the winning shared task entry. Applying
LIME to model predictions, we demonstrate the feasibility of instance specific
prediction interpretation by identifying words that led to a particular decision.
CONCLUSION: In this paper, we present a method that successfully uses wide
features and an ordinal loss function applied to convolutional neural networks
for ordinal text classification specifically in predicting psychiatric symptom
severity scores. Our approach leads to excellent performance on the N-GRID shared
task and is also amenable to interpretability using existing model-agnostic
approaches.
PMID- 28506906
TI - Controlling liver cancer mortality on a global scale: Still a long way to go.
PMID- 28506905
TI - Eight millimetre covered TIPS does not compromise shunt function but reduces
hepatic encephalopathy in preventing variceal rebleeding.
AB - BACKGROUND & AIMS: Currently, there are no recommendations in guidelines
concerning the preferred diameter of stents for transjugular intrahepatic
portosystemic shunt (TIPS), owing to the lack of adequate evidence. We therefore
compared 8mm stents with 10mm stents, to evaluate whether 8mm stents would
achieve similar shunt function, with less hepatic encephalopathy (HE) and better
liver function. METHODS: Cirrhotic patients were randomly assigned to receive
TIPS with an 8mm or 10mm covered stent to prevent variceal rebleeding. The
primary endpoint was shunt dysfunction. All-cause rebleeding, orthotopic liver
transplantation (OLT)-free survival, their composite endpoint, overt HE (overall
and spontaneous) and liver function were designated as the secondary endpoints.
RESULTS: From July 2012 to January 2014, 64 and 63 patients were allocated to the
8mm and 10mm groups, respectively. During a median follow-up of 27months in both
arms, dysfunction rates (16% vs. 16% at two years, p=0.62), two-year rebleeding
(16% vs. 17%, p=0.65), OLT-free survival (95% vs. 86%, p=0.37), and the composite
endpoint (p=0.62) were not statistically different between the groups. Despite a
marginal decrease in overall overt HE, there were significantly fewer spontaneous
overt HE incidents in the 8mm group within two years (27% vs. 43%, p=0.03), with
a risk reduction of 47%. Notably, patients receiving 8mm stents also developed
less hepatic impairment. CONCLUSIONS: TIPS with 8mm covered stents showed similar
shunt function to TIPS with 10mm stents, but halved the risk of spontaneous overt
HE and reduced hepatic impairment. Therefore, 8mm TIPS stents should be preferred
for the prevention of variceal rebleeding in cirrhotic patients. Lay summary: The
optimal diameter for transjugular intrahepatic portosystemic shunt (TIPS)
remained uncertain. This study showed that TIPS with 8mm covered stents did not
compromise shunt patency, or influence the efficacy of variceal rebleeding
prevention compared to TIPS with 10mm stents, but reduced the risk of spontaneous
overt hepatic encephalopathy and the incidence of severe encephalopathy.
Moreover, liver function reserve was also better in the 8mm stents group,
suggesting that 8mm TIPS stents should be preferred for the prevention of
variceal rebleeding in cirrhotic patients.
PMID- 28506907
TI - Validity criteria for the diagnosis of fatty liver by M probe-based controlled
attenuation parameter.
AB - BACKGROUND & AIMS: Controlled attenuation parameter (CAP) can be performed
together with liver stiffness measurement (LSM) by transient elastography (TE)
and is often used to diagnose fatty liver. We aimed to define the validity
criteria of CAP. METHODS: CAP was measured by the M probe prior to liver biopsy
in 754 consecutive patients with different liver diseases at three centers in
Europe and Hong Kong (derivation cohort, n=340; validation cohort, n=414; 101
chronic hepatitis B, 154 chronic hepatitis C, 349 non-alcoholic fatty liver
disease, 37 autoimmune hepatitis, 49 cholestatic liver disease, 64 others; 277 F3
4; age 52+/-14; body mass index 27.2+/-5.3kg/m2). The primary outcome was the
diagnosis of fatty liver, defined as steatosis involving >=5% of hepatocytes.
RESULTS: The area under the receiver-operating characteristics curve (AUROC) for
CAP diagnosis of fatty liver was 0.85 (95% CI 0.82-0.88). The interquartile range
(IQR) of CAP had a negative correlation with CAP (r=-0.32, p<0.001), suggesting
the IQR-to-median ratio of CAP would be an inappropriate validity parameter. In
the derivation cohort, the IQR of CAP was associated with the accuracy of CAP
(AUROC 0.86, 0.89 and 0.76 in patients with IQR of CAP <20 [15% of patients], 20
39 [51%], and >=40dB/m [33%], respectively). Likewise, the AUROC of CAP in the
validation cohort was 0.90 and 0.77 in patients with IQR of CAP <40 and >=40dB/m,
respectively (p=0.004). The accuracy of CAP in detecting grade 2 and 3 steatosis
was lower among patients with body mass index >=30kg/m2 and F3-4 fibrosis.
CONCLUSIONS: The validity of CAP for the diagnosis of fatty liver is lower if the
IQR of CAP is >=40dB/m. Lay summary: Controlled attenuation parameter (CAP) is
measured by transient elastography (TE) for the detection of fatty liver. In this
large study, using liver biopsy as a reference, we show that the variability of
CAP measurements based on its interquartile range can reflect the accuracy of
fatty liver diagnosis. In contrast, other clinical factors such as adiposity and
liver enzyme levels do not affect the performance of CAP.
PMID- 28506908
TI - Effects of the fibroblast activation protein inhibitor, PT100, in a murine model
of pulmonary fibrosis.
AB - Bleomycin (BLM) induced lung injury is detectable in C57BL/6 mice using magnetic
resonance imaging (MRI). We investigated the effects of the fibroblast activation
protein (FAP) inhibitor, PT100, in this model. BLM (0.5mg/kg/day) was
administered on days -7, -6, -5, -2, -1, 0 in the nostrils of male mice. PT100
(40ug/mouse) or vehicle (0.9%NaCl) was dosed per os twice daily from day 1-14.
MRI was performed before BLM and at days 0, 7 and 14. After the last MRI
acquisition, animals were euthanised and the lungs harvested for histological and
quantitative real-time polymerase chain reaction (qRT-PCR) analyses. As evidenced
longitudinally by MRI, the BLM-elicited lesions in the lungs of vehicle-treated
mice progressed over time. In contrast, responses elicited by BLM did not
progress in animals receiving PT100. Histology demonstrated significant less
fibrosis in PT100- than in vehicle-treated, BLM-challenged mice. Significant
correlation (R=0.91, P<0.001, N=24) was found between the volumes of BLM-induced
lesions detected in vivo by MRI and the collagen content determined
histologically (picrosirius staining). FAP was overexpressed in the lungs of BLM
challenged mice. Upon PT100 treatment, FAP expression was reduced. Significant
differences in the MMP-12, MIP-1alpha, and MCP-3 mRNA expression levels in the
lungs of PT100- compared to vehicle-treated mice were also revealed by qRT-PCR.
The IBA-1 level determined histologically was higher in the lungs of PT100-
compared to vehicle-treated mice. Taken together, these observations suggest that
treatment with PT100 in this murine model of pulmonary fibrosis had an anti-fibro
proliferative effect and increased macrophage activation.
PMID- 28506909
TI - The selective effect of glycyrrhizin and glycyrrhetinic acid on topoisomerase
IIalpha and apoptosis in combination with etoposide on triple negative breast
cancer MDA-MB-231 cells.
AB - Triple negative breast cancer(TNBC) has generated growing interests due to its
aggressive biologic behavior and absence of targeted therapy approach.
Glycyrrhizin(GL) from licorice root and its metabolite, glycyrrhetinic acid(GA)
have shown extensive bioactivities in clinic. Here, we demonstrate that GL and GA
have contrary anti-cancer effect on TNBC MDA-MB-231 cells. Beside its inhibition
of cell proliferation, GA at non-cytotoxic concentration showed synergistic
effect in combination with anti-cancer drug, etoposide(VP-16). Specifically, GA
enhanced cytotoxicity through regulating topoisomerase IIalpha(TOPO 2A) targeted
by etoposide. GA sensitized the cells to etoposide through elevating TOPO 2A with
a 2.4 fold rate at 12h. From 12 to 48h, GA halved the expression of TOPO 2A and
stimulated apoptosis, which exhibited its antineoplastic effect. Our experiments
showed that GSH depletion, modulation of MAPK and AKT pathways accounted for the
regulation of topoisomerase IIalpha and apoptosis. However, GL showed protection
and detoxication by decreasing reactive oxygen species generation, maintaining
GSH and differentially modulating apoptosis, AKT pathway, ERK and JNK of MAPK
pathway. Collectively, our results demonstrate that GA, instead of GL, is a
better candidate for TNBC treatment because of its anti-cancer effect and
sensitization of topoisomerase IIalpha inhibitor.
PMID- 28506910
TI - Omecamtiv mecarbil activates ryanodine receptors from canine cardiac but not
skeletal muscle.
AB - Due to the limited results achieved in the clinical treatment of heart failure, a
new inotropic strategy of myosin motor activation has been developed. The lead
molecule of myosin activator agents is omecamtiv mecarbil, which binds directly
to the heavy chain of the cardiac beta-myosin and enhances cardiac contractility
by lengthening the lifetime of the acto-myosin complex and increasing the number
of the active force-generating cross-bridges. In the absence of relevant data,
the effect of omecamtiv mecarbil on canine cardiac ryanodine receptors (RyR 2)
has been investigated in the present study by measuring the electrical activity
of single RyR 2 channels incorporated into planar lipid bilayer. When applying
100nM Ca2+ concentration on the cis side ([Ca2+]cis) omecamtiv mecarbil (1-10uM)
significantly increased the open probability and opening frequency of RyR 2,
while the mean closed time was reduced. Mean open time was increased moderately
by 10uM omecamtiv mecarbil. When [Ca2+]cis was elevated to 322 and 735nM, the
effect of omecamtiv mecarbil on open probability was evident only at higher (3
10uM) concentrations. All effects of omecamtiv mecarbil were fully reversible
upon washout. Omecamtiv mecarbil (up to 10uM) had no effect on the open
probability of RyR 1, isolated from either canine or rabbit skeletal muscles. It
is concluded that the direct stimulatory action of omecamtiv mecarbil on RyR 2
has to be taken into account when discussing the mechanism of action or the
potential side effects of the compound.
PMID- 28506911
TI - Mangiferin protects against ?intestinal ischemia/reperfusion-induced ?liver
injury: ??Involvement of PPAR-?gamma, GSK-3beta and Wnt/beta-catenin
pathway????????????????????????????????????????????????.
AB - AIM: Mangiferin (MF), a xanthonoid from Mangifera indica, possesses anti
inflammatory, immunomodulatory, and potent antioxidant effects; however, its
protective effect against mesenteric ischemia/reperfusion (I/R)-induced liver
injury has not been fully clarified. The study was designed to assess the
possible mechanism of action of MF against mesenteric I/R model. MAIN METHODS:
Male Wister rats were treated with MF (20mg/kg, i.p) or the vehicle for 3 days
before I/R, which was induced by clamping the superior mesenteric artery for
30min followed by declamping for 60min. KEY FINDINGS: The mechanistic studies
revealed that MF protected the 2 organs studied, viz., liver and intestine partly
via increasing the content of beta-catenin and PPAR-gamma along with decreasing
that of GSK-3beta and the phosphorylated NF-?B-p65. MF antioxidant effect was
evidenced by increasing contents of total antioxidant capacity and GST, besides
normalizing that of MDA. Regarding the anti-inflammatory effect, MF reduced IL
1beta and IL-6, effects that were mirrored on the tissue content of MPO.
Moreover, MF possessed anti-apoptotic character evidenced by elevating Bcl-2
content and reducing that of caspase-3. In the serum, intestinal I/R increased
the activity of ALT, AST, and creatine kinase. SIGNIFICANCE: The intimated
protective mechanisms of MF against mesenteric I/R are mediated, partially, by
modulation of oxidative stress, inflammation, and apoptosis possibly via the
involvement of Wnt/beta-catenin/NF-?beta/ PPAR-gamma signaling pathways.
PMID- 28506912
TI - Characterization and comparison of SGLT2 inhibitors: Part 3. Effects on diabetic
complications in type 2 diabetic mice.
AB - In this study, we investigated and compared the effects of all six sodium-glucose
cotransporter (SGLT) 2 inhibitors commercially available in Japan on diabetes
related diseases and complications in type 2 diabetic mice. Following 4-week
repeated administration to diabetic mice, all SGLT2 inhibitors showed significant
improvement in diabetes-related diseases and complications, including obesity;
abnormal lipid metabolism; steatohepatitis; inflammation; endothelial
dysfunction; and nephropathy. While all SGLT2 inhibitors exerted comparable
effects in reducing hyperglycemia, improvement of these diabetes-related diseases
and complications was more potent with the two long-acting drugs (ipragliflozin
and dapagliflozin) than with the four intermediate-acting four drugs
(tofogliflozin, canagliflozin, empagliflozin, and luseogliflozin), albeit without
statistical significance. These findings demonstrate that SGLT2 inhibitors
alleviate various diabetic pathological conditions in type 2 diabetic mice, and
suggest that SGLT2 inhibitors, particularly long-acting drugs, might be useful
not only for hyperglycemia but also in diabetes-related diseases and
complications, including nephropathy in type 2 diabetes.
PMID- 28506914
TI - Compliant endovascular balloon reduces the lethality of superior vena cava tears
during transvenous lead extractions.
AB - BACKGROUND: Superior vena cava (SVC) lacerations have been identified as the most
lethal complication encountered during cardiac implantable electronic device lead
extraction. The case fatality rate of these events approximates 50% due to rapid
exsanguination. A novel, compliant balloon specifically designed for use in the
SVC may provide hemostasis in the event of endovascular perforation. By
temporarily occluding the compromised vessel, the endovascular balloon should
delay hemodynamic collapse, provide a more controlled surgical field for repair,
and thereby reduce the mortality of SVC tears complicating transvenous lead
extraction. OBJECTIVE: To assess the early impact of the compliant endovascular
balloon on the management of SVC tears and survival outcomes. METHODS: We
searched a publicly available, United States Food and Drug Administration
maintained database for adverse events from 1 manufacturer of lead extraction
tools. Reports from July 1, 2016, to December 31, 2016 were reviewed by 2
physicians to identify instances of SVC tears. Extracting physicians were
contacted for further case details. Confirmed SVC tears were analyzed for patient
demographics, repair strategies, and index hospitalization mortality. RESULTS: Of
the complications reported, 35 cases of surgically confirmed SVC tears were
identified. One hundred percent of patients (9/9) were discharged alive when the
endovascular balloon was properly utilized, compared to 50% of patients (13/26)
when the device was not used (P = .0131). Differences between all other variables
analyzed were statistically insignificant. CONCLUSION: During the study period,
we observed a reduction in mortality in patients who suffered SVC tears while
undergoing lead extraction when treatment included an endovascular balloon.
PMID- 28506913
TI - Predicting Determinants of Atrial Fibrillation or Flutter for Therapy Elucidation
in Patients at Risk for Thromboembolic Events (PREDATE AF) Study.
AB - BACKGROUND: Atrial fibrillation (AF) is the most common clinically significant
cardiac rhythm disorder. There is considerable interest in screening for AF, as
it is a leading cause of stroke, and oral anticoagulants (OACs) have been shown
to significantly reduce the risk of stroke in patients with AF. Improved
screening for AF with subsequent treatment may help improve long-term outcomes,
but the optimal patient population and screening intensity are unknown.
OBJECTIVES: In this study, we prospectively evaluated the use of the CHA2DS2-VASc
score for the prediction of new-onset AF using insertable cardiac monitors (ICMs)
and examined whether this screening led to the initiation of OAC therapy.
METHODS: We enrolled 245 subjects with no history of AF and CHA2DS2-VASc score
>=2 to be screened for AF with an ICM. The ICMs were programmed to record AF
episodes >=6 minutes in duration. Subjects were followed for 18 months with
monthly remote interrogations and all events adjudicated by cardiologists. In
subjects diagnosed with AF, medical records were reviewed to determine subsequent
care. RESULTS: During a mean follow-up of 451 +/- 185 days, the incidence of AF
was 22.4% (95% confidence interval 17.2%-27.7%) with a mean time to detection of
141.3 +/- 139.5 days. Among subjects newly diagnosed with AF, 76.4% were
prescribed anticoagulation with either a novel OAC (n = 38) or warfarin (n = 4).
CONCLUSION: In this large prospective cohort of subjects with CHA2DS2-VASc scores
>=2, 22.4% were newly diagnosed with AF and the majority of these subjects were
given OACs, suggesting a potential role of ICMs in AF screening.
PMID- 28506915
TI - Long QT syndrome: Who needs a transplant?
PMID- 28506918
TI - Cardiac resynchronization therapy using permanent His-bundle pacing: Are we there
yet?
PMID- 28506917
TI - Atrial antitachycardia pacing and atrial remodeling: A substudy of the
international, randomized MINERVA trial.
AB - BACKGROUND: Atrial tachycardia (AT) and atrial fibrillation (AF) are common in
pacemaker patients and are associated with bad prognoses. OBJECTIVE: The purpose
of this study was to evaluate atrial antitachycardia pacing impact on AT/AF
induced atrial remodeling, measured by early recurrence of AT/AF (ERAF) and by
change in left atrial diameter (LAD), and to evaluate the impact of AT/AF
duration on ERAF incidence. METHODS: Pacemaker patients were randomized to dual
chamber pacing (Control DDDR: 385 patients), managed ventricular pacing (MVP: 398
patients), or atrial antitachycardia pacing plus MVP (DDDRP+MVP: 383 patients).
LAD change, estimated by echocardiography, was considered significant if the
relative difference between baseline and 24-month measurements was >10%. RESULTS:
At median follow-up of 34 months, ERAF incidence was significantly lower in the
DDDRP+MVP arm for all AT/AF durations, in particular, ERAF followed AT/AF longer
than 3 hours in 53% cases in Control DDDR, in 51% cases in MVP, and in 39% cases
in DDDRP+MVP (P <.001 vs other groups). ERAF incidence showed a U-shaped pattern
when evaluated as a function of previous AT/AF duration, decreasing for durations
from 5 minutes to 12 hours and increasing for longer durations. Among patients
with significant LAD change, the proportion of patients with a reduction in LAD
was 35% in Control DDDR, 37% in MVP, and 70% in DDDRP+MVP (P <.05 vs other
groups). CONCLUSION: Our data suggest that atrial electrical remodeling becomes
important after about 12 hours of continuous arrhythmia. Compared to DDDR or MVP,
DDDRP+MVP reduces ERAF and favors LAD reduction, suggesting that atrial
antitachycardia pacing may reverse electrical and mechanical remodeling.
PMID- 28506919
TI - Novel dyeless and fluoro-less approach to cryoballoon pulmonary vein occlusion
assessment.
AB - BACKGROUND: Pulmonary vein (PV) occlusion is essential for PV isolation (PVI)
using the cryoballoon. Currently occlusion is arbitrarily determined using
fluoroscopy and contrast media. This study aimed to create an objective measure
without utilizing excessive fluoroscopy and using no contrast media. OBJECTIVE:
To ensure PV occlusion without fluoroscopy and contrast dye. METHODS: In 4 in
vivo hearts 113 PV occlusions were tested with a 50% cold dye saline mix at 4
degrees C. Occlusions were rated Good, Fair, and Poor by dye dissipation seen via
fluoroscopy and correlated to temperature profiles recorded concurrently. Using
these temperature profiles and no dye, cryoablations were placed in 12 additional
hearts (56 unique veins, 126 occlusions). Two 180-second cryoablation
applications were placed per vein with occlusion testing in between. PVI was
defined by electrophysiology mapping, gross pathology, and histology after >=4
weeks recovery. RESULTS: Dye results were as follows: With Good, Fair, and Poor
the maximal postinjection PV temperature dropped (DeltaT) by 6.2 +/- 4.2 degrees
C, 5.1 +/- 3.7 degrees C, and 2.4 +/- 2.0 degrees C. At 5 seconds post nadir
temperature, injection temperature recovered 18% +/- 14%, 36% +/- 23%, and 50% +/
33%. Console thaw time to 0 degrees C was 11.5 +/- 4.8 seconds, 8.5 +/- 2.1
seconds, and 4.3 +/- 1.3 seconds. Success rate for PVI was 100%, 97%, and 0%.
With no dye: DeltaT: 7.7 +/- 4.4 degrees C, 5.8 +/- 5.0 degrees C, and 3.4 +/-
2.3 degrees C; % recovery at 5 seconds: 15% +/- 12%, 31% +/- 23%, 45% +/- 30%;
thaw time to 0 degrees C: 11.9 +/- 4.8 seconds, 10.5 +/- 5.2 seconds, 6.0 +/- 2.8
seconds; success rate: 97%, 91%, and 10%. CONCLUSION: PV occlusion profile
determination using 4 degrees C cold saline injection is an effective approach to
define the occlusion grade. Quality occlusions correlate strongly with PVI
success.
PMID- 28506920
TI - Regulatory B cells in rheumatoid arthritis: Alterations in patients receiving
anti-TNF therapy.
AB - : Cytokines, including tumor necrosis factor alpha (TNFalpha) are involved in
Rheumatoid arthritis (RA) pathogenesis by augmenting autoimmunity, sustaining
long term inflammation in the synovium, and promoting joint damage. Anti-TNF
therapy is one of the most efficient and widely used therapies for RA, although
its mechanism is not clarified yet. Earlier we demonstrated that RA patients have
a reduced number of IL-10 producing regulatory B cells (B10 cells) as compared to
healthy individuals and they are functionally impaired. Our aim was to study the
influence of anti-TNF therapy on B10 cells in RA, to follow the alteration of B
cell activation markers (CD25, CD69) and to monitor the level of citrullinated
peptid-specific antibodies and the secreted IL-10 in patients' sera during the
therapy. We have observed that at six month after starting the therapy the
frequency of B10 cells remarkably increased, while the expression of the
activation marker, CD69 decreased on B cells. In contrast, serum levels of IL-10
and anti-citrullinated peptide antibodies did not change post-treatment.
CONCLUSION: The reduced activation state of B cells and the increasing number of
regulatory B10. cells might contribute to the therapeutic efficacy of anti-TNF
agents in RA.
PMID- 28506921
TI - Decrease of blood anti-alpha1,3 Galactose Abs levels in multiple sclerosis (MS)
and clinically isolated syndrome (CIS) patients.
AB - The etiology of multiple sclerosis (MS) remains elusive. Among the possible
causes, the increase of anti-Neu5Gc antibodies during EBV primo-infection of
Infectious mononucleosis (IMN) may damage the integrity of the blood-brain
barrier facilitating the transfer of EBV-infected B cells and anti-EBV T cell
clones in the brain. We investigated the change in titers of anti-Neu5Gc and anti
alpha1,3 Galactose antibodies in 49 IMN, in 76 MS, and 73 clinically isolated
syndrome (CIS) patients, as well as age/gender-matched healthy individuals. Anti
Gal and anti-Neu5Gc are significantly increased during IMN (p=0.02 and p<1.10-4
respectively), but not in acute CMV primo-infection. We show that, whereas there
was no change in anti-Neu5Gc in MS/CIS, the two populations exhibit a significant
decrease in anti-Gal (combined p=2.7.10-3), in contrast with patients with non
MS/CIS central nervous system pathologies. Since anti-Gal result from an
immunization against alpha1,3 Gal, lacking in humans but produced in the gut, our
data suggest that CIS and MS patients have an altered microbiota or an altered
response to this microbiotic epitope.
PMID- 28506923
TI - Core, social and moral disgust are bounded: A review on behavioral and neural
bases of repugnance in clinical disorders.
AB - Disgust is a multifaceted experience that might affect several aspects of life.
Here, we reviewed research on neurological and psychiatric disorders that are
characterized by abnormal disgust processing to test the hypothesis of a shared
neurocognitive architecture in the representation of three disgust domains: i)
personal experience of 'core disgust'; ii) social disgust, i.e., sensitivity to
others' expressions of disgust; iii) moral disgust, i.e., sensitivity to ethical
violations. Our review provides some support to the shared neurocognitive
hypothesis and suggests that the insula might be the "hub" structure linking the
three domains of disgust sensitivity, while other brain regions may subserve
specific facets of the multidimensional experience. Our review also suggests a
role of serotonin core and moral disgust, supporting "neo-sentimentalist"
theories of morality, which posit a causal role of affect in moral judgment.
PMID- 28506924
TI - Olfactory and gustatory functions in bipolar disorders: A systematic review.
AB - Olfactory and gustatory dysfunctions have been described in different psychiatric
disorders. Several studies have found gustatory and olfactory function change in
bipolar disorders with various results. The aim of this study is to have a
systematic review of studies evaluating gustatory and olfactory function in
bipolar disorders. After a systematic search, 15 studies on olfaction and 5
studies on taste were included in this review. The UPSIT (University of
Pennsylvania Smell Identification Test) and Sniffin' Sticks were the most widely
used tests to evaluate smell. Some studies on olfaction described dysfunctions in
smell identification as potential markers for bipolar disorders. Moreover,
olfactory acuity was associated with psychosocial and cognitive performances. For
taste, only few studies used standardized tests to evaluate gustation. These
studies showed that patients with Bipolar disorders had more gustatory
dysfunction compared to controls, and to non-bipolar depressed patients.
PMID- 28506925
TI - Social connectedness, mental health and the adolescent brain.
AB - Social relationships promote health and wellbeing. Brain regions regulating
social behavior continue to develop throughout adolescence, as teens learn to
navigate their social environment with increasing sophistication. Adolescence is
also a time of increased risk for the development of psychiatric disorders, many
of which are characteristically associated with social dysfunction. In this
review, we consider the links between adolescent brain development and the
broader social environment. We examine evidence that individual differences in
social ability, partly determined by genetic influences on brain structure and
function, impact the quality and quantity of social ties during adolescence and
that, conversely, the structure of one's social network exerts complex yet
profound influences on individual behavior and mental health. In this way, the
brain and social environment sculpt each other throughout the teenage years to
influence one's social standing amongst peers. Reciprocal interactions between
brain maturation and the social environment at this critical developmental stage
may augment risk or promote resilience for mental illness and other health
outcomes.
PMID- 28506927
TI - Connecting minds and sharing emotions through mimicry: A neurocognitive model of
emotional contagion.
AB - During social interactions, people tend to automatically align with, or mimic
their interactor's facial expressions, vocalizations, postures and other bodily
states. Automatic mimicry might be implicated in empathy and affiliation and is
impaired in several pathologies. Despite a growing body of literature on its
phenomenology, the function and underlying mechanisms of mimicry remain poorly
understood. The current review puts forward a new Neurocognitive Model of
Emotional Contagion (NMEC), demonstrating how basic automatic mimicry can give
rise to emotional contagion. We combine neurological, developmental and
evolutionary insights to argue that automatic mimicry is a precursor to healthy
social development. We show that (i) strong synchronization exists between
people, (ii) that this resonates on different levels of processing and (iii)
demonstrate how mimicry translates into emotional contagion. We conclude that our
synthesized model, built upon integrative knowledge from various fields, provides
a promising avenue for future research investigating the role of mimicry in human
mental health and social development.
PMID- 28506922
TI - Oxytocin effects in schizophrenia: Reconciling mixed findings and moving forward.
AB - Schizophrenia is a severe mental illness that causes major functional impairment.
Current pharmacologic treatments are inadequate, particularly for addressing
negative and cognitive symptoms of the disorder. Oxytocin, a neuropeptide known
to moderate social behaviors, has been investigated as a potential therapeutic
for schizophrenia in recent years. Results have been decidedly mixed, leading to
controversy regarding oxytocin's utility. In this review, we outline several
considerations for interpreting the extant literature and propose a focused
agenda for future work that builds on the most compelling findings regarding
oxytocin effects in schizophrenia to date. Specifically, we examine underlying
causes of heterogeneity in randomized clinical trials (RCTs) conducted thus far
and highlight the complexity of the human oxytocin system. We then review
evidence of oxytocin's effects on specific deficits in schizophrenia, arguing for
further study using objective, precise outcome measures in order to determine
whether oxytocin has the potential to improve functional impairment in
schizophrenia.
PMID- 28506928
TI - Distinct phosphodiesterase 5A-containing compartments allow selective regulation
of cGMP-dependent signalling in human arterial smooth muscle cells.
AB - Cyclic GMP (cGMP) translates and integrates much of the information encoded by
nitric oxide (NO.) and several natriuretic peptides, including the atrial
natriuretic peptide (ANP). Previously, we reported that integration of a cGMP
specific cyclic nucleotide phosphodiesterase, namely phosphodiesterase 5A
(PDE5A), into a protein kinase G (PKG)- and inositol-1,4,5-trisphosphate receptor
(IP3R)-containing endoplasmic reticulum (ER) signalosome allows localized control
of PDE5A activity and of PKG-dependent inhibition of IP3-mediated release of ER
Ca2+ in human platelets. Herein, we report that PDE5A integrates into an
analogous signalosome in human arterial smooth muscle cells (HASMC), wherein it
regulates muscarinic agonist-dependent Ca2+ release and is activated selectively
by PKG-dependent phosphorylation. In addition, we report that PDE5A also
regulates HASMC functions via events independent of PKG, but rather through
actions coordinated by competitive cGMP-mediated inhibition of cAMP hydrolysis by
the so-called cGMP-inhibited cAMP PDE, namely phosphodiesterase 3A (PDE3A).
Indeed, we show that ANP increases both cGMP and cAMP levels in HASMC and
promotes phosphorylation of vasodilator-stimulated phospho-protein (VASP) at each
the PKG and PKA phospho-acceptor sites. Since selective inhibition of PDE5
decreased DNA synthesis and chemotaxis of HASMC, and that PDE3A knockdown
obviated these effects, our findings are consistent with a role for a PDE5A-PDE3A
PKA axis in their regulation. Our findings provide insight into the existence of
distinct "pools" of PDE5A in HASMC and support the idea that these discrete
compartments regulate distinct cGMP-dependent events. As a corollary, we suggest
that it may be possible to target these distinct PDE5A-regulated pools and in so
doing differentially impact selected cGMP-regulated functions in these cells.
PMID- 28506926
TI - High times for cannabis: Epigenetic imprint and its legacy on brain and behavior.
AB - Extensive debates continue regarding marijuana (Cannabis spp), the most commonly
used illicit substance in many countries worldwide. There has been an exponential
increase of cannabis studies over the past two decades but the drug's long-term
effects still lack in-depth scientific data. The epigenome is a critical
molecular machinery with the capacity to maintain persistent alterations of gene
expression and behaviors induced by cannabinoids that have been observed across
the individual's lifespan and even into the subsequent generation. Though
mechanistic investigations regarding the consequences of developmental cannabis
exposure remain sparse, human and animal studies have begun to reveal specific
epigenetic disruptions in the brain and the periphery. In this article, we focus
attention on long-term disturbances in epigenetic regulation in relation to
prenatal, adolescent and parental germline cannabinoid exposure. Expanding
knowledge about the protracted molecular memory could help to identify novel
targets to develop preventive strategies and treatments for behaviors relevant to
neuropsychiatric risks associated with developmental cannabis exposure.
PMID- 28506929
TI - Inhibition of cell proliferation and induction of autophagy by KDM2B/FBXL10
knockdown in gastric cancer cells.
AB - Gastric cancer is difficult to cure due to its clinical heterogeneity and the
complexity of its molecular mechanisms. KDM2B, a member of the JHDM family,
functions as a histone lysine demethylase. However, the role and mechanisms of
KDM2B in gastric cancer have not been elucidated. Here, we showed that KDM2B is
commonly expressed in gastric cancer cells. The downregulation of KDM2B
immediately induces autophagy, followed by the inhibition of proliferation. The
compound 3-methyladenine (3-MA), an inhibitor of autophagy, largely rescues
autophagy and the inhibition of cell proliferation induced by KDM2B knockdown. In
this process, we observed a downregulation of the phosphorylation of Akt and its
downstream effectors mTOR and p70S6K and an upregulation of Erk phosphorylation
after KDM2B knockdown. In a xenograft model, the downregulation of KDM2B can
inhibit tumour growth. The conversion of LC3-I to LC3-II also decreased
concomitantly in vivo, which is a hallmark of autophagy. Taken together, our
study was the first to demonstrate a novel regulatory role of KDM2B in autophagy
and cell growth in gastric cancer cells. Our findings suggest that KDM2B may
serve as a novel therapeutic target for gastric cancer therapy.
PMID- 28506931
TI - In vitro affinity of Deinococcus radiodurans MutS towards mismatched DNA exceeds
that of its orthologues from Escherichia coli and Thermus thermophilus.
AB - The mismatch binding protein MutS is responsible for the recognition of mispaired
and unpaired bases, which is the initial step in DNA repair. Among the MutS
proteins most extensively studied in vitro are those derived from Thermus
thermophilus, Thermus aquaticus and Escherichia coli. Here, we present the first
report on the in vitro examination of DNA mismatch binding activity of MutS
protein from Deinococcus radiodurans and confront this with the properties of
those from E. coli and T. thermophilus. The analyses which included mobility gel
shift assay, colorimetric and qPCR estimation of MutS-bound DNA clearly showed
that D. radiodurans MutS exhibited much higher affinity towards mismatched DNA in
vitro than its counterparts from E. coli and T. thermophilus. In addition, D.
radiodurans MutS displayed a significantly higher specificity of DNA mismatch
binding than the two other orthologues. The specificity expressed as the ratio of
mismatched to fully complementary DNA bound reached over 4 and 20-fold higher
values for D. radiodurans than for T. thermophilus and E. coli MutS,
respectively. The results demonstrate mainly the biotechnological potential of D.
radiodurans MutS but the in vitro characteristics of the MutS orthologues could
reflect substantial differences in DNA mismatch binding activities existing in
vivo.
PMID- 28506930
TI - Rewiring the reductive tricarboxylic acid pathway and L-malate transport pathway
of Aspergillus oryzae for overproduction of L-malate.
AB - Aspergillus oryzae finds wide application in the food, feed, and wine industries,
and is an excellent cell factory platform for production of organic acids. In
this work, we achieved the overproduction of L-malate by rewiring the reductive
tricarboxylic acid (rTCA) pathway and L-malate transport pathway of A. oryzae
NRRL 3488. First, overexpression of native pyruvate carboxylase and malate
dehydrogenase in the rTCA pathway improved the L-malate titer from 26.1gL-1 to
42.3gL-1 in shake flask culture. Then, the oxaloacetate anaplerotic reaction was
constructed by heterologous expression of phosphoenolpyruvate carboxykinase and
phosphoenolpyruvate carboxylase from Escherichia coli, increasing the L-malate
titer to 58.5gL-1. Next, the export of L-malate from the cytoplasm to the
external medium was strengthened by overexpression of a C4-dicarboxylate
transporter gene from A. oryzae and an L-malate permease gene from
Schizosaccharomyces pombe, improving the L-malate titer from 58.5gL-1 to 89.5gL
1. Lastly, guided by transcription analysis of the expression profile of key
genes related to L-malate synthesis, the 6-phosphofructokinase encoded by the pfk
gene was identified as a potential limiting step for L-malate synthesis.
Overexpression of pfk with the strong sodM promoter increased the L-malate titer
to 93.2gL-1. The final engineered A. oryzae strain produced 165gL-1 L-malate with
a productivity of 1.38gL-1h-1 in 3-L fed-batch culture. Overall, we constructed
an efficient L-malate producer by rewiring the rTCA pathway and L-malate
transport pathway of A. oryzae NRRL 3488, and the engineering strategy adopted
here may be useful for the construction of A. oryzae cell factories to produce
other organic acids.
PMID- 28506932
TI - Refined annotation of the complete genome of the phytopathogenic and xanthan
producing Xanthomonas campestris pv. campestris strain B100 based on RNA sequence
data.
AB - Bioinformatics tools and gene expression data were applied to identify new genes
and to enhance the accuracy in genomic feature predictions for Xanthomonas
campestris pv. campestris (Xcc) B100, a pathogen of cruciferous plants and model
strain for the biosynthesis of xanthan, a polysaccharide with a multitude of
commercial applications as a thickening agent. Results from 5'-enriched end RNA
sequencing (RNA-seq) and total transcriptome RNA-seq experiments were used for
this purpose. Functional gene annotations were updated where new evidence had
emerged and start codon predictions were enhanced for 153 protein-coding genes
(CDS). In total, 32 novel CDS, and 176 novel RNA genes and features were
predicted, among them 77 isogenes of the small non-coding RNA sX9. Furthermore,
the RNA-seq data facilitated the identification of 848 operons that included a
total of 2551 CDS besides 1667 CDS that were mono-cistronically expressed.
PMID- 28506933
TI - Effective estimation of the minimum number of amino acid residues required for
functional divergence between duplicate genes.
AB - One of hot research foci has always been predicting amino acid residues
underlying functional divergence after gene duplication, as those predicted sites
can be used as candidates for further functional experimentations. It is
important and interesting to know how many sites, on average, may have been
responsible for the functional divergence between duplicate genes. In this
article, we studied two basic types of functional divergence (type-I and type-II)
in depth in order to give an accurate estimation of functional divergence-related
sites. Type-I divergences result from altered functional constraints (i.e.,
different evolutionary rates) between duplicate genes, whereas type-II
divergences refer to residues that are conserved by functional constraints but
exhibit different physicochemical properties (e.g., charge or hydrophobicity)
between duplicates. An effective site number (NE) strategy was applied in our
study, which implements a stepwise regression model to calculate the minimum
number of residues responsible for functional divergence without choosing preset
threshold. We found that NE-determined cut-off value varies among different
duplicate pairs, suggesting that empirical cutoff value is not suitable for every
case. Under our standard NE calculation method, we estimated less than 15% of
residues that are required for paralogous gene functional divergence. Finally, we
established a database, DIVERGE-D, as a public resource for the predicted NE
sites between two paralogs in this study, which can be used as candidates for
further biological engineering and experimentation.
PMID- 28506935
TI - Retrosynthesis of CaCO3 via amorphous precursor particles using gastroliths of
the Red Claw lobster (Cherax quadricarinatus).
AB - Gastroliths are highly calcified structures formed in the cardiac stomach wall of
crustaceans for the temporary storage of amorphous CaCO3 (ACC). The gastrolithic
ACC is stabilized by the presence of biomolecules, and represents a novel model
for research into biomineralization. For the first time, an in vitro biomimetic
retrosynthesis of scaffolds of gastrolithic matrices with CaCO3 is presented.
With the help of synthetic polyacrylic (PAA) and phytic (PA) acids, amorphous
precursor particles were stabilized in double (DD) and gas (GD) diffusion
crystallization assays. The presence of these synthetic molecules as efficient
inhibitors of nucleation and growth of CaCO3, and the use of biological
gastrolith scaffolds as confined reaction environments determined the kinetics of
crystallization, and controlled the morphogenesis of CaCO3. The formation of ACC
particles was demonstrated and their crystallization was followed by light
microscopy, scanning and transmission electron microscopy, and electron
diffraction.
PMID- 28506934
TI - Dynamic Regulation of DELLA Protein Activity: SPINDLY and SECRET AGENT Unmasked!
PMID- 28506936
TI - Assessment of long-term mortality in patients with complex coronary artery
disease undergoing percutaneous intervention: comparison of multiple anatomical
and clinical prognostic risk scores.
AB - AIMS: Three-vessel and left main coronary artery disease (CAD) have important
prognostic implications. Consequently, numerous risk scores have been developed
to stratify patients with complex CAD. The aim of the present study was to
compare the predictive performance of six risk scores for occurrence of fouryear
all-cause mortality. METHODS AND RESULTS: From March 2008 to December 2012, 348
consecutive patients with complex CAD undergoing percutaneous coronary
intervention (PCI) in a tertiary centre in Sao Paulo, Brazil, were analysed. Four
year mortality was assessed. The scores compared were: baseline SYNTAX score
(SS), residual SYNTAX score (rSS), ACEF score, clinical SYNTAX score (cSS),
SYNTAX revascularisation index (SRI) and SYNTAX score II (SSII). SSII had the
best predictive performance, AUC 0.82, Brier score 0.10, surpassing all the other
scores for long-term mortality prediction. Moreover, SSII discriminated well PCI
patients in risk groups with p<0.01 for four-year all-cause mortality. The ACEF
score (AUC 0.77) and the cSS (AUC 0.78) were significantly better than the SS
(AUC 0.65), SRI (AUC 0.60) or the rSS (AUC 0.55). CONCLUSIONS: For patients with
complex CAD treated by PCI, the combination of baseline clinical and angiographic
factors provided better risk assessment. The SSII demonstrated the most precise
predictive performance for long-term mortality.
PMID- 28506938
TI - Dynamic transcatheter mitral valve repair: a new concept to treat functional
mitral regurgitation using an adjustable spacer.
AB - We report the first-in-man implantation of the Mitra-Spacer. The device was
implanted transapically. FMR was reduced to moderate. At two months, while in
NYHA Class II, LVEF had improved, but FMR increased and 2 mL was added, reducing
FMR to mild. Despite anticoagulation, thrombi developed around the device and the
valve was replaced at eight months. The Mitra-Spacer successfully bridged this
patient to surgery after LVEF had recovered.
PMID- 28506937
TI - Bivalirudin infusion to reduce ventricular infarction: the open-label, randomised
Bivalirudin Infusion for Ventricular InfArction Limitation (BIVAL) study.
AB - AIMS: The aim of the study was to investigate whether bivalirudin versus
unfractionated heparin (UFH) reduces infarct size (IS) for primary percutaneous
coronary intervention (PPCI) in large acute myocardial infarction (AMI). METHODS
AND RESULTS: This multicentre open-label trial randomised 78 patients undergoing
PPCI for large AMI to bivalirudin or UFH. The primary endpoint was IS, assessed
by cardiac magnetic resonance (CMR) five days after PPCI. Secondary endpoints
included index of microcirculatory resistance (IMR), CMR-assessed microvascular
obstruction (MVO) and ejection fraction, and biomarkers for thrombin activity and
cell injury. No difference was observed in mean IS at five days (25.0+/-19.7 g
for bivalirudin vs. 27.1+/-20.7 g for UFH; p=0.75). Early MVO was numerically
lower with bivalirudin (5.3+/-5.8 g vs. 7.7+/-6.3 g; p=0.17), with no significant
difference in ejection fraction at 90 days (54.6+/-12.0% vs. 49.1+/-12.1%;
p=0.11). In the biomarkers, thrombin-antithrombin complexes were reduced by 4.8
ug/L over the first day for bivalirudin versus an increase of 1.9 ug/L in the
heparin arm (p=0.0003). Acute IMR was lower (43.5+/-21.6 vs. 68.7+/-35.8 mmHg*s,
respectively; p=0.014). In a planned interim analysis, an approximate 11%
reduction in IS was observed with bivalirudin; the trial was discontinued for
futility. CONCLUSIONS: This study did not achieve its primary endpoint of
significant infarct size reduction in PPCI by prolonged bivalirudin infusion
compared to UFH, even though complete thrombin inhibition was achieved in the
acute phase, with a lower myocardial microcirculation resistance at the end of
the procedure.
PMID- 28506939
TI - Printed MDCT 3D models for prediction of left atrial appendage (LAA) occluder
device size: a feasibility study.
AB - AIMS: Transoesophageal echocardiography (TEE) and multidetector computed
tomography (MDCT) currently serve as imaging modalities for left atrial appendage
(LAA) occlusion preprocedural planning. We assessed the feasibility of MDCT-based
models to predict the correct size of device for LAA occlusion procedures.
METHODS AND RESULTS: Patients planned for LAA occlusion underwent MDCT before
implantation, which was used for creating and printing 3D LAA models. Three
cardiologists evaluated the 3D models and predicted the correct size of the
device by manual manipulation. These predictions were compared with the actual
device implanted during the procedure. Twenty-nine patients were included in this
study. AMPLATZER and WATCHMAN devices were deployed in 12 and 17 patients,
respectively. Two procedures were aborted due to failure of occlusion; all three
physicians predicted it. There was good correlation between the 3D models and the
inserted device for AMPLATZER devices with a concordance correlation coefficient
of 0.778 (p=0.001) and poor agreement for WATCHMAN devices - concordance
correlation coefficient of 0.315 (p=0.203). Agreement among the three physicians
for AMPLATZER and WATCHMAN devices was excellent, with a calculated average intra
class correlation of 0.915 and 0.816, respectively. CONCLUSIONS: We found LAA
printed 3D models to be accurate for prediction of LAA occluder device size for
the AMPLATZER device but not for the WATCHMAN device.
PMID- 28506941
TI - Left distal transradial access in the anatomical snuffbox for coronary
angiography (ldTRA) and interventions (ldTRI).
AB - AIMS: The aim of this technical report is to demonstrate the feasibility of the
left distal transradial approach for patients in whom left radial access is
preferred over right radial access for coronary angiography and interventions.
This procedure is more convenient for the operator. For the right-handed patient,
the left radial access is more convenient because of the free use of the right
hand after the procedure. In addition, this technique reduces the chance of
radial artery occlusion at the site of the distal forearm. METHODS AND RESULTS:
Coronary access via the left distal radial artery at the anatomical snuffbox
allows comfortable positioning of the dorsal side of the patient's left hand near
the right groin. The operator can puncture the artery and perform the coronary
cannulation at a safe distance from the radiation source and without the need to
bend over the patient. This technique will be described in detail. Procedural and
clinical results in the first 70 patients are described. Out of 118 consecutive
patients assigned to the author's operation programme, 70 patients were
considered suitable for left distal radial access. There were eight procedural
failures, requiring crossover to traditional right radial or left radial
approach. All other procedures were successful, without major discomfort for the
patient and operator. No radial artery occlusions at the site of the forearm were
encountered. CONCLUSIONS: Left distal transradial coronary access via the
anatomical snuffbox, as default technique for patients who need or prefer left
radial access over right radial access, deserves further exploration.
PMID- 28506940
TI - COOL AMI EU pilot trial: a multicentre, prospective, randomised controlled trial
to assess cooling as an adjunctive therapy to percutaneous intervention in
patients with acute myocardial infarction.
AB - AIMS: We aimed to investigate the rapid induction of therapeutic hypothermia
using the ZOLL Proteus Intravascular Temperature Management System in patients
with anterior ST-elevation myocardial infarction (STEMI) without cardiac arrest.
METHODS AND RESULTS: A total of 50 patients were randomised; 22 patients (88%;
95% confidence interval [CI]: 69-97%) in the hypothermia group and 23 patients
(92%; 95% CI: 74-99) in the control group completed cardiac magnetic resonance
imaging at four to six days and 30-day follow-up. Intravascular temperature at
coronary guidewire crossing after 20.5 minutes of endovascular cooling decreased
to 33.6 degrees C (range 31.9-35.5 degrees C). There was a 17-minute (95% CI: 4.6
29.8 min) cooling-related delay to reperfusion. In "per protocol" analysis,
median infarct size/left ventricular mass was 16.7% in the hypothermia group
versus 23.8% in the control group (absolute reduction 7.1%, relative reduction
30%; p=0.31) and median left ventricular ejection fraction (LVEF) was 42% in the
hypothermia group and 40% in the control group (absolute reduction 2.4%, relative
reduction 6%; p=0.36). Except for self-terminating paroxysmal atrial fibrillation
(32% versus 8%; p=0.074), there was no excess of adverse events in the
hypothermia group. CONCLUSIONS: We rapidly and safely cooled patients with
anterior STEMI to 33.6 degrees C at the time of coronary guidewire crossing. This
is >=1.1 degrees C lower than in previous cooling studies. Except for self
terminating atrial fibrillation, there was no excess of adverse events and no
clinically important cooling-related delay to reperfusion. A statistically non
significant numerical 7.1% absolute and 30% relative reduction in infarct size
warrants a pivotal trial powered for efficacy.
PMID- 28506942
TI - Insights into the need for permanent pacemaker following implantation of the
repositionable LOTUS valve for transcatheter aortic valve replacement in 250
patients: results from the REPRISE II trial with extended cohort.
AB - AIMS: This analysis aimed to evaluate the incidence and predictors of the need
for permanent pacemaker (PPM) implantation following implantation of the
repositionable and fully retrievable LOTUS Aortic Valve Replacement System.
METHODS AND RESULTS: The prospective, single-arm, multicentre REPRISE II study
with extended cohort enrolled 250 symptomatic, high surgical risk patients with
severe aortic stenosis for transfemoral transcatheter aortic valve implantation
(TAVI) with a 23 mm or 27 mm LOTUS valve. Echocardiography, computed tomography,
and electrocardiography data were evaluated by independent core labs. Post TAVI,
32.0% (72/225) of pacemaker-naive patients underwent new PPM implantation at 30
days. Most (59/72, 82%) patients were implanted for third-degree atrioventricular
block, and >10% overstretch of the LVOT by area was observed in 59.7% (43/72) of
PPM patients. Significant independent predictors of PPM at 30 days included
baseline RBBB (odds ratio [OR] 12.7, 95% CI: 4.5, 36.2; p<0.001) and LVOT
overstretch >10% (OR 3.4, 95% CI: 1.7, 6.7; p<0.001). There was a trend towards a
lower 30-day PPM rate in patients with a shallower (<=5 mm) implant depth (23.9%
<=5 mm vs. 36.9% >5 mm depth from LCS; p=0.06). CONCLUSIONS: Careful attention to
valve sizing and implant depth may help to reduce the rate of PPM with the LOTUS
valve.
PMID- 28506943
TI - Do clinical data and human papilloma virus genotype influence spontaneous
regression in grade I cervical intraepithelial neoplasia?
AB - OBJECTIVE: To determine whether medical history, clinical examination and human
papilloma virus (HPV) genotype influence spontaneous regression in cervical
intraepithelial neoplasia grade I (CIN-I). MATERIAL AND METHODS: We
retrospectively evaluated 232 women who were histologically diagnosed as have CIN
I by means of Kaplan-Meier curves, the pattern of spontaneous regression
according to the medical history, clinical examination, and HPV genotype.
RESULTS: Spontaneous regression occurred in most patients and was influenced by
the presence of multiple HPV genotypes but not by the HPV genotype itself. In
addition, regression frequency was diminished when more than 50% of the cervix
surface was affected or when an abnormal cytology was present at the beginning of
follow-up. CONCLUSION: The frequency of regression in CIN-I is high, making long
term follow-up and conservative management advisable. Data from clinical
examination and HPV genotyping might help to anticipate which lesions will
regress.
PMID- 28506944
TI - Effect of sacrocolpopexy and retropubic sling on overactive bladder symptoms.
AB - OBJECTIVE: In this study, we aimed to evaluate the effect of sacrocolpopexy and
retropubic midurethral sling, or transvaginal tape (TVT) procedure, on overactive
bladder (OAB) symptoms. Our null hypothesis was that concomitant sacrocolpopexy
and TVT exacerbate OAB symptoms. MATERIAL AND METHODS: This is a prospective
cohort study. All subjects had apical/anterior prolapse and underwent robotic
assisted sacrocolpopexy and TVT, with or without concomitant hysterectomy. All
subjects completed a standardized one-year follow-up between 2009 and 2014. To
assess for OAB symptoms, we used the Urogenital Distress Inventory subscale
questions #15 and/or question #16. Reponses to these questions are based on a
five-point 0 to 4 Likert scale (0 represents a negative response or no symptoms,
and 4 represents the most problems). Any patient who answered 1 or higher on the
Likert scale, either on the frequency or urge incontinence question, was defined
as having OAB symptoms. RESULTS: Sixty-six subjects completed 12 months of
visits. Preoperatively, 54 patients (83%) had OAB symptoms, and postoperatively
29 patients (45%) had OAB symptoms (p<0.001). Patients with postoperative OAB had
a lower patient global impression of improvement (PGI-I) scores, PGI-I 5.8 with
OAB, and PGI-I 6.6 without OAB (p<0.003). CONCLUSION: We found that
sacrocolpopexy and concomitant retropubic midurethral sling does not contribute
to additive OAB symptoms, and symptoms actually resolved in 38% of women in our
cohort. The presence of postoperative OAB contributes to lower global impression
of improvement.
PMID- 28506945
TI - Urinary fistula-A continuing problem with changing trends.
AB - OBJECTIVE: Urinary fistula is a distressing complication after difficult vaginal
deliveries, obstetric, and gynecologic surgeries. The present study describes a
single center's experience in the management of urinary fistula at a tertiary
care hospital. It was performed to analyze the etiology of genitourinary fistula,
to assess the outcome after surgical repair, and to determine the changing trends
in the etiology and management of urinary fistula. MATERIAL AND METHODS: This
retrospective study was conducted over 5 years in the department of obstetrics
and gynecology, All India Institute of Medical Sciences, New Delhi. Twenty
patients who underwent surgical repair of urinary fistula were included in the
study and analyzed for their etiology, presentation, site, size, previous failed
repair, approach of surgical repair, and outcome. The findings of the present
study were compared with a previous study at our center to determine the changing
trends of urinary fistula. RESULTS: The mean age of the study population was
37.05+/-8.08 years. The majority (65%) of the fistulae occurred following
gynecologic surgeries, whereas 25% were due to obstructed labor, and 10% after
cesarean section for other indications. The vaginal approach was used in all
except one case of uterovesical fistula, which was repaired abdominally. The
outcome was successful in 85% of cases. The success rate was similar in primary
versus previous failed repair (p=0.270). CONCLUSION: The most common cause of
urinary fistula in the present study was gynecologic surgery. The vaginal
approach can be used even in cases with previous failed repairs with a high
success rate.
PMID- 28506947
TI - Comparison of bilateral transversus abdominis plane block and wound infiltration
with bupivacaine for postoperative analgesia after cesarean delivery.
AB - OBJECTIVE: The study aimed to compare efficacy, safety, pain intensity and
analgesic consumption in patients receiving either bilateral transversus
abdominis plane (TAP) block or wound infiltration with bupivacaine after cesarean
delivery (CD). MATERIAL AND METHODS: A total of 216 parturient women undergoing
CD under general anesthesia were randomly allocated into five groups: i) controls
(group 1), ii) TAP placebo (group 2), iii) TAP (group 3), iv) wound infiltration
placebo (group 4), and, v) wound infiltration (group 5). Pain intensity was
assessed using a visual analogue scale (VAS). Analgesic consumptions were
recorded by a blinded nurse at 6, 12, and 18 hours postoperatively. RESULTS: The
baseline characteristics of the five groups were similar in terms of age, history
of CD, and body mass indices (p>0.05). There were significant intergroup
differences in VAS scores between all groups at the zero time-point (p=0.03), at
the 6th hour (p=0.02), 12th hour (p=0.02), and at the 18th hour (p=0.02). Group 3
patients had lower pain scores and consumed less diclofenac than group 2 patients
only within 12 hours postoperatively whereas pain intensity and analgesic
consumption were not different between group 5 and group 4 patients. Group 5
patients received significantly less pethidine than group 4 and group 1 patients
(p<0.001). CONCLUSION: TAP block provided better pain relief and less analgesic
requirement than bupivacaine wound infiltration early after CD. Given the similar
amounts of diclofenac but lower amounts of pethidine administered in the wound
infiltration group, wound infiltration of bupivacaine seems promising in terms of
reducing opioid use after CD under general anesthesia, especially when TAP block
is not used.
PMID- 28506946
TI - Maternal mortality due to hypertensive disorders in pregnancy, childbirth, and
the puerperium between 2012 and 2015 in Turkey: A nation-based study.
AB - OBJECTIVE: To analyze maternal deaths in Turkey due to hypertensive disorders.
MATERIAL AND METHODS: In this retrospective study 812 maternal deaths were
analyzed. Maternal demographic features, presence of antenatal care, medical and
obstetric history, mode of delivery, and use emergency antihypertensive therapy
were recorded. The delay model for each case was investigated. RESULTS:
Hypertensive disorders accounted for 15.5% (n=126) out of all maternal mortality.
They were the third most frequent cause among all causes and the 2nd among direct
causes of maternal deaths. Sixty-one (48.4%) cases were in severe preeclampsia or
pre-existing hypertensive disorder with increased/superimposed proteinuria, 30.1%
were in eclampsia, 9.5% cases were diagnosed as hemolysis, elevated liver
enzymes, low platelet count syndrome, and 11.1% in pre-existing hypertension
complicating pregnancy, childbirth, and puerperium without increased or
superimposed proteinuria. The median age was 32 years, 37.3% women were >=35
years. All deaths except for 2 cases occurred during the postpartum period.
Twenty-three percent of deaths occurred in the first 48 hours postpartum, and
51.6% between 8-42 days. Intracranial hemorrhage was the major final cause of
death with a rate of 41.3%. With the exception of fifteen patients with
intracranial hemorrhage, emergency antihypertensive agents were not implemented
in optimal dose and/or duration. A first and/or third delay was identified in
36.5% of cases. CONCLUSION: Approximately one third of maternal death due to
hypertensive disorders could be prevented. The importance of acute
antihypertensive treatment should be emphasized because of most frequent cause of
death was intracranial hemorrhage.
PMID- 28506948
TI - Stage IIIC transitional cell carcinoma and serous carcinoma of the ovary have
similar outcomes when treated with platinum-based chemotherapy.
AB - OBJECTIVE: Previous studies reported better outcomes for transitional cell
carcinoma (TCC) of the ovary when compared with more common histologic types such
as serous epithelial ovarian cancers (EOCs). The aim of this study was to compare
the survival outcomes of platinum- based chemotherapy in patients with stage IIIC
TCCs and serous EOCs. MATERIAL AND METHODS: Clinicopathologic features and
survival data of patients with FIGO stage IIIC TCC and serous EOC who had
undergone primary surgery followed by six cycles of intravenous platinum/taxane
between 2007 and 2015 were retrieved from the database of Hacettepe University
Hospital. RESULTS: We identified 14 (10.9%) TCCs and 114 (89.1%) serous EOCs. The
median follow-up duration was 28 months (range, 3-101 months). Univariate
analysis revealed that the TCCs and serous EOCs had similar progression-free
survival (PFS) and overall survival (OS). Patients with residual disease less
than 1 cm had longer OS than patients with residual disease greater than 1 cm
(75.0 vs. 45.0 months, p=0.012). Cox regression analysis of all potential
prognostic factors showed that the only independent prognostic factor
significantly associated with OS was residual disease less than 1 cm [hazard
ratio=0.38; 95% confidence interval: (0.19-0.77); p=0.007]. CONCLUSION:
Surgically treated advanced stage TCCs did not have a significantly better
prognosis after platinum/taxane-based chemotherapy when compared with serous
EOCs. Residual tumor volume after primary surgery was the only independent
predictor of OS in patients with EOC. Our results demonstrate the significance of
achieving optimal cytoreduction in all histologic subtypes of EOC.
PMID- 28506949
TI - Frozen embryo transfer prevents the detrimental effect of high estrogen on
endometrium receptivity.
AB - OBJECTIVE: To investigate whether serum levels of estradiol affect reproductive
outcomes of normoresponder women undergoing fresh embryo transfer (ET) versus
frozen-thawed ET (FET). MATERIAL AND METHODS: Two hundred fifty-five
normoresponder women underwent fresh ET in their first or second in vitro
fertilization cycle. Ninety-two women with negative pregnacy test results
underwent FET. Clinical and ongoing pregnancy rates, implantation, and live birth
rates of women undergoing fresh ET versus FET were compared. RESULTS: One hundred
forty-seven (57.65%) out of the 255 normoresponder women receiving FET had
positive beta-human chorionic gonadotrophin (hCG) results. The remaining 108
women had negative beta-hCG results. The clinical pregnancy rates of the fresh ET
group were found as 55.69% (n=142). Ninety-two of the 108 women with failed
pregnancies underwent FET; 72.83% had positive beta-hCG results (n=67), and
70.65% had clinical pregnancy (n=65). Both biochemical and clinical pregnancy
rates of women undergoing FET increased significantly (p<0.012 and p<0.013,
respectively). Ongoing pregnancy (60.87% vs. 52.94%) and live birth rates (59.87%
vs. 48.63%) were similar in both fresh and FET groups. Serum E2 levels of women
who failed to conceive were significantly higher than those women did conceive.
Serum progesterone levels of women who conceived versus those that did not were
similar. CONCLUSION: The detrimental effect of high serum estradiol levels on
endometrial receptivity could be prevented by FET.
PMID- 28506950
TI - Fertility sparing approach as the standard of care in young patients with
immature teratomas.
AB - Immature teratomas are quite rare tumors arising in young women. They are usually
diagnosed in early stage and grade and have a good prognosis. In these young
patients, fertility-sparing management is suggested as the standard of care.
Bilateral immature teratoma is a rare condition with an incidence of 10%, with a
five-year survival rate of 80%. The majority of patients received fertility
sparing treatment followed by adjuvant chemotherapy in 78%. Older age, advanced
stage, and high grade are negative prognostic factors. The surgery-only, watch
and-wait approach was evaluated; however, after a median follow-up time of 42
months, 50% of patients experienced recurrence, but they were successfully
salvaged with chemotherapy. In a retrospective study, 12 out of 27 patients tried
to conceive, resulting in 10 pregnancies (8 after chemotherapy). We present a
narrative review of the current literature regarding the essential
multidisciplinary approach of such patients in order to achieve the best
oncologic and fertility-sparing outcome.
PMID- 28506951
TI - Pharmacokinetic, pharmacodynamic, and clinical aspects of ovulation induction
agents: A review of the literature.
AB - Controlled ovarian hyperstimulation is a key step for successful outcomes of
assisted reproductive technique cycle outcomes. Many medications are available,
which are commonly useed solely or in combination to achieve multiple follicular
development. Pharmacokinetic, pharmacodynamic, and clinical information of
ovulation induction drugs deserve to be elucidated for every individual patient
before commencing infertility treatment. New concepts and new treatment protocols
are introduced as ovulation physiology is understood by infertility specialists.
Increasing treatment success by minimizing aderse effects is a milestone of all
ovarian stimulation protocols that use these novel interventions. Achievement of
a satisfactory cycle outcome includes retrieval of sufficient oocytes, a single
clinical pregnancy, and avoidance of ovarian hyperstimulation syndrome. In this
review, we evaluate the current literature to determine the most reliable and
relevant information about the most used ovulation induction drugs.
PMID- 28506952
TI - Retrospective evaluation of pregnant women with celiac disease.
AB - OBJECTIVE: To show celiac disease (CD) and its poor pregnancy outcome
relationship, and to demonstrate the importance of a gluten-free diet together
with low-dose low-molecular-weight heparin (LMWH) and low-dose corticosteroid
(LDC) in the management of pregnancies with CD. MATERIAL AND METHODS: This study
consisted of 2 groups of patients. Six patients with CD (control group) on a
gluten-free diet were monitored during their first pregnancies within the
framework of antenatal care program and their pregnancy outcomes were compared
with eight poorly-treated pregnant patients with CD (study group) who were
referred from other medical institutions. LMWH (enoxaparine 1x2000 Anti-XA IU/0.2
mL/day), and LDC (methylprednisolone 1x4 mg p.o/day) were used in the control
group. Their obstetric histories and outcomes of their last pregnancies were
compared. The patients' obstetric risk levels were evaluated using the "Beksac
Obstetrics Index" (BOI). RESULTS: There were miscarriages in 50% of the study
group. There were also 50% and 75% preterm deliveries in the control and study
groups, respectively. The BOI of the study group was significantly worse than the
control group (1.31 vs. 0.31+/-0.21, p<0.01). There were no statistically
significant differences between age (24+/-4.7 vs 31.7+/-6 years, p=0.448),
gestational day of birth (259.3+/-8.5 vs 246.6+/-24.3), birthweight (2691+/-698
vs 2262+/-359 g, p=0.394), and cesarean section rates (p=0.118). CONCLUSION: CD
is a risk factor for adverse pregnancy outcome. Miscarriage and preterm labor are
critical complications in pregnancies complicated by CD. A gluten-free diet is
important in the treatment. LMWH and LDC seem to be helpful in the management of
pregnant women with CD.
PMID- 28506953
TI - What is your diagnosis?
PMID- 28506954
TI - EpxMedTracking: Feasibility Evaluation of an SMS-Based Medication Adherence
Tracking System in Community Practice.
AB - BACKGROUND: Medication adherence remains a difficult problem to both assess and
improve in patients. It is a multifactorial problem that goes beyond the commonly
cited reason of forgetfulness. To date, eHealth (also known as mHealth and
telehealth) interventions to improve medication adherence have largely been
successful in improving adherence. However, interventions to date have used time-
and cost-intensive strategies or focused solely on medication reminding, leaving
much room for improvement in using a modality as flexible as eHealth. OBJECTIVE:
Our objective was to develop and implement a fully automated short message
service (SMS)-based medication adherence system, EpxMedTracking, that reminds
patients to take their medications, explores reasons for missed doses, and alerts
providers to help address problems of medication adherence in real time. METHODS:
EpxMedTracking is a fully automated bidirectional SMS-based messaging system with
provider involvement that was developed and implemented through Epharmix, Inc.
Researchers analyzed 11 weeks of de-identified data from patients cared for by
multiple provider groups in routine community practice for feasibility and
functionality. Patients included were those in the care of a provider purchasing
the EpxMedTracking tool from Epharmix and were enrolled from a clinic by their
providers. The primary outcomes assessed were the rate of engagement with the
system, reasons for missing doses, and self-reported medication adherence.
RESULTS: Of the 25 patients studied over the 11 weeks, 3 never responded and
subsequently opted out or were deleted by their provider. No other patients opted
out or were deleted during the study period. Across the 11 weeks of the study
period, the overall weekly engagement rate was 85.9%. There were 109 total
reported missed doses including "I forgot" at 33 events (30.3%), "I felt better"
at 29 events (26.6%), "out of meds" at 20 events (18.4%), "I felt sick" at 19
events (17.4%), and "other" at 3 events (2.8%). We also noted an increase in self
reported medication adherence in patients using the EpxMedTracking system.
CONCLUSIONS: EpxMedTracking is an effective tool for tracking self-reported
medication adherence over time. It uniquely identifies actionable reasons for
missing doses for subsequent provider intervention in real time based on patient
feedback. Patients enrolled on EpxMedTracking also self-report higher rates of
medication adherence over time while on the system.
PMID- 28506955
TI - Text Messaging and Mobile Phone Apps as Interventions to Improve Adherence in
Adolescents With Chronic Health Conditions: A Systematic Review.
AB - BACKGROUND: The number of adolescents with chronic health conditions (CHCs)
continues to increase. Medication nonadherence is a global challenge among
adolescents across chronic conditions and is associated with poor health
outcomes. While there has been growing interest in the use of mHealth technology
to improve medication adherence among adolescents with CHCs, particularly text
messaging and mobile phone apps, there has been no prior systematic review of
their efficacy. OBJECTIVE: The purpose of this review was to systematically
evaluate the most recent evidence for the efficacy of text messaging and mobile
phone apps as interventions to promote medication adherence among adolescents
with CHCs. METHODS: PubMed, Embase, CENTRAL, PsycINFO, Web of Science, Google
Scholar, and additional databases were searched from 1995 until November 2015. An
additional hand search of related themes in the Journal of Medical Internet
Research was also conducted. The Preferred Reporting Results of Systematic
Reviews and Meta-Analyses guidelines were followed. Two reviewers independently
screened titles/abstracts, assessed full-text articles, extracted data from
included articles, and assessed their quality using Grades of Recommendation,
Assessment, Development, and Evaluation criteria. Included studies were described
in original research articles that targeted adherence in adolescents with CHCs
(12-24 years-old). RESULTS: Of the 1423 records examined, 15 met predefined
criteria: text messaging (n=12) and mobile phone apps (n=3). Most studies were
performed in the United States (11/15, 73%), were randomized-controlled trials
(8/15, 53%), had a sample size <50 (11/15, 73%), and included adherence self
report and/or biomarkers (9/15, 60%). Only four studies were designed based on a
theoretical framework. Approaches for text messaging and mobile phone app
interventions varied across studies. Seven articles (7/15, 47%) reported
significant improvement in adherence with moderate to large standardized mean
differences. Most of the included studies were of low or moderate quality.
Studies varied in sample size, methods of adherence assessment, and definition of
adherence, which prohibited performing a meta-analysis. CONCLUSIONS: The use of
text messaging and mobile phone app interventions to improve medication adherence
among adolescents with CHCs has shown promising feasibility and acceptability,
and there is modest evidence to support the efficacy of these interventions.
Further evaluation of short- and long-term efficacy and cost-effectiveness of
these interventions is warranted given the early and evolving state of the
science.
PMID- 28506956
TI - Web-Based Cognitive Behavior Therapy for Depression in People With Diabetes
Mellitus: A Randomized Controlled Trial.
AB - BACKGROUND: Depression is twice as common in diabetes mellitus (DM) as the
general population and is associated with adverse health outcomes, but access to
evidence-based therapies such as cognitive behavioral therapy (CBT) is limited in
routine diabetes care. Past research has shown that generic Internet-based
cognitive behavioral therapy (iCBT) is an effective treatment for depression in
the general population, but it has never been evaluated in people with comorbid
depression and DM. OBJECTIVE: The aim of our study was to examine the efficacy of
a generic 6-lesson iCBT delivered over 10 weeks in people with major depressive
disorder (MDD) and DM. METHODS: Participants with comorbid MDD and DM (type 1 or
2) were recruited online and randomized to an iCBT program with therapist support
provided by phone and email (n=42) or a treatment as usual (TAU, n=49) control
group. Outcomes were assessed through Web-based self-report questionnaires and
the trial was Web-based with no face-to-face components. Primary outcomes were
self-reported depression (patient health questionnaire-9, PHQ-9), diabetes
related distress (problem areas in diabetes, PAID), and self-reported glycemic
control (hemoglobin A1c, HbA1c). Secondary outcomes were general distress
(Kessler 10-item psychological distress scale, K-10) and disability (short form
12-item, SF-12), generalized anxiety (generalized anxiety disorder 7-item, GAD
7), and somatization (PHQ-15). The iCBT group was assessed at 3 months. RESULTS:
A total of 27 participants (66%; 27/41) completed the iCBT program. Analyses
indicated between-group superiority of iCBT over TAU at posttreatment on PHQ-9
(g=0.78), PAID (g=0.80), K-10 (g=1.06), GAD-7 (g=0.72), and SF-12 mental well
being scores (g=0.66), but no significant differences in self-reported HbA1c
levels (g=0.14), SF-12 physical well-being, or PHQ-15 scores (g=0.03-0.21). Gains
were maintained at 3-month follow-up in the iCBT group, and the 87% (27/31) of
iCBT participants who were interviewed no longer met criteria for MDD. Clinically
significant change following iCBT on PHQ-9 scores was 51% (21/41) versus 18%
(9/49) in TAU. CONCLUSIONS: iCBT for depression is an efficacious, accessible
treatment option for people with diabetes. Future studies should explore whether
tailoring of iCBT programs improves acceptability and adherence, and evaluate the
long-term outcomes following iCBT. TRIAL REGISTRATION: Australian and New Zealand
Clinical Trials Registry (ACTRN): 12613001198718;
https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365208&isReview=
rue (Archived by WebCite at http://www.webcitation.org/6qCR8Fi9V).
PMID- 28506957
TI - Computer Administered Safety Planning for Individuals at Risk for Suicide:
Development and Usability Testing.
AB - BACKGROUND: Safety planning is a brief intervention that has become an accepted
practice in many clinical settings to help prevent suicide. Even though it is
quick compared to other approaches, it frequently requires 20 min or more to
complete, which can impede adoption. A self-administered, Web-based safety
planning application could potentially reduce clinician time, help promote
standardization and quality, and provide enhanced ability to share the created
plan. OBJECTIVE: The aim of this study was to design, build, and test the
usability of a Web-based, self-administered safety planning application. METHODS:
We employed a user-centered software design strategy led by a multidisciplinary
team. The application was tested for usability with a target sample of suicidal
patients. Detailed observations, structured usability ratings, and Think Aloud
procedures were used. Suicidal ideation intensity and perceived ability to cope
were assessed pre-post engagement with the Web application. RESULTS: A total of
30 participants were enrolled. Usability ratings were generally strong, and all
patients successfully built a safety plan. However, the completeness of the
safety plan varied. The mean number of steps completed was 5.5 (SD 0.9) out of 6,
with 90% (27/30) of participants completing at least 5 steps and 67% (20/30)
completing all 6 steps. Some safety planning steps were viewed as inapplicable to
some individuals. Some confusion in instructions led to modifications to improve
understandability of each step. Ratings of suicide intensity after completion of
the application were significantly lower than preratings, pre: mean 5.11 (SD 2.9)
versus post: mean 4.46 (SD 3.0), t27=2.49, P=.02. Ratings of ability to cope with
suicidal thoughts after completion of the application were higher than
preratings, with the difference approaching statistical significance, pre: mean
5.93 (SD 2.9), post: mean 6.64 (SD 2.4), t27=-2.03, P=.05. CONCLUSIONS: We have
taken the first step toward identifying the components needed to maximize
usability of a self-administered, Web-based safety planning application. Results
support initial consideration of the application as an adjunct to clinical
contact. This allows for the clinician or other personnel to provide
clarification, when needed, to help the patient build the plan, and to help
review and revise the draft.
PMID- 28506958
TI - Enhancing Comparative Effectiveness Research With Automated Pediatric Pneumonia
Detection in a Multi-Institutional Clinical Repository: A PHIS+ Pilot Study.
AB - BACKGROUND: Community-acquired pneumonia is a leading cause of pediatric
morbidity. Administrative data are often used to conduct comparative
effectiveness research (CER) with sufficient sample sizes to enhance detection of
important outcomes. However, such studies are prone to misclassification errors
because of the variable accuracy of discharge diagnosis codes. OBJECTIVE: The aim
of this study was to develop an automated, scalable, and accurate method to
determine the presence or absence of pneumonia in children using chest imaging
reports. METHODS: The multi-institutional PHIS+ clinical repository was developed
to support pediatric CER by expanding an administrative database of children's
hospitals with detailed clinical data. To develop a scalable approach to find
patients with bacterial pneumonia more accurately, we developed a Natural
Language Processing (NLP) application to extract relevant information from chest
diagnostic imaging reports. Domain experts established a reference standard by
manually annotating 282 reports to train and then test the NLP application.
Findings of pleural effusion, pulmonary infiltrate, and pneumonia were
automatically extracted from the reports and then used to automatically classify
whether a report was consistent with bacterial pneumonia. RESULTS: Compared with
the annotated diagnostic imaging reports reference standard, the most accurate
implementation of machine learning algorithms in our NLP application allowed
extracting relevant findings with a sensitivity of .939 and a positive predictive
value of .925. It allowed classifying reports with a sensitivity of .71, a
positive predictive value of .86, and a specificity of .962. When compared with
each of the domain experts manually annotating these reports, the NLP application
allowed for significantly higher sensitivity (.71 vs .527) and similar positive
predictive value and specificity . CONCLUSIONS: NLP-based pneumonia information
extraction of pediatric diagnostic imaging reports performed better than domain
experts in this pilot study. NLP is an efficient method to extract information
from a large collection of imaging reports to facilitate CER.
PMID- 28506959
TI - Health-Related Internet Use in People With Cancer: Results From a Cross-Sectional
Study in Two Outpatient Clinics in Sweden.
AB - BACKGROUND: The access to various forms of support during the disease trajectory
is crucial for people with cancer. The provision and use of Internet health
services is increasing, and it is important to further investigate the
preferences and demographical characteristics of its users. Investigating the
uptake and perceived value of Internet health services is a prerequisite to be
able to meet the needs in the targeted group. OBJECTIVE: The objective of this
study was to investigate health-related Internet use among people with cancer.
METHODS: The health online support questionnaire (HOSQ), examining the incentives
for health-related Internet support use, was administered in two Swedish
outpatient hospital clinics. Of the 350 copies of the questionnaire handed out,
285 (81.4%) were returned, answered by persons with cancer who had completed
treatment or were under active surveillance or another medical treatment.
RESULTS: A total of 215 (76.2%, 215/282) participants reported Internet use since
being diagnosed with cancer. Internet-users were younger (P<.001), more likely to
have a partner (P=.03), and had a higher level of education than nonusers
(P<.001). The most common health-related activity on the Internet was searching
for information (77.2%, 166/215), and users searched significantly more
immediately after diagnosis compared with later on (P<.001). Use of My Healthcare
Contacts was considered the most valuable Internet activity. Having a university
degree (P ?.001) and being younger in age (P=.01) were associated with a
significantly higher frequency of health- related Internet use. CONCLUSIONS:
People with cancer turn to the Internet for informational support that enables
them to influence their care and to stay in touch with friends and relatives.
Demographical differences regarding the uptake of Web-based support remains. This
indicates a need for research on how to bridge this digital gap. By learning more
about the use of health-related support on the Web among people with cancer,
adequate support can be offered and potential strain reduced.
PMID- 28506961
TI - Gene Team in Blood Pressure Genetics.
PMID- 28506960
TI - Familial Analysis of Epistatic and Sex-Dependent Association of Genes of the
Renin-Angiotensin-Aldosterone System and Blood Pressure.
AB - BACKGROUND: Renin-angiotensin-aldosterone system genes have been inconsistently
associated with blood pressure, possibly because of unrecognized influences of
sex-dependent genetic effects or gene-gene interactions (epistasis). METHODS AND
RESULTS: We tested association of systolic blood pressure with single-nucleotide
polymorphisms (SNPs) at renin (REN), angiotensinogen (AGT), angiotensin
converting enzyme (ACE), angiotensin II type 1 receptor (AGTR1), and aldosterone
synthase (CYP11B2), including sex-SNP or SNP-SNP interactions. Eighty-eight
tagSNPs were tested in 2872 white individuals in 809 pedigrees from the Victorian
Family Heart Study using variance components models. Three SNPs (rs8075924 and
rs4277404 at ACE and rs12721297 at AGTR1) were individually associated with lower
systolic blood pressure with significant (P<0.00076) effect sizes ~1.7 to 2.5 mm
Hg. Sex-specific associations were seen for 3 SNPs in men (rs2468523 and
rs2478544 at AGT and rs11658531 at ACE) and 1 SNP in women (rs12451328 at ACE).
SNP-SNP interaction was suggested (P<0.005) for 14 SNP pairs, none of which had
shown individual association with systolic blood pressure. Four SNP pairs were at
the same gene (2 for REN, 1 for AGT, and 1 for AGTR1). The SNP rs3097 at CYP11B2
was represented in 5 separate pairs. CONCLUSIONS: SNPs at key renin-angiotensin
aldosterone system genes associate with systolic blood pressure individually in
both sexes, individually in one sex only and only when combined with another SNP.
Analyses that incorporate sex-dependent and epistatic effects could reconcile
past inconsistencies and account for some of the missing heritability of blood
pressure and are generally relevant to SNP association studies for any phenotype.
PMID- 28506963
TI - Aspirin and Pancreatic Cancer-Response.
PMID- 28506964
TI - Population-Based Precision Cancer Screening-Letter.
PMID- 28506962
TI - Pair Feeding, but Not Insulin, Phloridzin, or Rosiglitazone Treatment, Curtails
Markers of beta-Cell Dedifferentiation in db/db Mice.
AB - beta-Cell failure is a hallmark of type 2 diabetes. Among several cellular
biological mechanisms of cellular dysfunction, we and others have recently
proposed that dedifferentiation of beta-cells can explain the slowly progressive
onset and partial reversibility of beta-cell failure. Accordingly, we provided
evidence of such processes in humans and experimental animal models of insulin
resistant diabetes. In this study, we asked whether beta-cell dedifferentiation
can be prevented with diet or pharmacological treatment of diabetes. db/db mice,
a widely used model of insulin-resistant diabetes and obesity, were either pair
fed or treated with the Sglt inhibitor phloridzin, the insulin-sensitizer
rosiglitazone, or insulin. All treatments were equally efficacious in reducing
plasma glucose levels. Pair feeding and phloridzin also resulted in significant
weight loss. However, pair feeding among the four treatments resulted in a
reduction of beta-cell dedifferentiation, as assessed by Foxo1 and Aldh1a3
immunohistochemistry. The effect of diet to partly restore beta-cell function is
consistent with data in human diabetes and provides another potential mechanism
by which lifestyle changes act as an effective intervention against diabetes
progression.
PMID- 28506966
TI - Metformin, Diabetes, and Survival among U.S. Veterans with Colorectal Cancer
Letter.
PMID- 28506967
TI - Aspirin and Pancreatic Cancer-Letter.
PMID- 28506965
TI - Explaining the Obesity Paradox: The Association between Body Composition and
Colorectal Cancer Survival (C-SCANS Study).
AB - Background: Body composition may partially explain the U-shaped association
between body mass index (BMI) and colorectal cancer survival.Methods: Muscle and
adiposity at colorectal cancer diagnosis and survival were examined in a
retrospective cohort using Kaplan-Meier curves, multivariable Cox regression, and
restricted cubic splines in 3,262 early-stage (I-III) male (50%) and female (50%)
patients. Sarcopenia was defined using optimal stratification and sex- and BMI
specific cut points. High adiposity was defined as the highest tertile of sex
specific total adipose tissue (TAT). Primary outcomes were overall mortality and
colorectal cancer-specific mortality (CRCsM).Results: Slightly over 42% patients
were sarcopenic. During 5.8 years of follow-up, 788 deaths occurred, including
433 from colorectal cancer. Sarcopenic patients had a 27% [HR, 1.27; 95%
confidence interval (CI), 1.09-1.48] higher risk of overall mortality than those
who were not sarcopenic. Females with both low muscle and high adiposity had a
64% higher risk of overall mortality (HR, 1.64; 95% CI, 1.05-2.57) than females
with adequate muscle and lower adiposity. The lowest risk of overall mortality
was seen in patients with a BMI between 25 and <30 kg/m2, a range associated with
the greatest number of patients (58.6%) who were not at increased risk of overall
mortality due to either low muscle or high adiposity.Conclusions: Sarcopenia is
prevalent among patients with non-metastatic colorectal cancer, and should, along
with adiposity be a standard oncological marker.Impact: Our findings suggest a
biologic explanation for the obesity paradox in colorectal cancer and refute the
notion that the association between overweight and lower mortality is due solely
to methodologic biases. Cancer Epidemiol Biomarkers Prev; 26(7); 1008-15. (c)2017
AACR.
PMID- 28506968
TI - The Obesity Paradox in Cancer-Moving beyond BMI-Response.
PMID- 28506969
TI - The Obesity Paradox and Cancer-Letter.
PMID- 28506970
TI - Metformin, Diabetes, and Survival among U.S. Veterans with Colorectal Cancer
Response.
PMID- 28506972
TI - Career and research outcomes of the physician-scientist training program at the
University of Calgary: a retrospective cohort study.
AB - BACKGROUND: Physician-scientists are integral to medical research, with medical
programs throughout Canada invested in training hybrid physician-scientists. Few
data exist as to whether these programs are generating the diversity, gender
equity and numbers of trainees essential for the future of medical research and
teaching. We aimed to identify factors that contribute to research productivity,
diversity and retention of individuals as physician-scientists. METHODS: We
completed a retrospective cohort study, for the period 1973 to 2015, of the
University of Calgary Leaders in Medicine Program in Calgary, Alberta.
Participants were coregistered in graduate (master's or PhD) and medical degree
programs. Primary outcomes included number of publications and the eventual
career paths of graduates, with individuals characterized as physicians or
physician-scientists on the basis of these metrics. RESULTS: Of the 307
individuals who were coregistered in or had completed a joint graduate and
medical degree, 125 (40.7%) were PhD students/graduates, and 182 (59.3%) were
master's trainees/graduates. While in the joint program, male PhD students
consistently published more frequently than female PhD students. There was no
significant difference in publication records between male and female master's
students. Of the 172 individuals who were 5 years or more beyond graduation, 47
(27.3%) were classified as physician-scientists; these individuals consisted of
28 (40.6%) of the 69 PhD graduates and 19 (18.4%) of the 103 master's graduates.
INTERPRETATION: Overall, our study shows that graduates receiving both clinical
and research training, through master's or PhD programs, continue to be involved
in research in their subsequent careers.
PMID- 28506974
TI - Assessment of reimbursement in a community hospital-based pharmacist-managed
outpatient transition clinic.
AB - PURPOSE: The assessment of reimbursement for and time spent on patient visits in
a newly implemented, outpatient pharmacist-managed transition clinic (TC) was
studied. METHODS: A retrospective chart review was conducted on clinic visits
that occurred during January 1 to December 31, 2015. Patients who had at least
one TC visit during the study period were included. Any visit with no response
from insurance by March 31, 2016, was excluded. Services provided by the TC were
billed using a facility fee billing model. The following data were collected:
number of visits, time length of individual visits, billed amount, level of
service, type of insurance, and amount reimbursed (from primary insurance,
secondary insurance, and total amount). Data were analyzed using descriptive
statistics. RESULTS: One hundred eight patients were eligible for inclusion in
the study, with a total of 306 eligible visits. Each patient had a mean of 2.82
visits. The mean +/- S.D. time spent per visit was 55 minutes. Visits were billed
at level 2 (2%), level 3 (36%), and level 4 (62%). Two hundred seventy-two visits
(89%) were partially or completely reimbursed by insurance, whereas 34 visits
(11%) provided no reimbursement. The mean +/- S.D. reimbursement was $99 +/-
$51.88 per visit. CONCLUSION: A pharmacist-managed TC service based in a
community hospital achieved a positive return on investment through insurer
reimbursement over a 12-month period.
PMID- 28506975
TI - National survey of comprehensive pharmacy services provided in cancer clinical
trials.
AB - PURPOSE: Pharmacy services provided in clinical trials at National Cancer
Institute (NCI)-designated centers were assessed. METHODS: This was a cross
sectional survey of 61 NCI-designated cancer centers. Directors of pharmacy were
contacted and data were collected electronically via Qualtrics over 2 months.
Trial participants were asked to estimate the frequency that their sites
performed 26 services and the perceived importance of these services. Services
were examined with respect to the difference between their reported performance
and their reported importance. Eight of the 26 services showed a difference of at
least 40% between the proportion of respondents performing the activities "often"
or "almost always" and the proportion considering them "important" or "very
important." Demographic information was collected, as well as perceived barriers.
RESULTS: Survey response rate was 59% (36 out of 61). The majority of services
for clinical trials (19 out of 26) were viewed as important for pharmacists to
perform; however, less than half (10 out of 26) were performed more than 50% of
the time. Eight services had a gap of more than 40% when comparing the importance
versus extent of implementation. Some of the largest gaps were reported in
investigator-initiated trials development, medication reconciliation, therapeutic
drug monitoring, and oral chemotherapy adherence assessment. Future studies can
assist with cost justification by demonstrating the regulatory, safety, and
financial benefits of pharmacist involvement in cancer trials. CONCLUSION: A
survey of pharmacy directors at cancer centers revealed gaps between what
respondents considered important pharmacist services in the provision of cancer
clinical trials and the actual performance of those services in their
institution.
PMID- 28506976
TI - Implementation of postdischarge follow-up telephone calls at a comprehensive
cancer center.
AB - PURPOSE: The development and implementation of a pharmacy-driven, postdischarge
follow-up telephone call program to assess medication adherence, provide
education, and address medication-related concerns are discussed. SUMMARY: Many
readmissions are avoidable through effective discharge planning and patient
follow-up after hospitalization. However, there is limited information on how to
effectuate this process. To address this barrier, a team consisting of a clinical
pharmacy specialist, a clinical pharmacy manager, a postgraduate year 1 pharmacy
resident, and an education specialist at The University of Texas MD Anderson
Cancer Center collaborated to create a postdischarge telephone call program
within a transitions-of-care (TOC) pilot program. Various education and training
materials were created to ensure trainees were competent. As of February 2016, 23
outpatient pharmacists and students have completed training, earning a median
pretest and posttest score of 6 and 9, respectively, out of 10. There have been
206 calls completed; 150 patients (73%) were successfully reached, and 20
patients (9%) declined the telephone call. Medication adherence assessed during
the telephone follow-up identified that 134 patients (89%) received their new
medications within 72 hours, and 87 patients (58%) were recognized as having one
or more discrepancies. CONCLUSION: Developing a TOC program similar to this pilot
program requires several resources including time, collaboration, and support
from the management team. Pharmacy is well positioned to complete an accurate
medication review and conduct postdischarge telephone calls to address medication
related issues. By providing these services, patients will receive continuity of
care and positively impact emergency room visitation rates and hospital
readmission rates.
PMID- 28506971
TI - Protein-Truncating Variants at the Cholesteryl Ester Transfer Protein Gene and
Risk for Coronary Heart Disease.
AB - RATIONALE: Therapies that inhibit CETP (cholesteryl ester transfer protein) have
failed to demonstrate a reduction in risk for coronary heart disease (CHD). Human
DNA sequence variants that truncate the CETP gene may provide insight into the
efficacy of CETP inhibition. OBJECTIVE: To test whether protein-truncating
variants (PTVs) at the CETP gene were associated with plasma lipid levels and
CHD. METHODS AND RESULTS: We sequenced the exons of the CETP gene in 58 469
participants from 12 case-control studies (18 817 CHD cases, 39 652 CHD-free
controls). We defined PTV as those that lead to a premature stop, disrupt
canonical splice sites, or lead to insertions/deletions that shift frame. We also
genotyped 1 Japanese-specific PTV in 27561 participants from 3 case-control
studies (14 286 CHD cases, 13 275 CHD-free controls). We tested association of
CETP PTV carrier status with both plasma lipids and CHD. Among 58 469
participants with CETP gene-sequencing data available, average age was 51.5 years
and 43% were women; 1 in 975 participants carried a PTV at the CETP gene.
Compared with noncarriers, carriers of PTV at CETP had higher high-density
lipoprotein cholesterol (effect size, 22.6 mg/dL; 95% confidence interval, 18-27;
P<1.0*10-4), lower low-density lipoprotein cholesterol (-12.2 mg/dL; 95%
confidence interval, -23 to -0.98; P=0.033), and lower triglycerides (-6.3%; 95%
confidence interval, -12 to -0.22; P=0.043). CETP PTV carrier status was
associated with reduced risk for CHD (summary odds ratio, 0.70; 95% confidence
interval, 0.54-0.90; P=5.1*10-3). CONCLUSIONS: Compared with noncarriers,
carriers of PTV at CETP displayed higher high-density lipoprotein cholesterol,
lower low-density lipoprotein cholesterol, lower triglycerides, and lower risk
for CHD.
PMID- 28506977
TI - Development of a medication review service for patients with enteral tubes in a
community teaching hospital.
AB - PURPOSE: The results of a study to develop a hospital-wide medication review
service for patients with enteral tubes to improve patient safety are presented.
SUMMARY: Inappropriate enteral administration of medications can result in
occluded tubes, altered clinical response, and an increase in adverse effects. At
Saint Barnabas Medical Center, a 600-bed community teaching hospital located in
Livingston, New Jersey, a medication review service for patients with an enteral
tube was developed. A phased approach was used. In phase 1, a retrospective chart
review revealed that 43% of our patients with enteral tubes received at least one
medication that should not be crushed. In phase 2, we identified formulary
medications that should not be crushed based on guidance from the Institute for
Safe Medication Practices. We added a "do not crush" warning to the identified
medications in our electronic medication administration record and automated
medication dispensing system. In phase 3, we created an automatic substitution
list of medications. Phase 4 involved the development of the program in our
health information technology platform. An electronic task list alerted
pharmacists about patients with enteral tubes who required medication review and
potential medication substitutions, as well as patients with newly removed
enteral tubes who can be placed back on their original medications. In phase 5,
we provided education to prescribers, nurses, and pharmacists. CONCLUSION: A
hospital-wide medication review service for patients with enteral tubes at our
community teaching medical center was developed.
PMID- 28506916
TI - 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and
surgical ablation of atrial fibrillation.
PMID- 28506978
TI - Addition of Blood Pressure and Weight Transmissions to Standard Remote Monitoring
of Implantable Defibrillators and its Association with Mortality and
Rehospitalization.
AB - BACKGROUND: Among patients with implantable defibrillators (ICD), use of remote
patient monitoring (RPM) is associated with lower risk of death and
rehospitalization. Standard ICD RPM can be supplemented with weight and blood
pressure data. It is not known whether standard RPM plus routine weight and blood
pressure transmission (RPM+) is associated with better outcomes. METHODS AND
RESULTS: RPM+ patients (n=4106) were compared with patients who only transmitted
standard ICD RPM data (n=14 183). Logistic regression models identified patient,
physician, and hospital characteristics associated with RPM+ utilization.
Mortality and rehospitalization were examined using landmark analyses at 180 days
after ICD implant in Medicare fee-for-service patients. In these analyses, we
examined the independent association between RPM+ utilization and times to events
up to 3 years after device implantation with Cox regression models. We further
examined whether the association between RPM+ and outcomes varied by frequency or
type of transmissions. Determinants of RPM+ utilization included impaired
ejection fraction, cardiac resynchronization therapy, and institutional practice.
The risk of mortality of RPM+ patients was similar to standard ICD RPM patients
(hazard ratio, 1.06; 95% confidence interval, 0.94-1.19; P=0.34). RPM+ patients
also had similar risks of all-cause hospitalization (subdistribution hazard
ratio, 1.03; 95% confidence interval, 0.94-1.14; P=0.52), cardiovascular
hospitalization (subdistribution hazard ratio, 0.92; 95% confidence interval,
0.83-1.02; P=0.15), or heart failure hospitalizations (subdistribution hazard
ratio, 0.90; 95% confidence interval, 0.78-1.05; P=0.18). RPM+ transmission
frequency was not associated with outcomes. CONCLUSIONS: In patients using
standard ICD RPM, the added transmission of weight and blood pressure data was
not associated with improved outcomes.
PMID- 28506979
TI - Impact of Ezetimibe on the Rate of Cardiovascular-Related Hospitalizations and
Associated Costs Among Patients With a Recent Acute Coronary Syndrome: Results
From the IMPROVE-IT Trial (Improved Reduction of Outcomes: Vytorin Efficacy
International Trial).
AB - BACKGROUND: Ezetimibe, when added to simvastatin therapy, reduces cardiovascular
events after recent acute coronary syndrome. However, the impact of ezetimibe on
cardiovascular-related hospitalizations and associated costs is unknown. METHODS
AND RESULTS: We used patient-level data from the IMPROVE-IT (Improved Reduction
of Outcomes: Vytorin Efficacy International Trial) to examine the impact of
simvastatin-ezetimibe versus simvastatin-placebo on cardiovascular-related
hospitalizations and related costs (excluding drug costs) over 7 years follow-up.
Medicare Severity-Diagnosis Related Groups were assigned to all cardiovascular
hospitalizations. Hospital costs were estimated using Medicare reimbursement
rates for 2013. Associated physician costs were estimated as a percentage of
hospital costs. The impact of treatment assignment on hospitalization rates and
costs was estimated using Poisson and linear regression, respectively. There was
a significantly lower cardiovascular hospitalization rate with ezetimibe compared
with placebo (risk ratio, 0.95; 95% confidence interval, 0.90-0.99; P=0.031),
mainly attributable to fewer hospitalizations for percutaneous coronary
intervention, angina, and stroke. Consequently, cardiovascular-related
hospitalization costs over 7 years were $453 per patient lower with ezetimibe
(95% confidence interval, -$38 to -$869; P=0.030). Although all prespecified
subgroups had lower cost with ezetimibe therapy, patients with diabetes mellitus,
patients aged >=75 years, and patients at higher predicted risk for recurrent
ischemic events had even greater cost offsets. CONCLUSIONS: Addition of ezetimibe
to statin therapy in patients with a recent acute coronary syndrome leads to
reductions in cardiovascular-related hospitalizations and associated costs, with
the greatest cost offsets in high-risk patients. These cost reductions may
completely offset the cost of the drug once ezetimibe becomes generic, and may
lead to cost savings from the perspective of the healthcare system, if treatment
with ezetimibe is targeted to high-risk patients. CLINICAL TRIAL REGISTRATION:
URL: https://www.clinicaltrials.gov. Unique Identifier: NCT00202878.
PMID- 28506982
TI - Social Risk Factors and Performance Under Medicare's Value-Based Purchasing
Programs.
PMID- 28506983
TI - Riskier Business: Atrial Fibrillation Stroke Prevention in the CHA2DS2-VASc Era.
PMID- 28506984
TI - Even on a Large Scale, Weight May Not Matter.
PMID- 28506981
TI - Contemporary Trends in Oral Anticoagulant Prescription in Atrial Fibrillation
Patients at Low to Moderate Risk of Stroke After Guideline-Recommended Change in
Use of the CHADS2 to the CHA2DS2-VASc Score for Thromboembolic Risk Assessment:
Analysis From the National Cardiovascular Data Registry's Outpatient Practice
Innovation and Clinical Excellence Atrial Fibrillation Registry.
AB - BACKGROUND: Use of the CHA2DS2-VASc score instead of the CHADS2 score for
thromboembolic risk stratification and initiation of oral anticoagulation (OAC)
was recommended in the 2014 American Heart Association/American College of
Cardiology/Heart Rhythm Society atrial fibrillation (AF) guidelines. We sought to
define the proportion of patients with AF qualifying for and receiving OAC in
contemporary practice by applying the CHA2DS2-VASc score to patients with a low
CHADS2 score. METHODS AND RESULTS: Among patients with AF enrolled in the
American College of Cardiology National Cardiovascular Data Registry's outpatient
Practice Innovation and Clinical Excellence registry (2008-2014) CHADS2 score of
0 or 1, we calculated the impact of adoption of the CHA2DS2-VASc score on the
proportion of patients with an indication for OAC. We examined trends in
prescription of OAC overall, direct OAC (dabigatran/rivaroxaban/apixaban), and
multivariable associations between clinical characteristics and OAC use. Of 346
068 patients with AF aged 65+/-12 years, 61% were men and 65% were white. In
total, 24% of those with CHADS2=0 and 81% of those with a CHADS2=1 were
reclassified as having a definite indication for OAC (CHA2DS2-VASc score >=2).
OAC use increased from 37% to 48% during the study period, and direct OAC use
increased from 5% to 30%. Increasing CHA2DS2-VASc score (odds ratio, 2.07; 95%
confidence interval, 1.97-2.19 for score of 4 versus 0) and rhythm control
strategy (odds ratio, 1.34; 95% confidence interval, 1.30-1.39) were associated
with increased OAC use. CONCLUSIONS: Adoption of the CHA2DS2-VASc score
reclassifies 64.5% of patients with AF with low CHADS2 scores into a class I
indication for OAC prescription. Overall OAC prescription increased between 2011
and 2014.
PMID- 28506980
TI - Sex Differences in Trajectories of Risk After Rehospitalization for Heart
Failure, Acute Myocardial Infarction, or Pneumonia.
AB - BACKGROUND: Women have an increased risk of rehospitalization in the immediate
postdischarge period; however, few studies have determined how readmission risk
dynamically changes on a day-to-day basis over the full year after
hospitalization by sex and how these differences compare with the risk for
mortality. METHODS AND RESULTS: We identified >3 000 000 hospitalizations of
patients with a principal discharge diagnosis of heart failure, acute myocardial
infarction, or pneumonia and estimated sex differences in the daily risk of
rehospitalization/death 1 year after discharge from a population of Medicare fee
for-service beneficiaries aged 65 years and older. We calculated the (1) time
required for adjusted rehospitalization/mortality risks to decline 50% from
maximum values after discharge, (2) time required for the adjusted readmission
risk to approach plateau periods of minimal day-to-day change, and (3) extent to
which adjusted risks are greater among recently hospitalized patients versus
Medicare patients. We identified 1 392 289, 530 771, and 1 125 231
hospitalizations for heart failure, acute myocardial infarction, and pneumonia,
respectively. The adjusted daily risk of rehospitalization varied by admitting
condition (hazard rate ratio for women versus men, 1.10 for acute myocardial
infarction; hazard rate ratio, 1.04 for heart failure; and hazard rate ratio,
0.98 for pneumonia). However, for all conditions, the adjusted daily risk of
death was higher among men versus women (hazard rate ratio women versus with men,
<1). For both sexes, there was a similar timing of peak daily risk, half daily
risk, and reaching plateau. CONCLUSIONS: Although the association of sex with
daily risk of rehospitalization varies across conditions, women are at highest
risk after discharge for acute myocardial infarction. Future studies should focus
on understanding the determinants of sex differences in rehospitalization risk
among conditions.
PMID- 28506985
TI - Histone acetyltransferase KAT8 is essential for mouse oocyte development by
regulating reactive oxygen species levels.
AB - Proper oocyte development is crucial for female fertility and requires timely and
accurate control of gene expression. K (lysine) acetyltransferase 8 (KAT8), an
important component of the X chromosome dosage compensation system in Drosophila,
regulates gene activity by acetylating histone H4 preferentially at lysine 16. To
explore the function of KAT8 during mouse oocyte development, we crossed
Kat8flox/flox mice with Gdf9-Cre mice to specifically delete Kat8 in oocytes.
Oocyte Kat8 deletion resulted in female infertility, with follicle development
failure in the secondary and preantral follicle stages. RNA-seq analysis revealed
that Kat8 deficiency in oocytes results in significant downregulation of
antioxidant genes, with a consequent increase in reactive oxygen species.
Intraperitoneal injection of the antioxidant N-acetylcysteine rescued defective
follicle and oocyte development resulting from Kat8 deficiency. Chromatin
immunoprecipitation assays indicated that KAT8 regulates antioxidant gene
expression by direct binding to promoter regions. Taken together, our findings
demonstrate that KAT8 is essential for female fertility by regulating antioxidant
gene expression and identify KAT8 as the first histone acetyltransferase with an
essential function in oogenesis.
PMID- 28506986
TI - SoxNeuro and Shavenbaby act cooperatively to shape denticles in the embryonic
epidermis of Drosophila.
AB - During development, extracellular signals are integrated by cells to induce the
transcriptional circuitry that controls morphogenesis. In the fly epidermis,
Wingless (Wg)/Wnt signaling directs cells to produce either a distinctly shaped
denticle or no denticle, resulting in a segmental pattern of denticle belts
separated by smooth, or 'naked', cuticle. Naked cuticle results from Wg
repression of shavenbaby (svb), which encodes a transcription factor required for
denticle construction. We have discovered that although the svb promoter responds
differentially to altered Wg levels, Svb alone cannot produce the morphological
diversity of denticles found in wild-type belts. Instead, a second Wg-responsive
transcription factor, SoxNeuro (SoxN), cooperates with Svb to shape the
denticles. Co-expressing ectopic SoxN with svb rescued diverse denticle
morphologies. Conversely, removing SoxN activity eliminated the residual
denticles found in svb mutant embryos. Furthermore, several known Svb target
genes are also activated by SoxN, and we have discovered two novel target genes
of SoxN that are expressed in denticle-producing cells and that are regulated
independently of Svb. We conclude that proper denticle morphogenesis requires
transcriptional regulation by both SoxN and Svb.
PMID- 28506987
TI - Development of the larval lymphatic system in zebrafish.
AB - The lymphatic vascular system is a hierarchically organized complex network
essential for tissue fluid homeostasis, immune trafficking and absorption of
dietary fats in the human body. Despite its importance, the assembly of the
lymphatic network is still not fully understood. The zebrafish is a powerful
model organism that enables study of lymphatic vessel development using high
resolution imaging and sophisticated genetic and experimental manipulation.
Although several studies have described early lymphatic development in the fish,
lymphatic development at later stages has not been completely elucidated. In this
study, we generated a new Tg(mrc1a:egfp)y251 transgenic zebrafish that uses a
mannose receptor, C type 1 (mrc1a) promoter to drive strong EGFP expression in
lymphatic vessels at all stages of development and in adult zebrafish. We used
this line to describe the assembly of the major vessels of the trunk lymphatic
vascular network, including the later-developing collateral cardinal, spinal,
superficial lateral and superficial intersegmental lymphatics. Our results show
that major trunk lymphatic vessels are conserved in the zebrafish, and provide a
thorough and complete description of trunk lymphatic vessel assembly.
PMID- 28506988
TI - Dmrt1 induces the male pathway in a turtle species with temperature-dependent sex
determination.
AB - The molecular mechanism underlying temperature-dependent sex determination (TSD)
has been a long-standing mystery; in particular, the thermosensitive genetic
triggers for gonadal sex differentiation are largely unknown. Here, we have
characterized a conserved DM domain gene, Dmrt1, in the red-eared slider turtle
Trachemys scripta (T. scripta), which exhibits TSD. We found that Dmrt1 has a
temperature-dependent, sexually dimorphic expression pattern, preceding gonadal
sex differentiation, and is capable of responding rapidly to temperature shifts
and aromatase inhibitor treatment. Most importantly, loss- and gain-of-function
analyses provide solid evidence that Dmrt1 is both necessary and sufficient to
initiate male development in T. scripta Furthermore, the DNA methylation dynamics
of the Dmrt1 promoter are tightly correlated with temperature and could mediate
the impact of temperature on sex determination. Collectively, our findings
demonstrate that Dmrt1 is a candidate master male sex-determining gene in this
TSD species, consistent with the idea that DM domain genes are conserved during
the evolution of sex determination mechanisms.
PMID- 28506990
TI - COUP-TFI mitotically regulates production and migration of dentate granule cells
and modulates hippocampal Cxcr4 expression.
AB - Development of the dentate gyrus (DG), the primary gateway for hippocampal
inputs, spans embryonic and postnatal stages, and involves complex morphogenetic
events. We have previously identified the nuclear receptor COUP-TFI as a novel
transcriptional regulator in the postnatal organization and function of the
hippocampus. Here, we dissect its role in DG morphogenesis by inactivating it in
either granule cell progenitors or granule neurons. Loss of COUP-TFI function in
progenitors leads to decreased granule cell proliferative activity, precocious
differentiation and increased apoptosis, resulting in a severe DG growth defect
in adult mice. COUP-TFI-deficient cells express high levels of the chemokine
receptor Cxcr4 and migrate abnormally, forming heterotopic clusters of
differentiated granule cells along their paths. Conversely, high COUP-TFI
expression levels downregulate Cxcr4 expression, whereas increased Cxcr4
expression in wild-type hippocampal cells affects cell migration. Finally, loss
of COUP-TFI in postmitotic cells leads to only minor and transient abnormalities,
and to normal Cxcr4 expression. Together, our results indicate that COUP-TFI is
required predominantly in DG progenitors for modulating expression of the Cxcr4
receptor during granule cell neurogenesis and migration.
PMID- 28506989
TI - FGF signaling refines Wnt gradients to regulate the patterning of taste papillae.
AB - The patterning of repeated structures is a major theme in developmental biology,
and the inter-relationship between spacing and size of such structures is an
unresolved issue. Fungiform papillae are repeated epithelial structures that
house taste buds on the anterior tongue. Here, we report that FGF signaling is a
crucial regulator of fungiform papillae development. We found that mesenchymal
FGF10 controls the size of the papillary area, while overall patterning remains
unchanged. Our results show that FGF signaling negatively affects the extent of
canonical Wnt signaling, which is the main activation pathway during fungiform
papillae development; however, this effect does not occur at the level of gene
transcription. Rather, our experimental data, together with computational
modeling, indicate that FGF10 modulates the range of Wnt effects, likely via
induction of Sostdc1 expression. We suggest that modification of the reach of Wnt
signaling could be due to local changes in morphogen diffusion, representing a
novel mechanism in this tissue context, and we propose that this phenomenon might
be involved in a broader array of mammalian developmental processes.
PMID- 28506992
TI - Reduced MAD2 levels dampen the apoptotic response to non-exchange sex chromosomes
and lead to sperm aneuploidy.
AB - In meiosis, non-exchange homologous chromosomes are at risk for mis-segregation
and should be monitored by the spindle assembly checkpoint (SAC) to avoid
formation of aneuploid gametes. Sex chromosome mis-segregation is particularly
common and can lead to sterility or to aneuploid offspring (e.g. individuals with
Turner or Klinefelter syndrome). Despite major implications for health and
reproduction, modifiers of meiotic SAC robustness and the subsequent apoptotic
response in male mammals remain obscure. Levels of SAC proteins, e.g. MAD2, are
crucial for normal checkpoint function in many experimental systems, but
surprisingly, apparently not in male meiosis, as indicated by the lack of
chromosome segregation defects reported earlier in Mad2+/- spermatocytes. To
directly test whether MAD2 levels impact the meiotic response to mis-segregating
chromosomes, we used Spo11beta-onlymb mice that are prone to non-exchange X-Y
chromosomes. We show that reduced MAD2 levels attenuate the apoptotic response to
mis-segregating sex chromosomes and allow the formation of aneuploid sperm. These
findings demonstrate that SAC protein levels are crucial for the efficient
elimination of aberrant spermatocytes.
PMID- 28506991
TI - Sonic hedgehog regulation of Foxf2 promotes cranial neural crest mesenchyme
proliferation and is disrupted in cleft lip morphogenesis.
AB - Cleft lip is one of the most common human birth defects, yet our understanding of
the mechanisms that regulate lip morphogenesis is limited. Here, we show in mice
that sonic hedgehog (Shh)-induced proliferation of cranial neural crest cell
(cNCC) mesenchyme is required for upper lip closure. Gene expression profiling
revealed a subset of Forkhead box (Fox) genes that are regulated by Shh signaling
during lip morphogenesis. During cleft pathogenesis, reduced proliferation in the
medial nasal process mesenchyme paralleled the domain of reduced Foxf2 and Gli1
expression. SHH ligand induction of Foxf2 expression was dependent upon Shh
pathway effectors in cNCCs, while a functional GLI-binding site was identified
downstream of Foxf2 Consistent with the cellular mechanism demonstrated for cleft
lip pathogenesis, we found that either SHH ligand addition or FOXF2
overexpression is sufficient to induce cNCC proliferation. Finally, analysis of a
large multi-ethnic human population with cleft lip identified clusters of single
nucleotide polymorphisms in FOXF2 These data suggest that direct targeting of
Foxf2 by Shh signaling drives cNCC mesenchyme proliferation during upper lip
morphogenesis, and that disruption of this sequence results in cleft lip.
PMID- 28506995
TI - Apical constriction is driven by a pulsatile apical myosin network in
delaminating Drosophila neuroblasts.
AB - Cell delamination is a conserved morphogenetic process important for the
generation of cell diversity and maintenance of tissue homeostasis. Here, we used
Drosophila embryonic neuroblasts as a model to study the apical constriction
process during cell delamination. We observe dynamic myosin signals both around
the cell adherens junctions and underneath the cell apical surface in the
neuroectoderm. On the cell apical cortex, the nonjunctional myosin forms flows
and pulses, which are termed medial myosin pulses. Quantitative differences in
medial myosin pulse intensity and frequency are crucial to distinguish
delaminating neuroblasts from their neighbors. Inhibition of medial myosin pulses
blocks delamination. The fate of a neuroblast is set apart from that of its
neighbors by Notch signaling-mediated lateral inhibition. When we inhibit Notch
signaling activity in the embryo, we observe that small clusters of cells undergo
apical constriction and display an abnormal apical myosin pattern. Together,
these results demonstrate that a contractile actomyosin network across the apical
cell surface is organized to drive apical constriction in delaminating
neuroblasts.
PMID- 28506993
TI - MAPK pathway control of stem cell proliferation and differentiation in the
embryonic pituitary provides insights into the pathogenesis of papillary
craniopharyngioma.
AB - Despite the importance of the RAS-RAF-MAPK pathway in normal physiology and
disease of numerous organs, its role during pituitary development and
tumourigenesis remains largely unknown. Here, we show that the over-activation of
the MAPK pathway, through conditional expression of the gain-of-function alleles
BrafV600E and KrasG12D in the developing mouse pituitary, results in severe
hyperplasia and abnormal morphogenesis of the gland by the end of gestation. Cell
lineage commitment and terminal differentiation are disrupted, leading to a
significant reduction in numbers of most of the hormone-producing cells before
birth, with the exception of corticotrophs. Of note, Sox2+ stem cells and
clonogenic potential are drastically increased in the mutant pituitaries.
Finally, we reveal that papillary craniopharyngioma (PCP), a benign human
pituitary tumour harbouring BRAF p.V600E also contains Sox2+ cells with sustained
proliferative capacity and disrupted pituitary differentiation. Together, our
data demonstrate a crucial function of the MAPK pathway in controlling the
balance between proliferation and differentiation of Sox2+ cells and suggest that
persistent proliferative capacity of Sox2+ cells may underlie the pathogenesis of
PCP.
PMID- 28506994
TI - Gain-of-function mutations in Aqp3a influence zebrafish pigment pattern formation
through the tissue environment.
AB - The development of the pigmentation pattern in zebrafish is a tightly regulated
process that depends on both the self-organizing properties of pigment cells and
extrinsic cues from other tissues. Many of the known mutations that alter the
pattern act cell-autonomously in pigment cells, and our knowledge about external
regulators is limited. Here, we describe novel zebrafish mau mutants, which
encompass several dominant missense mutations in Aquaporin 3a (Aqp3a) that lead
to broken stripes and short fins. A loss-of-function aqp3a allele, generated by
CRISPR-Cas9, has no phenotypic consequences, demonstrating that Aqp3a is
dispensable for normal development. Strikingly, the pigment cells from dominant
mau mutants are capable of forming a wild-type pattern when developing in a wild
type environment, but the surrounding tissues in the mutants influence pigment
cell behaviour and interfere with the patterning process. The mutated amino acid
residues in the dominant alleles line the pore surface of Aqp3a and influence
pore permeability. These results demonstrate an important effect of the tissue
environment on pigment cell behaviour and, thereby, on pattern formation.
PMID- 28506997
TI - The phosphatase Pgam5 antagonizes Wnt/beta-Catenin signaling in embryonic
anterior-posterior axis patterning.
AB - The scaffold protein Dishevelled is a central intracellular component of Wnt
signaling pathways. Various kinases have been described that regulate and
modulate Wnt signaling through phosphorylation of Dishevelled. However, besides
general protein phosphatases 1 and 2 (PP1 and PP2), no specific protein
phosphatases have been identified. Here, we report on the identification and
functional characterization of the protein phosphatase Pgam5 in vitro and in vivo
in Xenopus Pgam5 is a novel antagonist of Wnt/beta-Catenin signaling in human
cells and Xenopus embryogenesis. In early development, Pgam5 is essential for
head formation, and for establishing and maintaining the Wnt/beta-Catenin
signaling gradient that patterns the anterior-posterior body axis. Inhibition of
Wnt/beta-Catenin signaling and developmental function depend on Pgam5 phosphatase
activity. We show that Pgam5 interacts with Dishevelled2 and that Dishevelled2 is
a substrate of Pgam5. Pgam5 mediates a marked decrease in Dishevelled2
phosphorylation in the cytoplasm and in the nucleus, as well as decreased
interaction between Dishevelled2, Tcf1 and beta-Catenin, indicating that Pgam5
regulates Dishevelled function upstream and downstream of beta-Catenin
stabilization.
PMID- 28506996
TI - RET-mediated glial cell line-derived neurotrophic factor signaling inhibits mouse
prostate development.
AB - In humans and rodents, the prostate gland develops from the embryonic urogenital
sinus (UGS). The androgen receptor (AR) is thought to control the expression of
morphogenetic genes in inductive UGS mesenchyme, which promotes proliferation and
cytodifferentiation of the prostatic epithelium. However, the nature of the AR
regulated morphogenetic genes and the mechanisms whereby AR controls prostate
development are not understood. Glial cell line-derived neurotrophic factor
(GDNF) binds GDNF family receptor alpha1 (GFRalpha1) and signals through
activation of RET tyrosine kinase. Gene disruption studies in mice have revealed
essential roles for GDNF signaling in development; however, its role in prostate
development is unexplored. Here, we establish novel roles of GDNF signaling in
mouse prostate development. Using an organ culture system for prostate
development and Ret mutant mice, we demonstrate that RET-mediated GDNF signaling
in UGS increases proliferation of mesenchyme cells and suppresses androgen
induced proliferation and differentiation of prostate epithelial cells,
inhibiting prostate development. We also identify Ar as a GDNF-repressed gene and
Gdnf and Gfralpha1 as androgen-repressed genes in UGS, thus establishing
reciprocal regulatory crosstalk between AR and GDNF signaling in prostate
development.
PMID- 28506998
TI - Fgf10 and Sox9 are essential for the establishment of distal progenitor cells
during mouse salivary gland development.
AB - Salivary glands are formed by branching morphogenesis with epithelial progenitors
forming a network of ducts and acini (secretory cells). During this process,
epithelial progenitors specialise into distal (tips of the gland) and proximal
(the stalk region) identities that produce the acini and higher order ducts,
respectively. Little is known about the factors that regulate progenitor
expansion and specialisation in the different parts of the gland. Here, we show
that Sox9 is involved in establishing the identity of the distal compartment
before the initiation of branching morphogenesis. Sox9 is expressed throughout
the gland at the initiation stage before becoming restricted to the distal
epithelium from the bud stage and throughout branching morphogenesis. Deletion of
Sox9 in the epithelium results in loss of the distal epithelial progenitors, a
reduction in proliferation and a subsequent failure in branching. We demonstrate
that Sox9 is positively regulated by mesenchymal Fgf10, a process that requires
active Erk signalling. These results provide new insights into the factors
required for the expansion of salivary gland epithelial progenitors, which can be
useful for organ regeneration therapy.
PMID- 28506999
TI - Btbd7 is essential for region-specific epithelial cell dynamics and branching
morphogenesis in vivo.
AB - Branching morphogenesis of developing organs requires coordinated but poorly
understood changes in epithelial cell-cell adhesion and cell motility. We report
that Btbd7 is a crucial regulator of branching morphogenesis in vivo. Btbd7
levels are elevated in peripheral cells of branching epithelial end buds, where
it enhances cell motility and cell-cell adhesion dynamics. Genetic ablation of
Btbd7 in mice disrupts branching morphogenesis of salivary gland, lung and
kidney. Btbd7 knockout results in more tightly packed outer bud cells, which
display stronger E-cadherin localization, reduced cell motility and decreased
dynamics of transient cell separations associated with cleft formation; inner bud
cells remain unaffected. Mechanistic analyses using in vitro MDCK cells to mimic
outer bud cell behavior establish that Btbd7 promotes loss of E-cadherin from
cell-cell adhesions with enhanced migration and transient cell separation. Btbd7
can enhance E-cadherin ubiquitination, internalization, and degradation in MDCK
and peripheral bud cells for regulating cell dynamics. These studies show how a
specific regulatory molecule, Btbd7, can function at a local region of developing
organs to regulate dynamics of cell adhesion and motility during epithelial
branching morphogenesis.
PMID- 28507000
TI - The cell wall-localized atypical beta-1,3 glucanase ZERZAUST controls tissue
morphogenesis in Arabidopsis thaliana.
AB - Orchestration of cellular behavior in plant organogenesis requires integration of
intercellular communication and cell wall dynamics. The underlying signaling
mechanisms are poorly understood. Tissue morphogenesis in Arabidopsis depends on
the receptor-like kinase STRUBBELIG. Mutations in ZERZAUST were previously shown
to result in a strubbelig-like mutant phenotype. Here, we report on the molecular
identification and functional characterization of ZERZAUST We show that ZERZAUST
encodes a putative GPI-anchored beta-1,3 glucanase suggested to degrade the cell
wall polymer callose. However, a combination of in vitro, cell biological and
genetic experiments indicate that ZERZAUST is not involved in the regulation of
callose accumulation. Nonetheless, Fourier-transformed infrared-spectroscopy
revealed that zerzaust mutants show defects in cell wall composition.
Furthermore, the results indicate that ZERZAUST represents a mobile apoplastic
protein, and that its carbohydrate-binding module family 43 domain is required
for proper subcellular localization and function whereas its GPI anchor is
dispensable. Our collective data reveal that the atypical beta-1,3 glucanase
ZERZAUST acts in a non-cell-autonomous manner and is required for cell wall
organization during tissue morphogenesis.
PMID- 28507003
TI - Surgeon is struck off after three "never events".
PMID- 28507001
TI - p38 MAPK as an essential regulator of dorsal-ventral axis specification and
skeletogenesis during sea urchin development: a re-evaluation.
AB - Dorsal-ventral axis formation in the sea urchin embryo relies on the asymmetrical
expression of the TGFbeta Nodal. The p38-MAPK pathway has been proposed to be
essential for dorsal-ventral axis formation by acting upstream of nodal
expression. Here, we report that, in contrast to previous studies that used
pharmacological inhibitors of p38, manipulating the activity of p38 by genetic
means has no obvious impact on morphogenesis. Instead, we discovered that p38
inhibitors strongly disrupt specification of all germ layers by blocking
signalling from the Nodal receptor and by interfering with the ERK pathway.
Strikingly, while expression of a mutant p38 that is resistant to SB203580 did
not rescue dorsal-ventral axis formation or skeletogenesis in embryos treated
with this inhibitor, expression of mutant Nodal receptors that are resistant to
SB203580 fully restored nodal expression in SB203580-treated embryos. Taken
together, these results establish that p38 activity is not required for dorsal
ventral axis formation through nodal expression nor for skeletogenesis. Our
results prompt a re-evaluation of the conclusions of several recent studies that
linked p38 activity to dorsal-ventral axis formation and to patterning of the
skeleton.
PMID- 28507002
TI - Neuregulin 1 Allosterically Enhances the Antitumor Effects of the Noncompeting
Anti-HER3 Antibody 9F7-F11 by Increasing Its Binding to HER3.
AB - Exploratory clinical trials using therapeutic anti-HER3 antibodies strongly
suggest that neuregulin (NRG1; HER3 ligand) expression at tumor sites is a
predictive biomarker of anti-HER3 antibody efficacy in cancer. We hypothesized
that in NRG1-expressing tumors, where the ligand is present before antibody
treatment, anti-HER3 antibodies that do not compete with NRG1 for receptor
binding have a higher receptor-neutralizing action than antibodies competing with
the ligand for binding to HER3. Using time-resolved-fluorescence energy transfer
(TR-FRET), we demonstrated that in the presence of recombinant NRG1, binding of
9F7-F11 (a nonligand-competing anti-HER3 antibody) to HER3 is increased, whereas
that of ligand-competing anti-HER3 antibodies (H4B-121, U3-1287, Ab#6,
Mab205.10.2, and MOR09825) is decreased. Moreover, 9F7-F11 showed higher efficacy
than antibodies that compete with the ligand for binding to HER3. Specifically,
9F7-F11 inhibition of cell proliferation and of HER3/AKT/ERK1/2 phosphorylation
as well as 9F7-F11-dependent cell-mediated cytotoxicity were higher in cancer
cells preincubated with recombinant NRG1 compared with cells directly exposed to
the anti-HER3 antibody. This translated in vivo into enhanced growth inhibition
of NRG1-expressing BxPC3 pancreatic, A549 lung, and HCC-1806 breast cell tumor
xenografts in mice treated with 9F7-F11 compared with H4B-121. Conversely, both
antibodies had similar antitumor effect in NRG1-negative HPAC pancreatic
carcinoma cells. In conclusion, the allosteric modulator 9F7-F11 shows increased
anticancer effectiveness in the presence of NRG1 and thus represents a novel
treatment strategy for NRG1-addicted tumors. Mol Cancer Ther; 16(7); 1312-23.
(c)2017 AACR.
PMID- 28507005
TI - Perspective: What Makes It So Difficult to Mitigate Worldwide Anemia Prevalence?
AB - Anemia can be related to decreased production or increased loss of erythrocytes,
or both, leading to many underlying and often overlapping causes. A largely
cereal-based diet with plenty of phytates, polyphenols, and other ligands that
inhibit intestinal iron absorption predominated in preindustrial Europe and
predominates in present-day developing countries alike. In both situations, we
find poor hygienic conditions, which frequently lead to anemia of inflammation.
The large number of possible causes and their interaction shows why it is so
difficult to mitigate anemia prevalence. Diagnostic biomarkers are required to
differentiate the different types of anemia and to treat them appropriately. Some
of them are well established in adults [e.g., concentrations of serum ferritin,
soluble transferrin receptor (sTfR), and serum iron or the ratio of sTfR to log
ferritin]. Others, such as serum hepcidin, hold considerable promise, although
they are not yet widely used. A particular issue is to establish reference values
for biomarkers in infants and children at different ages. The fact that resource
rich postindustrial societies have a very low prevalence of iron-deficiency
anemia offers hope that common types of anemia can be eliminated. In contrast,
inborn forms of anemia, such as thalassemia, and anemias related to underlying
diseases (e.g., bleeding tumors or peptic ulcers, gynecologic blood losses, or
renal diseases) require an operational health system to be addressed
appropriately.
PMID- 28507006
TI - Perspective: Gluten-Free Products for Patients with Celiac Disease Should Not
Contain Trace Levels.
PMID- 28507008
TI - Flavones: Food Sources, Bioavailability, Metabolism, and Bioactivity.
AB - Flavones are a class of flavonoids that are a subject of increasing interest
because of their biological activities in vitro and in vivo. This article reviews
the major sources of flavones and their concentrations in food and beverages,
which vary widely between studies. It also covers the roles of flavones in
plants, the influence of growing conditions on their concentrations, and their
stability during food processing. The absorption and metabolism of flavones are
also reviewed, in particular the intestinal absorption of both O- and C
glycosides. Pharmacokinetic studies in both animals and humans are described,
comparing differences between species and the effects of glycosylation on
bioavailability. Biological activity in animal models and human dietary
intervention studies is also reviewed. A better understanding of flavone sources
and bioavailability is needed to understand mechanisms of action and nutritional
intervention.
PMID- 28507007
TI - Perspective: A Historical and Scientific Perspective of Sugar and Its Relation
with Obesity and Diabetes.
AB - Fructose-containing added sugars, such as sucrose and high-fructose corn syrup,
have been experimentally, epidemiologically, and clinically shown to be involved
in the current epidemics of obesity and diabetes. Here we track this history of
intake of sugar as it relates to these epidemics. Key experimental studies that
have identified mechanisms by which fructose causes obesity and diabetes are
reviewed, as well as the evidence that the uricase mutation that occurred in the
mid-Miocene in ancestral humans acted as a "thrifty gene" that increases our
susceptibility for fructose-associated obesity today. We briefly review recent
evidence that obesity can also be induced by nondietary sources of fructose, such
as from the metabolism of glucose (from high-glycemic carbohydrates) through the
polyol pathway. These studies suggest that fructose-induced obesity is driven by
engagement of a "fat switch" and provide novel insights into new approaches for
the prevention and treatment of these important diseases.
PMID- 28507009
TI - A Systematic Examination of the Association between Parental and Child Obesity
across Countries.
AB - Childhood obesity has become a global epidemic. Parents can have an important
influence on their children's health behaviors and weight status. Many studies
have examined the association between parental and childhood weight status.
However, much heterogeneity between studies exists, and the parent-child (P-C)
association in obesity has varied. The purpose of this systematic examination and
meta-analysis was to examine the strength and variation of the P-C association in
obesity and to identify factors (e.g., demographic characteristics and country's
economic level) that may influence this association. PubMed was searched for
relevant studies published between January 2000 and July 2015. Thirty-two studies
from 21 countries met inclusion criteria; 27 reported ORs for the P-C obesity
association and were included in a meta-analysis. The meta-analysis showed a
strong P-C obesity association (pooled OR: 2.22; 95% CI: 2.09, 2.36), which
varied by type of P-C pair (i.e., parents-child, father-child, and mother-child),
child age, parent and child weight status, and the country's economic level.
Stronger associations were shown in older children than in younger children (beta
+/- SE: 0.02 +/- 0.01), in both parents than in father only (beta +/- SE: 0.51 +/
0.11) or mother only (beta +/- SE: 0.38 +/- 0.11), in parental obesity (beta +/-
SE: 0.26 +/- 0.10) and child obesity (beta +/- SE: 0.28 +/- 0.12) than in
parental and child overweight, and in high- than in middle-income countries (beta
+/- SE: 0.23 +/- 0.08). Thus, research from multiple countries shows significant
P-C associations in weight status, but this association varies by child age, type
of P-C pair, weight status, and the country's economic level. Results suggest
that families and parents should be a key target for obesity intervention
efforts.
PMID- 28507010
TI - A Systematic Review of Application and Effectiveness of mHealth Interventions for
Obesity and Diabetes Treatment and Self-Management.
AB - The use of mobile and wireless technologies and wearable devices for improving
health care processes and outcomes (mHealth) is promising for health promotion
among patients with chronic diseases such as obesity and diabetes. This study
comprehensively examined published mHealth intervention studies for obesity and
diabetes treatment and management to assess their effectiveness and provide
recommendations for future research. We systematically searched PubMed for
mHealth-related studies on diabetes and obesity treatment and management
published during 2000-2016. Relevant information was extracted and analyzed.
Twenty-four studies met inclusion criteria and varied in terms of sample size,
ethnicity, gender, and age of the participating patients and length of follow-up.
The mHealth interventions were categorized into 3 types: mobile phone text
messaging, wearable or portable monitoring devices, and applications running on
smartphones. Primary outcomes included weight loss (an average loss ranging from
1.97 kg in 16 wk to -7.1 kg in 5 wk) or maintenance and blood glucose reduction
(an average decrease of glycated hemoglobin ranging from -0.4% in 10 mo to -1.9%
in 12 mo); main secondary outcomes included behavior changes and patient
perceptions such as self-efficacy and acceptability of the intervention programs.
More than 50% of studies reported positive effects of interventions based on
primary outcomes. The duration or length of intervention ranged from 1 wk to 24
mo. However, most studies included small samples and short intervention periods
and did not use rigorous data collection or analytic approaches. Although some
studies suggest that mHealth interventions are effective and promising, most are
pilot studies or have limitations in their study designs. There is an essential
need for future studies that use larger study samples, longer intervention (>= 6
mo) and follow-up periods (>= 6 mo), and integrative and personalized innovative
mobile technologies to provide comprehensive and sustainable support for patients
and health service providers.
PMID- 28507011
TI - Influence of Diet in Multiple Sclerosis: A Systematic Review.
AB - Nutrition is considered to be a possible factor in the pathogenesis of the
neurological disease multiple sclerosis (MS). Nutrition intervention studies
suggest that diet may be considered as a complementary treatment to control the
progression of the disease; a systematic review of the literature on the
influence of diet on MS was therefore conducted. The literature search was
conducted by using Medlars Online International Literature (MEDLINE) via PubMed
and Scopus. Forty-seven articles met the inclusion criteria. The reviewed
articles assessed the relations between macro- and micronutrient intakes and MS
incidence. The patients involved used alternative therapies (homeopathy),
protocolized diets that included particular foods (herbal products such as grape
seed extract, ginseng, blueberries, green tea, etc.), or dietary supplements such
as vitamin D, carnitine, melatonin, or coenzyme Q10. Current studies suggest that
high serum concentrations of vitamin D, a potent immunomodulator, may decrease
the risk of MS and the risk of relapse and new lesions, while improving brain
lesions and timed tandem walking. Experimental evidence suggests that serum
vitamin D concentration is lower during MS relapses than in remission and is
associated with a greater degree of disability [Expanded Disability Status Scale
(EDSS) score >3]. The findings suggest that circulating vitamin D concentrations
can be considered a biomarker of MS and supplemental vitamin D can be used
therapeutically. Other studies point to a negative correlation between serum
vitamin B-12 concentrations and EDSS score. Vitamin B-12 has fundamental roles in
central nervous system function, especially in the methionine synthase-mediated
conversion of homocysteine to methionine, which is essential for DNA and RNA
synthesis. Therefore, vitamin B-12 deficiency may lead to an increase in the
concentration of homocysteine. Further research is clearly necessary to determine
whether treatment with vitamin B-12 supplements delays MS progression.
PMID- 28507012
TI - Dietary Factors Promoting Brown and Beige Fat Development and Thermogenesis.
AB - Brown adipose tissue (BAT) is a specialized fat tissue that has a high capacity
to dissociate cellular respiration from ATP utilization, resulting in the release
of stored energy as heat. Adult humans possess a substantial amount of BAT in the
form of constitutively active brown fat or inducible beige fat. BAT activity in
humans is inversely correlated with adiposity, blood glucose concentrations, and
insulin sensitivity; this suggests that strategies aimed at BAT-mediated
bioenergetics are an attractive therapeutic target in combating the continuing
epidemic of obesity and diabetes. Despite advances in knowledge regarding the
developmental lineage and transcriptional regulators of brown and beige
adipocytes, our current understanding of environmental modifiers of BAT
thermogenesis, such as diet, is limited. In this review, we consolidated the
latest research on dietary molecules that may serve to promote BAT thermogenesis.
Here, we summarized the thermogenic function of selected phytochemicals (e.g.,
capsaicin, resveratrol, curcumin, green tea, and berberine), dietary fatty acids
(e.g., fish oil and conjugated linoleic acids), and all-trans retinoic acid, a
vitamin A metabolite. We also delineated the proposed mechanisms whereby these
dietary molecules promote BAT activity and/or browning of white adipose tissue.
Characterizing thermogenic dietary factors may offer novel insight into revising
nutritional intervention strategies aimed at obesity and diabetes prevention and
management.
PMID- 28507017
TI - Erratum for Rippe. The metabolic and endocrine response and health implications
of consuming sugar-sweetened beverages: findings from recent randomized
controlled trials. Adv Nutr 2013;4:677-86.
PMID- 28507018
TI - Erratum for Rippe and Angelopoulos. Fructose-containing sugars and cardiovascular
disease. Adv Nutr 2015;6:430-9.
PMID- 28507016
TI - Manganese.
PMID- 28507013
TI - Mechanisms of Action of Probiotics and the Gastrointestinal Microbiota on Gut
Motility and Constipation.
AB - Constipation is a common and burdensome gastrointestinal disorder that may result
from altered gastrointestinal motility. The effect of probiotics on constipation
has been increasingly investigated in both animal and human studies, showing
promising results. However, there is still uncertainty regarding the mechanisms
of action of probiotics on gut motility and constipation. Several factors are
vital to normal gut motility, including immune and nervous system function, bile
acid metabolism and mucus secretion, and the gastrointestinal microbiota and
fermentation; an imbalance or dysfunction in any of these components may
contribute to aberrant gut motility and, consequently, symptoms of constipation.
For example, adults with functional constipation have significantly decreased
numbers of bifidobacteria (with one study showing a mean difference of 1 log10/g)
and lactobacilli (mean difference, 1.4 log10/g) in stool samples, as well as
higher breath methane, compared with control subjects. Modifying the gut luminal
environment with certain probiotic strains may affect motility and secretion in
the gut and, hence, provide a benefit for patients with constipation. Therefore,
this review explores the mechanisms through which probiotics may exert an effect
on gut motility and constipation. Nevertheless, the majority of current evidence
is derived from animal studies, and therefore, further human studies are needed
to determine the mechanisms through specific probiotic strains that might be
effective in constipation.
PMID- 28507014
TI - Associations between Breastfeeding and Maternal Responsiveness: A Systematic
Review of the Literature.
AB - Recent recommendations and prevention programs have focused on the promotion of
responsive feeding during infancy, but more research is needed to understand best
practices for fostering responsive feeding during early life. The objective of
this systematic review was to synthesize the accumulating bodies of evidence
aimed at understanding associations between mothers' feeding experiences and
responsive feeding in an attempt to clarify the nature of associations between
feeding mode and responsive feeding. A literature search was conducted between
January and October 2016; articles were collected from PsychINFO, Medline, and
CINAHL, as well as from references in published research and reviews. Article
inclusion criteria were as follows: 1) empirical research, 2) included a measure
of infant feeding, 3) included a measure of maternal responsiveness, 4) study
conducted in human participants, 5) available in English, and 6) study conducted
in a developed and/or high-income country. Forty-three studies were identified.
Cross-sectional observational studies consistently reported greater
responsiveness among breastfeeding mothers than among formula-/bottle-feeding
mothers. In addition, longitudinal studies showed that longer breastfeeding
durations predicted lower use of nonresponsive feeding practices during later
childhood, and some, but not all, found that breastfeeding mothers showed greater
increases in responsiveness across infancy than did formula-/bottle-feeding
mothers. However, a limited number of longitudinal studies also reported that
greater responsiveness during early infancy predicted longer breastfeeding
durations. A common limitation among these studies is the correlational nature of
their designs and lack of prenatal measures of maternal responsiveness, which
hinders our understanding of causal mechanisms. Although 2 randomized clinical
trials aimed at promoting maternal responsiveness did not find effects of the
intervention on breastfeeding outcomes, these findings were limited by the way in
which breastfeeding outcomes were assessed. In sum, although there is consistent
evidence for an association between breastfeeding and responsive feeding, more
research is needed to better understand the mechanisms underlying this
association.
PMID- 28507019
TI - Major global cyber-attack hits NHS and delays treatment.
PMID- 28507015
TI - Preserving Healthy Muscle during Weight Loss.
AB - Weight loss is the cornerstone of therapy for people with obesity because it can
ameliorate or completely resolve the metabolic risk factors for diabetes,
coronary artery disease, and obesity-associated cancers. The potential health
benefits of diet-induced weight loss are thought to be compromised by the weight
loss-associated loss of lean body mass, which could increase the risk of
sarcopenia (low muscle mass and impaired muscle function). The objective of this
review is to provide an overview of what is known about weight-loss-induced
muscle loss and its implications for overall physical function (e.g., ability to
lift items, walk, and climb stairs). The currently available data in the
literature show the following: 1) compared with persons with normal weight, those
with obesity have more muscle mass but poor muscle quality; 2) diet-induced
weight loss reduces muscle mass without adversely affecting muscle strength; 3)
weight loss improves global physical function, most likely because of reduced fat
mass; 4) high protein intake helps preserve lean body and muscle mass during
weight loss but does not improve muscle strength and could have adverse effects
on metabolic function; 5) both endurance- and resistance-type exercise help
preserve muscle mass during weight loss, and resistance-type exercise also
improves muscle strength. We therefore conclude that weight-loss therapy,
including a hypocaloric diet with adequate (but not excessive) protein intake and
increased physical activity (particularly resistance-type exercise), should be
promoted to maintain muscle mass and improve muscle strength and physical
function in persons with obesity.
PMID- 28507020
TI - TGF-beta Family Signaling in Mesenchymal Differentiation.
AB - Mesenchymal stem cells (MSCs) can differentiate into several lineages during
development and also contribute to tissue homeostasis and regeneration, although
the requirements for both may be distinct. MSC lineage commitment and progression
in differentiation are regulated by members of the transforming growth factor
beta (TGF-beta) family. This review focuses on the roles of TGF-beta family
signaling in mesenchymal lineage commitment and differentiation into osteoblasts,
chondrocytes, myoblasts, adipocytes, and tenocytes. We summarize the reported
findings of cell culture studies, animal models, and interactions with other
signaling pathways and highlight how aberrations in TGF-beta family signaling can
drive human disease by affecting mesenchymal differentiation.
PMID- 28507022
TI - Loss of E-Cadherin-Dependent Cell-Cell Adhesion and the Development and
Progression of Cancer.
AB - Classical cadherins are the key molecules that control cell-cell adhesion.
Notwithstanding this function, it is also clear that classical cadherins are more
than just the "glue" that keeps the cells together. Cadherins are essential
regulators of tissue homeostasis that govern multiple facets of cellular function
and development, by transducing adhesive signals to a complex network of
signaling effectors and transcriptional programs. In cancer, cadherins are often
inactivated or functionally inhibited, resulting in disease development and/or
progression. This review focuses on E-cadherin and its causal role in the
development and progression of breast and gastric cancer. We provide a summary of
the biochemical consequences and consider the conceptual impact of early
(mutational) E-cadherin loss in cancer. We advocate that carcinomas driven by E
cadherin loss should be considered "actin-diseases," caused by the specific
disruption of the E-cadherin-actin connection and a subsequent dependence on
sustained actomyosin contraction for tumor progression. Based on the available
data from mouse and human studies we discuss opportunities for targeted clinical
intervention.
PMID- 28507021
TI - Cell Biology of Tight Junction Barrier Regulation and Mucosal Disease.
AB - Mucosal surfaces are lined by epithelial cells. In the intestine, the epithelium
establishes a selectively permeable barrier that supports nutrient absorption and
waste secretion while preventing intrusion by luminal materials. Intestinal
epithelia therefore play a central role in regulating interactions between the
mucosal immune system and luminal contents, which include dietary antigens, a
diverse intestinal microbiome, and pathogens. The paracellular space is sealed by
the tight junction, which is maintained by a complex network of protein
interactions. Tight junction dysfunction has been linked to a variety of local
and systemic diseases. Two molecularly and biophysically distinct pathways across
the intestinal tight junction are selectively and differentially regulated by
inflammatory stimuli. This review discusses the mechanisms underlying these
events, their impact on disease, and the potential of using these as paradigms
for development of tight junction-targeted therapeutic interventions.
PMID- 28507023
TI - Increases in Biomarkers of Hyperglycemia With Age in the Atherosclerosis Risk in
Communities (ARIC) Study.
PMID- 28507024
TI - Cutting Edge: Differential Fine-Tuning of IL-2- and IL-15-Dependent Functions by
Targeting Their Common IL-2/15Rbeta/gammac Receptor.
AB - Interleukin 2 and IL-15 are two closely related cytokines, displaying important
functions in the immune system. They share the heterodimeric CD122/CD132 receptor
to deliver their signals within target cells. Their specificity of action is
conferred by their alpha receptor chains, IL-2Ralpha and IL-15Ralpha. By
combining an increased affinity for CD122 and an impaired recruitment of CD132,
we have generated an original molecule named IL-2Rbeta/gamma (CD122/CD132)
inhibitor (BiG), targeting the CD122/CD132 receptor. BiG efficiently inhibited IL
15- and IL-2-dependent functions of primary cells, including CD8 T and NK cells,
in vitro and in vivo. We also report a differential dynamic of action of these
cytokines by highlighting a major role played by the IL-2Ralpha receptor.
Interestingly, due to the presence of IL-2Ralpha, BiG had no impact on IL-2
dependent regulatory T cell proliferation. Thus, by acting as a fine switch in
the immune system, BiG emphasizes the differential roles of these two cytokines.
PMID- 28507025
TI - Cutting Edge: Defective Aerobic Glycolysis Defines the Distinct Effector Function
in Antigen-Activated CD8+ Recent Thymic Emigrants.
AB - Recent thymic emigrants (RTEs) are the youngest peripheral T cells that have
completed thymic selection and egress to the lymphoid periphery. RTEs are
functionally distinct from their more mature but still naive T cell counterparts,
because they exhibit dampened proliferation and reduced cytokine production upon
activation. In this article, we show that, compared with more mature but still
naive T cells, RTEs are impaired in their ability to perform aerobic glycolysis
following activation. Impaired metabolism underlies the reduced IFN-gamma
production observed in activated RTEs. This failure to undergo Ag-induced aerobic
glycolysis is caused by reduced mTORC1 activity and diminished Myc induction in
RTEs. Critically, exogenous IL-2 restores Myc expression in RTEs, driving aerobic
glycolysis and IFN-gamma production to the level of mature T cells. These results
reveal a previously unknown metabolic component to postthymic T cell maturation.
PMID- 28507027
TI - Mycobacterium tuberculosis Lipoprotein MPT83 Induces Apoptosis of Infected
Macrophages by Activating the TLR2/p38/COX-2 Signaling Pathway.
AB - Tuberculosis caused by Mycobacterium tuberculosis continues to pose a serious
global health threat. The attenuated Mycobacterium bovis bacillus Calmette
Guerin, as the only licensed vaccine, has limited protective efficacy against TB.
The development of more effective antituberculosis vaccines is urgent and demands
for further identification and understanding of M. tuberculosis Ags. MPT83
(Rv2873), a secreted mycobacterial lipoprotein, has been applied into subunit
vaccine development and shown protective effects against M. tuberculosis
infection in animals; however, the understanding of the underlying mechanism is
limited. In present study, we systematically studied the effect of MPT83 on
macrophage apoptosis by constructing Mycobacterium smegmatis strain
overexpressing MPT83 (MS_MPT83) and purifying rMPT83 protein. We found that MPT83
induced apoptosis in both human and mouse macrophages. MPT83 induced
cyclooxygenase-2 (COX-2) expression at both the transcriptional and protein
levels in macrophages, whereas silencing or inhibiting COX-2 blocked rMPT83
induced apoptosis or the enhanced apoptotic response to MS_MPT83 in comparison
with M. smegmatis transfected with pMV261 vector (MS_Vec), indicating that COX-2
is required for MPT83-induced apoptosis. Additionally, tlr2 deficiency led to
significant reduction of COX-2 expression, accompanied by less apoptosis in
macrophages stimulated with rMPT83 or infected with MS_MPT83. Moreover, the
activation of p38 accounted for MPT83-induced COX-2 expression. Finally, lower
bacteria burdens in the lungs and spleens and enhanced survival were observed in
mice i.v. infected with MS_MPT83 compared with MS_Vec. Taken together, our
results established a proapoptotic effect of MPT83 and identified the
TLR2/p38/COX-2 axis in MPT83-induced macrophage apoptosis.
PMID- 28507028
TI - RIG-I-like Receptor Triggering by Dengue Virus Drives Dendritic Cell Immune
Activation and TH1 Differentiation.
AB - Dengue virus (DENV) causes 400 million infections annually and is one of several
viruses that can cause viral hemorrhagic fever, which is characterized by
uncontrolled immune activation resulting in high fever and internal bleeding.
Although the underlying mechanisms are unknown, massive cytokine secretion is
thought to be involved. Dendritic cells (DCs) are the main target cells of DENV,
and we investigated their role in DENV-induced cytokine production and adaptive
immune responses. DENV infection induced DC maturation and secretion of IL-1beta,
IL-6, and TNF. Inhibition of DENV RNA replication abrogated these responses.
Notably, silencing of RNA sensors RIG-I or MDA5 abrogated DC maturation, as well
as cytokine responses by DENV-infected DCs. DC maturation was induced by type I
IFN responses because inhibition of IFN-alpha/beta receptor signaling abrogated
DENV-induced DC maturation. Moreover, DENV infection of DCs resulted in CCL2,
CCL3, and CCL4 expression, which was abrogated after RIG-I and MDA5 silencing.
DCs play an essential role in TH cell differentiation, and we show that RIG-I and
MDA5 triggering by DENV leads to TH1 polarization, which is characterized by high
levels of IFN-gamma. Notably, cytokines IL-6, TNF, and IFN-gamma and chemokines
CCL2, CCL3, and CCL4 have been associated with disease severity, endothelial
dysfunction, and vasodilation. Therefore, we identified RIG-I and MDA5 as
critical players in innate and adaptive immune responses against DENV, and
targeting these receptors has the potential to decrease hemorrhagic fever in
patients.
PMID- 28507026
TI - Lineage-Specific Metabolic Properties and Vulnerabilities of T Cells in the
Demyelinating Central Nervous System.
AB - Multiple sclerosis (MS) is a disease that is characterized by immune-mediated
destruction of CNS myelin. Current MS therapies aim to block peripheral immune
cells from entering the CNS. Although these treatments limit new inflammatory
activity in the CNS, no treatment effectively prevents long-term disease
progression and disability accumulation in MS patients. One explanation for this
paradox is that current therapies are ineffective at targeting immune responses
already present in the CNS. To this end, we sought to understand the metabolic
properties of T cells that mediate ongoing inflammation in the demyelinating CNS.
Using experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, a well
studied model of MS, we showed that the CD4+ and CD8+ T cells that invade the EAE
CNS are highly glycolytic. Elevated glycolytic rates in T cells isolated from the
EAE CNS correlate with upregulated expression of glycolytic machinery and is
essential for inflammatory responses to myelin. Surprisingly, we found that an
inhibitor of GAPDH, 3-bromopyruvic acid (3-BrPa), blocks IFN-gamma, but not IL
17A, production in immune cells isolated from the EAE CNS. Indeed, in vitro
studies confirmed that the production of IFN-gamma by differentiated Th1 cells is
more sensitive to 3-BrPa than is the production of IL-17A by Th17 cells. Finally,
in transfer models of EAE, 3-BrPa robustly attenuates the encephalitogenic
potential of EAE-driving immune cells. To our knowledge, these data are among the
first to demonstrate the metabolic properties of T cells in the demyelinating CNS
in vivo.
PMID- 28507029
TI - CD63-Mediated Antigen Delivery into Extracellular Vesicles via DNA Vaccination
Results in Robust CD8+ T Cell Responses.
AB - DNA vaccines are attractive immunogens for priming humoral and cellular immune
responses to the encoded Ag. However, their ability to induce Ag-specific CD8+ T
cell responses requires improvement. Among the strategies for improving DNA
vaccine immunogenicity are booster vaccinations, alternate vaccine formulations,
electroporation, and genetic adjuvants, but few, such as extracellular vesicles
(EVs), target natural Ag delivery systems. By focusing on CD63, a tetraspanin
protein expressed on various cellular membranes, including EVs, we examined
whether a DNA vaccine encoding an Ag fused to CD63 delivered into EVs would
improve vaccine immunogenicity. In vitro transfection with plasmid DNA encoding
an OVA Ag fused to CD63 (pCD63-OVA) produced OVA-carrying EVs. Immunizations with
the purified OVA-carrying EVs primed naive mice to induce OVA-specific CD4+ and
CD8+ T cells, whereas immunization with EVs purified from cells transfected with
control plasmids encoding OVA protein alone or a calnexin-OVA fusion protein
delivered into the endoplasmic reticulum failed to do so. Vaccinating mice with
pCD63-OVA induced potent Ag-specific T cell responses, particularly those from
CD8+ T cells. CD63 delivery into EVs led to better CD8+ T cell responses than
calnexin delivery into the endoplasmic reticulum. When we used a mouse tumor
implantation model to evaluate pCD63-OVA as a therapeutic vaccine, the EV
delivered DNA vaccination significantly inhibited tumor growth compared with the
control DNA vaccinations. These results indicate that EV Ag delivery via DNA
vaccination offers a new strategy for eliciting strong CD8+ T cell responses to
the encoded Ag, making it a potentially useful cancer vaccine.
PMID- 28507030
TI - CCR2 Regulates the Immune Response by Modulating the Interconversion and Function
of Effector and Regulatory T Cells.
AB - Chemokines and chemokine receptors establish a complex network modulating immune
cell migration and localization. These molecules were also suggested to mediate
the differentiation of leukocytes; however, their intrinsic, direct regulation of
lymphocyte fate remained unclear. CCR2 is the main chemokine receptor inducing
macrophage and monocyte recruitment to sites of inflammation, and it is also
expressed on T cells. To assess whether CCR2 directly regulates T cell responses,
we followed the fates of CCR2-/- T cells in T cell-specific inflammatory models.
Our in vitro and in vivo results show that CCR2 intrinsically mediates the
expression of inflammatory T cell cytokines, and its absence on T cells results
in attenuated colitis progression. Moreover, CCR2 deficiency in T cells promoted
a program inducing the accumulation of Foxp3+ regulatory T cells, while
decreasing the levels of Th17 cells in vivo, indicating that CCR2 regulates the
immune response by modulating the effector/regulatory T ratio.
PMID- 28507031
TI - Memory consolidation within the central amygdala is not necessary for modulation
of cerebellar learning.
AB - Amygdala lesions impair, but do not prevent, acquisition of cerebellum-dependent
eyeblink conditioning suggesting that the amygdala modulates cerebellar learning.
Two-factor theories of eyeblink conditioning posit that a fast-developing memory
within the amygdala facilitates slower-developing memory within the cerebellum.
The current study tested this hypothesis by impairing memory consolidation within
the amygdala with inhibition of protein synthesis, transcription, and NMDA
receptors in rats. Rats given infusions of anisomycin or DRB into the central
amygdala (CeA) immediately after each eyeblink conditioning session were severely
impaired in contextual and cued fear conditioning, but were completely unimpaired
in eyeblink conditioning. Rats given the NMDA antagonist ifenprodil into the CeA
before each eyeblink conditioning session also showed impaired fear conditioning,
but no deficit in eyeblink conditioning. The results indicate that memory
formation within the CeA is not necessary for its modulation of cerebellar
learning mechanisms. The CeA may modulate cerebellar learning and retention
through an attentional mechanism that develops within the training sessions.
PMID- 28507033
TI - Response-specific sex difference in the retention of fear extinction.
AB - Fear conditioning studies in rodents allow us to assess vulnerability factors
which might underlie fear-based psychopathology such as post-traumatic stress
disorder (PTSD). Despite PTSD being more prevalent in females than males, very
few fear conditioning studies in rodents have tested females. Our study assessed
fear conditioning and extinction in male and female rats using both fear
potentiated startle and freezing behavior as measures. Rats were trained to fear
cues that predicted the occurrence of shock and then subsequently exposed to an
extinction training procedure where the cue was presented repeatedly in the
absence of shock. Retention of the extinction memory was assessed the next day.
Our results showed that females exhibited less retention of fear extinction, but
only when measured by fear-potentiated startle. Our results highlight the
importance of using multiple indices of fear behavior, particularly when
comparing sexes on measures of extinction learning.
PMID- 28507034
TI - Sleep supports inhibitory operant conditioning memory in Aplysia.
AB - Sleep supports memory consolidation as shown in mammals and invertebrates such as
bees and Drosophila. Here, we show that sleep's memory function is preserved in
Aplysia californica with an even simpler nervous system. Animals performed on an
inhibitory conditioning task ("learning that a food is inedible") three times, at
Training, Retrieval 1, and Retrieval 2, with 17-h intervals between tests.
Compared with Wake animals, remaining awake between Training and Retrieval 1,
Sleep animals with undisturbed post-training sleep, performed significantly
better at Retrieval 1 and 2. Control experiments testing retrieval only after ~34
h, confirmed the consolidating effect of sleep occurring within 17 h after
training.
PMID- 28507032
TI - alpha2* Nicotinic acetylcholine receptors influence hippocampus-dependent
learning and memory in adolescent mice.
AB - The absence of alpha2* nicotinic acetylcholine receptors (nAChRs) in oriens
lacunosum moleculare (OLM) GABAergic interneurons ablate the facilitation of
nicotine-induced hippocampal CA1 long-term potentiation and impair memory. The
current study delineated whether genetic mutations of alpha2* nAChRs
(Chrna2L9'S/L9'S and Chrna2KO) influence hippocampus-dependent learning and
memory and CA1 synaptic plasticity. We substituted a serine for a leucine (L9'S)
in the alpha2 subunit (encoded by the Chrna2 gene) to make a hypersensitive
nAChR. Using a dorsal hippocampus-dependent task of preexposure-dependent
contextual fear conditioning, adolescent hypersensitive Chrna2L9'S/L9'S male mice
exhibited impaired learning and memory. The deficit was rescued by low-dose
nicotine exposure. Electrophysiological studies demonstrated that hypersensitive
alpha2 nAChRs potentiate acetylcholine-induced ion channel flux in oocytes and
acute nicotine-induced facilitation of dorsal/intermediate CA1 hippocampal long
term potentiation in Chrna2L9'S/L9'S mice. Adolescent male mice null for the
alpha2 nAChR subunit exhibited a baseline deficit in learning that was not
reversed by an acute dose of nicotine. These effects were not influenced by
locomotor, sensory or anxiety-related measures. Our results demonstrated that
alpha2* nAChRs influenced hippocampus-dependent learning and memory, as well as
nicotine-facilitated CA1 hippocampal synaptic plasticity.
PMID- 28507035
TI - Long-term sensitization training in Aplysia decreases the excitability of a
decision-making neuron through a sodium-dependent mechanism.
AB - In Aplysia, long-term sensitization (LTS) occurs concurrently with a suppression
of feeding. At the cellular level, the suppression of feeding is accompanied by
decreased excitability of decision-making neuron B51. We examined the
contribution of voltage-gated Na+ and K+ channels to B51 decreased excitability.
In a pharmacologically isolated Na+ channels environment, LTS training
significantly increased B51 firing threshold, compared with untrained controls.
Conversely, in a pharmacologically isolated K+ channels environment, no
differences were observed between trained and untrained animals in either
amplitude or area of B51 K+-dependent depolarizations. These findings suggest
that Na+ channels contribute to the decrease in B51 excitability induced by LTS
training.
PMID- 28507036
TI - Medial prefrontal cortex and dorsomedial striatum are necessary for the trial
unique, delayed nonmatching-to-location (TUNL) task in rats: role of NMDA
receptors.
AB - The trial-unique, delayed nonmatching-to-location (TUNL) task is a recently
developed behavioral task that measures spatial working memory and a form of
pattern separation in touchscreen-equipped operant conditioning chambers. Limited
information exists regarding the neurotransmitters and neural substrates involved
in the task. The present experiments tested the effects of systemic and
intracranial injections of NMDA receptor antagonists on the TUNL task. After
training, male Long Evans rats systemically injected with the competitive NMDA
receptor antagonist CPP (10 mg/kg) had impaired accuracy regardless of the degree
of stimuli separation or length of delay between the sample and test phases.
Injections of Ro 25-6981 (6 or 10 mg/kg), an antagonist selective for GluN2B
subunit-containing NMDA receptors, did not affect accuracy on the task. Direct
infusion of the competitive NMDA receptor antagonist AP5 into mPFC or dmSTR
reduced overall accuracy on the TUNL task. These results demonstrate that TUNL
task performance depends on NMDA receptors within the mPFC and dmSTR.
PMID- 28507037
TI - Systemic Activation of NRF2 Alleviates Lethal Autoimmune Inflammation in Scurfy
Mice.
AB - The transcription factor NRF2 (nuclear factor [erythroid-derived 2]-like 2) plays
crucial roles in the defense mechanisms against oxidative stress and mediates
anti-inflammatory actions under various pathological conditions. Recent studies
showed that the dysfunction of regulatory T cells (Tregs) is directly linked to
the initiation and progression of various autoimmune diseases. To determine the
Treg-independent impact of NRF2 activation on autoimmune inflammation, we
examined scurfy (Sf) mice, which are deficient in Tregs and succumb to severe
multiorgan inflammation by 4 weeks of age. We found that systemic activation of
NRF2 by Keap1 (Kelch-like ECH-associated protein 1) knockdown ameliorated tissue
inflammation and lethality in Sf mice. Activated T cells and their cytokine
production were accordingly decreased by Keap1 knockdown. In contrast, NRF2
activation through cell lineage-specific Keap1 disruption (i.e., in T cells,
myeloid cells, and dendritic cells) achieved only partial or no improvement in
the inflammatory status of Sf mice. Our results indicate that systemic activation
of NRF2 suppresses effector T cell activities independently of Tregs and that
NRF2 activation in multiple cell lineages appears to be required for sufficient
anti-inflammatory effects. This study emphasizes the possible therapeutic
application of NRF2 inducers in autoimmune diseases that are accompanied by Treg
dysfunction.
PMID- 28507038
TI - High-affinity pan-specific monoclonal antibodies that target cysteinyl
leukotrienes and show efficacy in an acute model of colitis.
AB - Cysteinyl leukotrienes (CysLTs) are a small family of biological signaling lipids
produced by active leukocytes that contribute to diverse inflammatory disease
states as a consequence of their engagement with dedicated G protein-coupled
receptors. Immunization of mice with a CysLT-modified hapten carrier protein
yielded novel monoclonal antibodies that display variable binding affinity to
CysLTs. Solution binding assays indicated differing specificities among the
antibodies tested, with antibody 10G4 displaying a preference for leukotriene C4
(LTC4). X-ray crystallography of a humanized 10G4 Fab fragment in complex with
LTC4 revealed that binding induces a hook-like conformation within the
hydrocarbon tail of the lipid arachidonic acid moiety. Specific hydrogen bonding
to the LTC4 carboxylate groups further stabilized the complex, while a water
molecule mediated a hydrogen bond network that connected the N-terminal arm of l
glutathione to both the arachidonyl carboxylate of LTC4 and the antibody heavy
chain. Prophylactic administration of two anti-CysLT antibodies in mice followed
by challenge with LTC4 demonstrated their in vivo efficacy against acute
inflammation in a vascular permeability model. 10G4 ameliorated the effects of
acute dextran sulfate sodium-induced colitis, suggesting that anti-CysLT
antibodies could provide a therapeutic benefit in the treatment of inflammatory
diseases.
PMID- 28507041
TI - Publisher's Note - Relating to the retraction of: Oxidative stress inactivates
VEGF survival signaling in retinal endothelial cells via PI 3-kinase tyrosine
nitration. Azza B. El-Remessy, Manuela Bartoli, Danial H. Platt, David Fulton,
Ruth B. Caldwell. J. Cell Sci. doi:10.1242/jcs.195966.
PMID- 28507039
TI - Do Aspirin and Other NSAIDs Confer a Survival Benefit in Men Diagnosed with
Prostate Cancer? A Pooled Analysis of NIH-AARP and PLCO Cohorts.
AB - Prostate cancer is one of the leading causes of cancer-related death in U.S. men.
There is an unmet need to identify modifiable risk factors for prostate cancer
survival. Experimental studies have suggested that nonsteroidal anti-inflammatory
drugs (NSAIDs) may improve prostate cancer survival through antithrombotic and
anti-inflammation mechanisms. Results from previous observational studies have
been equivocal, and few have assessed whether an etiologically relevant time
window of exposure exists. We sampled incident prostate cancer cases from two
large U.S. prospective cohorts, NIH-AARP Diet and Health Study and PLCO Cancer
Screening Trial, to investigate whether pre- and postdiagnostic aspirin and non
aspirin NSAID use were associated with prostate cancer-specific and all-cause
mortality. Cox proportional hazards regression models estimated hazard ratios
(HRs) and 95% confidence intervals (CIs). Study-specific results were meta
analyzed using fixed-effects models. Pre- and postdiagnostic aspirin or non
aspirin NSAID use were not statistically significantly associated with prostate
cancer-specific mortality. However, occasional (less than daily) and daily
aspirin users five years or more before prostate cancer diagnosis had 18% (HR =
0.82; 95% CI = 0.75-0.90) and 15% (HR = 0.85; 95% CI = 0.77-0.94) reduced all
cause mortality versus nonusers. Similarly, postdiagnostic occasional and daily
aspirin use were associated with 17% (HR = 0.83; 95% CI=0.72-0.95) and 25% (HR =
0.75; 95% CI = 0.66-0.86) reduced all-cause mortality, independent of
prediagnostic aspirin use. This study suggests that aspirin or non-aspirin NSAIDs
are not associated with prostate cancer survival. However, aspirin use both
before and after prostate cancer diagnosis was associated with longer overall
survival, highlighting the importance of comorbidity prevention among prostate
cancer survivors. Cancer Prev Res; 10(7); 410-20. (c)2017 AACR.
PMID- 28507049
TI - Models in Translational Oncology: A Public Resource Database for Preclinical
Cancer Research.
AB - The devastating diseases of human cancer are mimicked in basic and translational
cancer research by a steadily increasing number of tumor models, a situation
requiring a platform with standardized reports to share model data. Models in
Translational Oncology (MiTO) database was developed as a unique Web platform
aiming for a comprehensive overview of preclinical models covering genetically
engineered organisms, models of transplantation, chemical/physical induction, or
spontaneous development, reviewed here. MiTO serves data entry for metastasis
profiles and interventions. Moreover, cell lines and animal lines including tool
strains can be recorded. Hyperlinks for connection with other databases and file
uploads as supplementary information are supported. Several communication tools
are offered to facilitate exchange of information. Notably, intellectual property
can be protected prior to publication by inventor-defined accessibility of any
given model. Data recall is via a highly configurable keyword search. Genome
editing is expected to result in changes of the spectrum of model organisms, a
reason to open MiTO for species-independent data. Registered users may deposit
own model fact sheets (FS). MiTO experts check them for plausibility.
Independently, manually curated FS are provided to principle investigators for
revision and publication. Importantly, noneditable versions of reviewed FS can be
cited in peer-reviewed journals. Cancer Res; 77(10); 2557-63. (c)2017 AACR.
PMID- 28507051
TI - Correction: Tumor-Intrinsic PD-L1 Signals Regulate Cell Growth, Pathogenesis, and
Autophagy in Ovarian Cancer and Melanoma.
PMID- 28507052
TI - Correction: Pulsed High-Intensity Focused Ultrasound Enhances Delivery of
Doxorubicin in a Preclinical Model of Pancreatic Cancer.
PMID- 28507053
TI - Correction: Metastatic Progression of Prostate Cancer Is Mediated by Autonomous
Binding of Galectin-4-O-Glycan to Cancer Cells.
PMID- 28507050
TI - Tumor Dormancy and Relapse: From a Natural Byproduct of Evolution to a Disease
State.
AB - Species evolve by mutations and epigenetic changes acting on individuals in a
population; tumors evolve by similar mechanisms at a cellular level in a tissue.
This article reviews growing evidence about tumor dormancy and suggests that (i)
cellular malignancy is a natural byproduct of evolutionary mechanisms, such as
gene mutations and epigenetic modifications, which is manifested in the form of
tumor dormancy in healthy individuals as well as in cancer survivors; (ii) cancer
metastasis could be an early dissemination event that could occur during
malignant dormancy even before primary cancer is clinically detectable; and (iii)
chronic inflammation is a key factor in awakening dormant malignant cells at the
primary site, leading to primary cancer development, and at distant sites,
leading to advanced stage diseases. On the basis of this evidence, it is
reasonable to propose that we are all cancer survivors rather than cancer-free
individuals because of harboring dormant malignant cells in our organs. A better
understanding of local and metastatic tumor dormancy could lead to novel cancer
therapeutics for the prevention of cancer. Cancer Res; 77(10); 2564-9. (c)2017
AACR.
PMID- 28507055
TI - Adhesion and friction of the smooth attachment system of the cockroach
Gromphadorhina portentosa and the influence of the application of fluid
adhesives.
AB - Two different measurement techniques were applied to study the attachment of the
smooth foot pads of the Madagascar hissing cockroach Gromphadorhina portentosa
The attachment of the non-manipulated adhesive organs was compared with that of
manipulated ones (depletion or substitution by artificial secretions). From
measurements of the friction on a centrifuge, it can be concluded that on
nanorough surfaces, the insect appears to benefit from employing emulsions
instead of pure oils to avoid excessive friction. Measurements performed with a
nanotribometer on single attachment organs showed that, in the non-manipulated
euplantulae, friction was clearly increased in the push direction, whereas the
arolium of the fore tarsus showed higher friction in the pull direction. The
surface of the euplantulae shows an imbricate appearance, whereupon the ledges
face distally, which might contribute to the observed frictional anisotropy in
the push direction. Upon depletion of the tarsal adhesion-mediating secretion or
its replacement by oily fluids, in several cases, the anisotropic effect of the
euplantula disappeared due to the decrease of friction forces in push-direction.
In the euplantulae, adhesion was one to two orders of magnitude lower than
friction. Whereas the tenacity was slightly decreased with depleted secretion, it
was considerably increased after artificial application of oily liquids. In terms
of adhesion, it is concluded that the semi-solid consistence of the natural
adhesion-mediating secretion facilitates the detachment of the tarsus during
locomotion. In terms of friction, on smooth to nanorough surfaces, the insects
appear to benefit from employing emulsions instead of pure oils to avoid
excessive friction forces, whereas on rougher surfaces the tarsal fluid rather
functions in improving surface contact by keeping the cuticle compliable and
compensating surface asperities of the substratum.
PMID- 28507056
TI - Parallel in vivo monitoring of pH in gill capillaries and muscles of fishes using
microencapsulated biomarkers.
AB - Tracking physiological parameters in different organs within the same organism
simultaneously and in real time can provide an outstanding representation of the
organism's physiological status. The state-of-the-art technique of using
encapsulated fluorescent molecular probes (microencapsulated biomarkers) is a
unique tool that can serve as a platform for the development of new methods to
obtain in vivo physiological measurements and is applicable to a broad range of
organisms. Here, we describe a novel technique to monitor the pH of blood inside
the gill capillaries and interstitial fluid of muscles by using microencapsulated
biomarkers in a zebrafish model. The functionality of the proposed technique is
shown by the identification of acidification under anesthesia-induced coma and
after death. The pH in muscles reacts to hypoxia faster than that in the gill
bloodstream, which makes both parameters applicable as markers of either local or
bodily reactions.
PMID- 28507054
TI - Glutamine Transporters Are Targets of Multiple Oncogenic Signaling Pathways in
Prostate Cancer.
AB - Despite the known importance of androgen receptor (AR) signaling in prostate
cancer, the processes downstream of AR that drive disease development and
progression remain poorly understood. This knowledge gap has thus limited the
ability to treat cancer. Here, it is demonstrated that androgens increase the
metabolism of glutamine in prostate cancer cells. This metabolism was required
for maximal cell growth under conditions of serum starvation. Mechanistically, AR
signaling promoted glutamine metabolism by increasing the expression of the
glutamine transporters SLC1A4 and SLC1A5, genes commonly overexpressed in
prostate cancer. Correspondingly, gene expression signatures of AR activity
correlated with SLC1A4 and SLC1A5 mRNA levels in clinical cohorts. Interestingly,
MYC, a canonical oncogene in prostate cancer and previously described master
regulator of glutamine metabolism, was only a context-dependent regulator of
SLC1A4 and SLC1A5 levels, being unable to regulate either transporter in PTEN
wild-type cells. In contrast, rapamycin was able to decrease the androgen
mediated expression of SLC1A4 and SLC1A5 independent of PTEN status, indicating
that mTOR complex 1 (mTORC1) was needed for maximal AR-mediated glutamine uptake
and prostate cancer cell growth. Taken together, these data indicate that three
well-established oncogenic drivers (AR, MYC, and mTOR) function by converging to
collectively increase the expression of glutamine transporters, thereby promoting
glutamine uptake and subsequent prostate cancer cell growth.Implications: AR,
MYC, and mTOR converge to increase glutamine uptake and metabolism in prostate
cancer through increasing the levels of glutamine transporters. Mol Cancer Res;
15(8); 1017-28. (c)2017 AACR.
PMID- 28507057
TI - Benefit of Ezetimibe Added to Simvastatin in Reduced Kidney Function.
AB - Efficacy of statin-based therapies in reducing cardiovascular mortality in
individuals with CKD seems to diminish as eGFR declines. The strongest evidence
supporting the cardiovascular benefit of statins in individuals with CKD was
shown with ezetimibe plus simvastatin versus placebo. However, whether
combination therapy or statin alone resulted in cardiovascular benefit is
uncertain. Therefore, we estimated GFR in 18,015 individuals from the IMPROVE-IT
(ezetimibe plus simvastatin versus simvastatin alone in individuals with
cardiovascular disease and creatinine clearance >30 ml/min) and examined post hoc
the relationship of eGFR with end points across treatment arms. For the primary
end point of cardiovascular death, major coronary event, or nonfatal stroke, the
relative risk reduction of combination therapy compared with monotherapy differed
by eGFR (P=0.04). The difference in treatment effect was observed at eGFR<=75
ml/min per 1.73 m2 and most apparent at levels <=60 ml/min per 1.73 m2 Compared
with individuals receiving monotherapy, individuals receiving combination therapy
with a baseline eGFR of 60 ml/min per 1.73 m2 experienced a 12% risk reduction
(hazard ratio [HR], 0.88; 95% confidence interval [95% CI], 0.82 to 0.95); those
with a baseline eGFR of 45 ml/min per 1.73 m2 had a 13% risk reduction (HR, 0.87;
95% CI, 0.78 to 0.98). In stabilized individuals within 10 days of acute coronary
syndrome, combination therapy seemed to be more effective than monotherapy in
individuals with moderately reduced eGFR (30-60 ml/min per 1.73 m2). Further
studies examining potential benefits of combination lipid-lowering therapy in
individuals with CKD are needed.
PMID- 28507058
TI - Hepatocyte Nuclear Factor-1beta Regulates Urinary Concentration and Response to
Hypertonicity.
AB - The transcription factor hepatocyte nuclear factor-1beta (HNF-1beta) is essential
for normal kidney development and function. Inactivation of HNF-1beta in mouse
kidney tubules leads to early-onset cyst formation and postnatal lethality. Here,
we used Pkhd1/Cre mice to delete HNF-1beta specifically in renal collecting ducts
(CDs). CD-specific HNF-1beta mutant mice survived long term and developed slowly
progressive cystic kidney disease, renal fibrosis, and hydronephrosis. Compared
with wild-type littermates, HNF-1beta mutant mice exhibited polyuria and
polydipsia. Before the development of significant renal structural abnormalities,
mutant mice exhibited low urine osmolality at baseline and after water
restriction and administration of desmopressin. However, mutant and wild-type
mice had similar plasma vasopressin and solute excretion levels. HNF-1beta mutant
kidneys showed increased expression of aquaporin-2 mRNA but mislocalized
expression of aquaporin-2 protein in the cytoplasm of CD cells. Mutant kidneys
also had decreased expression of the UT-A urea transporter and collectrin, which
is involved in apical membrane vesicle trafficking. Treatment of HNF-1beta mutant
mIMCD3 cells with hypertonic NaCl inhibited the induction of osmoregulated genes,
including Nr1h4, which encodes the transcription factor FXR that is required for
maximal urinary concentration. Chromatin immunoprecipitation and sequencing
experiments revealed HNF-1beta binding to the Nr1h4 promoter in wild-type
kidneys, and immunoblot analysis revealed downregulated expression of FXR in HNF
1beta mutant kidneys. These findings reveal a novel role of HNF-1beta in
osmoregulation and identify multiple mechanisms, whereby mutations of HNF-1beta
produce defects in urinary concentration.
PMID- 28507059
TI - Change in Physical Activity and Sitting Time After Myocardial Infarction and
Mortality Among Postmenopausal Women in the Women's Health Initiative
Observational Study.
AB - BACKGROUND: How physical activity (PA) and sitting time may change after first
myocardial infarction (MI) and the association with mortality in postmenopausal
women is unknown. METHODS AND RESULTS: Participants included postmenopausal women
in the Women's Health Initiative-Observational Study, aged 50 to 79 years who
experienced a clinical MI during the study. This analysis included 856 women who
had adequate data on PA exposure and 533 women for sitting time exposures.
Sitting time was self-reported at baseline, year 3, and year 6. Self-reported PA
was reported at baseline through year 8. Change in PA and sitting time were
calculated as the difference between the cumulative average immediately following
MI and the cumulative average immediately preceding MI. The 4 categories of
change were: maintained low, decreased, increased, and maintained high. The cut
points were >=7.5 metabolic equivalent of task hours/week versus <7.5 metabolic
equivalent of task hours/week for PA and >=8 h/day versus <8 h/day for sitting
time. Cox proportional hazard models estimated hazard ratios and 95% CIs for all
cause, coronary heart disease, and cardiovascular disease mortality. Compared
with women who maintained low PA (referent), the risk of all-cause mortality was:
0.54 (0.34-0.86) for increased PA and 0.52 (0.36-0.73) for maintained high PA.
Women who had pre-MI levels of sitting time <8 h/day, every 1 h/day increase in
sitting time was associated with a 9% increased risk (hazard ratio=1.09, 95% CI:
1.01, 1.19) of all-cause mortality. CONCLUSIONS: Meeting the recommended PA
guidelines pre- and post-MI may have a protective role against mortality in
postmenopausal women.
PMID- 28507060
TI - Alogliptin, a Dipeptidyl Peptidase-4 Inhibitor, Alleviates Atrial Remodeling and
Improves Mitochondrial Function and Biogenesis in Diabetic Rabbits.
AB - BACKGROUND: There is increasing evidence implicating atrial mitochondrial
dysfunction in the pathogenesis of atrial fibrillation. In this study, we
explored whether alogliptin, a dipeptidyl peptidase-4 inhibitor, can prevent
mitochondrial dysfunction and atrial remodeling in a diabetic rabbit model.
METHODS AND RESULTS: A total of 90 rabbits were randomized into 3 groups as
follows: control group (n=30), alloxan-induced diabetes mellitus group (n=30),
and alogliptin-treated (12.5 mg/kg per day for 8 weeks) diabetes mellitus group
(n=30). Echocardiographic and hemodynamic assessments were performed in vivo. The
serum concentrations of glucagon-like peptide-1, insulin, and inflammatory and
oxidative stress markers were measured. Electrophysiological properties of
Langendorff-perfused rabbit hearts were assessed. Mitochondrial morphology,
respiratory function, membrane potential, and reactive oxygen species generation
rate were assessed. The protein expression of transforming growth factor beta1,
nuclear factor kappaB p65, and mitochondrial biogenesis-related proteins were
measured by Western blot analysis. Diabetic rabbits exhibited left ventricular
hypertrophy and left atrial dilation without obvious hemodynamic abnormalities,
and all of these changes were attenuated by alogliptin. Compared with the control
group, higher atrial fibrillation inducibility in the diabetes mellitus group was
observed, and markedly reduced by alogliptin. Alogliptin decreased mitochondrial
reactive oxygen species production rate, prevented mitochondrial membrane
depolarization, and alleviated mitochondrial swelling in diabetic rabbits. It
also improved mitochondrial biogenesis by peroxisome proliferator-activated
receptor-gamma coactivator 1alpha/nuclear respiratory factor-1/mitochondrial
transcription factor A signaling regulated by adiponectin/AMP-activated protein
kinase. CONCLUSIONS: Dipeptidyl peptidase-4 inhibitors can prevent atrial
fibrillation by reversing electrophysiological abnormalities, improving
mitochondrial function, and promoting mitochondrial biogenesis.
PMID- 28507061
TI - RNF8 mediates histone H3 ubiquitylation and promotes glycolysis and
tumorigenesis.
AB - Disassembly of nucleosomes in which genomic DNA is packaged with histone
regulates gene expression. However, the mechanisms underlying nucleosome
disassembly for gene expression remain elusive. We show here that epidermal
growth factor receptor activation results in the binding of the RNF8 forkhead
associated domain to pyruvate kinase M2-phosphorylated histone H3-T11, leading to
K48-linked polyubiquitylation of histone H3 at K4 and subsequent proteasome
dependent protein degradation. In addition, H3 polyubiquitylation induces histone
dissociation from chromatin, nucleosome disassembly, and binding of RNA
polymerase II to MYC and CCND1 promoter regions for transcription. RNF8-mediated
histone H3 polyubiquitylation promotes tumor cell glycolysis and proliferation
and brain tumorigenesis. Our findings uncover the role of RNF8-mediated histone
H3 polyubiquitylation in the regulation of histone H3 stability and chromatin
modification, paving the way to gene expression regulation and tumorigenesis.
PMID- 28507062
TI - Interleukin 4 promotes the development of ex-Foxp3 Th2 cells during immunity to
intestinal helminths.
AB - Immunity to intestinal helminth infections requires the rapid activation of T
helper 2 cells (Th2 cells). However, simultaneous expansion of CD4+Foxp3+
regulatory T cells (T reg cells) impedes protective responses, resulting in
chronic infections. The ratio between T reg and effector T cells can therefore
determine the outcome of infection. The redifferentiation of T reg cells into Th
cells has been identified in hyperinflammatory diseases. In this study, we asked
whether ex-T reg Th2 cells develop and contribute to type-2 immunity. Using
multigene reporter and fate-reporter systems, we demonstrate that a significant
proportion of Th2 cells derive from Foxp3+ cells after Heligmosomoides polygyrus
infection and airway allergy. Ex-Foxp3 Th2 cells exhibit characteristic Th2
effector functions and provide immunity to H. polygyrus Through selective
deletion of Il4ra on Foxp3+ cells, we further demonstrate IL-4 is required for
the development of ex-Foxp3 Th2 cells. Collectively, our findings indicate that
converting T reg cells into Th2 cells could concomitantly enhance Th2 cells and
limit T reg cell-mediated suppression.
PMID- 28507064
TI - Tumor Necrosis Factor Receptor-Associated Factor 6 (TRAF6) Mediates
Ubiquitination-Dependent STAT3 Activation upon Salmonella enterica Serovar
Typhimurium Infection.
AB - Salmonella enterica serovar Typhimurium can inject effector proteins into host
cells via type III secretion systems (T3SSs). These effector proteins modulate a
variety of host transcriptional responses to facilitate bacterial growth and
survival. Here we show that infection of host cells with S Typhimurium
specifically induces the ubiquitination of tumor necrosis factor receptor
associated factor 6 (TRAF6). This TRAF6 ubiquitination is triggered by the
Salmonella pathogenicity island 1 (SPI-1) T3SS effectors SopB and SopE2. We also
demonstrate that TRAF6 is involved in the SopB/SopE2-induced phosphorylation of
signal transducer and activator of transcription 3 (STAT3), a signaling event
conducive to the intracellular growth of S Typhimurium. Specifically, TRAF6
mediates lysine-63 ubiquitination within the Src homology 2 (SH2) domain of
STAT3, which is an essential step for STAT3 membrane recruitment and subsequent
phosphorylation in response to S Typhimurium infection. TRAF6 ubiquitination
participates in STAT3 phosphorylation rather than serving as only a hallmark of
E3 ubiquitin ligase activation. Our results reveal a novel strategy in which S
Typhimurium T3SS effectors broaden their functions through the activation of host
proteins in a ubiquitination-dependent manner to manipulate host cells into
becoming a Salmonella-friendly zone.
PMID- 28507063
TI - The Mycobacterium tuberculosis MmpL11 Cell Wall Lipid Transporter Is Important
for Biofilm Formation, Intracellular Growth, and Nonreplicating Persistence.
AB - The mycobacterial cell wall is crucial to the host-pathogen interface, because it
provides a barrier against antibiotics and the host immune response. In addition,
cell wall lipids are mycobacterial virulence factors. The mycobacterial membrane
protein large (MmpL) proteins are cell wall lipid transporters that are important
for basic mycobacterial physiology and Mycobacterium tuberculosis pathogenesis.
MmpL3 and MmpL11 are conserved across pathogenic and nonpathogenic mycobacteria,
a feature consistent with an important role in the basic physiology of the
bacterium. MmpL3 is essential and transports trehalose monomycolate to the
mycobacterial surface. In this report, we characterize the role of MmpL11 in M.
tuberculosis. M. tuberculosismmpL11 mutants have altered biofilms associated with
lower levels of mycolic acid wax ester and long-chain triacylglycerols than those
for wild-type bacteria. While the growth rate of the mmpL11 mutant is similar to
that of wild-type M. tuberculosis in macrophages, the mutant exhibits impaired
survival in an in vitro granuloma model. Finally, we show that the survival or
recovery of the mmpL11 mutant is impaired when it is incubated under conditions
of nutrient and oxygen starvation. Our results suggest that MmpL11 and its cell
wall lipid substrates are important for survival in the context of adaptive
immune pressure and for nonreplicating persistence, both of which are critically
important aspects of M. tuberculosis pathogenicity.
PMID- 28507065
TI - Mutations in the beta-Subunit of the RNA Polymerase Impair the Surface-Associated
Motility and Virulence of Acinetobacter baumannii.
AB - Acinetobacter baumannii is a major cause of antibiotic-resistant nosocomial
infections worldwide. In this study, several rifampin-resistant spontaneous
mutants obtained from the A. baumannii ATCC 17978 strain that differed in their
point mutations in the rpoB gene, encoding the beta-subunit of the RNA
polymerase, were isolated. All the mutants harboring amino acid substitutions in
position 522 or 540 of the RpoB protein were impaired in surface-associated
motility and had attenuated virulence in the fertility model of Caenorhabditis
elegans The transcriptional profile of these mutants included six downregulated
genes encoding proteins homologous to transporters and metabolic enzymes
widespread among A. baumannii clinical isolates. The construction of knockout
mutants in each of the six downregulated genes revealed a significant reduction
in the surface-associated motility and virulence of four of them in the A.
baumannii ATCC 17978 strain, as well as in the virulent clinical isolate MAR002.
Taken together, our results provide strong evidence of the connection between
motility and virulence in this multiresistant nosocomial pathogen.
PMID- 28507066
TI - Microbiomes of Site-Specific Dental Plaques from Children with Different Caries
Status.
AB - The oral microbiota associated with the initiation and progression of dental
caries has yet to be fully characterized. The Human Oral Microbe Identification
Using Next-Generation Sequencing (HOMINGS) approach was used to analyze the
microbiomes of site-specific supragingival dental plaques from children with
different caries status. Fifty-five children (2 to 7 years of age) were assessed
at baseline and at 12 months and grouped as caries free (CF), caries active with
enamel lesions (CAE), and caries active with dentin carious lesions (CA). Plaque
samples from caries-free tooth surfaces (PF) and from enamel carious lesions (PE)
and dentin carious lesions (PD) were collected. 16S community profiles were
obtained by HOMINGS, and 408 bacterial species and 84 genus probes were assigned.
Plaque bacterial communities showed temporal stability, as there was no
significant difference in beta diversity values between the baseline and 12-month
samples. Irrespective of collection time points, the microbiomes of healthy tooth
surfaces differed substantially from those found during caries activity. All
pairwise comparisons of beta diversity values between groups were significantly
different (P < 0.05), except for comparisons between the CA-PF, CAE-PE, and CA-PE
groups. Streptococcus genus probe 4 and Neisseria genus probe 2 were the most
frequently detected taxa across the plaque groups, followed by Streptococcus
sanguinis, which was highly abundant in CF-PF. Well-known acidogenic/aciduric
species such as Streptococcus mutans, Scardovia wiggsiae, Parascardovia
denticolens, and Lactobacillus salivarius were found almost exclusively in CA-PD.
The microbiomes of supragingival dental plaque differ substantially among tooth
surfaces and children of different caries activities. In support of the
ecological nature of caries etiology, a steady transition in community species
composition was observed with disease progression.
PMID- 28507069
TI - SaeRS Is Responsive to Cellular Respiratory Status and Regulates Fermentative
Biofilm Formation in Staphylococcus aureus.
AB - Biofilms are multicellular communities of microorganisms living as a quorum
rather than as individual cells. The bacterial human pathogen Staphylococcus
aureus uses oxygen as a terminal electron acceptor during respiration. Infected
human tissues are hypoxic or anoxic. We recently reported that impaired
respiration elicits a programmed cell lysis (PCL) phenomenon in S. aureus leading
to the release of cellular polymers that are utilized to form biofilms. PCL is
dependent upon the AtlA murein hydrolase and is regulated, in part, by the SrrAB
two-component regulatory system (TCRS). In the current study, we report that the
SaeRS TCRS also governs fermentative biofilm formation by positively influencing
AtlA activity. The SaeRS-modulated factor fibronectin-binding protein A (FnBPA)
also contributed to the fermentative biofilm formation phenotype. SaeRS-dependent
biofilm formation occurred in response to changes in cellular respiratory status.
Genetic evidence presented suggests that a high cellular titer of phosphorylated
SaeR is required for biofilm formation. Epistasis analyses found that SaeRS and
SrrAB influence biofilm formation independently of one another. Analyses using a
mouse model of orthopedic implant-associated biofilm formation found that both
SaeRS and SrrAB govern host colonization. Of these two TCRSs, SrrAB was the
dominant system driving biofilm formation in vivo We propose a model wherein
impaired cellular respiration stimulates SaeRS via an as yet undefined signal
molecule(s), resulting in increasing expression of AtlA and FnBPA and biofilm
formation.
PMID- 28507067
TI - Global Transcriptional Response to Organic Hydroperoxide and the Role of OhrR in
the Control of Virulence Traits in Chromobacterium violaceum.
AB - A major pathway for the detoxification of organic hydroperoxides, such as cumene
hydroperoxide (CHP), involves the MarR family transcriptional regulator OhrR and
the peroxidase OhrA. However, the effect of these peroxides on the global
transcriptome and the contribution of the OhrA/OhrR system to bacterial virulence
remain poorly explored. Here, we analyzed the transcriptome profiles of
Chromobacterium violaceum exposed to CHP and after the deletion of ohrR, and we
show that OhrR controls the virulence of this human opportunistic pathogen. DNA
microarray and Northern blot analyses of CHP-treated cells revealed the
upregulation of genes related to the detoxification of peroxides (antioxidant
enzymes and thiol-reducing systems), the degradation of the aromatic moiety of
CHP (oxygenases), and protection against other secondary stresses (DNA repair,
heat shock, iron limitation, and nitrogen starvation responses). Furthermore, we
identified two upregulated genes (ohrA and a putative diguanylate cyclase with a
GGDEF domain for cyclic di-GMP [c-di-GMP] synthesis) and three downregulated
genes (hemolysin, chitinase, and collagenase) in the ohrR mutant by transcriptome
analysis. Importantly, we show that OhrR directly repressed the expression of the
putative diguanylate cyclase. Using a mouse infection model, we demonstrate that
the ohrR mutant was attenuated for virulence and showed a decreased bacterial
burden in the liver. Moreover, an ohrR-diguanylate cyclase double mutant
displayed the same virulence as the wild-type strain. In conclusion, we have
defined the transcriptional response to CHP, identified potential virulence
factors such as diguanylate cyclase as members of the OhrR regulon, and shown
that C. violaceum uses the transcriptional regulator OhrR to modulate its
virulence.
PMID- 28507068
TI - Genome-Wide Survey of Pseudomonas aeruginosa PA14 Reveals a Role for the
Glyoxylate Pathway and Extracellular Proteases in the Utilization of Mucin.
AB - Chronic airway infections by the opportunistic pathogen Pseudomonas aeruginosa
are a major cause of mortality in cystic fibrosis (CF) patients. Although this
bacterium has been extensively studied for its virulence determinants, biofilm
growth, and immune evasion mechanisms, comparatively little is known about the
nutrient sources that sustain its growth in vivo Respiratory mucins represent a
potentially abundant bioavailable nutrient source, although we have recently
shown that canonical pathogens inefficiently use these host glycoproteins as a
growth substrate. However, given that P. aeruginosa, particularly in its biofilm
mode of growth, is thought to grow slowly in vivo, the inefficient use of mucin
glycoproteins may be relevant to its persistence within the CF airways. To this
end, we used whole-genome fitness analysis, combining transposon mutagenesis with
high-throughput sequencing, to identify genetic determinants required for P.
aeruginosa growth using intact purified mucins as a sole carbon source. Our
analysis reveals a biphasic growth phenotype, during which the glyoxylate pathway
and amino acid biosynthetic machinery are required for mucin utilization.
Secondary analyses confirmed the simultaneous liberation and consumption of
acetate during mucin degradation and revealed a central role for the
extracellular proteases LasB and AprA. Together, these studies describe a
molecular basis for mucin-based nutrient acquisition by P. aeruginosa and reveal
a host-pathogen dynamic that may contribute to its persistence within the CF
airways.
PMID- 28507070
TI - Limited Colonization Undermined by Inadequate Early Immune Responses Defines the
Dynamics of Decidual Listeriosis.
AB - The bacterial pathogen Listeria monocytogenes causes foodborne systemic disease
in pregnant women, which can lead to preterm labor, stillbirth, or severe
neonatal disease. Colonization of the maternal decidua appears to be an initial
step in the maternal component of the disease as well as bacterial transmission
to the placenta and fetus. Host-pathogen interactions in the decidua during this
early stage of infection remain poorly understood. Here, we assessed the dynamics
of L. monocytogenes infection in primary human decidual organ cultures and in the
murine decidua in vivo A high inoculum was necessary to infect both human and
mouse deciduas, and the data support the existence of a barrier to initial
colonization of the murine decidua. If successful, however, colonization in both
species was followed by significant bacterial expansion associated with an
inability of the decidua to mount appropriate innate cellular immune responses.
The innate immune deficits included the failure of bacterial foci to attract
macrophages and NK cells, cell types known to be important for early defenses
against L. monocytogenes in the spleen, as well as a decrease in the tissue
density of inflammatory Ly6Chi monocytes in vivo These results suggest that the
infectivity of the decidua is not the result of an enhanced recruitment of L.
monocytogenes to the gestational uterus but rather is due to compromised local
innate cellular immune responses.
PMID- 28507072
TI - Recruitment of Neutrophils Mediated by Vgamma2 gammadelta T Cells Deteriorates
Liver Fibrosis Induced by Schistosoma japonicum Infection in C57BL/6 Mice.
AB - Conventional adaptive T cell responses contribute to the pathogenesis of
Schistosoma japonicum infection, leading to liver fibrosis. However, the role of
gamma-delta (gammadelta) T cells in this disease is less clear. gammadelta T
cells are known to secrete interleukin-17 (IL-17) in response to infection,
exerting either protective or pathogenic functions. In the present study, mice
infected with S. japonicum are used to characterize the role of gammadelta T
cells. Combined with the infection of S. japonicum, an extremely significant
increase in the percentage of neutrophils in the CD45+ cells was detected (from
approximately 2.45% to 46.10% in blood and from 0.18% to 7.34% in spleen).
Further analysis identified two different gammadelta T cell subsets that have
different functions in the formation of granulomas in S. japonicum-infected mice.
The Vgamma1 T cells secrete gamma interferon (IFN-gamma) only, while the Vgamma2
T cells secrete both IL-17A and IFN-gamma. Both subtypes lose the ability to
secrete cytokine during the late stage of infection (12 weeks postinfection).
When we depleted the Vgamma2 T cells in infected mice, the percentage of
neutrophils in blood and spleen decreased significantly, the liver fibrosis in
the granulomas was reduced, and the level of IL-17A in the serum decreased (P <
0.05). These results suggest that during S. japonicum infection, Vgamma2 T cells
can recruit neutrophils and aggravate liver fibrosis by secreting IL-17A. This is
the first report that a subset of gammadelta T cells plays a partial role in the
pathological process of schistosome infection.
PMID- 28507074
TI - British Thoracic Society Oxygen Guidelines: another clinical brick in the wall.
PMID- 28507071
TI - Characterization of the Protein Tyrosine Phosphatase LmPRL-1 Secreted by
Leishmania major via the Exosome Pathway.
AB - Similar to other intracellular pathogens, Leishmania parasites are known to evade
the antimicrobial effector functions of host immune cells. To date, however, only
a few virulence factors have been described for Leishmania major, one of the
causative agents of cutaneous leishmaniasis. Here, we have characterized the
expression and function of an L. major phosphatase, which we termed LmPRL-1. This
enzyme shows a strong structural similarity to the human phosphatases of
regenerating liver (PRL-1, -2, and -3) that regulate the proliferation,
differentiation, and motility of cells. The biochemical characterization of the
L. major phosphatase revealed that the enzyme is redox sensitive. When analyzing
the subcellular localization of LmPRL-1 in promastigotes, amastigotes, and
infected macrophages, we found that the phosphatase was predominantly expressed
and secreted by promastigotes via the exosome route. Finally, we observed that
ectopic expression of LmPRL-1 in L. major led to an increased number of parasites
in macrophages. From these data, we conclude that the L. major phosphatase LmPRL
1 contributes to the intracellular survival of the parasites in macrophages.
PMID- 28507077
TI - Correction.
PMID- 28507075
TI - Metalworking fluids: a new cause of occupational non-asthmatic eosinophilic
bronchitis.
PMID- 28507073
TI - Antibodies against In Vivo-Expressed Antigens Are Sufficient To Protect against
Lethal Aerosol Infection with Burkholderia mallei and Burkholderia pseudomallei.
AB - Burkholderia mallei, a facultative intracellular bacterium and tier 1 biothreat,
causes the fatal zoonotic disease glanders. The organism possesses multiple genes
encoding autotransporter proteins, which represent important virulence factors
and targets for developing countermeasures in pathogenic Gram-negative bacteria.
In the present study, we investigated one of these autotransporters, BatA, and
demonstrate that it displays lipolytic activity, aids in intracellular survival,
is expressed in vivo, elicits production of antibodies during infection, and
contributes to pathogenicity in a mouse aerosol challenge model. A mutation in
the batA gene of wild-type strain ATCC 23344 was found to be particularly
attenuating, as BALB/c mice infected with the equivalent of 80 median lethal
doses cleared the organism. This finding prompted us to test the hypothesis that
vaccination with the batA mutant strain elicits protective immunity against
subsequent infection with wild-type bacteria. We discovered that not only does
vaccination provide high levels of protection against lethal aerosol challenge
with B. mallei ATCC 23344, it also protects against infection with multiple
isolates of the closely related organism and causative agent of melioidosis,
Burkholderia pseudomallei Passive-transfer experiments also revealed that the
protective immunity afforded by vaccination with the batA mutant strain is
predominantly mediated by IgG antibodies binding to antigens expressed
exclusively in vivo Collectively, our data demonstrate that BatA is a target for
developing medical countermeasures and that vaccination with a mutant lacking
expression of the protein provides a platform to gain insights regarding
mechanisms of protective immunity against B. mallei and B. pseudomallei,
including antigen discovery.
PMID- 28507079
TI - Distance constraints on activation of TRPV4 channels by AKAP150-bound PKCalpha in
arterial myocytes.
AB - TRPV4 (transient receptor potential vanilloid 4) channels are Ca2+-permeable
channels that play a key role in regulating vascular tone. In arterial myocytes,
opening of TRPV4 channels creates local increases in Ca2+ influx, detectable
optically as "TRPV4 sparklets." TRPV4 sparklet activity can be enhanced by the
action of the vasoconstrictor angiotensin II (AngII). This modulation depends on
the activation of subcellular signaling domains that comprise protein kinase C
alpha (PKCalpha) bound to the anchoring protein AKAP150. Here, we used super
resolution nanoscopy, patch-clamp electrophysiology, Ca2+ imaging, and
mathematical modeling approaches to test the hypothesis that AKAP150-dependent
modulation of TRPV4 channels is critically dependent on the distance between
these two proteins in the sarcolemma of arterial myocytes. Our data show that the
distance between AKAP150 and TRPV4 channel clusters varies with sex and arterial
bed. Consistent with our hypothesis, we further find that basal and AngII-induced
TRPV4 channel activity decays exponentially as the distance between TRPV4 and
AKAP150 increases. Our data suggest a maximum radius of action of ~200 nm for
local modulation of TRPV4 channels by AKAP150-associated PKCalpha.
PMID- 28507081
TI - Reversion of anergy signatures in clonal CD21low B cells of mixed
cryoglobulinemia after clearance of HCV viremia.
AB - Hepatitis C virus (HCV) causes mixed cryoglobulinemia (MC) by driving clonal
expansion of IgM+CD27+ B cells. These cells display both the features of anergy
induced by continual engagement of the B-cell receptor (BCR), such as high
expression of phosphorylated extracellular signal-regulated kinase (pERK) and
reduced lifespan, and of virus-specific exhaustion, such as CD21low phenotype and
a defective response to ligation of BCR and Toll-like receptor 9 (TLR9). MC
usually regresses after eradication of HCV with interferon, whose
immunomodulatory activity might contribute to this effect. We investigated the
phenotypic and functional changes in clonal B cells of MC patients with sustained
virologic responses to direct-acting antivirals (DAAs), which lack
immunomodulatory properties. We found that high pERK expression and accelerated
apoptosis revert within 4 weeks after beginning therapy, whereas clonal B cells
unresponsive to TLR9 stimulation persist for at least 24 weeks, although they may
partially rescue normal CD21 expression. Thus, similar to mouse models, features
of anergy in MC B cells rapidly revert after disengagement from HCV, whereas
virus-specific exhaustion imparts a durable inhibitory imprint on cell function.
Treatment of HCV+ MC with DAAs provides a valuable tool for untangling the
molecular mechanisms of anergy and exhaustion in human B cells.
PMID- 28507080
TI - Divergent roles of a peripheral transmembrane segment in AMPA and NMDA receptors.
AB - Ionotropic glutamate receptors (iGluRs), including AMPA receptor (AMPAR) and NMDA
receptor (NMDAR) subtypes, are ligand-gated ion channels that mediate signaling
at the majority of excitatory synapses in the nervous system. The iGluR pore
domain is structurally and evolutionarily related to an inverted two
transmembrane K+ channel. Peripheral to the pore domain in eukaryotic iGluRs is
an additional transmembrane helix, the M4 segment, which interacts with the pore
domain of a neighboring subunit. In AMPARs, the integrity of the alignment of a
specific face of M4 with the adjacent pore domain is essential for receptor
oligomerization. In contrast to AMPARs, NMDARs are obligate heterotetramers
composed of two GluN1 and typically two GluN2 subunits. Here, to address the
function of the M4 segments in NMDARs, we carry out a tryptophan scan of M4 in
GluN1 and GluN2A subunits. Unlike AMPARs, the M4 segments in NMDAR subunits makes
only a limited contribution to their biogenesis. However, the M4 segments in both
NMDAR subunits are critical for receptor activation, with mutations at some
positions, most notably at the extreme extracellular end, completely halting the
gating process. Furthermore, although the AMPAR M4 makes a minimal contribution
to receptor desensitization, the NMDAR M4 segments have robust and subunit
specific effects on desensitization. These findings reveal that the functional
roles of the M4 segments in AMPARs and NMDARs have diverged in the course of
their evolution and that the M4 segments in NMDARs may act as a transduction
pathway for receptor modulation at synapses.
PMID- 28507084
TI - Osteopontin attenuates aging-associated phenotypes of hematopoietic stem cells.
PMID- 28507085
TI - Endothelial basement membrane laminin 511 is essential for shear stress response.
PMID- 28507082
TI - Association between diffuse myocardial fibrosis and diastolic dysfunction in
sickle cell anemia.
AB - Sickle cell anemia (SCA)-related cardiomyopathy is characterized by diastolic
dysfunction and hyperdynamic features. Diastolic dysfunction portends early
mortality in SCA. Diastolic dysfunction is associated with microscopic myocardial
fibrosis in SCA mice, but the cause of diastolic dysfunction in humans with SCA
is unknown. We used cardiac magnetic resonance measurements of extracellular
volume fraction (ECV) to discover and quantify diffuse myocardial fibrosis in 25
individuals with SCA (mean age, 23 +/- 13 years) and determine the association
between diffuse myocardial fibrosis and diastolic dysfunction. ECV was calculated
from pre- and post-gadolinium T1 measurements of blood and myocardium, and
diastolic function was assessed by echocardiography. ECV was markedly increased
in all participants compared with controls (0.44 +/- 0.08 vs 0.26 +/- 0.02, P <
.0001), indicating the presence of diffuse myocardial fibrosis. Seventeen
patients (71%) had diastolic abnormalities, and 7 patients (29%) met the
definition of diastolic dysfunction. Participants with diastolic dysfunction had
higher ECV (0.49 +/- 0.07 vs 0.37 +/- 0.04, P = .01) and N-terminal pro-brain
natriuretic peptide (NT-proBNP; 191 +/- 261 vs 33 +/- 33 pg/mL, P = .04) but
lower hemoglobin (8.4 +/- 0.3 vs 10.9 +/- 1.4 g/dL, P = .004) compared with
participants with normal diastolic function. Participants with the highest ECV
values (>=0.40) were more likely to have diastolic dysfunction (P = .003) and
increased left atrial volume (57 +/- 11 vs 46 +/- 12 mL/m2, P = .04) compared
with those with ECV <0.4. ECV correlated with hemoglobin (r = -0.46, P = .03) and
NT-proBNP (r = 0.62, P = .001). In conclusion, diffuse myocardial fibrosis,
determined by ECV, is a common and previously underappreciated feature of SCA
that is associated with diastolic dysfunction, anemia, and high NT-proBNP.
Diffuse myocardial fibrosis is a novel mechanism that appears to underlie
diastolic dysfunction in SCA.
PMID- 28507083
TI - Frequency and epitope specificity of anti-factor VIII C1 domain antibodies in
acquired and congenital hemophilia A.
AB - Several studies showed that neutralizing anti-factor VIII (anti-fVIII) antibodies
(inhibitors) in patients with acquired hemophilia A (AHA) and congenital
hemophilia A (HA) are primarily directed to the A2 and C2 domains. In this study,
the frequency and epitope specificity of anti-C1 antibodies were analyzed in
acquired and congenital hemophilia inhibitor patients (n = 178). The domain
specificity of antibodies was studied by homolog-scanning mutagenesis (HSM) with
single human domain human/porcine fVIII proteins and antibody binding to human
A2, C1, and C2 domains presented as human serum albumin (HSA) fusion proteins.
The analysis with HSA-fVIII domain proteins confirmed the results of the HSM
approach but resulted in higher detection levels. The higher detection levels
with HSA-fVIII domain proteins are a result of antibody cross-reactivity with
human and porcine fVIII leading to false-negative HSM results. Overall, A2-, C1-,
and C2-specific antibodies were detected in 23%, 78%, and 68% of patients with
AHA (n = 115) and in 52%, 57%, and 81% of HA inhibitor patients (n = 63).
Competitive binding of the human monoclonal antibody (mAb) LE2E9 revealed
overlapping epitopes with murine C1-specific group A mAbs including 2A9.
Mutational analyses identified distinct crucial binding residues for LE2E9
(E2066) and 2A9 (F2068) that are also recognized by anti-C1 antibodies present in
patients with hemophilia. A strong contribution of LE2E9- and 2A9-like antibodies
was particularly observed in patients with AHA. Overall, our study demonstrates
that the C1 domain, in addition to the A2 and C2 domains, contributes
significantly to the humoral anti-fVIII immune response in acquired and
congenital hemophilia inhibitor patients.
PMID- 28507086
TI - The role and impact of cost-sharing mechanisms for prescription drug coverage.
PMID- 28507088
TI - Impact of income-based deductibles on drug use and health care utilization among
older adults.
AB - BACKGROUND: Income-based deductibles are present in several provincial public
drug plans in Canada and have been the subject of extensive debate. We studied
the impact of such deductibles in British Columbia's Fair PharmaCare plan on drug
and health care utilization among older adults. METHODS: We used a quasi
experimental regression discontinuity design to compare the impact of deductibles
in BC's PharmaCare plan between older community-dwelling adults registered for
the plan who were born in 1928 through 1939 (no deductible) and those born in
1940 through 1951 (deductible equivalent to 2% of household income). We used 1.2
million person-years of data between 2003 and 2015 to study public drug plan
expenditures, overall drug use, and physician and hospital resource utilization
in these 2 groups. RESULTS: The income-based deductible led to a 28.6% decrease
in person-years in which public drug plan benefits were received (95% confidence
interval [CI] -29.7% to -27.5%) and to a reduction in the per capita extent of
annual benefits by $205.59 (95% CI -$247.81 to -$163.37). Despite this difference
in public subsidy, we found no difference in the number of drugs received or in
total drug spending once privately paid amounts were accounted for (p = 0.4 and
0.8, respectively). Further, we found only small or nonexistent changes in health
care resource utilization at the 1939 threshold. INTERPRETATION: A modest income
based deductible had a considerable impact on the extent of public subsidy for
prescription drugs. However, it had only a trivial impact on overall access to
medicines and use of other health services. Unlike copayments, modest income
based deductibles may safely reduce public spending on drugs for some population
groups.
PMID- 28507089
TI - Atypical pneumonia due to human bocavirus in an immunocompromised patient.
PMID- 28507090
TI - Ocular surface squamous neoplasia in a patient with AIDS.
PMID- 28507087
TI - Influence of environmental temperature on risk of gestational diabetes.
AB - BACKGROUND: Cold-induced thermogenesis is known to improve insulin sensitivity,
which may become increasingly relevant in the face of global warming. The aim of
this study was to examine the relation between outdoor air temperature and the
risk of gestational diabetes mellitus. METHODS: We identified all births in the
Greater Toronto Area from 2002 to 2014 using administrative health databases.
Generalized estimating equations were used to examine the relation between the
mean 30-day outdoor air temperature before the time of gestational diabetes
mellitus screening and the likelihood of diagnosis of gestational diabetes
mellitus based on a validated algorithm using hospital records and physician
service claims. RESULTS: Over the 12-year period, there were 555 911 births among
396 828 women. Prevalence of gestational diabetes mellitus was 4.6% among women
exposed to extremely cold mean outdoor air temperatures (<= -10 degrees C) in the
30-day period before screening and increased to 7.7% among those exposed to hot
mean 30-day temperatures (>= 24 degrees C). Each 10 degrees C increase in mean 30
day temperature was associated with a 1.06 (95% confidence interval [CI] 1.04
1.07) times higher odds of gestational diabetes mellitus, after adjusting for
maternal age, parity, neighbourhood income quintile, world region and year. A
similar effect was seen for each 10 degrees C rise in outdoor air temperature
difference between 2 consecutive pregnancies for the same woman (adjusted odds
ratio 1.06, 95% CI 1.03-1.08). INTERPRETATION: In our setting, there was a direct
relation between outdoor air temperature and the likelihood of gestational
diabetes mellitus. Future climate patterns may substantially affect global
variations in the prevalence of diabetes, which also has important implications
for the prevention and treatment of gestational diabetes mellitus.
PMID- 28507091
TI - Liam Durcan: neurological narrative.
PMID- 28507092
TI - List of essential medicines for Canada.
PMID- 28507093
TI - A priority-setting framework is needed to understand the value of investing in a
universal drug plan.
PMID- 28507094
TI - CIHR announces winners of health research awards.
PMID- 28507095
TI - Reducing inappropriate prescribing easier said than done.
PMID- 28507096
TI - Back to the Future in Alberta.
PMID- 28507098
TI - Cargo engagement protects protease adaptors from degradation in a substrate
specific manner.
AB - Protein degradation in bacteria is a highly controlled process involving
proteolytic adaptors that regulate protein degradation during cell cycle
progression or during stress responses. Many adaptors work as scaffolds that
selectively bind cargo and tether substrates to their cognate proteases to
promote substrate destruction, whereas others primarily activate the target
protease. Because adaptors must bind their cognate protease, all adaptors run the
risk of being recognized by the protease as substrates themselves, a process that
could limit their effectiveness. Here we use purified proteins in a reconstituted
system and in vivo studies to show that adaptors of the ClpXP protease are
readily degraded but that cargo binding inhibits this degradation. We found that
this principle extends across several adaptor systems, including the hierarchical
adaptors that drive the Caulobacter bacterial cell cycle and the quality control
adaptor SspB. We also found that the ability of a cargo to protect its adaptor is
adaptor substrate-specific, as adaptors with artificial degradation tags were not
protected even though cargo binding is unaffected. Our work points to an
optimization of inherent adaptor degradation and cargo binding that ensures that
robust adaptor activity is maintained when high amounts of substrate must be
delivered and that adaptors can be eliminated when their tasks have been
completed.
PMID- 28507097
TI - Gene duplication and neo-functionalization in the evolutionary and functional
divergence of the metazoan copper transporters Ctr1 and Ctr2.
AB - Copper is an essential element for proper organismal development and is involved
in a range of processes, including oxidative phosphorylation, neuropeptide
biogenesis, and connective tissue maturation. The copper transporter (Ctr) family
of integral membrane proteins is ubiquitously found in eukaryotes and mediates
the high-affinity transport of Cu+ across both the plasma membrane and
endomembranes. Although mammalian Ctr1 functions as a Cu+ transporter for Cu
acquisition and is essential for embryonic development, a homologous protein,
Ctr2, has been proposed to function as a low-affinity Cu transporter, a lysosomal
Cu exporter, or a regulator of Ctr1 activity, but its functional and evolutionary
relationship to Ctr1 is unclear. Here we report a biochemical, genetic, and
phylogenetic comparison of metazoan Ctr1 and Ctr2, suggesting that Ctr2 arose
over 550 million years ago as a result of a gene duplication event followed by
loss of Cu+ transport activity. Using a random mutagenesis and growth selection
approach, we identified amino acid substitutions in human and mouse Ctr2 proteins
that support copper-dependent growth in yeast and enhance copper accumulation in
Ctr1-/- mouse embryonic fibroblasts. These mutations revert Ctr2 to a more
ancestral Ctr1-like state while maintaining endogenous functions, such as
stimulating Ctr1 cleavage. We suggest key structural aspects of metazoan Ctr1 and
Ctr2 that discriminate between their biological roles, providing mechanistic
insights into the evolutionary, biochemical, and functional relationships between
these two related proteins.
PMID- 28507099
TI - Carbon dioxide-dependent regulation of NF-kappaB family members RelB and p100
gives molecular insight into CO2-dependent immune regulation.
AB - CO2 is a physiological gas normally produced in the body during aerobic
respiration. Hypercapnia (elevated blood pCO2 >~50 mm Hg) is a feature of several
lung pathologies, e.g. chronic obstructive pulmonary disease. Hypercapnia is
associated with increased susceptibility to bacterial infections and suppression
of inflammatory signaling. The NF-kappaB pathway has been implicated in these
effects; however, the molecular mechanisms underpinning cellular sensitivity of
the NF-kappaB pathway to CO2 are not fully elucidated. Here, we identify several
novel CO2-dependent changes in the NF-kappaB pathway. NF-kappaB family members
p100 and RelB translocate to the nucleus in response to CO2 A cohort of RelB
protein-protein interactions (e.g. with Raf-1 and IkappaBalpha) are altered by
CO2 exposure, although others are maintained (e.g. with p100). RelB is processed
by CO2 in a manner dependent on a key C-terminal domain located in its
transactivation domain. Loss of the RelB transactivation domain alters NF-kappaB
dependent transcriptional activity, and loss of p100 alters sensitivity of RelB
to CO2 Thus, we provide molecular insight into the CO2 sensitivity of the NF
kappaB pathway and implicate altered RelB/p100-dependent signaling in the CO2
dependent regulation of inflammatory signaling.
PMID- 28507100
TI - The microRNA machinery regulates fasting-induced changes in gene expression and
longevity in Caenorhabditis elegans.
AB - Intermittent fasting (IF) is a dietary restriction regimen that extends the
lifespans of Caenorhabditis elegans and mammals by inducing changes in gene
expression. However, how IF induces these changes and promotes longevity remains
unclear. One proposed mechanism involves gene regulation by microRNAs (miRNAs),
small non-coding RNAs (~22 nucleotides) that repress gene expression and whose
expression can be altered by fasting. To test this proposition, we examined the
role of the miRNA machinery in fasting-induced transcriptional changes and
longevity in C. elegans We revealed that fasting up-regulated the expression of
the miRNA-induced silencing complex (miRISC) components, including Argonaute and
GW182, and the miRNA-processing enzyme DRSH-1 (the ortholog of the Drosophila
Drosha enzyme). Our lifespan measurements demonstrated that IF-induced longevity
was suppressed by knock-out or knockdown of miRISC components and was completely
inhibited by drsh-1 ablation. Remarkably, drsh-1 ablation inhibited the fasting
induced changes in the expression of the target genes of DAF-16, the insulin/IGF
1 signaling effector in C. elegans Fasting-induced transcriptome alterations were
substantially and modestly suppressed in the drsh-1 null mutant and the null
mutant of ain-1, a gene encoding GW182, respectively. Moreover, miRNA array
analyses revealed that the expression levels of numerous miRNAs changed after 2
days of fasting. These results indicate that components of the miRNA machinery,
especially the miRNA-processing enzyme DRSH-1, play an important role in
mediating IF-induced longevity via the regulation of fasting-induced changes in
gene expression.
PMID- 28507101
TI - Human myosin VIIa is a very slow processive motor protein on various cellular
actin structures.
AB - Human myosin VIIa (MYO7A) is an actin-linked motor protein associated with human
Usher syndrome (USH) type 1B, which causes human congenital hearing and visual
loss. Although it has been thought that the role of human myosin VIIa is critical
for USH1 protein tethering with actin and transportation along actin bundles in
inner-ear hair cells, myosin VIIa's motor function remains unclear. Here, we
studied the motor function of the tail-truncated human myosin VIIa dimer
(HM7ADeltaTail/LZ) at the single-molecule level. We found that the
HM7ADeltaTail/LZ moves processively on single actin filaments with a step size of
35 nm. Dwell-time distribution analysis indicated an average waiting time of 3.4
s, yielding ~0.3 s-1 for the mechanical turnover rate; hence, the velocity of
HM7ADeltaTail/LZ was extremely slow, at 11 nm.s-1 We also examined
HM7ADeltaTail/LZ movement on various actin structures in demembranated cells.
HM7ADeltaTail/LZ showed unidirectional movement on actin structures at cell
edges, such as lamellipodia and filopodia. However, HM7ADeltaTail/LZ frequently
missed steps on actin tracks and exhibited bidirectional movement at stress
fibers, which was not observed with tail-truncated myosin Va. These results
suggest that the movement of the human myosin VIIa motor protein is more
efficient on lamellipodial and filopodial actin tracks than on stress fibers,
which are composed of actin filaments with different polarity, and that the actin
structures influence the characteristics of cargo transportation by human myosin
VIIa. In conclusion, myosin VIIa movement appears to be suitable for
translocating USH1 proteins on stereocilia actin bundles in inner-ear hair cells.
PMID- 28507104
TI - Genetic Characterization of Broad-Host-Range IncQ Plasmids Harboring blaVEB-18 in
Vibrio Species.
PMID- 28507103
TI - Nicotinic Acid Phosphoribosyltransferase Regulates Cancer Cell Metabolism,
Susceptibility to NAMPT Inhibitors, and DNA Repair.
AB - In the last decade, substantial efforts have been made to identify NAD+
biosynthesis inhibitors, specifically against nicotinamide
phosphoribosyltransferase (NAMPT), as preclinical studies indicate their
potential efficacy as cancer drugs. However, the clinical activity of NAMPT
inhibitors has proven limited, suggesting that alternative NAD+ production routes
exploited by tumors confer resistance. Here, we show the gene encoding nicotinic
acid phosphoribosyltransferase (NAPRT), a second NAD+-producing enzyme, is
amplified and overexpressed in a subset of common types of cancer, including
ovarian cancer, where NAPRT expression correlates with a BRCAness gene expression
signature. Both NAPRT and NAMPT increased intracellular NAD+ levels. NAPRT
silencing reduced energy status, protein synthesis, and cell size in ovarian and
pancreatic cancer cells. NAPRT silencing sensitized cells to NAMPT inhibitors
both in vitro and in vivo; similar results were obtained with the NAPRT inhibitor
2-hydroxynicotinic acid. Reducing NAPRT levels in a BRCA2-deficient cancer cell
line exacerbated DNA damage in response to chemotherapeutics. In conclusion,
NAPRT-dependent NAD+ biosynthesis contributes to cell metabolism and to the DNA
repair process in a subset of tumors. This knowledge could be used to increase
the efficacy of NAMPT inhibitors and chemotherapy. Cancer Res; 77(14); 3857-69.
(c)2017 AACR.
PMID- 28507102
TI - The FOXO3/PGC-1beta signaling axis is essential for cancer stem cell properties
of pancreatic ductal adenocarcinoma.
AB - In 95% of patients with pancreatic ductal adenocarcinoma, recurrence is observed
following chemotherapy. Findings from several studies have indicated that cancer
stem cells (CSCs) are resistant to anticancer agents and may be involved in
cancer recurrence and metastasis. The CD44 protein is a major CSC marker, and
CD44 also plays an indispensable role in the CSC properties in several cancers,
including pancreatic cancer; however, no clinical approach exists to inhibit CD44
activity. Here, we have performed knock-in/knockdown experiments, and we
demonstrate that the forkhead box O3 (FOXO3)/liver kinase B1 (LKB1)/AMP-activated
protein kinase/peroxisome proliferator-activated receptor-gamma co-activator
1beta (PGC-1beta)/pyruvate dehydrogenase-A1 pathway is essential for CD44
expression and CSC properties. We observed that patients exhibiting high pyruvate
dehydrogenase-A1 expression have a poor prognosis. Systemic PGC-1beta knock-out
mice are fertile and viable and do not exhibit an overt phenotype under normal
conditions. This suggests that cGMP induction and PGC-1beta inhibition represent
potential strategies for treating patients with pancreatic ductal adenocarcinoma.
PMID- 28507105
TI - Reduced Vancomycin Susceptibility of Methicillin-Susceptible Staphylococcus
aureus Has No Significant Impact on Mortality but Results in an Increase in
Complicated Infection.
AB - Methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections
(BSIs) often lead to severe complications despite the availability of effective
antibiotics. It remains unclear whether elevated vancomycin MICs are associated
with worse outcomes. We conducted a 2-year retrospective cohort study (n = 252)
of patients with MSSA BSIs at a tertiary care hospital. We defined reduced
vancomycin susceptibility (RVS) as a Microscan MIC of 2 mg/liter. All strains
were genotyped (spa) and assessed for agr functionality. Multivariable logistic
regression models were used to examine the impact of RVS phenotype and strain
genotype on 30-day all-cause mortality and complicated bacteremia (metastatic
spread, endovascular infection, or duration >=3 days). One-third of patients
(84/252) were infected with RVS isolates. RVS Infections were more frequently
associated with metastatic or embolic sites of infection (36% versus 17%, P <
0.001), and endovascular infection (26% versus 12%, P = 0.004). These infections
occurred more often in patients with fewer underlying comorbidities (Charlson
comorbidity index of >=3 [73% versus 88%, P = 0.002]). Genotyping identified 127
spa-types and 14 Spa-clonal complexes (Spa-CCs). Spa-CC002 and Spa-CC008 were
more likely to exhibit the RVS phenotype versus other Spa-CCs (OR = 2.2, P <
0.01). The RVS phenotype was not significantly associated with 30-day mortality;
however, it was associated with complicated bacteremia (adjusted odds ratio of
2.35 [range, 1.26 to 4.37]; P = 0.007) in adjusted analyses. The association of
RVS strains with complicated infection and fewer underlying comorbidities
suggests the phenotype as a potential marker of strain virulence in MSSA BSIs.
The RVS phenotype itself was not a significant predictor of mortality in this
patient cohort. Further studies are necessary to explore this host-pathogen
relationship.
PMID- 28507106
TI - Efficacy and Pharmacokinetics of the Combination of OP0595 and Cefepime in a
Mouse Model of Pneumonia Caused by Extended-Spectrum-Beta-Lactamase-Producing
Klebsiella pneumoniae.
AB - OP0595 (RG6080) is a novel diazabicyclooctane that inhibits class A and C serine
beta-lactamases. Although the combination of OP0595 and cefepime (FEP) showed
good in vitro activity against extended-spectrum-beta-lactamase (ESBL)-producing
pathogens, the effect of the combination therapy against severe infections, such
as pneumonia or bacteremia, remains unknown in vivo In this study, we
investigated the efficacy and pharmacokinetics of the combination therapy of
OP0595 and FEP in a mouse model of pneumonia caused by Klebsiella pneumoniae
harboring SHV- and CTX-M-9-type ESBLs. The infected BALB/c mice were
intraperitoneally administered saline (control), 100 mg/kg of body weight of FEP,
20 mg/kg of OP0595, or both FEP and OP0595, twice a day. The MIC of FEP against
the bacteria was 8 mg/liter and markedly improved to 0.06 mg/liter with the
addition of 0.5 mg/ml of OP0595. In the survival study, the combination of FEP
and OP0595 significantly improved the survival rate compared with that reported
with either OP0595 or FEP alone (P < 0.001). The number of bacteria in the lungs
and blood significantly decreased in the combination therapy group compared to
that reported for the monotherapy groups (P < 0.001). In addition, the in vivo
effect depended on the dose of FEP. However, pharmacokinetic analysis revealed
that the percentage of time above MIC remained constant when increasing the dose
of FEP in combination with 20 mg/kg of OP0595. The results of our study
demonstrated the in vivo effectiveness of the combination of OP0595 and FEP.
PMID- 28507107
TI - In Vitro Cross-Resistance Profiles of Rilpivirine, Dapivirine, and MIV-150,
Nonnucleoside Reverse Transcriptase Inhibitor Microbicides in Clinical
Development for the Prevention of HIV-1 Infection.
AB - Rilpivirine (RPV), dapivirine (DPV), and MIV-150 are in development as
microbicides. It is not known whether they will block infection of circulating
nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant human
immunodeficiency virus type 1 (HIV-1) variants. Here, we demonstrate that the
activity of DPV and MIV-150 is compromised by many resistant viruses containing
single or double substitutions. High DPV genital tract concentrations from DPV
ring use may block replication of resistant viruses. However, MIV-150 genital
tract concentrations may be insufficient to inhibit many resistant viruses,
including those harboring K103N or Y181C.
PMID- 28507108
TI - Safety, Pharmacokinetics, and Antiviral Activity of a Novel HIV Antiviral,
ABX464, in Treatment-Naive HIV-Infected Subjects in a Phase 2 Randomized,
Controlled Study.
AB - We investigated the safety and antiviral effects of an anti-HIV compound (ABX464)
with a unique mechanism of viral replication inhibition. This was a randomized,
double-blind, placebo-controlled, dose-ranging study in treatment-naive HIV
infected patients. Participants were assigned to eight groups; each group
included eight subjects receiving either the study compound, ABX464 (n = 6), or
the corresponding placebo (n = 2), according to a randomization code. The first
dose administered was 25 mg, given once or 3 times a day over a 2- to 3-week
period. Ascending doses of up to 150 mg were delivered after review of the safety
data. The primary objective of the study was to assess the safety and
tolerability of ABX464 after repeated oral administrations in subjects infected
by HIV. Sixty-six subjects were enrolled and were randomized. Sixty-three
subjects completed the study according to the study protocol. Twenty-one adverse
events (AEs) were reported by 7 subjects out of 16 (44%) who received placebo,
and 158 AEs were reported by 39 subjects out of 50 (78%) who received the study
drug. In the ABX464 treatment group, all of these adverse events were mild to
moderate. No subjects discontinued treatment due to drug-related AEs.
Administration of ABX464 at up to 150 mg once a day was safe and well tolerated
in HIV-infected subjects. An efficacy signal with respect to a reduction of the
viral load by ABX464 was detected, mainly in subjects treated at the highest
dose. Further studies will be required to demonstrate antiviral effects in HIV
infected subjects in combination with other antiretroviral therapies. (This study
is registered on the ClinicalTrials.gov website under registration no.
NCT02452242.).
PMID- 28507110
TI - Controlled Release of Plectasin NZ2114 from a Hybrid Silicone-Hydrogel Material
for Inhibition of Staphylococcus aureus Biofilm.
AB - Staphylococcus aureus is a major human pathogen in catheter-related infections.
Modifying catheter material with interpenetrating polymer networks is a novel
material technology that allows for impregnation with drugs and subsequent
controlled release. Here, we evaluated the potential for combining this system
with plectasin derivate NZ2114 in an attempt to design an S. aureus biofilm
resistant catheter. The material demonstrated promising antibiofilm properties,
including properties against methicillin-resistant S. aureus, thus suggesting a
novel application of this antimicrobial peptide.
PMID- 28507109
TI - ERG11 Gene Mutations and MDR1 Upregulation Confer Pan-Azole Resistance in Candida
tropicalis Causing Disseminated Candidiasis in an Acute Lymphoblastic Leukemia
Patient on Posaconazole Prophylaxis.
AB - In this study, we present a rare case of fatal breakthrough Candida tropicalis
infection in a patient with acute lymphoblastic leukemia (ALL) while on
posaconazole prophylaxis. Then, we explore the mechanisms underlying azole
resistance by focusing on enhanced efflux pumps and changes in the azole target
enzyme Erg11p, which was encoded by the ERG11 gene. Our study demonstrates that
Y132C substitution of Erg11p combined with MDR1 overexpression may be the pan
azole resistance mechanisms in Candida tropicalis.
PMID- 28507111
TI - Real-Life Assessment of the Safety and Effectiveness of the New Tablet and
Intravenous Formulations of Posaconazole in the Prophylaxis of Invasive Fungal
Infections via Analysis of 343 Courses.
AB - Posaconazole is the preferred mold-active azole for prophylaxis against invasive
fungal infections (IFIs) in patients with hematological malignancy. Delayed
release tablet and intravenous formulations of posaconazole have recently become
available, but clinical data are limited. We sought to examine the real-world
pharmacokinetics and prophylactic effectiveness of the new formulations of
posaconazole given as prophylaxis for patients with hematological malignancy. A
retrospective cohort of all consecutive adult inpatients with hematological
malignancy who received >=3 days of tablet or intravenous posaconazole therapy
for primary IFI prophylaxis at the M. D. Anderson Cancer Center between 1
December 2013 and 31 December 2015 was established. Clinical information was
collected and correlated with low posaconazole serum levels (<700 ng/ml). Rates
of IFIs and safety events were assessed. A total of 1,321 courses of posaconazole
were administered at the M. D. Anderson Cancer Center during the study period, of
which 343 courses were assessed for prophylactic safety and effectiveness.
Seventy-nine patients (23%) had posaconazole serum level measurements available
for interpretation. Acute myeloid leukemia was the primary malignancy (62%), with
20% of all patients having previously received a stem cell transplant. The median
posaconazole level was 1,380 ng/ml (interquartile range, 864 to 1,860 ng/ml). Low
posaconazole levels (<700 ng/ml) were observed for 14 patients (18%). Proven or
probable breakthrough IFIs occurred in 8 patients (2%); posaconazole therapeutic
drug monitoring (TDM) was performed for 6 of those patients, all with levels
above 700 ng/ml. Overall, 19% of patients experienced grade 3 or 4 liver injury,
manifesting primarily as hyperbilirubinemia and being correlated with serum
levels of >1,830 ng/ml. Although hepatotoxicity in a small percentage of patients
is of concern, posaconazole tablets appeared to be generally safe and effective.
As all breakthrough IFIs for which TDM was performed occurred in patients with
levels of >700 ng/ml, and a posaconazole level of >1,830 ng/ml was correlated
with grade 3 or 4 liver toxicity, further studies are needed to assess the role
of TDM.
PMID- 28507112
TI - MCR-1 and OXA-48 In Vivo Acquisition in KPC-Producing Escherichia coli after
Colistin Treatment.
AB - The spread of mcr-1-encoding plasmids into carbapenem-resistant
Enterobacteriaceae raises concerns about the emergence of untreatable bacteria.
We report the acquisition of mcr-1 in a carbapenem-resistant Escherichia coli
strain after a 3-week course of colistin in a patient repatriated to France from
Portugal. Whole-genome sequencing revealed that the Klebsiella pneumoniae
carbapenemase-producing E. coli strain acquired two plasmids, an IncL OXA-48
encoding plasmid and an IncX4 mcr-1-encoding plasmid. This is the first report of
mcr-1 in carbapenemase-encoding bacteria in France.
PMID- 28507114
TI - Antiviral Activity of Nordihydroguaiaretic Acid and Its Derivative Tetra-O-Methyl
Nordihydroguaiaretic Acid against West Nile Virus and Zika Virus.
AB - Flaviviruses are positive-strand RNA viruses distributed all over the world that
infect millions of people every year and for which no specific antiviral agents
have been approved. These viruses include the mosquito-borne West Nile virus
(WNV), which is responsible for outbreaks of meningitis and encephalitis.
Considering that nordihydroguaiaretic acid (NDGA) has been previously shown to
inhibit the multiplication of the related dengue virus and hepatitis C virus, we
have evaluated the effect of NDGA, and its methylated derivative tetra-O-methyl
nordihydroguaiaretic acid (M4N), on the infection of WNV. Both compounds
inhibited the infection of WNV, likely by impairing viral replication. Since
flavivirus multiplication is highly dependent on host cell lipid metabolism, the
antiviral effect of NDGA has been previously related to its ability to disturb
the lipid metabolism, probably by interfering with the sterol regulatory element
binding proteins (SREBP) pathway. Remarkably, we observed that other structurally
unrelated inhibitors of the SREBP pathway, such as PF-429242 and fatostatin, also
reduced WNV multiplication, supporting that the SREBP pathway may constitute a
druggable target suitable for antiviral intervention against flavivirus
infection. Moreover, treatment with NDGA, M4N, PF-429242, and fatostatin also
inhibited the multiplication of the mosquito-borne flavivirus Zika virus (ZIKV),
which has been recently associated with birth defects (microcephaly) and
neurological disorders. Our results point to SREBP inhibitors, such as NDGA and
M4N, as potential candidates for further antiviral development against medically
relevant flaviviruses.
PMID- 28507115
TI - Sensitivity of White and Opaque Candida albicans Cells to Antifungal Drugs.
AB - White and opaque cells of Candida albicans have the same genome but differ in
gene expression patterns, metabolic profiles, and host niche preferences. We
tested whether these differences, which include the differential expression of
drug transporters, resulted in different sensitivities to 27 antifungal agents.
The analysis was performed in two different strain backgrounds; although there
was strain-to-strain variation, only terbinafine hydrochloride and caspofungin
showed consistent, 2-fold differences between white and opaque cells across both
strains.
PMID- 28507113
TI - Efficacy of a Binuclear Cyclopalladated Compound Therapy for Cutaneous
Leishmaniasis in the Murine Model of Infection with Leishmania amazonensis and
Its Inhibitory Effect on Topoisomerase 1B.
AB - Leishmaniasis is a disease found throughout the (sub)tropical parts of the world
caused by protozoan parasites of the Leishmania genus. Despite the numerous
problems associated with existing treatments, pharmaceutical companies continue
to neglect the development of better ones. The high toxicity of current drugs
combined with emerging resistance makes the discovery of new therapeutic
alternatives urgent. We report here the evaluation of a binuclear cyclopalladated
complex containing Pd(II) and N,N'-dimethylbenzylamine (Hdmba) against Leishmania
amazonensis The compound [Pd(dmba)(MU-N3)]2 (CP2) inhibits promastigote growth
(50% inhibitory concentration [IC50] = 13.2 +/- 0.7 MUM) and decreases the
proliferation of intracellular amastigotes in in vitro incubated macrophages
(IC50 = 10.2 +/- 2.2 MUM) without a cytotoxic effect when tested against
peritoneal macrophages (50% cytotoxic concentration = 506.0 +/- 10.7 MUM). In
addition, CP2 was also active against T. cruzi intracellular amastigotes (IC50 =
2.3 +/- 0.5 MUM, selective index = 225), an indication of its potential for use
in Chagas disease therapy. In vivo assays using L. amazonensis-infected BALB/c
showed an 80% reduction in parasite load compared to infected and nontreated
animals. Also, compared to amphotericin B treatment, CP2 did not show any side
effects, which was corroborated by the analysis of plasma levels of different
hepatic and renal biomarkers. Furthermore, CP2 was able to inhibit Leishmania
donovani topoisomerase 1B (Ldtopo1B), a potentially important target in this
parasite. (This study has been registered at ClinicalTrials.gov under identifier
NCT02169141.).
PMID- 28507116
TI - Toxic Electrophiles Induce Expression of the Multidrug Efflux Pump MexEF-OprN in
Pseudomonas aeruginosa through a Novel Transcriptional Regulator, CmrA.
AB - The multidrug efflux system MexEF-OprN is produced at low levels in wild-type
strains of Pseudomonas aeruginosa However, in so-called nfxC mutants, mutational
alteration of the gene mexS results in constitutive overexpression of the pump,
along with increased resistance of the bacterium to chloramphenicol,
fluoroquinolones, and trimethoprim. In this study, analysis of in vitro-selected
chloramphenicol-resistant clones of strain PA14 led to the identification of a
new class of MexEF-OprN-overproducing mutants (called nfxC2) exhibiting
alterations in an as-yet-uncharacterized gene, PA14_38040 (homolog of PA2047 in
strain PAO1). This gene is predicted to encode an AraC-like transcriptional
regulator and was called cmrA (for chloramphenicol resistance activator). In
nfxC2 mutants, the mutated CmrA increases its proper gene expression and
upregulates the operon mexEF-oprN through MexS and MexT, resulting in a multidrug
resistance phenotype without significant loss in bacterial virulence.
Transcriptomic experiments demonstrated that CmrA positively regulates a small
set of 11 genes, including PA14_38020 (homolog of PA2048), which is required for
the MexS/T-dependent activation of mexEF-oprN PA2048 codes for a protein sharing
conserved domains with the quinol monooxygenase YgiN from Escherichia coli
Interestingly, exposure of strain PA14 to toxic electrophilic molecules (glyoxal,
methylglyoxal, and cinnamaldehyde) strongly activates the CmrA pathway and
upregulates MexEF-OprN and, thus, increases the resistance of P. aeruginosa to
the pump substrates. A picture emerges in which MexEF-OprN is central in the
response of the pathogen to stresses affecting intracellular redox homeostasis.
PMID- 28507117
TI - Pharmacokinetics of Levofloxacin in Multidrug- and Extensively Drug-Resistant
Tuberculosis Patients.
AB - Pharmacodynamics are especially important in the treatment of multidrug- and
extensively drug-resistant tuberculosis (M/XDR-TB). The free area under the
concentration time curve in relation to MIC (fAUC/MIC) is the most relevant
pharmacokinetic (PK)-pharmacodynamic (PD) parameter for predicting the efficacy
of levofloxacin (LFX). The objective of our study was to assess LFX PK
variability in M/XDR-TB patients and its potential consequence for fAUC/MIC
ratios. Patients with pulmonary M/XDR-TB received LFX as part of the treatment
regimen at a dose of 15 mg/kg administered once daily. Blood samples obtained at
steady state before and 1, 2, 3, 4, 7, and 12 h after drug administration were
measured by validated liquid chromatography-tandem mass spectrometry. The MIC
values of LFX were determined by the agar dilution method on Middlebrook 7H10 and
the MGIT960 system. Twenty patients with a mean age of 31 years (interquartile
range [IQR] = 27 to 35 years) were enrolled in this study. The median AUC0-24 was
98.8 mg/h/liter (IQR = 84.8 to 159.6 mg/h/liter). The MIC median value for LFX
was 0.5 mg/liter with a range of 0.25 to 2.0 mg/liter, and the median fAUC0
24/MIC ratio was 109.5 (IQR = 48.5 to 399.4). In 4 of the 20 patients, the value
was below the target value of >=100. When MICs of 0.25, 0.5, 1.0, and 2.0
mg/liter were applicable, 19, 18, 3, and no patients, respectively, had an
fAUC/MIC ratio that exceeded 100. We observed a large variability in AUC. An
fAUC0-24/MIC of >=100 was only observed when the MIC values for LFX were 0.25 to
0.5 mg/liter. Dosages exceeding 15 mg/kg should be considered for target
attainment if exposures are assumed to be safe. (This study has been registered
at ClinicalTrials.gov under registration no. NCT02169141.).
PMID- 28507118
TI - Colistin Resistance in Carbapenem-Resistant Klebsiella pneumoniae Mediated by
Chromosomal Integration of Plasmid DNA.
AB - Here we describe the spread of colistin resistance in clinical isolates of
carbapenem-resistant Klebsiella pneumoniae in Medellin, Colombia. Among 32
isolates collected between 2012 and 2014, 24 showed genetic alterations in mgrB
Nineteen isolates belonged to sequence type 512 (ST512) (or its single locus
variant [SLV]) and harbored an 8.1-kb hsdMSR insertion corresponding to ISKpn25,
indicating a clonal expansion of the resistant strain. The insertion region
showed 100% identity to several plasmids, suggesting that the colistin resistance
is mediated by chromosomal integration of plasmid DNA.
PMID- 28507120
TI - Highly active catalyst derived from a 3D foam of Fe(PO3)2/Ni2P for extremely
efficient water oxidation.
AB - Commercial hydrogen production by electrocatalytic water splitting will benefit
from the realization of more efficient and less expensive catalysts compared with
noble metal catalysts, especially for the oxygen evolution reaction, which
requires a current density of 500 mA/cm2 at an overpotential below 300 mV with
long-term stability. Here we report a robust oxygen-evolving electrocatalyst
consisting of ferrous metaphosphate on self-supported conductive nickel foam that
is commercially available in large scale. We find that this catalyst, which may
be associated with the in situ generated nickel-iron oxide/hydroxide and iron
oxyhydroxide catalysts at the surface, yields current densities of 10 mA/cm2 at
an overpotential of 177 mV, 500 mA/cm2 at only 265 mV, and 1,705 mA/cm2 at 300
mV, with high durability in alkaline electrolyte of 1 M KOH even after 10,000
cycles, representing activity enhancement by a factor of 49 in boosting water
oxidation at 300 mV relative to the state-of-the-art IrO2 catalyst.
PMID- 28507119
TI - Regulation of the sperm calcium channel CatSper by endogenous steroids and plant
triterpenoids.
AB - The calcium channel of sperm (CatSper) is essential for sperm hyperactivated
motility and fertility. The steroid hormone progesterone activates CatSper of
human sperm via binding to the serine hydrolase ABHD2. However, steroid
specificity of ABHD2 has not been evaluated. Here, we explored whether steroid
hormones to which human spermatozoa are exposed in the male and female genital
tract influence CatSper activation via modulation of ABHD2. The results show that
testosterone, estrogen, and hydrocortisone did not alter basal CatSper currents,
whereas the neurosteroid pregnenolone sulfate exerted similar effects as
progesterone, likely binding to the same site. However, physiological
concentrations of testosterone and hydrocortisone inhibited CatSper activation by
progesterone. Additionally, testosterone antagonized the effect of pregnenolone
sulfate. We have also explored whether steroid-like molecules, such as the plant
triterpenoids pristimerin and lupeol, affect sperm fertility. Interestingly, both
compounds competed with progesterone and pregnenolone sulfate and significantly
reduced CatSper activation by either steroid. Furthermore, pristimerin and lupeol
considerably diminished hyperactivation of capacitated spermatozoa. These results
indicate that (i) pregnenolone sulfate together with progesterone are the main
steroids that activate CatSper and (ii) pristimerin and lupeol can act as
contraceptive compounds by averting sperm hyperactivation, thus preventing
fertilization.
PMID- 28507121
TI - Essential information: Uncertainty and optimal control of Ebola outbreaks.
AB - Early resolution of uncertainty during an epidemic outbreak can lead to rapid and
efficient decision making, provided that the uncertainty affects prioritization
of actions. The wide range in caseload projections for the 2014 Ebola outbreak
caused great concern and debate about the utility of models. By coding and
running 37 published Ebola models with five candidate interventions, we found
that, despite this large variation in caseload projection, the ranking of
management options was relatively consistent. Reducing funeral transmission and
reducing community transmission were generally ranked as the two best options.
Value of information (VoI) analyses show that caseloads could be reduced by 11%
by resolving all model-specific uncertainties, with information about model
structure accounting for 82% of this reduction and uncertainty about caseload
only accounting for 12%. Our study shows that the uncertainty that is of most
interest epidemiologically may not be the same as the uncertainty that is most
relevant for management. If the goal is to improve management outcomes, then the
focus of study should be to identify and resolve those uncertainties that most
hinder the choice of an optimal intervention. Our study further shows that
simplifying multiple alternative models into a smaller number of relevant groups
(here, with shared structure) could streamline the decision-making process and
may allow for a better integration of epidemiological modeling and decision
making for policy.
PMID- 28507123
TI - Large-moment antiferromagnetic order in overdoped high-Tc superconductor
154SmFeAsO1-x D x.
AB - In iron-based superconductors, high critical temperature (Tc) superconductivity
over 50 K has only been accomplished in electron-doped hREFeAsO (hRE is heavy
rare earth (RE) element). Although hREFeAsO has the highest bulk Tc (58 K),
progress in understanding its physical properties has been relatively slow due to
difficulties in achieving high-concentration electron doping and carrying out
neutron experiments. Here, we present a systematic neutron powder diffraction
study of 154SmFeAsO1-x D x , and the discovery of a long-range antiferromagnetic
ordering with x >= 0.56 (AFM2) accompanying a structural transition from
tetragonal to orthorhombic. Surprisingly, the Fe magnetic moment in AFM2 reaches
a magnitude of 2.73 MUB/Fe, which is the largest in all nondoped iron pnictides
and chalcogenides. Theoretical calculations suggest that the AFM2 phase
originates in kinetic frustration of the Fe-3dxy orbital, in which the nearest
neighbor hopping parameter becomes zero. The unique phase diagram, i.e., highest
Tc superconducting phase adjacent to the strongly correlated phase in electron
overdoped regime, yields important clues to the unconventional origins of
superconductivity.
PMID- 28507125
TI - Effective control of complex turbulent dynamical systems through statistical
functionals.
AB - Turbulent dynamical systems characterized by both a high-dimensional phase space
and a large number of instabilities are ubiquitous among complex systems in
science and engineering, including climate, material, and neural science. Control
of these complex systems is a grand challenge, for example, in mitigating the
effects of climate change or safe design of technology with fully developed shear
turbulence. Control of flows in the transition to turbulence, where there is a
small dimension of instabilities about a basic mean state, is an important and
successful discipline. In complex turbulent dynamical systems, it is impossible
to track and control the large dimension of instabilities, which strongly
interact and exchange energy, and new control strategies are needed. The goal of
this paper is to propose an effective statistical control strategy for complex
turbulent dynamical systems based on a recent statistical energy principle and
statistical linear response theory. We illustrate the potential practical
efficiency and verify this effective statistical control strategy on the 40D
Lorenz 1996 model in forcing regimes with various types of fully turbulent
dynamics with nearly one-half of the phase space unstable.
PMID- 28507124
TI - Thiophene antibacterials that allosterically stabilize DNA-cleavage complexes
with DNA gyrase.
AB - A paucity of novel acting antibacterials is in development to treat the rising
threat of antimicrobial resistance, particularly in Gram-negative hospital
pathogens, which has led to renewed efforts in antibiotic drug discovery.
Fluoroquinolones are broad-spectrum antibacterials that target DNA gyrase by
stabilizing DNA-cleavage complexes, but their clinical utility has been
compromised by resistance. We have identified a class of antibacterial thiophenes
that target DNA gyrase with a unique mechanism of action and have activity
against a range of bacterial pathogens, including strains resistant to
fluoroquinolones. Although fluoroquinolones stabilize double-stranded DNA breaks,
the antibacterial thiophenes stabilize gyrase-mediated DNA-cleavage complexes in
either one DNA strand or both DNA strands. X-ray crystallography of DNA gyrase
DNA complexes shows the compounds binding to a protein pocket between the winged
helix domain and topoisomerase-primase domain, remote from the DNA. Mutations of
conserved residues around this pocket affect activity of the thiophene
inhibitors, consistent with allosteric inhibition of DNA gyrase. This druggable
pocket provides potentially complementary opportunities for targeting bacterial
topoisomerases for antibiotic development.
PMID- 28507122
TI - Control of metastatic niche formation by targeting APBA3/Mint3 in inflammatory
monocytes.
AB - Cancer metastasis is intricately orchestrated by both cancer and normal cells,
such as endothelial cells and macrophages. Monocytes/macrophages, which are often
co-opted by cancer cells and promote tumor malignancy, acquire more than half of
their energy from glycolysis even during normoxic conditions. This glycolytic
activity is maintained during normoxia by the functions of hypoxia inducible
factor 1 (HIF-1) and its activator APBA3. The mechanism by which APBA3 inhibition
partially suppresses macrophage function and affects cancer metastasis is of
interest in view of avoidance of the adverse effects of complete suppression of
macrophage function during therapy. Here, we report that APBA3-deficient mice
show reduced metastasis, with no apparent effect on primary tumor growth. APBA3
deficiency in inflammatory monocytes, which strongly express the chemokine
receptor CCR2 and are recruited toward chemokine CCL2 from metastatic sites,
hampers glycolysis-dependent chemotaxis of cells toward metastatic sites and
inhibits VEGFA expression, similar to the effects observed with HIF-1 deficiency.
Host APBA3 induces VEGFA-mediated E-selectin expression in the endothelial cells
of target organs, thereby promoting extravasation of cancer cells and
micrometastasis formation. Administration of E-selectin-neutralizing antibody
also abolished host APBA3-mediated metastatic formation. Thus, targeting APBA3 is
useful for controlling metastatic niche formation by inflammatory monocytes.
PMID- 28507126
TI - Direct observation of structure and dynamics during phase separation of an
elastomeric protein.
AB - Despite its growing importance in biology and in biomaterials development, liquid
liquid phase separation of proteins remains poorly understood. In particular, the
molecular mechanisms underlying simple coacervation of proteins, such as the
extracellular matrix protein elastin, have not been reported. Coacervation of the
elastin monomer, tropoelastin, in response to heat and salt is a critical step in
the assembly of elastic fibers in vivo, preceding chemical cross-linking. Elastin
like polypeptides (ELPs) derived from the tropoelastin sequence have been shown
to undergo a similar phase separation, allowing formation of biomaterials that
closely mimic the material properties of native elastin. We have used NMR
spectroscopy to obtain site-specific structure and dynamics of a self-assembling
elastin-like polypeptide along its entire self-assembly pathway, from monomer
through coacervation and into a cross-linked elastic material. Our data reveal
that elastin-like hydrophobic domains are composed of transient beta-turns in a
highly dynamic and disordered chain, and that this disorder is retained both
after phase separation and in elastic materials. Cross-linking domains are also
highly disordered in monomeric and coacervated ELP3 and form stable helices only
after chemical cross-linking. Detailed structural analysis combined with dynamic
measurements from NMR relaxation and diffusion data provides direct evidence for
an entropy-driven mechanism of simple coacervation of a protein in which
transient and nonspecific intermolecular hydrophobic contacts are formed by
disordered chains, whereas bulk water and salt are excluded.
PMID- 28507128
TI - Exceptional and rapid accumulation of anthropogenic debris on one of the world's
most remote and pristine islands.
AB - In just over half a century plastic products have revolutionized human society
and have infiltrated terrestrial and marine environments in every corner of the
globe. The hazard plastic debris poses to biodiversity is well established, but
mitigation and planning are often hampered by a lack of quantitative data on
accumulation patterns. Here we document the amount of debris and rate of
accumulation on Henderson Island, a remote, uninhabited island in the South
Pacific. The density of debris was the highest reported anywhere in the world, up
to 671.6 items/m2 (mean +/- SD: 239.4 +/- 347.3 items/m2) on the surface of the
beaches. Approximately 68% of debris (up to 4,496.9 pieces/m2) on the beach was
buried <10 cm in the sediment. An estimated 37.7 million debris items weighing a
total of 17.6 tons are currently present on Henderson, with up to 26.8 new
items/m accumulating daily. Rarely visited by humans, Henderson Island and other
remote islands may be sinks for some of the world's increasing volume of waste.
PMID- 28507127
TI - Development of visual category selectivity in ventral visual cortex does not
require visual experience.
AB - To what extent does functional brain organization rely on sensory input? Here, we
show that for the penultimate visual-processing region, ventral-temporal cortex
(VTC), visual experience is not the origin of its fundamental organizational
property, category selectivity. In the fMRI study reported here, we presented 14
congenitally blind participants with face-, body-, scene-, and object-related
natural sounds and presented 20 healthy controls with both auditory and visual
stimuli from these categories. Using macroanatomical alignment, response mapping,
and surface-based multivoxel pattern analysis, we demonstrated that VTC in blind
individuals shows robust discriminatory responses elicited by the four categories
and that these patterns of activity in blind subjects could successfully predict
the visual categories in sighted controls. These findings were confirmed in a
subset of blind participants born without eyes and thus deprived from all light
perception since conception. The sounds also could be decoded in primary visual
and primary auditory cortex, but these regions did not sustain generalization
across modalities. Surprisingly, although not as strong as visual responses,
selectivity for auditory stimulation in visual cortex was stronger in blind
individuals than in controls. The opposite was observed in primary auditory
cortex. Overall, we demonstrated a striking similarity in the cortical response
layout of VTC in blind individuals and sighted controls, demonstrating that the
overall category-selective map in extrastriate cortex develops independently from
visual experience.
PMID- 28507129
TI - Nonpeptide orexin type-2 receptor agonist ameliorates narcolepsy-cataplexy
symptoms in mouse models.
AB - Narcolepsy-cataplexy is a debilitating disorder of sleep/wakefulness caused by a
loss of orexin-producing neurons in the lateroposterior hypothalamus. Genetic or
pharmacologic orexin replacement ameliorates symptoms in mouse models of
narcolepsy-cataplexy. We have recently discovered a potent, nonpeptide OX2R
selective agonist, YNT-185. This study validates the pharmacological activity of
this compound in OX2R-transfected cells and in OX2R-expressing neurons in brain
slice preparations. Intraperitoneal, and intracerebroventricular, administration
of YNT-185 suppressed cataplexy-like episodes in orexin knockout and orexin
neuron-ablated mice, but not in orexin receptor-deficient mice. Peripherally
administered YNT-185 also promotes wakefulness without affecting body temperature
in wild-type mice. Further, there was no immediate rebound sleep after YNT-185
administration in active phase in wild-type and orexin-deficient mice. No
desensitization was observed after repeated administration of YNT-185 with
respect to the suppression of cataplexy-like episodes. These results provide a
proof-of-concept for a mechanistic therapy of narcolepsy-cataplexy by OX2R
agonists.
PMID- 28507130
TI - Spatially restricted dental regeneration drives pufferfish beak development.
AB - Vertebrate dentitions are extraordinarily diverse in both morphology and
regenerative capacity. The teleost order Tetraodontiformes exhibits an
exceptional array of novel dental morphologies, epitomized by constrained beak
like dentitions in several families, i.e., porcupinefishes, three-toothed
pufferfishes, ocean sunfishes, and pufferfishes. Modification of tooth
replacement within these groups leads to the progressive accumulation of tooth
generations, underlying the structure of their beaks. We focus on the dentition
of the pufferfish (Tetraodontidae) because of its distinct dental morphology.
This complex dentition develops as a result of (i) a reduction in the number of
tooth positions from seven to one per quadrant during the transition from first
to second tooth generations and (ii) a dramatic shift in tooth morphogenesis
following the development of the first-generation teeth, leading to the
elongation of dental units along the jaw. Gene expression and 1,1'-Dioctadecyl
3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) lineage tracing reveal a
putative dental epithelial progenitor niche, suggesting a highly conserved
mechanism for tooth regeneration despite the development of a unique dentition.
MicroCT analysis reveals restricted labial openings in the beak, through which
the dental epithelium (lamina) invades the cavity of the highly mineralized beak.
Reduction in the number of replacement tooth positions coincides with the
development of only four labial openings in the pufferfish beak, restricting
connection of the oral epithelium to the dental cavity. Our data suggest the
spatial restriction of dental regeneration, coupled with the unique extension of
the replacement dental units throughout the jaw, are primary contributors to the
evolution and development of this unique beak-like dentition.
PMID- 28507132
TI - Identification of Cav2-PKCbeta and Cav2-NOS1 complexes as entities for ultrafast
electrochemical coupling.
AB - Voltage-activated calcium (Cav) channels couple intracellular signaling pathways
to membrane potential by providing Ca2+ ions as second messengers at sufficiently
high concentrations to modulate effector proteins located in the intimate
vicinity of those channels. Here we show that protein kinase Cbeta (PKCbeta) and
brain nitric oxide synthase (NOS1), both identified by proteomic analysis as
constituents of the protein nano-environment of Cav2 channels in the brain,
directly coassemble with Cav2.2 channels upon heterologous coexpression. Within
Cav2.2-PKCbeta and Cav2.2-NOS1 complexes voltage-triggered Ca2+ influx through
the Cav channels reliably initiates enzymatic activity within milliseconds. Using
BKCa channels as target sensors for nitric oxide and protein phosphorylation
together with high concentrations of Ca2+ buffers showed that the complex
mediated Ca2+ signaling occurs in local signaling domains at the plasma membrane.
Our results establish Cav2-enzyme complexes as molecular entities for fast
electrochemical coupling that reliably convert brief membrane depolarization into
precisely timed intracellular signaling events in the mammalian brain.
PMID- 28507131
TI - Involvement of a gut-retina axis in protection against dietary glycemia-induced
age-related macular degeneration.
AB - Age-related macular degeneration (AMD) is the major cause of blindness in
developed nations. AMD is characterized by retinal pigmented epithelial (RPE)
cell dysfunction and loss of photoreceptor cells. Epidemiologic studies indicate
important contributions of dietary patterns to the risk for AMD, but the
mechanisms relating diet to disease remain unclear. Here we investigate the
effect on AMD of isocaloric diets that differ only in the type of dietary
carbohydrate in a wild-type aged-mouse model. The consumption of a high-glycemia
(HG) diet resulted in many AMD features (AMDf), including RPE hypopigmentation
and atrophy, lipofuscin accumulation, and photoreceptor degeneration, whereas
consumption of the lower-glycemia (LG) diet did not. Critically, switching from
the HG to the LG diet late in life arrested or reversed AMDf. LG diets limited
the accumulation of advanced glycation end products, long-chain polyunsaturated
lipids, and their peroxidation end-products and increased C3-carnitine in retina,
plasma, or urine. Untargeted metabolomics revealed microbial cometabolites,
particularly serotonin, as protective against AMDf. Gut microbiota were
responsive to diet, and we identified microbiota in the Clostridiales order as
being associated with AMDf and the HG diet, whereas protection from AMDf was
associated with the Bacteroidales order and the LG diet. Network analysis
revealed a nexus of metabolites and microbiota that appear to act within a gut
retina axis to protect against diet- and age-induced AMDf. The findings indicate
a functional interaction between dietary carbohydrates, the metabolome, including
microbial cometabolites, and AMDf. Our studies suggest a simple dietary
intervention that may be useful in patients to arrest AMD.
PMID- 28507133
TI - Cholinergic shaping of neural correlations.
AB - A primary function of the brain is to form representations of the sensory world.
Its capacity to do so depends on the relationship between signal correlations,
associated with neuronal receptive fields, and noise correlations, associated
with neuronal response variability. It was recently shown that the behavioral
relevance of sensory stimuli can modify the relationship between signal and noise
correlations, presumably increasing the encoding capacity of the brain. In this
work, we use data from the visual cortex of the awake mouse watching naturalistic
stimuli and show that a similar modification is observed under heightened
cholinergic modulation. Increasing cholinergic levels in the cortex through
optogenetic stimulation of basal forebrain cholinergic neurons decreases the
dependency that is commonly observed between signal and noise correlations.
Simulations of correlated neural networks with realistic firing statistics
indicate that this change in the correlation structure increases the encoding
capacity of the network.
PMID- 28507134
TI - Dopaminergic modulation of basal ganglia output through coupled excitation
inhibition.
AB - Learning and maintenance of skilled movements require exploration of motor space
and selection of appropriate actions. Vocal learning and social context-dependent
plasticity in songbirds depend on a basal ganglia circuit, which actively
generates vocal variability. Dopamine in the basal ganglia reduces trial-to-trial
neural variability when the bird engages in courtship song. Here, we present
evidence for a unique, tonically active, excitatory interneuron in the songbird
basal ganglia that makes strong synaptic connections onto output pallidal
neurons, often linked in time with inhibitory events. Dopamine receptor activity
modulates the coupling of these excitatory and inhibitory events in vitro, which
results in a dynamic change in the synchrony of a modeled population of basal
ganglia output neurons receiving excitatory and inhibitory inputs. The excitatory
interneuron thus serves as one biophysical mechanism for the introduction or
modulation of neural variability in this circuit.
PMID- 28507135
TI - Parallel memory traces are built after an experience containing aversive and
appetitive components in the crab Neohelice.
AB - The neurobiology of learning and memory has been mainly studied by focusing on
pure aversive or appetitive experiences. Here, we challenged this approach
considering that real-life stimuli come normally associated with competing
aversive and appetitive consequences and that interaction between conflicting
information must be intrinsic part of the memory processes. We used Neohelice
crabs, taking advantage of two well-described appetitive and aversive learning
paradigms and combining them in a single training session to evaluate how this
affects memory. We found that crabs build separate appetitive and aversive
memories that compete during retrieval but not during acquisition. Which memory
prevails depends on the balance between the strength of the unconditioned stimuli
and on the motivational state of the animals. The results indicate that after a
mix experience with appetitive and aversive consequences, parallel memories are
established in a way that appetitive and aversive information is stored to be
retrieved in an opportunistic manner.
PMID- 28507136
TI - OCD candidate gene SLC1A1/EAAT3 impacts basal ganglia-mediated activity and
stereotypic behavior.
AB - Obsessive-compulsive disorder (OCD) is a chronic, disabling condition with
inadequate treatment options that leave most patients with substantial residual
symptoms. Structural, neurochemical, and behavioral findings point to a
significant role for basal ganglia circuits and for the glutamate system in OCD.
Genetic linkage and association studies in OCD point to SLC1A1, which encodes the
neuronal glutamate/aspartate/cysteine transporter excitatory amino acid
transporter 3 (EAAT3)/excitatory amino acid transporter 1 (EAAC1). However, no
previous studies have investigated EAAT3 in basal ganglia circuits or in relation
to OCD-related behavior. Here, we report a model of Slc1a1 loss based on an
excisable STOP cassette that yields successful ablation of EAAT3 expression and
function. Using amphetamine as a probe, we found that EAAT3 loss prevents
expected increases in (i) locomotor activity, (ii) stereotypy, and (iii)
immediate early gene induction in the dorsal striatum following amphetamine
administration. Further, Slc1a1-STOP mice showed diminished grooming in an SKF
38393 challenge experiment, a pharmacologic model of OCD-like grooming behavior.
This reduced grooming is accompanied by reduced dopamine D1 receptor binding in
the dorsal striatum of Slc1a1-STOP mice. Slc1a1-STOP mice also exhibit reduced
extracellular dopamine concentrations in the dorsal striatum both at baseline and
following amphetamine challenge. Viral-mediated restoration of Slc1a1/EAAT3
expression in the midbrain but not in the striatum results in partial rescue of
amphetamine-induced locomotion and stereotypy in Slc1a1-STOP mice, consistent
with an impact of EAAT3 loss on presynaptic dopaminergic function. Collectively,
these findings indicate that the most consistently associated OCD candidate gene
impacts basal ganglia-dependent repetitive behaviors.
PMID- 28507137
TI - Arabidopsis glycosylphosphatidylinositol-anchored protein LLG1 associates with
and modulates FLS2 to regulate innate immunity.
AB - Plants detect and respond to pathogen invasion with membrane-localized pattern
recognition receptors (PRRs), which recognize pathogen-associated molecular
patterns (PAMPs) and activate downstream immune responses. Here we report that
Arabidopsis thaliana LORELEI-LIKE GPI-ANCHORED PROTEIN 1 (LLG1), a coreceptor of
the receptor-like kinase FERONIA, regulates PRR signaling. In a forward genetic
screen for suppressors of enhanced disease resistance 1 (edr1), we identified the
point mutation llg1-3, which suppresses edr1 disease resistance but does not
affect plant growth and development. The llg1 mutants show enhanced
susceptibility to various virulent pathogens, indicating that LLG1 has an
important role in plant immunity. LLG1 constitutively associates with the PAMP
receptor FLAGELLIN SENSING 2 (FLS2) and the elongation factor-Tu receptor, and
forms a complex with BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED RECEPTOR KINASE 1
in a ligand-dependent manner, indicating that LLG1 functions as a key component
of PAMP-recognition immune complexes. Moreover, LLG1 contributes to accumulation
and ligand-induced degradation of FLS2, and is required for downstream innate
immunity responses, including ligand-induced phosphorylation of BOTRYTIS-INDUCED
KINASE 1 and production of reactive oxygen species. Taken together, our findings
reveal that LLG1 associates with PAMP receptors and modulates their function to
regulate disease responses. As LLG1 functions as a coreceptor of FERONIA and
plays central roles in plant growth and development, our findings indicate that
LLG1 participates in separate pathways, and may suggest a potential connection
between development and innate immunity in plants.
PMID- 28507138
TI - Stem cell migration and mechanotransduction on linear stiffness gradient
hydrogels.
AB - The spatial presentation of mechanical information is a key parameter for cell
behavior. We have developed a method of polymerization control in which the
differential diffusion distance of unreacted cross-linker and monomer into a
prepolymerized hydrogel sink results in a tunable stiffness gradient at the cell
matrix interface. This simple, low-cost, robust method was used to produce
polyacrylamide hydrogels with stiffness gradients of 0.5, 1.7, 2.9, 4.5, 6.8, and
8.2 kPa/mm, spanning the in vivo physiological and pathological mechanical
landscape. Importantly, three of these gradients were found to be nondurotactic
for human adipose-derived stem cells (hASCs), allowing the presentation of a
continuous range of stiffnesses in a single well without the confounding effect
of differential cell migration. Using these nondurotactic gradient gels,
stiffness-dependent hASC morphology, migration, and differentiation were studied.
Finally, the mechanosensitive proteins YAP, Lamin A/C, Lamin B, MRTF-A, and MRTF
B were analyzed on these gradients, providing higher-resolution data on stiffness
dependent expression and localization.
PMID- 28507140
TI - Linkage disequilibrium matches forensic genetic records to disjoint genomic
marker sets.
AB - Combining genotypes across datasets is central in facilitating advances in
genetics. Data aggregation efforts often face the challenge of record matching
the identification of dataset entries that represent the same individual. We show
that records can be matched across genotype datasets that have no shared markers
based on linkage disequilibrium between loci appearing in different datasets.
Using two datasets for the same 872 people-one with 642,563 genome-wide SNPs and
the other with 13 short tandem repeats (STRs) used in forensic applications-we
find that 90-98% of forensic STR records can be connected to corresponding SNP
records and vice versa. Accuracy increases to 99-100% when ~30 STRs are used. Our
method expands the potential of data aggregation, but it also suggests privacy
risks intrinsic in maintenance of databases containing even small numbers of
markers-including databases of forensic significance.
PMID- 28507139
TI - Long-read sequencing uncovers the adaptive topography of a carnivorous plant
genome.
AB - Utricularia gibba, the humped bladderwort, is a carnivorous plant that retains a
tiny nuclear genome despite at least two rounds of whole genome duplication (WGD)
since common ancestry with grapevine and other species. We used a third
generation genome assembly with several complete chromosomes to reconstruct the
two most recent lineage-specific ancestral genomes that led to the modern U.
gibba genome structure. Patterns of subgenome dominance in the most recent WGD,
both architectural and transcriptional, are suggestive of allopolyploidization,
which may have generated genomic novelty and led to instantaneous speciation.
Syntenic duplicates retained in polyploid blocks are enriched for transcription
factor functions, whereas gene copies derived from ongoing tandem duplication
events are enriched in metabolic functions potentially important for a
carnivorous plant. Among these are tandem arrays of cysteine protease genes with
trap-specific expression that evolved within a protein family known to be useful
in the digestion of animal prey. Further enriched functions among tandem
duplicates (also with trap-enhanced expression) include peptide transport
(intercellular movement of broken-down prey proteins), ATPase activities (bladder
trap acidification and transmembrane nutrient transport), hydrolase and chitinase
activities (breakdown of prey polysaccharides), and cell-wall dynamic components
possibly associated with active bladder movements. Whereas independently
polyploid Arabidopsis syntenic gene duplicates are similarly enriched for
transcriptional regulatory activities, Arabidopsis tandems are distinct from
those of U. gibba, while still metabolic and likely reflecting unique adaptations
of that species. Taken together, these findings highlight the special importance
of tandem duplications in the adaptive landscapes of a carnivorous plant genome.
PMID- 28507141
TI - Pulses of Ca2+ coordinate actin assembly and exocytosis for stepwise cell
extension.
AB - Many eukaryotic cells grow by extending their cell periphery in pulses. The
molecular mechanisms underlying this process are not yet fully understood. Here
we present a comprehensive model of stepwise cell extension by using the unique
tip growth system of filamentous fungi. Live-cell imaging analysis, including
superresolution microscopy, revealed that the fungus Aspergillus nidulans extends
the hyphal tip in an oscillatory manner. The amount of F-actin and secretory
vesicles (SV) accumulating at the hyphal tip oscillated with a positive temporal
correlation, whereas vesicle amounts were negatively correlated to the growth
rate. The intracellular Ca2+ level also pulsed with a positive temporal
correlation to the amount of F-actin and SV at the hyphal tip. Two Ca2+ channels,
MidA and CchA, were needed for proper tip growth and the oscillations of actin
polymerization, exocytosis, and the growth rate. The data indicate a model in
which transient Ca2+ pluses cause depolymerization of F-actin at the cortex and
promote SV fusion with the plasma membrane, thereby extending the cell tip. Over
time, Ca2+ diffuses away and F-actin and SV accumulate again at the hyphal tip.
Our data provide evidence that temporally controlled actin polymerization and
exocytosis are coordinated by pulsed Ca2+ influx, resulting in stepwise cell
extension.
PMID- 28507143
TI - Controllable load sharing for soft adhesive interfaces on three-dimensional
surfaces.
AB - For adhering to three-dimensional (3D) surfaces or objects, current adhesion
systems are limited by a fundamental trade-off between 3D surface conformability
and high adhesion strength. This limitation arises from the need for a soft,
mechanically compliant interface, which enables conformability to nonflat and
irregularly shaped surfaces but significantly reduces the interfacial fracture
strength. In this work, we overcome this trade-off with an adhesion-based soft
gripping system that exhibits enhanced fracture strength without sacrificing
conformability to nonplanar 3D surfaces. Composed of a gecko-inspired elastomeric
microfibrillar adhesive membrane supported by a pressure-controlled deformable
gripper body, the proposed soft-gripping system controls the bonding strength by
changing its internal pressure and exploiting the mechanics of interfacial equal
load sharing. The soft adhesion system can use up to ~26% of the maximum adhesion
of the fibrillar membrane, which is 14* higher than the adhering membrane without
load sharing. Our proposed load-sharing method suggests a paradigm for soft
adhesion-based gripping and transfer-printing systems that achieves area scaling
similar to that of a natural gecko footpad.
PMID- 28507142
TI - Quantitative assessment of passive electrical properties of the cardiac T-tubular
system by FRAP microscopy.
AB - Well-coordinated activation of all cardiomyocytes must occur on every heartbeat.
At the cell level, a complex network of sarcolemmal invaginations, called the
transverse-axial tubular system (TATS), propagates membrane potential changes to
the cell core, ensuring synchronous and uniform excitation-contraction coupling.
Although myocardial conduction of excitation has been widely described, the
electrical properties of the TATS remain mostly unknown. Here, we exploit the
formal analogy between diffusion and electrical conductivity to link the latter
with the diffusional properties of TATS. Fluorescence recovery after
photobleaching (FRAP) microscopy is used to probe the diffusion properties of
TATS in isolated rat cardiomyocytes: A fluorescent dextran inside TATS lumen is
photobleached, and signal recovery by diffusion of unbleached dextran from the
extracellular space is monitored. We designed a mathematical model to correlate
the time constant of fluorescence recovery with the apparent diffusion
coefficient of the fluorescent molecules. Then, apparent diffusion is linked to
electrical conductivity and used to evaluate the efficiency of the passive spread
of membrane depolarization along TATS. The method is first validated in cells
where most TATS elements are acutely detached by osmotic shock and then applied
to probe TATS electrical conductivity in failing heart cells. We find that acute
and pathological tubular remodeling significantly affect TATS electrical
conductivity. This may explain the occurrence of defects in action potential
propagation at the level of single T-tubules, recently observed in diseased
cardiomyocytes.
PMID- 28507144
TI - Critical roles of DNA demethylation in the activation of ripening-induced genes
and inhibition of ripening-repressed genes in tomato fruit.
AB - DNA methylation is a conserved epigenetic mark important for genome integrity,
development, and environmental responses in plants and mammals. Active DNA
demethylation in plants is initiated by a family of 5-mC DNA glycosylases/lyases
(i.e., DNA demethylases). Recent reports suggested a role of active DNA
demethylation in fruit ripening in tomato. In this study, we generated loss-of
function mutant alleles of a tomato gene, SlDML2, which is a close homolog of the
Arabidopsis DNA demethylase gene ROS1 In the fruits of the tomato mutants,
increased DNA methylation was found in thousands of genes. These genes included
not only hundreds of ripening-induced genes but also many ripening-repressed
genes. Our results show that SlDML2 is critical for tomato fruit ripening and
suggest that active DNA demethylation is required for both the activation of
ripening-induced genes and the inhibition of ripening-repressed genes.
PMID- 28507146
TI - Further evidence for localized, short-term anthropogenic forest alterations
across pre-Columbian Amazonia.
PMID- 28507145
TI - In vivo photolabeling of tumor-infiltrating cells reveals highly regulated egress
of T-cell subsets from tumors.
AB - Immune therapy is rapidly gaining prominence in the clinic as a major weapon
against cancer. Whereas much attention has been focused on the infiltration of
tumors by immune cells, the subsequent fate of these infiltrates remains largely
unexplored. We therefore established a photoconversion-based model that allowed
us to label tumor-infiltrating immune cells and follow their migration. Using
this system, we identified a population of tumor-experienced cells that emigrate
from primary tumors to draining lymph nodes via afferent lymphatic vessels.
Although the majority of tumor-infiltrating cells were myeloid, T cells made up
the largest population of tumor-egressing leukocytes. Strikingly, the subset
composition of tumor-egressing T cells was greatly skewed compared with those
that had infiltrated the tumor and those resident in the draining lymph node.
Some T-cell subsets such as CD8+ T cells emigrated more readily; others including
CD4-CD8- T cells were preferentially retained, suggesting that specific
mechanisms guide immune cell egress from tumors. Furthermore, tumor-egressing T
cells were more activated and displayed enhanced effector function in comparison
with their lymph node counterparts. Finally, we demonstrated that tumor
infiltrating T cells migrate to distant secondary tumors and draining lymph
nodes, highlighting a mechanism whereby tumor-experienced effector T cells may
mediate antitumor immunity at metastatic sites. Thus, our results provide
insights into migration and function of tumor-infiltrating immune cells and the
role of these cells in tumor immunity outside of primary tumor deposits.
PMID- 28507147
TI - Plate tectonic regulation of global marine animal diversity.
AB - Valentine and Moores [Valentine JW, Moores EM (1970) Nature 228:657-659]
hypothesized that plate tectonics regulates global biodiversity by changing the
geographic arrangement of continental crust, but the data required to fully test
the hypothesis were not available. Here, we use a global database of marine
animal fossil occurrences and a paleogeographic reconstruction model to test the
hypothesis that temporal patterns of continental fragmentation have impacted
global Phanerozoic biodiversity. We find a positive correlation between global
marine invertebrate genus richness and an independently derived quantitative
index describing the fragmentation of continental crust during supercontinental
coalescence-breakup cycles. The observed positive correlation between global
biodiversity and continental fragmentation is not readily attributable to
commonly cited vagaries of the fossil record, including changing quantities of
marine rock or time-variable sampling effort. Because many different
environmental and biotic factors may covary with changes in the geographic
arrangement of continental crust, it is difficult to identify a specific causal
mechanism. However, cross-correlation indicates that the state of continental
fragmentation at a given time is positively correlated with the state of global
biodiversity for tens of millions of years afterward. There is also evidence to
suggest that continental fragmentation promotes increasing marine richness, but
that coalescence alone has only a small negative or stabilizing effect. Together,
these results suggest that continental fragmentation, particularly during the
Mesozoic breakup of the supercontinent Pangaea, has exerted a first-order control
on the long-term trajectory of Phanerozoic marine animal diversity.
PMID- 28507148
TI - Correction for Hobbie et al., Contrasting nitrogen and phosphorus budgets in
urban watersheds and implications for managing urban water pollution.
PMID- 28507150
TI - Trust and the poverty trap.
PMID- 28507151
TI - Assembly and function of bHLH-PAS complexes.
PMID- 28507149
TI - Identification of XAF1-MT2A mutual antagonism as a molecular switch in cell-fate
decisions under stressful conditions.
AB - XIAP-associated factor 1 (XAF1) is a tumor suppressor that is commonly
inactivated in multiple human neoplasms. However, the molecular mechanism
underlying its proapoptotic function remains largely undefined. Here, we report
that XAF1 induction by heavy metals triggers an apoptotic switch of stress
response by destabilizing metallothionein 2A (MT2A). XAF1 directly interacts with
MT2A and facilitates its lysosomal degradation, resulting in the elevation of the
free intercellular zinc level and subsequent activation of p53 and inactivation
of XIAP. Intriguingly, XAF1 is activated as a unique transcription target of
metal-regulatory transcription factor-1 (MTF-1) in signaling apoptosis, and its
protein is destabilized via the lysosomal pathway by MTF-1-induced MT2A under
cytostatic stress conditions, indicating the presence of mutual antagonism
between XAF1 and MT2A. The antagonistic interplay between XAF1 and MT2A acts as a
key molecular switch in MTF-1-mediated cell-fate decisions and also plays an
important role in cell response to various apoptotic and survival factors. Wild
type (WT) XAF1 but not MT2A binding-deficient mutant XAF1 increases the free
intracellular zinc level and accelerates WT folding of p53 and degradation of
XIAP. Consistently, XAF1 evokes a more drastic apoptotic effect in p53+/+ versus
isogenic p53-/- cells. Clinically, expression levels of XAF1 and MT2A are
inversely correlated in primary colon tumors and multiple cancer cell lines. XAF1
depleted xenograft tumors display an increased growth rate and a decreased
apoptotic response to cytotoxic heavy metals with strong MT2A expression.
Collectively, this study uncovers an important role for XAF1-MT2A antagonism as a
linchpin to govern cell fate under various stressful conditions including heavy
metal exposure.
PMID- 28507153
TI - Overexplaining or underexplaining methane's role in climate change.
PMID- 28507154
TI - Information socialtaxis and efficient collective behavior emerging in groups of
information-seeking agents.
AB - Individual behavior, in biology, economics, and computer science, is often
described in terms of balancing exploration and exploitation. Foraging has been a
canonical setting for studying reward seeking and information gathering, from
bacteria to humans, mostly focusing on individual behavior. Inspired by the
gradient-climbing nature of chemotaxis, the infotaxis algorithm showed that
locally maximizing the expected information gain leads to efficient and
ethological individual foraging. In nature, as well as in theoretical settings,
conspecifics can be a valuable source of information about the environment.
Whereas the nature and role of interactions between animals have been studied
extensively, the design principles of information processing in such groups are
mostly unknown. We present an algorithm for group foraging, which we term
"socialtaxis," that unifies infotaxis and social interactions, where each
individual in the group simultaneously maximizes its own sensory information and
a social information term. Surprisingly, we show that when individuals aim to
increase their information diversity, efficient collective behavior emerges in
groups of opportunistic agents, which is comparable to the optimal group
behavior. Importantly, we show the high efficiency of biologically plausible
socialtaxis settings, where agents share little or no information and rely on
simple computations to infer information from the behavior of their conspecifics.
Moreover, socialtaxis does not require parameter tuning and is highly robust to
sensory and behavioral noise. We use socialtaxis to predict distinct optimal
couplings in groups of selfish vs. altruistic agents, reflecting how it can be
naturally extended to study social dynamics and collective computation in general
settings.
PMID- 28507155
TI - Reply to Piperno et al.: It is too soon to argue for localized, short-term human
impacts in interfluvial Amazonia.
PMID- 28507152
TI - Embryonic transcription factor SOX9 drives breast cancer endocrine resistance.
AB - The estrogen receptor (ER) drives the growth of most luminal breast cancers and
is the primary target of endocrine therapy. Although ER blockade with drugs such
as tamoxifen is very effective, a major clinical limitation is the development of
endocrine resistance especially in the setting of metastatic disease. Preclinical
and clinical observations suggest that even following the development of
endocrine resistance, ER signaling continues to exert a pivotal role in tumor
progression in the majority of cases. Through the analysis of the ER cistrome in
tamoxifen-resistant breast cancer cells, we have uncovered a role for an RUNX2-ER
complex that stimulates the transcription of a set of genes, including most
notably the stem cell factor SOX9, that promote proliferation and a metastatic
phenotype. We show that up-regulation of SOX9 is sufficient to cause relative
endocrine resistance. The gain of SOX9 as an ER-regulated gene associated with
tamoxifen resistance was validated in a unique set of clinical samples supporting
the need for the development of improved ER antagonists.
PMID- 28507156
TI - RNA primer-primase complexes serve as the signal for polymerase recycling and
Okazaki fragment initiation in T4 phage DNA replication.
AB - The opposite strand polarity of duplex DNA necessitates that the leading strand
is replicated continuously whereas the lagging strand is replicated in discrete
segments known as Okazaki fragments. The lagging-strand polymerase sometimes
recycles to begin the synthesis of a new Okazaki fragment before finishing the
previous fragment, creating a gap between the Okazaki fragments. The mechanism
and signal that initiate this behavior-that is, the signaling mechanism-have not
been definitively identified. We examined the role of RNA primer-primase
complexes left on the lagging ssDNA from primer synthesis in initiating early
lagging-strand polymerase recycling. We show for the T4 bacteriophage DNA
replication system that primer-primase complexes have a residence time similar to
the timescale of Okazaki fragment synthesis and the ability to block a holoenzyme
synthesizing DNA and stimulate the dissociation of the holoenzyme to trigger
polymerase recycling. The collision with primer-primase complexes triggering the
early termination of Okazaki fragment synthesis has distinct advantages over
those previously proposed because this signal requires no transmission to the
lagging-strand polymerase through protein or DNA interactions, the mechanism for
rapid dissociation of the holoenzyme is always collision, and no unique
characteristics need to be assigned to either identical polymerase in the
replisome. We have modeled repeated cycles of Okazaki fragment initiation using a
collision with a completed Okazaki fragment or primer-primase complexes as the
recycling mechanism. The results reproduce experimental data, providing insights
into events related to Okazaki fragment initiation and the overall functioning of
DNA replisomes.
PMID- 28507158
TI - Impact of International Monetary Fund programs on child health.
AB - Parental education is located at the center of global efforts to improve child
health. In a developing-country context, the International Monetary Fund (IMF)
plays a crucial role in determining how governments allocate scarce resources to
education and public health interventions. Under reforms mandated by IMF
structural adjustment programs, it may become harder for parents to reap the
benefits of their education due to wage contraction, welfare retrenchment, and
generalized social insecurity. This study assesses how the protective effect of
education changes under IMF programs, and thus how parents' ability to guard
their children's health is affected by structural adjustment. We combine cross
sectional stratified data (countries, 67; children, 1,941,734) from the
Demographic and Health Surveys and the Multiple Indicator Cluster Surveys. The
sample represents ~2.8 billion (about 50%) of the world's population in year
2000. Based on multilevel models, our findings reveal that programs reduce the
protective effect of parental education on child health, especially in rural
areas. For instance, in the absence of IMF programs, living in an household with
educated parents reduces the odds of child malnourishment by 38% [odds ratio
(OR), 0.62; 95% CI, 0.66-0.58]; in the presence of programs, this drops to 21%
(OR, 0.79; 95% CI, 0.86-0.74). In other words, the presence of IMF conditionality
decreases the protective effect of parents' education on child malnourishment by
no less than 17%. We observe similar adverse effects in sanitation, shelter, and
health care access (including immunization), but a beneficial effect in
countering water deprivation.
PMID- 28507159
TI - Investigation of hindwing folding in ladybird beetles by artificial elytron
transplantation and microcomputed tomography.
AB - Ladybird beetles are high-mobility insects and explore broad areas by switching
between walking and flying. Their excellent wing transformation systems enabling
this lifestyle are expected to provide large potential for engineering
applications. However, the mechanism behind the folding of their hindwings
remains unclear. The reason is that ladybird beetles close the elytra ahead of
wing folding, preventing the observation of detailed processes occurring under
the elytra. In the present study, artificial transparent elytra were transplanted
on living ladybird beetles, thereby enabling us to observe the detailed wing
folding processes. The result revealed that in addition to the abdominal
movements mentioned in previous studies, the edge and ventral surface of the
elytra, as well as characteristic shaped veins, play important roles in wing
folding. The structures of the wing frames enabling this folding process and
detailed 3D shape of the hindwing were investigated using microcomputed
tomography. The results showed that the tape spring-like elastic frame plays an
important role in the wing transformation mechanism. Compared with other beetles,
hindwings in ladybird beetles are characterized by two seemingly incompatible
properties: (i) the wing rigidity with relatively thick veins and (ii) the
compactness in stored shapes with complex crease patterns. The detailed wing
folding process revealed in this study is expected to facilitate understanding of
the naturally optimized system in this excellent deployable structure.
PMID- 28507157
TI - Translation and folding of single proteins in real time.
AB - Protein biosynthesis is inherently coupled to cotranslational protein folding.
Folding of the nascent chain already occurs during synthesis and is mediated by
spatial constraints imposed by the ribosomal exit tunnel as well as self
interactions. The polypeptide's vectorial emergence from the ribosomal tunnel
establishes the possible folding pathways leading to its native tertiary
structure. How cotranslational protein folding and the rate of synthesis are
linked to a protein's amino acid sequence is still not well defined. Here, we
follow synthesis by individual ribosomes using dual-trap optical tweezers and
observe simultaneous folding of the nascent polypeptide chain in real time. We
show that observed stalling during translation correlates with slowed peptide
bond formation at successive proline sequence positions and electrostatic
interactions between positively charged amino acids and the ribosomal tunnel. We
also determine possible cotranslational folding sites initiated by hydrophobic
collapse for an unstructured and two globular proteins while directly measuring
initial cotranslational folding forces. Our study elucidates the intricate
relationship among a protein's amino acid sequence, its cotranslational nascent
chain elongation rate, and folding.
PMID- 28507160
TI - Emergent magnetism at transition-metal-nanocarbon interfaces.
AB - Charge transfer at metallo-molecular interfaces may be used to design
multifunctional hybrids with an emergent magnetization that may offer an eco
friendly and tunable alternative to conventional magnets and devices. Here, we
investigate the origin of the magnetism arising at these interfaces by using
different techniques to probe 3d and 5d metal films such as Sc, Mn, Cu, and Pt in
contact with fullerenes and rf-sputtered carbon layers. These systems exhibit
small anisotropy and coercivity together with a high Curie point. Low-energy muon
spin spectroscopy in Cu and Sc-C60 multilayers show a quick spin depolarization
and oscillations attributed to nonuniform local magnetic fields close to the
metallo-carbon interface. The hybridization state of the carbon layers plays a
crucial role, and we observe an increased magnetization as sp3 orbitals are
annealed into sp2-pi graphitic states in sputtered carbon/copper multilayers. X
ray magnetic circular dichroism (XMCD) measurements at the carbon K edge of C60
layers in contact with Sc films show spin polarization in the lowest unoccupied
molecular orbital (LUMO) and higher pi*-molecular levels, whereas the dichroism
in the sigma*-resonances is small or nonexistent. These results support the idea
of an interaction mediated via charge transfer from the metal and dz-pi
hybridization. Thin-film carbon-based magnets may allow for the manipulation of
spin ordering at metallic surfaces using electrooptical signals, with potential
applications in computing, sensors, and other multifunctional magnetic devices.
PMID- 28507161
TI - Interleukin-1 and TRAF6-dependent activation of TAK1 in the absence of TAB2 and
TAB3.
AB - Interleukin-1 (IL-1) signaling induces the formation of Lys63-linked ubiquitin
(K63-Ub) chains, which are thought to activate the 'master' protein kinase
TGFbeta-activated kinase 1 (TAK1) by interacting with its TAK1-binding 2 (TAB2)
and TAB3 subunits. Here, we report that IL-1beta can also activate the TAB1-TAK1
heterodimer present in TAB2/TAB3 double knockout (DKO) IL-1 receptor-expressing
cells. The IL-1beta-dependent activation of the TAB1-TAK1 heterodimer in TAB2/3
DKO cells is required for the expression and E3 ligase activity of tumor necrosis
factor receptor-associated factor 6 (TRAF6) and is reduced by the small
interfering RNA (siRNA) knockdown of ubiquitin conjugating 13 (Ubc13), an E2
conjugating enzyme that directs the formation of K63-Ub chains. IL-1beta
signaling was restored to TAB1/2/3 triple KO cells by the re-expression of either
TAB1 or TAB2, but not by an ubiquitin binding-defective mutant of TAB2. We
conclude that IL-1beta can induce the activation of TAK1 in two ways, only one of
which requires the binding of K63-Ub chains to TAB2/3. The early IL-1beta
stimulated, TAK1-dependent activation of p38alpha mitogen-activated protein (MAP)
kinase and the canonical IkappaB kinase (IKK) complex, as well as the NF-kappaB
dependent transcription of immediate early genes, was similar in TAB2/3 DKO cells
and TAB2/3-expressing cells. However, in contrast with TAB2/3-expressing cells,
IL-1beta signaling was transient in TAB2/3 DKO cells, and the activation of c-Jun
N-terminal kinase 1 (JNK1), JNK2 and p38gamma was greatly reduced at all times.
These observations indicate a role for TAB2/3 in directing the TAK1-dependent
activation of MAP kinase kinases that switch on JNK1/2 and p38gamma MAP kinases.
These observations and the transient activation of the TAB1-TAK1 heterodimer may
explain why IL-1beta-dependent IL-8 mRNA formation was abolished in TAB2/3 DKO
cells.
PMID- 28507162
TI - Lipophagy prevents activity-dependent neurodegeneration due to dihydroceramide
accumulation in vivo.
AB - Dihydroceramide desaturases are evolutionarily conserved enzymes that convert
dihydroceramide (dhCer) to ceramide (Cer). While elevated Cer levels cause
neurodegenerative diseases, the neuronal activity of its direct precursor, dhCer,
remains unclear. We show that knockout of the fly dhCer desaturase gene,
infertile crescent (ifc), results in larval lethality with increased dhCer and
decreased Cer levels. Light stimulation leads to ROS increase and apoptotic cell
death in ifc-KO photoreceptors, resulting in activity-dependent
neurodegeneration. Lipid-containing Atg8/LC3-positive puncta accumulate in ifc-KO
photoreceptors, suggesting lipophagy activation. Further enhancing lipophagy
reduces lipid droplet accumulation and rescues ifc-KO defects, indicating that
lipophagy plays a protective role. Reducing dhCer synthesis prevents
photoreceptor degeneration and rescues ifc-KO lethality, while supplementing
downstream sphingolipids does not. These results pinpoint that dhCer accumulation
is responsible for ifc-KO defects. Human dhCer desaturase rescues ifc-KO larval
lethality, and rapamycin reverses defects caused by dhCer accumulation in human
neuroblastoma cells, suggesting evolutionarily conserved functions. This study
demonstrates a novel requirement for dhCer desaturase in neuronal maintenance in
vivo and shows that lipophagy activation prevents activity-dependent degeneration
caused by dhCer accumulation.
PMID- 28507164
TI - Reliability of low-power cycling efficiency in energy expenditure phenotyping of
inactive men and women.
AB - Standardized approaches to assess human energy expenditure (EE) are well defined
at rest and at moderate to high-intensity exercise, but not at light intensity
physical activities energetically comparable with those of daily life (i.e., 1.5
4 times the resting EE, i.e., 1.5-4 METs). Our aim was to validate a graded
exercise test for assessing the energy cost of low-intensity dynamic work in
physically inactive humans, that is, those who habitually do not meet the
guidelines for moderate-to-vigorous aerobic physical activity levels. In healthy
and inactive young men and women (n = 55; aged 18-32 years), EE was assessed in
the overnight-fasted state by indirect calorimetry at rest and during graded
cycling between 5 and 50W for 5 min at each power output on a bicycle ergometer.
Repeatability was investigated on three separate days, and the effect of cadence
was investigated in the range of 40-90 rpm. Within the low power range of
cycling, all subjects perceived the exercise test as "light" on the Borg scale,
the preferred cadence being 60 rpm. A strong linearity of the EE-power
relationship was observed between 10 and 50 W for each individual (r > 0.98), and
the calculation of delta efficiency (DE) from the regression slope indicated that
DE was similar in men and women (~29%). DE showed modest inter-individual
variability with a coefficient of variation (CV) of 11%, and a low intra
individual variability with a CV of ~ 5%. No habituation or learning effect was
observed in DE across days. In conclusion, the assessment of the efficiency of
low power cycling by linear regression - and conducted within the range of EE
observed for low-intensity movements of everyday life (1.5-4 METs) - extends the
capacity for metabolic phenotyping in the inactive population.
PMID- 28507163
TI - Ca2+ binding to F-ATP synthase beta subunit triggers the mitochondrial
permeability transition.
AB - F-ATP synthases convert the electrochemical energy of the H+ gradient into the
chemical energy of ATP with remarkable efficiency. Mitochondrial F-ATP synthases
can also undergo a Ca2+-dependent transformation to form channels with properties
matching those of the permeability transition pore (PTP), a key player in cell
death. The Ca2+ binding site and the mechanism(s) through which Ca2+ can
transform the energy-conserving enzyme into a dissipative structure promoting
cell death remain unknown. Through in vitro, in vivo and in silico studies we (i)
pinpoint the "Ca2+-trigger site" of the PTP to the catalytic site of the F-ATP
synthase beta subunit and (ii) define a conformational change that propagates
from the catalytic site through OSCP and the lateral stalk to the inner membrane.
T163S mutants of the beta subunit, which show a selective decrease in Ca2+-ATP
hydrolysis, confer resistance to Ca2+-induced, PTP-dependent death in cells and
developing zebrafish embryos. These findings are a major advance in the molecular
definition of the transition of F-ATP synthase to a channel and of its role in
cell death.
PMID- 28507165
TI - Reliability and validity of an agility-like incremental exercise test with
multidirectional change-of-direction movements in response to a visual stimulus.
AB - The aim of the study was to evaluate the reliability and validity of
cardiorespiratory and metabolic variables, that is, peak oxygen uptake (V'O2peak)
and heart rate (HRpeak), obtained from an agility-like incremental exercise test
for team sport athletes. To investigate the test-retest reliability, 25 team
sport athletes (age: 22 +/- 3 years, body mass: 75 +/- 7 kg, height: 182 +/- 6
cm) performed an agility-like incremental exercise test on the SpeedCourt (SC)
system incorporating multidirectional change-of-direction (COD) movements twice.
For each step of the incremental SC test, the athletes covered a 40-m distance
interspersed with a 10-sec rest period. Each 40 m distance was split into short
sprints (2.25-6.36 m) separated by multidirectional COD movements (0 degrees -180
degrees ), which were performed in response to an external visual stimulus. All
performance and physiological data were validated with variables obtained from a
ramp-like treadmill and Yo-Yo intermittent recovery level 2 test (Yo-Yo IR2). The
incremental SC test revealed high test-retest reliability for the time to
exhaustion (ICC = 0.85, typical error [TE] = 0.44, and CV% = 3.88), V'O2peak,
HRpeak, ventilation, and breathing frequency (ICC = 0.84, 0.72, 0.89, 0.77,
respectively). The time to exhaustion (r = 0.50, 0.74) of the incremental SC test
as well as the peak values for V'O2 (r = 0.59, 0.52), HR (r = 0.75, 0.78),
ventilation (r = 0.57, 0.57), and breathing frequency (r = 0.68, 0.68) were
significantly correlated (P <= 0.01) with the ramp-like treadmill test and the Yo
Yo IR2, respectively. The incremental SC test represents a reliable and valid
method to assess peak values for V'O2 and HR with respect to the specific demand
of team sport match play by incorporating multidirectional COD movements,
decision making, and cognitive components.
PMID- 28507166
TI - Matrix stiffness regulates migration of human lung fibroblasts.
AB - In patients with pulmonary diseases such as idiopathic pulmonary fibrosis and
severe acute respiratory distress syndrome, progressive pulmonary fibrosis is
caused by dysregulated wound healing via activation of fibroblasts after lung
inflammation or severe damage. Migration of fibroblasts toward the fibrotic
lesions plays an important role in pulmonary fibrosis. Fibrotic tissue in the
lung is much stiffer than normal lung tissue. Emerging evidence supports the
hypothesis that the stiffness of the matrix is not only a consequence of
fibrosis, but also can induce fibroblast activation. Nevertheless, the effects of
substrate rigidity on migration of lung fibroblasts have not been fully
elucidated. We evaluated the effects of substrate stiffness on the morphology,
alpha-smooth muscle actin (alpha-SMA) expression, and cell migration of primary
human lung fibroblasts by using polyacrylamide hydrogels with stiffnesses ranging
from 1 to 50 kPa. Cell motility was assessed by platelet-derived growth factor
(PDGF)-induced chemotaxis and random walk migration assays. As the stiffness of
substrates increased, fibroblasts became spindle-shaped and spread. Expression of
alpha-SMA proteins was higher on the stiffer substrates (25 kPa gel and plastic
dishes) than on the soft 2 kPa gel. Both PDGF-induced chemotaxis and random walk
migration of fibroblasts precultured on stiff substrates (25 kPa gel and plastic
dishes) were significantly higher than those of cells precultured on 2 kPa gel.
Transfection of the fibroblasts with short interfering RNA for alpha-SMA
inhibited cell migration. These findings suggest that fibroblast activation
induced by a stiff matrix is involved in mechanisms of the pathophysiology of
pulmonary fibrosis.
PMID- 28507168
TI - Nutritional interventions and the IL-6 response to exercise.
AB - IL-6 is a pleiotropic cytokine with a wide range of biologic effects. In response
to prolonged exercise, IL-6 is synthesized by contracting skeletal muscle and
released into circulation. Circulating IL-6 is thought to maintain energy status
during exercise by acting as an energy sensor for contracting muscle and
stimulating glucose production. If tissue damage occurs, immune cells infiltrate
and secrete cytokines, including IL-6, to repair skeletal muscle damage. With
adequate rest and nutrition, the IL-6 response to exercise is attenuated as
skeletal muscle adapts to training. However, sustained elevations in IL-6 due to
repeated bouts of unaccustomed activities or prolonged exercise with limited rest
may result in untoward physiologic effects, such as accelerated muscle
proteolysis and diminished nutrient absorption, and may impair normal adaptive
responses to training. Recent intervention studies have explored the role of
mixed meals or carbohydrate, protein, omega-3 fatty acid, or antioxidant
supplementation in mitigating exercise-induced increases in IL-6. Emerging
evidence suggests that sufficient energy intake before exercise is an important
factor in attenuating exercise-induced IL-6 by maintaining muscle glycogen. We
detail various nutritional interventions that may affect the IL-6 response to
exercise in healthy human adults and provide recommendations for future research
exploring the role of IL-6 in the adaptive response to exercise.-Hennigar, S. R.,
McClung, J. P., Pasiakos, S. M. Nutritional interventions and the IL-6 response
to exercise.
PMID- 28507167
TI - Early activation of deleterious molecular pathways in the kidney in experimental
heart failure with atrial remodeling.
AB - Heart failure (HF) is a major health problem with worsening outcomes when renal
impairment is present. Therapeutics for early phase HF may be effective for
cardiorenal protection, however the detailed characteristics of the kidney in
early-stage HF (ES-HF), and therefore treatment for potential renal protection,
are poorly defined. We sought to determine the gene and protein expression
profiles of specific maladaptive pathways of ES-HF in the kidney and heart.
Experimental canine ES-HF, characterized by de-novo HF with atrial remodeling but
not ventricular fibrosis, was induced by right ventricular pacing for 10 days.
Kidney cortex (KC), medulla (KM), left ventricle (LV), and left atrial (LA)
tissues from ES-HF versus normal canines (n = 4 of each) were analyzed using RT
PCR microarrays and protein assays to assess genes and proteins related to
inflammation, renal injury, apoptosis, and fibrosis. ES-HF was characterized by
increased circulating natriuretic peptides and components of the renin
angiotensin-aldosterone system and decreased sodium and water excretion with mild
renal injury and up-regulation of CNP and renin genes in the kidney. Compared to
normals, widespread genes, especially genes of the inflammatory pathways, were up
regulated in KC similar to increases seen in LA Protein expressions related to
inflammatory cytokines were also augmented in the KC Gene and protein changes
were less prominent in the LV and KM The ES-HF displayed mild renal injury with
widespread gene changes and increased inflammatory cytokines. These changes may
provide important clues into the pathophysiology of ES-HF and for therapeutic
molecular targets in the kidney of ES-HF.
PMID- 28507169
TI - Human neutrophil elastase induces endothelial cell apoptosis by activating the
PERK-CHOP branch of the unfolded protein response.
AB - Human neutrophil elastase impacts on atherosclerotic plaque stability by inducing
apoptosis in endothelial cells. Our aim was to investigate the proapoptotic
mechanism of elastase on endothelial cells and to evaluate the presence of
elastase in human plaque material. Human endothelial cells were treated with
purified human neutrophil elastase. Apoptosis was assayed by capsase-3/7
activation, TUNEL, and sub-G1 assay. Activation of unfolded protein response
(UPR) effector molecules binding Ig protein, soluble X-binding protein-1, protein
kinase RNA-like ER kinase (PERK), and C/EBP-homologous protein (CHOP) was
analyzed by RT-PCR, immunocytochemistry, and Western blot. Genetic silencing of
CHOP was achieved by small interfering RNA. Elastase induces autophagic-apoptotic
forms of endothelial cell death in a time- and dose-dependent manner, in
conjunction with a significant increase in phosphorylation/expression of the
canonical UPR-activation markers PERK and CHOP. By using CHOP knockdown, we
identified CHOP as a key mediator of elastase-induced endothelial cell death.
Immunohistochemical analysis of human rupture-prone plaque specimens confirmed
the presence of elastase and colocalization with apoptosis. We have demonstrated
for the first time that the PERK-CHOP branch of the UPR is causally involved in
elastase-induced apoptosis of endothelial cells. Ex vivo analysis of human
rupture-prone plaques confirmed the presence of elastase and its colocalization
with markers of apoptosis. This novel role of elastase underlines the potential
of combined targeting of elastase and endoplasmic reticulum stress in the
prevention of plaque progression and cardiovascular events.-Grechowa, I., Horke,
S., Wallrath, A., Vahl, C.-F., Dorweiler, B. Human neutrophil elastase induces
endothelial cell apoptosis by activating the PERK-CHOP branch of the unfolded
protein response.
PMID- 28507170
TI - Hypertension-Causing Mutation in Peroxisome Proliferator-Activated Receptor gamma
Impairs Nuclear Export of Nuclear Factor-kappaB p65 in Vascular Smooth Muscle.
AB - Selective expression of dominant negative (DN) peroxisome proliferator-activated
receptor gamma (PPARgamma) in vascular smooth muscle cells (SMC) results in
hypertension, atherosclerosis, and increased nuclear factor-kappaB (NF-kappaB)
target gene expression. Mesenteric SMC were cultured from mice designed to
conditionally express wild-type (WT) or DN-PPARgamma in response to Cre
recombinase to determine how SMC PPARgamma regulates expression of NF-kappaB
target inflammatory genes. SMC-specific overexpression of WT-PPARgamma or agonist
induced activation of endogenous PPARgamma blunted tumor necrosis factor alpha
(TNF-alpha)-induced NF-kappaB target gene expression and activity of an NF-kappaB
responsive promoter. TNF-alpha-induced gene expression responses were enhanced by
DN-PPARgamma in SMC. Although expression of NF-kappaB p65 was unchanged, nuclear
export of p65 was accelerated by WT-PPARgamma and prevented by DN-PPARgamma in
SMC. Leptomycin B, a nuclear export inhibitor, blocked p65 nuclear export and
inhibited the anti-inflammatory action of PPARgamma. Consistent with a role in
facilitating p65 nuclear export, WT-PPARgamma coimmunoprecipitated with p65, and
WT-PPARgamma was also exported from the nucleus after TNF-alpha treatment.
Conversely, DN-PPARgamma does not bind to p65 and was retained in the nucleus
after TNF-alpha treatment. Transgenic mice expressing WT-PPARgamma or DN
PPARgamma specifically in SMC (S-WT or S-DN) were bred with mice expressing
luciferase controlled by an NF-kappaB-responsive promoter to assess effects on NF
kappaB activity in whole tissue. TNF-alpha-induced NF-kappaB activity was
decreased in aorta and carotid artery from S-WT but was increased in vessels from
S-DN mice. We conclude that SMC PPARgamma blunts expression of proinflammatory
genes by inhibition of NF-kappaB activity through a mechanism promoting nuclear
export of p65, which is abolished by DN mutation in PPARgamma.
PMID- 28507173
TI - Resistant Hypertension: An Update of Experimental and Clinical Findings.
PMID- 28507174
TI - Elevated Adenosine Induces Placental DNA Hypomethylation Independent of A2B
Receptor Signaling in Preeclampsia.
AB - Preeclampsia is a prevalent pregnancy hypertensive disease with both maternal and
fetal morbidity and mortality. Emerging evidence indicates that global placental
DNA hypomethylation is observed in patients with preeclampsia and is linked to
altered gene expression and disease development. However, the molecular basis
underlying placental epigenetic changes in preeclampsia remains unclear. Using 2
independent experimental models of preeclampsia, adenosine deaminase-deficient
mice and a pathogenic autoantibody-induced mouse model of preeclampsia, we
demonstrate that elevated placental adenosine not only induces hallmark features
of preeclampsia but also causes placental DNA hypomethylation. The use of genetic
approaches to express an adenosine deaminase minigene specifically in placentas,
or adenosine deaminase enzyme replacement therapy, restored placental adenosine
to normal levels, attenuated preeclampsia features, and abolished placental DNA
hypomethylation in adenosine deaminase-deficient mice. Genetic deletion of CD73
(an ectonucleotidase that converts AMP to adenosine) prevented the elevation of
placental adenosine in the autoantibody-induced preeclampsia mouse model and
ameliorated preeclampsia features and placental DNA hypomethylation.
Immunohistochemical studies revealed that elevated placental adenosine-mediated
DNA hypomethylation predominantly occurs in spongiotrophoblasts and labyrinthine
trophoblasts and that this effect is independent of A2B adenosine receptor
activation in both preeclampsia models. Extending our mouse findings to humans,
we used cultured human trophoblasts to demonstrate that adenosine functions
intracellularly and induces DNA hypomethylation without A2B adenosine receptor
activation. Altogether, both mouse and human studies reveal novel mechanisms
underlying placental DNA hypomethylation and potential therapeutic approaches for
preeclampsia.
PMID- 28507171
TI - First-in-Man Demonstration of Direct Endothelin-Mediated Natriuresis and
Diuresis.
AB - Endothelin (ET) receptor antagonists are potentially novel therapeutic agents in
chronic kidney disease and resistant hypertension, but their use is complicated
by sodium and water retention. In animal studies, this side effect arises from
ETB receptor blockade in the renal tubule. Previous attempts to determine whether
this mechanism operates in humans have been confounded by the hemodynamic
consequences of ET receptor stimulation/blockade. We aimed to determine the
effects of ET signaling on salt transport in the human nephron by administering
subpressor doses of the ET-1 precursor, big ET-1. We conducted a 2-phase
randomized, double-blind, placebo-controlled crossover study in 10 healthy
volunteers. After sodium restriction, subjects received either intravenous
placebo or big ET-1, in escalating dose (<=300 pmol/min). This increased plasma
concentration and urinary excretion of ET-1. Big ET-1 reduced heart rate (~8
beats/min) but did not otherwise affect systemic hemodynamics or glomerular
filtration rate. Big ET-1 increased the fractional excretion of sodium (from 0.5
to 1.0%). It also increased free water clearance and tended to increase the
abundance of the sodium-potassium-chloride cotransporter (NKCC2) in urinary
extracellular vesicles. Our protocol induced modest increases in circulating and
urinary ET-1. Sodium and water excretion increased in the absence of significant
hemodynamic perturbation, supporting a direct action of ET-1 on the renal tubule.
Our data also suggest that sodium reabsorption is stimulated by ET-1 in the thick
ascending limb and suppressed in the distal renal tubule. Fluid retention
associated with ET receptor antagonist therapy may be circumvented by
coprescribing potassium-sparing diuretics.
PMID- 28507172
TI - Hemodynamic and Mechanical Properties of the Proximal Aorta in Young and Middle
Aged Adults With Isolated Systolic Hypertension: The Dallas Heart Study.
AB - The aim of this study was to assess characteristic impedance (Zc) of the proximal
aorta in young and middle-aged individuals with isolated systolic hypertension
(ISH). Zc is an index of aortic stiffness relative to aortic size. In the Dallas
Heart Study, 2001 untreated participants 18 to 64 years of age (mean age: 42.3
years; 44% black race) were divided into the following groups based on office
blood pressure (BP) measurements: (1) optimal BP (systolic BP [SBP] <120 mm Hg
and diastolic BP [DBP] <80 mm Hg; n=837); (2) prehypertension (SBP 120-139 mm Hg
and DBP 80-89 mm Hg; n=821); (3) ISH (SBP >=140 mm Hg and DBP <90 mm Hg; n=121);
(4) isolated diastolic hypertension (SBP <140 mm Hg and DBP >=90 mm Hg; n=44);
and (5) systolic-diastolic hypertension (SBP >=140 mm Hg and DBP >=90 mm Hg;
n=178). Zc, aortic arch pulse wave velocity, and minimum ascending aortic size
were quantified using cardiovascular magnetic resonance. In multivariable
adjusted linear models, Zc was highest in the ISH group compared with the optimal
BP, isolated diastolic hypertension, or systolic-diastolic hypertension groups
(103.2+/-4.0 versus 68.3+/-2.1, 75.4+/-6.0, and 88.9+/-4.8 dyne*seconds/cm5,
respectively; all P<0.05). The Zc-ISH association did not differ by race. Aortic
pulse wave velocity was highest in the ISH group compared with the optimal BP,
isolated diastolic hypertension, or systolic-diastolic hypertension groups (6.3+/
0.3 versus 4.3+/-0.1, 4.4+/-0.4 and 5.5+/-0.3 m/s, respectively; all P<0.05),
whereas aortic size was similar across groups (all P>0.2). Results were similar
in a subgroup of 1551 participants 18 to 49 years of age. In a multiracial
population-based sample, we found evidence of a mismatch between proximal aortic
stiffness and diameter in young and middle-aged adults with ISH.
PMID- 28507175
TI - A Mutation in the bHLH Domain of the SPCH Transcription Factor Uncovers a BR
Dependent Mechanism for Stomatal Development.
AB - The asymmetric cell divisions necessary for stomatal lineage initiation and
progression in Arabidopsis (Arabidopsis thaliana) require the function of the
basic helix-loop-helix (bHLH) transcription factor SPEECHLESS (SPCH). Mutants
lacking SPCH do not produce stomata or lineages. Here, we isolated a new spch-5
allele carrying a point mutation in the bHLH domain that displayed normal growth,
but had an extremely low number of sometimes clustered stomata in the leaves,
whereas the hypocotyls did not have any stomata. In vivo tracking of leaf
epidermal cell divisions, combined with marker lines and genetic analysis, showed
that the spch-5 leaf phenotype is dosage dependent and results from the decreased
ability to initiate and amplify lineages, defects in asymmetric cell fate
allocation, and misorientation of asymmetric division planes. Notably,
application of brassinosteroids (BRs) partly rescued the stomatal leaf phenotype
of spch-5 Transcriptomic analysis combining spch-5 with BR treatments revealed
that the expression of a set of SPCH target genes was restored by BRs. Our
results also show that BR-dependent stomata formation and expression of some, but
not all, SPCH target genes require the integrity of the bHLH domain of SPCH.
PMID- 28507176
TI - BTS guideline for oxygen use in adults in healthcare and emergency settings.
PMID- 28507177
TI - Evidence for a Derangement of the Microvascular System in Patients with a Very
Early Diagnosis of Systemic Sclerosis.
AB - OBJECTIVE: To investigate whether patients with a very early diagnosis of
systemic sclerosis (VEDOSS) may already present circulating markers and in vitro
signs of microvascular dysfunction. METHODS: Serum samples were obtained from 55
patients with systemic sclerosis (SSc), 25 patients with VEDOSS, and 55 matched
healthy controls (HC). Serum levels of pan-vascular endothelial growth factor
(VEGF) and soluble neuropilin-1 (sNRP-1) were measured by ELISA. Human dermal
microvascular endothelial cells (H-MVEC) were cultured and stimulated with SSc,
VEDOSS, and HC sera. Protein expression of NRP-1 was analyzed by Western
blotting, cell proliferation by 5'-bromodeoxyuridine assay, migration capacity by
wound-healing assay, and capillary-like tube formation by Matrigel assay.
RESULTS: Serum levels of pan-VEGF were increased in patients with VEDOSS and SSc
versus HC (p = 0.05 and p = 0.003, respectively). Serum levels of sNRP-1 were
significantly reduced in patients with VEDOSS and SSc compared with controls (p =
0.012 and p = 0.027, respectively). NRP-1 expression was decreased in H-MVEC
stimulated with VEDOSS sera (p < 0.001 vs HC). Proliferation was reduced in H
MVEC stimulated either with VEDOSS or SSc sera in comparison with HC sera (p =
0.015 and p = 0.043, respectively). Wound healing was compromised in H-MVEC
stimulated with VEDOSS and SSc sera versus HC sera (p < 0.01 for both).
Capillarogenesis was decreased in H-MVEC stimulated with VEDOSS sera (p < 0.01)
and SSc sera (p < 0.001) compared with cells stimulated with HC sera. CONCLUSION:
Similar to patients with SSc, patients with VEDOSS already present biological
signs of endothelial dysfunction. Our data demonstrate that VEDOSS sera
significantly modify endothelial cell behavior and impair the angiogenic
potential of the microvascular system.
PMID- 28507178
TI - Anti-carbamylated Protein Antibodies Are Detectable in Various Connective Tissue
Diseases.
AB - OBJECTIVE: Anti-carbamylated protein (anti-CarP) antibodies are possible
diagnostic biomarkers of anticitrullinated protein antibody (ACPA)-negative
rheumatoid arthritis (RA). We aimed to elucidate the prevalence of anti-CarP
antibodies in non-RA connective tissue diseases (CTD) because CTD are important
in the differential diagnosis of ACPA-negative RA. METHODS: The sera from 266
patients with RA and 616 patients with CTD and 80 healthy controls were examined
using an in-house anti-CarP ELISA. RESULTS: The prevalence and the level of anti
CarP antibodies in several CTD were comparable to those in ACPA-negative RA.
CONCLUSION: Anti-CarP antibodies are not useful for differentiating ACPA-negative
RA from CTD.
PMID- 28507180
TI - Outcome Measures Used in Arthroplasty Trials: Systematic Review of the 2008 and
2013 Literature.
AB - OBJECTIVE: Previously published literature assessing the reporting of outcome
measures used in joint replacement randomized controlled trials (RCT) has
revealed disappointing results. It remains unknown whether international
initiatives have led to any improvement in the quality of reporting and/or a
reduction in the heterogeneity of outcome measures used. Our objective was to
systematically assess and compare primary outcome measures and the risk of bias
in joint replacement RCT published in 2008 and 2013. METHODS: We searched
MEDLINE, EMBASE, and CENTRAL for RCT investigating adult patients undergoing
joint replacement surgery. Two authors independently identified eligible trials,
extracted data, and assessed risk of bias using the Cochrane tool. RESULTS:
Seventy RCT (30 in 2008, 40 in 2013) met the eligibility criteria. There was no
significant difference in the number of trials judged to be at low overall risk
of bias (n = 6, 20%) in 2008 compared with 2013 [6 (15%); chi-square = 0.302, p =
0.75]. Significantly more trials published in 2008 did not specify a primary
outcome measure (n = 25, 83%) compared with 18 trials (45%) in 2013 (chi-square =
10.6316, p = 0.001). When specified, there was significant heterogeneity in the
measures used to assess primary outcomes. CONCLUSION: While less than a quarter
of trials published in both 2008 and 2013 were judged to be at low overall risk
of bias, significantly more trials published in 2013 specified a primary outcome.
Although this might represent a temporal trend toward improvement, the overall
frequency of primary outcome reporting and the wide heterogeneity in primary
outcomes reported remain suboptimal.
PMID- 28507179
TI - Elevated Expression of the NLRP3 Inflammasome and Its Correlation with Disease
Activity in Adult-onset Still Disease.
AB - OBJECTIVE: The dysregulation of the NLRP3 (NLR containing a pyrin domain)
inflammasome is involved in autoinflammatory diseases. Adult-onset Still disease
(AOSD) is regarded as an autoinflammatory disease. However, the pathogenic
involvement of NLRP3 inflammasome in AOSD remains unclear and NLRP3 activators in
AOSD are currently unknown. METHODS: The mRNA expression of NLRP3 inflammasome
signaling in peripheral blood mononuclear cells (PBMC) from 34 patients with AOSD
and 14 healthy subjects was determined using quantitative-PCR (qPCR). The changes
in mRNA and protein levels of NLRP3 inflammasome signaling in PBMC treated with
the potential activator [imiquimod (IMQ)] or inhibitor of NLRP3 were evaluated
using qPCR and immunoblotting, respectively. The supernatant levels of
interleukin (IL)-1beta and IL-18 were determined by ELISA. RESULTS: Significantly
higher mRNA levels of NLRP3 inflammasome signaling were observed in patients with
AOSD compared with healthy controls. NLRP3 expressions were positively correlated
with disease activity in patients with AOSD. IMQ (an effective Toll-like receptor
7 ligand; 10 ug/ml and 25 ug/ml) stimulation of PBMC from patients with AOSD
induced dose-dependent increases of mRNA expression of NLRP3 (mean +/- standard
error of the mean, 2.06 +/- 0.46 and 6.05 +/- 1.84, respectively), caspase-1
(1.81 +/- 0.23 and 4.25 +/- 0.48), IL-1beta (5.68 +/- 1.51 and 12.13 +/- 3.71),
and IL-18 (2.32 +/- 0.37 and 4.81 +/- 0.51) compared with controls (all p <
0.005). IMQ stimulation of PBMC from patients similarly induced greater increases
in protein expressions of NLRP3 inflammasome compared with controls. The protein
expressions of NLRP3, IL-1beta, and IL-18 on PBMC significantly decreased after
treatment with NLRP3 inhibitor in patients with AOSD. CONCLUSION: Increased
expression of NLRP3 inflammasome and its positive correlation with disease
activity in AOSD suggest its involvement in disease pathogenesis. IMQ upregulated
expressions of NLRP3 inflammasome signaling, and IMQ might be an activator of
NLRP3 inflammasome in AOSD.
PMID- 28507181
TI - Fli1 Deficiency Induces CXCL6 Expression in Dermal Fibroblasts and Endothelial
Cells, Contributing to the Development of Fibrosis and Vasculopathy in Systemic
Sclerosis.
AB - OBJECTIVE: CXCL6, a chemokine with proangiogenic property, is reported to be
involved in vasculopathy associated with systemic sclerosis (SSc). We
investigated the contribution of CXCL6 to SSc development by focusing on the
association of friend leukemia virus integration 1 (Fli1) deficiency, a potential
predisposing factor of SSc, with CXCL6 expression and clinical correlation of
serum CXCL6 levels. METHODS: mRNA levels of target genes and the binding of Fli1
to the CXCL6 promoter were evaluated by quantitative reverse transcription-PCR
and chromatin immunoprecipitation, respectively. Serum CXCL6 levels were
determined by ELISA. RESULTS: FLI1 siRNA significantly enhanced CXCL6 mRNA
expression in human dermal fibroblasts and human dermal microvascular endothelial
cells, while Fli1 haploinsufficiency significantly suppressed CXCL6 mRNA
expression in murine peritoneal macrophages stimulated with lipopolysaccharide.
Supporting a critical role of Fli1 deficiency to induce SSc-like phenotypes,
CXCL6 mRNA expression was higher in SSc dermal fibroblasts than in normal dermal
fibroblasts. Importantly, Fli1 bound to the CXCL6 promoter in dermal fibroblasts,
endothelial cells, and THP-1 cells. In patients with SSc, serum CXCL6 levels
correlated positively with the severity of dermal and pulmonary fibrosis and were
elevated in association with cardiac and pulmonary vascular involvement and
cutaneous vascular symptoms, including Raynaud phenomenon, digital ulcers
(DU)/pitting scars, and telangiectasia. Especially, serum CXCL6 levels were
associated with DU/pitting scars and heart involvement by multiple regression
analysis. CONCLUSION: CXCL6 expression is upregulated by Fli1 deficiency in
fibroblasts and endothelial cells, potentially contributing to the development of
fibrosis and vasculopathy in the skin, lung, and heart of SSc.
PMID- 28507182
TI - Association between Dairy Product Consumption and Incidence of Total Hip
Arthroplasty for Osteoarthritis.
AB - OBJECTIVE: The aim of this prospective cohort study was to determine whether
dairy product consumption was associated with the incidence of total hip
arthroplasty for osteoarthritis (OA). METHODS: There were 38,924 participants
from the Melbourne Collaborative Cohort Study who had dairy product consumption
recorded in 1990-1994. The incidence of total hip arthroplasty for OA during 2001
2013 was determined by linking cohort records to the Australian Orthopaedic
Association National Joint Replacement Registry. RESULTS: Over an average of 11.8
years of followup, 1505 total hip arthroplasties for OA were identified (524 in
men, 981 in women). In men, a 1 SD increase in dairy product consumption was
associated with a 21% increased incidence of total hip arthroplasty for OA (HR
1.21, 95% CI 1.10-1.33), with a dose-response relationship observed for quartiles
of dairy product consumption (p for trend = 0.001). These results were
independent of age, body mass index, country of birth, education, smoking status,
vigorous physical activity, calcium supplementation, energy consumption,
circulating 25-hydroxy vitamin D, hypertension, and diabetes. No significant
association was observed for women (HR 1.02, 95% CI 0.95-1.09). CONCLUSION:
Increasing dairy product consumption was associated with an increased risk of
total hip arthroplasty for men with OA, with no significant association observed
for women. Understanding the mechanisms may help identify strategies to prevent
hip OA, particularly for men.
PMID- 28507183
TI - Longterm Hydroxychloroquine Therapy and Low-dose Aspirin May Have an Additive
Effectiveness in the Primary Prevention of Cardiovascular Events in Patients with
Systemic Lupus Erythematosus.
AB - OBJECTIVE: Systemic lupus erythematosus (SLE) is associated with an increased
risk of cardiovascular disease (CVD). Thromboprophylaxis with low-dose aspirin
(ASA) and hydroxychloroquine (HCQ) seems promising in SLE. We investigated the
effects of HCQ cumulative dosages (c-HCQ) and the possible synergistic efficacy
of ASA and HCQ in preventing a first CV event (CVE) in patients with SLE.
METHODS: Patients consecutively admitted to our center who, at admission,
satisfied the 1997 American College of Rheumatology and/or 2012 Systemic Lupus
Collaborating Clinics classification criteria for SLE, and had not experienced
any CVE, were enrolled. The occurrence of a thrombotic event, use of ASA, and c
HCQ were recorded. Kaplan-Meier analysis was performed to determine the c-HCQ
associated with a lower incidence of CVE. Cox regression analysis served to
identify factors associated with a first CVE. RESULTS: For the study, 189
patients with SLE were enrolled and monitored for 13 years (median). Ten CVE
occurred during followup. At Kaplan-Meier analysis, the CVE-free rate was higher
in ASA-treated patients administered a c-HCQ > 600 g (standard HCQ dose for at
least 5 yrs) than in patients receiving ASA alone, or with a c-HCQ dose < 600 g
(log-rank test chi-square = 4.01, p = 0.04). Multivariate analysis showed that
antimalarials plus ASA protected against thrombosis (HR 0.041 and HR 0.047,
respectively), while antiphospholipid antibodies (HR 17.965) and hypertension (HR
18.054) increased the risk of a first CVE. CONCLUSION: Our results suggest that
prolonged use of HCQ plus ASA is thromboprotective in SLE and provides additional
evidence for its continued use in patients with SLE.
PMID- 28507184
TI - Importance of Obtaining Remission for Work Productivity and Activity of Patients
with Rheumatoid Arthritis.
AB - OBJECTIVE: To identify the factors relevant to work and activity impairment in
patients with rheumatoid arthritis. METHODS: In total, 1274 consecutive patients
were included. Work and activity impairment were measured by the Work
Productivity and Activity Impairment questionnaire, and related clinical factors
were examined. RESULTS: Work and activity impairment was reported by 67.4% of the
patients. Multivariable linear regression analyses revealed pain and non
remission to be associated with activity impairment and presenteeism. Patients in
remission had significantly less activity impairment and presenteeism than those
with low disease activity. CONCLUSION: Remission achievement is essential for
ensuring work performance and activity.
PMID- 28507186
TI - Zygapophyseal Joint Fusion in Ankylosing Spondylitis Assessed by Computed
Tomography: Associations with Syndesmophytes and Spinal Motion.
AB - OBJECTIVE: Because zygapophyseal joints (ZJ) are difficult to visualize on
radiographs, little is known about the relationship of ZJ fusion to other
features of spinal damage in ankylosing spondylitis (AS). We used computed
tomography (CT) to investigate the concordance of ZJ fusion and syndesmophytes,
and examined the contribution of both features to spinal motion. METHODS: We
performed thoracolumbar CT scans (T10-T11 to L3-L4) on 55 patients. Two readers
scored scans for ZJ fusion, which were compared to syndesmophyte height and
extent of bridging, measured by computer algorithm at the same levels. We used
multiple regression analysis to evaluate the relative contributions of ZJ fusion
and syndesmophytes to spinal mobility. RESULTS: Fifty-one percent of patients had
ZJ fusion in at least 1 vertebral level. Fusion was present in 129 of 652
individual ZJ. Syndesmophytes and bridging were often present in vertebral levels
without ZJ fusion, suggesting that syndesmophytes most often develop first. ZJ
fusion was present in 34% of vertebral levels with syndesmophytes and 55.9% of
levels with bridging, suggesting a closer association with bridging.
Syndesmophytes and ZJ fusion had similar associations with the modified Schober
test, but syndesmophytes were more strongly associated with limitations in
lateral thoracolumbar flexion. ZJ rarely showed new fusion over 4 years.
CONCLUSION: Thoracolumbar ZJ fusion in AS is rarely present at vertebral levels
without syndesmophytes. Syndesmophytes, therefore, likely appear before ZJ fusion
at a given vertebral level. Both syndesmophytes and ZJ fusion contribute to
limited forward lumbar flexion, but syndesmophytes contribute more to limited
lateral flexion.
PMID- 28507185
TI - The OMERACT First-time Participant Program: Fresh Eye from the New Guys.
AB - OBJECTIVE: To describe the experience of the first-time participant (newbie)
training program at the Outcome Measures in Rheumatology (OMERACT) 2016 meeting.
METHODS: We conducted new participant sessions at OMERACT 2016, including a 2-h
introductory session on Day 1 followed by 1-h evening followup sessions on days 1
4. Pre- and post-meeting surveys assessed participants' levels of comfort with
the principles of the OMERACT Filter 2.0 (the essential tools for OMERACT
methodology) and the different types of OMERACT sessions, and whether
participants felt welcome. In addition, on the final day, a nominal group
technique was used to elicit problematic components of the meeting and to develop
solutions to those problems. RESULTS: Of the 43 new attendees, 38 participated in
the introductory session and 14-18 attended the followup sessions. Comparing Day
1 (preintroductory session) to days 1-3 (post), a similar proportion understood
different types of sessions extremely well [45% (pre) versus 47%, 44%, and 36%
(post), respectively], and a higher proportion understood principles of the
OMERACT filter extremely well [22% (pre) versus 55%, 44%, and 40% (post),
respectively]. Most reported feeling welcome (86.7%) and felt they contributed to
breakout sessions (93.3%) on the evening of Day 1; results were sustained on days
2-3. The most commonly reported "best" experience included the OMERACT culture
and the most common reported experience needing improvement included facilitation
issues during breakouts. CONCLUSION: The first-time participants came to OMERACT
2016 with a high baseline level of understanding. They rapidly attained a high
comfort level with participation and provided concrete and innovative solutions
to the most commonly reported experiences needing improvement.
PMID- 28507187
TI - Measuring Disease Exacerbation and Flares in Rheumatoid Arthritis: Comparison of
Commonly Used Disease Activity Indices and Individual Measures.
AB - OBJECTIVE: To evaluate and compare the utility of commonly used outcome measures
for assessing disease exacerbation or flare in patients with rheumatoid arthritis
(RA). METHODS: Data from the Dutch Potential Optimalisation of (Expediency) and
Effectiveness of Tumor necrosis factor-alpha blockers (POET) study, in which 462
patients discontinued their tumor necrosis factor-alpha inhibitor, were used. The
ability of different measures to discriminate between those with and without
physician-reported flare or medication escalation at the 3-month visit (T2) was
evaluated by calculating effect size (ES) statistics. Responsiveness to increased
disease activity was compared between measures by standardizing change scores
(SCS) from baseline to the 3-month visit. Finally, the incremental validity of
individual outcome measures beyond the Simplified Disease Activity Score was
evaluated using logistic regression analysis. RESULTS: The SCS were greater for
disease activity indices than for any of the individual measures. The 28-joint
Disease Activity Score, Clinical Disease Activity Index, and Simplified Disease
Activity Index performed similarly. Pain and physician's (PGA) and patient's
global assessment (PtGA) of disease activity were the most responsive individual
measures. Similar results were obtained for discriminative ability, with greatest
ES for disease activity indices followed by pain, PGA, and PtGA. Pain was the
only measure to demonstrate incremental validity beyond SDAI in predicting 3
month flare status. CONCLUSION: These results support the use of composite
disease activity indices, patient-reported pain and disease activity, and
physician-reported disease activity for measuring disease exacerbation or
identifying flares of RA. Physical function, acute-phase response, and the
auxiliary measures fatigue, participation, and emotional well-being performed
poorly.
PMID- 28507188
TI - Cryoglobulinemia in Sjogren Syndrome: A Disease Subset that Links Higher Systemic
Disease Activity, Autoimmunity, and Local B Cell Proliferation in Mucosa
associated Lymphoid Tissue.
AB - OBJECTIVE: To compare systemic disease activity by validated tools, i.e., the
European League Against Rheumatism Sjogren Syndrome Disease Activity Index
(ESSDAI) and the Clinical ESSDAI (ClinESSDAI) scores, between primary Sjogren
syndrome (pSS) with positive serum cryoglobulins and pSS without serum
cryoglobulins. METHODS: There were 825 consecutive patients with pSS who were
retrospectively evaluated. RESULTS: The ESSDAI and the ClinESSDAI scores were
significantly higher in cryoglobulin-positive patients (p < 0.0001, for both
scores). Cryoglobulinemia was significantly associated with these domains:
constitutional (p = 0.003), lymphadenopathy (p = 0.007), glandular (p = 0.0002),
cutaneous (p < 0.0001), peripheral nervous system (p < 0.0001), hematological (p
= 0.004), and biological (p < 0.0001). CONCLUSION: Cryoglobulin-positive patients
show the highest systemic activity in pSS.
PMID- 28507189
TI - Oxidative stress affects sperm performance and ejaculate redox status in
subordinate house sparrows.
AB - Oxidative stress is the result of random cellular damage caused by reactive
oxygen species that leads to cell death, ageing or illness. Most physiological
processes can result in oxidative stress, which in turn has been identified as a
major cause of infertility. In promiscuous species, the fertilizing ability of
the ejaculate partly determines the male reproductive success. When dominance
determines access to fertile females, theory predicts that lower ranking males
should increase resource investment into enhancing ejaculate quality. We
hypothesized that subordinate males should thus prioritize antioxidant protection
of their ejaculates to protect them from oxidative stress. We put this hypothesis
to the test by chronically dosing wild house sparrows with diquat (~1 mg kg-1), a
herbicide that increases pro-oxidant generation. We found that, although they
increased their antioxidant levels in the ejaculate, diquat-treated males
produced sperm with reduced velocity. Importantly, and contrary to our
hypothesis, males at the bottom of the hierarchy suffered the largest reduction
in sperm velocity. We suggest that resource access hinders individuals' ability
to cope with environmental hazards. Our results point at oxidative stress as a
likely physiological mechanism mediating ejaculate quality, while individual
ability to access resources may play a role in constraining the extent to which
such resources can be allocated into the ejaculate.
PMID- 28507190
TI - The effect of thermal acclimation on aerobic scope and critical swimming speed in
Atlantic salmon, Salmo salar.
AB - The Atlantic salmon is extensively studied owing to conservation concerns and its
economic importance in aquaculture. However, a thorough report of their aerobic
capacity throughout their entire thermal niche has not been described. In this
study, Atlantic salmon (~450 g) were acclimated for 4 weeks at 3, 8, 13, 18 or 23
degrees C, and then tested in a large Brett-type swimming respirometer in groups
of 10 per trial. Both standard metabolic rate and active metabolic rate continued
to increase with temperature, which resulted in an aerobic scope that also
increased with temperature, but was statistically similar between 13, 18 and 23
degrees C. The critical swimming speed peaked at 18 degrees C (93.1+/-1.2 cm s
1), and decreased significantly at the extreme temperatures to 74.8+/-0.5 and
84.8+/-1.6 cm s-1 at 3 and 23 degrees C, respectively. At 23 degrees C, the
accumulated mortality reached 20% over 4 weeks, while no fish died during
acclimation at colder temperatures. Furthermore, fish at 23 degrees C had poor
appetite and lower condition factor despite still having a high aerobic scope,
suggesting that oxygen uptake was not the limiting factor in the upper thermal
niche boundary. In conclusion, Atlantic salmon were able to maintain a high
aerobic capacity and good swimming capabilities throughout the entire thermal
interval tested, thus demonstrating a high level of flexibility in respiratory
capacity towards different temperature exposures.
PMID- 28507191
TI - Lowering metabolic rate mitigates muscle atrophy in western fence lizards.
AB - Extended periods of skeletal muscle disuse can cause a significant loss of
contractile proteins, which compromises the ability to generate force, mechanical
work or power, thus compromising locomotor performance. Several hibernating
organisms can resist muscle atrophy despite months of inactivity. This resistance
has been attributed to a reduction in body temperature and metabolic rate and
activation of physiological pathways that counteract pathways of protein
degradation. However, in these systems, such strategies are not mutually
exclusive and the effects of these mechanisms can be difficult to separate. In
this study, we used the western fence lizard, Sceloporus occidentalis, as an
ectothermic model to determine whether a reduction in metabolic rate is
sufficient to resist muscle atrophy. We induced atrophy through sciatic
denervation of the gastrocnemius muscle and housed lizards at either 15 or 30
degrees C for 6-7 weeks. Following treatment, we used muscle ergometry to measure
maximum isometric force, the force-velocity relationship and contractile dynamics
in the gastrocnemius. This approach allowed us to relate changes in the size and
morphology to functional metrics of contractile performance. A subset of samples
was used to histologically determine muscle fiber types. At 30 degrees C,
denervated muscles had a larger reduction in muscle mass, physiological cross
sectional area and maximum isometric force than at 15 degrees C. Maximum
shortening velocity of the muscle decreased slightly in animals housed at 30
degrees C but did not change in those housed at 15 degrees C. Our results suggest
that metabolic rate alone can influence the rate of muscle atrophy and that
ectothermic vertebrates may have an intrinsic mechanism to resist muscle atrophy
during seasonal periods of inactivity.
PMID- 28507192
TI - Performance Fatigability: Mechanisms and Task Specificity.
AB - Performance fatigability is characterized as an acute decline in motor
performance caused by an exercise-induced reduction in force or power of the
involved muscles. Multiple mechanisms contribute to performance fatigability and
originate from neural and muscular processes, with the task demands dictating the
mechanisms. This review highlights that (1) inadequate activation of the
motoneuron pool can contribute to performance fatigability, and (2) the demands
of the task and the physiological characteristics of the population assessed,
dictate fatigability and the involved mechanisms. Examples of task and population
differences in fatigability highlighted in this review include contraction
intensity and velocity, stability and support provided to the fatiguing limb, sex
differences, and aging. A future challenge is to define specific mechanisms of
fatigability and to translate these findings to real-world performance and
exercise training in healthy and clinical populations across the life span.
PMID- 28507193
TI - Current and Future Prospects for Preventing Malaria Transmission via the Use of
Insecticides.
AB - Malaria vectors have developed resistance to all classes of insecticides that are
used to target the adult mosquito to prevent parasite transmission. The number of
resistant mosquito populations has increased dramatically in recent years, most
likely as a result of the scale-up of vector control activities, and the
intensity of this resistance is increasing rapidly and compromising the
performance of vector control tools. Bednets and indoor residual spray
formulations containing alternative active ingredients have shown promise in
field trials but are still several years away from implementation. As existing
insecticides become less effective at killing mosquitoes in the countries with
the highest burden of malaria, there is growing concern that the advances made in
reducing malaria transmission will be eroded by insecticide resistance. The
likelihood of this scenario, and strategies that may help mitigate against this,
are reviewed below.
PMID- 28507194
TI - Molecular Basis of Exercise-Induced Skeletal Muscle Mitochondrial Biogenesis:
Historical Advances, Current Knowledge, and Future Challenges.
AB - We provide an overview of groundbreaking studies that laid the foundation for our
current understanding of exercise-induced mitochondrial biogenesis and its
contribution to human skeletal muscle fitness. We highlight the mechanisms by
which skeletal muscle responds to the acute perturbations in cellular energy
homeostasis evoked by a single bout of endurance-based exercise and the
adaptations resulting from the repeated demands of exercise training that
ultimately promote mitochondrial biogenesis through hormetic feedback loops.
Despite intense research efforts to elucidate the cellular mechanisms
underpinning mitochondrial biogenesis in skeletal muscle, translating this basic
knowledge into improved metabolic health at the population level remains a future
challenge.
PMID- 28507196
TI - Health Benefits of Exercise.
AB - Overwhelming evidence exists that lifelong exercise is associated with a longer
health span, delaying the onset of 40 chronic conditions/diseases. What is
beginning to be learned is the molecular mechanisms by which exercise sustains
and improves quality of life. The current review begins with two short
considerations. The first short presentation concerns the effects of endurance
exercise training on cardiovascular fitness, and how it relates to improved
health outcomes. The second short section contemplates emerging molecular
connections from endurance training to mental health. Finally, approximately half
of the remaining review concentrates on the relationships between type 2
diabetes, mitochondria, and endurance training. It is now clear that physical
training is complex biology, invoking polygenic interactions within cells,
tissues/organs, systems, with remarkable cross talk occurring among the former
list.
PMID- 28507195
TI - Molecular Signaling Involved in Entry and Exit of Malaria Parasites from Host
Erythrocytes.
AB - During the blood stage, Plasmodium spp. merozoites invade host red blood cells
(RBCs), multiply, exit, and reinvade uninfected RBCs in a continuing cycle that
is responsible for all the clinical symptoms associated with malaria. Entry into
(invasion) and exit from (egress) RBCs are highly regulated processes that are
mediated by an array of parasite proteins with specific functional roles. Many of
these parasite proteins are stored in specialized apical secretory vesicles, and
their timely release is critical for successful invasion and egress. For example,
the discharge of parasite protein ligands to the apical surface of merozoites is
required for interaction with host receptors to mediate invasion, and the timely
discharge of proteases and pore-forming proteins helps in permeabilization and
dismantling of limiting membranes during egress. This review focuses on our
understanding of the signaling mechanisms that regulate apical organelle
secretion during host cell invasion and egress by malaria parasites. The review
also explores how understanding key signaling mechanisms in the parasite can open
opportunities to develop novel strategies to target Plasmodium parasites and
eliminate malaria.
PMID- 28507197
TI - Muscle-Adipose Tissue Cross Talk.
AB - Exercise training results in adaptations to both skeletal muscle and white
adipose tissue (WAT) and protects against metabolic disorders including obesity
and type 2 diabetes. Exercise-induced adaptations include an altered profile of
secreted proteins, both myokines (from skeletal muscle) and adipokines (from
adipose tissue). These secreted proteins may act in an endocrine manner to
facilitate tissue-to-tissue communication and "cross talk," likely working
together to improve overall metabolic health. Some studies suggest that
contracting skeletal muscles release myokines that may function to alter the
phenotype of WAT, including WAT "beiging," in which there is increased expression
of beige marker genes and increased presence of multilocular cells within the
WAT.
PMID- 28507198
TI - Modern Vector Control.
AB - The rapid spread of mosquito resistance to currently available insecticides, and
the current lack of an efficacious malaria vaccine are among many challenges that
affect large-scale efforts for malaria control. As goals of malaria elimination
and eradication are put forth, new vector-control paradigms and tools and/or
further optimization of current vector-control products are required to meet
public health demands. Vector control remains the most effective measure to
prevent malaria transmission and present gains against malaria mortality and
morbidity may be maintained as long as vector-intervention strategies are
sustained and adapted to underlying vector-related transmission dynamics. The
following provides a brief overview of vector-control strategies and tools either
in use or under development and evaluation that are intended to exploit key
entomological parameters toward driving down transmission.
PMID- 28507199
TI - Whole body vibration exercise combined with an extract of Coriandrum sativum
modify some biochemical/physiological parameters in rats.
AB - The aim of the present study was to evaluate the effect of the association of
whole body vibration (WBV) exercise with an aqueous extract of coriander on the
biodistribution of the radiopharmaceutical sodium pertechnetate, on the
concentration of some plasma biomarker, on the feed intake, on the body mass, and
on the stool consistency in rats. Rats were divided in four groups and submitted
to different treatments for 40 days. The control group (CON) received deionized
water. The group treated with coriander (COR) received the extract of coriander.
The rats that were exposed to WBV exercises (WBV-E) also received deionized
water. A group of animals received coriander and was exposed to WBV (COR + WBV
E). We found in testis a decrease (0.13 +/- 0.01 to 0.06 +/- 0.03) of the
percentages of injected radioactivity per gram (%ATI/g) in the WBV-E in
comparison with the COR. There is no significant alteration on the concentrations
of the plasma biomarkers. The feed intake showed a statistically significant
increase in WBV-E. No significant difference on the body mass was found. The
stool analysis showed a statistical difference on the consistency between COR
(hard and dry, darker) and all the other groups (normal). In conclusion, it was
verified that possible modifications in some biochemical/physiological parameters
of the rats submitted to WBV exercise would be capable to increase the feed
intake without changing the body mass, and normalizing the stool consistency
altered by the coriander supplementation. Further studies are needed to try to
understand better the biological effects involving the association of WBV
exercise and coriander.
PMID- 28507200
TI - Effects of microvirin monomers and oligomers on hepatitis C virus.
AB - Microvirin (MVN) is a carbohydrate-binding protein which shows high specificity
for high-mannose type N-glycan structures. In the present study, we tried to
identify whether MVN could bind to high-mannose containing hepatitis C virus
(HCV) envelope glycoproteins, which are heavily decorated high-mannose glycans.
In addition, recombinantly expressed MVN oligomers in di-, tri- and tetrameric
form were evaluated for their viral inhibition. MVN oligomers bound more
efficiently to HCV virions, and displayed in comparison with the MVN monomer a
higher neutralization potency against HCV infection. The antiviral effect was
furthermore affected by the peptide linker sequence connecting the MVN monomers.
The results indicate that MVN oligomers such as trimers and tetramers may be used
as future neutralization agents against HCV infections.
PMID- 28507201
TI - Sensitivity of non-small cell lung cancer to erlotinib is regulated by the
Notch/miR-223/FBXW7 pathway.
AB - Recent evidence supports a role for microRNA-223 (miR-223) in modulating tumor
cell sensitivity to chemotherapeutic drugs; however, its role in cellular
resistance to the effects of epidermal growth factor receptor tyrosine kinase
inhibitors (EGFR-TKIs) used in treatment of non-small cell lung cancer (NSCLC)
remains to be elucidated. The levels of miR-223 in parental cell line (HCC827)
and erlotinib resistant HCC827 cell line (HCC827/ER) were detected by qRT-PCR.
HCC827/ER cells were treated with MK-2206 to block the Akt signaling pathway or
RO4929097 to block the Notch signaling pathway, and then transfected with an miR
223 inhibitor or interference expression plasmid of F-Box/WD repeat-containing
protein 7 (FBXW7) or insulin-like growth factor 1 receptor (IGF1R). HCC827 cells
were transfected with miR-223 mimics. Next, CCK-8, colony formation, and flow
cytometric apoptosis assays were used to assess cell resistance to erlotinib.
When compared with its expression in HCC827 cells, miR-223 expression was
significantly up-regulated in HCC827/ER cells. Blocking either the Akt or Notch
signaling pathway and reducing miR-223 expression resulted in decreased
resistance in HCC827/ER cells. Conversely, increasing miR-223 expression induced
cell resistance to erlotinib in HCC827 cells. miR-223 enhanced resistance to
erlotinib by down-regulating FBXW7 expression. Reducing FBXW7 expression lowered
resistance to erlotinib in HCC827/ER cells, while interference with expression of
IGF1R produced no significant effect. This study demonstrated that NSCLC cells
can up-regulate their levels of miR-223 expression via the Akt and Notch
signaling pathways. miR-223 may serve as an important regulator of erlotinib
sensitivity in NSCLC cells by targeting FBXW7.
PMID- 28507202
TI - Determination of volatile organic compounds exhaled by cell lines derived from
hematological malignancies.
AB - : Background: The gas human exhaled contains many volatile organic compounds
(VOCs), which is related to the health status of body. Analysis of VOCs has been
proposed as a noninvasive diagnostic tool for certain cancers. Detailed research
on the VOCs in gas exhaled by cell can characterize cell type specific
metabolites and may be helpful to detect the cancer markers in clinical
practice.Methods: Solid-phase microextraction (SPME) gas chromatography-mass
spectrometry was used to detect VOCs in the headspace of tissue culture flask in
non-Hodgkin's lymphoma (NHL) cell line JEKO and acute mononuclear leukemia cell
line SHI-1, to elaborate the characteristic gaseous biomarkers of hematological
malignancies. While macrophage cells and lymphocytic cells were acted as control.
The blank group was only the RPMI 1640 medium containing 10% fetal calf serum
that without cells.Results: Comparing with control group, the concentration of
dimethyl sulfide, 2,4-dimethylheptane, methylbenzene, o-xylene, dodecane, and 1,3
di-tert-butylbenzene in JEKO cells was relatively higher, while the concentration
of ethanol, hexanal, and benzaldehyde was lower. In SHI-1 cells, the levels of
2,4-dimethylheptane, benzene, 4-methyldecane, chloroform, 3,7-dimethyl dodecane,
and hexadecane were significantly elevated, but the levels of hexanol and
cyclohexanol were distinctly reduced. CONCLUSIONS: This pilot study revealed that
the malignant hematological cells could change the components of VOCs in the cell
culture flask in a cell type-specific pattern. The traits of VOCs in our setting
offered new strategy for hematological malignancies tracing, and would act as
potential biomarkers in diagnosis of malignant hematological diseases.
PMID- 28507203
TI - Immunotherapy for Head and Neck Squamous Cell Carcinoma: A Review of Current and
Emerging Therapeutic Options.
AB - : Advances in the field of cancer immunotherapy have occurred rapidly over the
past decade. Exciting results from clinical trials have led to new treatment
options and improved survival for patients with a myriad of solid tumor
pathologies. However, questions remain unanswered regarding duration and timing
of therapy, combination regimens, appropriate biomarkers of disease, and optimal
monitoring of therapeutic response. This article reviews emerging
immunotherapeutic agents and significant clinical trials that have led to
advancements in the field of immuno-oncology for patients with head and neck
squamous cell carcinoma. IMPLICATIONS FOR PRACTICE: This review article
summarizes recently developed agents that harness the immune system to fight head
and neck squamous cell carcinoma. A brief review of the immune system and its
role in cancer development is included. Recently completed and emerging
therapeutic trials centering on the immune system and head and neck cancer are
reviewed.
PMID- 28507204
TI - Detection of an ALK Fusion in Colorectal Carcinoma by Hybrid Capture-Based Assay
of Circulating Tumor DNA.
AB - : ALK rearrangements have been observed in 0.05%-2.5% of patients with colorectal
cancers (CRCs) and are predicted to be oncogenic drivers largely mutually
exclusive of KRAS, NRAS, or BRAF alterations. Here we present the case of a
patient with metastatic CRC who was treatment naive at the time of molecular
testing. Initial ALK immunohistochemistry (IHC) staining was negative, but
parallel genomic profiling of both circulating tumor DNA (ctDNA) and tissue using
similar hybrid capture-based assays each identified an identical STRN-ALK fusion.
Subsequent ALK IHC staining of the same specimens was positive, suggesting that
the initial result was a false negative. This report is the first instance of an
ALK fusion in CRC detected using a ctDNA assay. KEY POINTS: Current guidelines
for colorectal cancer (CRC) only recommend genomic assessment of KRAS, NRAS,
BRAF, and microsatellite instability (MSI) status.ALK rearrangements are rare in
CRC, but patients with activating ALK fusions have responded to targeted
therapiesALK rearrangements can be detected by genomic profiling of ctDNA from
blood or tissue, and this methodology may be informative in cases where
immunohistochemistry (IHC) or other standard testing is negative.
PMID- 28507209
TI - In This Issue of Diabetes.
PMID- 28507207
TI - Role of osteocytes in mediating bone mineralization during hyperhomocysteinemia.
AB - Hyperhomocysteinemia (HHCY) is a risk factor for osteoporosis but whether HHCY
affects bone mineralization or not is still ambiguous. Herein we evaluated
whether homocysteine affects tissue mineral density (TMD) of cortical bone and if
so the role of osteocytes. CD1 mice administered with homocysteine (5 mg/100 g
body weight, i.p.) for 7, 15 and 30 days showed temporal changes in TMD and
osteocyte lacunar density in femoral cortices. Short-term administration of
homocysteine (day 7) increased osteocyte lacunar density and reduced TMD
evidenced by microCT50 while prolonged administration of homocysteine (day 30)
reinstated TMD and lacunar density to baseline values. Major differences were
decreased number of nucleated osteocyte lacunae, increased number of empty
lacunae and cleaved caspase 3-positive osteocyte lacunae in day 30 HHCY bone
evidenced by H&E staining and immunohistochemistry. Other differences were
induction in mineralization genes like Dmp1, Phex and Sost in cortical bone by
real-time PCR and increased number of Dmp1- and Sost-positive osteocyte lacunae
in day 30 HHCY bone evidenced by immunohistochemistry. Both HHCY day 7 and day 30
samples showed reduced Young's modulus demonstrating that biomechanical property
of bone was lost during early HHCY itself, which did not improve with recovery of
TMD. Our results thus demonstrate occurrence of two phases in cortical bone upon
HHCY: the early phase that involved loss of TMD and increase in osteocyte numbers
and a late phase that involved osteocyte reprogramming, apoptosis and
mineralization, which reinstated TMD but compromised biomechanical property. To
conclude, osteocytes have a potential role in arbitrating bone pathogenesis
during HHCY.
PMID- 28507205
TI - A Case of Metastatic Atypical Neuroendocrine Tumor with ALK Translocation and
Diffuse Brain Metastases.
AB - : A challenge in precision medicine requires identification of actionable driver
mutations. Critical to such effort is the deployment of sensitive and well
validated assays for mutation detection. Although identification of such
alterations within the tumor tissue remains the gold standard, many advanced non
small cell lung cancer cases have only limited tissue samples, derived from small
biopsies or fine-needle aspirates, available for testing. More recently,
noninvasive methods using either circulating tumor cells or tumor DNA (ctDNA)
have become an alternative method for identifying molecular biomarkers and
screening patients eligible for targeted therapies. In this article, we present a
case of a 52-year-old never-smoking male who presented with widely metastatic
atypical neuroendocrine tumor to the bones and the brain. Molecular genotyping
using DNA harvested from a bone metastasis was unsuccessful due to limited
material. Subsequent ctDNA analysis revealed an ALK translocation. The clinical
significance of the mutation in this particular cancer type and therapeutic
strategies are discussed. KEY POINTS: To our knowledge, this index case
represents the first reported ALK translocation identified in an atypical
carcinoid tumor.Liquid biopsy such as circulating tumor DNA is a feasible
alternative platform for identifying sensitizing genomic alterations.Second
generation ALK inhibitors represent a new paradigm for treating ALK-positive
patients with brain metastases.
PMID- 28507206
TI - Real-World Data on Prognostic Factors for Overall Survival in EGFR Mutation
Positive Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line
Gefitinib.
AB - BACKGROUND: This study aimed to identify independent prognostic factors for
overall survival (OS) of patients with advanced non-small cell lung cancer
(NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation
and receiving gefitinib as first-line treatment in real-world practice. MATERIALS
AND METHODS: We enrolled 226 patients from June 2011 to May 2013. During this
period, gefitinib was the only EGFR-tyrosine kinase inhibitor reimbursed by the
Bureau of National Health Insurance of Taiwan. RESULTS: The median progression
free survival and median OS were 11.9 months (95% confidence interval [CI]: 9.7
14.2) and 26.9 months (21.2-32.5), respectively. The Cox proportional hazards
regression model revealed that postoperative recurrence, performance status
(Eastern Cooperative Oncology Grade [ECOG] >=2), smoking index (>=20 pack-years),
liver metastasis at initial diagnosis, and chronic hepatitis C virus (HCV)
infection were independent prognostic factors for OS (hazard ratio [95% CI] 0.3
[0.11-0.83], p = .02; 2.69 [1.60-4.51], p < .001; 1.92 [1.24-2.97], p = .003;
2.26 [1.34-3.82], p = .002; 3.38 [1.85-7.78], p < .001, respectively). However,
brain metastasis (BM) at initial diagnosis or intracranial progression during
gefitinib treatment had no impact on OS (1.266 [0.83-1.93], p = .275 and 0.75
[0.48-1.19], p = .211, respectively). CONCLUSION: HCV infection, performance
status (ECOG >=2), newly diagnosed advanced NSCLC without prior operation, and
liver metastasis predicted poor OS in EGFR mutation-positive advanced NSCLC
patients treated with first-line gefitinib; however, neither BM at initial
diagnosis nor intracranial progression during gefitinib treatment had an impact
on OS. IMPLICATIONS FOR PRACTICE: The finding that chronic hepatitis C virus
(HCV) infection might predict poor overall survival (OS) in epidermal growth
factor receptor mutation-positive advanced non-small cell lung cancer (NSCLC)
patients treated with first-line gefitinib may raise awareness of benefit from
anti-HCV treatment in this patient population. Brain metastasis in the initial
diagnosis or intracranial progression during gefitinib treatment is not a
prognostic factor for OS. This study, which enrolled a real-world population of
NSCLC patients, including sicker patients who were not eligible for a clinical
trial, may have impact on guiding usual clinical practice.
PMID- 28507211
TI - Autologous Pluripotent Stem Cell-Derived beta-Like Cells for Diabetes Cellular
Therapy.
AB - Development of stem cell technologies for cell replacement therapy has progressed
rapidly in recent years. Diabetes has long been seen as one of the first
applications for stem cell-derived cells because of the loss of only a single
cell type-the insulin-producing beta-cell. Recent reports have detailed
strategies that overcome prior hurdles to generate functional beta-like cells
from human pluripotent stem cells in vitro, including from human induced
pluripotent stem cells (hiPSCs). Even with this accomplishment, addressing
immunological barriers to transplantation remains a major challenge for the
field. The development of clinically relevant hiPSC derivation methods from
patients and demonstration that these cells can be differentiated into beta-like
cells presents a new opportunity to treat diabetes without immunosuppression or
immunoprotective encapsulation or with only targeted protection from
autoimmunity. This review focuses on the current status in generating and
transplanting autologous beta-cells for diabetes cell therapy, highlighting the
unique advantages and challenges of this approach.
PMID- 28507210
TI - Diabetes, Pancreatogenic Diabetes, and Pancreatic Cancer.
AB - The relationships between diabetes and pancreatic ductal adenocarcinoma (PDAC)
are complex. Longstanding type 2 diabetes (T2DM) is a risk factor for pancreatic
cancer, but increasing epidemiological data point to PDAC as also a cause of
diabetes due to unknown mechanisms. New-onset diabetes is of particular interest
to the oncology community as the differentiation of new-onset diabetes caused by
PDAC as distinct from T2DM may allow for earlier diagnosis of PDAC. To address
these relationships and raise awareness of the relationships between PDAC and
diabetes, a symposium entitled Diabetes, Pancreatogenic Diabetes, and Pancreatic
Cancer was held at the American Diabetes Association's 76th Scientific Sessions
in June 2016. This article summarizes the data presented at that symposium,
describing the current understanding of the interrelationships between diabetes,
diabetes management, and pancreatic cancer, and identifies areas where additional
research is needed.
PMID- 28507212
TI - Adiponectin and beta-Cell Adaptation in Pregnancy.
PMID- 28507213
TI - Postprandial Suppression of Glucagon Secretion: A Puzzlement.
PMID- 28507215
TI - Comment on Adam et al. Metformin Effect on Nontargeted Metabolite Profiles in
Patients With Type 2 Diabetes and in Multiple Murine Tissues. Diabetes
2016;65:3776-3785.
PMID- 28507216
TI - Response to Comment on Adam et al. Metformin Effect on Nontargeted Metabolite
Profiles in Patients With Type 2 Diabetes and in Multiple Murine Tissues.
Diabetes 2016;65:3776-3785.
PMID- 28507217
TI - Comment on Ussar et al. Regulation of Glucose Uptake and Enteroendocrine Function
by the Intestinal Epithelial Insulin Receptor. Diabetes 2017;66:886-896.
PMID- 28507218
TI - Response to Comment on Ussar et al. Regulation of Glucose Uptake and
Enteroendocrine Function by the Intestinal Epithelial Insulin Receptor. Diabetes
2017;66:886-896.
PMID- 28507220
TI - Celebrating 35 Years of the AJNR: May 1982 edition.
PMID- 28507221
TI - Allocation of antiretroviral drugs to HIV-infected patients in Togo: perspectives
of people living with HIV and healthcare providers.
AB - AIM: To explore the way people living with HIV and healthcare providers in Togo
judge the priority of HIV-infected patients regarding the allocation of
antiretroviral drugs. METHOD: From June to September 2015, 200 adults living with
HIV and 121 healthcare providers living in Togo were recruited for the study.
They were presented with stories of a few lines depicting the situation of an HIV
infected patient and were instructed to judge the extent to which the patient
should be given priority for antiretroviral drugs. The stories were composed by
systematically varying the levels of four factors: (a) the severity of HIV
infection, (b) the financial situation of the patient, (c) the patient's family
responsibilities and (d) the time elapsed since the first consultation. RESULTS:
Five clusters were identified: 65% of the participants expressed the view that
patients who are poor and severely sick should be treated as a priority, 13%
prioritised treatment of patients who are poor and parents of small children, 12%
expressed the view that the poor should be treated as a priority, 4% preferred
that the sickest be treated as a priority and 6% wanted all patients to get
treatment. CONCLUSIONS: WHO's guideline regarding antiretroviral therapy
allocation (the sickest first as the sole criterion) currently in use in many
African countries does not reflect the preferences of Togolese people living with
HIV. For most HIV-infected patients in Togo, patients who cannot get treatment on
their own should be treated as a priority.
PMID- 28507219
TI - Subcutaneous golimumab for children with active polyarticular-course juvenile
idiopathic arthritis: results of a multicentre, double-blind, randomised
withdrawal trial.
AB - OBJECTIVE: This report aims to determine the safety, pharmacokinetics (PK) and
efficacy of subcutaneous golimumab in active polyarticular-course juvenile
idiopathic arthritis (polyJIA). METHODS: In this three-part randomised double
blinded placebo-controlled withdrawal trial, all patients received open-label
golimumab (30 mg/m2 of body surface area; maximum: 50 mg/dose) every 4 weeks
together with weekly methotrexate during Part 1 (weeks 0-16). Patients with at
least 30% improvement per American College of Rheumatology Criteria for JIA (JIA
ACR30) in Part 1 entered the double-blinded Part 2 (weeks 16-48) after 1:1
randomisation to continue golimumab or start placebo. In Part 3, golimumab was
continued or could be restarted as in Part 1. The primary outcome was JIA flares
in Part 2; secondary outcomes included JIA ACR50/70/90 responses, clinical
remission, PK and safety. RESULTS: Among 173 patients with polyJIA enrolled,
89.0% (154/173) had a JIA ACR30 response and 79.2%/65.9%/36.4% demonstrated JIA
ACR50/70/90 responses in Part 1. At week 48, the primary endpoint was not met as
treatment groups had comparable JIA flare rates (golimumab vs placebo: 32/78=41%
vs 36/76=47%; p=0.41), and rates of clinical remission were comparable (golimumab
vs placebo: 10/78=12.8% vs 9/76=11.8%). Adverse event and serious adverse event
rates were similar in the treatment groups during Part 2. Injection site
reactions occurred with <1% of all injections. PK analysis confirmed adequate
golimumab dosing for polyJIA. CONCLUSION: Although the primary endpoint was not
met, golimumab resulted in rapid, clinically meaningful, improvement in children
with active polyJIA. Golimumab was well tolerated, and no unexpected safety
events occurred. CLINICAL TRIAL REGISTRATION: NCT01230827; Results.
PMID- 28507222
TI - Meeting the goal of concurrent adolescent and adult licensure of HIV prevention
and treatment strategies.
AB - The ability of adolescents to access safe and effective new products for HIV
prevention and treatment is optimised by adolescent licensure at the same time
these products are approved and marketed for adults. Many adolescent product
development programmes for HIV prevention or treatment products may proceed
simultaneously with adult phase III development programmes. Appropriately
implemented, this strategy is not expected to delay licensure as information
regarding product efficacy can often be extrapolated from adults to adolescents,
and pharmacokinetic properties of drugs in adolescents are expected to be similar
to those in adults. Finally, adolescents enrolled in therapeutic HIV prevention
and treatment research can be considered adults, based on US Food and Drug
Administration (FDA) regulations and the appropriate application of state law.
The FDA permits local jurisdictions to apply state and local HIV/sexually
transmitted infection minor treatment laws so that adolescents who are HIV
positive or at risk of contracting HIV may be enrolled in therapeutic or
prevention trials without obtaining parental permission.
PMID- 28507223
TI - Should neurotechnological treatments offered to offenders always be in their best
interests?
AB - The paper critically discusses the moral view that neurotechnological behavioural
treatment for criminal offenders should only be offered if it is in their best
interests. First, I show that it is difficult to apply and assess the notion of
the offender's best interests unless one has a clear idea of what 'best
interests' means. Second, I argue that if one accepts that harmful punishment of
offenders has a place in the criminal justice system, it seems inconsistent not
to accept the practice of offering offenders treatment even when the state will
harm them in applying the treatment. Finally, leading penal theories like
consequentialists and retributivists would not accept that the offender's best
interests, at least in certain situations, impose a necessary condition for the
treatment of an offender.
PMID- 28507224
TI - c-MYC mRNA tail tale about glutamine control of transcription.
PMID- 28507226
TI - Peripheral retinopathy associated with Waldenstrom's macroglobulinaemia.
PMID- 28507227
TI - When two wrongs make a right: synchronized neuronal bursting from combined
electrical and inhibitory coupling.
AB - Synchronized cortical activities in the central nervous systems of mammals are
crucial for sensory perception, coordination and locomotory function. The
neuronal mechanisms that generate synchronous synaptic inputs in the neocortex
are far from being fully understood. In this paper, we study the emergence of
synchronization in networks of bursting neurons as a highly non-trivial, combined
effect of electrical and inhibitory connections. We report a counterintuitive
find that combined electrical and inhibitory coupling can synergistically induce
robust synchronization in a range of parameters where electrical coupling alone
promotes anti-phase spiking and inhibition induces anti-phase bursting. We reveal
the underlying mechanism, which uses a balance between hidden properties of
electrical and inhibitory coupling to act together to synchronize neuronal
bursting. We show that this balance is controlled by the duty cycle of the self
coupled system which governs the synchronized bursting rhythm.This article is
part of the themed issue 'Mathematical methods in medicine: neuroscience,
cardiology and pathology'.
PMID- 28507225
TI - Phosphorylation of Pkp1 by RIPK4 regulates epidermal differentiation and skin
tumorigenesis.
AB - Tissue homeostasis of skin is sustained by epidermal progenitor cells localized
within the basal layer of the skin epithelium. Post-translational modification of
the proteome, such as protein phosphorylation, plays a fundamental role in the
regulation of stemness and differentiation of somatic stem cells. However, it
remains unclear how phosphoproteomic changes occur and contribute to epidermal
differentiation. In this study, we survey the epidermal cell differentiation in a
systematic manner by combining quantitative phosphoproteomics with mammalian
kinome cDNA library screen. This approach identified a key signaling event,
phosphorylation of a desmosome component, PKP1 (plakophilin-1) by RIPK4 (receptor
interacting serine-threonine kinase 4) during epidermal differentiation. With
genome-editing and mouse genetics approach, we show that loss of function of
either Pkp1 or Ripk4 impairs skin differentiation and enhances epidermal
carcinogenesis in vivo Phosphorylation of PKP1's N-terminal domain by RIPK4 is
essential for their role in epidermal differentiation. Taken together, our study
presents a global view of phosphoproteomic changes that occur during epidermal
differentiation, and identifies RIPK-PKP1 signaling as novel axis involved in
skin stratification and tumorigenesis.
PMID- 28507228
TI - Understanding principles of integration and segregation using whole-brain
computational connectomics: implications for neuropsychiatric disorders.
AB - To survive in an ever-changing environment, the brain must seamlessly integrate a
rich stream of incoming information into coherent internal representations that
can then be used to efficiently plan for action. The brain must, however, balance
its ability to integrate information from various sources with a complementary
capacity to segregate information into modules which perform specialized
computations in local circuits. Importantly, evidence suggests that imbalances in
the brain's ability to bind together and/or segregate information over both space
and time is a common feature of several neuropsychiatric disorders. Most studies
have, however, until recently strictly attempted to characterize the principles
of integration and segregation in static (i.e. time-invariant) representations of
human brain networks, hence disregarding the complex spatio-temporal nature of
these processes. In the present Review, we describe how the emerging discipline
of whole-brain computational connectomics may be used to study the causal
mechanisms of the integration and segregation of information on behaviourally
relevant timescales. We emphasize how novel methods from network science and
whole-brain computational modelling can expand beyond traditional neuroimaging
paradigms and help to uncover the neurobiological determinants of the abnormal
integration and segregation of information in neuropsychiatric disorders.This
article is part of the themed issue 'Mathematical methods in medicine:
neuroscience, cardiology and pathology'.
PMID- 28507229
TI - Spread of competing viruses on heterogeneous networks.
AB - In this paper, we propose a model where two strains compete with each other at
the expense of common susceptible individuals on heterogeneous networks by using
pair-wise approximation closed by the probability-generating function (PGF). All
of the strains obey the susceptible-infected-recovered (SIR) mechanism. From a
special perspective, we first study the dynamical behaviour of an SIR model
closed by the PGF, and obtain the basic reproduction number via two methods. Then
we build a model to study the spreading dynamics of competing viruses and discuss
the conditions for the local stability of equilibria, which is different from the
condition obtained by using the heterogeneous mean-field approach. Finally, we
perform numerical simulations on Barabasi-Albert networks to complement our
theoretical research, and show some dynamical properties of the model with
competing viruses.This article is part of the themed issue 'Mathematical methods
in medicine: neuroscience, cardiology and pathology'.
PMID- 28507231
TI - Biological modelling of a computational spiking neural network with neuronal
avalanches.
AB - In recent years, an increasing number of studies have demonstrated that networks
in the brain can self-organize into a critical state where dynamics exhibit a
mixture of ordered and disordered patterns. This critical branching phenomenon is
termed neuronal avalanches. It has been hypothesized that the homeostatic level
balanced between stability and plasticity of this critical state may be the
optimal state for performing diverse neural computational tasks. However, the
critical region for high performance is narrow and sensitive for spiking neural
networks (SNNs). In this paper, we investigated the role of the critical state in
neural computations based on liquid-state machines, a biologically plausible
computational neural network model for real-time computing. The computational
performance of an SNN when operating at the critical state and, in particular,
with spike-timing-dependent plasticity for updating synaptic weights is
investigated. The network is found to show the best computational performance
when it is subjected to critical dynamic states. Moreover, the active-neuron
dominant structure refined from synaptic learning can remarkably enhance the
robustness of the critical state and further improve computational accuracy.
These results may have important implications in the modelling of spiking neural
networks with optimal computational performance.This article is part of the
themed issue 'Mathematical methods in medicine: neuroscience, cardiology and
pathology'.
PMID- 28507230
TI - Computational design of treatment strategies for proactive therapy on atopic
dermatitis using optimal control theory.
AB - Atopic dermatitis (AD) is a common chronic skin disease characterized by
recurrent skin inflammation and a weak skin barrier, and is known to be a
precursor to other allergic diseases such as asthma. AD affects up to 25% of
children worldwide and the incidence continues to rise. There is still
uncertainty about the optimal treatment strategy in terms of choice of treatment,
potency, duration and frequency. This study aims to develop a computational
method to design optimal treatment strategies for the clinically recommended
'proactive therapy' for AD. Proactive therapy aims to prevent recurrent flares
once the disease has been brought under initial control. Typically, this is done
by using an anti-inflammatory treatment such as a potent topical corticosteroid
intensively for a few weeks to 'get control', followed by intermittent weekly
treatment to suppress subclinical inflammation to 'keep control'. Using a hybrid
mathematical model of AD pathogenesis that we recently proposed, we
computationally derived the optimal treatment strategies for individual virtual
patient cohorts, by recursively solving optimal control problems using a
differential evolution algorithm. Our simulation results suggest that such an
approach can inform the design of optimal individualized treatment schedules that
include application of topical corticosteroids and emollients, based on the
disease status of patients observed on their weekly hospital visits. We
demonstrate the potential and the gaps of our approach to be applied to clinical
settings.This article is part of the themed issue 'Mathematical methods in
medicine: neuroscience, cardiology and pathology'.
PMID- 28507232
TI - Energy landscape analysis of neuroimaging data.
AB - Computational neuroscience models have been used for understanding neural
dynamics in the brain and how they may be altered when physiological or other
conditions change. We review and develop a data-driven approach to neuroimaging
data called the energy landscape analysis. The methods are rooted in statistical
physics theory, in particular the Ising model, also known as the (pairwise)
maximum entropy model and Boltzmann machine. The methods have been applied to
fitting electrophysiological data in neuroscience for a decade, but their use in
neuroimaging data is still in its infancy. We first review the methods and
discuss some algorithms and technical aspects. Then, we apply the methods to
functional magnetic resonance imaging data recorded from healthy individuals to
inspect the relationship between the accuracy of fitting, the size of the brain
system to be analysed and the data length.This article is part of the themed
issue 'Mathematical methods in medicine: neuroscience, cardiology and pathology'.
PMID- 28507234
TI - Modelling far field pacing for terminating spiral waves pinned to ischaemic
heterogeneities in cardiac tissue.
AB - In cardiac tissue, electrical spiral waves pinned to a heterogeneity can be
unpinned (and eventually terminated) using electric far field pulses and
recruiting the heterogeneity as a virtual electrode. While for isotropic media
the process of unpinning is much better understood, the case of an anisotropic
substrate with different conductivities in different directions still needs
intensive investigation. To study the impact of anisotropy on the unpinning
process, we present numerical simulations based on the bidomain formulation of
the phase I of the Luo and Rudy action potential model modified due to the
occurrence of acute myocardial ischaemia. Simulating a rotating spiral wave
pinned to an ischaemic heterogeneity, we compare the success of sequences of far
field pulses in the isotropic and the anisotropic case for spirals still in
transient or in steady rotation states. Our results clearly indicate that the
range of pacing parameters resulting in successful termination of pinned spiral
waves is larger in anisotropic tissue than in an isotropic medium.This article is
part of the themed issue 'Mathematical methods in medicine: neuroscience,
cardiology and pathology'.
PMID- 28507233
TI - Transient sequences in a hypernetwork generated by an adaptive network of spiking
neurons.
AB - We propose a model of an adaptive network of spiking neurons that gives rise to a
hypernetwork of its dynamic states at the upper level of description. Left to
itself, the network exhibits a sequence of transient clustering which relates to
a traffic in the hypernetwork in the form of a random walk. Receiving inputs the
system is able to generate reproducible sequences corresponding to stimulus
specific paths in the hypernetwork. We illustrate these basic notions by a simple
network of discrete-time spiking neurons together with its FPGA realization and
analyse their properties.This article is part of the themed issue 'Mathematical
methods in medicine: neuroscience, cardiology and pathology'.
PMID- 28507235
TI - Assessing the strength of cardiac and sympathetic baroreflex controls via
transfer entropy during orthostatic challenge.
AB - The study assesses the strength of the causal relation along baroreflex (BR) in
humans during an incremental postural challenge soliciting the BR. Both cardiac
BR (cBR) and sympathetic BR (sBR) were characterized via BR sequence approaches
from spontaneous fluctuations of heart period (HP), systolic arterial pressure
(SAP), diastolic arterial pressure (DAP) and muscle sympathetic nerve activity
(MSNA). A model-based transfer entropy method was applied to quantify the
strength of the coupling from SAP to HP and from DAP to MSNA. The confounding
influences of respiration were accounted for. Twelve young healthy subjects (20
36 years, nine females) were sequentially tilted at 0 degrees , 20 degrees , 30
degrees and 40 degrees . We found that (i) the strength of the causal relation
along the cBR increases with tilt table inclination, while that along the sBR is
unrelated to it; (ii) the strength of the causal coupling is unrelated to the
gain of the relation; (iii) transfer entropy indexes are significantly and
positively associated with simplified causality indexes derived from BR sequence
analysis. The study proves that causality indexes are complementary to
traditional characterization of the BR and suggests that simple markers derived
from BR sequence analysis might be fruitfully exploited to estimate causality
along the BR.This article is part of the themed issue 'Mathematical methods in
medicine: neuroscience, cardiology and pathology'.
PMID- 28507236
TI - Dynamics of the cell-mediated immune response to tumour growth.
AB - Using a hybrid cellular automaton, we investigate the transient and asymptotic
dynamics of the cell-mediated immune response to tumour growth. We analyse the
correspondence between this dynamics and the three phases of the theory of
immunoedition: elimination, equilibrium and escape. Our results demonstrate that
the immune system can keep a tumour dormant for long periods of time, but that
this dormancy is based on a frail equilibrium between the mechanisms that spur
the immune response and the growth of the tumour. Thus, we question the capacity
of the cell-mediated immune response to sustain long periods of dormancy, as
those appearing in recurrent disease. We suggest that its role might be rather to
synergize with other types of tumour dormancy.This article is part of the themed
issue 'Mathematical methods in medicine: neuroscience, cardiology and pathology'.
PMID- 28507237
TI - Multiscale ordinal network analysis of human cardiac dynamics.
AB - In this study, we propose a new information theoretic measure to quantify the
complexity of biological systems based on time-series data. We demonstrate the
potential of our method using two distinct applications to human cardiac
dynamics. Firstly, we show that the method clearly discriminates between segments
of electrocardiogram records characterized by normal sinus rhythm, ventricular
tachycardia and ventricular fibrillation. Secondly, we investigate the multiscale
complexity of cardiac dynamics with respect to age in healthy individuals using
interbeat interval time series and compare our findings with a previous study
which established a link between age and fractal-like long-range correlations.
The method we use is an extension of the symbolic mapping procedure originally
proposed for permutation entropy. We build a Markov chain of the dynamics based
on order patterns in the time series which we call an ordinal network, and from
this model compute an intuitive entropic measure of transitional complexity. A
discussion of the model parameter space in terms of traditional time delay
embedding provides a theoretical basis for our multiscale approach. As an
ancillary discussion, we address the practical issue of node aliasing and how
this effects ordinal network models of continuous systems from discrete time
sampled data, such as interbeat interval time series.This article is part of the
themed issue 'Mathematical methods in medicine: neuroscience, cardiology and
pathology'.
PMID- 28507238
TI - Clustering: how much bias do we need?
AB - Scientific investigations in medicine and beyond increasingly require
observations to be described by more features than can be simultaneously
visualized. Simply reducing the dimensionality by projections destroys essential
relationships in the data. Similarly, traditional clustering algorithms introduce
data bias that prevents detection of natural structures expected from generic
nonlinear processes. We examine how these problems can best be addressed, where
in particular we focus on two recent clustering approaches, Phenograph and
Hebbian learning clustering, applied to synthetic and natural data examples. Our
results reveal that already for very basic questions, minimizing clustering bias
is essential, but that results can benefit further from biased post
processing.This article is part of the themed issue 'Mathematical methods in
medicine: neuroscience, cardiology and pathology'.
PMID- 28507239
TI - Pulsatile flow in ventricular catheters for hydrocephalus.
AB - The obstruction of ventricular catheters (VCs) is a major problem in the standard
treatment of hydrocephalus, the flow pattern of the cerebrospinal fluid (CSF)
being one important factor thereof. As a first approach to this problem, some of
the authors studied previously the CSF flow through VCs under time-independent
boundary conditions by means of computational fluid dynamics in three-dimensional
models. This allowed us to derive a few basic principles which led to designs
with improved flow patterns regarding the obstruction problem. However, the flow
of the CSF has actually a pulsatile nature because of the heart beating and blood
flow. To address this fact, here we extend our previous computational study to
models with oscillatory boundary conditions. The new results will be compared
with the results for constant flows and discussed. It turns out that the
corrections due to the pulsatility of the CSF are quantitatively small, which
reinforces our previous findings and conclusions.This article is part of the
themed issue 'Mathematical methods in medicine: neuroscience, cardiology and
pathology'.
PMID- 28507240
TI - Mathematical methods in medicine: neuroscience, cardiology and pathology.
AB - The application of mathematics, natural sciences and engineering to medicine is
gaining momentum as the mutual benefits of this collaboration become increasingly
obvious. This theme issue is intended to highlight the trend in the case of
mathematics. Specifically, the scope of this theme issue is to give a general
view of the current research in the application of mathematical methods to
medicine, as well as to show how mathematics can help in such important aspects
as understanding, prediction, treatment and data processing. To this end, three
representative specialties have been selected: neuroscience, cardiology and
pathology. Concerning the topics, the 12 research papers and one review included
in this issue cover biofluids, cardiac and virus dynamics, computational
neuroscience, functional magnetic resonance imaging data processing, neural
networks, optimization of treatment strategies, time-series analysis and tumour
growth. In conclusion, this theme issue contains a collection of fine
contributions at the intersection of mathematics and medicine, not as an exercise
in applied mathematics but as a multidisciplinary research effort that interests
both communities and our society in general.This article is part of the themed
issue 'Mathematical methods in medicine: neuroscience, cardiology and pathology'.
PMID- 28507242
TI - An RpoHI-Dependent Response Promotes Outgrowth after Extended Stationary Phase in
the Alphaproteobacterium Rhodobacter sphaeroides.
AB - Under unfavorable growth conditions, bacteria enter stationary phase and can
maintain cell viability over prolonged periods with no increase in cell number.
To obtain insights into the regulatory mechanisms that allow bacteria to resume
growth when conditions become favorable again (outgrowth), we performed global
transcriptome analyses at different stages of growth for the alphaproteobacterium
Rhodobacter sphaeroides The majority of genes were not differentially expressed
across growth phases. After a short stationary phase (about 20 h after growth
starts to slow down), only 7% of the genes showed altered expression (fold change
of >1.6 or less than -1.6, corresponding to a log2 fold change of >0.65 or less
than -0.65, respectively) compared to expression at exponential phase. Outgrowth
induced a distinct response in gene expression which was strongly influenced by
the length of the preceding stationary phase. After a long stationary phase
(about 64 h after growth starts to slow down), a much larger number of genes
(15.1%) was induced in outgrowth than after a short stationary phase (1.7%). Many
of those genes are known members of the RpoHI/RpoHII regulons and have
established functions in stress responses. A main effect of RpoHI on the
transcriptome in outgrowth after a long stationary phase was confirmed. Growth
experiments with mutant strains further support an important function in
outgrowth after prolonged stationary phase for the RpoHI and RpoHII sigma
factors.IMPORTANCE In natural environments, the growth of bacteria is limited
mostly by lack of nutrients or other unfavorable conditions. It is important for
bacterial populations to efficiently resume growth after being in stationary
phase, which may last for long periods. Most previous studies on growth-phase
dependent gene expression did not address outgrowth after stationary phase. This
study on growth-phase-dependent gene regulation in a model alphaproteobacterium
reveals, for the first time, that the length of the stationary phase strongly
impacts the transcriptome during outgrowth. The alternative sigma factors RpoHI
and RpoHII, which are important regulators of stress responses in
alphaproteobacteria, play a major role during outgrowth following prolonged
stationary phase. These findings provide the first insight into the regulatory
mechanisms enabling efficient outgrowth.
PMID- 28507241
TI - An Amino Acid Substitution in RNA Polymerase That Inhibits the Utilization of an
Alternative Sigma Factor.
AB - Sigma (sigma) factors direct gene transcription by binding to and determining the
promoter recognition specificity of RNA polymerase (RNAP) in bacteria. Genes
transcribed under the control of alternative sigma factors allow cells to respond
to stress and undergo developmental processes, such as sporulation in Bacillus
subtilis, in which gene expression is controlled by a cascade of alternative
sigma factors. Binding of sigma factors to RNA polymerase depends on the coiled
coil (or clamp helices) motif of the beta' subunit. We have identified an amino
acid substitution (L257P) in the coiled coil that markedly inhibits the function
of sigmaH, the earliest-acting alternative sigma factor in the sporulation
cascade. Cells with this mutant RNAP exhibited an early and severe block in
sporulation but not in growth. The mutant was strongly impaired in sigmaH
directed gene expression but not in the activity of the stress-response sigma
factor sigmaB Pulldown experiments showed that the mutant RNAP was defective in
associating with sigmaH but could still associate with sigmaA and sigmaB The
differential effects of the L257P substitution on sigma factor binding to RNAP
are likely due to a conformational change in the beta' coiled coil that is
specifically detrimental for interaction with sigmaH This is the first example,
to our knowledge, of an amino acid substitution in RNAP that exhibits a strong
differential effect on a particular alternative sigma factor.IMPORTANCE In
bacteria, all transcription is mediated by a single multisubunit RNA polymerase
(RNAP) enzyme. However, promoter-specific transcription initiation necessitates
that RNAP associates with a sigma factor. Bacteria contain a primary sigma factor
that directs transcription of housekeeping genes and alternative sigma factors
that direct transcription in response to environmental or developmental cues. We
identified an amino acid substitution (L257P) in the B. subtilis beta' subunit
whereby RNAPL257P associates with some sigma factors (sigmaA and sigmaB) and
enables vegetative cell growth but is defective in utilization of sigmaH and is
consequently blocked for sporulation. To our knowledge, this is the first
identification of an amino acid substitution within the core enzyme that affects
utilization of a specific sigma factor.
PMID- 28507243
TI - Modular Organization of the NusA- and NusG-Stimulated RNA Polymerase Pause Signal
That Participates in the Bacillus subtilis trp Operon Attenuation Mechanism.
AB - The Bacillus subtilis trpEDCFBA operon is regulated by a transcription
attenuation mechanism in which tryptophan-activated TRAP binds to the nascent
transcript and blocks the formation of an antiterminator structure such that the
formation of an overlapping intrinsic terminator causes termination in the 5'
untranslated region (5' UTR). In the absence of bound TRAP, the antiterminator
forms and transcription continues into the trp genes. RNA polymerase pauses at
positions U107 and U144 in the 5' UTR. The general transcription elongation
factors NusA and NusG stimulate pausing at both positions. NusG-stimulated
pausing at U144 requires sequence-specific contacts with a T tract in the
nontemplate DNA (ntDNA) strand within the paused transcription bubble. Pausing at
U144 participates in a trpE translation repression mechanism. Since U107 just
precedes the critical overlap between the antiterminator and terminator
structures, pausing at this position is thought to participate in attenuation.
Here we carried out in vitro pausing and termination experiments to identify
components of the U107 pause signal and to determine whether pausing affects the
termination efficiency in the 5' UTR. We determined that the U107 and U144 pause
signals are organized in a modular fashion containing distinct RNA hairpin, U
tract, and T-tract components. NusA-stimulated pausing was affected by hairpin
strength and the U-tract sequence, whereas NusG-stimulated pausing was affected
by hairpin strength and the T-tract sequence. We also determined that pausing at
U107 results in increased TRAP-dependent termination in the 5' UTR, implying that
NusA- and NusG-stimulated pausing participates in the trp operon attenuation
mechanism by providing additional time for TRAP binding.IMPORTANCE The expression
of several bacterial operons is controlled by regulated termination in the 5'
untranslated region (5' UTR). Transcription attenuation is defined as situations
in which the binding of a regulatory molecule promotes transcription termination
in the 5' UTR, with the default being transcription readthrough into the
downstream genes. RNA polymerase pausing is thought to participate in several
attenuation mechanisms by synchronizing the position of RNA polymerase with RNA
folding and/or regulatory factor binding, although this has only been shown in a
few instances. We found that NusA- and NusG-stimulated pausing participates in
the attenuation mechanism controlling the expression of the Bacillus subtilis trp
operon by increasing the TRAP-dependent termination efficiency. The pause signal
is organized in a modular fashion containing RNA hairpin, U-tract, and T-tract
components.
PMID- 28507247
TI - The Long and Winding Road After FDA Approval: A Medical Device Industry
Perspective.
PMID- 28507244
TI - Inhibition of Staphylococcus aureus Cell Wall Biosynthesis by Desleucyl
Oritavancin: a Quantitative Peptidoglycan Composition Analysis by Mass
Spectrometry.
AB - Oritavancin is a lipoglycopeptide antibiotic that exhibits potent activities
against vancomycin-resistant Gram-positive pathogens. Oritavancin differs from
vancomycin by a hydrophobic side chain attached to the drug disaccharide, which
forms a secondary binding site to enable oritavancin binding to the cross-linked
peptidoglycan in the cell wall. The mode of action of secondary binding site was
investigated by measuring the changes in the peptidoglycan composition of
Staphylococcus aureus grown in the presence of desleucyl-oritavancin at
subinhibitory concentration using liquid chromatography-mass spectrometry (LC
MS). Desleucyl-oritavancin is an Edman degradation product of oritavancin that
exhibits potent antibacterial activities despite the damaged d-Ala-d-Ala binding
site due to its functional secondary binding site. Accurate quantitative
peptidoglycan composition analysis based on 83 muropeptide ions determined that
cell walls of S. aureus grown in the presence of desleucyl-oritavancin showed a
reduction of peptidoglycan cross-linking, increased muropeptides with a
tetrapeptide-stem structure, decreased O-acetylation of MurNAc, and increased N
deacetylation of GlcNAc. The changes in peptidoglycan composition suggest that
desleucyl-oritavancin targets the peptidoglycan template to induce cell wall
disorder and interferes with cell wall maturation.IMPORTANCE Oritavancin is a
lipoglycopeptide antibiotic with a secondary binding site that targets the cross
linked peptidoglycan bridge structure in the cell wall. Even after the loss of
its primary d-Ala-d-Ala binding site through Edman degradation, desleucyl
oritavancin exhibits potent antimicrobial activities through its still
functioning secondary binding site. In this study, we characterized the mode of
action for desleucyl-oritavancin's secondary binding site using LC-MS.
Peptidoglycan composition analysis of desleucyl-oritavancin-treated S. aureus was
performed by determining the relative abundances of 83 muropeptide ions matched
from a precalculated library through integrating extracted ion chromatograms. Our
work highlights the use of quantitative peptidoglycan composition analysis by LC
MS to provide insights into the mode of action of glycopeptide antibiotics.
PMID- 28507245
TI - Conformational Changes of an Interdomain Linker Mediate Mechanical Signal
Transmission in Sensor Kinase BvgS.
AB - The whooping cough agent, Bordetella pertussis, controls the expression of its
large virulence regulon in a coordinated manner through the two-component system
BvgAS. BvgS is a dimeric, multidomain sensor kinase. Each monomer comprises, in
succession, tandem periplasmic Venus flytrap (VFT) domains, a transmembrane
segment, a cytoplasmic Per-Arnt-Sim (PAS) domain, a kinase module, and additional
phosphorelay domains. BvgS shifts between kinase and phosphatase modes of
activity in response to chemical modulators that modify the clamshell motions of
the VFT domains. We have shown previously that this regulation involves a shift
between distinct states of conformation and dynamics of the two-helix coiled-coil
linker preceding the enzymatic module. In this work, we determined the mechanism
of signal transduction across the membrane via a first linker, which connects the
VFT and PAS domains of BvgS, using extensive cysteine cross-linking analyses and
other approaches. Modulator perception by the periplasmic domains appears to
trigger a small, symmetrical motion of the transmembrane segments toward the
periplasm, causing rearrangements of the noncanonical cytoplasmic coiled coil
that follows. As a consequence, the interface of the PAS domains is modified,
which affects the second linker and eventually causes the shift of enzymatic
activity. The major features of this first linker are well conserved among BvgS
homologs, indicating that the mechanism of signal transduction unveiled here is
likely to be generally relevant for this family of sensor
kinases.IMPORTANCEBordetella pertussis produces virulence factors coordinately
regulated by the two-component system BvgAS. BvgS is a sensor kinase, and BvgA is
a response regulator that activates gene transcription when phosphorylated by
BvgS. Sensor kinases homologous to BvgS are also found in other pathogens. Our
goal is to decipher the mechanisms of BvgS signaling, since these sensor kinases
may represent new targets for antibacterial agents. Signal perception by the
sensor domains of BvgS triggers small motions of the helical linker region
underneath. The protein domain that follows this linker undergoes a large
conformational change that amplifies the initial signal, causing a shift of
activity from kinase to phosphatase. Because BvgS homologs harbor similar
regions, these signaling mechanisms are likely to apply generally to that family
of sensor kinases.
PMID- 28507248
TI - New Hope For People With Dysglycemia and Cardiovascular Disease Manifestations:
Reduction of Acute Coronary Events With Pioglitazone.
PMID- 28507249
TI - Response to Outlier Status: Lessons From Public Reporting for Percutaneous
Coronary Intervention.
PMID- 28507246
TI - The Pneumococcal Type 1 Pilus Genes Are Thermoregulated and Are Repressed by a
Member of the Snf2 Protein Family.
AB - In Streptococcus pneumoniae, the type 1 pilus is involved in many steps of
pathogenesis, including adherence to epithelial cells, mediation of inflammation,
escape from macrophages, and the formation of biofilms. The type 1 pilus genes
are expressed in a bistable fashion with cells switching between "on" and "off"
expression states. Bistable expression of these genes is due to their control by
RlrA, a positive regulator subject to control by a positive-feedback loop. The
type 1 pilus genes are also thought to be negatively regulated by a large number
of repressors. Here we show that expression of the type 1 pilus genes is
thermosensitive and switched off at growth temperatures below 31 degrees C. We
also report that the on expression state of the type 1 pilus genes is highly
stable, a phenomenon which we show likely contributed to the erroneous
identification of many proteins as negative regulators of these genes. Finally,
we exploited the effect of low temperature on pilus gene expression to help
identify SP_1523, an Snf2-type protein, as a novel negative regulator of the
pilus genes. Our findings establish that the type 1 pilus genes are
thermoregulated and are repressed by a member of the Snf2 protein family. They
also refute the notion that these genes are controlled by 8 previously described
negative regulators.IMPORTANCEStreptococcus pneumoniae is the leading cause of
death from respiratory infections in children. Many bacterial factors contribute
to pneumococcal virulence and nasopharyngeal colonization. The type 1
pneumococcal pilus plays an important role in mouse models and in epithelial
adherence and is expressed in a bistable fashion. Here we show that the "on"
state is highly stable, which may explain the prior misidentification of negative
regulators of pilus expression. We also show that expression of pilus genes is
thermosensitive: virtually no expression can be detected at temperatures found in
the anterior nares of humans. We took advantage of this property to identify a
negative regulator of pilus expression, a member of a family of proteins widely
conserved across Gram-positive bacteria.
PMID- 28507250
TI - A Rock and a Hard Place: Chiseling Away at the Multiple Mechanisms of Aortic
Stenosis.
PMID- 28507251
TI - Stress Testing in Asymptomatic Aortic Stenosis.
AB - Aortic stenosis is 1 of the most common heart valve diseases among adults. When
symptoms develop, prognosis is poor, and current guidelines recommend prompt
aortic valve replacement. Depending of the severity of the aortic stenosis and
the presence of concomitant heart disease and medical comorbidities, stress
testing represents a reasonable strategy to help better risk stratify
asymptomatic patients. The present report provides a comprehensive review of the
current available data on stress testing in aortic stenosis and subsequently
summarizes its potential for guiding the optimal timing of aortic valve
replacement.
PMID- 28507252
TI - Winter Is Coming After a Cardiac Arrest.
PMID- 28507253
TI - Primary Stable Microvascular Angina: A Long-Term Clinical Follow-Up Study.
PMID- 28507254
TI - Letter by Ma et al Regarding Article, "Neuroprotective Effects of the Glucagon
Like Peptide-1 Analog Exenatide After Out-of-Hospital Cardiac Arrest: A
Randomized Controlled Trial".
PMID- 28507255
TI - Response by Wiberg et al to Letter Regarding Article, "Neuroprotective Effects of
the Glucagon-Like Peptide-1 Analog Exenatide After Out-of-Hospital Cardiac
Arrest: A Randomized Controlled Trial".
PMID- 28507256
TI - Letter by Tuncez et al Regarding Article, "Identifying Patients at Risk for
Prehospital Sudden Cardiac Arrest at the Early Phase of Myocardial Infarction:
The e-MUST Study (Evaluation en Medecine d'Urgence des Strategies Therapeutiques
des infarctus du myocarde)".
PMID- 28507258
TI - Letter by Rottenberg Regarding Article, "Conventional Versus Compression-Only
Versus No Bystander Cardiopulmonary Resuscitation for Pediatric Out-of-Hospital
Cardiac Arrest".
PMID- 28507257
TI - Response by Karam et al to Letter Regarding Article, "Identifying Patients at
Risk for Prehospital Sudden Cardiac Arrest at the Early Phase of Myocardial
Infarction: The e-MUST Study (Evaluation en Medecine d'Urgence des Strategies
Therapeutiques des infarctus du myocarde)".
PMID- 28507259
TI - Spotlight on the May 16 issue.
PMID- 28507262
TI - Editors' Note.
PMID- 28507260
TI - Reprogramming cells from Gulf War veterans into neurons to study Gulf War
illness.
AB - Gulf War illness (GWI), which afflicts at least 25% of veterans who served in the
1990-1991 war in the Persian Gulf, is thought to be caused by deployment
exposures to various neurotoxicants, including pesticides, anti-nerve gas pills,
and low-level nerve agents including sarin/cyclosarin. GWI is a multisymptom
disorder characterized by fatigue, joint pain, cognitive problems, and
gastrointestinal complaints. The most prominent symptoms of GWI (memory problems,
poor attention/concentration, chronic headaches, mood alterations, and impaired
sleep) suggest that the disease primarily affects the CNS. Development of
urgently needed treatments depends on experimental models appropriate for testing
mechanistic hypotheses and for screening therapeutic compounds. Rodent models
have been useful thus far, but are limited by their inability to assess the
contribution of genetic or epigenetic background to the disease, and because
disease-vulnerable proteins and pathways may be different in humans relative to
rodents. As of yet, no postmortem tissue from the veterans has become available
for research. We are moving forward with a paradigm shift in the study of GWI,
which utilizes contemporary stem cell technology to convert somatic cells from
Gulf War veterans into pluripotent cell lines that can be differentiated into
various cell types, including neurons, glia, muscle, or other relevant cell
types. Such cell lines are immortal and will be a resource for GWI researchers to
pursue mechanistic hypotheses and therapeutics.
PMID- 28507261
TI - Pure sensory ganglionopathy as the first sign of relapse in non-Hodgkin lymphoma.
PMID- 28507264
TI - Author response: Mystery Case: CSF-1R mutation is a cause of intracranial
cerebral calcifications, cysts, and leukoencephalopathy.
PMID- 28507263
TI - Letter re: Mystery Case: CSF-1R mutation is a cause of intracranial cerebral
calcifications, cysts, and leukoencephalopathy.
PMID- 28507266
TI - Mystery Case: CSF-1R mutation is a cause of intracranial cerebral calcifications,
cysts, and leukoencephalopathy.
PMID- 28507265
TI - Summary author response: Mystery Case: CSF-1R mutation is a cause of intracranial
cerebral calcifications, cysts, and leukoencephalopathy.
PMID- 28507267
TI - Teaching NeuroImages: Takayasu arteritis: Neuroimaging progression after
immunosuppressant treatment.
PMID- 28507268
TI - Teaching NeuroImages: Prominent spinal cord atrophy and white matter changes in
adult polyglucosan body disease.
PMID- 28507271
TI - Correction: Integration of Novel Agents into the Care of Patients with Multiple
Myeloma.
PMID- 28507269
TI - Randomized, Multicenter Trial of ARTSS-2 (Argatroban With Recombinant Tissue
Plasminogen Activator for Acute Stroke).
AB - BACKGROUND AND PURPOSE: We conducted a randomized exploratory study to assess
safety and the probability of a favorable outcome with adjunctive argatroban, a
direct thrombin-inhibitor, administered to recombinant tissue-type plasminogen
activator (r-tPA)-treated ischemic stroke patients. METHODS: Patients treated
with standard-dose r-tPA, not receiving endovascular therapy, were randomized to
receive no argatroban or argatroban (100 MUg/kg bolus) followed by infusion of
either 1 (low dose) or 3 MUg/kg per minute (high dose) for 48 hours. Safety was
incidence of symptomatic intracerebral hemorrhage. Probability of clinical
benefit (modified Rankin Scale score 0-1 at 90 days) was estimated using a
conservative Bayesian Poisson model (neutral prior probability centered at
relative risk, 1.0 and 95% prior intervals, 0.33-3.0). RESULTS: Ninety patients
were randomized: 29 to r-tPA alone, 30 to r-tPA+low-dose argatroban, and 31 to r
tPA+high-dose argatroban. Rates of symptomatic intracerebral hemorrhage were
similar among control, low-dose, and high-dose arms: 3/29 (10%), 4/30 (13%), and
2/31 (7%), respectively. At 90 days, 6 (21%) r-tPA alone, 9 (30%) low-dose, and
10 (32%) high-dose patients were with modified Rankin Scale score 0 to 1. The
relative risks (95% credible interval) for modified Rankin Scale score 0 to 1
with low, high, and either low or high dose argatroban were 1.17 (0.57-2.37),
1.27 (0.63-2.53), and 1.34 (0.68-2.76), respectively. The probability that
adjunctive argatroban was superior to r-tPA alone was 67%, 74%, and 79% for low,
high, and low or high dose, respectively. CONCLUSIONS: In patients treated with r
tPA, adjunctive argatroban was not associated with increased risk of symptomatic
intracerebral hemorrhage and provides evidence that a definitive effectiveness
trial is indicated. CLINICAL TRIAL REGISTRATION: URL:
http://www.clinicaltrials.gov. Unique Identifier: NCT01464788.
PMID- 28507274
TI - Targeted next generation sequencing identifies somatic mutations and gene fusions
in papillary thyroid carcinoma.
AB - 138 papillary thyroid carcinoma (PTC) samples were assessed for somatic mutation
profile and fusion genes by targeted resequencing using a cancer panel
(ThyGenCapTM) targeting 244 cancer-related genes and 20 potential fusion genes.
At least one genetic alteration (including mutations and fusion genes) was
observed in 118/138 (85.5%) samples. The most frequently mutated gene was BRAF
V600E (57.2%). Moreover, we identified 11 fusion genes including eight previously
reported ones and three novel fusion genes, UEVLD-RET, OSBPL9-BRAF, and SQSTM1
NTRK3. Alterations affecting the mitogen-activated protein kinase (MAPK)
signaling pathway components were seen in 69.6% of the PTC cases and all of these
driver mutations were mutually exclusive. Univariate analysis ascertained that
the fusion genes were strongly associated with distinct clinicopathological
characteristics, such as young age, local invasion, extensive metastasis, and
disease stage. In conclusion, our approach facilitated simultaneous high
throughput detection of gene fusions and somatic mutations in PTC samples.
PMID- 28507272
TI - Phosphatidylinositol 5-phosphate 4-kinase regulates early endosomal dynamics
during clathrin-mediated endocytosis.
AB - Endocytic turnover is essential for the regulation of the protein composition and
function of the plasma membrane, and thus affects the plasma membrane levels of
many receptors. In Drosophila melanogaster photoreceptors, photon absorption by
the G-protein-coupled receptor (GPCR) rhodopsin 1 (Rh1; also known as NinaE)
triggers its endocytosis through clathrin-mediated endocytosis (CME). We find
that CME of Rh1 is regulated by phosphatidylinositol 5 phosphate 4-kinase
(PIP4K). Flies lacking PIP4K show mislocalization of Rh1 on expanded
endomembranes within the cell body. This mislocalization of Rh1 was dependent on
the formation of an expanded Rab5-positive compartment. The Rh1-trafficking
defect in PIP4K-depleted cells could be suppressed by downregulating Rab5
function or by selectively reconstituting PIP4K in the PI3P-enriched early
endosomal compartment of photoreceptors. We also found that loss of PIP4K was
associated with increased CME and an enlarged Rab5-positive compartment in
cultured Drosophila cells. Collectively, our findings define PIP4K as a novel
regulator of early endosomal homeostasis during CME.
PMID- 28507275
TI - Quantitative proteomics profiling reveals activation of mTOR pathway in
trastuzumab resistance.
AB - Trastuzumab is an antibody-based therapy drug targeting HER2-overexpressing
tumors. While it has been proven to be very successful initially, most patients
eventually develop resistance to trastuzumab. The mechanism of drug resistance is
not well understood. Identifying pathways that mediate trastuzumab resistance
will improve our understanding of the underlying mechanism and is crucial for the
development of therapeutic strategies to overcome resistance.Here we report a
quantitative proteomics profiling of a trastuzumab-sensitive (T-S) gastric cancer
cell line NCI N87 and a trastuzumab-resistant NCI N87 (T-R) subline generated by
low-dose, continuous trastuzumab treatment. By identifying proteins
differentially expressed in these two cell lines, we show that multiple pathways
including mTOR, Wnt, DNA damage response and metabolic pathways are significantly
altered. We further confirm by western blotting that protein levels of multiple
components of the mTOR pathway, including mTOR, AKT and RPS6KB1, are increased,
whereas AKT1S1 is decreased, suggesting the activation of mTOR pathway.
Importantly, treatment of AZD8055, an mTOR inhibitor, leads to the decreased
phosphorylation levels of mTOR downstream molecules RPS6KB1 at Thr421/Ser424 and
AKT at Ser473. Furthermore, AZD8055 also preferentially reduces viability, and
inhibits migration and invasion abilities of the T-R cells. Together, our
findings indicate that mTOR pathway is among multiple signaling pathways that
mediate trastuzumab resistance in NCI N87 T-R cells, and that mTOR inhibitors may
be used to treat trastuzumab resistant, HER2-positive gastric cancer tumors.
PMID- 28507277
TI - Notch1 regulates the JNK signaling pathway and increases apoptosis in
hepatocellular carcinoma.
AB - Notch1-induced pathways are involved in cell growth, apoptosis, motility, and
invasion in many cancers. In the present study, the expression of Notch1 and
NICD1 was detected in hepatocellular carcinoma (HCC) tissues using in-vitro
assays. And then, we explored cell biology and signaling pathways using Notch1
siRNA or plasmids. Here, the expression of Notch1 and NICD1 was significantly
decreased in HCC tissues. In-vitro, Notch1 plasmids inhibited cell proliferation,
migration and invasion, but enhanced apoptosis of HepG2 and Hep3B cells.
Conversely, si-Notch1 enhanced cell proliferation, migration and invasion, but
inhibited apoptosis of HepG2 and Hep3B cells. Mechanically, Notch1 decreased the
expression of cyclin D1, MMP-9 and Bcl-2, but increased the expression of p-JNK,
Bax and cleaved caspase 3 in HepG2 and Hep3B cells. Besides, si-JNK or JNK
inhibitor SP600125 affected the activation of Notch1 signaling pathway, and
prevents cell apoptosis. In conclusion, Notch1 regulates the JNK signaling
pathway and increases apoptosis in HCC. Because patients with HCC have a poor
prognosis, Notch1 pathway may provide a novel treatment strategy.
PMID- 28507278
TI - Regulation of CD44v6 expression in gastric carcinoma by the IL-6/STAT3 signaling
pathway and its clinical significance.
AB - As a cancer stem cell marker, CD44 variant 6 (CD44v6) has been implicated in
carcinogenesis, tumor progression, and metastasis in a variety of human
carcinomas. However, little is known about the expression of CD44v6 in Gastric
Carcinoma (GC). Therefore we investigated CD44v6 expression in clinical specimen
and further explore the underlying molecular mechanisms.In this study, we
systemically investigated CD44v6 expression by immunohistochemistry in normal,
premalignant gastric mucosa (low and high grade intraepithelial neoplasia), and
GC at various stages. The correlation of CD44v6 expression with
clinicopathological characteristics, and prognosis in GC was also analyzed. Next,
we investigated cell proliferation, migration and invasion in GC cell lines.
Furthermore, we explored a novel mechanism by which CD44V6 was upregulated in GC
cell.The immunohistochemistry results showed that enhanced expression of CD44v6
was closely associated with tumor differentiation, lymph node metastasis, TNM
stage and poor prognosis in GC patients. In gastric cancer cell lines, CD44v6
involved in cell proliferation, invasion and metastasis in Next, report on a
novel mechanism by which interleukin-6/signal transducer and activator of
transcription 3 (IL-6/STAT3) signaling up-regulates expression of CD44v6. RNA
interference silencing of STAT3 resulted in decrease of CD44v6 levels. We also
found that STAT3 inhibitor AG490 decrease expression of CD44v6 by blocking
activation of STAT3, even in the presence of IL-6. Targeting STAT3-mediated
CD44v6 up-regulation may represent a novel, effective treatment by eradicating
the stomach tumor microenvironment.
PMID- 28507279
TI - Prognostic significance of soluble mesothelin in malignant pleural mesothelioma:
a meta-analysis.
AB - BACKGROUND: Soluble mesothelin is beneficial to detect the progression and the
treatment response of malignant pleural mesothelioma. However, the prognostic
value of soluble mesothelin in malignant pleural mesothelioma remains unclear.
METHODS: Hazard ratio with 95% CI was used to evaluate the prognostic value of
soluble mesothelin and the effect of clinicopathological characteristics on the
survival of malignant pleural mesothelioma. RESULTS: Eight eligible studies
involving 579 patients were selected for this meta-analysis. The results showed
that soluble mesothelin level was significantly correlated with the survival of
malignant pleural mesothelioma (pooled HR: 1.958, 95%CI: 1.531-2.504, p = 0.000;
heterogeneity test: I2 = 1.1%, p = 0.421). In addition, the survival of malignant
pleural mesothelioma was significantly correlated with some clinicopathological
characteristics such as tumor histology (HR = 3.214, 95% CI = 2.071-4.988, p =
0.000; heterogeneity test: I2 = 0.0%, p = 0.623) and tumor stage (HR = 2.007; 95%
CI = 1.477-2.727; p = 0.000; heterogeneity test: I2 = 0.0%, p = 0.966).
CONCLUSIONS: The survival of malignant pleural mesothelioma is significantly
correlated with tumor histology and tumor stage. Furthermore, high soluble
mesothelin level may lead to a poor prognosis for malignant pleural mesothelioma
patients.
PMID- 28507281
TI - High expression of long non-coding RNA NEAT1 indicates poor prognosis of human
cancer.
AB - The nuclear paraspeckle assembly transcript 1 (NEAT1) is a long non-coding RNA.
Many studies have reported that NEAT1 plays critical oncogenic roles and
facilitates tumorigenesis of various human cancers. High NEAT1 expression is
associated with a poor prognosis in cancer patients. This meta-analysis was
conducted to assess the association between NEAT1 levels and survival times of
cancer patients. Overall survival (OS) was the primary endpoint. Thirteen
publications with 1,496 cancer patients from 5 databases (PubMed, EMBASE,
Cochrane Library, Wiley Online Library, and Medline) met the criteria for this
meta-analysis. Results of the analysis showed that NEAT1 expression in human
cancer was significantly associated with OS (hazard ratio [HR]=1.53, 95%
confidence interval [CI]: 1.39-1.68), including digestive system tumor (HR=1.54,
95% CI: 1.37-1.73) and respiratory carcinomas (HR=1.44, 95% CI: 1.11-1.85). The
results also indicated that NEAT1 expression was highly associated with tumor
size (>3 cm vs. <=3 cm; odds ratio [OR]=2.51, 95% CI: 1.27-4.99; p=0.009), TNM
stage (III+IV vs. I+II; OR=4.17, 95% CI: 2.42-7.18; p=0.00001), and distant
metastasis (OR=2.73, 95% CI: 1.28-5.79; p=0.01). However, there was no
significant association with differentiation (poor vs. well + moderate, OR=1.45,
95% CI: 0.72-2.91) and lymph node metastasis (OR=1.39, 95% CI: 0.54-3.60). This
meta-analysis showed that NEAT1 expression may be a useful biomarker for
predicting a poor prognosis in patients with cancer.
PMID- 28507280
TI - Molecular dissection of effector mechanisms of RAS-mediated resistance to anti
EGFR antibody therapy.
AB - Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR),
cetuximab and panitumumab, are a mainstay of metastatic colorectal cancer (mCRC)
treatment. However, a significant number of patients suffer from primary or
acquired resistance. RAS mutations are negative predictors of clinical efficacy
of anti-EGFR antibodies in patients with mCRC. Oncogenic RAS activates the MAPK
and PI3K/AKT pathways, which are considered the main effectors of resistance.
However, the relative impact of these pathways in RAS-mutant CRC is less defined.
A better mechanistic understanding of RAS-mediated resistance may guide
development of rational intervention strategies. To this end we developed cancer
models for functional dissection of resistance to anti-EGFR therapy in vitro and
in vivo. To selectively activate MAPK- or AKT-signaling we expressed
conditionally activatable RAF-1 and AKT in cancer cells. We found that either
pathway independently protected sensitive cancer models against anti-EGFR
antibody treatment in vitro and in vivo. RAF-1- and AKT-mediated resistance was
associated with increased expression of anti-apoptotic BCL-2 proteins. Biomarkers
of MAPK and PI3K/AKT pathway activation correlated with inferior outcome in a
cohort of mCRC patients receiving cetuximab-based therapy. Dual pharmacologic
inhibition of PI3K and MEK successfully sensitized primary resistant CRC models
to anti-EGFR therapy. In conclusion, combined targeting of MAPK and PI3K/AKT
signaling, but not single pathways, may be required to enhance the efficacy of
anti-EGFR antibody therapy in patients with RAS-mutated CRC as well as in RAS
wild type tumors with clinical resistance.
PMID- 28507283
TI - MiR-149 Compromises the Reactions of Liver Cells to Fatty Acid via its
Polymorphism and Increases Non-Alcoholic Fatty Liver Disease (NAFLD) Risk by
Targeting Methylene Tetrahydrofolate Reductase (MTHFR).
AB - BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a worldwide health
problem, and microRNA (miRNA) has been reported to be involved in NAFLD. The
objective of our study was to explore the effect of polymorphism in miR-149 on
the pathogenesis of NAFLD. MATERIAL AND METHODS Real-time PCR was performed to
explore the effect of long-chain fatty acid (FFA) on the level of miR-149 and
methylene tetrahydrofolate reductase (MTHFR). Then in-silicon analysis and
luciferase assay were investigated to verify MTHFR was the target gene of miR
149. Finally, Western-blot analysis and real-time PCR were performed to confirm
the control of MTHFR by miR-149. RESULTS In this study, we found that miR-149 was
apparently upregulated in hepatocytes genotyped as TT treated with FFA; and MTHFR
in hepatocytes genotyped as TT treated with FFA was evidently downregulated
compared to control. Whereas, FFA had no obvious effect on MTHFR level in
hepatocytes genotyped as CC. We searched an online miRNA database and found that
miR-149 was a regulator of MTHFR expression, which was confirmed by luciferase
assay. In hepatocytes genotyped as TT and treated with or without FFA, miR-149
mimic dose-dependently decreased the level of MTHFR, and miR-149 inhibitor dose
dependently increased the level of MTHFR. And in hepatocytes genotyped as CC
treated with or without FFA exhibited a similar inhibition effect of miR-149 on
expression of MTHFR. CONCLUSIONS The data suggested that the polymorphism in miR
149 played an important role in the development of NAFLD via altering the
expression of miR-149 as well as its target, MTHFR.
PMID- 28507282
TI - P53 suppresses ribonucleotide reductase via inhibiting mTORC1.
AB - Balanced deoxyribonucleotides pools are essential for cell survival and genome
stability. Ribonucleotide reductase is the rate-limiting enzyme for the
production of deoxyribonucleotides. We report here that p53 suppresses
ribonucleotide reductase subunit 1 (RRM1) and 2 (RRM2) via inhibiting mammalian
target of rapamycin complex 1 (mTORC1). In vitro, cancer cell lines and mouse
embryonic fibroblast cells were treated with different concentrations of
pharmacological inhibitors for different times. In vivo, rhabdomyosarcoma Rh30
cell tumor-bearing mice were treated with rapamycin or AZD8055. Protein levels
and phosphorylation status were assessed by immunoblotting and mRNA levels were
determined by real time RT-PCR. Pharmacological inhibition of mTORC1 with
rapamycin, mTOR kinase with AZD8055 or protein kinase B with MK2206 resulted in
decrease of RRM1 and RRM2 in Rh30 cells both in vitro and in mouse tumor
xenografts. Moreover, eukaryotic translational initiation factor 4E-binding
proteins 1 and 2 double knockout mouse embryonic fibroblast cells demonstrated an
elevation of RRM1 and RRM2. Furthermore, down-regulation of mTOR-protein kinase B
signaling or cyclin dependent kinase 4 led to decrease of RRM1 and RRM2 mRNAs. In
addition, TP53 mutant cancer cells had elevation of RRM1 and RRM2, which was
reduced by rapamycin. Importantly, human double minute 2 inhibitor nutlin-3
decreased RRM1 and RRM2 in TP53 wild type rhabdomyosarcoma Rh18 but not in TP53
mutated Rh30 cells. Our data demonstrated that mTOR enhances the cap-dependent
protein translation and gene transcription of RRM1 and RRM2. Our findings might
provide an additional mechanism by which p53 maintains genome stability.
PMID- 28507284
TI - Melanoma Masquerading as a Zosteriform Rash.
AB - BACKGROUND Primary care physicians and internal medicine specialists frequently
encounter a variety of rashes. Many of these cases look and feel typical of
common entities, resulting in the potential for misdiagnosis. CASE REPORT This is
a case of a zosteriform rash where the surprising true diagnosis of metastatic
melanoma was confirmed with bedside skin punch biopsy. Possible mechanisms
involve direct cutaneous injury, neuronal, and dorsal root ganglia involvement in
metastases. CONCLUSIONS Skin biopsy is indispensable especially when there is a
lack of clinical response or deterioration in the clinical condition. The
pathophysiology of zosteriform metastasis is unclear.
PMID- 28507285
TI - Multivariate EEG analyses support high-resolution tracking of feature-based
attentional selection.
AB - The primary electrophysiological marker of feature-based selection is the N2pc, a
lateralized posterior negativity emerging around 180-200 ms. As it relies on
hemispheric differences, its ability to discriminate the locus of focal attention
is severely limited. Here we demonstrate that multivariate analyses of raw EEG
data provide a much more fine-grained spatial profile of feature-based target
selection. When training a pattern classifier to determine target position from
EEG, we were able to decode target positions on the vertical midline, which
cannot be achieved using standard N2pc methodology. Next, we used a forward
encoding model to construct a channel tuning function that describes the
continuous relationship between target position and multivariate EEG in an eight
position display. This model can spatially discriminate individual target
positions in these displays and is fully invertible, enabling us to construct
hypothetical topographic activation maps for target positions that were never
used. When tested against the real pattern of neural activity obtained from a
different group of subjects, the constructed maps from the forward model turned
out statistically indistinguishable, thus providing independent validation of our
model. Our findings demonstrate the power of multivariate EEG analysis to track
feature-based target selection with high spatial and temporal precision.
PMID- 28507286
TI - Complexes of DNA with fluorescent dyes are effective reagents for detection of
autoimmune antibodies.
AB - To date, there are multiple assays developed that detect and quantify antibodies
in biofluids. Nevertheless, there is still a lack of simple approaches that
specifically detect autoimmune antibodies to double-stranded DNA. Herein we
investigate the potential of novel nucleic acid complexes as targets for these
antibodies. This is done in a simple, rapid and specific immunofluorescence
assay. Specifically, employing 3D nanostructures (DNA origami), we present a new
approach in the detection and study of human antibodies to DNA. We demonstrate
the detection of anti-DNA antibodies that are characteristic of systemic lupus
erythematosus, a chronic autoimmune disease with multiple manifestations. We
tested the most potent non-covalent pairs of DNA and fluorescent dyes. Several
complexes showed specific recognition of autoimmune antibodies in human samples
of lupus patients using a simple one-step immunofluorescence method. This makes
the novel assay developed herein a promising tool for research and point-of-care
monitoring of anti-DNA antibodies. Using this method, we for the first time
experimentally confirm that the disease-specific autoimmune antibodies are
sensitive to the 3D structure of nucleic acids and not only to the nucleotide
sequence, as was previously thought.
PMID- 28507287
TI - Integrin beta8 (ITGB8) activates VAV-RAC1 signaling via FAK in the acquisition of
endometrial epithelial cell receptivity for blastocyst implantation.
AB - Integrin beta8 (ITGB8) is involved in the endometrial receptivity. The blastocyst
first interacts with the luminal endometrial epithelial cells during its
implantation; therefore, we have investigated the signaling of ITGB8 via FAK and
VAV-RAC1 in the endometrial epithelial cells. Integrin beta8 was found elevated
in epithelial cells at late-pre-receptive (day4, 1600 h) and receptive (day5,
0500 h) stages of endometrial receptivity period in the mouse. Integrins
downstream molecule FAK has demonstrated an increased expression and
phosphorylation (Y397) in the endometrium as well as in the isolated endometrial
epithelial cells during receptive and post-receptive stages. Integrin beta8 can
functionally interact with FAK, VAV and RAC1 as the levels of phosphorylated-FAK,
and VAV along with the RAC-GTP form was reduced after ITGB8 knockdown in the
endometrial epithelial cells and uterus. Further, VAV and RAC1 were seen poorly
active in the absence of FAK activity, suggesting a crosstalk of ITGB8 and FAK
for VAV and RAC1 activation in the endometrial epithelial cells. Silencing of
ITGB8 expression and inhibition of FAK activity in the Ishikawa cells rendered
poor attachment of JAr spheroids. In conclusion, ITGB8 activates VAV-RAC1
signaling axis via FAK to facilitate the endometrial epithelial cell receptivity
for the attachment of blastocyst.
PMID- 28507288
TI - Identifying individuals with physician-diagnosed chronic obstructive pulmonary
disease in primary care electronic medical records: a retrospective chart
abstraction study.
AB - : Little is known about using electronic medical records to identify patients
with chronic obstructive pulmonary disease to improve quality of care. Our
objective was to develop electronic medical record algorithms that can accurately
identify patients with obstructive pulmonary disease. A retrospective chart
abstraction study was conducted on data from the Electronic Medical Record
Administrative data Linked Database (EMRALD(r)) housed at the Institute for
Clinical Evaluative Sciences. Abstracted charts provided the reference standard
based on available physician-diagnoses, chronic obstructive pulmonary disease
specific medications, smoking history and pulmonary function testing. Chronic
obstructive pulmonary disease electronic medical record algorithms using
combinations of terminology in the cumulative patient profile (CPP; problem
list/past medical history), physician billing codes (chronic
bronchitis/emphysema/other chronic obstructive pulmonary disease), and
prescriptions, were tested against the reference standard. Sensitivity,
specificity, and positive/negative predictive values (PPV/NPV) were calculated.
There were 364 patients with chronic obstructive pulmonary disease identified in
a 5889 randomly sampled cohort aged >= 35 years (prevalence = 6.2%). The
electronic medical record algorithm consisting of >= 3 physician billing codes
for chronic obstructive pulmonary disease per year; documentation in the CPP;
tiotropium prescription; or ipratropium (or its formulations) prescription and a
chronic obstructive pulmonary disease billing code had sensitivity of 76.9% (95%
CI:72.2-81.2), specificity of 99.7% (99.5-99.8), PPV of 93.6% (90.3-96.1), and
NPV of 98.5% (98.1-98.8). Electronic medical record algorithms can accurately
identify patients with chronic obstructive pulmonary disease in primary care
records. They can be used to enable further studies in practice patterns and
chronic obstructive pulmonary disease management in primary care. CHRONIC LUNG
DISEASE: NOVEL ALGORITHM SEARCH TECHNIQUE: Researchers develop an algorithm that
can accurately search through electronic health records to find patients with
chronic lung disease. Mining population-wide data for information on patients
diagnosed and treated with chronic obstructive pulmonary disease (COPD) in
primary care could help inform future healthcare and spending practices. Theresa
Lee at the University of Toronto, Canada, and colleagues used an algorithm to
search electronic medical records and identify patients with COPD from doctors'
notes, prescriptions and symptom histories. They carefully adjusted the algorithm
to improve sensitivity and predictive value by adding details such as specific
medications, physician codes related to COPD, and different combinations of
terminology in doctors' notes. The team accurately identified 364 patients with
COPD in a randomly-selected cohort of 5889 people. Their results suggest
opportunities for broader, informative studies of COPD in wider populations.
PMID- 28507289
TI - Cells reprogramming to stem cells inhibit the reprogramming of adjacent cells in
the moss Physcomitrella patens.
AB - Under certain circumstances differentiated cells can be reprogrammed to form stem
cells in land plants, but only a portion of the cells reprograms successfully. A
long-distance inhibitory signal from reprogrammed cells to surrounding cells has
been reported in some ferns. Here we show the existence of anisotropic inhibitory
signal to regulate stem cell formation in the moss Physcomitrella patens. When
single cells were isolated from a gametophore leaf, over 90% of them were
reprogrammed to stem cells with characteristic nuclear expansion. By contrast,
when two adjacent cells were isolated, the nuclei of both cells expanded, but
successful reprogramming of both cells occurred only in approximately one fifth
of the pairs. When three aligned cells were isolated, the reprogramming rate of
both edge cells decreased with a living middle cell but did not with a dead
middle cell. Furthermore, unequal conversion into stem cells was more prominent
in cell pairs aligned parallel to the proximal-distal leaf axis than in those
perpendicular to the axis. This study gives an insight into the role of the
inhibitory signal in development and evolution as well as the efficient stem cell
induction from differentiated cells.
PMID- 28507290
TI - Effects of the non-parabolic kinetic energy on non-equilibrium polariton
condensates.
AB - In the study of non-equilibrium polariton condensates it is usually assumed that
the dispersion relation of polaritons is parabolic in nature. We show that
considering the true non-parabolic kinetic energy of polaritons leads to
significant changes in the behaviour of the condensate due to the curvature of
the dispersion relation and the possibility of transfer of energy to high
wavenumber components in the condensate spatial profile. We present explicit
solutions for plane waves and linear excitations, and identify the differences in
the theoretical predictions between the parabolic and non-parabolic mean-field
models, showing the possibility of symmetry breaking in the latter. We then
consider the evolution of wavepackets and show that self-localisation effects may
be observed due to the curvature of the dispersion relation. Finally, we revisit
the dynamics of dark soliton trains and show that additional localized density
excitations may emerge in the dynamics due to the excitation of high frequency
components, mimicking the appearance of near-bright solitary waves over short
timescales.
PMID- 28507291
TI - Construction of genotyping-by-sequencing based high-density genetic maps and QTL
mapping for fusarium wilt resistance in pigeonpea.
AB - Fusarium wilt (FW) is one of the most important biotic stresses causing yield
losses in pigeonpea. Genetic improvement of pigeonpea through genomics-assisted
breeding (GAB) is an economically feasible option for the development of high
yielding FW resistant genotypes. In this context, two recombinant inbred lines
(RILs) (ICPB 2049 * ICPL 99050 designated as PRIL_A and ICPL 20096 * ICPL 332
designated as PRIL_B) and one F2 (ICPL 85063 * ICPL 87119) populations were used
for the development of high density genetic maps. Genotyping-by-sequencing (GBS)
approach was used to identify and genotype SNPs in three mapping populations. As
a result, three high density genetic maps with 964, 1101 and 557 SNPs with an
average marker distance of 1.16, 0.84 and 2.60 cM were developed in PRIL_A,
PRIL_B and F2, respectively. Based on the multi-location and multi-year
phenotypic data of FW resistance a total of 14 quantitative trait loci (QTLs)
including six major QTLs explaining >10% phenotypic variance explained (PVE) were
identified. Comparative analysis across the populations has revealed three
important QTLs (qFW11.1, qFW11.2 and qFW11.3) with upto 56.45% PVE for FW
resistance. This is the first report of QTL mapping for FW resistance in
pigeonpea and identified genomic region could be utilized in GAB.
PMID- 28507292
TI - Growth, Properties, and Theoretical Analysis of M2LiVO4 (M = Rb, Cs) Crystals:
Two Potential Mid-Infrared Nonlinear Optical Materials.
AB - Mid-Infrared nonlinear optical (Mid-IR NLO) crystals with excellent performances
play a particularly important role for applications in areas such as
telecommunications, laser guidance, and explosives detection. However, the design
and growth of high performance Mid-IR NLO crystals with large NLO efficiency and
high laser-damage threshold (LDT) still face numerous fundamental challenge. In
this study, two potential Mid-IR NLO materials, Rb2LiVO4 (RLVO) and Cs2LiVO4
(CLVO) with noncentrosymmetric structures (Orthorhombic, Cmc21) were synthesized
by high-temperature solution method. Thermal analysis and powder X-ray
diffraction demonstrate that RLVO and CLVO melt congruently. Centimeter sized
crystals of CLVO have been grown by the top-seeded solution growth method. RLVO
and CLVO exhibit strong second harmonic generation (SHG) effects (about 4 and 5
times that of KH2PO4, respectively) with a phase-matching behavior at 1.064 MUm,
and a wide transparency range (0.33-6.0 MUm for CLVO). More importantly, RLVO and
CLVO possess a high LDT value (~28 * AgGaS2). In addition, the density functional
theory (DFT) and dipole moments studies indicate that the VO4 anionic groups have
a dominant contribution to the SHG effects in RLVO and CLVO. These results
suggest that the title compounds are promising NLO candidate crystals applied in
the Mid-IR region.
PMID- 28507293
TI - Exploring optoelectronic properties and mechanisms of layered ferroelectric
K4Nb6O17 nanocrystalline films and nanolaminas.
AB - Two-dimensional layered K4Nb6O17 (KN) was easily formed as a secondary phase
caused by the volatilization of alkali metal ions, when preparing ferroelectric K
x Na1-x NbO3 based ceramics and films. In this work, it was believed that KN film
is with weak ferroelectricity and has a little effect on the ferroelectric
properties of K x Na1-x NbO3 based films. Moreover, temperature dependent (77-500
K) dielectric functions of KN film have been firstly extracted by fitting
ellipsometric spectra with the Adachi dielectric function model and a four-phase
layered model. The high-frequency dielectric constant linearly increases and
optical band gap slightly decreases with increasing the temperature. We also
research its photoelectrochemical properties and its application in high
efficient light-induced H2 evolution. In addition, X-ray photoelectron
spectroscopy, Raman scattering, temperature dependent transmittance and infrared
reflectance spectra, and first-principles calculation were conjointly performed
to further reveal the intrinsic optoelectronic features and relevant mechanisms
of KN.
PMID- 28507295
TI - Self-assembled levitating clusters of water droplets: pattern-formation and
stability.
AB - Water forms ordered hexagonally symmetric structures (snow crystals) in its solid
state, however not as liquid. Typically, mists and clouds are composed of
randomly moving small droplets lacking any ordered structure. Self-organized
hexagonally patterned microdroplet clusters over locally heated water surfaces
have been recently observed. However, many aspects of the phenomenon are far from
being well understood including what determines droplets size, arrangement, and
the distance between them. Here we show that the Voronoi entropy of the cluster
tends to decrease indicating to their self-organization, while coupling of
thermal effects and mechanical forces controls the stability of the clusters. We
explain the balance of the long-range attraction and repulsion forces which
stabilizes the cluster patterns and established the range of parameters, for
which the clusters are stable. The cluster is a dissipative structure similar to
self-organized Rayleigh-Benard convective cells. Microdroplet formation plays a
role in a variety effects from mist and clouds to aerosols. We anticipate that
the discovery of the droplet cluster phenomenon and its explanation will provide
new insights on the fundamental physical and chemical processes such as
microdroplet role in reaction catalysis in nature as well as new tools for
aerosol analysis and microfluidic applications.
PMID- 28507294
TI - Laparoscopic versus opengastric surgery for the treatment of pathological T1N0M0
gastric cancer in elderly patients: a matched study.
AB - The aim of this study was to compare the outcomes of laparoscopic surgery (LAP)
and open gastric surgery (OP) in early gastric cancer patients aged >=70 years.We
conducted a retrospectively analysis among patientswith pathological T1N0M0
gastric cancer,who underwent LAP or OP between January 1, 2001 and December 31,
2008. We identified a well-balanced cohort of 2,360 patients (1180 patients in
each group). LAP has been shown to offer a superior perioperative results to OP,
including lower blood loss, shorter time to oral intake, walk and bowel function
recovery, shorter time of hospital stay, and less blood transfusion required.
However, the intraoperative and postoperative complications, local recurrence,
and metastasis didn't show statistically significant differences between groups.
The 5-year overall survival (OS), disease-free survival (DFS), and cancer
specific survival (CSS) were 60.1% vs.63.2%, 80.8% vs. 83.3%, and 87.6% vs. 89.5%
in the LAP group and OP group, respectively. The hazard ratios (HR) for OS, DFS,
and CSS were 1.09(95% confidence interval [CI]: 0.95-1.25; P = 0.215), 1.03(95%
CI: 0.91-1.18; P = 0.636), and 1.07 (95% CI: 0.88-1.30; P = 0.484), respectively,
compared LAP group with OP group. In conclusion, LAP is an acceptable alternative
to OP in elderly patients with early gastric cancer.
PMID- 28507296
TI - Sleep disorder, an independent risk associated with arterial stiffness in
menopause.
AB - As women age and go through menopause, they suffer a higher incidence of sleep
disorder, cardiovascular morbidity and mortality. In addition, evidences
suggested that sleep disorder was an important pathological indicator for
coronary heart disease. However, the relationship between different menopausal
status, sleep disorder and cardiovascular diseases was unclear. Thus, we aim to
assess the association between sleep disorder with arterial stiffness in females
of 40-60 years free of cardiovascular diseases through self-administered
Pittsburgh Sleep Quality Index (PSQI) and brachial-ankle pulse wave velocity
(baPWV). Logistic regression revealed that sleep disorder (PSQI score >= 8) was
an independent indicator for higher risk of elevated arterial stiffness (baPWV >=
1465.5 cm/s, upper tertile) beyond other established cardiovascular confounders
in peri-postmenopause (OR 2.83, 95% confidence interval (CI) 2.00-4.00, p <
0.001), but not in premenopause (OR 1.67, 95% CI 0.71-3.90, p = 0.223).
Collectively, it clearly indicates that sleep disorder in menopausal women is of
prominent value to predict arterial stiffness.
PMID- 28507297
TI - A One-Pot Three-Component Double-Click Method for Synthesis of [67Cu]-Labeled
Biomolecular Radiotherapeutics.
AB - A one-pot three-component double-click process for preparing tumor-targeting
agents for cancer radiotherapy is described here. By utilizing DOTA (or NOTA)
containing tetrazines and the TCO-substituted aldehyde, the two click reactions,
the tetrazine ligation (an inverse electron-demand Diels-Alder cycloaddition) and
the RIKEN click (a rapid 6pi-azaelectrocyclization), could simultaneously proceed
under mild conditions to afford covalent attachment of the metal chelator DOTA or
NOTA to biomolecules such as to albumin and anti-IGSF4 antibody without altering
their activities. Subsequently, radiolabeling of DOTA- or NOTA-attached albumin
and anti-IGSF4 antibody (an anti-tumor-targeting antibody) with [67Cu], a beta-
emitting radionuclide, could be achieved in a highly efficient manner via a
simple chelation with DOTA proving to be a more superior chelator than NOTA. Our
work provides a new and operationally simple method for introducing the [67Cu]
isotope even in large quantities to biomolecules, thereby representing an
important process for preparations of clinically relevant tumor-targeting agents
for radiotherapy.
PMID- 28507301
TI - Erratum: Molecular characterization reveals the complexity of previously
overlooked coral-exosymbiont interactions and the implications for coral-guild
ecology.
PMID- 28507298
TI - Protective effects of APOE e2 against disease progression in subcortical vascular
mild cognitive impairment patients: A three-year longitudinal study.
AB - Although the association between apolipoprotein E (APOE) genotype and disease
progression is well characterized in patients with Alzheimer's disease, such a
relationship is unknown in patients with subcortical vascular cognitive
impairment. We evaluated whether APOE genotype is associated with disease
progression in subcortical vascular mild cognitive impairment (svMCI) patients.
We prospectively recruited 72 svMCI patients (19 APOE4 carriers, 42 APOE3
homozygotes, and 11 APOE2 carriers). Patients were annually followed-up with
brain MRI and neuropsychological tests for three years and underwent a second
Pittsburgh compound B (PiB)-PET at a mean interval of 32.3 months. Amyloid-beta
burden was quantified by PiB standardized uptake value ratio (SUVR), and the
amount of small vessel disease was quantified by number of lacune and small
vessel disease score on MRI. We also measured cortical thickness. During the
three years of follow-up, compared to the APOE3 homozygotes, there was less
increase in PiB SUVR among APOE2 carriers (p = 0.023), while the APOE genotype
did not show significant effects on small vessel disease progression. APOE2
carriers also showed less cortical thinning (p = 0.023) and a slower rate of
cognitive decline (p = 0.009) compared to those with APOE3 homozygotes. Our
findings suggest that, in svMCI patients, APOE2 has protective effects against
amyloid-beta accumulation, cortical thinning, and cognitive decline.
PMID- 28507299
TI - The Fatty Acid beta-Oxidation Pathway is Activated by Leucine Deprivation in
HepG2 Cells: A Comparative Proteomics Study.
AB - Leucine (Leu) is a multifunctional essential amino acid that plays crucial role
in various cellular processes. However, the integral effect of Leu on the hepatic
proteome remains largely unknown. Here, we for the first time applied an isobaric
tags for relative and absolute quantification (iTRAQ)-based comparative
proteomics strategy to investigate the proteome alteration induced by Leu
deprivation in human hepatocellular carcinoma (HepG2) cells. A total of 4,111
proteins were quantified; 43 proteins were further identified as differentially
expressed proteins between the normal and Leu deprivation groups. Bioinformatics
analysis showed that the differentially expressed proteins were involved in
various metabolic processes, including amino acid and lipid metabolism, as well
as degradation of ethanol. Interestingly, several proteins involved in the fatty
acid beta-oxidation pathway, including ACSL1, ACADS, and ACOX1, were up-regulated
by Leu deprivation. In addition, Leu deprivation led to the reduction of cellular
triglycerides in HepG2 cells. These results reveal that the fatty acid beta
oxidation pathway is activated by Leu deprivation in HepG2 cells, and provide new
insights into the regulatory function of Leu in multiple cellular processes,
especially fatty acid metabolism.
PMID- 28507302
TI - Impedance self-matching ultra-narrow linewidth fiber resonator by use of a
tunable pi-phase-shifted FBG.
AB - In this paper, we present a novel ultra-narrow linewidth fiber resonator formed
by a tunable polarization maintaining (PM) pi-phase-shifted fiber Bragg grating
and a PM uniform fiber Bragg grating with a certain length of PM single mode
fiber patch cable between them. Theoretical prediction shows that this resonator
has ultra-narrow linewidth resonant peaks and is easy to realize impedance
matching. We experimentally obtain 3 MHz narrow linewidth impedance matched
resonant peak in a 7.3 m ultra-long passive fiber cavity. The impedance self
matching characteristic of this resonator also makes itself particularly suitable
for use in ultra-sensitive sensors, ultra-narrow band rejection optical filters
and fiber lasers applications.
PMID- 28507300
TI - Minimum toe clearance: probing the neural control of locomotion.
AB - Minimum toe clearance (MTC) occurs during a highly dynamic phase of the gait
cycle and is associated with the highest risk of unintentional contact with
obstacles or the ground. Age, cognitive function, attention and visual feedback
affect foot clearance but how these factors interact to influence MTC control is
not fully understood. We measured MTC in 121 healthy individuals aged 20-80 under
four treadmill walking conditions; normal walking, lower visual field restriction
and two Stroop colour/word naming tasks of two difficulty levels. Competition for
cognitive and attentional resources from the Stroop task resulted in
significantly lower mean MTC in older adults, with the difficult Stroop task
associated with a higher frequency of extremely low MTC values and subsequently
an increased modelled probability of tripping in this group. While older adults
responded to visual restriction by markedly skewing MTC distributions towards
higher values, this condition was also associated with frequent, extremely low
MTC values. We reveal task-specific, age-dependent patterns of MTC control in
healthy adults. Age-related differences are most pronounced during heavy,
distracting cognitive load. Analysis of critically-low MTC values during dual
task walking may have utility in the evaluation of locomotor control and fall
risk in older adults and patients with motor control deficits.
PMID- 28507303
TI - Silver Nanoparticles-Decorated Titanium Oxynitride Nanotube Arrays for Enhanced
Solar Fuel Generation.
AB - We demonstrate, for the first time, the synthesis of highly ordered titanium
oxynitride nanotube arrays sensitized with Ag nanoparticles (Ag/TiON) as an
attractive class of materials for visible-light-driven water splitting. The
nanostructure topology of TiO2, TiON and Ag/TiON was investigated using FESEM and
TEM. The X-ray photoelectron spectroscopy (XPS) and the energy dispersive X-ray
spectroscopy (EDS) analyses confirm the formation of the oxynitride structure.
Upon their use to split water photoelectrochemically under AM 1.5 G illumination
(100 mW/cm2, 0.1 M KOH), the titanium oxynitride nanotube array films showed
significant increase in the photocurrent (6 mA/cm2) compared to the TiO2
nanotubes counterpart (0.15 mA/cm2). Moreover, decorating the TiON nanotubes with
Ag nanoparticles (13 +/- 2 nm in size) resulted in exceptionally high
photocurrent reaching 14 mA/cm2 at 1.0 VSCE. This enhancement in the photocurrent
is related to the synergistic effects of Ag decoration, nitrogen doping, and the
unique structural properties of the fabricated nanotube arrays.
PMID- 28507304
TI - Thickness-dependent conductance in Sb2SeTe2 topological insulator nanosheets.
AB - The conductivity increases as thickness decreases in a series of Sb2SeTe2
topological insulator nanosheets with thickness ranging from 80 to 200 nm, where
the sheet conductance is proportional to the thickness. The corresponding sheet
conductance of the surface state is 8.7 e2/h which is consistent with the values
extracted from the temperature dependent Shubnikov-de Haas oscillations at high
magnetic fields. The extracted Fermi momentum is the same as the results from the
ARPES value, and the Berry phase is pi. These support that the thickness
dependent sheet conductance originates from the combination of the surface state
and the bulk state.
PMID- 28507305
TI - Overcoming thermal noise in non-volatile spin wave logic.
AB - Spin waves are propagating disturbances in magnetically ordered materials,
analogous to lattice waves in solid systems and are often described from a
quasiparticle point of view as magnons. The attractive advantages of Joule-heat
free transmission of information, utilization of the phase of the wave as an
additional degree of freedom and lower footprint area compared to conventional
charge-based devices have made spin waves or magnon spintronics a promising
candidate for beyond-CMOS wave-based computation. However, any practical
realization of an all-magnon based computing system must undergo the essential
steps of a careful selection of materials and demonstrate robustness with respect
to thermal noise or variability. Here, we aim at identifying suitable materials
and theoretically demonstrate the possibility of achieving error-free clocked non
volatile spin wave logic device, even in the presence of thermal noise and clock
jitter or clock skew.
PMID- 28507306
TI - Long-term increases in soil carbon due to ecosystem fertilization by atmospheric
nitrogen deposition demonstrated by regional-scale modelling and observations.
AB - Fertilization of nitrogen (N)-limited ecosystems by anthropogenic atmospheric
nitrogen deposition (Ndep) may promote CO2 removal from the atmosphere, thereby
buffering human effects on global radiative forcing. We used the biogeochemical
ecosystem model N14CP, which considers interactions among C (carbon), N and P
(phosphorus), driven by a new reconstruction of historical Ndep, to assess the
responses of soil organic carbon (SOC) stocks in British semi-natural landscapes
to anthropogenic change. We calculate that increased net primary production due
to Ndep has enhanced detrital inputs of C to soils, causing an average increase
of 1.2 kgCm-2 (c. 10%) in soil SOC over the period 1750-2010. The simulation
results are consistent with observed changes in topsoil SOC concentration in the
late 20th Century, derived from sample-resample measurements at nearly 2000 field
sites. More than half (57%) of the additional topsoil SOC is predicted to have a
short turnover time (c. 20 years), and will therefore be sensitive to future
changes in Ndep. The results are the first to validate model predictions of Ndep
effects against observations of SOC at a regional field scale. They demonstrate
the importance of long-term macronutrient interactions and the transitory nature
of soil responses in the terrestrial C cycle.
PMID- 28507307
TI - A Novel Indication for Panobinostat as a Senolytic Drug in NSCLC and HNSCC.
AB - Panobinostat (pano) is an FDA-approved histone deacetylase inhibitor. There is
interest in evaluating alternate dosing schedules and novel combinations of pano
for the treatment of upper aerodigestive and lung malignancies; thus we evaluated
it in combination with Taxol, a chemotherapeutic with activity in both diseases.
Dose-dependent synergy was observed in Non-Small Cell Lung Cancer (NSCLC) and
Head and Neck Squamous Cell Carcinoma (HNSCC) cell lines and was due to
senescence rather than potentiation of cell death. Senescence occurred following
cisplatin- or Taxol-treatment in cell lines from both cancer types and was
associated with decreased histone 3 (H3) acetylation and increased Bcl-xL
expression: the latter a biomarker of senescence and target of anti-senescence
therapeutics, or senolytics. Since H3 acetylation and Bcl-xL expression were
altered in senescence, we subsequently evaluated pano as a senolytic in
chemotherapy-treated cancer cells enriched for senescent cells. Pano caused cell
death at significantly higher rates compared to repeat dosing with chemotherapy.
This was associated with decreased expression of Bcl-xL and increased acetylated
H3, reversing the expression patterns observed in senescence. These data support
evaluating pano as a post-chemotherapy senolytic with the potential to kill
persistent senescent cells that accumulate during standard chemotherapy in NSCLC
and HNSCC.
PMID- 28507308
TI - Barriers to breastfeeding in Lebanon: A policy analysis.
AB - Although the issue of breastfeeding in Lebanon has risen on the political agenda,
the country does not meet international recommendations for early breastfeeding
practices. This study analysed barriers to dissemination, implementation, and
enforcement of key policies to improve early breastfeeding practices. We
conducted interviews with stakeholders in breastfeeding policy in Lebanon and
used a framework approach for analysing data. We found a disconnect between
policy endorsement and translation on the ground, weak engagement of professional
associations and governmental institutions, undue influence by the breast milk
substitute industry, and competing priorities-most notably the current refugee
crisis. This study highlights the potential policy opportunities to counter these
barriers and points to the role of international organisations and grassroots
advocacy in pushing, monitoring, and implementing policies that protect
breastfeeding, where government capacity is limited, and the private sector is
strong.
PMID- 28507309
TI - PICK1 Genetic Variation and Cognitive Function in Patients with Schizophrenia.
AB - The gene of protein interacting with C kinase 1 alpha (PICK1) has been implicated
in schizophrenia, nevertheless, conflicting results existed. However, its role in
cognitive function remains unclear. Besides, cognitive deficits impair the long
term outcome. We explored whether the polymorphisms of PICK1 (rs2076369, rs3952)
affected cognitive functions in schizophrenic patients. We analyzed 302 patients
and tested the differences of cognitive functions, clinical symptoms between
genetic groups. We also used general linear model to analyze the effect of PICK1
genetic polymorphisms on cognitive functions. After adjustment for gender, age,
education, the patients with rs2076369 G/T genotype showed better performance
than T/T homozygotes in the summary score, global composite score, neurocognitive
composite score, category fluency subtest, WAIS-III-Digit Symbol Coding subtest,
working memory, WMS-III-Spatial Span (backward) subtest, MSCEIT-managing emotions
branch (p = 0.038, 0.025, 0.046, 0.036, 0.025, 0.027, 0.035, 0.028,
respectively). G/G homozygotes performed better than T/T in category fluency
subtest (p = 0.049). A/A homozygotes of rs3952 performed better than G/G in trail
making A subtest (p = 0.048). To our knowledge, this is the first study to
indicate that PICK1 polymorphisms may associate with cognitive functions in
schizophrenic patients. Further replication studies in healthy controls or other
ethnic groups are warranted.
PMID- 28507310
TI - Molecular and functional characterization of the BMPR2 gene in Pulmonary Arterial
Hypertension.
AB - Pulmonary arterial hypertension is a progressive disease that causes the
obstruction of precapillary pulmonary arteries and a sustained increase in
pulmonary vascular resistance. The aim was to analyze functionally the variants
found in the BMPR2 gene and to establish a genotype-phenotype correlation. mRNA
expression studies were performed using pSPL3 vector, studies of subcellular
localization were performed using pEGFP-N1 vector and luciferase assays were
performed using pGL3-Basic vector. We have identified 30 variants in the BMPR2
gene in 27 of 55 patients. In 16 patients we detected pathogenic mutations.
Minigene assays revealed that 6 variants (synonymous, missense) result in
splicing defect. By immunofluorescence assay, we observed that 4 mutations affect
the protein localization. Finally, 4 mutations located in the 5'UTR region showed
a decreased transcriptional activity in luciferase assays. Genotype-phenotype
correlation, revealed that patients with pathogenic mutations have a more severe
phenotype (sPaP p = 0.042, 6MWT p = 0.041), a lower age at diagnosis (p = 0.040)
and seemed to have worse response to phosphodiesterase-5-inhibitors (p = 0.010).
Our study confirms that in vitro expression analysis is a suitable approach in
order to investigate the phenotypic consequences of the nucleotide variants,
especially in cases where the involved genes have a pattern of expression in
tissues of difficult access.
PMID- 28507311
TI - Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and
sensitizes DDP treatment.
AB - Deregulated Sonic Hedgehog (SHH) pathway facilitates the initiation, progression,
and metastasis of Non-small cell lung cancer (NSCLC), confers drug resistance and
renders a therapeutic interference option to lung cancer patients with poor
prognosis. In this study, we screened and evaluated the specificity of a Chinese
herb Scutellariabarbata D. Don extraction (SBE) in repressing SHH signaling
pathway to block NSCLC progression. Our study confirmed that aberrant activation
of the SHH signal pathway conferred more proliferative and invasive phenotypes to
human lung cancer cells. This study revealed that SBE specifically repressed SHH
signaling pathway to interfere the SHH-mediated NSCLC progression and metastasis
via arresting cell cycle progression. We also found that SBE significantly
sensitized lung cancer cells to chemotherapeutic agent DDP via repressing SHH
components in vitro and in vivo. Mechanistic investigations indicated that SBE
transcriptionally and specifically downregulated SMO and consequently attenuated
the activities of GLI1 and its downstream targets in SHH signaling pathway, which
interacted with cell cycle checkpoint enzymes to arrest cell cycle progression
and lead to cellular growth inhibition and migration blockade. Collectively, our
results suggest SBE as a novel drug candidate for NSCLC which specifically and
sensitively targets SHH signaling pathway.
PMID- 28507312
TI - Design and evaluation of EphrinA1 mutants with cerebral protective effect.
AB - The activation of EphA2 receptor by its natural ligand EphrinA1 causes blood
brain barrier dysfunction, and inactivation of EphA2 reduces BBB damage in
ischemic stroke. Thus, EphA2 targeted antagonists may serve as neuroprotective
agents. We engineered four mutants of EphrinA1, EM1, EM2, EM3 and EM4,
respectively. The computational analysis showed that these four mutants were
capable of interacting with EphA2. Their potential neuroprotective effects were
examined in mouse focal ischemia/reperfusion (I/R) model. EM2 exhibited strong
neuroprotective effects, including reduced brain infarct volume, neuronal
apoptosis, cerebral edema, and improved neurological scores. The EM2-mediated
protection was associated with a comparative decrease in BBB leakage,
inflammatory infiltration, and higher expression levels of tight junction
proteins, such as zonula occludens-1 and Occludin. I/R-induced high expression of
Rho-associated protein kinase 2 (ROCK2) was down-regulated after EM2 treatment.
Moreover, EM2 reduced agonist doxazosin-induced EphA2 phosphorylation and cells
rounding in PC3 cells, indicating EphA2-antagonizing activity of EM2. These
finding provided evidences of the neuroprotection of EphA2 antagonist and a novel
approach for ischemic stroke treatment. These results also suggested that a
receptor agonist can be switched to an antagonist by substituting one or more
relevant residues.
PMID- 28507313
TI - Chronic intrahypothalamic rather than subcutaneous liraglutide treatment reduces
body weight gain and stimulates the melanocortin receptor system.
AB - BACKGROUND: The GLP-1 receptor agonist liraglutide is marketed for obesity
treatment where it induces body weight reduction possibly via the hypothalamus,
which regulates energy homeostasis. In animal studies, acute liraglutide
treatment triggers satiety, weight loss and activates thermogenesis in adipose
tissue. However, the precise mechanisms how liraglutide affects in particular
chronic weight loss are still under investigation. OBJECTIVES: We aimed to
evaluate whether chronic hypothalamic or chronic subcutaneous administration of
liraglutide induces sustained weight loss through altered adipose tissue function
and to what extent hypothalamic neuronal appetite regulators are involved in the
liraglutide-induced weight loss in healthy lean rats on a normal diet.
MATERIALS/METHODS: We continuously administered liraglutide either
intrahypothalamically (10 MUg per day) or subcutaneously (200 MUg kg-1 per day)
for 28 days to lean Sprague Dawley rats (n=8 each). We assessed changes in body
weight, adipose tissue mass, adipocyte size and adipose tissue volume in the
abdominal region by using micro-CT. We analyzed genetic expression patterns of
browning, thermogenic and adipocyte differentiation regulators in adipose tissues
as well as particular neuronal appetite regulators in the hypothalamus. RESULTS:
Intrahypothalamic liraglutide administration induced an 8% body weight reduction
at day 9 compared with the control group (P<0.01) and a 7% body weight loss at
day 9 compared with subcutaneous liraglutide treatment (P<0.01), supported by a
significant reduction in adipose tissue mass and volume with intrahypothalamic
liraglutide administration (P<0.05). Our data show that chronic intrahypothalamic
liraglutide treatment triggered an 18-fold induction of the hypothalamic mc4r
gene (P<0.01) accompanied by a significant increase in circulating thyroxine (T4)
levels (P<0.05). CONCLUSIONS: Chronic intrahypothalamic liraglutide
administration resulted in a profound reduction in body weight and fat mass loss
most likely mediated by the hypothalamic melanocortin system rather than by
adipose tissue browning or improved thermogenesis.
PMID- 28507314
TI - Metabolic imaging of energy metabolism in traumatic brain injury using
hyperpolarized [1-13C]pyruvate.
AB - Traumatic brain injury (TBI) is known to cause perturbations in the energy
metabolism of the brain, but current tests of metabolic activity are only
indirect markers of energy use or are highly invasive. Here we show that
hyperpolarized 13C magnetic resonance spectroscopic imaging (MRSI) can be used as
a direct, non-invasive method for studying the effects of TBI on energy
metabolism. Measurements were performed on rats with moderate TBI induced by
controlled cortical impact on one cerebral hemisphere. Following injection of
hyperpolarized [1-13C]pyruvate, the resulting 13C-bicarbonate signal was found to
be 24 +/- 6% lower in the injured hemisphere compared with the non-injured
hemisphere, while the hyperpolarized bicarbonate-to-lactate ratio was 33 +/- 8%
lower in the injured hemisphere. In a control group, no significant difference in
signal was found between sides of the brain. The results suggest an impairment in
mitochondrial pyruvate metabolism, resulting in a decrease in aerobic respiration
at the location of injury following TBI.
PMID- 28507315
TI - The Herpesvirus Nuclear Egress Complex Component, UL31, Can Be Recruited to Sites
of DNA Damage Through Poly-ADP Ribose Binding.
AB - The herpes simplex virus (HSV) UL31 gene encodes a conserved member of the
herpesvirus nuclear egress complex that not only functions in the egress of DNA
containing capsids from the nucleus, but is also required for optimal replication
of viral DNA and its packaging into capsids. Here we report that the UL31 protein
from HSV-2 can be recruited to sites of DNA damage by sequences found in its N
terminus. The N-terminus of UL31 contains sequences resembling a poly (ADP
ribose) (PAR) binding motif suggesting that PAR interactions might mediate UL31
recruitment to damaged DNA. Whereas PAR polymerase inhibition prevented UL31
recruitment to damaged DNA, inhibition of signaling through the ataxia
telangiectasia mutated DNA damage response pathway had no effect. These findings
were further supported by experiments demonstrating direct and specific
interaction between HSV-2 UL31 and PAR using purified components. This study
reveals a previously unrecognized function for UL31 and may suggest that the
recognition of PAR by UL31 is coupled to the nuclear egress of herpesvirus
capsids, influences viral DNA replication and packaging, or possibly modulates
the DNA damage response mounted by virally infected cells.
PMID- 28507316
TI - Autism spectrum disorders and autistic traits share genetics and biology.
AB - Autism spectrum disorders (ASDs) and autistic traits in the general population
may share genetic susceptibility factors. In this study, we investigated such
potential overlap based on common genetic variants. We developed and validated a
self-report questionnaire of autistic traits in adults. We then conducted genome
wide association studies (GWASs) of six trait scores derived from the
questionnaire through exploratory factor analysis in 1981 adults from the general
population. Using the results from the Psychiatric Genomics Consortium GWAS of
ASDs, we observed genetic sharing between ASDs and the autistic traits 'childhood
behavior', 'rigidity' and 'attention to detail'. Gene-set analysis subsequently
identified 'rigidity' to be significantly associated with a network of ASD gene
encoded proteins that regulates neurite outgrowth. Gene-wide association with the
well-established ASD gene MET reached significance. Taken together, our findings
provide evidence for an overlapping genetic and biological etiology underlying
ASDs and autistic population traits, which suggests that genetic studies in the
general population may yield novel ASD genes.
PMID- 28507317
TI - Elevation of p11 in lateral habenula mediates depression-like behavior.
AB - The lateral habenula (LHb) is a key brain region involved in the pathophysiology
of depression. It is activated by stimuli associated with negative experiences
and is involved in encoding aversive signals. Hyperactivity of LHb is found in
both rodent models of depression and human patients with depression. However,
little is known about the underlying molecular mechanisms. Here we show that in
LHb neurons, p11, a multifunctional protein implicated in depression, is
significantly upregulated by chronic restraint stress. Knockdown of p11
expression in LHb alleviates the stress-induced depression-like behaviors.
Moreover, chronic restraint stress induces bursting action potentials in LHb
neurons, which are abolished by p11 knockdown. Overexpression of p11 in dopamine
D2 receptor-containing LHb neurons of control mice induces depression-like
behaviors. These results have identified p11 in LHb as a key molecular
determinant regulating negative emotions, which may help to understand the
molecular and cellular basis of depression.
PMID- 28507319
TI - Longitudinal changes of tau PET imaging in relation to hypometabolism in
prodromal and Alzheimer's disease dementia.
AB - The development of tau-specific positron emission tomography (PET) tracers allows
imaging in vivo the regional load of tau pathology in Alzheimer's disease (AD)
and other tauopathies. Eighteen patients with baseline investigations enroled in
a 17-month follow-up study, including 16 with AD (10 had mild cognitive
impairment and a positive amyloid PET scan, that is, prodromal AD, and six had AD
dementia) and two with corticobasal syndrome. All patients underwent PET scans
with [18F]THK5317 (tau deposition) and [18F]FDG (glucose metabolism) at baseline
and follow-up, neuropsychological assessment at baseline and follow-up and a scan
with [11C]PIB (amyloid-beta deposition) at baseline only. At a group level,
patients with AD (prodromal or dementia) showed unchanged [18F]THK5317 retention
over time, in contrast to significant decreases in [18F]FDG uptake in
temporoparietal areas. The pattern of changes in [18F]THK5317 retention was
heterogeneous across all patients, with qualitative differences both between the
two AD groups (prodromal and dementia) and among individual patients. High
[18F]THK5317 retention was significantly associated over time with low episodic
memory encoding scores, while low [18F]FDG uptake was significantly associated
over time with both low global cognition and episodic memory encoding scores.
Both patients with corticobasal syndrome had a negative [11C]PIB scan, high
[18F]THK5317 retention with a different regional distribution from that in AD,
and a homogeneous pattern of increased [18F]THK5317 retention in the basal
ganglia over time. These findings highlight the heterogeneous propagation of tau
pathology among patients with symptomatic AD, in contrast to the homogeneous
changes seen in glucose metabolism, which better tracked clinical progression.
PMID- 28507318
TI - Cerebellar volume and cerebellocerebral structural covariance in schizophrenia: a
multisite mega-analysis of 983 patients and 1349 healthy controls.
AB - Although cerebellar involvement across a wide range of cognitive and
neuropsychiatric phenotypes is increasingly being recognized, previous large
scale studies in schizophrenia (SZ) have primarily focused on supratentorial
structures. Hence, the across-sample reproducibility, regional distribution,
associations with cerebrocortical morphology and effect sizes of cerebellar
relative to cerebral morphological differences in SZ are unknown. We addressed
these questions in 983 patients with SZ spectrum disorders and 1349 healthy
controls (HCs) from 14 international samples, using state-of-the-art image
analysis pipelines optimized for both the cerebellum and the cerebrum. Results
showed that total cerebellar grey matter volume was robustly reduced in SZ
relative to HCs (Cohens's d=-0.35), with the strongest effects in cerebellar
regions showing functional connectivity with frontoparietal cortices (d=-0.40).
Effect sizes for cerebellar volumes were similar to the most consistently
reported cerebral structural changes in SZ (e.g., hippocampus volume and
frontotemporal cortical thickness), and were highly consistent across samples.
Within groups, we further observed positive correlations between cerebellar
volume and cerebral cortical thickness in frontotemporal regions (i.e.,
overlapping with areas that also showed reductions in SZ). This cerebellocerebral
structural covariance was strongest in SZ, suggesting common underlying disease
processes jointly affecting the cerebellum and the cerebrum. Finally, cerebellar
volume reduction in SZ was highly consistent across the included age span (16-66
years) and present already in the youngest patients, a finding that is more
consistent with neurodevelopmental than neurodegenerative etiology. Taken
together, these novel findings establish the cerebellum as a key node in the
distributed brain networks underlying SZ.
PMID- 28507320
TI - The microbiome regulates amygdala-dependent fear recall.
AB - The amygdala is a key brain region that is critically involved in the processing
and expression of anxiety and fear-related signals. In parallel, a growing number
of preclinical and human studies have implicated the microbiome-gut-brain in
regulating anxiety and stress-related responses. However, the role of the
microbiome in fear-related behaviours is unclear. To this end we investigated the
importance of the host microbiome on amygdala-dependent behavioural readouts
using the cued fear conditioning paradigm. We also assessed changes in neuronal
transcription and post-transcriptional regulation in the amygdala of naive and
stimulated germ-free (GF) mice, using a genome-wide transcriptome profiling
approach. Our results reveal that GF mice display reduced freezing during the
cued memory retention test. Moreover, we demonstrate that under baseline
conditions, GF mice display altered transcriptional profile with a marked
increase in immediate-early genes (for example, Fos, Egr2, Fosb, Arc) as well as
genes implicated in neural activity, synaptic transmission and nervous system
development. We also found a predicted interaction between mRNA and specific
microRNAs that are differentially regulated in GF mice. Interestingly, colonized
GF mice (ex-GF) were behaviourally comparable to conventionally raised (CON)
mice. Together, our data demonstrates a unique transcriptional response in GF
animals, likely because of already elevated levels of immediate-early gene
expression and the potentially underlying neuronal hyperactivity that in turn
primes the amygdala for a different transcriptional response. Thus, we
demonstrate for what is to our knowledge the first time that the presence of the
host microbiome is crucial for the appropriate behavioural response during
amygdala-dependent memory retention.
PMID- 28507321
TI - PET imaging of dopamine-D2 receptor internalization in schizophrenia.
AB - Recent genetic, molecular and post-mortem studies suggest impaired dopamine (DA)
D2 receptor (D2R) trafficking in patients with schizophrenia (SZ). Imaging and
preclinical studies have shown agonist-induced D2R internalization can be imaged
with positron emission tomography (PET) using D2R radiotracers combined with
psychostimulant challenge. This is feasible if radiotracer binding is measured
when postchallenge DA levels have returned to baseline, following the initial
competition phase between DA and radiotracer for binding to D2R. Here we used
'late-phase' imaging after challenge to test the hypothesis that impaired D2R
internalization in SZ leads to blunted late-phase displacement, or a faster
return to baseline, in patients compared with healthy controls (HCs). We imaged
10 patients with SZ and 9 HCs with PET and [11C]raclopride at baseline and two
times (3-5 and 6-10 h) following 0.5 mg kg-1 dextroamphetamine. We measured
binding potential relative to non-displaceable compartment (BPND) and derived
percent reduction from baseline (DeltaBPND) for each postamphetamine scan. To
test the hypothesis that time course of return of striatal BPND to baseline
differed between SZ and HCs, we implemented a linear model with DeltaBPND as
dependent variable, time after amphetamine as repeated measure and time after
amphetamine and diagnostic group as fixed effects. Neither diagnostic group nor
interaction of diagnostic group-by-time after amphetamine significantly affected
striatal DeltaBPND (F=1.38, P=0.26; F=0.51, P=0.61). These results show similar
pattern of return of BPND to baseline as a function of time in patients with SZ
and HC, suggesting that striatal D2R internalization as measured by our imaging
paradigm is normal in patients with SZ.
PMID- 28507323
TI - Increasing phenological asynchrony between spring green-up and arrival of
migratory birds.
AB - Consistent with a warming climate, birds are shifting the timing of their
migrations, but it remains unclear to what extent these shifts have kept pace
with the changing environment. Because bird migration is primarily cued by
annually consistent physiological responses to photoperiod, but conditions at
their breeding grounds depend on annually variable climate, bird arrival and
climate-driven spring events would diverge. We combined satellite and citizen
science data to estimate rates of change in phenological interval between spring
green-up and migratory arrival for 48 breeding passerine species across North
America. Both arrival and green-up changed over time, usually in the same
direction (earlier or later). Although birds adjusted their arrival dates, 9 of
48 species did not keep pace with rapidly changing green-up and across all
species the interval between arrival and green-up increased by over half a day
per year. As green-up became earlier in the east, arrival of eastern breeding
species increasingly lagged behind green-up, whereas in the west-where green-up
typically became later-birds arrived increasingly earlier relative to green-up.
Our results highlight that phenologies of species and trophic levels can shift at
different rates, potentially leading to phenological mismatches with negative
fitness consequences.
PMID- 28507322
TI - Rapid susceptibility profiling of carbapenem-resistant Klebsiella pneumoniae.
AB - The expanding global distribution of multi-resistant Klebsiella pneumoniae
demands faster antimicrobial susceptibility testing (AST) to guide antibiotic
treatment. Current ASTs rely on time-consuming differentiation of resistance and
susceptibility after initial isolation of bacteria from a clinical specimen. Here
we describe a flow cytometry workflow to determine carbapenem susceptibility from
bacterial cell characteristics in an international K. pneumoniae isolate
collection (n = 48), with a range of carbapenemases. Our flow cytometry-assisted
susceptibility test (FAST) method combines rapid qualitative susceptible/non
susceptible classification and quantitative MIC measurement in a single process
completed shortly after receipt of a primary isolate (54 and 158 minutes
respectively). The qualitative FAST results and FAST-derived MIC (MICFAST)
correspond closely with broth microdilution MIC (MICBMD, Matthew's correlation
coefficient 0.887), align with the international AST standard (ISO 200776-1;
2006) and could be used for rapid determination of antimicrobial susceptibility
in a wider range of Gram negative and Gram positive bacteria.
PMID- 28507325
TI - Corrigendum: Characterisation of mental health conditions in social media using
Informed Deep Learning.
PMID- 28507326
TI - Tunability of Band Gap and Photoluminescence in CH3NH3PbI3 Films by Anodized
Aluminum Oxide Templates.
AB - Hybrid organic-inorganic halide CH3NH3PbI3 perovskite films are deposited on
anodized aluminum oxide templates with the different pore diameters via one-step
spin coating method. The obvious 0.082 eV blue shift of optical band gap is
observed in films with decreasing the diameters of pores from 400 to 30 nm. And
numerical simulations based on finite element modeling are carried out to
represent the absorption edge and consistent with the experiment results. It is
interesting that the films show the intense photoluminescence with the excitation
intensity of less than 1 MUW. Moreover, the photoluminescence intensity is
increased with increasing pore diameters, which is attributed to the radiative
recombination rate of photogenerated electrons and holes. These results pave a
way for the further understanding of tunable photophysical properties of
perovskite films.
PMID- 28507324
TI - A novel indole compound MA-35 attenuates renal fibrosis by inhibiting both TNF
alpha and TGF-beta1 pathways.
AB - Renal fibrosis is closely related to chronic inflammation and is under the
control of epigenetic regulations. Because the signaling of transforming growth
factor-beta1 (TGF-beta1) and tumor necrosis factor-alpha (TNF-alpha) play key
roles in progression of renal fibrosis, dual blockade of TGF-beta1 and TNF-alpha
is desired as its therapeutic approach. Here we screened small molecules showing
anti-TNF-alpha activity in the compound library of indole derivatives. 11 out of
41 indole derivatives inhibited the TNF-alpha effect. Among them, Mitochonic Acid
35 (MA-35), 5-(3, 5-dimethoxybenzyloxy)-3-indoleacetic acid, showed the potent
effect. The anti-TNF-alpha activity was mediated by inhibiting IkappaB kinase
phosphorylation, which attenuated the LPS/GaIN-induced hepatic inflammation in
the mice. Additionally, MA-35 concurrently showed an anti-TGF-beta1 effect by
inhibiting Smad3 phosphorylation, resulting in the downregulation of TGF-beta1
induced fibrotic gene expression. In unilateral ureter obstructed mouse kidney,
which is a renal fibrosis model, MA-35 attenuated renal inflammation and fibrosis
with the downregulation of inflammatory cytokines and fibrotic gene expressions.
Furthermore, MA-35 inhibited TGF-beta1-induced H3K4me1 histone modification of
the fibrotic gene promoter, leading to a decrease in the fibrotic gene
expression. MA-35 affects multiple signaling pathways involved in the fibrosis
and may recover epigenetic modification; therefore, it could possibly be a novel
therapeutic drug for fibrosis.
PMID- 28507327
TI - PDE3 inhibitor and EGCG combination treatment suppress cancer stem cell
properties in pancreatic ductal adenocarcinoma.
AB - Recurrence following chemotherapy is observed in the majority of patients with
pancreatic ductal adenocarcinoma (PDAC). Recent studies suggest that cancer stem
cells (CSCs) may be involved in PDAC recurrence and metastasis. However, an
efficient approach to targeting pancreatic CSCs remains to be established. Here
we show that in cancer cells overexpressing the 67-kDa laminin receptor (67LR)
dependent cyclic GMP (cGMP) inducer, epigallocatechin-3-O-gallate (EGCG) and a
phosphodiesterase 3 (PDE3) inhibitor in combination significantly suppressed the
Forkhead box O3 and CD44 axis, which is indispensable for the CSC properties of
PDAC. We confirmed that the EGCG and PDE3 inhibitor in combination strongly
suppressed tumour formation and liver metastasis in vivo. We also found that a
synthesized EGCG analog capable of inducing strong cGMP production drastically
suppressed the CSC properties of PDAC and extended the survival period in vivo.
In conclusion, the combination treatment of EGCG and a PDE3 inhibitor as a strong
cGMP inducer could be a potential treatment candidate for the eradication of CSCs
of PDAC.
PMID- 28507328
TI - Pro-inflammatory Ca++-activated K+ channels are inhibited by hydroxychloroquine.
AB - Antimalarials have demonstrated beneficial effects in Systemic Lupus
Erithematosus and Rheumatoid Arthritis. However, the mechanisms and the molecular
players targeted by these drugs remain obscure. Although hydroxychloroquine (HCQ)
is a known ion channel inhibitor, this property has not been linked to its anti
inflammatory effects. We aimed to study whether HCQ inhibits pro-inflammatory ion
channels. Electrophysiology experiments demonstrated that HCQ inhibited Ca++
activated K+ conductance in THP-1 macrophages in a dose-dependent manner. In
macrophages, ATP-induced K+ efflux plays a key role in activating the NLRP3
inflammasome. ATP-induced IL-1beta secretion was controlled by the KCa1.1
inhibitor iberiotoxin. NS1619 and NS309 (KCa1.1 and KCa3.1 activators
respectively) induced the secretion of IL-1beta. This effect was inhibited by HCQ
and also by iberiotoxin and clotrimazol (KCa3.1 inhibitor), arguing against off
target effect. In vitro, HCQ inhibited IL-1beta and caspase 1 activation induced
by ATP in a dose-dependent manner. HCQ impaired K+ efflux induced by ATP. In
vivo, HCQ inhibited caspase 1-dependent ATP-induced neutrophil recruitment. Our
results show that HCQ inhibits Ca++-activated K+ channels. This effect may lead
to impaired inflammasome activation. These results are the basis for i) a novel
anti-inflammatory mechanism for HCQ and ii) a new strategy to target pro
rheumatic Ca++-activated K+ channels.
PMID- 28507329
TI - Breeding histories and selection criteria for oilseed rape in Europe and China
identified by genome wide pedigree dissection.
AB - Selection breeding has played a key role in the improvement of seed yield and
quality in oilseed rape (Brassica napus L.). We genotyped Tapidor (European),
Ningyou7 (Chinese) and their progenitors with the Brassica 60 K Illumina Infinium
SNP array and mapped a total of 29,347 SNP markers onto the reference genome of
Darmor-bzh. Identity by descent (IBD) refers to a haplotype segment of a
chromosome inherited from a shared common ancestor. IBDs identified on the C
subgenome were larger than those on the A subgenome within both the Tapidor and
Ningyou7 pedigrees. IBD number and length were greater in the Ningyou7 pedigree
than in the Tapidor pedigree. Seventy nine QTLs for flowering time, seed quality
and root morphology traits were identified in the IBDs of Tapidor and Ningyou7.
Many more candidate genes had been selected within the Ningyou7 pedigree than
within the Tapidor pedigree. These results highlight differences in the transfer
of favorable gene clusters controlling key traits during selection breeding in
Europe and China.
PMID- 28507330
TI - Flatbed epi relief-contrast cellular monitoring system for stable cell culture.
AB - Consistent cell preparation is a fundamental preliminary step for understanding
complex cellular mechanisms in various cell-based research fields, including
basic cell biology, cancer research, and tissue engineering. However, certain
elusive factors, such as cellular de-differentiation and contamination with
mycoplasma or other types of cells, have compromised the reproducibility and
reliability of cell-based approaches. Here, we propose an epi relief-contrast
cellular monitoring system (eRC-CMS) that allows images of cells in a typical
culture plate to be acquired, stored, and analysed for daily cell quality
control. Due to its full flatbed nature and automated system, cells placed at any
location on the stage can be analysed without special attention. Using this
system, changes in the size, circularity, and proliferation of endothelial cells
in subculture were recorded. Analyses of images of ~9,930,000 individual cells
revealed that the growth activity and cell circularity in subcultures were
closely correlated with their angiogenic activity in a subsequent hydrogel assay,
demonstrating that eRC-CMS is useful for assessing cell quality in advance. We
further demonstrated that eRC-CMS was feasible for the imaging of neurite
elongation and spheroid formation. This system may provide a robust and versatile
approach for daily cell preparation to facilitate reliable and reproducible cell
based studies.
PMID- 28507331
TI - Mycoviruses of an endophytic fungus can replicate in plant cells: evolutionary
implications.
AB - So far there is no record of a specific virus able to infect both fungal and
plant hosts in nature. However, experimental evidence shows that some plant virus
RdRPs are able to perform replication in trans of genomic or DI RNAs in the yeast
Saccharomyces cerevisiae. Furthermore, tobacco mosaic virus was recently shown to
replicate in a filamentous ascomycetous fungus. Thus, at least experimentally,
some plant viruses can infect some fungi. Endophytic fungi have been reported
from many plants and several of these fungi have been shown to contain viruses.
Here we tested if mycoviruses derived from a marine plant endophyte can replicate
in plant cells. For this purpose, we used partially purified viral particles from
isolate MUT4330 of Penicillium aurantiogriseum var. viridicatum which harbors six
virus species, some having dsRNA and some positive-strand ssRNA genomes. These
were transfected into three distinct plant protoplast cell systems. Time-course
analysis of absolute RNA accumulation provided for the first time evidence that
viruses of two species belonging to the Partitiviridae and Totiviridae families,
can replicate in plant cells without evidence of host adaptation, i.e, changes in
their nucleotide sequence.
PMID- 28507333
TI - Janus monolayers of transition metal dichalcogenides.
AB - Structural symmetry-breaking plays a crucial role in determining the electronic
band structures of two-dimensional materials. Tremendous efforts have been
devoted to breaking the in-plane symmetry of graphene with electric fields on AB
stacked bilayers or stacked van der Waals heterostructures. In contrast,
transition metal dichalcogenide monolayers are semiconductors with intrinsic in
plane asymmetry, leading to direct electronic bandgaps, distinctive optical
properties and great potential in optoelectronics. Apart from their in-plane
inversion asymmetry, an additional degree of freedom allowing spin manipulation
can be induced by breaking the out-of-plane mirror symmetry with external
electric fields or, as theoretically proposed, with an asymmetric out-of-plane
structural configuration. Here, we report a synthetic strategy to grow Janus
monolayers of transition metal dichalcogenides breaking the out-of-plane
structural symmetry. In particular, based on a MoS2 monolayer, we fully replace
the top-layer S with Se atoms. We confirm the Janus structure of MoSSe directly
by means of scanning transmission electron microscopy and energy-dependent X-ray
photoelectron spectroscopy, and prove the existence of vertical dipoles by second
harmonic generation and piezoresponse force microscopy measurements.
PMID- 28507332
TI - A solid-state single-photon filter.
AB - A strong limitation of linear optical quantum computing is the probabilistic
operation of two-quantum-bit gates based on the coalescence of indistinguishable
photons. A route to deterministic operation is to exploit the single-photon
nonlinearity of an atomic transition. Through engineering of the atom-photon
interaction, phase shifters, photon filters and photon-photon gates have been
demonstrated with natural atoms. Proofs of concept have been reported with
semiconductor quantum dots, yet limited by inefficient atom-photon interfaces and
dephasing. Here, we report a highly efficient single-photon filter based on a
large optical nonlinearity at the single-photon level, in a near-optimal quantum
dot cavity interface. When probed with coherent light wavepackets, the device
shows a record nonlinearity threshold around 0.3 +/- 0.1 incident photons. We
demonstrate that 80% of the directly reflected light intensity consists of a
single-photon Fock state and that the two- and three-photon components are
strongly suppressed compared with the single-photon one.
PMID- 28507334
TI - Energy-dependent path of dissipation in nanomechanical resonators.
AB - Energy decay plays a central role in a wide range of phenomena, such as optical
emission, nuclear fission, and dissipation in quantum systems. Energy decay is
usually described as a system leaking energy irreversibly into an environmental
bath. Here, we report on energy decay measurements in nanomechanical systems
based on multilayer graphene that cannot be explained by the paradigm of a system
directly coupled to a bath. As the energy of a vibrational mode freely decays,
the rate of energy decay changes abruptly to a lower value. This finding can be
explained by a model where the measured mode hybridizes with other modes of the
resonator at high energy. Below a threshold energy, modes are decoupled,
resulting in comparatively low decay rates and giant quality factors exceeding 1
million. Our work opens up new possibilities to manipulate vibrational states,
engineer hybrid states with mechanical modes at completely different frequencies,
and to study the collective motion of this highly tunable system.
PMID- 28507336
TI - Divergent functional isoforms drive niche specialisation for nutrient acquisition
and use in rumen microbiome.
PMID- 28507335
TI - BNIP3L promotes cardiac fibrosis in cardiac fibroblasts through [Ca2+]i-TGF-beta
Smad2/3 pathway.
AB - Fibrosis is an important, structurally damaging event that occurs in pathological
cardiac remodeling, leading to cardiac dysfunction. BNIP3L is up-regulated in
pressure overload-induced heart failure and has been reported to play an
important role in cardiomyocyte apoptosis; however, its involvement in cardiac
fibroblasts (CFs) remains unknown. We prove for the first time that the
expression of BNIP3L is significantly increased in the CFs of rats undergoing
pressure overload-induced heart failure. Furthermore, this increased BNIP3L
expression was confirmed in cultured neonatal rat CFs undergoing proliferation
and extracellular matrix (ECM) protein over-expression that was induced by
norepinephrine (NE). The overexpression or suppression of BNIP3L promoted or
inhibited NE-induced proliferation and ECM expression in CFs, respectively. In
addition, [Ca2+]i, transforming growth factor beta (TGF-beta) and the nuclear
accumulation of Smad2/3 were successively increased when BNIP3L was overexpressed
and reduced when BNIP3L was inhibited. Furthermore, the down-regulation of TGF
beta by TGF-beta-siRNA attenuated the increase of BNIP3L-induced fibronectin
expression. We also demonstrated that the increase of BNIP3L in CFs was regulated
by NE-AR-PKC pathway in vitro and in vivo. These results reveal that BNIP3L is a
novel mediator of pressure overload-induced cardiac fibrosis through the [Ca2+]i
TGF-beta-Smad2/3 pathway in CFs.
PMID- 28507338
TI - Impact of Trace Minerals on Wound Healing of Footpad Dermatitis in Broilers.
AB - Footpad dermatitis (FPD) is used in the poultry industry as an animal welfare
criterion to determine stocking density. Trace minerals (TM) play a role in skin
integrity and wound healing. This study evaluated the impact of TM on FPD and
consisted of 3 treatments supplemented with 0 (NTM), low (LTM) and high (HTM) TM
levels in the same basal diet. On d21, 71% birds in all treatments developed mild
FPD and pens were top-dressed with dry litter to promote FPD healing. Compared to
NTM, LTM reduced area under the curve (AUC) of FPD lesion scores during d21-42,
HTM reduced the AUC of FPD lesion scores during d7-21 and d21-42. LTM improved
growth performance on d14, HTM improved growth performance on d14 and d28. LTM
and/or HTM increased gene expression of VEGF, TIMP3, TIMP4, MMP13, ITGA2, ITGA3
and CD40, which promoted collagen synthesis, deposition and organization; cell
migration, matrix remodeling, and angiogenesis. LTM and/or HTM increased
inflammation by upregulating TNFalpha and IL-1beta during the early wound healing
phase and reduced inflammation by downregulating IL-1beta during the late wound
healing phase. Our findings showed that TM not only improved growth performance
but also reduced FPD development by promoting FPD wound healing.
PMID- 28507337
TI - Identification and comparative analysis of the ovarian microRNAs of prolific and
non-prolific goats during the follicular phase using high-throughput sequencing.
AB - The kidding rate is one of the most important economic traits for goat
production, but the genetic mechanism that is associated with ovulation rate is
poorly understood. Recently, increasing evidence has suggested that microRNAs
(miRNAs) influence ovarian biological processes. The present study provides the
first comparison of the ovarian miRNAs of prolific Jintang black goats (JTGs) and
non-prolific Tibetan goats (TBGs) during the follicular phase using RNA-Seq
technology. We generated 11.19 million (M) and 11.34 M clean reads from the TBG
and JTG libraries, respectively, from which a total of 389 known miRNAs were
identified and 142 novel miRNAs were predicted. A total of 191 miRNAs were
differentially expressed between the two breeds. Among the 10 most abundant
miRNAs, miR-21-5p was defined as differentially expressed miRNA with a higher
level in the JTG library than in the TBG library, but the other miRNAs were not
different between the breeds. The predicted miRNA-targeted genes were further
analyzed by Gene Ontology and KEGG pathway analyses. The results revealed that
miR-21, miR-99a, miRNA-143, let-7f, miR-493 and miR-200b may affect follicular
development. These findings will increase the current understanding of the role
of ovarian miRNAs in the regulation of ovulation rate in goats.
PMID- 28507340
TI - Erratum: Stereopsis deficits in patients with schizophrenia in a Han Chinese
population.
PMID- 28507339
TI - Efficacy and tolerability of chemotherapy in Chinese patients with AIDS-related
Burkitt lymphoma and diffuse large B-cell lymphoma: An observational study.
AB - We evaluated the efficacy and tolerability of chemotherapy in HIV-infected
patients with diffuse large B-cell lymphoma (DLBCL) receiving CHOP +/- R (n = 17)
or Burkitt lymphoma (BL) receiving CODOX-M/IVAC +/- R (n = 15). The study was
conducted in Beijing Ditan Hospital from January 2009 to August 2015. The
following grade 4 adverse effects were observed in BL and DLBCL patients,
respectively: neutropenia (80% versus 47.1%), anaemia (46.7% versus 5.9%),
thrombocytopenia (53.3% versus 11.8%), bacterial pneumonia (33.3% versus 5.9%),
and sepsis (20% versus 5.9%) (p < 0.05). In the BL group, 10 (66.7%) patients
died from treatment-related or tumour-related causes, 5 (33.3%) achieved complete
response, 1 achieved partial response (6.7%), and 7 developed progressive
disease. The 1-year overall survival and progression-free survival rates were
33.3%. Of the DLBCL patients, 3 (17.6%) died from treatment-related causes, 14
(82.4%) achieved complete response, and 3 had progressive disease. The 1-year
overall survival and progression-free survival rates were 82.4%. The strongest
risk factor for death was relapse between chemotherapy cycles (adjusted hazard
ratio = 47.3; 95%CI, 4.2-528.6, p = 0.002). Initiating antiretroviral therapy
before chemotherapy failed to improve overall survival. DLBCL patients
demonstrated good responses and survival outcomes, while BL patients could not
tolerate chemotherapy due to more severe toxicity, and showed poor responses and
survival outcomes.
PMID- 28507341
TI - Increased leukotoxin production: Characterization of 100 base pairs within the
530 base pair leukotoxin promoter region of Aggregatibacter
actinomycetemcomitans.
AB - Aggregatibacter actinomycetemcomitans leukotoxin (LtxA) is a major virulence
factor that kills leukocytes permitting it's escape from host immune
surveillance. A. actinomycetemcomitans strains can produce high or low levels of
toxin. Genetic differences reside in the "so called JP2" ltxA promoter region.
These hyper-leukotoxin producing strains with the 530 bp deletion have been
studied in detail. However, regions contained within the 530 bp deletion that
could be responsible for modulation of leukotoxin production have not been
defined. Here, we report, for the first time, on regions within the 530 bp that
are responsible for high-levels of ltxA expression. We constructed a deletion of
530 bps in a primate isolate of A. actinomycetemcomitans, which produced
leukotoxin equivalent to the JP2 strain. We then constructed sequential deletions
in regions that span the 530 bps. Results indicated that expression of the ltxA
transcript was reduced by a potential transcriptional terminator in promoter
region 298 to 397 with a DeltaG = -7.9 kcal/mol. We also confirmed previous
findings that transcriptional fusion between the orfX region and ltxC increased
ltxA expression. In conclusion, we constructed a hyper-leukotoxin producing A.
actinomycetemcomitans strain and identified a terminator located in the promoter
region extending from 298-397 that alters ltxA expression.
PMID- 28507342
TI - Effects of dietary methionine on breast muscle growth, myogenic gene expression
and IGF-I signaling in fast- and slow-growing broilers.
AB - This study investigated the responses of fast- (FG) and slow- (SG) growing
broilers to dietary methionine (Met) status. The broilers were subjected to low
(LM, 0.38 and 0.28 g/100 g), adequate (AM, 0.51 and 0.42 g/100 g) and high (HM,
0.65 and 0.52 g/100 g) Met during 1-21 and 22-42 d, respectively. Compared with
the LM diets, the AM and HM diets increased body weight gain only in the FG
broilers. The HM diets increased breast muscle yield only in the FG broilers,
although insulin-like growth factor-I (IGF-I) concentration was increased in both
strains of broilers. The HM diets increased mRNA levels of myogenic regulatory
factors (MRF4, Myf5) and myocyte enhancer factor 2 (MEF2A and MEF2B) in the FG
broilers, and increased MEF2A and decreased myostatin mRNA level in the SG
broilers. Extracellular signal-regulated kinase (ERK) phosphorylation of breast
muscle was increased by the HM diets in both strains of broilers, but mechanistic
target of rapamycin (mTOR) phosphorylation was increased by the AM and HM diets
only in the FG broilers. These results reflect a strain difference in broiler
growth and underlying mechanism in response to dietary Met.
PMID- 28507344
TI - Mesporous 3C-SiC Hollow Fibers.
AB - In the present work, for the first time, we reported the exploration of
mesoporous 3C-SiC hollow fibers via single-spinneret electrospinning of
polyureasilazane (PSN) and polyvinylpyrrolidone (PVP) solution followed by high
temperature pyrolysis treatment. The resultant products were characterized by X
ray diffraction (XRD), field emission scanning electron microscopy (FESEM), high
resolution transmission electron microscopy (HRTEM) and N2 adsorption. The as
prepared hollow fibers with totally mesoporous walls were uniformly sized in
diameter and high purity in morphology. They were composed of single-crystalline
3C-SiC nanoparticles with a surface area of 21.75 m2/g and average pore diameter
of ~34 nm. The PSN concentration played a determined role on the formation of
hollow fibers rather than the conventional solid counterparts, enabling their
growth in a tunable manner. A possible mechanism was proposed for the formation
of mesoporous SiC hollow fiber.
PMID- 28507343
TI - Non-alcoholic fatty liver disease, vascular inflammation and insulin resistance
are exacerbated by TRAIL deletion in mice.
AB - Non-alcoholic fatty liver disease (NAFLD) incorporates steatosis, non-alcoholic
steato-hepatitis (NASH) and liver cirrhosis, associating with diabetes and
cardiovascular disease (CVD). TNF-related apoptosis-inducing ligand (TRAIL) is
protective of CVD. We aimed to determine whether TRAIL protects against insulin
resistance, NAFLD and vascular injury. Twelve-week high fat diet (HFD)-fed Trail
/- mice had increased plasma cholesterol, insulin and glucose compared to
wildtype. Insulin tolerance was impaired with TRAIL-deletion, with reduced p-Akt,
GLUT4 expression and glucose uptake in skeletal muscle. Hepatic triglyceride
content, inflammation and fibrosis were increased with TRAIL-deletion, with
elevated expression of genes regulating lipogenesis and gluconeogenesis.
Moreover, Trail -/- mice exhibited reduced aortic vasorelaxation, impaired
insulin signaling, and >20-fold increased mRNA expression for IL-1beta, IL-6, and
TNF-alpha. In vitro, palmitate treatment of hepatocytes increased lipid
accumulation, inflammation and fibrosis, with TRAIL mRNA significantly reduced.
TRAIL administration inhibited palmitate-induced hepatocyte lipid uptake.
Finally, patients with NASH had significantly reduced plasma TRAIL compared to
control, simple steatosis or obese individuals. These findings suggest that TRAIL
protects against insulin resistance, NAFLD and vascular inflammation. Increasing
TRAIL levels may be an attractive therapeutic strategy, to reduce features of
diabetes, as well as liver and vascular injury, so commonly observed in
individuals with NAFLD.
PMID- 28507346
TI - Eliminating wrong blood transfusions - recent advances.
PMID- 28507347
TI - Performance of TUBEX(r) TF in the diagnosis of enteric fever in private tertiary
care Hospital Peshawar, Pakistan.
AB - OBJECTIVE: To evaluate the performance of TUBEX(r) TF in diagnosing enteric
fever. METHODS: The retrospective study was performed at the Northwest General
Hospital and Research Centre, Peshawar, Pakistan, and comprised data of all
patients who had blood cultures and TUBEX(r)TF performed as part of their
evaluation from April 2011 to November 2015. SPSS 16 was used for data analysis.
RESULTS: Of the 970 patients, salmonella typhi was isolated in 43(4.43%),
paratyphi in 9(0.93%) and other organisms in 162(16.7%). TUBEX(r) TF was positive
in 18(1.86%) cases and negative in 25(2.58%). Of the culture-negative patients,
TUBEX(r) TF was positive in 35(3.6%) and negative in 136(14%). In cases where no
organism was cultured, TUBEX(r) TF was positive in 4(0.4%) and negative in
752(77.5%). The positive predictive value of TUBEX(r) TF was 31.58% and the
negative predictive value was 97.26%. The sensitivity of TUBEX(r) TF was 41.86%
while specificity was 95.97%. CONCLUSIONS: TUBEX(r) TF with its low sensitivity
and positive predictive value was a poor tool for diagnosing enteric fever.
PMID- 28507345
TI - Genetic variation and phylogeographic structure of the cotton aphid, Aphis
gossypii, based on mitochondrial DNA and microsatellite markers.
AB - Aphis gossypii, one of the most important agricultural pests in the world, can
cause serious economic losses in the main crop-producing areas. To clarify issues
such as the genetic differentiation, genetic structure, and demographic history
of A. gossypii populations, we used 10 nuclear microsatellite loci (SSR) and two
mitochondrial gene sequences (COI and Cytb) to investigate genetic diversity and
population structure of A. gossypii populations that were collected from 33
sampling sites in China from different climatic zones. SSR and mtDNA data
suggested low to moderate levels of genetic diversity. A star-shaped network of
mtDNA haplotypes indicated that the maternal ancestor of China cotton aphids
likely originated in Xinjiang. The POPTREE, STRUCTURE and principal coordinate
analysis (PCoA) revealed two genetic clusters: an eastern and a western region
group. Isolation by distance (IBD) results showed a positive correlation between
geographic distance and genetic distance in the vast eastern region but not in
the western region. Neutrality testing and mismatch distribution analysis
provided strong evidence for a recent rapid expansion in most populations.
Genetic bottleneck was not detected in A. gossypii populations of China. The
present work can help us to develop strategies for managing this pest.
PMID- 28507348
TI - Microbiological pattern of diabetic foot infections at a tertiary care center in
a developing country.
AB - OBJECTIVE: To determine the microbiological profile and antibiotic susceptibility
patterns of organisms isolated from diabetic foot ulcers in a tertiary care
hospital Karachi, Pakistan. METHODS: This descriptive study was conducted at the
Baqai Institute of Diabetology and Endocrinology (BIDE), from January 2013 to
March 2014. Bone, pus and tissue samples were collected from 342 patients with
diabetic foot infections and inoculated on appropriate media. Antibiotic
susceptibility tests were done by Kirby Bauer disk diffusion method. RESULTS: A
total of 671 aerobic bacteria were isolated from 473 specimens with an average of
1.45 isolates per specimen. Poly-microbial infection was 56.87%. Gram- negative
isolates were predominant 76.27%.Staphylococcus aureus was most frequent among
Gram-positive 20.7% and Escherichia coli 15.72% in Gram negative isolates. MRSA
was found in 26.76% Staphylococcus aureus. About 33.48% of antimicrobial
resistant isolates were observed. CONCLUSIONS: In our study, Gram negative
aerobes were predominant in the diabetic foot infections. A significant number of
MDR isolates were also observed in this cohort. Delayed referral and
inappropriate use of broad spectrum antibiotics may be the main cause of increase
in the frequency of MDR isolates.
PMID- 28507349
TI - Antibiotics in acute calculous cholecystitis - do Tokyo guidelines influence the
surgeons' practices?
AB - OBJECTIVE: To observe changes in surgeons' practice of antibiotic usage in
patients with acute cholecystitis before and after the implementation of Tokyo
Guidelines. METHODS: This retrospective, descriptive study was conducted at the
Aga Khan University Hospital, Karachi, and comprised the medical records of all
patients with the diagnosis of acute calculus cholecystitis who presented in 2009
and those who presented in 2014 after the implementation of Tokyo Guidelines. The
major variables included patients' demographics, antibiotics used and surgical
outcomes. SPSS 19 was used for data analysis. RESULTS: Of the 356 patients,
96(27%) were treated in 2009 and 260(73%) in 2014. The overall mean age was
48.9+/-14 years. There were 185(52%) females and 171(48%) males. Comparison of
the data from 2 years showed no difference in gender, American Society of
Anaesthesiologists level, grade of acute cholecystitis and frequency of use of
empiric antibiotics (p>0.05 each). However, there was significantly less use of
combination therapy (p=0.00) and metronidazole (p=0.00) in 2014than in 2009.
Interval cholecystectomy was significantly less practised in 2014 (p=0.03)
resulting in shorter hospital stay (p=0.00). Despite improvement in antibiotic
usage practices, post-operative infection rates remained the same in both the
groups (p=0.58). CONCLUSIONS: Implementation of Tokyo Guidelines not only greatly
influenced but also standardised the choice of antibiotics in patients without
compromising the infective and surgical outcomes.
PMID- 28507350
TI - Amplification of Mitochondrial DNA for detection of Plasmodiumvivax in
Balochistan.
AB - OBJECTIVE: To access a new step using PCR to amplify the targeted mtDNA sequence
for detecting specifically Plasmodium vivax and its co-infections, false positive
and false negative results with Plasmodium falciparum. METHODS: In this study we
have standardized a new technical approach in which the target mitochondrial DNA
sequence (mtDNA) was amplified by using a PCR technique as a tool to detect
Plasmodium spp. Species specific primers were designed to hybridize with
cytochrome c oxidase gene of P. vivax (cox I) and P. falciparum (cox III). Two
hundred blood samples were collected on the basis of clinical symptoms which were
initially examined through microscopic analysis after preparing Giemsa stained
thick and thin blood smears. Afterwards genomic DNA was extracted from all
samples and was then subjected to PCR amplification by using species specific
primers and amplified segments were sequenced for confirmation of results.
RESULTS: One-hundred and thirty-two blood samples were detected as positive for
malaria by PCR, out of which 64 were found to be positive by PCR and 53 by both
microscopy and PCR for P.vivax infection. Nine samples were found to be false
negative, one P.vivax mono infection was declared as co infection by PCR and 3
samples identified as having P.falciparum gametes were confirmed as P.vivax by
PCR amplification. Sensitivity and specificity were found to be 85% and 92%
respectively. CONCLUSIONS: Results obtained through PCR method were comparatively
better and reliable than microscopy.
PMID- 28507351
TI - Practice of breastfeeding and Immunisation in a periurban community in Pakistan.
AB - OBJECTIVE: To assess the practice of breastfeeding and immunisation in a peri
urban community and correlate it with maternal care during pregnancy of the index
child. METHODS: This community-based, cross-sectional survey was conducted at
Shifa Tameer-e-Millat University and Shifa College of Medicine, Islamabad,
Pakistan, from June 2014 to January 2016, using a self-generated questionnaire.
Systemic random sampling method was used to collect data. SPSS 21 was used to
analyse the data and to find associations between maternal care and practices of
breastfeeding. RESULTS: There were 1,275 participants in the study. The mean age
of the participants was 31.61+/-8.026 years and the mean number of family members
was 7.28+/-3.42. Overall, 1,121(87.9%) women had exclusively breastfed all their
children while 906(71.1%) women had their children fully vaccinated. The mean
duration of exclusive breastfeeding was 5.30+/-1.31 months while the mean
duration of mixed breastfeeding was 16.70+/-8.62 months. Mothers who were given
prenatal care were 2.60 and 2.91 times more likely to do exclusive breastfeeding
and immunisation, respectively, compared to women who were not given prenatal
care (p<0.05). CONCLUSIONS: There is a dire need to focus more on routine
services compared to massive immunisation and breastfeeding campaigns.
PMID- 28507352
TI - Candidiasis: Prevalence and resistance profiling in a tertiary care hospital of
Pakistan.
AB - OBJECTIVE: To determine Candida colonisation/infection in renal transplant
patients and to determine the resistance pattern against antifungal drugs.
METHODS: This prospective, observational study was conducted at Al-Sayyed
Hospital, Rawalpindi, Pakistan, from January to October 2014, in collaboration
with the Microbiology and Public Health Laboratory's, Islamabad campus..The
clinical specimens investigated included respiratory tract secretions, blood,
urine, high vaginal swab, skin scrapings, and plastic devices samples. RESULTS:
Of the 7,850 samples, 164(2.08%) were positive for Candida. Candida albicans were
most prevalent as they were found in 114(69%) samples. Besides, 56(34%) of the
positive samples were resistant to one or more antifungal agents. Highest
resistance was obtained against fluconazole. We found only 5(3.04%) positive
samples of Candida glabrata; of them, 3(60%)were resistant. In case of Candida
spp, 27(48%) resistance was observed. In Candida albicans, 23(41%) of the samples
were found to be resistant. Most of the Candida isolates was recovered from
bronchial alveolar lavage. CONCLUSIONS: Although Candida albicans remained the
main responsible species for Candida infections, but non-albican Candida species
are also emerging.
PMID- 28507353
TI - Comparison of ketamine-propofol and ketamine-dexmedetomidine combinations in
children for sedation during tooth extraction.
AB - OBJECTIVE: To evaluate the efficiency of ketamine-propofol and ketamine
dexmedetomidine drugs in children for sedation during tooth extraction. METHODS:
The randomised, prospective study was conducted at the Department of Oral and
Maxillofacial Surgery, Faculty of Dentistry, Erciyes University, Kayseri, Turkey,
from September to November 2013, and comprised children who were due to undergo
tooth extraction. Non-invasive blood pressures (systolic and diastolic),
peripheral oxygen saturation, heart and respiratory rates and Ramsay Sedation
Scores were assessed at baseline, after applying the drugs and then every 5
minutes thereafter. Further, the ketamine-propofol group received 1mg kg-1 of
ketamine and propofol, and the ketamine-dexmedetomidine group received 1mg kg-1
of ketamine + 0.5 ug kg1 of dexmedetomidine. RESULTS: Of the 60 participants,
there were 30 (50%) in each group. No statistically significant differences were
found in terms of heart rate, non-invasive blood pressures at any time and the
number of drug repetitions (p>0.05). Nausea-vomiting was statistically higher in
the ketamine-dexmedetomidine group (p<0.05). CONCLUSIONS: Ketamine-propofol might
be a better option due to lower vomiting and nausea episodes and higher surgeon
satisfaction levels.
PMID- 28507354
TI - The bilobed flap - a better option for soft tissue release in the management of
Radial Club Hand.
AB - OBJECTIVE: To establish that the bilobed flap as soft tissue release component
for the radial club hand is superior to the z-plasty technique in type III and IV
radial club hands. METHODS: This study was conducted at the Shifa International
Hospital, Islamabad, Pakistan, from 2009 to 2015, and comprised patients with
radial club hands operated by a single consultant plastic surgeon. Soft tissue
release was performed at 08 months. The extremity was then casted for 08 weeks
and kept in a long-arm cast for 3 to 6 months. RESULTS: Twelve radial club hands
of 9 patients treated successfully during the study period showed good to
excellent results. Z-plasty was used on the radial side to correct the soft
tissue deficiency in 5(42%) hands, and a bilobed flap in 7(58%) hands for soft
tissue rearrangement on the radial side. Of all hands, 1(8.3%) z-plasty flap
developed partial flap necrosis and 1(8.3%) each developed infection and needed
implant (Kirschner wire removal), which were dealt with efficiently with no long
term sequelae. CONCLUSIONS: The bilobed flap was found to be superior to the z
plastytechnique since the flap had better predictability and no tissue was
wasted.
PMID- 28507355
TI - Estimation of uncertainty measurement - A prerequisite of ISO1589 accreditation
for clinical laboratories.
AB - OBJECTIVE: To estimate relative expanded uncertainty measurement of routine
clinical chemistry analytes for international organisation for standardisation
15189 accreditation. METHODS: This cross-sectional study was conducted at Dow
International Medical College, Karachi, from September 2013 to May 2014. During
the process of international organisation for standardisation 15189
accreditation, measurement uncertainty was estimated for 13 clinical chemistry
analytes using top-down approach. Relative combined uncertainty of each analyte
was calculated by combining uncertainties of imprecision, bias and calibrators.
Results of estimated imprecision, bias and expanded uncertainties were observed
for allowable imprecision, bias and total analytical error for the respective
analyte.. RESULTS: Uncertainties of imprecision were found within acceptable
limits for all analytes except total protein (2.4% vs. 1.3%). Uncertainties of
bias of all analytes were found within allowable limits. Relative expended
uncertainties of all analytes were found acceptable except total protein (4.7%vs
3.63%). CONCLUSIONS: The approach used to estimate the measurement uncertainty
may be found simple and feasible by clinical laboratories interested in getting
the relevant accreditation.
PMID- 28507356
TI - School going adolescents' perception of family climate and mental problems:
Results from Kocaeli, Turkey.
AB - OBJECTIVE: To investigate the association between the perception of expressed
emotion and psychopathology of school-going adolescents in a non-clinical sample.
METHODS: The cross-sectional field study was conducted in Kocaeli, Turkey, and
comprised high-school students during the 2014-15 school years. Data was
collected using the Information Collection Form, Strengths and Difficulties
Questionnaire and Shortened Level of Expressed Emotion Scale. SPSS 21 was used
for data analysis. RESULTS: Of the 487 subjects, 295(60.57%) were girls and
192(39.43%) were boys. The overall median age was 16 (inter-quartile range: 15-17
years). There were significant positive relationships between the scales in terms
of emotional problems (p<0.001), behavioural problems (p<0.001), Attention
deficit/hyperactivity disorder (p<0.001), and peer relationship problems
(p<0.001). There was also a negative significant relationship between pro-social
behaviours and expressed emotion (p<0.001). CONCLUSIONS: The concept of perceived
expressed emotion in non-clinical adolescents is useful in alarming clinicians
and preventing mental disorders.
PMID- 28507357
TI - Effect of skill laboratory training on academic performance of medical students.
AB - OBJECTIVE: To observe the effect of skill lab training on academic performance of
final year medical students in terms of marks obtained in long case, short case,
objective structured clinical examination and viva. METHODS: The cross-sectional
comparative study was conducted at Army Medical College, Rawalpindi from February
to April 2015. Two batches of final year MBBS were recruited for the study. Batch
1 received conventional training, and Batch 2 received skill lab training. The
performance of students was assessed by comparing the marks obtained in long
case, short case, objective structured clinical examination and viva. Data was
analysed using SPSS 23. RESULTS: Of the 335 subjects, 168(50.1%) were male and
167(49.9%) were female students with a mean age of 21.79+/-1.02 years. Batch 1
had 151(45%) students and Batch 2 had 184(55%). Batch 2 got significantly higher
marks in long case, short case and objective structured clinical examination
(p<0.05 each). Viva result was not found to be related to training (p>0.05).
CONCLUSIONS: Acquisition of clinical skills significantly improved when medial
students were trained in skill laboratories.
PMID- 28507358
TI - Effect of Citrullus colocynthis aqueous seed extract on beta cell regeneration
and intra-islet vasculature in alloxan induced diabetic male albino rats.
AB - OBJECTIVE: To observe the effect of Citrullus colocynthis on beta cell
regeneration and intra-islet vasculature. METHODS: This experimental study was
conducted at the University of Health Sciences, Lahore, Pakistan, from February
2013 to January 2014. It comprised male wistar rats weighing 100-150gand aged 6-8
weeks. The animals were divided into 6 groups. Group A1 served as control.
Diabetes was induced in groups A2, B2 and C2 using single intravenous injection
of 50mg/kg of alloxan. Animals having fasting blood glucose>250mg/dl were
considered diabetic. Diabetic rats in groups B2 and C2 and their controls B1 and
C1 were given 1ml/kg and 2ml/kg of Citrullus colocynthis aqueous seed extract
orally per day for 14 days. Animals were sacrifised on day 15. RESULTS: Of the 48
rats, there were 8(16.7%) in each group. Citrullus colocynthis has stabilized the
body weight of rats and difference was statistically significant on days
7(p<0.013) and 14(p<0.001). Citrullus colocynthis significantly reduced (p<0.001)
the fasting blood sugar levels in a dose- and time-dependent manner. It increased
the islet diameter (p<0.001) and beta cell count (p<0.001). The number of intra
islet capillaries was increased in group C2, but the difference was not
statistically significant (p>0.05). CONCLUSIONS: Citrullus colocynthis aqueous
seed extract stabilised animal body weight and ameliorated hyperglycaemia in a
dose- and time-dependent manner which was attributable to regenerative effect on
beta cells and intra-islet vasculature.
PMID- 28507359
TI - Under-representation of women in the editorial boards of medical and dental
journals of Pakistan.
AB - OBJECTIVE: To explore the representation of females in the field of medical
journal editing in Pakistan. METHODS: This cross-sectional study was conducted
from July 3 to 15, 2015 at Combined Military Hospital, Lahore. After exploring
the website of Pakistan Medical and Dental Council, we surveyed the website of
each journal and from their latest available edition discerned the editorial
board's gender composition. Designations of female members were noted. Data was
analysed using SPSS 20. RESULTS: A total of 2342 members served on the editorial
boards of 79 journals of which 410(17.51%) were females. The maximum strength of
women in a single journal was 23/30(76.6%). There were no women in the editorial
boards of 11 (13.92%) journals. Among others, there were 188 (45.9%) Members of
Editorial Board, 39 (9.5%) Editors, 39 (9.5%) Associate Editors, 34 (8.3 %)
Members Advisory Board, 22 (5.4%) Subject Editors, 10 (2.4%) Editors-in-chief, 8
(2.0%) Student Editors, 7 (1.7%) Statisticians, 3 (0.7%) Bibliographers, 2 (0.5%)
Deputy Editors-in-chief, 1 (0.2%) Trainee Editor and 1(0.2%) epidemiologist.
CONCLUSIONS: There was a low representation of women in the field of journal
editing. A number of factors may be incriminated for this poor visibility.
PMID- 28507360
TI - Psychometric properties of Conversion Disorder Scale- Revised (CDS) for children.
AB - OBJECTIVE: To revise conversion disorder scale and to establish the psychometric
properties of the revised scale. METHODS: This case-control study was conducted
from February to June, 2014, at the Government College University, Lahore,
Pakistan, and comprised schoolchildren and children with conversion disorder. In
order to generate items for revised version of conversion disorder scale, seven
practising mental health professionals were consulted. A list of 42 items was
finalised for expert ratings. After empirical validation, a scale of 40 items was
administered on the participants and factor analysis was conducted. RESULTS: Of
the240 participants, 120(50%) were schoolchildren (controls group) and
120(50%)were children with conversion disorder (clinical group).The results of
factor analysis revealed five factors (swallowing and speech symptoms, motor
symptoms, sensory symptoms, weakness and fatigue, and mixed symptoms) and
retention of all 40 items of revised version of conversion disorder scale.
Concurrent validity of the revised scale was found to be 0.81 which was
significantly high. Similarly, discriminant validity of the scale was also high
as both clinical and control groups had significant difference (p<0.001) in
scores. Cronbach's alpha of scale was a=0.91 while item total correlation ranged
from 0.50 to 0.80. The sensitivity and specificity analysis indicated that the
revised conversion disorder scale was 76% sensitive to predicting conversion
disorder while specificity showed that the scale was 73% accurate in specifying
participants of the control group. CONCLUSIONS: The revised version of conversion
disorder scale was a reliable and valid tool to be used for screening of children
with conversion disorder.
PMID- 28507361
TI - Self-related factors and decision making styles among early adults.
AB - OBJECTIVE: To examine the effect of self-related factors, including self
regulation, self-esteem and self-efficacy, on decision-making styles of early
adults. METHODS: The cross-sectional study was conducted from February to August,
2014 at four universities of Islamabad, Pakistan, and comprised adult students of
both Social and Natural sciences. Data was collected through Self-Regulation
Questionnaire, Self-Esteem Scale, Self-Efficacy Scale and the General Decision
Making Styles Questionnaire. Data was subjected to multivariate regression
analysis. RESULTS: Of the 300 participants, 160(53%) were men and 140(47%) were
women. The overall mean age was 22.68+/-5.96 years. Besides, 170(56%) were
studying Social sciences and 130(44%) Natural sciences. Self-regulation, self
esteem and self-efficacy positively predicted rational and intuitive style and
negatively predicted avoidant and spontaneous style. Self-efficacy and self
regulation negatively predicted dependent style. CONCLUSIONS: Ensuring positive
self-related factors affected adults' effective decision-making choices.
PMID- 28507362
TI - Visual outcome of retinal vein occlusion in patients residing at high altitude.
AB - OBJECTIVE: To study visual outcome in patients of high altitude retinopathy
presenting with retinal venous occlusion. METHODS: The randomised clinical trial
study was conducted at the Armed Forces Institute of Ophthalmology, Rawalpindi,
Pakistan, from January 2013 to December 2015, and comprised eyes of lowlanders.
Patients staying at high altitude (>8,000 feet above sea level) as part of their
service duty and presented with retinal venous occlusive disease were included.
Patients with history of diabetes, hypertension, glaucoma, any pre-existing
retinal disease or age-related conditions responsible for decreased vision were
excluded. Detailed ocular as well as systemic examination was carried out to
establish the diagnosis of retinal venous occlusion. Patients were divided into
two groups. First group was observed over a period of 6 months and labelled as
control group, whereas the second group was treated with intravitrealbevacizumab
and labelled as intervention group. Complete ocular examination was carried out
in all patients at 4 weeks, 3 months and 6 months. SPSS 21 was used for data
analysis. Results: A series of 32 eyes of 28 male patients were included. The
overall mean age was 31.40+/-3.40 years. The mean altitude of their temporary
stay was 4,120+/-941 metres above sea level and the mean duration of stay was
6.80+/-4.13months. Besides, 21(75%) subjects were smokers. Moreover, 26(81.25%)
eyes had central retinal vein occlusion while branch retinal vein occlusion was
seen in 6(18.75%) eyes. The mean visual acuity in the control group was 0.70+/
0.56 on Logarithm of the Minimum Angle of Resolution chart at the presentation
while it was 0.26+/-0.87, 0.20+/-0.32 and 0.15+/-0.23 after 4 weeks, 3 months and
6 months, respectively. The mean best corrected visual acuity in intervention
group was 0.68 +/- 0.46 before treatment and 0.15+/-0.11, 0.12+/-0.11 and 0.10+/
0.08 at 4 weeks, 3 months and 6 months, respectively. Significant post
intervention change was observed in best corrected visual acuity at 6 months
(p<0.05) in patients who presented with severe visual loss. CONCLUSIONS:
Treatment with intravitrealbevacizumab may be considered in patients with severe
visual loss at presentation.
PMID- 28507364
TI - Evaluation of a communication skills training course for medical students using
peer role-play.
AB - OBJECTIVE: To evaluate the effect of using peer role-playing in learning the
communication skills as a step in the development of the communication skills
training course delivered to pre-clinical medical students. METHODS: This study
was conducted at the King Abdulaziz University, Jeddah, Saudi Arabia, between
September 2014 and February 2015 and comprised medical students. Mixed methods
design was used to evaluate the developed communication skills training course.
Tests were conducted before and after the communication skills training course to
assess the students' self-reported communication. After the course, the students
completed a satisfaction survey. Focus groups were conducted to assess the
behavioural and organisational changes induced by the course. SPSS 16 was used
for data analysis.. RESULTS: Of the293 respondents, 246(84%) were satisfied with
the course. Overall, 169(58%) subjects chose the lectures as the most helpful
methods for learning the communication skills while 124(42%) considered practical
sessions as the most helpful method. Besides, 237(81%) respondents reported that
the role-play was beneficial for their learning, while 219(75%) perceived the
video-taped role-play as an appropriate method for assessing the communication
skills. CONCLUSIONS: Peer role-play was found to be a feasible and well-perceived
alternative method in facilitating the acquisition of communication skills..
PMID- 28507363
TI - Status of cold chain in routine immunisation centres of the Expanded Programme on
Immunisation in Quetta, Pakistan.
AB - OBJECTIVE: To determine the status of cold chain and knowledge and practices of
health workers about cold chain maintenance in routine immunisation health
centres. METHODS: This cross-sectional study was conducted in Quetta, Pakistan,
from May to July 2012, and comprised health facilities in the district. We
interviewed the staff responsible for vaccine storage and cold chain maintenance
and used a checklist to assess cold chain maintenance of routine expanded
programme on immunisation vaccines. SPSS 16 was used for data analysis.. RESULTS:
Of the 42 health facilities, staff of 13(30%) wrongly indicated that measles and
Bacillus Calmette-Guerin were cold sensitive vaccines. Temperature of the ice
lined refrigerators was not maintained twice daily in 18(43%) centres. There were
no voltage stabilisers and standby power generators in 31(74%) and 38(90%)
centres, respectively. Vaccine arrangement was found to be inappropriate in ice
lined refrigerators of 38(90%) centres and ice packs were incorrectly used in
carriers in 22(52%) centres. Vaccine stock was not charted in 39(93%) centres.
Moreover, 4(10%) facilities did not have dedicated expanded programme on
immunisation rooms whereas about 5(12%) and 33(79%) had no vaccinator and
separate expanded programme on immunisation incharge appointed. Also, 32(76%)
centres did not have a female vaccinator appointed. CONCLUSIONS: Although the
majority of health staff had adequate knowledge, there were weaknesses in
practice of maintaining the cold chain.
PMID- 28507365
TI - Frequency and predictors of metabolic syndrome in adolescents /first year medical
students of a public sector medical college Quetta, Pakistan.
AB - Objective: To determine the prevalence of metabolic syndrome in medical students.
METHODS: This cross-sectional study was conducted at the Bolan Medical College,
Quetta, Pakistan, from August 2015 to January 2016, and comprised healthy first
year medical students. Demographic data was assessed using a self-administered
questionnaire. Height, weight and waist circumference were measured along with
fasting blood sugar, high-density lipoprotein and triglycerides by using
automated biochemistry analyser. SPSS 20 was used for data analysis. RESULTS: Of
the 225 participants, 127(56.4%) were females. The overall mean age was 18.80+/
0.426 years. Frequency of metabolic syndrome was 32(14.2%). Increased waist
circumference, fasting blood sugar and triglycerides were associated with an
increased likelihood of exhibiting metabolic syndrome (p<0,05 each). Male gender
and high-density lipoprotein were found to be protective against metabolic
syndrome (p<0.05 each).. CONCLUSIONS: The prevalence of metabolic syndrome is
increasing in our adolescent population which demands screening from childhood
and early adolescence..
PMID- 28507366
TI - Over a decade of changing trends in surgical mortality; audit from a tertiary
care hospital.
AB - OBJECTIVE: A retrospective audit of the trend of mortality in the general surgery
service at our hospital over the last decade was conducted to reflect the
complexity of cases being seen. METHODS: Mortalities of 8 separate years, a
decade apart, namely 1997, 1998, 1999, and 2000 as initial years (Group-I) and
2011, 2012, 2013 and 2014 as recent years (Group-II) were reviewed. RESULTS:
Total number of admissions in the service and surgeries performed during these
two periods experienced an increase of 50.7% & 64.2 % respectively. The total
mortalities showed an increase with 139 (mortality rate 0.96%) seen in Group I to
285 (mortality rate 1.31%) seen in Group II a percentage increase of 105%.
Comparing the operative mortality, separately, mortality rate dropped from 1.21%
to 1.16% of all surgeries. Analyzing non-operative mortality showed a significant
increase from six deaths in Group-I comprising 4.3% to 76 non-operative deaths in
Group-II corresponding to 26.7% (p=0.000). Deaths due to Trauma increased from
12.9% to 25.3%, p=0.04, a reversed trend was seen in deaths due to GI Bleeding
11.5% to 3.2%, p=0.001. Significantly more patients in Group-II had higher ASA
levels as compared to Group-I (62% vs. 46%, p<0.005). CONCLUSIONS: This study
shows an increase in total mortality rate over the years, change was mainly due
to an increase in non-operative mortality. Trauma became the predominant cause of
death.
PMID- 28507367
TI - Management of cervical trauma: A Brief review.
AB - Cervical injury is not uncommon in any trauma, especially in road traffic
accident. A standard approach, towards, transport, workup, and management is
required for best outcomes, and decrease morbidity. We tried to review the recent
literature and briefly discuss the management protocols concluded that in our
setting, emergency ambulance personnel and Emergency Room doctors should be
trained in dealing with all kinds of cervical spine trauma, they should be aware
of recent guidelines and should refrain from using steroids routinely. By
following guidelines, large numbers of cervical spine injury patients can
benefit.
PMID- 28507368
TI - The confounding factors leading to plagiarism in academic writing and some
suggested remedies: A systematic review.
AB - There is a staggering upsurge in the incidence of plagiarism of scientific
literature. Literature shows divergent views about the factors that make
plagiarism reprehensible. This review explores the causes and remedies for the
perennial academic problem of plagiarism. Data sources were searched for full
text English language articles published from 2000 to 2015. Data selection was
done using medical subject headline (MeSH) terms plagiarism, unethical writing,
academic theft, retraction, medical field, and plagiarism detection software.
Data extraction was undertaken by selecting titles from retrieved references and
data synthesis identified key factors leading to plagiarism such as unawareness
of research ethics, poor writing skills and pressure or publish mantra.
Plagiarism can be managed by a balance among its prevention, detection by
plagiarism detection software, and institutional sanctions against proven
plagiarists. Educating researchers about ethical principles of academic writing
and institutional support in training writers about academic integrity and
ethical publications can curtail plagiarism.
PMID- 28507369
TI - Nature, scope and use of economic evaluation of healthcare programmes: with
special reference to Pakistan.
AB - Economic evaluation (EE)/cost effectiveness analysis(CEA) of healthcare
programmes is an emerging area, yet the resource base to apprehend EE/CEA is very
limited in Pakistan. This paper attempts to fill this gap by providing a basic
text in the field of EE with special reference to Pakistan. We used four
dimensional criteria (available, relevant, complete and accurate) for reviewing
the EE contents in the locally available textbooks and reading material on public
health. We find CEA as core competency and skill of medical doctors in
undergraduate medical curricula yet we could not find EE contents in the
recommended textbooks. We find that economic evaluation entails two rules: both
cost and effectiveness should be included in the analysis, and there must be a
comparison of at least two drugs or medical intervention. We describe EE/CEA in
this article and recommend that EE content should be included in the medical and
public health curriculum in Pakistan.
PMID- 28507370
TI - A comparative study of dynamic soft tissue mobilization vs. passive stretching
technique to improve the flexibility of hamstrings in cricket players.
AB - Different therapies are available for correcting the tightness of hamstring
muscles. Objective of this study was to compare the effectiveness of Dynamic Soft
Tissue Mobilization DSTM technique and Passive Stretching PS to improve the
flexibility of tight hamstrings in cricket players. A total of 120 cricket
players having tightness of hamstrings were enrolled and randomized into two
groups A and B using lottery method. Group-A was treated with DSTM and group-B
with PS to improve the flexibility of hamstrings. Active Knee Extension Angle
AKEA test was used to measure the hamstring tightness as it is a gold standard
test for this purpose. The mean value of AKEA, pre-treatment score deficient to
180 degrees for DSTM was 25.66 +/- 6.90, and that of PS was 25.46 +/- 6.89, while
the post-treatment score was 10.81 +/- 4.30, and 18.63 +/- 7.06 respectively.
Post-treatment score for DSTM was statistically lower than PS. (p-value < 0.05).
So it was concluded that it is better to use DSTM for acquiring better results.
PMID- 28507371
TI - Intellectual wellness in medical university teachers: Gender based comparison.
AB - A cross section, questionnaire based study was carried out from January 2012 till
December 2014 to compare intellectual wellness (IW) awareness on the basis of
gender in teachers of basic sciences at medical universities of Karachi,
Pakistan. Data was collected from 3 public and 5 private medical universities of
Karachi, Pakistan. Questionnaire was tailored from "Wellness Wheel" and responses
were aggregated for eight questions in the dimension of IW to obtain aggregate IW
score. Reliability of the questionnaire was measured using Cronbach's alpha. The
average intellectual score was 24.99 +/- 3.93 with a minimum score of 8 and
maximum 32.The frequency of keeping informed about research updates was
significantly higher in males (p = 0.043) that emphasized significantly better IW
awareness of male medical teachers involved in teaching of medical sciences in
both public and private medical universities of Pakistan.
PMID- 28507372
TI - Medicinal role of papaya seeds on thrombocyte count tested on healthy rabbits.
AB - The main objective of the current study is to evaluate the medicinal role of
Papaya seeds on thrombocyte count and hepatic parameter on healthy rabbits.
Experimental and Interventional study, at the Department of pharmacology Baqai
Medical University Karachi. Rabbits (18 in number different age and both sex)
were included, subsequently subdivided into three group (n=6). Group A (Control),
B and C (sample fed dose 250 & 500mg OD, oral route). Blood were drawn 0 time,
subsequently samples were drawn at 15, 30, 45 days. Data was analyzed by using
SPSS 19.0. Analysis of results showed increase in the Platelet level 19.2%,
65.5%. No significant change seen in the SGPT, Alkaline Phosphatase, WBC,
Neutrophil, Lymphocytes, Eosinophils and Monocytes as compared with the controls.
It can be concluded that the administration of Papaya seeds powder dose rapidly
increase platelet count and may play an important therapeutic role in
thrombocytopenia.
PMID- 28507373
TI - Comparison of low level laser therapy and interferential current on post stroke
shoulder pain.
AB - The objective of the study was to compare the effects of LASER therapy and
Interferential current on post stroke shoulder pain. Diagnosed patients (n=38) of
post stroke shoulder pain were randomly divided into two groups i.e., LASER group
(LG =20 patients) and Interferential current group (IFCG=18 patients). The
variables under study were pain, satisfaction, disability, and function level
before and after treatment. Improvement in pain and satisfaction level after
LASER therapy was significant (p<0.001). However improvement in functional level
was not significant (p> 0.05). The study findings revealed that LASER therapy is
more effective than Interferential current in decreasing pain and increasing
satisfaction level of stroke patients having shoulder pain.
PMID- 28507375
TI - Twin abdominal pregnancy - A rare scenario.
AB - Twin abdominal pregnancy is rarely encountered by gynaecologists throughout their
professional career. It poses a challenge in terms of diagnosis and management.
This case report is about a patient who was diagnosed and successfully managed
for this complication at a peripheral hospital of Pakistan Armed Forces.
PMID- 28507374
TI - Ophthalmo-genetic analysis of Pakistani patients with nonsyndromic oculocutaneous
albinism through whole exome sequencing.
AB - Oculocutaneous albinism (OCA) is a disorder of defective melanin biosynthesis
that is characterized by hypo-pigmentation of skin, hair and retinal pigment
epithelium. Phenotypically, OCA patients exhibit white milky skin, whitish to
golden hair and deterioration of retinal cells. Until recently, genetic studies
have reported seven causative genes (TYR, TYRP1, OCA2, SLC45A2, SLC24A2, C10ORF11
and MCIR) and an uncharacterized OCA5 locus. Herein we present the medico-genetic
study of three Pakistani patients inheriting autosomal recessive OCA. Whole exome
sequencing, followed by Sanger DNA sequencing for segregation analysis, revealed
recurrent mutations c.346C>T (p.Arg116*) and c.1255G>A (p.Gly419Arg) (family A
and B respectively) in TYR gene, while the patient from family C did not reveal
any known gene mutation, which suggests the involvement of some novel genetic
factor. It is the first report of mapping c.346C>T mutation in a Pakistani
patient. Our study further extends the evidence of genetic hotspots regions in
TYR gene causing OCA in Pakistani population.
PMID- 28507376
TI - Extraoral approach of the surgical treatment of sublingual epidermoid cyst: A
case report.
AB - Epidermoid and dermoid cysts account for <0.01% of all oral cavity lesions with
dermoid cyst which is twice as common to epidermoid. Epidermoid cysts are benign
lesions that occur rarely in children. They usually present early in life as an
asymptomatic mass. The treatment option is surgical and intraoral or extraoral
approaches can be performed according to the localization and size of the mass.
This report presents an 11 year old child with a sublingual epidermoid cyst
treated extraorally.
PMID- 28507377
TI - Spontaneous evisceration of umbilical hernia in a patient with congenital
nephrotic syndrome.
AB - Congenital nephrotic syndrome is a term used to describe a condition in babies
who develop severe proteinuria and hypoalbuminaemia within their first three
months of life. They generally have oedema and ascites from birth which, because
of increased intra-abdominal pressure, can result in an umbilical hernia. The
report presents a five-month old infant with congenital nephrotic syndrome who
had spontaneous umbilical hernia rupture with evisceration. The approach to
umbilical hernias is usually conservative, but in selected cases elective surgery
may be indicated.
PMID- 28507378
TI - Case series of rare Interstitial Lung Disease (ILD).
AB - Pulmonary alveolar proteinosis (PAP) is a rare lung disease where periodic acid
Schiff (PAS)-positive eosinophilic material accumulates in the alveoli of the
lungs. Here we describe two cases of young males who presented with dynpnoea and
weight loss. The HRCT scan of the chest in both cases showed the typical "crazy
paving" pattern and lung biopsies confirmed the diagnosis of PAP. They showed
remarkable symptomatic improvement with therapeutic whole lung lavage.
PMID- 28507379
TI - Accuracy of frozen sections in oral cancer resections, an experience of a
tertiary care hospital.
AB - The aim our study was to determine the accuracy of frozen sections in oral cancer
resections. Patients who underwent oral cancer resection at Patel Hospital were
included in the study. Tissues for frozen sections were obtained from the mucosal
margins and tumour bed. Frozen sections were compared with the paraffin embedded
sections which served as the gold standard in our study. Sensitivity,
specificity, positive predictive value, negative predictive value, accuracy and
kappa statistics were calculated. A total of 299 frozen sections were obtained
from 77 patients who underwent oral cancer resection, mean (3.88+/-0.76). Frozen
sections' sensitivity in relation to permanent sections was 72.7% and specificity
of 93.9%. The overall accuracy of the test was 90.9%. Kappa value was calculated
to be 0.642, which showed a moderate agreement. Frozen sections are accurate
enough to be used in assessing intraoperative margin assessment for tumour
clearance.
PMID- 28507380
TI - Malaria and diabetes.
AB - Both malaria and diabetes are more common in the developing world, and are major
public health challenges. A direct relationship between these 2 conditions has
not been evaluated. This review article assessed the literature guaging the
relationship between these two conditions, and suggests a pragmatic approach to
management. References for this review were identified through searches of
PubMed, Medline, and Embase for articles published to October 2016 using the
terms "diabetes" [MeSH Terms] AND "malaria" [All Fields]. The reference lists of
the articles thus identified were also searched. The search was not restricted to
English-language literature. Malaria has been documented to be more common in
diabetes, in several studies from Africa. Malarial infection during pregnancy is
an important cause of low birth weight and anaemia, and may contribute to the
intra-uterine hypothesis explanation for the diabetes epidemic. Prevention and
timely/effective management of malaria during pregnancy may therefore be viewed
as a primordial preventive strategy against diabetes. Patients with diabetes have
atypical malaria presentations. Glucose-6-phosphate dehydrogenase deficiency,
which is associated with primaquine failure for radical cure is also associated
with dysglycaemia. Type 2 Diabetic mice infected with malaria are more efficient
at infecting mosquitoes. A similar synergy in humans warrants evaluation, which
would then make "diabetic malaria" a public health problem. Metformin has well
known anti-malarial properties. There is significant literature available
highlighting the link between diabetes and malaria, an area warranting active
further research. Metformin as a prophylactic agent for malaria prevention
warrants evaluation.
PMID- 28507381
TI - Sleep hygiene and diabetes: Suggestions for primary care.
AB - Sleep problems are common in chronic disorders like diabetes and are the result
of poor diet and unhealthy lifestyles. Comprehensive management of diabetes
entails lifestyle management and restoration of good habits. Sleep hygiene
maintenance helps persons living with diabetes enjoy a better quality of life by
restoring normal sleep patterns and thereby improving glycaemic control.
PMID- 28507382
TI - Prognostic significance of IDH 1 mutation in patients with glioblastoma
multiforme.
AB - Focus of brain tumour research is shifting towards tumour genesis and genetics,
and possible development of individualized treatment plans. Genetic analysis
shows recurrent mutation in isocitrate dehydrogenase (IDH1) gene in most
Glioblastoma multiforme (GBM) cells. In this review we evaluated the prognostic
significance of IDH 1 mutation on the basis of published evidence. Multiple
retrospective clinical analyses correlate the presence of IDH1 mutation in GBM
with good prognostic outcomes compared to wild-type IDH1. A systematic review
reported similar results. Based on the review of current literature IDH1 mutation
is an independent factor for longer overall survival (OS) and progression free
survival (PFS) in GBM patients when compared to wild-type IDH1. The prognostic
significance opens up new avenues for treatment.
PMID- 28507383
TI - Short-term antibacterial efficacy of a new silver nanoparticle-containing
toothbrush.
PMID- 28507384
TI - Intraosseous access over central venous or peripheral venous line as an initial
means of resuscitation- A possible measure for improving outcomes of cardiac
arrests.
PMID- 28507385
TI - Higher education needs more improvement: The case of Pakistan.
PMID- 28507386
TI - Publish or perish: A sign of caution for authors to avoid predatory journals.
PMID- 28507387
TI - Multidisciplinary approach to the prenatal diagnosis and Post natal management of
a large suprasellar arachnoid cyst: A case report.
AB - Arachnoid cysts are intra-arachnoid sacs filled with cerebrospinal fluid
representing a rare occurence in neonates. We report the case of a suprasellar
arachnoid cyst diagnosed prenatally at 21 weeks gestation on routine obstetric
ultrasound. A cystic lesion was picked up incidentally at routine antenatal scan.
The cyst was noted to be increasing in size over a series of radiological scans.
The cyst was diagnosed as a suprasellar arachnoid cyst compressing the third
ventricle and bilateral lateral ventricles. A left pteryonal craniotomy for
cystocisternostomy of large suprasellar cyst was performed initially. Within a
month the cyst recurred with clinical and radiological evidence. An Endoscopic
Third Ventriculostomy (ETV) with fenestration was performed.The patient was
shifted to the NICU and discharged after 3 days in a stable condition. Patient
was followed after 1 week and reassured and advised for one year follow-up.
PMID- 28507389
TI - Bouncing back across the board: Results of the 2016 CVMA Practice Owners Economic
Survey.
PMID- 28507388
TI - Congenital nuclear cataracts in a Holstein dairy herd.
AB - This report describes congenital nuclear cataracts and posterior lenticonus in a
closed purebred Holstein dairy herd in Canada. Ophthalmic examinations were
completed on 30 male and 249 female cattle aged newborn to 10 years old.
Nutritional, infectious, and toxic etiologies were investigated. Necropsies of 3
affected calves were performed and eyes of 2 additional affected calves were
examined with light microscopy. Bilateral nuclear cataracts were identified in
53/279 (19%) animals. Additional congenital anomalies observed included posterior
lenticonus, iris to lens persistent pupillary membranes (n = 7), and lenticular
colobomata (n = 1). Heifers did not give birth to calves with congenital nuclear
cataracts (0/105), whereas the incidence of affected calves born to multiparous
cows was 31% (53/171). The animals with nuclear cataracts ranged from newborn to
8 years old. The cataracts appeared to be non- or minimally progressive. Light
microscopic examination of 10 affected globes confirmed nuclear cataract with
posterior lenticonus (n = 10). Pedigree analysis was inconclusive. Polymerase
chain reaction and sequence analysis for the NID1 gene deletion were negative.
The etiology of the congenital lenticular anomalies was not determined.
PMID- 28507390
TI - High-quality PVD graphene growth by fullerene decomposition on Cu foils.
AB - We present a new protocol to grow large-area, high-quality single-layer graphene
on Cu foils at relatively low temperatures. We use C60 molecules evaporated in
ultra high vacuum conditions as carbon source. This clean environment results in
a strong reduction of oxygen-containing groups as depicted by X-ray photoelectron
spectroscopy (XPS). Unzipping of C60 is thermally promoted by annealing the
substrate at 800oC during evaporation. The graphene layer extends over areas
larger than the Cu crystallite size, although it is changing its orientation with
respect to the surface in the wrinkles and grain boundaries, producing a
modulated ring in the low energy electron diffraction (LEED) pattern. This
protocol is a self-limiting process leading exclusively to one single graphene
layer. Raman spectroscopy confirms the high quality of the grown graphene. This
layer exhibits an unperturbed Dirac-cone with a clear n-doping of 0.77 eV, which
is caused by the interaction between graphene and substrate. Density functional
theory (DFT) calculations show that this interaction can be induced by a coupling
between graphene and substrate at specific points of the structure leading to a
local sp3 configuration, which also contribute to the D-band in the Raman
spectra.
PMID- 28507391
TI - Electrical Characterization of Glycerin: Water Mixtures: Implications for Use as
a Coupling Medium in Microwave Tomography.
AB - We examine the broadband behavior of complex electrical properties of glycerin
and water mixtures over the frequency range of 0.1 - 25.0 GHz, especially as they
relate to using these liquids as coupling media for microwave tomographic
imaging. Their combination is unique in that they are mutually miscible over the
full range of concentrations which allows them to be tailored to dielectric
property matching for biological tissues. While the resultant mixture properties
are partially driven by differences in the inherent low frequency permittivity of
each constituent, relaxation frequency shifts play a disproportionately larger
role in increasing the permittivity dispersion while also dramatically increasing
the effective conductivity over the frequency range of 1 to 3 GHz. For the full
range of mixture ratios, the relaxation frequency shifts from 17.5 GHz for 0%
glycerin to less than 0.1 GHz for 100% glycerin. Of particular interest is the
fact that the conductivity stays above 1.0 S/m over the 1-3 GHz range for
glycerin mixture ratios (70-90% glycerin) we use for microwave breast tomography.
The high level of attenuation is critical for suppressing unwanted multipath
signals. This paper presents a full characterization of these liquids along with
a discussion of their benefits and limitations in the context of microwave
tomography.
PMID- 28507392
TI - Consumer medicine information.
PMID- 28507393
TI - Treating patients on new anticoagulant drugs.
PMID- 28507394
TI - Treating dental patients on new anticoagulant drugs.
PMID- 28507395
TI - Correcting iron deficiency.
PMID- 28507396
TI - Oral supplements and iron deficiency.
PMID- 28507397
TI - Managing the drug treatment of rheumatoid arthritis.
PMID- 28507398
TI - Managing acute pulmonary oedema.
PMID- 28507399
TI - Managing hepatitis C in general practice.
PMID- 28507401
TI - Economic evaluation of medicines.
PMID- 28507400
TI - Prescribing for people with acute rheumatic fever.
PMID- 28507402
TI - Proton pump inhibitor-associated hypomagnesaemia and hypocalcaemia.
PMID- 28507403
TI - App Review: Drug names.
PMID- 28507404
TI - Ceritinib for non-small cell lung cancer.
PMID- 28507405
TI - Erratum: Long-term prescribing of new oral anticoagulants.
AB - [This corrects the article on p. 200 in vol. 39, PMID: 27990047.].
PMID- 28507406
TI - Evaluation of different agroindustrial waste on the effect of different carcass
characteristics and physiological and biochemical parameters in broilers chicken.
AB - AIM: This study was conducted to evaluate the physiological and biochemical
effect in chickens of the Ross breed of a food enriched with agroindustrial
waste. MATERIALS AND METHODS: The food is one of the main components of the total
cost for the production of chickens. Rations should be formulated to provide the
correct balance of energy, protein, amino acids, minerals, vitamins and essential
fatty acids, to allow optimal growth and performance. This study was intended to
evaluate a natural feed for chicken, made from corn, yucca meal, eggshells,
orange peel, soybean meal, salt and garlic, enriched with agroindustrial waste
(molasses, milk whey and ferment of coffee). The weight gain was evaluated in
broilers using a diet enriched with different agroindustrial wastes, with respect
to a control food of the same composition but not containing residue. To develop
the experiment 120 male Ross 308 chicks were used, these were evaluated for 6
weeks. Physicochemical test for the food and the agroindustrial waste were
performed; moisture was determined; organic carbon, organic material and the ash,
to characterize the agroindustrial wastes, the reducing sugars content using a
spectrophotometer at 540 nm and proteins through the Kjeldahl method was
evaluated. During the experiment, the weight gain of chickens and feed conversion
was evaluated; the end of the experiment the weight of eviscerated channel
relative weight breast, thighs, pancreas, and abdominal fat was determined,
besides including blood chemistries as determination of cholesterol,
triglycerides, and glucose. Finally, the microbiological analyzes to detect the
presence of Escherichia coli in the cecum was determinate. Data were analyzed by
InfoStat statistical program using the generalized linear model procedure. The
statistical comparison was made by Tukey test at the 95% probability level.
RESULTS: After the evaluation, fed chickens with the treatments food + milk whey
(FMW) and food + ferment of coffee (FFC) demonstrated increased from 1949 to 1892
g, respectively, to the 42 days of evaluation, showing the best treatment for
weight gain. However, the FFC treatment showed the best feed conversion reaching
values of 1.79 related to levels of blood glucose (249 mg/dl). Even so the
eviscerated channel yields were higher for the treatment FFC reaching 1810.1 g
unlike the treatment FMW which it reached a weight of 1718.2 g with increased
formation of abdominal fat (7.4 g) unlike other treatments. From the results, it
is concluded that food enriched with coffee ferment allows an increase in weight,
better feed conversion in addition to high production of lean meat. CONCLUSION:
It was shown that the best treatment was the food enriched with the ferment of
coffee, due to increased intake and weight gain at the end of 42 days of the
experiment.
PMID- 28507407
TI - Study on postpartum estrus of guinea pigs (Cavia cobaya) using Anredera
cordifolia leaf extract.
AB - AIM: The purpose of this study was to determine the postpartum estrus cycle of
guinea pigs (Cavia cobaya) using Anredera cordifolia leaf extract. MATERIALS AND
METHODS: Materials used were 8 males and 8 females of C. cobaya with body weight
ranged 400-450 g. Mating ratio applied was 1:1. Treatments given were 0, 10, 50
and 90 mg of A. cordifolia leaf extract/head, designated as T0, T1, T2 and T3,
respectively. Two females were subjected for each treatment. A. cordifolia leaf
extract was administered orally from 10 days prepartum to 10 days postpartum.
Observation of mating behavior, vulva morphology, and vaginal smear preparation
was done in the afternoon for 10 days subsequence postpartum. Data were analyzed
by univariate method and descriptively. RESULTS: The results showed that the
addition of A. cordifolia leaf extract 50 mg orally could accelerate the time of
postpartum estrus based on the average frequency of mating behavior consisting of
behavioral approach, allow the buck to sniffing her, mating positions, standing
heat, lordosis position, and copulation. During estrus, vulva morphology was red
color, had much mucus and no thin membrane covering vagina. There were a lot of
superficial cells on vagina. CONCLUSION: The best treatment to accelerate
occurring postpartum estrus was the addition of A. cordifolia leaf extract as
many as 50 mg/head weight (T2) orally.
PMID- 28507408
TI - Effect of dietary supplementation of fermented fish silage on serum biochemical
parameters of broiler Japanese quails (Coturnix coturnix japonica).
AB - AIM: The objective of this study was to evaluate the effect of feeding fermented
fish silage (FFS) on serum biochemical parameters of Japanese quails (Coturnix
coturnix japonica). MATERIALS AND METHODS: A total of 192, 7-day-old broiler
Japanese quail chicks of either sex, were randomly distributed into four dietary
treatments with four replicates in each group having 12 chicks in each replicate
pen. The dietary treatments were T1 - Control diet, T2 - Diet containing 5% FFS,
T3 - Diet containing 10% FFS, and T4 - Diet containing 15% FFS. Group body weight
and feed consumption were recorded at weekly intervals. Feed conversion ratio
(FCR) was derived by dividing the feed consumed with the weekly body weight gain.
At the end of the experiment, 8 birds from each treatment were selected randomly
and sacrificed by cervical dislocation to study the carcass traits expressed as %
pre-slaughter live weight. At 5 weeks of age, about 2 ml of blood was taken from
the jugular vein of each selected bird, and serum samples were separated after
centrifugation. Total protein, albumin/globulin (A/G) ratio, calcium, phosphorus,
triglyceride, total cholesterol, high density lipoprotein-cholesterol (HDL-C),
very low density lipoprotein-cholesterol (VLDL-C), low density lipoprotein
cholesterol (LDL-C), alanine aminotransferase (ALT), and aspartate
aminotransferase (AST) were estimated in the serum. RESULT: The cumulative body
weight gains from 1 to 5 weeks of age did not vary significantly between control
and 5% FFS group. However, a linear decrease in body weight gain was observed by
increasing the levels of FFS beyond 5% in the diet. The cumulative feed
consumption was significantly higher in case of birds under control group during
1-5 weeks of age as compared to birds fed FFS based diet (5%, 10%, and 15%). No
statistical difference in cumulative feed conversion ratio could be noticed
during 1-5 weeks of age. The eviscerated yield decreased and giblet weight
increased due to the dietary supplementation of FFS at 15% level. The breast meat
yield decreased due to dietary supplementation of FFS at 10% and 15% level in the
diet of broiler Japanese quails. The effect of FFS was found to be nonsignificant
(p>0.05) with respect to serum total protein, globulin and A/G ratio under
different treatments whereas significant difference observed in serum albumin
concentration. Dietary supplementation of FFS at 10% and 15% level significantly
increased the AST concentration in serum. There was no significant difference
among the treatments regarding the parameters such as ALT, calcium, phosphorous,
triglyceride, total cholesterol, HDL-C, VLDL-C, and LDL-C. CONCLUSION: The serum
biochemical parameters are influenced by the dietary supplementation of FFS in
broiler Japanese quails.
PMID- 28507409
TI - Toxoplasma gondii Type I, predominant genotype isolated from sheep in South of
Iran.
AB - AIM: This study was performed to determine the genetic diversity of Toxoplasma
gondii in sheep using nested-polymerase chain reaction-restriction fragment
length polymorphism (PCR-RFLP) in Southern Iran. MATERIALS AND METHODS: The
tissue samples of diaphragm and heart from 125 sheep were collected from the main
slaughterhouses of Jahrom district in South of Fars province, Iran, between
Aprils and June 2013. The DNA were extracted and analyzed by nested-PCR using
specific primers for SAG2 and GRA6 loci. RFLP was used to classify strains into
one of the three major lineages of T. gondii. RESULTS: T. gondii Type I was
predominant in this area. The data obtained from both loci demonstrated that the
frequency of each genotype was 72% Type I, 2.4% Type III, 7.2% mixed Type I and
II, 16.8% mixed Type I and III, 0.8% mixed Type II and III, and 0.8% mixed Type
I, II and III. CONCLUSIONS: Although the previously published data indicated that
Type II is the predominant T. gondii genotype in sheep in the other parts of the
world, this study showed that genotype I is the dominant genotype of T. gondii in
the southern Iran; however, other genotypes were detected. High diversity of T.
gondii genotypes including mix genotypes in lambs is of importance for the public
health. These studies depict a new mapping of T. gondii genotypes pattern which
could be very helpful in toxoplasmosis control and prevention.
PMID- 28507410
TI - Isolation and identification of fungi associated with spoilt fruits vended in
Gwagwalada market, Abuja, Nigeria.
AB - AIM: Annual reports have shown that 20% of fruits and vegetables produced are
lost to spoilage. This study was undertaken to isolate and identify fungi that
are associated with spoilt fruits commonly sold in Gwagwalada market, Abuja, and
recommend appropriate control measure. MATERIALS AND METHODS: The study was
conducted in Gwagwalada metropolis, Gwagwalada Area Council of the Federal
Capital Territory, Abuja, Nigeria. A total of 100 spoilt fruits which include
pawpaw (Carica papaya), orange (Citrus sinensis), tomato (Lycopersicon
esculentum), pineapple (Ananas comosus), and watermelon (Citrullus vulgaris) were
purchased and examined for the presence of fungal organisms using standard
methods. The data collected were analyzed using simple descriptive statistics
(frequency and mean) and analysis of variance (p<0.05). RESULTS: Aspergillus
niger had the highest occurrence in pineapple, watermelon, oranges, pawpaw, and
tomatoes with a frequency of 38%. Fusarium avenaceum followed with the frequency
of occurrence of 31% in fruits such as pineapple, watermelon, oranges, pawpaw,
and tomatoes while Penicillium digitatum and Rhizopus stolonifer had the least
frequency of 4% each in tomato; and orange and tomato, respectively. Other fungal
species were identified as yeast (Saccharomyces species) (10%), Fusarium solani
(8%), and Aspergillus flavus (5%). The highest prevalence rate was 70% of A.
niger from orange followed by F. avenaceum of which 65% isolates were recovered
from pawpaw. Other fungal organisms such as yeast (Saccharomyces species), P.
digitatum and R. stolonifer were isolated with varying prevalence (40%, 20%, and
5%) from watermelon, tomato, and orange, respectively. However, there was no
significant difference in the fungal load of the various fruits studied (analysis
of variance=478.2857, p<0.05, F=4.680067 and df=34). CONCLUSION: The pathogenic
fungi species associated with fruits spoilage in this study are of economical and
public health significance. A. niger causes black mold in certain fruits and
vegetables. Some strains of A. niger have been reported to produce potent
mycotoxins called ochratoxins that can be harmful to human beings and animals.
Care should be taken during handling of these fruits and improved technology
based preservation methods are suggested to enhance the keeping quality of
fruits.
PMID- 28507411
TI - Cross-sectional study on bovine mastitis and its associated risk factors in Ambo
district of West Shewa zone, Oromia, Ethiopia.
AB - AIM: A cross-sectional study was conducted to estimate the prevalence and
associated risk factors of mastitis in dairy cows. MATERIALS AND METHODS: A total
of 302 dairy cows were selected from all volunteer dairy farms in Ambo district
of West Shewa Zone, Oromia region. Thorough clinical examination was made on all
lactating cows for evidence of signs of clinical mastitis followed by collection
of milk sample for examination of gross changes of milk secretion and California
mastitis test. RESULT: About 126 (41.7%) cows had mastitis, of which 9.9%
(30/302) were clinical and 32.8% (96/302) were subclinical mastitis cases. The
quarter level prevalence was 44.4% (536/1208), comprising 9.3% (112/1208),
clinical and 32.8% (396/1208) subclinical forms of mastitis. In addition, 5.5%
(66/1208) of teats were found to be blind on the clinical examination of udder
and teat. The Chi-square analysis of intrinsic risk factors revealed
significantly (p<0.05) higher prevalence of mastitis in crossbred cattle (47.2%)
than indigenous (15.4%), in cattle above 7 years (75%) than less than 2-6 years
of age (28%) and cows given more than 4 calves (81.3%) than those with less than
4 calves (31.1%) irrespective to their lactation stage. There was also
significantly (p<0.05) higher mastitis prevalence in larger (46.6%) than smaller
herds (24.2%) and among the farming systems in semi-intensive (47.1%) and
intensive (42.3%) than extensive (8.1%) management system. CONCLUSION: This study
indicated a higher prevalence of mastitis linked with several risk factors. Thus,
early diagnosis and regular screening of cows for subclinical mastitis together
with proper therapeutic management of clinical cases are of paramount importance.
Moreover, control and prevention strategies should be designed and implemented
with great emphasis given to risk factors to reduce bovine mastitis and its
impact on milk production and food security.
PMID- 28507412
TI - The effects of quercetin on microRNA and inflammatory gene expression in
lipopolysaccharide-stimulated bovine neutrophils.
AB - AIM: To investigate gene expression of microRNA (miRNA) milieus (MIRLET7E, MIR17,
MIR24-2, MIR146A, and MIR181C), inflammatory cytokine genes (interleukin 1beta
[IL1B], IL6, CXCL8, and tumor necrosis factor [TNF]), and the pathogen receptor
toll-like receptor (TLR4) in bovine neutrophils under quercetin supplementation.
MATERIALS AND METHODS: Isolated bovine neutrophils were incubated with bacterial
lipopolysaccharide under quercetin treatment or left untreated. Real-time
polymerase chain reaction was performed to determine the expression of the miRNAs
and messenger RNA (mRNA) transcripts in neutrophils. RESULTS: Quercetin-treated
neutrophils exhibited a remarkable suppression in MIR24-2, MIR146A, and MIR181C
expression. Similarly, mRNA expression of IL1B, IL6, CXCL8, TLR4, and TNF genes
noticeably declined in the quercetin group. Many proinflammatory genes (IL1B,
IL6, and CXCL8) and the pathogen receptor TLR4 had a negative correlation with
MIR146A and MIR181C as revealed by Pearson correlation. CONCLUSIONS: Interaction
between cognate mRNAs and miRNAs under quercetin supplementation can be
summarized as a positive or negative correlation. This finding may help
understand the effects of quercetin either on miRNA or gene expression during
inflammation, especially as a potentially applicable indicator in bovine
mastitis.
PMID- 28507413
TI - Prevalence of echinococcosis and Taenia hydatigena cysticercosis in slaughtered
small ruminants at the livestock-wildlife interface areas of Ngorongoro,
Tanzania.
AB - AIM: Echinococcosis or hydatidosis (due to the larval stage of Echinococcus spp.)
and cysticercosis (due to the larval stage of Taenia hydatigena) pose a
significant economic losses due to slaughter condemnation and risk to public
health in developing countries such as Tanzania where sanitation is poor and
people live in close proximity with each other and with animals. This study was
conducted to determine the prevalence of and to identify the predisposing factors
for echinococcosis and cysticercosis in sheep and goats at three slaughter slabs
located in the livestock-wildlife interface areas of Ngorongoro, Tanzania.
MATERIALS AND METHODS: A cross-sectional based survey was conducted, from January
2013 to April 2013, whereby a total of 180 animals comprising 90 goats and 90
sheep of both sexes were examined at postmortem for the evidence of larval stages
of Echinococcus spp. (hydatid cyst) and T. hydatigena (Cysticercus tenuicollis)
through visual inspection, incision and palpation of organs and viscera. RESULTS:
The prevalence of echinococcosis was 22.2% and 16.6%, in goats and sheep,
respectively, while the overall infection rates for cysticercosis were 61.1% in
goats and 42.2% in sheep. The result of this study revealed that goats and sheep
in Malambo slaughter slab had significantly higher prevalence of T. hydatigena
(C. tenuicollis) and hydatid cysts (p<0.05) compared to other slab points. T.
hydatigena (C. tenuicollis) cysts were more frequently detected in the omentum
than other visceral organs among the animals examined. CONCLUSION: In conclusion,
the observed high prevalence of the two metacestodes larval stages leads to high
condemnation rates of edible offals and raises significant public health
concerns. This underscores for the need to undertake more extensive
epidemiological investigations to better determine the causal factors, economic
impact, and public health importance of the disease in this livestock-wildlife
interface setting.
PMID- 28507414
TI - A reducing trend of fasciolosis in slaughtered animals based on abattoir data in
South of Iran.
AB - AIM: Fascioliasis is a zoonosis infection caused by the liver trematodes
(Fasciola spp.) which have been considered to be an important disease in
livestock. After several large outbreaks, fascioliasis remains one of the serious
health concerns of Iran. This study was conducted to evaluate the prevalence and
possible trends of fascioliasis in slaughtered animals in South of Iran based on
abattoir data during a period of 5 years. MATERIALS AND METHODS: The daily
records for cattle, sheep, and goats slaughtered in the abattoir were extracted
from the archived documents of the recent 5 years (2011-2015) and used as the
source of data. The collected data were statistically analyzed for finding any
probable correlation between the various factors associated with fasciolosis.
RESULTS: Our results showed that 3.44% of all slaughtered animals during 2011
2015 were infected with Fasciola spp. The mean prevalence of fasciolosis for
cattle, sheep, and goat was 11.15%, 5.22%, and 2.15%, respectively. In addition,
the highest infection rate was in winter (4.02%), and the lowest were entered in
summer (2.86%). CONCLUSION: Our findings showed a reducing trend during the 5
years. Improving the animal husbandry and increasing the awareness through
fasciolosis may be a logical explanation for this trend. Since there have been
suggested numerous factors associated with the epidemiology of fasciolosis,
further studies seem essential for better clarifying the various aspects of
fasciolosis in areas.
PMID- 28507415
TI - Prospects of complete feed system in ruminant feeding: A review.
AB - Effective utilization of available feed resources is the key for economical
livestock rearing. Complete feed system is one of the latest developments to
exploit the potential of animal feed resources in the best possible way. The
complete feed is a quantitative mixture of all dietary ingredients, blended
thoroughly to prevent separation and selection, fed as a sole source of nutrients
except water and is formulated in a desired proportion to meet the specific
nutrient requirements. The concentrate and roughage levels may vary according to
the nutrient requirement of ruminants for different production purposes. The
complete feed with the use of fibrous crop residue is a noble way to increase the
voluntary feed intake and thus animal's production performance. In this system of
feeding, the ruminant animals have continuous free choice availability of uniform
feed mixture, resulting in more uniform load on the rumen and less fluctuation in
release of ammonia which supports more efficient utilization of ruminal non
protein nitrogen. Feeding complete diet stabilizes ruminal fermentation, thereby
improves nutrient utilization. This feeding system allows expanded use of agro
industrial by-products, crop residues and nonconventional feeds in ruminant
ration for maximizing production and minimizing feeding cost, thus being
increasingly appreciated. However, to extend the concept extensively to the field
and make this technology successful and viable for farmers, more efforts are
needed to be taken.
PMID- 28507416
TI - Pathotypic characterization of Newcastle disease virus isolated from vaccinated
chicken in West Java, Indonesia.
AB - AIM: This research was conducted to differentiate and characterize eight
Newcastle disease virus (NDV) isolates collected from vaccinated chicken at
commercial flocks in West Java, Indonesia, in 2011, 2014 and 2015 by pathotype
specific primers. MATERIALS AND METHODS: A total of eight NDV isolates collected
from clinical outbreaks among commercial vaccinated flocks in West Java,
Indonesia, in 2011, 2014, and 2015 were used in this study. Reverse transcription
polymerase chain reaction was used to detect and differentiate virulence of NDV
strains, using three sets of primers targeting their M and F gene. First primers
were universal primers to detect NDV targeting matrix (M) gene. Other two sets of
primers were specific for the fusion (F) gene cleavage site sequence of virulent
and avirulent NDV strains. RESULTS: Our results showed that three isolates belong
to NDV virulent strains, and other five isolates belong to NDV avirulent strains.
The nucleotide sequence of the F protein cleavage site showed 112K/R-R-Q/R-K-R/G
F117 on NDV virulent strains and 112G-K/R-Q-G-R-L117 on NDV avirulent strain.
CONCLUSION: Result from the current study suggested that NDV virulent strain were
circulating among vaccinated chickens in West Java, Indonesia; this might possess
a risk of causing ND outbreaks and causing economic losses within the poultry
industry.
PMID- 28507417
TI - Molecular detection of Taenia spp. in dogs' feces in Zanjan Province, Northwest
of Iran.
AB - AIM: Echinococcus and Taenia spp. are important but neglected zoonotic helminths
of dogs. Dogs as the most relevant definitive hosts harbor several species of
Taenia and Echinococcus simultaneously in their gastrointestinal lumen which are
morphologically indistinguishable. In this study, we used a multiplex polymerase
chain reaction (PCR) method to identify Taeniid infections which seem to be
highly distributed in the study region. MATERIALS AND METHODS: A total of 450 dog
fecal samples were collected from eight different areas of Zanjan province,
northwest of Iran, and examined using a flotation method followed by multiplex
PCR for detection and identification of parasites' eggs. RESULTS:
Gastrointestinal parasites were found in 86 out of 450 fecal samples (19.1%) by
microscopic examination. Taeniid eggs were observed in 5.6% of samples,
containing 0.45%, 3.8%, and 1.3% Echinococcus granulosus, Taenia spp., and mix
infection of both E. granulosus and Taenia spp., respectively. Echinococcus
multilocularis was absent in the samples. CONCLUSION: A relatively low rate of E.
granulosus (1.8%) was observed in this study. However, risks of this parasite
should not be overlooked, and control programs need to be extended for this
species and other Taeniid spp. In particular, dogs are recommended to be dewormed
more frequently.
PMID- 28507418
TI - Spatial pattern of foot-and-mouth disease virus serotypes in North Central
Nigeria.
AB - AIM: This study aimed to determine the foot-and-mouth disease virus (FMDV)
serotypes circulating, the prevalence of FMDV serotypes, and the spatial
distribution of FMDV among sedentary and pastoral cattle herds in the North
Central Nigeria. MATERIALS AND METHODS: A cross-sectional study was undertaken,
during which a total of 155 sera that tested positive for foot-and-mouth disease
(FMD) 3ABC non-structural protein antibodies were selected and screened for FMD
structural protein serotypes, A, O, SAT 1, and SAT 2 using a solid-phase
competitive enzyme-linked immunosorbent assay (ELISA). Epithelial tissue
specimens were collected during outbreak investigations which were tested for FMD
using an antigen capture ELISA for serotype A, O, SAT 1, and SAT 2. RESULTS: An
overall serotype-specific prevalence of 79.35 (95% confidence interval [CI]: 72.4
85.18) was recorded for serotype O, 65.2% (95% CI: 57.41-72.3) for serotype A,
52.9% (95% CI: 45.03-60.67) for SAT 2, and 33.55% (95% CI: 26.45-41.26) for SAT
1. Evidence of exposure to multiple FMDV serotypes showed that 12.26% of the sera
samples had antibodies against four serotypes circulating, 30.97% had antibodies
against three serotypes circulating, 22.58% had antibodies against two serotypes,
and 17% showed exposure to only one serotype. Clinical specimens (epithelial
tissue) collected during outbreak investigations showed that serotype O has the
highest proportion of 50% with serotype A - 25%; SAT 2 - 20.8%; and SAT 1 - 4.1%.
CONCLUSION: The study detected diffuse and co-circulation of serotypes A, O, SAT
1, and SAT 2 within the study area, and hence the need for the appropriately
matched multivalent vaccine is strongly advocated for FMD control in Nigeria.
PMID- 28507420
TI - Some hematological and biochemical parameters of different goat breeds in
Sultanate of Oman "A preliminary study".
AB - AIM: In Sultanate of Oman, goats are considered as one of the most important
livestock in which there are many breeds of goat such as Batinah, Jabali,
Dhofari, Jabal Al-Akhdar, Sahrawi, and Sahrawi Musandam. Little hematological and
biochemical information is known on Omani goat breeds; therefore, the main
purpose of this study was to determine reference baseline data regarding
hematological and biochemical values of different Omani goat breeds. MATERIALS
AND METHODS: A total of 30 healthy animals of different Omani goat breeds
(Jabali, Jabal Al-Akhdar, Sahrawi, and Sahrawi Musandam) were selected randomly
from different areas in Sultanate of Oman. The blood samples were collected from
the jugular vein into two tubes for blood hematology and biochemical analysis.
Statistical analysis was applied by using GraphPad Prism 7 software to calculate
the minimum and maximum values to determine the range, mean, standard deviation
of the mean and the p value. RESULTS: No statistically significant variation in
most hematological and biochemical parameters was found among the Omani goat
breeds. The results of blood hematology revealed that the mean white blood cells
(14.6+/-3.32 *103/uL), and the percentage of neutrophils in Omani goats (60.87+/
8.46%) were higher than that in most goat breeds. Higher values of red blood
cells (12.8+/-1.28 *106/uL), hemoglobin (10.4+/-1.92 g/dl), hematocrit (38.29+/
4.06%), and lower values of mean corpuscular HGB concentration (27.05+/-3.5 g/dl)
were observed in Omani goat breeds comparing to that in the other goat breeds.
Lower values of total bilirubin (0.22+/-0.03 mg/dl), blood urea nitrogen (14.62+/
2.66 mg/dl), and cholesterol (48.58+/-19.05 mg/dl) were found in Omani goat
breeds when compared to that of the other goat breeds. CONCLUSION: The obtained
results are considered as the first values to be published for the different
Omani goat breeds. This study is considered as preliminary study which can be
used as a reference for further studies to determine reference values for the
studied breeds to aid the veterinarians in the interpretation of the laboratory
data and for the selection of the appropriate treatment.
PMID- 28507419
TI - Exploring the potential hazard of Mycobacterium avium subspecies paratuberculosis
as a cause for Crohn's disease.
AB - BACKGROUND: Mycobacterium avium subspecies paratuberculosis (MAP) is the
causative agent of Johne's disease (JD), or paratuberculosis in ruminants has
been suspected to be implicated in the pathogenesis of Crohn's disease (CD) in
humans with chronic inflammatory intestinal changes. As the hypothesis is now
fast being recognized that MAP could possibly be the etiological agent of CD
which is found to be excreted in milk of dairy animals subclinically or
terminally ill with JD. AIM: The present study was aimed to detect MAP in milk by
polymerase chain reaction (PCR) targeting IS900 and to describe the excretion
pattern of MAP in milk from asymptomatic lactating cows and does with relevance
to the public health significance. MATERIALS AND METHODS: A total of 77 milk
samples were collected randomly from lactating animals which include cows (45)
and does (32). All the 77 milk samples were processed to identify the presence of
MAP by employing the direct IS900 PCR as per the standard protocol. RESULTS: Out
of 77 milk samples from asymptomatic lactating animals, 12 (15.58%) were showed
positivity for IS900 PCR in which 5 (11.11%) were from lactating cows and 7
(21.87%) were from lactating does. CONCLUSION: In our study, 15.58% of milk
samples showed IS900 positivity which indicates the presence of subclinical MAP
infection in lactating animals. Hence, there is a possibility for excretion of
MAP through milk which can be a potential threat for CD in humans by raw milk
consumption. Therefore, the prevention of MAP in the food chain need to be
assured by sourcing raw products from animal herds free of MAP infection.
PMID- 28507421
TI - Orthopaedic tumors: What problems are we solving, and are universities and major
medical centers doing enough?
AB - Little has been published about the complexity of orthopaedic tumors compared to
others tumors. The current study in the literature treated this problem in terms
of classification, surgical intervention and impact on the patient. In this
article, factors risks of tumors will be we identified. A strategy based on three
dimensional simulations will be explained in order to improve the clinical
trials.
PMID- 28507422
TI - Understanding the Spectrum of SLC2A1-Associated Disorders.
AB - Investigators from the Danish Epilepsy Center the frequency of SLC2A1 mutations
in a cohort of patients with different types of epilepsies.
PMID- 28507423
TI - Lacosamide in Pediatric Status Epilepticus.
AB - Investigators from Baylor College of Medicine studied the efficacy of lacosamide
in pediatric status epilepticus (SE).
PMID- 28507424
TI - Migraine, Celiac Disease and Intestinal Microbiota.
AB - Investigators from four European tertiary care hospitals (in Paris, France;
Milan, Udine and Perugia, Italy) performed a case-control study of children and
adolescents aged 6 to 17 years diagnosed with primary headaches in the emergency
department by a pediatric neurologist using the validated ICHD-3 criteria.
PMID- 28507425
TI - A Multigroup, Longitudinal Study of Truant Youths, Marijuana Use, Depression, and
STD-Associated Sexual Risk Behavior.
AB - Truant youth are likely to engage in a number of problem behaviors, including
sexual risky behaviors. Previous research involving non-truant youth has found
sexual risk behaviors to be related to marijuana use and depression, with
differential effects for male and female youth. Using data collected in a NIDA
funded, prospective intervention project, results are reported of a male-female,
multi-group, longitudinal analysis of the relationships among truant youth
baseline sexual risk behavior, marijuana use, and depression, and their sexual
risk behavior over four follow-up time points. Results indicated support for the
longitudinal model, with female truants having higher depression scores, and
showing stronger relationships between baseline depression and future engagement
in sexual risk behavior, than male truants. Findings suggest that incorporating
strategies to reduce depression and marijuana use may decrease youth sexual risk
behavior.
PMID- 28507427
TI - The Sensimed Triggerfish contact lens sensor: efficacy, safety, and patient
perspectives.
AB - Intraocular pressure, a major modifiable risk factor for glaucoma, has been shown
to fluctuate throughout the day in patients with glaucoma. The detection and
measurement of this fluctuation may help guide the clinical management of
glaucomatous individuals. The Sensimed Triggerfish contact lens sensor (CLS),
which has recently gained approval for marketing in the USA, is designed to
detect intraocular pressure-related changes in an eye over a 24-hour period. This
review will provide an overview of the Triggerfish CLS, as well as summarize
current clinical data pertaining to the device. Overall, the current evidence
suggests that the Triggerfish CLS is safe and well tolerated, and provides
reproducible results. One challenge of using the Triggerfish CLS is that it may
only provide data on relative changes in intraocular pressure rather than
absolute intraocular pressure. In addition, its validity at estimating
intraocular pressure compared to other methods is still controversial. Despite
these limitations, recent studies suggest a myriad of potential indications for
the Triggerfish CLS, including predicting glaucomatous progression and predicting
efficacy of glaucoma treatment. With further research, the Triggerfish CLS may
become a useful tool for eye care practitioners.
PMID- 28507426
TI - Performance of High School Students in a Laparoscopic Training Program.
AB - BACKGROUND AND OBJECTIVES: We hypothesized that high school students can be
subjected to the same laparoscopic surgical training curriculum used by surgeons
and successfully complete it. The goal of this study was to evaluate the
appropriateness of early training in minimally invasive surgical techniques.
METHODS: Thirteen high school students, ages 15-18, participated in the validated
Top Gun Surgeon Laparoscopic Skills and Suturing program. The students performed
3 preparatory drills 10 times each. The students' scores were then compared to a
database of 393 surgeons. Performance graphs were prepared to allow comparison of
skills acquisition between the 2 training groups. RESULTS: All 13 students
successfully completed the tasks. The Students' performance (expressed as
time/percentile range/average percentile) for each task were as follows: rope
pass 101.8 seconds/3.8-47.1/11.8; bean drop 149.5 seconds/18.7-96.0/59.4;
triangle transfer 303.2 seconds/1.3-16.0/5.8. The students started each drill
with slower times, but their average improvement (decreased time to complete
tasks) was more rapid than that of the surgeons between the first and second
trials for each drill (-83 seconds vs -25 seconds, -120 seconds vs -53 seconds,
100 seconds vs -60 seconds). Average student times compared to average surgeon
times during the last trials measured were not significantly different in the
triangle transfer and rope pass drills (P = .40 and .18, respectively). Students'
times were significantly faster than surgeons' in the last measured trial of the
bean drop (P = .039). CONCLUSIONS: Despite the small sample size, this
investigation suggests that high school students can successfully complete skill
building programs in minimally invasive surgery. Further study is needed to
evaluate the appropriateness of starting surgical training of future residents at
an earlier stage of their careers.
PMID- 28507429
TI - Factors associated with the attitudes of oncology nurses toward hospice care in
China.
AB - OBJECTIVE: To examine factors that are associated with the apprehension levels of
oncology nurses toward hospice care. Factors examined in this study included
demographics, nursing experience, education levels, title and post, personal
experiences, and attitudes toward end-of-life care. METHODS: Questionnaires were
provided to nurses (n=201) from three first-tier hospitals in China. A
quantitative scale, Professional End-of-life Care Attitude Scale (PEAS), was used
to assess personal and professional apprehension levels toward hospice care. The
PEAS was translated to Chinese with terms adapted to the cultural environment in
China. Statistical analyses were performed to examine the relationships between
the apprehension levels and various factors. RESULTS: The total PEAS scores
exhibited internal consistency and reliability, with a Cronbach alpha=0.897 and
Pearson's r=0.9030. Of the 201 nurses, 184 provided a valid response (91.5%).
Education level was significantly correlated with personal (P<0.01) and
professional apprehension levels (P<0.05). Higher apprehension level was found in
nurses with less education. CONCLUSION: The PEAS quantitative survey is useful
for evaluating apprehension levels of nurses toward hospice care. Nurses with
more education experienced less anxiety when providing care for terminally ill
patients. The findings suggested that education programs on hospice care could be
strengthened to help nurses cope with negative attitudes toward end-of-life care.
PMID- 28507430
TI - Investigating the feasibility of text message reminders to improve adherence to
nebulized medication in children and adolescents with cystic fibrosis.
AB - BACKGROUND: Children with cystic fibrosis (CF) often have suboptimal adherence
rates to nebulized medication. Adherence barriers cited include forgetting to
take the nebulizers, due to busy home and social lives. Text message reminders
have been shown to be effective at improving adherence rates in other chronic
diseases such as asthma and diabetes. OBJECTIVE: The objective of this study was
to assess the feasibility and efficacy of sending text reminders for a prolonged
period of time to children with CF. MATERIALS AND METHODS: Children with CF aged
5-16 years taking at least one medication via a nebulizer with an electronic
adherence monitor were consented for the study. Text message reminders were sent
to participants and/or parents via the hospital's automated text service, up to
twice a day, for 6 months. The adherence rates for the 6-month text period were
compared to the previous 6 months before the study. Rates were calculated for
weekdays, weekends, and school holidays. RESULTS: Seventeen participants were
recruited to the study, with a mean age of 12 years and a mean forced expiratory
volume in 1 second (FEV1) of 81% predicted. Fifteen children completed the 6
month text period, and I-neb data were accurately analyzed for 13 participants.
The mean adherence rate in the 6 months receiving texts was 80%, compared to 81%
in the prior 6 months. Overall adherence rates on weekdays, weekends, and school
holidays were equivalent during the 2 time periods. A subgroup of patients with
moderate baseline adherence showed increased adherence during the text period,
particularly at weekends. CONCLUSION: It is feasible to send text message
reminders to children with CF, and they are amenable to this approach. Although
text reminders do not increase rates in patients with existing optimal adherence,
they may be of value in patients with more moderate baseline rates.
PMID- 28507428
TI - Propranolol therapy for infantile hemangioma: our experience.
AB - OBJECTIVE: Hemangiomas are the most common benign vascular tumors of infancy.
Although most infantile hemangiomas (IHs) have the ability to involute
spontaneously after initial proliferation and resolve without consequence,
intervention is required in a subset of IHs, which develop complications
resulting in ulceration, bleeding, or aesthetic deformity. The primary treatment
for this subset of IHs is pharmacological intervention, and propranolol has
become the new first-line treatment for complicated hemangiomas. Here, we
evaluated the efficacy of propranolol on proliferation IH in a clinical cohort
including 578 patients. METHODS: We retrospectively reviewed a total of 578 IH
patients who were treated with oral propranolol from January 2010 to December
2012. Responses to the propranolol treatment were graded as: excellent, good,
poor, or no response. Based on the response to propranolol treatment (once daily
at a dose of 1.0 mg/kg for patients younger than 2 months; twice daily at daily
total dose of 2 mg/kg for patients older than 2 months), additional
pharmacotherapies or surgery were used for IH patients for satisfactory clinical
outcome. RESULTS: Five hundred and sixty (96.9%) of 578 IH patients in our study
responded to oral propranolol treatment, and the response rate was significantly
different for different ages of patients (P<0.05), with the youngest patients
having the highest response rate. The mean time of treatment was 6 months (range,
3-12 months). For example, response rate to propranolol was 98.1% in patients
younger than 2 months, compared with 93.3% in patients older than 2 months and
younger than 8 months, and 73.7% in patients older than 8 months. One hundred and
thirty one patients who exhibited incompletely involuted hemangiomas were further
treated with timolol maleate (n=89) or pulsed dye laser (n=42). One hundred and
seventeen (89.3%) of 131 patients showed a positive response. There were no
instances of life-threatening complications after propranolol. However, minor
side effects were observed including 10 (1.73%) cases of sleep disturbance, 7
(1.21%) cases of diarrhea, and 5 (0.86%) cases of bronchospasm. CONCLUSION: IH
requires early intervention. During the involution phase, tapering propranolol
dosage can be done to minimize side effects before discontinuing treatment. For
patients exhibiting telangiectasia and chromatosis after propranolol treatment,
administration of a 0.5% solution of timolol maleate or pulse dye laser is an
effective therapeutic approach for complete involution.
PMID- 28507431
TI - Targeted drugs for pulmonary arterial hypertension: a network meta-analysis of 32
randomized clinical trials.
AB - BACKGROUND: Pulmonary arterial hypertension (PAH) is a devastating disease and
ultimately leads to right heart failure and premature death. A total of four
classical targeted drugs, prostanoids, endothelin receptor antagonists (ERAs),
phosphodiesterase 5 inhibitors (PDE-5Is), and soluble guanylate cyclase
stimulator (sGCS), have been proved to improve exercise capacity and hemodynamics
compared to placebo; however, direct head-to-head comparisons of these drugs are
lacking. This network meta-analysis was conducted to comprehensively compare the
efficacy of these targeted drugs for PAH. METHODS: Medline, the Cochrane Library,
and other Internet sources were searched for randomized clinical trials exploring
the efficacy of targeted drugs for patients with PAH. The primary effective end
point of this network meta-analysis was a 6-minute walk distance (6MWD). RESULTS:
Thirty-two eligible trials including 6,758 patients were identified. There was a
statistically significant improvement in 6MWD, mean pulmonary arterial pressure,
pulmonary vascular resistance, and clinical worsening events associated with each
of the four targeted drugs compared with placebo. Combination therapy improved
6MWD by 20.94 m (95% confidence interval [CI]: 6.94, 34.94; P=0.003) vs
prostanoids, and 16.94 m (95% CI: 4.41, 29.47; P=0.008) vs ERAs. PDE-5Is improved
6MWD by 17.28 m (95% CI: 1.91, 32.65; P=0.028) vs prostanoids, with a similar
result with combination therapy. In addition, combination therapy reduced mean
pulmonary artery pressure by 3.97 mmHg (95% CI: -6.06, -1.88; P<0.001) vs
prostanoids, 8.24 mmHg (95% CI: -10.71, -5.76; P<0.001) vs ERAs, 3.38 mmHg (95%
CI: -6.30, -0.47; P=0.023) vs PDE-5Is, and 3.94 mmHg (95% CI: -6.99, -0.88;
P=0.012) vs sGCS. There were no significant differences in all-cause mortality
and severe adverse events between prostanoids, ERAs, PDE-5Is, sGCS, combination
therapy, and placebo. CONCLUSION: All targeted drugs for PAH are associated with
improved clinical outcomes, especially combination therapy. However, all these
drugs seem to show less favorable effects on survival in the short-term follow
up, suggesting further clinical trials are required.
PMID- 28507432
TI - The effects of patient and physician characteristics on early outpatient
satisfaction with substance dependence care: results of the SUBUSQOL study.
AB - BACKGROUND: Although patient perceptions of health care have increasingly been
explored in the literature, little is known about care satisfaction among
individuals with substance dependence. This exploratory study assessed the
relationships between patient and physician characteristics and early outpatient
satisfaction with care for alcohol and opioid dependence. METHODS: Satisfaction
was assessed using a multidimensional, self-administered and validated
questionnaire during the early care process among a prospective outpatient
cohort. In addition to measuring satisfaction and obtaining sociodemographic and
clinical data, this study collected data on the self-reported health status and
physician characteristics at inclusion. Cross-sectional analysis with multiple
linear regression was performed to identify the variables associated with
satisfaction level. RESULTS: A total of 249 outpatients were included, and 63.8%
completed the satisfaction questionnaire. Patients without a history of previous
care for substance dependence were more satisfied with the appointment-making
process (beta=7.2; P=0.029) and with the doctor consultation (beta=10.3; P=0.003)
than those who had received care previously. Neither sociodemographic
characteristics nor self-reported health status was associated with outpatient
satisfaction. CONCLUSION: The factors that affect patients' ratings of early
satisfaction with the care that they receive should be studied further because
increased understanding of the factors that negatively affect these ratings might
enable caregivers and outpatient management facilities to improve the patient
experience during the early stages of care, which might in turn improve treatment
adherence, continuity of care, and other health-related outcomes.
PMID- 28507433
TI - Effect of pharmaceutical care on clinical outcomes of outpatients with type 2
diabetes mellitus.
AB - BACKGROUND: In the People's Republic of China, outpatients have limited time with
their physicians. Thus, compared to inpatients, outpatients have lower medication
adherence and are less knowledgeable about their disease. OBJECTIVE: The
objective of this study was to evaluate the effect of pharmaceutical care on
clinical outcomes of outpatients with type 2 diabetes mellitus (T2DM). PATIENTS
AND METHODS: A randomized, controlled, prospective clinical trial was conducted
recruiting a total of 240 T2DM outpatients from Zhongda Hospital, Southeast
University. The control group (CG) received only common care from medical staff,
whereas the inter vention group (IG) received extra pharmaceutical care from
clinical pharmacists. Biochemical data such as blood pressure (BP), fasting blood
glucose (FBG), glycosylated hemoglobin A1 (HbA1c), and blood lipid were collected
before and after 6-month intervention. The primary end points in this study were
FBG and HbA1c. RESULTS: After the intervention, most of the baseline clinical
outcomes of the patients in IG significantly improved, while only body mass
index, diastolic BP, low-density lipoprotein cholesterol, and total cholesterol
(TC) improved significantly in patients in the CG. Compared to CG, in IG, there
were significant improvements in FBG, HbA1c, TC, the target attainment rates of
HbA1c, and BP. CONCLUSION: Pharmaceutical care provided by clinical pharmacists
could improve the control of diabetes of outpatients, and clinical pharmacists
could play an important role in diabetes management.
PMID- 28507434
TI - Enhanced oral bioavailability of valsartan using a polymer-based supersaturable
self-microemulsifying drug delivery system.
AB - A novel, supersaturable self-microemulsifying drug delivery system (S-SMEDDS) was
successfully formulated to enhance the dissolution and oral absorption of
valsartan (VST), a poorly water-soluble drug, while reducing the total quantity
for administration. Poloxamer 407 is a selectable, supersaturating agent for VST
containing SMEDDS composed of 10% Capmul(r) MCM, 45% Tween(r) 20, and 45%
Transcutol(r) P. The amounts of SMEDDS and Poloxamer 407 were chosen as
formulation variables for a 3-level factorial design. Further optimization was
established by weighting different levels of importance on response variables for
dissolution and total quantity, resulting in an optimal S-SMEDDS in large
quantity (S-SMEDDS_LQ; 352 mg in total) and S-SMEDDS in reduced quantity (S
SMEDDS_RQ; 144.6 mg in total). Good agreement was observed between predicted and
experimental values for response variables. Consequently, compared with VST
powder or suspension and SMEDDS, both S-SMEDDS_LQ and S-SMEDDS_RQ showed
excellent in vitro dissolution and in vivo oral bioavailability in rats. The
magnitude of dissolution and absorption-enhancing capacities using quantity-based
comparisons was in the order S-SMEDDS_RQ > S-SMEDDS_LQ > SMEDDS > VST powder or
suspension. Thus, we concluded that, in terms of developing an effective SMEDDS
preparation with minimal total quantity, S-SMEDDS_RQ is a promising candidate.
PMID- 28507437
TI - Changing health care culture: a prerequisite to improving patient safety.
PMID- 28507436
TI - Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (epsilon
caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer
metastasized to bone.
AB - Treatment of cancer metastasized to bone is still a challenge due to
hydrophobicity, instability, and lack of target specificity of anticancer drugs.
Poly (ethylene glycol)-poly (epsilon-caprolactone) polymer (PEG-PCL) is an
effective, biodegradable, and biocompatible hydrophobic drug carrier, but lacks
bone specificity. Polyaspartic acid with eight peptide sequences, that is,
(Asp)8, has a strong affinity to bone surface. The aim of this study was to
synthesize (Asp)8-PEG-PCL nanoparticles as a bone-specific carrier of hydrophobic
drugs to treat cancer metastasized to bone. 1H nuclear magnetic resonance,
Fourier transform infrared spectroscopy, and transmission electron microscopy
data showed that (Asp)8-PEG-PCL nanoparticles (size 100 nm) were synthesized
successfully. (Asp)8-PEG-PCL nanoparticles did not promote erythrocyte
aggregation. Fluorescence microscopy showed clear uptake of Nile red-loaded
(Asp)8-PEG-PCL nanoparticles by cancer cells. (Asp)8-PEG-PCL nanoparticles did
not show cytotoxic effect on MG63 and human umbilical vein endothelial cells at
the concentration of 10-800 MUg/mL. (Asp)8-PEG-PCL nanoparticles bound with
hydroxyapatite 2-fold more than PEG-PCL. Intravenously injected (Asp)8-PEG-PCL
nanoparticles accumulated 2.7-fold more on mice tibial bone, in comparison to PEG
PCL. Curcumin is a hydrophobic anticancer drug with bone anabolic properties.
Curcumin was loaded in the (Asp)8-PEG-PCL. (Asp)8-PEG-PCL showed 11.07% loading
capacity and 95.91% encapsulation efficiency of curcumin. The curcumin-loaded
(Asp)8-PEG-PCL nanoparticles gave sustained release of curcumin in high dose for
>8 days. The curcumin-loaded (Asp)8-PEG-PCL nanoparticles showed strong
antitumorigenic effect on MG63, MCF7, and HeLa cancer cells. In conclusion,
(Asp)8-PEG-PCL nanoparticles were biocompatible, permeable in cells, a potent
carrier, and an efficient releaser of hydrophobic anticancer drug and were bone
specific. The curcumin-loaded (Asp)8-PEG-PCL nanoparticles showed strong
antitumorigenic ability in vitro. Therefore, (Asp)8-PEG-PCL nanoparticles could
be a potent carrier of hydrophobic anticancer drugs to treat the cancer
metastasized to bone.
PMID- 28507435
TI - Mesoporous silica nanoparticles trigger mitophagy in endothelial cells and
perturb neuronal network activity in a size- and time-dependent manner.
AB - PURPOSE: Mesoporous silica nanoparticles (MSNPs) are excellent candidates for
biomedical applications and drug delivery to different human body areas, the
brain included. Although toxicity at cellular level has been investigated, we are
still far from using MSNPs in the clinic, because the mechanisms involved in the
cellular responses activated by MSNPs have not yet been elucidated. MATERIALS AND
METHODS: This study used an in vitro multiparametric approach to clarify
relationships among size, dose, and time of exposure of MSNPs (0.05-1 mg/mL dose
range), and cellular responses by analyzing the morphology, viability, and
functionality of human vascular endothelial cells and neurons. RESULTS: The
results showed that 24 hours of exposure of endothelial cells to 250 nm MSNPs
exerted higher toxicity in terms of mitochondrial activity and membrane integrity
than 30 nm MSN at the same dose. This was due to induced cell autophagy (in
particular mitophagy), probably consequent to MSNP cellular uptake (>20%).
Interestingly, after 24 hours of treatment with 30 nm MSNPs, very low MSNP uptake
(<1%) and an increase in nitric oxide production (30%, P<0.01) were measured.
This suggests that MSNPs were able to affect endothelial functionality from
outside the cells. These differences could be attributed to the different protein
corona composition of the MSNPs used, as suggested by sodium dodecyl sulfate
polyacrylamide-gel electrophoresis analysis of the plasma proteins covering the
MSNP surface. Moreover, doses of MSNPs up to 0.25 mg/mL perturbed network
activity by increasing excitability, as detected by multielectrode-array
technology, without affecting neuronal cell viability. CONCLUSION: These results
suggest that MSNPs may be low-risk if prepared with a diameter <30 nm and if they
reach human tissues at doses <0.25 mg/mL. These important advances could help the
rational design of NPs intended for biomedical uses, demonstrating that careful
toxicity evaluation is necessary before using MSNPs in patients.
PMID- 28507438
TI - Pulmonary hypertension in Nigerian adults with sickle cell anemia.
AB - BACKGROUND: Sickle cell anemia (SCA) is the commonest hemoglobinopathy and is
associated with high morbidity and mortality. Pulmonary hypertension (PH) is
reported to play a significant role in this regard. There is very limited
literature on PH in SCA in Nigeria. OBJECTIVES: The objectives of this study were
to determine the prevalence of Doppler-derived PH in SCA, assess its influence on
exercise capacity, and determine the correlates and predictors of measures of
estimated pulmonary pressure. METHODS: A total of 92 SCA subjects had
echocardiography and 6-minute self-paced walking exercise. PH was diagnosed by
Doppler echocardiography on finding a tricuspid regurgitant velocity (TRV) of
>=2.5 m/s. The pulmonary flow profile was also assessed to estimate mean
pulmonary arterial pressure (MPAP). RESULTS: Doppler-derived PH was detected in
23.9% of adults with SCA. The 6-minute walking distance (6MWD) was significantly
lower in SCA adults with PH than in those without PH (380.33 +/- 63.17 m vs
474.28 +/- 76.74 m; p = 0.014). TRV and estimated MPAP had a significant inverse
correlation with the 6MWD (r = -0.442; p < 0.001 and r = -0.571; p < 0.001,
respectively). CONCLUSION: PH as derived by Doppler is common in Nigerian adults
with SCA and has a significantly negative influence on exercise capacity.
Screening for PH should be encouraged to optimize management and thus improve
their quality of life and life expectancy.
PMID- 28507440
TI - Ocular basal cell carcinoma: a brief literature review of clinical diagnosis and
treatment.
AB - Basal cell carcinoma (BCC) is a common malignant tumor throughout the world. One
of the known risk factors of BCC is intense exposure to ultraviolet radiation.
More than 50% of BCCs of the eyelid initially occur on the lower lid. The gold
standard of diagnosis of BCC is histopathology. Treatment options for BCC consist
of surgery, vismodegib, radiotherapy and imiquimod. Surgical excision using Mohs
micrographic surgery or wide surgical excision with frozen section margin control
is the first consideration for treatment of periocular BCC. Eyelid reconstruction
should be carefully considered as both function and esthetic outcome in patients
are important after clear excision of tumors. Exenteration is considered in the
case of extensive orbital invasion or high-risk aggressive tumors in order to
reduce the rate of recurrence.
PMID- 28507441
TI - Clinicopathological significance of p14ARF expression in lung cancer: a meta
analysis.
AB - BACKGROUND: p14ARF, a tumor suppressor protein, encoded by the p16 tumor
suppressor gene, has been reported to be associated with the clinicopathological
features of lung cancer. However, the evaluated outcomes were inconsistent and
remained inconclusive. In this study, we conducted a meta-analysis to clarify the
significance of p14ARF expression in lung cancer pathogenesis. MATERIALS AND
METHODS: Electronic databases, PubMed, Web of Knowledge, Embase, and CNKI, were
retrieved to collect relevant articles with inclusion and exclusion criteria.
Using Stata 12.0 software, 95% confidence intervals (CIs) and odds ratios (ORs)
were calculated. RESULTS: A total of 15 eligible case-control studies that
evaluated the relationship between p14ARF expression and lung cancer were
included in the meta-analysis. The results demonstrated that there were
significant associations between p14ARF expression and the risk of non-small-cell
lung cancer (NSCLC), lung adenocarcinoma, and lung squamous carcinoma (for NSCLC,
OR =11.02, 95% CI =5.30-22.92; for lung adenocarcinoma, OR =7.28, 95% CI =3.92
13.50; and for lung squamous carcinoma, OR =14.40, 95% CI =2.83-73.24). In the
stratified analysis based on race, significant associations between p14ARF
expression and lung cancer risk were found in Chinese population and Caucasians
(for Chinese population, OR = 7.02, 95% CI =4.48-11.00 and for Caucasians, OR
=4.19, 95% CI =1.42-12.38). Furthermore, the expression of p14ARF was
significantly associated with the TNM-stage of lung cancer in Chinese population
(OR =2.07, 95% CI =1.38-3.10). CONCLUSION: p14ARF expression was significantly
associated with the risk of lung cancer. In addition, the data of the meta
analysis showed that there was a significant correlation between p14ARF
expression and the TNM-stage of lung cancer in Chinese population.
PMID- 28507439
TI - Infrainguinal open reconstruction: a review of surgical considerations and
expected outcomes.
AB - Infrainguinal arterial occlusive disease can lead to potentially disabling and
limb-threatening conditions. Revascularization may be indicated for claudication,
rest pain, or tissue loss. Although endovascular interventions are becoming more
prevalent, open surgeries such as endarterectomy and bypass are still needed and
performed regularly. Open reconstruction has been associated with postoperative
morbidity, both at the local and at the systemic levels. Local complications
include surgical site infections (SSIs 0-5.3%), graft failure (12-60%), and
amputation (5.7-27%), and more systemic issues include cardiac (2.6-18.4%),
respiratory (2.5%), renal (4%), neurovascular (1.5%), and thromboembolic (0.2-1%)
complications. While such outcomes present an additional challenge to the
postoperative management of surgical patients, it may be possible to minimize
their occurrence through careful risk stratification and preoperative assessment.
Therefore, individualized selection of candidates for open repair requires
weighing the need for intervention against the likelihood of adverse outcomes
based on preoperative risk factors. This review provides an overview of open
reconstruction, focusing on identifying the clinical indications for surgery and
perioperative morbidity and mortality.
PMID- 28507443
TI - Erratum: Retinoic acid and arsenic trioxide in the treatment of acute
promyelocytic leukemia: current perspectives [Corrigendum].
AB - [This corrects the article on p. 1585 in vol. 10, PMID: 28352191.].
PMID- 28507442
TI - Aberrant promoter methylation profiles and association with survival in patients
with hepatocellular carcinoma.
AB - The aim of this study was to investigate the prognostic and diagnostic value of
genes with promoter methylation in hepatocellular carcinoma (HCC) patients. On
the basis of The Cancer Genome Atlas data, we identified genes with
differentially methylated promoters in HCC tissues and adjacent non-tumor
tissues, using the linear models for microarray data approach. Cox proportional
hazard regression analysis was applied to access the prognostic value of
identified differentially methylated genes. The diagnostic value of the genes was
evaluated through receiver operating characteristic. Pathway analyses were
performed to illustrate biological functions of the identified genes. Compared to
adjacent tissues, 77 genes with hypermethylated promoters and 2,412 genes with
hypomethylated promoters were identified in HCC. The promoter hypomethylations of
RNA5SP38, IL21, SDC4P, and MIR4439 were found to be associated with HCC patient
survival (P=0.035, 0.040, 0.004, and 0.024, respectively). Hypomethylated SDC4P
was associated with a better prognosis (hazard ratio, 0.482; 95% confidence
interval [CI], -0.147-1.110; P=0.007). The combination of the promoter
hypomethylations with RNA5SP38, IL21, and SDC4P showed an area under receiver
operating characteristic curves of 0.975 (95% CI, 0.962-0.989; P=4.811E-25).
Several pathways, including olfactory transduction, cytokine-cytokine receptor
interaction, natural killer cell-mediated cytotoxicity, as well as inflammation
mediated by chemokine and cytokine signaling pathway, were annotated with the
hypomethylated promoter genes. SDC4P promoter hypomethylation may be a potential
prognosis biomarker. A panel of promoter methylations in RNA5SP38, IL21, and
SDC4P was proven a novel approach to diagnosis HCC. The pathway analysis defined
the extensive functional role of DNA hypomethylation in cancer.
PMID- 28507444
TI - Antibodies against glutamic acid decarboxylase and indices of insulin resistance
and insulin secretion in nondiabetic adults: a cross-sectional study.
AB - BACKGROUND: Autoimmunity against insulin-producing beta cells from pancreatic
islets is a common phenomenon in type 1 diabetes and latent autoimmune diabetes
in adults. Some reports have also related beta-cell autoimmunity to insulin
resistance (IR) in type 2 diabetes. However, the extent to which autoimmunity
against components of beta cells is present and relates to IR and insulin
secretion in nondiabetic adults is uncertain. AIM: To explore the association
between antibodies against glutamic acid decarboxylase (GADA), a major antigen
from beta cells, and indices of whole-body IR and beta-cell capacity/insulin
secretion in adults who do not have diabetes. METHODS: We studied 81 adults of
both sexes aged 30-70, without known diabetes or any autoimmune disease.
Participants underwent an oral glucose tolerance test (OGTT) with determination
of plasma glucose and insulin at 0, 30, 60, 90, and 120 minutes. From these
results we calculated indices of insulin resistance (homeostasis model assessment
of insulin resistance [HOMA-IR] and incremental area under the insulin curve
[iAUCins]) and insulin secretion (corrected insulin response at 30 minutes and
HOMA beta-cell%). GADAs were measured in fasting plasma using immunoenzymatic
methods. RESULTS: We found an overall prevalence of GADA positivity of 21.3%,
without differences by sex and no correlation with age. GADA titers did not
change monotonically across quartiles of any of the IR or insulin secretion
indices studies. GADA did not correlate linearly with fasting IR expressed as
HOMA-IR (Spearman's r=-0.18, p=0.10) or postabsorptive IR expressed as iAUCins
(r=-0.15, p=0.18), but did show a trend toward a negative correlation with
insulin secretory capacity expressed by the HOMA-beta cell% index (r=-0.20,
p=0.07). Hemoglobin A1c, body mass index, and waist circumference were not
associated with GADA titers. CONCLUSION: GADA positivity is frequent and likely
related to impaired beta-cell function among adults without known diabetes.
PMID- 28507446
TI - Methotrexate: an effective monotherapy for refractory generalized morphea.
AB - INTRODUCTION: Morphea is an inflammatory skin disorder characterized by excessive
collagen deposition. Although treatment algorithms for morphea subtypes have been
suggested, no consistent recommendations are available. This study attempts to
evaluate the clinical efficacy of methotrexate (MTX) as monotherapy in refractory
generalized morphea. METHODS: It is a retrospective study, including 20 patients
who had already been treated with various topical and systemic therapies with
minimal clinical improvement. Patients received orally MTX at a of dosage 15 mg
once weekly. Duration of the use, dosage of MTX, and adverse events were
recorded. Clinical assessment of skin lesions was performed and documented.
RESULTS: The mean disease duration was 27 months before the initiation of MTX
treatment. After 12 months of therapy, very good response was achieved in 6
patients (30%), good response in 10 patients (50%), and fair response in 2
patients (10%), while 2 patients (10%) had failed treatment. Patients were
followed up for a mean time interval of 21 months. No serious adverse event was
recorded. CONCLUSION: MTX has been already proved to be an effective and well
tolerated treatment in pediatric patients with morphea. The majority of the group
of adult patients showed very good and good improvement when treated with MTX.
Although this is an uncontrolled study, MTX monotherapy was considered a safe and
effective treatment for the management of this specific clinical subset of
morphea in adults.
PMID- 28507445
TI - Evaluation of fatigue and its correlation with quality of life index, anxiety
symptoms, depression and activity of disease in patients with psoriatic
arthritis.
AB - BACKGROUND: Psoriatic arthritis is associated with psychosocial morbidity and
decrease in quality of life. Psychiatric comorbidity also plays an important role
in the impairment of quality of life and onset of fatigue. OBJECTIVES: This study
aimed to assess the prevalence of fatigue in psoriatic arthritis patients and to
correlate it to quality of life indexes, functional capacity, anxiety, depression
and disease activity. PATIENTS AND METHODS: This cross-sectional study was
performed on outpatients with psoriatic arthritis. Functional Assessment of
Chronic Illness Therapy - Fatigue (FACIT-F; version 4) was used to measure
fatigue; 36-Item Short Form Health Survey (SF-36) and Psoriasis Disability Index
(PDI) to measure quality of life; Health Assessment Questionnaire (HAQ) to assess
functional capacity; Hospital Anxiety and Depression (HAD) scale to measure
anxiety and depression symptoms; Psoriasis Area and Severity Index (PASI), Bath
Ankylosing Spondylitis Disease Activity Index (BASDAI) and Clinical Disease
Activity Index (CDAI) to evaluate clinical activity. RESULTS: In all, 101
patients with mean age of 50.77 years were included. The mean PDI score was 8.01;
PASI score, 9.88; BASDAI score, 3.59; HAQ score, 0.85; HAD - Anxiety (HAD A)
score, 7.39; HAD Depression (HAD D) score, 5.93; FACIT-Fatigue Scale (FACIT-FS)
score, 38.3 and CDAI score, 2.65. FACIT-FS was statistically associated with PASI
(rs -0.345, p<0.001), PDI (rs -0.299, p<0.002), HAQ (rs -0.460, p<0.001), HAD A
(rs -0.306, p=0.002) and HAD D (rs -0.339, p<0.001). The correlations with CDAI
and BASDAI were not confirmed. There was statistically significant correlation
with all of the domains of SF-36 and FACIT-F (version 4). CONCLUSION: Prevalence
of fatigue was moderate to intense in <25% of patients with psoriatic arthritis.
Fatigue seems to be more related to the emotional and social aspects of the
disease than to joint inflammatory aspects, confirming that the disease's
visibility is the most disturbing aspect for the patient and that "skin pain" is
more intense than the joint pain.
PMID- 28507447
TI - Managing refractory cryoglobulinemic vasculitis: challenges and solutions.
AB - Cryoglobulinemia is thought to be a rare condition. It may be an isolated
disorder or secondary to a particular disease. According to immunoglobulin
composition, cryoglobulinemia is classified into three types. In mixed
cryoglobulinemia (types II and III), vascular deposition of cryoglobulin
containing immune complexes and complement may induce a clinical syndrome,
characterized by systemic vasculitis and inflammation - cryoglobulinemic
vasculitis (CryoVas). Most common clinical manifestations in CryoVas are skin
lesions (orthostatic purpura and ulcers), weakness, peripheral neuropathy,
Raynaud's phenomenon, sicca syndrome, membranoproliferative glomerulonephritis,
and arthralgia and seldom arthritis. In patients with mixed cryoglobulinemia,
prevalence of anti-hepatitis C virus (HCV) antibodies and/or HCV RNA, detected by
polymerase chain reaction (PCR), is reported to be up to 90%, indicating a
significant role of HCV in the development of this condition. The goals of
therapy for mixed cryoglobulinemia include immunoglobulin level reduction and
antigen elimination. CryoVas not associated with HCV infection should be treated
according to treatment recommendations for small-vessel vasculitides. CryoVas
associated with chronic HCV infection should be treated with antivirals along
with immunosuppressive drugs, with or without plasmapheresis, depending on
disease severity and organ involvement. Patients who do not respond to first-line
therapy may achieve remission when treatment with rituximab is started as second
line therapy. In HCV-related CryoVas, antiviral therapy should be given along
with rituximab in order to achieve complete or partial remission. Moreover,
rituximab has proven to be a glucocorticoid-sparing medication. Other potential
therapies for refractory CryoVas include mycophenolate mofetil and belimumab,
while tumor necrosis factor (TNF) inhibitors are not effective.
PMID- 28507448
TI - Thiopurine S-methyltransferase polymorphisms in acute lymphoblastic leukemia,
inflammatory bowel disease and autoimmune disorders: influence on treatment
response.
AB - The thiopurine S-methyltransferase (TPMT) gene encodes for the TPMT enzyme that
plays a crucial role in the metabolism of thiopurine drugs. Genetic polymorphisms
in this gene can affect the activity of the TPMT enzyme and have been correlated
with variability in response to treatment with thiopurines. Advances in the
pharmacogenetics of TPMT allowed the development of dosing recommendations and
treatment strategies to optimize and individualize prescribing thiopurine in an
attempt to enhance treatment efficacy while minimizing toxicity. The influence of
genetic polymorphisms in the TPMT gene on clinical outcome has been well
documented and replicated in many studies. In this review, we provide an overview
of the evolution, results, conclusions and recommendations of selected studies
that investigated the influence of TPMT pharmacogenetics on thiopurine treatment
in acute lymphoblastic leukemia, inflammatory bowel disease and autoimmune
disorders. We focus mainly on prospective studies that explored the impact of
individualized TPMT-based dosing of thiopurines on clinical response. Together,
these studies demonstrate the importance of preemptive TPMT genetic screening and
subsequent dose adjustment in mitigating the toxicity associated with thiopurine
treatment while maintaining treatment efficacy and favorable long-term outcomes.
In addition, we briefly address the cost-effectiveness of this pharmacogenetics
approach and its impact on clinical practice as well as the importance of recent
breakthrough advances in sequencing and genotyping techniques in refining the
TPMT genetic screening process.
PMID- 28507450
TI - Patient safety attitudes of pharmacy students in an Ethiopian university: a cross
sectional study.
AB - INTRODUCTION: Patient safety is a major health care concern and is being included
in an undergraduate curriculum as it plays a major role in lessening harm.
Therefore, we aim to assess the attitude of pharmacy students toward patient
safety. METHODS: A cross-sectional study using a self-administered questionnaire
containing 21 items was conducted at the University of Gondar among fourth and
fifth year students. Data analysis was performed to calculate mean, standard
deviation, percentages, and logistic regressions using SPSS software version 22
(IBM Corporation, Armonk, NY, USA). Statistical significance was set at P<0.05.
RESULTS: A total of 83 pharmacy students (fourth year groups=50, fifth year
groups=33) participated in the study with response rate of 92%. Majority of the
students 70/83 (84.33%) had the overall positive attitude of patient safety. Most
of the respondents (80.7%) agree or strongly agree that after an error occurs, an
effective strategy is to work hard to be more careful. Most of them (79.6%)
believe that pharmacists should routinely spend part of their professional time
working to improve patient care. About half (48.2%) of pharmacy students disagree
or strongly disagree that pharmacists should discuss and report errors to an
affected patient and their family even if the patient is not harmed. No
significant association between the attitude of pharmacy students toward patient
safety and their age, sex and year of study was found. CONCLUSION: Pharmacy
students have the overall good attitude to patient safety. However, they claimed
the culture and attitude within the pharmacy workplace lacked for patient safety.
Moreover, standardized patient safety course should be considered in the
curriculum for junior pharmacy students to improve their attitude toward patient
safety.
PMID- 28507449
TI - Perirenal fat stranding is not a powerful diagnostic tool for acute
pyelonephritis.
AB - PURPOSE: Pyelonephritis, an upper urinary tract infection, is a serious infection
that often requires hospitalization. However, the accurate diagnosis of acute
pyelonephritis can be difficult, especially among older individuals who can
present with unusual symptoms. Imaging with computed tomography (CT) is not
unusual in the diagnosis of pyelonephritis, with some clinicians regarding
perirenal fat stranding (PFS) as a characteristic finding. However, the
sensitivity and specificity of PFS in diagnosing pyelonephritis are currently
unknown. We therefore sought to clarify the relevance of PFS in diagnosing acute
pyelonephritis. PATIENTS AND METHODS: We conducted a case-controlled
retrospective analysis of medical records. The pyelonephritis group included 89
patients who had been diagnosed with acute pyelonephritis, while the control
group included 319 patients who had undergone percutaneous renal biopsy. CT
findings were available for both groups. The frequency of PFS and its sensitivity
and specificity for the diagnosis of acute pyelonephritis were investigated.
RESULTS: The mean ages of the pyelonephritis and control groups were 74+/-15
years and 63+/-16 years, respectively. A total of 28% of men were in the
pyelonephritis group vs 61% of men in the control group. The frequency of PFS was
72% in the pyelonephritis group vs 39% in the control group. Age and renal
dysfunction were associated with an increased frequency of PFS. After adjusting
for age, sex, and renal function using a propensity score analysis, the
sensitivity, specificity, and positive likelihood ratio of PFS for diagnosing
acute pyelonephritis were 72%, 58%, and 1.7, respectively. CONCLUSION: The
presence of PFS was not useful in diagnosing acute pyelonephritis.
PMID- 28507452
TI - Consulted ethical problems of clinical nursing practice: perspective of faculty
members in Japan.
AB - BACKGROUND: There are several studies that have targeted student nurses, but few
have clarified the details pertaining to the specific ethical problems in
clinical practice with the viewpoint of the nursing faculty. This study was to
investigate the ethical problems in clinical practice reported by student nurses
to Japanese nursing faculty members for the purpose of improving ethics education
in clinical practice. METHOD: The subjects comprised 705 nursing faculty members
(we sent three questionnaires to one university) who managed clinical practice
education at 235 Japanese nursing universities. We performed a simple tabulation
of the four items shown in the study design. 1) the details of student nurse
consultations regarding ethics in clinical practice (involving the students
themselves, nurses, care workers, clinical instructors, and nursing faculty
members); 2) the methods of ethics education in clinical practice; 3) the
difficulties experienced by the nursing faculty members who received the
consultations; and 4) the relationship between clinical practice and lectures on
ethics. Furthermore, the analysis was based on the idea of ethical principles,
respect for persons, beneficence, and justice. RESULTS: The response rate was 28%
(198 questionnaires). The nursing faculty members were consulted for various
problems by student nurses. The details of these consultations were characterized
by the principles of respect for patient by nurses, the principles of benevolence
by faculty and clinical instructors, and the principle of justice pertaining to
evaluations. The results indicate that there is an awareness among the nursing
faculty regarding the necessity of some sort of ethics education at clinical
settings. Moreover, based on the nature of the contents of the consultations
regarding the hospital and staff, it was evident that the nursing faculty
struggled in providing responses. More than half of subjects exhibited an
awareness of the relationship between the classroom lectures on ethics and
clinical practice. CONCLUSION: The results suggest the need for analyzing the
ethical viewpoints of student nurses, prior learning, and collaboration with
related courses as part of ethics education in clinical practice.
PMID- 28507453
TI - Erratum to: Suppression of Spry4 enhances cancer stem cell properties of human
MDA-MB-231 breast carcinoma cells.
AB - [This corrects the article DOI: 10.1186/s12935-016-0292-7.].
PMID- 28507454
TI - Hypoxia and TGF-beta1 induced PLOD2 expression improve the migration and invasion
of cervical cancer cells by promoting epithelial-to-mesenchymal transition (EMT)
and focal adhesion formation.
AB - BACKGROUND: Intra-tumoral hypoxia and increases in extracellular level of
transforming growth factor beta1 (TGF-beta1), which are common findings in
cancer, are associated with an increased risk of metastasis and mortality.
Moreover, metastasis is the leading cause of death of patients with cervical
cancer. PLOD2 is an intracellular enzyme required for the biogenesis of collagen
and its expression can be induced by hypoxia and TGF-beta1. Specifically, PLOD2
is up-regulated in several types of cancer, including cervical cancer, and is
associated with cancer metastasis. Thus, in this research, we aimed to
investigate the role of PLOD2 in the motility of cervical cancer cells and to
show the molecular mechanism underlying this effect. METHODS: siRNA was used to
knockdown PLOD2 in the cervical cancer cell lines HeLa and SiHa. The ability of
cells to migrate and invade, their adhesion to type I collagen, and their
capacity for epithelial-to-mesenchymal transition (EpsilonMUTau) and focal
adhesion formation were analyzed. Gene expression changes were validated by qRT
PCR, Western blotting and Immunocytochemistry. The morphological status of cells
was examined using phalloidin staining. Differences in PLOD2 expression among
patients with cervical cancer were identified by referring to public databases,
including Oncomine and TCGA. RESULTS: Hypoxia and TGF-beta1 enhanced the
expression of PLOD2 in HeLa and SiHa cells, and knockdown of PLOD2 inhibited cell
motility and EMT. Moreover, the depletion of PLOD2 attenuated hypoxia-mediated
cell migration and invasion and inhibited TGF-beta1-induced phenotypic EMT-like
changes by preventing beta-catenin from entering the nucleus. In addition, PLOD2
depletion decreased cell adhesion to extracellular collagen by inhibiting the
formation of focal adhesions. Moreover, a database analysis showed that PLOD2
expression is associated with human cervical cancer progression. CONCLUSIONS:
Overall, our results indicated that hypoxia- and TGF-beta1-induced PLOD2
expression promotes the migratory, invasive and adhesive capacities of cervical
cancer cells by participating in TGF-beta1 induced EMT and the formation of focal
adhesions.
PMID- 28507455
TI - Neoadjuvant chemoradiotherapy of the rectal carcinoma - The correlation between
the findings on the restaging multiparametric 3T MRI scanning and the surgical
findings.
AB - AIM: To figure out how to correlate the findings on functional MRI and carried
out after neoadjuvant CRT of rectal carcinoma with final histology after surgery.
BACKGROUND: Neoadjuvant CRT is the standard treatment of locally advanced rectal
carcinoma. Its use leads to the downstaging of the disease and in 15-42% of
patients even to the detection of pCR after TME. The use of functional MRI
improves the sensitivity and specificity of pCR detection up to 52-64% and 89
98%, respectively. MATERIALS AND METHODS: Between January 2013 and June 2016, 67
patients suffering from histologically proven locally advanced rectal cancer
underwent neoadjuvant RT or CRT. We selected for further investigation only
patients (33 patients) who underwent pelvic staging and restaging using
multiparametric imaging on 3T MRI scanner. We compared the findings on functional
MRI after neoadjuvant CRT with final histology after surgery. RESULTS: In 15
patients pathologic staging of primary tumor differed from expected staging
assessed according to preoperative MRI. In 5 patients pathologic complete
remission was achieved. In none of these 5 patients pCR was predicted using
preoperative MRI. Sensitivity and specificity of MRI in predicting pCR were 0%
and 96%. Accuracy of MRI in predicting pT and pN was 79% and 74%. CONCLUSIONS: We
have verified that the use of neoadjuvant CRT in the treatment of locally
advanced rectal carcinoma leads to a possible achievement of pCR. But in our
group of patients this was not predictable nor was it with the use of
multiparametric 3T MRI.
PMID- 28507458
TI - Effect of tumor amplitude and frequency on 4D modeling of Vero4DRT system.
AB - BACKGROUND: An important issue in indirect dynamic tumor tracking with the
Vero4DRT system is the accuracy of the model predictions of the internal target
position based on surrogate infrared (IR) marker measurement. We investigated the
predictive uncertainty of 4D modeling using an external IR marker, focusing on
the effect of the target and surrogate amplitudes and periods. METHODS: A
programmable respiratory motion table was used to simulate breathing induced
organ motion. Sinusoidal motion sequences were produced by a dynamic phantom with
different amplitudes and periods. To investigate the 4D modeling error, the
following amplitudes (peak-to-peak: 10-40 mm) and periods (2-8 s) were
considered. The 95th percentile 4D modeling error (4D-E95%) between the detected
and predicted target position (MU + 2SD) was calculated to investigate the 4D
modeling error. RESULTS: 4D-E95% was linearly related to the target motion
amplitude with a coefficient of determination R2 = 0.99 and ranged from 0.21 to
0.88 mm. The 4D modeling error ranged from 1.49 to 0.14 mm and gradually
decreased with increasing target motion period. CONCLUSIONS: We analyzed the
predictive error in 4D modeling and the error due to the amplitude and period of
target. 4D modeling error substantially increased with increasing amplitude and
decreasing period of the target motion.
PMID- 28507456
TI - Adjuvant intraoperative radiotherapy for selected breast cancers in previously
irradiated women: Evidence for excellent feasibility and favorable outcomes.
AB - BACKGROUND: The present report provides preliminary outcomes with intraoperative
radiotherapy delivered to women with breast cancer included in a re-irradiation
program. MATERIALS AND METHODS: From October 2010 to April 2014, thirty women
were included in a re-irradiation protocol by exploiting IORT technique. The
median time between the two irradiations was 10 years (range 3-50). All patients
underwent conservative surgery, sentinel lymph node excision and IORT with
electron beam delivered by a mobile linear accelerator. Primary endpoint was
esthetic result and consequential/late toxicity; secondary endpoints were local
control (LC), disease free survival (DFS) and overall survival (OS). RESULTS:
With a median follow up of 47 months (range 10-78), we analyzed 29 patients (1
lost at follow up). Twenty-seven patients (90%) had presented breast cancer local
relapse or a new primary cancer in the same breast after a previous conservative
surgery plus radiation treatment; three patients (10%) had previously received
irradiation with mantle field for Hodgkin Lymphoma. Esthetic result was excellent
in 3 pts (10%), good in 12 pts (41%), fair in 8 pts (28%) and poor in 6 pts
(21%). 12 (41%) patients showed subcutaneous fibrosis at the last follow-up. LC,
DFS and OS at five years was 92.3%, 86.3% and 91.2%, respectively. CONCLUSION:
Although we analyzed a small number of patients, our results are satisfactory and
this approach is feasible even if it could not be considered the standard
treatment. Further clinical trials exploring IORT are needed to identify possible
subgroups of patients that might be suitable for this type of approach.
PMID- 28507457
TI - Evaluating the performance of TG-43 protocol in esophageal HDR brachytherapy
viewpoint to trachea inhomogeneity.
AB - AIM: The aim of this study is to evaluate the effect of air within trachea on
dose calculations of esophageal HDR brachytherapy treatment planning. BACKGROUND:
Dose calculations in esophageal HDR brachytherapy treatment planning systems are
greatly based on TG-43 protocol which in all materials are considered to be water
equivalent. MATERIALS AND METHODS: A cylindrical PMMA phantom with a tube in the
center (neck equivalent phantom) accompanied by Flexitron HDR brachytherapy
system was used in this study. Brachytherapy applicators with various diameters
were placed inside the esophageal tube and EDR2 film was used for dosimetry. The
absorbed dose by reference point of esophageal HDR brachytherapy and anterior
wall of trachea were measured and compared with those calculated by Flexiplan
treatment planning system. RESULTS: Based on the performed statistical analysis
(t-test) with 95% confidence level (t-value >1.96), there was a meaningful
difference between the results of film dosimetry and treatment planning at all of
the points understudy. CONCLUSION: The meaningful difference between the results
of film dosimetry and treatment planning indicates that the trachea inhomogeneity
has a considerable effect on dose calculations of Flexiplan treatment planning
software featuring the TG-43 dose calculation algorithm. This mismatch can affect
the accuracy of performed treatment plan and irradiation.
PMID- 28507459
TI - Spironolactone ameliorates the cardiovascular toxicity induced by concomitant
trastuzumab and thoracic radiotherapy.
AB - AIM: We aimed to evaluate impact of spironolactone (S) on cardiovascular toxicity
of concomitant use of radiotherapy (RT) and trastuzumab (T). BACKGROUND: S, an
aldosterone receptor antagonist, is known to ameliorate the cardiac damage. S
ameliorates anthracycline -induced cardiotoxicity, there is no data regarding to
effect of S on both T and radiation-induced cardiotoxicity. MATERIALS/METHODS:
Eighty rats were divided into eight groups: group (G) 1 was defined as control
group. G2, G3 and G4 were RT, S and T groups respectively. G5, G6, G7 and G8 were
RT + T, T + S, RT + S and RT + T + S groups respectively. Rats were sacrificed at
6th hour; 21st and 100th days after RT. Heart and thoracic aorta samples were
taken for microscopical examination. RESULTS: Cardiac inflammation and fibrosis
scores and; TGF-beta expression were not significantly different within study
groups at 6th hour and 21st days of RT. By 100th days of RT fibrosis scores and
TGF-beta expression in cardiac samples were significantly different between study
groups (p values were 0.004 and 0.002 respectively). Pair-wise comparisons
revealed that both cardiac fibrosis scores and TGF-beta expression levels were
higher in G5 when compared to G8 (p values were 0.046 and 0.028 respectively).
Moreover the TGF-beta expression was higher in G5 when compared to G2 (p =
0.046). We could not demonstrate any significant differences with respect to
inflammation, fibrosis and TGF-beta expression in thoracic aorta samples between
study groups. CONCLUSIONS: Although S had a protective effect on cardiac tissue
it had no protective effect on thoracic aorta when administered with RT + T.
PMID- 28507460
TI - Validation of the liver mean dose in terms of the biological effective dose for
the prevention of radiation-induced liver damage.
AB - AIM: The purpose of this study was to determine the optimal mean liver
biologically effective dose (BED) to prevent radiation-induced liver disease
(RILD) in stereotactic body radiation therapy (SBRT). BACKGROUND: The actual mean
doses appropriate for liver irradiation in modern radiotherapy techniques have
not been adequately investigated, although SBRT is sometimes alternatively
performed using fractionated regimens. MATERIALS AND METHODS: SBRT treatment
plans for liver tumors in 50 patients were analyzed. All distributions of the
physical doses were transformed to BED2 using the linear-quadratic model. The
relationship between physical doses and the BED2 for the liver were then
analyzed, as was the relationship between the mean BED2 for the liver and the
planning target volume (PTV). RESULTS: A significantly positive correlation was
observed between the mean physical dose for the background liver and the mean
BED2 for the whole liver (P < 0.0001, r = 0.9558). Using the LQ model, a mean
BED2 of 73 and 16 Gy for the whole liver corresponded to the hepatic tolerable
mean physical dose of 21 and 6 Gy for Child-Pugh A- and B-classified patients,
respectively. Additionally, the PTV values were positively correlated with the
BEDs for the whole liver (P < 0.0001, r = 0.8600), and the background liver (P <
0.0001, r = 0.7854). CONCLUSION: A mean BED2 of 73 and 16 Gy for the whole liver
appeared appropriate to prevent RILD in patients with Child-Pugh classes A and B,
respectively. The mean BED2 for the liver correlated well with the PTV.
PMID- 28507461
TI - Washed Away; How Not to Lose Your RNA during Isolation.
AB - Cryptosporidium oocysts have extremely robust walls that protect the parasite
against environmental pressures. Analyses must be sensitive to detect the few
organisms (if any) present in environmental samples. After a series of negative
nucleic acid amplification results on spiked samples, following a standard RNA
isolation protocol, it seemed probable that oocyst RNA had been lost in the
washing steps of the isolation protocol. By reducing both the volume of wash
buffer and the number of washing steps, positive results could be re-established.
Insufficient washing, however, seemed to prevent downstream analysis, probably
because of inhibitory substances remaining in the RNA isolate. Nucleic acid
isolation protocols for low numbers of "difficult" organisms should be adapted,
according to the material to optimize the balance between removal of inhibitors
and retention of target, thereby improving the performance of the technique.
PMID- 28507462
TI - Comparative Analysis of Non-viral Transfection Methods in Mouse Embryonic
Fibroblast Cells.
AB - Mouse embryonic fibroblast (MEF) cells are an important in vitro model for
developmental biology, disease, and reprogramming studies. However, as with other
primary cells, they are challenging to transfect. Although viral gene-delivery
methods achieve high gene-delivery efficiency, challenges with cell mutagenesis
and safety among others have led to the use and improvement of non-viral gene
delivery methods in MEF cells. Despite the importance of gene delivery in MEF
cells, there is limited comparison of method/reagent efficacy. In this study, we
compared the effectiveness of different gene-delivery methods and several
reagents currently available in MEF cells by introducing a plasmid containing
enhanced green fluorescent protein (EGFP). We analyze transfection efficiency by
EGFP fluorescence. Our results suggest that two gene-delivery methods
electroporation and magnetofection in combination with a lipid reagent, are the
most efficient transfection methods in MEF cells. This study provides a
foundation for the selection of transfection methods or reagents when using MEF
cells.
PMID- 28507464
TI - Chemical composition and biological activities of Salvia officinalis essential
oil from Tunisia.
AB - The aim of this study is to evaluate the chemical composition, antioxidant,
antimicrobial, insecticidal and allelopathic activities of Tunisia Salvia
officinalis essential oil (SoEO). The SoEO was characterized by the presence of
49 components with camphor (25.14 %), alpha-thujone (18.83 %), 1,8-cineole (14.14
%), viridiflorol (7.98 %), beta-thujone (4.46 %) and beta-caryophyllene (3.30 %)
as the major components, determined by gas chromatography-mass spectrometry. The
level of antioxidant activity, determined by complementary tests, namely 2,2
diphenyl-1-picrylhydrazyl radical-scavenging (IC50= 6.7 mg/mL), linoleic acid
peroxidation (IC50= 9.6 mg/mL) and ferric reducing assays (IC50= 28.4 mg/mL), was
relatively moderate. The SoEO was also screened for its antimicrobial activity.
Good to moderate inhibitions were recorded for most of tested microorganisms. It
also exhibited important insecticidal activity against Spodoptera littoralis
larvae and Tribolium castaneum adults with LC50 values of 55.99 and 97.43 ul/L
air, respectively. The effect of the SoEO on seeds germination and growth showed
different activities against radical and hypocotyl elongation of the tested
species. These results suggest the potential use of the SoEO as natural
antimicrobial preservative in cosmetic, pharmaceutical industry and in pest
management.
PMID- 28507463
TI - Radiotherapy-Induced Skin Reactions Induce Fibrosis Mediated by TGF-beta1
Cytokine.
AB - PURPOSE: This study aimed to investigate radiation-induced lesions on the skin in
an experimental animal model. Methods and Materials: Cutaneous wounds were
induced in Wistar rats by 4 MeV energy electron beam irradiation, using a dose
rate of 240 cGy/min, for 3 different doses (10 Gy, 40 Gy, and 60 Gy). The skin
was observed 5, 10, and 25 days (D) after ionizing radiation exposition. RESULTS:
Infiltrate inflammatory process was observed in D5 and D10, for the 40 Gy and 60
Gy groups, and a progressive increase of transforming growth factor beta1 is
associated with this process. It could also be noted a mischaracterization of
collagen fibers at the high-dose groups. CONCLUSION: It was observed that the
lesions caused by ionizing radiation in rats were very similar to radiodermatitis
in patients under radiotherapy treatment. ADVANCES IN KNOWLEDGE: This study is
important to develop strategies to prevent radiation-induced skin reactions.
PMID- 28507466
TI - High level of miR-196b at newly diagnosed pediatric acute myeloid leukemia
predicts a poor outcome.
AB - Differential expression of microRNAs (miRNAs) has been implicated in
leukemogenesis. We investigate the expression pattern of miR-196b. Using
quantitative real-time PCR (qRT-PCR), we detected the expression of miR-196b and
its correlated genes (SMC1A/MLH1) in initial pediatric AML. A significant
association was observed between overexpression of miR-196b and inferior overall
survival of pediatric AML (Log Rank P<0.0001). AML M4/5 subtype, high white blood
cell (WBC) count at presentation, MLL rearrangement, or FLT3-ITD mutation at
diagnosis and non-remission group after the first induction chemotherapy
possessed higher miR-196b expression. Furthermore, a positive relationship was
found between the expression of miR-196b and SMC1A/MLH1 (Spearman's r=0.37 and
0.44, P=0.001 and <0.0001, respectively). Taken together, these findings suggest
that differentially high expression of miR-196b in diagnostic marrow samples of
pediatric AML is associated with unfavorable outcome, and miR-196b potentially
can be a novel biomarker for the diagnosis, prognosis and treatment in pediatric
AML.
PMID- 28507467
TI - Preparation and characterization of beta-glucan particles containing a payload of
nanoembedded rifabutin for enhanced targeted delivery to macrophages.
AB - beta-glucan particles (GP) are polymeric carbohydrates, mainly found as
components of cell wall fungi, yeast, bacteria and also in cereals such as barley
and oat, and have been recently shown to have application in macrophage-targeted
drug delivery. The aim of this study was to prepare and characterize GP
containing a large payload of Rifabutin (RB), an anti-tuberculosis drug effective
against MDR-TB at lower MIC than Rifampicin. GP were prepared from yeast cells by
acidic and alkaline extraction were either spray dried or lyophilized, prior to
RB loading and alginate sealing. The FTIR and 13C-NMR spectra of the GP confirmed
a beta-(1->3) linked glucan structure, with a triple-helical conformation. The
spray dried GP exhibited better characteristics in terms of uniformity, size
range (2.9 to 6.1 um) and more than 75 % particles were below 3.5 MUm. The RP
HPLC analysis of spray dried GP revealed drug entrapment and drug loading up to
81.46 +/- 4.9 % and ~40.5 +/- 1.9 %, respectively, as compared to those dried by
lyophilization. Electron microscopy showed nearly spherical and porous nature of
GP, and the presence of drug 'nanoprecipitates' filling the pore spaces. The
formulation showed adequate thermal stability for pharmaceutical application. The
particles were readily phagocytosed by macrophage(s) within 5 min of exposure.
Drug release occurred in a sustained manner via diffusion, as the release
kinetics best fit for drug release was obtained using Higuchi's equation. Thus,
the spray dried GP-based-formulation technology holds promise for enhanced
targeted delivery of anti-TB drug(s) to macrophage within a therapeutic window
for the clearance of intracellular bacteria.
PMID- 28507468
TI - Paradoxical effect of minocycline on established neuropathic pain in rat.
AB - Neuropathic pain occurs after peripheral nerve damage, inflammation or infection.
In this situation, microglial cells become activated and play a key role in
producing pain. Minocycline (microglia inhibitor), was reported to reduce pain
when used preventively. However, it seems that, when used after nerve injury,
results in its pain reducing effects are different. In this regard, to assess the
pain reducing differences of minocycline, neuropathic pain was induced by the
ligation of the sciatic nerve in the rat which is recognized as chronic
constriction injury (CCI) and minocycline was administered before and after
sciatic nerve injury. Wistar male rats (200-250 g, n=6) were used in these
experiments. Rats were distributed in various groups: vehicle-treated CCI
(control), sham-operated and minocycline-treated CCI groups. In the first part of
the experiment (pre-injury study), minocycline (10, 20, 30 and 40 mg/kg,) was
injected one hour before surgery and then daily for two weeks. In the second part
(post injury study), minocycline was administered: 1: at day one after nerve
damage once a day to day 14, 2: at day seven after surgery and continued daily
until day 14. Analgesimeter for thermal hyperalgesia and von Frey hairs for
mechanical allodynia were used to evaluate pain behavior. Thermal hyperalgesia
and mechanical allodynia were attenuated significantly, when minocycline used
before surgery, while it was not able to reduce pain behavior administered after
surgery. It seems that, in spite of what some previous studies have reported,
here, minocycline is not able to attenuate established neuropathic pain.
PMID- 28507465
TI - Distribution of polymorphic variants of CYP2A6 and their involvement in nicotine
addiction.
AB - Tobacco consumption has become a major public health issue, which has motivated
studies to identify and understand the biological processes involved in the
smoking behavior for prevention and smoking cessation treatments. CYP2A6 has been
identified as the main gene that codifies the enzyme that metabolizes nicotine.
Many alleles have been identified after the discovery of CYP2A6, suggesting a
wide interethnic variability and a diverse smoking behavior of the allele
carrying individuals. The main purpose of this review is to update and highlight
the effects of the CYP2A6 gene variability related to tobacco consumption
reported from diverse human populations. The review further aims to consider
CYP2A6 in future studies as a possible genetic marker for the prevention and
treatment of nicotine addiction. Therefore, we analyzed several population
studies and their importance at addressing and characterizing a population using
specific parameters. Our efforts may contribute to a personalized system for
detecting, preventing and treating populations at a higher risk of smoking to
avoid diseases related to tobacco consumption.
PMID- 28507469
TI - Lungs deposition and pharmacokinetic study of submicron budesonide particles in
Wistar rats intended for immediate effect in asthma.
AB - The purpose of the present investigation was to study the aerosolization, lungs
deposition and pharmacokinetic study of inhalable submicron particles of
budesonide in male Wistar rats. Submicron particles were prepared by antisolvent
nanoprecipitation method and freeze-dried to obtain free flowing powder. The
freeze-drying process yielded dry powder with desirable aerodynamic properties
for inhalation therapy. An in-house model inhaler was designed to deliver
medicine to lungs, optimized at dose level of 10 mg for 30 sec of fluidization.
The in vitro aerosolization study demonstrates that submicron particles dissolve
faster with improved aerosolization effect as compared to micronized budesonide.
Both submicron and micron particles were compared for in vivo lungs deposition.
The results showed that relatively high quantity of submicron particles reaches
deep into the lungs as compared to micron particles. Most pronounced effect
observed with submicron particles from pharmacokinetic parameters was the
enhancement in peak plasma concentration (Cmax) by 28.85 %, and increase in area
under concentration curve (AUC0-8h) by 30.33 % compared to micron sized
particles. The results suggested that developed submicronized formulation of
budesonide can be used for pulmonary drug delivery for high deposition to deep
lungs tissues.
PMID- 28507470
TI - Evaluating the relationship of blood pressure, plasma angiotensin peptides and
aldosterone with cognitive functions in patients with hypertension.
AB - Renin Angiotensin Aldosterone System (RAAS) plays an important role in the
development of hypertension. On the other hand, hypertension is a well-known and
independent risk factor for cognitive impairment. The aim of the present study
was to evaluate the relationship of blood pressure control, plasma angiotensin
peptides and aldosterone with cognitive functions. Forty-one patients who were
under treatment with the same antihypertensive medications for at least three
months were included in the study. Plasma angiotensin II, angiotensin 1-7,
angiotensin IV, and aldosterone concentrations were analyzed using an enzyme
linked immunosorbent assay (ELISA). Standardized Mini Mental State Examination
(SMMSE) was used to evaluate cognitive functions. When the participants were
grouped according to their SMMSE scores (cut-off value: 26 points), we determined
significant differences between systolic blood pressure (SBP) levels, diastolic
blood pressure levels, plasma angiotensin II and angiotensin 1-7 concentrations
of the groups. When the participants were stratified according to their SBP
levels (cut-off value: 140 mm Hg), we found significant differences in SMMSE
scores and plasma angiotensin IV concentrations of the groups. A negative
correlation between SBP and SMMSE scores and strong linear correlations among
angiotensin peptides levels were determined. The relationship found between SBP
and SMMSE in the present study was compatible with the literature. Our 33
patients were using at least one angiotensin II receptor blocker (ARB). Regarding
AT1 receptor blockage, the significant association between higher SMMSE scores
and increased angiotensin peptides may support a finding that ARBs prevent
dementia and improve cognitive function. Further larger studies are needed to
confirm and prove the relation of RAAS biochemical parameters with cognitive
function.
PMID- 28507471
TI - Seroepidemiological study of Toxoplasma gondii infection in a population of
Iranian epileptic patients.
AB - Epilepsy is one of the most common neurologic disorders. Underlying cause of
epilepsy is unknown in 60 % of the patients. Toxoplasma gondii is an
intracellular parasite which is capable of forming tissue cysts in brain of
chronically infected hosts including humans. Some epidemiological studies
suggested an association between toxoplasmosis and acquisition of epilepsy. In
this study we determined seroprevalence of latent Toxoplasma infection in a
population of Iranian epileptic patients. Participants were classified in three
groups as Iranian epileptic patients (IEP, n = 414), non-epileptic patients who
had other neurologic disorders (NEP, n = 150), and healthy people without any
neurologic disorders (HP, n = 63). The presence of anti-Toxoplasma IgG antibodies
and IgG titer in the sera were determined by ELISA method. Anti-T. gondii IgG
seroprevalence obtained 35.3 %, 34.7 % and 38.1 % in IEP, NEP and HP,
respectively. The seroprevalence rate was not significantly different among the
three groups (P = 0.88). Anti-T. gondii IgG titer was 55.7 +/- 78, 52.4 +/- 74
and 69.7 +/- 92 IU/ml in IEP, NEP and HP, respectively. There was not any
statistically significant difference in the antibody titer between the study
groups (P = 0.32). The rate of T. gondii infection in epileptic patients was not
higher than non-epileptic patients and healthy people in the Iranian population.
PMID- 28507472
TI - Schisandrae Fructus ethanol extract ameliorates inflammatory responses and
articular cartilage damage in monosodium iodoacetate-induced osteoarthritis in
rats.
AB - Schisandrae Fructus, the fruit of Schisandra chinensis (Turcz.) Baill., is widely
used in traditional medicine for the treatment of a number of chronic diseases.
Although, Schisandrae Fructus was recently reported to attenuate the interleukin
(IL)-1beta-induced inflammatory response in chondrocytes in vitro, its protective
and therapeutic potential against osteoarthritis (OA) in an animal model remains
unclear. Therefore, we investigated the effects of the ethanol extract of
Schisandrae Fructus (SF) on inflammatory responses and cartilage degradation in a
monosodium iodoacetate (MIA)-induced OA rat model. Our results demonstrated that
administration with SF had a tendency to attenuate MIA-induced damage of
articular cartilage as determined by a histological grade of OA. SF significantly
suppressed the production of pro-inflammatory cytokines such as interleukin (IL)
1beta, IL-6, and tumor necrosis factor-alpha in MIA-induced OA rats. SF also
effectively inhibited expression of inducible nitric oxide (NO) synthase and
cyclooxygenase-2, thereby inhibiting the release of NO and prostaglandin E2. In
addition, the elevated levels of matrix metalloproteinases-13 and two biomarkers
for diagnosis and progression of OA, such as cartilage oligomeric matrix protein
and C-telopeptide of type II collagen, were markedly ameliorated by SF
administration. These findings indicate that SF could be a potential candidate
for the treatment of OA.
PMID- 28507473
TI - Effects of symbiotic and vitamin E supplementation on blood pressure, nitric
oxide and inflammatory factors in non-alcoholic fatty liver disease.
AB - Non-alcoholic fatty liver disease (NAFLD) has been suggested to be well
correlated with altered blood pressure. This study was conducted to determine the
effects of symbiotic and vitamin E supplementation on blood pressure and
inflammatory indices of patients with NAFLD. This randomized, double-blind,
placebo-controlled trial was performed among 60 NAFLD patients aged 25 to 64
years old. Participants were randomly divided into four groups to receive a 400
IU alpha-tocopherol and 2 * 108 CFU/g symbiotic supplement for 8 weeks. The
anthropometric parameters, systolic blood pressure (SBP) and diastolic blood
pressure (DBP), serum malondialdehyde (MDA), nitric oxide (NO) and tumor necrosis
factor alpha (TNFalpha) were assessed at baseline and after 8 weeks of
intervention. After 8 weeks of intervention, combined symbiotic and alpha
tocopherol, symbiotic and alpha-tocopherol alone administration, compared with
the placebo, resulted in significant decreases in SBP (-17.07+/-2.1, -16.07+/
3.56, -1.73+/-2.25 and -1.55+/-3.01 mmHg, P=0.01), serum MDA (-1.19+/-0.5,
0.12+/-0.65, 0.14 +/- 0.64 and 0.16+/-0.34 nmol/mL, P<0.001), serum TNFalpha (
15.62+/-13.93, -9.24+/-7.12, -11.44 +/- 15.47 and 3.01+/-1.71 pg/ml, P<0.001)
concentrations. A significant decrease in serum AST (-11.36+/-4.52, -7.43+/-8.58,
-5.93+/-6.61 and 2.5+/-5.75 MUmol/L, P <0.001), ALT (-12.79+/-3.65, -3.66+/-6.81,
-6.54+/-7.66 and 4.16+/-3.43 MUmol/L, P <0.001) and ALP (-26.8+/-11.1, -4.56+/
9.22, -14.48+/-12.22 and 5.19+/-2.64 MUmol/L, P <0.001) was seen. Variations in
DBP and serum NO concentration were not significant. Alpha-tocopherol and
symbiotic supplementation among patients with NAFLD resulted in decreased SBP,
serum MDA, TNFalpha levels and enzymes liver; however, they did not affect DBP
and serum NO concentration.
PMID- 28507474
TI - Anacardium microcarpum extract and fractions protect against paraquat-induced
toxicity in Drosophila melanogaster.
AB - Anacardium microcarpum Ducke (Anacardiaceae) is a native species of Brazil used
in folk medicine for the treatment of several illnesses although its antioxidant
activity has been reported in vitro, there is no evidence of this effect in an in
vivo model. Here, we investigated the potential protective effect of
hydroalcoholic extract (AMHE), methanol (AMMF) and acetate (AMAF) fraction of A.
microcarpum against paraquat toxicity on survivorship, locomotor performance,
antioxidant enzymes activity and reactive species using Drosophila melanogaster.
Flies were exposed to the extract or fractions (1 and 10 mg/ml) in the presence
or absence of paraquat (5 mM) in sucrose solution for 72 h. In addition, total
phenolic content of extract and fractions was evaluated as well as ABTS radical
scavenging capacity. Our results demonstrated that AMAF presented higher content
of phenols and ABTS chelating potential. Treatment of flies with the extract or
fractions did not alter the survivorship, locomotor ability, and
acetylcholinesterase (AchE) activity per se. Paraquat caused 85 % mortality of
flies and 30 % increase in reactive species generation, which were significantly
attenuated by AMHE and AMMF. AAMF increased catalase activity (from 66.77 +/-
6.64 to 223.94 +/- 25.92 mU/mg of protein), while AMAF increased GST activity
(from 477.76 +/- 92 to 770.19 +/- 147.92 mU/mg of protein) and catalase activity
(from 66.77 +/- 6.64 to 220.54 +/- 26.63 mU/mg of protein). AMHE and AMMF were
more effective in protecting against paraquat toxicity. Taken together, the data
indicate the potential of this plant in acting as a protective and antioxidant
agent in vivo.
PMID- 28507475
TI - Macrophage migration inhibitory factor -173 G > C polymorphism and risk of
tuberculosis: A meta-analysis.
AB - The aim of the present meta-analysis was to find out the impact of MIF -173 G > C
polymorphism on risk of tuberculosis (TB). We conducted a search of case-control
studies on the associations of -173 G > C variant of MIF with susceptibility to
tuberculosis in PubMed, ISI Web of Science, and Scopus. We extracted the data
from eligible studies and achieved a meta-analysis to examine the relationship
between MIF -173 G > C polymorphism and the risk of TB. Odds ratios (ORs) with
the corresponding 95 % confidence intervals (CIs) were pooled to find out the
impact of MIF -173G > C promoter polymorphism on TB risk. The pooled ORs were
calculated for the codominant, dominant, recessive, and allelic model comparison.
The findings revealed that MIF -173 G > C variant increased the risk of TB in
codominant (OR = 1.54, 95 %CI = 1.26-1.88, p < 0.0001; CG vs GG), and dominant
(OR = 1.62, 95 %CI = 1.33-1.96, p < 0.00001; GC+CC vs GG) inheritance models
tested. The results suggested that the MIF -173 C allele significantly increased
the risk of PTB (OR = 1.49, 95 %CI = 1.28-1.74, p < 0.00001). The findings of
this meta-analysis propose that MIF -173 G > C variant is associated with the
risk of TB. More case-control studies with well-designed in different ethnic
groups and larger sample size are needed to confirm the findings.
PMID- 28507476
TI - Effect of clopidogrel on the hydroxylation and sulfoxidation of omeprazole: A
single dose study in healthy human volunteers.
AB - Based upon the known potential interaction between omeprazole (OMP) and
clopidogrel (CLOP), the current study was designed to evaluate the effect of CLOP
on disposition of OMP and its two major metabolites, 5-hydroxyomeprazole (5-OH
OMP) and omeprazole sulfone (OMP-S) in healthy clinical subjects. A randomized,
open label, 2-period, crossover study was designed. Twelve volunteers were
selected, of whom eight were extensive metabolizers (EM) of CYP2C19 and 4 were
poor metabolizers (PM). They received single dose of OMP either alone or in
combination with CLOP (single dose) and samples were collected periodically to
calculate various pharmacokinetic parameters. Changes in most of the
pharmacokinetic parameters of OMP, 5-OH-OMP and OMP-S were insignificant (P ?
0.05) both in EM and PM except for the maximum concentration (Cmax) of 5-OH-OMP
and OMP-S in EM. The OMP Cmax and AUC0-infinity was increased both in EM and PM
after concomitant administration of OMP with CLOP. The 5-OH-OMP Cmax was
decreased in both EM and PM, demonstrating that CLOP inhibits hydroxylation of
OMP. The OMP-S Cmax and AUC0-infinity were increased both in EM and PM showing
that CLOP may induce sulfoxidation of OMP. It was concluded that CLOP may inhibit
hydroxylation of OMP to a greater extent in EM than in PM, leading to higher OMP
Cmax and AUC0-infinity. Furthermore, the sulfoxidation of OMP may also be induced
by CLOP. So, it is suggested that both these drugs should be carefully prescribed
together to avoid any harm to the patients. (Application number13/EC/Pharm. Ref
number 12/Pharm).
PMID- 28507477
TI - Enzymatic hydrolysate from velvet antler suppresses adipogenesis in 3T3-L1 cells
and attenuates obesity in high-fat diet-fed mice.
AB - The purpose of the current study was to investigate the potential anti-obesity
activity of an enzymatic hydrolysate of velvet antler in inhibiting adipogenesis
in 3T3-L1 cells and in high-fat diet (HFD)-fed obese mice. The enzymatic
hydrolysate was prepared using the commercial food grade protease, Protamex. The
velvet antler Protamex hydrolysate (VAPH) indicated profound inhibitory effects
on adipogenesis dose-dependently by decreasing the accumulation of triglycerides
and down-regulating expression levels of adipogenesis-related proteins
C/EBPalpha, SREBP-1, and PPARgamma. In a mouse model of HFD-induced obesity, oral
administration of VAPH (100 and 300 mg/kg for 13 weeks) significantly reduced the
body weight gain that had resulted from the HFD. VAPH treatment also lowered the
serum glucose and triglyceride levels, while increasing the HDL-C level.
Furthermore, the treatment greatly reduced hepatic lipid droplet accumulation as
well as the size of adipocytes. Current findings demonstrate that VAPH has
profound anti-obesity effects and could be an effective candidate for preventing
obesity and obesity-related chronic diseases.
PMID- 28507479
TI - Knockdown of lncRNA-PANDAR suppresses the proliferation, cell cycle and promotes
apoptosis in thyroid cancer cells.
AB - Long non-coding RNAs (lncRNAs) have been found to show important regulatory roles
in various human cancers. Lnc-RNA PANDAR is a novel identified lncRNA that was
previously reported to show abnormal expression pattern in various cancers.
However, little is known of its expression and biological function in thyroid
cancer. Here, we used the quantitative real-time PCR (qRT-PCR) to determine the
expression of PANDAR in 64 thyroid cancer tissues. We found that expression of
PANDAR was up-regulated in thyroid cancer tissues compared with adjacent non
tumor tissues. Functional assays in vitro demonstrated that knockdown of PANDAR
could inhibit proliferation, cell cycle progression, induces the apoptosis,
inhibit invasion of thyroid cancer cells. Thus, our study provides evidence that
PANDAR may function as a potential target for treatment for patients with thyroid
cancer.
PMID- 28507478
TI - Melatonin regulates the aging mouse hippocampal homeostasis via the sirtuin1
FOXO1 pathway.
AB - Sirtuin1 (SIRT1) and forkhead box transcription factor O subfamily 1 (FOXO1) play
vital roles in the maintenance of hippocampal neuronal homeostasis during aging.
Our previous study showed that melatonin, a hormone mainly secreted by the pineal
gland, restored the impaired memory of aged mice. Age-related neuronal energy
deficits contribute to the pathogenesis of several neurodegenerative disorders.
An attempt has been made to determine whether the effect of melatonin is mediated
through the SIRT1-FOXO1 pathways. The present results showed that aged mice (22
months old) exhibited significantly downregulated SIRT1, FOXO1, and melatonin
receptors MT1 and MT2 protein expression but upregulated tumor suppressor protein
53 (p53), acetyl-p53 protein (Ac-p53), mouse double minute 2 homolog (MDM2),
Dickkopf-1 (DKK1) protein expression in mouse hippocampus compared with the young
group. Melatonin treatment (10 mg/kg, daily in drinking water for 6 months) in
aged mice significantly attenuated the age-induced downregulation of SIRT1,
FOXO1, MT1 and MT2 protein expression and attenuated the age-induced increase in
p53, ac-p53, MDM2, and DKK1 protein and mRNA expression. Melatonin decreased p53
and MDM2 expression, which led to a decrease in FOXO1 degradation. These present
results suggest that melatonin may help the hippocampal neuronal homeostasis by
increasing SIRT1, FOXO1 and melatonin receptors expression while decreasing DKK1
expression in the aging hippocampus. DKK1 can be induced by the accumulation of
amyloid beta (Abeta) which is the major hallmark of Alzheimer's disease.
PMID- 28507480
TI - Electro-acupuncture promotes the proliferation of neural stem cells and the
survival of neurons by downregulating miR-449a in rat with spinal cord injury.
AB - The aim of this study is to investigate the mechanism of electro-acupuncture (EA)
on the recovery of injured spinal cord. Rats were randomly divided into normal
control, sham-operated, SCI, SCI+EA group and T10 segment spinal cord injury
(SCI) rat model was established by the modified Allen's method. After 7 days, the
mRNA and protein expression of Nestin, neuron specific nuclear protein (NeuN) and
calcitonin gene related peptide (CGRP) were detected by real time RT-PCR, Western
blot and immunohistochemistry respectively. The protein expression of cleaved
caspase 3, Bax, Bcl-2, TNF-alpha and IL-1beta were also detected by Western blot.
MicroRNA 449a (miR-449a) expression was also compared. Further, 12 SCI rats were
randomly divided into EA and miR subgroups (EA + miR-449a agomir injection). The
expression of Nestin, NeuN, CGRP, cleaved caspase 3, Bax, Bcl-2, TNF-alpha, IL
1beta and miR-449a was compared. The direct interaction of miR-449a and CGRP mRNA
was assessed by dual luciferase reporter assay. At day 7, compared with sham
operated group, miR-449a expression in SCI group was significantly increased (P <
0.05), and NeuN and CGRP mRNA and protein expression was markedly decreased (P <
0.05), but protein levels of Nestin, cleaved caspase 3, TNF-alpha, IL-1beta and
the ratio of Bax/Bcl-2 in SCI group were significantly increased (P < 0.05). The
EA treatment significantly reduced miR-449a level and cleaved caspase 3, TNF
alpha, IL-1beta level and the ratio of Bax/Bcl-2 (P < 0.01), but substantially
increased Nestin, NeuN and CGRP expression (P < 0.05 or 0.01). High level of miR
449a in miR subgroup was accompanied by decreased expression of Nestin, NeuN and
CGRP and increased expression of cleaved caspase 3, TNF-alpha, IL-1beta and
elevation of the ratio of Bax/Bcl-2 (P < 0.05), suggesting miR-449a inhibits the
effects of EA on NSCs and neurons. Luciferase reporter assay showed that miR-449a
bound to the 3' UTR of CGRP, and thereby regulated CGRP expression. In
conclusion, EA promotes proliferation of neural stem cells and the survival of
neurons by downregulation of miR-449a expression.
PMID- 28507481
TI - Isolation and characterization of phthalates from Brevibacterium mcbrellneri that
cause cytotoxicity and cell cycle arrest.
AB - Bacteria belonging to the family Brevibacterieae are ubiquitous Gram positive
organisms that are responsible for the feet odour and cheese aroma.
Brevibacterium mcbrellneri is a relatively new member belonging to
Brevibacterieae. In the current manuscript we discuss isolation of biologically
active metabolites from Brevibacterium mcbrellneri. Two aromatic esters were
isolated from Brevibacterium mcbrellneri by "Bioassay guided fractionation
strategy" and identified as di-(2-ethylhexyl) phthalate and dibutyl phthalate by
chemical characterization using biophysical techniques. The phthalate compounds
show broad spectrum antibacterial activity and mosquito larvicidal activity.
Mosquito larvicidal activity has been attributed to inhibition of
acetylcholinesterase enzyme activity. These compounds were found to be cytotoxic
in multiple cell lines causing cell cycle arrest in G1 phase.
PMID- 28507482
TI - Gentamicin nephrotoxicity in animals: Current knowledge and future perspectives.
AB - Due to high relative blood flow the kidney is prone to drug-induced damage.
Aminoglycoside type antibiotic gentamicin is one of the leading cause of drug
induced nephrotoxicity. In recent years gentamicin nephrotoxicity is
significantly reduced by shifting to once daily dosage as well as by eliminating
known risk factors. Application of gentamicin is still related to serious side
effects which are reported more often compared to other antibiotics. Because
gentamicin is still heavily used and is highly efficient in treating infections,
it is important to find mechanisms to reduce its nephrotoxicity. This aim can
only be achieved through better understanding of kidney metabolism of gentamicin.
This problem has been extensively researched in the last 20 years. The
experimental results have provided evidence for almost complete understanding of
mechanisms responsible for gentamicin nephrotoxicity. We now have well described
morphological, biochemical and functional changes in kidney due to gentamicin
application. During the years, this model has become so popular that now it is
used as an experimental model for nephrotoxicity per se. This situation can
mislead an ordinary reader of scientific literature that we know everything about
it and there is nothing new to discover here. But quite opposite is true. The
precise and complete mechanism of gentamicin nephrotoxicity is still point of
speculation and an unfinished story. With emerge of new and versatile technics in
biomedicine we have an opportunity to reexamine old beliefs and discover new
facts. This review focuses on current knowledge in this area and gives some
future perspectives.
PMID- 28507484
TI - Imaging and Analysis of Encapsulated Objects through Self-Assembled Electron and
Optically Transparent Graphene Oxide Membranes.
AB - We demonstrate a technique for facile encapsulation and adhesion of micro- and
nano objects on arbitrary substrates, stencils, and micro structured surfaces by
ultrathin graphene oxide membranes via a simple drop casting of graphene oxide
solution. A self-assembled encapsulating membrane forms during the drying process
at the liquid-air and liquid-solid interfaces and consists of a water-permeable
quasi-2D network of overlapping graphene oxide flakes. Upon drying and
interlocking between the flakes, the encapsulating coating around the object
becomes mechanically robust, chemically protective, and yet highly transparent to
electrons and photons in a wide energy range, enabling microscopic and
spectroscopic access to encapsulated objects. The characteristic encapsulation
scenarios were demonstrated on a set of representative inorganic and organic
micro and nano-objects and microstructured surfaces. Different coating regimes
can be achieved by controlling the pH of the supporting solution, and the
hydrophobicity and morphology of interfaces. Several specific phenomena such as
compression of encased objects by contracting membranes as well as hierarchical
encapsulations were observed. Finally, electron as well as optical microscopy and
analysis of encapsulated objects along with the membrane effect on the image
contrast formation, and signal attenuation are discussed.
PMID- 28507483
TI - Effects of hesperidin on formaldehyde-induced toxicity in pregnant rats.
AB - This experimental study aimed to investigate the protective effect of a
bioflavonoid, hesperidin (HP), on formaldehyde (FA)-related pathophysiological
and behavioral outcomes in pregnant rats and developmental aspects in their
offspring. Female Wistar rats were subjected to perigestational exposure to FA (2
mg/kg/day per os) with a concomitant treatment with HP (50 mg/kg/day per os).
Pregnant rats were weighed throughout gestation and tested in two behavioral
paradigms (elevated plus-maze and open field) at gestational days (GD) 1, 10 and
19 to evaluate the anxiety-like behavior and locomotive alterations. Another
subset of rats was decapitated at GD19 to determine the hematological profile
along with cortisol, 17beta-estradiol, and progesterone plasma levels.
Reproductive and fetal measures and observations were also performed to check for
developmental deformities. Significant body weight loss, hemato-immune decline,
hormonal changes, anxiety and lethargy signs, locomotor disabilities,
reproductive failure and fetal weight decrease were observed in FA-exposed rats.
Treatment with HP alleviated the reproductive and fetal weight defects. Its
behavioral benefits were only seen at GD1 and 10. This flavanone ameliorated some
hematological parameters, decreased cortisol levels and increased 17beta
estradiol rates. A potential preventive impact of HP was found against FA
toxicity in pregnant rats.
PMID- 28507486
TI - Melanin and lipofuscin as hallmarks of skin aging.
AB - Discoloration are symptoms of skin aging. They are connected with presence of
melanin and lipofuscin, whose excess and abnormal distribution in the skin cause
dark spots to appear. Melanin is formed under the influence of tyrosinase during
melanogenesis. Its content changes with age, which may be a result of menopause.
Lipofuscin is another example of the age pigment. It is composed of proteins,
lipids and carbohydrates. It is described as an age pigment because its content
increases with age. The formation and accumulation of lipofuscin is inevitable
and leads to cell and homeostasis dysfunction because it reduces the proteasome
activity.
PMID- 28507485
TI - The influence of dietary immunomodulatory factors on development of food allergy
in children.
AB - In the last few years many studies have been conducted on the role of dietary and
environmental factors in the prevention of allergic diseases among children. Many
studies have shown that the diet of pregnant women and children in their early
postnatal life, rich in antioxidants, vitamin D, and fatty acids is beneficial as
it reduces the risk of allergy in their future life. Moreover, there are many
reports about the main role of gut microbiota and probiotics in the allergy
prevention, what can indicate new ways of procedures in allergic diseases.
PMID- 28507488
TI - Microbiological analysis of acute infections of the nail fold on the basis of
bait thread test.
AB - INTRODUCTION: An acute infection of the nail fold, called paronychia, is a common
clinical problem. The basis for the implementation of the treatment is the result
of microbiological examination. Due to the rapid and painful course of infection,
usually an empirical antimicrobial treatment prior to obtaining microbiological
test results is introduced. AIM: The microbial analysis of acute infections of
the nail fold. MATERIAL AND METHODS: The study included 32 tests conducted on 31
patients of the Department of Dermatology. Microbiological analysis was performed
with the use of the so-called bait thread test. RESULTS: In 73% of analyzed cases
microbiological examination revealed mixed microbiological flora. Most cultured
microorganisms were: Enterococcus faecalis (14%), Staphylococcus aureus (12%),
Candida albicans (9%), Enterobacter cloacae (8%), and Klebsiella pneumoniae (7%).
Most cultured bacteria belonged to the families or genera of Enterobacteriaceae
(36%), other cultured bacteria were staphylococci (26%), enterococci (16%),
Candida species (14%), and Gram-negative non-fermenting bacilli (8%).
CONCLUSIONS: The acute infection of the nail fold in the vast majority of cases
is caused by mixed bacterial flora. A profile of isolated microorganisms suggests
that the cause of the infection can be associated with neglect of hygiene.
Fluoroquinolone and fusidic acid are recommended as the empirical therapy.
Microbiological examination is the basis for the appropriate final treatment.
PMID- 28507487
TI - Demographic characteristics, aetiology, and assessment of treatment options in
leukocytoclastic vasculitis.
AB - INTRODUCTION: Vasculitides are a heterogeneous group of diseases characterized by
inflammation of the blood vessel walls. Etiological factors include infections,
drugs, connective tissue diseases, and malignancies. AIM: To examine the
demographic characteristics, etiological factors, and treatment options in 75
patients with leukocytoclastic vasculitis. MATERIAL AND METHODS: The study
included 75 patients diagnosed with leukocytoclastic vasculitis at our clinic.
The patients' medical records were reviewed to determine their age, sex, presence
of systemic symptoms, possible etiological factors, laboratory results, types of
cutaneous lesions, locations of the lesions, treatment options, and disease
course. RESULTS: There were 43 women and 32 men. Cutaneous lesions affected only
the lower limbs in 60 of the 75 patients (80%) and usually presented as palpable
purpura (64%, n = 48). Arthralgia (26.7%, n = 20) was the most frequent
extracutaneous symptom. Of the patients with secondary vasculitis, the most
common causes were infections and drugs. The mean age of the patients with Henoch
Schonlein purpura was 26.8 years. There was no significant association between
age and renal, gastrointestinal, or joint involvement. CONCLUSIONS: The most
common form of vasculitis in our study was cutaneous leukocytoclastic vasculitis.
In most of the patients it appeared to be idiopathic. Among drugs, antibiotics
were the most common etiological factor. In 4 patients, the cutaneous
leukocytoclastic vasculitis behaved like the paraneoplastic syndrome.
PMID- 28507489
TI - Evaluation of the serum zinc level in patients with vitiligo.
AB - INTRODUCTION: Vitiligo is an acquired, idiopathic disorder characterized by
circumscribed depigmented macules and patches, which affects approximately 0.1-2%
of the general population worldwide. Zinc is an essential trace element that is
necessary for growth and development at all stages of life. Some studies have
reported an association between serum zinc levels and vitiligo. AIM: To measure
the serum zinc level in patients with vitiligo compared to healthy subjects.
MATERIAL AND METHODS: One hundred patients with vitiligo and 100 healthy controls
were referred to our clinic. The two groups were matched for age and sex. Atomic
absorption spectrophotometry was used to measure serum zinc levels. The
statistical analysis was performed using SPSS software. RESULTS: The mean serum
level of zinc in vitiligo patients and controls was 80.11 +/-17.10 MUg/dl and
96.10 +/-16.16 MUg/dl, respectively. The serum zinc level in patients with
vitiligo was significantly lower than in healthy controls (p = 0.0001).
CONCLUSIONS: The results of our study revealed a significant association between
vitiligo and serum zinc levels. A relative decrease in the serum zinc level in
vitiligo patients can highlight the role of zinc in the pathogenesis of vitiligo,
and large-scale studies need to be conducted to confirm these findings and assess
the effect of oral zinc supplements in patients with low zinc levels.
PMID- 28507490
TI - Cognitive impairment in patients with severe psoriasis.
AB - INTRODUCTION: Psoriasis is a chronic inflammatory skin disease, in which an
important role is played by psychological factors. AIM: To evaluate the frontal
cognitive functions in patients with psoriasis. MATERIAL AND METHODS: The study
included 188 subjects (97 patients with psoriasis and 91 healthy controls). To
assess the dorsolateral prefrontal cortex functions, the Trail Making Test and
the Stroop test were applied. Severity of psoriasis was assessed by means of the
PASI index. RESULTS: Compared to healthy subjects, psoriatics scored lower in
neuropsychological tests assessing memory and executive functions. CONCLUSIONS:
Cognitive dysfunction disclosed by neuropsychological assessment of frontal
functions was evident in patients with psoriasis.
PMID- 28507491
TI - Association between mean platelet volume and disease severity in patients with
psoriasis and psoriatic arthritis.
AB - INTRODUCTION: Mean platelet volume (MPV) is an important marker that shows the
activation and function of the platelets, which is effective in the inflammatory
diseases. AIM: To show the relationship between MPV and the development of
psoriatic arthritis (PA) in patients with psoriasis vulgaris (PV) and the
correlation between MPV and psoriasis severity score (PASI). MATERIAL AND
METHODS: Our study included 116 patients with psoriatic arthritis (68 female, 48
male) and 41 patients in the psoriasis group (19 female, 22 male) and 90 subjects
in the control group (55 female, 35 male). The demographic data of the patients,
duration of disease, PASI, the nature of the disease were evaluated
retrospectively. RESULTS: Mean platelet volume levels of both the PV group (8.79
+/-0.86 fl) and the PA group (9.18 +/-1.26 fl) were significantly higher compared
to the control group (8.42 +/-0.74 fl). There was a weak statistically positive
correlation between the PASI and the MPV according to the correlation analysis (r
= 0.165; p = 0.046). CONCLUSIONS: Our results show that MPV may be helpful as an
indicator of the clinical course of PV and PA. In this regard, that study should
be supported by prospective studies to find strong correlations.
PMID- 28507492
TI - Long-term treatment of chronic plaque psoriasis with biological drugs can control
platelet activation: targeting the bridge between inflammation and
atherothrombosis.
AB - INTRODUCTION: Platelet activation is elevated in moderate to severe psoriasis,
and the reduction in platelet activation during short-term treatment has already
been demonstrated. Soluble P-selectin is a well-established marker of platelet
activation. AIM: To show whether the long-term treatment of psoriasis with
biological drugs can reduce elevated platelet activation. MATERIAL AND METHODS:
An observational study of 27 patients with chronic plaque psoriasis, treated with
infliximab, adalimumab, etanercept, or ustekinumab for up to 12 months was
conducted. Psoriasis area and severity index (PASI), serum P-selectin and
interleukin (IL)-6 were monitored throughout the treatment. RESULTS: There was no
significant correlation between PASI and platelet activation in our patients.
After 3 months of treatment, a significant reduction in PASI and IL-6 was found,
while P-selectin was not significantly reduced. When a cohort of patients who had
shown elevated P-selectin prior to the treatment was evaluated, a significant
reduction in P-selectin was observed in all 8 patients following 3 months; a
reduction that was sustained after 6 and 12 months of therapy. CONCLUSIONS: We
conclude that PASI is not a good predictor of platelet activity in patients with
PASI near to 10. Biological drugs reduce platelet activation in patients who have
increased platelet activation prior to treatment, and this effect is stable
during chronic therapy.
PMID- 28507493
TI - Comparison of the incidence of skin cancers in patients on dialysis and after
kidney transplantation.
AB - INTRODUCTION: Kidney transplant (KTx) patients on immunosuppressive therapy are
predisposed to the development of infections and cancers. AIM: To compare the
incidence and type of malignant skin lesions in kidney transplant patients and
the dialyzed population based on the initiated dermatologic screening. MATERIAL
AND METHODS: The study included 598 patients: 486 kidney transplant recipients
and 112 patients on maintenance dialysis. All the patients underwent
dermatological examination. Only histologically confirmed cancers were included
in this study. Age, gender and immunosuppressive therapy administration were also
considered. Patients were followed up by a dermatologist for a period of 5 years.
RESULTS: Fifty-eight skin cancers; 39 basal cell carcinomas (BCC), 13 squamous
cell carcinomas (SCC), 1 Bowen disease, 2 Kaposi sarcoma, 1 malignant melanoma, 1
Merkel cell carcinoma, and 1 fibrosarcoma protuberans were diagnosed in 30 (6.2%)
kidney transplant patients, and 8 lesions (7 BCC and 1 SCC) were found in 4
(3.6%) patients on dialysis. CONCLUSIONS: The initiated dermatologic screening
program indicates that the risk of skin cancer incidence in post kidney
transplant patients receiving immunosuppressive therapy was significantly higher
than in patients on dialysis.
PMID- 28507494
TI - Sleep patterns of young children with newly diagnosed atopic dermatitis.
AB - INTRODUCTION: Even though atopic dermatitis (AD) most often begins in the first
year of life, it is not well known whether sleep disturbances occur following the
onset of the disease or whether they develop later. AIM: To determine the sleep
patterns of young children already diagnosed with AD in comparison to a control
group by using a validated questionnaire, the Brief Infant Sleep Questionnaire
(BISQ). MATERIAL AND METHODS: Forty-six children with a new diagnosis of AD and
60 healthy children, aged 3-36 months, participated in the study. Their sleep
behaviors were assessed using the BISQ along with a structured sociodemographic
data form. RESULTS: It was found that when compared with healthy children,
children with AD did not have decreased daily total sleep duration (p = 0.1);
however, it was found that they woke up more frequently at night (52.2% vs. 40%,
p = 0.4) and they stayed awake significantly longer than 60 min when they woke up
(41.3% vs. 11.7%, p < 0.05). In addition, mothers of children with AD reported
that their children had three times as many sleep problems compared to the
reports of mothers of healthy children. CONCLUSIONS: The findings of this study
showed that sleep disturbance was more common in young children with already
diagnosed AD, and the BISQ provided a practical way to assess the sleep patterns.
The use of a screening tool to enable early identification and treatment of
childhood sleep problems among patients with AD should be encouraged.
PMID- 28507495
TI - The pharmacotherapy preferred by doctors in treatment of patients diagnosed with
asthma or chronic obstructive pulmonary disease or allergic rhinitis and
concomitant diseases: an epidemiological analysis.
AB - INTRODUCTION: The clinical course of asthma and chronic obstructive pulmonary
disease (COPD) is influenced by the co-occurrence of other chronic diseases and
their pharmacotherapy. There are no data associated with the doctors'
pharmacotherapy preferences in treatment of patients with asthma, COPD or
allergic rhinitis and concomitant diseases. AIM: The assessment of doctors'
preferences in pharmacotherapy of asthma, COPD or allergic rhinitis in relation
to concomitant diseases. MATERIAL AND METHODS: General practitioners,
pulmonologists, allergists, laryngologists and paediatricians (n = 319)
participated in a questionnaire survey concerning their preferences in
pharmacotherapy of asthma, COPD and allergic rhinitis in relation to concomitant
diseases enrolling 11,310 patients with asthma, COPD and allergic rhinitis.
RESULTS: The concomitant diseases were reported in 58.5% of patients with asthma,
80.8% of patients with COPD and 46.4% of patients with allergic rhinitis.
Patients with asthma were most frequently treated with inhaled
glucocorticosteroids. However, in the subgroups with concomitant diseases, an
increased usage of inhaled long-acting beta2-mimetics was noted. Regardless of
comorbidities, patients with COPD were most frequently treated with inhaled long
acting beta2-mimetics whereas patients with allergic rhinitis - with nasal
glucocorticosteroids and third-generation antihistamines. CONCLUSIONS: The co
occurrence of chronic diseases was most frequent among patients diagnosed with
COPD. The treatment of asthma, COPD and allergic rhinitis is consistent with
international recommendations and the occurrence of concomitant diseases did not
significantly influence therapeutic preferences and decisions.
PMID- 28507498
TI - Pruritus ani and perianal eczema as a manifestation of systemic contact
dermatitis.
PMID- 28507496
TI - Safety and efficacy of venom immunotherapy: a real life study.
AB - INTRODUCTION: Venom immunotherapy (VIT) is recommended as the first-line
treatment for patients allergic to Hymenoptera venom. AIM: To analyze the safety
and efficacy of VIT in a real life setting. MATERIAL AND METHODS: One hundred and
eighty patients undergoing VIT were studied to evaluate the safety, efficacy,
incidence and nature of symptoms after field stings and adverse reactions to VIT.
RESULTS: Significantly more patients were allergic to wasp than bee venom (146
vs. 34, p < 0.0001). Early and late side effects were more common during the
maintenance (48 patients, 26.7%) than during the induction of VIT (32 patients,
17.8%), were more frequent in patients allergic to bees, and were not associated
with angiotensin convertase inhibitors (ACEi) or beta-adrenergic antagonists use.
Systemic reactions were observed in 4 individuals on wasp VIT (2.7%) and in 6
patients allergic to bees (17.65%). The VIT was efficacious as most patients
reported no reactions (50%) or reported only mild local reactions (43.75%) to
field stings. The decrease in sIgE at completion of VIT correlated with the dose
of vaccine received (r = 0.53, p = 0.004). Beekeeping (RR = 29.54, p < 0.0001)
and female sex (RR = 1.27, p = 0.033) were associated with a higher risk of venom
allergy. CONCLUSIONS: Venom immunotherapy is highly efficacious and safe as most
of the adverse events during the induction and maintenance phase are mild and
local. Side effects of VIT are more common in subjects on bee VIT. Beekeeping and
female sex are associated with a higher risk of allergy to Hymenoptera venom.
PMID- 28507497
TI - Sense of coherence as a protective factor in chronic urticaria.
AB - INTRODUCTION: Chronic urticaria (CU) seems to be perceived as a
psychodermatological disorder. Different psychological factors play an important
role in CU triggering and course. One of them is a sense of coherence (SOC),
which is believed to be a protective factor against anxiety and depression. AIM:
To investigate quality of life (QoL) in CU patients and to compare selected
psychological parameters (anxiety, depression and sense of coherence) between CU
individuals and the control group. MATERIAL AND METHODS: The study comprised 46
female patients with chronic urticaria and 33 healthy females as a control group.
The following methods were employed: Urticaria Activity Score (UAS), Hospital
Anxiety and Depression Scale (HADS), Sense of Coherence Questionnaire (SOC-29)
and Dermatology Life Quality Index (DLQI). RESULTS: The CU patients presented a
significantly higher anxiety level in comparison to the control group (z = 4.488;
p < 0.001). There were no statistically significant differences regarding
depression intensity and SOC. In both groups anxiety and depression negatively
correlated with global SOC and all its components. Disease severity positively
correlated with QoL (rho = 0.46, p < 0.01) and negatively with global SOC (rho =
0.33, p < 0.05). CONCLUSIONS: Bearing in mind higher prevalence of anxiety and
depressive symptoms in our CU group, it would be useful to perform screening of
these aspects in all CU patients and subsequently develop respective
psychological interventions, based on enhancement of personal resources.
PMID- 28507500
TI - The coexistence of Darier's disease and Hailey-Hailey disease symptoms.
PMID- 28507499
TI - Linear cutaneous lupus erythematosus/discoid lupus erythematosus in an adult.
PMID- 28507501
TI - Supermedicus Award for Professor Cezary Kowalewski.
PMID- 28507502
TI - Node Identification Using Inter-Regional Correlation Analysis for Mapping
Detailed Connections in Resting State Networks.
AB - Brain function is often characterized by the connections and interactions between
highly interconnected brain regions. Pathological disruptions in these networks
often result in brain dysfunction, which manifests as brain disease. Typical
analysis investigates disruptions in network connectivity based correlations
between large brain regions. To obtain a more detailed description of disruptions
in network connectivity, we propose a new method where functional nodes are
identified in each region based on their maximum connectivity to another brain
region in a given network. Since this method provides a unique approach to
identifying functionally relevant nodes in a given network, we can provide a more
detailed map of brain connectivity and determine new measures of network
connectivity. We applied this method to resting state fMRI of Alzheimer's disease
patients to validate our method and found decreased connectivity within the
default mode network. In addition, new measure of network connectivity revealed a
more detailed description of how the network connections deteriorate with disease
progression. This suggests that analysis using key relative network hub regions
based on regional correlation can be used to detect detailed changes in resting
state network connectivity.
PMID- 28507503
TI - Improving Challenge/Skill Ratio in a Multimodal Interface by Simultaneously
Adapting Game Difficulty and Haptic Assistance through Psychophysiological and
Performance Feedback.
AB - In order to harmonize robotic devices with human beings, the robots should be
able to perceive important psychosomatic impact triggered by emotional states
such as frustration or boredom. This paper presents a new type of biocooperative
control architecture, which acts toward improving the challenge/skill relation
perceived by the user when interacting with a robotic multimodal interface in a
cooperative scenario. In the first part of the paper, open-loop experiments
revealed which physiological signals were optimal for inclusion in the feedback
loop. These were heart rate, skin conductance level, and skin conductance
response frequency. In the second part of the paper, the proposed controller,
consisting of a biocooperative architecture with two degrees of freedom,
simultaneously modulating game difficulty and haptic assistance through
performance and psychophysiological feedback, is presented. With this setup, the
perceived challenge can be modulated by means of the game difficulty and the
perceived skill by means of the haptic assistance. A new metric (FlowIndex) is
proposed to numerically quantify and visualize the challenge/skill relation. The
results are contrasted with comparable previously published work and show that
the new method afforded a higher FlowIndex (i.e., a superior challenge/skill
relation) and an improved balance between augmented performance and user
satisfaction (higher level of valence, i.e., a more enjoyable and satisfactory
experience).
PMID- 28507504
TI - Effects of alpha2A Adrenoceptors on Norepinephrine Secretion from the Locus
Coeruleus during Chronic Stress-Induced Depression.
AB - Chronic stressors can often lead to the development of psychological disorders,
such as depression and anxiety. The locus coeruleus (LC) is a stress sensitive
brain region located in the pons, with noradrenergic neurons that project to the
hypothalamus, especially the paraventricular nucleus (PVN) of the hypothalamus.
The purpose of this paper is to better understand how alpha 2A-adrenoceptors
(alpha2A-ARs) and LC-hypothalamus noradrenergic system participate in the
pathophysiological mechanism of depression. In vivo norepinephrine (NE) release
in the PVN triggered by electrical stimulation in the LC was detected with carbon
fiber electrodes in depression model of rats induced by chronic unpredictable
mild stress (CUMS). Also, the extracellular level of NE in the PVN was measured
by microdialysis in vivo without any stimulation in the LC. The alpha 2
adrenoceptor (alpha2-AR) antagonist yohimbine and alpha2A-ARs antagonist BRL
44408 maleate were systemically administered to rats to determine the effects of
alpha2A-ARs on NE release in the PVN. The peak value of elicited NE release
signals in the PVN induced by electrical stimulation in the LC in the CUMS rats
were lower than that in the control rats. The extracellular levels of NE in the
PVN of the CUMS rats were significantly less than that of the control rats.
Intraperitoneal injection of yohimbine or BRL-44408 maleate significantly
potentiated NE release in the PVN of the CUMS rats. The CUMS significantly
increased protein expression levels of alpha2A-AR in the hypothalamus, and BRL
44408 maleate significantly reversed the increase of alpha2A-AR protein
expression levels in the CUMS rats. Our results suggest that the CUMS could
significantly facilitate the effect of alpha2-adrenoceptor-mediated presynaptic
inhibition and decrease the release of NE in the PVN from LC. Blockade of the
inhibitory action of excessive alpha2A-adrenergic receptors in the CUMS rats
could increase the level of NE in the PVN, which is effective in the treatment of
depressive disorders.
PMID- 28507506
TI - Differential Regulation of PI(4,5)P2 Sensitivity of Kv7.2 and Kv7.3 Channels by
Calmodulin.
AB - HIGHLIGHTS - Calmodulin-dependent Kv7.2 current density without the need of
binding calcium.- Kv7.2 current density increase is accompanied with resistance
to PI(4,5)P2 depletion.- Kv7.3 current density is insensitive to calmodulin
elevation.- Kv7.3 is more sensitive to PI(4,5)P2 depletion in the presence of
calmodulin.- Apo-calmodulin influences PI(4,5)P2 dependence in a subunit specific
manner. The identification and understanding of critical factors regulating M
current functional density, whose main components are Kv7.2 and Kv7.3 subunits,
has profound pathophysiological impact given the important role of the M-current
in neuronal excitability control. We report the increase in current density of
Kv7.2 channels by calmodulin (CaM) and by a mutant CaM unable to bind Ca2+
(CaM1234) revealing that this potentiation is calcium independent. Furthermore,
after co-expressing a CaM binding protein (CaM sponge) to reduce CaM cellular
availability, Kv7.2 current density was reduced. Current inhibition after
transient depletion of the essential Kv7 co-factor phosphatidylinositol-4,5
bisphosphate (PI(4,5)P2) by activating Danio rerio voltage sensitive phosphatase
(DrVSP) was blunted by co-expressing CaM1234 or the CaM sponge. In addition, CaM
dependent potentiation was occluded by tonic elevation of PI(4,5)P2 levels by
PI(4)P5-kinase (PIP5K) expression. In contrast to the effect on homomeric Kv7.2
channels, CaM1234 failed to potentiate heteromeric Kv7.2/3 or homomeric Kv7.3
channels. Sensitivity to PI(4,5)P2 depletion of Kv7.2/3 channels was increased
after expression of CaM1234 or the CaM sponge, while that of homomeric Kv7.3 was
unaltered. Altogether, the data reveal that apo-CaM influences PI(4,5)P2
dependence of Kv7.2, Kv7.2/3, and of Kv7.3 channels in a subunit specific manner.
PMID- 28507505
TI - Protein-Protein Interaction Among the FoxP Family Members and their Regulation of
Two Target Genes, VLDLR and CNTNAP2 in the Zebra Finch Song System.
AB - The Forkhead transcription factor FOXP2 is implicated in speech perception and
production. The avian homolog, FoxP2 contributes to song learning and production
in birds. In human cell lines, transcriptional activity of FOXP2 requires homo
dimerization or dimerization with paralogs FOXP1 or FOXP4. Whether FoxP
dimerization occurs in the brain is unknown. We recently showed that FoxP1, FoxP2
and FoxP4 (FoxP1/2/4) proteins are co-expressed in neurons of Area X, a song
control region in zebra finches. We now report on dimer- and oligomerization of
zebra finch FoxPs and how this affects transcription. In cell lines and in the
brain we identify homo- and hetero-dimers, and an oligomer composed of FoxP1/2/4.
We further show that FoxP1/2 but not FoxP4 bind to the regulatory region of the
target gene Contactin-associated protein-like 2 (CNTNAP2). In addition, we
demonstrate that FoxP1/4 bind to the regulatory region of very low density
lipoprotein receptor (VLDLR), as has been shown for FoxP2 previously.
Interestingly, FoxP1/2/4 individually or in combinations regulate the promoters
for SV40, zebra finch VLDLR and CNTNAP2 differentially. These data exemplify the
potential for complex transcriptional regulation of FoxP1/2/4, highlighting the
need for future functional studies dissecting their differential regulation in
the brain.
PMID- 28507508
TI - Improving Focal Photostimulation of Cortical Neurons with Pre-derived Wavefront
Correction.
AB - Recent progress in neuroscience to image and investigate brain function has been
made possible by impressive developments in optogenetic and opto-molecular tools.
Such research requires advances in optical techniques for the delivery of light
through brain tissue with high spatial resolution. The tissue causes distortions
to the wavefront of the incoming light which broadens the focus and consequently
reduces the intensity and degrades the resolution. Such effects are detrimental
in techniques requiring focal stimulation. Adaptive wavefront correction has been
demonstrated to compensate for these distortions. However, iterative derivation
of the corrective wavefront introduces time constraints that limit its
applicability to probe living cells. Here, we demonstrate that we can pre
determine and generalize a small set of Zernike modes to correct for aberrations
of the light propagating through specific brain regions. A priori identification
of a corrective wavefront is a direct and fast technique that improves the
quality of the focus without the need for iterative adaptive wavefront
correction. We verify our technique by measuring the efficiency of two-photon
photolysis of caged neurotransmitters along the dendrites of a whole-cell patched
neuron. Our results show that encoding the selected Zernike modes on the
excitation light can improve light propagation through brain slices of rats as
observed by the neuron's evoked excitatory post-synaptic potential in response to
localized focal uncaging at the spines of the neuron's dendrites.
PMID- 28507510
TI - Enhanced Axonal Extension of Subcortical Projection Neurons Isolated from Murine
Embryonic Cortex using Neuropilin-1.
AB - The cerebral cortical tissue of murine embryo and pluripotent stem cell (PSC)
derived neurons can survive in the brain and extend axons to the spinal cord. For
efficient cell integration to the corticospinal tract (CST) after
transplantation, the induction or selection of cortical motor neurons is
important. However, precise information about the appropriate cell population
remains unclear. To address this issue, we isolated cells expressing Neuropilin-1
(NRP1), a major axon guidance molecule receptor during the early developmental
stage, from E14.5 mouse embryonic frontal cortex by fluorescence-activated cell
sorting. Aggregates of NRP1+ cells gradually expressed subcortical projection
neuron markers, Ctip2 and VGluT1, and axon guidance molecule receptors, Robo1 and
deleted in colorectal calcinoma (Dcc), in vitro, suggesting that they contained
early-stage subcortical projection neurons. We transplanted NRP1+ cells into the
frontal cortex of P2 neonatal mice. Compared with grafts derived from NRP1- or
unsorted cells, those derived from NRP1+ cells extended a larger number of axons
to the spinal cord along the CST. Our data suggest that sorting NRP1+ cells from
the embryonic cerebral cortex enriches subcortical projection neurons to
reconstruct the CST.
PMID- 28507509
TI - Loss of Elp3 Impairs the Acetylation and Distribution of Connexin-43 in the
Developing Cerebral Cortex.
AB - The Elongator complex is required for proper development of the cerebral cortex.
Interfering with its activity in vivo delays the migration of postmitotic
projection neurons, at least through a defective alpha-tubulin acetylation.
However, this complex is already expressed by cortical progenitors where it may
regulate the early steps of migration by targeting additional proteins. Here we
report that connexin-43 (Cx43), which is strongly expressed by cortical
progenitors and whose depletion impairs projection neuron migration, requires
Elongator expression for its proper acetylation. Indeed, we show that Cx43
acetylation is reduced in the cortex of Elp3cKO embryos, as well as in a
neuroblastoma cell line depleted of Elp1 expression, suggesting that Cx43
acetylation requires Elongator in different cellular contexts. Moreover, we show
that histones deacetylase 6 (HDAC6) is a deacetylase of Cx43. Finally, we report
that acetylation of Cx43 regulates its membrane distribution in apical
progenitors of the cerebral cortex.
PMID- 28507507
TI - PINK1/Parkin-Dependent Mitochondrial Surveillance: From Pleiotropy to Parkinson's
Disease.
AB - Parkinson's disease (PD) is one of the most frequent neurodegenerative disease
caused by the preferential, progressive degeneration of the dopaminergic (DA)
neurons of the substantia nigra (SN) pars compacta. PD is characterized by a
multifaceted pathological process involving protein misfolding, mitochondrial
dysfunction, neuroinflammation and metabolism deregulation. The molecular
mechanisms governing the complex interplay between the different facets of this
process are still unknown. PARK2/Parkin and PARK6/PINK1, two genes responsible
for familial forms of PD, act as a ubiquitous core signaling pathway, coupling
mitochondrial stress to mitochondrial surveillance, by regulating mitochondrial
dynamics, the removal of damaged mitochondrial components by mitochondria-derived
vesicles, mitophagy, and mitochondrial biogenesis. Over the last decade,
PINK1/Parkin-dependent mitochondrial quality control emerged as a pleiotropic
regulatory pathway. Loss of its function impinges on a number of physiological
processes suspected to contribute to PD pathogenesis. Its role in the regulation
of innate immunity and inflammatory processes stands out, providing compelling
support to the contribution of non-cell-autonomous immune mechanisms in PD. In
this review, we illustrate the central role of this multifunctional pathway at
the crossroads between mitochondrial stress, neuroinflammation and metabolism. We
discuss how its dysfunction may contribute to PD pathogenesis and pinpoint major
unresolved questions in the field.
PMID- 28507511
TI - Distribution of ELOVL4 in the Developing and Adult Mouse Brain.
AB - ELOngation of Very Long chain fatty acids (ELOVL)-4 is essential for the
synthesis of very long chain-fatty acids (fatty acids with chain lengths >= 28
carbons). The functions of ELOVL4 and its very long-chain fatty acid products are
poorly understood at present. However, mutations in ELOVL4 cause
neurodevelopmental or neurodegenerative diseases that vary according to the
mutation and inheritance pattern. Heterozygous inheritance of different ELOVL4
mutations causes Stargardt-like Macular Dystrophy or Spinocerebellar Ataxia type
34. Homozygous inheritance of ELOVL4 mutations causes more severe disease
characterized by seizures, intellectual disability, ichthyosis, and premature
death. To better understand ELOVL4 and very long chain fatty acid function in the
brain, we examined ELOVL4 expression in the mouse brain between embryonic day 18
and postnatal day 60 by immunolabeling using ELOVL4 and other marker antibodies.
ELOVL4 was widely expressed in a region- and cell type-specific manner, and was
restricted to cell bodies, consistent with its known localization to endoplasmic
reticulum. ELOVL4 labeling was most prominent in gray matter, although labeling
also was present in some cells located in white matter. ELOVL4 was widely
expressed in the developing brain by embryonic day 18 and was especially
pronounced in regions underlying the lateral ventricles and other neurogenic
regions. The basal ganglia in particular showed intense ELOVL4 labeling at this
stage. In the postnatal brain, cerebral cortex, hippocampus, cerebellum,
thalamus, hypothalamus, midbrain, pons, and medulla all showed prominent ELOVL4
labeling, although ELOVL4 distribution was not uniform across all cells or
subnuclei within these regions. In contrast, the basal ganglia showed little
ELOVL4 labeling in the postnatal brain. Double labeling studies showed that
ELOVL4 was primarily expressed by neurons, although presumptive oligodendrocytes
located in white matter tracts also showed labeling. Little or no ELOVL4 labeling
was present in astrocytes or radial glial cells. These findings suggest that
ELOVL4 and its very long chain fatty acid products are important in many parts of
the brain and that they are particularly associated with neuronal function.
Specific roles for ELOVL4 and its products in oligodendrocytes and myelin and in
cellular proliferation, especially during development, are possible.
PMID- 28507512
TI - Changes in Dopamine Transmission in the Nucleus Accumbens Shell and Core during
Ethanol and Sucrose Self-Administration.
AB - Ethanol, like other substances of abuse, preferentially increases dopamine (DA)
transmission in the rat nucleus accumbens (NAc) following passive administration.
It remains unclear, however, whether ethanol also increases NAc DA transmission
following operant oral self-administration (SA). The NAc is made-up of a ventro
medial compartment, the shell and a dorso-lateral one, the core, where DA
transmission responds differentially following exposure to drugs of abuse.
Previous studies from our laboratory investigated changes in dialysate DA in the
NAc shell and core of rats responding for sucrose pellets and for drugs of abuse.
As a follow up to these studies, we recently investigated the changes in NAc
shell and core DA transmission associated to oral SA of a 10% ethanol solution.
For the purpose of comparison with literature studies utilizing sucrose + ethanol
solutions, we also investigated the changes in dialysate DA associated to SA of
20% sucrose and 10% ethanol + 20% sucrose solutions. Rats were trained to acquire
oral SA of the solutions under a Fixed Ratio 1 (FR1) schedule of nose-poking.
After training, rats were monitored by microdialysis on three consecutive days
under response contingent (active), reward omission (extinction trial) and
response non-contingent (passive) presentation of ethanol, sucrose or ethanol +
sucrose solutions. Active and passive ethanol administration produced a similar
increase in dialysate DA in the two NAc subdivisions, while under extinction
trial DA increased preferentially in the shell compared to the core. Conversely,
under sucrose SA and extinction DA increased exclusively in the shell. These
observations provide unequivocal evidence that oral SA of 10% ethanol increases
dialysate DA in the NAc, and also suggest that stimuli conditioned to ethanol
exposure contribute to the increase of dialysate DA observed in the NAc following
ethanol SA. Comparison between the pattern of DA changes detected in the NAc
subdivisions under sucrose and ethanol SA likewise suggests that the NAc shell
and core DA play different roles in sucrose as compared to ethanol reinforcement.
PMID- 28507514
TI - Markovian Analysis of the Sequential Behavior of the Spontaneous Spinal Cord
Dorsum Potentials Induced by Acute Nociceptive Stimulation in the Anesthetized
Cat.
AB - In a previous study we developed a Machine Learning procedure for the automatic
identification and classification of spontaneous cord dorsum potentials (CDPs).
This study further supported the proposal that in the anesthetized cat, the
spontaneous CDPs recorded from different lumbar spinal segments are generated by
a distributed network of dorsal horn neurons with structured (non-random)
patterns of functional connectivity and that these configurations can be changed
to other non-random and stable configurations after the noceptive stimulation
produced by the intradermic injection of capsaicin in the anesthetized cat. Here
we present a study showing that the sequence of identified forms of the
spontaneous CDPs follows a Markov chain of at least order one. That is, the
system has memory in the sense that the spontaneous activation of dorsal horn
neuronal ensembles producing the CDPs is not independent of the most recent
activity. We used this markovian property to build a procedure to identify
portions of signals as belonging to a specific functional state of connectivity
among the neuronal networks involved in the generation of the CDPs. We have
tested this procedure during acute nociceptive stimulation produced by the
intradermic injection of capsaicin in intact as well as spinalized preparations.
Altogether, our results indicate that CDP sequences cannot be generated by a
renewal stochastic process. Moreover, it is possible to describe some functional
features of activity in the cord dorsum by modeling the CDP sequences as
generated by a Markov order one stochastic process. Finally, these Markov models
make possible to determine the functional state which produced a CDP sequence.
The proposed identification procedures appear to be useful for the analysis of
the sequential behavior of the ongoing CDPs recorded from different spinal
segments in response to a variety of experimental procedures including the
changes produced by acute nociceptive stimulation. They are envisaged as a useful
tool to examine alterations of the patterns of functional connectivity between
dorsal horn neurons under normal and different pathological conditions, an issue
of potential clinical concern.
PMID- 28507513
TI - Appetitive Olfactory Learning and Long-Term Associative Memory in Caenorhabditis
elegans.
AB - Because of the relative simplicity of its nervous system, Caenorhabditis elegans
is a useful model organism to study learning and memory at cellular and molecular
levels. For appetitive conditioning in C. elegans, food has exclusively been used
as an unconditioned stimulus (US). It may be difficult to analyze neuronal
circuits for associative memory since food is a multimodal combination of
olfactory, gustatory, and mechanical stimuli. Here, we report classical
appetitive conditioning and associative memory in C. elegans, using 1-nonanol as
a conditioned stimulus (CS), and potassium chloride (KCl) as a US. Before
conditioning, C. elegans innately avoided 1-nonanol, an aversive olfactory
stimulus, and was attracted by KCl, an appetitive gustatory stimulus, on assay
agar plates. Both massed training without an intertrial interval (ITI) and spaced
training with a 10-min ITI induced significant levels of memory of association
regarding the two chemicals. Memory induced by massed training decayed within 6
h, while that induced by spaced training was retained for more than 6 h. Animals
treated with inhibitors of transcription or translation formed the memory induced
by spaced training less efficiently than untreated animals, whereas the memory
induced by massed training was not significantly affected by such treatments. By
definition, therefore, memories induced by massed training and spaced training
are classified as short-term memory (STM) and long-term memory (LTM),
respectively. When animals conditioned by spaced training were exposed to 1
nonanol alone, their learning index was lower than that of untreated animals,
suggesting that extinction learning occurs in C. elegans. In support of these
results, C. elegans mutants defective in nmr-1, encoding an NMDA receptor
subunit, formed both STM and LTM less efficiently than wild-type animals, while
mutations in crh-1, encoding a ubiquitous transcription factor CREB required for
memory consolidation, affected LTM, but not STM. The paradigm established in the
present study should allow us to elucidate neuronal circuit plasticity for
appetitive learning and memory in C. elegans.
PMID- 28507515
TI - Reusable Client-Side JavaScript Modules for Immersive Web-Based Real-Time
Collaborative Neuroimage Visualization.
AB - In this paper we present a web-based software solution to the problem of
implementing real-time collaborative neuroimage visualization. In both clinical
and research settings, simple and powerful access to imaging technologies across
multiple devices is becoming increasingly useful. Prior technical solutions have
used a server-side rendering and push-to-client model wherein only the server has
the full image dataset. We propose a rich client solution in which each client
has all the data and uses the Google Drive Realtime API for state
synchronization. We have developed a small set of reusable client-side object
oriented JavaScript modules that make use of the XTK toolkit, a popular open
source JavaScript library also developed by our team, for the in-browser
rendering and visualization of brain image volumes. Efficient realtime
communication among the remote instances is achieved by using just a small JSON
object, comprising a representation of the XTK image renderers' state, as the
Google Drive Realtime collaborative data model. The developed open-source
JavaScript modules have already been instantiated in a web-app called MedView, a
distributed collaborative neuroimage visualization application that is delivered
to the users over the web without requiring the installation of any extra
software or browser plugin. This responsive application allows multiple
physically distant physicians or researchers to cooperate in real time to reach a
diagnosis or scientific conclusion. It also serves as a proof of concept for the
capabilities of the presented technological solution.
PMID- 28507518
TI - Beneficial Effects of Sulforaphane Treatment in Alzheimer's Disease May Be
Mediated through Reduced HDAC1/3 and Increased P75NTR Expression.
AB - Alzheimer's disease is an irreversible, progressive neurodegenerative disorder.
The accumulation of Abeta in the brain is thought to play a causative role in the
development of cognitive dysfunction in Alzheimer's disease. The p75 neurotrophin
receptor is of great importance to protect against the Abeta burden and its
expression is regulated by histone acetylation. This study investigated whether
the phytochemical sulforaphane, a pan-histone deacetylase inhibitor, up-regulates
the p75 neurotrophin receptor expression via affecting histone acetylation in
protection against Alzheimer's disease. We found that sulforaphane ameliorated
behavioral cognitive impairments and attenuated brain Abeta burden in Alzheimer's
disease model mice. Additionally, sulforaphane reduced the expression of histone
deacetylase1, 2, and 3, up-regulated p75 neurotrophin receptor, and increased
levels of acetylated histone 3 lysine 9 and acetylated histone 4 lysine 12 in the
cerebral cortex of Alzheimer's disease model mice as well as in Abeta-exposed SH
SY5Y cells. Furthermore, silencing of histone deacetylase1 and 3, but not histone
deacetylase2, gene expression with small interfering RNA caused up-regulation of
p75 neurotrophin receptor in SH-SY5Y cells. In conclusion, this study
demonstrates that sulforaphane can ameliorate neurobehavioral deficits and reduce
the Abeta burden in Alzheimer's disease model mice, and the mechanism underlying
these effects may be associated with up-regulation of p75 neurotrophin receptor
mediated, apparently at least in part, via reducing the expression of histone
deacetylase1 and 3.
PMID- 28507517
TI - The Role of Unfolded Protein Response and Mitogen-Activated Protein Kinase
Signaling in Neurodegenerative Diseases with Special Focus on Prion Diseases.
AB - Prion diseases are neurodegenerative pathologies characterized by the
accumulation of a protease-resistant form of the cellular prion protein named
prion protein scrapie (PrPSc) in the brain. PrPSc accumulation in the endoplasmic
reticulum (ER) result in a dysregulated calcium (Ca2+) homeostasis and subsequent
initiation of unfolded protein response (UPR) leading to neuronal dysfunction and
apoptosis. The molecular mechanisms for the transition between adaptation to ER
stress and ER stress-induced apoptosis are still unclear. Mitogen-activated
protein kinases (MAPKs) are serine/threonine protein kinases that rule the
signaling of many extracellular stimuli from plasma membrane to the nucleus.
However the identification of numerous points of cross talk between the UPR and
MAPK signaling pathways may contribute to our understanding of the consequences
of ER stress in prion diseases. Indeed the MAPK signaling network is known to
regulate cell cycle progression and cell survival or death responses following a
variety of stresses including misfolded protein response stress. In this article,
we review the UPR signaling in prion diseases and discuss the triad of MAPK
signaling pathways. We also describe the role played by MAPK signaling cascades
in Alzheimer's (AD) and Parkinson's disease (PD). We will also overview the
mechanisms of cell death and the role of MAPK signaling in prion disease
progression and highlight potential avenues for therapeutic intervention.
PMID- 28507519
TI - Vasorelaxing Action of the Kynurenine Metabolite, Xanthurenic Acid: The Missing
Link in Endotoxin-Induced Hypotension?
AB - The kynurenine pathway of tryptophan metabolism is activated by pro-inflammatory
cytokines. L-kynurenine, an upstream metabolite of the pathway, acts as a
putative endothelium-derived relaxing factor, and has been hypothesized to play a
causative role in the pathophysiology of inflammation-induced hypotension. Here,
we show that xanthurenic acid (XA), the transamination product of 3
hydroxykynurenine, is more efficacious than L-kynurenine in causing relaxation of
a resistance artery, but fails to relax pre-contracted aortic rings. In the
mesenteric artery, XA enhanced activating phosphorylation of endothelial nitric
oxide synthase (NOS), and the relaxing action of XA was abrogated by
pharmacological inhibition of NOS and endothelial-derived hyperpolarizing factor.
Systemic injection of XA reduced blood pressure in mice, and serum levels of XA
increased by several fold in response to a pulse with the endotoxin,
lipopolysaccharide (LPS). LPS-induced hypotension in mice was prevented by pre
treatment with the kynurenine monooxygenase (KMO) inhibitor, Ro-618048, which
lowered serum levels of XA but enhanced serum levels of L-kynurenine. UPF 648,
another KMO inhibitor, could also abrogate LPS-induced hypotension. Our data
identify XA as a novel vasoactive compound and suggest that formation of XA is a
key event in the pathophysiology of inflammation-induced hypotension.
PMID- 28507520
TI - In Vitro and In Silico Antidiabetic and Antimicrobial Evaluation of Constituents
from Kickxia ramosissima (Nanorrhinum ramosissimum).
AB - Background and Aims:Kickxia ramosissima (Wall.) Janch (or Nanorrhinum
ramosissimum (Wall.) Betsche is a well-known medicinal plant in Pakistan that is
traditionally used in diabetic and inflammatory conditions. Because little
information is available on its phytochemical composition, a range of
constituents were isolated and evaluated in vitro in assays related to the
traditional use. Methods: Dried whole plant material was extracted and
chromatographically fractionated. Isolated constituents were evaluated in silico
and in vitro in assays related to the traditional use against diabetes
(inhibition of alpha-glucosidase activity; inhibition of advanced glycation
endproducts) and in inflammatory conditions (inhibition of AAPH induced linoleic
acid peroxidation, inhibition of 15-LOX, antimicrobial activity). Results:
Phytochemical analysis of the extracts and fractions led to isolation of 7
compounds, including the iridoids kickxiasine (being a new compound),
mussaenosidic acid, mussaenoside and linarioside; the flavonoids pectolinarigenin
and pectolinarin; and 4-hydroxy-benzoic acid methyl ester. The iridoids showed
weak antiglycation activity. The flavonoids, however, showed interesting results
as pectolinarigenin was highly active compared to pectolinarin. In the alpha
glucosidase inhibition assay, only weak activity was observed for the iridoids.
However, the flavonoid pectolinarigenin showed good activity, followed by
pectolinarin. In the 15-LOX experiment, moderate inhibition was recorded for most
compounds, the iridoids mussaenosidic acid and mussaenoside being the most
active. In the AAPH assay, weak or no inhibition was recorded for all compounds.
The in silico assays for the alpha-glucosidase and 15-LOX assays confirmed the
results of respective in vitro assays. Pectolinarigenin showed moderate
antimicrobial activity against Staphylococcus aureus, Plasmodium falciparum K1,
and Trypanosoma cruzi, but it was not cytotoxic on a human MRC-5 cell line.
Conclusion: Our findings may in part contribute to explain the traditional use of
K. ramosissima.
PMID- 28507516
TI - Body-Brain Connections: The Effects of Obesity and Behavioral Interventions on
Neurocognitive Aging.
AB - Obesity is a growing public health problem in the United States, particularly in
middle-aged and older adults. Although the key factors leading to a population
increase in body weight are still under investigation, there is evidence that
certain behavioral interventions can mitigate the negative cognitive and brain
("neurocognitive") health consequences of obesity. The two primary behaviors most
often targeted for weight loss are caloric intake and physical activity. These
behaviors might have independent, as well as overlapping/synergistic effects on
neurocognitive health. To date obesity is often described independently from
behavioral interventions in regards to neurocognitive outcomes, yet there is
conceptual and mechanistic overlap between these constructs. This review
summarizes evidence linking obesity and modifiable behaviors, such as physical
activity and diet, with brain morphology (e.g., gray and white matter volume and
integrity), brain function (e.g., functional activation and connectivity), and
cognitive function across the adult lifespan. In particular, we review evidence
bearing on the following question: Are associations between obesity and brain
health in aging adults modifiable by behavioral interventions?
PMID- 28507521
TI - Prime Time Light Exposures Do Not Seem to Improve Maximal Physical Performance in
Male Elite Athletes, but Enhance End-Spurt Performance.
AB - Many sports competitions take place during television prime time, a time of the
day when many athletes have already exceeded their time of peak performance. We
assessed the effect of different light exposure modalities on physical
performance and melatonin levels in athletes during prime time. Seventy-two
young, male elite athletes with a median (interquartile range) age of 23 (21; 29)
years and maximum oxygen uptake (VO2max) of 63 (58; 66) ml/kg/min were randomly
assigned to three different light exposure groups: bright light (BRIGHT), blue
monochromatic light (BLUE), and control light (CONTROL). Each light exposure
lasted 60 min and was scheduled to start 17 h after each individual's midpoint of
sleep (median time: 9:17 pm). Immediately after light exposure, a 12-min time
trial was performed on a bicycle ergometer. The test supervisor and participants
were blinded to the light condition each participant was exposed to. The median
received light intensities and peak wavelengths (photopic lx/nm) measured at eye
level were 1319/545 in BRIGHT, 203/469 in BLUE, and 115/545 in CONTROL. In a
multivariate analysis adjusted for individual VO2max, total work performed in 12
min did not significantly differ between the three groups. The amount of exposure
to non-image forming light was positively associated with the performance gain
during the time trial, defined as the ratio of the work performed in the first
and last minute of the time trial, and with stronger melatonin suppression.
Specifically, a tenfold increase in the exposure to melanopic light was
associated with a performance gain of 8.0% (95% confidence interval: 2.6, 13.3; P
= 0.004) and a melatonin decrease of -0.9 pg/ml (95% confidence interval: -1.5,
0.3; P = 0.006). Exposure to bright or blue light did not significantly improve
maximum cycling performance in a 12-min all-out time trial. However, it is
noteworthy that the estimated difference of 4.1 kJ between BRIGHT and CONTROL
might represent an important performance advantage justifying further studies. In
conclusion, we report novel evidence that evening light exposure, which strongly
impacts the human circadian timing system, enables elite athletes to better
maintain performance across a 12-min cycling time trial.
PMID- 28507522
TI - Nicotine Acutely Enhances Reinforcement from Non-Drug Rewards in Humans.
AB - Preclinical research documents that, aside from the primary and secondary
reinforcing effects of nicotine intake itself, nicotine also acutely enhances the
reinforcing efficacy of non-drug reinforcers ("rewards"). Study of these effects
in humans has largely been overlooked, but very recent findings suggest they may
have clinical implications for more fully understanding the persistence of
tobacco dependence. This overview first outlines the topic and notes some recent
human studies indirectly addressing nicotine effects on related responses (e.g.,
subjective ratings), explaining why those findings do not directly confirm
enhancement of behavioral reinforcement per se due to nicotine. Then, the
methodology used in the subsequently presented studies is described,
demonstrating how those studies specifically did demonstrate enhancement of
reinforced responding for non-drug rewards. The main section focuses on the
limited controlled research to date directly assessing nicotine's acute
reinforcement-enhancing effects in humans, particularly as it relates to
reinforced behavioral responding for non-drug rewards in non-human animal models.
After detailing those few existing human studies, we address potential
consequences of these effects for dependence and tobacco cessation efforts and
then suggest directions for future research. This research indicates that
nicotine per se increases responding in humans that is reinforced by some rewards
(auditory stimuli via music, visual stimuli via video), but perhaps not by others
(e.g., money). These reinforcement-enhancing effects in smokers are not due to
dependence or withdrawal relief and can be restored by a small amount of nicotine
(similar to a smoking lapse), including from e-cigarettes, a non-tobacco nicotine
product. Future clinical research should examine factors determining which types
of rewards are (or are not) enhanced by nicotine, consequences of the loss of
these nicotine effects after quitting smoking, potential individual differences
in these effects, and the possibility that nicotine via nicotine replacement
therapy and non-nicotine quit medications may attenuate loss of these effects
upon quitting. Further study with humans of nicotine's reinforcement-enhancing
effects may provide a more complete understanding of smoking persistence and
added mechanisms of cessation medication efficacy.
PMID- 28507523
TI - Autism Spectrum Disorders and Schizophrenia Spectrum Disorders:
Excitation/Inhibition Imbalance and Developmental Trajectories.
AB - Autism spectrum disorders (ASD) and schizophrenia spectrum disorders (SSD) share
clinical and genetic components that have long been recognized. The two disorders
co-occur more frequently than would be predicted by their respective prevalence,
suggesting that a complex, multifactor association is involved. However, DSM-5
maintains the distinction between ASD, with core social and communication
impairments, and SSD, including schizophrenia (SCZ), with hallucinations,
delusions, and thought disorder as essential features. ASD and SSD have common
biological underpinnings that may emerge early in development and unfold over
time. One of the hypotheses supporting the similarities in the social and
cognitive disturbances of ASD and SSD relates to abnormalities in the ratio of
excitatory to inhibitory cortical activity (E/I imbalance). E/I imbalance in
neurodevelopmental disorders could be the consequence of abnormalities in genes
coding for glutamatergic and GABAergic receptors or synaptic proteins followed by
system derangements. SSD and ASD have been characterized as polygenic disorders
in which to the onset and progression of disease is triggered by interactions
among multiple genes. Mammalian target of rapamycin signaling is under intense
investigation as a convergent altered pathway in the two spectrum disorders.
Current understanding of shared and divergent patterns between ASD and SSD from
molecular to clinical aspects is still incomplete and may be implemented by the
research domain criteria approach.
PMID- 28507525
TI - Modernizing Relationship Therapy through Social Thermoregulation Theory:
Evidence, Hypotheses, and Explorations.
AB - In the present article the authors propose to modernize relationship therapy by
integrating novel sensor and actuator technologies that can help optimize
people's thermoregulation, especially as they pertain to social contexts.
Specifically, they propose to integrate Social Thermoregulation Theory (IJzerman
et al., 2015a; IJzerman and Hogerzeil, 2017) into Emotionally Focused Therapy by
first doing exploratory research during couples' therapy, followed by Randomized
Clinical Trials (RCTs). The authors thus suggest crafting a Social
Thermoregulation Therapy (STT) as enhancement to existing relationship therapies.
The authors outline what is known and not known in terms of social
thermoregulatory mechanisms, what kind of data collection and analyses are
necessary to better understand social thermoregulatory mechanisms to craft
interventions, and stress the need to conduct RCTs prior to implementation. They
further warn against too hastily applying these theoretical perspectives. The
article concludes by outlining why STT is the way forward in improving
relationship functioning.
PMID- 28507524
TI - Changing What You See by Changing What You Know: The Role of Attention.
AB - Attending is a cognitive process that incorporates a person's knowledge, goals,
and expectations. What we perceive when we attend to one thing is different from
what we perceive when we attend to something else. Yet, it is often argued that
attentional effects do not count as evidence that perception is influenced by
cognition. I investigate two arguments often given to justify excluding
attention. The first is arguing that attention is a post-perceptual process
reflecting selection between fully constructed perceptual representations. The
second is arguing that attention as a pre-perceptual process that simply changes
the input to encapsulated perceptual systems. Both of these arguments are highly
problematic. Although some attentional effects can indeed be construed as post
perceptual, others operate by changing perceptual content across the entire
visual hierarchy. Although there is a natural analogy between spatial attention
and a change of input, the analogy falls apart when we consider other forms of
attention. After dispelling these arguments, I make a case for thinking of
attention not as a confound, but as one of the mechanisms by which cognitive
states affect perception by going through cases in which the same or similar
visual inputs are perceived differently depending on the observer's cognitive
state, and instances where cuing an observer using language affects what one
sees. Lastly, I provide two compelling counter-examples to the critique that
although cognitive influences on perception can be demonstrated in the
laboratory, it is impossible to really experience them for oneself in a
phenomenologically compelling way. Taken together, the current evidence strongly
supports the thesis that what we know routinely influences what we see, that the
same sensory input can be perceived differently depending on the current
cognitive state of the viewer, and that phenomenologically salient demonstrations
are possible if certain conditions are met.
PMID- 28507527
TI - Perceived Insider Status and Feedback Reactions: A Dual Path of Feedback
Motivation Attribution.
AB - Many studies have evaluated how the characteristics of feedback receiver,
feedback deliverer and feedback information influence psychological feedback
reactions of the feedback receiver while largely neglecting that feedback
intervention is a kind of social interaction process. To address this issue, this
study proposes that employees' perceived insider status (PIS), as a kind of
employee-organization relationship, could also influence employees' reactions to
supervisory feedback. In particular, this study investigates the influence of PIS
focusing on affective and cognitive feedback reactions, namely feedback
satisfaction and feedback utility. Surveys were conducted in a machinery
manufacturing company in the Guangdong province of China. Samples were collected
from 192 employees. Data analysis demonstrated that PIS and feedback utility
possessed a U-shaped relationship, whereas PIS and feedback satisfaction
exhibited positively linear relationships. The analysis identified two kinds of
mediating mechanisms related to feedback satisfaction and feedback utility.
Internal feedback motivation attribution partially mediated the relationship
between PIS and feedback satisfaction but failed to do the same with respect to
the relationship between PIS and feedback utility. In contrast, external feedback
motivation attribution partially mediated the relationship between PIS and
feedback utility while failing to mediate the relationship between PIS and
feedback satisfaction. Theoretical contributions and practical implications of
the findings are discussed at the end of the paper.
PMID- 28507526
TI - Behavioral and Neural Manifestations of Reward Memory in Carriers of Low
Expressing versus High-Expressing Genetic Variants of the Dopamine D2 Receptor.
AB - Dopamine is critically important in the neural manifestation of motivated
behavior, and alterations in the human dopaminergic system have been implicated
in the etiology of motivation-related psychiatric disorders, most prominently
addiction. Patients with chronic addiction exhibit reduced dopamine D2 receptor
(DRD2) availability in the striatum, and the DRD2 TaqIA (rs1800497) and C957T
(rs6277) genetic polymorphisms have previously been linked to individual
differences in striatal dopamine metabolism and clinical risk for alcohol and
nicotine dependence. Here, we investigated the hypothesis that the variants of
these polymorphisms would show increased reward-related memory formation, which
has previously been shown to jointly engage the mesolimbic dopaminergic system
and the hippocampus, as a potential intermediate phenotype for addiction memory.
To this end, we performed functional magnetic resonance imaging (fMRI) in 62
young, healthy individuals genotyped for DRD2 TaqIA and C957T variants.
Participants performed an incentive delay task, followed by a recognition memory
task 24 h later. We observed effects of both genotypes on the overall recognition
performance with carriers of low-expressing variants, namely TaqIA A1 carriers
and C957T C homozygotes, showing better performance than the other genotype
groups. In addition to the better memory performance, C957T C homozygotes also
exhibited a response bias for cues predicting monetary reward. At the neural
level, the C957T polymorphism was associated with a genotype-related modulation
of right hippocampal and striatal fMRI responses predictive of subsequent
recognition confidence for reward-predicting items. Our results indicate that
genetic variations associated with DRD2 expression affect explicit memory,
specifically for rewarded stimuli. We suggest that the relatively better memory
for rewarded stimuli in carriers of low-expressing DRD2 variants may reflect an
intermediate phenotype of addiction memory.
PMID- 28507528
TI - Cognitive Impairments in Occupational Burnout - Error Processing and Its Indices
of Reactive and Proactive Control.
AB - The presented study refers to cognitive aspects of burnout as the effects of long
term work-related stress. The purpose of the study was to investigate
electrophysiological correlates of burnout to explain the mechanisms of the core
burnout symptoms: exhaustion and depersonalization/cynicism. The analyzed error
related electrophysiological markers shed light on impaired cognitive mechanisms
and the specific changes in information-processing in burnout. In the EEG study
design (N = 80), two components of error-related potential (ERP), error-related
negativity (ERN), and error positivity (Pe), were analyzed. In the non-clinical
burnout group (N = 40), a significant increase in ERN amplitude and a decrease in
Pe amplitude were observed compared to controls (N = 40). Enhanced error
detection, indexed by increased ERN amplitude, and diminished response
monitoring, indexed by decreased Pe amplitude, reveal emerging cognitive problems
in the non-clinical burnout group. Cognitive impairments in burnout subjects
relate to both reactive and unconscious (ERN) and proactive and conscious (Pe)
aspects of error processing. The results indicate a stronger 'reactive control
mode' that can deplete resources for proactive control and the ability to
actively maintain goals. The analysis refers to error processing and specific
task demands, thus should not be extended to cognitive processes in general. The
characteristics of ERP patterns in burnout resemble psychophysiological indexes
of anxiety (increased ERN) and depressive symptoms (decreased Pe), showing to
some extent an overlapping effect of burnout and related symptoms and disorders.
The results support the scarce existing data on the psychobiological nature of
burnout, while extending and specifying its cognitive characteristics.
PMID- 28507529
TI - Parkinson Disease: An Evolutionary Perspective.
AB - There are two central premises to this evolutionary view of Parkinson disease
(PD). First, PD is a specific human disease. Second, the prevalence of PD has
increased over the course of human history. Several lines of evidence may explain
why PD appears to be restricted to the human species. The major manifestations of
PD are the consequence of degeneration in the dopamine-synthesizing neurons of
the mesostriatal neuronal pathway. It is of note the enormous expansion of the
human dopamine mesencephalic neurons onto the striatum compared with other
mammals. Hence, an evolutionary bottle neck was reached with the expansion of the
massive nigrostriatal axonal arborization. This peculiar nigral overload may
partly explain the selective fragility of the human dopaminergic mesencephalic
neurotransmission and the unique presence of PD in humans. On the other hand,
several facts may explain the increasing prevalence of PD over the centuries. The
apparently low prevalence of PD before the twentieth century may be related to
the shorter life expectancy and survival compared to present times. In addition,
changes in lifestyle over the course of human history might also account for the
increasing burden of PD. Our hunter-gatherers ancestors invested large energy
expenditure on a daily basis, a prototypical physical way of life for which our
genome remains adapted. Technological advances have led to a dramatic reduction
of physical exercise. Since the brain release of neurotrophic factors (including
brain-derived neurotrophic factor) is partially exercise related, the marked
reduction in exercise may contribute to the increasing prevalence of PD.
PMID- 28507530
TI - Brain-Derived Neurotrophic Factor Val66Met Gene Polymorphism Impacts on Migraine
Susceptibility: A Meta-analysis of Case-Control Studies.
AB - Inconclusive results have been reported in studies investigating the association
between the brain-derived neurotrophic factor (BDNF) rs6265 polymorphism and
migraine. In the present study, we conducted a systematic review and meta
analysis on the published data in order to quantitatively estimate the
relationship between rs6265 and migraine susceptibility. A comprehensive search
was performed through PubMed, Web of Knowledge, and Cochrane databases up to
October 2016. The pooled odds ratio (OR) with the corresponding 95% confidence
interval (CI) was calculated to estimate the strength of the association with
rs6265 under an additive, dominant, or recessive model of inheritance. A total of
five studies including 1,442 cases and 1,880 controls were identified for the
meta-analysis. The pooled data showed an increased risk of migraine for the
allelic (OR: 1.17, 95% CI: 1.03-1.34, p = 0.014) or the dominant model of rs6265
(OR: 1.22, 95% CI: 1.05-1.41, p = 0.011). Statistical significance of rs6265 was
lost when one single study was excluded from the analysis (dominant OR: 1.17, 95%
CI: 1.00-1.38, p = 0.054; allelic OR: 1.14, 95% CI: 0.99-1.31, p = 0.067),
suggesting lack of robustness of pooled estimates. When stratified by migraine
type, a similar trend of association was detected with both MA and MO, but a
statistically significant association of rs6265 was reached only with the MA
subtype in the dominant model (OR: 1.22, 95% CI: 1.00-1.47, p = 0.047). The
present meta-analysis supports that BDNF rs6265 may act as a genetic
susceptibility factor for migraine. Nevertheless, large-scale studies are
required to confirm our findings and to assess potential modifiers of the
relationship between rs6265 and migraine.
PMID- 28507531
TI - Noradrenergic Activation of Hypoglossal Nucleus Modulates the Central Regulation
of Genioglossus in Chronic Intermittent Hypoxic Rats.
AB - Neuromuscular compensation of the genioglossus muscle can be induced by chronic
intermittent hypoxia (CIH) in obstructive sleep apnea to maintain upper airway
stability. Noradrenergic activation of hypoglossal nucleus plays a critical role
in the central control of the genioglossus. However, it remains unknown whether
norepinephrine takes part in the central regulation of the genioglossus during
CIH. Adult male Wistar rats (n = 32) were studied to explore the influence of
noradrenergic activation of hypoglossal nucleus on the central control of the
genioglossus at different stages of CIH. The rats were divided into four groups:
normal control or normoxic (NO) group, CIH group, CIH + normal saline (NS) group,
and CIH + prazosin (PZ, alpha1-adrenergic antagonist) group. PZ (0.2 mM, 60 nl)
and NS (0.9%, 60 nl) were microinjected into the hypoglossal nucleus. The
responses of the genioglossus corticomotor area to transcranial magnetic
stimulation (TMS) were recorded on the 1st, 7th, 14th, and 21st day of CIH. The
CIH group showed significantly shorter TMS latencies on days 1, 7, and 14 (3.85
+/- 0.37 vs. 4.58 +/- 0.42, 3.93 +/- 0.17 vs. 4.49 +/- 0.55, 3.79 +/- 0.38 vs.
4.39 +/- 0.30 ms, P < 0.05), and higher TMS amplitudes on day 1 (2.74 +/- 0.87
vs. 1.60 +/- 0.52 mV, P < 0.05) of CIH than the NO group. Compared to the CIH +
NS group, the CIH + PZ group showed decreased TMS responses (longer latencies and
lower amplitudes) only on the 14th day of CIH (3.99 +/- 0.28 vs. 4.61 +/- 0.48
ms, 2.51 +/- 0.67 vs. 1.18 +/- 0.62 mV, P < 0.05). These results indicated that
noradrenergic activation of the hypoglossal nucleus played a role in the central
compensation of genioglossus through alpha1-adrenoceptor on the 14th day of CIH.
PMID- 28507532
TI - Spectral Domain-Optical Coherence Tomography As a New Diagnostic Marker for
Idiopathic Normal Pressure Hydrocephalus.
AB - PURPOSE: Characterized by a progressive onset of gait disturbances, dementia, and
urinary incontinence, idiopathic normal pressure hydrocephalus (iNPH) is
considered a rare, but under-diagnosed disease. Non-invasive diagnostic markers
are still insufficient to enable the diagnosis of iNPH with certainty and yet
early treatment with ventriculoperitoneal (VP) shunting can reverse symptoms and
stop disease progression. Vascular circulation abnormalities in iNPH may be
reflected by changes in subfoveal and peripapillary choroidal thickness (PPChT).
This study uses spectral domain-optical coherence tomography (SD-OCT)-based
measures of retinal and choroidal thickness to test this hypothesis and to assess
ophthalmological non-invasive markers for iNPH. METHODS: Twelve patients who
displayed neurological and neuroradiological characteristics of iNPH were subject
to a full ophthalmological examination including enhanced depth imaging (EDI) SD
OCT. Of the 12 included iNPH patients, 6 had undergone VP shunting with
beneficial outcome. Parameters studied with EDI SD-OCT were macular retinal
thickness (MT), subfoveal choroidal thickness (SFChT), retinal nerve fiber layer
thickness (RNFL), and PPChT. Results were compared with 13 healthy, age-matched
controls. RESULTS: Macular thickness and RNFL and MT values of iNPH patients did
not reflect atrophy. Non-shunted iNPH patients showed significantly lowered
median PPChT and SFChT values compared to healthy controls. Shunted iNPH patients
displayed a significantly higher median PPChT and SFChT compared to non-shunted
iNPH patients. SFChT and PPChT values in shunted patients were not significantly
different to values in healthy controls. CONCLUSION: Although limited by small
sample size, SD-OCT measures in this study reveal significant changes of
choroidal thickness and support the hypothesis of choroidal susceptibility to
hemodynamic alterations in iNPH. Non-shunted iNPH patients in this study show
choroidal thinning in combination with normal RNFL and MT values. In addition to
neurological and neuroradiological exams, this pattern may aid in the challenging
diagnosis of iNPH.
PMID- 28507535
TI - Bioreactor Scalability: Laboratory-Scale Bioreactor Design Influences
Performance, Ecology, and Community Physiology in Expanded Granular Sludge Bed
Bioreactors.
AB - Studies investigating the feasibility of new, or improved, biotechnologies, such
as wastewater treatment digesters, inevitably start with laboratory-scale trials.
However, it is rarely determined whether laboratory-scale results reflect full
scale performance or microbial ecology. The Expanded Granular Sludge Bed (EGSB)
bioreactor, which is a high-rate anaerobic digester configuration, was used as a
model to address that knowledge gap in this study. Two laboratory-scale
idealizations of the EGSB-a one-dimensional and a three- dimensional scale-down
of a full-scale design-were built and operated in triplicate under near-identical
conditions to a full-scale EGSB. The laboratory-scale bioreactors were seeded
using biomass obtained from the full-scale bioreactor, and, spent water from the
distillation of whisky from maize was applied as substrate at both scales. Over
70 days, bioreactor performance, microbial ecology, and microbial community
physiology were monitored at various depths in the sludge-beds using 16S rRNA
gene sequencing (V4 region), specific methanogenic activity (SMA) assays, and a
range of physical and chemical monitoring methods. SMA assays indicated dominance
of the hydrogenotrophic pathway at full-scale whilst a more balanced activity
profile developed during the laboratory-scale trials. At each scale,
Methanobacterium was the dominant methanogenic genus present. Bioreactor
performance overall was better at laboratory-scale than full-scale. We observed
that bioreactor design at laboratory-scale significantly influenced spatial
distribution of microbial community physiology and taxonomy in the bioreactor
sludge-bed, with 1-D bioreactor types promoting stratification of each. In the 1
D laboratory bioreactors, increased abundance of Firmicutes was associated with
both granule position in the sludge bed and increased activity against acetate
and ethanol as substrates. We further observed that stratification in the sludge
bed in 1-D laboratory-scale bioreactors was associated with increased richness in
the underlying microbial community at species (OTU) level and improved overall
performance.
PMID- 28507534
TI - Stress and Alterations in Bones: An Interdisciplinary Perspective.
AB - Decades of research have demonstrated that physical stress (PS) stimulates bone
remodeling and affects bone structure and function through complex
mechanotransduction mechanisms. Recent research has laid ground to the hypothesis
that mental stress (MS) also influences bone biology, eventually leading to
osteoporosis and increased bone fracture risk. These effects are likely exerted
by modulation of hypothalamic-pituitary-adrenal axis activity, resulting in an
altered release of growth hormones, glucocorticoids and cytokines, as
demonstrated in human and animal studies. Furthermore, molecular cross talk
between mental and PS is thought to exist, with either synergistic or
preventative effects on bone disease progression depending on the characteristics
of the applied stressor. This mini review will explain the emerging concept of MS
as an important player in bone adaptation and its potential cross talk with PS by
summarizing the current state of knowledge, highlighting newly evolving notions
(such as intergenerational transmission of stress and its epigenetic
modifications affecting bone) and proposing new research directions.
PMID- 28507533
TI - Cytokine Receptor Endocytosis: New Kinase Activity-Dependent and -Independent
Roles of PI3K.
AB - Type I and II cytokine receptors are cell surface sensors that bind cytokines in
the extracellular environment and initiate intracellular signaling to control
processes such as hematopoiesis, immune function, and cellular growth and
development. One key mechanism that regulates signaling from cytokine receptors
is through receptor endocytosis. In this mini-review, we describe recent advances
in endocytic regulations of cytokine receptors, focusing on new paradigms by
which PI3K controls receptor endocytosis through both kinase activity-dependent
and -independent mechanisms. These advances underscore the notion that the p85
regulatory subunit of PI3K has functions beyond regulating PI3K kinase activity,
and that PI3K plays both positive and negative roles in receptor signaling. On
the one hand, the PI3K/Akt pathway controls various aspects downstream of
cytokine receptors. On the other hand, it stimulates receptor endocytosis and
downregulation, thus contributing to signaling attenuation.
PMID- 28507536
TI - Temporal Genomic Phylogeny Reconstruction Indicates a Geospatial Transmission
Path of Salmonella Cerro in the United States and a Clade-Specific Loss of
Hydrogen Sulfide Production.
AB - Salmonella Cerro has become one of the most prevalent Salmonella serotypes
isolated from dairy cattle in several U.S. states, including New York where it
represented 36% of all Salmonella isolates of bovine origin in 2015. This
serotype is commonly isolated from dairy cattle with clinical signs of
salmonellosis, including diarrhea and fever, although it has also been identified
in herds without evidence of clinical disease or decreased production. To better
understand the transmission patterns and drivers of its geographic spread, we
have studied the genomic similarity and microevolution of S. Cerro isolates from
the northeast U.S. and Texas. Eighty-three out of 86 isolates were confirmed as
multilocus sequence type 367. We identified core genome SNPs in 57 upstate New
York (NY), 2 Pennsylvania (PA), and 27 Texas S. Cerro isolates from dairy cattle,
farm environments, raw milk, and one human clinical case and used them to
construct a tip-dated phylogeny. S. Cerro isolates clustered in three distinct
clades, including (i) clade I (n = 3; 2013) comprising isolates from northwest
Texas (NTX), (ii) clade II (n = 14; 2009-2011, 2014) comprising isolates from NY,
and (iii) clade III comprising isolates from NY, PA, and central Texas (CTX) in
subclade IIIa (n = 45; 2008-2014), and only CTX isolates in subclade IIIb (n =
24; 2013). Temporal phylogenetic analysis estimated the divergence of these three
clades from the most recent common ancestor in approximately 1980. The CTX clade
IIIb was estimated to have evolved and diverged from the NY ancestor around 2004.
Furthermore, gradual temporal loss of genes encoding a D-alanine transporter,
involved in virulence, was observed. These genes were present in the isolates
endemic to NTX clade I and were gradually lost in clades II and III. The
virulence gene orgA, which is part of the Salmonella Pathogenicity Island 1, was
lost in a subgroup of Texas isolates in clades I and IIIb. All S. Cerro isolates
had an additional cytosine inserted in a cytosine-rich region of the virulence
gene sopA, resulting in premature termination of translation likely responsible
for loss of pathogenic capacity in humans. A group of closely related NY isolates
was characterized by the loss of hydrogen sulfide production due to the
truncation or complete loss of phsA. Our data suggest the ability of Salmonella
to rapidly diverge and adapt to specific niches (e.g., bovine niche), and to
modify virulence-related characteristics such as the ability to utilize
tetrathionate as an alternative electron acceptor, which is commonly used to
detect Salmonella. Overall, our results show that clinical outcome data and
genetic data for S. Cerro isolates, such as truncations in virulence genes
leading to novel pheno- and pathotypes, should be correlated to allow for
accurate risk assessment.
PMID- 28507538
TI - Candida lipolytica UCP0988 Biosurfactant: Potential as a Bioremediation Agent and
in Formulating a Commercial Related Product.
AB - The aim of the present study was to investigate the potential application of the
biosurfactant from Candida lipolytica grown in low-cost substrates, which has
previously been produced and characterized under optimized conditions as an
adjunct material to enhance the remediation processes of hydrophobic pollutants
and heavy metals generated by the oil industry and propose the formulation of a
safe and stable remediation agent. In tests carried out with seawater, the crude
biosurfactant demonstrated 80% oil spreading efficiency. The dispersion rate was
50% for the biosurfactant at a concentration twice that of the CMC. The
biosurfactant removed 70% of motor oil from contaminated cotton cloth in
detergency tests. The crude biosurfactant also removed 30-40% of Cu and Pb from
standard sand, while the isolated biosurfactant removed ~30% of the heavy metals.
The conductivity of solutions containing Cd and Pb was sharply reduced after
biosurfactants' addition. A product was prepared through adding 0.2% potassium
sorbate as preservative and tested over 120 days. The formulated biosurfactant
was analyzed for emulsification and surface tension under different pH values,
temperatures, and salt concentrations and tested for toxicity against the fish
Poecilia vivipara. The results showed that the formulation had no toxicity and
did not cause significant changes in the tensoactive capacity of the biomolecule
while maintaining activity demonstrating suitability for potential future
commercial product formulation.
PMID- 28507537
TI - Deep Sea Actinomycetes and Their Secondary Metabolites.
AB - Deep sea is a unique and extreme environment. It is a hot spot for hunting marine
actinomycetes resources and secondary metabolites. The novel deep sea
actinomycete species reported from 2006 to 2016 including 21 species under 13
genera with the maximum number from Microbacterium, followed by Dermacoccus,
Streptomyces and Verrucosispora, and one novel species for the other 9 genera.
Eight genera of actinomycetes were reported to produce secondary metabolites,
among which Streptomyces is the richest producer. Most of the compounds produced
by the deep sea actinomycetes presented antimicrobial and anti-cancer cell
activities. Gene clusters related to biosynthesis of desotamide, heronamide, and
lobophorin have been identified from the deep sea derived Streptomyces.
PMID- 28507539
TI - New Insight into Inter-kingdom Communication: Horizontal Transfer of Mobile Small
RNAs.
AB - Small RNAs (sRNAs), including small interfering RNAs (siRNAs) and microRNAs
(miRNAs), are conventionally regarded as critical molecular regulators of various
intracellular processes. However, recent accumulating evidence indicates that
sRNAs can be transferred within cells and tissues and even across species. In
plants, nematodes and microbes, these mobile sRNAs can mediate inter-kingdom
communication, environmental sensing, gene expression regulation, host-parasite
defense and many other biological functions. Strikingly, a recent study by our
group suggested that ingested plant miRNAs are transferred to blood, accumulate
in tissues and regulate transcripts in consuming animals. While our and other
independent groups' subsequent studies further explored the emerging field of
sRNA-mediated crosstalk between species, some groups reported negative results
and questioned its general applicability. Thus, further studies carefully
evaluating the horizontal transfer of exogenous sRNAs and its potential
biological functions are urgently required. Here, we review the current state of
knowledge in the field of the horizontal transfer of mobile sRNAs, suggest its
future directions and key points for examination and discuss its potential
mechanisms and application prospects in nutrition, agriculture and medicine.
PMID- 28507540
TI - Microbial Population Dynamics and Ecosystem Functions of Anoxic/Aerobic Granular
Sludge in Sequencing Batch Reactors Operated at Different Organic Loading Rates.
AB - The granular sludge process is an effective, low-footprint alternative to
conventional activated sludge wastewater treatment. The architecture of the
microbial granules allows the co-existence of different functional groups, e.g.,
nitrifying and denitrifying communities, which permits compact reactor design.
However, little is known about the factors influencing community assembly in
granular sludge, such as the effects of reactor operation strategies and influent
wastewater composition. Here, we analyze the development of the microbiomes in
parallel laboratory-scale anoxic/aerobic granular sludge reactors operated at low
(0.9 kg m-3d-1), moderate (1.9 kg m-3d-1) and high (3.7 kg m-3d-1) organic
loading rates (OLRs) and the same ammonium loading rate (0.2 kg NH4-N m-3d-1) for
84 days. Complete removal of organic carbon and ammonium was achieved in all
three reactors after start-up, while the nitrogen removal (denitrification)
efficiency increased with the OLR: 0% at low, 38% at moderate, and 66% at high
loading rate. The bacterial communities at different loading rates diverged
rapidly after start-up and showed less than 50% similarity after 6 days, and
below 40% similarity after 84 days. The three reactor microbiomes were dominated
by different genera (mainly Meganema, Thauera, Paracoccus, and Zoogloea), but
these genera have similar ecosystem functions of EPS production, denitrification
and polyhydroxyalkanoate (PHA) storage. Many less abundant but persistent taxa
were also detected within these functional groups. The bacterial communities were
functionally redundant irrespective of the loading rate applied. At steady-state
reactor operation, the identity of the core community members was rather stable,
but their relative abundances changed considerably over time. Furthermore,
nitrifying bacteria were low in relative abundance and diversity in all reactors,
despite their large contribution to nitrogen turnover. The results suggest that
the OLR has considerable impact on the composition of the granular sludge
communities, but also that the granule communities can be dynamic even at steady
state reactor operation due to high functional redundancy of several key guilds.
Knowledge about microbial diversity with specific functional guilds under
different operating conditions can be important for engineers to predict the
stability of reactor functions during the start-up and continued reactor
operation.
PMID- 28507541
TI - The Importance of Bacterial Culture to Food Microbiology in the Age of Genomics.
AB - Culture-based and genomics methods provide different insights into the nature and
behavior of bacteria. Maximizing the usefulness of both approaches requires
recognizing their limitations and employing them appropriately. Genomic analysis
excels at identifying bacteria and establishing the relatedness of isolates.
Culture-based methods remain necessary for detection and enumeration, to
determine viability, and to validate phenotype predictions made on the bias of
genomic analysis. The purpose of this short paper is to discuss the application
of culture-based analysis and genomics to the questions food microbiologists
routinely need to ask regarding bacteria to ensure the safety of food and its
economic production and distribution. To address these issues appropriate tools
are required for the detection and enumeration of specific bacterial populations
and the characterization of isolates for, identification, phylogenetics, and
phenotype prediction.
PMID- 28507543
TI - Long-term Monocyte Dysfunction after Sepsis in Humanized Mice Is Related to
Persisted Activation of Macrophage-Colony Stimulation Factor (M-CSF) and
Demethylation of PU.1, and It Can Be Reversed by Blocking M-CSF In Vitro or by
Transplanting Naive Autologous Stem Cells In Vivo.
AB - The duration of post-sepsis long-term immune suppression is poorly understood.
Here, we focused on the role of monocytes (MO) as the pivotal cells for long-term
regulation of post-sepsis milieu. Lost ability of MO to adapt is seen in several
acute conditions, but it is unclear for how long MO aberrancy post-sepsis can
persist. Interestingly, the positive feedback loop sustaining secretion of
macrophage-colony stimulation factor (M-CSF) can persist even after resolution of
sepsis and significantly alters performance of MO. Here, we investigated the
activation of M-CSF, and it as critical regulator of PU.1 in mice surviving 28
days after sepsis. Our primary readout was the ability of MO to differentiate
into dendritic cells (DCs; MO->iDC) in vitro since this is one of the critical
processes regulating a successful transition from innate to acquired immunity. We
utilized a survival modification of the cecal ligation and puncture (CLP) model
of sepsis in humanized mice. Animals were sacrificed 28 days after CLP
(tCLP+28d). Untouched (CONTR) or sham-operated (SHAM) animals served as controls.
Some animals received rescue from stem cells originally used for grafting 2 weeks
after CLP. We found profound decrease of MO->iDC in the humanized mice 28 days
after sepsis, demonstrated by depressed expression of CD1a, CD83, and CD209,
diminished production of IL-12p70, and depressed ability to stimulate T cells in
mice after CLP as compared to SHAM or CONTR. In vitro defect in MO->iDC was
accompanied by in vivo decrease of BDCA-3+ endogenous circulating DC.
Interestingly, post-CLP MO had persistent activation of M-CSF pathway, shown by
exaggerated secretion of M-CSF, activation of PU.1, and demethylation of SPII.
Neutralization of the M-CSF in vitro reversed the post-CLP MO->iDC aberration.
Furthermore, transplantation of naive, autologous stem cell-derived MO restored
CLP-deteriorated ability of MO to become DC, measured as recovery of CD1a
expression, enhanced production of IL-12p70, and ability of IL-4 and GM-CSF MO to
stimulate allogeneic T cells. Our results suggest the role of epigenetic mediated
M-CSF aberration in mediating post-sepsis immune system recovery.
PMID- 28507542
TI - Reactive Oxygen Species-Mediated Cellular Stress Response and Lipid Accumulation
in Oleaginous Microorganisms: The State of the Art and Future Perspectives.
AB - Microbial oils, which are mainly extracted from yeasts, molds, and algae, have
been of considerable interest as food additives and biofuel resources due to
their high lipid content. While these oleaginous microorganisms generally produce
only small amounts of lipids under optimal growth conditions, their lipid
accumulation machinery can be induced by environmental stresses, such as nutrient
limitation and an inhospitable physical environmental. As common second
messengers of many stress factors, reactive oxygen species (ROS) may act as a
regulator of cellular responses to extracellular environmental signaling.
Furthermore, increasing evidence indicates that ROS may act as a mediator of
lipid accumulation, which is associated with dramatic changes in the
transcriptome, proteome, and metabolome. However, the specific mechanisms of ROS
involvement in the crosstalk between extracellular stress signaling and
intracellular lipid synthesis require further investigation. Here, we summarize
current knowledge on stress-induced lipid biosynthesis and the putative role of
ROS in the control of lipid accumulation in oleaginous microorganisms.
Understanding such links may provide guidance for the development of stress-based
strategies to enhance microbial lipid production.
PMID- 28507544
TI - Within-Epitope Interactions Can Bias CTL Escape Estimation in Early HIV
Infection.
AB - As human immunodeficiency virus (HIV) begins to replicate within hosts, immune
responses are elicited against it. Escape mutations in viral epitopes-immunogenic
peptide parts presented on the surface of infected cells-allow HIV to partially
evade these responses, and thus rapidly go to fixation. The faster they go to
fixation, i.e., the higher their escape rate, the larger the selective pressure
exerted by the immune system is assumed to be. This relation underpins the
rationale for using escapes to assess the strength of immune responses. However,
escape rate estimates are often obtained by employing an aggregation procedure,
where several mutations that affect the same epitope are aggregated into a
single, composite epitope mutation. The aggregation procedure thus rests upon the
assumption that all within-epitope mutations have indistinguishable effects on
immune recognition. In this study, we investigate how violation of this
assumption affects escape rate estimates. To this end, we extend a previously
developed simulation model of HIV that accounts for mutation, selection, and
recombination to include different distributions of fitness effects (DFEs) and
inter-mutational genomic distances. We use this discrete time Wright-Fisher based
model to simulate early within-host evolution of HIV for DFEs and apply standard
estimation methods to infer the escape rates. We then compare true with estimated
escape rate values. We also compare escape rate values obtained by applying the
aggregation procedure with values estimated without use of that procedure. We
find that across the DFEs analyzed, the aggregation procedure alters the
detectability of escape mutations: large-effect mutations are overrepresented
while small-effect mutations are concealed. The effect of the aggregation
procedure is similar to extracting the largest-effect mutation appearing within
an epitope. Furthermore, the more pronounced the over-exponential decay of the
DFEs, the more severely true escape rates are underestimated. We conclude that
the aggregation procedure has two main consequences. On the one hand, it leads to
a misrepresentation of the DFE of fixed mutations. On the other hand, it conceals
within-epitope interactions that may generate irregularities in mutation
frequency trajectories that are thus left unexplained.
PMID- 28507545
TI - Clinical and Molecular Heterogeneity of RTEL1 Deficiency.
AB - Typical features of dyskeratosis congenita (DC) resulting from excessive telomere
shortening include bone marrow failure (BMF), mucosal fragility, and pulmonary or
liver fibrosis. In more severe cases, immune deficiency and recurring infections
can add to disease severity. RTEL1 deficiency has recently been described as a
major genetic etiology, but the molecular basis and clinical consequences of
RTEL1-associated DC are incompletely characterized. We report our observations in
a cohort of six patients: five with novel biallelic RTEL1 mutations p.Trp456Cys,
p.Ile425Thr, p.Cys1244ProfsX17, p.Pro884_Gln885ins53X13, and one with novel
heterozygous mutation p.Val796AlafsX4. The most unifying features were
hypocellular BMF in 6/6 and B-/NK-cell lymphopenia in 5/6 patients. In addition,
three patients with homozygous mutations p.Trp456Cys or p.Ile425Thr also suffered
from immunodeficiency, cerebellar hypoplasia, and enteropathy, consistent with
Hoyeraal-Hreidarsson syndrome. Chromosomal breakage resembling a homologous
recombination defect was detected in patient-derived fibroblasts but not in
hematopoietic compartment. Notably, in both cellular compartments, differential
expression of 1243aa and 1219/1300aa RTEL1 isoforms was observed. In fibroblasts,
response to ionizing irradiation and non-homologous end joining were not
impaired. Telomeric circles did not accumulate in patient-derived primary cells
and lymphoblastoid cell lines, implying alternative pathomechanisms for telomeric
loss. Overall, RTEL1-deficient cells exhibited a phenotype of replicative
exhaustion, spontaneous apoptosis and senescence. Specifically, CD34+ cells
failed to expand in vitro, B-cell development was compromised, and T-cells did
not proliferate in long-term culture. Finally, we report on the natural history
and outcome of our patients. While two patients died from infections,
hematopoietic stem cell transplantation (HSCT) resulted in sustained engraftment
in two patients. Whether chemotherapy negatively impacts on the course and onset
of other DC-related symptoms remains open at present. Early-onset lung disease
occurred in one of our patients after HSCT. In conclusion, RTEL deficiency can
show a heterogeneous clinical picture ranging from mild hypocellular BMF with
B/NK cell lymphopenia to early-onset, very severe, and rapidly progressing
cellular deficiency.
PMID- 28507546
TI - Extracellular Signal-Regulated Kinase Signaling in CD4-Expressing Cells Inhibits
Osteochondromas.
AB - Defects in cartilage homeostasis can give rise to various skeletal disorders
including osteochondromas. Osteochondromas are benign bone tumors caused by
excess accumulation of chondrocytes, the main cell type of cartilage. The
extracellular signal-regulated kinase (ERK) pathway is a major signaling node
that functions within chondrocytes to regulate their growth and differentiation.
However, it is not known whether the ERK pathway in other cell types regulates
cartilage homeostasis. We show here that mice with a germline deficiency of Erk1
and a conditional deletion of Erk2 in cells that express CD4, or expressed CD4 at
one point in development, unexpectedly developed bone deformities. The bone
lesions were due to neoplastic outgrowths of chondrocytes and disordered growth
plates, similar to tumors observed in the human disease, osteochondromatosis.
Chondrocyte accumulation was not due to deletion of Erk2 in the T cells. Rather,
CD4cre was expressed in cell types other than T cells, including a small fraction
of chondrocytes. Surprisingly, the removal of T cells accelerated osteochondroma
formation and enhanced disease severity. These data show for the first time that
T cells impact the growth of osteochondromas and describe a novel model to study
cartilage homeostasis and osteochondroma formation.
PMID- 28507547
TI - Deletion of Dock10 in B Cells Results in Normal Development but a Mild Deficiency
upon In Vivo and In Vitro Stimulations.
AB - We sought to identify genes necessary to induce cytoskeletal change in B cells.
Using gene expression microarray, we compared B cells stimulated with interleukin
4 (IL-4) and anti-CD40 antibodies that induce B cell spreading, cell motility,
tight aggregates, and extensive microvilli with B cells stimulated with
lipopolysaccharide that lack these cytoskeletal changes. We identified 84 genes
with 10-fold or greater expression in anti-CD40 + IL-4 stimulated B cells, one of
these encoded the guanine nucleotide exchange factor (GEF) dedicator of
cytokinesis 10 (Dock10). IL-4 selectively induced Dock10 expression in B cells.
Using lacZ expression to monitor Dock10 promoter activity, we found that Dock10
was expressed at all stages during B cell development. However, specific deletion
of Dock10 in B cells was associated with a mild phenotype with normal B cell
development and normal B cell spreading, polarization, motility, chemotaxis,
aggregation, and Ig class switching. Dock10-deficient B cells showed lower
proliferation in response to anti-CD40 and IL-4 stimulation. Moreover, the IgG
response to soluble antigen in vivo was lower when Dock10 was specifically
deleted in B cells. Together, we found that most B cell responses were intact in
the absence of Dock10. However, specific deletion of Dock10 in B cells was
associated with a mild reduction in B cell activation in vitro and in vivo.
PMID- 28507548
TI - Iron- and Hepcidin-Independent Downregulation of the Iron Exporter Ferroportin in
Macrophages during Salmonella Infection.
AB - Retention of iron in tissue macrophages via upregulation of hepcidin (HAMP) and
downregulation of the iron exporter ferroportin (FPN) is thought to participate
in the establishment of anemia of inflammation after infection. However, an
upregulation of FPN has been proposed to limit macrophages iron access to
intracellular pathogens. Therefore, we studied the iron homeostasis and in
particular the regulation of FPN after infection with Salmonella enterica serovar
Typhimurium in mice presenting tissue macrophages with high iron (AcB61), basal
iron (A/J and wild-type mice), or low iron (Hamp knock out, Hamp-/-) levels. The
presence of iron in AcB61 macrophages due to extravascular hemolysis and strong
erythrophagocytosis activity favored the proliferation of Salmonella in the
spleen and liver with a concomitant decrease of FPN protein expression. Despite
systemic iron overload, no or slight increase in Salmonella burden was observed
in Hamp-/- mice compared to controls. Importantly, FPN expression at both mRNA
and protein levels was strongly decreased during Salmonella infection in Hamp-/-
mice. The repression of Fpn mRNA was also observed in Salmonella-infected
cultured macrophages. In addition, the downregulation of FPN was associated with
decreased iron stores in both the liver and spleen in infected mice. Our findings
show that during Salmonella infection, FPN is repressed through an iron and
hepcidin-independent mechanism. Such regulation likely provides the cellular iron
indispensable for the growth of Salmonella inside the macrophages.
PMID- 28507550
TI - Editorial: Parasites in the Tropic-A New Paradigm Shift.
PMID- 28507551
TI - Deciphering Genomic Regions for High Grain Iron and Zinc Content Using
Association Mapping in Pearl Millet.
AB - Micronutrient malnutrition, especially deficiency of two mineral elements, iron
[Fe] and zinc [Zn] in the developing world needs urgent attention. Pearl millet
is one of the best crops with many nutritional properties and is accessible to
the poor. We report findings of the first attempt to mine favorable alleles for
grain iron and zinc content through association mapping in pearl millet. An
association mapping panel of 130 diverse lines was evaluated at Delhi, Jodhpur
and Dharwad, representing all the three pearl millet growing agro-climatic zones
of India, during 2014 and 2015. Wide range of variation was observed for grain
iron (32.3-111.9 ppm) and zinc (26.6-73.7 ppm) content. Genotyping with 114
representative polymorphic SSRs revealed 0.35 mean gene diversity. STRUCTURE
analysis revealed presence of three sub-populations which was further supported
by Neighbor-Joining method of clustering and principal coordinate analysis
(PCoA). Marker-trait associations (MTAs) were analyzed with 267 markers (250 SSRs
and 17 genic markers) in both general linear model (GLM) and mixed linear model
(MLM), however, MTAs resulting from MLM were considered for more robustness of
the associations. After appropriate Bonferroni correction, Xpsmp 2261 (13.34% R2
value), Xipes 0180 (R2-value of 11.40%) and Xipes 0096 (R2-value of 11.38%) were
consistently associated with grain iron and zinc content for all the three
locations. Favorable alleles and promising lines were identified for across and
specific environments. PPMI 1102 had highest number (7) of favorable alleles,
followed by four each for PPMFeZMP 199 and PPMI 708 for across the environment
performance for both grain Fe and Zn content, while PPMI 1104 had alleles
specific to Dharwad for grain Fe and Zn content. When compared with the reference
genome Tift 23D2B1-P1-P5, Xpsmp 2261 amplicon was identified in intergenic region
on pseudomolecule 5, while the other marker, Xipes 0810 was observed to be
overlapping with aspartic proteinase (Asp) gene on pseudomolecule 3. Thus, this
study can help in breeding new lines with enhanced micronutrient content using
marker-assisted selection (MAS) in pearl millet leading to improved well-being
especially for women and children.
PMID- 28507552
TI - Genome-Wide Identification and Expression Analysis of the Biotin Carboxyl Carrier
Subunits of Heteromeric Acetyl-CoA Carboxylase in Gossypium.
AB - Acetyl-CoA carboxylase is an important enzyme, which catalyzes acetyl-CoA's
carboxylation to produce malonyl-CoA and to serve as a committed step for de novo
fatty acid biosynthesis in plastids. In this study, 24 putative cotton BCCP genes
were identified based on the lately published genome data in Gossypium. Among
them, 4, 4, 8, and 8 BCCP homologs were identified in Gossypium raimondii, G.
arboreum, G. hirsutum, and G. barbadense, respectively. These genes were divided
into two classes based on a phylogenetic analysis. In each class, these homologs
were relatively conserved in gene structure and motifs. The chromosomal
distribution pattern revealed that all the BCCP genes were distributed equally on
corresponding chromosomes or scaffold in the four cotton species. Segmental
duplication was a predominant duplication event in both of G. hirsutum and G.
barbadense. The analysis of the expression profile showed that 8 GhBCCP genes
expressed in all the tested tissues with changed expression levels, and GhBCCP
genes belonging to class II were predominantly expressed in developing ovules.
Meanwhile, the expression analysis for the 16 cotton BCCP genes from G.
raimondii, G. arboreum and G. hirsutum showed that they were induced or
suppressed by cold or salt stress, and their expression patterns varied among
different tissues. These findings will help to determine the functional and
evolutionary characteristics of the BCCP genes in Gossypium species.
PMID- 28507549
TI - Human Lung Mononuclear Phagocytes in Health and Disease.
AB - The lungs are vulnerable to attack by respiratory insults such as toxins,
allergens, and pathogens, given their continuous exposure to the air we breathe.
Our immune system has evolved to provide protection against an array of potential
threats without causing collateral damage to the lung tissue. In order to swiftly
detect invading pathogens, monocytes, macrophages, and dendritic cells (DCs)
together termed mononuclear phagocytes (MNPs)-line the respiratory tract with the
key task of surveying the lung microenvironment in order to discriminate between
harmless and harmful antigens and initiate immune responses when necessary. Each
cell type excels at specific tasks: monocytes produce large amounts of cytokines,
macrophages are highly phagocytic, whereas DCs excel at activating naive T cells.
Extensive studies in murine models have established a division of labor between
the different populations of MNPs at steady state and during infection or
inflammation. However, a translation of important findings in mice is only
beginning to be explored in humans, given the challenge of working with rare
cells in inaccessible human tissues. Important progress has been made in recent
years on the phenotype and function of human lung MNPs. In addition to a
substantial population of alveolar macrophages, three subsets of DCs have been
identified in the human airways at steady state. More recently, monocyte-derived
cells have also been described in healthy human lungs. Depending on the source of
samples, such as lung tissue resections or bronchoalveolar lavage, the specific
subsets of MNPs recovered may differ. This review provides an update on existing
studies investigating human respiratory MNP populations during health and
disease. Often, inflammatory MNPs are found to accumulate in the lungs of
patients with pulmonary conditions. In respiratory infections or inflammatory
diseases, this may contribute to disease severity, but in cancer patients this
may improve clinical outcomes. By expanding on this knowledge, specific lung MNPs
may be targeted or modulated in order to attain favorable responses that can
improve preventive or treatment strategies against respiratory infections, lung
cancer, or lung inflammatory diseases.
PMID- 28507555
TI - Moderate Drought Stress Affected Root Growth and Grain Yield in Old, Modern and
Newly Released Cultivars of Winter Wheat.
AB - To determine root growth and grain yield of winter wheat (Triticum aestivum L)
under moderate drought stress, a nursery experiment and a field trial were
conducted with or without water stress using three representative cultivars
released in different years: CW134 (old landrace), CH58 (modern cultivar) and CH1
(new release). In the nursery experiment, plants were grown in soil-filled
rhizoboxes under moderate drought (MD, 55% of field capacity) or well-watered
(WW, 85% of field capacity) conditions. In the field trial, plots were either
rainfed (moderate drought stress) or irrigated with 30 mm of water at each of
stem elongation, booting and anthesis stages (irrigated). Compared to drought
stress, grain yields increased under sufficient water supply in all cultivars,
particular the newly released cultivar CH1 with 70% increase in the nursery and
23% in the field. When well-watered (nursery) or irrigated (field), CH1 had the
highest grain yields compared to the other two cultivars, but produced similar
yield to the modern cultivar (CH58) under water-stressed (nursery) or rainfed
(field) conditions. When exposed to drought stress, CW134 had the highest topsoil
root dry mass in topsoil but lowest in subsoil among the cultivars at stem
elongation, anthesis, and maturity, respectively; while CH1 had the lowest
topsoil and highest subsoil root dry mass at respective sampling times. Topsoil
root mass and root length density were negatively correlated with grain yield for
the two water treatments in nursery experiment. When water was limited, subsoil
root mass was positively correlated with thousand kernel weight (TKW). In the
field trial, CH1 and CH58 used less water during vegetative growth than CW134,
but after anthesis stage, CH1 used more water than the other two cultivars,
especially in the soil profile below 100 cm, which was associated with the
increased TKW. This study demonstrated that greater root mass and root length
density in subsoil layers, with enhanced access to subsoil water after anthesis,
contribute to high grain yield when soil water is scarce.
PMID- 28507553
TI - Virus-Bacteria Rice Co-Infection in Africa: Field Estimation, Reciprocal Effects,
Molecular Mechanisms, and Evolutionary Implications.
AB - Simultaneous infection of a single plant by various pathogen species is
increasingly recognized as an important modulator of host resistance and a driver
of pathogen evolution. Because plants in agro-ecosystems are the target of a
multitude of pathogenic microbes, co-infection could be frequent, and
consequently important to consider. This is particularly true for rapidly
intensifying crops, such as rice in Africa. This study investigated potential
interactions between pathogens causing two of the major rice diseases in Africa:
the Rice yellow mottle virus (RYMV) and the bacterium Xanthomonas oryzae pathovar
oryzicola (Xoc) in order to: 1/ document virus-bacteria co-infection in rice in
the field, 2/ explore experimentally their consequences in terms of symptom
development and pathogen multiplication, 3/ test the hypothesis of underlying
molecular mechanisms of interactions and 4/ explore potential evolutionary
consequences. Field surveys in Burkina Faso revealed that a significant
proportion of rice fields were simultaneously affected by the two diseases. Co
infection leads to an increase in bacterial specific symptoms, while a decrease
in viral load is observed compared to the mono-infected mock. The lack of effect
found when using a bacterial mutant for an effector specifically inducing
expression of a small RNA regulatory protein, HEN1, as well as a viral genotype
specific effect, both suggest a role for gene silencing mechanisms mediating the
within-plant interaction between RYMV and Xoc. Potential implications for
pathogen evolution could not be inferred because genotype-specific effects were
found only for pathogens originating from different countries, and consequently
not meeting in the agrosystem. We argue that pathogen-pathogen-host interactions
certainly deserve more attention, both from a theoretical and applied point of
view.
PMID- 28507556
TI - Differential Effects of Phosphatidylinositol 4-Kinase (PI4K) and 3-Kinase (PI3K)
Inhibitors on Stomatal Responses to Environmental Signals.
AB - Specific cellular components including products of phosphatidylinositol (PI)
metabolism play an important role as signaling molecules in stomatal responses to
environmental signals. In this study, pharmacological inhibitors of a set of
cellular components, including PI4-kinase (PI4K) and PI3K, were used to
investigate stomatal closure in response to CO2, darkness, and abscisic acid
(ABA). Treatment with PAO, a specific inhibitor of PI4K, specifically inhibited
the stomatal response to CO2 compared with that to darkness and ABA. In contrast,
treatment with LY294002, a PI3K-specific inhibitor, specifically inhibited the
stomatal response to darkness compared with that to CO2 and ABA. The specific
inhibitory effects of PAO and LY294002 were also observed as changes in the
spatial density of dot-like structures labeled by green fluorescent protein
tagged PATROL1, a protein that controls stomatal aperture possibly via regulation
of H+-ATPase amount in guard cell plasma membranes. Our results suggest an
important role for PI4K and PI3K in the CO2 and darkness signal transduction
pathways, respectively, that mediate PATROL1 dynamics.
PMID- 28507554
TI - Large Differences in Gene Expression Responses to Drought and Heat Stress between
Elite Barley Cultivar Scarlett and a Spanish Landrace.
AB - Drought causes important losses in crop production every season. Improvement for
drought tolerance could take advantage of the diversity held in germplasm
collections, much of which has not been incorporated yet into modern breeding.
Spanish landraces constitute a promising resource for barley breeding, as they
were widely grown until last century and still show good yielding ability under
stress. Here, we study the transcriptome expression landscape in two genotypes,
an outstanding Spanish landrace-derived inbred line (SBCC073) and a modern
cultivar (Scarlett). Gene expression of adult plants after prolonged stresses,
either drought or drought combined with heat, was monitored. Transcriptome of
mature leaves presented little changes under severe drought, whereas abundant
gene expression changes were observed under combined mild drought and heat.
Developing inflorescences of SBCC073 exhibited mostly unaltered gene expression,
whereas numerous changes were found in the same tissues for Scarlett. Genotypic
differences in physiological traits and gene expression patterns confirmed the
different behavior of landrace SBCC073 and cultivar Scarlett under abiotic
stress, suggesting that they responded to stress following different strategies.
A comparison with related studies in barley, addressing gene expression responses
to drought, revealed common biological processes, but moderate agreement
regarding individual differentially expressed transcripts. Special emphasis was
put in the search of co-expressed genes and underlying common regulatory motifs.
Overall, 11 transcription factors were identified, and one of them matched cis
regulatory motifs discovered upstream of co-expressed genes involved in those
responses.
PMID- 28507557
TI - Exogenous Glutathione Enhances Mercury Tolerance by Inhibiting Mercury Entry into
Plant Cells.
AB - Despite the increasing understanding of the crucial roles of glutathione (GSH) in
cellular defense against heavy metal stress as well as oxidative stress, little
is known about the functional role of exogenous GSH in mercury (Hg) tolerance in
plants. Here, we provide compelling evidence that GSH contributes to Hg tolerance
in diverse plants. Exogenous GSH did not mitigate the toxicity of cadmium (Cd),
copper (Cu), or zinc (Zn), whereas application of exogenous GSH significantly
promoted Hg tolerance during seed germination and seedling growth of Arabidopsis
thaliana, tobacco, and pepper. By contrast, addition of buthionine sulfoximine,
an inhibitor of GSH biosynthesis, severely retarded seed germination and seedling
growth of the plants in the presence of Hg. The effect of exogenous GSH on Hg
specific tolerance was also evident in the presence of other heavy metals, such
as Cd, Cu, and Zn, together with Hg. GSH treatment significantly decreased H2O2
and O2- levels and lipid peroxidation, but increased chlorophyll content in the
presence of Hg. Importantly, GSH treatment resulted in significantly less
accumulation of Hg in Arabidopsis plants, and thin layer chromatography and
nuclear magnetic resonance analysis revealed that GSH had much stronger binding
affinity to Hg than to Cd, Cu, or Zn, suggesting that tight binding of GSH to Hg
impedes Hg uptake, leading to low Hg accumulation in plant cells. Collectively,
the present findings reveal that GSH is a potent molecule capable of conferring
Hg tolerance by inhibiting Hg accumulation in plants.
PMID- 28507558
TI - ZmDof30 Negatively Regulates the Promoter Activity of the Pollen-Specific Gene
Zm908.
AB - The maize (Zea mays) pollen-predominant gene Zm908, a novel small-peptide gene,
was reported to play critical roles in pollen germination and pollen tube growth
in our previous work. In this study, we aimed to explore the regulatory mechanism
of Zm908. The putative promoter of Zm908 was cloned and analyzed. The activity
analysis of a series of promoter truncations in different tissues of transgenic
tobacco plants indicated that the Zm908 promoter is pollen-specific and that the
126 to -68 region is crucial for pollen expression. The 5' deletion analysis of
the -126 to -68 region revealed that the -126 to -102 region functions as a
transcriptional suppression element. ZmDof30, which is predominantly expressed in
pollen and whole anthers, was cloned and characterized. ZmDof30-GFP localized to
the nuclei of maize protoplasts and possessed no transcriptional activation
activity in a yeast system. ZmDof30 could bind to the AAAG elements in p184
sequence containing the -126 to +58 region of the Zm908 promoter in vitro and in
vivo, and negatively regulated p184 activity in tobacco leaves. Collectively,
ZmDof30 may function as a Zm908 transcriptional repressor in pollen, and these
results may provide a better understanding of the regulation of the Zm908 gene.
Additionally, the pollen-specific Zm908 promoter may be valuable for genetically
engineering male sterility.
PMID- 28507559
TI - The DnaJ Gene Family in Pepper (Capsicum annuum L.): Comprehensive
Identification, Characterization and Expression Profiles.
AB - The DnaJ proteins which function as molecular chaperone played critical roles in
plant growth and development and response to heat stress (HS) and also called
heat shock protein 40 based on molecular weight. However, little was reported on
this gene family in pepper. Recently, the release of the whole pepper genome
provided an opportunity for identifying putative DnaJ homologous. In this study,
a total of 76 putative pepper DnaJ genes (CaDnaJ01 to CaDnaJ76) were identified
using bioinformatics methods and classified into five groups by the presence of
the complete three domains (J-domain, zinc finger domain, and C-terminal domain).
Chromosome mapping suggested that segmental duplication and tandem duplication
were occurred in evolution. The multiple stress-related cis-elements were found
in the promoter region of these CaDnaJ genes, which indicated that the CaDnaJs
might be involved in the process of responding to complex stress conditions. In
addition, expression profiles based on RNA-seq showed that the 47 CaDnaJs were
expressed in at least one tissue tested. The result implied that they could be
involved in the process of pepper growth and development. qRT-PCR analysis found
that 80.60% (54/67) CaDnaJs were induced by HS, indicated that they could
participated in pepper response to high temperature treatments. In conclusion,
all these results would provide a comprehensive basis for further analyzing the
function of CaDnaJ members and be also significant for elucidating the
evolutionary relationship in pepper.
PMID- 28507560
TI - Corrigendum: Co-expression with the Type 3 Secretion Chaperone CesT from
Enterohemorrhagic E. coli Increases Accumulation of Recombinant Tir in Plant
Chloroplasts.
AB - [This corrects the article on p. 283 in vol. 8, PMID: 28321227.].
PMID- 28507562
TI - Antivenomics as a tool to improve the neutralizing capacity of the crotalic
antivenom: a study with crotamine.
AB - BACKGROUND: Snakebite treatment requires administration of an appropriate
antivenom that should contain antibodies capable of neutralizing the venom. To
achieve this goal, antivenom production must start from a suitable immunization
protocol and proper venom mixtures. In Brazil, antivenom against South American
rattlesnake (Crotalus durissus terrificus) bites is produced by public
institutions based on the guidelines defined by the regulatory agency of the
Brazilian Ministry of Health, ANVISA. However, each institution uses its own
mixture of rattlesnake venom antigens. Previous works have shown that crotamine,
a toxin found in Crolatus durissus venom, shows marked individual and
populational variation. In addition, serum produced from crotamine-negative
venoms fails to recognize this molecule. METHODS: In this work, we used an
antivenomics approach to assess the cross-reactivity of crotalic antivenom
manufactured by IVB towards crotamine-negative venom and a mixture of crotamine
negative/crotamine-positive venoms. RESULTS: We show that the venom mixture
containing 20% crotamine and 57% crotoxin produced a strong immunogenic response
in horses. Antivenom raised against this venom mixture reacted with most venom
components including crotamine and crotoxin, in contrast to the antivenom raised
against crotamine-negative venom. CONCLUSIONS: These results indicate that
venomic databases and antivenomics analysis provide a useful approach for
choosing the better venom mixture for antibody production and for the subsequent
screening of antivenom cross-reactivity with relevant snake venom components.
PMID- 28507561
TI - Deletion Extents Are Not the Cause of Clinical Variability in 22q11.2 Deletion
Syndrome: Does the Interaction between DGCR8 and miRNA-CNVs Play a Major Role?
AB - In humans, the most common genomic disorder is the hemizygous deletion of the
chromosome 22q11.2 region, that results in the "22q11.2 deletion syndrome"
(22q11.2DS). A peculiarity of 22q11.2DS is its great phenotypic variability that
makes this pathology a classic example of a syndrome with variable expressivity
and incomplete penetrance. The reasons for this variability have not been
elucidated yet, and the molecular substrates underlying the different clinical
features of 22q11.2DS are still debated. A cohort of 21 patients has been
analyzed by array CGH in order to detect some of the genetic differences that may
influence this variability. Two aspects have been investigated: (1) the precise
localization of the deletion breakpoints within the low copy repeats (LCRs), (2)
the additional Copy Number Variations (CNVs) elsewhere in the genome, by
analyzing their gene content. Both protein-coding genes and miRNAs were
considered, in order to discover possible epistatic interactions between genes of
the 22q11.2 region and the rest of the genome. Eighteen out of twenty-one
patients had a deletion of ~3 Mb mediated by LCR22-A and D, whereas 3/21 had a
smaller deletion. The breakpoints within the LCR22-A and D do not have a major
role in the phenotypic variability since they are rather clustered and the small
differences concern genes that are not directly related to clinical signs of
22q11.2DS. A detailed analysis of the gene content of 22q11.2 deleted region
indicates that this syndrome could be a bioenergetic disorder or consequence of
an altered post-transcriptional gene regulation, due to the presence of DGCR8, a
major player of the microRNA (miRNA) biogenesis. Only four genes with
mitochondrial function are harbored in the additional CNVs, whereas 11 miRNA, all
related to biological pathways present in the 22q11.2DS, have been detected in
19/21 patients. CNVs and miRNAs are new entities that have changed the order of
complexity at the level of gene expression and regulation, thus CNV-miRNAs (miRNA
harbored in the CNVs) are potential functional variants that should be considered
high priority candidate variants in genotype-phenotype association studies.
Deletion of DGCR8, the main actor in miRNA biogenesis, amplifies this
variability. To our knowledge, this is the first report that focus on the miRNA
CNVs in 22q11.2DS, with the aim of trying to better understand their role in the
variable expressivity and incomplete penetrance.
PMID- 28507563
TI - Can coffee consumption lower the risk of Alzheimer's disease and Parkinson's
disease? A literature review.
AB - In light of the fact that the number of elderly citizens in society is steadily
increasing, the search for dietary factors which might prolong mental agility is
growing in significance. Coffee, together with its main ingredient, caffeine, has
been the focus of much attention from various researchers, as data on its
beneficial effects on human health continue to accumulate. Most reports indicate
that moderate coffee consumption may in fact lower the risk for common
neurodegenerative conditions, i.e. Alzheimer's and Parkinson's diseases.
Regardless, due to their complex pathogenesis as well as methodology of
scientific research, the exact impact of coffee consumption remains to be fully
elucidated. At present, it seems safe to inform the general public that coffee
drinkers need not fear for their health. Possibly, in the future experts will
recommend drinking coffee not only to satisfy individual taste preferences but
also to decrease age-related mental deterioration.
PMID- 28507565
TI - Laparoscopic and open liver resection - a literature review with meta-analysis.
AB - INTRODUCTION: In recent years laparoscopic approach to liver resections has
gained important attention from surgeons worldwide. The aim of this review was to
compare the results of laparoscopic and open liver resections. MATERIAL AND
METHODS: We have performed a search in Medline, Embase and the Cochrane Library
databases. Studies comparing laparoscopic and open liver resections were
included. RESULTS: No randomized clinical trial were identified. In the 16
observational studies included in the analysis there were 927 laparoscopic and
1049 open liver resections. The laparoscopy group had lower blood loss (MD =
244.93 ml, p < 0.00001), lower odds of transfusion (OR = 0.35, p = 0.0002), lower
odds of positive margins on pathology report (OR = 0.22, p < 0.00001), lower odds
of readmission (OR = 0.36, p = 0.04), lower odds of pulmonary (OR = 0.38, p =
0.003) and cardiac complications (OR = 0.30, p = 0.02) and lower odds of
postoperative liver failure (OR = 0.24, p = 0.001), but in many cases the results
were based on a low number of events reported in included studies. CONCLUSIONS:
Laparoscopic resection of liver yields complications rates comparable to open
resection, but the results are based on low quality evidence from nonrandomised
studies.
PMID- 28507566
TI - Comparison of intra-articular versus intravenous application of tranexamic acid
in total knee arthroplasty: a meta-analysis of randomized controlled trials.
AB - INTRODUCTION: There is much controversy about the optimal application of
tranexamic acid (TXA) in total knee arthroplasty (TKA). The purpose of this meta
analysis was to compare the efficacy of the intra-articular and intravenous
regimens of TXA in TKA. MATERIAL AND METHODS: A literature search of the PubMed,
Embase and Cochrane Library databases was performed. Randomized controlled trials
comparing the result of intra-articular and intravenous application of TXA during
TKA were included. The focus was on the outcomes of blood loss, transfusion
requirement and thromboembolic complications. RESULTS: Six studies were eligible
for data extraction and meta-analysis. We found no statistically significant
difference between intra-articular and intravenous administration of tranexamic
acid in terms of total blood loss (WMD, 6.01; 95% CI: -96.78 to 108.79; p =
0.91), drain output (WMD = -20.26; 95% CI: -51.34 to 10.82; p = 0.20), hemoglobin
drop (WMD = 0.33; 95% CI: -0.31 to 0.98; p = 0.31), or the incidences of
transfusion (RR = 0.98; 95% CI: 0.56-1.70; p = 0.93) as well as deep vein
thrombosis (RR = 0.49; 95% CI: 0.09-2.73; p = 0.42). CONCLUSIONS: In comparison
with intravenous application of TXA, intra-articular application had a comparable
effect on reducing blood loss and the transfusion rate without increasing the
complication rate.
PMID- 28507564
TI - Management of the hormonal syndrome of neuroendocrine tumors.
AB - Gastroenteropancreatic neuroendocrine tumors (GEP/NET) are unusual and rare
neoplasms that present many clinical challenges. They characteristically
synthesize store and secrete a variety of peptides and neuroamines which can lead
to the development of distinct clinical syndrome, however many are clinically
silent until late presentation with mass effects. Management strategies include
surgery cure and cytoreduction with the use of somatostatin analogues.
Somatostatin have a broad range of biological actions that include inhibition of
exocrine and endocrine secretions, gut motility, cell proliferation, cell
survival and angiogenesis. Five somatostatin receptors (SSTR1-SSTR5) have been
cloned and characterized. Somatostatin analogues include octreotide and
lanreotide are effective medical tools in the treatment and present selectivity
for SSTR2 and SSTR5. During treatment is seen disapperance of flushing,
normalization of bowel movements and reduction of serotonin and 5-hydroxyindole
acetic acid (5-HIAA) secretion. Telotristat represents a novel approach by
specifically inhibiting serotonin synthesis and as such, is a promising potential
new treatment for patients with carcinoid syndrome. To pancreatic functionig
neuroendocrine tumors belongs insulinoma, gastrinoma, glucagonoma and VIP-oma.
Medical management in patients with insulinoma include diazoxide which suppresses
insulin release. Also mTOR inhibitors may inhibit insulin secretion. Treatment of
gastrinoma include both proton pump inhibitors (PPIs) and histamine H2 - receptor
antagonists. In patients with glucagonomas hyperglycaemia can be controlled using
insulin and oral blood glucose lowering drugs. In malignant glucagonomas
smatostatin analogues are effective in controlling necrolytic migratory
erythemia. Severe cases of the VIP-oma syndrome require supplementation of fluid
losses. Octreotide reduce tumoral VIP secretion and control secretory diarrhoea.
PMID- 28507567
TI - Performance of pfHRP2 versus pLDH antigen rapid diagnostic tests for the
detection of Plasmodium falciparum: a systematic review and meta-analysis.
AB - INTRODUCTION: There have been many inconsistent reports about the performance of
histidine-rich protein 2 (HRP2) and lactate dehydrogenase (LDH) antigens as rapid
diagnostic tests (RDTs) for the diagnosis of past Plasmodium falciparum
infections. This meta-analysis was performed to determine the performance of
pfHRP2 versus pLDH antigen RDTs in the detection of P. falciparum. MATERIAL AND
METHODS: After a systematic review of related studies, Meta-DiSc 1.4 software was
used to calculate the pooled sensitivity, specificity, positive likelihood ratio
(PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Forest
plots and summary receiver operating characteristic curve (SROC) analysis were
used to summarize the overall test performance. RESULTS: Fourteen studies which
met the inclusion criteria were included in the meta-analysis. The summary
performances for pfHRP2- and pLDH-based tests in the diagnosis of P. falciparum
infections were as follows: pooled sensitivity, 96.3% (95.8-96.7%) vs. 82.6%
(81.7-83.5%); specificity, 86.1% (85.3-86.8%) vs. 95.9% (95.4-96.3%); diagnostic
odds ratio (DOR), 243.31 (97.679-606.08) vs. 230.59 (114.98-462.42); and area
under ROCs, 0.9822 versus 0.9849 (all p < 0.001). CONCLUSIONS: The two RDTs
performed satisfactorily for the diagnosis of P. falciparum, but the pLDH tests
had higher specificity, whereas the pfHRP2 tests had better sensitivity. The
pfHRP2 tests had slightly greater accuracy compared to the pLDH tests. A
combination of both antigens might be a more reliable approach for the diagnosis
of malaria.
PMID- 28507568
TI - Effect of ramipril/hydrochlorothiazide and ramipril/canrenone combination on
atrial fibrillation recurrence in hypertensive type 2 diabetic patients with and
without cardiac autonomic neuropathy.
AB - INTRODUCTION: The aim of this study was to compare the effect of
ramipril/canrenone versus ramipril/hydrochlorothiazide (HCTZ) combination on
atrial fibrillation (AF) recurrence in type 2 diabetic hypertensives with and
without cardiac autonomic neuropathy (CAN). MATERIAL AND METHODS: A total of 289
hypertensive type 2 diabetic patients, 95 with CAN, in sinus rhythm but with at
least two episodes of AF in the previous 6 months were randomized to ramipril 5
mg plus canrenone 50 mg (titrated to 10/100 mg) or to ramipril 5 mg plus HCTZ
12.5 mg (titrated to 10/25 mg) or to amlodipine 5 mg (titrated to 10 mg) for 1
year. Clinic blood pressure (BP) and a 24-h ECG were evaluated monthly. Patients
were asked to report any episode of symptomatic AF and to perform an ECG as early
as possible. Serum procollagen type I carboxy-terminal peptide (PIP) and carboxy
terminal telopeptide of collagen type I (CITP) were evaluated before and after
each treatment period. RESULTS: Blood pressure was similarly and significantly
reduced by all treatments. A total of 51% of patients with amlodipine had a
recurrence of AF, as did 31% of patients with ramipril/HCTZ (p < 0.05 vs.
amlodipine) and 13% of patients with ramipril/canrenone (p < 0.01 vs. amlodipine
and p < 0.05 vs. ramipril/HCTZ). A similar trend was found in diabetic patients
with CAN. Both combinations reduced PIP and increased CITP, but the effects of
ramipril/canrenone were significantly more marked. CONCLUSIONS: These findings
suggest that in type 2 diabetic hypertensives, ramipril/canrenone treatment was
more effective than ramipril/HCTZ in reducing AF recurrence. This could be
related to the greater improvement in cardiac fibrosis.
PMID- 28507569
TI - Effects of a novel ascorbate-based protocol on infarct size and ventricle
function in acute myocardial infarction patients undergoing percutaneous coronary
angioplasty.
AB - INTRODUCTION: This study was designed to test the hypothesis that high-dose
ascorbate prior to reperfusion followed by low chronic oral doses ameliorate
myocardial reperfusion injury (MRI) in acute myocardial infarction patients
subjected to primary percutaneous coronary angioplasty (PCA). MATERIAL AND
METHODS: A randomized double-blind placebo-controlled and multicenter clinical
trial was performed on acute myocardial infarction (AMI) patients who underwent
PCA. Sodium ascorbate (320 mmol/l, n = 53) or placebo (n = 46) was infused 30 min
prior to PCA. Blood samples were drawn at enrolment (M1), after balloon deflation
(M2), 6-8 h after M2 (M3) and at discharge (M4). Total antioxidant capacity of
plasma (ferric reducing ability of plasma - FRAP), erythrocyte reduced
glutathione (GSH) and plasma ascorbate levels were determined in blood samples.
Cardiac magnetic resonance (CMR) was performed at 7-15 days and 2-3 months
following PCA. Ninety-nine patients were enrolled. In 67 patients, the first CMR
was performed, and 40 patients completed follow-up. RESULTS: The ascorbate group
showed significantly higher ascorbate and FRAP levels and a decrease in the GSH
levels at M2 and M3 (p < 0.05). There were no significant differences in the
infarct size, indexed end-systolic volume and ejection fraction at both CMRs.
There was a significant amelioration in the decreased ejection fraction between
the first and second CMR in the ascorbate group (p < 0.05). CONCLUSIONS:
Ascorbate given prior to reperfusion did not show a significant difference in
infarct size or ejection fraction. However, it improved the change in ejection
fraction determined between 7-15 days and 2-3 months. This result hints at a
possible functional effect of ascorbate to ameliorate MRI.
PMID- 28507570
TI - ScaI atrial natriuretic peptide gene polymorphisms and their possible association
with postoperative atrial fibrillation - a preliminary report.
AB - INTRODUCTION: Atrial fibrillation (AF) is a frequently encountered complication
after coronary artery bypass grafting (CABG), but its underlying mechanisms are
still unclear. The natriuretic peptides have been reported as markers for
predicting the occurrence of postoperative AF. This study evaluates whether the
ScaI ANP gene polymorphisms predict the occurrence of postoperative AF. MATERIAL
AND METHODS: A prospective study of 203 consecutive patients with coronary artery
disease undergoing elective CABG was undertaken for atrial natriuretic peptide
(ANP) ScaI gene polymorphism. Several perioperative data were analysed.
Postoperative AF was defined as lasting for at least 15 min, confirmed by 12-lead
ECG and occurring within 6 postoperative days. The ScaI polymorphism of the ANP
gene was determined by polymerase chain reaction (PCR). Size-dependent separation
of the PCR products on a polyacrylamide gel was followed by staining with
ethidium bromide. RESULTS: The total frequency of AF was 19.7%. The frequencies
of ScaI ANP gene polymorphisms were as follows: A1A1 4.90%, A1A2 59.60% and A2A2
35.46%. In order to assess the hypothesis that the A2 allele is a marker of
increased risk of postoperative atrial fibrillation, the odds ratio (OR) was
calculated: A2 vs. non-A2, OR = 0.98 (0.23-4.1), p = 0.97, which was not
significant. The odds ratios for A2A2 and A1A1 were not significant either: A2A2
vs. non-A2A2, OR = 1.11 (0.54-2.29), p = 0.76, and A1A1 vs. non-A1A1, OR = 1.17
(0.23-5.92), p = 0.84. CONCLUSIONS: ANP genotype did not predispose to the
incidence of "new-onset" AF.
PMID- 28507572
TI - Transient dilutional acidosis but no lactic acidosis upon cardiopulmonary bypass
in patients undergoing coronary artery bypass grafting.
AB - INTRODUCTION: Dilutional acidosis may result from the introduction of a large
fluid volume into the patients' systemic circulation, resulting in a considerable
dilution of endogenous bicarbonate in the presence of a constant carbon dioxide
partial pressure. Its significance or even existence, however, has been strongly
questioned. Blood gas samples of patients operated on with standard
cardiopulmonary bypass (CPB) were analyzed in order to provide further evidence
for the existence of dilutional acidosis. MATERIAL AND METHODS: Between 07/2014
and 10/2014, a total of 25 consecutive patients scheduled for elective isolated
coronary artery bypass grafting with CPB were enrolled in this prospective
observational study. Blood gas samples taken regularly after CPB initiation were
analyzed for dilutional effects and acid-base changes. RESULTS: After CPB
initiation, hemoglobin concentration dropped from an average initial value of
12.8 g/dl to 8.8 g/dl. Before the beginning of CPB, the mean value of the
patients' pH and base excess (BE) value averaged 7.41 and 0.5 mEq/l,
respectively. After the onset of CPB, pH and BE values significantly dropped to a
mean value of 7.33 (p < 0.0001) and -3.3 mEq/l (p < 0.0001), respectively, within
the first 20 min. In the following period during CPB they recovered to 7.38 and
0.5 mEq/l, respectively, on average. Patients did not show overt lactic acidosis.
CONCLUSIONS: The present data underline the general existence of dilutional
acidosis, albeit very limited in its duration. In patients undergoing coronary
artery bypass grafting it seems to be the only obvious disturbance in acid-base
homeostasis during CPB.
PMID- 28507571
TI - Transcatheter paravalvular leak closure and hemolysis - a prospective registry.
AB - INTRODUCTION: Paravalvular leak (PVL) related to a surgical prosthetic valve may
be associated with clinically significant hemolysis. The influence of
transcatheter PVL closure (TPVLC) on hemolysis remains uncertain. MATERIAL AND
METHODS: The prospective registry included patients undergoing TPVLC due to PVL
related heart failure and/or hemolysis. Procedural data, laboratory markers of
hemolysis and heart failure status were recorded at baseline, discharge and at 1-
and 6-month follow-up. RESULTS: Of 116 patients from all those qualified for
TPVLC, 79 fulfilled the inclusion/exclusion criteria. Hemolysis was significantly
more frequent in patients with mitral location of PVL and with calcifications in
its channel. After TPVLC prompt reduction of lactate dehydrogenase activity
(617.0 (342.0-899.0) vs. 397 (310.0-480.5) IU/l, p < 0.05) and gradual resolution
of anemia (hemoglobin (HGB) 11.7 (10.4-13.8) vs. 13.4 (12.9-13.8) g%, p < 0.05)
over 6 months were noted. Effective closure of PVL (> 90% reduction of PVL cross
sectional area) resulted in a more prominent increase of red blood cell count and
HGB than in patients with residual regurgitation. The TPVLC-related exacerbation
of hemolysis was recorded in 14 patients. Its risk was aggravated by presence of
significant hemolysis at baseline or residual flow either by a partially
uncovered channel or across the occluder. Reduction of hemolysis after successful
TPVLC was sustained in 6-month follow-up. CONCLUSIONS: Risk factors for PVL
related hemolysis were the presence of calcifications in the defect and mitral
location of PVL. The TPVLC effectively reduced hemolysis if at least 90%
reduction of PVL cross sectional area was achieved. The effect was sustained in 6
month follow-up. Incomplete closure of PVL may increase the magnitude of
hemolysis after TPVLC, but it occurred rarely.
PMID- 28507573
TI - Admission D-dimer testing for differentiating acute aortic dissection from other
causes of acute chest pain.
AB - INTRODUCTION: The present study aims to evaluate the utility of D-dimer testing
for differentiating the causes of acute chest pain, including acute aortic
dissection (AAD), pulmonary embolism (PE), acute myocardial infarction (AMI),
unstable angina (UA), and other uncertain diagnoses of chest pain. MATERIAL AND
METHODS: Consecutive patients admitted for acute chest pain within 24 h from
symptom onset were enrolled prospectively, and plasma D-dimer levels were
measured on admission. Diagnoses of AAD, PE, AMI, and UA were confirmed by
standard methods. RESULTS: A total of 790 patients were enrolled, including 202
AAD, 43 PE, 315 AMI, 136 UA, and 94 cases of other uncertain diagnoses. D-dimer
levels were significantly higher in patients with AAD and PE than in those with
AMI, UA, and other uncertain diagnoses (p < 0.001), but they were comparable
between patients with AAD and PE (p = 0.065). Moreover, patients with type A AAD
had higher D-dimer levels than those with type B AAD (p = 0.022). Receiver
operating characteristic (ROC) curve analysis showed that a D-dimer level < 0.5
ug/ml was a good predictor for ruling out AAD, with a sensitivity of 94.0% and a
specificity of 56.8%. At a cut-off level of 0.5 ug/ml, the negative and positive
likelihood ratios were 0.10 and 2.18, respectively, with a positive predictive
value of 42.6% and a negative predictive value of 96.6%. CONCLUSIONS: The D-dimer
level within 24 h after symptom onset might be helpful for differentiating AAD
from other causes of chest pain.
PMID- 28507574
TI - Blood groups and acute aortic dissection type III.
AB - INTRODUCTION: Acute aortic type III dissection is one of the most catastrophic
events, with in-hospital mortality ranging between 10% and 12%. The majority of
patients are treated medically, but complicated dissections, which represent 15%
to 20% of cases, require surgical or thoracic endovascular aortic repair (TEVAR).
For the best outcomes adequate blood transfusion support is required. Interest in
the relationship between blood type and vascular disease has been established.
The aim of our study is to evaluate distribution of blood groups among patients
with acute aortic type III dissection and to identify any kind of relationship
between blood type and patient's survival. MATERIAL AND METHODS: From January
2005 to December 2014, 115 patients with acute aortic type III dissection were
enrolled at the Clinic of Vascular and Endovascular Surgery in Belgrade, Serbia
and retrospectively analyzed. Patients were separated into two groups. The
examination group consisted of patients with a lethal outcome, and the control
group consisted of patients who survived. RESULTS: The analysis of the blood
groups and RhD typing between groups did not reveal a statistically significant
difference (p = 0.220). CONCLUSIONS: Our results indicated no difference between
different blood groups and RhD typing with respect to in-hospital mortality of
patients with acute aortic dissection type III.
PMID- 28507576
TI - Red blood cell distribution width in patients with limb, chest and head trauma.
AB - INTRODUCTION: This study investigated the values of red blood cell distribution
width (RDW), an emerging and independent predictor of morbidity and mortality, in
patients with limb, chest and head trauma. MATERIAL AND METHODS: The study sample
consisted of all patients who attended the emergency department (ED) of the
University Hospital of Parma for limb, chest and head traumas requiring admission
to hospital wards during the year 2014. The controls consisted of outpatients
living in the same geographical area and undergoing routine laboratory testing
for health check-up. RESULTS: The final study sample consisted of 290 patients
with limb (n = 97), chest (n = 49) or head (n = 144) trauma and 967 outpatients.
Significantly increased RDW values at admission were observed in all trauma
patients compared with controls. Although the frequency of increased RDW (>
14.6%) was higher in all trauma patients than in controls, a subanalysis revealed
that increased RDW values were significantly more frequent in patients with head
trauma than in controls, but not in those with limb or chest trauma. In
multivariate analysis, a significant association was found between head trauma
and hemoglobin (p < 0.001) or RDW (p = 0.005). Head trauma patients had a ~3-fold
higher likelihood of increased RDW values than controls. The negative and
positive predictive values of increased RDW for predicting the presence of head
trauma were 0.90 (95% CI: 0.88-0.92) and 0.24 (95% CI: 0.19-0.30). CONCLUSIONS:
The results of this study highlight that RDW is increased in patients admitted to
the ED with head trauma.
PMID- 28507575
TI - Association between telomere length and complete blood count in US adults.
AB - INTRODUCTION: Telomere length (TL) is related to age-related health outcomes, but
little is known about the relationship between TL and complete blood count (CBC)
parameters. We aimed to determine the relationship between TL and CBC in a sample
of healthy US adults. MATERIAL AND METHODS: Participants in the National Health
and Nutrition Examination Survey (NHANES) recruited between 1999 and 2002 who had
essential data on total CBC and TL were studied. We computed age- and race
adjusted mean values for total CBC using analysis of covariance (ANCOVA). All
statistical analyses accounted for the survey design and sample weights by using
SPSS Complex Samples v22.0 (IBM Corp, Armonk, NY). RESULTS: Of the 8892 eligible
participants, 47.8% (n = 4123) were men. The mean age was 41.8 years overall,
41.0 years in men and 42.6 in women (p = 0.238). The sex-stratified ANCOVA showed
no significant difference in the total CBC across TL quartiles (all p > 0.05) in
both sexes. In the adjusted model, there was a significant negative relationship
with monocyte count (beta = -0.051, 95% CI: -0.422; -0.142), mean cell hemoglobin
(beta = -0.051, 95% CI: -0.038; -0.011) and red cell distribution width (beta =
0.031, 95% CI: -0.054; -0.003), while there was a significant positive
relationship with basophil ratio (beta = 0.046, 95% CI: 0.049-0.171).
CONCLUSIONS: These results support the possibility that telomere attrition may be
a marker for reduced proliferative reserve in hematopoietic progenitor cells.
PMID- 28507577
TI - Peritoneal lavage examination as a prognostic tool in cases of gastric cancer.
AB - INTRODUCTION: Peritoneal tumor seeding is a common form of recurrence after
gastric cancer surgery. The finding of free tumor cells and/or elevation of tumor
markers in the peritoneal fluid could predict intraperitoneal tumor recurrence.
The results of these examination can be used for indication of aggressive
treatment modalities such as hyperthermic intraperitoneal chemotherapy (HIPEC).
MATERIAL AND METHODS: We have operated on 105 patients suffering from gastric
cancer. The control group consisted of 12 patients without malignant disease.
Peritoneal lavage fluid or ascites was collected immediately after laparotomy and
examined by cytology and biochemistry (levels of carcinoembryonic antigen (CEA)
and Ca 19-9). Sensitivity, specificity, stage correlation and overall survival
were observed. RESULTS: Elevation of tumor markers or the finding of free
intraperitoneal tumor cells predicts recurrence. The prognosis of these patients
is same as in stage IV TNM classification with median survival time less than 1
year (p = 0.713). Patients with negative cytology have median survival time 5
years contrary to them with positive cytology (p < 0.001). Sensitivity of the
cytology was 34% and specificity was 85%. Sensitivity of biochemistry was 53%
(combination of both markers) and specificity was 100%. CONCLUSIONS: This study
confirms the importance of peritoneal fluid examination for the prognosis. We
cannot recommend routine use as an indicator for HIPEC due to low sensitivity,
but the result of cytological examination is an independent factor for patient
survival.
PMID- 28507578
TI - Lobular carcinoma in situ of the breast - correlation between minimally invasive
biopsy and final pathology.
AB - INTRODUCTION: Lobular carcinoma in situ (LCIS) is regarded as a non-obligate
precursor of invasive breast cancer (IBC). Hence, the optimal management of LCIS
found on minimally invasive breast biopsy remains a subject of debate. The aim of
this study was to evaluate the correlation of biopsy findings with postoperative
histology and to identify risk factors for upstaging to IBC. MATERIAL AND
METHODS: Twenty-seven patients with pure LCIS diagnosed on image-guided biopsy
(vacuum-assisted or core-needle) underwent subsequent surgery. Clinical,
radiological and histological features were compared to the final pathology after
surgical excision. RESULTS: Median age of patients was 56 years while median size
of LCIS was 15 mm. Final examination demonstrated IBC foci in 29.6% of lesions.
Upstaged patients were younger and had larger lesions but without statistical
significance (p = 0.07 and p = 0.09, respectively). Palpable tumours (p =
0.0004), BIRADS 5 lesions (p = 0.0001), masses (p = 0.016) and pleomorphic LCIS
(p = 0.0001) had a significantly increased rate of upstaging. Guidance of the
procedure (ultrasound vs. stereotactic) was significantly associated with the
upstaging risk (p = 0.016), while the importance of the biopsy technique (core
needle vs. vacuum-assisted) was not confirmed (p = 0.37). After excluding
pleomorphic LCIS and mass-forming classic LCIS, there was no risk of upstaging
for lesions with BIRADS 4 mammographic abnormalities. CONCLUSIONS: Pleomorphic
histology, mass formation and BIRADS 5 category reflect more aggressive behaviour
of LCIS and identify patients who need subsequent surgery. For other patients,
close follow-up could be a safe alternative.
PMID- 28507579
TI - Assessment of concentrations of sTRAIL ligand and its receptors sTRAIL-R1 and
sTRAIL-R2 - markers monitoring the course of the extrinsic pathway of apoptosis
induction: potential application in ovarian cancer diagnostics.
AB - INTRODUCTION: TNF-related apoptosis-inducing ligand (TRAIL) together with its
receptors are involved in activation of the extrinsic pathway of apoptosis. Due
to the special role of the apoptosis pathway in pathogenesis of ovarian cancers,
the aim of the study was to assess concentrations of sTRAIL, sTRAIL-R1 and sTRAIL
R2 in serum of affected women. MATERIAL AND METHODS: The study group included 85
women with diagnosed ovarian tumors: 35 women with ovarian serous cystadenoma, 15
women with ovarian teratoma and 35 women with serous cystadenocarcinoma. The
control group consisted of 30 healthy women. Concentrations of studied parameters
were measured by ELISA methods. RESULTS: Serum levels of all studied parameters
were higher in serum of women with ovarian tumors than in the controls, but their
concentrations varied depending on the clinical diagnosis. The highest
concentration of TRAIL was found in serum of women with ovarian cancer, the
highest sTRAIL-R1 level in serum of women with ovarian mature teratoma, and the
highest sTRAIL-R2 level in serum of women with ovarian serous cystadenoma.
CONCLUSIONS: The state of immunosuppression accompanying neoplastic disease
depends on the extrinsic pathway of apoptosis induction in the TRAIL/TRAIL-R
system. Determination of TRAIL-R1 and TRAIL-R2 levels may prove to be useful in
ovarian tumor differential diagnostics, which requires further research.
PMID- 28507580
TI - Impact of antenatal oxytocin infusion on neonatal respiratory morbidity
associated with elective cesarean section.
AB - INTRODUCTION: This study was designed to estimate respiratory morbidity
associated with elective cesarean section (ECS) and to determine the effect of
antenatal oxytocin exposure on this morbidity. MATERIAL AND METHODS: Nine hundred
and sixty-five neonates >= 37 weeks' gestation delivered by cesarean section
during 1 year were included in this retrospective study and classified into two
groups according to oxytocin exposure before cesarean deliveries. Respiratory
morbidity for each group was recorded and statistically analyzed. RESULTS:
Transient tachypnea of newborn (TTN) was significantly more frequent in group II
(ECS group) than in group I (cesarean section after oxytocin exposure) (8.19% vs.
2.92%; respectively, p = 0.0006). Mechanical ventilation, continuous positive
airway pressure (CPAP) and oxygen therapy were significantly more frequent in
group II than in group I (1.78%, 2.14% and 4.28% versus 0.44%, 0.58% and 1.46%,
respectively; p = 0.039, and p = 0.033 and p = 0.009, respectively). The number
of newborns admitted to the neonatal unit and neonatal intensive care unit (NICU)
was significantly higher in group II than in group I (6.41% and 2.14% vs. 2.05%
and 0.58%, respectively; p = 0.001 and p = 0.033, respectively). Surfactant,
fluid therapies and parenteral nutrition were significantly more frequent in
group II than in group I (2.14%, 4.28% and 2.49% vs. 0.15%, 1.46% and 0.73%,
respectively; p = 0.001, p = 0.009 and p = 0.02, respectively). CONCLUSIONS:
Neonatal respiratory morbidity associated with ECS significantly decreased after
antenatal oxytocin exposure. A significant reduction of neonatal respiratory
morbidity would be achieved if ECS were performed after 39 weeks' gestation.
PMID- 28507581
TI - Long-term outcomes in children with chronic kidney disease stage 5 over the last
40 years.
AB - INTRODUCTION: We evaluated outcomes in children with chronic kidney disease stage
5 (CKD 5) treated in the first pediatric dialysis unit in Poland during 1973
2012. MATERIAL AND METHODS: The retrospective analysis included 208 children with
CKD 5 undergoing renal replacement therapy (RRT), stratified into four decades of
treatment: 1973-1982, 1983-1992, 1993-2002, and 2003-2012. RESULTS: The most
common causes of CKD 5 included glomerulonephritis in 27.4% and pyelonephritis
secondary to urinary tract anomalies in 25.5% of children. Among 208 children,
172 (82.7%) survived and 17.3% died. Kidney transplantation (KTx) was performed
in 47.6% of children, including pre-emptive KTx in 1.92% of children. Chronic
dialysis was continued in 34.1% of children, and RRT was withdrawn in 1%. The
overall mortality rate was 6.2 per 100 patient-years, and 3-year survival was
83.9%. The highest mortality rate of 23.4 per 100 patient-years was observed
among children in whom RRT was initiated in 1973-1982, with subsequent reduction
of the mortality rate to 4.5 and 2.1 per 100 patient-years in 1993-2002 and 1983
1992 respectively. No deaths were noted after 2002. Cardiovascular problems were
the most common cause of death, found in 36.1% of patients (p < 0.01). Identified
risk factors for mortality included young age, low residual diuresis, anemia at
the time of RRT initiation, and hypertriglyceridemia and hypoalbuminemia during
RRT. CONCLUSIONS: In years 1973-2012 significant improvement in prognosis among
children with CKD 5 was achieved. Identified predictors of mortality included
young age at initiation of RRT, low residual diuresis, anemia and
hypertriglyceridemia.
PMID- 28507582
TI - Decreased activity of butyrylcholinesterase in blood plasma of patients with
chronic obstructive pulmonary disease.
AB - INTRODUCTION: Butyrylcholinesterase (BChE) is involved in the metabolism of
endogenous lipids and xenobiotics, such as esters of carboxylic or phosphoric
acids. Butyrylcholinesterase activity is associated with both inflammation and
oxidative stress. Changes in the activity of this enzyme have been observed in
various diseases such as liver cirrhosis, diabetes, neurodegenerative disease and
others. MATERIAL AND METHODS: The study involved 30 patients with chronic
obstructive pulmonary disease (COPD) and 18 healthy subjects. The COPD patients
were divided according to the severity of the disease by applying the
classification of COPD based on GOLD standards for forced expiratory volume in 1
s (FEV1) and the FEV1/forced expiratory volume (FVC) ratio. The control group
comprised blood samples collected from healthy subjects without concomitant
diseases related to the respiratory system. Butyrylcholinesterase activity, lipid
peroxidation and total antioxidant capacity (TAC) were determined in the blood
plasma. RESULTS: A significant (p < 0.05) decrease in the activity of BChE,
associated with an increase in lipid peroxidation and a decrease in the total
antioxidant capacity, was observed in blood plasma of patients with chronic
obstructive pulmonary disease. CONCLUSIONS: The study shows for the first time
that activity of BChE in the blood plasma of patients diagnosed with chronic
obstructive pulmonary disease is considerably reduced compared with healthy
subjects. These changes were accompanied by a decrease of TAC and an increase of
lipid peroxidation, which suggests that they may be related to the oxidative
stress induced by COPD disease.
PMID- 28507583
TI - Intravenous drug use - an independent predictor for HCV genotypes 3 and 4
infection among HIV/HCV co-infected patients.
AB - INTRODUCTION: About one quarter of human immunodeficiency virus (HIV) infected
persons in Serbia have also been found to be hepatitis C virus (HCV) co-infected.
In the general population, HCV genotype 1 has been shown to be the most prevalent
one. Here, we present the first study on the distribution of HCV genotypes among
HIV/HCV co-infected patients in Serbia, in relation to epidemiological and
clinical features. MATERIAL AND METHODS: The study included HIV/HCV co-infected
and a group of HCV mono-infected patients in the period 1998-2012, with
collection of epidemiological, clinical, and behavioral data using a standardized
questionnaire. The HCV genotyping to the level of pure genotype was performed by
reverse hybridization. RESULTS: Intravenous drug use (IDU) was found to be
significantly more prevalent among the co-infected patients (p < 0.01). HCV
genotype 1 was detected in 87% of patients with mono-infection, compared to 46.3%
of patients with co-infection (p < 0.01); genotypes 3 and 4 were significantly
more common among co-infected patients (6% and 5%, vs. 27% and 25%,
respectively). Multivariate logistic regression confirmed IDU, infection with non
1 HCV genotype and HCV viral load over 5 log to be predictors of HIV co
infection. CONCLUSIONS: The HCV genotypes 3 and 4 were found to be significantly
more prevalent among HIV/HCV co-infected patients in Serbia, compared to HCV mono
infected patients, but also more prevalent compared to the European HIV/HCV co
infected cohort. History of IDU represents an independent predictor of HCV
genotypes 3 and 4 infection, with important implications for treatment.
PMID- 28507584
TI - Effects of adenosine receptor antagonists in MPTP mouse model of Parkinson's
disease: mitochondrial DNA integrity.
AB - INTRODUCTION: In Parkinson's disease (PD), compelling data indicate a functional
link between adenosine/dopamine receptors and the progression of the
neurodegenerative process. The present study was carried out to evaluate the
effect of the non-selective adenosine receptor (ADR) antagonist caffeine, as well
as the selective antagonists 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an
ADRsA1 antagonist, and ((E)-1,3-diethyl-8-(3,4-dimethoxystyryl)-7-methyl-3,7
dihydro-1H-purine-2,6-dione) (KW-6002), an ADRsA2A antagonist, on the prevention
of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism in
mice. MATERIAL AND METHODS: Mice were allocated to five groups: group I - control
group; group II: MPTP group, received four injections of MPTP (20 mg/kg, i.p.) at
2 h intervals; groups III, IV, V: received MPTP and i.p. caffeine (20 mg/kg/day)
or DPCPX (5 mg/kg/day) or KW-6002 (10 mg/kg/day) starting one week before MPTP
injection and continuing for 2 weeks. RESULTS: Therapy with caffeine or KW-6002
not only led to the reversibility of movement dysfunction and increased the
concentrations of dopamine and ATP levels (p < 0.05), but also, ameliorates the
dopaminergic neuron loss and restored the mtDNA and nDNA integrity (p < 0.05).
Furthermore, in passive avoidance test, caffeine and DPCPX significantly (p <
0.05) reversed the MPTP-induced memory deficits, whereas the specific ADRsA2A
antagonist did not. CONCLUSIONS: The current results provide evidence that
blockade of both ADRsA1 and ADRsA2A has therapeutic implications in alleviating
MPTP-induced motor and cognitive dysfunction and might be a promising candidate
for treatment of PD.
PMID- 28507587
TI - An unusual etiology of torsade de pointes-induced syncope.
PMID- 28507585
TI - CTGF upregulation correlates with MMP-9 level in airway remodeling in a murine
model of asthma.
AB - INTRODUCTION: Connective tissue growth factor (CTGF) mediates hypertrophy,
proliferation, and extracellular matrix synthesis. Matrix metalloproteinase (MMP)
plays a role in airway extracellular matrix remodeling. The correlation between
CTGF and MMP in airway remodeling of asthma was unknown. This study investigated
lung CTGF expression and its correlation with MMP and airway structural changes
in a murine model of asthma. MATERIAL AND METHODS: Female BALB/c mice were
sensitized and challenged by intraperitoneal injections and intranasal phosphate
buffered saline (PBS) or ovalbumin (OVA). Airway responsiveness and serum OVA
specific IgE were measured. Airway structural changes were quantified by
morphometric analysis. Differential cell counts and MMP-2, MMP-9, and tissue
inhibitor of metalloproteinase (TIMP)-1 were evaluated in bronchoalveolar lavage
fluid (BALF). Lung CTGF was determined by Western blot. RESULTS: Serum OVA
specific IgE level and airway responsiveness in enhanced pause (Penh) is
significantly higher in sensitized mice challenged with OVA compared to PBS
challenged mice. MMP-2, MMP-9, and TIMP-1 in BALF were significantly higher in
OVA mice. Airway structural changes of animals' lungs with OVA challenge showed
increased thickness of the smooth muscle layer and numbers of Goblet cells and
inflammatory cells and eosinophils near airways and perivascular areas. Lung CTGF
expression significantly increased in OVA-challenged mice. CTGF expressions
positively correlated with MMP-9 (r = 0.677, p < 0.05), TIMP-1 (r = 0.574, p <
0.05) and thickness of the smooth muscle layer (r = 0.499, p < 0.05).
CONCLUSIONS: This study indicates that CTGF upregulation correlates with MMP-9,
probably involved in the pathogenesis of airway remodeling of asthma.
PMID- 28507588
TI - Henoch-Schonlein purpura in a pediatric patient with lupus.
PMID- 28507589
TI - Successful treatment of a 20-year nonhealing venous leg ulcer in a patient with
systemic lupus erythematosus.
PMID- 28507586
TI - Neutrophil elastase stimulates MUC5AC expression in human biliary epithelial
cells: a possible pathway of PKC/Nox/ROS.
AB - INTRODUCTION: Bacterial infection and bile flow retardation form a vicious cycle
which promotes stone formation and recurrence, and it seems that mucin
overexpression plays an important role in this process. However, the mechanism of
increased mucus secretion in the biliary tract by bacterial infection and its
treatment remain unclear. MATERIAL AND METHODS: Human biliary epithelial cells
were induced by neutrophil elastase (NE), and H2O2 production in the cell
supernatants was detected by a specific kit, and then cells were pretreated with
a H2O2 inhibitor, and expression of MUC5AC was detected by real-time polymerase
chain reaction (PCR), Western blot, and immunohistochemistry. Moreover, selective
PKC and Nox inhibitors, apocynin and bisindolylmaleimide I, were used to pretreat
cells and detect H2O2, MUC5AC mRNA and protein expression. Then, we pretreated
cells with selective inhibitors or NE, and detected transforming growth factor
alpha (TGF-alpha) using an ELISA kit. RESULTS: H2O2 production increased in an NE
dose-dependent manner (p < 0.001), and NE upregulated MUC5AC expression at both
mRNA and protein levels, while DMTU, could reduce this high expression (p < 0.01
at mRNA level, p < 0.001 at grey analysis for western blot and p < 0.01 at mean
density for immunohistochemical staining at protein level). Moreover, apocynin
and bisindolylmaleimide I could reduce the H2O2 production stimulated by NE (p <
0.05), and reduce MUC5AC high expression (p < 0.01 at mRNA level, p < 0.001 at
both grey analysis for western blot and mean density for immunohistochemical
staining at protein level). In addition, NE induced TGF-alpha production, and any
of the three selective inhibitors could reduce it (p < 0.05). CONCLUSIONS: NE
induced reactive oxygen species participated in the upregulation of MUC5AC
production. Moreover, protein kinase C and NADPH oxidase (Nox) regulate MUC5AC
production in NE-challenged human biliary epithelial cells.
PMID- 28507590
TI - Epithelioid hemangioendothelioma presenting as fever of unknown origin.
PMID- 28507592
TI - Incarcerated recurrent inguinal hernia containing an acute appendicitis (Amyand
hernia): an extremely rare surgical situation.
PMID- 28507591
TI - Marginal zone B-cell lymphoma mimicking extramedullary plasmacytoma and the
clinical outcome after treatment.
PMID- 28507593
TI - Short Questionnaire for Workplace Analysis (KFZA): factorial validation in
physicians and nurses working in hospital settings.
AB - BACKGROUND: In recent years, there has been an increasing interest in
psychosocial workplace risk assessments in Germany. One of the questionnaires
commonly employed for this purpose is the Short Questionnaire for Workplace
Analysis (KFZA). Originally, the KFZA was developed and validated for office
workers. The aim of the present study was to examine the factorial validity of
the KFZA when applied to hospital settings. Therefore, we examined the factorial
structure of a questionnaire that contained all the original items plus an
extension adding 11 questions specific to hospital workplaces and analyzed both,
the original version and the extended version. METHODS: We analyzed questionnaire
data of a total of 1731 physicians and nurses obtained over a 10-year period.
Listwise exclusion of data sets was applied to account for variations in
questionnaire versions and yielded 1163 questionnaires (1095 for the extended
version) remaining for factor analysis. To examine the factor structure, we
conducted a principal component factor analysis. The number of factors was
determined using the Kaiser criterion and scree-plot methods. Factor
interpretation was based on orthogonal Varimax rotation as well as oblique
rotation. RESULTS: The Kaiser criterion revealed a 7-factor solution for the 26
items of the KFZA, accounting for 62.0% of variance. The seven factors were
named: "Social Relationships", "Job Control", "Opportunities for Participation
and Professional Development", "Quantitative Work Demands", "Workplace
Environment", "Variability" and "Qualitative Work Demands". The factor analysis
of the 37 items of the extended version yielded a 9-factor solution. The two
additional factors were named "Consequences of Strain" and "Emotional Demands".
Cronbach's alpha ranged from 0.63 to 0.87 for these scales. CONCLUSIONS: Overall,
the KFZA turned out to be applicable to hospital workers, and its content-related
structure was replicated well with some limitations. However, instead of the 11
factors originally proposed for office workers, a 7-factor solution appeared to
be more suitable when employed in hospitals. In particular, the items of the KFZA
factor "Completeness of Task" might need adaptation for the use in hospitals. Our
study contributes to the assessment of the validity of this popular instrument
and should stimulate further psychometric testing.
PMID- 28507594
TI - Pain threshold reflects psychological traits in patients with chronic pain: a
cross-sectional study.
AB - BACKGROUND: Chronic pain enhances sensory sensitivity and induces the biased
development of psychological traits such as depression and pain catastrophizing,
leading to the formation of heterogeneous conditions. Fluctuations in the sensory
related thresholds of non-injured sites (with normal peripheral tissue) in
patients with chronic pain are thought to be related to central sensitization.
The objectives of this study were to analyze the association between pain
tolerance thresholds (PTTs) in non-injured sites and the psychological traits of
patients with chronic pain and to evaluate the usefulness of PTT measures in
assessments of pathological conditions related to chronic pain. METHODS: This
study included 57 patients with chronic pain. The PTTs were measured in non
injured sites with quantitative sensory testing (QST) with electrical stimulation
and then classified with cluster analysis. The Short-Form McGill Pain
Questionnaire was used to subjectively assess pain in the injured sites. The
Minnesota Multiphasic Personality Inventory (MMPI) was used to assess the
patients' psychological traits. RESULTS: Based on the cluster analysis of PTTs,
the patients were classified into a High-Sensitivity group and an Others group
consisting of the remaining patients. The results of the MMPI profiles showed
that the High-Sensitivity group included significantly more patients with the
Neurotic Triad pattern and no patients with the Conversion V pattern. The scores
of the hypochondriasis and hysteria scales were significantly lower in the High
Sensitivity group than in the Others group. CONCLUSIONS: This study indicated
that patients with chronic pain can be classified according to PTTs in non
injured sites and suggests that patients with High-Sensitivity have
characteristic psychological traits. Assessment of PTTs in non-injured sites
would be useful for evaluating the psychological condition of patients with
chronic pain.
PMID- 28507596
TI - Efficient whole-cell-catalyzing cellulose saccharification using engineered
Clostridium thermocellum.
AB - BACKGROUND: Cost-efficient saccharification is one of the main bottlenecks for
industrial lignocellulose conversion. Clostridium thermocellum naturally degrades
lignocellulose efficiently using the cellulosome, a multiprotein supermolecular
complex, and thus can be potentially used as a low-cost catalyst for
lignocellulose saccharification. The industrial use of C. thermocellum is
restrained due largely to the inhibition of the hydrolysate cellobiose to its
cellulosome. Although the supplementation of beta-glucosidase may solve the
problem, the production of the enzymes greatly complicates the process and may
also increase the cost of saccharification. RESULTS: To conquer the feedback
inhibition and establish an efficient whole-cell catalyst for highly efficient
cellulose saccharification, we constructed a recombinant strain of C.
thermocellum ?pyrF::CaBglA which produced a secretory exoglucanase CelS-bearing
heterologous BGL using a newly developed seamless genome editing system. Without
the extra addition of enzymes, the relative saccharification level of
?pyrF::CaBglA was stimulated by over twofolds compared to its parent strain ?pyrF
through a two-stage saccharification process with 100 g/L Avicel as the carbon
source. The production of reducing sugars and the relative saccharification level
were further enhanced to 490 mM and 79.4%, respectively, with increased cell
density. CONCLUSIONS: The high cellulose-degrading ability and sugar productivity
suggested that the whole-cell-catalysis strategy for cellulose saccharification
is promising, and the C. thermocellum strain ?pyrF::CaBglA could be potentially
used as an efficient whole-cell catalyst for industrial cellulose
saccharification.
PMID- 28507595
TI - Differential therapeutic effects of atomoxetine and methylphenidate in childhood
attention deficit/hyperactivity disorder as measured by near-infrared
spectroscopy.
AB - BACKGROUND: The stimulant methylphenidate (MPH) and the nonstimulant atomoxetine
(ATX) are the most commonly-prescribed pharmacological treatments for attention
deficit/hyperactivity disorder (ADHD). However, the drug-specific mechanism of
action on brain function in ADHD patients is not well known. This study examined
differences in prefrontal hemodynamic activity between MPH and ATX in children
with ADHD as measured by near-infrared spectroscopy (NIRS) using the Stroop color
word task. METHODS: Thirty children with ADHD participated in the present study.
We used 24-channel NIRS (ETG-4000) to measure the relative concentrations of
oxyhemoglobin in the frontal lobes of participants in the drug-naive condition
and those who had received MPH (n = 16) or ATX (n = 14) for 12 weeks.
Measurements were conducted every 0.1 s during the Stroop color-word task. We
used the ADHD RS-IV-J (Home Version) to evaluate ADHD symptoms. RESULTS:
Treatment with either MPH or ATX significantly reduced ADHD symptoms, as measured
by the ADHD RS-IV-J, and improved performance on the Stroop color-word task in
terms of number of correct words. We found significantly higher levels of
oxyhemoglobin changes in the prefrontal cortex of participants in the ATX
condition compared with the values seen at baseline (pre-ATX). In contrast, we
found no oxyhemoglobin changes between pre- and post-treatment with MPH.
CONCLUSIONS: The present study suggests that MPH and ATX have differential
effects on prefrontal hemodynamic activity in children with ADHD.
PMID- 28507597
TI - Low adherence to national guidelines for proton-pump inhibitor prescription in
patients receiving combination aspirin and anticoagulation.
AB - BACKGROUND: Aspirin, when used with concurrent anticoagulation, increases the
risk of gastrointestinal bleeding (GIB). Therefore, multisociety guidelines
recommend prophylactic proton-pump inhibitors (PPIs) for patients receiving
aspirin and anticoagulation. We aimed to determine rates and predictors of
adherence to these recommendations. METHODS: All adult inpatients discharged from
the hospital on aspirin and anticoagulation from July 2009 to June 2014 were
retrospectively evaluated for PPI prescription on discharge instructions. We used
univariate and multivariate logistic regression to test for predictors of PPI
prescription. RESULTS: A total of 2422 patients were discharged on aspirin and
anticoagulation; the mean age was 68 years and 53.2% were male; 42.2% were
prescribed a PPI at discharge. On univariate analysis, factors associated with
discharge PPI prescription included increased age (47.1% versus 37.9%), white
race (47.3% versus 37.1-40.2%), higher aspirin dose (55.1% versus 39.4%), being
married (46.2% versus 39.4%) and preadmission PPI use (96.6% versus 23.4%). On
multivariate analysis, significant predictors of discharge PPI prescription were
age 60-69 years [odds ratio (OR) 1.61] and 70-79 years (OR 1.48), and
preadmission PPI use (OR 120.03). Lower odds of discharge PPI prescription
included Medicaid (OR 0.55) or Medicare (OR 0.71) insurance, Spanish language (OR
0.63), and lower dose aspirin (81 mg) (OR 0.40). CONCLUSIONS: A total of 42.2% of
patients discharged on aspirin and anticoagulation were prescribed PPIs. Older
age and preadmission PPI use were predictive of PPI prescription, while
Medicaid/Medicare insurance, Spanish language, and lower dose aspirin decreased
the likelihood of discharge PPI prescription. This creates an opportunity to
improve primary GIB prevention through quality improvement interventions.
PMID- 28507598
TI - Thalidomide induces clinical remission and mucosal healing in adults with active
Crohn's disease: a prospective open-label study.
AB - BACKGROUND: Thalidomide is effective in inducing and maintaining clinical
remission in children and adolescents with refractory Crohn's disease (CD).
However, little is known about the efficacy and safety of thalidomide for adult
patients with CD. METHODS: We conducted a prospective open-label cohort study
between January 2013 and April 2015. A total of 47 adult patients with active CD
who were dependent/resistant or intolerant to corticosteroids and/or
immunomodulators or biologics received 50-100 mg of thalidomide daily. Primary
outcome was clinical remission evaluated at week 8. Endoscopic assessment was
performed at week 24 and defined as endoscopic response (decrease in Crohn's
Disease Endoscopic Index of Severity [CDEIS] score > 5 points from baseline CDEIS
of 6 or more), complete endoscopic remission (CDEIS score < 3), and mucosal
healing (MH) (no ulceration). RESULTS: A total of 47 adults with active CD were
enrolled. The clinical remission rate was 14.9% and 23.4% at week 4 and week 8,
but increased to 46.8% at week 12 and 53.2% at week 24 out of all the 47 patients
included (intention-to-treat analysis). Altogether 32 patients consented and
underwent ileocolonoscopy at week 24. The rate of endoscopic response and
complete endoscopic remission were 68.4% and 43.8%. MH (no ulceration) was
achieved in 28.1% of patients. Adverse events occurred in 27/47 (57.4%) patients
but necessitated therapy discontinuation in only 5/47 (10.6%) of patients.
CONCLUSIONS: Low-dose thalidomide was effective and tolerated for inducing and
maintaining clinical remission in adult patients with active CD, but the optimal
time frame for thalidomide to induce clinical remission may be longer than
previously appreciated and is probably optimal at 12 weeks. MH could reasonably
be achievable with thalidomide.
PMID- 28507599
TI - Comparison of relapse-free survival in gastric neuroendocrine carcinoma (WHO
grade 3) and gastric carcinoma.
AB - BACKGROUND: We compared relapse-free survival (RFS) in gastric neuroendocrine
carcinoma (WHO grade 3) and gastric carcinoma (GC). This is one of very few
studies that compare the prognosis of poorly differentiated neuroendocrine
carcinoma (WHO grade 3, G3 NEC) with that of GC. METHODS: Between 1996 and 2014,
63 patients were diagnosed with G3 NEC of the stomach and 56 with gastric
neuroendocrine tumors (NETs) with GC at Asan Medical Center in Seoul, Korea. We
also randomly selected 762 patients diagnosed with GC between 1999 and 2008.
RESULTS: Patients with G3 NEC tumors that invaded the muscularis propria or
shallower had poorer RFS than those with GC of the same type, while G3 NEC that
invaded the subserosa or deeper had similar RFS to GC of that type. Patients
diagnosed with G3 NEC with N0 or N2 had poorer RFS than the corresponding
patients with GC, while those who had G3 NEC with N1 or N3 had similar RFS to the
corresponding patients with GC. G3 NEC patients had poorer RFS than well
differentiated, moderately differentiated and poorly differentiated GC patients,
while G3 NEC patients had similar RFS to that of those with signet ring cell
carcinoma (SRC). In addition, patients with G3 NEC of stages I or IIa had poorer
RFS than those with corresponding GC, while G3 NEC stage IIb or greater had
similar RFS to the corresponding GC. CONCLUSIONS: Non-advanced G3 NEC showed
poorer RFS than GC excluding SRC, while advanced G3 NEC has a similar RFS to that
of GC without SRC. Therefore, we recommend that patients with non-advanced G3 NEC
of the stomach be given a more aggressive treatment and surveillance than those
with non-advanced GC excluding SRC.
PMID- 28507601
TI - End of treatment RNA-positive/sustained viral response in an individual with
acute hepatitis C virus infection treated with direct-acting antivirals.
PMID- 28507600
TI - Insights into the role of the intestinal microbiota in colon cancer.
AB - The intestinal microbiota consists of a dynamic organization of bacteria,
viruses, archaea, and fungal species essential for maintaining gut homeostasis
and protecting the host against pathogenic invasion. When dysregulated, the
intestinal microbiota can contribute to colorectal cancer development. Though the
microbiota is multifaceted in its ability to induce colorectal cancer, this
review will focus on the capability of the microbiota to induce colorectal cancer
through the modulation of immune function and the production of microbial-derived
metabolites. We will also explore an experimental technique that is
revolutionizing intestinal research. By elucidating the interactions of microbial
species with epithelial tissue, and allowing for drug screening of patients with
colorectal cancers, organoid development is a novel culturing technique that is
innovating intestinal research. As a cancer that remains one of the leading
causes of cancer-related deaths worldwide, it is imperative that scientific
findings are translated into the creation of effective therapeutics to treat
colorectal cancer.
PMID- 28507604
TI - Health-related quality of life outcomes from botulinum toxin treatment in
hemifacial spasm.
AB - BACKGROUND: Although botulinum neurotoxin (BoNT) injections may alleviate
involuntary muscle contractions in hemifacial spasm substantially, it is less
clear whether the motor effect would translate into improvements of health
related quality of life (HR-QoL). METHODS: In this open-label clinical
observational study, we characterized outcomes on HR-QoL in terms of the EuroQol
(EQ-5D-5L) from BoNT in a prospective cohort of patients with hemifacial spasm (n
= 73). Additionally, we characterized appendicular motor and nonmotor signs on
motor symptom improvement, depressive symptoms, pain and sleep quality. Patients
were assessed at the end of a regular 3-month period from last injection
(timepoint1) and 4 weeks after the reinjection of BoNT (timepoint2). RESULTS:
Patients showed improved HR-QoL on the EQ-VAS (visual analogue scale) at
timepoint2 compared with timepoint1. Moreover, we identified, that impairments in
HR-QoL at timepoint1 correlated with life satisfaction and depressive symptoms,
respectively. However, these associated variables did not predict the therapeutic
effect. Instead, EQ-VAS at timepoint1 accounted for 34.5% of the variance of EQ
VAS improvement expressed as the difference between timepoint2 and timepoint1.
CONCLUSION: Our study supports HR-QoL improvements in hemifacial spasm and the
value of generic HR-QoL measures to estimate therapeutic outcome. However, the
findings should be considered descriptive, and future high quality trials are
needed for confirmatory purposes in order to refine treatment referral in
hemifacial spasm with respect to QoL.
PMID- 28507603
TI - Fingolimod initiation in multiple sclerosis patients is associated with potential
beneficial cardiovascular autonomic effects.
AB - BACKGROUND: Fingolimod slows heart rate (HR) due to vagomimetic effects and might
cause additional cardiovascular autonomic changes. While the time course of HR
changes is well described, the extent and course of cardiovascular autonomic
changes upon fingolimod initiation has not yet been evaluated. This study,
therefore, intended to assess cardiovascular autonomic changes during the first 6
h after fingolimod initiation. METHODS: In 21 patients with relapsing-remitting
multiple sclerosis (RRMS), we recorded respiration (RESP), electrocardiographic
RR interval (RRI), systolic and diastolic blood pressure (BPsys, BPdia) at rest,
before and 0.5, 1, 2, 3, 4, 5, and 6 h after fingolimod initiation. We calculated
parameters of total autonomic modulation [RRI standard deviation (RRI-SD), RRI
coefficient of variation (RRI-CV), RRI-total powers], mainly sympathetic cardiac
modulation [RRI low frequency (LF) powers], sympathetic BP modulation (BPsys-LF
powers), parasympathetic modulation [square root of the mean squared difference
of successive RRIs (RMSSD), RRI high frequency (HF) powers], sympatho-vagal
cardiac balance (RRI-LF/HF ratios), and baroreflex sensitivity (BRS). We compared
parameters between the eight measurements [analysis of variance (ANOVA) or
Friedman test with post-hoc analysis; significance: p < 0.05]. RESULTS: After
fingolimod initiation, RESP, BPsys, and BPsys-LF powers remained unchanged while
RRIs, RRI-CV, RRI-SD, RRI-total powers, RRI-LF powers, RMSSD, RRI-HF powers, and
BRS increased after 1 h and rose to peak values occurring after 5, 1, 2, 2, 1, 4,
4, and 4 h, respectively. After 3 h, BPdia had decreased significantly and was
lowest after 5 h. RRI-LF/HF ratios decreased to a nadir after 4 h. CONCLUSIONS:
The increases in parasympathetic and overall cardiac autonomic modulation and in
BRS seen with fingolimod initiation are theoretically beneficial for the MS
patient's cardiovascular system. However, long-term studies must show whether
these effects persist or are attenuated (e.g. due to S1P1 receptor down
regulation upon continued fingolimod therapy).
PMID- 28507605
TI - Diclofenac potassium for oral solution (CAMBIA(r)) in the acute management of a
migraine attack: clinical evidence and practical experience.
AB - Migraine headache affects about 12% of Western populations and is the third most
common disease worldwide (sixth in terms of disability). In 1993, triptans were
introduced in the United States as a new treatment for managing migraine attacks,
but their use is limited by lack of response and safety concerns in some
patients. Treatment options for patients with migraine who fail or cannot
tolerate triptans include switching to another medication or adding an adjunctive
medication. Desirable characteristics reported by patients for acute treatment of
migraine attacks include complete pain relief, fast onset of action, and no pain
recurrence. Diclofenac is a nonsteroidal anti-inflammatory medication that has
been established as effective for acute treatment of migraine by the American
Headache Society based on available evidence. Diclofenac potassium for oral
solution is rapidly absorbed, achieving maximal plasma concentrations in 15 min,
which coincides with a rapid onset of effect. In a comparison of diclofenac
potassium for oral solution with diclofenac potassium tablets, the solution
achieved a significant reduction in headache intensity beginning at 15 min
compared with 60 min for the tablet. Across randomized clinical trials,
approximately 25% of patients were pain free 2 h after administration of
diclofenac oral solution and the effects were maintained over a 24-h period.
Diclofenac potassium for oral solution is well tolerated; the most common adverse
events are dizziness and gastrointestinal complaints, with incidences similar to
placebo. No serious adverse events have been reported in clinical trials of
diclofenac potassium for oral solution in the acute treatment of migraine.
Diclofenac oral solution may offer rapid and sustained pain relief for patients
who do not achieve pain resolution with other medications. In addition, patients
who experience central sensitization with allodynia may benefit from the
cyclooxygenase-blocking activity of diclofenac, which is needed in this advanced
phase of migraine.
PMID- 28507606
TI - Transcription and chromatin determinants of de novo DNA methylation timing in
oocytes.
AB - BACKGROUND: Gametogenesis in mammals entails profound re-patterning of the
epigenome. In the female germline, DNA methylation is acquired late in oogenesis
from an essentially unmethylated baseline and is established largely as a
consequence of transcription events. Molecular and functional studies have shown
that imprinted genes become methylated at different times during oocyte growth;
however, little is known about the kinetics of methylation gain genome wide and
the reasons for asynchrony in methylation at imprinted loci. RESULTS: Given the
predominant role of transcription, we sought to investigate whether transcription
timing is rate limiting for de novo methylation and determines the asynchrony of
methylation events. Therefore, we generated genome-wide methylation and
transcriptome maps of size-selected, growing oocytes to capture the onset and
progression of methylation. We find that most sequence elements, including most
classes of transposable elements, acquire methylation at similar rates overall.
However, methylation of CpG islands (CGIs) is delayed compared with the genome
average and there are reproducible differences amongst CGIs in onset of
methylation. Although more highly transcribed genes acquire methylation earlier,
the major transitions in the oocyte transcriptome occur well before the de novo
methylation phase, indicating that transcription is generally not rate limiting
in conferring permissiveness to DNA methylation. Instead, CGI methylation timing
negatively correlates with enrichment for histone 3 lysine 4 (H3K4) methylation
and dependence on the H3K4 demethylases KDM1A and KDM1B, implicating chromatin
remodelling as a major determinant of methylation timing. We also identified
differential enrichment of transcription factor binding motifs in CGIs acquiring
methylation early or late in oocyte growth. By combining these parameters into
multiple regression models, we were able to account for about a fifth of the
variation in methylation timing of CGIs. Finally, we show that establishment of
non-CpG methylation, which is prevalent in fully grown oocytes, and methylation
over non-transcribed regions, are later events in oogenesis. CONCLUSIONS: These
results do not support a major role for transcriptional transitions in the time
of onset of DNA methylation in the oocyte, but suggest a model in which sequences
least dependent on chromatin remodelling are the earliest to become permissive
for methylation.
PMID- 28507607
TI - Gene variants in the FTO gene are associated with adiponectin and TNF-alpha
levels in gestational diabetes mellitus.
AB - BACKGROUND: Obesity may have a role in the development of gestational diabetes
mellitus (GDM). Single-nucleotide-polymorphisms (SNPs) of the FTO (fat mass and
obesity associated) gene have been associated with obesity. The aim of this study
was to investigate SNPs rs8050136, rs9939609, and rs1421085 of the FTO gene in
women with GDM and their associations with maternal pre-pregnancy weight and body
mass index, gestational weight gain and mediators of insulin resistance in GDM
like leptin, adiponectin, ghrelin and tumor necrosis factor-alpha (TNF-alpha),
compared with healthy pregnant controls. METHODS: 80 women with GDM and 80 women
with normal pregnancy were considered for the present study. Genotyping of
selected SNPs in all study subjects was done using the Taq-Man assay and the
adipokines and ghrelin were measured by immunoassays. Chi square test, odds
ratios (OR) and their respective 95% confidence intervals were used to measure
the strength of association between FTO SNPs and GDM. RESULTS: There was no
association among FTO SNPs and GDM. Interestingly, in GDM group, women carrying
the risk alleles of the three SNPs had increased TNF-alpha, and decreased
adiponectin levels; these associations remained significant after adjusting for
pre-gestational body weight and age. Moreover, the risk allele of rs1421085 was
also associated with increased weight gain during pregnancy. CONCLUSIONS: The FTP
SNPs rs8050136, rs9939609, and rs1421085 are not a major genetic regulator in the
etiology of GDM in the studied ethnic group. However, these SNPs were associated
with adiponectin and TNF-alpha concentrations in GDM subjects.
PMID- 28507608
TI - Roles of fasting and postprandial blood glucose in the effect of type 2 diabetes
on central arterial stiffness: a 5-year prospective community-based analysis.
AB - BACKGROUND: Cardiovascular disease constitutes a major challenge for the health
of community-dwelling population, it is essential to delay the development of
atherosclerosis. However, long-term prospective studies analyzing the effect of
type 2 diabetes (T2D) on central arterial stiffness are lacking, and roles of
fasting and postprandial blood glucose (FBG and PBG) in this effect are
controversial. Purpose of the current analysis was to investigate the effect of
T2D on central arterial stiffness during the 5 years of follow-up, and explore
whether both FBG and PBG were determinants of this effect in Chinese community
dwelling population. METHODS: The current analysis involved 898 individuals with
carotid-femoral pulse wave velocity (cfPWV) <=12 m/s. Central arterial stiffness
was assessed by standard cfPWV at baseline and follow-up. RESULTS: Incidence of
cfPWV >12 m/s was 21.3% (102 participants). Participants without T2D had an
increase of cfPWV with a median of 0.6 m/s, whereas participants with T2D had an
increase of cfPWV with a median of 1.2 m/s (p = 0.007). T2D had an independent
effect on increased cfPWV in multivariate Logistic regression models (p < 0.05
for all). Elevated levels of both FBG and PBG determined the independent effect
on increased cfPWV in multivariate linear regression models (p < 0.05 for all).
CONCLUSIONS: Type 2 diabetes had an independent effect on the development of
central arterial stiffness in Chinese community-dwelling population. Both FBG and
PBG should be responsible for the development of central arterial stiffness and
treated as the targets of glycemic control.
PMID- 28507609
TI - Depression and alexithymia on weight perception in patients with metabolic
syndrome and type 2 diabetes.
AB - BACKGROUND: Obesity's increasing follows decreased perception of weight status in
obese persons, mainly female, undergoing age-related changes. OBJECTIVE: To study
weight perception and psychological alterations associated to MS and T2DM.
METHODS: 200 patients selected from Metabolic Syndrome Outpatient Clinic of
University of Campinas. Instruments: Beck Depression and Beck Anxiety
Inventories', Toronto Alexithymia Scale-26s, questionnaire and data from reports.
Approved by Unicamp Research Ethic Committee. RESULTS: Patients aged 18-40 years
perceived their weight higher than actual (A < D) (p = 0.0272), amongst untreated
hypertensive (p = 0.037). >=41 years old patient's subdivided into A = D and A >
D. A = D had 4.3 more chances to be alexithymic than A < D. 35% of A < D accepted
their physical appearance, contrarily A = D (66%) and A > D (69%) (p = 0.0018).
50% of A < D felt offended by social aggression due to their weight; A = D (20%)
and A > D (34%) (p = 0.007). 3.6 more chances of A > D than A < D using anti
hypertensive drugs (p = 0.021) (>=41 years old) and 3.5 more chances to perceive
A = D (41-60 years old) (p = 0.023). A = D presented 3.8 more chances of
depression than A < D and 4.3 more chances of alexithymia than A < D (62% of 41
60 year-old patients with higher cholesterol, mainly LDL and hyper
triglycerides). A = D with alexithymia, partially linked with higher cholesterol,
suggests neuroinflammation due to hypertriglycerides. Females, who declared had
been anteriorly made diet as treatment to lose weight were exactly those who
perceived their weight A > D (45%, p = 0.0091). CONCLUSIONS: Age as a period of
development, in which cultural influences occurs, was a factor in weight
misperception. A < D and A > D were distinct in age, history of obesity and BMI.
PMID- 28507610
TI - Improving Patient Safety in Hospitals through Usage of Cloud Supported Video
Surveillance.
AB - BACKGROUND: Patient safety in hospitals is of equal importance as providing
treatments and urgent healthcare. With the development of Cloud technologies and
Big Data analytics, it is possible to employ VSaaS technology virtually anywhere,
for any given security purpose. AIM: For the listed benefits, in this paper, we
give an overview of the existing cloud surveillance technologies which can be
implemented for improving patient safety. MATERIAL AND METHODS: Modern VSaaS
systems provide higher elasticity and project scalability in dealing with real
time information processing. Modern surveillance technologies can prove to be an
effective tool for prevention of patient falls, undesired movement and tempering
with attached life supporting devices. Given a large number of patients who
require constant supervision, a cloud-based monitoring system can dramatically
reduce the occurring costs. It provides continuous real-time monitoring,
increased overall security and safety, improved staff productivity, prevention of
dishonest claims and long-term digital archiving. CONCLUSION: Patient safety is a
growing issue which can be improved with the usage of high-end centralised
surveillance systems allowing the staff to focus more on treating health issues
rather that keeping a watchful eye on potential incidents.
PMID- 28507611
TI - The Impact of Extended Typing On Red Blood Cell Alloimmunization in Transfused
Patients.
AB - BACKGROUND: Red blood cell (RBC) alloimmunization is still an actual problem in
our transfusion practice. In 2011, in addition to the regular ABO/D blood group
typing, phenotyping for Rh (C, c, E, e) and Kell antigens was introduced for
blood donors and patients undergoing blood transfusion. Our aim was to evaluate
the impact of the extended RBC typing and donor/recipient matching on the
incidence of RBC alloimmunization. METHODS: A retrospective comparative study was
conducted by reviewing RBC request records for about 36,000 patients transfused
with RBC in the period from 2013 to 2015 in comparison to the similar study
conducted on 47,000 transfused patients in the period from 2005 to 2008. Pre
transfusion serologic testing data were retrieved for analysis. Blood samples
with positive antibody screening and positive cross-match were further subjected
to antibody identification. All the tests were performed using column
agglutination technique (CAT) with ID-cards and reagents from DiaMed in both
studies. RESULTS: Irregular RBC alloantibodies were detected in 116 (0.32%) out
of 36,000 transfused patients. Multiple transfusions (15.8 units/patient) were
given to 450 patients from which 79 (17.5%) had RBC allontibodies. The incidence
of RBC alloimmunisation in the rest of the 35,550 transfused patients from which
37 had RBC alloantibodies was 0.10%. A total of 117 alloantibodies were
identified in 96 out of the 116 patients with irregular RBC antibodies. Their
specificity was as fallows: anti-E (25.6%), -C (6.0%), -c (8.5%), -e (0.85%), -Cw
(5.1%), -K (12.8%), -Fya (10.2%), -Fyb (2.5%), -Jka (7.7%), -Jkb (2.5%), -M
(9.4%), -S (1.7%), -s (0.85%), -Lua (1.7%), -Leb (3.4%) and anti-Leb (0.85%).
Multiple antibodies were identified in 22 of the transfused patients out of which
15 (68.2%) received multiple transfusions. Anti-E was the most common antibody
found in more of the 50% of the multiple antibody cases. CONCLUSIONS: The overall
incidence of RBC alloimmunization in transfused patients decreased from 0.51%
which was the estimated incidence for the period before the introduction of the
extended RBC typing (2005-2008) to 0.32% (2013-2015). This is due to the
decreased incidence of RBC alloimmunization in the multiply transfused patients
from 33.9% to 17.5% respectively. The current frequency of anti-E (25.6%) and -K
(12.8%) antibodies in transfused patients are significantly lower than their
previous estimated frequencies of 30.4% and 24.0% respectively, as well as the
overall frequency of RBC antibodies to Rh+Kell antigens which decreased from
72.4% to 53.8%. Extended donor-recipient matching for C, c, E, e and Kell
antigens has proved a beneficial effect on the incidence of RBC alloimmunization
in multiply transfused patients.
PMID- 28507612
TI - Pattern of Injuries in Fatal Motorcycle Accidents Seen in Lagos State University
Teaching Hospital: An Autopsy-Based Study.
AB - BACKGROUND: Deaths from motorcycle accident injuries have remained a major public
health issue in Nigeria over the years. AIM: The study is to determine the age
and gender distribution of the victims and to identify the cause of death and the
anatomical pattern of injuries seen. METHODOLOGY: This is a 5-year autopsy-based
study of all motorcycle accident deaths seen in Lagos State University Teaching
Hospital between December 2009 and November 2014. The data were retrieved from
autopsy reports, hospital case notes extracts from police diary and were analysed
using SPSS version 20. RESULTS: Motorcycle accidents accounted for 156 (2.8%) of
all the autopsies done (5,661), and 156 (18.4%) of all Road Traffic Accidents
(RTA) autopsies (849) performed over the study period, with a male: female ratio
of 6:1. The peak age of victims was 31-40 years (30.9%). Head injuries accounted
for most (41.4%) of the injuries seen, and the majority of the victims died of
craniocerebral injury 53 (50.7%). CONCLUSION: This study showed that males in the
fourth decade of life are the major victims of motorcycle accident death. The
majority of the victims were the rider of the motorcycle. Most of them died of
the craniocerebral injury.
PMID- 28507613
TI - Correlation between Soil-Transmitted Helminths Infection and Serum Iron Level
among Primary School Children in Medan.
AB - BACKGROUND: The latest estimates indicate that more than 2 billion people
worldwide are infected by Soil-Transmitted Helminths (STH). The burden of STH
infection is mainly attributed to the chronic effect on health and quality of
life of those infected. It is also contributed to micronutrient deficiencies such
as iron-deficiency anaemia. The prevalence of worm infection in Public Primary
School students in Medan was quite high (40.3%), and 33.3% was anaemic in the
latest study. AIM: To determine the correlation between STH infection with serum
iron (SI) level on primary school children, as well as to determine the
prevalence of SI level and worm infection, and the type of worm that infects the
most of them. METHODS: This study was conducted in the cross-sectional method.
Consecutive sampling technique was used and a total of 132 students age 8-12
years old were included. The study took places in Public Primary School 060925
Amplas, Medan and 101747 Hamparan Perak, Deli Serdang throughout May-October
2016. Fisher Exact test was used to analyse the correlation between STH infection
and SI level. RESULTS: The prevalence of STH infection was 7.6%, and low SI was
11.4%. CONCLUSION: There was no significant correlation between STH infection and
SI level (P = 0.317). The prevalence of low SI level was not significantly
dependent on STH infection (RP = 1.877, 95% CI = 0.481-7.181).
PMID- 28507614
TI - Functional Pattern of Increasing Concentrations of Brain-Derived Neurotrophic
Factor in Spiral Ganglion: Implications for Research on Cochlear Implants.
AB - BACKGROUND: As previously various studies have suggested application of brain
derived neurotrophic factor (BDNF) may be considered as a promising future
therapy for hearing deficits, in particular for the improvement of cochlear
neurone loss during cochlear implantation. AIM: The present study's aim was to
establish the upper threshold of the concentration of BDNF in Naval Medical
Research Institute (NMRI) mice spiral ganglion outgrowth. METHODS: Spiral
ganglion explants were prepared from post-natal day 4 (p4) (NMRI) mice of both
sexes under the approval and guidelines of the regional council of Hearing
Research Institute Tubingen. RESULTS: Spiral ganglion explants were cultured at
postnatal days 4 in the presence of different concentrations of BDNF as described
under methods. We chose an age of postnatal day (P4) and concentrations of BDNF
0; 6; 12.5; 25 and 50 ng/ml. Averaged neurite outgrowth is measured in 4
different cultures that were treated with different concentrations. Results show
that with increasing concentrations of BDNF, the neurite density increases.
CONCLUSION: The present finding show evidence that BDNF has a clear incremental
effect on the number of neurites of spiral ganglia in the prehearing organ, but
less on the neurite length. The upper threshold of exogenous BNDF concentration
on spiral ganglion explant is 25 ng/ml. This means that concentration beyond this
level has no further incremental impact. Therefore our suggestion for hydrogel
concentration in NMRA mice in future research should be 25 ng/ml.
PMID- 28507615
TI - No Association between 25 (OH) Vitamin D Level And Hypothyroidism among Females.
AB - AIM: The aim was to investigate serum vitamin D (25-OH) level among females with
hypothyroidism. MATERIALS AND METHODS: A case-control study (58 in each arm) was
conducted in Arar Central Hospital, Kingdom Saudi Arabia. The cases were females
with hypothyroidism, and healthy females were controls. TSH, thyroid hormones:
Free T3 (FT3) and Free T4 (FT4) and haemoglobin levels were measured in all
participants. Serum vitamin D (25-OH) level was measured using the
spectrophotometry. RESULTS: While there was no significant difference in the age
and haemoglobin level, body mass index (BMI) was significantly higher in the
cases. Compared with the controls, cases had significantly higher TSH, had
significantly lower T4, and there was no significant difference in FT3 and 25
(OH) vitamin D, [16.1 (8.8-26.7) vs. 14.0 (9.5-20.3 ng/ml; P = 0.577]. Linear
regression showed no association between, age, BMI, haemoglobin, TSH, FT3, FT4
and the log of 25 (OH) vitamin D levels. CONCLUSION: There was no significant
difference in vitamin D level among females with hypothyroidism and healthy
controls.
PMID- 28507616
TI - Leptin and Lipid Profile in Overweight Patient with Type 1 Diabetes.
AB - AIM: To evaluate leptin and lipid profile in overweight patients with type 1
diabetes. PATIENTS AND METHODS: The study included 50 overweight patients with
type 1 diabetes and 50 age and sex matched healthy controls. Blood samples were
taken for evaluation of glycosylated haemoglobin, lipid profile and leptin. Also,
urine samples were taken for evaluation of albumin/creatinine ratio. RESULTS:
Leptin level was significantly lower in overweight with type 1 diabetes and
showed a significant positive correlation with hip circumference and body mass
index and negative correlation with glycosylated haemoglobin (HbA1c). Leptin
level was significantly lower in overweight diabetic patients with HbA1c > 7.5 %.
The best cut-off point between overweight diabetic group and control group
regarding leptin levels was found at 16.9 (ng/ml) with a sensitivity of 68% and
specificity of 56%, area under the curve 0.623. CONCLUSION: Leptin levels were
found to be low in overweight patients with type 1 diabetes and showed
correlation with the body mass index and hip circumference. LDL was significantly
higher while HDL was significantly lower in the diabetic, overweight group
indicating increased risk of cardiovascular disease. Leptin level in overweight
diabetic patients might be related to the metabolic control.
PMID- 28507617
TI - Serum VEGF Levels in Helicobacter pylori Infection and Correlation with
Helicobacter pylori cagA and vacA Genes.
AB - BACKGROUND: Helicobacter pylori vacA and cagA genes are associated with higher
virulence. Vascular Endothelial Growth Factor (VEGF) is one important marker for
neo-angiogenesis. AIM: The purpose of this study was to investigate the
relationship between VEGF serum levels with cagA and vacA genes in H. pylori
infection. METHODS: A cross-sectional study was done on eighty patients that
consecutive admitted to endoscopy unit. The diagnosis of H. pylori infection was
based on rapid urease test. Serum samples were obtained to determine circulating
VEGF level. Polymerase chain reaction was done to examine H. pylori vacA and cagA
genes. Data analysis were carried-out using SPSS version 22. RESULTS: A total of
80 patients were examined. There were 45 (56.3%) patients infected with
Helicobacter pylori. There were 33 (73.3%) patients with H. pylori cagA positive.
Serum VEGF levels in patients with the H. pylori positive were significantly
higher compared to the patients that have no H. pylori. Serum levels of VEGF were
significantly higher in cagA positive than negative. CONCLUSION: Serum VEGF level
is correlated with H. pylori infection and its virulence status. The more
virulence of H. pylori, cagA gene, the higher serum VEGF levels were found.
PMID- 28507618
TI - Correlation between Soil Transmitted Helminth Infection and Eosinophil Levels
among Primary School Children in Medan.
AB - BACKGROUND: Soil Transmitted Helminth infection is one of most prevalent health
problems worldwide, especially in environments with poor sanitation. Based on
World Health Organisation (WHO) data, more than 2 billion people, or 24% of the
world's population, are infected with intestinal parasite. The highest prevalence
is located in areas of poor sanitation and unsafe water supplies. In Indonesia,
the prevalence of parasite infections is 15% of the entire population. AIM: The
purpose of this study was to determine the relationship between Soil Transmitted
Helminth infection on levels of eosinophils among primary school children. In
addition, this study also aimed to determine the prevalence of different types of
worm infections and the levels of eosinophils in children infected with worms.
MATERIAL AND METHODS: This study was analytic observational using a cross
sectional method. The sampling technique was consecutive and in total 132 samples
was obtained. The study involved primary school children in Amplas Medan and
Hamparan Perak, Deli Serdang through May to October 2016. Univariate analysis was
performed to determine STH infection prevalence and bivariate analysis was used
to find the correlation between STH infection and eosinophil levels through a Chi
square (chi2) test. RESULTS: The results showed that the prevalence of Soil
Transmitted Helminth was 7.6%. The most common types of STH infection were 3.8%
with Trichuris trichiura and 3% with Ascaris lumbricoides. A significant
correlation was found between Parasite infection and eosinophil levels
(Contingency Coefficient (C) = 0.2, chi2 = 5.3, p = 0.021) and the risk of STH
infection that caused eosinophilia or increased eosinophil levels in the children
with a Prevalence Ratio (PR) of 1.56 (Confidence Interval (CI) 95%: 1.10-2.22).
CONCLUSION: It is recommended that schools at similar risk improve and maintain
hygiene and healthy behaviour in the school environment and that parents and
teachers pay greater attention to the cleanliness of their children.
PMID- 28507620
TI - Expression of E-Cadherin/Beta-Catenin in Epithelial Carcinomas of the Thyroid
Gland.
AB - BACKGROUND: The aberrant activation of Wnt signalling pathway may be a common
denominator for the development of thyroid tumorigenesis. It was announced that
the loss of E-cadherin rather than beta-catenin mutation represents a crucial
event in determining the degree of differentiation of thyroid carcinomas. AIM:
The aim of the study was to evaluate the expression of E-cadherin and beta
catenin in the thyroid cancer tissue and to correlate these data with some
histological and clinical parameters of the tumours. MATERIAL AND METHODS: We
investigated 112 patients, having thyroid tumours - papillary, follicular,
anaplastic and oncocytic carcinomas immunohistochemically with antibodies against
E-cadherin and beta-catenin. Survival analyses were done. RESULTS: E-cadherin
expression was focally retained in the tumour cell membranes and the tumour cell
cytoplasm of the papillary, follicular and oncocytic thyroid cancers, weather in
anaplastic cancers it was almost lost (p = 0.0042, and p = 0.019, respectively,
Fisher's Exact Test). The expression of beta-catenin in tumour cytoplasm and
membrane in papillary cancers was higher as compared to that in the other tumours
(p = 0.111, and p = 0.0104, respectively). CONCLUSION: Not surprisingly, the
presence of aberrant expression of E-cadherin and beta-catenin in thyroid cancer
has been associated with better patients' prognosis and better differentiated
tumour histology.
PMID- 28507619
TI - Expression of ERG Protein and TMRPSS2-ERG Fusion in Prostatic Carcinoma in
Egyptian Patients.
AB - AIM: Prostate cancer (PCa) is the second most common cancers in men worldwide.
Its incidence can be influenced by several risk factors including genetic
susceptibility. Therefore the search for the expression of a certain gene (ERG)
and its rearrangement could give us clues for proper identification of PCa. And
the study of ERG expression and its comparison to FISH in Egyptian patients can
show whether ERG immunophenotype could be used instead of FISH, as it is cheaper.
MATERIALS AND METHODS: This study was performed on 85 cases of PCa, showing 30
cases with HGPIN and 30 cases of prostatic hyperplasia. All were
immunohistochemistry stained using ERG monoclonal rabbit antihuman antibody was
used (clone: EP111). FISH analysis was performed in 38 biopsies of PCa cases to
detect TMRPSS2-ERG rearrangement using the FISH ZytoLight TriCheck Probe (SPEC
TMRPSS2-ERG). RESULTS: ERG expression was found in 26% of PCa cases and 20% of
HGPIN cases. FISH analysis showed fusion of 21 cases of PCa (out of 22 cases
showing ERG immunoexpression). CONCLUSION: Our findings emphasise that only
malignant and pre-malignant cells and not benign cells from the prostate stain
positive. ERG expression may offer a simpler, accurate and less costly
alternative for evaluation of ERG fusion status in PCa.
PMID- 28507621
TI - Expression of FGFR3 Protein and Gene Amplification in Urinary Bladder Lesions in
Relation to Schistosomiasis.
AB - BACKGROUND: Bladder cancer represents the fifth most common malignancy worldwide
and a major cause of cancer-related morbidity and death. Incidence and mortality
rates have remained relatively constant over the past four decades. Urothelial
bladder cancers have identified multiple risk factors. AIM: We aimed at
evaluating the expression of the FGFR3 protein and gene amplification in the
urothelial cells of neoplastic and non-neoplastic urothelial lesions of the
urinary bladder, and correlation with tumour grade, stage and associated
bilharziasis. MATERIAL AND METHODS: One hundred and five different urinary
bladder lesions were studied, including 15 cystitis cases (9 bilharzial and 6 non
bilharzial cystitides), 75 urothelial carcinoma cases (18 bilharzial associated
and 57 non-bilharzial associated) and 15 squamous cell carcinoma associated with
bilharziasis, beside 5 control cases. Data concerning age, sex, tumour grade,
stage, and associated bilharziasis were obtained. Each case was studied for FGFR3
expression, and FISH technique was applied on forty malignant cases that show
high protein expression. RESULTS: The highest incidence of cystitis was in the
fourth decade while of bladder cancer was in the seventh decade. Tumour grade was
correlated significantly with tumour stage. FGFR3 correlates significantly with
tumour grade, stage and with a bilharzial infestation. FGFR3 gene amplification
was reported mainly in low grade and NNMBIC tumours. CONCLUSIONS: FGFR3
overexpression in malignant cases was significantly higher than in chronic
cystitis. FGFR3 gene amplification was reported mainly in low grade and NNMBIC
tumours. FGFR3 may be further studied as a subject for target therapy of bladder
cancer.
PMID- 28507622
TI - Prognostic Value of Vascular Endothelial Growth Factor A in the Prediction of the
Tumor Aggressiveness in Clear Cell Renal Cell Carcinoma.
AB - BACKGROUND: Clear cell renal cell carcinoma (CCRCC) is the most predominant renal
tumour with unpredictable tumour behaviour. The aim of the study is to
investigate the prognostic value of vascular endothelial growth factor A (VEGF-A)
expression in CCRCC and to correlate it with other histological parameters as
well as with patient's survival. MATERIAL AND METHODS: Tumour blocks were taken
from 40 patients with histopathology diagnosis of CCRCC and tissue block from 20
normal kidneys as a control group were examined using the immuno-histochemical
staining for VEGF-A. RESULTS: The VEGF A expression in CCRCC was significantly
higher than in the normal kidney tissues (U' = 720, P < 0.0001). VEGF A
expression values in CCRCC were positively correlated with Disease Free Survival
(r = 0.335, P = 0.034) and the tumor necrosis degree (r = 0.181, P = 0.262). VEGF
A expression values in CCRCC did not correlate with CD 31 expression (r = -0.09,
P = 0.549), and Progression Free Survival (r = -0.07, P = 0.838). VEGF A
expression values in CCRCC were negatively correlated with the tumor nuclear
grade (r = -0.161, P = 0.318); the pathological tumor stage (r = -0.371, P =
0.018); the tumor size (r = -0.361, P = 0.022); the degree of tumor hemorrhage (r
= -0.235, P = 0.143); and Cancer Specific Survival (r = -0.207, P = 0.713).
CONCLUSIONS: VEGF-A expression can be used to stratify advanced and metastatic
CCRCC patients into low-benefit and high-benefit groups. Based on this study
outcome it would be useful to perform IHC staining for VEGF-A expression in all
patients with advanced and metastatic CCRCC.
PMID- 28507623
TI - Association between ABO and Rh Blood Groups and Risk of Preeclampsia: A Case
Control Study from Iran.
AB - AIM: Preeclampsia (PE) is a major cause of maternal and neonatal morbidity and
mortality. There is a genetic component in the development of PE with estimated
heritability around 0.47. Several studies have investigated the association
between maternal ABO blood groups (OMIM 110300) and risk of PE, with
contradictory results have emerged. Considering that there is no study in this
filed from Iranian population, the present case-control study was carried out at
Shiraz (south-west Iran). MATERIAL AND METHODS: In this study 331 women; 121
pregnant with PE and 210 normotensive pregnant women were included. Using blood
group O (for ABO blood groups) or Rh+ (for Rh blood groups) as a reference, odds
ratios (ORs) and its 95% confidence intervals (95% CI) of PE risk were estimated
from logistic regression analysis. RESULTS: Although the A (OR = 0.67, 95% CI =
0.39-1.17, P = 0.165), B (OR = 0.86, 95% CI = 0.48-1.53, P = 0.615) and AB (OR =
1.14, 95% CI = 0.37-3.45, P = 0.812) phenotypes showed lower risks compared with
the O blood group, statistical analysis indicated that there was no significant
association between ABO phenotypes and risk of PE. The frequency of Rh- phenotype
was higher among PE patients compared with the control group. However, the
association was not significant (OR = 1.79, 95% CI = 0.69-4.65, P = 0.229).
Adjusted ORs for age of participants and parity did not change the above
mentioned associations. CONCLUSION: Our present findings indicate that there is
no association between ABO and Rh blood groups and risk of PE in Iranian
population.
PMID- 28507624
TI - The Prevalence and Risk Factors of Osteoporosis among a Saudi Female Diabetic
Population.
AB - AIM: This study aimed to assess the prevalence and determinants of osteoporosis
[lumbar spine (LS) and femoral neck (FN)] among patients with type 2 diabetes at
King Salman Hospital. MATERIALS AND METHODS: One hundred seventy patients with
type 2 diabetes were enrolled in this cross-sectional study in the period from
the 1st of January until the 1st of July 2015. Patient selection was based on
self-report of the previous diagnosis by a physician, being on an antidiabetic
agent, or a fasting glucose of 126 mg/dl as per the American Diabetes Association
criteria. A dual energy X-ray absorptiometry scan with the bone mineral density
(BMD) categorization based on the WHO cut of levels of T-scores and determination
of vitamin D levels were performed. A detailed questionnaire was used to collect
demographic data. RESULTS: Out of 170 participants, 50 (29.4%) were diagnosed as
having osteoporosis, while 68 (40%) were diagnosed with osteopenia. Age was
determined as a risk factor for a decreased BMD in patients with osteopenia (odds
ratio (OR) = 1.1, 95% confidence interval (CI) = (1.0-1.1), p = 0.039) and
osteoporosis (OR = 1.1, CI = 1.0-1.2, p < 0.001). Similarly, oral hypoglycemic
agents (OHA) increased the risk of decreased BMD in osteopenia (OR = 2.6; CI =
1.0-6.7; p = 0.023) as well as osteoporosis, (OR = 3.8; CI = 1.3-10.9; p =
0.013), while vitamin D deficiency increased the risk of osteopenia OR = 3.0; CI
= 1.2-7.2; p = 0.012). Increased BMI decreased the risk of both osteopenia and
osteoporosis (OR = 0.9; CI = 0.9-0.99; p = 0.031 vs. OR = 0.9; CI = 0.80-0.95; p
= 0.003). CONCLUSION: Advanced age, OHA and vitamin D deficiency are determinants
of decreased BMD in Saudi women with type 2 diabetes, while an increased BMI
protects against low BMD.
PMID- 28507625
TI - Surveillance of the Most Prevalent Medical Diseases among Pediatric Age Groups
and Evaluation of the Control Measures Used At Tabuk Hospitals, Saudi Arabia.
AB - BACKGROUND: During the last decades, medical recordings has increased
dramatically leading to more awareness of the diseases commonly affecting
paediatric age groups opening a wide entrance to the prevention of possible
complications and decrease its incidence. AIM: This article aims to assess the
prevalence of the commonly encountered paediatric medical diseases by affected
system among admitted paediatric patients of different age groups in Tabuk and to
identify their burden. METHODS: This is a retrospective research studying disease
pattern according to age, gender, nationality, admission status and length of
stay. RESULTS: Admissions due to respiratory system disorders were the most
common among children under the age of six years (39.7%). Acute gastroenteritis
was the most common disease leading to hospitalisation of children below the age
of three years and cast a financial burden heavily on family and society.
CONCLUSIONS: Respiratory diseases and acute gastroenteritis constitute a
significant burden of childhood illnesses in Tabuk City. Efforts are required to
reduce the impact to achieve the Saudi ministry of health (SMOH) Goal. Even
though Rota vaccine is added to the national Saudi program of vaccination
schedule, other causes should be looked for, and preventive measures are
important as a part of public education.
PMID- 28507626
TI - Follow Up of Value of the Intrarenal Resistivity Indices and Different Renal
Biomarkers for Early Identification of Diabetic Nephropathy in Type 1 Diabetic
Patients.
AB - AIM: To evaluate intrarenal resistivity index (RI) and different biomarkers of
diabetic nephropathy (DN) with clinical signs of DN and its progression over time
as early detection of DN. PATIENTS AND METHODS: This longitudinal study included
48 type 1 diabetic patients who were studied at baseline and after three years. A
blood sample was taken for assessment of glycosylated haemoglobin (HbA1), lipid
profile and a urine sample was taken for assessment of albumin/creatinine ratio,
Neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid binding
protein (L-FABP) and kidney injury molecule-1 (Kim-1) at baseline and after three
years. Forty diabetic patients did renal Doppler at baseline & after three years.
RESULTS: HbA1, waist/hip ratio, albumin/creatinine ratio, lipid profile, NGAL,
KIM-1, L-FABP and resistivity index (RI) were significantly increased in follow
up. Twenty patients (41.7%) showed progression to albuminuria. RI showed a
significant increase in follow-up study. ROC curve showed that RI and NGAL had
the highest sensitivity (100%), followed by L-FABP (90%) and lastly KIM-1 (63.6%)
in the prediction of DN. CONCLUSION: High RI, NGAL, KIM-1 & L-FABP can be
considered as early markers of diabetic nephropathy in type 1 diabetics and are
associated with its progression over time, independent of albuminuria.
PMID- 28507627
TI - Prenatally Diagnosis and Outcome of Fetuses with Cardiac Rhabdomyoma - Single
Centre Experience.
AB - BACKGROUND: Cardiac rhabdomyoma (CRs) are the most common primary tumour of the
heart in infants and children. Usually are multiple and, basing on the location
can cause a haemodynamic disturbance, dysrhythmias or heart failure during the
fetal and early postnatal period. CRs have a natural history of spontaneous
regression and are closely associated with tuberous sclerosis complex (TSC). It
has an association with tuberous sclerosis (TS), and in those, the tumour may
regress and disappear completely, or remain consistent in size. AIM: We aimed to
evaluate the prenatal diagnosis, clinical presentation and outcome of CRs and
their association with TSC in a single centre. The median follow-up period was
three years (range: 6 months - 5 years). MATERIAL AND METHODS: We reviewed
medical records of all fetuses diagnosed prenatally with cardiac rhabdomyoma
covering the period January 2010 to December 2016 which had undergone detailed
ultrasound evaluation at a single centre with limited technical resources.
RESULTS: Twelve fetuses were included in the study; mostly had multiple tumours
and a total of 53 tumours were identified in all patients - the maximum was one
fetus with16 tumours. All patients were diagnosed prenatally by fetal
echocardiography. In two patient's haemodynamic disturbances during the fetal
period was noted and pregnancies have been terminated. After long consultation
termination of pregnancy was chosen by the parents in totally 8 cases. In four
continuing pregnancies during the first year of live tumours regressed. TSC was
diagnosed in all patients during the follow-up. CONCLUSIONS: Cardiac rhabdomyoma
are benign from the cardiovascular standpoint in most affected fetuses. An early
prenatal diagnosis may help for an adequate planning of perinatal monitoring and
treatment with the involvement of a multidisciplinary team. Large tumour size,
the number of tumours and localisation may cause hydrops, and they are
significantly associated with poor neonatal outcome.
PMID- 28507628
TI - Does Vitamin D Deficiency Effect Heart Rate Variability in Low Cardiovascular
Risk Population?
AB - AIM: This study aimed to evaluate the cardiac autonomic dysfunction and the
cardiac arrhythmia risk using heart rate variability parameters in subjects with
vitamin D deficiency and low cardiovascular risk. MATERIAL AND METHODS: One
hundred five consecutive individuals, 54 patients with low vitamin D status and
51 healthy controls were enrolled in this study. The overall cardiac autonomic
tone was quantified by using various heart rate variability parameters included
mean RR interval, mean Heart Rate, mean of standard deviations of intervals for
24 hours (SDNN), standard deviation of averages of intervals (SDANN), mean of
standard deviation of intervals for 5 minutes (SDNNI), root mean square of
difference of successive intervals (rMSSD) and the proportion of intervals
differing more than 50 ms (pNN50) values. The 12-lead ECG was recorded from each
participant, and QT intervals were measured. RESULTS: Baseline demographic
profiles were similar between two groups. The heart rate variability parameters
such as mean RR interval, mean HR, SDNN, SDANN, SDNNI, rMSSD and pNN50 (%) values
were not significantly different in patients with low vitamin D status compared
to control group. The electrocardiography analysis revealed only slight but
significant prolongation of corrected QT (QTc) intervals in the control group.
CONCLUSION: HRV variables were not significantly altered in patients with vitamin
D deficiency in low cardiovascular risk profile group. Further studies evaluating
these findings in other cohorts with high cardiovascular risk are required.
PMID- 28507629
TI - Changes in Kinetic Parameters of Gait in Patients with Supratentorial Unilateral
Stroke in Chronic Period.
AB - AIM: The aim of the study is to evaluate the changes of the kinetic parameters of
gait in patients with supratentorial unilateral stroke in the chronic period
(SUSChP). MATERIAL AND METHODS: The study was conducted with 67 patients with
SUSChP (56 patients included in the experimental group - 32 men and 24 women,
with duration of disease 7.8 +/- 2.0 months, and 11 patients in the control group
- 9 men and 2 women, with duration of disease 7.3 +/- 1.5 months). To evaluate
the changes in the gait were followed cadence of 6 m and 10 m and the speed of
movement which are the most informative kinetic parameters. Patients in the
experimental group were treated with a specialised 10-day KT, which later
continued to be performed as an adapted exercise program at home for one month.
RESULTS: After applying specialised kinesitherapeutic methodology (SKTM), the
highest trend towards improvement in the kinetic parameters of gait was
established after the 1st month with a level of significance during treatment p <
0.001. CONCLUSION: The enclosed SKTM in the experimental group continued later as
an adapted exercise program at home, significantly improving the kinetic
parameters of gait in patients with SUSChP, compared with the usual kinesi
therapeutic methodology applied in the control group.
PMID- 28507630
TI - Relationship between Gait Parameters and Postural Stability in Early and Late
Parkinson's Disease and Visual Feedback-Based Balance Training Effects.
AB - BACKGROUND: Gait disorders or postural instability has been done before. However,
lack of reviews has addressed the relation between gait and postural stability in
Parkinson's disease (PD). AIM: The aim was to evaluate the relation between gait
parameters and postural stability in early and late stages of PD. MATERIALS AND
METHODS: The forty-one idiopathic PD patients were divided into two groups into a
group (A) considered as early PD and group (B) considered as late ambulant PD.
They were evaluated for postural stability by computerised dynamic posturography
(CDP) device and gait analysis using an 8 m-camera Vicon 612 data capturing
system set. RESULTS: There was a statistically significant improvement of
composite equilibrium score, the composite latency of motor response, walking
speed and cadence after treatment as compared to before training (p < 0.05) in
early PD. However, in the late PD, there was a non-significant change of previous
parameters after treatment as compared to before training (p > 0.05). There was a
significant correlation between UPDRS motor part score, walking speed and
composite equilibrium score after training in early PD (p > 0.05). CONCLUSIONS:
Both gait analysis and CDP are important quantitative assessment tools of gait
and posture instability.
PMID- 28507631
TI - Voiding Urosonography with Second-Generation Ultrasound Contrast Agent for
Diagnosis of Vesicoureteric Reflux: First Local Pilot Study.
AB - BACKGROUND: Vesicoureteric reflux (VUR) is an important association of paediatric
urinary tract infection (UTI) found in 30-50% of all children presenting with
first UTI. Contrast-enhanced voiding ultrasonography (ceVUS) has become an
important radiation-free method for VUR detection in children. Its sensitivity in
detecting VUR has greatly improved due to the development of the contrast
specific ultrasound techniques and the introduction of the second-generation
ultrasound contrast agent, superseding the diagnostic accuracy of standard
radiological procedures. AIM: This article aimed to summarise the current
literature and discuss the first local pilot study performed in our institution
on detection of vesicoureteric reflux by contrast-enhanced voiding
ultrasonography with second- generation agent (SonoVue, Bracco, Italy). MATERIAL
AND METHODS: Retrospective review of the first 31 ceVUS (24 girls, 7 boys) was
presented. Age range was 2 months to 18 years (mean = 6.4 +/- 4.9). RESULTS: All
examinations were well tolerated without any adverse incident. VUR was shown in
20 (64.5%) children in 32/62 (51.6) nephroureteral units (NUUs). In 18 NUUs, VUR
was grade II/V, in 11 Grade III/V and in 3 grade IV/V, respectively. Urethra was
shown in 19/31 children and in all boys, without pathological finding. In two
girls spinning top urethra has been detected. Subsequent urodynamic studies
revealed functional bladder problem in both. CONCLUSIONS: Contrast-enhanced
voiding urosonography using intravesical second generation ultrasound contrast
agent could be recommend as a valid alternative diagnostic modality for detecting
vesicoureteral reflux and evaluation of the distal urinary tract in children,
based on its radiation-free, highly efficacious, reliable, and safe
characteristics.
PMID- 28507632
TI - Visfatin versus Flow-Mediated Dilatation as a Marker of Endothelial Dysfunction
in Pediatric Renal Transplant Recipients.
AB - BACKGROUND: Renal transplantation (RTx) is the treatment of choice for paediatric
end-stage renal disease (ESRD). A major cause of morbidity and mortality after
RTx is cardiovascular disease. Independent predictors of cardiovascular events
were shown to constitute an endothelial dysfunction (ED). This study aims to
evaluate Visfatin serum level in comparison to brachial artery flow-mediated
dilatation (FMD) as a marker of endothelial dysfunction in paediatric RTx
recipients. METHODS: Visfatin serum level has been evaluated in 30 patients on
regular hemodialysis (HD), 36 patients post-RTx and 30 controls as a measure for
ED, and has been compared to brachial artery FMD. RESULTS: Visfatin level in
transplant recipients was significantly lower than the hemodialysis group as well
as FMD was better in transplant recipients. In spite of marked improvement of FMD
and marked reduction of visfatin in post-RTx no direct statistical correlation
was found between serum Visfatin level and flow-mediated dilatation. CONCLUSION:
Pediatric RTx recipients show lower serum Visfatin level and better FMD than
those on regular hemodialysis, reflecting less endothelial dysfunction (ED) and
less cardiovascular risk. FMD in kidney transplant recipients tends to be less
than normal subjects while visfatin level of the same group is similar to
controls. Pediatric RTx appears to have a positive impact on the growth
development of children with ESRD.
PMID- 28507633
TI - Deep Vein Thrombosis in Upper Limb in a Weightlifter.
AB - AIM: We report an unusual case of a male weightlifter with upper extremity venous
thrombosis. CASE PRESENTATION: Thrombosis affecting subclavian-axillo-humeral
venous trunk produced by the compression of these veins by the trained muscles of
the shoulder girdle (Paget-Schroetter syndrome) has been reported. During the
study, a renal carcinoma was detected. Renal carcinoma has rarely been associated
with thrombosis in the upper extremities. CONCLUSION: This case shows the
importance of performing a complete study to rule out malignancies in patients
with unusual venous thromboembolism.
PMID- 28507634
TI - Multi-System Complications after Intravenous Cocaine Abuse.
AB - BACKGROUND: Use and abuse of cocaine are associated with numerous adverse
effects, independent of the route of administration. More severe conditions of
poisoning, however, are observed after cocaine intravenous administration. AIM:
We present a case of severe poisoning after violent intravenous injection of
cocaine, but with a good outcome. CASE PRESENTATION: Cocaine was intravenously
(i.v.) administered in 16-years old female patient as a homicide attempt. Shortly
after that, patient experienced series of generalised tonic-clonic seizures, was
highly febrile (40 degrees C), somnolent, agitated, presenting with tachycardia,
tachypnea and with increased blood pressure 150/90 mmHg. Neurologic status,
lumbar puncture and computerised tomography (CT) of the brain were without
remarks. Electroencephalogram (EEG) was characterised with signs of diffuse
encephalopathy, and acid-base analyses resulted in metabolic acidosis. Urine
screening revealed the presence of cocaine and benzodiazepines. The patient
presented with signs of the hepatic lesion, acute renal insufficiency (ARI), and
increased D-dimers resulting from activated fibrinolysis. The patient was
discharged in stable general condition after being hospitalised for 23 days.
CONCLUSION: Intravenous abuse of cocaine results in overdose and serous multi
system complications requiring multidisciplinary diagnostic and intensive
therapeutic approach.
PMID- 28507636
TI - Influence of Number of Implants and Attachment Type on Stress Distribution in
Mandibular Implant-Retained Overdentures: Finite Element Analysis.
AB - AIM: This study aimed to compare the stresses generated by using two or four root
form dental implants supporting mandibular overdentures that were retained with
ball and locator attachments. METHODS: Under ANSYS environment, four 3D finite
element models were prepared. These models simulated complete overdentures
supported by two or four implants with either ball or locator attachments as a
connection mechanism. The models' components were created by CAD/CAM package then
were imported to ANSYS. Load of 100 N was applied at the right premolar/molar
region vertically and at an oblique angle of 110 degrees from lingual direction.
RESULTS: Within the conditions of this research, in all cases, it was found that
cortical and cancellous bone regions were the least to be stressed. Also, the
ball attachment produced higher stresses. CONCLUSION: Caps deformation and
stresses are negligible in cases of using locator attachment in comparison to
ball attachments. This may indicate longer lifetime and less repair/maintenance
operations in implant overdentures retained by locator attachments. Although the
study revealed that bone was insensitive to a number of implants or attachment
type, it may be recommended to use two implants in the canine region than using
four, where the locator attachments were found to be better.
PMID- 28507635
TI - Salivary Immunoglobulin Gene Expression in Patients with Caries.
AB - BACKGROUND: Immunoglobulins mediate the host's humoral immune response are
expressed in saliva. AIM: To quantify the FcalphaR, FcgammaRIIB, and FcalphaMUR
gene expression in the saliva of Mexican patients with caries in mixed and
permanent dentition. SUBJECTS AND METHODS: This was a comparative cross-sectional
study. mRNA was isolated from 200 MUL of saliva following the RNA III Tissue
Fresh-frozen protocol of the MagNA Pure LC Instrument 2.0 (Roche Diagnostics
GmbH, Nederland BV) and the FcalphaR, FcalphaMUR and FcgammaRIIB were quantified
through TaqMan Assays. RESULTS: One hundred individuals, 50 with mixed dentition
and 50 with permanent dentition, were included in the study. Statistically, it
was found a significant difference (p = 0.025) in the IgG (FcgammaRIIB)
expression between the studied groups. CONCLUSION: Although we confirmed the
existence of FcalphaR, FcgammaRIIB and FcalphaMUR gene expression in saliva, only
a significant difference in the expression of FcgammaRIIB between the mixed
dentition and permanent dentition was found.
PMID- 28507637
TI - Factors Influencing Antenatal Haematinics Prescription Behaviour of Physicians in
Calabar, Nigeria.
AB - BACKGROUND: Routine iron and folic acid supplementation in pregnancy have been
proved to be effective in reducing the prevalence and morbidities of anaemia.
However, there is limited data regarding the prescription habits of physician
obstetric care givers. AIM: This study set to investigate the attitudes and
factors which influence the practice among physicians in University of Calabar
Teaching Hospital (UCTH). MATERIAL AND METHODS: A questionnaire based cross
sectional survey was conducted among randomly recruited physician offering
antenatal services between August and September 2015. Systemic sampling was used
to select 70 doctors in the departmental duty roster. Data were presented in
percentages and proportion. Chi-square test was used to test the association
between variables. Statistical significance was set at p < 0.05. RESULTS: The
response rate was 100%. The mean age of the respondents was 30.26 +/- 6.67 years.
All the respondents routinely prescribed haematinics to pregnant women but 34.3%
of them did not prescribe to apparently healthy clients in their first trimester.
Only 30% and 11.4% of them prescribed it in the postnatal and preconception
periods respectively. Brands that contained iron, folate and vitamins as a single
capsule were mostly favoured, and information about brands of drugs was mostly
provided by the pharmaceutical sales representatives. Younger doctors were more
likely to offer haematinics with nutritional counselling compared to older
respondents. However, there was no significant relationship between haematinics
prescription and sex (p = 0.3560), Age (p = 0.839), current professional status
(p = 0.783), and client complaint of side effect of medication (p = 0.23). Oral
medication was mostly utilised. CONCLUSION: Effort to effectively control anaemia
in pregnancy should involve re-orientation of physician obstetric care providers
especially about prenatal and postnatal medication and counselling.
PMID- 28507638
TI - Antibiotic Utilization in Pediatric Hospitalized Patients - A Single Center
Study.
AB - BACKGROUND: Antibiotics are among the most commonly prescribed drugs in
paediatrics. In most cases, antibiotics are started on an empirical basis,
without proof of a bacterial infection, either before the start of therapy or
afterwards. AIM: The main objective of this study was to analyse the consumption
of antibiotics in hospitalised paediatric patients. MATERIAL AND METHODS: This
retrospective study investigated the consumption of antimicrobials in defined
daily doses (DDDs according to the Anatomical Therapeutical Chemical/DDD index)
in Pulmonology, Gastroenterology and Nephrology Departments at Pediatric Clinic
of the tertiary hospital. The data on the consumption of antimicrobials were
collected for five years by using properly designed form. The consumption was
related to days of hospital care. RESULTS: The most utilised antibiotics group in
all three departments Pulmonology, Gastroenterology and Nephrology Departments
were penicillins. Cephalosporins were mostly used in Pulmonology department.
Metronidazole and Chloramphenicol were used in minimal quantities in all three
departments. CONCLUSION: This study demonstrates that surveillance programs on
antibiotic resistance should be established and accompanied by analyses of drug
utilisation data which can aid in the creation of valid cross-national studies on
antibiotic usage and resistance, to motivate improvements in prescribing and
guideline-directed antibiotic prescribing.
PMID- 28507639
TI - Comparative Assessment of Women's Reproductive Health in the Areas Bordering With
the Aral Sea Region.
AB - AIM: We examined 435 women of Aktobe region and 328 women of South Kazakhstan
region, living in areas bordering the Aral Sea region during the study and
comparative assessment of the impact of climatic and anthropogenic factors of
Aral region on the reproductive health of the female population. MATERIAL AND
METHODS: The survey based on the comprehensive clinical-functional and laboratory
studies accounting the regional and environmental ecological factors. Survey
subject was the area of 2 settlements of Aktobe region and 1 settlement of South
Kazakhstan region. RESULTS: In all three areas it was revealed that the examined
women had the later menarche. There is a trend towards younger age for menopause.
The women of South Kazakhstan region often suffer from the pelvic inflammatory
disease. CONCLUSION: Perinatal losses, the case of spontaneous interruption and
stagnant pregnancy in history, which can be repeated, one in three women has in
the zone of ecological disaster.
PMID- 28507640
TI - Histopathological Features of Methotrexate Induced Pulmonary Lesions in
Rheumatoid Arthritis Patients: A Systematic Review of Case Reports.
AB - BACKGROUND: Methotrexate (MTX) is the most commonly used disease-modifying drug
in the treatment of rheumatoid arthritis (RA); however, it causes many side
effects, including pulmonary lesions. In this review, we characterised the
histopathological features of MTX-induced pulmonary lesions in RA patients. AIM:
We carried out an electronic search of the relevant literature published during
the period from 1990 to 2016. We included only the cases with definitive histo
pathological findings caused by MTX therapy. MATERIAL AND METHODS: The total
number of cases is 27. Male: female ratio was 1:3, and ages ranged from 48 to 87
years old, with a mean (SD) = 65.7 (1.0). The cases were originally from Asia
(55%), Europe (41%), and America (4%). The major complications of methotrexate
therapy were lymphoproliferative disorders (42%) followed by interstitial
fibrosis (33), and infections (25%). The incidence of these complications
significantly increases with the duration of MTX treatment (p = 0.044). Among the
infections, the most common causative organism was pneumocystis jiroveci. The
majority of patients who developed infections following methotrexate therapy were
from Europe whereas the majority of those who developed lymphoproliferative
disorders were from Asia (p = 0.003). CONCLUSION: In conclusion, methotrexate
therapy in rheumatoid arthritis patients causes different types pulmonary
complications.
PMID- 28507642
TI - Diagnostic Imaging of Pregnant Women - The Role of Magnetic Resonance Imaging.
AB - BACKGROUND: Presentation of magnetic resonance imaging (MRI) findings in pregnant
women in the Department of Diagnostic Imaging, Institute of Mother and Child,
Warsaw, Poland. MATERIAL/METHODS: Forty-three symptomatic pregnant women
underwent MRI between 9 and 33 weeks of gestation (mean of 23 weeks). Moreover,
we included 2 pregnant women who underwent fetal MRI and had incidental
abnormalities. RESULTS: In 9 cases, we excluded the suspected brain
abnormalities. In 4 cases, we found unremarkable changes in the brain without
clinical significance. One patient was diagnosed with multiple sclerosis, one
with cortical dysplasia, one with pineal hemorrhage and one with a brain tumor.
On abdominal MRI, 2 patients had normal findings, one patient had colon cancer
with a hepatic metastasis, one patient had a hepatic angioma, one patient had an
extraadrenal pheochromocytoma, one patient had an abscess in the iliopsoas
muscle, 9 patients had myomas, two patients had ovarian simple cysts, two
endometrial cysts, three dermoid cysts, one patient had sacrococcygeal teratoma,
one patient had a cystadenofibroma (partial borderline tumor), one patient had an
androgenic ovarian tumor and two patients had hyperreactio luteinalis. One
patient was diagnosed with transient osteoporosis of the hip and one with a
stress fracture of the sacral bone. CONCLUSIONS: Magnetic resonance imaging is
the best imaging modality for pregnant women. Although ultrasonography is the
method of choice, doubtful cases as well as structures that cannot be examined
with ultrasonography can be non-invasively evaluated with MRI.
PMID- 28507641
TI - A case report of Muir-Torre syndrome in a woman with breast cancer and MSI-Low
skin squamous cell carcinoma.
AB - BACKGROUND: The tumor spectrum in the Lynch syndrome is well defined, comprising
an increased risk of developing colonic and extracolonic malignancies. Muir-Torre
syndrome is a variant with a higher risk of skin disease. Patients have been
described carrying mutations in the mismatch repair genes and presenting tumors
with unusual histology or affected organ not part of the Lynch syndrome spectrum.
Hence, the real link between Lynch syndrome, or Muir-Torre syndrome, and these
tumors remains difficult to assess. CASE PRESENTATION: We present the case of a
45-year-old-woman, diagnosed with breast cancer at 39 years of age and skin
squamous cell carcinoma (SCC) at 41 years of age, without personal history of
colorectal cancer. The microsatellite instability analysis performed on the skin
SCC showed a low-level of microsatellite instability (MSI-Low). The
immunohistochemical expression analysis of the four DNA mismatch repair proteins
MLH1, MSH2, MSH6 and PMS2 showed a partial loss of the expression of MSH2 and
MSH6 proteins. Germline deletion was found in MSH2 gene (c.1277-? _1661 + ?del),
exon 8 to 10. Then, at 45 years of age, she presented hyperplastic polyps of the
colon and a sebaceous adenoma. CONCLUSION: Squamous cell carcinomas have been
described in Lynch syndrome and Muir-Torre syndrome in two studies and two case
reports. This new case further supports a possible relationship between Lynch
syndrome and squamous cell carcinoma.
PMID- 28507643
TI - Imaging of Complications After Limb Prostheses Implantation in Children with Bone
Tumors.
AB - BACKGROUND: Tumors of the developmental age are an important problem in clinical
practice. Primary bone tumors constitute 1-1.5% of all tumors, and 7% of all
tumors diagnosed in the developmental age. The aim of the study was to assess the
capabilities of imaging methods in diagnosing complications of limb
endoprostheses in children with osteoarticular tumors. MATERIAL/METHODS: We
included 155 patients with limb endoprostheses, aged 7-26 years. There were 113
patients with knee prostheses, 1 patient with bilateral knee prostheses, 16
patients with shoulder prostheses, 14 patients with hip prostheses, 11 patients
with hip and knee prostheses, and 1 patient with a femoral prosthesis. All
patients underwent plain radiography and an ultrasound study. RESULTS:
Complications were found in 50 patients (32% of all patients). The following
complications were seen - inflammatory changes in soft tissues and bones (12
patients, 7.7%), stump fractures (11 patients, 7%), lack of elongation effect or
shortening of the prosthesis (7 patients, 4.5%), prosthesis fractures (4
patients, 2.5%), crural fractures (4 patients, 2.5%), loosening of the prosthesis
(3 patients, 1.9%), joint dislocation (2 patients, 1.3%), stump and prosthesis
fracture (1 patient, 0.6%) and local recurrence (6 patients, 3.9%). Prostheses
were exchanged for the following reasons - fractures (5 patients, 3.2%),
inflammation (2 patients with 3 exchanges, 1.9%). Local recurrence and
inflammation were confirmed by a biopsy. CONCLUSIONS: Radiography and
ultrasonography are of crucial importance in monitoring patients after
implantation of limb endoprostheses. The findings did not require confirmation in
additional studies: CT and MRI. Suspicion of local recurrence and inflammation
required a biopsy confirmation.
PMID- 28507645
TI - Pharmacists vs employers: A showdown over professional autonomy and patient care?
PMID- 28507646
TI - ?
PMID- 28507644
TI - Autoimmune Pancreatitis.
AB - Autoimmune pancreatitis (AIP) is a rare and underdiagnosed fibrosclerosing
inflammatory variant of chronic pancreatitis. Its true incidence and prevalence
in the general population is still not confirmed despite advances in medicine.
Differentiating it from pancreatic cancer is of paramount importance. In this
imaging review, we highlight the imaging findings of this intriguing entity.
PMID- 28507647
TI - The cost of drugs.
PMID- 28507648
TI - Innovative pharmacy practice: Rick Siemens.
PMID- 28507649
TI - Managing medications during Ramadan fasting.
PMID- 28507650
TI - Part 1: Barriers to the advancement of the pharmacy profession.
PMID- 28507651
TI - Part 2: Roles and expertise needed to move the profession forward and improve
health outcomes.
PMID- 28507652
TI - Practice guidelines for pharmacists: The management of osteoarthritis.
PMID- 28507653
TI - Use of potentially inappropriate medications among ambulatory home-dwelling
elderly patients with dementia: A review of the literature.
AB - BACKGROUND: Older adults with dementia are at high risk for drug-related adverse
outcomes. While much is known about potentially inappropriate medication use in
older adults, its prevalence and characteristics among those with dementia are
not as well elucidated. We conducted a literature review to examine the
prevalence of potentially inappropriate medication use among home-dwelling older
adults with dementia. Our secondary aim was to determine the most frequently
implicated medications and factors associated with potentially inappropriate
medication use. METHODS: MEDLINE, EMBASE, CINAHL, and International
Pharmaceutical Abstracts were searched between 1946 and 2014 for articles that
referenced potentially inappropriate medication use and types of dementia. One
reviewer screened all titles and abstracts from the initial search and full-text
articles after the initial screen for eligibility, then 2 reviewers independently
abstracted data from included studies. RESULTS: Searches yielded 81 articles, of
which 7 met inclusion criteria. Prevalence of potentially inappropriate
medication use varied from 15% to 46.8%. No single drug or drug class was
reported consistently across all studies as the most frequent potentially
inappropriate medication, but anticholinergics and benzodiazepines, drugs that
affect cognition, were among the most common medications or pharmacological
classes listed. DISCUSSION: Older adults with dementia may be particularly
vulnerable to potentially inappropriate medications because of cognitive
impairment from their condition and the greater likelihood of experiencing
adverse events from medications. Given this population's greater susceptibility
to adverse events, more intense medication and patient monitoring may be
warranted, especially among those taking anticholinergics and benzodiazepines, as
these drugs can contribute to cognitive impairment.
PMID- 28507655
TI - How are pharmacists in Ontario adapting to practice change? Results of a
qualitative analysis using Kotter's change management model.
AB - BACKGROUND: The pace of practice change in community pharmacy over the past
decade has been significant, yet there is little evidence documenting
implementation of change in the profession. METHODS: Kotter's change management
model was selected as a theoretical framework for this exploratory qualitative
study. Community pharmacists were interviewed using a semistructured protocol
based on Kotter's model. Data were analyzed and coded using a constant
comparative iterative method aligned with the stages of change management
outlined by Kotter. RESULTS: Twelve community pharmacists were interviewed. Three
key themes emerged: 1) the profession has successfully established the urgency
to, and created a climate conducive for, change; 2) the profession has been less
successful in engaging and enabling the profession to actually implement change;
and 3) legislative changes (for example, expansion of pharmacists' scope of
practice) may have occurred prematurely, prior to other earlier stages of the
change process being consolidated. INTERPRETATION: As noted by most participants,
allowing change is not implementing change: pharmacists reported feeling
underprepared and lacking confidence to actually make change in their practices
and believe that more emphasis on practical, specific implementation tactics is
needed. CONCLUSIONS: Change management is complex and time and resource
intensive. There is a need to provide personalized, detailed, context-specific
implementation strategies to pharmacists to allow them to take full advantage of
expanded scope of practice.
PMID- 28507654
TI - Cost-effectiveness of pharmacist care for managing hypertension in Canada.
AB - BACKGROUND: More than half of all heart disease and stroke are attributable to
hypertension, which is associated with approximately 10% of direct medical costs
globally. Clinical trial evidence has demonstrated that the benefits of
pharmacist intervention, including education, consultation and/or prescribing,
can help to reduce blood pressure; a recent Canadian trial found an 18.3 mmHg
reduction in systolic blood pressure associated with pharmacist care and
prescribing. The objective of this study was to evaluate the economic impact of
such an intervention in a Canadian setting. METHODS: A Markov cost-effectiveness
model was developed to extrapolate potential differences in long-term
cardiovascular and renal disease outcomes, using Framingham risk equations and
other published risk equations. A range of values for systolic blood pressure
reduction was considered (7.6-18.3 mmHg) to reflect the range of potential
interventions and available evidence. The model incorporated health outcomes,
costs and quality of life to estimate an overall incremental cost-effectiveness
ratio. Costs considered included direct medical costs as well as the costs
associated with implementing the pharmacist intervention strategy. RESULTS: For a
systolic blood pressure reduction of 18.3 mmHg, the estimated impact is 0.21
fewer cardiovascular events per person and, discounted at 5% per year, 0.3
additional life-years, 0.4 additional quality-adjusted life-years and $6,364 cost
savings over a lifetime. Thus, the intervention is economically dominant, being
both more effective and cost-saving relative to usual care. DISCUSSION: Across a
range of one-way and probabilistic sensitivity analyses of key parameters and
assumptions, pharmacist intervention remained both effective and cost-saving.
CONCLUSION: Comprehensive pharmacist care of hypertension, including patient
education and prescribing, has the potential to offer both health benefits and
cost savings to Canadians and, as such, has important public health implications.
PMID- 28507656
TI - Development of a Pharmacist REferral Program in a primary cARE clinic (PREPARE):
A prospective cross-sectional study.
AB - BACKGROUND: Increasing demand for ambulatory health care services has led to the
development of primary care multidisciplinary teams that include pharmacists. The
objective of this study was to characterize referrals to a pharmacist in a
primary care clinic (PCC) based in Chilliwack, British Columbia. METHODS: This
prospective cross-sectional study included all patients referred to the PCC
pharmacist over 12 months (May 2015 to April 2016). Data regarding the
source/reason for referral, patient demographics, medical problems/medications
and number/category of identified drug therapy concerns (DTCs) were collected.
RESULTS: A total of 137 referrals were received. Mean age was 60 years and 59%
were female. Twenty patients (15%) did not attend their appointment. Fifty-eight
percent were new clinic patients identified using a Medication Risk Assessment
Questionnaire (MRAQ), 30% were from PCC clinicians and 12% were from community
family physicians. The most common reason for referral was for a medication
review (82%). Median number of medical problems and medications per patient were
7 (interquartile range [IQR] 5) and 11 (IQR 7.5), respectively. A total of 460
DTCs were identified (median 4 per patient, IQR 3.5), of which 34% were
medication without an indication and 28% an untreated indication. DISCUSSION AND
CONCLUSION: The most common source of referrals to a PCC pharmacist was for
medication reviews of new patients using an MRAQ. Most referred patients had
multiple medical problems and polypharmacy, and few were referred for disease
specific management. The number of DTCs per patient was variable and, despite
polypharmacy being commonplace, almost one-third of patients had an untreated
indication.
PMID- 28507658
TI - Canadian Pharmacists Conference 2017 Sponsors.
PMID- 28507657
TI - The essential role of pharmacists in the opioid crisis.
PMID- 28507660
TI - Severe Knee Pain in a 22-year-old Woman After Trauma.
PMID- 28507659
TI - Diagnosis of Arteriovenous Malformation in the Finger.
PMID- 28507661
TI - Bone Marrow Aspirate Concentrate in Combination With Intravenous Iloprost
Increases Bone Healing in Patients With Avascular Necrosis of the Femoral Head: A
Matched Pair Analysis.
AB - With disease progression, avascular necrosis (AVN) of the femoral head may lead
to a collapse of the articular surface. The exact pathophysiology of AVN remains
unclear, although several conditions are known that can result in spontaneous
cell death, leading to a reduction of trabecular bone and the development of AVN.
Hip AVN treatment is stage-dependent in which two main stages of the disease can
be distinguished: pre-collapse (ARCO 0-II) and post-collapse stage (ARCO III-IV,
crescent sign). In the pre-collapse phase, core decompression (CD), with or
without the addition of bone marrow (e.g. bone marrow aspirate concentrate, BMAC)
or bone graft, is a common treatment alternative. In the post-collapse phase, THA
(total hip arthroplasty) must be performed in most of the patients. In addition
to surgical treatment, the intravenous application of Iloprost has been shown to
have a curative potential and analgesic effect. From October 2009 to October
2014, 49 patients with AVN (stages I-III) were treated with core decompression at
our institution. All patients were divided into group A (CD + BMAC) and group B
(CD alone). Of these patients, 20 were included in a matched pair analysis. The
patients were matched to age, gender, ARCO-stage, Kerboul combined necrotic
angle, the cause of AVN, and whether Iloprost-therapy was performed. The Merle
d'Aubigne Score and the Kerboul combined necrotic angle in a-p and lateral
radiographs were evaluated pre- and postoperatively. The primary endpoint was a
total hip arthroplasty. In group A, two patients needed THA while in group B four
patients were treated with THA. In group A, the Merle d'Aubigne Score improved
from 13.5 (pre-operatively) to 15.3 (postoperatively). In group B there was no
difference between the pre- (14.3) and postoperative (14.1) assessment. The mean
of the Kerboul angle showed no difference in both groups compared pre- to
postoperatively (group A: pre-op 212 degrees , postop 220 degrees , group B: pre
op 213, postop 222 degrees ). Regarding radiographic evaluation, the
interobserver variability revealed a moderate agreement between two raters
regarding the pre-(ICC 0.594) and postoperative analysis (ICC 0.604).This study
demonstrates that CD in combination with the application of autologous bone
marrow aspirate concentrate into the femoral head seems to be a safe and
efficient treatment alternative in the early stages of AVN of the femoral head
when compared to CD alone.
PMID- 28507662
TI - Fabrication and nanostructure control of super-hierarchical carbon materials from
heterogeneous bottlebrushes.
AB - Advances in the performances of many modern materials fundamentally depend upon
the exploitation of new micro/nanostructures. Therefore, ingenious design of
hierarchical structures through the mimicking of natural systems is of increasing
importance. Currently, there is an urgent need for creation of multidimensional
carbonaceous structures by integrating a customized hierarchical pore
architecture and hybrid carbon framework. Here we report the pioneering
fabrication of novel super-hierarchical carbons with a unique carbonaceous hybrid
nanotube-interconnected porous network structure by utilizing well-defined carbon
nanotube@polystyrene bottlebrushes as building blocks. Hypercrosslinking of such
heterogeneous core-shell structured building blocks not only allows for
constructing amorphous microporous carbon shells on the surface of graphitic
carbon nanotube cores, but also leads to formation of covalently interconnected
nanoscale networks. Benefiting from such a well-orchestrated structure, these
super-hierarchical carbons exhibit good electrochemical performances. Our
findings may open up a new avenue for fabrication of unique and unusual
functional carbon materials which possess well-orchestrated structural hierarchy
and thus generate valuable breakthroughs in many applications including energy,
adsorption, separation, catalysis and medicine.
PMID- 28507663
TI - Molecular engineering and sequential cosensitization for preventing the "trade
off" effect with photovoltaic enhancement.
AB - In dye-sensitized solar cells (DSSCs), it is essential to use rational molecular
design to obtain promising photosensitizers with well-matched energy levels and
narrow optical band gaps. However, the "trade-off" effect between the
photocurrent and photovoltage is still a challenge. Here we report four
benzoxidazole based D-A-pi-A metal-free organic dyes (WS-66, WS-67, WS-68 and WS
69) with different combinations of pi-spacer units and anchoring-acceptor groups.
Either extending the pi-spacer or enhancing the electron acceptor can efficiently
modulate the molecular energy levels, leading to a red-shift in the absorption
spectra. The optimal dye, WS-69, containing a cyclopentadithiophene (CPDT) spacer
and cyanoacetic acid acceptor, shows the narrowest energy band gap, which
displays a very high photocurrent density of 19.39 mA cm-2, but suffers from a
relatively low photovoltage of 696 mV, along with the so-called deleterious
"trade-off" effect. A cosensitization strategy is further adopted for enhancing
the device performance. Optimization of the dye loading sequence is found to be
capable of simultaneously improving the photocurrent and photovoltage, and
distinctly preventing the "trade-off" effect. The superior cosensitized cell
exhibits an excellent power-conversion efficiency (PCE) of 10.09% under one-sun
irradiation, and 11.12% under 0.3 sun irradiation, which constitutes a great
achievement in that the efficiency of a pure metal-free organic dye with iodine
electrolyte can exceed 11% even under relatively weak light irradiation. In
contrast with the previous cosensitization strategy which mostly focused on
compensation of light-harvesting, we propose a novel cosensitization
architecture, in which the large molecular-sized, high photocurrent dye WS-69
takes charge of broadening the light-harvesting region to generate a high short
circuit current (JSC) while the small molecular-sized, high photovoltage dye WS-5
is responsible for retarding charge recombination to generate a high open-circuit
voltage (VOC). In addition, adsorption amount and photo-stability studies suggest
that the cyano group in the anchoring acceptor is important for the stability
since it is beneficial towards decreasing the LUMO levels and enhancing the
binding of dyes onto TiO2 nanocrystals.
PMID- 28507664
TI - Coevolution and ratiometric behaviour in metal cation-driven dynamic covalent
systems.
AB - Dynamic Covalent Libraries (DCLs) have been used to demonstrate coevolution
behaviour on a molecular level using dynamic covalent molecules such as imines
and hydrazones. Two systems are presented: the first system is based on a
dialdehyde and two diamines in combination with Zn(ii) and Hg(ii) to form a 2 * 2
Constitutional Dynamic Network (CDN) of four complexes of macrocyclic bis-imines.
Whereas the two metal ions, when reacted separately form a complex with each
macrocycle with low selectivity, when applied together, each cation yields
selectively a complex with one of the two macrocycles. Thus, the simultaneous
application of both cations, where one might have expected the formation of four
different complexes, results in the synergistic evolution (co-evolution) towards
a simpler, more selective outcome under agonist amplification. The second system
of 4 components, 2 amines and 2 aldehydes displays metalloselection together with
a correlated evolution in distribution on complexation of Zn(ii) and Cu(i) with
the dynamic ligand constituents and exhibits a dynamic ratiometry process related
to the antagonistic behaviour of a pair of ligand constituents.
PMID- 28507665
TI - Versatile routes for synthesis of diarylamines through acceptorless
dehydrogenative aromatization catalysis over supported gold-palladium bimetallic
nanoparticles.
AB - Diarylamines are an important class of widely utilized chemicals, and development
of diverse procedures for their synthesis is of great importance. Herein, we have
successfully developed novel versatile catalytic procedures for the synthesis of
diarylamines through acceptorless dehydrogenative aromatization. In the presence
of a gold-palladium alloy nanoparticle catalyst (Au-Pd/TiO2), various
symmetrically substituted diarylamines could be synthesized starting from
cyclohexylamines. The observed catalysis of Au-Pd/TiO2 was heterogeneous in
nature and Au-Pd/TiO2 could be reused several times without severe loss of
catalytic performance. This transformation needs no oxidants and generates
molecular hydrogen (three equivalents with respect to cyclohexylamines) and
ammonia as the side products. These features highlight the environmentally benign
nature of the present transformation. Furthermore, in the presence of Au-Pd/TiO2,
various kinds of structurally diverse unsymmetrically substituted diarylamines
could successfully be synthesized starting from various combinations of
substrates such as (i) anilines and cyclohexanones, (ii) cyclohexylamines and
cyclohexanones, and (iii) nitrobenzenes and cyclohexanols. The role of the
catalyst and the reaction pathways were investigated in detail for the
transformation of cyclohexylamines. The catalytic performance was strongly
influenced by the nature of the catalyst. In the presence of a supported gold
nanoparticle catalyst (Au/TiO2), the desired diarylamines were hardly produced.
Although a supported palladium nanoparticle catalyst (Pd/TiO2) gave the desired
diarylamines, the catalytic activity was inferior to that of Au-Pd/TiO2.
Moreover, the activity of Au-Pd/TiO2 was superior to that of a physical mixture
of Au/TiO2 and Pd/TiO2. The present Au-Pd/TiO2-catalyzed transformation of
cyclohexylamines proceeds through complex pathways comprising amine
dehydrogenation, imine disproportionation, and condensation reactions. The amine
dehydrogenation and imine disproportionation reactions are effectively promoted
by palladium (not by gold), and the intrinsic catalytic performance of palladium
is significantly improved by alloying with gold. One possible explanation of the
alloying effect is the formation of electron-poor palladium species that can
effectively promote the beta-H elimination step in the rate-limiting amine
dehydrogenation.
PMID- 28507666
TI - In situ observation of reactive oxygen species forming on oxygen-evolving iridium
surfaces.
AB - Water splitting performed in acidic media relies on the exceptional performance
of iridium-based materials to catalyze the oxygen evolution reaction (OER). In
the present work, we use in situ X-ray photoemission and absorption spectroscopy
to resolve the long-standing debate about surface species present in iridium
based catalysts during the OER. We find that the surface of an initially metallic
iridium model electrode converts into a mixed-valent, conductive iridium oxide
matrix during the OER, which contains OII- and electrophilic OI- species. We
observe a positive correlation between the OI- concentration and the evolved
oxygen, suggesting that these electrophilic oxygen sites may be involved in
catalyzing the OER. We can understand this observation by analogy with
photosystem II; their electrophilicity renders the OI- species active in O-O bond
formation, i.e. the likely potential- and rate-determining step of the OER. The
ability of amorphous iridium oxyhydroxides to easily host such reactive,
electrophilic species can explain their superior performance when compared to
plain iridium metal or crystalline rutile-type IrO2.
PMID- 28507668
TI - Triflimide-catalyzed allylsilane annulations of benzylic alcohols for the
divergent synthesis of indanes and tetralins.
AB - The development of a triflimide-catalyzed annulation of benzylic alcohols with
allylsilanes for the synthesis of indane or tetralin structures is reported. In
this fragment coupling reaction, complexity is built rapidly from readily
available starting materials to yield diverse sets of products with up to three
contiguous stereocenters. Indanes or tetralins can be generated from common
precursors depending on the structure of the allylsilane reagent used. The
concise synthesis of several lignan natural products highlights the utility of
this newly devised methodology.
PMID- 28507667
TI - Photoacoustic probes for real-time tracking of endogenous H2S in living mice.
AB - H2S is a key chemical mediator that exerts a vital role in diverse physiological
and pathological processes. However, in vivo tracking of endogenous H2S
generation still remains difficult due to the lack of reliable analytical
methods. Herein, we present the first example of activatable photoacoustic probes
for real-time imaging of H2S in living mice through the full utilization of the
superiority of photoacoustic imaging modality at fine spatial resolution during
deep tissue penetration. The designed probe can generate high NIR absorption at
780 nm in the presence of H2S, thus producing a strong photoacoustic signal
output in the NIR region. Furthermore, this probe exhibits extremely fast and
highly selective responsiveness, good water-solubility and excellent
biocompatibility. In light of these outstanding features, this probe realizes the
direct photoacoustic trapping of endogenous H2S generation in a HCT116 tumor
bearing mouse model. These preliminary imaging studies show that HCT116 colon
tumors exhibit CBS upregulation activity, resulting in an increased rate of H2S
generation.
PMID- 28507669
TI - Continuous variables logic via coupled automata using a DNAzyme cascade with
feedback.
AB - The concentration of molecules can be changed by chemical reactions and thereby
offer a continuous readout. Yet computer architecture is cast in textbooks in
terms of binary valued, Boolean variables. To enable reactive chemical systems to
compute we show how, using the Cox interpretation of probability theory, one can
transcribe the equations of chemical kinetics as a sequence of coupled logic
gates operating on continuous variables. It is discussed how the distinct
chemical identity of a molecule allows us to create a common language for
chemical kinetics and Boolean logic. Specifically, the logic AND operation is
shown to be equivalent to a bimolecular process. The logic XOR operation
represents chemical processes that take place concurrently. The values of the
rate constants enter the logic scheme as inputs. By designing a reaction scheme
with a feedback we endow the logic gates with a built in memory because their
output then depends on the input and also on the present state of the system.
Technically such a logic machine is an automaton. We report an experimental
realization of three such coupled automata using a DNAzyme multilayer signaling
cascade. A simple model verifies analytically that our experimental scheme
provides an integrator generating a power series that is third order in time. The
model identifies two parameters that govern the kinetics and shows how the
initial concentrations of the substrates are the coefficients in the power
series.
PMID- 28507670
TI - Simultaneous construction of two linkages for the on-surface synthesis of imine
boroxine hybrid covalent organic frameworks.
AB - The orthogonality between the Schiff base reaction and the boronic acid
dehydration reaction is explored during the on-surface synthesis process. By
activating the above two reactions in one-step and employing asymmetrical
substituted monomers and the 3-fold symmetric monomer 1,3,5-tris(4
aminophenyl)benzene (TAPB), highly ordered imine-boroxine hybrid single-layered
covalent organic frameworks (sCOFs) have been successfully constructed on HOPG by
a gas-solid interface reaction method and characterized by scanning tunnelling
microscopy (STM). In particular, the reaction between the meta-substituted
monomer and TAPB generates sCOFB with a windmill structure, which is the first
sCOF with surface chirality so far reported. The demonstration of the one-step
synthesis of multiple linkages to form sCOFs can further enlarge the sCOF family
and expand the design routes for functional 2D organic nanomaterials.
PMID- 28507671
TI - CO/O2 assisted oxidative carbon-carbon and carbon-heteroatom bond cleavage for
the synthesis of oxosulfonates from DMSO and olefins.
AB - Selective carbon-carbon and carbon-heteroatom bond cleavage was achieved in a one
reaction system. With this strategy a novel Pd/Cu-catalyzed aerobic oxidative
oxosulfonation of olefins with DMSO has been developed. Preliminary mechanistic
investigations indicated that CO/O2 assisted the bond cleavage and the leaving
groups from the starting materials were trapped by O2 and underwent a
hydroxylation process.
PMID- 28507672
TI - Mechanism of photocatalytic water oxidation on small TiO2 nanoparticles.
AB - We present the first unconstrained nonadiabatic molecular dynamics (NAMD)
simulations of photocatalytic water oxidation by small hydrated TiO2
nanoparticles using Tully surface hopping and time-dependent density functional
theory. The results indicate that ultrafast electron-proton transfer from
physisorbed water to the photohole initiates the photo-oxidation on the S1
potential energy surface. The new mechanism readily explains the observation of
mobile hydroxyl radicals in recent experiments. Two key driving forces for the
photo-oxidation reaction are identified: localization of the electron-hole pair
and stabilization of the photohole by hydrogen bonding interaction. Our findings
illustrate the scope of recent advances in NAMD methods and emphasize the
importance of explicit simulation of electronic excitations.
PMID- 28507674
TI - Highly specific C-C bond cleavage induced FRET fluorescence for in vivo
biological nitric oxide imaging.
AB - A novel Forster resonance energy transfer (FRET) fluorescence "off-on" system
based on the highly specific, sensitive and effective C-C bond cleavage of
certain dihydropyridine derivatives was reported for real-time quantitative
imaging of nitric oxide (NO). 1,4-Dihydropyridine was synthesized as a novel
linker which could connect customized fluorophores and their corresponding
quenchers. The specific and quantitative response to NO is confirmed using
fluorescence spectrometry with the classical example of fluorescein
isothiocyanate (FITC) and [4'-(N,N'-dimethylamino)phenylazo] benzoyl (DABCYL).
The fluorescence intensity increased linearly with the increase in the amount of
NO. Cells incubated with an exogenous NO donor emitted fluorescence as expected.
A high fluorescence intensity was detected in macrophages which generate NO when
incubated with lipopolysaccharide (LPS). The in vivo imaging shows about an 8
fold contrast between Freund's adjuvant stimulated feet and normal feet in mice
after intravenous injection, which was the first example of in vivo
semiquantitative fluorescence imaging of NO in mammals.
PMID- 28507673
TI - AIEgen-based theranostic system: targeted imaging of cancer cells and adjuvant
amplification of antitumor efficacy of paclitaxel.
AB - Photosensitizers are generally treated as key components for photodynamic
therapy. In contrast, we herein report an aggregation-induced emission luminogen
(AIEgen)-based photosensitizer (TPE-Py-FFGYSA) that can serve as a non-toxic
adjuvant to amplify the antitumor efficacy of paclitaxel, a well-known anticancer
drug, with a synergistic effect of "0 + 1 > 1". Besides the adjuvant function,
TPE-Py-FFGYSA can selectively light up EphA2 protein clusters overexpressed in
cancer cells in a fluorescence turn-on mode, by taking advantage of the specific
YSA peptide (YSAYPDSVPMMS)-EphA2 protein interaction. The simple incorporation of
FFG as a self-assembly-aided unit between AIEgen (TPE-Py) and YSA significantly
enhances the fluorescent signal output of TPE-Py when imaging EphA2 clusters in
live cancer cells. Cytotoxicity and western blot studies reveal that the reactive
oxygen species (ROS) generated by TPE-Py-FFGYSA upon exposure to light do not
kill cancer cells, but instead provide an intracellular oxidative environment to
help paclitaxel have much better efficacy. This study thus not only extends the
application scope of photosensitizers, but also offers a unique theranostic
system with the combination of diagnostic imaging and adjuvant antitumor therapy.
PMID- 28507675
TI - Psychosine variants as antigens for natural killer T cells.
AB - Natural killer T (NKT) cells play a central role in the interface between innate
and adaptive immunity, and alpha-galactosylceramide was recently shown to be an
endogenous antigen for these cells. The source of alpha-galactosylceramide has
not yet been determined; however, in vivo degradation of alpha-galactosylceramide
involves generation of alpha-psychosine (alpha-galactosylsphingosine). Alpha
psychosine stimulates cytokine release from NKT cells and constitutes an
endogenous antigen for these cells. Alpha-psychosine contains a single lipid
chain, while most antigens for NKT cells have two lipid chains, and we have
investigated if other glycolipids with one lipid chain, derived from know
antigens for NKT cells, stimulate cytokine release from NKT cells. Only
psychosine variants derived from the most potent NKT cell antigens cause
stimulation, and this stimulation occurs in vitro as well as in vivo. Truncated
forms of weak antigens for NKT cells are not stimulatory.
PMID- 28507676
TI - Formation mechanism of overlapping grain boundaries in graphene chemical vapor
deposition growth.
AB - The formation of grain boundaries (GBs) in graphene films is both fundamentally
interesting and practically important for many applications. A GB in graphene is
known as a linear defect and is formed during the coalescence of two single
crystalline graphene domains. The covalent binding between domains is broadly
known as the mechanism of GB formation during graphene chemical vapor deposition
(CVD) growth. Here, we demonstrate another GB formation mechanism, where two
graphene domains are connected by weak van der Waals interactions between
overlapping graphene layers. The formation mechanism of the overlapping GBs
(OLGBs) is systematically explored theoretically and the proposed conditions for
forming OLGBs are validated by experimental observations. This discovery leads to
a deep understanding of the mechanism of graphene CVD growth and reveals
potential means for graphene quality control in CVD synthesis.
PMID- 28507677
TI - Pentafluorobenzene end-group as a versatile handle for para fluoro "click"
functionalization of polythiophenes.
AB - A convenient method of introducing pentafluorobenzene (PFB) as a single end-group
in polythiophene derivatives is reported via in situ quenching of the
polymerization. We demonstrate that the PFB-group is a particularly useful end
group due to its ability to undergo fast nucleophilic aromatic substitutions.
Using this molecular handle, we are able to quantitatively tether a variety of
common nucleophiles to the polythiophene backbone. The mild conditions required
for the reaction allows sensitive functional moieties, such as biotin or a cross
linkable trimethoxysilane, to be introduced as end-groups. The high yield enabled
the formation of a diblock rod-coil polymer from equimolar reactants under
transition metal-free conditions at room temperature. We further demonstrate that
water soluble polythiophenes end-capped with PFB can be prepared via the
hydrolysis of an ester precursor, and that such polymers are amenable to
functionalization under aqueous conditions.
PMID- 28507678
TI - Prediction of superconducting iron-bismuth intermetallic compounds at high
pressure.
AB - The synthesis of materials in high-pressure experiments has recently attracted
increasing attention, especially since the discovery of record breaking
superconducting temperatures in the sulfur-hydrogen and other hydrogen-rich
systems. Commonly, the initial precursor in a high pressure experiment contains
constituent elements that are known to form compounds at ambient conditions,
however the discovery of high-pressure phases in systems immiscible under ambient
conditions poses an additional materials design challenge. We performed an
extensive multi component ab initio structural search in the immiscible Fe-Bi
system at high pressure and report on the surprising discovery of two stable
compounds at pressures above ~36 GPa, FeBi2 and FeBi3. According to our
predictions, FeBi2 is a metal at the border of magnetism with a conventional
electron-phonon mediated superconducting transition temperature of Tc = 1.3 K at
40 GPa.
PMID- 28507679
TI - [Ag115S34(SCH2C6H4t Bu)47(dpph)6]: synthesis, crystal structure and NMR
investigations of a soluble silver chalcogenide nanocluster.
AB - With the aim to synthesize soluble cluster molecules, the silver salt of (4-(tert
butyl)phenyl)methanethiol [AgSCH2C6H4t Bu] was applied as a suitable precursor
for the formation of a nanoscale silver sulfide cluster. In the presence of 1,6
(diphenylphosphino)hexane (dpph), the 115 nuclear silver cluster
[Ag115S34(SCH2C6H4t Bu)47(dpph)6] was obtained. The molecular structure of this
compound was elucidated by single crystal X-ray analysis and fully characterized
by spectroscopic techniques. In contrast to most of the previously published
cluster compounds with more than a hundred heavy atoms, this nanoscale inorganic
molecule is soluble in organic solvents, which allowed a comprehensive
investigation in solution by UV-Vis spectroscopy and one- and two-dimensional NMR
spectroscopy including 31P/109Ag-HSQC and DOSY experiments. These are the first
heteronuclear NMR investigations on coinage metal chalcogenides. They give some
first insight into the behavior of nanoscale silver sulfide clusters in solution.
Additionally, molecular weight determinations were performed by 2D analytical
ultracentrifugation and HR-TEM investigations confirm the presence of size
homogeneous nanoparticles present in solution.
PMID- 28507680
TI - An albumin-based tumor-targeted oxaliplatin prodrug with distinctly improved
anticancer activity in vivo.
AB - The design of targeted platinum(iv) prodrugs is a very promising approach to
enhance the low selectivity of platinum(ii) drugs towards cancerous tissue in
order to reduce the impact on healthy tissue and, consequently, the often severe
side-effects. Herein, we report a set of mono-functionalized cis- and oxaliplatin
based platinum(iv) complexes bearing a maleimide moiety, which allows selective
binding to serum albumin in the bloodstream. This leads not only to a prolonged
plasma half-life by avoidance of fast renal clearance, but also to preferential
accumulation of the drug in the tumor tissue due to the EPR-effect. Additionally,
analogous succinimide-functionalized derivatives were prepared to verify the
influence of the maleimide moiety. First experiments showed that all the
maleimide compounds are stable and also possess good albumin-binding properties
in whole serum. Further analytical studies on in vivo samples proved the highly
increased plasma half-life, as well as tumor accumulation of the maleimide
functionalized substances. In vivo antitumor experiments with CT-26-bearing mice
showed that, in contrast to the cisplatin derivatives, the oxaliplatin-based
complexes had exceptionally better activity than the free drug resulting in the
cure of the majority of treated mice. Subsequent analysis suggested that a
distinctly faster reduction as well as reduced tumor accumulation of the
cisplatin derivative might explain the worse performance compared to the
oxaliplatin(iv) complexes. Taken together, a novel lead platinum(iv) complex with
outstanding antitumor activity is presented, which will now be further developed
towards clinical phase I trials.
PMID- 28507682
TI - SABRE hyperpolarisation of vitamin B3 as a function of pH.
AB - In this work we describe how the signal enhancements obtained through the SABRE
process in methanol-d4 solution are significantly affected by pH. Nicotinic acid
(vitamin B3, NA) is used as the agent, and changing pH is shown to modify the
level of polarisation transfer by over an order of magnitude, with significant
improvements being seen in terms of the signal amplitude and relaxation rate at
high pH values. These observations reveal that manipulating pH to improve SABRE
enhancements levels may improve the potential of this method to quantify low
concentrations of analytes in mixtures. 1H NMR spectroscopy results link this
change to the form of the SABRE catalyst, which changes with pH, resulting in
dramatic changes in the magnitude of the ligand exchange rates. The presented
data also uses the fact that the chemical shifts of the nicotinic acids NMR
resonances are affected by pH to establish that hyperpolarised 1H-based pH
mapping with SABRE is possible. Moreover, the strong polarisation transfer field
dependence shown in the amplitudes of the associated higher order longitudinal
terms offers significant opportunities for the rapid detection of hyperpolarised
NA in H2O itself without solvent suppression. 1H and 13C MRI images of
hyperpolarised vitamin B3 in a series of test phantoms are presented that show pH
dependent intensity and contrast. This study therefore establishes that when the
pH sensitivity of NA is combined with the increase in signal gain provided for by
SABRE hyperpolarisation, a versatile pH probe results.
PMID- 28507681
TI - Complementary oligonucleotides regulate induced fit ligand binding in duplexed
aptamers.
AB - Duplexed aptamers (DAs) are engineered by hybridizing an aptamer-complementary
element (ACE, e.g. a DNA oligonucleotide) to an aptamer; to date, ACEs have been
presumed to sequester the aptamer into a non-binding duplex state, in line with a
conformational selection-based model of ligand binding. Here, we uncover that DAs
can actively bind a ligand from the duplex state through an ACE-regulated induced
fit mechanism. Using a widely-studied ATP DNA aptamer and a solution-based
equilibrium assay, DAs were found to exhibit affinities up to 1 000 000-fold
higher than predicted by conformational selection alone, with different ACEs
regulating the level of induced fit binding, as well as the cooperative allostery
of the DA (Hill slope of 1.8 to 0.7). To validate these unexpected findings, we
developed a non-equilibrium surface-based assay that only signals induced fit
binding, and corroborated the results from the solution-based assay. Our findings
indicate that ACEs regulate ATP DA ligand binding dynamics, opening new avenues
for the study and design of ligand-responsive nucleic acids.
PMID- 28507683
TI - Supramolecular assembly of platinum-containing polyhedral oligomeric
silsesquioxanes: an interplay of intermolecular interactions and a correlation
between structural modifications and morphological transformations.
AB - A series of alkynylplatinum(ii) terpyridine complexes functionalized with
polyhedral oligomeric silsesquioxane (POSS) moieties has been demonstrated to
exhibit drastic color changes and give various distinctive nanostructures with
interesting multi-stage morphological transformations from spheres to nanoplates
in response to solvent conditions through the interplay of various intermolecular
interactions, including hydrophilic-hydrophilic, hydrophobic-hydrophobic, Pt...Pt
and pi-pi stacking interactions. These supramolecular architectures can be
systematically modified and controlled through the molecular design and the
variation of solvent compositions. In particular, drastic changes in color in
response to solvent polarity were observed through the incorporation of the
charged moieties, representing a new class of potential candidates for functional
materials with sensing or imaging capabilities. This class of complexes has been
studied by 1H NMR spectroscopy, electron microscopy, UV-vis absorption and
emission spectroscopy.
PMID- 28507684
TI - Synthesis and reactivity of a ruthenocene-type complex bearing an aromatic pi
ligand with the heaviest group 14 element.
AB - An anionic ruthenocene derived from a dilithioplumbole complex was prepared. In
the complex, the plumbole ligand coordinates a ruthenium atom in an eta5-fashion,
similar to the cyclopentadienyl ligand in ferrocene. The ruthenocene that has the
aromatic pi-ligand with the heaviest group 14 element reacted with electrophiles
to afford the plumbole complexes wherein the plumbole ligands show deviation from
planarity, in contrast to the planar plumbole ring in the anionic ruthenocene.
The bent angles of the plumbole ligands are dependent on the substituents on the
lead atoms. Cyclic voltammetry measurements revealed that the plumbole complexes
are oxidized more easily than the corresponding stannole complexes.
PMID- 28507685
TI - Design of a thermally controlled sequence of triazolinedione-based click and
transclick reactions.
AB - The reaction of triazolinediones (TADs) and indoles is of particular interest for
polymer chemistry applications, as it is a very fast and irreversible additive
free process at room temperature, but can be turned into a dynamic covalent bond
forming process at elevated temperatures, giving a reliable bond exchange or
'transclick' reaction. In this paper, we report an in-depth study aimed at
controlling the TAD-indole reversible click reactions through rational design of
modified indole reaction partners. This has resulted in the identification of a
novel class of easily accessible indole derivatives that give dynamic TAD-adduct
formation at significantly lower temperatures. We further demonstrate that these
new substrates can be used to design a directed cascade of click reactions of a
functionalized TAD moiety from an initial indole reaction partner to a second
indole, and finally to an irreversible reaction partner. This controlled sequence
of click and transclick reactions of a single TAD reagent between three different
substrates has been demonstrated both on small molecule and macromolecular level,
and the factors that control the reversibility profiles have been rationalized
and guided by mechanistic considerations supported by theoretical calculations.
PMID- 28507687
TI - A mild catalytic system for radical conjugate addition of nitrogen heterocycles.
AB - The direct addition of pyridine and diazine units to electron-poor alkenes has
been achieved via a redox radical mechanism that is enabled by limiting the
effective concentration of the hydrogen-atom source. The described method is
tolerant of acidic functional groups and is generally applicable to the union of
a wide range of Michael acceptors and 6-membered heterocyclic halides.
PMID- 28507686
TI - Gas confinement in compartmentalized coordination polymers for highly selective
sorption.
AB - Discrimination between different gases is an essential aspect for industrial and
environmental applications involving sensing and separation. Several classes of
porous materials have been used in this context, including zeolites and more
recently MOFs. However, to reach high selectivities for the separation of gas
mixtures is a challenging task that often requires the understanding of the
specific interactions established between the porous framework and the gases.
Here we propose an approach to obtain an enhanced selectivity based on the use of
compartmentalized coordination polymers, named CCP-1 and CCP-2, which are
crystalline materials comprising isolated discrete cavities. These
compartmentalized materials are excellent candidates for the selective separation
of CO2 from methane and nitrogen. A complete understanding of the sorption
process is accomplished with the use of complementary experimental techniques
including X-ray diffraction, adsorption studies, inelastic- and quasi-elastic
neutron scattering, magnetic measurements and molecular dynamics calculations.
PMID- 28507688
TI - Donor-acceptor stacking arrangements in bulk and thin-film high-mobility
conjugated polymers characterized using molecular modelling and MAS and surface
enhanced solid-state NMR spectroscopy.
AB - Conjugated polymers show promising properties as cheap, sustainable and solution
processable semiconductors. A key challenge in the development of these materials
is to determine the polymer chain structure, conformation and packing in both the
bulk polymer and in thin films typically used in devices. However, many
characterisation techniques are unable to provide atomic-level structural
information owing to the presence of disorder. Here, we use molecular modelling,
magic-angle spinning (MAS) and dynamic nuclear polarisation surface-enhanced NMR
spectroscopy (DNP SENS) to characterise the polymer backbone group conformations
and packing arrangement in the high-mobility donor-acceptor copolymer
diketopyrrolo-pyrrole-dithienylthieno[3,2-b]thiophene (DPP-DTT). Using
conventional 1H and 13C solid-state MAS NMR coupled with density functional
theory calculations and molecular dynamics simulations, we find that the bulk
polymer adopts a highly planar backbone conformation with a laterally-shifted
donor-on-acceptor stacking arrangement. DNP SENS enables acquisition of 13C NMR
data for polymer films, where sensitivity is limiting owing to small sample
volumes. The DNP signal enhancement enables a two-dimensional 1H-13C HETCOR
spectrum to be recorded for a drop-cast polymer film, and a 13C CPMAS NMR
spectrum to be recorded for a spin-coated thin-film with a thickness of only 400
nm. The results show that the same planar backbone structure and intermolecular
stacking arrangement is preserved in the films following solution processing and
annealing, thereby rationalizing the favourable device properties of DPP-DTT, and
providing a protocol for the study of other thin film materials.
PMID- 28507689
TI - Tuning the separation and coupling of corannulene trianion-radicals through
sizable alkali metal belts.
AB - The first heterobimetallic sandwich-type aggregate formed by bowl-shaped
corannulene trianion-radicals, C20H103-, has been synthesized using mixed-metal
reduction of C20H10. The product was crystallographically characterized to reveal
the self-assembly of [Cs+//(C20H103-)/4K+/(C20H103-)//Cs+], in which two triply
charged corannulene decks encapsulate a rectangle of four potassium ions (the
K...K separations are 4.212(4) and 5.185(4) A), with the exterior concave bowl
cavities being selectively filled by one cesium ion each. In order to provide
insights into the geometrical features and electronic structure of this novel
mixed-metal organometallic self-assembly, an in-depth theoretical investigation
has been carried out. Specifically, the influence of internal metal binding on
the geometry and magnetic coupling of C20H103- radicals is investigated for Group
1 metals. This study reveals that replacement of the sandwiched potassium ions
with larger (Cs) and smaller (Li) ions allows variation of the size of the
encapsulated metal belts, and thus enables tuning of the coupling of C20H103-
radicals.
PMID- 28507690
TI - A bifunctional cerium phosphate catalyst for chemoselective acetalization.
AB - Acid-base solid catalysts synthesized with structurally controlled uniform active
sites can lead to unique catalysis. In this study, a CePO4 catalyst was
synthesized using a hydrothermal method and found to exhibit high catalytic
performance for the chemoselective acetalization of 5-hydroxymethylfurfural with
alcohols, in sharp contrast to other homogeneous and heterogeneous acid and/or
base catalysts. In the presence of CePO4, various combinations of carbonyl
compounds and alcohols are efficiently converted into the corresponding acetal
derivatives in good to excellent yields. Mechanistic studies show that CePO4 most
likely acts as a bifunctional catalyst through the interaction of uniform Lewis
acid and weak base sites with 5-hydroxymethylfurfural and alcohol molecules,
respectively, which results in high catalytic performance.
PMID- 28507691
TI - Mechanism of resonant electron emission from the deprotonated GFP chromophore and
its biomimetics.
AB - The Green Fluorescent Protein (GFP), which is widely used in bioimaging, is known
to undergo light-induced redox transformations. Electron transfer is thought to
occur resonantly through excited states of its chromophore; however, a detailed
understanding of the electron gateway states of the chromophore is still missing.
Here, we use photoelectron spectroscopy and high-level quantum chemistry
calculations to show that following UV excitation, the ultrafast electron
dynamics in the chromophore anion proceeds via an excited shape resonance
strongly coupled to the open continuum. The impact of this state is found across
the entire 355-315 nm excitation range, from above the first bound-bound
transition to below the opening of higher-lying continua. By disentangling the
electron dynamics in the photodetachment channels, we provide an important
reference for the adiabatic position of the electron gateway state, which is
located at 348 nm, and discover the source of the curiously large widths of the
photoelectron spectra that have been reported in the literature. By introducing
chemical modifications to the GFP chromophore, we show that the detachment
threshold and the position of the gateway state, and hence the underlying excited
state dynamics, can be changed systematically. This enables a fine tuning of the
intrinsic electron emission properties of the GFP chromophore and has significant
implications for its function, suggesting that the biomimetic GFP chromophores
are more stable to photooxidation.
PMID- 28507692
TI - High-level ab initio potential energy surface and dynamics of the F- + CH3I SN2
and proton-transfer reactions.
AB - Bimolecular nucleophilic substitution (SN2) and proton transfer are fundamental
processes in chemistry and F- + CH3I is an important prototype of these
reactions. Here we develop the first full-dimensional ab initio analytical
potential energy surface (PES) for the F- + CH3I system using a permutationally
invariant fit of high-level composite energies obtained with the combination of
the explicitly-correlated CCSD(T)-F12b method, the aug-cc-pVTZ basis, core
electron correlation effects, and a relativistic effective core potential for
iodine. The PES accurately describes the SN2 channel producing I- + CH3F via
Walden-inversion, front-side attack, and double-inversion pathways as well as the
proton-transfer channel leading to HF + CH2I-. The relative energies of the
stationary points on the PES agree well with the new explicitly-correlated all
electron CCSD(T)-F12b/QZ-quality benchmark values. Quasiclassical trajectory
computations on the PES show that the proton transfer becomes significant at high
collision energies and double-inversion as well as front-side attack trajectories
can occur. The computed broad angular distributions and hot internal energy
distributions indicate the dominance of indirect mechanisms at lower collision
energies, which is confirmed by analyzing the integration time and leaving group
velocity distributions. Comparison with available crossed-beam experiments shows
usually good agreement.
PMID- 28507694
TI - A convergent synthesis of 1,3,4-oxadiazoles from acyl hydrazides under
semiaqueous conditions.
AB - The 1,3,4-oxadiazole is an aromatic heterocycle valued for its low-lipophilicity
in drug development. Substituents at the 2- and/or 5-positions can modulate the
heterocycle's electronic and hydrogen bond-accepting capability, while exploiting
its use as a carbonyl bioisostere. A new approach to 1,3,4-oxadiazoles is
described wherein alpha-bromo nitroalkanes are coupled to acyl hydrazides to
deliver the 2,5-disubstituted oxadiazole directly, avoiding a 1,2-diacyl
hydrazide intermediate. Access to new building blocks of oxadiazole-substituted
secondary amines is improved by leveraging chiral alpha-bromo nitroalkane or
amino acid hydrazide substrates. The non-dehydrative conditions for oxadiazole
synthesis are particularly notable, in contrast to alternatives reliant on highly
oxophilic reagents to effect cyclization of unsymmetrical 1,2-diacyl hydrazides.
The mild conditions are punctuated by the straightforward removal of co-products
by a standard aqueous wash.
PMID- 28507693
TI - Fluorocarbene, fluoroolefin, and fluorocarbyne complexes of Rh.
AB - The manuscript reports the synthesis, characterization, and analysis of
electronic structure in a series of complexes of small perfluorocarbon ligands
with the (PNP)Rh fragment (where PNP is a diarylamido/bis(phosphine) pincer
ligand). Reactions of (PNP)Rh(TBE) as the source of (PNP)Rh with CHF3 and C2HF5
produced perfluoroalkylidene complexes (PNP)Rh 0000000000000000000000000000000000
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0000000000000000000000000000000000 CF2 and (PNP)RhC(F)(CF3). (PNP)RhCF2 could
also be obtained via the reaction of (PNP)Rh(TBE) with Me3SiCF3/CsF, with an
admixture of (PNP)Rh(C2F4), where TBE = tert-butylethylene. Abstraction of
fluoride from these neutral (PNP)RhC x F y complexes was successful, although
only abstraction from (PNP)RhCF2 allowed unambiguous identification of the Rh
product, [(PNP)Rh 0000000000000000000000000000000000
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0000000000000000000000000000000000 CF]+. DFT computational studies allowed
comparison of relative energies of (PNP)Rh(C2F4) and [(PNP)Rh(C2F3)]+ isomers as
well as comparisons between the electronic structure of the CF2, C2F4, and CF+
complexes and their hydrocarbon analogues.
PMID- 28507695
TI - ANI-1: an extensible neural network potential with DFT accuracy at force field
computational cost.
AB - Deep learning is revolutionizing many areas of science and technology, especially
image, text, and speech recognition. In this paper, we demonstrate how a deep
neural network (NN) trained on quantum mechanical (QM) DFT calculations can learn
an accurate and transferable potential for organic molecules. We introduce ANAKIN
ME (Accurate NeurAl networK engINe for Molecular Energies) or ANI for short. ANI
is a new method designed with the intent of developing transferable neural
network potentials that utilize a highly-modified version of the Behler and
Parrinello symmetry functions to build single-atom atomic environment vectors
(AEV) as a molecular representation. AEVs provide the ability to train neural
networks to data that spans both configurational and conformational space, a feat
not previously accomplished on this scale. We utilized ANI to build a potential
called ANI-1, which was trained on a subset of the GDB databases with up to 8
heavy atoms in order to predict total energies for organic molecules containing
four atom types: H, C, N, and O. To obtain an accelerated but physically relevant
sampling of molecular potential surfaces, we also proposed a Normal Mode Sampling
(NMS) method for generating molecular conformations. Through a series of case
studies, we show that ANI-1 is chemically accurate compared to reference DFT
calculations on much larger molecular systems (up to 54 atoms) than those
included in the training data set.
PMID- 28507696
TI - Highly chemoselective ruthenium(ii)-catalyzed direct arylation of cyclic and N,N
dialkyl benzamides with aryl silanes.
AB - The ruthenium(ii)-catalyzed oxidative cross-coupling of C(sp2)-H bonds with
organosilanes has been accomplished for the first time. This novel protocol
enlists challenging cyclic and N,N-dialkyl benzamides as weakly-coordinating
substrates to achieve highly regioselective C(sp2)-H arylation as a proof-of
concept, taking advantage of the attractive features of organosilanes as coupling
partners. This innovative method is characterized by very high chemoselectivity,
installing halide functional groups (I, Br, Cl) that are incompatible with Ru(ii)
carboxylate systems employing halides as cross-coupling partners, while obviating
the need for sensitive organometallic reagents and cryogenic temperatures typical
to the classic directed-ortho-metallation (DoM) techniques, employing benzamides
to afford bioactive structural motifs.
PMID- 28507698
TI - Formicamycins, antibacterial polyketides produced by Streptomyces formicae
isolated from African Tetraponera plant-ants.
AB - We report a new Streptomyces species named S. formicae that was isolated from the
African fungus-growing plant-ant Tetraponera penzigi and show that it produces
novel pentacyclic polyketides that are active against MRSA and VRE. The chemical
scaffold of these compounds, which we have called the formicamycins, is similar
to the fasamycins identified from the heterologous expression of clones isolated
from environmental DNA, but has significant differences that allow the scaffold
to be decorated with up to four halogen atoms. We report the structures and
bioactivities of 16 new molecules and show, using CRISPR/Cas9 genome editing,
that biosynthesis of these compounds is encoded by a single type 2 polyketide
synthase biosynthetic gene cluster in the S. formicae genome. Our work has
identified the first antibiotic from the Tetraponera system and highlights the
benefits of exploring unusual ecological niches for new actinomycete strains and
novel natural products.
PMID- 28507697
TI - Regulating the active species of Ni(OH)2 using CeO2: 3D CeO2/Ni(OH)2/carbon foam
as an efficient electrode for the oxygen evolution reaction.
AB - Three dimensional (3D) N, O and S doped carbon foam (NOSCF) is prepared as a
substrate for in situ vertically grown Ni(OH)2 nanosheets. As designed
Ni(OH)2/NOSCF possesses strong electrostatic interactions with OH- ions due to
many C 0000000000000000000000000000000000 0000000000000000000000000000000000
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existing in NOSCF, which can facilitate the formation of crucial NiOOH
intermediates during the OER process. CeO2 nanoparticles (NPs) of ~3.3 nm in size
are decorated on Ni(OH)2 nanosheets to design a highly efficient
CeO2/Ni(OH)2/NOSCF electrocatalyst for the oxygen evolution reaction (OER). The
CeO2 NP decorated Ni(OH)2/NOSCF not only exhibits a remarkably improved OER
performance with an onset potential of 240 mV, outperforming most reported non
noble metal based OER electrocatalysts, but also possesses a small Tafel slope of
57 mV dec-1 and excellent stability under different overpotentials. The
synergistic effect of producing more active species of NiIII/IV and accelerating
the charge transfer for Ni(OH)2/NOSCF by the introduction of CeO2 NPs is also
investigated. These results demonstrate the possibility of designing energy
efficient OER catalysts with the assistance of earth abundant CeO2-based
catalysts.
PMID- 28507699
TI - Polylysine-grafted Au144 nanoclusters: birth and growth of a healthy surface
plasmon-resonance-like band.
AB - Poly(amino acid)-coated gold nanoparticles hold promise in biomedical
applications, particularly because they combine the unique physicochemical
properties of the gold core, excellent biocompatibility, and easy
functionalization of the poly(amino acid)-capping shell. Here we report a novel
method for the preparation of robust hybrid core-shell nanosystems consisting of
a Au144 cluster and a densely grafted polylysine layer. Linear polylysine chains
were grown by direct N-carboxyanhydride (NCA) polymerization onto ligands capping
the gold nanocluster. The density of the polylysine chains and the thickness of
the polymer layer strongly depend on the amount and concentration of the NCA
monomer and the initiator. The optical spectra of the so-obtained core-shell
nanosystems show a strong surface plasmon resonance (SPR)-like band at 531 nm. In
fact, despite maintenance of the gold cluster size and the absence of
interparticle aggregation, the polylysine-capped clusters behave as if they have
a diameter nearly 4 times larger. To the best of our knowledge, this is the first
observation of the growth of a fully developed, very stable SPR-like band for a
gold nanocluster of such dimensions. The robust polylysine protective shell makes
the nanoparticles very stable under conditions of chemical etching, in the
presence of glutathione, and at different pH values, without gold core
deshielding or alteration of the SPR-like band. This polymerization method can
conceivably be extended to prepare core-shell nanosystems based on other mono- or
co-poly(amino acids).
PMID- 28507700
TI - Stepwise observation and quantification and mixed matrix membrane separation of
CO2 within a hydroxy-decorated porous host.
AB - The identification of preferred binding domains within a host structure provides
important insights into the function of materials. State-of-the-art reports
mostly focus on crystallographic studies of empty and single component guest
loaded host structures to determine the location of guests. However, measurements
of material properties (e.g., adsorption and breakthrough of substrates) are
usually performed for a wide range of pressure (guest coverage) and/or using
multi-component gas mixtures. Here we report the development of a multifunctional
gas dosing system for use in X-ray powder diffraction studies on Beamline I11 at
Diamond Light Source. This facility is fully automated and enables in situ
crystallographic studies of host structures under (i) unlimited target gas
loadings and (ii) loading of multi-component gas mixtures. A proof-of-concept
study was conducted on a hydroxyl-decorated porous material MFM-300(VIII) under
(i) five different CO2 pressures covering the isotherm range and (ii) the loading
of equimolar mixtures of CO2/N2. The study has successfully captured the
structural dynamics underpinning CO2 uptake as a function of surface coverage.
Moreover, MFM-300(VIII) was incorporated in a mixed matrix membrane (MMM) with
PIM-1 in order to evaluate the CO2/N2 separation potential of this material. Gas
permeation measurements on the MMM show a great improvement over the bare PIM-1
polymer for CO2/N2 separation based on the ideal selectivity.
PMID- 28507701
TI - Peptide-templated noble metal catalysts: syntheses and applications.
AB - Noble metal catalysts have been widely used in many applications because of their
high activity and selectivity. However, a controllable preparation of noble metal
catalysts still remains as a significant challenge. To overcome this challenge,
peptide templates can play a critical role in the controllable syntheses of
catalysts owing to their flexible binding with specific metallic surfaces and
self-assembly characteristics. By employing peptide templates, the size, shape,
facet, structure, and composition of obtained catalysts can all be specifically
controlled under the mild synthesis conditions. In addition, catalysts with
spherical, nanofiber, and nanofilm structures can all be produced by associating
with the self-assembly characteristics of peptide templates. Furthermore, the
peptide-templated noble metal catalysts also reveal significantly enhanced
catalytic behaviours compared with conventional catalysts because the electron
conductivity, metal dispersion, and reactive site exposure can all be improved.
In this review, we summarize the research progresses in the syntheses of peptide
templated noble metal catalysts. The applications of the peptide-templated
catalysts in organic reactions, photocatalysis, and electrocatalysis are
discussed, and the relationship between structure and activity of these catalysts
are addressed. Future opportunities, including new catalytic materials designed
by using biological principles, are indicated to achieve selective, eco-friendly,
and energy neutral synthesis approaches.
PMID- 28507702
TI - Plasmon-induced charge separation: chemistry and wide applications.
AB - Recent development of nanoplasmonics has stimulated chemists to utilize plasmonic
nanomaterials for efficient and distinctive photochemical applications, and
physicists to boldly go inside the "wet" chemistry world. The discovery of
plasmon-induced charge separation (PICS) has even accelerated these trends. On
the other hand, some confusion is found in discussions about PICS. In this
perspective, we focus on differences between PICS and some other phenomena such
as co-catalysis effect and plasmonic nanoantenna effect. In addition, materials
and nanostructures suitable for PICS are shown, and characteristics and features
unique to PICS are documented. Although it is well known that PICS has been
applied to photovoltaics and photocatalysis, here light is shed on other
applications that take better advantage of PICS, such as chemical sensing and
biosensing, various photochromisms, photoswitchable functionalities and nanoscale
photofabrication.
PMID- 28507703
TI - Advanced electroanalytical chemistry at nanoelectrodes.
AB - Nanoelectrodes, with dimensions below 100 nm, have the advantages of high
sensitivity and high spatial resolution. These electrodes have attracted
increasing attention in various fields such as single cell analysis, single
molecule detection, single particle characterization and high-resolution imaging.
The rapid growth of novel nanoelectrodes and nanoelectrochemical methods brings
enormous new opportunities in the field. In this perspective, we discuss the
challenges, advances, and opportunities for nanoelectrode fabrication, real-time
characterizations and high-performance electrochemical instrumentation.
PMID- 28507704
TI - Elucidation of salicylate attachment in celesticetin biosynthesis opens the door
to create a library of more efficient hybrid lincosamide antibiotics.
AB - Lincosamides, which are produced by streptomycetes, compose a small but
clinically important class of antibiotics. The recent elucidation of the
condensation and post-condensation biosynthetic steps of the lincosamides
lincomycin and celesticetin revealed several unexpected reaction mechanisms.
Here, we prepared recombinant proteins involved in the celesticetin biosynthetic
pathway and used them for in vitro assays that were monitored by LC-MS. Our
results elucidate the last biosynthetic step of celesticetin: the attachment of
salicylic acid is catalyzed by the Ccb2 acyl-CoA ligase and the Ccb1
acyltransferase. Ccb1 belongs to the WS/DGAT protein family and, in contrast to
the characterized members of the family, has unusual substrate specificity. To
the best of our knowledge, Ccb1 is the first protein in this family that
transfers a benzoyl derivative-CoA conjugate and is the first WS/DGAT protein
involved in the biosynthesis of secondary metabolites. Furthermore, we exploited
the relaxed substrate specificities of Ccb1 and Ccb2, as well as three additional
upstream post-condensation biosynthetic proteins in the celesticetin pathway, and
combined the lincomycin and the celesticetin biosynthetic pathways in vitro. In
this way, we prepared a library of 150 novel hybrid lincosamides, including two
unnatural chimeras of lincomycin and celesticetin, which were shown to have
antibacterial properties more pronounced than clinically used lincomycin. These
achievements may be considered a case study in applying knowledge about
biosynthetic machinery to assemble a large number of compounds from originally a
small group of natural products without the need for chemical synthesis.
PMID- 28507705
TI - Acid- and Au(i)-mediated synthesis of hexathymidine-DNA-heterocycle chimeras, an
efficient entry to DNA-encoded libraries inspired by drug structures.
AB - Libraries of DNA-tagged compounds are a validated screening technology for drug
discovery. They are synthesized through combinatorial iterations of alternated
coding and preparative synthesis steps. Thus, large chemical space can be
accessed for target-based screening. However, the need to preserve the
functionality of the DNA tag severely restricts the choice of chemical methods
for library synthesis. Acidic organocatalysts, transition metals, and oxidants
furnish diverse drug-like structures from simple starting materials, but cause
loss of genetic information by depurination. A hexathymidine oligonucleotide,
called "hexT" allows the chemist utilizing these classes of catalysts to access a
potentially broad variety of structures in the initial step of library synthesis.
We exploited its catalyst tolerance to efficiently synthesize diverse substituted
beta-carbolines, pyrazolines, and pyrazoles from readily available starting
materials as hexT conjugates by acid- and Au(i)-catalysis, respectively. The hexT
conjugates were ligated to coding DNA sequences yielding encoded screening
libraries inspired by drug structures.
PMID- 28507706
TI - pH- and ligand-induced release of loads from DNA-acrylamide hydrogel
microcapsules.
AB - Herein, a method to construct stimuli-responsive DNA-acrylamide-based hydrogel
microcapsules has been presented. This method involves the use of polyacrylamide
chains modified with predesigned nucleic acid hairpin units and optionally single
strand tethers that provide the required hybridization and recognition functions
to yield substrate-loaded stimuli-responsive hydrogel-based microcapsules. The
synthesis of the microcapsules involves the loading of CaCO3 microparticles with
the respective load substrates and the functionalization of the CaCO3 template
particles with nucleic acid promoter units. In the presence of the hairpin
modified acrylamide chains, the promoter units induce the hybridization chain
reaction (HCR), which leads to the formation of a hydrogel coating, which, after
the dissociation of the CaCO3 cores, yields substrate-loaded stimuli-responsive
hydrogel microcapsules. One of the microcapsule systems includes, in the hairpin
modified acrylamide constructs, and in the subsequent HCR-generated hydrogel
shells, the caged sequences of anti-ATP or anti-cocaine aptamers. In the presence
of ATP or cocaine, the duplex-caged aptamer sequences are separated via the
formation of ATP- or cocaine-aptamer complexes, which results in the partial
separation of the microcapsules and the release of the loads. The second type of
microcapsule is cooperatively stabilized by bridges generated by HCR and pH
sensitive duplex units. Under acidic conditions, the pH-sensitive bridges
dissociate via the formation of i-motif structures, which results in an increase
in the fluidity of the microcapsule shells and the release of the loads.
Preliminary studies indicate that ATP- or pH-responsive microcapsules loaded with
the anticancer drug, doxorubicin, have a selective cytotoxic effect on MDA-MB-231
cancer cells.
PMID- 28507708
TI - Manganese-catalyzed allylation via sequential C-H and C-C/C-Het bond activation.
AB - Manganese-catalyzed sequential C-H and C-C/C-Het bond activation to synthesize
allylic alcohols, allylated arenes, functionalized cyclopentenes and skipped
dienes is reported. This protocol can be readily scaled up and various coupling
partners are applied in manganese catalysis for the first time. Moreover,
manganese-catalyzed alkenyl C(sp2)-H activation is also shown. Complimentary to
the standard solution-based protocols, these reactions also proceed efficiently
under neat conditions, which is unprecedented for abundant metal catalyzed C-H
activation reactions.
PMID- 28507707
TI - Nanophase-separated Ni3Nb as an automobile exhaust catalyst.
AB - Catalytic remediation of automobile exhaust has relied on precious metals (PMs)
including platinum (Pt). Herein, we report that an intermetallic phase of Ni and
niobium (Nb) (i.e., Ni3Nb) exhibits a significantly higher activity than that of
Pt for the remediation of the most toxic gas in exhaust (i.e., nitrogen monoxide
(NO)) in the presence of carbon monoxide (CO). When subjected to the exhaust
remediation atmosphere, Ni3Nb spontaneously evolves into a catalytically active
nanophase-separated structure consisting of filamentous Ni networks (thickness <
10 nm) that are incorporated in a niobium oxide matrix (i.e., NbO x (x < 5/2)).
The exposure of the filamentous Ni promotes NO dissociation, CO oxidation and N2
generation, and the NbO x matrix absorbs excessive nitrogen adatoms to retain the
active Ni0 sites at the metal/oxide interface. Furthermore, the NbO x matrix
immobilizes the filamentous Ni at elevated temperatures to produce long-term and
stable catalytic performance over hundreds of hours.
PMID- 28507709
TI - First total synthesis of concavine.
AB - The synthesis of the unusual alkaloid concavine, isolated from Clitocybe concava
(Basidiomycetae), has been accomplished. The synthetic route features regio- and
stereoselective manipulation of polycyclic imide intermediates via enolate
substitution and Grignard addition, along with a key bridge-forming step
involving a new method for sulfenylative radical cyclisation. The NMR data for
synthetic concavine demonstrate that the original data reported for the natural
product refer to the derived acetic acid salt, probably formed as an artefact of
isolation or purification.
PMID- 28507711
TI - Interfacial engineering of renewable metal organic framework derived honeycomb
like nanoporous aluminum hydroxide with tunable porosity.
AB - Novel honeycomb-like mesoporous aluminum hydroxide (pATH) was synthesized via a
facile one-step reaction by employing ZIF-8 as a template. This self-decomposing
template was removed automatically under acidic conditions without the need for
any tedious or hazardous procedures. Meanwhile, the pore size of pATH was easily
modulated by tuning the dimensions of the ZIF-8 polyhedrons. Of paramount
importance was the fact that the dissolved ZIF-8 in solution was regenerated upon
deprotonation of the ligand under mild alkali conditions, and was reused in the
preparation of pATH, thus forming a delicate synthesis cycle. The renewable
template conferred cost-effective and sustainable features to the as-synthesized
product. As a proof-of-concept application, the fascinating nanoporous structure
enabled pATH to load more phosphorous-containing flame retardant and endowed
better interaction with epoxy resin over that of commercial aluminum hydroxide.
The limiting oxygen index, UL-94 vertical burning test and cone calorimeter test
showed that the results of epoxy with the modified pATH rivalled those of epoxy
with two times the loading amount of the commercial counterpart, while the former
presented better mechanical properties. The proposed "amorphous replica method"
used in this work will advance the potential for launching a vast area of
research and technology development for the preparation of porous metal
hydroxides for use in practical applications.
PMID- 28507710
TI - Semiconducting polymer dots with bright narrow-band emission at 800 nm for
biological applications.
AB - The development of near-infrared (NIR) fluorescent probes is critical for in vivo
exploration of the fundamental and complex processes in living systems by
noninvasive fluorescence imaging techniques. Semiconducting polymer dots (Pdots)
are emerging as important probes that exhibit several advantages, such as high
brightness and biocompatibility. However, NIR-emitting Pdots are very rare,
particularly at the center (~800 nm) of the first optical window of biological
tissues (between 650 nm and 950 nm). In this paper, we describe the synthesis of
a semiconducting polymer with bright and narrow-band emission at 800 nm. The
polymer was designed by incorporating a NIR porphyrin unit into a conjugated
backbone; the polymer used a cascade energy transfer to produce the signal. The
resulting Pdots possessed a narrow emission bandwidth (FWHM ~ 23 nm) and good
fluorescence quantum yield (QY = 8%), which is high for a near-IR emitter. The
Pdots were bioconjugated with streptavidin for specific labeling of cellular
targets, yielding higher staining index when compared with commercial NIR probes,
such as PE-Cy7. Moreover, the NIR polymer was combined with a long-wavelength
absorbing polymer to make bright Pdots (QY = 15%) for in vivo noninvasive
imaging. These NIR Pdots with surface PEGylation led to high-contrast imaging of
lymph nodes and tumors in a mouse model. This work highlights the great potential
of the NIR Pdots for cellular and in vivo imaging applications.
PMID- 28507712
TI - Redox non-innocence permits catalytic nitrene carbonylation by (dadi)Ti
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adamantyl).
AB - Application of the diamide, diimine {-CHN(1,2-C6H4)N(2,6-iPr2-C6H3)}2m ((dadi) m
) ligand to titanium provided adducts (dadi)TiL x (1-L x ; L x = THF, PMe2Ph,
(CNMe)2), which possess the redox formulation [(dadi)4-]Ti(iv)L x , and 22 pie-
(4n + 2). Related complexes containing titanium-ligand multiple bonds, (dadi)TiX
(2 X; X = O, NAd), exhibit a different dadi redox state, [(dadi)2-]Ti(iv)X,
consistent with 20 pie- (4n). The Redox Non-Innocence (RNI) displayed by dadi m
impedes binding by CO, and permits catalytic conversion of AdN3 + CO to AdNCO +
N2. Kinetics measurements support carbonylation of 2 NAd as the rate determining
step. Structural and computational evidence for the observed RNI is provided.
PMID- 28507713
TI - White-light emission from discrete heterometallic lanthanide-directed self
assembled complexes in solution.
AB - White-light-emitting materials have attracted significant interest in recent
years due to their potential applications in solid-state lighting and flat-panel
displays. Design of such materials is challenging and often relies on the use of
multiple fluorophores despite the fact that single component systems yield
materials with enhanced stability and reproducibility. Herein, we have developed
a white-light-emitting system based on the formation of discrete lanthanide-based
self-assembled complexes using a newly-designed ligand. We demonstrate that fine
tuning of the lanthanide ions molar ratio in the self-assemblies combined with
the intrinsic blue fluorescence of the ligand allows for the successful emission
of pure white light with CIE coordinates of (0.33, 0.34).
PMID- 28507714
TI - Targeting the tumour microenvironment with an enzyme-responsive drug delivery
system for the efficient therapy of breast and pancreatic cancers.
AB - The development of novel therapeutic strategies allowing the destruction of
tumour cells while sparing healthy tissues is one of the main challenges of
cancer chemotherapy. Here, we report on the design and antitumour activity of a
low-molecular-weight drug delivery system programmed for the selective release of
the potent monomethylauristatin E in the tumour microenvironment of solid
tumours. After intravenous administration, this compound binds covalently to
plasmatic albumin through Michael addition, thereby enabling its passive
accumulation in tumours where extracellular beta-glucuronidase initiates the
selective release of the drug. This targeting device produces outstanding
therapeutic efficacy on orthotopic triple-negative mammary and pancreatic tumours
in mice (50% and 33% of mice with the respective tumours cured), leading to
impressive reduction or even disappearance of tumours without inducing side
effects.
PMID- 28507715
TI - A quantitative mechanistic PK/PD model directly connects Btk target engagement
and in vivo efficacy.
AB - Correlating target engagement with in vivo drug activity remains a central
challenge in efforts to improve the efficiency of drug discovery. Previously we
described a mechanistic pharmacokinetic-pharmacodynamic (PK/PD) model that used
drug-target binding kinetics to successfully predict the in vivo efficacy of
antibacterial compounds in models of Pseudomonas aeruginosa and Staphylococcus
aureus infection. In the present work we extend this model to quantitatively
correlate the engagement of Bruton's tyrosine kinase (Btk) by the covalent
inhibitor CC-292 with the ability of this compound to reduce ankle swelling in an
animal model of arthritis. The modeling studies include the rate of Btk turnover
and reveal the vulnerability of Btk to engagement by CC-292.
PMID- 28507716
TI - Chemistry in nanoconfined water.
AB - Nanoconfined liquids have extremely different properties from the bulk, which
profoundly affects chemical reactions taking place in nanosolvation. Here, we
present extensive ab initio simulations of a vast set of chemical reactions
within a water lamella that is nanoconfined by mineral surfaces, which might be
relevant to prebiotic peptide formation in aqueous environments. Our results
disclose a rich interplay of distinct effects, from steric factors typical of
reactions occurring in small spaces to a charge-stabilization effect in
nanoconfined water at extreme conditions similar to that observed in bulk water
when changing from extreme to ambient conditions. These effects are found to
modify significantly not only the energetics but also the mechanisms of reactions
happening in nanoconfined water in comparison to the corresponding bulk regime.
PMID- 28507717
TI - Dynamic, structural and thermodynamic basis of insulin-like growth factor 1
kinase allostery mediated by activation loop phosphorylation.
AB - Despite the importance of kinases' catalytic activity regulation in cell
signaling, detailed mechanisms underlying their activity regulation are poorly
understood. Herein, using insulin-like growth factor 1 receptor kinase (IGF-1RK)
as a model, the mechanisms of kinase regulation by its activation loop (A-loop)
phosphorylation were investigated through molecular dynamics (MD) and alchemical
free energy simulations. Analyses of the simulation results and free energy
landscapes determined for the entire catalytic cycle of the kinase revealed that
A-loop phosphorylation affects each step in the IGF-1RK catalytic cycle,
including conformational change, substrate binding/product release and catalytic
phosphoryl transfer. Specifically, the conformational equilibrium of the kinase
is shifted by 13.2 kcal mol-1 to favor the active conformation after A-loop
phosphorylation, which increases substrate binding affinity of the activated
kinase. This free energy shift is achieved primarily via destabilization of the
inactive conformation. The free energy of the catalytic reaction is also changed
by 3.3 kcal mol-1 after the phosphorylation and in the end, facilitates product
release. Analyses of MD simulations showed that A-loop phosphorylation produces
these energetic effects by perturbing the side chain interactions around each A
loop tyrosine. These interaction changes are propagated to the remainder of the
kinase to modify the orientations and dynamics of the alphaC-helix and A-loop,
and together yield the observed free energy changes. Since many protein kinases
share similar interactions identified in this work, the mechanisms of kinase
allostery and catalysis unraveled here can be applicable to them.
PMID- 28507718
TI - Copper-catalyzed direct alkylation of heteroarenes.
AB - An efficient and broadly applicable process is reported for the direct alkylation
of C-H bonds in heteroarenes, privileged scaffolds in many areas of science. This
reaction is based on the copper-catalyzed addition of alkyl radicals generated
from activated secondary and tertiary alkyl bromides to a wide range of arenes,
including furans, thiophenes, pyrroles, and their benzo-fused derivatives, as
well as coumarins and quinolinones.
PMID- 28507719
TI - Broad substrate tolerance of tubulin tyrosine ligase enables one-step site
specific enzymatic protein labeling.
AB - The broad substrate tolerance of tubulin tyrosine ligase is the basic rationale
behind its wide applicability for chemoenzymatic protein functionalization. In
this context, we report that the wild-type enzyme enables ligation of various
unnatural amino acids that are substantially bigger than and structurally
unrelated to the natural substrate, tyrosine, without the need for extensive
protein engineering. This unusual substrate flexibility is due to the fact that
the enzyme's catalytic pocket forms an extended cavity during ligation, as
confirmed by docking experiments and all-atom molecular dynamics simulations.
This feature enabled one-step C-terminal biotinylation and fluorescent coumarin
labeling of various functional proteins as demonstrated with ubiquitin, an
antigen binding nanobody, and the apoptosis marker Annexin V. Its broad substrate
tolerance establishes tubulin tyrosine ligase as a powerful tool for in vitro
enzyme-mediated protein modification with single functional amino acids in a
specific structural context.
PMID- 28507720
TI - In vivo imaging of leucine aminopeptidase activity in drug-induced liver injury
and liver cancer via a near-infrared fluorescent probe.
AB - The liver, a main detoxification organ, has evolved a complex enzymatic system to
respond to multiple pathological conditions, in which leucine aminopeptidase
(LAP) has been reported to participate in detoxifying cisplatin in hepatoma cells
and contribute to the intrinsic drug resistance. In vivo imaging of LAP activity
in liver disease models is thus helpful to further understand the function of LAP
in detoxification and medicine, but such an imaging approach is still lacking.
Herein, we develop a selective and sensitive near-infrared fluorescent probe
(HCAL) for this purpose. Using the probe, combined with confocal fluorescence
imaging, we disclose the upregulations of LAP in acetaminophen-induced liver
injury and tumor-bearing mice models. Supplementary acetylcysteine can suppress
this upregulation, revealing that the LAP increase may be connected with a
deficiency in biothiols. Moreover, HCAL has been used to image LAP in hepatoma
cells, tumor tissues and xenograft tumor mice models successfully. These results
demonstrate that HCAL may be a promising tool for studying the function of LAP in
LAP-associated liver diseases.
PMID- 28507721
TI - Mo6+ activated multimetal oxygen-evolving catalysts.
AB - Water splitting is key to electrically-powered chemical fuel synthesis, but the
slow kinetics of the oxygen evolution reaction (OER) hinder the wider promotion
of such technology. Several first-row (3d) transition metal-based catalysts have
been developed for the OER; however, these catalysts still require operating
voltages that lie well above the fundamental thermodynamic potential. Here, we
report high-valence metal molybdenum (Mo6+) modulated 3d metal (oxy)hydroxides.
The obtained multimetal FeCoMo based OER catalysts require an overpotential of
277 mV to reach the current density of 10 mA cm-2 on the glassy carbon electrode,
and there was no evidence of degradation for about 40 hours of stability testing.
The catalysts stay in their amorphous phases, potentially with atomically
homogenous metal distribution. The in situ X-ray adsorption analysis
unambiguously reveals the tuned electronic structures of the 3d metals owing to
Mo6+, further demonstrating the modification effect of a high-valence metal for
designing highly-efficient OER catalysts.
PMID- 28507722
TI - Novel bright-emission small-molecule NIR-II fluorophores for in vivo tumor
imaging and image-guided surgery.
AB - Though high brightness and biocompatible small NIR-II dyes are highly desirable
in clinical or translational cancer research, their fluorescent cores are
relatively limited and their synthetic processes are somewhat complicated.
Herein, we have explored the design and synthesis of novel NIR-II fluorescent
materials (H1) without tedious chromatographic isolation with improved
fluorescence performance (QY ~ 2%) by introducing 2-amino 9,9-dialkyl-substituted
fluorene as a donor into the backbone. Several types of water-soluble and
biocompatible NIR-II probes: SXH, SDH, and H1 NPs were constructed via different
chemical strategies based on H1, and then their potential to be used in in vivo
tumor imaging and image-guided surgery in the NIR-II region was explored. High
levels of uptake were obtained for both passive and active tumor targeting probes
SXH and SDH. Furthermore, high resolution imaging of blood vessels on tumors and
the whole body of living mice using H1 NPs for the first time has demonstrated
precise NIR-II image-guided sentinel lymph node (SLN) surgery.
PMID- 28507723
TI - p-Doping of graphene in hybrid materials with 3,10-diazapicenium dications.
AB - N,N'-Didodecyl-substituted 3,10-diazapicenium salts featuring bromide and
hexafluorophosphate counterions have been designed as novel dopants to realize
individualized graphene sheets in a series of cutting edge experiments and to
intrinsically stabilize them via p-doping. Importantly, electrochemical studies
revealed two consecutive irreversible one-electron reductions of the N,N'
didodecyl-substituted 3,10-diazapicenium salts to yield the corresponding radical
cation and neutral quinoidal species. Formation of both species was accompanied
by characteristic changes in the absorption spectra. The 3,10-diazapicenium
bromide was found to be a potent dopant to produce hybrid materials with
exfoliated graphene. Microscopy based on AFM and TEM imaging and spectroscopy
based on Raman probing corroborated that, upon drying, the hybrid material
consists of few layer (5-8 layers) turbostratic graphene sheets that are p-doped.
Our findings identify the newly synthesized N,N'-dialkylated 3,10-diazapicenium
salts as highly promising candidates for the fabrication of functional graphene
materials with tailored properties.
PMID- 28507724
TI - Deep learning and 3D-DESI imaging reveal the hidden metabolic heterogeneity of
cancer.
AB - Visual inspection of tumour tissues does not reveal the complex metabolic changes
that differentiate cancer and its sub-types from healthy tissues. Mass
spectrometry imaging, which quantifies the underlying chemistry, represents a
powerful tool for the molecular exploration of tumour tissues. A 3-dimensional
topological description of the chemical properties of the tumour permits the
formulation of hypotheses about the biological composition and interactions and
the possible causes of its heterogeneous structure. The large amount of
information contained in such datasets requires powerful tools for its analysis,
visualisation and interpretation. Linear methods for unsupervised dimensionality
reduction, such as PCA, are inadequate to capture the complex non-linear
relationships present in these data. For this reason, a deep unsupervised neural
network based technique, parametric t-SNE, is adopted to map a 3D-DESI-MS dataset
from a human colorectal adenocarcinoma biopsy onto a 2-dimensional manifold. This
technique allows the identification of clusters not visible with linear methods.
The unsupervised clustering of the tumour tissue results in the identification of
sub-regions characterised by the abundance of identified metabolites, making
possible the formulation of hypotheses to account for their significance and the
underlying biological heterogeneity in the tumour.
PMID- 28507725
TI - Metal-free C-H alkylation of heteroarenes with alkyltrifluoroborates: a general
protocol for 1 degrees , 2 degrees and 3 degrees alkylation.
AB - A photoredox-catalyzed C-H functionalization of heteroarenes using a variety of
primary, secondary, and tertiary alkyltrifluoroborates is reported. Using
Fukuzumi's organophotocatalyst and a mild oxidant, conditions amenable for
functionalizing complex heteroaromatics are described, providing a valuable tool
for late-stage derivatization. The reported method addresses the three major
limitations of previously reported photoredox-mediated Minisci reactions: (1) use
of superstoichiometric amounts of a radical precursor, (2) capricious
regioselectivity, and (3) incorporation of expensive photocatalysts.
Additionally, a number of unprecedented, complex alkyl radicals are used, thereby
increasing the chemical space accessible to Minisci chemistry. To showcase the
application in late-stage functionalization, quinine and camptothecin analogues
were synthesized. Finally, NMR studies were conducted to provide a
rationalization for the heteroaryl activation that permits the use of a single
equivalent of radical precursor and also leads to enhanced regioselectivity.
Thus, by 1H and 13C NMR a distinct heteroaryl species was observed in the
presence of acid catalyst and BF3.
PMID- 28507727
TI - Correlation between hemoglobin A1c and serum lipid profile in Afghani patients
with type 2 diabetes: hemoglobin A1c prognosticates dyslipidemia.
AB - BACKGROUND: Patients with type 2 diabetes (T2DM) have an increased prevalence of
dyslipidemia, which contributes to their high risk of cardiovascular diseases
(CVDs). This study is an attempt to determine the correlation between hemoglobin
A1c (HbA1c) and serum lipid profile and to evaluate the importance of HbA1c as an
indicator of dyslipidemia in Afghani patients with T2DM. METHODS: A total of 401
Afghani patients with T2DM (men, 175; women, 226; mean age, 51.29 years) were
included in this study. The whole blood and sera were analyzed for fasting blood
sugar (FBS), HbA1c, total cholesterol (TC), triglycerides (TGs), high-density
lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C).
Dyslipidemia was defined according to the National Cholesterol Education Program
Adult Treatment Panel III (NCEP ATP III) guidelines. Diabetes was defined as per
American Diabetes Association criteria. The correlation of FBS, HbA1c with lipid
ratios and individual lipid indexes were analyzed. The statistical analysis was
done by SPSS statistical package version 16.0. RESULTS: The mean age +/- standard
deviation of male and female patients were 51.71 +/- 11.70 and 50.97 +/- 10.23
years respectively. There was a significant positive correlation between HbA1c,
TC, TG, LDL-C and LDL-C/HDL-C ratio. The correlation between HbA1c and HDL-C was
negative and was statistically nonsignificant. Furthermore, HbA1c was found to be
a predictor of hypercholesterolemia, LDL-C and TG via a linear regression
analysis. Patients with HbA1c value greater than 7.0% had significantly higher
value of cholesterol, LDL-C, and LDL-C/HDL-C ratio compared with patients with an
HbA1c value up to 7.0%. CONCLUSIONS: Apart from a reliable glycemic index, HbA1c
can also be used as a predictor of dyslipidemia and thus early diagnosis of
dyslipidemia can be used as a preventive measure for the development of CVD in
patients with T2DM.
PMID- 28507726
TI - Adapting tissue-engineered in vitro CNS models for high-throughput study of
neurodegeneration.
AB - Neurodegenerative conditions remain difficult to treat, with the continuing
failure to see therapeutic research successfully advance to clinical trials. One
of the obstacles that must be overcome is to develop enhanced models of disease.
Tissue engineering techniques enable us to create organised artificial central
nervous system tissue that has the potential to improve the drug development
process. This study presents a replicable model of neurodegenerative pathology
through the use of engineered neural tissue co-cultures that can incorporate
cells from various sources and allow degeneration and protection of neurons to be
observed easily and measured, following exposure to neurotoxic compounds -
okadaic acid and 1-methyl-4-phenylpyridinium. Furthermore, the technology has
been miniaturised through development of a mould with 6 mm length that recreates
the advantageous features of engineered neural tissue co-cultures at a scale
suitable for commercial research and development. Integration of human-derived
induced pluripotent stem cells aids more accurate modelling of human diseases,
creating new possibilities for engineered neural tissue co-cultures and their use
in drug screening.
PMID- 28507728
TI - Therapeutic plasmapheresis for hypertriglyceridemia-associated acute
pancreatitis: case series and review of the literature.
AB - BACKGROUND: Severe hypertriglyceridemia (HTG) is the third leading cause of acute
pancreatitis (AP) in the United States. The current standard of care includes
management of HTG using pharmacological therapy. More recently, plasmapheresis
has been proposed as a therapeutic tool for decreasing triglyceride (TG) levels,
especially in critically ill patients. Few studies are available to ascertain
overall benefits of plasmapheresis over traditional management. OBJECTIVE: To
analyze the outcomes of patients treated with plasmapheresis for severe HTG
associated pancreatitis. METHODS: We conducted a retrospective chart review of
three patients with severe HTG- associated (TGs greater than 1000 mg/dl; 11.29
mmol/l) AP at the Methodist University Hospital. All the patients underwent
plasmapheresis as part of their treatment. RESULTS: The average TG level before
plasmapheresis was 3532 mg/dl (range: 2524-4562 mg/dl; 39.9 mmol/l; range: 28.5
51.6 mmol/l). All patients made a full recovery, with a significant improvement
in TG levels after plasmapheresis. The mean number of sessions was 1.3 (range 1
2), and mean TG level after plasmapheresis was 1051 mg/dl (range: 509-1771 mg/dl;
11.9 mmol/l; range: 5.8-20 mmol/l). After the first session, the average
reduction of TG level was 2481 mg/dl (range 753-3750 mg/dl; 28 mmol/l; range: 8.5
42.4 mmol/l) or approximately 70%. None of the patients developed complications
related to plasmapheresis. CONCLUSIONS: Plasmapheresis can be an effective and
rapid treatment option in patients with severe HTG and complications. However,
further research, including randomized controlled studies, is necessary.
PMID- 28507729
TI - Difference in clinical presentation between women and men in incident primary
Sjogren's syndrome.
AB - BACKGROUND: A more severe disease phenotype has been reported in men compared to
women in several rheumatic diseases. However, studies have not conclusively
established sex-related clinical features in primary Sjogren's syndrome (pSS). In
this study, we therefore investigated the clinical presentation of pSS in women
and men at diagnosis. METHODS: Incident, treatment naive patients (n = 199)
during a 5-year period in a specified area were prospectively included and
examined for items of classification criteria for pSS as well as extraglandular
manifestations (EGM). Serum was sampled at the time of diagnosis and anti
Ro52/SSA levels were measured by ELISA. Replication of significant findings was
confirmed in an independent cohort of pSS patients (n = 377), and meta-analysis
was performed. RESULTS: An increased frequency of extraglandular manifestations
in men was observed and replicated (p = 0.05, p = 0.0003, and pmeta = 0.002).
This related to pulmonary involvement, vasculitis, and lymphadenopathy being more
common in men, for whom a lower age at diagnosis was observed in the exploratory
cohort. Additionally, SSA-positive male patients had significantly higher levels
of anti-Ro52 levels than their female counterparts in sera available for analysis
(p = 0.02). CONCLUSIONS: Our analysis of two independent cohorts of incident pSS
demonstrates that the presence and number of EGM are significantly more frequent
among men with pSS than women at diagnosis. Importantly, around half of the male
patients presented with more than one EGM at diagnosis, supporting the conclusion
that pSS in men represents a more severe form of disease, regardless of the lower
risk for men to develop pSS.
PMID- 28507732
TI - Conquering the deadly stroke: Perspective on a surgeon's odyssey.
AB - *An odyssey of a Japanese surgeon, who survived a life-threatening hemorrhagic
stroke.*Self-motivation and adherence to work ethics displayed by the surgeon to
return to work is admirable.*Passion is a detrimental factor that enables
surgeons to overcome a roadblock to their career.
PMID- 28507731
TI - Patient engagement with surgical site infection prevention: an expert panel
perspective.
AB - Despite remarkable developments in the use of surgical techniques, ergonomic
advancements in the operating room, and implementation of bundles, surgical site
infections (SSIs) remain a substantial burden, associated with increased
morbidity, mortality and healthcare costs. National and international
recommendations to prevent SSIs have been published, including recent guidelines
by the World Health Organization, but implementation into clinical practice
remains an unresolved issue. SSI improvement programs require an integrative
approach with measures taken during the pre-, intra- and postoperative care from
the numerous stakeholders involved. The current SSI prevention strategies have
focused mainly on the role of healthcare workers (HCWs) and procedure related
risk factors. The importance and influence of patient participation is becoming
an increasingly important concept and advocated as a means to improve patient
safety. Novel interventions supporting an active participative role within SSI
prevention programs have not been assessed. Empowering patients with information
they require to engage in the process of SSI prevention could play a major role
for the implementation of recommendations. Based on available scientific
evidence, a panel of experts evaluated options for patient involvement in order
to provide pragmatic recommendations for pre-, intra- and postoperative
activities for the prevention of SSIs. Recommendations were based on existing
guidelines and expert opinion. As a result, 9 recommendations for the surgical
patient are presented here, including a practice brief in the form of a patient
information leaflet. HCWs can use this information to educate patients and allow
patient engagement.
PMID- 28507733
TI - Assessment of postgraduate skin lesion education among Iowa family physicians.
AB - BACKGROUND: Family medicine physicians play a pivotal role in the prevention and
early detection of skin cancer. Our objective was to evaluate how family
physicians believe their postgraduate training in skin cancer screening and
prevention has prepared them for independent practice and to assess the need for
enhanced skin lesion teaching in a family medicine residency setting. METHODS: A
descriptive, cross-sectional survey investigating provider demographics,
confidence in providing dermatological care, residency training, current medical
practice, and skin cancer prevention beliefs was mailed to all family medicine
physicians in the state of Iowa as listed in the Iowa Academy of Family
Physicians annual directory in 2006 (N = 1069). RESULTS: A total of 575 family
medicine physicians completed the survey for an overall response rate of 53.8%.
Overall, family medicine physicians reported feeling confident in their ability
to diagnose skin lesions (83.2%), differentiate between benign and malignant
lesions (85.3%), and perform a biopsy of a lesion (94.3%). Only 65% of surveyed
physicians felt that their residency program adequately trained them in
diagnosing skin lesions and 65.7% of physicians agree that they could have
benefited from additional training on skin lesions during residency training.
Nearly 90% of clinicians surveyed believe that skin cancer screenings are the
standard of care; however, only 51.8% perform skin cancer screening examinations
during adult health maintenance visits more than 75% of the time. The primary
reason listed by respondents who said they do not routinely perform skin cancer
screenings was inadequate time (68.2%). CONCLUSION: Family medicine physicians in
the state of Iowa are confident in evaluating skin lesions. However, they
reported a need for additional enhanced, targeted skin lesion education in family
medicine residency training programs. Physicians believe that skin cancer
screening examination is the standard of care, but find that inadequate time
increasingly hinders skin cancer screening during routine health maintenance
examinations.
PMID- 28507734
TI - Adverse effect profile comparison of pain regimens with and without intravenous
acetaminophen in total hip and knee arthroplasty patients.
AB - BACKGROUND: The use of adjunct, non-opioid agents is integral for pain control
following total hip and knee arthroplasty. Literature comparing safety profiles
of intravenous acetaminophen versus opioids is lacking. OBJECTIVE: To determine
whether there is a difference in frequency and type of adverse effects between
intravenous acetaminophen-treated and non-intravenous acetaminophen-treated
patients. Primary safety endpoints included any adverse effect noted in the
electronic medical record post-surgically. Secondary endpoints included changes
in laboratory values, vital signs, and pain scores. METHODS: This is a
retrospective, matched, cohort study with data collected from electronic medical
records. Adverse effects were collected from progress notes, nursing notes, and
post-operative notes. Mean pain score was measured by the 11-point visual analog
scale over a 72-h period. RESULTS: A total of 609 patients who underwent a total
hip or knee replacement were included. In all, 406 patients were treated with
intravenous acetaminophen, and 203 patients received medication management
without intravenous acetaminophen. More patients treated with intravenous
acetaminophen experienced an adverse effect compared to patients who did not
receive intravenous acetaminophen (91.63% versus 84.73%; p = 0.012). Mean
cumulative acetaminophen exposure was similar in the intravenous acetaminophen
group (7704.89 +/- 2558.6 versus 7260.1 +/- 3016.09 mg; p = 0.07). Mean opioid
use was similar in the intravenous acetaminophen group as compared to the non
intravenous acetaminophen group (209.61 +/- 555.09 versus 163.89 +/- 232.44 mg; p
= 0.152). Significantly higher mean pain scores were found in the intravenous
acetaminophen group during the 72-h post-surgery period as compared with non
intravenous acetaminophen-treated patients. CONCLUSION: The increased utilization
of intravenous acetaminophen in multimodal pain management did not result in an
improved safety or tolerability profile or reduced opioid utilization in
orthopedic patients.
PMID- 28507730
TI - Application of the adverse outcome pathway (AOP) concept to structure the
available in vivo and in vitro mechanistic data for allergic sensitization to
food proteins.
AB - BACKGROUND: The introduction of whole new foods in a population may lead to
sensitization and food allergy. This constitutes a potential public health
problem and a challenge to risk assessors and managers as the existing
understanding of the pathophysiological processes and the currently available
biological tools for prediction of the risk for food allergy development and the
severity of the reaction are not sufficient. There is a substantial body of in
vivo and in vitro data describing molecular and cellular events potentially
involved in food sensitization. However, these events have not been organized in
a sequence of related events that is plausible to result in sensitization, and
useful to challenge current hypotheses. The aim of this manuscript was to collect
and structure the current mechanistic understanding of sensitization induction to
food proteins by applying the concept of adverse outcome pathway (AOP). MAIN
BODY: The proposed AOP for food sensitization is based on information on
molecular and cellular mechanisms and pathways evidenced to be involved in
sensitization by food and food proteins and uses the AOPs for chemical skin
sensitization and respiratory sensitization induction as templates. Available
mechanistic data on protein respiratory sensitization were included to fill out
gaps in the understanding of how proteins may affect cells, cell-cell
interactions and tissue homeostasis. Analysis revealed several key events (KE)
and biomarkers that may have potential use in testing and assessment of proteins
for their sensitizing potential. CONCLUSION: The application of the AOP concept
to structure mechanistic in vivo and in vitro knowledge has made it possible to
identify a number of methods, each addressing a specific KE, that provide
information about the food allergenic potential of new proteins. When applied in
the context of an integrated strategy these methods may reduce, if not replace,
current animal testing approaches. The proposed AOP will be shared at the
www.aopwiki.org platform to expand the mechanistic data, improve the confidence
in each of the proposed KE and key event relations (KERs), and allow for the
identification of new, or refinement of established KE and KERs.
PMID- 28507736
TI - Mark E Josephson The Elegance of Genius. . .
PMID- 28507737
TI - Mark E Josephson: Characteristics of Leadership.
AB - Mark Josephson is without a doubt the most fascinating person I have ever met. I
am proud to have had a close friendship with him and I miss him immensely. I have
written in the past about his amazing academic contributions, but in a way I am
relieved that this is not my topic today. I will instead talk about the unique
aspects of his personality that allowed him to be a great leader in the field of
electrophysiology and a powerful influence on the personal development of those
of us who had the great good fortune of interacting with him closely.
PMID- 28507739
TI - "What Would He Do Next?"
PMID- 28507740
TI - Mark Josephson: Pioneer, Educator and Mentor to a Generation of Cardiac
Electrophysiologists.
AB - In January 2017 we lost a giant in cardiac electrophysiology, whose work and
teachings touched all of us working in the field. Mark Josephson's early work,
building on the work of Hein Wellens in using programmed stimulation and catheter
mapping to understand scar-related ventricular tachycardias, led the way to
surgical and then catheter ablation as a viable therapy for that arrhythmia. His
seminal observations are many and catalogued in 'The Josephson School' a
wonderful book with 59 Chapters and extensive commentary devoted to his
research.1 In the area of scar-related VT alone his work characterising
electrograms in infarct scars and defining their relation to reentry circuits led
to the development of substrate mapping techniques in common use today. His
attention to the details of recording techniques helped establish the standards
for electrophysiology studies. His investigational studies are not limited to
ventricular arrhythmias but extend across the spectrum of cardiac
electrophysiology. He was a superb observer with a talent for recognising subtle,
unexpected events and delving deep to explore their potential mechanisms and
significance.
PMID- 28507735
TI - Does dysfunction of the autonomic nervous system affect success of renal
denervation in reducing blood pressure?
AB - OBJECTIVES: Renal denervation is an interventional approach aiming to reduce high
blood pressure. Its efficacy is subject of controversial debate. We analyzed
autonomic function in patients undergoing renal denervation to identify
responders. METHODS: A total of 21 patients with treatment-resistant hypertension
scheduled for renal denervation were included. Heart rate variability, pupillary
function and sympathetic skin response were examined prior to intervention.
Before and 1 or 3 months after intervention, 24-h ambulatory blood pressure
readings were taken. RESULTS: Patients were stratified according to sympathetic
nervous system function. Sympathetic activity was reduced in 12 participants
(group 1) and normal or enhanced in nine patients (group 2). The mean of daytime
systolic blood pressure decreased in groups 1 and 2 from 168 to 157 mmHg (95%
confidence interval for difference, 1-21 mmHg, p = 0.035) and from 166 to 145
mmHg (8-34 mmHg, p = 0.005), respectively. In a linear model, blood pressure
reduction was 11.3 mmHg (0.3-22 mmHg) greater in group 2 than in group 1 (p =
0.045). CONCLUSION: Patients with preexisting reduced activity of the sympathetic
nervous system benefited less from renal denervation.
PMID- 28507738
TI - Mark E Josephson: Clinical Investigator.
AB - Mark E Josephson entered the world of clinical cardiac electrophysiology (EP)
almost at its inception (1972); with so much to learn and so many directions one
could take, he dived into the field with unbridled enthusiasm and an uncommon -
perhaps almost unique - aptitude for asking questions and finding ways to answer
them. Few aspects of EP escaped his indelible influence. In this short paper, I
will attempt to touch on some of the high points of his astounding career as a
clinical investigator.
PMID- 28507741
TI - Mark Josephson and the ICD: A Personal Perspective.
AB - Mark Josephson dedicated his career to the prevention of premature sudden cardiac
death (SCD). Toward that goal, he was an early adopter of the implantable
cardioverter defibrillator (ICD) and indefatigable advocate for better ICD
technology,[1] both as a clinical tool and as living laboratory to study SCD in
ambulatory patients. With characteristic intellectual integrity and analytical
rigour, he sought an honest and balanced appraisal of the life-saving benefits
and serious complications of this unique therapy.
PMID- 28507742
TI - Mark E Josephson: The Boston Years.
AB - Mark Josephson came to Beth Israel Hospital from the University of Pennsylvania
in 1992, having firmly established a reputation as a master clinician, scientist
and educator. He had built one of the premier electrophysiology (EP) services in
the world in Pennsylvania and had become Chief of Cardiology there by the age of
35. In those days, Beth Israel was well known for its interventional cardiology
and cardiac imaging but had not yet committed to the development of a modern EP
section. The buzz surrounding Mark's arrival predicted an outspoken, larger than
life and irreverent character who would profoundly change the place.
PMID- 28507744
TI - Mahaim Accessory Pathways.
AB - The term Mahaim conduction is conventionally used to describe decrementally
conducting connections between the right atrium or the AV node and the right
ventricle in or close to the right bundle branch. Although such pathways are
rare, their unique properties make their diagnosis and treatment cumbersome. In
this article we review the published evidence, and discuss the
electrocardiographic and electrophysiological characteristics as well as the
anatomy and origin of these fibres.
PMID- 28507743
TI - Electrophysiological Testing for the Investigation of Bradycardias.
AB - In this article we review the role of electrophysiological testing in patients
presenting with bradycardia due to sinus node or atrioventricular node disease.
In sinus bradycardia the role of electrophysiology studies is not established. In
AV conduction disturbances, an electrophysiology study may be necessary both for
the establishment of atrioventricular block as the main cause of symptoms, and
for identification of the anatomic site of block that may dictate the potential
need of permanent pacing.
PMID- 28507747
TI - The clinical and cost implications of failed endoscopic hemostasis in
gastroduodenal ulcer bleeding.
AB - AIM: The aim of this article is to evaluate the clinical and cost implications of
failed endoscopic hemostasis in patients with gastroduodenal ulcer bleeding.
METHODS: A retrospective claims analysis of the Medicare Provider Analysis and
Review (MedPAR) file was conducted to identify all hospitalizations for
gastroduodenal ulcer bleeding in the year 2012. The main outcome measures were to
compare all-cause mortality, total length of hospital stay (LOS), hospital costs
and payment between patients managed with one upper gastrointestinal (UGI)
endoscopy versus more than one UGI endoscopy or requiring interventional
radiology-guided hemostasis (IRH) or surgery after failed endoscopic attempt.
RESULTS: The MedPAR claims data evaluated 13,501 hospitalizations, of which
12,242 (90.6%) reported one UGI endoscopy, 817 (6.05%) reported >1 UGI endoscopy,
303 (2.24%) reported IRH after failed endoscopy and 139 (1.03%) reported
surgeries after failed endoscopy. All cause-mortality was significantly lower for
patients who underwent only one UGI endoscopy (3%) compared to patients requiring
>1 endoscopy (6%), IRH (9%) or surgery (14%), p < 0.0001. The median LOS was
significantly lower for patients who underwent only one UGI endoscopy (four days)
compared to patients requiring >1 endoscopy (eight days), IRH (nine days) or
surgery (15 days), p < 0.0001. The median hospital costs were significantly lower
for patients who underwent one UGI endoscopy ($10,518) compared to patients
requiring >1 endoscopy ($20,055), IRH ($34,730) or surgery ($47,589), p < 0.0001.
CONCLUSIONS: Failure to achieve hemostasis at the index endoscopy has significant
clinical and cost implications. When feasible, a repeat endoscopy must be
attempted followed by IRH. Surgery should preferably be reserved as a last resort
for patients who fail other treatment measures.
PMID- 28507746
TI - Guidelines on eosinophilic esophagitis: evidence-based statements and
recommendations for diagnosis and management in children and adults.
AB - INTRODUCTION: Eosinophilic esophagitis (EoE) is one of the most prevalent
esophageal diseases and the leading cause of dysphagia and food impaction in
children and young adults. This underlines the importance of optimizing diagnosys
and treatment of the condition, especially after the increasing amount of
knowledge on EoE recently published. Therefore, the UEG, EAACI ESPGHAN, and
EUREOS deemed it necessary to update the current guidelines regarding conceptual
and epidemiological aspects, diagnosis, and treatment of EoE. METHODS: General
methodology according to the Appraisal of Guidelines for Research and Evaluation
(AGREE) II and the Grading of Recommendations Assessment, Development, and
Evaluation (GRADE) system was used in order to comply with current standards of
evidence assessment in formulation of recommendations. An extensive literature
search was conducted up to August 2015 and periodically updated. The working
group consisted of gastroenterologists, allergists, pediatricians,
otolaryngologists, pathologists, and epidemiologists. Systematic evidence-based
reviews were performed based upon relevant clinical questions with respect to
patient-important outcomes. RESULTS: The guidelines include updated concept of
EoE, evaluated information on disease epidemiology, risk factors, associated
conditions, and natural history of EoE in children and adults. Diagnostic
conditions and criteria, the yield of diagnostic and disease monitoring
procedures, and evidence-based statements and recommendation on the utility of
the several treatment options for patients EoE are provided. Recommendations on
how to choose and implement treatment and long-term management are provided based
on expert opinion and best clinical practice. CONCLUSION: Evidence-based
recommendations for EoE diagnosis, treatment modalities, and patients' follow up
are proposed in the guideline.
PMID- 28507745
TI - Performance measures for lower gastrointestinal endoscopy: a European Society of
Gastrointestinal Endoscopy (ESGE) quality improvement initiative.
AB - The European Society of Gastrointestinal Endoscopy and United European
Gastroenterology present a short list of key performance measures for lower
gastrointestinal endoscopy. We recommend that endoscopy services across Europe
adopt the following seven key performance measures for lower gastrointestinal
endoscopy for measurement and evaluation in daily practice at a center and
endoscopist level: 1 rate of adequate bowel preparation (minimum standard 90%); 2
cecal intubation rate (minimum standard 90%); 3 adenoma detection rate (minimum
standard 25%); 4 appropriate polypectomy technique (minimum standard 80%); 5
complication rate (minimum standard not set); 6 patient experience (minimum
standard not set); 7 appropriate post-polypectomy surveillance recommendations
(minimum standard not set). Other identified performance measures have been
listed as less relevant based on an assessment of their importance, scientific
acceptability, feasibility, usability, and comparison to competing measures.
PMID- 28507749
TI - Splenic volume differentiates complicated and non-complicated celiac disease.
AB - BACKGROUND: Studies in small groups of patients indicated that splenic volume
(SV) may be decreased in patients with celiac disease (CD), refractory CD (RCD)
type II and enteropathy-associated T-cell lymphoma (EATL). OBJECTIVE: The
objective of this article is to evaluate SV in a large cohort of uncomplicated
CD, RCD II and EATL patients and healthy controls. METHODS: The retrospective
cohort consisted of 77 uncomplicated CD (of whom 39 in remission), 29 RCD II, 24
EATL and 12 patients with both RCD II and EATL. The control group included 149
healthy living kidney donors. SV was determined on computed tomography. RESULTS:
The median SV in the uncomplicated CD group was significantly larger than in
controls (202 cm3 (interquartile range (IQR): 154-275) versus 183 cm3 (IQR: 140
232), p = 0.02). After correction for body surface area, age and gender, the
ratio of SV in uncomplicated CD versus controls was 1.28 (95% confidence
interval: 1.20-1.36; p < 0.001). The median SV in RCD II patients (118 cm3 (IQR
83-181)) was smaller than the median SV in the control group (p < 0.001).
CONCLUSION: This study demonstrates large inter-individual variation in SV. SV is
enlarged in uncomplicated CD. The small SV in RCD II may be of clinical relevance
considering the immune-compromised status of these patients.
PMID- 28507748
TI - Comparison of the pull and introducer percutaneous endoscopic gastrostomy
techniques in patients with head and neck cancer.
AB - BACKGROUND AND STUDY AIMS: Percutaneous endoscopic gastrostomy (PEG) in head and
neck cancer (HNC) patients is associated with higher complication and mortality
rates when compared to a general patient population. The pull technique is still
the preferred technique worldwide but it has some limitations. The aim of this
study is to compare the pull and introducer PEG techniques in patients with HNC.
PATIENTS AND METHODS: This study is based on a retrospective analysis of a
prospectively collected database of 309 patients with HNC who underwent PEG in
the Cancer Institute of Sao Paulo. RESULTS: The procedure was performed with the
standard endoscope in 205 patients and the introducer technique was used in 137
patients. There was one procedure-related mortality. Age, sex and albumin level
were similar in both groups. However in the introducer technique group, patients
had a higher tumor stage, a lower Karnofsky status, and presented more frequently
with tracheostomy and trismus. Overall, major, minor, immediate and late
complications and 30-day mortality rates were similar but the introducer
technique group presented more minor bleeding and tube dysfunctions. CONCLUSION:
The push and introducer PEG techniques seem to be both safe and effective but
present different complication profiles. The choice of PEG technique in patients
with HNC should be made individually.
PMID- 28507750
TI - Effects of conventional and a novel colonic-release bile acid sequestrant, A3384,
on fibroblast growth factor 19 and bile acid metabolism in healthy volunteers and
patients with bile acid diarrhoea.
AB - BACKGROUND: Primary bile acid diarrhoea (BAD) is associated with increased bile
acid synthesis and low fibroblast growth factor 19 (FGF19). Bile acid
sequestrants are used as therapy, but are poorly tolerated and may exacerbate
FGF19 deficiency. AIM: The purpose of this study was to evaluate the
pharmacological effects of conventional sequestrants and a colonic-release
formulation preparation of colestyramine (A3384) on bile acid metabolism and
bowel function in patients with BAD. METHODS: Patients with seven-day 75selenium
homocholic acid taurine (SeHCAT) scan retention <10% were randomised in a double
blind protocol to two weeks treatment with twice-daily A3384 250 mg (n = 6), 1 g
(n = 7) or placebo (n = 6). Thirteen patients were taking conventional
sequestrants at the start of the study. Symptoms were recorded and serum FGF19
and 7alpha-hydroxy-4-cholesten-3-one (C4) measured. RESULTS: Median serum FGF19
on conventional sequestrant treatment was 28% lower than baseline values in BAD
(p < 0.05). C4 on conventional sequestrant treatment was 58% higher in BAD (p <
0.001). No changes were seen on starting or withdrawing A3384. A3384 improved
diarrhoeal symptoms, with a median reduction of 2.2 points on a 0-10 Likert scale
compared to placebo, p < 0.05. CONCLUSIONS: Serum FGF19 was suppressed and bile
acid production up-regulated on conventional bile acid sequestrants, but not with
A3384. This colonic-release formulation of colestyramine produced symptomatic
benefit in patients with BAD.
PMID- 28507752
TI - Effective treatment of benign biliary strictures with a removable, fully covered,
self-expandable metal stent: A prospective, multicenter European study.
AB - BACKGROUND: Temporary placement of removable, fully covered, self-expandable
metal stents (fcSEMS) for treatment of benign biliary strictures (BBS) has been
reported to be effective. However, the optimal extraction time point remains
unclear and stent migration has been a major concern. OBJECTIVE: The objective of
this study was to evaluate the efficacy and safety of this treatment modality
using an fcSEMS with a special antimigration design and prolonged stent indwell
time. METHODS: We performed a prospective, single-arm study at six tertiary care
centers in Europe. Patients with BBS underwent endoscopic or percutaneous
implantation of an fcSEMS (GORE(r) VIABIL(r) Biliary Endoprosthesis, W.L. Gore &
Associates, Flagstaff, AZ, USA). The devices were scheduled to be removed nine
months later, and patients were to return for follow-up for an additional 15
months. RESULTS: Forty-three patients were enrolled in the study. Stricture
etiology was chronic pancreatitis in the majority of patients (57.5%). All fcSEMS
were placed successfully, either endoscopically (76.7%) or percutaneously
(23.3%). Stent migration was observed in two patients (5.2%). Primary patency of
the SEMS prior to removal was 73.0%. All attempted stent removals were
successful. At removal, stricture was resolved or significantly improved without
need for further therapy in 78.9% of patients. Stricture recurrence during a
follow-up of two years post-implant was observed in two patients. CONCLUSIONS:
Temporary placement of the fcSEMS is a feasible, safe and effective treatment for
BBS. The design of the device used in this study accounts for very low migration
rates and facilitates easy stent retrieval, even after it has been in place for
up to 11 months.
PMID- 28507753
TI - Yield of magnetic resonance cholangiopancreatography for the investigation of
bile duct dilatation in asymptomatic patients.
AB - BACKGROUND: Biliary dilatation in the asymptomatic patient is a frequent
incidental finding in the work-up for which there are no current guidelines.
OBJECTIVES: The purpose of this study was to determine the yield of magnetic
resonance cholangiopancreatography (MRCP) in asymptomatic patients with an
incidental finding of biliary duct dilatation. METHODS: The study included 68
consecutive patients for evaluation of biliary duct dilatation found incidentally
on computed tomography (CT) or ultrasound (US). MRCP scans were reviewed, and
data were retrospectively collected on demographics and laboratory work-up.
Patients were divided by the presence of a significant or non-significant MRCP
findings explaining the biliary duct dilatation and compared for normal or
abnormal liver function. RESULTS: Liver function was normal in 47 patients and
abnormal in 21 patients. MRCP identified the cause of the bile duct dilatation in
41 patients (60.3%). Rates of insignificant causes were 51% in the normal-liver
function group and 7% in the abnormal-function group. Corresponding rates of
significant causes were 27.7% and 61.9% (p = 0.007). CONCLUSIONS: MRCP is a
valuable tool in the work-up of biliary duct dilatation. Although significantly
more significant causes of bile dilatation are identified in patients with
abnormal liver function, almost one-third of patients with normal liver function
need further work-up. This has important implications for establishing criteria
for the use of MRCP in asymptomatic patients with biliary dilatation.
PMID- 28507751
TI - Validation of the efficacy of the prognostic factor score in the Japanese
severity criteria for severe acute pancreatitis: A large multicenter study.
AB - BACKGROUND: The Japanese severity criteria for acute pancreatitis (AP), which
consist of a prognostic factor score and contrast-enhanced computed tomography
grade, have been widely used in Japan. OBJECTIVE: This large multicenter
retrospective study was conducted to validate the predictive value of the
prognostic factor score for mortality and complications in severe AP patients in
comparison to the Acute Physiology and Chronic Health Evaluation II (APACHE II)
score. METHODS: Data of 1159 patients diagnosed with severe AP according to the
Japanese severity criteria for AP were retrospectively collected in 44
institutions. RESULTS: The area under the curve (AUC) for the receiver-operating
characteristic curve of the prognostic factor score for predicting mortality was
0.78 (95% confidence interval (CI), 0.74-0.82), whereas the AUC for the APACHE II
score was 0.80 (95% CI, 0.76-0.83), respectively. There were no significant
differences in the AUC for predicting mortality between two scoring systems. The
AUCs of the prognostic factor scores for predicting the need for mechanical
ventilation, the development of pancreatic infection, and severe AP according to
the revised Atlanta classification were 0.84 (95% CI, 0.81-0.86), 0.73 (95% CI,
0.69-0.77), and 0.83 (95% CI, 0.81-0.86), respectively, which were significantly
greater than the AUCs for the APACHE II score; 0.81 (95% CI, 0.78-0.83) for the
need for mechanical ventilation (p = 0.03), 0.68 (95% CI, 0.63-0.72) for the
development of pancreatic infection (p = 0.02), and 0.80 (95% CI, 0.77-0.82) for
severe AP according to the revised Atlanta classification (p = 0.01). CONCLUSION:
The prognostic factor score has an equivalent ability for predicting mortality
compared with the APACHE II score. Regarding the ability for predicting the
development of severe complications during the clinical course of AP, the
prognostic factor score may be superior to the APACHE II score.
PMID- 28507754
TI - Significantly higher rates of multiple and proximally located adenomas among
patients with diabetes mellitus: A cross-sectional population-based study.
AB - BACKGROUND: Diabetes mellitus (DM) is associated with a greater risk for
colorectal cancer (CRC). OBJECTIVE: The objective of this article is to examine
the endoscopic phenotype and histopathology of colorectal polyps in patients with
vs without DM. METHODS: We conducted a cross-sectional study of patients who
underwent colonoscopy at our university hospital and who completed a
questionnaire. We collected endoscopy and histopathology data regarding
colorectal adenomas and serrated polyps. Cox regression analyses were used to
estimate adjusted prevalence ratios (PRs). RESULTS: We examined a total of 3654
patients (mean age (SD): 62 (12) years, 47% males). Of them, 360 (9.9%) had DM.
Overall, the prevalence of colorectal adenomas (42% vs 32%, p < 0.01), multiple
(>=3) adenomas (12% vs 7%, p = 0.01) and proximal adenomas (30% vs 19%, p < 0.01)
was higher in patients with vs without DM. Multivariable analysis showed that the
prevalence of adenomas (PR 1.17, 95% CI; 1.02-1.34), multiple (PR 1.37, 95% CI;
1.00-1.86) and proximal (PR 1.37, 95% CI; 1.16-1.62) adenomas was higher in
patients with vs without DM, especially in men. CONCLUSION: Patients with DM
harbor more frequently multiple and proximal adenomas than those without DM.
Close colonoscopic surveillance of DM patients is important to maximize the
effectiveness of colonoscopic CRC prevention.
PMID- 28507755
TI - Ethnic variations in the occurrence of colonic neoplasms.
AB - BACKGROUND AND AIMS: With the exception of African Americans and Hispanics, few
studies have dealt with the influence of other types of ethnicity on the
prevalence of colon polyps and colorectal cancer. The present study was
undertaken to compare the ethnic and socioeconomic distributions of colonic
neoplasms among different ethnic groups in the United States. METHODS: A total of
813,057 patients, who underwent colonoscopy during 2008-2014, were recruited from
an electronic database of histopathology reports (Miraca Life Sciences) for a
cross-sectional study. Using multivariate logistic regression analyses, the
presence of hyperplastic polyps, serrated adenomas, tubular adenomas, or
adenocarcinomas each served as separate outcome variables. Patient ethnicity was
determined using a name-based computer algorithm. Demographic (age, sex,
ethnicity) and a variety of socioeconomic risk factors (associated with patients'
ZIP code) served as predictor variables. RESULTS: About 50% of the study
population harbored adenomatous polyps, 25% hyperplastic polyps, 8% serrated
adenomas, and 1.4% adenocarcinomas. Tubular adenomas and adenocarcinomas showed
similar ethnic distributions, being slightly more common among Hispanics and East
Asians. All four types of colonic neoplasm were relatively rare among patients of
Asian-Indian descent and relatively common among patients of Japanese descent.
Except for Japanese patients, serrated adenomas tended to be less prevalent among
East Asians. In general, markers of high socioeconomic status showed a tendency
to be negatively associated with the presence of tubular adenoma and
adenocarcinoma, but positively with the presence of serrated adenoma. CONCLUSION:
Ethnicity and socioeconomic factors affect different histology types of polyps
differently. Genetic as well as environmental factors interact in the development
of colorectal cancer and its precursor lesions.
PMID- 28507756
TI - Predictive factors of short-term mortality in ischaemic colitis and development
of a new prognostic scoring model of in-hospital mortality.
AB - BACKGROUND: Ischaemic colitis (IC) is the most common form of intestinal
ischaemia with a wide spectrum of severity, with possible risk of death.
OBJECTIVE: The purpose of this study was to evaluate predictive factors of in
hospital and short-term mortality, in a cohort of patients with IC. METHODS:
Retrospective analysis of IC cases diagnosed between 2008-2013 in a single
tertiary centre, with assessment of factors at the time of diagnosis associated
with in-hospital and 90-day mortality. RESULTS: Of the 203 patients included (132
women), 47 (23%) died during the follow-up (median: 16 months). There were 21
patients (45%) who died during hospitalization and at 90 days there were 30
deaths (64% of total). In multivariate analysis, need for vasopressor support
(odds ratio (OR) 11.21; 95% confidence interval (CI): 2.31-54.24; p = 0.01),
Intermediate or Intensive Care Unit (ICU): admission (OR 7.01; 95% CI: 1.48
33.16; p = 0.014) and atrial fibrillation (OR 4.99; 95% CI: 1.1-26.23; p = 0.048)
were independently and significantly associated with in-hospital mortality. Using
the coefficients of the estimated logistic model, we calculated a scoring model
to predict the occurrence of in-hospital mortality. The presence of all three
risk factors predicted a probability of death of 32% with an area under the
receiver operating characteristic curve (AUROC) of 0.89 (95% CI 0.80-0.98. At 90
days, the presence of chronic kidney disease (OR 7.46; 95% CI: 1.87-29.73; p =
0.002), and male sex (OR 5.85; 95% CI: 1.57-21.83; p = 0.009) were also
independently associated with mortality. CONCLUSIONS: Most deaths in ischaemic
colitis occur in the first 90 days after admission, sharing similar risk factors.
Assessment of the presence of atrial fibrillation, need of vasopressor support or
hospitalization in the intermediate/intensive care unit provides a useful tool to
estimate in-hospital mortality and to establish the management for patients
admitted for ischaemic colitis.
PMID- 28507757
TI - Risk of post-colonoscopy colorectal cancer due to incomplete adenoma resection: A
nationwide, population-based cohort study.
AB - BACKGROUND: Most post-colonoscopy colorectal cancers (PC-CRCs) are thought to
develop from missed or incompletely resected adenomas. AIMS: We aimed to assess
the incidence rate of PC-CRC overall and per colorectal segment, as a proxy for
PC-CRC due to incomplete adenoma resection, and to identify adenoma
characteristics associated with these PC-CRCs. METHODS: We performed a
nationwide, population-based cohort study, including all patients with a first
colorectal adenoma between 2000-2010 in the Dutch Pathology Registry (PALGA).
Outcomes were the incidence rate of PC-CRC overall and of PC-CRC in the same
colorectal segment, occurring between six months and five years after adenoma
resection. A multivariable Cox proportional hazard analysis was performed to
identify factors associated with PC-CRCs in the same segment. RESULTS: We
included 107,744 patients (mean age 63.4 years; 53.6% male). PC-CRC was detected
in 1031 patients (0.96%) with an incidence rate of 1.88 per 1000 person years. PC
CRC in the same segment was found in 323 of 133,519 adenomas (0.24%) with an
incidence rate of 0.56 per 1000 years of follow-up. High-grade dysplasia (hazard
ratio (HR) 2.54, 95% confidence interval (CI) 1.99-3.25) and both villous (HR
2.63, 95% CI 1.79-3.87) and tubulovillous histology (HR 1.80, 95% CI 1.43-2.27)
were risk factors for PC-CRC in the same segment. CONCLUSIONS: Approximately one
third of PC-CRCs are found in the same colorectal segment after adenoma resection
and could therefore be a consequence of incomplete adenoma resection, occurring
in one in 400 adenomas. The risk of PC-CRC in the same segment is increased in
adenomas with high-grade dysplasia or (tubulo)villous histology.
PMID- 28507759
TI - Emerging local ablative therapies for unresectable perihilar cholangiocarinoma:
Time for re-appraisal.
PMID- 28507758
TI - Fecal immunochemical test-based colorectal cancer screening: The gender dilemma.
AB - BACKGROUND: Despite differences between men and women in incidence of colorectal
cancer (CRC) and its precursors, screening programs consistently use the same
strategy for both genders. OBJECTIVE: The objective of this article is to
illustrate the effects of gender-tailored screening, including the effects on
miss rates of advanced neoplasia (AN). METHODS: Participants (age 50-75 years) in
a colonoscopy screening program were asked to complete a fecal immunochemical
test (FIT) before colonoscopy. Positivity rates, sensitivity and specificity for
detection of AN at multiple cut-offs were determined. Absolute numbers of
detected and missed AN per 1000 screenees were calculated. RESULTS: In total
1,256 individuals underwent FIT and colonoscopy, 51% male (median age 61 years;
IQR 56-66) and 49% female (median age 60 years; IQR 55-65). At all cut-offs men
had higher positivity rates than women, ranging from 3.8% to 10.8% versus 3.2% to
4.8%. Sensitivity for AN was higher in men than women; 40%-25% and 35%-22%,
respectively. More AN were found and missed in absolute numbers in men at all cut
offs. CONCLUSION: More AN were both detected and missed in men compared to women
at all cut-offs. Gender-tailored cut-offs could either level sensitivity in men
and women (i.e., lower cut-off in women) or level the amount of missed lesions
(i.e., lower cut-off in men).
PMID- 28507760
TI - Young GI Angle - Harmonised education: the EBGH Blue Book.
PMID- 28507761
TI - The European Section and Board of Gastroenterology and Hepatology.
PMID- 28507762
TI - Circulating tumor cell clusters-associated gene plakoglobin is a significant
prognostic predictor in patients with breast cancer.
AB - BACKGROUND: Circulating tumor cells (CTCs) are linked to metastatic relapse and
are regarded as a prognostic marker for human cancer. High expression of
plakoglobin, a cell adhesion protein, within the primary tumor is positively
associated with CTC clusters in breast cancer. In this study, we investigated the
correlation between plakoglobin expression and survival of breast cancer.
METHODS: We evaluated 121 breast cancer patients treated with neoadjuvant
chemotherapy. Expression of plakoglobin was identified by immunohistochemical
staining in the cell membrane. We also examined the relation between the
expression of plakoglobin and E-cadherin, an epithelial-mesenchymal transition
(EMT) marker. RESULTS: Patients with high plakoglobin expression had
significantly worse distant-metastasis-free survival (DMFS) (P = 0.016, log
rank). Plakoglobin expression had no correlation with pathological complete
response rate (P = 0.627). On univariate analysis with respect to distant
metastasis, high plakoglobin expression showed worse prognosis than low
plakoglobin expression [P = 0.036, hazard ratio (HR) = 3.719]. Multivariate
analysis found the same result (P = 0.013, HR = 5.052). In addition, there was a
significant relationship between the expression of plakoglobin and E-cadherin (P
= 0.023). CONCLUSIONS: Plakoglobin expression is an independent prognostic factor
in patients with breast cancer, particularly for DMFS, and this is related to
EMT.
PMID- 28507763
TI - Investigation of cloud point extraction for the analysis of metallic
nanoparticles in a soil matrix.
AB - The characterization of manufactured nanoparticles (MNPs) in environmental
samples is necessary to assess their behavior, fate and potential toxicity.
Several techniques are available, but the limit of detection (LOD) is often too
high for environmentally relevant concentrations. Therefore, pre-concentration of
MNPs is an important component in the sample preparation step, in order to apply
analytical tools with a LOD higher than the ng kg-1 level. The objective of this
study was to explore cloud point extraction (CPE) as a viable method to pre
concentrate gold nanoparticles (AuNPs), as a model MNP, spiked into a soil
extract matrix. To that end, different extraction conditions and surface coatings
were evaluated in a simple matrix. The CPE method was then applied to soil
extract samples spiked with AuNPs. Total gold, determined by inductively coupled
plasma mass spectrometry (ICP-MS) following acid digestion, yielded a recovery
greater than 90 %. The first known application of single particle ICP-MS and
asymmetric flow field-flow fractionation to evaluate the preservation of the AuNP
physical state following CPE extraction is demonstrated.
PMID- 28507764
TI - 'Actinomyces provencensis' sp. nov., 'Corynebacterium bouchesdurhonense' sp.
nov., 'Corynebacterium provencense' sp. nov. and 'Xanthomonas massiliensis' sp.
nov., 4 new species isolated from fresh stools of obese French patients.
AB - We report the main characteristics of 'Actinomyces provencensis' strain SN12T sp.
nov., 'Corynebacterium bouchesdurhonense' strain SN14T sp. nov., 'Corynebacterium
provencense' strain SN15T sp. nov. and 'Xanthomonas massiliensis' strain SN8T sp.
nov., which were all isolated from stool samples from obese French patients.
PMID- 28507765
TI - Asthma: epidemiology of disease control in Latin America - short review.
AB - Asthma is reported as one of the most common chronic diseases in childhood,
impairing the quality of life of patients and their families and incurring high
costs to the healthcare system and society. Despite the development of new drugs
and the availability of international treatment guidelines, asthma is still
poorly controlled, especially in Latin America. Original and review articles on
asthma control or epidemiology with high levels of evidence have been selected
for analysis among those published in PubMed referenced journals during the last
20 years, using the following keywords: "asthma control" combined with "Latin
America", " epidemiology", "prevalence", "burden", "mortality", "treatment and
unmet needs", "children", "adolescents", and "infants". There was a high
prevalence and severity of asthma during the period analyzed, especially in
children and adolescents. Wheezing in infants was a significant reason for
seeking medical care in Latin American health centers. Moreover, the frequent use
of quick-relief bronchodilators and oral corticosteroids by these patients
indicates the lack of a policy for providing better care for asthmatic patients,
as well as poor asthma control. Among adults, studies document poor treatment and
control of the disease, as revealed by low adherence to routine anti-inflammatory
medications and high rates of emergency care visits and hospitalization. In
conclusion, although rare, studies on asthma control in Latin America repeatedly
show that patients are inadequately controlled and frequently overestimate their
degree of asthma control according to the criteria used by international asthma
treatment guidelines. Additional education for doctors and patients is essential
for adequate control of this illness, and therefore also for reduction of the
individual and social burden of asthma.
PMID- 28507766
TI - Effect of dietary mannanoligosaccharide supplementation on nutrient
digestibility, hindgut fermentation, immune response and antioxidant indices in
dogs.
AB - BACKGROUND: Use of prebiotics in companion animal nutrition is often considered
advantageous over probiotics because of the ease of handling, ability to
withstand processing and storage etc. While most of the studies on prebiotic use
in dogs have been done with processed food as basal diet, the response in
relation to homemade diet feeding is not very well explored. METHODS: The study
was conducted to evaluate the effects of dietary mannanoligosaccharide (MOS)
supplementation on nutrient digestibility, hindgut fermentation, immune response
and antioxidant indices in dogs. Ten Spitz pups were divided into two groups:
control (CON) with no supplementation, and experimental (MOS) wherein the basal
diet was supplemented with MOS at 15 g/kg diet. All dogs were fed on a home
prepared diet for a period of 150 days. The study protocol included a digestion
trial, periodic blood collection and analysis for lipid profile and erythrocytic
antioxidants. Immune response of the animals was assessed towards the end of the
feeding period. RESULTS: Results revealed no significant (P > 0.05) variations in
palatability score, intake and apparent digestibility of nutrients between the
groups. Faecal score, faeces voided, faecal pH, concentrations of ammonia,
lactate and short-chain fatty acids were comparable (P > 0.05) between the two
groups. Cell-mediated immune response, assessed as delayed-type of
hypersensitivity response, was significantly higher (P < 0.05) in the MOS group.
The percent of lymphocyte sub-populations CD4+ and ratio of CD4+:CD8+ were also
significantly (P < 0.05) higher in MOS group. The serum IgG levels were similar
(P > 0.05) in both the groups. Supplementation of MOS lowered (P < 0.05) serum
total- and LDL- cholesterol levels, when compared with the control group. The
erythrocytic antioxidant indices were similar (P > 0.05) between the two groups.
CONCLUSIONS: The results indicated that supplementation of MOS at the rate of 15
g/kg in the diet of dog augmented the cell-mediated immune response and serum
lipid profile without any influences on digestibility of nutrients, hindgut
fermentation and antioxidants indices.
PMID- 28507767
TI - Post-traumatic stress in pregnant women with primary cytomegalovirus infection
and risk of congenital infection in newborns.
AB - BACKGROUND: Substantial evidence indicates that perinatal mental disturbances are
associated with the risk for negative maternal-newborn outcomes. A neuroendocrine
brain-placenta interaction has been described to explain the association between
prenatal stress-related disorders and placental abnormalities. Whether these
mechanisms may affect the likelihood of mother-to-child transmission (MTCT) of
infections has never been investigated. AIMS: To evaluate the role of
psychological factors in cytomegalovirus (CMV) MTCT in pregnant women with
primary CMV infection. METHOD: A cohort of 276 pregnant women with primary CMV
infection underwent assessment of (a) reactive psychopathological symptoms, such
as current depressive symptoms and ongoing symptoms of post-traumatic stress
disorder; and (b) stable personality traits, such as alexithymia and Type D
(distressed) personality. Congenital infection was diagnosed by CMV DNA
amplification from blood and/or urine and saliva from newborn at birth. RESULTS:
The occurrence of congenital CMV disease in the newborn was independently
predicted by post-traumatic stress symptoms during pregnancy. CONCLUSIONS: Our
findings suggest that psychological stress-related disturbances may weaken the
physical and immunological barrier against the mother-to-fetus transmission of
viruses. DECLARATION OF INTEREST: We declare that we have no conflicting
interests to disclose. COPYRIGHT AND USAGE: (c) The Royal College of
Psychiatrists 2016. This is an open access article distributed under the terms of
the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.
PMID- 28507768
TI - In-patient suicide: selection of people at risk, failure of protection and the
possibility of causation.
AB - BACKGROUND: Being a current psychiatric in-patient is one of the strongest
statistical risk factors for suicide. It is usually assumed that this strong
association is not causal but is a result of the combination of the selection of
high-risk patients for admission and the imperfect protection from suicide
afforded by psychiatric wards. Logically, a third factor, which is causal, might
play a role in the association. It has recently been suggested that adverse
experiences in psychiatric units such as trauma, stigma and loss of social role
might precipitate some in-patient suicides. AIMS: To consider whether there is a
causal association between psychiatric hospitalisation and suicide. METHOD: We
used the framework of Austin Bradford Hill's criteria for assessing causality in
epidemiology to consider the possibility that psychiatric hospitalisation might
causally contribute to the extent and variation in in-patient suicide rates.
RESULTS: The association between psychiatric hospitalisation and suicide clearly
meets five of the nine Hill's criteria (strength of association, consistency,
plausibility, coherence and analogy) and partially meets three of the remaining
four criteria (gradient of exposure, temporality and experimental evidence).
CONCLUSIONS: Admission to hospital itself might play a causal role in a
proportion of in-patient suicides. The safety of being in hospital with respect
to suicide could be examined with a large-scale randomised controlled trial
(RCT). In the absence of an RCT, the possibility of a causal role provides
further impetus to calls to make care in the community more available and
psychiatric hospitals more acceptable to patients. DECLARATION OF INTEREST:
M.M.L. and C.J.R. have provided expert testimony in legal proceedings following
in-patient suicide. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists
2017. This is an open access article distributed under the terms of the Creative
Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.
PMID- 28507769
TI - A National Quality Improvement Collaborative for the clinical use of outcome
measurement in specialised mental healthcare: results from a parallel group
design and a nested cluster randomised controlled trial.
AB - BACKGROUND: Although the importance and advantages of measurement-based care in
mental healthcare are well established, implementation in daily practice is
complex and far from optimal. AIMS: To accelerate the implementation of outcome
measurement in routine clinical practice, a government-sponsored National Quality
Improvement Collaborative was initiated in Dutch-specialised mental healthcare.
METHOD: To investigate the effects of this initiative, we combined a matched-pair
parallel group design (21 teams) with a cluster randomised controlled trial (RCT)
(6 teams). At the beginning and end, the primary outcome 'actual use and
perceived clinical utility of outcome measurement' was assessed. RESULTS: In both
designs, intervention teams demonstrated a significant higher level of
implementation of outcome measurement than control teams. Overall effects were
large (parallel group d=0.99; RCT d=1.25). CONCLUSIONS: The National
Collaborative successfully improved the use of outcome measurement in routine
clinical practice. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The
Royal College of Psychiatrists 2017. This is an open access article distributed
under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC
ND) license.
PMID- 28507771
TI - Association between suicidal symptoms and repeat suicidal behaviour within a
sample of hospital-treated suicide attempters.
AB - BACKGROUND: Suicidal behaviour is the end result of the complex relation between
many factors which are biological, psychological and environmental in nature.
Network analysis is a novel method that may help us better understand the complex
association between different factors. AIMS: To examine the relationship between
suicidal symptoms as assessed by the Beck Scale for Suicide Ideation and future
suicidal behaviour in patients admitted to hospital following a suicide attempt,
using network analysis. METHOD: Secondary analysis was conducted on previously
collected data from a sample of 366 patients who were admitted to a Scottish
hospital following a suicide attempt. Network models were estimated to visualise
and test the association between baseline symptom network structure and suicidal
behaviour at 15-month follow-up. RESULTS: Network analysis showed that the desire
for an active attempt was found to be the most central, strongly related suicide
symptom. Of the 19 suicide symptoms that were assessed at baseline, 10 symptoms
were directly related to repeat suicidal behaviour. When comparing baseline
network structure of repeaters (n=94) with the network of non-repeaters (n=272),
no significant differences were found. CONCLUSIONS: Network analysis can help us
better understand suicidal behaviour by visualising the complex relation between
relevant symptoms and by indicating which symptoms are most central within the
network. These insights have theoretical implications as well as informing the
assessment and treatment of suicidal behaviour. DECLARATION OF INTEREST: None.
COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2017. This is an open
access article distributed under the terms of the Creative Commons Non
Commercial, No Derivatives (CC BY-NC-ND) license.
PMID- 28507770
TI - The recovery of factors associated with decision-making capacity in individuals
with psychosis.
AB - BACKGROUND: There is limited data on the recovery of factors associated with
decisional capacity in patients with psychosis. AIMS: To study the relationship
between changes in mental capacity, symptoms and global functioning using
structured measures during treatment for psychosis. METHOD: Fifty-six patients
with psychosis were assessed for capacity to consent to treatment on admission
and at 6 and 12 weeks following treatment. The MacArthur Competence Assessment
Tool - Treatment, the Positive and Negative Symptom Scale and the Global
Assessment of Functioning Scale were used to measure mental capacities, symptom
severity and global functioning respectively. Treating consultants rated capacity
to consent, masked to these measures. RESULTS: Greater impairments on all
measures were found in patients assessed as lacking capacity. These improved with
treatment over 12 weeks with significant effect sizes (0.5 to 0.6). Stronger
correlations between mental capacities, positive symptoms (-0.47) and global
functioning (0.56) were noted in the first 6 weeks. CONCLUSIONS: Impairments in
capacity in acute stages of psychosis are related to symptom severity and
functional impairment. They improve during treatment, particularly in the first 6
weeks. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College
of Psychiatrists 2017. This is an open access article distributed under the terms
of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.
PMID- 28507773
TI - Rapid-onset clozapine-induced loss of glycaemic control: case report.
AB - : Clozapine has proved to be an effective antipsychotic for the treatment of
refractory schizophrenia - characterised by the persistence of symptoms despite
optimal treatment trials with at least two different antipsychotics at adequate
dose and duration - but its use is hampered by adverse effects. The development
of clozapine-induced diabetes is commonly considered to arise as part of a
metabolic syndrome, associated with weight gain, and thus evolves slowly. We
present the case of an individual with refractory schizophrenia and metformin
controlled diabetes who developed rapid-onset insulin-dependent hyperglycaemia
immediately after starting clozapine. Given the refractory nature of his illness,
the decision was made to continue clozapine and manage the diabetes. This case
supports the existence of a more direct mechanism by which clozapine alters
glycaemic control, aside from the more routine slow development of a metabolic
syndrome. DECLARATION OF INTEREST: S.S.S. is supported by a European Research
Council Consolidator Award (Grant Number 311686) and the National Institute for
Health Research (NIHR) Mental Health Biomedical Research Centre at South London
and Maudsley NHS Foundation Trust and King's College London. The funders had no
role in study design, data collection, data analysis, data interpretation or
writing of the report. COPYRIGHT AND USAGE: (c) The Royal College of
Psychiatrists 2017. This is an open access article distributed under the terms of
the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.
PMID- 28507772
TI - Clinically significant depressive symptoms and sexual behaviour among men who
have sex with men.
AB - BACKGROUND: The relationship between depression and sexual behaviour among men
who have sex with men (MSM) is poorly understood. AIMS: To investigate prevalence
and correlates of depressive symptoms (Patient Health Questionnaire-9 score >=10)
and the relationship between depressive symptoms and sexual behaviour among MSM
reporting recent sex. METHOD: The Attitudes to and Understanding of Risk of
Acquisition of HIV (AURAH) is a cross-sectional study of UK genitourinary
medicine clinic attendees without diagnosed HIV (2013-2014). RESULTS: Among 1340
MSM, depressive symptoms (12.4%) were strongly associated with socioeconomic
disadvantage and lower supportive network. Adjusted for key sociodemographic
factors, depressive symptoms were associated with measures of condomless sex
partners in the past 3 months (>=2 (prevalence ratio (PR) 1.42, 95% CI 1.17-1.74;
P=0.001), unknown or HIV-positive status (PR 1.43, 95% CI 1.20-1.71; P<0.001)),
sexually transmitted infection (STI) diagnosis (PR 1.46, 95% CI 1.19-1.79;
P<0.001) and post-exposure prophylaxis use in the past year (PR 1.83, 95% CI 1.33
2.50; P<0.001). CONCLUSIONS: Management of mental health may play a role in HIV
and STI prevention. DECLARATION OF INTEREST: A.N.P. has received payments for
presentations made at meetings sponsored by Gilead in spring 2015. N.C.N. has
received support for attendance at conferences, speaker fees and payments for
attendance at advisory boards from Gilead Sciences, Viiv Healthcare, Janssen
Pharmaceuticals and Bristol-Myers Squibb and a research grant from Gilead
Sciences. D.A. served on the advisory board for Gilead in January 2016. M.M.G.
has had sponsorship to attend conferences by Bristol-Myers Squibb, been on the
BioCryst advisory board and run trials for Merck, Gilead, SSAT, BioCryst and
Novartis. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2017. This
is an open access article distributed under the terms of the Creative Commons Non
Commercial, No Derivatives (CC BY-NC-ND) license.
PMID- 28507774
TI - Footnotes to Kraepelin: changes in the classification of mood disorders with DSM
5.
AB - SUMMARY: Reliable diagnosis of mood disorders continues to pose a challenge. This
is surprising because they have been recognised clinically since classical times.
Mood disorders are also common: major depressive disorder affects nearly 300
million people worldwide and bipolar affective disorder nearly 60 million and
they are a major cause of disability. Nonetheless, the reliability trials of the
updated Diagnostic and Statistical Manual, Fifth Edition (DSM-5) found that the
reliability of the diagnosis of major depressive disorder was in the
'questionable' range. Although the reliability of the diagnosis of bipolar I
disorder in the same trials was 'good', the sample size of the individuals
recruited to validate bipolar II disorder was insufficient to confirm
reliability. As the epidemiological prevalences of bipolar I and bipolar II
disorders are the same, this alone implies problems in its recognition. Here, we
critically evaluate the most recent iteration of DSM mood disorder diagnoses in a
historical light and set out the implications for clinical practice and research.
DECLARATION OF INTEREST: N.J.K. has attended educational activities funded by
GlaxoSmithKline (GSK) and by Lundbeck and has worked on data from a study funded
by Wyeth; her PhD was jointly funded by the Wellcome Trust and GSK. A.H.Y. has
given paid lectures and is on advisory boards for the following companies with
drugs used in affective and related disorders: Astrazenaca, Eli Lilly, Janssen,
Lundeck, Sunovion, Servier, Livanova. He is Lead Investigator for the Embolden
Study (Astrazenaca), BCI Neuroplasticity study and Aripiprazole Mania Study,
which are investigator-initiated studies from Astrazenaca, Eli Lilly, Lundbeck,
and Wyeth. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2017. This
is an open access article distributed under the terms of the Creative Commons Non
Commercial, No Derivatives (CC BY-NC-ND) license.
PMID- 28507775
TI - Thoracolumbar fractures without neurological impairment: A review of diagnosis
and treatment.
AB - An appropriate protocol and unified management of thoracolumbar fractures without
neurological impairment has not been well defined.This review attempts to
elucidate some controversies regarding diagnostic tools, the ability to define
the most appropriate treatment of classification systems and the evidence for
conservative and surgical methods based on the recent literature. Cite this
article: Vila-Canet G, Garcia de Frutos A, Covaro A, Ubierna MT, Caceres E.
Thoracolumbar fractures without neurological impairment: a review of diagnosis
and treatment. EFORT Open Rev 2016;1:332-338. DOI: 10.1302/2058-5241.1.000029.
PMID- 28507776
TI - The current situation in hip arthroscopy.
AB - Hip arthroscopy is an evolving surgical technique that has recently increased in
popularity.Although femoroacetabular impingement was an important launch pad for
this technique, extra-articular pathology has been described through hip
endoscopy.Good clinical results in the medium term will allow improvements in
this technique and increase its indications. Cite this article: EFORT Open Rev
2017;2:58-65. DOI: 10.1302/2058-5241.2.150041.
PMID- 28507780
TI - Current concepts in elbow arthroplasty.
AB - Distal humeral replacement and the total elbow are two commonly-used
arthroplastiesEach prosthesis has evolving indications and surgical
techniquesRecent changes in device design and implantation methods are due to
biomechanical and clinical outcome-based researchNew prostheses and methods
provide: better elbow kinematics, more durable bearings and longer-lasting joint
replacement potential Cite this article: EFORT Open Rev 2017;2:83-88. DOI:
10.1302/2058-5241.2.160064.
PMID- 28507777
TI - The role of isolated polyethylene exchange in total knee arthroplasty.
AB - The use of modular total knee arthroplasty (TKA) implants allows surgeons to
perform isolated tibial polyethylene insert exchange (IPE) while retaining well
fixed and stable components.The purported advantages of IPE include preservation
of bone stock, shorter operating time, less blood loss, faster rehabilitation and
lower cost. However, the indications for IPE are limited.IPE for wear and
osteolysis has moderate success in the medium term but should be avoided in cases
of accelerated wear. In selected cases, debridement and IPE for early infection
can result in low morbidity with high success rates in the short term. IPE for
arthrofibrosis has poor results.IPE should be undertaken with caution and an
institutional algorithm should be followed. Cite this article: EFORT Open Rev
2017;2:66-71 DOI: 10.1302/2058-5241.2.160049.
PMID- 28507779
TI - Spinal osteotomies: indications, limits and pitfalls.
AB - The aims of spinal deformity surgery are to achieve balance, relieve pain and
prevent recurrence or worsening of the deformity.The main types of osteotomies
are the Smith-Petersen osteotomy (SPO), pedicle subtraction osteotomy (PSO), bone
disc-bone osteotomy (BDBO) and vertebral column resection (VCR), in order of
increasing complexity.SPO is a posterior column osteotomy in which the posterior
ligaments and the facet joints are removed and correction is performed through
the disc space. A mobile anterior disc is essential. SPO is best in patients with
+6-8 cm C7 plumbline. The amount of correction is 9.3 degrees to 10.7 degrees
/level (1 degrees /mm bone).PSO is a technique where the posterior elements and
pedicles are removed. Then a triangular wedge through the pedicles is removed and
the posterior spine is shortened using the anterior cortex as a hinge. The ideal
candidates are patients with a severe sagittal imbalance. A single level
osteotomy can produce 30 degrees 40 degrees of correction. A single level
osteotomy may restore global sagittal balance by an average of 9 cm with an upper
limit of 19 cm.BDBO is an osteotomy done above and below a disc level. A BDBO
provides correction rates in the range of 35 degrees to 60 degrees . The main
indications are deformities with the disc space as the apex and severe sagittal
plane deformities.VCR is indicated for rigid multi-planar deformities, sharp
angulated deformities, hemivertebra resections, resectable spinal tumours, post
traumatic deformities and spondyloptosis. The main indication for a VCR is fixed
coronal plane deformity.The type of osteotomy must be chosen mainly according to
the aetiology, type and apex of the deformity. One may start with SPOs and may
gradually advance to complex osteotomies. Cite this article: EFORT Open Rev
2017;2:73-82. DOI: 10.1302/2058-5241.2.160069.
PMID- 28507781
TI - Isolated posterior cruciate ligament tears: an update of management.
AB - Isolated posterior cruciate ligament (PCL) tears are much less frequent than
anterior cruciate ligament (ACL) tears.Abrupt posterior tibial translation (such
as dashboard impact), falls in hyperflexion and direct hyperextension trauma are
the most frequent mechanisms of production.The anterolateral bundle represents
two-thirds of PCL mass and is reconstructed in single-bundle techniques.The PCL
has an intrinsic capability for healing. This is the reason why, nowadays, the
majority of isolated PCL tears are managed non-operatively, with rehabilitation
and bracing.Recent studies have focused on double-bundle reconstruction
techniques, as they seem to restore knee kinematics.No significant clinical
differences have been established between single versus double-bundle techniques,
autograft versus allograft, transtibial tunnel versus tibial inlay techniques or
remnant-preserving versus remnant-release techniques. Cite this article: EFORT
Open Rev 2017;2:89-96. DOI: 10.1302/2058-5241.2.160009.
PMID- 28507782
TI - Surgical treatment of acetabular fractures in the elderly: a systematic review of
the results.
AB - We performed a systematic review of the literature involving a number of
databases to identify studies that included outcomes of surgical treatment of
acetabular fractures in patients aged > 55 years. An initial search identified
1564 studies. After exclusion by two independent reviewers, 15 studies met the
inclusion criteria. All studies were case series and the mean Coleman Methodology
score for methodological quality assessment was 43.7 (standard deviation 12.3).
There were 354 patients with acetabular fractures. Pooled analysis revealed a
mean age of 71.6 years (55 to 96) and a mean follow-up of 43 months (20 to 188).
Complex fractures were reported in 70.1% of patients.Seven studies presented the
results of open reduction and internal fixation (ORIF); in eight other studies a
total hip arthroplasty (THA), alone or combined with different internal fixation
techniques, was the chosen treatment. In the ORIF sub-group, conversion to THA
was performed at a mean of 25.5 months with anatomical reduction in 11.6% and
imperfect and poor reduction in 22.3%. In the THA sub-group, an acetabular ring
or cage with a cemented acetabular component was used in four studies (52
patients) and a cementless acetabular component was implanted in five studies (78
patients). Six patients (4.9%) underwent revision at a mean of 39 months after
the index procedure.The analysis of intra-operative and post-operative parameters
showed a statistical difference between the two sub-groups with regards to the
mean operating time (236 mins ORIF vs 178 mins THA), the mean blood loss (707 mL
ORIF vs 974 mL THA) and the mean mortality rate at one year (22.6% ORIF vs 8.8%
THA).Based on the current data available, acute THA (alone or in combination with
internal fixation) may have a role in the treatment of older patients with
complex acetabular fractures. Despite the wide heterogenecity of fracture types
and patient co-morbidities, THA procedures were associated with lower rates of
mortality and further surgery when compared with the ORIF procedures. Cite this
article: EFORT Open Rev 2017;2:97-103. DOI: 10.1302/2058-5241.2.160036.
PMID- 28507784
TI - Geraniin attenuates naloxone-precipitated morphine withdrawal and morphine
induced tolerance in mice.
AB - BACKGROUND AND AIM: Potentially life-threatening and unpleasant side effects
associated with some analgesics have fueled the drive for the search for more
analgesics with better side effect profiles. Geraniin, the most dominant
secondary metabolite in the aqueous extract of the aerial parts of Phyllanthus
muellerianus, has been shown to possess antinociceptive properties mediated
partly by opioidergic mechanisms. The purpose of this study is to determine
whether geraniin exhibits tolerance and if it is able to ameliorate withdrawal
signs in naloxone-precipitated morphine withdrawal. MATERIALS AND METHODS: After
chronic treatment of mice with geraniin orally, the formalin test was used to
ascertain whether tolerance will develop to its antinociceptive effects and if
there is morphine-induced tolerance cross-generalization with geraniin. The
effect of geraniin on naloxone-precipitated morphine withdrawal signs in morphine
dependent mice was also investigated. RESULTS: Geraniin (3-30 mg/kg) did not
produce any tolerant effects after chronic administration and there was also no
cross-generalization with the tolerant effects of morphine. Geraniin did not
induce withdrawal signs but significantly reduced the number of jumps in morphine
dependent mice. CONCLUSION: Geraniin does not produce any tolerant effects like
morphine and also reduced the signs associated with naloxone-precipitated
morphine withdrawal in mice.
PMID- 28507783
TI - Periprosthetic shoulder infection: an overview.
AB - Periprosthetic shoulder infection (PSI) is rare but potentially devastating. The
rate of PSI is increased in cases of revision procedures, reverse shoulder
implants and co-morbidities. One specific type of PSI is the occurrence of low
grade infections caused by non-suppurative bacteria such as Propionibacterium
acnes or Staphylococcus epidemermidis.Success of treatment depends on micro
organism identification, appropriate surgical procedures and antibiotic
administration efficiency. Post-operative early PSI can be treated with simple
debridement, while chronic PSI requires a one- or two-stage revision procedure.
Indication for one-time exchange is based on pre-operative identification of a
causative agent. Resection arthroplasty remains an option for low-demand patients
or recalcitrant infection. Cite this article: EFORT Open Rev 2017;2:104-109. DOI:
10.1302/2058-5241.2.160023.
PMID- 28507786
TI - Application of Hyperosmotic Nanoemulsions in Wound Healing: Partial Thickness
Injury Model in Swine.
AB - Objective: In this work, we introduce a novel hyperosmotic nanoemulsion (HNE)
topical agent for use in wound healing. These topical emulsion complexes combine
a lipophilic thymol nanoemulsion with a hyperosmotic saccharide matrix. This
combination has been previously shown to possess synergistic antimicrobial
activity against a host of common and drug-resistant pathogens in vitro.
Approach: In this study, we present additional data to assess the safety and
efficacy of these emulsions in a partial thickness injury model in swine. Ten
wounds sized 2 * 3.5 cm were created in 18 pigs using an electrodermatome set at
a depth of 0.76 mm. The wounds were subsequently contaminated with a cocktail of
Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, and Candida
albicans at 5 * 107 total colony forming unit per wound. Treatments were
subdivided in the control group and emulsion concentrations at 0.0%, 0.01%,
0.03%, and 0.063% thymol content. Longitudinal metrics for wound healing included
rate of reepithelialization, wound bed color measurements, amount of wound
exudate, wound swab culture data, and histological examination at 4, 7, and 14
days. The cosmetics of the healed wound were obtained at day 14 with three
dimensional photogrammetry. Results: Experimental results showed that HNE reduced
the wound level bacteria count by ~0.5-1 log versus controls after 24 h. The
amount of pathogen reduction was weakly correlated to the concentration of the
emulsion. In addition, all HNE groups maintained a moist wound environment and
showed increased fibrin formation and improved hemostatic response. Innovation:
No significant difference in the rate of reepithelialization or wound closure was
found between treatment concentrations and control groups. HNE treatment did not
demonstrate any adverse host tissue response. Conclusion: These results suggest
HNE may be a candidate for reducing wound bacterial counts without compromising
reepithelialization.
PMID- 28507785
TI - A Retrospective Chart Review of Chronic Wound Patients Treated with Topical
Oxygen Therapy.
AB - Objective: Topical oxygen devices are Food and Drug Administration (FDA) cleared
for the following indications for use of various etiologies: skin ulcerations due
to diabetes, venous stasis, postsurgical infections and gangrenous lesions,
decubitus ulcers; amputations/infected stumps; skin grafts; burns; and frostbite.
The goal of this study was to understand the impact of topical oxygen therapy
(TOT) on patient outcomes, including amputation and healing rates. Approach: This
retrospective chart review included records collected between January 1, 2007,
and July 18, 2016, from male and female patients ranging in age from 4 years to
105 years. All wounds were at least 1 cm2 and were treated with at least one
separate modality before treatment with TOT and then treated with TOT for a
minimum of 2 weeks in compliance with the FDA-approved indications. All records
were from wounds that were no longer being treated with TOT. Results: In this
study, TOT was associated with an overall rate of 59.4% for a reduction in
chronic wound size, while 41.6% of wounds had no healing. The overall amputation
rate was 2.4% for wounds in this study. Innovation: To our knowledge, this
retrospective chart review represents one of the largest data sets (4,127 total
wounds) collected over one of the longest time periods (9.5 years) to evaluate
patient outcomes following TOT. Conclusion: This study revealed healing and
amputation rates similar to those reported in controlled clinical studies using
TOT to treat chronic wounds.
PMID- 28507787
TI - The Feasibility of a Handheld Electrospinning Device for the Application of
Nanofibrous Wound Dressings.
AB - Objectives: The aim of this study was to determine the feasibility of a portable
electrospinning device for the application of wound dressings. Approach: Four
polymer nanofibers dressings were applied on superficial partial thickness wounds
to a porcine model and compared with a traditional paraffin tulle gras dressing.
The polymer nanofibrous dressings were applied using a handheld portable
electrospinning device activated at a short distance from the wound. The partial
thickness donor sites were evaluated on day 2, 7, and 14 when dressings were
removed and tissue samples were taken for histological examination. Results: No
significant difference was detected between the different electrospun nanofibrous
dressings and traditional paraffin tulle gras. Desirable characteristics of the
electrospun nanofiber dressing group included nontouch technique, ease of
application, adherence and reduction in wound edema and inflammation. There was
no delayed wound healing or signs of infection reported in both the electrospun
nanofiber and traditional tulle gras dressings. Innovation: Used on partial
thickness wounds, polymer electrospun nanofiber dressings provide excellent
surface topography and are a nontouch, feasible, and safe method to promote wound
healing with the potential to reduce wound infections. Such custom-made
nanofibrous dressings have implications for the reduction of pain and trauma,
number of dressing changes, scarring, and an added cost benefit. Conclusion: We
have demonstrated that this portable handheld electrospinning device can be
utilized for different formulations and materials and customized according to the
characteristics of the target wound at the various stages of wound healing.
PMID- 28507788
TI - Adaptive T cell responses induced by oncolytic Herpes Simplex Virus-granulocyte
macrophage-colony-stimulating factor therapy expanded by dendritic cell and
cytokine-induced killer cell adoptive therapy.
AB - Purpose: Although local oncolytic viral therapy (OVT) may enhance tumor lysis,
antigen release, and adaptive immune responses, systemic antitumor responses post
therapy are limited. Adoptive immunotherapy with autologous dendritic cells (DC)
and cytokine-induced killer cells (DC-CIK) synergizes with systemic therapies. We
hypothesized that OVT with Herpes Simplex Virus-granulocyte macrophage-colony
stimulating factor (HSV-GM-CSF) would induce adaptive T cell responses that could
be expanded systemically with sequential DC-CIK therapy. Patients and Methods: We
performed a pilot study of intratumoral HSV-GM-CSF OVT followed by autologous DC
CIK cell therapy. In addition to safety and clinical endpoints, we monitored
adaptive T cell responses by quantifying T cell receptor (TCR) populations in pre
oncolytic therapy, post-oncolytic therapy, and after DC-CIK therapy. Results:
Nine patients with advanced malignancy were treated with OVT (OrienX010), of whom
seven experienced stable disease (SD). Five of the OVT treated patients underwent
leukapheresis, generation, and delivery of DC-CIKs, and two had SD, whereas three
progressed. T cell receptor sequencing of TCR beta sequences one month after OVT
therapy demonstrates a dynamic TCR repertoire in response to OVT therapy in the
majority of patients with the systematic expansion of multiple T cell clone
populations following DC-CIK therapy. This treatment was well tolerated and long
term event free and overall survival was observed in six of the nine patients.
Conclusions: Strategies inducing the local activation of tumor-specific immune
responses can be combined with adoptive cellular therapies to expand the adaptive
T cell responses systemically and further studies are warranted.
PMID- 28507789
TI - Calreticulin promotes immunity and type I interferon-dependent survival in mice
with acute myeloid leukemia.
AB - Exposure of cancer cells to particular chemotherapeutic agents or gamma
irradiation induces a form of cell death that stimulates an immune response in
mice. This "immunogenic cell death" requires calreticulin (CRT) translocation to
the plasma membrane, which has been shown to promote cancer cell phagocytosis.
However, it remains unclear whether the effect of CRT on cancer cell phagocytosis
is alone sufficient to affect tumor immunity. Acute myeloid leukemia (AML) cells
expressing cell-surface CRT were generated in order to characterize the
mechanism(s) through which CRT activates tumor immune responses. Potent immune
mediated control or rejection of AML was observed in mice with CRT-expressing
leukemia. The "CRT effect" was ultimately T-cell dependent, but dendritic cells
(DCs), and CD8alpha+ DCs in particular, were also necessary, indicating that CRT
might act directly on these DCs. CRT-expressing AML cells were slightly more
susceptible to phagocytosis by DCs in vivo, but this effect was unlikely to
explain the potent immunity observed. CRT did not affect classical DC maturation
markers, but induced expression of type I interferon (IFN), which was critical
for its positive effect on survival. In conclusion, CRT functions as a "danger
signal" that promotes a host type I IFN response associated with the induction of
potent leukemia-specific T-cell immunity.
PMID- 28507790
TI - CD69 is a direct HIF-1alpha target gene in hypoxia as a mechanism enhancing
expression on tumor-infiltrating T lymphocytes.
AB - CD69 is an early activation marker on the surface of T lymphocytes undergoing
activation by cognate antigen. We observed intense expression of CD69 on tumor
infiltrating T-lymphocytes that reside in the hypoxic tumor microenvironment and
hypothesized that CD69 could be, at least partially, under the control of the
transcriptional hypoxia response. In line with this, human and mouse CD3
stimulated lymphocytes cultured under hypoxia (1% O2) showed increased expression
of CD69 at the protein and mRNA level. Consistent with these findings, mouse T
lymphocytes that had recently undergone hypoxia in vivo, as denoted by
pimonidazole staining, were more frequently CD69+ in the tumor and bone marrow
hypoxic tissue compartments. We found evidence for HIF-1alpha involvement both
when using T-lymphocytes from inducible HIF-1alpha-/- mice and when observing
tumor-infiltrating T-lymphocytes in mice whose T cells are HIF-1alpha-/-. Direct
pro-transcriptional activity of HIF-1alpha on a newly identified hypoxia response
element (HRE) found in the human CD69 locus was demonstrated by ChIP experiments.
These results uncover a connection between the HIF-1alpha oxygen-sensing pathway
and CD69 immunobiology.
PMID- 28507791
TI - The mutational status of p53 can influence its recognition by human T-cells.
AB - p53 was reported to be an attractive immunotherapy target because it is mutated
in approximately half of human cancers, resulting in its inactivation and often
accumulation in tumor cells. Peptides derived from p53 are presented by class I
MHC molecules and may act as tumor-associated epitopes which could be targeted by
p53-specific T cells. Interestingly, it was recently shown that there is a lack
of significant correlation between p53 expression levels in tumors and their
recognition by p53-TCR transduced T cells. To better understand the influence of
the mutational status of p53 on its presentation by the MHC system and on T cell
antitumor reactivity, we generated several mutant p53 constructs and expressed
them in HLA-A2+/p53- cells. Upon co-culture with p53-specific T cells, we
measured the specific recognition of p53-expressing target cells by means of
cytokine secretion, marker upregulation and cytotoxicity, and in parallel
determined p53 expression levels by intracellular staining. We also examined the
relevance of antigen presentation components on p53 recognition and the impact of
mutant p53 expression on cell-cycle dynamics. Our results show that selected p53
mutations altering protein stability can modulate p53 presentation to T cells,
leading to a differential immune reactivity inversely correlated with measured
p53 protein levels. Thus, p53 may behave differently than other classical tumor
antigens and its mutational status should therefore be taken into account when
elaborating immunotherapy treatments of cancer patients targeting p53.
PMID- 28507792
TI - Oncolytic measles virus encoding interleukin-12 mediates potent antitumor effects
through T cell activation.
AB - Combination of oncolytic virotherapy with immunomodulators is emerging as a
promising therapeutic strategy for numerous tumor entities. In this study, we
developed measles Schwarz vaccine strain vectors encoding immunomodulators to
support different phases in the establishment of antitumor immune responses.
Therapeutic efficacy of the novel vectors was evaluated in the immunocompetent
MC38cea tumor model. We identified vectors encoding an IL-12 fusion protein
(MeVac FmIL-12) and an antibody against PD-L1 (MeVac anti-PD-L1), respectively,
as the most effective. Treatment of established tumors with MeVac FmIL-12
achieved 90% complete remissions. Profiling of the tumor immune microenvironment
revealed activation of a type 1 T helper cell-directed response, with MeVac FmIL
12 ensuring potent early natural killer and effector T cell activation as well as
upregulation of the effector cytokines IFN-gamma and TNF-alpha. CD8+ T cells were
found to be essential for the therapeutic efficacy of MeVac FmIL-12. Results of
this study present MeVac FmIL-12 as a novel approach for targeted IL-12 delivery
and elucidate mechanisms of successful immunovirotherapy.
PMID- 28507793
TI - Composite biomarkers defined by multiparametric immunofluorescence analysis
identify ALK-positive adenocarcinoma as a potential target for immunotherapy.
AB - Anaplastic lymphoma kinase (ALK) inhibitors have been successfully developed for
non-small cell lung carcinoma (NSCLC) displaying chromosomal rearrangements of
the ALK gene, but unfortunately resistance invariably occurs. Blockade of the PD
1-PD-L1/2 inhibitory pathway constitutes a breakthrough for the treatment of
NSCLC. Some predictive biomarkers of clinical response to this therapy are
starting to emerge, such as PD-L1 expression by tumor/stromal cells and
infiltration by CD8+ T cells expressing PD-1. To more effectively integrate all
of these potential biomarkers of clinical response to immunotherapy, we have
developed a multiparametric immunofluorescence technique with automated immune
cell counting to comprehensively analyze the tumor microenvironment of ALK
positive adenocarcinoma (ADC). When analyzed as either a continuous or a
dichotomous variable, the mean number of tumor cells expressing PD-L1 (p = 0.012)
and the percentage of tumor cells expressing PD-L1 were higher in ALK-positive
ADC than in EGFR-mutated ADC or WT (non-EGFR-mutated and non-KRAS-mutated) NSCLC.
A very strong correlation between PD-L1 expression on tumor cells and
intratumoral infiltration by CD8+ T cells was observed, suggesting that an
adaptive mechanism may partly regulate this expression. A higher frequency of
tumors combining positive PD-L1 expression and infiltration by intratumoral CD8+
T cells or PD-1+CD8+ T cells was also observed in ALK-positive lung cancer
patients compared with EGFR-mutated (p = 0.03) or WT patients (p = 0.012). These
results strongly suggest that a subgroup of ALK-positive lung cancer patients may
constitute good candidates for anti-PD-1/-PD-L1 therapies.
PMID- 28507794
TI - A novel nanobody-based target module for retargeting of T lymphocytes to EGFR
expressing cancer cells via the modular UniCAR platform.
AB - Recent treatments of leukemias with chimeric antigen receptor (CAR) expressing T
cells underline their impressive therapeutic potential. However, once adoptively
transferred into patients, there is little scope left to shut them down after
elimination of tumor cells or in case adverse side effects occur. This becomes of
special relevance if they are directed against commonly expressed tumor
associated antigens (TAAs) such as receptors of the ErbB family. To overcome this
limitation, we recently established a modular CAR platform technology termed
UniCAR. UniCARs are not directed against TAAs but instead against a unique
peptide epitope on engineered recombinant targeting modules (TMs), which guide
them to the target. In the absence of a TM UniCAR T cells are inactive. Thus an
interruption of any UniCAR activity requires an elimination of unbound TM and the
TM complexed with UniCAR T cells. Elimination of the latter one requires a
disassembly of the UniCAR-TM complexes. Here, we describe a first nanobody (nb)
based TM directed against EGFR. The novel TM efficiently retargets UniCAR T cells
to EGFR positive tumors and mediates highly efficient target-specific and target
dependent tumor cell lysis both in vitro and in vivo. After radiolabeling of the
novel TM with 64Cu and 68Ga, we analyzed its biodistribution and clearance as
well as the stability of the UniCAR-TM complexes. As expected unbound TM is
rapidly eliminated while the elimination of the TM complexed with UniCAR T cells
is delayed. Nonetheless, we show that UniCAR-TM complexes dissociate in vitro and
in vivo in a concentration-dependent manner in line with the concept of a
repeated stop and go retargeting of tumor cells via the UniCAR technology.
PMID- 28507796
TI - LYG1 exerts antitumor function through promoting the activation, proliferation,
and function of CD4+ T cells.
AB - Identification of novel stimulatory cytokines with antitumor function would have
great value in tumor immunotherapy investigations. Here, we report LYG1 (Lysozyme
G-like 1) identified through the strategy of Immunogenomics as a novel classical
secretory protein with tumor-inhibiting function. LYG1 recombinant protein
(rhLYG1) could significantly suppress the growth of B16 tumors in WT B6 mice, but
not in SCID-beige mice, Rag1-/- mice, CD4+- or CD8+ T cell-deleted mice. It could
increase the number of CD4+ and CD8+ T cells in tumor-infiltrating lymphocytes,
tumor-draining lymph nodes, and spleens, and promote IFNgamma production by T
cells in tumor-bearing mice. In vitro experiments demonstrated that rhLYG1 could
directly enhance IFNgamma secretion by CD4+ T cells, but not CD8+ T cells.
Moreover, it could promote the activation, proliferation, and IFNgamma production
of tumor antigen-specific CD4+ T cells. The tumor-inhibiting effect of LYG1 was
eliminated in Ifng-/- mice. Furthermore, LYG1 deficiency accelerated B16 and LLC1
tumor growth and inhibited the function of T cells. In summary, our findings
reveal a tumor-inhibiting role for LYG1 through promoting the activation,
proliferation, and function of CD4+ T cells in antitumor immune responses,
offering implications for novel tumor immunotherapy.
PMID- 28507795
TI - Digital analysis and epigenetic regulation of the signature of rejection in
colorectal cancer.
AB - The immune system plays a pivotal role in the development and progression of
colorectal cancer (CRC). Tumor immune rejection has been previously linked to the
activation of the interferon-stimulated genes (ISG) STAT1, IRF-5 and IRF-1.
Specific immunoregulatory microRNAs (miRNAs) may impact the expression of these
ISG in the tumor microenvironment. In this translational study, we develop a
digital image analysis protocol to identify the ISG-gene expression signature and
investigate miRNA expression in the immediate environment of invading cancer
cells. Digital immunophenotyping was performed using next generation tissue
microarrays from 241 well-characterized CRC patients and analyzed with
clinicopathological and molecular information. Active ISG signaling in the tumor
stroma differentiated an immune-activated (n = 178) and a quiescent (n = 43)
phenotype. The activated phenotype was associated with high counts of
intratumoral CD8+ cytotoxic T-lymphocytes (CTL; p = 0.007) and expression of the
immune effector molecules granzyme B (p < 0.001) and perforin (p = 0.020). Immune
activated tumors also showed an elevated expression of the intercellular adhesion
molecule-1 (ICAM-1, p = 0.006) which may facilitate CTL infiltration. Patients
with immune-activated CRC had a considerably reduced risk of developing distant
metastases (p = 0.001, OR = 0.034, 95%CI = 0.006-0.183). High expression of the
immunoregulatory miR-34a and miR-93 corresponded to a 2-2.5-fold decrease of
STAT1 (p = 0.006) and IRF-1 (p = 0.058), a feature more commonly seen in a
quiescent microenvironment. Analysis of a combined ISG marker profile by digital
pathology stratifies CRC patients into diametrically opposed immune phenotypes.
Targeted inhibition of miRNAs within the tumor microenvironment may form a new
strategy to stimulate the anti-tumoral immune response.
PMID- 28507797
TI - IL15 induces a potent antitumor activity in NK cells isolated from malignant
pleural effusions and overcomes the inhibitory effect of pleural fluid.
AB - Natural Killer (NK) cells are capable of recognizing and killing cancer cells and
play an important role in tumor immunosurveillance. However, tumor-infiltrating
NK cells are frequently impaired in their functional capability. A remarkable
exception is represented by NK cells isolated from malignant pleural effusions
(PE) that are not anergic and, upon IL2-induced activation, efficiently kill
tumor cells. Although IL2 is used in various clinical trials, severe side effects
may occur in treated patients. In this study, we investigated whether also other
clinical-grade cytokines could induce strong cytotoxicity in NK cells isolated
from pleural fluid of patients with primary or metastatic tumors of different
origins. We show that PE-NK cells, cultured for short-time intervals with IL15,
maintain the CD56bright phenotype, a high expression of the main activating
receptors, produce cytokines and kill tumor cells in vitro similarly to those
treated with IL2. Moreover, IL15-activated PE-NK cells could greatly reduce the
growth of established tumors in mice. This in vivo antitumor effect correlated
with the ability of IL15-activated PE-NK cells to traffic from periphery to the
tumor site. Finally, we show that IL15 can counteract the inhibitory effect of
the tumor pleural microenvironment. Our study suggests that IL15-activated NK
cells isolated from pleural fluid (otherwise discarded after thoracentesis) may
represent a suitable source of effector cells to be used in adoptive
immunotherapy of cancer.
PMID- 28507798
TI - Tumor-infiltrating neutrophils predict benefit from adjuvant chemotherapy in
patients with muscle invasive bladder cancer.
AB - Growing evidence shows tumor-infiltrating neutrophils (TINs) involvement in
tumorigenesis. The objective of this study is to assess the prognostic effect of
TINs and its impact on adjuvant chemotherapy benefits in muscle invasive bladder
cancer (MIBC). A total of 142 MIBC patients from Zhongshan Hospital, 119 MIBC
patients from FUSCC, and 405 MIBC patients from TCGA cohort were enrolled in the
study. TINs were evaluated by immunohistochemical staining of CD66b or the
CIBERSORT method. Patients with high TINs had a significantly poorer overall
survival (p = 0.001, p < 0.001, and p = 0.002, respectively) in the three sets.
In the multivariate analysis, the presence of high TINs (HR = 2.122, p = 0.007;
HR = 3.807, p < 0.001; HR = 2.104, p = 0.001; respectively) was identified as an
independent prognostic factor for overall survival in the three sets. More
importantly, Low TINs patients had significantly longer overall survival in
patients without ACT in the three sets. Gene set enrichment analysis showed that
lymphocyte activation (p < 0.001) and T cell activation (p = 0.008) were
significantly enriched in the low TINs group. In addition, TINs were negatively
correlated with CD8+ T cells, suggesting that the status of high-TINs was linked
to the status of immunosuppression in MIBC. TINs could be used as independent
prognostic factor. Low TINs identified a subgroup of MIBC patients who appeared
to benefit from adjuvant chemotherapy. Incorporation of TINs into TNM system
could further stratify patients with different prognosis.
PMID- 28507799
TI - Characterization of a human anti-tumoral NK cell population expanded after BCG
treatment of leukocytes.
AB - Immunotherapy, via intra-vesical instillations of BCG, is the therapy of choice
for patients with high-risk non-muscle invasive bladder cancer. The subsequent
recruitment of lymphocytes and myeloid cells, as well as the release of cytokines
and chemokines, is believed to induce a local immune response that eliminates
these tumors, but the detailed mechanisms of action of this therapy are not well
understood. Here, we have studied the phenotype and function of the responding
lymphocyte populations as well as the spectrum of cytokines and chemokines
produced in an in vitro model of human peripheral blood mononuclear cells (PBMCs)
co-cultured with BCG. Natural killer (NK) cell activation was a prominent feature
of this immune response and we have studied the expansion of this lymphocyte
population in detail. We show that, after BCG stimulation, CD56dim NK cells
proliferate, upregulate CD56, but maintain the expression of CD16 and the ability
to mediate ADCC. CD56bright NK cells also contribute to this expansion by
increasing CD16 and KIR expression. These unconventional CD56bright cells
efficiently degranulated against bladder cancer cells and the expansion of this
population required the release of soluble factors by other immune cells in the
context of BCG. Consistent with these in vitro data, a small, but significant
increase in the intensity of CD16 expression was noted in peripheral blood
CD56bright cells from bladder cancer patients undergoing BCG therapy, that was
not observed in patients treated with mitomycin-C instillations. These
observations suggest that activation of NK cells may be an important component of
the anti-tumoral immune response triggered by BCG therapy in bladder cancer.
PMID- 28507800
TI - Formyl peptide receptor 1 suppresses gastric cancer angiogenesis and growth by
exploiting inflammation resolution pathways.
AB - Chronic inflammation can result from inadequate engagement of resolution
mechanisms, mainly accomplished by specialized pro-resolving mediators (SPMs)
arising from the metabolic activity of lipoxygenases (ALOX5/15) on omega-6 or
omega-3 essential polyunsaturated fatty acids (PUFA). We previously demonstrated
that formyl peptide receptor 1 (FPR1) suppresses gastric cancer (GC) by
inhibiting its inflammatory/angiogenic potential. In this study, we asked whether
FPR1 exploits inflammation resolution pathways to suppress GC angiogenesis and
growth. Here, we demonstrate that genetic or pharmacologic modulation of FPR1 in
GC cells regulated ALOX5/15 expression and production of the SPMs Resolvin D1
(RvD1) and Lipoxin B4 (LXB4). SPM treatment of GC cells abated their angiogenic
potential. Genetic deletion of ALOX15 or of the RvD1 receptor GPR32 increased the
angiogenic and tumorigenic activity of GC cells thereby mimicking FPR1 loss.
Deletion/inhibition of ALOX5/15 or GPR32 blocked FPR1-mediated anti-angiogenic
activities, indicating that ALOX5/15 and GPR32 are required for FPR1's pro
resolving action. An omega-3- or omega-6-enriched diet enforced SPM endogenous
production in mice and inhibited growth of shFPR1 GC xenografts by suppressing
their angiogenic activity. These data implicate that FPR1 and/or pro-resolving
pathway components might be used as risk/prognostic markers for GC; omega-6/3
enriched diets, and targeting FPR1 or SPM machinery may be exploited for GC
management.
PMID- 28507801
TI - The novel negative checkpoint regulator VISTA is expressed in gastric carcinoma
and associated with PD-L1/PD-1: A future perspective for a combined gastric
cancer therapy?
AB - A combined blockade of V-domain Ig suppressor of T-cell activation (VISTA) and PD
1 is a promising new cancer treatment option, which was efficient in murine tumor
models and is currently tested in first phase I studies. Here, we analyzed the
VISTA expression in a large and well-characterized gastric cancer (GC) cohort on
464 therapy-naive GC samples and 14 corresponding liver metastases using
immunohistochemistry. Staining results were correlated with clinico-pathological
characteristics, genetic alterations and survival. VISTA expression in tumor
cells was detected in 41 GCs (8.8%) and 2 corresponding liver metastases (14.3%).
Moreover, VISTA expression in immune cells was observed in 388 GCs (83.6%) and 6
liver metastases (42.9%). VISTA expression was associated with the Lauren
phenotype, tumor localization, Epstein-Barr virus infection, KRAS- and PIK3CA
mutational status and PD-L1 expression. There was no significant correlation with
patient outcome. Moreover, a change of VISTA expression in immune cells during
tumor progression was observed. The co-incidence of VISTA and PD-L1 expression
indicates a dual immune evasion mechanism of GC tumor cells and makes GC an
interesting target for novel combined immune checkpoint inhibitor treatments.
PMID- 28507803
TI - PD-L1 expression on malignant cells is no prerequisite for checkpoint therapy.
AB - Immunotherapy with PD-1/PD-L1-blocking antibodies is clinically effective for
several tumor types, but the mechanism is not fully understood. PD-L1 expression
on tumor biopsies is generally regarded as an inclusion criterion for this cancer
therapy. Here, we describe the PD-L1-blocking therapeutic responses of
preclinical tumors in which PD-L1 expression was removed from cancer cells, but
not from immune infiltrate. Lack of PD-L1 expression on malignant cells delayed
tumor outgrowth in a CD8+ T cell-mediated fashion, showing the importance of this
molecule in immune suppression. PD-L1 expression was evident on myeloid
infiltrating cells in the microenvironment of these tumors and targeting stromal
PD-L1 with blocking antibody therapy had additional antitumor effect,
demonstrating that PD-L1 on both malignant cells and immune cells is involved in
the mechanism of immunotherapeutic antibodies. Importantly, comparable results
were obtained with PD-1-blocking therapy. These findings have implications for
inclusion of cancer patients in PD-1/PD-L1 blockade immunotherapies.
PMID- 28507804
TI - HLA dependent immune escape mechanisms in B-cell lymphomas: Implications for
immune checkpoint inhibitor therapy?
AB - Antigen presentation by tumor cells in the context of Human Leukocyte Antigen
(HLA) is generally considered to be a prerequisite for effective immune
checkpoint inhibitor therapy. We evaluated cell surface HLA class I, HLA class II
and cytoplasmic HLA-DM staining by immunohistochemistry (IHC) in 389 classical
Hodgkin lymphomas (cHL), 22 nodular lymphocyte predominant Hodgkin lymphomas
(NLPHL), 137 diffuse large B-cell lymphomas (DLBCL), 39 primary central nervous
system lymphomas (PCNSL) and 19 testicular lymphomas. We describe a novel
mechanism of immune escape in which loss of HLA-DM expression results in aberrant
membranous invariant chain peptide (CLIP) expression in HLA class II cell surface
positive lymphoma cells, preventing presentation of antigenic peptides. In HLA
class II positive cases, HLA-DM expression was lost in 49% of cHL, 0% of NLPHL,
14% of DLBCL, 3% of PCNSL and 0% of testicular lymphomas. Considering HLA class
I, HLA class II and HLA-DM together, 88% of cHL, 10% of NLPHL, 62% of DLBCL, 77%
of PCNSL and 87% of testicular lymphoma cases had abnormal HLA expression
patterns. In conclusion, an HLA expression pattern incompatible with normal
antigen presentation is common in cHL, DLBCL, PCNSL and testicular lymphoma.
Retention of CLIP in HLA class II caused by loss of HLA-DM is a novel immune
escape mechanism, especially prevalent in cHL. Aberrant HLA expression should be
taken into account when evaluating efficacy of checkpoint inhibitors in B-cell
lymphomas.
PMID- 28507802
TI - B cells and the humoral response in melanoma: The overlooked players of the tumor
microenvironment.
AB - Evidence of tumor-resident mature B cell and antibody compartments and reports of
associations with favorable prognosis in malignant melanoma suggest that humoral
immunity could participate in antitumor defense. Likely striving to confer
immunological protection while being subjected to tumor-promoting immune
tolerance, B cells may engender multiple functions, including antigen processing
and presentation, cytokine-mediated signaling, antibody class switching,
expression and secretion. We review key evidence in support of multifaceted
immunological mechanisms by which B cells may counter or contribute to malignant
melanoma, and we discuss their potential translational implications. Dissecting
the contributions of tumor-associated humoral responses can inform future
treatment avenues.
PMID- 28507805
TI - Generation and functional characterization of MDSC-like cells.
AB - Myeloid-derived suppressor cells (MDSC) are critical in regulating immune
responses by suppressing antigen presenting cells (APC) and T cells. We
previously observed that incubation of peripheral blood monocytes with
interleukin (IL)-10 during their differentiation to monocyte-derived dendritic
cells (moDCs) results in the generation of an APC population with a CD14+HLA
DRlowphenotype (IL-10-APC) with reduced stimulatory capacity similar to human
MDSC. Co-incubation experiments now revealed that the addition of IL-10-APC to
moDC caused a reduction of DC-induced T-cell proliferation, of the expression of
maturation markers, and of secreted cytokines and chemokines such as TNF-alpha,
IL-6, MIP-1alpha and Rantes. Addition of IL-10-APC increased the
immunosuppressive molecule osteoactivin and its corresponding receptor syndecan-4
on moDC. Moreover, CD14+HLA-DRlow MDSC isolated from healthy donors expressed
high levels of osteoactivin, which was even further upregulated by the auxiliary
addition of IL-10. Using transcriptome analysis, we identified a set of molecules
and pathways mediating these effects. In addition, we found that IL-10-APC as
well as human isolated MDSC expressed higher levels of programmed death (PD)-1,
PD-ligand-1 (PD-L1), glucocorticoid-induced-tumor-necrosis-factor-receptor
related-protein (GITR) and GITR-ligand. Inhibition of osteoactivin, syndecan-4,
PD-1 or PD-L1 on MDSC by using blocking antibodies restored the stimulatory
capacity of DC in co-incubation experiments. Activation of MDSC with Dectin-1
ligand curdlan reduced the expression of osteoactivin and PD-L1. Our results
demonstrate that osteoactivin/syndecan-4 and PD-/PD-L1 are key molecules that are
profoundly involved in the inhibitory effects of MDSC on DC function and might be
promising tools for clinical application.
PMID- 28507807
TI - Host antitumor resistance improved by the macrophage polarization in a chimera
model of patients with HCC.
AB - Despite major advances in curative and palliative approaches, hepatocellular
carcinoma (HCC) is still the third leading cause of cancer-related death
worldwide. M1 macrophages (Mphi) play a key role in host antitumor defenses in
HCC. In our study, CD14+ cells were isolated from the peripheral blood of four
groups of HCC patients (group-1, patients with stage 0 HCC; group-2, patients
with stage A HCC; group-3, patients with stage B HCC; and group-4, patients with
stage C HCC) and characterized phenotypically. Then, CD14+ cells from group-2 and
group-3 HCC patients were induced to polarize and tested for their antitumor
abilities in a chimera model of HCC patients. Human HCCs (HepG2 solid tumors)
grew in a chimera model of group-3 patients (group-3 HCC chimeras) but not in a
chimera model of group-2 patients (group-2 HCC chimeras). In response to HCC
antigens, the majority of CD14+ cells from group-2 patients (group-2 CD14+ cells)
switched to the M1 phenotype (IL-12+IL-10-iNOS+cells), whereas the majority of
CD14+ cells from group-3 patients (group-3 CD14+ cells) did not switch to the M1
phenotype and continued to express M2b phenotypic properties (IL-12-IL
10+CCL1+iNOS-cells). Group-3 CD14+ cells showed M1Mphi polarization after
treatment with CCL1 antisense oligodeoxynucleotide (ODN). Therefore, our study
indicates that anti-HCC defenses of group-3 HCC chimeras are improved after CCL1
antisense ODN treatment.
PMID- 28507806
TI - Preclinical efficacy of immune-checkpoint monotherapy does not recapitulate
corresponding biomarkers-based clinical predictions in glioblastoma.
AB - Glioblastoma (GBM) is resistant to most multimodal therapies. Clinical success of
immune-checkpoint inhibitors (ICIs) has spurred interest in applying ICIs
targeting CTLA4, PD1 or IDO1 against GBM. This amplifies the need to ascertain
GBM's intrinsic susceptibility (or resistance) toward these ICIs, through
clinical biomarkers that may also "guide and prioritize" preclinical testing.
Here, we interrogated the TCGA and/or REMBRANDT human patient-cohorts to predict
GBM's predisposition toward ICIs. We exploited various broad clinical biomarkers,
including mutational or predicted-neoantigen burden, pre-existing or basal levels
of tumor-infiltrating T lymphocytes (TILs), differential expression of immune
checkpoints within the tumor and their correlation with particular TILs/Treg
associated functional signature and prognostic impact of differential immune
checkpoint expression. Based on these analyses, we found that predictive
biomarkers of ICI responsiveness exhibited inconsistent patterns in GBM patients,
i.e., they either predicted ICI resistance (as compared with typical ICI
responsive cancer-types like melanoma, lung cancer or bladder cancer) or
susceptibility to therapeutic targeting of CTLA4 or IDO1. On the other hand, our
comprehensive literature meta-analysis and preclinical testing of ICIs using an
orthotopic GL261-glioma mice model, indicated significant antitumor properties of
anti-PD1 antibody, whereas blockade of IDO1 or CTLA4 either failed or provided
very marginal advantage. These trends raise the need to better assess the
applicability of ICIs and associated biomarkers for GBM.
PMID- 28507808
TI - Pro-necrotic molecules impact local immunosurveillance in human breast cancer.
AB - Necrosis culminates in spilling cellular content through the permeabilized plasma
membrane, thereby releasing potentially immunostimulatory molecules in the
pericellular space of dead cells. Accordingly, molecules involved in necroptotic
signaling, such as receptor-interacting serine/threonine-protein kinase 3 (RIPK3)
and mixed lineage kinase-like (MLKL) have been found to stimulate anticancer
immune responses in mouse models of chemotherapy. mRNAs encoding prominent pro
necrotic gene products (RIPK1, RIPK3, MLKL, PGAM5 and DFNA5) were correlated with
immune-related metagenes in several cancer types (breast, colorectal, lung,
ovary, melanoma), revealing the strongest associations in breast cancer. In two
independent breast cancer cohorts, the expression of MLKL and DFNA5 was decreased
at the mRNA levels in tumor as compared with normal tissues. Moreover, MLKL
expression exhibited a strong positive correlation with genes reflecting the
presence of B, NK and T lymphocytes in the tumor bed, in multiple distinct breast
cancer subtypes. In contrast, the positive correlation between RIPK3 and lymphoid
cells was restricted to HER2+ and triple negative/basal-like breast cancer.
Moreover, the expression of DFNA5, which mediates post-apoptotic secondary
necrosis, mostly correlated with the monocytic lineage and macrophages in
ER+/luminal A breast cancers. MLKL (and to some extent RIPK1 and RIPK3) was
strongly associated with the local expression of genes involved in interferon
alpha and interferon-gamma responses. Altogether, these results support the idea
that pro-necrotic signaling facilitates intratumoral immune responses in human
breast cancer.
PMID- 28507810
TI - TIE-2 expressing monocytes in human cancers.
AB - Tumor-associated macrophages (TAM) are well known as a key player in the tumor
microenvironment, which support cancer progression. More recently, a lineage of
monocytes characterized by the expression of the TIE-2/Tek angiopoietin receptor
identified a subset of circulating and tumor-associated monocytes endowed with
proangiogenic activity. TIE-2 expressing monocytes (TEM) were found both in
humans and mice. Here, we review the phenotypes and functions of TEM reported so
far in human cancer and their potential use as markers of cancer progression and
metastasis. Finally, we discuss the therapeutic approaches currently used or
proposed to target TEM.
PMID- 28507809
TI - T cell therapy targeting a public neoantigen in microsatellite instable colon
cancer reduces in vivo tumor growth.
AB - T-cell receptor (TCR) transfer is an attractive strategy to increase the number
of cancer-specific T cells in adoptive cell therapy. However, recent clinical and
pre-clinical findings indicate that careful consideration of the target antigen
is required to limit the risk of off-target toxicity. Directing T cells against
mutated proteins such as frequently occurring frameshift mutations may thus be a
safer alternative to tumor-associated self-antigens. Furthermore, such frameshift
mutations result in novel polypeptides allowing selection of TCRs from the non
tolerant T-cell repertoire circumventing the problem of low affinity TCRs due to
central tolerance. The transforming growth factor beta Receptor II frameshift
mutation (TGFbetaRIImut) is found in Lynch syndrome cancer patients and in
approximately 15% of sporadic colorectal and gastric cancers displaying
microsatellite instability (MSI). The -1A mutation within a stretch of 10 adenine
bases (nucleotides 709-718) of the TGFbetaRII gene gives rise to immunogenic
peptides previously used for vaccination of MSI+ colorectal cancer patients in a
Phase I clinical trial. From a clinically responding patient, we isolated a
cytotoxic T lymphocyte (CTL) clone showing a restriction for HLA-A2 in complex
with TGFbetaRIImut peptide. Its TCR was identified and shown to redirect T cells
against colon carcinoma cell lines harboring the frameshift mutation. Finally, T
cells transduced with the HLA-A2-restricted TGFbetaRIImut-specific TCR were
demonstrated to significantly reduce the growth of colorectal cancer and enhance
survival in a NOD/SCID xenograft mouse model.
PMID- 28507811
TI - Adoptive natural killer cell therapy is effective in reducing pulmonary
metastasis of Ewing sarcoma.
AB - The survival of patients with metastatic or relapsed Ewing sarcoma (ES) remains
dismal despite intensification of combination chemotherapy and radiotherapy,
precipitating the need for novel alternative therapies with minimal side effects.
Natural killer (NK) cells are promising additions to the field of cellular
immunotherapy. Adoptive NK cell therapy has shown encouraging results in
hematological malignancies. Despite these initial promising successes, however,
NK cell therapy for solid tumors remains to be investigated using in vivo tumor
models. The purpose of this study is to evaluate the efficacy of ex vivo expanded
human NK cells in controlling primary and metastatic ES tumor growth in vitro and
in vivo. Using membrane-bound IL-21 containing K562 (K562-mbIL-21) expansion
platform, we were able to obtain sufficient numbers of expanded NK (eNK) cells
that display favorable activation phenotypes and inflammatory cytokine secretion,
along with a strong in vitro cytotoxic effect against ES. Furthermore, eNK
therapy significantly decreased lung metastasis without any significant
therapeutic effect in limiting primary tumor growth in an in vivo xenograft
model. Our data demonstrate that eNK may be effective against pulmonary
metastatic ES, but challenges remain to direct proper trafficking and augmenting
the cytotoxic function of eNK to target primary tumor sites.
PMID- 28507812
TI - A BARF1-specific mAb as a new immunotherapeutic tool for the management of EBV
related tumors.
AB - The use of monoclonal antibodies (mAb) for the diagnosis and treatment of
malignancies is acquiring an increasing clinical importance, thanks to their
specificity, efficacy and relative easiness of use. However, in the context of
Epstein-Barr virus (EBV)-related malignancies, only cancers of B-cell origin can
benefit from therapeutic mAb targeting specific B-cell lineage antigens. To
overcome this limitation, we generated a new mAb specific for BARF1, an EBV
encoded protein with transforming and immune-modulating properties. BARF1 is
expressed as a latent protein in nasopharyngeal (NPC) and gastric carcinoma (GC),
and also in neoplastic B cells mainly upon lytic cycle induction, thus
representing a potential target for all EBV-related malignancies. Considering
that BARF1 is largely but not exclusively secreted, the BARF1 mAb was selected on
the basis of its ability to bind a domain of the protein retained at the cell
surface of tumor cells. In vitro, the newly generated mAb recognized the target
molecule in its native conformation, and was highly effective in mediating both
ADCC and CDC against BARF1-positive tumor cells. In vivo, biodistribution
analysis in mice engrafted with BARF1-positive and -negative tumor cells
confirmed its high specificity for the target. More importantly, the mAb
disclosed a relevant antitumor potential in preclinical models of NPC and
lymphoma, as evaluated in terms of both reduction of tumor masses and long-term
survival. Taken together, these data not only confirm BARF1 as a promising target
for immunotherapeutic interventions, but also pave the way for a successful
translation of this new mAb to the clinical use.
PMID- 28507814
TI - Erratum.
AB - [This corrects the article DOI: 10.1080/2162402X.2016.1249558.].
PMID- 28507813
TI - Deep exploration of the immune infiltrate and outcome prediction in testicular
cancer by quantitative multiplexed immunohistochemistry and gene expression
profiling.
AB - Platinum-based chemotherapy is usually curative for patients with testicular germ
cell tumors (TGCT), but a subset of patients experience disease progression and
poor clinical outcomes. Here, we tested whether immune profiling of TGCT could
identify novel prognostic markers and therapeutic targets for this patient
cohort. We obtained primary and metastatic TGCT samples from one center. We
performed immune profiling using multiplexed fluorescence immunohistochemistry
(FIHC) for T-cell subsets and immune checkpoints, and targeted gene expression
profiling (Nanostring nCounter Immune panel). Publically available data sets were
used to validate primary sample analyses. Nearly all samples had some degree of T
cell infiltration and immune checkpoint expression. Seminomas were associated
with increased CD3+ T-cell infiltration, decreased Regulatory T-cells, increased
PD-L1, and increased PD-1/PD-L1 spatial interaction compared with non-seminomas
using FIHC. Gene expression profiling confirmed these findings and also
demonstrated increased expression of T-cell markers (e.g., IFNgamma, and LAG3)
and cancer/testis antigens (e.g., PRAME) in seminomas, whereas non-seminomas
demonstrated high neutrophil and macrophage gene signatures. Irrespective of
histology, advanced TGCT stage was associated with decreased T-cell and NK-cell
signatures, while Treg, neutrophil, mast cell and macrophage signatures increased
with advanced stage. Importantly, cancer/testis antigen, neutrophil, and
CD8+/regulatory T-cell signatures correlated with recurrence free survival. Thus,
deep immune characterization of TGCT using IHC and gene expression profiling
identified activated T-cell infiltration which correlated with seminoma histology
and good prognosis. These results may provide a rationale for testing of anti-PD
1/PD-L1 agents and suggest prognostic markers.
PMID- 28507815
TI - A new molecular diagnostic tool for surveying and monitoring Triops cancriformis
populations.
AB - The tadpole shrimp, Triops cancriformis, is a freshwater crustacean listed as
endangered in the UK and Europe living in ephemeral pools. Populations are
threatened by habitat destruction due to land development for agriculture and
increased urbanisation. Despite this, there is a lack of efficient methods for
discovering and monitoring populations. Established macroinvertebrate monitoring
methods, such as net sampling, are unsuitable given the organism's life history,
that include long lived diapausing eggs, benthic habits and ephemerally active
populations. Conventional hatching methods, such as sediment incubation, are both
time consuming and potentially confounded by bet-hedging hatching strategies of
diapausing eggs. Here we develop a new molecular diagnostic method to detect
viable egg banks of T. cancriformis, and compare its performance to two
conventional monitoring methods involving diapausing egg hatching. We apply this
method to a collection of pond sediments from the Wildfowl & Wetlands Trust
Caerlaverock National Nature Reserve, which holds one of the two remaining
British populations of T. cancriformis. DNA barcoding of isolated eggs, using
newly designed species-specific primers for a large region of mtDNA, was used to
estimate egg viability. These estimates were compared to those obtained by the
conventional methods of sediment and isolation hatching. Our method outperformed
the conventional methods, revealing six ponds holding viable T. cancriformis
diapausing egg banks in Caerlaverock. Additionally, designed species-specific
primers for a short region of mtDNA identified degraded, inviable eggs and were
used to ascertain the levels of recent mortality within an egg bank. Together
with efficient sugar flotation techniques to extract eggs from sediment samples,
our molecular method proved to be a faster and more powerful alternative for
assessing the viability and condition of T. cancriformis diapausing egg banks.
PMID- 28507816
TI - Psychophysical measurements in children: challenges, pitfalls, and
considerations.
AB - Measuring sensory sensitivity is important in studying development and
developmental disorders. However, with children, there is a need to balance
reliable but lengthy sensory tasks with the child's ability to maintain
motivation and vigilance. We used simulations to explore the problems associated
with shortening adaptive psychophysical procedures, and suggest how these
problems might be addressed. We quantify how adaptive procedures with too few
reversals can over-estimate thresholds, introduce substantial measurement error,
and make estimates of individual thresholds less reliable. The associated
measurement error also obscures group differences. Adaptive procedures with
children should therefore use as many reversals as possible, to reduce the
effects of both Type 1 and Type 2 errors. Differences in response consistency,
resulting from lapses in attention, further increase the over-estimation of
threshold. Comparisons between data from individuals who may differ in lapse rate
are therefore problematic, but measures to estimate and account for lapse rates
in analyses may mitigate this problem.
PMID- 28507817
TI - Which psychological, social and physical environmental characteristics predict
changes in physical activity and sedentary behaviors during early retirement? A
longitudinal study.
AB - BACKGROUND: In the context of healthy ageing, it is necessary to identify
opportunities to implement health interventions in order to develop an active
lifestyle with sufficient physical activity and limited sedentary time in middle
aged and older adults. The transition to retirement is such an opportunity, as
individuals tend to establish new routines at the start of retirement. Before
health interventions can be developed, the psychological, social and physical
environmental determinants of physical activity and sedentary behaviors during
early retirement should be identified, ideally with longitudinal studies. The aim
of this paper was first to examine whether psychological, social and physical
environmental factors at the start of retirement predict longitudinal changes in
physical activity and sedentary behaviors during the first years of retirement.
Second, moderating effects of gender and educational levels were examined.
METHODS: This longitudinal study was conducted in Flanders, Belgium. In total,
180 recently retired (>1 month, <2 years at baseline) adults completed a postal
questionnaire twice (in 2012-2013 and two years later in 2014-2015). The
validated questionnaire assessed socio-demographic information, physical
activity, sedentary behaviors, and psychological, social and physical
environmental characteristics. Multiple moderated hierarchic regression analyses
were conducted in SPSS 22.0. RESULTS: Higher perceived residential density (p <
0.001) and lower aesthetics (p = 0.08) predicted an increase in active
transportation (adjusted R2 = 0.18). Higher baseline self-efficacy was associated
with an increase in leisure-time physical activity (p = 0.001, adjusted R2 =
0.13). A more positive perception of old age (p = 0.04) and perceiving less
street connectivity (p = 0.001) were associated with an increase in screen time
(adjusted R2 = 0.06). Finally, higher baseline levels of modeling from friends (p
= 0.06) and lower perceived land use mix access (p = 0.09) predicted an increase
in car use (adjusted R2 = 0.06). A few moderating effects, mainly of educational
level, were found. DISCUSSION: Walkability characteristics (perceived residential
density) and self-efficacy at the start of retirement are the most important
predictors of longitudinal changes in active transportation and leisure-time
physical activity. Few moderating effects were found, so health interventions at
the start of retirement focusing on self-efficacy and specific walkability
characteristics could be effective to increase physical activity in recently
retired adults. No firm conclusions can be drawn on the importance of the
examined predictors to explain change in car use and screen time, possibly other
factors like the home environment, or automatic processes and habit strength are
more important to explain sedentary behaviors.
PMID- 28507819
TI - Radix Stellariae extract prevents high-fat-diet-induced obesity in C57BL/6 mice
by accelerating energy metabolism.
AB - Stellaria dichotoma L. is widely distributed in Ningxia and surrounding areas in
northwestern China. Its root, Radix Stellariae (RS), has been used in herbal
formulae for treating asthenic-fever, infection, malaria, dyspepsia in children
and several other symptoms. This study investigated whether the RS extract (RSE)
alleviates metabolic disorders. The results indicated that RSE significantly
inhibited body weight gain in high-fat (HF)-diet-fed C57BL/6 mice, reduced
fasting glucose levels, and improved insulin tolerance. Moreover, RSE increased
the body temperature of the mice and the expression of uncoupling proteins and
peroxisome proliferator-activated receptors in the white adipose tissue. Thus,
RSE alleviated metabolic disorders in HF-diet-fed C57BL/6 mice by potentially
activating UCP and PPAR signaling.
PMID- 28507818
TI - Screening of a natural compound library identifies emodin, a natural compound
from Rheum palmatum Linn that inhibits DPP4.
AB - Historically, Chinese herbal medicines have been widely used in the treatment of
hyperglycemia, but the mechanisms underlying their effectiveness remain largely
unknown. Here, we screened a compound library primarily comprised of natural
compounds extracted from herbs and marine organisms. The results showed that
emodin, a natural compound from Rheum palmatum Linn, inhibited DPP4 activity with
an in vitro IC50 of 5.76 uM without inhibiting either DPP8 or DPP9. A docking
model revealed that emodin binds to DPP4 protein through Glu205 and Glu206,
although with low affinity. Moreover, emodin treatment (3, 10 and 30 mg/kg, P.O.)
in mice decreased plasma DPP4 activity in a dose-dependent manner. Our study
suggests that emodin inhibits DPP4 activity and may represent a novel therapeutic
for the treatment of type 2 diabetes.
PMID- 28507821
TI - The density and biomass of mesozooplankton and ichthyoplankton in the Negro and
the Amazon Rivers during the rainy season: the ecological importance of the
confluence boundary.
AB - The boundary zone between two different hydrological regimes is often a
biologically enriched environment with distinct planktonic communities. In the
center of the Amazon River basin, muddy white water of the Amazon River meets
with black water of the Negro River, creating a conspicuous visible boundary
spanning over 10 km along the Amazon River. Here, we tested the hypothesis that
the confluence boundary between the white and black water rivers concentrates
prey and is used as a feeding habitat for consumers by investigating the density,
biomass and distribution of mesozooplankton and ichthyoplankton communities
across the two rivers during the rainy season. Our results show that mean
mesozooplankton density (2,730 inds. m-3) and biomass (4.8 mg m-3) were higher in
the black-water river compared to the white-water river (959 inds. m-3; 2.4 mg m
3); however an exceptionally high mesozooplankton density was not observed in the
confluence boundary. Nonetheless we found the highest density of ichthyoplankton
in the confluence boundary (9.7 inds. m-3), being up to 9-fold higher than in
adjacent rivers. The confluence between white and black waters is sandwiched by
both environments with low (white water) and high (black water) zooplankton
concentrations and by both environments with low (white water) and high (black
water) predation pressures for fish larvae, and may function as a boundary layer
that offers benefits of both high prey concentrations and low predation risk.
This forms a plausible explanation for the high density of ichthyoplankton in the
confluence zone of black and white water rivers.
PMID- 28507820
TI - Self-centeredness and selflessness: happiness correlates and mediating
psychological processes.
AB - The main objective of this research was to test central assumptions from the Self
centeredness/Selflessness Happiness Model. According to this model, while self
centered psychological functioning induces fluctuating happiness, authentic
durable happiness results from selflessness. Distinct mediating processes are
supposed to account for these relationships: afflictive affects (e.g., anger,
fear, jealousy, frustration) in the case of the former, and both emotional
stability and feelings of harmony in the case of the latter. We tested these
hypotheses in two studies based on heterogeneous samples of citizens (n = 547).
Factor analyses revealed that self-centeredness (assessed through egocentrism and
materialism) and selflessness (assessed through self-transcendence and
connectedness to other) were two distinct psychological constructs. Second, while
self-centeredness was positively and significantly related to fluctuating
happiness, selflessness was positively and significantly related to authentic
durable happiness. Finally, distinct psychological processes mediated these
relationships (study 2). On one hand, the relationship between self-centeredness
and fluctuating happiness was fully mediated by afflictive affects. On the other
hand, emotional stability and the feeling of being in harmony partially mediated
the relation between selflessness and authentic-durable happiness.
PMID- 28507822
TI - Estimating the effect of burrowing shrimp on deep-sea sediment community oxygen
consumption.
AB - Sediment community oxygen consumption (SCOC) is a proxy for organic matter
processing and thus provides a useful proxy of benthic ecosystem function. Oxygen
uptake in deep-sea sediments is mainly driven by bacteria, and the direct
contribution of benthic macro- and mega-infauna respiration is thought to be
relatively modest. However, the main contribution of infaunal organisms to
benthic respiration, particularly large burrowing organisms, is likely to be
indirect and mainly driven by processes such as feeding and bioturbation that
stimulate bacterial metabolism and promote the chemical oxidation of reduced
solutes. Here, we estimate the direct and indirect contributions of burrowing
shrimp (Eucalastacus cf. torbeni) to sediment community oxygen consumption based
on incubations of sediment cores from 490 m depth on the continental slope of New
Zealand. Results indicate that the presence of one shrimp in the sediment is
responsible for an oxygen uptake rate of about 40 umol d-1, only 1% of which is
estimated to be due to shrimp respiration. We estimate that the presence of ten
burrowing shrimp m-2 of seabed would lead to an oxygen uptake comparable to
current estimates of macro-infaunal community respiration on Chatham Rise based
on allometric equations, and would increase total sediment community oxygen
uptake by 14% compared to sediment without shrimp. Our findings suggest that
oxygen consumption mediated by burrowing shrimp may be substantial in continental
slope ecosystems.
PMID- 28507823
TI - Cells tile a flat plane by controlling geometries during morphogenesis of Pyropia
thalli.
AB - BACKGROUND: Pyropia haitanensis thalli, which are made of a single layer of
polygonal cells, are a perfect model for studying the morphogenesis of multi
celled organisms because their cell proliferation process is an excellent example
of the manner in which cells control their geometry to create a two-dimensional
plane. METHODS: Cellular geometries of thalli at different stages of growth
revealed by light microscope analysis. RESULTS: This study showed the cell
division transect the middle of the selected paired-sides to divide the cell into
two equal portions, thus resulting in cell sides >=4 and keeping the average
number of cell sides at approximately six even as the thallus continued to grow,
such that more than 90% of the cells in thalli longer than 0.08 cm had 5-7 sides.
However, cell division could not fully explain the distributions of intracellular
angles. Results showed that cell-division-associated fast reorientation of cell
sides and cell divisions together caused 60% of the inner angles of cells from
longer thalli to range from 100-140 degrees . These results indicate that cells
prefer to form regular polygons. CONCLUSIONS: This study suggests that
appropriate cell-packing geometries maintained by cell division and reorientation
of cell walls can keep the cells bordering each other closely, without gaps.
PMID- 28507824
TI - Non-Invasive Radiofrequency Field Treatment to Produce Hepatic Hyperthermia:
Efficacy and Safety in Swine.
AB - The Kanzius non-invasive radio-frequency hyperthermia system (KNiRFH) has been
investigated as a treatment option for hepatic hyperthermia cancer therapy. The
treatment involves exposing the patient to an external high-power RF (13.56 MHz)
electric field, whereby the propagating waves penetrate deep into the tumor
causing targeted heating based on differential tissue dielectric properties.
However, a comprehensive examination of the Kanzius system alongside any
associated toxicities and its ability to induce hepatic hyperthermia in larger
animal models, such as swine, are the subjects of the work herein. Ten Yucatan
female mini-swine were treated with the KNiRFH system. Two of the pigs were
treated a total of 17 times over a five-week period to evaluate short- and long
term KNiRFH-associated toxicities. The remaining eight pigs were subjected to
single exposure sessions to evaluate heating efficacy in liver tissue. Our goal
was to achieve a liver target temperature of 43 degrees C and to evaluate
toxicities and burns post-treatment. Potential toxicities were evaluated by
contrast-enhanced MRI of the upper abdomen and blood work, including complete
metabolic panel, complete blood count, and liver enzymes. The permittivities of
subcutaneous fat and liver were also measured, which were used to calculate
tissue specific absorption rates (SAR). Our results indicate negligible KNiRFH
associated toxicities; however, due to fat overheating, liver tissue temperature
did not exceed 38.5 degrees C. This experimental limitation was corroborated by
tissue permittivity and SAR calculations of subcutaneous fat and liver.
Significant steps must be taken to either reduce subcutaneous fat heating or
increase localized heating, potentially through the use of KNiRFH-active
nanomaterials, such as gold nanoparticles or single-walled carbon nanotubes,
which have previously shown promising results in murine cancer models.
PMID- 28507825
TI - Spatiotemporal Strategies for Joint Segmentation and Motion Tracking From Cardiac
Image Sequences.
AB - Although accurate and robust estimations of the deforming cardiac geometry and
kinematics from cine tomographic medical image sequences remain a technical
challenge, they have significant clinical value. Traditionally, boundary or
volumetric segmentation and motion estimation problems are considered as two
sequential steps, even though the order of these processes can be different. In
this paper, we present an integrated, spatiotemporal strategy for the
simultaneous joint recovery of these two ill-posed problems. We use a mesh-free
Galerkin formulation as the representation and computation platform, and adopt
iterative procedures to solve the governing equations. Specifically, for each
nodal point, the external driving forces are individually constructed through the
integration of data-driven edginess measures, prior spatial distributions of
myocardial tissues, temporal coherence of image-derived salient features,
imaging/image-derived Eulerian velocity information, and cyclic motion model of
myocardial behavior. The proposed strategy is accurate and very promising
application results are shown from synthetic data, magnetic resonance (MR) phase
contrast, tagging image sequences, and gradient echo cine MR image sequences.
PMID- 28507826
TI - Near-Infrared Imaging for Detecting Caries and Structural Deformities in Teeth.
AB - 2-D radiographs, while commonly used for evaluating sub-surface hard structures
of teeth, have low sensitivity for early caries lesions, particularly those on
tooth occlusal surfaces. Radiographs are also frequently refused by patients over
safety concerns. Translucency of teeth in the near-infrared (NIR) range offers a
non-ionizing and safe approach to detect dental caries. We report the
construction of an NIR (850 nm) LED imaging system, comprised of an NIR source
and an intraoral camera for rapid dental evaluations. The NIR system was used to
image teeth of ten consenting human subjects and successfully detected secondary,
amalgam-occluded and early caries lesions without supplementary image processing.
The camera-wand system was also capable of revealing demineralized areas, deep
and superficial cracks, and other clinical features of teeth usually visualized
by X-rays. The NIR system's clinical utility, simplistic design, low cost, and
user friendliness make it an effective dental caries screening technology in
conjunction or in place of radiographs.
PMID- 28507827
TI - Wearable Improved Vision System for Color Vision Deficiency Correction.
AB - Color vision deficiency (CVD) is an extremely frequent vision impairment that
compromises the ability to recognize colors. In order to improve color vision in
a subject with CVD, we designed and developed a wearable improved vision system
based on an augmented reality device. The system was validated in a clinical
pilot study on 24 subjects with CVD (18 males and 6 females, aged 37.4 +/- 14.2
years). The primary outcome was the improvement in the Ishihara Vision Test score
with the correction proposed by our system. The Ishihara test score significantly
improved ([Formula: see text]) from 5.8 +/- 3.0 without correction to 14.8 +/-
5.0 with correction. Almost all patients showed an improvement in color vision,
as shown by the increased test scores. Moreover, with our system, 12 subjects
(50%) passed the vision color test as normal vision subjects. The development and
preliminary validation of the proposed platform confirm that a wearable augmented
reality device could be an effective aid to improve color vision in subjects with
CVD.
PMID- 28507828
TI - Multiple Large Perineural (Tarlov) Cysts in the Sacrum of a Cadaver: A Case
Report and Review.
AB - Tarlov or perineural cysts are cerebrospinal fluid (CSF)-filled sacs found
between the perineurium and epineurium of the nerve roots. It is still unsure
whether the origin of these cysts is intradural or extradural. They can either be
asymptomatic or create a variety of negative impacts on comfort and quality of
life. In this case report, we describe the presentation of multiple Tarlov cysts
including one large cyst discovered during a routine cadaveric spinal dissection
and the relevant and related literature. To our knowledge, this is the only
cadaveric case report of Tarlov cysts and offers an interesting window into their
anatomy.
PMID- 28507829
TI - Bupropion-Induced Acute Dystonia with Dose Escalation and Use of Naranjo
Nomogram.
AB - Acute drug-induced dystonia is commonly associated with antipsychotic drugs,
antidepressants, antiemetics, and other medications. Bupropion (Wellbutrin and
Zyban) is one of the most frequently prescribed antidepressants in the United
States and Canada and smoking cessation aid. However, only few reported cases
have been published of acute dystonia including dystonia after discontinuation of
bupropion and even after a single dose of bupropion. Here, we report another case
concerning an acute dystonia resulting from bupropion after dose escalation. To
further assess this association, we used the Naranjo nomogram, which is a
questionnaire designed for determining the likelihood of whether an adverse drug
reaction is actually due to the drug rather than the result of other factors. Our
patient's total score was seven, suggesting that our patient had probable adverse
drug reaction. In summary, our case is that selected patients may experience dose
related acute dystonia as adverse reactions to bupropion sustained release (SR).
Since it is one of the most commonly prescribed antidepressants and smoking
cessation aids, clinicians should be aware of the potential dystonia associated
with bupropion.
PMID- 28507831
TI - Streptococcus Gordonii Empyema: A Case Report and Review of Empyema.
AB - Streptococcus gordonii (S. gordonii) is a pioneer oral bacteria that is
recognized as an agent of bacterial endocarditis. However, an extensive review of
the literature revealed no reported case of S. gordonii causing empyema. We
present a case of a 65-year-old male who presented with respiratory distress.
Physical examination revealed several dental caries with decreased breath sounds
in the bibasilar regions. A computed tomography (CT) scan of the chest and
abdomen demonstrated left-sided pleural effusion and a 4.3 cm x 2.8 cm splenic
abscess. He received intravenous (IV) antibiotics, and his blood cultures
remained negative. Drainage of the splenic abscess grew S. gordonii. A CT-guided
thoracentesis yielded 450 ml of exudative fluid. Pleural fluid cultures grew S.
gordonii. A CT scan of the head and neck ruled out an intra-oral abscess. He
received six weeks of IV penicillin with a follow-up CT scan showing resolution
of both the splenic abscess and the left parapneumonic effusion.
PMID- 28507830
TI - Dermatitis Due to Paederus Colombinus: Report of an Epidemic Outbreak of 68 Cases
in the Province of Darien, Panama.
AB - INTRODUCTION: Contact dermatitis due to Paederus is a particular form of accident
by animal contact. It is characterized by the sudden onset of erythematous and
vesicular lesions with burning sensation on exposed areas of the body. The aim of
this study was to describe the epidemiological and clinical findings of an
outbreak of Paederus dermatitis in Panama. METHODS: Clinical and epidemiological
findings of an outbreak of contact dermatitis caused by Paederus sp. in the
province of Darien in eastern Panama is reported. After reviewing the clinical
records, a clinical-epidemiological questionnaire was developed and used in 20
communities where reported cases were found. We captured and collected the
specimens for species characterization for three consecutive days using three
different methods of capture. RESULTS: During May-July, 2014, 68 cases of
Paederus irritant contact dermatitis occurred in 20 communities of the Darien.
Fifty-three percent were females. The age group of zero to five years had the
highest number of cases, 15 (22%). The most common clinical presentation was the
classical linear dermatitis (58%); 42% of the subjects had mirror image lesions,
multiple vesicular-pustular lesions, and crust lesions. Symptoms were most
commonly reported as a burning sensation (65%), followed by pruritus in 60%, pain
(25%), and fever (nine percent). A total of 81 specimens of Paederus were
collected, 68% in peridomiciliary areas. CONCLUSIONS: This Paederus sp.
dermatitis report represents one of the largest outbreak described in Latin
America and the diagnosis could be confused with others skin diseases like
pyodermitis or other contact dermatitis.
PMID- 28507832
TI - Disseminated Nocardia Farcinica Pneumonia with Left Adrenal Gland Abscess.
AB - Adrenal masses pose a diagnostic challenge. The differential diagnosis includes
functional adrenal tumors, incidentally found adrenal masses, metastases from an
unknown primary cancer, and abscesses. Infrequently, adrenal gland abscesses have
been reported in disseminated nocardiosis affecting immunocompetent and
immunocompromised patients. We report a case of disseminated Nocardia farcinica
pneumonia with an adrenal gland abscess in an immunocompetent patient with no
identified risk factors for nocardiosis.
PMID- 28507833
TI - Does Hemodynamic-Guided Heart Failure Management Reduce Hospitalization? A
Systematic Review.
AB - Heart failure (HF) is a pressing health concern as the expense of hospitalization
financially burdens the health care system. Hemodynamic monitoring has the
potential to detect increases in intracardiac filling pressures weeks before
clinical deterioration; hence, preliminary findings of volume overload with the
use of these devices may prevent the progression of disease and lead to a
reduction in HF-associated hospitalizations. We extensively searched PubMed, Ovid
SP, Embase, and Cochrane databases to identify all the possible studies that
assess the effect of hemodynamic monitoring on hospitalizations in HF patients.
The main outcomes considered were the rate of HF hospitalization, mortality,
quality of life, and improvement in New York Heart Association (NYHA) functional
class in the monitored group. Seven studies met all the eligibility criteria and
were incorporated in our systematic review. Out of the seven studies we reviewed,
three studies inserted the sensor in the pulmonary artery, three in the right
ventricle, and only one in the left atrium. On an average, the single study on
the left atrium showed the highest reduction (59.0%) in HF hospitalization
followed by the pulmonary artery (56.3%) and right ventricle (31.0%),
respectively. Our systematic review demonstrates that the use of hemodynamic
sensors in HF patients helps to reduce HF-related hospitalizations. Therefore, a
combination of outpatient monitoring via the use of hemodynamic sensors and fluid
management is needed to reduce HF hospitalizations and improve outcomes in HF
patients.
PMID- 28507834
TI - Clinical and Radiological Improvement Following Ozone Disc Nucleolysis: A Case
Report.
AB - The results of traditional open surgery for herniated intervertebral disc are
often limited by complications and failed back surgery syndrome (FBSS). Over the
past few decades, a considerable amount of research has been done in the field of
minimally invasive procedures as a treatment option for herniated intervertebral
disc disease. Ozone disc nucleolysis is one such procedure which has results
equal to or better than traditional surgery with virtually no complications. A 27
year-old post-partum female presented to the clinic with acute onset of severe
lower back pain radiating to the left lower limb for one month. The pain started
suddenly during labor and gradually increased over a period of few weeks post
partum. A magnetic resonance imaging (MRI) scan showed a large herniated disc
bulge at the L4-L5 level causing severe radiculopathy. There was no bladder or
bowel involvement. The patient was managed conservatively for three weeks.
However, she failed to show any signs of improvement. She opted to undergo ozone
disc nucleolysis under local anaesthesia. She showed significant improvement
immediately after the procedure and there was further improvement in symptoms
over a period of six weeks. Post-procedure follow-up at three months and six
months showed significant improvement on the visual analogue scale (VAS), which
was used to measure pain intensity and pain affect, along with the Oswestry
Disability Index (ODI), which was used to measure the degree of disability due to
the lower back pain. Her VAS score improved from nine to two at three months and
finally to one at six months, whereas the ODI score improved significantly from
46 to 10 at three months and eventually to four at six months. Ozone disc
nucleolysis is an efficacious, safe, durable, and cost-effective treatment option
for mild to moderate cases of herniated intervertebral disc which are resistant
to conservative management. However, randomized control trials are required to
build a long-term database regarding the efficacy and durability of ozone disc
nucleolysis as compared to other minimally invasive procedures and surgery. We
strongly believe that the availability of long-term data on ozone disc
nucleolysis would make it a more acceptable form of treatment for disc herniation
as compared to traditional surgery.
PMID- 28507835
TI - Endoscopic View of Gastroduodenal Artery Coils at the Base of Duodenal Ulcer in
Case of Recurrent Massive Upper Gastrointestinal Bleed.
AB - Helicobacter pylori (H. pylori) infection is one of the major causes of bleeding
peptic ulcer disease, which is associated with serious complications; therefore,
the eradication of H. pylori is essential to prevent these devastating
complications. Post-treatment follow-up is crucial to guarantee the eradication
of the organism and may be conducted via the urea breath test, the stool antigen
test, or a gastric biopsy. Acute massive upper gastrointestinal (UGI) bleeding is
one of the most common complications of peptic ulcer disease. Aggressive
treatment with early endoscopic hemostasis is essential for a favorable outcome.
Recurrent massive nonvariceal UGI bleeding remains a challenge. Optimal
management requires a multidisciplinary team of skilled endoscopists,
intensivists, experienced UGI surgeons, and interventional radiologists.
Endoscopy is the first-line treatment after hemodynamic stability is achieved.
The role of early elective surgery or angiographic embolization in selected high
risk patients to prevent re-bleeding remains controversial.
PMID- 28507836
TI - Microsurgical Removal of Microcatheter in the Middle Cerebral Artery During
Resection of an Arteriovenous Malformation Resection.
AB - Surgical resection is the current standard of therapy for the treatment of
arteriovenous malformation (AVM). Endovascular embolization is commonly used as
an adjunct prior to surgical resection because it is believed to reduce the risk
of intraoperative bleeding. Embolization has been associated with other
complications including visual deficits, vessel perforation, and catheter
adhesion. Catheter adhesion in which retained segments are contained within the
embolization cast are not necessarily cause for concern, but retention of larger
portions may confer an increased risk of thrombus formation. Such cases warrant
the removal of the retained segments or the patient may suffer serious
complications including death related to cerebrovascular events. In this case
report, we describe a unique case of catheter adhesion in which the extension of
the feeding catheter and the length of the introducer was left in its entirety
down to the entry portion at the level of the groin and later retrieved in its
entirety by craniotomy.
PMID- 28507837
TI - Non-Alcoholic Fatty Liver Disease Association with Cardiac Arrhythmias.
AB - Non-alcoholic fatty liver disease (NAFLD) has become a public health burden all
over the world. A significant percentage of the patients with NAFLD have a co
existing metabolic syndrome that is a risk factor for cardiovascular disease.
Clinical as well as epidemiological research shows that NAFLD is not simply
related to liver-related morbidity and mortality but is also associated with an
elevated risk of coronary heart disease (CHD), irregularities of cardiac function
as well as cardiac structure, valvular heart disease, and arrhythmias. Animal
studies suggest that NAFLD by itself exacerbates systemic/hepatic insulin
resistance, leads to atherogenic dyslipidemia and generates a number of pro
inflammatory, pro-coagulant and profibrogenic mediators which play an essential
role in the pathophysiology of cardiac abnormalities including arrhythmias.
Hence, it is suggested that the patients with NAFLD may derive benefit from
intensive monitoring and treatment methods to reduce the risk of CHD along with
other cardiac/arrhythmic complications. The intent of this clinical review is to
sum up the quickly increasing body of evidence that provides support for a robust
relationship between NAFLD and cardiac arrhythmias and to present the putative
biological mechanisms underlying this correlation.
PMID- 28507838
TI - Recurrent Stress Cardiomyopathy During COPD Exacerbation: Are Beta-adrenergic
Agonists Only to Blame?
AB - Takotsubo cardiomyopathy (TCM) is a variant of stress-induced cardiomyopathy,
characterized by transient left ventricular dysfunction that may be associated
with emotional or physical triggers. We present the case of a 51-year-old
Caucasian female with severe chronic obstructive pulmonary disease (COPD) who
presented with syncope and was found to have her second lifetime episode of
stress-induced cardiomyopathy. Eight months prior, she had been admitted with a
COPD exacerbation and was found to have left ventricular (LV) dysfunction with
ejection fraction (EF) of 22% attributed to TCM with subsequent normalization of
her left ventricular function. Recurrence of stress-induced cardiomyopathy
associated with COPD is a rare phenomenon and its presentation raises the
possibility of a common underlying mechanism.
PMID- 28507839
TI - Issues in Managing Hurthle Cell Carcinoma of Thyroid: A Case Report.
AB - A 61-year-old woman noticed a right neck lump in October 2001. Fine needle
aspiration showed follicular neoplasm, adenoma versus carcinoma. The ultrasound
scan showed a solid mass of maximum dimension of 3.7 cm. She had a right thyroid
lobectomy and isthmectomy in January 2002 (first surgery). The tissue specimen
showed a 4.5 cm Hurthle cell carcinoma (HCC) with vascular invasion. There were
no capsular invasion, extra-thyroidal extension, or margin involvement. A
completion left lobectomy (second surgery) was performed two weeks later.
Therefore the pathological stage is II (T3N0M0). She received adjuvant
radioactive iodine ablation for residual thyroid tissue. By 2003, she developed
local recurrence, which was resected (third surgery), followed by adjuvant
external beam radiotherapy. Unfortunately, she developed further recurrence in
the left main bronchus, as identified by Indium-111 Octreotide (Curium, Missouri,
USA) and positron emission tomography-computed tomography PET-CT imaging in 2006.
She underwent a left pneumonectomy (fourth surgery) in July 2006. In November
2007 she was found to have mediastinal recurrence which was treated with high
dose external beam radiotherapy. She initially responded but developed more local
recurrence and a lung metastasis by 2011. She was treated with brivanib with
ixabepilone, under a phase I clinical trial with mixed response. Her treatment
was discontinued secondary to toxicity and she succumbed to her disease in 2012.
This case report illustrates the natural history and clinical decision making for
patients diagnosed with HCC of the thyroid. Specifically, we highlight the
clinical issues surrounding the histopathological diagnosis, extent of surgical
resection, radioiodine diagnostic imaging/ablative treatment, as well as external
beam radiotherapy.
PMID- 28507840
TI - Cadaver-based Necrotizing Fasciitis Model for Medical Training.
AB - Necrotizing fasciitis is a devastating infectious disease process that is
characterized by extensive soft tissue necrosis along deep fascial planes,
systemic toxicity, and high mortality. Ultrasound imaging is a rapid and non
invasive tool that can be used to help make the diagnosis of necrotizing
fasciitis by identifying several distinctive sonographic findings. The purpose of
this study is to describe the construction of a realistic diagnostic training
model for necrotizing fasciitis using fresh frozen cadavers and common,
affordable materials. Presently, fresh non-embalmed cadavers have been used at
medical institutions for various educational sessions including cadaver-based
ultrasound training sessions. Details for the preparation and construction of a
necrotizing fasciitis cadaver model are presented here. This paper shows that the
images obtained from the cadaver model closely imitate the ultrasound appearance
of fluid and gas seen in actual clinical cases of necrotizing fasciitis.
Therefore, it can be concluded that this cadaver-based model produces high
quality sonographic images that simulate those found in true cases of necrotizing
fasciitis and is ideal for demonstrating the sonographic findings of necrotizing
fasciitis.
PMID- 28507841
TI - Skin Necrosis Caused by Simple Massage Equipment.
PMID- 28507842
TI - Pyoderma Gangrenosum after Deep Inferior Epigastric Perforator Breast
Reconstruction: Systematic Review and Case Report.
AB - BACKGROUND: Pyoderma gangrenosum (PG) is a rare skin disorder of the neutrophilic
dermatoses spectrum that can mimic wound infections in surgical patients. PG
after breast surgery has been reported but in limited amounts in autologous
breast reconstruction patients. We present the first case of PG after a delayed
bilateral deep inferior epigastric perforator flap breast reconstruction in the
setting of systemic disease along with a systematic review. METHODS: PubMed,
Ovid, and Web of Science were systematically searched to obtain cases of PG after
autologous breast reconstruction. Sixty articles were identified but only 16 were
relevant to this study. RESULTS: Systemic disease was present in 2 patients
(13%). Wound onset occurred typically 5 days after surgery. Fever and/or
leukocytosis was observed in 10 patients (63%). Wound cultures were positive in 2
patients (13%). Donor-site wounds were present in 9 patients (56%). Bilateral
breast wounds were present in 67% of bilateral cases. Debridement was performed
in 10 cases (63%). Skin graft or substitute was performed in 6 cases (38%).
Resection of autologous flap was performed in 3 cases (19%). All patients were
treated with systemic steroids (81%) and/or immunosuppressive medications (50%).
Complete wound healing occurred by 4 months on average. CONCLUSION: If early
ulcerative wounds develop at multiple sites after autologous breast
reconstruction with worsening after debridement and antibiotic therapy, then PG
should be considered. It is imperative that an early diagnosis and subsequent
treatment with steroids and/or immunosuppressive medications be initiated so
further surgical procedures, flap loss, and scarring can be minimized.
PMID- 28507843
TI - A New Local Flap Nipple Reconstruction Technique Using Dermal Bridge and
Preoperatively Designed Tattoo.
AB - BACKGROUND: Nipple-areolar reconstruction is the final step in breast
reconstruction. Reconstruction using local flaps and tattooing is useful in cases
of bilateral reconstruction, a small nipple-areolar complex (NAC) as the donor
site, and avoiding disturbance of the normal side and other body parts. However,
this method can cause projection loss and color fading of the nipple. Moreover,
the breast mound is reconstructed with an implant. METHODS: We performed nipple
areolar reconstruction of 90 nipples using clover-designed flaps oriented at 120
degrees and tattooing after breast silicone implantation in 64 women. The tattoo
was designed before flap operation and stained darker. Following donor site
closure, a dermal flap was made as a bridge for nipple support. The nipple space
was separated by the dermal flap from the breast mound and was filled with
subcutaneous tissue. The size of the reconstructed nipple projection was measured
postoperatively and 1 year later. The projection maintenance rate was calculated.
RESULTS: The heights of the nipple projection were 11.3 +/- 1.8 mm (95%
confidence interval [CI]: 10.9-11.7) just after the operation and 6.09 +/- 2.4 mm
(95% CI: 5.6-6.6) 1 year later. The actual range of nipple projection between
these 2 heights was 5.2 +/- 2.4 mm (95% CI: 4.7-5.7). The maintenance rate of the
reconstructed nipple projection after 12 months was 54.1 +/- 20.9 (95% CI: 49.7
58.5). The nipple color was maintained for over a year. CONCLUSIONS: Our nipple
areolar reconstruction technique could maintain the projection and color of the
reconstructed nipple for a long period. Good outcomes were obtained in this
implant-based breast reconstruction.
PMID- 28507845
TI - Surgical Factors Associated with Prolonged Hospitalization after Reconstruction
for Oncological Spine Surgery.
AB - BACKGROUND: Posterior trunk reconstruction is increasingly possible as a result
of advances in spinal instrumentation, reconstructive approaches, and
perioperative critical care. Extensive cases often require a muscle flap or
complex closure to obliterate dead space. Postsurgical wound complications and
subsequent reoperations can lead to neural injury, higher hospital costs, and
longer hospitalizations. We aim to identify risk factors that are associated with
increased length of stay (LOS) for patients receiving flaps to close a spinal
defect. METHODS: A single institution, retrospective cohort study was performed
on all patients from 2002 to 2014 who received a muscle flap to close a spine
defect. Medical and perioperative variables that were significantly associated
with LOS (P < 0.05) in univariate analysis were included in a stepwise regression
model. RESULTS: A total of 288 cases were identified. Presence of
instrumentation, preoperative chemotherapy, wound dehiscence, cerebrospinal fluid
leak, partial/total flap loss, and medical morbidity occurrence were all
independently associated with increased LOS in a combined multivariate model (P <
0.02 for each of the 6 variables). Importantly, Kaplan-Meier analysis
demonstrated that postoperative wound dehiscence increased LOS by 12 days.
CONCLUSIONS: Spinal tumor resections often create large cavitary defects that
necessitate the use of muscle flaps for closure. Patients who have received
adjuvant chemotherapy require instrumentation, or those who develop specific
wound-related or medical complications are at increased risk for prolonged
hospitalization after spinal reconstruction. Thus, implementing measures to
mitigate the occurrence of these adverse events will reduce costs and decrease
the length of hospitalization.
PMID- 28507844
TI - An Innovative Risk-Reducing Approach to Postmastectomy Radiation Delivery after
Autologous Breast Reconstruction.
AB - INTRODUCTION: Postmastectomy radiation therapy (PMRT) has known deleterious side
effects in immediate autologous breast reconstruction. However, plastic surgeons
are rarely involved in PMRT planning. Our institution has adopted a custom bolus
approach for all patients receiving PMRT. This offers uniform distribution of
standard radiation doses, thereby minimizing radiation-induced changes while
maintaining oncologic safety. We present our 8-year experience with the custom
bolus approach for PMRT delivery in immediate autologous breast reconstruction.
METHODS: All immediate autologous breast reconstruction patients requiring PMRT
after 2006 were treated with the custom bolus approach. Retrospective chart
review was performed to compare the postirradiation complications, reconstruction
outcomes, and oncologic outcomes of these patients with those of previous
patients at our institution who underwent standard bolus, and to historical
controls from peer-reviewed literature. RESULTS: Over the past 10 years, of the
29 patients who received PMRT, 10 were treated with custom bolus. Custom bolus
resulted in fewer radiation-induced skin changes and less skin tethering/fibrosis
than standard bolus (0% vs 10% and 20% vs 35%, respectively), and less volume
loss and contour deformities compared with historical controls (10% vs 22.8% and
10% vs 30.7%, respectively). CONCLUSIONS: Custom bolus PMRT minimizes radiation
delivery to the internal mammary vessels, anastomoses, and skin; uniformly doses
the surgical incision; and provides the necessary radiation dose to prevent
recurrence. Because custom bolus PMRT may reduce the deleterious effects of
radiation on reconstructive outcomes while maintaining safe oncologic results, we
encourage all plastic surgeons to collaborate with radiation oncologists to
consider this technique.
PMID- 28507846
TI - Contracted Nose Correction with Dermofat and Conchal Cartilage.
PMID- 28507847
TI - Plastic and Reconstructive Surgery in Global Health: Let's Reconstruct Global
Surgery.
AB - Since the inception of the Lancet Commission in 2013 and consequent
prioritization of Global Surgery at the World Health Assembly, international
surgical outreach efforts have increased and become more synergistic. Plastic
surgeons have been involved in international outreach for decades, and there is
now a demand to collaborate and address local need in an innovative way. The aim
of this article was to summarize new developments in plastic and reconstructive
surgery in global health, to unify our approach to international outreach.
Specifically, 5 topics are explored: current models in international outreach,
benefits and concerns, the value of research, the value of international surgical
outreach education, and the value of technology. A "Let's Reconstruct Global
Surgery" network has been formed using Facebook as a platform to unite plastic
and reconstructive surgeons worldwide who are interested in international
outreach. The article concludes with actionable recommendations from each topic.
PMID- 28507848
TI - The Marriage of Sartorius and Tensor Fasciae Latae in Treating Vascular
Prosthetic Graft Infections.
AB - BACKGROUND: Vascular prosthetic graft infection in the groin is associated with
high morbidity and mortality. This article presents a case series on the use of 2
flaps in the treatment of this condition. METHODS: Five patients, mean age 65
years (range, 49-74 years), with significant comorbidity were treated for an
exposed and infected vascular prosthetic graft in the groin with a combination of
sartorius muscle (SM) flap and tensor fascia lata (TFL) myocutaneous flap after
debridement and start of microbiologic culture-guided antibiotic treatment. The
SM flap was used to cover the exposed graft. To obtain stable wound coverage, the
SM and remaining groin defect were closed with a pedicle TFL flap. RESULTS: All
flaps survived, with only 1 TFL flap suffering a small tip necrosis. All patients
obtained stable wound coverage. Donor-site morbidity was minimal. During the
follow-up, mean 46 months (range, 15-79 months), 1 patient had a recurrence after
15 months due to a kink in the elongated prosthetic graft that protruded through
the skin alongside the SM and TFL flaps. CONCLUSIONS: The combination of SM and
TFL flaps could be a new treatment option for patients who have an exposed and
infected vascular prosthetic graft in the groin. This flap combination could also
be used as a prophylactic procedure for those patients with a high risk to
develop such a serious complication.
PMID- 28507849
TI - Difference in Success Treating Proximal Interphalangeal and Metacarpophalangeal
Joints with Collagenase: Results of 208 Treatments.
AB - BACKGROUND: Dupuytren disease (DD) is a fibroproliferative disorder of the palmar
fasciae causing extension deficit and impaired hand function. Treatment with
injection of collagenase clostridium histolyticum (CCH) is a nonsurgical
treatment method. The aim of this study was to evaluate the difference in
efficiency and recurrence at 12-month follow-up when treating metacarpophalangeal
(MP) and proximal interphalangeal (PIP) joints with CCH. None of the patients had
received previous treatments of their condition. METHODS: This study is a
prospective study of a consecutive series of patients with DD presenting with an
extension deficit greater than 20 degrees affecting the MP or PIP joint.
RESULTS: We found a mean reduction in extension deficit of 47 degrees (91%) for
MP joints and 47 degrees (76%) for PIP joints. Full correction (max 5 degrees
deficit) was achieved in 76% of MP and 28% of PIP joints. Skin rupture was seen
in 34% of treatments. The 1-year relapse rate was 15% for MP and 67% for PIP
joints. The reduction in quickDASH score was only statistically significant for
MP joints at 1 year. Eighty-one percent of all patients reported being satisfied
or very satisfied. No major adverse events were recorded. CONCLUSION: Excellent
results can be achieved in the treatment of MP-joint contractures, whereas the
success rate is significantly lower and recurrence rate is greater for PIP
joints.
PMID- 28507850
TI - Distally Based Sural Artery Peroneus Flap (DBSPF) for Foot and Ankle
Reconstruction.
AB - BACKGROUND: Reconstruction of soft-tissue defects in lower third of leg, ankle,
and foot has been a challenge and reconstructive surgeons have been trying to
innovate different flaps. To solve this issue, we propose a distally based sural
artery peroneus flap (DBSPF) in which we include superficial portion of the
peroneus brevis muscle and its blood supply with the peroneal artery distally.
The aim of this study was to evaluate the functional outcome and its usefulness
over conventional distal sural artery flap or other local options available.
METHODS: This is a case series of 20 patients that include a DBSPF that was done
for defects around ankle, distal leg, and foot caused by trauma or tumor ablation
within the period of June 2013 to March 2015 in Kasralainy Hospital, Cairo. All
cases were evaluated according to flap vascularity, distal reach of flap,
aesthetic outcome, and donor-site morbidity. RESULTS: All flaps survived. One
flap developed venous congestion that subsided spontaneously with limb elevation.
The flap dimension ranged from 42 cm to 442 cm2, and it reached the midfoot
easily. The pivot point was kept as low as 2-6 cm from lateral malleolus
according to location of perforators. The ankle stability was maintained, and the
desired aesthetic outcome was achieved. CONCLUSIONS: The DBSPF is an addition to
the armamentarium in plastic surgery for defects around ankle, distal leg, and
foot. It is an easy and swift procedure as compared with complex microsurgical
reconstruction.
PMID- 28507851
TI - Reconstruction after Excision of Hidradenitis Suppurativa: Are Skin Grafts Better
than Flaps?
PMID- 28507852
TI - Survival Differences in Women with and without Autologous Breast Reconstruction
after Mastectomy for Breast Cancer.
AB - BACKGROUND: Breast reconstruction (BR) is an option for women who are treated
with mastectomy; however, there has been concern regarding the oncologic safety
of BR. In this study, we evaluated recurrences and mortality in women treated
with mastectomy and compared outcomes in those treated with mastectomy alone to
those with mastectomy plus transverse rectus adbominis (TRAM) flap BR. METHODS:
The prospective cohort study included women treated with mastectomy at Women's
College Hospital from 1987 to 1997. Women with TRAM flap BR were matched to
controls based on age and year of diagnosis, stage, and nodal status. Patients
were followed from the date of diagnosis until death or date of last follow-up.
Hazard ratios were generated to compare cases and controls for outcome variables
using Cox's proportional hazards models. RESULTS: Of 443 women with invasive
breast cancer, 85 subjects had TRAM flap BR. Sixty-five of these women were
matched to 115 controls. The mean follow-up was 11.2 (0.4-26.3) years. There were
no significant differences between those with and without BR with weight, height,
or smoking status. Women with TRAM flap were less likely to experience a distant
recurrence compared to women without a TRAM flap (relative risk, 0.42; P =
0.0009) and were more likely to be alive (relative risk, 0.54; P = 0.03).
CONCLUSIONS: Women who elect for TRAM flap BR after an invasive breast cancer
diagnosis do have lower rates of recurrences and mortality than women treated
with mastectomy alone. This cannot be explained by differences in various
clinical or lifestyle factors.
PMID- 28507854
TI - A Novel Needle Structure that Can Avoid Intravascular Injection of Any Filler.
AB - With increasing use of dermal fillers, more and more adverse effects are
reported. The most devastating one is intravascular injection. We propose a novel
needle prototype that allows physicians to prevent intravascular injection.
PMID- 28507853
TI - Ulnar Head Reconstruction with Microvascular Second Metatarsal.
AB - BACKGROUND: The distal radioulnar joint along with the interosseous ligament of
the forearm and the proximal radioulnar joint, form a functionally integrated
system responsible for the pronation-supination of the hand. The distal ulna, the
so-called ulnar head, is an integral part of this system. Apart from its well
known role in forearm rotation, the ulnar head is essential in transverse load
transmission through the distal radioulnar joint upon resisted elbow flexion.
Autologous reconstruction of ulnar head would theoretically be beneficial with
respect to prostheses. METHODS: Three cases of ulnar head reconstruction with
microvascular second metatarsal are reported herein including trauma,
oncological, and congenital ethiologies. RESULTS: The clinical result was good
without complaints of instability. CONCLUSIONS: The cases included in this
series, although heterogeneous, indicate that this treatment may be feasible also
in postoncological resections and in congenital cases.
PMID- 28507855
TI - Composite Arteriovenous Radial Conduit Flap for Lower Limb Reconstruction.
AB - In complex lower limb trauma, the healthy recipient vessels can be far from the
defect to be reconstructed due to the usually high-energy injury sustained. The
use of vein grafts, either directly or in the form of arteriovenous loops, is the
usual solution in these cases. In the vein graft donor-depleted patient, other
options are required; the composite arteriovenous radial conduit flap may be a
useful resort in these situations.
PMID- 28507856
TI - Reverse Radial Forearm Flap.
AB - Supplemental Digital Content is available in the text.
PMID- 28507858
TI - Reconstructing Discontinuous Facial Defects with Simultaneous Ulnar Perforator
Free Flaps.
AB - Multiple, simultaneous skin cancers of the face are common. This is the first
description of reconstructing discontinuous facial defects (i.e., separate sites
of the face) with simultaneous ulnar perforator flaps. The distinct innovations
of this multiple flap design are the ability to restrict the harvest site to one
extremity, to obtain vein and arterial grafts from the same extremity, and to
create multiple flaps with minimal hirsutism and bulk. We present a case of a 57
year-old male with multiple basal cell carcinomas who underwent wide local
excisions of the right upper lip and cheek and of the left lower eyelid and
infraorbital cheek. Two left-sided ulnar perforator free flaps were used for
reconstruction with the outcome of normal oral competence and eyelid function.
When faced with discontinuous facial defects, reconstruction with simultaneous
ulnar perforator flaps is a useful option because of the advantages of matching
the thinness and pliability of the resected skin, reducing the number of harvest
sites and preventing the distortion and contraction that can be seen with local
advancement flaps or skin grafts.
PMID- 28507857
TI - Greater Omental Lymph Node Flap for Upper Limb Lymphedema with Lymph Nodes
depleted Patient.
AB - BACKGROUND: The greater omentum is supplied by the right, middle, and left
omental arteries, which arise from the right and left gastroepiploic arteries.
All or part of the greater omentum can be harvested based on this blood supply
for free tissue transfer. It has stimulated new interest in its use as the donor
site in the treatment of lymphedema. For patients who have failed other
management options or have limited peripheral lymph node donor sites, the greater
omental lymph node flap may offer the best chance for lymphedema treatment.
METHODS: We report a 59-year-old woman with a history of left breast cancer who
was treated with left modified radical mastectomy and axillary lymph node
dissection and developed left upper extremity Grade IV lymphedema. She received
vascularized groin lymph node transfer and lymphaticovenous anastomosis, but the
result was not satisfactory. She also had nasopharyngeal cancer that was treated
with radiotherapy to the head and neck, making use of the submental lymph nodes
flap impossible. Due to a lack of other options of lymph node donor sites, the
split greater omental lymph node flap (GOLF) was used. RESULTS: After surgery, it
showed an arm circumference reduction of 42.9% above the elbow and 36.4% below
the elbow at an 8-month follow-up. There was no intraabdominal complication.
CONCLUSIONS: The split GOLF has shown good results in a peripheral lymph node
depleted lymphedema patient. Using a laparoscopic technique for flap harvest has
less risk of donor site morbidity and hides scarring.
PMID- 28507859
TI - The Double Volar Flap Technique for Aesthetic Repair of Syndactyly and
Polysyndactyly of Toe without Skin Grafting.
AB - BACKGROUND: Aesthetic repair of syndactyly of the toes is desirable because
patients may have psychological concerns about its appearance. There are 2
important factors for the aesthetic repair of syndactyly of the toe. One is to
hide the operative scar from the visual site (dorsal site), whereas the other is
to create an interdigital space close to the normal anatomical skin
characteristics (2 general types of skin: glabrous and hairy). METHODS: In total,
12 patients (4 males and 8 females) with 15 syndactylous webs were operated on by
using the double volar flap technique. The following 3 local flaps were designed
with this technique: an M-shaped flap designed on the dorsal side of the
interdigital region (flap A) and double volar flaps (flaps B and C) designed on
the volar side of the interdigital region. Flap A was used for reconstruction of
the web slope, whereas flaps B and C were used for reconstruction of the proximal
sidewall of toes. RESULTS: The corrected toes showed a deep and natural
interdigital commissure with no exposure of skin grafts or conspicuous scars on
the dorsal visible side. The scars on the volar side were also inconspicuous.
CONCLUSIONS: The double volar flap method for repair of syndactyly and
polysyndactyly of the toes has the same advantages as those of the local flap
method, in addition to an optimum aesthetic result through matching with the
normal anatomical skin characteristic of the interdigital space and hiding of the
operative scar from the visual site.
PMID- 28507860
TI - Aging and Sexual Differences of the Human Skull.
AB - BACKGROUND: The aging process of the face comprises all layers: skin,
subcutaneous fat, muscles, and skeleton, and the signs of aging depend mainly on
which layer is mostly affected. OBJECTIVE: To evaluate the aging facial skeleton,
as well as establish the sexual differences, areas with a strong predisposition
to resorption, and aesthetic repercussion for better treatment approach. METHODS:
Skulls from the Forensic Anthropology Department of the Institute of Forensic
Medicine of Belo Horizonte, Brazil, were classified according to gender and age
group (i.e., <20 years, 20-50 years, >50 years). Structural changes were
classified according to gender and age group. RESULTS: Of the 241 skulls
included, 192 were male skulls and 49 female. Sexual dimorphism and age-related
peculiarities are described herein. CONCLUSIONS: The knowledge of the anatomy of
the aging face, taking into consideration all the layers (skin, fat pads,
muscles, and bones), as a whole, for the treatment of folds and shadows is vital
for a better and more natural final aesthetic outcome.
PMID- 28507861
TI - Absence of Ulnar Artery Inflow Detected by Allen's Test Prior to Radial Forearm
Free Flap.
AB - Radial forearm free flaps are commonly used for soft-tissue reconstruction after
resection of head and neck cancer. It is perfused by the radial artery, leaving
the ulnar artery for perfusion of the hand and digits. The absence of distal
ulnar artery and associated superficial palmar arch, however, has not been
reported in cadaveric dissection. We report a case of unilateral ulnar artery
flow absence, detected by Allen's test, during preoperative preparation for a
radial forearm free flap. Based on the simplicity, safety, and ease, we recommend
Allen's test to be performed preoperatively on every patient for whom such a flap
is a consideration.
PMID- 28507862
TI - Eyelid Reconstruction Using Oral Mucosa and Ear Cartilage Strips as Sandwich
Grafting.
AB - BACKGROUND: The eyelid structure can be divided into an inner layer and an outer
layer. Reconstruction of a full-thickness eyelid defect is accomplished by full
thickness composite tissue transfer or combined layered reconstruction. We
present a new technique for inner layer reconstruction using ear cartilage and
oral mucosa. METHODS: The oral mucosa graft is harvested from the inner side of
the lower lip to fit the defect size and shape. The ear cartilage graft is
harvested as a rectangular strip. The harvested mucosa is sutured to the defect
margin and the cartilage strip graft is interposed to the defect. Finally, the
outer layer of the defect is covered with skin flaps. Consequently, the ear
cartilage graft is sandwiched between the mucosa graft and the skin flap.
RESULTS: We used this technique for the reconstruction of 13 full-thickness
eyelid defects of various locations, sizes, and shapes. Ten cases involved the
lower eyelid, 2 cases involved the lower eyelid including the medial canthus, and
1 case involved the upper eyelid. The oral mucosa graft survived in all patients.
The reconstructions were successful and there were no postoperative reports of
conjunctival or corneal irritation. CONCLUSIONS: The present technique using a
combination of an ear cartilage strip graft and oral mucosa graft is an easy and
versatile technique for reconstruction of inner layer eyelid defects. We believe
that the beneficial effects of tears, which are richly oxygenated, improved
survival of the grafted mucosa.
PMID- 28507864
TI - Technical Tip: Mark Scarpa's Fascia to Facilitate Proper Abdominal Closure During
Autologous Breast Reconstruction.
PMID- 28507863
TI - Amnion Membrane in Diabetic Foot Wounds: A Meta-analysis.
AB - BACKGROUND: Amniotic membrane is tissue obtained from human placenta rich in
cytokines, growth factors, and stem cells that possess the ability to inhibit
infection, improve healing, and stimulate regeneration. METHODS: A meta-analysis
was performed examining randomized controlled trials comparing amniotic tissue
products with standard of care in nonhealing diabetic foot ulcers including
PubMed, Cochrane Central Register of Controlled Trials, and the Cochrane Database
of Systematic Reviews. RESULTS: A search of 3 databases identified 596
potentially relevant articles. Application of selection criteria led to the
selection of 5 randomized controlled trials. The 5 selected randomized controlled
trials represented a total of 311 patients. The pooled relative risk of healing
with amniotic products compared with control was 2.7496 (2.05725-3.66524, P <
0.001). CONCLUSIONS: The current meta-analysis indicates that the treatment of
diabetic foot ulcers with amniotic membrane improves healing rates in diabetic
foot ulcers. Further studies are needed to determine whether these products also
decrease the incidence of subsequent complications, such as amputation or death,
in diabetic patients.
PMID- 28507865
TI - Reconstitution of Human Keloids in Mouse Skin.
AB - BACKGROUND: Keloids are a dermal fibroproliferative scar of unknown etiology.
There is no good animal model for the study of keloids, which hinders the
development and assessment of treatments for keloids. METHODS: Human
keratinocytes and dermal fibroblasts were isolated from 3 human skin tissues:
normal skin, white scars, and keloids. A mixed-cell slurry containing
keratinocytes and dermal fibroblasts was poured into a double chamber implanted
on the back of NOD/Shi-scid/IL-2Rgammanull mice. After 12 weeks, the recipient
mice had developed reconstituted human skin tissues on their backs. These were
harvested for histological studies. RESULTS: Macroscopically, the reconstituted
skins derived from both normal skin and white scars were similar to normal skin
and white scars in humans, respectively. Keloid-derived reconstituted skins
exhibited keloid-like hypertrophic nodules. Histological findings and
immunohistochemical staining confirmed that the reconstituted skin tissues were
of human origin and the keloid-derived reconstituted skin had the typical
features of human keloids such as a hypertrophic dermal nodule, collagen type
composition, orientation of collagen fibers, and versican expression. CONCLUSION:
The mouse model with humanized keloid tissue presented here should be a useful
tool for future keloid research.
PMID- 28507867
TI - Low-grade Cribriform Cystadenocarcinoma: A Review of the Literature and Case
Report.
AB - Low-grade cribriform cystadenocarcinoma (LGCCC) is a rare tumor of the salivary
gland that most often arises from the parotid gland. A 51-year-old man developed
a small mass on the right parotid gland 5 years ago. A preoperative magnetic
resonance image showed abnormal intensity, an atypical characteristic for such a
tumor; therefore, the diagnosis was difficult. Thus, a superficial parotidectomy
was performed as a total excisional biopsy to remove the tumor. Histopathological
analyses revealed that the tumor was composed of a single cyst comprising cells
containing mucosal fluid, with proliferation of large cells. Also, proliferation
of the tumor epithelium showed a papillary cribriform pattern of proliferation
with a partial ring form, and the tissue inside the tumor was replaced by a
hematoma. Mild cellular atypia was observed. Immunostaining for S-100 was
positive, and the Ki-67 ratio was <5%. These histopathological findings led to a
diagnosis of LGCCC of the parotid gland. At 54 months after surgery, the patient
has had no recurrence or facial palsy. LGCCC is a rare neoplasm of the salivary
gland and is listed in the current World Health Organization classification
(2005) as a variant of cystadenocarcinoma. This case suggests that a thorough
preoperative examination can lead to better diagnosis of rare tumors, including
LGCCC. Thus, if a plastic surgeon is to correctly diagnose and treat parotid
grand tumors, including LGCCC, then a detailed preoperative examination,
including imaging, a disease course review, a physical examination, and
differential diagnosis, should be considered carefully.
PMID- 28507868
TI - Chronological Order of Lipofilling during Implant Exchange.
PMID- 28507866
TI - Establishing Content Validity of the CLEFT-Q: A New Patient-reported Outcome
Instrument for Cleft Lip/Palate.
AB - BACKGROUND: The CLEFT-Q is a new patient-reported outcome instrument designed to
measure outcomes that matter to patients. The aim of this qualitative study was
to establish content validity of the CLEFT-Q in patients who differ by age and
culture. METHODS: Patients aged between 6 and 29 years were recruited from
plastic surgery clinics in Canada, India, Ireland, the Philippines, the
Netherlands and the United States. Healthcare providers and other experts
participated in a focus group or provided individual feedback. Input was sought
on all aspects of the CLEFT-Q (item wording, instructions, and response options),
and to identify missing content. Patient interviews and expert feedback took
place between September 2013 and September 2014. RESULTS: Sixty-nine patients and
44 experts participated. The first draft of the CLEFT-Q consisted of 163 items
measuring 12 constructs. The first round of feedback identified 92 items that
required revision. In total, 3 rounds of interviews, and the involvement of an
artist to create pictures for 17 items, were needed to establish content
validity. At the conclusion of cognitive interviews, the CLEFT-Q consisted of 13
scales (total 171 items) that measure appearance, health-related quality of life,
and facial function. The mean Flesch-Kincaid readability statistic for items was
1.4 (0 to 5.2). CONCLUSION: Cognitive interviews and expert review allowed us to
identify items that required re-wording, re-conceptualizing, or to be removed, as
well as any missing items. This process was useful for refining the CLEFT-Q
scales for further testing.
PMID- 28507869
TI - Superficial Circumflex Iliac Artery Perforator Flap for Dorsalis Pedis
Reconstruction.
AB - Reconstruction of dorsalis pedis with soft tissue is challenging because it needs
to preserve thin structure to ensure that the patient will be able to wear shoes.
Here, we report the use of a thin superficial circumflex iliac artery perforator
(SCIP) flap in dorsalis pedis reconstruction. A 67-year-old man presented with a
third-degree burn, which exposed his extensor tendons. A thin SCIP flap from the
left inguinal region measuring 15 * 4 cm was transferred to the dorsalis pedis
region. Postoperatively, no major cosmetic or functional problems were observed.
Because the invasiveness of the donor site is nearly same between SCIP flap and
skin graft from inguinal region, SCIP flap is better solution in point of
textural qualities for dorsalis pedis reconstruction.
PMID- 28507870
TI - Intraoperative Change in Defect Size during Maxillary Reconstruction Using
Surgical Guides Created by CAD/CAM.
AB - Surgical osteotomy guides created by computer-aided design/computer-aided
manufacturing (CAD/CAM) have been developed and are now widely used in
maxillofacial reconstruction. However, there are no standard procedures for
dealing with an intraoperative change in defect size. We report on a case in
which we used our CAD/CAM guides to deal with an intraoperative change in defect
size in a maxillary reconstruction. We planned the maxillary reconstruction using
a free fibula flap because of left maxillary sinus cancer in a 73-year-old man.
In Japan, we cannot use commercially supplied CAD/CAM guides because these have
not been approved by the government. We created novel CAD/CAM guides by using
free software and a low-cost 3D printer. We performed model surgery to check the
accuracy of the design and to prebend the titanium plates before the operation.
The actual defect in the maxilla was found to be smaller than that used in
preoperative planning. It was therefore necessary to rearrange the fibular
segments and to rebend the plates. Comparison between the preoperative and
postoperative 3D images showed that the deviation was 2-4 mm. In case that the
CAD/CAM guides become inapplicable because of an intraoperative change in defect
size, rearranging both the ends of set-up fibular segments and rebending the
plates in situ allows us to deal with the situation. However, because extra time
is needed to rearrange and rebend, the total operation and flap ischemic times
are not shortened.
PMID- 28507871
TI - Mammary Malignant Ulcer after Radiotherapy: Unpleasant Surprise.
AB - We present a case of a woman, 79 years old, followed by Psychiatry for depressive
episodes after breast cancer removal. She was operated on for ductal breast
carcinoma in 1983. Afterward she was submitted to adjuvant radiotherapy. She came
to our attention for a chronic skin ulcer that developed into the radio-treated
area about 4 years ago. We performed a skin biopsy and programed adipose tissue
grafts to promote wound healing. The result of the biopsy was unexpected: dermal
localization of not differentiated breast carcinoma. She is currently under
systemic chemotherapy treatment. The key message is to always perform a skin
biopsy of a chronic skin ulcer developed after breast cancer removal before
planning surgical reconstruction.
PMID- 28507872
TI - Multiple-level Replantation in Elderly Patients: Risk Versus Benefit.
AB - Multiple-level amputations of the upper extremity represent a surgical challenge
generally only attempted in young patients. This case demonstrates a successful
replantation in an elderly woman. The postoperative course was complicated by
disseminated intravascular coagulopathy most likely due to inadequate
resuscitation. Hand trauma is often underestimated in its general severity. Upper
extremity amputations need to be handled similar to polytraumatized patients.
PMID- 28507873
TI - Inferior Limb Salvage by Combined Free-tissue Transfer and the Crane Principle
Revisited.
AB - Aggressive treatment of ischemia of the lower extremities has decreased the
number of amputations in both diabetic and nondiabetic patients; combined
vascular reconstruction and microvascular free-flap transfer has been used to
improve distal perfusion and cover large tissue defects caused by the critical
limb ischemia during the past 30 years. We present our experience with a 71-year
old diabetic patient who underwent revascularization with a vascular bypass and a
simultaneous microvascular flap reconstruction for limb salvage after domestic
trauma. An extension of the "crane" principle was used to solve bypass exposure
due to wound late complication. After 1-year follow-up, the patient was able to
walk without pain. Combining 3 well-established methods of arterial
revascularization and free-flap transfer and the old "crane principle," we
achieved limb salvage, offering an alternative to below-knee amputation.
PMID- 28507874
TI - A 10-year Follow-up of a Free Vascularized Fibula Flap Clavicle Reconstruction in
an Adult.
AB - The free vascularized fibula flap has been widely used for clavicle
reconstruction. Limited evidence exists for the long-term outcome of clavicle
reconstruction using the free vascularized fibula flap in adults. We report the
functional and aesthetic outcome in a 52-year old man a decade after clavicle
reconstruction using a free vascularized fibula flap in combination with a
modified Richardson Hook Plate. At the 10-year follow-up, panoramic shoulder X
ray showed the modified Richardson Hook Plate had remained firmly in place with
the fibula and the hook positioned beneath the acromion. Functionally, the
patient presented with a constant shoulder score of 77, with a pain-free
symmetrical full range of motion. In conclusion, reconstruction of lateral
clavicle defect using free vascularized fibula flap in conjunction with modified
Richardson Hook plate may provide patients with excellent long-term functional
and aesthetic outcomes.
PMID- 28507875
TI - Digital Joint Reconstruction with Osteotendinous Joint Allograft: Experimental
Study in Rats.
AB - BACKGROUND: Fresh or frozen nonvascularized osteotendinous joint allografts
(OTJA) have not been used previously, clinically or experimentally, for
metacarpophalangeal joint reconstruction. Therefore, we evaluated the viability
of OTJA for metatarsophalangeal joint (MTJ) reconstruction in rats. METHODS: In
the experimental group of 12 Lewis rats, we reconstructed the MTJ of the third
digit of the hindlimb with a fresh, nonvascularized OTJA obtained from the same
digit from 12 donor rats. In the control group of 6 Lewis rats, an autologous
composite osteotendinous graft of the MTJ of the same digit was obtained and
repositioned in situ as an auto-transplant. Weight, pain, edema, dehiscence, and
wound infection were evaluated every 24 hours for 30 days postoperatively. At the
end of 30 days, we evaluated digit position, flexion and extension, passive
mobility, radiological bone healing, and histological grades of rejection.
RESULTS: We found no statistically different changes in weight, edema, pain,
digit position, or radiological bone healing in either group. No wound dehiscence
or infection was seen in any of the rats. Ten degrees of flexion and extension
mobility were lost in the control group; the experimental group lost up to 30
degrees (P = 0.009). Histologically, 9 of the experimental group rats (9/12, 75%)
showed rejection reactions compared with none of the controls (0%) (P = 0.009).
CONCLUSIONS: Fresh nonvascularized OTJA caused an immune reaction without
exposure of the graft, but with bone resorption. However, the rats maintained
digital form and alignment with decreased passive flexion and extension of 10-30
degrees.
PMID- 28507877
TI - Erratum: Efficacy of Autologous Platelet-rich Plasma Glue in Weight Loss Sequelae
Surgery and Breast Reduction: A Prospective Study: Erratum.
AB - [This corrects the article DOI: 10.1097/GOX.0000000000000823.].
PMID- 28507876
TI - Prediction of Skin Necrosis after Mastectomy for Breast Cancer Using Indocyanine
Green Angiography Imaging.
AB - BACKGROUND: In immediate tissue expander reconstruction following total
mastectomy for breast cancer, indocyanine green angiography (ICGA)-guided skin
trimming is useful for the prevention of complications. However, instances of
unclear ICGA contrast can occur with this method, which are difficult to judge as
to whether preventive trimming is warranted. To further improve the mastectomy
flap necrosis rate, more accurate objective parameters are necessary. METHODS:
The degree of clinical improvement was compared between 81 patients trimmed
according to the surgeon's judgment (non-ICGA group) and 100 patients with ICGA
guided trimming (ICGA group). We then retrospectively measured 3 parameters
[relative perfusion (RP); time (T) to reach RPmax; and slope (S = RP/T)
reflecting the rate of increase to RPmax] by using region of interest analysis
software and examined their relationships with skin necrosis. RESULTS: The rate
of grade III necrosis (reaching the subcutaneous fat layer) was significantly
lower in the ICGA group (4.8%) than in the non-ICGA group (17.8%; P < 0.05). The
specificity of RP for the diagnosis of skin necrosis was high (98.5%; cutoff
value, 34). However, the sensitivities of slope parameters were higher than RP.
CONCLUSIONS: ICGA-guided trimming decreased the rate of deep skin necrosis
requiring additional surgical treatment. Region of interest analysis indicated
that a relatively low percentage luminescence (RP < 34) was indicative of the
need for skin trimming, combined with a slow increase in the perfusion of the
mastectomy skin flaps.
PMID- 28507878
TI - Medical Journals and Social Media: More Alike Than Wanted?
PMID- 28507879
TI - Traumatic Cervical Unilateral and Bilateral Facet Dislocations Treated With
Anterior Cervical Discectomy and Fusion Has a Low Failure Rate.
AB - STUDY DESIGN: Retrospective radiographic and chart review. OBJECTIVE: To define
the rate and associated risk factors of treatment failure of anterior cervical
fusion for treatment of cervical facet dislocations. METHODS: Between 2004 and
2014, a retrospective review at a single level 1 trauma center identified 38
patients with unilateral or bilateral dislocated facet(s) treated with anterior
cervical discectomy and fusion (ACDF). Two patients were eliminated due to less
than 30-day follow-up. Demographic data, initial neurological exams, surgical
data, radiographic findings, and follow-up records were reviewed. RESULTS: Of the
36 patients with facet dislocations treated with ACDF using a fixed locking
plate, 16 were unilateral and 20 were bilateral. The mean age was 35 years (range
13-58). Mean follow-up was 323 days (range 30-1998). There were 3 treatment
failures (8%). Three of 7 (43%) endplate fractures failed (P < .01), and 1/28
(4%) facet fractures failed (P = .13). The mean time to failure was 4 weeks (1-7
weeks). One treatment failure had a facet fracture, and all 3 failures had an
associated endplate fracture. CONCLUSION: Treatment failure occurred in 3 out of
36 (8%) patients with facet fracture dislocations treated with anterior cervical
discectomy, fusion, and plating. Rates of failure are lower than has been
previously reported. Endplate fractures of the inferior level in jumped facets
appears to be a major risk factor of biomechanical failure. However, a facet
fracture may not be a risk factor for failure. In the absence of an endplate
fracture, ACDF is a reasonable treatment option in patients with single-level
cervical facet dislocation.
PMID- 28507880
TI - Risk and Cost of Reoperation After Single-Level Posterior Cervical Foraminotomy:
A Large Database Study.
AB - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To examine the risk of
undergoing another cervical spine surgery after single-level posterior cervical
foraminotomy (PCF) and analyze the costs of such reoperations. METHODS: Using the
PearlDiver database, we created database algorithms to identify cohorts of
patients who underwent single-level PCF and also had various reoperations of
interest, within 1, 2, and 4 years of follow-up. We also identified the per
patient average charge (PPAC) for each reoperation cohort. RESULTS: In the
Medicare cohort, the incidence of any reoperation was 8.3%, 9.8%, and 10.5%
within 1, 2, and 4 years of follow-up, respectively. The PPAC was $8520 for the
initial PCF procedure. When a second cervical surgery was performed, the PPAC was
$70 349 for anterior fusion, $15 760 for posterior decompression alone, and $77
976 for posterior decompression and fusion. In the UnitedHealth cohort, the
incidence of any reoperation was 13.6%, 16.7%, and 17.0% within 1, 2, and 4 years
of follow-up, respectively. CONCLUSIONS: The overall incidence of another
cervical spine operation was slightly higher in the Medicare population to that
in previous literature, but much higher in the UnitedHealth population. The most
common reoperation after PCF varied between the Medicare and UnitedHealth
datasets, and costs varied widely based on the procedure performed. This study
provides pertinent information that surgeons can use to discuss the risk of
reoperation with their patients.
PMID- 28507881
TI - Development and Validation of the iDI: A Short Self-Rating Disability Instrument
for Low Back Pain Disorders.
AB - STUDY DESIGN: Cross-sectional and longitudinal validation study. OBJECTIVE:
Development and validation of a short, reliable, and valid questionnaire for the
assessment of low back pain-related disability. METHODS: The iDI was created in a
stepwise procedure: (1) its development was based on the literature and
theoretical consideration; (2) outcome data were collected and evaluated in a
pilot study; (3) final validations were performed based on an international
multicenter spine surgery outcome study including 514 patients; (4) the iDI was
programmed for a tablet computer (iPad) and tested for its clinical
practicability. RESULTS: The final version of the iDI comprises of 8 simple
questions related to different aspects of disability with a 5-point Likert-type
answer scale. The iDI compared very well to the Oswestry Disability Index in
terms of reliability and validity. The iDI was demonstrated to be suitable for
data assessment on a tablet computer (iPad). CONCLUSIONS: The iDI is a short,
valid, and practicable tool that facilitates routine quality assessment in terms
of low back pain-related disability.
PMID- 28507882
TI - Aquaporin-1 Expression in Herniated Human Lumbar Intervertebral Discs.
AB - STUDY DESIGN: Case series. OBJECTIVE: Intervertebral disc (IVD) degeneration is
the cause of spondylosis. The pathogenesis is poorly understood, but disc
dehydration often plays a role. In this study, we aim to identify and quantify
aquaporin-1 (AQP1) in ex vivo human degenerated IVDs obtained intraoperatively
and to investigate the relationship between AQP1 levels and magnetic resonance
imaging (MRI) T2 intensity of the disc. METHODS: Ex vivo samples of nucleus
pulposus (NP) tissue from lumbar IVDs were obtained from 18 consecutive patients
who underwent surgery for disc herniation at L4/5 and L5/S1 level.
Immunohistochemistry was performed to determine the presence of AQP1 expression,
and this was quantified by Western blot analysis. AQP1 expression was compared to
preoperative IVD signal intensity on T2-weighted MRI. RESULTS: NP tissue was
obtained from 18 patients (9 for L4/5 level and 9 for L5/S1 level). AQP1
expression was detected in all samples by Western blot and immunohistochemistry.
AQP1 expression had a linear correlation with the preoperative IVD signal
intensity on T2-weighted MRI at L4/5 level (R2 = 0.90) and at L5/S1 level (R2 =
0.92). AQP1 expression was 52.2 +/- 59.0 at L5/S1 level and 15.9 +/- 20.6 at L4/5
(P = .10). CONCLUSIONS: Our results show that AQP1 can be detected in IVD
obtained from live human subjects. Increased AQP1 expression is associated with
greater disc hydration as measured by signal intensity on T2-weighted MRI. AQP1
may have a role in the dehydration associated with disc degeneration.
PMID- 28507884
TI - A Retrospective Analysis of Complications Associated With Bone Morphogenetic
Protein 2 in Anterior Lumbar Interbody Fusion.
AB - STUDY DESIGN: Retrospective review. OBJECTIVE: The aim of our study was to
quantify the frequency of complications associated with recombinant human bone
morphogenetic protein 2 (rhBMP-2) use in anterior lumbar interbody fusion (ALIF).
METHODS: The orthopedic subset of the Medicare database (PearlDiver) was queried
for this retrospective cohort study using International Statistical
Classification of Diseases 9 (ICD-9) and Current Procedure Terminology (CPT)
codes for ALIF procedures with and without rhBMP-2 between 2005 and 2010.
Frequencies of complications and reoperations were then identified within 1 year
from the index procedure. Complications included reoperations, pulmonary embolus,
deep vein thrombosis, myocardial infarction, nerve-related complications,
incision and drainage procedures, wound, sepsis, pneumonia, urinary tract
infections, respiratory, heterotopic ossification, retrograde ejaculation,
radiculopathy, and other medical complications. Odds ratios (ORs) and 95%
confidence intervals (CIs) were used to assess the statistical significance.
RESULTS: We identified a total of 41 865 patients who had an ALIF procedure. A
total of 14 384 patients received rhBMP-2 while 27 481 did not. Overall, 6016
(41.8%) complications within 1 year from surgery were noted within the group who
received rhBMP-2 and 12 950 (47.1%) complications within 1 year from surgery were
recorded in those who did not receive rhBMP-2 (OR = 0.81, CI = 0.77-0.84).
Overall, exposure to rhBMP-2 was associated with significantly decreased odds of
complications with exception to reoperation rates (0.9% rhBMP-2 vs 1.0% no rhBMP
2; OR = 0.88, CI = 0.71-1.09) and radiculopathy (4.4% rhBMP-2 vs 4.3% no rhBMP-2;
OR = 1.02, CI = 0.93-1.13). CONCLUSIONS: The use of rhBMP-2 in patients
undergoing ALIF procedure was associated with a significantly decreased rate of
complications. Further studies are needed to elucidate a true incidence of
complication.
PMID- 28507883
TI - Risk Factors for Medical and Surgical Complications Following Single-Level ALIF.
AB - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The objective of the study
was to determine rates of medical and surgical postoperative complications
following anterior lumbar interbody fusion (ALIF) along with their associated
predictors. METHODS: Using the American College of Surgeons National Surgical
Quality Improvement database, patients who underwent single-level ALIF surgery
from 2006 to 2013 were identified. The 30-day rate of postoperative medical and
surgical complications along with associated risk factors were evaluated by
multivariable logistic regression. RESULTS: In total, 1474 patients were included
in the analysis. The overall rate of complications was 14.5%. The medical
complication rate was 12.7%, while the surgical complication rate was 2.8%.
Predictors of surgical complications were diabetes (odds ratio [OR] = 2.79, 95%
CI = 1.20-6.01, P = .009), corticosteroid dependence (OR = 4.94, 95% CI = 1.73
14.08, P = .003), and preoperative transfusion of >4 units (OR = 7.12, 95% CI =
1.43-35.37, P = .016). Predictors of medical complications were longer operative
times (OR = 4.25, 95% CI = 2.90-6.24, P < .001), preoperative anemia (OR = 2.29,
95% CI = 1.50-3.50, P < .001), >10% weight loss prior to surgery (OR = 6.79, 95%
CI = 1.01-45.93, P = .049), and more severe American Society of Anesthesiologists
classification (OR = 2.18, 95% CI = 1.54-3.11, P < .001). CONCLUSIONS: The
present study determines postoperative medical and surgical complications among
patients undergoing ALIF. The risk factors elucidated in this study indicate that
clinical practices to curtail complications should be targeted toward patients
with preoperative anemia, weight loss, corticosteroid dependence, and toward
those at risk for perioperative transfusions.
PMID- 28507885
TI - Effect of Cervical Sagittal Balance on Laminoplasty in Patients With Cervical
Myelopathy.
AB - STUDY DESIGN: Retrospective clinical study. OBJECTIVE: We evaluated the
relationship between cervical sagittal alignment parameters and clinical status
in patients with cervical myelopathy and analyzed the effect of cervical sagittal
balance on cervical laminoplasty. METHODS: Patients with cervical myelopathy (n =
110) who underwent laminoplasty were included in this study. The relationship
between cervical sagittal alignment parameters and clinical status was evaluated.
The changes in radiographic cervical sagittal parameters and clinical status 2
years after surgery were compared between patients with preoperative C2-7 SVA
>=35 mm (group A) and those with preoperative C2-7 SVA <35 mm (group B). RESULTS:
Preoperatively, C2-7 SVA had no correlation with defined health-related quality
of life evaluation scores. At 2-year follow-up, the improvement in SF-36 physical
component summary was significantly lower in group A than in group B. The
postoperative change of C2-7 SVA did not significantly differ in 2 groups.
Patients in group A maintained cervical regional balance after laminoplasty but
experienced extensive postoperative neck pain. CONCLUSIONS: Our patients with a
C2-7 SVA of >=35 mm maintained cervical regional balance after laminoplasty and
their improvement in myelopathy was equivalent to that in patients with a C2-7
SVA of <35 mm. However, the patents with a C2-7 SVA of >=35 mm experienced severe
postoperative neck pain. C2-7 SVA is a parameter worth considering because it can
lead to poor QOL and axial neck pain after laminoplasty.
PMID- 28507886
TI - Racial Disparities in Elderly Patients Receiving Lumbar Spinal Stenosis Surgery.
AB - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To evaluate for racial
disparities in elderly patients having undergone lumbar spinal stenosis surgery.
METHODS: The US Medicare Provider Analysis and Review database (records from 2005
to 2011) was used to identify patients over the age of 65 years, diagnosed with
lumbar spinal stenosis, and having undergone lumbar laminectomy or fusion
surgery. Blacks were compared to Whites in both unmatched and propensity score
matched populations. The data was analyzed with univariate (chi2 and Wilcoxon
rank sum tests for unmatched comparison, and McNemar exact and signed rank sum
tests for matched comparison) and multivariate models. RESULTS: Query of the data
resulted in a study sample of 12 807 patients; 514 (4.0%) were identified as
Black and 12 293 (96%) as White. Blacks were less likely to be discharged home
(42.4% vs 58.9%, P < .0001) and had lower repeat operation rates (6.81% vs 11.5%,
P = .0009); both remained significant in the propensity score-matched comparison.
Finally, Blacks experienced more postoperative complications, higher median
Medicare costs, but lower out-of-pocket expenses (P = .0113). Blacks had higher
rates of diabetes (33.7% vs 21.5%, P < .0001) and obesity (9.92% vs 6.85%, P =
.0074), when compared to Whites, but these comorbidities did not significantly
affect odds of 30-day complications. CONCLUSIONS: Black patients having undergone
lumbar spinal stenosis surgery were more likely to have received fusion at
initial operation, had shorter pre- and postoperative follow-up intervals and
displayed variances in discharge disposition. Reasons for these differences are
not entirely understood; however, educational and socioeconomic factors and
possibly ethnic/cultural biases may have contributed. Racial disparities in
health care continue to be identified and should be further explored in order to
eliminate them.
PMID- 28507887
TI - Effectiveness of Operative and Nonoperative Care for Adult Spinal Deformity:
Systematic Review of the Literature.
AB - STUDY DESIGN: Systematic review. OBJECTIVE: There is a need for synthesizing data
on effectiveness of treatments for patients with adult spinal deformity (ASD) due
to its increasing prevalence and health care costs for these patients. The
objective of this review was to estimate the effectiveness of surgery versus
nonoperative care in patients with ASD. METHODS: A systematic review of articles
in published in English using PubMed between 2005 and 2015. Surgical and
nonsurgical series that reported baseline and follow-up health-related quality of
life measures of patients with ASD with a minimum 2 years of follow-up were
selected. Independent extraction of articles by 2 authors using predefined data
fields, including risk of bias assessment. RESULTS: Surgery significantly reduces
disability, pain, and improves patients' quality of life. The average
postoperative improvement in Oswestry Disability Index was -19.1 (+/-9.0),
Numerical Rating Scale back pain -4.14 (+/-1.38), Numerical Rating Scale leg pain
-3.36 (+/-1.33), Short-Form Health Survey 36-SF36-Physical Component score 11.2
(+/-5.07), and Short-Form Health Survey 36-Mental Component score 9.93 (+/-4.96).
The complication rate ranged from 9.52% to 81.52% (mean = 39.62%), and the need
for revision surgery ranged from 1.72% to 40.0% (mean = 15.71%). The best
existing evidence about nonoperative care of ASD is provided from observational
studies with very high risk of bias. Quantitative analyses of nonsurgical cohorts
did not demonstrate significant changes in quality of life of patients after 2
years of observation. CONCLUSIONS: This data may assist clinicians to counsel
patients, as well as to inform health care providers and policymakers about what
to expect from the treatment for ASD.
PMID- 28507889
TI - Does parental support influence children's active school travel?
AB - Today's 'backseat generation' of children is more often driven to school. Active
school travel (AST) can contribute up to 30% of recommended daily physical
activity. Although governed by a complex set of factors, parents are considered
'gatekeepers' of children's travel mode decisions. Therefore, we investigate the
relationship between parental support and children's AST. Data were from Active
Streets, Active People-Junior (British Columbia, Canada). Children self-reported
travel mode to/from school for 1 week (10 trips). We assessed parental perceived
neighborhood traffic and crime safety (Neighborhood Environmental Walkability
Scale-Youth) and frequency of parental support for AST (0-5 */week). We
investigated the association between daily AST behaviour and parental support
using logistic regression (controlling for age, sex, distance to school and
perceived neighborhood safety). In our sample (n = 179, 11.0 +/- 1.0 years, 59%
girls), 57% reported daily AST and 63% of parents provided daily support.
Bivariate analyses showed AST behaviour was significantly associated with
parental support frequency and parents' perceived safety. In adjusted analysis,
daily parental support remained significantly associated with daily AST (OR 9.0,
95% CI 4.2, 19.7). The relationship between parental support and AST was
independent of noted correlates of AST. Thus, interventions that focus solely on
changes to the built environment may not be enough to encourage AST. Therefore,
interventions that aim to increase AST should involve parents and children in the
planning process.
PMID- 28507888
TI - Spine Stereotactic Body Radiotherapy: Indications, Outcomes, and Points of
Caution.
AB - STUDY DESIGN: A broad narrative review. OBJECTIVES: The objective of this article
is to provide a technical review of spine stereotactic body radiotherapy (SBRT)
planning and delivery, indications for treatment, outcomes, complications, and
the challenges of response assessment. The surgical approach to spinal metastases
is discussed with an overview of emerging minimally invasive techniques. METHODS:
A comprehensive review of the literature was conducted on the techniques,
outcomes, and developments in SBRT and surgery for spinal metastases. RESULTS:
The optimal management of patients with spinal metastases is complex and requires
multidisciplinary assessment from an oncologic team that is familiar with the
shifting paradigm as a consequence of evolving techniques in surgery and
stereotactic radiation, as well as new developments in systemic agents. The
Spinal Instability Neoplastic Score and the epidural spinal cord compression
(Bilsky) grading system are useful tools that facilitate communication among
oncologic team members and can direct management by providing a baseline
assessment of risks prior to therapy. The combined multimodality approach with
"separation surgery" followed by postoperative spine SBRT achieves thecal sac
decompression, improves tumor control, and avoids complications that may be
associated with more extensive surgery. CONCLUSION: Spine SBRT is a highly
effective treatment that is capable of delivering ablative doses to the target
while sparing the critical organs-at-risk, chiefly the critical neural tissues,
within a short and manageable schedule. At the same time, surgery occupies an
important role in select patients, particularly with the expanding availability
and expertise in minimally invasive techniques. With rapid adoption of spine SBRT
in centers outside of the academic setting, it is imperative for the practicing
oncologist to understand the relevance and application of these evolving
concepts.
PMID- 28507890
TI - Hand washing with soap and WASH educational intervention reduces under-five
childhood diarrhoea incidence in Jigjiga District, Eastern Ethiopia: A community
based cluster randomized controlled trial.
AB - Despite the tremendous achievement in reducing child mortality and morbidity in
the last two decades, diarrhoea is still a major cause of morbidity and mortality
among children in many developing countries, including Ethiopia. Hand washing
with soap promotion, water quality improvements and improvements in excreta
disposal significantly reduces diarrhoeal diseases. The objective of this study
was to evaluate the effect of hand washing with soap and water, sanitation and
hygiene (WASH) educational Intervention on the incidence of under-five children
diarrhoea. A community-based cluster randomized controlled trial was conducted in
24 clusters (sub-Kebelles) in Jigjiga district, Somali region, Eastern Ethiopia
from February 1 to July 30, 2015. The trial compared incidence of diarrhoea among
under-five children whose primary caretakers receive hand washing with soap and
water, sanitation, hygiene educational messages with control households.
Generalized estimating equation with a log link function Poisson distribution
family was used to compute adjusted incidence rate ratio and the corresponding
95% confidence interval. The results of this study show that the longitudinal
adjusted incidence rate ratio (IRR) of diarrhoeal diseases comparing
interventional and control households was 0.65 (95% CI 0.57, 0.73) suggesting an
overall diarrhoeal diseases reduction of 35%. The results are similar to other
trials of WASH educational interventions and hand washing with soap. In
conclusion, hand washing with soap practice during critical times and WASH
educational messages reduces childhood diarrhoea in the rural pastoralist area.
PMID- 28507891
TI - Discordance in perceived risk and epidemiological outcomes of prostate cancer
among African American men.
AB - As guidelines for prostate cancer screening have changed from an annual screening
recommendation starting at age 50 to discussing the benefits and harms of
screening with health care providers, it is necessary to examine other types of
factors that are important to prostate cancer screening decisions among African
American men. Perceived risk of developing cancer has been shown to predict
cancer control behaviors and is lower among African Americans. We characterized
perceived risk of developing prostate cancer among African American men from
November 2009 to 2011 and evaluated the relationship between prostate cancer risk
perceptions and sociodemographic characteristics, health care experiences, and
knowledge and exposure to health information about cancer. Chi square tests and
logistic regression were employed to determine independent associations. Overall,
men did not believe they were at increased risk of developing prostate cancer;
they believed their risk was equivalent to or lower than men the same age.
Perceived risk of prostate cancer was associated with income (OR = 0.59, 95% CI =
0.26, 1.34, p = 0.03), hypertension (OR = 2.68, 95% CI = 1.17, 6.16, p = 0.02),
and beliefs about the association between race and cancer risk (OR = 2.54, 95% CI
= 1.24, 5.20, p = 0.01). Clinic and community-based approaches to improve
prostate cancer risk comprehension among African American men are needed to
reduce the discordance between perceived risk and epidemiological data on
prostate cancer risk factors. Risk education interventions that are developed for
African American men may need to integrate information about susceptibility for
multiple diseases as well as address strategies for risk reduction and
prevention, and chronic disease management.
PMID- 28507893
TI - Delayed diagnosis of severe tuberculous spondylodiscitis in an asylum seeker;
patient or doctors delay?
AB - The still increasing global migration affects the epidemiology of tuberculosis
(TB) in European countries. We present the case of an asylum seeker from a TB
high-endemic country, who presented with severe TB spondylodiscitis and need for
emergency surgery. The patient had a history of recurrent sterile axillary and
perianal abscesses for years, but TB was never properly ruled out. The patient
underwent surgery, responded well to antibiotics and regained the ability to
walk. After 6 month of treatment the patient was lost to follow-up. In light of
the increasing migration from TB high-endemic countries to low-endemic countries,
this case illustrates the paramount importance of minding TB as a differential
diagnosis.
PMID- 28507892
TI - A case of massive hemoptysis following transesophageal echocardiogram.
AB - INTRODUCTION: Tracheal intubation leading to injury of the airway is a rare
complication of transesophageal echocardiography (TEE). Tracheal trauma is not a
described complication of TEE, and safety literature for this procedure remains
silent on the matter. We describe the case of a patient on systemic
anticoagulation and antiplatelet therapy who underwent TEE and suffered massive
hemoptysis requiring bronchial artery embolization (BAE). CASE PRESENTATION: An
elderly patient was admitted to the hospital with recently diagnosed atrial
fibrillation and shortness of breath. The patient underwent a TEE with successful
synchronized cardioversion on hospital day #2. Later that day the patient
experienced respiratory distress and hemoptysis and was intubated. Oropharyngeal
and gastrointestinal sources of bleeding were excluded. A bronchoscopy revealed
active bleeding from an ulceration in the bronchus intermedius (BI) of the right
lung. A 7 French Arndt endobronchial blocker (Cook Medical, Bloomington, Indiana)
was placed and anticoagulation reversed. Bleeding stopped for two days, but then
returned on hospital day #5, requiring BAE to the right bronchial artery. The
procedure was successful, the patient was successfully extubated, and was
discharged over the next 10 days. DISCUSSION: Massive hemoptysis and respiratory
compromise as a result of tracheal trauma is not described in the TEE literature.
This patient proved to be a difficult esophageal intubation secondary to a newly
discovered Zenker's diverticulum. The risk for bleeding in this patient was
higher secondary to anticoagulation with warfarin and antiplatelet therapy with
ticagrelor. As in all cases of massive hemoptysis, key aspects of care in this
case involved localization of bleeding, reversal of anticoagulation, and
definitive management such as BAE. CONCLUSIONS: Tracheal trauma is not a
described complication of TEE, but clinicians should be mindful of this possible
complication in patients receiving anticoagulation. Typical management for
massive hemoptysis was successful in this patient.
PMID- 28507894
TI - Re-administration of abatacept for the control of articular symptoms of
rheumatoid arthritis during anti-tuberculous therapy.
AB - This case report describes the re-administration of abatacept to successfully
reduce the articularsymptoms of a patient with rheumatoid arthritisduring the
intensive phase of anti-tuberculous therapy. A 75-year-old man developed active
pulmonary tuberculosis during the administration of abatacept for rheumatoid
arthritis. The patient experienced a paradoxical reaction and exacerbation of
rheumatoid arthritis that caused us to discontinue the abatacept. Later re
administration of abatacept along with anti-tuberculosis treatment led to well
controlled rheumatoid arthritis without exacerbation of the tuberculosis. This
case shows that re-administration of abatacept may be much safer than TNF
inhibitor to treat patients who are infected with mycobacteria during
thetreatment of immunological diseases such asrheumatoid arthritiswith biological
agents.
PMID- 28507897
TI - Comparative analysis of microbial diversity in two hot springs of Bakreshwar,
West Bengal, India.
AB - Various aspects of hot springs at Bakreshwar (Lat. 23 degrees 52'48"N; Long. 87
degrees 22'40"E) in West Bengal, India have been investigated since the middle of
20th century, but comprehending the complete diversity and the complexity of the
microbial population therein has been in the continuing process. Some of these
microorganisms are found to have immense industrial importance. Microbes
generally exist in milieus of varying complexities and diversities. Attempting
the usually employed cultivation-based techniques in experimentation with those
microbes had confronted various limitations. To overcome these limitations a
strategy based on high-throughput sequencing of 16S rRNA gene amplicon analysis
was employed for studying the differential diversity and the detailed nature of
microbial population of the two hot springs of Bakreshwar (54 degrees C & 65
degrees C). Paired-end libraries of amplified V-3 hyper-variable 16S rDNA
fragments from sets of samples that varied in their contents, ranging from a
single bacterium to highly complex communities were sequenced. The comparison
revealed the differential aspects in the two hot spring waters; the samples at 54
degrees C showed the bacterial phylum Firmicutes (65.85%) and Synergistetes
(27.24%) predominating and those from hot spring water at 65 degrees C showed
the abundance of the phyla Firmicutes (96.10%) and Proteobacteria (3.36%). The
presence of Archaea in the hot springs could not be ascertained.
PMID- 28507896
TI - Intraoperative resection control using arterial spin labeling - Proof of concept,
reproducibility of data and initial results.
AB - OBJECTIVES: Intraoperative magnetic resonance imaging is a unique tool for
visualizing structures during resection and/or for updating any kind of
neuronavigation that might be hampered as a result of brain shift during surgery.
Advanced MRI techniques such as perfusion-weighted imaging have already proven to
be important in the initial diagnosis preoperatively, but can also help to
differentiate between tumor and surgically induced changes intraoperatively.
Commonly used methods to visualize brain perfusion include contrast agent
administration and are therefore somewhat limited. One method that uses blood as
an internal contrast medium is arterial spin labeling (ASL), which might
represent an attractive alternative. MATERIALS AND METHODS: Ten healthy
volunteers were examined using three different scanners and coils within 1 h (3T
Achieva MRI using 32-channel head coil, 1.5T Achieva MRI using a 6-channel head
coil, 1.5 Intera Scanner using 2 surface coils, Philips, Best, The Netherlands)
and quantitative CBF values were calculated and compared between the different
setups. Additionally, in eight patients with glioblastoma multiforme, ASL was
used pre-, intra-, and postoperatively to define tumor tissue and the extent of
resection in comparison to structural imaging. RESULTS: A high correlation (r =
0.91-0.96) was found between MRI scanners and coils used. ASL was as reliable as
conventional MR imaging if complete resection was already achieved, but
additionally provided valuable information regarding residual tumor tissue in one
patient. CONCLUSIONS: Intraoperative arterial spin-labeling is a feasible,
reproducible, and reliable tool to map CBF in brain tumors and seems to give
beneficial information compared to conventional intraoperative MR imaging in
partial resection.
PMID- 28507895
TI - Diverging volumetric trajectories following pediatric traumatic brain injury.
AB - Traumatic brain injury (TBI) is a significant public health concern, and can be
especially disruptive in children, derailing on-going neuronal maturation in
periods critical for cognitive development. There is considerable heterogeneity
in post-injury outcomes, only partially explained by injury severity.
Understanding the time course of recovery, and what factors may delay or promote
recovery, will aid clinicians in decision-making and provide avenues for future
mechanism-based therapeutics. We examined regional changes in brain volume in a
pediatric/adolescent moderate-severe TBI (msTBI) cohort, assessed at two time
points. Children were first assessed 2-5 months post-injury, and again 12 months
later. We used tensor-based morphometry (TBM) to localize longitudinal volume
expansion and reduction. We studied 21 msTBI patients (5 F, 8-18 years old) and
26 well-matched healthy control children, also assessed twice over the same
interval. In a prior paper, we identified a subgroup of msTBI patients, based on
interhemispheric transfer time (IHTT), with significant structural disruption of
the white matter (WM) at 2-5 months post injury. We investigated how this
subgroup (TBI-slow, N = 11) differed in longitudinal regional volume changes from
msTBI patients (TBI-normal, N = 10) with normal WM structure and function. The
TBI-slow group had longitudinal decreases in brain volume in several WM clusters,
including the corpus callosum and hypothalamus, while the TBI-normal group showed
increased volume in WM areas. Our results show prolonged atrophy of the WM over
the first 18 months post-injury in the TBI-slow group. The TBI-normal group shows
a different pattern that could indicate a return to a healthy trajectory.
PMID- 28507899
TI - Unusual embolization of a pacemaker lead fragment during lead extraction.
PMID- 28507900
TI - Direct visualization of an atrial transseptal left ventricular endocardial lead
implantation within an isolated heart.
PMID- 28507898
TI - Optically and acoustically triggerable sub-micron phase-change contrast agents
for enhanced photoacoustic and ultrasound imaging.
AB - We demonstrate a versatile phase-change sub-micron contrast agent providing three
modes of contrast enhancement: 1) photoacoustic imaging contrast, 2) ultrasound
contrast with optical activation, and 3) ultrasound contrast with acoustic
activation. This agent, which we name 'Cy-droplet', has the following novel
features. It comprises a highly volatile perfluorocarbon for easy versatile
activation, and a near-infrared optically absorbing dye chosen to absorb light at
a wavelength with good tissue penetration. It is manufactured via a 'microbubble
condensation' method. The phase-transition of Cy-droplets can be optically
triggered by pulsed-laser illumination, inducing photoacoustic signal and forming
stable gas bubbles that are visible with echo-ultrasound in situ. Alternatively,
Cy-droplets can be converted to microbubble contrast agents upon acoustic
activation with clinical ultrasound. Potentially all modes offer extravascular
contrast enhancement because of the sub-micron initial size. Such versatility of
acoustic and optical 'triggerability' can potentially improve multi-modality
imaging, molecularly targeted imaging and controlled drug release.
PMID- 28507901
TI - Use of intracardiac echocardiography as a guide during interventricular septum
puncture in a patient undergoing cardiac resynchronization therapy.
PMID- 28507902
TI - An unusual ICD shock: What is the mechanism?
PMID- 28507903
TI - High-output heart failure due to subclavian vessel fistula as a late complication
following implantation of a biventricular pacemaker.
PMID- 28507904
TI - Electroanatomical voltage mapping of atrial Mahaim potentials to guide catheter
ablation.
PMID- 28507905
TI - Gastric syphilis.
AB - Syphilis is a chronic systemic infectious disease. Gastric involvement is
uncommon. We report of a 55-year-old female patient with a history of epigastric
pain and a diagnosis of Syphilis confirmed by main clinical symptoms, tolulized
red unheated serum test(TRUST) and treponema pallidum hemagglutination
assay(TPHA). At the same time, we still reported gastric involvement about
syphilis in this patient with gastroscopy and pathology.
PMID- 28507907
TI - Effectiveness of enzyme replacement therapy in Fabry disease: Long term
experience in Argentina.
AB - : Evidence regarding long term effectiveness of enzyme replacement therapy (ERT)
in Fabry disease (FD) is needed. The aim of this study was to analyze in a cohort
of FD patients in Argentina, the long term effectiveness of ERT on renal, cardiac
and cerebrovascular parameters. METHODS: Patients with genetically proven FD were
included from GADYTEF (Argentinean group for the treatment of FD) between 2001
and 2014. Renal, cardiac, and cerebral outcomes were prospectively studied in
patients treated with ERT. Additionally, the occurrence of major cardiac
complications, stroke, end-stage renal disease and death was analyzed during
follow up. RESULTS: During the follow-up 8 major complications occurred in 5
patients (n = 2 deaths, n = 4 cases of end stage renal disease and n = 1 atrial
fibrillation), 4 of them males and only 1 female who suffered an atrial
fibrillation. Sudden death or stroke did not occur. Four (40%) of 10 males with
baseline left ventricular hypertrophy (LVH) reduced left ventricular mass index
(LVMI) from 163.1 +/- 64.7 to 123.4 +/- 49.8 g/m2, 2 stabilized LVMI and 4
increased LVMI from157.9 +/- 32.3 to 261.6 +/- 48.6 g/m2. Estimated glomerular
filtration was stable in 30 patients (17 males and 13 females). CONCLUSIONS: We
observed a few major complications during the follow up. Future studies are
necessary to show the effectiveness of ERT in affected patients.
PMID- 28507906
TI - A case of a positive coccidioides stool culture in an immunocompetent patient
with disseminated coccidioidomycosis.
AB - Coccidioidomycosis (CM) is an infection caused by the coccidioides fungus. The
spectrum of the disease ranges from a mild upper respiratory illness to severe
disseminated infection that could affects the bones, joints, skin, central
nervous system, and the gastrointestinal tract. Previous reports of a positive
stool culture in the setting of disseminated CM are extremely rare. Herein, we
describe a case of a 43-year-old immunocompetent patient with disseminated CM and
evidence of positive coccidioides stool culture.
PMID- 28507908
TI - Renal Cell Carcinoma in a Pregnant Woman With Horseshoe Kidney.
AB - To our knowledge, this is the first reported case of renal cell carcinoma in
kidney horseshoe diagnosed in the second trimester of pregnancy. We performed
open radical nephrectomy when the pregnancy was completed. Kidney cancer is rare
during pregnancy and the symptoms can be mimic urinary infection. The diagnosis
and its management can be a challenge.
PMID- 28507909
TI - Open Vesicocalicostomy for the Management of Transplant Ureteral Stricture.
AB - A 59-year-old male developed a proximal stricture of his transplant ureter ten
years after a living donor renal transplant. Endoscopic management was
unsuccessful, and the patient was temporized with percutaneous nephrostomy tubes
for months. Eventually, it became clear he would require surgical revision.
Intraoperatively, complete fibrosis of the renal hilum, and intrarenal location
of the pelvis precluded the planned pyelovesicostomy. A successful open
vesicocalicostomy was performed, anastomosing a bladder flap to a lower pole
calix. The patient remains recurrence free after 6 months of follow-up.
PMID- 28507910
TI - Penile Calciphylaxis: The Use of Radiological Investigations in the Management of
a Rare and Challenging Condition.
AB - Penile calciphylaxis is a rare phenomenon of penile necrosis observed in patients
with hemodialysis-dependent end-stage renal failure. Multiple treatments have
been proposed including conservative management, surgical debridement and
penectomy; yet, the prognosis remains extremely poor. Here, we describe a patient
with protracted resolution of dry gangrene of the glans, which failed
conservative management of wound care and pain management. Radiological studies
revealed extensive calcification of abdominal aorta and branching vessels
including the penile arteries. Due to intolerable pain, the patient required
total penectomy. Earlier surgical intervention guided by findings on radiological
studies may improve quality of life in this population.
PMID- 28507911
TI - Filariasis Orchitis-Differential for Acute Scrotum Pathology.
AB - Granulomatous Orchitis secondary to lymphatic filiarisis is a rare diagnosis
within the United States. We report a case of a 22yo Male from Sri Lanka, with a
new onset scrotal swelling and palpable right testicular mass. Ultrasound
identified a 1 cm right testicular mass with signs of tunica albuginea invasion.
A right inguinal radical orchiectomy was performed and pathology showed Filarial
orchitis. This report describes the detailed history, physical exam, and
diagnostic workup and treatment options for a rare entity for acute scrotal
pathology.
PMID- 28507912
TI - Preparation, characterization and antibacterial activity of chitosan and
phosphorylated chitosan from cuttlebone of Sepia kobiensis (Hoyle, 1885).
AB - Chitosan is a commercially available derivative of chitin that has been
extensively studied for its antimicrobial properties. In order to improve the
water solubility and its biological activity, the chemical modification or
derivatisation is attempted. In the present investigation, the chitosan prepared
from the cuttlebone of Sepia kobiensis was being chemically modified by reacting
it with orthophosphoric acid so as to obtain phosphorylated chitosan. Then the
chitosan and phosphorylated chitosan were structurally characterized through FT
IR spectroscopy. Further the antibacterial activity of chitosan and
phosphorylated chitosan was tested against clinically isolated human pathogens
(Gram-positive: Streptococcus sp., Streptococcus pneumoniae and Staphylococcus
aureus and Gram-negative: Escherichia coli, Vibrio cholerae, V. alginolyticus,
Vibrio parahaemolyticus, Pseudomonas aeruginosa, Klebsiella pneumoniae,
Salmonella sp. and Proteus vulgaris) by well diffusion method and the Minimum
Inhibitory Concentration (MIC) was also calculated. The results of the present
study suggests that the chitosan and phosphorylated chitosan has concentration
dependent antibacterial activity with variation against several pathogenic human
pathogenic bacterial strains which indicates their possible use as antibacterial
agents.
PMID- 28507915
TI - Smoking in Renal Transplantation; Facts Beyond Myth.
AB - Smoking is one of the preventable leading causes of death worldwide. Most of the
studies focused on the association between smoking and cardiovascular disease,
pulmonary diseases, malignancy and death. However, the direct effect of smoking
on the renal system was undermind. There are emerging evidence correlating
tobacco use with pathological changes in the normal kidneys. The effect is more
obvious on the renal allograft most probably due to the chronic immune
suppression status and the metabolic effect of the drugs. Several studies have
documented a deleterious effect of smoking on the renal transplant recipients.
Smoking was associated with lowering patient and graft survival. Smoking
cessation proved to improve graft survival and to a lesser extent recipient
survival. Even receiving a renal transplant from a smoker donor increases the
risk of death for the recipient and carries a poorer graft survival compared to
non-smoking donors. Most of the studies investigating the effect of smoking were
based on self-reporting questioners, which may be misleading due to poor recall
or the desire to give socially acceptable answers. This made the need of a
reliable biomarker of ultimate importance. Cotinine was proposed as a promising
biomarker that may help to provide objective evidence regarding the status of
smoking and the dose of nicotine exposure, yet there are still some limitations
of its use. The aim of this work is to review the current evidence to improve our
understanding of this critical topic. Indeed, this will help to guide better
designed studies in the future.
PMID- 28507913
TI - Role of gastroesophageal reflux disease in lung transplantation.
AB - Lung transplantation is one of the highest risk solid organ transplant
modalities. Recent studies have demonstrated a relationship between
gastroesophageal reflux disease (GERD) and lung transplant outcomes, including
acute and chronic rejection. The aim of this review is to discuss the
pathophysiology, evaluation, and management of GERD in lung transplantation, as
informed by the most recent publications in the field. The pathophysiology of
reflux-induced lung injury includes the effects of aspiration and local
immunomodulation in the development of pulmonary decline and histologic
rejection, as reflective of allograft injury. Modalities of reflux and esophageal
assessment, including ambulatory pH testing, impedance, and esophageal manometry,
are discussed, as well as timing of these evaluations relative to
transplantation. Finally, antireflux treatments are reviewed, including medical
acid suppression and surgical fundoplication, as well as the safety, efficacy,
and timing of such treatments relative to transplantation. Our review of the data
supports an association between GERD and allograft injury, encouraging a strategy
of early diagnosis and aggressive reflux management in lung transplant recipients
to improve transplant outcomes. Further studies are needed to explore additional
objective measures of reflux and aspiration, better compare medical and surgical
antireflux treatment options, extend follow-up times to capture longer-term
clinical outcomes, and investigate newer interventions including minimally
invasive surgery and advanced endoscopic techniques.
PMID- 28507916
TI - Past, present and future of kidney paired donation transplantation in India.
AB - One third of healthy willing living kidney donors are rejected due to ABO blood
group incompatibility and donor specific antibody. This increases pre-transplant
dialysis duration leading to increased morbidity and mortality on the kidney
transplantation waiting list. Over the last decade kidney paired donation is most
rapidly increased source of living kidney donors. In a kidney transplantation
program dominated by living donor kidney transplantation, kidney paired donation
is a legal and valid alternative strategy to increase living donor kidney
transplantation. This is more useful in countries with limited resources where
ABO incompatible kidney transplantation or desensitization protocol is not
feasible because of costs/infectious complications and deceased donor kidney
transplantation is in initial stages. The matching allocation, ABO blood type
imbalance, reciprocity, simultaneity, geography were the limitation for the
expansion of kidney paired donation. Here we describe different successful ways
to increase living donor kidney transplantation through kidney paired donation.
Compatible pairs, domino chain, combination of kidney paired donation with
desensitization or ABO incompatible transplantation, international kidney paired
donation, non-simultaneous, extended, altruistic donor chain and list exchange
are different ways to expand the donor pool. In absence of national kidney paired
donation program, a dedicated kidney paired donation team will increase access to
living donor kidney transplantation in individual centres with team work. Use of
social networking sites to expand donor pool, HLA based national kidney paired
donation program will increase quality and quantity of kidney paired donation
transplantation. Transplant centres should remove the barriers to a broader
implementation of multicentre, national kidney paired donation program to further
optimize potential of kidney paired donation to increase transplantation of O
group and sensitized patients. This review assists in the development of similar
programs in other developing countries.
PMID- 28507914
TI - Intra-islet endothelial cell and beta-cell crosstalk: Implication for islet cell
transplantation.
AB - The intra-islet microvasculature is a critical interface between the blood and
islet endocrine cells governing a number of cellular and pathophysiological
processes associated with the pancreatic tissue. A growing body of evidence
indicates a strong functional and physical interdependency of beta-cells with
endothelial cells (ECs), the building blocks of islet microvasculature. Intra
islet ECs, actively regulate vascular permeability and appear to play a role in
fine-tuning blood glucose sensing and regulation. These cells also tend to behave
as "guardians", controlling the expression and movement of a number of important
immune mediators, thereby strongly contributing to the physiology of islets. This
review will focus on the molecular signalling and crosstalk between the intra
islet ECs and beta-cells and how their relationship can be a potential target for
intervention strategies in islet pathology and islet transplantation.
PMID- 28507917
TI - Systemic meta-analysis assessing the short term applicability of early conversion
to mammalian target of rapamycin inhibitors in kidney transplant.
AB - AIM: To consolidate the present evidence of effectiveness in renal functioning
and graft survival following early introduction of mammalian target of rapamycin
(mTOR) inhibitors with or without calcineurin inhibitors (CNIs) in renal
transplant recipients. METHODS: We analysed the current literature following
PROSPERO approval describing the role of immunosuppressive agent, mTOR inhibitors
as an alternative to CNI within six months of renal transplant by searching the
PubMed, EMBASE, Cochrane, Crossref, and Scopus using MeSH terms. RESULTS: Six
articles of early withdrawal of CNI and introduction of mTOR-inhibitors within
six months of renal transplantation were sought. Glomerular filtration rate (GFR)
and serum creatinine were significantly better in mTOR inhibitor group with
equivalent survival at 12 mo, even though Biopsy Proven Acute rejection was
significantly higher in mTOR-inhibitor group. CONCLUSION: The evidence reviewed
in this meta-analysis suggests that early introduction mTOR-inhibitors
substantial CNI minimization. The mTOR inhibitors such as everolimus and
sirolimus, due to their complementary mechanism of action and favourable
nephrotoxicity profile; better glomerular filtration, lower serum creatinine with
equivalent survival. Having said that, due to the higher rejection rate, may
influence the use of these regimens to patients with moderate to high
immunological risk patients.
PMID- 28507918
TI - Living related and living unrelated kidney transplantations: A systematic review
and meta-analysis.
AB - AIM: To compare the outcomes between related and unrelated kidney
transplantations. METHODS: Literature searches were performed following the
Cochrane guidelines. We conducted a systematic review and a meta-analysis, which
included 12 trials that investigated outcomes including the long-term (ten
years), mid-term (one to five years), and short-term (one year) graft survival
rate as well as the acute rejection rate. Meta-analyses were performed using
fixed and random-effects models, which included tests for publication bias and
heterogeneity. RESULTS: No difference in graft survival rate was detected in
patients who underwent living related kidney transplantations compared to
unrelated (P = 0.44) transplantations after ten years. There were no significant
differences between the graft survival rate in living related and unrelated
kidney transplantations after a short- and mid-term follow-up (P = 0.35, P =
0.46). There were no significant differences between the acute rejection rate in
living related and unrelated kidney transplantations (P = 0.06). CONCLUSION: The
long, mid and short term follow-up of living related and unrelated kidney
transplantation showed no significant difference in graft survival rate. Also,
acute rejection rate was not significantly different between groups.
PMID- 28507919
TI - Hepatitis C Virus RNA Strands Detection in Peripheral Blood Mononuclear Cells
Legitimizes Virus Eradication in Negative Serum PCR Naive and Post-treatment
Patients.
AB - Background and Aims: Hepatitis C virus (HCV) hepatotropism is associated with
intra-peripheral blood mononuclear cell (PBMC) infection that causes post
treatment relapse in RNA seronegative patients. Our understanding of the
association of non-viremic hepatic fibrosis with positive anti-HCV IgG antibodies
and active hepatocellular damage might be increased by PBMCs screening for
intracellular infection. Thus, the goals of this study included evaluation of
PBMCs PCR for diagnosing HCV infection, addressing PBMCs plus serum real-time
(SRT) PCR benefits over SRT-PCR alone, studying intra-PBMCs distribution of RNA
sense and antisense strands, and identifying treatment feasibility in solitary
intracellular infection. Methods: Enzyme-linked immunosorbent assay, SRT-PCR and
PBMCs PCR were used to evaluate HCV infection in 401 subjects. The patients were
classified into groups of negative controls (n = 30), positive controls (n = 63),
non-viremia post-treatment (experienced; n = 166) and naive (n = 49) cases, and
non-viremia positive PBMCs PCR naive (n = 35) and experienced (n = 58) patients.
Results: The diagnosis of true positive and negative by PBMCs PCR and SRT-PCR had
100% and 96.7% compatibility respectively. PBMCs PCR detected intracellular HCV
infection in 49 out of 215 non-viremia patients; among them, naive cirrhotics had
significantly higher number of intracellular infection than the naive non
cirrhotic (p < 0.001) and experienced patients (p < 0.0001). Antisense and sense
strands were respectively recognized in naive and experienced cases (p =
0.01218). Intracellular HCV strands were detected in 18.02% of experienced
patients. Recognition of intracellular RNA strands showed significant decline in
experienced compared to naive patients (p < 0.05). Conclusion: PBMCs PCR is a
valid diagnostic test that can diagnose intracellular HCV when SRT-PCR is
negative. Antisense and sense strands are respectively recognized more often in
naive and experienced patients. The expected overall relapsing rate in our cohort
was 18.02%. Intra-PBMC infections are associated with liver cirrhosis in naive
non-viremia patients. Eradication of intracellular strands is recommended to
avoid RNA seroconversion. Ethical approval certificate: Registration number
10231.
PMID- 28507920
TI - Passenger Lymphocyte Syndrome (PLS): A Single-center Retrospective Analysis of
Minor ABO-incompatible Liver Transplants.
AB - Background and Aims: Due to the shortage of donor livers, minor ABO-incompatible
liver transplantations are commonly performed. Together with the allograft,
immunocompetent B-lymphocytes, called passenger lymphocytes, are transplanted. In
case of minor ABO-incompatibility, these passenger lymphocytes produce antibodies
directed towards the recipient's red blood cells, which causes immune-mediated
hemolysis, also known as the passenger lymphocyte syndrome (PLS). Although this
is a self-limiting disorder, serious complications can occur, including graft
failure. Retrospectively, we evaluated the role of PLS in minor ABO-incompatible
liver transplantations performed at our center. Methods: A retrospective analysis
was conducted for all minor ABO-incompatible liver transplantations performed at
the Antwerp University Hospital between 2003 and 2015. All patient files were
inspected for clinical and laboratory findings. In cases of PLS diagnosis, the
applied treatment was also studied. Results: In total, 10 patients underwent a
minor ABO-incompatible liver transplantation and 4 showed signs of PLS. All 4 PLS
patients were treated with different therapeutic strategy, corresponding to the
severity of hemolysis. In all 4 cases, PLS resolved following treatment.
Conclusion: When performing minor ABO-incompatible liver transplantations,
knowledge of PLS is elemental. Next to a high index of clinical suspicion, we
suggest routine screening for markers of hemolysis, with emphasis on haptoglobin
level and direct antiglobulin test, weekly in the first 4 weeks post
transplantation as well as in case of a sudden hemoglobin drop within the first 3
months after transplantation. Peri- and postoperative transfusion support using
donor-compatible blood has been suggested to prevent the occurrence or limit the
extent of hemolysis.
PMID- 28507921
TI - Sofosbuvir-based Regimens with Task Shifting Is Cost-effective in Expanding
Hepatitis C Treatment Access in the United States.
AB - Background and Aims: The current paradigm of specialist physician-managed
treatment of chronic hepatitis C virus infection (HCV) is inefficient in
absorbing the approximately 3 million patients awaiting treatment in the United
States. Task shifting-whereby specialist physicians screen patients for treatment
eligibility but on-treatment monitoring is devolved to more abundant non
physician clinicians-achieves non-inferior treatment outcomes with second
generation direct-acting antivirals (2nd Gen DAAs), may increase treatment
capacity, and may facilitate greater treatment access. We determined the cost
effectiveness of 2nd Gen DAAs with respect to interferon-based first-generation
DAAs (1st Gen DAAs) within a task-shifted treatment model. Methods: Using a
previously described decision-analytic Markov structure, we modeled a
hypothetical cohort of 1,000 patients with HCV genotype 1 infection over a
lifetime horizon, based upon our outreach clinic's HCV treatment protocol.
Treatment-naive and treatment-experienced HCV cohorts were modeled separately,
based upon our outr8each clinic's demographics. Treatment response to 2nd Gen
DAAs was modeled based on our outreach clinic's data. Adverse events, utility,
costing, and transition probabilities were sourced from the literature. Results:
Driven by improved effectiveness and safety, as well as an expected increase in
treatment capacity, 2nd Gen DAAs treatment monitored by non-physician clinicians
was projected to improve health outcomes and be dominant from a cost-effective
perspective versus that of 1st Gen DAAs. Trends were consistent across all
assessed patient subpopulations. Conclusions: Based on an assumption of increased
treatment capacity accompanying a task-shifted treatment model, 2nd Gen DAAs
based treatment was cost effective and cost saving as compared to 1st Gen DAAs
based treatment for all HCV patient subgroups assessed.
PMID- 28507922
TI - Sofosbuvir Use in the Setting of End-stage Renal Disease: A Single Center
Experience.
AB - Background and Aims: Patients with chronic hepatitis C (CHC) and end-stage renal
disease (ESRD) who are dialysis-dependent form a unique group, in which safety,
tolerability and efficacy of sofosbuvir (SOF)-based direct-acting antivirals
(DAAs) need further evaluation. Methods: We performed a retrospective analysis of
14 patients with CHC and ESRD on dialysis who received 15 courses of SOF-based
therapy. We evaluated dose escalation to standard-dose SOF in this proof-of
principle experience. Results: Sustained virological response (defined as
undetectable viral load at 12 weeks, SVR-12) was achieved in 13 out of the 15
(86.7%) treatment courses. Seven (46.6%) patients received reduced half dose as
conservative proof-of-principal to mitigate potential toxicity. In 13 out of 15
treatment courses, patients completed the designated treatment duration. One
patient was treated twice and developed SVR-12 with the retreatment. One patient
was lost to follow-up and counted as a non-responder. Premature discontinuations
were not due to DAA-related adverse effects. There were no reports of severe
adverse effects or drug interactions. Conclusion: We treated CHC patients with
ESRD using dose escalation to standard-dose SOF in this proof-of-principle
experience and achieved SVR rates comparable to general population.
PMID- 28507923
TI - Phenotypes and Chronic Organ Damage May Be Different among Siblings with Wilson's
Disease.
AB - Background and Aims: Cloning of ATP7B provided evidence that Wilson's disease is
a hepatic copper toxicosis with a variety of extrahepatic complications. Affected
siblings with the same genetic background and exposure to similar environmental
factors may be a good model for the study of genotype-phenotype correlation.
Methods: Twenty-three affected siblings in 11 families were selected from a
database. The first phenotypes were determined according to the international
proposal. The final types of chronic organ damage were re-evaluated for life-long
management. Results: Phenotypes were identical in 5 of the families and different
in 6 of the families. The acute hepatic phenotype H1 was found in 3 younger
siblings and 1 older sibling. All survived an acute episode of hemolysis with
underlying chronic liver disease. One also presented complication with
neurological disease. The neurological phenotype N1 with neuropsychiatric
symptoms and hepatic disease was found in 2 aged siblings of 1 family, in an
older sibling in 3 families and in the oldest sibling in 1 family. Phenotypes in
siblings were mainly split by either H1 occurring in random order or age
dependent N1. Types of chronic organ damage were identical in 8 of the families
and different in 3 of the families. The same combination of chronic liver disease
was found in 6 families and chronic liver disease complicated with neurological
disease in 2 families. Split organ damage in siblings was found when an older
sibling was complicated by neurological disease. There was no reverse combination
of a younger sibling being complicated by neurological disease in any of the
families. Conclusion: Phenotype combinations of siblings were mainly modified by
externally-induced hemolytic episodes, while chronic organ damage in siblings was
split by age-dependent neurological complications.
PMID- 28507924
TI - Improved Outcomes Following Hepatocellular Carcinoma (HCC) Diagnosis in Patients
Screened for HCC in a Large Academic Liver Center versus Patients Identified in
the Community.
AB - Background and Aims: Hepatocellular carcinoma (HCC) is the sixth most commonly
occurring cancer worldwide. Knowledge and adherence to HCC surveillance
guidelines has been associated with earlier detection. We sought to evaluate
characteristics and outcomes following HCC diagnosis in patients screened for HCC
in a large academic liver center versus patients diagnosed and referred from the
community. Methods: We reviewed the records of patients diagnosed with HCC in the
liver center of an academic institution from January 1999 till December 2013.
Patients were classified into two groups: patients followed in our hepatology
clinic and patients with HCC recently referred to our center. Univariate analysis
was performed using chi-squared test and multivariate analysis was performed
using SPSS 22.0. Results: The records of 410 patients were reviewed, and included
77.3% of patients referred from the community and 22.7% of patients followed in
our clinic. In the clinic group, 75.6% were identified with one nodule at initial
diagnosis, compared to 65.6% in the referral group. Patients in the referral
group were more likely to present with tumors >=5 cm at diagnosis, with 28.7%
compared to 5.4% in the clinic group (p < 0.0001). Patients referred from the
community were also less likely to undergo transplant, with 32.2% as compared to
48.4% of the clinic group (p < 0.004). Conclusion: Patients with chronic liver
disease managed in an academic liver center present in the early stage of HCC
diagnosis and are more likely to meet the Milan criteria and undergo transplant.
Early referral to a specialized transplant center, if feasible, where a
multidisciplinary approach is utilized might be essential in the management of
chronic liver disease.
PMID- 28507925
TI - Stratified Platelet-to-lymphocyte Ratio: A Novel Target for Prognostic Prediction
of Hepatocellular Carcinoma after Curative Liver Resection.
AB - Background and Aims: Platelet-to-lymphocyte ratio (PLR) has been shown to predict
prognosis of cancers. We aimed to evaluate the prognostic value of stratification
of PLR in patients after curative liver resection (CLR) for hepatocellular
carcinoma (HCC). Methods: A total of 1804 patients who underwent CLR for
suspected HCC between January 2007 and January 2014 were screened for the study.
All of the patients were categorized into equal tertiles according to the number
of patients and the distribution of PLR. Prognostic significance was determined
for overall survival (OS) and was assessed using Kaplan-Meier analysis.
Univariate and multivariate Cox proportional hazard regression analyses were
evaluated for association of all independent parameters with disease prognosis.
Results: The optimal cut-off points of preoperative PLR were: (T1) 11.98-75.00,
(T2) 75.00-113.33 and (T3) 113.33-567.50. There were obvious differences in each
PLR tertile with mortality within 36 months of CLR (plog-rank < 0.001).
Multivariable analysis suggested that the level of PLR (HR = 1.004, 95%CI: 1.001
1.008, p = 0.006), portal vein thrombosis (HR = 3.406, 95%CI: 1.185-9.794, p =
0.023), number of nodules (HR = 1.810, 95%CI: 1.345-2.437, p < 0.001), Child
Turcotte-Pugh score (HR = 1.741, 95%CI: 1.129-2.684, p = 0.012) and microvascular
invasion (HR = 2.730, 95%CI: 1.777-4.196, p < 0.001) were significant predictors
of mortality. Kaplan-Meier analysis of overall survival (OS) demonstrated that
each PLR tertile showed a progressively worse OS and apparent separation (plog
rank = 0.016). The highest 5-year OS rate following CLR (58%) was revealed in
tertile 1. In contrast, the lowest 5-year OS rate (30%) was revealed in tertile
3. Conclusion: Stratified preoperative PLR could strengthen the predictive power
for OS in HCC patients with CLR.
PMID- 28507926
TI - Decrease of Alpha-fetoprotein in Patients with Cirrhosis Treated with Direct
acting Antivirals.
AB - Background and Aims: The lack of specificity has limited the role of serum alpha
fetoprotein (AFP) for hepatocellular carcinoma (HCC) screening among patients
with cirrhosis related to hepatitis C virus (HCV) infection. We sought to examine
whether AFP may decrease after achieving a sustained virological response (SVR)
in patients with HCV-related cirrhosis. Methods: We performed a retrospective
study of patients with HCV-related cirrhosis who were cured with direct-acting
antiviral (DAA) therapy at the University of California, Los Angeles. Laboratory
values, including serum AFP, were measured before and after completing the DAA
treatment. Results: Fifty-six patients met the inclusion criteria, with median
(interquartile range [IQR]) age of 67 (58-69) years and with 51.8% being male.
All patients received DAA therapy without interferon. AFP decreased from median
(IQR) 7.2 (4.2-13.4) ng/mL before DAAs to 4.2 (2.7-6.3) ng/mL at the end of
treatment and 4.2 (2.9-6.8) ng/mL at 12 weeks after treatment (p < 0.001). Model
for end-stage liver disease (MELD), fibrosis-4 (FIB4), and aspartate transaminase
(AST) to platelet ratio index (APRI) scores at baseline were not significantly
associated with AFP reduction. On multivariate analysis, platelet count, AST and
total bilirubin at baseline were significantly correlated to AFP reduction (p =
0.04, 0.009 and 0.04, respectively). The higher the baseline AFP, the greater the
reduction in AFP. There was no statistically significant correlation between
baseline AFP and MELD, FIB4 or APRI scores. Conclusion: There was a significant
decrease in AFP in patients with cirrhosis who achieved a SVR with DAAs. Given a
reduction in AFP after DAA treatment, AFP should be further studied as a
screening modality for HCC in patients with cirrhosis.
PMID- 28507928
TI - The Role of Direct-acting Antivirals in the Treatment of Children with Chronic
Hepatitis C.
AB - In the United States, chronic infection with the hepatitis C virus (HCV) affects
an estimated 0.1-2% of the pediatric population, who are consequently at risk for
major complications, including cirrhosis, hepatocellular carcinoma, and death.
The current standard of treatment for chronic hepatitis C (CHC) in children is
pegylated-interferon-alpha (PEG-IFN) in combination with ribavirin. PEG
IFN/ribavirin therapy is approved for children ages 3 and older; however, it is
often held from use until adulthood because of its extensive list of potential
side effects and high likelihood of causing adverse symptoms. While CHC is
usually indolent in children and adolescents, immediately treating and curbing
the spread of HCV before adulthood is important, as there can be transmission to
other individuals via sexual activity and infected females can later vertically
transmit the infection during pregnancy, the latter representing the most common
means of transmission for children in the United States. The recent development
of direct-acting antivirals has shown promising results in clinical trials for
use in children and has dramatically increased the rates of sustained virological
response in adults while improving side effect profiles as compared to interferon
based treatments. Given the usually indolent course of CHC in children,
significant side effects of the currently-approved PEG-IFN/ribavirin therapy, and
likely availability of all-oral interferon-free regimens for children within a
few years, deferring treatment in clinically-stable children with CHC in
anticipation of upcoming superior treatment modalities may be justified.
PMID- 28507927
TI - Immune Dysfunction in Cirrhosis.
AB - Cirrhosis due to any etiology disrupts the homeostatic role of liver in the body.
Cirrhosis-associated immune dysfunction leads to alterations in both innate and
acquired immunity, due to defects in the local immunity of liver as well as in
systemic immunity. Cirrhosis-associated immune dysfunction is a dynamic
phenomenon, comprised of both increased systemic inflammation and
immunodeficiency, and is responsible for 30% mortality. It also plays an
important role in acute as well as chronic decompensation. Immune paralysis can
accompany it, which is characterized by increase in anti-inflammatory cytokines
and suppression of proinflammatory cytokines. There is also presence of increased
gut permeability, reduced gut motility and altered gut flora, all of which leads
to increased bacterial translocation. This increased bacterial translocation and
consequent endotoxemia leads to increased blood stream bacterial infections that
cause systemic inflammatory response syndrome, sepsis, multiorgan failure and
death. The gut microbiota of cirrhotic patients has more pathogenic microbes than
that of non-cirrhotic individuals, and this disturbs the homeostasis and favors
gut translocation. Prompt diagnosis and treatment of such infections are
necessary for better survival. We have reviewed the various mechanisms of immune
dysfunction and its consequences in cirrhosis. Recognizing the exact
pathophysiology of immune dysfunction will help treating clinicians in avoiding
its complications in their patients and can lead to newer therapeutic
interventions and reducing the morbidity and mortality rates.
PMID- 28507931
TI - Tranilast Can be a Useful Addition to the Limited Anti-Epidermolysis Bullosa
Weaponry.
PMID- 28507930
TI - Non-alcoholic Fatty Liver Disease in South Asians: A Review of the Literature.
AB - Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis
(NASH) are national and global epidemics. The disease is characterized by a
spectrum of liver steatosis (fat deposition), inflammation (in NASH) and
fibrosis. NAFLD and specifically NASH can lead to cirrhosis, which carry risks of
progression to portal hypertension and hepatocellular carcinoma (HCC). NASH is
also associated with higher mortality from cardiovascular causes. Most of the
data for NAFLD has been obtained from the perspective of developed nations,
although the disease is increasing and threatening to reach epidemic proportions
across the world. Emerging data is notable for high prevalence of NAFLD in South
Asian populations, presumably resulting from a combination of underlying genetic
polymorphisms and changes in socio-economic status. It is also notable that an
'Asian Paradox' has been defined for NAFLD based upon the observation of lower
than pre-defined body mass index (BMI), otherwise termed as "lean NAFLD", among
this population. Yet, data remains limited in regards to the characteristics of
NAFLD/NASH in this population. In this article, we present a review of the
literature and discuss the prevalence, associated risk factors and burden of HCC
in South Asians with NAFLD.
PMID- 28507929
TI - Perspectives on Nonalcoholic Fatty Liver Disease: An Overview of Present and
Future Therapies.
AB - Nonalcoholic fatty liver disease (NAFLD) represents a major public health
epidemic. Pharmacologic therapies for this condition are scarce, but multiple
agents with novel mechanisms of action are in development. Here we review the
pathophysiology and natural history of NALFD, diagnostic testing and data for
currently available treatment strategies. We then turn our attention to promising
developmental drugs and their respective trials. As the prevalence of fatty liver
disease increases, clinicians will have more tools at hand for management of this
condition. We conclude the horizon is bright for patients and doctors who deal
with NAFLD.
PMID- 28507932
TI - Application of Various Types of Liposomes in Drug Delivery Systems.
AB - Liposomes, due to their various forms, require further exploration. These
structures can deliver both hydrophilic and hydrophobic drugs for cancer,
antibacterial, antifungal, immunomodulation, diagnostics, ophtalmica, vaccines,
enzymes and genetic elements. Preparation of liposomes results in different
properties for these systems. In addition, based on preparation methods,
liposomes types can be unilamellar, multilamellar and giant unilamellar; however,
there are many factors and difficulties that affect the development of liposome
drug delivery structure. In the present review, we discuss some problems that
impact drug delivery by liposomes. In addition, we discuss a new generation of
liposomes, which is utilized for decreasing the limitation of the conventional
liposomes.
PMID- 28507933
TI - Novel Pentablock Copolymers as Thermosensitive Self-Assembling Micelles for
Ocular Drug Delivery.
AB - Many studies have focused on how drugs are formulated in the sol state at room
temperature leading to the formation of in situ gel at eye temperature to provide
a controlled drug release. Stimuli-responsive block copolymer hydrogels possess
several advantages including uncomplicated drug formulation and ease of
application, no organic solvent, protective environment for drugs, site
specificity, prolonged and localized drug delivery, lower systemic toxicity, and
capability to deliver both hydrophobic and hydrophilic drugs. Self-assembling
block copolymers (such as diblock, triblock, and pentablock copolymers) with
large solubility variation between hydrophilic and hydrophobic segments are
capable of making temperature-dependent micellar assembles, and with further
increase in the temperature, of jellifying due to micellar aggregation. In
general, molecular weight, hydrophobicity, and block arrangement have a
significant effect on polymer crystallinity, micelle size, and in vitro drug
release profile. The limitations of creature triblock copolymers as initial burst
release can be largely avoided using micelles made of pentablock copolymers.
Moreover, formulations based on pentablock copolymers can sustain drug release
for a longer time. The present study aims to provide a concise overview of the
initial and recent progresses in the design of hydrogel-based ocular drug
delivery systems.
PMID- 28507935
TI - Phospholipid Complex Technique for Superior Bioavailability of Phytoconstituents.
AB - Phytoconstituents have been utilized as medicines for thousands of years, yet
their application is limited owing to major hurdles like deficit lipid
solubility, large molecular size and degradation in the gastric environment of
gut. Recently, phospholipid-complex technique has unveiled in addressing these
stumbling blocks either by enhancing the solubilizing capacity or its
potentiating ability to pass through the biological membranes and it also
protects the active herbal components from degradation. Hence, this phospholipid
complex-technique can enable researchers to deliver the phytoconstituents into
systemic circulation by using certain conventional dosage forms like tablets and
capsules. This review highlights the unique property of phospholipids in drug
delivery, their role as adjuvant in health benefits, and their application in the
herbal medicine systems to improve the bioavailability of active herbal
components. Also we summarize the prerequisites for phytosomes preparation like
the selection of type of phytoconstituents, solvents used, various methods
employed in phytosomal preparation and its characterization. Further we discuss
the key findings of recent research work conducted on phospholipid-based delivery
systems which can enable new directions and advancements to the development of
herbal dosage forms.
PMID- 28507936
TI - Thermal Stability and Kinetic Study of Fluvoxamine Stability in Binary Samples
with Lactose.
AB - Purpose: In the present study the incompatibility of FLM (fluvoxamine) with
lactose in solid state mixtures was investigated. The compatibility was evaluated
using different physicochemical methods such as differential scanning calorimetry
(DSC), Fourier-transform infrared (FTIR) spectroscopy and mass spectrometry.
Methods: Non-Isothermally stressed physical mixtures were used to calculate the
solid-state kinetic parameters. Different thermal models such as Friedman, Flynn
Wall-Ozawa (FWO) and Kissinger-Akahira-Sunose (KAS) were used for the
characterization of the drug-excipient interaction. Results: Overall, the
incompatibility of FLM with lactose as a reducing carbohydrate was successfully
evaluated and the activation energy of this interaction was calculated.
Conclusion: In this research the lactose and FLM Maillard interaction was proved
using physicochemical techniques including DSC and FTIR. It was shown that DSC-
based kinetic analysis provides fast and versatile kinetic comparison of
Arrhenius activation energies for different pharmaceutical samples.
PMID- 28507934
TI - The Challenges of Recombinant Endostatin in Clinical Application: Focus on the
Different Expression Systems and Molecular Bioengineering.
AB - Angiogenesis plays an essential role in rapid growing and metastasis of the
tumors. Inhibition of angiogenesis is a putative strategy for cancer therapy.
Endostatin (Es) is an attractive anti-angiogenesis protein with some clinical
application challenges including; short half-life, instability in serum and
requirement to high dosage. Therefore, production of recombinant endostatin (rEs)
is necessary in large scale. The production of rEs is difficult because of its
structural properties and is high-cost. Therefore, this review focused on the
different expression systems that involved in rEs production including;
mammalian, baculovirus, yeast, and Escherichia coli (E. coli) expression systems.
The evaluating of the results of different expression systems declared that none
of the mentioned systems can be considered to be generally superior to the other.
Meanwhile with considering the advantages and disadvantage of E. coli expression
system compared with other systems beside the molecular properties of Es, E. coli
expression system can be a preferred expression system for expressing of the Es
in large scale. Also, the molecular bioengineering and sustained release
formulations that lead to improving of its stability and bioactivity will be
discussed. Point mutation (P125A) of Es, addition of RGD moiety or an additional
zinc biding site to N-terminal of Es , fusing of Es to anti-HER2 IgG or heavy
chain of IgG, and finally loading of the endostar by PLGA and PEG- PLGA
nanoparticles and gold nano-shell particles are the effective bioengineering
methods to overcome to clinical changes of endostatin.
PMID- 28507937
TI - The Utilization of RNA Silencing Technology to Mitigate the Voriconazole
Resistance of Aspergillus Flavus; Lipofectamine-Based Delivery.
AB - Purpose: Introducing the effect of RNAi in fungi to downregulate essential genes
has made it a powerful tool to investigate gene function, with potential
strategies for novel disease treatments. Thus, this study is an endeavor to delve
into the silencing potentials of siRNA on cyp51A and MDR1 in voriconazole
resistant Aspergillus flavus as the target genes. Methods: In this study, we
designed three cyp51A-specific siRNAs and three MDR1-specific siRNAs and after
the co-transfection of siRNA into Aspergillus flavus, using lipofectamine, we
investigated the effect of different siRNA concentrations (5, 15, 25, 50nM) on
cyp51A and MDR1 expressions by qRT-PCR. Finally, the Minimum Inhibitory
Concentrations (MICs) of voriconazole for isolates were determined by broth
dilution method. Results: Cyp51A siRNA induced 9, 22, 33, 40-fold reductions in
cyp51A mRNA expres-sion in a voriconazole-resistant strain following the
treatment of the cells with concentrations of 5, 15, 25, 50nM siRNA,
respectively. Identically, the same procedure was applied to MDR1, even though it
induced 2, 3, 4, 10-fold reductions. The results demonstrated a MIC for
voriconazole in the untreated group (4ug per ml), when compared to the group
treated with cyp51A-specific siRNA and MDR1-specific siRNA, both at
concentrations of 25 and 50nM, yielding 2ug per ml and 1ug per ml when 25 nM was
applied and 2ug per ml and 0.5ug per ml when the concentration doubled to 50 nM.
Conclusion: In this study, we suggested that siRNA-mediated specific inhibition
of cyp51A and MDR1 genes play roles in voriconazole-resistant A.flavus strain and
these could be apt target genes for inactivation. The current study promises a
bright prospect for the treatment of invasive aspergillosis through the effective
deployment of RNAi and gene therapy.
PMID- 28507938
TI - Vitamin D3-Loaded Nanostructured Lipid Carriers as a Potential Approach for
Fortifying Food Beverages; in Vitro and in Vivo Evaluation.
AB - Purpose: Nanostructured lipid carriers (NLCs) composed of solid lipid and oil are
a new generation of lipid nanoparticles which have exhibited some merits over
traditional used lipid nanoparticles in fortifying food and beverages and
nutraceuticals delivery systems such as liposomes and solid lipid nanoparticles.
Methods: In this study, Precirol and Compritol as solid lipids, Miglyol and
Octyloctanoat as liquid lipids, Tween80, Tween20 and Poloxamer407 as surfactants
were used to prepare vitamin D3-loaded NLC dispersion using hot homogenization
method. The particle size and size distribution for all formulations were
evaluated by immediately after production and during a storage period of 60 days.
Results: The Precirol-based NLC showed superiority over Compritol-based NLC in
the point of physical stability. Results clearly suggested that an optimum
concentration of 3% of Poloxamer407 or 2% of Tween20 was sufficient to cover the
surface of nanoparticles effectively and prevent agglomeration during the
homogenization process. Octyloctanoat was introduced for the first time as a good
substituent for Miglyol in the preparation of NLC formulations. The vitamin D3
Intestinal absorption enhanced by the incorporating in NLCs. Conclusion: It was
concluded that NLC showed a promising approach for fortifying beverages by
lipophilic nutraceuticals such as vitamin D.
PMID- 28507939
TI - Variables Associated with Adherence to Stress Ulcer Prophylaxis in Patients
Admitted to the General Hospital Wards: A Prospective Study.
AB - Purpose: The dramatic increase in stress ulcer prophylaxis (SUP) prescribing
patterns over the past several years has raised concerns regarding to their
appropriate utilization. This prospective study attempted to evaluate the trend
of adherence to stress ulcer prophylaxis from admission until discharge in non-
Intensive care unit (ICU) setting. Additionally, we attempted to find those
variables associated with appropriate SUP administration. Methods: Data
collection was performed prospectively to evaluate 195 randomly selected adult
patients who received SUP or had indication for that in non-ICU wards of one of
the largest referral center in Iran, during 6 months. Adherence was studied
according to widely accepted American Society of Health system Pharmacists (ASHP)
guideline. Univariate and multivariate logistic regression was also performed to
detect associations related to misuse of SUP. Results: We recognized total
inappropriate use of SUP upon admission, during hospital stay and at discharge
were somewhat identical at different time points (61%, 80% and 77.4%
respectively). On the other hand, since small number of patients experienced SUP
underutilization, unfortunately this was not possible to elucidate factors that
may have effect on this flawed behavior. However, increasing age was identified
to be significant variable in SUP overutilization. Conclusion: This prospective
study highlighted inappropriate overutilization of SUP within non-critically ill
patients and found factors which predicted this behavior. Adherence during
hospital stay was also calculated for the first time in this study, which was
related to SUP adherence upon hospital admission.
PMID- 28507940
TI - Cord Blood Cells Responses to IL2, IL7 and IL15 Cytokines for mTOR Expression.
AB - Purpose: Mammalian target of rapamycin (mTOR)is important in hematopoiesis and
affect cell growth,differentiation and survival. Although previous studies were
identified the effect of cytokines on the mononuclear cells development however
the cytokines effect on mTOR in cord blood mononuclear cells was unclear. The aim
of this study was to evaluate mTOR expression in cord blood mononuclear and cord
blood stem cells (CD34+ cells) in culture conditions for lymphoid cell
development. Methods: Isolation of The mononuclear cells (MNCs) from umbilical
cord blood were done with use of Ficollpaque density gradient. We evaluated
cultured cord blood mononuclear and CD34+ cells in presece of IL2, IL7 and IL15
at distinct time points during 21 days by using flow cytometry. In this study, we
presented the role of IL2, IL7 and IL15 on the expression of mTOR in cord blood
cells. Results: mTOR expression were increased in peresence of IL2, IL7 and IL15
in day 14 and afterword reduced. However in persence of IL2 and IL15 expression
of mTOR significantly reduced. mTOR expression in CD34+ cells decreased
significantly from day7 to day 21 in culture. Conclusion: cytokines play
important role in mTOR expression during hematopoiesis and development of cord
blood mononuclear cells.
PMID- 28507941
TI - In vitro Cytotoxicity Effects of 197Au/PAMAMG4 and 198Au/PAMAMG4 Nanocomposites
Against MCF7 and 4T1 Breast Cancer Cell Lines.
AB - Purpose: Study on gold based therapeutic agents for cancer cells deracination has
become under scrutiny in recent years owing to effective treatments are not
available for rapidly progressive cancers. The aim of present study was to
examine efficiency of radioactive 198Au/PAMAMG4 and non-radioactive 197Au/PAMAMG4
nancomposites against 4T1 and MCF7 breast cancer cell lines. Methods: The PAMAMG4
dendrimer was treated with the gold anions and then, the mixture was chemically
reduced by NaBH4. Prepared 197Au/PAMAMG4 was bombarded by thermal neutrons in the
Tehran Research Reactor to 198Au/PAMAMG4 be produced. Prepared nanocomposites
were characterized by means of FT-IR, 1H NMR, Zeta-potential measurements, TEM
and EDX analyses. The radionuclidic purity of the 198Au/PAMAMG4 solution was
determined using purity germanium (HPGe) spectroscopy and its stability in the
presence of human serum was studied. In vitro studies were carried out to compare
toxicity of PAMAMG4, 197Au/PAMAMG4 and 198Au/PAMAMG4 towards 4T1 and MCF7
cancerous cells and C2C12 normal cell lines. Results: Characterization results
exhibited that invitro agents, 197Au/PAMAMG4 and 198Au/PAMAMG4, were synthesized
successfully. Cells viability after 24 h, 48 h, and 72 h incubation, using MTT
assay showed that the toxicity of 198Au/PAMAMG4 is significantly superior in
comparison with 197Au/PAMAMG4 and PAMAMG4. Furthermore, the toxicity of
198Au/PAMAMG4 was higher on cancerous cells especially in higher level of
concentrations after 72 hours (P<0.05). Conclusion: In the current study, the
preparation of 197Au/PAMAMG4 and 198Au/PAMAMG4 is described and the cytotoxic
properties of them against the MCF7, 4T1 cancerous cells and C2C12 normal cells
were evaluated using MTT assay.
PMID- 28507942
TI - Quality Properties of Sesame and Olive Oils Incorporated with Flaxseed Oil.
AB - Purpose: Suitable ratio of essential fatty acids has an important role in
maintaining good health. There is no pure oil with an ideal fatty acid
composition and oxidative stability. The main goal of the present study was to
evaluate the physical, chemical and nutritional properties of oil obtained by
blending flaxseed oil as a rich source of omega3 fatty acids with sesame and
olive oils. Methods: Three different ratios (65:30:5, 60:30:10 and 55:30:15) were
prepared using olive, sesame and flaxseed oils. These mixtures were stored at 4
degrees C and 24 degrees C and their quality and physicochemical properties were
determined by measuring the fatty acid composition, phenolic compound, peroxide,
anisidine values and schaal tests. Results: Fatty acid composition indicated that
adding 10% and 15% flaxseed oil into blends have suitable ratio of essential
fatty acids. The sample which contained 5% flaxseed oil had the highest phenolic
content among treatments and these compounds showed a significant decrease during
storage. A significant increase (p<0.05) was observed in peroxide values of all
samples during storage. Increasing the flaxseed oil content in the blends, lead
to an increase of the anisidine value. Conclusion: Blending sesame and olive oils
with flaxseed oil produced oil blends with a good balance of essential fatty
acids. Although peroxide and anisidine values increased during storage of the oil
blends; the blends were of a good quality for home and industrial use.
PMID- 28507943
TI - Effect of Solubilizers on the Androgenic Activity of Basella Alba L.
(Basellaceae) in Adult Male Rats.
AB - Purpose: Solubilizers play an important role in dissolution of pharmacological
ingredients and should properly dissolve the active principle(s) while preserving
its activities. This study investigated the effect of starch, gelatin,
methylcellulose and polyvinylpyrrolidone 10000 in the preservation of the
androgenic activity of the methanol extract Basella alba (MEBa). Methods:
Different groups of male albino rats were orally given the MEBa (1 mg/kg)
dissolved into either 1% gelatin (1% gel), %1 methylcellulose (1% MC) and 1%
polyvinylpyrrolidone 10000 (1% PVP 10000) or 2% starch solution (2% SS) for 30
days. Thereafter, animals were sacrificed and serum testosterone and creatinine
levels as well as alanine aminotransferase (ALT) activity determined. Vital and
reproductive organs were dissected out and weighed, while liver thiobarbituric
acid reactive substances (TBARS) and glutathione levels were determined. Results:
Different treatments did not affect the animal body and organ weights. The MEBa
stimulatory effect on testosterone production was preserved with 2% SS and 1% PVP
10000 as vehicles. Increased liver glutathione and TBARS levels were also
observed in the animals fed with the MEBa dissolved in 2% SS and 1% Gel,
respectively, while other biochemical parameters remained unchanged. Conclusion:
Starch and polyvinylpyrrolidone 10000 stand as good preservation agents for MEBa
androgenic activity, with starch exhibiting additional antioxidant activity
through increase of glutathione levels.
PMID- 28507944
TI - A Survey on Phytochemical Composition and Biological Activity of Zygophyllum
fabago from Iran.
AB - Purpose: Zygophyllum fabago L. (Z. fabago) is a widespread perennial herb which
is used as a medicinal plant in traditional medicine of Iran, Turkey and China.
The present study was a survey on phytochemical constituents and biological
activities of this plant. Methods: Methanolic extract of the roots was
fractionated over a C-18 pre-packed cartridge (Sep-pak) and chromatographic
separation was performed on a reversed-phase preparative HPLC. Structural
elucidation of the isolated compounds was carried out using UV, 1H-NMR and 13C
NMR spectral analyses. Furthermore, the chemical compositions of the essential
oil of the aerial parts were identified by GC-MS analysis. Antiproliferative and
antioxidant activities of all extracts from aerials were determined by MTT and
DPPH assays, respectively. Results: Phytochemical investigation on the plant
roots led to the isolation and identification of two the 60% methanol-water Sep
pak fraction, a prenylated flavone glycoside, 6-C-prenyl-7-O-[ beta -D-4'''-O
acetyl-glucopyranosyl-(1'''->2'')-beta-D-glucopyranosyl] apigenin, which was
named as a Zygocaperoside and also, other flavonoid, was named as the
Isorhamnetin -3-O glucoside. None of the extracts showed antiproliferative effect
against cancerous cells. However, among the extracts, methanolic extract
indicated antioxidant activity. Moreover, essential oils of flowers and leaves of
plant have high amounts of sesquiterpene hydrocarbons and diterpenoides.
Conclusion: The results of present study introduce Z. fabago roots as a new
source of flavonoid glycosides and suggest it as an appropriate candidate for
further pharmacological studies.
PMID- 28507945
TI - Antimicrobial Activity of Two Garlic Species (Allium Sativum and A. Tuberosum)
Against Staphylococci Infection. In Vivo Study in Rats.
AB - Purpose: This study observed the effect of garlic extracts and amoxicillin
against an induced staphylococcal infection model. MIC and MBC were also obtained
for aqueous extracts of Allium sativum (Asa) and Allium tuberosum (Atu) against
Staphylococcus aureus penicillin-sensitive (PSSA - ATCC 25923) and MRSA (ATCC
33592). Methods: Granulation tissues were induced in the back of 205 rats. After
14 days, 0.5 mL of 108 CFU/mL of PSSA or MRSA were injected inside tissues. After
24h, animals were divided: G1 (Control) - 0.5 mL of NaCl 0.9%; G2 - Asa 100 mg/kg
or 400mg/kg; G3 - Atu 100 mg/kg or 400 mg/kg; G4 - amoxicillin suspension 50
mg/kg, considering PSSA infection; and G5 (Control) - 0.5 mL of NaCl 0.9%; G6 -
Asa 400mg/kg; G7 - amoxicillin 50 mg/kg; and G8 - Asa 400 mg/kg + amoxicillin 50
mg/kg for MRSA. All treatments were administered P.O. every 6h. Animals were
killed at 0, 6, 12 and 24h. Samples were spread on salt-mannitol agar. Colonies
were counted after 18 h at 37 degrees C. Atu was not able to inhibit or kill
PSSA and MRSA. Considering Asa, MIC and MBC against PSSA were 2 mg/mL and 4
mg/mL, respectively; and 16 mg/mL and 64 mg/mL against MRSA. Results: No effect
was observed in vivo for control, Asa 100 mg/kg and Atu 100 mg/kg, while
amoxicillin, Atu 400 mg/kg and Asa 400 mg/kg decreased PSSA counts in all-time
points. No effect of any group against MRSA was observed at any time. Conclusion:
Thus, A. sativum and A. tuberosum were able to reduce PSSA infection, but not
MRSA infection.
PMID- 28507946
TI - Conditioned Medium of Wharton's Jelly Derived Stem Cells Can Enhance the
Cartilage Specific Genes Expression by Chondrocytes in Monolayer and Mass Culture
Systems.
AB - Purpose: Mesenchymal stem cells (MSCs) have been introduced for cell therapy
strategies in osteoarthritis (OA). Despite of their capacity for differentiation
into chondrocyte, there are some evidences about their life-threatening problem
after transplantation. So, some researchers shifted on the application of stem
cells conditioned medium. The goal of this study is to evaluate whether Wharton's
jelly derived stem cell conditioned medium (WJSCs-CM) can enhance the gene
expression profile by chondrocytes in monolayer and mass culture systems.
Methods: Conditioned medium was obtained from WJSCs at fourth passage. Isolated
chondrocytes were plated at density of 1*106 for both monolayer and high density
culture. Then cells in both groups were divided into control (received medium)
and experiment group treated with WJ-CM for 3 and 6 days. Samples were prepared
to evaluate gene expression profile of collagen II, aggrecan, cartilage
oligomeric matrix protein (COMP) and sox-9 using real-time RT-PCR. Results: After
3 days, Chondrocytes treated with WJSCs-CM expressed significantly higher level
of genes compared to the control group in both culture systems. After 6 days, the
expression of genes in monolayer cultivated chondrocytes was decreased but that
of the mass culture were up-regulated significantly. Conclusion: WJ-SCs-CM can
increase the expression of cartilage-specific genes and can be introduced as a
promoting factor for cartilage regeneration.
PMID- 28507947
TI - Preparation, Optimization and Activity Evaluation of PLGA/Streptokinase
Nanoparticles Using Electrospray.
AB - Purpose: PLGA nanoparticles (NPs) have been extensively investigated as carriers
of different drug molecules to enhance their therapeutic effects or preserve them
from the aqueous environment. Streptokinase (SK) is an important medicine for
thrombotic diseases. Methods: In this study, we used electrospray to encapsulate
SK in PLGA NPs and evaluate its activity. This is the first paper which
investigates activity of an electrosprayed enzyme. Effect of three input
parameters, namely, voltage, internal diameter of needle (nozzle) and
concentration ratio of polymer to protein on size and size distribution (SD) of
NPs was evaluated using artificial neural networks (ANNs). Optimizing the SD has
been rarely reported so far in electrospray. Results: From the results, to obtain
lowest size of nanoparticles, ratio of polymer/enzyme and needle internal
diameter (ID) should be low. Also, minimum SD was obtainable at high values of
voltage. The optimum preparation had mean (SD) size, encapsulation efficiency and
loading capacity of 37 (12) nm, 90% and 8.2%, respectively. Nearly, 20% of SK was
released in the first 30 minutes, followed by cumulative release of 41% during 72
h. Activity of the enzyme was also checked 30 min after preparation and 19.2%
activity was shown. Conclusion: Our study showed that electrospraying could be an
interesting approach to encapsulate proteins/enzymes in polymeric nanoparticles.
However, further works are required to assure maintaining the activity of the
enzyme/protein after electrospray.
PMID- 28507949
TI - Voltammetric Determination of Ivabradine Hydrochloride Using Multiwalled Carbon
Nanotubes Modified Electrode in Presence of Sodium Dodecyl Sulfate.
AB - Purpose: A new sensitive sensor was fabricated for the determination of
ivabradine hydrochloride (IH) based on modification with multiwalled carbon
nanotubes using sodium dodecyl sulfate as micellar medium to increase the
sensitivity. Methods: The electrochemical behavior of IH was studied in Britton
Robinson buffer (pH: 2.0-11.0) using cyclic and differential pulse voltammetry.
Results: The voltammetric response was linear over the range of 3.984 x 10-6
3.475 x 10-5 mol L-1. The limits of detection and quantification were found to be
5.160 x 10-7 and 1.720 x 10-6 mol L-1, respectively. Conclusion: This method is
suitable for determination of IH in tablets and plasma.
PMID- 28507950
TI - Preparation and Characterization of Pistacia khinjuk Gum Nanoparticles Using
Response Surface Method: Evaluation of Its Anti-Bacterial Performance and
Cytotoxicity.
AB - Purpose: This study aims to prepare a novel, natural nanoparticle (NP) as a drug
carrier, which also has inherent therapeutic effects. Methods: Pistacia khinjuk
gum NPs were prepared and Response surface methodology (RSM) was used for
statistical analysis of data and optimizing the size of NPs. Results: NPs were in
the range of 75.85-241.3 nm. The optimization study was carried out, and an
optimized size (70.86nm) was obtained using DMSO as a solvent. The volume of the
organic phase was 111.25ul, and the concentration of gum was 1% w/v. The cell
viability assay was performed on the pure gum and NPs toward beta-TC3, MCF7, and
HT29 cell lines. It was observed that NPs have higher cytotoxic activity in
comparison with pure gum, and that the IC50value was achieved at 1% of NPs in
beta-TC3 cells. The obtained NPs demonstrated antibacterial activity against two
bacterial strains (Pseudomonas aeruginosa and Staphylococcus aureus). Conclusion:
Altogether, according to the obtained results, these NPs with inherent
cytotoxicity and antibacterial activity are an attractive carrier for drug
delivery.
PMID- 28507948
TI - Characterizing the Hot Spots Involved in RON-MSPbeta Complex Formation Using In
Silico Alanine Scanning Mutagenesis and Molecular Dynamics Simulation.
AB - Purpose: Implication of protein-protein interactions (PPIs) in development of
many diseases such as cancer makes them attractive for therapeutic intervention
and rational drug design. RON (Recepteur d'Origine Nantais) tyrosine kinase
receptor has gained considerable attention as promising target in cancer therapy.
The activation of RON via its ligand, macrophage stimulation protein (MSP) is the
most common mechanism of activation for this receptor. The aim of the current
study was to perform in silico alanine scanning mutagenesis and to calculate
binding energy for prediction of hot spots in protein-protein interface between
RON and MSPbeta chain (MSPbeta). Methods: In this work the residues at the
interface of RON-MSPbeta complex were mutated to alanine and then molecular
dynamics simulation was used to calculate binding free energy. Results: The
results revealed that Gln193, Arg220, Glu287, Pro288, Glu289, and His424 residues
from RON and Arg521, His528, Ser565, Glu658, and Arg683 from MSPbeta may play
important roles in protein-protein interaction between RON and MSP. Conclusion:
Identification of these RON hot spots is important in designing anti-RON drugs
when the aim is to disrupt RON-MSP interaction. In the same way, the acquired
information regarding the critical amino acids of MSPbeta can be used in the
process of rational drug design for developing MSP antagonizing agents, the
development of novel MSP mimicking peptides where inhibition of RON activation is
required, and the design of experimental site directed mutagenesis studies.
PMID- 28507951
TI - The Phytochemical Bergenin Enhances T Helper 1 Responses and Anti-Mycobacterial
Immunity by Activating the MAP Kinase Pathway in Macrophages.
AB - Tuberculosis (TB) remains one of the greatest health concerns worldwide, which
has hindered socioeconomic development in certain parts of the world for many
centuries. Although current TB therapy, "Directly Observed Treatment Short
course," is effective, it is associated with unwanted side effects and the risk
for the generation of drug-resistant organisms. The majority of infected
individuals successfully confine the mycobacterial organisms and remain
asymptotic unless immune responses are perturbed. Thus, host immunity can protect
against TB and immunomodulation is therefore an attractive therapeutic option.
Previous studies have shown that TNF-alpha and Nitric Oxide (NO) in conjunction
with IFN-gamma-producing T helper 1 (Th1) cells play critical roles in host
protection against TB. Here, we show that bergenin, a phytochemical isolated from
tender leaves of Shorea robusta, activates the MAP kinase and ERK pathways and
induces TNF-alpha, NO and IL-12 production in infected macrophages. We further
show that bergenin induces Th1 immune responses and potently inhibits bacillary
growth in a murine model of Mycobacterium tuberculosis infection. These findings
identify bergenin as a potential adjunct to TB therapy.
PMID- 28507952
TI - Comparison of Growth and the Cytokines Induced by Pathogenic Yersinia
enterocolitica Bio-Serotypes 3/O: 3 and 2/O: 9.
AB - Pathogenic Yersinia enterocolitica is widely distributed in China where the
primary bio-serotypes are 3/O: 3 and 2/O: 9. Recently, the distribution of 2/O: 9
strains are being gradually replaced by 3/O: 3 strains where presently 3/O: 3
strains are the major pathogenic Y. enterocolitica in China. To identify the
growth conditions and cytokines induced by Y. enterocolitica and providing some
clues for this shift, we performed competitive growth in vitro and in vivo for
these two bio-serotype strains; and we also compared the cytokines induced by
them in infected BALB/C mice. We found 2/O: 9 strains grew more in vitro, while
3/O: 3 strains grew more in vivo regardless of using single cultures or mixed
cultures. The cytokines induced by the two strains were similar: interleukin-6
(IL-6), IL-9, IL-13, granulocyte colony-stimulating factor (G-CSF), chemokines
(KC), monocyte chemotactic protein 1 (MCP-1), macrophage inflammation protein
1alpha (MIP-1alpha), tumor necrosis factor-alpha (TNF-alpha), and RANTES were
statistically up-regulated upon activation of normal T cells compared to the
control. The cytokine values were higher in mixed infections than in single
infections except for IL-6, G-CSF, and KC. The data illustrated the different
growth of pathogenic Y. enterocolitica bio-serotype 3/O: 3 and 2/O: 9 in vitro
and in vivo, and the cytokine changes induced by the two strains in infected
BALB/C mice. The growth comparisons of two strains maybe reflect the higher
pathogenic ability or resistance to host immune response for Y. enterocolitica
bio-serotype 3/O: 3 and maybe it as one of the reason for bacteria shift.
PMID- 28507955
TI - Patient is centre of all Medical Research.
PMID- 28507953
TI - Influence of Microbes on Neutrophil Life and Death.
AB - Neutrophils are the most abundant leukocyte in humans and they are among the
first white cells recruited to infected tissues. These leukocytes are essential
for the innate immune response to bacteria and fungi. Inasmuch as neutrophils
produce or contain potent microbicides that can be toxic to the host, neutrophil
turnover and homeostasis is a highly regulated process that prevents unintended
host tissue damage. Indeed, constitutive neutrophil apoptosis and subsequent
removal of these cells by mononuclear phagocytes is a primary means by which
neutrophil homeostasis is maintained in healthy individuals. Processes that alter
normal neutrophil turnover and removal of effete cells can lead to host tissue
damage and disease. The interaction of neutrophils with microbes and molecules
produced by microbes often alters neutrophil turnover. The ability of microbes to
alter the fate of neutrophils is highly varied, can be microbe-specific, and
ranges from prolonging the neutrophil lifespan to causing rapid neutrophil lysis
after phagocytosis. Here we provide a brief overview of these processes and their
associated impact on innate host defense.
PMID- 28507956
TI - An Unusual Case of Giant Cell Tumor of First Metatarsal: A Rare Case Report and
Review of Literature.
AB - INTRODUCTION: Giant cell tumor (GCT) or osteoclastoma is an osteolytic, mostly
benign but locally aggressive tumor occurring in young adults at the epiphysis.
Area of predilection is mainly long bones (85-90%). 4% of GCT are also found in
iliac bone, spine and only 2% in hand (of which GCT phalanges are more common
than metacarpal). GCT of metatarsal is a very rare occurrence with very few cases
being reported so far. We report a case of GCT 1st metatarsal in a 40-year-old
male which is a very rare entity. We shall discuss the clinical features,
pathological and radiological hallmarks, and the various treatment modalities of
such lesion. CASE REPORT: A 40-year-old male presented with complain of swelling
over the dorsum of left foot for the duration of 2 years and pain in that foot
for 4 months. Swelling was insidious in onset and has progressively increased in
size. Pain was mild to moderate in intensity, dull aching and continuous. On
examination, there was a localized ovoid shaped swelling 7 by 4 cm over the
dorsum of the left foot opposing 1st and 2nd metatarsal area with well-defined
margins, tender on deep palpation, hard in consistency and the overlying skin was
free. Radiographs revealed an expansile osteolytic lesion of entire 1st
metatarsal involving the articular surface of tarsometatarsal joint and
metatarsophalangeal joint with impingement on 1st metatarsal and cortical
thinning. The classical "soap bubble appearance" was also present. Fine needle
aspiration cytology was done to confirm our diagnosis of GCT. According to
Campanacci et al., the tumor was histologically graded as Grade II tumor. A
reconstructive surgery with fusion of the Cuneiform metatarsa and
metatarsophalangeal joint was planned. The tumor was carefully removed with a
cuff of normal tissue and the proximal and distal joints were inspected. There
was no articular cartilage of the Cuneiform metatarsa joint. A fibular graft was
taken and was inserted into the troughs created in medial cuineform and proximal
phalanx and fixed with K-wire, both proximally and distally. The patient was
given a below knee cast for three months postoperatively. Full weight bearing was
started after 3 months. After 9 months of follow-up, the graft was well taken up
and there were no signs of recurrence both clinically and radiologically.
CONCLUSION: Local resection of the involved metatarsal with autograft or
allograft replacement is the preferred surgical treatment for several reasons.
First, no correlation has been found between the grade of GCT and the rate of
recurrence. Therefore, all giant tumors of foot should be considered locally
aggressive. In addition curettage with or without bone grafts has resulted in
recurrence rates of about 90%. Thus curettage is an unacceptable form of
treatment. Second, although amputation may prevent recurrence, it is cosmetically
deforming and decreases the function of the foot.
PMID- 28507954
TI - With Friends Like These: The Complex Role of Neutrophils in the Progression of
Severe Pneumonia.
AB - Pneumonia is a leading cause of death from infection in the United States and
across the globe. During pulmonary infection, clear resolution of host
inflammatory responses occurs in the absence of appreciable lung damage.
Neutrophils are the first wave of leukocytes to arrive in the lung upon
infection. After activation, neutrophils traffic from the vasculature via
transendothelial migration through the lung interstitium and into the alveolar
space. Successful pulmonary immunity requires neutrophil-mediated killing of
invading pathogens by phagocytosis and release of a myriad of antimicrobial
molecules, followed by resolution of inflammation, neutrophil apoptosis, and
clearing of dead or dying neutrophils by macrophages. In addition to their
antimicrobial role, it is becoming clear that neutrophils are also important
modulators of innate and adaptive immune responses, primarily through the release
of cytokines and recruitment of additional waves of neutrophils into the airways.
Though typically essential to combating severe pneumonia, neutrophil influx into
the airways is a double-edged sword: Overzealous neutrophil activation can cause
severe tissue damage as a result of the release of toxic agents including
proteases, cationic polypeptides, cytokines, and reactive oxygen species (ROS)
aimed at killing invading microbes. In extreme cases, the damage caused by
neutrophils and other innate immune mediators become the primary source of
morbidity and mortality. Here, we review the complex role of neutrophils during
severe pneumonia by highlighting specific molecules and processes that contribute
to pulmonary immunity, but can also drive progression of severe disease.
Depending on the identity of the infectious agent, enhancing or suppressing
neutrophil-mediated responses may be key to effectively treating severe and
typically lethal pneumonia.
PMID- 28507958
TI - Bifocal Cryptococcal Osteomyelitis in an Immunocompetent Male.
AB - INTRODUCTION: Cryptococcus neoformans commonly affects lungs and central nervous
system that to in immunocompromised individual. Bony involvement is extremely
rare and most common site is vertebrae and usual presentation is monofocal. CASE
REPORT: We present 18-year-old male with bifocal osteomyelitis of scapula and
tibia in immunocompetent male. CONCLUSION: Cryptococcal osteomyelitis should be
kept as a differential diagnosis in a patient as a primary diagnosis to avoid
diagnostic delay and morbidity associated with it.
PMID- 28507957
TI - Arthroscopic Synovectomy in Bilateral Lipoma Arborescens.
AB - INTRODUCTION: Lipoma arborescens (LA) is an uncommon condition that consists of a
villous lipomatous proliferation of the synovial membrane. Open synovectomy has
been previously selected as a curative treatment option. In recent years, some
authors have published good results with arthroscopic interventions. We describe
a well-documented case of bilateral LA of the knees treated with staged
arthroscopic synovectomy. CASE REPORT: A 48-year-old North American woman without
a history of trauma presented with recurrent effusions and mild pain in both knee
joints for many years. Magnetic resonance imaging examinations confirmed the
diagnosis of bilateral LA with multiple villous lipomatous synovial
proliferations pattern. Degenerative changes of the medial meniscus were detected
bilaterally. The patient underwent bilateral arthroscopic anterior synovectomy
and partial medial meniscectomy of the knee with three portal techniques.
Arthroscopic the knee joint contained a large number or finger-shaped synovial
proliferations with yellowish good vascularized diffuse villous masses in the
suprapatellar bursa and intercondylar fossa. The cartilage showed degenerative
changes with Outerbridge Grade II to III, which was particularly severe in the
femoropatellar compartment. Histopathological examination of the villous masses
demonstrated papillary hypertrophy, slight hyperplasia, vascular hyperplasia with
a slight degree of stromal fibrosis, and interstitial lymphoplasmacytic
inflammation. The adipose cells were reduced in number in relation to a normal
finding but had a normal aspect without any pathological changes. 25 months after
the first operation, the patient reported pain relief with the preserved
function. Magnetic resonance examination of both knee joints at the last follow
up showed no relapse of the disease. The Knee injury and Osteoarthritis Outcome
Score improved on the right knee joint from 39.3 preoperatively to 85.1 at the
last follow-up, and on the left knee joint from 54.2 preoperatively to 86.3 at
the last follow-up. CONCLUSION: Arthroscopic anterior synovectomy is an efficient
method of achieving good results in LA with multiple villous lipomatous synovial
proliferations pattern.
PMID- 28507959
TI - Intramuscular Arteriovenous Hemangioma of Thigh: A Case Report and Review of
Literature.
AB - INTRODUCTION: Skeletal muscle hemangiomas are uncommon soft tissue tumors; more
than 90% are misdiagnosed initially. They present as chronic pain and swelling in
a muscle with or without a history of trauma. Magnetic resonance imaging is the
investigation of choice. Many treatment modalities for the symptomatic
hemangiomas are available of which surgical excision is the most preferred. CASE
REPORT: We present an unusual case of pain, swelling, and restriction of
movements in the right knee following an episode of trauma in an 8-year-old boy
diagnosed to have intramuscular arteriovenous hemangioma in the vastusmedialis
and vastusintermedius for which he was treated by surgical excision and followed
for 2 years and found to have no recurrence. CONCLUSION: Skeletal muscle
hemangiomas are completely treatable; the knowledge of their natural history,
clinical findings, and imaging appearances are of great importance for proper
diagnosis and treatment.
PMID- 28507960
TI - A Case Report of Sleeve Fracture of the Patella in a Shield.
AB - INTRODUCTION: Sleeve fractures of the patella are rare fractures that only occur
in children. The diagnosis is difficult both clinically and radiologically since
the distal bony fragment may be too small to be detectable by radiography. A high
riding patella and hemarthrosis are important signs of sleeve fractures. CASE
REPORT: A 12-year-old boy was admitted to the emergency room after having felt a
severe pain in his left knee on kicking the ground while skateboarding earlier
that day. Knee swelling, tense hemarthrosis, and periarticular tenderness were
noted. On physical examination, an extension lag of 15 was observed. The active
range of motion of the injured knee was 45-90 degrees of flexion. Radiography
showed an avulsion fracture of the lower pole of the patella and a high-riding
patella. At the next day after the injury, we performed open reduction and
internal fixation surgery. Open reduction with transosseous tunneling and
cerclage wiring was performed because the distal bony fragment was too small for
tension band wiring to be used. At 9 months after surgery, there was no extension
lag, and the active range of motion of the injured knee was 0-140 degrees of
flexion. Callus formation over the fracture site and bone union was confirmed,
and the cerclage wire was removed. To date, he had no further symptoms and has
been able to carry out all types of physical activities, including skateboarding.
CONCLUSION: Although sleeve fractures in children are uncommon, it should be
considered a possibility in children with a chief complaint of pain around the
knee. Open reduction and internal fixation was effective in the treatment of
sleeve fracture of the patella.
PMID- 28507961
TI - Total Hip Arthroplasty Indicated for a Tuberculous Coxitis Complicating a
Controlled Acquired Imunodefficiency Syndrom Condition: A Preliminary Report
Concerning a Case.
AB - INTRODUCTION: Total hip arthroplasty (THA) remains controversial in active
tuberculosis (TB) infection because of the risks of septic loosening and
reactivation of the infection. We present a rare case of THA in a patient
positive for the human immunodeficiency virus (HIV) with active tuberculous
coxitis. The aim of this work is to share our experience and our preliminary
results. CASE REPORT: The patient was a 53-year-old Black African woman, positive
for the HIV, who was operated for implantation of a THA via the Hardinge approach
indicated for a severe painful hip with restriction of joint movement and limp. A
creamy-white liquid was noticed in the hip joint which was negative for urgent
Gram-staining. The surgery was completed with the implantation of a hybrid THA.
The post-operative period was uneventful, and she was put on antituberculous
drugs following a positive histology result for TB, and to continue her
antiretroviral drugs. She still has a satisfactory result for 3 years since her
surgery. CONCLUSION: On condition that the patient is put simultaneously on
triple antibiotics and antituberculous drugs, we propose that THA could be an
option in patient presenting with the association of HIV infection and active
tuberculous coxitis.
PMID- 28507962
TI - Dislocation Intermediate Cuneiform with Fracture Medial Cuneiform.
AB - INTRODUCTION: Dislocation of intermediate cuneiform is a rare injury in English
language literature. Dislocation of intermediate cuneiform with undisplaced
medial cuneiform fracture has been reported only once. We report the first case
of dislocation intermediate cuneiform with displaced medial cuneiform fracture.
CASE REPORT: A 43-year-old male was diagnosed of dislocation of intermediate
cuneiform with fracture medial cuneiform after a road traffic accident. This was
treated by a method of distractor application that is only reported in navicular
fracture dislocation. This treatment method avoids open reduction with minimal of
complications and good outcome. CONCLUSION: Distractor technique was applied for
the first time in cuneiform fracture dislocation in this case, and we recommend
it to avoid open reduction. The previous reported injuries in this region were
mostly treated by open reduction. Due to the rarity of this injury and technique,
our case adds to the literature a novel reduction method.
PMID- 28507963
TI - Evaluation of Efficacy of Three-dimensional Stainless Steel Mini-Plates in the
Treatment of Fractures of the Mandible: A Prospective Study.
AB - INTRODUCTION: The purpose of the study was to analyze whether adequate fracture
fixation can be achieved by three-dimensional (3D) stainless steel mini-plates
its ease of placement, whether the patient can resume function early and to find
out the need to do intermaxillary fixation. MATERIALS AND METHODS: In the
prospective study, we treated 12 patients and 17 fractured sites using 3D mini
plates. Once fracture reduction was achieved temporary intermaxillary fixation
(IMF) was done occlusion was achieved and the fractured segments were fixed using
3D plates either 4-holed or 6-holed of 2.5 mm thickness and 6-8 mm length screws.
IMF was removed subsequently. CONCLUSION: In none of the cases non-union or
malocclusion was noted. Similarly except for 2 cases which had associated
subcondylar fractures IMF was not done postoperatively. The patients were able to
achieve function immediately with a reasonable level of success. The interincisal
opening ranged from 18 to 23 mm in the first week to 40-56 mm after 1 month.
PMID- 28507964
TI - Intra-articular Migration of Broken Patellar Tension Band Wire: A Rare Case.
AB - INTRODUCTION: Comminuted fracture of patella is most commonly treated by tension
band wiring with cerclage wiring. Broken cerclage wiring after such surgery is
not uncommon but intra-articular migration of broken cerclage wire is rarely
known and described complication. CASE REPORT: A 51-year-old male patient of
Indian origin which was treated, 15 months back for fracture patella with tension
band wiring with cerclage wiring, presented with painful restriction of knee
movements for the last 4 weeks. X-ray showed cerclage wire had broken at multiple
sites with one broken piece migrated intra-articular. This case is unique due to
the size of migrated broken cerclage wire which was about 4.5 cm long, second the
anterior part of broken wire was hooked around anterior cruciate ligament, which
prevented its further migration otherwise neurovascular structures could have
been damaged. This intra-articular piece of wire was removed arthroscopically.
CONCLUSIONS: We recommend that all patients receiving bone fixation with wires
should be counseled about the risks of hardware failure and possible migration,
with the option of elective hardware removal discussed. In addition, when wire
breakage is detected radiologically, the patient should be strongly advised to
have the wires removed as soon as possible.
PMID- 28507965
TI - Posterior Hip Dislocation with Ipsilateral Femoral Head and Shaft Fracture -
Using a Temporary External Fixator as a Method for Closed Reduction.
AB - INTRODUCTION: Complex fractures are increasing because of various traumatic
mechanisms. They drift from standard classifications, and their treatment is
controversial. Of such cases are hip dislocations with associated fractures of
the ipsilateral femur. CASE REPORT: This case report describes the condition of a
30-year-old man involved in a motor vehicle collision. Clinical examination, X
rays, and computed tomography scan revealed a posterior hip dislocation with an
ipsilateral femoral head and mid-shaft fractures. The patient was treated by
closed reduction of hip dislocation using a temporarily applied external fixator
followed by intramedullary nailing of the femoral shaft. Achieving a closed
reduction is a challenge with ipsilateral fractures but it should be favored over
open reduction due to a lower risk of complications. The type of femoral head
fracture, in this case, may have aided in an easier reduction. CONCLUSION: Hip
dislocation is an orthopedic emergency and its treatment is challenging if
associated with ipsilateral fractures. The decision of a closed versus an open
approach should be made after considering the management plans of other injuries.
PMID- 28507966
TI - Ipsilateral Hip and Knee Dislocation with Open Tibial Fracture: A Case Report of
a Limb Threatening Injury.
AB - INTRODUCTION: Hip or knee dislocations are usually treated as a surgical
emergency, but ipsilateral hip and knee dislocation should be considered a dual
emergency that must be addressed immediately and reduced at the earliest. We
present here the sequence of events and the final functional outcome of one such
rare injury manages by us. CASE REPORT: A 22-year-old male was involved in a road
traffic accident. He presented to the emergency department in 4 h injury time
with painful deformities of the right hip and knee, along with Type I open wound
right leg with abnormal mobility suggestive of fracture in the ipsilateral leg.
CONCLUSION: Simultaneous ipsilateral hip and knee fracture-dislocation with open
tibial fracture is a rare injury that should be approached as limb-threatening
injury and dual orthopedic emergency. We report this case for its rarity and to
document that good results can be achieved with early appropriate treatment.
PMID- 28507967
TI - Surgery of a Rare Case of Multiple Synovial Osteochondromatosis of the Hip Joint.
AB - INTRODUCTION: Primary synovial osteochondromatosis of the hip is a benign
disorder, which is not frequently seen clinically. The characteristic of this
disease is proliferation of synovium and formation of loose bodies inside the
joint. It is known that only the loose bodies derived from synovium were called
synovial osteochondromatosis. Although it can take place in any joint, the knee
is most commonly affected, involvement of the hip joint is relatively rare. We
report a young man who has multiple synovial osteochondromatosis in his left hip.
CASE REPORT: A 21-year-old young man, who had progressive pain and functional
impairment of his left hip, came to our hospital. He complained that 2 years ago,
he began to feel painful of his left hip joint when walking and squatting.
Physical examination found that the motion range of the hip was obviously
limited, with internal rotation, abduction in particular. The Harris hip score
was just 38 points. X-ray shew multiple osteochondromatosis with mild
degenerative osteoarthritis existing inside the hip joint. Magnetic resonance
imaging shew that the synovial osteochondromatosis intersperse inside the hip
joint. During the operation, posterolateral incision of the hip was chosen with
dislocation of the femoral head for total exposure of the hip joint to debride
extensive loose bodies and proliferative synovial tissue. Pulse irrigation was
applied to flush out the residuals. More than 872 of osteochondromatosis were
removed out of the hip joint (some small ones were sucked during the operation).
The size of the loose bodies ranged from 3 cm * 3 cm * 2.5 cm to 0.2 cm * 0.2 cm
* 0.15 cm. Post-operation radiography shew most pathological tissues were taken
out. After the operation, the patient rehabilitated fast. The pain relieved and
he could bear weight and walked 3 days postoperatively. 1 and 3 months
postoperatively, the patient came to us for visit, and he said that he just had a
relatively satisfactory function of his affected hip. He could walk, slowly run,
and squat freely. But sometimes he could feel a bit painful on his left hip joint
after long walking and fatigue. And sometimes he could feel and hear mild
crepitus on the left hip joint. 12 months later, the patient came again and
complained that the pain of his operated hip became a bit more serious than
before since about 20 days ago. The range (internal rotation, abduction in
particular) of this hip joint could not live up to normal, compared with the
uninvolved hip in physical examination. X-ray shew osteoarthritis had become a
bit severer. The patient accepted the suggestion of prospective total hip
replacement. CONCLUSION: Multiple synovial osteochondromatosis is not a very
uncommon condition. However, there may be unusual presentations. It can take
place in any joint, the knee is most commonly affected, however, involvement of
the hip joint is relatively rare as was seen in our patient.
PMID- 28507968
TI - Posttraumatic Static Volar Intercalated Segment Instability - Iatrogenic or
Missed Injury.
AB - INTRODUCTION: Carpal instability is broad category consisting of various patterns
of injury, with dissociative type more common. CASE REPORT: A 13 -year -old boy
presented at 6 months following a fall with restriction of wrist movements.
Patient had sustained a closed distal one -third both bones fracture forearm
fixed with K -wire, and volar lunate instability was found during sequential
follow -up. CONCLUSION: Posttraumatic carpal instability should be identified at
the earliest to avoid poor hand function and morbidity associated with it.
PMID- 28507969
TI - Core Decompression with Synthetic Grafting as a Joint Preservation Strategy in
Humeral Avascular Necrosis Due to Sickle Cell Anemia: A Case Report.
AB - INTRODUCTION: Avascular necrosis (AVN) of the femoral or humeral heads in
patients with sickle cell anemia is a common and painful condition. There is
currently no gold standard treatment protocol for this condition. Typically, the
pain is managed with narcotics and activity restriction until there has been
collapse of the subchondral bone with a degree of arthrosis sufficient to warrant
total joint arthroplasty. This method entails prolonged pain for the patient and
decreases the ability to function occupationally and recreationally. CASE REPORT:
A 51-year-old African-American woman with a history of sickle cell anemia
presented for the evaluation of significant bilateral shoulder pain that was
confirmed to be AVN via radiographs and magnetic resonance imaging of both her
humeral heads without joint collapse. She tried and failed conservative
management with physical therapy and optimization of sickle cell treatment with
pain medications for years, so she desired surgical management. Arthroscopically
assisted core decompression of her humeral heads with synthetic grafting was
performed in an attempt at joint preservation. CONCLUSION: This report
demonstrates a technique of staged decompression of necrotic bone in the
bilateral humeral heads with synthetic bone grafting to determine if this could
function as a joint preservation strategy. This procedure was considered
successful to alleviate the patients' pain in both of her arms. The application
of this procedure is significant because it could be used in various future
medical joint preservation cases for a wide range of patients.
PMID- 28507970
TI - A New Technique for Surgical Treatment of Proximal Hamstring Tendinopathy in a
Triathlon Athlete.
AB - INTRODUCTION: Proximal hamstring tendinopathy (PHT) is the result of chronic
overload caused by repetitive eccentric contraction. Surgical treatment becomes
an option for patients with chronic symptoms that do not respond to conservative
treatment. CASE REPORT: This report describes a case of a 48-year-old man, an
amateur triathlete, with deep gluteal pain in the left hip for 12 months, leading
to a decline in sports performance. Magnetic resonance imaging revealed
abnormalities that suggested a PHT. Surgery was indicated following the failure
of conservative treatments. Debridement of the conjoint tendon and its
reinsertion associated with semimembranosus tenotomy showed good results and is
thus an option for the treatment of this pathology after 12 months of follow-up.
CONCLUSION: This article provides surgeons with a new surgical option for this
debilitating condition with clinical and functional improvement after 12 months
of follow-up.
PMID- 28507971
TI - Lethal Necrotizing Fasciitis Triggered by Plaster: Case Report and Review of
Literature.
AB - INTRODUCTION: Plasters have been frequently associated with known complications
such as infection, and compartment syndrome or deep vein thrombosis. However,
life-threatening complication of necrotizing fasciitis (NF) has not been
frequently attributed to plaster. CASE REPORT: We had a case of a 62-year male
developing a lethal NF triggered by a below knee plaster for undisplaced fracture
medial malleolus after twisting injury. He had no history suggestive of diabetes,
renal impairment, and predisposing allergic factors or any comorbidity. Despite
early diagnosis and aggressive management with above knee amputation, death
occurs due to septic shock on the 20th day. A similar case of reported lethal NF
triggered by plaster has also been reviewed in this report. CONCLUSION: This case
highlights a life-threatening rare complication of plaster and author recommends
thorough clinical history taking, precleaning of limb, use of sterile water and
use of adequate wrap around skin for gypsum plasters as prevention apart from
high index of suspicion for early diagnosis, and rapid management.
PMID- 28507972
TI - Bilateral Coracoid Avulsion Fractures with Unilateral Anterior Instability with
Glenoid Bone Loss: Use of Avulsed Fragment for Reconstruction of Glenoid.
AB - INTRODUCTION: Coracoid fractures are often missed since the fracture is not
visualized in a routine anteroposterior view of the shoulder and special views
are not ordered. Shoulder dislocation is common but it is rare to have a
dislocation with a coracoid fracture. The purpose of this paper is to present the
rare occurrence of bilateral coracoid fractures in a patient with unilateral
anterior shoulder instability managed using the same fractured coracoid fragment
by the latarjet procedure. CASE REPORT: We report a case of 48 -year -old male
who presented to us with a history of recurrent dislocations of the left
shoulder. He had frequent episodes of tonic-clonic seizures 5 years back. He was
diagnosed to be suffering from neurocysticercosis of the brain for which he was
successfully treated. He did not have any episode of seizure later, but he
continued to have repeated episodes of dislocation on his left side only. On
examination of his left shoulder, he had normal range of motion. He was found to
be very apprehensive, even in the midrange. This made us to suspect glenoid bone
loss and hence both magnetic resonance imaging and three -dimensional computed
tomography (CT) scan of the left shoulder were ordered. The CT scan revealed
bilateral coracoid fractures along with glenoid bone loss. An open bony procedure
including iliac crest bone graft was planned after a diagnostic arthroscopy
keeping in mind that the latarjet procedure may not be possible due to the
coracoid fracture. During the operation, we found that the coracoid fragment was
large enough to perform a latarjet procedure rather than doing an iliac crest
bone graft. This itself provided stability of the shoulder on abduction and
external rotation by providing a bony block not requiring any further procedure
for the Hill -Sachs lesion. CONCLUSION: Epileptic patients should undergo CT scan
evaluation for glenoid bone loss, large Hill -Sachs lesion and to rule out
coracoid fractures to plan for bony stabilization procedure and since we have
used the same fractured coracoids fragment for latarjet procedure and found to be
successful, this add on the knowledge to the orthopedic community.
PMID- 28507973
TI - Intratendinous Ganglion Cyst of the Semitendinosus Tendon: First Reported Case
and Literature Review.
AB - INTRODUCTION: Ganglion cysts are commonly seen in wrist joints and knee joint,
but intra-tendinous ganglion cysts are extremely rare. We report the first case
of intratendinous ganglion cyst of semi-tendinous tendon. CASE REPORT: A 4-year
old boy presented with painless soft tissue swelling over knee with no history of
recent trauma. Radiograph was normal and USG showed a well-defined hypoechoic
cystic lesion. Patient was taken for surgery and the lesion was removed. Lesion
came out to be a ganglion cyst originating from the semitendinosus tendon. Post
operative USG was done to confirm complete removal of the ganglion. CONCLUSION:
Intra-articular ganglion cysts are common, and we find it regularly in our daily
practice. However, we should be aware of the occurrence of intratendinous
ganglion cysts also which on examination may look like a lipoma. Thus for all
cysts around the tendons, an USG is must. Also repeat USG should be done to rule
out incomplete excision and recurrence.
PMID- 28507974
TI - A Rare Presentation of Cervical Spine Osteochondroma.
AB - INTRODUCTION: Cervical spine osteochondromas are rare tumors that usually involve
the posterior spinal elements. Osteochondromas of the cervical spine presenting
anteriorly as a mass over the supraclavicular region has not been reported in the
literature. CASE REPORT: A 12-year-old boy presented with right sided
supraclavicular swelling. Plain radiographs revealed a bony mass. Computerized
tomography (CT) and magnetic resonance imaging scans of the cervical region
showed a bony mass arising from pedicle and encroaching onto lamina of C6
vertebra. He underwent excision biopsy of the mass through an anterior approach.
The histopathological diagnosis was osteochondroma. At 4-year follow-up, he was
asymptomatic and CT scan revealed no recurrence. CONCLUSION: Tumors arising from
the posterior elements are difficult to diagnose by plain radiographs alone and
require special imaging modalities to show their exact location, nature, and
extent.
PMID- 28507975
TI - Charcot Fracture in the Calcaneus after Total Knee Arthroplasty: A Case Report.
AB - INTRODUCTION: Only a few reports have described calcaneus fractures after total
knee arthroplasty (TKA). Therefore, in this report, we describe a case of
calcaneal avulsion fracture that occurred 5 weeks after a TKA in a relatively
young male patient with syphilis. CASE REPORT: A 63-year-old man with syphilis
had Charcot joint of the right knee. The patient developed severe varus deformity
and contracture and experienced severe pain in the knee. TKA was performed to
alleviate the pain and improve the patient's gait. The patient noticed slight
heel pain 4 weeks after the TKA, and a calcaneus avulsion fracture in the
ipsilateral foot was diagnosed without any trauma 1 week later. Open reduction
internal fixation was performed with cannulated cancellous screws and a cerclage
wire. 3 weeks after the surgery, partial weight bearing was permitted in an
orthotic device. Full weight-bearing was allowed at 7 weeks after surgery. The
surgical wounds healed without complications. The calcaneus fracture successfully
achieved bone union with appropriate surgical intervention and aftercare.
CONCLUSION: The previous studies have shown that calcaneus stress fracture may
occur in elderly osteoporotic women after TKA. Patients with peripheral
neuropathy may develop a Charcot fracture after minimal trauma because of
decreased protective sensation, even if the patient is a relatively young man
without osteoporosis. Charcot joint disease is also considered to be a risk
factor for calcaneal stress fracture and Charcot fracture after TKA.
PMID- 28507976
TI - Painful Pseudowinging and Snapping of Scapula due to Subscapular Osteochondroma:
A Case Report.
AB - INTRODUCTION: Osteochondroma or exostosis is most common benign bone tumors. They
are usually seen in the metaphyses of long bones with more than 35% of cases
affecting the bone around the knee and are seldom found in flat bones like
scapula. When present in scapula, they may cause abnormal scapulothoracic
movements leading to pain, snapping, and pseudowinging of scapula. CASE REPORT:
We describe a novel case of osteochondroma arising on the ventral aspect of right
scapula in a 16-year-old otherwise healthy female patient causing snapping and
pseudowinging of scapula and occasional pain in affected area. X-ray and computed
tomography findings were consistent with an abnormal bony mass arising on ventral
aspect of superior border of the scapula. The patient was treated with open
extraperiosteal resection of the mass with relief of symptoms. The
histopathological diagnosis was consistent with osteochondroma with no signs of
malignancy. CONCLUSION: In a patient with winging and snapping of scapula one
should be aware of rare diagnosis osteochondroma along with other more common
etiology.
PMID- 28507977
TI - A Sub-acute Septic Arthritis of the Knee; a Sequelae to Thorn Prick Injury of
Patella: A Case Report.
AB - INTRODUCTION: Sub-acute septic arthritis of knee following a thorn prick injury
to patella is an uncommon condition and seen in active playful children. The
child may be afraid to narrate the incident to their parents or examining doctor,
so a high index of suspicion is must. The delayed presentation is inevitable.
Early synovitis due to the organic biological foreign body may progress to septic
arthritis, if untreated may result in knee stiffness or chronic osteomyelitis of
patella. CASE REPORT: We report a case of thorn prick injury to the left patella
in an 8-years-old boy who neglected the incident of thorn prick while playing
with his peer group 10 days ago and presented with features of sub-acute septic
arthritis. He was treated by arthrotomy, double inspection of the patella,
removal of foreign body, synovectomy, lavage, antibiotics, and aggressive
rehabilitation with an excellent outcome. CONCLUSION: Sub-acute synovitis in
active playful children should raise the suspicion of thorn prick even though no
proper history is explained. Organic foreign body from plant materials is
radiolucent and easily missed. High suspicion and timely surgical intervention,
double inspection during arthrotomy identifies the foreign body. Once removed,
with proper antibiotic and physiotherapy protocol followed has an excellent
outcome.
PMID- 28507978
TI - Modified Tension - Slide Technique for Anatomical Distal Biceps Tenodesis using a
Bicortical EndoButton and a Tenodesis Screw.
AB - INTRODUCTION: Many surgical techniques have been described in the literature. In
this article, we describe surgical technical details along with tips and tricks
of distal biceps tendon tenodesis using the EndoButton and tension - slide
technique, a modification of the suspensory cortical button technique, which
allows the surgeon to tension and repairs the biceps tendon through the single
longitudinal anterior incision. This modification in surgical technique of using
dual implants, i.e., EndoButton and interference screw as fixation tools and
concept of tendon sliding principle made this procedure unique. In this article,
we describe surgical technique along with tips and tricks of distal biceps tendon
tenodesis using the EndoButton and tension - slide technique and also discussed
about modification of EndoButton technique reported in many other articles to
overcome the possible complications. CASE REPORT: We report six consecutive
patients, presented with distal biceps tendon rupture (4 acute; 2 chronic cases)
between June 2013 and March 2015, who underwent single-incision, anatomical
distal biceps tenodesis procedure with bicortical EndoButton and tenodesis screw
using tension slide technique. Radiographs were taken immediate post-operative to
document for displacement or loosening of EndoButton if any. CONCLUSION: The use
of an EndoButton and an interference screw for repairing distal biceps tendons
have been previously described. We describe a modification of originally
described technique which is worth considering, as it provides two levels of
fixation, whilst avoiding possible complications of such procedures. It is ideal
for repairing both acute and chronic ruptures, without the need for allograft or
autograft augmentation and describes detailed technical steps to avoid possible
iatrogenic complications.
PMID- 28507979
TI - Microtubule-associated protein tau is associated with the resistance to docetaxel
in prostate cancer cell lines.
AB - Tau, a microtubule-associated protein, has been investigated primarily in
neurons. Recently, tau has been explored to be associated with increased drug
resistance in various kinds of cancers. We found that the tau was expressed in
prostate cancer cell lines DU145 and PC-3. We also reported that recurrent
prostate cancer cells after docetaxel treatment have higher levels of microtubule
associated protein tau. In vitro, inactivation of tau by gene knockdown
suppressed cell proliferation and sensitized docetaxel cytotoxicity. Also, our
results demonstrated that the PI3K/Akt/mTOR pathway was upregulated in DU145
docetaxel-resistant cells compared with the DU145-naive cells. Thus, targeting
tau protein and PI3K/Akt/mTOR pathway are promising strategies to enhance
docetaxel response for the treatment of prostate cancer.
PMID- 28507980
TI - Hypertension in the Pediatric Kidney Transplant Recipient.
AB - Hypertension after kidney transplant is a frequent occurrence in pediatric
patients. It is a risk factor for graft loss and contributes to the significant
burden of cardiovascular disease (CVD) in this population. The etiology of
posttransplant hypertension is multifactorial including donor factors, recipient
factors, medications, and lifestyle factors similar to those prevalent in the
general population. Ambulatory blood pressure monitoring has emerged as the most
reliable method for measuring hypertension in pediatric transplant recipients,
and many consider it to be essential in the care of these patients. Recent
technological advances including measurement of carotid intima-media thickness,
pulse wave velocity, and myocardial strain using specked echocardiography and
cardiac magnetic resonance imaging have improved our ability to assess CVD
burden. Since hypertension remains underrecognized and inadequately treated, an
early diagnosis and an appropriate control should be the focus of therapy to help
improve patient and graft survival.
PMID- 28507981
TI - A Quasi-Experimental Study of a Movement and Preliteracy Program for 3- and 4
Year-Old Children.
AB - OBJECTIVE: Approximately 28% of children are not ready for kindergarten, 91% are
inactive according to current guidelines, and 21% are overweight/obese. Early
intervention to strengthen movement and preliteracy skills may help to curb the
concerning rates of poor school readiness, inactivity, obesity, and subsequently
positively impact health across the lifespan. The objective of this pilot study
was to evaluate the effectiveness of a motor and preliteracy skill program for a
community sample of 3- to 4-year-old children. METHODS: A quasi-experimental
study design was used. The program was run for 1 h/week for 10 weeks and
consisted of movement skill instruction, free play, and an interactive reading
circle with care-giver involvement throughout each session. Movement and
preliteracy skills were assessed in all children pre- and post-intervention using
the Peabody Developmental Motor Scales-2nd edition, the Preschool Word and Print
Awareness tool, and the Phonological Awareness Literacy Screening tool. RESULTS:
Nineteen families (experimental group, n = 8; control group, n = 11) were
recruited (mean age = 3 years, 8 m; 47% male). There was a significant effect of
group on gross motor raw scores overall [F(1, 16) = 4.67, p < 0.05; [Formula: see
text]] and print-concept knowledge [F(1, 16) = 11.9, p < 0.05; [Formula: see
text]]. CONCLUSION: This study was one of the first to examine the impact of a
community-based movement skill and preliteracy program with care-giver
involvement in preschool children. Future research should continue to explore the
effects of the program with larger and more diverse samples on multiple health
and developmental outcomes. CLINICAL TRIAL REGISTRATION: Play and Preliteracy
among Young Children (PLAY) NCT02432443.
PMID- 28507982
TI - The Role of Carrageenan and Carboxymethylcellulose in the Development of
Intestinal Inflammation.
AB - Although the exact pathophysiology remains unknown, the development of
inflammatory bowel disease (IBD) is influenced by the interplay between genetics,
the immune system, and environmental factors such as diet. The commonly used food
additives, carrageenan and carboxymethylcellulose (CMC), are used to develop
intestinal inflammation in animal models. These food additives are excluded from
current dietary approaches to induce disease remission in Crohn's disease such as
exclusive enteral nutrition (EEN) using a polymeric formula. By reviewing the
existing scientific literature, this review aims to discuss the role that
carrageenan and CMC may play in the development of IBD. Animal studies
consistently report that carrageenan and CMC induce histopathological features
that are typical of IBD while altering the microbiome, disrupting the intestinal
epithelial barrier, inhibiting proteins that provide protection against
microorganisms, and stimulating the elaboration of pro-inflammatory cytokines.
Similar trials directly assessing the influence of carrageenan and CMC in humans
are of course unethical to conduct, but recent studies of human epithelial cells
and the human microbiome support the findings from animal studies. Carrageenan
and CMC may trigger or magnify an inflammatory response in the human intestine
but are unlikely to be identified as the sole environmental factor involved in
the development of IBD or in disease recurrence after treatment. However, the
widespread use of carrageenan and CMC in foods consumed by the pediatric
population in a "Western" diet is on the rise alongside a corresponding increase
in IBD incidence, and questions are being raised about the safety of frequent
usage of these food additives. Therefore, further research is warranted to
elucidate the role of carrageenan and CMC in intestinal inflammation, which may
help identify novel nutritional strategies that hinder the development of the
disease or prevent disease relapse post-EEN treatment.
PMID- 28507983
TI - Epinephrine Use during Newborn Resuscitation.
AB - Epinephrine use in the delivery room for resuscitation of the newborn is
associated with significant morbidity and mortality. Evidence for optimal dose,
timing, and route of administration of epinephrine during neonatal resuscitation
comes largely from extrapolated adult or animal literature. In this review, we
provide the current recommendations for use of epinephrine during neonatal
resuscitation and also the evidence behind these recommendations. In addition, we
review the current proposed mechanism of action of epinephrine during neonatal
resuscitation, review its adverse effects, and identify gaps in knowledge
requiring urgent research.
PMID- 28507985
TI - Control of Neuronal Migration and Aggregation by Reelin Signaling in the
Developing Cerebral Cortex.
AB - The mammalian cerebral neocortex has a well-organized laminar structure, achieved
by the highly coordinated control of neuronal migration. During cortical
development, excitatory neurons born near the lateral ventricle migrate radially
to reach their final positions to form the cortical plate. During this process,
dynamic changes are observed in the morphologies and migration modes, including
multipolar migration, locomotion, and terminal translocation, of the newborn
neurons. Disruption of these migration processes can result in neuronal disorders
such as lissencephaly and periventricular heterotopia. The extracellular protein,
Reelin, mainly secreted by the Cajal-Retzius neurons in the marginal zone during
development, plays a crucial role in the neuronal migration and neocortical
lamination. Reelin signaling, which exerts essential roles in the formation of
the layered neocortex, is triggered by the binding of Reelin to its receptors,
ApoER2 and VLDLR, followed by phosphorylation of the Dab1 adaptor protein.
Accumulating evidence suggests that Reelin signaling controls multiple steps of
neuronal migration, including the transition from multipolar to bipolar neurons,
terminal translocation, and termination of migration beneath the marginal zone.
In addition, it has been shown that ectopically expressed Reelin can cause
neuronal aggregation via an N-cadherin-mediated manner. This review attempts to
summarize our knowledge of the roles played by Reelin in neuronal migration and
the underlying mechanisms.
PMID- 28507984
TI - Immunoprevalence to Six Waterborne Pathogens in Beachgoers at Boqueron Beach,
Puerto Rico: Application of a Microsphere-Based Salivary Antibody Multiplex
Immunoassay.
AB - Waterborne infectious diseases are a major public health concern worldwide. Few
methods have been established that are capable of measuring human exposure to
multiple waterborne pathogens simultaneously using non-invasive samples such as
saliva. Most current methods measure exposure to only one pathogen at a time,
require large volumes of individual samples collected using invasive procedures,
and are very labor intensive. In this article, we applied a multiplex bead-based
immunoassay capable of measuring IgG antibody responses to six waterborne
pathogens simultaneously in human saliva to estimate immunoprevalence in
beachgoers at Boqueron Beach, Puerto Rico. Further, we present approaches for
determining cutoff points to assess immunoprevalence to the pathogens in the
assay. For the six pathogens studied, our results show that IgG antibodies
against antigens from noroviruses GI.I and GII.4 were more prevalent (60 and
51.6%, respectively) than Helicobacter pylori (21.4%), hepatitis A virus (20.2%),
Campylobacter jejuni (8.7%), and Toxoplasma gondii (8%) in the saliva of the
study participants. The salivary antibody multiplex immunoassay can be used to
examine immunoprevalence of specific pathogens in human populations.
PMID- 28507989
TI - Diagnostic Laparoscopy as Decision Tool for Re-recurrent Inguinal Hernia
Treatment Following Open Anterior and Laparo-Endoscopic Posterior Repair.
AB - INTRODUCTION: The guidelines of the international hernia societies recommend
posterior repair in laparo-endoscopic technique for recurrent inguinal hernia
after open anterior mesh repair and, conversely, open anterior repair for
recurrence after laparo-endoscopic primary repair. Even when these guidelines are
followed, already 1 year after repair a re-recurrence rate of 1-2% must be
expected, with that rate rising further in the subsequent years. Accordingly,
increasingly more patients with re-recurrence after anterior and posterior mesh
implantation must be treated, which constitutes a problem that to date has been
investigated in only very few studies. Hence, there are no well-founded
recommendations. This paper now presents a number of case reports aimed at
identifying the role of explorative laparoscopy as decision tool for re-recurrent
inguinal hernia treatment. PATIENTS AND METHODS: Based on three case reports the
role of explorative laparoscopy as decision tool for re-recurrent inguinal hernia
treatment is presented below. RESULTS: In all the three cases described
explorative laparoscopy played a key role as decision tool when deciding how best
to treat re-recurrence after anterior and posterior inguinal hernia repair. In
one case severe adhesions after robotic prostatectomy and in another case correct
placement of the mesh in the posterior plane, adhesions from the cecum to the
groin region and no definitive finding of a re-recurrence resulted in an open
repair. In the third case, an insufficient laparoscopic posterior mesh placement
made the re-recurrent TAPP procedure relatively easy. CONCLUSION: Explorative
laparoscopy is an important decision tool for re-recurrent inguinal hernia
treatment to minimize the risks of the procedure for the patients.
PMID- 28507987
TI - Pitx2 in Embryonic and Adult Myogenesis.
AB - Skeletal muscle is a heterogeneous tissue that represents between 30 and 38% of
the human body mass and has important functions in the organism, such as
maintaining posture, locomotor impulse, or pulmonary ventilation. The genesis of
skeletal muscle during embryonic development is a process controlled by an
elaborate regulatory network combining the interplay of extrinsic and intrinsic
regulatory mechanisms that transform myogenic precursor cells into functional
muscle fibers through a finely tuned differentiation program. However, the
capacity of generating muscle still remains once these fibers have matured. Adult
myogenesis resembles many of the embryonic morphogenetic episodes and depends on
the activation of satellite cells that have the potential to differentiate into
new muscle fibers. Pitx2 is a member of the bicoid family of homeodomain
transcription factors that play an important role in morphogenesis. In the last
decade, Pitx2 has emerged as a key element involved in the fine-tuning mechanism
that regulates skeletal-muscle development as well as the differentiation and
cell fate of satellite cells in adult muscle. Here we present an integrative view
of all aspects of embryonic and adult myogenesis in which Pitx2 is involved, from
embryonic development to satellite-cell proliferation, fate specification, and
differentiation. Those new Pitx2 functions on satellite-cell biology might open
new perspectives to develop therapeutic strategies for muscular disorders.
PMID- 28507988
TI - Comparative Therapeutic Efficacy of 153Sm-EDTMP and 177Lu-EDTMP for Bone Pain
Palliation in Patients with Skeletal Metastases: Patients' Pain Score Analysis
and Personalized Dosimetry.
AB - INTRODUCTION: The aim of the present study was to compare the therapeutic
efficacy of 153Sm-EDTMP and 177Lu-EDTMP in pain palliation in cancer patients
with skeletal metastases. MATERIALS AND METHODS: Thirty patients (25 M:5 F, mean
age: 66.0 +/- 14.7 years) of breast/prostate cancer with documented skeletal
metastases were recruited prospectively. Twenty patients were considered randomly
for treatment with 153Sm-EDTMP and with 177Lu-EDTMP in 10 patients, respectively.
Using fixed dose of 37.0 MBq/kg body weight of each, the mean administered doses
of 153Sm-EDTMP and 177Lu-EDTMP were 2,155.2 +/- 419.6 MBq (1,347-2,857) and
1,935.1 +/- 559.4 MBq (1,073-2,627), respectively. Anterior and posterior whole
body images were acquired at different time points following radioactivity
administration. The first data set of pre-void images (acquired at 0.5 h)
representing the total activity of either of 153Sm-EDTMP or 177Lu-EDTMP was
considered as reference images. All the serial images were used for patients'
dosimetry analysis by using organ level internal dosimetry assessment algorithm.
Reduction in pain scoring was assessed clinically over 8 weeks by using
appropriate WHO criteria and correlated with the absorbed dose to the metastatic
sites. RESULTS: A total of 86 metastatic lesions clearly visualized on post
therapy serial images (matching on bone scans) were evaluated for absorbed dose
calculations. Both 153Sm-EDTMP and 177Lu-EDTMP delivered similar absorbed dose to
the metastatic sites, i.e., 6.22 +/- 4.21 and 6.92 +/- 3.92 mSv/MBq,
respectively. The mean absorbed doses to various other organs were found to be
comparable and within the safe limits. A complete response (CR) for each
radionuclide was evaluated as 80.0%. No significant alternation in blood
parameters and no untoward reaction were observed. However, a mild to severe
toxicity was observed in two patients (1 each with 153Sm-EDTMP and 177Lu-EDTMP).
Kaplan-Meier survival analysis demonstrated that 27/30 patients had pain-free
survival (CR) up to the observational period of 8 weeks. However, no
statistically significant correlation could be established between the pain
scoring and absorbed dose to metastatic sites. CONCLUSION: Both the radionuclides
thus offer an effective and comparable therapeutic efficacy for bone pain
palliation at an affordable cost and can be used interchangeably as per the
availability.
PMID- 28507986
TI - More than Just a Simple Cardiac Envelope; Cellular Contributions of the
Epicardium.
AB - The adult pumping heart is formed by distinct tissue layers. From inside to
outside, the heart is composed by an internal endothelial layer, dubbed the
endocardium, a thick myocardial component which supports the pumping capacity of
the heart and exteriorly covered by a thin mesothelial layer named the
epicardium. Cardiac insults such as coronary artery obstruction lead to ischemia
and thus to an irreversible damage of the myocardial layer, provoking in many
cases heart failure and death. Thus, searching for new pathways to regenerate the
myocardium is an urgent biomedical need. Interestingly, the capacity of heart
regeneration is present in other species, ranging from fishes to neonatal
mammals. In this context, several lines of evidences demonstrated a key
regulatory role for the epicardial layer. In this manuscript, we provide a state
of-the-art review on the developmental process leading to the formation of the
epicardium, the distinct pathways controlling epicardial precursor cell
specification and determination and current evidences on the regenerative
potential of the epicardium to heal the injured heart.
PMID- 28507992
TI - Current Concepts and Advancements in Management of Traumatic Brain Injury; A
Glimpse at the Recently Published Evidence.
PMID- 28507990
TI - Development of an Online, Evidence-Based Patient Information Portal for
Congenital Heart Disease: A Pilot Study.
AB - OBJECTIVES: In response to an increased need for patient information on
congenital heart disease in the Netherlands, we initiated a nationwide initiative
to develop an online, evidence-based patient information portal, starting with a
pilot project aimed at the subgroup of patients with congenital aortic and
pulmonary valve disease. METHODS AND RESULTS: We developed an information portal
that aims to (1) improve patient knowledge and involvement and to subsequently
reduce anxiety and decisional conflict and improve mental quality of life and (2)
to support physicians in informing and communicating with their patients. The
information portal was developed according to the systematic International
Patient Decision Aid Standards development process employing Delphi techniques by
a multidisciplinary workgroup of pediatric and adult congenital cardiologists, a
congenital cardiothoracic surgeon, a psychologist, an epidemiologist, a patient
representative, and web and industrial design experts. First, patients and
physicians were surveyed and interviewed to assess the current state of patient
information and explore their preferences and needs to determine the focus for
the development of the information portal. We found that patient knowledge and
numeracy are limited, reliable information is scarce, physicians inform patients
selectively and patient involvement is suboptimal, and there is a need for more
reliable, tailored, and multi-faceted information. Based on the findings of these
surveys and interviews, a patient-tailored information portal was designed that
presents evidence-based disease- and age-specific medical and psychosocial
information about diagnosis, treatment, prognosis, and impact on daily life in a
manner that is comprehensible and digestible for patients and that meets the
needs expressed by both patients and physicians. The effect of the website on
patient outcome is currently being assessed in a multicenter stepped-wedge
implementation trial. CONCLUSION: The present pilot project succeeded in
developing an online, evidence-based information portal that is supported by both
patients and physicians. The information portal will be further developed and
expanded to include all other major forms of congenital heart disease,
translations into other languages, and a public information portal to serve
patients' relatives and the general public at large.
PMID- 28507991
TI - Evaluation of Bioequivalence of Two Long-Acting 20% Oxytetracycline Formulations
in Pigs.
AB - The aim of this study was to explore the bioequivalence of long-acting
oxytetracycline in two formulations, a reference formulation (Terramycin 20% LA,
Pfizer) and a test one (Kangtekang 20% LA, Huishen). Both formulations were
administered intramuscularly at 20 mg/kg body weight at each of 24 healthy
animals during a two-period crossover parallel experimental design. The
oxytetracycline (OTC) concentrations in plasma were measured by high-performance
liquid chromatography, and the limit of quantification was 0.05 ug/ml with a
recovery ratio of above 90%. Moreover, the descriptive pharmacokinetics
parameters (Cmax, AUC0-144h, and AUC0-infinity) were calculated and compared
under analysis of variance, and 90% confidence interval (CI) were compared,
except for Tmax analyzed by non-parametric tests based on Wilcoxons's signed rank
test. The comparison results of Cmax, AUC0-144h, AUC0-infinity, and Tmax were
5.066 +/- 0.486, 5.071 +/- 0.877 ug/ml, 118.926 +/- 13.259, 126.179 +/- 17.390 ug
h/ml, 123.087 +/- 13.906, 130.732 +/- 18.562 ug h/ml, 0.740 +/- 0.278, 0.650 +/-
0.258 h, respectively, and did not reveal any significant differences. In
addition, 90% CIs of these ratios for reference and test product were within an
interval of 80-125%, and the relative bioavailability of test one was (94.291 +/-
15.287)%. Therefore, it has been concluded that test OTC was bioequivalent to the
reference formulation in pigs.
PMID- 28507994
TI - A Step-by-Step Framework on Discrete Events Simulation in Emergency Department; A
Systematic Review.
AB - OBJECTIVE: To systematically review the current literature of simulation in
healthcare including the structured steps in the emergency healthcare sector by
proposing a framework for simulation in the emergency department. METHODS: For
the purpose of collecting the data, PubMed and ACM databases were used between
the years 2003 and 2013. The inclusion criteria were to select English-written
articles available in full text with the closest objectives from among a total of
54 articles retrieved from the databases. Subsequently, 11 articles were selected
for further analysis. RESULTS: The studies focused on the reduction of waiting
time and patient stay, optimization of resources allocation, creation of crisis
and maximum demand scenarios, identification of overcrowding bottlenecks,
investigation of the impact of other systems on the existing system, and
improvement of the system operations and functions. Subsequently, 10 simulation
steps were derived from the relevant studies after an expert's evaluation.
CONCLUSION: The 10-steps approach proposed on the basis of the selected studies
provides simulation and planning specialists with a structured method for both
analyzing problems and choosing best-case scenarios. Moreover, following this
framework systematically enables the development of design processes as well as
software implementation of simulation problems.
PMID- 28507993
TI - Enhanced Recovery after Emergency Surgery: A Systematic Review.
AB - OBJECTIVE: To evaluate the current scientific evidence for the applicability,
safety and effectiveness of pathways of enhanced recovery after emergency surgery
(ERAS). METHODS: We undertook a search using PubMed and Cochrane databases for
ERAS protocols in emergency cases. The search generated 65 titles; after
eliminating the papers not meeting search criteria, we selected 4 cohort studies
and 1 randomized clinical trial (RCT). Data extracted for analysis consisted of:
patient age, type of surgery performed, ERAS elements implemented, surgical
outcomes in terms of postoperative complications, mortality, length of stay (LOS)
and readmission rate. RESULTS: The number of ERAS items applied was good, ranging
from 11 to 18 of the 20 recommended by the ERAS Society. The implementation
resulted in fewer postoperative complications. LOS for ES patients was shorter
when compared to conventional care. Mortality, specifically reported in three
studies, was equal or lower with ERAS. Readmission rates varied widely and were
generally higher for the intervention group but without statistical significance.
CONCLUSIONS: The studies reviewed agreed that ERAS in emergency surgery (ES) was
feasible and safe with generally better outcomes. Lower compliance with some of
the ERAS items shows the need for the protocol to be adapted to ES patients. More
evidence is clearly required as to what can improve outcomes and how this can be
formulated into an effective care pathway for the heterogeneous ES patient.
PMID- 28507995
TI - The Necessity of Data Mining in Clinical Emergency Medicine; A Narrative Review
of the Current Literatrue.
PMID- 28507996
TI - Effects of Pulsed Electromagnetic Field with Predatory Stress on Functional and
Histological Index of Injured-Sciatic Nerve in Rat.
AB - OBJECTIVE: To assess the effect of combination of pulsed electromagnetic fields
(PEMF) with predatory stress on transected sciatic nerve regeneration in rats.
METHODS: In sham- operated group (SOG) the nerve was manipulated and left intact.
The 10-mm rat sciatic nerve gap was created in rats. In transected group
(Transected) nerve stumps were sutured to adjacent muscle and in vein graft group
(VG) the gap was bridged using an inside-out vein graft. In VG/PEMF group the
transected nerve was bridged using vein graft, phosphate buffered saline was
administered into the graft and the whole body was exposed to PEMF. In VG/PS
group the transected nerve was bridged using vein graft, phosphate buffered
saline was administered into the graft and the rats underwent predatory stress
(PS). In VG/PEMF/PS group the transected nerve was bridged using vein graft,
phosphate buffered saline was administered into the graft, the whole body was
exposed to PEMF and the rats underwent predatory stress. The regenerated nerve
fibers were studied within 12 weeks after surgery. RESULTS: Functional,
gastrocnemius muscle mass findings and morphometric indices confirmed faster
recovery of regenerated axons in VG/PEMF and VG/PEMF/PS groups compared to those
in the other groups (p=0.001). The whole body exposure to PEMF improved
functional recovery. Predatory stress did not affect nerve regeneration in the
animals undergone predatory stress (p=0.343). CONCLUSION: Pulsed electromagnetic
fields could be considered as an effective, safe and tolerable treatment for
peripheral nerve repair in clinical practice.
PMID- 28507997
TI - Recognizing Sudden Cardiac Arrest May Require More Than Two Questions during
Telephone Triage: Developing a Complementary Checklist.
AB - OBJECTIVE: To develop decision-support tools to identify patients experiencing
sudden cardiac arrest (SCA). METHODS: Eighty calls related to SCA were content
analyzed, and the contextual patterns that emerged were organized into a
checklist. Two researchers independently analyzed the recorded calls and compared
their findings. Eighteen dispatchers scored 20 cases (which included SCA and non
SCA cases) both with and without the checklist. Correct responses for each case
and agreement among dispatchers have been reported. RESULTS: Eighty audio files
(total time, 96 min) were analyzed, and a total of 602 codes were extracted from
the text and recordings. The caller's tone of voice and presence or absence of
background voices, calling for an ambulance and giving the dispatcher the address
promptly, and description of the primary complaint and respirations accounted for
38%, 39%, and 23% of all codes, respectively. A 15-item complementary checklist
has been developed. The mean percentages of correct responses were 66.9%+27.96%
prior to the use of checklist and 80.05%+10.84% afterwards. Results of the
independent t test for checklist scores showed that statistically significant
differences were present between the SCA and non-SCA cases (t=5.88, df=18,
p=0.000). CONCLUSION: Decision support tools can potentially increase the
recognition rate of SCA cases, and therefore produce a higher rate of dispatcher
directed CPR.
PMID- 28507998
TI - Effects of Pre-Injury Anti-Platelet Agents on Short-Term Outcome of Patients with
Mild Traumatic Brain Injury: A Cohort Study.
AB - OBJECTIVE: To determine the effects of pre-injury consumption of anti-platelet
agents on the 30-day outcomes of patients with mild traumatic brain injury (TBI).
METHODS: This prospective cohort study was conducted at three general hospitals
in Tehran, Iran between July 2013 and July 2014. The study population included
all patients with mild TBI aged over 18 years that medicated with aspirin or
clopidogrel before occurring trauma. Within hospitalization, all patients were
assessed with respect to in-hospital conditions especially complications and
adverse events. After discharge, the individuals were followed for 30 days by
telephone to assess mortality and disability using the Glasgow outcome scale
(GOS). RESULTS: Of 1140 patients with mild TBI, only 135 had previously received
aspirin and/or clopidogrel. The mean age was dramatically higher in those who
were taking aspirin or clopidogrel (p<0.001). The patients with previously use of
anti-platelets were more transferred by ambulance when compared to another group
(p=0.006). The patients on anti-platelets had significantly lower GCS on
admission when compared to others (p<0.001). Length of hospitalization was
significantly longer in those receiving anti-platelets (p=0.003). In follow-up,
30-day mortality and disability was revealed in 2.8% of patients that received
only aspirin and 7.5% in aspirin with clopidogrel and in 1.6 % of those who did
not receive drugs without any significant difference between aspirin and control
group (p=0.208) and significant difference in aspirin with clopidogrel group
(p<0.001). CONCLUSION: The premedication by anti-platelets (aspirin and/or
clopidogrel) in patients with mild TBI leads to prolonged hospital stay, and
increase rate of disability. Age and on admission GCS are the independent risk
factors for predicting the outcome in patients with mild TBI receiving anti
platelet agents.
PMID- 28507999
TI - Risk Factors of Road Traffic Accidents Associated Mortality in Northern Iran; A
Single Center Experience Utilizing Oaxaca Blinder Decomposition.
AB - OBJECTIVES: To investigate the differences in death after receiving emergency
services in traffic accidents between urban and rural regions, and decompose
factors of the gap in Langerood, Northern Iran. METHODS: This cross-sectional
study was conducted in Langrood, Northern Iran during a 1-year period from 2013
to 2014. The hospital data of traffic crashes were used. Data contained those
patients who survived at the scene of accident. Injury severity score, time to
admission, age, gender, season of crash and type of collision were variables used
in this study. Oaxaca decomposition technique was used to show the amount of
inequity. In addition, three regression models were used to show the reason of
inequity. RESULTS: Overall 1520 patients with road traffic accidents were
admitted to our center during the study period. The mean age of the patients was
35.45 +/- 17.9 years, and there were 1158 (76.1 %) men among the victims.
Motorbike accidents accounted for 869 (57.1%) injuries and 833 (54.8 %) accidents
occurred in rural regions. The in-hospital mortality rate was 60 (3.9%). The
results of this study showed that 95% of inequity came from factors used in this
study and 2.04% disadvantages were for rural crashes. Severity of crash and time
to admission had relationship with death, while the effects of time to admission
was higher in rural region and severity of the accident had more effect on
mortality in urban regions in comparison with rural ones. CONCLUSION: The high
rate of fatal accidents could be decreased by deleting the gap of access to
health care services between urban and rural regions. This study suggested that
more efforts of health system are needed to reduce the gap.
PMID- 28508000
TI - Knowledge and Attitude of Iranian Red Crescent Society Volunteers in Dealing with
Chemical Attacks.
AB - OBJECTIVE: To evaluate the knowledge, attitude, and preparedness of Mahabad Red
Crescent Society volunteers in dealing with chemical attacks. METHODS: This
prospective cross-sectional study was conducted on 120 Red Crescent Society
volunteers in Mahabad City, Iran, during 2014-2015.The knowledge of the
volunteers was evaluated and rated using a questionnaire as poor, moderate, and
good. Also, the attitude of the volunteers towards the chemical attacks and their
preparedness were rated as appropriate and inappropriate using a questionnaire.
Data were analyzed using the SPSS software version 21. RESULTS: From a total of
120 volunteers, 62.5% were males. The mean age of the volunteers was 32.0 +/- 8.2
years. None of the volunteers had adequate knowledge regarding management of the
consequences of chemical terrorist attacks. Only 10 volunteers (8.3%) had
appropriate attitude and 7 (5.8%) stated their preparedness for being sent to the
crisis zone. Also, 116 volunteers (96.7%) declared that Mahabad Red Crescent
Society has an inappropriate level of preparedness to encounter chemical
terrorism attacks and release of chemical agents related to petrochemical
industrial chlorine resources into the water and wastewater. CONCLUSION: The
findings of the present study show poor knowledge and inappropriate attitude of
Mahabad Red Crescent Society volunteers, and rescuers in encountering probable
chemical attacks and industrial accidents. Furthermore, the Red Crescent Society
had an inappropriate level of preparedness in the field of chemical terrorism
from the viewpoint of the studied volunteers.
PMID- 28508001
TI - Closing a Tracheal Defect with an Omental Pedicled Gastric Flap; A Technical
Note.
AB - Due to an adenocarcinoma of the right upper lobe with infiltration of the main
bronchus a 49-years-old female patient underwent an upper bilobectomy with sleeve
resection. After two completed chemotherapy bouts and signs of sepsis another
thoracotomy was inevitable. As a complicating factor a supracarinal, necrotic
and perforating lesion of the trachea appeared. The defect can be initially
repaired with a suture and covered with azygos vein material. However surgical
revision showed an enlargement of the tracheal necrosis. Then the lesion was
occluded with a diaphragmatic pedicled flap. Nevertheless after the operation a
tracheal insufficiency with massive ventilation leakage was observed. It was
generated by the death of the diaphragmatic flap. As an ultimate therapeutic
measure a transplantation of a pedicled omental gastric flap was performed, which
in case of a failure of the conventional operative techniques, is an additional
option in closing tracheal defects caused by infections. Especially in cases of
massive infected thoracic cavity and tracheal necrosis omentum majus is, compared
to muscle flaps, the better biological tissue to close and heal the tracheal
defect. This case report firstly describes a successfully closure of a tracheal
defect using the technique mentioned above.
PMID- 28508002
TI - Postoperative Spontaneous Intussusception Caused by a Jejunal Peritoneal Cyst: A
Case Report and Literature Review.
AB - Postoperative intussusception in adults is an extremely rare clinical entity.
Postoperative intussusception caused by a jejunal peritoneal cyst is even rarer.
Etiopathogenesis of this clinical condition is not well understood. In the given
case it seems to be a complication of prolonged contact of a draining tube with
bowel. We present a case of postoperative spontaneous intussusception in a 72
year-old female patient after gastric surgery. The cause of intussusception
appeared to be a jejunal peritoneal cyst which is extremely rare. Desinvagination
and excision of cyst via laparotomy was performed and the postoperative course
was uneventful. Abdominal draining tubes should be placed in a position which
will avoid possible further prolonged contact with bowel.
PMID- 28508003
TI - Avoidance of 'Mishra Phenomenon' Prevents Technical Failure of Hepatic Artery
Angioembolization following Failed Perihepatic Packing in Traumatic Liver Injury.
PMID- 28508005
TI - An Unusual First Manifestation of Hodgkin Lymphoma: Epitrochlear Lymph Node
Involvement-A Case Report and Brief Review of Literature.
AB - Although epitrochlear lymph nodes may be enlarged as a part of generalized
lymphadenopathy, isolated enlargement of epitrochlear lymph nodes is rarely seen.
We describe Hodgkin's lymphoma in a 55-year-old male who presented with isolated
epitrochlear lymphadenopathy of his right arm. In the histopathological
examination of the epitrochlear lymph node was a lymphocyte-rich Hodgkin lymphoma
with a clinical grade (CS IA) diagnosed. The diagnosis was confirmed, via the
bone marrow biopsy and positron emission tomography/computed tomography imaging,
as pathological stage PS IA and clinical stage CS IA. Epitrochlear lymph node
involvement, as a first presentation, is rarely seen in Hodgkin's lymphoma. The
aim of this study was to recapitulate the possible background diseases arising on
the basis of an asymptomatic epitrochlear lymphadenopathy, to review the Hodgkin
lymphoma presenting with primary epitrochlear lymphadenopathy in light of the
literature, and to highlight the importance of a careful examination of the elbow
site in routine physical examination.
PMID- 28508004
TI - Tacrolimus-Associated Dilated Cardiomyopathy in Adult Patient After Orthotopic
Liver Transplant.
AB - This report presents a case of tacrolimus cardiotoxicity in an adult patient who
received tacrolimus immunosuppression for orthotopic liver transplant (OLT).
Tacrolimus-associated cardiotoxicity has been described in the literature,
however this is the first case to document the development of a dilated
cardiomyopathy in a patient shortly after initiating tacrolimus therapy post
transplant. With the growing use of tacrolimus in transplant medicine, this case
report expands the literature of tacrolimus cardiotoxicity and can aid clinicians
in the evaluation and management of patients exposed to this form of
immunosuppression.
PMID- 28508007
TI - Five-Year Outcomes After Treatment for Acute Instability of the Tibiofibular
Syndesmosis Using a Suture-Button Fixation System.
AB - BACKGROUND: Suture-button repair is a widely accepted surgical treatment for
acute and isolated ankle syndesmosis injuries. To our knowledge, midterm results
have not previously been reported. PURPOSE: To evaluate the clinical,
qualitative, and quantitative radiological midterm outcomes of suture-button
repair after acute isolated ankle syndesmosis injuries. STUDY DESIGN:
Retrospective case series; Level of evidence, 4. METHODS: Clinical outcomes were
measured using the Foot and Ankle Disability Index (FADI) and the American
Orthopaedic Foot and Ankle Society (AOFAS) score. Three-tesla magnetic resonance
imaging (MRI) was performed bilaterally at the ankle. Besides morphological
sequences for evaluation of the syndesmosis and degenerative changes of the ankle
using the Ankle Osteoarthritis Scoring System (AOSS), the MR protocol included a
coronal 2-dimensional multislice multiecho sequence for quantitative cartilage T2
weighted mapping. Spearman correlations and paired t tests were used for
statistical analysis. RESULTS: This retrospective study included 19 consecutive
patients (mean age, 29.7 +/- 11.5 years) with acute isolated syndesmosis injuries
treated with a suture-button system between January 2006 and June 2014, with a
mean follow-up of 5.1 +/- 2.6 years. Postoperatively, the median FADI score was
136 (range, 78-136), and the median AOFAS score was 100 (range, 87-100).
Seventeen (89.5%) patients reported to have reached their preinjury level of
sports activities. MRIs of 16 patients were obtained and all showed intact
anterior and posterior syndesmotic ligaments; however, in most patients, the
previously injured syndesmotic ligament was thickened compared with the uninjured
ankle. Average width of the anterior (P = .81) and posterior (P = .60)
syndesmosis was not significantly different between the ipsilateral (3.2 +/- 1.2
and 4.4 +/- 0.9 mm) and contralateral ankles (3.0 +/- 0.6 and 4.2 +/- 0.7 mm).
The median AOSS score was 1.5 (range, 0-11) for the ipsilateral ankle and 0
(range, 0-6) for the contralateral ankle. T2 values of articular cartilage did
not significantly differ between the involved and the uninjured ankle (P = .68).
Five patients needed hardware removal due to persistent skin irritation, and 1
patient suffered from reinstability of the ankle resulting in revision surgery 2
years after the index surgery. CONCLUSION: Suture-button fixation is an excellent
treatment for acute and isolated syndesmosis injuries, resulting in stable ankles
without early or advanced osteoarthritic changes at midterm follow-up.
PMID- 28508006
TI - Early Osteoarthritis After Untreated Anterior Meniscal Root Tears: An In Vivo
Animal Study.
AB - BACKGROUND: Meniscal root tears cause menisci and their insertions to
inadequately distribute loads and potentially leave underlying articular
cartilage unprotected. Untreated meniscal root tears are becoming increasingly
recognized to induce joint degradation; however, little information is known
about anterior meniscal root tears and how they affect joint tissue. PURPOSE: To
observe the early degenerative changes within the synovial fluid, menisci, tibial
articular cartilage, and subchondral bone after arthroscopic creation of
untreated anterior meniscal root tears. STUDY DESIGN: Controlled laboratory
study. METHODS: Anterolateral meniscal root tears were created in 1 knee joint of
5 adult Flemish Giant rabbits, and anteromedial meniscal root tears were created
in 4 additional rabbits. The contralateral limbs were used as nonoperated
controls. The animals were euthanized at 8 weeks postoperatively; synovial fluid
was aspirated, and tissue samples of menisci and tibial articular cartilage were
collected and processed for multiple analyses to detect signs of early
degeneration. RESULTS: Significant changes were found within the synovial fluid,
meniscal tissue, and tibial subchondral bone of the knees with anterior meniscal
root tears when compared with controls. There were no significant changes
identified in the tibial articular cartilage when comparing the tear groups with
controls. CONCLUSION: This study demonstrated early degenerative changes within
the synovial fluid, menisci, and tibial subchondral bone when leaving anterior
meniscal root tears untreated for 8 weeks. The results suggest that meniscal
tissue presents measurable, degenerative changes prior to changes within the
articular cartilage after anterior meniscal root tears. Anterior destabilization
of the meniscus arthroscopically may lead to measurable degenerative changes and
be useful for future in vivo natural history and animal repair studies. CLINICAL
RELEVANCE: The present study is the first to investigate various tissue changes
after anterior meniscal root tears of both the medial and lateral menisci. The
results from this study suggest that degenerative changes occur within the
synovial fluid, meniscus, and tibial subchondral bone prior to any measurable
changes to the tibial articular cartilage. Further studies should expand on this
study to evaluate how these components continue to progress when left untreated
for long periods.
PMID- 28508009
TI - Encephalomyelitis Following Definitive Zika Virus Infection.
PMID- 28508010
TI - Spontaneous remission lasting more than a decade in untreated AQP4 antibody
positive NMOSD.
PMID- 28508008
TI - The Coracoacromial Ligament: Anatomy, Function, and Clinical Significance.
AB - The coracoacromial ligament (CAL) was first described as a pain generator by Dr
Charles Neer in the early 1970s. Since that time, considerable controversy
regarding CAL management during acromioplasty has persisted. This review aims to
better understand the role of the CAL in shoulder physiology and pathology. Sixty
six articles from 1958 to 2016 were identified using an electronic search of
PubMed, Cochrane Library, AccessMedicine, and MD Consult for case series as well
as cohort and prospective studies. The authors used "coracoacromial ligament" and
"coracoacromial veil" as medical subject headings (MeSH). In addition, reference
lists from all identified articles were reviewed for studies that the search
terms may have omitted. The CAL plays an important role in shoulder biomechanics,
joint stability, and proprioception. Morphological variance of the CAL is evident
throughout the literature. Age-dependent changes due to chronic stress and
cellular degradation cause thickening and stiffening of the CAL that may
contribute to a spectrum of shoulder pathology from capsular tightness to rotator
cuff tear arthropathy and impingement syndrome. The CAL is an integral component
of the coracoacromial arch. CAL release during acromioplasty remains
controversial. Future clinical outcomes research should endeavor to advance the
understanding of the CAL to refine clinical and intraoperative decision making
regarding its management.
PMID- 28508011
TI - Mandated Health Insurance and Provider Reimbursement via Private Insurance:
Evidence From the Massachusetts Health Reform.
AB - In 2006, Massachusetts passed a reform that required individuals to purchase
health insurance and provided subsidized health insurance to low-income
individuals. The US Patient Protection and Affordable Care Act (ACA) was modeled
after this reform, making Massachusetts an ideal place to look at potential
outcomes from the ACA. Postreform, the proportion of the health-insured
population in Massachusetts greatly increased, which potentially changed
physician reimbursement for procedures as usage of care, particularly
preventative care for children increased. We find that reimbursement for well
infant visits rose temporarily by approximately 4% the year after the reform but
that the effective price increase did not persist. It is likely that this lack of
persistence is due to an increase in the supply of physicians. This has important
implications for the ACA, as expanding physician capacity is more difficult on a
national level.
PMID- 28508012
TI - Rehabilitation of Discharged Patients With Chronic Obstructive Pulmonary Disease
Are New Strategies Needed?
AB - BACKGROUND: Rehabilitation after hospital stay implies several benefits for
patients with chronic obstructive pulmonary disease (COPD); still few patients
are referred and participate in rehabilitation programs. We conducted a case
study to investigate the effects of interventions targeting the referral, uptake,
and completion for a program of early rehabilitation in the primary health-care
sector. METHODS: We undertook targeted initiatives to make patients participate
in an individualized rehabilitation program with gradual increased intensity.
After discharge, primary care COPD nurses and physiotherapists guided patients
through progressing exercises in small groups online. Patients proceeded to class
based exercises, patient education and/or leisure activities, or continued
telerehabilitation. We evaluated the effects of the intervention by assessing
referral rates, completion, and readmission. RESULTS: Sixteen (23% of discharged
patients) patients were referred to rehabilitation. In comparison, only 1 (0.8%)
in 131 patients from Vejle hospital was referred to Vejle hospital. Twelve
patients completed rehabilitation, all having severe COPD. All started the
program within 2 weeks and proceeded to the online-guided exercises within 4
weeks. Study data showed that after 30 days, 1 (6.3%) of the 16 patients in the
rehabilitation program had been readmitted compared to 8 (14.8%) of 55 patients
who were not referred. After 90 days, 2 (12.5%) and 11 (20.0%) patients were
readmitted, respectively. The readmission rate showed a nonsignificant decline in
patients participating in rehabilitation. CONCLUSION: This case study showed that
the referral rate of patients with COPD to early municipal rehabilitation is
extremely low without a targeted effort and still insufficient in spite of a
focused intervention. We showed that completion of a municipal rehabilitation
program shortly after discharge is possible even for patients with severe COPD.
The findings from our pilot study can guide further investigations into the
effect of implementation strategies for handovers between health-care sectors to
secure early-onset rehabilitation of patients with COPD.
PMID- 28508013
TI - Self-Reported Diagnosis of Type 1 and Type 2 Diabetes and Lifestyle Change Among
Uninsured Primary Care Patients.
AB - INTRODUCTION: The purpose of this study is to examine self-reported diagnosis of
type 1 and type 2 diabetes and lifestyle change among uninsured primary care
patients utilizing a free clinic. METHODS: Free clinic patients participated in a
self-administered survey in May and June 2016. Patients with the following self
reported diagnoses were analyzed: type 2 diabetes only (n = 84), and type 1
diabetes only or both (n = 43). RESULTS: Participants who reported having type 2
diabetes only and/or were patients of the diabetes clinic were less likely to
have modified diet and/or physical activity to manage diabetes compared to those
with type 1 diabetes and/or those who were not patients of the diabetes clinic.
Participants with hypertension were more likely to have changed diet and/or
physical activity compared to those without hypertension. CONCLUSION: Uninsured
primary care patients may not know whether they have type 1 or type 2 diabetes.
This is problematic as type 1 and type 2 diabetes require different prevention
and self-management strategies. Future studies should examine the impact of
misunderstanding the 2 types of diabetes on health behaviors and outcomes and
explore the context of the misunderstanding.
PMID- 28508014
TI - When Actions Speak Louder Than Words: Extending the Reach of Qualitative Data
Collecting.
AB - Through the lens of a study exploring dementia care partnering, the purpose of
this methods article is to focus on the role of artifacts and embodied data in
data collection. In addition, it illustrates how to use a range of data
collecting methods. The article identifies benefits of additional data collecting
methods to research and care. These include the need to expand data collecting
methods beyond spoken word, integrate a range of data collecting approaches into
research courses across disciplines, increase support of qualitative research,
and advocate for greater inclusivity in research. Data collecting approaches can
also have implications for quality of life among persons often excluded from
research-building endeavors. They can contribute to the unfolding of new
findings, which can influence care practices.
PMID- 28508015
TI - Vaccine-Hesitant Justifications: "Too Many, Too Soon," Narrative Persuasion, and
the Conflation of Expertise.
AB - Vaccine-preventable diseases have re-emerged as more individuals have strayed
from the recommended inoculation schedule. Previous work on vaccine hesitancy is
generally limited to content analyses. Using grounded theory, this project
examines vaccine debates on a prominent discussion board over a period of five
years. Individuals generally justified opposition or hesitancy toward vaccines
through personal experience and/or research, and the concepts of narrative
persuasion and the conflation of expertise help describe the most prominent
characteristics of such discourse. A consideration of online comments regarding
vaccinations allows practitioners to not only become better prepared for patient
concerns they might encounter, and but also become more familiar with the types
of anecdotes and narratives that may be influential but left unspoken in face-to
face conversations.
PMID- 28508016
TI - Trust, Health Care Relationships, and Chronic Illness: A Theoretical Coalescence.
AB - Trust in health care relationships is a key ingredient of effective, high-quality
care. Although the indirect influence of trust on health outcomes has long been
recognized, recent research has shown that trust has a direct effect on outcomes
of care. Trust is important. However, the research on trust is disparate,
organized around differing definitions, and primarily focused on patients' trust
in physicians. Morse's method of theoretical coalescence was used to further
develop and elaborate a grounded theory of the evolution of trust in health care
relationships, in the context of chronic illness. This middle-range theory offers
a clear conceptual framework for organizing and relating disparate studies,
explaining the findings of different studies at a higher conceptual level, and
identifying gaps in research and understanding. In addition, the grounded theory
is relevant to practice.
PMID- 28508017
TI - Caring for Clients and Families With Anxiety: Home Care Nurses' Practice
Narratives.
AB - This study elucidated Japanese home care nurses' experiences of supporting
clients and families with anxiety. We interviewed 10 registered nurses working in
home care agencies and analyzed the data using grounded theory to derive
categories pertaining to the nurses' experiences of providing care. We
conceptualized nurses' approaches to caring for anxiety into three categories:
First, they attempted to reach out for anxiety even when the client/family did
not make it explicit; second, they tried to alter the outlook of the situation;
and third, they created comfort in the lives of the client/family. The
conceptualizations of nurses' strategies to alleviate client/family anxiety may
reflect Japanese/Eastern cultural characteristics in communication and their view
of the person and social care system, but these conceptualizations may also
inform the practice of Western nurses by increasing awareness of skills they may
also have and use.
PMID- 28508018
TI - Conflict and Care: Israeli Healthcare Providers and Syrian Patients and
Caregivers in Israel.
AB - Israel has provided immediate healthcare to Syrian children, civilians and
fighters since early 2013 despite being in an official state of war with Syria
since 1973. We present qualitative findings from a larger mixed-methods
phenomenological study to understand how the geopolitical and social history of
Israel and Syria influences healthcare providers and Syrian patient caregivers in
northern Israel. Theories of humanization and cognitive dissonance guided this
study and frame the beliefs and experiences of healthcare providers who treated
wounded Syrians in Israeli hospitals. Findings indicate healthcare providers and
Syrian caregivers adjusted their beliefs to allow for positive healthcare
experiences. Qualitative analysis revealed two major themes: supportive and
hindering systemic elements contributing to the healthcare provider-patient
caregiver relationship. Internal psychological developments, contextual factors,
and relational processes influenced humanization of the other within the
relationship. This study illuminates unique ethical and humanitarian demands
relevant for healthcare workers and those with whom they interact.
PMID- 28508019
TI - "I Do It With Love": Engagement in Caring for People With Dementia.
AB - For caregivers, the impacts of caring for their loved ones with dementia at home
are complex. The purpose of this study was to gain understanding of the meaning
and experience of engagement for caregivers of individuals with dementia living
in the community. Participants are from a culturally diverse population of low
income caregivers and care recipients in the northeastern United States. We
conducted in-depth semi-structured interviews with caregivers (n = 17) who were
caring for parents, friends, or other relatives with dementia. We used
interpretative phenomenological analysis and identified the superordinate themes
of connectedness, meaningfulness, acceptance, and vigilance. We conclude that
caregiver engagement is a multidimensional phenomenon, with some dimensions being
contextual and specific to caregiving. It is a relational concept, referring to a
committed, vigilant, and meaningful relationship of caregivers and care
recipients as active collaborators. The different aspects of engagement can
complement each other, or they can be in contradiction.
PMID- 28508020
TI - Birth Care Providers' Experiences and Practices in a Brazilian Alongside
Midwifery Unit: An Ethnographic Study.
AB - The implementation of a new birthing facility in a country such as Brazil
requires an extensive in-depth analysis of the challenges faced. The aim of this
study was to explore beliefs, values, experiences, and practices related to the
provision of birthing and neonatal care with the implementation of a new birth
care facility structure called alongside midwifery units in Brazil. The study
utilizes an ethnographic method to evaluate members of a Brazilian public
hospital's midwifery unit. The ethnographic study focuses on the cultural theme
of "between the proposed and the possible": the following birthing care
guidelines require overcoming numerous obstacles, and four other cultural
subthemes toward revealing the analyzed birth care team's perspectives. The study
found that prior training and preparation of all members of the care team, as
well as the provision of adequate institutional infrastructure are essential for
the implementation of a new and innovative birthing care center.
PMID- 28508021
TI - Examining the Roles and Experiences of Fathers of Children With Chronic Kidney
Disease.
AB - This study examined roles and experiences of fathers of children with chronic
kidney disease (CKD). Based on interpretive description, semistructured
interviews were conducted with 22 fathers of children receiving a range of
treatments (transplant, peritoneal dialysis, hemodialysis, and CKD not requiring
renal replacement therapy). Fathers described various experiences and means of
adjusting to shifts associated with pediatric CKD. These included loss of
personal control, a sense of personal isolation, and a stance of remaining strong
amidst personal suffering. Nuanced differences according to modality of CKD care
were identified. Fathers engaged in strategies that fostered coping, such as
remaining positive and taking charge. They conveyed deep love for their child,
and demonstrated ingenuity and persistence in care. Few resources of support were
accessed by fathers. Study recommendations invite holistic approaches to health
care, with improved resources for families-including fathers-in addressing the
needs of this population.
PMID- 28508022
TI - Impact of Health Literacy on Senior Citizen Engagement in Health Care IT Usage.
AB - Objective: Patient engagement in health care information technology (IT) is
required for government reimbursement programs. This research surveyed one older
adult group to determine their willingness to use health information from a
variety of sources. Health literacy was also measured using the Newest Vital Sign
(NVS) and eHealth Literacy Scale (eHEALS) tools. Method: Regression models
determined engagement in health care IT usage and impact of literacy levels based
on survey data collected from the group. Results: Although most participants have
adequate literacy, they are not more likely to use health care IT than those with
limited literacy scores. Knowledge of how to use the Internet to answer questions
about health was statistically associated with IT usage. Discussion: Health care
IT usage is important for healthy aging. The ability of older adults to
understand information provided to them can impact population health including
medication usage and other important factors.
PMID- 28508023
TI - An unusual presentation of LCAT deficiency as nephrotic syndrome with normal
serum HDL-C level.
AB - Clinical and biochemical manifestations of lecithin-cholesterol acyltransferase
(LCAT) deficiency include an abnormal lipid profile (characterized by
hypercholesterolemia with markedly decreased high-density lipoprotein cholesterol
[HDL-C] and hypertriglyceridemia), corneal opacities, hematologic abnormalities
(normochromic anemia of varying intensity), splenomegaly, variable early coronary
artery disease and nephropathy (initially proteinuria followed by progressive
deterioration of renal function). We presented a patient with nephrotic syndrome,
which renal biopsy revealed classic features of LCAT deficiency. To our
knowledge, the present case is the first reported case of LCAT deficiency
presenting with symptoms related to nephrotic syndrome in a patient with no
obvious family history without any corneal deposits and normal HDL-C levels.
PMID- 28508025
TI - Graphical coding data and operational guidance for implementation or modification
of a LabVIEW(r)-based pHstat system for the cultivation of microalgae.
AB - The influence of pH on phytoplankton physiology is an important facet of the body
of research on ocean acidification. We provide data developed during the design
and implementation of a novel pHstat system capable of maintaining both static
and dynamic pH environments in a laboratory setting. These data both help improve
functionality of the system, and provide specific coding blocks for controlling
the pHstat using a LabVIEW(r) virtual instrument (VI). The data in this paper
support the research article "Development of an economical, autonomous pHstat
system for culturing phytoplankton under steady state or dynamic conditions"
(Golda et al. [2]). These data will be of interest to researchers studying the
effects of changing pH on phytoplankton in a laboratory context, and to those
desiring to build their own pHstat system(s). These data can also be used to
facilitate modification of the pHstat system to control salinity, temperature, or
other environmental factors.
PMID- 28508024
TI - Pilot study of endoscopic retrograde 3-dimensional - computed tomography
enteroclysis for the assessment of Crohn's disease.
AB - PURPOSE: Endoscopic retrograde ileography (ERIG) is developed in our institute
and applied clinically for the diagnosis and assessment of the Crohn's disease
activity. We have further improved the technique using 3-dimensional - computed
tomography enteroclysis (3D-CTE) and conducted a retrospective study to determine
the feasibility and the diagnostic value of endoscopic retrograde 3D-CTE (ER 3D
CTE) in Crohn's disease patients in a state of remission. METHODS: Thirteen
Crohn's patients were included in this pilot study. CTE was performed after the
infusion of air or CO2 through the balloon tube following conventional
colonoscopy. The primary endpoint of this study was to assess the safety of this
method. Secondarily, the specific findings of Crohn's disease and length of the
visualized small intestine were assessed. RESULTS: The procedures were completed
without any adverse events. Gas passed through the small intestine and
enterographic images were obtained in 10 out of 13 cases, but, in the remaining
patients, insertion of the balloon tubes into the terminal ileum failed. Various
features specific to Crohn's disease were visualized using ER 3D-CTE. A cobble
stone appearance or hammock-like malformation was specific and effective for
diagnosing Crohn's disease and the features of anastomosis after the surgical
operations were also well described. Therefore, this technique may be useful
after surgery. CONCLUSION: In this study, ER 3D-CTE was performed safely in
Crohn's disease patients and may be used for the diagnosis and follow-up of this
disease.
PMID- 28508027
TI - Violent actions against children.
AB - We present in this paper a novel dataset (MMU VAAC) for violent actions against
children recognition. This original dataset has been recorded using Microsoft
Kinect with the usage of a child mannequin. MMU VAAC dataset contains skeleton
joints, depth, and RGB modalities.
PMID- 28508026
TI - Fluoride ion adsorption onto palm stone: Optimization through response surface
methodology, isotherm, and adsorbent characteristics data.
AB - In some part of the world, groundwater source can become unsafe for drinking due
to the high concentration of fluoride ions [1]. The low cost and facile-produced
adsorbent like palm stone could effectively removed fluoride ions through
adsorption process. In this dataset, the influence of fluoride ion concentration,
solution pH, adsorbent dosage, and contact time on fluoride ion adsorption by
palm stones was tested by central composite design (CCD) under response surface
methodology (RSM). The data stone carbonized adsorbent was prepared by a simple
and facile method at relatively low temperature of 250 degrees C during 3 h. The
adsorbent had the main functional groups of O-H, -OH, Si-H, C=O, N=O, C-C, C-OR,
C-H, and C-Br on its surface. At the optimized conditions obtained by RSM, about
84.78% of fluoride ion was removed using the adsorbent. The Langmuir isotherm was
suitable for correlation of equilibrium data (maximum adsorption capacity= 3.95
mg/g). Overall, the data offer a facile adsorbent to water and wastewater works
which face to high level of fluoride water/ wastewater content.
PMID- 28508028
TI - Data in support of poisoning related mortalities from southern Himachal Pradesh.
AB - Poisoning has always been pointed as one of the leading causes of human death
throughout the world. Despite the best efforts made by many research institutes,
the worldwide true figure on mortalities with poisoning could never be achieved
due to many reasons. One of the main reasons is the unavailability of complete
database from the rural and catchment areas of the world where these types of
incidents are usual. People can be made aware about this problem by presenting
data articles on regular basis, therefore to mark a resource document these data
should be regularly up-dated. The current data report is a briefing of types and
trends of chemical poisoning amongst human in southern hilly region of Himachal
Pradesh (HP), India. This research database is an outcome of five year
retrospective study based on assessment of records pertaining human deaths
associated with poisoning occurred in southern Himachal Pradesh, and reported at
State Forensic Science Laboratory (SFSL), Junga during 2010-14. Cases where ethyl
alcohol was detected have been put under exclusion criterion. All the cases were
reviewed and summarized in terms of yearly and monthly frequency of reports
wrapping important information portraying the involvement of gender, age,
locality, types of poison, and mode of death in the poisoning incidents. Review
of these scientific reports showed some notable figures having a direct concern
with public and legal domains to promote risk reduction and prevention of
chemical poisonings.
PMID- 28508030
TI - Incidental leiomyosarcoma found at the time of cesarean hysterectomy for morbidly
adherent placenta.
AB - BACKGROUND: Incidental leiomyosarcoma (LMS) is a rare diagnosis in pregnancy or
in the puerperium. To our knowledge, this is the first case reported in the
literature of incidental LMS after cesarean hysterectomy for morbidly adherent
placenta. CASE: We present a case of a cesarean hysterectomy performed for a
suspected morbidly adherent placenta in a patient with three prior cesarean
deliveries, an anterior placenta previa and a fundal fibroid. Subsequent
pathology identified a LMS on final specimen. The patient declined bilateral
oophorectomy and removal of her remaining cervix. No chemotherapy or radiation
was given for her presumed stage IB disease. CONCLUSION: An incidental finding of
a LMS is infrequent; the risk of recurrence is > 50% even if the sarcoma is
removed in its entirety.
PMID- 28508029
TI - A B-Cell Gene Signature Correlates With the Extent of Gluten-Induced Intestinal
Injury in Celiac Disease.
AB - BACKGROUND & AIMS: Celiac disease (CeD) provides an opportunity to study
autoimmunity and the transition in immune cells as dietary gluten induces small
intestinal lesions. METHODS: Seventy-three celiac disease patients on a long
term, gluten-free diet ingested a known amount of gluten daily for 6 weeks. A
peripheral blood sample and intestinal biopsy specimens were taken before and 6
weeks after initiating the gluten challenge. Biopsy results were reported on a
continuous numeric scale that measured the villus-height-to-crypt-depth ratio to
quantify gluten-induced intestinal injury. Pooled B and T cells were isolated
from whole blood, and RNA was analyzed by DNA microarray looking for changes in
peripheral B- and T-cell gene expression that correlated with changes in villus
height to crypt depth, as patients maintained a relatively healthy intestinal
mucosa or deteriorated in the face of a gluten challenge. RESULTS: Gluten
dependent intestinal damage from baseline to 6 weeks varied widely across all
patients, ranging from no change to extensive damage. Genes differentially
expressed in B cells correlated strongly with the extent of intestinal damage. A
relative increase in B-cell gene expression correlated with a lack of sensitivity
to gluten whereas their relative decrease correlated with gluten-induced mucosal
injury. A core B-cell gene module, representing a subset of B-cell genes
analyzed, accounted for the correlation with intestinal injury. CONCLUSIONS:
Genes comprising the core B-cell module showed a net increase in expression from
baseline to 6 weeks in patients with little to no intestinal damage, suggesting
that these individuals may have mounted a B-cell immune response to maintain
mucosal homeostasis and circumvent inflammation. DNA microarray data were
deposited at the GEO repository (accession number: GSE87629; available:
https://www.ncbi.nlm.nih.gov/geo/).
PMID- 28508032
TI - What is the ideal timing for endoscopy in acute upper gastrointestinal bleeding?
PMID- 28508033
TI - Over-the-scope clip (OTSC) reduces surgery rate in the management of iatrogenic
gastrointestinal perforations.
AB - Background and study aims Over-the-scope clip (OTSC) has been recently used in
management of gastrointestinal perforations, but data on it are still limited.
The aim of this study was to compare management of iatrogenic perforations before
and after the OTSC was available in our endoscopy unit. Patients and methods We
conducted a monocentric retrospective study from June 2007 to June 2015. All
iatrogenic gastrointestinal perforations detected during endoscopy were included.
Two time periods were compared in terms of surgery and mortality rates: before
use of OTSC (June 2007 to June 2011) and after OTSC became available (June 2011
to June 2015). Results During the first period, 24 perforations were recorded.
Fifteen (62.5 %) were managed with surgery. The mortality rate was 8 %. During
the second period, 16 perforations occurred. In 11 patients (68.7 %), an OTSC was
used to close the perforation, with complete sealing of the perforation in 100 %
of cases. However, 2 patients with sigmoid perforation had to undergo surgery due
to right ureteral obstruction by the clip in 1 case and to presence of a
localized peritonitis in the other. The surgery rate during this period was 12.5
% (2 /16), with a statistically significant difference compared to the first
period (P = 0.002). There was no mortality in the second period versus 8 % in the
first one (P = 0.23). Conclusions OTSC is effective for endoluminal closure of
iatrogenic perforations and results in a significant decrease in surgery rate.
PMID- 28508031
TI - Altered levels of blood proteins in Alzheimer's disease longitudinal study:
Results from Australian Imaging Biomarkers Lifestyle Study of Ageing cohort.
AB - INTRODUCTION: A blood-based biomarker panel to identify individuals with
preclinical Alzheimer's disease (AD) would be an inexpensive and accessible first
step for routine testing. METHODS: We analyzed 14 biomarkers that have previously
been linked to AD in the Australian Imaging Biomarkers lifestyle longitudinal
study of aging cohort. RESULTS: Levels of apolipoprotein J (apoJ) were higher in
AD individuals compared with healthy controls at baseline and 18 months (P =
.0003) and chemokine-309 (I-309) were increased in AD patients compared to mild
cognitive impaired individuals over 36 months (P = .0008). DISCUSSION: These data
suggest that apoJ may have potential in the context of use (COU) of AD
diagnostics, I-309 may be specifically useful in the COU of identifying
individuals at greatest risk for progressing toward AD. This work takes an
initial step toward identifying blood biomarkers with potential use in the
diagnosis and prognosis of AD and should be validated across other prospective
cohorts.
PMID- 28508034
TI - Laminar Localization and Projection-Specific Properties of Presubicular Neurons
Targeting the Lateral Mammillary Nucleus, Thalamus, or Medial Entorhinal Cortex.
AB - The presubiculum (PrS) is part of an interconnected network of distributed brain
regions where individual neurons signal the animals heading direction. PrS sends
axons to medial entorhinal cortex (MEC), it is reciprocally connected with
anterior thalamic nuclei (ATNs), and it sends feedback projections to the lateral
mammillary nucleus (LMN), involved in generating the head direction signal. The
intrinsic properties of projecting neurons will influence the pathway-specific
transmission of activity. Here, we used projection-specific labeling of
presubicular neurons to identify MEC-, LMN-, and ATN-projecting neurons in mice.
MEC-projecting neurons located in superficial layers II/III were mostly regular
spiking pyramidal neurons, and we also identified a Martinotti-type GABAergic
neuron. The cell bodies of LMN-projecting neurons were located in a well
delimited area in the middle portion of the PrS, which corresponds to layer IV.
The physiology of LMN projecting, pyramidal neurons stood out with a tendency to
fire in bursts of action potentials (APs) with rapid onset. These properties may
be uniquely adapted to reliably transmit visual landmark information with short
latency to upstream LMN. Neurons projecting to ATN were located in layers V/VI,
and they were mostly regular spiking pyramidal neurons. Unsupervised cluster
analysis of intrinsic properties suggested distinct physiological features for
the different categories of projection neurons, with some similarities between
MEC- and ATN-projecting neurons. Projection-specific subpopulations may serve
separate functions in the PrS and may be engaged differently in transmitting head
direction related information.
PMID- 28508037
TI - Arctic greening from warming promotes declines in caribou populations.
AB - The migratory tundra caribou herds in North America follow decadal population
cycles, and browsing from abundant caribou could be expected to counteract the
current climate-driven expansion of shrubs in the circumpolar tundra biome. We
demonstrate that the sea ice cover in the Arctic Ocean has provided a strong
signal for climate-induced changes on the adjacent caribou summer ranges,
outperforming other climate indices in explaining the caribou-plant dynamics. We
found no evidence of a negative effect of caribou abundance on vegetation
biomass. On the contrary, we found a strong bottom-up effect in which a warmer
climate related to diminishing sea ice has increased the plant biomass on the
summer pastures, along with a paradoxical decline in caribou populations. This
result suggests that this climate-induced greening has been accompanied by a
deterioration of pasture quality. The shrub expansion in Arctic North America
involves plant species with strong antibrowsing defenses. Our results might
therefore be an early signal of a climate-driven shift in the caribou-plant
interaction from a system with low plant biomass modulated by cyclic caribou
populations to a system dominated by nonedible shrubs and diminishing herds of
migratory caribou.
PMID- 28508038
TI - Origami by frontal photopolymerization.
AB - Origami structures are of great interest in microelectronics, soft actuators,
mechanical metamaterials, and biomedical devices. Current methods of fabricating
origami structures still have several limitations, such as complex material
systems or tedious processing steps. We present a simple approach for creating
three-dimensional (3D) origami structures by the frontal photopolymerization
method, which can be easily implemented by using a commercial projector. The
concept of our method is based on the volume shrinkage during
photopolymerization. By adding photoabsorbers into the polymer resin, an
attenuated light field is created and leads to a nonuniform curing along the
thickness direction. The layer directly exposed to light cures faster than the
next layer; this nonuniform curing degree leads to nonuniform curing-induced
volume shrinkage. This further introduces a nonuniform stress field, which drives
the film to bend toward the newly formed side. The degree of bending can be
controlled by adjusting the gray scale and the irradiation time, an easy approach
for creating origami structures. The behavior is examined both experimentally and
theoretically. Two methods are also proposed to create different types of 3D
origami structures.
PMID- 28508036
TI - Room temperature stable CO x -free H2 production from methanol with magnesium
oxide nanophotocatalysts.
AB - Methanol, which contains 12.6 weight percent hydrogen, is a good hydrogen storage
medium because it is a liquid at room temperature. However, by releasing the
hydrogen, undesirable CO and/or CO2 byproducts are formed during catalytic fuel
reforming. We show that alkaline earth metal oxides, in our case MgO
nanocrystals, exhibit stable photocatalytic activity for CO/CO2-free H2
production from liquid methanol at room temperature. The performance of MgO
nanocrystals toward methanol dehydrogenation increases with time and approaches
~320 MUmol g-1 hour-1 after a 2-day photocatalytic reaction. The CO x -free H2
production is attributed to methanol photodecomposition to formaldehyde,
photocatalyzed by surface electronic states of unique monodispersed, porous MgO
nanocrystals, which were synthesized with a novel facile colloidal chemical
strategy. An oxygen plasma treatment allows for the removal of organic
surfactants, producing MgO nanocrystals that are well dispersible in methanol.
PMID- 28508035
TI - Flashing Lights Induce Prolonged Distortions in Visual Cortical Responses and
Visual Perception.
AB - The primary sensory neocortex generates an internal representation of the
environment, and its circuit reorganization is thought to lead to a modification
of sensory perception. This reorganization occurs primarily through activity
dependent plasticity and has been well documented in animals during early
developmental stages. Here, we describe a new method for the noninvasive
induction of long-term plasticity in the mature brain: simple transient visual
stimuli (i.e., flashing lights) can be used to induce prolonged modifications in
visual cortical processing and visually driven behaviors. Our previous studies
have shown that, in the primary visual cortex (V1) of mice, a flashing light
stimulus evokes a long-delayed response that persists for seconds. When the mice
were repetitively presented with drifting grating stimuli (conditioned stimuli)
during the flash stimulus-evoked delayed response period, the V1 neurons
exhibited a long-lasting decrease in responsiveness to the conditioned stimuli.
The flash stimulus-induced underrepresentation of the grating motion was specific
to the direction of the conditioned stimuli and was associated with a decrease in
the animal's ability to detect the motion of the drifting gratings. The
neurophysiological and behavioral plasticity both persisted for at least several
hours and required N-methyl-d-aspartate receptor activation in the visual cortex.
We propose that flashing light stimuli can be used as an experimental tool to
investigate the visual function and plasticity of neuronal representations and
perception after a critical period of neocortical plasticity.
PMID- 28508040
TI - Quantum imaging of current flow in graphene.
AB - Since its first discovery in 2004, graphene has been found to host a plethora of
unusual electronic transport phenomena, making it a fascinating system for
fundamental studies in condensed matter physics as well as offering tremendous
opportunities for future electronic and sensing devices. Typically, electronic
transport in graphene has been investigated via resistivity measurements;
however, these measurements are generally blind to spatial information critical
to observing and studying landmark transport phenomena in real space and in
realistic imperfect devices. We apply quantum imaging to the problem and
demonstrate noninvasive, high-resolution imaging of current flow in monolayer
graphene structures. Our method uses an engineered array of near-surface, atomic
sized quantum sensors in diamond to map the vector magnetic field and reconstruct
the vector current density over graphene geometries of varying complexity, from
monoribbons to junctions, with spatial resolution at the diffraction limit and a
projected sensitivity to currents as small as 1 MUA. The measured current maps
reveal strong spatial variations corresponding to physical defects at the
submicrometer scale. The demonstrated method opens up an important new avenue to
investigate fundamental electronic and spin transport in graphene structures and
devices and, more generally, in emerging two-dimensional materials and thin-film
systems.
PMID- 28508039
TI - Naturally acidified habitat selects for ocean acidification-tolerant mussels.
AB - Ocean acidification severely affects bivalves, especially their larval stages.
Consequently, the fate of this ecologically and economically important group
depends on the capacity and rate of evolutionary adaptation to altered ocean
carbonate chemistry. We document successful settlement of wild mussel larvae
(Mytilus edulis) in a periodically CO2-enriched habitat. The larval fitness of
the population originating from the CO2-enriched habitat was compared to the
response of a population from a nonenriched habitat in a common garden
experiment. The high CO2-adapted population showed higher fitness under elevated
Pco2 (partial pressure of CO2) than the non-adapted cohort, demonstrating, for
the first time, an evolutionary response of a natural mussel population to ocean
acidification. To assess the rate of adaptation, we performed a selection
experiment over three generations. CO2 tolerance differed substantially between
the families within the F1 generation, and survival was drastically decreased in
the highest, yet realistic, Pco2 treatment. Selection of CO2-tolerant F1 animals
resulted in higher calcification performance of F2 larvae during early shell
formation but did not improve overall survival. Our results thus reveal
significant short-term selective responses of traits directly affected by ocean
acidification and long-term adaptation potential in a key bivalve species.
Because immediate response to selection did not directly translate into increased
fitness, multigenerational studies need to take into consideration the
multivariate nature of selection acting in natural habitats. Combinations of
short-term selection with long-term adaptation in populations from CO2-enriched
versus nonenriched natural habitats represent promising approaches for estimating
adaptive potential of organisms facing global change.
PMID- 28508042
TI - Toward continuous-wave operation of organic semiconductor lasers.
AB - The demonstration of continuous-wave lasing from organic semiconductor films is
highly desirable for practical applications in the areas of spectroscopy, data
communication, and sensing, but it still remains a challenging objective. We
report low-threshold surface-emitting organic distributed feedback lasers
operating in the quasi-continuous-wave regime at 80 MHz as well as under long
pulse photoexcitation of 30 ms. This outstanding performance was achieved using
an organic semiconductor thin film with high optical gain, high photoluminescence
quantum yield, and no triplet absorption losses at the lasing wavelength combined
with a mixed-order distributed feedback grating to achieve a low lasing
threshold. A simple encapsulation technique greatly reduced the laser-induced
thermal degradation and suppressed the ablation of the gain medium otherwise
taking place under intense continuous-wave photoexcitation. Overall, this study
provides evidence that the development of a continuous-wave organic semiconductor
laser technology is possible via the engineering of the gain medium and the
device architecture.
PMID- 28508044
TI - Data-driven discovery of partial differential equations.
AB - We propose a sparse regression method capable of discovering the governing
partial differential equation(s) of a given system by time series measurements in
the spatial domain. The regression framework relies on sparsity-promoting
techniques to select the nonlinear and partial derivative terms of the governing
equations that most accurately represent the data, bypassing a combinatorially
large search through all possible candidate models. The method balances model
complexity and regression accuracy by selecting a parsimonious model via Pareto
analysis. Time series measurements can be made in an Eulerian framework, where
the sensors are fixed spatially, or in a Lagrangian framework, where the sensors
move with the dynamics. The method is computationally efficient, robust, and
demonstrated to work on a variety of canonical problems spanning a number of
scientific domains including Navier-Stokes, the quantum harmonic oscillator, and
the diffusion equation. Moreover, the method is capable of disambiguating between
potentially nonunique dynamical terms by using multiple time series taken with
different initial data. Thus, for a traveling wave, the method can distinguish
between a linear wave equation and the Korteweg-de Vries equation, for instance.
The method provides a promising new technique for discovering governing equations
and physical laws in parameterized spatiotemporal systems, where first-principles
derivations are intractable.
PMID- 28508041
TI - Mitochondrial protein-linked DNA breaks perturb mitochondrial gene transcription
and trigger free radical-induced DNA damage.
AB - Breakage of one strand of DNA is the most common form of DNA damage. Most damaged
DNA termini require end-processing in preparation for ligation. The importance of
this step is highlighted by the association of defects in the 3'-end processing
enzyme tyrosyl DNA phosphodiesterase 1 (TDP1) and neurodegeneration and by the
cytotoxic induction of protein-linked DNA breaks (PDBs) and oxidized nucleic acid
intermediates during chemotherapy and radiotherapy. Although much is known about
the repair of PDBs in the nucleus, little is known about this process in the
mitochondria. We reveal that TDP1 resolves mitochondrial PDBs (mtPDBs), thereby
promoting mitochondrial gene transcription. Overexpression of a toxic form of
mitochondrial topoisomerase I (TOP1mt*), which generates excessive mtPDBs,
results in a TDP1-dependent compensatory up-regulation of mitochondrial gene
transcription. In the absence of TDP1, the imbalance in transcription of
mitochondrial- and nuclear-encoded electron transport chain (ETC) subunits
results in misassembly of ETC complex III. Bioenergetics profiling further
reveals that TDP1 promotes oxidative phosphorylation under both basal and high
energy demands. It is known that mitochondrial dysfunction results in free
radical leakage and nuclear DNA damage; however, the detection of intermediates
of radical damage to DNA is yet to be shown. Consequently, we report an increased
accumulation of carbon-centered radicals in cells lacking TDP1, using electron
spin resonance spectroscopy. Overexpression of the antioxidant enzyme superoxide
dismutase 1 (SOD1) reduces carbon-centered adducts and protects TDP1-deficient
cells from oxidative stress. Conversely, overexpression of the amyotrophic
lateral sclerosis-associated mutant SOD1G93A leads to marked sensitivity. Whereas
Tdp1 knockout mice develop normally, overexpression of SOD1G93A suggests early
embryonic lethality. Together, our data show that TDP1 resolves mtPDBs, thereby
regulating mitochondrial gene transcription and oxygen consumption by oxidative
phosphorylation, thus conferring cellular protection against reactive oxygen
species-induced damage.
PMID- 28508045
TI - Experimental demonstration of nonbilocal quantum correlations.
AB - Quantum mechanics admits correlations that cannot be explained by local realistic
models. The most studied models are the standard local hidden variable models,
which satisfy the well-known Bell inequalities. To date, most works have focused
on bipartite entangled systems. We consider correlations between three parties
connected via two independent entangled states. We investigate the new type of so
called "bilocal" models, which correspondingly involve two independent hidden
variables. These models describe scenarios that naturally arise in quantum
networks, where several independent entanglement sources are used. Using photonic
qubits, we build such a linear three-node quantum network and demonstrate
nonbilocal correlations by violating a Bell-like inequality tailored for bilocal
models. Furthermore, we show that the demonstration of nonbilocality is more
noise-tolerant than that of standard Bell nonlocality in our three-party quantum
network.
PMID- 28508043
TI - Crystal structure of 2C helicase from enterovirus 71.
AB - Enterovirus 71 (EV71) is the major pathogen responsible for outbreaks of hand,
foot, and mouth disease. EV71 nonstructural protein 2C participates in many
critical events throughout the virus life cycle; however, its precise role is not
fully understood. Lack of a high-resolution structure made it difficult to
elucidate 2C activity and prevented inhibitor development. We report the 2.5 A
resolution crystal structure of the soluble part of EV71 2C, containing an
adenosine triphosphatase (ATPase) domain, a cysteine-rich zinc finger with an
unusual fold, and a carboxyl-terminal helical domain. Unlike other AAA+ ATPases,
EV71 2C undergoes a carboxyl terminus-mediated self-oligomerization, which is
dependent on a specific interaction between the carboxyl-terminal helix of one
monomer and a deep pocket formed between the ATPase and the zinc finger domains
of the neighboring monomer. The carboxyl terminus-mediated self-oligomerization
is fundamental to 2C ATPase activity and EV71 replication. Our findings suggest a
strategy for inhibition of enterovirus replication by disruption of the self
oligomerization interface of 2C.
PMID- 28508046
TI - Carbon-free H2 production from ammonia triggered at room temperature with an
acidic RuO2/gamma-Al2O3 catalyst.
AB - Ammonia has been suggested as a carbon-free hydrogen source, but a convenient
method for producing hydrogen from ammonia with rapid initiation has not been
developed. Ideally, this method would require no external energy input. We
demonstrate hydrogen production by exposing ammonia and O2 at room temperature to
an acidic RuO2/gamma-Al2O3 catalyst. Because adsorption of ammonia onto the
catalyst is exothermic, the catalyst bed is rapidly heated to the catalytic
ammonia autoignition temperature, and subsequent oxidative decomposition of
ammonia produces hydrogen. A differential calorimeter combined with a volumetric
gas adsorption analyzer revealed a large quantity of heat evolved both with
chemisorption of ammonia onto RuO2 and acidic sites on the gamma-Al2O3 and with
physisorption of multiple ammonia molecules.
PMID- 28508047
TI - Kin-based cultural transmission of tool use in wild chimpanzees.
AB - Current research on animal culture has focused strongly on cataloging the
diversity of socially transmitted behaviors and on the social learning mechanisms
that sustain their spread. Comparably less is known about the persistence of
cultural behavior following innovation in groups of wild animals. We present
observational data and a field experiment designed to address this question in a
wild chimpanzee community, capitalizing on a novel tool behavior, moss-sponging,
which appeared naturally in the community in 2011. We found that, 3 years later,
moss-sponging was still present in the individuals that acquired the behavior
shortly after its emergence and that it had spread further, to other community
members. Our field experiment suggests that this secondary radiation and
consolidation of moss-sponging is the result of transmission through matrilines,
in contrast to the previously documented association-based spread among the
initial cohort. We conclude that the spread of cultural behavior in wild
chimpanzees follows a sequential structure of initial proximity-based horizontal
transmission followed by kin-based vertical transmission.
PMID- 28508048
TI - Optical identification of sulfur vacancies: Bound excitons at the edges of
monolayer tungsten disulfide.
AB - Defects play a significant role in tailoring the optical properties of two
dimensional materials. Optical signatures of defect-bound excitons are important
tools to probe defective regions and thus interrogate the optical quality of as
grown semiconducting monolayer materials. We have performed a systematic study of
defect-bound excitons using photoluminescence (PL) spectroscopy combined with
atomically resolved scanning electron microscopy and first-principles
calculations. Spatially resolved PL spectroscopy at low temperatures revealed
bound excitons that were present only on the edges of monolayer tungsten
disulfide and not in the interior. Optical pumping of the bound excitons was
sublinear, confirming their bound nature. Atomic-resolution images reveal that
the areal density of monosulfur vacancies is much larger near the edges (0.92 +/-
0.45 nm-2) than in the interior (0.33 +/- 0.11 nm-2). Temperature-dependent PL
measurements found a thermal activation energy of ~36 meV; surprisingly, this is
much smaller than the bound-exciton binding energy of ~300 meV. We show that this
apparent inconsistency is related to a thermal dissociation of the bound exciton
that liberates the neutral excitons from negatively charged point defects. First
principles calculations confirm that sulfur monovacancies introduce midgap states
that host optical transitions with finite matrix elements, with emission energies
ranging from 200 to 400 meV below the neutral-exciton emission line. These
results demonstrate that bound-exciton emission induced by monosulfur vacancies
is concentrated near the edges of as-grown monolayer tungsten disulfide.
PMID- 28508049
TI - Mechanism and color modulation of fungal bioluminescence.
AB - Bioluminescent fungi are spread throughout the globe, but details on their
mechanism of light emission are still scarce. Usually, the process involves three
key components: an oxidizable luciferin substrate, a luciferase enzyme, and a
light emitter, typically oxidized luciferin, and called oxyluciferin. We report
the structure of fungal oxyluciferin, investigate the mechanism of fungal
bioluminescence, and describe the use of simple synthetic alpha-pyrones as
luciferins to produce multicolor enzymatic chemiluminescence. A high-energy
endoperoxide is proposed as an intermediate of the oxidation of the native
luciferin to the oxyluciferin, which is a pyruvic acid adduct of caffeic acid.
Luciferase promiscuity allows the use of simple alpha-pyrones as chemiluminescent
substrates.
PMID- 28508052
TI - Miocene flooding events of western Amazonia.
AB - There is a considerable controversy about whether western Amazonia was ever
covered by marine waters during the Miocene [23 to 5 Ma (million years ago)]. We
investigated the possible occurrence of Miocene marine incursions in the Llanos
and Amazonas/Solimoes basins, using sedimentological and palynological data from
two sediment cores taken in eastern Colombia and northwestern Brazil together
with seismic information. We observed two distinct marine intervals in the Llanos
Basin, an early Miocene that lasted ~0.9 My (million years) (18.1 to 17.2 Ma) and
a middle Miocene that lasted ~3.7 My (16.1 to 12.4 Ma). These two marine
intervals are also seen in Amazonas/Solimoes Basin (northwestern Amazonia) but
were much shorter in duration, ~0.2 My (18.0 to 17.8 Ma) and ~0.4 My (14.1 to
13.7 Ma), respectively. Our results indicate that shallow marine waters covered
the region at least twice during the Miocene, but the events were short-lived,
rather than a continuous full-marine occupancy of Amazonian landscape over
millions of years.
PMID- 28508050
TI - Butterfly gyroid nanostructures as a time-frozen glimpse of intracellular
membrane development.
AB - The formation of the biophotonic gyroid material in butterfly wing scales is an
exceptional feat of evolutionary engineering of functional nanostructures. It is
hypothesized that this nanostructure forms by chitin polymerization inside a
convoluted membrane of corresponding shape in the endoplasmic reticulum. However,
this dynamic formation process, including whether membrane folding and chitin
expression are simultaneous or sequential processes, cannot yet be elucidated by
in vivo imaging. We report an unusual hierarchical ultrastructure in the
butterfly Thecla opisena that, as a solid material, allows high-resolution three
dimensional microscopy. Rather than the conventional polycrystalline space
filling arrangement, a gyroid occurs in isolated facetted crystallites with a
pronounced size gradient. When interpreted as a sequence of time-frozen snapshots
of the morphogenesis, this arrangement provides insight into the formation
mechanisms of the nanoporous gyroid material as well as of the intracellular
organelle membrane that acts as the template.
PMID- 28508053
TI - Backside absorbing layer microscopy: Watching graphene chemistry.
AB - The rapid rise of two-dimensional nanomaterials implies the development of new
versatile, high-resolution visualization and placement techniques. For example, a
single graphene layer becomes observable on Si/SiO2 substrates by reflected light
under optical microscopy because of interference effects when the thickness of
silicon oxide is optimized. However, differentiating monolayers from bilayers
remains challenging, and advanced techniques, such as Raman mapping, atomic force
microscopy (AFM), or scanning electron microscopy (SEM) are more suitable to
observe graphene monolayers. The first two techniques are slow, and the third is
operated in vacuum; hence, in all cases, real-time experiments including notably
chemical modifications are not accessible. The development of optical microscopy
techniques that combine the speed, large area, and high contrast of SEM with the
topological information of AFM is therefore highly desirable. We introduce a new
widefield optical microscopy technique based on the use of previously unknown
antireflection and absorbing (ARA) layers that yield ultrahigh contrast
reflection imaging of monolayers. The BALM (backside absorbing layer microscopy)
technique can achieve the subnanometer-scale vertical resolution, large area, and
real-time imaging. Moreover, the inverted optical microscope geometry allows its
easy implementation and combination with other techniques. We notably demonstrate
the potentiality of BALM by in operando imaging chemical modifications of
graphene oxide. The technique can be applied to the deposition, observation, and
modification of any nanometer-thick materials.
PMID- 28508051
TI - Genuine binding energy of the hydrated electron.
AB - The unknown influence of inelastic and elastic scattering of slow electrons in
water has made it difficult to clarify the role of the solvated electron in
radiation chemistry and biology. We combine accurate scattering simulations with
experimental photoemission spectroscopy of the hydrated electron in a liquid
water microjet, with the aim of resolving ambiguities regarding the influence of
electron scattering on binding energy spectra, photoelectron angular
distributions, and probing depths. The scattering parameters used in the
simulations are retrieved from independent photoemission experiments of water
droplets. For the ground-state hydrated electron, we report genuine values devoid
of scattering contributions for the vertical binding energy and the anisotropy
parameter of 3.7 +/- 0.1 eV and 0.6 +/- 0.2, respectively. Our probing depths
suggest that even vacuum ultraviolet probing is not particularly surface
selective. Our work demonstrates the importance of quantitative scattering
simulations for a detailed analysis of key properties of the hydrated electron.
PMID- 28508054
TI - Flexible adaptation of male germ cells from female iPSCs of endangered Tokudaia
osimensis.
AB - In mammals, the Y chromosome strictly influences the maintenance of male germ
cells. Almost all mammalian species require genetic contributors to generate
testes. An endangered species, Tokudaia osimensis, has a unique sex chromosome
composition XO/XO, and genetic differences between males and females have not
been confirmed. Although a distinctive sex-determining mechanism may exist in T.
osimensis, it has been difficult to examine thoroughly in this rare animal
species. To elucidate the discriminative sex-determining mechanism in T.
osimensis and to find a strategy to prevent its possible extinction, we have
established induced pluripotent stem cells (iPSCs) and derived interspecific
chimeras using mice as the hosts and recipients. Generated iPSCs are considered
to be in the so-called "true naive" state, and T. osimensis iPSCs may contribute
as interspecific chimeras to several different tissues and cells in live animals.
Surprisingly, female T. osimensis iPSCs not only contributed to the female germ
line in the interspecific mouse ovary but also differentiated into spermatocytes
and spermatids that survived in the adult interspecific mouse testes. Thus, T.
osimensis cells have high sexual plasticity through which female somatic cells
can be converted to male germline cells. These findings suggest flexibility in T.
osimensis cells, which can adapt their germ cell sex to the gonadal niche. The
probable reduction of the extinction risk of an endangered species through the
use of iPSCs is indicated by this study.
PMID- 28508056
TI - Picosecond amorphization of SiO2 stishovite under tension.
AB - It is extremely difficult to realize two conflicting properties-high hardness and
toughness-in one material. Nano-polycrystalline stishovite, recently synthesized
from Earth-abundant silica glass, proved to be a super-hard, ultra-tough
material, which could provide sustainable supply of high-performance ceramics.
Our quantum molecular dynamics simulations show that stishovite amorphizes
rapidly on the order of picosecond under tension in front of a crack tip. We find
a displacive amorphization mechanism that only involves short-distance collective
motions of atoms, thereby facilitating the rapid transformation. The two-step
amorphization pathway involves an intermediate state akin to experimentally
suggested "high-density glass polymorphs" before eventually transforming to
normal glass. The rapid amorphization can catch up with, screen, and self-heal a
fast-moving crack. This new concept of fast amorphization toughening likely
operates in other pressure-synthesized hard solids.
PMID- 28508057
TI - Low-energy structural dynamics of ferroelectric domain walls in hexagonal rare
earth manganites.
AB - Domain walls (DWs) in ferroic materials, across which the order parameter
abruptly changes its orientation, can host emergent properties that are absent in
the bulk domains. Using a broadband (106 to 1010 Hz) scanning impedance
microscope, we show that the electrical response of the interlocked antiphase
boundaries and ferroelectric DWs in hexagonal rare-earth manganites (h-RMnO3) is
dominated by the bound-charge oscillation rather than free-carrier conduction at
the DWs. As a measure of the rate of energy dissipation, the effective
conductivity of DWs on the (001) surfaces of h-RMnO3 at gigahertz frequencies is
drastically higher than that at dc, whereas the effect is absent on surfaces with
in-plane polarized domains. First-principles and model calculations indicate that
the frequency range and selection rules are consistent with the periodic sliding
of the DW around its equilibrium position. This acoustic wave-like mode, which is
associated with the synchronized oscillation of local polarization and apical
oxygen atoms, is localized perpendicular to the DW but free to propagate along
the DW plane. Our results break the ground to understand structural DW dynamics
and exploit new interfacial phenomena for novel devices.
PMID- 28508058
TI - New technology reveals the role of giant larvaceans in oceanic carbon cycling.
AB - To accurately assess the impacts of climate change on our planet, modeling of
oceanic systems and understanding how atmospheric carbon is transported from
surface waters to the deep benthos are required. The biological pump drives the
transport of carbon through the ocean's depths, and the rates at which carbon is
removed and sequestered are often dependent on the grazing abilities of surface
and midwater organisms. Some of the most effective and abundant midwater grazers
are filter-feeding invertebrates. Although the impact of smaller, near-surface
filter feeders is generally known, efforts to quantify the impact of deeper
filter feeders, such as giant larvaceans, have been unsuccessful. Giant
larvaceans occupy the upper 400 m of the water column, where they build complex
mucus filtering structures that reach diameters greater than 1 m. Because of the
fragility of these structures, direct measurements of filtration rates require in
situ methods. Hence, we developed DeepPIV, an instrument deployed from a remotely
operated vehicle that enables the direct measurement of in situ filtration rates.
The rates measured for giant larvaceans exceed those of any other zooplankton
filter feeder. Given these filtration rates and abundance data from a 22-year
time series, the grazing impact of giant larvaceans far exceeds previous
estimates, with the potential for processing their 200-m principal depth range in
Monterey Bay in as little as 13 days. Technologies such as DeepPIV will enable
more accurate assessments of the long-term removal of atmospheric carbon by deep
water biota.
PMID- 28508055
TI - Antiarrhythmics cure brain arrhythmia: The imperativeness of subthalamic ERG K+
channels in parkinsonian discharges.
AB - ERG K+ channels have long been known to play a crucial role in shaping cardiac
action potentials and, thus, appropriate heart rhythms. The functional role of
ERG channels in the central nervous system, however, remains elusive. We
demonstrated that ERG channels exist in subthalamic neurons and have similar
gating characteristics to those in the heart. ERG channels contribute crucially
not only to the setting of membrane potential and, consequently, the firing
modes, but also to the configuration of burst discharges and, consequently, the
firing frequency and automaticity of the subthalamic neurons. Moreover,
modulation of subthalamic discharges via ERG channels effectively modulates
locomotor behaviors. ERG channel inhibitors ameliorate parkinsonian symptoms,
whereas enhancers render normal animals hypokinetic. Thus, ERG K+ channels could
be vital to the regulation of both cardiac and neuronal rhythms and may
constitute an important pathophysiological basis and pharmacotherapeutic target
for the growing list of neurological disorders related to "brain arrhythmias."
PMID- 28508059
TI - Experimental evidence of hourglass fermion in the candidate nonsymmorphic
topological insulator KHgSb.
AB - Topological insulators (TIs) host novel states of quantum matter characterized by
nontrivial conducting boundary states connecting valence and conduction bulk
bands. All TIs discovered experimentally so far rely on either time-reversal or
mirror crystal symmorphic symmetry to protect massless Dirac-like boundary
states. Several materials were recently proposed to be TIs with nonsymmorphic
symmetry, where a glide mirror protects exotic surface fermions with hourglass
shaped dispersion. However, an experimental confirmation of this new fermion is
missing. Using angle-resolved photoemission spectroscopy, we provide experimental
evidence of hourglass fermions on the (010) surface of crystalline KHgSb, whereas
the (001) surface has no boundary state, in agreement with first-principles
calculations. Our study will stimulate further research activities of topological
properties of nonsymmorphic materials.
PMID- 28508061
TI - Electroplating lithium transition metal oxides.
AB - Materials synthesis often provides opportunities for innovation. We demonstrate a
general low-temperature (260 degrees C) molten salt electrodeposition approach to
directly electroplate the important lithium-ion (Li-ion) battery cathode
materials LiCoO2, LiMn2O4, and Al-doped LiCoO2. The crystallinities and
electrochemical capacities of the electroplated oxides are comparable to those of
the powders synthesized at much higher temperatures (700 degrees to 1000 degrees
C). This new growth method significantly broadens the scope of battery form
factors and functionalities, enabling a variety of highly desirable battery
properties, including high energy, high power, and unprecedented electrode
flexibility.
PMID- 28508060
TI - In vivo mapping of tissue- and subcellular-specific proteomes in Caenorhabditis
elegans.
AB - Multicellular organisms are composed of tissues that have distinct functions
requiring specialized proteomes. To define the proteome of a live animal with
tissue and subcellular resolution, we adapted a localized proteomics technology
for use in the multicellular model organism Caenorhabditis elegans. This approach
couples tissue- and location-specific expression of the enzyme ascorbate
peroxidase (APX), which enables proximity-based protein labeling in vivo, and
quantitative proteomics to identify tissue- and subcellular-restricted proteomes.
We identified and localized more than 3000 proteins from strains of C. elegans
expressing APX in either the nucleus or cytoplasm of the intestine, epidermis,
body wall muscle, or pharyngeal muscle. We also identified several hundred
proteins that were specifically localized to one of the four tissues analyzed or
specifically localized to the cytoplasm or the nucleus. This approach resulted in
the identification both of proteins with previously characterized localizations
and of those not known to localize to the nucleus or cytoplasm. Further, we
confirmed the tissue- and subcellular-specific localization of a subset of
identified proteins using green fluorescent protein tagging and fluorescence
microscopy, validating our in vivo proximity-based proteomics technique.
Together, these results demonstrate a new approach that enables the tissue- and
subcellular-specific identification and quantification of proteins within a live
animal.
PMID- 28508062
TI - Resonant laser printing of structural colors on high-index dielectric
metasurfaces.
AB - Man-made structural colors, which originate from resonant interactions between
visible light and manufactured nanostructures, are emerging as a solution for ink
free color printing. We show that non-iridescent structural colors can be
conveniently produced by nanostructures made from high-index dielectric
materials. Compared to plasmonic analogs, color surfaces with high-index
dielectrics, such as germanium (Ge), have a lower reflectance, yielding a
superior color contrast. Taking advantage of band-to-band absorption in Ge, we
laser-postprocess Ge color metasurfaces with morphology-dependent resonances.
Strong on-resonance energy absorption under pulsed laser irradiation locally
elevates the lattice temperature (exceeding 1200 K) in an ultrashort time scale
(1 ns). This forms the basis for resonant laser printing, where rapid melting
allows for surface energy-driven morphology changes with associated modification
of color appearance. Laser-printable high-index dielectric color metasurfaces are
scalable to a large area and open a new paradigm for printing and decoration with
nonfading and vibrant colors.
PMID- 28508065
TI - The ground truth about metadata and community detection in networks.
AB - Across many scientific domains, there is a common need to automatically extract a
simplified view or coarse-graining of how a complex system's components interact.
This general task is called community detection in networks and is analogous to
searching for clusters in independent vector data. It is common to evaluate the
performance of community detection algorithms by their ability to find so-called
ground truth communities. This works well in synthetic networks with planted
communities because these networks' links are formed explicitly based on those
known communities. However, there are no planted communities in real-world
networks. Instead, it is standard practice to treat some observed discrete-valued
node attributes, or metadata, as ground truth. We show that metadata are not the
same as ground truth and that treating them as such induces severe theoretical
and practical problems. We prove that no algorithm can uniquely solve community
detection, and we prove a general No Free Lunch theorem for community detection,
which implies that there can be no algorithm that is optimal for all possible
community detection tasks. However, community detection remains a powerful tool
and node metadata still have value, so a careful exploration of their
relationship with network structure can yield insights of genuine worth. We
illustrate this point by introducing two statistical techniques that can quantify
the relationship between metadata and community structure for a broad class of
models. We demonstrate these techniques using both synthetic and real-world
networks, and for multiple types of metadata and community structures.
PMID- 28508063
TI - The long noncoding RNA SPRIGHTLY acts as an intranuclear organizing hub for pre
mRNA molecules.
AB - Molecular mechanisms by which long noncoding RNA (lncRNA) molecules may influence
cancerous condition are poorly understood. The aberrant expression of SPRIGHTLY
lncRNA, encoded within the drosophila gene homolog Sprouty-4 intron, is
correlated with a variety of cancers, including human melanomas. We demonstrate
by SHAPE-seq and dChIRP that SPRIGHTLY RNA secondary structure has a core
pseudoknotted domain. This lncRNA interacts with the intronic regions of six pre
mRNAs: SOX5, SMYD3, SND1, MEOX2, DCTN6, and RASAL2, all of which have cancer
related functions. Hemizygous knockout of SPRIGHTLY by CRISPR (clustered
regularly interspaced short palindromic repeats)/Cas9 in melanoma cells
significantly decreases SPRIGHTLY lncRNA levels, simultaneously decreases the
levels of its interacting pre-mRNA molecules, and decreases anchorage-independent
growth rate of cells and the rate of in vivo tumor growth in mouse xenografts.
These results provide the first demonstration of an lncRNA's three-dimensional
coordinating role in facilitating cancer-related gene expression in human
melanomas.
PMID- 28508066
TI - Australian shelf sediments reveal shifts in Miocene Southern Hemisphere
westerlies.
AB - Global climate underwent a major reorganization when the Antarctic ice sheet
expanded ~14 million years ago (Ma) (1). This event affected global atmospheric
circulation, including the strength and position of the westerlies and the
Intertropical Convergence Zone (ITCZ), and, therefore, precipitation patterns (2
5). We present new shallow-marine sediment records from the continental shelf of
Australia (International Ocean Discovery Program Sites U1459 and U1464) providing
the first empirical evidence linking high-latitude cooling around Antarctica to
climate change in the (sub)tropics during the Miocene. We show that Western
Australia was arid during most of the Middle Miocene. Southwest Australia became
wetter during the Late Miocene, creating a climate gradient with the arid
interior, whereas northwest Australia remained arid throughout. Precipitation and
river runoff in southwest Australia gradually increased from 12 to 8 Ma, which we
relate to a northward migration or intensification of the westerlies possibly due
to increased sea ice in the Southern Ocean (5). Abrupt aridification indicates
that the westerlies shifted back to a position south of Australia after 8 Ma. Our
midlatitude Southern Hemisphere data are consistent with the inference that
expansion of sea ice around Antarctica resulted in a northward movement of the
westerlies. In turn, this may have pushed tropical atmospheric circulation and
the ITCZ northward, shifting the main precipitation belt over large parts of
Southeast Asia (4).
PMID- 28508064
TI - Fibulin-4 is essential for maintaining arterial wall integrity in conduit but not
muscular arteries.
AB - Homozygous or compound heterozygous mutations in fibulin-4 (FBLN4) lead to
autosomal recessive cutis laxa type 1B (ARCL1B), a multisystem disorder
characterized by significant cardiovascular abnormalities, including abnormal
elastin assembly, arterial tortuosity, and aortic aneurysms. We sought to
determine the consequences of a human disease-causing mutation in FBLN4 (E57K) on
the cardiovascular system and vascular elastic fibers in a mouse model of ARCL1B.
Fbln4E57K/E57K mice were hypertensive and developed arterial elongation,
tortuosity, and ascending aortic aneurysms. Smooth muscle cell organization
within the arterial wall of large conducting vessels was abnormal, and elastic
fibers were fragmented and had a moth-eaten appearance. In contrast, vessel wall
structure and elastic fiber integrity were normal in resistance/muscular arteries
(renal, mesenteric, and saphenous). Elastin cross-linking and total elastin
content were unchanged in large or small arteries, whereas elastic fiber
architecture was abnormal in large vessels. While the E57K mutation did not
affect Fbln4 mRNA levels, FBLN4 protein was lower in the ascending aorta of
mutant animals compared to wild-type arteries but equivalent in mesenteric
arteries. We found a differential role of FBLN4 in elastic fiber assembly, where
it functions mainly in large conduit arteries. These results suggest that elastin
assembly has different requirements depending on vessel type. Normal levels of
elastin cross-links in mutant tissue call into question FBLN4's suggested role in
mediating lysyl oxidase-elastin interactions. Future studies investigating tissue
specific elastic fiber assembly may lead to novel therapeutic interventions for
ARCL1B and other disorders of elastic fiber assembly.
PMID- 28508068
TI - Emergence of topological semimetals in gap closing in semiconductors without
inversion symmetry.
AB - A band gap for electronic states in crystals governs various properties of
solids, such as transport, optical, and magnetic properties. Its estimation and
control have been an important issue in solid-state physics. The band gap can be
controlled externally by various parameters, such as pressure, atomic
compositions, and external field. Sometimes, the gap even collapses by tuning
some parameter. In the field of topological insulators, this closing of the gap
at a time-reversal invariant momentum indicates a band inversion, that is, it
leads to a topological phase transition from a normal insulator to a topological
insulator. We show, through an exhaustive study on possible space groups, that
the gap closing in inversion-asymmetric crystals is universal, in the sense that
the gap closing always leads either to a Weyl semimetal or to a nodal-line
semimetal. We consider three-dimensional spinful systems with time-reversal
symmetry. The space group of the system and the wave vector at the gap closing
uniquely determine which possibility occurs and where the gap-closing points or
lines lie in the wave vector space after the closing of the gap. In particular,
we show that an insulator-to-insulator transition never happens, which is in
sharp contrast to inversion-symmetric systems.
PMID- 28508067
TI - Cryo-EM structure of human adenovirus D26 reveals the conservation of structural
organization among human adenoviruses.
AB - Human adenoviruses (HAdVs) cause acute respiratory, ocular, and gastroenteric
diseases and are also frequently used as gene and vaccine delivery vectors.
Unlike the archetype human adenovirus C5 (HAdV-C5), human adenovirus D26 (HAdV
D26) belongs to species-D HAdVs, which target different cellular receptors, and
is differentially recognized by immune surveillance mechanisms. HAdV-D26 is being
championed as a lower seroprevalent vaccine and oncolytic vector in preclinical
and human clinical studies. To understand the molecular basis for their distinct
biological properties and independently validate the structures of minor
proteins, we determined the first structure of species-D HAdV at 3.7 A resolution
by cryo-electron microscopy. All the hexon hypervariable regions (HVRs),
including HVR1, have been identified and exhibit a distinct organization compared
to those of HAdV-C5. Despite the differences in the arrangement of helices in the
coiled-coil structures, protein IX molecules form a continuous hexagonal network
on the capsid exterior. In addition to the structurally conserved region (3 to
300) of IIIa, we identified an extra helical domain comprising residues 314 to
390 that further stabilizes the vertex region. Multiple (two to three) copies of
the cleaved amino-terminal fragment of protein VI (pVIn) are observed in each
hexon cavity, suggesting that there could be >=480 copies of VI present in HAdV
D26. In addition, a localized asymmetric reconstruction of the vertex region
provides new details of the three-pronged "claw hold" of the trimeric fiber and
its interactions with the penton base. These observations resolve the previous
conflicting assignments of the minor proteins and suggest the likely conservation
of their organization across different HAdVs.
PMID- 28508069
TI - High-predation habitats affect the social dynamics of collective exploration in a
shoaling fish.
AB - Collective decisions play a major role in the benefits that animals gain from
living in groups. Although the mechanisms of how groups collectively make
decisions have been extensively researched, the response of within-group dynamics
to ecological conditions is virtually unknown, despite adaptation to the
environment being a cornerstone in biology. We investigate how within-group
interactions during exploration of a novel environment are shaped by predation, a
major influence on the behavior of prey species. We tested guppies (Poecilia
reticulata) from rivers varying in predation risk under controlled laboratory
conditions and find the first evidence of differences in group interactions
between animals adapted to different levels of predation. Fish from high
predation habitats showed the strongest negative relationship between initiating
movements and following others, which resulted in less variability in the total
number of movements made between individuals. This relationship between
initiating movements and following others was associated with differentiation
into initiators and followers, which was only observed in fish from high
predation rivers. The differentiation occurred rapidly, as trials lasted 5 min,
and was related to shoal cohesion, where more diverse groups from high-predation
habitats were more cohesive. Our results show that even within a single species
over a small geographical range, decision-making in a social context can vary
with local ecological factors.
PMID- 28508071
TI - Self-assembled micro-organogels for 3D printing silicone structures.
AB - The widespread prevalence of commercial products made from microgels illustrates
the immense practical value of harnessing the jamming transition; there are
countless ways to use soft, solid materials that fluidize and become solid again
with small variations in applied stress. The traditional routes of microgel
synthesis produce materials that predominantly swell in aqueous solvents or, less
often, in aggressive organic solvents, constraining ways that these exceptionally
useful materials can be used. For example, aqueous microgels have been used as
the foundation of three-dimensional (3D) bioprinting applications, yet the
incompatibility of available microgels with nonpolar liquids, such as oils,
limits their use in 3D printing with oil-based materials, such as silicone. We
present a method to make micro-organogels swollen in mineral oil, using block
copolymer self-assembly. The rheological properties of this micro-organogel
material can be tuned, leveraging the jamming transition to facilitate its use in
3D printing of silicone structures. We find that the minimum printed feature size
can be controlled by the yield stress of the micro-organogel medium, enabling the
fabrication of numerous complex silicone structures, including branched
perfusable networks and functional fluid pumps.
PMID- 28508070
TI - Decoupling of microbial carbon, nitrogen, and phosphorus cycling in response to
extreme temperature events.
AB - Predicted changes in the intensity and frequency of climate extremes urge a
better mechanistic understanding of the stress response of microbially mediated
carbon (C) and nutrient cycling processes. We analyzed the resistance and
resilience of microbial C, nitrogen (N), and phosphorus (P) cycling processes and
microbial community composition in decomposing plant litter to transient, but
severe, temperature disturbances, namely, freeze-thaw and heat. Disturbances led
temporarily to a more rapid cycling of C and N but caused a down-regulation of P
cycling. In contrast to the fast recovery of the initially stimulated C and N
processes, we found a slow recovery of P mineralization rates, which was not
accompanied by significant changes in community composition. The functional and
structural responses to the two distinct temperature disturbances were markedly
similar, suggesting that direct negative physical effects and costs associated
with the stress response were comparable. Moreover, the stress response of
extracellular enzyme activities, but not that of intracellular microbial
processes (for example, respiration or N mineralization), was dependent on the
nutrient content of the resource through its effect on microbial physiology and
community composition. Our laboratory study provides novel insights into the
mechanisms of microbial functional stress responses that can serve as a basis for
field studies and, in particular, illustrates the need for a closer integration
of microbial C-N-P interactions into climate extremes research.
PMID- 28508072
TI - Dramatic influence of curvature of nanowire on chiral domain wall velocity.
AB - The use of current pulses to move domain walls along nanowires is one of the most
exciting developments in spintronics over the past decade. We show that changing
the sign of the curvature of a nanowire changes the speed of chiral Neel domain
walls in perpendicularly magnetized nanowires by up to a factor of 10. The domain
walls have an increased or decreased velocity in wires of a given curvature,
independent of the domain wall chirality and the sign of the current-induced spin
orbit torques. Thus, adjacent domain walls move at different speeds. For steady
motion of domain walls along the curved nanowire, the torque must increase
linearly with the radius, which thereby results in a width-dependent tilting of
the domain wall. We show that by using synthetic antiferromagnetic nanowires, the
influence of the curvature on the domain wall's velocity is eliminated, and all
domain walls move together, emphasizing the use of such structures for spintronic
applications.
PMID- 28508073
TI - Three-dimensional system enabling the maintenance and directed differentiation of
pluripotent stem cells under defined conditions.
AB - The development of in vitro models for the maintenance and differentiation of
pluripotent stem cells (PSCs) is an active area of stem cell research. The
strategies used so far are based mainly on two-dimensional (2D) cultures, in
which cellular phenotypes are regulated by soluble factors. We show that a 3D
culture system with atelocollagen porous scaffolds can significantly improve the
outcome of the current platforms intended for the maintenance and lineage
specification of mouse PSCs (mPSCs). Unlike 2D conditions, the 3D conditions
maintained the undifferentiated state of mouse embryonic stem cells (mESCs)
without exogenous stimulation and also supported endoderm, mesoderm, and ectoderm
differentiation of mESCs under serum-free conditions. Moreover, 3D mPSC-derived
mesodermal cells showed accelerated osteogenic differentiation, giving rise to
functional osteoblast-osteocyte populations within calcified structures. The
present strategy offers a 3D platform suitable for the formation of organoids
that mimic in vivo organs containing various cell types, and it may be adaptable
to the generation of ectoderm-, mesoderm-, and endoderm-derived tissues when
combined with appropriate differentiation treatments.
PMID- 28508074
TI - Pressure compression of CdSe nanoparticles into luminescent nanowires.
AB - Oriented attachment (OA) of synthetic nanocrystals is emerging as an effective
means of fabricating low-dimensional nanoscale materials. However, OA relies on
energetically favorable nanocrystal facets to grow nanostructured materials.
Consequently, nanostructures synthesized through OA are generally limited to a
specific crystal facet in their final morphology. We report our discovery that
high-pressure compression can induce consolidation of spherical CdSe nanocrystal
arrays, leading to unexpected one-dimensional semiconductor nanowires that do not
exhibit the typical crystal facet. In particular, in situ high-pressure
synchrotron x-ray scattering, optical spectroscopy, and high-resolution
transmission electron microscopy characterizations indicate that by manipulating
the coupling between nanocrystals through external pressure, a reversible change
in nanocrystal assemblies and properties can be achieved at modest pressure. When
pressure is increased above a threshold, these nanocrystals begin to contact one
another and consolidate, irreversibly forming one-dimensional luminescent
nanowires. High-fidelity molecular dynamics (MD) methods were used to calculate
surface energies and simulate compression and coalescence mechanisms of CdSe
nanocrystals. The MD results provide new insight into nanowire assembly dynamics
and phase stability of nanocrystalline structures.
PMID- 28508076
TI - Machine learning of accurate energy-conserving molecular force fields.
AB - Using conservation of energy-a fundamental property of closed classical and
quantum mechanical systems-we develop an efficient gradient-domain machine
learning (GDML) approach to construct accurate molecular force fields using a
restricted number of samples from ab initio molecular dynamics (AIMD)
trajectories. The GDML implementation is able to reproduce global potential
energy surfaces of intermediate-sized molecules with an accuracy of 0.3 kcal mol
1 for energies and 1 kcal mol-1 A-1 for atomic forces using only 1000
conformational geometries for training. We demonstrate this accuracy for AIMD
trajectories of molecules, including benzene, toluene, naphthalene, ethanol,
uracil, and aspirin. The challenge of constructing conservative force fields is
accomplished in our work by learning in a Hilbert space of vector-valued
functions that obey the law of energy conservation. The GDML approach enables
quantitative molecular dynamics simulations for molecules at a fraction of cost
of explicit AIMD calculations, thereby allowing the construction of efficient
force fields with the accuracy and transferability of high-level ab initio
methods.
PMID- 28508075
TI - Fast iodide-SAD phasing for high-throughput membrane protein structure
determination.
AB - We describe a fast, easy, and potentially universal method for the de novo
solution of the crystal structures of membrane proteins via iodide-single
wavelength anomalous diffraction (I-SAD). The potential universality of the
method is based on a common feature of membrane proteins-the availability at the
hydrophobic-hydrophilic interface of positively charged amino acid residues with
which iodide strongly interacts. We demonstrate the solution using I-SAD of four
crystal structures representing different classes of membrane proteins, including
a human G protein-coupled receptor (GPCR), and we show that I-SAD can be applied
using data collection strategies based on either standard or serial x-ray
crystallography techniques.
PMID- 28508077
TI - Resilience offers escape from trapped thinking on poverty alleviation.
AB - The poverty trap concept strongly influences current research and policy on
poverty alleviation. Financial or technological inputs intended to "push" the
rural poor out of a poverty trap have had many successes but have also failed
unexpectedly with serious ecological and social consequences that can reinforce
poverty. Resilience thinking can help to (i) understand how these failures emerge
from the complex relationships between humans and the ecosystems on which they
depend and (ii) navigate diverse poverty alleviation strategies, such as
transformative change, that may instead be required. First, we review commonly
observed or assumed social-ecological relationships in rural development
contexts, focusing on economic, biophysical, and cultural aspects of poverty.
Second, we develop a classification of poverty alleviation strategies using
insights from resilience research on social-ecological change. Last, we use these
advances to develop stylized, multidimensional poverty trap models. The models
show that (i) interventions that ignore nature and culture can reinforce poverty
(particularly in agrobiodiverse landscapes), (ii) transformative change can
instead open new pathways for poverty alleviation, and (iii) asset inputs may be
effective in other contexts (for example, where resource degradation and poverty
are tightly interlinked). Our model-based approach and insights offer a
systematic way to review the consequences of the causal mechanisms that
characterize poverty traps in different agricultural contexts and identify
appropriate strategies for rural development challenges.
PMID- 28508078
TI - The exceptional sediment load of fine-grained dispersal systems: Example of the
Yellow River, China.
AB - Sedimentary dispersal systems with fine-grained beds are common, yet the physics
of sediment movement within them remains poorly constrained. We analyze sediment
transport data for the best-documented, fine-grained river worldwide, the Huanghe
(Yellow River) of China, where sediment flux is underpredicted by an order of
magnitude according to well-accepted sediment transport relations. Our
theoretical framework, bolstered by field observations, demonstrates that the
Huanghe tends toward upper-stage plane bed, yielding minimal form drag, thus
markedly enhancing sediment transport efficiency. We present a sediment transport
formulation applicable to all river systems with silt to coarse-sand beds. This
formulation demonstrates a remarkably sensitive dependence on grain size within a
certain narrow range and therefore has special relevance to silt-sand fluvial
systems, particularly those affected by dams.
PMID- 28508079
TI - A twofold quantum delayed-choice experiment in a superconducting circuit.
AB - Wave-particle complementarity lies at the heart of quantum mechanics. To
illustrate this mysterious feature, Wheeler proposed the delayed-choice
experiment, where a quantum system manifests the wave- or particle-like
attribute, depending on the experimental arrangement, which is made after the
system has entered the interferometer. In recent quantum delayed-choice
experiments, these two complementary behaviors were simultaneously observed with
a quantum interferometer in a superposition of being closed and open. We suggest
and implement a conceptually different quantum delayed-choice experiment by
introducing a which-path detector (WPD) that can simultaneously record and
neglect the system's path information, but where the interferometer itself is
classical. Our experiment is realized with a superconducting circuit, where a
cavity acts as the WPD for an interfering qubit. Using this setup, we implement
the first twofold delayed-choice experiment, which demonstrates that the system's
behavior depends not only on the measuring device's configuration that can be
chosen even after the system has been detected but also on whether we a
posteriori erase or mark the which-path information, the latter of which cannot
be revealed by previous quantum delayed-choice experiments. Our results represent
the first demonstration of both counterintuitive features with the same
experimental setup, significantly extending the concept of quantum delayed-choice
experiment.
PMID- 28508080
TI - Direct quantitative measurement of the C?O???H-C bond by atomic force microscopy.
AB - The hydrogen atom-the smallest and most abundant atom-is of utmost importance in
physics and chemistry. Although many analysis methods have been applied to its
study, direct observation of hydrogen atoms in a single molecule remains largely
unexplored. We use atomic force microscopy (AFM) to resolve the outermost
hydrogen atoms of propellane molecules via very weak C?O???H-C hydrogen bonding
just before the onset of Pauli repulsion. The direct measurement of the
interaction with a hydrogen atom paves the way for the identification of three
dimensional molecules such as DNAs and polymers, building the capabilities of AFM
toward quantitative probing of local chemical reactivity.
PMID- 28508081
TI - Evidence and mechanism of efficient thermally activated delayed fluorescence
promoted by delocalized excited states.
AB - The design of organic compounds with nearly no gap between the first excited
singlet (S1) and triplet (T1) states has been demonstrated to result in an
efficient spin-flip transition from the T1 to S1 state, that is, reverse
intersystem crossing (RISC), and facilitate light emission as thermally activated
delayed fluorescence (TADF). However, many TADF molecules have shown that a
relatively appreciable energy difference between the S1 and T1 states (~0.2 eV)
could also result in a high RISC rate. We revealed from a comprehensive study of
optical properties of TADF molecules that the formation of delocalized states is
the key to efficient RISC and identified a chemical template for these materials.
In addition, simple structural confinement further enhances RISC by suppressing
structural relaxation in the triplet states. Our findings aid in designing
advanced organic molecules with a high rate of RISC and, thus, achieving the
maximum theoretical electroluminescence efficiency in organic light-emitting
diodes.
PMID- 28508082
TI - A chlorine-free protocol for processing germanium.
AB - Replacing molecular chlorine and hydrochloric acid with less energy- and risk
intensive reagents would markedly improve the environmental impact of metal
manufacturing at a time when demand for metals is rapidly increasing. We describe
a recyclable quinone/catechol redox platform that provides an innovative
replacement for elemental chlorine and hydrochloric acid in the conversion of
either germanium metal or germanium dioxide to a germanium tetrachloride
substitute. Germanium is classified as a "critical" element based on its high
dispersion in the environment, growing demand, and lack of suitable substitutes.
Our approach replaces the oxidizing capacity of chlorine with molecular oxygen
and replaces germanium tetrachloride with an air- and moisture-stable Ge(IV)
catecholate that is kinetically competent for conversion to high-purity germanes.
PMID- 28508083
TI - Structures of closed and open conformations of dimeric human ATM.
AB - ATM (ataxia-telangiectasia mutated) is a phosphatidylinositol 3-kinase-related
protein kinase (PIKK) best known for its role in DNA damage response. ATM also
functions in oxidative stress response, insulin signaling, and neurogenesis. Our
electron cryomicroscopy (cryo-EM) suggests that human ATM is in a dynamic
equilibrium between closed and open dimers. In the closed state, the PIKK
regulatory domain blocks the peptide substrate-binding site, suggesting that this
conformation may represent an inactive or basally active enzyme. The active site
is held in this closed conformation by interaction with a long helical hairpin in
the TRD3 (tetratricopeptide repeats domain 3) domain of the symmetry-related
molecule. The open dimer has two protomers with only a limited contact interface,
and it lacks the intermolecular interactions that block the peptide-binding site
in the closed dimer. This suggests that the open conformation may be more active.
The ATM structure shows the detailed topology of the regulator-interacting N
terminal helical solenoid. The ATM conformational dynamics shown by the
structures represent an important step in understanding the enzyme regulation.
PMID- 28508085
TI - Intragenic DOK7 deletion detected by whole-genome sequencing in congenital
myasthenic syndromes.
AB - OBJECTIVE: To identify the genetic cause in a patient affected by ptosis and
exercise-induced muscle weakness and diagnosed with congenital myasthenic
syndromes (CMS) using whole-genome sequencing (WGS). METHODS: Candidate gene
screening and WGS analysis were performed in the case. Allele-specific PCR was
subsequently performed to confirm the copy number variation (CNV) that was
suspected from the WGS results. RESULTS: In addition to the previously reported
frameshift mutation c.1124_1127dup, an intragenic 6,261 bp deletion spanning from
the 5' untranslated region to intron 2 of the DOK7 gene was identified by WGS in
the patient with CMS. The heterozygous deletion was suspected based on reduced
coverage on WGS and confirmed by allele-specific PCR. The breakpoints had
microhomology and an inverted repeat, which may have led to the development of
the deletion during DNA replication. CONCLUSIONS: We report a CMS case with
identification of the breakpoints of the intragenic DOK7 deletion using WGS
analysis. This case illustrates that CNVs undetected by Sanger sequencing may be
identified by WGS and highlights their relevance in the molecular diagnosis of a
treatable neurologic condition such as CMS.
PMID- 28508084
TI - Clinicopathologic and molecular spectrum of RNASEH1-related mitochondrial
disease.
AB - OBJECTIVE: Pathologic ribonuclease H1 (RNase H1) causes aberrant mitochondrial
DNA (mtDNA) segregation and is associated with multiple mtDNA deletions. We aimed
to determine the prevalence of RNase H1 gene (RNASEH1) mutations among patients
with mitochondrial disease and establish clinically meaningful genotype-phenotype
correlations. METHODS: RNASEH1 was analyzed in patients with (1) multiple
deletions/depletion of muscle mtDNA and (2) mendelian progressive external
ophthalmoplegia (PEO) with neuropathologic evidence of mitochondrial dysfunction,
but no detectable multiple deletions/depletion of muscle mtDNA. Clinicopathologic
and molecular evaluation of the newly identified and previously reported patients
harboring RNASEH1 mutations was subsequently undertaken. RESULTS: Pathogenic
c.424G>A p.Val142Ile RNASEH1 mutations were detected in 3 pedigrees among the 74
probands screened. Given that all 3 families had Indian ancestry, RNASEH1 genetic
analysis was undertaken in 50 additional Indian probands with variable clinical
presentations associated with multiple mtDNA deletions, but no further RNASEH1
mutations were confirmed. RNASEH1-related mitochondrial disease was characterized
by PEO (100%), cerebellar ataxia (57%), and dysphagia (50%). The ataxia
neuropathy spectrum phenotype was observed in 1 patient. Although the c.424G>A
p.Val142Ile mutation underpins all reported RNASEH1-related mitochondrial
disease, haplotype analysis suggested an independent origin, rather than a
founder event, for the variant in our families. CONCLUSIONS: In our cohort,
RNASEH1 mutations represent the fourth most common cause of adult mendelian PEO
associated with multiple mtDNA deletions, following mutations in POLG, RRM2B, and
TWNK. RNASEH1 genetic analysis should also be considered in all patients with
POLG-negative ataxia neuropathy spectrum. The pathophysiologic mechanisms by
which the c.424G>A p.Val142Ile mutation impairs human RNase H1 warrant further
investigation.
PMID- 28508086
TI - Revisiting classical design in engineering from a perspective of frugality.
AB - The conservative nature of design in engineering has typically unleashed products
fabricated with generous amounts of raw materials. This is epitomized by the
factor of safety whose values higher than unity suggests various uncertainties of
design that are tackled through material padding. This effort proposes a new
factor of safety called the factor of frugality that could be used in ecodesign
and which addresses both rigors of the classical design process and
quantification of savings in materials going into a product. An example of frugal
shaft design together with some other cases has been presented to explain the
working of the factor of frugality. Adoption of the frugality factor would entail
a change in design philosophy whereby designers would constantly make avail of a
rigorous design process coupled with material-saving schemes for realizing
products that are benign to the environment. Such a change in the foundations of
design would abet the stewardship of earth in avoiding planetary boundaries since
engineering influences a significant proportion of human endeavors.
PMID- 28508087
TI - The Vitamin D for Enhancing the Immune System in Cystic Fibrosis (DISC) trial:
Rationale and design of a multi-center, double-blind, placebo-controlled trial of
high dose bolus administration of vitamin D3 during acute pulmonary exacerbation
of cystic fibrosis.
AB - Vitamin D deficiency is highly prevalent in children and adults with cystic
fibrosis (CF). Recent studies have found an association between vitamin D status
and risk of pulmonary exacerbations in children and adults with CF. The ongoing
Vitamin D for enhancing the Immune System in Cystic fibrosis (DISC) study is a
multi-center, double-blind, randomized, placebo-controlled trial that will test
the hypothesis of whether high dose vitamin D given as a single oral bolus of
250,000 IU to adults with CF during a pulmonary exacerbation followed by a
maintenance dose of vitamin D will improve time to next pulmonary exacerbation
and re-hospitalization, improve survival and lung function compared to placebo
and reduce the rates of pulmonary exacerbation,. Subjects will be randomized 1:1
at each clinical site to vitamin D or placebo within 72 hours of hospital
admission for pulmonary exacerbation. Clinical follow-up visits will occur at 1,
2, 3, and 7 days, and 1, 3, 6 and 12 months after randomization. Blood and sputum
will be collected and determination of clinical outcomes will be assessed at each
visit. The primary endpoint will be the time to next pulmonary exacerbation
requiring antibiotics, re-hospitalization or death. The secondary endpoints will
include lung function assessed by forced expiratory volume in 1 second (FEV1),
blood markers of inflammatory cytokines, anti-microbial peptide expression by
peripheral blood mononuclear cells and circulating concentrations in blood. Other
exploratory endpoints will examine the phenotype of neutrophils and
monocyte/macrophages in sputum. Nutritional status will be assessed by 3 day food
records and food frequency questionnaire.
PMID- 28508089
TI - Response to Sabour: Dual-energy X-ray absorptiometry and fracture prediction in
patients with spinal cord injuries and disorders: methodological issues.
PMID- 28508088
TI - Characterization of the molar mass distribution of macromolecules in beer for
different mashing processes using asymmetric flow field-flow fractionation (AF4)
coupled with multiple detectors.
AB - The macromolecular composition of beer is largely determined by the brewing and
the mashing process. It is known that the physico-chemical properties of
proteinaceous and polysaccharide molecules are closely related to the mechanism
of foam stability. Three types of "American pale ale" style beer were prepared
using different mashing protocols. The foam stability of the beers was assessed
using the Derek Rudin standard method. Asymmetric flow field-flow fractionation
(AF4) in combination with ultraviolet (UV), multiangle light scattering (MALS)
and differential refractive index (dRI) detectors was used to separate the
macromolecules present in the beers and the molar mass (M) and molar mass
distributions (MD) were determined. Macromolecular components were identified by
enzymatic treatments with beta-glucanase and proteinase K. The MD of beta-glucan
ranged from 106 to 108 g/mol. In addition, correlation between the beer's
composition and foam stability was investigated (increased concentration of
protein and beta-glucan was associated with increased foam stability).
PMID- 28508090
TI - [Johan Gadolin - namesake for the element gadolinium].
PMID- 28508091
TI - [MR spectroscopy in metabolic disorders of the brain].
AB - CLINICAL ISSUE: Metabolic disorders of the brain often present a particular
challenge for the neuroradiologist, since the disorders are rare, changes on
conventional MR are often non-specific and there are numerous differential
diagnoses for the white substance lesions. STANDARD RADIOLOGICAL METHODS: As a
complementary method to conventional brain MRI, MR spectroscopy may help to
reduce the scope of the differential diagnosis. Entities with specific MR
spectroscopy patterns are Canavan disease, maple syrup urine disease, nonketotic
hyperglycinemia and creatine deficiency.
PMID- 28508092
TI - A metabonomic analysis on the response of Enterobacter cloacae from coastal
outfall for land-based pollutant under phoxim stress.
AB - Enterobacter cloacae is an opportunistic pathogen widely distributed in human and
animal intestinal systems. The secretion of extended-spectrum beta-lactamases
(ESBLs) and cephalosporinase (AmpC) endows E. cloacae with strong drug
resistance. In a previous study by our group, protein expression of E. cloacae
under phoxim stress was measured by two-dimensional electrophoresis. Here,
nuclear magnetic resonance was used to detect differences in E. cloacae
metabonomics when under phoxim stress. We determined that there are 29 types of
metabolites that differ between phoxim stress and normal culture conditions.
Among these, 6 types of metabolites were upregulated in the phoxim stress group,
and 23 types of metabolites were inhibited. Though enrichment analysis, seven
pathways were identified by different expression levels of metabolites, which
were involved in DNA and RNA synthesis, DNA damage repair, antioxidation and
functions of the cell membrane and cell wall. The mechanism underlying how phoxim
affects E. cloacae was determined by studying the results of both two-dimensional
electrophoresis in our prior work and the analysis of E. cloacae metabonomic
changes under phoxim stress.
PMID- 28508093
TI - Expression of Concern: Modulation of gut microbiota by antibiotics improves
insulin signalling in high-fat fed mice.
PMID- 28508094
TI - [Current SHI physician legislation: succession rules for surgical seats :
Surgical vacancies can be filled with orthopedic/trauma surgery specialists only
within narrow limits].
AB - It is a physician's certified continuing medical education category-rather than
their actual medical activity, in this case in the field of trauma surgery-that
is decisive in filling statutory health insurance (SHI) practice vacancies. This
evaluation arising from S16 of the requirement planning guideline applies
accordingly when filling physician vacancies. Thus physician vacancies or
statutory health insurance (SHI) practice places can only be filled by a
physician in the same physician group in line with requirement planning. Scope
for argumentation initially remains in the context of filling surgical SHI
physician vacancies where the ceding physician is certified as an accident
insurance consultant.
PMID- 28508095
TI - Estimation of glomerular filtration rate in cancer patients with abnormal body
composition and relation with carboplatin toxicity.
AB - PURPOSE: Carboplatin clearance is correlated with glomerular filtration rate
(GFR) and usually estimated with creatinine clearance using Cockcroft-Gault (CG)
formula. Because plasma creatinine level is highly correlated with muscle mass,
we hypothesized that an abnormal body composition with a low lean body mass (LBM)
percentage [(LBM/weight) * 100] may result in inadequate carboplatin dosing.
Serum cystatin C is an alternative marker of GFR, not affected by muscle mass. We
aimed to investigate the influence of total LBM and LBM percentage on GFR
calculation, using creatinine (CrCl) or cystatin C (GFRcysC-creat) in cancer
patients. METHODS: Pretreatment serum creatinine and cystatin C were
prospectively measured in consecutive patients. CrCl (CG formula), GFRcysC-creat
(CKD-EPI creatinine-cystatin equation), and LBM (CT scan) were calculated. Severe
thrombocytopenia post-carboplatin were analyzed. RESULTS: In 131 patients without
renal insufficiency, LBM was correlated with creatinine (r = 0.30, p < 0.005) but
not with cystatin C (r = -0.07, p = 0.43). In patients with the lowest LBM
percentage, the CrCl was significantly higher than GFRcysC-creat indicating an
overestimation of GFR with creatinine (p = 0.0004). In 24 patients treated with
carboplatin AUC 5 (mg/ml min) +/- paclitaxel, the risk of severe thrombocytopenia
was associated with lower LBM percentage (p = 0.0002) and higher CrCl/GFRcysC
creat ratio (p = 0.006). By ROC analysis, the CrCl/GFRcysC-creat ratio threshold
predicting severe thrombocytopenia was 1.23. CONCLUSIONS: A low LBM percentage
increases the risk of inadequate GFR calculation by CG formula, and carboplatin
overdosage with severe thrombocytopenia. High CrCl/GFRcysC-creat ratio allows the
identification of these patients.
PMID- 28508096
TI - [Off-label biologic therapy of ANCA-associated and non-ANCA-associated small
vessel vasculitis : Efficacy and safety analysis of a national registry
(GRAID2)].
AB - OBJECTIVE: To evaluate the clinical efficacy and safety of off-label biological
therapies in patients with ANCA-associated vasculitis (AAV) and non-ANCA
associated small-vessel vasculitis (nAAV) in clinical practice. METHODS: The
German Registry in Autoimmune Diseases 2 (GRAID2) is a national, retrospective,
non-interventional, multicentre observational study (August 2006 until December
2013) on patients with autoimmune diseases refractory to standard
immunosuppressive therapy treated with off-label biologicals. RESULTS: Data from
64 patients (20.6% of all GRAID2 patients) were collected: 54 patients (84.4%)
had ANCA-associated vasculitis (AAV) and 10 patients (15.6%) had non-ANCA
associated small-vessel vasculitis (nAAV). Of the AAV patients, 96.3% were
treated off-label with rituximab (RTX) and 3.7% with tumor necrosis factor alpha
(TNFalpha)-inhibitors. Of patients with nAAV, 30% were treated with RTX, 60% with
TNFalpha-inhibitors, and 10% with tocilizumab. The main reasons for off-label
biological treatment in AAV patients were pulmonary, renal, or ear, nose, and
throat involvement. These manifestations clearly improved in most patients after
off-label biological therapy was initiated. Daily glucocorticoid dosage could be
reduced. The off-label biological therapy was generally well tolerated. In AAV
patients, 4.18 severe infections per 100 patient years were observed. There was
one death in the nAAV group caused by fungal infection and ileus. A correlation
between this fatality and RTX treatment was regarded as possible. CONCLUSION:
Safety and efficacy of off-label RTX-treatment in AAV-patients could be assessed
in the GRAID2 data. Results point to good efficacy and safety of RTX in this
special patient cohort and support the approval of RTX for AAV induction therapy.
PMID- 28508098
TI - Patient mortality following alcohol use and trauma: a propensity-matched
analysis.
AB - OBJECTIVE: To examine the outcomes of trauma patients who tested positive for
alcohol at the time of hospital arrival versus those who tested negative.
METHODS: Data were pulled from the National Trauma Data Bank (2007-2010). All
injured patients who were >=14 years of age, sustained a "blunt" or "penetrating"
injury, had complete systolic blood pressure (SBP) and heart rate (HR) records,
were taken to a level 1 or 2 trauma center, and who received a confirmed blood
alcohol test were included in the study. Any blood alcohol concentration (BAC)
above the legal limit (>=0.08 g/dL) was considered "positive" for alcohol, and if
no alcohol was identified it was considered "negative". Patients' demography and
clinical information were compared across groups using Chi-square and Wilcoxon
rank sum tests. Logistic regression, propensity score matching, and a follow-up
paired analysis were also performed. RESULTS: Of 279,460 total patients, around
one-third of the patients (92,960) tested positive for BAC. There were clear
demographic differences found between the two groups regarding age, gender, race,
and injury type. There was also a significantly higher mortality rate (4.3 vs.
3.1%, P < 0.001) and a longer hospital length of stay (4 vs. 3 days, P < 0.001)
found in the alcohol-negative group. Propensity score matching was also performed
resulting in 92,959 patients per group. Using the paired data, the overall
mortality observed was 3.1 vs. 3.3% (P = 0.035) between the alcohol-positive and
alcohol-negative groups, respectively. There was no significant difference noted
in the total hospital length of stay (median: 3 vs. 4 days, P = 0.84).
CONCLUSION: Patients who tested positive for alcohol following a traumatic injury
showed no clinically significant reduction in mortality and no significant
difference in total hospital length of stay.
PMID- 28508097
TI - Development of SSR markers and identification of major quantitative trait loci
controlling shelling percentage in cultivated peanut (Arachis hypogaea L.).
AB - KEY MESSAGE: A total of 204,439 SSR markers were developed in diploid genomes,
and 25 QTLs for shelling percentage were identified in a RIL population across 4
years including five consistent QTLs. Cultivated peanut (Arachis hypogaea L.) is
an important grain legume providing edible oil and protein for human nutrition.
Genome sequences of its diploid ancestors, Arachis duranensis and A. ipaensis,
were reported, but their SSRs have not been well exploited and utilized hitherto.
Shelling percentage is an important economic trait and its improvement has been
one of the major objectives in peanut breeding programs. In this study, the
genome sequences of A. duranensis and A. ipaensis were used to develop SSR
markers, and a mapping population (Yuanza 9102 * Xuzhou 68-4) with 195
recombinant inbred lines was used to map QTLs controlling shelling percentage.
The numbers of newly developed SSR markers were 84,383 and 120,056 in the A.
duranensis and A. ipaensis genomes, respectively. Genotyping of the mapping
population was conducted with both newly developed and previously reported
markers. QTL analysis using the phenotyping data generated in Wuhan across four
consecutive years and genotyping data of 830 mapped loci identified 25 QTLs with
4.46-17.01% of phenotypic variance explained in the four environments. Meta
analysis revealed five consistent QTLs that could be detected in at least two
environments. Notably, the consistent QTL cqSPA09 was detected in all four
environments and explained 10.47-17.01% of the phenotypic variance. The
segregation in the progeny of a residual heterozygous line confirmed that the
cpSPA09 locus had additive effect in increasing shelling percentage. These
consistent and major QTL regions provide opportunity not only for further gene
discovery, but also for the development of functional markers for breeding.
PMID- 28508099
TI - Giant congenital melanocytic nevi and malignant transformation: a case for early
radical intervention.
AB - The purpose of this paper is to highlight the risk of early malignant
transformation in infants with giant congenital melanocytic nevi (GN) and
demonstrate the potential for earlier intervention with aggressive surgery. We
describe the case of a child born with a GN who developed a metastatic melanoma
early in life, despite early commencement of resection of the nevus. This is
contrasted against a second case of a child in which a more radical management
was conducted. Despite early commencement of serial resection of the GN, the
first child in this series died of metastatic melanoma prior to complete excision
of the nevus. With the second child, radical excision combined with the use of
IntegraTM and negative pressure wound therapy allowed total removal of the GN
within the first 6 months of life.
PMID- 28508100
TI - Cervical radiculopathy combined with cervical myelopathy: prevalence and
characteristics.
AB - Patients with cervical myelopathy may experience symptoms of radiculopathy, and
it is not easy to determine whether these symptoms are caused by the myelopathy
itself or by a radiculopathy accompanied by root compression. Therefore, we aimed
to investigate the prevalence of radiculopathy combined with cervical myelopathy
and to evaluate the characteristics of cervical myelopathy with or without
radiculopathy. We enrolled 127 patients with cervical myelopathy in this
retrospective study and reviewed their medical records and magnetic resonance
imaging findings. They were divided into two groups according to the presence of
cervical radiculopathy, and their age, sex, involved spinal segment, cord signal
change, surgical method, clinical status were compared, and postsurgical recovery
was compared using four clinical questionnaires. The incidence and level of
radiculopathy combined with myelopathy were investigated. Combined cervical
radiculopathy and myelopathy was diagnosed in 66 patients (51.9%, group 1),
whereas 61 patients did not have radiculopathy (group 2). There was no difference
in sex, age, cord signal change, preoperative Japanese Orthopedic Association
score, neck disability index, and neck visual analogue scale (VAS) between the
two groups, but group 1 showed higher preoperative arm VAS score (p = 0.001).
Postoperative arm and neck VAS scores were significantly improved in group 1 (p =
0.001 and 0.009). Half of the patients had combined cervical myelopathy and
radiculopathy. A high preoperative arm VAS score was a characteristic of
radiculopathy combined with myelopathy.
PMID- 28508103
TI - To be or not to be rheumatologist: survey among Belgian medical students and
internal medicine trainees: what do certified rheumatologists think about the
current rheumatology training program?
AB - In several countries, there have been increasing concerns over the years that
fewer medical students or trainees choose rheumatology as a specialty. The aim of
this three-step survey is to study the motivational factors for students and
trainees in internal medicine to choose for rheumatology as a future career
option and the idea among experienced rheumatologists about the needs for changes
in the training program. An online survey was distributed among students in
medical training (in the final 3 years) and trainees in internal medicine from
the Ghent University and University Hospital. Questions concerned the level of
clinical exposure to rheumatology and the motivation about becoming
rheumatologist. Next, experienced rheumatologists were asked about the needs to
change the current training. Descriptive data are shown and chi-squared tests
were calculated to assess differences between groups (based on gender and
exposure). Logistic regression was performed to study associations between
demographic variables and choosing rheumatology as career. Only a minority of
students (17%) and about half of trainees (45%) were ever exposed to
rheumatology. Only 11% of students and 17% of trainees considered becoming
rheumatologist. There was no difference in choice based on gender but previous
exposure seemed to play an important role, and especially during the pre
specialty years. Univariate logistic regression identified the year of training
and exposure as predictors for choosing rheumatology. Multivariate analysis only
retained exposure as significantly associated (odds ratio (95% CI) = 2.88 (1.51
12.58)). Rheumatology is considered to be a fascinating discipline among Belgian
students and trainees. Exposure during pre-specialty years is the strongest
predictor for choosing rheumatology as future career option.
PMID- 28508101
TI - In-depth clinico-pathological examination of RNA foci in a large cohort of
C9ORF72 expansion carriers.
AB - A growing body of evidence suggests that a loss of chromosome 9 open reading
frame 72 (C9ORF72) expression, formation of dipeptide-repeat proteins, and
generation of RNA foci contribute to disease pathogenesis in amyotrophic lateral
sclerosis and frontotemporal dementia. Although the levels of C9ORF72 transcripts
and dipeptide-repeat proteins have already been examined thoroughly, much remains
unknown about the role of RNA foci in C9ORF72-linked diseases. As such, we
performed a comprehensive RNA foci study in an extensive pathological cohort of
C9ORF72 expansion carriers (n = 63). We evaluated two brain regions using a newly
developed computer-automated pipeline allowing recognition of cell nuclei and RNA
foci (sense and antisense) supplemented by manual counting. In the frontal
cortex, the percentage of cells with sense or antisense RNA foci was 26 or 12%,
respectively. In the cerebellum, 23% of granule cells contained sense RNA foci
and 1% antisense RNA foci. Interestingly, the highest percentage of cells with
RNA foci was observed in cerebellar Purkinje cells (~70%). In general, more cells
contained sense RNA foci than antisense RNA foci; however, when antisense RNA
foci were present, they were usually more abundant. We also observed that an
increase in the percentage of cells with antisense RNA foci was associated with a
delayed age at onset in the frontal cortex (r = 0.43, p = 0.003), whereas no
other associations with clinico-pathological features were seen. Importantly, our
large-scale study is the first to provide conclusive evidence that RNA foci are
not the determining factor of the clinico-pathological variability observed in
C9ORF72 expansion carriers and it emphasizes that the distribution of RNA foci
does not follow the pattern of neurodegeneration, stressing the complex interplay
between different aspects of C9ORF72-related diseases.
PMID- 28508102
TI - Role of lymph node dissection during radical nephroureterectomy for upper urinary
tract urothelial cancer: multi-institutional large retrospective study JCOG1110A.
AB - PURPOSE: To evaluate the impact of lymph node dissection (LND) on clinical
outcome during radical nephroureterectomy (RNU) for patients with upper urinary
tract urothelial cancer (UTUC). METHODS: We, the Urologic Oncology Study Group of
the Japan Clinical Oncology Group (JCOG), retrospectively collected data from
patients with non-metastatic UTUC who underwent RNU in 30 centers in 1995-2009.
Ineligible patients and patients with previous and/or synchronous bladder cancer
were excluded, and the remaining 2037 patients were analyzed. We compared overall
and cancer-specific mortality between patients who underwent LND (LND group) and
those without LND (no-LND group). RESULTS: Among 2037 patients, LND was performed
in 1046 (51.4%) patients, and 223 (10.9%) patients had pathological node-positive
(pN+) disease. All-cause mortality was observed in 503 patients (24.7%) during
follow-up (median 45.8 months), including 363 patients (17.8%) who died of UTUC.
Patients with pN+ disease showed significantly shorter overall survival (OS)
compared with pN0 patients, and the estimated 5-year OS for pN+ patients was 30%.
Older age, >=cT3, and clinical node-positive disease were found as preoperative
predictors for pN+ disease by multivariate analysis. In the comparison of OS and
cancer-specific mortality between LND and no-LND groups, there was no significant
improvement by LND in multivariate analysis. The median number of lymph nodes
removed was six (IQR 3-11). There was no significant association between the
number of lymph nodes removed and OS. CONCLUSIONS: The present study indicates
that there is no therapeutic benefit of LND during RNU for UTUC, although
pathologically positive LN status can predict poor prognosis.
PMID- 28508105
TI - Unexplained changes on a psychiatric pregnancy study.
PMID- 28508104
TI - Quercetin inhibits gout arthritis in mice: induction of an opioid-dependent
regulation of inflammasome.
AB - We investigated the anti-inflammatory and analgesic effects of quercetin in
monosodium urate crystals (MSU)-induced gout arthritis, and the sensitivity of
quercetin effects to naloxone, an opioid receptor antagonist. Mice were treated
with quercetin, and mechanical hyperalgesia was assessed at 1-24 h after MSU
injection. In vivo, leukocyte recruitment, cytokine levels, oxidative stress,
NFkappaB activation, and gp91phox and inflammasome components (NLRP3, ASC, Pro
caspase-1, and Pro-IL-1beta) mRNA expression by qPCR were determined in the knee
joints at 24 h after MSU injection. Inflammasome activation was determined, in
vitro, in lipopolysaccharide-primed macrophages challenged with MSU. Quercetin
inhibited MSU-induced mechanical hyperalgesia, leukocyte recruitment, TNFalpha
and IL-1beta production, superoxide anion production, inflammasome activation,
decrease of antioxidants levels, NFkappaB activation, and inflammasome components
mRNA expression. Naloxone pre-treatment prevented all the inhibitory effects of
quercetin over MSU-induced gout arthritis. These results demonstrate that
quercetin exerts analgesic and anti-inflammatory effect in the MSU-induced
arthritis in a naloxone-sensitive manner.
PMID- 28508108
TI - Stone in ectopic pelvic pancake kidney: a surgical challenge overcome by robotic
surgery.
PMID- 28508106
TI - Differential effects of pair housing on voluntary nicotine consumption: a
comparison between male and female adolescent rats.
AB - RATIONALE: Tobacco smoking occurs in a wide array of social circumstances. Social
support for quitting is generally used to stop smoking, while peer interactions
may be a crucial factor in triggering tobacco use among adolescents. OBJECTIVES:
To determine the role of social factors on nicotine dependence, we compared
single- and pair-housed rats subjected to voluntary oral nicotine consumption
tests. METHODS: Six-week-old adolescent rats were subjected to experimental
procedures and assigned to one of the following groups: a male single group, a
male pair group with a sibling, a female single group, and a female pair group
with a sibling. To measure voluntary nicotine intake, we adopted a two-bottle
free-choice paradigm for each two days using 25 MUg/ml and 100 MUg/ml nicotine
solution. RESULTS: There were no differences in change in body weight or food
intake between the two groups of either sex. Pair-housed female rats showed a
reduction in nicotine consumption and preference for both low- and high-dose
nicotine solution, while pair-housed male rats showed only reduced consumption
and preference for high-dose nicotine solution, but not low-dose solution, as
compared to single-housed male rats. CONCLUSIONS: Nicotine consumption is sex
dependently controlled by the social circumstances of rats. This study broadens
our perspectives on the role of social interactions as a therapeutic strategy to
treat nicotine addiction-related behaviors depending on sex.
PMID- 28508107
TI - Memantine add-on to antipsychotic treatment for residual negative and cognitive
symptoms of schizophrenia: a meta-analysis.
AB - RATIONALE: We examined whether memantine add-on to antipsychotic treatment is
beneficial in schizophrenia treatment. OBJECTIVE: This systematic review and meta
analysis aimed to achieve stronger evidence on the efficacy and safety of
memantine add-on for treating schizophrenia. METHODS: We analyzed double-blind,
randomized, placebo-controlled trials of memantine add-on treatment in
schizophrenia patients receiving antipsychotics. The primary outcomes were
amelioration of negative symptoms and all-cause discontinuation. Dichotomous
outcomes are presented as risk ratios (RRs), and continuous outcomes are
presented as mean differences (MDs) or standardized mean differences (SMDs).
RESULTS: Eight studies (n = 448) were included. Although memantine add-on
treatment was superior to placebo for ameliorating negative symptoms (SMD =
0.96, p = 0.006, I 2 = 88%; N = 7, n = 367) in the Positive and Negative Syndrome
Scale general subscale (MD = -1.62, p = 0.002, I 2 = 0%; N = 4, n = 151) and Mini
Mental Status Examination score (MD = -3.07, p < 0.0001, I 2 = 21%; N = 3, n =
83), there were no statistically significant differences in the amelioration of
overall (SMD = -0.75, p = 0.06, I 2 = 86%; N = 5, n = 271), positive (SMD =
0.46, p = 0.07, I 2 = 80%; N = 7, n = 367), and depressive symptoms (SMD =
0.127, p = 0.326, I 2 = 0%; N = 4, n = 201); all-cause discontinuation (RR =
1.34, p = 0.31, I 2 = 0%; N = 8, n = 448); and individual adverse events
(fatigue, dizziness, headache, nausea, constipation) between the groups. For
negative symptoms, the significant heterogeneity disappeared when risperidone
studies alone were considered (I 2 = 0%). However, memantine add-on treatment
remained superior to placebo (SMD = -1.29, p = 0.00001). Meta-regression analysis
showed that patient age was associated with memantine-associated amelioration of
negative symptoms (slope = 0.171, p = 0.0206). CONCLUSIONS: Memantine add-on
treatment may be beneficial for treating psychopathological symptoms (especially
negative symptoms) in schizophrenia patients. The negative-symptom effect size
may be associated with younger adult schizophrenia patients.
PMID- 28508109
TI - Solvent-accessibility of discrete residue positions in the polypeptide hormone
glucagon by 19F-NMR observation of 4-fluorophenylalanine.
AB - The amino acid 4-fluoro-L-phenylalanine (4F-Phe) was introduced at the positions
of Phe6 and Phe22 in the 29-residue polypeptide hormone glucagon by expressing
glucagon in E. coli in the presence of an excess of 4F-Phe. Glucagon regulates
blood glucose homeostasis by interaction with the glucagon receptor (GCGR), a
class B GPCR. By referencing to the 4F-Phe chemical shifts at varying D2O
concentrations, the solvent exposure of the two Phe sites along the glucagon
sequence was determined, showing that 4F-Phe6 was fully solvent exposed and 4F
Phe22 was only partially exposed. The incorporation of fluorine atoms in
polypeptide hormones paves the way for novel studies of their interactions with
membrane-spanning receptors, specifically by differentiating between effects on
the solvent accessibility, the line shapes, and the chemical shifts from
interactions with lipids, detergents and proteins. Studies of interactions of
GCGR with ligands in solution is at this point of keen interest, given that
recent crystallographic studies revealed that an apparent small molecule
antagonist actually binds as an allosteric effector at a distance of ~20 A from
the orthosteric ligand binding site (Jazayeri et al., in Nature 533:274-277,
2016).
PMID- 28508110
TI - Joint non-uniform sampling of all incremented time delays for quicker acquisition
in protein relaxation studies.
AB - NMR relaxometry plays crucial role in studies of protein dynamics. The
measurement of longitudinal and transverse relaxation rates of [Formula: see
text]N is the main source of information on backbone motions. However, even the
most basic approach exploiting a series of [Formula: see text]N HSQC spectra can
require several hours of measurement time. Standard non-uniform sampling (NUS),
i.e. random under-sampling of indirect time domain, typically cannot reduce this
by more than 2-4[Formula: see text] due to relatively low "compressibility" of
these spectra. In this paper we propose an extension of NUS to relaxation delays.
The two-dimensional space of [Formula: see text]/[Formula: see text] is sampled
in a way similar to NUS of [Formula: see text]/[Formula: see text] domain in 3D
spectra. The signal is also processed in a way similar to that known from 3D NUS
spectra i.e. using one of the most popular compressed sensing algorithms,
iterative soft thresholding. The 2D Fourier transform matrix is replaced with
mixed inverse Laplace-Fourier transform matrix. The peak positions in resulting
3D spectrum are characterized by two frequency coordinates and relaxation rate
and thus no additional fitting of exponential curves is required. The method is
tested on three globular proteins, providing satisfactory results in a time
corresponding to acquisition of two conventional [Formula: see text]N HSQC
spectra.
PMID- 28508111
TI - Effect of high-intensity aerobic exercise on aerobic fitness and HbA1c in
patients with type 2 diabetes.
PMID- 28508112
TI - Response to comments on "High-intensity aerobic interval training improves
aerobic fitness and HbA1c among persons diagnosed with type 2 diabetes".
PMID- 28508113
TI - Doubly labelled water assessment of energy expenditure: principle, practice, and
promise.
AB - The doubly labelled water method for the assessment of energy expenditure was
first published in 1955, application in humans started in 1982, and it has become
the gold standard for human energy requirement under daily living conditions. The
method involves enriching the body water of a subject with heavy hydrogen (2H)
and heavy oxygen (18O), and then determining the difference in washout kinetics
between both isotopes, being a function of carbon dioxide production. In
practice, subjects get a measured amount of doubly labelled water (2H 218 O) to
increase background enrichment of body water for 18O of 2000 ppm with at least
180 ppm and background enrichment of body water for 2H of 150 ppm with 120 ppm.
Subsequently, the difference between the apparent turnover rates of the hydrogen
and oxygen of body water is assessed from blood-, saliva-, or urine samples,
collected at the start and end of the observation interval of 1-3 weeks. Samples
are analyzed for 18O and 2H with isotope ratio mass spectrometry. The doubly
labelled water method is the indicated method to measure energy expenditure in
any environment, especially with regard to activity energy expenditure, without
interference with the behavior of the subjects. Applications include the
assessment of energy requirement from total energy expenditure, validation of
dietary assessment methods and validation of physical activity assessment methods
with doubly labelled water measured energy expenditure as reference, and studies
on body mass regulation with energy expenditure as a determinant of energy
balance.
PMID- 28508115
TI - When kinesthetic information is neglected in learning a Novel bimanual rhythmic
coordination.
AB - Many studies have shown that rhythmic interlimb coordination involves perception
of the coupled limb movements, and different sensory modalities can be used.
Using visual displays to inform the coupled bimanual movement, novel bimanual
coordination patterns can be learned with practice. A recent study showed that
similar learning occurred without vision when a coach provided manual guidance
during practice. The information provided via the two different modalities may be
same (amodal) or different (modality specific). If it is different, then learning
with both is a dual task, and one source of information might be used in
preference to the other in performing the task when both are available. In the
current study, participants learned a novel 90 degrees bimanual coordination
pattern without or with visual information in addition to kinesthesis. In
posttest, all participants were tested without and with visual information in
addition to kinesthesis. When tested with visual information, all participants
exhibited performance that was significantly improved by practice. When tested
without visual information, participants who practiced using only kinesthetic
information showed improvement, but those who practiced with visual information
in addition showed remarkably less improvement. The results indicate that (1) the
information is not amodal, (2) use of a single type of information was preferred,
and (3) the preferred information was visual. We also hypothesized that older
participants might be more likely to acquire dual task performance given their
greater experience of the two sensory modes in combination, but results were
replicated with both 20- and 50-year-olds.
PMID- 28508114
TI - Oral L-menthol reduces thermal sensation, increases work-rate and extends time to
exhaustion, in the heat at a fixed rating of perceived exertion.
AB - PURPOSE: The study investigated the effect of a non-thermal cooling agent, L
menthol, on exercise at a fixed subjective rating of perceived exertion (RPE) in
a hot environment. METHOD: Eight male participants completed two trials at an
exercise intensity between 'hard' and 'very hard', equating to 16 on the RPE
scale at ~35 degrees C. Participants were instructed to continually adjust their
power output to maintain an RPE of 16 throughout the exercise trial, stopping
once power output had fallen by 30%. In a randomized crossover design, either L
menthol or placebo mouthwash was administered prior to exercise and at 10 min
intervals. Power output, [Formula: see text]O2, heart rate, core and skin
temperature was monitored, alongside thermal sensation and thermal comfort.
Isokinetic peak power sprints were conducted prior to and immediately after the
fixed RPE trial. RESULTS: Exercise time was greater (23:23 +/- 3:36 vs. 21:44 +/-
2:32 min; P = 0.049) and average power output increased (173 +/- 24 vs. 167 +/-
24 W; P = 0.044) in the L-menthol condition. Peak isokinetic sprint power
declined from pre-post trial in the L-menthol l (9.0%; P = 0.015) but not in the
placebo condition (3.4%; P = 0.275). Thermal sensation was lower in the L-menthol
condition (P = 0.036), despite no changes in skin or core temperature (P > 0.05).
CONCLUSION: These results indicate that a non-thermal cooling mouth rinse lowered
thermal sensation, resulting in an elevated work rate, which extended exercise
time in the heat at a fixed RPE.
PMID- 28508116
TI - Comparing visual search and eye movements in bilinguals and monolinguals.
AB - Recent research has suggested that bilinguals show advantages over monolinguals
in visual search tasks, although these findings have been derived from global
behavioral measures of accuracy and response times. In the present study we
sought to explore the bilingual advantage by using more sensitive eyetracking
techniques across three visual search experiments. These spatially and temporally
fine-grained measures allowed us to carefully investigate any nuanced attentional
differences between bilinguals and monolinguals. Bilingual and monolingual
participants completed visual search tasks that varied in difficulty. The
experiments required participants to make careful discriminations in order to
detect target Landolt Cs among similar distractors. In Experiment 1, participants
performed both feature and conjunction search. In Experiments 2 and 3,
participants performed visual search while making different types of speeded
discriminations, after either locating the target or mentally updating a
constantly changing target. The results across all experiments revealed that
bilinguals and monolinguals were equally efficient at guiding attention and
generating responses. These findings suggest that the bilingual advantage does
not reflect a general benefit in attentional guidance, but could reflect more
efficient guidance only under specific task demands.
PMID- 28508117
TI - Single-Center Experience Using the 3MAX Reperfusion Catheter for the Treatment of
Acute Ischemic Stroke with Distal Arterial Occlusions.
AB - PURPOSE: Most recent guidelines recommend the use of stent retriever devices in
endovascular treatment of acute ischemic stroke with large vessel occlusion
(LVO). Recently published data reported convincing results with thromboaspiration
devices such as the Penumbra System (Penumbra, Alameda, CA, USA) combined with
supple reperfusion catheters by using the ADAPT (A Direct Aspiration First-Pass
Thrombectomy) technique. The aim of this study was to report our initial
experience with the 3MAX (3.8 F) reperfusion catheter for the recanalization of
distal intracranial arteries. METHODS: From August 2015 to December 2016, 32
consecutive patients (16 females, 50%; mean age = 67.4 +/- 18.7 years, range: 22
91) for 38 distal occlusions underwent mechanical thrombectomy (MT) by
thromboaspiration using the 3MAX. Median NIHSS score at admission was 14 (IQR: 9
19). Distal occlusions were distributed as follows: M2 (n: 23), M3 (n: 6), P1 (n:
3), P2 (n: 2), P3 (n: 2), A3 segment (n: 1) and superior cerebellar artery (n:
1). RESULTS: In 1/38 (2.6%) target artery, the 3MAX could not be navigated. Of
the 37 (59.5%) remaining arteries, 22 were successfully reperfused (TICI 2b/3)
after ADAPT with the 3MAX alone. Additional stent retriever thrombectomy allowed
a 76.3% final reperfusion rate. Good functional outcome (mRS <=2) was obtained in
45.5% of patients at 3 months. Three (9.4%) 3MAX-related complications occurred:
2 emboli to new territory (ENT) and one vascular perforation. CONCLUSIONS: The
3MAX is well-navigable in distal arteries making it useful as a frontline
technique. However, the reperfusion rate with the 3MAX catheter alone seems lower
than the ones reported with stent retrievers for such distal occlusions.
PMID- 28508118
TI - Effects of aeration on metabolic profiles of Mortierella alpina during the
production of arachidonic acid.
AB - To investigate the metabolic regulation against oxygen supply, comparative
metabolomics was performed to explore the metabolic responses of Mortierella
alpina in the process of arachidonic acid (ARA) production. More than 110
metabolites involved in Embden-Meyerhof-Parnas pathway, pentose phosphate
pathway, tricarboxylic acid cycle, inositol phosphate metabolism, fatty acid
biosynthesis, and amino acid metabolism were identified by gas chromatography
mass spectrometry. Samples at different aeration rates were clearly distinguished
by principal components analysis and partial least squares analysis, indicating
that oxygen supply had a profound effect on the metabolism of M. alpina. Eleven
major metabolites were identified as potential biomarkers to be primarily
responsible for the difference of metabolism. Further study of metabolic changes
with the relevant pathways demonstrated that the levels of several intermediate
metabolites in relation to central carbon metabolism changed remarkably via both
processes and citrate and malate was supposed to play vital roles in
polyunsaturated acid (PUFA) synthesis. Increase of myo-inositol and sorbitol were
probably for osmo-regulation and redox balance, while enhanced phosphoric acid
and pyroglutamic acid were supposed to have function in the activation of signal
transduction pathway for stress resistance. The present study provides a novel
insight into the metabolic responses of M. alpina to aeration rates and the
metabolic characteristics during the ARA fermentation.
PMID- 28508119
TI - Lipoprotein(a): A Lipoprotein Whose Time Has Come.
AB - OPINION STATEMENT: Cardiovascular disease is a leading cause of morbidity and
mortality in the USA and around the world. While we are now able to achieve
significant low-density lipoprotein cholesterol (LDL-C) lowering with current
therapies, many patients remain at risk for cardiovascular disease (CVD).
Elevated lipoprotein(a) [Lp(a)] has been shown to be an independent risk factor
for CVD and accounts for some of the residual CVD risk after LDL-C lowering in
several large clinical trials. Moreover, there is now strong evidence supporting
the causal relationship between Lp(a) and aortic stenosis as well as peripheral
arterial disease. Despite the growing interest in this lipoprotein, the current
therapeutic options for Lp(a) reduction are limited. Our general approach in
patients with elevated Lp(a) levels is to aggressively manage other modifiable
cardiovascular risk factors including lifestyle modification, consideration of
aspirin therapy, and LDL-C lowering. Unfortunately, there are conflicting reports
on how effective this strategy is at reducing the risk for cardiovascular events
attributed to elevated Lp(a). As a result, targeted Lp(a)-lowering strategies are
needed. Lp(a) therapeutics is an active area of research with several promising
classes of pharmacotherapies under investigation to address this causal
biomarker.
PMID- 28508120
TI - Effects of arm truncation on the appearance of the halo artifact in 68Ga-PSMA-11
(HBED-CC) PET/MRI.
AB - PURPOSE: PSMA ligand imaging with hybrid PET/MRI scanners could be an integral
part of the clinical routine in the future. However, the first study about this
novel method revealed a severe photopenic artifact ("halo artifact") around the
urinary bladder causing significantly reduced tumor visibility. The aim of this
evaluation was to analyze the role of arm truncation on the appearance of the
halo artifact in 68Ga-PSMA-11 PET/MRI hypothesizing that this influences the
appearance. METHODS: Twenty-seven consecutive patients were subjected to 68Ga
PSMA-11 PET/CT (1 h p.i.) followed by PET/MRI (3 h p.i.). PET/MRI was first
started with scans of the abdomen to pelvis with arms positioned up above the
head. Immediately thereafter, additional scans from the pelvis to abdomen were
conducted with arms positioned down beside the trunk. All investigations were
first analyzed separately and then compared with respect to tumor detection and
tumor uptake (SUV) as well as the presence and intensity of the halo artifact.
The Wilcoxon signed rank test was used to determine statistical differences
including Bonferroni correction. RESULTS: The halo was significantly reduced if
the arms were elevated. Lesions inside the halo artifact (n = 16) demonstrated
significantly increased SUVmean (p = 0.0007) and SUVmax (p = 0.0024) with arms
positioned up. The halo appearance and intensity was not dependent on the total
activity and activity concentration of the urinary bladder. CONCLUSION:
Positioning the arms down was shown to be significantly associated with the
appearance of the halo artifact in PET/MRI. Positioning the arms up above the
head can significantly reduce the halo artifact, thereby detecting more tumor
lesions.
PMID- 28508121
TI - Overexpression of SmMYB9b enhances tanshinone concentration in Salvia
miltiorrhiza hairy roots.
AB - KEY MESSAGE: A Salvia miltiorrhiza R2R3-MYB gene, SmMYB9b , has been cloned and
characterized. Overexpression of SmMYB9b resulted in a significant improvement of
tanshinones, the lipophilic active ingredients in danshen hairy roots. Plant R2R3
MYB transcription factors play important roles in various physiological and
biochemical processes. Danshen (Salvia miltiorrhiza bunge) is a valuable
medicinal herb with tanshinones and salvianolic acids as the principal bioactive
ingredients. A number of putative R2R3-MYB transcription factors have been
identified in the plant, but their function remains to be studied. Here, we
report the cloning of SmMYB9b, an S20 R2R3-MYB member and its regulatory
properties. SmMYB9b contains an open reading frame of 792 bp in length and
encodes a 264-amino acid protein. Its transcripts were most abundant in blooming
flowers (except for calyces) and increased with flower development. Exogenous
abscisic acid strongly activated its transcription. Gibberellins and methyl
jasmonate also showed a time-dependent activation effect on its transcription,
but to a weaker degree. Overexpression of SmMYB9b in danshen hairy roots enhanced
tanshinone concentration to 2.16 +/- 0.39 mg/g DW, a 2.2-fold improvement over
the control. In addition to increased tanshinone concentration, the hairy root
growth and lateral hairy root formation were also suppressed. KEGG pathway
enrichment analysis with de novo RNAseq data indicated that stress-response
related metabolic pathways, such as the terpenoid and plant hormone signal
transduction pathways, were significantly enriched, implying possible implication
of SmMYB9b in such processes. Quantitative RT-PCR analysis showed that the
transcription of terpenoid biosynthetic genes SmDXS2, SmDXR, SmGGPPS, and SmKSL1
was significantly up-regulated in danshen hairy roots over expressing SmMYB9b.
These data suggest that overexpression of SmMYB9b results in enhanced tanshinone
concentration through stimulation of the MEP pathway. The present findings shed
new light on elucidating the roles of R2R3-MYB in the biosynthesis of
diterpenoids in S. miltiorrhiza.
PMID- 28508123
TI - Photochemically Controlled Drug Dosing from a Polymeric Scaffold.
AB - PURPOSE: To develop the first photoactive biomaterial coating capable of
controlled drug dosing via inclusion of synthesised drug-3,5-dimethoxybenzoin
(DMB) conjugates in a poly(2-methyoxyethyl acrylate) (pMEA) scaffold. METHODS:
Flurbiprofen- and naproxen-DMB conjugates were prepared via esterification and
characterised via NMR spectroscopy and mass spectrometry following
chromatographic purification. Conjugate photolysis was investigated in
acetonitrile solution and within the pMEA matrix following exposure to low-power
365 nm irradiation. Photo-liberation of drug from pMEA into phosphate buffered
saline was monitored using UV-vis spectroscopy. RESULTS: The synthetic procedures
yielded the desired drug conjugates with full supporting characterisation. Drug
regeneration through photolysis of the synthesised conjugates was successful in
both acetonitrile solution and within the pMEA scaffold upon UV irradiation.
Conjugates were retained within the pMEA scaffold with exclusive drug liberation
following irradiation and increased drug dose with increasing exposure. Multi
dosing capacity was demonstrated though the ability of successive irradiation
periods to generate further bursts of drug. CONCLUSION: This study demonstrates
the first application of photochemically controlled drug release from a
biomaterial coating and the feasibility of using pMEA as a scaffold for housing
the photoactive drug-DMB conjugates.
PMID- 28508122
TI - A Trivalent Enzymatic System for Uricolytic Therapy of HPRT Deficiency and Lesch
Nyhan Disease.
AB - PURPOSE: Because of the evolutionary loss of the uricolytic pathway, humans
accumulate poorly soluble urate as the final product of purine catabolism.
Restoration of uricolysis through enzyme therapy is a promising treatment for
severe hyperuricemia caused by deficiency of hypoxanthine-guanine
phosphoribosyltransferase (HPRT). To this end, we studied the effect of PEG
conjugation on the activity and stability of the enzymatic complement required
for conversion of urate into the more soluble (S)-allantoin. METHODS: We produced
in recombinant form three zebrafish enzymes required in the uricolytic pathway.
We carried out a systematic study of the effect of PEGylation on the function and
stability of the three enzymes by varying PEG length, chemistry and degree of
conjugation. We assayed in vitro the uricolytic activity of the PEGylated
enzymatic triad. RESULTS: We defined conditions that allow PEGylated enzymes to
retain native-like enzymatic activity even after lyophilization or prolonged
storage. A combination of the three enzymes in an appropriate ratio allowed
efficient conversion of urate to (S)-allantoin with no accumulation of
intermediate metabolites. CONCLUSIONS: Pharmaceutical restoration of the
uricolytic pathway is a viable approach for the treatment of severe
hyperuricemia.
PMID- 28508125
TI - Judgement bias in pigs is independent of performance in a spatial holeboard task
and conditional discrimination learning.
AB - Biases in judgement of ambiguous stimuli, as measured in a judgement bias task,
have been proposed as a measure of the valence of affective states in animals. We
recently suggested a list of criteria for behavioural tests of emotion, one of
them stating that responses on the task used to assess emotionality should not be
confounded by, among others, differences in learning capacity, i.e. must not
simply reflect the cognitive capacity of an animal. We performed three
independent studies in which pigs acquired a spatial holeboard task, a free
choice maze which simultaneously assesses working memory and reference memory.
Next, pigs learned a conditional discrimination between auditory stimuli
predicting a large or small reward, a prerequisite for assessment of judgement
bias. Once pigs had acquired the conditional discrimination task, optimistic
responses to previously unheard ambiguous stimuli were measured in the judgement
bias task as choices indicating expectation of the large reward. We found that
optimism in the judgement bias task was independent of all three measures of
learning and memory indicating that the performance is not dependent on the pig's
cognitive abilities. These results support the use of biases in judgement as
proxy indicators of emotional valence in animals.
PMID- 28508126
TI - What's the point? Golden and Labrador retrievers living in kennels do not
understand human pointing gestures.
AB - In many studies that have investigated whether dogs' capacities to understand
human pointing gestures are aspects of evolutionary or developmental social
competences, family-owned dogs have been compared to shelter dogs. However, for
most of these studies, the origins of shelter dogs were unknown. Some shelter
dogs may have lived with families before entering shelters, and from these past
experiences, they may have learned to understand human gestures. Furthermore,
there is substantial variation in the methodology and analytic approaches used in
such studies (e.g. different pointing protocols, different treatment of trials
with no-choice response and indoor vs. outdoor experimental arenas). Such
differences in methodologies and analysis techniques used make it difficult to
compare results obtained from different studies and may account for the divergent
results obtained. We thus attempted to control for several parameters by carrying
out a test on dynamic proximal and distal pointing. We studied eleven kennel dogs
of known origin that were born and raised in a kennels with limited human
interaction. This group was compared to a group of eleven dogs comparable in
terms of breed, sex and age that had lived with human families since they were
puppies. Our results demonstrate that pet dogs outperform kennel dogs in their
comprehension of proximal and distal pointing, regardless of whether trials where
no-choice was made were considered as errors or were excluded from statistical
analysis, meaning that dogs living in kennels do not understand pointing
gestures. Even if genetic effects of the domestication process on human-dog
relationships cannot be considered as negligible, our data suggest that dogs need
to learn human pointing gestures and thus underscore the importance of
ontogenetic processes.
PMID- 28508124
TI - DNA hypermethylation of sFRP5 contributes to indoxyl sulfate-induced renal
fibrosis.
AB - : Renal fibrosis is the most common outcome of chronic kidney disease (CKD),
while the pathogenesis of renal fibrosis is not fully understood. In this study,
we first showed that the progress of renal fibrosis was positively related to
serum levels of indoxyl sulfate, a typical protein-bound toxin, and that there
was a close correlation between serum indoxyl sulfate levels and beta-catenin
expression in the kidneys (r = 0.908, p < 0.001) of CKD patients. We then
demonstrated that intraperitoneal injections of indoxyl sulfate (100 mg/kg/day)
for 4 weeks in uninephrectomized mice explicitly induced renal fibrosis, which
was accompanied by a significant activation of Wnt/beta-catenin signaling. In
vitro investigations in human renal tubular HK-2 cells revealed that indoxyl
sulfate exhibited a potent ability to induce Wnt/beta-catenin activation through
the downregulation of sFRP5, a gene that codes for an extracellular antagonist of
Wnt signaling, by increasing the DNA methylation level of its promoter CpG
islands. The increased expression of DNA methyltransferases following the
activation of ROS/ERK1/2 signaling was responsible for the DNA hypermethylation
of sFRP5 induced by indoxyl sulfate. Conversely, treatment with 5-aza-2'
deoxycytidine, an inhibitor of DNA methyltransferases, significantly reduced
indoxyl sulfate-induced sFRP5 downregulation and Wnt/beta-catenin activation. In
vivo, intraperitoneal injections of recombinant sFRP5 protein or 5-aza-2'
deoxycytidine substantially alleviated renal fibrosis in indoxyl sulfate-treated
uninephrectomized mice. Our results suggest that indoxyl sulfate promotes renal
fibrosis through the induction of DNA hypermethylation of sFRP5, and thereafter
the activation of Wnt/beta-catenin signaling. These findings provide new insights
into the pathogenesis of renal fibrosis in CKD patients. KEY MESSAGES: IS induces
renal fibrosis by increasing beta-catenin expression in CKD mice. IS-induced Wnt
signaling activation is due to sFRP5 hypermethylation in HK-2 cells. ROS/ERK1/2
signaling activation is involved in IS-induced sFRP5 hypermethylation. sFRP5
upregulation attenuates IS-induced renal fibrosis by inhibiting Wnt signaling.
PMID- 28508127
TI - Transcending Landscapes: Working Across Scales and Levels in Pastoralist
Rangeland Governance.
AB - Landscape approaches can be subjected to mistakenly targeting a single "best"
level of governance, and paying too little attention to the role that cross-scale
and cross-level interactions play in governance. In rangeland settings,
resources, patterns of use of those resources, and the institutions for managing
the resources exist at multiple levels and scales. While the scholarship on
commons offers some guidance on how to conceptualize governance in rangeland
landscapes, some elements of commons scholarship-notably the "design principles"
for effective governance of commons-do not seem to apply neatly to governance in
pastoralist rangeland settings. This paper examines three cases where attempts
have been made to foster effective landscape governance in such settings to
consider how the materiality of commons influences the nature of cross-scale and
cross-level interactions, and how these interactions affect governance. In all
three cases, although external actors seemed to work appropriately and
effectively at community and landscape levels, landscape governance mechanisms
have been facing great challenges arising from relationships beyond the
landscape, both vertically to higher levels of decision-making and horizontally
to communities normally residing in other landscapes. The cases demonstrate that
fostering effective landscape-level governance cannot be accomplished only
through action at the landscape level; it is a task that must be pursued at
multiple levels and in relation to the connections across scales and levels. The
paper suggests elements of a conceptual framework for understanding cross-level
and cross-scale elements of landscape governance, and offers suggestions for
governance design in pastoralist rangeland settings.
PMID- 28508129
TI - Development and Characterization of Magnetite/Poly(butylcyanoacrylate)
Nanoparticles for Magnetic Targeted Delivery of Cancer Drugs.
AB - A great attention is presently paid to the design of drug delivery vehicles based
on surface-modified magnetic nanoparticles. They can, in principle, be directed
to a desired target area for releasing their drug payload, a process triggered by
pH, temperature, radiation, or even magnetic field. To this, the possibility of
forming part of diagnostic tools by enhanced magnetic resonance imaging or that
of further treatment by magnetic hyperthermia can be added. Bare particles are
rapidly eliminated from the bloodstream by the phagocyte mononuclear system,
leading to short biological half-life. It is hence required to coat them in order
to increase their biocompatibility and facilitate the drug incorporation. In this
work, magnetite nanoparticles were coated with poly(butylcyanoacrylate) (PBCA)
manufactured and characterized with regard to their physical properties and their
suitability as a platform for magnetically controlled drug delivery. The average
diameter of magnetite and core-shell nanoparticles was 97 +/- 19 and 140 +/- 20
nm, respectively. Infrared analysis, electrophoretic mobility, surface
thermodynamics analysis, and X-ray diffraction all confirmed that the magnetic
particles were sufficiently covered by the polymer in the composite
nanoparticles. In addition, assays using normal (CCD-18 and MCF-10A) and tumoral
(T-84 and MCF-7) cell lines derived from colon and breast tissue, respectively,
demonstrated that nanocomposites have low or negligible cytotoxicity. It is
concluded that PBCA-coated magnetite core-shell nanoparticles represent a
remarkable promise as a platform for magnetically controlled drug delivery.
PMID- 28508128
TI - The cardiothoracic ratio and all-cause and cardiovascular disease mortality in
patients undergoing maintenance hemodialysis: results of the MBD-5D study.
AB - BACKGROUND: The cardiothoracic ratio (CTR) is a non-invasive left ventricular
hypertrophy index. However, whether CTR associates with cardiovascular disease
(CVD) and mortality in hemodialysis (HD) populations is unclear. METHODS: Using a
Mineral and Bone disorder Outcomes Study for Japanese CKD Stage 5D Patients (MBD
5D Study) subcohort, 2266 prevalent HD patients (age 62.8 years, female 38.0%, HD
duration 9.4 years) with secondary hyperparathyroidism (SHPT) whose baseline CTR
had been recorded were selected. We evaluated associations between CTR and all
cause death, CVD death, or composite events in HD patients. RESULTS: CTR was
associated significantly with various background and laboratory characteristics.
All-cause death, CVD-related death, and composite events increased across the CTR
quartiles (Q). Adjusted hazard risk (HR) for all-cause death was 1.4 (95%
confidential interval, 0.9-2.1) in Q2, 1.9 (1.3-2.9) in Q3, and 2.6 (1.7-4.0) in
Q4, respectively (Q1 as a reference). The corresponding adjusted HR for CVD
related death was 1.8 (0.8-4.2), 3.1 (1.4-6.8), and 3.5 (1.6-7.9), and that for
composite outcome was 1.2 (1.0-1.6), 1.7 (1.3-2.2), and 1.8 (1.5-2.3),
respectively. Exploratory analysis revealed that there were relationships
between CTR and age, sex, body mass index, comorbidity of CVD, dialysis duration
and intact parathyroid hormone, phosphorus, hemoglobin, and usage of phosphate
binder [corrected]. CONCLUSION: CTR correlated with all-cause death, CVD death,
and composite events in HD patients with SHPT.
PMID- 28508130
TI - Atmospheric conditions create freeways, detours and tailbacks for migrating
birds.
AB - The extraordinary adaptations of birds to contend with atmospheric conditions
during their migratory flights have captivated ecologists for decades. During the
21st century technological advances have sparked a revival of research into the
influence of weather on migrating birds. Using biologging technology, flight
behaviour is measured across entire flyways, weather radar networks quantify
large-scale migratory fluxes, citizen scientists gather observations of migrant
birds and mechanistic models are used to simulate migration in dynamic aerial
environments. In this review, we first introduce the most relevant microscale,
mesoscale and synoptic scale atmospheric phenomena from the point of view of a
migrating bird. We then provide an overview of the individual responses of
migrant birds (when, where and how to fly) in relation to these phenomena. We
explore the cumulative impact of individual responses to weather during
migration, and the consequences thereof for populations and migratory systems. In
general, individual birds seem to have a much more flexible response to weather
than previously thought, but we also note similarities in migratory behaviour
across taxa. We propose various avenues for future research through which we
expect to derive more fundamental insights into the influence of weather on the
evolution of migratory behaviour and the life-history, population dynamics and
species distributions of migrant birds.
PMID- 28508131
TI - Muscle wasting in chronic kidney disease.
AB - Loss of lean body mass is a relevant component of the cachexia, or protein energy
wasting (PEW), syndrome. Reduced muscle mass seems to be the most solid criterion
for the presence of cachexia/PEW in patients with chronic kidney disease (CKD),
and those with greater muscle mass loss have a higher risk of death. Children
with CKD have many risk factors for lean mass and muscle wasting, including poor
appetite, inflammation, growth hormone resistance, and metabolic acidosis.
Mortality risks in patients with CKD increases as body mass index (BMI) and
weight decreases. However, data regarding cachexia/PEW and muscle wasting in
children with CKD is scarce due to lack of consensus in diagnostic criteria and
an appropriate investigative methodology. Further research is urgently needed to
address this important complication in the pediatric CKD setting, which may have
fundamental impact on clinical outcomes.
PMID- 28508133
TI - Children and Adolescents Macrovascular Reactivity Level and Dynamics, But Not the
Microvascular Response, is Associated with Body Mass Index and Arterial Stiffness
Levels.
AB - INTRODUCTION: The existing evidence indicates that primary prevention of
atherosclerotic disease should begin in childhood. Detection of children and
adolescents at risk for atherosclerosis may allow early intervention to decrease
the atherosclerotic process, thereby preventing or delaying cardiovascular
disease. Vascular reactivity (VR) is altered even by early atherosclerosis.
Obesity is a main cardiovascular risk factor (CVRF) observed in childhood. If
childhood obesity associates impaired macro and/or micro VR is controversial.
AIMS: To characterize macro and micro VR analyzing the stimulus and vascular
response temporal profiles in children and adolescents considering their body
mass index (BMI); and to assess potential associations between subjects'
characteristics and the hyperemic stimulus and/or VR. METHODS: Healthy subjects
(n = 99, age 5-17 years, female 46%) were included. Considering the BMI, normal,
overweight and obese groups were defined. CVRF exposure was assessed. Brachial
flow-mediated dilation and reactive hyperemia, associated with transient ischemia
(forearm cuff-inflation) were evaluated. Diameter, flow velocities, resistive
indexes and shear-stress were determined before, during and after cuff-release.
Complimentary VR indexes were computed. Aortic stiffness and aortic and brachial
blood pressure were determined. RESULTS: Obese showed the lowest and slowest
macrovascular response (p < 0.05). Micro VR was not associated with obesity.
Higher aortic stiffness levels were associated with slower macrovascular
responses (p < 0.05). CONCLUSION: Childhood obesity associates not only reduced,
but also slowed macrovascular reactivity. Microvascular response to transient
ischemia is preserved in obese children. Macro and microvascular responses would
be non-associated phenomena in childhood. During childhood, VR dynamics would
depend on the arterial stiffness.
PMID- 28508132
TI - Survival in children requiring chronic renal replacement therapy.
AB - Survival in the pediatric end-stage renal disease (ESRD) population has improved
substantially over recent decades. Nonetheless, mortality remains at least 30
times higher than that of healthy peers. Patient survival is multifactorial and
dependent on various patient and treatment characteristics and degree of economic
welfare of the country in which a patient is treated. In this educational review,
we aim to delineate current evidence regarding mortality risk in the pediatric
ESRD population and provide pediatric nephrologists with up-to-date information
required to counsel affected families.
PMID- 28508134
TI - Effect of Combat Stress in the Psychophysiological Response of Elite and Non
Elite Soldiers.
AB - We aimed to analyse the effect of combat stress in the psychophysiological
responses of elite and non-elite soldiers. We analysed heart rate, cortical
arousal, skin temperature, blood lactate concentration and lower body muscular
strength before and after a tactical combat simulation in 40 warfighters divided
in two groups: elite (n: 20; 28.5 +/- 6.38 years) and non-elite (n:20; 31.94 +/-
6.24 years) group. Elite presented a significantly higher lactate concentration
after combat than non elite soldiers (3.8 +/- 1.5 vs 6.6 +/- 1.3 mmol/L). Non
elite soldiers had a higher heart rate pre and post the simulation than elite
(82.9 +/- 12.3 vs 64.4 +/- 11. pre non elite and elite respectively; 93.0 +/-
12.8 vs 88 +/- 13.8 bpm post non elite and elite respectively). Elite soldiers
presented higher lower muscular strength than elite in all test and before and
after the combat simulation. Cortical arousal was not modified significantly in
both groups. We conclude elite soldiers presented in combat a higher anaerobic
metabolism activation and muscular strength than non-elite soldiers, but
cardiovascular, cortical, and muscular strength manifestation presented the same
response in both elite and non-elite soldiers.
PMID- 28508136
TI - A fixed correction of absolute transpulmonary pressure may not be ideal for
clinical use : Discussion on "Accuracy of esophageal pressure to assess
transpulmonary pressure during mechanical ventilation".
PMID- 28508137
TI - The fractal lightning burn results from a positively charged strike : Discussion
on "Resuscitated unconscious male: Lichtenberg's sign lighting the way".
PMID- 28508138
TI - Prevalence and Risk Factors Associated with Forced-Sex Among South African High
School Students.
AB - Sexual violence, a global concern, has far reaching consequences for individuals
and communities. This survey of South African high school students, reported
baseline prevalence and factors associated with forced sex. Data collected among
434 adolescents (54.4% boys; 45.6% girls) used a questionnaire developed using
the I-Change Model conceptual framework. Forced sex prevalence was 14.2% (95% CI
9.1, 21.5) with a non-significant difference between females (15.0%) and males
(13.6%) (p = 0.781). After multivariable adjustment, urban location (39%), low
socio-economic status (15%) and discordant mother/father vital status (20%)
remained significant risk factors for forced sex. South African high school
students are still at risk of experiencing forced sex with a higher prevalence in
females. Interventions to address socio-economic and structural constructs
contributing to the forced sex prevalence in this population are required.
PMID- 28508135
TI - Adaptations of archaeal and bacterial membranes to variations in temperature, pH
and pressure.
AB - The cytoplasmic membrane of a prokaryotic cell consists of a lipid bilayer or a
monolayer that shields the cellular content from the environment. In addition,
the membrane contains proteins that are responsible for transport of proteins and
metabolites as well as for signalling and energy transduction. Maintenance of the
functionality of the membrane during changing environmental conditions relies on
the cell's potential to rapidly adjust the lipid composition of its membrane.
Despite the fundamental chemical differences between bacterial ester lipids and
archaeal ether lipids, both types are functional under a wide range of
environmental conditions. We here provide an overview of archaeal and bacterial
strategies of changing the lipid compositions of their membranes. Some molecular
adjustments are unique for archaea or bacteria, whereas others are shared between
the two domains. Strikingly, shared adjustments were predominantly observed near
the growth boundaries of bacteria. Here, we demonstrate that the presence of
membrane spanning ether-lipids and methyl branches shows a striking relationship
with the growth boundaries of archaea and bacteria.
PMID- 28508139
TI - Functional annotation of a novel toxin-antitoxin system Xn-RelT of Xenorhabdus
nematophila; a combined in silico and in vitro approach.
AB - Toxin-antitoxin (TA) complexes play an important role in stress responses and
programmed cell death in bacteria. The RelB-RelE toxin antitoxin system is well
studied in Escherichia coli. In this study, we used combined in silico and in
vitro approaches to study a novel Xn-RelT toxin from Xenorhabdus nematophila
bearing its own antitoxin Xn-RelAT-a RelB homolog of E. coli. The structure for
this toxin-antitoxin pair is yet unknown. We generated homology-based models of
X. nematophila RelT toxin and antitoxin. The deduced models were further
characterized for protein-nucleic acid, protein-protein interactions and gene
ontology. A detrimental effect of recombinant Xn-RelT on host E. coli was
determined through endogenous toxicity assay. When expressed from a isopropyl
beta-D-1-thiogalactopyranoside-regulated LacZ promoter, Xn-RelT toxin showed a
toxic effect on E. coli cells. These observations imply that the conditional
cooperativity governing the Xn-RelT TA operon in X. nematophila plays an
important role in stress management and programmed cell death.
PMID- 28508140
TI - The State and Future of the Primary Care Behavioral Health Model of Service
Delivery Workforce.
AB - The growth of the Primary Care Behavioral Health model (PCBH) nationally has
highlighted and created a workforce development challenge given that most mental
health professionals are not trained for primary care specialization. This work
provides a review of the current efforts to retrain mental health professionals
to fulfill roles as Behavioral Health Consultants (BHCs) including certificate
programs, technical assistance programs, literature and on-the-job training, as
well as detail the future needs of the workforce if the model is to sustainably
proliferate. Eight recommendations are offered including: (1) the development of
an interprofessional certification body for PCBH training criteria, (2)
integration of PCBH model specific curricula in graduate studies, (3) integration
of program development skill building in curricula, (4) efforts to develop
faculty for PCBH model awareness, (5) intentional efforts to draw students to
graduate programs for PCBH model training, (6) a national employment
clearinghouse, (7) efforts to coalesce current knowledge around the provision of
technical assistance to sites, and (8) workforce specific research efforts.
PMID- 28508141
TI - Relationships Between Traumatic Life Events, Cognitive Emotion Regulation
Strategies, and Somatic Complaints.
AB - The aim of this study was to investigate the relationships between traumatic life
events, specific cognitive emotion regulation strategies, and present somatic
complaints. The sample consisted of 465 adults from the general population. The
participants filled in online self-report questionnaires with regard to somatic
complaints (SCL-90), cognitive emotion regulation strategies (CERQ) and traumatic
life events. Multiple regression analysis was performed to study the
relationships. The results showed that present somatic complaints were
significantly related to the reporting of past negative events (such as loss and
maltreatment) that still produce strong and negative feelings in the present.
Somatic complaints were also significantly related to a more frequent use of
maladaptive cognitive coping strategies, such as blaming oneself, ruminating, and
catastrophizing about negative life events. Inquiring about unresolved traumatic
memories and coping strategies can help guide a clinicians' approach to managing
patients with somatic complaints that have no clear medical explanation.
PMID- 28508142
TI - When Is It Better to Wait? Surgical Timing and Recurrence Risk for Children
Undergoing Repair of Subaortic Stenosis.
AB - Recurrence of subaortic stenosis (SAS) after surgery is common in children. The
effects of patient characteristics and surgical timing on disease recurrence are
largely unknown. We performed a retrospective study, assessing the relative
effects of patient age and left ventricular outflow tract (LVOT) gradient on the
need for reoperation for recurrent SAS. We included all children <20 years of age
who underwent initial surgical resection of SAS at our center, January 2003
December 2013. Stratified logistic regression was performed, considering the
effects of patient demographics, clinical characteristics, echocardiographic
parameters, and operative technique, and clustering standard errors by surgeon.
The multivariable model was used to simulate predicted probabilities of recurrent
SAS for children at varying ages and baseline LVOT gradients. Sixty-three
patients (38 males) underwent initial operation for SAS. Patients were followed
for a median of 3.7 years (IQR 1.2-7.1). Twenty-one percent of patients (n = 13)
underwent reoperation for SAS. Twelve were male. For every 10 mmHg increase in
preoperative peak gradient in boys, the odds of reoperation for SAS doubled (OR
2.01, CI 1.5-2.72, p < 0.001), and for every additional 6 months of age, the odds
of reoperation decreased by 14% (OR 0.86, CI 0.84-0.88, p < 0.001). Both younger
age and higher preoperative outflow tract gradient are independently associated
with risk of reoperation. Clinicians should consider the age and rate of LVOT
gradient change-and not just the absolute gradient-in determining initial
surgical timing.
PMID- 28508143
TI - Great tit response to decreasing industrial heavy metal emissions.
AB - This study evaluated the effects of environmental pollution on decreasing great
tit (Parus major) breeding parameters in an industrial area in the west coast of
Portugal. Several great tit breeding parameters were monitored in the industrial
area, as well as in a rural area not affected by industrial emissions. Low levels
of air pollution in both industrial and rural areas were confirmed by assessing
trace element concentrations in pine needles. Concentrations of Cd and Hg in pine
needles from the industrial area (Cd = 0.05 ppm; Hg = 0.005 ppm) were
significantly lower than those found in needles collected from the reference area
(Cd = 0.07 ppm; Hg = 0.007 ppm). Additionally, the breeding success of great tits
increased in the industrial area in comparison to the reference area (0.93 +/-
0.08 and 0.62 +/- 0.22, respectively). The changes on great tit breeding
parameters were probably related with changes in the breeding density of other
competitive species, together with a decreasing frass-fall biomass. Further long
term ecological studies in industrial areas are necessary to understand the
changing breeding performance and strategies used by great tits in response to
pollution shifts in the environment.
PMID- 28508144
TI - Radical Lymph Node Dissection Along the Proximal Splenic Artery During
Laparoscopic Gastrectomy for Gastric Cancer Using the Left Lateral Approach.
AB - BACKGROUND: Recent technical improvements allow safe laparoscopic lymph node
dissection (LND) in gastric cancer.1 , 2 In suprapancreatic LND, careful LND
around the celiac artery (CA) is essential. From a patient's right side, deep LND
is performed around the right side of the CA after dissecting around the common
hepatic artery (CHA). For LND around the left side of the CA on the same
operative axis as the right side, we developed a new procedure for LND along the
proximal splenic artery (SA), performed from the patient's left side. METHODS:
After LND around the CHA and right side of the CA from the patient's right side,
the surgeon then moves to the patient's left side. The anterior pancreatic fascia
is cut at the middle point of the SA to discern the dorsal layer of the LN along
the SA, such as the splenic vein. LND is performed by preserving the posterior
pancreatic fascia around the SA in a left-to-right direction. Finally, the LNs
around the left side of the CA are deeply dissected. RESULTS: We performed this
procedure on ten patients between April 2016 and January 2017; no operative
complications were reported in grade II or higher cancer patients.3 After
exposing the dorsal landmark, LNs around the proximal SA and left side of the CA
were removed in all patients. CONCLUSION: This procedure enables early
identification of the dorsal layer and deep LND around the left side of the CA,
keeping this layer. The left lateral approach is useful for radical LND along the
proximal SA.
PMID- 28508145
TI - Sentinel Lymph Node Biopsy for Recurrent Melanoma: A Multicenter Study.
AB - BACKGROUND: Sentinel lymph node biopsy (SLNB) is routinely performed for primary
cutaneous melanomas; however, limited data exist for SLNB after locally recurrent
(LR) or in-transit (IT) melanoma. METHODS: Data from three centers performing
SLNB for LR/IT melanoma (1997 to the present) were reviewed, with the aim of
assessing (1) success rate; (2) SLNB positivity; and (3) prognostic value of SLNB
in this population. RESULTS: The study cohort included 107 patients. Management
of the primary melanoma included prior SLNB for 56 patients (52%), of whom 10
(18%) were positive and 12 had complete lymph node dissections (CLNDs). In the
present study, SLNB was performed for IT disease (48/107, 45%) or LR melanoma
(59/107, 55%). A sentinel lymph node (SLN) was removed in 96% (103/107) of cases.
Nodes were not removed for four patients due to lymphoscintigraphy failures (2)
or nodes not found during surgery (2). SLNB was positive in 41 patients (40%, 95%
confidence interval (CI) 31.5-50.5), of whom 35 (88%) had CLND, with 13 (37%)
having positive nonsentinel nodes. Median time to disease progression after LR/IT
metastasis was 1.4 years (95% CI 0.75-2.0) for patients with a positive SLNB, and
5.9 years (95% CI 1.7-10.2) in SLNB-negative patients (p = 0.18). There was a
trend towards improved overall survival for patients with a negative SLNB (p =
0.06). CONCLUSION: SLNB can be successful in patients with LR/IT melanoma, even
if prior SLNB was performed. In this population, the rates of SLNB positivity and
nonsentinel node metastases were 40% and 37%, respectively. SLNB may guide
management and prognosis after LR/IT disease.
PMID- 28508146
TI - Laparoscopic Parenchymal-Sparing Liver Resections Using the Intrahepatic
Glissonian Approach.
AB - BACKGROUND: One of the main criticisms of laparoscopic liver resection is that it
is difficult, or not possible, to perform liver-sparing resections. Our aim was
to present short videos where the intrahepatic Glissonian approach was used to
perform anatomical liver segmental resections, instead of a larger operation, to
avoid unnecessary sacrifice of the liver parenchyma. METHODS: We selected six
types of anatomical liver resections to exemplify the use of the intrahepatic
Glissonian approach to perform segment-oriented liver resections. These types of
hepatectomies were used as an alternative to right or left hepatectomy, or as an
alternative to extended liver resections. RESULTS: The intrahepatic Glissonian
approach was feasible in all cases. The use of anatomical landmarks previously
described was essential to reach and control the Glissonian pedicles. Among the
liver-sparing resections, we were able to perform right anterior (S5 + S8) and
posterior (S6 + S7) sectionectomies, resection of segments 2, 3, and 4, and
mesohepatectomy (S4 + S5 + S8). No patient presented postoperative liver failure.
CONCLUSIONS: Laparoscopic liver-sparing resections are feasible and may be a good
alternative to hemihepatectomies or extended liver resections. The use of the
intrahepatic Glissonian approach can be useful.
PMID- 28508147
TI - Identification of beta-Lactamases and beta-Lactam-Related Proteins in Human
Pathogenic Bacteria using a Computational Search Approach.
AB - A systematic analysis of beta-lactamases based on comparative proteomics has not
been performed thus far. In this report, we searched for the presence of beta
lactam-related proteins in 591 bacterial proteomes belonging to 52 species that
are pathogenic to humans. The amino acid sequences for 19 different types of beta
lactamases (ACT, CARB, CifA, CMY, CTX, FOX, GES, GOB, IMP, IND, KPC, LEN, OKP,
OXA, OXY, SHV, TEM, NDM, and VIM) were obtained from the ARG-ANNOT database and
were used to construct 19 HMM profiles, which were used to identify potential
beta-lactamases in the completely sequenced bacterial proteomes. A total of 2877
matches that included the word "beta-lactamase" and/or "penicillin" in the
functional annotation and/or in any of its regions were obtained. These enzymes
were mainly described as "penicillin-binding proteins," "beta-lactamases," and
"metallo-beta-lactamases" and were observed in 47 of the 52 species studied. In
addition, proteins classified as "beta-lactamases" were observed in 39 of the
species included. A positive correlation between the number of beta-lactam
related proteins per species and the proteome size was observed (R 0.78, P <
0.00001). This correlation partially explains the high presence of beta-lactam
related proteins in large proteomes, such as Nocardia brasiliensis, Bacillus
anthracis, and Mycobacterium tuberculosis, along with their absence in small
proteomes, such as Chlamydia spp. and Mycoplasma spp. We detected only five types
of beta-lactamases (TEM, SHV, CTX, IMP, and OXA) and other related proteins in
particular species that corresponded with those reported in the literature. We
additionally detected other potential species-specific beta-lactamases that have
not yet been reported. In the future, better results will be achieved due to more
accurate sequence annotations and a greater number of sequenced genomes.
PMID- 28508148
TI - Thermographic skin temperature measurement compared with cold sensation in
predicting the efficacy and distribution of epidural anesthesia.
AB - Due to the high rates of epidural failure (3-32%), novel techniques are required
to objectively assess the successfulness of an epidural block. In this study we
therefore investigated whether thermographic temperature measurements have a
higher predictive value for a successful epidural block when compared to the cold
sensation test as gold standard. Epidural anesthesia was induced in 61 patients
undergoing elective abdominal, thoracic or orthopedic surgery. A thermographic
picture was recorded at 5, 10 and 15 min following epidural anesthesia induction.
After 15 min a cold sensation test was performed. Epidural anesthesia is
associated with a decrease in skin temperature. Thermography predicts a
successful epidural block with a sensitivity of 54% and a PPV of 92% and a
specificity of 67% and a NPV of 17%. The cold sensation test shows a higher
sensitivity and PPV than thermography (97 and 93%), but a lower specificity and
NPV than thermography (25 and 50%). Thermographic temperature measurements can be
used as an additional and objective method for the assessment of the
effectiveness of an epidural block next to the cold sensation test, but have a
low sensitivity and negative predictive value. The local decrease in temperature
as observed in our study during epidural anesthesia is mainly attributed to a
core-to-peripheral redistribution of body heat and vasodilation.
PMID- 28508149
TI - Parkinson's Disease-Associated Mutant LRRK2-Mediated Inhibition of miRNA Activity
is Antagonized by TRIM32.
AB - Parkinson's disease (PD) is the second most common neurodegenerative disorder.
Accumulating evidences suggest that PD might have a strong neurodevelopmental
component. Among the genetic cases, mutations in the leucine-rich repeat kinase 2
(LRRK2) are well known to be disease causing. Although the molecular mechanism of
the pathogenic LRRK2 function is not fully clear, inhibition of microRNA (miRNA)
activity has been suggested to be among the pathogenic LRRK2 targets. Here, we
demonstrate that the miRNA activity inhibition function of pathogenic LRRK2 is
directly antagonized by the neuronal cell fate determinant TRIM32. These findings
suggest that TRIM32 might be a modifier for PD and could be a novel therapeutic
target.
PMID- 28508150
TI - Exogenous BDNF Increases Mitochondrial pCREB and Alleviates Neuronal Metabolic
Defects Following Mechanical Injury in a MPTP-Dependent Way.
AB - Metabolic defects are common pathological phenomena following traumatic brain
injury (TBI) which contribute to poor prognosis. Brain-derived neurotrophic
factor (BDNF) is an important regulator of neuronal survival, development,
function, and plasticity. This study was designed to investigate the potential
effects of BDNF on TBI-induced metabolic defects and their underlying molecular
mechanisms. BDNF was added into cultured neurons to a concentration of 25, 50,
and 100 ng/ml, respectively, right after mechanical injury and metabolite levels
were analyzed 4 h post injury. The mitochondrial phosphorylated cAMP response
element-binding protein (pCREB) distribution and complex V synthesis, as well as
their roles in metabolic defects, were evaluated. We found that exogenous BDNF
improved metabolic defects, especially the uncoupling of oxidative
phosphorylation. BDNF increased pCREB in mitochondrial inner membrane and matrix
and promoted mitochondrial complex V synthesis. We also found that these results
were negatively regulated by the mitochondrial permeability transition pore
(MPTP) antagonist CsA and positively regulated by the MPTP agonist atractyloside.
BDNF's protectional effects on metabolic defects were abolished by CREB knockout.
When administrated in a dominant interfering CREB mutant (A-CREB) model,
mitochondrial pCREB accumulation could still be observed, but the synthesis of
complex V and alleviation of metabolic defects were repressed. Our data
demonstrate that exogenous BDNF mitigates neuronal metabolic defects following
mechanical injury by promoting the pCREB accumulation in mitochondrial inner
membrane and matrix, which is regulated by MPTP opening, thus facilitating the
synthesis of mitochondrial complex V.
PMID- 28508151
TI - Tunable and Nontoxic Fluorescent Probes Based on Carbon Dots for Imaging of
Indole Propionic Acid Receptor in Plant Tissues in Situ.
AB - Indole propionic acid (IPA) is one of the important plant growth hormones for
promoting rooting and fruiting. Labeling IPA receptor in plant tissues is able to
further track the signal transduction processes of IPA and uncover the function
mechanism of IPA on crop productions. In this paper, a tunable and nontoxic
fluorescent probe for IPA receptors was designed and synthetized base on carbon
dots (C dots). Firstly carboxyl-modified carbon dots were prepared by high
temperature cracking of citric acid. The fluorescence emission wavelengths of C
dots varied with the excitation wavelengths change. Then IPA-modified carbon dots
(IPA-C dots) were prepared by coupling the amino of tryptophan with the carboxyl
of as-prepared carbon dots. Compared with C dots, the fluorescence intensity of
IPA-C dots was double and the fluorescence stability was satisfactory under
various conditions. This probe retained the biological activity of IPA and acted
as target recognition of IPA receptors in plant tissues. The probe could avoid
green fluorescence background of plants. The imaging results showed that the IPA
receptors mainly existed on the membrane of stele. The toxicity test indicated
the probe was less toxic than traditional inorganic semiconductor quantum dots.
PMID- 28508152
TI - Detection of HER2 Amplification in Circulating Tumor Cells of HER2-Negative
Gastric Cancer Patients.
AB - A key to the successful use of targeted cancer therapy is the ability to
preselect patients who are likely to benefit from the treatment according to
molecular markers. Assessment for predicting therapy response is mostly done
using tumor biopsies. However, these might not truly represent all of the
patient's malignant cells because of tumor heterogeneity and/or clonal evolution
during disease progression. One potential strategy that can complement primary
tumor biopsy is the analysis of circulating tumor cells (CTCs). In this study, we
analyzed CTCs of patients with gastric cancer (GC) to find those who were likely
to benefit from trastuzumab therapies. We developed an imaging-based method that
enabled CTC identification simultaneously with evaluation of HER2 gene
amplification (the 3D-IF-FISH method). Then we performed a study enrolling 101 GC
patients in whom we analyzed CTCs by both 3D-IF-FISH and an FDA-approved
CellSearch system. As compared with the CellSearch system, 3D-IF-FISH methods
identified a higher number of patients whose primary tumors were HER2- but who
had HER2+ CTCs, suggesting that the 3D-IF-FISH method is effective in
preselecting patients for trastuzumab therapies. To demonstrate this, we
performed an exploratory clinical study to evaluate the clinical benefits of
trastuzumab treatment for advanced GC patients (n = 15) whose primary tumors were
HER2-, but whose CTCs showed HER2 amplification. An interim evaluation after the
first stage showed that these preselected patients had response rates comparable
to those reported in the trastuzumab-plus-chemotherapy arm of the ToGA study. The
present study offers a new, non-invasive strategy to select patients who are
likely to benefit from trastuzumab-based therapies, despite their primary biopsy
being HER2-negative. (UMIN ID: UMIN000008622).
PMID- 28508154
TI - Estimating Loss of Brucella Abortus Antibodies from Age-Specific Serological Data
In Elk.
AB - Serological data are one of the primary sources of information for disease
monitoring in wildlife. However, the duration of the seropositive status of
exposed individuals is almost always unknown for many free-ranging host species.
Directly estimating rates of antibody loss typically requires difficult
longitudinal sampling of individuals following seroconversion. Instead, we
propose a Bayesian statistical approach linking age and serological data to a
mechanistic epidemiological model to infer brucellosis infection, the probability
of antibody loss, and recovery rates of elk (Cervus canadensis) in the Greater
Yellowstone Ecosystem. We found that seroprevalence declined above the age of
ten, with no evidence of disease-induced mortality. The probability of antibody
loss was estimated to be 0.70 per year after a five-year period of seropositivity
and the basic reproduction number for brucellosis to 2.13. Our results suggest
that individuals are unlikely to become re-infected because models with this
mechanism were unable to reproduce a significant decline in seroprevalence in
older individuals. This study highlights the possible implications of antibody
loss, which could bias our estimation of critical epidemiological parameters for
wildlife disease management based on serological data.
PMID- 28508153
TI - Cellular and molecular perspectives in rheumatoid arthritis.
AB - Synovial immunopathology in rheumatoid arthritis is complex involving both
resident and infiltrating cells. The synovial tissue undergoes significant
neovascularization, facilitating an influx of lymphocytes and monocytes that
transform a typically acellular loose areolar membrane into an invasive tumour
like pannus. The microvasculature proliferates to form straight regularly
branching vessels; however, they are highly dysfunctional resulting in reduced
oxygen supply and a hypoxic microenvironment. Autoantibodies such as rheumatoid
factor and anti-citrullinated protein antibodies are found at an early stage,
often before arthritis has developed, and they have been implicated in the
pathogenesis of RA. Abnormal cellular metabolism and mitochondrial dysfunction
thus ensue and, in turn, through the increased production of reactive oxygen
species actively induce inflammation. Key pro-inflammatory cytokines, chemokines
and growth factors and their signalling pathways, including nuclear factor
kappaB, Janus kinase-signal transducer, are highly activated when immune cells
are exposed to hypoxia in the inflamed rheumatoid joint show adaptive survival
reactions by activating. This review attempts to highlight those aberrations in
the innate and adaptive immune systems including the role of genetic and
environmental factors, autoantibodies, cellular alterations, signalling pathways
and metabolism that are implicated in the pathogenesis of RA and may therefore
provide an opportunity for therapeutic intervention.
PMID- 28508156
TI - Pulse wave velocity measurement as a marker of arterial stiffness in pediatric
inflammatory bowel disease: a pilot study.
AB - : In adults with inflammatory bowel disease (IBD), the incidence of
cardiovascular events is increased, leading to long-term morbidity. Arterial
stiffness (AS) measured by pulse wave velocity (PWV) is a validated early
precursor of cardiovascular disease (CVD), and measurement of PWV was shown to be
a feasible test in children. The aim of this study was to assess AS in children
with IBD. In this prospective study, we determined PWV between the carotid and
femoral artery (PWVcf) in 25 children and adolescents with IBD (11 females,
median age 14.1 years, median disease duration 2.8 years). The majority (68%) of
the subjects were in clinical remission, and 48% received anti-tumor necrosis
factor alpha (TNFalpha) treatment. AS was not increased in this cohort of
children and adolescents with IBD, who did not have signs of cardiovascular
disease, such as arterial hypertension. CONCLUSION: PWV seems to be normal in
children with IBD in remission or with mild disease activity. Larger studies
should assess its potential role as a valid and non-invasive follow-up marker in
children with IBD, to avoid cardiovascular complications. What is Known : *
Inflammatory bowel disease (IBD) is a risk factor of cardiovascular disease
(CVD). * Pulse wave velocity (PWV) measurement is the current gold standard to
assess arterial stiffness (AS), which is an early predictor of CVD. What is New:
* This is the first study using PWV measurements to determine AS in children with
IBD. * In children with IBD in remission or only mild disease activity AS is not
increased.
PMID- 28508155
TI - Retention of South African Adolescents in a 54-Month Longitudinal HIV Risk
Reduction Trial.
AB - Retention of participants in clinical trials is a central concern of HIV/STI
behavioral researchers and research sponsors. This article describes the
strategies used for addressing the challenges in retaining South African
adolescents for a 54-month longitudinal study. The objective of the South African
adolescent health promotion long-term follow-up trial was to test the
sustainability of the effects of an HIV/STI risk reduction intervention, "Let Us
Protect Our Future," on young adolescents as they aged into middle and late
adolescence. Inaccurate contact information, invalid mobile telephone numbers,
lack of transportation, transitory family addresses, and family relocation were
among the challenges to retaining participants. Despite a significant gap in time
of 36 months between the main trial and the long-term follow-up study, 99.2% of
1057 participants were retained. Solutions used for retaining the adolescents are
discussed with suggestions offered for retaining adolescents in longitudinal
HIV/STI prevention clinical trials in low resource countries.
PMID- 28508157
TI - Integument cell gelatinisation-the fate of the integumentary cells in Hieracium
and Pilosella (Asteraceae).
AB - Members of the genera Hieracium and Pilosella are model plants that are used to
study the mechanisms of apomixis. In order to have a proper understanding of
apomixis, knowledge about the relationship between the maternal tissue and the
gametophyte is needed. In the genus Pilosella, previous authors have described
the specific process of the "liquefaction" of the integument cells that surround
the embryo sac. However, these observations were based on data only at the light
microscopy level. The main aim of our paper was to investigate the changes in the
integument cells at the ultrastructural level in Pilosella officinarum and
Hieracium alpinum. We found that the integument peri-endothelial zone in both
species consisted of mucilage cells. The mucilage was deposited as a thick layer
between the plasma membrane and the cell wall. The mucilage pushed the protoplast
to the centre of the cell, and cytoplasmic bridges connected the protoplast to
the plasmodesmata through the mucilage layers. Moreover, an elongation of the
plasmodesmata was observed in the mucilage cells. The protoplasts had an
irregular shape and were finally degenerated. After the cell wall breakdown of
the mucilage cells, lysigenous cavities that were filled with mucilage were
formed.
PMID- 28508158
TI - How I do it: surgical ligation of craniocervical junction dural AV fistulas.
AB - BACKGROUND: Dural arteriovenous fistulas (DAVFs) of the craniocervical junction
are uncommon vascular lesions, which often require surgical treatment even in the
endovascular era. METHODS: Most commonly, the fistula is placed laterally, and
surgical ligation is performed through a lateral suboccipital craniotomy. After
dural opening, the area is inspected, and the arterialized vein is identified
emerging from the dura, often adjacent to the entry point of the vertebral
artery, and ligated. CONCLUSIONS: A far lateral craniotomy is the authors'
preferred surgical approach for accessing and treating dural arteriovenous
fistulas of the craniocervical junction that cannot be reached endovascularly.
PMID- 28508159
TI - Constant dripping wears away the bone: intraosseous C2 and suboccipital
intradiploic cerebrospinal fluid collection after Chiari I decompressive surgery.
AB - The objective of decompressive surgery for Chiari I malformation is to create
additional space to accommodate the ectopic cerebellar tonsils and to improve the
flow of cerebrospinal fluid. To the best of our knowledge, we report the first
case of a patient with previous Chiari I decompression presenting 5 years after
surgery at the same time as an intraosseous C2 and a suboccipital intradiploic
cerebrospinal fluid accumulation. Because of the progressive nature of the C2
cerebrospinal fluid collection causing bone destruction, surgical management was
indicated. To avoid the erosion of the bone, we propose that the iatrogenic
exposure of the diploe and the vertebral spongiosa that may come into contact
with the cerebrospinal fluid should be sealed off with bone wax or a similar
material.
PMID- 28508160
TI - Operative simulation of anterior clinoidectomy using a rapid prototyping model
molded by a three-dimensional printer.
AB - BACKGROUND: As the anatomical three-dimensional (3D) positional relationship
around the anterior clinoid process (ACP) is complex, experience of many
surgeries is necessary to understand anterior clinoidectomy (AC). We prepared a
3D synthetic image from computed tomographic angiography (CTA) and magnetic
resonance imaging (MRI) data and a rapid prototyping (RP) model from the imaging
data using a 3D printer. The objective of this study was to evaluate anatomical
reproduction of the 3D synthetic image and intraosseous region after AC in the RP
model. In addition, the usefulness of the RP model for operative simulation was
investigated. METHODS: The subjects were 51 patients who were examined by CTA and
MRI before surgery. The size of the ACP, thickness and length of the optic nerve
and artery, and intraosseous length after AC were measured in the 3D synthetic
image and RP model, and reproducibility in the RP model was evaluated. In
addition, 10 neurosurgeons performed AC in the completed RP models to investigate
their usefulness for operative simulation. RESULTS: The RP model reproduced the
region in the vicinity of the ACP in the 3D synthetic image, including the
intraosseous region, at a high accuracy. In addition, drilling of the RP model
was a useful operative simulation method of AC. CONCLUSIONS: The RP model of the
vicinity of ACP, prepared using a 3D printer, showed favorable anatomical
reproducibility, including reproduction of the intraosseous region. In addition,
it was concluded that this RP model is useful as a surgical education tool for
drilling.
PMID- 28508162
TI - First report of oestrosis in aoudad from southeastern Spain.
AB - In spring 2016, we analyzed the skull of 44 aoudads (Ammotragus lervia) from
Sierra Espuna Regional Park (SE Spain) for the presence of oestrid larvae.
Oestrus ovis larvae were found in 27.3% of sampled hosts, with a mean intensity
of 1.5 +/- 6.1 larvae/per parasitized host (range 1-21). To our knowledge, this
is the first report of oestrosis affecting this host species.
PMID- 28508163
TI - Development of molecular diagnostic protocols for detecting three types of
Entamoeba from diarrheal and asymptomatic pigs and environmental moist soils.
AB - Entamoeba suis and Entamoeba polecki subtypes (ST) 1 and 3 have recently been
implicated in disease outbreaks in pigs. However, the distributions of these
parasites in Japan and the potential sources of infection on farms still remain
unclear. Here, we examined a farm of fattening/growing pigs with abnormal feces
in Kagoshima Prefecture, Japan, and found the presence of parasites in the farm
environment. Examination of intestinal tissues from pigs presenting with
ulcerative colitis revealed a large number of trophozoites that had invaded the
lesions. We identified single and mixed infections of E. suis and E. polecki ST1
and ST3 in paraffin sections or fecal samples from affected pigs. Two subtypes of
Entamoeba were identified using four primer sets by PCR and sequencing. The
parasites were detected in moist soil samples obtained around the drinking water
source or puddles, implicating transmission of cysts via contaminated soils.
Additionally, we found evidence of Entamoeba spp. and coinfections in surveyed
pigs without any diarrhea at two neighboring farms. Our results establish methods
for successfully identification of parasites, including cases in which multiple
infections are present.
PMID- 28508164
TI - Viability of Strongyloides venezuelensis eggs and larvae in vermiculite
containing the fungus Duddingtonia flagrans.
AB - Strongyloidiasis is the most clinically important disease among the infections
caused by geohelminths, seeing that this parasite can cause autoinfection. The
use of nematophagous fungi like Duddingtonia flagrans, that have predation action
on eggs and infecciososas forms of helminths, emerges as an alternative method
for environmental control. For this reason, analyzing the viability of larvae and
eggs of Strongyloides venezuelensis and the action of Duddingtonia flagrans AC001
in vermiculite, as well as the action of the nematophagous fungi in different
growth stages, is important to elaborate and define the best culture conditions
that favor the activity of the fungus. Two different growth conditions were
applied: both eggs and AC001 fungi were added at the same time to the vermiculite
(assay A) and the addition of eggs after the growth of the AC001 fungi in the
vermiculite (assay B). To recover the L3 larvae, the Baermann-Moraes method was
applied, followed by the counting of L3 dead and alive. At last, it was observed
that the vermiculite enriched with organic material is an adequate culture medium
not only for the growth of the S. venezuelensis but also for the growth of the D.
flagrans fungus, being therefore, a satisfactory culture medium for tests of
viability and predatory action of this fungus. It was also observed that the
activity of the AC001 fungus is greater when it is growing concomitantly with the
eggs, in other words, when it is in the adaptation phase.
PMID- 28508165
TI - Frequency of Toxoplasma gondii in the retina in eye banks in Brazil.
AB - Ocular toxoplasmosis is the main cause of posterior uveitis worldwide frequently
leading to vision loss. In Brazil, the seroprevalence of Toxoplasma gondii
infection ranges from 50 to 80% depending of the region studied. The frequency of
toxoplasmic retinal scar may reach 18% of the adults in the South of Brazil. Our
goal was to determine the frequency of T. gondii DNA in retinas from eye banks
from different regions in Brazil. A total of 162 eyes were obtained from eye
banks in Manaus (n = 60), Sao Paulo (n = 60), Chapeco (n = 26), and Joinville (n
= 16). The retinas were macroscopically analyzed and collected for DNA
extraction. Real-time PCR (qPCR) was performed using the T. gondii B1 marker. By
qPCR, a higher frequency of T. gondii DNA in the retinas from the eye bank of
Joinville (25%) was found when compared to Manaus (5%). The retinas from Sao
Paulo and Chapeco were qPCR negative. Clinical examination determined the retina
lesions to be compatible with toxoplasmosis in the following frequencies:
Joinville (62.5%), Manaus (10%), Sao Paulo (6.7%), and Chapeco (15.4%).
PMID- 28508166
TI - Toxoplasma gondii and schizophrenia: a review of published RCTs.
AB - Over the last 60 years, accumulating evidence has suggested that acute, chronic,
and maternal Toxoplasma gondii infections predispose to schizophrenia. More
recent evidence suggests that chronically infected patients with schizophrenia
present with more severe disease. After acute infection, parasites form walled
cysts in the brain, leading to lifelong chronic infection and drug resistance to
commonly used antiparasitics. Chronic infection is the most studied and closely
linked with development and severity of schizophrenia. There are currently four
published randomized controlled trials evaluating antiparasitic drugs,
specifically azithromycin, trimethoprim, artemisinin, and artemether, in patients
with schizophrenia. No trials have demonstrated a change in psychopathology with
adjunctive treatment. Published trials have either selected drugs without
evidence against chronic infection or used them at doses too low to reduce brain
cyst burden. Furthermore, trials have failed to achieve sufficient power or
account for confounders such as previous antipsychotic treatment, sex, age, or
rhesus status on antiparasitic effect. There are currently no ongoing trials of
anti-Toxoplasma therapy in schizophrenia despite ample evidence to justify
further testing.
PMID- 28508167
TI - Lessons from a 15-year-old boy with advanced schistosomiasis japonica in China: a
case report.
AB - Schistosomiasis is a chronic, parasitic disease caused by flukes (trematodes) of
the genus Schistosoma, which presents the most important global burden of the 17
neglected tropical diseases listed by the World Health Organization. China has
made great achievements in schistosomiasis control, and now China is planning to
move forward, to eliminate schistosomiasis within 2020, but the fact cannot be
denied that the possibility of schistosome infection is still there in some
endemic due to its zoonotic nature as well as wide distribution of its
intermediate hosts (snails). Thus, how to interrupt the transmission in areas
with distribution of schistosomes and intermediate snails becomes a very serious
challenge that China is facing. In this paper, it is reported an advanced
schistosomiasis japonica case of a 15-year-old boy which is extremely rare in the
current schistosomiasis control in China. Thus, it is supposed to strengthen
health education of school children and to train professional physicians of local
hospitals.
PMID- 28508169
TI - Variation in the relationship between birth weight and subsequent obesity by
household income.
AB - There is evidence to suggest that high birth weight increases subsequent BMI.
However, little attention has been paid to variations in this impact between
population groups. This study investigates the relationship between high birth
weight and subsequent obesity, and whether or not this relationship varies by
household income. Data was taken from fourteen rounds of the Health Survey for
England (between 2000-2014; N = 31,043) for children aged 2-16. We regressed
obesity in childhood against birth weight, accounting for interactions between
birth weight and household income, using sibling-fixed effects models. High birth
weight was associated with increased risk of subsequent obesity. This association
was significantly more pronounced in children from low-income families, compared
with children from high-income families. A 1 kg increase in birth weight
increased the probability of obesity by 7% in the lowest income tertile and 4% in
the highest income tertile. This suggests that early socioeconomic deprivation
compound the effect of high birth weight on obesity.
PMID- 28508168
TI - Distinct Histone Modifications Modulate DEFB1 Expression in Human Vaginal
Keratinocytes in Response to Lactobacillus spp.
AB - Vaginal commensal lactobacilli are considered to contribute significantly to the
control of vaginal microbiota by competing with other microflora for adherence to
the vaginal epithelium and by producing antimicrobial compounds. However, the
molecular mechanisms of symbiotic prokaryotic-eukaryotic communication in the
vaginal ecosystem remain poorly understood. Here, we showed that both DNA
methylation and histone modifications were associated with expression of the
DEFB1 gene, which encodes the antimicrobial peptide human beta-defensin-1, in
vaginal keratinocyte VK2/E6E7 cells. We investigated whether exposure to
Lactobacillus gasseri and Lactobacillus reuteri would trigger the epigenetic
modulation of DEFB1 expression in VK2/E6E7 cells in a bacterial species-dependent
manner. While enhanced expression of DEFB1 was observed when VK2/E6E7 cells were
exposed to L. gasseri, treatment with L. reuteri resulted in reduced DEFB1
expression. Moreover, L. gasseri stimulated the recruitment of active histone
marks and, in contrast, L. reuteri led to the decrease of active histone marks at
the DEFB1 promoter. It was remarkable that distinct histone modifications within
the same promoter region of DEFB1 were mediated by L. gasseri and L. reuteri.
Therefore, our study suggested that one of the underlying mechanisms of DEFB1
expression in the vaginal ecosystem might be associated with the epigenetic
crosstalk between individual Lactobacillus spp. and vaginal keratinocytes.
PMID- 28508170
TI - Viral Vector-Based Evaluation of Regulatory Regions in the Neuron-Specific
Enolase (NSE) Promoter in Mouse Cerebellum In Vivo.
AB - We investigated the neuron-specific enolase (NSE) promoter in terms of its
promoter strength and neuronal specificity in the cerebellum in vivo. The 1.8 kb
rat NSE promoter was divided into three regions, A (0.8 kb), B (0.7 kb), and C
(0.3 kb), starting from the 5' side. Then, we made various deletion constructs
and assessed them by virally expressing GFP under the control of one of the
deleted promoters. Removing region A reduced GFP expression to ~6% of that of the
original 1.8 kb promoter. Further deletion of region B (presence of region C
alone) did not influence the promoter strength, but removing region B from the
original 1.8 kb promoter reduced the GFP expression to ~6% of the original level,
similar to the level observed after deletion of region A. Immunohistochemistry
showed robust GFP expression in Purkinje cells and modest expression in
interneurons by the original promoter. Removing region A and/or region B
abolished the GFP expression in Purkinje cells in most cerebellar lobules, with
the expression in interneurons almost unchanged. These results suggest that
region C, which is a proximal 0.3 kb sequence, contains cis-acting elements that
drive transcription predominantly in interneurons. The addition of either region
A or B onto region C does not alter the promoter properties; however, the
addition of both regions A and B to region C drastically enhanced the promoter
activity in Purkinje cells, suggesting the synergistic action of cis-acting
regulatory elements in regions A and B for strong activation in Purkinje cells.
PMID- 28508171
TI - Over-expression of tobacco UBC1 encoding a ubiquitin-conjugating enzyme increases
cadmium tolerance by activating the 20S/26S proteasome and by decreasing Cd
accumulation and oxidative stress in tobacco (Nicotiana tabacum).
AB - Ubiquitin (Ub)-conjugating enzyme (UBC, E2) receives Ub from Ub-activating enzyme
(E1) and transfers it to target proteins, thereby playing a key role in Ub/26S
proteasome-dependent proteolysis. UBC has been reported to be involved in
tolerating abiotic stress in plants, including drought, salt, osmotic and water
stresses. To isolate the genes involved in Cd tolerance, we transformed WT (wild
type) yeast Y800 with a tobacco cDNA expression library and isolated a tobacco
cDNA, NtUBC1 (Ub-conjugating enzyme), that enhances cadmium tolerance. When
NtUBC1 was over-expressed in tobacco, cadmium tolerance was enhanced, but the Cd
level was decreased. Interestingly, 20S proteasome activity was increased and
ubiquitinated protein levels were diminished in response to cadmium in NtUBC1
tobacco. By contrast, proteasome activity was decreased and ubiquitinated protein
levels were slightly enhanced by Cd treatment in control tobacco, which is
sensitive to Cd. Moreover, the oxidative stress level was induced to a lesser
extent by Cd in NtUBC1 tobacco compared with control plants, which is ascribed to
the higher activity of antioxidant enzymes in NtUBC1 tobacco. In addition, NtUBC1
tobacco displayed a reduced accumulation of Cd compared with the control, likely
due to the higher expression of CAX3 (Ca2+/H+ exchanger) and the lower expression
of IRT1 (iron-responsive transporter 1) and HMA-A and -B (heavy metal ATPase). In
contrast, atubc1 and atubc1atubc2 Arabidopsis exhibited lower Cd tolerance and
proteasome activity than WT. In conclusion, NtUBC1 expression promotes cadmium
tolerance likely by removing cadmium-damaged proteins via Ub/26S proteasome
dependent proteolysis or the Ub-independent 20S proteasome and by diminishing
oxidative stress through the activation of antioxidant enzymes and decreasing Cd
accumulation due to higher CAX3 and lower IRT1 and HMA-A/B expression in response
to 50 uM Cd challenge for 3 weeks.
PMID- 28508172
TI - Targeting Enolase in Reducing Secondary Damage in Acute Spinal Cord Injury in
Rats.
AB - Spinal cord injury (SCI) is a complex debilitating condition leading to permanent
life-long neurological deficits. The complexity of SCI suggests that a concerted
multi-targeted therapeutic approach is warranted to optimally improve function.
Damage to spinal cord is complicated by an increased detrimental response from
secondary injury factors mediated by activated glial cells and infiltrating
macrophages. While elevation of enolase especially neuron specific enolase (NSE)
in glial and neuronal cells is believed to trigger inflammatory cascades in acute
SCI, alteration of NSE and its subsequent effects in acute SCI remains unknown.
This study measured NSE expression levels and key inflammatory mediators after
acute SCI and investigated the role of ENOblock, a novel small molecule inhibitor
of enolase, in a male Sprague-Dawley (SD) rat SCI model. Serum NSE levels as well
as cytokines/chemokines and metabolic factors were evaluated in injured animals
following treatment with vehicle alone or ENOblock using Discovery assay. Spinal
cord samples were also analyzed for NSE and MMPs 2 and 9 as well as glial markers
by Western blotting. The results indicated a significant decrease in serum
inflammatory cytokines/chemokines and NSE, alterations of metabolic factors and
expression of MMPs in spinal cord tissues after treatment with ENOblock (100
ug/kg, twice). These results support the hypothesis that activation of glial
cells and inflammation status can be modulated by regulation of NSE expression
and activity. Analysis of SCI tissue samples by immunohistochemistry confirmed
that ENOblock decreased gliosis which may have occurred through reduction of
elevated NSE in rats. Overall, elevation of NSE is deleterious as it promotes
extracellular degradation and production of inflammatory cytokines/chemokines and
metabolic factors which activates glia and damages neurons. Thus, reduction of
NSE by ENOblock may have potential therapeutic implications in acute SCI.
PMID- 28508173
TI - Neuroprotective Effects of Lycium barbarum Polysaccharide on Focal Cerebral
Ischemic Injury in Mice.
AB - Increasing evidence demonstrates inflammation contributes to neuronal death
following cerebral ischemia. Lycium barbarum polysaccharide (LBP) has been
reported to prevent scopolamine-induced cognitive and memory deficits. We
recently indicated that LBP exerts neuroprotective effect against focal cerebral
ischemic injury in mice via attenuating the mitochondrial apoptosis pathway. The
aim of this study was to investigate the neuroprotective effects of LBP against
the behavioral dysfunction induced by focal cerebral ischemia injury in mice.
Following 7 successive days of pretreatment with LBP (10, 20 and 40 mg/kg) and
nimodipine (4 mg/kg) by intragastric gavage, mice were subjected to middle
cerebral artery occlusion (MCAO). Following reperfusion, cerebral blood flows,
the total power of the spontaneous EEG, and morphological changes were estimated.
Learning and memory ability, and motor coordination were determined by Morris
water maze task, rotarod and grip test. Western blot analysis, Real-Time
fluorogenic PCR assays, and immunofluorescence staining were used to examine the
expression of proinflammatory mediators and activation of microglia. The present
study showed that LBP pretreatment significantly enhanced regional cortical blood
flow and the total power of the spontaneous EEG, improved memory and motor
coordination impairments, and inhibited over-activation of microglia and
astrocytes after MCAO. Further study demonstrated LBP suppressed MCAO-induced
activations of P65 NF-kappaB and P38 MAPK, and prevented up-regulations of
proinflammatory mediators in hippocampus. Our data suggest that LBP can exert
functional recovery of memory and motor coordination deficits and neuroprotective
effect against cerebral ischemic injury in mice.
PMID- 28508175
TI - Comparison of R-CVP with R-CHOP for very elderly patients aged 80 or over with
diffuse large B cell lymphoma.
PMID- 28508174
TI - Preclinical Comparison of Mechanistically Different Antiseizure, Antinociceptive,
and/or Antidepressant Drugs in a Battery of Rodent Models of Nociceptive and
Neuropathic Pain.
AB - The series of experiments herein evaluated prototype drugs representing different
mechanisms of antiseizure, antinociceptive or antidepressant action in a battery
of preclinical pain models in adult male CF#1 mice (formalin, writhing, and tail
flick) and Sprague Dawley rats partial sciatic nerve ligation (PSNL). In the
formalin assay, phenytoin (PHT, 6 mg/kg), sodium valproate (VPA, 300 mg/kg),
amitriptyline (AMI, 7.5 and 15 mg/kg), gabapentin (GBP, 30 and 70 mg/kg),
tiagabine (TGB, 5 and 15 mg/kg), and acetominophen (APAP, 250 and 500 mg/kg)
reduced both phases of the formalin response to <= 25% of vehicle-treated mice.
In the acetic acid induced writhing assay, VPA (300 mg/kg), ethosuximide (ETX,
300 mg/kg), morphine (MOR, 5 & 10 mg/kg), GBP (10, 30, and 60 mg/kg), TGB (15
mg/kg), levetiracetam (LEV, 300 mg/kg), felbamate (FBM, 80 mg/kg) and APAP (250
mg/kg) reduced writhing to <= 25% of vehicle-treated mice. In the tail flick
test, MOR (1.25-5 mg/kg), AMI (15 mg/kg) and TGB (5 mg/kg) demonstrated
significant antinociceptive effects. Finally, carbamazepine (CBZ, 20 and 50
mg/kg), VPA, MOR (2 and 4 mg/kg), AMI (12 mg/kg), TPM (100 mg/kg), lamotrigine
(LTG, 40 mg/kg), GBP (60 mg/kg), TGB (15 mg/kg), FBM (35 mg/kg), and APAP (250
mg/kg) were effective in the PSNL model. Thus, TGB was the only prototype
compound with significant analgesic effects in each of the four models, while
AMI, GBP, APAP, and MOR each improved three of the four pain phenotypes. This
study highlights the importance evaluating novel targets in a variety of pain
phenotypes.
PMID- 28508176
TI - The prognostic role of CD68 and FoxP3 expression in patients with primary central
nervous system lymphoma.
AB - The prognostic role of CD68 and FoxP3 in primary central nervous system lymphoma
(PCNSL) has not been evaluated. Thus, we examined the prognostic significance of
CD68 and FoxP3 expression in tumor samples of 76 newly diagnosed immunocompetent
PCNSL patients. All patients were treated initially with high-dose methotrexate
(HD-MTX)-based chemotherapy, and 16 (21.1%) patients received upfront autologous
stem cell transplantation (ASCT) consolidation. High expression of CD68 (>55
cells/high-power field) or FoxP3 (>15 cells/high-power field) was observed in 10
patients, respectively. High CD68 expression was associated with inferior overall
survival (OS) and progression-free survival (PFS) in multivariate analysis (P =
0.023 and P = 0.021, respectively). In addition, we performed subgroup analysis
based on upfront ASCT. High CD68 expression was also associated with inferior OS
and PFS in multivariate analysis (P = 0.013 and P < 0.001, respectively) among
patients who did not receive upfront ASCT (n = 60), but not in patients who
received upfront ASCT. The expression of FoxP3 was not significantly associated
with survival. Therefore, we identified a prognostic significance of high CD68
expression in PCNSL, which suggests a need for further clinical trials and
biological studies on the role of PCNSL tumor microenvironment.
PMID- 28508177
TI - Standing Postural Control in Individuals with Autism Spectrum Disorder:
Systematic Review and Meta-analysis.
AB - Impairments in postural control affect the development of motor and social skills
in individuals with autism spectrum disorder (ASD). This review compared the
effect of different sensory conditions on static standing postural control
between ASD and neurotypical individuals. Results from 19 studies indicated a
large difference in postural control between groups across all sensory
conditions. This review revealed sensorimotor and multiple sensory processing
deficits in ASD. The tendency for individuals with ASD to be more susceptible to
postural instability with use of visual information compared with somatosensory
information suggests perinatal alterations in sensory development. There is
further scope for studies on the use of sensory information and postural control
to provide additional evidence about sensorimotor processing in ASD.
PMID- 28508178
TI - Survey about the use of clarithromycin in an ENT outpatient department of a
tertiary hospital.
AB - We undertook this survey about the use of clarithromycin in the Ear, Nose, and
Throat (ENT) Outpatient Department of Fudan University Hospital to understand its
utilization patterns and rational use. A survey of prescriptions given to
outpatients was carried out, and detailed information of the patients, including
age, sex, diagnosis, combined medication, and other information, was recorded in
Excel spreadsheets. The rationale for each prescription was evaluated
retrospectively. Based on our analysis, 82.5% of the clarithromycin prescriptions
were for the treatment of rhinosinusitis. It was found that the parameters for
the diagnosis of this condition were surprisingly broad and should have been more
specific. In addition, the clarithromycin dosage regimen varied in clinical
practice. For chronic rhinosinusitis, the duration of treatment was between 8 and
16 days, which was not sufficient. Moreover, clarithromycin was prescribed along
with considerable numbers of pharmacotherapeutic anti-allergic drugs. Our survey
indicated that improvements in the quality of clarithromycin prescriptions in
otolaryngology outpatients should be made. Furthermore, the importance of medical
education to patients should be emphasized. In addition, the interaction between
clarithromycin and other anti-allergic drugs requires further investigation.
PMID- 28508179
TI - Sternocleidomastoid flap augmentation of the pharyngeal closure after total
laryngectomy.
AB - The objective of the study was to evaluate the effect of sternocleidomastoid
(SCM) flap augmentation of the pharyngeal closure after total laryngectomy on the
incidence of pharyngocutaneous fistula (PCF). Thirty patients with T4a laryngeal
carcinoma and none of them receiving primary radiotherapy previously were divided
into two equal groups. Group A patients had SCM flap augmentation of the
pharyngeal closure after total laryngectomy. Group B patients had the standard
pharyngeal closure without augmentation. Both groups were followed up for 30 days
postoperatively for the development of PCF. The use of the SCM added about extra
15 min to the surgical procedure in all patients (p < 0.001). The shape of the
suture line of the neopharynx was horizontal in 14 patients (7 in each group)
while it was T-shaped in the remaining 16 (8 in each group). Neck dissection was
done in all patients except only two patients who previously had the neck
dissection done in combination with partial laryngectomy. Three patients in each
group developed PCF either early (10 days or less postoperatively) or late (more
than 10 days but less than 30 days postoperatively). There was no statistically
significant difference in the length of hospital stay between the two groups. The
use of SCM flap did not reduce the incidence of PCF after total laryngectomy.
PMID- 28508180
TI - A study evaluating the effects of throat packs during nasal surgery: a randomised
controlled trial.
AB - The aims of this study were to identify differences in post-operative nausea and
vomiting (PONV) and throat pain between throat packed and non-packed patient
groups in nasal surgery. This was a prospective, double blind, randomised
controlled trial. A water-soaked throat pack gauze was inserted in the mouth to
occlude the oropharynx was used in the throat pack group. The second group
received no throat pack. A validated PONV questionnaire was completed 6 h post
operatively. Visual analogue scores (VAS) for throat pain were completed in
recovery, 2, and 6 h post-operatively. 80 patients were enrolled (40 into each
group based on power calculation). With regard to the primary outcome measure,
mean PONV score for the throat pack group was 2.75 [median 0, standard deviation
(SD 10.86)] and the mean PONV score for the non-packed group was 0.36 (median 0,
SD 1.39). The difference in PONV was not statistically significant [P value
0.375, 95% confidence interval (CI) -1.19 to 3.32]. With regard to throat pain
VAS scores (our secondary outcome measure), in recovery, the mean throat pain VAS
score for the throat packed group was 2.5 (median 1, SD 2.8) and the mean throat
pain VAS score for the non-throat packed group was 1.3 (median 0, SD 2.5).
Statistical analysis showed a significant difference between the two groups with
the throat pack group experiencing more throat pain in recovery (P value 0.018
(95% CI 1.13-2.52). At 2 and 6 h post-operatively, the mean throat pain VAS
scores for the throat packed group were 2.1 and 2.3, respectively, and the mean
throat pain VAS score for the non-throat packed group was 2.3 and 1.4,
respectively. Statistical analysis showed non-significant difference between the
two groups at 2 and 6 h post-operatively. The use of throat packs in nasal
surgery does not confer PONV reduction benefit. The use of throat pack, however,
is associated with a small but statistically significant more throat pain in the
initial recovery period from nasal operations.
PMID- 28508181
TI - How we do it: the intra-operative identification of a pharyngocele.
AB - A pharyngocele is an uncommon condition, where pharyngeal mucosa herniates
through the thyrohyoid membrane. It can be difficult to locate when the patient
is at rest. To locate the pharyngocele intra-operatively, a bag valve mask was
used to inflate the herniated mucosa. We describe a cost-effective and simple way
to locate the pharyngocele intra-operatively.
PMID- 28508182
TI - New antimicrobial flavonoids and chalcone from Colutea armata.
AB - Colucins A (1) and B (2), new flavonoids and colucone (3), the new chalcone
derivative, have been isolated from the CHCl3-soluble fraction of the whole plant
of Colutea armata along with luteolin (4), luteolin 7-O-beta-D-glucoside (5),
isoliquiritigenin (6), trans-caffeic acid (7) and stigmasterol (8) reported for
the first time from this species. Their structures were elucidated by
spectroscopic techniques including MS and 2D-NMR spectroscopy. Compounds 1 and 2
showed significant antimicrobial activity against two Gram positive and three
Gram negative bacterial strains while 3 was moderately active.
PMID- 28508183
TI - Compositional design and Taguchi optimization of hardness properties in silicone
based ocular lenses.
AB - A multi-component acrylate-based copolymer system especially designed for
application as ocular lenses is developed through free-radical, bulk
polymerization of a system containing hydroxyethyl methacrylate, methyl
methacrylate, triethylene glycol dimethacrylate, dimethyl itaconate, 3
(trimethoxysilyl) propylmethacrylate, Polyhedraloligomeric silsesquioxane
acrylate (POSS-acrylate) and AIBN as an initiator. The progress of the reaction
was monitored by Fourier transform infrared spectroscopy (FTIR). The effect of
increasing concentration of the components on the hardness of the synthesized
lenses was measured by Shore Durometer before and after immersion in PBS
solutions. Extraction test method was performed to analyze the biocompatibility
of the fabricated lenses. In this research the Taguchi method was employed to
achieve the optimal hardness property which plays a critical role in final
application of the lens materials. The Taguchi trial for ocular lens hardness was
configured in an L16 orthogonal array, by five control factors, each with four
level settings. The results showed that 3-(trimethoxysilyl) propyl methacrylate
decreases and 2-hydroxyethylmethacrylate increases, polyhedraloligomeric
silsesquioxane with a cage-like structure, methyl methacrylate and dimethyl
itaconate increase the hardness. Proliferation and growth of the cells showed
that there is no toxic substance extracted from the lenses which can interfere
with the cell growth.
PMID- 28508184
TI - Nationwide cross-sectional adherence to mammography screening guidelines:
national behavioral risk factor surveillance system survey results.
AB - PURPOSE: Varying recommendations about breast cancer screening have generated
much confusion about when and how often to undergo mammography screening, yet
there is limited population-based data about the extent to which patients adhere
to various mammographic screening guidelines in practice. Our purpose was to
evaluate population-based adherence to mammographic screening using criteria from
major guideline-producing organizations. METHODS: Women aged 40-74 in the 2014
Behavioral Risk Factor Surveillance System survey were included. Self-reported
mammographic screening within 1 or 2 years, according to major guideline
producing organizations (American Cancer Society [ACS], US Preventative Services
Task Force [USPSTF], American College of Radiology [ACR], American College of
Obstetricians and Gynecologists [ACOG]) was calculated with logistic regression,
adjusting for demographics and indices of access to health care. RESULTS: 159,123
women were included. By age category, cross-sectional adherence to USPSTF
guidelines ranged from 76 to 81%, ACS (55-81%) and ACR/ACOG (45-64%) with
increasing age being associated improved adherence. The highest proportions of
women undergoing mammographic screening were seen in women ages 65-69 (66% within
last year, 81% within last 2 years). Statistically significant predictors of
adherence to mammography screening included increased income category (OR 1.08,
1.07-1.09), higher education category (OR 1.13, 1.11-1.16), and increased access
to health care (OR 2.25, 1.94-2.60), adjusted for age categories. CONCLUSIONS:
Adherence to mammography screening was closest to USPSTF guidelines with 76-81%
cross-sectional adherence. Frequency of screening increases with age with highest
screening proportions in women ages 65-69 (66% within last year, 81% within last
2 years). For all screening guidelines, adherence to mammography screening
remains poor in women with limited access to health insurance with less than half
of women obtaining recommended screening.
PMID- 28508186
TI - Effects of Maternal Zinc Glycine on Mortality, Zinc Concentration, and
Antioxidant Status in a Developing Embryo and 1-Day-Old Chick.
AB - This study was conducted to investigate the effects of maternal zinc glycine (Zn
Gly) supplementation as an alternative for zinc sulfate (ZnSO4) on mortality,
zinc (Zn) concentration, and antioxidant status in a developing embryo and 1-day
old chick. Six hundred 39-week-old broiler breeders were randomly assigned to 6
treatments, each treatment including 5 replicates with 20 birds each. Six
treatments received a basal diet (control, 24 mg Zn/kg diet) or a basal diet
supplemented with ZnSO4 (80 mg Zn/kg) or Zn-Gly (20, 40, 60, or 80 mg Zn/kg),
respectively. The experiment lasted for 8 weeks after a 4-week pre-experiment
with a basal diet. At the last week, 100 eggs per replicate were randomly
collected for incubation. Compared with the control treatment, Zn supplementation
decreased (P < 0.05) embryo mortalities of the late stage and the whole period,
increased (P < 0.05) liver Zn concentration in the embryo of d9, d19, and 1-day
old chick, and improved (P < 0.05) antioxidant status in the embryo of d19 and 1
day-old chick. Compared with the ZnSO4 treatment, 80 mg Zn/kg Zn-Gly treatment
significantly decreased (P < 0.05) the late stage embryo mortality and increased
(P < 0.05) liver Zn concentration in the embryo of d9, d19, and 1-day-old chick.
The 80 mg Zn/kg Zn-Gly treatment significantly increased (P < 0.05) copper-zinc
superoxide dismutase activity in d19 embryo and 1-day-old chick, total superoxide
dismutase activity in 1-day-old chick, and copper-zinc superoxide dismutase
messenger RNA (mRNA) abundance of d9 embryo and 1-day-old chick than that in
ZnSO4 treatment. The liver metallothionein concentration of the developing embryo
and 1-day-old chick and its mRNA abundance of d19 embryo were also significantly
increased (P < 0.05) in the 80 mg Zn/kg Zn-Gly treatment in comparison with ZnSO4
treatment. In conclusion, maternal Zn supplementation decreased embryo
mortalities of the late stage and the whole period by increasing liver Zn
concentration and antioxidant status in d19 embryo and 1-day-old chick, and 80 mg
Zn/kg from Zn-Gly treatment was the optimum choice.
PMID- 28508187
TI - Associations Between Serum Zinc Levels and Mental Health: Findings from the 2010
Korean National Health and Nutrition Examination Survey.
AB - Mental health problems are a major public health issue worldwide, and zinc may be
associated with psychiatric symptoms, but such associations have not been
investigated extensively. This study was conducted to evaluate the relationship
between serum zinc levels and mental health problems in Korean adults. We used
data from the Korean National Health and Nutrition Examination Survey V-1, a
cross-sectional survey of Korean civilians. Data from 1748 subjects were
analyzed. Serum zinc levels did not differ significantly according to psychiatric
symptoms including sleep duration, stress, depressed mood, suicidal ideation, and
whether respondents sought psychiatric consultation. The frequencies and odds
ratios of psychiatric symptoms according to serum zinc tertiles were not
significantly associated after adjusting for age, smoking, alcohol consumption,
physical activity, body mass index, total body fat, and renal function and for
daily fat, carbohydrate, and protein intake. Serum zinc levels may not be
associated with psychiatric symptoms in Korean adults without psychiatric
disorders.
PMID- 28508185
TI - TITAN: phase III study of doxorubicin/cyclophosphamide followed by ixabepilone or
paclitaxel in early-stage triple-negative breast cancer.
AB - PURPOSE: Ixabepilone is a microtubule stabilizer with activity in taxane
refractory metastatic breast cancer and low susceptibility to taxane-resistance
mechanisms including multidrug-resistant phenotypes and high beta-III tubulin
expression. Since these resistance mechanisms are common in triple-negative
breast cancer (TNBC), ixabepilone may have particular advantages in this patient
population. This study evaluated the substitution of ixabepilone for paclitaxel
following doxorubicin/cyclophosphamide (AC) in the adjuvant treatment of early
stage TNBC. METHODS: Patients with operable TNBC were eligible following
definitive breast surgery. Patients were randomized (1:1) to receive four cycles
of AC followed by either four cycles (12 weeks) of ixabepilone or 12 weekly doses
of paclitaxel. RESULTS: 614 patients were randomized: 306 to AC/ixabepilone and
308 to AC/paclitaxel. At a median follow-up of 48 months, 59 patients had
relapsed (AC/ixabepilone, 29; AC/paclitaxel, 30). The median time from diagnosis
to relapse was 20.8 months. The 5-year disease-free survival (DFS) rates of the
two groups were similar [HR 0.92; ixabepilone 87.1% (95% CI 82.6-90.5) vs.
paclitaxel 84.7% (95% CI 79.7-88.6)]. The estimated 5-year overall survival (OS)
rates were also similar [HR 1.1; ixabepilone 89.7% (95% CI 85.5-92.7) vs.
paclitaxel 89.6% (95% CI 85.0-92.9)]. Peripheral neuropathy was the most common
grade 3/4 event. Dose reductions and treatment discontinuations occurred more
frequently during paclitaxel treatment. CONCLUSIONS: Treatment with
AC/ixabepilone provided similar DFS and OS in patients with operable TNBC when
compared to treatment with AC/paclitaxel. The two regimens had similar toxicity,
although treatment discontinuation, dose modifications, and overall peripheral
neuropathy were more frequent with AC/paclitaxel. TRIAL REGISTRATION: Clinical
Trials.gov Identifier, NCT00789581.
PMID- 28508188
TI - Trace Element Determination and Cardioprotection of Terminalia pallida Fruit
Ethanolic Extract in Isoproterenol Induced Myocardial Infarcted Rats by ICP-MS.
AB - The trace elements and minerals in Terminalia pallida fruit ethanolic extract
(TpFE) were determined by the instrument inductively coupled plasma-mass
spectrometry (ICP-MS), and the cardioprotection of TpFE against isoproterenol
(ISO)-administered rats was studied. Rats were pretreated with TpFE (100, 300,
and 500 mg/kg bw) for 30 days, with concurrent administration of ISO (85 mg/kg
bw) for two consecutive days. The levels of trace elements and minerals in TpFE
were below the permitted limits of World Health Organization standards. ISO
administration significantly increased the heart weight and cardiac marker
enzymes in serum, xanthine oxidase, sodium, and calcium in the heart, whereas
significantly decreased body weight, reduced glutathione, glutathione-S
transferase, superoxide dismutase, and potassium in the heart. Oral pretreatment
of TpFE significantly prevented the ISO-induced alterations. This is the first
report that revealed the determination of trace elements and mineral nutrients of
TpFE by ICP-MS which plays a principal role in the herbal drug discovery for the
treatment of cardiovascular diseases.
PMID- 28508189
TI - The Contribution of Superoxide Radical to Cadmium Toxicity in E. coli.
AB - Numerous reports suggest the involvement of oxidative stress in cadmium toxicity,
but the nature of the reactive species and the mechanism of Cd-induced oxidative
damage are not clear. In this study, E. coli mutants were used to investigate
mechanisms of Cd toxicity. Effects of Cd on metabolic activity, production of
superoxide radical by the respiratory chain, and induction of enzymes controlled
by the soxRS regulon were investigated. In E. coli, the soxRS regulon controls
defense against O2.-and univalent oxidants. Suppression of metabolic activity,
inability of E. coli to adapt to new environment, and slow cell division were
among the manifestations of Cd toxicity. Cd increased production of O2.- by the
electron transport chain and prevented the induction of soxRS-controlled
protective enzymes, even when the regulon was induced by the redox-cycling agent,
paraquat. The effect was not limited to soxRS-dependent proteins and can be
attributed to previously reported suppression of protein synthesis by Cd.
Increased production of superoxide, combined with inability to express protective
enzymes and to replace damaged proteins by de novo protein synthesis, seems to be
the main reason for growth stasis and cell death in Cd poisoning.
PMID- 28508190
TI - Assessment of the Zinc and Copper Status in Alpaca.
AB - This study was performed with the aim of investigating the concentration of zinc
and copper in the blood of healthy alpacas (Vicugna pacos) kept in central Europe
and to compare the concentration of Zn and Cu in plasma and in whole blood. A
further objective was to evaluate blood Zn and Cu in relation to different
micromineral supplementation, age and sex groups of alpacas. A total of 299
alpacas (224 adults and 75 crias) from 18 farms were included in this study. The
concentrations of copper and zinc in plasma/whole blood were measured by flame
atomic absorption spectrometry. The results of this study show high individual
variability in plasma Zn (median 3.54, range 1.56-8.01 MUmol/l), whole blood Zn
(median 10.01, range 6.23-75.0 MUmol/l), plasma Cu (median 7.53, range 2.93-16.41
MUmol/l) and whole blood Cu (median 6.33, range 3.02-13.95 MUmol/l). Plasma Zn
was not significantly influenced by sex, age or feeding group. Whole blood Zn was
only significantly higher in females than in males. The intake of Zn in all
groups was equal to or higher than the nutritional recommendation. During
excessive supplementation, Zn absorption decreased and thus blood Zn did not
reflect the higher intake. Only a weak correlation was found (Spearman
correlation coefficient r = 0.384; p > 0.01; n = 204) between plasma and whole
blood Zn concentrations. Plasma copper concentration was significantly influenced
by age, sex and feeding; whole blood Cu by age and feeding. However, neither
plasma Cu nor whole blood Cu reflected the intake of the element. We found a
close correlation between plasma and blood copper concentrations (Spearman
correlation coefficient r = 0.9043; p <= 0.01; n = 99). According to our results,
copper in plasma or blood is not a good indicator of copper intake.
PMID- 28508191
TI - Investigations of severity level measurements for diabetic macular oedema using
machine learning algorithms.
AB - BACKGROUND: The macula is an important part of the human visual system and is
responsible for clear and colour vision. Macular oedema happens when fluid and
protein deposit on or below the macula of the eye and cause the macula to thicken
and swell. Normally, it occurs due to diabetes called diabetic macular oedema.
Diabetic macular oedema (DME) is one of the main causes of visual impairment in
patients. AIM: The aims of the present study are to detect and localize
abnormalities in blood vessels with respect to macula in order to prevent vision
loss for the diabetic patients. METHODS: In this work, a novel fully computerized
algorithm is used for the recognition of various diseases in macula using both
fundus images and optical coherence tomography (OCT) images. Abnormal blood
vessels are segmented using thresholding algorithm. The classification is
performed by three different classifiers, namely, the support vector machine
(SVM), cascade neural network (CNN) and partial least square (PLS) classifiers,
which are employed to identify whether the image is normal or abnormal.
CONCLUSION: The results of all of the classifiers are compared based on their
accuracy. The classifier accuracies of the SVM, cascade neural network and
partial least square are 98.33, 97.16 and 94.34%, respectively. While analysing
DME using both images, OCT produced efficient output than fundus images.
Information about the severity of the disease and the localization of the
pathologies is very useful to the ophthalmologist for diagnosing disease and
choosing the proper treatment for a patient to prevent vision loss.
PMID- 28508192
TI - Ultrasound-guided fine needle aspiration versus core needle biopsy: comparison of
post-biopsy hematoma rates and risk factors.
AB - PURPOSE: To compare post-biopsy hematoma rates between ultrasound guided-fine
needle aspiration and ultrasound guided-core needle biopsy, and to investigate
risk factors for post-biopsy hematoma. METHODS: A total of 5304 thyroid nodules
which underwent ultrasound guided biopsy were included in this retrospective
study. We compared clinical and US features between patients with and without
post-biopsy hematoma. Associations between these features and post-biopsy
hematoma were analyzed. RESULTS: Post-biopsy hematoma rate was 0.8% (43/5121) for
ultrasound guided-fine needle aspiration and 4.9% (9/183) for ultrasound guided
core needle biopsy (P < 0.001). For ultrasound guided-fine needle aspiration,
gender, age, size, presence of vascularity, and suspicious US features were not
associated with post-biopsy hematoma according to experience level. Post-biopsy
hematoma occurred significantly more with ultrasound guided-core needle biopsy
(9/179, 5.0%) than with ultrasound guided-fine needle aspiration (9/1138, 0.8%)
(P < 0.001) in experienced performers and ultrasound guided-core needle biopsy
was the only significant risk factor for post-biopsy hematoma (adjusted Odds
Ratio, 6.458, P < 0.001). CONCLUSION: Post-biopsy hematoma occurred significantly
more in ultrasound guided-core needle biopsy than in ultrasound guided-fine
needle aspiration and ultrasound guided-core needle biopsy was the only
independent factor of post-biopsy hematoma in thyroid nodules.
PMID- 28508193
TI - Neutrophil depletion improves diet-induced non-alcoholic fatty liver disease in
mice.
AB - PURPOSE: Non-alcoholic fatty liver disease is highly associated with morbidity
and mortality in population. Although studies have already demonstrated that the
immune response plays a pivotal role in the development of non-alcoholic fatty
liver disease, the comprehensive regulation is unclear. Therefore, present study
was carried out to investigate the non-alcoholic fatty liver disease development
under neutrophil depletion. METHODS: To achieve the aim of the study, C57BL/6 J
mice were fed with high fat diet for 6 weeks before treated with neutrophil
deplete antibody 1A8 or isotype control (200 MUg/ mouse every week) for another 4
weeks. RESULTS: Treated with 1A8 antibody, obese mice exhibited better whole body
metabolic parameters, including reduction of body weight gain and fasting blood
glucose levels. Neutrophil depletion also effectively reduced hepatic structural
disorders, dysfunction and lipid accumulation. Lipid beta-oxidative markers,
phosphorylated-AMP-activated protein kinase alpha and phosphorylated-acetyl-CoA
carboxylase levels were increased in 1A8 antibody-treated obese mouse group. The
mitochondrial number and function were also reversed after 1A8 antibody
treatment, including increased mitochondrial number, reduced lipid oxidative
damage and enhanced mitochondrial activity. Furthermore, the expression of
inflammatory cytokines, tumor necrosis factor-alpha, interleukin-6, and monocyte
chemoattractant protein-1 were obviously reduced after neutrophil depletion,
accompanied with decreased F4/80 mRNA level and macrophage percentage in liver.
The decreased NF-kappaB signaling activity was also involved in the beneficial
effect of neutrophil depletion. CONCLUSION: Taken together, neutrophil depletion
could attenuate metabolic syndromes and hepatic dysfunction.
PMID- 28508194
TI - Fatty liver as a risk factor for progression from metabolically healthy to
metabolically abnormal in non-overweight individuals.
AB - PURPOSE: Recent studies identified that metabolically abnormal non-obese
phenotype is a risk factor for cardiovascular diseases. However, little is known
about risk factor for progression from metabolically healthy non-overweight to
metabolically abnormal phenotype. We hypothesized that fatty liver had a clinical
impact on progression from metabolically healthy non-overweight to metabolically
abnormal phenotype. METHODS: In this retrospective cohort study, 14,093 Japanese
(7557 men and 6736 women), who received the health-checkup program from 2004 to
2012, were enrolled. Overweight and obesity were defined as body mass index 23.0
25.0 and >=25.0 kg/m2. Four metabolic factors (impaired fasting glucose,
hypertension, hypertriglyceridemia and low high density lipoprotein-cholesterol
concentration) were used for definition of metabolically healthy (less than two
factors) or metabolically abnormal (two or more). We divided the participants
into three groups: metabolically healthy non-overweight (9755 individuals,
men/women = 4290/5465), metabolically healthy overweight (2547 individuals,
1800/747) and metabolically healthy obesity (1791 individuals, 1267/524). Fatty
liver was diagnosed by ultrasonography. RESULTS: Over the median follow-up period
of 5.3 years, 873 metabolically healthy non-overweight, 512 metabolically healthy
overweight and 536 metabolically healthy obesity individuals progressed to
metabolically abnormal. The adjusted hazard risks of fatty liver on progression
were 1.49 (95% confidence interval 1.20-1.83, p = 0.005) in metabolically healthy
non-overweight, 1.37 (1.12-1.66, p = 0.002) in metabolically healthy overweight
and 1.38 (1.15-1.66, p < 0.001) in metabolically healthy obesity, after adjusting
for age, sex, alcohol, smoking, exercise, impaired fasting glucose, hypertension,
hypertriglyceridemia, low high density lipoprotein-cholesterol concentration, and
abdominal obesity. CONCLUSIONS: Fatty liver is an independent risk factor for
progression from metabolically healthy status to metabolically abnormal
phenotype, even in non-overweight individuals.
PMID- 28508196
TI - Genetic relationship and biological status of the industrially important yeast
Saccharomyces eubayanus Sampaio et al.
AB - The genomes of the recently discovered yeast Saccharomyces eubayanus and
traditional S. cerevisiae are known to be found in the yeast S. pastorianus (syn.
S. carlsbergensis), which are essential for brewing. The cryotolerant yeast S.
bayanus var. uvarum is of great importance for production of some wines. Based on
ascospore viability and meiotic recombination of the control parental markers in
hybrids, we have shown that there is no complete interspecies post-zygotic
isolation between the yeasts S. eubayanus, S. bayanus var. bayanus and S. bayanus
var. uvarum. The genetic data presented indicate that all of the three taxa
belong to the same species.
PMID- 28508195
TI - Serum p53 antibody as a potential tumor marker in extrahepatic
cholangiocarcinoma.
AB - PURPOSE: Only a few studies have evaluated the clinicopathological significance
of the p53 protein expression and s-p53-Abs level in patients with
cholangiocarcinoma. We therefore analyzed the clinicopathological and prognostic
significance of s-p53-Abs in patients with extrahepatic cholangiocarcinoma.
METHODS: We prospectively evaluated s-p53-Abs levels before and after surgery in
61 patients with extrahepatic cholangiocarcinoma to determine the relationship
between clinicopathological factors and the prognostic significance of s-p53-Abs.
RESULTS: Among a total of 61 primary extrahepatic cholangiocarcinoma cases, 23%
were positive for s-p53-Abs. Combination of s-p53-Abs with the conventional serum
markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9)
significantly increased the rate of positive extrahepatic cholangiocarcinoma
cases (57% for CEA and/or CA19-9 vs. 75% for CEA and/or CA19-9 and/or s-p53-Abs,
P = 0.035). There were no significant differences in clinicopathological factors
between the p53-seropositive and p53-seronegative patients. An
immunohistochemical analysis showed the presence of significant associations
between the intensity (P = 0.003) and extent (P = 0.001) of p53 immunoreactivity
and p53-seropositivitly. Although s-p53-Abs was not a significant prognostic
factor for the survival in either univariate or multivariate analyses, p53
immunoreactivity was independently associated with a poor survival. Among
patients positive for s-p53-Abs before surgery, the s-p53-Abs levels were reduced
after surgery in most. CONCLUSION: These findings suggested that s-p53-Abs might
be associated with p53 immunoreactivity. In addition, s-p53-Abs may be useful for
a diagnosis, but was not useful for predicting tumor recurrence or the survival.
This study was registered as UMIN000014530.
PMID- 28508197
TI - Antinociceptive effect of the agonist of 5-HT1A receptors buspirone in the model
of abdominal pain in dogs.
AB - We have demonstrated that activation of 5-HT1A receptors with buspirone promotes
visceral analgesia in awake dogs. The administration of 0.035 mg/kg (i.m.) of the
drug caused depression of viscero-motor (contraction of the abdominal muscles)
and pressor (increase in the heart rate) responses to noxious distension of the
large intestine. An increase in the dose to 0.07 and 0.14 mg/kg did not enhance
the antinociceptive effect of buspirone but triggered basal tachycardia. The
obtained results provide evidence of the inhibitory role of 5-HT1A receptors in
modulating visceral pain sensitivity and the possibility of an exciting effect of
their activation on the cardiovascular system.
PMID- 28508198
TI - Role of the low-selective organic anion transport in regulation of osmotic
balance of renal collecting duct principal cells under hypo-osmotic conditions.
AB - In the course of adaptation of the rat kidney collecting duct cells to hypo
osmotic medium, the organic anion transporter inhibitor probenecid reduced
significantly the regulatory cell volume decrease in response to a hypotonic
shock. Both probenecid and hypotonic shock delayed significantly the entry into a
cell of the fluorescent dye calcein, which exists as anion at neutral pH. Thus,
the organic osmolyte transport plays an important role in the regulatory decrease
of the principal cell volume under the hypo-osmotic conditions.
PMID- 28508199
TI - Selective specificity of calcium-binding proteins calbindin and calretinin
expression in the magnocellular neurosecretory hypothalamic nuclei of tortoises
and turtles.
AB - We have studied the distribution of calcium-binding proteins in the magnocellular
neurosecretory nuclei of nonapeptidergic neurosecretory nuclei of the preoptic
hypothalamic complex in a tortoise (Testudo horsfieldi) and a pond turtle (Emys
orbicularis) using immunohistochemistry. We have found that different types of
cells in the paraventricular and supraoptic nuclei predominantly express
calbindin and, to a lesser extent, calretinin, but not parvalbumin. The selective
calbindin/calretinin control of the neurohormone secretion in these hypothalamic
nuclei is an evolutionary conservative feature typical of reptiles and mammals.
PMID- 28508200
TI - Individual variability of human olfactory sensitivity to volatile steroids:
Environmental and genetic factors.
AB - The sensitivity to androstenone and possible factors, determining the sensitivity
were investigated for the large sample of inhabitants of central Russia (n =
860). Specific anosmia was detected in 48.8% of subjects. Women were more
sensitive to androstenone than men. The proportion of men, but not women
perceiving the smell of androstenone as a strong one in the concentration used
decreased with age. Smoking, blood group, or ethnicity had no significant effect
on the expression of specific anosmia and the perception of androstenone odor
intensity.
PMID- 28508201
TI - Heterochronies in the cranial development of Asian tree frogs (Amphibia: Anura:
Rhacophoridae) with different life histories.
AB - The development of bony skull was studied in four species of Asian tree frogs
(Rhacophoridae) with different life histories: biphasic development with free
larval stage and direct development. In biphasic rhacophorids the sequence of the
appearance of cranial bones generally followed the generalized pattern of
craniogenesis, which was described for most studied anurans. In contrast, direct
developing species displayed some heterochronies in the formation of skull bones,
namely, the accelerated formation of the anlagen of jaw and suspensorium bones.
The obtained results support that the embryonization in amphibians is regularly
accompanied by a heterochronic repatterning of craniogenesis, rather similar in
different phyletic groups.
PMID- 28508202
TI - Ozone concentration in the ground atmosphere and morbidity during extreme heat in
the summer of 2010.
AB - Dependence of the population morbidity on the ground-level ozone concentration in
the summer of 2010 was studied in a city with low urbanization (Vyatskie Polyany,
Kirov oblast) and in Moscow. At a high air temperature and low ozone
concentration, the population morbidity was not associated with these parameters
in Vyatskie Polyany. When the average daily ground-level ozone concentration
exceeded 60 MUg/m3 for 13 successive days, the correlation coefficient between
ozone concentration and the number of ambulance calls was statistically
significant, r = 0.62. Heavy smoke from forest fires reduced ozone concentration,
and the number of emergency calls did not increase. In Moscow, the incidence of
respiratory diseases and population mortality were growing up at high ozone
concentrations.
PMID- 28508203
TI - Plasma corticosterone concentrations in European robins during spring and autumn
migration.
AB - To estimate differences in hormonal mechanisms of regulation of spring and autumn
migration in European robins Erithacus rubecula, the plasma corticosterone (CORT)
concentrations were compared in birds caught during both migratory seasons. A
total of 414 blood samples were analyzed. It was found that the baseline and
stress-induced CORT concentrations in free-living robins during spring migration
were practically twice as high as during autumn passage. Our results demonstrate
that autumn and spring migrations are independent stages of the avian annual
cycle. Probably, the increase in the CORT concentrations in spring can be
considered to be physiological preparation for the breeding season.
PMID- 28508204
TI - Rearing by foster Wistar mother with high level of maternal care counteracts the
development of genetic absence epilepsy and comorbid depression in WAG/Rij rats.
AB - It has been shown for the first time that rearing by a foster Wistar mother with
high level of maternal care (MC) counteracts the expression of genetic absence
epilepsy (AE) and comorbid depression - reduces the number, duration and index of
spike-wave discharges (SWDs) and immobility time in the forced swimming test, as
well as exerts substantial effects on morphology and time-frequency dynamics of
SWDs in WAG/Rij rats. It is supposed that increases in MC early in development
might be used to counteract epileptogenesis and comorbid depression in people
genetically predisposed to AE.
PMID- 28508205
TI - The first case of morphological differentiation of Altai Osman Oreoleuciscus
potanini (Cyprinidae, Actinopterigii) in a river.
AB - The variability of osteological characters has been investigated in cyprinid fish
of the genus Oreoleuciscus (Potanin Altai osman) from the river Zavkhan; this
fish species is endemic for water bodies of Central Asia. Multivariate analysis
of 13 quantitative parameters of the size of the cerebral and visceral skull and
the pectoral girdle and the construction of ontogenetic channels allowed the
detection of morphologically distinct forms in the fluvial habitats. The result
obtained provides additional proof of the possibility of sympatric
diversification of fish in river ecosystems. One of the two fluvial forms
discovered has been shown to be identical (with regard to the osteological
characters) to a previously described herbivorous form of O. potanini from the
standing water bodies of the Great Lakes Hollow (Western Mongolia).
PMID- 28508206
TI - Rapid use of resources as a basis of the Heracleum sosnowskyi invasive syndrome.
AB - The functional properties of the invasive Heracleum sosnowskyi were compared with
those of the native Heracleum sibiricum. The leaf and root traits, as well as
those of a whole plant and of the mycorrhiza formation, were studied. H.
sosnowskyi can fulfill the high-productivity potential only under the optimum
availability of resources (especially water), while it is poorly adapted to
maintain a high physiological activity under the unfavorable soil conditions. An
important component of the H. sosnowskyi invasiveness is an ability to utilize
rapidly resources in both the above- and underground areas at the optimum
conditions.
PMID- 28508207
TI - New aspects of the Seam4D-dependent control of lymphocyte activation.
AB - Novel targets for action of the class IV semaphorin Seam4D have been identified
in the immune system. The low-affinity CD72 receptor for Seam4D was detected not
only on B lymphocytes, but also in a proportion of T cells, whereas the high
affinity semaphorin receptor, plexin B1, originally considered to belong to non
immune cells, proved to be in a great proportion of intact T and B cells. Seam4D
is constitutively expressed in B cells, which, along with T cells, can serve as a
source of both membrane and soluble semaphorin. The results obtained make
significant adjustments in understanding of Seam4D effects in lymphoid cells.
PMID- 28508208
TI - The meio- to macrozoobenthos ratio in a lake benthic community: Dynamic aspect.
AB - Multiyear data (2002-2015) on the biomasses of meio- and macrozoobenthic
communities have been studied at different depths of a small lake in northern
Karelia. A trend towards anti-phase changes in meio- and macrobenthic biomasses
was observed and, as a consequence, the ratio between these components varied
significantly in different years. Thus, inter-annual dynamics should be taken
into account in analysis of hydrobiological data.
PMID- 28508209
TI - Estimates of underwater and aerial visual acuity in the European beaver Castor
fiber L. based on morphological data.
AB - The eye optics and topographic distribution of ganglion cells were studied using
whole mount preparations from European beaver Castor fiber L. The beaver eye
optics provides emmetropia in air and hypermetropia in water. The optometrical
measurements predict retinal resolution of the beaver eye around 17' in air and
9' in water. In air, retinal resolution corresponds to the real visual acuity,
whereas in water, visual acuity is below the retinal resolution because of the
non-precise focusing.
PMID- 28508210
TI - Reverse Genetics for Mammalian Orthoreovirus.
AB - Reverse genetics allows introduction of specific alterations into a viral genome.
Studies performed with mutant viruses generated using reverse genetics approaches
have contributed immeasurably to our understanding of viral replication and
pathogenesis, and also have led to development of novel vaccines and virus-based
vectors. Here, we describe the reverse genetics system that allows for production
and recovery of mammalian orthoreovirus, a double-stranded (ds) RNA virus, from
plasmids that encode the viral genome.
PMID- 28508211
TI - Development and Characterization of an Infectious cDNA Clone of Equine Arteritis
Virus.
AB - Development and characterization of several infectious cDNA clones of equine
arteritis virus (EAV) have been described in the literature. Here we describe the
assembly of the full-length infectious cDNA clone of the virulent Bucyrus strain
(VBS; ATCC VR-796) of EAV in a plasmid vector. This system allows generation of
infectious in vitro-transcribed (IVT) RNA from the linearized plasmid that can be
transfected or electroporated into mammalian cells to produce infectious
recombinant progeny virus. This is an efficient reverse genetics system that
allows easy manipulation of EAV genomes to study molecular biology of the virus
and pathogenesis of equine viral arteritis.
PMID- 28508212
TI - Reverse Genetics for Porcine Reproductive and Respiratory Syndrome Virus.
AB - Porcine reproductive and respiratory syndrome (PRRS) is a reemerging swine
disease, and has become economically the most significant disease in pork
production worldwide. The causative agent is PRRS virus (PRRSV), which is a
member virus of the family Arteriviridae. The PRRSV genome is a single-stranded
positive-sense RNA and is infectious. Two strategies in the PRRSV reverse
genetics system have been employed for reconstitution of progeny virus: RNA
transfection and DNA transfection. The PRRSV reverse genetics has broadly been
used for studies including protein structure-function relationship, foreign gene
expression, vaccine development, virulence determinants, and viral pathogenesis.
Herein, we describe the modification of the pFL12 "RNA launch" reverse genetic
system to the CMV promoter-driven pXJ41-FL13 "DNA launch" system. The generation
of progeny PRRSV using pXJ41-FL13 is further elucidated.
PMID- 28508213
TI - Reverse Genetics of Zika Virus.
AB - We have established a reverse genetic system for Zika virus (ZIKV). Five shuttle
plasmids were constructed and assembled into the full-length cDNA clone of ZIKV
genome. To ensure the stability of the cDNA clone, we used a low copy vector
(pACYC177) and a set of unique restriction enzyme sites on the ZIKV genome to
assemble the full-length cDNA clone. A T7 promoter was engineered in front of the
viral 5' UTR for in vitro transcription. A hepatitis delta virus ribozyme (HDVr)
sequence was engineered following the viral 3' UTR for generation of the
authentic 3' end of the RNA transcript.
PMID- 28508214
TI - Efficient Reverse Genetic Systems for Rapid Genetic Manipulation of Emergent and
Preemergent Infectious Coronaviruses.
AB - Emergent and preemergent coronaviruses (CoVs) pose a global threat that requires
immediate intervention. Rapid intervention necessitates the capacity to generate,
grow, and genetically manipulate infectious CoVs in order to rapidly evaluate
pathogenic mechanisms, host and tissue permissibility, and candidate antiviral
therapeutic efficacy. CoVs encode the largest viral RNA genomes at about 28
32,000 nucleotides in length, and thereby complicate efficient engineering of the
genome. Deconstructing the genome into manageable fragments affords the
plasticity necessary to rapidly introduce targeted genetic changes in parallel
and assort mutated fragments while maximizing genome stability over time. In this
protocol we describe a well-developed reverse genetic platform strategy for CoVs
that is comprised of partitioning the viral genome into 5-7 independent DNA
fragments (depending on the CoV genome), each subcloned into a plasmid for
increased stability and ease of genetic manipulation and amplification.
Coronavirus genomes are conveniently partitioned by introducing type IIS or IIG
restriction enzyme recognition sites that confer directional cloning. Since each
restriction site leaves a unique overhang between adjoining fragments,
reconstruction of the full-length genome can be achieved through a standard DNA
ligation comprised of equal molar ratios of each fragment. Using this method,
recombinant CoVs can be rapidly generated and used to investigate host range,
gene function, pathogenesis, and candidate therapeutics for emerging and
preemergent CoVs both in vitro and in vivo.
PMID- 28508216
TI - Rescue of Sendai Virus from Cloned cDNA.
AB - Sendai virus (SeV) is a non-segment negative-sense RNA virus that naturally
infects and causes pneumonia in mice. As a prototypic member of the family
Paramyxoviridae, SeV has been characterized well, and these studies revealed
numerous traits of paramyxovirus biology. The reverse genetics system to rescue
SeV was first established in 1995. The virus was rescued from a cloned cDNA that
contains full genome sequence flanked by T7 promoter and hepatitis delta virus
ribozyme. To rescue SeV, it is necessary to infect cells with a recombinant
vaccinia virus vTF7.3 that expresses T7 RNA polymerase, and transfect with the
SeV full genome cDNAs together with supporting plasmids encoding NP, P, and L
genes under the T7 promoter. Synthesized viral RNA by T7 RNA polymerase will be
encapsidated with NP and associated with a polymerase complex composed of P and
L. The polymerase complex transcribes and replicates the genome, and produces
progeny virions. Rescued SeV needs to be plaque purified to exclude vTF7.3 from
viral stock. Reverse genetics system of SeV is relatively efficient compared to
other paramyxoviruses, but alternative approaches to rescue poorly growing mutant
viruses are also available.
PMID- 28508215
TI - Reverse Genetics System for the Avian Coronavirus Infectious Bronchitis Virus.
AB - We have developed a reverse genetics system for the avian coronavirus infectious
bronchitis virus (IBV) in which a full-length cDNA corresponding to the IBV
genome is inserted into the vaccinia virus genome under the control of a T7
promoter sequence. Vaccinia virus as a vector for the full-length IBV cDNA has
the advantage that modifications can be introduced into the IBV cDNA using
homologous recombination, a method frequently used to insert and delete sequences
from the vaccinia virus genome. Here, we describe the use of transient dominant
selection as a method for introducing modifications into the IBV cDNA that has
been successfully used for the substitution of specific nucleotides, deletion of
genomic regions, and exchange of complete genes. Infectious recombinant IBVs are
generated in situ following the transfection of vaccinia virus DNA, containing
the modified IBV cDNA, into cells infected with a recombinant fowlpox virus
expressing T7 DNA-dependant RNA polymerase.
PMID- 28508217
TI - BAC-Based Recovery of Recombinant Respiratory Syncytial Virus (RSV).
AB - Respiratory syncytial virus (RSV) is an enveloped, nonsegmented negative-strand
RNA virus, which causes lower respiratory tract infections and is a leading cause
of mortality in young infants. There is no available RSV vaccine and currently
administered prophylactic antibodies are limited to high-risk populations.
Current efforts to develop vaccines include development of live-attenuated RSV
candidates. We describe here methods for preparation and recovery of recombinant
RSV using an efficient bacterial artificial chromosome (BAC)-based system,
expansion and plaque purification of recovered virus, and generation of master
and working stocks.
PMID- 28508218
TI - Recovery of a Paramyxovirus, the Human Metapneumovirus, from Cloned cDNA.
AB - Human metapneumovirus (HMPV), a single-stranded negative-sense RNA virus
belonging to the family Paramyxoviridae, is associated with respiratory tract
illness, primarily in young children and persons with underlying disease. Based
on genetic and antigenic variation, HMPV strains are classified into two
serotypes, with isolates NL/1/00 and NL/1/99 as prototypes for serotypes A and B,
respectively. The development of plasmid-based reverse genetics systems for both
serotypes has resulted in developments of a wide range of vaccine candidates
against HMPV infection. The approach to virus rescue of HMPV is similar to that
used for other paramyxoviruses, starting with mini-replicon assays for
optimizations of the rescue protocols and subsequent replacement of the mini
genome with a plasmid expressing the cDNA of the full-length viral RNA genome.
Here, we provide detailed information on the reverse genetics systems for HMPV.
PMID- 28508219
TI - Reverse Genetics of Newcastle Disease Virus.
AB - Reverse genetics allows for the generation of recombinant viruses or vectors used
in functional studies, vaccine development, and gene therapy. This technique
enables genetic manipulation and cloning of viral genomes, gene mutation through
site-directed mutagenesis, along with gene insertion or deletion, among other
studies. An in vitro infection-based system including the highly attenuated
vaccinia virus Ankara strain expressing the T7 RNA polymerase from bacteriophage
T7, with co-transfection of three helper plasmids and a full-length cDNA plasmid,
was successfully developed to rescue genetically modified Newcastle disease
viruses in 1999. In this chapter, the materials and the methods involved in
rescuing Newcastle disease virus (NDV) from cDNA, utilizing site-directed
mutagenesis and gene replacement techniques, are described in detail.
PMID- 28508220
TI - Reverse Genetics Systems for Filoviruses.
AB - Filoviruses are among the most pathogenic viruses known to man. Reverse genetics
systems, in particular full-length clone systems, allow the generation of
recombinant filoviruses, which can be used to study virus biology, but also for
applied uses such as screening for countermeasures. Here we describe the
generation of recombinant filoviruses from cDNA.
PMID- 28508222
TI - Lassa Virus Reverse Genetics.
AB - The Old World (OW) arenavirus Lassa (LASV ) is estimated to infect several
hundred thousand people yearly in West Africa, resulting in high numbers of Lassa
fever (LF), a viral hemorrhagic fever (HF) disease associated with high morbidity
and mortality. To date, no licensed vaccines are available to LASV infections,
and anti-LASV drug therapy is limited to an off-label use of ribavirin (Rib) that
is only partially effective. The development of reverse genetics has provided
investigators with a novel and powerful approach for the investigation of the
molecular, cell biology, and pathogenesis of LASV. The use of cell-based LASV
minigenome (MG) systems has allowed examining the cis- and trans-acting factors
involved in genome replication and gene transcription and the identification of
novel drugable LASV targets. Likewise, it is now feasible to rescue infectious
recombinant (r)LASV entirely from cloned cDNAs containing predetermined mutations
in their genomes to investigate virus-host interactions and mechanisms of
pathogenesis, as well as to facilitate screens to identify antiviral drugs
against LASV and the implementation of novel strategies to develop live
attenuated vaccines (LAV). In this chapter we will summarize the state-of-the-art
experimental procedures for implementation of LASV reverse genetics. In addition,
we will briefly discuss some significant translational research developments that
have been made possible upon the development of LASV reverse genetics.
PMID- 28508221
TI - Rapid Reverse Genetics Systems for Rhabdoviruses: From Forward to Reverse and
Back Again.
AB - Methods to recover recombinant negative strand RNA viruses (rNSVs) from cloned
cDNAs have been significantly improved in more than two decades of NSV reverse
genetics . In particular, for non-segmented negative strand RNA viruses (NNSVs )
like rhabdoviruses , time-consuming generation of reverse genetics systems by
stitching PCR subfragments of genomic rhabdovirus cDNAs using ligase-based
conventional cloning approaches limited the number of available recombinant virus
cDNA clones. As genetic variability is considered an intrinsic feature of RNA
viruses, it is thus reasonable to conclude that reverse genetics approaches to
investigate natural virus functions and pathogenesis require improved systems
that reflect the complexity of naturally occurring wild-type viruses, and that
largely exclude adaption to cell culture conditions.In order to allow rapid
cloning of wild-type NSV genome populations into reverse genetics vector
plasmids, we developed a system in which cDNA copies of complete rhabdovirus
populations are inserted into a plasmid bank by linear-to-linear homologous
RecE/T recombination (LLHR ). Limited requirements for sequence information a
priori, high cloning efficiencies, and the possibility to directly generate
recombinant viruses from individual cDNA clones now offer novel opportunities to
combine forward genetic dissection of natural rhabdovirus populations and
downstream reverse genetics approaches.
PMID- 28508223
TI - Reverse Genetics of Influenza B Viruses.
AB - Annual influenza epidemics are caused not only by influenza A viruses but also by
influenza B viruses. Initially established for the generation of recombinant
influenza A viruses, plasmid-based reverse genetics techniques have allowed
researchers the generation of wild type and mutant viruses from full-length cDNA
copies of the influenza viral genome. These reverse genetics approaches have
allowed researchers to answer important questions on the biology of influenza
viruses by genetically engineering infectious recombinant viruses. This has
resulted in a better understanding of the molecular biology of influenza viruses,
including both viral and host factors required for genome replication and
transcription. With the ability to generate recombinant viruses containing
specific mutations in the viral genome, these reverse genetics tools have also
allowed the identification of viral and host factors involved in influenza
pathogenesis, transmissibility, host-range interactions and restrictions, and
virulence. Likewise, reverse genetics techniques have been used for the
implementation of inactivated or live-attenuated influenza vaccines and the
identification of anti-influenza drugs and their mechanism of antiviral activity.
In 2002, these reverse genetics approaches allowed also the recovery of
recombinant influenza B viruses entirely from plasmid DNA. In this chapter we
describe the cloning of influenza B/Brisbane/60/2008 viral RNAs into the
ambisense pDP-2002 plasmid and the experimental procedures for the successful
generation of recombinant influenza B viruses.
PMID- 28508224
TI - Rescue of Infectious Salmon Anemia Virus (ISAV) from Cloned cDNA.
AB - The piscine Orthomyxovirus called Infectious Salmon Anemia Virus (ISAV) is one of
the most important emerging pathogens affecting the salmon industry worldwide.
The first reverse genetics system for ISAV, which allows the generation of
recombinant ISA virus (rISAV), is an important tool for the characterization and
study of this fish virus. The plasmid-based reverse genetics system for ISAV
includes the use of a novel fish promoter, the Atlantic salmon internal
transcribed spacer region 1 (ITS-1). The salmon, viral and mammalian genetic
elements included in pSS-URG vectors allow the expression of the eight viral RNA
segments. In addition to four cytomegalovirus (CMV)-based vectors that express
the four proteins of the ISAV ribonucleoprotein complex, the eight pSS-URG
vectors allowed the generation of infectious rISAV in salmon cells.
PMID- 28508226
TI - Erratum to: Introducing precise genetic modifications into human 3PN embryos by
CRISPR/Cas-mediated genome editing.
PMID- 28508225
TI - Plasmid-Based Reverse Genetics of Influenza A Virus.
AB - Influenza A viruses have broad host range with a recognized natural reservoir in
wild aquatic birds. From this reservoir, novel strains occasionally emerge with
the potential to establish stable lineages in other avian and mammalian species,
including humans. Understanding the molecular changes that allow influenza A
viruses to change host range is essential to better assess their animal and
public health risks. Reverse genetics systems have transformed the ability to
manipulate and study negative strand RNA viruses. In the particular case of
influenza A viruses, plasmid-based reverse genetics approaches have allowed for a
better understanding of, among others, virulence, transmission, mechanisms of
antiviral resistance, and the development of alternative vaccines and vaccination
strategies. In this chapter we describe the cloning of cDNA copies of viral RNA
segments derived from a type A influenza virus into reverse genetics plasmid
vectors and the experimental procedures for the successful generation of
recombinant influenza A viruses.
PMID- 28508227
TI - The MDM2 promoter T309G polymorphism was associated with preeclampsia
susceptibility.
AB - PURPOSE: Preeclampsia (PE) is a hypertensive disorder of pregnancy in which
abnormal proliferation and apoptosis of placenta trophoblast has a pivotal role
in its pathophysiology. The aim of the current study was to examine the
association between Mouse Double Minute 2 (MDM2) T309G and 40 bp
insertion/deletion (I/D) polymorphisms and PE risk. METHODS: A case-control study
was conducted on 208 PE women and 164 healthy pregnant women matching age, sex,
and ethnicity. Polymerase chain reaction-restriction fragment length polymorphism
(PCR-RFLP) and PCR methods were used for genotyping. RESULTS: The MDM2 309GG
genotype was associated with PE, and this genotype was found to be a risk factor
for PE. There was no association between the MDM2 I/D polymorphism and PE. The
haplotype-based association analysis revealed no association between MDM2 T309G
and 40 bp I/D polymorphisms and PE. The frequency of TT-DD and GG-DD combined
genotypes were significantly higher in PE women with marginal P values (P =
0.046). CONCLUSIONS: The MDM2 309GG genotype was associated with higher risk of
PE. The TT-DD and GG-DD combined genotypes were higher in PE women.
PMID- 28508229
TI - Return to sports after ACL reconstruction: a paradigm shift from time to
function.
PMID- 28508228
TI - Relationship between white blood cell count elevation and clinical response after
G-CSF priming chemotherapy for acute myeloid leukemia.
AB - We retrospectively analyzed the relationship between white blood cell (WBC) count
elevation after priming and clinical response in 115 patients with AML (61
untreated and 54 relapsed or refractory) treated with low-dose cytarabine,
aclarubicin, and G-CSF priming. Receiver operating characteristic curve analysis
showed that the ratio of maximum WBC count to pretreatment WBC count (WBCratio)
was most strongly associated with complete remission (CR) in previously untreated
patients among several parameters we analyzed in this study; however, the
prediction accuracy was not clinically significant considering the area under the
curve of 0.694. Based on the cutoff value of the WBCratio, CR rate and event-free
survival in the high WBCratio group were significantly better than those in the
low WBCratio group in untreated patients. Regarding the WBC differential counts,
a high ratio of the maximum to pretreatment value of neutrophils rather than that
of peripheral blasts was associated with a superior CR rate. In addition, an
increase in blasts after G-CSF priming had a significant negative impact on CR
rate in untreated patients. In conclusion, an increase in blast counts after G
CSF priming was not predictive of achieving CR.
PMID- 28508230
TI - Erratum to: Exposure to di-2-ethylhexyl terephthalate in a convenience sample of
U.S. adults from 2000 to 2016.
PMID- 28508231
TI - Role of the aryl hydrocarbon receptor in carcinogenesis and potential as an anti
cancer drug target.
AB - The aryl hydrocarbon receptor (AhR) was initially identified as the receptor that
binds and mediates the toxic effects induced by 2,3,7,8-tetrachlorodibenzo-p
dioxin (TCDD) and structurally related halogenated aromatics. Other toxic
compounds including some polynuclear aromatic hydrocarbons act through the AhR;
however, during the last 25 years, it has become apparent that the AhR plays an
essential role in maintaining cellular homeostasis. Moreover, the scope of
ligands that bind the AhR includes endogenous compounds such as multiple
tryptophan metabolites, other endogenous biochemicals, pharmaceuticals and health
promoting phytochemicals including flavonoids, indole-3-carbinol and its
metabolites. It has also been shown that like other receptors, the AhR is a drug
target for multiple diseases including cancer, where both AhR agonists and
antagonists effectively block many of the critical hallmarks of cancer in
multiple tumor types. This review describes the anti-cancer activities of AhR
ligands and demonstrates that it is time to separate the AhR from TCDD and
exploit the potential of the AhR as a novel target for cancer chemotherapy.
PMID- 28508232
TI - Is Routine Prophylactic Cholecystectomy Necessary During Gastrectomy for Gastric
Cancer? Reply.
PMID- 28508233
TI - Sentinel Lymph Node Mapping with Isosulfan Blue or Indocyanine Green in Colon
Cancer Shows Comparable Results and Identifies Patients with Decreased Survival:
A Prospective Single-Center Trial.
AB - BACKGROUND: Sentinel lymph node (SLN) mapping was reported to improve lymph node
staging in colon cancer. This study compares isosulfan blue (IB) with indocyanine
green (ICG)-based SLN-mapping and assesses the prognostic value of isolated tumor
cells (ITC) and micro-metastases in upstaged patients. METHODS: A total of 220
stage I-III colon cancer patients were included in this prospective single-center
study. In 170 patients, SLN-mapping was performed in vivo with IB and in 50
patients ex vivo with ICG. Three levels of each SLN were stained with H&E. If
negative for tumor infiltration, immunostaining for cytokeratin (AE1/3;
cytokeratin-19) was performed. RESULTS: SLN detection rate for IB and ICG was 100
and 98%, respectively. Accuracy and sensitivity was 88 and 75% for IB, 82 and 64%
for ICG, respectively (p = 0.244). Overall, 149 (68%) patients were node
negative. In these patients, ITC and micro-metastases were detected in 26%
(31/129) with IB and 17% (5/29) with ICG (p = 0.469). Patients with ITC and micro
metastases did show decreased overall survival (hazard ratio = 1.96, p = 0.09)
compared to node negative disease. CONCLUSIONS: This study demonstrates a high
diagnostic accuracy for both the IB and the ICG SLN-mapping. SLN-mapping upstaged
a quarter of patients with node negative colon cancer, and the detected ITC and
micro-metastases were an independent negative prognostic marker in multivariate
analysis.
PMID- 28508234
TI - Surgical Treatment of Extraesophageal Manifestations of Gastroesophageal Reflux
Disease.
AB - OBJECTIVE: To review the current literature on the role of antireflux surgery
(ARS) for the treatment of extraesophageal manifestations of GERD. The
extraesophageal manifestations of gastroesophageal reflux disease (GERD) include
chronic cough, laryngopharyngeal reflux, and asthma. They are responsible for
significant morbidity in affected patients and a high economic burden on
healthcare resources. We recently published a larger review on the symptoms,
diagnosis, medical, and surgical treatment of the extraesophageal manifestations
of GERD. Through our investigation, we found that the role of ARS for respiratory
symptoms was unclear. Hence, we resorted through the data of our previous meta
analysis to compile a comprehensive and focused review on the role of ARS for
respiratory symptoms. METHODS: Using the archive of our previous meta-analysis,
we selected studies extracted from the MEDLINE, Cochran, PubMed, Google Scholar,
and Embase databases pertaining to the surgical treatment of extraesophageal
manifestations of reflux (cough laryngopharyngeal reflux, and asthma). We applied
a similar reporting methodology as was used in our previous manuscript and then
hand searched the bibliographies of included studies yielding a total of 27
articles for review. We graded the level of evidence and classified
recommendations by size of treatment effect per the American Heart Association
Task Force on Practice Guidelines. RESULTS: Observational data indicated that
syndromes of chronic cough, laryngopharyngeal reflux and asthma might improve
after antireflux surgery only in highly selected patients-likely those with non
acid reflux-while those patients with objective markers of asthma severity do
not. Because of the varied methods of diagnosis and surgical technique, non
comparative observational data may be unreliable. Additionally, our search found
no randomized controlled trials (RCTs) comparing antireflux surgery to medical
therapy in the treatment of cough or laryngopharyngeal reflux. One RCT compared
medical treatment to antireflux surgery in patients with asthma, but medical
treatment included high-dose H2 blockers instead of PPIs. CONCLUSIONS:
Extraesophageal manifestations of GERD are common, costly, and difficult to
treat. ARS might be effective in highly selected patients, especially in those
whose extraesophageal manifestations are caused by non-acid reflux. The available
data to date are generally of poor quality or outdated. Well-designed randomized
controlled trials or large-scale observational cohort studies are urgently
needed.
PMID- 28508235
TI - The Presence of Postoperative Infectious Complications is Associated with the
Risk of Early Postoperative Clinical Recurrence of Crohn's Disease.
AB - BACKGROUND: The purpose of the study was to identify risk factors for early
clinical and surgical recurrence in Crohn's disease (CD) patients who underwent
intestinal resection. METHOD: This was a retrospective study. Consecutive
patients who underwent intestinal resection with a primary anastomosis from
January 2011-December 2014 were enrolled. Gender, age at surgery, clinical
phenotypes of CD, serum albumin and C-reactive protein level the day before
surgery, smoking status at surgery, anastomosis technique, number of anastomoses,
details of postoperative complications, the postoperative prophylactic treatment
were assessed to figure out risk factors for postoperative clinical and surgical
recurrence within 1 year after the initial resection by univariate and then
multivariate analysis. RESULTS: Two hundred and thirty-seven patients were
analyzed. The risk of early postoperative clinical recurrence was 2.99 times
higher in patients suffered postoperative infectious complications [odds ratio
(OR) 2.99; 95% CIs, 1.42-6.32; p = 0.004], while never-smoking was found to be a
protective factor for early clinical recurrence (OR 0.326; 95% CIs, 0.18-0.59; p
< 0.0001). For surgical recurrence within 1 year after resection, the presence of
postoperative intra-abdominal septic complications might be a risk factor (OR
6.77; 95% CIs, 1.61-28.5; p = 0.009). Smoker at surgery was also a risk factor
for early surgical recurrence (OR 5.41; 95% CIs, 1.36-21.5; p = 0.017).
CONCLUSION: The presence of postoperative infectious complications was identified
as a possible risk factor for early postoperative clinical recurrence after
resection in CD patients.
PMID- 28508236
TI - An Exploratory Analysis of the Geographical Distribution of Trauma Incidents in
Shenzhen, China.
AB - BACKGROUND: The city of Shenzhen, China, is planning to establish a trauma
system. At present, there are few data on the geographical distribution of
incidents, which is key to deciding on the location of trauma centres. The aim of
this study was to perform a geographical analysis in order to inform the
development of a trauma system in Shenzhen. METHODS: Retrospective analysis of
trauma incidents attended by Shenzhen Emergency Medical Services (EMS) in 2014.
Data were obtained from Shenzhen EMS. Incident distribution was explored using
dot and kernel density estimate maps. Clustering was determined using the nearest
neighbour index. The type of healthcare facilities which patients were taken to
was compared against patients' needs, as assessed using the Field Triage Decision
Scheme. RESULTS: There were 49,082 recorded incidents. A total of 3513 were
classed as major trauma. Mapping demonstrates that incidents predominantly
occurred in the western part of Shenzhen, with identifiable clusters. Nearest
neighbour index was 0.048. Of patients deemed to have suffered major trauma, 8.5%
were taken to a teaching hospital, 13.6% to a regional hospital, 42.6% to a
community hospital, and 35.3% to a private hospital. The proportions of Step 1 or
2 negative patients were almost identical. CONCLUSION: The majority of trauma
patients, including trauma patients who are at greater likelihood of severe
injury, are taken to regional and community hospitals. There are areas with
identifiable concentrations of volume, which should be considered for the siting
of high-level trauma centres, although further modelling is required to make firm
recommendations.
PMID- 28508239
TI - Double crush syndrome caused by cervical spondylosis and vertebral artery loop.
AB - PURPOSE: The purpose of this article is to report a successful treatment
experience in a rare case of simultaneous cervical nerve root compression by
spondylotic cervical foraminal stenosis and a vertebral artery loop. METHODS: 51
year-old man presented with a 4-year history of left-sided cervical pain
radiating to the left shoulder with progressive exacerbation of weakness on left
shoulder girdle muscles for 7 months. The patient had no history of trauma. The
patient's CT and MRI revealed impingement of the left C6 cervical nerve root by a
tortuous vertebral artery loop and also by narrowed left C5-6 cervical foramen
that had undergone spondylotic changes. The patient underwent left C5-6
hemilaminectomy, facetectomy and C5-6 fusion. The procedures were uneventful, and
the patient recovered with complete resolution of symptoms. RESULTS: The patient
continued to be asymptomatic at a 2-year follow-up examination, and the muscle
mass of his left girdle returned normal. CONCLUSIONS: This report illustrates the
first phenomenon of a double crush syndrome caused by vertebral artery loop and
cervical spondylotic changes. When patients with cervical spondylosis present
with unexplainably severe pain and weakness, additional underlying pathologies
should be considered when making differential diagnoses. The investigation
planning should involve electromyography, computed tomography angiography, and
magnetic resonance imaging.
PMID- 28508238
TI - Surgical excision for recurrent herpes simplex virus 2 (HSV-2) anogenital
infection in a patient with human immunodeficiency virus (HIV).
AB - Recurrent anogenital herpes simplex virus infections are common in patients with
human immunodeficiency virus (HIV), of whom approximately 5% develop resistance
to acyclovir. We present a case of a 49-year-old man with HIV who had an 8-year
history of recurrent left inguinal herpes simplex virus type 2 ulcerations. He
initially responded to oral acyclovir, but developed resistance to acyclovir and
eventually foscarnet. The lesion progressed to a large hypertrophic mass that
required surgical excision, which led to resolution without recurrences. Our case
highlights the importance of surgical excision as a treatment option in
refractory herpes simplex virus anogenital infections.
PMID- 28508240
TI - Atlantoaxial dislocation and os odontoideum in two identical twins: perspectives
on etiology.
AB - PURPOSE: There are two theories about the origin of os odontoideum: traumatic or
congenital. However, most studies favor the hypothesis of traumatic theory. To
emphasize the congenital theory, we report a pair of identical twins both with
atlantoaxial dislocation and os odontoideum, which is believed to be a congenital
defect. METHODS: We present two 14-year-old identical twins with atlantoaxial
dislocation and os odontoideum. Neither of the twins had history of trauma in
head nor cervical spine. We reviewed and compared the cervical radiographs of the
identical twins. Posterior atlantoaxial reduction, pedicle screw fixation and
atlantoaxial fusion were performed for the two twins. RESULTS: Radiological
examination showed the identical twins had typical atlantoaxial dislocation and
os odontoideum. The twins had high similarity in the appearance of atlantoaxial
dislocation and os odontoideum. The etiology of the os odontoideum in the twins
is believed to be congenital. Both the twins had improvement in neurological
function after surgery. CONCLUSION: Although a great number of cases with os
odontoideum have been reported to be traumatic, there are some cases believed to
be congenital.
PMID- 28508241
TI - Resource Use and Real-World Outcomes for Ranibizumab Treat and Extend for
Neovascular Age-Related Macular Degeneration in the UK: Interim Results from
TERRA.
AB - INTRODUCTION: Ranibizumab is an inhibitor of vascular endothelial growth factor-A
(anti-VEGF) approved for the treatment of neovascular age-related macular
degeneration (nAMD). The treat and extend (T&E) regimen can potentially reduce
the burden of clinic visits compared with a pro re nata (PRN) regimen.
Retrospective, interim analyses of clinical effectiveness, treatment and resource
use patterns were conducted using real-world data in England and Wales from the
TERRA study. METHODS: Two cohorts, those switching from a PRN to a T&E regimen
('prior PRN') and those initiating ranibizumab on the T&E regimen as their first
anti-VEGF therapy ('anti-VEGF-naive') were enrolled in TERRA. Retrospective
clinical assessments were gathered from medical records, while resource use
patterns were collected via an operating cost questionnaire completed by each
study site. RESULTS: At the interim analysis cut-off date (15 November 2016), 11
sites had enrolled 145 patients (prior PRN: n = 110; anti-VEGF-naive: n = 35).
Mean change from baseline (date of first injection) in visual acuity and central
subfield retinal thickness to 12 months was +7.6 Early Treatment Diabetic
Retinopathy Study letters [95% confidence interval (CI) 2.8, 12.4; p = 0.003; n =
27] and -67.7 MUm (95% CI -106.5, -28.9; p = 0.001, n = 29), respectively, in the
anti-VEGF-naive cohort. Most T&E clinics were run as one-stop services (same-day
monitoring and injection), whereas 4/10 PRN clinics were run as two-stop services
(monitoring and injection on different days). In general, one-stop clinics used
less staff resources and were likely to be shorter in duration for healthcare
providers than the cumulative time spent for two-stop clinics. CONCLUSION: This
is the first real-world observational study conducted in England and Wales
demonstrating the effectiveness of the ranibizumab T&E regimen in anti-VEGF-naive
patients. T&E is compatible with one-stop clinic services, which these real-world
data suggest to be less resource intensive than two-stop clinic services,
possibly providing a dosing regimen beneficial to both patients and resource
burden in UK clinical practice. FUNDING: Novartis Pharmaceuticals UK Limited.
PMID- 28508237
TI - Development of a Unifying Target and Consensus Indicators for Global Surgical
Systems Strengthening: Proposed by the Global Alliance for Surgery, Obstetric,
Trauma, and Anaesthesia Care (The G4 Alliance).
AB - After decades on the margins of primary health care, surgical and anaesthesia
care is gaining increasing priority within the global development arena. The 2015
publications of the Disease Control Priorities third edition on Essential Surgery
and the Lancet Commission on Global Surgery created a compelling evidenced-based
argument for the fundamental role of surgery and anaesthesia within cost
effective health systems strengthening global strategy. The launch of the Global
Alliance for Surgical, Obstetric, Trauma, and Anaesthesia Care in 2015 has
further coordinated efforts to build priority for surgical care and anaesthesia.
These combined efforts culminated in the approval of a World Health Assembly
resolution recognizing the role of surgical care and anaesthesia as part of
universal health coverage. Momentum gained from these milestones highlights the
need to identify consensus goals, targets and indicators to guide policy
implementation and track progress at the national level. Through an open
consultative process that incorporated input from stakeholders from around the
globe, a global target calling for safe surgical and anaesthesia care for 80% of
the world by 2030 was proposed. In order to achieve this target, we also propose
15 consensus indicators that build on existing surgical systems metrics and
expand the ability to prioritize surgical systems strengthening around the world.
PMID- 28508242
TI - Preclinical study of a cost-effective photodynamic therapy protocol for treating
oral candidoses.
AB - Photodynamic therapy (PDT) is a promising treatment for oral candidoses. Its use
as an alternative to antifungals prevents several adverse effects, including
microbial resistance. However, most PDT protocols do not employ devices and
consumables commonly available in dental practice, thus influencing treatment
affordability. This study aimed to determine the efficacy of a PDT method based
on light curing units' blue LEDs combined to a plaque-disclosing composition (5%
erythrosine) against C. albicans in culture and in a murine model of oral
candidosis. Standard and resistant fungal strains were tested in vitro in
planktonic and biofilm forms. PDT (pre-irradiation time periods: 30 and 60 s;
irradiation time: 3 min) was compared to control conditions without light and/or
erythrosine. Mice with induced oral candidosis (n = 40) randomly received PDT or
similar control conditions with subsequent C. albicans count. These mice
underwent histological analysis, as well as 12 healthy mice submitted to
experimental treatments. PDT completely inactivated C. albicans planktonic cells
and biofilm. Control conditions presented minor differences (ANOVA, p < 0.05),
with mean values ranging from 5.2 to 6.8 log10 (UFC/mL). Infected mice presented
no significant difference in C. albicans counts consequent to treatments (ANOVA,
p = 0.721), although the PDT protocol was able to enhance the inflammatory
infiltrate in healthy mice. It can be concluded that the tested PDT protocol can
inactivate C. albicans but still needs further investigation in order to achieve
efficacy and safety.
PMID- 28508243
TI - Low-level laser treatment stimulates hair growth via upregulating Wnt10b and beta
catenin expression in C3H/HeJ mice.
AB - This study was conducted in order to evaluate the role of low-level laser
treatment (LLLT) in hair growth in C3H/HeJ mice. Healthy C57BL/6 mice were
randomly divided into two groups: with and without low-level laser treatment. The
skin color of each mouse was observed each day. Skin samples were collected for
H&E, immunofluorescence, PCR, and western blot analysis, to observe the
morphology of hair follicles and detect the expression levels of Wnt10b and beta
catenin. Observation of skin color demonstrated that black pigmentation started
significantly earlier in the laser group than in the control group. Hair follicle
number in both groups showed no difference; however, the hair follicle length
presented a significant difference. Wnt10b protein was detected on the second day
in hair matrix cells in the LLLT group but not in the control group. PCR and
western blot results both illustrated that expression of Wnt10b and beta-catenin
was significantly higher in the LLLT group than in the control group. Our study
illustrated that low-level laser treatment can promote hair regrowth by inducing
anagen phase of hair follicles via initiating the Wnt10b/beta-catenin pathway.
PMID- 28508245
TI - Evaluation of macular and peripapillary choroidal thickness, macular volume and
retinal nerve fiber layer in acromegaly patients.
AB - PURPOSE: To evaluate macular volume, retinal nerve fiber layer, and macular and
peripapillary choroidal thickness in acromegaly patients. METHOD: In this
prospective, case-control study, 31 patients with acromegaly and 32 healthy
subjects were recruited. Only right eyes were evaluated. Macular choroidal
thickness (CT) was measured at three points, peripapillary CT was measured at
eight points, and macular volume was measured at nine areas in the central 6 mm
circle zone by spectraldomain optical coherence tomography (OCT). Retinal nerve
fiber layer (RNFL) was measured automatically at six segments by OCT. RESULTS:
The mean macular and peripapillary CT at all measuring points were significantly
higher in acromegaly group (p < 0.05). RNFL thicknesses were significantly higher
in acromegaly except for temporal segment (p < 0.05). The mean total, inferior
and superior retinal volume of the macula were significantly higher in acromegaly
group (p < 0.001), whereas there was no statistically difference was seen in
retinal volume of temporal and nasal macular area between the two groups (p >
0.05). CONCLUSION: The macular and peripapillary choroidal thickness, retinal
nerve fiber layer, and total retinal volume of the macula were significantly
higher in acromegaly patients. Increased choroidal thickness may cause different
macular pathologies such as choroidal neovascularization. RNFL results may be
important in acromegaly patients with glaucoma, especially if the progress of
glaucoma is monitored by OCT.
PMID- 28508244
TI - Interventions for the endodontic management of non-vital traumatised immature
permanent anterior teeth in children and adolescents: a systematic review of the
evidence and guidelines of the European Academy of Paediatric Dentistry.
AB - AIM: This systematic review was undertaken in order to develop guidelines for the
European Academy of Paediatric Dentistry for the management of non-vital
permanent anterior teeth with incomplete root development. METHODS: Three
techniques were considered; apexification by single or multiple applications of
calcium hydroxide, use of Mineral Trioxide Aggregate (MTA) for the creation of an
apical plug followed by obturation of the root canal, and finally a Regenerative
Endodontic Technique (RET). Scottish Intercollegiate Guideline Network (SIGN)
Guidelines (2008) were used for the synthesis of evidence and grade of
recommendation. RESULTS: Variable levels of evidence were found and generally
evidence related to these areas was found to be weak and of low quality. It was
not possible to produce evidence-based guidelines based on the strength of
evidence that is currently available for the management of non-vital immature
permanent incisors. CONCLUSIONS: Based on the available evidence the European
Academy of Paediatric Dentistry proposes Good Clinical Practice Points as a
guideline for the management of such teeth. It is proposed that the long term use
of calcium hydroxide in the root canals of immature teeth should be avoided and
apexification with calcium hydroxide is no longer advocated. The evidence related
to the use of a Regenerative Endodontic Technique is currently extremely weak and
therefore this technique should only be used in very limited situations where the
prognosis with other techniques is deemed to be extremely poor. The current
review supports the use of MTA followed by root canal obturation as the treatment
of choice.
PMID- 28508246
TI - The significance of histological analysis following laser transurethral resection
of the prostate.
AB - PURPOSE: Monopolar transurethral resection of the prostate is the gold standard
for the treatment of benign prostatic hyperplasia. However, due to the associated
risks of bleeding and TUR syndrome, laser prostate surgery is gaining popularity.
We perform thulium-laser vaporesection of the prostate (TmLRP), where
histological samples are generated in every case. We determined postoperative
incidence and significance of prostate cancer detection, by retrospective
histological examination of our cases. METHODOLOGY: Between October 2006 and
August 2012, 223 patients underwent TmLRP by a single surgeon in our institution.
With a background of a benign DRE, and no suspicion of CaP, histological results
were studied. RESULTS: Mean age was 71 years (range 46-91), mean PSA was 4.1
ng/mL (range 0.1-20). 4.9% (11/223) had cancer prostate (CaP) diagnosed, with
mean PSA of 6.9 ng/mL (range 0.7-14). Of these: 91% (10/11) had pT1b disease
while 9% (1/11) had pT1a disease. Gleason score was 6 in 28% (3/11); 7 in 36%
(4/11); 8 in 18% (2/11); 9 in and 18% (2/11). CONCLUSION: 4.9% of patients had
unexpected CaP, with significant disease in 4.4% (pT1b) and 3.6% (Gleason score
>=7). Hence, patients should be advised of the small risk of missing significant
unsuspected CaP after laser prostatectomy.
PMID- 28508248
TI - Endogenous versus exogenous generic reference pricing for pharmaceuticals.
AB - In this paper we carry out a vertical differentiation duopoly model applied to
pharmaceutical markets to analyze how endogenous and exogenous generic reference
pricing influence competition between generic and branded drugs producers. Unlike
the literature, we characterize for the exogenous case the equilibrium prices for
all feasible relevant reference prices. Competition is enhanced after the
introduction of a reference pricing system. We also compare both reference
pricing systems on welfare grounds, assuming two different objective functions
for health authorities: (i) standard social welfare and (ii) gross consumer
surplus net of total pharmaceutical expenditures. We show that regardless of the
objective function, health authorities will never choose endogenous reference
pricing. When health authorities are paternalistic, the exogenous reference price
that maximizes standard social welfare is such that the price of the generic drug
is the reference price while the price of the branded drug is higher than the
reference price. When health authorities are not paternalistic, the optimal
exogenous reference price is such that the price of the branded drug is the
reference price while the price of the generic drug is lower than the reference
price.
PMID- 28508247
TI - In human cell cultures, everolimus is inferior to tacrolimus in inhibiting
cellular alloimmunity, but equally effective as regards humoral alloimmunity.
AB - PURPOSE: Acute cellular rejection is the major cause of immune-mediated graft
failure early in the course of kidney transplantation, whereas chronic antibody
mediated rejection is a major contributor to graft loss in the late post
transplant phase. Based mainly on the results of short-term studies, the
calcineurin inhibitor tacrolimus prevails over the mammalian target of rapamycin
(mTOR) inhibitors. However, the toxicity profile of the two drug categories
differs, making the interchange between them appealing. In this study, the effect
of tacrolimus and of the mTOR inhibitor everolimus on cellular and humoral
alloimmunity was evaluated. METHODS: Cellular alloimmunity was assessed by cell
proliferation in two-way mixed lymphocyte reaction (MLR) with human peripheral
blood mononuclear cells (PBMC). For assessing humoral alloimmunity, we developed
a method in which humoral alloimmunity was induced in a one-way MLR. The de novo
production of alloantibodies was measured with an antibody-mediated complement
dependent cytotoxicity assay, in which supernatants from the above MLRs were used
against resting PBMC similar to the stimulator cells of the forementioned MLRs.
Tacrolimus and everolimus were used at concentrations near their upper
recommended trough levels. RESULTS: In two-way MLRs, tacrolimus inhibited cell
proliferation more than everolimus. In one-way MLRs, tacrolimus and everolimus
decreased alloantibody production to the same extent. CONCLUSIONS: In human cell
cultures, everolimus is inferior to tacrolimus in inhibiting cellular
alloimmunity, but equally effective as regards humoral alloimmunity. Thus,
everolimus might be a safe alternative in case of tacrolimus toxicity,
particularly after the early period of kidney transplantation.
PMID- 28508249
TI - Self- and Peer-Identified Victims in Late Childhood: Differences in Perceptions
of the School Ecology.
AB - Patterns of adjustment for youth victimized by peers vary depending on whether
youth are identified as victims through self-reports, peer-reports, or both. In
order to provide more targeted strategies that may help mitigate negative
consequences associated with specific victimization groups, more information is
needed about how these youth perceive their school ecology (bullying and academic
ecology), their feelings of school belonging, and their valuing of school. Based
on the convergence of self- and peer-reports of victimization, we identified four
victim groups from a sample of students in 5th grade classrooms (N = 1360; 52.8%
girls, 53.1% White, 34.6% Black or Hispanic, 12.2% Native American, Asian, or
other) using Latent Profile Analysis (LPA): convergent victims (high self- and
peer-reports), self-identified victims (high self-, low peer-reports), peer
identified victims (low self-, high peer-reports), and nonvictims (low self- and
peer-reports). Convergent victims' perceptions were similar to nonvictims with
key differences being convergent victims' greater willingness to protect peers
being bullied but lower feelings of school belonging compared to nonvictims. Peer
identified and self-identified victims perceived differences in the bullying and
academic ecology including peer-identified victims' greater willingness to
protect peers and expectations for more peers to encourage bulling against them
compared to self-identified victims. However, both peer- and self-identified
victims perceived greater emotional risk of participating in class and had lower
feelings of school belonging compared to nonvictims. Implications for supporting
youth with divergent self- and peer-reported victimization status as they
transition to middle school are discussed.
PMID- 28508250
TI - A Real-world Analysis of Treatment Patterns for Cholinesterase Inhibitors and
Memantine among Newly-diagnosed Alzheimer's Disease Patients.
AB - INTRODUCTION: Alzheimer's disease (AD) is the most common neurodegenerative form
of dementia. Pharmacological therapies for symptomatic treatment, such as
acetylcholinesterase inhibitors (AChEIs) and memantine, have been available in
the USA since 2000. Over the past decade, few studies have analyzed real-world
anti-dementia treatment patterns in the USA. This study evaluated monotherapy
AChEIs and memantine treatment patterns among newly diagnosed AD patients.
METHODS: A retrospective cohort study was conducted using Medicare data and the
Minimum Data Set from 2008 to 2012. Patients aged 65-100 years with newly
diagnosed AD (ICD-9 code: 331.0) and monotherapy AChEI or memantine treatment
initiated after diagnosis were included. Descriptive treatment pattern analyses,
including discontinuation and switch, were undertaken. Kaplan-Meier curves were
developed to examine the treatment duration. RESULTS: A total of 9812 newly
diagnosed AD patients were identified, with 56.7% (n = 5567) first receiving anti
dementia treatment after the initial AD diagnosis. Among patients initiating
monotherapy AChEIs or memantine after AD diagnosis (N = 5200), 51.6% continued
index treatment during the entire follow-up period (mean follow-up: 659.7 days)
and 21.7% discontinued treatment. Of those who initiated monotherapy treatment
with an AChEI, 11.1% received adjunct therapy with memantine. Among patients with
>=1 year of continuous treatment (mean follow-up: 834 days), 75.6% remained on
the index drug, 10.2% discontinued during the remaining follow-up period, and
9.5% of the AD patients initiating AChEIs received adjunct memantine therapy
during the remaining follow-up period. CONCLUSION: In the USA Medicare
population, about 50% of the patients who initiated treatment with AChEI or
memantine after diagnosis continued the index treatment, and more than 20%
discontinued and were untreated afterwards over the observation period. AD
patients initiating AChEIs or memantine were more likely to remain on their
treatment if they were persistently treated for the first year.
PMID- 28508251
TI - Occlusion of a Long-Term Transpleural Biliary Drainage Tract Using a Gelatin
Pledget (Hep-PlugTM).
AB - This case describes a technique used to close a long-term 14F transpleural
biliary drainage catheter tract to prevent biliopleural fistula and further
complications. We deployed a compressed gelatin foam pledget provided in a pre
loaded delivery device (Hep-PlugTM) along the intrahepatic tissue tract for
sealing it against the pleural cavity. The device used is easy to handle and
gives the Interventional Radiologist the possibility to safely manage and prevent
complications after percutaneous transhepatic interventions.
PMID- 28508252
TI - Anatomical Variants in Prostate Artery Embolization: A Pictorial Essay.
AB - Prostate artery embolization (PAE) has emerged as a new treatment option for
patients with symptomatic benign prostatic hyperplasia. The main challenges
related to this procedure are navigating arteries with atherosclerosis and
anatomical variations, and the potential risk of non-target embolization to
pelvic structures due to the presence of collateral shunts and reflux of
microparticles. Knowledge of classical vascular anatomy and the most common
variations is essential for safe embolization, good clinical practice, and
optimal outcomes. The aim of this pictorial essay is to illustrate the pelvic
vascular anatomy relevant to PAE in order to provide a practical guide that
includes the most common anatomical variants as well as to discuss the technical
details related to each.
PMID- 28508253
TI - Image-Guided Transarterial Chemoembolization With Drug-Eluting Beads Loaded with
Doxorubicin (DEBDOX) for Unresectable Hepatic Metastases from Melanoma: Technique
and Outcomes.
AB - PURPOSE: Hepatic metastasis from melanoma represents a therapeutic dilemma, with
limited effective options for the 85% of cases deemed unresectable. Systemic
agents confer toxicity and, along with traditional local hepatic arterial
directed therapies such as transarterial chemoembolization, have not led to a
significant increase in survival. The aim of this study was to investigate the
safety and dose-limiting toxicity of DEBDOX for the treatment of unresectable
hepatic metastases from melanoma. METHODS: A multicenter (University of
Louisville, Thomas Jefferson University, MD Anderson Cancer Center), prospective,
non-controlled treatment trial (NCT01010984) of hepatic-directed therapy with
DEBDOX for the treatment of melanoma liver metastasis was reviewed. Primary
endpoints were response rates by modified response evaluation criteria in solid
tumors, hepatic progression-free survival (PFS), and overall survival (OS).
RESULTS: Twenty patients received a total of 61 DEBDOX treatments from January
2010 to March 2013. The median hepatic tumor burden was 40% (range 20-55), 18
patients (90%) had bilobar disease, and 13 patients (65%) had concomitant
extrahepatic disease. At median assessment of 2.5 months, 11 patients (55%)
exhibited a tumor response and 16 (80%) exhibited disease control. Median follow
up was 5 months (range 1.1-34.3 months). Median hepatic PFS was 3 months (95% CI
1.4, 3.4), and OS was 5 months (95% CI 3.3, 10.5). CONCLUSIONS: Directed arterial
therapy with DEBDOX is effective in managing unresectable liver-dominant
metastasis from melanoma and should be considered a therapeutic option in the
multidisciplinary treatment of this disease. Concurrent systemic therapy is
merited given the high rate of extrahepatic progression. CLINICAL TRIAL:
NCT01010984.
PMID- 28508254
TI - Comparison of Pain Within 24 h after Uterine Artery Embolization with Tris-Acryl
Gelatin Microspheres Versus Gelatin Sponge Particles for Leiomyoma.
AB - PURPOSE: To compare acute pain after uterine artery embolization (UAE) with tris
acryl gelatin microspheres (TAGM) versus gelatin sponge particles (GS) for
leiomyoma. MATERIALS AND METHODS: This was a single-institution, retrospective
study. Between July 2008 and November 2016, 101 consecutive patients with
symptomatic uterine leiomyoma underwent UAE with the same protocol for post
procedural pain. GS was employed with near-stasis endpoint for the first 49
patients, whereas TAGM was used with limited endpoint for the next 52 patients.
Post-UAE pain levels were compared between both groups with a linear mixed model
using visual analog scale (VAS) scores from 0 to 18 h as a repeat measure
outcome. Peak VAS < 24 h or dose of drugs for analgesia and conscious sedation
was compared by analysis of variance. Tumor infarction was assessed with post
procedural contrast-enhanced MRI. RESULTS: Baseline demographics and most
outcomes including tumor infarction were similar between both groups. The average
VAS scores during the period <24 h were significantly lower in TAGM group (1.68,
95% CI 1.23-2.13) compared to GS group (3.28, 95% CI 2.82-3.74, p < 0.0001). The
difference remained significant even after adjustment for other factors (p <
0.0001). The mean peak VAS < 24 h was also lower in TAGM group (3.89, 95% CI 3.25
4.53) than in GS group (5.90, 95% CI 5.20-6.53, p < 0.0001). The dose of drugs
for analgesia and conscious sedation was significantly lower in TAGM group (p =
0.001, p = 0.004, respectively). CONCLUSION: TAGM had an advantage over GS in UAE
for leiomyoma in terms of less post-procedural pain <24 h, with lower doses of
drugs for analgesia and conscious sedation.
PMID- 28508255
TI - Psychosocial Patient-Reported Outcomes in Pediatric and Adolescent Diabetes: a
Review and Case Example.
AB - PURPOSE OF REVIEW: The purpose of this review is to define psychosocial patient
reported outcomes (PROs) relevant to pediatric and adolescent diabetes
populations. Potential domains for PROs include a spectrum of emotional,
behavioral, social, physical, overall health, and/or care management areas. A
literature review of potential PRO measures, selection criteria, and
implementation strategies including a case example will be presented. RECENT
FINDINGS: Among the pediatric, adolescent, and emerging adult populations,
research indicates a relative higher risk for distress, depression, anxiety, and
eating disorders as compared to peers without diabetes. Use of PRO measures can
expand providers' focus beyond glycemic control, or simply hemoglobin A1c, to
better appreciate the impact of diabetes on the whole child/adolescent, and
provide services that address patients' individually identified needs, which are
most salient to them. Successful selection and implementation of psychosocial PRO
measures should be designed to include pathways for real-time provider
interaction with the patient and respective PRO data to guide clinical care.
PMID- 28508257
TI - Diagnosing Allergic Contact Dermatitis Through Elimination, Perception, Detection
and Deduction.
AB - Several authors have commented upon the skills of detection required in making a
diagnosis of allergic contact dermatitis. Here, we emphasise the search for clues
in a systematic manner. We describe four stages as part of a systematic method
for diagnosing allergic contact dermatitis. Firstly, elimination (or inclusion)
of non-allergic diagnoses. Secondly, perception: the pre-patch test diagnosis and
the 'three scenarios' principle. Thirdly, detection: optimising the sensitivity
of the patch test process. Fourthly, deduction: diagnosing allergic contact
dermatitis by associating the dermatitis with the allergen exposure. We further
compare and contrast the pre-patch test history and examination with the markedly
different one ('microhistory' and 'microexamination') used after patch testing.
The importance of knowledge of contact dermatitis literature is emphasised with a
review of recent publications. Finally, we also highlight the use of contact
allergy profiling as an investigative tool in the diagnosis of allergic contact
dermatitis.
PMID- 28508256
TI - The Role of Micronutrients in Alopecia Areata: A Review.
AB - Alopecia areata (AA) is a common, non-scarring form of hair loss caused by immune
mediated attack of the hair follicle. As with other immune-mediated diseases, a
complex interplay between environment and genetics is thought to lead to the
development of AA. Deficiency of micronutrients such as vitamins and minerals may
represent a modifiable risk factor associated with development of AA. Given the
role of these micronutrients in normal hair follicle development and in immune
cell function, a growing number of investigations have sought to determine
whether serum levels of these nutrients might differ in AA patients, and whether
supplementation of these nutrients might represent a therapeutic option for AA.
While current treatment often relies on invasive steroid injections or
immunomodulating agents with potentially harmful side effects, therapy by
micronutrient supplementation, whether as a primary modality or as adjunctive
treatment, could offer a promising low-risk alternative. However, our review
highlights a need for further research in this area, given that the current body
of literature largely consists of small case-control studies and case reports,
which preclude any definite conclusions for a role of micronutrients in AA. In
this comprehensive review of the current literature, we found that serum vitamin
D, zinc, and folate levels tend to be lower in patients with AA as compared to
controls. Evidence is conflicting or insufficient to suggest differences in
levels of iron, vitamin B12, copper, magnesium, or selenium. A small number of
studies suggest that vitamin A levels may modify the disease. Though
understanding of the role for micronutrients in AA is growing, definitive
clinical recommendations such as routine serum level testing or therapeutic
supplementation call for additional studies in larger populations and with a
prospective design.
PMID- 28508258
TI - Spatiotemporal analysis the precipitation extremes affecting rice yield in
Jiangsu province, southeast China.
AB - With the increasing risk of meteorological disasters, it is of great importance
to analyze the spatiotemporal changes of precipitation extremes and its possible
impact on rice productivity, especially in Jiangsu province, southeast China. In
this study, we explored the relationships between rice yield and extreme
precipitation indices using Mann-Kendall trend test, Pettitt's test, and K-means
clustering methods. This study used 10 extreme precipitation indices of the rice
growing season (May to October) based on the daily precipitation records and rice
yield data at 52 meteorological stations during 1961-2012 in Jiangsu province.
The main findings were as follows: (1) correlation results indicated that
precipitation extremes occurred in the months of July, August, and October, which
had noticeable adverse effects on rice yield; (2) the maximum 7-day precipitation
of July and the number of rainy days of August and October should be considered
as three key indicators for the precipitation-induced rice meteorological
disasters; and (3) most of the stations showed an increasing trends for the
maximum 7-day precipitation of July and the number of rainy days of August, while
the number of rainy days of October in all the stations demonstrated a decreasing
trend. Moreover, Jiangsu province could be divided into two major sub-regions
such as north and south areas with different temporal variations in the three key
indicators.
PMID- 28508259
TI - Investigation of the scaling characteristics of LANDSAT temperature and
vegetation data: a wavelet-based approach.
AB - An investigation of the scaling characteristics of vegetation and temperature
data derived from LANDSAT data was undertaken for a heterogeneous area in Tamil
Nadu, India. A wavelet-based multiresolution technique decomposed the data into
large-scale mean vegetation and temperature fields and fluctuations in
horizontal, diagonal, and vertical directions at hierarchical spatial
resolutions. In this approach, the wavelet coefficients were used to investigate
whether the normalized difference vegetation index (NDVI) and land surface
temperature (LST) fields exhibited self-similar scaling behaviour. In this study,
l-moments were used instead of conventional simple moments to understand scaling
behaviour. Using the first six moments of the wavelet coefficients through five
levels of dyadic decomposition, the NDVI data were shown to be statistically self
similar, with a slope of approximately -0.45 in each of the horizontal, vertical,
and diagonal directions of the image, over scales ranging from 30 to 960 m. The
temperature data were also shown to exhibit self-similarity with slopes ranging
from -0.25 in the diagonal direction to -0.20 in the vertical direction over the
same scales. These findings can help develop appropriate up- and down-scaling
schemes of remotely sensed NDVI and LST data for various hydrologic and
environmental modelling applications. A sensitivity analysis was also undertaken
to understand the effect of mother wavelets on the scaling characteristics of LST
and NDVI images.
PMID- 28508260
TI - Sarcoidosis in Israel: Clinical Outcome Status, Organ Involvement, and Long-Term
Follow-Up.
AB - PURPOSE: Sarcoidosis is a chronic granulomatous inflammatory disease of unknown
etiology with heterogeneous outcomes. This study reviewed the clinical outcome
status (COS) and organ involvement of Israeli sarcoidosis patients during a five
year period. Further, we compared our results to the 'World Association of
Sarcoidosis and Other Granulomatous Disease' (WASOG) COS and the 'A Case Control
Etiologic Study of Sarcoidosis' (ACCESS) instruments in order to evaluate their
relevance to the Israeli population. METHODS: The retrospective study group
consisted of 166 sarcoidosis patients for the period of 2010-2015. Data on
demographic characteristics, presenting symptoms, co-morbidities, disease
duration, lung function tests, treatment program, chest X-ray, and chest high
resolution computed tomography were collected. RESULTS: The median patient age
was 62 +/- 14, which was significantly higher than the WASOG and ACCESS cohorts
(p < 0.0001), and the average disease duration was 9.8 +/- 7.5 years. Resembling
the ACCESS cohort, most patients were women (67.5%). The majority of patients
suffered from constitutional symptoms (86%), as well as from respiratory symptoms
(38.5%). Similarly to the ACCESS cohort, 91% of patients presented with lung
involvement. However, significant differences in the involvement of other organs
were noted, including lymph nodes (3 vs. 15.2%), liver (3.6 vs. 11.5%), CNS (7.2
vs. 4.6%), and joints (3.6 vs. 0.5%). In addition, significant differences were
observed in the COS of the Israeli population in comparison to the WASOG data (p
< 0.01). CONCLUSIONS: Sarcoidosis in Israel is a unique and challenging disease
with its clinical presentations that differ from previously reported studies.
PMID- 28508262
TI - ?
PMID- 28508263
TI - New Insights into the Anatomy of the Midface Musculature and its Implications on
the Nasolabial Fold.
AB - BACKGROUND: The prominent nasolabial fold is a distinct feature of the aging
midface. As minimally invasive procedures have become mainstream,
chemodenervation is a preferred method for treating dynamic facial rhytids. We
therefore sought to identify relevant nasolabial fold and midfacial muscular
anatomy to determine the ideal location of neuromodulation to improve the
aesthetics of the midface and nasolabial fold without altering the upper lip and
smile. METHODS: Twelve hemifacial cadaveric dissections were performed to
identify midface muscle origin, insertion, width, vector of pull, and neighboring
structures. Attention was focused on the levator labii superioris alaeque nasi
(LLSAN), levator labii superioris (LLS), nasalis, and orbicularis oculi.
Measurements were obtained based on surface landmarks including the medial
canthus for future neurotoxin injection. RESULTS: The LLSAN inserts into the
medial nasolabial fold and alar base, while the LLS inserts into the middle third
of the nasolabial fold. The broadest portion of the superior LLSAN was on average
8.4 mm inferior and 4.6 mm medial to the medial canthus. A separate muscle
obliquely oriented between the orbicularis oculi and LLSAN was identified and
found to insert into the malar fat pad. This "malar levator" was present in all
specimens and has implications on medial periorbital rhytids and the tear trough
deformity. CONCLUSION: This study further defines midfacial and nasolabial fold
muscular anatomy and provides new insights into the use of neuromodulators for
these areas without affecting upper lip position. The malar levator muscle
appears to be a separate midfacial muscle with independent action. LEVEL OF
EVIDENCE V: This journal requires that authors assign a level of evidence to each
article. For a full description of these Evidence-Based Medicine ratings, please
refer to the Table of Contents or the online Instructions to Authors
www.springer.com/00266 .
PMID- 28508261
TI - Functional roles of the pepper leucine-rich repeat protein and its interactions
with pathogenesis-related and hypersensitive-induced proteins in plant cell death
and immunity.
AB - MAIN CONCLUSION: Pepper leucine-rich repeat protein (CaLRR1) interacts with
defense response proteins to regulate plant cell death and immunity. This review
highlights the current understanding of the molecular functions of CaLRR1 and its
interactor proteins. Plant cell death and immune responses to microbial pathogens
are controlled by complex and tightly regulated molecular signaling networks.
Xanthomonas campestris pv. vesicatoria (Xcv)-inducible pepper (Capsicum annuum)
leucine-rich repeat protein 1 (CaLRR1) serves as a molecular marker for plant
cell death and immunity signaling. In this review, we discuss recent advances in
elucidating the functional roles of CaLRR1 and its interacting plant proteins,
and understanding how they are involved in the cell death and defense responses.
CaLRR1 physically interacts with pepper pathogenesis-related proteins (CaPR10 and
CaPR4b) and hypersensitive-induced reaction protein (CaHIR1) to regulate plant
cell death and defense responses. CaLRR1 is produced in the cytoplasm and
trafficked to the extracellular matrix. CaLRR1 binds to CaPR10 in the cytoplasm
and CaPR4b and CaHIR1 at the plasma membrane. CaLRR1 synergistically accelerates
CaPR10-triggered hypersensitive cell death, but negatively regulates CaPR4b- and
CaHIR1-triggered cell death. CaHIR1 interacts with Xcv filamentous hemagglutinin
(Fha1) to trigger disease-associated cell death. The subcellular localization and
cellular function of these CaLRR1 interactors during plant cell death and defense
responses were elucidated by Agrobacterium-mediated transient expression, virus
induced gene silencing, and transgenic overexpression studies. CaPR10, CaPR4b,
and CaHIR1 positively regulate defense signaling mediated by salicylic acid and
reactive oxygen species, thereby activating hypersensitive cell death and disease
resistance. A comprehensive understanding of the molecular functions of CaLRR1
and its interacting protein partners in cell death and defense responses will
provide valuable information for the molecular genetics of plant disease
resistance, which could be exploited as a sustainable disease management
strategy.
PMID- 28508264
TI - Biological Safety of a Highly Purified 10% Liquid Intravenous Immunoglobulin
Preparation from Human Plasma.
AB - BACKGROUND: A highly purified 10% liquid intravenous immunoglobulin, IQYMUNE(r),
has been developed using an innovative manufacturing process including an
affinity chromatography step for the removal of anti-A and anti-B hemagglutinins.
OBJECTIVES: The pathogen (viruses and prions) clearance efficacy of the
manufacturing process and its robustness for critical steps were investigated.
METHODS: The manufacturing process of IQYMUNE(r) includes two dedicated
complementary virus reduction steps: solvent/detergent (S/D) treatment and 20 nm
nanofiltration as well as two contributing steps, namely caprylic acid
fractionation and anion-exchange chromatography. The clearance capacity and
robustness of these steps were evaluated with a wide range of viruses (enveloped
and non-enveloped) and with a model of human transmissible spongiform
encephalopathies (TSEs). RESULTS: The IQYMUNE(r) manufacturing process
demonstrated a high and robust virus removal capacity with global reduction
factors (RFs) of relevant and model viruses: >=14.8 log10 for human
immunodeficiency virus type 1 (HIV-1), >=16.9 log10 for bovine viral diarrhoea
virus (BVDV)/Sindbis virus, >=15.7 log10 for pseudorabies virus (PRV), >=12.8
log10 for encephalomyocarditis virus (EMCV) and 11.0 log10 for porcine parvovirus
(PPV). The process also exhibited a high removal capacity for the TSE agent with
an overall RF of >=12.9 log10 due to the complementary actions of the caprylic
acid fractionation, anion-exchange chromatography and nanofiltration steps.
CONCLUSION: Data from virus and prion clearance studies fully support the high
safety profile of IQYMUNE(r), with a minimal reduction of 11 log10 for the
smallest and most resistant non-enveloped virus, PPV, and more than 12 log10 for
the TSE agent.
PMID- 28508265
TI - Incidence of Vertebral Fractures in Women with Systemic Lupus Erythematosus After
8 Years of Follow-Up.
AB - The aim of this study was to evaluate possible associations between potential
risk factors and the occurrence of established vertebral fractures (VF) in
Mexican patients with systemic lupus erythematosus (SLE). Consecutive patients
with SLE were enrolled in a prospective, observational study from 2006 to 2015.
Information on potential risk factors, including demographics, clinical data, and
bone mineral density (BMD) at the lumbar spine and hip on dual-energy X-ray
absorptiometry was collected at baseline and follow-up. Semiquantitative analysis
was used to determine incident VF on lateral thoracic and lumbar radiographs,
defined as any vertebral body graded normal at baseline and at least mildly
deformed (20-25% reduction or more in any vertebral height) during follow-up.
Differences in baseline characteristics were assessed in patients with and
without new radiographic VF. Of 110 SLE patients included, with a median follow
up of 8 (IQR 8-9) years, 22 (20%) had radiographic VF at baseline; 35 (32%)
patients had a new VF. The annual incidence rate of new morphometric VF was 3.5
(95% CI 2.4-4.91) per 100 patient/years. Most fractures were mild or moderate and
biconcave shaped. Incident VF were significantly associated with baseline BMD at
the total hip and longer disease duration. Cumulative glucocorticoid dose,
postmenopausal status, and previous prevalent VF were not associated with VF. In
this SLE cohort in daily clinical practice, new VF were frequently present in SLE
patients, especially those with longer disease duration and low-hip BMD.
PMID- 28508266
TI - The combined association of alcohol consumption with dementia risk is likely
biased due to lacking account of death cases.
PMID- 28508267
TI - Will it be cheese, bologna, or peanut butter?
PMID- 28508268
TI - Regadenoson stress during low-level exercise: The EXERRT trial-does it move the
needle?
PMID- 28508269
TI - Erratum to: Guidelines in review: Comparison between AHA/ACC and ESC guidelines
for the management of patients with ventricular arrhythmias and the prevention of
sudden cardiac death.
PMID- 28508270
TI - The impact of combined cardiopulmonary exercise testing and SPECT myocardial
perfusion imaging on downstream evaluation and management.
AB - OBJECTIVE: The diagnostic yield of combined cardiopulmonary exercise testing
(CPET) and myocardial perfusion imaging (MPI) in patients referred for stress
testing has received limited study. METHODS: We evaluated consecutive patients
who underwent combined CPET-MPI at a single tertiary referral center between 2011
and 2015. An abnormal CPET was defined as any of the following: reduced oxygen
consumption, cardiac output impairment, or pulmonary impairment. Normal MPI was
defined as the absence of resting or stress perfusion defect. The primary study
outcome was change in clinical decision-making after CPET-MPI including
management of pulmonary disease, management of deconditioning, heart failure
management, and referral for cardiac catheterization. Outcomes of patients with
normal and abnormal MPI were presented based on the specific CPET abnormality.
RESULTS: 415 patients were included in the study. Of the 269 patients that had
normal MPI, 206 (77%) had abnormal CPET. Patients with abnormal CPET and normal
MPI, compared with patients that had normal CPET and normal MPI, were more
frequently diagnosed with pulmonary disease (11.7% vs 3.2%, P = .04) and
deconditioning (33.5% vs 17.4%, P = .01). Of the 146 patients that had abnormal
MPI, 128 (88%) had abnormal CPET. Patients with abnormal CPET and abnormal MPI,
compared with patients that had normal CPET and abnormal MPI, did not
statistically differ with regard to the study outcome. CONCLUSION: An abnormal
CPET, if the MPI was normal, prompted further evaluation and led to management of
pulmonary disease and deconditioning.
PMID- 28508271
TI - Optimization of temporal sampling for 82rubidium PET myocardial blood flow
quantification.
AB - BACKGROUND: Suboptimal temporal sampling of left ventricular (LV) blood pool and
tissue time-activity curves (TACs) may introduce bias and increased variability
in estimates of myocardial blood flow (MBF) and flow reserve (MFR) from dynamic
PET myocardial perfusion images. We aimed to optimize temporal sampling for
estimation of MBF and MFR. METHODS: Twenty-four normal volunteers and 32 patients
underwent dynamic stress/rest rubidium-82 chloride (82Rb) PET imaging. Fine
temporal sampling was used to estimate the full width at half maximum (FWHM) of
the LV blood pool TAC. Fourier analysis was used to determine the longest
sampling interval, T S, as a function of FWHM, which preserved the information
content of the blood phase. Dynamic datasets were reconstructed with frame
durations varying from 2 to 20 seconds over the first 2 minutes for the blood
phase and 30 to 120 seconds for the tissue phase. The LV blood pool and tissue
TACs were sampled using regions of interest (ROI) and fit to a compartment model
for quantification of MBF and MFR. The effects of temporal sampling on MBF and
MFR were evaluated using clinical data and simulations. RESULTS: T S increased
linearly with input function FWHM (R = 0.93). Increasing the blood phase frame
duration from 5 to 15 seconds resulted in MBF and MFR biases of 6-12% and
increased variability of 14-24%. Frame durations <5 seconds had biases of less
than 5% for both MBF and MFR values. Increasing the tissue phase frame durations
from 30 to 120 seconds resulted in <5% biases. CONCLUSIONS: A two-phase framing
of dynamic 82Rb PET images with frame durations of 5 seconds (blood phase) and
120 seconds (tissue phase) optimally samples the blood pool TAC for modern 3D PET
systems.
PMID- 28508272
TI - Nasopharyngeal Angiofibroma: A Clinical, Histopathological and
Immunohistochemical Study of 42 Cases with Emphasis on Stromal Features.
AB - Nasopharyngeal angiofibroma is a benign but aggressive tumor of unknown etiology,
typically occurring in adolescent males. It is described as a rare neoplasm;
however, the prevalence seems to have geographic differences. All cases referred
to our head and neck clinical and pathology service were reviewed. Most of the
patients presented at an advanced stage. The clinical and radiographic features
are presented and discussed. Histologically, the tumor shows a highly vascular
fibrous proliferation with characteristic plump, angulated and stellate cells,
categorized as fibroblasts. Immunohistochemistry was performed on 42 cases to
further elucidate the nature of these cells. The stromal cells expressed vimentin
and factor XIIIa, the latter expressed most commonly in the giant stellate cells.
Inflammation was almost exclusively present in peripheral subepithelial areas.
Mast cells were abundant, even in the absence of other inflammatory cells.
Lymphatics were observed principally in peripheral regions. Proliferating cells
(Ki-67 reactive) were restricted to endothelial cells.
PMID- 28508274
TI - The Sleeping Remnant. Effect of Roux-En-Y Gastric Bypass on Plasma Levels of
Gastric Biomarkers in Morbidly Obese Women: A Prospective Longitudinal Study.
AB - BACKGROUND: Morpho-functional modifications of the gastric remnant after Roux-en
Y gastric bypass (RYGB) have not been completely defined, due to its
inaccessibility for bioptic mapping. The aim of the study is to evaluate such
modifications using Gastropanel(r), a non-invasive blood test cross-checking four
gastric biomarkers, able to provide a snapshot of mucosa conditions. SUBJECTS AND
METHODS: Twenty-four women undergoing RYGB were prospectively enrolled.
Gastropanel(r) parameters (pepsinogens, Gastrin-17 and immunoglobulins against
Helicobacter pylori), biometrical/clinical data were collected preoperatively and
at 6-months follow-up. RESULTS: All parameters showed significant reduction (p <
0.05). Pepsinogen I reduction correlated with BMI percent decrease. CONCLUSIONS:
The exclusion of food transit is responsible for significant drop in gastric
output, hardly representing a risk factor in the remnant carcinogenesis, being
unexposed to alimentary carcinogenic agents.
PMID- 28508273
TI - Sleeve Gastrectomy: Correlation of Long-Term Results with Remnant Morphology and
Eating Disorders.
AB - BACKGROUND: Remnant dimension is considered one of the crucial elements
determining the success of sleeve gastrectomy (SG), and dilation of the gastric
fundus is often believed to be the main cause of failure. OBJECTIVES: The main
outcome of this study is to find correlations between remnant morphology in the
immediate post-operative stage, its dilation in years, and the long-term results.
The second purpose aims to correlate preoperative eating disorders, taste
alteration, hunger perception, and early satiety with post-SG results. MATERIALS
AND METHODS: Remnant morphology was evaluated, in the immediate post-operative
stage and over the years (>=2 years), through X-ray of the oesophagus-stomach
duodenum calculating the surface in anteroposterior (AP) and right anterior
oblique projection (RAO). Presurgery diagnosis of eating disorders and their
evaluation through "Eating Disorder Inventory-3" (EDI3) during follow-up were
performed. Change in taste perception, sense of appetite, and early satiety were
evaluated. Patients were divided into two groups: "failed SGs (EWL<50%) and
"efficient SGs" (EWL >50%). RESULTS: There were a total of 50 patients (37 F, 13
M), with mean age 52 years, preoperative weight 131 +/- 21.8 kg, and BMI 47.4 +/-
6.8 kg/m2. Post-operative remnant mean dimensions overlapped between the two
groups. On a long-term basis, an increase of 57.2 and 48.4% was documented in the
AP and RAO areas respectively. In "failed" SGs, dilation was significantly
superior to "efficient" SGs (AP area 70.2 vs 46.1%; RAO area 59.3 vs 39%; body
width 102% vs 41.7%). Preoperative eating disorders were more present in
efficient SGs than in failed SGs with the exception of sweet eating. There were
no significant changes to taste perception during follow-up. Fifty-two percent of
efficient SGs vs 26% of failed SGs reported a persistent lack of sense of hunger;
similarly, 92.5 vs 78% declared the persistence of a sense of early satiety. The
two groups did not statistically differ as far as all the variables of the EDI3
are concerned. CONCLUSION: On a long-term basis, the remnant mean dilation is
around 50% compared to the immediate post-operative stage but failed SGs showed
larger remnant dilation than efficient SGs and, in percentage, the more dilated
portion is the body of the stomach. As far as all the EDI3 variables obtained are
concerned, the two groups did not statistically differ. Of all eating disorders,
sweet eating seems to be weakly connected to SG failure.
PMID- 28508275
TI - Gross Olfaction Before and After Laparoscopic Gastric Bypass.
AB - BACKGROUND: Obesity leads to olfaction alterations, and this can further impact
food choices, appetite, and nutritional status. Bariatric procedures induce
weight loss and change in taste and smell perception, but more information is
needed, especially using objective olfaction tests. METHODS: A prospective study
was conducted during 6 months, with candidates to laparoscopic gastric bypass at
a single institution. A preoperative nasofibroscopy and gross smell
identification test (The Pocket Smell Test (r)) were performed in those meeting
the inclusion criteria. After 6 months, a new test was performed, and the primary
objective was to determine if there was an improvement in the olfaction score.
Weight loss and comorbidities improvement were also analyzed. RESULTS: From the
30 patients with morbid obesity enrolled, 21 met the inclusion criteria and ENT
evaluation. At baseline, 42.8% of patients scored 3 points, 53.3% scored 2
points, and 4.7% scored 1 point. After 6 months, there was a -81.1% of change.
Seventeen patients scored 3 points (p = 0.002 vs initial) and two scored 2 points
(p = 0.006 vs initial). There were no patients with less than 2 points. Weight
and comorbidities had a significant improvement as well. CONCLUSION: Laparoscopic
gastric bypass improves the olfaction scores of the Pocket Smell Test in morbidly
obese patients 6 months after their procedure. More complex tests can be used in
candidates to bariatric surgery if low scores are detected initially. Other
causes of olfaction dysfunctions should be determined if there is no improvement
after weight loss.
PMID- 28508276
TI - Effects of Sleeve Gastrectomy on Serum 12alpha-Hydroxylated Bile Acids in a
Diabetic Rat Model.
AB - BACKGROUND: Diabetes mellitus is a prevalent disease that endangers human health.
Bariatric surgery can effectively relieve insulin resistance with elevated serum
bile acids (BAs). 12alpha-Hydroxylated BAs were previously reported to be
associated with insulin resistance. The aim of this study was to analyze changes
in 12alpha-hydroxylated BA composition and possible associated mechanisms in
diabetic rats following sleeve gastrectomy (SG). METHODS: SG and sham operations
were performed in diabetic rats induced by high-fat diet feeding and
streptozotocin. Body weight, food intake, oral glucose tolerance test (OGTT),
insulin tolerance test (ITT), and serum BAs were analyzed at corresponding time
points. Cholesterol 12alpha-hydroxylase (CYP8B1) and transcription factor V-Maf
Avian Musculoaponeurotic Fibrosarcoma Oncogene Homolog G (MAFG) expression levels
were assessed by RT-PCR and western blotting. RESULTS: Compared with the SHAM
group, the SG group displayed significant weight loss from 6 weeks
postoperatively, accompanied by decreased food intake from 4 weeks after the
operation. At 2 and 12 weeks postoperatively, the areas under the curve of OGTT
and ITT were significantly decreased in the SG group. At 12 weeks post-operation,
the SG group displayed elevated serum BAs, but the percentage of 12alpha
hydroxylated BAs was reduced. Furthermore, SG rats exhibited higher MAFG and
lower CYP8B1 protein and mRNA levels in the liver (P < 0.05). CONCLUSION: The
percentage of 12alpha-hydroxylated bile acids was reduced after SG, which was
relevant with the inhibition of CYP8B1 and overexpression of MAFG. These outcomes
may play an important role in the improvement of insulin sensitivity following
SG.
PMID- 28508277
TI - Surgical Management of Obesity Among People with Schizophrenia and Bipolar
Disorder: a Systematic Review of Outcomes and Recommendations for Future
Research.
AB - BACKGROUND: People with schizophrenia or bipolar disorder (BD) exhibit very high
levels of obesity. Little is known about the potential benefits/risks of obesity
surgery. We conducted a narrative review to summarize the available knowledge on
bariatric surgery in people with schizophrenia or BD. METHODS: A systematic
search was conducted of major electronic databases from inception to October 2016
for studies investigating bariatric surgery among people with schizophrenia or
BD. Data were presented in a narrative synthesis and future research strategies
proposed. RESULTS: The electronic database searches identified 44 records. Eight
studies (BD, n = 265; schizophrenia: n = 14) were included with a mean study
length of 15.7 months (12-24). Seven found that bariatric surgery resulted in
weight loss in those with psychiatric disorders with an excess weight loss
ranging -31 to -70%. Six studies found that weight loss from bariatric surgery
was similar in people with schizophrenia or BD versus controls. However, most of
the studies limited their outcomes to only weight loss and did not measure
whether obesity surgery affected the status and treatment of psychiatric
symptoms. Although few adverse events were reported among patients with BD, data
from two studies demonstrated no significant deterioration of psychiatric
symptoms post-surgery in people with schizophrenia. CONCLUSIONS: Growing evidence
suggests that bariatric surgery may improve short-term weight status among people
with BD. However, given the paucity of studies for schizophrenia, and the lack of
information on medium-to long-term results, future large-scale high-quality
studies are required.
PMID- 28508279
TI - The coexistence of both replaced proper hepatic and gastroduodenal arteries due
to the common hepatic artery absence.
AB - Anatomical variants of the celiac trunk (CT) branches and especially these of
hepatic arteries (HAs) are among the most common variants of the arterial tree.
The knowledge of the wide variability in hepatic arterial supply is of paramount
importance in hepatobiliary, pancreatic, gastric, and esophageal surgery, as well
as in liver transplantations. The purpose of this case report is to describe a
rare variant discovered during abdominal dissection of a 74-year-old male cadaver
of Greek origin, in which the common hepatic artery was absent and its branches,
the proper hepatic artery (PHA) and the gastroduodenal artery (GDA) had an
aberrant and separate origin. The entire arterial supply to the liver derived
from the aberrant PHA, that originating from the superior mesenteric artery and
was named as PHA (RPHA). The RPHA, after a course posterior to the portal vein,
terminated into the right and left HAs, at the hilum. The GDA originated from the
CT, as well as the left gastric and splenic artery. The right gastric artery
originated from the PHA, as usual. The current case emphasizes the necessity of
preoperative imaging when evaluating the resectability of a tumor in
hepatobiliary and pancreatic area taking into account the possible vascular
variations. Abdominal surgeon should be aware of any aberrancy to avoid potential
iatrogenic injury and lethal complications.
PMID- 28508278
TI - Physiotherapy programme reduces fatigue in patients with advanced cancer
receiving palliative care: randomized controlled trial.
AB - PURPOSE: Cancer-related fatigue (CRF) is a common and relevant symptom in
patients with advanced cancer that significantly decreases their quality of life.
The aim of this study was to evaluate the effect of a physiotherapy programme on
CRF and other symptoms in patients diagnosed with advanced cancer. METHODS: The
study was designed as a randomized controlled trial. Sixty patients diagnosed
with advanced cancer receiving palliative care were randomized into two groups:
the treatment group (n = 30) and the control group (n = 30). The therapy took
place three times a week for 2 weeks. The 30-min physiotherapy session included
active exercises, myofascial release and proprioceptive neuromuscular
facilitation (PNF) techniques. The control group did not exercise. The outcomes
included Brief Fatigue Inventory (BFI), Edmonton Symptom Assessment Scale (ESAS)
and satisfaction scores. RESULTS: The exercise programme caused a significant
reduction in fatigue scores (BFI) in terms of severity of fatigue and its impact
on daily functioning. In the control group, no significant changes in the BFI
were observed. Moreover, the physiotherapy programme improved patients' general
well-being and reduced the intensity of coexisting symptoms such as pain,
drowsiness, lack of appetite and depression. The analysis of satisfaction scores
showed that it was also positively evaluated by patients. CONCLUSION: The
physiotherapy programme, which included active exercises, myofascial release and
PNF techniques, had beneficial effects on CRF and other symptoms in patients with
advanced cancer who received palliative care. The results of the study suggest
that physiotherapy is a safe and effective method of CRF management.
PMID- 28508280
TI - Treatment of spondylodiscitis after rectopexy: surgery is always required
Fauheron JL, Trilling B.
PMID- 28508281
TI - Perineal hernia repair after abdominoperineal excision or extralevator
abdominoperineal excision: a systematic review of the literature.
AB - BACKGROUND: The incidence of perineal hernia after abdominoperineal excision and
extralevator abdominoperineal excision ranges from 1 to 26%. In this systematic
review, we compared surgical options and postoperative outcomes of perineal
hernia repair in this setting from 2012 to 2016 with findings in a review of
publications 1944-2011. METHODS: We searched the PubMed database using the
keywords "hernia" AND "perineum" identified 392 papers published from 1946 to
2016. Two hundred and ninety-six papers published before 2012 were excluded and
96 were found to be potentially relevant. RESULTS: Twenty-one studies with a
total of 108 patients were included in the final analysis. Perineal hernia repair
was performed using the perineal approach in 75 patients (69.44%), the
laparoscopic approach in 25 patients (23.14%), the open abdominal approach in
three patients (2.77%) and the laparoscopic perineal approach in three patients
(2.77%) and the open abdominoperineal approach in two patients (1.8%). Non
absorbable mesh was used in 41 (37.96%) of cases, composite mesh in 20 (18.51%)
and biological mesh in 19 (17.59%). Flap reconstruction was used in 25 patients
(23.14%). First and second recurrences were observed in 26 (24.07%) and 7
(26.92%) cases, respectively. CONCLUSIONS: Comparison of perineal hernia repair
from 1944 to 2011 and from 2012 to 2016 showed that perineal and laparoscopic
approaches are currently the most commonly used techniques. Primary defect
closure was abandoned in favor of synthetic or composite mesh placement. Use of
flap reconstruction spread rapidly and the recurrence rate was low. Randomized
control trials and a larger sample size are needed to confirm these data and to
develop a gold standard treatment for secondary hernia repair after
abdominoperineal excision or extralevator abdominoperineal excision.
PMID- 28508283
TI - Young adults self-derive and retain new factual knowledge through memory
integration.
AB - The present research investigated the retention of new factual knowledge derived
through integration of information acquired across temporally distributed
learning episodes. Young adults were exposed to novel facts as they read long
lists of seemingly unrelated information, one sentence at a time. They then were
presented open-ended questions, the answers to which could be self-derived
through integration of pairs of facts from the list. Experiment 1 was the first
test of self-derivation of new factual knowledge through integration in adults
using open-ended testing (as opposed to forced-choice testing). Participants
successfully self-derived integrated knowledge under these more challenging
conditions. Experiment 2 was a test for long-term retention of newly self-derived
information. Newly derived knowledge remained accessible after a 1-week delay.
Striking individual differences were also observed, which were related to whether
individuals spontaneously identified the relational structure of the learning
task. Insight into the relation between explicit task knowledge and strategic
processing was also revealed through examination of response speed at the time of
test. Specifically, knowledge of the task structure was associated with response
latencies on unsuccessful (but not successful) trials, such that participants who
were aware of the opportunity to integrate spent longer when they were
subsequently unsuccessful, presumably reflecting directed search strategies and
heightened perseverance when those processes failed. Together, the present
findings provide direct evidence for the role of memory integration in the long
term accumulation of a semantic knowledge base and have theoretical implications
for our understanding of this fundamental form of learning.
PMID- 28508282
TI - Malignancy Incidence, Management, and Prevention in Patients with Rheumatoid
Arthritis.
AB - Traditional and biologic disease-modifying antirheumatic drugs (DMARDs) are
effective medications for the management of rheumatoid arthritis (RA). However,
the effects of these medications on immune function raises concern that they may
increase long-term cancer risk. The baseline risk for some cancers appears to
differ in patients with RA compared to the general population, with the former
having an increased risk of lymphoma, lung cancer and renal cancer, but a
decreased risk of colorectal and breast cancer. Some DMARDs appear to increase
the rate of specific cancer types (such as bladder cancer with cyclophosphamide),
but few appear to increase the overall cancer risk. Studying the link between
lymphoma and disease severity in RA is complicated because patients with
persistently active disease are at increased risk for lymphoma, and disease
severity correlates with more intense use of immunosuppressive medications.
Overall, cancer risk in patients with RA is slightly above that of the general
population, with the increased risk likely secondary to an increased risk of
lymphomas in those with high disease activity. Risk mitigation includes
management of RA disease activity as well as age- and sex-appropriate cancer
screening.
PMID- 28508285
TI - Flame Atmospheric Pressure Chemical Ionization Coupled with Negative Electrospray
Ionization Mass Spectrometry for Ion Molecule Reactions.
AB - Flame atmospheric pressure chemical ionization (FAPCI) combined with negative
electrospray ionization (ESI) mass spectrometry was developed to detect the
ion/molecule reactions (IMRs) products between nitric acid (HNO3) and negatively
charged amino acid, angiotensin I (AI) and angiotensin II (AII), and insulin
ions. Nitrate and HNO3-nitrate ions were detected in the oxyacetylene flame,
suggesting that a large quantity of nitric acid (HNO3) was produced in the flame.
The HNO3 and negatively charged analyte ions produced by a negative ESI source
were delivered into each arm of a Y-shaped stainless steel tube where they merged
and reacted. The products were subsequently characterized with an ion trap mass
analyzer attached to the exit of the Y-tube. HNO3 showed the strongest affinity
to histidine and formed (Mhistidine-H+HNO3)- complex ions, whereas some amino
acids did not react with HNO3 at all. Reactions between HNO3 and histidine
residues in AI and AII resulted in the formation of dominant [MAI-H+(HNO3)]- and
[MAII-H+(HNO3)]- ions. Results from analyses of AAs and insulin indicated that
HNO3 could not only react with basic amino acid residues, but also with disulfide
bonds to form [M-3H+(HNO3)n]3- complex ions. This approach is useful for
obtaining information about the number of basic amino acid residues and disulfide
bonds in peptides and proteins. Graphical Abstract ?.
PMID- 28508284
TI - Repeatability of quantitative parameters of 18F-fluoride PET/CT and biochemical
tumour and specific bone remodelling markers in prostate cancer bone metastases.
AB - PURPOSE: 18F-fluoride PET/CT exhibits high sensitivity to delineate and measure
the extent of bone metastatic disease in patients with prostate cancer. 18F
fluoride PET/CT could potentially replace traditional bone scintigraphy in
clinical routine and trials. However, more studies are needed to assess
repeatability and biological uptake variation. The aim of this study was to
perform test-retest analysis of quantitative PET-derived parameters and
blood/serum bone turnover markers at the same time point. Ten patients with
prostate cancer and verified bone metastases were prospectively included. All
underwent two serial 18F-fluoride PET/CT at 1 h post-injection. Up to five
dominant index lesions and whole-body 18F-fluoride skeletal tumour burden were
recorded per patient. Lesion-based PET parameters were SUVmax, SUVmean and
functional tumour volume applying a VOI with 50% threshold (FTV50%). The total
skeletal tumour burden, total lesion 18F-fluoride (TLF), was calculated using a
threshold of SUV of >=15. Blood/serum biochemical bone turnover markers obtained
at the time of each PET were PSA, ALP, S-osteocalcin, S-beta-CTx, 1CTP and BAP.
RESULTS: A total of 47 index lesions and a range of 2-122 bone metastases per
patient were evaluated. Median time between 18F-fluoride PET/CT was 7 days (range
6-8 days). Repeatability coefficients were for SUVmax 26%, SUVmean 24%, FTV50%
for index lesions 23% and total skeletal tumour burden (TLF) 35%. Biochemical
bone marker repeatability coefficients were for PSA 19%, ALP 23%, S-osteocalcin
18%, S-beta-CTx 22%, 1CTP 18% and BAP 23%. CONCLUSIONS: Quantitative 18F-fluoride
uptake and simultaneous biochemical bone markers measurements are reproducible
for prostate cancer metastases and show similar magnitude in test-retest
variation.
PMID- 28508286
TI - Sample Preparation of Corn Seed Tissue to Prevent Analyte Relocations for Mass
Spectrometry Imaging.
AB - Corn seed tissue sections were prepared by the tape support method using an
adhesive tape, and mass spectrometry imaging (MSI) was performed. The effect of
heat generated during sample preparation was investigated by time-of-flight
secondary mass spectrometry (TOF-SIMS) imaging of corn seed tissue prepared by
the tape support and the thaw-mounted methods. Unlike thaw-mounted sample
preparation, the tape support method does not cause imaging distortion because of
the absence of heat, which can cause migration of the analytes on the sample. By
applying the tape-support method, the corn seed tissue was prepared without
structural damage and MSI with accurate spatial information of analytes was
successfully performed. Graphical Abstract ?.
PMID- 28508287
TI - [Pathology of familial tumor syndromes].
PMID- 28508288
TI - Repetitive postoperative extubation failure and cardiac arrest due to
laryngomalacia after general anesthesia in an elderly patient: a case report.
AB - The authors report a case involving an elderly patient who experienced repetitive
perioperative cardiac arrest caused by laryngomalacia. The patient underwent
surgery under general anesthesia; however, 2 h after initial extubation, he
experienced cardiopulmonary arrest. Return of spontaneous circulation was
achieved by immediate resuscitation. Four hours later, a second extubation was
performed without any neurological complications. However, 2 h later, he
experienced cardiopulmonary arrest again. Immediately after the third extubation,
12 h after the second cardiopulmonary arrest, fiberoptic laryngoscopy revealed
laryngomalacia. His respiratory condition stabilized after emergent tracheostomy.
Laryngomalacia should be considered even in adult cases when signs of upper
airway obstruction manifest after extubation.
PMID- 28508289
TI - Somatic mosaicism with reversion to normality of a mutated transthyretin allele
related to a familial amyloidotic polyneuropathy.
AB - Familial amyloidotic polyneuropathy (FAP) is a progressive neuropathy, with onset
in adulthood and high mortality. It is related to an altered transthyretin (TTR)
plasma protein, mainly produced by the liver and responsible for amyloid deposit
in the peripheral nervous system. SNPs in the TTR gene were associated with FAP,
and the G>C substitution (NM_000371.3:c.325G>C) in the 109th codon (GAG vs CAG;
NP_362.1:p.E109Q) was previously described in Sicily (Italy). Here, we report on
a Sicilian family with several patients affected by FAP related to the E109Q
mutation, which displayed a somatic mosaicism with the reversion to normality of
the c.325G>C mutation. After exclusion of isodisomy and allele deletion, this
event seems to be due to a rare, post-zygotic interallelic gene conversion with
the wild-type allele serving as a donor. Further investigations will be necessary
to better understand the molecular basis of this phenomenon, and could help
determine if this can be induced in a targeted manner in the context of natural
gene therapy to treat TTR-related FAP patients, as previously proposed for other
diseases. Moreover, our results confirm the need to perform DNA-based diagnostic
tests with at least a second tissue when a suspected germline mutation in a
candidate gene is not identified in the first tissue.
PMID- 28508292
TI - Prof. Dr. Kurt Jellinger: an appreciation.
PMID- 28508290
TI - CRISPR/Cas9-mediated somatic and germline gene correction to restore hemostasis
in hemophilia B mice.
AB - Hemophilia B (HB) is an X-linked disorder caused by defects of F9 encoded
coagulation factor IX, which is an ideal model for gene therapy. Most existing HB
gene therapies are based on viral mediated gene supplementation, which could
increase immunoreaction. In this study, CRISPR/Cas9 system was used for gene
correction in an F9 mutant HB mouse model in both adult mice (in vivo) and in
germline cells (ex vivo). In vivo, naked Cas9-sgRNA plasmid and donor DNA were
delivered to HB mice livers to recover the mutation via hydrodynamic tail vein
(HTV) injection. 62.5% of the HTV-treated mice showed a detectable gene
correction (>1%) in the F9 alleles of hepatocytes, which was sufficient to remit
the coagulation deficiency. Ex vivo, three different forms of Cas9 were
microinjected into germline cells of HB mice to investigate their efficiency and
safety in gene correction. Cas9 protein showed higher gene recovery rates, less
embryo toxicity, and lower mosaic repair percentage, making it more suitable for
germline gene therapy. Our study strongly supports that CRISPR/Cas9-mediated
genome editing is feasible in gene therapy of genetic disorders.
PMID- 28508291
TI - Lobular homology in cerebellar hemispheres of humans, non-human primates and
rodents: a structural, axonal tracing and molecular expression analysis.
AB - Comparative neuroanatomy provides insights into the evolutionary functional
adaptation of specific mammalian cerebellar lobules, in which the lobulation
pattern and functional localization are conserved. However, accurate
identification of homologous lobules among mammalian species is challenging. In
this review, we discuss the inter-species homology of crus I and II lobules which
occupy a large volume in the posterior cerebellar hemisphere, particularly in
humans. Both crus I/II in humans are homologous to crus I/II in non-human
primates, according to Paxinos and colleagues; however, this area has been
defined as crus I alone in non-human primates, according to Larsell and Brodal.
Our neuroanatomical analyses in humans, macaques, marmosets, rats, and mice
demonstrate that both crus I/II in humans are homologous to crus I/II or crus I
alone in non-human primates, depending on previous definitions, and to crus I
alone in rodents. Here, we refer to the region homologous to human crus I/II
lobules as "ansiform area (AA)" across animals. Our results show that the AA's
olivocerebellar climbing fiber and Purkinje cell projections as well as aldolase
C gene expression patterns are both distinct and conserved in marmosets and
rodents. The relative size of the AA, as represented by the AA volume fraction in
the whole cerebellum was 0.34 in human, 0.19 in macaque, and approximately 0.1 in
marmoset and rodents. These results indicate that the AA reflects an
evolutionarily conserved structure in the mammalian cerebellum, which is
characterized by distinct connectivity from neighboring lobules and a massive
expansion in skillful primates.
PMID- 28508294
TI - Preoperative MRI is helpful but not sufficient to detect associated lesions in
patients with chronic ankle instability.
AB - PURPOSE: The aim of this study was to determine the reliability and validity of
preoperative magnetic resonance imaging (MRI) scans for the detection of
additional pathologies in patients with chronic ankle instability (CAI) compared
to arthroscopic findings. METHODS: Preoperative MRI images of 30 patients were
evaluated regarding articular and periarticular comorbidities and compared to
intraoperative findings. The reliability of MRI was determined by calculating
specificity, sensitivity, as well as positive and negative predictive values. The
accuracy of the classification of cartilage lesions by Outerbridge and Berndt and
Harty rating scales was determined by calculating the area under the receiver
operating curve (AUC). RESULTS: In total, 72 additional pathologies were found
arthroscopically compared to 73 lesions gathered from MRI images. Sensitivity
ranged from 89% for peroneal tendinopathy to 28% for additional ligamentous
lesions. Specificity ranged from 100% for anterolateral impingement, loose bodies
and peroneal tendinopathy to 38% for additional ligamentous lesions. For
cartilage lesions, sensitivity was at 91% and specificity was at 55% for the
Outerbridge grading scale. For the Berndt and Harty classification system,
sensitivity was at 91% and specificity was at 28%. Correlation of additional
pathologies ranged from weak (r s = 0.48; p = 0.02) to moderate results (r s =
0.67; p < 0.001). CONCLUSION: CAI is associated with a high incidence of
additional pathologies. In some cases, MRI delivers insufficient results, which
may lead to misinterpretation of present comorbidities. MRI is a helpful tool for
preoperative evaluation, but arthroscopy remains gold standard in the diagnosis
of associated lesions in patients with CAI. LEVEL OF EVIDENCE: III.
PMID- 28508295
TI - MRI-based tendon bone healing is related to the clinical functional scores at the
first year after anterior cruciate ligament reconstruction with hamstring tendon
autograft.
AB - PURPOSE: The correlation between tendon bone healing and clinical functional
scores after anterior cruciate ligament reconstruction (ACLR) using four-stranded
hamstring tendon autograft has rarely being reported. The purpose of this study
was to determine the correlation between magnetic resonance imaging (MRI)-based
tendon bone healing and clinical functional scores after ACLR using hamstring
tendon. METHODS: Thirty-eight patients with ACLR using four-stranded hamstring
tendon autograft were included in this prospective study in the authors' hospital
from 2013 to 2014. All patients were performed Tegner, Lysholm, International
Knee Documentation Committee (IKDC) subjective scores, KT-1000 and MRI
examinations in 3, 6, 12 months after the operation, respectively. According to
MRI, the healing degree of tendon bone was divided into five grades, and the
healing degree of the tendon at different time points was evaluated. Moreover,
the correlations between the clinical scores and tendon bone healing level at 12
months after the operation were determined. RESULTS: The Tegner, Lysholm, and
IKDC scores of all patients were gradually improved over time after ACLR, and the
degree of tendon bone healing was gradually increased. Moreover, there were
significantly positive correlations between the level of tendon bone healing and
the clinical functional scores at 12 months after the operation. CONCLUSION: The
clinical functional scores and the degree of tendon bone healing were gradually
improved over time after ACLR. Moreover, there were significant positive
correlations between the level of tendon bone healing and clinical functional
scores of knee joint at the first year after the operation. LEVEL OF EVIDENCE:
III.
PMID- 28508293
TI - Influenza infection and heart failure-vaccination may change heart failure
prognosis?
AB - The interaction of influenza infection with the pathogenesis of acute heart
failure (AHF) and the worsening of chronic heart failure (CHF) is rather complex.
The deleterious effects of influenza infection on AHF/CHF can be attenuated by
specific immunization. Our review aimed to summarize the efficacy, effectiveness,
safety, and dosage of anti-influenza vaccination in HF. In this literature
review, we searched MEDLINE and EMBASE from January 1st 1966 to December 31st,
2016, for studies examining the association between AHF/CHF, influenza
infections, and anti-influenza immunizations. We used broad criteria to increase
the sensitivity of the search. HF was a prerequisite for our search. The search
fields used included "heart failure," "vaccination," "influenza," "immunization"
along with variants of these terms. No restrictions on the type of study design
were applied. The most common clinical scenario is exacerbation of pre-existing
CHF by influenza infection. Scarce evidence supports a potential positive
association of influenza infection with AHF. Vaccinated patients with pre
existing CHF have reduced all-cause morbidity and mortality, but effects are not
consistently documented. Immunization with higher antigen quantity may confer
additional protection, but such aggressive approach has not been generally
advocated. Further studies are needed to delineate the role of influenza
infection on AHF/CHF pathogenesis and maintenance. Annual anti-influenza
vaccination appears to be an effective measure for secondary prevention in HF.
Better immunization strategies and more efficacious vaccines are urgently
necessary.
PMID- 28508296
TI - Modeling the Fear Effect in Predator-Prey Interactions with Adaptive Avoidance of
Predators.
AB - Recent field experiments on vertebrates showed that the mere presence of a
predator would cause a dramatic change of prey demography. Fear of predators
increases the survival probability of prey, but leads to a cost of prey
reproduction. Based on the experimental findings, we propose a predator-prey
model with the cost of fear and adaptive avoidance of predators. Mathematical
analyses show that the fear effect can interplay with maturation delay between
juvenile prey and adult prey in determining the long-term population dynamics. A
positive equilibrium may lose stability with an intermediate value of delay and
regain stability if the delay is large. Numerical simulations show that both
strong adaptation of adult prey and the large cost of fear have destabilizing
effect while large population of predators has a stabilizing effect on the
predator-prey interactions. Numerical simulations also imply that adult prey
demonstrates stronger anti-predator behaviors if the population of predators is
larger and shows weaker anti-predator behaviors if the cost of fear is larger.
PMID- 28508297
TI - Adaptation to Stochastic Temporal Variations in Intratumoral Blood Flow: The
Warburg Effect as a Bet Hedging Strategy.
AB - While most cancers promote ingrowth of host blood vessels, the resulting vascular
network usually fails to develop a mature organization, resulting in abnormal
vascular dynamics with stochastic variations that include slowing, cessation, and
even reversal of flow. Thus, substantial spatial and temporal variations in
oxygen concentration are commonly observed in most cancers. Cancer cells, like
all living systems, are subject to Darwinian dynamics such that their survival
and proliferation are dependent on developing optimal phenotypic adaptations to
local environmental conditions. Here, we consider the environmental stresses
placed on tumors subject to profound, frequent, but stochastic variations in
oxygen concentration as a result of temporal variations in blood flow. While
vascular fluctuations will undoubtedly affect local concentrations of a wide
range of molecules including growth factors (e.g., estrogen), substrate (oxygen,
glucose, etc.), and metabolites ([Formula: see text], we focus on the selection
forces that result solely from stochastic fluctuations in oxygen concentration.
The glucose metabolism of cancer cells has been investigated for decades
following observations that malignant cells ferment glucose regardless of oxygen
concentration, a condition termed the Warburg effect. In contrast, normal cells
cease fermentation under aerobic conditions and this physiological response is
termed the Pasteur effect. Fermentation is markedly inefficient compared to
cellular respiration in terms of adenosine triphosphate (ATP) production,
generating just 2 ATP/glucose, whereas respiration generates 38 ATP/glucose. This
inefficiency requires cancer cells to increase glycolytic flux, which
subsequently increases acid production and can significantly acidify local
tissue. Hence, it initially appears that cancer cells adopt a disadvantageous
metabolic phenotype. Indeed, this metabolic "hallmark" of cancer is termed
"energy dysregulation." However, if cancers arise through an evolutionary
optimization process, any common observed property must confer an adaptive
advantage. In the present work, we investigate the hypothesis that aerobic
glycolysis represents an adaptation to stochastic variations in oxygen
concentration stemming from disordered intratumoral blood flow. Using
mathematical models, we demonstrate that the Warburg effect evolves as a
conservative metabolic bet hedging strategy in response to stochastic
fluctuations of oxygen. Specifically, the Warburg effect sacrifices fitness in
physoxia by diverting resources from the more efficient process of respiration,
but preemptively adapts cells to hypoxia because fermentation produces ATP
anaerobically. An environment with sufficiently stochastic fluctuations of oxygen
will select for the bet hedging (Warburg) phenotype since it is modestly
successful irrespective of oxygen concentration.
PMID- 28508298
TI - Stability of Control Networks in Autonomous Homeostatic Regulation of Stem Cell
Lineages.
AB - Design principles of biological networks have been studied extensively in the
context of protein-protein interaction networks, metabolic networks, and
regulatory (transcriptional) networks. Here we consider regulation networks that
occur on larger scales, namely the cell-to-cell signaling networks that connect
groups of cells in multicellular organisms. These are the feedback loops that
orchestrate the complex dynamics of cell fate decisions and are necessary for the
maintenance of homeostasis in stem cell lineages. We focus on "minimal" networks
that are those that have the smallest possible numbers of controls. For such
minimal networks, the number of controls must be equal to the number of
compartments, and the reducibility/irreducibility of the network (whether or not
it can be split into smaller independent sub-networks) is defined by a matrix
comprised of the cell number increments induced by each of the controlled
processes in each of the compartments. Using the formalism of digraphs, we show
that in two-compartment lineages, reducible systems must contain two 1-cycles,
and irreducible systems one 1-cycle and one 2-cycle; stability follows from the
signs of the controls and does not require magnitude restrictions. In three
compartment systems, irreducible digraphs have a tree structure or have one 3
cycle and at least two more shorter cycles, at least one of which is a 1-cycle.
With further work and proper biological validation, our results may serve as a
first step toward an understanding of ways in which these networks become
dysregulated in cancer.
PMID- 28508299
TI - Intensity response function of the photopic negative response (PhNR): effect of
age and test-retest reliability.
AB - PURPOSE: To assess the effect of age and test-retest reliability of the intensity
response function of the full-field photopic negative response (PhNR) in normal
healthy human subjects. METHODS: Full-field electroretinograms (ERGs) were
recorded from one eye of 45 subjects, and 39 of these subjects were tested on two
separate days with a Diagnosys Espion System (Lowell, MA, USA). The visual
stimuli consisted of brief (<5 ms) red flashes ranging from 0.00625 to 6.4 phot
cd.s/m2, delivered on a constant 7 cd/m2 blue background. PhNR amplitudes were
measured at its trough from baseline (BT) and from the preceding b-wave peak
(PT), and b-wave amplitude was measured at its peak from the preceding a-wave
trough or baseline if the a-wave was not present. The intensity response data of
all three ERG measures were fitted with a generalized Naka-Rushton function to
derive the saturated amplitude (V max), semisaturation constant (K) and slope (n)
parameters. Effect of age on the fit parameters was assessed with linear
regression, and test-retest reliability was assessed with the Wilcoxon signed
rank test and Bland-Altman analysis. Holm's correction was applied to account for
multiple comparisons. RESULTS: V max of BT was significantly smaller than that of
PT and b-wave, and the V max of PT and b-wave was not significantly different
from each other. The slope parameter n was smallest for BT and the largest for b
wave and the difference between the slopes of all three measures were
statistically significant. Small differences observed in the mean values of K for
the different measures did not reach statistical significance. The Wilcoxon
signed-rank test indicated no significant differences between the two test visits
for any of the Naka-Rushton parameters for the three ERG measures, and the Bland
Altman plots indicated that the mean difference between test and retest
measurements of the different fit parameters was close to zero and within 6% of
the average of the test and retest values of the respective parameters for all
three ERG measurements, indicating minimal bias. While the coefficient of
reliability (COR, defined as 1.96 times the standard deviation of the test and
retest difference) of each fit parameter was more or less comparable across the
three ERG measurements, the %COR (COR normalized to the mean test and retest
measures) was generally larger for BT compared to both PT and b-wave for each fit
parameter. The Naka-Rushton fit parameters did not show statistically significant
changes with age for any of the ERG measures when corrections were applied for
multiple comparisons. However, the V max of BT demonstrated a weak correlation
with age prior to correction for multiple comparisons, and the effect of age on
this parameter showed greater significance when the measure was expressed as a
ratio of the V max of b-wave from the same subject. CONCLUSION: V max of the BT
amplitude measure of PhNR at the best was weakly correlated with age. None of the
other parameters of the Naka-Rushton fit to the intensity response data of either
the PhNR or the b-wave showed any systematic changes with age. The test-retest
reliability of the fit parameters for PhNR BT amplitude measurements appears to
be lower than those of the PhNR PT and b-wave amplitude measurements.
PMID- 28508300
TI - The Symbolic Nature of Trust in Heterosexual Adolescent Romantic Relationships.
AB - Trust contributes to young people's capacity for sustaining current and future
successful relationships. To date, research has yet to examine the meaning of
trust in early dating relationships and reasons for its deterioration. The
present study focused on video-recorded conversations about trust between 34
heterosexual adolescent couples in dating relationships living in the U.S.
Transcripts from these conversations were qualitatively analyzed using thematic
analysis to identify adolescents' meanings of trust and reasons they provided for
a lack of trust in their romantic partners. All 34 couples identified concerns
specifically related to infidelity. Six major themes for not trusting romantic
partners emerged. Results suggested that the lack of trust in romantic
relationships might stem from several areas that are directly and indirectly
related to the current relationship, including low self-esteem, the experience of
betrayal in past romantic relationships, partners' extradyadic behaviors, and
gossip among peers. Importantly, peers can play a defining role in influencing
young people's perceptions of their romantic partners and developing or
sustaining trust in their romantic relationships.
PMID- 28508301
TI - Sublingual heterotopic large cyst in a newborn: anesthetic management.
PMID- 28508302
TI - Handedness and Attention Deficit/Hyperactivity Disorder Symptoms in College
Students.
AB - The symptoms of adult Attention Deficit/Hyperactivity Disorder (ADHD) generally
include impaired concentration; an insensitivity to social cues, being hard to
get along with, and being internally restlessness. It is not surprising that
these problems are likely to affect the performance of college students with
ADHD. The study aims to examine whether ADHD symptoms are associated with
handedness in college students in Taiwan. A total of 505 male and 645 female
participants completed Annett's handedness questionnaire and the Traditional
Chinese College ADHD Response Evaluation Student Response Inventory (C-CARE-SRI).
Handedness was scored both categorically, mixed vs. not-mixed, and continuously,
using the Hand Preference Index. The Inattention score was significantly higher
for students who were mixed-handed than for those who were not, after social
pressure against using the left hand to write had been adjusted for. However, the
differences in Hyperactivity and Impulsivity scores were nonsignificant. In
addition, the correlations between all three ADHD and Hand Preference Index
factor-scores were nonsignificant. To sum up, mixed-handedness is associated with
a higher Inattention score. The potential underlying mechanism relating to ADHD
Inattention is discussed.
PMID- 28508303
TI - The effect of anger expression style on cardiovascular responses to lateralized
cognitive stressors.
AB - To determine the effects of self-reported anger expression style on cerebrally
lateralized physiological responses to neuropsychological stressors, changes in
systolic blood pressure and heart rate were examined in response to a verbal
fluency task and a figural fluency task among individuals reporting either "anger
in" or "anger out" expression styles. Significant group by trial interaction
effects was found for systolic blood pressure following administration of verbal
fluency [F(1,54) = 5.86, p < 0.05] and nonverbal fluency stressors [F(1,54) =
13.68, p < .001]. Similar interactions were seen for systolic heart rate
following administration of verbal fluency [F(1,54) = 5.86, p < .005] and
nonverbal fluency stressors [F(1,54) = 13.68, p < .001]. The corresponding
results are discussed in terms of functional cerebral systems and potential
implications for physiological models of anger. Given the association between
anger and negative physical health outcomes, there is a clear need to better
understand the physiological components of anger. The results of this experiment
indicate that a repressive "anger in" expression style is associated with
deregulation of the right frontal region. This same region has been shown to be
intimately involved in cardiovascular recovery, glucose metabolism, and blood
pressure regulation.
PMID- 28508304
TI - Effects of Pesticide Mixtures on Zooplankton Assemblages in Aquatic Microcosms
Simulating Rice Paddy Fields.
AB - The individual and combined effects of pesticides (chlorpyrifos, triadimefon and
butachlor) on the zooplankton assemblages of microcosms were investigated.
Laboratory microcosms were constructed with water and sediment to simulate
aquatic conditions in China's rice paddy fields. Results from principal response
curves analysis showed that butachlor and triadimefon had no significant impact
individually on the population level in zooplankton assemblages. The deleterious
effects of pesticide mixtures on the zooplankton were mainly caused by
chlorpyrifos. In fact, assemblage succession only occurred in the treatments
containing chlorpyrifos. There was no synergy effect on the microcosm from
combinations of pesticides on the assemblages. The zooplankton assemblages
affected by chlorpyrifos did not recover at the termination of the experiment,
i.e., after 56 days.
PMID- 28508306
TI - Multicenter, Randomized, Investigator-Masked Study Comparing Brimonidine Tartrate
0.1% and Timolol Maleate 0.5% as Adjunctive Therapies to Prostaglandin Analogues
in Normal-Tension Glaucoma.
AB - INTRODUCTION: This study compared the efficacy and safety of adjunctive
brimonidine tartrate 0.1% ophthalmic solution (brimonidine) and timolol maleate
0.5% ophthalmic solution (timolol) in prostaglandin analogue (PGA)-treated normal
tension glaucoma (NTG), assessing the non-inferiority of brimonidine in terms of
intraocular pressure (IOP) reduction. METHODS: In this multicenter, randomized,
investigator-masked, parallel-group, clinical study, adjunctive brimonidine or
timolol was administered twice daily for 12 weeks in eyes with NTG that had been
treated with PGA for at least 90 days and required additional treatment despite
an IOP of 16 mmHg or less. IOP was measured on at least three visits before add
on therapy (mean baseline IOP), and at weeks 4, 8, and 12 after adjunctive
administration. Systolic/diastolic blood pressure, pulse rate, and adverse events
(AEs) were recorded at each visit. RESULTS: A total of 152 individuals were
enrolled and 128 (84.2%) were eligible for efficacy analyses. IOP in both groups
at each visit decreased significantly from baseline (P < 0.001). However, the
difference in the change from baseline IOP at week 12 between the brimonidine (
1.05 +/- 1.81 mmHg) and timolol (-1.41 +/- 1.40 mmHg) groups was 0.36 mmHg (95%
confidence interval [CI] [-0.21, 0.92]), which exceeded the value of the non
inferiority margin (0.75 mmHg). Baseline systolic/diastolic blood pressure
decreased significantly in both groups at certain visits (P < 0.05), while
baseline pulse rates decreased significantly in the timolol group (P < 0.001),
with no significant differences in the brimonidine group. AE-related treatment
discontinuation occurred in 2/71 (2.8%) and 2/75 (2.7%) patients in the
brimonidine and timolol groups, respectively. CONCLUSION: This study demonstrated
an add-on effect of brimonidine to PGAs, although non-inferiority of brimonidine
to timolol as adjunctive therapy in PGA-treated NTG in terms of IOP reduction was
not observed. Brimonidine was associated with no adverse effects on pulse rate.
FUNDING: Senju Pharmaceutical Co., Ltd. TRIAL REGISTRATION: UMIN Clinical Trials
Registry identifier, UMIN000014810.
PMID- 28508305
TI - Recent advances in targeting DNA repair pathways for the treatment of ovarian
cancer and their clinical relevance.
AB - Poly (ADP-ribose) polymerase (PARP) inhibitors have attracted much attention as
one of the major molecular-targeted therapeutics for inhibiting DNA damage
response. The PARP inhibitor, olaparib, has been clinically applied for treating
certain recurrent ovarian cancer patients with BRCA1/2 mutations in Europe and
the United States. It was also designated on 24 March 2017 as an orphan drug in
Japan for similar clinical indications. In this review, we discuss (i) the
prevalence of BRCA1/2 mutations in ovarian cancer, (ii) clinical trials of PARP
inhibitors in ovarian cancer, (iii) genetic counseling for hereditary breast and
ovarian cancer patients, and (iv) non-BRCA genes that may be associated with
homologous recombination deficiency.
PMID- 28508307
TI - Duration of Antiviral Prophylaxis and Risk of Herpes Zoster among Patients
Receiving Autologous Hematopoietic Stem Cell Transplants: A Retrospective,
Observational Study.
AB - INTRODUCTION: There are no real-world data on antiviral prophylaxis (AP) duration
and risk of herpes zoster (HZ) given AP duration in patients receiving autologous
hematopoietic stem cell transplants (auto-HSCT). The objectives of this study are
to describe the duration of AP and to compare incidence of HZ by AP duration in
auto-HSCT patients. METHODS: This is a retrospective, observational database
(Marketscan(r)) study. This study included patients >=18 years old who had auto
HSCT during 2009-2013, had chemotherapy within 60 days prior to auto-HSCT (latest
chemotherapy date within the 60 days was the study enrollment date), and had
continuous health plan enrollment for at least 365 days before and after the
study enrollment date. AP duration was the sum of days supply of all AP
prescriptions from 30 days before to 365 days after the study enrollment date.
Patients were followed from the study enrollment date to the end of continuous
health plan enrollment, death, or December 31, 2014 to assess HZ incidence. The
Cox proportional hazards model was used to examine the association between the
risk of HZ and AP duration. RESULTS: This study identified 1959 eligible auto
HSCT patients, of whom 93.0% were prescribed AP. Average AP duration was 220 days
(SD = 122), while 200 (11%) patients had AP for >=1 year. HZ incidence was
42.4/1000 person-years (PY) (95% CI 36.5, 49.0) for the overall auto-HSCT cohort.
Among patients who received AP, duration of AP prescriptions and HZ incidence
were inversely related. Compared with patients who were on AP for 1-89 days,
patients with AP duration of 180-269 days [hazard ratio (HR) = 0.576, p = 0.019],
270-359 days (HR = 0.594, p = 0.023), and >=360 days (HR = 0.309, p < 0.001) had
significantly lower risk of HZ. CONCLUSION: Auto-HSCT patients are at increased
risk for HZ, even when prescribed AP. A safe and effective vaccine against HZ for
auto-HSCT patients could be a useful adjunctive prevention strategy.
PMID- 28508308
TI - TRP Channel Classification.
AB - The transient receptor potential (TRP) ion channels are named after the discovery
of the photo-transducted channels in Drosophila. TRPs, activated by various
extracellular and intracellular stimuli, play a plethora of physiological and
pathological roles. There are seven families of TRPs including TRPC (canonical),
TRPV (vanilloid), TRPM (melastatin), TRPA (ankyrin), TRPP (polycystin), TRPML
(mucolipin), and TRPN (Drosophila NOMPC) in mammals. In yeast, the eighth TRP
family was recently identified and named as TRPY. We here briefly summarize the
classification and function of TRP cation channel superfamily.
PMID- 28508309
TI - TRPC Channel Structure and Properties.
AB - TRPC channels are the first identified members in the TRP family. They function
as either homo- or heterotetramers regulating intracellular Ca2+ concentration in
response to numerous physiological or pathological stimuli. TRPC channels are
nonselective cation channels permeable to Ca2+. The properties and the functional
domains of TRPC channels have been identified by electrophysiological and
biochemical methods. However, due to the large size, instability, and flexibility
of their complexes, the structures of the members in TRPC family remain
unrevealed. More efforts should be made on structure analysis and generating good
tools, including specific antibodies, agonist, and antagonist.
PMID- 28508310
TI - TRPC Channel Downstream Signaling Cascades.
AB - The family of TRP channel is comprised of a large group of cation-permeable
channels, displaying as signaling integrators for sensing extracellular stimulus
and initiating intracellular signaling cascades. This chapter offers a brief
review of the signaling molecules related to TRPC channels, the first identified
mammalian TRP family. Besides the signaling molecules involved in TRPC
activation, I will focus on their upstream and downstream signaling cascades and
the molecules involved in their intracellular trafficking.
PMID- 28508311
TI - TRPC Channels in Health and Disease.
AB - This chapter offers a brief introduction of the functions of TRPC channels in non
neuronal systems. We focus on three major organs of which the research on TRPC
channels have been most focused on: kidney, heart, and lung. The chapter
highlights on cellular functions and signaling pathways mediated by TRPC
channels. It also summarizes several inherited diseases in humans that are
related to or caused by TRPC channel mutations and malfunction. A better
understanding of TRPC channels functions and the importance of TRPC channels in
health and disease should lead to new insights and discovery of new therapeutic
approaches for intractable disease.
PMID- 28508312
TI - TRPC Channels and Programmed Cell Death.
AB - Neurotrophins, including nerve growth factor (NGF) and brain-derived neurotrophic
factor (BDNF), bind to their high-affinity receptors to promote neuronal survival
during brain development. One of the key downstream pathways is the phospholipase
C (PLC) pathway, which not only plays a central role in calcium release from
internal store but also in activation of TRPC channels coupled with neurotrophin
receptors. TRPC channels are required for the neurotrophin-mediated neuronal
protective effects. In addition, activation of TRPC channels is able to protect
neurons in the absence of neurotrophin. In some circumstances, TRPC channels
coupled with metabotropic glutamate receptor may mediate the excitotoxicity by
calcium overload. One of the key questions in the field is the channel gating
mechanisms; understanding of which would help design compounds to modulate the
channel properties. The development and identification of TRPC channel agonists
or blockers are promising and may unveil new therapeutic drugs for the treatment
of neurodegenerative diseases and epilepsy.
PMID- 28508313
TI - TRPC Channels and Stroke.
AB - TRPC channels play important roles in neuronal death/survival in ischemic stroke,
vasospasm in hemorrhagic stroke, thrombin-induced astrocyte pathological changes,
and also in the initiation of stroke by affecting blood pressure and
atherogenesis. TRPCs' unique channel characters and downstream pathways make them
possible new targets for stroke therapy. TRPC proteins have different functions
in different cell types. Considering TRPCs' extensive distribution in various
tissues and cell types, drugs targeting them could induce more complicated
effects. More specific agonists/antagonists and antibodies are required for
future study of TRPCs as potential targets for stroke therapy.
PMID- 28508314
TI - TRPC Channels and Alzheimer's Disease.
AB - Alzheimer's disease (AD) is the most common neurodegenerative disease in the
world. The "amyloid hypothesis" is one of the predominant hypotheses for the
pathogenesis of AD. Besides, tau protein accumulation, calcium homeostasis
disruption, and glial cell activation are also remarkable features in AD.
Recently, there are some reports showing that TRPC channels may function in AD
development, especially TRPC6. In this chapter, we will discuss the evidence for
the involvement of TRPC channels in Alzheimer's disease and the potential of
therapeutics for AD based on TRPC channels.
PMID- 28508316
TI - TRPC Channels and Neuron Development, Plasticity, and Activities.
AB - In this chapter, we mainly focus on the functions of TRPC channels in brain
development, including neural progenitor proliferation, neurogenesis, neuron
survival, axon guidance, dendritic morphology, synaptogenesis, and neural
plasticity. We also notice emerging advances in understanding the functions of
TRPC channels in periphery, especially their functions in sensation and
nociception in dorsal root ganglion (DRG). Because TRPC channels are expressed in
all major types of glial cells, which account for at least half of total cells in
the brain, TRPC channels may act as modulators for glial functions as well. The
future challenges for studying these channels could be (1) the detailed protein
structures of these channels, (2) their cell type-specific functions, (3)
requirement for their specific blockers or activators, and (4) change in the
channel conformation in the brain.
PMID- 28508318
TI - TRPC Channels and Epilepsy.
AB - Accumulating evidence suggest that TRPC channels play critical roles in various
aspects of epileptogenesis. TRPC1/4 channels are major contributors to
nonsynaptically derived epileptiform burst firing in the CA1 and the lateral
septum. TRPC7 channels play a critical role in synaptically derived epileptiform
burst firing. The reduction of spontaneous epileptiform bursting in the CA3 is
correlated to a reduction in pilocarpine-induced SE in vivo in TRPC7 knockout
mice. TRPC channels are also significant contributors to SE-induced neuronal cell
death. Although the pilocarpine-induced SE itself is not significantly reduced,
the SE-induced neuronal cell death is significantly reduced in the CA1 and the
lateral septum, indicating that TRPC1/4 channels directly contribute to SE
induced neuronal cell death. Genetic ablation of TRPC5 also reduces SE-induced
neuronal cell death in the CA1 and CA3 areas of the hippocampus.
PMID- 28508317
TI - TRPC Channels and Brain Inflammation.
AB - Nonresolving low-grade inflammation is supposed to underly the basis of chronic
disorders including cardiovascular diseases, cancer, diabetes, obesity, and
psychiatric disorders such as depression and Alzheimer's diseases. There is
increasing evidence suggesting that pathophysiology of psychiatric disorders is
related to the inflammatory responses mediated by microglial cells. Elevation of
intracellular Ca2+ is important for the activation of microglial cell functions,
including proliferation, release of NO, cytokines, and BDNF. It has been shown
that alteration of intracellular Ca2+ signaling underlies the pathophysiology of
psychiatric disorders, including depression. BDNF induces a sustained
intracellular Ca2+ elevation through the upregulation of the surface expression
of TRPC3 channels in rodent microglial cells. Microglial cells are able to
respond to BDNF, which may be important for the regulation of inflammatory
responses and may also be involved in the pathophysiology and/or the treatment of
psychiatric disorders. We also need to study the effect of proBDNF on microglial
cells especially by focusing on the TRPC channels.
PMID- 28508319
TI - TRPC Channels and Mental Disorders.
AB - Transient receptor potential canonical (TRPC) channels mediate the influx of
different types of cations through the cell membrane and are involved in many
functions of the organism. Evidences of involvement of TRPC channels in neuronal
development suggest that this family of proteins might play a role in certain
neurological disorders. As reported, knockout mice for different TRPC channels
show alterations in neuronal morphological and functional parameters, with
behavioral abnormalities, such as in exploratory and social behaviors. Although
mutations in TRPC channels could be related to mental/neurological disorders,
there are only a few cases reported in literature, indicating that this
correlation should be further explored. Nonetheless, other functional evidences
support the implication of these channels in neurological diseases. In this
chapter, we summarize the main findings relating TRPC channels to neurological
disorders, such as autism spectrum disorders, bipolar disorder, and intellectual
disability among others.
PMID- 28508315
TI - TRPC Channels and Parkinson's Disease.
AB - Parkinson's disease (PD) is a common neurodegenerative disorder, which involves
degeneration of dopaminergic neurons that are present in the substantia nigra
pars compacta (SNpc) region. Many factors have been identified that could lead to
Parkinson's disease; however, almost all of them are directly or indirectly
dependent on Ca2+ signaling. Importantly, though disturbances in Ca2+ homeostasis
have been implicated in Parkinson's disease and other neuronal diseases, the
identity of the calcium channel remains elusive. Members of the transient
receptor potential canonical (TRPC) channel family have been identified as a new
class of Ca2+ channels, and it could be anticipated that these channels could
play important roles in neurodegenerative diseases, especially in PD. Thus, in
this chapter we have entirely focused on TRPC channels and elucidated its role in
PD.
PMID- 28508320
TI - TRPC Channels and Cell Proliferation.
AB - TRPCs have been demonstrated to be widely expressed in different cancers. In
recent years, a number of studies closely investigated the roles of TRPCs in
cancer cells. Most of the results show that both mRNA and protein levels of TRPCs
significantly increase in cancer tissues compared with healthy controls. TRPCs
regulate Ca2+ homeostasis, contribute to cell cycle regulation and the
expression/activation of Ca2+-related factors, and thus play critical roles in
the proliferation of cancer cells. Therefore, TRPCs could act as potential drug
targets for cancer diagnosis and therapy.
PMID- 28508321
TI - TRPC Channels and Glioma.
AB - Glioma is the most common type of brain tumors and malignant glioma is extremely
lethal, with patients' 5-year survival rate less than 10%. Treatment of gliomas
poses remarkable clinical challenges, not only because of their particular
localization but also because glioma cells possess several malignant biological
features, including highly proliferative, highly invasive, highly angiogenic, and
highly metabolic aberrant. All these features make gliomas highly recurrent and
drug resistant. Finding new and effective molecular drug targets for glioma is an
urgent and critical task for both basic and clinical research. Recent studies
have proposed a type of non-voltage-gated calcium channels, namely, canonical
transient receptor potential (TRPC) channels, to be newly emerged potential drug
targets for glioma. They are heavily involved in the proliferation, migration,
invasion, angiogenesis, and metabolism of glioma cells. Abundant evidence from
both cell models and preclinical mouse models has demonstrated that inhibition of
TRPC channels shows promising anti-glioma effect. In this chapter, we will give a
comprehensive review on the current progress in the studies on TRPC channels and
glioma and discuss their potential clinical implication in glioma therapy.
PMID- 28508322
TI - Use patterns of first-line inhibitors of tyrosine kinase and time to change to
second-line therapy in chronic myeloid leukemia.
AB - Background Chronic myeloid leukemia (CML) has a low incidence but a high burden
of disease, and is treated with high-cost tyrosine kinase inhibitors (TKI).
Objective To determine the time from the start of a first-line TKI until it
passes to second-line, and to establish the reasons for the change of therapy
time. Setting Patients with Philadelphia-positive CML treated with some TKI.
Methods Retrospective cohort study, between January 1 2007 and July 31 2015, with
information obtained from medical records, the time to change initial drugs to
secondline therapy, and the reasons for change, were identified. Kaplan-Meier
survival analysis was carried out. Main outcome measure A change in therapy to
the secondline TKI and the final reason for the change of therapy. Results A
total of 247 patients treated were found in 22 cities in Colombia with a mean age
of 53.2 +/- 15.2 years. The drug most used as initial therapy was imatinib; 53.8%
of cases had to change to another TKI. 50% of patients changed therapy in 42
months, men in 24 and women in 67 months (95% CI 14.314-33.686; p = 0.001). Being
male (OR 2.23; 95% CI 1.291-3.854; p = 0.004) and receiving hydroxyurea (OR 3.65;
95% CI 1.601-8.326; p = 0.002) were associated with a higher probability of
switching to nilotinib or dasatinib, while receiving a new-generation TKI (OR
0.15; 95% CI 0.071-0.341; p < 0.001) reduced this risk. Conclusions A high
proportion of patients needed to change to a second line with nilotinib and
dasatinib management. It is necessary to obtain more real world evidence, to
improve the effectiveness, adherence and safety of the treatment.
PMID- 28508323
TI - The impact of pharmacy monitoring and intervention in patients receiving
intravenous heparin.
AB - Background Intravenous unfractionated heparin (IV UFH) has a narrow therapeutic
index and poses a high risk of bleeding. Objective To determine the impact of
pharmacy monitoring and intervention on adherence to and appropriate
implementation of IV UFH protocol. Setting A 438 bed hospital specializing in
cardiac services. Methods This is a retrospective chart review study. Pre
pharmacy intervention data were collected from November 2013 to January 2014 and
compared to post-pharmacy intervention data obtained between August 2014 and
October 2014. Patients were included if they received IV UFH for at least 24
hours. The first three daytime laboratory draws were collected for each patient
and analyzed using generalized estimating equations to quantify the association
between pharmacy monitoring and adherence to the institution's protocol. Main
outcome measures Designation of appropriate protocol, accurate selection of
initial infusion rate, timing of anti-Xa levels within 60 min of anticipated due
time, change of infusion rate within 120 min of laboratory result, and
appropriate adjustment of infusion rates. Results A total of 195 data points were
included. The initial selection of infusion rate and subsequent adjustments were
more appropriate in the post-intervention period with an odds ratio of 8.36 (95%
CI 2.41-29.01, p value = 0.0008), and 4.66 (95% CI 1.41-15.43, p value = 0.0118),
respectively. Conclusion The results of this study indicate that pharmacy
monitoring of IV UFH therapy has improved adherence to an institution's protocol
and is associated with more accurate selection of initial infusion rates and
adjustment of infusions based upon laboratory results.
PMID- 28508324
TI - Impact of clinical pharmacist intervention in anticoagulation clinic in Sudan.
AB - Background Many trials have compared anticoagulation management provided by a
pharmacist led anticoagulation clinic versus usual physician care showing the
role for clinical pharmacist in the management of anticoagulant therapy, and
demonstrating excellent outcomes. In Sudan, there is no published research
evaluating the role of pharmacist in providing pharmaceutical care for patients
taking warfarin. Objective The objective of the study is to assess the role of
clinical pharmacist intervention in warfarin patients compared to usual medical
care. Setting This study was conducted in Ahmed Gasim cardiac surgery and renal
transplant center warfarin clinic. Methods One hundred thirty-five patients were
randomly selected from adult patients on warfarin therapy The history of INR
records, and adverse effects for the past year, were recorded. Then patients'
warfarin dose adjustments according to INR, was done by the clinical pharmacist
for one year. Patients received continuous verbal education and written
information about warfarin. Main outcome measure The primary outcome for this
study was the INR control, while the secondary outcomes were the bleeding events
and hospitalization due to warfarin. Results After the clinical pharmacist
intervention there was significant (P < 0.01) improvement in INR control and a
significant (P < 0.05) reduction in incidence of bleeding after clinical
pharmacist intervention. Hospitalization due to warfarin related complications
(bleeding, high INR, low INR) was also significantly (P < 0.001) reduced.
Conclusion Clinical pharmacists intervention in warfarin therapy improve INR
control, reduce bleeding and hospitalization due to warfarin complications.
PMID- 28508325
TI - Preliminary Results of a Novel Algorithmic Method Aiming to Support Initial
Causality Assessment of Routine Pharmacovigilance Case Reports for Medication
Induced Liver Injury: The PV-RUCAM.
AB - INTRODUCTION: Data incompleteness in pharmacovigilance (PV) health records limits
the use of current causality assessment methods for drug-induced liver injury
(DILI). In addition to the inherent complexity of this adverse event, identifying
cases of high causal probability is difficult. OBJECTIVE: The aim was to evaluate
the performance of an improved, algorithmic and standardised method called the
Pharmacovigilance-Roussel Uclaf Causality Assessment Method (PV-RUCAM), to
support assessment of suspected DILI. Performance was compared in different
settings with regard to applicability and differentiation capacity. METHODS: A PV
RUCAM score was developed based on the seven sections contained in the original
RUCAM. The score provides cut-off values for or against DILI causality, and was
applied on two datasets of bona fide individual case safety reports (ICSRs)
extracted randomly from clinical trial reports and a third dataset of electronic
health records from a global PV database. The performance of PV-RUCAM
adjudication was compared against two standards: a validated causality assessment
method (original RUCAM) and global introspection. RESULTS: The findings showed
moderate agreement against standards. The overall error margin of no false
negatives was satisfactory, with 100% sensitivity, 91% specificity, a 25%
positive predictive value and a 100% negative predictive value. The Spearman's
rank correlation coefficient illustrated a statistically significant monotonic
association between expert adjudication and PV-RUCAM outputs (R = 0.93). Finally,
there was high inter-rater agreement (K w = 0.79) between two PV-RUCAM assessors.
CONCLUSION: Within the PV setting of a pharmaceutical company, the PV-RUCAM has
the potential to facilitate and improve the assessment done by non-expert PV
professionals compared with other methods when incomplete reports must be
evaluated for suspected DILI. Prospective validation of the algorithmic tool is
necessary prior to implementation for routine use.
PMID- 28508326
TI - The association of low penetrance genetic risk modifiers with colorectal cancer
in lynch syndrome patients: a systematic review and meta-analysis.
AB - Lynch syndrome (LS) is a highly penetrant inherited cancer predisposition
syndrome accounting for approximately 1000 cases of colorectal cancer (CRC) in
the UK annually. LS is characterised by autosomal dominant inheritance and
germline mutations in DNA mismatch repair genes. The penetrance is highly
variable and the reasons for this have not been fully elucidated. This study
investigates whether low penetrance genetic risk factors may result in phenotype
modification in LS patients. To conduct a systematic literature review and meta
analysis to assess the association between low penetrance genetic risk modifiers
and CRC in LS patients. A systematic review was conducted of the PubMed and
HuGENet databases. Eligibility of studies was determined by pre-defined criteria.
Included studies were analysed via the per-allele model and assessed by pooled
odds ratios and establishing 95% confidence intervals. Study heterogeneity was
assessed via Cochrane's Q statistic and I2 values. Publication bias was evaluated
with funnel plots. Subgroup analysis was conducted on gender. Statistical
software used was the Metafor package for the R programme version 3.1.3. Sixty
four polymorphisms were identified and sufficient data was available for analysis
of ten polymorphisms, with between 279 and 1768 CRC cases per polymorphism. None
demonstrated association with CRC risk in LS patients. However in sub-group
analysis the polymorphism rs16892766 (8q23.3) was significant in males (OR 1.53,
95% CI 1.12-2.10). The variable phenotype presentation of the disease still
remains largely unexplained, and further investigation is warranted. Other
factors may also be influencing the high variability of the disease, such as
environmental factors, copy number variants and epigenetic alterations.
Investigation into these areas is needed as well as larger and more definitive
studies of the polymorphisms analysed in this study.
PMID- 28508327
TI - Assessment of molecular markers demonstrates concordance between samples acquired
via stereotactic biopsy and open craniotomy in both anaplastic astrocytomas and
glioblastomas.
AB - The classification, treatment and prognosis of high-grade gliomas has been shown
to correlate with the expression of molecular markers (e.g. MGMT promotor
methylation and IDH1 mutations). Acquisition of tumor samples may be obtained via
stereotactic biopsy or open craniotomy. Between the years 2009 and 2013, 22
patients initially diagnosed with HGGs via stereotactic biopsy, that ultimately
underwent open craniotomy for resection of their tumor were prospectively
included in an institutional glioma database. MGMT promotor analysis was
performed using methylation-specific (MS)-PCR and IDH1R132H mutation analysis was
performed using immunohistochemistry. Three patients (13.7%) exhibited IDH1R132H
mutations in samples obtained via stereotactic biopsy. Tissue derived from
stereotaxic biopsy was demonstrated to have MGMT promotor methylation in ten
patients (45.5%), while a non-methylated MGMT promotor was demonstrated in ten
patients (45.5%); inconclusive results were obtained for the remaining two
patients (9%) within our cohort. The initial histologic grading, IDH1R132H
mutation and MGMT promotor methylation results were confirmed using samples
obtained during open craniotomy in all but one patient; here inconclusive MGMT
promotor analysis was obtained in contrast to that which was obtained via
stereotactic biopsy. Tumor samples acquired via stereotactic biopsy provide
accurate information with regard to clinically relevant molecular markers that
have been shown to impact patient care decisions. The profile of markers analyzed
in our cohort was nearly concordant between those samples obtained via
stereotactic biopsy or open craniotomy thereby suggesting that clinical decisions
may be based on the molecular profile of the tumor samples obtained via
stereotactic biopsy.
PMID- 28508328
TI - MiR-424 functions as a tumor suppressor in glioma cells and is down-regulated by
DNA methylation.
AB - Glioma is one of the most lethal malignancies, and increasing reports revealed
that microRNAs (miRNAs), a class of small non-coding RNAs, play a critical role
in the development and pathology of human gliomas. MiR-424 has been found to be
dysregulated in many different types of human cancers. However, the clinical
significance and function of miR-424 in glioma remains unclear. Here, based on
RTq-PCR analysis in 148 clinical specimens, we found miR-424 expression was
significantly decreased in glioma tumor tissues than in adjacent non-neoplastic
brain tissues, and decreased miR-424 expression was associated with glioma KPS (P
= 0.009) and high grades (P = 0.029). In vitro cellular function assays further
revealed that miR-424 inhibited cell invasion and migration, and promoted cell
apoptosis. In addition, based on DNA methylation analysis on clinical specimens
and cell lines, we found miR-424 promoter CpG island was frequently methylated
and correlated with glioma high grades (P = 0.035) and IDH mutation status (P =
0.042). Moreover, the promoter CpG island was demethylated by 5-aza-2'
deoxycytidine treatment in a time-dependent manner and the expression levels of
miR-424 were gradually induced and increased. Taken together, our data suggest
that the promoter region CpG island methylation is associated with tumor
suppressive miR-424 silencing and the pathology of human gliomas.
PMID- 28508329
TI - Long Non-Coding RNA SNHG6 as a Potential Biomarker for Hepatocellular Carcinoma.
AB - Long Non-coding RNAs (lncRNAs) refer to all non-protein coding transcripts longer
than 200 nucleotides. Their critical roles in different biological pathways have
been already well established. Altered expression of lncRNAs can be involved in
the cancer initiation and/or progression. Since patients with hepatocellular
carcinoma (HCC) are usually diagnosed in late stages, developing diagnostic
methods seems to be essential. In this study, the expression levels of different
lncRNAs were systematically analysed in different genomic and transcriptome
datasets. The analyses showed that SNHG6 is among the lncRNAs with distinctive
dysregulation of expression and copy number variation in HCC tumors compared with
normal tissues. The results also suggest that the dysregulation of SNHG6 is
highly cancer type specific. Through co-occurrence analyses, we found that SNHG6
and its related co-expressed genes on 8q are involved in the structural integrity
of ribosome and translation. This comprehensive in silico analysis, provides a
resource for investigating SNHG6 in hepatocellular carcinoma and lays the
groundwork for design of next researches.
PMID- 28508330
TI - Mediators of Weight Loss Maintenance in the Keep It Off Trial.
AB - Background: An important step toward enhancing the efficacy of weight loss
maintenance interventions is identifying the pathways through which successful
interventions such as the Keep It Off trial have worked. Purpose: This study
aimed to assess the viability of mediated relationships between the Keep It Off
Guided intervention, conceptually and empirically grounded potential mediators,
and weight. Repeated measurement of mediators and weight enabled documentation of
the temporal ordering of intervention delivery and changes in mediators and in
weight among participants randomized to the Guided intervention or Self-Directed
comparison group. Methods: Total, direct, and indirect effects of the Guided
intervention on weight change were calculated and tested for significance.
Indirect effects were comprised of the influence of the intervention on three
change scores for each mediator and the relationship between mediator changes and
weight changes 6 months later. Results: Guided intervention participants regained
about 2% less weight over 24 months than Self-Directed participants. Starting
daily self-weighing accounted for the largest share of this difference, followed
by not stopping self-weighing. Conclusions: Daily self-weighing mediated 24-month
weight loss maintenance. Trial Registration Number: The trial is registered with
ClinicalTrials.gov (Identifier: NCT00702455
www.clinicaltrials.gov/ct2/show/NCT00702455).
PMID- 28508331
TI - Is pesticide sorption by constructed wetland sediments governed by water level
and water dynamics?
AB - Constructed wetlands (CWs) are used to reduce the pesticide inputs from tile
drainage or run-off to surface water. Their effectiveness appears variable and
remains to be better characterized and understood. The aim of this study was to
assess the influences of two hydraulic parameters (i.e., dynamics and water
level) on the sorption process occurring in CWs. Then, two solid/liquid ratios
were studied (1/1 and 1/5) to mimic the water level variation in the field, and
two agitation speeds were used (none and gentle agitation) to simulate different
water dynamics (stagnation and flow pass, respectively). Sorption kinetics and
isotherms were obtained for four pesticides with contrasting properties. The
pesticide adsorption coefficients were classified as follows: boscalid (BSC) >
cyproconazole (CYP) > isoproturon (IPU) ~ dimethachlor (DMT) at any ratio or
agitation, in agreement with their water solubilities and K ow values. The effect
of the solid/liquid ratio was evidenced for all conditions. Indeed, the
adsorption equilibrium time was reached more quickly for the 1/1 ratio (24-72 h)
than for the 1/5 ratio (96-120 h). In addition, the adsorption coefficients (K
fads) were larger for the 1/1 ratio (1.8-11.2 L kg-1) than for the 1/5 ratio (1.0
5.9 L kg-1). The agitation effect was more evidenced for the 1/5 ratio and for
the more hydrophobic molecules, such as BSC and CYP, for which adsorption
equilibrium time was never reached with agitation (>120 h), while it was reached
at 96 h without agitation. Moreover, the K fads values were larger with agitation
than without agitation for BSC and CYP, whereas they were similar for the two
agitations for IPU and DMT. Our results demonstrated that the hydrodynamic
function of CWs could influence pesticide sorption with variable effects
according to the molecular properties and consequently influence the mitigation
effect of CWs throughout the year.
PMID- 28508332
TI - Occurrence of diazepam and its metabolites in wastewater and surface waters in
Beijing.
AB - Occurrence of diazepam and its metabolites, nordiazepam, temazepam, and oxazepam
in the water environment in Beijing was investigated. Samples were collected from
four rivers flowing through the city and from all the thirteen sewage treatment
plants in the urban area. Average influent concentrations of diazepman,
temazepam, and oxazepam in 2013 summer ranged from 0.9 to 7.1, 1.5 to 3.4, and
2.9 to 12.4 ng L-1, respectively, whereas nordiazepam concentrations were below
quantification limit on the majority of sampling dates. No significant seasonal
variation in influent concentrations was observed. Removal during treatment was
low for diazepman (<50%), temazepam (<20%), and oxazepam (<20%), consistent with
previous findings reported in the literature. Wastewater-based epidemiology
approach was applied to back-calculate population size-normalized diazepam
consumption (using temazepam as biomarker) in Beijing, which was found to be at
least 3.8 times more of the national average. Diazepam, temazepam, and oxazepam
were widely detected in surface waters, with concentrations greater than
concentrations in sewage influents at many sampling points, strongly indicating
direct discharge of wastewater of high diazepam concentrations into the surface
waters in the city.
PMID- 28508333
TI - Levels and risk assessment of metals in sediment and fish from Chaohu Lake, Anhui
Province, China.
AB - Chaohu Lake is the fifth largest freshwater lake in China, which tolerates
substantial amount of anthropogenic discharge from surrounding cities that
resulting in the degradation of water and damage of aquatic ecosystem. Metal
analysis of sediment and aquatic organisms can provide important information on
the environmental contamination and potential impact of aquatic food consumption.
Thus, the concentrations of Cu, Pb, Zn, Cr, Cd, As, and Hg in sediment and fish
from Chaohu Lake were analyzed with inductively coupled plasma mass spectrometry
and atomic fluorescence spectrometry. The mean content of Cu, Pb, Zn, Cr, Cd, As,
and Hg in the sediment samples were 27.4 +/- 6.3, 40.5 +/- 12.3, 136.8 +/- 65.5,
68.5 +/- 9.1, 0.357 +/- 0.141, 10.8 +/- 1.7, and 0.117 +/- 0.049 mg/kg,
respectively. The results were compared with background values and evaluation
methods, to characterize the potential ecological risk. The concentrations of Cu,
Pb, Zn, Cr, Cd, As, and Hg in the fish muscle samples were 1.68-5.31, 0.078-0.31,
15.55-372.98, 0.31-0.93, 0.001-0.033, 0.29-1.03, and 0.04-0.197 mg kg-1 of dry
mass, respectively. Most of the concentrations of the studied metals in muscles
were found to be below the safe limits; however, the concentration of inorganic
As (10% of total As) in two specimens exceeded the maximum allowance in fish. The
ecological risk evaluation showed that the metals in sediment posed low to medium
risk. The health risk assessment suggested that the consumption of fish from
Chaohu Lake is currently safe with respect to the metals.
PMID- 28508334
TI - A survey of mycotoxin contamination and chemical composition of distiller's dried
grains with solubles (DDGS) imported from the USA into Saudi Arabia.
AB - Distiller's dried grains with solubles (DDGS) is a source of nutritional
feedstuff for poultry farmers and industry. The DDGS is a by-product of ethanol
industry and an economical feed source of energy, amino acids, crude fiber,
minerals, and vitamins. The use of DDGS as a feed ingredient is a novel idea and
little information is available on its dietary composition. Many factors such as
the type of plants, locality, year of production, and the conditions during
distillation process affect the chemical composition of DDGS. In this paper, the
chemical composition and the presence of mycotoxin in DDGS imported from the USA
into Saudi Arabia as a feedstuff for poultry have been documented.
PMID- 28508335
TI - Toxic potential of organic constituents of submicron particulate matter (PM1) in
an urban road site (Barcelona).
AB - Atmospheric particulate matter (PM) is a recognized risk factor contributing to a
number of diseases in human populations and wildlife globally. Organic matter is
a major component of PM, but its contribution to overall toxicity of PM has not
been thoroughly evaluated yet. In the present work, the biological activity of
organic extracts from PM1 (particles with less than 1 MUm of aerodynamic
diameter) collected from an urban road site in the centre of Barcelona (NE Spain)
was evaluated using a yeast-based assay (AhR-RYA) and different gene expression
markers in zebrafish embryos. Dioxin-like activity of the extracts correlated to
primary emissions from local traffic exhausts, reflecting weekday/weekend
alternance. Expression levels of cyp1a and of gene markers for key cellular
processes and development (ier2, fos) also correlated to vehicle emissions,
whereas expression of gene markers related to antioxidant defence and endocrine
effects (gstal, hao1, ttr) was strongly reduced in samples with strong
contribution from regional air masses with aged secondary organic species or with
strong influence of biomass burning emissions. Our data suggest that the toxic
potential of PM1 organic chemical constituents strongly depends on the emission
sources and on the process of ageing from primary to secondary organic aerosols.
PMID- 28508336
TI - The impacts of non-renewable and renewable energy on CO2 emissions in Turkey.
AB - As a result of great increases in CO2 emissions in the last few decades, many
papers have examined the relationship between renewable energy and CO2 emissions
in the energy economics literature, because as a clean energy source, renewable
energy can reduce CO2 emissions and solve environmental problems stemming from
increases in CO2 emissions. When one analyses these papers, he/she will observe
that they employ fixed parameter estimation methods, and time-varying effects of
non-renewable and renewable energy consumption/production on greenhouse gas
emissions are ignored. In order to fulfil this gap in the literature, this paper
examines the effects of non-renewable and renewable energy on CO2 emissions in
Turkey over the period 1970-2013 by employing fixed parameter and time-varying
parameter estimation methods. Estimation methods reveal that CO2 emissions are
positively related to non-renewable energy and renewable energy in Turkey. Since
policy makers expect renewable energy to decrease CO2 emissions, this paper
argues that renewable energy is not able to satisfy the expectations of policy
makers though fewer CO2 emissions arise through production of electricity using
renewable sources. In conclusion, the paper argues that policy makers should
implement long-term energy policies in Turkey.
PMID- 28508337
TI - Natural radionuclide dose and lifetime cancer risk due to ingestion of fish and
water from fresh water reservoirs near the proposed uranium mining site.
AB - Ten sampling locations in Nagarjuna Sagar Dam have been selected to assess the
suitability of the reservoir water for human consumption. The sediment, water,
and fish samples were collected and analyzed for radionuclide (238U, 232Th,
210Po, 226Ra, 210Pb) and physicochemical parameters like pH, TOC, total hardness,
alkalinity, DO, cation exchange capacity, and particle size. The spatial
variations among the radionuclides (238U, 232Th, 210Po, 226Ra, 210Pb) in water
and bottom sediments of Nagarjuna Sagar Dam were determined. The uranium
concentration in the sediment and water was in BDL (<0.5 ppb). The maximum
permissible limits in water samples of the analyzed radionuclides are 238U-10
Bq/l, 210Po-0.1 Bq/l, 226Ra-1 Bq/l, and 210Pb-0.1 Bq/l. The radionuclides in our
water samples were approximately 50 times far below the recommended limit. The
ingestion of water and fish would not pose any significant radiological impact on
health or cancer risk to the public, implicating that the fishes from Nagarjuna
Sagar Dam reservoir are safe for human consumption except the fisherman
community.
PMID- 28508339
TI - Induction of hibernation-like hypothermia by central activation of the A1
adenosine receptor in a non-hibernator, the rat.
AB - Central adenosine A1-receptor (A1AR)-mediated signals play a role in the
induction of hibernation. We determined whether activation of the central A1AR
enables rats to maintain normal sinus rhythm even after their body temperature
has decreased to less than 20 degrees C. Intracerebroventricular injection of an
adenosine A1 agonist, N6-cyclohexyladenosine (CHA), followed by cooling decreased
the body temperature of rats to less than 20 degrees C. Normal sinus rhythm was
fundamentally maintained during the extreme hypothermia. In contrast, forced
induction of hypothermia by cooling anesthetized rats caused cardiac arrest.
Additional administration of pentobarbital to rats in which hypothermia was
induced by CHA also caused cardiac arrest, suggesting that the operation of some
beneficial mechanisms that are not activated under anesthesia may be essential to
keep heart beat under the hypothermia. These results suggest that central A1AR
mediated signals in the absence of anesthetics would provide an appropriate
condition for maintaining normal sinus rhythm during extreme hypothermia.
PMID- 28508338
TI - Fluid Balance in Team Sport Athletes and the Effect of Hypohydration on
Cognitive, Technical, and Physical Performance.
AB - Sweat losses in team sports can be significant due to repeated bursts of high
intensity activity, as well as the large body size of athletes, equipment and
uniform requirements, and environmental heat stress often present during training
and competition. In this paper we aimed to: (1) describe sweat losses and fluid
balance changes reported in team sport athletes, (2) review the literature
assessing the impact of hypohydration on cognitive, technical, and physical
performance in sports-specific studies, (3) briefly review the potential
mechanisms by which hypohydration may impact team sport performance, and (4)
discuss considerations for future directions. Significant hypohydration (mean
body mass loss (BML) >2%) has been reported most consistently in soccer. Although
American Football, rugby, basketball, tennis, and ice hockey have reported high
sweating rates, fluid balance disturbances have generally been mild (mean BML
<2%), suggesting that drinking opportunities were sufficient for most athletes to
offset significant fluid losses. The effect of hydration status on team sport
performance has been studied mostly in soccer, basketball, cricket, and baseball,
with mixed results. Hypohydration typically impaired performance at higher levels
of BML (3-4%) and when the method of dehydration involved heat stress. Increased
subjective ratings of fatigue and perceived exertion consistently accompanied
hypohydration and could explain, in part, the performance impairments reported in
some studies. More research is needed to develop valid, reliable, and sensitive
sport-specific protocols and should be used in future studies to determine the
effects of hypohydration and modifying factors (e.g., age, sex, athlete caliber)
on team sport performance.
PMID- 28508342
TI - Current strategies in the diagnosis of endometrial cancer.
AB - PURPOSE: Endometrial cancer is the most common gynecological malignancy in
developed countries. There are no uniform recommendations for endometrial cancer
screening in the general population. Therefore, it is of paramount importance
that the primary physician profoundly understands, and is familiar with the
methods for prevention and early detection of endometrial cancer. The aim of this
review is to provide the primary physician with a toolbox to reach these goals.
METHODS: We performed a systemic review to summarize the current strategies to
diagnose and prevent endometrial cancer. Many published articles from the last
years were identified and included. RESULTS: A systematic review that summarizes
the important subjects in the diagnosis and prevention of endometrial cancer.
CONCLUSION: Maintaining a high index of suspicion and obtaining endometrial
biopsies from all suspected patients is the key for achieving a timely diagnosis.
PMID- 28508340
TI - Comparative effects of sertraline, haloperidol or olanzapine treatments on
ketamine-induced changes in mouse behaviours.
AB - Effects of sertraline, haloperidol or olanzapine administration on ketamine
induced behaviours in mice were examined. The aim was to ascertain the degree of
reversal of such behaviours by sertraline, and compare its effectiveness to
haloperidol and olanzapine. Ten-week old mice (N = 120) were equally divided into
main groups; 1 (open-field, radial-arm maze and elevated plus maze {EPM} tests),
and 2 (social interaction test). Mice in each main group were assigned into six
groups of ten (n = 10) each. Group 1 received intraperitoneal (i.p) injection of
vehicle, while groups 2-6 received i.p ketamine at 15 mg/kg daily for 10 days.
From day 11 to 24, mice in group 1 (vehicle) were given distilled water (i.p at 2
ml/kg and oral at 10 ml/kg), group 2 (ketamine control) received daily i.p
ketamine and oral distilled water; while animals in groups 3-6 received daily
i.p. ketamine and oral haloperidol (4 mg/kg), olanzapine (2 mg/kg), or one of two
doses of sertraline (SERT) (2.5 or 5 mg/kg), respectively. Treatments were
administered daily, and behaviours assessed on days 11 and 24. Results showed
that repeated ketamine administration caused hyperlocomotion, increased self
grooming, memory loss and social withdrawal. Administration of sertraline (both
doses), haloperidol, and olanzapine reversed ketamine-induced behavioural
changes. However, in the EPM, sertraline and olanzapine were anxiolytic, while
haloperidol was anxiogenic. Sertraline's effect on behaviours tested was
comparable to olanzapine and better than haloperidol. In conclusion, this study
shows that sertraline's ability to counteract ketamine-induced behavioural
changes in mice is comparable to known antipsychotics.
PMID- 28508343
TI - Cytomegalovirus infection in pregnancy.
AB - PURPOSE: Due to the severe risk of long-term sequelae, prenatal cytomegalovirus
infection is of particular importance amongst intrauterine viral infections. This
review summarizes the current knowledge about CMV infection in pregnancy.
METHODS: A search of the Medline and Embase database was done for articles about
CMV infection in pregnany. We performed a detailed review of the literature in
view of diagnosis, epidemiology and management of CMV infection in pregnancy.
RESULTS: The maternal course of the infection is predominantly asymptomatic; the
infection often remains unrecognized until the actual fetal manifestation.
Typical ultrasound signs that should arouse suspicion of intrauterine CMV
infection can be distinguished into CNS signs such as ventriculomegaly or
microcephaly and extracerebral infection signs such as hepatosplenomegaly or
hyperechogenic bowel. Current treatment strategies focus on hygienic measures to
prevent a maternal CMV infection during pregnancy, on maternal application of
hyperimmunoglobulines to avoid materno-fetal transmission in case of a maternal
seroconversion, and on an antiviral therapy in case the materno-fetal
transmission have occurred. CONCLUSION: CMV infection in pregnancy may result in
a severe developmental disorder of the newborn. This should be taken into account
in the treatment of affected and non-affected pregnant women.
PMID- 28508341
TI - Mitochondrial DNA levels in Huntington disease leukocytes and dermal fibroblasts.
AB - Huntington disease (HD) is an inherited neurodegenerative disorder caused by
mutations in the huntingtin gene. Involvement of mitochondrial dysfunctions in,
and especially influence of the level of mitochondrial DNA (mtDNA) on,
development of this disease is unclear. Here, samples of blood from 84 HD
patients and 79 controls, and dermal fibroblasts from 10 HD patients and 9
controls were analysed for mtDNA levels. Although the type of mitochondrial
haplogroup had no influence on the mtDNA level, and there was no correlation
between mtDNA level in leukocytes in HD patients and various parameters of HD
severity, some considerable differences between HD patients and controls were
identified. The average mtDNA/nDNA relative copy number was significantly higher
in leukocytes, but lower in fibroblasts, of symptomatic HD patients relative to
the control group. Moreover, HD women displayed higher mtDNA levels in leukocytes
than HD men. Because this is the largest population analysed to date, these
results might contribute to explanation of discrepancies between previously
published studies concerning levels of mtDNA in cells of HD patients. We suggest
that the size of the investigated population and type of cells from which DNA is
isolated could significantly affect results of mtDNA copy number estimation in
HD. Hence, these parameters should be taken into consideration in studies on
mtDNA in HD, and perhaps also in other diseases where mitochondrial dysfunction
occurs.
PMID- 28508344
TI - Vaginal hysterectomy versus laparoscopically assisted vaginal hysterectomy for
large uteri between 280 and 700 g: a randomized controlled trial.
AB - OBJECTIVE: To compare surgical outcomes, postoperative complications and costs
between vaginal hysterectomy and laparoscopically assisted vaginal hysterectomy
in cases of large uteri. METHODS: Prospective randomized controlled trial done at
Ain Shams University Maternity Hospital, where 50 patients were recruited and
divided into two equal groups (each 25 patients). First group underwent vaginal
hysterectomy, and the second underwent laparoscopically assisted vaginal
hysterectomy. RESULTS: Patient characteristics were similar in both groups. As
for surgical outcomes, estimated intraoperative blood loss (P = 0.90), operative
time (P = 0.48), preoperative hemoglobin (P = 0.09), postoperative hemoglobin (P
= 0.42), and operative complications (P = 1.0) did not differ between the two
groups. The hospital costs (converted from Egyptian pound to U.S. dollars) were
significantly higher in case of LAVH group [VH: $1060.86 ($180.09) versus LAVH:
$1560.5 ($220.57), P value <0.001]. No significant difference exists in the
duration of postoperative hospital stay between the two groups [VH: 49.92 h
(28.50) versus LAVH: 58.56 (27.78), P = 0.28] or the actual uterine weight
measured postoperatively [VH: 350.72 g (71.78) versus LAVH: 385.96 g (172.52), P
= 0.35]. CONCLUSION: Both vaginal hysterectomy and laparoscopically assisted
vaginal hysterectomy are safe procedures in cases of large uteri with no
significant difference between them except in terms of costs as VH appears to be
more cost effective. CLINICAL TRIALS.GOV: NCT02826304.
PMID- 28508345
TI - Deep monocular 3D reconstruction for assisted navigation in bronchoscopy.
AB - PURPOSE: In bronchoschopy, computer vision systems for navigation assistance are
an attractive low-cost solution to guide the endoscopist to target peripheral
lesions for biopsy and histological analysis. We propose a decoupled deep
learning architecture that projects input frames onto the domain of CT
renderings, thus allowing offline training from patient-specific CT data.
METHODS: A fully convolutional network architecture is implemented on GPU and
tested on a phantom dataset involving 32 video sequences and [Formula: see
text]60k frames with aligned ground truth and renderings, which is made available
as the first public dataset for bronchoscopy navigation. RESULTS: An average
estimated depth accuracy of 1.5 mm was obtained, outperforming conventional
direct depth estimation from input frames by 60%, and with a computational time
of [Formula: see text]30 ms on modern GPUs. Qualitatively, the estimated depth
and renderings closely resemble the ground truth. CONCLUSIONS: The proposed
method shows a novel architecture to perform real-time monocular depth estimation
without losing patient specificity in bronchoscopy. Future work will include
integration within SLAM systems and collection of in vivo datasets.
PMID- 28508347
TI - Does Helicobacter pylori infection increase the risk of adult-onset asthma?
PMID- 28508346
TI - Testosterone insulin-like effects: an in vitro study on the short-term metabolic
effects of testosterone in human skeletal muscle cells.
AB - PURPOSE: Testosterone by promoting different metabolic pathways contributes to
short-term homeostasis of skeletal muscle, the largest insulin-sensitive tissue
and the primary site for insulin-stimulated glucose utilization. Despite
evidences indicate a close relationship between testosterone and glucose
metabolism, the molecular mechanisms responsible for a possible testosterone
mediated insulin-like effects on skeletal muscle are still unknown. METHODS: Here
we used undifferentiated proliferating or differentiated human fetal skeletal
muscle cells (Hfsmc) to investigate the short-term effects of testosterone on the
insulin-mediated biomolecular metabolic machinery. GLUT4 cell expression,
localization and the phosphorylation/activation of AKT, ERK, mTOR and GSK3beta
insulin-related pathways at different time points after treatment with
testosterone were analyzed. RESULTS: Independently from cells differentiation
status, testosterone, with an insulin-like effect, induced Glut4-mRNA expression,
GLUT4 protein translocation to the cytoplasmic membrane, while no effect was
observed on GLUT4 protein expression levels. Furthermore, testosterone treatment
modulated the insulin-dependent signal transduction pathways inducing a rapid and
persistent activation of AKT, ERK and mTOR, and a transient inhibition of
GSK3beta. T-related effects were shown to be androgen receptor dependent.
CONCLUSION: All together our data indicate that testosterone through the
activation of non-genomic pathways, participates in skeletal muscle glucose
metabolism by inducing insulin-related effects.
PMID- 28508348
TI - Cost analysis of minimally invasive radical hysterectomy for cervical cancer
performed by a single surgeon in an Italian center: an update in gynecologic
oncological field.
AB - The objective of this study is to perform an economic analysis and examine the
influence of procedural volume of our hospital, evaluating the accounting systems
of Robotic radical hysterectomy (RRH) vs Laparoscopic radical hysterectomy (TLRH)
in patients with cervical carcinoma, due to the costs widely variable and lack in
literature. Costs were collected prospectively, from March 2010 to March 2016.
Direct costs were determined by examining the overall medical pathway for each
type of intervention. 52 patients with cervical carcinoma, which were matched by
age, body mass index, tumor size, International Federation of Gynecology and
Obstetrics (FIGO) stage, comorbidity, previous neoadjuvant chemotherapy,
histology type, and tumor grade to obtain homogeneous samples. Surgical time was
similar for both the groups. RRH was associated with a significantly less (EBL)
estimated blood loss (P = 0.000). The overall median length of follow-up was of
59 months. The cost of the robot-specific supplies was ?2705 per intervention.
When considering overall medical surgical care, the patient treatment average
cost of an RRH was ?5650,31 with an hospital stay (HS) of 3.58 days (SD +/- 1) vs
?3750.86 for TRLH, with an HS of 4.27 days (SD +/- 1.79). Our results are similar
to Finnish data; the costs of robot-assisted hysterectomies were 1.5 times higher
than TLRH. The main drivers of additional costs are robotic disposable
instruments, which are not compensated by the hospital room costs and by an
experienced team staff. Implementation of strategies to reduce the cost of
robotic instrumentation is due. RRH resulted less expensive than robotic simple
hysterectomy for benign conditions.
PMID- 28508349
TI - The Contemporary Role of Stents and Angioplasty for the Treatment of
Infrapopliteal Disease in Critical Limb Ischemia.
AB - PURPOSE OF REVIEW: Critical limb ischemia (CLI) is associated with significant
morbidity, mortality, and increased health care expenses. Revascularization has a
central role in the treatment of CLI. Following publication of BASIL (bypass
versus angioplasty in severe ischemia of the leg) trial a decade ago, an
"endovascular first" approach had gained momentum and the technologies available
for endovascular therapy have exponentially increased. Both the development of
technology and technique, highlighted in this review, have allowed operators to
treat complex infrapopliteal lesions which are central to CLI pathology. RECENT
FINDINGS: The role of atherectomy remains controversial but for calcified lesions
it has become an accepted adjunctive tool for plaque modification. The place of
drug delivery technologies requires further trials. The use of a drug-coated
balloon (DCB) makes intuitive sense; however, choice of excipient, lower limit of
vessel size, and impact on remodeling and thrombosis remain uncertain. The
optimal treatment of infrapopliteal disease remains an area of active
investigation. The endpoints in CLI trials continue to be challenging and
calibration of patency in relation to wound healing remains a moving target. In
addition, unaccounted variables continue to confound interpretation of CLI trials
including quality and nature of wound care, status of pedal-plantar loop patency,
and management of underlying diabetes and other comorbidities. In summary, these
challenges will also need to be addressed as the CLI field continues to mature in
the twenty-first century.
PMID- 28508350
TI - Targeted Nuclear Imaging Probes for Cardiac Amyloidosis.
AB - PURPOSE OF REVIEW: The aim of the present manuscript is to review the latest
advancements of radionuclide molecular imaging in the diagnosis and prognosis of
individuals with cardiac amyloidosis. RECENT FINDINGS: 99mTechnetium labeled bone
tracer scintigraphy had been known to image cardiac amyloidosis, since the 1980s;
over the past decade, bone scintigraphy has been revived specifically to diagnose
transthyretin cardiac amyloidosis. 18F labeled and 11C labeled amyloid binding
radiotracers developed for imaging Alzheimer's disease, have been repurposed
since 2013, to image light chain and transthyretin cardiac amyloidosis.
99mTechnetium bone scintigraphy for transthyretin cardiac amyloidosis, and
amyloid binding targeted PET imaging for light chain and transthyretin cardiac
amyloidosis, are emerging as highly accurate methods. Targeted radionuclide
imaging may soon replace endomyocardial biopsy in the evaluation of patients with
suspected cardiac amyloidosis. Further research is warranted on the role of
targeted imaging to quantify cardiac amyloidosis and to guide therapy.
PMID- 28508351
TI - Native and Non-native Speakers' Brain Responses to Filled Indirect Object Gaps.
AB - We examined native and non-native English speakers' processing of indirect object
wh-dependencies using a filled-gap paradigm while recording event-related
potentials (ERPs). The non-native group was comprised of native German-speaking,
proficient non-native speakers of English. Both participant groups showed
evidence of linking fronted indirect objects to the subcategorizing verb when
this was encountered, reflected in an N400 component. Evidence for continued
filler activation beyond the verb was seen only in the non-native group, in the
shape of a prolonged left-anterior negativity. Both participant groups showed
sensitivity to filled indirect object gaps reflected in a P600 response, which
was more pronounced and more globally distributed in our non-native group. Taken
together, our results indicate that resolving indirect object dependencies is a
two-step process in both native and non-native sentence comprehension, with
greater processing cost incurred in non-native compared to native comprehension.
PMID- 28508353
TI - What matters when judging intentionality-moral content or normative status?
Testing the rational scientist model of the side-effect.
AB - Previous work has demonstrated a "side-effect effect," such that intentionality
is more likely to be attributed to agents who bring about negatively valenced as
opposed to positively valenced side effects. The rational-scientist model
explains this by suggesting that norm-violating side effects are more informative
for inferring intentionality than norm-conforming side effects. In the present
study we reexamined this account, addressing limitations of previous empirical
tests (e.g., Uttich & Lombrozo, Cognition 116: 87-100, 2010). Side-effect valence
and norm status were manipulated factorially, enabling an examination of the
impact of norm status on intentionality judgments in both positively and
negatively valenced side effects. Additionally, the impact of side-effect norm
status on the perceived valences of side effects and agents was examined. Effects
of norm status were found for both positive and negative side effects. Violation
of an ostensibly neutral norm led to negative perceptions of the side effect.
However, a norm status effect on intentionality judgments persisted when these
effects were controlled. These results support the view that the side-effect
effect is the result of the rational use of social-cognitive evidence.
PMID- 28508352
TI - Pediatric precursor B acute lymphoblastic leukemia: are T helper cells the
missing link in the infectious etiology theory?
AB - Precursor B acute lymphoblastic leukemia (BCP-ALL), the most common childhood
malignancy, arises from an expansion of malignant B cell precursors in the bone
marrow. Epidemiological studies suggest that infections or immune responses to
infections may promote such an expansion and thus BCP-ALL development.
Nevertheless, a specific pathogen responsible for this process has not been
identified. BCP-ALL cells critically depend on interactions with the bone marrow
microenvironment. The bone marrow is also home to memory T helper (Th) cells that
have previously expanded during an immune response in the periphery. In secondary
lymphoid organs, Th cells can interact with malignant cells of mature B cell
origin, while such interactions between Th cells and malignant immature B cell in
the bone marrow have not been described yet. Nevertheless, literature supports a
model where Th cells-expanded during an infection in early childhood-migrate to
the bone marrow and support BCP-ALL cells as they support normal B cells. Further
research is required to mechanistically confirm this model and to elucidate the
interaction pathways between leukemia cells and cells of the tumor
microenvironment. As benefit, targeting these interactions could be included in
current treatment regimens to increase therapeutic efficiency and to reduce
relapses.
PMID- 28508354
TI - Patient and Public Preferences for Treatment Attributes in Parkinson's Disease.
AB - BACKGROUND: Patient and public preferences for therapeutic outcomes or medical
technologies are often elicited, and discordance between the two is frequently
reported. OBJECTIVE: Our main objective was to compare patient and public
preferences for treatment attributes in Parkinson's disease (PD). METHODS: A
representative sample from Dutch PD patients and the general public were invited
to complete a best-worst scaling case 2 experiment consisting of six health
related outcomes and one attribute describing the specific treatment (brain
surgery, pump, oral medication). Data were analyzed using mixed logit models, and
attribute impact was estimated and compared between populations (and population
subgroups). RESULTS: Both the public (N = 276) and patient (N = 198) populations
considered treatment modality the most important attribute, although patients
assigned higher relative importance. Both groups assigned high disutility to pump
infusion and brain surgery and preferred drug treatment. Most health outcomes
were valued equally by patients and the public, with the exception of reducing
dizziness (more important to the public) and improving slow movement (more
important to patients). DISCUSSION: Although these data do not support definite
conclusions on whether patients are less likely to undergo invasive treatments,
the (predicted) choice probability of undergoing brain surgery or having pump
infusion technology would be low based on the (un)desirability of the attribute
levels. Patients with PD might have adapted to their condition and are not
willing to undergo advanced treatments in order to receive health improvements.
Both public and patient preferences entail information that is potentially
relevant for decision makers, and patient preferences can inform decision makers
about the likelihood of adaptation to a specific condition.
PMID- 28508355
TI - Neuroproteomics Studies: Challenges and Updates.
AB - The Human Genome Project in 2003 has resulted in the complete sequence of ~99% of
the human genome paving the road for the Human Proteome Project (HPP) assessing
the full characterization of the translated protein map of the 20,300 protein
coding genes. Consequently, the emerging of the proteomics field has successfully
been adopted as the method of choice for the proteome characterization.
Proteomics is a term that is used to encompass multidisciplinary approaches
combining different technologies that aim to study the entire spectrum of protein
changes at a specific physiological condition. Proteomics research has shown
excellent outcomes in different fields, among which is neuroscience; however, the
complexity of the nervous systems necessitated the genesis of a new subdiscipline
of proteomics termed as "neuroproteomics." Neuroproteomics studies involve
assessing the quantitative and qualitative aspects of nervous system components
encompassing global dynamic events underlying various brain-related disorders
ranging from neuropsychiatric disorders, degenerative disorders, mental illness,
and most importantly brain-specific neurotrauma-related injuries. In this
introductory chapter, we will provide a brief historical perspective on the field
of neuroproteomics. In doing so, we will highlight on the recent applications of
neuroproteomics in the areas of neurotrauma, an area that has benefitted from
neuroproteomics in terms of biomarker research, spatiotemporal injury mechanism,
and its use to translate its findings from experimental settings to human
translational applications. Importantly, this chapter will include some
recommendation to the general studies in the area of neuroproteomics and the need
to move from this field from being a descriptive, hypothesis-free approach to
being an independent mature scientific discipline.
PMID- 28508357
TI - Biofluid Proteomics and Biomarkers in Traumatic Brain Injury.
AB - Traumatic brain injury (TBI) is an injury to the brain caused by an external
mechanical force, affecting millions of people worldwide. The disease course and
prognosis are often unpredictable, and it can be challenging to determine an
early diagnosis in case of mild injury as well as to accurately phenotype the
injury. There is currently no cure for TBI-drugs having failed repeatedly in
clinical trials-but an intense effort has been put to identify effective
neuroprotective treatment. The detection of novel biomarkers, to understand more
of the disease mechanism, facilitates early diagnosis, predicts disease
progression, and develops molecularly targeted therapies that would be of high
clinical interest. Over the last decade, there has been an increasing effort and
initiative toward finding TBI-specific biomarker candidates. One promising
strategy has been to use state-of-the-art neuroproteomics approaches to assess
clinical biofluids and compare the cerebrospinal fluid (CSF) and blood proteome
between TBI and control patients or between different subgroups of TBI. In this
chapter, we summarize and discuss the status of biofluid proteomics in TBI, with
a particular focus on the latest findings.
PMID- 28508356
TI - Progress and Potential of Imaging Mass Spectrometry Applied to Biomarker
Discovery.
AB - Mapping provides a direct means to assess the impact of protein biomarkers and
puts into context their relevance in the type of cancer being examined. To this
end, mass spectrometry imaging (MSI) was developed to provide the needed spatial
information which is missing in traditional liquid-based mass spectrometric
proteomics approaches. Aptly described as a "molecular histology" technique, MSI
gives an additional dimension in characterizing tumor biopsies, allowing for
mapping of hundreds of molecules in a single analysis. A decade of developments
focused on improving and standardizing MSI so that the technique can be
translated into the clinical setting. This review describes the progress made in
addressing the technological development that allows to bridge local protein
detection by MSI to its identification and to illustrate its potential in
studying various aspects of cancer biomarker discovery.
PMID- 28508358
TI - Degradomics in Neurotrauma: Profiling Traumatic Brain Injury.
AB - Degradomics has recently emerged as a subdiscipline in the omics era with a focus
on characterizing signature breakdown products implicated in various disease
processes. Driven by promising experimental findings in cancer, neuroscience, and
metabolomic disorders, degradomics has significantly promoted the notion of
disease-specific "degradome." A degradome arises from the activation of several
proteases that target specific substrates and generate signature protein
fragments. Several proteases such as calpains, caspases, cathepsins, and matrix
metalloproteinases (MMPs) are involved in the pathogenesis of numerous diseases
that disturb the physiologic balance between protein synthesis and protein
degradation. While regulated proteolytic activities are needed for development,
growth, and regeneration, uncontrolled proteolysis initiated under pathological
conditions ultimately culminates into apoptotic and necrotic processes. In this
chapter, we aim to review the protease-substrate repertoires in neural injury
concentrating on traumatic brain injury. A striking diversity of protease
substrates, essential for neuronal and brain structural and functional integrity,
namely, encryptic biomarker neoproteins, have been characterized in brain injury.
These include cytoskeletal proteins, transcription factors, cell cycle regulatory
proteins, synaptic proteins, and cell junction proteins. As these substrates are
subject to proteolytic fragmentation, they are ceaselessly exposed to activated
proteases. Characterization of these molecules allows for a surge of "possible"
therapeutic approaches of intervention at various levels of the proteolytic
cascade.
PMID- 28508359
TI - Evolving Relevance of Neuroproteomics in Alzheimer's Disease.
AB - Substantial progress in the understanding of the biology of Alzheimer's disease
(AD) has been achieved over the past decades. The early detection and diagnosis
of AD and other age-related neurodegenerative diseases, however, remain a
challenging scientific frontier. Therefore, the comprehensive discovery (relating
to all individual, converging or diverging biochemical disease mechanisms),
development, validation, and qualification of standardized biological markers
with diagnostic and prognostic functions with a precise performance profile
regarding specificity, sensitivity, and positive and negative predictive value
are warranted.Methodological innovations in the area of exploratory high
throughput technologies, such as sequencing, microarrays, and mass spectrometry
based analyses of proteins/peptides, have led to the generation of large global
molecular datasets from a multiplicity of biological systems, such as biological
fluids, cells, tissues, and organs. Such methodological progress has shifted the
attention to the execution of hypothesis-independent comprehensive exploratory
analyses (opposed to the classical hypothesis-driven candidate approach), with
the aim of fully understanding the biological systems in physiology and disease
as a whole. The systems biology paradigm integrates experimental biology with
accurate and rigorous computational modelling to describe and foresee the dynamic
features of biological systems. The use of dynamically evolving technological
platforms, including mass spectrometry, in the area of proteomics has enabled to
rush the process of biomarker discovery and validation for refining significantly
the diagnosis of AD. Currently, proteomics-which is part of the systems biology
paradigm-is designated as one of the dominant matured sciences needed for the
effective exploratory discovery of prospective biomarker candidates expected to
play an effective role in aiding the early detection, diagnosis, prognosis, and
therapy development in AD.
PMID- 28508360
TI - Genome to Phenome: A Systems Biology Approach to PTSD Using an Animal Model.
AB - Post-traumatic stress disorder (PTSD) is a debilitating illness that imposes
significant emotional and financial burdens on military families. The
understanding of PTSD etiology remains elusive; nonetheless, it is clear that
PTSD is manifested by a cluster of symptoms including hyperarousal,
reexperiencing of traumatic events, and avoidance of trauma reminders. With these
characteristics in mind, several rodent models have been developed eliciting PTSD
like features. Animal models with social dimensions are of particular interest,
since the social context plays a major role in the development and manifestation
of PTSD.For civilians, a core trauma that elicits PTSD might be characterized by
a singular life-threatening event such as a car accident. In contrast, among war
veterans, PTSD might be triggered by repeated threats and a cumulative
psychological burden that coalesced in the combat zone. In capturing this
fundamental difference, the aggressor-exposed social stress (Agg-E SS) model
imposes highly threatening conspecific trauma on naive mice repeatedly and
randomly.There is abundant evidence that suggests the potential role of genetic
contributions to risk factors for PTSD. Specific observations include putatively
heritable attributes of the disorder, the cited cases of atypical brain
morphology, and the observed neuroendocrine shifts away from normative. Taken
together, these features underscore the importance of multi-omics investigations
to develop a comprehensive picture. More daunting will be the task of downstream
analysis with integration of these heterogeneous genotypic and phenotypic data
types to deliver putative clinical biomarkers. Researchers are advocating for a
systems biology approach, which has demonstrated an increasingly robust potential
for integrating multidisciplinary data. By applying a systems biology approach
here, we have connected the tissue-specific molecular perturbations to the
behaviors displayed by mice subjected to Agg-E SS. A molecular pattern that links
the atypical fear plasticity to energy deficiency was thereby identified to be
causally associated with many behavioral shifts and transformations.PTSD is a
multifactorial illness sensitive to environmental influence. Accordingly, it is
essential to employ the optimal animal model approximating the environmental
condition that elicits PTSD-like symptoms. Integration of an optimal animal model
with a systems biology approach can contribute to a more knowledge-driven and
efficient next-generation care management system and, potentially, prevention of
PTSD.
PMID- 28508361
TI - Photoaffinity Labeling of Pentameric Ligand-Gated Ion Channels: A Proteomic
Approach to Identify Allosteric Modulator Binding Sites.
AB - Photoaffinity labeling techniques have been used for decades to identify drug
binding sites and to study the structural biology of allosteric transitions in
transmembrane proteins including pentameric ligand-gated ion channels (pLGIC). In
a typical photoaffinity labeling experiment, to identify drug binding sites, UV
light is used to introduce a covalent bond between a photoreactive ligand (which
upon irradiation at the appropriate wavelength converts to a reactive
intermediate) and amino acid residues that lie within its binding site. Then
protein chemistry and peptide microsequencing techniques are used to identify
these amino acids within the protein primary sequence. These amino acid residues
are located within homology models of the receptor to identify the binding site
of the photoreactive probe. Molecular modeling techniques are then used to model
the binding of the photoreactive probe within the binding site using docking
protocols. Photoaffinity labeling directly identifies amino acids that contribute
to drug binding sites regardless of their location within the protein structure
and distinguishes them from amino acids that are only involved in the
transduction of the conformational changes mediated by the drug, but may not be
part of its binding site (such as those identified by mutational studies). Major
limitations of photoaffinity labeling include the availability of photoreactive
ligands that faithfully mimic the properties of the parent molecule and protein
preparations that supply large enough quantities suitable for photoaffinity
labeling experiments. When the ligand of interest is not intrinsically
photoreactive, chemical modifications to add a photoreactive group to the parent
drug, and pharmacological evaluation of these chemical modifications become
necessary. With few exceptions, expression and affinity-purification of proteins
are required prior to photolabeling. Methods to isolate milligram quantities of
highly enriched pLGIC suitable for photoaffinity labeling experiments have been
developed. In this chapter, we discuss practical aspects of experimental
strategies to identify allosteric modulator binding sites in pLGIC using
photoaffinity labeling.
PMID- 28508362
TI - Quantitative Phosphoproteomic Analysis of Brain Tissues.
AB - Protein phosphorylation regulates brain development and neuronal activities; and
dysregulation of phosphorylation contributes to neurobiological disorders.
Phosphoproteomic analysis provides comprehensive modification maps for measuring
protein activities in cellular pathways and biological processes. Here, we
introduce a mass spectrometry (MS)-based protocol to quantitatively analyze the
phosphoproteome of human postmortem brains of Alzheimer's disease. In this
isobaric labeling protocol, up to ten brain samples are selected from control and
diseased cases for comparison. Approximately 1 mg proteins per sample are
extracted, digested, labeled, and then mixed at an equal ratio. To improve the
coverage of phosphoproteome, the peptide mix is further fractionated by offline
basic pH reversed-phase liquid chromatography (LC) with high-resolution power.
Phosphopeptides in each fraction are then enriched by the titanium dioxide method
and analyzed by online acidic pH reverse phase LC-MS/MS, leading to the analysis
of tens of thousands of phosphorylation events. This protocol can also be adapted
to profile phosphoproteome in other biological samples.
PMID- 28508364
TI - A Novel 2-DE-Based Proteomic Analysis to Identify Multiple Substrates for
Specific Protease in Neuronal Cells.
AB - Proteolysis is a process where proteins are broken down into smaller polypeptides
or amino acids, comprising one of the important posttranslational modifications
of proteins. Since this process is exquisitely achieved by specialized enzymes
called proteases under physiological conditions, abnormal protease activity and
dysregulation of their substrate proteins are closely associated with a
progression of several neurodegenerative diseases including Alzheimer disease,
Parkinson disease, stroke, and spinal cord injury. Thus, it is important to
identify the specific substrates of proteases with nonbiased high-throughput
screenings to understand how proteolysis contributes to neurodegeneration. Here,
we described a so-called gel-based protease proteomic approach. Critical steps of
our novel strategy consist of two-dimensional polyacrylamide gel electrophoresis
(2-DE)-based protein separation and in vitro incubation with the specific
protease of interest. As a prototypic example, cellular lysates obtained from
neuronal cells are separated by an isoelectric focusing, and the resulting
immobilized proteins on a gel strip are incubated with a predetermined amount of
a recombinant or a purified protease. By densitometric analysis of the Coomassie
Brilliant Blue-stained gel images following separation by 2-DE, significantly
altered protein spots are subjected to a mass spectral analysis for protein
identification. Interestingly, the concepts of our strategy can be applied to any
proteases, and to any neural cells or neural tissues of one's interest. Since the
immobilized protein spots are exposed to the purified protease, this protocol
ensures the identification of only substrates that are directly cleaved by
specific protease. This protocol ensures to avoid the possibility of identifying
substrates that may be cleaved by combinatorial or sequential activation of
proteolytic enzymes present in a liquid state of the lysates. We propose that our
strategy can be effectively utilized to provide meaningful insights into newly
identified protease substrates and to decipher molecular mechanisms critically
involved in neurodegenerative processes.
PMID- 28508363
TI - Glycoproteins Enrichment and LC-MS/MS Glycoproteomics in Central Nervous System
Applications.
AB - Proteins and glycoproteins play important biological roles in central nervous
systems (CNS). Qualitative and quantitative evaluation of proteins and
glycoproteins expression in CNS is critical to reveal the inherent biomolecular
mechanism of CNS diseases. This chapter describes proteomic and glycoproteomic
approaches based on liquid chromatography/tandem mass spectrometry (LC-MS or LC
MS/MS) for the qualitative and quantitative assessment of proteins and
glycoproteins expressed in CNS. Proteins and glycoproteins, extracted by a mass
spectrometry friendly surfactant from CNS samples, were subjected to enzymatic
(tryptic) digestion and three down-stream analyses: (1) a nano LC system coupled
with a high-resolution MS instrument to achieve qualitative proteomic profile,
(2) a nano LC system combined with a triple quadrupole MS to quantify identified
proteins, and (3) glycoprotein enrichment prior to LC-MS/MS analysis. Enrichment
techniques can be applied to improve coverage of low abundant
glycopeptides/glycoproteins. An example described in this chapter is hydrophilic
interaction liquid chromatographic (HILIC) enrichment to capture glycopeptides,
allowing efficient removal of peptides. The combination of three LC-MS/MS-based
approaches is capable of the investigation of large-scale proteins and
glycoproteins from CNS with an in-depth coverage, thus offering a full view of
proteins and glycoproteins changes in CNS.
PMID- 28508365
TI - Neuroproteomic Profiling of Cerebrospinal Fluid (CSF) by Multiplexed Affinity
Arrays.
AB - Protein profiling through affinity proteomic approaches represents a powerful
strategy for the analysis of human body fluids. Cerebrospinal fluid (CSF), being
the fluid proximal to the central nervous system, is commonly analyzed in the
context of neurological diseases, and can offer novel insights into the
physiological state of the brain. Ultimately, and by analyzing the presence of
brain-derived proteins in larger sets of samples that represent different
phenotypes, profiling of CSF may serve as an important source to discover and
verify disease-associated markers. Here, we describe a multiplexed and flexible
protein profiling approach using antibody-based assays on suspension bead arrays.
Through streamlined sample processing, protein biotinylation, and single-binder
assay readout, this method enables high-throughput neuroproteomic analysis of up
to 384 proteins in 384 samples.
PMID- 28508366
TI - Isolation and Proteomic Analysis of Microvesicles and Exosomes from HT22 Cells
and Primary Neurons.
AB - Exosomes and microvesicles are extracellular vesicles (EVs) released by most cell
types. The role of EVs as a method of intercellular communication has led to
these vesicles becoming a major area of interest in a variety of scientific
fields including neuroscience. Emerging evidence is now demonstrating that the
biomolecular composition of EVs, especially exosomes, can play a role in the
progression of disease including various neurodegenerative diseases and cancer.
In addition to the miRNA profiles of EVs, these vesicles also show interesting
changes in protein expression profiles under different physiological and
pathological conditions. Characterization of these profiles could prove valuable
for both understanding disease pathogenesis and for the discovery of new
biomarkers of disease. In this chapter, we describe a protocol for isolation of
exosomes and microvesicles from immortalized HT22 cells and primary cortical
neurons with sufficient yield and low serum contamination required for downstream
analysis and label-free relative quantitation by mass spectrometry.
PMID- 28508367
TI - Combined MALDI Mass Spectrometry Imaging and Parafilm-Assisted Microdissection
Based LC-MS/MS Workflows in the Study of the Brain.
AB - Proteins and other biomolecules such as lipids are significant players in the
central nervous system and are implicated in various neurological disorders.
Their identification, quantification, and distribution are thus important not
only in understanding the disease but also in developing treatments. A combined
workflow allowing the localized microextraction of discrete regions identified by
a matrix-assisted laser desorption/ionization mass spectrometry (MSI) imaging
experiment for proteomics analysis by liquid chromatography/tandem mass
spectrometry (LC MS/MS) is described in this chapter. MSI was initially used to
map lipid distributions allowing for the identification of regions of interest
(ROIs) that are then subjected to microextraction in a consecutive tissue
section. Mounting of consecutive tissue on parafilm allows microdissection of the
ROIs, where proteins can then be recovered for processing and LC MS/MS analysis.
The PAM method provides a fast and cheap means to perform further downstream
analysis after an MSI experiment.
PMID- 28508368
TI - De Novo and Uninterrupted SILAC Labeling of Primary Microglia.
AB - Microglia have increasingly been recognized as playing a wide spectrum of roles
in various physiological and pathological processes in the central nervous
system. Studies in the past have mostly associated individual microglial enzymes
or soluble factors such as cytokines with specific functions of microglia. Stable
isotope labeling with amino acids in cell culture (SILAC)-based proteomic
analysis enables an unbiased, simultaneous, and global-scale analysis of the
expression of thousands of proteins involved in key cellular pathways that
regulate microglial activities. Primary microglia, characteristically, bear a
much greater resemblance to microglia in vivo than immortalized microglial cell
lines. In this chapter, we provide a detailed protocol for a de novo and
uninterrupted primary culture SILAC labeling strategy (DUP-SILAC) for primary rat
microglia that could be applied to the analysis of microglial involvement in
various normal and disease processes.
PMID- 28508369
TI - Spike-In SILAC Approach for Proteomic Analysis of Ex Vivo Microglia.
AB - Stable isotope labeling by amino acids in cell culture (SILAC) is a versatile
mass spectrometry-based proteomic approach that can achieve accurate relative
protein quantitation on a global scale. In this approach, proteins are labeled
while being synthesized by the cell due to the presence of certain amino acids
exclusively as heavier mass analogs than their regular (light) counterparts. This
differential labeling allows for the identification of heavy and light forms of
each peptide corresponding to two or more different experimental groups upon mass
spectrometric analysis, the intensities of which reflect their abundance in the
sample analyzed. Relative quantitation is straightforward when SILAC labeling
efficiency is high (>99%) and the same cell proteome is used as the quantitation
reference, which is typically the case for immortalized cell lines. However, the
SILAC methodology for the proteomic analysis of primary cells isolated after in
vivo experimentation is more challenging given the low labeling efficiency that
would be achieved post-isolation. Alternatively, a stable-isotope-labeled cell
line representing the cell type can be used as an internal standard (spike-in
SILAC); however, adequate representation of the primary cell proteome with the
stable-isotope-labeled internal standard may limit overall protein quantitation,
especially for cell types that exhibit a broad range of phenotypes such as
microglia, the resident immune cells in the brain. Here, we present a way to
circumvent this limitation by combining multiple phenotypes of a single-cell type
(the immortalized mouse BV2 microglial cell line) into a single spike-in standard
using primary mouse microglia as our model system. We describe the preparation of
media, incorporation of labels, induction of four different activation states
(plus resting), isolation of primary microglia from adult mice brains,
preparation of lysates for analysis, and general guidelines for data processing.
PMID- 28508370
TI - A Proteomic Evaluation of Sympathetic Activity Biomarkers of the Hypothalamus
Pituitary-Adrenal Axis by Western Blotting Technique Following Experimental
Traumatic Brain Injury.
AB - Endocrine disorders and autonomic dysfunction are common paradigms following
traumatic brain injury (TBI). Alterations in the hypothalamus-pituitary-adrenal
(HPA) axis following TBI may result in impaired vasopressor response, energy
imbalance, fatigue, depression, or neurological disorders. Autonomic dysfunction
is a common disorder following TBI. The sympathetic activity markers on HPA axis
can be measured by Western blot protein analysis. Tyrosine hydroxylase, dopamine
beta hydroxylase are the key enzymes for the synthesis of norepinephrine; and
neuropeptide Y (NPY) is the peptide that is co-stored and co-released with
norepinephrine. Thus, the present chapter reviews the experimental protocols for
Western blot protein analysis for the measurement of biomarkers that indicate
sympathetic activity in brain regions (hypothalamus, pituitary, cerebral cortex,
and cerebellum) following TBI.
PMID- 28508371
TI - Efficient and Accurate Algorithm for Cleaved Fragments Prediction (CFPA) in
Protein Sequences Dataset Based on Consensus and Its Variants: A Novel
Degradomics Prediction Application.
AB - Degradomics is a novel discipline that involves determination of the
proteases/substrate fragmentation profile, called the substrate degradome, and
has been recently applied in different disciplines. A major application of
degradomics is its utility in the field of biomarkers where the breakdown
products (BDPs) of different protease have been investigated. Among the major
proteases assessed, calpain and caspase proteases have been associated with the
execution phases of the pro-apoptotic and pro-necrotic cell death, generating
caspase/calpain-specific cleaved fragments. The distinction between calpain and
caspase protein fragments has been applied to distinguish injury mechanisms.
Advanced proteomics technology has been used to identify these BDPs
experimentally. However, it has been a challenge to identify these BDPs with high
precision and efficiency, especially if we are targeting a number of proteins at
one time. In this chapter, we present a novel bioinfromatic detection method that
identifies BDPs accurately and efficiently with validation against experimental
data. This method aims at predicting the consensus sequence occurrences and their
variants in a large set of experimentally detected protein sequences based on
state-of-the-art sequence matching and alignment algorithms. After detection, the
method generates all the potential cleaved fragments by a specific protease. This
space and time-efficient algorithm is flexible to handle the different
orientations that the consensus sequence and the protein sequence can take before
cleaving. It is O(mn) in space complexity and O(Nmn) in time complexity, with N
number of protein sequences, m length of the consensus sequence, and n length of
each protein sequence. Ultimately, this knowledge will subsequently feed into the
development of a novel tool for researchers to detect diverse types of selected
BDPs as putative disease markers, contributing to the diagnosis and treatment of
related disorders.
PMID- 28508372
TI - Effect of Second-Hand Tobacco Smoke on the Nitration of Brain Proteins: A Systems
Biology and Bioinformatics Approach.
AB - Second-hand smoke (SHS) exposure leads to the death of approximately 48,000
nonsmokers per year in the United States alone. SHS exposure has been associated
with cardiovascular, respiratory, and neurodegenerative diseases. While cardiac
function abnormalities and lung cancer due to SHS have been well characterized,
brain injury due to SHS has not undergone a full systematic evaluation. Oxidative
stress and nitration have been associated with smoking and SHS exposure. Animal
studies suggest that exposure to tobacco smoke increases oxidative stress.
Oxidative stress is characterized by an increase in reactive oxygen and nitrogen
species (ROS/RNS). Among the oxidative mechanisms affecting protein functionality
is the posttranslational modification (PTM)-mediated tyrosine nitration. Protein
tyrosine nitration, a covalent posttranslational modification, is commonly used
as a marker of cellular oxidative stress associated with the pathogenesis of
several neurodegenerative diseases. In our previous published work, the utility
of a targeted proteomic approach has been evaluated to identify two brain
abundant proteins in an in vivo SHS rat model namely the GAPDH and UCH-L1. In
this current study, mass spectrometric-based proteomic and complementary
biochemical methods were used to characterize the SHS-induced brain nitroproteome
followed by bioinformatics/systems biology approach analysis to characterize
protein interaction map. Sprague Dawley rats were exposed to SHS for 5 weeks and
then cortical tissues were collected. Nitroprotein enrichment was performed via 3
Nitro tyrosine (3-NT) immunoprecipitation of brain lysates proteins. Protein
nitration was validated via Western blotting to confirm the presence of
nitroproteins complemented by gel-free neuroproteomic analysis by data-dependent
LC-MS/MS. We identified 29 differentially expressed proteins in the 3-NT-enriched
samples; seven of these proteins were unique to SHS exposure. Network analysis
revealed an association of the proteins to different cellular processes including
oxidative stress, ROS generation, and cell death-related pathway. This confirms
the association of oxidative stress mechanisms with SHS which may contribute to
neuronal injury, an area that has not been well studied in the area smoking.
PMID- 28508373
TI - An Advanced Omic Approach to Identify Co-Regulated Clusters and Transcription
Regulation Network with AGCT and SHOE Methods.
AB - To obtain the global picture of genetic machinery for massive high-throughput
gene expression data, novel data-driven unsupervised learning approaches are
becoming essentially important. For this purpose, basic analytic workflow has
been established and should include two steps: first, unsupervised clustering to
identify genes with similar behavior upon exposure to a signal, and second,
identification of transcription factors regulating those genes. In this chapter,
we will describe an advanced tool that can be used for analyzing and
characterizing large-scale time-series gene expression composed of a two-step
approach. For the first step, we developed an original method "A Geometric
Clustering Tool" (AGCT) that unveils the complex architecture of large-scale time
series gene expression data in a real-time manner using cutting edge techniques
of low dimension manifold learning, data clustering, and visualization. For the
second step, we established an original method "Sequence Homology in Eukaryotes"
(SHOE) executing comparative genomic analysis on humans, mice, and rats.
PMID- 28508374
TI - AutoDock and AutoDockTools for Protein-Ligand Docking: Beta-Site Amyloid
Precursor Protein Cleaving Enzyme 1(BACE1) as a Case Study.
AB - Computational docking and scoring techniques have revolutionized structural
bioinformatics by providing unprecedented insights on key aspects of ligand
receptor interaction. Docking is used for optimizing known drugs and for
identifying novel binders by predicting their binding mode and affinity. AutoDock
and AutoDockTools are free of charge techniques that have been extensively cited
in the literature as essential tools in structure-based drug design. Moreover,
these methods are fast enough to permit virtual screening of ligand libraries
containing tens of thousands of compounds. However using Autodock requires some
knowledge in programming which creates a limitation for biologists and makes them
prone for commercial applications. Here, we selected a relevant target involved
in the progression of Alzheimer disease and provided a fully reproducible docking
protocol. This example will show how docking techniques would be an important
asset to identify new BACE1 inhibitors. The following friendly user tutorial
targets both undergraduate and graduate students, allowing them to understand
docking as a computational tool for structure-based drug design.
PMID- 28508375
TI - An Integration of Decision Tree and Visual Analysis to Analyze Intracranial
Pressure.
AB - In Traumatic Brain Injury (TBI), elevated Intracranial Pressure (ICP) causes
severe brain damages due to hemorrhage and swelling. Monitoring ICP plays an
important role in the treatment of TBI patients because ICP is considered a
strong predictor of neurological outcome and a potentially amenable method to
treat patients. However, it is difficult to predict and measure accurate ICP due
to the complex nature of patients' clinical conditions. ICP monitoring for severe
TBI patient is a challenging problem for clinicians because traditionally known
ICP monitoring is an invasive procedure by placing a device inside the brain to
measure pressure. Therefore, ICP monitoring might have a high infection risk and
cause medical complications. In here, an ICP monitoring using texture features is
proposed to overcome this limitation. The combination of image processing methods
and a decision tree algorithm is utilized to estimate ICP of TBI patients
noninvasively. In addition, a visual analytics tool is used to conduct an
interactive visual factor analysis and outlier detection.
PMID- 28508377
TI - Emulsion versus nanoemulsion: how much is the formulative shift critical for a
cosmetic product?
AB - The use of nanoemulsions in cosmetic products has been enlarged in the last
decades because of several formulative advantages (e.g., the improved self-life
stability, better texture properties). In addition, nanoemulsions seemed to
improve the penetration of active ingredients through the human skin, comparing
to conventional emulsion. In this contest, the risk of a higher systemic exposure
of consumer to active ingredients, due to the ability of nanoemulsion to enhance
permeation, results a critical attribute that should be evaluated for assuring
the consumer safety. The aim of this work was the evaluation of how an oil-in
water (O/W) nanoemulsion can influence the in vitro skin permeation profiles of
two model active ingredients with different polarity (i.e., caffeine and ethyl
ximenynate). Preliminarily, since both selected molecules influenced the physical
stability of nanoemulsion, formulative studies were carried out to identify the
most stable formulation to perform in vitro permeation studies. The overall
results demonstrated that nanoemulsions could significantly influence the
permeation profiles of molecules as a function of their physicochemical
properties. In particular, O/W nanoemulsions significantly improved the
permeation profiles of apolar active ingredients in comparison to conventional
emulsions, whereas no differences were observable for polar molecules.
Considering such findings, it is worth observing that there is room for
reconsidering the risk assessment of nanoemulsion-based cosmetic products.
PMID- 28508378
TI - Population Pharmacokinetic and Pharmacodynamic Modeling of Etelcalcetide in
Patients with Chronic Kidney Disease and Secondary Hyperparathyroidism Receiving
Hemodialysis.
AB - INTRODUCTION: Etelcalcetide is a novel calcimimetic that binds and activates
calcium-sensing receptors (CaSRs) for the treatment of secondary
hyperparathyroidism (SHPT). METHODS: To assess titrated dosing regimens,
population pharmacokinetic (PK) and PK/pharmacodynamic (PKPD) modeling of
etelcalcetide was performed using NONMEM 7.2. In this analysis, plasma
etelcalcetide, serum parathyroid hormone (PTH) and calcium (Ca) concentration
time data were collected from five phase I, II, and III clinical trials following
single or multiple intravenous doses of etelcalcetide ranging from 2.5 to 60 mg.
A semi-mechanistic model was used to describe the relationship between
etelcalcetide, PTH, and Ca. This model included the role of PTH in Ca regulation,
the feedback of Ca onto PTH production via the CaSR, and the activity of
etelcalcetide plasma levels in increasing the sensitivity of the CaSR to Ca via
the cooperative binding model. The impact of relevant covariates was evaluated by
stepwise forward/backward selection. Model evaluation was based on standard
goodness-of-fit plots and prediction-corrected visual predictive checks (pcVPCs).
Simulation was conducted to evaluate titrated dosing regimens. RESULTS AND
DISCUSSION: The time courses of etelcalcetide, PTH, and Ca were well-described by
the model. The clearance and central volume of distribution (Vc) of etelcalcetide
were 0.472 L/h and 49.9 L, respectively, while estimates of the turnover half
lives of PTH and Ca were 0.36 and 23 h, respectively. The extent of
interindividual variability in model parameters was low to moderate (6-67%), and
no covariates were identified as significant predictors of PK and PD variability.
pcVPCs confirmed the predictive ability of the model. CONCLUSIONS: The current
analysis confirms the putative mechanism of action of etelcalcetide as an
allosteric activator of CaSR. Simulations showed that dose titration of
etelcalcetide, rather than fixed dose, is needed to effectively decrease the PTH
level in patient populations.
PMID- 28508376
TI - In vivo and qualitative studies investigating the translational potential of
microneedles for use in the older population.
AB - Microneedles (MNs) are a novel transdermal drug delivery platform, rapidly
progressing from a substantive evidence base, towards commercialisation. As part
of this transition, it is important to consider the future use of MNs by older
people in order to ensure optimal therapeutic outcomes for this unique and
increasing population group. This paper, therefore, considers the use of MNs by
those aged over 65 years, investigating insertion parameters in ageing skin,
alongside the feasibility and acceptability of the technology. Hydrogel-forming
MN arrays were applied to seven subjects aged over 65 years, with breach of the
stratum corneum confirmed using optical coherence tomography. Insertion depths
recorded in each case were similar to a comparative group, aged 20-30 years. Skin
recovery was, however, demonstrated to occur at a slower rate in the older
subjects, as measured using transepidermal water loss. Qualitative methods,
including focus groups and semi-structured interviews, were employed to collect
the views and opinions of older people and community pharmacists respectively.
The overall consensus was positive, with a number of benefits to MN-mediated drug
delivery identified, such as reduced dosing frequency, improved adherence and an
alternative delivery route where oral or injectable medication was precluded.
Concerns centred on practical issues associated with age-related functional
decline, including, for example, reduced dexterity and skin changes. The
presentation of this work collectively provides the first convincing report of
the importance of further translational research in this area to support future
MN use in older people, ensuring an age-appropriate delivery platform.
PMID- 28508379
TI - [Retinal pigment epithelial detachment in hyperviscosity syndrome].
AB - We present a case of a 57-year-old woman who reported bilateral visual impairment
since 2 weeks. She had a medical history of congenital, cyanotic heart failure.
Funduscopic examination revealed serous retinal detachment on the left side,
central subneurosensory detachment on the right side, retinal vessel tortuosity
and multiple retinal haemorrhages in the periphery. As blood analysis showed a
distinct increase in haemoglobin and haematocrit, hyperviscosity syndrome was
suspected to have caused bilateral serous retinal detachment. Isovolemic
haemodilution was performed in close cooperation with the cardiology department
with repeated phlebotomy, which resulted in a significant reduction of subretinal
fluid and, concurrently, an increase in visual acuity.
PMID- 28508380
TI - [Optical coherence tomography in eyes with senile retinoschisis : SD-OCT versus
ultrasound examinations and assessment of the vitreoretinal interface].
AB - BACKGROUND: In addition to ocular ultrasonography (US), spectral domain optical
coherence tomography (SD-OCT) is available in order to diagnose senile
retinoschisis (sRS). SD-OCT also allows for classification of posterior vitreous
detachment (PVD) in healthy eyes. OBJECTIVES: Reevaluation of the value and
additional benefit of both imaging procedures. SD-OCT-based evaluation of PVD
stages in sRS patients. MATERIALS AND METHODS: Diagnostic results of 33 eyes in
26 patients with clinical suspicion of sRS were retrospectively analysed. All
patients received a SD-OCT and a 10 MHz US examination of the region of interest
(RoI). In 32 eyes the PVD stage was classified by SD-OCT using the description by
Uchino et al. The vitreous position in peripheral SD-OCT scans with sRS was
reviewed. RESULTS: SD-OCT confirmed sRS in 29 eyes. US examination identified sRS
in 26 eyes. In 11 eyes, the examination results of the two methods differed. In 7
eyes sRS was identified by SD-OCT but not by US examination. US examination
confirmed sRS in 4 eyes for which SD-OCT scans were not useful. Most cases of sRS
were detected in temporal located retinal lesions. There was no significant
difference between the results of both imaging procedures regarding the RoI (p =
0.64). SD-OCT provided additional information in 27 eyes. Four eyes did not
present PVD. Early and intermediate stages of PVD were detected in 9 eyes, while
19 eyes showed complete PVD. In most cases, the vitreous could not be identified
in the SD-OCT scans of the periphery. CONCLUSIONS: In clinical practice, neither
SD-OCT nor US ensure an explicit finding of sRS in each eye with sRS. However,
both methods positively complement one another and together they improve image
based diagnosis. All stages of PVD may be found in eyes with sRS. The
contribution of the vitreous to the pathogenesis of sRS remains uncertain.
PMID- 28508382
TI - Think fast: rapid assessment of the effects of episodic future thinking on delay
discounting in overweight/obese participants.
AB - Accumulating laboratory-based evidence indicates that reducing delay discounting
(devaluation of delayed outcomes) with the use of episodic future thinking (EFT;
mental simulation of future events) improves dietary decision-making and other
maladaptive behaviors. Recent work has adapted EFT for use in the natural
environment to aid in dietary and weight control by engaging participants in EFT
repeatedly throughout the day. These efforts may benefit from minimizing the
amount of time required for measurement and implementation of EFT. Using Amazon
Mechanical Turk in the present study, we show that EFT effectively reduces delay
discounting in overweight/obese participants (N = 131) using the recently
developed 5-trial, adjusting-delay discounting task, which can be completed
rapidly (25 s) and is therefore ideally suited for ecological momentary
assessment. Moreover, measures of delay discounting from this task were strongly
correlated with those from the commonly used adjusting-amount task (r = .859).
Significant effects of EFT on discounting, however, depended on the number of
future events participants generated and imagined. Use of a range of events and
future time frames (as is typical in the literature) significantly reduced delay
discounting, whereas use of only a single event did not.
PMID- 28508381
TI - Visualization of metallodrugs in single cells by secondary ion mass spectrometry
imaging.
AB - Secondary ion mass spectrometry, including nanoscale secondary ion mass
spectrometry (NanoSIMS) and time-of-flight secondary ion mass spectrometry (ToF
SIMS), has emerged as a powerful tool for biological imaging, especially for
single cell imaging. SIMS imaging can provide information on subcellular
distribution of endogenous and exogenous chemicals, including metallodrugs, from
membrane through to cytoplasm and nucleus without labeling, and with high spatial
resolution and chemical specificity. In this mini-review, we summarize recent
progress in the field of SIMS imaging, particularly in the characterization of
the subcellular distribution of metallodrugs. We anticipate that the SIMS imaging
method will be widely applied to visualize subcellular distributions of drugs and
drug candidates in single cells, exerting significant influence on early drug
evaluation and metabolism in medicinal and pharmaceutical chemistry. Recent
progress of SIMS applications in characterizing the subcellular distributions of
metallodrugs was summarized.
PMID- 28508385
TI - Improving the temperature characteristics and catalytic efficiency of a
mesophilic xylanase from Aspergillus oryzae, AoXyn11A, by iterative mutagenesis
based on in silico design.
AB - To improve the temperature characteristics and catalytic efficiency of a
glycoside hydrolase family (GHF) 11 xylanase from Aspergillus oryzae (AoXyn11A),
its variants were predicted based on in silico design. Firstly, Gly21 with the
maximum B-factor value, which was confirmed by molecular dynamics (MD) simulation
on the three-dimensional structure of AoXyn11A, was subjected to site-saturation
mutagenesis. Thus, one variant with the highest thermostability, AoXyn11AG21I,
was selected from the mutagenesis library, E. coli/Aoxyn11A G21X (X: any one of
20 amino acids). Secondly, based on the primary structure multiple alignment of
AoXyn11A with seven thermophilic GHF11 xylanases, AoXyn11AY13F or AoXyn11AG21I
Y13F, was designed by replacing Tyr13 in AoXyn11A or AoXyn11AG21I with Phe.
Finally, three variant-encoding genes, Aoxyn11A G21I, Aoxyn11A Y13F and Aoxyn11A
G21I-Y13F, were constructed by two-stage whole-plasmid PCR method, and expressed
in Pichia pastoris GS115, respectively. The temperature optimum (T opt) of
recombinant (re) AoXyn11AG21I-Y13F was 60 degrees C, being 5 degrees C higher
than that of reAoXyn11AG21I or reAoXyn11AY13F, and 10 degrees C higher than that
of reAoXyn11A. The thermal inactivation half-life (t 1/2) of reAoXyn11AG21I-Y13F
at 50 degrees C was 240 min, being 40-, 3.4- and 2.5-fold longer than those of
reAoXyn11A, reAoXyn11AG21I and reAoXyn11AY13F. The melting temperature (T m)
values of reAoXyn11A, reAoXyn11AG21I, reAoXyn11AY13F and reAoXyn11AG21I-Y13F were
52.3, 56.5, 58.6 and 61.3 degrees C, respectively. These findings indicated that
the iterative mutagenesis of both Gly21Ile and Tyr13Phe improved the temperature
characteristics of AoXyn11A in a synergistic mode. Besides those, the catalytic
efficiency (k cat/K m) of reAoXyn11AG21I-Y13F was 473.1 mL mg-1 s-1, which was
1.65-fold higher than that of reAoXyn11A.
PMID- 28508384
TI - Endoscopic Management of Benign Esophageal Ruptures and Leaks.
AB - OPINION STATEMENT: Esophageal leaks (EL) and ruptures (ER) are rare conditions
associated with a high risk of mortality and morbidity. Historically, EL and ER
have been surgically treated, but current treatment options also include
conservative management and endoscopy. Over the last decades, interventional
endoscopy has evolved as an effective and less invasive alternative to primary
surgery in these cases. A variety of techniques are currently available to re
establish the continuity of the digestive tract, prevent or treat infection
related to the leak/rupture, prevent further contamination, drain potential
collections, and provide nutritional support. Endoscopic options include clips,
both through the scope (TTS) and over the scope (OTS), stent placement, vacuum
therapy, tissue adhesive, and endoscopic suturing techniques. Theoretically, all
of these can be used alone or with a multimodality approach. Endoscopic therapy
should be combined with medical therapy but also with percutaneous drainage of
collections, where present. There is robust evidence suggesting that this change
of therapeutic paradigm in the form of endoscopic therapy is associated with
improved outcome, better quality of life, and shortened length of hospital stay.
Moreover, recent European guidelines on endoscopic management of iatrogenic
perforation have strengthened and to some degree regulated and redefined the role
of endoscopy in the management of conditions where there is a breach in the
continuity of the GI wall. Certainly, due to the complexity of these conditions
and the variety of available treatment options, a multidisciplinary approach is
strongly recommended, with close clinical monitoring (by endoscopists, surgeons,
and intensive care physicians) and special attention to signs of sepsis, which
can lead to the need for urgent surgical management. This review article will
critically discuss the literature regarding endoscopic modalities for esophageal
leak and perforation management and attempt to place them in perspective for the
physician.
PMID- 28508386
TI - Application of response surface methodology for optimization of medium components
for the production of secondary metabolites by Streptomyces diastatochromogenes
KX852460.
AB - A bioactive strain Streptomyces diastatochromogenes KX852460 was selected for the
production of secondary metabolites to control the target spot disease on tobacco
leaves, caused by the Rhizoctonia solani AG-3. Peanut meal, soluble starch, NaCl,
yeast extract, and ammonium sulphate were identified the best ingredient for high
antifungal activity of S. diastatochromogenes KX852460 against the R. solani AG
3. For the improved production of secondary metabolites, central composite design
of response surface methodology was applied in submerged fermentation. The best
concentrations of ingredients were peanut meal 4.88%, soluble starch 4.40%, NaCl
0.52%, yeast extract 0.47%, and ammonium sulphate 0.0360%. Study of metabolism
changes in the submerged fermentation process was analyzed. Level of the reducing
sugar increased, as the total sugar consumed. Amino nitrogen and total sugar
decrease tendency, which indicated the growth of bacteria in submerged
fermentation batch. Production of secondary and other metabolites influenced the
pH of the fermentation batch.
PMID- 28508387
TI - No evidence for induction of autoantibodies or autoimmunity during treatment of
psoriasis with ustekinumab.
PMID- 28508383
TI - Spiritual well-being, religious activity, and the metabolic syndrome: results
from the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary
Study.
AB - Sociocultural risk and protective factors for developing the metabolic syndrome
(MetS), a risk factor for cardiovascular disease (CVD), have not been well
studied in Hispanics/Latinos residing in the United States (U.S.). Religiosity
and/or spirituality (R/S), important aspects of Hispanic/Latino culture, have
been inversely associated with CVD and multiple CVD risk factors. Cross-sectional
associations between dimensions of R/S and prevalent MetS, and its five
individual components were examined using multiple logistic and linear
regression, among 3278 U.S., middle-aged and older Hispanic/Latino adults from
the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary
Study. Dimensions of R/S were not associated with presence of the MetS. Certain
dimensions of Spiritual Well-being (Meaning, Peace, Faith), and frequency of non
organizational religious activity were weakly but significantly associated with
one or more MetS components including waist circumference, diastolic blood
pressure, and systolic blood pressure. R/S variables were not associated with
triglycerides, fasting glucose or HDL cholesterol levels. Prospective,
longitudinal studies are needed to gain a deeper understanding of the nature of
the relationship between R/S and health risk factors in U.S. Hispanics/Latinos.
PMID- 28508388
TI - Positive clinical outcome in a patient with recalcitrant bullous pemphigoid
treated with rituximab and intravenous immunoglobulin.
AB - A 41-year-old white man was treated for bullous pemphigoid (BP) for 4 years,
using high-dose prednisone as well as ciclosporin and mycophenolate mofetil.
Sustained clinical improvement was not observed. He suffered several serious side
effects. Consequently, he was treated with a combination of rituximab (RTX) and
intravenous immunoglobulin (IVIg). He received 12 infusions of RTX in 6 months
and monthly IVIg until the end of the therapy. Within 5 weeks of this therapy,
appearance of new lesions ceased. Within 8 weeks, all previous lesions resolved
and previous medications were discontinued. No hospitalizations, relapses,
infections or other serious adverse events occurred. The high levels of
pathogenic autoantibody decreased and have remained undetectable. After three
infusions of RTX, CD19+ B cells were undetectable and returned to normal levels
within 18 months. The patient remains in complete clinical remission off all
systemic therapy and free of disease for a 20-month follow-up.
PMID- 28508389
TI - Usefulness of techniques based on real time PCR for the identification of
onychomycosis-causing species.
AB - Onychomycosis (OM) is a nail infection caused mainly by dermatophyte species but
other species of yeast and moulds are frequently involved as well. Classical
diagnosis has limitations thus empirical treatment is common. The usefulness of
different real time PCR (RT-PCR) assays for identifying species causing OM was
assessed in samples from seventy patients and fifteen controls. Conventional
methods and four different RT-PCR assays were used: a panfungal, a
pandermatophyte and two specific assays for detecting Candida spp. and
Aspergillus spp. Fungal elements were visualised in 58% of the samples, and 54%
of cultures were positive. Panfungal and pandermatophyte RT-PCR were positive in
28% and 60%, respectively, and the sensitivity relative to positive cultures was
47% and 90%. Candida spp. were detected in 76% of samples analysed and
Aspergillus spp. in 60%. These species were also present in 80% of control cases.
In conclusion, molecular techniques were useful but showed limitations. The
panfungal assay showed a low sensitivity, the pandermatophyte assay was sensitive
and specific but did not allow for differentiation among species of
dermatophytes. Finally, the role of non-dermatophyte species detected by using
specific RT-PCR techniques should be carefully analysed as these species were
also present in healthy nails.
PMID- 28508390
TI - Elevated maternal placental protein 13 serum levels at term of pregnancy in
postpartum major hemorrhage (>1000 mLs). A prospective cohort study.
AB - PROBLEM: To compare placental protein 13 (PP13) levels in the serum of women with
primary postpartum hemorrhage (PPH) with a control population. METHODS: A
prospective cohort study was conducted between May 2014 and May 2016 and included
435 pregnant women at term (38 weeks gestation) without any known risk factor and
with normal labor. Multiples of median (MoM) were used to evaluate differences of
the PP13 values between cases and controls. PP13 concentrations were adjusted for
maternal and neonatal weight. Multivariable analysis was used to detect
independent contribution of predictors of PPH. RESULTS: Fifteen had a major PPH
>1000 mLs and represented the cases of the study. They were matched with 399
controls. Twenty-one patients who had a minor PPH (500-1000 mLs) were excluded.
The mean observed rank in the PPH group was higher than that of controls (28.5 vs
13.5, P-value=.01). PP13 MoM values adjusted for maternal weight were higher than
expected being 1.44+/-0.45 in PPH cases and 1.00+/-0.59 in controls (P-value
.008). This difference was still significant even after adjustment for neonatal
weight that represented a confounding variable. CONCLUSION: Higher PP13 levels
are independently associated with major PPH >1000 mLs.
PMID- 28508391
TI - Burkitt lymphoma.
PMID- 28508392
TI - Polyoxometalate-Engineered Building Blocks with Gold Cores for the Self-Assembly
of Responsive Water-Soluble Nanostructures.
AB - The controlled assembly of gold nanoparticles (AuNPs) with the size of quantum
dots into predictable structures is extremely challenging as it requires the
quantitatively and topologically precise placement of anisotropic domains on
their small, approximately spherical surfaces. We herein address this problem by
using polyoxometalate leaving groups to transform 2 nm diameter gold cores into
reactive building blocks with hydrophilic and hydrophobic surface domains whose
relative sizes can be precisely tuned to give dimers, clusters, and larger
micelle-like organizations. Using cryo-TEM imaging and 1 H DOSY NMR spectroscopy,
we then provide an unprecedented "solution-state" picture of how the micelle-like
structures respond to hydrophobic guests by encapsulating them within 250 nm
diameter vesicles whose walls are comprised of amphiphilic AuNP membranes. These
findings provide a versatile new option for transforming very small AuNPs into
precisely tailored building blocks for the rational design of functional water
soluble assemblies.
PMID- 28508393
TI - Reversed single string technique for coronary bifurcation stenting-First report
of case demonstrations in vitro.
AB - OBJECTIVES: This work reports the concept and the practical feasibility of
Reversed Single String bifurcation stenting technique by demonstrating three in
vitro cases. BACKGROUND: Provisional T stenting is the most used interventional
technique to treat coronary bifurcation lesions. However, after main branch (MB)
stenting, treatment of the side branch (SB) may become indicated to provide a
good final result. Currently applied methods all have their structural
limitations with respect to wall coverage, multiple strut layers, poor apposition
rate. We reasoned that reversing the Single String technique principle could be
used as a bail out after inadequate provisional T stenting. METHODS AND RESULTS:
We simulated in three silicone bifurcation phantoms a scenario whereby stenting
the SB becomes indicated after provisional T stenting. Thereafter, as first step
of Reversed Single String, a stent was deployed into the SB ostium with one
single protruding stent-cell into the MB. After wiring that stent-cell and
positioning MB balloon across it, final kissing balloon dilation was performed.
Results of the in vitro Reversed Single String cases were evaluated by X-ray
angiography, optical frequency domain imaging, and 3-Dimensional (3D)
reconstruction (OFDI). Each case was successfully performed and completed. In the
bifurcation area, perfect apposition was documented in over 81% of the struts.
Malapposition remained below 4% of struts in each case. 3D OFDI reconstruction
did not reveal any strut fracture. CONCLUSION: This report suggests that Reversed
Single String technique might offer a potential bail out solution for provisional
T-stenting cases, when treatment of the SB becomes indicated. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28508395
TI - Reiteration of the Statistical Basis of DNA Source Attribution Determinations in
View of the Attorney General's Directive on "Reasonable Scientific Certainty"
Statements.
PMID- 28508394
TI - Disentangling the effects of date, individual, and territory quality on the
seasonal decline in fitness.
AB - The seasonal timing of reproduction is a major fitness factor in many organisms.
Commonly, individual fitness declines with time in the breeding season. We
investigated three suggested but rarely tested hypotheses for this seasonal
fitness decline: (1) time per se (date hypothesis), (2) late breeders are of
lower quality than early ones (individual quality hypothesis), and (3) late
breeders are breeding at poorer territories than early breeders (territory
quality hypothesis). We used Bayesian variance component analyses to examine
reproductive output (breeding success, number fledged, and number of recruits)
from repeated observations of female Northern Wheatears (Oenanthe oenanthe) and
individual territories from a 20-yr population study. The major part of the
observed seasonal decline in reproductive output seemed to be driven by date
related effects, whereas female age and territory type (i.e., known indicators of
temporary quality) contributed to a smaller degree. Other, persistent effects
linked to individual and territory identity did not show any clear patterns on
the seasonal decline in reproductive output. To better disentangle the quality
effects (persistent and temporary) of individual and territory from effects
caused by the deterioration of the environment we suggest a protocol combining
experimental manipulation of breeding time with a variance-covariance
partitioning method used here.
PMID- 28508396
TI - Three-Year-Olds' Reactions to a Partner's Failure to Perform Her Role in a Joint
Commitment.
AB - When children make a joint commitment to collaborate, obligations are created.
Pairs of 3-year-old children (N = 144) made a joint commitment to play a game. In
three different conditions the game was interrupted in the middle either because:
(a) the partner child intentionally defected, (b) the partner child was ignorant
about how to play, or (c) the apparatus broke. The subject child reacted
differently in the three cases, protesting normatively against defection (with
emotional arousal and later tattling), teaching when the partner seemed to be
ignorant, or simply blaming the apparatus when it broke. These results suggest
that 3-year-old children are competent in making appropriate normative
evaluations of intentions and obligations of collaborative partners.
PMID- 28508397
TI - Why is the female population more susceptible to cholestasis-induced liver injury
Could it be long noncoding RNA H19?
PMID- 28508398
TI - Effect of electromyographic biofeedback as an add-on to pelvic floor muscle
exercises on neuromuscular outcomes and quality of life in postmenopausal women
with stress urinary incontinence: A randomized controlled trial.
AB - AIMS: To compare the efficacy of pelvic floor muscle exercises (PFME) with and
without electromyographic biofeedback (BF) in increasing muscle strength,
improving myoelectric activity, and improving pre-contraction and quality of life
in postmenopausal women with stress urinary incontinence. METHODS: Randomized
controlled trial of 49 postmenopausal women with stress urinary incontinence.
Participants were allocated across three groups: control, PFME alone, and PFME +
BF. Forty-five women completed the study (14 control, 15 PFME, 16 PFME + BF; mean
age 58.26 years). Outcome assessment was carried out using digital palpation
(modified Oxford grading scale), electromyography, and the International
Consultation Incontinence Questionnaire-Short Form (ICIQ-SF) quality of life
instrument. The treatment protocol consisted of eight twice-weekly, 20-min one-on
one sessions. Controls were assessed only at baseline and after 1 month. RESULTS:
The PFME and PFME + BF groups exhibited significant increases in muscle strength
(Oxford scale) (P < 0.0001), precontraction while coughing (P < 0.0001), maximum
voluntary contraction, duration of endurance contraction, and ICIQ-SF scores (P <
0.0001). PFME + BF was associated with significantly superior improvement of
muscle strength, precontraction while coughing, maximum voluntary contraction,
and duration of endurance contraction as compared to PFME alone (P < 0.05).
CONCLUSIONS: This preliminary study suggests that pelvic floor muscle training,
with and without biofeedback, is associated with increased muscle strength,
myoelectric activity, precontraction of pelvic floor muscles, and improved
quality of life in postmenopausal women with stress urinary incontinence.
PMID- 28508399
TI - HDlive Flow silhouette mode and spatiotemporal image correlation for diagnosing
congenital heart disease.
PMID- 28508400
TI - Vascular endothelial growth factor receptor 3 is a novel marker differing CD138
positive and CD138-negative multiple myeloma cells.
PMID- 28508401
TI - Oxygen-Deficient Titanium Dioxide Nanosheets as More Effective Polysulfide
Reservoirs for Lithium-Sulfur Batteries.
AB - In this work, oxygen-deficient anatase TiO2 nanosheets (A-TiO2-x NSs) are
proposed as a substrate to improve the electrochemical properties of sulfur
electrodes for lithium-sulfur (Li-S) batteries. The A-TiO2-x NSs are prepared by
partly reducing pristine TiO2 nanosheets (A-TiO2 NSs) in NaBH4 solution. With
some oxygen vacancies on the surface of the TiO2 nanosheets, A-TiO2-x NSs not
only promote electronic transfer, but also act as more effective polysulfide
reservoirs to minimize the dissolution of lithium polysulfides (LiPSs) than the A
TiO2 NSs control. Hence, upon utilization as modifiers for cathodes of Li-S
batteries, the A-TiO2-x NSs-modified sulfur (A-TiO2-x NSs-S) cathode exhibits a
higher reversible specific capacity and greater cycling performance and rate
capability than the A-TiO2 NSs-modified one (A-TiO2 NSs-S). For example, A-TiO2-x
NSs-S delivers an initial specific capacity of 1277.1 mAh g-1 at 0.1 C and
maintains a stable Coulombic efficiency of approximately 99.2 % after the first
five cycles; these values are higher than those of 997.3 mAh g-1 and around 96.7
%, respectively, for A-TiO2 NSs-S. The enhanced electrochemical properties of the
A-TiO2-x NSs-S cathode can be ascribed mainly to the more effective adsorption of
dissolvable and diffused LiPSs by the oxygen vacancies. Therefore, utilization of
the structure of oxygen vacancies in Li-S batteries demonstrates great prospects
for practical application.
PMID- 28508402
TI - Risk factors for human immunodeficiency virus among blood donors in Cameroon:
evidence for the design of an Africa-specific donor history questionnaire.
AB - BACKGROUND: In sub-Saharan Africa improving the deferral of at-risk blood donors
would be a cost-effective approach to reducing transfusion-transmitted human
immunodeficiency virus (HIV) infections. We performed a pilot case-control study
to identify the risk factors for HIV infection and to develop an adapted donor
history questionnaire (DHQ) for sub-Saharan Africa. STUDY DESIGN AND METHODS: We
recruited 137 HIV-positive donors (cases) and 256 HIV-negative donors (controls)
and gathered risk factor data using audio computer-assisted self-interview.
Variables with univariate associations were entered into a logistic regression
model to assess independent associations. A scoring scheme to distinguish between
HIV-positive and HIV-negative donors was developed using receiver operating
characteristics curves. RESULTS: We identified 16 risk factors including sex with
sex worker, past history or treatment for sexually transmitted infections, and
having a partner who used injected or noninjected illegal drugs. Two novel risks
were related to local behavior: polygamy (odds ratio [OR], 22.7; 95% confidence
interval [CI], 5.9-86.7) and medical or grooming treatment on the street (OR,
1.8; 95% CI, 1.0-3.0). Using the 16 selected items the mean scores (>100) were
82.6 +/- 6.7 (range, 53.2-95.1) and 85.1 +/- 5.2 for HIV-negative donors versus
77.9 +/- 6.8 for HIV-positive ones (p = 0.000). Donors who scored between 80 and
90 were more likely to be HIV negative than those who scored less (OR, 31.4; 95%
CI, 3.1-313.9). CONCLUSION: We identified both typical and novel HIV risk factors
among Cameroonian blood donors. An adapted DHQ and score that discriminate HIV
negative donors may be an inexpensive means of reducing transfusion-transmitted
HIV through predonation screening.
PMID- 28508403
TI - Physiochemical and functional properties of chum salmon (Oncorhynchus keta) skin
gelatin extracted at different temperatures.
AB - BACKGROUND: Aquatic source gelatins are gaining more attention due to the
advantages in safety and religion acceptability compared with mammalian sources.
For understanding the effects of extracting temperature on gelatins from chum
salmon (Oncorhynchus keta) skins (GCSS), gelatins were extracted at temperatures
from 40 to 90 degrees C and the physiochemical properties of GCSS were
investigated. RESULTS: GCSS yield increased while imino acids content declined as
the increase of temperature. GCSS40, 50 and 60 showed strong beta-, alpha1- and
alpha2-chains but the three faded in GCSS70, 80 and 90, with the presence of low
molecular weight fragments. Amides A, I and III were shifted to higher wavenumber
in GCSS70, 80 and 90 compared with that of GCSS40, 50 and 60. X-ray diffraction
showed lower intensity of peak at 7 degrees in GCSS80 and 90 than in the other
GCSS. Gel strength declined while a*, b* and DeltaE* value increased as
temperature increased. Foam expansion and stability of GCSS40, 50 and 60 were
lower than those of GCSS70, 80 and 90. Emulsion activity and stability decreased
as temperature increased. CONCLUSION: Extracting temperature greatly affected
yield, molecular composition and functionalities of GCSS. A temperature lower
than 50 degrees C is recommended for GCSS extraction. (c) 2017 Society of
Chemical Industry.
PMID- 28508404
TI - Changes in biomechanics of skiing at maximal velocity caused by simulated 20-km
skiing race using V2 skating technique.
AB - This study investigated how the fatigue caused by a 20-km simulated skating cross
country skiing race on snow affects the final spurt performance from a
biomechanical perspective. Subjects performed a 100-m maximal skiing trial before
and at the end of the simulated race. Cycle characteristics, ground reaction
forces from skis and poles, and muscle activity from eight muscles were recorded
during each trial. Results showed that subjects were in a fatigued state after
the simulated race manifested by 11.6% lower skiing speed (P<.01). The lower
skiing speed was related to an 8.0% decrease in cycle rate (P<.01), whereas cycle
length was slightly decreased (tendency). In temporal patterns, relative kick
time was increased (10.9%, P<.01) while relative poling time was slightly
decreased (tendency). Vertical ski force production decreased by 8.3% while pole
force production decreased by 26.0% (both, P<.01). Muscle activation was
generally decreased in upper (39.2%) and lower body (30.7%) (both, P<.01).
Together these findings show different responses to fatigue in the upper and
lower body. In ski forces, fatigue was observed via longer force production times
while force production levels decreased only slightly. Pole forces showed equal
force production times in the fatigued state while force production level
decreased threefold compared to the ski forces.
PMID- 28508405
TI - Detection of cytological changes in oral mucosa among users of smokeless tobacco
(shamma) in the KSA.
AB - BACKGROUND AND AIM: Smokeless tobacco (ST) use is a major cause of cytological
changes in the oral mucosa. ST products, such as shamma, which is prevalent in
southern Saudi Arabia, raise concerns about the adverse health effects among its
users. We evaluated the cytological changes in the oral mucosa of users and
nonusers of shamma in the city of Najran, using Papanicolaou staining. MATERIALS
AND METHODS: We designed questionnaires and consent forms for this study that
were administered to a total of 397 participants, comprising 250 nonusers of
shamma (controls) and 147 shamma users (cases). Buccal cell smears were collected
from all participants, fixed, and Papanicolaou stained. Photomicrographs were
taken of all stained smears, and samples were subsequently diagnosed. RESULTS:
Various cytological changes were detected among both cases and controls: atypia
(2.0%, 1.2%, respectively), keratinisation (0.7%, 0%, respectively), inflammation
(13.6%, 10.8%, respectively), and infection (4.1%, 3.6%, respectively).
CONCLUSION: The results showed higher percentages of cytological changes among
shamma users compared with nonusers; however, the differences were not
statistically significant. Habitual use of other substances in the control group
could be a confounding factor given this geographic region and the cytological
changes we detected in both cases and controls. Diagn. Cytopathol. 2017;45:693
699. (c) 2017 Wiley Periodicals, Inc.
PMID- 28508406
TI - Hypericum perforatum L. supplementation protects sciatic nerve injury-induced
apoptotic, inflammatory and oxidative damage to muscle, blood and brain in rats.
AB - OBJECTIVES: This study was conducted to explore whether Hypericum perforatum L.
(HPL) as a potent antioxidant protects against oxidative stress, cytokine
production and caspase expression in muscle (soleus), brain and blood of sciatic
nerve injury (SNI)-induced rats. METHODS: Thirty-five rats were equally divided
into five groups. The first and second were used as untreated control and sham
control groups, respectively. The third, fourth and fifth were sham + HPL, SNI
and SNI + HPL groups, respectively. The third and fifth groups received 30 mg/kg
HPL via gastric gavage for 28 days. KEY FINDINGS: High levels of muscle, brain
and red blood cell (RBC) lipid peroxidation, plasma cytokine (TNF-alpha, IL-1beta
and IL-2), muscle PARP, caspase 3 and 9 expression levels were decreased by HPL
treatments. Plasma glutathione peroxidase (GPx) activity, alpha-tocopherol and
melatonin, muscle, brain and RBC reduced glutathione (GSH) concentrations were
decreased by SNI induction, whereas their values were increased by HPL
treatments. beta-carotene and retinol concentrations did not change in the five
groups. CONCLUSION: HPL may play a role in preventing SNI-induced inflammatory,
oxidative and apoptotic blood, muscle and brain damages through upregulation of
the GSH and GPx values but downregulation of PARP, caspase level and cytokine
production in SNI-induced rats.
PMID- 28508408
TI - Variations in status of preparation of personal protective equipment for
preventing norovirus gastroenteritis in long-term care facilities for the
elderly.
AB - RATIONALE, AIM, AND OBJECTIVES: Residents of long-term care facilities are highly
susceptible to norovirus gastroenteritis, and each facility is concerned about
the need to implement norovirus infection control. Among control measures,
personal protective equipment (PPE), such as disposable gloves and masks, plays a
major role in reducing infectious spread. However, the preparation status of PPE
in facilities before infection outbreaks has not been reported. The aim was to
clarify the implementation status of preventive measures for norovirus
gastroenteritis and the cost of preparing the necessary PPE in long-term care
facilities. METHOD: A questionnaire survey of facilities affiliated with the
Kyoto Prefecture and Osaka Prefecture branches of the Japan Association of
Geriatric Health Services Facilities was conducted. The survey items were the
characteristics of the facility, whether preventive measures had been implemented
for norovirus gastroenteritis from October through the following March in both
2009 and 2010, and the quantities and unit prices of PPE prepared for preventive
measures. RESULTS: Twenty-six (11.2%) of 232 surveyed facilities (as of August
2011) answered the survey. Among them, 24 (92.3%) in 2009 and 25 (96.2%) in 2010
reported having implemented preventive measures for norovirus gastroenteritis,
while 21 facilities (80.8%) in 2009 and 22 facilities (84.6%) in 2010 had
prepared PPE. The median total cost for preparing the PPE needed for the
preventive measures was US $2601 (range US $221-9192) in 2009 and US $3904 (range
US $305-6427) in 2010. CONCLUSION: Although the results need careful
interpretation because of the low response rate, most of the surveyed long-term
care facilities had implemented preventive measures for norovirus
gastroenteritis. However, the cost of preparing the PPE needed for the preventive
measures varied among the facilities.
PMID- 28508409
TI - Mycobacterium chimaera left ventricular assist device infections.
AB - A global outbreak of invasive Mycobacterium chimaera infections after cardiac
surgery has recently been linked to bioaerosols from contaminated heater-cooler
units. The majority of cases have occurred after valvular surgery or aortic graft
surgery and nearly half have resulted in death. To date, infections in patients
with left ventricular assist devices (LVADs) have not been characterized in the
literature. We report two cases of device-associated M. chimaera infection in
patients with continuous-flow LVADs and describe challenges related to diagnosis
and management in this population.
PMID- 28508411
TI - The relationship between symptom prevalence, body image, and quality of life in
Asian gynecologic cancer patients.
AB - OBJECTIVE: Gynecologic cancer is associated with long-term effects that can be
both physical and emotional. We examined symptom prevalence and body image
disturbance in patients with gynecologic cancer and their association with
quality of life. Predictors of clinically-relevant body image disturbance were
examined. METHODS: A sample of patients in Singapore (n = 104) was assessed for
symptom prevalence, quality of life, and body image dissatisfaction. Clinical
factors were extracted from medical records. RESULTS: The most frequently
reported symptoms were fatigue, abdominal bloatedness, weight gain, constipation,
hot flashes, and pelvic pain. Approximately one quarter patients reported feeling
less physically attractive and dissatisfied with their body. Ordinary least
squares regression indicated that symptom prevalence alone predicted physical
well-being, b = -1.09, P < .001, 95% CI, -1.45 to -0.73, and functional well
being, b = -0.88, P < .001, 95% CI, -1.32 to -0.45. Body image dissatisfaction
alone significantly predicted emotional well-being, b = -0.21, P < .01, 95% CI,
0.35 to -0.06. Younger age was a significant risk factor for clinically-relevant
score of body image distress, OR = 0.95 per year older, 95% CI, 0.92 to 0.99, P =
.02. CONCLUSIONS: Symptom prevalence and body image dissatisfaction were
associated with different domains of quality of life. Emotional well-being of
patients was better explained by body image, rather than extent of symptoms
experienced. Patients who are younger appear particularly susceptible to body
image disturbance.
PMID- 28508407
TI - Structural conservation of the PIN domain active site across all domains of life.
AB - The PIN (PilT N-terminus) domain is a compact RNA-binding protein domain present
in all domains of life. This 120-residue domain consists of a central and
parallel beta sheet surrounded by alpha helices, which together organize 4-5
acidic residues in an active site that binds one or more divalent metal ions and
in many cases has endoribonuclease activity. In bacteria and archaea, the PIN
domain is primarily associated with toxin-antitoxin loci, consisting of a toxin
(the PIN domain nuclease) and an antitoxin that inhibits the function of the
toxin under normal growth conditions. During nutritional or antibiotic stress,
the antitoxin is proteolytically degraded causing activation of the PIN domain
toxin leading to a dramatic reprogramming of cellular metabolism to cope with the
new situation. In eukaryotes, PIN domains are commonly found as parts of larger
proteins and are involved in a range of processes involving RNA cleavage,
including ribosomal RNA biogenesis and nonsense-mediated mRNA decay. In this
review, we provide a comprehensive overview of the structural characteristics of
the PIN domain and compare PIN domains from all domains of life in terms of
structure, active site architecture, and activity.
PMID- 28508412
TI - Nicotine withdrawal syndrome in a newborn baby after maternal use of oral applied
moist tobacco (snus), should result in greater awareness to the use of snus among
pregnant women.
PMID- 28508410
TI - Lipid distribution, composition and uptake in bovine articular cartilage studied
using Raman micro-spectrometry and confocal microscopy.
AB - The distribution and composition of endogenous lipids in articular cartilage and
transport of exogenous fatty acids have been investigated on a microscopic scale
in fresh bovine articular cartilage. To investigate the distribution and
composition of the endogenous lipids, hyperspectral Raman maps were taken of
chondrocytes and their surrounding matrix in both the deep and superficial zones.
These revealed differences in both lipid distribution and composition between the
two zones. Extracellular lipid was observed surrounding the cells in the
superficial zone but not in the deep zone. Additionally, intracellular lipid
droplets were observed that were larger and more numerous in the deep zone (P =
0.01). The extracellular lipid was primarily free saturated fatty acid, whereas
the cellular lipid droplets contained triglycerides with unsaturated fatty acid
chains. Fatty acid uptake and transport were investigated by incubating cartilage
samples in Dulbecco's modified Eagle's medium containing fluorescently labelled
palmitate for a range of times and temperatures. After incubation, the palmitate
distribution was imaged using confocal microscopy. Palmitate accumulated
preferentially in the territorial matrix only in the superficial zone where the
concentration was up to 100-fold greater than that in the bulk matrix (P =
0.001). Palmitate uptake by the chondrocytes in both zones showed differential
temperature sensitivity (P = 0.05), which would support the idea that cells take
up palmitate by both active and passive mechanisms. The study reveals large
differences between chondrocytes in the superficial and deep zones in their lipid
content, in their extracellular lipid environment and in their access to
exogenous fatty acids.
PMID- 28508415
TI - Proptosis secondary to third nerve palsy.
PMID- 28508414
TI - Cervical cerclage placed before 14 weeks gestation in women with one previous
midtrimester loss: A population-based cohort study.
AB - BACKGROUND: Cervical cerclage is used in an attempt to reduce recurrence risk of
preterm birth, but evidence for use is limited. AIMS: To compare pregnancy
outcomes among women with a single previous midtrimester delivery when managed
with or without a cervical cerclage. MATERIALS AND METHODS: Population-based
cohort study of all women in New South Wales, Australia with a singleton
pregnancy ending in birth/miscarriage >=14 and <28 weeks, between 2003 and 2011.
Modified Poisson regression was used to compare outcomes in the next subsequent
pregnancy, for women with a cerclage inserted <14 weeks, and those without
cerclage. The primary outcome was gestational age <37 weeks at birth/miscarriage
in the next pregnancy. Secondary outcomes included: maternal morbidity, preterm
prelabour rupture of membranes (PPROM), stillbirth/neonatal death and composite
neonatal morbidity for liveborn infants >=28 weeks. Adjusted risk ratios (ARR)
and 95% confidence intervals (CI) were determined. RESULTS: Five thousand, six
hundred and ninety-eight births/miscarriages were potential index deliveries. Of
these, 2175 women had an eligible subsequent pregnancy: 108 received cerclage at
<14 weeks gestation, 2067 did not. Women with cerclage were significantly more
likely to deliver <37 weeks than those without (39.8% vs 19.3%, ARR 1.92, 95% CI
1.48-2.48), and had increased risks of PPROM (ARR 4.38, 95% CI 2.62-7.32) and
stillbirth/neonatal death (ARR 2.20, 95% CI 1.02-4.73). Following cerclage,
liveborn infants >=28 weeks had double the risk of severe morbidity (ARR 2.54,
95% CI 1.55-4.16). CONCLUSIONS: In women with a single previous midtrimester
delivery, cervical cerclage <14 weeks gestation in subsequent pregnancy was
associated with worse pregnancy outcomes.
PMID- 28508413
TI - Serological weak D phenotypes: a review and guidance for interpreting the RhD
blood type using the RHD genotype.
AB - Approximately 0.2-1% of routine RhD blood typings result in a "serological weak D
phenotype." For more than 50 years, serological weak D phenotypes have been
managed by policies to protect RhD-negative women of child-bearing potential from
exposure to weak D antigens. Typically, blood donors with a serological weak D
phenotype have been managed as RhD-positive, in contrast to transfusion
recipients and pregnant women, who have been managed as RhD-negative. Most
serological weak D phenotypes in Caucasians express molecularly defined weak D
types 1, 2 or 3 and can be managed safely as RhD-positive, eliminating
unnecessary injections of Rh immune globulin and conserving limited supplies of
RhD-negative RBCs. If laboratories in the UK, Ireland and other European
countries validated the use of potent anti-D reagents to result in weak D types
1, 2 and 3 typing initially as RhD-positive, such laboratory results would not
require further testing. When serological weak D phenotypes are detected,
laboratories should complete RhD testing by determining RHD genotypes (internally
or by referral). Individuals with a serological weak D phenotype should be
managed as RhD-positive or RhD-negative, according to their RHD genotype.
PMID- 28508416
TI - Frame-shift variant in the CHRNE gene in a juvenile dog with suspected myasthenia
gravis-like disease.
PMID- 28508417
TI - Score of Toxic Epidermal Necrosis Predicts the Outcomes of Pediatric Epidermal
Necrolysis.
AB - BACKGROUND/OBJECTIVES: Epidermal necrolysis (Stevens-Johnson syndrome and toxic
epidermal necrolysis) includes immune-mediated, life-threatening inflammatory
blistering disorders that can affect children. The Score of Toxic Epidermal
Necrosis (SCORTEN) tool has accurately predicted the outcome of these disorders
in adults but has not been tested in children. METHODS: We performed a
retrospective chart review to compare the accuracy of the adult SCORTEN tool with
that of two modifications tailored to children in predicting disease outcome.
RESULTS: The longer the patient's median length of hospital stay was, the higher
the adult and two proposed pediatric SCORTENs were. In addition, all patients who
died had SCORTENs greater than 4. CONCLUSION: The pediatric-modified tools were
not superior to the adult SCORTEN, which accurately predicted outcome.
PMID- 28508418
TI - Quantitative analysis of cervical texture by ultrasound in mid-pregnancy and
association with spontaneous preterm birth.
AB - OBJECTIVE: New tools are required to improve the identification of women who are
at increased risk for spontaneous preterm birth (sPTB). Quantitative analysis of
tissue texture on ultrasound has been used to extract robust features from the
ultrasound image to detect subtle changes in its microstructure. This may be
applied to the cervix. The aim of this study was to determine if there is an
association between quantitative analysis of cervical texture (CTx) on mid
trimester ultrasound and sPTB < 37 + 0 weeks' gestation. METHODS: This was a
single-center nested case-control study of a prospective cohort of 677
consecutive women with singleton pregnancy assessed between 19 + 0 and 24 + 6
weeks' gestation. Women at increased risk for sPTB were included unless they
received treatment to prevent sPTB. Women who delivered < 37 + 0 weeks (sPTB)
were considered as cases and were matched in a 1: 10 ratio with randomly selected
contemporary controls who delivered at term. For each woman, one ultrasound image
of the cervix was obtained for which quality was assessed, cervical length (CL)
measured offline and a region of interest in the midportion of the anterior
cervical lip delineated for use in local binary patterns analysis of CTx. A
learning algorithm was developed to obtain the combination of CTx features best
associated with sPTB based on feature transformation and discriminant analysis
regression. The ability of the learning algorithm to predict sPTB was evaluated
using a leave-one-out cross-validation technique, which produced a CTx-based
score for each participant. Receiver-operating characteristics (ROC) curves were
produced and sensitivity, specificity, and positive and negative likelihood
ratios were calculated for the optimal cut-off based on the ROC curve. The
results were compared with those obtained for CL. Investigators studying the
images were blinded to pregnancy outcome at all times. RESULTS: Images from 310
women (27 cases and 283 controls) were of sufficient quality and included in the
study. Median CTx-based score was significantly lower in cases compared with
controls (-1.01 vs -0.07, P <= 0.0001). CTx-based score maintained its
significant association with sPTB after adjusting for possible confounders
(history of sPTB, conization or Mullerian malformation, and CL < 25 mm). CTx
based score was a better predictor of sPTB (AUC, 0.77; 95% CI, 0.66-0.87) than
was CL (AUC, 0.60; 95% CI, 0.47-0.72) (P = 0.03). Median CL was similar for cases
and controls (37.7 vs 38.6 mm, P = 0.26), although cases were more likely to have
CL < 25 mm (18.5% vs 0.4%, P < 0.001). CONCLUSION: Quantitative analysis of CTx
enables the extraction of information relevant to sPTB from ultrasound images to
generate a CTx-based score that is associated independently with sPTB. Copyright
(c) 2017 ISUOG. Published by John Wiley & Sons Ltd.
PMID- 28508420
TI - Synthesis of beta-Lactams by Palladium(0)-Catalyzed C(sp3 )-H Carbamoylation.
AB - A general and user-friendly synthesis of beta-lactams is reported that makes use
of Pd0 -catalyzed carbamoylation of C(sp3 )-H bonds, and operates under
stoichiometric carbon monoxide in a two-chamber reactor. This reaction is
compatible with a range of primary, secondary and activated tertiary C-H bonds,
in contrast to previous methods based on C(sp3 )-H activation. In addition, the
feasibility of an enantioselective version using a chiral phosphonite ligand is
demonstrated. Finally, this method can be employed to synthesize valuable
enantiopure free beta-lactams and beta-amino acids.
PMID- 28508419
TI - Case-control study shows that neonatal pneumococcal meningitis cannot be
distinguished from group B Streptococcus cases.
AB - AIM: Streptococcus pneumoniae (S. pneumoniae) is sometimes implicated in neonatal
bacterial meningitis. This study described the demographic, clinical and
biological features of neonatal S. pneumoniae meningitis and compared
pneumococcal and group B streptococcal (GBS) neonatal meningitis. METHODS: We
conducted a case-control study that compared neonates, aged one to 28 days with
S. pneumoniae meningitis or GBS meningitis. Each case with S. pneumoniae was
randomly matched to four control patients with GBS by age group and study year.
RESULTS: From 2001 to 2013, the national French paediatric network, which
comprises 227 paediatric wards, recorded 831 neonatal cases of meningitis. S.
pneumoniae (n = 18, 2.2%) was the fifth infection cause after GBS (n = 464,
55.8%), Escherichia coli (n = 232, 27.9%), Neisseria meningitidis (n = 23, 2.8%)
and Listeria monocytogenes (n = 20, 2.4%). Neonatal pneumococcal and GBS
meningitis did not differ in demographic data or clinical and biological
characteristics. All S. pneumoniae strains were fully susceptible to cefotaxime,
and we observed a decrease of 13-valent pneumococcal conjugate vaccine (PCV13)
serotypes (88.9%-20.0%) after PCV13 implementation. CONCLUSION: Clinically and
biologically, neonatal pneumococcal meningitis could not be distinguished from
GBS cases. A herd effect of PCV13 implementation was suggested by the decrease in
the prevalence of vaccine serotypes.
PMID- 28508422
TI - Age-related inequalities in health and healthcare: the life stages approach.
AB - How should healthcare systems prepare to care for growing numbers and proportions
of older people? Older people generally suffer worse health than younger people
do. Should societies take steps to reduce age-related health inequalities? Some
express concern that doing so would increase age-related inequalities in
healthcare. This paper addresses this debate by (1) presenting an argument in
support of three principles for distributing scarce resources between age groups;
(2) framing these principles of age group justice in terms of life stages; and
(3) indicating policy implications that merit further attention in light of
rapidly aging societies.
PMID- 28508421
TI - Subversion of host kinases: a key network in cellular signaling hijacked by
Helicobacter pylori CagA.
AB - Helicobacter pylori is a paradigm of persistent pathogens and major risk factor
for developing severe diseases including adenocarcinoma in the human stomach. An
important bacterial factor linked to gastric disease progression is the cag
pathogenicity island-encoded type-IV secretion system (T4SS) effector protein
CagA. Translocated CagA undergoes tyrosine phosphorylation at EPIYA-motifs and
then activates or inactivates multiple host signaling proteins in a
phosphorylation-dependent and phosphorylation-independent fashion. In this way,
intracellular CagA acts as a 'masterkey' or 'picklock', which evolved during
evolution to hijack key host cell signal transduction functions. Crucial targets
of CagA represent a variety of serine/threonine and tyrosine kinases, which
control major checkpoints of eukaryotic signaling. Here we review the signal
transmission by translocated CagA on multiple receptor kinases (c-Met and EGFR)
and non-receptor kinases (Src, Abl, Csk, aPKC, Par1, PI3K, Akt, FAK, GSK-3, JAK,
PAK1, PAK2 and MAP kinases), manipulating a selection of fundamental processes in
the human gastric epithelium such as cell adhesion, polarity, proliferation,
motility, receptor endocytosis, cytoskeletal rearrangements, apoptosis,
inflammation and cell cycle progression. This enormous complexity generates a
highly remarkable and puzzling scenario during H. pylori infection. The
contribution of these signaling pathways to bacterial survival, persistence and
gastric pathogenesis is discussed.
PMID- 28508423
TI - Oxoborane (RBO) Complexation and Concomitant Electrophilic Bond Activation
Processes.
AB - Donor-acceptor complexes of the oxoboranes ClB=O and HOB=O were synthesized and
each feature short multiply bonded B=O linkages. The retention of high Lewis
acidic character within these encapsulated monomeric oxoboranes was manifested by
their ability to support C-F and Si-O bond activation/functionalization. The
reported ClB=O complexes can be regarded as synthetic surrogates of the [BO]+
cation, an inorganic analogue of CO.
PMID- 28508424
TI - Computational site-directed mutagenesis studies of the role of the hydrophobic
triad on substrate binding in cholesterol oxidase.
AB - Cholesterol oxidase (ChOx) is a flavoenzyme that oxidizes and isomerizes
cholesterol (CHL) to form cholest-4-en-3-one. Molecular docking and molecular
dynamics simulations were conducted to predict the binding interactions of CHL in
the active site. Several key interactions (E361-CHL, N485-FAD, and H447-CHL) were
identified and which are likely to determine the correct positioning of CHL
relative to flavin-adenine dinucleotide (FAD). Binding of CHL also induced
changes in key residues of the active site leading to the closure of the oxygen
channel. A group of residues, Y107, F444, and Y446, known as the hydrophobic
triad, are believed to affect the binding of CHL in the active site.
Computational site-directed mutagenesis of these residues revealed that their
mutation affects the conformations of key residues in the active site, leading to
non-optimal binding of CHL and to changes in the structure of the oxygen channel,
all of which are likely to reduce the catalytic efficiency of ChOx. Proteins
2017; 85:1645-1655. (c) 2017 Wiley Periodicals, Inc.
PMID- 28508425
TI - Bimetallic Nickel-Substituted Cobalt-Borate Nanowire Array: An Earth-Abundant
Water Oxidation Electrocatalyst with Superior Activity and Durability at Near
Neutral pH.
AB - There is an urgent demand to develop earth-abundant electrocatalysts for
efficient and durable water oxidation under mild conditions. A nickel-substituted
cobalt-borate nanowire array is developed on carbon cloth (Ni-Co-Bi/CC) via
oxidative polarization of NiCo2 S4 nanoarray in potassium borate (K-Bi). As a
bimetallic electrocatalyst for water oxidation, such Ni-Co-Bi/CC is superior in
catalytic activity and durability in 0.1 m K-Bi (pH: 9.2), with a turnover
frequency of 0.33 mol O2 s-1 at the overpotential of 500 mV and nearly 100%
Faradaic efficiency. To drive a geometrical catalytic current density of 10 mA cm
2 , it only needs overpotential of 388 mV, 34 mV less than that for Co-Bi/CC,
outperforming reported non-noble-metal catalysts operating under benign
conditions. Notably, its activity is maintained over 80 000 s. Density functional
theory calculations suggest that the O* to OOH* conversion is the rate
determining step and Ni substitution decreases the free energy on Co-Bi from
2.092 to 1.986 eV.
PMID- 28508426
TI - Role of transvaginal ultrasound in evaluation of ureteral involvement in deep
infiltrating endometriosis.
AB - OBJECTIVE: To assess whether routine examination of the ureters on transvaginal
sonography (TVS) can identify reliably potential silent ureteral involvement by
endometriosis and should therefore be recommended in all patients with deep
infiltrating endometriosis (DIE). METHODS: This was a prospective study of 200
consecutive patients scheduled for surgery for DIE, evaluated between January
2012 and December 2014 at a tertiary endometriosis center at Fondazione
Policlinico Universitario A. Gemelli, Rome, Italy. Routine TVS, abdominal
ultrasound and gynecological examination were performed within 3 months before
surgery, and patient history, signs and symptoms were recorded. Surgical and
histological findings were compared with the preoperative ultrasonographic
diagnosis. The main outcome of interest was the presence of ureteral dilatation
or hydronephrosis caused by endometriosis. RESULTS: Of 200 patients with DIE,
associated ureteral dilatation was diagnosed on TVS in 13 (6.5%) cases. Ureteral
involvement was confirmed intraoperatively in all 13 cases by detection of
ureteral dilatation caused by endometriotic tissue surrounding the ureter and
causing stenosis. Of the 13 patients with ureteral dilatation, renal ultrasound
detected six (46.2%) cases of hydronephrosis. Mean duration of visualization and
study of dilated ureters was 5 min (range, 3-9 min). Ureteric diameter was >= 6
mm in all cases of ureteral dilatation, with a median diameter of 6.9 mm (range,
6-18 mm). Both ureters were identified on TVS in all 200 patients with DIE.
CONCLUSIONS: Our study confirms a relatively high incidence of ureteral
involvement in patients with DIE. TVS appears to be a reliable tool for the
diagnosis of ureteral involvement and, additionally, it allows the detection of
both the level and degree of obstruction. Our findings confirm that TVS
examination is an accurate non-invasive diagnostic tool for the detection of
ureteral involvement by endometriosis. Copyright (c) 2017 ISUOG. Published by
John Wiley & Sons Ltd.
PMID- 28508428
TI - Characterization and quantitation of PVP content in a silicone hydrogel contact
lens produced by dual-phase polymerization processing.
AB - Polyvinylpyrrolidone (PVP) has been incorporated over the years into numerous
hydrogel contact lenses as both a primary matrix component and an internal
wetting agent to increase lens wettability. In this study, complementary
analytical techniques were used to characterize the PVP wetting agent component
of senofilcon A and samfilcon A contact lenses, both in terms of chemical
composition and amount present. Photo-differential scanning calorimetry (photo
DSC), gas chromatography with a flame ionization detector (GC-FID), and high
resolution/accurate mass (HR/AM) liquid chromatography-mass spectrometry (LC-MS)
techniques confirmed dual phase reaction and curing of the samfilcon A silicone
hydrogel material. Gel permeation chromatography (GPC) demonstrated that high
molecular weight (HMW) polymer was present in isopropanol (IPA) extracts of both
lenses. High-performance liquid chromatography (HPLC) effectively separated
hydrophilic PVP from the hydrophobic silicone polymers present in the extracts.
Collectively, atmospheric solids analysis probe mass spectrometry (ASAP MS),
Fourier transform infrared (FTIR) spectroscopy, 1 H nuclear magnetic resonance
(NMR) spectroscopy, GC-FID, and LC-MS analyses of the lens extracts indicated
that the majority of NVP is consumed during the second reaction phase of
samfilcon A lens polymerization and exists as HMW PVP, similar to the PVP present
in senofilcon A. GC-FID analysis of pyrolyzed samfilcon A and senofilcon A
indicates fourfold greater PVP in samfilcon A compared with senofilcon A. (c)
2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1064
1072, 2018.
PMID- 28508427
TI - Evaluation of Benefit and Tolerability of IQP-CL-101 (Xanthofen) in the
Symptomatic Improvement of Irritable Bowel Syndrome: A Double-Blinded,
Randomised, Placebo-Controlled Clinical Trial.
AB - Irritable bowel syndrome (IBS) is a functional bowel disorder of unknown
aetiology. There is currently no known cure, and pharmacological interventions
are usually targeting symptomatic relief, where natural and herbal remedies also
play a role. This study aimed to evaluate the benefit and tolerability of IQP-CL
101 in symptomatic IBS relief. A double-blinded, randomised, placebo-controlled
trial was conducted over 8 weeks. A total of 99 subjects fulfilling ROME-III
criteria for IBS were randomised into two groups, given either two IQP-CL-101
softgels or matching placebo twice daily before main meals. The primary endpoint
was the difference in change of IBS Symptom Severity Score (IBS-SSS) after an 8
week intake of IQP-CL-101 compared to placebo. After 8 weeks, subjects on IQP-CL
101 showed a significant reduction in IBS-SSS (113.0 +/- 64.9-point reduction)
compared to subjects on placebo (38.7 +/- 64.5-point reduction) (p < 0.001). A
significant improvement could be seen as early as 4 weeks. No serious adverse
events were reported throughout. IQP-CL-101 can be considered beneficial in the
improvement of IBS symptom severity, regardless of IBS type, and therefore able
to improve quality of life in patients suffering from abdominal pain and
discomfort. (c) 2017 The Authors. Phytotherapy Research published by John Wiley &
Sons Ltd.
PMID- 28508429
TI - The cross talk between cervical carcinoma cells and vascular endothelial cells
mediated by IL-27 restrains angiogenesis.
AB - PROBLEM: To explore whether cervical carcinoma cell-derived interleukin-27 (IL
27) modulates the angiogenesis of vascular endothelial cells. METHOD OF STUDY:
The expression of IL-27 in cervical cancer tissues and cervical cell lines was
analyzed by immunohistochemistry, ELISA and flow cytometry. Then, the effects of
IL-27 on the proliferation and apoptosis-related molecules and angiogenesis in
vitro of human umbilical vein endothelial cells (HUVECs) were investigated.
Finally, in vivo experiment was performed to further confirm the effects of IL
27. RESULTS: Compared with cervicitis, the cervical cancer tissues highly
expressed IL-27. Both HeLa and CaSki cells secreted IL-27, and HUVECs expressed
low levels of IL-27 receptors (IL-27R). However, the co-culture of cervical cell
lines and HUVECs led to a significant elevation of IL-27R on HUVECs. Co-culturing
with IL-27-overexpressed HeLa cells downregulated Ki-67 and Bcl-2 and upregulated
Fas expression in HUVECs. In addition, overexpression of IL-27 in HeLa cells and
CasKi cells secreted less IL-8 and could further restrict angiogenesis compared
with control cells in vitro. In the subcutaneous tumorous model of C57/BL6 mouse,
there were decreased vessel density and tumor volume when inoculation with IL-27
overexpressed TC-1 cells. CONCLUSION: This study indicates that IL-27 secreted by
cervical carcinoma cells restricts the angiogenesis in a paracrine manner in the
pathogenesis of cervical cancer.
PMID- 28508430
TI - Combined Delivery of a Lipopolysaccharide-Binding Peptide and the Heme Oxygenase
1 Gene Using Deoxycholic Acid-Conjugated Polyethylenimine for the Treatment of
Acute Lung Injury.
AB - A ternary complex comprising plasmid DNA, lipopolysaccharide-binding peptide
(LBP), and deoxycholic acid-conjugated polyethylenimine (PEI-DA) is prepared for
combinational therapy of acute lung injury (ALI). The LBP is designed as an anti
inflammatory peptide based on the lipopolysaccharide (LPS)-binding domain of HMGB
1. In vitro cytokine assays show that LBP reduces levels of proinflammatory
cytokines by inhibiting LPS. PEI-DA is synthesized as the gene carrier by
conjugation of deoxycholic acid to low-molecular weight polyethylenimine (2 kDa,
PEI2k). PEI-DA has higher transfection efficiency than high-molecular weight
polyethylenimine (25 kDa, PEI25k). The ternary complex of an HO-1 plasmid (pHO
1), PEI-DA, and LBP is prepared as a combinational system to deliver the
therapeutic gene and peptide. The transfection efficiency of the ternary complex
is higher than that of the pHO-1/PEI-DA binary complex. The ternary complex also
reduces TNF-alpha secretion in LPS-activated Raw264.7 macrophage cells.
Administration of the ternary complex into the lungs of an animal ALI model by
intratracheal injection induces HO-1 expression and reduces levels of
proinflammatory cytokines more efficiently than the pHO-1/PEI-DA binary complex
or LBP alone. In addition, the ternary complex reduces inflammation in the lungs.
Therefore, the pHO-1/PEI-DA/LBP ternary complex may be an effective treatment for
ALI.
PMID- 28508431
TI - A spatially balanced design with probability function proportional to the within
sample distance.
AB - The units observed in a biological, agricultural, and environmental survey are
often randomly selected from a finite population whose main feature is to be geo
referenced thus its spatial distribution should be used as essential information
in designing the sample. In particular our interest is focused on probability
samples that are well spread over the population in every dimension which in
recent literature are defined as spatially balanced samples. To approach the
problem we used the within sample distance as the summary index of the spatial
distribution of a random selection criterion. Moreover numerical comparisons are
made between the relative efficiency, measured with respect to the simple random
sampling, of the suggested design and some other classical solutions as the
Generalized Random Tessellation Stratified (GRTS) design used by the US
Environmental Protection Agency (EPA) and other balanced or spatially balanced
selection procedures as the Spatially Correlated Poisson Sampling (SCPS), the
balanced sampling (CUBE), and the Local Pivotal method (LPM). These experiments
on real and simulated data show that the design based on the within sample
distance selects samples with a better spatial balance thus gives estimates with
a lower sampling error than those obtained by using the other methods. The
suggested method is very flexible to the introduction of stratification and
coordination of samples and, even if in its nature it is computationally
intensive, it is shown to be a suitable solution even when dealing with high
sampling rates and large population frames where the main problem arises from the
size of the distance matrix.
PMID- 28508432
TI - Exploring Cryptic Diversity and Distribution Patterns in the Mallomonas
kalinae/rasilis Species Complex with a Description of a New Taxon-Mallomonas
furtiva sp. nov.
AB - A complex of closely related Mallomonas taxa belonging to the section Papillosae,
M. kalinae Rezacova and M. rasilis Durrschmidt, has been studied in detail by
molecular and morphometric methods. Our investigations uncovered the existence of
a new species found in water bodies in Vietnam, which we describe here as
Mallomonas furtiva sp. nov. This taxon is morphologically very similar to M.
kalinae, from which it differs by minute, but statistically significant
morphological differences on the structure of silica scales. Indeed, the
principal component analysis of morphological traits measured on silica scales
significantly separates all three species in the complex. Mallomonas kalinae and
M. furtiva differ by number of papillae on the shield and the dome, as well as by
the scale sizes. Likewise, Mallomonas rasilis and M. furtiva are primarily
differentiated by the absence of submarginal anterior ribs on silica scales of
the former species. Phylogenetic analyses showed that Mallomonas furtiva is
closely related to M. kalinae, with which it formed a highly supported lineage.
Distribution patterns of all three studied taxa are further discussed.
PMID- 28508433
TI - An investigation of the anti-inflammatory effects and a potential biomarker of
PI3Kdelta inhibition in COPD T cells.
AB - Lymphocyte numbers are increased in the lungs of chronic obstructive pulmonary
disease (COPD) patients. Phosphatidylinositol-3-kinase delta (PI3Kdelta) is
involved in lymphocyte activation. We investigated the effect of PI3Kdelta
inhibition on cytokine release from COPD lymphocytes. We also evaluated
phosphorylated ribosomal S6 protein (rS6) as a potential biomarker of PI3Kdelta
activation. Peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage
(BAL) cells isolated from healthy never smokers (HNS), smokers (S) and COPD
patients were stimulated to induce a T cell receptor response. The effects of a
PI3Kdelta specific inhibitor (GSK045) on cytokine release and rS6 phosphorylation
were measured by Luminex and flow cytometry respectively. The effects of GSK045
on cytokine production from PHA stimulated chopped lung samples were
investigated. GSK045 reduced cytokine release from PBMCs, BAL cells and chopped
lung. Inhibition was greatest in the chopped lung model, with approximately 80%
inhibition of interferon (IFN) gamma, interleukin (IL)-2, IL-17 and IL-10.
PI3Kdelta inhibition suppressed rS6 phosphorylation in unstimulated airway T
lymphocytes by up to 60%. Inhibition of PI3Kdelta suppressed T cell cytokine
production in COPD patients. rS6 phosphorylation shows potential as a biomarker
to assess PI3Kdelta activity.
PMID- 28508434
TI - Maternal arterial stiffness and fetal cardiovascular physiology in diabetic
pregnancy.
AB - OBJECTIVES: In mothers with pregestational or gestational diabetes, abnormal
arterial stiffness (stiffer arteries) has been reported. The impact of abnormal
maternal arterial stiffness on placental and fetal cardiovascular physiology is
unknown. The purpose of this study was to determine the impact of maternal
diabetes on maternal arterial stiffness and the association with fetal
cardiovascular physiology as measured by fetal echocardiography. METHODS: Between
December 2013 and January 2017 a prospective study was conducted on diabetic (but
otherwise healthy) and non-diabetic, healthy pregnant mothers aged 18-40 years at
20-28 weeks' gestation who had a normal fetal cardiac echocardiogram and
obstetric ultrasound. Clinical data were collected by means of a patient
questionnaire and measurement of blood pressure, height, weight, arterial
augmentation index (AIx) and placental and fetal cardiovascular parameters were
collected by fetal echocardiography. Descriptive statistics were calculated.
Comparisons were made using parametric and non-parametric tests between controls
and diabetic mothers. RESULTS: Twenty-three healthy pregnant controls and 43
diabetic pregnant women (22 with pregestational and 21 with gestational diabetes)
were included in the study. Maternal AIx was higher in those with diabetes than
in healthy controls (12.4 +/- 10.6% vs 4.6 +/- 7.9%; P = 0.003). Fetal aortic
valve (AoV) velocity time integral (VTI) was higher in fetuses whose mothers had
diabetes than in those with non-diabetic mothers (7.7 +/- 1.9 cm vs 6.3 +/- 3.0
cm; P = 0.022). Left ventricular (LV) myocardial performance index (MPI) was
lower in diabetic pregnancies than in controls (0.40 +/- 0.09 vs 0.46 +/- 0.11; P
= 0.021). Umbilical artery (UA) resistance index (RI) was lower in diabetic
pregnancies with glycated hemoglobin (HbA1c) levels >= 6.5% than in those with
HbA1c levels < 6.5% (0.69 +/- 0.06, n = 15 vs 0.76 +/- 0.08, n = 21; P = 0.009)
but not at higher HbA1C cut-offs. No correlation between AIx and AoV-VTI, LV-MPI
or UA-RI was found. CONCLUSIONS: Arterial stiffness is higher in pregnant women
with diabetes than in controls. Fetuses of diabetic mothers show altered
cardiovascular parameters, with higher AoV-VTI and lower LV-MPI, which are
markers of myocardial function. Placental function assessed by UA-RI was normal
despite differences between groups. Arterial stiffness did not correlate with
placental or fetal cardiovascular variables. Instead, the findings are likely to
represent a shared response to the environment of abnormal glucose metabolism.
The clinical significance of these findings is yet to be determined. Copyright
(c) 2017 ISUOG. Published by John Wiley & Sons Ltd.
PMID- 28508435
TI - Graphene Oxide Conjugated Magnetic Beads for RNA Extraction.
AB - A magnetic material that consists of silica-coated magnetic beads conjugated with
graphene oxide (GO) was successfully prepared for facile ribonucleic acid (RNA)
extraction. When the GO-modified magnetic beads were applied to separate the RNA
from the lysed cell, the cellular RNAs were readily adsorbed to and readily
desorbed from the surface of the GO-modified magnetic beads by urea. The amount
of RNA extracted by the GO-modified magnetic beads was ~170 % as much as those of
the control extracted by a conventional phenol-based chaotropic solution. These
results demonstrate that the facile method of RNA separation by using GO-modified
magnetic beads as an adsorbent is an efficient and simple way to purify intact
cellular RNAs and/or microRNA from cell lysates.
PMID- 28508436
TI - Bio-functional properties of sardine protein hydrolysates obtained by brewer's
spent yeast and commercial proteases.
AB - BACKGROUND: The canned-sardine industry generates large amounts of protein-rich
waste, which demands useful exploitation. This paper describes the potential use
of muscle and viscera proteins from canned sardine by-products as substrate to
obtain hydrolysates with biological and functional properties. Three enzymatic
approaches, brewer's spent yeast (Bsy) proteases, Alcalase(r) and Neutrase(r)
were applied to perform protein hydrolysis at the same proteolytic activity (1 U
mL-1 ), using an enzyme/substrate ratio of 20% (v/v), at 50 degrees C and for 7
h. Hydrolysis degree (DH), antioxidant and angiotensin I-converting enzyme
inhibitory (ACE-I) activities, functional properties (i.e. solubility,
emulsifying and foaming properties, water and oil binding capacity) and colour
were investigated. RESULTS: All hydrolysates presented a high protein content
[52.7-83.2% dry weight (DW)] and low fat content (0.9-3.9% DW). Alcalase(r)
treatment of muscle and viscera proteins resulted in higher DH (7.5% and 8.6%,
respectively) and higher biological activities (P < 0.05). All hydrolysates had
excellent solubility and presented functional properties. Among viscera
hydrolysates, treatment with Bsy proteases promoted higher emulsion (80.1 m2 g-1
), foaming (79.2%) and oil binding capacity (5.8 g g-1 ) of viscera sardine
proteins. CONCLUSION: Improved biological and functional properties were observed
for sardine protein hydrolysates produced using the three enzymatic treatments
tested. (c) 2017 Society of Chemical Industry.
PMID- 28508437
TI - Characteristics and consequences of falls among older adult trauma patients:
Considerations for injury prevention programs.
AB - BACKGROUND/AIM: Health promotion and prevention is an important component of
occupational therapy practice. Falls are one of the most common causes of ER
visits among older adults and injurious falls requiring trauma care can have a
significant impact on the health and quality of life of elders. The aim of this
study was to compare characteristics and consequences of falls among older adult
trauma patients across different age groups with an eye towards informing injury
prevention programs. METHODS: A retrospective study using the trauma database
from a level one trauma centre in the U.S. (N = 711) was conducted. We compared
patient and fall characteristics across age groups and then used logistic
regression to estimate odds ratios for hospital length of stay >4 days, discharge
disposition, and injury severity (ISS >15). RESULTS: Associations between age
group and fall height, location and alcohol use at the time of the fall were
statistically significant (P < 0.0001). As compared to the reference group (85
and older), younger age groups had lower odds ratios for discharge to a facility
for rehabilitation. CONCLUSION: Results highlight differences among age groups of
fallers admitted for trauma care and can help to inform injury prevention
programs related to outdoor and indoor falls.
PMID- 28508438
TI - The effect of chronotherapy on delirium in critical care - a systematic review.
AB - BACKGROUND: Delirium is highly prevalent within critical care and is linked to
adverse clinical outcomes, increased mortality and impaired quality of life.
Development of delirium is thought to be caused by multiple risk factors,
including disruption of the circadian rhythm. Chronotherapeutic interventions,
such as light therapy, music and use of eye shades, have been suggested as an
option to improve circadian rhythm within intensive care units. AIM: This review
aims to answer the question: Can chronotherapy reduce the prevalence of delirium
in adult patients in critical care? DESIGN: This study is a systematic review of
quantitative studies. RESEARCH METHOD: Six major electronic databases were
searched, and a hand search was undertaken using selected key search terms.
Research quality was assessed using the critical appraisal skills programme
tools. The studies were critically appraised by both authors independently, and
data were extracted. Four themes addressing the research question were identified
and critically evaluated. FINDINGS: Six primary research articles that
investigated different methods of chronotherapy were identified, and the results
suggest that multi-component non-pharmacological interventions are the most
effective for reducing the prevalence of delirium in critical care. The
melatonergic agonist Ramelteon demonstrated statistically significant reductions
in delirium; however, the reliability of the results in answering the review
question was limited by the research design. The use of bright light therapy
(BLT) and dynamic light application had mixed results, with issues with the
research design and outcomes measured limiting the validity of the findings.
CONCLUSION: Multi-component non-pharmacological interventions, such as noise and
light control, can reduce delirium in critical care, whereas other interventions,
such as BLT, have mixed outcomes. Melatonin, as a drug, may be a useful
alternative to sedative-hypnotics. RELEVANCE TO CLINICAL PRACTICE: Chronotherapy
can reduce the incidence of delirium within critical care, although further
research is warranted. Staff education is essential in the implementation of
chronotherapy.
PMID- 28508439
TI - Conventional and right-sided screening for subcutaneous ICD in a population with
congenital heart disease at high risk of sudden cardiac death.
AB - BACKGROUND: Information regarding suitability for subcutaneous defibrillator
(sICD) implantation in tetralogy of Fallot (ToF) and systemic right ventricle is
scarce and needs to be further explored. The main objective of our study was to
determine the proportion of patients with ToF and systemic right ventricle
eligible for sICD with both, standard and right-sided screening methods.
Secondary objectives were: (i) to study sICD eligibility specifically in patients
at high risk of sudden cardiac death, (ii) to identify independent predictors for
sICD eligibility, and (iii) to compare the proportion of eligible patients in a
nonselected ICD population. METHODS: We recruited 102 patients with ToF, 33 with
systemic right ventricle, and 40 consecutive nonselected patients. Conventional
electrocardiographic screening was performed as usual. Right-sided alternative
screening was studied by positioning the left-arm and right-arm electrodes 1 cm
right lateral of the xiphoid midline. The Boston Scientific ECG screening tool
was utilized. RESULTS: In high-risk patients with ToF, eligibility was higher
with right-sided screening in comparison with standard screening (61% vs. 44%; p
= .018). Eligibility in high-risk right ventricle population was identical with
both screening methods (77%, p = ns). The only independent predictor for sICD
eligibility was QRS duration. CONCLUSION: In high-risk patients with ToF, right
sided implantation of the sICD could be an alternative to a conventional ICD. In
patients with a systemic right ventricle, implantation of a sICD is an
alternative to a conventional sICD.
PMID- 28508440
TI - Has evidence-based medicine ever been modern? A Latour-inspired understanding of
a changing EBM.
AB - Evidence-based health care (EBHC), previously evidence-based medicine (EBM), is
considered by many to have modernized health care and brought it from an
authority-based past to a more rationalist, scientific grounding. But recent
concerns and criticisms pose serious challenges and urge us to look at the
fundamentals of a changing EBHC. In this paper, we present French philosopher
Bruno Latour's vision on modernity as a framework to discuss current changes in
the discourse on EBHC/EBM. Drawing on Latour's work, we argue that the early EBM
movement had a strong modernist agenda with an aim to "purify" clinical reality
into a dichotomy of objective "evidence" from nature and subjective "preferences"
from human society and culture. However, we argue that this shift has proved
impossible to achieve in reality. Several recent developments appear to point to
a demise of purified evidence in the EBHC discourse and a growing recognition
albeit implicit and undertheorized-that evidence in clinical decision making is
relentlessly situated and contextual. The unique, individual patient, not
abstracted truths from distant research studies, must be the starting point for
clinical practice. It follows that the EBHC community needs to reconsider the
assumption that science should be abstracted from culture and acknowledge that
knowledge from human culture and nature both need translation and interpretation.
The implications for clinical reasoning are far reaching. We offer some
preliminary principles for conceptualizing EBHC as a "situated practice" rather
than as a sequence of research-driven abstract decisions.
PMID- 28508441
TI - Synthesis of an Aluminum Hydroxide Octamer through a Simple Dissolution Method.
AB - Multimeric oxo-hydroxo Al clusters function as models for common mineral
structures and reactions. Cluster research, however, is often slowed by a lack of
methods to prepare clusters in pure form and in large amounts. Herein, we report
a facile synthesis of the little known cluster Al8 (OH)14 (H2 O)18 (SO4 )5 (Al8 )
through a simple dissolution method. We confirm its structure by single-crystal X
ray diffraction and show by 27 Al NMR spectroscopy, electrospray-ionization mass
spectrometry, and small- and wide-angle X-ray scattering that it also exists in
solution. We speculate that Al8 may form in natural water systems through the
dissolution of aluminum-containing minerals in acidic sulfate solutions, such as
those that could result from acid rain or mine drainage. Additionally, the
dissolution method produces a discrete Al cluster on a scale suitable for studies
and applications in materials science.
PMID- 28508442
TI - Solid-State Gas Adsorption Studies with Discrete Palladium(II) [Pd2 (L)4 ]4+
Cages.
AB - The need for effective CO2 capture systems remains high, and due to their
tunability, metallosupramolecular architectures are an attractive option for gas
sorption. While the use of extended metal organic frameworks for gas adsorption
has been extensively explored, the exploitation of discrete metallocage
architectures to bind gases remains in its infancy. Herein the solid state gas
adsorption properties of a series of [Pd2 (L)4 ]4+ lantern shaped coordination
cages (L = variants of 2,6-bis(pyridin-3-ylethynyl)pyridine), which had solvent
accessible internal cavities suitable for gas binding, have been investigated.
The cages showed little interaction with dinitrogen gas but were able to take up
CO2 . The best performing cage reversibly sorbed 1.4 mol CO2 per mol cage at 298
K, and 2.3 mol CO2 per mol cage at 258 K (1 bar). The enthalpy of binding was
calculated to be 25-35 kJ mol-1 , across the number of equivalents bound, while
DFT calculations on the CO2 binding in the cage gave DeltaE for the cage-CO2
interaction of 23-28 kJ mol-1 , across the same range. DFT modelling suggested
that the binding mode is a hydrogen bond between the carbonyl oxygen of CO2 and
the internally directed hydrogen atoms of the cage.
PMID- 28508443
TI - Stereoselective Synthesis of Tetrasubstituted Alkenes via a Cp*CoIII -Catalyzed C
H Alkenylation/Directing Group Migration Sequence.
AB - A highly atom economical and stereoselective synthesis of tetrasubstituted
alpha,beta-unsaturated amides was achieved by a Cp*CoIII -catalyzed C-H
alkenylation/directing group migration sequence. A carbamoyl directing group,
which is typically removed after C-H functionalization, worked as an internal
acylating agent and migrated onto the alkene moiety of the product. The directing
group migration was realized with the Cp*CoIII catalyst, while a related Cp*RhIII
catalyst did not promote the migration process. The product was further converted
into two types of tricyclic compounds, one of which had fluorescent properties.
PMID- 28508444
TI - Increased adipose tissue expression of IL-18R and its ligand IL-18 associates
with inflammation and insulin resistance in obesity.
AB - INTRODUCTION: The proinflammatory cytokine IL-18 is involved in the pathogenesis
of metabolic syndrome. While the changes in IL-18 are known, IL-18R expression
and relationship with IL-18 and other inflammatory markers in the adipose tissue
in obesity/type-2 diabetes (T2D) remain unclear. METHODS: We, therefore,
determined the adipose tissue expression of IL-18R and IL-18 mRNA/protein in
lean, overweight, and obese individuals with and without T2D, 15 each, using qRT
PCR, immunohistochemistry, and confocal microscopy. Data (mean +/- SEM) were
analyzed using unpaired t-test and Pearson's correlation (r); all P values <=0.05
were considered statistically significant. RESULTS: We found the upregulated
gene/protein expression of IL-18R and IL-18 in non-diabetic obese/overweight as
compared with lean individuals (P < 0.05). BMI correlated positively (P < 0.05)
with the adipose tissue expression of IL-18R (mRNA: r = 0.90 protein: r = 0.84)
and IL-18 (mRNA: r = 0.84 protein: r = 0.80). Similarly, in T2D individuals, gene
and protein expression of IL-18R/IL-18 was significantly higher in obese as
compared with overweight/lean individuals. The BMI was associated with the
changes in both IL-18R (mRNA: r = 0.55 protein: r = 0.50) and IL-18 (mRNA: r =
0.53 protein: r = 0.57) expression. IL-18R/IL-18 gene expression in the adipose
tissue was positively associated (P < 0.05) with local gene expression of other
inflammatory markers including CD11c, CD86, CD68, CD163, TNF-alpha, and CCL5.
Homeostatic model assessment of insulin resistance (HOMA-IR) was higher in
diabetic/non-diabetic obese and it correlated with BMI (P < 0.05). IL-18R and IL
18 mRNA/protein expression in obesity was associated with HOMA-IR only in non
diabetics. CONCLUSIONS: The adipose tissue IL-18R/IL-18 expression is enhanced in
obesity which associates with proinflammatory gene signature and insulin
resistance in these individuals.
PMID- 28508445
TI - Adult height and glucose tolerance: a re-appraisal of the importance of body mass
index.
AB - AIM: To study both the association between adult height and glucose regulation
based on findings from a 75-g oral glucose tolerance test, and the combined
effect of height and adiposity on glucose values. METHODS: We conducted a
population-based, cross-sectional study among apparently healthy people with high
cardiovascular risk living in south-western Finland. The study included 2659
participants aged 45-70 years, who had at least one cardiovascular risk factor
but no previously diagnosed diabetes or manifested cardiovascular disease. An
oral glucose tolerance test was performed in all participants. Height and weight
were measured and BMI was calculated. The participants were divided into five
height groups based on normal distribution. For further analysis of the
association between height and glucose concentrations the participants were
divided into four BMI groups (<25.0 kg/m2 ; 25-29.9 kg/m2 ; 30-34.9 kg/m2 ; >=35
kg/m2 ). Data were analysed using age-adjusted linear regression models. RESULTS:
Height was inversely associated with 2-h plasma glucose, but not with fasting
plasma glucose concentration. No gender difference was observed. The 2-h plasma
glucose values increased with an increase in BMI, so that height was inversely
associated with 2-h plasma glucose in the three lowest BMI groups, but not in the
highest BMI group (P=0.33). CONCLUSIONS: Taller people had lower 2-h plasma
glucose concentrations than shorter people, up to a BMI of 35 kg/m2 . Adjustment
for height and BMI is needed for accurate interpretation of oral glucose
tolerance tests.
PMID- 28508446
TI - Triboluminescence of Lanthanide Coordination Polymers with Face-to-Face Arranged
Substituents.
AB - Luminescence upon the grinding of solid materials (triboluminescence, TL) has
long been a puzzling phenomenon in natural science and has also attracted
attention because of its broad application in optics. It has been generally
considered that the TL spectra exhibit similar profiles as those of
photoluminescence (PL), although they occur from distinct stimuli. Herein, we
describe for the first time a large spectral difference between these two
physical phenomena using lanthanideIII coordination polymers with efficient TL
and PL properties. They are composed of emission centers (TbIII and EuIII ions),
antenna (hexafluoroacetylacetonate=hfa), and bridging ligands (2,5
bis(diphenylphosphoryl)furan=dpf). The emission color upon grinding (yellow TL)
is clearly different from that upon UV irradiation (reddish-orange PL) in TbIII
/EuIII -mixed coordination polymers [Tb,Eu(hfa)3 (dpf)]n (Tb/Eu=1). The results
directly indicate the discrete excitation processes of PL and TL.
PMID- 28508447
TI - The gut-brain connection and the use of probiotics for the treatment of
depression, anxiety and obsessive-compulsive disorders in dermatology.
PMID- 28508448
TI - A novel multi-epitope vaccine from MMSA-1 and DKK1 for multiple myeloma
immunotherapy.
AB - The identification of novel tumour-associated antigens is urgently needed to
improve the efficacy of immunotherapy for multiple myeloma (MM). In this study,
we identified a membrane protein MMSA-1 (multiple myeloma special antigen-1) that
was specifically expressed in MM and exhibited significantly positive correlation
with MM. We then identified HLA-A*0201-restricted MMSA-1 epitopes and tested
their cytotoxic T lymphocyte (CTL) response. The MMSA-1 epitope SLSLLTIYV vaccine
was shown to induce an obvious CTL response in vitro. To improve the
immunotherapy, we constructed a multi-epitope peptide vaccine by combining
epitopes derived from MMSA-1 and Dickkopf-1 (DKK1). The effector T cells induced
by multi-epitope peptide vaccine-loaded dendritic cells lysed U266 cells more
effectively than MMSA-1/DKK1 single-epitope vaccine. In myeloma-bearing severe
combined immunodeficient mice, the multi-epitope vaccine improved the survival
rate significantly compared with single-epitope vaccine. Consistently, multi
epitope vaccine decreased the tumour volume greatly and alleviated bone
destruction. The frequencies of CD4+ and CD8+ T cells was significantly increased
in mouse blood induced by the multi-epitope vaccine, indicating that it inhibits
myeloma growth by changing T cell subsets and alleviating immune paralysis. This
study identified a novel peptide from MMSA-1 and the multi-epitope vaccine will
be used to establish appropriate individualized therapy for MM.
PMID- 28508449
TI - Satellite glial cells in human trigeminal ganglia have a broad expression of
functional Toll-like receptors.
AB - Toll-like receptors (TLRs) orchestrate immune responses to a wide variety of
danger- and pathogen-associated molecular patterns. Compared to the central
nervous system (CNS), expression profile and function of TLRs in the human
peripheral nervous system (PNS) are ill-defined. We analyzed TLR expression of
satellite glial cells (SGCs) and microglia, glial cells predominantly involved in
local immune responses in ganglia of the human PNS and normal-appearing white
matter (NAWM) of the CNS, respectively. Ex vivo flow cytometry analysis of cell
suspensions obtained from human cadaveric trigeminal ganglia (TG) and NAWM showed
that both SGCs and microglia expressed TLR1-5, TLR7, and TLR9, although
expression levels varied between these cell types. Immunohistochemistry confirmed
expression of TLR1-TLR4 and TLR9 by SGCs in situ. Stimulation of TG- and NAWM
derived cell suspensions with ligands of TLR1-TLR6, but not TLR7 and TLR9,
induced interleukin 6 (IL-6) secretion. We identified CD45LOW CD14POS SGCs and
microglia, but not CD45HIGH leukocytes and CD45NEG cells as the main source of IL
6 and TNF-alpha upon stimulation with TLR3 and TLR5 ligands. In conclusion, human
TG-resident SGCs express a broad panel of functional TLRs, suggesting their role
in initiating and orchestrating inflammation to pathogens in human sensory
ganglia.
PMID- 28508450
TI - Simultaneous assessment of both lung morphometry and gas exchange function within
a single breath-hold by hyperpolarized 129 Xe MRI.
AB - During the measurement of hyperpolarized 129 Xe magnetic resonance imaging (MRI),
the diffusion-weighted imaging (DWI) technique provides valuable information for
the assessment of lung morphometry at the alveolar level, whereas the chemical
shift saturation recovery (CSSR) technique can evaluate the gas exchange function
of the lungs. To date, the two techniques have only been performed during
separate breaths. However, the request for multiple breaths increases the cost
and scanning time, limiting clinical application. Moreover, acquisition during
separate breath-holds will increase the measurement error, because of the
inconsistent physiological status of the lungs. Here, we present a new method,
referred to as diffusion-weighted chemical shift saturation recovery (DWCSSR), in
order to perform both DWI and CSSR within a single breath-hold. Compared with
sequential single-breath schemes (namely the 'CSSR + DWI' scheme and the 'DWI +
CSSR' scheme), the DWCSSR scheme is able to significantly shorten the breath-hold
time, as well as to obtain high signal-to-noise ratio (SNR) signals in both DWI
and CSSR data. This scheme enables comprehensive information on lung morphometry
and function to be obtained within a single breath-hold. In vivo experimental
results demonstrate that DWCSSR has great potential for the evaluation and
diagnosis of pulmonary diseases.
PMID- 28508451
TI - Impact of Left Ventricular Diastolic Dysfunction on Lung Transplantation Outcome
in Patients With Pulmonary Arterial Hypertension.
AB - Diastolic dysfunction may influence perioperative outcome, early graft function,
and long-term survival. We compared the outcomes of double lung transplantation
(DLTx) for patients with pulmonary arterial hypertension (PAH) with preoperative
left ventricular (LV) diastolic dysfunction with the outcomes of patients without
diastolic dysfunction. Of 116 consecutive patients with PAH (who underwent
transplantation between January 1995 and December 2013), 44 met our inclusion and
exclusion criteria. Fourteen (31.8%) patients with diastolic dysfunction
pretransplantation had a higher body mass index (29 [IQR 21.5-32.6] vs 22.4 [IQR
19.9-25.3] kg/m2 ) and mean pulmonary arterial pressure (54.6 +/- 10 mmHg vs 47
+/- 11.3 mmHg) and right atrial pressure (16.5 +/- 5.2 mmHg vs 10.6 +/- 5.2
mmHg). The patients received extracorporeal life support more frequently (33% vs
7% [p = 0.02]), had worse APACHE II scores (21.7 +/- 7.4 vs 15.3 +/- 5.3 [p =
0.02]), and a trend toward worse ventilator-free days (2.5 [IQR 6.5-32.5] vs 17
[IQR 3-23] [p = 0.08]). There was no effect on development of primary graft
dysfunction or intensive care unit/hospital survival. One-year survival was worse
(hazard ratio [HR] 4.45, 95% confidence interval [CI] 1.3-22, p = 0.02).
Diastolic dysfunction was the only variable that correlated with overall survival
(HR 5.4, 95% CI 1.3-22, p = 0.02). Diastolic dysfunction leads to early
postoperative morbidity and worse survival in patients with PAH after DLTx.
PMID- 28508452
TI - Mental health cost of terrorism: Study of the Charlie Hebdo attack in Paris.
AB - This study examines whether a terrorist attack in a developed country, which does
not cause major damage to its capital stocks, affects the mental health of its
residents. By exploiting variations in survey dates of the European Social
Survey, we use a difference-in-differences strategy to show that the attack
adversely affects subjective well-being and mental health measures of French
respondents. These negative effects are stronger for immigrants and low-income
individuals. The impact is less dramatic for politically extreme right-wing
supporters. The distance from origin has little impact on these measures.
PMID- 28508453
TI - TetR-dependent gene regulation in intracellular Listeria monocytogenes
demonstrates the spatiotemporal surface distribution of ActA.
AB - To enable specific and tightly controlled gene expression both in vitro and
during the intracellular lifecycle of the pathogen Listeria monocytogenes, a TetR
dependent genetic induction system was developed. Highest concentration of
cytoplasmic TetR and best repression of tetO-controlled genes was obtained by
tetR expression from the synthetic promoter Pt17 . Anhydrotetracycline (ATc) as
inducer permitted concentration-dependent, fine-tuned expression of genes under
control of the tetO operator and a suitable promoter. The actin-polymerizing ActA
protein represents a major virulence factor of L. monocytogenes, required for
actin-based motility and cell-to-cell spread in infected host cells. To be able
to observe its spatial and temporal distribution on intracellular L.
monocytogenes cells, conditional mutants featuring actA placed under TetR control
were used to infect PtK2 epithelial cells. Following induction at different time
intervals, the subsequent recruitment of actin by L. monocytogenes could be
monitored. We found that cells displayed functional ActA after approximately 15
min, while formation of polarized actin tail was complete after 90-120 min. At
this point, intracellular motility of the induced mutants was indistinguishable
from wild-type bacteria. Interestingly, de novo ActA synthesis in intracellular
Listeria also demonstrated the temporal, asymmetric redistribution of the
membrane-anchored proteins from the lateral walls toward the cell poles.
PMID- 28508454
TI - Light-Mediated Reversible Modulation of ROS Level in Living Cells by Using an
Activity-Controllable Nanozyme.
AB - Nanozymes have shown great potential in bioapplications owing to their low cost,
high stability, multiple activity, and biocompatibility. However, most of the
known nanozymes are always at turn-on state, hindering their further
applications. Herein, a simple and versatile method for constructing activity
controllable nanozymes is presented. To the best of our knowledge, this is the
first report to utilize the light-driven isomerization of azobenzene (Azo) and
host-guest interaction to reversibly photoregulating the activity of nanozyme.
Gold nanoparticles as a typical catalase-mimic nanozyme are used in this design.
The expanded Azo-modified mesoporous silica is employed as supported material to
encapsulate and disperse Au nanoparticles, which further combines with
cyclodextrin (CD). The catalytic activity of the nanozyme is blocked by CD and
can be activated or inhibited reversibly by UV or visible light. The results
indicated that the nanozyme can reversibly regulate reactive oxygen species (ROS)
level in extracellular and intracellular environment for multiple cycles and
change cell viability by simply changing the irradiated light. This is a general
method and can be adapted to construct various smart nanozymes with highly
spatiotemporal resolution.
PMID- 28508455
TI - A multicenter real-life study of the efficacy of an alpha-blocker with or without
anticholinergic agent (imidafenacin) treatment in patients with lower urinary
tract symptoms/benign prostatic hyperplasia and storage symptoms.
AB - AIMS: To evaluate the efficacy and safety of combination therapy comprising a
short-acting anticholinergic, imidafenacin and an alpha-blocker compared with
monotherapy with an alpha-blocker only in men with lower urinary tract symptoms
(LUTS) and storage symptoms. METHODS: The 12-week, prospective, double-blind,
randomised trial enrolled men with LUTS and storage symptom. The inclusion
criteria were a total International Prostate Symptom Score (IPSS) >=12, an IPSS
question 4 score >=2, >=8 micturitions in 24 hours, and a prostate volume >20 mL.
The primary outcome was a change in the micturition number from baseline. Bladder
diary variables, Patient Perception of Intensity of Urgency Scale (PPIUS) scores,
IPSS and safety were assessed. RESULTS: Of 260 patients screened, 221 completed
the study. Patients were randomly assigned to receive an alpha-blocker only
(n=111, group 1) or combination therapy comprising an alpha-blocker and an
anticholinergic (n=110, group 2) for 12 weeks. Group 1 and 2 showed significant
improvement in their 24-hour micturition numbers (-1.87 and -2.08, respectively),
nocturia episodes (-0.48 and -0.53, respectively), total IPSS (-9.9 and -8.8,
respectively), and PPIUS scores (-0.19 and -0.24, respectively). Micturition
number per 24 hours, daytime frequency, urgency, the PPIUS score, the IPSS
question 4 score and IPSS QoL score improved significantly in the combination
therapy group, but changes in total IPSS, nocturia episodes, and safety outcomes
did not differ significantly between the groups. CONCLUSIONS AND CLINICAL
IMPLICATIONS: Compared with treatment with an alpha-blocker alone, combination
therapy comprising an anticholinergic and an alpha-blocker showed superior
efficacy and its safety was similar in patients with LUTS and storage symptoms.
PMID- 28508456
TI - Age- and sex-based reference ranges for non-invasive ventricular repolarisation
parameters.
AB - BACKGROUND: Some electrocardiographic parameters are able to assess indirectly
ventricular repolarisation homogeneity. It is consequently essential to
discriminate between normal and abnormal values in clinical decision-making.
Considering there is still not a consensus about normal cut-off values, the aim
of this study was to document reference intervals in all age groups of a healthy
population, providing for age- and sex-percentile tables, which can be used
easily and quickly in clinical practice. METHODS: We evaluated repolarisation
markers in 606 sex-matched participants aged 1 day-94 years. Each subject
underwent a 12-lead electrocardiogram at rest, and the following parameters were
measured: QT, corrected QT, QTpeak, Tpeak-Tend, Tpeak-Tend dispersion, Tpeak
Tend/QT and QTpeak/QT ratio. RESULTS: A relationship was demonstrated between age
and QTpeak, Tpeak-Tend, QT and QTc. In children, QTpeak, Tpeak-Tend and QT
intervals increased linearly with age. In adolescents, all the three parameters
remained stable. In adults, QTpeak and QT showed a further significant increase.
On the contrary, Tpeak-Tend interval was longer in adults aged between 20 and 64
years than in participants aged 65 years or over, but the difference was not
statistically significant. Male vs female participants showed longer Tpeak-Tend
intervals; this sex difference was not statistically significant at birth and
during childhood, whereas it was in adolescents and in adults. CONCLUSIONS:
Repolarisation parameters showed age- and sex-based variations, which are
important to know to differentiate normal from pathological values.
PMID- 28508458
TI - Required reading to remain relevant.
PMID- 28508457
TI - Effects of canagliflozin on cardiovascular risk factors in patients with type 2
diabetes mellitus.
AB - BACKGROUND AND AIMS: Cardiovascular disease is the most common cause of morbidity
and mortality among people with type 2 diabetes mellitus (T2DM). The main
contributors to cardiovascular risk in T2DM are chronic hyperglycaemia, reduced
insulin sensitivity, hypertension and dyslipidaemia. Other cardiovascular risk
factors include obesity and visceral adiposity, increased arterial stiffness and
renal dysfunction. Results from clinical trials, including a long-term
cardiovascular outcome study, have shown that sodium glucose co-transporter 2
(SGLT2) inhibitors can provide multiple cardiometabolic benefits beyond glycaemic
control including inducing mild osmotic diuresis, natriuresis and weight loss.
This review article describes the effects of canagliflozin on cardiovascular risk
factors based on results from its clinical development programme. METHODS: This
review is based on structured searches to identify literature related to the
effects of canagliflozin on cardiovascular risk factors in patients with T2DM.
DISCUSSION AND CONCLUSIONS: Canagliflozin treatment has been shown to provide
glycaemic improvements as well as reductions in blood pressure and body weight
across a broad range of patients with T2DM, including those with elevated
cardiovascular risk. Other observed effects of canagliflozin that may contribute
to improved cardiometabolic outcomes include reduction in uric acid levels,
decreased albuminuria and increases in serum magnesium. Results of ongoing long
term cardiovascular outcomes studies of canagliflozin are expected to provide
additional evidence on the cardiometabolic effects of canagliflozin treatment.
PMID- 28508459
TI - Tailoring pharmacotherapy for male lower urinary tract symptoms: A prospective,
multicenter, observational trial.
AB - OBJECTIVES: The aim of this study was to evaluate the pattern of tailoring and
efficacy of several types of pharmacotherapy in male LUTS. METHODS: Prospectively
404 male subjects were included who were over 40 years old, had at least 3 months
symptom duration, and 12 or higher international prostate symptom score (IPSS).
Subjects were treated with several types of pharmacotherapy for 6 months and were
evaluated with IPSS/QoL at every follow-up. Subjects were subdivided into storage
(44%), nocturia (18.5%), and voiding symptom (37.5%) groups according to the most
bothersome symptom. RESULTS: At 6 months, 188 subjects (46.5%) completed the
study. The mean age was 64.2+/-8.5 years, and symptom duration was 30.6+/-32.6
months. PSA was 2.98+/-7.96 ng/mL, and prostate size was 32.8+/-14.2 cc. IPSS
continually decreased from baseline (18.7) to last follow-up (10.8). Combination
therapy increased from 33.0% to 52.7% at last follow-up (P=.006). However, there
was no difference of IPSS changes between combination and monotherapy groups
(P>.05). Only antimuscarinic prescription significantly increased from 15.4% to
28.2% (P=.004). Mean number of visits to the clinic was 3.6+/-1.3 and the number
of treatment changes was 0.31+/-0.47. The nocturia (0.47+/-0.51) group changed
treatment more than voiding group (0.21+/-0.41, P=.003). However, the voiding
group (-9.4) had significantly more improvement than e storage (-6.4) and
nocturia (-7.8) groups (P=.011). CONCLUSIONS: Male LUTS continually improved over
6 months with customised treatment. Pharmacotherapy for male LUTS should be
tailored by symptom type and alteration of symptoms during treatment.
PMID- 28508460
TI - Treatment patterns and outcomes of Stage IIIB/IIIC melanoma in France, Germany
and the UK: A retrospective and prospective observational study (MELABIS).
AB - AIM: Real-world data on treatment patterns/outcomes in patients with advanced
melanoma, while scarce, are useful for health technology assessments that govern
patient access in many countries. We collected retrospective data on treatment
patterns among patients in France, Germany and the UK with Stage IIIB/IIIC
melanoma with macroscopic lymph node involvement, whose primary melanoma and
regional lymph node metastases had been completely resected. METHODS: Patients
>=18 years were diagnosed between 1 January 2009 and 31 December 2011. Data were
obtained from patients' medical records and a patient survey. RESULTS: Forty-nine
centres provided data on 558 patients: 53.6% had Stage IIIB disease; 58.2% were
of working age (<65 years), 22.5% reported a change in employment status due to
melanoma, 8% were on long-term sick leave; and 35.1% were deceased over the study
period. Overall median distant metastases-free survival was 23.4 months and
median disease-free survival was 13.3 months. Hospitalisation frequency increased
during distant metastatic/terminal disease phases. Adjuvant therapy was received
by 7.0% (14/199) of patients in France, 2.6% (5/195) in the UK, and 33.5%
(55/164) in Germany. Low-dose interferon was used more frequently than other
regimens. High-dose interferon was associated with discontinuation in 28.6% and
dose delay/reduction in 33.3% of patients. CONCLUSIONS: Rapid disease progression
combined with increased use of healthcare resources in later phases of disease
result in a high burden-of-illness for patients and healthcare providers. The use
of adjuvant interferon therapy varies considerably in this population in the
countries studied, highlighting the need for improved treatments for melanoma.
PMID- 28508461
TI - FOXP3 polymorphisms in interstitial lung disease among Chinese Han population: A
genetic association study.
AB - INTRODUCTION: Both genetic and environmental factors are implicated in the
pathogenesis of interstitial lung disease (ILD). Single-nucleotide polymorphisms
(SNPs) in FOXP3 genes were implicated in the causation of some autoimmune
diseases; however, association of these genes and ILD has not been reported.
OBJECTIVES: To investigate whether FOXP3 polymorphisms are associated with ILD in
a representative Chinese population. METHODS: One hundred and fifty-seven ILD
patients and 170 healthy controls were recruited; SNPs were genotyped by the
Sequenom MassARRAY platform and SHEsis was used to estimate the haplotype
frequencies of SNPs. RESULTS: The CC and TC genotypes of FOXP3 rs2280883 were
associated with a significantly higher risk of connective tissue disease
associated ILD (CTP-ILD) than the TT genotype (P = .006). Patients with
idiopathic interstitial pneumonia (IIP) showed a significantly higher frequency
of rs3761547 (GG genotype) and rs3761549 (CC genotype) polymorphisms of FOXP3 as
compared to that in controls (P = .038 and P = .026, respectively). The rs2294021
(TC genotype) was less frequently observed among IIP patients as compared to that
in controls (P = 0.029). In addition, the FOXP3 CAATC haplotype was associated
with a greater risk for CTD-ILD (P =.048) as compared to controls, and the FOXP3
TCCCC haplotype showed an increased IIP risk (P = .001); however, patients with
the FOXP3 TACTT haplotype showed a significant protective effect against IIP (P =
.036). CONCLUSION: FOXP3 polymorphisms may be important markers to determine
susceptibility to IIP or CTP-ILD in Chinese population.
PMID- 28508462
TI - Role of diffusion-weighted imaging in distinguishing thoracoabdominal
neuroblastic tumours of various histological types and differentiation grades.
AB - INTRODUCTION: Diffusion-weighted MR imaging (DWI) has demonstrated a great
potential to help distinguish benign from malignant tumours in paediatric body.
Our purpose is to evaluate whether DWI allow discrimination of thoracoabdominal
neuroblastic tumours of various histological types and differentiation grades.
METHODS: We retrospectively analysed DWI scans of the thoracoabdominal
neuroblastic tumours in 25 children (11 girls, 14 boys). DWI was performed with
two b-values of 0 and 800 s/mm2 on a 3.0T MR scanner. The apparent diffusion
coefficient (ADC) values of different classifications of tumours were compared
with Independent-Samples T Test. RESULTS: In the 25 cases, ganglioneuroma (GN)
was in 3 cases, ganglioneuroblastoma (GNB) in 7 (GNB-Intermixed in 4, GNB-Nodular
in 3) and neuroblastoma (NB) in 15. In three cases of GNB-Nodular, two cases had
poorly differentiated nodules and another had differentiated nodules. In 15 cases
of NB, poorly differentiated, differentiated and undifferentiated tumours were,
respectively, in eight, five and two cases. The ADC value of the NB was
significantly lower than that of GN/GNB (P < 0.001). The ADC of GNB-Nodular/NB
was significantly less than that of GN/GNB-Intermixed (P < 0.0001). In GNB
Nodular/NB detection, there was a cut-off value of 1.165 * 10-3 mm2 /s. In GNB
Nodular/NB, the tumours with poorly differentiated and undifferentiated lesions
(n = 12) had significantly smaller ADC than those with differentiated composition
(n = 6) (P = 0.0012). CONCLUSION: ADC of DWI is highly valuable for
discriminating thoracoabdominal neuroblastic tumours of different histological
types and differentiation grades.
PMID- 28508463
TI - Ovarian high-grade endometrioid stromal sarcoma with YWHAE and NUTM2B
rearrangements.
PMID- 28508464
TI - Arsenic-Rich Polyarsenides Stabilized by Cp*Fe Fragments.
AB - The redox chemistry of [Cp*Fe(eta5 -As5 )] (1, Cp*=eta5 -C5 Me5 ) has been
investigated by cyclic voltammetry, revealing a redox behavior similar to that of
its lighter congener [Cp*Fe(eta5 -P5 )]. However, the subsequent chemical
reduction of 1 by KH led to the formation of a mixture of novel Asn scaffolds
with n up to 18 that are stabilized only by [Cp*Fe] fragments. These include the
arsenic-poor triple-decker complex [K(dme)2 ][{Cp*Fe(MU,eta2:2 -As2 )}2 ] (2) and
the arsenic-rich complexes [K(dme)3 ]2 [(Cp*Fe)2 (MU,eta4:4 -As10 )] (3),
[K(dme)2 ]2 [(Cp*Fe)2 (MU,eta2:2:2:2 -As14 )] (4), and [K(dme)3 ]2 [(Cp*Fe)4 (MU4
,eta4:3:3:2:2:1:1 -As18 )] (5). Compound 4 and the polyarsenide complex 5 are the
largest anionic Asn ligand complexes reported thus far. Complexes 2-5 were
characterized by single-crystal X-ray diffraction, 1 H NMR spectroscopy, EPR
spectroscopy (2), and mass spectrometry. Furthermore, DFT calculations showed
that the intermediate [Cp*Fe(eta5 -As5 )]- , which is presumably formed first,
undergoes fast dimerization to the dianion [(Cp*Fe)2 (MU,eta4:4 -As10 )]2- .
PMID- 28508466
TI - Comparison of the time taken for localised breast surgery pre- and post
introduction of intra-operative digital specimen mammography.
AB - INTRODUCTION: More than half of the patients with an impalpable malignant breast
lesion have a mammographically detected and imaged-guided localisation, which can
be technically challenging for the breast surgeon. Specimen imaging is used to
confirm successful excision of the localised index lesion and has improved the
operating list efficiency resulting in a higher number of excisions per surgical
list. The aim of this study was to evaluate whether introducing IDSM (intra
operative digital specimen mammography) saved operation time for localised breast
surgery. METHODS: A single-centre retrospective review was undertaken to compare
the operation time (from incision to wound closure) taken for excision of 114
consecutive image-guided localised impalpable breast lesions, performed using
departmental specimen radiography (DSR), 6 months prior to the introduction of
IDSM (Hologic, Trident(r) ) in March 2013, with the theatre time taken for
excision of 121 consecutive image-guided localised impalpable breast lesions in
the 6 months following introduction of IDSM. RESULTS: There was no significant
difference in mean surgical time, which were 47.8 (+/-27.3) minutes in the CSR
group and 48.8 (+/-25.7) minutes in the IDSM group. CONCLUSION: We were expecting
to confirm a reduction in theatre time with the introduction of IDSM.
Surprisingly, no difference in operating times was demonstrated. Factors that
influenced the impact of IDSM included the proximity of the imaging department to
the operating theatre.
PMID- 28508467
TI - Keratitis due to microfilariae in dogs: a newly recognized disease.
AB - Parasitic agents have been associated with keratitis, but a diagnosis of
parasitic keratitis has not been commonly made in domestic animals. The purpose
of this study was to describe the clinical and histopathological findings in
seven dogs with chronic keratitis caused by microfilariae diagnosed in Brazil.
All dogs presented with superficial corneal opacities of varying degrees
affecting the perilimbal and central regions of the cornea, with other opaque
areas appearing as crystalline deposits and corneal vascularization. The lesions
were bilateral and were associated with mild-to-moderate conjunctival hyperemia.
There was no history of blepharospasm or pruritus, and no subjects presented with
epithelial erosions. Corneal biopsy revealed free microfilariae in the corneal
stroma, with varying degrees of inflammation and collagen fiber destruction. The
microfilariae were also found in skin lesions by skin snip technique. No adult
worms were found in these dogs, and no dogs were on heartworm preventative before
diagnosis. Monthly doses of oral ivermectin improved ocular and dermal lesions.
One dog showed complete remission with the treatment. The species of the
microfilariae was not identified.
PMID- 28508465
TI - Proteomics show antigen presentation processes in human immune cells after AS03
H5N1 vaccination.
AB - Adjuvants enhance immunity elicited by vaccines through mechanisms that are
poorly understood. Using a systems biology approach, we investigated temporal
protein expression changes in five primary human immune cell populations:
neutrophils, monocytes, natural killer cells, T cells, and B cells after
administration of either an Adjuvant System 03 adjuvanted or unadjuvanted split
virus H5N1 influenza vaccine. Monocytes demonstrated the strongest differential
signal between vaccine groups. On day 3 post-vaccination, several antigen
presentation-related pathways, including MHC class I-mediated antigen processing
and presentation, were enriched in monocytes and neutrophils and expression of
HLA class I proteins was increased in the Adjuvant System 03 group. We identified
several protein families whose proteomic responses predicted seroprotective
antibody responses (>1:40 hemagglutination inhibition titer), including
inflammation and oxidative stress proteins at day 1 as well as immunoproteasome
subunit (PSME1 and PSME2) and HLA class I proteins at day 3 in monocytes. While
comparison between temporal proteomic and transcriptomic results showed little
overlap overall, enrichment of the MHC class I antigen processing and
presentation pathway in monocytes and neutrophils was confirmed by both
approaches.
PMID- 28508468
TI - Photocatalytic Self-Doped SnO2-x Nanocrystals Drive Visible-Light-Responsive
Color Switching.
AB - Visible-light-responsive reversible color-switching systems are attractive to
many applications because visible light has superior penetration and causes far
less damage to organic molecules than UV. Herein, we report that self-doping of
SnO2-x nanocrystals with Sn2+ red-shifts their absorption to the visible region
and simultaneously produces oxygen vacancies, which can effectively scavenge
photogenerated holes and thus enable the color switching of redox dyes using
visible light. Wavelength-selective switching can also be achieved by coupling
the photocatalytic activity of the SnO2-x NCs with the color-switching kinetics
of different redox dyes. The fast light response enables the further fabrication
of a solid film that can be repeatedly written on using a visible laser pen or
projection printing through a photomask. This discovery represents a big step
forward towards practical applications, especially in areas in which safety
issues and photodamage by UV light are of concern.
PMID- 28508469
TI - Defect Chemistry of Nonprecious-Metal Electrocatalysts for Oxygen Reactions.
AB - Oxygen electrocatalysis, including the oxygen-reduction reaction (ORR) and oxygen
evolution reaction (OER), is a critical process for metal-air batteries.
Therefore, the development of electrocatalysts for the OER and the ORR is of
essential importance. Indeed, various advanced electrocatalysts have been
designed for the ORR or the OER; however, the origin of the advanced activity of
oxygen electrocatalysts is still somewhat controversial. The enhanced activity is
usually attributed to the high surface areas, the unique facet structures, the
enhanced conductivities, or even to unclear synergistic effects, but the
importance of the defects, especially the intrinsic defects, is often neglected.
More recently, the important role of defects in oxygen electrocatalysis has been
demonstrated by several groups. To make the defect effect clearer, the recent
development of this concept is reviewed here and a novel principle for the design
of oxygen electrocatalysts is proposed. An overview of the defects in carbon
based, metal-free electrocatalysts for ORR and various defects in metal
oxides/selenides for OER is also provided. The types of defects and controllable
strategies to generate defects in electrocatalysts are presented, along with
techniques to identify the defects. The defect-activity relationship is also
explored by theoretical methods.
PMID- 28508470
TI - Catalytic Asymmetric Inverse-Electron-Demand Hetero-Diels-Alder Reactions.
AB - In this review, the recent developments in catalytic asymmetric inverse-electron
demand hetero-Diels-Alder reaction, which is recognized as one of the most
powerful routes to construct highly functionalized and enantioenriched six
membered heterocycles, are described. The article is organized on the basis of
different kinds of electron-deficient heterodienes, including alpha,beta
unsaturated ketones/aldehydes, o-benzoquinones, alpha,beta-unsaturated imines, N
aryl imines, o-benzoqinone imides, and other aza-olefins.
PMID- 28508471
TI - Needleless emulsion electrospinning for the regulated delivery of susceptible
proteins.
AB - In the present work, we developed a novel needleless emulsion electrospinning
technique that improves the production rate of the core/shell production process.
The nanofibres are based on poly-epsilon-caprolactone (PCL) as a continuous phase
combined with a droplet phase based on Pluronic F-68 (PF-68). The PCL-PF-68
nanofibres show a time-regulated release of active molecules. Needleless emulsion
electrospinning was used to encapsulate a diverse set of compounds to the core
phase [i.e. 5-(4,6-dichlorotriazinyl) aminofluorescein -PF-68, horseradish
peroxidase, Tetramethylrhodamine-dextran, insulin growth factor-I, transforming
growth factor-beta and basic fibroblast growth factor]. In addition, the PF-68
facilitates the preservation of the bioactivity of delivered proteins. The
system's potential was highlighted by an improvement in the metabolic activity
and proliferation of mesenchymal stem cells. The developed system has the
potential to deliver susceptible molecules in tissue-engineering applications.
PMID- 28508472
TI - Fatal Ingestion of Chlumsky Disinfectant Solution.
AB - A 32-year-old pregnant woman in the 25th week of pregnancy underwent oral glucose
tolerance screening at the diabetologist's. Later that day, she was found dead in
her apartment possibly poisoned with Chlumsky disinfectant solution (solutio
phenoli camphorata). An autopsy revealed chemical burns in the digestive system.
The lungs and the brain showed signs of severe edema. The blood of the woman and
fetus was analyzed using gas chromatography with mass spectrometry and revealed
phenol, its metabolites (phenyl glucuronide and phenyl sulfate) and camphor. No
ethanol was found in the blood samples. Both phenol and camphor are contained in
Chlumsky disinfectant solution, which is used for disinfecting surgical equipment
in healthcare facilities. Further investigation revealed that the deceased woman
had been accidentally administered a disinfectant instead of a glucose solution
by the nurse, which resulted in acute intoxication followed by the death of the
pregnant woman and the fetus.
PMID- 28508473
TI - Vertical Charge Transport via Small Polaron Hopping within TIPS-Pentacene
Lamellar Single Crystal.
AB - A modified liquid method is employed to grow an ultralarge 6,13
bis(triisopropylsilylethynyl)pentacene crystal, ensuring fabrication and
measurements of the two terminal devices. The hole transport mechanism is studied
by analyzing the space charge limited currents (SCLCs) at various temperatures.
Modified SCLC theory with a small polaron hopping model is developed and employed
to successfully simulate the I-V curves. Values of effective hopping distance,
transfer integral, and reorganization energy are extracted and reasonably
discussed. A scenario is suggested that hopping transport takes place from one
molecule to its nearest neighbor along the c-axis, with every molecule acting as
a trapping center.
PMID- 28508474
TI - Interrogation of a PS1-Based Photocathode by Means of Scanning
Photoelectrochemical Microscopy.
AB - In the development of photosystem-based energy conversion devices, the in-depth
understanding of electron transfer processes involved in photocurrent generation
and possible charge recombination is essential as a basis for the development of
photo-bioelectrochemical architectures with increased efficiency. The evaluation
of a bio-photocathode based on photosystem 1 (PS1) integrated within a redox
hydrogel by means of scanning photoelectrochemical microscopy (SPECM) is
reported. The redox polymer acts as a conducting matrix for the transfer of
electrons from the electrode surface to the photo-oxidized P700 centers within
PS1, while methyl viologen is used as charge carrier for the collection of
electrons at the reduced FB site of PS1. The analysis of the modified surfaces by
SPECM enables the evaluation of electron-transfer processes by simultaneously
monitoring photocurrent generation at the bio-photoelectrode and the associated
generation of reduced charge carriers. The possibility to visualize charge
recombination processes is illustrated by using two different electrode
materials, namely Au and p-doped Si, exhibiting substantially different electron
transfer kinetics for the reoxidation of the methyl viologen radical cation used
as freely diffusing charge carrier. In the case of p-doped Si, a slower
recombination kinetics allows visualization of methyl viologen radical cation
concentration profiles from SPECM approach curves.
PMID- 28508475
TI - Functional properties of peripheral CD8+ T cells in patients with repeated
implantation failure.
AB - CD8+ T cells are the main candidates to recognize and respond to fetal HLA-C at
the fetal-maternal interface, but data on the amount of peripheral CD8+ T cells
and their functions during the window of implantation in recurrent implantation
failure (RIF) patients are limited. Peripheral blood was obtained from 56 women
with RIF and 16 fertile women in the mid-luteal phase of the menstrual cycle, and
the CD8+ T cells were determined by FACS analysis. No statistical differences in
the proportion of peripheral CD8+ T cells were observed among the women with RIF
and the control group. However, the levels of IFN-gamma+ and TNF-alpha+ CD8+ T
cells in the RIF group were significantly higher than those in the control group.
The cytolytic activity and regulatory proportion of CD8+ T cells in RIF were
similar to that in the control group. Our data indicated that the elevated
expression levels of IFN-gamma and TNF-alpha in peripheral CD8+ T cells may
contribute to an impaired immune tolerance in women with RIF.
PMID- 28508476
TI - Magnetic resonance electrical properties tomography for small anomalies using
boundary conditions: A simulation study.
AB - PURPOSE: Magnetic resonance electrical property tomography (MREPT) is an emerging
imaging modality using measured B1 maps from magnetic resonance imaging (MRI) to
measure a distribution of electric conductivity and permittivity of the subject
at the Larmor frequency. Conventional MREPT approaches at single transmit channel
system using the Helmholtz equation rely on an assumption that conductivity and
permittivity of the subject are locally homogeneous. For small tissue structures
and tissue boundaries, in which the assumption of locally homogeneous
conductivity and permittivity does not hold, the reconstructed conductivity
values deviated from the actual values, so called "Boundary Artifacts." The aim
of this study is to propose new reconstruction processes based on time-harmonic
Maxwell's equations to reconstruct conductivity for small tissue structures and
tissue boundaries. METHODS: Instead of removing the electric fields from the
equations as done in the Helmholtz equation, three key identities of circularly
polarized and longitudinal components of electric fields, circularly polarized
component of magnetic fields, and electric properties from time-harmonic
Maxwell's equations are derived. Based on the three key identities, the proposed
reconstruction methods determine conductivity, permittivity, and circularly
polarized component and longitudinal component of electric fields using the
measured H1+ . In each iterative step, estimated conductivity, permittivity,
electric fields, and artifact-free mask region, Omega, where the contribution of
the boundary artifacts is small, were updated. Using the estimated values in the
artifact-free mask region as boundary conditions, the estimates beyond the mask
region were updated. EM simulations were performed on three types of numerical
phantoms with very small regions of homogeneous conductivity and permittivity.
The performance of the proposed methods was evaluated using the simulated
electric and magnetic fields. RESULTS: For the numerical simulation model, the
proposed methods significantly reduced the boundary artifacts compared to
conventional methods using Helmholtz equations. In addition, previous methods
using the Helmholtz equation could measure conductivity of only large anomalies,
but the proposed method can measure the conductivity of the small compartments
whose size is 2-3 voxels. The proposed approaches are compatible with spatial
filtering which can be used to reduce noise. If a good image segmentation is
available as a prior information, better initial boundary conditions can be
estimated, and thus the proposed approach can be more accurate for small tissue
structures. CONCLUSIONS: The proposed reconstruction method not only determines
electrical properties, but also circularly polarized component and longitudinal
component of electric fields using an iterative process. The proposed method can
quantitatively detect the conductivity of the small anomalies better than
conventional methods.
PMID- 28508477
TI - The novel intracellular protein CREG inhibits hepatic steatosis, obesity, and
insulin resistance.
AB - : Cellular repressor of E1A-stimulated genes (CREG), a novel cellular
glycoprotein, has been identified as a suppressor of various cardiovascular
diseases because of its capacity to reduce hyperplasia, maintain vascular
homeostasis, and promote endothelial restoration. However, the effects and
mechanism of CREG in metabolic disorder and hepatic steatosis remain unknown.
Here, we report that hepatocyte-specific CREG deletion dramatically exacerbates
high-fat diet and leptin deficiency-induced (ob/ob) adverse effects such as
obesity, hepatic steatosis, and metabolic disorders, whereas a beneficial effect
is conferred by CREG overexpression. Additional experiments demonstrated that c
Jun N-terminal kinase 1 (JNK1) but not JNK2 is largely responsible for the
protective effect of CREG on the aforementioned pathologies. Notably, JNK1
inhibition strongly prevents the adverse effects of CREG deletion on steatosis
and related metabolic disorders. Mechanistically, CREG interacts directly with
apoptosis signal-regulating kinase 1 (ASK1) and inhibits its phosphorylation,
thereby blocking the downstream MKK4/7-JNK1 signaling pathway and leading to
significantly alleviated obesity, insulin resistance, and hepatic steatosis.
Importantly, dramatically reduced CREG expression and hyperactivated JNK1
signaling was observed in the livers of nonalcoholic fatty liver disease (NAFLD)
patients, suggesting that CREG might be a promising therapeutic target for NAFLD
and related metabolic diseases. CONCLUSION: The results of our study provides
evidence that CREG is a robust suppressor of hepatic steatosis and metabolic
disorders through its direct interaction with ASK1 and the resultant inactivation
of ASK1-JNK1 signaling. This study offers insights into NAFLD pathogenesis and
its complicated pathologies, such as obesity and insulin resistance, and paves
the way for disease treatment through targeting CREG. (Hepatology 2017;66:834
854).
PMID- 28508478
TI - Accuracy of genomic within-family selection in aquaculture breeding programmes.
AB - In aquaculture breeding programmes, selection within families cannot be applied
for traits that cannot be recorded on the candidates (e.g., disease resistance or
fillet quality). However, this problem can be overcome if genomic evaluation is
used. Within-family genomic evaluation has been proposed for these programmes as
large family sizes are available and substantial levels of linkage disequilibrium
(LD) within families can be attained with a limited number of markers even in
populations in global linkage equilibrium. Here, we compare by computer
simulation: (i) within-family and population-wide LD; and (ii) the accuracy of
within-family genomic selection when genomic evaluations are carried out either
at the population level or within families. The population simulated was composed
by a varying number of families of full-sibs (half for training and half for
testing). The results indicate that, to practice within-family selection,
performing the genomic evaluation separately for each family using only molecular
information from the family could be recommended for populations either in
linkage equilibrium or with a low level of disequilibrium.
PMID- 28508479
TI - Prediction of complex traits: Conciliating genetics and statistics.
AB - This review focuses on methods used to predict complex traits. Main
characteristics of prediction approaches are given: the deterministic or
stochastic nature of prediction, the objects of prediction, the sources of
information and the main statistical methods. Sources of information discussed
are the traditional genealogies and phenotypes, nucleotide sequences, expression
data and epigenetics marks. Statistical methods are presented as successive
degrees of generalization from the definition of the conditional expectation as
the prediction rule, to best linear unbiased prediction, then Bayesian and,
recently, machine learning methods, including meta-methods. We highlight the
contributions of Daniel Gianola to this methodological evolution.
PMID- 28508481
TI - A comparison of identity-by-descent and identity-by-state matrices that are used
for genetic evaluation and estimation of variance components.
AB - The genetic covariance matrix conditional on pedigree is proportional to the
pedigree-based additive relationship matrix (PARM), which is twice the matrix of
identity-by-descent (IBD) probabilities. In genomic prediction, IBD probabilities
in the PARM, which are expected genetic similarities between relatives that are
derived from the pedigree, are substituted by realized similarities that are
derived from genotypes to obtain a genomic additive relationship matrix (GARM).
Different definitions of similarity lead to different GARMs, and two commonly
used GARMS are the matrix G, which is based on an allele substitution effect
model, and the matrix T, which is based on an allele effect model. We show that
although the two matrices T and G are not proportional, they give identical
predictions of differences between breeding values. When genomic information is
used for variance component estimation, the GARM Gx is computed from genotype
covariates that have been standardized to have unit variance. That approach is
equivalent to fitting a random regression model using the same standardized
covariates. We show that under Hardy-Weinberg and linkage equilibria (LE) that
the genetic variance is ksigmagamma2, where sigmagamma2 is the variance of a
randomly sampled element from the vector of k substitution effects. However, if
linkage disequilibrium (LD) has been generated through selection, covariances
between genotypes at different loci will be negative, and therefore, the additive
genetic variance will be lower than ksigmagamma2. When the GARM Gx is assumed to
be proportional to the genetic covariance matrix, the parameter being estimated
is ksigmagamma2. We have demonstrated by simulation that ksigmagamma2
overestimates the additive genetic variance when LD is generated by selection. We
argue that unlike the PARM, GARMs are not proportional to a genetic covariance
matrix conditional on the observed causal genotypes. The objective here is to
recognize the difference between these covariance matrices and its implications.
PMID- 28508480
TI - Beyond genomic selection: The animal model strikes back (one generation)!
AB - Genome inheritance is by segments of DNA rather than by independent loci. We
introduce the ancestral regression (AR) as a recursive system of simultaneous
equations, with grandparental path coefficients as novel parameters. The
information given by the pedigree in the AR is complementary with that provided
by a dense set of genomic markers, such that the resulting linear function of
grandparental BV is uncorrelated to the average of parental BV in the absence of
inbreeding. AR is then connected to segmental inheritance by a causal
multivariate Gaussian density for BV. The resulting covariance structure (Sigma)
is Markovian, meaning that conditional on the BV of parents and grandparents, the
BV of the animal is independent of everything else. Thus, an algorithm is
presented to invert the resulting covariance structure, with a computing effort
that is linear in the number of animals as in the case of the inverse additive
relationship matrix.
PMID- 28508482
TI - Solving efficiently large single-step genomic best linear unbiased prediction
models.
AB - Single-step genomic BLUP (ssGBLUP) requires a dense matrix of the size equal to
the number of genotyped animals in the coefficient matrix of mixed model
equations (MME). When the number of genotyped animals is high, solving time of
MME will be dominated by this matrix. The matrix is the difference of two inverse
relationship matrices: genomic (G) and pedigree (A22 ). Different approaches were
used to ease computations, reduce computing time and improve numerical stability.
Inverse of A22 can be computed as A22-1=A22-A21A11-1A12 where Aij , i, j = 1,2,
are sparse sub-matrices of A-1 , and numbers 1 and 2 refer to non-genotyped and
genotyped animals, respectively. Inversion of A11 was avoided by three
alternative approaches: iteration on pedigree (IOP), matrix iteration in memory
(IM), and Cholesky decomposition by CHOLMOD library (CM). For the inverse of G,
the APY (algorithm for proven and young) approach using Cholesky decomposition
was formulated. Different approaches to choose the APY core were compared. These
approaches were tested on a joint genetic evaluation of the Nordic Holstein
cattle for fertility traits and had 81,031 genotyped animals. Computing time per
iteration was 1.19 min by regular ssGBLUP, 1.49 min by IOP, 1.32 min by IM, and
1.21 min by CM. In comparison with the regular ssGBLUP, the total computing time
decreased due to omitting the inversion of the relationship matrix A22 . When APY
used 10,000 (20,000) animals in the core, the computing time per iteration was at
most 0.44 (0.63) min by all the APY alternatives. A core of 10,000 animals in APY
gave GEBVs sufficiently close to those by regular ssGBLUP but needed only 25% of
the total computing time. The developed approaches to invert the two relationship
matrices are expected to allow much higher number of genotyped animals than was
used in this study.
PMID- 28508483
TI - Genomic variance estimates: With or without disequilibrium covariances?
AB - Whole-genome regression methods are often used for estimating genomic
heritability: the proportion of phenotypic variance that can be explained by
regression on marker genotypes. Recently, there has been an intensive debate on
whether and how to account for the contribution of linkage disequilibrium (LD) to
genomic variance. Here, we investigate two different methods for genomic variance
estimation that differ in their ability to account for LD. By analysing flowering
time in a data set on 1,057 fully sequenced Arabidopsis lines with strong
evidence for diversifying selection, we observed a large contribution of
covariances between quantitative trait loci (QTL) to the genomic variance. The
classical estimate of genomic variance that ignores covariances underestimated
the genomic variance in the data. The second method accounts for LD explicitly
and leads to genomic variance estimates that when added to error variance
estimates match the sample variance of phenotypes. This method also allows
estimating the covariance between sets of markers when partitioning the genome
into subunits. Large covariance estimates between the five Arabidopsis
chromosomes indicated that the population structure in the data led to strong LD
also between physically unlinked QTL. By consecutively removing population
structure from the phenotypic variance using principal component analysis, we
show how population structure affects the magnitude of LD contribution and the
genomic variance estimates obtained with the two methods.
PMID- 28508484
TI - Special Issue: Quantitative and statistical genetics-papers in honour of Daniel
Gianola.
PMID- 28508485
TI - "Conversion" of epistatic into additive genetic variance in finite populations
and possible impact on long-term selection response.
AB - The role of epistasis in understanding the genetic architecture and variation of
quantitative traits and its role, if any, in artificial selection and livestock
improvement more generally has a long and sometimes controversial history. Its
presence has been clearly demonstrated in, for example, laboratory experiments,
but the amount of variation it contributes is likely to be small in outbred
populations. In a finite population, although additive x additive epistatic
variance is lost by genetic drift, it also contributes by conversion to additive
variance through drift sampling and therefore has a potential indirect role in
medium and long-term selection response, with superficial similarity to and hard
to distinguish from mutation. Whilst predictions of response require knowledge of
genetic parameters, an infinitesimal model provides some analytic results.
Otherwise there is little quantitative information relevant to animal populations
on which to judge this potential role of epistasis and reach firm conclusions.
PMID- 28508486
TI - Pedigree-based estimation of covariance between dominance deviations and additive
genetic effects in closed rabbit lines considering inbreeding and using a
computationally simpler equivalent model.
AB - Inbreeding generates covariances between additive and dominance effects (breeding
values and dominance deviations). In this work, we developed and applied models
for estimation of dominance and additive genetic variances and their covariance,
a model that we call "full dominance," from pedigree and phenotypic data.
Estimates with this model such as presented here are very scarce both in
livestock and in wild genetics. First, we estimated pedigree-based condensed
probabilities of identity using recursion. Second, we developed an equivalent
linear model in which variance components can be estimated using closed-form
algorithms such as REML or Gibbs sampling and existing software. Third, we
present a new method to refer the estimated variance components to meaningful
parameters in a particular population, i.e., final partially inbred generations
as opposed to outbred base populations. We applied these developments to three
closed rabbit lines (A, V and H) selected for number of weaned at the Polytechnic
University of Valencia. Pedigree and phenotypes are complete and span 43, 39 and
14 generations, respectively. Estimates of broad-sense heritability are 0.07,
0.07 and 0.05 at the base versus 0.07, 0.07 and 0.09 in the final generations.
Narrow-sense heritability estimates are 0.06, 0.06 and 0.02 at the base versus
0.04, 0.04 and 0.01 at the final generations. There is also a reduction in the
genotypic variance due to the negative additive-dominance correlation. Thus, the
contribution of dominance variation is fairly large and increases with inbreeding
and (over)compensates for the loss in additive variation. In addition, estimates
of the additive-dominance correlation are -0.37, -0.31 and 0.00, in agreement
with the few published estimates and theoretical considerations.
PMID- 28508487
TI - Accuracy of genomic breeding values revisited: Assessment of two established
approaches and a novel one to determine the accuracy in two-step genomic
prediction.
AB - Selection decisions in genomic selection schemes are made based on genomic
breeding values (GBV) of candidates. Thus, the accuracy of GBV is a relevant
parameter, as it reflects the stability of prediction and the possibility that
the GBV might change when more information becomes available. Accuracy of genomic
prediction defined as the correlation between GBV and true breeding values (TBV),
however, is difficult to assess, considering TBV of the candidates are not
available in reality. In previous studies, several methods were proposed to
assess the accuracy of GBV including methods using population parameters or
parameters inferred from mixed-model equations. In practice, most approaches
tended to overestimate the accuracy of genomic prediction. We thus tested
approaches used in previous studies in order to assess the magnitude of bias.
Analyses were performed based on simulated data under a variety of scenarios
mimicking different livestock breeding programmes. Furthermore, we proposed a
novel method and tested it both with simulated data and in a real Holstein data
set. The new method provided a better prediction for the accuracy of GBV in the
simulated scenarios.
PMID- 28508488
TI - Modelling female fertility traits in beef cattle using linear and non-linear
models.
AB - Female fertility traits are key components of the profitability of beef cattle
production. However, these traits are difficult and expensive to measure,
particularly under extensive pastoral conditions, and consequently, fertility
records are in general scarce and somehow incomplete. Moreover, fertility traits
are usually dominated by the effects of herd-year environment, and it is
generally assumed that relatively small margins are kept for genetic improvement.
New ways of modelling genetic variation in these traits are needed. Inspired in
the methodological developments made by Prof. Daniel Gianola and co-workers, we
assayed linear (Gaussian), Poisson, probit (threshold), censored Poisson and
censored Gaussian models to three different kinds of endpoints, namely calving
success (CS), number of days from first calving (CD) and number of failed oestrus
(FE). For models involving FE and CS, non-linear models overperformed their
linear counterparts. For models derived from CD, linear versions displayed better
adjustment than the non-linear counterparts. Non-linear models showed
consistently higher estimates of heritability and repeatability in all cases (h2
< 0.08 and r < 0.13, for linear models; h2 > 0.23 and r > 0.24, for non-linear
models). While additive and permanent environment effects showed highly
favourable correlations between all models (>0.789), consistency in selecting the
10% best sires showed important differences, mainly amongst the considered
endpoints (FE, CS and CD). In consequence, endpoints should be considered as
modelling different underlying genetic effects, with linear models more
appropriate to describe CD and non-linear models better for FE and CS.
PMID- 28508489
TI - Prediction of whole-genome risk for selection and management of hyperketonemia in
Holstein dairy cattle.
AB - Hyperketonemia (HYK), a common early postpartum health disorder characterized by
elevated blood concentrations of beta-hydroxybutyrate (BHB), affects millions of
dairy cows worldwide and leads to significant economic losses and animal welfare
concerns. In this study, blood concentrations of BHB were assessed for 1,453
Holstein cows using electronic handheld meters at four time points between 5 and
18 days postpartum. Incidence rates of subclinical (1.2 <= maximum BHB <= 2.9
mmol/L) and clinical ketosis (maximum BHB >= 3.0 mmol/L) were 24.0 and 2.4%,
respectively. Variance components, estimated breeding values, and predicted HYK
phenotypes were computed on the original, square-root, and binary scales.
Heritability estimates for HYK ranged from 0.058 to 0.072 in pedigree-based
analyses, as compared to estimates that ranged from 0.071 to 0.093 when pedigrees
were augmented with 60,671 single nucleotide polymorphism genotypes of 959 cows
and 801 male ancestors. On average, predicted HYK phenotypes from the genome
enhanced analysis ranged from 0.55 mmol/L for first-parity cows in the best
contemporary group to 1.40 mmol/L for fourth-parity cows in the worst
contemporary group. Genome-enhanced predictions of HYK phenotypes were more
closely associated with actual phenotypes than pedigree-based predictions in five
fold cross-validation, and transforming phenotypes to reduce skewness and
kurtosis also improved predictive ability. This study demonstrates the
feasibility of using repeated cowside measurement of blood BHB concentration in
early lactation to construct a reference population that can be used to estimate
HYK breeding values for genomic selection programmes and predict HYK phenotypes
for genome-guided management decisions.
PMID- 28508490
TI - Divergent Synthesis of Disulfanes and Benzenesulfonothioates Bearing 2
Aminofurans From N-Tosylhydrazone-Bearing Thiocarbamates.
AB - An efficient and convenient synthesis of valuable disulfanes and
benzenesulfonothioates, having a 2-aminofuran framework, has been developed by
employing a copper-catalyzed transformation of readily available N-tosylhydrazone
bearing thiocarbamates. This method features an inexpensive metal catalyst, mild
reaction conditions, good functional-group tolerance, short reaction times, and
delivers valuable and complex products. A copper carbene generated from an N
tosylhydrazone-bearing thiocarbamate is proposed as the key intermediate for the
transformation and it triggers the subsequent cascade. Remarkably, the Ts anion
released from N-tosylhydrazone further serves as a nucleophile, thus rendering
the formation of benzenesulfonothioates under controlled conditions.
PMID- 28508491
TI - Implementation of absolute quantification in small-animal SPECT imaging: Phantom
and animal studies.
AB - PURPOSE: Presence of photon attenuation severely challenges quantitative accuracy
in single-photon emission computed tomography (SPECT) imaging. Subsequently,
various attenuation correction methods have been developed to compensate for this
degradation. The present study aims to implement an attenuation correction method
and then to evaluate quantification accuracy of attenuation correction in small
animal SPECT imaging. METHODS: Images were reconstructed using an iterative
reconstruction method based on the maximum-likelihood expectation maximization
(MLEM) algorithm including resolution recovery. This was implemented in our
designed dedicated small-animal SPECT (HiReSPECT) system. For accurate
quantification, the voxel values were converted to activity concentration via a
calculated calibration factor. An attenuation correction algorithm was developed
based on the first-order Chang's method. Both phantom study and experimental
measurements with four rats were used in order to validate the proposed method.
RESULTS: The phantom experiments showed that the error of -15.5% in the
estimation of activity concentration in a uniform region was reduced to +5.1%
when attenuation correction was applied. For in vivo studies, the average
quantitative error of -22.8 +/- 6.3% (ranging from -31.2% to -14.8%) in the
uncorrected images was reduced to +3.5 +/- 6.7% (ranging from -6.7 to +9.8%)
after applying attenuation correction. CONCLUSION: The results indicate that the
proposed attenuation correction algorithm based on the first-order Chang's
method, as implemented in our dedicated small-animal SPECT system, significantly
improves accuracy of the quantitative analysis as well as the absolute
quantification.
PMID- 28508492
TI - Comparison of vertical and horizontal swimming behaviour of the weather loach
Misgurnus anguillicaudatus.
AB - Experiments on the swimming kinetics and behaviour of weather loach Misgurnus
anguillicaudatus showed that horizontal swim speed was significantly greater than
swim speeds when ascending to or descending from the water surface to gulp air.
Vertical swimming speeds during ascending or descending were similar. Misgurnus
anguillicaudatus swam unsteadily during vertical movements compared with
horizontal movements.
PMID- 28508495
TI - What is the best imaging technique in discriminating dementia with Lewy bodies
from other dementias?
PMID- 28508494
TI - High-dose prednisolone after intravenous methylprednisolone improves prognosis of
acute exacerbation in idiopathic interstitial pneumonias.
AB - BACKGROUND AND OBJECTIVE: Acute exacerbation (AE) of idiopathic pulmonary
fibrosis (IPF) (AE-IPF) is a poor prognostic disorder. AE is also reported to
occur in other idiopathic interstitial pneumonias (IIPs). There are limited data
available regarding the effectiveness of treatment for AE-IIPs. The objective of
this study was to clarify the prognostic impact of the initial dose of
prednisolone (PSL) for treating AE-IIPs. METHODS: Eighty-five patients with AE
IIPs, diagnosed according to the criteria of the Japanese Respiratory Society,
were enrolled in this study (IPF/non-IPF: 63/22 patients) from 2004 to 2013. We
performed multivariate Cox proportional hazard regression analysis to identify
poor prognostic factors. HRCT patterns at the onset of AE-IIPs were classified as
diffuse or non-diffuse. We evaluated the prognostic significance of the initial
dose of PSL by adjusting for other prognostic factors. RESULTS: Median survival
time (MST) after AE-IIPs diagnosis was 49 days. MST of AE-IPF and AE-non-IPF was
39 and 49 days, respectively. A diffuse HRCT pattern, lower serum IgG and higher
serum surfactant protein-D at AE diagnosis, long-term oxygen therapy (LTOT)
before AE and positive pressure ventilation (PPV) use for AE were significant
poor prognostic factors for all patients, as were LTOT before AE and lower serum
IgG for no-PPV patients. High-dose PSL >= 0.6 mg/kg was a significant prognostic
factor for no-PPV patients after adjusting for other prognostic factors.
CONCLUSION: We concluded that a dose of PSL >= 0.6 mg/kg after i.v. high-dose
methylprednisolone therapy should be recommended for the treatment of AE-IIPs.
PMID- 28508496
TI - Effect of sex on the association of isokinetic quadriceps strength with
hypertension among older Americans.
PMID- 28508493
TI - Exome sequencing reveals novel genetic loci influencing obesity-related traits in
Hispanic children.
AB - OBJECTIVE: To perform whole exome sequencing in 928 Hispanic children and
identify variants and genes associated with childhood obesity. METHODS: Single
nucleotide variants (SNVs) were identified from Illumina whole exome sequencing
data using integrated read mapping, variant calling, and an annotation pipeline
(Mercury). Association analyses of 74 obesity-related traits and exonic variants
were performed using SeqMeta software. Rare autosomal variants were analyzed
using gene-based association analyses, and common autosomal variants were
analyzed at the SNV level. RESULTS: (1) Rare exonic variants in 10 genes and 16
common SNVs in 11 genes that were associated with obesity traits in a cohort of
Hispanic children were identified, (2) novel rare variants in peroxisome
biogenesis factor 1 (PEX1) associated with several obesity traits (weight, weight
z score, BMI, BMI z score, waist circumference, fat mass, trunk fat mass) were
discovered, and (3) previously reported SNVs associated with childhood obesity
were replicated. CONCLUSIONS: Convergence of whole exome sequencing, a family
based design, and extensive phenotyping discovered novel rare and common variants
associated with childhood obesity. Linking PEX1 to obesity phenotypes poses a
novel mechanism of peroxisomal biogenesis and metabolism underlying the
development of childhood obesity.
PMID- 28508497
TI - Personality traits and behavioral disturbances in dementia: A new risk factor?
PMID- 28508498
TI - Femoral osteoporosis is more common than lumbar osteoporosis in patients with
Werner syndrome.
PMID- 28508499
TI - Author's reply "What is the best neuroimaging technique in discriminating
dementia with Lewy bodies from Alzheimer's disease?"
PMID- 28508500
TI - Hyponatremia after initiation of angiotensin-converting enzyme inhibitor in a
geriatric patient with chronic heart failure: A case of mineralocorticoid
responsive hyponatremia of the elderly.
PMID- 28508501
TI - Case of insulinoma manifesting as hyperinsulinemia after discontinuing quetiapine
in an elderly patient with delirium.
PMID- 28508502
TI - Reduced brain-derived neurotrophic factor is associated with cognitive
dysfunction in patients with chronic heart failure.
PMID- 28508504
TI - AibA/AibB Induces an Intramolecular Decarboxylation in Isovalerate Biosynthesis
by Myxococcus xanthus.
AB - Isovaleryl coenzyme A (IV-CoA) is an important precursor for iso-fatty acids and
lipids. It acts in the development of myxobacteria, which can produce this
compound from acetyl-CoA through alternative IV-CoA biosynthesis (aib). A central
reaction of aib is catalyzed by AibA/AibB, which acts as a cofactor-free
decarboxylase despite belonging to the family of CoA-transferases. We developed
an efficient expression system for AibA/AibB that allowed the determination of
high-resolution crystal structures in complex with different ligands. Through
mutational studies, we show that an active-site cysteine previously proposed to
be involved in decarboxylation is not required for activity. Instead, AibA/AibB
seems to induce an intramolecular decarboxylation by binding its substrate in a
hydrophobic cavity and forcing it into a bent conformation. Our study opens
opportunities for synthetic biology studies, since AibA/AibB may be suitable for
the production of isobutene, a precursor of biofuels and chemicals.
PMID- 28508503
TI - Expanding analytical options in sports drug testing: Mass spectrometric detection
of prohibited substances in exhaled breath.
AB - RATIONALE: Continuously refining and advancing the strategies and methods
employed in sports drug testing is critical for efficient doping controls.
Besides improving and expanding the spectrum of target analytes, alternative test
matrices have warranted in-depth evaluation as they commonly allow for minimal
/non-invasive and non-intrusive sample collection. In this study, the potential
of exhaled breath (EB) as doping control specimen was assessed. METHODS: EB
collection devices employing a non-woven electret-based air filter unit were used
to generate test specimens, simulating a potential future application in doping
controls. A multi-analyte sports drug testing approach configured for a subset of
12 model compounds that represent specific classes of substances prohibited in
sports (anabolic agents, hormone and metabolic modulators, stimulants, and beta
blockers) was established using unispray liquid chromatography/tandem mass
spectrometry (LC/MS/MS) and applied to spiked and elimination study EB samples.
The test method was characterized concerning specificity, assay imprecision, and
limits of detection. RESULTS: The EB collection device allowed for retaining and
extracting all selected model compounds from the EB aerosol. Following elution
and concentration, LC/MS/MS analysis enabled detection limits between 5 and 100
pg/filter and imprecisions ranging from 3% to 20% for the 12 selected model
compounds. By means of EB samples from patients and participants of
administration studies, the elimination of relevant compounds and, thus, their
traceability in EB for doping control purposes, was investigated. Besides
stimulants such as methylhexaneamine and pseudoephedrine, also the anabolic
androgenic steroid dehydrochloromethyltestosterone, the metabolic modulator
meldonium, and the beta-blocker bisoprolol was detected in exhaled breath.
CONCLUSIONS: The EB aerosol has provided a promising proof-of-concept suggesting
the expansion of this testing strategy as a complement to currently utilized
sports drug testing programs.
PMID- 28508505
TI - Rapid switch-off of the human myosin heavy chain IIX gene after heavy load muscle
contractions is sustained for at least four days.
AB - Long-term heavy load contractions decrease the relative amount of the myosin
heavy chain (MHC) IIX isoform in human skeletal muscle, but the timing of the
down-regulation in the short term is unknown. Untrained subjects performed two
resistance bouts, in two consecutive days, with one leg, the other leg serving as
a control (age 24+/-1, n=5). Muscle biopsies were obtained in both legs before,
immediately after, and 24, 54, and 96 hours after exercise. Serial cryosection
analysis combined immunohistochemistry and ATPase histochemistry with In Situ
hybridization to identify the distribution of MHC isoforms and their
corresponding transcripts, enabling identification of transitional fibers. Fibers
positive solely for MHC IIX mRNA decreased in the exercised leg throughout the
study period. At 96 hours post-exercise, no fibers solely expressed MHC IIX mRNA.
In contrast, the number of fibers expressing MHC IIA mRNA increased throughout
the study period. The percentage of fibers expressing mRNA for MHC I was
unchanged in both legs at all time points. Pronounced depletion of glycogen in
the MHC IIX fibers of the exercised leg verifies that the type IIX fibers were
active during the heavy load contractions. Major mismatch between MHC at the mRNA
and protein levels was only found in the fibers of the exercised leg. These data
provide unequivocal in situ evidence of an immediate shutdown of the MHC IIX gene
after resistance exercise. A further novel finding was that the silencing of the
MHC IIX gene is sustained at least 4 days after removal of the stimulus.
PMID- 28508506
TI - Low-Voltage Photodetectors with High Responsivity Based on Solution-Processed
Micrometer-Scale All-Inorganic Perovskite Nanoplatelets.
AB - All-inorganic photodetectors based on scattered CsPbBr3 nanoplatelets with
lateral dimension as large as 10 um are fabricated, and the CsPbBr3 nanoplatelets
are solution processed governed by a newly developed ion-exchange soldering
mechanism. Under illumination of a 442 nm laser, the photoresponsivity of
photodetectors based on these scattered CsPbBr3 nanoplatelets is as high as 34 A
W-1 , which is the largest value reported from all-inorganic perovskite
photodetectors with an external driven voltage as small as 1.5 V. Moreover, the
rise and fall times are 0.6 and 0.9 ms, respectively, which are comparable to
most of the state-of-the-art all-inorganic perovskite-based photodetectors. All
the material synthesis and device characterization are conducted at room
temperature in ambient air. This work demonstrates that the solution-processed
large CsPbBr3 nanoplatelets are attractive candidates to be applied in low
voltage, low-cost, ultra highly integrated optoelectronic devices.
PMID- 28508507
TI - Detecting selection signatures between Duroc and Duroc synthetic pig populations
using high-density SNP chip.
AB - The development of high throughput genotyping techniques has facilitated the
identification of selection signatures of pigs. The detection of genomic
selection signals in a population subjected to differential selection pressures
may provide insights into the genes associated with economically and biologically
important traits. To identify genomic regions under selection, we genotyped 488
Duroc (D) pigs and 155 D * Korean native pigs (DKNPs) using the Porcine SNP70K
BeadChip. By applying the FST and extended haplotype homozygosity (EHH-Rsb)
methods, we detected genes under directional selection associated with
growth/stature (DOCK7, PLCB4, HS2ST1, FBP2 and TG), carcass and meat quality (TG,
COL14A1, FBXO5, NR3C1, SNX7, ARHGAP26 and DPYD), number of teats (LOC100153159
and LRRC1), pigmentation (MME) and ear morphology (SOX5), which are all mostly
near or at fixation. These results could be a basis for investigating the
underlying mutations associated with observed phenotypic variation. Validation
using genome-wide association analysis would also facilitate the inclusion of
some of these markers in genetic evaluation programs.
PMID- 28508508
TI - End Functionalized Nonionic Water-Dispersible Conjugated Polymers.
AB - 2,7-Dibromofluorene monomers carrying two or four oligo(ethylene glycol) (OEG)
side chains are synthesized. Heck coupling between the monomers and 1,4
divinylbenzene followed by end capping with [4-(4-bromophenoxy)butyl]carbamic
acid tert-butyl ester leads to two nonionic water-dispersible poly(fluorene-alt
1,4-divinylenephenylene)s end-functionalized with amine groups after hydrolysis.
In water, the polymer with a lower OEG density (P1) has poor water dispersibility
with a quantum yield of 0.24, while the polymer with a higher OEG density (P2)
possesses excellent water-dispersibility with a high quantum yield of 0.45. Both
polymers show fluorescence enhancement and blue-shifted absorption and emission
maxima in the presence of surfactant sodium dodecyl sulfate and
dodecyltrimethylammonium bromide. The polymers are also resistant to ionic
strength with minimal nonspecific interactions to bovine serum albumin. When
biotin is incorporated into the end of the polymer backbones through N
hydroxysuccinimide/amine coupling reaction, the biotinylated polymers interact
specifically with streptavidin on solid surface.
PMID- 28508509
TI - Investigating the inter-subunit/subdomain interactions and motions relevant to
disease mutations in the N-terminal domain of ryanodine receptors by molecular
dynamics simulation.
AB - The ryanodine receptors (RyR) are essential to calcium signaling in striated
muscles, and numerous disease mutations have been identified in two RyR isoforms,
RyR1 in skeletal muscle and RyR2 in cardiac muscle. A deep understanding of the
activation/regulation mechanisms of RyRs has been hampered by the shortage of
high-resolution structures and dynamic information for this giant tetrameric
complex in different functional states. Toward elucidating the molecular
mechanisms of disease mutations in RyRs, we performed molecular dynamics
simulation of the N-terminal domain (NTD) which is not only the best-resolved
structural component of RyRs, but also a hotspot of disease mutations. First, we
simulated the tetrameric NTD of wild-type RyR1 and three disease mutants (K155E,
R157Q, and R164Q) that perturb the inter-subunit interfaces. Our simulations
identified a dynamic network of salt bridges involving charged residues at the
inter-subunit/subdomain interfaces and disease-mutation sites. By perturbing this
key network, the above three mutations result in greater flexibility with the
highest inter-subunit opening probability for R157Q. Next, we simulated the
monomeric NTD of RyR2 in the presence or absence of a central Cl- anion which is
known to stabilize the interfaces between the three NTD subdomains (A, B, and C).
We found that the loss of Cl- restructures the salt-bridge network near the Cl-
binding site, leading to rotations of subdomain A/B relative to subdomain C and
enhanced mobility between the subdomains. This finding supports a mechanism for
disease mutations in the NTD of RyR2 via perturbation of the Cl- binding. The
rich structural and dynamic information gained from this study will guide future
mutational and functional studies of the NTD of RyRs. Proteins 2017; 85:1633
1644. (c) 2017 Wiley Periodicals, Inc.
PMID- 28508510
TI - Impaired atrioventricular transport in patients with transposition of the great
arteries palliated by atrial switch and preserved systolic right ventricular
function: A magnetic resonance imaging study.
AB - OBJECTIVES: We aimed (1) determine if systemic right ventricle filling parameters
influence systemic right ventricle stroke volume in adult patients with D
transposition of the great arteries (D-TGA) palliated by atrial switch, using
cardiac magnetic resonance imaging and echocardiography, and (2) to study
relationship of these diastolic parameters with exercise performance and BNP, in
patients with preserved systolic systemic right ventricle function. DESIGN:
Single-center, cross-sectional, prospective study. SETTING: In patients with D
TGA palliated by atrial switch, diastolic dysfunction of the systemic right
ventricle may precede systolic dysfunction. METHODS: Forty-five patients with D
TGA and atrial switch and 45 age and sex-matched healthy subjects underwent
cardiac magnetic resonance imaging and echocardiography. Filling flow-rates
measured by phase-contrast cardiac magnetic resonance imaging were analyzed using
customized software to estimate diastolic parameters and compared with exercise
performance. RESULTS: In D-TGA, early filling of systemic right ventricle was
impaired with a lower peak filling rate normalized by filling volume (Ef/FV
measured by cardiac magnetic resonance imaging) and a higher early filling peak
velocity normalized by early peak myocardial velocity (EUS /Ea measured by
echocardiography) compared with controls (P <= .04). Stroke volume of systemic
right ventricle showed a direct and significant association with pulmonary venous
pathway size (respectively r = 0.50, P < .01). Systemic right atrial area and
systemic right ventricle mass/volume index measured by cardiac magnetic resonance
imaging, as well as Ef/FV were significantly correlated with exercise
performances and BNP (P < .01). All correlations were independent of age, gender,
body mass index and blood pressure. CONCLUSIONS: Systemic right ventricle pre
load and stroke volume depend mainly on intraatrial pathway function. Moreover,
systemic right ventricle remodeling and right atrial dysfunction impair systemic
right ventricle filling, leading to BNP increase and exercise limitation. Cardiac
magnetic resonance imaging should assess systemic right ventricle filling
abnormalities in D-TGA patients.
PMID- 28508511
TI - Clinical, nociceptive and psychological profiling to predict acute pain after
total knee arthroplasty.
AB - BACKGROUND: Pre-operative identification of high-pain responders for acute pain
after total knee arthroplasty (TKA) could lead to targeted analgesic trials and
individualized analgesic strategies to improve recovery and potentially reduce
the risk of persistent post-surgical pain. The aim of this study was to use
simple clinical tests and questionnaires to identify predictive nociceptive and
psychological factors for acute post-TKA pain. METHODS: Sixty consecutive TKA
patients were included in a prospective descriptive study of pain during a 5-m
walk-test 24 h post-operatively as the primary outcome. Predictive variables
collected prior to surgery included demographics, nociceptive testing (pressure
pain threshold (PPT), cold pressor tolerance, electrical pain threshold and
tolerance) and psychological profile (pain catastrophizing scale (PCS) and
hospital anxiety and depression scale). The prediction of acute post-TKA pain was
assessed by univariate analysis, logistic regressions and ROC curves. RESULTS:
Reduced PPT on the arm and increased PCS were predictive variables for
moderate/severe post-TKA pain 24 h after surgery (P = 0.007 and P = 0.026,
respectively, R-squared 0.21) in the logistic regression model. Odds ratios were
0.67 for a 50 kPa increased PPT and 1.36 for a 5 point increase in PCS. A
predictive model with cut-off values of PPT <= 245 kPa and PCS>= 8 point had a
sensitivity of 71.4 and a specificity of 62.5. CONCLUSION: Pre-operative
widespread pressure pain hypersensitivity and pain catastrophizing are predictive
of moderate severe post-TKA pain. If validated in a larger population, the
clinically applicable tests should be considered in future interventions aiming
to minimize post-operative pain in high-risk patients.
PMID- 28508512
TI - Ultralight Multifunctional Carbon-Based Aerogels by Combining Graphene Oxide and
Bacterial Cellulose.
AB - Nanostructured carbon aerogels with outstanding physicochemical properties have
exhibited great application potentials in widespread fields and therefore
attracted extensive attentions recently. It is still a challenge so far to
develop flexible and economical routes to fabricate high-performance nanocarbon
aerogels, preferably based on renewable resources. Here, ultralight and
multifunctional reduced graphene oxide/carbon nanofiber (RGO/CNF) aerogels are
fabricated from graphene oxide and low-cost, industrially produced bacterial
cellulose by a three-step process of freeze-casting, freeze-drying, and
pyrolysis. The prepared RGO/CNF aerogel possesses a very low apparent density in
the range of 0.7-10.2 mg cm-3 and a high porosity up to 99%, as well as a
mechanically robust and electrically conductive 3D network structure, which makes
it to be an excellent candidate as absorber for oil clean-up and an ideal
platform for constructing flexible and stretchable conductors.
PMID- 28508513
TI - Synthesis and Trapping of Iminoboranes by M=B/C=N Bond Metathesis.
AB - Although the metathesis of metal-boron double bonds with elemental chalcogenides
is an established process, no similar reactivity has been observed with element
nitrogen bonds. Such a reaction would provide a new route to iminoborane
compounds (RB=NR'), which have recently experienced renewed synthetic interest.
Herein, we present the first observation of M=B/C=N metathesis reactions, which
led to the isolation of a stable iminoborane in addition to further iminoborane
cycloaddition products.
PMID- 28508514
TI - Migraine prevalence in inflammatory bowel disease patients: A tertiary-care
centre cross-sectional study.
AB - BACKGROUND: Inflammatory bowel diseases (IBD) are systemic, chronic inflammatory
conditions that predominately affect the gastrointestinal tract and can induce
abdominal pain. Besides, many IBD patients complain about headaches in daily
practice. The objective was to assess the prevalence of headaches, including
migraines and pain with neuropathic characteristics (NC), in IBD patients
compared to historical controls from the general population. METHODS: Overall,
203 consecutive tertiary-care centre patients completed validated self
administered questionnaires and benefitted from a clinical evaluation performed
by an IBD physician at the same time. RESULTS: In our cohort, 75% of the patients
experienced pain in the previous 3 months. Migraine prevalence was two-fold
higher in IBD patients compared to the general population (41% vs. 21.3%, p <
0.001). Migraine was associated with a younger age, female gender and higher
depression scores. Although migraine impact was very important for 30% of the
patients (61/203), specific acute therapeutics were prescribed in only 22% of
cases (18/83). Chronic pain with NC was more frequent than in the general
population (11.3% vs. 6.9%, p = 0.012) and was strongly associated with the
presence of extra-intestinal manifestations (p < 0.001). Abdominal pain concerned
19% of the patients during the previous week and was, as expected, associated
with disease activity. CONCLUSIONS: Migraine prevalence is strongly increased in
IBD patients followed in tertiary care. A systematic screening for migraine
should be done by IBD physicians in daily practice to provide adequate
therapeutics. Further studies are needed to confirm whether migraine should be
classified as IBD extra-intestinal manifestations. SIGNIFICANCE: Migraine
prevalence was two-fold higher in IBD patients compared to the general
population, was generally poorly treated and a systematic screening for migraine
should be done by IBD physicians in daily practice to provide adequate
therapeutics.
PMID- 28508515
TI - Extra oral digital scanning and imaging superimposition for volume analysis of
bone remodeling after tooth extraction with and without 2 types of particulate
porcine mineral insertion: A randomized controlled trial.
AB - BACKGROUND: Incorporation of bone substitute material into the extraction socket
could minimize the edentulous ridge volume loss or maximize the bone formation
within the healing area. PURPOSE: The aim of the study was to test the
effectiveness in maintaining the volumetric contour of fresh extraction sockets
grafted with or without 2 types of porcine biomaterials and covered with a
resorbable barrier. MATERIALS AND METHODS: In the present multi-center single
blind randomized control trial, 55 patients underwent 1-tooth extraction, were
surveyed, and randomly allocated to control- (25 sites, nat-group) or test groups
(15 sites grafted with pre-hydrated collagenated cortico-cancellous porcine bone,
coll-group, and 15 with cortical porcine bone, cort-group). Before extraction,
and then 4 months later, contours of the sockets were acquired through a laser
scanner, voxelized, and ghosts of each patient were superimposed with a matrix
laboratory. Volumetric and area evaluations of the virtual superimposed models
were performed with dentascan tools to create a volume of interest extending
between the 2 residual teeth. Intra- and inter-group comparisons of the outcomes
were performed. Non-parametric tests were applied with a level of significance
set at P < .05. RESULTS: Intergroup analysis at 4 months' survey revealed that
percentage loss of alveolar ridge volume of the coll-group (28.8% +/- 8.8%) and
of the cort-group (30.2% +/- 7.1%) was significantly lower (P < .0001) than that
of the naturally-healing group (46.4% +/- 4.1%). No statistically-significant
differences in outcomes were observed between the 2 test groups at any of the
observation periods. Moreover, tooth position (bicuspids vs molars) seemed to
affect neither volume loss nor basal shrinkage. CONCLUSION: At the 4-month
analysis both test groups showed reduced bone loss when compared to naturally
healing sockets. However, the 2 grafting materials were not able to preserve the
alveolar crest, and a reduction close to 30% in the estimates was registered
after healing.
PMID- 28508517
TI - On-demand Antimicrobial Treatment with Antibiotic-Loaded Porous Silicon Capped
with a pH-Responsive Dual Plasma Polymer Barrier.
AB - Chronic wounds are a major socio-economic problem. Bacterial infections in such
wounds are a major contributor to lack of wound healing. An early indicator of
wound infection is an increase in pH of the wound fluid. Herein, we describe the
development of a pH-responsive drug delivery device that can potentially be used
for wound decontamination in situ and on-demand in response to an increase in the
pH of the wound environment. The device is based on a porous silicon film that
provides a reservoir for encapsulation of an antibiotic within the pores. Loaded
porous silicon is capped with dual plasma polymer layers of poly(1,7-octadiene)
and poly(acrylic acid), which provide a pH-responsive barrier for on-demand
release of the antibiotic. We demonstrate that release of the antibiotic is
inhibited in aqueous buffer at pH 5, whereas the drug is released in a
sustainable manner at pH 8. Importantly, the released drug was bacteriostatic
against the Pseudomonas aeruginosa wound pathogen. In the future, incorporation
of the delivery device into wound dressings could potentially be utilized for non
invasive decontamination of wounds.
PMID- 28508518
TI - Alcohol marketing and youth drinking in Asia.
PMID- 28508519
TI - Fetal cardiac remodeling in twin pregnancy conceived by assisted reproductive
technology.
AB - OBJECTIVE: Recent data suggest that singleton fetuses conceived by assisted
reproductive technology (ART) present cardiovascular remodeling that may persist
postnatally. Twin pregnancies are more frequent in the ART population and are
associated with increased adverse perinatal outcomes, such as hypertensive
disorders, gestational diabetes and preterm birth. However, it is unknown whether
cardiac remodeling is also present in twin pregnancies conceived by ART. Our aim
was to assess the presence of fetal cardiac remodeling and dysfunction in twin
pregnancies conceived by ART as compared with those conceived spontaneously (SC).
METHODS: This was a prospective cohort study including 50 dichorionic twin
fetuses conceived by ART and 50 SC twin fetuses. The study protocol included
collection of baseline/perinatal data and a fetal ultrasound examination at 28-30
weeks' gestation, including assessment of estimated fetal weight, fetoplacental
Doppler and fetal echocardiography. Measurements of atrial area, atrial/heart
ratio, ventricular sphericity index, free wall thickness, mitral and tricuspid
annular plane systolic excursions, and systolic and early diastolic peak
velocities were assessed. Multilevel analyses were used to compare perinatal and
ultrasonographic parameters. Comparisons of echocardiographic variables were
adjusted for parental age, paternal body mass index and incidence of pre
eclampsia. RESULTS: Compared with SC twins, ART twin fetuses showed significant
cardiac changes, predominantly affecting the right heart, such as dilated atria
(right atrial/heart area: 15.7 +/- 3.1 vs 18.4 +/- 3.2, P < 0.001), more globular
ventricles (right ventricular sphericity index: 1.57 +/- 0.25 vs 1.41 +/- 0.23, P
= 0.001) and thicker myocardial walls (septal wall thickness: 2.57 +/- 0.45 mm vs
2.84 +/- 0.41 mm, P = 0.034) together with reduced longitudinal motion (tricuspid
annular plane systolic excursion: 6.36 +/- 0.89 mm vs 5.18 +/- 0.93 mm, P <
0.001). CONCLUSIONS: ART twin fetuses present signs of cardiac remodeling and
dysfunction. These changes are similar to those observed in ART singletons and
reinforce the concept of fetal cardiac programing in ART. These results open
opportunities for early detection and intervention in infants conceived by ART.
Copyright (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.
PMID- 28508516
TI - Fell Muir Lecture: Collagen fibril formation in vitro and in vivo.
AB - It is a great honour to be awarded the Fell Muir Prize for 2016 by the British
Society of Matrix Biology. As recipient of the prize, I am taking the opportunity
to write a minireview on collagen fibrillogenesis, which has been the focus of my
research for 33 years. This is the process by which triple helical collagen
molecules assemble into centimetre-long fibrils in the extracellular matrix of
animals. The fibrils appeared a billion years ago at the dawn of multicellular
animal life as the primary scaffold for tissue morphogenesis. The fibrils occur
in exquisite three-dimensional architectures that match the physical demands of
tissues, for example orthogonal lattices in cornea, basket weaves in skin and
blood vessels, and parallel bundles in tendon, ligament and nerves. The question
of how collagen fibrils are formed was posed at the end of the nineteenth
century. Since then, we have learned about the structure of DNA and the peptide
bond, understood how plants capture the sun's energy, cloned animals, discovered
antibiotics and found ways of editing our genome in the pursuit of new cures for
diseases. However, how cells generate tissues from collagen fibrils remains one
of the big unsolved mysteries in biology. In this review, I will give a personal
account of the topic and highlight some of the approaches that my research group
are taking to find new insights.
PMID- 28508520
TI - Palladium(I) Dimer Enabled Extremely Rapid and Chemoselective Alkylation of Aryl
Bromides over Triflates and Chlorides in Air.
AB - Disclosed herein is the first general chemo- and site-selective alkylation of C
Br bonds in the presence of COTf, C-Cl and other potentially reactive functional
groups, using the air-, moisture-, and thermally stable dinuclear PdI catalyst,
[Pd(MU-I)PtBu3 ]2 . The bromo-selectivity is independent of the substrate and the
relative positioning of the competing reaction sites, and as such fully
predictable. Primary and secondary alkyl chains were introduced with extremely
high speed (<5 min reaction time) at room temperature and under open-flask
reaction conditions.
PMID- 28508521
TI - An Incidental Diffuse Midline Glioma Found at Autopsy.
AB - This case shows an unexpected midline glioma found at autopsy. Two siblings were
riding on a single bicycle on the side of a road. The 13-year-old brother was
seated and steering the bicycle, while the 14-year-old sister held onto the back.
The bicycle veered left into traffic and was struck by a vehicle. The siblings
were admitted to the local Level 1 trauma center, but both later succumbed to
injuries. Autopsies were performed on the children, including brains for
neuropathologic evaluation. The brother was found to have an infiltrating
astrocytoma located in the left middle cerebellar peduncle, with extension to the
pons and medulla. His hospital course included several imaging studies using CT
and MRI modalities. However, this lesion was not identified until the postmortem
neuropathologic examination. This rare case shows the continued need for
postmortem autopsy and the current limitations of medical imaging.
PMID- 28508522
TI - In Situ Observation of Twin Boundary Sliding in Single Crystalline Cu Nanowires.
AB - Using a homemade, novel, in situ transmission electron microscopy (TEM) double
tilt tensile device, plastic behavior of single crystalline Cu nanowires of
around 150 nm are studied. Deformation twins occur during the tests as
predesigned before the experiments. In situ observation of twin boundary sliding
(TBS) caused by full dislocation (extended dislocation) is first revealed at the
atomic scale which is confirmed by molecular dynamics (MD) simulation results.
Combined with twin boundary migration and multiple dislocations nucleated from
surface, TBS causes a superlarge fracture strain which is over 166% and a severe
necking which is over 93%, far beyond the typical values for most nanomaterials
without twins.
PMID- 28508523
TI - The effect of sodium hypochlorite concentration and irrigation needle extension
on biofilm removal from a simulated root canal model.
AB - To investigate the effect of sodium hypochlorite concentration and needle
extension on removal of Enterococcus faecalis biofilm, sixty root canal models
were 3D printed. Biofilms were grown on the apical 3 mm of the canal for 10 days.
Irrigation for 60s with 9 mL of either 5.25% or 2.5% NaOCl or water was performed
using a needle inserted either 3 or 2 mm from the canal terminus and imaged using
fluorescence microscopy and residual biofilm percentages were calculated using
imaging software. The data were analysed using analysis of covariance and two
sample t-tests. A significance level of 0.05 was used throughout. Residual
biofilm was less using 5.25% than with 2.5% NaOCl. Statistically significant
biofilm removal was evident with the needle placed closer to the canal terminus.
A greater reduction of available chlorine and pH was noted as the concentration
increased. One-minute irrigation was not sufficient for complete biofilm removal.
PMID- 28508524
TI - A Carbon Dioxide Bubble-Induced Vortex Triggers Co-Assembly of Nanotubes with
Controlled Chirality.
AB - It is challenging to prepare co-organized nanotube systems with controlled
nanoscale chirality in an aqueous liquid flow field. Such systems are responsive
to a bubbled external gas. A liquid vortex induced by bubbling carbon dioxide
(CO2 ) gas was used to stimulate the formation of nanotubes with controlled
chirality; two kinds of achiral cationic building blocks were co-assembled in
aqueous solution. CO2 -triggered nanotube formation occurs by formation of
metastable intermediate structures (short helical ribbons and short tubules) and
by transition from short tubules to long tubules in response to chirality
matching self-assembly. Interestingly, the chirality sign of these assemblies can
be selected for by the circulation direction of the CO2 bubble-induced vortex
during the co-assembly process.
PMID- 28508526
TI - A complex case of ibrutinib treatment for a CLL patient on haemodialysis.
PMID- 28508525
TI - The Structural Fate of Individual Multicomponent Metal-Oxide Nanoparticles in
Polymer Nanoreactors.
AB - Multicomponent nanoparticles can be synthesized with either homogeneous or phase
segregated architectures depending on the synthesis conditions and elements
incorporated. To understand the parameters that determine their structural fate,
multicomponent metal-oxide nanoparticles consisting of combinations of Co, Ni,
and Cu were synthesized by using scanning probe block copolymer lithography and
characterized using correlated electron microscopy. These studies revealed that
the miscibility, ratio of the metallic components, and the synthesis temperature
determine the crystal structure and architecture of the nanoparticles. A Co-Ni-O
system forms a rock salt structure largely owing to the miscibility of CoO and
NiO, while Cu-Ni-O, which has large miscibility gaps, forms either homogeneous
oxides, heterojunctions, or alloys depending on the annealing temperature and
composition. Moreover, a higher-ordered structure, Co-Ni-Cu-O, was found to
follow the behavior of lower ordered systems.
PMID- 28508527
TI - Complete remission of primary cutaneous intravascular large B-cell lymphoma with
R-CHOP followed by rituximab monotherapy.
PMID- 28508528
TI - Competing-risks model in screening for pre-eclampsia in twin pregnancy by
maternal characteristics and medical history.
AB - OBJECTIVE: A survival-time regression model for gestational age at delivery with
pre-eclampsia (PE) in singleton pregnancy, using maternal demographic
characteristics and medical history, was reported previously. The objective of
this study was to extend this model to dichorionic (DC) and monochorionic (MC)
twin pregnancy. METHODS: The study population included 1789 DC and 430 MC twin
pregnancies and 93 297 singleton pregnancies. A survival-time model for
gestational age at delivery with PE was developed from variables of maternal
characteristics and medical history. The risk of PE with delivery < 37 weeks and
< 42 weeks in twin pregnancies was determined and compared with that in singleton
pregnancies. RESULTS: In singleton pregnancies comprising women of Caucasian
racial origin, mean weight of 69 kg at 12 weeks' gestation, mean height of 164
cm, nulliparous, with spontaneous conception, no family history of PE and no
history of diabetes mellitus, systemic lupus erythematosus or antiphospholipid
syndrome, the mean of the Gaussian distribution of gestational age at delivery
with PE was 55 weeks. In DC twins with PE, mean gestational age at delivery was
shifted to the left by 8.2 (95% CI, 7.2-9.1) weeks and in MC twins it was shifted
to the left by 10.0 (95% CI, 8.5-11.4) weeks. The risk of delivery with PE
occurring at, or before, a specified gestational age is given by the area under
the fitted distribution curve. For a reference population with the above
characteristics, the estimated risk of PE < 37 weeks' gestation, assuming no
other cause of delivery, was 0.6% for singletons, 9.0% for DC twins and 14.2% for
MC twins; the respective values for PE < 42 weeks were 3.6%, 27.0% and 36.5%.
CONCLUSIONS: A model based on maternal characteristics and medical history has
been developed for estimation of patient-specific risks for PE in DC and MC twin
pregnancy. Such estimation of the a-priori risk for PE is an essential first step
in the use of Bayes' theorem to combine maternal factors with biomarkers for the
continuing development of more effective methods of screening for the disease.
Copyright (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.
PMID- 28508529
TI - Mastery Learning - does the method of learning make a difference in skills
acquisition for robotic surgery?
AB - BACKGROUND: Few studies compare the effectiveness of blocked vs random practice
conditions in minimally invasive surgery training, and none have evaluated these
in robotic surgery training. METHODS: The dV-Trainer(r) and the da Vinci(r)
Surgical System (dVSS) were used to compare practice conditions. Forty-two
participants were randomized into blocked and random practice groups. Each
participant performed five tasks: Ring Walk, Thread the Rings, Needle Targeting,
Suture Sponge and Tubes Level 2. Transfer to the dVSS was also assessed. RESULTS:
No significant differences were observed between the two groups, except for a few
instances. For example, during Ring Walk, the random group performed
significantly faster than the blocked group (100.78 +/- 5.26 s vs 121.59 +/- 5.26
s, p < 0.01). CONCLUSIONS: The study results do not follow the current evidence
presented in the education literature. This is the first time that blocked versus
random practice was tested for robotic surgery training.
PMID- 28508530
TI - Seventeen-Coordinate Actinide Helium Complexes.
AB - The geometries and electronic structures of molecular ions featuring He atoms
complexed to actinide cations are explored computationally using density
functional and coupled cluster theories. A new record coordination number is
established, as AcHe173+ , ThHe174+ , and PaHe174+ are all found to be true
geometric minima, with the He atoms clearly located in the first shell around the
actinide. Analysis of AcHen3+ (n=1-17) using the quantum theory of atoms in
molecules (QTAIM) confirms these systems as having closed shell, charge-induced
dipole bonding. Excellent correlations (R2 >0.95) are found between QTAIM metrics
(bond critical point electron densities and delocalization indices) and the
average Ac-He distances, and also with the incremental He binding energies.
PMID- 28508531
TI - Avoiding experimental death: the EQUATOR network (a valuable resource for
research).
PMID- 28508532
TI - Aortic valve replacement for papillary fibroelastoma.
AB - Surgery is indicated for symptomatic patients with papillary fibroelastomas (PFE)
on the aortic valve. The valve is commonly spared during tumor excision. Rarely,
aortic valve replacement (AVR) is needed. We present a case requiring AVR for an
aortic valve PFE and review the literature to determine the risk factors for
failure of aortic valve-sparing techniques in patients with PFE.
PMID- 28508533
TI - Intermolecular Charge-Transfer Interactions Facilitate Two-Photon Absorption in
Styrylpyridine-Tetracyanobenzene Cocrystals.
AB - Cocrystals of 4-styrylpyridine and 1,2,4,5-tetracyanobenzene were successfully
prepared by supramolecular self-assembly. Donor-acceptor interactions between the
molecular components are the main driving force for self-assembly and contribute
to intermolecular charge transfer. The cocrystals possess two-photon absorption
properties that are not observed in the individual components; suggesting that
two-photon absorption originates from intermolecular charge-transfer interactions
in the donor-acceptor system. The origin of two-photon absorption in
multichromophore systems remains under-researched; thus, the system offers a rare
demonstration of two-photon absorption by cocrystallization. Cocrystal
engineering may facilitate further design and development of novel materials for
nonlinear optical and optoelectronic applications.
PMID- 28508534
TI - Large-Scale Suspended Graphene Used as a Transparent Substrate for Infrared
Spectroscopy.
AB - Due to weak interactions between micrometer-wavelength infrared (IR) light and
nanosized samples, a high signal to noise ratio is a prerequisite in order to
precisely characterize nanosized samples using IR spectroscopy. Traditional
micrometer-thick window substrates, however, have considerable IR absorption
which may introduce unavoidable deformations and interruptions to IR spectra of
nanoscale samples. A promising alternative is the use of a suspended graphene
substrate which has ultrahigh IR transmittance (>97.5%) as well as unique
mechanical properties. Here, an effective method is presented for fabrication of
suspended graphene over circular holes up to 150 um in diameter to be utilized as
a transparent substrate for IR spectroscopy. It is demonstrated that the
suspended graphene has little impact on the measured IR spectra, an advantage
which has led to the discovery of several missing vibrational modes of a 20 nm
thick PEO film measured on a traditional CaF2 substrate. This can provide a
better understanding of molecules' fine structures and status of hanging bands.
The unique optical properties of suspended graphene are determined to be superior
to those of conventional IR window materials, giving this new substrate great
potential as part of a new generation of IR transparent substrates, especially
for use in examining nanoscale samples.
PMID- 28508535
TI - Costimulation Blockade: America First, Canada Second ... What About Norway?
PMID- 28508536
TI - Risankizumab versus ustekinumab for moderate-to-severe plaque psoriasis.
PMID- 28508537
TI - Superorganismality and caste differentiation as points of no return: how the
major evolutionary transitions were lost in translation.
AB - More than a century ago, William Morton Wheeler proposed that social insect
colonies can be regarded as superorganisms when they have morphologically
differentiated reproductive and nursing castes that are analogous to the metazoan
germ-line and soma. Following the rise of sociobiology in the 1970s, Wheeler's
insights were largely neglected, and we were left with multiple new superorganism
concepts that are mutually inconsistent and uninformative on how
superorganismality originated. These difficulties can be traced to the broadened
sociobiological concept of eusociality, which denies that physical queen-worker
caste differentiation is a universal hallmark of superorganismal colonies. Unlike
early evolutionary naturalists and geneticists such as Weismann, Huxley, Fisher
and Haldane, who set out to explain the acquisition of an unmated worker caste,
the goal of sociobiology was to understand the evolution of eusociality, a broad
brush convenience category that covers most forms of cooperative breeding. By
lumping a diverse spectrum of social systems into a single category, and drawing
attention away from the evolution of distinct quantifiable traits, the
sociobiological tradition has impeded straightforward connections between
inclusive fitness theory and the major evolutionary transitions paradigm for
understanding irreversible shifts to higher organizational complexity. We
evaluate the history by which these inconsistencies accumulated, develop a common
cause approach for understanding the origins of all major transitions in
eukaryote hierarchical complexity, and use Hamilton's rule to argue that they are
directly comparable. We show that only Wheeler's original definition of
superorganismality can be unambiguously linked to irreversible evolutionary
transitions from context-dependent reproductive altruism to unconditional
differentiation of permanently unmated castes in the ants, corbiculate bees,
vespine wasps and higher termites. We argue that strictly monogamous parents were
a necessary, albeit not sufficient condition for all transitions to
superorganismality, analogous to single-zygote bottlenecking being a necessary
but not sufficient condition for the convergent origins of complex soma across
multicellular eukaryotes. We infer that conflict reduction was not a necessary
condition for the origin of any of these major transitions, and conclude that
controversies over the status of inclusive fitness theory primarily emanate from
the arbitrarily defined sociobiological concepts of superorganismality and
eusociality, not from the theory itself.
PMID- 28508539
TI - The effect of maternal obesity on fatty acid transporter expression and lipid
metabolism in the full-term placenta of lean breed swine.
AB - This study was conducted to evaluate the influence of back-fat thickness (BF), at
mating of sows, on the maternal and newborn circulating lipids, expression of
placental fatty acids (FA) transporters and lipid accumulation in placenta. Full
term placentas were obtained by vaginal delivery from BFI (9-14 mm; n = 37), BFII
(15-19 mm; n = 43) and BFIII (20-27 mm; n = 38) sows according to BF at mating,
and frozen placental sections were analysed for fat accumulation. Blood samples
were collected from the sows of day 105 pregnancy and from cord blood at
delivery. mRNA and protein expression levels were evaluated with real-time RT-PCR
and Western blotting. Our results demonstrated that BFII females had
significantly increased litter weight and placental efficiency, decreased
maternal triglyceride (TG) and non-esterified fatty acids (NEFA) levels,
decreased maternal IL-6, TNFalpha and leptin levels compared to BFIII females (p
< .05). BFIII sows were associated with significantly decreased newborn TG
levels, increased newborn glucose, IL-6 and TNFalpha levels compared to BFI or
BFII sows (p < .05). BFI and BFII females had significantly decreased placental
TG, NEFA and cholesterol (CHOL) contents compared to BFIII females (p < .05).
Moreover, decreased CD36, FATP1, FABP4, and FABP1 mRNA and protein and FATP4
protein expression, and increased LPL activity were also observed in BFIII group
compared with BFII group (p < .05). PPARgamma mRNA and protein and lipogenic
genes such as SREBP-1c, ACSL1, ACCalpha, FAS and SCD mRNA expression were
downregulated or upregulated, respectively, in the placentas of BFIII sows
compared to BFI or BFII sows (p < .05). Overall, this study demonstrated that
there is no advantage, in terms of litter live size, litter weight and placental
FA transport and metabolism, in performing the mating of sows with BF>19 mm.
PMID- 28508538
TI - Prognostic Value of Predialysis Indices for Technique Failure and Mortality in
Peritoneal Dialysis Patients.
AB - Technique failure remains a frequent cause of peritoneal dialysis (PD)
withdrawal. Many post-commencement predictors of PD technique failure have been
identified, while predialysis predictors have remained unclear. The aim of this
study was to identify predialysis indices for technique failure in PD patients.
We recruited 206 consecutive PD patients who were treated at Nara Medical
University Hospital between 1 April 1997 and 31 December 2012. Forty-eight
patients were excluded because of transition from hemodialysis (HD) or withdrawal
from PD within 3 months, leaving 158 patients for analysis. Clinical
characteristics and laboratory data from within 3 months preceding PD
commencement were analyzed. The primary outcome was the composite of time to
combined use of HD, transition to HD, and all-cause mortality within 2 years
after PD commencement. During the study period, the primary outcome was observed
in 50 patients. Using multivariate analysis, greater age (odds ratios (ORs)
[95%CI], 3.08 [1.72-5.61]), anemia (ORs [95%CI], 2.12 [1.08-4.43]),
overweight/obesity (ORs [95%CI], 2.09 [1.16-3.72]), and hypocalcemia (ORs
[95%CI], 1.86 [1.04-3.35]) were independently associated with technique failure.
Adding corrected calcium to the model incorporating age, body mass index, and
hemoglobin significantly increased the c-statistic from 0.678 to 0.755 (P =
0.048) relative to the model incorporating age alone. The integrated
discrimination improvement was 0.085 (95% CI 0.036-0.134, P < 0.001) and the
continuous net reclassification improvement was 0.395 (95% CI 0.066-0.724, P =
0.02). In conclusion, the combination of predialysis indices comprising age,
overweight/obesity, anemia, and corrected calcium could provide a significant
predictive value for technique failure of PD.
PMID- 28508540
TI - Recurrent fetal thyrotoxicosis in woman with history of Hashimoto's thyroiditis.
PMID- 28508541
TI - Opt-in or opt-out to increase organ donation in South Africa? Appraising proposed
strategies using an empirical ethics analysis.
AB - Utilising empirical ethics analysis, we evaluate the merits of systems proposed
to increase deceased organ donation in South Africa (SA). We conclude that SA
should maintain its soft opt-in policy, and enhance it with 'required transplant
referral' in order to maximise donor numbers within an ethically and legally
acceptable framework. In SA, as is the case worldwide, the demand for donor
organs far exceeds the supply thereof. Currently utilising a soft opt-in system,
SA faces the challenge of how to increase donor numbers in a context which is
imbued with inequalities in access to healthcare, multiplicitous personal beliefs
and practices, distrust of organ transplant and varying levels of education and
health literacy. We argue that a hard opt-in, opt-out or mandated consent system
would be problematic, and we present empirical data from Gauteng Province
illustrating barriers to ethically sound practice in soft consent systems.
Ultimately, we argue that in spite of some limitations, a soft opt-in system is
most realistic for SA because its implementation does not require extensive
public education campaigns at national level, and it does not threaten to further
erode trust at a clinical level. However, to circumvent some of the clinical
level barriers identified in our empirical study, we propose a contextually
sensitive option for "enabling" soft opt-in through "required transplant
referral". We argue that this system is legally defensible, enhances ethical
practice and could also increase donor numbers as it has in many other countries.
PMID- 28508542
TI - Dynamic Self-Assembly of Homogenous Microcyclic Structures Controlled by a Silver
Coated Nanopore.
AB - The self-assembly of nanoparticles is a challenging process for organizing
precise structures with complicated and ingenious structures. In the past
decades, a simple, high-efficiency, and reproducible self-assembly method from
nanoscale to microscale has been pursued because of the promising and extensive
application prospects in bioanalysis, catalysis, photonics, and energy storage.
However, microscale self-assembly still faces big challenges including improving
the stability and homogeneity as well as pursuing new assembly methods and
templates for the uniform self-assembly. To address these obstacles, here, a
novel silver-coated nanopore is developed which serves as a template for
electrochemically generating microcyclic structures of gold nanoparticles at
micrometers with highly homogenous size and remarkable reproducibility. Nanopore
induced microcyclic structures are further applied to visualize the diffusion
profile of ionic flux. Based on this novel strategy, a nanopore could potentially
facilitate the delivery of assembled structures for many practical applications
including drug delivery, cellular detection, catalysis, and plasmonic sensing.
PMID- 28508543
TI - True Transsphenoidal Meningoencephalocele.
PMID- 28508544
TI - A Decision Tree for Nonmetric Sex Assessment from the Skull.
AB - This study uses five well-documented cranial nonmetric traits (glabella, mastoid
process, mental eminence, supraorbital margin, and nuchal crest) and one
additional trait (zygomatic extension) to develop a validated decision tree for
sex assessment. The decision tree was built and cross-validated on a sample of
293 U.S. White individuals from the William M. Bass Donated Skeletal Collection.
Ordinal scores from the six traits were analyzed using the partition modeling
option in JMP Pro 12. A holdout sample of 50 skulls was used to test the model.
The most accurate decision tree includes three variables: glabella, zygomatic
extension, and mastoid process. This decision tree yielded 93.5% accuracy on the
training sample, 94% on the cross-validated sample, and 96% on a holdout
validation sample. Linear weighted kappa statistics indicate acceptable agreement
among observers for these variables. Mental eminence should be avoided, and
definitions and figures should be referenced carefully to score nonmetric traits.
PMID- 28508545
TI - Comparison of joint modeling and landmarking for dynamic prediction under an
illness-death model.
AB - Dynamic prediction incorporates time-dependent marker information accrued during
follow-up to improve personalized survival prediction probabilities. At any
follow-up, or "landmark", time, the residual time distribution for an individual,
conditional on their updated marker values, can be used to produce a dynamic
prediction. To satisfy a consistency condition that links dynamic predictions at
different time points, the residual time distribution must follow from a
prediction function that models the joint distribution of the marker process and
time to failure, such as a joint model. To circumvent the assumptions and
computational burden associated with a joint model, approximate methods for
dynamic prediction have been proposed. One such method is landmarking, which fits
a Cox model at a sequence of landmark times, and thus is not a comprehensive
probability model of the marker process and the event time. Considering an
illness-death model, we derive the residual time distribution and demonstrate
that the structure of the Cox model baseline hazard and covariate effects under
the landmarking approach do not have simple form. We suggest some extensions of
the landmark Cox model that should provide a better approximation. We compare the
performance of the landmark models with joint models using simulation studies and
cognitive aging data from the PAQUID study. We examine the predicted
probabilities produced under both methods using data from a prostate cancer
study, where metastatic clinical failure is a time-dependent covariate for
predicting death following radiation therapy.
PMID- 28508546
TI - Necrolytic migratory erythema associated with glucagonoma treated successfully
with cyclosporine.
PMID- 28508547
TI - Functional phosphatome requirement for protein homeostasis, networked
mitochondria, and sarcomere structure in C. elegans muscle.
AB - BACKGROUND: Skeletal muscle is central to locomotion and metabolic homeostasis.
The laboratory worm Caenorhabditis elegans has been developed into a genomic
model for assessing the genes and signals that regulate muscle development and
protein degradation. Past work has identified a receptor tyrosine kinase
signalling network that combinatorially controls autophagy, nerve signal to
muscle to oppose proteasome-based degradation, and extracellular matrix-based
signals that control calpain and caspase activation. The last two discoveries
were enabled by following up results from a functional genomic screen of known
regulators of muscle. Recently, a screen of the kinome requirement for muscle
homeostasis identified roughly 40% of kinases as required for C. elegans muscle
health; 80 have identified human orthologues and 53 are known to be expressed in
skeletal muscle. To complement this kinome screen, here, we screen most of the
phosphatases in C. elegans. METHODS: RNA interference was used to knockdown
phosphatase-encoding genes. Knockdown was first conducted during development with
positive results also knocked down only in fully developed adult muscle. Protein
homeostasis, mitochondrial structure, and sarcomere structure were assessed using
transgenic reporter proteins. Genes identified as being required to prevent
protein degradation were also knocked down in conditions that blocked proteasome
or autophagic degradation. Genes identified as being required to prevent
autophagic degradation were also assessed for autophagic vesicle accumulation
using another transgenic reporter. Lastly, bioinformatics were used to look for
overlap between kinases and phosphatases required for muscle homeostasis, and the
prediction that one phosphatase was required to prevent mitogen-activated protein
kinase activation was assessed by western blot. RESULTS: A little over half of
all phosphatases are each required to prevent abnormal development or maintenance
of muscle. Eighty-six of these phosphatases have known human orthologues, 57 of
which are known to be expressed in human skeletal muscle. Of the phosphatases
required to prevent abnormal muscle protein degradation, roughly half are
required to prevent increased autophagy. CONCLUSIONS: A significant portion of
both the kinome and phosphatome are required for establishing and maintaining C.
elegans muscle health. Autophagy appears to be the most commonly triggered form
of protein degradation in response to disruption of phosphorylation-based
signalling. The results from these screens provide measurable phenotypes for
analysing the combined contribution of kinases and phosphatases in a multi
cellular organism and suggest new potential regulators of human skeletal muscle
for further analysis.
PMID- 28508548
TI - A prospective evaluation of methylene blue and gentian violet dressing for
management of chronic wounds with local infection.
AB - The objective of this prospective, non-randomised study was to evaluate the
performance of an antibacterial foam dressing containing methylene blue and
gentian violet (Hydrofera Blue Classic dressing(r) ) for the management of
chronic wounds with local infection. Patients in this study were >=18 years of
age (n = 29), and each had at least one chronic wound >=1 cm2 in size that showed
signs of localised infection or critical colonisation but with good potential for
healing based on clinical assessment. To all of these wounds, the dressing was
applied and changed three times per week over the 4-week study period. The
primary endpoints of the study were: (i) changes in wound surface area
measurement, (ii) changes in Pressure Ulcer Scale for Healing (PUSH) scores,
(iii) changes in percent surface area of devitalised tissue (i.e., yellow slough
or other necrotic tissue) and (iv) changes in clinical signs associated with
localised wound infection/critical colonisation. Participants were evaluated at
presentation (week 0 = baseline), week 2 and at week 4 (end of the study). The 29
patients completed the study, and at week 4, the following wound improvements
were observed: (i) baseline mean wound surface area was significantly reduced by
42.5%, from 21.4 to 12.3 cm2 at week 4 (P = 0.005); (ii) baseline mean PUSH score
decreased significantly from 13.3 to 10.7 at week 4 (P < 0.001); (iii) baseline
mean wound coverage by devitalised tissue (%) was significantly reduced, from
52.6 % to 11.4% at week 4 (P < 0.001) and (iv) the mean UPPER and LOWER wound
infection scores were reduced from 3.6 at baseline to 0.9 at week 4 (75%; P <
0.001). These results indicate that the Hydrofera Blue Classic dressing was
effective at managing these chronic wounds and helped them progress onto a
healing trajectory.
PMID- 28508549
TI - Prenatal prediction of postnatal large-for-dates neonates using a simplified MRI
method: comparison with conventional 2D ultrasound estimates.
AB - OBJECTIVE: To evaluate the performance of a simple semi-automated method for
estimation of fetal weight (EFW) using magnetic resonance imaging (MRI) as
compared with two-dimensional (2D) ultrasound (US) for the prediction of large
for-dates neonates. METHODS: Data of two groups of women with singleton pregnancy
between March 2011 and May 2016 were retrieved from our database and evaluated
retrospectively: the first group included women who underwent US-EFW and MRI-EFW
within 48 h before delivery and the second group included women who had these
evaluations between 35 + 0 weeks and 37 + 6 weeks of gestation, more than 48 h
before delivery. US-EFW was based on Hadlock et al. and MRI-EFW on the formula
described by Baker et al. For MRI-EFW, planimetric measurement of the fetal body
volume (FBV) was performed using a semi-automated method and the time required
for measurement was noted. Outcome measure was the performance of MRI-EFW vs US
EFW in the prediction of large-for-dates neonates, both <= 48 h and > 48 h before
delivery. Receiver-operating characteristics (ROC) curves for each method were
compared using the DeLong method. RESULTS: Of the 270 women included in the first
group, 48 (17.8%) newborns had birth weight >= 90th centile and 30 (11.1%) >=
95th centile. The second group included 83 women, and nine (10.8%) newborns had
birth weight >= 95th centile. Median time needed for FBV planimetric measurements
in all 353 fetuses was 3.5 (range, 1.5-5.5) min. The area under the ROC curve
(AUC) for prediction of large-for-dates neonates by prenatal MRI performed within
48 h before delivery was significantly higher than that by US (for birth weight
>= 90th centile, difference between AUCs = 0.085, standard error (SE) = 0.020, P
< 0.001; for birth weight >= 95th centile, difference between AUCs = 0.036, SE =
0.014, P = 0.01). Similarly, MRI-EFW was better than US-EFW in predicting birth
weight >= 95th centile when both examinations were performed > 48 h prior to
delivery (difference between AUCs = 0.077, SE = 0.039, P = 0.045). CONCLUSION:
MRI planimetry using our purpose-designed semi-automated method is not time
consuming. The predictive performance of MRI-EFW performed immediately prior to
or remote from delivery is significantly better than that of US-EFW for the
prediction of large-for-dates neonates. Copyright (c) 2017 ISUOG. Published by
John Wiley & Sons Ltd.
PMID- 28508550
TI - Photoluminescent Peptide-Based Nanostructures as FRET Donor for Fluorophore Dye.
AB - A great interest has been recently generated by the discovery that peptide-based
nanostructures (NSs) endowed with cross-beta structure may show interesting
photoluminescent (PL) properties. It was shown that NSs formed by PEGylated
hexaphenylalanine (PEG8 -F6, PEG=polyethylene glycol) are able to emit at 460 nm
when excited at 370 or 410 nm. Here, the possibility to transfer the fluorescence
of these PEG8 -F6-based NSs by foster resonance electron transfer (FRET)
phenomenon to a fluorescent dye was explored. To achieve this aim, the 4-chloro-7
nitrobenzofurazan (NBD) dye was encapsulated in these NSs. Structural data in
solution and in solid state, obtained by a variety of techniques (circular
dichroism, Fourier-transform infrared spectroscopy, wide-angle X-ray scattering,
and small-angle X-ray scattering), indicated that the organization of the peptide
spine of PEG8 -F6 NS, which consists of anti-parallel beta-sheets separated by a
dry interface made of interacting phenylalanine side chains, was maintained upon
NBD encapsulation. The spectroscopic characterization of these NSs clearly showed
a red-shift of the emission fluorescence peak both in solution and in solid
state. This shift from 460 to 530 nm indicated that a FRET phenomenon from the
peptide-based to the fluorophore-encapsulated NS occurred. FRET could also be
detected in the PEG8 -F6 conjugate, in which the NBD was covalently bound to the
amine of the compound. On the basis of these results, it is suggested that the
red-shift of the intrinsic PL of NSs may be exploited in the bio-imaging field.
PMID- 28508551
TI - First study of mtDNA (D-loop) in Brazilian Caipira chickens.
PMID- 28508552
TI - Real-Time Analysis of Folding upon Binding of a Disordered Protein by Using
Dissolution DNP NMR Spectroscopy.
AB - The kinase inhibitory domain of the cell cycle regulatory protein p27Kip1 (p27)
was nuclear spin hyperpolarized using dissolution dynamic nuclear polarization (D
DNP). While intrinsically disordered in isolation, p27 adopts secondary
structural motifs, including an alpha-helical structure, upon binding to cyclin
dependent kinase 2 (Cdk2)/cyclin A. The sensitivity gains obtained with
hyperpolarization enable the real-time observation of 13 C NMR signals during p27
folding upon binding to Cdk2/cyclin A on a time scale of several seconds. Time
dependent intensity changes are dependent on the extent of folding and binding,
as manifested in differential spin relaxation. The analysis of signal decay rates
suggests the existence of a partially folded p27 intermediate during the
timescale of the D-DNP NMR experiment.
PMID- 28508555
TI - Laminin and collagen IV inclusion in immunoisolating microcapsules reduces
cytokine-mediated cell death in human pancreatic islets.
AB - Extracellular matrix (ECM) molecules have several functions in pancreatic islets,
including provision of mechanical support and prevention of cytotoxicity during
inflammation. During islet isolation, ECM connections are damaged, and are not
restored after encapsulation and transplantation. Inclusion of specific
combinations of collagen type IV and laminins in immunoisolating capsules can
enhance survival of pancreatic islets. Here we investigated whether ECM can also
enhance survival and lower susceptibility of human islets to cytokine-mediated
cytotoxicity. To this end, human islets were encapsulated in alginate with
collagen IV and either RGD, LRE or PDSGR, i.e. laminin sequences. Islets in
capsules without ECM served as control. The encapsulated islets were exposed to
IL-1beta, IFN-gamma and TNF-alpha for 24 and 72 h. All combinations of ECM
improved the islet cell survival, and reduced necrosis and apoptosis after
cytokine exposure (P < 0.01). Collagen IV-RGD and collagen IV-LRE reduced danger
associated molecular patterns (DAMPs) release from islets (P < 0.05). Moreover,
collagen IV-RGD and collagen IV-PDSGR, but not collagen IV-LRE, reduced NO
release from encapsulated human islets (P < 0.05). This reduction correlated with
a higher oxygen consumption rate (OCR) of islets in capsules containing collagen
IV-RGD and collagen IV-PDSGR. Islets in capsules with collagen IV-LRE showed more
dysfunction, and OCR was not different from islets in control capsules without
ECM. Our study demonstrates that incorporation of specific ECM molecules such as
collagen type IV with the laminin sequences RGD and PDSGR in immunoisolated
islets can protect against cytokine toxicity.
PMID- 28508553
TI - A targeted proteomic assay for the measurement of plasma proteoforms related to
human aging phenotypes.
AB - Circulating polypeptides and proteins have been implicated in reversing or
accelerating aging phenotypes, including growth/differentiation factor 8 (GDF8),
GDF11, eotaxin, and oxytocin. These proteoforms, which are defined as the protein
products arising from a single gene due to alternative splicing and PTMs, have
been challenging to study. Both GDF8 and GDF11 have known antagonists such as
follistatin (FST), and WAP, Kazal, immunoglobulin, Kunitz, and NTR domain
containing proteins 1 and 2 (WFIKKN1, WFIKKN2). We developed a novel multiplexed
SRM assay using LC-MS/MS to measure five proteins related to GDF8 and GDF11
signaling, and in addition, eotaxin, and oxytocin. Eighteen peptides consisting
of 54 transitions were monitored and validated in pooled human plasma. In 24
adults, the mean (SD) concentrations (ng/mL) were as follows: GDF8 propeptide,
11.0 (2.4); GDF8 mature protein, 25.7 (8.0); GDF11 propeptide, 21.3 (10.9); GDF11
mature protein, 16.5 (12.4); FST, 29.8 (7.1); FST cleavage form FST303, 96.4
(69.2); WFIKKN1, 38.3 (8.3); WFIKKN2, 32.2 (10.5); oxytocin, 1.9 (0.9); and
eotaxin, 2.3 (0.5). This novel multiplexed SRM assay should facilitate the study
of the relationships of these proteoforms with major aging phenotypes.
PMID- 28508554
TI - Intestinal epithelial suppressor of cytokine signaling 3 (SOCS3) impacts on
mucosal homeostasis in a model of chronic inflammation.
AB - INTRODUCTION: Suppressor of cytokine signaling 3 (SOCS3) is a tumour suppressor,
limiting intestinal epithelial cell (IEC) proliferation in acute inflammation,
and tumour growth, but little is known regarding its role in mucosal homeostasis.
Resistance to the intestinal helminth Trichuris muris relies on an "epithelial
escalator" to expel the parasite. IEC turnover is restricted by parasite-induced
indoleamine 2,3-dioxygenase (IDO). METHODS: Mice with or without conditional
knockout of SOCS3 were infected with T. muris. Crypt depth, worm burden, and
proliferating cells and IDO were quantified. SOCS3 knockdown was also performed
in human IEC cell lines. RESULTS: Chronic T. muris infection increased expression
of SOCS3 in wild-type mice. Lack of IEC SOCS3 led to a modest increase in
epithelial turnover. This translated to a lower worm burden, but not complete
elimination of the parasite suggesting a compensatory mechanism, possibly IDO, as
seen in SOCS3 knockdown. CONCLUSIONS: We report that SOCS3 impacts on IEC
turnover following T. muris infection, potentially through enhancement of IDO.
IDO may dampen the immune response which can drive IEC hyperproliferation in the
absence of SOCS3, demonstrating the intricate interplay of immune signals
regulating mucosal homeostasis, and suggesting a novel tumour suppressor role of
SOCS3.
PMID- 28508556
TI - Impact of co-morbidities on resource use and adherence to guidelines among
commercially insured adults with new visits for back pain.
AB - RATIONALE, AIMS AND OBJECTIVES: To assess if co-morbidity is associated with
higher use of back-related care and adherence to back pain guidelines. METHODS:
We conducted a retrospective cohort study using administrative claims data from
2007-2011. We included individuals >=18 years with an index visit for back pain.
Co-morbidities were measured 12 months prior to index. Co-morbidity burden was
measured using Quan's Co-morbidity Index. Co-morbidities categories were measured
using chronic condition indicators from the Agency for Healthcare Research and
Quality. Total lumbar spine-related resource use for three years was ascertained
using procedure codes. A clustering algorithm identified higher long-term
utilizer. We identified initial use from day 0-42 for several categories of spine
related care. We used logistic regression to test the association between co
morbidities and resource use. RESULTS: Greater co-morbidity burden was associated
with higher long-term spine-related resource use. Those with >=2 on Quan's Co
morbidity Index had 29% higher odds of being a high back-specific resource user
compared to those with no co-morbidities [Odds Ratio (OR): 1.29, 95% Confidence
Interval (CI): 1.23-1.35]. Greater co-morbidity burden was associated with more
frequent initial use of imaging, emergency visits, injections, and opioid fills;
and less frequent initial use of medical and physical therapy visits. Co-morbid
musculoskeletal conditions had the strongest association with being a high
utilizer of long-term back-specific resources (OR: 1.53, 95% CI: 1.50-1.57).
CONCLUSIONS: Co-morbidity burden and the presence of specific chronic conditions,
such as musculoskeletal conditions, were associated with high long-term use of
back-related care and care inconsistent with guidelines.
PMID- 28508557
TI - LOPP chemotherapy as a first-line treatment for dogs with T-cell lymphoma.
AB - BACKGROUND: The aim of this study was to describe the use of a lomustine (CCNU),
vincristine, procarbazine and prednisolone (LOPP) protocol used for treatment of
chemotherapy naive T-cell lymphoma patients and to describe the response rate,
toxicity and disease-free interval compared historically to CHOP chemotherapy.
MATERIALS AND METHODS: Retrospective case study of 31 dogs with naive T-cell
lymphoma treated with a lomustine (CCNU), vincristine, procarbazine and
prednisolone (LOPP) protocol. RESULTS: Thirty-one dogs with T cell lymphoma were
treated. The overall response rate was 97%. Of the 30 dogs that had a response to
LOPP chemotherapy, the median disease free interval was 176 days (range 0-1745
days). The median overall survival time for this study group was 323 days (range
51-1758 days). All deaths in this study were attributable to lymphoma.
CONCLUSION: LOPP chemotherapy for T cell lymphoma is well tolerated with a low
toxicity profile and an excellent overall response rate. This protocol showed
minimal toxicity and comparable disease free interval and survival times for
canine high grade T cell lymphoma treated with CHOP.
PMID- 28508558
TI - Individual survival curves comparing subjective and observed mortality risks.
AB - We compare individual survival curves constructed from objective (actual
mortality) and elicited subjective information (probability of survival to a
given target age). We develop a methodology to estimate jointly subjective and
objective individual survival curves accounting for rounding on subjective
reports of perceived survival. We make use of the long follow-up period in the
Health and Retirement Study and the high quality of mortality data to estimate
individual survival curves that feature both observed and unobserved
heterogeneity. This allows us to compare objective and subjective estimates of
remaining life expectancy for various groups and compare welfare effects of
objective and subjective mortality risk using the life cycle model of
consumption. We find that subjective and objective hazards are not the same. The
median welfare loss from misperceptions of mortality risk when annuities are not
available is 7% of current wealth at age 65 whereas more than 25% of respondents
have losses larger than 60% of wealth. When annuities are available and
exogenously given, the welfare loss is substantially lower.
PMID- 28508559
TI - Two weeks of repetitive gut-challenge reduce exercise-associated gastrointestinal
symptoms and malabsorption.
AB - Debilitating gastrointestinal symptoms is a common feature of endurance running
and may be exacerbated by and/or limit the ability to tolerate carbohydrate
intake during exercise. The study aimed to determine whether two weeks of
repetitive gut-challenge during running can reduce exercise-associated
gastrointestinal symptoms and carbohydrate malabsorption. Endurance runners
(n=18) performed an initial gut-challenge trial (GC1) comprising 2-hour running
exercise at 60% VO2max (steady state) while consuming a formulated gel-disk
containing 30 g carbohydrates (2:1 glucose-fructose, 10% w/v) every 20 minutes,
followed by a 1-hour running effort bout. Gastrointestinal symptoms, feeding
tolerance, and breath hydrogen (H2 ) were determined along the gut-challenge
trial. After GC1, participants were randomly assigned to a blinded carbohydrate
(CHO, 90 gCHO hour-1 ) or placebo (PLA, 0 gCHO hour-1 ) gut-training group. This
comprised of consuming the group-specific feeding intervention during 1-hour
running exercise at 60% VO2max equivalent, daily over a period of two weeks.
Participants then repeated the gut-challenge trial (GC2). In GC2, a reduced gut
discomfort (P=.012), total (P=.009), upper- (P=.015), and lower-gastrointestinal
(P=.008) symptoms, and nausea (P=.05) were observed on CHO, but not PLA. Feeding
tolerance did not differ between GC1 and GC2 on CHO and PLA. H2 peak was
attenuated in GC2 (6+/-3 ppm) compared to GC1 (13+/-6 ppm) on CHO (P=.004), but
not on PLA (GC1 11+/-7 ppm, and GC2 10+/-10 ppm). The effort bout distance was
greater in GC2 (12.3+/-1.3 km) compared with GC1 (11.7+/-1.5 km) on CHO (P=.035)
only. Two weeks of repetitive gut-challenge improve gastrointestinal symptoms and
reduce carbohydrate malabsorption during endurance running, which may have
performance implications.
PMID- 28508560
TI - Anionic Regulated NiFe (Oxy)Sulfide Electrocatalysts for Water Oxidation.
AB - The construction of active sites with intrinsic oxygen evolution reaction (OER)
is of great significance to overcome the limited efficiency of abundant
sustainable energy devices such as fuel cells, rechargeable metal-air batteries,
and in water splitting. Anionic regulation of electrocatalysts by modulating the
electronic structure of active sites significantly promotes OER performance. To
prove the concept, NiFeS electrocatalysts are fabricated with gradual variation
of atomic ratio of S:O. With the rise of S content, the overpotential for water
oxidation exhibits a volcano plot under anionic regulation. The optimized NiFeS-2
electrocatalyst under anionic regulation possesses the lowest OER overpotential
of 286 mV at 10 mA cm-2 and the fastest kinetics being 56.3 mV dec-1 to date. The
anionic regulation methodology not only serves as an effective strategy to
construct superb OER electrocatalysts, but also enlightens a new point of view
for the in-depth understanding of electrocatalysis at the electronic and atomic
level.
PMID- 28508561
TI - Diclofenac for pain associated with intravitreal injections: a prospective,
randomized, placebo-controlled study.
AB - IMPORTANCE: Intravitreal injections (IVI) are often painful. BACKGROUND: To
evaluate the analgesic effect of diclofenac in patients undergoing IVI. DESIGN:
Single-centre, prospective, randomized, triple-arm, placebo-controlled,
interventional study in the University Hospital of Patras. PARTICIPANTS: Seventy
four patients. METHODS: Group 1 (n = 25) received topical diclofenac 45 min
before IVI, Group 2 (n = 25) received oral diclofenac 4 h before IVI and topical
diclofenac while Group 3 (n = 24) received placebo before IVI. Using the short
form of the McGill Pain Questionnaire (SF-MPQ), pain intensity was assessed with
the visual analogue scale (VAS), the main component of the SF-MPQ and the Present
Pain Intensity (PPI) scores immediately and 6 h post-IVI. MAIN OUTCOME MEASURES:
The VAS pain score immediately post-IVI. RESULTS: Immediately post-IVI, patients
in Group 2 reported significantly lower VAS pain scores compared to placebo while
no statistically significant difference was found between patients that received
topical diclofenac and placebo. Six hours post-IVI, patients in both treatment
groups reported significant lower VAS pain scores compared to placebo. The scores
of the main component of the SF-MPQ were significantly lower in patients of
treatment groups compared to placebo at both time-points. Finally, while no
statistically significant difference was found between the 3 Groups in PPI scores
immediately post-IVI, 6 h later, patients of both treatment groups reported
significantly lower PPI scores compared to placebo. CONCLUSIONS AND RELEVANCE:
The combination of topical and oral diclofenac demonstrated better analgesic
effect than topical diclofenac administration in patients undergoing IVI
immediately and up to 6 h post-IVI.
PMID- 28508562
TI - Can serological methods help distinguish between prophylactic and alloimmune anti
D?
AB - OBJECTIVES: Enzyme indirect antiglobulin test (EIAT) and polyethylene glycol IAT
(PIAT) were evaluated for their potential use as tests to distinguish between
prophylactic and alloimmune anti-D in plasma by comparing with a tube variation
of the standard low ionic strength solution-IAT (LISS-IAT). BACKGROUND:
Laboratories performing the screening of RhD-negative pregnant women are required
to provide clinicians with guidance as to the source of detected RhD antibodies.
Currently, this is derived from RhIg immunoprophylaxis history, agglutination
scores and titration results, where performed. A serological test that can
differentiate between prophylactic and alloimmune anti-D would be useful in the
diagnosis of RhD alloimmunisation in pregnant women. MATERIALS AND METHODS:
Plasma samples (n = 273) [fresh (collected from April 2014 to February 2015) and
frozen (up to 2 years)] from antenatal females, preoperative males and females
over child-bearing age were used in this study. Samples were identified as
containing anti-D by routine column agglutination (CAT) and were tested by tube
LISS-IAT, EIAT and PIAT, and a score difference was calculated. RESULTS: A total
of 32% of alloimmune anti-D samples demonstrated an increase in agglutination
score (+2 or +3) when tested by EIAT. A significant increase in agglutination
score for alloimmune samples using EIAT compared with LISS-IAT was observed. EIAT
had a sensitivity (Sn) of 59%, positive predictive value (PPV) of 100% and
specificity (Sp) of 100% for alloimmune anti-D. CONCLUSION: EIAT is capable of
confirming but not excluding the presence of alloimmune anti-D in samples where
anti-D is detected in routine antibody screening.
PMID- 28508563
TI - Safety Aspects of Immunoadsorption in IgG Removal Using a Single-Use, Multiple
pass Protein A Immunoadsorber (LIGASORB): Clinical Investigation in Healthy
Volunteers.
AB - Therapeutic apheresis and immunoadsorption are used to deplete efficiently
pathogenic autoantibodies in crises in several acute autoimmune driven diseases.
This prospective, non-comparative cohort study was conducted at a single study
center under standardized conditions in 10 healthy volunteers. Efficient
immunoglobulin G (IgG) removal (-86% versus baseline) was achieved after 3
apheresis treatments on 3 consecutive days. The treatments were well tolerated.
Safety laboratory parameters did not show unexpected or pathological changes. The
effects were transient, with most parameters exhibiting complete recovery between
treatments. Minimal complement activation and moderate transient fibrinogen
depletion were observed. Immunoadsorption with LIGASORB(r) provides a safe and
effective treatment alternative to TPE in acute episodes of peripheral
neurological diseases mediated by pathogenic IgG autoantibodies.
PMID- 28508564
TI - Enantioselective Borylation of Aromatic C-H Bonds with Chiral Dinitrogen Ligands.
AB - The borylation of C-H bonds catalyzed by transition metals has been investigated
extensively in the past two decades, but no iridium-catalyzed enantioselective
borylation of C-H bonds has been reported. We report a set of iridium-catalyzed
enantioselective borylations of aromatic C-H bonds. This reaction relies on a set
of newly developed chiral quinolyl oxazoline ligands. This process proceeds under
mild conditions with good to excellent enantioselectivity, and the borylated
products can be converted to enantioenriched derivatives containing new C-O, C-C,
C-Cl, or C-Br bonds.
PMID- 28508565
TI - Menaquinone-4 enhances osteogenic potential of human amniotic fluid mesenchymal
stem cells cultured in 2D and 3D dynamic culture systems.
AB - Menaquinones, also known as Vitamin K2 family, regulate calcium homeostasis in a
'bone-vascular cross-talk' and recently received particular attention for their
positive effect on bone formation. Given that the correlation between
menaquinones and bone metabolism to date is still unclear, the objective of our
study was to investigate the possible role of menaquinone-4 (MK-4), an isoform of
the menaquinones family, in the modulation of osteogenesis. For this reason, we
used a model of human amniotic fluid mesenchymal stem cells (hAFMSCs) cultured
both in two-dimensional (2D) and three-dimensional (3D; RCCSTMbioreactor) in
vitro culture systems. Furthermore, to mimic the 'bone remodelling unit' in
vitro, hAFMSCs were co-cultured in the 3D system with human monocyte cells (hMCs)
as osteoclast precursors. The results showed that in a conventional 2D culture
system, hAFMSCs were responsive to the MK-4, which significantly improved the
osteogenic process through gamma-glutamyl carboxylase-dependent pathway. The same
results were obtained in the 3D dynamic system where MK-4 treatment supported the
osteoblast-like formation promoting the extracellular bone matrix deposition and
the expression of the osteogenic-related proteins (alkaline phosphatase,
osteopontin, collagen type-1 and osteocalcin). Notably, when the hAFMSCs were co
cultured in a 3D dynamic system with the hMCs, the presence of MK-4 supported the
cellular aggregate formation as well as the osteogenic function of hAFMSCs, but
negatively affected the osteoclastogenic process. Taken together, our results
demonstrate that MK-4 supported the aggregate formation of hAFMSCs and increased
the osteogenic functions. Specifically, our data could help to optimize bone
regenerative medicine combining cell-based approaches with MK-4 treatment.
PMID- 28508566
TI - Initial observation of CIN2 does not appear to reduce quality of life in women
under 25 years of age.
AB - BACKGROUND: Although the patient perspective is implicit in the practice of
medicine, research evaluating this remains scarce. In a climate where clinicians
and policy-makers constantly strive to achieve more patient-centred models of
care, this omission warrants attention. AIM: To assess health-related quality of
life (HrQoL) in women under 25 years of age with cervical intra-epithelial
neoplasia grade 2 (CIN2) receiving conservative management (colposcopy follow-up,
with treatment if necessary) compared with those receiving immediate excisional
treatment with large loop excision of the transformation zone (LLETZ). METHODS:
An observational study evaluating HrQoL was conducted at Christchurch Women's
Hospital, New Zealand. Women undergoing conservative management for CIN2 were
compared with those undergoing immediate excisional treatment in an age-matched
sample. The Short Form Health Survey 12 version 2 (SF-12v2) was used to evaluate
HrQoL. Secondary outcomes of anxiety and sexual function were also assessed.
RESULTS: One hundred and four women with CIN2 participated in the study. Of
these, 63 (60%) received conservative management and 41 (40%) received immediate
excisional treatment with LLETZ. We found no significant difference in HrQoL
between the groups in a multivariate regression analysis adjusted for parity,
smoking and socioeconomic status. There were also no significant differences in
sexual function or anxiety. CONCLUSION: We found no difference in HrQoL by
management strategy. Conservative management of CIN2 in women under 25 is
unlikely to have an adverse impact on self-reported HrQoL, anxiety or sexual
functioning compared with conventional management.
PMID- 28508567
TI - P Doped MoO3-x Nanosheets as Efficient and Stable Electrocatalysts for Hydrogen
Evolution.
AB - A P doped MoO3-x nanocomposite material with rich oxygen vacancies is
successfully fabricated by a two-step intercalation method, which presents
superior activity for the hydrogen evolution reaction with low overpotential and
fast electron transfer. In 0.5 m H2 SO4 , it displays an overpotential of 166 mV
for driving the current density of 10 mA cm-2 . Moreover, it also shows a good
catalytic stability in the electrolytes with different pH, 0.5 m H2 SO4 (strong
acid), 0.5 m Na2 SO4 (neutral solution), and 0.1 m NaOH (strong base). The
superior catalytic activity and stability are due to to the synergistic effect
between the P element doping and the oxygen vacancies.
PMID- 28508568
TI - Randomized crossover trial of a pressure sensing visual feedback system to
improve mask fitting in noninvasive ventilation.
AB - BACKGROUND AND OBJECTIVE: A good mask fit, avoiding air leaks and pressure
effects on the skin are key elements for a successful noninvasive ventilation
(NIV). However, delivering practical training for NIV is challenging, and it
takes time to build experience and competency. This study investigated whether a
pressure sensing system with real-time visual feedback improved mask fitting.
METHODS: During an NIV training session, 30 healthcare professionals (14 trained
in mask fitting and 16 untrained) performed two mask fittings on the same healthy
volunteer in a randomized order: one using standard mask-fitting procedures and
one with additional visual feedback on mask pressure on the nasal bridge.
Participants were required to achieve a mask fit with low mask pressure and
minimal air leak (<10 L/min). Pressure exerted on the nasal bridge, perceived
comfort of mask fit and staff- confidence were measured. RESULTS: Compared with
standard mask fitting, a lower pressure was exerted on the nasal bridge using the
feedback system (71.1 +/- 17.6 mm Hg vs 63.2 +/- 14.6 mm Hg, P < 0.001). Both
untrained and trained healthcare professionals were able to reduce the pressure
on the nasal bridge (74.5 +/- 21.2 mm Hg vs 66.1 +/- 17.4 mm Hg, P = 0.023 and 67
+/- 12.1 mm Hg vs 60 +/- 10.6 mm Hg, P = 0.002, respectively) using the feedback
system and self-rated confidence increased in the untrained group. CONCLUSION:
Real-time visual feedback using pressure sensing technology supported healthcare
professionals during mask-fitting training, resulted in a lower pressure on the
skin and better mask fit for the volunteer, with increased staff confidence.
PMID- 28508569
TI - Regulatory T cell signatures in liver transplant recipients successfully weaned
from immunosuppression: Getting from here to there.
PMID- 28508571
TI - Commentary on: Pratt SS, Losier BJ, Moulden HM, Chaimowitz GA. Incapacity of the
mind secondary to medication misuse as a not criminally responsible defense. J
Forensic Sci 2017;62(1):267-9.
PMID- 28508570
TI - A new transcript in the TCRB locus unveils the human ortholog of the mouse pre
Dbeta1 promoter.
AB - INTRODUCTION: While most transcripts arising from the human T Cell Receptor locus
reflect fully rearranged genes, several germline transcripts have been
identified. We describe a new germline transcript arising from the human TCRB
locus. METHODS: cDNA sequencing, promoter, and gene expression analyses were used
to characterize the new transcript. RESULTS: The new germline transcript encoded
by the human TCRB locus consists of a new exon of 103 bp, which we named TRBX1
(X1), spliced with the first exon of gene segments Cbeta1 or Cbeta2. X1 is
located upstream of gene segment Dbeta1 and is therefore deleted from a V-DJ
rearranged TCRB locus. The X1-Cbeta transcripts do not appear to code for a
protein. We define their transcription start and minimal promoter. These
transcripts are found in populations of mature T lymphocytes from blood or
tissues and in T cell clones with a monoallelic TCRB rearrangement. In immature
thymocytes, they are already detectable in CD1a- CD34+ CD4- CD8- cells, therefore
before completion of the TCRB rearrangements. CONCLUSIONS: The X1 promoter
appears to be the ortholog of the mouse pre-Dbeta1 promoter (PDbeta1). Like
PDbeta1, its activation is regulated by Ebeta in T cells and might facilitate the
TCRB rearrangement process by contributing to the accessibility of the Dbeta1
locus.
PMID- 28508572
TI - Clinical characteristics and factors associated with mortality in idiopathic
pulmonary fibrosis: An experience from a tertiary care center in Pakistan.
AB - INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive
interstitial lung disease (ILD) that predominantly affects older adults. IPF has
the highest mortality burden of all ILDs. Data on mortality in patients with IPF
is limited in developing countries. OBJECTIVES: To identify factors associated
with mortality in patients with IPF at a tertiary care center in Pakistan.
METHODS: A retrospective chart review was conducted at the Aga Khan University
Hospital (AKUH) in Karachi, Pakistan from January 2005 to December 2015. Patients
were assessed for smoking status, clinical onset of disease, pulmonary
hypertension, disease severity based on spirometry and hypoxemia. RESULTS: A
total of 239 cases were reviewed, of which 103 were non-survivors. A total of 45
(18%) were current smokers and 71 (29.7%) were ex-smokers. Smoking was more
common in non-survivors (56.3% P <= .01). Pulmonary hypertension was present in
18.8% of patients. 95.4% of patients who had received pirfenidone treatment were
alive at the time of study. On multivariate analysis, pirfenidone treatment (OR
0.03; 95% CI 0.01-0.08), current smoking (OR 2.60; 95% CI 1.04-6.58), age older
than 60 years (OR 2.63; 95% CI 1.04-6.58) and hypoxemia (OR 3.29; 95% CI 1.58
6.84) were the factors associated with mortality. CONCLUSION: Smoking, age
greater than 60 years and hypoxemia were identified as factors that increased the
odds of mortality in IPF patients, whereas pirfenidone was found to lower the
odds of mortality.
PMID- 28508574
TI - Isomer-Selective Generation and Spectroscopic Characterization of Picolyl
Radicals.
AB - Nitrogen-containing resonance-stabilized radicals such as the picolyl radical are
important in combustion chemistry and astrochemistry. They have only been
scarcely studied because an isomer-selective generation is often difficult.
Herein, we present threshold photoelectron spectra of the three picolyl radical
isomers, C6 H6 N, that were obtained with synchrotron radiation. The radicals
were selectively generated by flash pyrolysis from aminomethylpyridine precursors
through deamination. Ionization energies of 7.70, 7.59, and 8.01 eV were
determined for 2-, 3-, and 4-picolyl, respectively. The observed vibrational
structure was assigned to an in-plane deformation mode of the aromatic ring. The
spectroscopic insight gained in this study can be used to distinguish different
picolyl isomers in on-line combustion analysis, for example.
PMID- 28508573
TI - Regional differences in the management and outcome of kidney transplantation in
patients with human immunodeficiency virus infection: A 3-year retrospective
cohort study.
AB - BACKGROUND: In the developed world, kidney transplantation (KT) in patients with
human immunodeficiency virus (HIV) infection is well established. Developing
countries concentrate 90% of the people living with HIV, but their experience is
underreported. Regional differences may affect outcomes. OBJECTIVES: We compared
the 3-year outcomes of patients with HIV infection receiving a KT in two
different countries, in terms of incomes and development. METHODS: This was an
observational, retrospective, double-center study, including all HIV-infected
patients >18 years old undergoing KT. RESULTS: Between 2005 and 2015, 54 KTs were
performed (39 in a Brazilian center, and 15 in a Spanish center). Brazilians had
less hepatitis C virus co-infection (5% vs 27%, P=.024). Median cold ischemia
time was higher in Brazil (25 vs 18 hours, P=.001). Biopsy-proven acute rejection
(AR) was higher in Brazil (33% vs 13%, P=.187), as were the number of AR episodes
(22 vs 4, P=.063). Patient survival at 3 years was 91.3% in Brazil and 100% in
Spain; P=.663. All three cases of death in Brazil were a result of bacterial
infections within the first year post transplant. At 3 years, survival free from
immunosuppressive changes was lower in Brazil (56% vs 90.9%, P=.036). Raltegravir
based treatment to avoid interaction with calcineurin inhibitor was more
prevalent in Spain (80% vs 3%; P<.001). HIV infection remained under control in
all patients, with undetectable viral load and no opportunistic infections.
CONCLUSION: Important regional differences exist in the demographics and
management of immunosuppression and antiretroviral therapy. These details may
influence AR and infectious complications. Non-AIDS infections leading to early
mortality in Brazil deserve special attention.
PMID- 28508575
TI - Upregulation of inflammatory mediators in the ventricular zone after cortical
stroke.
AB - PURPOSE: After cortical stroke, neural precursor cells (NPCs) in the distal
ventricular zone (VZ) proliferate more rapidly and migrate toward the injured
cortex. While evidence suggests this can enhance stroke recovery, the underlying
molecular mechanisms initiating the response are poorly understood. Here we
identified changes in protein expression in the ipsilateral VZ early (4 h) after
stroke to gain insight into the initial mechanisms involved in NPC activation
post-stroke. EXPERIMENTAL DESIGN: Four hours after photothrombotic stroke (or
sham surgery control) in the sensorimotor cortex, adult mice (10 stroke, 10 sham)
were subjected to cardiac perfusion with PBS, and ipsilateral and contralateral
VZ tissue was microdissected. Two separate sets of ipsilateral and contralateral
VZ tissues (from 5 pooled surgery or 5 pooled sham mice) were analyzed
simultaneously using 8-plex iTRAQ. We used Western blotting and confocal
microscopy to confirm changes in protein expression in the VZ ipsilateral to
stroke in a separate cohort of mice. RESULTS: We identified nine proteins which
exhibited a significant mean increase (by >= 2-fold) in stroke ipsilateral
compared to sham ipsilateral. Many of these proteins were antiproteases or
cytokine/growth factor binding proteins that are known to act as inflammatory
responders or effectors and play roles in modulating tissue growth and
remodeling. CONCLUSION AND CLINICAL RELEVANCE: These novel findings support a
growing body of literature that inflammatory signaling is involved in the NPC
response to brain injury and identifies novel potential targets that could be
exploited to better understand and to optimize this regenerative response.
PMID- 28508577
TI - Intrinsic Notch Effect Leads to Breakdown of Griffith Criterion in Graphene.
AB - Due to lack of the third dimension in 3D bulk materials, the crack tip in
graphene locates on several atoms implying that its fracture behavior can be
closely associated with its lattice structure, i.e., the bond length and angle.
As the bond length reflects the discrete nature of the atomic structure,
theoretical discussion is focused on the concomitant size effect at the nanoscale
with few or no reports about the influence of the bond angle. Through the
comparisons between theoretical calculations and experimental data, here it is
first demonstrated that the bond angle is essential for understanding the
fracture behavior in graphene, serving as an intrinsic notch reducing the stress
singularity near the crack tip (the intrinsic notch effect), leading to the
breakdown of the Griffith criterion in graphene. The work provides a framework
for the studying of the brittle fracture in 2D materials, which gives rise to the
more reliable device design based on 2D materials. More importantly, the
significance of the intrinsic notch effect is profound and far-reaching, paving
the way to a more comprehensive and deep understanding of the mechanical
properties in nano as well as nanostructured materials.
PMID- 28508576
TI - MHC I presentation of Toxoplasma gondii immunodominant antigen does not require
Sec22b and is regulated by antigen orientation at the vacuole membrane.
AB - The intracellular Toxoplasma gondii parasite replicates within a parasitophorous
vacuole (PV). T. gondii secretes proteins that remain soluble in the PV space,
are inserted into PV membranes or are exported beyond the PV boundary. In
addition to supporting T. gondii growth, these proteins can be processed and
presented by MHC I for CD8+ T-cell recognition. Yet it is unclear whether
membrane binding influences the processing pathways employed and if topology of
membrane antigens impacts their MHC I presentation. Here we report that the MHC I
pathways of soluble and membrane-bound antigens differ in their requirement for
host ER recruitment. In contrast to the soluble SAG1-OVA model antigen, we find
that presentation of the membrane-bound GRA6 is independent from the SNARE
Sec22b, a key molecule for transfer of host endoplasmic reticulum components onto
the PV. Using parasites modified to secrete a transmembrane antigen with opposite
orientations, we further show that MHC I presentation is highly favored when the
C-terminal epitope is exposed to the host cell cytosol, which corresponds to GRA6
natural orientation. Our data suggest that the biochemical properties of antigens
released by intracellular pathogens critically guide their processing pathway and
are valuable parameters to consider for vaccination strategies.
PMID- 28508578
TI - Proteomic characterization of EL4 lymphoma-derived tumors upon chemotherapy
treatment reveals potential roles for lysosomes and caspase-6 during tumor cell
death in vivo.
AB - The murine mouse lymphoblastic lymphoma cell line (EL4) tumor model is an
established in vivo apoptosis model for the investigation of novel cancer imaging
agents and immunological treatments due to the rapid and significant response of
the EL4 tumors to cyclophosphamide and etoposide combination chemotherapy.
Despite the utility of this model system in cancer research, little is known
regarding the molecular details of in vivo tumor cell death. Here, we report the
first in-depth quantitative proteomic analysis of the changes that occur in these
tumors upon cyclophosphamide and etoposide treatment in vivo. Using a label-free
quantitative proteomic approach a total of 5838 proteins were identified in the
treated and untreated tumors, of which 875 were determined to change in abundance
with statistical significance. Initial analysis of the data reveals changes that
may have been predicted, such as the downregulation of ribosomes, but
demonstrates the robustness of the dataset. Analysis of the dataset also reveals
the unexpected downregulation of caspase-3 and an upregulation of caspase-6 in
addition to a global upregulation of lysosomal proteins in the bulk of the tumor.
PMID- 28508579
TI - Childhood obesity treatment: telephone coaching is as good as usual care in
maintaining weight loss - a randomized controlled trial.
AB - There is a need for more flexible treatment strategies to help patients reach
relevant treatment outcomes and adhere better to treatment. The aim of this study
was to evaluate the long-term efficacy, in terms of patients' weight status, of
replacing usual care (UC) physical visits with more frequent but shorter
telephone coaching (TC) sessions as part of a structured childhood obesity
treatment. In this controlled study, patients aged 5-14 years from the Sodertalje
outpatient clinic, Sweden were randomized to either UC or TC over an 18-month
period after participating in an initial standard obesity treatment programme.
The patients were followed for a mean of 3.7 years. In total, 37 children (UC, n
= 18 and TC, n = 19) were included, with a mean (standard deviation, SD) age of
9.5 (2.6) years and a body mass index standard deviation score (BMI SDS) of 2.9
(0.7). The change in BMI SDS did not differ between the groups during the study
(P = 0.8). Both groups had similar changes in BMI SDS 3.7 years after the first
visit to the clinic, TC = - 0.42 and UC = 0.52 BMI SDS units (P = 0.6 between
groups). There were no gender differences. Furthermore, the average time
clinicians spent with each patient during the study did not differ between the
groups (P = 0.5). No patients were lost to follow-up during the study. In
conclusion, the use of TC may offer greater flexibility in the treatment of
paediatric obesity as it was non-inferior for both treatment efficacy and the
time spent on treatment by healthcare personnel.
PMID- 28508582
TI - Conceptualizing behavioural addiction in children and adolescents.
PMID- 28508583
TI - Substrate-Specific Amino Acid Sensing Using a Molecular d/ l-Cysteine Probe for
Comprehensive Stereochemical Analysis in Aqueous Solution.
AB - The appearance of d-amino acids in mammals and humans has important implications
in the life sciences. d/l-Amino acid mixtures play a key role in human physiology
and pathology; thus, the introduction of artificial receptors for the real-time
quantification of both the concentration and d/l composition of amino acids is
very promising for the study of biological processes and for the diagnosis and
treatment of diseases. We now report a sensing assay that is compatible with
aqueous solutions and allows fast determination of the absolute configuration,
enantiomeric composition, and overall amount of cysteine at micromolar
concentrations. The method relies on fast UV and CD measurements, which provide
accurate stereochemical information on samples covering a wide concentration
range and drastically different d/l-cysteine ratios in simulated body fluids.
Competition experiments show that other amino acids and biothiols do not
interfere with the cysteine-targeted sensing.
PMID- 28508581
TI - Effect of under- and overfeeding on sheep and goat milk and plasma enzymes
activities related to oxidation.
AB - Twenty-four dairy sheep and goats, respectively, were assigned each to three
homogenous subgroups per animal species and fed the same diet in quantities which
met 70% (underfeeding), 100% (control) and 130% (overfeeding) of their energy and
crude protein requirements. The results showed that the underfed sheep in
comparison with the control had significantly lower glutathione reductase (GR),
superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX) activities
and total antioxidant capacity (measured with Ferric Reducing Ability of Plasma
[FRAP] assay) in their blood plasma. A significant increase in the glutathione
transferase (GST) and GPX activities, malondialdehyde content and total
antioxidant capacity (measured with 2,2'-azino-bis(3-ethylbenzothiazoline-6
sulphonic acid) [ABTS] assay) in the blood plasma of underfed goats compared with
controls was observed, while the opposite happened for the GR and SOD activities.
The underfeeding in both animal species caused a significant increase in the
protein carbonyls (PC) content of their blood plasma. The overfeeding, compared
with the control, caused a significant decline in the GPX activity and total
antioxidant capacity (measured with FRAP) in the blood plasma of sheep while the
opposite happened for the GPX and GST activities in the case of goats. The
overfed animals, of both species, compared with the respective controls, had
higher PC content in their blood plasma. The feeding level had no noticeable
impact on the antioxidants' enzymes activities of milk in both animal species.
Moreover, the underfeeding in the blood plasma and the overfeeding in milk of
both animal species resulted into a significant increase in the PC content.
Finally, only in sheep milk, the underfeeding, compared with the respective
control, and overfeeding reduced significantly the total antioxidant capacity
(measured with ABTS). The feeding level caused oxidative stress in both organism
and milk but the response was different in animal species and needs further
investigation.
PMID- 28508580
TI - 37 year snacking trends for US children 1977-2014.
AB - BACKGROUND: Previous studies have indicated that snacking is contributing to
increased calorie intake of American children and that the energy density of
snacks in US diets has increased in recent decades. OBJECTIVE: Examine short-term
and long-term trends in the energy density and food sources of snacks for US
children from 1977 to 2014, and examine whether trends differ between socio
demographic groups. METHODS: We used data collected from eight nationally
representative surveys of food intake in 49,952 US children age 2-18 years,
between 1977 and 2014. Overall patterns of snacking, trends in energy intake from
snacking, trends in food and beverage sources and energy density of snacks across
race-ethnic, age, gender, education and income groups were examined. RESULTS: In
all socio-demographic groups, there was a significant increase in per capita
energy intake deriving from snacks from 1977 to 2014 (P < 0.01). Salty snack
intake doubled over the study period, and sugar-sweetened beverage intake
decreased overall from 1977 to 2014 but increased in Non-Hispanic Blacks. Non
Hispanic Blacks had the largest increase in per capita intake from foods as a
snack from 1977 to 2014. Children in the lowest poverty level and household
education groups had more than 100% increase in calorie intake from snacks from
1977 to 2014. CONCLUSIONS: We found that snacking behaviour in the USA differs
between race-ethnic, household education, gender and income groups, yet snacking
remains a significant component of children's diets and the foods consumed at
these snacks are not the types of foods recommended by the US dietary guidelines.
PMID- 28508584
TI - Human intestinal spirochetosis in Japanese patients aged less than 20 years:
Histological analysis of colorectal biopsy and surgical specimens obtained from
479 patients.
AB - Human intestinal spirochetosis (HIS) is a condition in which spirochetes attach
to and colonize the colorectal epithelium. To our knowledge, no comprehensive
studies of HIS in young patient have been published in a developed country. This
study aimed to determine the incidence and clinicopathological manifestations of
HIS in Japanese patients aged less than 20 years. We retrospectively reviewed
3605 biopsy and 92 surgical specimens obtained from 479 patients admitted to
Shinshu University Hospital between 1997 and 2014. All slides were reviewed
independently by two pathologists to confirm the histological presence of
spirochetes. Among 387 patients who underwent biopsy, the most common pathologic
diagnosis was ulcerative colitis (12.6%, n = 49). Additionally, about half of the
biopsy specimens showed non-specific, mildly inflamed mucosa (50.6%, n = 196);
only one of these cases was HIS. On the other hand, among the surgical specimens,
we found no cases of HIS. We concluded that the incidence of HIS in Japanese
young patients was 0.2% (1/479 cases). The incidence of HIS in Japanese young
patients was very low, and one HIS case was associated with colitis with
abdominal pain.
PMID- 28508585
TI - Exploring the Molecular Growth of Two Gigantic Half-Closed Polyoxometalate
Clusters {Mo180 } and {Mo130 Ce6 }.
AB - Understanding the process of the self-assembly of gigantic polyoxometalates and
their subsequent molecular growth, by the addition of capping moieties onto the
oxo-frameworks, is critical for the development of the designed assembly of
complex high-nuclearity cluster species, yet such processes remain far from being
understood. Herein we describe the molecular growth from {Mo150 } and {Mo120 Ce6
} to afford two half-closed gigantic molybdenum blue clusters {Mo180 } (1) and
{Mo130 Ce6 } (2), respectively. Compound 1 features a hat-shaped structure with
the parent wheel-shaped {Mo150 } being capped by a {Mo30 } unit on one side.
Similarly, 2 exhibits an elliptical lanthanide-doped wheel {Mo120 Ce6 } that is
sealed by a {Mo10 } unit on one side. Moreover, the observation of the parent
uncapped {Mo150 } and {Mo120 Ce6 } clusters as minor products during the
synthesis of 1 and 2 strongly suggests that the molecular growth process can be
initialized from {Mo150 } and {Mo120 Ce6 } in solution, respectively.
PMID- 28508587
TI - Organic-Inorganic Hybrid Perovskite with Controlled Dopant Modification and
Application in Photovoltaic Device.
AB - Organic-inorganic hybrid perovskite as a kind of promising photovoltaic material
is booming due to its low-cost, high defect tolerance, and easy fabrication,
which result in the huge potential in industrial production. In the pursuit of
high efficiency photovoltaic devices, high-quality absorbing layer is essential.
Therefore, developing organic-inorganic hybrid perovskite thin films with good
coverage, improved uniformity, and crystalline in a single pass deposition is of
great concern in realizing good performance of perovskite thin-film solar cell.
Here, it is found that the introduction of suitable amounts of LiI plays a
dramatically positive role in enlarging the grain size and reducing the grain
boundaries of absorbing layer. In addition, the carrier lifetime and built-in
potential of the LiI doped perovskite device are observed to increase. Thus, it
leads to about 15% gain in solar cell efficiency comparing to that without the
LiI doping. Meanwhile, a hysteresis reduction is observed and 18.16% power
conversion efficiency is achieved in LiI doped perovskite device, as well.
PMID- 28508586
TI - Role and regulation of autophagy and apoptosis by nitric oxide in hepatic
stellate cells during acute liver failure.
AB - BACKGROUND & AIMS: We previously found that hepatic stellate cell activation
induced by autophagy maintains the liver architecture to prevent collapse during
acute liver failure. Nitric oxide has shown to induce hepatic stellate cell
apoptosis. Whether and how nitric oxide is involved in acute liver failure and
autophagy remains unclear. METHODS: Acute liver failure patients were recruited
to investigate the correlation between plasma nitric oxide levels and clinical
features. Liver tissues were collected from chronic hepatitis patients by biopsy
and from acute liver failure patients who had undergone liver transplantation.
The expression of nitric oxide synthases and hepatic stellate cell activation
(alpha-SMA), and autophagic activity (LC3) were investigated by
immunohistochemistry. Autophagy and apoptosis were investigated by immunoblot
analysis, confocal microscopy, and flow cytometry in hepatic stellate cells
treated with nitric oxide donors. RESULTS: Plasma nitric oxide level was
significantly increased in patients with acute liver failure compared to those
with cirrhosis (53.60+/-19.74 MUM vs 19.40+/-9.03 MUM, Z=-7.384, P<.001) and
positively correlated with MELD-Na score (r=.539, P<.001), implicating nitric
oxide in acute liver failure. At least some Nitric oxide was produced by
overexpression of inducible nitric oxide synthases and endothelial nitric oxide
synthases, but not neuronal nitric oxide synthases in the liver tissue. In vivo
observation revealed that autophagy was inhibited in hepatic stellate cells based
on decreased LC3 immunostaining, and in vitro experiments demonstrated that
Nitric oxide can inhibit autophagy. Moreover, nitric oxide promoted hepatic
stellate cell apoptosis, which was rescued by an autophagy inducer. CONCLUSIONS:
Increased nitric oxide synthases/ nitric oxide promotes apoptosis through
autophagy inhibition in hepatic stellate cells during acute liver failure,
providing a novel strategy for the treatment of patients with acute liver
failure.
PMID- 28508588
TI - At the Cross Section of Thrombotic Microangiopathy and Atypical Hemolytic Uremic
Syndrome: A Narrative Review of Differential Diagnostics and a Problematization
of Nomenclature.
AB - Complement-mediated atypical hemolytic uremic syndrome (aHUS) is a rare disease
associated with high mortality and morbidity. Renal biopsies often indicate
thrombotic microangiopathy (TMA). The condition is caused by an excessive
activation of the alternative pathway leading to depositions of membrane attack
complexes (MAC) on host cells. It may depend on mutations in complement
components and regulatory proteins, or the formation of complement-specific
antibodies. Mainly, an environmental trigger (e.g. infection) is needed for the
excessive response to develop. The clinical characteristics are more or less
shared with a wide range of diseases manifesting with microangiopathic hemolytic
anemia. Because of prior deficits in pathogenic understanding, associated
nomenclature has been based on clinical symptoms. New knowledge challenges these
symptomatic definitions; however, an outdated terminology is still being applied
in clinical practice to various extents. With respect to gained insights, it is
more advantageous to rebuild the concepts on etiological and pathogenic grounds.
The need for more distinct definitions is even more urgent in the light of the
effective treatment regimen with eculizumab for complement-mediated aHUS. This
review presents an up-to-date summary of the field of investigation, addresses
the need for faster differential diagnostics and proposes a revised nomenclature
based on the current pathogenic understanding.
PMID- 28508590
TI - Absenteeism in Head Start and Children's Academic Learning.
AB - Using nationally representative data from the Family and Child Experiences Survey
2009 cohort (n = 2,842), this study examined the implications of 3- and 4-year
old's absences from Head Start for their early academic learning. The findings
from this study revealed that children who missed more days of school, and
especially those who were chronically absent, demonstrated fewer gains in areas
of math and literacy during the preschool year. Moreover, excessive absenteeism
was found to detract from the potential benefits of quality preschool education
and was especially problematic for the early learning of children who entered the
Head Start program with a less developed skill set. Implications for policy and
practice are discussed.
PMID- 28508589
TI - Identification of a novel HLA allele, HLA-B*41:50, in a French individual.
AB - The novel HLA-B*41:50 allele differs from HLA-B*41:01:01 by a single nucleotide
substitution at codon 116.
PMID- 28508591
TI - Serious Offenders: Using Evidence to Predict and Manage the Risk.
AB - In response to the risk of serious further offences, an evidence-based approach
is needed in risk management. A recent joint prison-probation inspection of the
management of life sentence prisoners in six U.K. prisons found that the quality
of assessment and plans to manage risk of harm to others was insufficient, with
too much focus on the offender's verbal account. The present paper discusses
observations of regular prisoner behaviour as the basis for predictions, and
summarizes results of an evaluation of this methodology based on a sample of high
risk category prisoners released into the community. Prison behaviour has not
traditionally been seen as a valid risk marker for violent recidivism, which may
be because typically only conspicuous high-level behaviours are considered by
risk management panels. Our research suggests that we are neglecting a valuable
source of information on risk by failing to observe on-going and consistent pre
release behaviour. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28508592
TI - Confining Functional Nanoparticles into Colloidal Imine-Based COF Spheres by a
Sequential Encapsulation-Crystallization Method.
AB - Here, a two-step method is reported that enables imparting new functionalities to
covalent organic frameworks (COFs) by nanoparticle confinement. The direct
reaction between 1,3,5-tris(4-aminophenyl)benzene and 1,3,5
benzenetricarbaldehyde in the presence of a variety of metallic/metal-oxide
nanoparticles resulted in embedding of the nanoparticles in amorphous and non
porous imine-linked polymer organic spheres (NP@a-1). Post-treatment reactions of
NP@a-1 with acetic acid under reflux led to crystalline and porous imine-based
COF-hybrid spheres (NP@c-1). Interestingly, Au@c-1 and Pd@c-1 were found to be
catalytically active.
PMID- 28508594
TI - meso-Cumulenic 2H-Corroles from meso-Ethynyl-3H-corroles.
AB - Alkynyl-substituted 3H-corrole 9 a was converted to [3]cumulenic 2H-corrole 10 a
by treatment with trimethylsilyl chloride (TMSCl), and 1,3-butadiyne-bridged 3H
corrole dimer 11 b was transformed into [5]cumulene-bridged 2H-corrole dimer 12 b
by oxidation with PbO2 . Both 10 a and 12 b were metalated to form ZnII complexes
10 a-Zn and 12 b-Zn. The structures of 10 a-Zn and 12 b-Zn show planar
conformations with bond-length alternations that are analogous to those of
tetraaryl [n]cumulenes. The cumulenic corrole dimers 12 b and 12 b-Zn display
large NIR absorption bands in the range of 700-1400 nm (maximum epsilon~1.0*105
m-1 cm-1 ) owing to the effective pi-conjugation between the two corrole units
through the [5]cumulene bridge.
PMID- 28508593
TI - Missense variant pathogenicity predictors generalize well across a range of
function-specific prediction challenges.
AB - The steady advances in machine learning and accumulation of biomedical data have
contributed to the development of numerous computational models that assess the
impact of missense variants. Different methods, however, operationalize impact
differently. Two common tasks in this context are the prediction of the
pathogenicity of variants and the prediction of their effects on a protein's
function. These are related but distinct problems, and it is unclear whether
methods developed for one are optimized for the other. The Critical Assessment of
Genome Interpretation (CAGI) experiment provides a means to address this question
empirically. To this end, we participated in various protein-specific challenges
in CAGI with two objectives in mind. First, to compare the performance of methods
in the MutPred family with the state-of-the-art. Second and more importantly, to
investigate the applicability of general-purpose pathogenicity predictors to the
classification of specific function-altering variants without additional training
or calibration. We find that our pathogenicity predictors performed competitively
with other methods, outputting score distributions in agreement with experimental
outcomes. Overall, we conclude that binary classifiers learned from disease
causing mutations are capable of modeling important aspects of the underlying
biology and the alteration of protein function resulting from mutations.
PMID- 28508596
TI - In Memoriam: Juan Jorge Heinrich, MD, PhD (1937-2016).
PMID- 28508595
TI - Silver nanoparticle deposited implants to treat osteomyelitis.
AB - In this study, electrolytically deposited strongly adherent silver nanoparticles
on stainless-steel (SS) implants were used for in situ osteomyelitis treatment.
Samples were heat treated to enhance adhesion of silver on 316 L SS. Ex vivo
studies were performed to measure silver-release profiles from the 316 L SS
screws inserted in equine cadaver bones. No change in the release profiles of
silver ions were observed in vitro between the implanted screws and the control.
In vivo studies were performed using osteomyelitic rabbit model with 3 mm
diameter silver-deposited 316 L SS pins at two different doses of silver: high
and low. Infection control ability of the pins for treating osteomyelitis in a
rabbit model was measured using bacteriologic, radiographic, histological, and
scanning electron microscopic studies. Silver-coated pins, especially high dose,
offered a promising result to treat infection in animal osteomyelitis model
without any toxicity to major organs. (c) 2017 Wiley Periodicals, Inc. J Biomed
Mater Res Part B: Appl Biomater, 106B: 1073-1083, 2018.
PMID- 28508597
TI - In Memoriam: Melvin M. Grumbach, MD, (1925-2016) Pediatric Endocrinologist,
Scientist, Educator, Leader.
PMID- 28508598
TI - For Debate: Should We Worry about Hematospermia in Adolescents and Young Men? A
Report of Six Cases and Review of the Literature.
AB - Hematospermia or hemospermia is defined as the presence of blood in ejaculate.
The true prevalence of the condition is unknown because many cases escape the
patient's notice, and remain unrecognized and unreported. There are two main aims
in the patient evaluation: first, to ensure that there is no specific condition
that is treatable; second, to reassure the patient's parents that no causative
factor is present. Many physicians are unfamiliar with this disorder and this
forms the basis for our current review. We performed an essentially English
language search (Medline since 1966 to present and reference list of articles)
for "hematospermia", or "hemospermia" in combination with "adolescents", "young
adults", "genital diseases", "management" and "review". The authors' personal
experience with 6 adolescents and young men (up to the age of 20 years) is also
reported. Several anatomical structures contributing to the ejaculate may be the
source of the hematospermia: seminal vesicles, prostate, testis and epididymis.
Hematospermia is a generally benign and self-limited condition that is
infrequently associated with significant underlying pathology. Once the diagnosis
is clear, it is important to reassure the adolescent about the benign nature and
self-limiting course of the condition and to provide appropriate treatment to
help ensure the adolescent's normal sexual development.
PMID- 28508599
TI - IMAGe and Related Undergrowth Syndromes: The Complex Spectrum of Gain-of-Function
CDKN1C Mutations.
AB - CDKN1C is a cyclin-dependent kinase Inhibitor and negative regulator of cellular
proliferation. Recently, gain-of-function mutations in the PCNA domain of CDKN1C
have been reported as the genetic basis of various growth-retarded syndromes
including IMAGe syndrome, Russell Silver syndrome as well as a novel undergrowth
syndrome that additionally exhibited early adulthood onset diabetes. This review
summarizes the key clinical features and the molecular advances that have
contributed to our understanding of this complex phenotypic spectrum.
PMID- 28508600
TI - Endocrine Disorders Developing after Surgical Intervention of Craniopharyngioma
in Children.
AB - Craniopharyngiomas, albeit their benign nature, can cause severe damage to
visual, hypothalamic, endocrine and neurologic functions which make their total
resection an inevitable approach to save the patient's life. However, significant
therapy-related long term complications make those traditional treatment options
debatable and hazardous. This review will focus on the various complications that
affect the childrens' quality of life considerably such as, diabetes insipidus,
precocious puberty and hypothalamic obesity.
PMID- 28508601
TI - Effects of Anorexia Nervosa on the Endocrine System.
AB - Anorexia nervosa (AN) is characterized by severe undernutrition associated with
alterations in multiple endocrine axes, which are primarily adaptive to the state
of caloric deprivation. Hormonal changes include growth hormone (GH) resistance
with low insulin like growth factor-1 (IGF-1) levels, hypothalamic hypogonadism,
relative hypercortisolemia and changes in appetite regulating hormones, including
leptin, ghrelin, and peptide YY. These alterations contribute to abnormalities in
bone metabolism leading to low bone mass, impaired bone microarchitecture, and
increased risk for fracture, and may also negatively impact cognition, emotions
and mood. The best strategy to improve all biologic outcomes is weight and
menstrual recovery. Physiological estrogen replacement improves bone accrual
rates and measures of trait anxiety in adolescents with AN. Other therapies
including testosterone and IGF-1 replacement, and use of DHEA with oral estrogen
progesterone combination pills, bisphosphonates and teriparatide have also been
studied to improve bone outcomes.
PMID- 28508602
TI - Succinate-Dehydrogenase Deficient Paragangliomas/Pheochromocytomas: Genetics,
Clinical Aspects and Mini- Review.
PMID- 28508603
TI - Meeting Reports: Adolescence - a Transition to Adulthood Proceedings of the 24th
Aschauer Soiree, held at Jurata, Poland, November 5th 2016.
PMID- 28508604
TI - For Debate: Growth Hormone Treatment of Infants Born Small for Gestational Age
should be Started at or before the First Year of Age.
AB - Children born small for gestational age without early catch-up of somatic growth
and head circumference subsequently remain short and suffer from various degrees
of neurocognitive and psychological impairment. Based upon the role of growth
hormone (GH) and insulin-like growth factor-I on early brain growth and
maturation, we propose that GH treatment of these infants be instituted prior to
their 2nd birthday.
PMID- 28508605
TI - Disorders of Adrenal Steroidogenesis: Impact on Gonadal Function and Sex
Development.
AB - A defect in adrenal steroidogenesis may cause a disorder of sex development
(DSD). Importantly, DSD of adrenal origin is not restricted to a genital
phenotype but is in most cases accompanied by mild to severe impairment in
glucocorticoid and/or mineralocorticoid synthesis. If a patient is suspected of
DSD of adrenal origin evaluation of glucocorticoid and mineralocorticoid
metabolism is therefore essential to provide adequate medical care in the case of
a severe and potentially life-threatening insufficiency. The adrenal
steroidogenic defects causing DSD, their clinical features and diagnostic work-up
are discussed. In this review we provide an overview of defects in the adrenal
steroidogenesis and its impact on gonadal function and sex development.
PMID- 28508607
TI - Sequelae of GH Treatment in Children with PWS.
AB - More than 15 years after rGH was granted marketing authorization for children
with PWS, a review of the sequelae, side effects and safety issues of rGH therapy
is timely. The publications on issues concerning respiratory function, glucose
metabolism, fat mass, and scoliosis at baseline and with rGH treatment are herein
presented. We discuss the impact of rGH side effects, make proposals to prevent
or treat them, and emphasise the remaining questions and perspectives. As a
whole, the benefit /risk ratio is positive, although questions are raised about
the role of GH in premature pubarche and its long-term effects, particularly the
potential long-term oncogenic risk. The organisation of care in dedicated or
reference centres at the national and European level will facilitate the
collection and analysis of data and serve as a paradigm for long-term follow-up.
PMID- 28508606
TI - Surgery in Focal Congenital Hyperinsulinism (CHI) - The "Hyperinsulinism Germany
International" Experience in 30 Children.
AB - OBJECTIVES: Results of surgery for focal CHI in 30 children PATIENTS AND METHODS:
All showed an ABCC8 or KCNJ11 mutation. After PET/CT in 29 children and PET/MRT
in 1 case, frozen-section guided resection was performed, in left-sided cases by
laparoscopy. Mean age at surgery was 11.7 months (2-49). RESULTS: In 28/30
children, the PET/CT or MRT correlated with histopathology. In two cases, a focal
lesion was undectable; one of these was cured, one not. In total, 24 children
showed lesions with sizes of 5-12 mm. All were cured instantly. In four children
with huge lesions in the pancreatic head, pathological cells remained at the
resection margins. One child was cured instantly, two children after a 2nd
surgery, and one child was not cured, even after three surgeries. The overall
cure rate was 93%. CONCLUSIONS: Imaging, surgical findings, histopathology and
clinical outcome in surgery for focal CHI match in most, but not all cases.
PMID- 28508608
TI - Myopathy in Pediatric Thyroid States: A Review of the Literature.
AB - This review highlights the presentations of myopathy in children in both
hypothyroid and hyperthyroid states with an emphasis on the pathophysiology,
diagnosis and treatment. Based on our review of the literature data, myopathy
should be considered in all children presenting with muscular weakness or altered
muscle enzymes in the context of thyroid disease.
PMID- 28508609
TI - Oral Health in Children with Obesity or Diabetes Mellitus.
AB - Oral health status must be considered in the care of children with obesity (OB)
and diabetes mellitus (DM). The health of these patients' mouths may have
significant effects on their overall health and evolution of their disease. Here
we address periodontal disease (PD) and dental caries (DC), since these are two
of the most common chronic diseases affecting OB and DM patients. OB plays a
plausible role in the development of PD. Both overall OB and central adiposity
are associated with increased hazards of gingivitis and its progression to PD.
The inflammatory changes of PD might not be limited to the oral cavity, these may
also trigger systemic consequences. Patients with type 1 and type 2 diabetes
mellitus (T1DM, T2DM) present an increased prevalence of gingivitis and PD. In
diabetics PD develops at a younger age than in the healthy population, it also
worsens with the prolongation of DM. The progression to PD has been correlated
with the metabolic control of the disease as it is more prevalent and more severe
in patients with elevated hemoglobin A1c (A1c) levels. PD negatively affects
glycemic control and other diabetes related complications and there is a general
consensus that treatment of PD can positively influence these negative effects.
Additionally, DC is a multifactorial oral disease that is frequently detected in
those with OB and DM, although its prevalence in systematic reviews is
inconclusive. The associations between gingivitis, PD and DC share similar
behaviors, i.e. inadequate oral hygiene habits and unhealthy dietary intake.
Insufficient tooth brushing and intake of sugary foods may result in greater
detrimental oral effects. Maintaining oral health will prevent oral chronic
diseases and ameliorate the consequences of chronic inflammatory processes. Thus,
the care of obese and diabetic patients requires a multidisciplinary team with
medical and dental health professionals.
PMID- 28508610
TI - Meeting Reports: 2016 Annual Meeting of the Pediatric Endocrine Society
Baltimore, MD (April 29-May 2, 2016) Selected Highlights.
PMID- 28508611
TI - Worth Remembering: Eugenio Muller, MD, 1933-2015.
PMID- 28508612
TI - The Longevity Hormone Klotho is a New Player in the Interacion of the Growth
Hormone/Insulin-Like Growth Factor 1 Axis.
AB - Klotho was first discovered as an aging-suppressor gene. Mice that do not express
klotho die prematurely with multiple symptoms of aging, several of which are also
characteristic of decreased GH/IGF-1 axis activity. Klotho is highly expressed in
the brain, the kidney, and parathyroid and pituitary glands, but can also serve
as a circulating hormone by its shedding, forming soluble klotho (sKlotho) that
can be detected in blood, cerebrospinal fluid and urine. Several lines of
evidence suggest an association between klotho levels and activity of the GH/IHG
1 axis: The GH-secreting cells in the anterior pituitary of klotho-deficient mice
are hypotrophic; klotho levels are altered in subjects with pathologies of the
GH/IGF-1 axis; and accumulating data indicate that klotho is a direct regulator
of GH secretion. Thus, klotho seems to be a new player in the intricate
regulation of the GH/IGF-1 axis.
PMID- 28508613
TI - Genetic Mutations, Birth Lengths, Weights and Head Circumferences of Children
with IGF-I Receptor Defects. Comparison with other Congenital Defects in the
GH/IGF-I axis.
AB - BACKGROUND: In recent years more and more genetic defects along the GHRH-GH-IGF-I
axis have been reported. Mutations of the IGF-I receptor (R) are a rare
abnormality of whom only the heterozygote progenies survive. OBJECTIVES: To
summarize, from the literature, data on birth length, weight and head
circumference of neonates with IGF-I-R mutations, and to correlate the data with
that of other types of mutations in the GH/IGF-I axis. SUBJECTS: Sixty seven
neonates from 24 published articles were included and forty seven different
mutations of the IGF-I (R) located on chromosome 15 have been identified.
RESULTS: Mean (+/-SD) birth length (BL), available for 26, (10 M, 16F) neonates
with a gestational age of 34-41weeks, was 44.2+/-4cm; one was premature (30cm at
31 weeks). There was a significant correlation between birth length and
gestational age (GA) r=0.71 (p>.001). Mean birth weight (BW) of 41 neonates (18M,
23F) was 2388+/-743gr. Two premature neonates weighed 650gr and 950gr
respectively. The BW correlated significantly with gestational age, (males:
r=0.68; p=0.007, females: r=0.49; p=0.024). The BMI of 25 neonates ranged from 6
to 13. In 22 records marked microcephaly was ascertained or stated. Nine of 16
mothers were short (133 -148cm), m+/-SD = 150.5+/-7.3cm.
PMID- 28508614
TI - Methods for Rating Sexual Development in Girls.
AB - Sexual maturity rating (SMR) is important in population studies and in clinical
care. Pubertal staging allows doctors to assess the maturation of adolescents to
correlate several pubertal phenomena such as age at menarche, growth spurt and
final height, to advise and manage patients appropriately and to have sensitive
"sensors" of the effects of environmental exposure on human populations. The
commonly used markers of the timing of female puberty are thelarche and menarche.
Appearance of the breast bud is the first indicator of puberty onset in 90% of
girls. Assessment of thelarche may be performed by a physician with expertise in
adolescents or by self-assessment, in which the adolescent identifies her stage
of maturation based on Tanner's photographs/illustrations. The assessment of
Tanner stages by professionals provides more reliable information than self
assessment but may involve variations between observers. Tanner self-assessment
has been proposed as an alternative in various studies. Some studies have found
reasonable agreement between self-assessment and examination by a physician
whereas others found discrepancies. Measuring nipple and areola diameters is
feasible for sexual maturation staging. Both sizes show a significant increase
during pubertal development and after menarche. However, the ratings using
nipple/areola method need to be analyzed to establish their degree of concordance
with standard techniques and other markers of development in girls.
PMID- 28508615
TI - A Multidisciplinary Approach to Puberty and Fertility in Girls with Turner
Syndrome.
AB - Women with Turner Syndrome (TS) have a variety of medical needs throughout their
lives; however, the peripubertal years are particularly challenging. From a
medical perspective, the burden of care increases during this time due to growth
optimization strategies, frequent health screenings, and puberty induction.
Psychologically, girls begin to comprehend the long-term implications of the
condition, including their diminished fertility potential. Unfortunately, clear
guidelines for how to best approach this stage have not been established. It
remains to be determined what is the best age to begin treatment; the best
compound, dose, or protocol to induce puberty; how, when or what to discuss
regarding fertility and potential fertility preservation options; and how to
support them to accept their differences and empower them to take an active role
in their care. Given the complexity of this life stage, a multidisciplinary
treatment team that includes experts in endocrinology, gynecology, and psychology
is optimal.
PMID- 28508617
TI - Letters to the Editor: Response to "Thyroid Hemiagenesis from Childhood to
Adulthood: Review of Literature and Personal Experience" by Vincenzo De Sanctis,
MD, Ashraf T Soliman, MD, PhD, FRCP, Salvatore Di Maio, MD, Heba Elsedfy, MD,
Nada A Soliman, MD, Rania Elalaily, MD.
PMID- 28508616
TI - Ultrasound Elastography in Pediatric Congenital Hypothyroid Patients.
AB - OBJECTIVES: Congenital hypothyroidism (CH) is most frequently encountered in
newborns as an endocrine disorder characterized by thyroid hormone deficiency,
and is one of the most common reasons for preventable mental retardation. This
prospective study was designed to detect the pediatric occurrences of CH followed
as euthyroid, with no anomalies detected via US on the gray scale, in comparison
with a pediatric group with normal levels. METHODS: A total of 42 apparently
healthy children with no thyroid disorder (Group 1) and 54 euthyroid CH (Group 2)
using thyroid hormone were included in this study. Both B-mode gray scale
ultrasound (US) and elastography examinations were made using Toshiba Aplio 400
device (Toshiba Medical Systems Corporation, Otawara, Japan), with a 12 MHz
linear probe. All the radiological examinations were made by a single radiologic
physician with at least 5 years of experience in elastography. RESULTS: In total,
96 occurrences in the right and left lobes of 192 thyroid gland measurements were
included in the research. There were 20 males and 22 females in the healthy group
(n=42), and 28 males and 26 females in the CH group (n=54). Although, there were
no significant differences in the average age or gender (p=0.563), there were
significant differences in the strain index (SI) values in the CH group.The
receiver operating characteristics (ROC) curve was done to calculate the cut-off
value for diagnosing CH with strain index ratio (SIR); the value of the cut-off
was 0.695, with 63.1% sensitivity and 50.9% specificity. CONCLUSIONS: This was
the first study about CH in children. Our study found the SIR of CH to be higher
than the normal thyroid parenchyma. It showed that in parenchymal related CH, SE
should be used. This study should be a guide for new studies that should be done
about the different etiological factors of CH.
PMID- 28508618
TI - Meeting Report: Festive Symposium Honoring Lynne L. Levitsky, MD, Boston April
4th, 2016.
PMID- 28508619
TI - Meeting Report: 2016 Annual Meeting of the Endocrine Society Boston, MA (April 1
4, 2016) Selected Highlights.
PMID- 28508621
TI - Extending the Use of Diffusive Gradients in Thin Films (DGT) to Solutions Where
Competition, Saturation, and Kinetic Effects Are Not Negligible.
AB - DGT (Diffusion Gradients in Thin films) was designed to sample trace metals in
situ at their natural concentrations. The setup and the experimental deployment
conditions were established to allow interpretation of a linear accumulation of
metal with time, using a simple expression based on a steady-state flux under
perfect sink conditions. However, the extension of DGT to a wide range of
analytes and its use under varied conditions has shown that, in some situations,
these conditions are not fulfilled, so that accumulations with time are
nonlinear. Previously, when such curvature was observed, concentrations in
solution could not be reliably calculated. Here, we present fundamentally derived
equations that reproduce the time accumulation for three situations: (i) kinetic
limitations in the binding to the resin, (ii) saturation or equilibrium effects,
or (iii) non-negligible competitive effects. We show how the accumulations can be
quantified, in terms of the required kinetic and thermodynamic constants, and
provide practical guidance for their use to obtain reliable estimates of solution
concentrations. Solutions containing Mg or Mn, where all three situations can
prevail, are used as examples. Calculated concentrations show reasonable
agreement with the experimentally known values and with the results of a
numerical model of the system, significantly improving the estimations based on
perfect sink conditions. Such an approach opens up the possibility of using DGT
more widely in challenging systems and allows DGT data to be interpreted more
fully.
PMID- 28508620
TI - [Prevalence of human papillomavirus in Spanish women from a population screening
program].
AB - OBJECTIVE: The human papillomavirus (HPV), is necessary to cause a woman
developing cervical cancer. The aim of the study was to estimate the prevalence
of women with HPV infection, covered by the program of prevention and early
detection of cervical cancer of Castile and Leon (Spain). METHODS: Samples of
women included in the screening program were analyzed. Including a total of
120,326 cervical swab samples, collected in the period from January 2012 to
December 2014. RESULTS: 12,183 HPV positive samples were detected, representing a
prevalence of 9.6 0/00, (IC 95% 9.5%-9.8%) in the female population. High-risk
HPV were found in higher proportion that HPV low-risk genotypes. HPV prevalence
correlates inversely with women age. Coinfections of multiple genotypes were
found in one third of screened women population. CONCLUSIONS: Data showed in this
study are the first and wider Spanish results from a cervical cancer screening
program population non opportunistic based on HPV detection. These results would
serve as a reference for future prevalence studies and to evaluate the future
impact of HPV vaccination campaigns.
PMID- 28508622
TI - Correlation of Interface Impurities and Chemical Gradients with High
Magnetoelectric Coupling Strength in Multiferroic BiFeO3-BaTiO3 Superlattices.
AB - The detailed understanding of magnetoelectric (ME) coupling in multiferroic oxide
heterostructures is still a challenge. In particular, very little is known to
date concerning the impact of the chemical interface structure and unwanted
impurities that may be buried within short-period multiferroic BiFeO3-BaTiO3
superlattices during growth. Here, we demonstrate how trace impurities and
elemental concentration gradients contribute to high ME voltage coefficients in
thin-film superlattices, which are built from 15 double layers of BiFeO3-BaTiO3.
Surprisingly, the highest ME voltage coefficient of 55 V cm-1 Oe-1 at 300 K was
measured for a superlattice with a few atomic percent of Ba and Ti that diffused
into the nominally 5 nm thin BiFeO3 layers, according to analytical transmission
electron microscopy. In addition, highly sensitive enhancements of the cation
signals were observed in depth profiles by secondary ion mass spectrometry at the
interfaces of BaTiO3 and BiFeO3. As these interface features correlate with the
ME performance of the samples, they point to the importance of charge effects at
the interfaces, that is, to a possible charge mediation of ME coupling in oxide
superlattices. The challenge is to provide cleaner materials and processes, as
well as a well-defined control of the chemical interface structure, to push
forward the application of oxide superlattices in multiferroic ME devices.
PMID- 28508623
TI - Integrating Nature, People, and Technology To Tackle the Global Agri-Food
Challenge.
PMID- 28508624
TI - Temperature Treatment of Highly Porous Zirconium-Containing Metal-Organic
Frameworks Extends Drug Delivery Release.
AB - Utilizing metal-organic frameworks (MOFs) as a biological carrier can lower the
amount of the active pharmaceutical ingredient (API) required in cancer
treatments to provide a more efficacious therapy. In this work, we have developed
a temperature treatment process for delaying the release of a model drug compound
from the pores of NU-1000 and NU-901, while taking care to utilize these MOFs'
large pore volume and size to achieve exceptional model drug loading percentages
over 35 wt %. Video-rate super-resolution microscopy reveals movement of MOF
particles when located outside of the cell boundary, and their subsequent
immobilization when taken up by the cell. Through the use of optical sectioning
structured illumination microscopy (SIM), we have captured high-resolution 3D
images showing MOF uptake by HeLa cells over a 24 h period. We found that
addition of a model drug compound into the MOF and the subsequent temperature
treatment process does not affect the rate of MOF uptake by the cell. Endocytosis
analysis revealed that MOFs are internalized by active transport and that
inhibiting the caveolae-mediated pathway significantly reduced cellular uptake of
MOFs. Encapsulation of an anticancer therapeutic, alpha-cyano-4-hydroxycinnamic
acid (alpha-CHC), and subsequent temperature treatment produced loadings of up to
81 wt % and demonstrated efficacy at killing cells beyond the burst release
effect.
PMID- 28508625
TI - High-Performance Red-Light Photodetector Based on Lead-Free Bismuth Halide
Perovskite Film.
AB - In this study, we developed a sensitive red-light photodetector (RLPD) based on
CsBi3I10 perovskite thin film. This inorganic, lead-free perovskite was
fabricated by a simple spin-coating method. Device analysis reveals that the as
assembled RLPD was very sensitive to 650 nm light, with an on/off ratio as high
as 105. The responsivity and specific detectivity of the device were estimated to
be 21.8 A/W and 1.93 * 1013 Jones, respectively, which are much better than those
of other lead halide perovskite devices. In addition, the device shows a fast
response (rise time: 0.33 ms; fall time: 0.38 ms) and a high external quantum
efficiency (4.13 * 103%). It is also revealed that the RLPD has a very good
device stability even after storage for 3 months under ambient conditions. In
summary, we suggest that the CsBi3I10 perovskite photodetector developed in this
study may have potential applications in future optoelectronic systems.
PMID- 28508626
TI - Red Emissive Sulfur, Nitrogen Codoped Carbon Dots and Their Application in Ion
Detection and Theraonostics.
AB - It is highly desirable and a great challenge for red light emission of carbon
dots under long wavelength excitation. Here, we developed a facile route to
synthesize carbon dots with red emission due to the doping effect of S and N
elements, borrowing from the concept of the semiconductor. The maximum emission
locates at 594 nm under 560 nm excitation. The absolute photoluminescence (PL)
quantum yield (QY) is as high as 29% and 22% in ethanol and water, respectively.
XPS and FTIR spectra illustrated that there exist -SCN and -COOH groups on the
surface of the carbon dots. They endow the carbon dots with high sensitivity for
ion detection of Fe3+. The quenched PL emission of Fe3+-S,N-CDs can be recovered
by adding ascorbic acid to release the -COOH and -SCN group due to Fe2+ formation
in the presence of ascorbic acid. High PL QY of red emission is beneficial to
application in bioimaging. Doxorubicin was loaded onto carbon dots through pi-pi
stacking to form a theranostic agent. When the CD-Dox was injected into the tumor
site, a strong PL emission was observed. The PL intensity indicates the
concentration of the theranostic agent. After 7 times injection, both the tumor
size and weight clearly decrease. The results demonstrate that the S,N-CDs are a
potentially excellent bioimaging component in the theranostic field.
PMID- 28508627
TI - Fabrication of Ag-Cu2O/Reduced Graphene Oxide Nanocomposites as Surface-Enhanced
Raman Scattering Substrates for in Situ Monitoring of Peroxidase-Like Catalytic
Reaction and Biosensing.
AB - Highly sensitive biosensors are essential in medical diagnostics, especially for
monitoring the state of an individual's disease. An ideal way to achieve this
objective is to analyze human sweat secretions by noninvasive monitoring. Due to
low concentrations of target analytes in human secretions, fabrication of
ultrasensitive detection devices is a great challenge. In this work, Ag
Cu2O/reduced graphene oxide (rGO) nanocomposites were prepared by a facile two
step in situ reduction procedure at room temperature. Ag-Cu2O/rGO nanocomposites
possess intrinsic peroxidase-like activity and rapidly catalyze oxidation of the
peroxidase substrate 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of
H2O2. On the basis of the excellent SERS properties and high peroxidase-like
activity of the Ag-Cu2O/rGO nanocomposites, the catalytic oxidation of TMB can be
monitored by SERS. This approach can detect H2O2 and glucose with high
sensitivity and distinguish between diabetic and normal individuals using glucose
levels in fingerprints. Our work provides direction for designing other SERS
substrates with high catalytic activity and the potential for application in
biosensing, forensic investigation, and medical diagnostics.
PMID- 28508628
TI - Defect Dominated Charge Transport and Fermi Level Pinning in MoS2/Metal Contacts.
AB - Understanding the electronic contact between molybdenum disulfide (MoS2) and
metal electrodes is vital for the realization of future MoS2-based electronic
devices. Natural MoS2 has the drawback of a high density of both metal and sulfur
defects and impurities. We present evidence that subsurface metal-like defects
with a density of ~1011 cm-2 induce negative ionization of the outermost S atom
complex. We investigate with high-spatial-resolution surface characterization
techniques the effect of these defects on the local conductance of MoS2. Using
metal nanocontacts (contact area < 6 nm2), we find that subsurface metal-like
defects (and not S-vacancies) drastically decrease the metal/MoS2 Schottky
barrier height as compared to that in the pristine regions. The magnitude of this
decrease depends on the contact metal. The decrease of the Schottky barrier
height is attributed to strong Fermi level pinning at the defects. Indeed, this
is demonstrated in the measured pinning factor, which is equal to ~0.1 at defect
locations and ~0.3 at pristine regions. Our findings are in good agreement with
the theoretically predicted values. These defects provide low-resistance
conduction paths in MoS2-based nanodevices and will play a prominent role as the
device junction contact area decreases in size.
PMID- 28508630
TI - On-Surface Heck Reaction of Aryl Bromides with Alkene on Au(111) with Palladium
as Catalyst.
AB - The on-surface Heck reaction of aryl bromides with terminal alkene has been
achieved for the first time. With palladium as the catalyst, cross-coupling of
porphyrin-derived aryl bromides with terminal alkene proceeds with high
selectivity on an Au(111) surface, as determined by scanning tunneling microscopy
at the single molecular level. Density functional theory calculations suggest
that the on-surface Heck reaction proceeds via debromination of aryl bromide,
addition to the C?C bond, and elimination of hydrogen, ultimately affording the
cross-coupling product.
PMID- 28508629
TI - Inorganic Ligand Thiosulfate-Capped Quantum Dots for Efficient Quantum Dot
Sensitized Solar Cells.
AB - The insulating nature of organic ligands containing long hydrocarbon tails brings
forward serious limitations for presynthesized quantum dots (QDs) in photovoltaic
applications. Replacing the initial organic hydrocarbon chain ligands with
simple, cheap, and small inorganic ligands is regarded as an efficient strategy
for improving the performance of the resulting photovoltaic devices. Herein,
thiosulfate (S2O32-), and sulfide (S2-) were employed as ligand-exchange reagents
to get access to the inorganic ligand S2O32-- and S2--capped CdSe QDs. The
obtained inorganic ligand-capped QDs, together with the initial oleylamine-capped
QDs, were used as light-absorbing materials in the construction of quantum dot
sensitized solar cells (QDSCs). Photovoltaic results indicate that thiosulfate
capped QDs give excellent power conversion efficiency (PCE) of 6.11% under the
illumination of full one sun, which is remarkably higher than those of sulfide-
(3.36%) and OAm-capped QDs (0.84%) and is comparable to the state-of-the-art
value based on mercaptocarboxylic acid capped QDs. Photoluminescence (PL) decay
characterization demonstrates that thiosulfate-based QDSCs have a much-faster
electron injection rate from QD to TiO2 substrate in comparison with those of
sulfide- and OAm-based QDSCs. Electrochemical impedance spectroscopy (EIS)
results indicate that higher charge-recombination resistance between potoanode
and eletrolyte interfaces were observed in the thiosulfate-based cells. To the
best of our knowledge, this is the first application of thiosulfate-capped QDs in
the fabrication of efficient QDSCs. This will lend a new perspective to boosting
the performance of QDSCs furthermore.
PMID- 28508631
TI - Reductive Bis-addition of Aromatic Aldehydes to alpha,beta-Unsaturated Esters via
the Use of Sm/Cu(I) in Air: A Route to the Construction of Furofuran Lignans.
AB - The novel bis-addition of benzaldehydes to acrylates or maleates was achieved by
the direct use of samarium metal with the assistance of CuI under mild conditions
under dry air, and the useful 2-hydroxylalkyl-gamma-butyrolactons and lignan
derivatives were thus constructed with high efficiency. The key factors that
influence the reaction efficiency were investigated. The use of potassium iodide
and molecular sieves as additives can improve the reaction efficiency remarkably.
PMID- 28508632
TI - Colloidally Assembled Zinc Ferrite Magnetic Beads: Superparamagnetic Labels with
High Magnetic Moments for MR Sensors.
AB - Magnetic particles are widely used as labels in magnetoresistive sensors. To use
magnetic particles as labels, several important characteristics should be
considered, such as superparamagnetism, a high magnetic moment per particle (m),
facile surface functionalization and biomolecule immobilization, colloidal
stability, and analyte specificity. In this paper, we describe the preparation of
magnetic labels with a high m, using colloidal assemblies of superparamagnetic
zinc ferrite nanoparticles (ZFNPs, ~9 nm). Also, several properties of these
particles are compared with those of commercially available magnetic beads,
Dynabeads and TurboBeads. The colloidally assembled zinc ferrite magnetic beads
(ZFMBs, ~160 nm) were synthesized by assembling ZFNPs via an emulsion-based
assembly approach. While retaining superparamagnetism at room temperature, the m
of ZFMBs is ~4000* higher than that of the constituent ZFNPs. Surface
functionalization with a layer of polyacrylic acid stabilized the ZFMBs in
aqueous solution and enabled conjugation with streptavidin via carbodiimide
linking chemistry. The streptavidinated ZFMBs can be suspended in aqueous buffer
for >=24 h, whereas 1.05 MUm Dynabeads and 30 nm TurboBeads undergo ballistic
deposition and instantaneous aggregation in solution, respectively. Finally, the
streptavidinated ZFMBs were employed as labels in an immunoassay for the
detection of osteopontin, a potential pancreatic cancer marker, proving superior
to the commercial particles in terms of limit of detection and dynamic range. We
expect that the work presented in this article can be extended to other
biological applications, especially where superparamagnetic particles with a high
m and colloidal stability are needed.
PMID- 28508633
TI - Ionic Complexes of Metal Oxide Clusters for Versatile Self-Assemblies.
AB - The combination of rational design of building components and suitable
utilization of driving force affords spontaneous molecular assemblies with well
defined nanostructure and morphology over multiple length scales. The serious
challenges in constructing assemblies with structural advantages for the
realization of functions programmed into the building components usually lie
ahead since the process that occurs does not always follow the expected roadmap
in the absence of external intervention. Thus, prefabricated intermediates that
help in governing the target self-assemblies are developed into a type of unique
building blocks. Metal oxide cluster polyanions are considered as a type of
molecular nanoclusters with size scale and structural morphology similar to those
of many known inorganic particles and clusters but possess distinctive
characteristics. Following the understanding of these clusters in self-assembly
and the rationalization of their most efficient design strategy and approach, the
obtained fundamental principles can also be applied in common nanoparticle- and
cluster-based systems. On the other hand, the deliberate synergy offered by
organic countercations that support the self-assembly of these clusters greatly
expands the opportunity for the functionalization of complex building units via
control of multiple interactions. The ionic combination of the inorganic clusters
with hydrophilicity and the cationic organic component with hydrophobicity leads
to discrete properties of the complexes. Significantly, the core-shell structure
with rigid-flexible features and amphiphilicity will pave the way for
hierarchical self-assemblies of the obtained complexes, while the intrinsic
characteristics of the metal oxide clusters can be modulated through external
physicochemical stimuli. Within this context, over the past decade we have
extensively explored the ionic combination of inorganic polyanionic clusters with
cationic organic amphiphiles and devoted our efforts to establishing the general
rules and structure-property relationships of the formed complexes for
constructing self-assemblies at the interface, in solution, and in solid
matrixes. Specific interest has been focused on the functional synergy deriving
from the incompatible components in highly organized self-assemblies. In this
Account, we describe the recent progress on the ionic complexation of
polyoxometalate clusters with cationic amphiphiles and the construction of
diverse self-assembled nanostructures. First, the fundamental structural
characteristics and molecular geometries of the prepared complexes are analyzed.
The construction principle and diversity of the self-assembly based on the
complexes and the smart stimuli response are then discussed, subject to the
adjustment of various non-covalent interactions occurring in the assemblies.
Subsequently, we enumerate the functional applications of the ionic complexes
assembling into organic, inorganic, and even biological matrixes. The inspiration
from the construction of ionic complexation and self-assembly in this Account
provides vivid profiles for the design of hybrid materials involving nanoclusters
and/or nanoparticles with rich potentials in addition to polyoxometalate
chemistry.
PMID- 28508634
TI - Interfacial Metal-Oxide Interactions in Resistive Switching Memories.
AB - Metal oxides are commonly used as electrolytes for redox-based resistive
switching memories. In most cases, non-noble metals are directly deposited as
ohmic electrodes. We demonstrate that irrespective of bulk thermodynamics
predictions an intermediate oxide film a few nanometers in thickness is always
formed at the metal/insulator interface, and this layer significantly contributes
to the development of reliable switching characteristics. We have tested metal
electrodes and metal oxides mostly used for memristive devices, that is, Ta, Hf,
and Ti and Ta2O5, HfO2, and SiO2. Intermediate oxide layers are always formed at
the interfaces, whereas only the rate of the electrode oxidation depends on the
oxygen affinity of the metal and the chemical stability of the oxide matrix.
Device failure is associated with complete transition of short-range order to a
more disordered main matrix structure.
PMID- 28508635
TI - Polydopamine-Coated Manganese Carbonate Nanoparticles for Amplified Magnetic
Resonance Imaging-Guided Photothermal Therapy.
AB - This study reports a multifunctional nanoparticle (NP) that can be used for
amplified magnetic resonance image (MRI)-guided photothermal therapy (PTT) due to
its surface coating with a polydopamine (PDA) shell. Importantly, by means of
introducing the surface coating of PDA, large quantities of water can be trapped
around the NPs allowing more efficient water exchange, leading to greatly
improved MR contrast signals compared with those from NPs without the PDA
coating. Further, a distinct photothermal effect can be obtained arising from the
strong absorption of PDA in the near-infrared (NIR) region. By synthesizing
multifunctional MnCO3@PDA NPs, for example, we found that the longitudinal
relaxivity (r1) of MnCO3 NPs can improve from 5.7 to 8.3 mM-1 s-1. Subsequently,
in vitro MRI and PTT results verified that MnCO3@PDA could serve as an excellent
MRI/PTT theranostic agent. Furthermore, the MnCO3@PDA NPs were applied as an
MRI/PTT theranostic agent for in vivo MRI-guided photothermal ablation of tumors
by intratumoral injection in 4T1 tumor-bearing mice. The MR imaging result shows
a significantly bright MR image in the tumor site. The MnCO3@PDA-mediated PTT
result shows high therapeutic efficiency as a result of high photothermal
conversion efficiency. The present strategy of amplified MRI-guided PTT based on
PDA coating of NPs will be widely applicable to other multifunctional NPs.
PMID- 28508637
TI - Synthesis of Brominated Thiazoles via Sequential Bromination-Debromination
Methods.
AB - The synthesis of the full family of bromothiazoles has been revisited in order to
update and optimize their production. The species reported include 2
bromothiazole, 4-bromothiazole, 5-bromothiazole, 2,4-dibromothiazole, 2,5
dibromothiazole, 4,5-dibromothiazole, and 2,4,5-tribromothiazole, the majority of
which are produced via sequential bromination and debromination steps. This
complete family can now be produced without the use of elemental bromine, and the
presented methods have allowed the physical and NMR spectroscopic
characterization of the full family to be reported for the first time.
PMID- 28508636
TI - Piperazin-1-ylpyridazine Derivatives Are a Novel Class of Human dCTP
Pyrophosphatase 1 Inhibitors.
AB - The dCTP pyrophosphatase 1 (dCTPase) is a nucleotide pool "housekeeping" enzyme
responsible for the catabolism of canonical and noncanonical nucleoside
triphosphates (dNTPs) and has been associated with cancer progression and cancer
cell stemness. We have identified a series of piperazin-1-ylpyridazines as a new
class of potent dCTPase inhibitors. Lead compounds increase dCTPase thermal and
protease stability, display outstanding selectivity over related enzymes and
synergize with a cytidine analogue against leukemic cells. This new class of
dCTPase inhibitors lays the first stone toward the development of drug-like
probes for the dCTPase enzyme.
PMID- 28508638
TI - Determination of the Absolute Configuration of beta-Chiral Primary Alcohols Using
the Competing Enantioselective Conversion Method.
AB - A method for determining the absolute configuration of beta-chiral primary
alcohols has been developed. Enantioenriched alcohols were acylated in the
presence of either enantiomer of the enantioselective acylation catalyst HBTM,
and the faster reaction was determined by measuring product conversion using 1H
NMR spectroscopic analysis. An empirical mnemonic was developed that correlates
the absolute configuration of the alcohol to the faster reacting catalyst.
Successful substrates for this method include primary alcohols that bear a
"directing group" on the stereogenic center; directing groups include arenes,
heteroarenes, enones, and halides.
PMID- 28508639
TI - Polarizable and Non-Polarizable Force Field Representations of Ferric Cation and
Validations.
AB - The AMOEBA polarizable force field of ferric ion was optimized and applied to
study the hydration of ferric ion and its complexation with porphine in the
aqueous phase. The nonpolarizable force field was also optimized for comparison.
The AMOEBA force field was found to give a more accurate hydration free energy
than the nonpolarizable force field with respect to experimental data, and
correctly predict the most stable electronic state of hydrated Fe3+, which is the
sextet state, and of the Fe(III)-Por complex, which is the quartet state,
consistent with the literature that was carried out using the DFT method. The
explicit inclusion of charge transfer between Fe3+ and ligand was found to be
important in order to obtain a precise picture of polarization energy and van der
Waals energy, which otherwise deviate from the corresponding energy components
derived from ab initio calculations. The successful application of the AMOEBA
force field in the characterization of aquo Fe(III)-Por complexes suggests that
its use may be extended to the study of the dynamics of metalloenzyme containing
highly charged metal ions in the condensed phase with reliable treatment of the
interactions between metal atom and protein.
PMID- 28508640
TI - Construction of Polysubstituted 1,2-Dihydrocyclobuta[b]naphthalenes and 1,2
Dihydrocyclobuta[b]anthracenes with Photoluminescence.
AB - A facile protocol for the synthesis of polysubstituted 1,2
dihydrocyclobuta[b]naphthalenes and 1,2-dihydrocyclobuta[b]anthracenes was
developed via a sequence of base-promoted 1,5-H shift, intramolecular [2 + 2]
cycloaddition, and aromatization. The synthesized 1,2
dihydrocyclobuta[b]anthracenes exhibited bright blue emissions in solution and
strong yellow emissions in solid, which made them possible candidates for
optoelectronic conjugated materials.
PMID- 28508641
TI - Intramolecular, Site-Selective, Iodine-Mediated, Amination of Unactivated (sp3)C
H Bonds for the Synthesis of Indoline Derivatives.
AB - The Iodine-mediated oxidative intramolecular amination of anilines via cleavage
of unactivated (sp3)C-H and N-H bonds for the production of indolines is
described. This transition-metal-free approach provides a straightforward
strategy for producing (sp3)C-N bonds for use in the preferential
functionalization of unactivated (sp3)C-H bonds over (sp2)C-H bonds. The reaction
could be performed on a gram scale for the synthesis of functionalized indolines.
PMID- 28508642
TI - Identification of Alternative Splice Variants Using Unique Tryptic Peptide
Sequences for Database Searches.
AB - Alternative splicing is a mechanism in eukaryotes by which different forms of
mRNAs are generated from the same gene. Identification of alternative splice
variants requires the identification of peptides specific for alternative splice
forms. For this purpose, we generated a human database that contains only unique
tryptic peptides specific for alternative splice forms from Swiss-Prot entries.
Using this database allows an easy access to splice variant-specific peptide
sequences that match to MS data. Furthermore, we combined this database without
alternative splice variant-1-specific peptides with human Swiss-Prot. This
combined database can be used as a general database for searching of LC-MS data.
LC-MS data derived from in-solution digests of two different cell lines (LNCaP,
HeLa) and phosphoproteomics studies were analyzed using these two databases.
Several nonalternative splice variant-1-specific peptides were found in both cell
lines, and some of them seemed to be cell-line-specific. Control and apoptotic
phosphoproteomes from Jurkat T cells revealed several nonalternative splice
variant-1-specific peptides, and some of them showed clear quantitative
differences between the two states.
PMID- 28508644
TI - Normal, Leveled, and Enhanced Steric Effects in Alkoxyamines Carrying a beta
Phosphorylated Nitroxyl Fragment.
AB - The design of new R1R2NOR3 alkoxyamines for various applications relies on the
accurate prediction of two kinetic parameters, the C-ON bond homolysis rate
constant (kd) and its re-formation rate constant (kc). Relationships to describe
the steric and polar effects of the R1R2NO fragment ruling kd have been
developed. For all cyclic nitroxyl fragments, the steric effect is described as
the sum of the bulkiness of the R1 and R2 groups (i.e., normal steric effect),
while for the noncyclic nitroxyl fragment (except for one case), a leveled steric
effect is assumed. In this work, we show that the normal steric effect also
applies to noncyclic nitroxyl fragments and that for one case an enhanced steric
effect is also observed, i.e., experimental kd >5-fold larger than the predicted
value.
PMID- 28508643
TI - Correction to Enantio- and Diastereoselective Nitro-Mannich Reaction of alpha
Aryl Nitromethanes with Amidosulfones Catalyzed by Phase-Transfer Catalysts.
PMID- 28508645
TI - Pd(II)-Catalyzed Aerobic Intermolecular 1,2-Diamination of Conjugated Dienes: A
Regio- and Chemoselective [4 + 2] Annulation for the Synthesis of
Tetrahydroquinoxalines.
AB - A Pd(II)-catalyzed aerobic intermolecular 1,2-diamination of conjugated dienes
was developed for the regio- and chemoselective preparation of a variety of
functionalized tetrahydroquinoxalines, using simple sulfonyl protected o
phenylendiamines as a nitrogen source. This methodology provides a direct and
efficient synthesis of tetrahydroquinoxalines. O2 was used as the stoichiometric
oxidant, and reaction conditions were applied to a series of o-phenylendiamines
and conjugated dienes. 35 examples are described, and good yields and
selectivities are obtained for the majority of the products.
PMID- 28508646
TI - Synthesis of Spiropentadiene Pyrazolones by Rh(III)-Catalyzed Formal sp3 C-H
Activation/Annulation.
AB - A Rh-catalyzed enol-directed formal sp3 C-H activation/annulation of alpha
arylidene pyrazolones with alkynes has been developed. This reaction provides a
convenient route to synthesize spiropentadiene pyrazolones in good to excellent
yields at room temperature, exhibiting good functional group tolerance, gram
scalability, and high regioselectivity. Of note, the alpha-arylidene pyrazolone
was introduced as a novel C3 synthon in C-H activation/annulation.
PMID- 28508647
TI - Copper-Promoted Desulfitative N-Arylation of Sulfonamides and Sulfoximines with
Sodium Arylsulfinates.
AB - A general and direct N-arylation of sulfonamides and NH-sulfoximines by sodium
arylsulfinates through a desulfitative pathway was herein demonstrated. The
reaction proceeded with catalytic loadings of Cu(II)-catalysts without any
external ligands. And the novel arylation protocol featured for high efficiency
(up to 93% yields) and good substituent tolerance (up to 53 examples). Moreover,
a plausible reaction mechanism was also discussed.
PMID- 28508648
TI - Photoredox-Catalyzed Diamidation and Oxidative Amidation of Alkenes: Solvent
Enabled Synthesis of 1,2-Diamides and alpha-Amino Ketones.
AB - Photoredox-catalyzed difunctionalizations of alkenes with O-acyl hydroxylamine
derivatives are described. The solvent tunes the outcome of these reactions.
Diamidation and oxidative amidation of alkenes can be achieved in CH3CN and DMSO,
respectively. A variety of 1,2-diamidates and alpha-amino ketones bearing many
functional groups are prepared using Ir(ppy)3 as the photocatalyst under visible
light irradiation.
PMID- 28508650
TI - Correction to "Pd-Catalyzed Conversion of Aryl Iodides to Sulfonyl Fluorides
Using SO2 Surrogate DABSO and Selectfluor".
PMID- 28508649
TI - Colloidal Synthesis of Te-Doped Bi Nanoparticles: Low-Temperature Charge
Transport and Thermoelectric Properties.
AB - Electronically doped nanoparticles formed by incorporation of impurities have
been of great interest because of their controllable electrical properties.
However, the development of a strategy for n-type or p-type doping on sub-10 nm
sized nanoparticles under the quantum confinement regime is very challenging
using conventional processes, owing to the difficulty in synthesis. Herein, we
report the colloidal chemical synthesis of sub-10 nm-sized tellurium (Te)-doped
Bismuth (Bi) nanoparticles with precisely controlled Te content from 0 to 5% and
systematically investigate their low-temperature charge transport and
thermoelectric properties. Microstructural characterization of nanoparticles
demonstrates that Te ions are successfully incorporated into Bi nanoparticles
rather than remaining on the nanoparticle surfaces. Low-temperature Hall
measurement results of the hot-pressed Te-doped Bi-nanostructured materials, with
grain sizes ranging from 30 to 60 nm, show that the charge transport properties
are governed by the doping content and the related impurity and nanoscale grain
boundary scatterings. Furthermore, the low-temperature thermoelectric properties
reveal that the electrical conductivity and Seebeck coefficient expectedly change
with the Te content, whereas the thermal conductivity is significantly reduced by
Te doping because of phonon scattering at the sites arising from impurities and
nanoscale grain boundaries. Accordingly, the 1% Te-doped Bi sample exhibits a
higher figure-of-merit ZT by ~10% than that of the undoped sample. The synthetic
strategy demonstrated in this study offers the possibility of electronic doping
of various quantum-confined nanoparticles for diverse applications.
PMID- 28508651
TI - Sugar-Breathing Glycopolymersomes for Regulating Glucose Level.
AB - Diabetes mellitus is a chronic, life-threatening illness that affects people of
every age and ethnicity. It is a long-term pain for those who are affected and
must regulate their blood glucose level by frequent subcutaneous injection of
insulin every day. Herein, we propose a noninsulin and antidiabetic drug-free
strategy for regulating blood glucose level by a nanosized "sugar sponge" which
is a lectin-bound glycopolymersome capable of regulating glucose due to the
dynamic recognition between the lectin and different carbohydrates. The
glycopolymersome is self-assembled from poly(ethylene oxide)-block-poly[(7-(2
methacryloyloxyethoxy)-4-methylcoumarin)-stat-2-(diethylamino)ethyl methacrylate
stat-(alpha-d-glucopyranosyl)ethyl methacrylate] [PEO-b-P(CMA-stat-DEA-stat
GEMA)]. The lectin bound in the glycopolymersome has different affinity for the
glucose in the blood and the glucosyl group in the glycopolymersome. Therefore,
this sugar sponge functions as a glucose storage unit by dynamic sugar
replacement: The lectin in the sugar sponge will bind and store the glucose from
its surrounding solution when the glucose concentration is too high and will
release the glucose when the glucose concentration is too low. In vitro, this
sugar-breathing behavior is characterized by a remarkable size change of the
sugar sponge due to the swelling/shrinkage at high/low glucose levels, which can
be used for blood sugar monitoring. In vivo, this sugar sponge showed an
excellent antidiabetic effect for type I diabetic mice within 2 days upon one
dose, which is much longer than traditional long-acting insulin. Overall, this
concept of "controlling sugar levels with sugar" opens new avenues for regulating
the blood glucose level without the involvement of insulin or other antidiabetic
drugs.
PMID- 28508652
TI - New Infrared Bands of the C-Bonded Isomer of OC-N2O and Determination of Two
Intermolecular Frequencies.
AB - Three combination bands involving intermolecular modes of the most stable isomer
of the OC-N2O van der Waals complex have been observed, two in the carbon
monoxide CO stretch region (~2150 cm-1) and one in the nu3 asymmetric stretch
region of N2O (~2223 cm-1). Vibrational assignment is achieved by comparison with
data recently published ( Barclay , A. ; et al. Chem. Phys. Lett. 2016 , 62 , 651
), concerning OC-CO2. Two of these bands involve the same intermolecular mode,
one with the CO stretch and the other with the nu3 asymmetric stretch of N2O. The
values of intermolecular frequency deduced from these two bands agree very well,
showing no significant dependence on intramolecular vibrational excitation.
PMID- 28508653
TI - Synthesis and Reactivity of 5-Substituted Furfuryl Carbamates via
Oxanorbornadienes.
AB - Furfuryl carbamates are labile and require care to be accessed by activating
furfuryl alcohols. An alternative oxanorbornadiene (OND)-based strategy is
presented for the preparation of 5-R-substituted furfuryl carbamates via the
reactions of amines with intermediate OND carbonates. The resulting OND
carbamates, which are stable for several months, undergo thiol mediated retro
Diels-Alder reaction to deliver the desired furfuryl carbamates in a single
flask. Conditions for the selective hydrolysis of furfuryl carbamates in the
presence of tert-butyloxycarbonyl (Boc) groups were identified, and it was shown
that furfuryl carbamates can be used as a prodrug handle.
PMID- 28508654
TI - Asymmetric Transfer Hydrogenation of 1,3-Alkoxy/Aryloxy Propanones Using Tethered
Arene/Ru(II)/TsDPEN Complexes.
AB - A series of propanones containing combinations of aryloxy and alkoxy substituents
at the 1- and 3-positions were reduced to the alcohols via asymmetric transfer
hydrogenation using a tethered Ru(II)/TsDPEN catalyst. The enantioselectivities
of the reductions reveal a complex pattern of electronic and steric effects
which, when used in a matched combination, can lead to the formation of products
of up to 68% ee (84:16 er) from this highly challenging class of substrate.
PMID- 28508655
TI - [Prevention of eating disorders].
AB - The quality of the prevention of eating disorders represents in several last
decades frequently discussed issue in the context of rapidly changing socio
economic conditions, a significant increase of influence of the media, new
technologies and knowledge of risk factors. Primary prevention aims to reduce the
risk of developing eating disorders, but secondary and tertiary prevention play
the important role as well. Effective and coordinated prevention is still
missing. Our experience of international cooperation of the last 20 years led to
the development and evaluation of prevention programs. We are describing their
fast development and ongoing programs following the new trends recommended by
WHO.
PMID- 28508656
TI - [Prevention in psychiatry].
AB - Mental disorders affect annually about one-fifth of the population and represent
one of the biggest health burdens of the mankind in the 21st century. Despite
great achievements of drug therapy, biological therapy and psychotherapeutic
methods psychological problems in the present society are rather increasing.
Therefore, attention also focuses on primary prevention of mental disorders,
which is possible and effective.
PMID- 28508657
TI - [Suicide a serious health and social problem with the possibility of prevention].
AB - Suicide is a serious health and social problem whose incidence varies between
genders, age groups, geographical distribution and with influence of socio
political structure of society. It has been identified many risk factors and this
behavior has etiological heterogeneity. There is no effective algorithm to
predict suicidal activity in clinical practice, but increase the detection is
associated with introducing the professional community and especially primary
care physicians with clinical, psychological, sociological and biological factors
whose can bring increasing of the recognition of vulnerable individuals and allow
initiation of therapeutic interventions psychotherapy, psychopharmacology,
neuromodulatory modalities or their combinations to achieve effective level of
suicide prevention.
PMID- 28508658
TI - [Life style and affective disorders].
AB - Life style significantly affects the health status of each person. Life style
medicine is an evidence based practice, which is trying to develop patterns of
healthy behavior. Most evidence exists about the effect of suitable diet (eg.
unsaturated fatty acids) and adequate aerobic exercise. Combination of lifestyle
modification to standard psychopharmacologic and psychotherapeutic techniques can
improve the results of preventive and therapeutic programs for people with
depressive issues.
PMID- 28508659
TI - [Work-related stress and mental health - can work lead to mental disorders?]
AB - In the past two decades, special attention was paid to mental health issues. The
available literature suggests, for example, the relationship between the workload
and mental discomfort and the occurrence of myocardial infarction. This article
focuses mainly on the issue of work-related stress and its impact on mental
health. In this context, it must be acknowledged that possible psychological
problems due to work are not only employees problem. These difficulties can
significantly affect performance - and thus they should be the concern of the
employer, but also of customers, clients and patients who come into contact with
the worker who might develop some mental problems, due to the nature of his work
and working conditions. This article provides an overview of the various factors
affecting the mental health of employees. These are, for example, work demands,
working hours and workplace relations. In conclusion, it brings results of Czech
study examining job stress among working population.
PMID- 28508660
TI - [A note on application of the WHOQOL-BREF questionnaire on quality of life in the
Czech enviroment].
AB - In the Czech environment, the WHOQOL-BREF (WHO Quality of Life-BREF)
questionnaire has been rather frequently used for quality-of-life assessment in
the case of different diseases or different health limitations. The questionnaire
exists in two Czech translations with different wording. The differences are so
considerable that they might cause interpretation shifts in research based on
this instrument. Also the reverse scales in three questions may cause problems,
because processing of these scores is not described correctly in some
methodological materials. The authors recommend to strictly use the version
published by Dragomirecka and Bartonova of the Prague Psychiatric Centre.
PMID- 28508662
TI - Keeping Your Eyes Peeled for Corneal Ulcers.
PMID- 28508661
TI - Post-transplant lymphoproliferative disease in liver transplant recipients.
AB - INTRODUCTION: Post-transplant lymphoproliferative syndrome (PTLD) is a rare and
potentially life-threatening complication after liver transplantation. The aim of
this study was to analyze the clinicopathologic features related to PTLD in a
single institution after liver transplantation. METHODS: Observational study
where we have retrospectively analyzed 851 cases who underwent liver
transplantation. Ten cases have developed PTLD. Their clinical-pathological
characteristics and the treatment received have been analyzed. RESULTS: PTLD
incidence was 1.2% (10/851). The mean time from liver transplantation to PTLD
diagnosis was 36 months (range 1.2 to 144 months). PTLD localization was
extranodal in all cases, the most frequent location being intestinal. Seven cases
showed a monomorphic lymphoma which in all cases was differentiated B cell
lymphomas. Fifty per cent of the series were seropositive for Epstein-Barr virus.
Five patients were alive at the time of the review. Among these patients, we
observed three cases of complete remission and two cases of disease
stabilization. The death rate was higher in the first year after diagnosis of
PTLD. CONCLUSION: PTLD is a rare complication after liver transplantation, but it
may pose a threat to the life of a liver transplant recipient. It is essential to
identify patients at risk, to establish an early diagnosis and treatment that can
change the outcome of the disease.
PMID- 28508663
TI - 18F-FDG PET/CT in polymyalgia rheumatica-a pictorial review.
AB - Polymyalgia rheumatica (PMR) is one of the inflammatory rheumatic diseases that
can potentially be detected by positron emission tomography/CT. High fluorine-18
fludeoxyglucose (18F-FDG) accumulation around the shoulders, sternoclavicular and
hip joints are the most common pre-treatment features of patients with PMR.
Another common sign is increased 18F-FDG uptake in extra-articular regions
between columnal spinous processes, near ischial tuberosities and in the
praepubic area. Some patients also present with high 18F-FDG uptake in main
arteries, corresponding to the characteristics of giant cell arteritis. It is
possible to observe a decrease or even a disappearance of 18F-FDG uptake after
effective therapy, an event which may be useful for the monitoring of treatment
as well as for detection of PMR relapse.
PMID- 28508664
TI - Aphrodisiac Activity of the Aqueous Crude Extract of Purple Corn ( Zea mays) in
Male Rats.
AB - In the present study, the aphrodisiac properties of the purple corn ( Zea mays)
in male rats were analyzed. The aqueous crude extract of purple corn (at 25, 50,
and 75 mg/kg) was administered to ( a) copulating male rats and ( b) anesthetized
and spinal cord transected male rats. Behavioral parameters of copulatory
behavior and parameters of the genital motor pattern of ejaculation previous to
its inhibition, under the influence of the purple corn extract, are described.
Administration of the aqueous crude extract of purple corn significantly
facilitates the arousal and execution of male rat sexual behavior without
significant influences on the ambulatory behavior. In addition, purple corn
extract elicit a significant increase in the number of discharges of the
ejaculatory motor patterns and in the total number of genital motor patterns
evoked in spinal rats. The present findings show that the aqueous crude extract
of purple corn possesses aphrodisiac activity.
PMID- 28508665
TI - Prevalence of and risk factors for depressive symptoms among people living with
HIV/AIDS receiving antiretroviral treatment in Wuhan, China: a short report.
AB - We aimed to explore the prevalence of and risk factors for depressive symptoms
(DS) among people living with HIV/AIDS (PLWHA) receiving antiretroviral treatment
(ART) in Wuhan, Hubei, China. A cross-sectional study evaluating adult PLWHA
receiving ART in nine designated clinical hospitals was conducted from October to
December 2015. The validated Beck Depression Inventory (BDI) was used to assess
DS in eligible participants. Socio-demographical, epidemiological and clinical
data were directly extracted from the case reporting database of the China
HIV/AIDS Information Network. Multinomial regression analysis was used to explore
the risk factors for DS. 394 participants were finally included in all analyses.
40.3% were found to have DS with 13.7% having mild DS and 26.6% having moderate
to severe DS. The results of multinomial regression analysis suggested that being
married or living with a partner, recent experience of ART-related side effects,
and/or history of HCV infection were positively associated with mild DS, while
increasing age was positively associated with moderate to severe DS.
PMID- 28508666
TI - Biotransformation of total coumarins of Radix Glehniae by Lecanicillium
attenuatum W-1-9.
AB - The biotransformation of total coumarins of Radix Glehniae by Lecanicillium
attenuatum W-1-9 yielded three new products, lecaniside A (1), lecaniside B (2),
and lecaniside C (3). The chemical structures of these metabolites were
elucidated based on extensive spectral data, including 2D NMR and HRMS. The
hydrogenation, dealkylation, glycosylation, and O-methylation reactions of these
metabolites were observed in the present study. In the in vitro assays, compound
1 displayed a little PTP1B inhibitory activity.
PMID- 28508667
TI - Professionals' perspectives on a market-inspired policy reform: A guiding light
to the blind spots of measurement.
AB - Implementation of market-inspired competition and incentive models in health care
is increasing worldwide, assumed to drive efficiency. However, the evidence for
effects is mixed and unintended consequences have been reported. There is a need
to better understand the practical consequences of such reforms. The aim of the
present case study is to explore what consequences of a Swedish market-inspired
patient choice reform professionals identify as relevant, and why. The study was
designed as an explorative qualitative study in specialized orthopedics. Nineteen
interviews were conducted with health care professionals at different providers.
Data were analyzed using a hypo-deductive thematic approach. Consequences for the
organization of care, patients, work environment, education and research were
included in the professionals' analyses, covering both the perspective of their
own organization and that of the health care system as a whole. In sum, the
professionals provided multiple-level analyses that extended beyond the
responsibilities of their own organization. Concluding, professionals are a
valuable source of knowledge when evaluating policy reforms. Their analyses can
contribute by covering a broad system perspective, serving as a guiding light to
areas beyond the most obvious evaluation measures that should be included in more
formal evaluations.
PMID- 28508668
TI - Total synthesis and neuroprotective effect of O-methylmurrayamine A and 7
methoxymurrayacine.
AB - O-Methylmurrayamine A (7) and 7-methoxymurrayacine (8) are natural products
isolated from Murraya koenigii and Murraya siamensis, respectively. In this
paper, we report the synthesis of 7 and 8 which are featured in the key step of
cyclization to form carbazole intermediate 5 with mild conditions. The structures
were confirmed by 1H NMR, 13C NMR, and HR-ESI-MS. In addition, compounds 7 and 8
were tested for their neuroprotective effects against H2O2-induced PC12 cell
damage. The results showed that compounds 7 and 8 have neuroprotective effect.
PMID- 28508669
TI - Efficient discrimination and removal of phospholipids during electromembrane
extraction from human plasma samples.
AB - AIM: For the first time, extracts obtained from human plasma samples by
electromembrane extraction (EME) were investigated comprehensively with
particular respect to phospholipids using ultra-high-performance liquid
chromatography tandem mass spectrometry (UHPLC-MS/MS). Thhe purpose was to
investigate the potential of EME for phospholipid cleanup in different EME
systems. RESULTS & DISCUSSION: No traces of phospholipids were detected in any of
the acceptor solutions, whereas the model analytes were extracted with recoveries
up to 50%. Thus, the EME systems tested in this work were found to be highly
efficient for providing phospholipid-free extracts. CONCLUSION: Ultra-HPLC-MS/MS
analysis of the donor solutions revealed that the phospholipids principally
remained in the plasma samples. This proved that the phospholipids did not
migrate in the electrical field and they were prevented from penetrating the
supported liquid membrane.
PMID- 28508670
TI - Why did Sigmund Freud refuse to see Pierre Janet? Origins of psychoanalysis:
Janet, Freud or both?
AB - Pierre Janet and Joseph Breuer were the true originators of psychoanalysis. Freud
greatly elaborated on their findings. Freud initially admitted these facts but
denied them in later life. Janet discovered the concept transference before
Freud.
PMID- 28508671
TI - Chemometric profile, antioxidant and tyrosinase inhibitory activity of Camel's
foot creeper leaves (Bauhinia vahlii).
AB - The present study is the first effort to a comprehensive evaluation of
antityrosinase activity and chemometric analysis of Bauhinia vahlii. The
experimental results revealed that the methanol extract of Bauhinia vahlii (BVM)
possesses higher polyphenolic compounds and total antioxidant activity than those
reported elsewhere for other more conventionally and geographically different
varieties. The BVM contain saturated fatty acids such as hexadecanoic acid
(10.15%), octadecanoic acid (1.97%), oleic acid (0.61%) and cis-vaccenic acid
(2.43%) along with vitamin E (12.71%), alpha-amyrin (9.84%), methyl salicylate
(2.39%) and beta-sitosterol (17.35%), which were mainly responsible for
antioxidant as well as tyrosinase inhibitory activity. Tyrosinase inhibitory
activity of this extract was comparable to that of Kojic acid. These findings
suggested that the B. vahlii leaves could be exploited as potential source of
natural antioxidant and tyrosinase inhibitory agent, as well.
PMID- 28508672
TI - Assessing infant-oriented care with developmental support approach in Iranian
NICUs.
AB - INTRODUCTION: Developmental care program is a comprehensive program to reduce
secondary effects of NICU and special care on brain development in premature
infants. This study aimed to assess neonatal care situation in Iranian NICUs
based on developmental approach to design and provide clinical guidelines for
daily care for the caregivers and the infant's family. METHODS: This was a cross
sectional study conducted in NICUS in Iran. A total of 23 NICUs of 9 Universities
of Medical Sciences were investigated. The checklist contains 30 items in 6
domains. Data were analyzed using STATA software, version 13. RESULTS: The total
mean score obtained from all six domains was 31.29 of 100, and in all domains,
the mean scores calculated were not above 50. In "supporting infant,"
"developmental caregiving activities," "supporting the infants' state
organization," "providing neonatal pain management," "developmental care
approaches in documentation," and "developmental care approaches in NICU
staffing," the total mean scores were 34.76, 21.6, 20, 30.18, 31.30, and 50,
respectively. CONCLUSION: The low mean score of infant-centered developmental
care implies health staff's focus on neonatal care with at least the quality of
care and its impact on development in preterm infants, and inadequate attention
to the infant as an active member in care.
PMID- 28508673
TI - Ayurvedic college education, reifying biomedicine and the need for reflexivity.
AB - The paper analyses the experiences with government sanctioned Ayurvedic college
education of 14 young Ayurvedic doctors working at the Integrative Health Centre
in Bangalore, India. Unfamiliarity with Ayurvedic logic and Indian natural
philosophies, lack of clinical training and the mixing-up of Ayurvedic and
biomedical notions are their main complaints. The 14 young Ayurvedic doctors also
missed a convincing perspective on how to integrate Ayurvedic logic, modern
scientific knowledge and biomedical diagnostics. Ayurvedic state sanctioned
education seems to be caught between Ayurveda's natural philosophy of health and
the techno-science of biomedicine. The Ayurvedic doctors under scrutiny face the
danger of becoming 'half-baked products' when they do not learn to reflect on the
tension between Indian traditional knowledge and biomedical learning. The paper
argues that the logic of modern science and biomedicine's claim to value-free
knowledge captivates Ayurvedic education and research. This hinders Ayurveda's
development as a vibrant alterity to biomedicine. What is needed is a critical
social science perspective on the construction of medical knowledge and India's
hierarchical medical landscape.
PMID- 28508674
TI - Psychosocial screening and monitoring for children in foster care: Psychometric
properties of the Brief Assessment Checklist in a Dutch population study.
AB - Children in foster care experience higher levels and rates of psychosocial
difficulties than children from the general population. Governments and child
welfare services have a responsibility to identify those children in care who
have need for therapeutic services. This can be achieved through systematic
screening and monitoring of psychosocial difficulties among all children in
foster care. However, general screening and assessment measures such as the
Strengths and Difficulties Questionnaire (SDQ) and Child Behavior Checklist
(CBCL) might not adequately screen for the range of difficulties experienced by
foster children. The Brief Assessment Checklists for Children (BAC-C) and Brief
Assessment Checklists for Adolescents (BAC-A) are measures designed to screen for
and monitor attachment- and trauma-related difficulties among child welfare
populations. This article reports psychometric properties of the BAC-C and BAC-A,
estimated in a population study of 219 Dutch foster children. The results suggest
the BAC-C and BAC-A perform both screening and monitoring functions well. Their
screening accuracy, internal reliability and concurrent validity are comparable
to those estimated for the SDQ within the same child and adolescent sample.
Future research is needed to assess the value of the Brief Assessment Checklists
(BAC) compared to other measures and to validate cut-points for the BAC. This
study further establishes the BAC-A and BAC-C as valid and useful mental health
screening and monitoring measures for use with children and adolescents in foster
care.
PMID- 28508675
TI - Serious mental illness among young adult women who use drugs in the club scene:
co-occurring biopsychosocial factors.
AB - Young women who regularly attend nightclubs are at risk for numerous health and
social consequences, including mental distress, sexual and physical victimization
and substance dependence. This paper uses a biopsychosocial framework to examine
co-occurring mental health problems, victimization, substance dependence, sexual
risk and physical pain among a sample of young women who use drugs (N = 222) in
Miami's club scene. The majority of women were under 24 years old, Hispanic, and
identified as heterosexual. Almost all the women reported past 90-day use of
alcohol, ecstasy/MDMA, marijuana, cocaine and prescription opioids and
benzodiazepines; 32% of women reported being in a monogamous relationship while
41.9% reported having three or more sexual partners in the past 90 days; 65.3%
met DSM-IV criteria for substance dependence; 60.4% met DSM-IV criteria for
serious mental illness (SMI) and 59.9% were victimized as minors. Women who had
SMI had higher odds of substance dependence, concurrent physical pain, three or
more sexual partners in the past 90 days, childhood victimization and severe
abuse-related trauma. The high levels of interconnected mental health,
victimization, trauma, physical pain, substance dependence and sexual risk
factors observed are underreported in the literature, as young women club scene
participants appear to be more similar to other marginalized drug-involved
populations than previously considered. While further research is needed, it
appears these young women are in great need of outreach for primary health,
mental health, HIV prevention, increased social support and substance abuse
treatment services.
PMID- 28508676
TI - Two new compounds from the fruiting bodies of Ganoderma philippii.
AB - Two new compounds, philippin (1) and 3beta,9alpha,14alpha-trihydroxy-(22E,24R)
ergost-22-en-7-one (2), were isolated from the fruiting bodies of Ganoderma
philippii. Their structures were elucidated on the basis of the spectroscopic
technologies, including 1D and 2D NMR as well as MS. The bioassay of inhibitory
activity against acetylcholinesterase (AChE) showed compound 1 exhibited weak
inhibitory activity against AChE.
PMID- 28508677
TI - Ketonuria may be associated with low serum amylase independent of body weight and
glucose metabolism.
AB - CONTEXT: Ketonuria, which reflects a preferential combustion of lipids relative
to carbohydrates, is often observed in lean rather than obese people. Clinical
studies have shown that individuals with diabetes and/or obesity predispose to
have low serum amylase (LSA). OBJECTIVE: To investigate the association between
ketonuria and LSA. METHODS: We examined ketonuria assessed by dipstick urinalysis
and clinical parameters including serum amylase in 3638 Japanese people aged 25
79 years who underwent a health-screening checkup. RESULTS: There was an inverse
relationship between body mass index (BMI) and serum amylase. The lowest serum
amylase was observed in obese subjects (BMI >= 25.0 kg/m2) with positive
ketonuria. Logistic regression analysis showed that ketonuria was significantly
associated with LSA (<50 IU/L), which was not altered by the adjustments for
relevant confounders including age, sex, BMI, and HbA1c. CONCLUSIONS: Current
results suggest a relative unavailability of carbohydrates for energy production
in individuals with LSA.
PMID- 28508678
TI - Past is prologue: how to advance caregiver interventions.
AB - OBJECTIVES: Research on caregiving interventions has increased substantially in
recent years. Although many promising approaches have been tested, results are
often modest. The goal of this paper is to identify conceptual and methodological
issues that could lead to better treatment outcome. METHOD: A critical review of
the literature on interventions for caregivers of persons with dementia. RESULTS:
A fundamental issue in caregiver interventions is what are appropriate goals for
treatment and what outcome measures should be used to address those goals. There
also needs to be more testing of the mechanisms by which treatment leads to
improvement. Intervention studies should also more regularly examine fidelity of
treatment implementation. CONCLUSION: Recommendations are made for improving the
design of future trials through better attention to the heterogeneity of the
caregiving population, improved conceptualization of goals and the use of
innovative designs that accommodate differences in caregivers' needs and
resources.
PMID- 28508679
TI - Comparison of FDG PET metabolic tumour volume versus ADC histogram: prognostic
value of tumour treatment response and survival in patients with locally advanced
uterine cervical cancer.
AB - OBJECTIVE: To evaluate the prognostic utility of volume-based parameters of
fluorine-18 fludeoxyglucose positron emission tomography (18F-FDG PET) and
apparent diffusion coefficient (ADC) histogram analysis for tumour response to
therapy and event-free survival (EFS) in patients with uterine cervical cancer
receiving chemoradiotherapy. METHODS: The study included 21 patients diagnosed
with locally advanced uterine cervical cancer who underwent pre-treatment MRI and
18F-FDG PET and were treated with concurrent chemoradiotherapy. 18F-FDG
parameters: maximum and mean standardized uptake value; metabolic tumour volume
(MTV); total lesion glycolysis (TLG); ADC parameters: maximum, mean and minimum
values; percentile ADC values (10-90%); skewness and kurtosis of ADC were
measured and compared between the responder and non-responder groups using a
Wilcoxon rank-sum test. The Cox regression analysis and Kaplan-Meier survival
curves were performed for EFS analysis. RESULTS: MTV and TLG of the primary
tumour were significantly higher in the non-responder group than in the responder
group (p = 0.04 and p = 0.01). Applying Cox regression multivariate analysis, MTV
[hazard ratio (HR), 4.725; p = 0.036], TLG (HR, 4.725; p = 0.036) and 10
percentile ADC (HR, 5.207; p = 0.048) showed a statistically significant
association with EFS. With the optimal cut-off value, the EFS rates above the cut
off value for MTV and TLG were significantly lower than that below the cut-off
value (p = 0.002 and p = 0.002). CONCLUSION: Pre-treatment volume-based
quantitative parameters of 18F-FDG PET may have better potential than ADC
histogram for predicting treatment response and EFS in patients with locally
advanced cervical cancer. Advances in knowledge: In this study, pre-treatment
volume-based quantitative parameters of 18F-FDG PET had better potential than ADC
histogram for predicting treatment response and survival in patients with locally
advanced cervical cancer.
PMID- 28508681
TI - Correction to: Abhishek et al., Antioxidant and anti-inflammatory activities of
Aerva pseudotomentosa leaves.
PMID- 28508680
TI - Personality and destiny. Francesco Borromini: portrait of a tormented soul.
AB - Francesco Borromini, one of the great geniuses of Baroque architecture, was
tormented and solitary, and was increasingly frustrated by the fame and success
of his rival, Gian Lorenzo Bernini. Borromini was an unhappy man, constantly
dogged by disaster, quarrelling even with his best patrons and closest friends.
In the culmination of one of the fits of depression that overcame the architect
more and more frequently as his life progressed, Borromini literally fell on his
own sword; he lingered in excruciating pain for 24 hours before dying. Largely
forgotten, his architecture has again been recognized since the twentieth century
as the creation of genius. We try to describe the personality and suicide of this
pessimist giant of architecture.
PMID- 28508682
TI - The risk of non-union per fracture: current myths and revised figures from a
population of over 4 million adults.
AB - Background and purpose - Fracture non-union remains a major clinical problem, yet
there are no data available regarding the overall risk of fractures progressing
to non-union in a large population. We investigated the rate of non-union per
fracture in a large adult population. Methods - National data collected
prospectively over a 5-year period and involving just under 5,000 non-unions were
analyzed and compared to the incidence of fracture in the same period. Results
and interpretation - The overall risk of non-union per fracture was 1.9%, which
is considerably less than previously believed. However, for certain fractures in
specific age groups the risk of non-union rose to 9%. As expected, these higher
rates of non-union were observed with tibial and clavicular fractures, but-less
expectedly-it was in the young and middle-aged adults rather than in the older
and elderly population. This study is the first to examine fracture non-union
rates in a large population according to age and site, and provides more robust
(and lower) estimates of non-union risk than those that are frequently quoted.
PMID- 28508683
TI - Effectiveness of mild ovarian stimulation versus GnRH agonist protocol in women
undergoing assisted reproductive technology: a meta-analysis.
AB - OBJECTIVE: our meta-analysis was conducted to evaluate the effectiveness of the
mild ovulation induction protocol using CC/gonadotropin/GnRH antagonist compared
to the conventional GnRH agonist protocol in women undergoing ART. METHOD: Six
electronic databases were searched from their date of establishment until August
2016. Outcomes in our analysis were calculated in terms of relative risk (RR) and
weighted mean differences (WMD) and standard mean differences (SMD) with 95%
confidence intervals (CI) using random effect models or fixed effect models.
RESULTS: Six prospective controlled clinical trials with 1543 women comparing the
clinical impacts of the two protocols were included. The synthesized results
suggested a significant reduction in the quantity of gonadotropins (SMD: -1.96,
95% CI: -2.28 to 1.64, I2 = 78.5%), the incidence of OHSS (RR: 0.16, 95% CI 0.03
0.86, I2 = 0%) and an increase in the cycle cancelation rate (RR: 1.46, 95% CI
1.05-2.03, I2 = 89.4%). While no evidence of statistically significant
differences between the groups existed in the other clinical outcomes.
CONCLUSION: This study suggested that the probable benefits of the mild protocol,
including its less costs and safer process without reducing the overall IVF
treatment success rates, seemed to make it a better treatment option. Larger
sample prospective trials evaluating live birth, clinical pregnancy, OHSS,
multiple pregnancy incidence and so on were desired to establish.
PMID- 28508684
TI - Cutaneous Mixed Tumor and Recurrent Laryngeal Squamous Cell Carcinoma With
Tyrosine-Rich Crystalloids: The Good, the Bad, and the Pretty.
PMID- 28508685
TI - Primary Epidermoid Cyst of Biliary Duct Presenting as Choledochal Cyst.
AB - Choledochal cyst is a cystic dilation of the biliary tree that can increase the
risk of malignancy in bile ducts and the gallbladder. These are usually lined by
bile duct epithelium, which may undergo intestinal and squamous metaplasia. This
is the first report of clinically diagnosed type II choledochal cyst that is
entirely lined by metaplastic stratified squamous epithelium, unlike most other
cysts, which are histologically lined by bile duct epithelium. This observation
can potentially explain the underlying pathogenic mechanism of rare reports of
squamous cell carcinomas arising in bile duct systems.
PMID- 28508686
TI - Malignant Peripheral Nerve Sheath Tumor of the Femur: A Rare Diagnosis Supported
by Complete Immunohistochemical Loss of H3K27me3.
AB - The histological diagnosis of malignant peripheral nerve sheath tumor (MPNST) is
challenging because of the wide morphological spectrum and suboptimal performance
of conventional immunohistochemical markers. MPNST arising primarily in the bone
is exceptional, and its definitive diagnosis, particularly out of the
neurofibromatosis type 1 (NF1) context, is even more problematic. Recurrent
inactivation of EED or SUZ12 in a majority of MPNSTs results in a complete loss
of trimethylated histone H3 at lysine 27 (H3K27me3) immunoreactivity, making it a
highly specific biomarker of MPNSTs. In this article, we report a case of
sporadic MPNST of the proximal femur that showed complete loss of H3K27me3. The
patient was treated with limb-sparing surgery and postoperative radiotherapy. He
developed multiple lung and bone metastases 4 months after surgery. Our case
confirms the utility of H3K27me3 immunohistochemistry to yield a definitive
diagnosis of sporadic MPNST in a rare primary site.
PMID- 28508687
TI - Multilocular Thymic Cyst With Mucinous Differentiation: A Mimicker of Thymic
Mucoepidermoid Carcinoma.
PMID- 28508688
TI - Extrarenal Wilms Tumor With Skeletal and Glial Differentiation.
PMID- 28508689
TI - Age, choline-to-N-acetyl aspartate, and lipids-lactate-to-creatine ratios
assemble a significant Cox's proportional-hazards regression model for survival
prediction in patients with high-grade gliomas.
PMID- 28508690
TI - Gene polymorphisms associated with temperament.
AB - When individuals are exposed to stressful environmental challenges, the response
varies widely in one or more of three components: psychology, behavior and
physiology. This variability among individuals can be defined as temperament. In
recent years, an increasing large body of evidence suggests that the dimensions
of temperament, as well as personality, psychological disorders and behavioral
traits, are influenced by genetic factors, and much of the variation appears to
involve variation in genes or gene polymorphisms in the hypothalamic-pituitary
adrenocortical (HPA) axis and the behavior-controlling neurotransmitter networks.
Here, we review our current understanding of the probabilistic impact of a number
of candidate gene polymorphisms that control temperament, psychological disorders
and behavioral traits in animals and human, including the gene polymorphisms
related to corticotrophin-releasing hormone (CRH) production and adrenal cortisol
production involved in the HPA axis, and a large number of gene polymorphisms in
the dopaminergic and serotonergic neurotransmitter networks. It will very likely
to assist in diagnosis and treatment of human relevant disorders, and provide
useful contributions to our understanding of evolution, welfare and conservation,
for animals in the wild and in production systems. Additionally, investigations
of gene-gene and gene-environment complex interactions in humans and animals need
further clear illustration.
PMID- 28508691
TI - Corifollitropin alfa compared with follitropin beta in GnRH-antagonist ovarian
stimulation protocols in an unselected population undergoing IVF/ICSI.
AB - Recombinant DNA technologies have produced Corifollitropin alfa (CFa) used during
IVF/ICSI in order to keep the circulating FSH levels above the threshold
necessary to support multi-follicular growth for a week. In this prospective case
control study, we compared 70 participants treated with 150 MUg CFa combined with
150 IU of follitropin beta (study group) with 70 subfertile participants with
matching baseline characteristics, conforming with the same inclusion criteria
and treated with an antagonist protocol using follitropin beta (control group).
Live birth was the primary outcome, while secondary outcome measures were
IVF/ICSI cycles characteristics, including adverse events and complications. Live
birth was determined in reduced rates in the study compared to the control group,
reaching statistical significance [6/70 versus 20/70, p = 0.002], as also in the
respective number of clinical pregnancies [9/70 versus 23/70, p = 0.005],
although the incidence of miscarriage was similar for both groups [6/70 versus
5/70, p > 0.99]. Most of the secondary parameters examined were similar between
groups. Logistic regression revealed that protocol and AFC had a direct impact on
live birth. Ovarian stimulation with CFa does not seem to constitute an equally
effective method as compared with follitropin beta to be offered in a general
subfertile population seeking IVF/ICSI treatments.
PMID- 28508693
TI - A metabolite profiling method for diagnosis of precancerous cervical lesions and
HPV persistence.
AB - AIM: With the advent of rapid metabolic profiling techniques and of portable mass
spectrometers we examined whether cells distinguished by their cytology and
persistence of human papillomavirus infection, could be easily differentiated by
their metabolite profile. MATERIALS & METHODS: Direct injection electrospray mass
spectrometry was used in a nontargeted double-blind experiment. Samples were
collected from women diagnosed with one of two grades of cervical cytology and
exhibiting either human papilloma virus persistence or clearance. Cell extracts
were prepared using a DNA extraction procedure and the resulting supernatant,
normally discarded, was analyzed. Data were interpreted using principal component
analysis. RESULTS: The results indicate strongly that a simple metabolite
profiling method could be used to rapidly identify women at increased risk of
cervical cancer.
PMID- 28508692
TI - SEIFEM 2010-E: economic evaluation of posaconazole for antifungal prophylaxis in
patients with acute myeloid leukemia receiving induction chemotherapy.
AB - Posaconazole demonstrated clinical superiority over fluconazole and itraconazole
for prophylaxis of mold infections, although concerns exist regarding the high
acquisition cost for posaconazole. In this respect, we sought to analyze the
costs of antifungal prophylaxis in patients with acute myeloid leukemia (AML) who
received prophylactic posaconazole (n = 510, 58%), itraconazole (n = 120, 14%) or
fluconazole (n = 175, 20%) during induction chemotherapy. The estimated cost of
antifungal prophylaxis as well as the costs of subsequent systemic antifungal
therapy for treatening an invasive fungal infections (IFI) was higher in the
posaconazole group compared to itraconazole and fluconazole groups. Based on the
Monte Carlo simulations, the itraconazole group had the highest cost, followed by
the posaconazole and fluconazole group, although the overall survival was higher
in the posaconazole group as compared to the other groups. In conclusion, the
cost of prophylaxis with posaconazole in AML patients compares favorably with
conventional antifungal agents.
PMID- 28508694
TI - Online versus offline spatiotemporal image correlation (STIC) M-mode for the
evaluation of cardiac longitudinal annular displacement in fetal growth
restriction.
AB - PURPOSE: Our first aim was to compare online M-mode with offline spatiotemporal
image correlation (STIC) M-mode for assessing longitudinal annular displacement
(LAD) in growth-restricted fetuses (FGR). Our second aim was to compare LAD
measures of FGR cases with controls. MATERIALS AND METHODS: Prospective study
including 40 FGR cases (defined estimated fetal weight and birth weight <10th
centile) and 72 normally grown fetuses matched to cases by gestational age at
scan. LAD was measured with online M-mode and offline STIC M-mode at the left and
right ventricular free walls and septum in all fetuses. RESULTS: FGR cases had a
significant decrease in LAD by STIC in all sites as compared to controls (e.g.
right LAD in FGR mean 6.7 mm (SD 1.2) versus controls 7.2 mm (1.2), p = .033).
There was a non-significant trend for lower values in FGR when using online M
mode (e.g. right LAD in FGR 6.9 mm (1.5) versus controls 7.4 mm (1.5), p = .084).
CONCLUSIONS: STIC M-mode seems a better method than online M-mode for detecting
subtle changes in myocardial motion. STIC presents more precise results and
allows an ideal placement of the M-mode arrow. These results confirm previous
data suggesting decreased longitudinal motion in FGR.
PMID- 28508695
TI - Ganglion Cells Are Frequently Present in Pediatric Mucosal Colorectal Biopsies:
H&E Sections and Calretinin Immunohistochemistry in the Evaluation of Children
With Chronic Constipation.
AB - Hirschsprung disease (HD) rarely presents as chronic constipation after the
newborn period. At our institution, calretinin immunohistochemistry (CAL) is
frequently requested by clinicians on rectal mucosal biopsies (RMBs) taken during
colonoscopy in older children in whom suspicion for HD is low. We hypothesized
that review of these biopsies would frequently reveal ganglion cells (GCs). We
reviewed features of mucosal biopsies (November 2013 to September 2015) from
children >=1 year of age on which clinicians had requested CAL on at least one
specimen. A total of 93 biopsies with paired CAL from 83 patients were suitable
for study (ages 1-18 years, M:F 1.2). Submitted clinical indication was
constipation in 62 patients (75%). GCs were found within or subjacent to
muscularis mucosa in 63 biopsies (68%), 12 (19%) of which were designated from a
specific anatomic site, eg, 2 or 3 cm. In 25 of 63 (40%) cases, GCs were
identified on one of the first 3 sections (median 5th, range 1st-54th). Forty-six
cases (73%) contained no or <0.5 mm of submucosa (SM, range 0-2 mm). All but one
case (62/63, 98%) with identified GCs showed positive CAL staining; a single case
showed equivocal staining. Among the 30 biopsies with no observed GCs, none (0%)
had >1 mm of SM, and 21 (70%) had no SM. CAL was positive in 28 (93%) and
equivocal/weak in 2 (7%); no additional work-up for HD was pursued. The data
suggest that H&E sections of RMBs can exclude HD at a specified site in many
cases and provide the basis for a future study examining the utility of CAL in
RMBs without SM as a means for excluding HD.
PMID- 28508696
TI - A bibliometric analysis of occupational therapy publications.
AB - BACKGROUND: Bibliometrics involves the statistical analysis of the publications
in a specific discipline or subject area. A bibliometric analysis of the
occupational therapy refereed literature is needed. AIM: A bibliometric analysis
was completed of the occupational therapy literature from 1991-2014, indexed in
the Science Citation Index-Expanded or the Social Sciences Citation Index.
METHOD: Publications were searched by title, abstract, keywords, and KeyWords
Plus. Total number of article citations, citations per journal, and contributions
per country, individual authors, and institution were calculated. RESULTS: 5,315
occupational therapy articles were published in 821 journals. It appears that
there is a citation window of an approximate 10-year period between the time of
publication and the peak number of citations an article receives. The top three
most highly cited articles were published in Developmental Medicine and Child
Neurology, JAMA, and Lancet. AJOT, BJOT and AOTJ published the largest number of
occupational therapy articles with the United States, Australia, and Canada
producing the highest number of publications. McMaster University, the University
of Queensland, and the University of Toronto were the institutions that published
the largest number of occupational therapy journal articles. CONCLUSION: The
occupational therapy literature is growing and the frequency of article citation
is increasing.
PMID- 28508697
TI - Collagen concentration on the facial skin of postmenopausal women after topical
treatment with estradiol and genistein: a randomized double-blind controlled
trial.
AB - OBJECTIVE: The objective of this study is to compare the effects of topical
estrogen and genistein (a soy isoflavone) on the facial skin collagen of
postmenopausal women not undergoing systemic hormonal therapy. METHODS: This is a
prospective, double blind, randomized, controlled clinical trial. Volunteer women
(N = 30) 45-55 year old from the Endocrine Gynecology sector of the Gynecology
Department of the Federal University of Sao Paulo (UNIFESP). The Ethical
Committee of the Federal University of Sao Paulo approved the study (report no.
386/2004; registration on ClinicalTrials.gov NCT01553773), were assigned to
topical treatment with either estrogen or genistein for 24 weeks. We quantified
and compared facial collagen concentration before and after each treatment by
performing pre-auricular skin biopsies. RESULTS: Our data showed an increase in
the amount of both type I and type III facial collagen by the end of both
treatments. However, the outcomes of the estrogen GI (ER) group were superior to
the genistein GII (GEN) group, with statistical significance p < 000.1
Conclusion: Treatment with topical estrogen is superior to genistein, but both
have positive impacts on facial skin collagen. Nevertheless, it is still unclear
whether prolonged use of genistein and other topical phytoestrogens could produce
systemic effects and further research is needed to clarify this question.
PMID- 28508698
TI - Negative impact of litigation procedures on patient outcomes four years after
severe traumatic brain injury: results from the PariS-traumatic brain injury
study.
AB - PURPOSE: To analyze the effect of litigation procedures on long-term outcomes in
severe traumatic brain injury. MATERIALS AND METHODS: Prospective observational
follow-up of an inception cohort including 504 adults with severe traumatic brain
injury recruited in 2005-2007 in the Parisian area, France, with initial, one-
and four-year outcomes measures. RESULTS: Four years after the traumatic brain
injury, 147 patients, out of 257 who survived the acute phase, were assessed.
Among these patients, 53 patients declared being litigants and 78 nonlitigants
(litigation status was unknown in 16 cases). Sociodemographic characteristics,
type of injury and initial severity did not differ significantly between
litigants and nonlitigants, except for Injury Severity Score (worse in litigants)
and the proportion of road traffic accidents (higher in litigants). One- and four
year outcomes were significantly worse in litigants for autonomy, participation,
psychiatric and cognitive function but not quality of life (measured with the
Glasgow Outcome Scale-Extended, the working activity status, the Brain Injury
Community Rehabilitation Outcome, the Hospital Anxiety and Depression scale, the
Neurobehavioral Rating Scale-revised and the Quality of Life after Brain Injury,
respectively). Multivariate analyses highlighted litigation procedure as an
independent significant predictor of lower autonomy, participation and
psychiatric function and tended to predict lower cognitive function, but not
lower quality of life, after adjustment for pretrauma characteristics, Injury
Severity Score, road traffic accidents and work-related accident status.
CONCLUSIONS: Patients with severe traumatic brain injury have a worse prognosis
when involved in a litigation procedure and require special attention in clinical
practice. Implications for rehabilitation The influence of litigation procedure
on health and social outcomes in severe traumatic brain injury is a major issue
that entail numerous levels of complexities. A wide range of interactions and
factors related to the prolonged process of litigation against a third party may
influence recovery. Results from the PariS-Traumatic Brain Injury study suggest
that patients with a severe Traumatic Brain Injury who are involved in a
litigation procedure within French jurisdiction compensation scheme have a worse
prognosis than patients who do not. Health professionals should be aware of the
potential adverse effects of litigation procedures on recovery, and provide
appropriate interventions and information to patients and families in such cases.
PMID- 28508701
TI - Beyond 'invisibility': queer intelligibility and symbolic annihilation in
healthcare.
AB - Sexual minority health is increasingly receiving attention by health sciences
education and healthcare, with the core argument being that health can be
improved by challenging sexual minority invisibility. Invisibility as a concept,
however, does not allow for a deeper theoretical engagement with the reasons and
consequences of the lack of representation of queerness in healthcare. Drawing on
empirical research with queer healthcare users in South Africa, I argue that
'invisibility' actually encompasses two distinct, though related, concepts: queer
symbolic annihilation as the reason for the exclusion of queer identities in
health professions education and, by consequence, in healthcare; and queer
(un)intelligibility as the consequence of this systemic erasure. By simply
attributing discriminatory healthcare experiences of queer people to
'invisibility' we are missing opportunities to address underlying issues of queer
symbolic annihilation and unintelligibility.
PMID- 28508700
TI - The Chronicity of Depressive Symptoms in Mothers of Children With Asthma.
AB - Depression can disproportionately affect low-income women. The purpose of this
study was to explore the chronicity of depressive symptoms in a sample of 276 low
income inner-city mothers of children with high-risk asthma. The aims were to
identify factors (asthma health status, stress, social support) associated with
change in depressive symptomatology over 12 months as well as to ascertain what
factors are most consistently associated with depressive symptoms. Using latent
growth curve analysis, demographic variables, asthma severity, stress, and social
support failed to explain changes in depressive symptomatology. The growth curve
models, however, were predictive of Center for Epidemiologic Studies-Depression
Scale (CES-D) scores at distinct time points indicating that higher daily stress
and lower social support were associated with increased depressive symptoms. Our
data highlight the chronic nature of depressive symptoms in low-income mothers of
children with poorly controlled asthma. Integrating questions about caregiver
psychological state across all clinical encounters with the family may be
indicated.
PMID- 28508699
TI - Antimicrobial, anticancer, and antioxidant compounds from Premna resinosa growing
in Saudi Arabia.
AB - CONTEXT: Premna resinosa (Hochst.) Schauer (Lamiaceae) is used in many places to
treat bronchitis, respiratory illness and convulsions of the rib cage. OBJECTIVE:
This study evaluates the anticancer, antimicrobial and antioxidant activities of
P. resinosa, and isolates some responsible constituents. MATERIALS AND METHODS:
The methanol extract of P. resinosa aerial parts and its fractions (n-hexane,
dichloromethane, ethyl acetate and n-butanol) were tested. Antimicrobial activity
was tested using microdilution method against three Gram-positive and four Gram
negative bacteria. The tested concentrations ranged from 4000 to 7.8 MUg/mL and
MIC values were determined after 24 h incubation. Anticancer activity was
evaluated against three human cancer cell lines (Daoy, HepG2 and SK-MEL28) using
MTT assay. Antioxidant activity was investigated by DPPH scavenging method and
beta-carotene-linoleic acid assay. RESULTS: The greatest antimicrobial activity
was exhibited by n-hexane fraction (MIC 10 MUg/mL) against Staphylococcus aureus,
Enterococcus faecalis, and Shigella flexneri. The n-hexane fraction induced the
greatest cytotoxic activity against Daoy, HepG2, and SK-MEL28 cell lines with
IC50 values of 9.0, 8.5 and 13.2, respectively. Moreover, the dichloromethane and
ethyl acetate fractions showed the highest antioxidant potential. A bioassay
guided fractionation led to the isolation and characterization of seven compounds
for the first time, namely, quercetin (1), 3-methoxy quercetin (2), kaempferol
(3), 3-methoxy kaempferol (4), myricetin 3,7,3'-trimethyl ether (5), lupeol (6),
and stigmasterol (7). CONCLUSION: Our results indicate that P. resinosa is a
source for antimicrobial and cytotoxic compounds. However, further work is
required to isolate other active principles and to determine the mechanism of
action.
PMID- 28508702
TI - Cluster Analysis in Nursing Research: An Introduction, Historical Perspective,
and Future Directions.
AB - The use of cluster analysis in the nursing literature is limited to the creation
of classifications of homogeneous groups and the discovery of new relationships.
As such, it is important to provide clarity regarding its use and potential. The
purpose of this article is to provide an introduction to distance-based,
partitioning-based, and model-based cluster analysis methods commonly utilized in
the nursing literature, provide a brief historical overview on the use of cluster
analysis in nursing literature, and provide suggestions for future research. An
electronic search included three bibliographic databases, PubMed, CINAHL and Web
of Science. Key terms were cluster analysis and nursing. The use of cluster
analysis in the nursing literature is increasing and expanding. The increased use
of cluster analysis in the nursing literature is positioning this statistical
method to result in insights that have the potential to change clinical practice.
PMID- 28508703
TI - Increased risk of arterial thromboembolic events with combination
lenalidomide/dexamethasone therapy for multiple myeloma.
AB - INTRODUCTION: Cancer associated thrombosis is a leading cause of morbidity and
mortality. Research and guidelines have focused on venous thromboembolic events
(VTE). Within the past decade, combination lenalidomide and dexamethasone has
become a standard of therapy for multiple myeloma and is now widely used. In
these patients, the risk of arterial thromboembolic events (ATE) has not been
addressed to the same extent as VTE. Areas discussed: Presented is a targeted
review of published data on ATE in MM patients on combination
lenalidomide/dexamethasone therapy. Incidence, clinical presentations, prognosis,
mechanisms and thromboprophylaxis are discussed. A framework for approaching
ATE/VTE in these patients is suggested. Expert commentary: There is an increased
incidence of ATE in this population, primarily cerebrovascular and cardiovascular
events. ATE is associated with poorer prognosis and its prevention must be an
important goal of management. It is suggested that on initiating treatment, a
combined VTE/ATE risk assessment should be performed and thromboprophylaxis
initiated for a minimum of 6 months. As newer immunomodulatory therapies are
developed, thromboembolic risk must be assessed early on. Further studies are
needed to determine the optimal strategy to reducing both VTE and ATE in this
population.
PMID- 28508704
TI - Differential expression of genes related to glucose metabolism in domesticated
pigs and wild boar.
AB - Glucose metabolism is a basic biological process that shows substantial variation
within and between species. Using pig as a model organism, we investigated
differences in glucose metabolic genes in seven tissues from domesticated pigs
(Rongchang pig and Tibetan pig, meanwhile, the Tibetan pig just as a special case
of the domesticated pig under plateau condition) and wild boar. We found large
differences in the expression of genes involved in multiple aspects of glucose
metabolism, including genes associated with glucose transport, gluconeogenesis,
and glycolysis. In addition, we identified microRNAs (miRNAs) that may be
involved in the divergence of glucose metabolism in pig. A combined analysis of
mRNA and miRNA expression indicated that some miRNA:mRNA pairs showed ab facto
function in it. Our results provide a valuable resource for further determination
of miRNA regulatory roles in pig glucose metabolism and reveal the divergence of
glucose metabolism in pigs under domestication.
PMID- 28508705
TI - Physical demands of game-based training drills in women's team handball.
AB - Game-based training drills are popular in team sports. This study compared two
game-based training conditions and official matches in team handball. Thirty-one
women players wore inertial measurement units in five training sessions and five
official matches. In training, 3vs3 and 6vs6 game-based training conditions were
performed with a 5-min duration. PlayerLoadTM and high-intensity events (HIEs;
>2.5 m . s-1) were extracted from the raw data. Data were analysed using
magnitude-based inferences and reported with effect sizes (ESs). PlayerLoadTM .
min-1 from all positions combined was 11.37 +/- 0.49 (mean +/- 90% confidence
limits) and 9.71 +/- 0.3 for the 3vs3 and 6vs6 conditions, respectively. Backs
(ES: 1.63), wings (ES: 1.91), and pivots (ES: 1.58) had greater PlayerLoadTM in
3vs3 than 6vs6. Substantially greater HIE . min-1 in 3vs3 occurred for all
positions. There was substantially greater PlayerLoadTM . min-1 in 3vs3 and 6vs6
than match play for backs, wings, and pivots. Wings (ES: 1.95), pivots (ES:
0.70), and goalkeeper (ES: 1.13) had substantially greater HIE . min-1 in 3vs3
than match play. This study shows greater PlayerLoadTM and HIE in 3vs3 than 6vs6.
Both game-based training conditions investigated in this study provide an
overload in overall PlayerLoadTM; however, additional exercises might be needed
to overload HIE, especially for backs and pivots.
PMID- 28508706
TI - British Pakistani lesbians existing within the confines of the closet.
AB - This study explores the complex interaction between ethnicity, gender and
[homo]sexuality and how this creates a framework of stigma that compels some
British Pakistani lesbians to remain within the closet. The 'closet' here is a
metaphor that describes the concealment of one's homosexual identity and the
outward 'performance' of heterosexuality. British Pakistani lesbians precariously
inhabit a sociocultural environment that constrains the expression of female
sexuality. Women who oppose and contravene heteronormative values and ideals
unsettle comfortable assumptions of heterosexuality. Being in the closet keeps
lesbians isolated and marginalised from their ethnic and cultural communities.
Drawing on findings from online interviews with seven British Pakistani lesbians,
the study explores what shapes their decision to stay within the closet and how
doing so influences their self-perception. Being in the closet is a source of
considerable conflict, strain and anxiety, which has an impact on the women's
readiness to embrace individual choice, freedom and desire. Findings orientate
the reader toward an understanding of the multiple, interlocking systems of
social relations within which British Pakistani lesbians are marginalised as the
result of their gender, sexuality and ethnic identity.
PMID- 28508708
TI - Erratum.
PMID- 28508707
TI - Maternal union instability and childhood mortality risk in the Global South, 2010
14.
AB - Efforts to improve child survival in lower-income countries typically focus on
fundamental factors such as economic resources and infrastructure provision, even
though research from post-industrial countries confirms that family instability
has important health consequences. We tested the association between maternal
union instability and children's mortality risk in Africa, Latin America and the
Caribbean, and Asia using children's actual experience of mortality (discrete
time probit hazard models) as well as their experience of untreated morbidity
(probit regression). Children of divorced/separated mothers experience
compromised survival chances, but children of mothers who have never been in a
union generally do not. Among children of partnered women, those whose mothers
have experienced prior union transitions have a higher mortality risk. Targeting
children of mothers who have experienced union instability-regardless of current
union status-may augment ongoing efforts to reduce childhood mortality,
especially in Africa and Latin America where union transitions are common.
PMID- 28508709
TI - Characterisation of the biofouling community on a floating wave energy device.
AB - Wave energy devices are novel structures in the marine environment and, as such,
provide a unique habitat for biofouling organisms. In this study, destructive
scrape samples and photoquadrats were used to characterise the temperate
epibenthic community present on prototypes of the Pelamis wave energy converter.
The biofouling observed was extensive and diverse with 115 taxa recorded
including four non-native species. Vertical zonation was identified on the sides
of the device, with an algae-dominated shallow subtidal area and a deeper area
characterised by a high proportion of suspension-feeding invertebrates.
Differences in species composition and biomass were also observed between
devices, along the length of the device and between sampling dates. This research
provides an insight into the variation of biofouling assemblages on a wave energy
device as well as the potential technical and ecological implications associated
with biofouling on marine renewable energy structures.
PMID- 28508710
TI - Transported biofilms and their influence on subsequent macrofouling colonization.
AB - Biofilm organisms such as diatoms are potential regulators of global macrofouling
dispersal because they ubiquitously colonize submerged surfaces, resist
antifouling efforts and frequently alter larval recruitment. Although ships
continually deliver biofilms to foreign ports, it is unclear how transport shapes
biofilm microbial structure and subsequent macrofouling colonization. This study
demonstrates that different ship hull coatings and transport methods change
diatom assemblage composition in transported coastal marine biofilms. Assemblages
carried on the hull experienced significant cell losses and changes in
composition through hydrodynamic stress, whereas those that underwent sheltered
transport, even through freshwater, were largely unaltered. Coatings and their
associated biofilms shaped distinct macrofouling communities and affected
recruitment for one third of all species, while biofilms from different transport
treatments had little effect on macrofouling colonization. These results
demonstrate that transport conditions can shape diatom assemblages in biofilms
carried by ships, but the properties of the underlying coatings are mainly
responsible for subsequent macrofouling. The methods by which organisms colonize
and are transferred by ships have implications for their distribution,
establishment and invasion success.
PMID- 28508711
TI - Surface sensing and stress-signalling in Ulva and fouling diatoms - potential
targets for antifouling: a review.
AB - Understanding the underlying signalling pathways that enable fouling algae to
sense and respond to surfaces is essential in the design of environmentally
friendly coatings. Both the green alga Ulva and diverse diatoms are important
ecologically and economically as they are persistent biofoulers. Ulva spores
exhibit rapid secretion, allowing them to adhere quickly and permanently to a
ship, whilst diatoms secrete an abundance of extracellular polymeric substances
(EPS), which are highly adaptable to different environmental conditions. There is
evidence, now supported by molecular data, for complex calcium and nitric oxide
(NO) signalling pathways in both Ulva and diatoms being involved in surface
sensing and/or adhesion. Moreover, adaptation to stress has profound effects on
the biofouling capability of both types of organism. Targets for future
antifouling coatings based on surface sensing are discussed, with an emphasis on
pursuing NO-releasing coatings as a potentially universal antifouling strategy.
PMID- 28508713
TI - Investigation of the reasons for not using helmet among motorcyclists in Kerman,
Iran.
AB - This study was carried out to investigate reasoning and interpretation of
motorcyclists for not using helmet utilizing qualitative methodology of 'grounded
theory'. The field of the study was Kerman, a cultural-historical city at the
south-east of Iran. Participants were 21 young male motorcyclists. Two sampling
strategies were used: maximum variation and snowball sampling. To collect data,
in-depth, open-ended interviews were conducted. Data analysis yielded seven
categories: fatalism; a barrier to social relationships; peer group pressure and
negative labelling; messing up the appearance; disturbance in hearing and vision;
barrier to normal breathing; and heaviness and superfluity of helmet. Based on
the findings of the current study, it could be concluded that socio-cultural
contexts, motorcyclists' worldview and partly helmet-related problems are of the
main factors which affect motorcycling. Therefore, the studies, policy-makings,
and intervening programmes to control injury and to promote safety among
motorcyclists should be focused on socio-cultural barriers to helmet use in
general and changing the motorcyclists' standpoints toward fatalism in
particular. Helmet-related problems should be considered, too.
PMID- 28508712
TI - Changing Rates of Morbidity and Mortality in Obstructive Sleep Apnea Surgery.
AB - Objective Whereas uvulopalatopharyngoplasty (UPPP) was the standard surgical
procedure for obstructive sleep apnea prior to 2007, multilevel surgery has
become the standard since that time. This study compares morbidity and mortality
rates of the stand-alone UPPP with those of multilevel sleep surgery that
includes UPPP. Methods Patients undergoing UPPP between 2007 and 2014 were
identified in the American College of Surgeons National Surgical Quality
Improvement Program database. UPPP was defined by Current Procedural Terminology
codes 42145 and 42950. Primary outcomes were incidence of morbidity and
mortality. Rates were compared between a control group with UPPP only and a group
with multilevel surgery. Results A total of 2674 cases were analyzed. The
incidence of complications in the UPPP-only group was 1.6% (0.09% fatal); in the
multilevel surgery group, 4.63% (0.19% fatal). The difference in overall and
nonfatal complications is statistically significant ( P < .01); however, values
for fatal complications are too low for comparison. There is a statistically
significant ( P < .01) positive correlation ( R2 = 0.92) between year of
operation and rate of complications, with increased incidence of complications in
more recent years. Discussion Complication rates for multilevel sleep surgery are
higher than those of stand-alone UPPP, and overall complication rates have been
increasing in recent years. As UPPP supplemented with multilevel surgery is now
the standard surgical treatment for most cases of obstructive sleep apnea
hypopnea syndrome, historical complication rates based predominantly on patients
undergoing UPPP only underestimate complication rates of modern sleep surgery.
Implications for Practice It is reasonable to inform patients that multilevel
procedures bring an increased risk of complications, and patient selection should
be guided accordingly.
PMID- 28508714
TI - Recommendations for clinical biomarker specimen preservation and stability
assessments.
AB - With the wide use of biomarkers to enable critical drug-development decisions,
there is a growing concern from scientific community on the need for a
'standardized process' for ensuring biomarker specimen stability and hence, a
strong desire to share best practices on preserving the integrity of biomarker
specimens in clinical trials and the design of studies to evaluate analyte
stability. By leveraging representative industry experience, we have attempted to
provide an overview of critical aspects of biomarker specimen stability commonly
encountered during clinical development, including: planning of clinical sample
collection procedures, clinical site training, selection of sample preservation
buffers, shipping logistics, fit-for-purpose stability assessments in the
analytical laboratory and presentation of case studies covering widely utilized
biomarker specimen types.
PMID- 28508715
TI - Data and Reporting Quality in Tympanoplasty and Ossiculoplasty Studies.
AB - Objective The objective of our study was to check the documentation of hearing
outcome parameters and influencing factors (surgical, pathological, and
methodological) in published literature evaluating hearing outcome after
tympanoplasty. We aimed to assess how effectively the American Academy of
Otolaryngology-Head and Neck Surgery (AAO-HNS) 1995 guidelines were applied.
Study Design Retrospective noncontrolled study. Setting Ear research center.
Subjects and Methods This study was based on a PubMed research, including peer
reviewed English-speaking original studies published from January 2005 to
December 2015. In total, 169 studies were checked for correct description of
study population, surgical methodology, study design, and documentation of the
hearing outcome. In addition, the correct application of AAO-HNS 1995 criteria
was checked. Results Pre- and postoperative air-bone gap were shown as mean +/-
standard deviation in half of all series (52% vs 56%). The recommended frequency
spectrum (0.5-3 kHz) was used in 46%, while a documentation of frequency spectrum
was available in 85%. Whereas a statement on presence of stapes suprastructure
(81%) and initial pathology was usually available, mucosa status (17%) and
aeration (8%) were only shown in few series. Revision cases, staged cases, and
myringoplasty graft material were documented in 46% to 57%. Type and material of
prosthesis were represented in 74% to 82%. None of the publications analyzed
fulfilled all 10 AAO-HNS criteria. In 10%, 7 to 9 criteria were used correctly.
Conclusion A heterogeneous description of surgical and pathological findings and
the application of minimal reporting standards are essential preconditions to
enable comparisons between different studies and to generate meta-analysis.
PMID- 28508716
TI - Neural correlates of individual differences in fixation duration during natural
reading.
AB - Reading requires integration of language and cognitive processes with attention
and eye movement control. Individuals differ in their reading ability, but little
is known about the neurocognitive processes associated with these individual
differences. To investigate this issue, we combined eyetracking and fMRI,
simultaneously recording eye movements and BOLD activity while subjects read text
passages. We found that the variability and skew of fixation duration
distributions across individuals, as assessed by ex-Gaussian analyses, decreased
with increasing neural activity in regions associated with the cortical eye
movement control network (Left FEF, Left IPS, Left IFG, and Right IFG). The
results suggest that individual differences in fixation duration during reading
are related to underlying neurocognitive processes associated with the eye
movement control system and its relationship to language processing. The results
also show that eye movements and fMRI can be combined to investigate the neural
correlates of individual differences in natural reading.
PMID- 28508717
TI - Expanding the Haitian rehabilitation workforce: employment situation and
perceptions of graduates from three rehabilitation technician training programs.
AB - PURPOSE: This article examines the employment situation and perceptions of
graduates from three rehabilitation technician (RT) programs in Haiti. METHODS:
In this mixed method study, 74 of 93 recent graduates completed a questionnaire,
and 20 graduates participated in an in-depth qualitative interview. We analyzed
survey results using descriptive statistics. We used a qualitative description
approach and analyzed the interviews using constant comparative techniques.
RESULTS: Of the 48 survey respondents who had completed their training more than
six months prior to completing the questionnaire, 30 had found work in the
rehabilitation sector. Most of these technicians were working in hospitals in
urban settings and the patient population they treated most frequently were
patients with neurological conditions. Through the interviews, we explored the
participants' motivations for becoming a RT, reflections on the training program,
process of finding work, current employment, and plans for the future. An
analysis of qualitative and quantitative findings provides insights regarding
challenges, including availability of supervision for graduated RTs and the
process of seeking remunerated work. CONCLUSIONS: This study highlights the need
for stakeholders to further engage with issues related to formal recognition of
RT training, expectations for supervision of RTs, concerns for the precariousness
of their employment, and uncertainty about their professional futures.
Implications for Rehabilitation The availability of human resources in the
rehabilitation field in Haiti has increased with the implementation of three RT
training programs over the past 10 years. RTs who found work in the
rehabilitation sector were more likely to work in a hospital setting, in the
province where their training had taken place, to treat a diverse patient
clientele, and to be employed by a non-governmental organization. The study
underlines challenges related to the long-term sustainability of RT training
programs, as well as the employment of their graduates. Further discussion and
research are needed to identify feasible and effective mechanisms to provide
supervision for RTs within the Haitian healthcare system.
PMID- 28508718
TI - Frondoside A induces AIF-associated caspase-independent apoptosis in Burkitt
lymphoma cells.
AB - For patients with refractory or relapsed Burkitt lymphoma (BL), no standard
therapy is available for second-line treatment to date. Nonfunctional caspases
dependent apoptosis pathways, inactivating p53 mutations and pro-survival
autophagy prevent activity of conventional chemotherapy. Thus, new drugs
bypassing these mechanisms of resistance are required. Here, we investigated the
efficacy of the marine natural compound frondoside A (FrA) in eight BL cell
lines. FrA revealed cytotoxic effects in all cell lines tested including the
multiresistant CA46 cells. Remarkably, FrA induced caspases- and p53-independent
apoptosis, which was characterized by decreased expression of antiapoptotic
survivin and Bcl-2, mitochondria targeting (release of cytochrome C, HtrA2/Omi
and the apoptosis-inducing factor (AIF), and altered production of ROS) and
translocation of AIF to the nuclei. In addition, signs of inhibition of pro
survival autophagy were observed. Thus, FrA is a promising candidate for the
treatment of refractory or relapsed BL revealing resistances to standard
therapies.
PMID- 28508719
TI - Kahweol inhibits adipogenesis of 3T3-L1 adipocytes through downregulation of
PPARgamma.
AB - Kahweol, a compound from Coffea arabica, possesses antioxidant, anti
inflammatory, and antitumour properties. However, an anti-adipogenic effect has
not yet been reported. In this study, we have shown that kahweol has an anti
adipogenic effect on 3T3-L1 adipocytes. Kahweol significantly inhibited the
differentiation of intracellular lipid accumulation in 3T3-L1 adipocytes, without
being cytotoxic. It also downregulated the expression of adipogenesis-related
gene, including an adipocytokine, adiponectin. This anti-adipogenic effect stems
from an ability to inhibit key adipogenic regulators, including PPARgamma and
C/EBPalpha. These results demonstrate that kahweol significantly inhibits the
differentiation of 3T3-L1 cells, and suggest that it has potential as a novel
anti-obesity treatment.
PMID- 28508720
TI - Human Kinematics of Cochlear Implant Surgery: An Investigation of Insertion Micro
Motions and Speed Limitations.
AB - Objectives Document human motions associated with cochlear implant electrode
insertion at different speeds and determine the lower limit of continuous
insertion speed by a human. Study Design Observational. Setting Academic medical
center. Subjects and Methods Cochlear implant forceps were coupled to a frame
containing reflective fiducials, which enabled optical tracking of the forceps'
tip position in real time. Otolaryngologists (n = 14) performed mock electrode
insertions at different speeds based on recommendations from the literature:
"fast" (96 mm/min), "stable" (as slow as possible without stopping), and "slow"
(15 mm/min). For each insertion, the following metrics were calculated from the
tracked position data: percentage of time at prescribed speed, percentage of time
the surgeon stopped moving forward, and number of direction reversals (ie, going
from forward to backward motion). Results Fast insertion trials resulted in
better adherence to the prescribed speed (45.4% of the overall time), no motion
interruptions, and no reversals, as compared with slow insertions (18.6% of time
at prescribed speed, 15.7% stopped time, and an average of 18.6 reversals per
trial). These differences were statistically significant for all metrics ( P <
.01). The metrics for the fast and stable insertions were comparable; however,
stable insertions were performed 44% slower on average. The mean stable insertion
speed was 52 +/- 19.3 mm/min. Conclusion Results indicate that continuous
insertion of a cochlear implant electrode at 15 mm/min is not feasible for human
operators. The lower limit of continuous forward insertion is 52 mm/min on
average. Guidelines on manual insertion kinematics should consider this practical
limit of human motion.
PMID- 28508721
TI - Acute renal failure with need for renal replacement therapy as a complication of
zoonotic S. zooepidemicus infection: case report and review of the literature.
AB - Streptococcus zooepidemicus is an animal commensal with the potential of zoonotic
transmission through ingestion of contaminated dairy products, leading to
outbreaks of Post-Streptococcal Glomerulonephritis (PSGN). We report for the
first time acute renal failure with need for renal replacement therapy, as a
complication of S. zooepidemicus bacteremia resulting from direct horse to human
transmission in a young adult. Both clinical disease course and
immunohistochemical staining patterns on renal biopsy had some atypical features
of PSGN suggesting persistent activation of the alternative complement pathway
but no known complement factor dysregulations could be identified.
PMID- 28508722
TI - A Natural History of the Drag Queen Phenomenon.
AB - The drag queen cultural phenomenon has been described at length. However, the
depiction of outlandish and hyperbolic womanhood and taunting and formidable
behavior at the core of drag queens' public persona has still to be fully
accounted for. We argue that these aspects of the drag queen's public appearance
could best be understood in a signaling framework. Publicly donning extravagant
woman's costumes attracts harassment and brings financial, mating, and
opportunity costs, generating the conditions for the transmission of honest
signals. By successfully withstanding those odds, drag queen impersonators signal
strategic qualities to members of the gay community. Data collected among gay and
straight participants support a costly signaling reading of the drag queen
cultural phenomenon. Participants generally agree that successful drag queens
typically incur costs, while gaining specific social benefits.
PMID- 28508723
TI - Drinking High Amounts of Alcohol as a Short-Term Mating Strategy: The Impact of
Short-Term Mating Motivations on Young Adults' Drinking Behavior.
AB - Previous research indicates that drinking large quantities of alcohol could
function as a short-term mating strategy for young adults in mating situations.
However, no study investigated whether this is actually the case. Therefore, in
this article, the link between short-term mating motivations and drinking high
amounts of alcohol is tested. First, a survey study ( N = 345) confirmed that
young adults who engage in binge drinking are more short-term oriented in their
mating strategy than young adults who never engage in binge drinking. Also, the
more short-term-oriented young adults were in their mating strategy, the more
often binge drinking behavior was conducted. In addition, an experimental study (
N = 229) empirically verified that short-term mating motivations increase young
adults' drinking behavior, more so than long-term mating motivations. Results of
the experiment clearly showed that young men and young women are triggered to
drink more alcoholic beverages in a short-term mating situation compared to a
long-term mating situation. Furthermore, the mating situation also affected young
adults' perception of drinking behavior. Young adults in a short-term mating
context perceived a higher amount of alcoholic beverages as heavy drinking
compared to peers in a long-term mating context. These findings confirm that a
high alcohol consumption functions as a short-term mating strategy for both young
men and young women. Insights gained from this article might be of interest to
institutions aimed at targeting youth alcohol (ab)use.
PMID- 28508724
TI - The impact of simulated motion blur on lesion detection performance in full-field
digital mammography.
AB - OBJECTIVE: Motion blur is a known phenomenon in full-field digital mammography,
but the impact on lesion detection is unknown. This is the first study to
investigate detection performance with varying magnitudes of simulated motion
blur. METHODS: 7 observers (15 +/- 5 years' reporting experience) evaluated 248
cases (62 containing malignant masses, 62 containing malignant
microcalcifications and 124 normal cases) for 3 conditions: no blurring (0 mm)
and 2 magnitudes of simulated blurring (0.7 and 1.5 mm). Abnormal cases were
biopsy proven. Mathematical simulation was used to provide a pixel shift in order
to simulate motion blur. A free-response observer study was conducted to compare
lesion detection performance for the three conditions. The equally weighted
jackknife alternative free-response receiver operating characteristic was used as
the figure of merit. Test alpha was set at 0.05 to control probability of Type I
error. RESULTS: The equally weighted jackknife alternative free-response receiver
operating characteristic analysis found a statistically significant difference in
lesion detection performance for both masses [F(2,22) = 6.01, p = 0.0084] and
microcalcifications [F(2,49) = 23.14, p < 0.0001]. The figures of merit reduced
as the magnitude of simulated blurring increased. Statistical differences were
found between some of the pairs investigated for the detection of masses (0.0 vs
0.7 and 0.0 vs 1.5 mm) and all pairs for microcalcifications (0.0 vs 0.7, 0.0 vs
1.5 and 0.7 vs 1.5 mm). No difference was detected between 0.7 and 1.5 mm for
masses. CONCLUSION: The mathematical simulation of motion blur caused a
statistically significant reduction in lesion detection performance. These false
negative decisions could have implications for clinical practice. Advances in
knowledge: This research demonstrates for the first time that motion blur has a
negative and statistically significant impact on lesion detection performance in
digital mammography.
PMID- 28508725
TI - Evaluating change in virtual reality adoption for brain injury rehabilitation
following knowledge translation.
AB - PURPOSE: To evaluate the impact of knowledge translation (KT) on factors
influencing virtual reality (VR) adoption and to identify support needs of
therapists. HYPOTHESES: Intervention will be associated with improvements in
therapists' perceived ease of use and self-efficacy, and an associated increase
in intentions to use VR. METHOD: Single group mixed-methods pre-test-post-test
evaluation of convenience sample of physical, occupational and rehabilitation
therapists (n=37) from two brain injury rehabilitation centres. ADOPT-VR
administered pre/post KT intervention, consisting of interactive education,
clinical manual, technical and clinical support. RESULTS: Increases in perceived
ease of use (p=0.000) and self-efficacy (p=0.001), but not behavioural intention
to use VR (p=0.158) were found following KT, along with decreases in the
frequency of perceived barriers. Post-test changes in the frequency and nature of
perceived facilitators and barriers were evident, with increased emphasis on peer
influence, organisational-level supports and client factors. Additional support
needs were related to clinical reasoning, treatment programme development,
technology selection and troubleshooting. CONCLUSIONS: KT strategies hold
potential for targeting therapists' perceptions of low self-efficacy and ease of
use of this technology. Changes in perceived barriers, facilitators and support
needs at post-test demonstrated support for repeated evaluation and multi-phased
training initiatives to address therapists' needs over time. Implications for
Rehabilitation Therapists' learning and support needs in integrating virtual
reality extend beyond technical proficiency to include clinical decision-making
and application competencies spanning the entire rehabilitation process. Phased,
multi-faceted strategies may be valuable in addressing therapists' changing needs
as they progress from novice to experienced virtual reality users. The ADOPT-VR
is a sensitive measure to re-evaluate the personal, social, environmental,
technology-specific and system-level factors influencing virtual reality adoption
over time.
PMID- 28508726
TI - Does the Timing of Middle Turbinate Resection Influence Quality-of-Life Outcomes
for Patients with Chronic Rhinosinusitis?
AB - Objective To evaluate the impact of bilateral middle turbinate resection (BMTR)
on patient-reported quality of life following primary and revision endoscopic
sinus surgery (ESS) for chronic rhinosinusitis (CRS). Study Design Prospective
cohort study. Setting Tertiary care center. Subjects and Methods Patients with
CRS who were recruited from 11 otolaryngologic practices completed the Sino-Nasal
Outcome Test-22, Chronic Sinusitis Survey, and EuroQol 5-Dimension questionnaires
at baseline, as well as 3 and 12 months after ESS. In the primary ESS cohort (n =
406), patients who underwent BMTR (n = 78) at the time of surgery were compared
with patients (n = 328) whose middle turbinates were preserved. In the revision
ESS cohort (n = 363), a similar comparison was made between patients who did (n =
64) and did not (n = 299) undergo BMTR. Results Sino-Nasal Outcome Test-22,
Chronic Sinusitis Survey, and EuroQol 5-Dimension scores showed similar
improvements for both the turbinate resection and preservation cohorts at 3
months ( P < .001) and 12 months ( P < .001) after surgery. For patients who
underwent revision surgery, the performance of BMTR resulted in greater
improvement in Chronic Sinusitis Survey scores at 1 year as compared with the
turbinate preservation group (change from baseline: 28.1 vs 20.7, respectively; P
= .026). History of tobacco use and the presence of nasal polyps did not affect
clinical outcomes at any time point. Conclusion Patients who underwent BMTR
during primary and revision sinus surgery reported similar benefits in quality-of
life outcomes 1 year after surgery. In select patients undergoing revision sinus
surgery, the performance of BMTR results in improved disease-specific quality of
life.
PMID- 28508729
TI - Disciplinary action against solicitors and the role of the Solicitors
Disciplinary Tribunal.
PMID- 28508727
TI - The role of Wnt signaling in hematopoietic stem cell development.
PMID- 28508728
TI - High frequency of identical clonal immunoglobulin DNA in pre-treatment tumor and
plasma from untreated patients with HIV-associated lymphoma: prospective
multicenter trial of the AIDS malignancies consortium (AMC 064).
AB - Patients with HIV are at increased risk for developing B-cell lymphomas likely
due in part to chronic antigen stimulation leading to clonal immunoglobulin (Ig)
gene rearrangements. Next-generation sequencing (NGS)-based identification of
circulating Ig clonotypes has not been well-characterized in HIV-related
lymphomas. The AIDS Malignancies Consortium (AMC) enrolled 51 untreated patients
with HIV-related B-cell lymphomas and analyzed paired tumor/plasma specimens for
Ig clonotypes using an NGS approach (AMC064, NCT00981097). Lymphoma-specific
clonotypes (>5% frequency) were identified in 83% (33/40) of tumor specimens.
Results from paired tumor/plasma specimens showed identical circulating
clonotypes in the plasma from 97% (32/33) of patients. High International
Prognostic Index (IPI) scores of 3-4 among patients with B-cell lymphoma
correlated with higher lymphoma molecules/million diploid genomes in the plasma
compared with lower IPI scores of 0-2, median 77335 vs. 6876, p = .005. Further
studies are merited to determine whether plasma clonal Ig DNA is prognostic in
HIV-related lymphomas.
PMID- 28508731
TI - Submitting medico-legal intra-partum CTG (I-P CTG) monitoring to the Bolam and
Bolitho principles.
AB - The article analyses some of the seeming weaknesses of the Bolam and Bolitho
tests as applied to electronic foetal monitoring in labour, in the form of intra
partum CTG monitoring. Homing on to such aspects as confirmation of foetal
hypoxia/acidosis, it evaluates the Bolam and Bolitho tests in the context of
evidence-based medicine versus traditionally held views, which still hold their
own in medical jurisprudence. Case law examples are quoted to illustrate various
points. The discussion is of practical relevance both to the individual
obstetrician as well as to national budgetary implications, bearing in mind,
that, for example, in 2011, 'birth asphyxia' comprised 50% of the UK NHS
litigation costs, and in the 2000-2010 decade, the same NHS forked out L3.1
billion for maternity medico-legal claims (the highest of any speciality), mostly
involving cerebral palsy and CTG misinterpretation. The article concludes with
suggestions to help level the potential extant equivocity between legal principle
and medical practice. It also looks at the ruling in Montgomery v Lanarkshire
Health Board, UK Supreme Court, and its challenge to Bolam. The implications pose
a serious and overdue challenge to a test, born in 1957 and lacking the necessary
qualities to serve many 21st century medical quandaries, including the ones
raised here.
PMID- 28508732
TI - Editorial.
PMID- 28508730
TI - A rare fatality due to calcified stylohyoid ligament (Eagle syndrome).
AB - The elongation or calcification of the stylohyoid ligament that leads to pressure
symptoms, or entrapment of nearby glossopharyngeal nerve or carotid artery, is
known as Eagle syndrome. A PubMed search leads to finding of rare fatality among
the 49 reported cases. In the present case, the deceased was a 40-year-old male
who choked on his food. We hypothesise that the impaction of food in the upper
respiratory tract, as well as the inability to intubate the person, were both the
result of the calcified stylohyoid ligament.
PMID- 28508733
TI - Synthesis of aurachins B and H.
AB - The synthesis of aurachin B, an antibiotic that features a C3-oxygen-substituted
quinoline N-oxide nucleus bearing a farnesyl side chain at C4, was accomplished
in 60% overall yield from o-nitrotoluene by a concise five-step sequence. An
enantioselective synthesis of aurachin H was also achieved for the first time in
only two steps from an optically active epoxy iodide.
PMID- 28508734
TI - The role of cue utilisation in reducing the workload in a train control task.
AB - Skilled performance has been characterised, in part, by the capacity to
accurately identify and respond to patterns as cues in the environment. The
outcome is a reduction in cognitive load and a greater residual capacity to
undertake concurrent tasks. The present study was designed to examine the
relationship between cue utilisation and temporal pattern recognition in the
context of a simulated, rail control task. Sixty-one university students
undertook an assessment of cue utilisation and engaged in a rail control
simulation. The appearance and movement of trains followed a consistent but
implicit (undisclosed) pattern. Throughout the second half of the rail task, a
secondary task was included. The results indicated that participants with
relatively higher cue utilisation were more likely to identify the implicit
pattern of rail movements, were more accurate and responded more rapidly under
increased workload conditions. The results suggest that a propensity to identify
patterns as cues may provide an opportunity to reduce cognitive demands, thereby
facilitating performance in a novel task. Implications for selection and system
design are discussed. Practitioner Summary: This study was designed to explain
differences in the way in which people learn, particularly when tasks involve
recurring patterns. Using simulated rail control, the results indicated that
participants who display behaviour that is indicative of the utilisation of cues
also recognise patterns in the movement of simulated trains. This enables them to
manage trains more effectively, even while undertaking other tasks.
PMID- 28508735
TI - Sleep problems in breast cancer survivors 1-10 years posttreatment.
AB - : ABSTRACTObjective:Sleep can affect quality of life (QoL) during cancer
survivorship, and symptoms related to poor sleep can be exacerbated. We examined
the prevalence, severity, and nature of subjective sleep complaints in women
surviving stage I-III breast cancer who were 1-10 years posttreatment. We also
examined the demographic, medical, physical, and psychosocial correlates of poor
sleep in these women in order to identify the subgroups that may be most in need
of intervention. METHOD: A total of 200 patients at a comprehensive cancer center
who were 1-10 years posttreatment for primary stage I-III breast cancer with no
evidence of disease at the time of enrollment completed a battery of
questionnaires on demographics, sleep, physical symptoms, mood, cancer-specific
fears, and QoL. RESULTS: The women had a mean age of 57 years (SD = 10.0), with a
mean of 63.3 months (SD = 28.8) of post-cancer treatment. Some 38% of these
patients were identified as having poor-quality sleep. Women with poor sleep took
longer to fall asleep, had more awakenings, and acquired 2 hours less sleep per
night than those with good sleep. They also had a lower QoL, greater severity of
pain, more concerns about health and recurrence, and increased vasomotor symptoms
(p < 0.05). Daytime sleepiness and depression were found to be not significantly
correlated with sleep quality. SIGNIFICANCE OF RESULTS: Many breast cancer
survivors had severe subjective insomnia, and several breast cancer survivor
subgroups were identified as having members who might be most in need of sleep
improvement interventions. Addressing physical symptoms (e.g., vasomotor symptoms
and pain) and providing education about the behavioral, social, environmental,
and medical factors that affect sleep could result in substantial improvement in
the life course of breast cancer survivors.
PMID- 28508736
TI - Out of harm's way: Secure versus insecure-disorganized attachment predicts less
adolescent risk taking related to childhood poverty.
AB - Although some risk taking in adolescence is normative, evidence suggests that
adolescents raised in conditions of socioeconomic disadvantage are
disproportionately burdened with risk taking and its negative consequences. Using
longitudinal data from the NICHD Study of Early Child Care and Youth Development,
we investigated quality of the early caregiving environment as a potential
prospective buffer against the long-term association between childhood poverty
and adolescent risk taking. Multicategorical moderation model results indicated
that if raised in poverty across age 1-54 months (average family income to needs
ratio <= 1.02), relative to affluence (income to needs ratio >= 6.16),
adolescents with histories of secure attachment to caregivers exhibited two times
the number of risk behaviors at age 15, whereas adolescents with insecure
disorganized histories exhibited nearly five times the number of risk behaviors.
Both early family economic hardship and history of insecure-disorganized
attachment remained significant predictors of increased adolescent risk taking,
alongside the interactive effect. Probing the interaction's region of
significance revealed that history of secure (vs. insecure-disorganized)
attachment is associated with protective reductions in risk taking below a family
income to needs ratio of 2.24, or about 220% poverty level. Findings support a
diathesis-stress model in which children with secure attachment histories are
less deleteriously impacted by early socioeconomic adversity than their insecure
disorganized peers.
PMID- 28508737
TI - The future for long chain n-3 PUFA in the prevention of coronary heart disease:
do we need to target non-fish-eaters?
AB - Dietary guidelines in many countries include a recommendation to consume oily
fish, mainly on the basis of evidence from prospective cohort studies that fish
consumption is cardioprotective. However, average intakes are very low in a large
proportion of the UK population. Some groups, such as vegans and vegetarians,
purposely omit fish (along with meat) from their diet resulting in zero or trace
intakes of long chain (LC) n-3 PUFA. Although the efficacy of dietary fish oil
supplementation in the prevention of CVD has been questioned in recent years, the
balance of evidence indicates that LC n-3 PUFA exert systemic pleiotropic effects
through their influence on gene expression, cell signalling, membrane fluidity
and by conversion to specialised proresolving mediators; autacoid lipid mediators
that resolve inflammatory events. The long-term impact of reduced tissue LC n-3
PUFA content on cardiovascular health is surprisingly poorly understood,
particularly with regard to how low proportions of LC n-3 PUFA in cell membranes
may affect cardiac electrophysiology and chronic inflammation. Randomised
controlled trials investigating effects of supplementation on prevention of CHD
in populations with low basal LC n-3 PUFA tissue status are lacking, and so the
clinical benefits of supplementing non-fish-eating groups with vegetarian sources
of LC n-3 PUFA remain to be determined. Refocusing dietary LC n-3 PUFA
intervention studies towards those individuals with a low LC n-3 PUFA tissue
status may go some way towards reconciling results from randomised controlled
trials with the epidemiological evidence.
PMID- 28508738
TI - Social-ecological predictors of externalizing behavior trajectories in at-risk
youth.
AB - Extant research consistently links youth externalizing problems and later
maladaptive outcomes, and these behaviors are particularly detrimental given
their relative stability across development. Although an array of risk and
protective factors for externalizing problems have been identified, few studies
have examined factors reflecting the multiple social-ecological levels that
influence child development and used them to predict longitudinal trajectories of
externalizing problems. The current study examined externalizing behavior
trajectories in a sample of 1,094 at-risk youth (539 boys, 555 girls) from the
Longitudinal Studies in Child Abuse and Neglect multisite longitudinal study of
child maltreatment. Normed Child Behavior Checklist externalizing scores were
used to estimate group trajectories via growth-based trajectory modeling at ages
10, 12, 14, and 16 using the SAS PROC TRAJ procedure. Model fit was assessed
using the Bayes information criterion and the Akaike information criterion
statistics. Analyses revealed optimal fit for five distinct behavioral
trajectories: low stable, mid-increasing, mid-decreasing, medium high, and high
stable. Multinomial logistic regressions revealed that a combination of risk and
protective factors at individual, family, school, and neighborhood levels
contribute to distinct trajectories of externalizing problems over time.
Predictors of low and decreasing trajectories can inform interventions aimed at
addressing externalizing problems among high-risk adolescents.
PMID- 28508739
TI - The effects of supportive care interventions on depressive symptoms among
patients with lung cancer: A metaanalysis of randomized controlled studies.
AB - OBJECTIVE: Our aim was to examine the effect of supportive care interventions on
depressive symptoms in patients with lung cancer. METHOD: We searched the
databases of the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid
EMBASE, PubMed, and the Chinese Electronic Periodical Services (CEPS) from their
inception until September of 2015. We included randomized controlled trial
studies that compared standard care with supportive care interventions. The
standardized mean difference (SMD) (Cohen's d) was calculated to estimate the
effect of interventions. Subgroup analysis was conducted to identify possible
sources of heterogeneity. RESULTS: A total of 1,472 patients with lung cancer
were identified. Compared with standard care, the overall effects of all
supportive care interventions significantly reduced depressive symptoms (SMD =
0.74, CI 95% = -1.07 to -0.41), and the effects could be maintained at weeks 4,
8, and 12 of follow-up. Three types of supportive care interventions were
identified: psychotherapy combined with psychoeducation, psychoeducation alone,
and an exercise program. Both psychotherapy combined with psychoeducation and
exercise significantly improved depressive symptoms, while psychoeducation alone
did not yield significant effects. The moderating effects indicated that greater
improvements in depressive symptoms were found in lung cancer patients with a
severe level of depressive symptoms at baseline. SIGNIFICANCE OF RESULTS:
Personalized supportive care interventions can be developed based on the main
causes of depressive symptoms. Psychotherapy combined with psychoeducation can
target the causes of depressive symptoms, including both physical distress and
psychological trauma due to lung cancer, while exercise programs can effectively
improve depressive symptoms for lung cancer patients with impaired respiratory
function.
PMID- 28508740
TI - CAEP 2016 Academic Symposium: A Writer's Guide to Key Steps in Producing Quality
Medical Education Scholarship.
AB - A key skill for successful clinician educators is the effective dissemination of
scholarly innovations and research. Although there are many ways to disseminate
scholarship, the most accepted and rewarded form of educational scholarship is
publication in peer-reviewed journals. This paper provides direction for
emergency medicine (EM) educators interested in publishing their scholarship via
traditional peer-reviewed avenues. It builds upon four literature reviews that
aggregated recommendations for writing and publishing high-quality quantitative
and qualitative research, innovations, and reviews. Based on the findings from
these literature reviews, the recommendations were prioritized for importance and
relevance to novice clinician educators by a broad community of medical
educators. The top items from the expert vetting process were presented to the
2016 Canadian Association of Emergency Physicians (CAEP) Academic Symposium
Consensus Conference on Education Scholarship. This community of EM educators
identified the highest yield recommendations for junior medical education
scholars. This manuscript elaborates upon the top recommendations identified
through this consensus-building process.
PMID- 28508741
TI - CAEP 2016 Academic Symposium on Education Scholarship: Training our Future
Clinician Educators in Emergency Medicine.
AB - OBJECTIVE: To develop consensus recommendations for training future clinician
educators (CEs) in emergency medicine (EM). METHODS: A panel of EM education
leaders was assembled from across Canada and met regularly by teleconference over
the course of 1 year. Recommendations for CE training were drafted based on the
panel's experience, a literature review, and a survey of current and past EM
education leaders in Canada. Feedback was sought from attendees at the Canadian
Association of Emergency Physicians (CAEP) annual academic symposium.
Recommendations were distributed to the society's Academic Section for further
feedback and updated by a consensus of the expert panel. RESULTS: Recommendations
were categorized for one of three audiences: 1) Future CEs; 2) Academic
departments and divisions (AD&D) that support training to fulfill their education
leadership goals; and 3) The CAEP Academic Section. Advanced medical education
training is recommended for any emergency physician or resident who pursues an
education leadership role. Individuals should seek out mentorship in making
decisions about career opportunities and training options. AD&D should regularly
perform a needs assessment of their future CE needs and identify and encourage
potential individuals who fulfill education leadership roles. AD&D should develop
training opportunities at their institution, provide support to complete this
training, and advocate for the recognition of education scholarship in their
institutional promotions process. The CAEP Academic Section should support
mentorship of future CEs on a national scale. CONCLUSION: These recommendations
serve as a framework for training and supporting the next generation of Canadian
EM medical educators.
PMID- 28508742
TI - CAEP 2016 Academic Symposium: How to have an impact as an emergency medicine
educator and scholar.
AB - BACKGROUND: In a time of major medical education transformation, emergency
medicine (EM) needs to nurture education scholars who will influence EM education
practice. However, the essential ingredients to ensure a career with impact in EM
education are not clear. OBJECTIVE: To describe how to prepare EM educators for a
high-impact career. METHODS: The Canadian Association of Emergency Physicians
(CAEP) Academic Section commissioned an "Education Impact" working group (IWG) to
guide the creation of consensus recommendations from the EM community. EM
educators from across Canada were initially recruited from the networks of the
IWG members, and additional educators were recruited via snowball sampling. "High
impact educators" were nominated by this network. The high impact educators were
then interviewed using a structured question guide. These interviews were
transcribed and coded for themes using qualitative methods. The process continued
until no new themes were identified. Proposed themes and recommendations were
presented to the EM community at the CAEP 2016 Academic Symposium. Feedback was
then incorporated into a final set of recommendations. RESULTS: Fifty-five (71%)
of 77 of identified Canadian EM educators participated, and 170 names of high
impact educators were submitted and ranked by frequency. The IWG achieved
sufficiency of themes after nine interviews. Five recommendations were made: 1)
EM educators can pursue a high impact career by leveraging either traditional or
innovative career pathways; 2) EM educators starting their education careers
should have multiple senior mentors; 3) Early-career EM educators should immerse
themselves in their area of interest and cultivate a community of practice, not
limited to EM; 4) Every academic EM department and EM teaching site should have
access to an EM educator with protected time and recognition for their EM
education scholarship; and 5) Educators at all stages should continuously compile
an impact portfolio. CONCLUSIONS: We describe a unique set of recommendations to
develop educators who will influence EM, derived from a consensus from the EM
community. EM leaders, educators, and aspiring educational scholars should
consider how to implement this guide towards enhancing our specialty's
educational mission.
PMID- 28508744
TI - Overexpression of Human Papillomavirus Type 16 Oncoproteins Enhances Epithelial
Mesenchymal Transition via STAT3 Signaling Pathway in Non-Small Cell Lung Cancer
Cells.
AB - The human papillomavirus (HPV) infection may be associated with the development
and progression of non-small cell lung cancer (NSCLC). However, the role of HPV
16 oncoproteins in the development and progression of NSCLC is not completely
clear. Epithelial-mesenchymal transition (EMT), a crucial step for invasion and
metastasis, plays a key role in the development and progression of NSCLC. Here we
explored the effect of HPV-16 oncoproteins on EMT and the underlying mechanisms.
NSCLC cell lines, A549 and NCI-H460, were transiently transfected with the EGFP
N1-HPV-16 E6 or E7 plasmid. Real-time PCR and Western blot analysis were
performed to analyze the expression of EMT markers. A protein microarray was used
to screen the involved signaling pathway. Our results showed that overexpression
of HPV-16 E6 and E7 oncoproteins in NSCLC cells significantly promoted EMT-like
morphologic changes, downregulated the mRNA and protein levels of EMT epithelial
markers (E-cadherin and ZO-1), and upregulated the mRNA and protein levels of EMT
mesenchymal markers (N-cadherin and vimentin) and transcription factors (ZEB-1
and Snail-1). Furthermore, the HPV-16 E6 oncoprotein promoted STAT3 activation.
Moreover, WP1066, a specific signal transducer and activator of transcription 3
(STAT3) inhibitor, reversed the effect of HPV-16 E6 on the expression of ZO-1,
vimentin, and ZEB-1 in transfected NSCLC cells. Taken together, our results
suggest that overexpression of HPV-16 E6 and E7 oncoproteins enhances EMT, and
the STAT3 signaling pathway may be involved in HPV-16 E6-induced EMT in NSCLC
cells.
PMID- 28508745
TI - Natural Leishmania (Viannia) infections of phlebotomines (Diptera: Psychodidae)
indicate classical and alternative transmission cycles of American cutaneous
leishmaniasis in the Guiana Shield, Brazil.
AB - From 1996 to 1999 multi-trapping methods (Center of Diseases Control, CDC) light
traps, light-baited Shannon traps, and aspiration on tree bases) were used to
study the phlebotomine fauna of the "Serra do Navio" region of the Brazilian
State of Amapa, which is part of the Guiana Shield. Fifty-three species were
identified among 8,685 captured individuals. The following species, associated
with the transmission of American cutaneous leishmaniasis in Amazonian Brazil,
were captured: Nyssomyia umbratilis (3,388), Psychodopygus squamiventris
maripaensis (995), Ny. anduzei (550), Trichophoromyia ubiquitalis (400), Ny.
whitmani (291), Ps. paraensis (116), and Bichromomyia flaviscutellata (50).
Flagellate infections were detected in 45 flies. Of the 19 parasites isolated in
vitro, 15 were Leishmania (Viannia) guyanensis (13 in Ny. umbratilis, 1 in Ny.
whitmani, 1 in Ny. anduzei) and three were L. (V.) naiffi (2 in Ps. s.
maripaensis, 1 in Ny. anduzei). The results indicate the participation of three
phlebotomine species in the transmission of L. (V.) guyanensis and two species in
that of L. (V.) naiffi, and show that the same phlebotomine species is involved
in the transmission of different Leishmania (Viannia) species in the
Guianan/Amazon region. A review of the literature together with the results of
the present study, and other published and unpublished results, indicate that
eight phlebotomine species potentially participate in the transmission of
Leishmania (Viannia) naiffi in Amazonia.
PMID- 28508746
TI - Ciliomotor circuitry underlying whole-body coordination of ciliary activity in
the Platynereis larva.
AB - Ciliated surfaces harbouring synchronously beating cilia can generate fluid flow
or drive locomotion. In ciliary swimmers, ciliary beating, arrests, and changes
in beat frequency are often coordinated across extended or discontinuous
surfaces. To understand how such coordination is achieved, we studied the
ciliated larvae of Platynereis dumerilii, a marine annelid. Platynereis larvae
have segmental multiciliated cells that regularly display spontaneous coordinated
ciliary arrests. We used whole-body connectomics, activity imaging, transgenesis,
and neuron ablation to characterize the ciliomotor circuitry. We identified
cholinergic, serotonergic, and catecholaminergic ciliomotor neurons. The
synchronous rhythmic activation of cholinergic cells drives the coordinated
arrests of all cilia. The serotonergic cells are active when cilia are beating.
Serotonin inhibits the cholinergic rhythm, and increases ciliary beat frequency.
Based on their connectivity and alternating activity, the catecholaminergic cells
may generate the rhythm. The ciliomotor circuitry thus constitutes a stop-and-go
pacemaker system for the whole-body coordination of ciliary locomotion.
PMID- 28508747
TI - Voltage-gated Na+ currents in human dorsal root ganglion neurons.
AB - Available evidence indicates voltage-gated Na+ channels (VGSCs) in peripheral
sensory neurons are essential for the pain and hypersensitivity associated with
tissue injury. However, our understanding of the biophysical and pharmacological
properties of the channels in sensory neurons is largely based on the study of
heterologous systems or rodent tissue, despite evidence that both expression
systems and species differences influence these properties. Therefore, we sought
to determine the extent to which the biophysical and pharmacological properties
of VGSCs were comparable in rat and human sensory neurons. Whole cell patch clamp
techniques were used to study Na+ currents in acutely dissociated neurons from
human and rat. Our results indicate that while the two major current types,
generally referred to as tetrodotoxin (TTX)-sensitive and TTX-resistant were
qualitatively similar in neurons from rats and humans, there were several
differences that have important implications for drug development as well as our
understanding of pain mechanisms.
PMID- 28508749
TI - Diagnostic properties of provocation tests for cold, heat, and delayed-pressure
urticaria.
PMID- 28508750
TI - A case of basal cell carcinoma with a neighbouring melanocytic nevus: dermoscopic
features.
PMID- 28508751
TI - The value of teledermatology using a mobile app compared to conventional
dermatology.
PMID- 28508752
TI - Nail toxicities induced by liposomal doxorubicin: a retrospective case series.
PMID- 28508748
TI - Macrophages are necessary for epimorphic regeneration in African spiny mice.
AB - How the immune system affects tissue regeneration is not well understood. In this
study, we used an emerging mammalian model of epimorphic regeneration, the
African spiny mouse, to examine cell-based inflammation and tested the hypothesis
that macrophages are necessary for regeneration. By directly comparing
inflammatory cell activation in a 4 mm ear injury during regeneration (Acomys
cahirinus) and scarring (Mus musculus), we found that both species exhibited an
acute inflammatory response, with scarring characterized by stronger
myeloperoxidase activity. In contrast, ROS production was stronger and more
persistent during regeneration. By depleting macrophages during injury, we
demonstrate a functional requirement for these cells to stimulate regeneration.
Importantly, the spatial distribution of activated macrophage subtypes was unique
during regeneration with pro-inflammatory macrophages failing to infiltrate the
regeneration blastema. Together, our results demonstrate an essential role for
inflammatory cells to regulate a regenerative response.
PMID- 28508753
TI - Endometriosis in the setting of Muckle-Wells syndrome treated with an IL-1beta
antagonist.
PMID- 28508754
TI - Postoperative maxillary cyst presenting as a skin tumour on the cheek.
PMID- 28508755
TI - Desmoplastic fibroblastoma: an unusual dermal presentation on the buttock of a
patient with muscular dystrophy.
PMID- 28508756
TI - A solid variant of primary cutaneous cribriform carcinoma: a small, stable, long
term lesion.
PMID- 28508757
TI - Unilateral nevoid telangiectasia: a condition unmasked by hyperoestrogenism?
PMID- 28508758
TI - Cutaneous larva migrans: a case in Bordeaux, France and a systematic review of
locally acquired cases in Europe.
PMID- 28508759
TI - MRI-TRUS fusion for electrode positioning during irreversible electroporation for
treatment of prostate cancer.
AB - We aimed to introduce an approach for image-guided positioning of electrodes for
irreversible electroporation (IRE) in patients with prostate cancer using a
magnetic resonance imaging-transrectal ultrasonography (MRI-TRUS) fusion
technique. In 10 consecutive patients with biopsy-proven Gleason score <=3+4
prostate cancer, 19 G electrodes were inserted into the prostate using a
transperineal access. Magnetic resonance images of the prostate acquired before
IRE were fused with transrectal ultrasound images acquired during IRE. The
position of the ultrasound probe was tracked via a sensor and corresponding
magnetic resonance images were calculated in real-time. While MRI allowed
delineation of the target volume, the position of the electrodes could be
visualized on ultrasound images; the distance between individual electrode pairs
was measured. Based on these measurements the software installed on the IRE unit
was able to calculate the voltage necessary to generate the electric field for
ablation. Using contrast-enhanced ultrasound, changes in perfusion within the
ablation zone after IRE were documented. This technique allowed positioning of
the electrodes around the target volume under image guidance in all patients
treated with IRE. The target lesion and a safety margin were covered within the
estimated ablation zone. MRI-TRUS guidance for IRE combines the advantages of
good visualization of the target lesion on MRI with the ability of ultrasound to
acquire imaging in real-time with a mobile device.
PMID- 28508760
TI - Radiologic and histopathologic review of rare benign and malignant breast
diseases.
AB - High social awareness of breast diseases and the rise in breast imaging
facilities have led to an increase in the detection of even rare benign and
malignant breast lesions. Breast lesions are associated with a broad spectrum of
imaging characteristics, and each radiologic imaging technique reflects different
characteristics of them. We aimed to increase familiarity of the radiologist with
these uncommon lesions as well as correlate histopathologic findings with the
radiologic imaging features of the tumors. Histopathologic examination is
necessary in the evaluation of such breast lesions, particularly when radiologic
images are not definitive for a specific diagnosis.
PMID- 28508761
TI - Posterior Branches of Lumbar Spinal Nerves - part II: Lumbar Facet Syndrome -
Pathomechanism, Symptomatology and Diagnostic Work-up.
AB - Posterior branches of the lumbar spinal nerves are the anatomic substrate of pain
in the lower back, sacrum and the gluteal area. Such pain may be associated with
various pathologies which cause pain in the posterior branches of the lumbar
spinal nerves due to entrapment, mechanical irritation or inflammatory reaction
and/or degeneration. The posterior branches are of significant functional
importance, which is related to the function of the structures they supply,
including facet joints, which are the basic biomechanical units of the spine. Low
back pain caused by facet joint pathology may be triggered e.g. by simple
activities, such as body rotations, unnatural positions, lifting heavy weights or
excessive bending as well as chronic overloading with spinal hyperextension. Pain
usually presents at the level of the lumbosacral junction (L 5 -S 1 ) and in the
lower lumbar spine (L 4-5 , L 3-4 ). In the absence of specific diagnostic
criteria, it is only possible to conclude that patients display tenderness at the
level of the affected facet joint and that the pain is triggered by extension.
Differential diagnosis for low back pain is difficult, since the pain may
originate from various structures. The most reliable method of identifying Lumbar
Facet Syndrome has been found to be a positive response to an analgesic procedure
in the form of a block of the medial branch or intraarticular injection. There
appear to be good grounds for conducting further studies and developing
unequivocal diagnostic tests.
PMID- 28508762
TI - Results of the Treatment of Infected Nonunions of the Lower Limbs Using the
Ilizarov Method.
AB - BACKGROUND: Infected nonunion is a complex complication of the treatment of long
bone fractures. An in creased incidence of injuries, including high energy
injuries (often open ones), contributes to a higher incidence of nonunion. These
primarily infected injuries cause osteomyelitis, which prevents bone union,
resulting in an infected nonunion. The Ilizarov method meets the biological and
biomechanical treatment requirements, opti mising the process of inflammation
healing and producing bone union. MATERIAL AND METHODS: A total of 54 patients
were treated in 2000-2014 for nonunion in the lower limbs with the Ilizarov
method, which was used after previous treatment had failed. The subjects
underwent intra operative resection of the locus of infection, sequestrectomy and
a Judet procedure, followed by the use of the Ilizarov apparatus and bone
transport, depending on the defect. RESULTS: Inflammation healed in 52 patients
(96%) and bone union was achieved in 46 patients (86%). Good outcomes with healed
inflammation and bone union were reported in 76% of the cases, fair outcomes with
tem porary elimination of the inflammation and without bone union in 16%, and
poor outcomes without inflam ma tion healing and without bone union in 7%.
CONCLUSIONS: Treatment of infected nonunion can only be effective after
eliminating endogenous inflamma tory foci, covering skin defects, ensuring a good
condition of the skin and soft tissues, restoring normal blood supply to the bone
fragments, and good biomechanical fixation of the fragments with dynamisation or
compression. The Ilizarov method is a method of choice in the treatment of cases
of infected nonunion where other treatments have failed.
PMID- 28508763
TI - Radiological Outcomes of Overhead Traction Therapy for Developmental Dysplasia of
the Hip in Non-ambulatory Children.
AB - BACKGROUND: Infants with a dislocated and unstable hip that does not lend itself
to stabilisation may be treated using overhead traction to achieve gradual
reduction of the hip joint. The aim of this paper was to analyse the radiological
outcomes of overhead traction therapy and the effect of duration of traction on
the occurrence of complications and final treatment outcomes. Material and
methodd. A retrospective analysis of medical records of 26 children (34 affected
hips) involved three independent observers assessing radiological parameters
before the surgery and at follow-up visits at least two years after the therapy.
RESULTS: Overhead traction was used for an average of 35 days (range: 15-43
days). Twenty six hips were treated solely with reduction and immobilisation in a
'human position' plaster cast. Three hips were qualified for surgery immediately
after a preliminary traction period. Five hips showed a suboptimal result
following the immobilisation period. A MANOVA model revealed that the following
factors had a significant effect on the treatment outcome: superior centring
ratio of Smith (with the lowest values recorded in patients with residual hip
dysplasia, p = 0.001) and acetabular angle of Sharp (with the lowest values found
in patients requiring surgery, p = 0.01). Statistical tests did not show a
correlation between the duration of traction and disturbance of proximal femoral
metaphysis growth assessed according to Bucholz and Ogden classification. Fifteen
hips were classified as type I, eight hips were graded as type II and also eight
hips as type III. CONCLUSIONS: The lowest values of acetabular angle of Sharp
were recorded in patients requiring surgery and the lowest superior centring
ratio of Smith was found in those with residual hip dysplasia. The duration of
overhead traction did not directly correlate with the final outcome; it only
seemed to be an indicator of the severity of hip dysplasia. Routine use of
overhead traction before undertaking closed reduction does not probably decrease
the incidence of proximal femoral growth disturbance.
PMID- 28508764
TI - Current Incidence of Different Morphological Types of Malignant Metastases to the
Spine Based on Magnetic Resonance Imaging.
AB - BACKGROUND: Malignant tumours particularly often metastasise to the spine,
causing considerable pain and limiting the patient's physical function. Standard
therapy consists in surgical treatment with adjuvant radiotherapy. The
qualification for surgery is a multifaceted process and detailed analysis of the
morphology of the metastasis is a key factor. Numerous types of classification of
metastatic lesions exist, among which the Tomita system, based on MRI findings,
appears to be the most practical. The aim of this paper is to present the current
incidence of different morphological types of metastases as classified by the
Tomita system. MATERIALS AND METHODS: This work was based on cases treated at the
Department of Oncological Orthopaedics of the Specialist Hospital in Brzozow -
Podkarpacie Oncological Centre from 2010-2015. A total of 854 patients with
spinal metastases were hospitalised at the department. All patients underwent a
CT and MRI of the spine and their metastatic lesions were classified as one of
the 7 types described by Tomita. The incidence of different morphological types
of metastases per type of the primary tumour was also determined. RESULTS: Most
patients treated at the department had advanced disease as a result of diagnostic
delays. Types T3-T7 were found in 91% of the patients and T7 in 44%. The highest
incidence of advanced disease was seen among patients with breast cancer and
myeloma. Higher pain severity and incidence of neurological complications were
noted in patients with multisite lesions. Neurological deficits were diagnosed in
228 patients, of whom 68% were classified as Type T6 or T7. Most of the T6/T7
patients were unable to walk unassisted and required constant help from their
family or medical staff. CONCLUSIONS: The Tomita system allows for easy and clear
classification of the morphology of malignant metastases. 66% of patients treated
at our department had multisite T6 or T7 metastases.
PMID- 28508765
TI - A Comparison of Outcomes of Treatment with Resection Prosthesis of the Hip in
Revision and Oncological Surgery.
AB - INTRODUCTION: The introduction of resection prostheses paved the way for the
development of limb-sparing surgery in patients with primary or metastatic bone
tumours. After some time, the developing possibilities of treatment of extensive
bone defects allowed for the use of resection prostheses as an emergency
procedure in patients undergoing revision surgery due to hip implant loosening.
The aim of this paper is to compare treatment outcomes in patients receiving the
Modular Universal Tumour and Revision System (MUTARS) resection prosthesis during
arthroplasty performed for different indications: treatment of a tumour
metastasis and revision surgery in cases of implant loosening. MATERIAL AND
METHODS: A total of 34 MUTARS femoral resection prostheses were implanted in 34
patients at the Cracow Centre of Rehabilitation and Orthopaedics between December
2008 and January 2016. The procedure was indicated due to the presence of a
tumour metastasis (in 13 cases) or due to implant loosening that required
revision arthroplasty with a resection prosthesis (in 21 cases). Femoral bone
defects were classified according to Paprosky and Katthagen in all operated
patients. Clinical assessment was conducted with the modified Harris Hip Score
before the surgery and at one year after the procedure. In addition, pain
intensity was assessed with a Visual Analogue Scale (VAS). RESULTS: No
statistically significant differences were observed between the groups with
respect to the length of the femoral bone resected, perioperative blood loss and
the number of packed red blood cell (PRBC) units required. A statistically
significant difference was found in duration of the surgery and hospital stay,
which were longer in the revision arthroplasty group. No statistically
significant differences were observed between the groups in the post-operative
HHS scores and pain assessment in the VAS scale. The revision arthroplasty group
showed significantly more dislocations (8 vs. 2) and cases of surgical site
infection. CONCLUSIONS: 1.The use of the MUTARS modular resection prosthesis
allows for fast clinical improvement that meets the patient's expectations both
in oncological treatment and in revision arthroplasty. 2. The extent of bone
resection, procedure duration and perioperative blood loss associated with the
surgical placement of a resection prosthesis are similar in oncological treatment
and in revision arthroplasty. 3. The use of a resection prosthesis in revision
arthroplasty is associated with a high risk of implant dislocation.
PMID- 28508766
TI - Comparison of Quality of Life of Patients after Hip Disarticulation and Those
after Stump Lengthening with Modular Prosthesis.
AB - BACKGROUND: Disarticulation has been used less and less often in the treatment of
musculoskeletal neoplasms; however, in some cases it allows the patient to
achieve good oncological and functional outcomes. The aim of this paper is to
present the possibilities, surgical technique and treatment outcomes of patients
after hip disarticulation and stump lengthening with a modular prosthesis.
MATERIAL AND METHODS: Three classic hip disarticulation surgeries and 2 hip
disarticulation procedures with stump lengthening with a modular prosthesis were
performed at the Department of Oncological Orthopaedics in Brzozow in 2013 and
2014. The present paper discusses the indications, surgical technique and
outcomes. Pain intensity was assessed in a VAS scale and physical function was
measured with the Karnofsky scale. The mental status of the patients was analysed
in the Beck Depression Inventory and the ability to perform daily living
activities was evaluated according to Katz. The ability to walk after surgery was
assessed. RESULTS: Patients after hip disarticulation showed considerably worse
functional outcomes. The mean physical function score was 53 points in the
Karnofsky scale and 3.33 points in the Katz scale. The patients had difficulty
walking and did not ambulate with their prostheses. They reported problems with
sitting and using the toilet. Patients with lengthened stumps showed visibly
better physical function scores, achieving, on average, 65 points in the
Karnofsky scale and 5.5 points in the Katz scale. These patients used their
prostheses, ambulated efficiently and were independent. CONCLUSIONS: Stump
lengthening with a modular prosthesis in patients after hip disarticulation
results in significantly better outcomes than the classic procedure.
PMID- 28508767
TI - Biopsychosocial Rehabilitation Programme for Patients with Chronic Back Pain.
Pilot Study.
AB - BACKGROUND: In the search for effective and comprehensive therapies of back pain,
an increasing emphasis in being placed on the biopsychosocial model and
multidimensional support programmes for patients as well the use of modern
technologies in this area of medicine. This study aimed to assess a programme of
customised ad hoc physiotherapeutic consultations for patients with back pain who
had been on the waiting list for rehabilitation treatment for a long time.
MATERIAL AND METHOD: The study group comprised 68 patients of the Rehabilitation
Centre Non-Public Health Care Institution who had been waiting for rehabilitation
treatment for at least three months. The patients, diagnosed with chronic back
pain and aged 40-80 years, were randomly assigned into two groups. The
experimental group took part in a programme of three consultations, provided on
average once a month. The patients from both groups were assessed after the three
month programme, immediately before the commencement of the prescribed
rehabilitation treatment. We evaluated the pain threshold at trigger points of
selected muscles using the algometric method (kg/cm 2 ), subjective assessment of
pain (VAS), functional limitations (Rolland Morris Disability Questionnaire) and
quality of life (36-Item Short Form Health Survey, SF-36). The statistical
analysis of the results used non-parametric methods: significance of differences
between the groups was evaluated with the Mann-Whitney U test and correlations
between the variables were assessed separately for each group using Spearman's
rank order correlation. The significance threshold was accepted at alpha=0.05.
RESULTS: The algometric evaluation of all the muscles revealed significantly
lower sensitivity to pain, demonstrated by a higher pain threshold (p<0.0001), in
the experimental group. Moreover, this group also included a much smaller
percentage of patients with a high level of functional limitations according to
the Rolland Morris Disability Questionnaire. The quality of life evaluation
revealed that the control group scored poorer in the mental domain (p=0.02).
CONCLUSIONS: The ad hoc intervention programme for patients referred for
rehabilitation due to chronic back pain showed demonstrable beneficial effects
with regard to their psychophysical health. Similar programmes should be more
readily offered to patients at health care centres and implemented into clinical
practice.
PMID- 28508768
TI - Inveterate (42-year-old) Hip Dislocation Treated with Arthroplasty. A Case Study.
AB - Dislocation of the hip usually results from a high-energy injury sustained during
a road accident. Inveterate dislocations persisting for many months or years are
extremely rare. Selection of an appropriate treatment method is not easy and is
always associated with the risk of serious complications. The present authors
hope that a description of the course of diagnostic work-up and treatment of a
patient in whom a hip dislocation persisted for 42 years will prove interesting
and helpful for orthopaedists who may encounter such a case in their practice.
The patient sustained a dislocation of the right hip in 1974. He did not agree to
undergo reduction immediately after the injury. Initially, he experienced
extremely severe pain and difficulty walking, but gradually learned to walk
without crutches and even took up a job. The limb was considerably shortened with
only minimal movement in the hip joint. The pelvic geometry was altered and
spinal scoliosis developed. In the last several years, the patient experienced a
significant increase in pain and a decrease in function that prevented him from
walking unassisted. Following a thorough physical examination, and based on
computed tomography images, the patient was qualified for hip arthroplasty. An
analysis of the available literature prompted the present authors to use a
cemented implant and not to use bone grafts. Early treatment outcomes are good.
PMID- 28508769
TI - Diagnostic Difficulties in Bone Sarcoidosis Imaging. A Cases Study.
AB - Sarcoidosis is a multiorgan inflammatory disease that rarely involves the
musculoskeletal system. A typical radiographic presentation is only noted with
phalangeal lesions in the hands and feet, and other skeletal sites of sarcoidosis
are a diagnostic imaging challenge [1]. We describe two cases of patients with
sarcoidosis in whom pathologic bone marrow lesions were diagnosed on MRI scans.
The magnetic resonance findings were non-specific and metastatic lesions or
multiple myeloma were suspected. The case analysis serves to point to limitations
of imaging studies in diagnosing bone sarcoidosis and underline the importance of
cooperation between the radiologist and the clinician. The role of magnetic
resonance imaging in the diagnostic algorithm for bone sarcoidosis should mostly
focus on locating lesions, indicating biopsy sites and follow-up of
abnormalities.
PMID- 28508770
TI - Romuald Weglowski (1876-1935) - Orthopaedic Surgeon, Forgotten Pioneer of Limb
Saving Tumour Surgery.
AB - On May 16, 1914, The Lancet Journal published a paper by Romuald Weglowski, a
Polish-born professor of Moscow University, entitled "Malignant tumours of bones:
a new method in conservative operative treatment." The idea of biological
resection presented in the paper consisted in thermocoagulation of the apparently
cancerous part of a bone with a jet of steam. According to the author, dead bone
rid of live malignant cells reconstructed itself quickly, which helped to
preserve the functionality of the organ without considerable limitations. The
events of the First World War, political changes in tsarist Russia and the
recovery of independence by Poland greatly complicated Weglowski's professional
career. We thought it would be interesting to present the life story of the great
Polish surgeon in the context of his own method of bone cancer treatment, which
without doubt marked the beginning of Polish orthopaedic oncology aimed at limb
saving surgery.
PMID- 28508771
TI - Alkylthiol self-assembled monolayers on Au(111) with tailored tail groups for
attaching gold nanoparticles.
AB - Self-assembled monolayers (SAMs) on Au(111) are able to control the functionality
of a gold surface. We use scanning tunnelling microscopy (STM) in air and contact
angle measurements to compare the morphology and the chemistry of three
alkylthiol SAMs differing by their tail groups: 1,9-nonanedithiol (NDT), 1,4
butanedithiol (BDT) and 11-mercaptoundecanol (MUOH). STM reveals very different
morphologies: a hexagonal lattice for MUOH and parallel rows for NDT and BDT. In
the case of NDT, we find that the thiol tail groups may form disulfide bridges
with long immersion times. The availability of the -SH group for chemical
reactions is demonstrated by attaching gold nanoparticles (AuNPs). When the thiol
tail group is available, AuNPs readily attach as shown with atomic force
microscopy (AFM). When disulfide bridges are formed, the gold surface is not able
to bind nanoparticles.
PMID- 28508772
TI - Concept-Based Retrieval from Critical Incident Reports.
AB - BACKGROUND: Critical incident reporting systems (CIRS) are used as a means to
collect anonymously entered information of incidents that occurred for example in
a hospital. Analyzing this information helps to identify among others problems in
the workflow, in the infrastructure or in processes. OBJECTIVES: The entire
potential of these sources of experiential knowledge remains often unconsidered
since retrieval of relevant reports and their analysis is difficult and time
consuming, and the reporting systems often do not provide support for these
tasks. The objective of this work is to develop a method for retrieving reports
from the CIRS related to a specific user query. METHODS: atural language
processing (NLP) and information retrieval (IR) methods are exploited for
realizing the retrieval. We compare standard retrieval methods that rely upon
frequency of words with an approach that includes a semantic mapping of natural
language to concepts of a medical ontology. RESULTS: By an evaluation, we
demonstrate the feasibility of semantic document enrichment to improve recall in
incident reporting retrieval. It is shown that a combination of standard keyword
based retrieval with semantic search results in highly satisfactory recall
values. CONCLUSION: In future work, the evaluation should be repeated on a larger
data set and real-time user evaluation need to be performed to assess user
satisfactory with the system and results.
PMID- 28508773
TI - Word Sense Disambiguation of Medical Terms via Recurrent Convolutional Neural
Networks.
AB - BACKGROUND: Tagging text data with codes representing biomedical concepts plays
an important role in medical data management and analysis. A problem occurs if
there are ambiguous words linked to several concepts. OBJECTIVES AND METHODS:
This study aims at investigating word sense disambiguation based on word
embedding and recurrent convolutional neural networks. The study focuses on terms
mapped to multiple concepts of the Unified Medical Language System (UMLS).
RESULTS: We created 20 text processing pipelines trained on a subset of the MeSH
Word Sense Disambiguation (MSH WSD) data set, each pipeline disambiguating the
sense of one word. The pipelines were then tested on a disjoint subset of MSH WSD
data. Most pipelines achieved good or even excellent results (70% of the
pipelines achieved at least 90% accuracy, 40% achieved at least 98% accuracy).
One poor-performing outlier was detected. CONCLUSION: The proposed approach can
serve as a basis for an up-scaled system combining pipelines for many ambiguous
words. The methods used here recently proved very successful in other fields of
text understanding and can be expected to scale-up with improved availability of
training data.
PMID- 28508774
TI - Arden Syntax MLM Building Blocks for Microbiological Concepts and Their
Application in Infection Surveillance.
AB - BACKGROUND: The diagnosis - and hence definitions - of healthcare-associated
infections (HAIs) rely on microbiological laboratory test results in specific
constellations. OBJECTIVES: To construct a library that provides interoperable
building blocks for the analysis of microbiological laboratory test results.
METHODS: We used Java for preprocessing raw microbiological laboratory test
results and Arden Syntax for knowledge-based querying of data based on
microbiology information elements used in European surveillance criteria for
HAIs. To test the library and quantify how often these information elements occur
in the data, we performed a retrospective cohort study on adult patients admitted
for at least 24 hours to an intensive care unit at the Vienna General Hospital in
2013. RESULTS: We identified eleven information elements for which information
was electronically available. These elements were identified positively 1,239
times in 1,184 positive microbiology tests from 563 patients. DISCUSSION: The
availability of a library for the analysis of microbiology laboratory test
results in HAI terms facilitates electronic HAI surveillance.
PMID- 28508775
TI - Semantic Technologies for Re-Use of Clinical Routine Data.
AB - Routine patient data in electronic patient records are only partly structured,
and an even smaller segment is coded, mainly for administrative purposes. Large
parts are only available as free text. Transforming this content into a
structured and semantically explicit form is a prerequisite for querying and
information extraction. The core of the system architecture presented in this
paper is based on SAP HANA in-memory database technology using the SAP Connected
Health platform for data integration as well as for clinical data warehousing. A
natural language processing pipeline analyses unstructured content and maps it to
a standardized vocabulary within a well-defined information model. The resulting
semantically standardized patient profiles are used for a broad range of clinical
and research application scenarios.
PMID- 28508776
TI - Development and Validation of a Multivariable Prediction Model for the Occurrence
of Delirium in Hospitalized Gerontopsychiatry and Internal Medicine Patients.
AB - Delirium is an acute confusion condition, which is common in elderly and often
misdiagnosed in hospitalized patients. Early identification and prevention of
delirium could reduce morbidity and mortality rates in those affected and reduce
hospitalization costs. We have developed and validated a multivariate prediction
model that predicts delirium and gives an early warning to physicians. A large
set of patient electronic medical records have been used in developing the
models. Classical learning algorithms have been used to develop the models and
compared the results. Excellent results were obtained with the feature set and
parameter settings attaining accuracy of 84%.
PMID- 28508777
TI - How to Link SNOMED CT Procedure and WHO International Classification of Health
Interventions (ICHI).
AB - Among different used healthcare terminology resources there is a need to link
them to ease their interoperability. SNOMED CT is the most detailed clinical
reference terminology for procedure used in the Electronic Health Record (EHR).
WHO developed since 2006 an aggregated classification named ICHI required for
statistics and resource allocation. It is based on an ontology framework defined
in ISO 1828 named Categorial Structure (CAST) for surgical procedures. We present
ICHI coding structure, ISO 1828 CAST standard for surgical procedures and SNOMED
CT procedures hierarchy concept model and their relations. We demonstrate the
obstacles to align ICHI coding structure with ISO 1828 CAST which can be linked
with SNOMED CT procedures hierarchy concept model. We recommend to update ICHI
coding structure to decrease the gap with ISO 1828 CAST and SNOMED CT concept
model for procedures hierarchy to allow users to share the different terminology
resources.
PMID- 28508778
TI - Supporting Molecular Tumor Boards in Molecular-Guided Decision-Making - The
Current Status of Five German University Hospitals.
AB - BACKGROUND: German university hospitals have started to establish molecular tumor
boards in order to enable physicians to make molecular-guided decisions.
OBJECTIVE: Our aim was to describe the organizational structure and procedures
which are currently supporting the molecular tumor boards of five German
university hospitals. METHODS: We conducted semi-structured interviews with
experts of five university hospitals between December 2016 and February 2017.
RESULTS: We observed heterogeneity in both the organization of genetic testing
and the management of the molecular tumor boards among the five hospitals. They
used free-text documents in most of their support procedures rather than machine
readable documents. CONCLUSION: There are three potentialities to support the
process from genetic testing to reporting within the molecular tumor boards: (i)
standardized pipeline to integrate automated variant calling and annotation; (ii)
tools supporting the experts in creating their reports and presentations and
(iii) implementing pharmacogenomic CDSS into clinical routine.
PMID- 28508779
TI - Ad hoc Participation in Professional Tele-Collaboration Platforms.
AB - Tele-collaboration between medical professionals is well established for
specialties like radiology, cardiology or pathology. Typically these applications
do not allow for ad hoc participation of non-registered users like patients and /
or medical professionals. This paper describes an approach for extending these
tele-applications to non-registered users and providing ad hoc participation with
means for providing and accessing data. A light weight, web-based approach is
used to assure acceptance and ease of use while maintaining and complying to the
required regulations regarding authentication, authorization and protection of
personal data. The approach has been implemented and is in use with a nationwide
tele-collaboration network in Germany.
PMID- 28508780
TI - Challenges and Approaches to Make Multidisciplinary Team Meetings Interoperable -
The KIMBo Project.
AB - BACKGROUND: Multidisciplinary team meetings (MDTMs) are already in use for
certain areas in healthcare (e.g. treatment of cancer). Due to the lack of common
standards and accessibility for the applied IT systems, their potential is not
yet completely exploited. OBJECTIVES: Common requirements for MDTMs shall be
identified and aggregated into a process definition to be automated by an
application architecture utilizing modern standards in electronic healthcare,
e.g. HL7 FHIR. METHODS: To identify requirements, an extensive literature review
as well as semi-structured expert interviews were conducted. RESULTS: Results
showed, that interoperability and flexibility in terms of the process are key
requirements to be addressed. An architecture blueprint as well as an aggregated
process definition were derived from the insights gained. To evaluate the
feasibility of identified requirements, methods of explorative prototyping in
software engineering were used. CONCLUSION: MDTMs will become an important part
of modern and future healthcare but the need for standardization in terms of
interoperability is imminent.
PMID- 28508781
TI - Two Years of tranSMART in a University Hospital for Translational Research and
Education.
AB - BACKGROUND: For translational research, software platforms such as tranSMART with
an integrated view of both clinical and omics data have gained more and more
attention in the last years. OBJECTIVES: We wanted to examine the success and
failures of tranSMART in the fields of translational research and education by
looking at the examples of six use cases at our hospital. We wanted to point out
suitable scenarios and user groups as well as still existing challenges and
limitations. METHODS: We sum up the experience we made with our use cases with a
focus on lessons learned. RESULTS: tranSMART was successfully established by a
bottom-up approach at our university hospital and has been running for more than
two years now. It has been used in four translational research projects as well
as in education in the context of lectures and bachelor/master theses.
CONCLUSION: tranSMART can be a very useful tool for translational research and
education. But it should be used with both care and statistical knowledge to
avoid wrong conclusions. Some technical constraints, especially for data
modeling, still limit many applications. Version control and data provenance are
remaining challenges.
PMID- 28508782
TI - The Use of RESTful Web Services in Medical Informatics and Clinical Research and
Its Implementation in Europe.
AB - BACKGROUND: RESTful web services nowadays are state-of-the-art in business
transactions over the internet. They are however not very much used in medical
informatics and in clinical research, especially not in Europe. OBJECTIVES: To
make an inventory of RESTful web services that can be used in medical informatics
and clinical research, including those that can help in patient empowerment in
the DACH region and in Europe, and to develop some new RESTful web services for
use in clinical research and regulatory review. METHODS: A literature search on
available RESTful web services has been performed and new RESTful web services
have been developed on an application server using the Java language. RESULTS:
Most of the web services found originate from institutes and organizations in the
USA, whereas no similar web services could be found that are made available by
European organizations. New RESTful web services have been developed for LOINC
codes lookup, for UCUM conversions and for use with CDISC Standards. DISCUSSION:
A comparison is made between "top down" and "bottom up" web services, the latter
meant to answer concrete questions immediately. The lack of RESTful web services
made available by European organizations in healthcare and medical informatics is
striking. CONCLUSION: RESTful web services may in short future play a major role
in medical informatics, and when localized for the German language and other
European languages, can help to considerably facilitate patient empowerment. This
however requires an EU equivalent of the US National Library of Medicine.
PMID- 28508783
TI - Automatic Conversion of Metadata from the Study of Health in Pomerania to ODM.
AB - BACKGROUND: Electronic collection and high quality analysis of medical data is
expected to have a big potential to improve patient care and medical research.
However, the integration of data from different stake holders is posing a crucial
problem. The exchange and reuse of medical data models as well as annotations
with unique semantic identifiers were proposed as a solution. OBJECTIVES: Convert
metadata from the Study of Health in Pomerania to the standardized CDISC ODM
format. METHODS: The structure of the two data formats is analyzed and a mapping
is suggested and implemented. RESULTS: The metadata from the Study of Health in
Pomerania was successfully converted to ODM. All relevant information was
included in the resulting forms. Three sample forms were evaluated in-depth,
which demonstrates the feasibility of this conversion. CONCLUSION: Hundreds of
data entry forms with more than 15.000 items can be converted into a standardized
format with some limitations, e.g. regarding logical constraints. This enables
the integration of the Study of Health in Pomerania metadata into various
systems, facilitating the implementation and reuse in different study sites.
PMID- 28508784
TI - VR Medical Gamification for Training and Education.
AB - The new virtual reality based medical applications is providing a better
understanding of healthcare related subjects for both medical students and
physicians. The work presented in this paper underlines gamification as a concept
and uses VR as a new modality to study the human skeleton. The team proposes a
mobile Android platform application based on Unity 5.4 editor and Google VR SDK.
The results confirmed that the approach provides a more intuitive user experience
during the learning process, concluding that the gamification of classical
medical software provides an increased interactivity level for medical students
during the study of the human skeleton.
PMID- 28508785
TI - Assessing the Educational Needs of Health Information Management Staff of the
Mashhad University of Medical Sciences, Iran.
AB - Health information management (HIM) professionals have a combination of skills
and, at the same time, the demand for their skills in the health system is
increasing rapidly. This study aimed to assess the educational needs of the HIM
staff in Iran. This descriptive analytical study was conducted in eight teaching
hospitals. It was found that the maximum educational needs concerned the
knowledge of medical terminology, occupational safety, legal aspects, the newest
rules and regulations, and ministry guidelines, while the least of the felt needs
related to insurance and other aspects of registry, data ownership, and data
quality. The need to learn about coding and classifications had a significant
relationship with work experience (P = 0.045) and those with a work experience of
6 to 10 years had fewer needs. Educational needs were also significantly
associated with the number of years since graduation (P = 0.005), as those with 5
10 years' experience after post-graduation had lesser needs than others. Those
who plan educational programs for health information professionals must have a
comprehensive view of the needs of the health system. Participation of
specialists of different fields must be considered in educational planning of
such interdisciplinary fields.
PMID- 28508786
TI - Implementation of Nationwide Electronic Health Record in Albania: A Case Study.
AB - BACKGROUND: This paper presents a case study of the nationwide implementation of
an Electronic Health Record system based on industry standards. OBJECTIVES: To
critically review the finalized nationwide EHR implementation in Albania,
pointing out the achievements and the shortcomings, gained knowledge and sharing
lessons learned. METHODS: This paper reports on our analysis of the project's
documentation, first-hand experience working with healthcare professionals during
and after project implementation. The initial system uptake analysis has been
made using EHR usage statistics. RESULTS: Despite very poor initial ICT
infrastructure, minimal or non-existing medical nomenclature and a rather
challenging project schedule, the nationwide implementation of the EHR system was
successfully completed in less than two years. CONCLUSION: Although the system is
already in use by 79 healthcare providers and is covering secondary and tertiary
care, the majority of clinical data still remains in paper format; the access for
clinicians to the system is limited due to insufficient ICT infrastructure.
PMID- 28508787
TI - The Importance of Gene-Drug-Drug-Interactions in Pharmacogenomics Decision
Support: An Analysis Based on Austrian Claims Data.
AB - While pharmacogenomic testing combined with clinical decision support has the
potential to increase the safety and efficacy of medical treatments, the intake
of multiple prescription drugs can - if not sufficiently addressed by decision
support solutions - impair the effectiveness of such interventions by modulating
the capacity of precisely those enzymes whose function pharmacogenomic tests try
to predict. We quantified the potential extent of such drug-mediated mismatches
between genotype-derived phenotypes and real phenotypes, commonly called
"phenoconversion", by screening claims data from 1,587,829 Austrian health
insurance holders of the years 2006 and 2007 for concomitant prescriptions of
drugs that can be dosed based on pharmacogenomics, and drugs that modulate enzyme
activity. In total, 232,398 such prescription overlaps were detected, of which
more than half (54.6%) could be attributed to co-prescriptions of moderate or
strong modulators. Our results indicate that prescription drug-mediated
phenoconversion is not uncommon, and should therefore be adequately reflected in
decision support solutions by integrating algorithms to detect potential gene
drug-drug interactions.
PMID- 28508788
TI - KALIS - An eHealth System for Biomedical Risk Analysis of Drugs.
AB - BACKGROUND: In Germany, adverse drug reactions and events cause hospitalizations,
which lead to numerous thousands of deaths and several million Euros in
additional health costs annually. OBJECTIVES: Approximately one in two deaths
could be avoided by an appropriate system for risk analysis of drugs. METHODS:
The integration and storage of several data sources from life sciences are an
ongoing need to address various questions with respect to drug therapy. A
software architecture for data integration was implemented in order to build up a
new data warehouse named KALIS-DWH, which includes pharmacological, biomolecular
and patient-related data. RESULTS: Based on this comprehensive KALIS-DWH, an
eHealth system named KALIS for biomedical risk analysis of drugs was implemented.
The task-specific modules of KALIS offer efficient algorithms for analyzing
medication and supporting decision-making in drug therapy. CONCLUSION: KALIS is
meant to be a web-based information system for health professionals and
researchers. KALIS provides comprehensive knowledge and modules for risk analysis
of drugs, which can contribute to minimizing prescribing errors.
PMID- 28508789
TI - Propose of Standards Based IT Architecture to Enrich the Value of Allergy Data by
Telemonitoring Data.
AB - Interoperability is a key requirement for any IT-System to be future proof and
cost efficient, due to the increasing interaction of IT-Systems in Healthcare.
This feasibility study is part of a larger project focusing on the
conceptualization and evaluation of interoperable and modular IT-Framework
components for exchanging big data information sets. Hence, this project
investigates the applicability of a standard based IT-Architecture for the
integration of Personal Health Devices data and open data sources. As a proof of
concept use case, pollen forecast data from the Medical University of Vienna were
combined with Personal Health Device data and a data correlation was
investigated. The standards were identified as well as selected in expert's
reviewed and the Architecture was designed based on a literature research.
Subsequently the prototype was implemented and successfully tested in
interoperability tests. The study shows that the architecture meets the
requirements. It can be flexibly extended according to further requirements due
to its generic setup. However, further extensions of the Interoperability
Connector and a full test setup needs to be realized in future.
PMID- 28508790
TI - Development of a Multidisciplinary and Telemedicine Focused System Database.
AB - BACKGROUND: Tele-rehabilitation at home is one of the promising approaches in
increasing rehabilitative success and simultaneously decreasing the financial
burden on the healthcare system. OBJECTIVES: Novel and mostly mobile devices are
already in use, but shall be used in the future to a higher extent for allowing
at home rehabilitation processes at a high quality level. The combination of
exercises, assessments and available equipment is the basic objective of the
presented database. METHODS: The database has been structured in order to allow
easy-to-use and fast access for the three main user groups. Therapists - looking
for exercise and equipment combinations - patients - rechecking their tasks for
home exercises - and manufacturers - entering their equipment for specific use
cases. RESULTS: The database has been evaluated by a proof of concept study and
shows a high degree of applicability for the field of rehabilitative medicine.
Currently it contains 110 exercises/assessments and 111 equipment/systems.
CONCLUSION: Foundations of presented database are already established in the
rehabilitative field of application, but can and will be enhanced in its
functionality to be usable for a higher variety of medical fields and
specifications.
PMID- 28508791
TI - Rehabilitation Risk Management: Enabling Data Analytics with Quantified Self and
Smart Home Data.
AB - A variety of acute and chronic diseases require rehabilitation at home after
treatment. Outpatient rehabilitation is crucial for the quality of the medical
outcome but is mainly performed without medical supervision. Non-Compliance can
lead to severe health risks and readmission to the hospital. While the patient is
closely monitored in the hospital, methods and technologies to identify risks at
home have to be developed. We analyze state-of-the-art monitoring systems and
technologies and show possibilities to transfer these technologies into
rehabilitation monitoring. For this purpose, we analyze sensor technology from
the field of Quantified Self and Smart Homes. The available sensor data from this
consumer grade technology is summarized to give an overview of the possibilities
for medical data analytics. Subsequently, we show a conceptual roadmap to
transfer data analytics methods to sensor based rehabilitation risk management.
PMID- 28508792
TI - Identification of Cost Indicators with Significant Economic Impact on the Total
Treatment Costs of Chronic Heart Failure Patients - A Meta-Analysis.
AB - : Increasing treatment costs of HF patients affect the initiation of appropriate
treatment method. Divergent approaches to measure the costs of treatment and the
lack of common cost indicators impede the comparison of therapy settings.
OBJECTIVES: In the context of the present meta-analysis, key cost indicators from
the perspective of healthcare providers are to be identified, described, analyzed
and quantified. This review helps narrowing down the cost indicators, which have
the most significant economic impact on the total treatment costs of HF patients.
Telemedical services are to be compared to standard therapy methods. METHODS: The
identification process was based on several steps. For the quantitative
synthesis, we used the Preferred Reporting Items for Systematic Reviews and Meta
Analyses (PRISMA) statement. An additional set of criteria was defined for the
following qualitative analysis. RESULTS: 5 key cost indicators were identified
with significant economic impact on the treatment costs of HF patients.
CONCLUSION: 95% of the reported treatment costs could be captured based on the
identified cost indicators.
PMID- 28508793
TI - POSEIDON - Bringing Assistive Technology to People with Down Syndrome: Results of
a Three Year European Project.
AB - The POSEIDON project aimed to increase the independence and autonomy of people
with Down syndrome with the help of technical assistants. It followed a user
centered approach by involving people with Down syndrome and their parents,
carers etc. A requirement analysis was the first step of the project. It became
clear that people with Down syndrome especially need support in the areas of time
management, mobility and money handling. Different applications were developed
which were tested and evaluated in two field tests in three countries. Results
indicate that POSEIDON can help to overcome daily challenges and that it can
increase the autonomy and independence of people with Down syndrome.
PMID- 28508794
TI - On the Prototyping of an ICT-Enhanced Toilet System for Assisting Older Persons
Living Independently and Safely at Home.
AB - Standard toilets often do not meet the needs of a significant number of older
persons and persons with disabilities. The EU funded iToilet project aims at
design and development of a new type of ICT enhanced modular toilet system which
shall be able to support autonomy, dignity and safety of older persons living at
home. Methodologically the project started with gathering user requirements by
means of questionnaires, interviews and focus group discussion involving a total
of 74 persons, thereof 41 subjects with movement disorders (primary users), 21
caregivers (secondary users) and 12 healthcare managers (tertiary users). Most
important wishes were bilateral removable handrails, height and tilt adjustment,
emergency detection, simplicity. In parallel to the ongoing technical development
participatory design activities have been carried out at user test sites in order
to continuously involve users into the design process and to allow quick feedback
with regards to early prototype parts. The project currently is working on the
finalization of the first prototype ready to enter the lab trial stage in spring
2017. The experiences will be used for redesigning a prototype 2 which is planned
to be tested in real life settings early 2018.
PMID- 28508795
TI - Assistive Solutions in Practice: Experiences from AAL Pilot Regions in Austria.
AB - Since 2012 six AAL pilot regions were launched in Austria. The main goal of these
pilot regions is to evaluate the impact of AAL technologies in daily use
considering the entire value chain. Additionally, go-to market strategies for
assistive technologies based on an involvement of all relevant stakeholders are
developed. Within this paper an overview of the specific objectives, approaches
and the status of all Austrian AAL pilot regions is given. Taking into account
the different experiences of the different pilot regions, specific challenges in
establishing, implementing and sustaining pilot region projects are discussed and
lessons-learned are presented. Results show that a careful planning of all
project phases taking into account available resources is crucial for the
successful implementation of an AAL pilot region. In particular, this applies to
all activities related to the active involvement of end-users.
PMID- 28508796
TI - eMedication Meets eHealth with the Electronic Medication Management Assistant
(eMMA).
AB - BACKGROUND: A patient's healthcare team is often missing a complete overview on
the prescribed and dispensed medication. This is due to an inconsistent
information flow between the different actors of the healthcare system. Often,
only the patient himself knows exactly which drugs he is actually taking.
OBJECTIVES: Our objective is to exploit different eHealth technologies available
or planned in Switzerland to improve the information flow of the medication data
among the stakeholder and to support the patient in managing his medication.
METHODS: This work is embedded in the "Hospital of the Future Live" project,
involving 16 companies and 6 hospitals in order to develop IT solutions for
future optimized health care processes. A comprehensive set of requirements was
collected from the different actors and project partners. Further, specifications
of the available or planned eHealth infrastructure were reviewed to integrate
relevant technologies into a coherent concept. RESULTS: We developed a concept
that combines the medication list and an eHealth platform. The resulting
electronic medication management assistant (eMMA) designed for the patient
provides the current medication plan at any time and supports by providing
relevant information through a conversational user interface. CONCLUSION: In
Switzerland, we still need a bridging technology to combine the medication
information from the electronic patient record with the medication plan's
associated QR-Code. The developed app is intended to provide such bridge and
demonstrates the usefulness of the eMediplan. It enables the patient to have all
data regarding his medication on his personal mobile phone and he can - if
necessary - provide the current medication to the health professional.
PMID- 28508797
TI - A Web-Based Tool to Evaluate Data Quality of Reused Health Data Assets.
AB - BACKGROUND: Data from the health care domain is often reused to create and
parameterize simulation models for example to support life science business in
the evaluation of new products. Data quality assessments play an important part
to help model users in interpreting simulation results by showing deficiencies in
the raw data used in the model building and offers model builders a comparison of
data quality amongst the used data assets. OBJECTIVES: Assess data quality in raw
data prior to creating simulation models and prepare results for model users.
METHODS: Using a literature review and documentation of previous models created,
we searched data quality criteria. For eligible criteria we formulated questions
and viable answers to be used in a questionnaire to assess data quality of a data
asset. RESULTS: We developed a web tool to evaluate data assets using a generic
data model. Percentage results are visualized using a radar chart. CONCLUSION:
Data quality assessment with questionnaires offers model builders a framework to
critically analyse raw data and to detect deficiencies early in the modelling
process. The summarized results can help model users to better interpret
simulation results.
PMID- 28508798
TI - Frequent Treatment Sequence Mining from Medical Databases.
AB - The huge amount of data stored in healthcare databases allows wide range
possibilities for data analysis. In this article, we present a novel multilevel
analysis methodology to generate and analyze sequential healthcare treatment
events. The event sequences can be generated on different abstraction levels
automatically from the source data, and so they describe the treatment of
patients on different levels of detail. To present applicability of the proposed
methodology, we introduce a short case study as well, in which some analysis
results are presented arising from the analysis of a group of patients suffering
from colorectal cancer.
PMID- 28508799
TI - Comparison of Body Weight Trend Algorithms for Prediction of Heart Failure
Related Events in Home Care Setting.
AB - BACKGROUND: Automatic event detection is used in telemedicine based heart failure
disease management programs supporting physicians and nurses in monitoring of
patients' health data. OBJECTIVES: Analysis of the performance of automatic event
detection algorithms for prediction of HF related hospitalisations or diuretic
dose increases. METHODS: Rule-Of-Thumb and Moving Average Convergence Divergence
(MACD) algorithm were applied to body weight data from 106 heart failure patients
of the HerzMobil-Tirol disease management program. The evaluation criteria were
based on Youden index and ROC curves. RESULTS: Analysis of data from 1460
monitoring weeks with 54 events showed a maximum Youden index of 0.19 for MACD
and RoT with a specificity > 0.90. CONCLUSION: Comparison of the two algorithms
for real-world monitoring data showed similar results regarding total and limited
AUC. An improvement of the sensitivity might be possible by including additional
health data (e.g. vital signs and self-reported well-being) because body weight
variations obviously are not the only cause of HF related hospitalisations or
diuretic dose increases.
PMID- 28508800
TI - Electronic Health Records in Prehospital Care.
AB - Documentation is an essential part and duty in all clinical settings. "ELGA"
(short for "Elektronische Gesundheitsakte") is the Austrian Electronic Health
Record and aims to support the process of clinical decision-making. However the
use case of integrating ELGA to an out-of-hospital setting is not defined yet.
This work explores the special requirements in prehospital care. The aim of
research is to identify needed information and processes at the emergency scene
to establish appropriate decisions about diagnosis, treatments and transport.
Moreover the mentioned use case should be discussed by mapping available data
fields in ELGA to the required data at scene. To satisfy the research goal an
exploratory research using field work and expert interviews was done as well as a
systematic analysis of findings. The results were analyzed with a thematic
analysis approach and structured as flow charts, to illustrate the process, and
as an Entity-Relationship-Model, to show the required data at scene mapped to
available data fields in ELGA. It was possible to show that ELGA is suitable to
serve several use cases in prehospital care.
PMID- 28508801
TI - Adaptive Pump Speed Algorithms to Improve Exercise Capacity in Patients Supported
with a Left-Ventricular Assist Device.
AB - For the treatment of terminal heart failure, the therapy with left-ventricular
assist devices has already been established. In the systems used today, pump
speed does not adjust during physical activity so that cardiac output and
exercise capacity remain markedly limited. It is the aim of this study to develop
an automatic pump speed control based on filling pressure values in order to
improve exercise capacity and quality of life in these patients. Different
approaches are planned, to be tested in an in vitro patient simulator. The
algorithms aim to match the pump speed with the increased venous return. In
addition, preservation of aortic valve function should be taken into account.
PMID- 28508802
TI - Knowledge Engineering as a Component of the Curriculum for Medical Cybernetists.
AB - According to a new state educational standard, students who have chosen medical
cybernetics as their major must develop a knowledge engineering competency.
Previously, in the course "Clinical cybernetics" while practicing project-based
learning students were designing automated workstations for medical personnel
using client-server technology. The purpose of the article is to give insight
into the project of a new educational module "Knowledge engineering". Students
will acquire expert knowledge by holding interviews and conducting surveys, and
then they will formalize it. After that, students will form declarative expert
knowledge in a network model and analyze the knowledge graph. Expert decision
making methods will be applied in software on the basis of a production model of
knowledge. Project implementation will result not only in the development of
analytical competencies among students, but also creation of a practically useful
expert system based on student models to support medical decisions. Nowadays,
this module is being tested in the educational process.
PMID- 28508804
TI - eHealth Networking Information Systems - The New Quality of Information Exchange.
AB - BACKGROUND: The development and introduction of platforms that enable
interdisciplinary exchange on current developments and projects in the area of
eHealth have been stimulated by different authorities. OBJECTIVES: The aim of
this project was to develop a repository of eHealth projects that will make the
wealth of eHealth projects visible and enable mutual learning through the sharing
of experiences and good practice. METHODS: The content of the database and search
criteria as well as their categories were determined in close co-ordination and
cooperation with stakeholders from the specialist areas. Technically, we used
Java Server Faces (JSF) for the implementation of the frontend of the web
application. RESULTS: Access to structured information on projects can support
stakeholders to combining skills and knowledge residing in different places to
create new solutions and approaches within a network of evolving competencies and
opportunities. CONCLUSION: A regional database is the beginning of a structured
collection and presentation of projects, which can then be incorporated into a
broader context. The next step will be to unify this information transparently.
PMID- 28508803
TI - A First Standardized Swiss Electronic Maternity Record.
AB - BACKGROUND: During the nine months of pregnancy, women have to regularly visit
several physicians for continuous monitoring of the health and development of the
fetus and mother. Comprehensive examination results of different types are
generated in this process; documentation and data transmission standards are
still unavailable or not in use. Relevant information is collected in a paper
based maternity record carried by the pregnant women. OBJECTIVES: To improve
availability and transmission of data, we aim at developing a first prototype for
an electronic maternity record for Switzerland. METHODS: By analyzing the
documentation workflow during pregnancy, we determined a maternity record data
set. Further, we collected requirements towards a digital maternity record. As
data exchange format, the Swiss specific exchange format SMEEX (swiss medical
data exchange) was exploited. Feedback from 27 potential users was collected to
identify further improvements. RESULTS: The relevant data is extracted from the
primary care information system as SMEEX file, stored in a database and made
available in a web and a mobile application, developed as prototypes of an
electronic maternity record. CONCLUSION: The user confirmed the usefulness of the
system and provided multiple suggestions for an extension. An electronical
maternity record as developed in this work could be in future linked to the
electronic patient record.
PMID- 28508805
TI - Data Quality- and Master Data Management - A Hospital Case.
AB - Poor data quality prevents the analysis of data for decisions which are critical
for business. It also has a negative impact on business processes. Nevertheless
the maturity level of data quality- and master data management is still
insufficient in many organizations nowadays. This article discusses the
corresponding maturity of companies and a management cycle integrating data
quality- and master data management in a case dealing with benchmarking in
hospitals. In conclusion if data quality and master data are not properly
managed, structured data should not be acquired in the first place due to the
added expense and complexity.
PMID- 28508806
TI - Telemonitoring and Medical Care of Heart Failure Patients Supported by Left
Ventricular Assist Devices - The Medolution Project.
AB - Long-term survival after left ventricular assist device (LVAD) implantation in
heart failure patients is mainly determined by a sophisticated after-care.
Ambulatory visits only take place every 12 weeks. In case of life-threatening
complications (pump thrombosis, driveline infection) this might lead to delayed
diagnosis and delayed intervention. It is the intention of the international
project Medolution (Medical care evolution) to develop new approaches in order to
create best structures for telemonitoring of LVAD patients. In the very early
period of the project a questionnaire was sent to 180 LVAD patients to evaluate
the need and acceptance of telemonitoring. Thereafter, a graphical user interface
(GUI) mockup was developed as one of the first steps to improve the continuous
contact between the LVAD patient and the physician. As a final goal the
Medolution project aims to bundle all relevant informations from different data
sources into one platform in order to provide the physician a comprehensive
overview of a patient's situation. In the systems background a big data analysis
should run permanently and should try to detect abnormalities and correlations as
well. At crucial events, a notification system should inform the physician and
should provide the causing data via a decision support system. With this new
system we are expecting early detection and prevention of common and partially
life-threatening complications, less readmissions to the hospital, an increase in
quality of life for the patients and less costs for the health care system as
well.
PMID- 28508807
TI - New Service Excellence Model for eHealth and AAL Solutions - A Framework for
Continuous New Service Development.
AB - The development of eHealth and AAL (Ambient Assisted Living) services with the
aim to reduce the complexity of living environments for the elderly often does
not lead to the desired results on the market. The design of an eHealth/AAL
specific framework for continuous New Service Development is presented in this
paper. Our research addresses this challenge with a new Service Excellence Model
(SEM) and outlines the benefits of this specific approach. The research is based
on the data of the DALIA project (Assistant for DAily LIfe Activities at Home)
and the PenAAL project (Performance Measurement Index for AAL solutions), parts
of which the projects were the classification of relevant business dimensions and
the development of a related scoring tool for continuous benchmarking and
improvement.
PMID- 28508808
TI - Digital Media for Primary Health Care in Austria.
AB - Primary health care (PHC) is currently being improved in all developed
industries. The aim is to make healthcare more patient-centered and close to the
patient's place of residence. In addition to the organizational and
interdisciplinary reorientation, the use of digital media is increasingly being
emphasized. Through literature research and an online survey among Austrian
doctors and general practitioners, the current and future challenges for the use
of digital media in networked and regional primary health care were identified
and prioritized. It becomes clear that basic functions like documentation,
communication and coordination in the individual medical practice are at the
forefront. In the future it will be necessary to support regional and
interprofessional networking through digital media.
PMID- 28508809
TI - Health Information System in a Cloud Computing Context.
AB - Healthcare as a worldwide industry is experiencing a period of growth based on
health information technology. The capabilities of cloud systems make it as an
option to develop eHealth goals. The main objectives of the present study was to
evaluate the advantages and limitations of health information systems
implementation in a cloud-computing context that was conducted as a systematic
review in 2016. Science direct, Scopus, Web of science, IEEE, PubMed and Google
scholar were searched according study criteria. Among 308 articles initially
found, 21 articles were entered in the final analysis. All the studies had
considered cloud computing as a positive tool to help advance health technology,
but none had insisted too much on its limitations and threats. Electronic health
record systems have been mostly studied in the fields of implementation,
designing, and presentation of models and prototypes. According to this research,
the main advantages of cloud-based health information systems could be
categorized into the following groups: economic benefits and advantages of
information management. The main limitations of the implementation of cloud-based
health information systems could be categorized into the 4 groups of security,
legal, technical, and human restrictions. Compared to earlier studies, the
present research had the advantage of dealing with the issue of health
information systems in a cloud platform. The high frequency of studies conducted
on the implementation of cloud-based health information systems revealed health
industry interest in the application of this technology. Security was a subject
discussed in most studies due to health information sensitivity. In this
investigation, some mechanisms and solutions were discussed concerning the
mentioned systems, which would provide a suitable area for future scientific
research on this issue. The limitations and solutions discussed in this
systematic study would help healthcare managers and decision-makers take better
and more efficient advantages of this technology and make better planning to
adopt cloud-based health information systems.
PMID- 28508810
TI - Timed Up-and-Go Device for Unsupervised Functional Assessment of Elderly
Patients.
AB - Functional evaluation of elderly patients is one key component in a comprehensive
Geriatric Assessment. The increased workload and high costs associated to close
and continuous monitoring in clinical settings may be counterbalanced by the
application of ICT-supported remote follow-up. Although clinical parameters and
questionnaires can be supported with smartphones and smart gadgets, physical
performance trials pose a challenge for community-based approaches with
difficulties arising from setting up trials, the lack of guidance and
supervision. We developed an ultrasonic-based device to overcome all of these
barriers and enable elderly people to perform the Timed Up-and-Go test in an
autonomous and unsupervised setting. Moreover, we introduce an algorithm to
verify the successful performance of the test in order to increase the
reliability of the information provided.
PMID- 28508811
TI - Disease Monitoring Related Adherence and Its Association with Mortality in Lower
Austrian Diabetes Patients.
AB - BACKGROUND: Patient adherence is an important component of an efficient therapy.
For diabetes patients it may contribute to controlled glucose values and
reduction of adverse outcomes. OBJECTIVES: We aim to examine a potential
association of Lower Austrian diabetes patients' adherence concerning their
disease monitoring and mortality. METHODS: Using a retrospective cohort study
design, claims data of 55,873 diabetes patients were examined for regular HbA1c
lab tests that served as a proxy for monitoring related adherence. The cumulative
incidence of mortality was estimated in the total study population and separately
for different levels of adherence using the product-limit method. Mortality was
compared between the different levels of adherence by the log-rank test. RESULTS:
The cumulative incidence of mortality after one and two years was 4.2% and 8.7%.
Patients with low adherence had a significantly higher risk of mortality than
patients with high adherence (p < 0.001). Further results of a multivariable
analysis will be presented at the conference. CONCLUSION: According to our
preliminary univariate analysis, monitoring related adherence seems to be
substantially beneficial for diabetes patients in Lower Austria.
PMID- 28508812
TI - Comparison of Control Group Generating Methods.
AB - Retrospective studies suffer from drawbacks such as selection bias. As the
selection of the control group has a significant impact on the evaluation of the
results, it is very important to find the proper method to generate the most
appropriate control group. In this paper we suggest two nearest neighbors based
control group selection methods that aim to achieve good matching between the
individuals of case and control groups. The effectiveness of the proposed methods
is evaluated by runtime and accuracy tests and the results are compared to the
classical stratified sampling method.
PMID- 28508813
TI - Web and Mobile Based HIV Prevention and Intervention Programs Pros and Cons - A
Review.
AB - BACKGROUND: With the increasing growth of HIV positive people the use of
information and communication technologies (ICT) can play an important role in
controlling the spread of the AIDS. Web and Mobile are the new technologies that
young people take advantage from them. OBJECTIVES: In this study a review to
investigate the web and mobile based HIV prevention and intervention programs was
carried out. METHODS: A scoping review was conducted including PubMed, Science
direct, Web of Science and Proquest to find relevant sources that published in
2009 to 2016. To identify published, original research that reported the web and
mobile-based HIV prevention and intervention programs, an organized search was
conducted with the following search keywords in combination: HIV, AIDS, m-Health,
Mobile phone, Cell phone, Smartphone, Mobile health, internet, and web. RESULTS:
Using the employed strategies, 173 references retrieved. Searched articles were
compared based on their titles and abstracts. To identify duplicated articles,
the title and abstracts were considered and 101 duplicated references were
excluded. By going through the full text of related papers, 35 articles were
found to be more related to the questions of this paper from which 72 final
included. CONCLUSION: The advantages of web and mobile-based interventions
include the possibility to provide constancy in the delivery of an intervention,
impending low cost, and the ability to spread the intervention to an extensive
community. Online programs such as Chat room-based Education program, Web-based
therapeutic education system, and Online seek information can use for HIV/AIDS
prevention. To use of mobile for HIV/AIDS prevention and intervention, programs
including in: Health system focused applications, Population health focused
applications, and Health messaging can be used.
PMID- 28508814
TI - Plausibility of Individual Decisions from Random Forests in Clinical Predictive
Modelling Applications.
AB - BACKGROUND: Machine learning algorithms are a promising approach to help
physicians to deal with the ever increasing amount of data collected in
healthcare each day. However, interpretation of suggestions derived from
predictive models can be difficult. OBJECTIVES: The aim of this work was to
quantify the influence of a specific feature on an individual decision proposed
by a random forest (RF). METHODS: For each decision tree within the RF, the
influence of each feature on a specific decision (FID) was quantified. For each
feature, changes in outcome value due to the feature were summarized along the
path. Results from all the trees in the RF were statistically merged. The ratio
of FID to the respective feature's global importance was calculated (FIDrel).
RESULTS: Global feature importance, FID and FIDrel significantly differed,
depending on the individual input data. Therefore, we suggest to present the most
important features as determined for FID and for FIDrel, whenever results of a RF
are visualized. CONCLUSION: Feature influence on a specific decision can be
quantified in RFs. Further studies will be necessary to evaluate our approach in
a real world scenario.
PMID- 28508815
TI - Bluetooth Low Energy Peripheral Android Health App for Educational and
Interoperability Testing Purposes.
AB - Based on recent telemonitoring activities in Austria for enabling integrated
health care, the communication interfaces between personal health devices (e.g.
blood pressure monitor) and personal health gateway devices (e.g. smartphone,
routing received information to wide area networks) play an important role. In
order to ease testing of the Bluetooth Low Energy interface functionality of the
personal health gateway devices, a personal health device simulator was
developed. Based on specifications from the Bluetooth SIG a XML software test
configuration file structure is defined that declares the specific features of
the personal health devices simulated. Using this configuration file, different
scenarios are defined, e.g. send a single measurement result from a blood
pressure reading or sending multiple (historic) weight scale readings. The
simulator is intended to be used for educational purposes in lectures, where the
number of physical personal health devices can be reduced and learning can be
improved. It could be shown that this simulator assists the development process
of mHealth applications by reducing the time needed for development and testing.
PMID- 28508816
TI - Physicians' Use of Online Clinical Evidence in Mashhad University of Medical
Sciences, Iran.
AB - The Internet is an important source of medical information. It is expected that
the use of online sources will improve clinical decisions. This study aims to
evaluate online information seeking behavior of physicians of Mashhad University
of Medical Sciences on the use of online clinical evidence. A cross-sectional,
questionnaire-based study was carried out between November and December 2014 in
the five academic hospitals. A total of 252 physicians completed the
questionnaire. The majority of physicians (63.6 of specialists and 58.5% of
residents) had no internet access in their consultation and visit rooms. The
majority of physicians (77.8% of specialists and 80% of residents) respectively
used Google, as well as 67.5% specialists and 52.2% residents always used Medline
or PubMed, among electronic sources, to searching for information. The main
reasons for physicians' dissatisfaction with the Internet, as a source of health
information, were lack of access to medical sources owing to the non-targeted
filtering (61% specialists and 74.6% residents) and very slow connection of the
Internet (75.6% specialists and 83.1% residents). It is recommended that medical
informatics training programs should be incorporated, where physicians are
required to search for health information in the Internet.
PMID- 28508817
TI - Development of and Adherence to a Computer-Based Gamified Environment Designed to
Promote Health and Wellbeing in Older People with Mild Cognitive Impairment.
AB - BACKGROUND: The older population of Europe is increasing and there has been a
corresponding increase in long term care costs. This project sought to promote
active ageing by delivering tasks via a tablet computer to participants aged 65
80 with mild cognitive impairment. OBJECTIVES: An age-appropriate gamified
environment was developed and adherence to this solution was assessed through an
intervention. METHODS: The gamified environment was developed through focus
groups. Mixed methods were used in the intervention with the time spent engaging
with applications recorded supplemented by participant interviews to gauge
adherence. There were two groups of participants: one living in a retirement
village and the other living separately across a city. RESULTS: The retirement
village participants engaged in more than three times the number of game sessions
compared to the other group possibly because of different social arrangements
between the groups. CONCLUSION: A gamified environment can help older people
engage in computer-based applications. However, social community factors
influence adherence in a longer term intervention.
PMID- 28508818
TI - Biosignals, Standards and FHIR - The Way to Go?
AB - BACKGROUND: Standards have become available to share semantically encoded vital
parameters from medical devices, as required for example by personal healthcare
records. Standardised sharing of biosignal data largely remains open. OBJECTIVES:
The goal of this work is to explore available biosignal file format and data
exchange standards and profiles, and to conceptualise end-to-end solutions.
METHODS: The authors reviewed and discussed available biosignal file format
standards with other members of international standards development organisations
(SDOs). RESULTS: A raw concept for standards based acquisition, storage,
archiving and sharing of biosignals was developed. The GDF format may serve for
storing biosignals. Signals can then be shared using FHIR resources and may be
stored on FHIR servers or in DICOM archives, with DICOM waveforms as one possible
format. CONCLUSION: Currently a group of international SDOs (e.g. HL7, IHE,
DICOM, IEEE) is engaged in intensive discussions. This discussion extends
existing work that already was adopted by large implementer communities. The
concept presented here only reports the current status of the discussion in
Austria. The discussion will continue internationally, with results to be
expected over the coming years.
PMID- 28508819
TI - 128 SHADES OF RED: Objective Remote Assessment of Radiation Dermatitis by
Augmented Digital Skin Imaging.
AB - The purpose of our investigation was to develop a novel and state of the art
digital skin imaging method capable for remote monitoring and objective
assessment of Radiation Induced Dermatitis (RID). Therefore, radiation therapy
related side effects were assessed by medical experts according to Common
Terminology Criteria for Adverse Events (CTCAE) grade of severity in 20 female
breast cancer patients in a clinical trial over the treatment time frame of 25-28
radiation cycles, 50.0-50.4 Gy each. Furthermore the intensity of developed skin
erythema was documented by using conventional spectrophotometry plus digital skin
imaging. Thereby we could derive the Standardized Erythema Value (SEV), a novel
objective parameter, which in contrast to single parametric L* and a* delivers a
long dynamic measurement range for analyzing RID from bright to very dark skin
tones. Methodical superiority of the SEV could be proven over spectrophotometer
measurements in terms of a higher sensitivity and by enabling signal intensity
mapping in analyzed skin images. Our thereupon-derived patent enables novel
objective dermatologic eHealth applications in a broad range of medical and
industrial use by opening likewise the window for augmented dermatology. The
first of its kind system is now already further developed in form of the medical
device product Scarletred(r)Vision. It is available on the market for
primary usage in clinical trials and in medical routine.
PMID- 28508820
TI - Developing Interactive Plug-ins for tranSMART Using the SmartR Framework: The
Case of Survival Analysis.
AB - BACKGROUND: TranSMART has become an important and widely used platform for the
translational research. Included features for analysing data have significant
deficiencies concerning user interactivity with and export of the generated
results. SmartR, a plugin for tranSMART, promises to close this gap with its
interactive workflows. OBJECTIVES: Test with a proof of concept whether an own
SmartR workflow is possible. Improvement of the integrated survival analysis with
a self-build workflow, taking specific user requirements into account. METHODS:
Analysis of existing SmartR workflows to understand the underlying SmartR
architecture. Implementation of a SmartR workflow, which provides an improved
survival analysis. RESULTS: Extension of SmartR and thus tranSMART is possible
and could be successfully achieved with a prototype for survival analysis. The
framework still lacks some functionality, like binning of continuous variables,
and documentation. CONCLUSION: SmartR workflows are a good way for realising
interactive analysis, but the SmartR framework still needs further improvements
to become a full alternative to the already existing Rmodules.
PMID- 28508821
TI - Measuring the Negative Impact of Long Sitting Hours at High School Students Using
the Microsoft Kinect.
AB - This paper suggests the usage of the Microsoft Kinect to detect the onset of the
scoliosis at high school students due to incorrect sitting positions. The
measurement is done by measuring the overall posture in orthostatic position
using the Microsoft Kinect. During the measuring process several key points of
the human body are tracked like the hips and shoulders to form the postural data.
The test was done on 30 high school students who spend 6 to 7 hours per day in
the school benches. The postural data is statistically processed by IBM Watson's
Analytics. From the statistical analysis we have obtained that a prolonged
sitting position at such young ages affects in a negative way the spinal cord and
facilitates the appearance of malicious postures like scoliosis and lordosis.
PMID- 28508824
TI - From the editor.
PMID- 28508825
TI - ABCs of RhoGTPases indicating potential role as oncotargets.
AB - RhoGTPases also known as molecular switches represent a family of GTP-binding
proteins. They shuttle between "On" and "Off" states. In the "On" state, they
activate plethora of molecules. These proteins perform a wide variety of
functions involving cytoskeletal modeling, cell motility, migration, and mitosis.
Members of this family are referred as master regulators of many cellular
activities. Due to wide variety of portfolios attributed to RhoGTPases, their
misbehavior leads to initiation and also progression of metastatic cancers. Many
members of this family have been reported to be differentially regulated leading
to spread of malignant cells from one site to other. These wandering cells find a
comfortable site in accordance to Paget's soil and seed hypothesis and form
secondary lesions. Out of multiple members of this family, RhoA and RhoC are
important factors. RhoA is supposed to increase tumor proliferation when
overexpressed while RhoC is responsible for tumor initiation. We searched
publications on RhoGTPases, their functions and contribution in cancer
development and metastasis on World Wide Web and PubMed. This review focuses on
the role of Rac and Rho small GTPases in cell motility and granting the
opportunistic motile behavior of aggressive cancer cells. To condense knowledge
from existing literature about the roles played by these molecular switches,
their structural and functional ramifications are introduced in the beginning
followed by an account on their wrong behavior that leads to oncogenesis and
oncoprogression. This piece of work highlights members of RhoGTPases as viable
oncotargets.
PMID- 28508826
TI - Genomic aberrations in non- small cell lung cancer and their impact on treatment
outcome.
AB - The therapeutic options of nonsmall cell lung cancer (NSCLC) therapy has been
changed since the first discovery of activating epidermal growth factor receptor
(EGFR) mutations and the development of specific EGFR tyrosine kinase inhibitors,
which resulted in the evolution of "personalized medicine." There are a
considerable number of genomic aberrations in NSCLC serving as potential
predictive biomarkers and drug targets and still more. We summarized the
molecular pathways, potential targets, and possible impact on disease outcome in
NSCLC.
PMID- 28508827
TI - Multiple primary malignant neoplasms: A 10-year experience at a single
institution from Turkey.
AB - PURPOSE: The development of improved diagnostic techniques, increased survival,
and life expectancy of cancer patients have all contributed to the higher
frequency of multiple primary malignant neoplasms (MPMN). MPMN can be divided
into two main categories: Synchronous MPMN (sMPMN) and metachronous MPMN (mMPMN).
MATERIALS AND METHODS: 122 patients with MPMN analyzed retrospectively who were
admitted to the Radiation Oncology Department of Eskisehir Osmangazi University
Medical Faculty from January 2004 to December 2013. The patient characteristics
and relation with overall survival (OS) were examined. RESULTS: The overall
incidence of MPMN was found 1.2% in our institution. The median age was 59
(range: 29-80) years. Male:female ratio was 54.5:45.5%, and mMPMN:sMPMN ratio was
69.9:30.1%. The most common 3 cancers were head and neck (22%), breast (20%), and
gastrointestinal (20%) for first primary; and gastrointestinal (22%), lung (19%),
gynecologic tumors (15%) for second primary cancers, respectively. The median OS
in patients with sMPMN and mMPMN were 30 (3-105) and 91 (4-493) months. 2, 3, and
5 years OS of patients with sMPMN were 86%, 75%, 63%, and with mMPMN were 92%,
88%, 80%, respectively (P < 0.005). CONCLUSION: OS was found longer in female
patients with sMPMN (P < 0.05), and in all group with mMPMN (P < 0.005).
PMID- 28508828
TI - Evaluation of role of alpha-methyl acyl-coenzyme A racemase/P504S and high
molecular weight cytokeratin in diagnosing prostatic lesions.
AB - BACKGROUND: In recent years basal cell markers (high molecular weight cytokeratin
[HMWCK]) and prostate biomarker alpha-methyl acyl-coenzyme A racemase (AMACR)
have been used as adjuvant to morphology in diagnostically challenging cases with
a very high sensitivity and specificity. This has increased the diagnostic
accuracy of prostate cancer worldwide. MATERIALS AND METHODS: In this prospective
study, total of 50 cases including 37 cases of malignant lesions and 13 cases of
benign lesions of the prostate were taken. Tumor grade was determined according
to Gleason's grading system. AMACR and HMWCK expressions were determined by
immunohistochemical staining. The obtained results were analyzed and evaluated
using Chi-square statistical test (SPSS version 20). RESULTS: AMACR was not
expressed in any of the 13 cases of benign lesions of the prostate while in
malignant lesions of prostate it was expressed in 33 of 37 (89.18%) cases. All 4
(100%) cases of well-differentiated carcinoma were positive for AMACR expression.
21 of 25 (84%) moderately differentiated and all 10 (100%) cases of poorly
differentiated tumors were positive for AMACR. There was statistically
significant difference in expression of AMACR between benign and malignant
lesions of the prostate, indicated byP = 0.001. In benign lesions, HMWCK was
expressed in all the 13 (100%) cases while in malignant lesions of prostate it
was not expressed in any of the (0%) case. All 13 benign lesions were positive
for HMWCK only. AMACR expression was not seen in any of the benign lesion. Out of
37 malignant cases, 4 cases were negative for both, 33 cases were positive only
for AMACR, but no case was positive only for HMWCK. CONCLUSIONS: As an adjunct to
biopsy, AMACR and HMWCK have value for resolving diagnostically challenging
cases.
PMID- 28508829
TI - The association between rs1972820 and the risk of breast cancer in Isfahan
population.
AB - CONTEXT: A number of single nucleotide polymorphisms (SNPs) in ERBB4 gene have
been linked to increase the risk of breast cancer. However, no study has been
dedicated to analyze the significance of microRNA-related SNP rs1972820, located
in ERBB4 3'-untranslated region (UTR), in breast tumors. AIMS: Here, we
investigated the frequency and association between rs1972820 and breast cancer.
SUBJECTS AND METHODS: The rs1972820 genotypes in 182 samples were collected from
96 healthy people, and 86 breast cancer patients were determined using tetra
primer amplification refractory mutation system-polymerase chain reaction. The
frequency of genotypes was analyzed to find the association between rs1972820 and
breast cancer risk. STATISTICAL ANALYSIS USED: Conditional logistic regression,
odds ratios (ORs), the associated 95% confidence intervals (CIs), and Armitage's
test were used in this study. RESULTS: In silico analysis suggested that
rs1972820 located in the 3'UTR of ERBB4 gene affects the binding affinity of miR
3144-3p a potential oncomiRNA. Statistical analysis showed a significant
association between SNP rs1972820 G allele and reduced breast cancer risk, odds
ratio = 0.443 (95% CI: 0.196-0.998). CONCLUSIONS: rs1972820 SNP allele is
significantly associated with the reduced risk of breast cancer and could be
considered as a potential marker for breast cancer predisposition in population
of Isfahan.
PMID- 28508830
TI - Dosimetric verification of dose calculation algorithm in the lung during total
marrow irradiation using helical tomotherapy.
AB - INTRODUCTION: Treatment of proliferative diseases of the hematopoietic system
involves, in most cases, chemotherapy combined with radiation therapy, which is
intended to provide adequate immunosuppressant. Conventionally, total body
irradiation (TBI) was used; however, total marrow irradiation (TMI) performed
with helical tomotherapy (HT) has been proposed as an alternative, with the aim
of delivering the highest dose in the target area (skeleton bone). PURPOSE: The
purpose of this study is to evaluate the accuracy of the dose calculation
algorithm for the lung in TMI delivered with HT. METHODS: Thermoluminescent
detectors (TLD-100 Harshaw) were used to measure delivered doses. Doses were
calculated for 95 selected points in the central lung (53 TLDs) and near the rib
bones (42 TLDs) in the anthropomorphic phantom. A total of 12 Gy were delivered
(6 fractions of 2 Gy/fraction). RESULTS: HT-TMI technique reduces the dose
delivered to the lungs in a phantom model to levels that are much lower than
those reported for TBI delivered by a conventional linear accelerator. The mean
calculated lung dose was 5.6 Gy versus a mean measured dose of 5.7 +/- 2.4 Gy.
The maximum and minimum measured doses were, respectively, 11.3 Gy (chest wall)
and 2.8 Gy (central lung). At most of the 95 points, the measured dose was lower
than the calculated dose, with the largest differences observed in the region
located between the target volume and the adjacent lung tissue. The mean measured
dose was lower than the calculated dose in both primary locations: -3.7% in the
42 rib-adjacent detectors and -3.0% in the 53 central lung TLDs. CONCLUSION: Our
study has shown that the measured doses may be lower than those calculated by the
HT-TMI calculation algorithm. Although these differences between calculated and
measured doses are not clinically relevant, this finding merits further
investigation.
PMID- 28508831
TI - Dual phase cone-beam computed tomography in detecting <3 cm hepatocellular
carcinomas during transarterial chemoembolization.
AB - OBJECTIVE: The objective of this study was to evaluate the sensitivity of dual
phase cone-beam computed tomography (CBCT) in detecting small (<3 cm in diameter)
hepatocellular carcinoma (HCC) tumors during transarterial chemoembolization
(TACE). MATERIALS AND METHODS: Twenty-two consecutive patients with unresectable
small HCCs in whom TACE was performed were retrospectively evaluated. Contrast CT
or contrast magnetic resonance imaging (MRI) was performed in all patients within
1 month prior to the procedure. Dual phase CBCT was performed prior to TACE and
lipiodol-CBCT was performed after treatment. The sensitivity of dual phase CBCT
in detecting small HCCs was compared to hepatic angiography, contrast enhanced CT
and MRI. RESULTS: Seventy HCC tumors with sizes of P < 0.001). CONCLUSIONS: Dual
phase CBCT is significantly more sensitive than hepatic angiography, contrast
enhanced CT, and MRI in detecting smaller than 3 cm HCC tumors and can be a
helpful modality in making accurate planning for treatment of HCC.
PMID- 28508832
TI - Disease characteristics and treatment attributes of patients admitted to the
oncology ward of a tertiary care government hospital.
AB - BACKGROUND: The burden of oncology patients in the most developing countries
including India has witnessed a steady, progressive, and significant upward trend
attributed mainly to increased life span, availability of better imaging
modalities, increased awareness, and lifestyle and environmental changes. The
management of such patients in government setup often presents lots of challenges
such as advanced stage of presentation, existence of medical comorbid conditions,
scarcity of beds, and long multimodal treatment often complicated with therapy
induced toxicities. MATERIALS AND METHODS: A prospective study was undertaken in
a Radiation Oncology ward catering to male patients over 6-month duration in a
superspecialty hospital of defense services. The clinical, pathological, and
treatment-related attributes were recorded. Wherever possible, the clinical
course of stay, complications during admission, and the response to primary
management were studied. RESULTS: A total of 570 patients were admitted for 6
month duration. Of these patients, 240 were transferred in from other peripheral
service hospitals while the remaining were admitted directly from this hospital
or transferred from various wards of this hospital. The mean age of the patients
was 46.5 years. Most common histology was squamous cell carcinoma. The most
common site of primary was head and neck, followed closely by central nervous
system tumors and gastrointestinal tract. A total of 185 patients were fresh
cases admitted for workup and complete duration of definitive management (of
which 82 received concurrent chemoradiation), 280 patients were for follow-up, 70
patients were admitted briefly for supportive care during a while on
chemoradiation, and 15 patients were admitted for administrative reasons. Fifty
eight patients developed Grade II and onward therapy-induced hematological,
gastrointestinal, cutaneous complications, and 14 patients suffered from febrile
neutropenia. Thirty patients developed other significant complications warranting
cross-referrals to other specialists. One hundred and thirty patients underwent
more than one imaging modalities (contrast-enhanced computed tomography, magnetic
resonance imaging, bone scan, and positron emission tomography-computed
tomography). The duration of stay varied from 3 to 64 days, with an average
duration of 38 days. There were 18 deaths during the study period. CONCLUSION:
The course of hospitalization for oncology cases is often prolonged and
complicated by significant complications, warranting aggressive supportive care
by various concerned specialists. These patients often require multiple imaging
for primary and metastatic workup. There is a need for judicious selection of
patients meriting admission for optimum utilization of existing resources.
PMID- 28508833
TI - Radiation-induced non-targeted effect in vivo: Evaluation of cyclooygenase-2 and
endothelin-1 gene expression in rat heart tissues.
AB - AIM: In this study, we investigated expression levels of cyclooxygenase-2 (COX-2)
and endothelin-1 (ET-1) genes after pelvis and heart irradiation in a rat model.
These factors are involved in heart diseases (HDs). MATERIALS AND METHODS: We
used seven groups, including two groups of pelvic irradiation, two groups of
whole body irradiation, two groups of heart irradiation, and one control
nonirradiated group. Pelvis irradiations were conducted at a 2 cm * 2 cm in the
pelvis area. Irradiation condition conducted using 1.25 MeV cobalt-60 gamma-rays
(30 cGy/min). The changes at ET-1 and COX-2 gene expressions in heart tissue
after pelvis and heart irradiation were measured and compared to the control and
whole body irradiation groups at 24 h and 72 h after the exposure. RESULTS: In
heart irradiation groups, 3-fold up-regulation of both ET-1 and COX-2 was
observed. In pelvis irradiation groups, 3-fold up-regulation of ET-1 was seen,
but not significant changes in COX-2 gene expression have observed at distant
heart tissues after pelvis irradiation. CONCLUSION: This study reveals that
nontargeted effect induced by radiation may be considered as an important
phenomenon for induction of HD after radiotherapy.
PMID- 28508834
TI - A dosimetric analysis of cardiac dose with or without active breath coordinator
moderate deep inspiratory breath hold in left sided breast cancer radiotherapy.
AB - BACKGROUND AND AIM: Cardiac toxicity is a major concern for left breast
tangential field irradiation. The left ventricle and left anterior descending
(LAD) artery are suggested to be radiosensitive and radiation to these structures
leads to late lethal cardiotoxicity. Moderate deep inspiration breath hold
(mDIBH) during radiation treatment delivery helps in reducing the cardiac dose.
This study compares dosimetric parameters of heart with and without active breath
coordinator (ABC) mDIBH during tangential field breast cancer radiation. STUDY
TYPE: This is a dosimetric comparative study. MATERIALS AND METHODS: Forty-five
consecutive patients with left-sided breast cancer who underwent breast
conserving surgery and adjuvant tangential field and radiotherapy with ABC mDIBH
between November 2013 and September 2015 in our center were analyzed in this
study. The ABC device was used for respiratory control and patients who could
hold their breath for 20-30 s were considered for radiation with ABC mDIBH.
Simulation scans of both free breathing (FB) and ABC mDIBH were done. Tangent
field treatment plans with a dose prescription of 40 Gy/15 Fr were generated for
each patient, in both scans. Target coverage, dose to the heart, LAD, and the
left lung were documented with dose-volume histograms. RESULTS: Statistical
Package for the Social Sciences, version 20 software, was used for analysis and
the level of significance was set at P < 0.05. Mean heart dose was 308.5cGy with
FB and 159cGy with ABC (P < 0.0001). Mean dose to the LAD was reduced by 53.81%
(1320.64 cGy vs. 606.56 cGy, P < 0.001). Target coverage was equal in both the
plans. CONCLUSION: We report that the use of ABC mDIBH technique resulted in a
significant reduction in cardiac dose and hence can be considered as a promising
tool for cardiac sparing.
PMID- 28508835
TI - Beneficial influence of ellagic acid on biochemical indexes associated with
experimentally induced colon carcinogenesis.
AB - OBJECTIVE: To elucidate the key biochemical indexes associated with 1, 2
dimethylhydrazine (DMH)-induced colon carcinogenesis and the modulatory efficacy
of a dietary polyphenol, ellagic acid (EA). MATERIALS AND METHODS: Wistar rats
were chosen to study objective, and were divided into 4 groups; Group 1-control
rats; Group 2-rats received EA (60 mg/kg body weight/day, orally); rats in Group
3-induced with DMH (20 mg/kg body weight) subcutaneously for 15 weeks; DMH
induced Group 4 rats were initiated with EA treatment. We examined key citric
acid cycle enzymes such as isocitrate dehydrogenase, alpha-ketoglutarate
dehydrogenase, succinate dehydrogenase, malate dehydrogenase and the activities
of respiratory chain enzymes NADH dehydrogenase and Cytochrome-C-oxidase and
membrane-bound enzyme profiles (Na +/K + ATPase, Ca 2+ ATPase and Mg 2+ ATPase),
activities of lysosomal proteases such as beta-D-glucuronidase, beta
galactosidase and N-acety-beta-D-glucosaminidase and cellular thiols (oxidized
glutathione, protein thiols, and total thiols). RESULTS: It was found that
administration of DMH to rats decreased both mitochondrial and membrane-bound
enzymes activities, increased activities of lysosomal enzymes and further
modulates cellular thiols levels. Treatment with EA significantly restored the
mitochondrial and ATPases levels and further reduced lysosomal enzymes to near
normalcy thereby restoring harmful effects induced by DMH. CONCLUSION: EA
treatment was able to effectively restore the detrimental effects induced by DMH,
which proves the chemoprotective function of EA against DMH-induced experimental
colon carcinogenesis.
PMID- 28508836
TI - Tabulated square-shaped source model for linear accelerator electron beam
simulation.
AB - CONTEXT: Using this source model, the Monte Carlo (MC) computation becomes much
faster for electron beams. AIMS: The aim of this study was to present a source
model that makes linear accelerator (LINAC) electron beam geometry simulation
less complex. SETTINGS AND DESIGN: In this study, a tabulated square-shaped
source with transversal and axial distribution biasing and semi-Gaussian spectrum
was investigated. SUBJECTS AND METHODS: A low energy photon spectrum was added to
the semi-Gaussian beam to correct the bremsstrahlung X-ray contamination. After
running the MC code multiple times and optimizing all spectrums for four electron
energies in three different medical LINACs (Elekta, Siemens, and Varian), the
characteristics of a beam passing through a 10 cm * 10 cm applicator were
obtained. The percentage depth dose and dose profiles at two different depths
were measured and simulated. RESULTS: The maximum difference between simulated
and measured percentage of depth doses and dose profiles was 1.8% and 4%,
respectively. The low energy electron and photon spectrum and the Gaussian
spectrum peak energy and associated full width at half of maximum and transversal
distribution weightings were obtained for each electron beam. The proposed method
yielded a maximum computation time 702 times faster than a complete head
simulation. CONCLUSIONS: Our study demonstrates that there was an excellent
agreement between the results of our proposed model and measured data;
furthermore, an optimum calculation speed was achieved because there was no need
to define geometry and materials in the LINAC head.
PMID- 28508837
TI - Colorectal cancer presenting as bone metastasis.
AB - INTRODUCTION: Bone metastasis is a rare site of metastasis, seen in only 3.7-11%
of clinical cases. Isolated bone involvement has been reported very rarely in
literature. Moreover, the patients who have bone metastasis at presentation are
even rare. OBJECTIVES: To discuss the demographic characteristics,
carcinoembryonic antigen (CEA) levels, pattern of bone involvement, and their
correlation with survival in patients of colorectal cancer that have bone
metastasis at the time of presentation. MATERIALS AND METHODS: Retrospectively,
tumor registry was analyzed for the cases of colorectal cancer presenting with
bone metastasis between 2008 and 2013. Survival curves were generated by Kaplan
Meier method and analyzed using the log-rank test. RESULTS: Ten such patients
were identified (male:female = 7:3) of the total 410 patients. Median age was 41
years (22-50 years). All patients were Conclusions: In this study, the patients
of colorectal cancer presenting with bone metastasis were of male sex and younger
age. The factors that were associated with reduced survival were extraosseous and
liver involvement.
PMID- 28508838
TI - Randomized controlled Phase III study comparing hepatic arterial infusion with
systemic chemotherapy after curative resection for liver metastasis of colorectal
carcinoma: JFMC 29-0003.
AB - BACKGROUND: The feasibility and efficacy of adjuvant hepatic arterial infusion
(HAI) in preventing the development of liver metastases in patients with advanced
colon carcinoma have not been validated. The aim of this randomized controlled
study was to compare the feasibility of HAI and the protective effect against
liver metastasis after curative resection to those of systemic chemotherapy.
METHODS: Between July 2000 and June 2003, 91 patients were enrolled. Patients
were randomly assigned to receive 5-fluorouracil (5-FU) via continuous venous
infusion (CVI) or intra-hepatic arterial weekly high-dose 5-FU (WHF). The primary
endpoint was overall survival (OS). RESULTS: In the WHF group, the cumulative
failure rate of hepatic arterial catheterization was 16.7% at 6 months. The
occurrence of grade 3 adverse events was comparable between the groups. The 5
year OS rates were 59.0% in the CVI group and 34.9% in the WHF group (P = 0.164).
CVI tended to show a protective effect against liver metastasis regarding the 5
year liver-specific cumulative recurrence rate: CVI, 45.0% vs. WHF, 68.3%; P =
0.037). CONCLUSION: HAI therapy has a certain protective effect against liver
metastasis after curative resection in patients with colorectal cancer. However,
this therapy did not contribute to any marked improvement in their overall
survival.
PMID- 28508839
TI - Application of National Cancer Institute recommended terminology in breast
cytology.
AB - BACKGROUND: There is a lack of uniformity with regard to the reporting
terminology used in breast cytology by pathologists worldwide, resulting in
miscommunication of results among health-care providers. AIM: The present study
was aimed to assess the accuracy of fine-needle aspiration cytology (FNAC) in the
evaluation of breast lesions using the National Cancer Institute (NCI)
recommended terminology. MATERIALS AND METHODS: In this prospective study, a
total number of 523 breast FNACs were categorized according to the NCI
guidelines. Of these, 286 (54.7%) had histopathological follow-up, and their FNAC
diagnoses were compared. The sensitivity, specificity, positive predictive value
(PPV), and negative predictive value (NPV) along with 95% confidence interval
(95% CI) and accuracy of FNAC were calculated. RESULTS: Among 286 FNAC cases, 4
were unsatisfactory (C1), 188 were benign (C2), 11 were atypical, probably benign
(C3), 21 were suspicious, favor malignancy (C4), and 62 were malignant (C5). On
histopathological examination of categories C2 and C3 (total of 199 cases), 193
were confirmed as benign (true negative) and remaining 6 cases were turned out to
malignant (false negative). Among categories C4 and C5 (total of 83 cases), 81
were confirmed as malignant (true positive) and remaining 2 were turned out to be
benign (false positive). The sensitivity, specificity, PPV, NPV, and accuracy of
FNAC were 93.1% (95% CI, 88.2%-95%), 99% (95% CI, 96.8%-99.8%), 97.6% (95% CI,
92.5%-99.6%), 97% (95% CI, 94.9%-97.8%), and 97.2%, respectively. CONCLUSION: Our
study concluded that FNAC reporting using NCI guidelines highly correlated with
the histopathological diagnosis.
PMID- 28508840
TI - Comparison of beam hardening effect of physical and enhanced dynamic wedges at
bladder inhomogeneity using EBT3 film dosimeter.
AB - INTRODUCTION: Using physical wedges (PWs) to modify dose distribution and more
homogeneous target coverage is a well-established technique. However, there are
many problems with PWs known as beam hardening, which made them problematic. This
can be overcome by dynamic wedges which do not filter beam. Comparison of
physical properties of physical and enhanced dynamic wedges (EDWs) restricted to
homogeneous medium. Hence, the main aim of this study is to compare dosimetric
properties of physical and EDWs at bladder inhomogeneous phantom as a most common
case implementing wedges. MATERIALS AND METHODS: An inhomogeneous pelvic phantom
with homogeneities of uterus, femur, soft tissue, rectum, and bladder was
designed. Eclipse treatment planning system with the aim of bladder target was
used for calculations. All dose distributions were measured with EBT3 films.
RESULTS: Comparison between beam profiles of physical and EDWs at wedged and
nonwedged directions shows a greater difference at near inhomogeneous soft tissue
interface and also at heel side of wedges. CONCLUSION: Little difference observed
between dose distribution of physical and EDWs shows neglectable effect of beam
hardening produced by PW compared to EDW at inhomogeneous medium. Furthermore,
EBT3 films present good feature to measure dose distributions at EDW fields.
PMID- 28508841
TI - Morbidity of central compartment clearance: Comparison of lesser versus complete
clearance in patients with thyroid cancer.
AB - BACKGROUND: Extent of central compartment neck dissection (CCND) in thyroid
cancers has been a debate because of associated morbidity. There have been
attempts to reduce the extent of surgery in an attempt to decrease morbidity.
PATIENTS AND METHODS: We analyzed the morbidity of CCND from our prospectively
maintained surgical morbidity database. CCND was divided into bilateral complete
clearance (BCC) and less than complete clearance (LCC). LCC was performed for
clinicoradiologically node negative patients. Rates of hypocalcemia and recurrent
laryngeal nerve (RLN) palsy rates were compared for LCC versus BCC. We also
classified procedures performed in the central neck according to the extent of
dissection. RESULTS: Of 153 evaluable patients, BCC was performed in 43.8% and
LCC in 56.2%. Rate of postoperative hypocalcemia was 40.2% in BCC group versus
17.4% in LCC group. We had an overall RLN palsy rate of 7.4%. There was no
significant difference in RLN palsy rates between the groups. CONCLUSION: Lesser
extent of dissection in central compartment reduces postoperative hypocalcemia
but has no influence on RLN palsy rates.
PMID- 28508842
TI - A3 adenosine receptor agonist induce G1 cell cycle arrest via Cyclin D and cyclin
dependent kinase 4 pathways in OVCAR-3 and Caov-4 cell lines.
AB - AIM OF THE STUDY: The cell cycle, a vital process that involves in cells' growth
and division, lies at the heart of cancer. It has been shown that IB-MECA, an A3
adenosine receptor agonist inhibits the proliferation of cancer cells by inducing
cell cycle arrest in several tumors. In this study, we evaluated the role of IB
MECA inhibition in cell cycle progression in ovarian cancer cells. MATERIALS AND
METHODS: Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide assay in Caov-4 and OVCAR-3. Analysis of cell cycle
distribution was carried out by flow cytometry. To determine the mechanisms of IB
MECA-mediated induction of cell cycle arrest, the expression of cell cycle
regulatory proteins Cyclin D1 and cyclin-dependent kinase 4 (CDK4) was evaluated.
RESULTS: Our results showed that IB-MECA significantly reduced cell viability in
a dose-dependent manner. Moreover, our results indicated that a low concentration
of IB-MECA induced G1 cell cycle arrest. Reduction of Cyclin D1 and CDK4 protein
levels was also observed after treating cancer cells with IB-MECA. CONCLUSION:
This study demonstrated that IB-MECA induces G1 phase cell cycle arrest through
Cyclin D1/CDK4-mediated pathway in ovarian cancer cells.
PMID- 28508843
TI - Acoustic analysis of voice in nonlaryngeal head and neck cancer patients post
chemoradiotherapy.
AB - BACKGROUND: Concurrent chemoradiotherapy (CCRT) used for definitive management of
locally advanced head and neck squamous cell carcinoma (HNSCC) allows organ
preservation at the cost of preservation of function. Vocal cords, being within
the field of irradiation, undergo acute and chronic changes which adversely
impacts the patients' voice. AIMS: To assess the acute changes in the acoustic
characteristics of voice post-CCRT in patients with nonlaryngeal HNSCC. MATERIALS
AND METHODS: Thirty patients with HNSCC treated with CCRT, a total dose of 66-70
Gy/33-35 fractions at five fractions/week, with weekly cisplatin. Acoustic
analysis (AA) and laryngoscopic examination performed at baseline, 6 weeks, and 3
months post-CCRT. Statistical analysis of the parameters using ANOVA and
Student's t-test was performed. RESULTS: Of the thirty patients, 26 patients
completed CCRT. At 6 weeks post-CCRT, among 14/26 patients, most (11/14 [78.57%])
developed Grade III toxicity. On AA, both increase and decrease in mean F0 from
baseline was observed. An increase (P < 0.05) in each, i.e., jitter, shimmer, and
noise to harmonics ratio (NHR) were recorded. At 3 months post-CCRT, among 8/14
available, most (6/8 [75%]) showed Grade II toxicity. The mean F0 reduced for
both genders; jitter and shimmer, and NHR values maintained an increase (P >
0.05). CONCLUSIONS: Periodic AA allows quantification of voice changes and
mapping of vocal toxicity induced by CCRT.
PMID- 28508844
TI - Evaluation of the effect of temperature variation on response of PRESAGE(r)
dosimeter.
AB - INTRODUCTION: Many factors, such as PRESAGE (r) composition, dose rate, energy,
and type of radiation, temperature, etc., may effect on PRESAGE (r) dosimeter
response. The aim of this study was investigating the effect of temperature
variation on response of PRESAGE (r) solid dosimeter. MATERIALS AND METHODS: In
this study, a PRESAGE (r) solid detector was fabricated. Ninety-four percent
weight polyurethane, 5% weight carbon tetrachloride, and 1% weight leucomalachite
green were used. Radiological and physical characteristics of PRESAGEs (r), such
as mass density, electron density, and effective number atomic were obtained and
compared with water. Response of PRESAGE (r) dosimeter in temperatures -4, 10,
25, 35, 45, 55, 65, 75, 85, and 90 degrees C was evaluated. In addition, the
absorption peak at various temperatures was investigated. RESULTS: The results
showed that the absorption peak at different temperatures was in the range of 630
635 nm. For temperatures below 75 degrees C, the results indicated that
temperature variation has no effect on the response of PRESAGE (r) dosimeter
whereas at the temperatures> 75 degrees C, temperature variation has an effect on
PRESAGE (r) dosimeter response. CONCLUSION: The finding showed that temperature
changes have not impact on the absorption peak. In addition, the results related
to the effect of temperature variation on the response of PRESAGE (r) dosimeter
showed that in the range of clinical applications (temperatures below 75 degrees
C), temperature variation has no effect on PRESAGE (r) dosimeter response.
PMID- 28508845
TI - Dosimetric comparison of head and neck cancer patients planned with multivendor
volumetric modulated arc therapy technology.
AB - AIM: Purpose of this study is to dosimetrically compare head and neck (H and N)
cancer patients planned with multivendor volumetric modulated arc therapy (VMAT)
technology. VMAT treatment planning can be done using biological (treatment
planning system [TPSB]: Monaco) or physical (TPSP: Eclipse)-based cost function
optimization techniques. Planning and dosimetric comparisons were done in both
techniques for H and N cases. MATERIALS AND METHODS: Twenty H and N patients were
retrospectively selected for this study. VMAT plans were generated using TPSP
(V11.0) and TPSB (V3.0) TPS. A total dose of 66 Gy (planning target volume 1
[PTV1]) and 60 Gy (PTV2) were prescribed to primary and nodal target volumes.
Clinical planning objectives were achieved by both the optimization techniques.
Dosimetric parameters were calculated for PTVs, and quantitative analyses were
performed for critical organs. Monitor units were compared between two TPSs, and
gamma analysis was performed between I'matriXX measured and TPS calculated.
RESULTS: Clinically, acceptable VMAT plans showed comparable dose distributions
between TPSB and TPSP optimization techniques. Comparison of mean dose,
homogeneity index, and conformity index for PTV1 showed no statistical difference
(P - 0.922, 0.096, and 0.097); however, in PTV2 statistically significant
difference was observed (P - 0.024, 0.008, and 0.002) between TPSB and TPSP. TPSB
optimization showed statistically significant superiority for spinal cord and
brainstem (D1% P - 0.0078, 0.00002) whereas improved parotid sparing was observed
in TPSP optimization (mean dose P - 0.00205). Gamma analysis illustrated that
both systems could produce clinically deliverable plans. CONCLUSION: VMAT plans
by TPSP and TPSB offered clinically acceptable dose distributions. TPSB-based
optimization showed enhanced sparing of serial organs whereas TPSP-based
optimization showed superior sparing of parallel organs.
PMID- 28508846
TI - Assessment of three-dimensional setup errors in image-guided pelvic radiotherapy
for uterine and cervical cancer using kilovoltage cone-beam computed tomography
and its effect on planning target volume margins.
AB - PURPOSE: To achieve the best possible therapeutic ratio using high-precision
techniques (image-guided radiation therapy/volumetric modulated arc therapy
[IGRT/VMAT]) of external beam radiation therapy in cases of carcinoma cervix
using kilovoltage cone-beam computed tomography (kV-CBCT). MATERIALS AND METHODS:
One hundred and five patients of gynecological malignancies who were treated with
IGRT (IGRT/VMAT) were included in the study. CBCT was done once a week for
intensity-modulated radiation therapy and daily in IGRT/VMAT. These images were
registered with the planning CT scan images and translational errors were applied
and recorded. In all, 2078 CBCT images were studied. The margins of planning
target volume were calculated from the variations in the setup. RESULTS: The
setup variation was 5.8, 10.3, and 5.6 mm in anteroposterior, superoinferior, and
mediolateral direction. This allowed adequate dose delivery to the clinical
target volume and the sparing of organ at risks. CONCLUSION: Daily kV-CBCT is a
satisfactory method of accurate patient positioning in treating gynecological
cancers with high-precision techniques. This resulted in avoiding geographic
miss.
PMID- 28508847
TI - Role of aquaporins in oral cancer.
AB - Aquaporins (AQP) are the membrane proteins involved in the transport of water and
some neutral solutes. Thirteen types of AQP are identified in various human
tissues. The expression of AQP's has been studied in various tumors among one is
oral cancer. These molecules are involved in cell proliferation, migration, and
metastasis. AQP target inhibitors act directly or indirectly through focal
adhesion kinase-mitogen-activated protein kinase signaling pathway and shown
promising results along with anti-cancer drugs. However, further researches were
required to verify the efficiency and safety of these AQPs-target inhibitors in
clinical therapy.
PMID- 28508848
TI - Recurrent osteosarcoma with calcified liver metastases: Uncommon development of a
common disease.
AB - Osteosarcoma is the commonest primary malignant bone tumor. Since bones lack a
lymphatic system, metastatic spread in these tumors is exclusively hematogenous,
the commonest sites being lungs and bone. We report a case of osteosarcoma
humerus which recurred locally after primary therapy consisting of neoadjuvant
chemotherapy and limb salvage surgery, who developed calcified liver metastases
in addition to local and pulmonary relapse. Liver, though a common site of
hematogenous spread in most solid tumors, has rarely been reported to be involved
in metastatic osteosarcomas.
PMID- 28508849
TI - Coexistence of hard palate carcinoma with tuberculosis: A rarity.
AB - Coexistence of tuberculosis (TB) and palatal malignancy is a rare phenomenon and
it has never been reported. Here, we present a case of hard palate carcinoma with
TB in a 60-year-old male patient who was successfully managed by three pronged
approaches by combining antitubercular therapy with chemotherapy and
radiotherapy.
PMID- 28508850
TI - Anaplastic hemangiopericytoma of eyelid: An unusual location.
AB - Hemangiopericytomas (HPCs) are rare soft tissue tumors. The eyelid is a very
uncommon site for these tumors, and an anaplastic variant of HPC in the eyelid
has not been reported before. A 44-year-old male presented with complaints of
slowly progressive, painless swelling on the inner aspect of the left upper
eyelid for 9 months. He underwent local excision of the swelling and
histopathology revealed a WHO Grade III anaplastic HPC. Whole body 18 F
fluorodeoxyglucose positron emission tomography-computed tomography done
postoperatively did not show any evidence of local or distant disease. The
patient was planned for adjuvant radiotherapy of 60 Gy in 30 fractions over 6
weeks in view of high grade of histopathology and doubtful margins. He is disease
free at the time of the last follow-up. To the best of our knowledge, this is the
first case of anaplastic HPC of eyelid being reported in English literature.
PMID- 28508851
TI - Sialadenoma papilliferum: A rare case report and review of literature.
AB - Sialadenoma papilliferum (SP) classified under the ductal papillomas by the WHO
is a rare benign tumor of minor salivary glands. It is a rare lesion of salivary
glands predominantly affecting the minor glands. It has characteristic exophytic
and endophytic clinical growth pattern. Histopathologically, it is characterized
by papillary projections supported by fibrovascular connective tissue core and
infiltrated with mixed inflammatory cells. The ductal lining epithelium of double
layered cells of luminal layer of tall columnar cells and a basilar layer of
small cuboidal cells shows additional papillary projections into the lumen. We
report a case of SP of mid palate.
PMID- 28508852
TI - Transcoelomic spread and ovarian seeding during ovulation: A possible
pathogenesis of Krukenberg tumor.
PMID- 28508853
TI - Accelerated fraction radiation therapy versus concurrent chemoradiation therapy
for locally advanced head and neck cancers: Is there evidence of equivalent
effect?
PMID- 28508854
TI - Erratum: Effects of food insecurity on the women esophageal cancer in the Zanjan
Province.
AB - This corrects the article DOI: 10.4103/0973-1482.206303.].
PMID- 28508855
TI - Retraction: Evaluation and identification of factors related to KRAS and BRAF
gene mutations in colorectal cancer: A meta analysis.
AB - [This corrects the article DOI: 10.4103/0973-1482.206304.].
PMID- 28508856
TI - Association between carotid plaque score and microvascular complications of type
2 diabetes.
AB - INTRODUCTION: According to the "common soil" hypothesis, diabetic microangiopathy
and macroangiopathy have a similar pathophysiological background. It has been
well documented that carotid artery atherosclerosis in patients with type 2
diabetes is associated with cardiovascular complications; however, it remains
unclear whether there is a similar association for microvascular complications.
OBJECTIVES: We investigated whether the carotid plaque score and the carotid
intima-media thickness (IMT) are associated with macroangiopathic and
microangiopathic complications of type 2 diabetes. PATIENTS AND METHODS: We
enrolled patients with type 2 diabetes and microvascular complications or overt
macroangiopathy. A B-mode carotid ultrasound was performed in all participants,
and anthropometric parameters, hemoglobin A1c (HbA1c) levels, lipid profile, and
smoking status were assessed. RESULTS: The study included 73 patients (mean [SD]
age, 63.6 [7.5] years; 36 men [49%]). The mean (SD) diabetes duration was 11.7
(8.1) years. Microvascular complications were observed in 32 patients (43.8%),
and overt macroangiopathy, in 42 (57.5%). Hypertension was reported for 60
patients (82%); dyslipidemia, for 56 (77%); obesity, for 37 (51%); and smoking,
for 10 (14%). A multivariate regression analysis showed that the carotid plaque
score, but not carotid IMT, was significantly associated with dyslipidemia (P =
0.03) and microangiopathy (P = 0.01). CONCLUSIONS: Our results indicate that,
unlike carotid IMT, the carotid plaque score is independently associated with
microangiopathic complications in type 2 diabetes. Patients with a high plaque
score should receive special care and the most intensive treatment to stop
progression of these complications.
PMID- 28508857
TI - Controlling photophysical properties of ultrasmall conjugated polymer
nanoparticles through polymer chain packing.
AB - Applications of conjugated polymer nanoparticles (Pdots) for imaging and sensing
depend on their size, fluorescence brightness and intraparticle energy transfer.
The molecular design of conjugated polymers (CPs) has been the main focus of the
development of Pdots. Here we demonstrate that proper control of the physical
interactions between the chains is as critical as the molecular design. The
unique design of twisted CPs and fine-tuning of the reprecipitation conditions
allow us to fabricate ultrasmall (3.0-4.5 nm) Pdots with excellent
photostability. Extensive photophysical and structural characterization reveals
the essential role played by the packing of the polymer chains in the particles
in the intraparticle spatial alignment of the emitting sites, which regulate the
fluorescence brightness and the intraparticle energy migration efficiency. Our
findings enhance understanding of the relationship between chain interactions and
the photophysical properties of CP nanomaterials, providing a framework for
designing and fabricating functional Pdots for imaging applications.
PMID- 28508858
TI - Onset of meso-scale turbulence in active nematics.
AB - Meso-scale turbulence is an innate phenomenon, distinct from inertial turbulence,
that spontaneously occurs at low Reynolds number in fluidized biological systems.
This spatiotemporal disordered flow radically changes nutrient and molecular
transport in living fluids and can strongly affect the collective behaviour in
prominent biological processes, including biofilm formation, morphogenesis and
cancer invasion. Despite its crucial role in such physiological processes,
understanding meso-scale turbulence and any relation to classical inertial
turbulence remains obscure. Here we show how the motion of active matter along a
micro-channel transitions to meso-scale turbulence through the evolution of
locally disordered patches (active puffs) from an ordered vortex-lattice flow
state. We demonstrate that the stationary critical exponents of this transition
to meso-scale turbulence in a channel coincide with the directed percolation
universality class. This finding bridges our understanding of the onset of low
Reynolds-number meso-scale turbulence and traditional scale-invariant turbulence
in confinement.
PMID- 28508860
TI - Circular RNAs: Coding or noncoding?
AB - Circular RNAs (circRNAs) were only recently discovered as a new class of
noncoding RNAs, functionally still largely uncharacterized. Three publications
that appeared concurrently in Cell Research and Molecular Cell provide initial
evidence for certain endogenous circRNAs coding for proteins.
PMID- 28508861
TI - Erratum: Biotemplating pores with size and shape diversity for Li-oxygen Battery
Cathodes.
PMID- 28508859
TI - Plastic roles of pericytes in the blood-retinal barrier.
AB - The blood-retinal barrier (BRB) consists of tightly interconnected capillary
endothelial cells covered with pericytes and glia, but the role of the pericytes
in BRB regulation is not fully understood. Here, we show that platelet-derived
growth factor (PDGF)-B/PDGF receptor beta (PDGFRbeta) signalling is critical in
formation and maturation of BRB through active recruitment of pericytes onto
growing retinal vessels. Impaired pericyte recruitment to the vessels shows
multiple vascular hallmarks of diabetic retinopathy (DR) due to BRB disruption.
However, PDGF-B/PDGFRbeta signalling is expendable for maintaining BRB integrity
in adult mice. Although selective pericyte loss in stable adult retinal vessels
surprisingly does not cause BRB disintegration, it sensitizes retinal vascular
endothelial cells (ECs) to VEGF-A, leading to upregulation of angiopoietin-2
(Ang2) in ECs through FOXO1 activation and triggering a positive feedback that
resembles the pathogenesis of DR. Accordingly, either blocking Ang2 or activating
Tie2 greatly attenuates BRB breakdown, suggesting potential therapeutic
approaches to reduce retinal damages upon DR progression.
PMID- 28508862
TI - Nanogenerator-based dual-functional and self-powered thin patch loudspeaker or
microphone for flexible electronics.
AB - Ferroelectret nanogenerators were recently introduced as a promising alternative
technology for harvesting kinetic energy. Here we report the device's intrinsic
properties that allow for the bidirectional conversion of energy between
electrical and mechanical domains; thus extending its potential use in wearable
electronics beyond the power generation realm. This electromechanical coupling,
combined with their flexibility and thin film-like form, bestows dual-functional
transducing capabilities to the device that are used in this work to demonstrate
its use as a thin, wearable and self-powered loudspeaker or microphone patch. To
determine the device's performance and applicability, sound pressure level is
characterized in both space and frequency domains for three different
configurations. The confirmed device's high performance is further validated
through its integration in three different systems: a music-playing flag, a sound
recording film and a flexible microphone for security applications.
PMID- 28508863
TI - Anthropogenic iron oxide aerosols enhance atmospheric heating.
AB - Combustion-induced carbonaceous aerosols, particularly black carbon (BC) and
brown carbon (BrC), have been largely considered as the only significant
anthropogenic contributors to shortwave atmospheric heating. Natural iron oxide
(FeOx) has been recognized as an important contributor, but the potential
contribution of anthropogenic FeOx is unknown. In this study, we quantify the
abundance of FeOx over East Asia through aircraft measurements using a modified
single-particle soot photometer. The majority of airborne FeOx particles in the
continental outflows are of anthropogenic origin in the form of aggregated
magnetite nanoparticles. The shortwave absorbing powers (Pabs) attributable to
FeOx and to BC are calculated on the basis of their size-resolved mass
concentrations and the mean Pabs(FeOx)/Pabs(BC) ratio in the continental outflows
is estimated to be at least 4-7%. We demonstrate that in addition to carbonaceous
aerosols the aggregate of magnetite nanoparticles is a significant anthropogenic
contributor to shortwave atmospheric heating.
PMID- 28508864
TI - Power generator driven by Maxwell's demon.
AB - Maxwell's demon is an imaginary entity that reduces the entropy of a system and
generates free energy in the system. About 150 years after its proposal,
theoretical studies explained the physical validity of Maxwell's demon in the
context of information thermodynamics, and there have been successful
experimental demonstrations of energy generation by the demon. The demon's next
task is to convert the generated free energy to work that acts on the
surroundings. Here, we demonstrate that Maxwell's demon can generate and output
electric current and power with individual randomly moving electrons in small
transistors. Real-time monitoring of electron motion shows that two transistors
functioning as gates that control an electron's trajectory so that an electron
moves directionally. A numerical calculation reveals that power generation is
increased by miniaturizing the room in which the electrons are partitioned. These
results suggest that evolving transistor-miniaturization technology can increase
the demon's power output.
PMID- 28508866
TI - Tuning colloidal quantum dot band edge positions through solution-phase surface
chemistry modification.
AB - Band edge positions of semiconductors determine their functionality in many
optoelectronic applications such as photovoltaics, photoelectrochemical cells and
light emitting diodes. Here we show that band edge positions of lead sulfide
(PbS) colloidal semiconductor nanocrystals, specifically quantum dots (QDs), can
be tuned over 2.0 eV through surface chemistry modification. We achieved this
remarkable control through the development of simple, robust and scalable
solution-phase ligand exchange methods, which completely replace native ligands
with functionalized cinnamate ligands, allowing for well-defined, highly tunable
chemical systems. By combining experiments and ab initio simulations, we
establish clear relationships between QD surface chemistry and the band edge
positions of ligand/QD hybrid systems. We find that in addition to ligand dipole,
inter-QD ligand shell inter-digitization contributes to the band edge shifts. We
expect that our established relationships and principles can help guide future
optimization of functional organic/inorganic hybrid nanostructures for diverse
optoelectronic applications.
PMID- 28508865
TI - An allosteric site in the T-cell receptor Cbeta domain plays a critical
signalling role.
AB - The molecular mechanism through which the interaction of a clonotypic alphabeta T
cell receptor (TCR) with a peptide-loaded major histocompatibility complex
(p/MHC) leads to T-cell activation is not yet fully understood. Here we exploit a
high-affinity TCR (B4.2.3) to examine the structural changes that accompany
binding to its p/MHC ligand (P18-I10/H2-Dd). In addition to conformational
changes in complementarity-determining regions (CDRs) of the TCR seen in
comparison of unliganded and bound X-ray structures, NMR characterization of the
TCR beta-chain dynamics reveals significant chemical shift effects in sites
removed from the MHC-binding site. Remodelling of electrostatic interactions near
the Cbeta H3 helix at the membrane-proximal face of the TCR, a region implicated
in interactions with the CD3 co-receptor, suggests a possible role for an
allosteric mechanism in TCR signalling. The contribution of these TCR residues to
signal transduction is supported by mutagenesis and T-cell functional assays.
PMID- 28508869
TI - Multidisciplinary Team-Based Approaches to IBD Management: How Might "One-Stop
Shopping" Work for Complex IBD Care?
PMID- 28508867
TI - Bloating and Abdominal Distension: Old Misconceptions and Current Knowledge.
AB - Bloating, as a symptom and abdominal distension, as a sign, are both common
functional-type complaints and challenging to manage effectively. Individual
patients may weight differently the impact of bloating and distension on their
well-being. Complaints may range from chronic highly distressing pain to simply
annoying and unfashionable protrusion of the abdomen. To avoid mishaps, organic
bloating, and distension should always be considered first and appropriated
assessed. Functional bloating and distension often present in association with
other manifestations of irritable bowel syndrome or functional dyspepsia and in
that context patients tend to regard them as most troublesome. A mechanism-based
management bloating and distension should be ideal but elucidating key
operational mechanisms in individual patients is not always feasible. Some clues
may be gathered through a detailed dietary history, by assessing bowel movement
frequency and stool consistency and special imaging technique to measure
abdominal shape during episodes of distension. In severe, protracted cases it may
be appropriate to refer the patient to a specialized center where motility,
visceral sensitivity, and abdominal muscle activity in response to intraluminal
stimuli may be measured. Therapeutic resources focussed upon presumed or
demonstrated pathogenetic mechanism include dietary modification, microbiome
modulation, promoting gas evacuation, attenuating visceral perception, and
controlling abdominal wall muscle activity via biofeedback.
PMID- 28508868
TI - Influence of Age and Eosinophilic Esophagitis on Esophageal Distensibility in a
Pediatric Cohort.
AB - OBJECTIVES: Sequelae of eosinophilic esophagitis (EoE) include food impaction and
esophageal stricture. Duration of inflammation is a predicted risk factor;
however, complications remain unpredictable. Studies using the functional lumen
imaging probe (FLIP) have demonstrated decreased distensibility of the esophagus
in adult patients with EoE. As the impact of inflammation on the developing
esophagus is unknown, we investigated esophageal distensibility in a pediatric
cohort to determine the effect of age, ongoing inflammation, and fibrotic
features on distensibility. METHODS: We conducted a prospective observational
study at two tertiary pediatric institutions. Subjects underwent FLIP evaluation
during endoscopy to determine distensibility of the esophagus. During stepwise
distension, simultaneous intrabag pressure and 16 channels of cross-sectional
areas were measured. The minimal diameter at maximal esophageal distention at an
intrabag pressure of 40 mm Hg was identified. Distensibility was compared between
EoE and non-EoE subjects and between clinical variables within the EoE cohort.
Potential confounding variables were identified. RESULTS: Forty-four non-EoE and
88 EoE subjects aged 3-18 years were evaluated. Age positively correlated with
esophageal distensibility in the non-EoE cohort, but this trend was not observed
in the EoE population. Subjects with EoE had reduced distensibility even after
adjusting for age. Active inflammation (eosinophils >15 eos/high-power field),
histological lamina propria fibrosis, and various features of a fibrotic
phenotype (stricture, food impaction, circumferential rings on endoscopy) were
associated with decreased distensibility within the EoE cohort. FLIP was safe,
feasible, and well tolerated. CONCLUSIONS: These findings suggest that remodeling
occurs in the pediatric EoE population, warranting early diagnosis and initiation
of therapy prior to the onset of disease complications.
PMID- 28508870
TI - Injection and controlled motion of conducting domain walls in improper
ferroelectric Cu-Cl boracite.
AB - Ferroelectric domain walls constitute a completely new class of sheet-like
functional material. Moreover, since domain walls are generally writable,
erasable and mobile, they could be useful in functionally agile devices: for
example, creating and moving conducting walls could make or break electrical
connections in new forms of reconfigurable nanocircuitry. However, significant
challenges exist: site-specific injection and annihilation of planar walls, which
show robust conductivity, has not been easy to achieve. Here, we report the
observation, mechanical writing and controlled movement of charged conducting
domain walls in the improper-ferroelectric Cu3B7O13Cl. Walls are straight, tens
of microns long and exist as a consequence of elastic compatibility conditions
between specific domain pairs. We show that site-specific injection of conducting
walls of up to hundreds of microns in length can be achieved through locally
applied point-stress and, once created, that they can be moved and repositioned
using applied electric fields.
PMID- 28508871
TI - Non-cell-autonomous activation of IL-6/STAT3 signaling mediates FGF19-driven
hepatocarcinogenesis.
AB - Hepatocellular carcinoma (HCC), a primary malignancy of the liver, is the second
leading cause of cancer mortality worldwide. Fibroblast Growth Factor 19 (FGF19)
is one of the most frequently amplified genes in HCC patients. Moreover, mice
expressing an FGF19 transgene have been shown to develop HCC. However, the
downstream signalling pathways that mediate FGF19-dependent tumorigenesis remain
to be deciphered. Here we show that FGF19 triggers a previously unsuspected, non
cell-autonomous program to activate STAT3 signalling in hepatocytes through IL-6
produced in the liver microenvironment. We show that the hepatocyte-specific
deletion of Stat3, genetic ablation of Il6, treatment with a neutralizing anti-IL
6 antibody or administration of a small-molecule JAK inhibitor, abolishes FGF19
induced tumorigenesis, while the regulatory functions of FGF19 in bile acid,
glucose and energy metabolism remain intact. Collectively, these data reveal a
key role for the IL-6/STAT3 axis in potentiating FGF19-driven HCC in mice, a
finding which may have translational relevance in HCC pathogenesis.
PMID- 28508874
TI - Lung cancer: Tracing tumour evolution.
PMID- 28508872
TI - Actin stress fiber organization promotes cell stiffening and proliferation of pre
invasive breast cancer cells.
AB - Studies of the role of actin in tumour progression have highlighted its key
contribution in cell softening associated with cell invasion. Here, using a human
breast cell line with conditional Src induction, we demonstrate that cells
undergo a stiffening state prior to acquiring malignant features. This state is
characterized by the transient accumulation of stress fibres and upregulation of
Ena/VASP-like (EVL). EVL, in turn, organizes stress fibres leading to transient
cell stiffening, ERK-dependent cell proliferation, as well as enhancement of Src
activation and progression towards a fully transformed state. Accordingly, EVL
accumulates predominantly in premalignant breast lesions and is required for Src
induced epithelial overgrowth in Drosophila. While cell softening allows for
cancer cell invasion, our work reveals that stress fibre-mediated cell stiffening
could drive tumour growth during premalignant stages. A careful consideration of
the mechanical properties of tumour cells could therefore offer new avenues of
exploration when designing cancer-targeting therapies.
PMID- 28508876
TI - Post-supereruption recovery at Toba Caldera.
AB - Large calderas, or supervolcanoes, are sites of the most catastrophic and
hazardous events on Earth, yet the temporal details of post-supereruption
activity, or resurgence, remain largely unknown, limiting our ability to
understand how supervolcanoes work and address their hazards. Toba Caldera,
Indonesia, caused the greatest volcanic catastrophe of the last 100 kyr,
climactically erupting ~74 ka. Since the supereruption, Toba has been in a state
of resurgence but its magmatic and uplift history has remained unclear. Here we
reveal that new 14C, zircon U-Th crystallization and (U-Th)/He ages show
resurgence commenced at 69.7+/-4.5 ka and continued until at least ~2.7 ka,
progressing westward across the caldera, as reflected by post-caldera effusive
lava eruptions and uplifted lake sediment. The major stratovolcano north of Toba,
Sinabung, shows strong geochemical kinship with Toba, and zircons from recent
eruption products suggest Toba's climactic magma reservoir extends beneath
Sinabung and is being tapped during eruptions.
PMID- 28508875
TI - Early phase clinical trials of anticancer agents in children and adolescents - an
ITCC perspective.
AB - In the past decade, the landscape of drug development in oncology has evolved
dramatically; however, this paradigm shift remains to be adopted in early phase
clinical trial designs for studies of molecularly targeted agents and
immunotherapeutic agents in paediatric malignancies. In drug development,
prioritization of drugs on the basis of knowledge of tumour biology, molecular
'drivers' of disease and a drug's mechanism of action, and therapeutic unmet
needs are key elements; these aspects are relevant to early phase paediatric
trials, in which molecular profiling is strongly encouraged. Herein, we describe
the strategy of the Innovative Therapies for Children with Cancer (ITCC)
Consortium, which advocates for the adoption of trial designs that enable
uninterrupted patient recruitment, the extrapolation from studies in adults when
possible, and the inclusion of expansion cohorts. If a drug has neither serious
dose-related toxicities nor a narrow therapeutic index, then studies should
generally be started at the adult recommended phase II dose corrected for body
surface area, and act as dose-confirmation studies. The use of adaptive trial
designs will enable drugs with promising activity to progress rapidly to
randomized studies and, therefore, will substantially accelerate drug development
for children and adolescents with cancer.
PMID- 28508873
TI - Mutant KRAS promotes malignant pleural effusion formation.
AB - Malignant pleural effusion (MPE) is the lethal consequence of various human
cancers metastatic to the pleural cavity. However, the mechanisms responsible for
the development of MPE are still obscure. Here we show that mutant KRAS is
important for MPE induction in mice. Pleural disseminated, mutant KRAS bearing
tumour cells upregulate and systemically release chemokine ligand 2 (CCL2) into
the bloodstream to mobilize myeloid cells from the host bone marrow to the
pleural space via the spleen. These cells promote MPE formation, as indicated by
splenectomy and splenocyte restoration experiments. In addition, KRAS mutations
are frequently detected in human MPE and cell lines isolated thereof, but are
often lost during automated analyses, as indicated by manual versus automated
examination of Sanger sequencing traces. Finally, the novel KRAS inhibitor
deltarasin and a monoclonal antibody directed against CCL2 are equally effective
against an experimental mouse model of MPE, a result that holds promise for
future efficient therapies against the human condition.
PMID- 28508878
TI - Incontinence: The dilemma with comparing efficacy of OAB treatments.
PMID- 28508880
TI - Prostate cancer: 'The prostate' in patients with metastatic prostate cancer: to
treat or not to treat?
PMID- 28508881
TI - Prostate cancer: Circulating free DNA as biomarker.
PMID- 28508877
TI - An overview of female-to-male gender-confirming surgery.
AB - Gender dysphoria is estimated to occur in approximately 25 million people
worldwide, and can have severe psychosocial sequelae. Medical and surgical gender
transition can substantially improve quality-of-life outcomes for individuals
with gender dysphoria. Individuals seeking to undergo female-to-male (FtM)
transition have various surgical options available for gender confirmation,
including facial and chest masculinization, body contouring, and genital surgery.
The World Professional Association for Transgender Health guidelines should be
met before the patient undergoes surgery, to ensure that gender-confirming
surgery is appropriate and indicated. Chest masculinization and metoidioplasty or
phalloplasty are the most common procedures pursued, and both generally result in
high levels of patient satisfaction. Phalloplasty, with a resultant aesthetic and
sensate phallus along with implantable prosthetic, can take upwards of a year to
accomplish, and is associated with a considerable risk of complications. Urethral
complications are most frequent, and can be addressed with revision procedures. A
number of scaffolds, implants, and prostheses are now in development to improve
outcomes in FtM patients.
PMID- 28508883
TI - Corrigendum: Investigating starch gelatinization through Stokes vector resolved
second harmonic generation microscopy.
PMID- 28508882
TI - Voltage-controlled interlayer coupling in perpendicularly magnetized magnetic
tunnel junctions.
AB - Magnetic interlayer coupling is one of the central phenomena in spintronics. It
has been predicted that the sign of interlayer coupling can be manipulated by
electric fields, instead of electric currents, thereby offering a promising low
energy magnetization switching mechanism. Here we present the experimental
demonstration of voltage-controlled interlayer coupling in a new perpendicular
magnetic tunnel junction system with a GdOx tunnel barrier, where a large
perpendicular magnetic anisotropy and a sizable tunnelling magnetoresistance have
been achieved at room temperature. Owing to the interfacial nature of the
magnetism, the ability to move oxygen vacancies within the barrier, and a large
proximity-induced magnetization of GdOx, both the magnitude and the sign of the
interlayer coupling in these junctions can be directly controlled by voltage.
These results pave a new path towards achieving energy-efficient magnetization
switching by controlling interlayer coupling.
PMID- 28508884
TI - A hybrid cloud read aligner based on MinHash and kmer voting that preserves
privacy.
AB - Low-cost clouds can alleviate the compute and storage burden of the genome
sequencing data explosion. However, moving personal genome data analysis to the
cloud can raise serious privacy concerns. Here, we devise a method named Balaur,
a privacy preserving read mapper for hybrid clouds based on locality sensitive
hashing and kmer voting. Balaur can securely outsource a substantial fraction of
the computation to the public cloud, while being highly competitive in accuracy
and speed with non-private state-of-the-art read aligners on short read data. We
also show that the method is significantly faster than the state of the art in
long read mapping. Therefore, Balaur can enable institutions handling massive
genomic data sets to shift part of their analysis to the cloud without
sacrificing accuracy or exposing sensitive information to an untrusted third
party.
PMID- 28508879
TI - Oxidative stress and male infertility.
AB - DNA damage, largely owing to oxidative stress, is a leading cause of defective
sperm function. High levels of oxidative stress result in damage to sperm DNA,
RNA transcripts, and telomeres and, therefore might provide a common underlying
aetiology of male infertility and recurrent pregnancy loss, in addition to
congenital malformations, complex neuropsychiatric disorders, and childhood
cancers in children fathered by men with defective sperm cells. Spermatozoa are
highly vulnerable to oxidative stress owing to limited levels of antioxidant
defence and a single, limited DNA-damage detection and repair mechanism.
Oxidative stress is predominantly caused by a host of lifestyle-related factors,
the majority of which are modifiable. Antioxidant regimens and lifestyle
modifications could both be plausible therapeutic approaches that enable the
burden of oxidative-stress-induced male factor infertility to be overcome.
Lifestyle interventions including yoga and meditation can substantially improve
the integrity of sperm DNA by reducing levels of oxidative DNA damage, regulating
oxidative stress and by increasing the expression of genes responsible for DNA
repair, cell-cycle control and anti-inflammatory effects. Oxidative stress is
caused by various modifiable factors, and the use of simple interventions can
decrease levels of oxidative stress, and therefore reduce the incidence of both
infertility and complex diseases in the resultant offspring.
PMID- 28508885
TI - First Characterisation of Volatile Organic Compounds Emitted by Banana Plants.
AB - Banana (Musa sp.) ranks fourth in term of worldwide fruit production, and has
economical and nutritional key values. The Cavendish cultivars correspond to more
than 90% of the production of dessert banana while cooking cultivars are widely
consumed locally around the banana belt production area. Many plants, if not all,
produce Volatile Organic Compounds (VOCs) as a means of communication with their
environment. Although flower and fruit VOCs have been studied for banana, the
VOCs produced by the plant have never been identified despite their importance in
plant health and development. A volatile collection methodology was optimized to
improve the sensitivity and reproducibility of VOCs analysis from banana plants.
We have identified 11 VOCs for the Cavendish, mainly (E,E)-alpha-farnesene (87.90
+/- 11.28 ng/MUl), methyl salicylate (33.82 +/- 14.29) and 6-methyl-5-hepten-2
one (29.60 +/- 11.66), and 14 VOCs for the Pacific Plantain cultivar, mainly
(Z,E)-alpha-farnesene (799.64 +/- 503.15), (E,E)-alpha-farnesene (571.24 +/-
381.70) and (E) beta ocimene (241.76 +/- 158.49). This exploratory study paves
the way for an in-depth characterisation of VOCs emitted by Musa plants.
PMID- 28508886
TI - Protein-protein interactions and metabolite channelling in the plant
tricarboxylic acid cycle.
AB - Protein complexes of sequential metabolic enzymes, often termed metabolons, may
permit direct channelling of metabolites between the enzymes, providing increased
control over metabolic pathway fluxes. Experimental evidence supporting their
existence in vivo remains fragmentary. In the present study, we test binary
interactions of the proteins constituting the plant tricarboxylic acid (TCA)
cycle. We integrate (semi-)quantitative results from affinity purification-mass
spectrometry, split-luciferase and yeast-two-hybrid assays to generate a single
reliability score for assessing protein-protein interactions. By this approach,
we identify 158 interactions including those between catalytic subunits of
sequential enzymes and between subunits of enzymes mediating non-adjacent
reactions. We reveal channelling of citrate and fumarate in isolated potato
mitochondria by isotope dilution experiments. These results provide evidence for
a functional TCA cycle metabolon in plants, which we discuss in the context of
contemporary understanding of this pathway in other kingdoms.
PMID- 28508888
TI - Association among practice frequency on depression and stress among competitive
US male wheelchair rugby athletes with tetraplegia.
AB - STUDY DESIGN: Cross-sectional. OBJECTIVES: To determine whether frequency of
training is related to self-reported lower psychological distress, defined as
depressive symptomology and perceived stress, among the US male wheelchair rugby
athletes with tetraplegia. SETTING: United States. METHODS: Survey data were
collected on a convenience sample at wheelchair rugby tournaments from January
April 2016. Participants self-reported depressive symptomology (CES-D-10),
perceived stress scale (PSS), and frequency of rugby practice. Covariate-adjusted
regression models were conducted among the full sample and a subsample of
individuals who reported spinal cord injury (SCI) as the nature of their
disability. RESULTS: Participants included 150 males with tetraplegia, and 87%
identified the nature of their disability as SCI. Participants were primarily
Caucasian with an average age of ~35 years. Participants scored low on measures
of depressive symptomology (mean=5.63; s.d.=4.35) and perceived stress
(mean=4.63; s.d.=2.73). Sixty-seven percent of the participants practiced two or
more times per week. Results of the main analyses indicated that practicing
wheelchair rugby two times or more (compared to once a week or less) was
significantly associated with lower depressive symptomology and perceived stress
among the full sample and subsample of individuals with SCI. CONCLUSIONS: Greater
frequency of wheelchair rugby participation was associated with lower levels of
psychological distress. Future research should examine the directional and
mechanistic relationship between frequency of sports participation and
psychological distress to inform the benefits of adaptive sport.
PMID- 28508887
TI - An evolutionary switch in ND2 enables Src kinase regulation of NMDA receptors.
AB - The non-receptor tyrosine kinase Src is a key signalling hub for upregulating the
function of N-methyl D-aspartate receptors (NMDARs). Src is anchored within the
NMDAR complex via NADH dehydrogenase subunit 2 (ND2), a mitochondrially encoded
adaptor protein. The interacting regions between Src and ND2 have been broadly
identified, but the interaction between ND2 and the NMDAR has remained elusive.
Here we generate a homology model of ND2 and dock it onto the NMDAR via the
transmembrane domain of GluN1. This interaction is enabled by the evolutionary
loss of three helices in bilaterian ND2 proteins compared to their ancestral
homologues. We experimentally validate our model and demonstrate that blocking
this interaction with an ND2 fragment identified in our experimental studies
prevents Src-mediated upregulation of NMDAR currents in neurons. Our findings
establish the mode of interaction between an NMDAR accessory protein with one of
the core subunits of the receptor.
PMID- 28508889
TI - Influence of bladder lithiasis on lower urinary tract dynamics in patients with
spinal cord injury.
AB - STUDY DESIGN: A prospective and a case-matched control study. OBJECTIVES: To
study the lower urinary tract dysfunction associated with bladder lithiasis in
patients with spinal cord injury (SCI). SETTING: Toledo (Spain). METHODS: We have
carried out a urodynamic study in 30 patients with SCI with lithiasis in their
bladder before and 3 months after bladder endoscopic lithotripsy. This second
study was compared with the urodynamic findings of a different group of 30
patients with SCI, without a history of bladder lithiasis, paired with cases by
gender and date of urodynamic study. RESULTS: We have found that the prevalence
of neurogenic detrusor overactivity (NDO) was significantly different after
bladder lithotripsy, although the cystomanometric capacity was significantly
increased. A group of patients with lithiasis showed a maximum flow rate, a
voiding maximum detrusor pressure and the detrusor contractility parameter Wmax
lower than that in controls. On the other hand, a voiding abdominal straining was
found to be significantly greater than that in controls. CONCLUSIONS: Bladder
lithiasis affects the presence of NDO in patients with SCI. Patients with SCI who
develop bladder lithiasis present a lower detrusor contractility power compared
with those who do not.
PMID- 28508890
TI - Attentional requirements of postural control in people with spinal cord injury:
the effect of dual task.
AB - STUDY DESIGN: Cross-sectional study. OBJECTIVES: To investigate the attentional
requirements for maintaining standing balance in people with spinal cord injury
(SCI) using a dual-task paradigm and to compare standing balance performance
between SCI and able-bodied (AB) controls. SETTING: LaboratoryMethods:Nine adults
with incomplete SCI, who were able to stand unassisted were recruited, along with
eight AB controls. Subjects performed a dual task involving counting backwards by
3 s out loud while standing with eyes open or closed. The primary outcome
measures were the differences between SCI and control groups for movement
reinvestment and the change in performance between single task and dual task for:
(i) maximum standing time (STime); (ii) error ratio and total number of words
uttered; and (iii) center of pressure measures. Perceptual measures included
perceived mental workload, fear and confidence. RESULTS: SCI subjects stood for
shorter duration during dual task (stand and count) than single task (stand)
compared with controls during eyes closed. Significant differences between groups
were observed for movement reinvestment, center of pressure, perceived mental
effort, fear and confidence. No significant effects were observed for math-task
performance. CONCLUSIONS: Total STime during eyes closed is adversely affected by
the addition of a math task for SCI subjects. Perceptual measures appear to
correspond to increases in postural sway and conscious control of standing in
subjects with SCI. Individuals who can stand for >60 s with eyes closed do not
appear to be significantly affected by the addition of a concurrent secondary
task of minimal mental workload.
PMID- 28508891
TI - Joint morphogenetic cells in the adult mammalian synovium.
AB - The stem cells that safeguard synovial joints in adulthood are undefined. Studies
on mesenchymal stromal/stem cells (MSCs) have mainly focused on bone marrow. Here
we show that lineage tracing of Gdf5-expressing joint interzone cells identifies
in adult mouse synovium an MSC population largely negative for the skeletal stem
cell markers Nestin-GFP, Leptin receptor and Gremlin1. Following cartilage
injury, Gdf5-lineage cells underpin synovial hyperplasia through proliferation,
are recruited to a Nestin-GFPhigh perivascular population, and contribute to
cartilage repair. The transcriptional co-factor Yap is upregulated after injury,
and its conditional ablation in Gdf5-lineage cells prevents synovial lining
hyperplasia and decreases contribution of Gdf5-lineage cells to cartilage repair.
Cultured Gdf5-lineage cells exhibit progenitor activity for stable chondrocytes
and are able to self-organize three-dimensionally to form a synovial lining-like
layer. Finally, human synovial MSCs transduced with Bmp7 display morphogenetic
properties by patterning a joint-like organ in vivo. Our findings further the
understanding of the skeletal stem/progenitor cells in adult life.
PMID- 28508892
TI - High precision hyperfine measurements in Bismuth challenge bound-state strong
field QED.
AB - Electrons bound in highly charged heavy ions such as hydrogen-like bismuth
209Bi82+ experience electromagnetic fields that are a million times stronger than
in light atoms. Measuring the wavelength of light emitted and absorbed by these
ions is therefore a sensitive testing ground for quantum electrodynamical (QED)
effects and especially the electron-nucleus interaction under such extreme
conditions. However, insufficient knowledge of the nuclear structure has
prevented a rigorous test of strong-field QED. Here we present a measurement of
the so-called specific difference between the hyperfine splittings in hydrogen
like and lithium-like bismuth 209Bi82+,80+ with a precision that is improved by
more than an order of magnitude. Even though this quantity is believed to be
largely insensitive to nuclear structure and therefore the most decisive test of
QED in the strong magnetic field regime, we find a 7-sigma discrepancy compared
with the theoretical prediction.
PMID- 28508893
TI - South-American plate advance and forced Andean trench retreat as drivers for
transient flat subduction episodes.
AB - At two trench segments below the Andes, the Nazca Plate is subducting sub
horizontally over ~200-300 km, thought to result from a combination of buoyant
oceanic-plateau subduction and hydrodynamic mantle-wedge suction. Whether the
actual conditions for both processes to work in concert existed is uncertain.
Here we infer from a tectonic reconstruction of the Andes constructed in a mantle
reference frame that the Nazca slab has retreated at ~2 cm per year since ~50 Ma.
In the flat slab portions, no rollback has occurred since their formation at ~12
Ma, generating 'horse-shoe' slab geometries. We propose that, in concert with
other drivers, an overpressured sub-slab mantle supporting the weight of the slab
in an advancing upper plate-motion setting can locally impede rollback and
maintain flat slabs until slab tearing releases the overpressure. Tear subduction
re-establishes a continuous slab and allows the process to recur, providing a
mechanism for the transient character of flat slabs.
PMID- 28508894
TI - Factoring in CD4 T cells during treatment of HIV.
PMID- 28508895
TI - Exosomes maintain cellular homeostasis by excreting harmful DNA from cells.
AB - Emerging evidence is revealing that exosomes contribute to many aspects of
physiology and disease through intercellular communication. However, the
biological roles of exosome secretion in exosome-secreting cells have remained
largely unexplored. Here we show that exosome secretion plays a crucial role in
maintaining cellular homeostasis in exosome-secreting cells. The inhibition of
exosome secretion results in the accumulation of nuclear DNA in the cytoplasm,
thereby causing the activation of cytoplasmic DNA sensing machinery. This event
provokes the innate immune response, leading to reactive oxygen species (ROS)
dependent DNA damage response and thus induce senescence-like cell-cycle arrest
or apoptosis in normal human cells. These results, in conjunction with
observations that exosomes contain various lengths of chromosomal DNA fragments,
indicate that exosome secretion maintains cellular homeostasis by removing
harmful cytoplasmic DNA from cells. Together, these findings enhance our
understanding of exosome biology, and provide valuable new insights into the
control of cellular homeostasis.
PMID- 28508896
TI - Obesity-related CpG Methylation (cg07814318) of Kruppel-like Factor-13 (KLF13)
Gene with Childhood Obesity and its cis-Methylation Quantitative Loci.
AB - The cg07814318 hypermethylation of Kruppel-like factor 13 (KLF13) gene has been
reported for its relevancy with Body Mass Index (BMI) from European origin. We
explored the cg07814318 methylation and its cis-meQTL (cis-methylation
quantitative loci) of KLF13 from a childhood obesity cohort. The cg07814318
methylation in blood was significantly associated with obesity and correlated
with several obesity-related physical and biochemical traits. We examined the
same loci from purified three human cell types (n = 47), i.e., pre-adipocytes,
adipocytes and islets. The cg07814318 methylation pattern in pre-adipocytes and
islets were significant higher in cells from subjects with a higher BMI compared
with control subjects. By exome sequencing of KLF13 gene in blood with the same
cohort, we found nine SNPs (single nucleotide polymorphisms) within its gene
body, and two SNPs (rs11537749 and rs12595641) were as cis-meQTL of cg07814318.
There was the 2.01% methylation change of cg07814318 between homozygous dominant
and recessive genotypes, especially, in rs12595641. The sequencing variations
within KLF13 genes could drive dynamic modifications of obesity-related CpG
methylation. Differential DNA methylation patterns in the KLF13 gene determined
from separate blood samples showed that this criterion could be used as a
surrogate for representing overall epigenetic changes in cells related to
obesity.
PMID- 28508898
TI - Dicyanoaurate-based heterobimetallic uranyl coordination polymers.
AB - The first series of uranyl ([UO2]2+)-dicyanoaurate coordination polymers and
molecular complexes has been synthesized. Reactions of [A][Au(CN)2] (A = [nBu4N]+
or [(Ph3P)2N]+ ([PPN])) and uranyl nitrate in alcoholic solvents in ambient light
led to [A]2[(UO2)2(MU-eta2:eta2-O2)(NO3)2(MU-Au(CN)2)2], which incorporates
peroxo ligands into a one-dimensional ladder topology with alternating aurophilic
and peroxo rungs. Conducting the reaction with non-alcoholic solvents formed two
polymorphs of a one-dimensional chain, [PPN][UO2(NO3)2Au(CN)2], from acetone, and
a molecular analogue, [PPN]2[UO2(NO3)2(Au(CN)2)2], from acetonitrile, none of
which exhibited aurophilic interactions. The addition of 2,2'-bipyridine to the
initial reaction resulted in [UO2(bipy)(MeO)(MeOH)]2[(MU-Au(CN)2)(Au(CN)2)], a
one-dimensional structure which propagates via a series of linear aurophilic
bonds with pendant uranyl complexes; methanol and methoxy ligands provide
additional connections through hydrogen bonding. The addition of 5,5'-dimethyl
2,2'-bipyridine using solvothermal conditions resulted in the one-dimensional
ladder [UO2(Me2bipy)Au(CN)2]2[(MU-OH)2], generated through aurophilic bonds and
hydroxide ligands. The incorporation of 2,2':6',2''-terpyridine (terpy) using
solvothermal conditions resulted in [[UO2(terpy)]2(MU-NO3)(MU-O)][Au(CN)2], a
molecular salt with no aurophilic interactions. Emission spectra attributable to
aurophilic interactions are observed in [nBu4N]2[(UO2)2(MU-eta2:eta2-O2)(NO3)2(MU
Au(CN)2)2], while all others only show emission typical of the uranyl cation.
PMID- 28508899
TI - The quasi-unchanged gas-phase molecular structures of the atmospheric aerosol
precursor beta-pinene and its oxidation product nopinone.
AB - The rotational spectra of the two bicyclic molecules beta-pinene and its
oxidation product nopinone were investigated in the gas phase, using Fourier
transform microwave spectroscopy coupled to a supersonic jet, in the 2-20 GHz
range. The parent species and all heavy atom isotopologues have been observed in
their natural abundance. The spectroscopic parameters of the ground states were
determined from a Watson's Hamiltonian in the A reduction. The rotational
constants were used together with geometrical parameters obtained from ab initio
calculations to determine the r0 and r structures of the skeletons, without any
structural assumption in the fit concerning the heavy atoms. Comparison with
solid phase and other bicyclic monoterpenes unveiled an unprecedented complete
set of geometrical parameters for the rigid cages. The structures of beta-pinene
and nopinone are very close, except for the substituents at C2. In the gas phase
C2 is a centre of planarity in both molecules.
PMID- 28508901
TI - From polyethylene waxes to HDPE using an alpha,alpha'-bis(arylimino)-2,3:5,6
bis(pentamethylene)pyridyl-chromium(iii) chloride pre-catalyst in ethylene
polymerisation.
AB - Five examples of alpha,alpha'-bis(arylimino)-2,3:5,6-bis(pentamethylene)pyridyl
chromium(iii) chlorides (aryl = 2,6-Me2Ph Cr1, 2,6-Et2Ph Cr2, 2,6-i-Pr2Ph Cr3,
2,4,6-Me3Ph Cr4, 2,6-Et2-4-MePh Cr5) have been synthesized by the one-pot
template reaction of alpha,alpha'-dioxo-2,3:5,6-bis(pentamethylene)pyridine,
CrCl3.6H2O and the corresponding aniline. The molecular structures of Cr1 and Cr4
reveal distorted octahedral geometries with the N,N,N-ligand adopting a mer
configuration. On activation with an aluminium alkyl co-catalyst, Cr1-Cr5
exhibited high catalytic activities in ethylene polymerization and showed
outstanding thermal stability operating effectively at 80 degrees C with
activities up to 1.49 * 107 g of PE (mol of Cr)-1 h-1. Significantly, the nature
of the co-catalyst employed had a dramatic effect on the molecular weight of the
polymeric material obtained. For example, using diethylaluminium chloride
(Et2AlCl) in combination with Cr4 gave high density/high molecular weight
polyethylene with broad molecular weight distributions (30.9-39.3). By contrast,
using modified methylaluminoxane (MMAO), strictly linear polyethylene waxes of
lower molecular weight and narrow molecular weight distribution (1.6-2.0) were
obtained with vinyl end-groups.
PMID- 28508902
TI - Non-zeolitic properties of the dipeptide l-leucyl-l-leucine as a result of the
specific nanostructure formation.
AB - The non-zeolitic behavior of l-leucyl-l-leucine and its self-organization in
solid state and from solutions with the formation of different nanostructures are
reported. This dipeptide forms porous crystals, but does not exhibit molecular
sieve effects typical of classical zeolites and biozeolites. The specific
sorption properties of l-leucyl-l-leucine result from a change in its crystal
packing from channel-type to layered-type, when binding strong proton acceptors
or proton donors of molecular size greater than 18-20 cm3 mol-1. The high
sorption capacity of l-leucyl-l-leucine toward dichloromethane results from the
self-organization of the dipeptide, by forming nanofibers or web-like structures.
The low thermal stability of clathrates of the dipeptide containing large guest
molecules and the selectivity of l-leucyl-l-leucine toward alcohols over nitriles
can be used to separate organic mixtures such as methanol/n-butanol and
methanol/acetonitrile.
PMID- 28508903
TI - Protonation-modulated localization of excess electrons in histidine aqueous
solutions revealed by ab initio molecular dynamics simulations: anion-centered
versus cation-centered localization.
AB - In this work, we present an ab initio molecular dynamics simulation study on the
interaction of an excess electron (EE) with histidine in its aqueous solution.
Two different configurations of histidine (imidazole group protonated or not) are
considered to reflect its different existing forms in neutral or slightly acidic
surroundings. The simulation results indicate that localizations of EEs in
different aqueous histidine solutions are quite different and are strongly
affected by protonation of the side chain imidazole group and are thus pH
controlled. In neutral aqueous histidine solution, an EE localizes onto the
carboxyl anionic group of the amino acid backbone after a relatively lengthy
diffuse state, performing just like in an aliphatic amino acid solution. But in
weakly acidic solution in which the side chain imidazole group is protonated, an
EE undergoes a short lifetime diffuse state and finally localizes on the
protonated imidazole group. We carefully examine these two different localization
dynamics processes and analyze the competition between different dominating
groups in their corresponding electron localization mechanisms. To explain the
difference, we investigate the frontier molecular orbitals of these two systems
and find that their energy levels and compositions are important to determine
these differences. These findings can provide helpful information to understand
the interaction mechanisms of low energy EEs with amino acids and even
oligopeptides, especially with aromatic rings.
PMID- 28508905
TI - An eco-friendly in situ activatable antibiotic via cucurbit[8]uril-mediated
supramolecular crosslinking of branched polyethylenimine.
AB - We report an unprecedented, eco-friendly, in situ activatable model antibiotic,
phenylalanyl-polyethylenimine (PhePEI), to potentially diminish antibiotic
pollution of the environment and associated antibiotic resistance. The inactive
PhePEI can be reversibly activated upon supramolecular crosslinking by
cucurbit[8]uril, conferring potent antibacterial activity.
PMID- 28508904
TI - Chloride-accelerated Cu-Fenton chemistry for biofilm removal.
AB - Biofilms present challenges to numerous industries. Herein, a simple approach was
developed based on chloride-accelerated Fenton chemistry, where copper oxide
nanoparticles facilitate efficient generation of reactive chlorine species for
biofilm removal.
PMID- 28508907
TI - An effective trigger for energy release of vinylheptafulvene-based solar heat
batteries.
AB - Stoichiometric copper(i) tetrakis(acetonitrile) is found to activate the thermal
ring-closure reaction of a series of high-energy vinylheptafulvene isomers to the
corresponding low-energy and photoactive dihydroazulenes, allowing the release of
energy upon request.
PMID- 28508897
TI - Whole genome analysis of a schistosomiasis-transmitting freshwater snail.
AB - Biomphalaria snails are instrumental in transmission of the human blood fluke
Schistosoma mansoni. With the World Health Organization's goal to eliminate
schistosomiasis as a global health problem by 2025, there is now renewed emphasis
on snail control. Here, we characterize the genome of Biomphalaria glabrata, a
lophotrochozoan protostome, and provide timely and important information on snail
biology. We describe aspects of phero-perception, stress responses, immune
function and regulation of gene expression that support the persistence of B.
glabrata in the field and may define this species as a suitable snail host for S.
mansoni. We identify several potential targets for developing novel control
measures aimed at reducing snail-mediated transmission of schistosomiasis.
PMID- 28508908
TI - Rapid synthesis of CuInTe2 ultrathin nanoplates with enhanced
photoelectrochemical properties.
AB - Ultrathin (2.1 +/- 0.1 nm) single-crystal CuInTe2 two-dimensional (2D) nanoplates
were synthesized via a rapid colloidal synthesis method. The growth mechanism was
investigated in detail. Crystal seeds grew via a 2D assembly process of initially
formed small CuInTe2 nanoparticles followed by recrystallization into single
crystal nanoplates. The obtained CuInTe2 nanoplates exhibited significantly
enhanced photoelectrochemical properties compared with the CuInTe2 nanoparticles,
benefitting from their ultrathin 2D characteristics.
PMID- 28508909
TI - Pinpointing disulfide connectivities in cysteine-rich proteins.
AB - A simple MD-based protocol is presented to accurately predict both the sequence
and order of disulfide bond formation in proteins containing multiple cysteine
residues. It provides a detailed description of their dynamical and structural
features, which can be used to perform ensemble-averaged ECD calculations. Plant
cyclotides are used as model compounds.
PMID- 28508912
TI - Pyrazine-fused isoindigo: a new building block for polymer solar cells with high
open circuit voltage.
AB - Pyrazine-fused isoindigo (PzIIG) was designed and synthesized as a novel electron
acceptor to construct two D-A conjugated polymers, PzIIG-BDT2TC8 and PzIIG
BTT2TC10. Both the polymers were successfully applied in polymer solar cells, and
the PzIIG-BDT2TC8 based solar cell device exhibited a PCE of 5.26% with a high
Voc over 1.0 V.
PMID- 28508913
TI - Digitally encoded silica microparticles for multiplexed nucleic acid detection.
AB - A robust high throughput suspension array was proposed to analyze biomolecules.
To exploit its capacity for nucleic acid detection, we designed a multiplex
nested asymmetric PCR (MNAS PCR) that can produce single stranded DNA (ssDNA)
efficiently without complicated optimization. Multiplexed HPV genotyping was
demonstrated with high selectivity, high sensitivity and rapid hybridization
within 20 minutes.
PMID- 28508914
TI - Photoexcited Ag ejection from a low-temperature He cluster: a simulation study by
nonadiabatic Ehrenfest ring-polymer molecular dynamics.
AB - Ring-polymer molecular dynamics (RPMD) simulations have been performed to
understand the photoexcitation dynamics of an Ag atom embedded in a low
temperature cluster consisting of 500 helium atoms, after the electronic
excitation 5p 2P1/2 <- 5p 2S1/2 and 5p 2P3/2 <- 5p 2S1/2 of the Ag atom. Along
the RPMD trajectory the time evolution of electronic wavefunction within the spin
orbit 2P manifold is calculated, whereby the time-dependent Schrodinger equation
and the RPMD equation of motion are coupled, using the a la Ehrenfest mean field
approach. It is found from the simulations that the Ag atom is ejected from the
helium cluster with the average time of 100 ps after photoexcitation with the
average ejection velocity being 60-70 m s-1, which is roughly in line with
experiment. Meanwhile it is also found that the present simulations do not agree
with experiment as to the final state of the ejected Ag atom.
PMID- 28508915
TI - Avoiding the invasion of H2O into Y2Mo3O12 by coating with C3N4 to improve
negative thermal expansion properties.
AB - The hygroscopicity of Y2Mo3O12 has serious influences on its mechanic and
negative thermal expansion (NTE) properties. The reported partial ion
substitution for Y3+ in Y2Mo3O12 could reduce the hygroscopicity, however, the
expected NTE properties disappear disappointedly. In this investigation, it is
found that avoiding the invasion of crystal water and extending the NTE
temperature range of Y2Mo3O12 to room temperature could be realized together by
heating with CO(NH2)2. The X-ray diffraction patterns, infrared absorption
spectra, scanning electron microscopy images and X-ray photoelectron spectra
suggest the formation of small hydrophobic molecules (C3N4, C, etc.) coated on
the surface, which could clog the microchannels in Y2Mo3O12 to avoid the invasion
of crystal water. The investigation paves a way to improve the NTE properties by
neglecting the influences of water molecules on the stretching vibrations of MoO4
tetrahedra and the transverse vibrations of bridge oxygen atoms.
PMID- 28508916
TI - Direct oral anticoagulants for the treatment of cancer-associated venous
thromboembolism. What do we know so far?
AB - Cancer patients with venous thromboembolism (VTE) are at increased risk for both
bleeding and VTE recurrence. Anticoagulation with low-molecular-weight heparin
(LMWH) is the standard of care during the initial and long-term treatment phase
(i.e. during the first 3 - 6 months of therapy) based on its overall beneficial
safety and efficacy profile compared to vitamin K antagonists (VKAs). The direct
oral anticoagulants (DOACs) rivaroxaban, apixaban, edoxaban, and dabigatran are
approved for the treatment of acute VTE, and the combined six phase-3 trials have
included > 1500 patients with active cancer, as defined by variable selection
criteria. Subgroup analyses of these patients, either pooled or separately
reported, suggest that DOACs could be a safe and efficacious alternative to VKA
therapy for the treatment of cancer-associated VTE. However, the populations of
cancer patients included in the DOAC and LMWH trials are not comparable with
regard to mortality and VTE risk, and no specific data from direct head-to-head
comparisons of DOACs with LMWHs are currently available. The use of DOACs for the
management of VTE in cancer is thus not recommended by clinical practice
guidelines.
PMID- 28508917
TI - [Dowel pinning for metacarpal and metatarsal fractures in dogs].
AB - OBJECTIVE: To evaluate a dowel pinning technique for metacarpal and metatarsal
fractures in dogs. MATERIAL AND METHODS: Medical records of 13 dogs with complete
clinical and radiographic follow-up examinations after a median observation time
of 5 months were evaluated retrospectively. Assessment included fracture data,
number of stabilized bones versus number of fractured bones and parameters of
internal fixation including postoperative axial alignment and position of
implants assessed on serial radiographs. Complications during the healing period
and the final radiographic and functional outcome were analysed in relation to
the details of fracture fixation. RESULTS: Most dogs in this study (mean age: 2.9
years, mean weight: 9.9 kg) had fractures of three or four bones, and fractures
were closed in all but one dog. All fractures involved the metacarpal/metatarsal
body, and all but five were transverse. The size of Kirschner wires used for
dowel pinning ranged from 0.8 to 2.0 mm, and the length in relation to bone
length ranged from 39 to 91%. Axial alignment of internal fixation was and
remained anatomically correct and the dowel pins remained in place in all but one
dog. This dog had open metatarsal fractures and dowel pinning was
contraindicated. Additionally, the Kirschner wires perforated the cortex of the
proximal segments, which resulted in implant migration, malunion and residual
lameness. The other dogs achieved complete functional union even though seven of
13 dogs developed radiographic signs of synostosis. CLINICAL SIGNIFICANCE:
Although the number of dogs in this study was small, dowel pinning was shown to
be technically straightforward, inexpensive and effective for surgical repair of
canine metacarpal and metatarsal bone fractures. Further studies should focus on
the need for and duration of additional external coaptation.
PMID- 28508918
TI - [Local anaesthesia in ruminants].
AB - The use of local anaesthesia in ruminants allows many surgical procedures to be
conducted free of pain, efficiently and inexpensively in the field. Local
anaesthesia combined with sedation and immobilisation of the animal can replace
general anaesthesia for many procedures (e. g. castration, claw amputation). The
level of difficulty differs among various local anaesthetic techniques: local
infiltration of tissue or anaesthesia of the cornual nerve are easily performed,
whereas local anaesthesia of the eye, regional anaesthesia in limbs or
anaesthesia for umbilical surgery are more difficult to carry out. This article
presents an illustrated overview of the most common local anaesthetic procedures
in cattle as well as in small ruminants and serves as a practical guide for
veterinarians in the field. In principle, these techniques can likewise be
applied in other ruminants or artiodactyls.
PMID- 28508919
TI - Cognitive Development of School-Age Hypoplastic Left Heart Syndrome Survivors: A
Single Center Study.
AB - Neurological and radiologic research results show an abnormal cerebral
microstructure as well as abnormal neurodevelopment in patients treated for
hypoplastic left heart syndrome. The aim of this study was to assess the varying
cognitive performance these children have developed in dependence upon prenatal
diagnosis, surgical techniques, surgical learning effects, anatomy, perfusion
techniques, gender, pedagogic, and sociodemographic parameters in comparison to
age-adjusted normative values. School-age children (6.3-16.9 years) with
hypoplastic left heart syndrome, who were treated at the Children's heart Center
Linz between 1997 and 2009, (n = 74), were surveyed in reference to cognitive
achievements. 43 patients were examined prospectively by psychologists using the
Wechsler intelligence scale for children IV in order to determine the respective
total intelligence quotient index for each child's developmental stage. The mean
index was 84.5 (percentile rank 26.4). The statistical spread and standard
deviation ranged from a minimum of 40 to a maximum of 134 +/- 20.8. The results
for verbal comprehension, perceptual reasoning, and processing speed corresponded
with total index results and were thus lower than the mean value of the normative
values. The assessment of working memory showed results in the average. Prenatal
diagnosis, type of lung perfusion, anatomy, and various cerebral perfusion
techniques did not significantly affect the cognitive results of the patients.
The results show that hypoplastic left heart syndrome patients can be
successfully tutored formally as well as personally in cognitive areas, although
when compared to healthy children, they showed lower results for intellectual
area parameters.
PMID- 28508920
TI - Chronic Low Dose Prostaglandin and Neonatal Heart Block.
AB - Long-term prostaglandin use is commonly associated with side effects such as
cortical proliferation of the bones, hypertrophic pyloric stenosis, and soft
tissue swelling of the extremities. We report a neonate with critical coarctation
of the aorta, who developed second and third degree atrioventricular blocks
associated with prolonged prostaglandin E1 (PGE1) infusion. Interestingly, these
conduction blocks only occurred at low PGE1 dose. The rhythm disturbances
resolved promptly with the discontinuation of PGE1 following surgical repair.
PMID- 28508922
TI - Adaptation and optimization of a fluorescence-based assay for in vivo
antimalarial drug screening.
AB - The in vivo efficacy of potential antimalarials is usually evaluated by direct
microscopic determination of the parasitaemia of Plasmodium-infected mice on
Giemsa-stained blood smears. This process is time-consuming, requires experienced
technicians and is not automatable. Therefore, we optimized a SYBR Green I (SYBRG
I) fluorescence-based assay to fluorometers commonly available in many research
laboratories. This technique was originally developed to assess parasitaemia in
humans by cytometry. We defined optimal conditions with Plasmodium berghei
infected mice, standard lysis buffer (Tris, EDTA, saponin and Triton), whole
blood cells and 2 h staining incubation with SYBRG I 2X. The fluorescence
background generated by uninfected whole blood cells was low (around 4.6%), and
the linearity high (r 2 = 0.96), with parasitaemia ranging from 1.4 to 60%. The
Bland-Altman plot showed a strong correlation between SYBRG I and Giemsa gold
standard method; Z'-factor was >0.5. These findings suggest that our fluorescence
based assay is suitable for in vivo antimalarial drug assessment in a malaria
murine model. It can help to overcome the human bias found with microscopic
techniques.
PMID- 28508921
TI - Latent factor structure of a behavioral economic marijuana demand curve.
AB - RATIONALE: Drug demand, or relative value, can be assessed via analysis of
behavioral economic purchase task performance. Five demand indices are typically
obtained from drug purchase tasks. OBJECTIVES: The goal of this research was to
determine whether metrics of marijuana reinforcement from a marijuana purchase
task (MPT) exhibit a latent factor structure that efficiently characterizes
marijuana demand. METHODS: Participants were regular marijuana users (n = 99;
37.4% female, 71.5% marijuana use days [5 days/week], 15.2% cannabis dependent)
who completed study assessments, including the MPT, during a baseline session.
Principal component analysis was used to examine the latent structure underlying
MPT indices. Concurrent validity was assessed via examination of relationships
between latent factors and marijuana use, past quit attempts, and marijuana
expectancies. RESULTS: A two-factor solution was confirmed as the best fitting
structure, accounting for 88.5% of the overall variance. Factor 1 (65.8%
variance) reflected "Persistence," indicating sensitivity to escalating marijuana
price, which comprised four MPT indices (elasticity, O max, P max, and
breakpoint). Factor 2 (22.7% variance) reflected "Amplitude," indicating the
amount consumed at unrestricted price (intensity). Persistence factor scores were
associated with fewer past marijuana quit attempts and lower expectancies of
negative use outcomes. Amplitude factor scores were associated with more frequent
use, dependence symptoms, craving severity, and positive marijuana outcome
expectancies. CONCLUSIONS: Consistent with research on alcohol and cigarette
purchase tasks, the MPT can be characterized with a latent two-factor structure.
Thus, demand for marijuana appears to encompass distinct dimensions of price
sensitivity and volumetric consumption, with differential relations to other
aspects of marijuana motivation.
PMID- 28508923
TI - Biomarkers of oxidative damage in bacteria for the assessment of sanitation
efficacy in lettuce wash water.
AB - In the fresh produce industry, validation of sanitation efficacy is critical to
prevent cross-contamination of produce. The current validation approaches are
either based on time-consuming plate counting assays or indirect measurements of
chemical properties of wash water. In the study, the focus was to identify
biomarkers that can provide direct assessment of oxidative damage in bacteria
upon exposure to sanitizers in the presence of fresh produce and correlation of
these oxidative biomarkers with logarithmic inactivation of bacteria. Two
endogenous bacterial biomarkers, protein carbonylation and thiol oxidation, were
evaluated for assessing oxidative damage in Escherichia coli O157:H7 and Listeria
innocua during sanitation of pre-cut lettuce leaves with NaOCl or H2O2. Results
show that NaOCl treatment was more effective than H2O2 for oxidation of both the
intracellular thiols and protein carbonylation in the selected strains.
Statistical analysis of the measurements illustrates that oxidation of the
intracellular thiol induced by NaOCl or H2O2 was correlated with logarithmic
reduction of E. coli O157:H7 and L. innocua. In contrast, changes in the protein
carbonylation content were not correlated with reduction in bacterial cell
viability. In summary, these results provide a novel approach to validate
sanitation efficacy for the fresh produce industry.
PMID- 28508924
TI - Intractable epistaxis: which arteries are responsible? An angiographic study.
AB - PURPOSE: Epistaxis constitutes a significant proportion of the Otolaryngologist's
emergency workload. Optimal management differs in relation to the anatomic origin
of the bleeding. The outcome of our study was to determine which artery(ies)
could be considered as the cause of severe bleeding in the context of severe
epistaxis. METHODS: Fifty-five procedures of embolization preceded by angiography
were reviewed. Medical records of interventionally treated patients were analysed
for demographics, medical history, risk factors and clinical data. Angiographic
findings were also assessed for active contrast extravasation (blush), vascular
abnormality and embolised artery. RESULTS: Previous angiography showed an active
contrast extravasation in only 20 procedures. The most common bleeding source was
the sphenopalatine artery (SPA) followed by anterior ethmoidal artery (AEA) and
facial artery. Majority of multiple or bilateral extravasations occured in
patients with systemic factors. CONCLUSIONS: A better understanding of the
potential bleeding source might help and limit the risk of treatment failures.
Our study confirms that the SPA is the most common cause of severe bleeding. We
also emphasise the role of the AEA not only in traumatic context. Others arteries
are rarely involved except in patients with comorbidities or frequent
recurrences.
PMID- 28508925
TI - Using MALDI-TOF MS imaging and LC-HRMS for the investigation of the degradation
of polycaprolactone diol exposed to different wastewater treatments.
AB - Polymers are used in high amounts in a wide range of applications from
biomedicine to industry. Because of the growing awareness of the increasing
amounts of plastic wastes in the aquatic environment during recent years, the
evaluation of their biodegradability deserves special attention. In the past,
most efforts were dedicated to studying the biodegradation of polyesters in soil
and compost, while very little research has been conducted on their fate in
wastewater. Here, we assessed the ability of bacterial communities residing in
the aerobic and denitrification tank from a wastewater treatment plant (WWTP) to
degrade the polymeric ester polycaprolactone diol (PCLD; average molecular weight
of 1250 Da). Following the incubation of the solid polymer in WWTP tanks, matrix
assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) was
used to provide evidence for hydrolytic reactions and to study differences in the
spatial degradation on the PCLD surface. It was demonstrated that regardless of
the wastewater type, the chemical structure on the PCLD surface underwent
modifications after 7 days of exposure. Apart from the parent PCLD peak series in
MALDI-MSI mass spectra, the presence of a second oligomer series with mass peaks
spaced by m/z 114 (as in PCLD) was observed. It was proposed to correspond to
polycaprolactone (PCL) originating from the hydrolytic cleavage of the diethylene
glycol from PCLD. Their ion masses were detected at m/z 104 below the PCLD peaks
and their structures were proposed as PCL cyclized oligomers. Differences in the
spatial distribution of low MW ions (<800) between the aerobic and denitrifying
exposed samples in MALDI MSI were also noticeable. While the ions at m/z 221.1,
247.1 and 449.2 predominated in the aerobic exposed sample, those at m/z 475.5
and 677.4 were characteristic of the denitrifying one. The MALDI-MSI measurements
in the low mass range were complemented with LC-HRMS analysis to determine
plausible structures of the major degradation products. Ten transformation
products (TPs) were detected in the denitrifying wastewater experiment, five of
them were the result of ester hydrolysis forming caprolactone oligomers (TPs 220,
334, 448, 562, and 676) while the other series corresponded to formation of PCL
chain with a terminal diethylene glycol, likewise formed by ester hydrolysis (TPs
246, 360, 474, 588, and 702). Graphical abstract Investigation of the polymer
degradation in WWTPs by MALDI-MSI and LC-HRMS.
PMID- 28508926
TI - Abundance and Co-Distribution of Widespread Marine Archaeal Lineages in Surface
Sediments of Freshwater Water Bodies across the Iberian Peninsula.
AB - Archaea inhabiting marine and freshwater sediments have a relevant role in
organic carbon mineralization, affecting carbon fluxes at a global scale. Despite
current evidences suggesting that freshwater sediments largely contribute to this
process, few large-scale surveys have been addressed to uncover archaeal
diversity and abundance in freshwater sedimentary habitats. In this work, we
quantified and high-throughput sequenced the archaeal 16S rRNA gene from
surficial sediments collected in 21 inland waterbodies across the Iberian
Peninsula differing in typology and trophic status. Whereas methanogenic groups
were dominant in most of the studied systems, especially in organic-rich
sediments, archaea affiliated to widespread marine lineages (the Bathyarchaeota
and the Thermoplasmata) were also ubiquitous and particularly abundant in euxinic
sediments. In these systems, Bathyarchaeota communities were dominated by
subgroups Bathyarchaeota-6 (87.95 +/- 12.71%) and Bathyarchaeota-15 (8.17 +/-
9.2%) whereas communities of Thermoplasmata were mainly composed of members of
the order Thermoplasmatales. Our results also indicate that Archaea accounted for
a minor fraction of sedimentary prokaryotes despite remarkable exceptions in
reservoirs and some stratified lakes. Copy numbers of archaeal and
bathyarchaeotal 16S rRNA genes were significantly different when compared
according to system type (i.e., lakes, ponds, and reservoirs), but no differences
were obtained when compared according to their trophic status (from oligotrophy
to eutrophy). Interestingly, we obtained significant correlations between the
abundance of reads (Spearman r = 0.5, p = 0.021) and OTU richness (Spearman r =
0.677, p < 0.001) of Bathyarchaeota and Thermoplasmata across systems,
reinforcing the hypothesis of a potential syntrophic interaction between members
of both lineages.
PMID- 28508927
TI - Tumor LXR Expression is a Prognostic Marker for Patients with Hepatocellular
Carcinoma.
AB - Liver X receptor (LXR) activation exerts an anti-tumor effect. However, whether
the tumor LXR expression has prognostic significance in hepatocellular carcinoma
(HCC) patient has not been addressed yet. Primary HCC and the adjacent non-tumor
tissues were obtained from 169 patients who underwent routine curative surgical
treatment. All patients were followed for prognosis analyses. Tumor LXR was
detected by immunohistochemical analysis. In in vitro study, several HCC cell
lines were cultured for cellular protein detection of LXR and other cytokines,
including nuclear factor kappa (NFkappaB), Matrix metalloproteinases 2 and 9 (MMP
2 and -9). Meanwhile, the invasion ability of cultured HCC cell lines was
performed. We found that LXR expression status in tumor samples is associated
with the clinical characteristics, such as tumor stage and metastasis, of HCC
patients. Prognosis analysis shows that tumor LXR expression status is closely
related to the post-operative outcome in HCC patients who underwent surgical
treatment. Patients with low LXR expression have a significantly lower mean 5
year overall survival rate and mean overall survival period than those with high
LXR level. Our in vitro data reveal that HCC cell lines had increased NF-kappaB,
MMP2, MMP9 and invasive ability than normal cell line, which are suppressed by
LXR activation via NFkappaB pathway. Our data suggest that LXR could be used as a
biomarker for HCC prognosis. Further study is warranted to explore the molecular
mechanism under which LXR regulates tumor behaves.
PMID- 28508928
TI - Embryonal tumors in Canadian children less than 36 months of age: results from
the Canadian Pediatric Brain Tumor Consortium (CPBTC).
AB - Embryonal tumors are a heterogeneous group of central nervous system (CNS) tumors
whose subgroups have varying incidence and outcome. Despite these differences,
they are often grouped as a single entity for study purposes. To date, there are
no Canadian multi-institutional studies examining the incidence and outcome of
all embryonal subtypes. The current study is an observational study reviewing
embryonal tumors in all patients less than 36 months of age diagnosed with a CNS
tumor in Canada from 1990 to 2005. Embryonal tumors accounted for 26.9% of all
CNS tumors. Medulloblastomas were the highest proportion of the embryonal tumors
at 61.5%. Atypical teratoid/rhabdoid tumors (AT/RT) had the second highest
proportion of embryonal tumors at 18%. The proportion of primitive
neuroectodermal tumors (PNET) was 16%, with 2.6 and 1.9% for congenital
medulloepithelioma and ependymoblastoma tumors, respectively. AT/RT and PNET were
more common in younger age groups. Medulloblastoma became more prevalent with
increasing age, with its highest prevalence in the 25 to 36 month age group.
Survival rates for our Canadian population at 18 and 24 months were 0.74 and 0.68
for medulloblastoma, 0.64 and 0.60 for PNET, and 0.36 and 0.29 for AT/RT,
respectively. Overall, our data are comparable with published international rates
for embryonal tumors. These incidence and outcome figures can guide future
research into these rare tumors.
PMID- 28508929
TI - Untargeted metabolomic analysis of tomato pollen development and heat stress
response.
AB - KEY MESSAGE: Pollen development metabolomics. Developing pollen is among the
plant structures most sensitive to high temperatures, and a decrease in pollen
viability is often associated with an alteration of metabolite content. Most of
the metabolic studies of pollen have focused on a specific group of compounds,
which limits the identification of physiologically important metabolites. To get
a better insight into pollen development and the pollen heat stress response, we
used a liquid chromatography-mass spectrometry platform to detect secondary
metabolites in pollen of tomato (Solanum lycopersicum L.) at three developmental
stages under control conditions and after a short heat stress at 38 degrees C.
Under control conditions, the young microspores accumulated a large amount of
alkaloids and polyamines, whereas the mature pollen strongly accumulated
flavonoids. The heat stress treatment led to accumulation of flavonoids in the
microspore. The biological role of the detected metabolites is discussed. This
study provides the first untargeted metabolomic analysis of developing pollen
under a changing environment that can serve as reference for further studies.
PMID- 28508931
TI - Kafka and Autism : The Undisclosed Logic Behind Kafka's Work.
AB - In this paper the hypothesis is presented that Franz Kafka was a person with
autism. This is done by analyzing and discussing his biography, letters, diaries
and major works. Kafka's autism is an integral diagnosis which encompasses both
his personal life and his work. This interpretation is contrary to other
interpretations from the past which in all cases were only partially applicable
to explain Kafka's life and work. In Kafka research the big secret of Kafka was
how he was able to write he did, like no one before him had done. The function
and use of parables are also discussed to support this autism hypothesis
concerning Franz Kafka which ultimately makes his life and work more
understandable and accessible.
PMID- 28508930
TI - Assessing Psychological Insulin Resistance in Type 2 Diabetes: a Critical
Comparison of Measures.
AB - PURPOSE OF REVIEW: This study aims to examine the operationalisation of
'psychological insulin resistance' (PIR) among people with type 2 diabetes and to
identify and critique relevant measures. RECENT FINDINGS: PIR has been
operationalised as (1) the assessment of attitudes or beliefs about insulin
therapy and (2) hypothetical or actual resistance, or unwillingness, to use to
insulin. Five validated PIR questionnaires were identified. None was fully
comprehensive of all aspects of PIR, and the rigour and reporting of
questionnaire development and psychometric validation varied considerably between
measures. Assessment of PIR should focus on the identification of negative and
positive attitudes towards insulin use. Actual or hypothetical insulin refusal
may be better conceptualised as a potential consequence of PIR, as its assessment
overlooks the attitudes that may prevent insulin use. This paper provides
guidance on the selection of questionnaires for clinical or research purpose and
the development of new, or improvement of existing, questionnaires.
PMID- 28508932
TI - Enterovirus-Related Immune Reconstitution Inflammatory Syndrome (IRIS) Following
Haploidentical Stem Cell Transplantation in an MHC Class II-Deficient Child.
PMID- 28508934
TI - Xanthomatous macrophages in bone marrow biopsies: systemic manifestation of
mycobacterioses.
PMID- 28508933
TI - Genetic Variants Within Key Nodes of the Cascade of Antipsychotic Mechanisms:
Effects on Antipsychotic Response and Schizophrenia Psychopathology in a
Naturalistic Treatment Setting in Two Independent Korean and Italian Samples.
AB - INTRODUCTION: Schizophrenia (SCZ) is one of the most disabling psychiatric
disorders. Genetic factors play an important role in both SCZ liability and its
treatment outcome. In the present paper, we investigated the effects of several
single nucleotide polymorphisms (SNPs) within ten strong candidate genes involved
with antipsychotics (APs) mechanisms of action. METHODS: Two independent samples
were investigated in the present study. Totals of 176 SCZ subjects and 326
controls of Korean ancestry, and 83 SCZ subjects and 194 controls of Italian
ancestry were recruited and genotyped. SCZ risk and other parameters were also
investigated. RESULTS: Concerning APs response, only a nominal association with
HOMER1 rs3822568 in the Korean sample was found. In the haplotype analysis,
rs9801117 C-rs12668837 C-rs4621754 A haplotype within ESYT2 and NCAPG2 genes was
associated with APs response in the same sample. As for secondary outcomes,
rs7439 within PKDCC and rs12668837 within NCAPG2 were associated with SCZ risk in
the Italian sample. In the haplotype analysis, rs2788478 G-rs2657375 T-rs1039621
A within the region between WDR60 and ESYT genes and rs2013 C (ESYT2)-rs6459896 A
(NCAPG2) haplotypes were associated with SCZ in the same sample. No association
was found in the Korean sample. Finally, our exploratory data suggest a possible
modulation of HOMER1, ARC, BDNF, TXNRD2, WDR60, and ESYT2 genes in the APs
response to specific symptom clusters. CONCLUSION: Our results did not support a
primary role for the genes investigated in the APs response. On the other hand,
our secondary results suggest a possible involvement of NACPG2 and PKDCC in SCZ
liability. Finally, our exploratory findings may deserve further investigations
in specific studies.
PMID- 28508935
TI - Successful treatment of calcineurin inhibitor-induced pain syndrome with acute
graft versus host disease by switching calcineurin inhibitors followed by
pregabalin.
PMID- 28508936
TI - Phase I Clinical Study of ZYAN1, A Novel Prolyl-Hydroxylase (PHD) Inhibitor to
Evaluate the Safety, Tolerability, and Pharmacokinetics Following Oral
Administration in Healthy Volunteers.
AB - OBJECTIVE: This phase I study of ZYAN1 was conducted to evaluate the safety,
tolerability, and pharmacokinetics following oral administration in healthy
volunteers. METHODS: The study was a randomized, double-blind, placebo-controlled
phase I study carried out in two parts in addition to a third part involving an
open-label study to evaluate the food/sex effect. A total of 100 subjects were
enrolled into the study as follows: part I-single-dose study with ZYAN1 10, 25,
50, 100, 150, 200, and 300 mg (n = 56); part II-multiple-dose study with every
other day dosing of ZYAN1 100, 150, 200, and 300 mg (n = 32); and part III-sex
and food effect study with ZYAN1 150 mg (n = 12; open-label). RESULTS: ZYAN1 was
well-tolerated after single and multiple oral ascending doses. No drug-related
serious adverse events were reported. Following a single ascending dose of ZYAN1,
the maximum concentration (C max) ranged from 566.47 +/- 163.03 to 17,858.33 +/-
2899.19 ng/mL and the median time to C max (t max) was approximately 2.5 h for
the studied 30-fold oral doses of ZYAN1. Regardless of single or multiple doses,
mean C max and area under the concentration-time curve from time zero to time t
(AUC t ) values generally showed a dose-proportional increase. The mean
elimination half-life (t 1/2) of ZYAN1 ranged from 6.9 to 13 h with negligible
accumulation. Following a single dose of ZYAN1, the mean serum erythropoietin
(EPO) C max values showed dose response (i.e., 6.6 and 79.9 mIU/L for 10 and 300
mg ZYAN1 doses, respectively), while the time to mean maximal serum EPO
concentrations ranged from 10 to 72 h. CONCLUSION: Oral single (10-300 mg) and
multiple dosing (100-300 mg) of ZYAN1 in healthy subjects was found to be safe
and well-tolerated. With increasing ZYAN1 dose, there was almost a proportional
increase in mean C max and AUC t . The mean serum EPO concentrations showed a
trend of dose response. Based on the t 1/2, pharmacodynamic activity, and lack of
drug accumulation, a once every 2 days dosing regimen of ZYAN1 was appropriate
for phase II study. TRIAL REGISTRATION: Australian New Zealand Clinical Trials
Registry trial ID ACTRN12614001240639.
PMID- 28508937
TI - The Prevalence of Oropharyngeal Dysphagia in Adults Presenting with
Temporomandibular Disorders Associated with Rheumatoid Arthritis: A Systematic
Review and Meta-analysis.
AB - Temporomandibular disorders (TMDs) are the most frequent non-dental orofacial
pain disorders and may be associated with rheumatoid arthritis (RA), resulting in
oropharyngeal dysphagia (OD). However, clinicians' understanding of involvement
with OD caused by RA-related TMDs is limited and the methodological quality of
research in this field has been criticised. Therefore, the aim of this study was
to systematically review the prevalence of oral preparatory and oral stage signs
and symptoms of OD in adults presenting with TMDs associated with RA. A
systematic review of the literature was completed. The following electronic
databases were searched from inception to February 2016, with no date/language
restriction: EMBASE, PubMed, CINAHL, Web of Science, Elsevier Scopus, Science
Direct, AMED, The Cochrane Database of Systematic Reviews, and ProQuest
Dissertations and Theses A & I. Grey literature and reference lists of the
included studies were also searched. Studies reporting the frequency of OD in
adults presenting with TMD and RA were included. Study eligibility and quality
were assessed by three independent reviewers. Methodological quality was assessed
using the Down's and Black tool. The search yielded 19 eligible studies. Typical
difficulties experienced by RA patients included impaired swallowing (24.63%),
impaired masticatory ability (30.69%), masticatory pain (35.58%), and masticatory
fatigue (21.26%). No eligible studies reported figures relating to the prevalence
of weight loss. Eligible studies were deemed on average to be of moderate
quality. Study limitations included the small number of studies which met the
inclusion criteria and the limited amount of studies utilising objective
assessments. Valid and reliable prospective research is urgently required to
address the assessment and treatment of swallowing difficulties in RA as TMJ
involvement may produce signs and symptoms of OD.
PMID- 28508939
TI - [The worlds of gods in medicine].
AB - BACKGROUND: A number of designations for diseases, medicines and human body
structures derive from classical mythology. To date, these eponyms have not been
systematically investigated. OBJECTIVES: This paper provides an overview of this
fringe component of medical vocabulary, looks at the history of several terms and
formulates hypotheses as to why such creative etymologies have come into being.
MATERIALS AND METHODS: In addition to relevant texts on ancient mythology, a
variety of medical textbooks from the early modern period were analyzed. RESULTS:
Between the 16th and the 20th centuries some 30 figures from Greek and Roman
literature made their way into the terminology of medical sciences. A few of
these expressions can be encountered in clinical use (e. g., Caput Medusae,
Proteus, Oedipus complex) and remain official anatomical (atlas, Achilles tendon)
or pharmaceutical nomenclature (atropine, morphine). The choice of these
designations has often been similarity of form or analogies in function.
Classical eponyms have gained acceptance on account of their succinctness,
conciseness and scholarly veneer. Finally, this vocabulary shares its origin with
other relevant terminology. CONCLUSIONS: In clinical classes, mythological
designations can serve as a point of departure for digressions into literary, art
and medical history in order to provide an understanding of cultural traditions
and enhance education.
PMID- 28508941
TI - [Unusual tumor of the kidney].
PMID- 28508938
TI - Immunotherapy for the Treatment of Uveal Melanoma: Current Status and Emerging
Therapies.
AB - PURPOSE OF REVIEW: Uveal melanoma is a distinct subset of melanoma with a biology
and treatment approach that is unique from that of cutaneous melanoma. Here we
will review the current data evaluating immunotherapies in both the adjuvant and
metastatic settings in uveal melanoma. RECENT FINDINGS: In the adjuvant setting,
interferon demonstrated no survival benefit in uveal melanoma, and studies
evaluating immune-based strategies such as vaccine therapy are ongoing. Anti-CTLA
4 and anti-PD-1/ PD-L1 blockade in uveal melanoma have been evaluated in several
small prospective and/or retrospective studies with rare responses and no overall
survival benefit demonstrated. Ongoing studies evaluating combination checkpoint
inhibition and other antibody-based therapies are ongoing. Although immunotherapy
with anti-CTLA-4 and anti-PD-1 agents has dramatically changed the treatment
approach to cutaneous melanoma, its success in uveal melanoma has been much more
limited. Clinical trial participation should be prioritized in patients with
uveal melanoma.
PMID- 28508942
TI - [Conservative and surgical ileus treatment].
AB - The diagnosis ileus is one of the most common indications for an emergency
laparotomy. In 70% of the cases, the small intestine is affected, and in 30% it
is the colorectum. While stuck hernias are a major cause in developing countries,
the most common causes in western countries are postoperative adhesions that lead
to an acute bowl obstruction. The timeframe for treatment of a complete
mechanical obstruction is short as acute ischemia can lead to necrosis with bowl
perforation within 6 h. The perioperative lethality for an emergency laparotomy
due to an ileus ranges from 5-15%. In addition to the mechanical ileus, primary
and secondary paralytic ileus is important in the differential diagnosis. As the
genesis of postoperative ileus is multifactorial, a multimodal concept is
required for successful treatment.
PMID- 28508944
TI - Suppressive effects of zingerone on TGFBIp-mediated septic responses.
AB - Zingerone (ZGR), a phenolic alkanone isolated from ginger, has been reported to
possess various pharmacological activities. Transforming growth factor beta
induced protein (TGFBIp) is an extracellular matrix protein whose expression in
several cell types is greatly increased by TGF-beta. TGFBIp is released by human
umbilical vein endothelial cells and functions as a mediator of experimental
sepsis. We hypothesized that ZGR could reduce TGFBIp-mediated severe inflammatory
responses in human endothelial cells and mice. Here, we investigated the anti
septic effects and underlying mechanisms of ZGR against TGFBIp-mediated septic
responses. ZGR effectively inhibited lipopolysaccharide-induced release of TGFBIp
and suppressed TGFBIp-mediated septic responses. In addition, ZGR suppressed
TGFBIp-induced sepsis lethality and pulmonary injury. In conclusion, ZGR
suppressed TGFBIp-mediated and CLP-induced septic responses. Therefore, ZGR could
be a potential therapeutic agent for treatment of various severe vascular
inflammatory diseases via inhibition of the TGFBIp signaling pathway.
PMID- 28508943
TI - Perceived ethnic discrimination in relation to smoking and alcohol consumption in
ethnic minority groups in The Netherlands: the HELIUS study.
AB - OBJECTIVES: We examined the associations of perceived ethnic discrimination (PED)
with smoking and alcohol consumption in ethnic minority groups residing in a
middle-sized European city. METHODS: Data were derived from the HELIUS study in
Amsterdam, The Netherlands. We included 23,126 participants aged 18-70 years of
Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish, and
Moroccan origin. We collected self-reported data on PED, current smoking, heavy
smoking, nicotine dependence, current drinking, excessive drinking, and alcohol
dependence. Logistic regression was used. RESULTS: In general, we observed
positive associations in participants of African Surinamese and Ghanaian origin,
but no associations in those of South-Asian Surinamese, Turkish, or Moroccan
origin. In African Surinamese, the associations were positive for current
smoking, nicotine, and alcohol dependence (odds ratios of 1.16; 95% confidence
interval: 1.06-1.27, 1.34; 1.15-1.57 and 1.40; 1.20-1.64, respectively). In
Ghanaians, positive association was observed for current drinking (1.21; 1.08
1.36). CONCLUSIONS: The associations of PED with smoking and alcohol consumption
considerably varied by ethnicity and outcome measure. This suggests that ethnic
minority groups in Europe might use different behavioural strategies to cope with
PED.
PMID- 28508946
TI - Using principal component analysis and annual seasonal trend analysis to assess
karst rocky desertification in southwestern China.
AB - Increasing exploitation of karst resources is causing severe environmental
degradation because of the fragility and vulnerability of karst areas. By
integrating principal component analysis (PCA) with annual seasonal trend
analysis (ASTA), this study assessed karst rocky desertification (KRD) within a
spatial context. We first produced fractional vegetation cover (FVC) data from a
moderate-resolution imaging spectroradiometer normalized difference vegetation
index using a dimidiate pixel model. Then, we generated three main components of
the annual FVC data using PCA. Subsequently, we generated the slope image of the
annual seasonal trends of FVC using median trend analysis. Finally, we combined
the three PCA components and annual seasonal trends of FVC with the incidence of
KRD for each type of carbonate rock to classify KRD into one of four categories
based on K-means cluster analysis: high, moderate, low, and none. The results of
accuracy assessments indicated that this combination approach produced greater
accuracy and more reasonable KRD mapping than the average FVC based on the
vegetation coverage standard. The KRD map for 2010 indicated that the total area
of KRD was 78.76 * 103 km2, which constitutes about 4.06% of the eight southwest
provinces of China. The largest KRD areas were found in Yunnan province. The
combined PCA and ASTA approach was demonstrated to be an easily implemented,
robust, and flexible method for the mapping and assessment of KRD, which can be
used to enhance regional KRD management schemes or to address assessment of other
environmental issues.
PMID- 28508945
TI - Clinical efficacy of percutaneous cryoablation combined with allogenic NK cell
immunotherapy for advanced non-small cell lung cancer.
AB - In this study, the safety and clinical efficacy of cryosurgery combined with
allogenic NK cell immunotherapy for the treatment of advanced non-small cell lung
cancer (NSCLC) were evaluated. From July 2016 to March 2017, we enrolled 60
patients who met the enrollment criteria and divided them into two groups: (1)
the simple cryoablation group (n = 30) and (2) the cryoablation combined with
allogenic NK cell group (n = 30). The changes in immune function, quality of
life, and clinical response were evaluated. We found that allogenic NK cells
combined with cryosurgical treatment for advanced NSCLC have a synergistic
effect, which not only enhancing the immune function of patients, improving the
quality of life, and significantly increasing the response rate (RR) and disease
control rate (DCR) compared to cryoablation group. This study is the first
clinical trial of allogenic NK cells combined with cryosurgery for the treatment
of advanced NSCLC and preliminaily its safety and efficacy.
PMID- 28508949
TI - Zn(II)-dipicolylamine-based metallo-lipids as novel non-viral gene vectors.
AB - In this study, a series of Zn(II)-dipicolylamine (Zn-DPA) based cationic lipids
bearing different hydrophobic tails (long chains, alpha-tocopherol, cholesterol
or diosgenin) were synthesized. Structure-activity relationship (SAR) of these
lipids was studied in detail by investigating the effects of several structural
aspects including the type of hydrophobic tails, the chain length and saturation
degree. In addition, several assays were used to study their interactions with
plasmid DNA, and results reveal that these lipids could condense DNA into
nanosized particles with appropriate size and zeta-potentials. MTT-based cell
viability assays showed that lipoplexes 5 had low cytotoxicity. The in vitro gene
transfection studies showed the hydrophobic tails clearly affected the TE, and
hexadecanol-containing lipid 5b gives the best TE, which was 2.2 times higher
than bPEI 25k in the presence of 10% serum. The results not only demonstrate that
these lipids might be promising non-viral gene vectors, but also afford us clues
for further optimization of lipidic gene delivery materials.
PMID- 28508947
TI - Podocytes from the diagnostic and therapeutic point of view.
AB - The central role of podocytes in glomerular diseases makes this cell type an
interesting diagnostic tool as well as a therapeutic target. In this review, we
discuss the current literature on the use of podocytes and podocyte-specific
markers as non-invasive diagnostic tools in different glomerulopathies.
Furthermore, we highlight the direct effects of drugs currently used to treat
primary glomerular diseases and describe their direct cellular effects on
podocytes. A new therapeutic potential is seen in drugs targeting the podocytic
actin cytoskeleton which is essential for podocyte foot process structure and
function. Incubation of cultured human podocyte cell lines with sera from
patients with active glomerular diseases is currently also used to identify novel
circulating factors with pathophysiological relevance for the glomerular
filtration barrier. In addition, treatment of detached urinary podocytes from
patients with substances that restore their cytoskeleton might serve as a novel
personalized tool to estimate their potential for podocyte recovery ex vivo.
PMID- 28508950
TI - Malignancy as a comorbidity in rheumatic diseases: a retrospective hospital-based
study.
AB - Patients with Rheumatic diseases (RDs) are at an increased risk of malignancies
compared with the general population. The aim of this study was to examine the
relative frequency of several cancers in a single homogeneous cohort of patients
with different RDs. Patients diagnosed with rheumatoid arthritis (RA), Ankylosing
spondylitis (AS), Sjogren's syndrome (SS), systemic lupus erythematosus (SLE),
systemic sclerosis (SSc), dermatomyositis (DM), or polymyositis were included.
Out of 3982 adult residents admitted to the division of rheumatology, 61
malignancies were observed. The 2009 National Central Cancer Registry (NCCR) of
China served as the reference for calculating standardized ratio (SR). The
malignancy frequency had no difference between RDs with malignancy and the
general population. Patients with SS and DM/PM showed an increased risk of non
Hodgkin's lymphoma (SR for SS patients = 9.709, 95% confidence interval (CI) =
4.602 to 17.916; SR for DM/PM = 35.714, 95% CI = 25.001 to 49.527). Patients with
DM/PM and SSc showed an increased risk of lung cancer (SR for DM/PM = 10.638, 95%
CI = 5.245 to 19.131; SR for SSc patients = 7.752, 95% CI = 3.295 to 15.309).
Patients with SS and DM/PM showed an increased risk of ovary cancer (SR for SS
patients = 8.177, 95% CI = 3.566 to 15.888; SR for DM/PM = 32.258, 95% CI =
22.126 to 45.490). Patients with SLE showed an increased risk of cervix cancer
(SR for AS patients = 6.897, 95% CI = 2.748 to 14.144). Patients with AS showed
an increased risk of pancreas cancer (SR for AS patients = 7.576, 95% CI = 2.181
to 15. 071). Different RDs have an increased risk of particular cancers. Among
hematologic cancers, the risk of non-Hodgkin's lymphoma was higher than general
population. Among solid tumors, the risk of cancers of the lung, ovary, cervix,
and pancreas was higher than general population.
PMID- 28508951
TI - Magnesium ions enhance infiltration of osteoblasts in scaffolds via increasing
cell motility.
AB - Magnesium (Mg) ions are the most abundant intracellular divalent cations and play
a pivotal role in numerous cellular processes. Biodegradable Mg-containing
materials, including scaffolds, are promising candidates for orthopedic
applications. Here, we investigated the effect of Mg ions on the cellular
properties of osteoblasts. Cytotoxicity tests on osteoblasts confirmed that no
cytotoxic effects were found up to a supplementing Mg ion concentration of 10 mM.
Mg ions at a concentration of 5 mM increased the migration and invasiveness of
osteoblasts. To investigate the stimulatory effect of Mg ions on cell motility in
scaffolds, we fabricated 10 wt% Mg ion-containing polycaprolactone (PCL)
scaffolds, using the wire-network molding (WNM) technique. Mg ion-containing
scaffolds persistently released Mg ions at a concentration of 5 mM in the media
after pre-incubation. Furthermore, increased cell motility was confirmed in Mg
ion-containing scaffolds by quantification of genomic DNA and protein content.
Our results provide an important basis for the function of Mg ions and their
effect on cell motility, and propose a novel role for Mg ions in scaffold
applications.
PMID- 28508952
TI - Identification of Sex-determining Loci in Pacific White Shrimp Litopeneaus
vannamei Using Linkage and Association Analysis.
AB - The Pacific white shrimp Litopenaeus vannamei is a predominant aquaculture shrimp
species in the world. Like other animals, the L. vannamei exhibited sexual
dimorphism in growth trait. Mapping of the sex-determining locus will be very
helpful to clarify the sex determination system and further benefit the shrimp
aquaculture industry towards the production of mono-sex stocks. Based on the data
used for high-density linkage map construction, linkage-mapping analysis was
conducted. The sex determination region was mapped in linkage group (LG) 18. A
large region from 0 to 21.205 cM in LG18 showed significant association with sex.
However, none of the markers in this region showed complete association with sex
in the other populations. So an association analysis was designed using the
female parent, pool of female progenies, male parent, and pool of male progenies.
Markers were de novo developed and those showing significant differences between
female and male pools were identified. Among them, three sex-associated markers
including one fully associated marker were identified. Integration of linkage and
association analysis showed that the sex determination region was fine-mapped in
a small region along LG18. The identified sex-associated marker can be used for
the sex detection of this species at genetic level. The fine-mapped sex
determining region will contribute to the mapping of sex-determining gene and
help to clarify sex determination system for L. vannamei.
PMID- 28508953
TI - [Mycotoxins in food : Occurrence, importance and health risk].
AB - Mycotoxins are produced by a variety of fungal species on crops or stored
commodities; they appear as primary or secondary contaminants and via the
carryover effect in the food chain. The global occurrence of many mycotoxins with
a wide spectrum of toxicities is the subject of interdisciplinary research and a
relevant topic for consumer protection. This overview aims to raise interest with
sections of the hazardous properties of important mycotoxins (from aflatoxin to
zearalenone) and describes recent developments in the area of exposure assessment
and basic principles applied in risk characterization. Challenges with regard to
new insights about modified and so far unregulated mycotoxins are also addressed.
PMID- 28508954
TI - [Perceived risks of food contaminants].
AB - BACKGROUND: Food contaminants can pose a serious health threat. In order to carry
out adequate risk communication measures, the subjective risk perception of the
public must be taken into account. In this context, the breadth of the topic and
insufficient terminological delimitations from residues and food additives make
an elaborate explanation of the topic to consumers indispensable. A
representative population survey used language adequate for lay people and a
clear definition of contaminants to measure risk perceptions with regard to food
contaminants among the general public. OBJECTIVES: The study aimed to assess
public awareness of contaminants and the perceived health risks associated with
them. In addition, people's current knowledge and need for additional
information, their attitudes towards contaminants, views on stakeholder
accountability, as well as compliance with precautionary measures, such as
avoiding certain foods to reduce health risks originating from contaminants, were
assessed. MATERIALS AND METHODS: A representative sample of 1001 respondents was
surveyed about food contaminants via computer-assisted telephone interviewing.
RESULTS: The majority of respondents rated contaminants as a serious health
threat, though few of them spontaneously mentioned examples of undesirable
substances in foods that fit the scientific or legal definition of contaminants.
Mercury and dioxin were the most well-known contaminants. Only a minority of
respondents was familiar with pyrrolizidine alkaloids. CONCLUSIONS: The present
findings highlight areas that require additional attention and provide
implications for risk communication geared to specific target groups.
PMID- 28508955
TI - [How does a pesticide residue turn into a contaminant?]
AB - Over the last few years pesticide residues have been repeatedly detected during
official food controls that would not be expected from authorized pesticide uses.
These residues do not always pose a health risk for consumers. However, the legal
and economic consequences of such findings are often far-reaching, especially if
the admissible maximum residue limits have been fixed at the LOQ level only. For
some example cases, we discuss the real entry pathways into the food chain and
under which circumstances residues of such unintentionally added substances could
be better regulated under the contaminant legal framework rather than the
pesticide legal framework.
PMID- 28508956
TI - Doctors' attitudes towards the introduction and clinical operation of do not
resuscitate orders (DNRs) in Ireland.
AB - BACKGROUND: Do not resuscitate orders (DNRs) are documents which state that
should a patient suffer from cardiopulmonary failure, resuscitation should not be
attempted. Internationally, DNRs are often misunderstood and used inappropriately
in a clinical setting. AIMS: The aim of this paper was to determine the current
understanding of DNRs and their clinical operation among hospital doctors in
Ireland. METHODS: A cross-sectional, questionnaire-based study was conducted
involving doctors from the Cork teaching hospitals. The questionnaire sought
information regarding understanding of DNRs and their clinical operation, as well
as attitudes regarding the current absence of relevant Irish guidelines. The
questionnaire also collected information regarding demographics, clinical
specialty, and level of experience. RESULTS: 45.9% (47/103) of all doctors stated
that their clinical knowledge was sufficient to draft a DNR, but 48.7% of this
group (n = 23) chose the incorrect definition for a DNR when provided with three
separate options. Thirty-five percent (n = 36) of all doctors surveyed
demonstrated an incorrect understanding of a DNR. Neither specialty nor
experience level had any effect on level of understanding of DNRs (p > 0.05).
93.2% (n = 96) agreed that there is a need for introduction of domestic
guidelines regarding DNRs. 57.6% (n = 59) would draft more DNRs in the event that
such domestic guidelines were in place. CONCLUSIONS: A substantial proportion of
hospital doctors surveyed demonstrated an incomplete understanding of DNRs and
their clinical operation. However, the overwhelming majority of the present
sample believe that domestic guidelines are needed on the matter.
PMID- 28508958
TI - Modeling the critical care pathway for cardiothoracic surgery.
AB - The west of Scotland heart and lung center based at the Golden Jubilee National
Hospital houses all adult cardiothoracic surgery for the region. Increased demand
for scheduled patients and fluctuations in emergency referrals resulted in
increasing waiting times and patient cancellations. The main issue was limited
resources, which was aggravated by the stochastic nature of the length of stay
(LOS) and arrival of patients. Discrete event simulation (DES) was used to assess
if an enhanced schedule was sufficient, or more radical changes, such as capacity
or other resource reallocations should be considered in order to solve the
problem. Patients were divided into six types depending on their condition and
LOS at the different stages of the process. The simulation model portrayed each
patient type's pathway with sufficient detail. Patient LOS figures were analyzed
and distributions were formed from historical data, which were then used in the
simulation. The model proved successful as it showed figures that were close to
actual observations. Acquiring results and knowing exactly when and what caused a
cancellation was another strong point of the model. The results demonstrated that
the bottleneck in the system was related to the use of High Dependency Unit (HDU)
beds, which were the recovery beds used by most patients. Enhancing the schedule
by leveling out the daily arrival of patients to HDUs reduced patient
cancellations by 20%. However, coupling this technique with minor capacity
reallocations resulted in more than 60% drop in cancellations.
PMID- 28508957
TI - Genetic and environmental correlations between subjective wellbeing and
experience of life events in adolescence.
AB - Some life events appear heritable due to the genetic influence on related
behaviours. Shared genetic influence between negative behaviours and negative
life events has previously been established. This study investigated whether
subjective wellbeing and positive life events were genetically associated.
Participants in the Twins Early Development Study (aged 16.32 +/- .68 years)
completed subjective wellbeing and life events assessments via two separate
studies (overlapping N for wellbeing and life events measures ranged from 3527 to
9350). We conducted bivariate twin models between both positive and negative life
events with subjective wellbeing and related positive psychological traits
including subjective happiness, life satisfaction, optimism, hopefulness and
gratitude measured at 16 years. Results suggested that the heritability of life
events can partially be explained by shared genetic influences with the wellbeing
indicators. Wellbeing traits were positively genetically correlated with positive
life events and negatively correlated with negative life events (except curiosity
where there was no correlation). Those positive traits that drive behaviour (grit
and ambition) showed the highest genetic correlation with life events, whereas
the reflective trait gratitude was less correlated. This suggests that gene
environment correlations might explain the observed genetic association between
life events and wellbeing. Inheriting propensity for positive traits might cause
you to seek environments that lead to positive life events and avoid environments
which make negative life events more likely.
PMID- 28508959
TI - Surgical treatment of patellar instability: clinical and radiological outcome
after medial patellofemoral ligament reconstruction and tibial tuberosity
medialisation.
AB - INTRODUCTION: The aim of this retrospective study was to analyse clinical and
radiological outcome after medial patellofemoral ligament reconstruction (MPFLR)
and tibial tuberosity medialisation (TTM) in patients with recurrent patellar
instability. MATERIALS AND METHODS: Thirty-five patients were included between
2008 and 2012. According to defined criteria such as tibial tuberosity-trochlear
groove (TTTG) distance, hyperpression on the lateral patella facet and lateral
retropatellar cartilage damage either MPFLR (group A) or TTM (group B) was
performed: 18 patients underwent TTM, the other 17 patients underwent MPFLR. At a
mean of 25.4 +/- 9.7 (group A) and 35.2 +/- 17.6 months (group B) patients were
clinically and radiologically reviewed. Validated knee scores such as Kujala,
Lysholm and Tegner score were evaluated. RESULTS: In both groups one patient
reported of a non-traumatic patellar redislocation. Patients who underwent MPFLR
(group A) had less pain postoperatively during activity according to the Visual
Analogue Scale (group A: 2.0 +/- 2.1 points, group B: 3.9 +/- 2.3 points).
Retropatellar cartilage damage increased in group B from grade 1 (range: 1-3)
preoperatively to grade 2 (range 1-3) postoperatively (p > 0.05). All other
clinically evaluated items, as well as the applied knee scoring systems,
indicated no significant difference (p > 0.05) and displayed good to excellent
results. CONCLUSIONS: MPFLR and TTM leed to good clinical results despite its own
indications. For this reason-in selected cases-TTM may still be a suitable
procedure for surgical treatment of patellar instability. However, patients
treated by TTM (group B) revealed an increased retropatellar cartilage damage as
well as significantly more pain during activity.
PMID- 28508961
TI - Bacteremic kidney cyst infection caused by Helicobacter cinaedi.
AB - Cyst infection is one of the major complications in patients with autosomal
dominant polycystic kidney disease (ADPKD). The causative pathogen in kidney cyst
infection frequently goes undetected. Although only one case report of kidney
cyst infection caused by Helicobacter cinaedi (H. cinaedi) is published in
English literature, it may be an important pathogen in kidney cyst infection.
Kidney cyst infection and H. cinaedi infection share the common characteristic of
tendency to relapse and chronic kidney disease is a major risk factor for H.
cinaedi infection. Moreover, a long period is required to detect H. cinaedi in
blood cultures, potentially causing false-negative results. After the
identification of H. cinaedi, we must carefully select antibiotics and the
antibiotic treatment period should be extended to prevent recurrence. Here we
present a case of a 58-year-old male with ADPKD who developed bacteremic kidney
cyst infection caused by H. cinaedi. He was admitted to our hospital because of
fever, lower left back pain, vomiting, and feeling of abdominal enlargement. H.
cinaedi was detected from the blood cultures obtained at admission after 4 days
of culture. Antibiotics were administered for 8 weeks after confirming negative
blood cultures. There was no evidence of kidney cyst infection relapse at 3
months after treatment completion. Nephrologists should regard H. cinaedi as a
challenging but important pathogen in kidney cyst infection, particularly when
the causative organism is unknown or kidney cyst infection is recurrent.
PMID- 28508962
TI - Proteinuria rebound in IgA nephropathy associated with obesity-related
glomerulopathy.
AB - IgA nephropathy (IgAN), the most prevalent primary chronic glomerulonephritis
worldwide, has three major risk factors: hypertension, proteinuria >1 g/day, and
severe renal lesions. Obesity also portends a poor prognosis. A Japanese boy with
IgAN showed nephrotic syndrome at presentation. Pathological features resembled
those of membranoproliferative glomerulonephritis (MPGN), although IgA deposition
differed from MPGN and IgAN. Combination therapy improved renal lesions, but
rebound deterioration of proteinuria occurred in this patient, who had marked
obesity and hypertension. Serial kidney biopsy specimens were compatible with
obesity-related glomerulopathy (ORG). Rebound proteinuria was apparently
attributable to ORG rather than relapse and flaring up of IgAN.
PMID- 28508960
TI - Impairment of pH gradient and membrane potential mediates redox dysfunction in
the mitochondria of the post-ischemic heart.
AB - The mitochondrial electrochemical gradient (Deltap), which comprises the pH
gradient (DeltapH) and the membrane potential (DeltaPsi), is crucial in
controlling energy transduction. During myocardial ischemia and reperfusion (IR),
mitochondrial dysfunction mediates superoxide (.O2-) and H2O2 overproduction
leading to oxidative injury. However, the role of DeltapH and DeltaPsi in post
ischemic injury is not fully established. Here we studied mitochondria from the
risk region of rat hearts subjected to 30 min of coronary ligation and 24 h of
reperfusion in vivo. In the presence of glutamate, malate and ADP, normal
mitochondria (mitochondria of non-ischemic region, NR) exhibited a heightened
state 3 oxygen consumption rate (OCR) and reduced .O2- and H2O2 production when
compared to state 2 conditions. Oligomycin (increases DeltapH by inhibiting ATP
synthase) increased .O2- and H2O2 production in normal mitochondria, but not
significantly in the mitochondria of the risk region (IR mitochondria or post
ischemic mitochondria), indicating that normal mitochondrial .O2- and H2O2
generation is dependent on DeltapH and that IR impaired the DeltapH of normal
mitochondria. Conversely, nigericin (dissipates DeltapH) dramatically reduced .O2
and H2O2 generation by normal mitochondria under state 4 conditions, and this
nigericin quenching effect was less pronounced in IR mitochondria. Nigericin also
increased mitochondrial OCR, and predisposed normal mitochondria to a more
oxidized redox status assessed by increased oxidation of cyclic hydroxylamine, CM
H. IR mitochondria, although more oxidized than normal mitochondria, were not
responsive to nigericin-induced CM-H oxidation, which is consistent with the
result that IR induced DeltapH impairment in normal mitochondria. Valinomycin, a
K+ ionophore used to dissipate DeltaPsi, drastically diminished .O2- and H2O2
generation by normal mitochondria, but less pronounced effect on IR mitochondria
under state 4 conditions, indicating that DeltaPsi also contributed to .O2-
generation by normal mitochondria and that IR mediated DeltaPsi impairment.
However, there was no significant difference in valinomycin-induced CM-H
oxidation between normal and IR mitochondria. In conclusion, under normal
conditions the proton backpressure imposed by DeltapH restricts electron flow,
controls a limited amount of .O2- generation, and results in a more reduced
myocardium; however, IR causes DeltapH impairment and prompts a more oxidized
myocardium.
PMID- 28508963
TI - Hemodiafiltration for hepatic encephalopathy induced by Budd-Chiari syndrome in a
patient with end-stage kidney disease.
AB - A 36-year-old woman who was undergoing dialysis for end-stage kidney disease
(ESKD) was admitted to our hospital with consciousness disorder. She was
diagnosed with Budd-Chiari syndrome due to antiphospholipid syndrome at the age
of 28 years. Her kidney function and leg edema gradually deteriorated. After
initiation of hemodialysis (HD), transient loss of consciousness due to hepatic
encephalopathy during HD treatment occurred frequently. Her kidney replacement
therapy was changed to online hemodiafiltration (HDF), which dramatically
improved her hepatic coma. Compared with HD, HDF contributed to the increase in
Fischer's ratio and decrease in tryptophan level, which has a high protein-bound
property. This case suggests that HDF may be beneficial for hepatic
encephalopathy in ESKD patients by modulating the amino acid profile.
PMID- 28508964
TI - TMEM67 mutations found in a case of Joubert syndrome with renal hypodysplasia.
AB - Joubert syndrome is a rare inherited cerebellar ataxia with the dysgenesis of the
cerebellar vermis, called the molar tooth sign. The combination of a large number
of causative genes, more than 27, and the various clinical features involving
multiple organs has established many genotypic-phenotypic correlations in Joubert
syndrome. TMEM67 is one of the genes that are relatively well established as
contributing to Joubert syndrome with liver involvement. Here, we report a 2
month-old boy who was initially treated for urinary tract infection, which
further led to the diagnosis of Joubert syndrome accompanied by renal
hypodysplasia with two different mutations: c.2522A>C and c.1065 + 4Adel in
TMEM67.
PMID- 28508965
TI - Cinacalcet in hyperparathyroidism management after pediatric renal
transplantation.
AB - Secondary hyperparathyroidism is often associated with end stage renal disease;
even after renal transplantation, hyperparathyroidism may persist, and is
responsible for hypercalcemia, hypophosphatemia and elevated parathyroid hormone
(iPTH) levels. Parathyroid hyperplasia is frequently associated with persistent
hyperparathyroidism, and may require a surgical treatment. Here, we report
hyperparathyroidism along with parathyroid hyperplasia in a 7-year-old child,
which persisted after renal transplant. Calcitonin and pamidronate failed to
decrease serum calcium levels; clodronate was also inefficient. Cinacalcet
therapy normalized serum calcium and phosphorus levels, and decreased iPTH levels
in 3 months; a severe parathyroid hyperplasia was also corrected under
calcimimetic therapy. In conclusion, we report in a child that hypercalcemia
associated with secondary hyperparathyroidism can be corrected with cinacalcet
after pediatric renal transplantation. We also show that parathyroid hyperplasia
can regress under calcimimetic therapy in a transplanted child, making surgery
unnecessary.
PMID- 28508966
TI - Recurrent purple urine bag syndrome presenting with full spectrum of disease
severity: case report and review of literature.
AB - Purple urine bag syndrome (PUBS) is a unique phenomenon characterized by purple
discoloration of the urinary catheter bag and tubing following urinary
catheterization lasting for hours to days. The purple discoloration is a mixture
of indirubin dissolved in plastic with indigo on its surface. PUBS is most
commonly associated with urinary tract infection (UTI) caused by bacteria with
indoxyl phosphatase/sulfatase activity. It occurs predominantly in chronically
catheterized, constipated elderly female patients. It usually appears to be
asymptomatic and harmless, but rarely it can present as a severe illness. We
report on a 29-year-old female with urinary ileal diversion presenting with
multiple episodes of PUBS each with an asymptomatic state of varying severity,
symptomatic UTI and severe sepsis requiring intensive care. To our knowledge,
this is the first report where a single young patient had recurrent PUBS which
presented with a full spectrum of disease severity at different occasions.
PMID- 28508967
TI - A case of xanthinuria type I with a novel mutation in xanthine dehydrogenase.
AB - Hereditary hypouricemia is generally caused by renal hypouricemia, an autosomal
recessive disorder that is characterized by impaired renal tubular uric acid
transport, or by xanthinuria, a rare autosomal recessive disorder caused by a
deficiency of xanthine dehydrogenase (XDH; xanthinuria type I) or by a deficiency
of both XDH and aldehyde oxidase (xanthinuria type II). In contrast to renal
hypouricemia, which sometimes leads to exercise-induced acute kidney injury
(EIAKI), xanthinuria has not been associated with this disorder. We report here a
case of xanthinuria type I due to a compound heterozygous mutation. A 46-year-old
woman was found to have undetectable plasma and urinary levels of uric acid. She
had no symptoms and no history of EIAKI. Xanthinuria type I was diagnosed
following the allopurinol loading test. Mutation analysis revealed a compound
heterozygous mutation [c.305A>G (p.Gln102Arg) and c.2567delC (p.Thr856Lysfs*73)]
in the XDH gene. Of these two mutations, the former is novel. The patient did not
exhibit EIAKI. However, because xanthinuria is a rare disease, the identification
of additional cases is necessary to determine whether this disease is complicated
with EIAKI.
PMID- 28508968
TI - Dialysis disequilibrium leading to posterior reversible encephalopathy syndrome
in chronic renal failure.
AB - Dialysis disequilibrium syndrome is a neurological adverse effect of acute
hemodialysis in advanced uremic patients. Dialysis disequilibrium has a wide
spectrum of clinical manifestations starting from subtle uneasiness, confusion,
to florid and complex life threatening neurological deficit. In this case study,
we present a patient who developed sudden cortical blindness following
hemodialysis due to posterior reversible encephalopathy, which is a rare
presentation of dialysis disequilibrium syndrome.
PMID- 28508969
TI - Five-year follow-up of a case of lipoprotein glomerulopathy with APOE Kyoto
mutation.
AB - We report the case of a 34-year-old Japanese male with lipoprotein glomerulopathy
(LPG). Renal biopsy showed LPG, and followed by a genetic analysis revealed a
mutation in apolipoprotein E gene (APOE Kyoto; Arg25Cys). We started treatment
with probucol, bezafibrate, losartan, and allopurinol. Urinary protein decreased
in response to treatment but has remained at about 1.27 +/- 0.71 g/gCr, and a
repeat biopsy which was performed 1 year after the first biopsy showed no clear
evidence of pathological remission and complication of other glomerular disease.
After 5 years of follow-up after the start of treatment, renal function has
almost maintained without apparent deterioration. Interestingly, the course of
the urinary protein level closely paralleled his triglyceride and cholesterol
levels in a long-term. This observation suggests the importance of tight control
of lipid profiles as a means of renoprotection in LPG patient.
PMID- 28508970
TI - Glomerulopathy with distinctive fibrillar deposits but lacking glomerular
deposition of type III collagen.
AB - A 62-year-old woman with nephrotic syndrome underwent a renal biopsy. Under light
microscopy, the biopsy findings included lobulation and enlargement of glomeruli,
occasional thickening of glomerular capillary walls, and narrowing of the
capillary lumen by swollen endothelial cells. Congo red staining was negative for
amyloid. No significant intraglomerular fibrin deposition was found by
phosphotungstic acid hematoxylin staining. Immunofluorescence microscopy showed
no deposition of immunoglobulin G, A, or M; no kappa or lambda light chains; and
no C3 or C1q. Electron microscopy revealed distinctive subendothelial and
mesangial fibrillar deposits, mesangial cell interposition, and swelling and
vacuolization of endothelial cells resulting in capillary lumen narrowing.
Although some curvilinear fibrillar deposits mimicked the bundles of type III
collagen fibers seen in collagenofibrotic glomerulopathy, neither glomerular
deposition of type III collagen nor elevation of serum procollagen III peptide
was noted. This glomerulopathy does not fulfill any known disease entities with
non-amyloid non-immunoglobulin-derived organized glomerular deposits.
PMID- 28508971
TI - Short-term outcome and quality of life in kidney transplant recipient with
monoclonal gammopathy.
AB - Monoclonal gammopathy of undetermined significance (MGUS) is the common pre
malignant B cell disorders with a general prevalence of 3-5 % at age over 50.
Because of the potential malignant transformation and immune insufficiency, pre
transplant MGUS recipient should be carefully followed after allograft
transplantation. The post-transplant prognosis and quality of life (QOL) in
patient with MGUS have not yet been fully determined. The aim of this study is to
evaluate function and pathology of the renal allograft and self-assessment QOL
changes during 2 years after transplantation in our case of MGUS-bearing
recipient. We here studied the clinical course and QOL improvement before and 20
months after transplant in a 56-year-old woman, who had pre-existing MGUS and
underwent living donor kidney transplantation. After the renal allograft
transplant, the patients maintained normal GFR and had neither acute rejections
nor histologic evidence of renal injuries related to the monoclonal gammopathy on
the protocol biopsy of 1 year post-transplant. During further 20 months follow
up, the pre-transplant MGUS remained uneventful without any hematologic
abnormalities and other medical complications, i.e., infection. Evaluation of QOL
using a self-assessment questionnaire showed significant improvement for physical
and mental items on both 6 and 18 months post-transplant. The renal transplant
thus successfully provided a greater satisfaction for the recipient on both
physical and mental health aspects. Our observations suggest that renal
transplantation is beneficial even in those who had pre-existing MGUS if managed
and followed carefully, which ultimately could significantly improve the patient
QOL.
PMID- 28508972
TI - Development of intracerebral hemorrhage in the short-term clinical course of a
patient with microscopic polyangiitis without neurological symptoms at diagnosis:
an autopsy case.
AB - A 77-year-old man with high-grade fever, progressive renal dysfunction, high
serum level of C-reactive protein and positive serum myeloperoxidase anti
neutrophil cytoplasmic antibody (MPO-ANCA) was diagnosed with microscopic
polyangiitis with rapidly progressive glomerulonephritis, and remission induction
treatment with glucocorticoids and intravenous cyclophosphamide was initiated.
Although his general condition improved in a short time, intracerebral hemorrhage
occurred 12 days after the initiation of treatment and emergent hematoma
evacuation was performed. However, he passed away on day 14. Surprisingly, even
though no clinical findings for any organs except for renal involvement was
detected before his death, autopsy revealed necrotizing vasculitis affecting
various systemic organs including kidney, pancreas, liver, myocardium in
ventricle, adipose tissue of the left adrenal gland, small intestine,
gallbladder, bronchus, prostate, testis and spleen. It is difficult to detect
widespread vasculitis without clinical symptoms and signs in patients with ANCA
associated vasculitis. A whole body assessment tool is necessary to detect
unexpected vital organ damage, including cerebral vessels.
PMID- 28508973
TI - Phlegmasia cerulean dolens: complication of femoral vein catheterization.
AB - There are three less frequent manifestations of acute massive venous thrombosis
and obstruction of the venous drainage of an extremity. They are phlegmasia alba
dolens, phlegmasia cerulean dolens (PCD), and venous gangrene. The term PCD
differentiates ischemia-associated massive venous thrombosis from phlegmasia alba
dolens, which describes fulminant venous thrombosis without ischemia. We present
a 55-year-old hypertensive, who presented with paedal oedema and breathlessness
at rest. About a month prior to this admission, she suffered dislocation of left
patella. She was treated with a plaster cast and immobilization for 3 weeks. Her
serum creatinine was 8.8 mg/dL. She was initiated on haemodialysis via two single
lumen catheters placed in left femoral vein. The femoral vein catheters were
removed after third session of haemodialysis. On fourth day, the patient
complained pain and blue discolouration of left toes. On examination, the left
lower limb was swollen, discoloured, and cold with blebs up to upper one-third of
left leg. The left dorsalis pedis and posterior tibial arteries were not
palpable. A Doppler of veins of lower limb revealed, thrombosis of deep, and
superficial venous system of left lower limb. As there was no response to
anticoagulation below, knee amputation was performed.
PMID- 28508974
TI - Pauci-immune crescentic glomerulonephritis associated with use of trimethoprim
sulfamethoxazole.
AB - Drug-induced pauci-immune crescentic glomerulonephritis has been described with
several agents, including propylthiouracil, minocycline, D-penicillamine, and
hydralazine. We present the case of a 60-year-old man who presented with rapidly
progressive glomerulonephritis in the setting of recent use of trimethoprim
sulfamethoxazole complicated by the development of the Stevens-Johnson syndrome,
and was found to have biopsy-proven pauci-immune crescentic glomerulonephritis
and undetectable anti-neutrophilic cytoplasmic antibodies. We review the existing
literature on the potential association between sulfonamides and hypersensitivity
polyangiitis.
PMID- 28508975
TI - A case of acquired lecithin:cholesterol acyltransferase deficiency with
sarcoidosis that remitted spontaneously.
AB - Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is a rare
inherited disorder that causes an extremely low high-density lipoprotein
cholesterol concentration in serum. Recently, acquired LCAT deficiency caused by
IgG antibodies to LCAT, without any LCAT gene mutation, was reported. Here we
describe a case of acquired LCAT deficiency occurring in association with
sarcoidosis. The patient was a Japanese female aged 70 years, had no mutation in
the LCAT gene exon sequence, but had an LCAT inhibitor factor in her serum,
detected using lipoprotein-deficient serum. She was diagnosed with acquired LCAT
deficiency. Her abnormalities of serum lipoproteins improved spontaneously during
three and a half years. Because they require different treatment strategies,
distinction between familial lecithin:cholesterol acyltransferase deficiency
(FLD) and acquired LCAT deficiency by gene sequencing is warranted, especially in
cases without corneal clouding.
PMID- 28508976
TI - Idiopathic collapsing focal segmental glomerulosclerosis in an 81-year-old
Japanese woman: a case report and review of the literature.
AB - Focal segmental glomerulosclerosis (FSGS) is classified into five variants, with
the collapsing variant being the most rare. Collapsing FSGS is characterized by a
black racial predominance and is often associated with human immunodeficiency
virus-associated nephropathy. However, the number of idiopathic cases is
increasing and the presentation of non-black patients becoming more routine. Our
analysis of 15 previous reports investigating FSGS variants shows that the
collapsing variant accounts for 10.6 % of FSGS cases and its average age of onset
is 32 years old. The current case is one of the oldest cases of idiopathic
collapsing FSGS identified, being an 81-year-old Japanese woman. She presented
with severe renal insufficiency (serum creatinine 7.9 mg/dL, albumin 1.5 g/dL)
and so underwent hemodialysis immediately. Urinalysis demonstrated 3+ proteinuria
and 3+ hematuria and the serological work up was all negative. Renal biopsy
showed wrinkling of capillary walls with collapse lumens in every glomerulus,
without endothelial tubuloreticular inclusions. Combined treatment with steroids,
cyclosporine and low-density lipoprotein apheresis increased urine output
slightly but she was unable to withdraw from hemodialysis and died 3 months
later. This variant is reported to have the highest rate of progression to end
stage renal disease, regardless of the therapeutic intervention. However, there
are also examples of cases with partial or complete remission in the literature.
Progressive cases, like the current case, seem to be difficult to induce
remission in, so it is important to diagnose idiopathic collapsing FSGS at an
early stage by performing a renal biopsy, even in elderly patients.
PMID- 28508977
TI - Thrombotic microangiopathy caused by interferon beta-1b for multiple sclerosis: a
case report.
AB - A 41-year-old man with a history of multiple sclerosis (MS) developed thrombotic
microangiopathy after taking interferon beta-1b for 10 years. Although the
relapse of his MS was well controlled under normal blood pressure, he had
persistent nausea, anorexia, gait disturbance and visual disorder 1 month before
admission. He showed lethargy and high blood pressure (180/102 mmHg). Laboratory
test results revealed anemia and thrombocytopenia, elevated LDH and renal
dysfunction. Urinary dipstick showed a 2+ result for proteinuria and 3+ for
hematuria. Schizocyte were present and haptoglobin decreased, and we diagnosed
him with possible thrombotic microangiopathy (TMA). Magnetic resonance image
indicated posterior reversible encephalopathy syndrome (PRES), which could be
accelerated by TMA. After discontinuing interferon beta-1b, high dose intravenous
methylpredonisolone, anti-hypertension therapy and plasma exchange was started.
Because a mild decrease in ADAMTS13 activity and absence of ADAMTS 13 inhibitor
could not cause thrombotic thrombocytopenic purpura, plasma exchange was stopped.
The patient's renal function recovered and PRES resolved, and he was discharged
with slightly decrease of visual acuity. We suggest that his TMA was likely
caused by interferon beta-1b, resulting in PRES in a patient with multiple
sclerosis. We report this rare case and also review the literature.
PMID- 28508978
TI - Acute tumoral calcinosis due to severe hyperphosphatemia in a maintenance
hemodialysis patient.
AB - We report the case of a maintenance hemodialysis patient with severe
hyperphosphatemia (26.6 mg/dL) who developed acute tumoral calcinosis. The
patient started receiving maintenance hemodialysis after being diagnosed with
type 2 diabetes mellitus. The patient's phosphate levels suddenly increased. He
had not taken the prescribed phosphate binders for the past 5 years. He noticed
swelling of the palmar aspects of his right thumb, which was diagnosed as tumoral
calcinosis. His serum phosphate level reached 26.6 mg/dL. He started taking
medication to lower his serum phosphate levels. The patient had a long history of
eating convenience foods. As food additives in convenience foods could be a major
source of phosphate, the patient corrected this habit by replacing convenience
foods with special foods for dialysis patients. His symptoms improved along with
the decrease in his serum phosphate levels. The main reason for the abrupt
decrease in phosphate levels could be the correction of his dietary habits.
Therefore, phosphate levels in processed foods should be carefully considered in
dialysis patients.
PMID- 28508979
TI - Urinothorax in a child secondary to obstructive renal stone in a solitary
functioning kidney: a case report.
AB - Urinothorax or presence of urine in pleural cavity is a highly unusual cause of
pleural effusion. It is most commonly secondary to genitourinary trauma and
obstructive uropathy. We here by present a case of urinothorax secondary to renal
stone disease in a 5-year-old child with a solitary functioning kidney.
PMID- 28508980
TI - An adult case of severe steroid-resistant Henoch-Schonlein purpura nephritis
treated with intravenous cyclophosphamide and tonsillectomy.
AB - A previously healthy 37-year-old Canadian man living in Japan visited a hospital
in Thailand while traveling because of edematous legs, purpura, arthralgia,
bloody stool, and fever after an insect bite. Henoch-Schonlein purpura (HSP) was
suspected. His creatinine level was 5.2 mg/dL. He was treated with oral
prednisolone (PSL) and oral cyclophosphamide (CPA); after treatment, his
creatinine level improved to 2.4 mg/dL. Upon returning to Japan, he was admitted
to the National Center for Global Health and Medicine Hospital in Tokyo. A kidney
biopsy was performed, and HSP nephritis (HSPN) was diagnosed. Renal dysfunction
and proteinuria persisted despite 4 administrations of steroid-pulse therapy and
3 sessions of plasma exchange. Finally, he was treated with intravenous
cyclophosphamide (IVCY). His creatinine level and proteinuria markedly improved.
His microscopic hematuria disappeared after he underwent tonsillectomy. There
have been only a few case reports describing patients with adult-onset HSPN
necessitating IVCY. We present here a rare case of steroid-resistant HSPN treated
with IVCY and tonsillectomy, with reference to some recent findings.
PMID- 28508981
TI - Partial remission by cyclosporine monotherapy in a patient with membranous
nephropathy superimposed diabetic nephropathy.
AB - It has been noted that cyclosporine A (CsA) is an effective drug for membranous
nephropathy (MN). Diabetes is a common disease that sometimes causes nephrotic
syndrome. We report the case of an 89-year-old woman with type 2 diabetes
mellitus who exhibited nephrotic syndrome. Examination of a renal biopsy
indicated MN and she was prescribed CsA as monotherapy. Her edema subsided and
she achieved partial remission. This is the first report of a patient in diabetic
condition with MN having achieved partial remission after CsA monotherapy without
steroid therapy. The use of steroid in patients with diabetes may worsen their
diabetic condition, especially if they are of very advanced age. CsA monotherapy
may be useful for diabetic patients with MN.
PMID- 28508982
TI - Renal hemorrhage caused by acquired inhibitors to coagulation factors VIII and V
in a hemodialysis patient.
AB - Acquired coagulation factor deficiency is a rare bleeding disorder caused by the
inhibitors to coagulation factors. We report a case of an elderly hemodialysis
patient who presented with the intermittent hematuria and anemia, associated with
the prolonged activated partial thromboplastin time and prothrombin time.
Laboratory examination revealed undetectable factor VIII activity, decreased
factor V activity, and the presence of inhibitors to these coagulation factors.
The patient was diagnosed to have inhibitors to coagulation factors VIII and V
simultaneously. In addition, hematuria was found to be caused by the right renal
hemorrhage. Renal extravasation was treated by transcatheter arterial
embolization. Oral prednisolone successfully eradicated the inhibitors. The
present case highlights the importance to consider acquired coagulation factor
inhibitors for bleeding symptoms, because they are sometimes life-threatening.
PMID- 28508983
TI - Effect of tolvaptan in a patient with autosomal dominant polycystic kidney
disease after living donor liver transplantation.
AB - Recently, a large randomized placebo-controlled trial indicated a beneficial
effect of tolvaptan on the progression of autosomal dominant polycystic kidney
disease (ADPKD) with near-normal kidney function. Meanwhile, the evidence of
tolvaptan's efficacy in ADPKD with severe renal insufficiency was limited and
higher frequency of liver enzyme elevations were observed in patients taking
tolvaptan. Liver transplantation (LT) is the only curative treatment for patients
with severe polycystic liver disease associated with ADPKD, but considering that
liver injuries should be avoided particularly in patients who underwent LT, we
must be careful to start tolvaptan in post-LT ADPKD patients. We describe the
case of a patient who had developed severe renal insufficiency after living donor
LT, for whom tolvaptan therapy showed marked reduction of total kidney volume and
maintenance of renal function without any serious adverse events. This is the
first report to show the beneficial effect and safety of tolvaptan, in a post-LT
ADPKD patient with severe renal insufficiency, and hopefully will help broaden
the spectrum of patients who will benefit from tolvaptan.
PMID- 28508985
TI - Light chain Fanconi syndrome in a patient with acute myeloid leukemia and
monoclonal gammopathy of undetermined significance.
AB - Proximal tubules are a target for paraproteinemic diseases. Cast nephropathy,
light chain deposition diseases, and amyloidosis are frequently encountered in
patients with multiple myeloma. Rarely, a subset of patients develop light chain
Fanconi syndrome (LCFS). LCFS has been reported with multiple myeloma, monoclonal
gammopathy of renal significance (MGRS), chronic lymphocytic leukemia,
Waldenstrom's macroglobulinemia and diffuse large B-cell lymphoma. No cases have
been described with other hematologic malignancies. We report the first case of
lambda LCFS in a patient with both acute myeloid leukemia (AML) and monoclonal
gammopathy of undetermined significance (MGUS).
PMID- 28508986
TI - List of referees.
PMID- 28508984
TI - Successful treatment of myeloma cast nephropathy using bortezomib-based
chemotherapy plus selective plasma exchange.
AB - Myeloma cast nephropathy is a major complication of multiple myeloma. Recent
evidence has demonstrated that the earlier induction of bortezomib-based
chemotherapy with plasma exchange (PE) provides better results for kidney
function and patient survival. Due to its non-selectivity, PE with albumin
replacement carries the risk of fibrinogen loss, leading to bleeding. We herein
report a case of successful treatment of myeloma cast nephropathy using
bortezomib-based chemotherapy and selective PE. A 61-year-old woman who had a 20
year history of type II diabetes mellitus was admitted to our hospital for the
evaluation of hypercalcemia, severe kidney dysfunction, and anemia. Subsequent
bone marrow evaluation and renal biopsy revealed that she had multiple myeloma
(IgG-kappa) and myeloma cast nephropathy. Ten days after admission, bortezomib
based chemotherapy with selective PE achieved rapid and thorough free light-chain
(FLC) reduction; within a month, her kidney function had been recovered
(creatinine level, 1.2 mg/dl). Her serum fibrinogen level was not reduced, and no
bleeding complication occurred. Five months later, autologous hematopoietic stem
cell transplantation was performed successfully, and the patient's kidney
function was stable (creatinine level, 1.1 mg/dl) thereafter. This case report
demonstrates the importance of early induction therapy with bortezomib-based
chemotherapy and PE in a patient with myeloma cast nephropathy, which is
especially applicable in patients aged <65 years. In addition, it shows that
selective PE is a safe and effective method of FLC removal.
PMID- 28508987
TI - Transmission of H6N2 wild bird-origin influenza A virus among multiple bird
species in a stacked-cage setting.
AB - Live bird markets are common in certain regions of the U.S. and in other regions
of the world. We experimentally tested the ability of a wild bird influenza A
virus to transmit from index animals to naive animals at varying animal densities
in stacked cages in a simulated live bird market. Two and six mallards, five and
twelve quail, and six and nine pheasants were used in the low-density and high
density stacks of cages, respectively. Transmission did not occur in the high
density stack of cages likely due to the short duration and relatively low levels
of shedding, a dominance of oral shedding, and the lack of transmission to other
mallards in the index cage. In the low-density stack of cages, transmission
occurred among all species tested, but not among all birds present. Oral and
cloacal shedding was detected in waterfowl but only oral shedding was identified
in the gallinaceous birds tested. Overall, transmission was patchy among the
stacked cages, thereby suggesting that chance was involved in the deposition of
shed virus in key locations (e.g., food or water bowls), which facilitated
transmission to some birds.
PMID- 28508988
TI - Guillain-Barre syndrome variant with facial diplegia and paresthesias after
reactivation of varicella zoster virus.
PMID- 28508989
TI - Evaluation of inner retinal layers with optic coherence tomography in vigabatrin
exposed patients.
AB - In order to reveal the underlying retinal pathology leading to dysfunction in
vigabatrin-exposed patients, we aimed to evaluate the inner retinal layers
encompassing ganglion cell complex (GCC) layer and inner plexiform layer with new
generation optic coherence tomography (OCT). Fourteen patients with epilepsy and
exposure to vigabatrin and 12 clinically normal individuals, constituting the
control group, were included. Retinal images were obtained using spectral-domain
OCT (Optovue RTVue Fourier domain). Nasal and superior quadrants of retinal nerve
fiber layer (RNFL) were found to be significantly lower in the patient group
compared to the controls (p < 0.01). No significant difference was shown in the
thickness of GCC layer (p > 0.05). Foveal thickness was significantly higher in
the patient group (p: 0.006), but no significant difference was found in
perifoveal and parafoveal regions between groups (p > 0.05). The thickness of
RNFL was found to be lower in vigabatrin-exposed patients without any reduction
in GCC layer in the macular region. However, foveal thickness was found to be
significantly higher compared to perifoveal and parafoveal macular regions in
vigabatrin-exposed patients. In conclusion, OCT revealed reduced thickness of
RNFL without any reduction in ganglion cell layer in our study. The objective
quantitative assessment of OCT is a practical noninvasive method and it can have
role in future monitoring of these patients.
PMID- 28508991
TI - Digital stethoscopes compared to standard auscultation for detecting abnormal
paediatric breath sounds.
AB - : Our study aimed to objectively describe the audiological characteristics of
wheeze and crackles in children by using digital stethoscope (DS) auscultation,
as well as assess concordance between standard auscultation and two different DS
devices in their ability to detect pathological breath sounds. Twenty children
were auscultated by a paediatric consultant doctor and digitally recorded using
the LittmanTM 3200 Digital Electronic Stethoscope and a ClinicloudTM DS with
smart device. Using spectrographic analysis, we found those with clinically
described wheeze had prominent periodic waveform segments spanning expiration for
a period of 0.03-1.2 s at frequencies of 100-1050 Hz, and occasionally spanning
shorter inspiratory segments; paediatric crackles were brief discontinuous sounds
with a distinguishing waveform. There was moderate concordance with respect to
wheeze detection between digital and standard binaural stethoscopes, and 100%
concordance for crackle detection. Importantly, DS devices were more sensitive
than clinician auscultation in detecting wheeze in our study. CONCLUSION:
Objective definition of audio characteristics of abnormal paediatric breath
sounds was achieved using DS technology. We demonstrated superiority of our DS
method compared to traditional auscultation for detection of wheeze. What is
Known: * The audiological characteristics of abnormal breath sounds have been
well-described in adult populations but not in children. * Inter-observer
agreement for detection of pathological breath sounds using standard auscultation
has been shown to be poor, but the clinical value of now easily available digital
stethoscopes has not been sufficiently examined. What is New: * Digital
stethoscopes can objectively define the nature of pathological breath sounds such
as wheeze and crackles in children. * Paediatric wheeze was better detected by
digital stethoscopes than by standard auscultation performed by an expert
paediatric clinician.
PMID- 28508992
TI - Palivizumab prophylaxis in infants with cystic fibrosis does not delay first
isolation of Pseudomonas aeruginosa or Staphylococcus aureus.
AB - : Respiratory syncytial virus (RSV) infections may worsen cystic fibrosis (CF)
lung disease and favor Pseudomonas aeruginosa (Pa) or Staphylococcus aureus (Sa)
acquisition, which is of particular importance in the youngest patients. We aimed
to determine the effectiveness of PVZ on microbiological outcomes in young
children with CF. We conducted a retrospective case-control study to compare
these outcomes in children who systematically received PVZ (PVZ+; n = 40) or not
(PVZ-; n = 140). One case was matched with at least three same-gender controls
born the same year and month. Median (range) age at first Pa isolation was not
statistically different between PVZ- (12.3 [3.8-32.6] months) and PVZ+ (10.4 [1.2
33.0] months; p = 0.953) patients. A similar trend was found for Sa (PVZ+: 6.4
[2.0-59.0] months; PVZ-: 3.8 [0.1-74.1] months; p = 0.191). The proportion of Pa
isolations by 3 years of age did not differ between groups (PVZ+ 40% vs. PVZ-
41.4%), but this proportion was higher for Sa in the PVZ+ group (97%) than in the
PVZ- group (85%; p = 0.001). Healthcare consumption and growth outcomes did not
significantly differ between groups. CONCLUSION: Systematic PVZ use did not delay
key pathogen acquisition in young children with CF. What is known: * Palivizumab
is the only available monoclonal antibody against respiratory syncytial virus
infection. * Whether or not it is useful in infants with cystic fibrosis remains
controversial. What is new: * Palivizumab does not delay key pathogens
(Pseudomonas aeruginosa, Staphylococcus aureus) first isolation in young children
with cystic fibrosis. * Palivizumab does not reduce healthcare consumption or
improve growth during the first 3 years of life of young children with cystic
fibrosis.
PMID- 28508990
TI - Adolescents with congenital heart disease: their opinions about the preparation
for transfer to adult care.
AB - : The aim of the study was to explore what adolescents with congenital heart
disease (CHD) view as important in the preparation for the transfer to adult
care. We performed interviews in four focus groups with adolescents (14-18 years
old) at four university hospitals in Sweden. Data was analysed using qualitative
content analysis. The analysis revealed one main category; Becoming a manager of
the condition and four subcategories; Sufficient knowledge about the health, Be a
participant in the care, Parental support, and Communicate with others about the
health. The adolescents' ages differentiated the discussion in the groups. The
older adolescents seemed to have more interest in transition planning,
information and transfer. The younger described more frustrations about
communication and handling the disease. CONCLUSION: To become a manager of the
CHD in daily life, the adolescents want disease specific knowledge, which should
be communicated in a developmentally appropriate way. Adolescents want to
participate and be involved in the transition process. They need support and
guidance in how to communicate their CHD. Parental support is fundamental but it
change over time. Moreover, peer-support is becoming more significant during the
transition process. What is Known: * Transition during adolescence and transfer
to adult care for adolescents with CHD is complex, and there is a shift in roles.
* Adolescents often have poor knowledge and understanding about their heart
condition and the consequences. What is New: * Adolescents call for disease
specific information regarding health issues of importance for them in daily
life. * Communicating the disease with other is a challenge- peer support from
other adolescents with CHD could be a facilitator.
PMID- 28508993
TI - 14,15-EET Suppresses Neuronal Apoptosis in Ischemia-Reperfusion Through the
Mitochondrial Pathway.
AB - Neuronal apoptosis mediated by the mitochondrial apoptosis pathway is an
important pathological process in cerebral ischemia-reperfusion injury. 14,15
EET, an intermediate metabolite of arachidonic acid, can promote cell survival
during ischemia/reperfusion. However, whether the mitochondrial apoptotic pathway
is involved this survival mechanism is not fully understood. In this study, we
observed that infarct size in ischemia-reperfusion injury was reduced in sEH gene
knockout mice. In addition, Caspase 3 activation, cytochrome C release and AIF
nuclear translocation were also inhibited. In this study, 14,15-EET pretreatment
reduced neuronal apoptosis in the oxygen-glucose deprivation and re-oxygenation
group in vitro. The mitochondrial apoptosis pathway was also inhibited, as
evidenced by AIF translocation from the mitochondria to nucleus and the reduction
in the expressions of cleaved-caspase 3 and cytochrome C in the cytoplasm. 14,15
EET could reduce neuronal apoptosis through upregulation of the ratio of Bcl-2
(anti-apoptotic protein) to Bax (apoptosis protein) and inhibition of Bax
aggregation onto mitochondria. PI3K/AKT pathway is also probably involved in the
reduction of neuronal apoptosis by EET. Our study suggests that 14,15-EET could
suppress neuronal apoptosis and reduce infarct volume through the mitochondrial
apoptotic pathway. Furthermore, the PI3K/AKT pathway also appears to be involved
in the neuroprotection against ischemia-reperfusion by 14,15-EET.
PMID- 28508994
TI - Disease-Modifying Effects of Neural Regeneration Peptide 2945 in the GAERS Model
of Absence Epilepsy.
AB - Epilepsy is a common neurological condition characterised by spontaneous
recurrent seizures. Current anti-epileptic drugs are only effective and tolerated
in ~70% of patients, leaving a substantial proportion of patients untreated. As
such, there is a pressing need to develop new therapies. We assessed the anti
seizure activity of Neural Regeneration Peptide 2945 (NRP 2945) in the GAERS
model of absence epilepsy. Drug effects on seizures were assessed using two study
designs. Male adult GAERS were implanted with EEG electrodes to measure seizure
frequency. The first study compared the effects of acute sc injection of vehicle,
NRP 10 ug/kg, NRP 20 ug/kg, and controlled against the active comparator
Valproaic acid (200 mg/kg). In the second study, animals received one of four
treatments for 4 weeks: vehicle, NRP 60 ug/kg/day, NRP 120 ug/kg/day (delivered
by continuous infusion) or NRP 20 ug/kg sc injected every second day (e.s.d). In
the acute study, we found significant (p < 0.01) anti-seizure effects in animals
treated with NRP2945 (20 ug/kg) and VPA, with NRP2945 slightly more efficacious,
despite the 70,000 times lower molar dosage. In the chronic study, animals
receiving 120 ug/kg/day and NRP 20 ug/kg e.s.d had significantly fewer seizures
(p < 0.001), compared with vehicle. These effects were sustained for at least 10
days after drug treatment had ceased, indicative of disease-modifying activity.
We demonstrate sustained anti-seizure effects of NRP2945, a potent small molecule
peptide which enters the brain and is devoid of adverse effects. Early stage
first-in-man trials have been initiated for subcutaneously delivered NRP2945
which is a promising step to providing therapeutic benefits for refractory
epilepsy patients.
PMID- 28508996
TI - Hyalinizing Clear Cell Carcinoma of the Bronchus.
AB - Hyalinizing clear cell carcinoma (HCCC) is an uncommon low-grade minor salivary
gland neoplasm that usually arises in the head and neck region. We report a 55
year-old man who presented with a 2.5 cm lung mass that was partially obstructing
the right bronchus intermedius. The tumor consisted of cords and nests of clear
and eosinophilic cells in a hyalinized stromal background. The neoplastic cells
expressed cytokeratin (CK) 7, CK 5/6, high-molecular weight cytokeratin (34BE12),
p63 and p40, while TTF-1, napsin A, CK20, S100, smooth muscle actin,
synaptophysin and chromogranin were negative. Mucicarmine stain also was negative
in the lesional cells. Fluorescence in situ hybridization using break apart
probes revealed rearrangement of the Ewing Sarcoma Breakpoint Region 1 gene
locus. The morphologic, immunophenotypic and cytogenetic findings confirmed the
diagnosis of HCCC, most likely of bronchial submucosal gland origin. To our
knowledge, only two other reports of primary pulmonary HCCC are available in
English literature.
PMID- 28508998
TI - ?
PMID- 28508999
TI - ?
PMID- 28508997
TI - Fibromyxoma of the Jaw: Case Report and Review of the Literature.
AB - We report a case of fibromyxoma of the mandible, a rare benign odontogenic tumor.
Our patient presented in the first trimester of pregnancy with a large mass in
the right body of the mandible exhibiting displacement of teeth and destruction
of an extensive area of the mandibular bone. The mass was biopsied and diagnosed
as a fibromyxoma. The large size of the tumor dictated a wide mandibular
resection. We will review the clinical, radiographic, and histologic features of
fibromyxoma and discuss its differential diagnoses. In addition, we will provide
an overview of patient management. Fibromxyoma is a benign gnathic tumor that can
be locally aggressive. To ensure appropriate treatment, it is important to
distinguish this neoplasm from other mimickers in which myxoid, spindle
mesenchymal cell proliferation is prominent.
PMID- 28509000
TI - ?
PMID- 28509001
TI - ?
PMID- 28509003
TI - ?
PMID- 28509004
TI - ?
PMID- 28509002
TI - ?
PMID- 28508995
TI - L-Carnitine and Acetyl-L-carnitine Roles and Neuroprotection in Developing Brain.
AB - L-Carnitine functions to transport long chain fatty acyl-CoAs into the
mitochondria for degradation by beta-oxidation. Treatment with L-carnitine can
ameliorate metabolic imbalances in many inborn errors of metabolism. In recent
years there has been considerable interest in the therapeutic potential of L
carnitine and its acetylated derivative acetyl-L-carnitine (ALCAR) for
neuroprotection in a number of disorders including hypoxia-ischemia, traumatic
brain injury, Alzheimer's disease and in conditions leading to central or
peripheral nervous system injury. There is compelling evidence from preclinical
studies that L-carnitine and ALCAR can improve energy status, decrease oxidative
stress and prevent subsequent cell death in models of adult, neonatal and
pediatric brain injury. ALCAR can provide an acetyl moiety that can be oxidized
for energy, used as a precursor for acetylcholine, or incorporated into
glutamate, glutamine and GABA, or into lipids for myelination and cell growth.
Administration of ALCAR after brain injury in rat pups improved long-term
functional outcomes, including memory. Additional studies are needed to better
explore the potential of L-carnitine and ALCAR for protection of developing brain
as there is an urgent need for therapies that can improve outcome after neonatal
and pediatric brain injury.
PMID- 28509006
TI - ?
PMID- 28509005
TI - ?
PMID- 28509007
TI - ?
PMID- 28509008
TI - ?
PMID- 28509009
TI - ?
PMID- 28509010
TI - ?
PMID- 28509012
TI - [Standardized blood pressure measurement in clinical practice].
PMID- 28509011
TI - ?
PMID- 28509013
TI - [Mental disorders and problems in afghan refugees: The clinical perspective].
PMID- 28509014
TI - ?
PMID- 28509015
TI - [Injuries due to marine animals].
PMID- 28509017
TI - [Diving accidents].
PMID- 28509016
TI - [Diving accidents].
PMID- 28509018
TI - ?
PMID- 28509019
TI - ?
PMID- 28509020
TI - ?
PMID- 28509021
TI - ?
PMID- 28509022
TI - ?
PMID- 28509023
TI - ?
PMID- 28509024
TI - ?
PMID- 28509026
TI - ?
PMID- 28509025
TI - ?
PMID- 28509028
TI - ?
PMID- 28509027
TI - ?
PMID- 28509029
TI - ?
PMID- 28509030
TI - ?
PMID- 28509032
TI - ?
PMID- 28509031
TI - ?
PMID- 28509033
TI - ?
PMID- 28509034
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PMID- 28509036
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PMID- 28509035
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PMID- 28509037
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PMID- 28509038
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PMID- 28509039
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PMID- 28509040
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PMID- 28509041
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PMID- 28509042
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PMID- 28509043
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PMID- 28509045
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PMID- 28509046
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PMID- 28509044
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PMID- 28509048
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PMID- 28509047
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PMID- 28509049
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PMID- 28509050
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PMID- 28509051
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PMID- 28509052
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PMID- 28509054
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PMID- 28509055
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PMID- 28509056
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PMID- 28509057
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PMID- 28509058
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PMID- 28509059
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PMID- 28509060
TI - [Management of benign prostatic hyperplasia (BPH)].
PMID- 28509061
TI - Cardiomyopathy mimicking left ventricular noncompaction in a patient with lupus
nephritis.
AB - A 37-year-old female patient was admitted with exertional dyspnea. Her serum
creatinine was 2.4 mg/dL and anti-nuclear antibody was positive in a titer of
1/320. Renal biopsy revealed diffuse proliferative lupus nephritis.
Echocardiography and cardiac magnetic resonance (MR) imaging showed increased
apical trabeculations compatible with left ventricular noncompaction (LVNC),
which is a rare genetic cardiomyopathy. The patient expressed a marked
improvement in exertional dyspnea after the immune-suppressive treatment for
systemic lupus erythematosus (SLE). Control echocardiography revealed a
significant increase of ejection fraction. SLE may cause a kind of cardiomyopathy
with high resemblance to LVNC. Discrimination of these two similar clinical
entities is important because SLE-induced cardiomyopathy is potentially
reversible after the immune-suppressive treatment for SLE.
PMID- 28509062
TI - True identity of endocapillary proliferation: a case of intravascular large B
cell lymphoma diagnosed with immunohistochemical study of kidney biopsy and
literature review.
AB - A 78-year-old Japanese female presented with low-grade fever, malaise, and
appetite loss lasting for 1 month. Upper and lower gastrointestinal endoscopy and
contrast-enhanced whole-body computed tomography (CT) revealed no abnormal
findings at a referring hospital. She was referred to our hospital because of
bilateral leg edema and 2.5 g/day proteinuria. Serum creatinine was 0.73 mg/dl
and the kidneys were not enlarged. Kidney biopsy showed marked endocapillary
proliferation with mesangiolysis. Soon after the kidney biopsy, her symptoms
improved spontaneously, along with decreases in lactate dehydrogenase (LDH) from
503 to 197 IU/l, C-reactive protein (CRP) from 4.47 to 0.66 mg/dl, and soluble
interleukin-2 receptor (sIL-2R) from 1789 to 1001 U/ml. Thus, she was followed
carefully as an outpatient. One month later, however, she presented with
dysarthria and right-sided hemiparesis, and diffusion-weighted brain magnetic
resonance imaging (MRI) showed multiple high-intensity areas. She also had
respiratory failure, and lung perfusion scintigraphy showed multiple low blood
stream areas. Suspecting some endovascular abnormality, we performed
immunohistochemical staining of the kidney biopsy specimen taken previously to
find that endocapillary infiltrating cells were CD20-positive B lymphocytes. The
infiltrating cells were confined to the endocapillary compartment in glomeruli
and peritubular capillaries. Both clinical and pathological findings led us to
diagnose intravascular large B cell lymphoma (IVLBCL). Two bone marrow biopsies
and random skin biopsies were performed, but no abnormality was found. The
present case demonstrates that clinical course and renal biopsy findings of
intravascular large B cell lymphoma may mimic other renal conditions and that the
identification of cell types with immunohistochemical staining may help establish
an accurate diagnosis.
PMID- 28509063
TI - Successful treatment with tolvaptan to control blood volume and hyponatremia in a
chronic kidney disease patient.
AB - We report a case of successful treatment with tolvaptan (15 mg/day) in a 73-year
old female patient with chronic kidney disease (CKD) stage 5 due to diabetic
nephropathy and renal sclerosis for volume control and loop diuretic-induced
hyponatremia. Her creatinine clearance has remained at 7-10 ml/min for the last 6
months. She was treated by dietary and drug therapy, namely, antihypertensives
(nifedipine: 40 mg/day, olmesartan: 20 mg/day) and loop diuretics (azosemide: 40
120 mg/day), for CKD and concomitant diseases of hypertension and diabetic
mellitus. She developed loop diuretic-induced hyponatremia (120 mmol/l) by
increased sodium excretion, but the diuretic was required for the control of
volume overload. Hence, azosemide was suspended and tolvaptan (15 mg/day) was
administered. After tolvaptan treatment, the plasma sodium level gradually
increased to a normal level (135-140 mmol/l) and volume overload was improved.
Urine volume was maintained at about 1000 ml/day with low sodium excretion (<40
mmol/day) and increased free water clearance. These results suggest that
tolvaptan may be effective for volume control and diuretic-induced hyponatremia
in CKD patients.
PMID- 28509064
TI - Pasteurella multocida peritonitis associated with a cat in a peritoneal dialysis
patient using an automated cycler device.
AB - Pasteurella multocida (P. multocida) is an aerobic Gram-negative coccobacillus,
which is found as part of the natural oral flora of many animals, including most
healthy cats and dogs. However, it can cause a variety of infections in humans,
usually as a result of the patient being bitten or scratched by a cat or dog.
There have been 22 reported cases of P. multocida peritonitis in patients
undergoing peritoneal dialysis (PD). Of these, 66.7 % occurred within 12 months
of the initiation of PD. Only two cases (11.1 %) developed more than 60 months
after the commencement of PD. We report a case of P. multocida peritonitis
involving a 45-year-old patient who had been undergoing continuous ambulatory
peritoneal dialysis (CAPD) for 84 months without a previous history of
peritonitis, who developed P. multocida peritonitis associated with a domestic
cat on the very night on which he began using an automated cycler device to
switch from CAPD to continuous cyclic peritoneal dialysis (CCPD). Patients
maintained on PD who keep pets such as cats or dogs at home should be educated
about the risk of developing peritonitis related to their domestic pets, and this
warning should be repeated when such patients switch from CAPD to CCPD.
Physicians should consider using empiric therapy to prevent P. multocida in pet
owning PD patients who present with a history of PD fluid leakage and
peritonitis, especially in patients who use cycler devices.
PMID- 28509065
TI - A case report of mediastinal seminoma arising after renal transplantation.
AB - Recipients of organ transplantation on immunosuppressive medications are at
increased risk for developing de novo malignancies, including skin cancer,
Kaposi's sarcoma, in situ carcinomas of the uterine cervix, anogenital cancers,
renal cell carcinoma, and post-transplant lymphoproliferative disorders (PTLD).
However, there are few case reports of germ cell tumors after organ
transplantation. There are some case reports of testicular seminoma, but not
mediastinal seminoma. This case report is the first description of a mediastinal
seminoma that developed de novo 28 months after renal transplantation and that
was initially diagnosed as PTLD. To improve outcomes of organ transplant
recipients, it is important to report rare cases of malignancies arising while on
immunosuppressive medications. When we detect mediastinal tumor arising after
organ transplantation while on immunosuppressive therapy, diseases other than
PTLD should be considered in the differential diagnosis.
PMID- 28509066
TI - Cyclophosphamide induced early-onset interstitial lung disease.
PMID- 28509067
TI - Intracranial calcification in a uremic infant with Wilms' tumor in a solitary
kidney.
AB - Wilms' tumor (WT), also called nephroblastoma, is an embryonic neoplasm of the
developing kidney. A previously healthy Japanese female infant had WT in a single
kidney without associated congenital malformations. Preoperative chemotherapy was
started for the preservation of renal tissue and function. Tumor lysis syndrome,
disseminated intravascular coagulopathy, and acute renal failure were
accompanying. The infant needed surgical intervention and permanent replacement
therapy. At the start of emergency hemodialysis, the infant had posterior
reversible leukoencephalopathy syndrome because of severe hypertension. During
ongoing peritoneal dialysis, the infant suffered from anemia, dietary and fluid
restriction, and restriction of time and mobility. Despite alfacalcidol and
calcium supplementation, the infant had secondary hyperparathyroidism and
remarkably short stature. After waiting for the completion of chemotherapy, renal
transplantation from the mother was completed. Successful kidney transplantation
promptly corrected preexisting metabolic abnormalities causing secondary
hyperparathyroidism. Subsequently, the infant often complained of headache.
Computed tomographic scanning revealed calcification in the cerebellum.
Refractory secondary hyperparathyroidism was inferred as the cause. A well
functioning graft provided the infant with a greater sense of well-being and
enabled her to enjoy a lifestyle free of dialysis, although the infant must
continue taking transplant medications and has retained unresolved issues of
short stature and ectopic intracranial calcification.
PMID- 28509068
TI - The combined use of edaravone, diuretics, and nonsteroidal anti-inflammatory
drugs caused acute kidney injury in an elderly patient with chronic kidney
disease.
AB - The purpose of this study was to draw attention to the fact that the combined use
of edaravone, diuretics, and nonsteroidal anti-inflammatory drugs (NSAIDs) may
lead to acute kidney injury. This study was a case report of acute kidney injury
resulting from the combined use of the aforementioned types of drugs. A 77-year
old male patient with chronic kidney disease (third stage) who was treated with a
combination of edaravone, diuretics, and NSAIDs showed significantly increased
blood urea nitrogen and creatinine. Interestingly, the blood urea nitrogen and
creatinine levels returned to pretreatment levels after the medications were
stopped. The patient's score on the Naranjo Adverse Drug Reaction Probability
Scale was a nine, and the score on the Drug Interaction Probability Scale was a
five. For elderly patients with chronic kidney disease, the combined use of
edaravone, diuretics, and NSAIDs should be avoided.
PMID- 28509069
TI - A case of the "cellular variant" of focal segmental glomerulosclerosis with acute
renal failure that remitted completely with oral steroid administration.
AB - A 73-year-old man with systemic edema and oliguria, which appeared within several
days, was referred to our hospital. Urinalysis showed massive proteinuria, and
the blood examination results indicated nephrotic syndrome. Renal biopsy revealed
the existence of focal segmental glomerulosclerosis (FSGS), and further
investigation indicated that the microscopic features were consistent with the
"cellular variant (CELL)" according to the Columbia Classification. After biopsy,
40 mg per day of oral prednisolone was administered daily. With steroid therapy,
the abnormal values of the blood examination and urinalysis gradually reached
normal, and complete remission was achieved on day 43 after initiating steroid
administration. Microscopic investigation by follow-up renal re-biopsy revealed
several sclerosing glomeruli; however, other intact glomeruli had no endothelial
proliferation, which is a hallmark of CELL. The patient was discharged after
biopsy and observed as an outpatient, with maintenance of clinical remission.
PMID- 28509071
TI - Fever associated with severe dialysis-related amyloidosis.
AB - Dialysis-related amyloidosis (DRA) is one of the most important complications in
patients on long-term hemodialysis (HD). DRA often affects the osteoarticular
system; however, little is known about the role of beta2-microglobulin in the
induction of fever in HD patients. We report a 64-year-old woman on long-term (24
years) HD who developed polyarthralgia and intermittent fever. Infectious
diseases, connective tissue diseases, and malignant neoplasm were ruled out.
Computed tomography and magnetic resonance imaging showed swelling of the soft
tissues around bilateral shoulder and hip joints, suggestive of amyloid deposits.
Gallium scintigraphy showed abnormal uptake in the vicinity of several large
joints. It was presumed that the fever was related to the amyloid joint deposits,
and the patient was treated with prednisolone and beta2-microglobulin adsorption
therapy. The treatment resulted in the resolution of fever, relief of arthralgia,
and normalization of several inflammatory cytokines and C-reactive protein. The
findings suggest that massive DRA could cause systemic inflammatory response in
patients on long-term HD.
PMID- 28509072
TI - Urgent hemodialysis induced an acute gout attack in a patient with multiple
tophi: report of a rare case.
PMID- 28509070
TI - A case of (double) ANCA-negative granulomatosis with polyangiitis (Wegener's).
AB - A 60-year-old man had experienced cough, bloody sputum, and a 38 degrees C fever
for 1.5 months. He visited an outpatient clinic and received antibiotics and
nonsteroidal anti-inflammatory drugs. However, because the symptoms continued, he
visited our hospital. The past medical history included chronic sinusitis,
hypertension, and diabetes mellitus. A chest x-ray film and computed tomography
showed multiple pulmonary nodules with cavities. Macrohematuria had developed 3
days before admission, and renal function had deteriorated (creatinine, 2.45
mg/dL) in 2 weeks. He was admitted to our hospital because of rapidly progressive
glomerulonephritis (RPGN) and multiple pulmonary nodules. On admission, the
clinical diagnosis was suspected to be granulomatosis with polyangiitis
(Wegener's) (GPA), although tests for proteinase-3 anti-neutrophil cytoplasmic
antibody (PR3-ANCA) were negative. Antibiotics were administered for 5 days.
After renal biopsy, methylprednisolone pulse therapy and cyclophosphamide pulse
therapy were performed. The pathological diagnosis on the basis of the renal
biopsy was glomerular and interstitial hemorrhage, possibly associated with
vasculitis. After the treatment, the pulmonary symptoms, multiple pulmonary
nodules, and severe inflammatory reactions in the peripheral blood were resolved.
However, renal dysfunction progressed to end-stage renal disease 1 month after
renal biopsy. Hemodialysis was started, and the steroid therapy was continued.
During hemodialysis, a second renal biopsy was performed and led to a diagnosis
of pauci-immune focal segmental crescentic glomerulonephritis. Renal function
gradually recovered, and hemodialysis was discontinued. This case was (double)
ANCA-negative GPA which presented prominent glomerular and interstitial
hemorrhage, may be associated with small vessel vasculitis, but without active
necrotizing and crescentic glomerular lesions, in the rapidly progressive
glomerulonephritis.
PMID- 28509073
TI - Systemic and rapidly progressive light-chain deposition disease initially
presenting as tubulointerstitial nephritis.
AB - A 42-year-old woman was admitted to a hospital after first-time detection of
proteinuria and hematuria during a routine medical check-up. Because her serum
creatinine level had rapidly increased from 0.9 to 3.2 mg/dl since measurement 3
months earlier, she was referred to our hospital. Renal biopsy revealed extensive
tubular atrophy and interstitial fibrosis with mild leukocyte infiltration.
Glomeruli showed minimal changes, and no immunoglobulin or complement deposition
was observed by immunofluorescence. Oral prednisolone was commenced under the
diagnosis of chronic tubulointerstitial nephritis, and she discharged once.
However, its effects were transient; her renal function deteriorated rapidly and
hemodialysis was initiated 5 months after her initial check-up. On readmission,
urinary Bence-Jones protein kappa-type was detected, and examination of bone
marrow led to a diagnosis of Bence-Jones kappa-type multiple myeloma. Light-chain
staining using a renal biopsy specimen obtained 2 months earlier showed kappa
light-chain deposition on tubular basement membranes but not glomeruli. Despite
undergoing chemotherapy with vincristine, doxirubicin, and dexamethasone, the
patient died suddenly from a cardiac arrhythmia. Autopsy showed kappa-light-chain
deposition in the heart, thyroid, liver, lungs, spleen, and ovaries. Congo red
staining yielded negative results. Typical light-chain deposition disease (LCDD)
characterized by nodular glomerulosclerosis was observed in the kidneys. This
case demonstrates that tubulointerstitial nephritis can be an early pathological
variant of LCDD, which may be followed by accelerated and massive light-chain
deposition in glomeruli.
PMID- 28509074
TI - Osteomalacia secondary to renal tubular acidosis due to Sjogren's syndrome: a
case report and review of the literature.
AB - A 43-year-old woman was admitted to our hospital because of generalized bone
pain. Arterial blood gas showed pH 7.266, HCO3- 13.5 mEq/l, and anion gap (AG)
12. Since her urine pH was 7.0 despite metabolic acidosis with normal AG, we
diagnosed distal renal tubular acidosis (RTA). Serum phosphate was 2.5 mg/dl, the
level of beta2 microglobulin was 41100 MUg/l, and aminoaciduria was present.
These results indicated proximal tubular dysfunction. The radiograph showed
pseudofracture in the pubic bone, indicating osteomalacia. Bone scintigram showed
abnormal accumulations of 99mTc-HMDP in multiple joints. Then, her generalized
bone pain was considered to be a symptom of osteomalacia. Despite the absence of
overt Sicca syndrome, the evaluation of Sjogren's syndrome (SjS) as a cause of
distal RTA was performed. Antibodies to the SS-A level was 127U/ml. Tear break-up
time was 3 s bilaterally and salivary gland scintigraphy showed low uptake of
99mTc in the submandibular glands and the parotids. Thus, we diagnosed SjS
finally. Gallium scintigraphy showed mild abnormal uptake in bilateral kidneys,
suggesting acute tubulointerstitial nephritis. After treatment with prednisolone,
alfacalcidol, and sodium bicarbonate, bone pain was remarkably relieved.
Additionally, aminoaciduria disappeared and the level of beta2 microglobulin
decreased. We speculated that the coincidence of proximal tubular dysfunction and
distal RTA cause a severe manifestation of osteomalacia.
PMID- 28509075
TI - List of referees.
PMID- 28509076
TI - Efficacy of antihistamines on mortality in patients receiving maintenance
hemodialysis: an observational study using propensity score matching.
AB - Antihistamines are widely used to treat pruritus in patients receiving
hemodialysis. In a previous cross-sectional study, we reported an association
between antihistamine use and the absence of eccentric cardiac hypertrophy in
patients receiving hemodialysis. Therefore, in this study, we sought to evaluate
the efficacy of antihistamines on all-cause and cardiovascular mortality in
patients receiving hemodialysis according to our outpatient dialysis database. We
used a propensity score matching method. Among the 389 patients receiving
hemodialysis according to our database, we extracted those taking antihistamines
and matched them with patients not taking antihistamines using propensity scores
based on 38 variables. All-cause mortality and cardiovascular mortality were
estimated by the Kaplan-Meier method, and a log-rank test was used to examine the
differences between the survival curves. We included 154 patients, or 77 matched
pairs, from the entire cohort (c-statistic = 0.78, p < 0.0001). There were no
differences in any background factor between the antihistamine and non
antihistamine group. During the mean observational period of 5.4 years, 50
patients died, and the all-cause mortality rate was 27.3% (21 patients) in the
antihistamine group and 37.3% (29 patients) in the non-antihistamine group (p =
0.0314). The cardiovascular mortality rate was 16.9% (13 patients) in the
antihistamine group and 25.9% (20 patients) in the non-antihistamine group (p =
0.0417). The results of this study suggest that all-cause and cardiovascular
mortality improved with antihistamine use in patients receiving hemodialysis.
However, the clinical efficacy of antihistamines needs to be confirmed in a
prospective randomized study in the future.
PMID- 28509077
TI - Relationships between cognitive impairment on ADAS-cog and regional cerebral
blood flow using SPECT in late-onset Alzheimer's disease.
AB - The aim of this study was to examine brain hypoperfusion and its relationship
with cognitive dysfunction in late-onset Alzheimer's disease (AD). Forty patients
with late-onset AD and not receiving acetylcholinesterase inhibitors were
recruited from outpatient clinics. We examined cognitive function using the
Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and brain
perfusion using single-photon emission computed tomography, and analyzed
classified gyrus level segments with three-dimensional stereotactic surface
projection and the stereotactic extraction estimation method level 3. ADAS-cog
subscales were grouped into three domains: language, memory, and praxis. Patients
with late-onset AD showed an apparent reduction in regional cerebral blood flow
(rCBF) with a z score >1.5 in the frontal, temporal, and limbic lobes, with
lesser reduction in the parietal and occipital lobes. Although hypoperfusion in
the orbital, rectal, and subcallosal gyri of the frontal lobe was prominent, rCBF
in the inferior frontal gyrus of the frontal lobe was significantly correlated
with ADAS-cog total and language and praxis subscale scores. The parahippocampal
gyrus of the limbic lobe was also significantly correlated with the ADAS-cog
total, language, and praxis subscale scores. Additionally, the cingulate of the
limbic lobe was significantly related with ADAS-cog memory. In spite of lesser
hypoperfusion, the posterior cingulate gyrus of the limbic lobe was significantly
related with ADAS-cog total, language, and memory subscale scores. Further, each
subdivision of ADAS-cog was found to be related with various brain regions.
PMID- 28509080
TI - Evaluation of dose enhancement in presence of gold nanoparticles in eye
brachytherapy by 103Pd source.
AB - In recent years, the use of gold nanoparticles in radiation therapy has been
introduced as a new approach in radiotherapy. The aim of this study is to
investigate the effect of gold nanoparticles (GNPs) in plaque brachytherapy for
choroidal melanoma using Monte Carlo (MC) simulation. MCNPX code was used for
simulation of human eye, 103Pd (model 200) brachytherapy source and the 20 mm
COMS eye plaque that was loaded with 24 103Pd seeds and standardized by
Collaborative Ocular Melanoma Study (COMS). The tumour was defined from the inner
surface of choroid with 0.55 cm height and latticed with gold nanospheres and it
was filled with different concentrations of 5, 10 and 15 mg/g GNPs, separately.
Dose rate and dose enhancement factor in tumour and normal tissues of the eye
(without gold) was examined for this case and compared with gold-water mixture of
the same concentrations distributed in the tumour. The results show that with
increasing the concentration of GNPs, the dose in the tumour increases and the
dose to the normal tissues decreases. Furthermore, the time that is required to
deliver the prescribed dose to the tumour decreases. In the gold nanosphere case
for 5, 10 and 15 mg/g concentrations, the DEF in the apex of the tumour are 1.28,
1.46, 1.44 and at the distance of 6.5 mm in the normal tissue (outside the
tumour) this factor would be 0.82, 0.73 and 0.68. The comparison between two
cases of gold nanospheres and gold-water mixture shows that when the gold
concentrations are defined as mixed with water, the dose enhancement in the first
depths are higher than when the gold-nanoparticles are distributed inside the
tumour. Furthermore due to more reduced particle flux for water-mixture case, by
an increase in the depth the dose enhancement in gold-nanosphere increases
compared with gold-water mixture case.
PMID- 28509079
TI - "Pseudo-progression" in advanced thyroid cancer in response to kinase inhibitor
therapy.
PMID- 28509078
TI - The effects of vitamin D supplementation on proatherogenic inflammatory markers
and carotid intima media thickness in subjects with metabolic syndrome: a
randomized double-blind placebo-controlled clinical trial.
AB - PURPOSE: Metabolic syndrome may predispose to cardiovascular diseases. Since, in
recent studies, vitamin D is advocated for cardioprotective roles, this study was
designed to investigate the effects of vitamin D supplementation on
proatherogenic inflammatory markers and common carotid intima media thickness in
subjects with metabolic syndrome. METHODS: This randomized double blind clinical
trial was conducted in Tabriz, Iran. Eligible subjects (n = 80) with metabolic
syndrome were recruited thorough advertisement and randomized to receive either
vitamin D (50,000 IU/week) or matching placebo for 16 weeks. Interlukin-6, high
sensitivity C-reactive protein, vascular cell adhesion molecule-1, E-selectin,
and common carotid intima media thickness were measured at the beginning and end
of the study. The study was registered at http://www.irct.ir (code:
IRCT201409033140N14). RESULTS: Sixteen weeks supplementation with vitamin D
increased median of serum 25-hydroxy vitamin D [25(OH)D] and mean calcium levels
(p < 0.001) in the intervention group. There was also a significant difference in
parathyroid hormone level at the end of the study (p < 0.001). Vitamin D
treatment reduced IL-6 level after 16 weeks (p = 0.027). Compared to baseline,
vascular cell adhesion molecule-1 and E-selectin levels decreased significantly
in vitamin D treated subjects; however, there were no significant differences
between two groups. No effect of vitamin D supplementation was observed in either
common carotid intima media thickness or high sensitivity C-reactive protein
concentrations at the end of the study (p > 0.05). CONCLUSIONS: Vitamin D
supplementation improved some proatherogenic inflammatory markers in subjects
with metabolic syndrome. No changes of high sensitivity C-reactive protein and
carotid intima media thickness were shown after 16 weeks.
PMID- 28509084
TI - Whole-Exome Sequencing Identifies a Novel Homozygous Frameshift Mutation in the
MTMR2 Gene as a Causative Mutation in a Patient with Charcot-Marie-Tooth Disease
Type 4B1.
AB - Charcot-Marie-Tooth (CMT) disease refers to a heterogeneous group of axonal and
demyelinating polyneuropathies, characterized by chronic motor and sensory
dysfunction. CMT is the most common genetic cause of neuropathy. The present
study aimed to identify the gene mutation responsible for CMT in Ashkenazi Jew
(AJ) patient. Genomic DNA was extracted from whole blood leukocytes of affected
family and normal subject. Whole-exome sequencing was performed using the
Illumina HiSeq2500. The DNA region containing the identified mutation was
amplified by PCR and sequenced using dye-terminator chemistry and the forward
primer. Physical examination of the patient revealed weakness and atrophy of the
lower extremity muscles and Pes cavus foot deformity. Whole-exome sequencing
indicated that the patient is homozygous for a novel frameshift mutation
(c.1877_1878insAGAG, p.Arg630fs) in the myotubularin-related protein-2 gene
(MTMR2), which resulted in an erroneous C-terminal sequence and extension by 15
amino acids. Patients' parents are healthy, and DNA sequencing analysis indicated
that both are heterozygotes to the described mutation. The clinical feature of
the patient may indicate a complete co-segregation of the p.Arg630fs mutation in
MTMR2 gene with the CMT type 4B1 phenotype. Further studies are needed in order
to estimate the prevalence of this mutation among AJ.
PMID- 28509081
TI - Interleukin-6-Mediated Induced Pluripotent Stem Cell (iPSC)-Derived Neural
Differentiation.
AB - In an aging society with an increasing threat to higher brain cognitive functions
due to dementia, it becomes imperative to identify new molecular remedies for
supporting adult neurogenesis. Interleukin-6 (IL-6) is a promising cytokine that
can support neurogenesis under conditions of neurodegeneration, and neuron
replacement is eventually possible due to its agonistic acting soluble receptor
sIL-6R. Here, we report that activation of the IL-6-signal transducer and
activator of transcription 3 (STAT3) axis is neurogenic and has potential
therapeutic applications for the treatment of neurodegenerative diseases such as
Parkinson's disease (PD).
PMID- 28509082
TI - Atg7-Mediated Autophagy Is Involved in the Neural Crest Cell Generation in Chick
Embryo.
AB - Autophagy plays a very important role in numerous physiological and pathological
events. However, it still remains unclear whether Atg7-induced autophagy is
involved in the regulation of neural crest cell production. In this study, we
found the co-location of Atg7 and Pax7+ neural crest cells in early chick embryo
development. Upregulation of Atg7 with unilateral transfection of full-length
Atg7 increased Pax7+ and HNK-1+ cephalic and trunk neural crest cell numbers
compared to either Control-GFP transfection or opposite neural tubes, suggesting
that Atg7 over-expression in neural tubes could enhance the production of neural
crest cells. BMP4 in situ hybridization and p-Smad1/5/8 immunofluorescent
staining demonstrated that upregulation of Atg7 in neural tubes suppressed the
BMP4/Smad signaling, which is considered to promote the delamination of neural
crest cells. Interestingly, upregulation of Atg7 in neural tubes could
significantly accelerate cell progression into the S phase, implying that Atg7
modulates cell cycle progression. However, beta-catenin expression was not
significantly altered. Finally, we demonstrated that upregulation of the Atg7
gene could activate autophagy as did Atg8. We have also observed that similar
phenotypes, such as more HNK-1+ neural crest cells in the unilateral Atg8
transfection side of neural tubes, and the transfection with full-length Atg8-GFP
certainly promote the numbers of BrdU+ neural crest cells in comparison to the
GFP control. Taken together, we reveal that Atg7-induced autophagy is involved in
regulating the production of neural crest cells in early chick embryos through
the modification of the cell cycle.
PMID- 28509083
TI - Detection of CSF 14-3-3 Protein in Sporadic Creutzfeldt-Jakob Disease Patients
Using a New Automated Capillary Western Assay.
AB - Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal rapidly progressive
dementia. The detection of 14-3-3 protein in cerebrospinal fluid (CSF) is
included in the WHO diagnostic criteria for the pre-mortem diagnosis of CJD. The
aim of this study is to assess CSF 14-3-3 protein analytical and diagnostic
performances using a new automated capillary Western technology (Simple Western
technology-SW). For the validation of this assay, samples from a cohort of 268
patients suspected from sCJD were analyzed: 77 sCJD (including 40 definite sCJD)
and 191 non-CJD samples were tested using both SW and the current Western Blot
(WB) assays. Automated capillary Western determination provided better analytical
performances than WB with a lower intra- and inter-assay variability. Analytical
interferences such as hemolysis and high total protein concentration known to
lead to false positive WB results were also assessed using SW assay:
unfortunately, these interferences still remain confounders of CSF 14-3-3 protein
determination. Finally, automated capillary Western assay's sensitivity and
specificity were superior to those of WB assay (93.5 and 95.3%, respectively,
compared to 92.2 and 84.8% for WB). In conclusion, with a shorter time of
analysis than WB assays' (4 h versus 1.5 day), automated capillary Western assay
is an excellent routine alternative method to the currently performed WB assay
for CSF 14-3-3 protein detection in patients suspected of sporadic Creutzfeldt
Jakob disease.
PMID- 28509085
TI - Successful treatment of severe crescentic lupus nephritis by multi-target therapy
using tacrolimus and mycophenolate mofetil.
AB - Treatment of severe lupus nephritis (LN) has been controversial, and according to
recent guidelines and recommendations, cyclophosphamide still remains a first
line therapy. Herein, we present the case of a 37-year-old female patient who
developed rapidly progressive glomerulonephritis, which was histologically
diagnosed as class IV + V LN, with a large number of cellular to fibrocellular
crescents (62 % of glomeruli). Although the patient was considered to have the
most severe form of LN, complete remission was achieved within 6 months by multi
target therapy using tacrolimus and mycophenolate mofetil combined with
methylprednisolone pulse therapy. Our experience suggests that multi-target
therapy could be a potential treatment option for patients with severe crescentic
LN.
PMID- 28509086
TI - Reoperation after mitral valve repair in viewpoints of kidney injury as well as
hemolytic anemia.
AB - A 70-year-old woman developed anemia and kidney injury 10 months after mitral
valve (MV) repair. Serological findings and Doppler echocardiography suggested
hemolytic anemia due to mitral regurgitation jet collision with an annuloplasty
ring (MRCR). Since kidney injury persisted even without exacerbation of anemia
over 10 months, we performed an MV replacement. The anemia improved rapidly after
the surgery; however, the renal function remained chronic kidney disease (CKD)
after reoperation. Kidney injury was thought to be due to iron deposition and
decreased renal perfusion that caused tubular injury. A comprehensive literature
review shows that hemolysis due to MRCR in the early postoperative phase (within
3 postoperative months) can be often ameliorated with endothelialization without
the need for reoperation; however, hemolysis in the late postoperative phase can
persist even for a long period without reoperation. Chronic hemolysis can lead to
kidney injury and progress to CKD even without clinical evidence of exacerbation
of anemia. Therefore, in cases of late postoperative phase hemolysis, reoperation
should be considered for better management of kidney injury and hemolytic anemia.
PMID- 28509087
TI - Postoperative usage of tolvaptan in a patient with aortic valve stenosis
complicated by Child-Pugh classification B liver cirrhosis and hepatic edema.
AB - We report the case of an 80-year-old woman with postoperative congestive heart
failure (CHF) complicated by Child-Pugh classification B liver cirrhosis and
hepatic edema successfully treated with tolvaptan. The patient suffered from
liver cirrhosis and underwent partial hepatectomy for a hepatocellular carcinoma
diagnosed together with a severe aortic valve stenosis. Aortic valve replacement
was performed under cardiopulmonary bypass. The postoperative course was
uneventful until CHF and hepatic edema symptoms appeared on postoperative day
(POD) 2. The symptoms were treated with intravenous human atrial natriuretic
peptide and oral diuretics. As the condition showed no improvement, oral
tolvaptan was administered on POD 11 and thereafter, which markedly improved the
symptoms. This is apparently the first report describing the effectiveness of
tolvaptan for the postoperative management of fluid balance in a patient with
cardiac and liver dysfunction.
PMID- 28509088
TI - Repeated acute kidney injury associated with Mycobacterium gordonae infection.
AB - Mycobacterium gordonae is a nontuberculous mycobacterium widely distributed in
the environment. Although M. gordonae is not usually pathogenic and glomerular
lesions due to M. gordonae are very rare, infection has been reported in both
immunocompromised patients and healthy persons. We report a case of acute kidney
injury (AKI) in which M. gordonae was ultimately identified as the cause. A 70
year-old man was admitted to our hospital because of fever, polyarthritis, and
AKI. He was a hepatitis B virus carrier, suffered from diabetes, and had a past
history of erysipelas. No causative bacteria were identified, but coexisting
infection was suspected. The patient experienced remission with antibiotic
therapy, but the same symptoms recurred eight times. Blood polymerase chain
reaction was performed during the 7th recurrence, and M. gordonae was detected.
Clarithromycin was initiated, but 2 years after initial hospitalization, the
patient died due to M. gordonae infection. In this case, acute kidney injury was
a consequence of infection-related glomerulonephritis due to M. gordonae.
Mycobacterium is difficult to detect by routine culture methods; therefore,
diagnosis remains challenging.
PMID- 28509089
TI - Resolution of proteinuria after transarterial embolization of aberrant renal
artery in a patient with focal segmental glomerulosclerosis.
AB - A 24-year-old man was admitted to our hospital for persistent proteinuria. He was
born with a low birth weight but had grown up uneventful until the age of 20 when
he was found to have proteinuria. Because his body mass index was 30.9 kg/m2 at
that time, he was diagnosed as obesity-related nephropathy. However, weight
reduction and administration of ACE inhibitor were minimally effective for the
amelioration of proteinuria. Ultrasound-guided percutaneous renal biopsy at the
lower pole of right kidney was performed. As serious bleeding occurred from the
right aberrant renal artery soon after biopsy, he was treated with transarterial
embolization (TAE). The day after TAE, proteinuria completely disappeared. Renal
biopsy showed benign nephrosclerosis with secondary focal segmental
glomerulosclerosis (FSGS). Proteinuria could be induced by increased blood flow
and pressure due to abnormal blood supply from aberrant renal artery. This is the
first report of resolution of proteinuria after TAE of aberrant renal artery in a
patient with FSGS.
PMID- 28509090
TI - New-onset systemic lupus erythematosus in a long-term hemodialysis patient with
acute pleuritis and pneumonitis.
AB - A 61-year-old woman, with a 25-year history of maintenance hemodialysis due to
end-stage renal disease of unknown causes, was admitted because of systemic joint
pain and inflammatory response of unknown etiology that persisted for 1 month.
Laboratory data on admission revealed leukocytopenia, lymphocytopenia, high serum
C-reactive protein, and positivity for antinuclear antibody (ANA) and anti-double
strand DNA. After admission, she progressively developed cough and dyspnea. A
chest radiograph revealed bilateral ground glass opacity and pleural effusion. A
thoracentesis revealed lupus erythematosus cells, suggesting lupus pleuritis. A
chest computed tomography showed a pattern of diffuse alveolar damage compatible
with acute lupus pneumonitis. She fulfilled the American Rheumatism Association
diagnostic criteria for systemic lupus erythematosus (SLE). Methylprednisolone
pulse therapy followed by oral prednisone treatment improved the clinical
symptoms and laboratory abnormalities. ANA was negative 25 years earlier when she
first started hemodialysis and she had neither clinical nor serological
abnormalities related to SLE during the last 25 years. Further, she had neither
received drugs that can cause drug-induced SLE, nor had a history of ultraviolet
ray exposure, pregnancy, blood transfusion, trauma and smoking. This report
suggests that new-onset SLE can develop in patients undergoing long-term
dialysis. Hence, when we encounter dialysis patients with arthralgia and/or
respiratory disorders, we should consider the possibility of new-onset SLE.
PMID- 28509091
TI - Clinical remission of IgA nephropathy in an HIV-positive patient after combined
treatment with tonsillectomy and steroid pulse therapy.
AB - Various renal diseases other than human immunodeficiency virus (HIV)-associated
nephropathy, including IgA nephropathy (IgAN), have been recently reported to
cause chronic kidney disease and end-stage renal disease in HIV-infected
patients. The case of a 37-year-old HIV-infected male diagnosed as having IgAN
with proteinuria and microscopic hematuria that was successfully treated with
tonsillectomy and steroid pulse therapy in combination, resulting in
disappearance of urinary abnormalities (clinical remission), is reported, the
first such case in the literature. A renal biopsy revealed mesangial
proliferation associated with mesangial deposition of IgA and C3, consistent with
IgAN. Antiretroviral therapy and angiotensin receptor blocker therapy did not
improve his proteinuria. Therefore, he underwent tonsillectomy and steroid pulse
therapy, and clinical remission was successfully achieved with no opportunistic
infections. Clinical remission has continued for more than 3 years even after
discontinuation of steroid therapy. It appears that combined treatment with
tonsillectomy and steroid pulse therapy can be a good choice in managing HIV
infected patients with IgAN as long as secondary infection is strictly and
continuously monitored.
PMID- 28509092
TI - A case of primary (AL) amyloidosis with predominantly vascular amyloid deposition
in the kidney.
AB - We report a 70-year-old man with primary (AL) amyloidosis with predominantly
vascular deposition of amyloid diagnosed by renal biopsy, who was successfully
treated using two chemotherapy regimens. There was rapid elevation of the serum
creatinine level without remarkable proteinuria or hematuria. Renal histological
examination showed some thickened arterial walls with amyloid fibril
accumulation, and only a small amount of amyloid deposition in the glomeruli.
Immunohistochemical examination was positive for anti-kappa staining. Serum
immunoelectrophoresis and immunofixation testing did not show monoclonal
proteins, and urine immunoelectrophoresis did not show Bence-Jones proteins.
Serum free light chain (FLC) analysis showed that the serum FLC level and FLC
kappa/lambda ratio were abnormally high for his renal function. He received two
courses of VAD (vincristine, doxorubicin, and dexamethasone), followed by BD
(bortezomib and dexamethasone), resulting in a hematologic partial response.
Renal amyloidosis with vascular-limited amyloid deposition has few urinary
findings. Early diagnosis of this condition is challenging, because kidney
biopsies are not usually performed in patients without significant urinary
findings. We suggest several currently available methods of achieving earlier
detection of this condition.
PMID- 28509093
TI - A case of IgG4-related kidney disease complicated by eosinophilic lung disease.
AB - IgG4-related disease is a systemic chronic inflammatory disorder characterized by
a high blood level of IgG4 and the organ injuries by marked infiltration of IgG4
positive plasma cells and fibrosis. A 71-year-old male was hospitalized for a
cough, malaise and anorexia. IgG4-related disease was suspected due to marked
elevation of the serum IgG4 level. However, on lung biopsy, only eosinophil
infiltration was demonstrated with no plasma cell infiltration. Otherwise
abdominal contrast-enhanced CT showed mild enlargement of the bilateral kidneys
and many differed contrasted areas and FDG PET-CT. Moreover, renal biopsy
specimens showed typical tubulointerstitial nephritis with a large number of IgG4
positive plasma cells infiltration (the IgG4/IgG-positive cell rate, 89 %) and
fibrosis. We diagnosed this patient as typical IgG4-related kidney disease. He
was treated by the moderate dose of prednisolone (0.8 mg/kg/day) alone, and
showed prompt response in the clinical condition, and both the lung and kidney
lesions. In this case, it was useful for diagnosis of IgG4-related diseases to
evaluate an image such as abdominal contrast-enhanced CT and FDG PET-CT. Our case
might be one of the possible patterns of IgG4-related lung diseases. In addition,
we thought that there might be an association between hypereosinophilia and IgG4
related kidney disease.
PMID- 28509094
TI - Calciphylaxis induced by warfarin therapy in a patient with anti-phospholipid
antibody syndrome associated with systemic lupus erythematosus.
AB - Calciphylaxis is a life-threatening complication of end-stage kidney disease
(ESKD) and leads to cutaneous necrosis and gangrene. Various risk factors for
calciphylaxis have been reported, and warfarin therapy is a particularly strong
trigger. Here we report the case of 50-year-old woman with ESKD and systemic
lupus erythematosus who developed calciphylaxis after anti-thrombotic therapy,
including warfarin, for ischemic skin ulcers due to arteriosclerosis obliterans
and anti-phospholipid antibody syndrome. Although warfarin improved the
thrombotic skin ulcers, it might also be a trigger for calciphylaxis.
Discontinuation of the warfarin and the addition of low-density lipoprotein
apheresis and sodium thiosulfate infusion failed to improve the gangrene;
eventually, her legs had to be amputated to prevent lethal infection. The
histology of the dermal and soft tissue obtained from the amputated legs showed
typical findings of calciphylaxis. Warfarin is a vitamin K antagonist with
inhibitory effects on the calcification of regulatory proteins, such as matrix
Gla protein and fetuin-A. Therefore, the warfarin therapy might have induced
calciphylaxis in our patient.
PMID- 28509095
TI - A case of acute renal failure of multiple myeloma due to monoclonal type I
cryoglobulinemia with thrombotic microangiopathy.
AB - The term cryoglobulinemia (CG) is used to refer to vasculitis due to so-called
mixed cryoglobulins containing immune complexes. Although most cases of
monoclonal CG, called type I CG, are asymptomatic, purpura, skin ulcers, and
renal failure develop in some cases. Hematological disorders are the underlying
diseases in most cases, on which the therapeutic strategies available and the
prognosis of patients depends. We here report a case of a 47-year-old man who had
pain in both his ankles, with palpable purpura and epistaxis, and presented with
acute renal failure. Monoclonal immunoglobulin (Ig) G-kappa protein was detected
and cryoglobulin was also positive. Renal biopsy revealed emboli with a fibrillar
structure in the glomeruli and renal tubule lumina. The complication of
thrombotic microangiopathy (TMA) occurred during the course. Therefore, plasma
exchange and hemodialysis were added to methylprednisolone pulse therapy. The
treatment was successful, dissipating the purpura. However, the purpura relapsed
and renal dysfunction progressed when the administration of oral steroids was
tapered. Bone marrow biopsy was performed again, which indicated an increase in
abnormal plasma cells. The patient was finally diagnosed as multiple myeloma.
Then, bortezomib-dexamethasone therapy was initiated. This is the first case of
type I CG with monoclonal IgG complicated by TMA during the course; it provides
insight into the pathogenesis of renal dysfunction associated with type I CG.
PMID- 28509096
TI - Successful treatment by mycophenolate mofetil in a patient with focal segmental
glomerulosclerosis associated with posterior reversible encephalopathy syndrome.
AB - It has been reported that cyclosporine A (CsA) treatment may be associated with
posterior reversible encephalopathy syndrome. We report a 16-year-old man who
exhibited nephrotic syndrome and posterior reversible encephalopathy syndrome.
Intensive antihypertensive therapy restored him to consciousness. Renal biopsy
revealed that he suffered from focal segmental glomerulosclerosis. Although he
was treated with prednisolone and low-density lipoprotein apheresis therapy, his
proteinuria remained at high level. Then, mycophenolate mofetil (MMF) with less
influence on vessel endothelium compared with CsA and tacrolimus was
administered. Soon after, he reached remission of nephrotic syndrome without
recurrence of posterior reversible encephalopathy syndrome. This is the first
case that a young patient of focal segmental glomerulosclerosis with posterior
reversible encephalopathy syndrome achieved a complete remission by MMF treatment
without recurrence of posterior reversible encephalopathy syndrome. MMF may be
effective for young patients of focal segmental glomerulosclerosis especially
with clinical condition of vascular endothelial damage such as posterior
reversible encephalopathy syndrome.
PMID- 28509097
TI - Propylthiouracil-associated rapidly progressive crescentic glomerulonephritis
with double positive anti-glomerular basement membrane and antineutrophil
cytoplasmic antibody: the first case report.
AB - We report a case of propylthiouracil (PTU)-induced double antineutrophil
cytoplasmic antibody (ANCA) and anti-glomerular basement membrane antibody (anti
GBM antibody) disease causing pulmonary-renal syndrome in a 35-year-old Thai
woman with 10-year history of PTU treatment for thyrotoxicosis. She developed
clinical symptoms of vasculitis upon receiving long-term PTU treatment.
Prednisolone treatment and the switching from PTU to methimazole resulted to
short-term clinical improvement. Nevertheless following termination of steroid
treatment, she developed recurrent pulmonary hemorrhage and rapidly progressive
glomerulonephritis. The kidney biopsy showed crescentic glomerulonephritis with
linear IgG deposit on the glomerular basement membrane although transbronchial
lung biopsy showed no immune deposit along the alveolar basement membrane. Serum
testing for p-ANCA was positive and western blot showed positive antibody to the
alpha-3 chain of collagen type IV. Both ANCA and anti-GBM antibody may play a
role in the development of end organ damage. To facilitate early and specific
intervention, clinicians should be aware of the propensity of PTU to cause lupus
like syndromes with renal involvement. In patients with PTU-induced ANCA
associated glomerulonephritis, serum anti-GBM antibody test may be useful in the
early diagnosis of double positive antibodies disease and plasmapheresis should
be performed without delay.
PMID- 28509098
TI - HBV reactivation in a patient on chronic haemodialysis treatment.
PMID- 28509099
TI - A case of acute kidney injury due to secondary retroperitoneal fibrosis caused by
direct invasion of esophageal squamous cell carcinoma.
AB - A 71-year-old man who developed renal failure was admitted to our hospital.
Computed tomography without contrast enhancement showed bilateral hydronephrosis
together with a soft tissue mass around the abdominal aorta, leading to the
diagnosis of retroperitoneal fibrosis. Serum levels of immunoglobulin G4 were
within the normal range. The patient was then evaluated for the presence of
undiagnosed malignancy as a possible cause of secondary retroperitoneal fibrosis.
Upper gastrointestinal tract endoscopy demonstrated esophageal cancer. Histology
of the esophageal lesion and the retroperitoneal mass showed squamous cell
carcinoma (SCC). Therefore, the retroperitoneal fibrosis was considered to be due
to the invasion of SCC of the esophagus, and chemotherapy was chosen as the
treatment. This is the first case report of postrenal failure due to secondary
retroperitoneal fibrosis caused by the direct invasion of esophageal SCC.
Physicians should be aware of occult malignancy as the cause of unexplained
retroperitoneal fibrosis, even clinically silent, to avoid inappropriate
management or delay in the treatment of potentially life-threatening co
morbidities.
PMID- 28509100
TI - Erratum to: Reoperation after mitral valve repair in viewpoints of kidney injury
as well as hemolytic anemia.
PMID- 28509101
TI - Effectiveness of plasma exchange for acquired type A hemophilia.
AB - An 80-year-old man was treated at our hospital for chronic kidney disease,
diabetes mellitus and hypertension. He presented a bleeding tendency over the
past several weeks. When he was admitted to our hospital with a consciousness
disturbance, he had irregular 10-20 cm patches of subcutaneous bleeding.
Laboratory findings showed prolonged activated partial thromboplastin time (APTT)
but normal platelet count and prothrombin time. The administration of fresh
frozen plasma did not control the bleeding tendency and the result of APTT cross
mixing test suggested the presence of factor VIII inhibitor. The diagnosis of
acquired hemophilia A was made by a marked decrease in factor VIII activity
levels (<1 %) and a high titer of factor VIII inhibitor (11 Bethesda units). To
remove the factor VIII inhibitor and suppress its production, plasma exchange was
performed and methylprednisolone was administered. Thereafter, the bleeding
tendency could be controlled with APTT measurement normalization. Plasma exchange
does not have a first priority in the treatment but our case findings suggested
that plasma exchange is an effective method for eliminating factor VIII inhibitor
and alleviating acquired hemophilia A severity.
PMID- 28509102
TI - Pediatric Sjogren syndrome with distal renal tubular acidosis and autoimmune
hypothyroidism: an uncommon association.
AB - A 14-year-old female came with the history of sudden onset weakness; during work
up, she was found to have hyperchloremic metabolic acidosis with normal anion gap
and normal renal function suggesting the possibility of renal tubular acidosis
(RTA). On further evaluation of RTA, she had positive antinuclear antibody, anti
Ro, and anti-La antibodies. On nuclear scan of salivary glands, her left parotid
gland was nonfunctional. Her parotid biopsy revealed dilated interlobular ducts
engulfed by lymphoid cells. She also had autoimmune hypothyroidism as suggested
by raised TSH and positive anti-TPO antibodies. At admission, her serum potassium
levels were low and she was treated with intravenous potassium chloride. After
she recovered from acute hypokalemic paralysis, she was started on oral potassium
citrate along with phosphate supplements, hydroxychloroquine, oral prednisolone
and thyroxine supplements. Over the next 6 months, she has significant reduction
in the dosage of potassium, bicarbonate and phosphate and gained 3 kg of weight
and 3.5 cm of height. As primary Sjogren syndrome itself is rare in pediatric
population and its association with renal tubular acidosis is even rarer, we
suggest considering Sjogren syndrome as a differential diagnosis during the RTA
work-up is worth trying.
PMID- 28509103
TI - Combined IgG4kappa and IgG1lambda deposition in the glomerular and tubular
basement membrane accompanied by autoimmune neutropenia (AIN) and immune
thrombocytopenia (ITP).
AB - A 48-year-old male was admitted to our hospital with nephrotic syndrome. Light
microscopic examination of a renal biopsy specimen showed almost normal
glomerular appearance, however, immunofluorescence examination revealed linear
and granular IgG deposits on the glomerular basement membrane (GBM), accompanied
by slight IgG deposition in the tubular basement membrane (TBM). Further
investigation of the IgG subclass and light chain staining revealed that the
glomerular deposits were composed of IgG1 and IgG4, with both kappa and lambda
light chains, while the tubular deposits were composed of only IgG4 and kappa
light chains. The electron-microscopic findings of small granular deposits in the
GBM and TBM closely resembled those of light and heavy chain deposition disease
(LHCDD). Immunoelectron microscopy confirmed the presence of kappa and lambda
chains in the GBM and TBM, however, only significant kappa chain deposition was
found in the TBM. There was no evidence of monoclonal gammopathy. Clinically, the
patient subsequently developed neutropenia and thrombocytopenia associated with
the presence of anti-neutrophil antibody and anti-GPIIb/IIIa antibody-producing B
cells in the blood. Oral steroid administration was initiated, which led to
amelioration of the neutropenia, thrombocytopenia and proteinuria. This may be a
very rare case of combined IgG4kappa and IgG1lambda deposition disease
accompanied by autoimmune neutropenia (AIN) and immune thrombocytopenia (ITP)
suggestive of biclonal immunoglobulin deposition disease (BIDD). Investigation of
the IgG subclass and of the light chains was useful for recognizing the clonality
of the immunoglobulin deposits in the kidney.
PMID- 28509104
TI - Autosomal dominant distal renal tubular acidosis caused by a mutation in the
anion exchanger 1 gene in a Japanese family.
AB - Autosomal dominant distal renal tubular acidosis (dRTA) is a rare disorder caused
by a mutation in the AE1 gene encoding the chloride-bicarbonate (Cl-/HCO3-) anion
exchanger 1 (AE1). Most patients with this disorder present with clinical
symptoms in adulthood and their phenotype is milder than that of those with
autosomal recessive dRTA. In this report, we describe a Japanese family with
autosomal dominant dRTA in which the mother and her daughter presented with
severe symptoms caused by hypokalemia at 2 years of age. The heterozygous AE1
mutation G609R, which is a known causative mutation of dRTA, was identified in
both patients. To our knowledge, this is the first report of a Japanese family
with autosomal dominant type dRTA caused by an AE1 mutation. We, therefore,
propose that alterations of AE1 should be considered causative of autosomal
dominant dRTA even if typical symptoms appear during early childhood and the
clinical features are severe.
PMID- 28509105
TI - Acute kidney injury caused by sarcoid granulomatous interstitial nephritis
without extrarenal manifestations.
AB - Granulomatous interstitial nephritis (GIN) is one of the renal pathological
manifestations of sarcoidosis. It is usually clinically silent, but may present
occasionally as acute kidney injury (AKI). AKI caused by sarcoid GIN without
extrarenal manifestations is extremely rare. We report a case of a 70-year-old
man with a history of type 2 diabetes mellitus admitted with progressively
worsening kidney function. The patient also exhibited anorexia, malaise and
weight loss. Laboratory tests showed an elevated serum lysozyme level, but the
serum angiotensin-converting enzyme (ACE) and serum calcium levels were normal.
Increased uptake was evident only in kidney on gallium 67 scintigraphy. Although
typical organ involvement of sarcoidosis was not evident, a renal biopsy showed
granulomatous interstitial nephritis with non-caseating granulomas. No
medications had been added in the 3 years preceding renal function deterioration.
Following a bronchoalveolar lavage that revealed a high CD4:CD8 ratio, and a skin
test that showed negative for tuberculin, a diagnosis of renal sarcoidosis was
established. On diagnosis, oral prednisolone was initiated and renal function
improved. The anorexia and malaise also disappeared. This is the extremely rare
case of AKI caused by sarcoid GIN without extrarenal manifestations or elevated
serum ACE level.
PMID- 28509106
TI - Posterior reversible encephalopathy syndrome in a uremic patient with autosomal
recessive polycystic kidney disease.
AB - Posterior reversible encephalopathy syndrome (PRES) is characterized by headache,
seizures, altered mental status, and visual disturbance. It is diagnosed by the
presence of both clinical symptoms and radiographic findings on the parietal
occipital lobes. We here report a 61-year-old woman with non-compensative liver
cirrhosis and chronic kidney disease, presenting with uremia-induced PRES. She
expressed loss of consciousness and subsequent visual disturbance, during the
progression of uremia. She was treated with hemodiafiltration therapy, and the
symptoms of PRES fully improved. The case is of particular interest, in that the
appearance of abnormal findings on magnetic resonance imaging was delayed more
than 2 weeks, as compared to that of clinical symptoms. The etiology of chronic
kidney disease in the patient was considered to be autosomal recessive polycystic
kidney disease, and we performed DNA sequencing analysis on the polycystic kidney
and hepatic disease 1 gene. Two homozygous missense mutations were found in the
patient and may combinatorially affect the disease. This case raises a
possibility that the incidence of PRES is much higher if the radiological
examination is performed more frequently.
PMID- 28509107
TI - Concurrent acute spontaneous tumor lysis syndrome complicated with multiple organ
failure in a patient with pre-existing undiagnosed lung cancer.
AB - Acute kidney injury, a common complication associated with malignancy, occurs in
various clinical situations for numerous reasons. Acute tumor lysis syndrome
(TLS) is possibly the most significant cause of acute kidney injury in cancer
patients, because it is fulminant at onset and associated with severe metabolic
derangements. Acute spontaneous tumor lysis syndrome is rare and most of the
related malignancies belong to hematologic malignancies but it has seldom been
investigated as bulky or advanced metastatic non-hematologic malignancies. TLS
comprises a clinical laboratory derangement of cellular metabolism which can lead
to acute renal impairments, cardiac arrhythmia, seizures and patient demise.
Prevention and treatment of tumor lysis syndrome depends on early recognition of
at-risk patients, volume repletion and xanthin oxidase inhibitors. In addition,
in patients with high risk tumor types, prophylactic use of rasburicase before
chemotherapy is required. If dialysis is required, continuous modalities may be
favored, particularly in patients with more severe TLS. This case report
discusses a 79-year-old man with controlled Alzheimer's disease presented with
picture of septic shock and multiorgan dysfunction (acute kidney injury, acute
lung injury, acute brain injury) pulmonary suppuration in the right lung field
due to aspiration pneumonia with infection-induced systemic inflammatory response
(SIRS) was diagnosed. Further work-up revealed lung cancer on chest CT scan.
Antibiotic, respirator and hemodialysis treatment improved his condition but died
several days later. Acute spontaneous TLS may present in association with
infectious SIRS and multiple organ failure, the combination of which results in
significant mortality.
PMID- 28509108
TI - Simultaneous nephrotic syndrome and hepatitis in secondary syphilis: case report
and review of the literature.
AB - A 66-year-old man presented with a penile ulcer, an acute clinical onset of
nephrotic syndrome and hepatitis. Secondary syphilis was diagnosed on the basis
of the history of rash and the result of strongly positive serological test for
syphilis. A renal biopsy demonstrated membranous glomerulonephritis with
subepithelial electron-dense deposits. After treatment with amoxicillin for 2
weeks, he achieved clinical recovery. It is important to recognize syphilis as a
reversible cause of nephrotic syndrome and acute hepatitis because antibiotic
therapy can result in complete remission.
PMID- 28509109
TI - A case of acute EPS with local cocoon formation in a patient on peritoneal
dialysis.
AB - Encapsulating peritoneal sclerosis is a rare and life-threatening complication of
long-term peritoneal dialysis and until now there is no established medical
treatment. Many factors have been incriminated in its pathogenesis but they do
not explain all risk conditions. We report our experience and we investigate the
predisposing factors. Probably unidentified factors make some patients more
susceptible to developing encapsulating peritoneal sclerosis.
PMID- 28509110
TI - Prominent hyperplasia of renin-producing juxtaglomerular apparatus after chronic
and complete blockade of the renin-angiotensin system in adult IgA nephropathy.
AB - Juxtaglomerular apparatus (JGA) hyperplasia rarely happened in renal biopsy and
has been controversial clinically, because synthesis and secretion of renin were
susceptible to the effect of clinical condition and medication. Here we present
the case of a 39-year-old who got JGA hyperplasia of IgA nephropathy (IgAN) after
long-term inhibition of the renin-angiotensin system (RAS) with an angiotensin
receptor blocker (ARB), and a direct renin inhibitor (DRI) in combination with a
diuretic. He was diagnosed with IgAN in his first renal biopsy, and was treated
with supra-maximal dosages of ARB, DRI and a diuretic. In the second biopsy,
because of the massive proteinuria and occurrence of steroid-induced diabetes, it
was revealed that the area and the number of JGA cells were strikingly increased
in observed glomeruli. Immunohistopathologically, the both specimens were stained
by human renin antibody. The hyperplastic JG cells contained a large amount of
renin granules. Putative renin granules were observed in some interstitial cells
adjacent to an afferent arteriole by electron microscopy. The increasing response
of renin granules co-localized in prominent JGA hyperplasia should be worried
while physicians treat hypertensive patients with potent RAS inhibitors and
diuretics even though they have diabetes. This is the first report showing a
clinical course of forming prominent JGA hyperplasia directly after a full
combination of RAS inhibitors and diuretics in adult IgA nephropathy.
PMID- 28509112
TI - Response to the Letter to the Editor by Arndt van Ophoven.
PMID- 28509113
TI - Re: Management of device-related complications after sacral neuromodulation for
lower urinary tract disorders in women: a single center experience : Tilemachos
Kavvadias, Markus Huebner, Sara Yvonne Brucker, Christl Reisenauer.
PMID- 28509111
TI - Synchrony effect on joint attention.
AB - Research on joint attention has demonstrated that individuals are sensitive to a
coactor's attentional relation to jointly attended stimuli. Within a
chronobiological approach, a study was conducted to assess whether the presence
of joint attention, as measured by the joint Navon effect, was influenced by the
synchrony effect. Pairs of participants sitting next to each other were required
to respond to the identity letters in a go/no-go Navon task. The joint Navon task
was performed by morning, intermediate and evening types (81 pairs) at different
times of day (09:00-10:00; 13:00-14:00; 17:00-18:00). The joint Navon effect on
task performance was highlighted at the optimal time of day (in the morning for
morning types, in the early afternoon for intermediate types and in the evening
for evening types), but it disappeared or decreased at the non-optimal time of
day, with the exception of evening types. The results demonstrated that joint
attention was affected by the synchrony effect.
PMID- 28509115
TI - Erratum to: Valorization of Proteins from Co- and By-Products from the Fish and
Meat Industry.
PMID- 28509114
TI - Implicating the potential role of orexin in hypertension.
AB - Orexins (orexin A and orexin B), neuropeptides of hypothalamic origin also known
as hypocretins, have been well documented for regulating the different
physiological functions including feeding, sleep wakefulness, stress, and reward.
However, from the past few years, orexins have evolved as an emerging biomarker
for various endocrine disorders including diabetes mellitus and obesity which
ultimately leads to various cardiovascular risk factors. Orexins exist in two
isoforms orexin A and orexin B and exert their effect by acting on the G protein
coupled receptors orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R).
Furthermore, localization of orexinergic neurons in the different brain regions
has been involved in regulating the cardiovascular and sympathetic activity.
Growing evidences have addressed the potential role of orexins including orexin A
and orexin B in modulating the hypertension via exerting their effect on the mean
arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity
(RSNA). The present review summarizes the central role orexins in the
hypertension along with the possible mechanism.
PMID- 28509118
TI - Anti-glomerular basement membrane disease accompanied by systemic lupus
erythematosus presenting central nervous system involvement.
AB - We report a case of rapidly progressive glomerulonephritis caused by anti
glomerular basement membrane (GBM) disease accompanied by systemic lupus
erythematosus (SLE) presenting central nervous system involvement in a 32-year
old Japanese male. He was admitted to our hospital because of a 3-week history of
fever and rapidly failing renal function requiring hemodialysis (HD). Laboratory
tests showed anti-GBM antibody elevation with a value of 16,385 units/ml. On day
85, he had generalized tonic-clonic seizure. Brain magnetic resonance T2 Flair
imaging showed multiple high intensity lesions in a broad area. We made a
diagnosis of central nervous system involvement in SLE based on positivity for
antinuclear and anti-DNA antibodies, hypocomplementemia, and discoid skin rash.
After combined therapy consisting of plasma exchange, HD, and steroid pulse, the
patient made a good recovery without any residual neurological sequelae, though
kidney dysfunction requiring maintenance HD remained. Anti-GBM antibody finally
became undetectable on the 144th hospital day.
PMID- 28509116
TI - Tonic regulation of stationary asynchronous firing of a neural network.
AB - The impact of tonic conductance upon population activity was investigated. An
extra tonic transmembrane current through GABA-activated extrasynaptic GABA A
receptors was found to control stationary asynchronous firing both quantitatively
and qualitatively. Quantitative regulation consisted in alterating a current
level of stationary population activity while qualitative regulation manifested
itself in appearance of resilient asynchronous spiking in case GABA reversal
potential exceeded a certain threshold. The study was based on a modified rate
model after Wilson and Cowan and backed up with a computer simulation of an
explicit network model.
PMID- 28509117
TI - The theory of multiple stupidities: education, technology and organisation in
Arabia.
AB - Traditional perspectives have envisaged intelligence as one entity dominated by a
single set of abilities (i.e. cognitive abilities), whereas modern perspectives
have defined intelligence in various shapes (e.g. linguistic, musical and
interpersonal intelligences). By the same token, traditional perspectives have
examined stupidity as one set of inabilities (i.e. cognitive inabilities).
However, it is not clear whether modern perspectives have discussed whether
stupidity exists in various forms-in the same way as they have envisaged
intelligence. To address this limitation, 257 university members were asked to
share what they perceived as being stupid educational and technological practices
in their institutions. Analysis of the data suggested three concepts were
important to the members: moral, spatial and administrative stupidities. That is,
stupidity is perceived to come in the form of failing to meet certain moral,
spatial and administrative values. This implies that modern perspectives may
conceptualise stupidity differently from traditional perspectives, seeing it as
going beyond cognitive inabilities and viewing it as existing in various forms
(e.g. moral, spatial and administrative stupidities). Thus, there are multiple
stupidities as there are multiple forms of intelligence. A strength of this
research is that it views stupidity through an organisational and qualitative
lens, although some may traditionally expect such a topic to be examined
quantitatively through psychometric and biological approaches.
PMID- 28509119
TI - Serial sonographic findings during progression from acute pyelonephritis to renal
abscess: a rare case report.
AB - Renal abscess, accumulation of infective fluid in the kidney, is a rare
pathology. Currently, no reports of the serial imaging changes of acute
pyelonephritis (APN) progressing to renal abscess exist. We report clinical and
serial sonographic findings of a patient with hyper-immunoglobulin E syndrome, a
primary immunodeficiency, who developed APN that progressed to renal abscess.
Renal ultrasonography revealed that echogenicity of infectious lesions
dramatically changed from isoechoic to hyperechoic and to hypoechoic during
progression. These findings are useful for differential diagnosis of APN, acute
focal bacterial nephritis, and renal abscess.
PMID- 28509120
TI - Complex glomerular pathology of thrombotic microangiopathy and focal segmental
glomerulosclerosis forms tumor-like mass in a renal transplant donor with severe
renovascular hypertension.
AB - The pathogenesis of glomerular hypertension-mediated FSGS and its histological
variations in humans remains unknown. A 47-year-old man developed nephrotic
syndrome, renal dysfunction, and malignant hypertension 2 years after donating a
kidney to his son. The donor's remnant kidney developed renal mass at an upper
pole which was fed by an aberrant artery that branched from the root of the renal
artery. Furthermore, the main non-aberrant renal artery demonstrated severe
stenosis that caused renovascular hypertension, resulting in malignant
hypertension. Upon radiological examinations, a tumorous mass was detected.
Because of progressive renal dysfunction, nephrectomy was performed. The kidney
revealed a diffuse distribution of complex FSGS lesions, i.e., a random
combination of cellular/collapsing FSGS and glomerular thrombotic
microangiopathy, confined to the renal mass, whereas such lesions were absent in
the non-mass portion. This indicated that severe glomerular hypertension alone
caused FSGS with TMA features. Heterogeneous FSGS lesions let us surmise that
glomerular hypertension promoted simultaneous damages in endothelial cells and
podocytes, which synergistically progressed to glomerulosclerosis. This unique
case uncovers causal relationships between unusual glomerular hypertension and
severe forms of FSGS that was possibly caused by the disruption of homeostasis
sustained by podocytes and endothelial cells.
PMID- 28509121
TI - Antithyroid drug-associated MPO-ANCA-positive tubulointerstitial nephritis in a
type 2 diabetes patient: a case report.
AB - A 54-year-old man diagnosed with type 2 diabetes and hyperthyroidism was
prescribed propylthiouracil (PTU) after the patient developed hepatic dysfunction
on thiamazole. At 50 mg/day of PTU, he was stable with thyroid-stimulating
hormone receptor and thyrotropic antibody titers remaining stable. After four
years of taking PTU, he was referred to the Department of Nephrology due to a
rapid increase in his serum creatinine (Cr) level. He showed impaired renal
function (Cr 2.26 mg/dL; estimated glomerular filtration rate (eGFR), 25 mL/min).
In addition, urinary beta2-microglobulin (beta2 MG) was increased to 71,980 MUg/L
and was positive for myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody
(ANCA) (33.9 U/mL). Gallium scintigraphy demonstrated a remarkable accumulation
in both kidneys. The patient was diagnosed with tubulointerstitial nephritis
based on a renal biopsy, the results of which suggested that it might have been
induced by PTU. He was treated with prednisolone (PSL) at 30 mg/day. As a result,
within two weeks, Cr, eGFR, and urinary beta2 MG levels were progressively
improved to 1.72 mg/dL, 34 mL/min, and 22,020 MUg/L, respectively. Therefore, we
tapered off the PSL with a dose of 5 mg/day after approximately one year. There
have been no exacerbated renal function parameters. Although there are many
reports on patients developing MPO-ANCA-positive crescentic glomerulonephritis
after the administration of PTU, we report on a relatively rare case in which
interstitial nephritis occurred after the administration of PTU.
PMID- 28509122
TI - Severe hyponatremia in a patient with schizophrenia associated with prolonged
consciousness disturbance.
AB - Hyponatremia presents with various central nervous system symptoms during its
course and treatment. We treated a patient who presented with a prolonged
consciousness disorder and was suspected of having complications of neuroleptic
malignant syndrome and osmotic demyelination syndrome (ODS) during the treatment
for his hyponatremia, which was caused by syndrome of inappropriate secretion of
antidiuretic hormone (SIADH). The patient was a 30-year-old Japanese man who had
been under treatment for schizophrenia. He presented with profound hyponatremia
(96 mEq/L) and a consciousness disorder. Because he was taking a number of
antipsychotic drugs and since psychogenic polydipsia was present along with
laboratory findings, the patient was diagnosed with SIADH. However, the
consciousness disorder reappeared after his serum sodium concentrations were
normalized, and it persisted over a long period. Although ODS was suspected from
the clinical course and imaging findings, there were several inconsistencies,
such as the lack of quadriplegia. The patient also showed muscular rigidity and
fever, and we, therefore, diagnosed complications of malignant hyperthermia
syndrome caused by the discontinuation of all antipsychotic drugs at the time of
onset. There have been no reports of complications of these two conditions, and
we report this case for its clinically valuable information.
PMID- 28509123
TI - Serum calcitriol levels in a patient with X-linked hypophosphatemia complicated
by autosomal dominant polycystic kidney disease.
AB - Serum calcitriol [1,25(OH)2D] levels are low normal in the presence of
hypophosphatemia in X-linked dominant hypophosphatemic rickets (XLH) due to
elevated serum fibroblast growth factor 23 (FGF23) levels. We report a peculiar
finding of markedly elevated serum 1,25(OH)2D levels in a patient with XLH
complicated by autosomal dominant polycystic kidney disease (ADPKD) and retinitis
pigmentosa (RP). She was diagnosed with XLH, ADPKD and RP at the age of 5, 13 and
15 years, respectively. After the diagnosis of ADPKD, the 1,25(OH)2D levels
increased up to 282 pg/mL treated with a pharmacological dose of 1alphaOHD3
(1alphaOHD3). At the age of 17 years, under a physiological dose, serum 25
hydroxyvitamin D3 (25OHD3) and 1,25(OH)2D levels were 14.0 ng/mL and 93 pg/mL,
respectively. With off-therapy for 3 days, the latter decreased to 9 pg/mL with
an increased ratio of 24,25-dihydroxyvitamin D3 (24,25(OH)2D3)/25OHD3. Serum
FGF23 and circulating soluble alpha-klotho (sKlotho) levels were 552 and 873
pg/mL, respectively, with the latter being almost half of the normal control.
Since the coexistence of elevated serum FGF23 and 1,25(OH)2D levels contradicted
the conventional FGF23 actions, we speculated on the possible association of
decreased sKlotho with the peculiar vitamin D metabolism, although mechanisms in
detail remained unknown.
PMID- 28509124
TI - Metastatic renal cell carcinoma with undetectable renal mass presenting as
lymphadenopathy.
AB - Renal cell carcinoma has the ability to metastasize to any organ; about 16 % of
affected patients present initially with metastasis. However, it is rare for this
tumor to present with metastasis from an unidentified primary. The current use of
immunohistochemistry and molecular genetics has enabled clinicians to reach a
precise diagnosis. It has been hypothesized that the treatment protocol for
metastatic renal cell carcinoma can be applied to cases with undetectable
primary. In this paper, a novel case of metastatic renal cell carcinoma
presenting with lymphadenopathy with no evidence of a primary renal lesion is
reported from Kuwait cancer center.
PMID- 28509125
TI - A case of PR3-ANCA-positive anti-GBM disease associated with intrarenal arteritis
and thrombotic microangiopathy.
AB - Coexistence of anti-glomerular basement membrane (anti-GBM) disease with anti
neutrophil cytoplasmic antibody (ANCA) is occasionally reported and termed
"double positive" disease. Interestingly, the majority of "double positive" ANCA
is myeloperoxidase (MPO)-ANCA, and some of the MPO-ANCA-positive cases reveal
intrarenal arteritis indicating an ANCA-associated renal lesion. In contrast,
proteinase 3 (PR3)-ANCA-positive "double positive" disease had rarely been
reported, and as far as we know, none of the cases showed intrarenal arteritis.
Herein, we report a case of PR3-ANCA-positive "double positive" anti-GBM disease
presenting with pulmonary-renal syndrome and hemolytic uremic syndrome. The
kidney biopsy showed crescentic glomerulonephritis, intrarenal arteritis, and
thrombotic microangiopathy. This case newly describes PR3-ANCA-associated
intrarenal arteritis in "double positive" anti-GBM disease.
PMID- 28509126
TI - Gram-negative sepsis following biopsy of a transplant recipient with asymptomatic
allograft pyelonephritis.
AB - Pyelonephritis post-renal transplantation is common and in up to 50% of cases can
be asymptomatic. Transplant pyelonephritis shares a lot of histopathological
features with acute cellular rejection. We present a case of asymptomatic acute
graft pyelonephritis where a renal biopsy was complicated by sepsis, and discuss
the difficulties in interpretation of renal histology in the setting of
transplant pyelonephritis where rejection may also be a possibility, but
differentiation is challenging.
PMID- 28509127
TI - Membranous glomerulonephropathy in a patient with bullous pemphigoid.
AB - Bullous pemphigoid (BP) is a common autoimmune blistering disease that can be
complicated by autoimmune disorders. We describe a patient with BP who developed
membranous glomerulonephropathy (MN). Proteinuria decreased during the clinical
course as anti-BP180 antibody titers decreased. This finding suggested an
association between the pathogenesis of these two diseases in terms of
immunological disorders.
PMID- 28509128
TI - A case of rapid amelioration of hepatitis C virus-associated cryoglobulinemic
membranoproliferative glomerulonephritis treated by interferon-free directly
acting antivirals for HCV in the absence of immunosuppressant.
AB - Mixed cryoglobulinemic syndrome, which is a systemic vasculitis characterized by
the immune complex deposition in small- and medium-sized arteries and most often
due to chronic hepatitis C virus (HCV) infection, sometimes clinically manifests
as refractory glomerulonephritis or nephritic syndrome. Patients with mixed
cryoglobulinemic nephropathy who have a rapidly progressive glomerulonephritis
should receive immunosuppressive therapy. After disease stabilization, patients
should receive concurrent therapy for the underlying HCV infection. The standard
therapy of a chronic HCV infection is IFN monotherapy or IFN combined with
ribavirin; however, after the introduction of direct-acting antivirals (DAAs),
the standard therapy for patients with HCV genotype 1 has dramatically changed.
We report a case of HCV-associated cryoglobulinemic membranoproliferative
glomerulonephritis (MPGN) successfully treated by daclatasvir and asunaprevir,
which are IFN-free DAAs for HCV, in combination with angiotensin II receptor
blocker without immunosuppressive therapy. The patient developed severe nephrotic
syndrome with progressive kidney dysfunction. Blood examination revealed a high
copy number of HCV-RNA (6.4 log IU/mL, type 1), cryoglobulinemia, paraproteinemia
of IgM-kappa, and hypocomplementemia. Histological analysis showed MPGN type 1.
These findings were compatible with those observed in HCV-associated
cryoglobulinemic MPGN. This case offers original evidence for the application of
newer generation of IFN-free DAAs in the treatment of HCV-associated
cryoglobulinemic nephropathy.
PMID- 28509129
TI - Successful long-term effects of direct renin inhibitor aliskiren in a patient
with atherosclerotic renovascular hypertension.
AB - A 64-year-old man visited our hospital with complaints of misty vision and
ophthalmalgia. On admission, his blood pressure (BP) was high at 220/135 mmHg
with no past history of hypertension, and he had choked discs. He was tentatively
diagnosed as having idiopathic intracranial hypertension, and was later found to
have atherosclerotic unilateral renovascular hypertension (RVH) based upon the
extremely high plasma renin activity together with the radiological image tests.
On day 3, combined antihypertensive therapies consisting of oral angiotensin II
receptor blocker (ARB) and Ca channel blocker (CCB) along with intravenous CCB
induced an abrupt BP lowering which led to deterioration of his renal function,
progressing into acute kidney injury (AKI). Cessation of the ARB and reduction of
the CCB dose ameliorated the AKI-related decline in renal function. On day 17, as
he was reluctant to receive surgical intervention, he was treated with a direct
renin inhibitor, aliskiren, combined with a half-dose CCB as a maintenance
antihypertensive therapy. The therapy has proven not only successful to
chronically maintain his renal function but was also capable of controlling his
BP in the neighborhood of 130/85 mmHg over a period of 2 years. The present case
suggests that the direct renin inhibition with aliskiren can be a safe and useful
antihypertensive option to control hypertension and to preserve renal function in
patients with atherosclerotic unilateral RVH.
PMID- 28509130
TI - Acute pulmonary thromboembolism occurring during treatment with tolvaptan in a
patient with autosomal-dominant polycystic kidney disease.
AB - Autosomal-dominant polycystic kidney disease (ADPKD) is the most prevalent cystic
kidney disease, with approximately half of the patients reaching end-stage renal
disease by the age of 60. Tolvaptan prevents renal cyst growth by inhibiting
intracellular cyclic AMP and is recommended for patients with ADPKD. Reports of
thrombotic complications with tolvaptan have been limited. We report a case of a
60-year-old man who developed thromboembolisms during tolvaptan treatment for
ADPKD. The patient started tolvaptan in July 2014. He was brought to our hospital
in February 2015 with a sudden onset of dyspnea and chest pain after 6 days of
persistent watery diarrhea. Blood tests revealed enhanced coagulation and
fibrinolysis, and contrast-enhanced computed tomography confirmed the presence of
multiple thromboembolisms. Venous thromboembolism (VTE) with acute pulmonary and
lower extremity thrombi was diagnosed, and the patient was immediately admitted.
Tolvaptan was discontinued on admission, and intravenous fluid loading and
monteplase were started. Subsequently, chest pain and dyspnea resolved, with
thrombi resolution occurring by day 14; the patient was discharged on day 18 in
stable condition. VTE was attributed to continued tolvaptan during diarrhea and
dehydration; tolvaptan itself was not associated with enhanced coagulability.
Dehydrated patients with ADPKD, such as the patient in this case, are at an
increased risk for thrombus formation. Proper education should be provided to
maintain appropriate fluid status and discontinue tolvaptan upon volume
depletion.
PMID- 28509131
TI - Growth hormone therapy for a patient with idiopathic Fanconi syndrome and growth
hormone deficiency.
AB - Idiopathic Fanconi syndrome (FS) is characterized by a generalized dysfunction of
the renal proximal tubules. Patients with FS often exhibit growth retardation due
to complex factors, such as hypophosphatemia, metabolic acidosis, disturbed
vitamin D metabolism and hypokalemia. To date, one FS patient has been reported
to exhibit growth failure due to growth hormone deficiency (GHD), but the long
term clinical course of recombinant human GH (rhGH) therapy has not been
reported. At 10 months of age, the patient was admitted to our hospital due to
growth failure. Blood and urinary biochemical abnormalities, such as
hypophosphatemia, metabolic acidosis, glycosuria and low-molecular-weight
proteinuria, indicated a generalized dysfunction of the renal proximal tubules.
The presence of cystinosis, collagen diseases, toxic agents and metabolic
diseases were excluded. These features are compatible with idiopathic FS.
Treatment with high-dose alkali, potassium citrate, phosphate buffer,
hydrochlorothiazide and vitamin D supplement was initiated. The biochemical
abnormalities achieved nearly normal values, and the patient's height was within
2.5 SD at the age of 2 years. However, his height did not continue to increase at
the same rate and gradually declined to -2.9 SD at 4 years of age. GH stimulation
test demonstrated GHD. After initiation of rhGH therapy, his height improved to
2.0 SD at the age of 9 years with no adverse effects. In conclusion, we report
the case of a patient with FS and GHD who continued rhGH therapy for 5 years. The
differential diagnosis of GHD should also be considered for FS patients with
short stature.
PMID- 28509132
TI - Transient Fanconi syndrome in two preterm infants with hydronephrosis and urinary
tract infection.
AB - Type IV renal tubular acidosis is known to occur in obstructive uropathy with
urinary tract infection. Fanconi syndrome, however, has not been described in
these settings. We report two preterm infants who developed Fanconi syndrome
associated with hydronephrosis and urinary tract infection. Patient 1 is a boy
with 21 trisomy, bilateral renal hypoplasia and bilateral vesicoureteral reflux
delivered at 35 weeks' gestation. At postnatal day 42, he developed Fanconi
syndrome after urinary tract infection, which persisted until the surgical
correction of vesicoureteral reflux. Patient 2 was delivered at 35 weeks'
gestation. At postnatal day 9, he was admitted for severe dehydration. He had
phimosis and ultrasonography showed left pelviectasis. Laboratory data were
compatible with Fanconi syndrome, which resolved spontaneously after fluid
therapy. Subsequently urine culture grew bacteria and treatment for infection and
topical corticosteroid for phimosis were performed. DMSA scintigraphy performed
later showed left renal scar. Tubular cell stretch, due to vesicoureteral reflux
in Patient 1 and phimosis in Patient 2, and urinary tract infection in
association with immaturity of tubules are thought to have caused Fanconi
syndrome.
PMID- 28509133
TI - Denosumab for treatment of immobilization-related hypercalcemia in a patient with
end-stage renal disease.
AB - The efficacy and safety of denosumab for the treatment of immobilization-related
hypercalcemia in end-stage renal disease remain uncertain. We describe the case
of a hemodialysis patient with immobilization-related hypercalcemia who was
successfully treated with denosumab. A 79-year-old man admitted for hemodialysis
after sustaining an acute kidney injury developed immobilization-related
hypercalcemia due to the impairment resulting from an acute myocardial
infarction, acute heart failure, and catheter-related bloodstream infection.
After admission, the patient's corrected serum calcium rose to 12.9 from 8.8
mg/dL. A bisphosphonate (alendronate) was administered, but it was ineffective.
Subsequently, treatment with denosumab proved to be effective and his corrected
serum calcium level declined to 9.3 mg/dL within 1 week. Hypocalcemia, which is
an adverse effect of denosumab, was prevented using active vitamin D and calcium
supplementation, and his calcium level stabilized. Thus, our case demonstrates
that denosumab is a viable therapeutic option for dialysis patients experiencing
immobilization-related hypercalcemia.
PMID- 28509134
TI - Two cases of atypical hemolytic uremic syndrome (aHUS) and eosinophilic
granulomatosis with polyangiitis (EGPA): a possible relationship.
AB - Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by
hemolysis, thrombocytopenia, and renal failure. It is related to genetic
mutations of the alternative complement pathway and is difficult to differentiate
from other prothrombotic microangiopathies. Eosinophilic granulomatosis with
polyangiitis (EGPA) (Churg-Strauss syndrome, CSS) is a systemic ANCA-associated
vasculitis and a hypereosinophilic disorder where eosinophils seem to induce cell
apoptosis and necrosis and therefore, vasculitis. Here, we report the case of two
CSS patients with a genetic complement disorder consistent with aHUS diagnosis.
Both patients showed histologic features that supported the diagnosis of CSS, and
a genetic complement study confirmed the suspected aHUS diagnosis. In the case
where eculizumab was administered, the global response was excellent. There is
very limited understanding of the genetics and epidemiology of both, atypical HUS
and EGPA, but considering our two patients we suggest that an etiopathogenic link
exists among patients diagnosed with both entities.
PMID- 28509135
TI - Renal-limited vasculitis with elevated levels of multiple antibodies.
AB - Renal-limited vasculitis (RLV) is a type of anti-neutrophil cytoplasmic antibody
(ANCA)-associated vasculitis that presents with crescentic glomerulonephritis
with no other organ involvement. Although several studies reported patients with
crescentic glomerulonephritis who were dual positive for proteinase 3 (PR3)-ANCA
and myeloperoxidase (MPO)-ANCA or ANCA and anti-glomerular basement membrane
(GBM) antibody, patients positive for all three antibodies, i.e., triple-positive
patients, were rarely reported. We herein report the case of a male with pauci
immune type crescentic glomerulonephritis positive for MPO-ANCA, PR3-ANCA, and
anti-GBM antibody. Renal biopsy led to the definitive diagnosis of RLV with pauci
immune-type crescentic glomerulonephritis. Fluorescence immunostaining showed no
linear deposition of IgG on GBM, indicating no involvement of anti-GBM associated
diseases. Intensive therapy, including prednisolone, plasma exchange, and
intravenous cyclophosphamide, was effective. We report the case of triple
positive patient with crescentic glomerulonephritis, who was successfully treated
with glucocorticoid, plasma exchange, and cyclophosphamide, suggesting that
treatment for RLV in the patient with serological triple antibodies positivity in
the absence of linear IgG deposition could benefit from the combination therapy
regimen for plasma exchange and primary induction of remission against
microscopic polyangiitis.
PMID- 28509136
TI - Primary hepatic leiomyosarcoma in a patient with autosomal dominant polycystic
kidney disease.
AB - Primary hepatic leiomyosarcoma is an extremely rare tumor. The diagnosis is
difficult, and its etiologic factors have not been clarified. A 63-year-old woman
with numerous cysts in her kidneys and liver was diagnosed with autosomal
dominant polycystic kidney disease (ADPKD). Several members of her family also
had ADPKD. She underwent treatment with tolvaptan to inhibit cyst growth and slow
the decline in kidney function. Eight months after the start of the therapy, she
was hospitalized with fatigue and fever of unknown origin. Diagnostic imaging
showed a very large hepatic tumor, and histologic examination of a fine-needle
biopsy specimen revealed the tumor to be malignant. Differentiation between
carcinoma and sarcoma was difficult based on the histological findings. The tumor
was thought to be excisable; therefore, hepatic resection was attempted. At the
time of surgery, as the tumor had grown larger than when imaged, complete
resection was impossible. However, a part of the tumor was resected.
Histopathological and immunohistological examinations of the surgical specimen
confirmed a primary hepatic leiomyosarcoma. Whether the tumor was associated with
the presence of ADPKD remains unclear, however, this is the first report of the
combination of these two diseases in a patient.
PMID- 28509137
TI - Successful treatment by tocilizumab without steroid in a very severe case of
TAFRO syndrome.
AB - Successful use of tocilizumab (TCZ) to treat TAFRO syndrome has recently been
reported. In those cases, TCZ was used with steroid. We present herein the case
of a 59-year-old man with very severe TAFRO syndrome who was successfully treated
using TCZ without steroid. He showed rapidly progressive anasarca, acute renal
failure and very severe thrombocytopenia. We initially used steroid, but its
efficacy was limited. Moreover, steroid use had to be stopped as soon as
possible, because hemorrhagic shock developed due to severe duodenal ulcer. After
overcoming infections (about 40 days after stopping steroid), administration of
TCZ was started and the patient was discharged in clinical remission.
PMID- 28509138
TI - Juvenile nephronophthisis and dysthyroidism: a rare association.
AB - Nephronophthisis, an autosomal recessive kidney disease, represents the most
frequent genetic cause of end-stage kidney disease in the first three decades of
life. A 27-year-old male was presented with gait imbalance, sever pruritus since
10 days prior time of admission. In past medical history, he had bilateral
cataract, torsional nystagmus, and bilateral optic nerve atrophy since 2 years of
age. He was also mentioned history of multinodular goiter with dysfunctional
thyroid state since 2 years before admission. At admission bilateral blindness,
torsional nystagmus, asymmetric thyromegaly with nodularity was found in physical
examination. Laboratory tests showed elevated urea and creatinine (200, 10.7
mg/dl), hypomagnesemia (1.1 mEq/l), decreased thyroid stimulating hormone (<0.004
mIU/l). Ophthalmologist consultation confirmed retinitis pigmentosa. Renal
sonography showed small-sized kidneys. Brain magnetic resonance imaging did not
reveal molar tooth sign. Genetic testing performed and a large homozygous
deletion at the NPHP1 gene locus was found. The patient was diagnosed with
juvenile nephronophthisis and consideration of dysthyroidism as extrarenal
manifestation of nephronophthisis is suggested in this case. Furthermore, loss of
function mutation in SLC41A1 gene that leads to magnesium depletion must be noted
in patients with suspected to nephronophthisis.
PMID- 28509139
TI - Unusual Listeria monocytogenes peritonitis in peritoneal dialysis patient with
liver cirrhosis: a case report and review of literature.
AB - Spontaneous Listeria peritonitis is well described in liver failure, but is
uncommon in peritoneal dialysis patients. Atypical cases where peritonitis
symptoms develop after systemic manifestations are rare and challenging for
diagnostic. A 57-year-old peritoneal dialysis patient with history of ethylic
cirrhosis was admitted after epileptic seizure. On admission, patient was
soporous without signs of peritonitis and meningitis. Patient's peritoneal
effluent was clear, with normal leukocytes. Cranial CT scan showed no
abnormalities. Laboratory exams revealed positive inflammatory syndrome. Despite
antibiotic therapy, next day, symptoms aggravated with coma development.
Peritoneal effluent became cloudy and its leukocyte count rose up. Effluent
microscopy revealed Gram-positive bacilli. Patient was started with
intraperitoneal Vancomycin and Amikacin. Patient's clinical condition
deteriorated with lethal outcome. Post-mortem analysis of effluent and blood
culture showed growth of L. monocytogenes. Apart from idiopathic etiology, goat
milk curd, that patient had started consuming 10 days before admission, could
theoretically be considered as possible infection vehicle. L. monocytogenes
peritonitis in peritoneal dialysis patients is rare, but must be considered in
immunocompromised or patients with concomitant liver failure, especially after
Gram-positive bacilli identification in peritoneal effluent. In case of
suspiscion of Listeria peritonitis, Ampicillin should be initiated, because
bacteria often poorly respond to currently recommended empiric regimens.
PMID- 28509140
TI - A rare adult case of poststreptococcal acute glomerulonephritis with a
retropharyngeal abscess.
AB - Retropharyngeal abscess is an infection involving the retropharyngeal space which
is posterior to the pharynx and oesophagus, and it results as a complication of a
primary infection elsewhere in the head and neck including the nasopharynx,
paranasal sinuses, or middle ear, which drain lymph to the retropharyngeal lymph
nodes. Their lymph nodes are prominent in children and atrophy with age.
Therefore, retropharyngeal abscess is most frequently encountered in children,
with 75% of cases occurring before the age of 5 years, and often in the first
year of life. We experienced a rare adult case of poststreptococcal acute
glomerulonephritis with a retropharyngeal abscess, and conservative therapy
ameliorated them. According to past reports, only one child with a
retropharyngeal abscess and poststreptococcal acute glomerulonephritis has been
presented at a conference to date; this is the first adult case of
poststreptococcal acute glomerulonephritis with a retropharyngeal abscess.
Retropharyngeal abscess can be fatal including airway compression, so it is
important to remember retropharyngeal abscess in a case of poststreptococcal
acute glomerulonephritis with severe symptoms of neck.
PMID- 28509141
TI - Primary Ewing sarcoma of the kidney: a case report and treatment review.
AB - Ewing sarcomas/primitive neuroectodermal tumors (ES/PNET) of the kidney are
rarely found high-grade malignant tumors, offering poor prognosis. Although
established treatment guidelines for ES of kidney are scarce, a multi-modality
treatment approached is typically implemented. Herein, we report a 14-year-old
female patient with ES of right kidney. Post-nephrectomy disease recurrence was
treated with chemotherapy (i.e., vincristine, doxorubicin and cyclophosphamide);
marked reduction in tumor size (i.e., from 18.5 * 11.3 cm2 to 3.7 * 2.2 cm2; ~96%
reduction in size) as per computed tomography images was observed. We present our
treatment experience and review from the available literature.
PMID- 28509142
TI - Erosion of a Tenckhoff catheter to the sigmoid colon: an uncommon delayed
complication.
AB - Continuous ambulatory peritoneal dialysis is one of the most commonly used
therapies for patients with impaired renal function. Most frequent complications
directly related to the catheter usually present within the first weeks, and
range from catheter dysfunction to dialysis-associated peritonitis; bowel
perforation while placing the catheter is uncommon, and it is usually assessed in
the same surgical event. There are, however, delayed complications, and one of
the least frequently described is erosion of the catheter into the bowel. We
present the case of a 65-year-old man, who shows up at the emergency room
referring to "acute diarrhea" associated with his dialysis, it is quickly
diagnosed as a bowel perforation and underwent emergency surgery. During the
operation we found adhesions compromising small bowel and sigmoid colon, the far
end of the dialysis catheter inside the sigmoid colon, with no signs of colonic
leakage to the peritoneal space. We removed the dialysis catheter, resected the
fibrous borders of the site of insertion and performed a primary closure. The
patient evolved satisfactorily and was subsequently discharged to continue with
hemodialysis for renal substitution therapy.
PMID- 28509143
TI - Anaphylactoid reaction to immunoadsorptive membrane in a patient with myasthenia
gravis.
AB - Extracorporeal adsorption therapy has been carried out clinically in cases of
myasthenia gravis (MG) since the 1980s without any major complications. Despite a
lack of clinical evidence, it has been accepted as a potential therapy for
steroid-resistant patients in many institutes. Recently, we experienced a case of
MG with an anaphylactoid reaction during extracorporeal immunoadsorption therapy.
A 64 year old women with MG showed an anaphylactoid reaction immediately after
the initiation of adsorption therapy using a polyvinylalcohol gel column. It is
therefore important to bear in mind that extracorporeal adsorption therapy could
trigger an anaphylactoid reaction, which may induce a MG crisis.
PMID- 28509144
TI - A case of familial Mediterranean fever-associated systemic amyloidosis.
AB - Familial Mediterranean fever (FMF) is a chronic inflammatory disease,
characterized by recurrent fever and polyserositis (pleuritis and/or
peritonitis). The most important complication of FMF is amyloidosis, which causes
chronic renal failure. Colchicine is the most effective treatment in acute
attacks and amyloidosis development. However, the majority of patients with
amyloidosis have a relentless progression to end-stage renal disease despite
initiation of colchicine treatment. We present the case of a 38-year-old man with
FMF-associated chronic renal failure due to systemic amyloidosis. The patient
suffered from periodic fever and renal insufficiency, and was admitted to our
hospital. Laboratory examination revealed an inflammatory reaction, renal
dysfunction (serum creatinine 2.5 mg/dl), and proteinuria. Renal biopsy revealed
segmental mesangial AA amyloid deposits in several glomeruli and the walls of
several vessels. Genetic analysis showed that the patient was heterozygous for
the MEFV gene (E148Q/M694I). Thus, he was diagnosed with FMF, and colchicine
treatment was initiated. He remained almost attack free, with decreasing serum
creatinine levels (1.6 mg/dl) and diminishing urinary protein excretion. In
conclusion, renal amyloidosis is the most important long-term complication of
FMF, and treatment with colchicine is effective for preventing progression.
Therefore, colchicine treatment should be initiated as early as possible after
the diagnosis of FMF.
PMID- 28509145
TI - Gastric bleeding reduced upon switch from haemodialysis to CAPD.
PMID- 28509146
TI - Efficacy of tocilizumab, a humanized neutralizing antibody against interleukin-6
receptor, in progressive renal injury associated with Castleman's disease.
AB - Castleman's disease is a benign lymphoproliferative disorder in which interleukin
6 (IL-6), a pleiotropic proinflammatory cytokine, is thought to play a
pathogenetic role. Presented is the case of a 72-year-old man with Castleman's
disease who exhibited progressive renal dysfunction with proteinuria. Renal
biopsy revealed mesangial hypercellularity and matrix expansion in most glomeruli
and peritubular inflammatory cell infiltration. Immunofluorescence studies showed
intense deposition of IgG in a granular pattern along the glomerular basement
membrane. Histological features were compatible with membranoproliferative
glomerulonephritis accompanied by interstitial inflammatory cell infiltration.
Immunohistological analysis showed that IL-6 was abundantly expressed by tubular
cells and interstitial macrophages, suggesting involvement of IL-6 in the renal
injury. As a result of administration of tocilizumab, a humanized anti-IL-6
receptor antibody, the patient experienced clinical and biochemical improvement
of Castleman's disease, including marked reduction of proteinuria and
stabilization of renal function. These findings suggest the efficacy of
tocilizumab against Castleman's disease and its renal complications.
PMID- 28509147
TI - Granulomatous interstitial nephritis in a renal allograft.
AB - We describe a middle-aged woman in whom granulomatous interstitial nephritis
(GIN) developed in a renal allograft. She had undergone bowel resection due to an
uncertain diagnosis of active granulomatous bowel disease 30 years earlier.
Thereafter, frequent hyperoxaluria as well as calcium oxalate stone and recurrent
urinary tract infections had resulted in a progressive deterioration in kidney
function over a period of 20 years. She underwent living donor kidney
transplantation; however, her kidney function progressively deteriorated, despite
transplantation. A biopsy of the renal allograft revealed GIN with granulomatous
vasculitis accompanied by calcium oxalate crystals. These as well as the
laboratory findings indicated a diagnosis of sarcoidosis. We considered that the
aggravated granulomatous inflammation on the allograft was caused by recurrent
sarcoidosis accompanied by hyperoxaluria.
PMID- 28509148
TI - Lupus-like glomerulonephritis: an autoimmune complication of hepatitis C
infection.
AB - Lupus-like glomerulnephritis in patients with negative lupus serologies and no
extra-renal manifestations of lupus can create a diagnostic dilemma. We describe
a 53-year-old gentleman with chronic hepatitis C virus (HCV) infection who
presented with dialysis-requiring renal failure, renal histologic findings of
"full-house" immunofluorescence label and tubuloreticular inclusions on
electronic microscopy, but no extra-renal or laboratory signs of systemic lupus
erythematosis. Attempted treatment with cyclophosphamide and corticosteroids was
limited by cyclophosphamide hypersensitivity. The patient remained dialysis
dependent over 18 months of observation and did not develop extra-renal clinical
or biological manifestations of lupus. Mimics of seronegative lupus with isolated
renal involvement can include HCV-related autoimmunity. Treatment of acute
glomerulonephritis may be similar initially, but other concerns in patients with
HCV infection include excluding cryoglobulinemia, the potential impact of
immunosuppression therapy on liver disease and consideration of subsequent use of
antiviral therapy. Given the increasing prevalence of HCV globally, the
recognition of extra-hepatic autoimmune manifestations of HCV infection will
likely increase.
PMID- 28509149
TI - A case of renal hypouricemia and a G774A gene mutation causing acute renal injury
that was improved by hemodialysis.
AB - A 16-year-old man came to our hospital complaining of loin pain after a middle
distance race. Following admission, his renal dysfunction worsened rapidly,
requiring several hemodialysis sessions. A renal biopsy showed no change in the
glomeruli, although interstitial edema was observed. Following the recovery of
renal function, we confirmed that his uric acid level was abnormally low and
urate clearance was abnormality high. Gene analysis showed that he had a G774A
mutation which dominated the SLC22A12 gene encoding the urate transporter 1.
PMID- 28509150
TI - Primary omental pleomorphic liposarcoma identified at autopsy in a living donor
kidney transplant recipient.
AB - Metastatic and recurrent tumors of the omentum are common, but primary omental
pleomorphic liposarcoma (POPL) is an extremely rare type of solid omental tumor.
We describe the case of a patient with POPL who received a renal transplant from
a living donor. Despite good allograft function, the volume of peritoneal fluid
gradually increased. An exploratory laparotomy could not be performed because the
patient was obese and developed hemodynamic instability. Therefore, a shunt was
placed between the peritoneal cavity and the internal jugular vein using the
Denver(r) shunt system; however, the patient died of respiratory insufficiency.
On the basis of the autopsy results, we diagnosed the patient's condition as
POPL. We speculated that the malignancy did not originate directly from the donor
cells. We report POPL in a living donor renal transplant recipient.
PMID- 28509151
TI - Two cases of atypical membranoproliferative glomerulonephritis showing opposite
clinical course.
AB - Atypical membranoproliferative glomerulonephritis (MPGN) is considered to
progress to typical MPGN, and it is believed that it can be treated with
corticosteroids. However, consensus that atypical MPGN is a continuum of
morphologic manifestations of typical MPGN cannot be reached. Herein, we report
two cases of atypical MPGN with opposite clinical course. Case 1 was a 4-year-old
boy with macrohematuria and proteinuria with no prodromal symptoms. His serum C3
level had abruptly dropped, and renal biopsy confirmed a diagnosis of atypical
MPGN. After performing kidney biopsy, his urinary abnormality improved and his C3
level had normalized 1 year after onset without medication. At the most recent
follow-up, neither proteinuria nor hematuria was detected. Case 2 was a 7-year
old girl with microhematuria and proteinuria at her school urinary screening. Her
first biopsy finding was similar to dense deposit disease, and the second biopsy
showed atypical MPGN. Oral corticosteroids were started from this point, but
heavy proteinuria and hypocomplementemia could not be improved sufficiently. We
immediately performed third kidney biopsy and diagnosed typical MPGN. These
findings suggest that the indication of therapy for atypical MPGN should be re
examined. Aggressive therapy such as steroid administration is not necessarily
essential and effective for therapeutic intervention of all atypical MPGN.
Moreover, atypical MPGN may involve different etiologic and pathogenetic factors,
rather than a continuum of morphologic manifestations of MPGN.
PMID- 28509152
TI - Kidney transplantation during a twin pregnancy. Case report and review of the
literature.
AB - Kidney transplant in a pregnant woman is exceptional, with only six cases being
reported. Pregnancy was not known at the time of the transplant in five of these
cases. We report the case of a 26-year-old woman who was diagnosed as carrying a
twin pregnancy 4 months after starting hemodialysis. In order to improve the
survival chances for the twins, she underwent an orthotopic renal transplant from
a living donor at 20 weeks of gestation. The allograft functioned immediately and
4 weeks passed without incident. At the 26th week of gestation, the patient had a
precipitous labor, delivering two male babies with no malformations, weighing 755
and 890 g, who died due to respiratory failure. The allograft worked normally
afterwards. Sixteen months later, the patient delivered a normal 37 weeks'
gestation baby. The renal graft continued working normally for the next 20 years,
after which signs of chronic allograft nephropathy developed. Azathioprine was
replaced with mycophenolate mofetil. At the last evaluation, 23 years after
transplant, the patient's serum creatinine was 2.9 mg/dl and her estimated
glomerular filtration rate (eGFR) was 22 ml/min/1.73 m2. This unique case
demonstrates that it is possible to perform an orthotopic kidney transplant in a
20-week twin-gestation, with a long graft survival time.
PMID- 28509153
TI - Morphological analysis of biofilm of peritoneal dialysis catheter in refractory
peritonitis patient.
AB - A 66-year-old man undergoing peritoneal dialysis (PD) was admitted to our
hospital for treatment of PD-related peritonitis. Culture of the PD fluid
revealed the presence of Citrobacter freundii, and therapy with ceftazidime was
started intraperitoneally. The cell count in PD fluid slowly decreased over time
during the first 2 weeks of treatment, but increased again on the 14th hospital
day. A second culture of the PD fluid revealed the presence of Enterococcus
species. A switch in antibiotic therapy to vancomycin did not improve the cell
count in the PD fluid. A third culture of the PD fluid revealed the presence of
Stenotrophomonas maltophilia. The PD was discontinued and the catheter removed on
the 28th hospital day. Examination of the catheter revealed that the inner tip
was coated with a fibrous sheet of cells, suggesting biofilm formation. Following
catheter removal, the patient was administered intravenous ciprofloxacin, and the
inflammatory reaction started to disappear immediately and had completely
disappeared after 1 week of treatment. Microscopic analysis of the fibrous
structure on the catheter revealed multiple layers of various inflammatory cells.
Immunostaining revealed the presence of CD44-positive polynuclear cells,
indicating neutrophils, facing the catheter lumen. CD68-positive cells,
indicating macrophages, were observed in the following layer, and keratin
positive cells, indicating peritoneal mesothelial cells, were present at the
bottom of the structure. Based on the immediate improvement of PD-related
peritonitis after catheter removal, we presumed that this biofilm contributed to
the intractability of the patient's peritonitis. Morphological analysis of
catheter revealed that both the mesothelial cells and the various inflammatory
cells may have contributed to biofilm development.
PMID- 28509154
TI - Successful treatment of icodextrin-single peritoneal dialysis for refractory
nephrotic syndrome induced by idiopathic membranous nephropathy.
AB - The patient was a 76-year-old male who developed nephrotic syndrome. Idiopathic
membranous nephropathy was diagnosed by renal biopsy and clinical findings. The
patient had been refractory to predonisolone and cyclosporine A therapies, and
overhydration recurred repeatedly during the clinical course. One year after an
initial hospitalization, he had to be hospitalized a second time because of
overhydration. During the hospitalization, he underwent fluid removal by the
extracorporeal ultrafiltration method (ECUM), as his response to diuretics was
too weak to permit the control of cardiac insufficiency. The ECUM alleviated his
overhydration, but no remission of nephrotic syndrome was achieved. The patient
was then discharged temporarily, but overhydration developed again 2 months
later. Peritoneal dialysis (PD) using an overnight dwell of a single dose of
icodextrin was initiated to obtain stable fluid removal. This promptly alleviated
the refractory subcutaneous edema, and type I incomplete remission of nephrotic
syndrome was achieved about 2 weeks after the start of PD. The patient could be
withdrawn from the PD therapy 4 months later. Subsequently, the urinary volume
was maintained and the serum creatinine level was stabilized at about 2 mg/dl. In
our patient, the protein leakage into the drainage was small enough to permit
remission of the nephrotic syndrome with stable fluid removal. On this basis, we
believe that PD using icodextrin is considered as one of the options for the
treatment of refractory nephrotic syndrome with poor water control.
PMID- 28509155
TI - Interaction of miconazole oral gel with warfarin and cyclosporine in a patient
with nephrotic syndrome.
AB - It is well known that miconazole inhibits cytochrome P450 (CYP). However, this
drug in oral gel form is believed not to absorb into systemic circulation, and
therefore not to inhibit CYP. We experienced a case of increased oral
bioavailability of warfarin and cyclosporine with this gel for treatment of oral
candidiasis in a patient with nephrotic syndrome. Her prothrombin time
international normalized ratio (PT-INR) increased from 2 to 7.25, and the
cyclosporine concentration at 2 h after final dosing (C2) increased from 633.8 to
1396.5 ng/ml 6 days after the coadministration. These problems were resolved by
termination of the gel and switching to amphotericin B gargle. We further
detected a significant amount of miconazole in her plasma, directly showing for
the first time in a patient with this interaction that oral miconazole gel was
actually absorbed into systemic circulation. Because warfarin and cyclosporine
are often used simultaneously by nephrologists, caution should be applied with
combined use of these drugs and oral miconazole gel to avoid adverse reaction.
PMID- 28509156
TI - BK virus-induced acute motor-axonal polyneuropathy in a renal transplant patient.
AB - Neurological complications are not uncommon in patients with renal
transplantation, mostly affecting the central nervous system, and less frequently
the peripheral nerves. BK virus infection is relatively common in transplant
recipients and in some cases may lead to neurological complications. In this
report, we present an interesting case of a patient who developed acute axonal
motor polyneuropathy in the course of BK virus infection 3 months after kidney
transplantation. After BK virus clearence in blood, a significant improvement was
noted in her polyneuropathy. In patients with acute axonal motor polyneuropathy
after transplantation BK virus-induced polyneuropathy should be excluded.
PMID- 28509157
TI - Extrapulmonary tuberculosis presented as fever of unknown origin in two patients
with endstage kidney disease not on dialysis: usefulness of 18-FDG-PET/CT in the
diagnostic localization of fever of unknown origin.
AB - Tuberculosis is one of the common causes of fever of unknown origin in patients
with chronic kidney disease (CKD). Extrapulmonary tuberculosis is more common in
CKD patients, and is, unfortunately, often underdiagnosed despite extensive
assessments. Recently, fluorine-18-deoxyglucose-positron emission
tomography/computed tomography (FDG-PET/CT) has been available in the diagnosis
of malignancy, inflammatory and infectious diseases, and has become a useful
diagnostic tool. Here, we present two cases of endstage kidney disease who
presented with fever of unknown origin at the time of dialysis initiation. In
both cases, although interferon-gamma-releasing assay was positive, combined
conventional diagnostic modalities such as computed tomography and gallium
citrate scintigraphy failed to detect the sites infected with tuberculosis. By
contrast, extrapulmonary lesions were detected by FDG-PET/CT and successfully
treated with combined anti-tuberculous drugs. Diagnosis of extrapulmonary
tuberculosis was confirmed by biopsy of the affected lymph node and lumbar spine,
followed by PCR of the biopsied specimen. These cases highlight the importance of
considering tuberculosis as one of the differential diagnoses in pre-dialysis CKD
patients with persistent fever, and the usefulness of FDG-PET/CT in the detection
of infectious sites of extrapulmonary tuberculosis.
PMID- 28509158
TI - Treatment of a recurrent renal artery stenosis and stent fracture using a drug
eluting stent in a pediatric patient.
AB - Renal artery obstruction is uncommon in the pediatric population and therefore
represents a challenging diagnosis to ascertain and treat. While angioplasty and
surgery have been used to treat it, stent implantation has been left mainly for
adult use. In the following paper, we expose the case of an 8-year-old female who
presented with severe arterial hypertension. Initially, the patient was evaluated
and up to 5 antihypertensive medications were started. After complete evaluation,
she was found to have severe right renal artery distal and proximal stenosis. She
underwent recurrent angioplasties and then a bare metal stent (BMS) implantation,
due to recurrence of stenosis. The original BMS developed a circumferential
fracture, leading to a second stent implant, this time using a drug eluting stent
(DES). She has been stable for 8 years since the last intervention, although
using 2 antihypertensive medications. The use of BMS and DES may add another tool
in the armamentarium of the pediatric interventionist to treat these children
with recurrent stenosis that fail angioplasty.
PMID- 28509159
TI - Autoimmune autonomic ganglionopathy manifesting as acute-onset orthostatic
hypotension in a patient undergoing peritoneal dialysis.
AB - Orthostatic hypotension is an important complication in the management of
patients receiving dialysis therapy. As for the orthostatic hypotension caused by
decreased peripheral artery resistance, diabetic neuropathy and amyloidosis are
the two main causes of hypotension in dialysis patients. However, some patients
develop orthostatic hypotension that is caused by dysfunction of the autonomic
nervous system, not by diabetic or amyloidosis-related neuropathy. We herein
present a case of a 56-year-old man with a 17-year history of peritoneal dialysis
therapy, who developed acute-onset orthostatic hypotension accompanied by
hypohidrosis and erectile dysfunction. Because serum autoantibodies to ganglionic
nicotinic acetylcholine receptor were detected, he was diagnosed with autoimmune
autonomic ganglionopathy (AAG). He was treated with high-dose immunoglobulin
therapy (0.6 g per kg of body weight per day) for 5 consecutive days, which
resulted in a gradual improvement in dizziness. Two months after the onset of
AAG, he could discontinue vasopressors (fludrocortisone acetate and midodrine
hydrochloride) and continued maintenance dialysis therapy without the use of
vasopressors. This case indicates that physicians should consider autonomic
neuropathy including AAG as a differential diagnosis when they encounter dialysis
patients with orthostatic hypotension.
PMID- 28509160
TI - Hypersensitivity reactions to acetate in the bicarbonate dialysate in a patient
undergoing pre-dilution online hemodiafiltration.
AB - A 63-year-old male patient first experienced recurrent hypotensive episode during
the dialysis session just after switching the mode from hemodialysis to online
hemodiafiltration (OL-HDF) with infusion in pre-dilution of the bicarbonate
dialysate containing 9.2 mEq/L of acetate. Peripheral eosinophil count and serum
IgE were both elevated to 16,440/MUL and 2000 IU/L. The reactions promptly
dissolved with substitution of acetate-free solution. This case illustrated that
pre-dilution OL-HDF can induce an occult hypersensitivity to acetate in the
standard bicarbonate dialysate.
PMID- 28509161
TI - Use of LightCycler mutation analysis to detect type II adenine
phosphoribosyltransferase deficiency in two patients with 2,8
dihydroxyadeninuria.
AB - Recently, a number of methods have been devised for detection of mutations in the
field of molecular genetics. The LightCycler system has been used for rapid PCR,
while simultaneously quantifying and analyzing the amplification results. We
tried to apply the LightCycler system to detect APRT*J allele mutations in two
families including two children with 2,8-dihydroxyadenine urolithiasis. The first
patient was a 3-year-old girl who presented with left flank pain. The second
patient was a 2-year-old girl who presented with complaints of sudden dysuria.
The spectrophotometric analysis of the stone fragments of both patients revealed
an absorption spectrum for 2,8-DHA. We used the LightCycler system to detect
APRT*J mutation. The first patient was homozygous for APRT*J/APRT*J and the
second patient was compound heterozygous for APRT*J/APRT*Q0. The genetic
diagnosis of APRT deficiency using this system may be useful not only as a
diagnostic test for infants with known 2,8-DHA, but also as a screening of
infants with a suspicion of urolithiasis. We believed that the LightCycler system
still is an important means of identifying APRT*J mutation.
PMID- 28509162
TI - A case of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO)
syndrome complicated by IgA nephropathy with nephrotic syndrome.
AB - A 62-year-old man visited our hospital with a mild sore throat, high-grade fever,
and clavicular pain. Seven years earlier, he had been diagnosed with synovitis,
acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. His clavicles were
tender and remarkably swollen. Also noted was marked pitting edema in the lower
extremities and pustulosis on the palms and soles of the feet. Laboratory studies
on admission showed an elevated white cell count (23,400/MUl) and serum C
reactive protein level (24.4 mg/dl). Urinalysis revealed proteinuria (2+) and
occult blood (3+) with numerous dysmorphic red blood cells and hyalin casts. The
patient was diagnosed with recurrence of his SAPHO syndrome and started on oral
glucocorticoid therapy. By day 9 after admission, he had gained 16 kg in body
weight, and his proteinuria (6.4 g/day) and serum creatinine level (2.3 mg/dl)
were elevated. Renal biopsy revealed mesangial proliferative glomerulonephritis
with deposition of IgA and C3 in the mesangial area and along the capillary
walls. The patient was diagnosed with IgA nephropathy accompanied by nephrotic
syndrome. With oral prednisolone therapy, his fever, clavicular pain, and
proteinuria were gradually relieved. The clinical course in this case suggests
the onset of nephrotic syndrome with IgA nephropathy was associated with the
recurrence of the patient's SAPHO. To our knowledge, this is the first reported
case of SAPHO-associated IgA nephropathy.
PMID- 28509163
TI - Hypokalemia-associated paralysis and metabolic acidosis in a patient with
bilateral ureterosigmoidostomy.
AB - Ureterosigmoidostomy is a urological intervention performed to treat various
conditions such as invasive bladder cancer, bladder exstrophy, vesicovaginal
fistula, or urethral trauma. However, this intervention may lead to several
metabolic complications. Here, we report an interesting case with quadriparesis
and intestinal paralysis resulting from severe hypokalemia (the serum potassium
level, 1.8 mEq/L) and hyperchloremic metabolic acidosis [pH 6.927 and the
arterial bicarbonate level, 8.0 mEq/L] in a 65-year-old man who had undergone
bilateral ureterosigmoidostomy for bladder cancer 16 years earlier. The abdominal
computed tomography scan also showed that massive fluid consisting of the mixture
of the diverted urinary stream and feces was accumulated in the dilated distal
colon. The treatment with intravenous potassium and sodium bicarbonate
administration combined with the drainage of the diverted urinary stream from the
distal colon resulted in the restoration of hypokalemia and acidosis followed by
the improvement of quadriparesis and intestinal paralysis. The underlying
mechanism and the treatment of metabolic complications after ureterosigmoidostomy
are briefly discussed.
PMID- 28509164
TI - Familial Mediterranean Fever developing in a Japanese kidney transplant
recipient.
AB - Familial Mediterranean Fever (FMF) is an auto-inflammatory disease characterized
by periodic febrile episodes and sterile polyserositis and is extremely rare in
Asian populations. Here, we report a case of FMF in a 61-year-old Japanese man
who received a kidney transplant 31 years ago but had to re-start hemodialysis.
Although kidney function had been stable since his initial transplant, serum
creatinine levels had been increasing over the 2 years prior to his presentation
at our hospital, and a periodic fever developed at the same time. Uremic symptoms
were observed, and hemodialysis was re-started, prompting the patient to choose
to undergo a second kidney transplantation. We re-checked his medical history and
conducted further physical examinations. Given that the patient had previously
undergone an operation for olecranon bursitis in which pericardial effusion had
been identified, we considered the possibility of FMF and conducted a genetic
test, which identified the E202Q heterozygous mutation in the MEFV gene. The
patient was therefore diagnosed with variant FMF. To our knowledge, this is the
first report of a Japanese kidney transplant recipient being diagnosed as an FMF
variant. We describe the relationship of FMF and kidney transplantation in terms
of prognosis and important points to note for treatment.
PMID- 28509165
TI - Fraternal twins with job's syndrome and immune complex nephritis.
AB - Job's syndrome or autosomal dominant hyperimmunoglobulin E syndrome (Hyper-IgE)
is a rare disorder that results from a STAT3 gene mutation, which results in the
absence of T-helper 17 (Th17) cells and manifests as a severe immunodeficiency.
Affected individuals suffer recurrent soft tissue and pulmonary infections among
other manifestations, and the spectrum of the disease is still being
characterized. We describe 2 sisters with Job's syndrome each with variable
expressivity. However, both patients developed proteinuric kidney disease and had
biopsies confirming the presence of immune complex glomerulonephritis with
staining for immunoglobulins and complement components. Previous reports link
Job's syndrome and the development of systemic lupus erythematosus (SLE), but
proliferative immune complex glomerulonephritis has not been described. We
speculate that continual internal and external antigen exposure may induce an
autoimmune process similar to SLE, which in turn may account for the immune
complex disease in the kidney.
PMID- 28509166
TI - Rhabdomyolysis as the first manifestation of human immunodeficiency virus
infection.
AB - Renal tubular acidosis (RTA) is a known complication of anti-retroviral
medications. The presence of RTA in treatment naive-HIV patients is rare. A 49
year-old Caucasian woman presented with recurrent non-anion gap metabolic
acidosis, AKI, rhabdomyolysis and hypokalemia on several occasions. Diagnosis of
acquired distal RTA due to HIV was made given the history and laboratory data. To
the best of our knowledge, this is the first case of HIV diagnosed with an
initial presentation of rhabdomyolysis. We believe that acute renal failure was
due to hypokalemia precipitating rhabdomyolysis caused by HIV-induced dRTA which
was further exacerbated by amphetamine use.
PMID- 28509167
TI - An autopsy case of vertebrobasilar dolichoectasia under hemodialysis due to
autosomal dominant polycystic kidney disease.
AB - A 60-year-old male with end-stage kidney disease due to autosomal polycystic
kidney disease began maintenance hemodialysis in 2005. A brain CT scan showed
dilatation of left vertebral artery, basilar artery, bilateral post cerebral
artery, and middle cerebral artery. At the time, he was diagnosed as
vertebrobasilar dolichoectasia. He was once admitted to our hospital for ischemic
stroke. After discharge, he was treated with anticoagulant agent from 2010 to
2012 without any new stroke events. In March, 2012, he was admitted to our
hospital for an evaluation of diplopia and left hemiplegia. Brain MRI showed
acute ischemia of bilateral pons and right temporal lobe. He was once recovered
with urokinase and argatroban, but 3 months after admission, he died with sudden
hypotension and impaired consciousness. Autopsy revealed that subarachnoid
hemorrhage due to the rupture of basilar artery aneurysm was responsible for this
event.
PMID- 28509168
TI - Immune thrombocytopenic purpura masking the fatal potential of calciphylaxis in a
haemodialysis patient.
AB - Calciphylaxis on the background of immune thrombocytopenic purpura (ITP) has
never been described. The pathogenesis of calciphylaxis is complex and not fully
understood as yet. ITP has a complex pathogenesis that leads to bleeding or
thrombotic events. Although ITP is treatable and reversible, calciphylaxis on the
other hand, responds poorly to treatment and carries high mortality and
morbidity. We present a case of a 56-year-old lady with end-stage renal disease
with ITP, who complained of 1-month history of painful necrotic patches over the
thighs. Due to delayed diagnosis, the patient deteriorated and passed away
despite aggressive multidisciplinary approach. This case highlights the
importance of early recognition of the increased thrombotic risk in an end-stage
renal failure patient with poor phosphate control and ITP.
PMID- 28509170
TI - Cystinuria in a patient with 19q12q13.1 deletion.
AB - Cystinuria is a genetic cause of kidney stones with a prevalence of 1 in 7000
births. So far, two genes have been described responsible for this disorder
(SLC3A1 and SLC7A9). We report a patient with an SLC7A9 gene mutation located in
19q13.1 on one allele and with a 19q12q13 region deletion on the other allele.
The characteristic clinical features of the 19q13.1 microdeletion syndrome
include facial dysmorphism, signs of ectodermal dysplasia, growth retardation,
neurologic features and genitourinary anomalies. Cystinuria has not yet been
described as part of this syndrome, although one of its responsible genes
(SLC7A9) is in the same genomic location. The index case is a 6-year-old male
presented with distinctive facial features, cutis aplasia of the scalp,
rudimentary teeth, microcephaly, intrauterine and postnatal growth retardation,
psychomotor developmental delay, speech delay, epilepsy, inguinal hernias and
cystinuria. An array-CGH analysis was performed, finding a large deletion of the
19q12q13.11 cytobands, which affects 19 genes. Two of them are involved in the
19q13.11 deletion syndrome and another affected gene is SLC7A9, responsible for
type B cystinuria. Sanger sequencing was performed as well, detecting a
heterozygous mutation of the SLC7A9 gene, located in 19q13.1. As far as we know,
this is the first described case of cystinuria in a patient with SLC7A9 gene
mutation located in 19q13.1 on one allele and with 19q12q13 region deletion on
the other allele. Although this patient can be classified as a type B
heterozygote and, therefore, his renal prognosis is not severe, the occasional
nephrolithiasis found in such patients justifies a close follow-up with regular
testing of urinary cystine excretion. We suggest that the recessive behavior of
this case, explains the clinical features regarding cystinuria. We propose that
in the face of patients affected of a phenotype matchable with 19q13.11 syndrome
and cystinuria, a mutational or sequencing study of the SLC7A9 gene should be
performed to allow an early onset of diagnosis and treatment.
PMID- 28509169
TI - Successful treatment of a hemodialyzed patient with pure red cell aplasia
associated with epoetin beta pegol therapy with cyclosporine.
AB - A 42-year-old man with end-stage renal failure had been receiving hemodialysis
therapy since April 2009. Initially, darbepoetin alfa was administered to treat
his renal anemia. After treatment was switched to epoetin beta pegol, the
patient's hemoglobin levels rapidly decreased. He was diagnosed with pure red
cell aplasia (PRCA) based on the results of a bone marrow examination. Epoetin
beta pegol was strongly suspected to be the cause of the PRCA, and although he
tested negative for anti-epoetin beta pegol antibodies, epoetin beta pegol was
discontinued and cyclosporine therapy was initiated. Thereafter, his hemoglobin
levels increased, and his anemia dramatically improved after 3 months.
PMID- 28509171
TI - Nephrotic syndrome after scorpion sting.
AB - Scorpion venom is a water soluble, antigenic and heterogeneous mixture. The venom
is composed of varying concentration of neurotoxin, cardiotoxin, nephrotoxin,
haemolytic toxin, phosphodiesterase, phospholipases, hyaluronidases,
glycosaminoglycans, histamine, serotonins, and tryptophan and cytokine releasers.
The reported incidence of scorpion sting in India is 0.6 %. Scorpion sting
resulting in acute renal failure has been reported in the past, but not the
nephrotic syndrome. We report a patient of nephrotic syndrome after scorpion
sting. The lacunae in the present knowledge linking scorpion sting venom with
nephrotic syndrome would only be replete with publications of similar reports.
PMID- 28509172
TI - A case of primary adrenal diffuse large B cell lymphoma presenting with severe
hyponatremia.
AB - We herein report a case of primary adrenal lymphoma with severe hyponatremia. The
patient was admitted for an evaluation of severe hyponatremia and an enlarged
bilateral adrenal mass, which were found in a previous examination for causes of
general fatigue and anorexia. Laboratory data, including the serum levels of
sodium (115 mEq/L), osmolality (239 mOsm/kgH2O), ADH (5.8 pg/mL), cortisol (11.6
MUg/dL), free T3 (2.42 pg/mL), urinary Na (117 mEq/L) and urine osmolality (490
mOsm/kgH2O), fulfilled the diagnostic criteria for the syndrome of inappropriate
secretion of ADH (SIADH). An abdominal computed tomography scan revealed a large
bilateral adrenal mass. A biopsy of the enlarged left adrenal mass revealed
diffuse large B cell lymphoma, which was negative for ADH protein. Hydrocortisone
treatment normalized the patient's body temperature and serum sodium
concentration. In this case, hyponatremia developed when both adrenal glands were
involved and was normalized with hydrocortisone. These findings suggest that
adrenal insufficiency was the cause of hyponatremia, although the basal serum
cortisol was normal. The current case suggests that the administration of
hydrocortisone is recommended if suspicious clinical signs or symptoms are found
in severe hyponatremia, even if hyponatremia is associated with a normal serum
cortisol level and fulfills the diagnostic criteria for SIADH.
PMID- 28509173
TI - A case of minimal change nephrotic syndrome with hypothyroidism deterioration.
AB - A 73-year-old woman with Graves' disease underwent total thyroidectomy and was
being treated with levothyroxine. She developed edema in the lower region of both
legs 1 month before hospitalization. She had a high concentration of urine
protein and was hospitalized for further assessment. A urine protein
concentration of 4.4 g/day was observed, and she was diagnosed with minimal
change nephrotic syndrome (MCNS) after kidney biopsy. The patient's thyroid
function had declined, as indicated by a thyroid-stimulating hormone (TSH) level
of 139.0 MUIU/mL and a free thyroxine (fT4) level of 0.66 ng/dL. She was
prescribed 40 mg/day of prednisolone (PSL) and achieved remission. fT4 level
normalized on the 36th hospital day. She was in remission subsequently. However,
MCNS recurred when PSL was tapered to 10 mg/day. When she was rehospitalized,
thyroid function decline was noted once more, with a TSH level of 29.8 MUIU/mL
and an fT4 level of 0.74 ng/dL. Her oral PSL dose was increased to 30 mg/day, but
she did not achieve remission. However, she achieved remission after steroid
pulse therapy. After remission, the thyroid function normalized. During the
course of her treatment, the levothyroxine dose was maintained at 87.5 MUg/day.
Therefore, we predicted that the loss of thyroid hormone in urine due to
nephrotic syndrome may have led to the aggravation of hypothyroidism. We have
reported this case because of its rarity.
PMID- 28509175
TI - List of referees.
PMID- 28509174
TI - De novo papillary carcinoma in a renal allograft: the pros and cons of
immunosuppression.
AB - We present a case of a multifocal kidney transplant renal cell carcinoma in a 35
year-old lady, presenting 16 years after kidney transplantation, diagnosed during
investigation of recurrent urinary tract infections. The patient underwent a
graft nephrectomy and subsequently maintained on haemodialysis. She remained
disease-free after 4 years of surveillance and thus reactivated on the transplant
list. This case reinforces the fact that immunosuppressive therapy has made
kidney transplantation possible; however, it is accompanied by a higher incidence
of malignancy. It also reinforces the importance of lifelong screening of both
native and renal transplant grafts.
PMID- 28509177
TI - Karyomegalic interstitial nephritis.
AB - Karyomegalic interstitial nephritis is a singular type of progressive chronic
interstitial nephritis. The pathogenesis of this disease is unknown. The present
study reported the case of a 22-year-old man who presented with a long history of
recurrent upper respiratory tract infection episodes secondary to bronchiectasis
and with progressive renal failure. Renal biopsy revealed chronic
tubulointerstitial nephritis and a surprisingly marked karyomegaly specifically
of the tubular epithelium.
PMID- 28509176
TI - Two autosomal dominant polycystic kidney (ADPKD) cases with advanced renal
dysfunction, effectively treated with tolvaptan.
AB - We report here two cases of autosomal dominant polycystic kidney disease (ADPKD)
with renal dysfunction that were treated with tolvaptan. Case 1 was a 47-year-old
man with a glomerular filtration rate (GFR) of 17.0 ml/min/1.73 m2 who received
tolvaptan treatment (30 mg/day). After treatment, kidney pain was alleviated, and
the estimated GFR (eGFR) decline improved from -9.84 ml/min/1.73 m2 per year to
4.08 ml/min/1.73 m2 per year, respectively. The rate of increase in total kidney
volume was reduced from 18 % per year before treatment to 4 % per year following
tolvaptan administration. Case 2 was a 44-year-old man with a GFR of 22.6
ml/min/1.73 m2, and the eGFR decline improved from -5.76 ml/min/1.73 m2 per year
before treatment to -3.12 ml/min/1.73 m2 per year following tolvaptan treatment
(30 mg/day). The rate of increase in total kidney volume was also decreased from
10 % per year before treatment to -7 % per year following tolvaptan
administration. These results suggested that tolvaptan may be effective in
impeding kidney function aggravation and kidney volume increase in ADPKD patients
with advanced renal dysfunction.
PMID- 28509178
TI - Carbonic anhydrase II deficiency: report of a novel mutation.
AB - Carbonic anhydrase II (CAII) deficiency is an autosomal recessive disorder
characterized by renal tubular acidosis, osteopetrosis, recurrent bone fractures,
renal stones, growth failure, and mental retardation. Several cases have been
reported in Saudi Arabia with homozygous mutations in CA2 consistent with a high
degree of consanguinity. We report a case of carbonic anhydrase II deficiency
with short stature, mixed renal tubular acidosis, recurrent bone fractures due to
trivial trauma, recurrent renal stones and cerebral calcification. This patient
was compound heterozygous for a novel CA2 mutation and a previously reported
mutation in Arabs.
PMID- 28509180
TI - A case of histopathologically confirmed infective endocarditis with no
vegetations observed during preoperative diagnosis.
AB - An 81-year-old woman on maintenance hemodialysis (HD) was admitted to the
hospital with fever and repeated positive blood cultures for coagulase-negative
staphylococci. The patient had a history of aortic valve replacement for aortic
valve stenosis (AS). Although one major criterion and two minor criteria from the
Duke criteria were met and therefore infective endocarditis (IE) was suspected
for this case, no definitive diagnosis was made. Vegetations were not observed on
the transesophageal echocardiography, but AS was prominent. The patient was
refractory to antibiotic therapy using vancomycin, and blood cultures did not
convert to negative. To treat the suspected IE and AS, aortic valve replacement
was performed. Although vegetations were not observed in the resected valve, gram
positive cocci were found in clusters, and a histopathological diagnosis of IE
was made. The postoperative blood culture converted from positive to negative,
and the patient was subsequently discharged from the hospital. While relative
risk of IE is high in HD patients, a definitive diagnosis of IE may be difficult
due to calcification of the valve and valve replacement. In HD patients with
bacteremia, suspicion of IE should be aggressively pursued if other sources of
infections are negative, and if the patient is refractory to medical treatment,
surgical treatment may be necessary.
PMID- 28509179
TI - Acute interstitial nephritis with membranous nephropathy in bucillamine-treated
rheumatoid arthritis.
AB - In bucillamine-treated patients, persistent proteinuria caused by membranous
nephropathy (MN) is a major adverse effect affecting the kidneys. We experienced
a case of acute interstitial nephritis (AIN) with MN caused by bucillamine. An 81
year-old Japanese woman with a past medical history of rheumatoid arthritis and
hypertension presented with a fever, epigastric pain, and nausea of 1 week's
duration. She had commenced bucillamine 4 months earlier. At the time of
admission, her baseline creatinine (0.8 mg/dl) had risen to 6.8 mg/dl. A renal
biopsy revealed AIN with concomitant MN. Renal function gradually improved after
bucillamine administration was stopped. In addition to MN, bucillamine can cause
AIN, which requires a renal biopsy for definitive diagnosis. Given the host of
pathological findings that tend to develop in patients using bucillamine,
patients receiving the drug who present with symptoms of acute kidney injury
should undergo a renal biopsy to determine the presence of AIN.
PMID- 28509181
TI - Use of darbepoetin alfa for myelodysplastic syndrome coincident with chronic
kidney disease.
PMID- 28509182
TI - Subacute pulmonary embolism in a hemodialysis patient, successfully treated with
surgical thrombectomy.
AB - A 53-year-old woman was admitted to our hospital with a 1-month history of
gradually progressive resting dyspnea and lumbar backache. For the preceding 6
years, she had received regular hemodialysis for end-stage renal disease caused
by autosomal dominant polycystic kidney disease and had taken tamoxifen for 3
years as post-operative chemotherapy for breast cancer. Before admission, the
patient's symptoms had been attributed to volume overload, based on right
thoracic fluid and leg edema. However, despite volume correction by dialysis
therapy, her symptoms had not improved. The patient was transferred to our
hospital, where she was diagnosed with subacute pulmonary embolism (PE). Emergent
pulmonary thrombectomy was performed using cardio-pulmonary bypass. The patient
was discharged from our hospital on post-operative day 23. Recent reports have
shown that hemodialysis patients have a relatively higher risk of PE compared
with the general population. Our case had additional risk factors for PE: female
sex, decreased protein C level, tamoxifen use, and autosomal dominant polycystic
kidney disease. These factors may have had a synergistic effect on the onset of
PE.
PMID- 28509183
TI - Single low-dose rituximab for the treatment of steroid-resistant nephrotic
syndrome with acute kidney injury.
AB - The efficacy of rituximab for kidney disease, such as frequent relapsing
nephrotic syndrome, has been reported recently. Herein, we report a case of a
patient with acute kidney injury that was steroid-resistant nephrotic syndrome
who responded to a single administration of low-dose rituximab. An 86-year-old
Japanese woman with hypertension presented with severe peripheral edema within
several days after onset. Due to the patient's age, renal biopsy was not
performed, nephrotic syndrome was diagnosed and prednisolone was administered at
40 mg/day on the day after admission. However, anuria developed and hemodialysis
was inevitably initiated on the 5th hospital day. The renal function did not
recover, and the general condition gradually became aggravated. On the 50th
hospital day, 100 mg rituximab was administered, which led to immediate depletion
of CD20-positive cells. The urine volume gradually increased from 2-3 weeks after
the rituximab administration, and the renal function recovered slightly. After 5
weeks, it became possible to wean the patient from dialysis, which had been
applied for 3 months. Rituximab might be an option for the treatment of acute
kidney injury due to steroid-resistant nephrotic syndrome.
PMID- 28509184
TI - Mizoribine-induced severe hyperglycemia in a patient with microscopic
polyangiitis.
AB - A 77-year-old woman had been receiving prednisolone (PSL) for 5 months as
induction therapy for microscopic polyangiitis. Because of repeated elevation of
the antineutrophil cytoplasmic autoantibody titer, we added mizoribine (MZR),
and, 2 months later, the patient developed severe hyperglycemia with low serum
and urinary C-peptide reactivity (CPR). The MZR was, therefore, withdrawn and
insulin therapy was started. One month later, the serum and urinary CPR had
increased and postprandial hyperglycemia had improved. Previous in vitro studies
have shown that MZR can induce hyperglycemia through at least two mechanisms. One
is the alteration of insulin secretion from islet cells, and the other is action
via the glucocorticoid receptor (GR). MZR reduces insulin secretion through the
depletion of intracellular guanosine triphosphate (GTP), which leads to the
inhibition of mitogenesis and induction of beta cell apoptosis. MZR affects
insulin resistance by activating the GR through interaction with the 14-3-3
protein, leading to postprandial hyperglycemia. Although postprandial
hyperglycemia generally appears between 3 and 7 weeks after PSL administration,
that in our patient did not become apparent during 5 months of PSL monotherapy,
but was manifested 2 months after the introduction of MZR, and improved after MZR
had been withdrawn. We conclude from these findings that MZR had been responsible
for the hyperglycemia in our patient.
PMID- 28509185
TI - A case of bacterial peritonitis caused by Roseomonas mucosa in a patient
undergoing continuous ambulatory peritoneal dialysis.
AB - Bacterial peritonitis remains a life-threatening complication of peritoneal
dialysis (PD). Roseomonas is a bacterial genus of pink-pigmented, oxidized, gram
negative coccobacilli that was first named in 1993. Importantly, Roseomonas
mucosa exhibits antibiotic resistance, with significant resistance to
cephalosporin, which is often selected as an empirical antibiotic regimen for
peritonitis in PD patients. We herein report the case of a PD patient with
bacterial peritonitis caused by Roseomonas mucosa that was fortunately identified
using 16S rRNA gene sequencing and successfully treated with ciprofloxacin. Given
that Roseomonas demonstrates resistance to a variety of antibiotics. The
administration of empiric antibiotic therapy based on the recommendation of the
International Society of Peritoneal Dialysis guidelines occasionally fails,
leading to the aggravation of bacterial peritonitis. Hence, nephrologists should
consider Roseomonas as one of the potential causative organisms of peritonitis,
especially when gram-negative bacilli are resistant to cephalosporin and cannot
be identified using standard laboratory methods.
PMID- 28509186
TI - A case of adult Dent disease in Japan with advanced chronic kidney disease.
AB - Dent disease is an inherited tubulopathy caused by a mutation in the CLCN5
chloride channel gene. In cases of Dent disease in Japan (Japanese Dent, J-Dent),
renal function is generally preserved and rarely progresses to advanced kidney
dysfunction. However, the long-term prognosis of J-Dent remains unknown. We
report the case of a 32-year-old man with J-Dent who developed advanced kidney
dysfunction. Since the age of 3 years, he persistently exhibited proteinuria, and
examination of a kidney biopsy specimen indicated focal segmental
glomerulosclerosis (FSGS)-like lesions. Repeated corticosteroid treatments were
found to be ineffective. After the age of 18 years, the patient was lost to
follow-up and treatment was discontinued. The patient presented to our hospital
again at the age of 32 years with advanced kidney dysfunction with low-molecular
weight proteinuria (LMWP), along with proximal tubular dysfunction and
nephrocalcinosis. The patient's 5-year-old nephew was also found to have LMWP
from the age of 7 months. Therefore, Dent disease was suspected and genetic
testing in the patient and his nephew revealed a CLCN5 mutation. Our case report
suggests that J-Dent may cause advanced kidney dysfunction in adulthood, and,
therefore, close collaboration between pediatricians and nephrologists is
essential for the early identification of this complication. When male patients
exhibit chronic kidney disease (CKD) of unknown etiology along with proximal
tubular dysfunction and nephrocalcinosis, Dent disease should be considered.
Investigations of undiagnosed adult J-Dent cases and further research on the
natural history of J-Dent will help us better understand its clinical
characteristics, prognosis, and effective treatment options.
PMID- 28509187
TI - Recurrent proliferative glomerulonephritis with monoclonal immunoglobulin G
deposits leads to rapid graft loss after kidney transplantation: a case report.
AB - We present a case of recurrent proliferative glomerulonephritis with monoclonal
immunoglobulin G (IgG) deposits (PGNMID) that progressed rapidly to allograft
failure. A 56-year-old man had progressed to end-stage renal failure within 1
year after the diagnosis of membranoproliferative glomerulonephritis (MPGN) by
kidney biopsy. He underwent living donor kidney transplantation from his brother
6 months later. Serial allograft biopsies revealed early glomerular deposition of
IgG, C1q, and C3 at post-operative day 26, and gradual progression of the
glomerular deposition and histology of glomerulonephritis. Several
immunosuppressive therapies did not prevent proteinuria, microhematuria, and
graft dysfunction, and the patient returned to hemodialysis at 7 months after
transplantation. Retrospectively, we demonstrated monoclonal IgG3kappa deposition
in the native and allograft kidney, and the patient was diagnosed with recurrent
PGNMID. The serial graft biopsies revealed the pathological details of the
progression of PGNMID. This is a rare case of PGNMID that recurred and progressed
rapidly to graft failure after kidney transplantation.
PMID- 28509188
TI - Atypical triad of IgA nephropathy: reversible acute kidney injury, gross
hematuria, and severe bilateral flank pain.
AB - Reversible acute kidney injury very rarely complicates the course of
immunoglobulin A (IgA) nephropathy. We report an atypical case of reversible
acute kidney injury, gross hematuria, and severe bilateral flank pain as the
presenting triad of IgA nephropathy. Renal biopsy revealed mesangial IgA
deposition without glomerular crescents. The patient's renal dysfunction,
mediated by red cell tubular obstruction, interstitial nephritis, and tubular
necrosis, resolved without intervention. We conclude that IgA nephropathy should
be considered in the differential diagnosis for transient acute kidney injury
with gross hematuria, and should be appropriately treated based on known
prognostic factors.
PMID- 28509189
TI - The importance of medical interview with CKD patient in diagnoses of a family
with Fabry disease.
AB - A 47-year-old Japanese man was admitted to our hospital for evaluation of
proteinuria, which was detected when he was 37 years of age. His creatinine
clearance levels had fallen to 76.3 mL/min/1.73 m2. A kidney biopsy was
conducted, and the patient's low plasma alpha-galactosidase A levels suggested
Fabry disease. After genetic counseling, GLA analysis revealed a novel mutation
p.L387P. Interview with the patient revealed that both his younger brother and
mother suffered from cardiomyopathy and were undergoing cardiological treatment.
They also were positive for proteinuria. About 30 years ago, the patient's cousin
(aged 25) was diagnosed with Fabry disease. He underwent hemodialysis for 9 years
until his death at 42. At that time, the patient and his brother had not been
investigated for Fabry disease so their cousin could not act as a proband for the
brothers. Eventually, the patient, his mother, and his brother were put on enzyme
replacement therapy with agalsidase beta. As this series of cases shows, medical
interviews to collate both medical and family history were essential for the
discovery of Fabry disease in these patients. In addition, being a treatable
genetic disorder, Fabry disease should be listed in the standard differential
diagnoses of systemic and familial diseases, including unknown cause of
nephropathy or cardiomyopathy, for early detection of the disorder.
PMID- 28509190
TI - Tophaceous pseudogout in a patient undergoing peritoneal dialysis.
AB - Calcium pyrophosphate dihydrate deposition disease (pseudogout) is a crystal
arthritis characterized by pyrophosphate dihydrate crystal deposition in the
articular cartilage or synovium. In chronic kidney disease patients, the major
causes of crystal arthritis are calcium oxalate crystals and basic calcium
phosphate crystals. However, pseudogout is apparently infrequent among such
patients. This report describes a rare case of tophaceous pseudogout (tumoral
form of pseudogout) involving the hip joint in a peritoneal dialysis patient, as
revealed by CT scan and synovial fluid aspiration. Fluid aspiration and oral
NSAIDs improved the clinical symptoms. This report is the first to describe
tophaceous pseudogout in a peritoneal dialysis patient, which suggests that
pseudogout should be suspected in dialysis patients with unexplained arthritis.
PMID- 28509191
TI - Probable light- and heavy-chain deposition disease in a patient with nodular
diabetic glomerulosclerosis.
AB - We report a case of probable light- and heavy-chain deposition disease (LHCDD) in
a diabetic patient, a rare and educational case. The patient was a 71-year-old
man having a long history of uncontrolled diabetes mellitus with retinopathy. He
showed heavy proteinuria and renal insufficiency, and did not have paraproteins.
Renal biopsy revealed nodular glomerulosclerosis with severe mesangial widening
and microaneurysm. Immunofluorescence (IF) showed weak staining of kappa light
chain, IgG and C1q along glomerular basement membrane (GBM). At first, we
interpreted these IF findings to be nonspecific, thus we diagnosed as diabetic
nodular glomerulosclerosis. Later, we recognized one of a few case reports of
monoclonal immunoglobulin deposition disease (MIDD) in diabetic patients, and
reconsidered the first diagnosis. The added electron microscopy (EM) showed
obvious electron-dense materials in GBM, while tubular basement membrane deposits
were not identified. A concurrence of LHCDD and diabetic nodular
glomerulosclerosis may be suggested in this case. Like this case, IF staining in
MIDD is often weak, so it is difficult to diagnose MIDD accurately without EM.
Reports of MIDD in diabetic patients are extremely rare, possibly due to being
often overlooked. This case emphasizes that overall pathological examination
including IF and EM is important for the accurate differentiation of nodular
glomerulosclerosis, even in diabetic patients.
PMID- 28509192
TI - Two cases of minor glomerular abnormalities with proteinuria disproportionate to
the degree of hypoproteinemia.
AB - We experienced two female cases of minor glomerular abnormalities with
proteinuria disproportionate to the degree of hypoproteinemia. They did not have
adequately large amounts of urine protein so as to cause nephrotic syndrome;
however, we were unable to determine any cause of hypoproteinemia other than
proteinuria. The renal pathology revealed foot process effacement, and hyaline
droplet degeneration, suggesting urine protein hyper-reabsorption in the proximal
convoluted tubule. Therefore, we thought these cases involved pathophysiological
conditions, such as minimal change nephrotic syndrome. In both cases, the
hypoproteinemia improved following the administration of oral prednisolone. As in
past reports, it is thought that the principal causative factor of
hypoalbuminemia in patients with nephrotic syndrome is a catabolic reaction after
the serum albumin filtered at the glomerulus is reabsorbed in the proximal
tubule. In the present two cases, it is supposed that a large amount of urine
protein was filtered in the primitive urine; however, the amount of final urinary
protein did not reach the nephrotic range because most of it was reabsorbed in
the proximal tubule and reabsorbed in the blood after being disintegrated into
amino acids by a catabolic reaction. Or we might simply observe the process
before the case 1 got nephrotic syndrome and the healing process of nephrotic
syndrome in the case 2.
PMID- 28509193
TI - Acute severe liver dysfunction induced by febuxostat in a patient undergoing
hemodialysis.
AB - A 58-year-old man with chronic kidney disease (CKD) was admitted to our hospital
for hemodialysis (HD) therapy. He had been administered allopurinol (100 mg/day)
before hospitalization, and we replaced it with febuxostat (10 mg/day), a new
xanthine oxidase inhibitor. Levels of aspartate aminotransferase, alanine
transaminase (ALT), and lactate dehydrogenase were within the normal ranges in
the morning before febuxostat administration, but 6 h after administration, these
parameters increased markedly to approximately 10 times the levels before
administration. Although we stopped administering febuxostat, his serum potassium
levels increased at a rate of 1 mmol/L every 12 h, and he had to undergo HD daily
to lower the serum potassium levels. The levels of liver function test parameters
peaked on the fourth hospital day (ALT, 1134 IU/L; AST, 1485 IU/L; and LDH, 1869
IU/L) and recovered to normal ranges on the 13th hospital day. In this case,
febuxostat appeared to have a relationship with acute liver dysfunction in the
clinical course. Therefore, it would be important to check liver function test
parameters frequently after febuxostat initiation and also to initiate a lower
than usual dose of febuxostat, especially in patients with CKD and those who are
undergoing HD.
PMID- 28509194
TI - Recurrent IgA nephropathy complicated with Crohn's disease after renal
transplantation.
AB - A 27-year-old man was diagnosed with IgA nephropathy and Crohn's disease. He had
been diagnosed with proteinuria and hematuria since he was 20 years old. Diarrhea
had been a continuing problem during the past 5 months. Neither corticosteroid
therapy nor tonsillectomy was performed. Hemodialysis was required at age of 30,
while the symptoms of Crohn's disease were ameliorated by an elemental diet. He
received a renal transplant from his mother 4 months after starting dialysis
therapy. The initial immunosuppression therapy consisted of methylprednisolone,
mycofenolate mofetil, cyclosporine, and basiliximab. Eight months after
transplantation, proteinuria and hematuria appeared and serum creatinine was 1.4
mg/dL. Relapse of IgA nephropathy was confirmed by the one-year protocol biopsy.
He had suffered from tonsillitis at 32 months after the transplantation. Urinary
protein increased to 3 g/day and serum creatinine was elevated to 2.04 mg/dL.
Renal biopsy was performed 2 weeks after the urinary findings were aggravated.
The cellular crescents constituted 36 % of the glomeruli. The findings of
rejection were not confirmed in both biopsies. Tonsillectomy was performed
thereafter. No additional immunosuppressive therapy was added. Proteinuria and
hematuria disappeared at 4 and 20 months, respectively, after tonsillectomy, even
when the symptoms of Crohn's disease worsened 69 months and 89 months after
transplantation. A renal biopsy was performed 101 months after transplantation.
Although IgA in the mesangium area was confirmed by immunohistochemical staining,
no active lesion was seen. Tonsillectomy along with immunosuppressants for the
graft might be an effective treatment for some patients with active recurrent IgA
nephropathy.
PMID- 28509195
TI - Mixed cryoglobulinemia and secondary membranoproliferative glomerulonephritis
associated with ehrlichiosis.
AB - Ehrlichiosis is a tick-borne disease with diverse clinical presentations, ranging
in severity from a flu-like illness with fever and myalgias to a serious systemic
disease with multisystem organ failure. Nephrotic syndrome has been reported
previously in two cases of human ehrlichiosis. A kidney biopsy revealed minimal
change disease in one of those patients. Herein, we present the case of a 40-year
old man with ehrlichiosis who developed nephrotic syndrome, cryoglobulinemia, and
secondary membranoproliferative glomerulonephritis (MPGN). The patient originally
presented with shortness of breath, diffuse myalgias, headache, and lower
extremity edema. He subsequently developed acute kidney injury and underwent
kidney biopsy which showed MPGN and acute tubular injury. A tick-borne disease
panel was positive for IgM and IgG to Ehrlichia chaffeensis. Serum testing
revealed type 3 mixed cryoglobulinemia with no evidence of hepatitis C infection.
The cryoprecipitate contained IgM and IgG antibodies to E. chaffeensis.
Cryoglobulinemia is frequently associated with infections, particularly hepatitis
C; however, our case is the first to describe ehrlichiosis associated with
cryoglobulinemia and secondary MPGN.
PMID- 28509196
TI - Acquired Fanconi syndrome due to long-term adefovir administration in a patient
with IgG-kappa monoclonal gammopathy and kappa Bence-Jones protein.
AB - A 77-year-old man was admitted to our hospital for a right femoral neck fracture.
He had been prescribed lamivudine for chronic hepatitis B infection for 11 years,
and adefovir was added 5 years ago. After hospitalization, a right femoral head
prosthesis was performed successfully, but an unknown hypokalemia was revealed.
Hypophosphatemia, hypouricemia, glucosuria, and panaminoaciduria were also
revealed, and multiple microfractures were detected by bone scintigraphy. We
diagnosed him as 'osteomalacia associated with Fanconi syndrome,' which was
likely due to the adefovir. Moreover, a monoclonal IgG-kappa and a kappa Bence
Jones protein were detected in his serum and urine, respectively. We switched
from adefovir plus lamivudine to entecavir and started calcitriol. His excessive
urinary beta2-microglobulin excretion and glucosuria had decreased dramatically
at 10 weeks after the modification of drugs; those of the phosphate, uric acid
and total protein, however, continued. Renal biopsy specimens obtained at 10
weeks after discontinuation of adefovir revealed focal tubular atrophic changes
with/without inflammatory cells, which were predominantly observed next to
glomeruli. Kappa-dominant staining was not observed in either glomeruli or
tubules with immunostaining by the enzyme-labeled antibody method. Electron
microscopy revealed neither crystalline structures in the cytoplasm of proximal
tubules nor electron-dense deposits. Because of the remarkable proportional
reduction of other urinary protein fractions, urinary M-peak appeared 26 weeks
after discontinuation of adefovir, but the net amounts of the fraction decreased
gradually.
PMID- 28509197
TI - Adefovir-induced Fanconi syndrome: diagnostic pearls and perils of late or missed
diagnosis.
AB - Low-dose adefovir therapy has been increasingly recognised as a cause of Fanconi
syndrome. Being relatively novel, early diagnosis is both fraught with difficulty
and yet of paramount importance given its far-reaching consequences, many of
which are amenable to treatment. We discuss a patient who presented with
hypokalemia and other electrolyte abnormalities suggestive of Fanconi syndrome
whilst on adefovir for hepatitis B. A trans-tubular potassium gradient (TTKG =
9.4) and urinary fractional phosphate excretion (39.4 %) consistent with renal
potassium and phosphate wasting together with euglycemic glycosuria,
aminoaciduria and hypophosphatemic osteomalacia supported the diagnosis of
adefovir-induced Fanconi syndrome. With the cessation of the culprit drug, the
patient has achieved partial recovery after 9 months. A high index of suspicion
coupled with regular symptom surveillance and electrolyte monitoring is
recommended in the course of adefovir therapy.
PMID- 28509198
TI - Localized cystic disease of the kidney: case report and review of the literature.
AB - Localized cystic disease of the kidney (LCDK) is a benign and non-progressive
renal anomaly that may initially be confused with autosomal dominant polycystic
kidney disease (as in the index case) or cystic neoplasms. It is best diagnosed
with contrast-enhanced CT scan demonstrating the characteristic features of an
unencapsulated mass of smooth-walled cysts with enhancing renal parenchyma
between them. It is most often an incidental finding, but may present with flank
pain or haematuria. Hypertension and renal impairment are uncommonly associated
with LCDK. A complete physical examination and comprehensive family history are
important to exclude other acquired or inherited causes of cystic kidney disease
and to avoid unnecessary diagnostic procedures or nephrectomy. We describe a case
manifesting many of the typical features of the condition and review previously
published cases to describe the natural history and presentation of this rare
entity.
PMID- 28509199
TI - Graft versus host disease-dependent renal dysfunction after hematopoietic stem
cell transplantation.
AB - Nephropathy is an important complication in hematopoietic stem cell
transplantation (HSCT) wherein multifactorial causes, i.e., radiation, drug
toxicity, graft versus host disease (GVHD), are thought to contribute renal
dysfunction. Here, we report a 10-year-old boy with high-risk acute myelocytic
leukemia and severe but partially reversible renal dysfunction. The patient
initially received umbilical cord blood transplantation (UCBT) with CY 120 mg/kg
and kidney unshielded 12 Gy of total body irradiation. After the leukemic
relapse, he received allogenic bone marrow transplantation (BMT) 270 days after
the first transplantation. Two months later, his renal function started to
deteriorate and urinary protein increased gradually to 1 g/day. Four months after
BMT, by the symptoms of severe GVHD, the dose of tacrolimus, utilized to avoid
GVHD, was increased although his serum Cre level elevated to 2.97 mg/dL. Serum
Cre level improved to 2.0 mg/dL paralleled with GVHD improvement. Renal
histological findings showed severe interstitial edema, features of thrombotic
microangiopathy (TMA), and C4d deposition along the glomerular capillaries and
peritubular capillaries. We suggested that control of GVHD had benefitted to
ameliorate renal function of the patient. Treatment for GVHD improved renal
dysfunction and TMA of our patients. Moreover, renal biopsy was powerful to
elucidate the exact origin of renal dysfunction after HSCT.
PMID- 28509200
TI - Staphylococcal empyema secondary to IgA nephropathy.
AB - A 27-year-old male patient, applied to the emergency unit with complaints of high
fever, nausea, vomiting, and hematuria. In his physical examination, fever was 38
degrees C with normal findings in all other systems. The laboratory values were
as follows: urea 58 mg/dL, creatinine 2.4 mg/dL, white blood cell count 15.9K/MUL
(PNL: 79 %). In his urine analysis; +1 proteinuria and +3 hematuria were
detected. Kidney biopsy was performed. Kidney biopsy interpreted in favor of IgA
nephropathy. As the patient had tonic-clonic seizures, cranial CT examination was
performed. In the cranial CT, there was a subdural effusion in the anterolateral
area of the right cerebral hemisphere with the left shift in the midline
secondary to the effusion. Empyema fluid, which was drained postoperatively, was
cultured. In the direct examination of the empyema fluid, Gram positive cocci and
abundant amount of PNLs were observed. There was no growth in the culture.
Although the most commonly encountered agents for post-infectious
glomerulonephritis are streptococcus infections, it has been reported that
glomerulonephritis attacks may be rarely observed due to staphylococcus
infections. Proliferative glomerulonephritis cases are rarely encountered
conditions characterized by mesangial IgA accumulations secondary to
staphylococcus infections.
PMID- 28509201
TI - Diuretics-assisted treatment of chronic laxative abuse.
AB - Hypopotassemia with acid-base imbalance caused by laxative abuse is one of the
disorders that nephrologists can be consulted for. Although laxatives are not
supposed to form psychological dependence in themselves and their abuse should be
cured theoretically by just finishing the overdose, the patients often resist
treatment due to unpleasant symptoms such as edema and worsening constipation.
Thus, chronic laxative abuse is often regarded as a drug addiction. We report a
successfully treated case of chronic laxative abuse, where drastic reduction of
laxatives was achieved by applying diuretics. After drastic reduction of
laxatives, diuretics were added until they eased edema and bloating so that the
patient could feel them to be tolerable, paying attention to lab data such as
potassium and renal function. The diuretics, which substituted for laxatives in
fluid control, could be tapered off over 3 months without any withdrawal symptoms
or a need of additional laxatives. Our experience of simple but successful
treatment of chronic laxative abuse emphasizes importance of physical management
and suggests that there are cases where the two different kinds of drugs,
laxatives and diuretics, can practically be regarded as swappable in the
treatment of laxative abuse. This presentation should contribute to accumulation
of knowledge in how to treat chronic laxative abuse where no standardized method
is established yet.
PMID- 28509202
TI - Isolated complex renal cyst mimicking kidney mass.
AB - Hydatidosis is an endemic parasitic disease in Mediterranean region, Middle east,
Australia, parts of Africa, Latin America and Turkey. The cysts are mostly
evident in the liver or lungs, while urinary tract involvement is uncommon,
comprising only 2-4 % of all cases. Isolated renal involvement is extremely rare.
Its diagnosis may be difficult because of nonspecific complaints and absence of
pathognomonic laboratory findings except from hydatiduria. Although radiological
studies have a more important role in the diagnosis, they cannot always show a
specific sign or lesion for hydatid disease. Herein we present a rare case with
isolated renal hydatid cyst mimicking a renal mass treated with right radical
nephrectomy. Isolated renal cyst hydatid should be considered in differential
diagnosis of both cystic and solid renal masses.
PMID- 28509204
TI - Erratum to: Diuretics-assisted treatment of chronic laxative abuse.
PMID- 28509203
TI - Chronic renal failure due to amyloid nephropathy caused by chronic infection
after total hip replacement.
AB - A 75-year-old woman was admitted to our hospital because of proteinuria, pitting
edema on the foot, and renal impairment. She had undergone total hip replacement
(THR) for femoral neck fracture at the age of 66. Nine years later, she met with
an accident during farming and was treated at an emergency hospital for severe
general trauma. On the basis of systemic symptoms, she was diagnosed with
nephrotic syndrome. Renal biopsy by Congo-red staining and electron microscopy
revealed amyloid deposition on glomeruli, interstitium, and interlobar arteries.
The amyloid was immunohistochemically identified as AA amyloidosis. The patient
eventually required maintenance hemodialysis because of impaired renal function.
AA amyloidosis is an unusual complication of intractable inflammation. Chronic
infection with abscess occurred around the artificial hip joint following THR and
possibly induced secondary amyloidosis. THR is a common and necessary procedure
adopted for femoral neck fracture. Orthopedic surgeons should, however, carefully
monitor the occurrence of chronic infection after THR because such an infection
could lead to renal dysfunction and/or failure via AA amyloidosis in rare cases.
PMID- 28509205
TI - An 11-year-old girl with antineutrophil cytoplasmic antibody-associated
glomerulonephritis identified by a school urinary screening program.
AB - Antineutrophil cytoplasmic autoantibody-associated glomerulonephritis (GN) in
childhood is rare and has a poor prognosis. We report an 11-year-old girl with
renal-limited antineutrophil cytoplasmic autoantibody-associated vasculitis.
Proteinuria and hematuria were first detected by a school urinary screening (SUS)
program. Histopathological examination revealed pauci-immune necrotizing GN. She
did not display purpura or peripheral neuropathy. She was diagnosed with
antineutrophil cytoplasmic autoantibody-associated GN based on proteinuria, high
serum titers of antineutrophil cytoplasmic autoantibodies (ANCAs), and pauci
immune necrotizing GN. The patient was treated with combination therapy,
consisting of methylprednisolone and urokinase pulse, prednisolone, mizoribine
(MZB), warfarin, and dilazep hydrochloride. At 2 months after treatment, urinary
protein excretion was decreased and the hematuria had disappeared, while the
serum titer of ANCAs was also decreased. The dose of prednisolone was tapered,
and proteinuria and hematuria later disappeared at 9 months after treatment. In
conclusion, we reported an 11-year-old girl with renal-limited antineutrophil
cytoplasmic autoantibody-associated vasculitis early identified by a SUS program
and treated with multi-drug combination therapy including MZB. On the basis of
our results, we believe that a SUS programs may be effective for the early
identification and treatment of children with renal-limited antineutrophil
cytoplasmic autoantibody-associated vasculitis.
PMID- 28509206
TI - Peritoneopericardial communication after aortic valve replacement in a peritoneal
dialysis patient.
AB - A 73-year-old male undergoing peritoneal dialysis (PD) for end-stage renal
disease due to diabetic nephropathy was diagnosed with aortic stenosis and was
admitted to our hospital in September, 2009. The patient underwent replacement of
the ascending aorta with an artificial blood vessel plus aortic valve replacement
without any notable complications. PD was restarted 3 days after the surgery and
large amounts of light red fluid from the drain placed in the pericardium were
observed just after resumption of PD solution. The patient was diagnosed with
peritoneopericardial communication. PD was discontinued and hemodialysis was
performed only with intermittent lavage of the peritoneal cavity. The amount of
drainage was spontaneously decreased, and on the 17th day after surgery, PD was
resumed. The patient is undergoing PD without recurrence of peritoneopericardial
communication, 59 months after the onset of symptoms. Peritoneopericardial
communication in a patient with PD developing after open-heart surgery is rare
because such a case has been documented in only one case report. However, since
massive pericardial effusion may cause severe cardiac problems, we consider that
the communication between the peritoneal cavity and the pericardium needs to be
checked for in patients with PD after cardiac surgery.
PMID- 28509207
TI - Improvement in karyomegalic interstitial nephritis three years after ifosfamide
and cisplatin therapy by corticosteroid.
AB - Long-term nephrotoxicity of ifosfamide is occasionally progressive, and, in such
case, there has been no specific treatment to prevent progression. It has been
reported that the presence of karyomegalic interstitial nephritis, which is rare
type of interstitial nephritis, may be related to ifosfamide-induced nephropathy
with poor prognosis and resistant to the immunosuppressive therapy. A 15-year-old
boy presented with progressive nephrotoxicity 3 years after systemic chemotherapy
with ifosfamide and cisplatin for the treatment of osteosarcoma. Renal biopsy
revealed the severe tubulointerstitial nephritis with tubular atrophy and focal
global and segmental glomerular sclerosis. It also showed tubular epithelial
cells with variably sized nuclei, some of which were massively enlarged, abnormal
hyperchromatic, irregular shaped, and bizarre-appearing. These morphological
changes were suggestive of the histology of karyomegalic interstitial nephritis.
Corticosteroid retarded the progression of nephrotoxicity. The present case is
the first report, suggesting that corticosteroid was effective against the late
onset renal toxicity by ifosfamide therapy. Our case also suggests that
karyomegalic interstitial nephritis may be the result of long-term nephrotoxicity
of ifosfamide. Since concurrent treatment with cisplatin is one of the risk
factors for ifosfamide nephrotoxicity, there is a possibility that cisplatin may
have a synergetic effect with ifosfamide for producing karyomegalic interstitial
nephritis.
PMID- 28509208
TI - Rapidly developed diffuse myocardial calcification 13 days after septic shock in
a hemodialysis patient.
PMID- 28509210
TI - List of referees.
PMID- 28509209
TI - Tocilizumab-induced remission of nephrotic syndrome accompanied by secondary
amyloidosis and glomerulonephritis in a patient with rheumatoid arthritis.
AB - Rheumatoid arthritis (RA) is an autoimmune-mediated systemic disorder that
primarily affects the musculoskeletal system. Patients with RA often present with
kidney diseases, such as nephrotic syndrome. Causes of nephrotic syndrome include
membranous nephropathy, IgA nephropathy and secondary amyloidosis. Recently,
biological agents, including anti-tumor necrosis factor alpha and anti
interleukin 6 (IL-6) receptor antibodies, have been used for the treatment of RA.
Anti-IL-6 receptor antibody therapy is believed to ameliorate RA-related kidney
diseases, as IL-6 plays a central role in the pathogenesis of RA. We, herein,
present the case of a patient with RA and related nephrotic syndrome whose
proteinuria completely disappeared 1 month after tocilizumab treatment. A light
microscopic examination of the pretreatment kidney biopsy specimen showed active
glomerulonephritis with fibrocellular crescents and the deposition of amorphous
substances stained weakly with hematoxylin-eosin and strongly with the Dylon
method. Electron microscopy revealed the accumulation of microtubules ranging
from 10 to 20 MUm in width, primarily in the mesangial lesion. Amyloid A (AA)
protein was positively stained in the mesangial area and vascular wall on
immunohistochemistry. The final histologic diagnosis was RA-related
glomerulonephritis and secondary AA amyloidosis. This case indicates that
biological treatment targeting IL-6 is a promising therapeutic option for the
treatment of kidney diseases associated with RA.
PMID- 28509211
TI - A case report of the anti-glomerular basement membrane glomerulonephritis with
mesangial IgA deposition.
AB - A 46-year-old Japanese male with a past medical history of microscopic hematuria
presented with nausea, vomiting, and abdominal pain for which he had been
diagnosed with rapidly progressive glomerulonephritis with a peak serum
creatinine of 6.6 mg/dL and anti-glomerular basement membrane antibody of 214 EU.
Light microscopy showed cellular crescent formation, and immunofluorescence
illustrated both linear staining of IgG along the glomerular basement membrane
and granular staining of IgA and C3 in the mesangial area; however, the PAS
staining of mesangial expansions and mesangial proliferations were not observed.
Clinical and histological findings suggested anti-glomerular basement membrane
glomerulonephritis with mesangial IgA deposition, suggesting IgA nephropathy, a
rare condition.
PMID- 28509212
TI - Central diabetes insipidus and adipsia due to astrocytoma: diagnosis and
management.
AB - Adipsia and/or diabetes insipidus is rarely a direct complication of astrocytoma.
We report a young man with recurrence of anaplastic astrocytoma who presented as
severe hypernatremia. This case highlights key diagnostic and therapeutic
challenges: (1) the interpretation of the response to exogenous vasopressin in a
patient with steroid-induced hyperglycemia and (2) the potential risk of brain
edema and herniation if excess water is prescribed along with vasopressin
supplementation. The patient was successfully managed with prescribed fluid
replacement, daily weights, and regular electrolyte monitoring but no exogenous
vasopressin for 8 months until he succumbed to his tumor.
PMID- 28509213
TI - A case of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH)
associated with lupus erythematosus in the central nervous system.
AB - We report on a case of the syndrome of inappropriate secretion of antidiuretic
hormone (SIADH) associated with lupus erythematosus in the central nervous system
(CNS). A 73-year-old woman with essential hypertension suddenly demonstrated
consciousness disturbance. Upon her admission, laboratory data showed significant
hyponatremia (114 mEq/L) and a lack of body fluid loss. Diminished free water
excretion (urine osmolality 684 mOsm/kg) and normal urine Na excretion (FENa 1.70
%) were consistent with the diagnosis of SIADH, which was confirmed by an
inappropriately high concentration of plasma antidiuretic hormone (ADH) (15.3
pg/mL at 256 mOsm/kg of plasma osmolality). The hyponatremia was corrected by a
combination of oral water intake restriction and saline infusion with furosemide
administration until the 20th hospital day. Simultaneously, the presence of
exudative pleural effusion in both chest cavities, suggesting the existence of
pleuritis, and high titer of anti-nuclear antibody (ANA, 5120*) and anti-double
strand DNA antibody (6500 IU/mL), indicated the subclinical development of
systemic lupus erythematosus (SLE), although the diagnostic criteria were not
satisfied at that time. On the 34th hospital day, the sudden onset of unknown
consciousness disturbance confirmed the diagnosis of SLE as CNS lupus. In
previous case reports on SLE and/or SIADH, a few cases in which SLE and SIADH
developed concomitantly regularly showed high immunological activities, as in our
case. Some common pathophysiological bases might be involved in the concomitant
appearance of those disorders.
PMID- 28509214
TI - Severe metabolic alkalosis, hypokalemia, and respiratory acidosis induced by the
Chinese herbal medicine yokukansan in an elderly patient with muscle weakness and
drowsiness.
AB - Yokukansan is a Chinese herbal medicine containing licorice that has been shown
to alleviate the behavioral and psychological symptoms of Alzheimer's disease,
with few adverse effects. Increasing numbers of patients with Alzheimer's disease
in Japan are now being treated with this drug. However, yokukansan should be used
with caution because of its potential to induce pseudoaldosteronism through the
inhibition of 11-beta-hydroxysteroid dehydrogenase type 2, which metabolizes
cortisol into cortisone. We present the case of an 88-year-old woman with a
history of Alzheimer's disease who was transferred to our emergency department
because of drowsiness, anorexia, and muscle weakness. Her blood pressure was
168/90 mmHg. Laboratory data showed serum potassium of 1.9 mmol/l, metabolic
alkalosis (pH 7.54; HCO 3- , 50.5 mmol/l; chloride, 81 mmol/l; sodium, 140
mmol/l), and respiratory disorders (pCO2, 60.5 mmHg; pO2, 63.8 mmHg). Plasma
renin activity and aldosterone concentration were suppressed, and urinary
potassium excretion was 22 mmol/l (calculated transtubular potassium gradient
12.9). An electrocardiogram showed flat T-waves and U-waves with ventricular
premature contractions. Echocardiography denied volume depletion. Medical
interview disclosed that she had been treated with a Chinese herbal medicine
(yokukansan) containing licorice. The final diagnosis was pseudoaldosteronism and
respiratory acidosis induced by licorice. Hypokalemia, metabolic alkalosis, and
respiratory acidosis all subsided shortly after the discontinuation of yokukansan
and initiation of intravenous potassium replacement. This case highlights the
need for nephrologists to consider the possible involvement of Chinese herbal
medicines, including yokukansan, when they encounter hypokalemia in elderly
patients.
PMID- 28509215
TI - De novo acute hepatitis B in myeloperoxidase-specific anti-neutrophil cytoplasmic
autoantibody-related microscopic polyangiitis treated with corticosteroids.
AB - An 82-year-old female was referred to our hospital because of low-grade fever,
anemia, and rapidly progressive nephritic syndrome. Her laboratory data showed
mild proteinuria, mild renal failure, and the presence of myeloperoxidase
specific anti-neutrophil cytoplasmic autoantibody. A skin biopsy specimen taken
from the erythematous purpura revealed neutrophilic infiltration around the blood
vessels with fibrinoid changes in the vessel walls. A renal biopsy specimen
revealed segmental necrotizing glomerulonephritis with fibro-cellular crescent
formation without deposits of immunoglobulin or complement components, indicating
microscopic polyangiitis. The use of corticosteroid treatment, including
intravenous methylprednisolone, improved renal failure. After 4 years with low
dose maintenance corticosteroid therapy, she developed de novo acute hepatitis B,
and entecavir was remarkably effective, showing a rapid recovery from liver
dysfunction with jaundice. To prevent hepatitis B virus (HBV) reactivation and de
novo acute hepatitis B induced by immunosuppressive or cytotoxic therapy,
including corticosteroids alone, the measurement of HBV-related serological
markers needs to be performed prior to the initiation of such therapy, even in
renal diseases.
PMID- 28509216
TI - A distinct lymphocyte distribution in relapse after rituximab for steroid
dependent nephrotic syndrome.
AB - Rituximab (RTX) is a new steroid-sparing therapy for childhood steroid-dependent
nephrotic syndrome (NS). However, relapses frequently occur immediately after
CD19 recovery. We report the cases of two steroid-dependent NS patients treated
with RTX followed by mizoribine (MZB). One patient relapsed, and the other
developed proteinuria after CD19 recovery until the MZB was replaced by
mycophenolate mofetil. These patients exhibited different lymphocyte phenotypes,
with the CD4+/CD8+ profile favoring CD8+ T lymphocytes, while CD3+ HLA-DR
expressing activated T lymphocyte expansion occurred in the relapsed patient.
Based on these findings, we suggest that T cell activation may influence outcome
and that phenotypic analysis in addition to B cell monitoring may facilitate the
detection of NS relapse.
PMID- 28509217
TI - Scleroderma renal crisis in a newly diagnosed mixed connective tissue disease
resulting in dialysis-dependent chronic kidney disease despite angiotensin
converting enzyme inhibition.
AB - Mixed connective tissue disease (MCTD) is a rheumatic disease with a combination
of multiple connective tissue disorders, which includes dermatomyositis or
polymyositis, systemic sclerosis, systemic lupus erythematosus, rheumatoid
arthritis and Sjogren's syndrome. It affects various organs of the body, which
includes the lungs, heart, kidneys, joints, muscles and the haematological
system. Here, we report a case of MCTD consisting of scleroderma, Sjogren's
syndrome and polymyositis complicated by scleroderma renal crisis (SRC) but with
negative anti-nuclear antibody (ANA), anti-Scl 70 and anti-centromere antibodies.
The patient was started on captopril for the treatment of SRC but developed
chronic kidney disease despite adequate blood pressure control with angiotensin
converting enzyme inhibitor (ACEi).
PMID- 28509218
TI - Acute kidney injury due to acyclovir.
AB - Acyclovir is an antiviral agent widely used in herpetic infections in children.
Although acyclovir is generally well tolerated, severe nephrotoxicity has been
reported in some cases. In this report, we present a 16-year-old girl who
developed acute renal failure due to acyclovir treatment and who needed
repetitive hemodialysis. Renal biopsy was performed in order to confirm the
diagnosis. A diagnosis of drug-related acute tubulointerstitial nephritis with
focal tubular necrosis was made.
PMID- 28509219
TI - Atypical hemolytic uremic syndrome with MCP mutations preceded by respiratory
infection.
AB - A 14-year-old boy was referred to our hospital with general fatigue and sore
throat. A chest X-ray and computed tomography revealed diffuse bilateral
bronchitis. A laboratory examination showed anemia, thrombocytopenia, and renal
insufficiency. He had a past medical history of hemolytic uremic syndrome (HUS)
without diarrhea at the age of 3; moreover, his elder brother suffered from HUS
at the age of 12. These findings indicated that the patient had a familial
relapsing form of HUS (atypical HUS). Therefore, he was immediately treated with
plasma exchange (PE), as suggested by guidelines, obtaining complete remission.
Fifteen months later, he suffered another relapse of atypical HUS preceded by
respiratory infection and was cured again with PE. His ADAMTS-13 activity was
normal and its inhibitory antibody was undetectable. Two different mutations were
found in the gene encoding membrane cofactor protein (MCP). Respiratory
infections preceded all three episodes of HUS, but we could not detect the
pathogenic agent. Although the long-term outcomes of patients with atypical HUS
who have mutations in the MCP gene appear favorable, recurrences are nevertheless
frequent. Few reports have described Japanese patients with atypical HUS and
complement regulatory abnormalities. This is the first report of a Japanese
patient with atypical HUS and mutations in the MCP gene.
PMID- 28509220
TI - A case presenting with the possible relationship between myeloperoxidase
antineutrophil cytoplasmic antibody-associated glomerulonephritis and membranous
changes of the glomerular basement membrane.
AB - A 72-year-old woman exhibited elevated serum myeloperoxidase-antineutrophil
cytoplasmic antibody (MPO-ANCA) levels since 2006. Her serum creatinine (sCr)
levels increased from 0.5 to 1.62 mg/dl in a stepwise pattern with proteinuria
and hematuria up to January 2011. Renal biopsy indicated global sclerosis (14 %),
fibrocellular crescents (28 %), and Swiss cheese-like appearance of the
glomerular basement membrane (GBM) on light microscopy. IgG4 staining was
negative. Immunofluorescent examination indicated granular staining with IgG and
C3 along the GBM. MPO-ANCA-associated glomerulonephritis with membranous
nephropathy (MN) was diagnosed. As chronic changes were relatively evident in the
renal biopsy specimen without acute augmentation of renal function,
immunosuppressive therapy was not administered. Thereafter, rapidly progressive
renal dysfunction occurred (sCr, 3.67 mg/dl in May 2011) with proteinuria (~2
g/day), hematuria, and elevated serum MPO-ANCA levels. Therefore, a second renal
biopsy was performed in May 2011, indicating global sclerosis (42 %) and cellular
crescents (35 %) on light microscopy. Electron microscopy indicated electron
dense deposits in the GBM and mesangial lesions. Steroid therapy was subsequently
initiated, and the patient's renal function partially improved. MPO-ANCA levels
decreased to within normal limits and hematuria disappeared. MPO-ANCA-associated
glomerulonephritis with MN is a rare dual glomerulopathy. However, complication
should be considered when urinary protein appears in large amounts. Secondary MN
was suspected due to the lack of IgG4 staining and distribution of electron-dense
deposits to the mesangial lesion. Renal dysfunction occurring in a stepwise
pattern may be attributed to intermittent augmentation in MPO-ANCA-associated
glomerulonephritis.
PMID- 28509221
TI - Development of systemic lupus erythematosus in an elderly male hemodialysis
patient with pleuritis.
AB - This report describes a 70-year-old man who developed systemic lupus
erythematosus (SLE) during treatment with maintenance hemodialysis. At initiation
of maintenance dialysis, the etiology of end-stage renal disease (ESRD) was
diabetic nephropathy and no clinical symptom or laboratory data suggested SLE.
Fever, pleural effusion that did not respond to ultrafiltration, and
immunological findings such as low complement and elevated anti-double-strand DNA
antibody level appeared 4 years after maintenance dialysis initiation.
Immunosuppressive therapy with corticosteroids improved these abnormalities
remarkably. This case underscores the necessity of considering SLE in the
differential diagnosis of pleural effusion with male ESRD patients, even if
another etiology of ESRD exists.
PMID- 28509222
TI - Fabry's disease discovered with chance urinary mulberry cells: a case report.
AB - Fabry's disease (FD) is a rare X-linked lysosomal storage disorder. Novel enzyme
replacement therapy (ERT) at an early stage can slow the progression of
cardiovascular and renal dysfunction. Urinary mulberry cells are occasionally
found in renal FD. We report a case of variant FD in which detection of urinary
mulberry cells led to an early diagnosis. A 36-year-old Japanese man was referred
to our hospital because mulberry cells had been detected during urinalysis.
Proteinuria and renal dysfunction were not observed. His plasma alpha
galactosidase activity was very low. Renal biopsy revealed typical foamy changes
in the glomerular podocytes and tubular epithelial cells that are found in renal
FD. Based on the detection of urinary mulberry cells, we successfully started ERT
before the patient's renal function deteriorated. Clinical nephrologists and
laboratory technicians should recognize the importance of screening for mulberry
cells during urinalysis as this is a simple, inexpensive, and non-invasive method
for diagnosing FD.
PMID- 28509223
TI - Lupus nephritis class I accompanied by tubulointerstitial nephritis with marked T
lymphocyte infiltration in an HTLV-1 positive patient.
AB - We herein describe the case of a 40-year-old Japanese male who was admitted to
our hospital because of a continuous remittent fever lasting 1 month. He
fulfilled the items of the classification criteria for the diagnosis of systemic
lupus erythematosus (SLE). The administration of 20 mg per day of oral
prednisolone completely diminished his clinical symptoms. However, his renal
biopsy performed 1 day after the admission showed marked pathognomonic
characteristics. Not only did his glomeruli show class I lupus nephritis with
mesangial depositions of IgG, IgA, C3, and C1q, but also tubulointerstitial
nephritis with marked T-lymphocyte infiltration. These infiltrated T cells partly
had nuclear atypia. The patient was positive for human T cell leukemia virus type
1 (HTLV-1) antibodies. Furthermore, clonal rearrangements of T cell receptor
gamma chain gene was detected in the DNA extracted from his kidney sections by
the polymerase chain reaction (PCR) method. A second renal biopsy 6 months after
the prednisolone treatment showed that the infiltrating T lymphocytes had
markedly diminished. This is the first case report of lupus nephritis class I
with tubulointerstitial nephritis, which might include oncogenic T lymphocytes,
in an HTLV-1 positive patient.
PMID- 28509224
TI - Successful kidney transplantation for a dialysis patient with anthracycline
induced cardiomyopathy: a case report.
PMID- 28509225
TI - A case of membranoproliferative glomerulonephritis developed over twenty years
with three different findings of renal pathology.
AB - A 31-year-old woman with proteinuria, hypocomplementemia, rheumatoid factor, and
high serum polyclonal IgM concentration was admitted to our hospital for renal
biopsy. She had a past history of two renal biopsies. When she was 12 years old,
she developed proteinuria, microscopic hematuria, and hypocomplementemia. She was
diagnosed as having 'IgM nephropathy' based on minor glomerular abnormalities as
determined by light microscopy and IgM and C3 deposition in the mesangial region
by immunofluorescence microscopy at the first biopsy. Despite corticosteroid
treatment, her proteinuria did not improve and she discontinued regular
outpatient checkups. When she was 29 years old and pregnant, she developed
preeclampsia and, after delivery, a second renal biopsy was implemented. She was
diagnosed as having progressed 'IgM nephropathy' with endotheliosis induced by
preeclampsia. She was treated with angiotensin II receptor blocker and her
proteinuria diminished; however, 1 year after the delivery, she developed
proteinuria again, along with microscopic hematuria and hypocomplementemia. A
third renal biopsy was conducted at 31 years of age and she was diagnosed as
having membranoproliferative glomerulonephritis (MPGN) type I on the basis of
diffuse mesangial proliferation, endocapillary hypercellularity with double
contour of the capillary wall, and lobular formation in glomeruli, as determined
by light microscopy. Immunofluorescence staining demonstrated deposits of C3, C4,
C1q, and IgM in the mesangial region and capillary wall. She underwent
corticosteroid therapy followed by normalization of urinalysis and serum
complement level. Although she had initially been diagnosed with 'IgM
nephropathy', she was finally diagnosed with secondary MPGN and was successfully
treated by corticosteroid therapy.
PMID- 28509226
TI - Cytomegalovirus and Aspergillus spp. coinfection in organ transplantation: a case
report and review of the literature.
AB - With the advent of potent immunosuppressive options, acute rejection episodes
have decreased at the expense of increased incidence of opportunistic infections
in solid organ recipients. In the absence of any preventive therapy, 30-75 % of
transplant recipients develop cytomegalovirus (CMV) infection. Candida spp. and
Aspergillus spp. account for more than 80 % of invasive fungal infections in
solid organ recipients. This co-occurrence of two commonly seen opportunistic
infections may end up in fatality. Here, we present a case of concomitant
Aspergillus spp. and CMV infection and discuss the relevant literature. A 54-year
old male patient presented with fever, shortness of breath, and chest pain on the
9th posttransplant week after renal transplantation. CMV-DNA by polymerase chain
reaction (PCR) was 1,680,000 copies/ml, thus, valganciclovir dose was increased.
There were inspiratory crackles at both lung bases, and chest computed tomography
(CT) revealed multiple fungal balls throughout the right lung. Galactomannan
antigen was positive, and voriconazole and other antimicrobials were subsequently
added to the treatment. At the end of the therapy, on control CT, pneumonic
consolidation had disappeared, sputum cultures didn't show Aspergillus spp., and
CMV-DNA reduced to 700 copies/ml. The patient showed a favorable clinical
response to combined treatment; fever, dyspnea, and pleuritic chest pain
disappeared. Both CMV disease and aspergillosis may present as pulmonary disease;
thus, the characterization of one may not preclude the search for the other and
the timely initiation of treatment is of paramount importance for good outcomes.
PMID- 28509227
TI - A case of secondary focal segmental glomerulosclerosis associated with malignant
hypertension.
AB - Focal segmental glomerulosclerosis (FSGS) is associated with various
clinicopathological conditions, including hypertension. We report here a case of
secondary FSGS associated with malignant hypertension. A 33-year-old man with a 1
month history of visual impairment and headache visited the Department of
Ophthalmology at our hospital and was found to have hypertensive retinopathy and
severe hypertension (230/160 mmHg). He was referred to our department based on
suspected renal dysfunction. His blood pressure on admission was 250/130 mmHg.
Physical examination and laboratory tests revealed hypertensive cardiac
dysfunction, focal brain edema, renal dysfunction (serum creatinine, Cr 7.07
mg/dl, blood urea nitrogen, BUN 49.9 mg/dl), massive proteinuria (10.7 g/day),
and thrombotic microangiopathy. Funduscopy showed exudate, hemorrhage, and
papilledema. The cause of secondary hypertension could not be identified. He was
treated for primary malignant hypertension, but required hemodialysis 3 days
after admission due to anuria. Treatment with antihypertensive agents resulted in
the gradual recovery of renal function, although heavy proteinuria continued with
nephrotic syndrome. Renal biopsy performed 1 month after admission showed
features of malignant nephrosclerosis with secondary FSGS. Hemodialysis was
discontinued following further improvement in renal function and the most recent
laboratory tests showed proteinuria 1.8 g/day and persistent renal dysfunction
(BUN 36.5 mg/dl, Cr 3.14 mg/dl). Malignant hypertension may cause various
injuries, including glomerular endothelial and epithelial cell injuries in
glomerular hypertension and hyperfiltration, increase of the renin-angiotensin
aldosterone system, and endothelial-epithelial interaction, resulting in the
development of secondary FSGS and heavy proteinuria.
PMID- 28509228
TI - Renal transplantations from parents to siblings with autosomal recessive Alport
syndrome caused by a rearrangement in an intronic antisense Alu element in the
COL4A3 gene led to different outcomes.
AB - Two siblings with autosomal recessive Alport syndrome (ARAS) obtained renal
transplants from their consanguineous parents. Their COL4A3 mRNA transcripts were
disrupted by a 139 bp intronic sequence between exon 48 and 49, which was derived
from an antisense Alu element in this intron. The new amino acid sequence from
the cryptic exon was terminated by a stop codon at the 1511th codon, resulting in
the loss of 76 % alpha3(IV)NC1. This is the first case report of kidney
transplantations between ARAS-homozygous siblings and their heterozygous parents.
The brother experienced acute rejection just after transplantation and post
transplantation anti-glomerular basement membrane (GBM) nephritis, whereas the
sister has experienced no problems to date. The anti-GBM nephritis could have
resulted from the acute rejection. The COL4A3 gene heterozygous mutated parents,
who are possibly at risk for thin basement membrane disease, have maintained
their renal functions without urinary abnormalities after renal transplantation
to date.
PMID- 28509229
TI - Atypical sarcoidosis diagnosed by bone marrow biopsy during renal workup for
possible multiple myeloma.
AB - Sarcoidosis is a multi-organ disease of unknown etiology characterized by non
caseating granulomas. Here we report the case of a 78-year-old white male with a
past medical history of diabetes mellitus, hypertension, and chronic kidney
disease stage III with a baseline serum creatinine of 2.5 mg/dl. The patient had
a prior admission history for acute kidney injury (AKI) attributed to dehydration
and medication-induced nephro-toxicities. He presented to the renal clinic for
follow-up with acute worsening of chronic kidney failure with a serum creatinine
level of 3.5 mg/dl. Examination revealed that he was anemic and mildly
hypercalcemic with suppressed parathyroid hormone and had proteinuria of 1.3 g
per day. The computed tomography scan of the abdomen revealed right renal pelvic
non-obstructing calculi. Serum protein electrophoresis revealed gammopathy with
two distinct monoclonal peaks consisting of immunoglobulin G (IgG) kappa and IgG
lambda, respectively. The kappa/lambda ratio was within normal limits, and urine
protein electrophoresis showed no evidence of a monoclonal peak or Bence Jones
proteins. Further workup for multiple myeloma, including bone marrow (BM) biopsy,
revealed polyclonal plasma cells and B cells with no clonality. No morphological
and immune-phenotypic evidence of plasma cell dyscrasia was found, but BM biopsy
did show numerous non-caseating granulomas consistent with sarcoidosis. Skin
biopsy from non-scaly 6-mm skin colored papule also showed non-caseating
granulomas. The patient had elevated angiotensin-converting enzyme levels (165
ug/l) and an erythrocyte sedimentation rate of 27 mm/h. Kidney biopsy did not
show granulomas. The hypercalcemia, proteinuria, and AKI responded well after 2
weeks of 60 mg oral prednisone daily.
PMID- 28509230
TI - Methylprednisolone pulse therapy and intravenous cyclophosphamide therapy
combined with cocktail therapy in severe pediatric Henoch-Schonlein purpura
nephritis patient.
AB - Henoch-Schonlein purpura (HSP) is a common self-limited vasculitis in children.
The long-term prognosis depends on renal involvement. In severe Henoch-Schonlein
purpura nephritis (HSPN) patients, >50 % have crescent formation and nephrotic
syndrome that are important predicted outcomes. Therefore, for such patients, an
aggressive immunosuppressive therapy is needed to prevent the progression.
However, there is no consensus for an appropriate therapeutic regimen for severe
pediatric HSPN patients. In this paper, we have reported on a 6-year-old boy who
presented with HSPN with nephrotic syndrome and severe histopathological
abnormalities; he was diagnosed with International Study of Kidney Disease in
Children (ISKDC) grade IVb. Despite treatment with methylprednisolone pulse
therapy, followed by oral prednisolone and dipyridamole; the nephrotic syndrome
persisted. Subsequently, intravenous cyclophosphamide therapy (IVCY) (500-1,000
mg m-2 once a month for 7 months; total 6,000 mg m-2) was administered, followed
by azathioprine and enarapril. Within 7 months of disease onset, complete
remission was achieved. After 22 months of the initial renal biopsy, the second
biopsy was performed to confirm treatment efficacy. Histopathological findings
improved, and ISKDC grade IIIa was diagnosed. Even after 5 years of HSPN onset,
complete remission and normal renal function is maintained. Although our evidence
is restricted to single patient, we have shown that MPT and IVCY combined with
cocktail therapy may be an effective treatment for severe pediatric HSPN.
PMID- 28509231
TI - Two cases of eating disorder revealed by the breakout of acute kidney injury
after angiotensin II receptor blocker administration.
AB - Case 1: A 39-year-old woman with schizophrenia, obesity, hypertension and
dyslipidemia was admitted to our hospital for deteriorating serum Cr level, from
97.2 to 645.3 umol/l. She had been started on losartan 5 months earlier. After
suspension of losartan and infusion of saline, her serum Cr level gradually
recovered and she was discharged. Unfortunately, her physician restarted her on
losartan, and 5 months after this discharge, her serum Cr level rose again to
194.5 MUmol/l; again, serum Cr promptly recovered when losartan was discontinued.
Self-induced vomiting after overeating, suggesting bulimia nervosa, was revealed
via the detection of a remarkable reduction of chloride compared to sodium in her
spot-urine sample. Case 2: A 39-year-old woman who had been diagnosed with
bipolar disorder and diabetes mellitus was admitted to our hospital with
suspected diabetic ketoacidosis. After improvement in her blood sugar level,
olmesartan administration for hypertension was begun. Four days later, her serum
Cr level had risen from 60.1 to 256.4 MUmol/l. After suspension of olmesartan and
infusion of saline, her serum Cr level gradually fell to normal levels.
Urinalysis revealed the dissociation of sodium and chloride. During her
hospitalization, habitual self-induced vomiting was discovered. The measurement
of urinary electrolytes may be useful for the detection of eating disorders with
self-induced vomiting; in these patients, the administration of angiotensin II
receptor blockers may induce acute kidney injury.
PMID- 28509232
TI - A case of MPO- and PR3-ANCA-negative pauci-immune renal-limited small-vessel
vasculitis associated with endometrial neuroendocrine small cell carcinoma.
AB - A 69-year-old woman was admitted to our hospital for rapid increase in serum
creatinine level with microscopic hematuria and nephrotic-range proteinuria.
Three months prior to admission, she became aware of atypical genital bleeding,
leading her gynecologist to suspect endometrial cancer. Light microscopy
examination of renal biopsy revealed crescentic glomerulonephritis with
peritubular capillaritis. Immunofluorescence microscopic examination did not
detect any significant staining, and no electron-dense deposits were detected by
electron microscopy. No autoantibodies, including anti-myeloperoxidase- or anti
proteinase3-anti-neutrophil cytoplasmic antibodies were detected. The patient
underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy and
was found to have endometrial neuroendocrine small cell carcinoma (NSCC), stage
1B. In her clinical course, her serum creatinine level gradually improved without
immunosuppression therapy. Endometrial NSCC is a rare endometrial malignancy.
This is the first case report of vasculitis associated with NSCC originating from
the uterus.
PMID- 28509233
TI - Hyponatremia associated with demyelinating disease of the nervous system.
AB - A 63-year-old man was diagnosed with periodontitis and underwent tooth
extraction. Several days later, he suffered a high fever, ischuria, a change in
personality, and disorientation. A urologist examined him and found severe
hyponatremia (117 mEq/L), and he was then transferred to our hospital. On
admission, physical findings revealed dysfunction of the bladder and bowel,
altered mental status, and hypovolemia. Blood chemistry showed serum sodium of
120 mEq/L, a serum urate of 1.4 mg/dL, urinary Na of 61 mEq/L, and fractional
urate excretion of 16 %. Examination of the cerebrospinal fluid (CSF) showed
monocytosis. Magnetic resonance imaging (MRI) of the brain and spinal cord showed
multiple lesions characterized by hyperintensity on T2-weighted sequences,
suggesting demyelinating disease. His sodium concentration normalized 3 days
after volume replacement therapy, and his altered mental status along with the
dysfunction of the bladder and bowel were promptly improved after the initiation
of high-dose glucocorticoids. Additionally, the abnormal lesions on MRI markedly
decreased. This clinical course led to the likely diagnosis of acute disseminated
encephalomyelitis (ADEM). Hyponatremia in neurologically injured patients is
usually attributed to the syndrome of inappropriate antidiuretic hormone (SIADH)
or cerebral salt-wasting syndrome (CSWS). In the present patient, the uric acid
level remained low and uric acid excretion remained elevated despite correction
of the hyponatremia, which suggested CSWS. The differentiation of CSWS from SIADH
is difficult but critically important due to the fact that the disorders are
managed differently. Coexistence of ADEM and CSWS has rarely been reported.
PMID- 28509234
TI - Combined membranous nephropathy and crescentic glomerulonephritis with concurrent
anti-glomerular basement membrane antibody and myeloperoxidase-specific anti
neutrophil cytoplasmic antibody.
AB - We report a case of a 71-year-old man with rapidly progressive nephritic syndrome
and dual positivity for anti-glomerular basement membrane antibody and
myeloperoxidase-specific anti-neutrophil cytoplasmic antibody. Renal biopsy
revealed crescentic, mainly cellular, glomerulonephritis with granulomatous
lesions, and advanced membranous changes. Membranous nephropathy had apparently
existed for an extended period before the development of crescentic
glomerulonephritis. In some studies reporting the simultaneous occurrence of both
diseases, membranous nephropathy might be followed by crescentic
glomerulonephritis, presumably from a histological point of view. Although we
cannot prove a causal relationship between the two diseases, we caution that
precise observations, especially histological, are necessary in similar cases.
PMID- 28509236
TI - Renal cell neoplasm of oncocytosis: a type of unclassified renal cell carcinoma.
AB - A 69-year-old woman was referred to us because a cyst in the lower pole of the
left kidney had been pointed out on screening ultrasound. Computed tomography
(CT) demonstrated a mural nodule of the wall of the cyst with an enhancement
effect, suggesting cystic renal cell carcinoma (cT1aN0M0). The patient underwent
retroperitoneoscopic non-ischemic partial nephrectomy using a microwave tissue
coagulator. A hematoxylin-eosin-stained specimen showed that the wall of the
cystic tumor consisted of the proliferation of large cells with rich eosinophilic
granules in the cytoplasm and round-shaped nuclei, which were the characteristics
of oncocytoma. This was followed by immunohistochemical studies, because of
findings of local cell invasion, mitosis, and necrosis, suggesting malignancy.
The results were: CK7, strongly positive; PAX2, negative; colloidal iron stain,
negative; c-kit, weakly positive; vimentin, positive; and RCC marker, negative.
Thus, although the tumor showed characteristics of oncocytoma and/or chromophobe
renal cell carcinoma (pT1a), it could not be classified according to the known
categories: it should be designated as renal cell carcinoma (neoplasm) of
oncocytosis, a novel category of unclassified renal cell carcinomas. The present
case indicated the fact that renal cell carcinomas resembling oncocytoma
certainly exist.
PMID- 28509235
TI - Monitoring with serum SP-A, SP-D, and KL-6 in a patient with interstitial
pneumonia complicated with ANCA-associated glomerulonephritis.
AB - A 69-year-old woman was admitted to hospital, complaining of fatigue and dry
cough. Her renal function deteriorated rapidly, and the laboratory findings
showed elevated myeloperoxidase-specific anti-neutrophil cytoplasmic antibody
(ANCA). Renal biopsy examination revealed crescentic glomerulonephritis (pauci
immune type), and linear opacities and a honeycomb appearance in both lower lobes
was evident on the chest computed tomography scan. The patient was diagnosed as
having ANCA-associated glomerulonephritis complicated with mild interstitial
pneumonia (IP). Treatment with methylprednisolone pulse therapy improved both her
renal function and IP, but her lung lesions worsened during the course of
tapering the prednisolone doses. After careful observation, her IP improved
gradually without specific treatment. Worsening or improvement of her lung
lesions was accompanied by changes in the serological markers of IP, namely,
surfactant protein-A, surfactant protein-D, and KL-6. We found that monitoring
these markers was helpful in diagnosing and managing IP in our patient with ANCA
associated vasculitis.
PMID- 28509237
TI - Superior mesenteric artery syndrome due to duodenal edema in a chronic renal
failure patient: a case report.
AB - A 74-year-old woman had been treated conservatively for type 2 diabetes mellitus
(DM) and DM nephropathy since 2004. Her renal function gradually deteriorated,
and she developed chronic renal failure (CRF) with a serum creatinine level
between 2.5 and 3.0 mg/dl in 2010. She presented to our hospital with nausea and
vomiting related to the progression of CRF in May 2011. An abdominal computed
tomography (CT) scan showed distention of the upper digestive tract from the
stomach to the third portion of the duodenum, ascites, and compression of the
duodenum by the abdominal aortic artery and the overlying superior mesenteric
artery (SMA), which was caused by edema along the gastrointestinal tract, in
particular, at the duodenum. Therefore, she was diagnosed with SMA syndrome.
Decompression of the distended upper digestive tract was achieved using a
nasogastric tube, and hemodialysis was also initiated in order to adequately
control her fluid balance disorder, which was thought to have induced the
duodenal edema and ascites. After initiating these treatments, her condition
gradually improved, and she fully recovered after approximately 2 months of
treatment. Thus far, there has been no report of SMA syndrome caused by duodenal
edema associated with the progression of CRF that was successfully treated by
conservative treatment and the initiation of blood purification.
PMID- 28509238
TI - Membranous nephropathy associated with type 1 autoimmune pancreatitis and
dominant glomerular IgG4 deposit.
AB - We report a case of membranous nephropathy associated with type 1 autoimmune
pancreatitis. A 58-year-old man presented with anorexia. Work-up revealed a mass
in the pancreatic head, which was subsequently resected. Pathological examination
showed diffuse infiltration of immunoglobulin (Ig) G4-positive plasma cells,
which was compatible with the diagnosis of type 1 autoimmune pancreatitis. Serum
IgG4 was elevated. He developed nephrotic syndrome around the time of the
surgery. Kidney biopsy confirmed the diagnosis of membranous nephropathy.
Immunofluorescent staining showed predominant glomerular IgG4 deposit among IgG
subclasses. Tubulointerstitial nephritis, which is usually a dominant feature of
renal involvement in IgG4-related disease, was not observed. The patient was
treated with prednisolone and several immunosuppressants. During the course, the
degree of proteinuria was associated with the serum IgG4 level. Serum antibody
against phospholipase A2 receptor was negative. These findings together with IgG4
dominant glomerular deposit suggest that IgG4 may play a unique role in the
pathogenesis of secondary membranous nephropathy caused by IgG4-related diseases.
PMID- 28509240
TI - Cytokine dynamics in a 14-year-old girl with tubulointerstitial nephritis and
uveitis syndrome.
AB - Tubulointerstitial nephritis and uveitis (TINU) syndrome, which was first
described in 1975, has been reported in more than 130 patients, mostly in
adolescent or young women. Although data concerning the etiologic background of
this inflammatory disease are limited, several humoral factors, including
cytokines, have been reported in association with the disease. Here, we report a
case of TINU in a 14-year-old girl, whose renal and ophthalmological improvement
was associated with the decrease of serum levels of tumor necrosis factor-alpha
(TNF-alpha), interferon-gamma (IFN-gamma), and interleukin-8 (IL-8). This
suggests the presence of T-cell-mediated immunity in this unique syndrome.
PMID- 28509239
TI - An autopsy case that manifested no convincing histological changes of severe
renal failure after hematopoietic stem cell transplantation.
AB - A 48-year-old Japanese woman, who had been diagnosed with smoldering adult T-cell
leukemia, was admitted to our hospital for hematopoietic stem cell
transplantation (HSCT) because of an acute exacerbation of her disease. After
myeloablative conditioning procedures, comprising cytarabine with
cyclophosphamide and total body irradiation, the HLA-matched unrelated bone
marrow stem cells were infused (day 0). Her serum creatinine concentration,
having been 0.6 mg/dL at baseline, began to increase from day 1 and was 2.3 mg/L
on day 7. Hemodialysis was required to treat fluid overload and worsening uremia
on days 8 and 9. On day 10, she presented with refractory hypotension and died
due to multi-organ failure on day 12. Renal pathology at autopsy showed no
specific histological changes to which her clinically severe acute kidney injury
(AKI) was attributable. This case suggests that post-HSCT AKI is not necessarily
accompanied by apparent renal histologic damage, even if it is clinically
serious.
PMID- 28509242
TI - Endovascular treatment of renal artery stenosis improves contralateral renal
hypertrophy with nephrotic syndrome.
AB - Nephrotic syndrome due to renovascular hypertension is uncommon. We herein report
a case of nephrotic syndrome associated with unilateral atherosclerotic renal
artery stenosis. A 76-year-old woman who had been taking antihypertensive
medication for more than 15 years was referred to our hospital for treatment of
uncontrolled hypertension and massive proteinuria in the nephrotic range. An
abdominal bruit was heard, and laboratory findings showed high plasma renin
activity and hypokalemia. Renal computed tomography angiography showed severe
stenosis of the ostium of the right renal artery and an atrophic right kidney.
The left renal artery was normal and the left kidney was compensatorily enlarged.
After admission, we started treatment with an angiotensin II receptor blocker and
subsequently performed percutaneous transluminal renal angioplasty with renal
artery stent placement. As a result, her blood pressure became well controlled
and the massive proteinuria disappeared. In addition, her stenotic-side renal
atrophy was resolved, concomitant with an improvement in her renal function. The
contralateral renal hypertrophy was also resolved.
PMID- 28509241
TI - A case of encapsulating peritoneal sclerosis presented shortly after renal
transplantation.
AB - Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication of
peritoneal dialysis (PD), characterized by extensive intraperitoneal fibrosis and
encasement of bowel loops. It typically associates with long-term PD and
progressive loss of ultrafiltration. The management of EPS has evolved
substantially from the original report of this entity and now includes
immunosuppressive agents, antifibrotic agents, nutritional support, and surgical
intervention. Although the exact cause of this condition remains obscure and
despite the possible positive effect of immunosuppression on EPS, it has been
described in the post-transplant setting upon the discontinuation of PD. We
report such a case of a former PD patient who presented with EPS a month after
renal transplantation. This article will highlight the current views regarding
the management of post-transplant EPS and introduce the problem of long-term PD
patients on the deceased-donor transplant waiting list.
PMID- 28509243
TI - A case of immunoglobulin A nephropathy treated successfully with tonsillectomy
and steroid pulse therapy 20 years after onset.
AB - A 46-year-old male was found to have proteinuria on a routine medical examination
in 1985 at the age of 22 years and was diagnosed with immunoglobulin A (IgA)
nephropathy by renal biopsy. He regularly visited a hospital, but 3 years later
made the decision to stop. In 2000, his serum creatinine level was 1.3 mg/dl. His
renal function then deteriorated, with persistent proteinuria and hematuria,
following which he visited our hospital in December 2008. A further renal biopsy
was performed. Active and chronic IgA nephropathy was confirmed histologically,
with sclerosing lesions also being found. He was treated with three courses of
steroid pulse therapy in February and tonsillectomy in April 2009. During the
follow-up period at the outpatient clinic, results for proteinuria and hematuria
were negative, suggesting that progression of renal impairment had been
prevented. The efficacy of tonsillectomy plus steroid pulse therapy for early IgA
nephropathy has been demonstrated, and this treatment was effective in our
patient 20 years after the onset of the disease.
PMID- 28509244
TI - Pregnancy in 4 women with childhood-onset steroid-sensitive nephrotic syndrome.
AB - Four women with childhood-onset steroid-sensitive nephrotic syndrome (SSNS) had 5
pregnancies. Their age at onset of SSNS was between 4 and 10 years, and age at
pregnancy was between 21 and 31 years. Three patients with frequent relapsing
nephrotic syndrome (NS) continued to relapse after 20 years of age. Two of them
had relapses during 6-32 gestational weeks of pregnancy and were treated with
prednisolone (PSL) 10-45 mg/day. One patient delivered a normal baby on 2
pregnancies. Another developed superimposed preeclampsia and her infant showed
asymmetrical type of intrauterine growth restriction (IUGR). There was no relapse
during pregnancy in 2 patients, including 1 with frequent relapses, who had no
relapse over 5 years preceding the pregnancy. In all four patients, normal renal
function and complete remission were noted at the last follow-up. Their 5 infants
were well at 1-7 years of age. Although hypertension, growth failure of the
placenta, and IUGR of the baby may complicate the pregnancy, most pregnancies
with SSNS seem to result in normal birth, even when relapses occur during
pregnancy and are treated with PSL.
PMID- 28509245
TI - Gamma 1-heavy chain deposition disease accompanied by IgG kappa in serum, urine,
and bone marrow.
AB - A 32-year-old Japanese woman presented with hypertension, nephrotic syndrome,
microhematuria, and severe hypocomplementemia. Her serum creatinine concentration
increased from 1.46 mg/dL (129.0 MUmol/L) to 3.46 mg/dL (305.8 MUmol/L) over 1
month. Renal biopsy revealed Congo red-negative nodular glomerulosclerosis
accompanied by mesangial proliferation. There was extensive staining of
immunoglobulin (Ig) G in the glomerular and tubular basement membranes and
expanded mesangial regions. Staining was negative for IgA, IgM, and kappa and
lambda light chains and positive for the gamma 1 IgG subclass. Staining for
constant domains of the gamma heavy chains showed a deletion of the first
constant domain (CH1). Electron microscopy revealed electron-dense deposits in
the glomerular and tubular basement membranes and mesangium. These findings
indicated gamma 1-heavy chain deposition disease (HCDD). Serum and urine
immunoelectrophoresis revealed an IgG kappa monoclonal band, whereas bone marrow
biopsy revealed monoclonal plasmacytosis with positive staining for kappa chains.
HCDD associated with kappa light chain is extremely rare. We report the first
case of HCDD with IgG kappa detected in the serum, urine, and bone marrow.
PMID- 28509246
TI - Garland-pattern postinfectious glomerulonephritis with IgA-dominant deposition.
AB - A histological subtype of acute postinfectious glomerulonephritis (APIGN), the
garland pattern, is identified not only by characteristic histological findings,
but also by severe clinical course as compared with typical APIGN. However, since
the morbidity of APIGN has decreased globally, there have been few reports on
this disease form in developed countries during the last two decades. Herein, we
report a case of adolescent garland-pattern APIGN with IgA-dominant deposits,
presenting with severe nephrotic syndrome and protracted hematuria and
proteinuria. We also review the clinical and histological features of 13
previously reported cases in Japan and compare them with our present case. In our
review, we confirmed IgA deposition in at least three of these patients, in whom
urinary protein excretion tended to be greater than those patients without IgA.
Greater awareness of this condition is necessary to ensure appropriate follow-up
of the clinical course of patients with garland-pattern APIGN with IgA
deposition.
PMID- 28509247
TI - Successful treatment of bortezomib-refractory multiple myeloma derived from
monoclonal gammopathy of undetermined significance with dose-adjusted
lenalidomide therapy in a patient with concomitant end-stage renal disease due to
diabetic nephropathy requiring haemodialysis.
AB - Malignancy is a fatal complication of end-stage renal disease (ESRD) requiring
haemodialysis. However, the successful treatment of haematological malignancies
has been rarely reported. We describe the case of a 63-year-old man who presented
with IgA-type multiple myeloma (MM; Durie-Salmon stage IIIB) derived from
monoclonal gammopathy of undetermined significance concomitant with ESRD due to
diabetic nephropathy. First, haemodialysis was initiated before chemotherapy, and
bortezomib and dexamethasone were found to be ineffective. Subsequently, 8
courses of dose-adjusted lenalidomide therapy were administered according to the
degree of haematological and renal functions. The patient remained in partial
remission without disease progression for 21 months. Thus, lenalidomide therapy
is effective for bortezomib-refractory MM concomitant with ESRD.
PMID- 28509248
TI - Periodic hypokalemia associated with cyclic Cushing's syndrome.
AB - A 69-year-old woman presented with periodic hypertension, edema, and hypokalemia
that occurred within an interval of a few weeks. Her laboratory test values
showed autonomously elevated plasma adrenocorticotropic hormone (ACTH) and
cortisol concentrations. The patient's Cushingoid features were not evident on
first admission. Several weeks later, in spite of constant oral potassium
supplementation, severe hypokalemia recurred with Cushingoid features and
worsening symptoms of leg edema and pigmentation, which spontaneously disappeared
within a few days. Her periodic symptoms occurred in parallel with fluctuations
of plasma ACTH and cortisol concentrations. A series of endocrinological and
pituitary imaging findings led to a tentative diagnosis of cyclic Cushing's
syndrome caused by ectopic ACTH secretion. However, chest and abdominal computed
tomography did not reveal any candidate lesion. The patient's periodic
hypercortisolemia and symptoms were well controlled after treatment with
metyrapone plus dexamethasone. This is a very rare case of periodic hypokalemia
and hypertension caused by cyclic Cushing's syndrome.
PMID- 28509249
TI - Renal cell carcinoma presenting as AA amyloidosis: a case report and review of
the literature.
AB - A 47-year-old Caucasian man developed mild diarrhoea associated with more than 10
kg weight loss, severe fatigue and anaemia. Endoscopy demonstrated deposits of AA
amyloid within the gastrointestinal tract. He had heavy proteinuria with a serum
albumin of 15 g/L consistent with systemic AA amyloidosis. He had no symptoms to
suggest an underlying chronic inflammatory condition but had CRP 130 mg/L and SAA
474 mg/L. In an attempt to identify the source of his inflammatory response, he
underwent a contrast-enhanced whole-body computed tomography scan, which revealed
a necrotising mass lesion in the right kidney consistent with a renal cell
carcinoma. It also showed non-mechanical obstruction of the small bowel and,
immediately post-imaging, the patient developed intractable vomiting followed by
oliguric renal failure requiring haemodialysis. Despite his renal and gut
failure, he underwent right radical nephrectomy without further complications.
Histology showed complete resection of a clear cell renal cell carcinoma and
renal amyloid deposits. Post-surgery, his acute-phase response decreased to
normal, consistent with the renal cell carcinoma acting as the inflammatory
stimulus. Although he remains dialysis dependent, his gut function improved and
he has regained both normal weight and serum albumin. Our case demonstrates
partial resolution of AA amyloidosis with removal of the inflammatory source.
PMID- 28509251
TI - Increased antiangiogenetic factors in severe proteinuria without hypertension in
pregnancy: is kidney biopsy necessary?
AB - Acute onset of severe proteinuria during pregnancy obliges physicians to
clinically discriminate between gestational proteinuria (GP) and new onset of
nephritis. A multiparous woman developed severe proteinuria (5.8 g/day) without
hypertension at 32 weeks of gestation. We measured the maternal level of soluble
fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng), which were
extremely high (41.3 and 54.8 ng/ml, respectively), leading us to consider this
condition as GP rather than acute onset of nephritis. Thus, we did not perform a
kidney biopsy and did not administer a steroid agent. Non-reassuring fetal status
required emergency Cesarean section at 33 weeks. Proteinuria decreased to 0.36
g/day at 12 weeks after delivery, and finally disappeared 26 weeks postpartum.
Measurement of sFlt-1 and sEng in a pregnant woman with severe proteinuria
without hypertension may assist in differential diagnosis of GP from acute onset
of nephritis, and thus help to decide whether to perform kidney biopsy during
pregnancy.
PMID- 28509250
TI - Prerenal uremia induced by severe diarrhea due to colon adenoma: a case of
McKittrick-Wheelock syndrome in an elderly patient.
AB - McKittrick-Wheelock syndrome can be successfully treated by emergent dialysis,
prescription of bicarbonate, and endoscopic submucosal dissection, which allow
elderly people suffering from this syndrome to maintain their activities of daily
living. In patients with this syndrome, a large colonic villous adenoma secretes
excessive amounts of mucus and causes severe electrolyte depletion and
dehydration. An 81-year-old man who had been suffering from chronic renal failure
(creatinine 256.4 MUmol/L), hypertension, and arrhythmia presented with frequent
mucous diarrhea for a month. He was hospitalized for appetite loss, vomiting,
general fatigue, and acute renal failure. His blood tests and blood gas analysis
revealed urea nitrogen 58.9 mmol/L, creatinine 954.7 MUmol/L, pH 7.13, and a base
excess of -20.1 mmol/L. Although his symptoms were improved by the emergent
dialysis and rehydration, he suffered a relapse only 4 days after he was
discharged. At the second admission, a near-circumferential tumor was found in
the rectum by the colonoscopy, which was pathologically confirmed as a villous
adenoma. Considering his age and complications, endoscopic submucosal dissection
was selected, and internal use of sodium bicarbonate was prescribed. Diarrhea and
appetite loss were improved by these treatments, and the creatinine level was
also improved to 168.0 MUmol/L.
PMID- 28509252
TI - Renal vein thrombosis associated with oral contraception and smoking: a case
report from Japan, with literature review.
AB - Renal vein thrombosis, one of the common thrombotic complications of nephrotic
syndrome or renal cell carcinoma, is reportedly a rare complication of hormonal
contraception. Solitary renal vein thrombosis in the Japanese population is
thought to be very rare because the incidence of venous thromboembolism is
comparatively very low in Asian populations. We report a 38-year-old Japanese
female with left renal vein thrombosis associated with oral contraception and
concurrent smoking as the first Japanese case of solitary renal vein thrombosis
associated with oral contraceptives, with a review of the literature. Seven cases
were previously reported. The results revealed that all patients complained of
acute onset of pain around the involved kidney without urinary symptoms or fever,
and were effectively treated with anticoagulants. Other remarkable facts include
that nausea and vomiting were frequently seen, and that the renal outcome was
benign, despite various initial urine abnormalities. This report may alert
clinicians to the importance of these risk factors as an etiology of renal vein
thrombosis even in Asian populations. Clinicians should regard renal vein
thrombosis as one of the differential diagnoses for acute flank pain in patients
using oral contraceptives. A detailed history taking that reveals oral
contraception, smoking, and other thrombophilic predispositions as well as timely
computed tomographic scans would be the keys to diagnosis. Smoking cessation
should be strongly recommended to oral contraceptive users, especially women over
35 years of age, regardless of dosage.
PMID- 28509253
TI - Membranous nephropathy secondary to Graves' disease with deposits of thyroid
peroxidase in an adult.
AB - A 40-year-old woman was diagnosed with Graves' disease in 2001 and treated with
thiamazole, but disease control was poor. She was referred to our hospital in
2011 for exacerbation of proteinuria, which had been present since 2006.
Urinalysis showed a protein/creatinine ratio of 4.2 g/gCre and microhematuria,
and a renal biopsy was performed. On electron microscopy, high electron density
deposits were seen on the epithelial side of the glomerular basement membrane.
IgG was also deposited along the glomerular loop wall, and membranous nephropathy
was diagnosed. Immunostaining revealed thyroid peroxidase deposits but not
thyroglobulin antigen deposits, suggesting that the membranous nephropathy was
secondary to Graves' disease. The membranous nephropathy improved with 131I
treatment. To our knowledge, this is the first adult case of membranous
nephropathy originating from Graves' disease in which deposits of thyroid
peroxidase antigens have been detected.
PMID- 28509254
TI - Effect of eculizumab and recombinant human soluble thrombomodulin combination
therapy in a 7-year-old girl with atypical hemolytic uremic syndrome due to anti
factor H autoantibodies.
AB - Atypical hemolytic uremic syndrome (aHUS), which is defined as non-Shiga toxin
associated hemolytic uremic syndrome, is a type of thrombotic microangiopathy.
This syndrome presents with hemolytic anemia, thrombocytopenia, and acute kidney
injury. Excessive complement activation due to genetic disorders of the
complement system or production of autoantibodies to factor H (FH) causes the
disease. We report a successful treatment course using eculizumab and recombinant
human soluble thrombomodulin (rTMD) for a 7-year-old girl with aHUS due to anti
FH autoantibodies. Although her chief complaints were abdominal pain and loose
stools, we were finally able to diagnose her with aHUS because Shiga toxin
producing Escherichia coli was not detected in her feces and a hemolytic assay
analyzing FH function was positive. We administrated rTMD to our patient because
of signs of disseminated intravascular coagulation. Soon after the therapeutic
intervention, the platelet count began to increase and abdominal pain was
moderately improved. Plasma exchange limited the efficacy of her disease.
Therefore, we administered eculizumab, monoclonal humanized antibody against C5,
3 weeks after admission. Platelet counts immediately increased and kidney
function gradually recovered. Genetic disorders were not detected. However, anti
FH autoantibody was observed. There were no symptoms for recurrence of aHUS or
kidney dysfunction for 15 months, as a result of the administration of eculizumab
every other week. In conclusion, combination therapy of eculizumab and rTMD was
effective for an aHUS patient. This therapy may be helpful for improving the
prognosis and long-term kidney function of aHUS patients.
PMID- 28509255
TI - Five cases of tonsillectomy and steroid pulse therapy for recurrent
immunoglobulin A nephropathy after kidney transplantation.
AB - Five cases of recurrent immunoglobulin A nephropathy (IgAN) after kidney
transplantation were successfully treated by tonsillectomy and steroid pulse
therapy (SPT). The clinical background and pathology in the five cases were
different, but good results were obtained in all of them. In cases 1 and 2, mild
recurrent IgAN developed and failed to remit after tonsillectomy alone, but a
remission was achieved in both cases after SPT. In case 3, highly active
recurrent IgAN with crescent lesions developed 13 years after kidney
transplantation, and a remission was achieved after SPT. In case 4, renal biopsy
specimens showed pathological findings of recurrent IgAN with tubulitis, and
hematuria and proteinuria resolved after SPT. In case 5, the biopsy findings
indicated recurrent IgAN with chronic rejection. Tonsillectomy was followed by
resolution of the proteinuria, and a remission was achieved after SPT. In
conclusion, SPT is effective in inducing a remission of recurrent IgAN when
tonsillectomy alone fails.
PMID- 28509256
TI - Long-term prognosis of 4 children with steroid-sensitive nephrotic syndrome and
relapse after 30 years of age.
AB - Some children with steroid-sensitive nephrotic syndrome (SSNS) have been reported
to suffer relapses in adulthood, but the clinical course of such adults is
unclear. Four children with SSNS suffered relapses after 30 years of age. Those 4
patients developed frequently relapsing nephrotic syndrome (NS) between 2 and 10
years of age. They were treated with prednisolone (PSL) combined with
cyclophosphamide in 3 patients, mizoribine in 2, and cyclosporine in 1 during
childhood, and with cyclosporine in 2 during adulthood. After 20 years of age,
the frequency of relapses gradually decreased. The last relapse occurred between
33 and 39 years of age, and proteinuria disappeared within 1 month after the
start of treatment with PSL. At the last follow-up, all 4 patients continued to
receive PSL, had normal renal function, and were in complete remission of NS when
they were between 33 and 41 years of age. Although the long-term outcome of SSNS
is usually considered to be favorable, pediatricians should be aware that some
children with SSNS may require long-term treatment during adulthood.
PMID- 28509257
TI - A case of antiglomerular basement membrane glomerulonephritis complicated by
membranous nephropathy.
AB - The sequential or simultaneous presentation of anti-glomerular basement membrane
(anti-GBM) glomerulonephritis with membranous nephropathy (MN) has been
infrequently reported. Although the mechanism underlying MN superimposed on anti
GBM glomerulonephritis is unknown, the two entities are believed to be
interrelated. We report the case of a 75-year-old woman diagnosed with rapidly
progressive glomerulonephritis. Renal biopsy revealed crescentic
glomerulonephritis with linear and granular staining of immunofluorescent IgG1
and IgG4 granular staining on the capillary loops. Electron microscopy revealed
extensive subepithelial deposits. These findings suggested simultaneous
development of anti-GBM glomerulonephritis and MN in this case. Serum
phospholipase A2 receptor (PLA2R) antibody was negative. The patient was treated
with prednisolone and plasma exchange, resulting in resolution of renal
insufficiency and a decrease in urinary protein. The rapid decrease in urinary
protein and absence of PLA2R antibody suggest that the mechanism of MN associated
with anti-GBM glomerulonephritis differs from that of primary MN.
PMID- 28509258
TI - AP-VAS 2012 case report: an atypical case of microscopic polyangiitis presenting
with acute tubulointerstitial nephritis without glomerular change.
AB - Renal involvement in myeloperoxidase-antineutrophil cytoplasmic antibody (MPO
ANCA)-associated vasculitis is frequently characterized by focal segmental
crescentic and/or necrotizing glomerulonephritis. However, a few cases of only
tubulointerstitial nephritis (TIN) involvement without any apparent glomerular
lesions have been reported. Here we report just such a case. A 74-year-old woman
was admitted to a nearby hospital with a 2-week history of pitting edema, fever
and anemia. She developed acute renal failure without proteinuria and microscopic
hematuria. The urinary excretion of N-acetyl-beta-D-glucosaminidase and beta2
microglobulin concentration were 30.3 U/ml and 42270 MUg/ml, respectively.
Gallium-67 scintigraphy revealed abnormal concentrations on both sides of her
kidneys. Her MPO-ANCA titer was 92 EU (normal range <10 EU). Skin and renal
biopsies demonstrated fibrinoid vasculitis, necrotizing angiitis and TIN without
glomerular change. Microscopic polyangiitis was diagnosed based on clinical and
pathological criteria. No other factor that could induce TIN was detected. This
case illustrates an unusual renal presentation of acute renal failure due to
necrotizing arteritis and TIN, consistent with MPO-ANCA-associated vasculitis
lacking crescentic glomerulonephritis. The pathogenesis is currently unclear, but
the low-affinity type of MPO-ANCA was identified.
PMID- 28509259
TI - Moran-type bounds for the fixation probability in a frequency-dependent Wright
Fisher model.
AB - We study stochastic evolutionary game dynamics in a population of finite size.
Individuals in the population are divided into two dynamically evolving groups.
The structure of the population is formally described by a Wright-Fisher type
Markov chain with a frequency dependent fitness. In a strong selection regime
that favors one of the two groups, we obtain qualitatively matching lower and
upper bounds for the fixation probability of the advantageous population. In the
infinite population limit we obtain an exact result showing that a single
advantageous mutant can invade an infinite population with a positive
probability. We also give asymptotically sharp bounds for the fixation time
distribution.
PMID- 28509261
TI - Management of fracture dorso-lumbar spine in a pregnant female by surgery in
prone position.
AB - Surgical management of thoraco-lumbar spine fracture in pregnancy has specific
concerns during surgery like positioning, approach, and radiation exposure to
fetus. We report a case of burst fracture of 12th thoracic vertebrae with
paraplegia in a young female with 26 weeks of gestation. Surgery was performed in
prone position on a Toronto frame. This report also discusses the management of
thoraco-lumbar spine fracture in pregnancy with review of literature.
PMID- 28509260
TI - Rapid Serum-Free Isolation of Oligodendrocyte Progenitor Cells from Adult Rat
Spinal Cord.
AB - Oligodendrocyte progenitor cells (OPCs) play a pivotal role in both health and
disease within the central nervous system, with oligodendrocytes, arising from
resident OPCs, being the main myelinating cell type. Disruption in OPC numbers
can lead to various deleterious health defects. Numerous studies have described
techniques for isolating OPCs to obtain a better understanding of this cell type
and to open doors for potential treatments of injury and disease. However, the
techniques used in the majority of these studies involve several steps and are
time consuming, with current culture protocols using serum and embryonic or
postnatal cortical tissue as a source of isolation. We present a primary culture
method for the direct isolation of functional adult rat OPCs, identified by
neuron-glial antigen 2 (NG2) and platelet derived growth factor receptor alpha
(PDGFralpha) expression, which can be obtained from the adult spinal cord. Our
method uses a simple serum-free cocktail of 3 growth factors - FGF2, PDGFAA, and
IGF-I, to expand adult rat OPCs in vitro to 96% purity. Cultured cells can be
expanded for at least 10 passages with very little manipulation and without
losing their phenotypic progenitor cell properties, as shown by
immunocytochemistry and RT-PCR. Cultured adult rat OPCs also maintain their
ability to differentiate into GalC positive cells when incubated with factors
known to stimulate their differentiation. This new isolation method provides a
new source of easily accessible adult stem cells and a powerful tool for their
expansion in vitro for studies aimed at central nervous system repair.
PMID- 28509262
TI - A case of cryopyrin-associated periodic syndrome with kidney transplant failure.
AB - The cryopyrin-associated periodic syndrome (CAPS) is an autosomal dominant
autoinflammatory disease characterized by fever, skin rash, and joint involvement
with acute inflammatory response. The genetic defect involves the NLRP3 gene that
encodes cryopyrin and leads to an abnormal production of interleukin-1 (IL-1).
Therefore, anti-IL-1 treatment represents an effective therapy. One of the most
severe manifestations of the disease is secondary amyloidosis that causes renal
failure. We present a patient with CAPS who underwent renal transplantation for
renal insufficiency caused by amyloidosis. The function of the transplanted
kidney deteriorated because of the late administration of IL-1 receptor
antagonist, anakinra. This case may indicate the importance of early initiation
of anti-IL-1 treatment in CAPS patients who have undergone kidney
transplantation.
PMID- 28509263
TI - Atopic dermatitis, cyclosporine, and nephrotoxicity.
PMID- 28509264
TI - A case of membranoproliferative glomerulonephritis and AA amyloidosis complicated
with pulmonary nontuberculous mycobacterial infection.
AB - A 75-year-old man was diagnosed with pulmonary nontuberculous mycobacterial (NTM)
infection in February 2005 and was treated with rifampicin, ethambutol, and
clarithromycin. However, the infection was resistant to treatment, and his chest
radiograph showed an abnormality that gradually seemed to aggravate. The
patient's sputum was positive for Mycobacteria. Moreover, the patient had dyspnea
and an underlying chronic inflammation in the lungs. He visited our hospital
because of dyspnea and leg edema in June 2011. Laboratory evaluation on admission
revealed proteinuria (6 g/day) and decreased serum total protein (5.8 g/dL) and
albumin (1.6 g/dL) levels, indicating nephrotic syndrome. Percutaneous renal
biopsy revealed membranoproliferative glomerulonephritis (MPGN) in the acute
stage and AA amyloidosis of mild degree. AA amyloidosis was also diagnosed
histologically on gastric and colonic biopsy, in addition to renal biopsy. His
renal function decreased gradually, and therefore, he underwent hemodialysis
therapy in January 2012. However, his gastrointestinal-related symptoms
persisted, and his appetite diminished, because of which he had become severely
malnourished; he died 8 months later. This is a rare case of a patient with two
different renal lesions (MPGN and AA amyloidosis) complicated with NTM. Our case
suggests that MPGN and amyloidosis should be considered in elderly patients with
nephrotic syndrome onset and chronic inflammation.
PMID- 28509265
TI - Hepatitis C virus-related glomerulonephritis with acute kidney injury requiring
hemodialysis that improved with virus removal and eradication using double
filtration plasmapheresis without interferon.
AB - A 66-year-old, hepatitis C virus (HCV)-positive woman was admitted to our
hospital with oliguria, systemic edema, and rapid deterioration of renal
function. Laboratory examination showed increased serum creatinine and decreased
serum albumin levels, complement activity, and cryoglobulin positivity. The HCV
RNA genotype was found to be 1b, and the viral load was high. Kidney biopsy
examination showed type I membranoproliferative glomerulonephritis with capillary
deposition of IgM and C3, indicating HCV-related glomerulonephritis. After
hospitalization, hemodialysis was immediately required because of uremia and
oliguria. Her renal function did not improve despite corticosteroid therapy. To
treat the increasing HCV load, virus removal and eradication by double-filtration
plasmapheresis therapy without interferon was performed, since the patient was
allergic to interferon therapy. This treatment improved renal function and
allowed the withdrawal from hemodialysis. This report presents a case of
successful VRAD without interferon therapy in a patient with HCV-related
glomerulonephritis and acute kidney injury that required hemodialysis.
PMID- 28509266
TI - A case of gefitinib-associated membranous nephropathy in treatment for pulmonary
adenocarcinoma.
AB - We experienced a case that was considered as gefitinib-associated membranous
nephropathy (MGN) in treatment for pulmonary adenocarcinoma. A female patient
aged 80 who had been treated for lung cancer was referred and hospitalized at our
hospital, because of nephrotic syndrome. The patient had pulmonary adenocarcinoma
(cT4N2M1a) with positive for epidermal growth factor receptor (EGFR) mutation.
Gefitinib, EGFR tyrosine kinase inhibitor, was initiated from 1 year and 2 months
ago. At that time, proteinuria was negative. The treatment effect on lung cancer
was so favorable that partial response had been maintained. However, from 4
months ago, edema of legs appeared, leading to become nephrotic syndrome. Renal
biopsy was performed, and secondary MGN was diagnosed, because of deposition of
peripheral IgG, mesangial IgA, and C3, as well as the deposition of peripheral
IgG4, IgG1, IgG2, and weak IgG3. We considered drug-induced MGN and discontinued
the administration of gefitinib. Subsequently, the proteinuria tended to decrease
gradually and became negative 10 months later. However, the lung cancer recurred
3 months after discontinuation of gefitinib and another molecular target drug,
erlotinib, was administered. At present, 13 months after discontinuation of
gefitinib, absence of proteinuria is maintained. It has been generally considered
that secondary MGN can be induced by both malignant tumor and their treatment. In
the present case, the clinical course and pathological characteristics showed the
secondary MGN that might be associated with gefitinib during the treatment for
pulmonary adenocarcinoma. The present case, to our knowledge, may be a first case
of gefitinib-associated MGN.
PMID- 28509267
TI - A hospital-acquired outbreak of catheter-related nontuberculous mycobacterial
infection in children on peritoneal dialysis.
AB - Catheter-related nontuberculous mycobacterial infection in children with chronic
renal failure on peritoneal dialysis (PD) is rare. However, there have been five
such infections in infants among PD patients at our center. Although the patients
were treated with antibiotics to which the organisms showed in vitro sensitivity,
they were clinically drug resistant. Hence, all PD catheters needed to be
removed. Thereafter, following hemodialysis treatment for approximately 1 month,
the PD catheters were replaced, with no recurrence of infection. On investigation
of the infection route, it was found that these bacteria had colonized around a
shower head in one of the bathrooms. These findings suggest that, in cases where
hot water systems at hospitals are considered at a high risk, frequent
sterilization is needed, especially around the shower heads. It is also necessary
to reconsider current standard practices in the management of catheter exit
sites, especially if the national incidence of infection increases.
PMID- 28509268
TI - Pulmonary hemorrhage associated with Henoch-Schoenlein purpura in an adult
patient primary diagnosed of IgA nephropathy.
AB - We describe a case of IgA nephropathy (IgAN) followed by pulmonary hemorrhage
associated with Henoch-Schoenlein purpura (HSP) in an adult female. The patient
had a history of renal insufficiency and persistent hematuria and proteinuria,
without any extra-renal involvement. She was diagnosed with IgAN 7 years before
the onset of HSP and had received immunosuppressive therapy for 6 years. One year
after discontinuing oral prednisolone and mizoribine, she suffered a pulmonary
hemorrhage. She presented with exacerbated urinary findings, and palpable
purpura, resulting in the diagnosis of HSP. Intravenous pulse methylprednisolone
followed by oral prednisolone (1 mg/kg/day) and a monthly intravenous
cyclophosphamide pulse resolved the pulmonary hemorrhage. In a review of 36 HSP
patients complicated with pulmonary hemorrhage, 27.8 % of the patients perished
[Rajagopala et al., Semin Arthritis Rheum 42:391-400, 1]. While the most
efficient therapeutic strategies for these patients have yet to be determined, we
speculate that an aggressive therapy of pulse methylprednisolone combined with
immunosuppression agents is likely to bring about the best outcome in cases with
pathological conditions similar to our patient's. On the other hand,
discontinuance of immunosuppressive therapy might have resulted in the
aggravation of the disease, hence we should examine patients carefully not to
miss the cue.
PMID- 28509269
TI - De novo myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-associated
glomerulonephritis 31 years after living-donor kidney transplantation.
AB - A 61-year-old woman was admitted to our hospital because of an unexpected rise in
serum creatinine (sCr) level with proteinuria and microhematuria. She had
undergone living-donor kidney transplantation 31 years before for end-stage renal
disease caused by chronic glomerulonephritis (GN). On admission, her sCr was 1.27
mg/dL which was increased from 0.6 mg/dL, urinary protein/creatinine ratio was
1.39 g/gCr, and urinary red blood cell count was more than 100 per high power
field. The allograft biopsy revealed crescentic glomerulonephritis with moderate
to severe tubulointerstitial inflammation. Immunofluorescence staining yielded
only a minimal staining for immunoglobulin A, and negative C4d in peritubular
capillary. Since increased myeloperoxidase-antineutrophil cytoplasmic antibody
(MPO-ANCA) titer of 45.5 U/mL was detected, we made the diagnosis of post
transplant MPO-ANCA-associated GN. She was treated with three doses of bolus
methylprednisolone (500 mg) followed by oral prednisolone therapy. Her sCr was
stable at 1.20 mg/dL thereafter. ANCA-associated GN should be considered in older
kidney transplant patients with new-onset urinary abnormalities because typical
systemic symptoms and vasculitis in other organs might be masked by maintenance
immunosuppression.
PMID- 28509270
TI - Uterus didelphys with obstructed hemivagina and contralateral multicystic
dysplastic kidney.
AB - Mullerian anomalies are often associated with urinary tract anomalies. Herlyn
Werner-Wunderlich syndrome or obstructed hemivagina and ipsilateral renal anomaly
are rare Mullerian anomaly comprising uterine didelphys, obstructed hemivagina,
and ipsilateral renal anomaly. We report an unusual case of uterus didelphys with
obstructed hemivagina and contralateral (not ipsilateral) multicystic dysplastic
kidney. An early diagnosis is critical to prevent complications such as adhesions
with subsequent infertility. A careful evaluation of the female reproductive
tract may be necessary in children with not only renal aplasia but also lateral
renal anomalies such as multicystic dysplastic kidney.
PMID- 28509271
TI - Preeclampsia before 20 weeks of gestation: a case report and review of the
literature.
AB - The occurrence of preeclampsia before 20 weeks of gestation is rare and usually
associated with trophoblastic diseases or antiphospholipid syndrome. Here, we
report a case of preeclampsia before 20 weeks of gestation in the absence of the
aforementioned disorders. A healthy 30-year-old nulliparous woman presented with
new onset of hypertension and proteinuria at 18 weeks of gestation. Fetal
ultrasound did not reveal any abnormalities. Empirical steroid treatment was
initiated based on a tentative diagnosis of underlying renal disease. The
clinical course of the disease was progressive despite steroid treatment and the
fetus died in utero 8 days after the initiation of treatment. Following delivery,
a renal biopsy was performed and provided a diagnosis of preeclampsia. All
symptoms resolved postpartum. This report demonstrates that preeclampsia may
occur before 20 weeks of gestation and should always be considered in the
differential diagnosis of pregnant women with new onset of hypertension with
proteinuria. Previous published cases are summarized briefly.
PMID- 28509272
TI - An unusual association between focal segmental sclerosis and lupus nephritis: a
distinct concept from lupus podocytopathy?
AB - Lupus nephritis (LN) is usually associated with immune deposition in the
glomerular capillary wall. On the other hand, focal segmental glomerulosclerosis
(FSGS) is not typically associated with immune deposition, and its pathogenesis
includes podocyte damage and loss. The definition of lupus podocytopathy (LP)
excludes patients with electron-dense glomerular basement membrane deposits.
Here, we report the case of an LN patient with nephrotic proteinuria. Renal
pathology demonstrated focal endocapillary hypercellularity superimposed on foam
cells. Immunofluorescence revealed diffuse global subepithelial immune deposits,
and electron microscopy showed electron-dense glomerular basement membrane
deposits and diffuse foot process effacement. Treatment with steroid and
cyclosporine improved her proteinuria. Post-treatment renal re-biopsy revealed
focal segmental sclerotic lesions closely resembling FSGS. These results indicate
that the pathogenesis of this case may involve an FSGS-like condition or
podocytopathic change. It is possible that careful examination would reveal
podocytopathic changes other than LP in patients previously diagnosed as LN class
III + V. Further investigations are needed to understand FSGS-like pathological
changes accompanied with capillary immune deposits in LN.
PMID- 28509273
TI - Post-infectious acute glomerulonephritis with vasculitis and pulmonary
hemorrhage.
AB - An 84-year-old male complained of fever, cough, sputum, and appetite loss. His
renal function rapidly worsened, and he had hypoalbuminemia and
hypocomplementemia. His condition worsened and C-reactive protein levels were
elevated. Vasculitis syndrome was suspected and he was administered 40 mg of
prednisolone, although myeloperoxidase antineutrophil cytoplasmic antibody
(ANCA), proteinase-3 ANCA and antiglomerular basement membrane antibody tests
were negative. His body temperature decreased and fatigue promptly resumed. On
renal biopsy, light microscopy revealed endocapillary and extracapillary
glomerulonephritis. Vasculitis was detected in interlobular arteries.
Immunofluorescence studies revealed granular deposits of C3 and IgG along
capillary walls. Electron microscopy revealed dome-shaped small electron-dense
granular subepithelial deposits. Acute post-infectious glomerulonephritis was
suspected. Although his renal function improved, he developed hemoptysis and was
diagnosed with pulmonary hemorrhage. He received methylprednisolone and plasma
exchange, and his respiratory status improved gradually. This is an extremely
rare case and suggests the importance of considering a differential diagnosis.
PMID- 28509274
TI - Lymphoproliferative disease-related mixed cryoglobulinemia treated with rituximab
and prednisolone.
AB - Mixed cryoglobulinemia is often associated with hepatic C virus infection and is
less common with hepatitis B virus infection, and it often progresses into
lymphoproliferative diseases. Rituximab is known to achieve systemic B-cell
depletion and clinical remission of the systemic effects of cryoglobulins in
hepatitis C virus-associated cryoglobulinemia. Conversely, there are few reports
regarding the use of rituximab in hepatitis B virus-associated cryoglobulinemia.
We report here the case of a 65-year-old Japanese female who presented with
lymphoproliferative disease-related cryoglobulinemia with hepatitis B virus,
including membranoproliferative glomerulonephritis with renal failure. The
vasculitis was refractory to conventional and antiviral therapy, but rituximab
use led to control the disease. Our case highlights the benefit and efficacy of
rituximab in association with antiviral therapy in small vessel vasculitis
related to lymphoproliferative disease-related cryoglobulinemia with hepatitis B
virus.
PMID- 28509275
TI - A case of acute interstitial nephritis and granulomatous hepatitis induced by
ingesting quinine.
AB - Quinine is used for the treatment of malarial infection, though not in common
use. It is especially valuable for the parenteral treatment of severe illness
owing to drug-resistant strains of Plasmodium falciparum. Quinine is also known
to occasionally cause acute renal failure (ARF). Although quinine is listed in
some reviews as a cause of acute interstitial nephritis, most cases of quinine
associated acute renal failure have been attributed to the hemolytic-uremic
syndrome (HUS). Only two cases of acute renal failure due to acute interstitial
nephritis associated with quinine have been reported [1, 2]. To our knowledge,
there have been 6 reported cases of quinine-induced hepatic granuloma [3-8]. We
report a case of quinine-induced acute interstitial nephritis (AIN) along with
granulomatous hepatitis, both of which were confirmed on biopsy. A 50-year-old
Nigerian man was admitted to the hospital with complaints of fever and general
fatigue. He had been prescribed quinine as an antimalarial drug in a Nigerian
hospital. The patient was febrile and showed nonoliguric ARF and liver
dysfunction. In this case, liver injury showed gradual and spontaneous resolution
after discontinuing quinine, and ARF resolved after treatment with oral
prednisolone.
PMID- 28509276
TI - A case of anaphylactoid reaction to acetate in acetate-containing bicarbonate
dialysate.
AB - A 35-year-old man with end-stage kidney disease due to chronic glomerulonephritis
was admitted to our hospital to start maintenance hemodialysis (HD). One hour
after starting the first session of HD, he experienced general pruritus,
urticaria, and dyspnea. Signs and symptoms were resolved by discontinuing HD and
administrating an antihistamine drug; HD-associated anaphylactoid reactions were
therefore suspected. Over the next few HD sessions, we changed the dialysis
membrane, anticoagulant, HD circuit and needle, in that order, but general
pruritus and urticaria again appeared within 3 h after starting each session of
HD. Finally, when we changed the dialysate from acetate-containing bicarbonate
dialysate to acetate-free bicarbonate dialysate, urticaria was clearly less than
that seen in previous HD sessions, and subsided after discontinuation of HD.
Subsequently, 20 mg of oral prednisolone (PSL) was administered 1 h before
starting HD, and the patient did not experience general pruritus, urticaria, or
dyspnea after starting the session. When administered acetate-containing
bicarbonate dialysate after oral PSL pretreatment, the patient again experienced
general pruritus, urticaria and dyspnea. Few reports have been published on the
occurrence of anaphylactoid reactions during HD using acetate dialysate. We
report a rare case of anaphylactoid reactions with acetate in acetate-containing
bicarbonate dialysate that were reduced with the use of acetate-free bicarbonate
dialysate and oral PSL pretreatment.
PMID- 28509277
TI - Two brothers with collagenofibrotic glomerulopathy.
AB - Collagenofibrotic glomerulopathy is a rare glomerular disease characterized by
extensive accumulation of atypical type III collagen fibers within the mesangial
matrix and subendothelial space. Laboratory evaluation of this disease shows a
marked increase in serum procollagen III peptide (P III P) levels. Here, we
report the case of two brothers with collagenofibrotic glomerulopathy confirmed
by histology. Patient 1 presented with proteinuria and hypertension and patient 2
presented with nephrotic-range proteinuria. Immunohistochemistry revealed strong
staining for antibodies to type III collagen in the widened subendothelial spaces
in both patients. Electron microscopy revealed numerous collagenous fibers in the
mesangium and subendothelial space. P III P levels were elevated in both
patients. Most reported cases of collagenofibrotic glomerulopathy, including the
adult-onset type, have been sporadic. Within the limits of our literature search,
this is only the third report of adult siblings with collagenofibrotic
glomerulopathy confirmed by histology. This report indicates that it may be
beneficial to measure serum P III P levels in the siblings of patients diagnosed
with adult-onset collagenofibrotic glomerulopathy.
PMID- 28509278
TI - A case of post-pneumococcal acute glomerulonephritis with glomerular depositions
of nephritis-associated plasmin receptor.
AB - We report the case of a 12-year-old girl who was referred to our hospital with
anuria associated with pneumonia. On admission, the patient's blood test results
revealed severe renal failure, hypoproteinemia, and hypocomplementemia. Her
urinalysis results revealed hematuria, proteinuria, and a positive titer for
Streptococcus pneumoniae. S. pneumoniae was also detected in her sputum and blood
cultures. The patient was diagnosed with post-pneumococcal acute
glomerulonephritis (AGN) with acute renal failure. A renal biopsy demonstrated
the infiltration of neutrophils and mononuclear cells into capillary loops.
Immunofluorescence studies showed dominant-positive deposition of C3c along the
capillary loops and nephritis-associated plasmin receptor (NAPlr) depositions in
the mesangial area and capillary loops. Electron microscopy revealed dense
deposits in the glomerular basement membrane without a hump in the subepithelial
area. These findings were consistent with endocapillary proliferative
glomerulonephritis. AGN associated with pneumococcal infection is very rare. This
case suggests that NAPlr is the causative antigen not only of post-streptococcal
AGN, but also of post-pneumococcal AGN. To our knowledge, this is the first
report that shows a relationship between post-pneumococcal AGN and NAPlr
depositions in the glomeruli.
PMID- 28509279
TI - A case of "hidden" diabetic nephropathy diagnosed by a combination of renal
biopsy findings and continuous glucose monitoring system.
AB - Although diabetic nephropathy is a microvascular complication of diabetes
mellitus, some reports suggest that renal biopsy often shows this pathological
change without a diagnosis of diabetes mellitus. Here, we report a case of a 65
year-old man who presented with proteinuria, hypoalbuminemia and hypertension
without a diagnosis of diabetes mellitus. He drank alcohol regularly and was a
heavy smoker. Renal biopsy revealed a diffuse increase in the mesangial area,
mesangial nodules or well-developed hyalinosis, interstitial fibrosis, and
arteriosclerosis consistent with the changes of diabetic nephropathy. Although we
had initially diagnosed him with idiopathic nodular glomerulosclerosis, use of a
continuous glucose monitoring system (CGMS) revealed that the changes in his
daily blood glucose concentrations met with the diagnostic criteria of diabetes
mellitus. Accordingly, we diagnosed him with diabetic nephropathy and initiated
treatment for diabetes mellitus. This case suggests that some cases of diabetic
nephropathy may be hidden among patients with impaired glucose tolerance, who are
not diagnosed with diabetes mellitus. Use of a CGMS may be helpful in diagnosing
this type of "hidden" diabetes mellitus. In addition to diet therapy, smoking
control, treatment for hypertension, and strict control of hyperglycemia may be
important for these patients.
PMID- 28509280
TI - A case of acute kidney injury and disseminated intravascular coagulation
associated with influenza B viral infection.
AB - There are few reports of acute kidney injury (AKI) associated with influenza
viral infection. We treated a case of AKI that developed after an influenza B
viral infection. A 35-year-old man visited a local physician for a fever and was
diagnosed with influenza B. He was prescribed laninamivir, then returned to the
physician 5 days later with dyspnea and was referred to Hospital A. Upon
admission, respiratory arrest developed, for which he received tracheal
intubation and mechanical ventilation. AKI was noted after admission and the
patient was transferred to our hospital the next day. AKI and disseminated
intravascular coagulation (DIC) were present at the time of transfer, thus a
transfusion and continuous hemodiafiltration (CHDF) were performed, and
administrations of thrombomodulin alpha and antithrombin III were initiated.
Although the patient had DIC, AKI, and disturbance of consciousness, and was in a
clinical state resembling influenza-associated encephalopathy, there was no clear
abnormality shown in CT scans of the head. Urine output, renal function, and
respiratory condition gradually improved, thus CHDF was stopped and extubation
performed. The patient had no complications and was discharged on hospital day
22. Some reports have been presented regarding cases of AKI due to rhabdomyolysis
associated with influenza viral infection, whereas our patient developed AKI as a
complication of an influenza B viral infection without rhabdomyolysis or
hemolytic uremic syndrome. Influenza B may cause AKI and DIC, and affected
patients can be in a serious condition requiring immediate attention.
PMID- 28509281
TI - Henoch-Schonlein purpura complicated with severe gastrointestinal bleeding.
AB - Bleeding from the gastrointestinal tract is one of the common determinants of
morbidity and mortality in the ordinary clinical setting. The gastrointestinal
involvement of Henoch-Schonlein purpura (HSP) has often been described as self
limiting, with no long-term morbidity. In this report, we describe our experience
with a male HSP patient who presented with abdominal pain, loss of appetite and
deteriorated renal function associated with nephrotic syndrome. Despite the use
of aggressive immunomodulatory treatments, including corticosteroids and
plasmapheresis, he developed lethal gastrointestinal hemorrhage. We believe that
the accumulation of more experience with additional cases similar to ours is
mandatory for the establishment of optimal management for HSP patients with
severe gastrointestinal manifestations.
PMID- 28509282
TI - Successful management of bilateral emphysematous pyelonephritis with abscess
formation in a chronic hemodialysis patient: a case report.
AB - Bilateral emphysematous pyelonephritis (EPN) has seldom been reported in patients
on maintenance hemodialysis (HD). Percutaneous catheter drainage (PCD) or
nephrectomy is often required in the treatment of bilateral EPN because of its
poor response to antimicrobial agents and high mortality rate. We report a
patient with bilateral EPN on maintenance HD. An octogenarian man with diabetes
mellitus who had previously undergone regular HD for 22 months was admitted to
our hospital because of severe inflammation resulting from bilateral EPN. His
lesions of EPN had resulted in abscess formation in both kidneys and right and
left side retroperitoneal space. As patient refused interventional therapy
including nephrectomy or PCD, he was treated conservatively. After treatment with
several antimicrobial agents for 50 days, he completely recovered from bilateral
EPN. To our knowledge, this is the first case report of successful conservative
management (antimicrobial therapy alone) of bilateral EPN that developed in a
chronic diabetic HD patient.
PMID- 28509283
TI - In Vivo Molecular MRI of ICAM-1 Expression on Endothelium and Leukocytes from
Subacute to Chronic Stages After Experimental Stroke.
AB - Molecular MRI allows in vivo detection of vascular cell adhesion molecules
expressed on inflamed endothelium, which enables detection of specific targets
for anti-neuroinflammatory treatment. We explored to what extent MR contrast
agent targeted to intercellular adhesion molecule-1 (ICAM-1) could detect
endothelial- and leukocyte-associated ICAM-1 expression at different stages after
experimental stroke. Furthermore, we assessed potential interfering effects of
ICAM-1-targeted contrast agent on post-stroke lesion growth. Micron-sized
particles of iron oxide (MPIO) functionalized with control IgG (IgG-MPIO) or anti
ICAM-1 antibody (alphaICAM-1-MPIO) were administrated at 1, 2, 3, 7, and 21 days
after unilateral transient middle cerebral artery occlusion in mice, followed by
in vivo MRI and postmortem immunohistochemistry. alphaICAM-1-MPIO induced
significant contrast effects in the lesion core on post-stroke days 1, 2, and 3,
and in the lesion borderzone and contralesional tissue on post-stroke day 2.
alphaICAM-1-MPIO were confined to ICAM-1-positive vessels and occasionally co
localized with leukocytes. On post-stroke day 21, abundant leukocyte-associated
alphaICAM-1-MPIO was immunohistochemically detected in the lesion core. However,
MRI-based detection of alphaICAM-1-MPIO-labeled leukocytes was confounded by pre
contrast MRI hypointensities, presumably caused by phagocytosed blood remains.
IgG-MPIO did not induce significant MRI contrast effects at 1 h after injection.
Lesion development was not affected by injection of alphaICAM-1-MPIO or IgG-MPIO.
alphaICAM-1-MPIO are suitable for in vivo MRI of ICAM-1 expression on vascular
endothelium and leukocytes at different stages after stroke. Development of
clinically applicable MPIO may offer unique opportunities for MRI-based diagnosis
of neuroinflammation and identification of anti-inflammatory targets in acute
stroke patients.
PMID- 28509284
TI - AP-VAS 2012 case report: a case of myeloperoxidase antineutrophil cytoplasmic
antibody-positive microscopic polyangiitis with rapidly progressive
glomerulonephritis and hearing loss.
AB - A 74-year-old Japanese woman was admitted to our hospital because of fever,
fatigue, and hearing loss associated with vertigo. She had a 1-year history of
hearing impairment that got worse gradually and had been treated as otitis media
with effusion, but without remarkable improvement. After admission, she developed
renal dysfunction associated with hematuria and proteinuria. Laboratory tests
showed leukocytosis and elevated C-reactive protein. Myeloperoxidase
antineutrophil cytoplasmic antibody (MPO-ANCA) was elevated, but proteinase-3
antineutrophil cytoplasmic antibody (PR3-ANCA) was negative. Renal biopsy
revealed pauci-immune focal necrotizing glomerulonephritis with crescents. She
was diagnosed as having MPO-ANCA-associated polyangiitis. After treatment with
500 mg methylprednisolone applied intravenously for 3 days, followed by 40 mg
prednisolone administered orally, renal function recovered completely. Her
hearing also improved. Although otolaryngological symptoms are common in PR3-ANCA
associated vasculitis, hearing loss is a rare manifestation of MPO-ANCA
associated vasculitis (MPO-AAV). Our case suggests that AAV should be considered
in the differential diagnosis of hearing loss.
PMID- 28509285
TI - AP-VAS 2012 case report: a case of lupus nephritis with predominant synchronous
cellular crescent formation and myeloperoxidase-antineutrophil cytoplasmic
antibody seropositivity.
AB - Several cases with an overlap of antineutrophil cytoplasmic antibody (ANCA)
associated glomerulonephritis (GN) and lupus nephritis (LN) features have been
reported in recent years. However, the clinical and the pathologic features of
this condition, including mode of development, histology, and response to
treatment, are not fully understood. We report a 77-year-old woman who was
diagnosed with Sjogren syndrome 15 years previously. The patient presented with
acute worsening of renal function and was diagnosed with new-onset systemic lupus
erythematosus. A renal biopsy specimen revealed proliferative LN with synchronous
cellular crescents. She was also seropositive for myeloperoxidase-ANCA. Together
with the positive staining for immunoglobulins and complement factors on
immunofluorescence microscopy and scant subendothelial deposits by electron
microscopy, we reached a diagnosis of ANCA-associated crescentic GN overlapping
with LN. Although immunosuppressive treatment with methylprednisolone pulse
therapy and intravenous cyclophosphamide followed by oral predonisolone was
initiated, along with intermittent hemodialysis, these treatments did not induce
remission of her GN. Therefore, she continued regular intermittent hemodialysis.
However, she died because of candida pneumonia 4 months after admission.
Generally, the glomeruli of patients with ANCA-associated GN exhibit different
stages of crescents, namely cellular, fibrocellular, or fibrous. The
histologically synchronous crescents in this case indicate that ANCA-associated
GN overlapping with LN can progress more rapidly than that without LN. This
overlapping type of GN may be resistant to conventional immunosuppressive
therapies.
PMID- 28509286
TI - Mizoribine as a safe and effective combined maintenance therapy with prednisolone
for anti-neutrophil cytoplasmic antibody-associated vasculitis in a hemodialysis
patient.
AB - A 77-year-old man developed severe renal insufficiency due to proteinase 3 anti
neutrophil cytoplasmic antibody (PR3-ANCA)-associated vasculitis, and was started
on hemodialysis (HD). Because his renal insufficiency appeared to be
irreversible, he was maintained on oral prednisolone (PSL) at 5 mg/day. However,
a disease flare-up with alveolar hemorrhage occurred. Serology revealed elevated
levels of PR3-ANCA and C-reactive protein (CRP). The patient was given pulse
therapy with a quarter dose of methylprednisolone (m-PSL) (250 mg, 3 days),
followed by oral PSL at 15 mg/day. As a supplemental treatment, he was given 25
mg of mizoribine (MZR) immediately after each HD session. Subsequently, the
levels of PR3-ANCA and CRP decreased, and the alveolar hemorrhage resolved. The
dose of MZR to be given was determined by measuring the patient's serum
concentrations of MZR at various time points after the HD session. The
maintenance dose of MZR was finally set at 50 mg. At present, the oral PSL dosage
has been tapered to 10 mg/day, and the patient has achieved a state of remission
without any side effects.
PMID- 28509287
TI - Unusually indolent MPO-ANCA: associated vasculitis-report of two cases.
AB - Vasculitis associated with antineutrophil cytoplasmic antibodies specific to
myeloperoxidase generally presents as a life- and organ-threatening disease that
evolves over several months. It is a syndrome in which prompt diagnosis and
therapy are important both in terms of short-term survival and long-term organ
damage. Two cases with quite a different course, sustained and indolent with
limited progression over many years, are described in this report. They are
compared to cases in the literature. Indolent cases of granulomatous polyangiitis
associated with antineutrophil cytoplasmic antibodies against proteinase-3 are
well recognised, but these two cases of microscopic polyangiitis are almost
unique.
PMID- 28509288
TI - Severe hyponatremia caused by secondary adrenal insufficiency in a patient with
giant pituitary prolactinoma.
AB - A 55-year-old-man was admitted to Saiseikai Central Hospital, Tokyo, Japan,
complaining of nausea and appetite loss, and was found to have severe
hyponatremia. Despite severe hyponatremia and plasma hypo-osmolarity, urinary
sodium excretion was not reduced. A brain magnetic resonance imaging (MRI) scan
revealed a giant pituitary prolactinoma, and endocrinological tests showed a
markedly increased prolactin level. Despite the observation that the basal plasma
ACTH level was normal, serum cortisol and urinary cortisol excretion levels were
low. Rapid ACTH loading sufficiently stimulated an increase in serum cortisol
levels, suggesting secondary adrenal insufficiency. Notably, loading of CRH
induced a good ACTH response; however, the serum cortisol response remained low.
In contrast, the continuous daily administration of exogenous ACTH dramatically
increased serum cortisol levels. These discrepant responses may have been caused
by the low biological activity of innate ACTH. Following partial resection of the
prolactinoma, postoperative adjuvant therapy with cabergoline effectively reduced
prolactin levels, but did not improve the hyponatremia. In contrast,
hydrocortisone replacement therapy recovered the serum sodium level to the normal
range. The present case is the first report describing a link between severe
hyponatremia and biologically inactive circulating ACTH as a likely result of
giant prolactinoma.
PMID- 28509289
TI - AP-VAS 2012 case report: a case of systemic MPO-ANCA-associated vasculitis that
demonstrated brain infarction and immunohistochemically MPO-positive capillaries.
AB - We present a case of an aged male with myeloperoxidase anti-neutrophil
cytoplasmic autoantibody (MPO-ANCA)-associated vasculitis with onset of brain
infarction that demonstrated immunohistochemically MPO-positive capillaries at
autopsy. The patient initially presented with gait difficulty and right-sided
weakness. Since an imaging study revealed brain infarction, he was admitted to
our hospital and medicated by antiplatelet agents. Continuous fever and elevated
serum C-reactive protein (CRP), hematuria of glomerular origin, renal
dysfunction, and high serum titer of MPO-ANCA were detected. Systemic toxicoderma
appeared, and skin biopsy revealed small-vessel vasculitis; thus, he was
diagnosed with MPO-ANCA-associated vasculitis. Steroid therapy
(methylprednisolone 30 mg/day) was started, and general status improved. However,
he died of shock 6 days after the start of the therapy. Autopsy revealed massive
retroperitoneal hemorrhage with necrotizing small-vessel vasculitis in systemic
organs including retroperitoneum, skin, brain, testes, and kidneys.
Immunohistochemically, infiltration of MPO-positive white blood cells into the
capillaries was occasionally observed, along with the features of MPO-positive
capillaries. Cerebrovascular involvement of MPO-ANCA-associated vasculitis is
rare compared with renal and pulmonary manifestations, having been reported to
occur in up to 4 % of patients. Furthermore, as we have recently reported, MPO
immunopositive capillaries may appear only during the hyperacute stage of the
disease. Therefore, the present case represents the unique combination of these
two rare manifestations.
PMID- 28509290
TI - A case of infantile systemic lupus erythematosus with severe lupus nephritis and
EBV infection.
AB - Infantile systemic lupus erythematosus (iSLE) is extremely rare. Patients with
iSLE usually become severely unwell and have poor prognosis. Epstein-Barr virus
(EBV) infection has been implicated in the development of SLE in both adults and
children. Recently, we experienced a case of iSLE with severe lupus nephritis
(LN) and EBV infection. A 14-month-old Japanese boy was diagnosed with iSLE
according to the American Rheumatism Association criteria. Renal biopsy showed LN
classified as International Society of Nephrology/Renal Pathology Society class
IV-G (A), and liver biopsy showed lupus hepatitis. Steroid pulse treatment
resulted in improvement of the levels of serological markers of SLE such as
double-stranded DNA and complement, but his proteinuria worsened and he developed
acute nephritic-nephrotic syndrome. Monthly intravenous cyclophosphamide (IVCY)
therapy dramatically reduced his proteinuria and led to complete remission
(urinary protein/creatinine ratio <0.1 mg/mg), with gradual improvement in levels
of serological markers. EBV antibody titers and EBV polymerase chain reaction
(PCR) of peripheral blood lymphocytes suggested that the onset of iSLE might have
been associated with EBV infection. At his 2-year follow-up visit, he was healthy
and remained in complete remission. We conclude that IVCY treatment might be well
tolerated and effective in cases of iSLE. EBV infection might play an important
role in the pathogenesis of iSLE.
PMID- 28509291
TI - Nephrotic-range proteinuria in an infant with thin basement membrane nephropathy.
AB - Thin basement membrane nephropathy (TBMN) with heterozygous COL4A3/COL4A4
mutations is considered to be a cause of benign familial hematuria. The disease
has been believed to have excellent prognosis and TBMN in early childhood is
rarely associated with nephrotic-range proteinuria. Furthermore, the presence of
proteinuria in patients with TBMN is associated with autosomal-dominant Alport
syndrome, which has poorer prognosis in later life. We present an infant case of
nephrotic-range proteinuria associated with TBMN caused by heterozygous COL4A4
mutation. A previously healthy 3-year-old boy developed microhematuria and
nephrotic-range proteinuria. Renal pathology simply revealed thinning of the
glomerular basement membrane (GBM) and mutational analysis revealed a novel
heterozygous mutation in COL4A4. He was treated with lisinopril for 1.5 years,
which resolved his proteinuria and hematuria. At the most recent follow-up at 6.5
years of age, urinalysis and kidney function were completely normal, without
requiring medication. However, transient but repeated moderate to nephrotic-range
proteinuria and microscopic hematuria occurred in association with other
illnesses. This case highlights the spectrum of phenotypes that may be apparent
in an infant with TBMN. Thinning of the GBM can cause transient nephrotic-range
proteinuria, particularly in the early stages of TBMN.
PMID- 28509292
TI - Granulomatosis with polyangiitis associated with IgA nephropathy.
AB - Granulomatosis with polyangiitis (GPA), previously referred to as Wegener's
granulomatosis, is a rare necrotizing granulomatous vasculitis, especially in
children. GPA affects small- to medium-sized vessels, leading to involvement of
multiple organs, including the upper and lower respiratory tracts and kidneys.
Glomerular lesions associated with GPA typically present as crescentic
glomerulonephritis with necrotizing lesions, with little or no staining for
immunoglobulins and complement proteins. We report a unique pediatric case of GPA
associated with IgA nephropathy, a representative immune-mediated glomerular
disease. The initial renal biopsy specimen revealed fibrous sclerosis and mild
mesangial proliferation without deposition of IgA. However, after clinical
remission of GPA by treatment, the serum IgA level continued to be significantly
higher than normal, and her paranasal sinusitis was poorly controlled. An acute
upper respiratory infection resulted in worsened urinary findings without any
systemic signs of GPA. The second renal biopsy specimen revealed deposition of
IgA and C3 in the mesangium. The patient was treated with oral prednisolone
alone, which led to complete remission of proteinuria within 1 month. IgA
nephropathy is possibly associated with GPA during remission stage, and serum IgA
level may be a valuable indicator to predict its association.
PMID- 28509293
TI - Proliferative glomerulonephritis with monoclonal IgG2kappa deposit successfully
treated with steroids: a case report and review of the literature.
AB - A novel form of glomerular injury with monoclonal immunoglobulin (Ig) IgG
deposition, termed "proliferative glomerulonephritis (GN) with monoclonal IgG
deposits" (PGNMID), is a recently described entity. PGNMID presents with various
histological patterns, such as membranoproliferative GN, endocapillary
proliferative GN and membranous nephropathy (MN). The deposits are composed of
monoclonal immunoglobulin, most commonly IgG3 and occasionally IgG2. At present,
the clinical significance of each IgG subclass and the morphological patterns of
glomerular injury have not been fully investigated due to the limited number of
PGNMID cases reported. The patient was a 27-year-old woman presenting with a mild
degree of proteinuria and no other physical or serological abnormalities.
Monoclonal Ig could not be identified in her serum or urine. Renal biopsy found
features of MN with deposition of monoclonal IgG2kappa. Electron microscopy
examination revealed non-organised electron-dense deposits predominantly in
subepithelial locations. Based on a diagnosis of PGNMID, she was treated with
prednisolone and proteinuria significantly decreased in less than 4 weeks.
Although the clinical outcomes of PGNMID remain to be defined, MN features may
possibly be a sign of favourable prognosis-a hypothesis supported by recent
reports. The absence of advanced chronic damage in the kidney, such as
glomerulosclerosis or tubulointerstitial fibrosis, may also have contributed to
the favourable outcome in the present case. Further studies on additional PGNMID
cases that allow the correlation of morphological features and IgG subclasses
with clinical outcomes are needed in order to confirm our findings and further
solidify the clinical aspects of this new disease entity.
PMID- 28509294
TI - Proliferative glomerulonephritis with monoclonal IgM-kappa deposits in chronic
lymphocytic leukemia/small lymphocytic leukemia: case report and review of the
literature.
AB - A 48-year-old man with chronic lymphocytic leukemia presented with nephrotic
syndrome, hematuria, and mild deterioration of renal function. Further analysis
using serum immunofixation electrophoresis detected monoclonal immunoglobulin
(Ig) M-kappa and IgG-kappa M-protein. Testing for cryoglobulin in serum was
negative. Light microscopy of a renal biopsy specimen showed
membranoproliferative glomerulonephritis features with marked mononuclear cell
infiltration in the interstitium. On immunofluorescence study, the deposition of
IgM heavy chain was predominantly observed with the same distribution of kappa
light chain, whereas no lambda light chain was found. Electron microscopy
revealed fine granular deposits in the mesangial, subendothelial, and
subepithelial areas, mimicking those observed in the immune complex-mediated
glomerulonephritis. These pathological findings were consistent with recently
described cases of proliferative glomerulonephritis with monoclonal IgG deposits.
Thus, monoclonal IgM deposition can also cause proliferative glomerulonephritis.
PMID- 28509295
TI - Antineutrophil cytoplasmic antibody-associated crescentic glomerulonephritis with
membranous nephropathy treated using thiamazole.
AB - A 21-year-old woman with nephrotic syndrome was referred to our hospital. She had
congenital diaphragmatic hernia, hypoxic ischemic encephalopathy, and mental
retardation, and had been treated for hyperthyroidism with thiamazole in another
hospital. Serum creatinine was 37.8 MUmol/L and antineutrophil cytoplasmic
antibody against myeloperoxidase (MPO-ANCA) was 39 EU. Urinalyses were 3+ for
proteins and 3+ for occult blood. A renal biopsy was performed. An examination
using light microscopy (LM) revealed necrotizing glomerulonephritis with crescent
formation. Immunofluorescence microscopy showed granular staining with
immunoglobulin G and complement component 3 along the capillary walls. Electron
microscopy (EM) disclosed subepithelial dense deposits. A renal biopsy suggested
necrotizing glomerulonephritis with membranous nephropathy (MN) in stages I or
II. Since many cases of drug-induced ANCA-associated glomerulonephritis (AAG)
have been reported, we stopped thiamazole and treated with corticosteroid. The
MPO-ANCA titer became negative 49 days after the initiation of treatment. Two
years after the first treatment, the MPO-ANCA titer became elevated again and was
82 EU. The patient was administered cyclophosphamide and prednisone. However, the
MPO-ANCA titer did not decrease. A renal biopsy was performed again 3 years after
the first renal biopsy. LM revealed no crescentic formation but demonstrated
spike formations along the glomerular basement membrane. EM also disclosed
subepithelial dense deposits, but less than the first biopsy. The renal biopsy
suggested MN in stages II or III. AAG was regarded as inactive after
corticosteroid treatment. Therefore, ciclosporin administration was started. In
conclusion, we experienced a rare case of AAG complicated with MN. The
histopathologic results showed that immunosuppressive therapy seemed to be
effective in treating crescentic glomerulonephritis; furthermore, it reduced
proteinuria but could not reduce the MPO-ANCA titer.
PMID- 28509296
TI - Renal biopsy cases in myeloproliferative neoplasms (MPN).
AB - We performed renal biopsy in three cases complicated by myeloproliferative
neoplasms (MPN). Although several cases of glomerulonephritis associated with MPN
have been reported, the etiologies of the renal disorders were not established
(Plomley et al., Aust NZ J Med, 13:125-129, 1983; Sharma et al., Nephron, 69:361,
1995; Kanauchi et al., Intern Med, 33:36-40, 1994; Kasuno et al., Nephrol Dial
Transplant, 12:212-215, 1997; Au et al., Am J Kid Dis, 34:889-893, 1999; Kosch et
al., Nephrol Dial Transplant, 15:1710-1711, 2000; Oymak et al., Nephron, 86:346
347, 2000; Chun et al., Am J Nephrol, 20:344-346, 2000; Chung et al., Am J
Nephrol, 22:397-401, 2002; Asaba et al., Clin Exp Nephrol, 7:296-300, 2003;
Haraguchi et al., Clin Exp Nephrol, 10:74-77, 2006; Saigusa et al., J Nephrol,
19:656-658, 2006; Okuyama et al., Clin Nephrol, 6:412-415, 2007; Nishi et al.,
Clin Nephrol, 5:393-398, 2010; Ulusoy et al., Intern Med, 49:2477, 2010). A
review of previous reports of renal biopsy cases with MPN in the English
literature suggested that circulation control is important for the treatment of
renal disorders that mimic glomerulonephritis in MPN.
PMID- 28509297
TI - AP-VAS 2012 case report: a case of ANCA-negative pauci-immune crescentic
glomerulonephritis associated with IL-6-producing adenosquamous cell carcinoma of
the lung.
AB - A 76-year-old man with lung cancer and multiple metastases was admitted for
purpura and rapidly progressive glomerulonephritis. Adenosquamous cell carcinoma
of the lung had been diagnosed 6 months earlier. Two anti-cancer drug regimens
had no effect. At admission, his survival with his malignancy was estimated to be
several months. Renal biopsy revealed pauci-immune necrotizing crescentic
glomerulonephritis (CrGN). Negative results were obtained for myeloperoxidase
anti-neutrophil cytoplasmic antibody (ANCA) and proteinase-3-ANCA by enzyme
linked immunosorbent assay, and for peripheral-ANCA and cytoplasmic-ANCA by
indirect immunofluorescence. He was diagnosed with ANCA-negative pauci-immune
CrGN. Although steroids were initiated, the patient died of renal failure and
intestinal bleeding 2 weeks later. It was later found that cancer cells were
positive for interleukin (IL)-6 and that serum IL-6 levels were significantly
elevated, concomitantly with increased IL-8, granulocyte-colony stimulating
factor and transforming growth factor-beta levels. Some kinds of lung cancer are
known to produce IL-6 that activate neutrophils and are related to ANCA
associated CrGN. It appears that IL-6 can activate neutrophils in the
pathogenesis of ANCA-negative pauci-immune CrGN with lung cancer. Therapy that
blocks IL-6 may prove to be effective in vasculitis and cancer-related symptoms
in such cases.
PMID- 28509298
TI - A rare case: childhood-onset C3 glomerulonephritis due to homozygous factor H
deficiency.
AB - C3 glomerulopathy is a recently described pathological entity including dense
deposit disease and C3 glomerulonephritis (C3GN). In some cases, C3
glomerulopathy is associated with defects or even complete deficiency of factor
H. However, complete factor H deficiency among patients with C3GN is rare, and
paediatric cases have not yet been described. Here, we report a child with
homozygous factor H deficiency who presented with haematuria and minor
proteinuria, together with undetectable plasma C3 levels, at the age of 10 years.
Kidney biopsy demonstrated C3GN. Detailed complement analysis revealed complete
factor H deficiency due to a homozygous CFH mutation. Furthermore, there was a
complete deletion of CFHR-1/-3. During follow-up, the patient has had recurrent
episodes of macro-haematuria and minor proteinuria, but during 4 years of follow
up, no deterioration of renal function has been observed. Mutations of factor H
in C3GN have been described; however, complete CFH deficiency is rare in these
patients. Furthermore, clinical presentation usually occurs in adulthood.
Therefore, this case presents a rare manifestation of the disease and might
contribute to the early detection of similar cases also in childhood.
PMID- 28509299
TI - Development of minimal-change glomerular disease and Hashimoto's thyroiditis
during the treatment of sarcoidosis.
AB - Minimal-change glomerular disease, sarcoidosis and autoimmune thyroid disease
rarely occur in the same patient. We herein report a patient in which minimal
change glomerular disease and Hashimoto's thyroiditis developed during the
treatment of sarcoidosis with steroids. A 66-year-old female was admitted to our
hospital with symptoms of nephrotic syndrome. Nine months before admission, she
was diagnosed as having ocular and pulmonary sarcoidosis, for which prednisolone
at an initial dose of 40 mg/day was started. When the dose of prednisolone was
tapered to 20 mg/day, she noticed swelling of the lower extremities. Examination
confirmed the simultaneous occurrence of minimal-change glomerular disease and
Hashimoto's thyroiditis, which were diagnosed based on kidney histology,
ultrasonography of the thyroid gland and positive antithyroglobulin antibodies.
We used intravenous methylprednisolone pulse therapy followed by 40 mg/day oral
prednisolone. The patient achieved complete remission of nephrotic syndrome and
steroids were tapered without relapse.
PMID- 28509300
TI - Pulmonary and gastric metastatic calcification due to milk-alkali syndrome: a
case report.
AB - The incidence of metastatic calcification is influenced by high serum calcium and
phosphate concentrations and local physicochemical conditions, such as pH. A high
pH accelerates tissue calcification. Patients with milk-alkali syndrome typically
present with renal failure, hypercalcemia, and metabolic alkalosis, which are
caused by the ingestion of calcium and absorbable alkali. Among patients with
impairment of renal function, milk-alkali syndrome is a major cause of
hypercalcemia. Long-term use of furosemide will lead to hypokalemia, metabolic
alkalosis, and eventually renal failure (i.e., pseudo-Bartter syndrome). Even if
the level of calcium ingestion is relatively low, the renal failure caused by
long-term furosemide use can readily lead to milk-alkali syndrome. We describe a
case of a 45-year-old woman who was admitted with cough and dyspnea and presented
with pulmonary and gastric metastatic calcification. She had been taking
alfacalcidol and oral alkaline medications such as sodium bicarbonate and calcium
carbonate as well as oral furosemide for a long time. The patient was found to
have hypercalcemia, chronic renal failure, and metabolic alkalosis, so milk
alkali syndrome was diagnosed. Saline was administered and oral medications were
discontinued. Serum creatinine levels subsequently decreased, but pulmonary
metastatic calcification was not diminished. In this case, the milk-alkali
syndrome that caused the severe metastatic calcification was exacerbated by
multiple factors, including oral alkaline medications such as sodium bicarbonate
and calcium carbonate. In addition, metabolic alkalosis and renal failure were
affected by long-term furosemide use (i.e., pseudo-Bartter syndrome).
PMID- 28509301
TI - AP-VAS 2012 case report: anti-glomerular basement membrane disease with high
titer of myeloperoxidase anti-neutrophil cytoplasmic antibody-an autopsy case
report.
AB - It has been reported that patients who are positive for both myeloperoxidase anti
neutrophil cytoplasmic antibody (MPO-ANCA) and anti-glomerular basement membrane
(GBM) antibody have a poor prognosis. We present an autopsy case of anti-GBM
disease with a high titer of MPO-ANCA. The patient was a 77-year-old woman with a
medical history of idiopathic interstitial pneumonia. After being treated for
bacterial pneumonia, she was referred to our hospital for evaluation of non
nephrotic range proteinuria, hematuria, and a course of rapidly progressive
glomerulonephritis. Results of urinalysis were 2+ for protein and 3+ for blood,
with many dysmorphic red blood cells observed in the urinary sediment. A sample
of a 24-h urine collection contained 0.3 g protein. The serum creatinine
concentration was 5.0 mg/dl on admission. The patient tested positive for MPO
ANCA at a titer of >640 EU and for anti-GBM antibody at a titer of 14 EU. Renal
biopsy revealed glomerulonephritis with crescent formation, and
immunofluorescence studies showed that the glomeruli had a generalized linear
fluorescence and anti-immunoglobulin G (IgG) and C3 along the peripheral
glomerular capillaries. She was diagnosed with anti-GBM disease. Treatment was
started with intravenous prednisolone and oral cyclophosphamide, followed by
plasma exchange. Despite improved renal function, she died of pulmonary
hemorrhage. Autopsy revealed deposits of IgG and C3 in the basement membranes of
lung alveoli.
PMID- 28509303
TI - A novel mutation in the uromodulin gene in a Japanese family with a mild
phenotype of familial juvenile hyperuricemic nephropathy.
AB - Familial juvenile hyperuricemic nephropathy (FJHN) is an autosomal-dominant
disorder that is characterized by hyperuricemia and chronic renal failure and
results in end-stage renal failure. FJHN is caused by mutations in the UMOD gene,
which encodes uromodulin. Uromodulin contains three epidermal growth factor (EGF)
like domains, a domain of eight cysteine residues (D8C), and a zona pellucid-like
domain. Over 90 % of UMOD mutations are missense mutations, and over 80 % exist
in exon 4, which encodes both D8C and the EGF-like domains. A 56-year-old woman
was diagnosed with hyperuricemia with a serum uric acid level of 7.5 mg/dL, and
stage III chronic kidney disease (CKD) with a serum creatinine level of 1.12
mg/dL and an estimated glomerular filtration rate of 39.9 mL/(min 1.73 m2). The
patient had a family history of hyperuricemia and stage IV CKD; both the patient
and her affected family members had a novel mutation in the UMOD gene: c.C518G
(p.P173R), located between the EGF-like domains and D8C. This mutation, along
with previously reported nearby mutations, causes a clinically mild phenotype of
FJHN. It is important that physicians consider the diagnosis of FJHN in patients
with a family history of hyperuricemia associated with renal dysfunction, even if
the patient has only mild renal impairment.
PMID- 28509302
TI - A case of disseminated tuberculosis after the initiation of hemodialysis.
AB - A 67-year-old man with diabetes mellitus, chronic kidney disease, chronic heart
failure, and amputation of the left lower limb was admitted to our hospital with
decreasing renal function. On admission, he was started on hemodialysis. He
simultaneously developed a urinary tract infection, infected necrotic wound of
the right lower limb, and pneumonia, and was treated with broad-spectrum
antibiotics. Although his general condition improved, fever and anorexia
persisted and jaundice worsened. He died 138 days after admission. Autopsy
revealed granulomas in the lungs, liver, and spleen. Cultures revealed
Mycobacterium tuberculosis, leading to the diagnosis of disseminated
tuberculosis.
PMID- 28509305
TI - AP-VAS 2012 case report: two patients with rheumatoid arthritis suspected of
relapsed microscopic polyangiitis after initiation of dialysis.
AB - We report two patients with rheumatoid arthritis (RA) who were suspected of
microscopic polyangiitis during maintenance dialysis. Case 1 was a 52-year-old
woman with RA diagnosed at the age of 38 years and treated successfully with gold
compounds. At the age of 43 years, she presented with progressive renal
dysfunction and abnormal urine sediments, and a renal biopsy revealed crescentic
nephritis with advanced glomerular sclerosis. Myeloperoxidase antineutrophil
cytoplasmic antibody (MPO-ANCA) was not measured on that occasion. She reached
end-stage renal failure within 4 months and started peritoneal dialysis. Eight
years later, soon after she was switched to hemodialysis, she developed fever of
unknown origin. MPO-ANCA was elevated to 37 EU, although there were no other
signs or symptoms suggestive of vasculitis. After taking prednisolone orally (10
mg/day), her fever withdrew, and MPO-ANCA became undetectable. Case 2 was a 71
year-old woman with RA diagnosed at the age of 60 years and treated with gold
compounds. She developed renal failure of unknown cause (no biopsy was
performed), and started hemodialysis at the age of 69 years. One year later, she
presented with fever and subsequently developed cough with hemoptysis. MPO-ANCA
was elevated to 62 EU. Treatment with azathioprine 50 mg and prednisolone 35 mg
daily brought remarkable clinical improvement, and MPO-ANCA became undetectable.
These cases highlight the importance of measuring ANCA even in RA patients on
dialysis who present with fever of unknown origin or with underlying kidney
disease of uncertain etiology.
PMID- 28509304
TI - A case of anti-GBM glomerulonephritis superimposed on HBV-associated membranous
nephropathy.
AB - In September 2010, a 75-year-old hepatitis B virus (HBV)-positive man was
admitted to our hospital because of fever, persistent cough, general fatigue, and
leg edema. The patient was a hepatitis B surface antigen carrier with detectable
HBV DNA level. On admission, laboratory examination revealed severe inflammatory
signs, decreased serum albumin, and renal insufficiency with proteinuria. The
patient had rapidly progressive renal insufficiency without pulmonary involvement
over the few days after admission. Renal biopsy showed membranous nephropathy
(MN) with crescent formation. Further serological study revealed a high titer of
anti-glomerular basement membrane (GBM) antibody, suggestive of anti-GBM
glomerulonephritis superimposed on HBV-associated MN. For both preventing HBV
reactivation during immunosuppressive therapy and treating HBV-associated MN, the
administration of entecavir was immediately initiated, and then treatment with
plasma exchange (PE) and intravenous methylprednisolone administration was
performed. Both HBV DNA level and an anti-GBM titer became undetectable, and
clinical remission of MN was subsequently achieved. This was a rare case of an
elderly patient with anti-GBM glomerulonephritis superimposed on HBV-associated
MN, who was successfully treated with PE, corticosteroid, and entecavir
combination therapy.
PMID- 28509308
TI - List of referees.
PMID- 28509306
TI - AP-VAS 2012 case report: a case of ANCA-negative crescentic glomerulonephritis
complicating multiple opportunistic infections in the digestive tract.
AB - Crescentic glomerulonephritis (GN) is one of the common causes of rapidly
progressive glomerulonephritis (RPGN). Pauci-immune crescentic GN is usually
associated with anti-neutrophil cytoplasmic antibody (ANCA). However, patients
with pauci-immune crescentic GN who lack ANCAs have recently been reported.
Approximately 10-30 % of patients with pauci-immune crescentic GN lack ANCAs. The
clinical characteristics of patients with ANCA-negative pauci-immune crescentic
GN are not entirely the same as patients with ANCA-positive GN, and this suggests
that ANCA-negative and ANCA-positive pauci-immune crescentic GN might be
different disease entities. We report a patient with ANCA-negative crescentic GN
complicated with multiple opportunistic infections (Candida albicans, herpes
simplex virus, and Cytomegalovirus) in the digestive tract during the course of
immunosuppressive therapy. After antifungal and antiviral therapies including
itraconazole, valaciclovir, and ganciclovir, she recovered from multiple
opportunistic infections. The occurrence of comorbid opportunistic infections
during the course of immunosuppressive therapy may not be rare in the elderly.
However, a case of multiple opportunistic infections limited to the digestive
tract is very rare.
PMID- 28509307
TI - AP-VAS 2012 case report: MPO-ANCA-negative relapse of MPO-ANCA-associated
vasculitis.
AB - A 79-year-old female was admitted to our hospital with fever, proteinuria,
hematuria, high levels of C-reactive protein (CRP), and high titer of
myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA). Our diagnosis was
microscopic polyangiitis (MPA) and she was treated with steroid pulse therapy.
Clinical remission was induced; however, the disease relapsed with saddle nose
and necrotizing vasculitis of the nasal cavity mucosa 1 year later. Although
there was no elevation of the MPO-ANCA titer, we diagnosed the patient with
relapse of MPO-ANCA-positive granulomatosis with polyangiitis (GPA). Remission
was induced again with steroids and azathioprine. It has been reported that the
number of MPO-ANCA-positive patients in Asian countries is relatively higher than
in Western countries. We checked 29 GPA patients in our hospital and 9 patients
(31.0 %) were MPO-ANCA-positive. In addition, it is not rare that an ANCA
associated vasculitis (AAV) patient who has been in remission with negative ANCA
relapses without any elevation of ANCA titer. We checked the transition of ANCA
titer of 24 AAV patients in our hospital who relapsed and 6 patients (25 %)
relapsed without any elevation of ANCA titer. We should be careful for a relapse,
even if the ANCA titer remains negative. It is also possible that ANCA had been
changed so as not to be detected by the same enzyme-linked immunosorbent assay
(ELISA) kit. Thus, it is also important to change the detection system if
clinical symptoms are worsened while ANCA is still negative.
PMID- 28509309
TI - Epidemiological profile and antibiotic resistance of Pseudomonas aeruginosa
isolates in burn and Traumatology center in Tunisia over a three-year period.
AB - BACKGROUND: Pseudomonas aeruginosa is a known opportunistic pathogen frequently
causing serious infections in burned patients. AIM: To analyze the
epidemiological profile of Pseudomonas aeruginosa isolated in a Tunisian burn
unit. METHODS: During a 3-year period (from 01 July 2008 to 30 June 2011), 544
non repetitive strains of P. aeruginosa were isolated from burn patients.
Susceptibility to antibiotics was assessed according to CA-SFM guidelines.
Serotypes were identified by slide agglutination test using P.aeruginosa O
antisera (Biorad). Producing carbapenemase was analyzed for 202 imipenem
resistant isolates by EDTAtest. Susceptibility testing data were stored in a
laboratory data base using whonet 5.3 software. RESULTS: The most frequent sites
of isolation were cutaneous infections and blood cultures (83.4%). The
percentages of resistant isolates were as follows: ceftazidime: 34%; imipenem:
37.1%, ciprofloxacin: 27.1% and amikacin: 29.6%. The most prevalent serotypes
were: 011(51%), 06(17%), 03 (8%), 04(12%), 012(5%). Among the 202 imipenem
resistant strains, 58% expressed a metallocarbapenemase. All theses strains were
resistant to all tested antibiotics except colistin and belonged to the serotype
O11. CONCLUSION: The dissemination of carbapenemases strains must be contained by
implementation of timely identification, strict isolation methods and better
hygienic procedures.
PMID- 28509310
TI - Circulating tumor cells in different stages of colorectal cancer.
AB - INTRODUCTION: Liquid biopsies are noninvasive tests using blood or body fluids to
detect circulating tumor cells (CTCs) or the products of tumor cells, such as
fragments of nucleic acids or proteins that are shed into biological fluids from
primary tumor or its metastates. The analysis of published clinical studies
provides coherent evidence that the presence of CTCs detected in peripheral blood
is a strong prognostic factor in patients with colorectal carcinoma (CRC). The
aim of the study was to implement size-based separation protocol of CTCs in CRC
patients. MATERIAL AND METHODS: Patients diagnosed with different stages of CRC
(n = 98) were included in the study. All patients have been diagnosed for
colorectal adenocarcinoma by pathology examination, 45 patients with colon
carcinoma and 53 with rectosigmoid cancer. A size-based separation method
(MetaCell(r)) for viable CTC enrichment from peripheral blood was used to assess
the presence of CTCs by cytomorphological evaluation using vital fluorescence
microscopy. RESULTS: Cytomorphological analysis revealed that 81 (83%) tested
samples were CTC-positive and 17 (17%) were CTC-negative. We report a successful
isolation of CTCs with proliferation potential in patients with CRC. The CTCs
were cultured in vitro for further downstream applications. Some of the isolated
CTCs were able to grow in vitro for 6 months as a standard cell culture.
CONCLUSIONS: We established a reliable, inexpensive and relatively fast protocol
for CTCs enrichment in CRC patients by means of vital fluorescence staining which
enables their further analysis in vitro.
PMID- 28509311
TI - Ultrastructural characteristics of myenteric plexus in patients with colorectal
cancer.
AB - INTRODUCTION: It have been found previously that colorectal cancer (CRC) is
accompanied by atrophy of myenteric plexuses (MPs) localized close to the tumor.
The aim of the study was to compare ultrastructure of MPs localized in the
unchanged part of the colon wall distant to CRC tumor with the ultrastructure of
MPs in the vicinity of CRC tumor. MATERIAL AND METHODS: The present study was
conducted using post-operative material derived from 11 patients with CRC.
Samples of colon wall were taken from the margin of cancer invasion and from a
macroscopically unchanged segment of the large intestine, immediately fixed and
processed according to the standard protocol for transmission electron microscopy
studies. RESULTS: In the MPs localized in the control part of colon wall the
presence of numerous unmyelinated axons and cell bodies of neurons, interstitial
cells of Cajal and enteroglial cells were observed. As compared to control
samples, in the MPs located close to the tumor invasion, expansion of the
extracellular matrix and myelin-like structures accompanying some nerve fibers
were found. The appearance of mast and plasma cells was observed within MPs in
the vicinity of CRC tumor. Sporadically, apoptotic cells were present inside the
MPs. CONCLUSIONS: The presence of myelin-like structures and apoptotic cells
within MPs located close to tumor invasion suggests that atrophy of MPs may be
caused by factors released from CRC tumor.
PMID- 28509312
TI - Histological, immunohistochemical and ultrastructural study of secondary
compressed spinal cord injury in a rat model.
AB - INTRODUCTION: Spinal cord injury (SCI) is a life-disrupting condition in which
the first few days are the most critical. Secondary conditions remain the main
causes of death for people with SCI. The response of different cell types to SCI
and their role at different times in the progression of secondary degeneration
are not well understood. The aim of this study was to study the histopathological
changes of compressed spinal cord injury (CSCI) in a rat model. MATERIAL AND
METHODS: Forty adult male Sprague-Dawley rats were divided into four groups. In
group I, the rats were left without any surgical intervention (control). In group
II, the rats were subjected to laminectomy without spinal cord compression (sham
operated). In group III, the rats were sacrificed one day after CSCI. In group
IV, the rats were sacrificed seven days after CSCI. The light microscopy was
employed to study the morphology using H&E, osmic acid staining and
immunohistochemistry to detect glial fibrillary acidic protein (GFAP). The
electron microscopy was applied for ultrastructure study. RESULTS:
Histopathological examination of the posterior funiculus of the white matter
revealed minute hemorrhages and localized necrotic areas on day 1, which
transformed to areas of cavitation and fibrinoid necrosis surrounded by a
demarcating rim of numerous astrocytes by day 7. The mean percentage of area of
GFAP expression increased significantly by day 7. Osmic acid staining revealed
swollen nerve fibers after one day, while numerous fibers had been lost by day 7.
An ultrastructure study revealed swollen redundant thinned myelin and myelin
splitting, as well as degeneration of axoplasm on day 1. On day 7, layers of the
myelin sheath were folded and wrinkled with partial or complete demyelination
areas. The myelin lamellae were disorganized and loose. The G-ratio was
significantly greater on day 1 than day 7 after CSCI. CONCLUSIONS: In the rat
model of CSCI details of the progressive spinal cord injury can be analyzed by
morphological methods and may be helpful in the identification of the onset and
type of clinical intervention.
PMID- 28509313
TI - Decreased expression of survivin 2B in human pituitary adenomas. A preliminary
study.
AB - INTRODUCTION: We aimed to investigate survivin and its splice variants DEx3 and
2B expressions in pituitary adenomas and normal pituitary glands using
immunohistochemistry. MATERIAL AND METHODS: The study group consisted of eight
pituitary adenomas: five of non-functional tumors, two of GH-secreting tumors,
and one PRL-secreting tumor. Eight healthy pituitary tissue samples obtained
after autopsy served as controls. RESULTS: Survivin expression was found in 87.5%
of the study group and 100% of the controls. A positive staining of survivin 2B
was found in 62.5% of pituitary adenomas and 100% of controls. Survivin DEx3 was
recognized in 25% of pituitary adenomas and 12.5% of normal pituitary glands.
There was significantly lower immunoreactivity of survivin 2B in pituitary
adenomas when compared with normal pituitary glands (p = 0.0498). CONCLUSIONS:
Survivin and its splice variants might be involved to some extent in benign tumor
growth of pituitary adenomas. However, survivin cannot be regarded as a candidate
for targeted therapy or molecular biomarker of pituitary adenomas.
PMID- 28509314
TI - Influence of oxygen concentration on T cell proliferation and susceptibility to
apoptosis in healthy men and women.
AB - INTRODUCTION: Much of what we know about the functioning of human T lymphocytes
is based on the experiments carried out in atmospheric oxygen (O2)
concentrations, which are significantly higher than those maintained in blood.
Interestingly, the gender differences in the activity of T cells and their
susceptibility to apoptosis under different O2 conditions have not yet been
described. The aim of the study was to compare two main markers of lymphocyte
function: proliferation capacity and ability to produce cytokines as well as
their susceptibility to apoptosis under two different O2 concentrations, between
men and women. MATERIALS AND METHODS: 25 healthy volunteers, both males (13) and
females (12) were recruited to the study (mean age 25.48 +/- 5.51). By using
cytometry proliferation parameters of human CD4+ CD28+ cells or CD8+CD28+ cells
in response to polyclonal stimulation of the TCR/CD3 complex at atmospheric (21%)
and physiological (10%) O2 concentrations using our modified dividing cell
tracking technique (DCT) were analyzed as well as the percentages of apoptotic
cells. We also determined the levels of IFN-gamma, IL-2, IL-10 and IL-17A using
Cytometric Bead Array Flex system in cell culture supernatants. RESULTS:
CD4+CD28+ and CD8+CD28+ cells from the whole study group were characterized by
shorter time required to enter the first (G1) phase of the first cell cycle at
21% compared to 10% O2. Both T cell populations performed significantly more
divisions at 21% O2. The percentages of dividing cells were also significantly
higher at atmospheric O2. Interestingly, data analysis by gender showed that male
lymphocytes had similar proliferative parameters at both O2 concentrations while
female lymphocytes proliferate more efficiently (note from the author: we cannot
say that lymphocytes proliferate faster, rather more effectively, because cells
perform more divisions, which gives more percentage of offspring cells) at 21%
oxygen. Compared to males, the female CD4+ cells showed increased susceptibility
to apoptosis at both O2 concentrations. No differences in the levels of cytokines
regardless of gender and oxygen conditions were found. CONCLUSIONS: We showed
that in vitro female T cells (both CD4+ and CD8+ cells) are more sensitive than
male lymphocytes to low O2 concentration as demonstrated by the decrease in their
proliferation dynamics. The effect does not depend on increased apoptosis of
female T cells under low O2 because percentage of apoptotic cells was similar at
both O2 concentrations.
PMID- 28509315
TI - Caspase-3 as an important factor in the early cytotoxic effect of nickel on oral
mucosa cells in patients treated orthodontically.
AB - INTRODUCTION: The effect of fixed orthodontic appliances on biochemical changes
in saliva and pathophysiological status of the oral cavity is not clear. Recent
data showed that nickel (Ni) released from orthodontic appliances can decrease
cellular viability, induce DNA damage and apoptosis in oral mucosa cells. Since
the mechanism of these Ni effects is unknown, the aim of our study was to analyze
the expression of caspase-3 in epithelial cells of oral mucosa in healthy
individuals treated orthodontically. MATERIAL AND METHODS: Twenty-eight
volunteers participated in the study. Epithelial cells were collected from oral
mucosa directly before appliance insertion, one week after the insertion, and 24
four weeks after the insertion of fixed appliances. Cellular identification and
measurements were conducted by light microscopy. Caspase-3 expression was
evaluated immunochemically. Nickel concentration in saliva was also determined.
RESULTS: A significantly higher number of oral epithelial cells with caspase-3
immunoreactivity in was found one week, but not 24 weeks, after orthodontic
treatment. The enhanced expression of caspase-3 was accompanied by increased
nickel concentration in saliva. CONCLUSIONS: Our data suggests that nickel
released from orthodontic appliances can activate caspase-3 and this mechanism
may be partially responsible for the cytotoxic action of nickel in the oral
cavity of orthodontically-treated individuals.
PMID- 28509316
TI - Effects of 17beta-estradioland raloxifene on endothelial OPG and RANKL secretion.
AB - OBJECTIVES: This study aims to asses the effects of estradiol vs. raloxifene on
the levels of osteoprotegerin and soluble Receptor Activator of Nuclear Factor kB
Ligand (sRANKL) in Human Umbilical Vein Endothelial Cells (HUVEC) culture in
standard and calcifying medium. MATERIAL AND METHODS: Human Umbilical Vein
Endothelial Cells were isolated from human umbilical vein by standard method. The
supernatant concentrations of osteoprotegerin (OPG) and sRANKL (ELISA) were
determined after incubation with glicerophosphate, estradiol , raloxifene,
glicerophoshate and estradiol, glicerophosphate and raloxifene in comparison with
control group at four designated time points (0, 1, 2 and 4 days of incubation).
RESULTS: Incubation of estradiol with HUVEC colony lowered the OPG level
significantly after day 2 and 4. Meantime, the level of sRANKL was stable.
Raloxifene added to standard growth medium also significantly lowered OPG
concentration after day 4 only, with no impact on sRANKL concentration. When
added to calcifying medium, both estradiol and raloxifene significantly changed
OPG level during the experiment. In all treated groups OPG levels were lower than
in groups exposed to calcifying medium only. Neither estradiol, nor raloxifene
changed sRANKL levels during the experiment. CONCLUSIONS: Estradiol and
raloxifene affect OPG secretion from endothelial cells in vitro which may suggest
their modifying role in pathogenesis of vascular calcification in postmenopausal
women.
PMID- 28509317
TI - Morphology of the cesarean section scar in the non-pregnant uterus after one
elective cesarean section.
AB - OBJECTIVES: A growing number of studies suggest that the incomplete healing of
the CS scar in the uterus increase the risk of uterine dehiscence or rupture
during subsequent pregnancies. Thus, the factors that affect wound healing should
be evaluated. We aimed to determine whether the morphology of the CS scar in non
pregnant women after one elective CS was affected by the site of the uterine
incision, uterine flexion, maternal age, and fetal birth weight. MATERIAL AND
METHODS: 208 non-pregnant women were invited for participation in the study, but
only 101 of them met inclusion criteria. Standardized scar parameters (residual
myometrial thickness (RMT), depth (D) and width (W) of the hypoechoic niche) were
measured using ultrasonography at least 6 weeks after the CS. RESULTS: Scar
defect was detected in 26 of 101 subjects. Women without scar defect had
significantly higher RMT values (1.87 vs. 0.87), lower newborn birth weight (3127
g vs. 3295 g), and higher scar location above the internal cervical os (62% vs.
16%), than those with scar defect. Maternal age was significantly correlated with
D value (R = 0.40). Uterine retroflexion was significantly correlated with a
larger D value (R = 0.63) and a larger D/RMT ratio (R = 0.24). CONCLUSIONS: In
low-risk women who have undergone one elective CS, several risk factors are
associated with development of the scar defect, but only scar location can be
modified during surgery. Future research is needed to determine whether a
relatively higher incision location in the uterus can ensure optimal healing of
the CS scar.
PMID- 28509318
TI - The duration of pregnancy in ecologically-challenged area. The effects of
environmental pollution with aromatic hydrocarbons on the angiogenesis and
elements of the mesenchymal tissue of the human placenta.
AB - INTRODUCTION: The literature presents only few reports regarding the effects of
elevated levels of aromatic hydrocarbons (AH) on the functions of the human
placenta. The effects of environmental contamination with AH (including phenol
and 1-hydroxypyrene) have certain negative effects on parenchymal organs such as
human placenta. OBJECTIVE: The paper aimed to assess the effects of elevated
levels of AH on the placental angiogenesis and elements of the mesenchymal tissue
of the placenta. MATERIAL AND METHODS: Tissue material from 50 afterbirths from
Plock constituted a study group, whereas 50 afterbirths from Kutno constituted a
control group. Immunohistochemical reactions with the peroxidase method using
LSAB kits (DAKO) were performed. The extent and intensity of reactions were
analysed. The levels of phenols and 1-hydroxypyrene in the excreted urine of
pregnant women (undergoing delivery) were detected using gas chromatography and
colorimetry. RESULTS: The levels of phenol and 1-hydroxypyrene in the excreted
urine were demonstrated to be statistically significantly higher in patients
living in the area of Plock. Statistically significantly higher expression of
antibodies indicating placental angiogenesis was observed in the placentas in the
Plock group (p < 0.01). Moreover, lower expression of vimentin indicating
reactions with proteins in mesenchymal cells was observed in the Kutno group (p <
0.01). CONCLUSIONS: Pregnancy in the environment with elevated levels of aromatic
hydrocarbons has detrimental effects on the human placenta. The foetus is
protected by activation of adaptation and compensation mechanisms that are
manifested as significant angiogenesis and greater development and
differentiation of mesenchymal cells compared to the control group.
PMID- 28509319
TI - Investigation of cesarean sections at Konya Training and Research Hospital
Obstetrics and Gynecology Department between 2010 and 2015.
AB - OBJECTIVE: Analysis of the annual distribution of cesarean sections and
indications between 2010 and 2015 in our clinic. MATERIAL AND METHODS: Medical
records of 10,437 cesarean section patients from a total number of 24,283
deliveries performed at Department of Obstetrics and Gynecology between 2010-2015
were evaluated retrospectively. The indications for Cesarean section were
analyzed and compared based on years. RESULTS: The lowest cesarean section rate
was 18.67% in 2011 and the highest rate was 24.5% in 2013, and the annual rates
were close to each other in this 6-year period (p > 0.05). History of uterine
surgery was the indication with the highest rate of 49.52%, while fetal distress
was the second most frequent with 12.53%; presentation anomalies were observed as
the most frequent third indication with 7.55%, and umbilical cord prolapse was
the least frequent indication with 0.33%. CONCLUSIONS: Patient education about
normal delivery and providing means for pain control during normal delivery,
improvement in physical conditions of the clinics, frequent and regular training
of the assisting staff with obstetrics physicians are important to diminish the
rates of primary cesarean sections. In addition, a normal delivery after a
previous cesarean section must be encouraged.
PMID- 28509320
TI - Premature fetal tissues are possible source of valuable mesenchymal stem cells.
AB - OBJECTIVES: Comparison of the ability to inhibit alloactivated lymphocytes
proliferation of human Wharton Jelly (WJ) and amniotic membrane (AM) mesenchymal
stem cells (MSCs) from preterm and term pregnancies. MATERIAL AND METHODS: Term
WJ-MSCs (n = 5) and Preterm-WJ-MSCs (n = 1) were obtained from tissue explants by
adherent method. Term-AM-MSCs (n = 5) and Preterm-AM-MSCs (n = 1) were obtained
by tripsin and collagenase digestion method. Term and Preterm MSCs phenotype was
confirmed in vitro by flow cytometry. To evaluate the potential of fetal and
adult MSCs to diminish immunological response mixed lymphocytes reaction (MLR)
has been performed. RESULTS: Term and Preterm cells were positively identified as
MSCs by the expression of CD73 and CD90 and CD105 with simultaneous absence of
CD11b, CD14, CD19, CD34, CD45 and HLA-DR. The mean inhibition of allostimulated
lymphocytes after addition of fetal derived MSCs amounted 64.8% for term AM-MSCs
and 42.1% for term WJ-MSCs (for both populations the effect was statistically
significant, p < 0.01). The addition of preterm-MSCs to MLR resulted in reduction
of stimulated lymphocytes proliferation by 64.9% for AM-MSCs and 86.1% for WJ
MSCs. CONCLUSIONS: Presented results suggest that preterm fetal tissues contain
MSCs which posses similar immunosuppressive capacity as those from term
pregnancies. In the future MSCs from the umbilical cord and amnion can be
potentially used to prevent immuno-dependent injuries in premature newborns.
PMID- 28509321
TI - Evaluation of tissue metalloproteinase inhibitor TIMP-1 and Survivin levels
during third trimester pregnancy - a preliminary report.
AB - OBJECTIVES: A proper implantation of trophoblastic cells and an appropriate
metalloproteinases activity is required to cause disintegration of basal
membranes of cells. The activity of tissue matrix metaloproteinases can be
inhibited by their matrix inhibitors - TIMP-s. Survivin is a member of inhibitor
of apoptosis proteins family (IAP), that suppresses caspase activation,
influences VEGF expression and promotes proliferative action of endothelial
cells. MATERIAL AND METHODS: The aim of the study was to assess concentrations of
two independent anti-apoptotic factors. TIMP-1 and survivin in serum of women in
their third trimester of pregnancy and in umbilical cord blood of neonates -
drawn separately from veins and arteries. The study group consisted of 29
pregnant women in physiological pregnancy and with correct fetal development, in
gestational age between 37 to 40 weeks of gestation. Blood used in the study was
collected from maternal cubital fossa veins and from neonatal umbilical cords
(from veins and from arteries separately). The research was conducted using TIMP
1 and Survivin ELISA kits from R & D Systems according to manufacturers'
recommendations and protocols. RESULTS: The concentrations of TIMP-1 were similar
and independent of the source of blood samples. Arterial values of TIMP-1 in
umbilical cord compared to maternal and fetal veins were slightly lower, but no
statistical difference was found. The mean concentrations of Survivin were
comparable but we found that in some cases the results in cord blood serum in
both vessels-vein and arteries were almost negative. Arterial values of Survivin
in umbilical cord compared to maternal blood were higher, but no statistical
difference was found. CONCLUSIONS: In III-rd trimester of pregnancy parameters of
Timp-1 and Survivin - anti-apoptotic substances concentration were similar in
maternal and cord blood in both artery and vein. We found no increased activity
of selected antiapoptotic factors.
PMID- 28509322
TI - Polymorphic variants of genes involved in choline pathway and the risk of
intrauterine fetal death.
AB - OBJECTIVES: Choline and folate metabolism disturbances may be involved in the
occurrence of intrauterine fetal death (IUFD). The proper activity of this
metabolism could be determined by genetic variants involved in choline pathway
e.g. CHKA (gene encoding choline kinase alpha), PCYT1A (gene encoding CCTalpha)
and CHDH (gene encoding choline dehydrogenase). Our study aimed at determining
the genotype and allele frequencies of CHKA rs7928739, PCYT1A rs712012, PCYT1A
rs7639752, CHDH rs893363 and CHDH rs2289205 polymorphisms in mothers with IUFD
occurrence. MATERIAL AND METHODS: The study involved 76 mothers with IUFD
occurrence and 215 mothers of healthy children. Genetic analysis was performed
with the use of PCR/RFLP method. RESULTS: The frequency of genotypes and alleles
of studied polymorphisms was similar in both groups. The study revealed no
association of PCYT1A, CHKA and CHDH polymorphisms in analysed groups of women.
While evaluating the co-existence of analysed polymorphisms statistically
significant correlation was revealed. Co-existence of CHKA rs7928739 AC/CHDH
rs2289205 AA genotypes was observed statistically more frequently in the study
group than in the control group (p = 0,031). CONCLUSIONS: There is no correlation
between single CHKA rs7928739, PCYT1A rs712012, PCYT1A rs7639752, CHDH rs893363
and CHDH rs2289205 polymorphisms and the incidence of intrauterine fetal death.
However, revealed statistically significant difference between co-existence of
CHKA rs7928739 AC/CHDH rs2289205 AA genotypes between study groups suggest the
need of further analysis.
PMID- 28509323
TI - Triple negative endometrial cancer.
AB - Endometrial cancer (EC) is the most common malignancy of the female genital tract
in the developed countries. In Poland, EC incidence increased from 3.496 to 5.251
between 2000 and 2011, with 5.251 new cases were diagnosed in 2011 alone, and
this upward trend is expected to continue. There are two types of endometrial
cancer: estrogen- related type I (approximately 80% of the cases) and unrelated
to estrogen type II. Type I includes adenocarcinomas which grow slowly, have
better prognosis, superficially infiltrate the myometrium, originate from
endometrial hyperplasia without atypia, and occur before and after menopause. The
most common type I mutations include PTEN, KRAS and microsatellite instability.
Type II is represented by serous, mucinous, clear-cell carcinomas, with
aggressive behavior associated with poor prognosis, high risk of distant
metastases at diagnosis, deeper infiltration of the uterine muscle, often to
serosa, originating from the atrophic endometrium, and typically presenting after
menopause. The most common type II mutations include TP53, HER-2 and P16.
PMID- 28509324
TI - Three-dimensional neurosonography - a novel field in fetal medicine.
AB - Neurosonography is a promising technique for prenatal diagnosis, combining
features of ultrasound imaging with fetal neurology. The brain is a three
dimensional structure, therefore observing brain structure in the three basic
planes (sagittal, coronal and axial) is mandatory. The anterior fontanelle and
sagittal suture may serve as acoustic ultrasound windows in the transvaginal
brain scan, allowing to obtain high-resolution neuroimages of the intracranial
structures. Furthermore, three-dimensional (3D) ultrasound combined with the
transvaginal brain approach provides detailed and sophisticated neuroimages.
Three orthogonal planes of the brain, tomographic ultrasound imaging (TUI) and
other off-line approaches (e.g. volume contrast imaging (VCI) or HDlive
silhouette imaging) may be obtained from a single 3D dataset. 3D Doppler
ultrasound enables visualization of the intracerebral vascularity, allowing to
obtain more precise information on cerebral perfusion. Various abnormal brain
conditions, including ventriculomegaly, agenesis of the corpus callosum,
posterior fossa abnormalities and others, can be well-demonstrated. Due to high
rates of the associated anomalies and uncertain prognosis, any suspicion of CNS
abnormalities shall imply detailed ultrasonographic evaluation of the fetal
anatomy to exclude the associated anomalies. Despite a growing number of
neuroimaging modalities, prenatal counselling remains a challenge as prediction
of brain functionality and the neurological prognosis often remain uncertain. New
investigations on the relations between various migration disorders and gene
mutations, as well as recent clinical research on the relations between
neuroimaging detection of local migration disorders using sophisticated imaging
technologies and the postnatal neurological prognosis will contribute to the
development of maternal-fetal medicine as well as pediatric neurology.
PMID- 28509325
TI - An alternative approach to gynecological wound healing.
AB - An 89-year-old woman was reffered to our Clinic with vulvar cancer. She also
suffered from obesity [with body mass index (BMI) 35 kg/m2], persistent
hypertension, diabetes mellitus type 2 treated with oral medications. In 2015 she
underwent a surgery due to endometrial carcinoma. Total abdominal hysterectomy
with bilateral salphingoophorectomy, omentectomy and pelvical node dissection was
performed (histopathology revealed adenocarcinoma serosum G2; FIGO stage Ib). In
January 2016 after vulvar ulceration biopsy plano-epithelial squamous vulvar
cancer was diagnosed. She was referred to surgery. She has undergone an operation
in October 2016. She was admitted to gynaecological unit at our institution.
Physical examination revealed mutilated vulva with excised labia major, labia
minor, and narrowing of vaginal orifice. The right side shown tumor 2.5 cm in
diameter, with slough area and no deep infiltration and satellital nodule on the
left labia majora 1cm in diameter. The cervix, vaginal wall, rectum and anus
appeared normal. There were no enlarged lymph nodes at the inguinal area.
PMID- 28509326
TI - Polish Gynecological Society Recommendations for Labor Induction.
AB - Labor induction involves artificial stimulation of childbirth before the natural,
spontaneous onset of labor. It is one of the most common procedures in modern
obstetrics. The frequency of labor induction has doubled in recent decades due to
the development of perinatology and methods of monitoring fetal well-being in
particular. Currently, one in five pregnant women and 30-40% of women delivering
vaginally undergo this procedure. Reasons for induction include reduction of the
perinatal mortality and morbidity of the fetus and newborn, as well as the
reduction of maternal complications. However, as every medical intervention,
labor induction is associated with a risk of complications.
PMID- 28509327
TI - The occurrence of hepatocellular carcinoma in different risk stratifications of
clinically noncirrhotic nonalcoholic fatty liver disease.
AB - Nonalcoholic fatty liver disease (NAFLD) may be a cause of hepatocellular
carcinoma (HCC), but its high prevalence challenges current surveillance
strategies. We aimed to evaluate HCC incidences in different risk stratifications
for noncirrhotic NAFLD. Using Taiwan's National Health Insurance Research
Database, we located 31,571 patients with NAFLD between the years 1998 and 2012.
After excluding other causes of hepatitis, underlying cirrhosis or malignancy,
18,080 patients were recruited for final analysis. Cumulative incidences of HCC
were analyzed after adjusting for competing mortality. With a median follow-up
duration of 6.32 years in the study cohort, the 10-year cumulative incidence of
HCC was 2.73% [95% confidence interval (CI): 1.69-3.76%]. Hepatoprotectant was
used as a surrogate marker for elevated serum alanine transaminase (ALT). After
adjusting for age, gender, hypertension, hypercholesterolemia, diabetes mellitus,
gout, statin use, metformin use and aspirin use, elevated ALT was independently
associated with an increased HCC risk [hazard ratio (HR) 6.80, 95% CI: 3.00
15.42; p < 0.001]. Multivariate stratified analysis verified this association in
all subgroups (HR> 1.0). Moreover, increased age (HR 1.08 per year, 95% CI: 1.05
1.11) and statin use (HR 0.29, 95% CI: 0.12-0.68) were also identified as
independent risk factors. The 10-year cumulative HCC incidence was highest in
older (age >55 years) patients with ALT elevation (12.41%, 95% CI: 5.99-18.83%),
but lowest in younger patients without ALT elevation (0.36%, 95% CI: 0-1.08%).
The incidence of HCC was relatively low in patients with clinically noncirrhotic
NAFLD, however, HCC risk was significantly increased in older patients
experiencing an elevated serum ALT.
PMID- 28509328
TI - Anatomy-based DMEK Wetlab in Homburg/Saar: Novel aspects of donor preparation and
host maneuvers to teach descemet membrane endothelial keratoplasty.
AB - Use of Descemet Membrane Endothelial Keratoplasty (DMEK) has been limited because
of problems with donor preparation, i.e. tearing of the Descemet membrane and
difficulties in unfolding the Endothelium-Descemet-Membrane-Layer (EDML) in the
anterior chamber (AC). The purpose of this work was to describe a novel approach
to teaching anatomy-based donor and recipient preparation in a DMEK-Wetlab. We
teach successful mono-manual donor preparation of human corneas in organ culture
not suitable for transplantation, including peripheral markers for orientation.
We also teach safe recipient preparation in a freshly-enucleated pig eye in organ
culture preservation medium for atraumatic introduction of the EDML roll into the
AC, reliable orientation of the EDML during surgery, and stepwise unfolding
within the AC. Twenty-two candidates in the 1. Homburg Cornea Curriculum HCC 2015
who practiced both preparations using three human donor corneas and three pig
eyes assessed the procedure as follows: (1) overall grade of the Wetlab 1.4
(median 1, range 1 to 2 - on a scale from 1 (excellent) to 6 (terrible); (2) most
participants and tutors stated that the Wetlab is most effective for colleagues
who have some previous experience with corneal microsurgery. Our novel anatomy
based approach to simulating donor preparation and graft implantation for DMEK
seems to meet the expectations and requirements of colleagues with previous
experience in corneal microsurgery and will help to reduce the rate of
complications for incipient DMEK surgeons in the future. Clin. Anat. 31:16-27,
2018. (c) 2017 Wiley Periodicals, Inc.
PMID- 28509329
TI - A case of combined desmoplastic trichoepithelioma and compound melanocytic nevus.
PMID- 28509330
TI - Malignancies in hepatitis C virus-positive and -negative kidney transplant
recipients: A case-controlled study.
AB - BACKGROUND: Malignancies and lymphoma are common complications after kidney
transplantation. However, no link has been made between the incidence of
malignancies and hepatitis C virus (HCV) infection in this setting. This case
controlled study compared the incidence of malignancies, including lymphoma,
between kidney transplant (KT) patients with or without HCV replication. PATIENTS
AND METHODS: A total of 99 HCV-positive RNA-positive KT patients were matched
with 198 (1:2) anti-HCV-negative patients according to age, gender, and date of
transplantation, and were followed for 145.8+/-78.4 months. RESULTS: During the
follow-up period, 28 HCV-positive (28%) cases developed at least one cancer, and
64 (32%) patients developed cancer in the HCV-negative group (P=not significant
[ns]). Survival without a cancer was similar between both groups. Thirteen HCV
positive patients (13%) developed at least one solid cancer vs 29 (15%) HCV
negative patients (P=ns). Survival without a solid cancer was similar between
both groups. Three patients from the HCV-positive and 4 from the HCV-negative
group developed a lymphoma. Only 2 patients from the HCV group died from
hepatocellular carcinoma. Survival without a skin cancer was similar between both
groups. Patient and death-censored graft survival rates were significantly lower
in the HCV group. CONCLUSION: The incidences and types of malignancies were
similar in the HCV-positive and HCV-negative KT patients.
PMID- 28509331
TI - Anatomic landmarks in lacrimal surgery from an ophthalmologist's point of view:
Clinical findings of external dacryocystorhinostomy and dacryoendoscopy.
AB - Epiphora is a common clinical symptom of nasolacrimal duct obstruction. However,
it is present in several pathologies and can lead to decreased quality of life
for patients. A careful clinical examination including a detailed patient's
history and diagnostic tests such as the fluorescein dye disappearance test and
diagnostic syringing of the lacrimal duct are essential. Depending on the time of
presentation (congenital, primary, or secondary acquired), grade (subtotal or
total) and location of the stenosis, different surgical approaches can be
considered. These are subdivided into minimally invasive (transcanalicular) and
anastomosing (dacryocystorhinostomy) procedures. Furthermore, the anatomical
landmarks and the site of surgical intervention differentiate the surgical
techniques into endoscopic or transcutaneous. Modern intubation techniques offer
a large spectrum of therapeutic possibilities enabling patient care to be
customized and individualized. Knowledge of the topographical anatomy is crucial
for achieving greater success and a lower complication rate. Clin. Anat. 30:1034
1042, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28509334
TI - Enantioselective Synthesis of Tetrahydroquinolines by Borrowing Hydrogen
Methodology: Cooperative Catalysis by an Achiral Iridacycle and a Chiral
Phosphoric Acid.
AB - We report herein the highly enantioselective synthesis of 2-substituted
tetrahydroquinolines through borrowing hydrogen, a process recognized for its
environmentally benign and atom-economical nature. The use of an achiral
iridacycle complex in combination with a chiral phosphoric acid as catalysts was
the key to the development of this highly efficient and enantioselective
transformation.
PMID- 28509332
TI - Myeloid but not epithelial tissue factor exerts protective anti-inflammatory
effects in acid aspiration-induced acute lung injury.
AB - : Essentials Tissue factor (TF) represents a central link between hemostasis and
inflammation. We studied the roles of myeloid and airway epithelial TF in acid
caused acute lung injury (ALI). TF on myeloid cells displays a non-coagulatory
role regulating the inflammatory response in ALI. Airway epithelial TF
contributes to hemostatic functions, but is dispensable in ALI pathogenesis.
SUMMARY: Introduction Acute lung injury (ALI) is a life-threatening condition
characterized by damaged alveolar-capillary structures and activation of
inflammatory and hemostatic processes. Tissue factor (TF) represents a crucial
link between inflammation and coagulation, as inflammatory mediators induce
myeloid TF expression, and TF initiates extrinsic coagulation. Objective As
pulmonary inflammation stimulates TF expression and TF modulates immune
responses, we aimed to elucidate its impact on ALI. In particular, we wanted to
distinguish the contributions of TF expressed on airway epithelial cells and TF
expressed on myeloid cells. Methods Mice with different cell type-specific TF
deficiency and wild-type littermates were intratracheally treated with
hydrochloric acid, and leukocyte recruitment, cytokine levels, thrombin
antithrombin (TAT) complexes and pulmonary protein-rich infiltrates were
analyzed. Results Our data demonstrate that a lack of epithelial TF did not
influence acute responses, as bronchoalveolar neutrophil accumulation 8 h after
ALI induction was unaltered. However, it led to mild, prolonged inflammation, as
pulmonary leukocyte and erythrocyte numbers were still increased after 24 h,
whereas those in wild-type mice had returned to basal levels. In contrast,
myeloid TF was primarily involved in regulating the acute phase of ALI without
affecting local coagulation, as indicated by increased bronchoalveolar neutrophil
infiltration, pulmonary interleukin-6 levels, and edema formation, but equal TAT
complex formation, 8 h after ALI induction. This augmented inflammatory response
associated with myeloid TF deficiency was confirmed in vitro, as
lipopolysaccharide-stimulated TF-deficient alveolar macrophages released
increased levels of chemokine (C-X-C motif) ligand 1 and tumor necrosis factor
alpha as compared with wild-type macrophages. Conclusion We conclude that myeloid
TF dampens inflammation in acid-induced ALI.
PMID- 28509335
TI - Dignity-conserving care actions in palliative care: an integrative review of
Swedish research.
AB - BACKGROUND: Previous research has proposed that persons in need of palliative
care often have a loss of functions and roles that affects social and existential
self-image. Moreover, these individuals also commonly suffer from complex
multisymptoms. This, together with the situation of facing an impending death,
can lead to a loss of dignity. Therefore, supporting these persons' dignity is a
crucial challenge for professional nurses. The 'Dignity Care Intervention'
addresses the multidimensionality of dignity by identifying patients' dignity
related concerns and suggests care actions to address them. At the present, the
Dignity Care Intervention is adapted for implementation in Swedish care settings.
Because expressions of dignity are influenced by culture, and an overview of care
actions in a Swedish context is lacking, this integrative review aimed to find
suggestions from Swedish research literature on what kind of care actions can
preserve dignity. METHODS: An integrative literature review was conducted using
the databases SwePub and SweMed+. Articles published from 2006 to 2015 and theses
published from 2000 to 2015 were searched for using the terms 'dignity' and
'palliative care'. Result sections of articles and theses were reviewed for
dignity-conserving care actions synthesised by thematic analysis and categorised
under themes and subthemes in Chochinov's model of dignity. RESULTS: Fifteen
articles and 18 theses were included together providing suggestions of care
actions in all themes and subthemes in the dignity model. Suggested care actions
included listening, communication, information, symptom control, facilitating
daily living and including patients in decision-making. Additionally, nurses'
perceptiveness towards the patients was a core approach. CONCLUSION: The review
offers culturally relevant suggestions on how to address specific dignity-related
concerns. The adapted Dignity Care Intervention will be a way for Swedish nurses
to provide person-centred palliative care that will conserve patients' dignity.
PMID- 28509333
TI - Altered glycan accessibility on native immunoglobulin G complexes in early
rheumatoid arthritis and its changes during therapy.
AB - The goal of this study was to investigate the glycosylation profile of native
immunoglobulin (Ig)G present in serum immune complexes in patients with
rheumatoid arthritis (RA). To accomplish this, lectin binding assays, detecting
the accessibility of glycans present on IgG-containing immune complexes by
biotinylated lectins, were employed. Lectins capturing fucosyl residues (AAL),
fucosylated tri-mannose N-glycan core sites (LCA), terminal sialic acid residues
(SNA) and O-glycosidically linked galactose/N-acetylgalactosamine (GalNac-L) were
used. Patients with recent-onset RA at baseline and after 3-year follow-up were
investigated. We found that native IgG was complexed significantly more often
with IgM, C1q, C3c and C-reactive protein (CRP) in RA patients, suggesting
alterations of the native structure of IgG. The total accessibility of fucose
residues on captured immune complexes to the respective lectin was significantly
higher in patients with RA. Moreover, fucose accessibility on IgG-containing
immune complexes correlated positively with the levels of antibodies to cyclic
citrullinated peptides (anti-CCP). We also observed a significantly higher
accessibility to sialic acid residues and galactose/GalNAc glyco-epitopes in
native complexed IgG of patients with RA at baseline. While sialic acid
accessibility increased during treatment, the accessibility of galactose/GalNAc
decreased. Hence, successful treatment of RA was associated with an increase in
the SNA/GalNAc-L ratio. Interestingly, the SNA/GalNAc-L ratio in particular rises
after glucocorticoid treatment. In summary, this study shows the exposure of
glycans in native complexed IgG of patients with early RA, revealing particular
glycosylation patterns and its changes following pharmaceutical treatment.
PMID- 28509336
TI - Application of the movement disorder society prodromal Parkinson's disease
research criteria in 2 independent prospective cohorts.
AB - BACKGROUND: The research criteria for prodromal PD of the MDS propose a new
approach for the assessment of the individual probability of prodromal PD. These
criteria require a testing of their reliability in different prospective cohorts.
OBJECTIVES: The objective was to evaluate the MDS prodromal PD criteria in 2
independent prospective studies. METHODS: Prodromal PD probabilities of the
Tubingen Evaluation of Risk Factors for Early Detection of Neurodegeneration
cohort (TREND study, n = 650, recruited by the presence of probable rapid eye
movement sleep behavior disorder, depression, and/or hyposmia or none of these at
baseline and 2-, 4-, and 6-year follow-up) and the population-based Prospective
Evaluation of Risk Factors for Idiopathic Parkinson's Syndrome cohort (PRIPS
Tubingen subsample; n = 715, baseline and 3- and 5-year follow-up) were
calculated. Baseline posttest probabilities, time to PD diagnosis, marker
constellations, and longitudinal changes of prodromal PD probabilities were
analyzed. RESULTS: Incident PD cases (TREND, n = 10; PRIPS = 7) showed
significantly higher likelihood ratios of risk and prodromal markers at baseline
when compared with nonconverters. Only 2 of 17 incident PD cases met the criteria
for probable prodromal PD (ie, posttest probability > 80%) and 5 had possible
prodromal PD (ie, > 50%) 1.4 to 3.8 years before diagnosis. The criteria showed
high specificity and negative predictive values (>98%), but low sensitivity
(TREND, 30%; PRIPS, 14%) and positive predictive values (TREND, 19%, PRIPS, 50%).
The individual risk for prodromal PD in incident PD cases showed an inverse
correlation with the time to conversion (Spearman rho = .80, P = .006) and unlike
in nonconverters, increased during follow-up. CONCLUSION: The MDS prodromal
criteria provide a practical framework for the calculation of prodromal PD risk.
Although specificity of the criteria is high, most patients will not meet the
criteria before diagnosis unless testing is thoroughly performed with numerous
and highly specific markers objectively assessed. (c) 2017 International
Parkinson and Movement Disorder Society.
PMID- 28509337
TI - Impact of induction chemotherapy, hyperfractionated accelerated radiotherapy and
high-dose thiotepa on brain volume loss and functional status of children with
primitive neuroectodermal tumour.
AB - BACKGROUND: The introduction of aggressive chemo-radiotherapy regimens has
improved overall survival in children with primitive neuroectodermal tumours
(PNET). However, these combinations may result in neurotoxicity. Previously
reported magnetic resonance imaging abnormalities in children receiving intensive
sequential chemotherapy, hyperfractionated accelerated radiotherapy (HART) and
high-dose thiotepa prompted us to investigate the degree of brain volume loss and
patients' functional status after therapy. METHODS: We retrospectively reviewed
clinico-radiological data of children with PNET treated in this way at our
centre. RESULTS: We studied 14 children treated between December 2009 and April
2013. Data were not complete for one child. Performance status was severely
restricted in four children, and mildly to moderately impaired in 7 of the 13
children. Eleven of 13 children showed mild-to-severe generalised
neuroparenchymal atrophy, in 7 of whom neuroparenchymal volume loss was moderate
to severe. Of these seven, six had received high-dose thiotepa. There was no
correlation between brain volume loss and Lansky performance status. However,
unexpected neurotoxicities, such as symptoms of transverse myelitis, were
observed. CONCLUSION: Measurement of brain volume loss in patients treated with
HART and high-dose thiotepa may not be sufficient to predict function. However,
correlation of brain volume loss due to late neurotoxicity with performance
decline may be more obvious over longer period of follow-up. The combination of
HART and myeloablative courses of thiotepa is associated with severe
neurotoxicity and subsequent decline in performance status in a significant
proportion of patients.
PMID- 28509338
TI - Investigation of the ischioanal fossa: Application to abscess spread.
AB - The location of perianal abscesses and the course of the fistula follow certain
patterns, especially in the relationship between external and internal openings.
However, it is still not clear how the contents of the ischioanal fossa,
especially the fibrous network of fat tissue, affect the route for such diseases.
Ten male adult cadavers were selected for the study. Seven horizontal transverse
section planes from 1 cm above the pubic symphysis to the inferior border of the
lesser trochanter of the femur were recorded after P45 sheet plastination. We
observed characteristics of fiber distribution in the ischioanal fossa and its
relationship with surrounding structures in every plane. There was a dense strip
type fiber connecting with junction fascia between the obturator internus and
gluteus maximus muscles. Close to the levator ani, obturator internus, and
gluteus maximus, the fibers were very dense and continuous with the fascia on the
surfaces of these three muscles. The function of the fibrous network was
considered to be not only the support of fat tissue in the fossa but also
cushioning during physiological actions such as defecation. We hope that these
morphological results could help to elucidate the passage of fistulae and the
locations susceptible to perianal abscesses. Clin. Anat. 30:1029-1033, 2017. (c)
2017 Wiley Periodicals, Inc.
PMID- 28509341
TI - The US cancer moonshot-A need and opportunity for primary care participation and
collaboration.
PMID- 28509339
TI - Comparison of JAK2V617F -positive essential thrombocythaemia and early primary
myelofibrosis: The impact of mutation burden and histology.
AB - An accurate histological diagnosis may distinguish essential thrombocythaemia
(ET) from early primary myelofibrosis (early-PMF), which is associated with worse
outcome. Outcome of ET is also negatively affected by the presence of the
JAK2V617F mutation. To investigate the impact of JAK2V617F mutation burden and
histology on outcome, we collected 475 WHO-diagnosed ET (69.2%) or early-PMF
JAK2V617F -positive patients followed in 4 Italian haematology centers. JAK2V617F
allele burden was <=50% in 90% and 87% of ET and early-PMF patients, respectively
(P = .34). During follow-up, 32 (9.7%) ET and 18 (12.3%) early-PMF patients
experienced 59 thrombotic events, and 27 patients (5.6%) and 6 (1.2%) patients
evolved to myelofibrosis and acute leukemia, respectively. At last contact, 28
(5.8%) patients had died. In early-PMF compared to ET, the 10-year mortality
rates (6.7% and 4.3%, P = .73), leukemic transformation rates (1.4% and 1.2%, P =
.45), and thrombosis rates (16.7% and 12.2%, P = .12) were comparable. Only
progression to overt myelofibrosis at 10 years was significantly worse (11.4% and
1.5%, P = .004). In multivariate analysis, a higher (>50%) JAK2V617F burden was
significantly correlated with fibrotic progression and histology. Considering
JAK2V617F -positive disease, a higher (>50%) JAK2V617F burden and histological
classification are independent prognostic risk factors for disease progression.
These findings reinforce the need for standardized detection of this mutation.
PMID- 28509340
TI - Platelet-rich fibrin-based matrices to improve angiogenesis in an in vitro co
culture model for bone tissue engineering.
AB - In the context of prevascularization strategies for tissue-engineering purposes,
co-culture systems consisting of outgrowth endothelial cells (OECs) and primary
osteoblasts (pOBs) have been established as a promising in vitro tool to study
regeneration mechanisms and to identify factors that might positively influence
repair processes such as wound healing or angiogenesis. The development of
autologous injectable platelet-rich fibrin (PRF), which can be generated from
peripheral blood in a minimal invasive procedure, fulfils several requirements
for clinically applicable cell-based tissue-engineering strategies. During this
study, the established co-culture system of OECs and pOBs was mixed with
injectable PRF and was cultivated in vitro for 24 h or 7 days. The aim of this
study was to analyse whether PRF might have a positive effect on wound healing
processes and angiogenic activation of OECs in the co-culture with regard to
proinflammatory factors, adhesion molecules and proangiogenic growth factor
expression. Histological cell detection revealed the formation of lumina and
microvessel-like structures in the PRF/co-culture complexes after 7 days of
complex cultivation. Interestingly, the angiogenic activation of OECs was
accompanied by an upregulation of wound healing-associated factors, as well as by
a higher expression of the proangiogenic factor vascular endothelial growth
factor, which was evaluated both on the mRNA level as well as on the protein
level. Thus, PRF might positively influence wound healing processes, in
particular angiogenesis, in the in vitro co-culture, making autologous PRF-based
matrices a beneficial therapeutic tool for tissue-engineering purposes by simply
profiting from the PRF, which contains blood plasma, platelets and leukocytes.
PMID- 28509342
TI - Morphological and molecular characterization of Bysmatrum subsalsum (Dinophyceae)
from the western Mediterranean Sea reveals the existence of cryptic species.
AB - Bysmatrum subsalsum is a cosmopolitan dinoflagellate species that inhabits marine
and transitional habitats. Despite its wide distribution, information on the
morphological variability, phylogeny and ecology of B. subsalsum is scarce. In
this study, we provide morphological and molecular data on B. subsalsum strains
and wild cells from different locations in the Mediterranean Basin. The dynamics
of cell abundances and the associated environmental conditions during a field
bloom are also described. Genetic sequences of B. subsalsum obtained in this
study showed large intraspecific differences, clustering in two well
differentiated clades. Despite a certain degree of variation with respect to cell
size, apical pore complex (APC) morphology and size, and cingulum displacement,
cells from the two clades showed similar morphological traits. These findings
indicated the occurrence of cryptic species. Comparisons of the morphology of our
B. subsalsum specimens with the few descriptions available in the literature
revealed larger than previously known intraspecific morphological variability.
Phylogenetic trees inferred from the concatenated SSU, 5.8S-ITS, and LSU rRNA and
the individual 5.8S-ITS regions suggested the inclusion of Bysmatrum in the
Peridiniales and a close phylogenetic relationship with Peridinium sensu stricto.
However, the low statistical support prevented the assignment of Bysmatrum to a
particular family of Peridiniales. Ecological data obtained from a bloom in La
Pletera salt marshes (Catalan Coast, Spain) suggested the species reaches high
cell abundances at water temperatures >20 degrees C and salinity levels >30. Our
results add new information regarding the morphology, phylogeny, and ecology of
B. subsalsum.
PMID- 28509343
TI - The influence of vascular risk factors on cognitive function in early Parkinson's
disease.
AB - OBJECTIVES: Hypertension, dyslipidemia, diabetes, and obesity are well
established risk factors for cognitive impairment and dementia in older adults.
In contrast, previous studies that have assessed the impact of vascular risk
factors (VRFs) on cognition in Parkinson's disease (PD) have had methodological
limitations and reported conflicting findings. We address this question in a
large well-characterized cohort of de novo PD patients. METHODS: A total of 367
untreated and non-demented patients aged 50 years and older with early PD (H&Y =
1.0-2.0) underwent a comprehensive clinical and neuropsychological assessment at
baseline and 24 months later. A series of linear mixed models were used to
determine the effects of VRFs on cognition while controlling for patient and
disease characteristics. The outcomes included norm-referenced Z-scores of global
cognition, visuospatial skills, verbal episodic memory, semantic verbal fluency,
attention, and working memory tests. RESULTS: A longer history of hypertension
and a higher pulse pressure were significant predictors of lower Z-scores on
immediate and delayed free recall, recognition, and verbal fluency tests. On
average, every 10 mmHg increase in pulse pressure was associated with a 0.08
reduction on the cognitive Z-scores. The effects were independent of age,
education, disease duration, motor impairment, medication, and depressive
symptoms. Other VRFs were not associated with cognitive outcomes. CONCLUSIONS:
Our results are consistent with previous studies suggesting that hypertension
exerts a detrimental effect on memory and verbal fluency in early PD. Management
of blood pressure and cardiovascular health may be important to reduce risk of
cognitive decline in PD. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28509345
TI - Early First-Trimester Transvaginal Sonographic Diagnosis of Maternal Ureterocele.
PMID- 28509344
TI - cGMP signaling inhibits platelet shape change through regulation of the RhoA-Rho
Kinase-MLC phosphatase signaling pathway.
AB - : Essentials Platelet shape change requires cytoskeletal rearrangement via myosin
mediated actin contraction. We investigated whether nitric oxide (NO) affected
thrombin-induced platelet shape change. NO inhibits shape change, RhoA/ROCK
signalling and myosin light chain (MLC) phosphorylation. NO promotes MLC
phosphatase activity, thus prevents MLC phosphorylation and shape change.
SUMMARY: Background Platelet shape change, spreading and thrombus stability
require activation of the actin cytoskeleton contractile machinery. The
mechanisms controlling actin assembly to prevent unwanted platelet activation are
unclear. Objectives We examined the effects of nitric oxide on the signaling
pathways regulating platelet actin-myosin activation. Results S
nitrosoglutathione (GSNO) inhibited thrombin-induced platelet shape change and
myosin phosphorylation of the myosin light chain (MLC). Because thrombin
stimulates phospho-MLC through the RhoA/ ROCK dependent inhibition of MLC
phosphatase (MLCP) we examined the effects of NO on this pathway. Thrombin caused
the GTP loading and activation of RhoA, leading to the ROCK-mediated
phosphorylation of MLCP on threonine 853 (thr853 ), which is known to inhibit
phosphatase activity. Treatment of platelets with GSNO blocked ROCK-mediated
increases in phosphoMLCP-thr853 induced by thrombin. This effect was mimicked by
the direct activator of protein kinase G, 8-pCPT-PET-cGMP, and blocked by the
inhibition of guanylyl cyclase, but not inhibitors of protein kinase A. Further
exploration of the mechanism demonstrated that GSNO stimulated the association of
RhoA with protein kinase G (PKG) and the inhibitory phosphorylation (serine188)
of RhoA in a cGMP-dependent manner. Consistent with these observations, in vitro
experiments revealed that recombinant PKG caused direct phosphorylation of RhoA.
The inhibition of RhoA by GSNO prevented ROCK-mediated phosphorylation and
inhibition of MLCP activity. Conclusions These data suggest novel crosstalk
between the NO-cGMP-PKG and RhoA/ROCK signaling pathways to control platelet
actin remodeling.
PMID- 28509346
TI - Role of quantitative p16INK4A mRNA assay and digital reading of p16INK4A
immunostained sections in diagnosis of cervical intraepithelial neoplasia.
AB - Visual interpretation of cervical biopsies is subjective and variable, generally
showing fair to moderate inter-reader agreement in distinguishing high from low
grade cervical intraepithelial neoplasia (CIN). We investigated the performance
of two objective p16 quantitative tests in comparison with visual assessment: (i)
p16-mRNA assay and (ii) digital analysis of sections stained for p16 protein. The
primary analysis considered 232 high-risk human papilloma virus positive (HPV+)
samples from diagnostic cervical specimens. A p16 RT-qPCR (p16-mRNA assay) was
run on mRNA extracted from formalin-fixed paraffin-embedded sections. Two p16
immunohistochemistry (IHC) readings, a visual read by a histopathologist (Visual
IHC) and a digital read of a high-resolution scan (Digital IHC), were done on
adjacent sections. The worst reviewed CIN grade (agreed by at least two
histopathologists) from up to two biopsies and a loop excision was taken, with
CIN2/3 as the primary endpoint. Visual IHC attained a specificity of 70% (95%CI
61-77) for 85% (95%CI 77-91%) sensitivity. The four-point Visual IHC staining
area under the curve (AUC) was 0.77 (95%CI 0.71-0.82), compared with 0.71 (95%CI
0.64-0.77) for p16-mRNA and 0.67 (95%CI 0.60-0.74) for Digital IHC. Spearman rank
order correlations were: visual to p16-mRNA 0.41, visual to digital 0.49 and p16
mRNA to digital: 0.22. The addition of p16-mRNA assay to visual reading of p16
IHC improved the AUC from 0.77 to 0.84 (p = 0.0049). p16-mRNA testing may be
complementary to visual IHC p16 staining for a more accurate diagnosis of CIN, or
perhaps a substitute in locations with a lack of skilled pathologists.
PMID- 28509348
TI - Reconstitution of the plant ubiquitination cascade in bacteria using a synthetic
biology approach.
AB - Ubiquitination modulates nearly all aspects of plant life. Here, we reconstituted
the Arabidopsis thaliana ubiquitination cascade in Escherichia coli using a
synthetic biology approach. In this system, plant proteins are expressed and then
immediately participate in ubiquitination reactions within E. coli cells.
Additionally, the purification of individual ubiquitination components prior to
setting up the ubiquitination reactions is omitted. To establish the
reconstituted system, we co-expressed Arabidopsis ubiquitin (Ub) and
ubiquitination substrates with E1, E2 and E3 enzymes in E. coli using the Duet
expression vectors. The functionality of the system was evaluated by examining
the auto-ubiquitination of a RING (really interesting new gene)-type E3 ligase
AIP2 and the ubiquitination of its substrate ABI3. Our results demonstrated the
fidelity and specificity of this system. In addition, we applied this system to
assess a subset of Arabidopsis E2s in Ub chain formation using E2 conjugation
assays. Affinity-tagged Ub allowed efficient purification of Ub conjugates in
milligram quantities. Consistent with previous reports, distinct roles of various
E2s in Ub chain assembly were also observed in this bacterial system. Therefore,
this reconstituted system has multiple advantages, and it can be used to screen
for targets of E3 ligases or to study plant ubiquitination in detail.
PMID- 28509347
TI - Domain-specific cognitive impairment in non-demented Parkinson's disease
psychosis.
AB - INTRODUCTION: In Parkinson's disease (PD), psychosis is associated with cognitive
impairment that may be more profound in particular cognitive domains. Our goal
was to determine whether psychosis in non-demented PD participants is associated
with domain-specific cognitive impairment on the Mini-Mental State Exam (MMSE).
METHODS: The Morris K. Udall Parkinson's Disease Research Center of Excellence
Longitudinal Study at Johns Hopkins is a prospective study that was initiated in
1998. Clinical assessments are conducted at two-year intervals at the Johns
Hopkins Hospital. We analyzed data from 137 enrolled participants with idiopathic
PD. Psychosis diagnoses were established by psychiatrist interview per DSM-IV
criteria. An incident dementia diagnosis resulted in exclusion from analysis for
that evaluation and any future evaluations in that participant. We used logistic
regression with generalized estimated equations (GEE) to model the time-varying
relationship between MMSE subscale scores and psychosis, adjusting for potential
confounding variables identified through univariable analysis. RESULTS: Thirty
one unique psychosis cases were recorded among non-demented participants. Fifty
total evaluations with psychosis present were analyzed. In multivariable
regressions, psychosis was associated with lower scores on the orientation
(relative odds ratio, rOR: 0.73; 95% CI: 0.58-0.93; p = 0.011), language (rOR:
0.64; 95% CI: 0.48-0.86; p = 0.003), and intersecting pentagon (rOR: 0.43; 95%
CI: 0.20-0.92 p = 0.030) subscales of the MMSE. CONCLUSIONS: In PD, executive
dysfunction, disorientation, and impaired language comprehension may be
associated with psychosis. Our findings suggest that the corresponding MMSE
subscales may be useful in identifying participants with a higher likelihood of
developing psychosis. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28509349
TI - Isolation of tissues and preservation of RNA from intact, germinated barley
grain.
AB - Isolated barley (Hordeum vulgare L.) aleurone layers have been widely used as a
model system for studying gene expression and hormonal regulation in germinating
cereal grains. A serious technological limitation of this approach has been the
inability to confidently extrapolate conclusions obtained from isolated tissues
back to the whole grain, where the co-location of several living and non-living
tissues results in complex tissue-tissue interactions and regulatory pathways
coordinated across the multiple tissues. Here we have developed methods for
isolating fragments of aleurone, starchy endosperm, embryo, scutellum, pericarp
testa, husk and crushed cell layers from germinated grain. An important step in
the procedure involves the rapid fixation of the intact grain to freeze the
transcriptional activity of individual tissues while dissection is effected for
subsequent transcriptomic analyses. The developmental profiles of 19 611 gene
transcripts were precisely defined in the purified tissues and in whole grain
during the first 24 h of germination by RNA sequencing. Spatial and temporal
patterns of transcription were validated against well-defined data on enzyme
activities in both whole grain and isolated tissues. Transcript profiles of genes
involved in mitochondrial assembly and function were used to validate the very
early stages of germination, while the profiles of genes involved in starch and
cell wall mobilisation matched existing data on activities of corresponding
enzymes. The data will be broadly applicable for the interrogation of co
expression and differential expression patterns and for the identification of
transcription factors that are important in the early stages of grain and seed
germination.
PMID- 28509350
TI - High sodium continuous veno-venous hemodialysis with regional citrate
anticoagulation and online dialysate generation in patients with acute liver
failure and cerebral edema.
AB - INTRODUCTION: Acute liver failure is associated with a high mortality rate.
Induction of plasma hypertonicity with mannitol or hypertonic saline remains the
cornerstone in the management of resultant cerebral edema. Significant
disadvantages of this approach include poor or unpredictable control of serum
sodium concentration and volume expansion, among others. METHODS: We used high
sodium continuous veno-venous hemodialysis with regional citrate anticoagulation
and online dialysate generation to accurately control the serum sodium in eleven
patients with acute liver failure, renal failure, and cerebral edema. We used a
Fresenius 2008 K/K2 machine in hemodialysis mode to deliver a blood flow of 60
ml/minute and dialysate flow of 400 ml/minute. Our previously published protocol
results in complete removal of infused citrate by the dialyzer. On-line clearance
calculations were used to model the time required to reach the target serum
sodium. FINDINGS: All patients achieved serum sodium within 2 mEq/L of target
without fluctuations or rebound. Nine patients survived without requiring liver
transplantation and two died despite reaching the prescribed serum sodium target.
We did not encounter any citrate toxicity. DISCUSSION: We describe a novel
approach for delivering continuous osmotherapy to patients with acute liver
failure, renal failure, and cerebral edema. In comparison to standard therapy,
the described modality enables precise titration of serum sodium without
undesirable fluctuations in extracellular fluid volume. A particular advantage is
zero delivery of citrate to this vulnerable group of patients with acute liver
failure.
PMID- 28509352
TI - Convergent mechanisms favor fast amyloid formation in two lambda 6a Ig light
chain mutants.
AB - Extracellular deposition as amyloids of immunoglobulin light chains causes light
chain amyloidosis. Among the light chain families, lambda 6a is one of the most
frequent in light chain amyloidosis patients. Its germline protein, 6aJL2, and
point mutants, R24G and P7S, are good models to study fibrillogenesis, because
their stability and fibril formation characteristics have been described. Both
mutations make the germline protein unstable and speed up its ability to
aggregate. To date, there is no molecular mechanism that explains how these
differences in amyloidogenesis can arise from a single mutation. To look into the
structural and dynamical differences in the native state of these proteins, we
carried out molecular dynamics simulations at room temperature. Despite the
structural similarity of the germline protein and the mutants, we found
differences in their dynamical signatures that explain the mutants' increased
tendency to form amyloids. The contact network alterations caused by the
mutations, though different, converge in affecting two anti-aggregation motifs
present in light chain variable domains, suggesting a different starting point
for aggregation in lambda chains compared to kappa chains.
PMID- 28509351
TI - A transcriptome-based assessment of the astrocytic dystrophin-associated complex
in the developing human brain.
AB - Astrocytes play a critical role in regulating the interface between the cerebral
vasculature and the central nervous system. Contributing to this is the
astrocytic endfoot domain, a specialized structure that ensheathes the entirety
of the vasculature and mediates signaling between endothelial cells, pericytes,
and neurons. The astrocytic endfoot has been implicated as a critical element of
the glymphatic pathway, and changes in protein expression profiles in this
cellular domain are linked to Alzheimer's disease pathology. Despite this, basic
physiological properties of this structure remain poorly understood including the
developmental timing of its formation, and the protein components that localize
there to mediate its functions. Here we use human transcriptome data from male
and female subjects across several developmental stages and brain regions to
characterize the gene expression profile of the dystrophin-associated complex
(DAC), a known structural component of the astrocytic endfoot that supports
perivascular localization of the astroglial water channel aquaporin-4.
Transcriptomic profiling is also used to define genes exhibiting parallel
expression profiles to DAC elements, generating a pool of candidate genes that
encode gene products that may contribute to the physiological function of the
perivascular astrocytic endfoot domain. We found that several genes encoding
transporter proteins are transcriptionally associated with DAC genes.
PMID- 28509354
TI - Single disease entity for both chromosomal instable subtype gastric
adenocarcinoma and esophageal adenocarcinoma.
AB - Gastric cardiac carcinoma (GCC) was and is considered as a part of esophageal
adenocarcinoma (EAC) and staged with the rules for EAC. This may change. Recent
comprehensive integrated genomic investigations on gastric and esophageal
carcinomas discovered similar chromosomal instability profiles in these two
groups of carcinomas with a gradual increasing gradient from the lowest
percentage in the distal gastric antrum to a high level in the proximal gastric
cardia, and to the peak of almost 100% in EAC. Therefore, most GCCs and EAC share
similar chromosomal instable features of gastric carcinoma and should be grouped
as a single disease entity because EAC may be the proximal extension of
chromosomal instable GCCs. This breakthrough discovery in genomic characteristics
of GCC and EAC would dramatically change the strategy on how patients should be
appropriately managed clinically and also greatly help future investigation on
detailed molecular pathogenetic mechanisms of GCC, leading to cure this fatal
cancer.
PMID- 28509353
TI - Engineering heat tolerance in potato by temperature-dependent expression of a
specific allele of HEAT-SHOCK COGNATE 70.
AB - For many commercial potato cultivars, tuber yield is optimal at average daytime
temperatures in the range of 14-22 degrees C. Further rises in ambient
temperature can reduce or completely inhibit potato tuber production, with
damaging consequences for both producer and consumer. The aim of this study was
to use a genetic screen based on a model tuberization assay to identify
quantitative trait loci (QTL) associated with enhanced tuber yield. A candidate
gene encoding HSc70 was identified within one of the three QTL intervals
associated with elevated yield in a Phureja-Tuberosum hybrid diploid potato
population (06H1). A particular HSc70 allelic variant was linked to elevated
yield in the 06H1 progeny. Expression of this allelic variant was much higher
than other alleles, particularly on exposure to moderately elevated temperature.
Transient expression of this allele in Nicotiana benthamiana resulted in
significantly enhanced tolerance to elevated temperature. An TA repeat element
was present in the promoter of this allele, but not in other HSc70 alleles
identified in the population. Expression of the HSc70 allelic variant under its
native promoter in the potato cultivar Desiree resulted in enhanced HSc70
expression at elevated temperature. This was reflected in greater tolerance to
heat stress as determined by improved yield under moderately elevated temperature
in a model nodal cutting tuberization system and in plants grown from stem
cuttings. Our results identify HSc70 expression level as a significant factor
influencing yield stability under moderately elevated temperature and identify
specific allelic variants of HSc70 for the induction of thermotolerance via
conventional introgression or molecular breeding approaches.
PMID- 28509355
TI - Lon protease modulates virulence traits in Erwinia amylovora by direct monitoring
of major regulators and indirectly through the Rcs and Gac-Csr regulatory
systems.
AB - Lon, an ATP-dependent protease in bacteria, influences diverse cellular processes
by degrading damaged, misfolded and short-lived regulatory proteins. In this
study, we characterized the effects of lon mutation and determined the molecular
mechanisms underlying Lon-mediated virulence regulation in Erwinia amylovora, an
enterobacterial pathogen of apple. Erwinia amylovora depends on the type III
secretion system (T3SS) and the exopolysaccharide (EPS) amylovoran to cause
disease. Our results showed that mutation of the lon gene led to the
overproduction of amylovoran, increased T3SS gene expression and the non-motile
phenotype. Western blot analyses showed that mutation in lon directly affected
the accumulation and stability of HrpS/HrpA and RcsA. Mutation in lon also
indirectly influenced the expression of flhD, hrpS and csrB through the
accumulation of the RcsA/RcsB proteins, which bind to the promoter of these
genes. In addition, lon expression is under the control of CsrA, possibly at both
the transcriptional and post-transcriptional levels. Although mutation in csrA
abolished both T3SS and amylovoran production, deletion of the lon gene in the
csrA mutant only rescued amylovoran production, but not T3SS. These results
suggest that CsrA might positively control both T3SS and amylovoran production
partly by suppressing Lon, whereas CsrA may also play a critical role in T3SS by
affecting unknown targets.
PMID- 28509356
TI - Assessments of pain in children and adolescents with cerebral palsy: a
retrospective population-based registry study.
AB - AIM: To explore pain screening in CPUP, a follow-up surveillance programme for
people with cerebral palsy (CP), specifically to describe reported pain
prevalence, localizations, patterns of distribution; to compare with studies
using psychometrically sound assessment instruments; and to assess agreement
between pain documented in CPUP and medical records. METHOD: Registry study of a
population with CP, born 1993 to 2008, living in Skane, Sweden in 2013.
Descriptive data, cross-tabulations, and chi-square tests to characterize and
compare the study groups. Kappa analysis to test the concordance between register
and medical record reports on pain. RESULTS: Pain was reported by 185 out of 497
children (37%; females 40%, males 35%). Level V in both Gross Motor Function
Classification System (GMFCS) and Manual Ability Classification System (MACS) was
associated with highest prevalence of pain (50% and 54%), and level I with lowest
prevalence of pain (30% and 32%). Pain was most frequent in dyskinetic CP (46%)
and least frequent in unilateral spastic CP (33%). Feet and knees were the
dominant localizations. Fair-moderate agreement (kappa 0.37, prevalence-adjusted
bias-adjusted kappa [PABAK] 0.44) was found between documented pain in CPUP and
medical records, although more seldom recognized in medical records.
INTERPRETATION: The distribution of pain between CP subtypes, functional levels,
sex, and age in CPUP is concordant with previous population-based studies,
indicating the validity of the CPUP pain screening. Despite this, further
clinical evaluation with extended pain assessments and pain management were
largely neglected in children reporting chronic pain.
PMID- 28509357
TI - Characterization of microbial mixtures by mass spectrometry.
AB - MS applications in microbiology have increased significantly in the past 10
years, due in part to the proliferation of regulator-approved commercial MALDI MS
platforms for rapid identification of clinical infections. In parallel, with the
expansion of MS technologies in the "omics" fields, novel MS-based research
efforts to characterize organismal as well as environmental microbiomes have
emerged. Successful characterization of microorganisms found in complex mixtures
of other organisms remains a major challenge for researchers and clinicians
alike. Here, we review recent MS advances toward addressing that challenge. These
include sample preparation methods and protocols, and established, for example,
MALDI, as well as newer, for example, atmospheric pressure ionization (API)
techniques. MALDI mass spectra of intact cells contain predominantly information
on the highly expressed house-keeping proteins used as biomarkers. The API
methods are applicable for small biomolecule analysis, for example, phospholipids
and lipopeptides, and facilitate species differentiation. MS hardware and
techniques, for example, tandem MS, including diverse ion source/mass analyzer
combinations are discussed. Relevant examples for microbial mixture
characterization utilizing these combinations are provided. Chemometrics and
bioinformatics methods and algorithms, including those applied to large scale MS
data acquisition in microbial metaproteomics and MS imaging of biofilms, are
highlighted. Select MS applications for polymicrobial culture analysis in
environmental and clinical microbiology are reviewed as well.
PMID- 28509358
TI - Beware of the predatory science journal: A potential threat to the integrity of
medical research.
AB - The issue of predatory journals has become increasingly more prevalent over the
past decade, as the open-access model of publishing has gained prominence.
Although the open-access model is well intentioned to increase accessibility of
biomedical research, it is vulnerable to exploitation by those looking to corrupt
medical academia and circumvent ethics and research standards. Predatory journals
will achieve publication by either soliciting unsuspecting researchers who have
legitimate research but fall victim to these predators or researchers looking to
quickly publish their research without a thorough review process. Some features
of predatory journals are a quick non-peer-review process, falsely listing or
exaggerating the credibility of editorial board members, and either lack of or
falsification of institutional affiliations and database listings. These
predatory journals are a serious threat to the integrity of medical research, as
they will infect the available literature with unsubstantiated articles, and
allow low-quality research. A number of steps can be taken to prevent the spread
and increase awareness of predatory publishers, and these must be done to
maintain the integrity of medical academia. Clin. Anat. 30:767-773, 2017. (c)
2017Wiley Periodicals, Inc.
PMID- 28509359
TI - The DNA translocase RAD5A acts independently of the other main DNA repair
pathways, and requires both its ATPase and RING domain for activity in
Arabidopsis thaliana.
AB - Multiple pathways exist to repair DNA damage induced by methylating and
crosslinking agents in Arabidopsis thaliana. The SWI2/SNF2 translocase RAD5A, the
functional homolog of budding yeast Rad5 that is required for the error-free
branch of post-replicative repair, plays a surprisingly prominent role in the
repair of both kinds of lesions in Arabidopsis. Here we show that both the ATPase
domain and the ubiquitination function of the RING domain of the Arabidopsis
protein are essential for the cellular response to different forms of DNA damage.
To define the exact role of RAD5A within the complex network of DNA repair
pathways, we crossed the rad5a mutant line with mutants of different known repair
factors of Arabidopsis. We had previously shown that RAD5A acts independently of
two main pathways of replication-associated DNA repair defined by the helicase
RECQ4A and the endonuclease MUS81. The enhanced sensitivity of all double mutants
tested in this study indicates that the repair of damaged DNA by RAD5A also
occurs independently of nucleotide excision repair (AtRAD1), single-strand break
repair (AtPARP1), as well as microhomology-mediated double-strand break repair
(AtTEB). Moreover, RAD5A can partially complement for a deficient AtATM-mediated
DNA damage response in plants, as the double mutant shows phenotypic growth
defects.
PMID- 28509360
TI - Supramolecular Assembly Mediated by Metal Ions in Aqueous Solution and Its
Application in Their Analysis.
AB - A water-soluble fluorescent sensor based on the interaction of twisted
cucurbit[14]uril (tQ[14]) and thiazole orange (TO) in aqueous solution was
developed. Formation of the tQ[14]/TO complex gives rise to stronger fluorescence
in both neutral and acidic aqueous solutions compared with that of free TO.
Further experiments on the interaction of the tQ[14]/TO complex with metal ions
revealed that, from a series of nineteen selected common metal ions, 1) only Hg2+
can lead to fluorescence enhancement and then quenching of the tQ[14]/TO (2:1)
complex in neutral aqueous solution; 2) only Ba2+ can induce fluorescence
quenching of the tQ[14]/TO (2:1) complex in aqueous HCl solution (pH 2);
furthermore, the tQ[14]/TO/Ba2+ systems exhibit reversible changes in fluorescent
intensity on successively adding SO42- and Ba2+ ; and 3) only Ba2+ or Pb2+ can
induce fluorescence quenching of the tQ[14]/TO (15:1) complex in aqueous HCl
solution (pH 2). Thus, the tQ[14]/TO complex can act as a supramolecular
fluorescence-based sensor for the determination of Hg2+ , Ba2+ , and Pb2+ ions.
PMID- 28509361
TI - Prevalence of dental developmental anomalies of permanent teeth in children and
their influence on esthetics.
AB - OBJECTIVE: The aim of this study was to determine the prevalence of dental
developmental anomalies in permanent teeth and their influence on esthetics.
MATERIALS AND METHODS: The records of 473 subjects, which comprised of
orthopantomograms, clinical examination, and anamnestic data, were explored for
dental developmental anomalies. Subjects with dental anomalies completed the
modified questionnaire. Data on reasons for seeking the treatment as well as
factors affecting the patients' satisfaction were collected. The data were
processed using the Chi-square test. RESULTS: It was found that 79 subjects
(16.7%) had at least 1 dental developmental anomaly. The most common anomalies
were hypodontia (7.2%), followed by talon cusps (3.4%), and microdontia (2.5%).
Hypodontia, microdontia, and talon cusps were found more prevalent in females
than males, whereas hyperdontia and macrodontia were more common in males. The
reason for dissatisfaction with their smile in most cases was due to missing
teeth or spacing between anterior teeth (excess space 2.9 mm +/- 1.1 mm),
followed by crowding of anterior teeth (lack of space 3.1 mm +/- 0.8mm),
difficulty maintaining oral hygiene and midline asymmetry (1.8 mm +/- 0.9 mm).
All subjects were treated using a fixed orthodontic appliance and 30 (37.9%) of
them had additional dental specialists included to achieve good esthetics and
function. Overall, 92.4% of subjects were satisfied with their resulting
appearance after treatment. CONCLUSIONS: Dental developmental anomalies are
clinically evident abnormalities. They may be the cause of various dental
problems and can influence esthetics and the development of orthodontic problems.
CLINICAL SIGNIFICANCE: This paper evaluates the distribution of dental
developmental anomalies and their influence on esthetics and function. Careful
observation and appropriate investigation are required to diagnose the condition
and institute treatment. The therapeutic approach to some dental anomalies should
be interdisciplinary.
PMID- 28509363
TI - Ni-Fe Nitride Nanoplates on Nitrogen-Doped Graphene as a Synergistic Catalyst for
Reversible Oxygen Evolution Reaction and Rechargeable Zn-Air Battery.
AB - Obtaining bifunctional electrocatalysts with high activity for the oxygen
evolution reaction (OER) and oxygen reduction reaction (ORR) is a main hurdle in
the application of rechargeable metal-air batteries. Earth-abundant 3d transition
metal-based catalysts have been developed for the OER and ORR; however, most of
these are based on oxides, whose insulating nature strongly restricts their
catalytic performance. This study describes a metallic Ni-Fe nitride/nitrogen
doped graphene hybrid in which 2D Ni-Fe nitride nanoplates are strongly coupled
with the graphene support. Electronic structure of the Ni-Fe nitride is changed
by hybridizing with the nitrogen-doped graphene. The unique heterostructure of
this hybrid catalyst results in very high OER activity with the lowest onset
overpotential (150 mV) reported, and good ORR activity comparable to that for
commercial Pt/C. The high activity and durability of this bifunctional catalyst
are also confirmed in rechargeable zinc-air batteries that are stable for 180
cycles with an overall overpotential of only 0.77 V at 10 mA-2 .
PMID- 28509362
TI - Developing Polyamine-Based Peptide Amphiphiles with Tunable Morphology and
Physicochemical Properties.
AB - The ability to tune supramolecular properties such as size, morphology, or
metabolic stability is of paramount importance in the field of supramolecular
chemistry. Peptide amphiphiles (PAs) are a family of functional self-assembling
biomaterials that have garnered widespread attention due to their broad
applicability in medicine. PAs are generally comprised of an amino acid sequence
connected to lipid tail(s) allowing them to self-assemble into supramolecular
structures with diverse morphologies. Herein, this study describes the synthesis
of a new class of polyamine-based "hybrid" PAs (PPAs) as novel self-assembling
systems. The described molecules possess diverse polyamine head groups with the
goal of tuning physicochemical properties. The findings indicate that small
changes in the polyamine head groups result in altered PPA morphologies
(nanofibers, micelles, nanoworms). The PPAs present a wide range of
physicochemical characteristics, show superior resistance to aggregation, a
diverse metabolic profile, and varied assembling kinetics. Most of the PPAs do
not show toxicity in the human cells lines evaluated. The PPAs described herein
hold promising potential as a safe and nontoxic option for drug delivery,
targeting, and tissue engineering applications.
PMID- 28509364
TI - How do caregivers understand and respond to unsettled infant behaviour in
Vietnam? A qualitative study.
AB - BACKGROUND: Unsettled infant behaviours are a common source of concern for new
parents and have been associated with perinatal common mental disorders amongst
women in high-income settings. There is little evidence about how unsettled
infant behaviours are understood and managed in low and lower-middle income
countries. This study aimed to describe caregivers' understandings of, and
responses to, unsettled infant behaviours in Vietnam and their family caregiving
contexts. METHODS: Women who were mothers of infants aged 0-6 months were
purposively recruited from two sites in Thua Thien Hue Province, Vietnam (one
urban and one rural). An additional group of women who were grandmothers were
recruited by snowball sampling. Data were collected in semi-structured interviews
about demographic information, infant feeding practices, descriptions of infant
crying episodes, beliefs about why infants cry, settling strategies, infant
sleeping arrangements and sources of advice on infant care. Translated interview
transcripts were analysed thematically. RESULTS: Twenty-four interviews were
undertaken (21 with mothers and 3 with grandmothers). Five major themes emerged
from the data after analysis: infant settling techniques, sources of information
on unsettled infant behaviour, understandings of the causes of infant crying, the
emotional responses of caregivers and the intergenerational household context.
Infants were commonly cared for by people from multiple generations, particularly
during the day. Infant settling was characterized by attending to infants
immediately, breastfeeding and bed-sharing with parents during the night. Most
mothers received advice on caregiving from family members. Infant crying was
attributed to hunger and loneliness, as well as traditional beliefs that the
infant was being upset by 'ghosts' or becoming 'hot'. Women described feeling
anxious, frustrated and helpless in relation to unsettled behaviours amongst
their infants. CONCLUSIONS: Educational interventions on interpreting infant
cues, infant sleep requirements and bed sharing may be appropriate in Vietnam if
multiple generations are included and traditional beliefs about infant crying are
addressed.
PMID- 28509365
TI - The degree of satisfaction of in-hospital medical patients with nursing care and
predictors of dissatisfaction: findings from a secondary analysis.
AB - BACKGROUND: Patient satisfaction with nursing care (NC) is an important predictor
of overall satisfaction with the hospital experience. However, the concept of
patient satisfaction has been criticised both at the theoretical and at the
methodological levels, and more attention on patient dissatisfaction has been
called for with the aim of identifying strategies to improve the quality of care.
AIMS: To describe dissatisfaction with NC as perceived by acute medical patients
and identify predictors. DESIGN AND METHODS: A secondary analysis of longitudinal
data involving 12 Italian medical units was performed. A consecutive sample of
1016 patients >=65 years (2012-2013) was included, and their satisfaction with NC
was assessed, administering the Italian version of the Patient Satisfaction Scale
(PSS) at the day of discharge. The scale was based on 11 items evaluated on a
four-point Likert scale (score ranging from 11 - very dissatisfied to 44 - very
satisfied). Patients were defined as 'satisfied with NC' when the score was >=33,
whereas they were considered as 'dissatisfied with NC' when the score was <33. A
logistic regression analysis was performed to identify the predictors of patient
dissatisfaction with NC. RESULTS: There were 788 (77.6%) patients satisfied (>=33
at the PSS) and 228 (22.4%) dissatisfied with NC (<33). The risk of
dissatisfaction was likely to be higher in female patients (RR 1.883, 95% CI
1.359-2.609), in those who developed pressure sores during the in-hospital stay
(RR 1.555, 95% CI 1.021-2.368), who received NC with high skill mix (RR 1.072,
95% CI 1.034-1.111) and those who were admitted to a large hospital (RR 1.001,
95% CI 1.001-1.002). In contrast, increased age (RR 0.987, 95% CI 0.975-0.998),
increased amount of care offered by Registered Nurses (RR 0.984, 95% CI 0.974
0.994), a higher proportion of baccalaureate nurses on staff (RR 0.975, 95% CI
0.958-0.993) and being admitted to a teaching hospital (RR 0.497, 95% CI 0.130
0.910) all decreased the likelihood of being dissatisfied with NC. CONCLUSIONS:
Dissatisfaction with NC was affected by individual, NC and hospital variables,
such as the amount of staff resources, nurses education and skill mix. The
findings emerged may inform clinicians, managers and policymakers regarding
strategies that should be designed and implemented to prevent patient
dissatisfaction.
PMID- 28509366
TI - On the quality of adjustment to retirement: The longitudinal role of personality
traits and generativity.
AB - OBJECTIVE: Although psychological factors have been explored in relation to other
life transitions, their influence on retirement adjustment quality has been
largely overlooked. This study assessed the contribution of personality traits
and generativity before retirement in the prediction of hedonic and eudaimonic
well-being at two temporal points after retirement. METHOD: This article analyzes
data from the Midlife in the United States (MIDUS) longitudinal sample.
Specifically, it uses a subsample of people who were not retired at Time 1, but
were 9 years after at Time 2 (n = 548) and 18 years after at Time 3 (n = 351).
RESULTS: After controlling both for initial values on hedonic and eudaimonic well
being and for the effects of personal attributes and resources, higher scores on
Extraversion at Time 1 significantly predicted hedonic well-being at Time 2,
whereas lower scores on Neuroticism and higher scores on generativity at Time 1
significantly predicted eudaimonic well-being at Time 2. Neuroticism and
generative concern at Time 1 remained significant in the prediction of eudaimonic
well-being at Time 3. CONCLUSIONS: The study shows that personality traits and
generative concern at midlife explain a meaningful part of the variation in
individuals' quality of subsequent retirement adjustment.
PMID- 28509368
TI - Shining the spotlight on education.
PMID- 28509367
TI - Measuring change in perceived well-being of family caregivers: validation of the
Spanish version of the Perceived Change Index (PCI-S) in Chilean dementia
caregivers.
AB - OBJECTIVE: Few instruments evaluate family caregiver perceptions of challenges
caring for persons with dementia and improvement or worsening in these areas. To
address this measurement gap, we examine psychometric properties of a Spanish
version of the 13-item Perceived Change Index (PCI-S), originally validated with
English-speaking caregivers. METHODS: Cross-sectional study with 94 caregivers of
persons with mild to moderate dementia in Chile. Interviews included caregiver
demographics, burden, health perception, distress with behaviours, dementia
severity, behavioural symptoms and functionality. RESULTS: Caregiver mean age was
55.9 (SD +/- 14.14) years and mean years caregiving was 3 (SD +/- 2.60). The
scale had strong internal consistency (Cronbach alpha = 0.94), and inter-observer
consistency (CCI = 0.99; 95% CI = 0.95-0.99). Two factors were identified:
Management skills (alpha = 0.89), and somatic well-being and affects (alpha =
0.92), explaining 63% of scale variance. Significant associations supporting
convergent validity were observed for PCI-S and subscales with caregiver burden
(p < 0.01), health perceptions (p < 0.01), depressive symptoms (p < 0.01) and
distress with behaviours (p < 0.01); and in persons with dementia, functionality
(p < 0.05), dementia severity (p < 0.05) and behavioural symptoms (p < 0.01) in
expected directions. In logistic regression models, perceived worsening (PCI-S
and subscale scores) was associated with more behavioural symptoms (OR = 1.07;
95% CI = 1.03-1.15) and caregiver burden (OR = 1.48; 95% CI = 1.18-1.86); whereas
perceived improvement was associated with higher physical functioning (OR = 0.95;
95% CI = 0.91-0.99) in persons with dementia. PCI-S scores were not associated
with socio-demographic characteristics reflecting divergent validity.
CONCLUSIONS: Spanish version of the 13-item Perceived Change Index and its two
factor solution is a valid and reliable measure with clinical utility to detect
improvement or worsening in caregivers concerning daily care challenges.
Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28509370
TI - Use of mushroom tyrosinase to introduce michaelis-menten enzyme kinetics to
biochemistry students.
AB - An inexpensive enzyme kinetics laboratory exercise for undergraduate biochemistry
students is described utilizing tyrosinase from white button mushrooms. The
exercise can be completed in one or two three-hour lab sessions. The optimal
amounts of enzyme, substrate (catechol), and inhibitor (kojic acid) are first
determined, and then kinetic data is collected in the absence and presence of the
inhibitor. A Microsoft Excel template is used to plot the data and to fit the
Michaelis-Menten equation to the data to determine the kinetic parameters Vmax
and Km . The exercise is designed to clarify and reinforce concepts covered in an
accompanying biochemistry lecture course. It has been used with positive results
in an upper-level biochemistry laboratory course for junior/senior students
majoring in chemistry or biology. (c) 2016 by The International Union of
Biochemistry and Molecular Biology, 45(3):270-276, 2017.
PMID- 28509372
TI - Differential expression of microRNA related to irritable bowel syndrome in a
rabbit model.
AB - OBJECTIVE: This study aimed to evaluate the differential expressions of microRNAs
(miRNAs) in white hair black eye (WHBE) rabbits of irritable bowel syndrome
(IBS). METHODS: WHBE and Japanese white (JW) rabbits were divided into the
control and IBS groups. The IBS groups were exposed to moist heat, stress and low
dose laxatives. Their intestinal movement rate was measured. Blood samples were
taken to detect serum 5-hydroxytryptamine (5-HT) and dopamine levels and colonic
tissues were obtained to detect c-Fos expression by immunohistochemistry. Deep
sequencing technology was used to obtain miRNA sequences in the intestinal
tissues of WHBE and JW control groups. Expressions of 14 miRNAs were measured by
real-time polymerase chain reaction in both the control and the IBS model groups.
RESULTS: Serum 5-HT and dopamine levels, intestinal movement rate and c-Fos
expressions in the WHBE rabbits were significantly increased compared with the
control group. MiR-29a-3p, miR-24-3p, miR-221-3p, let-7f-5p, let-7g-5p, let-7i
5p, miR-192-5p, miR-126-3p and miR-130b-3p expressions in WHBE IBS rabbits at day
14 were significantly higher than those in the control group while miR-324-3p and
miR-132 were downregulated. MiR-29a-3p, let-7i-5p, miR-192-5p and miR-126-3p were
significantly upregulated only in JW IBS rabbits at day 14 and miR-324-3p, miR
223-3p and miR-132 were significantly downregulated in JW IBS group. MiR-24-3p,
miR-221-3p, let-7f-5p, miR-126-3p and miR-130b-3p expressions in WHBE IBS rabbits
were higher than that in JW IBS rabbits. CONCLUSIONS: Twelve miRNAs were
differentially expressed in IBS rabbits. Five are specific in WHBE IBS rabbits,
suggesting that they play a role in increased sensitivity to IBS.
PMID- 28509371
TI - Quantitative Assessment of Sialo-Glycoproteins and N-Glycans during
Cardiomyogenic Differentiation of Human Induced Pluripotent Stem Cells.
AB - Human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC CMs) may be
used in regenerative medicine for individualized tissue transplants in the
future. For application in patients, the generated CMs have to be highly pure and
well characterized. In order to overcome the prevalent scarcity of CM-specific
markers, we quantitatively assessed cell-surface-exposed sialo-glycoproteins and
N-glycans of hiPSCs, CM progenitors, and CMs. Applying a combination of metabolic
labeling and specific sialo-glycoprotein capture, we could highly enrich and
quantify membrane proteins during cardiomyogenic differentiation. Among them we
identified a number of novel, putative biomarkers for hiPSC CMs. Analysis of the
N-glycome by capillary gel electrophoresis revealed three novel structures
comprising beta1,3-linked galactose, alpha2,6-linked sialic acid and complex
fucosylation; these were highly specific for hiPSCs. Bisecting GlcNAc structures
strongly increased during differentiation, and we propose that they are
characteristic of early, immature CMs.
PMID- 28509373
TI - BK viremia surveillance and outcomes in simultaneous pancreas-kidney transplant
recipients.
AB - BACKGROUND: While screening for asymptomatic BK viremia (BKV) has been well
studied in isolated kidney transplant recipients, there is a paucity of published
outcomes in simultaneous pancreas-kidney (SPK) transplant recipients who
underwent BKV screening followed by pre-emptive reduction in immunosuppression.
METHODS: This is a single-center, retrospective review of 31 consecutive SPK
recipients who were transplanted over a 5-year period following the initiation of
a serum BKV screening protocol. RESULTS: BK viremia developed in 11 (35.5%)
patients, and all patients achieved complete viral clearance following reduction
in immunosuppression. Two patients (6.5%) developed BK virus nephropathy, but
both had preserved allograft function. One patient developed mild rejection of
the kidney allograft following clearance of BKV, and two patients developed mild
rejection of the pancreas allograft after reduction in immunosuppression, but
there were no kidney or pancreas allograft losses due to rejection. The
development of BK viremia did not impact overall patient survival or kidney and
pancreas allograft survival. CONCLUSION: Screening asymptomatic SPK recipients
for BKV followed by reduction in maintenance immunosuppression appears to be an
effective strategy to prevent kidney allograft dysfunction and graft loss due to
BK virus nephropathy, without compromising pancreas allograft outcomes.
PMID- 28509374
TI - The STENOFOLIA gene from Medicago alters leaf width, flowering time and
chlorophyll content in transgenic wheat.
AB - Molecular genetic analyses revealed that the WUSCHEL-related homeobox (WOX) gene
superfamily regulates several programs in plant development. Many different
mechanisms are reported to underlie these alterations. The WOX family member
STENOFOLIA (STF) is involved in leaf expansion in the eudicot Medicago
truncutula. Here, we report that when this gene was ectopically expressed in a
locally adapted hard red winter wheat cultivar (Triticum aestivum), the
transgenic plants showed not only widened leaves but also accelerated flowering
and increased chlorophyll content. These desirable traits were stably inherited
in the progeny plants. STF binds to wheat genes that have the (GA)n /(CT)n DNA
cis element, regardless of sequences flanking the DNA repeats, suggesting a
mechanism for its pleiotropic effects. However, the amino acids between position
91 and 262 in the STF protein that were found to bind with the (GA)n motif have
no conserved domain with any other GAGA-binding proteins in animals or plants. We
also found that STF interacted with a variety of proteins in wheat in yeast 2
hybrid assays. We conclude that the eudicot STF gene binds to (GA)n /(CT)n DNA
elements and can be used to regulate leaf width, flowering time and chlorophyll
content in monocot wheat.
PMID- 28509375
TI - Chronic nicotine-induced changes in gene expression of delta and kappa-opioid
receptors and their endogenous ligands in the mesocorticolimbic system of the
rat.
AB - Delta and kappa opioid receptors (DOR and KOR, respectively) and their endogenous
ligands, proenkephalin (PENK) and prodynorphin (PDYN)-derived opioid peptides are
proposed as important mediators of nicotine reward. This study investigated the
regulatory effect of chronic nicotine treatment on the gene expression of DOR,
KOR, PENK and PDYN in the mesocorticolimbic system. Three groups of rats were
injected subcutaneously with nicotine at doses of 0.2, 0.4, or 0.6 mg/kg/day for
6 days. Rats were decapitated 1 hr after the last dose on day six, as this timing
coincides with increased dopamine release in the mesocorticolimbic system. mRNA
levels in the ventral tegmental area (VTA), lateral hypothalamic area (LHA),
amygdala (AMG), dorsal striatum (DST), nucleus accumbens, and medial prefrontal
cortex were measured by quantitative real-time PCR. Our results showed that
nicotine upregulated DOR mRNA in the VTA at all of the doses employed, in the AMG
at the 0.4 and 0.6 mg/kg doses, and in the DST at the 0.4 mg/kg dose. Conversely,
PDYN mRNA was reduced in the LHA with 0.6 mg/kg nicotine and in the AMG with 0.4
mg/kg nicotine. KOR mRNA was also decreased in the DST with 0.6 mg/kg nicotine.
Nicotine did not regulate PENK mRNA in any brain region studied.
PMID- 28509376
TI - Adverse Childhood Experiences (ACEs), Stress and Mental Health in College
Students.
AB - The goal of this short-term longitudinal study was to examine whether adverse
childhood experiences (ACEs) could be used to identify college students at risk
for mental health problems and whether current level of stress mediates the
relationship between ACEs and mental health. Data on ACEs and mental health
(depression, anxiety and suicidality) were collected at the beginning of the
semester, and data on current stressors and mental health were collected toward
the end of the semester (n = 239). Findings indicated that ACEs predicted
worsening of mental health over the course of a semester and suggested current
number of stressors as a mediator of the relationship between ACEs and mental
health. Results suggest that screening for ACEs might be useful to identify
students at high risk for deterioration in mental health. Results further suggest
that stress-related interventions would be beneficial for students with high
levels of ACEs and point to the need for more research and strategies to increase
help-seeking in college students.
PMID- 28509377
TI - H3.1 K36M mutation in a congenital-onset soft tissue neoplasm.
AB - We describe a patient who presented with a congenital soft tissue lesion
initially diagnosed as infantile fibromatosis at 15 days of age. Unusually, the
mass demonstrated malignant progression leading to death at 20 months of age.
Biological progression to malignancy is not known to occur in fibromatosis, and
fibrosarcoma is not known to progress from a benign lesion. Whole-exome
sequencing of the tumor identified a driver mutation in histone H3.1 at lysine
(K)36. Our findings support the link between oncohistones and infantile soft
tissue tumors and provide additional evidence for the oncogenic effects of p.K36M
in H3 variants.
PMID- 28509378
TI - Evaluation of the skin phototoxicity and photosensitivity of honeybee venom.
AB - OBJECTIVE: Bee (Apis mellifera L.) venom (BV) has been used as a cosmetic
ingredient owing to its anti-aging, anti-inflammatory, and antibacterial effects.
The aim of this study was to assess the skin safety of BV. METHODS: For this
purpose, skin phototoxicity and sensitization tests were conducted in healthy
male Hartley guinea pigs. The animals were divided into three groups (n=5) for
the phototoxicity test: G1 (negative control), G2 (BV gel treatment), and G3
(positive control). After specified treatments, the animals were irradiated with
ultraviolet A (15 J/cm2 ). The photosensitivity test was also performed in three
groups: G4 (negative control, n=5), G5 (BV gel treatment, n=10), and G6 (positive
control, n=5). RESULTS: Erythema and edema were observed after 24, 48, and 72
hours in the positive control group, but not in the negative control and BV gel
groups. Application of BV to the guinea pig skin had no toxic effects on any
clinical signs, body weight, or mortality. In addition, it did not evoke a skin
reaction in both either the skin phototoxicity and skin photosensitization tests.
CONCLUSION: Therefore, it can be concluded that BV has the potential to be
developed as a drug ingredient for topical uses.
PMID- 28509380
TI - Amyloid is essential but insufficient for Alzheimer causation: addition of
subcellular cofactors is required for dementia.
AB - OBJECTIVE: The aim of this study is to examine the hypotheses stating the
importance of amyloid or of its oligomers in the pathogenesis of Alzheimer's
disease (AD). METHODS: Published studies were examined. RESULTS: The importance
of amyloid in the pathogenesis of AD is well established, yet accepting it as the
main cause for AD is problematic, because amyloid-centric treatments have
provided no clinical benefit and about one-third of cognitively normal, older
persons have cerebral amyloid plaques. Also problematic is the alternative
hypothesis that, instead of amyloid plaques, it is oligomers of amyloid precursor
protein that cause AD.Evidence is presented suggesting amyloid/oligomers as
necessary but insufficient causes of the dementia and that, for dementia to
develop, requires the addition of cofactors known to be associated with AD. Those
cofactors include several subcellular processes: mitochondrial impairments; the
Wnt signaling system; the unfolded protein response; the ubiquitin proteasome
system; the Notch signaling system; and tau, calcium, and oxidative damage.
CONCLUSIONS: A modified amyloid/oligomer hypothesis for the pathogenesis of AD is
that activation of one or more of the aforementioned cofactors creates a burden
of functional impairments that, in conjunction with amyloid/oligomers, now
crosses a threshold of dysfunction that results in clinical dementia. Of
considerable importance, several treatments that might reverse the activation of
some of the subcellular processes are available, for example, lithium,
pioglitazone, erythropoietin, and prazosin; they should be given in combination
in a clinical trial to test their safety and efficacy. (c) 2017 John Wiley &
Sons, Ltd.
PMID- 28509379
TI - Microbial Eukaryotes that Lack Sterols.
AB - It is widely held that sterols are key cyclic triterpenoid lipids in eukaryotic
cell membranes and are synthesized through oxygen-dependent multienzyme pathways.
However, there are known exceptions-ciliated protozoans, such as Tetrahymena,
along with diverse low-oxygen-adapted eukaryotes produce, instead of sterols, the
cyclic triterpenoid lipid tetrahymanol that does not require molecular oxygen for
its biosynthesis. Here, we report that a number of anaerobic microbial eukaryotes
(protists) utilize neither sterols nor tetrahymanol in their membranes. The lack
of detectable sterol-like compounds in their membranes may provide an opportunity
to reconsider the physiological function of sterols and sterol-like lipids in
eukaryotes.
PMID- 28509381
TI - Topography-Guided Control of Local Migratory Behaviors and Protein Expression of
Cancer Cells.
AB - In vivo cancer cell migration and invasion are directed by biophysical guidance
mechanisms such as pre-existing microtracks and basement membrane extracellular
matrices. Here, this paper reports the correlation of the local migratory
behavior of cancer cells and the biochemical signal expression using the
topography that can guide or inhibit cell behaviors. To this end, the local
apparent migration and the protein expression level are investigated with respect
to the topographical feature size (flat, nanoline, and microline) and orientation
(microline, microconcentric, and microradial) with the collectively migrating
(A431) and individually migrating (MDA-MB-231 and U-87-MG) cancer cells. The
results show that the migration and the protein expression of focal adhesion
kinase, rho-associated protein kinase, and extracellular signal-regulated kinase
are localized in the periphery of cell colony. Furthermore, the inhibition of
migratory behavior at the periphery recues the protein expression, while the
guidance of migration enhances the aforementioned protein expression. The results
may imply the employ of biophysical inhibitory factors can help to control
invasiveness of cancer cells during the progression state.
PMID- 28509382
TI - Paratesticular desmoplastic small round cell tumors: A case report and review of
the literature.
AB - Desmoplastic small round cell tumor (DSCRT) is a rare malignancy most often seen
in the abdomen or pelvis of young men. Unfortunately, this disease is usually
metastatic at diagnosis and has dismal outcomes. We describe a case of isolated
paratesticular DSCRT in a 14-year-old male successfully treated with surgical
resection, chemotherapy, and adjuvant radiation, and we present a review of the
relevant literature. It appears that isolated, paratesticular DSCRTs have a
markedly better outcome than the classic abdominal or pelvic location. We
hypothesize that this is due to earlier detection and the relative ease of
surgical resection.
PMID- 28509383
TI - Arab-Levantine personality structure: A psycholexical study of modern standard
Arabic in Lebanon, Syria, Jordan, and the West Bank.
AB - OBJECTIVE: The debate of whether personality traits are universal or culture
specific has been informed by psycholexical (or lexical) studies conducted in
tens of languages and cultures. We contribute to this debate through a series of
studies in which we investigated personality descriptors in Modern Standard
Arabic, the variety of Arabic that is presumably common to about 26 countries and
native to more than 200 million people. METHOD: We identified an appropriate
source of personality descriptors, extracted them, and systematically reduced
them to 167 personality traits that are common, are not redundant with each
other, and are familiar and commonly understood in Lebanon, Syria, Jordan, and
the West Bank (Palestinian territories). RESULTS: We then analyzed self- and peer
ratings (N = 806) and identified a six-factor solution comprising Morality (I),
Conscientiousness (II), Positive Emotionality (III), Dominance (IV),
Agreeableness/Righteousness (V), and Emotional Stability (VI) without replicating
an Openness factor. CONCLUSIONS: The factors were narrower or broader variants of
factors found in the Big Five and HEXACO models. Conceptual and methodological
considerations may have impacted the factor structure.
PMID- 28509384
TI - Individual differences in personality change across the adult life span.
AB - OBJECTIVE: A precise and comprehensive description of personality continuity and
change across the life span is the bedrock upon which theories of personality
development are built. Little research has quantified the degree to which
individuals deviate from mean-level developmental trends. In this study, we
addressed this gap by examining individual differences in personality trait
change across the life span. METHOD: Data came from a nationally representative
sample of 9,636 Dutch participants who provided Big Five self-reports at five
assessment waves across 7 years. We divided our sample into 14 age groups (ages
16-84 at initial measurement) and estimated latent growth curve models to
describe individual differences in personality change across the study period for
each trait and age group. RESULTS: Across the adult life span, individual
differences in personality change were small but significant until old age. For
Openness, Conscientiousness, Extraversion, and Agreeableness, individual
differences in change were most pronounced in emerging adulthood and decreased
throughout midlife and old age. For Emotional Stability, individual differences
in change were relatively consistent across the life span. CONCLUSIONS: These
results inform theories of life span development and provide future directions
for research on the causes and conditions of personality change.
PMID- 28509385
TI - Molecular events leading to death of Leishmania donovani under spermidine
starvation after hypericin treatment.
AB - We have previously reported that the hypericin treatment caused spermidine
starvation and death of Leishmania parasite. Here, we report different molecular
events under spermidine starvation and potential role of spermidine in processes
other than redox homeostasis of the parasite. We have analyzed changes in
expression of several genes by using quantitative gene expression analysis.
Further, these changes at molecular level were also confirmed by using
biochemical and cellular studies. Altered expression of several genes involved in
redox metabolism, hypusine modification of eIF5A, DNA repair pathway and
autophagy was observed. There was decrease in Sir2RP expression after hypericin
treatment and this decrease has been found to be associated with induced ROS due
to hypericin treatment as it has been rescued by either trypanothione or
spermidine supplementation. Translation initiation in the parasite was decreased
upon spermidine starvation. We also observed increased AMPK expression upon
hypericin treatment. The increase in intracellular ATP and NAD+ levels as well as
decrease in Sir2RP expression of the parasite are cytoprotective mechanism
towards generated ROS due to hypericin treatment possibly by inducing autophagy
as indicated by increase in autophagy related gene expression and acridine orange
staining. However, the autophagy needs to be established using more rigorous
methodologies.
PMID- 28509386
TI - Descending pathways to the spinal cord in teleosts in comparison with mammals,
with special attention to rubrospinal pathways.
AB - In this article we review descending neural pathways to the spinal cord in
teleosts, compared with mammals. Descending pathways to the spinal cord are
crucial in controlling various behaviors in vertebrates. The major difference
between teleosts and mammals is the lack of corticospinal (or palliospinal)
tracts. Other descending pathways, which originate from the brain stem, are
basically identical in teleosts and mammals. This suggests the presence of common
systems in the spinal motor control by higher order centers. The homologue of
nucleus ruber remained unclear in teleosts until recently, and this review pays
special attention to the rubrospinal tract.
PMID- 28509387
TI - Progranulin increases phagocytosis by retinal pigment epithelial cells in
culture.
AB - Retinal pigment epithelium (RPE) cells take part in retinal preservation, such as
phagocytizing the shed photoreceptor outer segments (POS), every day. The
incomplete phagocytic function accelerates RPE degeneration and formation of the
toxic by-product lipofuscin. Excessive lipofuscin accumulation is characteristic
of various blinding diseases in the human eye. Progranulin is a cysteine-rich
protein that has multiple biological activities, and it has a high presence in
the retina. Progranulin has been recognized to be involved in macrophage
phagocytosis in the brain. The purpose of this study is to determine whether
progranulin influences phagocytosis by RPE cells. All experiments were performed
on primary human RPE (hRPE) cells in culture. pHrodo was used to label the
isolated porcine POS, and quantification of pHrodo fluorescence was used to
determine the degree of phagocytosis. Western blotting and immunohistochemistry
of key proteins involved in phagocytosis were used to clarify the mechanism of
progranulin. Progranulin increased RPE phagocytosis in hydrogen peroxide-treated
and nontreated RPE cells. The phosphorylated form of Mer tyrosine kinase, which
is important for POS internalization, was significantly increased in the
progranulin-exposed cells. This increase was attenuated by SU11274, an inhibitor
of hepatic growth factor receptor. Under the oxidative stress condition, exposure
to progranulin led to an approximately twofold increase in integrin alpha-v,
which is associated with the first step in recognition of POS by RPE cells. These
results suggest that progranulin could be an effective stimulator for RPE
phagocytosis and could repair RPE function. (c) 2017 Wiley Periodicals, Inc.
PMID- 28509389
TI - A Revised Sociogenomic Model of Personality Traits.
AB - In this article, I seek to update the sociogenomic model of personality traits
(Roberts & Jackson, 2008). Specifically, I seek to outline a broader and more
comprehensive theoretical perspective on personality traits than offered in the
original version of the sociogenomic model of personality traits. First, I review
the major points of our 2008 article. Second, I update our earlier model mostly
with insights derived from a deeper reading of evolutionary theoretical systems,
such as those found in life-history theory and ecological-evolutionary
developmental biology. In particular, this revision incorporates two evolutionary
informed systems, labeled pliable and elastic systems, that provide new insights
into how personality traits develop. Third, I describe some of the implications
of this new understanding of the biological and evolutionary architecture that
underlies human phenotypes such as personality traits.
PMID- 28509388
TI - Proteomic explorations of autism spectrum disorder.
AB - Proteomics, the large-scale study of protein expression in cells and tissues, is
a powerful tool to study the biology of clinical conditions and has provided
significant insights in many experimental systems. Herein, we review the basics
of proteomic methodology and discuss challenges in using proteomic approaches to
study autism. Unlike other experimental approaches, such as genomic approaches,
there have been few large-scale studies of proteins in tissues from persons with
autism. Most of the proteomic studies on autism used blood or other peripheral
tissues; few studies used brain tissue. Some studies found dysregulation of
aspects of the immune system or of aspects of lipid metabolism, but no consistent
findings were noted. Based on the challenges in using proteomics to study autism,
we discuss considerations for future studies. Apart from the complex technical
considerations implicit in any proteomic analysis, key nontechnical matters
include attention to subject and specimen inclusion/exclusion criteria, having
adequate sample size to ensure appropriate powering of the study, attention to
the state of specimens prior to proteomic analysis, and the use of a replicate
set of specimens, when possible. We conclude by discussing some potentially
productive uses of proteomics, potentially coupled with other approaches, for
future autism research including: (1) proteomic analysis of banked human brain
specimens; (2) proteomic analysis of tissues from animal models of autism; and
(3) proteomic analysis of induced pluripotent stem cells that are differentiated
into various types of brain cells and neural organoids. Autism Res 2017, 10: 1460
1469. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
PMID- 28509390
TI - Pilot study of client outcomes from exercise physiology in a youth mental health
service.
AB - The aim of this pilot study was to evaluate the utilisation and experience of an
exercise physiology programme, known as Bod Squad at a youth mental health
service. Individual sessions were offered in an outpatient setting, while both
group and individual sessions occurred in an inpatient unit. This pilot study
used a mixed methodology to collect data from young people who attended Bod
Squad. A database of exercise physiology records for 47 young people were
analysed for attendance and physiological indicators. In addition, 7 semi
structured interviews were conducted with young people to explore their
experience of Bod Squad. Young people attended a total of 169 sessions during the
programmes tenure, with an overall mean of 3.6 sessions. Pre-post measures for 10
young people (who had attended at least 4 sessions) showed modest average
reductions for body mass index, waist circumference, chest circumference and
resting heart rate. Five themes emerged from the interviews-(1) My reasons for
attending, (2) The social aspect, (3) An individualized approach, (4) Outcomes
from Bod Squad and (5) My experience of the service. All of these themes included
positive experiences of Bod Squad, which young people perceived as relevant to
their needs and helpful to their recovery. These findings are congruent with
previous studies that have concluded that exercise physiology may be an
effective, acceptable and valued intervention for addressing physical and
metabolic health issues for young people.
PMID- 28509391
TI - Common mental disorder including psychotic experiences: Trailblazing a new
recovery pathway within the Improving Access to Psychological Therapies programme
in England.
AB - Psychotic experiences, depressive and anxiety symptoms may be manifestations of a
latent continuum of common mental distress. The Improving Access to Psychological
Therapies (IAPT) programme has increased the reach of psychological treatments to
people with common mental disorders in England. However, psychotic experiences
are neither measured nor considered in therapy. We aimed to confirm the presence
of psychotic experiences among IAPT service-users and determine whether these
experiences are associated with higher depression/anxiety levels and poorer
recovery. All service-users that attended the Fenland and Peterborough IAPT teams
in Cambridgeshire between November 16, 2015 and January 29, 2016 participated in
a service evaluation. In addition to routine mesures, such as the Generalized
Anxiety Disorder-7 questionnaire (GAD-7) and the Patient Health Questionnaire-9
(PHQ-9), we introduced a shortened version of the Community Assessment of Psychic
Experiences (CAPE-P15) to measure psychotic experiences. Classes of individuals
were identified with latent class analysis. Associations were reported using
Pearson correlation coefficient. One hundred and seventy-three services-users
were included, mostly females (N = 133; 76.9%). The mean age was 36.6 (SD =
13.3). Around 30% likely belonged to a class with psychotic experiences. CAPE-P15
frequency was significantly correlated to PHQ-9 (r = 0.44; P < .001) and GAD-7 (r
= 0.32; P < .001). Similarly, CAPE-P15 distress and both PHQ-9 (r = 0.43; P <
.001) and GAD-7 (r = 0.38; P < .001) were highly correlated. These associations
were replicated after the initial period of the therapy, indicating poor
recovery. Some IAPT service-users suffer psychotic experiences. Tailoring
available evidence-based psychological therapies for these people in IAPT
settings might trailblaze a new care pathway to improve recovery in this group.
PMID- 28509393
TI - NmeA, a novel efflux transporter specific for nucleobases and nucleosides,
contributes to metal resistance in Aspergillus nidulans.
AB - Through Minos transposon mutagenesis we obtained A. nidulans mutants resistant to
5-fluorouracil due to insertions into the upstream region of the uncharacterized
gene nmeA, encoding a Major Facilitator Superfamily (MFS) transporter. Minos
transpositions increased nmeA transcription, which is otherwise extremely low
under all conditions tested. To dissect the function of NmeA we used strains
overexpressing or genetically lacking the nmeA gene. Strains overexpressing NmeA
are resistant to toxic purine analogues, but also, to cadmium, zinc and borate,
whereas an isogenic nmeADelta null mutant exhibits increased sensitivity to these
compounds. We provide direct evidence that nmeA overexpression leads to efflux of
adenine, xanthine, uric acid and allantoin, the latter two being intermediate
metabolites of purine catabolism that are toxic when accumulated cytoplasmically
due to relevant genetic lesions. By using a functional GFP-tagged version we show
that NmeA is a plasma membrane transporter. Homology modeling and docking
approaches identified a single purine binding site and a tentative substrate
translocation trajectory in NmeA. Orthologues of NmeA are present in all
Aspergilli and other Eurotiomycetes, but are absent from other fungi or non
fungal organisms. NmeA is thus the founding member of a new class of transporters
essential for fungal success under specific toxic conditions.
PMID- 28509394
TI - Room-Temperature Oligomeric Discotic Nematic Liquid Crystals over a Wide
Temperature Range: Structure-Property Relationships.
AB - The design and synthesis of three room-temperature discotic nematic (ND ) liquid
crystals (LCs) is presented. The LC consists of an azobenzene core attached to
which are four pentaalkynylbenzene (PA) units through flexible alkyl spacers. The
presence of a short azo linking group provides more disorder in the system,
thereby reducing the packing efficiency among the PA units and resulting into the
formation of a room-temperature ND phase over a wide temperature range.
Dielectric constant and birefringence studies were performed to gain further
insights into the physical properties of the mesophase.
PMID- 28509392
TI - Aflatoxin B1 exposure increases the risk of cirrhosis and hepatocellular
carcinoma in chronic hepatitis B virus carriers.
AB - The relation between aflatoxin B1 (AFB1 ) and cirrhosis in chronic carriers of
hepatitis B virus (HBV) remains inconclusive. This case-control study nested in a
large community-based cohort aimed to assess the effect of AFB1 exposure on
cirrhosis and HCC in chronic HBV carriers. Serum AFB1 -albumin adduct levels at
study entry were measured in 232 cirrhosis cases, 262 HCC cases and 577 controls.
Multivariate-adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs)
were estimated using logistic regression. Among all chronic HBV carriers, the
time intervals between study entry and diagnosis of HCC, cirrhosis, cirrhotic
HCC, and non-cirrhotic HCC were all significantly (p < 0.0001) shorter in
participants with high serum levels of AFB1 -albumin adducts than those with
low/undetectable levels. There were significant dose-response relations with
serum AFB1 -albumin adduct level at study entry for cirrhosis (p-trend = 0.0001)
and cirrhotic HCC (p-trend < 0.0001) newly diagnosed within 9 years after entry
as well as non-cirrhotic HCC (p-trend = 0.021) newly diagnosed within 4 years
after entry. The aORs (95% CIs) for high versus undetectable serum AFB1 -albumin
adduct levels were 2.45 (1.51-3.98) for cirrhosis (p = 0.0003), 5.47 (2.20-13.63)
for cirrhotic HCC (p = 0.0003), and 5.39 (1.11-26.18) for non-cirrhotic (p =
0.0368) HCC, respectively. There remained a significant dose-response relation
between serum AFB1 -albumin adduct level and HCC risk (p-trend = 0.0291) in
cirrhosis patients, showing an aOR (95% CI) of 3.04 (1.11-8.30) for high versus
undetectable serum levels (p = 0.0299). It is concluded that AFB1 exposure may
increase the risk of cirrhosis and HCC in a dose-response manner among chronic
HBV carriers.
PMID- 28509395
TI - DA-EPOCH-R for post-transplant lymphoproliferative disorders.
AB - BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are a
potentially fatal group of neoplasms arising in an immunodeficient environment.
Although the cornerstone of treatment is reduced immunosuppression (RI), advanced
cases often warrant treatment with chemoimmunotherapy. The chemoimmunotherapy
regimen of dose-adjusted (DA)-EPOCH-R is superior to R-CHOP in HIV associated
aggressive lymphomas, suggesting that it might also be favorable in the setting
of PTLD. METHODS: We performed a retrospective analysis of patients with advanced
monomorphic PTLD treated with first line DA-EPOCH-R in addition to RI at our
institution from 2003-2016. RESULTS: Seven patients were included. Mean age was
51 and mean time from transplant to diagnosis was 71 months. Six of the seven
patients received a kidney transplant, six had stage III or IV disease, six had
tumors that were EBV positive, and six completed therapy. All six patients who
completed therapy achieved a complete response. Mean PFS and OS were 46.6 and
52.6 months, respectively. Treatment was well-tolerated with no significant
treatment related morbidity or mortality. CONCLUSIONS: Our findings support
several observations in the literature that DA-EPOCH-R is efficacious and well
tolerated for the treatment of advanced, monomorphic PTLD.
PMID- 28509396
TI - Anti-inflammatory, antioxidant, and immunomodulatory effects of curcumin in
ovalbumin-sensitized rat.
AB - BACKGROUND: Anti-inflammatory and antioxidant properties of curcumin have been
shown. In this study, anti-inflammatory, antioxidant, and immunomodulatory
effects of curcumin in sensitized rat were evaluated. METHODS: Six groups of rats
including control (C), ovalbumin-sensitized (as a rat model of asthma, S), S
groups treated with curcumin (Cu 0.15, 0.30, and 0.60 mg/mL), and 1.25 MUg/mL
dexamethasone (S + D) were studied. Curcumin and dexamethasone were given in
animals' drinking water during sensitization period. Total and differential WBC
count, PLA2, TP, IFN-gamma, IL-4, IgE, oxidant, and antioxidant biomarker levels
in bronchoalveolar lavage fluid (BALF) were examined. RESULTS: Total WBC,
neutrophil and eosinophil counts, levels of PLA2, TP, IgE, IL-4, NO2 , NO3 , and
MDA in BALF were increased but lymphocyte percentage, SOD, CAT, thiol, and IFN
gamma levels and IFN-gamma/IL-4 ratio decreased in S animals compared to controls
(P < 0.001 for all cases). Treatment with all concentrations of curcumin
significantly improved total WBC, PLA2, TP, IgE, IL-4, IFN-gamma, IFN-gamma/IL-4
ratio, SOD, thiol, NO2 , and NO3 compared to S group (P < 0.01 to P < 0.001). Two
higher concentrations of curcumin significantly decreased neutrophil and
eosinophil counts and MDA level but increased IFN-gamma, CAT and lymphocyte
values compared to S group (P < 0.001 for all cases). Dexamethasone treatment
also significantly improved most of the measured parameters (P < 0.05 to P <
0.001) but it did not change IL-4 and IFN-gamma levels and IFN-gamma/IL-4 ratio.
CONCLUSION: Anti-inflammatory, antioxidant, and immunomodulatory effects of
curcumin with more specific immunomodulatory effect on Th1/Th2 balance compared
to dexamethasone in sensitized rats was shown. (c) 2017 BioFactors, 43(4):567
576, 2017.
PMID- 28509397
TI - Sex differences in metabolic risk indicator of dementia in an elderly urban
Korean population: A community-based cross-sectional study.
AB - AIM: The aim of the present study was to evaluate the age-specific prevalence of
dementia, and develop a metabolic risk indicator for dementia according to sex.
METHODS: This cross-sectional study was carried out from September 2007 through
December 2012 with 19 935 elderly participants in metropolitan Seoul, Korea.
Multiphase assessments were used to measure metabolic risk factors and confirm
dementia according to sex. Specifically, multivariate logistic regression
analyses were used to identify how elderly men and women differed in regard to
metabolic risk indicators of dementia. RESULTS: The adjusted prevalence rates of
dementia in elderly Seoul residents were estimated at 4.9%, 6.1% and 5.6% in men,
women and the overall population, respectively. Stroke conferred an odds ratio of
5.14 (95% CI 3.91-6.77) and 2.55 (95% CI 2.01-3.25) in men and women,
respectively. Additionally, within the female population, diabetes mellitus
conferred an odds ratio of 1.29 (95% CI 1.09-1.53), whereas alcohol consumption
conferred an odds ratio of 0.77 (95% CI 0.61-0.97). CONCLUSIONS: Stroke played a
primary role as a metabolic risk indicator of dementia in elderly men, while
diabetes mellitus and alcohol abstinence were important metabolic risk factors in
elderly women. Taken together, the data show that when designing preventative
measures against dementia based on metabolic risk, sex needs to be taken into
account. Geriatr Gerontol Int 2017; 17: 2136-2142.
PMID- 28509399
TI - Association of renin angiotensin antagonists with adverse perioperative events in
patients undergoing elective orthopaedic surgery: a case-control study.
AB - BACKGROUND: Renin angiotensin antagonists (RAA) may block protective vasopressor
responses during surgery. Evidence linking RAA with intraoperative hypotension
and perioperative adverse events is conflicting. AIM: To compare the incidence of
intraoperative hypotension and adverse events between patients receiving or not
receiving RAA. METHODS: This is a retrospective case-control study of 258
consecutive patients who underwent elective total knee or hip replacement between
1 January 2013 and 31 August 2016 and who were chronically prescribed a single
blood pressure-lowering agent up to the time of surgery. Primary outcome measures
were differences between patients receiving RAA (cases; n = 129) and patients
receiving non-RAA medications (controls; n = 129) in incidence of intraoperative
hypotension (systolic blood pressure <90 mmHg), perioperative acute kidney injury
(AKI, >30% increase in serum creatinine from baseline on Day 1 post-operatively)
and new onset major adverse cardiac or cerebrovascular events (MACCE) or in
hospital death over 72 h post-operatively. RESULTS: Patients receiving RAA had
significantly higher preoperative systolic blood pressure, greater prevalence of
hypertension and chronic kidney disease, lower prevalence of ischaemic heart
disease and lower cardiac risk compared to controls. Age, gender, type of
operation, operative fitness, mode and duration of anaesthesia and prevalence of
other types of cardiovascular disease, dyslipidaemia and diabetes were similar
between groups. Compared to controls, patients receiving RAA had higher incidence
of intraoperative hypotension (76.0 vs 45.9%, P < 0.001), AKI (11.6 vs 1.6%, P =
0.002) and MACCE (6.2 vs 0%, P = 0.007), with all adverse events associated with
intraoperative hypotension. CONCLUSION: This study provides further observational
evidence of RAA-induced harm in patients undergoing elective surgery, although
determining benefits and harms of preoperative withdrawal of RRA requires
prospective randomised trials.
PMID- 28509398
TI - The multicomponent antirestriction system of phage P1 is linked to capsid
morphogenesis.
AB - Bacterial Type I restriction-modification (R-M) systems present a major barrier
to foreign DNA entering the bacterial cell. The temperate phage P1 packages
several proteins into the virion that protect the phage DNA from host
restriction. Isogenic P1 deletion mutants were used to reconstitute the
previously described restriction phenotypes associated with darA and darB. While
P1DeltadarA and P1DeltadarB produced the expected phenotypes, deletions of
adjacent genes hdf and ddrA also produced darA-like phenotypes and deletion of
ulx produced a darB-like phenotype, implicating several new proteins of
previously unknown function in the P1 dar antirestriction system. Interestingly,
disruption of ddrB decreased P1's sensitivity to EcoB and EcoK restriction.
Proteomic analysis of purified virions suggests that packaging of antirestriction
components into P1 virions follows a distinct pathway that begins with the
incorporation of DarA and Hdf and concludes with DarB and Ulx. Electron
microscopy analysis showed that hdf and darA mutants also produce abnormally high
proportions of virions with aberrant small heads, which suggests Hdf and DarA
play a role in capsid morphogenesis. The P1 antirestriction system is more
complex than previously realized and is comprised of multiple proteins including
DdrA, DdrB, Hdf, and Ulx in addition to DarA and DarB.
PMID- 28509400
TI - Glycyrrhetinic Acid Accelerates the Clearance of Triptolide through P-gp In
Vitro.
AB - Triptolide (TP) is an active ingredient isolated from Tripterygium wilfordii
Hook. f. (TWHF), which is a traditional herbal medicine widely used for the
treatment of rheumatoid arthritis and autoimmune disease in the clinic. However,
its adverse reactions of hepatotoxicity and nephrotoxicity have been frequently
reported which limited its clinical application. The aim of this study was to
investigate the mechanism of glycyrrhetinic acid (GA) effecting on the
elimination of TP in HK-2 cells and the role of the efflux transporters of P-gp
and multidrug resistance-associated proteins (MRPs) in this process. An ultra
performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC
ESI-MS) analytical method was established to determine the intracellular
concentration of TP. In order to study the role of efflux transporters of P-gp
and MRPs in GA impacting on the accumulation of TP, the inhibitors of efflux
transporters (P-gp: verapamil; MRPs: MK571) were used in this study. The results
showed that GA could enhance the elimination of TP and reduce the TP accumulation
in HK-2 cells. Verapamil and MK571 could increase the intracellular concentration
of TP; in addition, GA co-incubation with verapamil significantly increased the
TP cellular concentration compared with the control group. In conclusion, GA
could reduce the accumulation of TP in HK-2 cells, which was related to P-gp.
This is probably one of the mechanisms that TP combined with GA to detoxify its
toxicity. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28509401
TI - Transitions between marine and freshwater environments provide new clues about
the origins of multicellular plants and algae.
AB - Marine-freshwater and freshwater-marine transitions have been key events in the
evolution of life, and most major groups of organisms have independently
undergone such events at least once in their history. Here, we first compile an
inventory of bidirectional freshwater and marine transitions in multicellular
photosynthetic eukaryotes. While green and red algae have mastered multiple
transitions in both directions, brown algae have colonized freshwater on a
maximum of six known occasions, and angiosperms have made the transition to
marine environments only two or three times. Next, we review the early
evolutionary events leading to the colonization of current habitats. It is
commonly assumed that the conquest of land proceeded in a sequence from marine to
freshwater habitats. However, recent evidence suggests that early photosynthetic
eukaryotes may have arisen in subaerial or freshwater environments and only later
colonized marine environments as hypersaline oceans were diluted to the
contemporary level. Although this hypothesis remains speculative, it is important
to keep these alternative scenarios in mind when interpreting the current habitat
distribution of plants and algae. Finally, we discuss the roles of structural and
functional adaptations of the cell wall, reactive oxygen species scavengers,
osmoregulation, and reproduction. These are central for acclimatization to
freshwater or to marine environments. We observe that successful transitions
appear to have occurred more frequently in morphologically simple forms and
conclude that, in addition to physiological studies of euryhaline species,
comparative studies of closely related species fully adapted to one or the other
environment are necessary to better understand the adaptive processes.
PMID- 28509402
TI - A combined hands-on teaching programme and clinical pathway focused on pleural
ultrasound and procedure supervision transforms pleural procedure outcomes.
AB - BACKGROUND: Management of pleural effusions is a common diagnostic and management
problem. AIMS: We reviewed the outcomes from pleural procedures after the
instigation of pleural effusion management guidelines, focusing on pleural
ultrasound and a hands-on teaching programme followed by procedure supervision
that enabled many operators to perform such procedures. METHODS: This is a
retrospective analysis of all procedures performed for pleural effusions on
medical patients. Outcomes were assessed prior to the instigation of pleural
effusion management guidelines (pleural pathway) and hands-on teaching (January
2010 to June 2011) and following these interventions (January 2012 to June 2013).
RESULTS: A total of 171 procedures involving 129 patients (pre-pathway group) and
146 procedures involving 115 patients (post-pathway group) was analysed. The rate
of complications prior to the pleural pathway was 22.2% (38 of 171 procedures).
Following the pathway, the rate of complications declined to 7.5% (11 of 146
procedures, P < 0.003). The use of pleural ultrasound increased dramatically
(72.5 vs 90.2%). The number of patients who underwent repeated procedures
(defined as >=3) reduced dramatically (21 vs 7, P < 0.01). This improvement
occurred using many supervised operators who completed the hands-on teaching
programme (n = 32) and followed the pleural pathway (127 of 146 procedures).
CONCLUSION: The instigation of a clinical pathway focused on the use of bedside
pleural ultrasound, and teaching of drainage techniques with procedure
supervision vastly improved patient outcomes. This not only allowed better
quality of care for patients, it also provided the acquisition of new skills to
medical staff, not limiting these skills to specialised staff.
PMID- 28509403
TI - The zebrafish embryo as a model to quantify early inflammatory cell responses to
biomaterials.
AB - To rapidly assess early inflammatory cell responses provoked by biomaterials in
the full complexity of the living organism, we developed a zebrafish embryo model
which allows real time analysis of these responses to biomaterial microspheres.
Fluorescently labeled microspheres with different properties were injected into
embryos of selected transgenic zebrafish lines expressing distinct fluorescent
proteins in their neutrophils and macrophages. Recruitment of leukocytes and
their interactions with microspheres were monitored using fluorescence
microscopy. We developed a novel method using ImageJ and the plugin ObjectJ
project file "Zebrafish-Immunotest" for rapid and semi-automated fluorescence
quantification of the cellular responses. In the embryo model we observed an
ordered inflammatory cell response to polystyrene and poly (epsilon-caprolactone)
microspheres, similar to that described for mammalian animal models. The
responses were characterized by an early infiltration of neutrophils followed by
macrophages, and subsequent differentially timed migration of these cells away
from the microspheres. The size of microspheres (10 and 15 um) did not influence
the cellular responses. Poly (epsilon-caprolactone) microspheres provoked a
stronger infiltration of neutrophils and macrophages than polystyrene
microspheres did. Our study shows the potential usefulness of zebrafish embryos
for in vivo evaluation of biomaterial-associated inflammatory cell responses. (c)
2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2522-2532, 2017.
PMID- 28509404
TI - Family therapy for autism spectrum disorders.
AB - BACKGROUND: Autism spectrum disorders (ASDs) are characterised by impairments in
communication and reciprocal social interaction. These impairments can impact on
relationships with family members, augment stress and frustration, and contribute
to behaviours that can be described as challenging. Family members of individuals
with ASD can experience high rates of carer stress and burden, and poor parental
efficacy. While there is evidence to suggest that individuals with ASD and family
members derive benefit from psychological interventions designed to reduce stress
and mental health morbidity, and enhance coping, most studies to date have
targeted the needs of either individuals with ASD, or family members. We wanted
to examine whether family (systemic) therapy, aimed at enhancing communication,
relationships or coping, is effective for individuals with ASD and their wider
family network. OBJECTIVES: To evaluate the clinical effectiveness and
acceptability of family therapy as a treatment to enhance communication or coping
for individuals with ASD and their family members. If possible, we will also seek
to establish the economic costs associated with family therapy for this clinical
population. SEARCH METHODS: On 16 January 2017 we searched CENTRAL, MEDLINE,
Embase, 10 other databases and three trials registers. We also handsearched
reference lists of existing systematic reviews and contacted study authors in the
field. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs
investigating the effectiveness of family therapy for young people or adults with
ASD or family members, or both, delivered via any modality and for an unspecified
duration, compared with either standard care, a wait-list control, or an active
intervention such as an alternative type of psychological therapy. DATA
COLLECTION AND ANALYSIS: Two authors independently screened each title and
abstract and all full-text reports retrieved. To enhance rigour, 25% of these
were independently screened by a third author. MAIN RESULTS: The search yielded
4809 records. Of these, we retrieved 37 full-text reports for further scrutiny,
which we subsequently excluded as they did not meet the review inclusion
criteria, and identified one study awaiting classification. AUTHORS' CONCLUSIONS:
Few studies have examined the effectiveness of family therapy for ASD, and none
of these are RCTs. Further research studies employing methodologically robust
trial designs are needed to establish whether family therapy interventions are
clinically beneficial for enhancing communication, strengthening relationships,
augmenting coping and reducing mental health morbidity for individuals with ASD
and family members.
PMID- 28509405
TI - Opportunities for expanding clinical trial enrollment for relapsed and refractory
pediatric acute myeloid leukemia in the United States and Canada.
PMID- 28509406
TI - High heparin content surface-modified polyurethane discs promote rapid and stable
angiogenesis in full thickness skin defects through VEGF immobilization.
AB - Three-dimensional scaffolds have the capacity to serve as an architectural
framework to guide and promote tissue regeneration. Parameters such as the type
of material, growth factors, and pore dimensions are therefore critical in the
scaffold's success. In this study, heparin has been covalently bound to the
surface of macroporous polyurethane (PU) discs via two different loading methods
to determine if the amount of heparin content had an influence on the therapeutic
affinity loading and release of (VEGF165 ) in full thickness skin defects. PU
discs (5.4 mm diameter, 300 um thickness, and interconnected pore size of 150 um)
were produced with either a low (2.5 mg/g) or high (6.6 mg/g) heparin content (LC
and HC respectively), and were implanted into the modified dorsal skin chamber
(MDSC) of C57BL/6 J mice with and without VEGF. Both low- and high-content discs
with immobilized VEGF165 (LCV and HCV, respectively) presented accelerated
neovascularization and tissue repair in comparison to heparin discs alone.
However, the highest angiogenetic peak was on day 7 with subsequent stabilization
for HCV, whereas other groups displayed a delayed peak on day 14. We therefore
attribute the superior performance of HCV due to its ability to hold more
VEGF165, based on its increased heparin surface coverage, as also demonstrated in
VEGF elution dynamics. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part
A: 105A: 2543-2550, 2017.
PMID- 28509407
TI - IL-1beta inhibits osteogenesis of human bone marrow-derived mesenchymal stem
cells by activating FoxD3/microRNA-496 to repress wnt signaling.
AB - IL-1beta, a major cytokine of proinflammatory response, has been implicated in
bone loss. However, its effects on mesenchymal progenitor cells-associated bone
regeneration remain elusive. Here, we investigated the role of microRNA for the
regulation of osteogenesis by IL-1beta in human bone marrow-derived mesenchymal
stem cells (hBMMSC). Our data suggested Homo sapiens (hsa)-miR-496 is induced by
IL-1beta in hBMMSC and mediates the decreased beta-catenin expression. Reporter
assays using the 3'-UTR of beta-catenin demonstrated sequence-dependent gene
suppression with hsa-miR-496. IL-1beta activated hsa-miR-496 expression through a
transcription factor, Foxhead box D3 protein (FoxD3). The activation of hsa-miR
496 promoter in hBMMSC depended on a consensus FoxD3 binding motif. Under
osteogenic differentiation, IL-1beta treatment or overexpressing hsa-miR-496
attenuated bone mineralization and bone marker gene expressions in hBMMSC.
Further, anti-miR-496 rescued the inhibitory effects of IL-1beta. Our findings
suggest a pivotal role of hsa-miR-496 in linking inflammation to impaired bone
regeneration, and provide a rationale for using appropriate hsa-miR-496
inhibitors in the treatment of inflammation-associated bone loss.
PMID- 28509409
TI - Soft tissue reconstruction and salvage of infected fixation hardware in lower
extremity trauma.
AB - BACKGROUND: Tibial fracture management may be complicated by infection of
internal fixation hardware (iIFH) resulting in increased morbidity and amputation
rate. When iIFH removal is not possible, salvage of the lower extremity is
attempted through debridement, antibiotics, and vascularized soft tissue
coverage. This study investigates lower extremity salvage with retention of iIFH.
METHODS: Demographics, outcomes, and bacterial speciation in patients with tibial
fractures at a level 1 trauma center from 2007 to 2014 were reviewed. The primary
outcome was infection suppression, while secondary outcomes included limb
salvage, amputation, and osseous union. RESULTS: Twenty-five patients underwent
soft tissue reconstruction for salvage of iIFH. Average age was 41, 19 (76%) were
male, average BMI 30.1 kg/m2 , 10 (40%) patients smoked. Tibial fractures were
closed in 8 (32%), Gustilo-Anderson grade I in 1 (4%), II in 8 (32%), IIIb in 5
(20%), and IIIc in 1 (4%). Staphylococcus was most commonly cultured with 11
(44%) demonstrating methicillin-resistance. Soft tissue reconstruction was
performed by local flap in 15 (60%) and free flap in 10 (40%). At an average of
16.1 months, 19 (76%) hardware salvage patients demonstrated clinical suppression
of infection, 11 of 19 (57.9%) patients had bony union, and 24 (96%) maintained a
salvaged limb. One patient was amputated for recurrent infection. CONCLUSIONS:
Following complex, infected tibial fractures, salvage of the lower extremity may
be attempted even when iIFH cannot be removed. Thorough debridement, antibiotics,
and vascularized soft tissue may suppress infection long enough to facilitate
osseous union and subsequent removal of iIFH.
PMID- 28509408
TI - Insulin-associated weight gain in obese type 2 diabetes mellitus patients: What
can be done?
AB - Insulin therapy (IT) is initiated for patients with type 2 diabetes mellitus when
glycaemic targets are not met with diet and other hypoglycaemic agents. The
initiation of IT improves glycaemic control and reduces the risk of microvascular
complications. There is, however, an associated weight gain following IT, which
may adversely affect diabetic and cardiovascular morbidity and mortality. A 3 to
9 kg insulin-associated weight gain (IAWG) is reported to occur in the first year
of initiating IT, predominantly caused by adipose tissue. The potential causes
for this weight gain include an increase in energy intake linked to a fear of
hypoglycaemia, a reduction in glycosuria, catch-up weight, and central effects on
weight and appetite regulation. Patients with type 2 diabetes who are receiving
IT often have multiple co-morbidities, including obesity, that are exacerbated by
weight gain, making the management of their diabetes and obesity challenging.
There are several treatment strategies for patients with type 2 diabetes, who
require IT, that attenuate weight gain, help improve glycaemic control, and help
promote body weight homeostasis. This review addresses the effects of insulin
initiation and intensification on IAWG, and explores its potential underlying
mechanisms, the predictors for this weight gain, and the available treatment
options for managing and limiting weight gain.
PMID- 28509410
TI - Anti-inflammatory, anti-osteoclastic, and antioxidant activities of genistein
protect against alveolar bone loss and periodontal tissue degradation in a mouse
model of periodontitis.
AB - Genistein, a dietary polyphenol primarily found in soy products, has beneficial
effects on bone. However, the effect of genistein on inflammatory periodontal
destruction has not been investigated in detail. We explored whether genistein
protects against lipopolysaccharide (LPS)/ligature-induced periodontitis in mice.
We also examined the effect of genistein on LPS-stimulated inflammatory and
oxidative stress using RAW 264.7 macrophages and human gingival fibroblasts
(hGFs). The results from MUCT and histological analyses revealed that
intraperitoneal injection of genistein (20 mg/kg body weight) daily for three
weeks inhibited LPS-mediated alveolar bone loss and periodontal tissue
degradation. The administration of genistein also inhibited osteoclast formation
and the expression of inflammation-related molecules in the inflamed region of
mice with periodontitis. Treatment with 30-70 MUM genistein significantly
prevented osteoclast differentiation in receptor activator of nuclear factor
kappaB ligand- or LPS-stimulated macrophages by suppressing the expression of
osteoclast-specific molecules. The addition of genistein led to a dose-dependent
inhibition of the expression of inflammation-related molecules both in LPS
stimulated macrophages and hGFs. In addition, genistein at 50 MUM protected hGFs
from LPS-mediated stresses such as mitochondrial impairment and cellular ROS
accumulation. However, such protection was significantly diminished by combined
treatment with 25 nM bafilomycin A1, a chemical autophagy inhibitor.
Collectively, our results indicate that genistein protects against inflammatory
periodontal damage by regulating autophagy induction and inhibiting osteoclast
activation, the production of inflammation mediators, and mitochondrial oxidative
damage. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2510
2521, 2017.
PMID- 28509411
TI - Variations in Duchenne muscular dystrophy course in a multi-ethnic UK population:
potential influence of socio-economic factors.
AB - AIM: To explore variation in clinical course and steroid treatment in Duchenne
muscular dystrophy (DMD) by ethnic origin and socio-economic status. METHOD: In
this longitudinal cohort study, clinical outcome was defined as age at loss of
ambulation (LOA). Ages are presented as months for accurate calculation. Steroid
use was reviewed against national guidelines. Kaplan-Meier survival analysis was
used to determine probabilities over time of LOA. Log-rank test was used to
evaluate comparisons between ethnic and socio-economic groups. RESULTS: From 2005
to 2014, 71 children were newly diagnosed with DMD. Complete data were available
on 69, including 33 of white British heritage and 23 of South Asian heritage.
Mean age at diagnosis (without known family history) was 45.7 months; white
British ethnicity 42.1 months (range 14-86mo), South Asian ethnicity 50.2 months
(range 5-98mo). Twenty-four males lost ambulation. Those of South Asian heritage
lost ambulation earlier (mean LOA 105.8mo [8y 10mo]) than those of white British
heritage (mean LOA 117.8mo [9y 10mo]): log-rank test score 0.012 (p<0.05). Those
most deprived did worse: mean age at LOA 130.0 months (10y 10mo) for the top 20
per cent and 102.5 months (8y 6mo) in the lower 20 per cent: log-rank test score
0.035 (p<0.05). The most socially deprived were diagnosed earlier and started
steroids earlier. Of those of South Asian heritage, 18 per cent declined
steroids, compared with 9 per cent of white British heritage. Also, 44 per cent
of those of South Asian heritage stopped steroids compared with 17 per cent of
those of white British heritage. INTERPRETATION: Patients from South Asian and
deprived backgrounds had earlier LOA. Genetic disease modifiers are likely to be
implicated, but social and cultural factors influence access to treatment.
PMID- 28509412
TI - "Three Hits" Hypothesis for Developmental Origins of Health and Diseases in View
of Cardiovascular Abnormalities.
AB - "Fetal Origins of Adult Diseases" (FOAD) or "Barker hypothesis," also known as
the developmental origins of health and diseases (DoHaD), was initially proposed
by David Barker in the 1980s. Progress in past 2 to 3 decades demonstrated that
many adult disorders, including hypertension, diabetes, obesity, cancer, and
others, could be linked to poor development resulting from in utero insults.
Utero-environments play a critical role in fetal development. Because the
placenta and umbilical cord are the only important connections between the fetus
and mother in the uterus, this review pays special attention to recent research
and progress in the study of the relationship between those tissues and FOAD. We
discuss the conception and possible underlying mechanisms of FOAD, and focus on
cardiovascular diseases and epigenetic mechanisms. This review also summarizes
physiology, pathology, and the important roles of fetoplacental vasculature,
which might contribute to FOAD as initiators. We proposed the "Three hits"
hypothesis that highlights the importance of intrauterine and early postnatal
factors as contributors to FOAD, which could be significant for early prevention
and treatments of FOAD. Birth Defects Research 109:744-757, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28509413
TI - Microcarriers with Synthetic Hydrogel Surfaces for Stem Cell Expansion.
AB - Microcarriers are scalable support surfaces for cell growth that enable high
levels of expansion, and are particularly relevant for expansion of human
mesenchymal stem cells (hMSCs). The goal of this study is to develop a
poly(ethylene glycol) (PEG)-based microcarrier coating for hMSC expansion.
Commercially available microcarriers do not offer customizability of microcarrier
surface properties, including elastic modulus and surface cell adhesion ligands.
The lab has previously demonstrated that tuning these material properties on PEG
based hydrogels can modulate important cellular growth characteristics, such as
cell attachment and expansion, which are important in microcarrier-based culture.
Eosin-Y is adsorbed to polystyrene microcarriers and used as a photoinitiator for
thiol-ene polymerization under visible light. Resultant PEG coatings are over 100
um thick and localized to microcarrier surfaces. This thickness is relevant for
cells to react to mechanical properties of the hydrogel coating, and coated
microcarriers support hMSC attachment and expansion. hMSC expansion is highly
favorable on coated microcarriers in serum-free media, with doubling times under
25 h in the growth phase, and retained osteogenic and adipogenic differentiation
capacity after culture on microcarriers. These microcarriers with defined,
synthetic coatings enable tailorable surfaces for cell expansion that may be
suitable for a variety of biomanufacturing applications.
PMID- 28509414
TI - The Normal Fetal Pancreas.
AB - OBJECTIVES: The aim of the study was to assess the sonographic feasibility of
measuring the fetal pancreas and its normal development throughout pregnancy.
METHODS: We conducted a cross-sectional prospective study between 19 and 36
weeks' gestation. The study included singleton pregnancies with normal pregnancy
follow-up. The pancreas circumference was measured. The first 90 cases were
tested to assess feasibility. RESULTS: Two hundred ninety-seven fetuses of
nondiabetic mothers were recruited during a 3-year period. The overall
satisfactory visualization rate was 61.6%. The intraobserver and interobserver
variability had high interclass correlation coefficients of of 0.964 and 0.967,
respectively. A cubic polynomial regression described best the correlation of
pancreas circumference with gestational age (r = 0.744; P < .001) and significant
correlations also with abdominal circumference and estimated fetal weight
(Pearson r = 0.829 and 0.812, respectively; P < .001). Modeled pancreas
circumference percentiles for each week of gestation were calculated. During the
study period, we detected 2 cases with overgrowth syndrome and 1 case with an
annular pancreas. CONCLUSIONS: In this study, we assessed the feasibility of
sonography for measuring the fetal pancreas and established a normal reference
range for the fetal pancreas circumference throughout pregnancy. This database
can be helpful when investigating fetomaternal disorders that can involve its
normal development.
PMID- 28509416
TI - The importance of CD39, CD43, CD81, and CD95 expression for differentiating B
cell lymphoma by flow cytometry.
AB - BACKGROUND: B cell lymphomas' (BCL) current diagnosis is usually based on a
combination of morphology, immunophenotype, recurrent cytogenetic aberration and
clinical features. However, even with these diagnostic tools, a definitive
diagnosis can be difficult to achieve. Therefore, the aim of this study was to
assess the profile of CD39, CD43, CD81, and CD95 expressions in diffuse large B
cell lymphoma (DLBCL), follicular lymphoma (FL), and Burkitt lymphoma (BL) cases.
METHODS: To address this issue, we investigated the expression of CD39, CD43,
CD81, and CD95 by eight-color flow cytometry in retrospective cases from 2014 to
2016. RESULTS: The study included 27 adult patients diagnosed with DLBCL, FL, and
BL during the study period. Four patients were diagnosed with germinal center B
cell-like DLBCL (GCB DLBCL), seven with non-GCB DLBCL, nine with FL, and seven
with BL. CD39 seems to be especially relevant to differentiate non-GCB DLBCL from
BL and from FL. BL showed stronger expression of CD43 when compared to FL and GCB
DLBCL. Moreover, CD43 may help to distinguish non-GCB DLBCL from GCB DLBCL. CD81
expression was much stronger in BL when compared to the other three groups of
patients. Lastly, CD95 may also help to distinguish BL from the other subtypes,
as BL cells expressed this antigen at low levels. CONCLUSIONS: In combination,
CD39, CD43, CD81, and CD95 expressions appear to be helpful to distinguish CD10+
BCL, particularly BL. Phenotypic distinction between FL and GCB DLBCL remains
challenging and requires further studies. (c) 2017 International Clinical
Cytometry Society.
PMID- 28509415
TI - Ratings of affective and interpersonal tendencies differ for grandiose and
vulnerable narcissism: A replication and extension of Gore and Widiger (2016).
AB - OBJECTIVE: Theoretical conceptions of narcissism have long been characterized by
two seemingly opposing poles: grandiosity and vulnerability. The goal of the
current study was to investigate the extent to which traits associated with one
profile are perceived to co-occur with the other within an individual. METHOD:
Lay raters (N = 862; 56% female; 80% Caucasian; Mage = 37) recruited from
Amazon's MTurk were assigned to one of four conditions in which they rated how
often a series of narcissistic traits were displayed by a prototypical grandiose
narcissist, a vulnerable narcissist, a close friend, or themselves. Vulnerable
narcissism items were specifically worded to assess internalizing- versus
externalizing-based emotional responses. RESULTS: Results suggest that
grandiosely narcissistic individuals are seen as responding angrily to ego
threatening situations, whereas vulnerably narcissistic individuals are seen as
responding with a broader array of negative emotions, including anger, sadness,
and shame. In contrast, vulnerably narcissistic individuals were not rated as
consistently demonstrating behaviors, attitudes, or cognitions associated with
grandiose narcissism. CONCLUSIONS: Grandiose and vulnerable narcissistic
individuals both exhibit anger in response to ego threat, but sadness/shame
responses are more characteristic of vulnerable narcissism.
PMID- 28509417
TI - Overexpression of ubiquitin specific peptidase 14 predicts unfavorable prognosis
in esophageal squamous cell carcinoma.
AB - BACKGROUND: Ubiquitin specific peptidase 14 (USP14), a deubiquitinating enzyme,
has been documented as a key element to regulate the proteolysis function of
proteasomes and an attractive therapeutic target for several cancers. Herein, we
elucidate the role of USP14 in predicting the prognosis of patients with
esophageal squamous cell carcinoma (ESCC). METHODS: USP14 expression was detected
in ESCC tissues and matched adjacent non-tumorous tissues by quantitative real
time reverse transcription-PCR and immunohistochemistry. Kaplan-Meier survival
analysis was used to assess the correlation between USP14 expression and
prognosis in ESCC patients. Univariate and multivariate analysis was conducted
with a Cox proportional hazards model to determine whether USP14 is an
independent prognostic factor. RESULT: Overexpression of USP14 was observed in
approximately 60% of tested ESCC samples compared to their paired non-tumor
esophageal tissues at both RNA and protein levels, and was significantly
associated with distant metastasis (P = 0.001). Kaplan-Meier analysis showed that
USP14 overexpression was related to poorer overall patient survival. Univariate
and multivariate analyses demonstrated that USP14 was an independent risk factor
for overall survival. CONCLUSION: The findings in this study suggest that USP14
could be used as a potential prognostic marker for ESCC patients.
PMID- 28509418
TI - Sirenomelia: A Multi-systemic Polytopic Field Defect with Ongoing Controversies.
AB - The most impressive phenotypic appearance of sirenomelia is the presence of a 180
degrees -rotated, axially positioned, single lower limb. Associated
gastrointestinal and genitourinary anomalies are almost always present. This rare
anomaly is still the subject of ongoing controversies concerning its nosology,
pathogenesis, and possible genetic etiology. Sirenomelia can be part of a
syndromic continuum, overlapping with other complex conditions including caudal
dysgenesis and VATER/VACTERL/VACTERL-H associations, which could all be part of a
heterogeneous spectrum, and originate from an early defect in blastogenesis. It
is imaginable that different "primary field defects," whether or not genetically
based, induce a spectrum of caudal malformations. In the current study, we review
the contemporary hypotheses and conceptual approaches regarding the etiology and
pathogenesis of sirenomelia, especially in the context of concomitant conditions.
To expand on the latter, we included the external and internal dysmorphology of
one third trimester sirenomelic fetus from our anatomical museum collection, in
which multiple concomitant but discordant anomalies were observed compared with
classic sirenomelia, and was diagnosed as VACTERL-H association with sirenomelia.
Birth Defects Research 109:791-804, 2017. (c) 2017 The Authors. Birth Defects
Research Published by Wiley Periodicals, Inc.
PMID- 28509420
TI - The magnitude of Indigenous and non-Indigenous oral health inequalities in
Brazil, New Zealand and Australia.
AB - OBJECTIVE: To compare the magnitude of relative oral health inequalities between
Indigenous and non-Indigenous persons from Brazil, New Zealand and Australia.
METHODS: Data were from surveys in Brazil (2010), New Zealand (2009) and
Australia (2004-06 and 2012). Participants were aged 35-44 years and 65-74 years.
Indigenous and non-Indigenous inequalities were estimated by prevalence ratios
(PR) and their corresponding 95% confidence intervals (CI), adjusting for sex,
age and income. Outcomes included inadequate dentition, untreated dental caries,
periodontal disease and the prevalence of "fair" or "poor" self-rated oral health
in Australia and New Zealand, and satisfaction with mouth/teeth in Brazil (SROH).
RESULTS: Irrespective of country, Indigenous persons had worse oral health than
their non-Indigenous counterparts in all indicators. The magnitude of these
ratios was greatest among Indigenous and non-Indigenous Australians, who, after
adjustments, had 2.77 times the prevalence of untreated dental caries (95% CI
1.76, 4.37), 5.14 times the prevalence of fair/poor SROH (95% CI 2.53, 10.43).
CONCLUSION: Indigenous people had poorer oral health than their non-Indigenous
counterparts, regardless of setting. The magnitude of the relative inequalities
was greatest among Indigenous Australians for untreated dental decay and poor
SROH.
PMID- 28509419
TI - Live-cell CRISPR imaging in plants reveals dynamic telomere movements.
AB - Elucidating the spatiotemporal organization of the genome inside the nucleus is
imperative to our understanding of the regulation of genes and non-coding
sequences during development and environmental changes. Emerging techniques of
chromatin imaging promise to bridge the long-standing gap between sequencing
studies, which reveal genomic information, and imaging studies that provide
spatial and temporal information of defined genomic regions. Here, we demonstrate
such an imaging technique based on two orthologues of the bacterial clustered
regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated
protein 9 (Cas9). By fusing eGFP/mRuby2 to catalytically inactive versions of
Streptococcus pyogenes and Staphylococcus aureus Cas9, we show robust
visualization of telomere repeats in live leaf cells of Nicotiana benthamiana. By
tracking the dynamics of telomeres visualized by CRISPR-dCas9, we reveal dynamic
telomere movements of up to 2 MUm over 30 min during interphase. Furthermore, we
show that CRISPR-dCas9 can be combined with fluorescence-labelled proteins to
visualize DNA-protein interactions in vivo. By simultaneously using two dCas9
orthologues, we pave the way for the imaging of multiple genomic loci in live
plants cells. CRISPR imaging bears the potential to significantly improve our
understanding of the dynamics of chromosomes in live plant cells.
PMID- 28509421
TI - CRISPR/Cas9-mediated targeted mutagenesis of GmFT2a delays flowering time in soya
bean.
AB - Flowering is an indication of the transition from vegetative growth to
reproductive growth and has considerable effects on the life cycle of soya bean
(Glycine max). In this study, we employed the CRISPR/Cas9 system to specifically
induce targeted mutagenesis of GmFT2a, an integrator in the photoperiod flowering
pathway in soya bean. The soya bean cultivar Jack was transformed with three
sgRNA/Cas9 vectors targeting different sites of endogenous GmFT2a via
Agrobacterium tumefaciens-mediated transformation. Site-directed mutations were
observed at all targeted sites by DNA sequencing analysis. T1-generation soya
bean plants homozygous for null alleles of GmFT2a frameshift mutated by a 1-bp
insertion or short deletion exhibited late flowering under natural conditions
(summer) in Beijing, China (N39 degrees 58', E116 degrees 20'). We also found
that the targeted mutagenesis was stably heritable in the following T2
generation, and the homozygous GmFT2a mutants exhibited late flowering under both
long-day and short-day conditions. We identified some 'transgene-clean' soya bean
plants that were homozygous for null alleles of endogenous GmFT2a and without any
transgenic element from the T1 and T2 generations. These 'transgene-clean'
mutants of GmFT2a may provide materials for more in-depth research of GmFT2a
functions and the molecular mechanism of photoperiod responses in soya bean. They
will also contribute to soya bean breeding and regional introduction.
PMID- 28509422
TI - Evaluation of the Medicinal Potential of Two Ruthenium(II) Polypyridine Complexes
as One- and Two-Photon Photodynamic Therapy Photosensitizers.
AB - Two [Ru(phen)2 dppz]2+ derivatives (phen=1,10-phenantroline, dppz=dipyrido[3,2
a:2',3'-c]phenazine) with different functional groups on the dppz ligand [dppz
7,8-(OMe)2 (1), dppz-7,8-(OH)2 (2)] have been synthesized, characterized and
investigated as photosensitizers (PSs) for photodynamic therapy (PDT) against
cancer. Both complexes showed intense red phosphorescence and promising singlet
oxygen (1 O2 ) quantum yields of 75 % (1) and 54 % (2) in acetonitrile. Complex 1
(logPo/w =-0.52, 2.4 nmol Ru per mg protein) was found to be more lipophilic,
having also a higher cellular uptake efficiency compared to 2 (logPo/w =-0.20,
0.9 nmol Ru per mg protein). Complex 1 localized evenly in HeLa cells whereas 2,
was mainly visualized in the cell membrane by confocal microscopy. In the dark,
complex 1 (IC50 =36.5 MUm) was found to be more toxic than complex 2 (IC50 >100
MUm) on a HeLa cells monolayer. Importantly, in view of PDT applications, both
complexes were found to be non-toxic in the dark towards multicellular HeLa
spheroids (IC50 >100 MUm). Upon one-photon irradiation (420 nm, 9.27 J cm-2 ), 1
exhibited higher phototoxicity (IC50 =3.1 MUm) than 2 (IC50 =16.7 MUm) on HeLa
cell monolayers. When two-photon irradiation (800 nm, 9.90 J cm-2 ) was applied,
only 1 (IC50 =9.5 MUm) was found to be active toward HeLa spheroids. This study
demonstrates that the functional group on the intercalative ligand has a strong
influence on the cellular localization and anticancer activity of RuII
polypyridyl complexes.
PMID- 28509423
TI - Analysis of the relationship between the double transverse foramen and the
possibility of developing clinical symptoms after whiplash.
AB - Currently, there is no information about the possibility of developing clinical
symptoms after whiplash in double transverse foramen subjects. Our aim was to
test whether subjects with double transverse foramen have an increased risk of
presenting with an acute headache, dizziness, vertebral artery dissection, and
vomiting after whiplash.We recorded the absence/presence of double transverse
foramen, and the absence/presence of neck pain, acute headache, dizziness,
vertebral artery dissection, and vomiting in 85 patients who had suffered
whiplash injuries in car rear-end impacts in road traffic accidents. We used the
odds ratio test to determine whether double transverse foramen subjects are at a
higher risk of developing an acute headache, dizziness, and vomiting than non
double transverse foramen subjects.Although double transverse foramen subjects
presented with more clinical symptoms after whiplash, the odds ratio test
revealed that their risks of developing acute headache (P = 0.30), dizziness (P =
0.09), or vomiting (P = 0.18) were not significantly greater than in the control
group.Double transverse foramen subjects are not at a higher risk of presenting
acute headache, dizziness, vertebral artery dissection, and vomiting after
whiplash. Clin. Anat. 30:761-766, 2017. (c) 2017Wiley Periodicals, Inc.
PMID- 28509424
TI - Inhibition of Prion Propagation by 3,4-Dimethoxycinnamic Acid.
AB - Neurodegenerative diseases are associated with accumulation of amyloid-type
protein misfolding products. Prion protein (PrP) is known for its ability to
aggregate into soluble oligomers that in turn associate into amyloid fibrils.
Preventing the formation of these infective and neurotoxic entities represents a
viable strategy to control prion diseases. Numerous attempts to find dietary
compounds with anti-prion properties have been made; however, the most promising
agent found so far was curcumin, which is poorly soluble and merely bioavailable.
In the present work, we identify 3,4-dimethoxycinnamic acid (DMCA) which is a
bioavailable coffee component as a perspective anti-prion compound. 3,4
Dimethoxycinnamic acid was found to bind potently to prion protein with a Kd of
405 nM. An in vitro study of DMCA effect on PrP oligomerization and
fibrillization was undertaken using isothermal titration calorimetry (ITC),
dynamic light scattering (DLS) and circular dichroism (CD) methodologies. We
demonstrated that DMCA affects PrP oligomer formation reducing the oligomer
content by 30-40%, and enhancing SH-SY5Y cell viability treated with prion
oligomers. Molecular docking studies allowed to suggest a site where DMCA is able
to bind stabilizing PrP tertiary structure. We suggest that DMCA is a perspective
dietary compound for prophylaxis of neurodegenerative diseases that needs further
research. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28509425
TI - Methods of fixation of intraocular lenses according to the anatomical structures
in trauma eyes.
AB - Ocular trauma can lead to severe visual impairment and morbidity, depending on
the anatomical structures affected. The main causes of ocular trauma include
foreign bodies, impact by an object, falls, and chemicals. Most ocular traumas
occur in children or young male adults. A meticulous slit lamp examination is
crucial for assessing all anatomical structures. Trauma to the crystalline lens
can result in dislocation, an intralenticular foreign body, cataract,
fragmentation, and capsular breach. An intraocular lens (IOL) can endure
subluxation or luxation under the conjunctiva, into the anterior chamber or the
vitreous, or can be extruded. The surgical approach depends on the condition and
morphology of the lens and the anatomical structures surrounding it. If there is
capsular bag support, a secondary IOL can be placed in the sulcus using remnants
of the damaged capsule. If there is no capsular bag support, a secondary IOL can
be fixated to the anterior chamber angle, to the iris, or to the sclera. A
detailed history of injury cannot always be obtained in trauma settings. Proper
education, supervision, and certified safety eye protectors could prevent up to
90% of ocular injuries. Lens trauma can be treated with various surgical
procedures and fixation techniques, which nevertheless require advanced surgical
skills owing to the fine anatomical structure of the anterior segment. A careful
surgical strategy should be established for a globe reconstruction after trauma
with secondary lens implantation. Clin. Anat. 31:6-15, 2018. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28509427
TI - Self-Supplying O2 through the Catalase-Like Activity of Gold Nanoclusters for
Photodynamic Therapy against Hypoxic Cancer Cells.
AB - Photodynamic therapy (PDT) typically involves oxygen (O2 ) consumption and
therefore suffers from greatly limited anticancer therapeutic efficacy in tumor
hypoxia. Here, it is reported for the first time that amine-terminated, PAMAM
dendrimer-encapsulated gold nanoclusters (AuNCs-NH2 ) can produce O2 for PDT via
their intrinsic catalase-like activity. The AuNCs-NH2 not only show optimum H2 O2
consumption via the catalase-like activity over the physiological pH range (i.e.,
pH 4.8-7.4), but also extend such activity to acidic conditions. The possible
mechanism is deduced from that the enriched tertiary amines of dendrimers are
easily protonated in acidic solutions to facilitate the preadsorption of OH on
the metal surface, thereby favorably triggering the catalase-like reaction. By
taking advantage of the exciting feature on AuNCs-NH2 , the possibility to supply
O2 via the catalase-like activity of AuNCs-NH2 for PDT against hypoxia of cancer
cells was further studied. This proof-of-concept study provides a simple way to
combine current O2 -dependent cancer therapy of PDT to overcome cancer cell
hypoxia, thus achieving more effective anticancer treatments.
PMID- 28509426
TI - Precise Patterning of Organic Single Crystals via Capillary-Assisted Alternating
Electric Field.
AB - Owing to the extraordinary properties, organic micro/nanocrystals are important
building blocks for future low-cost and high-performance organic electronic
devices. However, integrated device application of the organic micro/nanocrystals
is hampered by the difficulty in high-throughput, high-precision patterning of
the micro/nanocrystals. In this study, the authors demonstrate, for the first
time, a facile capillary-assisted alternating-electric field method for the large
scale assembling and patterning of both 0D and 1D organic crystals. These
crystals can be precisely patterned at the photolithography defined
holes/channels at the substrate with the yield up to 95% in 1 mm2 . The mechanism
of assembly kinetics is systematically studied by the electric field distribution
simulation and experimental investigations. By using the strategy, various
organic micro/nanocrystal patterns are obtained by simply altering the geometries
of the photoresist patterns on substrates. Moreover, ultraviolet photodetectors
based on the patterned Alq3 micro/nanocrystals exhibit visible-blind
photoresponse with high sensitivity as well as excellent stability and
reproducibility. This work paves the way toward high-integration, high
performance organic electronic, and optoelectronic devices from the organic
micro/nanocrystals.
PMID- 28509428
TI - Including Langerhans cell histiocytosis in the differential diagnosis of skin
tumors with osteoclast-like multinucleated giant cells.
PMID- 28509429
TI - Chronic kidney disease: A likely underestimated component of multimorbidity in
older patients with chronic obstructive pulmonary disease.
AB - The coexistence of chronic kidney disease and chronic obstructive pulmonary
disease, two age-related conditions, has important clinical and prognostic
implications. Respiratory failure is associated with important changes in
glomerular and tubulointerstitial function. In contrast, renal failure can affect
lung function, mainly by adding a restrictive component or causing complications,
such as uremic pulmonary edema and pleural effusion. The effect of age on renal
and pulmonary function adds to the complexity of the interplay between the kidney
and the lung in these patients. Chronic kidney disease also represents an
important risk factor for adverse drug reactions in older chronic obstructive
pulmonary disease patients in which multimorbidity and polypharmacy are highly
prevalent. Finally, an additive effect of chronic kidney disease and chronic
obstructive pulmonary disease might also contribute to the pathophysiology of
sarcopenia. Nevertheless, several gaps in our knowledge of the lung-kidney
interplay still exist, thus suggesting further basic and clinical research on
this topic. Geriatr Gerontol Int 2017; 17: 1770-1788.
PMID- 28509430
TI - Trapping CO2 by Adduct Formation with Nitrogen Heterocyclic Carbenes (NHCs): A
Theoretical Study.
AB - Carbon dioxide can form compounds with nitrogen heterocyclic carbenes (NHCs)
based on azoles through noncovalent interactions or by covalent bonding. A narrow
dependence on the carbene structure has been observed for the preference for one
or the other type of bonding, as revealed by a series of physicochemical
descriptors. In our survey, a set of NHCs based on the azole family (three
classical, three abnormal, and one remote) was shown to bind CO2 at the accurate
G4MP2 computational level. In most cases, exothermic reaction profiles towards
the covalently bound form were found, which reached stabilization enthalpies of
up to -77 kJ mol-1 for the remote carbene case. Both noncovalent and covalent
minima and the corresponding transition state that connects them have been
identified as stationary points along the reaction coordinate.
PMID- 28509431
TI - Golga5 is dispensable for mouse embryonic development and postnatal survival.
AB - Golgins are a family of coiled-coil proteins located at the cytoplasmic surface
of the Golgi apparatus and have been implicated in maintaining Golgi structural
integrity through acting as tethering factors for retrograde vesicle transport.
Whereas knockdown of several individual golgins in cultured cells caused Golgi
fragmentation and disruption of vesicle trafficking, analysis of mutant mouse
models lacking individual golgins have discovered tissue-specific developmental
functions. Recently, homozygous loss of function of GOLGA2, of which previous in
vitro studies suggested an essential role in maintenance of Golgi structure and
in mitosis, has been associated with a neuromuscular disorder in human patients,
which highlights the need for understanding the developmental roles of the
golgins in vivo. We report here generation of Golga5-deficient mice using
CRISPR/Cas9-mediated genome editing. Although knockdown studies in cultured cells
have implicated Golga5 in maintenance of Golgi organization, we show that Golga5
is not required for mouse embryonic development, postnatal survival, or
fertility. Moreover, whereas Golga5 is structurally closely related to Golgb1, we
show that inactivation of Golga5 does not enhance the severity of developmental
defects in Golgb1-deficient mice. The Golga5-deficient mice enable further
investigation of the roles and functional specificity of golgins in development
and diseases.
PMID- 28509432
TI - Feasibility assessment of shear wave elastography to lumbar back muscles: A
Radioanatomic Study.
AB - Low back pain is often associated with tensional changes in the paraspinal
muscles detected by palpatory procedures. Shear wave elastography (SWE), recently
introduced, allows the stiffness of muscles to be assessed noninvasively. The aim
of this work was to study the feasibility of using SWE on the three main lumbar
back muscles (multifidus, longissimus, and iliocostalis) in vivo after analyzing
their muscular architecture ex vivo. We determined the orientation of fibers in
the multifidus, longissimus, and iliocotalis muscles in seven fresh cadavers
using gross anatomy and B-Mode ultrasound imaging. We then quantified the
stiffness of these three muscles at the L3 level ex vivo and in 16 healthy young
adults. Little pennation was observed in the longissimus and iliocostalis, in
which the direction of fibers was almost parallel to the line of spinous
processes. The multifidus appeared as a multiceps and multipennate muscle. Given
the random layering of millimetric fascicles, tendons, and fatty spaces, the
multifidus had multiple fiber orientations. Muscular fascicles and fibers were
oriented from 9 degrees to 22 degrees to the line of spinous processes. The
shear moduli related to stiffness were 6.9 +/- 2.7 kPa for the longissimus, 4.9
+/- 1.4 kPa for the iliocostalis, and 5.4 +/- 1.6 kPa for the multifidus. SWE is
a feasible method for quantifying the stiffness of the lumbar back muscles. Clin.
Anat. 30:774-780, 2017. (c) 2017Wiley Periodicals, Inc.
PMID- 28509433
TI - Dosing anticancer drugs in infants: Current approach and recommendations from the
Children's Oncology Group's Chemotherapy Standardization Task Force.
AB - An analysis of dose modifications for infants in 29 Children's Oncology Group
protocols across 10 cancer types revealed 11 sets of criteria defining the infant
population using age, weight, body surface area (BSA), or a combination of these
parameters and eight dose modification methods. A new method of dosing anticancer
drugs in infants was developed based on the rationale that prior modifications
were implemented to reduce toxicity, which is not cancer-specific. The new method
uses BSA dose banding in dosing tables for infants and children with a BSA <0.6
m2 and gradually transitions from body weight based to BSA-based dosing.
PMID- 28509434
TI - New liver - Fresh microbiome: Implications on brain function.
PMID- 28509435
TI - Inpatient iron deficiency detection and management: how do general physicians and
gastroenterologists perform in a tertiary care hospital?
AB - BACKGROUND: Iron deficiency (ID) is often an indicator of underlying pathology.
Early detection and treatment avoids long-term morbidity and allows for prompt
iron repletion, avoiding ID anaemia (IDA) and the need for blood transfusion.
AIM: To evaluate the management of ID in two internal medicine units (general
medical (GM) and gastroenterology (GE)) in a large metropolitan hospital and
compare it to international guidelines. METHODS: All consecutive inpatient
admissions in the GM and GE units were retrospectively reviewed until 40 patients
in each service were identified with anaemia and/or microcytic hypochromic blood
counts. Patient records and electronic discharge summaries were then reviewed to
assess the recognition, investigation and management of these abnormalities.
RESULTS: Overall, only 60% (48/80) of the cases of microcytic hypochromic picture
and/or anaemia were recognised. Cases were more likely to be detected under the
GE unit, 77.5% (31/40) versus 42% (17/40) in GM (P < 0.002). Of the 31 recognised
GE cases, 28 (90%) were investigated further with iron studies and/or endoscopic
procedures. ID was confirmed in nearly half (5/11) of those tested; however, only
2 of 5 received iron replacement. Among GM patients, only 11 of the 17 recognised
cases (64%) were investigated further. Iron studies were performed in all 11,
confirming IDA in 4 (36%), all of whom received intravenous iron. A faecal human
haemoglobin test was performed in two GM patients and one GE patient. CONCLUSION:
There remains significant room for improvement in the recognition, investigation
and management of ID in hospital practice in Australia.
PMID- 28509436
TI - Pollinators shift to nectar robbers when florivory occurs, with effects on
reproductive success in Iris bulleyana (Iridaceae).
AB - Studies have indicated that florivory and nectar robbing may reduce reproductive
success of host plants. However, whether and how these effects might interact
when plants are simultaneously attacked by both florivores and nectar robbers
still needs further investigation. We used Iris bulleyana to detect the
interactions among florivory, nectar robbing and pollination, and moreover, their
effects on plant reproductive success. Field investigations and hand-pollination
treatments were conducted on two experimental plots from a natural population, in
which Experimental plot was protected from florivores and Control plot was not
manipulated. The flower calyx was bitten by sawflies to consume the nectary, and
three bumblebee species were pollinators. In addition, the short-tongued
pollinator, Bombus friseanus, was the only robber when there was a hole made by a
sawfly. The bumblebee had significantly shortened flower handling time when
robbing, as compared to legitimate visits. Pollinator visitation and seed
production decreased significantly in damaged flowers. However, seed production
per flower after supplementary hand-pollination did not differ significantly
between damaged and undamaged flowers. Compared to the Experimental plot,
bumblebees visited fewer flowers per plant in a foraging bout in the Control
plot. The flowers damaged by florivory allowed B. friseanus to shift to a nectar
robber. Florivory and nectar robbing collectively decreased plant reproductive
success by consuming nectar resources, which may reduce attractiveness to
pollinators of the damaged flowers. However, the changes in pollinator behaviour
might be beneficial to the plant by reducing the risk of geitonogamous mating.
PMID- 28509437
TI - Detection of Avian Influenza Virus from Cloacal Swabs Using a Disposable Well
Gate FET Sensor.
AB - Current methods to detect avian influenza viruses (AIV) are time consuming and lo
inw sensitivity, necessitating a faster and more sensitive sensor for on-site
epidemic detection in poultry farms and urban population centers. This study
reports a field effect transistor (FET) based AIV sensor that detects
nucleoproteins (NP) within 30 minutes, down to an LOD of 103 EID50 mL-1 from a
live animal cloacal swab. Previously reported FET sensors for AIV detection have
not targeted NPs, an internal protein shared across multiple strains, due to the
difficulty of field-effect sensing in a highly ionic lysis buffer. The AIV sensor
overcomes the sensitivity limit with an FET-based platform enhanced with a
disposable well gate (DWG) that is readily replaceable after each measurement. In
a single procedure, the virus-containing sample is immersed in a lysis buffer
mixture to expose NPs to the DWG surface. In comparison with commercial AIV rapid
kits, the AIV sensor is proved to be highly sensitive, fast, and compact, proving
its potential effectiveness as a portable biosensor.
PMID- 28509439
TI - Structure-Activity Relationship Studies of the Cyclic Depsipeptide Natural
Product YM-254890, Targeting the Gq Protein.
AB - Extracellular signals perceived by G protein-coupled receptors are transmitted
via G proteins, and subsequent intracellular signaling cascades result in a
plethora of physiological responses. The natural product cyclic depsipeptides YM
254890 and FR900359 are the only known compounds that specifically inhibit
signaling mediated by the Gq subfamily. In this study we exploit a newly
developed synthetic strategy for this compound class in the design, synthesis,
and pharmacological evaluation of eight new analogues of YM-254890. These
structure-activity relationship studies led to the discovery of three new
analogues, YM-13, YM-14, and YM-18, which displayed potent and selective Gq
inhibitory activity. This provides pertinent information for the understanding of
the Gq inhibitory mechanism by this class of compounds and importantly provides a
pathway for the development of labeled YM-254890 analogues.
PMID- 28509438
TI - Deguelin inhibits epithelial-to-mesenchymal transition and metastasis of human
non-small cell lung cancer cells by regulating NIMA-related kinase 2.
AB - BACKGROUND: Non-small cell lung cancer is a lethal malignancy with a high
mortality rate. Deguelin displays an anti-tumor effect and inhibits metastasis in
various cancers. The aberrant expression of NIMA-related kinase 2 (NEK2)
indicates poor prognosis and induces epithelial-to-mesenchymal transition (EMT)
and metastasis processes. However, the underlying mechanism between deguelin and
NEK2 has remained elusive. METHODS: NSCLC cell lines were treated with deguelin.
Wound-healing and invasion assays were applied to study the inhibitory effect of
deguelin on NSCLC cells. EMT markers, E-cadherin and Vimentin, were also detected
by Western blot. NEK2 protein and messenger RNA expression levels were evaluated
when NSCLC cells were treated with different concentrations of deguelin. The
effect of NEK2 on NSCLC cell metastasis was evaluated through NEK2 knockdown. To
investigate whether deguelin induced EMT by regulating NEK2, we overexpressed
NEK2 in both NCI-H520 and SK-MES-1 cell lines, and then used real time-PCR to
study the E-cadherin and Vimentin messenger RNA expression in both NSCLC cells.
RESULTS: Deguelin inhibited migration and invasion processes in NSCLC cell lines
and decreased NEK2 expression in a concentration-dependent manner. Furthermore,
NEK2 knockdown inhibited NSCLC cell migration and invasion. Finally,
overexpressing NEK2 in NCI-H520 and SK-MES-1 cells could restore the inhibition
of metastasis induced by deguelin. CONCLUSIONS: Deguelin could inhibit EMT and
metastasis, while overexpression of NEK2 promotes these processes. Deguelin could
decrease NEK2 expression, while NEK2 overexpression could restore deguelin
induced inhibition of metastasis.
PMID- 28509440
TI - No improvement in clinical trial enrollment for adolescents and young adults with
cancer at a children's hospital.
AB - BACKGROUND: We have previously published data from 2001 to 2006 showing that
adolescent and young adult (AYA) oncology patients have significantly lower
therapeutic clinical trial enrollment rates than younger patients. Our objective
was to determine if the enrollment of AYA patients on therapeutic studies at the
same institution has improved in recent years with the greater focus on this
population locally and nationally. METHODS: We retrospectively analyzed cancer
registry data at the Children's Hospital of Pittsburgh (CHP) for all new
oncologic diagnoses between January 2010 and December 2014. These data included
age, gender, diagnosis, race and whether the patient was enrolled on an open
treatment study. Univariate analyses were carried out to compare demographic data
between AYA patients (aged 15-22) who enrolled on study and those who did not.
RESULTS: Eight hundred sixty-five new oncology patients were seen at CHP during
this time, 23% of whom were 15 years or older; 33% of all patients were treated
on a clinical trial, including 34% of younger patients and 24% of older patients
(P = 0.0017). The differences between these rates and those from prior years in
both age groups (38% and 27%, respectively) were not statistically significant (P
= 0.15, 0.53). The most common reason for the low enrollment rates was again the
lack of an open therapeutic trial. CONCLUSION: Despite initiatives at CHP and on
the national level to enroll more AYA patients on clinical trials, our most
recent data show no improvement. This is a potentially remediable factor that
needs to continue to be prioritized nationally.
PMID- 28509441
TI - The Greek Registry of Shwachman Diamond-Syndrome: Molecular and clinical data.
AB - This study presents the clinical phenotype and molecular analysis findings from
11 patients recorded in the Greek Shwachman-Diamond syndrome (SDS) Registry. The
most severely affected patient in our registry was diagnosed at birth and is the
first patient reported to require bone marrow transplantation so early in life.
Severe psoriasis, a feature not previously reported in SDS, was observed in one
patient. Mutations in the Shwachman-Bodian-Diamond syndrome gene (SBDS) were
found in all patients. Cytogenetic analyses revealed clonal abnormalities, one
novel, in two patients.
PMID- 28509442
TI - Self-Assembled Nanoparticles from Phenolic Derivatives for Cancer Therapy.
AB - Therapeutic nanoparticles hold clinical promise for cancer treatment by avoiding
limitations of conventional pharmaceuticals. Herein, a facile and rapid method is
introduced to assemble poly(ethylene glycol) (PEG)-modified Pt prodrug
nanocomplexes through metal-polyphenol complexation and combined with
emulsification, which results in ~100 nm diameter nanoparticles (PtP NPs) that
exhibit high drug loading (0.15 fg Pt per nanoparticle) and low fouling
properties. The PtP NPs are characterized for potential use as cancer
therapeutics. Mass cytometry is used to quantify uptake of the nanoparticles and
the drug concentration in individual cells in vitro. The PtP NPs have long
circulation times, with an elimination half-life of ~18 h in healthy mice. The in
vivo antitumor activity of the PtP NPs is systematically investigated in a human
prostate cancer xenograft mouse model. Mice treated with the PtP NPs demonstrate
four times better inhibition of tumor growth than either free prodrug or
cisplatin. This study presents a promising strategy to prepare therapeutic
nanoparticles for biomedical applications.
PMID- 28509443
TI - Haemodynamically stimulated and in vivo generated axially vascularized soft
tissue free flaps for closure of complex defects: Evaluation in a small animal
model.
AB - The arteriovenous (AV) loop model permits the creation of significant volumes of
axially vascularized tissue that represents an alternative to conventional free
flaps, circumventing their common limitations. However, such AV loop-based flaps
have never before been examined in standardized animal models with respect to
their suitability for reconstruction of critical bone-exposing defects. In the
course of our preliminary studies, we implemented a novel defect model in rats
that provides standardized and critical wound conditions and evaluated whether AV
loop-generated flaps are suitable for free microsurgical transfer and closure of
composite defects. We compared three groups of rodents with similar scapular
defects: one received the AV flap, whereas controls were left to heal by
secondary intention or with supplementary acellular matrix alone. To create the
flaps, AV loops were placed into subcutaneous Teflon chambers filled with
acellular matrix and transferred to the thigh region. Flap maturation was
evaluated by histological analysis of angiogenesis and cell migration at days 14
and 28 after loop creation. Flap transfer to the scapular region and
microsurgical anastomoses were performed after 14 days. Postoperative defect
closure and perfusion were continually compared between groups. Within the AV
flap chamber, the mean vessel number, cell count and the proportion of
proliferating cells increased significantly over time. The novel defect model
revealed that stable wound coverage with homogeneous vascular integration was
achieved by AV loop-vascularized soft-tissue free flaps compared with controls.
In summary, our study indicates for the first time that complex composite defects
in rats can successfully be treated with AV loop-based free flaps.
PMID- 28509444
TI - [Demographic aspects of population aging in Saint-Petersburg at the end of XX-the
beginning of XXI century. Part I. Conventional aging measures].
AB - The paper represents the first part of the series of two articles on demographic
aspects of population aging in Saint-Petersburg in 1990-2010 compared to the
situation in the Russian Federation as a whole. In the first part, the situation
with the population aging in Saint-Petersburg and Russia is considered based on
traditional aging measures - the proportion of elderly in the total population,
aging index, old age dependency rate and the parents support ratio. In the second
part, a number of prospective aging indicators that take account of remaining
life expectancy, will be studied. The analysis also includes the consideration of
gender imbalance of aging indicators. Accelerating of population aging in Saint
Petersburg and Russia leads to a new demographic situation requiring a number of
economic and socially oriented measures.
PMID- 28509445
TI - [Comparative assessment of aging rates in population from different cities].
AB - 437 people (214 men and 223 women) at the age of 50-90 years old, residents of
different cities of Russia and Pridnestrovie (Moscow, Barnaul, Tiraspol) have
been examined. Using a complex of morphofunctional characteristics, parameters of
the biological age have been analyzed, and groups with delayed, moderate and
accelerated aging rates have been outlined. Regional peculiarities in
distribution of incidence of different variants of aging rates have been
revealed. In Moscow men and women, the delayed variant of development of age
involution changes is the most widespread. In Tiraspol women, compared to the
Moscow group, incidence of people with accelerated aging rates is 2 times higher,
which can be stipulated by influence of a complex of biosocial factors.
PMID- 28509446
TI - [Stochastic simulation of the process of matching of the ages of the human and
the experimental mammalian].
AB - The aim of the article is to work out the simple approach for matching of the
ages of the human and mammalian. The model is based on the analysis of the
counting processes of the proper ontogenetic events (such as the emergence of the
first molars, the first ovulation, almost complete cessation of growth,
menopause). The choice of the events is reduced to the claim of being observable.
The matching (and proper concordance) are useful for the choice of the individual
regimens of medical treatment.
PMID- 28509447
TI - [Discontinuity of the annuity curves. I. Departures from Gompertz law in
Drosophila melanogaster Canton-S strain].
AB - Analysis of male imago mortality in Drosophila melanogaster Canton-S strain
demonstrated deviation from Gompertz law. Annuity curves were composed of five
phases divided by sharp bends. All the phases seemed to be linear. We discuss the
hypotheses of strict genetic determination of the phenomenon.
PMID- 28509448
TI - [Influence of changes in the reproductive behavior on the average duration of the
reproductive period and life span].
AB - This article explains the model of changing the duration of the reproductive
period and life span under the influence of the demographic trend towards an
increase in age at first birth in modern developed countries. Acting as a factor
of artificial selection, increase parental age may lead to a shift of the upper
boundary of the reproductive period in the new generations, and life expectancy.
The article discusses the role of a number of social factors to identify trends.
PMID- 28509449
TI - [Modern directions of scientific and practical research of the policy of active
and healthy longevity: experience and perspectives].
AB - Modern terminology on active and healthy aging used in scientific and project
activities is discussed. There have been analyzed the WHO conception on active
aging, which has no precise universally agreed definition, its main determinants.
The directions of scientific expertise in the major European projects INNOVAGE -
assessment of potentially profitable social innovations relating to the welfare
and quality of life and health in old age; MOPACT - the interference between the
demographic development and the main dimensions of economic and social
contribution of older persons is defined. The approach to implement the policy of
active and healthy longevity as a valuable asset of the modern society is
underlined.
PMID- 28509450
TI - [Socio-psychological grading in gerontology].
AB - Senior and senile age is characterized by psychological, social and somatic
heterogeneity of patients. To ensure high level of quality of life and to
optimize the functioning of staff of geriatric hospitals we propose to introduce
the distribution of pensioners within departments based on their psychosomatic
status. On the analogy of the "medical triage", authors propose to introduce
socio-psychological grading of older persons living in geriatric centers,
focusing on their ability for self-care, the degree of preservation of cognitive
functions, individual psychological characteristics. Testing of this grading was
made on the basis of the Scientific and Methodological Gerontological Center. As
a result of introduction of the principle of socio-psychological grading,
positive dynamics in the psychological state of patients, better performance of
the staff, and improved subjective assessment of the quality of life of older
persons were registered.
PMID- 28509451
TI - [Physiological aspects of music and longevity].
AB - The article provides an overview of the results of studies on the effect of music
on the function of various physiological systems of the organism including the
nervous, cardiovascular and endocrine systems, also on the effect of Mozart's
music and the later mature Baroque music. Particular attention is paid to
information on the influence of different kinds of music (classical, jazz and
rock), of the nature and of the degree of musical activity (listeners, amateurs
and professional performers) on cognitive and behavioral function, on health
status, life expectancy and longevity. Structural acoustical attributes of music
defining its treatment effect, are described with the comparison of aspects of
rock music and of classical music. The article also considers the prospects for
using of music in the treatment and prevention of age-associated diseases.
PMID- 28509452
TI - [Adhesion molecule JAM-A, its function and mechanism of epigenetic regulation].
AB - The article represents evidence about structures, properties and functions of
adhesion molecule JAM-A/1 belonging to JAM subfamily. This protein plays an
important role in epithelial tight junction formation and immune function.
Current article focuses on the role of JAM-A protein in pathogenesis associated
to ageing: atherosclerosis, apoplexy, thrombosis, hypertension, ophthalmological
pathology. We propose short peptides Lys-Glu, Lys-Glu-Asp, and Ala-Glu-Asp-Gly
could influence on F11R gene expression that leads to recovery of JAM-A synthesis
in cells.
PMID- 28509453
TI - [Central female hypogonadism as a model of premature aging].
AB - Central (hypogonadotropic) hypogonadism in women could also be a cause of
persistent amenorrhea and hypoestrogenemia. The aim of this study was to evaluate
symptoms of premature aging in women of young age with central hypogonadism. 88
young women (25 [21; 30] y.o.) with central hypogonadism (with isolated
hypogonadotropic hypogonadism n=42, and associated with the other types of
pituitary insufficiencies n=46), 53 healthy young women (24 [23; 28] y.o.) and 50
healthy postmenopausal women (56 [53; 58] y.o.) were examined. In young women
with central hypogonadism frequency of psychoemotional, neurovegetative and
urogenital disorders, peripheral sex steroid concentrations, lipid and mineral
homeostasis parameters differed significantly from the healthy young women of
similar age and were comparable with postmenopausal women of middle/older age.
Thus, according to clinical, hormonal and biochemical abnormalities biological
age of female patients with central hypogonadism advanced significantly
chronological young age and corresponded to middle/older age. The central female
hypogonadism is a model of premature aging.
PMID- 28509454
TI - [Monoamine oxidase activity in rat pineal gland: comparison with brain areas,
alteration during aging].
AB - Using benzylamine as a substrate, the amine oxidase activity was determined in
the pineal gland of adult rats and compared with the same activity in brain areas
and pituitary. Two groups of rats aged 6-8 and 14-15 months were also compared on
the basis of this activity. Benzylamine deaminating activity in the pineal gland
was significantly higher than in the area preoptica medialis, the corpus
mamillare, the tuberculum olfactorium, and the hypophysis, and lower than in the
eminentia mediana. The significant increase of the activity in the pineal gland
in animals of age from 6-8 to 14-15-months was revealed. Benzylamine deaminating
activity in the pineal gland was totally inhibited by 0,002 mM R deprenyl,
indicating the B type monoamine oxidase (MAO B) activity. Age-associated increase
of MAO B activity in the pineal gland accompanied by decrease of glutathione
peroxidase activity, reported earlier, can promote the oxidative damage in the
pineal gland during aging.
PMID- 28509455
TI - [Transport function of the lymph nodes in young and old animals].
AB - The paper discusses the age-related changes of contractile activity of the
capsule of the lymph nodes, underlying their transport function. The results of
the studies conducted on the mesenteric lymph nodes of young and old bulls are
presented. The changes in the contractile function of the capsule of the lymph
nodes were revealed in the older animals. The changes appeared in the decrease of
the amplitude and increase of the phase contraction frequency which are based on
the replacement of smooth muscle by connective tissue, the enhancement of
pacemaker activity of smooth muscle cells and endothelial dysfunction of lymph
node cells.
PMID- 28509456
TI - [The morphological changes of Hassall corpuscles of the different maturity in
vertebrate animals and human in different stages of age].
AB - With the use of methods of light microscopy we produce comparison morphological
investigation of Hassall corpuscles of different maturity in animals and human
with age difference. It was arranged that quantity and sizes of Hassall
corpuscles in different stages of age depend on organization level, belonging to
a vital form, shape and age of animal. On the base of our investigation we can
make resume about functional role of Hassall corpuscles.
PMID- 28509458
TI - [Melatonin in a woman's life: from birth to menopause].
AB - We did a review of the literature data of main Russian publications and databases
PubMed/Medline for the last 7 years. In the present article we examine the
physiology of secretion of pineal hormone melatonin and its role in the vital
processes of the body. The study was focused on the influence of melatonin on the
female reproductive system, participation in the aging process and the formation
of pathological menopause. The article presents research data on the
effectiveness of the drug melatonin in the climacteric syndrome. It is revealed
that up to the present time according to the literature data there is no
information about the standards of secretion of melatonin for women of different
age groups, and the lack of secretion of melatonin can be judged by clinical
manifestations, and also when compared with groups of healthy women. Remain
unclear issues in the application of drugs melatonin at various complications of
pregnancy and gynecological diseases. Long-term use of melatonin is still open in
climacteric syndrome.
PMID- 28509457
TI - [Urine proteome study for the evaluation of age dynamics in healthy men].
AB - We investigated the age dynamics of proteomic profile of urine in 52 healthy men
aged 18 to 51 years. A special sample preparation was performed, followed by
liquid chromatography-mass spectrometry. Liquid chromatography-mass spectrometry
of the minor proteins was performed on a nano-HPLC Agilent 1100 system ("Agilent
Technologies Inc.", USA) in combination with a LTQ-FT Ultra mass spectrometer
("Thermo Electron", Germany). A total of 259 proteins were identified. According
to the TiGER database, a tissue origin was established for 141 proteins and
identified 715 processes in which they participate. We found a significant
positive correlation with age, the number of proteins (R=0,566; p-value=1,24E-05)
and the weight of proteins (R=0,45; p value=8,17E-04). Identified 23 proteins
were significantly more frequent in the urine of subjects with increasing age
(p<0,05), and only one protein - RGSL, Regulator of G protein signaling protein
like (MW 125.69) - less frequently.
PMID- 28509459
TI - [Subclinical hypothyroidism in elderly people].
AB - In this review, we discuss clinical features of subclinical hypothyroidism in the
elderly. The article describes the current diagnosis and treatment modalities of
subclinical thyroid dysfunction in the older age group.
PMID- 28509460
TI - [Changes in serum hormone levels in the middle and gerontic aged inhabitants of
Arkhangelsk due to the gender identity].
AB - The serum hormone levels were studied among middle and gerontic aged residents of
Arkhangelsk by enzyme immunoassay and radioimmunoassay. The significant increase
of follicle-stimulating and luteinizing hormones levels in gerontic aged men was
recorded in the presence of higher concentrations of these hormones in women.
There was a statistical tendency of decrease in the level of testosterone in
gerontic aged women compared to middle aged. Regardless of gender the lowering of
the dehydroepiandrosterone sulfate content was observed in gerontic aged
residents compared to middle aged. The criteria of functional activity reduction
of the thyroid gland were a decrease in serum free thyroxine fraction levels in
gerontic aged women and low concentrations of common triiodothyronine in middle
aged men living in Arkhangelsk. Serum cortisol, insulin, estradiol, growth
hormone had no significant age and sex differences in the present groups. The
number of correlations was greater among the gerontic aged people in comparison
with the middle aged, especially among women.
PMID- 28509461
TI - [Age and gender aspects of the status of lipid profile and stress-realizing
systems of the human body in the aging process].
AB - In the course of inspection 1136 persons of different age and sex data on
dynamics of the main components of lipid profile, the concentration of brain
derived neurotrophic factor (BDNF) in blood plasma and indicators of levels of
free cortisol, melatonin sulfate, metanephrine and normetanephrine in urine daily
were obtained. Clear age and gender differences related both to the content of
atherogenic fractions of lipids in the blood, and types of dyslipidemia were
revealed. Fundamental differences in the age dynamics of indicators of stress
realizing systems in men and women and the correlation of these indicators with
the level of low density lipoproteins and atherogenic coefficient were
identified. The data obtained may indicate different mechanisms of development of
atherosclerosis and its associated pathological aging in people of different sex
and age, which enables the practical use of research results for the earliest
diagnosis and prognosis of a number of associated with age and pathological
conditions.
PMID- 28509462
TI - [Musculoskeletal system as a target organ of a frailty processes].
AB - Pathology of the musculoskeletal system is widespread in the population and is
one of the most common diseases of patients in older age groups. The most
significant of them are osteoporosis, osteoarthritis and sarcopenia. All three
components separately, of course, lead to lower quality of life. In our work we
show the mechanisms of interference of these states at each other, and their
combined impact on the musculoskeletal system as a target organ processes senile
asthenia. Osteoarthritis, osteoporosis, and sarcopenia, and especially their
combination lead to hypomobility. Hypomobility under the influence of external
factors is one of the leading syndromes potentiating aggravation processes senile
asthenia. Thus, the mechanism of re-entry is triggered, and a vicious circle
leading to fatal medical-social and social consequences. It is shown that changes
in the musculoskeletal system should be considered as a single aging within
senile asthenia, and all used and newly created medical and social rehabilitation
and prevention programs should be integrated in nature.
PMID- 28509463
TI - [Short and medium-term variability of blood pressure in elderly patients with
arterial hypertension and predicting the risk of renal dysfunction].
AB - The aim of the work was to specifically identify short and medium variability of
blood pressure (BP) in elderly patients with arterial hypertension and to
evaluate the prognostic value of fluctuation of BP for the development of renal
dysfunction. 64 patients with hypertension were surveyed: a core group of 33
patients with start-AG over the age of 60 years, the control group - 31 patients
with uncomplicated hypertension and onset before the age of 60 years. Variability
was evaluated by day, night and diurnal SBP and DBP according to the results of
daily monitoring of blood pressure, as well as intra-individual (short-term) and
visit-to-visit blood pressure variability (seven consecutive days) (medium-term).
The relationship between the parameters of variability of BP and the
characteristics of chronic kidney disease was studied. The elderly hypertension
patients demonstrated a higher short-term and medium-term variability of BP.
Increasing medium variability of systolic BP in advanced aged patients is
associated with the development of chronic kidney disease. When the medium-term
variability of systolic BP exceeds the level of 9,7 mm Hg, the risk of developing
chronic kidney disease increases with a diagnostic sensitivity of 77,1 % and
diagnostic specificity of 80,8 %.
PMID- 28509464
TI - [Features of memory and intellectual activity among the elderly with different
reading productivity].
AB - The aim of this work was the study of indicators of memory and intellectual
activity among the elderly with different reading productivity. The results of
the study showed that the elderly were distinguished by a greater number of
errors when performing tasks on oral-aural, visual memory and visual-spatial
activities. The mistakes made by subjects with low reading productivity may
indicate dysfunction of tone and wakefulness, of receiving, processing and
storing information, as well as weakening of hemispheric interaction.
PMID- 28509465
TI - The evaluation of cognitive skills and the quality of life between Parkinson
Disease patients and healthy aged people above 60 years old.
AB - In the 21st century mankind has made a huge progress in the health care system,
so the average life expectancy has increased significantly compared to the
previous centuries. The managing of healthy ageing of the population represents
one of the main actual problems of the national health care systems around the
world as the aged population is increasing, so, for instance, it is estimated
that there will be over 2 billion people worldwide over the age of 65 by the year
2050 [36]. In particular, the age-related neurological diseases such as Parkinson
Disease (PD) have seen a dramatic increase in international prevalence.
Projections suggest that the neurodegenerative diseases like PD will surpass
cancer as the leading cause of death by the year 2040 [36]; thus presenting an
ever-growing challenge to maintain an optimal quality of life of the patients. In
healthy ageing, cognitive skills impair naturally due to natural brain atrophy;
in PD these processes are rather accelerated, so that, overwhelming clinical
studies showed that dementia eventually develops in up to 80-85 % of patients
with PD [1, 39]. This article is focuses on evaluating the health related quality
of life measurements of PD patients such as cognitive status, anxiety and stress
levels as well as it aims to suggest a possible future strategy to improve the
quality of life of the patients.
PMID- 28509466
TI - [The DC-potential of the brain in older women with postural instability].
AB - The article presents the results of studies of the DC-potential of the brain
level distribution in elderly women with postural instability. Analysis of the DC
potential of the brain level distribution was held by mapping obtained by
measuring the monopolar values of the DC-potential of the brain and calculating
deviations in each of the leads from the average records which were registered in
all areas of the head. It is established that elderly women with postural
instability DC-potential of the brain level distribution are characterized by
increasing in background values and rigid structure of the interaction between
brain regions. The disturbance of the principle of the dome-shaped DC-potential
of the brain level distribution due to the alignment of values for brain regions
was revealed. Factor model with postural instability reflects the control
strengthening over the potential falls from the frontal areas of the brain.
PMID- 28509467
TI - [Age characteristics of the cardiovascular system, depending on the thyroid
function in type 2 diabetes mellitus].
AB - To study the features of cardiovascular system in patients with diabetes mellitus
type 2 considering the thyroid pathology and age, 264 patients were examined.
They were divided into three groups: 1st - patients with diffuse-nodular changes
in the thyroid gland, 2nd - patients with autoimmune thyroid disease, 3rd - a
control group of patients without thyroid disease. The patients of different ages
were examined in each of these groups. All patients were in euthyroid state. It
was established that identified in diabetes mellitus type 2 thyroid pathology and
the thyroid disease contribute special features to the clinical picture for
combined diabetic and cardiovascular pathology even in a euthyroid state
including the age features. The laboratory and instrumental researches showed
that the patients with combined diabetes and thyroid pathology have a higher
incidence of atrial fibrillation, ischemic heart disease, and ventricular
arrhythmias of high grades. They also were noticed to have a more adverse form of
the left ventricle remodeling, also the combination of diastolic and systolic
dysfunctions were found to be more frequent. It was concluded about the necessity
of early diagnosis and correction of the cardiovascular disorders and thyroid
systems in type 2 diabetes mellitus patients, including euthyroid patients.
PMID- 28509468
TI - [Age-related changes of the content of angiomatin and endostatin in human skin].
AB - Human skin structures stained positively for angiomotin or endostatin were
studied by indirect immunohistochemical method. Skin specimens from frontal
surface of the lower part of the neck (from upper corner of standard autopsy skin
incision) from human fetuses died antenatally from 20 to 40 weeks of pregnancy,
humans who died from different causes from 1 day to 85 years of life were
obtained at autopsy. Positive staining for angiomotin or endostatin in the skin
was found in epidermal cells, fibroblasts, sweat and sebaceous glands, blood
vessels of the dermis. Blood vessels stained positively for angiomotin were
detected in skin samples in all ages. Age-dependent decrease in the content of
angiomotin in blood vessels of the dermis was detected. Most prominent decrease
in angiomotin content in dermal blood vessels was found in 61-85 years age-group.
Endostatin positive blood vessels were also detected in skin samples of all ages.
However, the intensity of staining for endostatin in dermal blood vessels was
increased during aging. It can be proposed that changes in the content of
angiomotin and endostatin yield a negative impact on angiogenesis in human skin
during aging.
PMID- 28509469
TI - [The review of the peptides used in dermatocosmetology].
AB - The review of the peptides used in dermatocosmetology is represented. The purpose
of this review is a search of results of the basic scientific researches
confirming or disproving efficiency and/or safety of peptide molecules used in a
modern dermatocosmetology. Questions of forms of application, biological
availability, reliability of the rendered anti-aging effects are considered.
PMID- 28509470
TI - [Treatment of elderly patients with combination of coronary artery disease and
aortic valve pathology].
AB - Increasingly, there are patients with concomitant coronary artery disease and
aortic valve, especially in elderly patients, who often have severe comorbidities
and high surgical risk, which is undoubtedly a certain effect on the choice of
method and tactics of treatment. Today, there are several approaches to the
treatment of patients in this category, and all of them have certain advantages
and disadvantages.
PMID- 28509471
TI - [The study of general satisfaction in stationary social institutions (Yaroslavl
Regional Gerontology Center)].
AB - The article analyzes the satisfaction with social environment of patients of
older age groups living in the Yaroslavl Regional Gerontology Center. On the
basis of a survey of 118 patients of older age groups the satisfaction with the
living conditions in the institution, the provision of socio-medical assistance,
catering, leisure activities and social environment were assessed. 92,4 % of
patients reported of their satisfaction, in general, with the stay. The obtained
information confirms necessity of creation of qualitative therapeutic environment
in a hospital of social service.
PMID- 28509472
TI - [Analysis of indicators of primary disability due to cerebrovascular diseases in
people of retirement age according to the results of medical and social
examination in St. Petersburg].
AB - The article presents data on the primary disability due to cerebrovascular
disease in elderly patients based on the results of the survey in the Bureau of
Medical and Social Expertise of Saint-Petersburg from 2005 to 2014. The analysis
showed a reduction in the indicators of primary disability due to cerebrovascular
disease and the increase in the share of persons with disabilities of the first
and third groups in its structure.
PMID- 28509473
TI - [The issue of quality of Russian cause-specific mortality statistics at old
ages].
AB - The paper presents a brief analysis on the quality of cause-specific mortality
statistics at old ages in Russia. Two aspects are in focus: the regional
differences in approaches for choosing the underlying cause of death and the
comparison of Russian coding practice with the practices of some other European
countries. The results obtained indicate that there are certain problems with the
quality of cause-of-death coding at old ages in Russia. No unified approach to
coding deaths as caused by "Senility" is used at a sub-national level. This leads
to the distortion of the regional cause-specific mortality structures.
Furthermore for many groups of causes Russian death rates are much lower than
those in European countries. This peculiarity is caused by the specificity of
Russian cause-of-death coding practice, which results in underestimating the
mortality from certain causes at old ages.
PMID- 28509474
TI - [The season of birth and mortality (Based on workers mortality epidemiological
study materials)].
AB - The article presents a comparative assessment of the death absolute risk for the
humans born in different seasons and months of the year based on the
epidemiological studies found on the retrospective cohort for the 40 years period
(the end of the 20th-beginning 21st century). It is shown that mortality of
people born in January-February differ from similar parameters of persons born in
March-April.
PMID- 28509475
TI - [About expedience and perspectives of immortalism].
AB - The human environment is subjected to changes due to anthropogenic activity. It
will change in future as well. To survive, the human population should
genetically be reorganized according to these changes. This requires an
alternation of generations. The mechanism of senescence is not atavism from which
we should escape but the achievement of evolution without which the humanity
cannot exist.
PMID- 28509476
TI - [Temporal order deterioration and circadian disruption with age. 2. Systemic
mechanisms and correction].
AB - Part 2 of the present review highlights the impact of aging on mechanisms
involved in response of the circadian system to different photic and non-photic
factors, especially zeitgebers. Promising strategies to prevent age-dependent
circadian disruption using internal and external factors that may entrain
circadian rhythms are presented. In particular, benefits of bright light,
melatonin and other chronobiotics, the circadian body temperature rhythm,
physical activity and regular feeding schedules to preserve the temporal order of
aged organisms are discussed, emphasizing especially a personalized approach
based on the assessment of individual overt rhythms parameters.
PMID- 28509477
TI - [Neurocomputer identification of order parameters in gerontology].
AB - Investigation of distinctions discovered between three groups of different age
female-khanty (indigenous population of Ugra, Russia) of five active components
(from all 14 components registered) of a state vector of cardiovascular system
shows the wrong solving binary classification problem in a five dimensional phase
space by one iteration or a few iterations p (p<=50) using a neuroemulator. We
prove that solving binary classification problem by a neuroemulator must be
repeated about 1 000 times since it provides identifying more significant
diagnostic signs xi between two significant figures after comma which exhibit the
significance in diagnostics of aging rate (this is system synthesis problem
solving in gerontology).
PMID- 28509478
TI - [Telomere length, telomerase activity, stress and aging].
AB - The review is dedicated to analysis of data available at present time concerning
possible influence of stress upon telomere lengths and telomerase activity, as
well as various ways of counteracting it. Present-day telomerase theory of aging
gains a new impetus, shedding light upon the influence of psychological state of
humans and their ability to counteract stress, upon the process of aging. It also
tends to regard telomere shortening and the decrease in the activity of
telomerase as a marker of level of the ability to adapt to both inner and outer
influences. Both aging and age-dependent diseases are proved to be substantially
retarded not only by the administration of drugs, but also by psychological
means, which forms a good way towards healthy longevity. With complete
understanding of the impossibility to prevent or even to slow down natural
senescence itself, these methods allow to remove causes, which accelerate
senescence, and to increase the average human longevity.
PMID- 28509479
TI - [Study of gene expression of transcription factors T cells during aging].
AB - The level of expression of transcription factor genes (GATA-3, TBX21, IL23A), and
changing of oxidative modification of proteins in young and elderly healthy
persons was studied. The results of evaluation of gene expression, GATA-3 in
lymphocytes showed the increased expression of GATA-3 in elderly people in
comparison with the young. Women demonstrated higher expression of GATA-3 in
compare with men. Study of IL-2p showed reduced levels of expression in aged
humans compared to young. TVH21 expression level showed a reduction expression in
both men and women. Comparative analysis of protein oxidation in blood plasma of
young and elderly people showed an increase in the intensity of oxidative
modification of proteins in the elderly.
PMID- 28509480
TI - [Signal molecules of endometrium: gerontological and general pathhological
aspects].
AB - The review describes neuro-immuno-endocrine signal molecules expression in human
endometrial cells in the normal conditions, in the pathology and during aging.
Human endometrial cells synthesizes estrogen, progesterone, estradiol, progestin,
cell adhesion molecules (integrines alpha1beta1, alpha4beta1, alphaVbeta3, L
selectin, E-catgerin, MUC1), grow factors (TGF, EGF, HB-EGF, IGF), cytokines (IL
1, IL-2, INF-alpha, IL-12, SXSL10, CXCL11, CXCR3), various immune cells markers
(CD68, CD105, CD163, CD16, CD56, CD4, CD8), heat shock proteins (HSP60, HSP70,
HSP90, VEGF, MMP). Changes of this molecules expression level are the base of the
social significant diseases as endometriosis, endometrial cancer and infertility.
Thus, the investigation of neuro-immuno-endocrine interactions in endometrial
cells can be used for new drugs creating, in differential diagnostics of
endometrial cancer and increasing of extracorporal fertilization success.
PMID- 28509481
TI - [The type of age-related cataract as available marker of socially significant
diseases of the organism].
AB - The aim of the research was to investigate the general somatic status and to
investigate the influence of dominating part of vegetative nervous system,
following the different types of senile cataract formation in human. Thus, the
domination a sympathetic nervous system and correlated systemic dystrophic
changes of the tissues in patients with cortical cataract have been found for the
first time. Moreover, patients with nuclear cataract had the domination of
parasympathetic nervous system and another character of dystrophic changes.
Therefore, the type of a forming age-related cataract can be offered as an
available clinical marker of character of neurodystrophic process occurring in an
organism.
PMID- 28509482
TI - [Age-related changes in blood microcirculation functional state of the brain
cortex of rats].
AB - Male Wistar-Kyoto rats, aged 22-24 months, were intracerebrally transplanted
syngeneic mesenchymal stem cells (MSC). Cognitive functions of these animals were
tested in 3 weeks. The density of microvascular bed, the tissue blood flow,
saturation of mixed blood in cortex microvessels were measured under the standard
conditions, under the impact of noradrenaline and in the context of global
ischemia. The control groups consisted of rats aged 2-3 months and 22-24 months.
MSC transplantation have a positive impact on the microcirculation in brain
cortex of old animals: reduction of vascular density was prevented, level of
saturation in the blood vessels was increased, which enabled animals to endure
easier extreme impacts, but did not correct age-related deterioration of
cognitive functions.
PMID- 28509483
TI - [The influence of hyperhomocysteinemia on monoaminoergic systems of hypothalamus
and hippocampus of female rats at aging].
AB - The data presented have shown the different effect of hyperhomocysteinemia
(induced by 0,12-0,15 mg of methionine loading per os during 30 days) on
monoamines content in hypothalamus and hippocampus of young (6-7 month) and old
(20-22 month) female rats. It has been established that the level of
catecholamines (noradrenaline, dopamine), 5 oxitryptamine and 5 oxyindolacetic
acid in hypothalamic areas responsible for synthesis and secretion of
gonadoliberin (medial preoptic area and medial eminence with arcuate nuclei) is
considerable less in old animals compared with young ones. These data are in
agreement with the low content of gonadoliberin found by us in medial eminence
with arcuate nuclei. It has been also shown the decreased level of monoamines
level in hippocampus of old rats, which does not depend on methionine loading.
However in hippocampus of young animals hyperhomocysteinemia induced a noticeable
reduction of noradrenaline and 5 oxyindolacetic acid, which can lead to weakening
of animal's cognitive function.
PMID- 28509484
TI - [Neuropsychological changes in cognitive function during the transition of the
elderly in old].
AB - The goal is to track changes in psychophysiological characteristics of cognitive
functions associated with the transition of the elderly in the senile. 46 elderly
people with a mean age of 70,5+/-1,7 years were surveyed. After 7 years remaining
25 people were re-examined. The method of time estimation of right - and left
brain reactions to various stimuli - visual, auditory, and cutaneous signals at
rest and on the background of mental stress was applied. In non-survived subjects
in the initial survey the indicators of right- and left-brain reactions were
delayed, further slowing in response to mental stress, while survivors' reactions
of both hemispheres were very active, and the mental load caused activation of
both hemispheres. Re-examination of survivors conducted after 7 years has
revealed they slow right- and left-brain reactions, while the mental load caused
them already noticeable inhibition of the left hemisphere. Identified in the
study positive correlation of cognitive resource in old age with survival of the
individual to the senile age should be regarded as a manifestation of the
physiological relationship of integrative properties of the brain and organism
viability in ontogenesis. In this regard, the state of reactivity of the sensory
areas of the brain can be considered as one of the indicators of the prognosis of
survival of a person under a certain age.
PMID- 28509485
TI - [Clinical and pathogenetic features of ischemic stroke among representatives of
different gender and age].
AB - We observed 1410 patients of different gender and age with ischemic stroke of 4
main clinical and pathogenic types - atherothrombotic, cardioembolic, hemodynamic
and lacunar. The dependence of the pathogenic type of stroke, background options
for stroke pathology and risk factors of stroke on sex and age of patients was
analyzed. We founded out that atherothrombotic ischemic stroke is more common for
persons of retirement age, and in working paeople - gap and hemodynamic once,
although atherothrombotic strokes in this age group were more frequently observed
among men. The importance of hypertension in the development of ischemic stroke
reduces with age, but the role of cerebral atherosclerosis, ischemic heart
disease and cardiac arrhythmias increases. As risk factors for ischemic stroke in
the pension age physical inactivity, overweight and dyslipidemia play the main
role, when reducing the role of smoking and stress, more relevant for working
people. The frequency of the presence of certain risk factors and background for
ischemic stroke disease depends on the patient's gender, but in different age
periods and under different pathogenic types of ischemic stroke this dependence
changes and in people of retired age it is less distinct than in working people.
PMID- 28509486
TI - [Early diagnosing of delirium in the elderly with acute stroke].
AB - Delirium is a common complication of stroke worsening its prognosis. The aim of
the work is to identify the group of risk for the development of delirium among
elderly patients with acute stroke and assessment of diagnostic value of 4-A test
in identifying delirium in this category of patients. We included 73 patients in
the study, 33 (45 %) of which had symptoms of delirium according to DSM-IV.
Patients with delirium had more severe neurological deficit, more prominent
chronic changes on brain CT, more often had positive axial reflexes, had higher
erythrocyte sedimentation rate. All patients with pneumonia were delirious.
Russian version of 4-A test showed good psychometric properties. Thus the risk of
the development of delirium in older adults with acute stroke is higher among
patients with severe strokes, more prominent chronic changes in the brain
according to CT and clinical examination and in those with inflammatory
complications. Purposeful screening of the patients with aforementioned risk
factors with instruments such as 4-AT will allow more efficient and fast
diagnosing of delirium on early stages in the elderly with acute stroke.
PMID- 28509487
TI - [Evaluation of pharmacotherapy with perindopril, lozartan potassium and its
combination in elderly patients with chronic heart failure].
AB - To assess the pharmacotherapy of elderly patients with chronic heart failure
(CHF), by studying the effect of perindopril, lozartan potassium and their
combination on the severity of clinical symptoms, hemodynamics, exercise capacity
and heart morphofunctional parameters, 78 patients with chronic heart failure II
IV FC (for classification NYHA), complicating the course of coronary heart
disease (CHD) with left ventricular ejection fraction <=45 % were examined. Men
were 42 (53,8 %), women - 36 (46,2 %), mean age 64,8+/-3,7 years. The study
revealed that the background as long-term monotherapy with perindopril and
lozartan potassium in patients with CHF complicating CHD, CHF FC decreased
significantly and significantly increased left ventricular ejection fraction (p <
0,05). The combined treatment with perindopril and lozartan potassium showed no
advantage over monotherapy with these agents. These patients showed a decrease in
the frequency of angina attacks by 28,5 and 27 % respectively (p < 0,05) only
after a long course of treatment with perindopril and the combination of
perindopril and lozartan potassium.
PMID- 28509488
TI - [Metformin reduces the signs of sarcopenia in old OXYS rats].
AB - The increasing prevalence of sarcopenia (with the gradually aging population)
necessitates the development of effective prophylactic strategies. As promising
geroprotectors that comprehensively influence the processes of aging, mimetics of
caloric restriction are being actively studied, for example, the antidiabetic
agent biguanide Metformin (MF). We tested the influence of MF on the signs of
sarcopenia in senescence-accelerated OXYS rats during oral administration (100 or
300 mg per kilogram of body weight per day, with feed) from age 19 to 24 months:
the period when the signs of sarcopenia are present. We analyzed the effects of
MF on muscular strength of the rats and on structural and functional parameters
of skeletal muscle by means of light microscopy. MF slowed down the age-related
atrophy of muscle fiber bundles because it slowed the necrosis of some fibers,
sclerotic changes in skeletal muscle, and hypertrophy of connective tissue of the
perimysium (with a greater effect on the endomysium). MF also substantially
improved the blood supply and metabolism in the fibers. As a result of MF
treatment, the structure of skeletal muscle of OXYS rats approached that of
Wistar rats (healthy control) in terms of qualitative and quantitative
parameters; this improvement increased the muscle strength of OXYS rats and
abrogated the weight loss that is characteristic of old age.
PMID- 28509489
TI - [Assessment of work ability index in evaluation of small peptides geroprotective
effect].
AB - We have conducted a comparative analysis of the work ability index (WAI)
application in evaluation of the effectiveness of small peptides (cytogens) used
as geroprotectors in the system of preventive medical nutrition of those working
with occupational hazards. Our study revealed the necessity of an inclusion of
small peptides into the system of preventive medical nutrition, health promotion
in people working with occupational hazards and thus subjected to an accelerated
aging. The combined application of peptide geroprotectors makes it possible to
restore and enhance adaptive resources as well as to correct work ability and
maintain health and well-being in different professional groups.
PMID- 28509491
TI - [Increase of drainage and immune functions of the lymph node as a factor of
endoecological well-being in elderly and senile age].
AB - Age-related changes in mesocolic lymph node reflect the general process of
ageing. In lymph node, these changes are associated with size reduction of
structural and functional areas in the setting of manganese excess and iron,
zinc, and selenium deficiency, which determines the reduction of lymphoid tissue
functional activity in elderly and senile ages. We have realized the idea to
control the lymphatic system functions using phytotherapy. Phytotherapy provides
improving drainage, detoxication, and immune function of the lymph node by
increasing the size of functional compartments, intensification of
lymphoproliferative processes and mitigating the deficiency of the main trace
elements. The identified lypmhotropic effects of phytotherapy are interconnected
with endoecological well-being factor and the increase of nonspecific body
resistance in late ontogenesis. This result is of practical importance for the
optimization of endoecological rehabilitation.
PMID- 28509490
TI - [Postural control characteristics in elderly women with fallers].
AB - Using computer posturografic (stabilometric) complex a study of postural control
peculiarities was carried out in 108 women aged 65-74 years who had experienced
two or more falls during the year (fallers). These tests were: Sensory
Organization Test, Motor Control Test, Rhythmic Weight Shift. It was found that
elderly women with fallers had a decrease of sensory information (somatosensory -
by 1,8 %, of the visual - by 6 %, and of the vestibular - by 10,1 %), the
neurophysiological mechanisms of postural control (by 5,7 points), violation of
adaptation possibilities of sensory and motor components of the legs to respond
quickly to changes in the center of gravity within the support base of its
footing (7,3 ms), as well as reducing balance control in the frontal (by 7,2 %)
and sagittal (by 23,2 % ) planes compared with the women of the same age without
fallers.
PMID- 28509492
TI - [Suitable working conditions for elderly people with different degrees of
compensation of dysfunctional blood circulation of eyes].
AB - In dealing with complex problems in labor and social rehabilitation of elderly
people with different degrees of compensation of dysfunctional blood circulation
of eyes, a great role play methods of rational and qualitative analysis of
appropriate employment. The analysis of 110 patients of 55-70 years of age (220
eyes) with dysfunctional blood circulation of eyes has been done. Professional
abilities of elderly patients with dysfunctional blood circulation of eyes depend
on the state of functioning vision and the level of blood circulation of the eye.
In our study we show the clinical and prognostic data and based on that we could
develop the absolutely prohibited working conditions depending on the level
dysfunctional blood circulation of eyes of elderly people.
PMID- 28509494
TI - [Influence of age and degree of compensation of carbohydrate metabolism on
metabolic changes in blood of women patients with type 2 diabetes].
AB - The purpose of this study was a comprehensive analysis of various aspects of
metabolism of erythrocytes in women with type 2 diabetes, according to the age
characteristics of compensation of carbohydrate metabolism. The obtained results,
based on the nature of changes in parameters of carbohydrate and energy
metabolism, gas transport and antioxidant systems of blood, contribute to the
understanding of the role of metabolic changes in red blood cells, leading to
changes in their biological properties, severity of which reflects the adaptive
capacity of the organism in terms of hyperglycemia in different age groups in
type 2 diabetes.
PMID- 28509493
TI - [Pinealon and Cortexin influence on behavior and neurochemical processes in 18
month aged rats within hypoxia and hypothermia].
AB - The research of Cortexin and Pinealon within two models of stress, acute
hypobaric hypoxia and mild hypothermia, within 18-month aged rats has been held.
The peculiarities of peptide preparations' influence on behavior and
neurochemical indeces have been identified. Cortexin shows a more pronounced
effect on free radical processes and caspase 3 activity in brain than Pinealon.
Both preparations forward an accumulation of adrenergic mediator within rats'
brains in the model of acute hypobaric hypoxia, as well as serotonin within
cerebrum cortex in the model of mild hypothermia, which may underlie their
geroprotective effects.
PMID- 28509495
TI - [Metabolic syndrome and cognitive impairment in aging patients with
dyscirculatory encephalopathy].
AB - The relationship between metabolic syndrome and its individual components, leptin
levels and the severity of cognitive impairment in patients of different age with
dyscirculatory encephalopathy (DE) and metabolic syndrome (MS) was studied. There
were 503 patients aged 45-89 years with DE enrolled into the study, who were
divided into two groups: patients without MS (n=198) and with MS (n=305). All
patients were divided into three age subgroups. All patients underwent clinical
neurological examination, laboratory tests, high resolution B-mode ultrasound
examination, MRI. Cognitive functions were assessed by Mini Mental State
Examination (MMSE). In middle age and elderly patients a significant inverse
relationship between the total score of MMSE and the level of blood pressure,
blood glucose level was found. A direct significant correlation between blood
pressure level and a total score of MMSE was revealed in senile patients. The
duration of hypertension significantly influenced on the severity of cognitive
impairment in patients of middle and old age. The results obtained indicate a
definite relationship between the level of leptin in the blood of patients with
MS and the state of their cognitive functions. The influence of leptin level on
cognitive function in patients with the metabolic syndrome increases with age.
Timely and adequate correction of blood pressure, blood glucose and triglycerides
may have a positive effect on cognitive function in patients with MS.
PMID- 28509496
TI - [Ways of life quality improvement among elderly and older patients after
phacoemulsification of cataract in postoperative period].
AB - The article is devoted to the literature review of modern methods of diagnosis
and surgical treatment of age-related cataract. The comparative analysis of
morphologic characteristics of corneal endothelial cell before and after
phacoemulsification in the age aspect has been given. The results of surgical
treatment of this disease have been analyzed. The methods of prevention and
therapy of the postoperative complications have been described. Drug
administration scheme in the postoperative period is presented. The influence of
peptides on the cellular immunity indices and stimulation of regenerative
processes in eye's tissues in different diseases and pathological conditions
after surgical operation are considered. It has been given the estimation of the
ratio of visual function and quality of life in the elderly.
PMID- 28509497
TI - [Metabolic risk factors in patients 60 years and older with arterial
hypertension, living in extreme conditions of the Far North].
AB - To evaluate the criteria of metabolic syndrome (MS) in elderly, 505 men aged 60
99 years, with hypertension, indigenous and non-indigenous ethnic group living in
the extreme conditions of the Far North were studied. The analysis of
anthropometric parameters revealed that height, body weight, BMI, waist
circumference, hip circumference, the ratio of waist to hip size, waist to growth
were significantly lower in the elderly and senile Yakuts compared with those of
non-indigenous ethnicity (p<0,001). Ethnic differences were found in SBP and DBP
levels (p<0,001). The obtained results suggest that in elderly, old age patients
and centenarians living in the Far North, almost all analyzed parameters of the
metabolic syndrome were significantly correlated with abdominal obesity
(p<0,001).
PMID- 28509498
TI - [Prevalence of stomalgy and its causes in people of different age].
AB - On the basis of analysis of primary medical records of 9 158 (3 329 males and 5
829 females) patients of average, elderly and old age of outpatient clinics the
prevalence of pain and paresthesys of the oral mucosa and tongue was studied.
Profile of outpatient medical institutions, where people suffering from painful
phenomena and paresthesys of the oral mucosa pass examination and treatment was
defined. The causal factors that play a role in the origin and development of
this disease in patients of older age groups were established.
PMID- 28509499
TI - [Influence of gerodietetic meat pate on metabolic parameters in the elderly: the
role of vitamin B12].
AB - Many studies indicate essential nature of food in maintaining health. An
important factor is the consumption of a variety of essential elements, in
particular vitamins. The aim was to determine the relationship of vitamin B12
levels in serum with metabolic parameters and the possibility of correction using
gerodietetic meat pate. A total of 23 older people (60-80 years) were surveyed.
We determined index mass body, waist circumference, biochemical indicators,
vitamin B12 concentration in serum and food consumption (by frequency method). We
also measured changes in these parameters under the influence of eating
gerodietetic meat pate. The older adults often demonstrate deficient in vitamin
B12 in the blood (about 65 % of the surveyed), which may be contributed both by
its lack of dietary intake and malabsorption due to pathological changes in the
digestive system. The content of vitamin B12 in the blood of the elderly has been
closely linked to metabolic indicators and body mass. Using gerodietetic meat
pate promoted not only the elimination of vitamin B12 deficiency, but also
significantly improved the biochemical markers of protein, and especially lipid
metabolism in the elderly (decreased low-density lipoprotein and high density
lipoprotein increased).
PMID- 28509500
TI - [Correction of impaired glucose tolerance using tetrapeptide (Pancragen) in old
female rhesus monkeys].
AB - The aim of the investigation was comparative study of the influence tetrapeptide
Pancragen (St. Petersburg Institute of Bioregulation and Gerontology, St.
Petersburg) on hormonal function of the pancreas compared to the effect of widely
used hypoglycemic drug - glimepiride. The investigation involved 9 old (20-25
years) clinically healthy rhesus monkey females (Macaca mulatta). Five of them
were injected with Pancragen (0,05 mg/animal per day during 10 days,
intramuscularly) for 10 days; 4 animals received glimepiride (4 mg/animal per day
during 10 days, per os). Blood samples were taken from all the animals with
subsequent analysis of glucose, insulin and C peptide levels; the manipulation
was performed before administration of the drugs, on the background of their
administration and after their withdrawal in basal conditions, as well as during
glucose tolerance testing. Pancragen and glimepiride administration induced the
decrease of blood glucose basal levels in both groups of old monkeys. Pancragen
also normalized insulin and C peptide levels suggesting its recovering effect on
the disturbed tolerance to glucose in old animals. At the same time, glimepiride
administration led to a more expressed and delayed hypoglycemic effect and C
peptide secretion stimulation without any significant effect on insulin
secretion. The data suggest that Pancragen is effective and safe for correction
of age-related imbalance of endocrine pancreatic function, and can be used for
elderly patient with disturbed glucose tolerance.
PMID- 28509501
TI - [The quality of life of elderly citizens in Kazakhstan (by the example of
Astana)].
AB - The article presents the results of the study of self-assessment of quality of
life of older Kazakhstan citizens. The differences between the self-assessment of
quality of life of older people living in institutional care in the hospital and
outside the hospital are discussed. The results show that elderly people who live
in institutional care in a hospital, assess the quality of life is better than
older people living independently.
PMID- 28509502
TI - [Preventive geriatrics vs anti-aging medicine].
AB - The article presents the main modern ideas of the new interdisciplinary direction
at the junction of aesthetic medicine, geriatrics and valeology - preventive
geriatrics, or the anti-aging medicine. Describes its purpose, namely effective
individual programs of prevention of the development and progression of chronic
diseases and age-related conditions; the overview of the diagnostic methods used
in preventive geriatrics, individualized prevention programs with proven efficacy
is given. Substantiates the importance of preventive geriatrics (anti-aging
medicine) as a discipline with its own scientific methodological tools, points of
application, and presents prospects of scientific study.
PMID- 28509503
TI - 'Own-Label' Versus Branded Commercial Dental Resin Composite Materials:
Mechanical And Physical Property Comparisons.
AB - A majority of dental materials are manufactured by companies who have experience
in the field. However, a number of "own label" materials have become available,
principally marketed by distributors and other companies with little or no
experience in the field. These materials are attractive because of their reduced
cost, but they may have no research on which clinicians might base their
potential performance. It is therefore the purpose of this work to compare the
performance of different batches of a number of "own-label" dental materials with
a similar number from manufacturers with experience in the field, using a variety
of laboratory test regimes which include filler determination, degree of
conversion, flexural strength and flexural modulus, in order to evaluate key
material properties. The results indicated that own-label dental resin composites
produced similar results to materials from established companies in terms of
flexural strength characteristics and degree of conversion. However, a greater
batch-to-batch variation in several mechanical and physical properties of the own
label materials was noted.
PMID- 28509504
TI - Marginal Adaptation, Gap Width, and Fracture Strength of Teeth Restored With
Different All-Ceramic Vs Metal Ceramic Crown Systems: An in Vitro Study.
AB - This study evaluated marginal adaptation before and after thermomechanical (TCML)
loading, gap width and fracture strength of all-ceramic single crowns, as
compared to porcelain-fused-to-metal (PFM). Thirty extracted premolars were
prepared with a round shoulder of 1.0 mm depth. Specimens were restored with
zirconia-ceramic (Group 1), lithium disilicate (Group 2) and metal-ceramic single
crowns (Group 3). The replica of each sample was observed with a scanning
electron microscope (SEM) to evaluate the crown-cement (c-c) and tooth-cement
interface (t-c). After TCML, perfect margins decreased to 91.3% (c-c) and 93.9%
(t-c) in Group 1, 94.6% (c-c) and 96.0% (t-c) in Group 2 and 73.5% (c-c) and
53.1% (t-c) in Group 3. The mean fracture strengths were 654.8 +/- 98.1 N for
Group 1, 551.3 +/- 127 N for Group 2 and 501.43 +/- 110.1 N for Group 3. All
ceramic systems could substitute for metal-ceramic crowns, but chipping of
veneering ceramics, especially in zirconia-based crowns, should be investigated.
PMID- 28509505
TI - Effects of Different Porcelains and Shades on Light Transmission and Resin
Polymerization.
AB - This study evaluated the effect of light-curing through two ceramics on the
degree of conversion-(DC) and Knoop microhardness-(KHN) of resin cements. Three
shades were used and light-cured directly on a Golden Gate attenuated total
reflectance FT-IR plate at 30 degrees C. KHN was tested immediately and after 24
h. Resin shade, type of ceramic, and storage time all had significant effects on
the DC and KHN values. Within each shade, the choice of ceramic always had a
significant effect, but the shade of the resin had a greater effect. There was an
increase in KHN of all cements after 24-h of storage.
PMID- 28509506
TI - Anti-Inflammatory and Regenerative Effects of Albanian Propolis in Experimental
Vital Amputations.
AB - This study evaluated the effects of Albanian propolis on the inflamed pulpal
tissue after pulpotomy in piglets. In five piglets, two teeth each were infected
using special pathogenic microbial flora that was prepared in advance in order to
cause inflammation of the pulp. Pulpotomy was performed in the maxillary and
mandibular central and lateral incisors. Microbial flora pathogenesis prepared
from the section of infected teeth, containing Staphylococcus aureus,
Streptococcus viridans, Enterococcus faecalis, Staphylococcus albus and mixed
flora were used to cause artificial pulpitis. The first group consisted of
piglets with the teeth having pulpal inflammation and regeneration without
medication served as the control group. In the second group, the teeth were
treated with pure propolis after vital amputation. In the 3rd, 4th and 5th
groups, the teeth were treated after vital amputation with the compounds of
ZnO+10%, ZnO+20% propolis in ethanol, and with the paste composed of Ca(OH) +30%
oily propolis, respectively. In half of the teeth, propolis based pastes were
applied on the pulp and entries of the cavities were isolated with glass ionomer
cement while the other half did not receive this treatment and acted as the
control. The cavity entries were obturated with chemically polymerized resin
composite. Inflammatory response, dominated by polymorphonuclear cells, was
observed in the dental pulpal tissue of all the teeth that were not treated with
propolis-based paste. Radiography and histopathology analyses were performed to
survey the infected pulp tissue treated with propolis up to 3 months. Data were
analyzed using Mann-Whitney U test (a=0.05). After vital amputation of the pulp,
application of Albanian propolis showed significantly higher anti-inflammatory
and regenerative effect creating dentin barrier after 3 months of treatment
compared to control group (p?0.05). These results were more expressed in the
group containing 20% propolis in ethanol+ZnO.
PMID- 28509508
TI - A Survey on Prevalence, Causes and Prevention of Postcementation
Hypersensitivity.
AB - This study evaluated the prevalence and causes of post-cementation sensitivity
and possible prevention measures according to the experience of dentists through
an internet survey. A questionnaire was prepared with 25 items based on a survey
introduced by Rosenstiel and Rashid. An online site was created for the
participation to the survey. A total of 322 participants responded the
questionnaire. The results of the questionnaire indicated the amount of tooth
preparation (42.1%) is the most frequent reason for hypersensitivity followed by
water-cooling with pressure (11.2%) and provisionals (10.9%). "Very important"
response for tooth reduction, time before cementation, overheating, luting agent,
occlusion and provisionals were found to be of statistical significance
(p?0.001). Comparing respondents' opinions the incidence of post-cementation
sensitivity appears to be underestimated. Tooth reduction, preparation under high
volume spray and quality of provisional restorations was considered to have a
significant impact on the incidence of post-cementation sensitivity according to
the dentists surveyed across Turkey. Respondents to the questionnaire considered
the use of antimicrobial, desensitizing, resin bonding, hemostatic agents,
varnishes, type of liner material, rotary instruments to be less effective for
prevention of post-cementation sensitivity.
PMID- 28509507
TI - A Practice-Based Clinical Evaluation of a Bulk Fill Restorative Material.
AB - OBJECTIVE: To evaluate the handling, by a group of practice-based researchers, of
a recently introduced bulk fill resin-based composite restorative material,
Filtek Bulk Fill Restorative (3M ESPE). METHODS: The twelve selected evaluators
were sent explanatory letters, a pack of the material under investigation to use
for 8 weeks, and a questionnaire. RESULTS: The evaluators rated the ease of use
of the bulk fill restorative the same as the previously used posterior composite
material. The provision of one shade only for evaluation may have compromised the
score for aesthetic quality. No post-operative sensitivity was reported.
CONCLUSIONS: The bulk fill material was well received as indicated by the high
number of evaluators who would both purchase the material and recommend it to
colleagues. CLINICAL REVELANCE: A recently introduced bulk fill restorative
material achieved a rating for handling which was similar to the evaluators'
previously used resin composite, although there were some concerns regarding the
translucency of the material.
PMID- 28509509
TI - Fracture of Zirconia Abutment with Metallic Insertion on Anterior Single Titanium
Implant with Internal Hexagon: Retrieval Analysis of a Failure.
AB - This case report presents a retrieval analysis of a screw-retained one-piece
restoration with the veneering ceramic fired directly onto the zirconia abutment
that fractured during insertion. A patient who experienced root fracture of a
maxillary left central incisor received a titanium implant on the same day as
extraction. After delayed implant loading, a two-piece zirconia abutment with
metallic insertion was customized. Upon installation, a horizontal fracture of
the crown just above the metallic portion was detected. The retrieval analysis of
a fractured zirconia abutment showed crack formation and diffusion of glaze
material that expanded the crack line during firing.
PMID- 28509510
TI - Editorial: Selling a sugar tax: the sweet smell of success?
AB - This editorial briefly considers the increasing epidemic of obesity and Type 2
diabetes, the underlying drivers of junk food and sugary drinks, and the recent
scientific and campaigning movements culminating in the UK Chancellor's surprise
announcement of a Sugary Drinks Levy.
PMID- 28509511
TI - The teaching of Dental Public Health - 50 years on.
AB - In 1966, James published an article in the British Dental Journal (and reprinted
here) which made recommendations on the teaching of dental public health. The
following commentary reviews the ideas put forward by James and how these relate
to concepts of dental public health in the undergraduate dental curricula of 2016
.
PMID- 28509512
TI - The teaching of Dental Public Health and its relation to Children's Dentistry.
PMID- 28509513
TI - Challenges identified in a pilot outreach dental service for Traveller children
in Hackney, East London.
AB - Impetus for action: Inequity of dental health and dental service use for
Travellers in the UK. National guidance on improving community oral health,
stresses an imperative to involve and engage with "those whose economic, social
and environmental circumstances or lifestyle place them at high risk of poor oral
health or make it difficult for them to access dental services". Solution: Oral
health promotion and simple treatments were provided on two Traveller sites from
a mobile dental unit (MDU) over a 5-day period and patients with extensive oral
disease were referred to a fixed-site clinic for continued care. Outcomes: Most
children, 60%, reportedly brushed once daily or less, only 40% brushed twice
daily. Obvious visual caries were evident in 23 out of the 35 children (66%). A
moderate to high risk of developing future caries was identified in 92% of
Traveller children based on their existing diet, oral hygiene practices and
caries experience. Future: Oral care was successfully provided on an MDU, but
this is an expensive resource and should not be considered a permanent solution.
Oral health promotion messages delivered in the families' homes or local
community settings through their established health services, such as health
visitors or community nurses, may help to reinforce good oral hygiene and diet
practices and needs robust evaluation.
PMID- 28509514
TI - Lay public's use of a support group for general dental problems.
AB - OBJECTIVE: To categorize and tabulate layperson inquiries made to an Internet
dental health support site to identify oral conditions and associated behaviors
of concern. METHODS: A retrospective tabulation of wall postings was made from an
established dental health support website hosted by WebMD over a 2-year period
(April 2013-April 2015). A mixed method approach of content and thematic analysis
was used. Content analysis identified content of oral health concerns, while
thematic analysis using grounded theory identified themes and beliefs concerning
associated behaviors. RESULTS: The presence of non-descript growths on the tongue
and swelling and/or discoloration of the lips elicited the most inquires. These
were often self-diagnosed as oral candidiasis, a STD or a carcinoma, provoking
high levels of self-concern. Unprotected sexual activity, excessive ingestion of
soft and hard beverages, smoking and overexposure to the sun were the most
frequently self-reported behaviors associated with their concerns. Many questions
focused upon "normal" healing, including the amount of edema and discomfort that
could occur following oral surgery or other dental procedures. Information
concerning alternative treatments was often solicited, and many alluded that they
had not been provided sufficient information to make informed decisions prior to
dental treatment. CONCLUSIONS: Laypersons have many oral health concerns
particularly in relationship to the development of undiagnosed pathologies in
conjunction with a history of volitional behaviors. The dental community should
monitor these sites to provide advice and links to information about common oral
health concerns and their possible association with detrimental behaviors.
PMID- 28509515
TI - Understanding avoidance and non-attendance among adolescents in dental care - an
integrative review.
AB - OBJECTIVE: To review articles exploring manifestations of avoidance of or non
attendance to dental care, to identify background and concomitant factors
specifically associated with dental avoidance among adolescents. METHODS: PubMed,
CINAHL and PsychINFO were searched using MeSH terms and keywords covering dental
avoidance, non-attendance and non-utilization. Searches were limited to peer
reviewed studies in English, published in 1994-2014. Twenty-one research articles
were included. Data were extracted, ordered, coded, categorized, and summarized
according to the integrative review method. RESULTS: The identified factors
formed three common major themes: Environmental, Individual and Situational
factors. Only seven studies, all from Sweden or Norway, investigated factors
associated with dental avoidance. The remaining 14 studies were geographically
widespread. Regarding avoidance, the main focus was found to be on individual and
situational factors, while environmental factors were more often investigated for
the outcome non-attendance. CONCLUSIONS: Although a wide variety of
environmental, individual and situational factors could be summarized in this
review, factors specifically associated with dental avoidance in a context of
free dental care still need to be investigated. The possible impacts of cultural
background, of tobacco, alcohol or drug use and of psycho-social circumstances
deserve further research. Clinical implications of today's knowledge may be to
pay attention to the adolescents' individual background and everyday life
situation, to offer agreed and individualized treatment, taking fears and
attitudes into consideration, to avoid painful treatments, and to be alert for
early signs of avoidance.
PMID- 28509516
TI - Variations in survival time for amalgam and resin composite restorations: a
population based cohort analysis.
AB - OBJECTIVE: To estimate the association between the restorative material used and
time to further treatment across population cohorts with universal coverage for
dental treatment. BASIC RESEARCH DESIGN: Cohort study of variation in survival
time for tooth restorations over time and by restoration material used based on
an Accelerated Failure Time model. CLINICAL SETTING: Primary dental care clinics.
PARTICIPANTS : Members of Canada's First Nations and Inuit population covered by
the Non-Insured Health Benefits program of Health Canada for the period April 1,
1999 to March 31, 2012. INTERVENTION : Tooth restorations using resin composite
or amalgam material. MAIN OUTCOME : Survival time of restoration to further
treatment. RESULTS : Median survival time for resin composite was 51 days longer
than amalgam, for restorations placed in 1999-2000. This difference was not
statistically significant (p?0.05). Median survival times were lower for females,
older subjects. Those visiting the dentist annually, and decreased monotonically
over time from 11.2 and 11.3 years for resin composite and amalgam restorations
respectively placed in 1999-2000 to 6.9 and 7.0 years for those placed in 2009
10. CONCLUSIONS : Resin composite restorations performed no better than amalgams
over the study period, but cost considerably more. With the combination of the
overall decrease in survival times for both resin composite and amalgam
restorations and the increase in use of resin composite, the costs of serving
Health Canada's Non-Insured Health Benefits population will rise considerably,
even without any increase in the incidence of caries.
PMID- 28509517
TI - Impact of providing free preventive dental products without health workers'
counselling on infants' tooth-brushing and bottle-feeding termination practices:
a randomised controlled trial.
AB - OBJECTIVE: To investigate the impact of an integrated oral health promotion
intervention, within the Syrian national immunisation programme, which provided
free preventive dental health products, without health workers' counselling, on
one-year-old infants' tooth-brushing and bottle-feeding termination practices.
RESEARCH DESIGN: a randomised controlled parallel-group trial. SETTING: A
maternal and child health centre in Sweida city, Syria. PARTICIPANTS : 92 mothers
of one-year-old infants, attending an infant vaccination clinic, were allocated
into three groups: Test, Control One and Control Two. INTERVENTIONS : The Test
group received an oral health promotion package including an infant oral health
pamphlet, a baby toothbrush, fluoride toothpaste (1,000 mg/L) and a trainer cup,
without health workers' counselling. Control One received only the pamphlet,
whilst Control Two received no intervention. MAIN OUTCOME MEASURES : after one
month, the presence of old plaque on infants' primary teeth was checked, to
assess tooth-brushing behaviour. Also, a mothers' self-completed questionnaire
was administered to assess bottle-feeding use. RESULTS : The response rate was
100% and the attrition rate was zero. There were differences in tooth-brushing
and bottle-feeding termination practices between the three groups (P?0.001).
Infants in the Test group were less likely to have old plaque and more likely to
stop bottle-feeding than their counterparts in the two control groups. There were
no differences in the abovementioned outcomes between the two control groups.
CONCLUSIONS : Providing free preventive dental health products, without health
worker's counselling, in an integrated oral health promotion intervention, was an
effective measure to promote infants' tooth-brushing and bottle-feeding
termination practices. These findings should be supported by long-term follow up
studies.
PMID- 28509518
TI - The dental public health implications of cosmetic dentistry: a scoping review of
the literature.
AB - INTRODUCTION: The popularity of cosmetic surgery has seen a rapid increase
recently, with the trend mirrored in dentistry. The Department of Health
expressed concerns about the potential for biological and psychosocial harm of
these cosmetic procedures. Furthermore, the dental public health implications
(DPH) of the growing uptake of cosmetic dental procedures have not been explored.
OBJECTIVES: Conduct a scoping review to explore the DPH implications of cosmetic
dentistry and identify gaps for future research. METHODS: A fivestage scoping
review was conducted of studies identified using the search terms cosmetic AND
dentistry. Data from the studies meeting the inclusion criteria were extracted,
collated and summarised into themes. RESULTS : Fifty-seven papers met the
inclusion criteria (11 cross-sectional studies, 10 literature reviews and 36
opinion pieces). The DPH implications were summarised into five emergent themes:
dento-legal and ethical, marketing, psychosocial, biological and workforce. These
themes revealed patients' increased expectations, expanding commercialisation of
the profession, psychological risks to vulnerable patients, the iatrogenic
consequences of invasive cosmetic dental procedures and workforce implications of
the current trends. CONCLUSIONS : The scoping review found that existing
literature on cosmetic dentistry is predominately anecdotal - professional
opinions and discussions. Despite this, our findings demonstrated workforce
training and governance implications due to increased demand for cosmetic
dentistry. Further empirical research is needed to understand the DPH
implications of the increasing demand and uptake of cosmetic dental procedures to
guide evidence-based policy to safeguard patients and improve the quality of
dental services.
PMID- 28509519
TI - Development of life story experience (LSE) scales for migrant dentists in
Australia: a sequential qualitative-quantitative study.
AB - INTRODUCTION: The integration of qualitative and quantitative approaches
introduces new avenues to bridge strengths, and address weaknesses of both
methods. OBJECTIVE: To develop measure(s) for migrant dentist experiences in
Australia through a mixed methods approach. METHODS: The sequential qualitative
quantitative design involved first the harvesting of data items from qualitative
study, followed by a national survey of migrant dentists in Australia. Statements
representing unique experiences in migrant dentists' life stories were deployed
the survey questionnaire, using a five-point Likert scale. Factor analysis was
used to examine component factors. RESULTS : Eighty-two statements from 51
participants were harvested from the qualitative analysis. A total of 1,022 of
1,977 migrant dentists (response rate 54.5%) returned completed questionnaires.
Factor analysis supported an initial eight-factor solution; further scale
development and reliability analysis led to five scales with a final list of 38
life story experience (LSE) items. Three scales were based on home country
events: health system and general lifestyle concerns (LSE1; 10 items), society
and culture (LSE4; 4 items) and career development (LSE5; 4 items). Two scales
included migrant experiences in Australia: appreciation towards Australian way of
life (LSE2; 13 items) and settlement concerns (LSE3; 7 items). CONCLUSION : The
five life story experience scales provided necessary conceptual clarity and
empirical grounding to explore migrant dentist experiences in Australia. Being
based on original migrant dentist narrations, these scales have the potential to
offer in-depth insights for policy makers and support future research on dentist
migration.
PMID- 28509520
TI - Dental pain and its determinants in an adult population in Tehran, Iran, Urban
HEART-2.
AB - OBJECTIVE: To assess the prevalence of dental pain in the past year among adults
in Tehran-Iran, and its determinants. BASIC RESEARCH DESIGN: Cross-sectional
population study. PARTICIPANTS: A sample of 20,322 adults (18-64 years old).
METHODS : A questionnaire survey was conducted across the 22 districts using the
multi-stage random sampling method. Data were analysed applying the complex
samples method. Multiple logistic regression analysis was used to adjust the
effects of other variables on the outcome variable as dental pain in the past
year. RESULTS : Overall, 19,645 individuals with a mean age of 39.9 (SD=12.5)
years responded. Dental pain in the past year was reported by about one sixth
(14%) of subjects and associated with being widowed/divorced (OR 1.45, 95%CI 1.07
1.97, p=0.016), married (OR 1.24, 95%CI 1.04-1.47, p=0.016), Azari minority (OR
1.2, 95%CI 1.05-1.37, p=0.009) and having dental visit in the past year (OR 2.6,
95%CI 2.29-2.95,p?0.001). Older subjects (OR 0.76, 95%CI 0.59-0.97, p= 0.029),
those with a high economic status (OR 0.84, 95%CI 0.72-0.98, p=0.03), good (OR
0.75, 95%CI 0.58-0.96, p=0.023) or moderate oral health behaviour (OR 0.79, 95%CI
0.62-0.99, p=0.042), and good self-perceived oral health (OR 0.52, 95%CI 0.45
0.61, pp?0.001) were less likely to report dental pain. CONCLUSIONS : Dental pain
in the past year was associated with being married/widowed, being a minority, and
visiting a dentist in the past year. Older subjects and those with a high socio
economic status, good/moderate oral health behaviour, and good self-perceived
oral health were less likely to report dental pain.
PMID- 28509521
TI - Dermatofibrosarcoma protuberans: when the age makes the difference.
AB - BACKGROUND: Dermatofibrosarcoma protuberans is a malignant tumor that affects
exclusively the skin. It is a low-grade malignant tumor of subcutaneous tissues,
characterized by a local recurrence but it seldom metastasizes. This study aimed
to evaluate the impact of different clinical parameters on disease free survival
and overall survival of dermatofibrosarcoma protuberans patients. METHODS: A
retrospective study of data including seventeen cases of dermatofibrosarcoma
protuberans (eleven male, six female) retrieved from the files of the Dermatology
Clinics of La Sapienza University, Rome. We evaluated three clinical parameters
(age, sex and anatomic site of the primary tumor) using the Kaplan-Meier product
and the Log-Rank Test. RESULTS: The results highlighted that patients with an age
<=49 years showed a median disease free survival of 36 months, while patients
with an age >=50 years of 4 months (P<0.0003). In addition, performing Rank
correlation, only the variable age (P<0.0001) reached the statistical
significance. Regarding overall survival, performing Rank-correlation only the
variable age reached the statistical significance (P=0.02). CONCLUSIONS: Our data
suggests that age has a statistically significant role on disease free survival
and overall survival of dermatofibrosarcoma protuberans patients.
PMID- 28509522
TI - Construction of a three-dimensional in-vitro skin model on polycaprolactone
fibers.
AB - BACKGROUND: The aim of this study was to observe the morphological
characteristics and the biological properties of human epidermal cells when
cultured at an air-liquid interface in polycaprolactone (PCL) fibers as a three
dimensional scaffold for tissue engineering. METHODS: In this study, the
melanocytes and keratinocytes were obtained from human scalp skin, seeded onto a
PCL film, and cocultured for 2 weeks to construct a three-dimensional (3D) skin
model. The cells were then characterized by hematoxylin and eosin staining, by
immunohistochemical staining with antibodies to cytokeratin 15 (CK15), Ki-67,
CD34, CD200 and HMB45 and by transmission electron microscopy. RESULTS:
Keratinocytes and melanocytes grew well in the co-culture system. Hematoxylin and
eosin staining revealed that the cells adhered to the PCL fiber scaffold well,
the keratinocyte layer became a multilayered concentric structure and the surface
became distinctly keratinized at the air-liquid interface. Immunohistochemical
analyses exhibited a scattered distribution of cells expressing CK15, CD34,
CD200, Ki-67 and/or HMB45. Transmission electron microscopy revealed that the
keratinocytes contained a number of keratin fibrils and membrane-coated granules.
CONCLUSIONS: The PCL scaffold has excellent adhesiveness and biocompatibility
with human epidermal cells, and is suitable for constructing 3D skin models for
tissue engineering in the future.
PMID- 28509523
TI - Skin diseases and tattoos: a five-year experience.
AB - BACKGROUND: Decorative tattooing as a body art form underwent an exponential
increase during the last two decades, particularly among teenagers and young
adults. Consequently, the number of reported adverse reactions after tattooing
has increased. The most frequent reported skin reactions to tattoo include
infectious (bacterial, viral, fungal) or inflammatory (allergic contact
dermatitis and granulomatous reaction) diseases. Moreover, tattoos can also
induce the development of typical skin lesions of pre-existing dermatoses, a
phenomenon known as isomorphism reactive or Koebner phenomenon, which commonly
occurs in patients with psoriasis, vitiligo, or lichen planus. METHODS: A
retrospective study analyzing records data of patients attending the Department
of Dermatology, University of Naples "Federico II" during 2011-2015 was
performed. All cases of tattoo-related or closely-located dermatitis were
selected. RESULTS: We observed 19 patients (mean age: 26.4 years old) showing
cutaneous conditions related to the practice of tattooing. Allergic contact
dermatitis was reported as the most common cutaneous disease linked to tattooing
(31.6%), followed by granulomatous reactions (26.3%). These data are consistent
with those already reported in the literature. CONCLUSIONS: Our results highlight
the need to develop detailed regulations regarding tattoos practice, used
materials, as well as execution procedures in order to limit the outbreak of
tattoo-related skin diseases.
PMID- 28509524
TI - Eradication of basal cell carcinoma of the head and neck using the surgical
excision with a new stained margin technique: a preliminary study.
AB - BACKGROUND: Basal cell carcinomas (BCCs) are common cutaneous neoplasms that
mainly affect fair-skinned subjects, in sun-exposed areas of the body. The
treatment of choice of BCCs is represented by surgical excision and different
techniques are available, in order to allow the complete eradication of the tumor
with the best cosmetic results. In this paper, we describe the surgical excision
with stained margin technique (SMET) and we report its efficacy for the treatment
of BCCs of the head and neck region. METHODS: We retrospectively studied 177 BCCs
of the head and neck region treated by SMET: a surgical technique in which each
specimen is cut vertically like a bread-loaf in multiple sections of 1 mm of
thickness, after marking peripheral margins. RESULTS: We observed an overall
recurrence rate of 4.5% after SMET (mean follow-up: 26 months), with higher rate
in aggressive subtypes (P=0.04). BCCs located in high-risk sites and those
previously undergone to other non-radical therapies required two or more
procedures (P=0.008 and P=0.002, respectively), while no correlation was observed
between the number of SMET procedures and recurrence rate. CONCLUSIONS: In our
experience, since low recurrence rate was obtained by SMET, we suggest that it
may be taken into consideration as surgical option for BCCs of the head and neck
region.
PMID- 28509526
TI - Paraoxonases and psoriasis: negative imbalance of anti--oxidant endogenous
mechanisms.
AB - BACKGROUNG: Numerous reports have shown that psoriasis patients are more exposed
to lipoprotein peroxidation and to a decrease in the activity of paraoxonase
(PON)1, an anti-oxidant and anti-inflammatory enzyme. Thus, it has been suggested
that malfunction of the anti-oxidant system and an increased production of
reactive oxygen species drive immune inflammatory events, that result in
progressive skin cell damage in patients with psoriasis. The PON protein family,
including PON1, PON2 and PON3, is one of the most important endogenous defense
mechanisms against oxidative stress. In the present study, we investigated PON
gene expression in psoriasis and in cutaneous oxidative stress. METHODS: The
study population included 10 patients affected by moderate-to-severe plaque
psoriasis and 15 healthy donors who have undergone to plastic surgery, were used
as control. Skin punch biopsies of lesional and non lesional psoriatic skin were
performed for analysis of PON2 and PON3 gene expression. In addition, oxidation
assays in ex vivo full-thickness healthy skin organ cultures were performed.
RESULTS: No significant differences were observed between PON2 and PON3 gene
expression in psoriatic lesional and non lesional skin compared with healthy
controls. H2O2 treatment induced a significant decrease of PON2 and PON3
expression in ex vivo full-thickness healthy skin organ cultures; conversely the
pre-treatment of samples with the anti-oxidant reagent N-acetyl-L-cysteine (NAC)
induced a significant increase. Interestingly, no significant alterations were
reported for PON2 and PON3 expression in ex vivo full-thickness healthy skin
organ cultures stimulated with IL-17. CONCLUSIONS: Taken together our findings
have revealed that a strong pro-oxidative activity is not effectively countered
by anti-oxidant endogenous mechanisms both in psoriatic skin and in ex vivo
experimental model.
PMID- 28509527
TI - Robotically assisted minimally invasive mitral valve surgery.
PMID- 28509528
TI - Synthesis of Water-Soluble Ag2S Quantum Dots with Fluorescence in the Second Near
Infrared Window for Turn-On Detection of Zn(II) and Cd(II).
AB - The second near-infrared window emission (1.0-1.7 MUm, NIR-II) has received
extensive attention with the advantages of negligible tissue scattering, reduced
autofluorescence, and less background noise. Here a novel analysis platform based
on quantum dots (QDs) for highly selective detection of Zn2+ and Cd2+ with an
enhanced NIR-II fluorescence is reported for the first time. We have developed a
facile two-step route to synthesize the water-soluble Ag2S QDs, constituting of a
green hydrothermal process and followed surface ligands exchange. Surface
passivation was proposed to be the mechanism for the enhanced fluorescence. The
added Zn2+ or Cd2+ could react with the surface thioglycollic acid to form Zn
thiol or Cd-thiol complex passivation shell, which restored surface defects and
suppressed nonradiative recombination pathway. The detection platform exhibited a
linear relationship between the ion concentrations and enhanced fluorescence and
had a detection limit as low as 760 nM for Zn2+ and 546 nM for Cd2+ at pH = 7.4.
Furthermore, the as-synthesized Ag2S QDs showed good robustness in real sample
matrix and were demonstrated to be able to detect exogenous Zn(II) in cells.
These properties suggest potential applications of detection of Zn2+ in biology
and Cd2+ in environment via the NIR-II fluorescent Ag2S QDs.
PMID- 28509529
TI - Orientation Control of Interfacial Magnetism at La0.67Sr0.33MnO3/SrTiO3
Interfaces.
AB - Understanding the magnetism at the interface between a ferromagnet and an
insulator is essential because the commonly posited magnetic "dead" layer close
to an interface can be problematic in magnetic tunnel junctions. Previously,
degradation of the magnetic interface was attributed to charge discontinuity
across the interface. Here, the interfacial magnetism was investigated using
three identically prepared La0.67Sr0.33MnO3 (LSMO) thin films grown on different
oriented SrTiO3 (STO) substrates by polarized neutron reflectometry. In all cases
the magnetization at the LSMO/STO interface is larger than the film bulk. We show
that the interfacial magnetization is largest across the LSMO/STO interfaces with
(001) and (111) orientations, which have the largest net charge discontinuities
across the interfaces. In contrast, the magnetization of LSMO/STO across the
(110) interface, the orientation with no net charge discontinuity, is the
smallest of the three orientations. We show that a magnetically degraded
interface is not intrinsic to LSMO/STO heterostructures. The approach to use
different crystallographic orientations provides a means to investigate the
influence of charge discontinuity on the interfacial magnetization.
PMID- 28509531
TI - Hierarchical Porous Structured SiO2/SnO2 Nanofibrous Membrane with Superb
Flexibility for Molecular Filtration.
AB - The separation and purification of chemical molecules from organic media under
harsh chemical environments are of vital importance in the fields of water
treatment, biomedical engineering, and organic recycling. Herein, we report the
preparation of a flexible SiO2/SnO2 nanofibrous membrane (SiO2/SnO2 NFM) with
high surface area and hierarchical porous structure by selecting poly(vinyl
butyral) as pore-forming agent and embedding crystalline phase into amorphous
matrix without using surfactant as sacrificial template. Benefiting from the
uniform micropore size on the fibers and negatively charged properties, the
membranes exhibit a precise selectivity toward molecules based on electrostatic
interaction and size exclusion, which could separate organic molecule mixtures
with the same electrostatic charges and different molecular sizes with a high
efficiency of more than 97%. Furthermore, the highly tortuous open-porous
structures and high porosity give rise to a high permeate flux of 288 000 L m-2 h
1. In addition, the membrane also displays excellent stability and can be reused
for ten consecutive filtration-regeneration cycles. The integration of high
filtration efficiency, large permeate flux, good reutilization, and easy to
industrialization provides the SiO2/SnO2 NFM for potential applications in
practical molecular purification and separation science.
PMID- 28509530
TI - Role of Modulators in Controlling the Colloidal Stability and Polydispersity of
the UiO-66 Metal-Organic Framework.
AB - Nanoscale UiO-66 Zr6(OH)4O4(C8O4H4)6 has been synthesized with a series of
carboxylic acid modulators, R-COOH (where R = H, CH3, CF3, and CHCl2). The phase
purity and size of each MOF was confirmed by powder X-ray diffraction, BET
surface area analysis, and scanning transmission electron microscopy (STEM). Size
control of UiO-66 crystals from 20 nm to over 1 MUm was achieved, and confirmed
by STEM. The colloidal stability of each MOF was evaluated by dynamic light
scattering and was found to be highly dependent on the modulator conditions
utilized in the synthesis, with both lower pKa and higher acid concentration
resulting in more stable structures. Furthermore, STEM was carried out on both
colloidally stable samples and those that exhibited a large degree of
aggregation, which allowed for visualization of the different degrees of
dispersion of the samples. The use of modulators at higher concentrations and
with lower pKas leads to the formation of more defects, as a consequence of
terephthalic acid ligands being replaced by modulator molecules, thereby
enhancing the colloidal stability of the UiO-66 nanoparticles. These findings
could have a significant impact on nanoscale MOF material syntheses and
applications, especially in the areas of catalysis and drug delivery.
PMID- 28509532
TI - Nanodiamonds Mediate Oral Delivery of Proteins for Stem Cell Activation and
Intestinal Remodeling in Drosophila.
AB - Introduction of exogenous biomacromolecules into living systems is of great
interest in genome editing, cancer immunotherapy, and stem cell reprogramming.
Whereas current strategies generally depend on nucleic acids transfection, direct
delivery of functional proteins that provides enhanced specificity, increased
safety, and fast and temporal regulation is highly desirable. Nevertheless,
intracellular delivery of intact and bioactive proteins, especially in vivo,
remains poorly explored. In this study, we developed a nanodiamonds (NDs)-based
protein delivery system in cultured cells and in Drosophila that showed high
adsorption, high efficiency, and effective cytosolic release of fully functional
proteins. Through live-cell imaging, we observed a novel phenomenon wherein a
substantial amount of internalized NDs-protein complex rejected fusion with the
early endosome, thereby evading protein degradation in the lysosome. More
significantly, we demonstrated that dietary NDs-RNase induced apoptosis in
enterocytes, stimulating regenerative divisions in intestinal stem cells and
increasing the number of stem cells and precursor cells in Drosophila intestine.
As stem cells are poorly accessible by exogenous agents in vivo, NDs-mediated
oral delivery of proteins provides a new approach to modulate the stem cell
microenvironment for intestinal remodeling, which has important implications for
colorectal cancer therapy and regenerative medicine.
PMID- 28509533
TI - Low-Cost Label-Free Biosensing Bimetallic Cellulose Strip with SILAR-Synthesized
Silver Core-Gold Shell Nanoparticle Structures.
AB - We introduce a label-free biosensing cellulose strip sensor with surface-enhanced
Raman spectroscopy (SERS)-encoded bimetallic core@shell nanoparticles. Bimetallic
nanoparticles consisting of a synthesis of core Ag nanoparticles (AgNP) and a
synthesis of shell gold nanoparticles (AuNPs) were fabricated on a cellulose
substrate by two-stage successive ionic layer absorption and reaction (SILAR)
techniques. The bimetallic nanoparticle-enhanced localized surface plasmon
resonance (LSPR) effects were theoretically verified by computational
calculations with finite element models of optimized bimetallic nanoparticles
interacting with an incident laser source. Well-dispersed raspberry-like
bimetallic nanoparticles with highly polycrystalline structure were confirmed
through X-ray and electron analyses despite ionic reaction synthesis. The
stability against silver oxidation and high sensitivity with superior SERS
enhancement factor (EF) of the low-cost SERS-encoded cellulose strip, which
achieved 3.98 * 108 SERS-EF, 6.1%-RSD reproducibility, and <10%-degraded
sustainability, implicated the possibility of practical applications in high
analytical screening methods, such as single-molecule detection. The remarkable
sensitivity and selectivity of this bimetallic biosensing strip in determining
aquatic toxicities for prohibited drugs, such as aniline, sodium azide, and
malachite green, as well as monitoring the breast cancer progression for urine,
confirmed its potential as a low-cost label-free point-of-care test chip for the
early diagnosis of human diseases.
PMID- 28509534
TI - Analysis of Three Epoetin Alpha Products by LC and LC-MS Indicates Differences in
Glycosylation Critical Quality Attributes, Including Sialic Acid Content.
AB - Erythropoietin (EPO) is one of the main therapeutics used to treat anemic
patients, greatly improving their quality of life. In this study, biosimilars
Binocrit and a development product, called here CIGB-EPO, were compared to the
originator product, Eprex. All three are epoetin alpha products, reputed to have
similar glycosylation profiles. The quality, safety, and efficacy of this
biotherapeutic depend on the following glycosylation critical quality attributes
(GCQAs): sialylation, N-glycolyl-neuraminic acid (Neu5Gc) content, branching, N
acetyl-lactosamine (LacNAc) extensions, and O-acetylation pattern. Reverse-phase
ultra-high-pressure liquid chromatography (RP-UHPLC) analysis of acid-released,
1,2-diamino-4,5-methylenedioxybenzene (DMB) labeled sialic acid derivatives and
hydrophilic interaction liquid chromatography (HILIC) in combination with mass
spectrometry (HILIC-UHPLC-MS) of procainamide (PROC) labeled N-glycans were the
analytical tools used. An automated method for enzymatic release and PROC
labeling was applied for the first time to the erythropoiesis stimulating agent
(ESA) products, which facilitated novel, in-depth characterization, and allowed
identification of precise structural features including the location of O-acetyl
groups on sialic acid (SA) moieties. Samples were digested by a sialate-O
acetylesterase (NanS) to confirm the presence of O-acetyl groups. It was found
that Eprex contained the greatest relative abundance of O-acetylated derivatives,
Binocrit expressed the least Neu5Gc, and CIGB-EPO showed the greatest variety of
high-mannose-phosphate structures. The sialylation and LacNAc extension patterns
of the three ESAs were similar, with a maximum of four N-acetyl-neuraminic acid
(Neu5Ac) moieties detected per glycan. Such differences in SA derivatization,
particularly O-acetylation, could have consequences for the quality and safety of
a biotherapeutic, as well as its efficacy.
PMID- 28509535
TI - Molybdenum-Tungsten Mixed Oxide Deposited into Titanium Dioxide Nanotube Arrays
for Ultrahigh Rate Supercapacitors.
AB - A novel method involving the fabrication of Mo-W mixed oxide (MoxW1-xO3) is
proposed to modify the modest reaction kinetics and poor cycling stability of
MoO3 material. By a simple coelectrodeposition method, a series of MoxW1-xO3
oxides is deposited on a TiO2 nanotube array substrate. Because of the
differences between Mo6+ and W6+ in nature, there is significant distortion
existing in the mixed oxides, leading to their decreased crystallite size and
enlarged lattice space, which facilitates ion diffusion in the solid. As results,
the mixed oxides show much better balance between specific capacitance and
cycling stability than the bare MoO3 or WO3 sample, which suffers from either
poor cycling stability or low electrochemical activity. Impressively, the optimal
Mo-W mixed oxide exhibits a high specific capacitance of 517.4 F g-1 at 1 A g-1,
and, moreover, it retains 89.3% of the capacitance even at a high current density
of 10 A g-1, demonstrating ultrahigh rate capability. These findings reveal the
potential of the Mo-W mixed oxide for constructing advanced ultrahigh power
supercapacitors.
PMID- 28509536
TI - Long-Lived Polypyridyl Based Mononuclear Ruthenium Complexes: Synthesis,
Structure, and Azo Dye Decomposition.
AB - Two mononuclear ruthenium complexes [(bpy)2RuIIL1/L2](ClO4)2 ([1]2+/[2]2+) (bpy
2,2' bipyridine, L1 = 2,3-di(pyridin-2-yl)pyrazino[2,3-f][1,10]phenanthroline)
and L2 = 2,3-di(thiophen-2-yl)pyrazino[2,3-f][1,10]phenanthroline have been
synthesized. The complexes have been characterized using various analytical
techniques. The complex [1]2+ has further been characterized by its single
crystal X-ray structure suggesting ruthenium is coordinating through the N donors
of phenanthroline end. Theoretical investigation suggests that the HOMOs of both
complexes are composed of pyridine and pyrazine unit of ligands L1 and L2 whereas
the LUMOs are formed by the contribution of bipyridine units. The low energy
bands at ~480 nm of the complexes can be assigned as MLCT with partial
contribution from ligand transitions, whereas the rest are ligand centered. The
complexes have shown RuII/RuIII oxidation couples at E1/2 at 1.26 (70 mV) V and
1.28 (62 mV) V for [1]2+ and [2]2+ vs Ag/AgCl, respectively, suggesting no
significant role of distal thiophene or pyridine units of the ligands. The
complexes are emissive and display solvent dependent emission properties. Both
complexes have shown highest emission quantum yield and lifetime in DMSO (phi =
0.05 and tauavg = 460 ns and lambdamaxem at 620 nm for [1]2+; phi = 0.043 and
tauavg = 425 ns and lambdamaxem at 635 nm for [2]2+). Further, the long
luminescent lifetime of these complexes has been utilized to generate reactive
oxygen species for efficient azo dye decomposition.
PMID- 28509537
TI - [(18-C-6)K][(N=C)CuI-SiMe2Ph], a Potassium Silylcyanocuprate as a Catalyst Model
for Silylation Reactions with Silylboranes: Syntheses, Structures, and Catalytic
Properties.
AB - CuI-catalyzed silylation reactions involving silylboranes (in particular, pinB
SiMe2Ph (1)) as silyl sources have recently gained considerable attention. One of
the most efficient and versatile and yet simplest catalyst systems consists of
CuCN/NaOMe; however, nothing is known about the catalytically relevant species.
Using an NHC-based model catalyst, copper silyl complexes of the type [(NHC)Cu
SiMe2Ph] have been established to be crucial species in these catalytic
processes. The well-defined and spectroscopically and structurally characterized
complex [(18-C-6)K][NC-Cu-OtBu] (2), as a model for the catalytic system,
CuCN/NaOMe, shows comparable catalytic activity toward established, exemplary
substrates (aldehydes, imines, alpha,beta-unsaturated carbonyls) and in extension
allows the efficient silylation of ketones. In addition, a number of
peculiarities of the catalytic reaction are readily rationalized on the basis of
the mechanistic insight already established using [(NHC)Cu-SiMe2Ph] as a model
catalyst. Analogously to the NHC model system, the reaction of 2 with the
silylborane 1 furnishes the silylcyanocuprate [(18-C-6)K][NC-Cu-SiMe2Ph] (3) as a
potential crucial intermediate in these silylation reactions also suggesting
mechanistic similarities between (NHC)Cu- and CuCN/NaOMe-based catalyst systems.
Moreover, 3 and [(NHC)Cu-SiMe2Ph] complexes also share structurally distinctive
features. In the solid state 3 either exists as a linear, two-coordinated copper
complex or, depending on the conditions of crystallization, forms binuclear MU
silyl bridged dimers exhibiting very short Cu...Cu distances. Both structural
motifs are also known for [(NHC)Cu-SiR3] complexes. These findings give an
initial insight into the versatile structural chemistry of certain
silylcyanocuprates; in particular, the finding of dinuclear silylcuprates gives
rise to the question whether these dimeric species are of mechanistic relevance
for the catalytic processes. However, all peculiarities of the investigated
catalytic reaction can readily be rationalized on the basis of the mechanistic
details established using (NHC)Cu model complexes.
PMID- 28509538
TI - Bis(thiosemicarbazone) Complexes of Cobalt(III). Synthesis, Characterization, and
Anticancer Potential.
AB - Nine bis(thiosemicarbazone) (BTSC) cobalt(III) complexes of the general formula
[Co(BTSC)(L)2]NO3 were synthesized, where BTSC = diacetyl bis(thiosemicarbazone)
(ATS), pyruvaldehyde bis(thiosemicarbazone) (PTS), or glyoxal
bis(thiosemicarbazone) (GTS) and L = ammonia, imidazole (Im), or benzylamine
(BnA). These compounds were characterized by multinuclear NMR spectroscopy, mass
spectrometry, cyclic voltammetry, and X-ray crystallography. Their stability in
phosphate-buffered saline was investigated and found to be highly dependent on
the nature of the axial ligand, L. These studies revealed that complex stability
is primarily dictated by the axial ligand following the sequence NH3 > Im > BnA.
The cellular uptake and cytotoxicity in cancer cells were also determined. Both
the cellular uptake and cytotoxicity were significantly affected by the nature of
the equatorial BTSC. Complexes of ATS were taken up much more effectively than
those of PTS and GTS. The cytotoxicity of the complexes was correlated to that of
the free ligand. Cell uptake and cytotoxicity were also determined under hypoxic
conditions. Only minor differences in the hypoxia activity and uptake were
observed. Treatment of the cancer cells with the copper-depleting agent
tetrathiomolybdate decreased the cytotoxic potency of the complexes, indicating
that they may operate via a copper-dependent mechanism. These results provide a
structure-activity relationship for this class of compounds, which may be applied
for the rational design of new cobalt(III) anticancer agents.
PMID- 28509539
TI - Tunable Luminescent Lanthanide Supramolecular Assembly Based on Photoreaction of
Anthracene.
AB - Lanthanide luminescence materials generally show great superiority in light
emitting materials, gaining increasingly exploration in the design of advanced
functional materials. Herein, we prepared a supramolecular assembly via the
coordination of a host molecule (1) and dilanthanide metal. Compound 1 possesses
a 9,10-diphenylanthracene (ant) core with photosensitivity and terminal
terpyridine (tpy), containing two-arm dibenzo-24-crown-8. The assembly could
exhibit excellent lanthanide luminescence after undergoing a photoreaction from
anthracene unit in 1. Significantly, the luminescence of the assembly could be
reversibly switched on and off through a regulable photoreaction upon light
irradiation or heating. The multiple functional behavior combined with the ease
of assembly reveals that this photo/thermo-controlled lanthanide luminescence
supramolecular polymer design method offers a convenient pathway for future
engineering of multi-stimuli-responsive materials.
PMID- 28509540
TI - Characterization of the High-Spin Co(II) Intermediate Species of the O2-Evolving
Co4O4 Cubic Molecules.
AB - An artificial oxygen-evolving complex (OEC) contains a tetranuclear CoIII4O4
cubic cluster ligated with acetate and pyridine molecules, a light-activated
Ru(bpy)32+ moiety (bpy = 2,2'-bipyridine), and the sacrificial electron acceptor
S2O82- side. A recent EPR investigation of this system showed the formation of
the high-spin Co(II) ion under visible-illumination conditions. It has been
supported that this center originates from the cluster and is involved in the
oxygen-evolving process. The present report is focused on the further
characterization of the high-spin d7 configuration of the Co(II) species. The
measurement of the EPR spectrum at a wider magnetic field range in comparison to
that reported recently shows the presence of an additional signal that
contributes to the spectrum of the Co(II) center. The theoretical simulation of
this spectrum reveals that an isotropic g value and considerably small zero-field
splitting parameters describe the high-spin Co(II) ion in a unique way, which
supports a tetrahedral crystal field symmetry. On the basis of the spin
Hamiltonian parameters, the looping transitions that lead to the experimental EPR
signals are determined. Additionally, a possible role of the symmetry of the
Co(II) species and a proposed model that explains its formation during the O2
evolving process of the Co4O4 cubic molecules are discussed.
PMID- 28509541
TI - Synthesis, Characterization, and Variable-Temperature NMR Studies of Silver(I)
Complexes for Selective Nitrene Transfer.
AB - An array of silver complexes supported by nitrogen-donor ligands catalyze the
transformation of C?C and C-H bonds to valuable C-N bonds via nitrene transfer.
The ability to achieve high chemoselectivity and site selectivity in an amination
event requires an understanding of both the solid- and solution-state behavior of
these catalysts. X-ray structural characterizations were helpful in determining
ligand features that promote the formation of monomeric versus dimeric complexes.
Variable-temperature 1H and DOSY NMR experiments were especially useful for
understanding how the ligand identity influences the nuclearity, coordination
number, and fluxional behavior of silver(I) complexes in solution. These insights
are valuable for developing improved ligand designs.
PMID- 28509542
TI - Trimethylsulfonium Lead Triiodide: An Air-Stable Hybrid Halide Perovskite.
AB - We report on the synthesis, characterization, and optoelectronic properties of
the novel trimethylsulfonium lead triiodide perovskite, (CH3)3SPbI3. At room
temperature, the air-stable compound adopts a hexagonal crystal structure with a
1D network of face-sharing [PbI6] octahedra along the c axis. UV-vis reflectance
spectroscopy on a pressed pellet revealed a band gap of 3.1 eV, in agreement with
first-principles calculations, which show a small separation between direct and
indirect band gaps. Electrical resistivity measurements on single crystals
indicated that the compound behaves as a semiconductor. According to multi
temperature single-crystal X-ray diffraction, synchrotron powder X-ray
diffraction, Raman spectroscopy, and differential scanning calorimetry, two fully
reversible structural phase transitions occur at -5 and ca. -100 degrees C with
reduction of the unit cell symmetry to monoclinic as temperature decreases. The
role of the trimethylsulfonium cation regarding the chemical stability and
optoelectronic properties of the new compound is discussed in comparison with
APbI3 (A = Cs, methylammonium, and formamidinium cation), which are most commonly
used in perovskite solar cells.
PMID- 28509543
TI - Exploring the Gas-Phase Activation and Reactivity of a Ruthenium Transfer
Hydrogenation Catalyst by Experiment and Theory in Concert.
AB - This study elucidates structures, activation barriers, and the gas-phase
reactivity of cationic ruthenium transfer hydrogenation catalysts of the
structural type [(eta6-cym)RuX(pympyr)]+. In these complexes, the central
ruthenium(+II) ion is coordinated to an eta6-bound p-cymene (eta6-cym), a
bidentate 2-R-4-(2-pyridinyl)pyrimidine ligand (pympyr) with R = NH2 or N(CH3)2,
and an anion X = I-, Br-, Cl-, or CF3SO3-. We present infrared multiple-photon
dissociation (IR-MPD) spectra of precursors (before HCl loss) and of activated
complexes (after HCl loss), which elucidates C-H activation as the key step in
the activation mechanism. A resonant two-color IR-MPD scheme serves to record
several otherwise "dark" bands and enhances the validity of spectral assignments.
We show that collision-induced dissociation (CID)-derived activation energies of
the [(eta6-cym)RuX(pympyr)]+ (R = N(CH3)2) complexes depend crucially on the
anion X. The obtained activation energies for the HX loss correlate well with
quantum chemical activation barriers and are in line with the HSAB concept. We
further elucidate the reaction of the activated complexes with D2 under single
collision conditions. Quantum mechanical simulations substantiate that the
resulting species represent analogues for hydrido intermediates formed after
abstraction of H+ and H- from isopropanol, as postulated for the catalytic cycle
of transfer hydrogenation by us before.
PMID- 28509544
TI - Search for Electron Delocalization from [Fe(CN)6]3- to the Dication of Viologen
in (DNP)3[Fe(CN)6]2.10H2O.
AB - K3Fe(CN)6 reacts with the viologen 1,1'-bis(2,4-dinitrophenyl)-4,4'-bipyridinium
dication, (DNP)2+, to form a supramolecular complex, (DNP)3[Fe(CN)6]2.10H2O (1).
The crystal structure of 1 reveals that there are two [Fe(CN)6]3- anions within
an organic framework of three (DNP)2+ cations with the shortest Fe(III)...Fe(III)
distances of ca. 9.8 A, distances that minimize extensive long-range magnetic
exchange coupling interactions between the [Fe(CN)6]3- anions, and, thus, 1 is
paramagnetic above ca. 17 K and exhibits weak ferromagnetic coupling between 17
and 3 K and antiferromagnetic coupling between 3 and 1.8 K. The long
Fe(III)...Fe(III) distances permit slow spin-spin and slow spin-lattice
paramagnetic relaxation, relative to the iron-57 Larmor precession frequency, as
is evidenced by the Mossbauer spectra measured between 3 and 60 K; between 85 and
295 K, rapid paramagnetic relaxation is observed. Both the slow spin-spin and
slow spin-lattice relaxation are mediated by the organic, pi-conjugated viologen
cations. The Fe-C distances, the Mossbauer isomer shifts, the temperature
dependence of the magnetic susceptibility, and the 3 K magnetization results all
indicate the presence of low-spin Fe(III) ions in the [Fe(CN)6]3- anions in 1.
There is no unequivocal indication of the presence of any formal electron
delocalization or transfer from the [Fe(CN)6]3- anion to the (DNP)2+ cations in
the results obtained from X-ray crystallography, magnetic measurements, and
Mossbauer spectra. Because of enhancement of the spin-orbit coupling by the heavy
atom or -ion effect, the Fe(III) ions in the [Fe(CN)6]3- anions interact with the
(DNP)2+ cations, causing them to fluoresce with increasing intensity upon cooling
from 90 to 25 K when excited at 300 nm. The resulting luminescence of the
viologen (DNP)2+ cation induced by the [Fe(CN)6]3- anions indicates the presence
of significant mixing of the molecular orbitals derived from the [Fe(CN)6]3-
anions and the molecular orbitals associated with the (DNP)2+ cations to yield
bonding supramolecular orbitals in 1, a mixing that is also observed between 50
and 3 K in the temperature dependence of the isomer shift of 1.
PMID- 28509545
TI - Highly Coordinated Iron and Cobalt Nitrides Synthesized at High Pressures and
High Temperatures.
AB - Highly coordinated iron and cobalt nitrides were successfully synthesized via
direct chemical reaction between a transition metal and molecular nitrogen at
pressures above approximately 30 GPa using a laser-heated diamond anvil cell. The
synthesized novel transition metal nitrides were found to crystallize into the
NiAs-type or marcasite-type structure. NiAs-type FeN could be quenched at ambient
pressure, although it was gradually converted to the ZnS-type structure after the
pressure was released. On the other hand, CoN was recovered with ZnS-type
structure through a phase transition from NiAs-type structure at approximately a
few gigapascals during decompression. Marcasite-type CoN2 was also synthesized at
pressures above approximately 30 GPa. High-pressure in situ X-ray diffraction
measurement showed that the zero-pressure bulk modulus of marcasite-type CoN2 is
216(18) GPa, which is comparable to that of RhN2. This indicates that the
interatomic distance of the N-N dimer in marcasite-type CoN2 is short because of
weak orbital interaction between cobalt and nitrogen atoms, as in RhN2.
Surprisingly, a first-principles electronic band calculation suggests that the
NiAs-type FeN and CoN and marcasite-type CoN2 exhibit metallic characteristics
with magnetic moments of 3.4, 0.6, and 1.2 MUB, respectively. The ferromagnetic
NiAs-type structure originates from the anisotropic arrangement of transition
atoms stacked along the c axis.
PMID- 28509547
TI - Photoinduced Charge Shifts and Electron Transfer in Viologen-Tetraphenylborate
Complexes: Push-Pull Character of the Exciplex.
AB - Viologen-tetraarylborate ion-pair complexes were prepared and investigated by
steady-state and time-resolved spectroscopic techniques such as fluorescence and
femtosecond transient absorption. The results highlight a charge transfer
transition that leads to changes in the viologen structure in the excited singlet
state. Femtosecond transient absorption reveals the formation of excited-state
absorption and stimulated emission bands assigned to the planar (kobs < 1012 s-1)
and twisted (kobs ~ 1010 s-1) structures between two pyridinium groups in the
viologen ion. An efficient photoinduced electron transfer from the
tetraphenylborate anionic moiety to the viologen dication was observed less than
1 MUs after excitation. This is a consequence of the push-pull character of the
electron donor twisted viologen structure, which helps formation of the borate
triplet state. The borate triplet state is deactivated further via a second
electron transfer process, generating viologen cation radical (V*+).
PMID- 28509546
TI - Growth of Nitrosococcus-Related Ammonia Oxidizing Bacteria Coincides with
Extremely Low pH Values in Wastewater with High Ammonia Content.
AB - Ammonia oxidation decreases the pH in wastewaters where alkalinity is limited
relative to total ammonia. The activity of ammonia oxidizing bacteria (AOB),
however, typically decreases with pH and often ceases completely in slightly
acidic wastewaters. Nevertheless, nitrification at low pH has been reported in
reactors treating human urine, but it has been unclear which organisms are
involved. In this study, we followed the population dynamics of ammonia oxidizing
organisms and reactor performance in synthetic fully hydrolyzed urine as the pH
decreased over time in response to a decrease in the loading rate. Populations of
the beta-proteobacterial Nitrosomonas europaea lineage were abundant at the
initial pH close to 6, but the growth of a possibly novel Nitrosococcus-related
AOB genus decreased the pH to the new level of 2.2, challenging the perception
that nitrification is inhibited entirely at low pH values, or governed
exclusively by beta-proteobacterial AOB or archaea. With the pH shift, nitrite
oxidizing bacteria were not further detected, but nitrous acid (HNO2) was still
removed through chemical decomposition to nitric oxide (NO) and nitrate. The
growth of acid-tolerant gamma-proteobacterial AOB should be prevented, by keeping
the pH above 5.4, which is a typical pH limit for the N. europaea lineage.
Otherwise, the microbial community responsible for high-rate nitrification can be
lost, and strong emissions of hazardous volatile nitrogen compounds such as NO
are likely.
PMID- 28509548
TI - U(IV) Aqueous Speciation from the Monomer to UO2 Nanoparticles: Two Levels of
Control from Zwitterionic Glycine Ligands.
AB - The fate of U(IV)O2 in the environment in a colloidal form and its dissolution
and growth in controlled environments is influenced by organic ligation and redox
processes, where both affect solubility, speciation, and transport. Here we
investigate U(IV) aqueous speciation from pH 0 to 3 with the glycine (Gly)
ligand, the smallest amino acid. We document evolution of the monomeric to the
hexameric form from pH 0 to 3 via UV-vis spectroscopy and small-angle X-ray
scattering (SAXS). Crystals of the hexamer [U6O4(OH)4(H2O)6(HGly)12].12Cl
.12(H2O) (U6) were isolated at pH 2.15. The structure of U6 is a hexanuclear
oxo/hydroxo cluster U6O4(OH)4 decorated by 12 glycine ligands and 6 water
molecules. The effect of pH and temperature on U6 conversion to UO2
nanoparticles, or simply reversible aggregation, is detailed by transmission
electron microscopy imaging, in addition to SAXS and UV-spectroscopy. Because of
the zwitterion behavior of glycine, pH and temperature control over U(IV)
speciation is complex. Unexpectedly, stability of the polynuclear cluster
actually increases with increased pH. Speciation is sensitive to not only metal
oxo hydrolysis but also ligand lability and hydrophobic ligand-ligand
interactions.
PMID- 28509550
TI - Sugars Require Rigid Multivalent Displays for Activation of Mouse Sperm Acrosomal
Exocytosis.
AB - As a prerequisite to mammalian fertilization, the sperm acrosomal vesicle fuses
with the plasma membrane and the acrosome contents are exocytosed. Induction
occurs through engagement of the sperm receptors by multiple sugar residues.
Multivalent polymers displaying mannose, fucose, or GlcNAc are effective
synthetic inducers of mouse sperm acrosomal exocytosis (AE). Each carbohydrate is
proposed to have a distinct binding site on the sperm cell surface. To determine
the role of the scaffold structure in the efficiency of AE induction, different
polymer backbones were employed to display the different activating sugar
residues. These glycopolymers were prepared by ruthenium-catalyzed ring-opening
metathesis of 5-substituted norbornene or cyclooctene. The conformations of the
glycopolymers were characterized by small-angle X-ray scattering. Polynorbornene
displaying mannose, fucose, or GlcNAc forms flexible cylinders in aqueous
solution. However, polycyclooctenes displaying any of these same sugars are much
more flexible and form random coils. The flexible polycyclooctenes displaying
fucose or GlcNAc were less effective inducers of AE than their norbornene
counterparts. In contrast, polycyclooctene displaying mannose was the most
effective AE inducer and had a more collapsed spherelike structure. Our results
suggest that the AE efficacy of fucose, GlcNAc, and mannose polymers relies on a
relatively rigid polymer that can stabilize receptor signaling complexes.
PMID- 28509549
TI - Heterogeneous-Backbone Foldamer Mimics of Zinc Finger Tertiary Structure.
AB - A variety of oligomeric backbones with compositions deviating from
biomacromolecules can fold in defined ways. Termed "foldamers," these agents have
diverse potential applications. A number of protein-inspired secondary structures
(e.g., helices, sheets) have been produced from unnatural backbones, yet examples
of tertiary folds combining several secondary structural elements in a single
entity are rare. One promising strategy to address this challenge is the
systematic backbone alteration of natural protein sequences, through which a
subset of the native side chains is displayed on an unnatural building block to
generate a heterogeneous backbone. A drawback to this approach is that
substitution at more than one or two sites often comes at a significant energetic
cost to fold stability. Here we report heterogeneous-backbone foldamers that
mimic the zinc finger domain, a ubiquitous and biologically important metal
binding tertiary motif, and do so with a folded stability that is superior to the
natural protein on which their design is based. A combination of UV-vis
spectroscopy, isothermal titration calorimetry, and multidimensional NMR reveals
that suitably designed oligomers with >20% modified backbones can form native
like tertiary folds with metal-binding environments identical to the prototype
sequence (the third finger of specificity factor 1) and enhanced thermodynamic
stability. These results expand the scope of heterogeneous-backbone foldamer
design to a new tertiary structure class and show that judiciously applied
backbone modification can be accompanied by improvement to fold stability.
PMID- 28509551
TI - Significance of [2Fe-2S] Cluster N1a for Electron Transfer and Assembly of
Escherichia coli Respiratory Complex I.
AB - NADH:ubiquinone oxidoreductase, respiratory complex I, couples electron transfer
from NADH to ubiquinone with proton translocation across the membrane. NADH
reduces a noncovalently bound FMN, and the electrons are transported further to
the quinone reduction site by a 95 A long chain of seven iron-sulfur (Fe-S)
clusters. Binuclear Fe-S cluster N1a is not part of this long chain but is
located within electron transfer distance on the opposite site of FMN. The
relevance of N1a to the mechanism of complex I is not known. To elucidate its
role, we individually substituted the cysteine residues coordinating N1a of
Escherichia coli complex I by alanine and serine residues. The mutations led to a
significant loss of the NADH oxidase activity of the mutant membranes, while the
amount of the complex was only slightly diminished. N1a could not be detected by
electron paramagnetic resonance spectroscopy, and unexpectedly, the content of
binuclear cluster N1b located on a neighboring subunit was significantly
decreased. Because of the lack of N1a and the partial loss of N1b, the variants
did not survive detergent extraction from the mutant membranes. Only the C97AE
variant retained N1a and was purified by chromatographic steps. The preparation
showed a slightly diminished NADH/ferricyanide oxidoreductase activity, while the
NADH:decyl-ubiquinone oxidoreductase activity was not affected. N1a of this
preparation showed unusual spectroscopic properties indicating a different
ligation. We discuss whether N1a is involved in the physiological electron
transfer reaction.
PMID- 28509552
TI - Amino Acid Conjugated Anthraquinones from the Marine-Derived Fungus Penicillium
sp. SCSIO sof101.
AB - Emodacidamides A-H (1-8), natural products featuring anthraquinone-amino acid
conjugates, have been isolated from a marine-derived fungus, Penicillium sp.
SCSIO sof101, together with known anthraquinones 9 and 10. The planar structures
of 1-8 were elucidated using a combination of NMR spectroscopy and mass
spectrometry. The absolute configurations of the amino acid residues were
confirmed using Marfey's method and chiral-phase HPLC analyses. Additionally,
isolates were evaluated for possible immunomodulatory and cytotoxic activities.
Emodacidamides A (1), C (3), D (4), and E (5) inhibited interleukin-2 secretion
from Jurkat cells with IC50 values of 4.1, 5.1, 12, and 5.4 MUM, respectively.
PMID- 28509553
TI - Uncovering the Thermo-Kinetic Origins of Phase Ordering in Mixed-Valence Antimony
Tetroxide by First-Principles Modeling.
AB - Phase ordering in the mixed-valence oxide Sb2O4 has been examined by density
functional theory (DFT) calculations. We find that the ground-state total
energies of the two phases (alpha and beta) are almost degenerate and are highly
sensitive to the choice of the approximation to the exchange correlation (xc)
functional used in our calculations. Interestingly, with the inclusion of the
zero-point energy corrections, the alpha phase is predicted to be the ground
state polymorph for most xc functionals used. We also illustrate the pronounced
stereochemical activity of Sb in these polymorphs of Sb2O4, setting an exception
to the Keve and Skapski rule. Here, we find that the actual bonding in the alpha
phase is more asymmetric, while the anomalous stability of the beta phase could
be rationalized from kinetic considerations. We find a non-negligible activation
barrier for this alpha-beta phase transition, and the presence of a saddle point
(beta phase) supports the separation of Sb(III) over a continuous phase
transition, as observed in experiments.
PMID- 28509554
TI - "Self-Shaping" of Multicomponent Drops.
AB - In our recent study we showed that single-component emulsion drops, stabilized by
proper surfactants, can spontaneously break symmetry and transform into various
polygonal shapes during cooling [ Denkov Nature 2015 , 528 , 392 - 395 ]. This
process involves the formation of a plastic rotator phase of self-assembled oil
molecules beneath the drop surface. The plastic phase spontaneously forms a frame
of plastic rods at the oil drop perimeter which supports the polygonal shapes.
However, most of the common substances used in industry appear as mixtures of
molecules rather than pure substances. Here we present a systematic study of the
ability of multicomponent emulsion drops to deform upon cooling. The observed
trends can be summarized as follows: (1) The general drop-shape evolution for
multicomponent drops during cooling is the same as with single-component drops;
however, some additional shapes are observed. (2) Preservation of the particle
shape upon freezing is possible for alkane mixtures with chain length difference
Deltan <= 4; for greater Deltan, phase separation within the droplet is observed.
(3) Multicomponent particles prepared from alkanes with Deltan <= 4 plastify upon
cooling due to the formation of a bulk rotator phase within the particles. (4) If
a compound, which cannot induce self-shaping when pure, is mixed with a certain
amount of a compound which induces self-shaping, then drops prepared from this
mixture can also self-shape upon cooling. (5) Self-emulsification phenomena are
also observed for multicomponent drops. In addition to the three recently
reported mechanisms of self-emulsification [ Tcholakova Nat. Commun. 2017 , ( 8
), 15012 ], a new (fourth) mechanism is observed upon freezing for alkane
mixtures with Deltan > 4. It involves disintegration of the particles due to a
phase separation of alkanes upon freezing.
PMID- 28509556
TI - Structure-Based Selective Adsorption of Graphene on a Gel Surface: Toward
Improving the Quality of Graphene Nanosheets.
AB - Top-down graphene production via exfoliation from graphite produces a mass of
graphene with structural variation in terms of the number of layers, sheet size,
edge type, and defect density. All of these characteristics affect its electronic
structure. To develop useful applications of graphene, structural separation of
graphene is necessary. In this study, we investigate the adsorption behavior of
different types of graphene fragments using a multicolumn gel chromatography
system with a view to developing an efficient method for separating high-quality
graphene. The graphene was dispersed in an aqueous sodium dodecyl sulfate (SDS)
surfactant solution and flown through allyl-dextran-based gel columns connected
in series. In the chromatographic operation, we observed that the small-sized or
oxidized graphene fragments tended to bind to the gel and the relatively large
sized graphene with a low oxygen content eluted from the gel column. In this
system, the adsorbed SDS molecules on the graphitic surface prevented graphitic
materials from binding to the gel and the oxygen functional groups on the
graphene oxide or at the abundant edge of small-sized graphene hindered SDS
adsorption. We hypothesize that the reduced SDS adsorption density results in the
preferential adsorption of small-sized or oxidized graphene fragments on the gel.
This type of chromatographic separation is a cost-effective and scalable method
for sorting nanomaterials. The structural separation of graphene based on the
adsorption priority found in this study will improve the quality of graphene
nanosheets on an industrial scale.
PMID- 28509555
TI - Differential Phosphoproteomic Analysis of Recombinant Chinese Hamster Ovary Cells
Following Temperature Shift.
AB - Phosphorylation is one of the most important post-translational modifications,
playing a crucial role in regulating many cellular processes, including
transcription, cytoskeletal rearrangement, cell proliferation, differentiation,
apoptosis, and signal transduction. However, to date, little work has been
carried out on the phosphoproteome in CHO cells. In this study we have carried
out a large scale differential phosphoproteomic analysis of recombinant CHO cells
following a reduction of culture temperature (temperature shift). The reduction
of culture temperature during the exponential phase of growth is commonly
employed by the biopharmaceutical industry to increase product yield; however,
the molecular mechanisms of temperature shift in CHO cells remain poorly
understood. We have identified 700 differentially expressed phosphopeptides using
quantitative label-free LC-MS/MS phosphoproteomic analysis in conjunction with
IMAC and TiO2 phosphopeptide enrichment strategies, following a reduction in
temperature from 37 to 31 degrees C. Functional assessment of the
phosphoproteomic data using gene ontology analysis showed a significant
enrichment of biological processes related to growth (e.g., cell cycle, cell
division), ribosomal biogenesis, and cytoskeleton organization, and molecular
functions related to RNA binding, transcription factor activity, and protein
serine/threonine kinase activity. Differential phosphorylation of two proteins,
ATF2 and NDRG1, was confirmed by Western blotting. This data suggests the
importance of including the post-translational layer of regulation, such as
phosphorylation, in CHO "omics" studies. This study also has the potential to
identify phosphoprotein targets that could be modified using cell line
engineering approaches to improve the efficiency of recombinant protein
production.
PMID- 28509557
TI - Determination of Permeability Coefficients of Polymersomal Membranes for
Hydrophilic Molecules.
AB - Polymer vesicles, so-called polymersomes, can be applied as carrier-systems and
universal reaction compartments, due to the possibility to encapsulate guest
molecules. Compared to common lipid vesicles, polymersomes show an increased
stability and decreased membrane permeability. Control of the mass transport
across the membrane is necessary for any application, requiring the precise
knowledge of the permeability. So far, data on permeability coefficients of
polymersomal membranes are scarce because commonly applied release assays are
confronted with the challenge of high detection limits and alternative methods
developed so far are either restricted to the use of a certain permeating
molecule or rely on the use of nuclear magnetic resonance measurements. In
contrast, an influx assay that is broadly applicable to hydrophilic molecules and
does not involve specialized equipment was developed in this work, which is based
on the passive diffusion of compounds into initially empty vesicles. The method
is valid for hydrophilic molecules that show no membrane retention and, thus, do
not accumulate within the membrane. Using this method, the permeability of
polymersomes made of poly(2-methyloxazoline)15-poly(dimethylsiloxane)68-poly(2
methyloxazoline)15 for seven model compounds was investigated under varying
conditions. Permeability coefficients as low as 1.9 * 10-14 cm s-1 could be
measured.
PMID- 28509559
TI - Evaporation-Driven Deposition of ITO Thin Films from Aqueous Solutions with Low
Speed Dip-Coating Technique.
AB - We suggest a novel wet coating process for preparing indium tin oxide (ITO) films
from simple solutions containing only metal salts and water via evaporation
driven film deposition during low-speed dip coating. Homogeneous ITO precursor
films were deposited on silica glass substrates from the aqueous solutions
containing In(NO3)3.3H2O and SnCl4.5H2O by dip coating at substrate withdrawal
speeds of 0.20-0.50 cm min-1 and then crystallized by the heat treatment at 500
800 degrees C for 10-60 min under N2 gas flow of 0.5 L min-1. The ITO films
heated at 600 degrees C for 30 min had a high optical transparency in the
visible range and a good electrical conductivity. Multiple-coating ITO films
obtained with five-times dip coating exhibited the lowest sheet (rhoS) and volume
(rhoV) resistivities of 188 Omega sq-1 and 4.23 * 10-3 Omega cm, respectively.
PMID- 28509558
TI - Chiral Structures from Achiral Micellar Lyotropic Liquid Crystals under Capillary
Confinement.
AB - Recently, the emergence of spontaneous reflection-symmetry-broken configurations
in achiral chromonic liquid crystals confined in cylindrical capillaries with
homeotropic anchoring at the cylinder walls was reported, namely, the so-called
twisted-escaped radial (TER) and twisted planar polar (TPP) configurations. This
new example of spontaneous reflection symmetry breaking in liquid crystals was
attributed to the twist elastic modulus, which is known to be unusually small in
comparison to the splay and bend moduli in the case of chromonic liquid crystals.
We now report the experimental observation of reflection symmetry breaking in
cylindrical capillaries in the case of a classical, achiral, and nonchromonic
lyotropic liquid crystal forming a nematic phase of disklike micelles orienting
homeotropically at the capillary walls. We observed the same chiral TER
configuration, as well as a nonplanar twisted polar (TP) configuration. The TP
configuration is characterized by two half-unit so-called twist disclinations,
where the director twist around the line defects drives the formation of a double
helix of the disclinations along the axis of the capillary. Additionally, there
is a transverse twist between the two disclination lines with the same handedness
as the axial twist. Similarities with and differences from the case of chromonic
liquid crystals are discussed; in particular, we examine the conditions under
which spontaneous reflection symmetry breaking occurs in the nonchromonic system.
It seems that the chiral TER configuration can be stabilized by the presence of
point defects.
PMID- 28509560
TI - Multiscale Model for Electrokinetic Transport in Networks of Pores, Part II:
Computational Algorithms and Applications.
AB - The first part of this two-article series presented a robust mathematical model
for the fast and accurate prediction of electrokinetic phenomena in porous
networks with complex topologies. In the second part of this series, we first
present a numerical algorithm that can efficiently solve the model equations. We
then demonstrate that the resulting framework is capable of capturing a wide
range of transport phenomena in microstructures by considering a hierarchy of
canonical problems with increasing complexity. The developed framework is
validated against direct numerical simulations of deionization shocks in
micropore-membrane junctions and concentration polarization in micro- and
nanochannel systems. We demonstrate that for thin pores subject to concentration
gradients our model consistently captures correct induced osmotic pressure, which
is a macroscopic phenomena originally derived from thermodynamic principles but
here is naturally predicted through microscopic electrostatic interactions.
Moreover, we show that the developed model captures current rectification
phenomena in a conical nanopore subject to an axial external electric field.
Finally, we provide discussions on examples involving stationary and moving
deionization shocks in micropore nanopore T-junctions as well as induced-flow
loops when pores of varying sizes are connected in parallel.
PMID- 28509561
TI - Lattice and Valence Electronic Structures of Crystalline Octahedral Molybdenum
Halide Clusters-Based Compounds, Cs2[Mo6X14] (X = Cl, Br, I), Studied by Density
Functional Theory Calculations.
AB - The electronic and crystal structures of Cs2[Mo6X14] (X = Cl, Br, I) cluster
based compounds were investigated by density functional theory (DFT) simulations
and experimental methods such as powder X-ray diffraction, ultraviolet-visible
spectroscopy, and X-ray photoemission spectroscopy (XPS). The experimentally
determined lattice parameters were in good agreement with theoretically optimized
ones, indicating the usefulness of DFT calculations for the structural
investigation of these clusters. The calculated band gaps of these compounds
reproduced those experimentally determined by UV-vis reflectance within an error
of a few tenths of an eV. Core-level XPS and effective charge analyses indicated
bonding states of the halogens changed according to their sites. The XPS valence
spectra were fairly well reproduced by simulations based on the projected
electron density of states weighted with cross sections of Al Kalpha, suggesting
that DFT calculations can predict the electronic properties of metal-cluster
based crystals with good accuracy.
PMID- 28509562
TI - Thiolate Spin Population of Type I Copper in Azurin Derived from 33S Hyperfine
Coupling.
AB - The electron transfer mediating properties of type I copper proteins stem from
the intricate ligand coordination sphere of the Cu ion in their active site.
These redox properties are in part due to unusual cysteine thiol coordination,
which forms a highly covalent copper-sulfur (Cu-S) bond. The structure and
electronic properties of type I copper have been the subject of many experimental
and theoretical studies. The measurement of spin delocalization of the Cu(II)
unpaired electron to neighboring ligands provides an elegant experimental way to
probe the fine details of the electronic structure of type I copper. To date, the
crucial parameter of electron delocalization to the sulfur atom of the cysteine
ligand has not been directly determined experimentally. We have prepared 33S
enriched azurin and carried out W-band (95 GHz) electron paramagnetic resonance
(EPR) and electron-electron double resonance detected NMR (EDNMR) measurements
and, for the first time, recorded the 33S nuclear frequencies, from which the
hyperfine coupling and the spin population on the sulfur of the thiolate ligand
were derived. The overlapping 33S and 14N EDNMR signals were resolved using a
recently introduced two-dimensional correlation technique, 2D-EDNMR. The 33S
hyperfine tensor was determined by simulations of the EDNMR spectra using 33S
hyperfine and quadrupolar tensors predicted by QM/MM DFT calculations as starting
points for a manual spectral fit procedure. To reach a reasonable agreement with
the experimental spectra, the 33S hyperfine principal value, Az, and one of the
corresponding Euler angles had to be modified. The final values obtained gave an
experimentally determined sulfur spin population of 29.8 +/- 0.7%, significantly
improving the wide range of 29-62% reported in the literature. Our direct,
experimentally derived value now provides an important constraint for further
theoretical work aimed at unravelling the unique electronic properties of this
site.
PMID- 28509563
TI - The Adjunctive Soft-Tissue Diode Laser in Orthodontics.
AB - Lasers are a relatively new addition to the orthodontist's armamentarium. This
article reviews the fundamental basic science of available soft-tissue lasers,
with an emphasis on diode lasers, and discusses various adjunct applications of
the diode laser for soft-tissue orthodontic procedures. Diode lasers function by
cutting with an initiated hot tip and produce minimal to no interaction with
healthy dental hard tissue, making them suitable for soft-tissue procedures. The
contact cutting mode provides enhanced bloodless site visibility and facility to
perform delicate soft tissue procedures, which is important in areas with
difficult access. Such adjunctive uses include laser gingivectomy to improve oral
hygiene or bracket positioning, esthetic laser gingival recontouring, and laser
exposure of superficially impacted teeth. Selected cases treated with a 940-nm
indium-gallium-arsenide-phosphide (InGaAsP) diode laser will be presented.
PMID- 28509565
TI - A qualitative meta-summary using Sandelowski and Barroso's method for integrating
qualitative research to explore barriers and facilitators to self-care in heart
failure patients.
AB - BACKGROUND: Individual qualitative studies provide varied reasons for why heart
failure patients do not engage in self-care, yet articles that aggregated primary
studies on the subject have methodological weaknesses that justified the
execution of a qualitative meta-summary. AIM: The aim of this study is to
integrate the findings of qualitative studies pertaining to barriers and
facilitators to self-care using meta-summary techniques. METHODS: Qualitative
meta-summary techniques by Sandelowski and Barroso were used to combine the
findings of qualitative studies. Meta-summary techniques include: (1) extraction
of relevant statements of findings from each report; (2) reduction of these
statements into abstracted findings and (3) calculation of effect sizes.
Databases were searched systematically for qualitative studies published between
January 2010 and July 2015. Out of 2264 papers identified, 31 reports based on
the accounts of 814 patients were included in the meta-summary. RESULTS: A total
of 37 statements of findings provided a comprehensive inventory of findings
across all reports. Out of these statements of findings, 21 were classified as
barriers, 13 as facilitators and three were classed as both barriers and
facilitators. The main themes relating to barriers and facilitators to self-care
were: beliefs, benefits of self-care, comorbidities, financial constraints,
symptom recognition, ethnic background, inconsistent self-care, insufficient
information, positive and negative emotions, organizational context, past
experiences, physical environment, self-initiative, self-care adverse effects,
social context and personal preferences. CONCLUSION: Based on the meta-findings
identified in this study, future intervention development could address these
barriers and facilitators in order to further enhance self-care abilities in
heart failure patients.
PMID- 28509564
TI - Maternal Time Use and Nurturing: Analysis of the Association Between
Breastfeeding Practice and Time Spent Interacting with Baby.
AB - BACKGROUND: Breastfeeding supports child development through complex mechanisms
that are not well understood. Numerous studies have compared how well
breastfeeding and nonbreastfeeding mothers interact with their child, but few
examine how much interaction occurs. SUBJECTS AND METHODS: Our study of weekly
time use among 156 mothers of infants aged 3-9 months investigated whether
lactating mothers spend more time providing emotional support or cognitive
stimulation of their infants than nonbreastfeeding mothers, and whether the
amount of such interactive time is associated with breastfeeding intensity.
Mothers were recruited via mother's and baby groups, infant health clinics, and
childcare services, and used an electronic device to record their 24-hour time
use for 7 days. Sociodemographic and feeding status data were collected by
questionnaire. Statistical analysis using linear mixed modeling and residual
maximum likelihood analysis compared maternal time use for those giving "some
breastfeeding" and those "not breastfeeding." Analysis was also conducted for
more detailed feeding subgroups. RESULTS: Breastfeeding and nonbreastfeeding
mothers had broadly similar socioeconomic and demographic characteristics.
Breastfeeding was found to be associated with more mother-child interaction time,
a difference only partially explained by weekly maternal employment hours or
other interactive care activities such as play or reading. CONCLUSION: This study
presents data suggesting that lactating mothers spent significantly more hours
weekly on milk feeding and on carrying, holding, or soothing their infant than
nonlactating mothers; and on providing childcare. Understanding the mechanisms by
which child mental health and development benefits from breastfeeding may have
important implications for policies and intervention strategies, and could be
usefully informed by suitably designed time use studies.
PMID- 28509566
TI - Respiratory motion during 90Yttrium PET contributes to underestimation of tumor
dose and overestimation of normal liver tissue dose.
AB - Background Yttrium-90 dosimetry after radioembolization is reliant on accurate
quantitative imaging of the microsphere deposition. Previous studies have focused
on the correction of geometrical resolution effects. Purpose To uncover
additional effects of respiratory motion. Material and Methods Mathematical
models describing spherical tumors were formed and two blurring effects, limited
geometrical resolution and respiratory motion, were simulated. The virtual images
were used as basis for dose volume histogram estimations by convolving the
radioactivity representations with a dose point kernel. Results For respiratory
motion only, the largest errors were found for the smallest tumors and/or tumors
with heterogeneous distribution of yttrium-90 microspheres. The deviations in max
dose and dose to 25% and 50% of the tumor volume were estimated at 20-40%, 10
30%, and 0-30%, respectively. Additional blurring from geometrical resolution
increased the errors to 55-75%, 50-60%, and 25-60%, respectively. Conclusion
Respiratory motion contributes to underestimation of tumor dose and
overestimation of normal tissue dose.
PMID- 28509567
TI - Early evaluation of radiation-induced parotid damage with diffusion kurtosis
imaging: a preliminary study.
AB - Background Radiation-induced parotid gland damage is a common complication of
radiotherapy (RT) in patients with nasopharyngeal carcinoma (NPC), which always
causes xerostomia, dysphagia, dental caries, and even sleep disorders. Early
evaluation of radiation-induced parotid damage is required to facilitate early
interventions. Purpose To early-evaluate radiation-induced parotid damage using
diffusion kurtosis imaging (DKI) in patients with NPC undergoing RT. Material and
Methods Thirty-two patients with NPC underwent DKI for parotid glands pre-RT (two
weeks before RT), mid-RT (five weeks after RT began), and post-RT (four weeks
after RT). Parotid volume, apparent diffusion coefficient (ADC), corrected
diffusion coefficient (D), excess diffusion kurtosis coefficient (K) values, mean
radiation dose, and xerostomia degrees were recorded and analyzed. Results During
RT, parotid ADC (change rates = 41.3 +/- 25.2% at mid-RT, 70.8 +/- 34.3% at post
RT) and D (change rates = 41.9 +/- 25.2% at mid-RT, 63.2 +/- 30.2% at post-RT)
increased, while parotid volume (atrophy rates = 31.5 +/- 7.9% at mid-RT, 30.6 +/
10.3% at post-RT) and K (change rates = -17.8 +/- 11.0% at mid-RT, -29.8 +/-
9.0% at post-RT) decreased significantly (all P < 0.001). At post-RT, the change
rate of parotid D values was significantly positively correlated with the mean
radiation dose ( r = 0.455, P < 0.001). Parotid ADC, D, and K values showed
excellent intra- and inter-observer agreement (intraclass correlation coefficient
= 0.946-0.985). Conclusion Radiation-induced parotid damage in patients with NPC
undergoing RT could be effectively evaluated by DKI in the early stage.
PMID- 28509568
TI - Low body weight and clinical outcomes in acute coronary syndrome patients:
results of the ACHILLES Registry.
AB - BACKGROUND: Being overweight increases the risk of cardiovascular diseases and
mortality. However, among high-body-weight patients with established acute
coronary syndrome (ACS) this evidence is not clear. In this scenario, a low body
weight (LBW) has been proposed to confer higher prognostic risk and higher
bleeding risk with new P2Y12 inhibitors. AIMS: We aimed to examine differences in
mortality, catheterizations/revascularizations, antiplatelet therapy and
ischemic/bleeding adverse events between ACS patients with LBW. METHODS: This is
a multicenter registry involving 1576 consecutive ACS patients (ST-elevation
myocardial infarction (STEMI), non-STEMI, or unstable angina) from three tertiary
institutions. Patients were divided into two groups: LBW (weight < 60 kg, n =
176) and non-LBW (weight ? 60 kg, n = 1400). During 12 months follow-up, we
recorded management (catheterizations/revascularizations), antiplatelet therapy,
major adverse cardiovascular events (MACEs), bleeding events (BARC
classification), and mortality. RESULTS: Catheterizations (86.4% vs. 93.4%; p =
0.001) and revascularizations (64.8% vs. 76.1%; p = 0.001) were significantly
lower in the LBW group. At discharge, prescription of new P2Y12 inhibitors was
also lower in LBW patients (24.4% vs. 37.8%; p = 0.001). After 12-month follow
up, the incidence of MACE (HR 1.61 (95% CI 1.03-2.50]; p = 0.038) and mortality
(HR 2.18 (95% CI 1.33-3.58); p = 0.002) was higher in LBW patients compared with
non-LBW. In contrast, there were no significant differences for bleeding events.
CONCLUSIONS: LBW in ACS patients was associated with higher incidence of MACE and
mortality. In this group of patients less catheterizations and coronary
revascularizations were performed. Despite there being no differences in bleeding
rates, new P2Y12 inhibitors were less prescribed in LBW patients.
PMID- 28509569
TI - HIV-1 CRF07_BC with a Seven Amino Acid Deletion in the gag p6 Region Dominates in
HIV-1-Infected Men Who Have Sex with Men in China.
AB - We examined sequence variation in the HIV-1 gag p6 region from 27 individuals
infected with HIV-1 CRF07_BC. An additional 269 gag p6 sequences of CRF07_BC from
the Los Alamos National Laboratory database were also analyzed. A unique deletion
of seven amino acid (aa) (p6Delta7) (aa 30-36, PIDKELY, in the HXB2 genome) was
observed to exist exclusively in CRF07_BC. Indeed, 54.1% (160/296) of the
CRF07_BC sequences contained the p6Delta7 mutation. The prevalence of the
p6Delta7 mutation was 37.2% (29/78) and 92.3% (48/52) in CRF07_BC-infected
intravenous drug users and men who have sex with men (MSM), respectively. Our
results demonstrate that the p6Delta7 mutation dominates in MSM infected by HIV-1
CRF07_BC in China and suggests that this deletion could serve as a useful marker
for monitoring HIV-1 evolution and epidemic. In future studies, it will be of
interest to determine whether such genotypic variation influences viral
replication capacity and disease progression.
PMID- 28509570
TI - Learners' perspectives on the provision of condoms in South African public
schools.
AB - A stubborn health challenge for learners in South African public schools concerns
sexual and reproductive health and rights (SRHR). In 2015, the Department of
Basic Education (DBE) proposed the provision of condoms and SRHR-services to
learners in schools. This study aimed to contribute to the finalisation and
implementation of DBE's policy by exploring learners' perspectives on the
provision of condoms and SRHR-services in schools. Sixteen focus group
discussions were conducted with learners (n = 116) from 33 public schools, to
assess their attitudes, social influences, and needs and desires regarding condom
provision and SRHR-services in schools. The majority of learners did not support
condom provision in schools as they feared that it may increase sexual activity.
Contrarily, they supported the provision of other SRHR-services as clinics fail
to offer youth-friendly services. Learners' sexual behaviour and access to SRHR
services are strongly determined by their social environment, including
traditional norms and values, and social-pressure from peers and adults.
Learners' most pressing needs and desires to access condoms and SRHR-services in
school concerned respect, privacy and confidentiality of such service provision.
Implementation of DBE's policy must be preceded by an evidence-informed advocacy
campaign to debunk myths about the risk of increased sexual activity, to advocate
for why such services are needed, to shift societal norms towards open discussion
of adolescent SRHR and to grapple with the juxtaposition of being legally
empowered but socially inhibited to protect oneself from HIV, STIs and early
pregnancy. Provision of condoms and other SRHR-services in schools must be
sensitive to learners' privacy and confidentiality to minimise stigma and
discrimination.
PMID- 28509571
TI - Numerical Study of Novel Ratiometric Sensors Based on Plasmon-Exciton Coupling.
AB - We numerically studied the optical properties of spherical nanostructures made of
an emitter core coated by a silver shell through the generalized Mie theory. When
there is a strong coupling between the localized surface plasmon in the metallic
shell and the emitter exciton in the core, the extinction spectra exhibit two
peaks. Upon adsorption of analytes on these core-shell nanostructures, the
intensities of the two peaks change with opposite trends. This property makes
them potential sensitive ratiometric sensors. Molecule adsorption on these
nanostructures can be quantified through a very simple optical configuration
likely resulting in a much faster acquisition time compared with systems based on
the traditional metal nanoparticle surface plasmon resonance (SPR) biosensors.
PMID- 28509572
TI - Effect of silibinin-loaded nano-niosomal coated with trimethyl chitosan on miRNAs
expression in 2D and 3D models of T47D breast cancer cell line.
AB - Silibinin is a natural flavonoid with a strong antioxidant property and weak
cytotoxic activity. It has demonstrated anti-tumoural activity against many types
of malignancies; however, due to its hydrophobic structure, it has poor water
solubility, bioavailability and permeability across intestinal epithelial cells.
To improve the effect of silibinin, we have vehiculated silibinin by a highly
stable niosomal nanostructure based on a Span 60/cholesterol (CH)/N-trimethyl
chitosan (TMC) system in order to study its potential application for the
delivery of silibinin in T47D cultured under three-dimensional (3D) and two
dimensional (2D) conditions. To study the effect of nanodrug on miRNAs
expression, we evaluated quantitative expression of miRNA-21 and miRNA-15a as
well as miR-141 and miR-200c which act as oncogene and tumour suppressors by real
time PCR. Results demonstrated that the mechanism of nanodrug action as well as
the response of tumour cells differed in 3D culture as compared to 2D. Delivery
of silibinin-loaded niosomes coated with TMC was found to be more effective in
inhibiting the growth of tumour cells and inducing apoptosis than free silibinin
administration. In silibinin-treated cells, death occurred in a dose- and time-
dependent manner by induction of apoptosis and alteration of the cell cycle. Real
time PCR analysis revealed a decrease in miR-21, miR-15a and miR-141while
increase in miR-200c expression levels was observed in silibinin-treated cells
relative to the levels in the untreated cells. The results show that nanodrug
delivery was more effective than free silibinin administration in changing the
level of miRNAs expression in cancer cells. Therefore, niosomal nanostructure
with TMC could be a suitable vehicle for hydrophobic compounds, such as
silibinin, by improving their action in cancer therapy.
PMID- 28509574
TI - Improving the Early Initiation of Breastfeeding: The WHO-UNICEF Breastfeeding
Advocacy Initiative.
PMID- 28509573
TI - Adverse Events of Atomoxetine in a Double-Blind Placebo-Controlled Study in
Children with Autism.
AB - OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) symptoms, including
inattention and over activity, occur in approximately one-third of children with
autism spectrum disorder (ASD). We describe the rate and duration of adverse
events in a randomized controlled trial of atomoxetine (ATX) and parent training
(PT) for ADHD symptoms and noncompliance in children with ASD. METHODS: We
conducted a 10-week, double-blind, 2 * 2 trial of ATX and PT with 128 children
(ages 5-14) randomized to ATX alone, ATX+PT, placebo+PT, or placebo alone. For 6
weeks, ATX (or placebo) doses were clinically adjusted to a maximum of 1.8
mg/(kg.day) and maintained for an additional 4 weeks. An average of seven PT
sessions were conducted in the two PT arms. Adverse events (AEs) were assessed
through parent ratings of common symptoms on a seven-point Likert severity scale
and through direct interviews with study medical staff. RESULTS: ATX was
associated with decreased appetite and fatigue, but was otherwise well tolerated.
Most reported AEs lasted 4 weeks or less. Unlike reports with typically
developing (TD) children, there were no concerns with QTc changes or suicidal
ideation. CONCLUSIONS: This study extends the findings of previous studies of ATX
in ASD by documenting that the type of AEs was similar to that of TD children,
with no significant safety concerns.
PMID- 28509575
TI - Haploidentical hematopoietic stem cell transplantation with myeloablative
conditioning regimen could serve as an optional salvage therapy for younger
patients with refractory or relapsed aggressive non-Hodgkin lymphoma.
PMID- 28509576
TI - HER2 positivity may confer resistance to therapy with paclitaxel in breast cancer
cell lines.
AB - INTRODUCTION: MicroRNAs (miRNAs) are short non-coding single-stranded RNAs.
Involving in post-transcriptional gene silencing, miRNAs are thought to play
important roles in many cancers such as breast cancer. Paclitaxel is used widely
in the treatment of breast cancer. In this study, we investigated the effect of
paclitaxel treatment on the expression levels of two oncomirs (oncomiRs), miR-21
and miR-203, in breast cancer cell lines. MATERIALS AND METHODS: MTT assay was
performed to determine IC50 of paclitaxel for human breast cancer cell lines
including MCF-7, MDA-MB-231, SKBR3 and BT-474. After RNA extraction and cDNA
synthesis, the expression levels of miRNAs were then quantitatively evaluated
using real-time PCR. RESULTS: Our results showed that after treatment, the
expression levels of both miR-21 and miR-203 were significantly increased in HER2
positive cell lines, BT-474 and SKBR3. HER2-negative cell lines, MCF-7 and MDA-MB
231, in contrast had significantly decreased expression of both assessed
oncomiRs. CONCLUSION: Our results showed that the expression levels of oncomiRs
were increased in HER-2 positive breast cancer cells and this finding is in line
with previous studies. Our findings present a probable mechanism of resistance
against paclitaxel chemotherapy in HER2-positive breast cancers.
PMID- 28509577
TI - Alexithymia, suicidal ideation and health-risk behaviours: a survey of Canadian
men.
AB - OBJECTIVE: Restricted emotional abilities may present significant implications
for men's health. The purpose of this study was to examine the relationship
between alexithymia and several health-risk behaviours: substance misuse,
aggressive and risky behaviours and suicidal ideation. METHODS: A nationally
representative sample of 1000 Canadian men responded to a survey containing
measures of alexithymia, maladaptive coping behaviours, suicidal ideation and
depressive symptoms. A series of hierarchical regressions were conducted using
alexithymia as the predictor variable and each health-risk behaviour as the
criterion variable, controlling for depressive symptom severity. RESULTS:
Alexithymia was found to be significantly associated with drug use, alcohol use,
angry/aggressive behaviour and risk-taking behaviour - as well as suicidal
ideation - beyond the effects of depressive symptoms. CONCLUSIONS: The findings
provide evidence for the link between alexithymia and several problematic
behaviours that pose risks to men's health.
PMID- 28509578
TI - The burden of hepatorenal syndrome among commercially insured and Medicare
patients in the United States.
AB - BACKGROUND: This study evaluated the characteristics, healthcare resource
utilization (HCRU), and costs, from the payer perspective, of hepatorenal
syndrome (HRS) patients covered by commercial and Medicare insurance. Mortality
was assessed as a secondary outcome. METHODS: Patients were identified from
claims databases of commercially insured patients (OptumHealth Care Solutions
Inc.) in 1998-2014 and Medicare beneficiaries in 2009-2013 (5% Standard Analytic
Files). At the time of their first inpatient admission ("index date") with an HRS
diagnosis (ICD-9 code 572.4), commercially insured patients must be aged 18-64
and Medicare patients must be aged 65 and older. RESULTS: A total of 784
commercially insured and 1061 Medicare HRS patients met the sample selection
criteria. Patients were disproportionately male (commercial: 63.0%; Medicare:
57.9%) with a mean age of 54.1 among commercially insured and 74.1 among Medicare
patients. Within the first 30 days, the average hospital length of stay (LOS) was
12.3 days among commercially insured and 10.8 days among Medicare patients. Based
on Kaplan-Meier analyses, 36% of commercially insured and 26% of Medicare
patients were readmitted within the next 30 days. During follow-up, many patients
received dialysis (commercial: 33.0%; Medicare: 22.1%) or liver transplant
(commercial: 10.7%; Medicare: 1.6%). Average costs within the 90 day follow-up
were $157,665 for commercially insured and $48,322 for Medicare patients, with
68.3% and 78.3% of the costs incurred within the first 30 days. The primary cost
driver was inpatient visits (commercial: 90.3% of costs; Medicare: 83.1% of
costs), with differences between the populations consistent with lower mortality,
higher dialysis rates, and higher transplant rates (both liver and kidney) among
the commercially insured. Using US population and prevalence statistics, these
results suggest that HRS imposes an annual total direct medical cost burden of
approximately $3.0-$3.8 billion to payers over the period. CONCLUSIONS: HRS
imposes a significant economic burden.
PMID- 28509579
TI - Findings of Cognitive Impairment at High Altitude: Relationships to Acetazolamide
Use and Acute Mountain Sickness.
AB - : Phillips, Lara, Buddha Basnyat, Yuchiao Chang, Erik R. Swenson, and N. Stuart
Harris. Findings of cognitive impairment at high altitude: relationships to
acetazolamide use and acute mountain sickness. High Alt Med Biol. 18:121-127,
2017. OBJECTIVE: Acute mountain sickness (AMS) is defined by patient-reported
symptoms using the Lake Louise Score (LLS), which provides limited insight into
any possible underlying central nervous system (CNS) dysfunction. Some evidence
suggests AMS might coexist with altered neural functioning. Cognitive impairment
(CI) may go undetected unless a sensitive test is applied. Our hypothesis was
that a standardized test for mild CI would provide an objective measure of CNS
dysfunction, which may correlate with the symptoms of AMS and so provide a
potential new tool to better characterize altitude-related CNS dysfunction. We
compared a cognitive screening tool with the LLS to see if it correlated with CNS
dysfunction. METHODS: Adult native English-speaking subjects visiting Himalayan
Rescue Association aid stations in Nepal at 3520 m (11,548 ft) and 4550 m (14,927
ft) were recruited. Subjects were administered the LLS and a slightly modified
version of the environmental Quick mild cognitive impairment screen (eQmci).
Medication use for altitude illness was recorded. Scores were compared using the
Spearman's correlation coefficient. Data also included medication use. RESULTS:
Seventy-nine subjects were enrolled. A cut-off of three or greater was used for
the LLS to diagnose AMS and 67 or less for the eQmci to diagnose CI. There were
22 (28%) subjects who met criteria for AMS and 17 (22%) subjects who met criteria
for CI. There was a weak correlation (r2 = 0.06, p = 0.04) between eQmci score
and LLS. In matched subjects with identical LLS, recent acetazolamide use was
associated with significantly more CI. CONCLUSION: Field assessment of CI using a
rapid standardized tool demonstrated that a substantial number of subjects were
found to have mild CI following rapid ascent to 3520-4550 m (11,548-14,927 ft).
The weak correlation between the LLS and eQmci suggests that AMS does not result
in CI. Use of acetazolamide appears to be associated with CI at all levels of AMS
severity.
PMID- 28509580
TI - Use of minimal residual disease assessment in the treatment of chronic
lymphocytic leukemia.
AB - Progress in chronic lymphocytic leukemia (CLL) therapies has extended greatly the
length and depth of remission, with the goal of treatment advancing towards a
cure for some patients. Accordingly, clinical endpoints must evolve to capture
these outcomes, and to provide faster access to novel therapies. Minimal residual
disease (MRD) is an important endpoint representing more accurately the depth of
remission than complete response (CR), and is highly prognostic of progression
free survival (PFS) and overall survival (OS). MRD could be considered a key
outcome of clinical trials and, as a surrogate for PFS, could identify the most
cost-effective and durable treatment sequencing. MRD testing could also determine
which patients would benefit from additional therapy and, accordingly, ascertain
when therapy should be stopped earlier, to reduce toxicity and increase treatment
free intervals. Our article discusses possible uses of MRD in the modern era of
CLL, including its definition, measurement, and value as a surrogate endpoint in
clinical trials, and its potential roles in clinical practice.
PMID- 28509581
TI - Dexamethasone distribution characteristic following controllable continuous sub
tenon drug delivery in rabbit.
AB - Drug delivery systems are required to be safe, minimally invasive and effectively
delivery drug to the target tissues. But delivery drugs to the eye has not yet
satisfied this need. Here, we focused on examining the distribution of
dexamethasone (DEX) in ocular and plasmic samples following controllable
continuous sub-Tenon drug delivery (CCSDD) of dexamethasone disodium phosphate
(DEXP) in rabbit, and to compare that with two traditional routes:
subconjunctival injection and intravenous injection. The DEX concentration was
analyzed by Shimadzu LC-MS 2010 system. In CCSDD group, during observed 24 h, the
mean DEX level in collected samples from highest to lowest following in order:
sclera, cornea, retina/choroid, iris, plasma, aqueous humor, lens and vitreous
body. In ocular solid tissue, the DEX level in posterior segment is higher than
in anatomic corresponding anterior segment, but it is opposite in ocular fluid
tissue. High levels of DEX were maintained at 12 h in the ocular tissue
immediately after the administration. Even at 24 h, the mean DEX concentration
was 31.72 ng/ml and 22.40 ng/ml in aqueous and vitreous, respectively. In CCSDD
group, the ocular DEX exposure (AUC0-24) is much higher and plasma exposure is
much less than IV group, and it is also similar in SC group except iris. The
amount of DEX levels are markedly increased in ocular tissues but it yield lower
plasma levels indicating reduction of systemic absorption by CCSDD. Thus, CCSDD
is an effective method of delivering DEX into anterior and posterior segment of
the eye.
PMID- 28509583
TI - The Influence of Attachment Styles on Sexual Communication Behavior.
AB - Attachment theory is one of the major theoretical frameworks for understanding
romantic relationships. Attachment styles are formed through interactions with
caregivers and shape an individual's expectations of subsequent interpersonal
relationships. In this study, we examined how attachment styles influence
participants' ability to communicate with their partners about problems in their
sexual relationship. A community sample of 81 couples engaged in two video
recorded discussions, one representing an aspect of the couple's sexual
relationship where the male partner wanted change and the second representing an
aspect of the sexual relationship where the female partner wanted change.
Conversations were then coded, with each person being rated on three positive
communication dimensions (positive affect, offering solutions, and
responsiveness) and three negative communication dimensions (hostility, negative
affect, and unskilled communication behaviors). As predicted, attachment
avoidance was related to more negative and less positive communication for both
the individual and his or her partner. Our observational data did not reveal any
significant effects of attachment anxiety on sexual communication. These results
can be contrasted with findings from self-report studies that do suggest an
anxious attachment adversely impacts sexual communication.
PMID- 28509582
TI - Tariquidar sensitizes multiple myeloma cells to proteasome inhibitors via
reduction of hypoxia-induced P-gp-mediated drug resistance.
AB - Multiple myeloma (MM) presents a poor prognosis and high lethality of patients
due to development of drug resistance. P-glycoprotein (P-gp), a drug-efflux
transporter, is upregulated in MM patients post-chemotherapy and is involved in
the development of drug resistance since many anti-myeloma drugs (including
proteasome inhibitors) are P-gp substrates. Hypoxia develops in the bone marrow
niche during MM progression and has long been linked to chemoresistance.
Additionally, hypoxia-inducible transcription factor (HIF-1alpha) was
demonstrated to directly regulate P-gp expression. We found that in MM patients P
gp expression positively correlated with the hypoxic marker, HIF-1alpha. Hypoxia
increased P-gp protein expression and its efflux capabilities in MM cells in
vitro using flow cytometry. We reported herein that hypoxia-mediated resistance
to carfilzomib and bortezomib in MM cells is due to P-gp activity and was
reversed by tariquidar, a P-gp inhibitor. These results suggest combining
proteasome inhibitors with P-gp inhibition for future clinical studies.
PMID- 28509584
TI - The influence of the crutch setup on stability and weight-bearing parameters in
post total hip replacement surgery patients during quiet standing.
AB - PURPOSE: The purpose of this study is to evaluate the influence of the crutch
setup on standing, in post total hip replacement (THR) surgery patients.
MATERIALS AND METHODS: Thirty patients after THR were randomly assigned to
walking with the elbow flexed (EF) or elbow straight (ES) crutch setup. Subjects
were asked to stand on a force platform in a comfortable position with the crutch
positioned on the unaffected side, facing forward for 10 seconds. Centre of
pressure total path and maximal excursion were evaluated in both medio-lateral
and anterior-posterior planes. Difference in the asymmetry of left/right acromial
height, measured with and without the crutch, was calculated (ACdiff). Percentage
of body weight borne by the crutch (Fcr), symmetry (SIload) between operated and
healthy limbs loading during the trial, together with shoulder forces and moments
were measured. RESULTS: No significant differences between the two groups (p >
.05) were found for stability parameters. ACdiff, Fcr and shoulder load increased
significantly (p < .05) in EF group compared to ES group. In addition leg loading
symmetry was significantly reduced in the EF group. CONCLUSIONS: The present
study showed that the ES setup reduced the force borne by the crutch, the load on
the shoulder joint and it minimized postural and loading asymmetries when
compared to EF setup. Conversely, postural stability was not influenced by the
crutch setup. Implications for Rehabilitation Static posture and weight-bearing
parameters are influenced by crutch setup during quiet standing. Crutch setup
does not influence postural stability. Adjusting the crutch according to the
elbow straight setup reduces the force borne by the crutch and the asymmetry in
lower limbs loading. Forces and moments at the shoulder joint were reduced for
the elbow straight setup group.
PMID- 28509586
TI - Long-term persistent donor-recipient mixed chimerism without disease recurrence
after myeloablative single-unit cord blood transplantation in adult acute myeloid
leukemia following myelodysplastic syndrome.
PMID- 28509585
TI - Identification of a novel fusion TBL1XR1-PDGFRB in a patient with acute myeloid
leukemia harboring the DEK-NUP214 fusion and clinical response to dasatinib.
PMID- 28509587
TI - Link protein N-terminal peptide and fullerol promote matrix production and
decrease degradation enzymes in rabbit annulus cells.
AB - PURPOSE: Intervertebral disc degeneration is a major cause of back pain. Novel
therapies for prevention or reversal of disc degeneration are needed. It is
desirable for potential therapies to target both inflammation and matrix
degeneration. MATERIALS AND METHODS: The combined regenerative potential of link
protein N-terminal peptide (LN) and fullerol on annulus fibrosus (AF) cells was
evaluated in a 3D culture model. RESULTS: Interleukin-1alpha (IL-1alpha)-induced
AF cell degeneration was counteracted by fullerol, LN, and fullerol + LN, with
the latter having the greatest effect on matrix production as evaluated by real
time polymerase chain reaction and glycosaminoglycan assay. IL-1alpha-induced
increases in pro-inflammatory mediators (interleukin-6 and cyclooxygenase-2) and
matrix metalloproteinases (MMP-1, -2, -9, and -13) were also counteracted by
fullerol and LN. CONCLUSION: Our data demonstrate that LN and fullerol
individually, and in combination, promote matrix production and have anti
inflammatory and anti-catabolic effects on AF cells.
PMID- 28509588
TI - PEG-lipid-PLGA hybrid nanoparticles loaded with berberine-phospholipid complex to
facilitate the oral delivery efficiency.
AB - The natural product berberine (BBR), present in various plants, arouses great
interests because of its numerous pharmacological effects. However, the further
development and application of BBR had been hampered by its poor oral
bioavailability. In this work, we report on polymer-lipid hybrid nanoparticles
(PEG-lipid-PLGA NPs) loaded with BBR phospholipid complex using a solvent
evaporation method for enhancing the oral BBR efficiency. The advantage of this
new drug delivery system is that the BBR-soybean phosphatidylcholine complex (BBR
SPC) could be used to enhance the liposolubility of BBR and improve the affinity
with the biodegradable polymer to increase the drug-loading capacity and
controlled/sustained release. The entrapment efficiency of the PEG-lipid-PLGA
NPs/BBR-SPC was observed to approach approximately 89% which is more than 2.4
times compared with that of the PEG-lipid-PLGA NPs/BBR. To the best of our
knowledge, this is the first report on using polymer material for effective
encapsulation of BBR to improve its oral bioavailability. The prepared BBR
delivery systems demonstrated a uniform spherical shape, a well-dispersed core
shell structure and a small particle size (149.6 +/- 5.1 nm). The
crystallographic and thermal analysis has indicated that the BBR dispersed in the
PEG-lipid-PLGA NPs matrix is in an amorphous form. More importantly, the
enhancement in the oral relative bioavailability of the PEG-lipid-PLGA NPs/BBR
SPC was ~343% compared with that of BBR. These positive results demonstrated that
PEG-lipid-PLGA NPs/BBR-SPC may have the potential for facilitating the oral drug
delivery of BBR.
PMID- 28509589
TI - Characteristics and Expression Profile of KRT71 Screened by Suppression
Subtractive Hybridization cDNA Library in Curly Fleece Chinese Tan Sheep.
AB - As an important commercial trait for sheep, curly fleece has a great economic
impact on production costs and efficiency in sheep industry. To identify genes
that are important for curly fleece formation in mammals, a suppression
subtractive hybridization analysis was performed on the shoulder skin tissues
exposed to two different growth stages of Chinese Tan sheep with different
phenotypes (curly fleece and noncurling fleece). BLAST analysis identified 67
differentially expressed genes, of which 31 were expressed lower and 36 were
expressed higher in lambs than in adult sheep. Differential expressions of seven
randomly selected genes were verified using quantitative real-time polymerase
chain reaction (qRT-PCR). KRT71 gene was selected for further study due to its
high correlation with the curly hair phenotype in various mammal species. Semi
qPCR showed distinctively high expression of KRT71 in skin tissues. Moreover,
qPCR result showed a significantly higher expression of KRT71 in curly fleece
than noncurling Tan sheep. The luciferase assay and electrophoresis mobility
shift assay showed that there were transcription factor binding sites in the
promoter region of KRT71 related to the differential expression of KRT71 at the
two growth stages of Tan sheep. Online bioinformation tools predicted MFZ1 as a
transcriptional factor that regulates the expression of KRT71. These studies on
KRT71 gene revealed some mechanisms underlying the relationship between the KRT71
gene and the curly fleece phenotype of Tan sheep.
PMID- 28509590
TI - Health care costs associated with Australian tertiary inflammatory bowel disease
care.
AB - INTRODUCTION: We aimed to describe the total costs of illness for IBD patients
and compare the costs of patients with active disease to those with inactive
disease. MATERIALS AND METHODS: Resource use for IBD management was itemized for
attributable costs (AUD) among all IBD patients over a 12-month period at an
Australian hospital. RESULTS: One hundred and eighty-three patients were included
(87 ulcerative colitis (UC); 93 Crohn's disease (CD); three IBD-unclassified).
The median (IQR) annual overall cost was higher in the CD versus UC group
($15,648 versus $5017; p < .001). The difference in cost between CD and UC was
influenced by the difference in outpatient costs for CD patients $9602 ($4311
$29,805) versus $4867 ($3220-$7249), p < .001). The cost of treating patients
with active disease was $3461 ($1607-$11,771) and was higher in the CD versus the
UC group ($6098 ($2168-$16,471) versus $1638 ($1401-$3767); p = .026) and was
influenced by inpatient admissions. The cost of treating patients in remission
was $2090 ($1552-$12,954) and was higher in the CD versus the UC group [$7977
($1579-$14,304) versus $1848 ($1508-$6601); p = .236]. CONCLUSIONS: There is a
discrepancy in costs of inpatient versus outpatient IBD management and treating
active disease compared with disease in remission. Proactive care may help
prevent disease reaching a severity whereby reactive management of active disease
is required.
PMID- 28509591
TI - Current Practice "Constraints" in the Uptake and Use of Intensive Upper Extremity
Training: A Canadian Perspective.
AB - BACKGROUND: Intensive upper extremity training (IUET) has demonstrated efficacy
in clinical and functioning outcomes in children with hemiplegia. However,
implementation in the clinical context requires novel service models and
knowledge translation. AIMS: To map implementation of IUET in Canada, to identify
factors associated with the implementation and best practices for implementation.
METHODS: Mixed-methods design; descriptive statistics, chi-square tests.
Individual phone interviews and focus groups with purposeful sampling. Thematic
analysis; telephone surveys with managers of 31 pediatric rehabilitation centers
across Canada. Four focus groups across Canada and one in the Netherlands.
RESULTS: Implementation of IUET group interventions is limited in Canada (7/31).
Barriers included beliefs and values related to evidence-based practice,
opportunities for continuing education, researchers-clinicians partnerships,
access to scientific literature, and the presence of a champion. Pressure from
parents and media presenting IUET as a novel and effective therapy, support and
flexibility of families, having the critical mass of clients and a managerial
willingness to accommodate new ideas and restructure service provision were some
facilitators. CONCLUSIONS: Uptake of the evidence requires many steps described
in the knowledge translation cycle. Factors identified in the study could be
considered in most clinical settings to facilitate the uptake of research
evidence for IUET.
PMID- 28509592
TI - Molecular modeling and structure-activity relationships for a series of
benzimidazole derivatives as cruzain inhibitors.
AB - AIM: Chagas disease is endemic in Latin America and no effective treatment is
available. Efforts in drug research have focused on several enzymes from
Trypanosoma cruzi, among which cruzain is a validated pharmacological target.
METHODOLOGY: Chemometric analyses were performed on the data set using the
hologram quantitative structure-activity relationship, comparative molecular
field analysis and comparative molecular similarity index analysis methods.
Docking simulations were executed using the crystallographic structure of cruzain
in complex with a benzimidazole inhibitor. The top-scoring enzyme-inhibitor
complexes were selected for the development of the 3D quantitative structure
activity relationship (QSAR) models and to assess the inhibitor binding modes and
intermolecular interactions. RESULTS: Benzimidazole derivatives as cruzain
inhibitors were used in molecular docking and QSAR studies. Significant
statistical indicators were obtained, and the best models demonstrated high
predictive ability for an external test set (r 2pred = 0.65, 0.94 and 0.82 for
hologram QSAR, comparative molecular field analysis and comparative molecular
similarity index analysis, respectively). Additionally, the graphical information
of the chemometric analyses demonstrated substantial complementarity with the
enzyme-binding site. CONCLUSION: These results demonstrate the relevance of the
QSAR models to guide the design of structurally related benzimidazole derivatives
with improved potency.
PMID- 28509593
TI - Impact of pharmacokinetics on the toxicity and efficacy of clofarabine in
patients with relapsed or refractory acute myeloid leukemia.
AB - Common side effects of clofarabine (CFB) are liver toxicity, particularly a
transient elevation of transaminases and skin toxicity. We studied the
correlation of pharmacokinetic (PK) parameters with these toxicities and the
efficacy of CFB in patients with relapsed or refractory acute myeloid leukemia.
Clofarabine PK parameters showed large inter-individual variability. A higher CFB
area under the curve was significantly associated with higher transaminase levels
(p = .011 for aspartate aminotransferase (AST), adjusted for age, sex, cumulated
CFB dosage, baseline AST, and glomerular filtration rate (GFR)). No significant
association could be found between maximum concentration and the liver toxicity
parameters. The occurrence of skin toxicity and the response to re-induction
chemotherapy evaluated at day 15 were also not associated with PK. In conclusion,
a higher individual CFB exposure is associated with increased liver toxicity
reflected by elevated liver enzymes, without having an impact on anti-leukemic
efficacy.
PMID- 28509594
TI - G-CSF improves safety when you start the day after autologous transplant in
multiple myeloma.
PMID- 28509595
TI - Phase II study of intensified rituximab induction and maintenance for low grade B
cell lymphoma.
AB - Rituximab has markedly improved the outcomes of B cell lymphoma, and its
maintenance has been shown to be beneficial in low grade B cell lymphoma (LGBCL).
We conducted a multicenter, phase II trial of intensive rituximab induction and
maintenance therapy for LGBCL to optimize the rituximab monotherapy. Patients
with newly diagnosed or rituximab naive relapsed LGBCL received 8 weekly
rituximab as induction, then continued maintenance therapy with rituximab for 4
weeks at 6-month intervals. The primary endpoint was the overall response rate
(ORR). Forty-five patients were enrolled from 2005 to 2009 and 36 were eligible.
The ORR was 83.3% (30/36) with a complete response rate of 72.2% (26/36). The 3
year progression-free survival (PFS) was 76.7% with a median follow-up of 43.0
months. Five grade three toxicities were observed (no grade 4). Our findings
suggest that this regimen demonstrates high activity with durable PFS and minimal
toxicity in LGBCL patients.
PMID- 28509596
TI - Joint moment-angle properties of the hip abductors and hip extensors.
AB - PURPOSE: Strengthening of hip joint musculature is common in the rehabilitation
of the lower extremity. However, strength curves for hip abduction and extension
have not been assessed when varying the position of the knee. The force-length
properties of the biarticular muscles can be affected when altering the position
of the knee during the production of hip moments. METHODS: Maximum isometric
joint moments were measured at four different angles of hip abduction and hip
extension, at the two knee positions (0 degrees and 90 degrees ). RESULTS: The
hip abduction and extension moments decreased as the hip moved from an adducted
position and flexed position to an abducted position and extended position,
respectively, resulting in a descending joint moment angle curve for each.
CONCLUSION: The results indicate that position of the knee does not significantly
change the normalized peak hip abduction joint moment, but the position of the
knee does significantly change the normalized peak hip extension joint moment.
This provides a baseline reference of hip joint moment production and can be
utilized when assessing a population with a pathology or prescribing
rehabilitative exercises.
PMID- 28509597
TI - Use of technological aids and interpretation services among children and adults
with hearing loss.
AB - OBJECTIVES: The technological development of communication aids for people with
hearing loss has progressed rapidly over the last decades. Quality has improved
and the number of different types of aids has increased. However, few studies
have examined the prevalence of technology use and interpreting services use
among people with hearing loss as they relate to demographic characteristics of
this population. DESIGN: This study reports from national surveys of children and
adults with hearing loss. Use of hearing aids, cochlear implants, other aids and
interpreting services were analysed with regard to gender, age, degree of hearing
loss, mode of communication, having an additional disability, level of
educational achievement among adults, and whether or not children lived together
with both of their parents. STUDY SAMPLE: 269 children (0-15 years of age) and
839 adults (16-65 years of age). RESULTS: Differences in technology and service
use were associated with age, degree of hearing loss, and mode of communication
among children and adults, and gender and level of educational achievement among
adults. CONCLUSION: Individual and social factors have an impact on technological
hearing aid and interpreter use. More research about individual differences and
clinical implications of support services is needed.
PMID- 28509599
TI - A review of dosimetric and toxicity modeling of proton versus photon craniospinal
irradiation for pediatrics medulloblastoma.
AB - BACKGROUND: Craniospinal irradiation (CSI) is the standard radiation therapy
treatment for medulloblastoma. Conventional CSI photon therapy (Photon-CSI)
delivers significant dose to surrounding normal tissue (NT). Research into
pediatric CSI with proton therapy (Proton-CSI) has increased, with the aim of
exploiting the potential to reduce NT dose and associated post-treatment
complications. This review aims to compare treatment outcomes of pediatric
medulloblastoma patients between Proton- and Photon-CSI treatments. MATERIAL AND
METHODS: A search and review of studies published between 1990 and 2016 comparing
pediatric (2-18 years) medulloblastoma Proton- and Photon-CSI in three aspects -
normal organ sparing and target coverage; normal organ dysfunction and second
malignancy risks - was completed. RESULTS: Fifteen studies were selected for
review and the results were directly compared. Proton-CSI reported improved out
of-field organ sparing while target coverage improvements were inconsistent.
Normal organ dysfunction risks were predicted to be lower following Proton-CSI.
Secondary malignancy risks (SMRs) were generally lower with Proton-CSI based on
several different risk models. CONCLUSIONS: Proton-CSI conferred better treatment
outcomes than Photon-CSI for pediatric medulloblastoma patients. This review
serves to compare the current literature in the absence of long-term data from
prospective studies.
PMID- 28509598
TI - Elevated dopamine D1 receptor availability in striatum of Gottingen minipigs
after electroconvulsive therapy.
AB - Electroconvulsive therapy (ECT), a direct form of brain stimulation, is an
effective antidepressant. We hypothesized that the beneficial effects of ECT are
mediated by increased dopaminergic neurotransmission, in which the baseline
activity of D1 receptors may predict the response to ECT. We established a novel
model of brain stimulation in Gottingen minipigs based on the protocol of ECT
applied in humans. With positron emission tomography (PET), we determined a
measure of dopaminergic neurotransmission with the dopamine D1 receptor
antagonist [11C]SCH23390. Seven minipigs were anesthetized and completed PET at
baseline, prior to the onset of ECT treatment, and at 24-48 h and 8-10 days after
the end of a clinical course of ECT, consisting of 10 ECT sessions over a 3.5
week period. In all pigs, the binding of [11C]SCH23390 to striatal D1 receptors
had increased by 24-48 h after ECT, and in most, binding returned towards
baseline at 8-10 days. Increased binding was observed in inverse proportion to
baseline binding rates. Increased binding to dopamine D1 receptors suggests
facilitation of dopaminergic neurotransmission, which may contribute to the
therapeutic effects of ECT. Importantly, the baseline binding capacity of D1
receptors predicts the magnitude of increased binding, up to a maximum binding
capacity.
PMID- 28509600
TI - How to Pronounce.
PMID- 28509602
TI - A Remote View.
PMID- 28509601
TI - The unattainable criteria for new infant vaccines.
AB - BACKGROUND: In 2013, the US Advisory Committee on Immunization Practices (ACIP)
opted against adding meningococcal vaccines to the infant schedule due to poor
cost-effectiveness. This raises a policy question: if meningococcal disease is
too rare to justify routine vaccination, are there other vaccine-preventable
causes of US infant deaths that could be supported? METHODS: We tabulated US
infant deaths from 2009-2013 using the CDC WONDER database. These causes of death
were then categorized into one of 3 categories: 1) vaccine-preventable using
currently available interventions; 2) potentially vaccine-preventable within the
next 10 years; and 3) not preventable. RESULTS: From 19.8 million births (3.9
million/year), ~122,000 infants died (0.62%). Of these, 181 (0.15% of all deaths)
were preventable using currently available vaccines, while an additional 779 were
categorized as potentially preventable in the next 10 y. By exclusion, 121,040
(99.2%) were judged 'not vaccine-preventable'. Meningococcal deaths contributed
at most 0.03% of all infant deaths, but accounted for 17-34% of current vaccine
preventable deaths. CONCLUSIONS: The low number of vaccine-preventable deaths in
the US makes it increasingly difficult to justify the introduction of any new
infant vaccines.
PMID- 28509603
TI - Reaching Beyond Doing a Survey and a Few Interviews: The Importance of
Maintaining Rigor & Validity in Prehospital Qualitative Research.
PMID- 28509604
TI - Moving forth: Imagining physiotherapy education differently.
AB - Contemporary and future physiotherapists are, and will be, presented with
challenges different to their forebears. Yet, physiotherapy tends to remain tied
to historical ways of seeing the world: these are passed down to generations of
physiotherapy graduates. These historical perspectives privilege particular
knowledge and skills so that students gain competency for graduation. However,
contemporary practice is inherently more complex than the focus on knowledge and
skills would have us believe. Professional life requires students to develop the
capability to deal with uncertain and diverse futures. This paper argues that
physiotherapy needs to think differently about entry-level education; the focus
on knowledge and competencies that has been the mainstay in physiotherapy
education must now be understood in the context of an education that embraces
knowing, doing, being. Two educational frameworks are offered in support of this
argument - threshold concepts and ways of thinking and practicing (WTP). Taken
together, these ideas can assist physiotherapy to think in fresh ways about
disciplinary learning. Threshold concepts and WTP help to understand the nature
of a discipline: its behaviors, culture, discourses, and methods. By
interrogating the discursive aspects of the discipline, physiotherapy educators
will be better placed to provide more relevant preparation for practice.
PMID- 28509605
TI - Safety and immunogenicity of Bio PoxTM, a live varicella vaccine (Oka strain) in
Indian children: A comparative multicentric, randomized phase II/III clinical
trial.
AB - Varicella or chickenpox is a highly contagious disease with a high secondary
attack rate. Almost 30% of Indian adolescents lack protective antibodies against
varicella, emphasizing the need of routine varicella immunization. The Oka VZV is
a well-established, safe and efficacious vaccine strain that is highly
immunogenic and produces lifelong protective immunity. The present multicentric,
open label, randomized, controlled Phase II/III study, compared the Bio PoxTM
(indigenous investigational vaccine) with a licensed vaccine, VarivaxTM [a][a]
Please note that this article refers to the product named VARIVAX as manufactured
by Changchun Keygen Biological Products Ltd., China and marketed in India by VHB
Life Sciences Limited, Mumbai, and not the product VARIVAX(r) owned by Merck
Sharp & Dohme Corp., Rahway, New Jersey, USA. Merck Sharp & Dohme Corp. have
asked us to make clear that the product manufactured by Changchun Keygen
Biological Products Ltd. is unrelated to and is not sponsored, endorsed or
otherwise authorised by Merck Sharp & Dohme Corp. , for its safety and
immunogenicity profile in 252 healthy subjects in the age group of 1-12 y (cohort
I: 6-12 years, II:1-6 years) in 3 tertiary medical institutions. Antibodies were
measured by VZV Glycoprotein Enzyme Linked Immunoassay (IgG ELISA) kit.
Seroconversion percentage in children having pre-vaccination anti VZV IgG titer
<10 mIU/mL (< 5 gp ELISA units/mL) were 80% for Bio PoxTM and 77% for VarivaxTM
(p = 0.692). The seroconversion rate in the group receiving Bio PoxTM was non
inferior to the group that received VarivaxTM. There were mild local reactions
for both the vaccines; none of the patient had fever or required hospitalization
or medication. The Bio PoxTM was found to be safe and immunogenic in children
against VZV infection.
PMID- 28509606
TI - Combined immunotherapy of breast cancer with EGF and VEGF vaccines from DNA
shuffling in a mouse model.
AB - AIM: Development of EGF and VEGF vaccines with high antigenicity for combined
immunotherapy of EGF-EGFR signaling-dependent epithelial tumors such as breast
cancer. METHOD: EGF genes from mouse, human and chicken were randomly assembled
to chimeric genes by DNA shuffling, then a chimeric EGF was selected out by PCR,
SDS-PAGE and immunization for combined immunotherapy of breast cancer with a
previously constructed chimeric VEGF vaccine from shuffling. RESULTS: Combined
vaccination with chimeric EGF and VEGF from shuffling could induce high titer of
antibodies against EGF and VEGF to inhibit tumor growth and angiogenesis, and
improve the survival rate of mice with breast cancer. CONCLUSION: Combined
vaccination with EGF and VEGF from shuffling showed better immunotherapy on EGF
EGFR signaling-dependent epithelial tumors such as breast cancer than the single
agent EGF vaccination.
PMID- 28509607
TI - Intravacc.
PMID- 28509608
TI - Differential diagnosis and recovery of acute bilateral foot drop in a patient
with a history of low back pain: A case report.
AB - BACKGROUND AND PURPOSE: Acute bilateral foot drop is rare and may be due to
peripheral or central lesions. The purpose of this case report was to describe
the differential diagnosis and recovery of a patient with low back pain (LBP)
that awoke with bilateral foot drop. CASE DESCRIPTION: A 39-year-old man with a
history of LBP awoke with a steppage gait pattern. Spinal imaging and tapping
were negative for sinister pathologies. A subsequent history taken by the
physical therapist uncovered that the patient had previously taken a narcotic and
slept in a kneeling position to relieve his LBP. Strength and sensory testing
revealed isolated impairments in the fibular nerve distribution, and bilateral
fibular palsy was suspected and later confirmed with electrophysiological
studies. Surgical fibular nerve decompression was performed, and the patient
underwent physical therapy. OUTCOMES: Five months later the patient demonstrated
antigravity strength and a partial return of sensation. By 17 months, his Lower
Extremity Functional Scale had improved from 17/80 to 78/80, revealing a near
complete recovery. DISCUSSION: The patient's history of LBP was a "red herring"
that delayed the diagnosis and caused undue stress to the patient. This case
stresses the importance of a thorough history and clinical examination.
PMID- 28509610
TI - Development of culture-sensitive clinical teacher evaluation sheet in the
Japanese context.
AB - AIM: Many instruments for evaluating clinical teaching have been developed,
albeit most in Western countries. This study aims to develop a validated cultural
and local context sensitive instrument for clinical teachers in an East Asian
setting (Japan), Japanese Clinical Teacher Evaluation Sheet (JaCTES). METHODS: A
multicenter, cross-sectional evaluation study was conducted. We collected a total
of 1368 questionnaires on 304 clinical teachers, completed by residents in 16
teaching hospitals. The construct validity was examined by conducting a factor
analysis and using structural equation modeling (SEM). We also assessed the
reliability using generalizability analysis and decision study. RESULTS:
Exploratory factor analysis resulted in three-factor (role model, teaching
activities, and accessibility) model including 18 items. Confirmatory factor
analysis was performed, using SEM. The comparative fit index was 0.931 and the
root mean square error of approximation was 0.087, meaning an acceptable goodness
of fit for this model. To obtain a reliable dependability-coefficient of at least
0.70 or higher, 5-8 resident responses are necessary. DISCUSSION AND CONCLUSION:
JaCTES is the first reported instrument with validity evidence of content and
internal structure and high feasibility in Japan, an East Asian setting. Medical
educators should be aware of the local context and cultural aspects in evaluating
clinical teachers.
PMID- 28509609
TI - Amyloid- and FDG-PET in sporadic Creutzfeldt-Jakob disease: Correlation with
pathological prion protein in neuropathology.
AB - INTRODUCTION: The role of positron emission tomography (PET) in Creutzfeldt-Jakob
disease is less defined than in other neurodegenerative diseases. We studied the
correlation between the uptake of 18F-florbetaben and 18F-fluorodeoxyglucose with
pathological prion protein deposition in histopathology in a case. METHODS: A
patient with 80 y old with a rapid neurological deterioration with a confirmed
diagnosis of CJD was studied. PET and MRI studies were performed between 13-20 d
before the death. A region of interest analysis was performed using Statistical
Parametric Mapping. RESULTS: MRI showed atrophy with no other alterations. FDG
PET showed extensive areas of hypometabolism including left frontoparietal lobes
as well as bilateral thalamus. Correlation between uptake of 18F-florbetaben and
pathological prion protein deposition was r = 0.786 (p < 0.05). Otherwise,
correlation between uptake of 18F-FDG and pathological prion protein was r =
0.357 (p = 0.385). Immunohistochemistry with beta-amyloid did not show amyloid
deposition or neuritic plaques. CONCLUSIONS: Our study supports the use of FDG
PET in the assessment of CJD. FDG-PET may be especially useful in cases of
suspected CJD and negative MRI. Furthermore, this case report provides more
evidence about the behavioral of amyloid tracers, and the possibility of a low
affinity binding to other non-amyloid proteins, such as the pathological prion
protein, is discussed.
PMID- 28509611
TI - Efficacy of high-resolution cone-beam CT in the evaluation of perforators in
vertebral artery dissection.
AB - Introduction A major complication of internal coil trapping for vertebral artery
dissection (VAD) is medullary infarction associated with perforator occlusion.
Currently, higher spatial resolution imaging can be obtained with high-resolution
cone-beam computed tomography (VASO CT), and the efficacy of perforator
visualization adjacent to VAD was examined. Methods Eight patients who underwent
internal coil trapping or stent-supported coil embolization underwent VASO CT to
evaluate perforators around VAD. Visualization of perforators was compared with
conventional digital subtraction angiography (DSA) and three-dimensional
rotational angiography (3D-RA). Postoperative MRI was performed in all patients
to investigate ischemic complications. The relationship between the perforators
and the infarction was analyzed. Results Perforator visualization was much
clearer on VASO CT than on 2D DSA or 3D-RA. It was sharp enough to identify each
perforating artery. Medullary infarctions were detected in two cases. In these
two cases, each ischemic lesion corresponded to the territory of a perforator
that was well visualized on VASO CT. The axial view with adjoining tissue
structures on VASO CT was useful to detect the territories of perforators.
Conclusions VASO CT is an efficient modality for the detection and identification
of perforators in the vicinity of VAD. It provides accurate anatomical
information about the vertebrobasilar system that is useful for the treatment of
unruptured VAD.
PMID- 28509612
TI - Defining the phylogenetic position of Amanita species from Andean Colombia.
AB - Amanita is a worldwide-distributed fungal genus, with approximately 600 known
species. Most species within the genus are ectomycorrhizal (ECM), with some
saprotrophic representatives. In this study, we constructed the first
comprehensive phylogeny including ECM species from Colombia collected in native
Quercus humboldtii forests and in introduced Pinus patula plantations. We
included 8 species (A. brunneolocularis, A. colombiana, A. flavoconia, A.
fuligineodisca, A. muscaria, A. rubescens, A. sororcula, and A. xylinivolva) out
of 16 species reported for the country, two new reports: A. citrina and A.
virosa, and a new variety A. brunneolocularis var. pallida. Morphological
taxonomic keys together with a phylogenetic approach using three nuclear gene
regions: partial nuc rDNA 28S nuc rDNA internal transcribed spacers ITS1 and ITS2
and partial translation elongation factor 1-alpha gene (TEF1), were used to
classify the specimens. Several highly supported clades were obtained from the
phylogenetic hypotheses obtained by Bayesian inference and maximum likelihood
approaches, allowing us to position the Colombian collections in a coherent
infrageneric level and to contribute to the knowledge of local Amanita diversity.
PMID- 28509613
TI - Impact of a specialty pharmacy case management service on adherence in patients
receiving oral antineoplastic agents.
AB - Background Patients receiving treatment with oral antineoplastic agents encounter
several barriers to adherence, which may include high medication costs, limited
access to specialty medications, severe adverse effects, complex medication
regimens, and special handling precautions. Medication nonadherence not only
reduces the efficacy of drug therapy but also has the potential to increase
healthcare expenditures due to disease-related hospitalizations. Although several
previous studies have examined patient adherence to oral antineoplastic agents,
few have examined the impact of a specialty pharmacy case management service.
Methods Patient adherence to oral antineoplastic agents was evaluated through a
retrospective analysis of pharmacy claims data and medical chart reviews. The
medication possession ratio (MPR) was used to quantitatively measure adherence
during two 6-month intervals, prior to and following the implementation of a case
management service. Patients with an MPR greater than or equal to 0.8 were
categorized as adherent, while those with an MPR less than 0.8 were categorized
as non-adherent. Results During the first 6-month interval prior to
implementation of the case management service (n = 40), a cumulative average MPR
of 0.922 was observed. Following implementation of the case management service (n
= 56), a non-statistically significant (p = 0.199) increase in MPR to 0.941 was
identified. For patients categorized as non-adherent, a nonstatistically
significant (p = 0.214) decrease from 15% to 7% was identified following the
introduction of the case management service. Conclusion Study results from this
retrospective review indicate that case management services provided through an
outpatient specialty pharmacy may have the potential to improve patient adherence
to oral antineoplastic agents.
PMID- 28509614
TI - The impact of pharmacist telephone calls after discharge on satisfaction of
oncology patients: A randomized controlled study.
AB - Purpose The aim of the study was to determine the impact of telephone follow-up
calls on satisfaction in oncology patients after hospital discharge. Method A
randomized controlled study, in which patients were randomized into two groups:
The experimental group with the telephone follow-up (TFU) calls (intervention)
and the control group (no intervention). The telephone follow-up call was
conducted within 72 h after discharge. During the call, patients were asked about
their medications, namely, whether they received them, understood how to take
them, and whether they developed any medication-related adverse effect. Both
groups were contacted by phone two weeks later to assess their satisfaction with
the discharge medication instructions and the provided pharmaceutical services,
using the 5-point Likert scale. In addition, hospital records were reviewed for
emergency room visits and hospital readmissions within 30 days after discharge.
Results There was no difference in the percentage of patients who reported being
very satisfied between both the intervention and the control groups (45%
intervention vs. 48% control, P = 0.68). The mean time of the intervention phone
call was 3 +/- 1.7 (SD) min. During the telephone follow-up call, medication
related problems were identified in 20% of the patients. There was no significant
difference in emergency room visits and hospital readmissions in the intervention
group vs. control (44% vs. 53%, P = 0.123) and (37% vs. 43%, P = 0.317),
respectively. Conclusion Telephone follow-up calls conducted by a pharmacist to
discharged oncology patients did not improve patients' satisfaction, emergency
room visits or hospital readmissions; however, they helped to identify medication
related adverse effects in the oncology patients.
PMID- 28509615
TI - Mining of a phospholipase D and its application in enzymatic preparation of
phosphatidylserine.
AB - Phosphatidylserine (PS) is useful as the additive in industries for memory
improvement, mood enhancement and drug delivery. Conventionally, PS was extracted
from soybeans, vegetable oils, egg yolk, and biomass; however, their low
availability and high extraction cost were limiting factors. Phospholipase D
(PLD) is a promising tool for enzymatic synthesis of PS due to its
transphosphatidylation activity. In this contribution, a new and uncharacterized
PLD was first obtained from GenBank database via genome mining strategy. The open
reading frame consisted of 1614 bp and potentially encoded a protein of 538-amino
acid with a theoretical molecular mass of 60 kDa. The gene was successfully
cloned and expressed in Escherichia coli. Its enzymatic properties were
experimentally characterized. The temperature and pH optima of PLD were
determined to be 60 degrees C and 7.5, respectively. Its hydrolytic activity was
improved by addition of Ca2+ at 5 mM as compared with the control. The enzyme
displayed suitable transphosphatidylation activity and PS could be synthesized
with L-serine and soybean lecithin as substrates under the catalysis of PLD. This
PLD enzyme might be a potential candidate for industrial applications in PS
production. To the best of our knowledge, this is the first report on genome
mining of PLDs from GenBank database.
PMID- 28509616
TI - Depersonalization, adversity, emotionality, and coping with stressful situations.
AB - Depersonalization is defined as persistent or recurrent episodes of feeling
detached or estranged from a sense of self and the world. This study addressed
the primary question: Do nonclinical individuals who endorse high symptomatic
depersonalization have inherently more intense emotional responses, along with
more childhood adversity and past trauma? In this IRB approved study,
participants who met clinical levels of depersonalization (n = 43, 16.3%) were
compared to a group without clinical levels of depersonalization (n = 221,
83.7%). Adverse childhood experiences, adult traumatic events, emotional
overexcitability, coping strategies under stress, and anxiety were examined in
both groups. The variables to assess depersonalization severity included the
Dissociative Experience Scale-II, Cambridge Depersonalization Scale, and
Multiscale Dissociation Inventory. The results indicated that clinical levels of
depersonalization were identified in 16.3% of the sample. The high
depersonalization group had significantly more adverse childhood experiences, in
particular, emotional abuse and neglect. They also experienced more adult
traumatic events, higher levels of anxiety, more emotional overexcitability, and
they employed a less adaptive emotion-oriented coping strategy under stress. It
is recommended that treating depersonalization symptoms should include examining
childhood adversity, especially emotional abuse and neglect. Based on study
findings, emotion regulation skills should be promoted to help individuals with
elevated depersonalization manage their emotion-oriented coping strategies,
anxiety, and emotional overexcitability.
PMID- 28509617
TI - Intergenerational transmission of traumatization: Theoretical framework and
implications for prevention.
AB - Intergenerational transmission of traumatization (ITT) occurs when traumatized
parents have offspring with increased risk for emotional and behavioral problems.
Although fetal exposure to the maternal biological milieu is known to be one
factor in ITT, PTSD-driven parent-child interactions represent an additional
important and potentially modifiable contributor. The Perinatal Interactional
Model of ITT presented herein proposes that PTSD leads to social learning and
suboptimal parent-child interactions, which undermine child regulatory capacity
and increase distress, largely explaining poor social-emotional outcomes for
offspring of parents with PTSD. Psychosocial intervention, particularly when
delivered early in pregnancy, holds the possibility of disrupting ITT.
PMID- 28509618
TI - Follow-up of patients with thyroglobulin-antibodies: Rising Tg-Ab trend is a risk
factor for recurrence of differentiated thyroid cancer.
AB - PURPOSE: Differentiated thyroid cancer is the most common endocrine malignancy.
Recurrences (5-20%) are the main reason for follow-up. Thyroglobulin (Tg) has
proven to be an excellent disease marker, but thyroglobulin-antibodies (Tg-Ab)
may interfere with Tg measurement, leading to over or underestimation. It is
proposed that the Tg-Ab trend can be used as a marker for disease recurrence, yet
few studies define trend and have a long-term follow-up. The objective of our
study was to investigate the value of a well-defined Tg-Ab trend as a surrogate
marker for disease recurrence during long-term follow-up. METHODS: We
retrospectively studied patients treated at the Nuclear Department of the
University Medical Center Utrecht from 1998 to 2010 and the Netherlands Cancer
Institute from 2000 to 2009. All patients with Tg-Ab 12 months after treatment
were included. The definition of a rise was >50% increase of the Tg-Ab value in a
2 year time period. A decline as >50% decrease of the Tg-Ab value. RESULTS:
Twenty-five patients were included. None of the patients with declining or stable
Tg-Ab without a concomitant rise in Tg developed a recurrence. Four patients did
suffer a recurrence. Three of these patients had a rising Tg-Ab trend, in two of
these patients Tg was undetectable. CONCLUSIONS: Tg-Ab trend can be used as a
crude surrogate marker for long-term follow-up of Tg-Ab patients. A rising trend
in Tg-Ab warrants further investigation to detect recurrent disease. Stable or
declining Tg-Ab levels do not seem to reflect a risk for recurrence.
PMID- 28509620
TI - The role of social workers in addressing nonmedical needs in primary health care.
AB - Nonmedical needs are intricately linked to health. Unaddressed nonmedical needs
often result in poorer health and increased healthcare costs. Although social
workers are well positioned to address nonmedical needs, their role in healthcare
environments to address nonmedical needs is limited. The limited role relates to
a lack of reimbursement streams, which stems from poor articulation about their
unique contributions. An analysis of a case study in which a social worker using
AIMS, a protocolized care coordination model, was undertaken to highlight
specific activities performed by social workers. Implications for patient health
outcomes and healthcare costs are discussed.
PMID- 28509619
TI - Japanese Encephalitis Virus Infection Rate and Detection of Genotype I From Culex
tritaeniorhynchus Collected From Jiangsu, China.
AB - Information regarding the infection rate and genotype shifts for Japanese
encephalitis virus (JEV) are important for JE vaccine application. In Jiangsu
province, China, which is one of the provinces with a high prevalence of JE, JEV
infection in swine and mosquitoes in certain cities has only been investigated in
2008-2009. Lianyungang City has one of the highest numbers of JE cases in Jiangsu
province, and it has a high risk of JEV invasion via migrant birds. JEV infection
in vectors in Lianyungang City, which has urban and rural parts, has not been
investigated. In 2015-2016, we collected mosquitoes in cowsheds with ultraviolet
light traps and detected JEV by reverse transcription-polymerase chain reaction
(RT-PCR) method in Culex tritaeniorhynchus in Xintan village, Xuzhuang village,
and Xiaogaozhuang village in Lianyungang City, China. The proportion of positive
pools, which is calculated by the number of infected pools to the total number of
pools tested in these villages, were 16.67%, 20.00%, and 4.17%, respectively, and
the minimum infection rates, which is calculated as the ratio of the number of
positive pools to the total number of mosquitoes tested, were 3.330/00, 4.000/00,
and 0.830/00, respectively. Four JEV strains from positive samples were coded as
LYG-1, LYG-2, LYG-3, and LYG-4, and the complete E genes were sequenced.
Furthermore, the complete genome of LYG-3 was sequenced. The phylogenetic
analysis indicated that all the four JEV strains belonged to genotype I-b. This
is the first report of genotype I JEV strain in Jiangsu province. The high JEV
infection rate in Culex tritaeniorhynchus indicated a high risk of JE reemergence
in Lianyungang. The detected JEV strains may have similar antigenicity to that of
SA14-14-2 according to molecular characters. These findings suggest that the
vaccine can still be effective in Lianyungang.
PMID- 28509621
TI - Atherosclerotic vascular diseases have really the same risk factors? Comparison
between large abdominal aortic aneurysm and obstructive non-coronary arterial
disease.
AB - Objectives The purpose of this study was to investigate whether there are
differences among clinical conditions and traditional atherosclerotic risk
factors between patients with large abdominal aortic aneurysm and those with
occlusive non-coronary arterial disease. Methods We clinically examined 519
patients with asymptomatic abdominal aortic aneurysm and 672 with severe
obstructive arterial diseases before surgical repair. Results In patients with
abdominal aortic aneurysm, we identified a clear predominance of males ( p <
0.001), more alcohol consumers ( p < 0.05), higher values of diastolic blood
pressure ( p < 0.05), higher values of serum creatinine ( p < 0.005), more
hyperuricemic patients ( p < 0.005) and less diabetics ( p < 0.001). In patients
with occlusive atherosclerotic vasculopathies, we observed more smokers ( p <
0.05), higher systolic blood pressure and more hypertensives ( p < 0.05
respectively) and a prevalence of hypertriglyceridemia ( p < 0.05). Conclusions
Patients with abdominal aortic aneurysm were mostly males with diastolic
hypertension, impaired renal function and less diabetics, while patients with
occlusive arteriopathy were more smokers, hypertensives and more
hypertriglyceridemics.
PMID- 28509622
TI - Attachment insecurity as a mediator of the relationship between childhood trauma
and adult dissociation.
AB - This study aimed to investigate whether attachment insecurity mediates the
relationship between childhood trauma and adult dissociation, specifically with
regard to individual forms of childhood maltreatment. Psychiatric outpatients who
visited a specialized trauma clinic (n = 115) participated in the study. Data
were collected via the Childhood Trauma Questionnaire, Revised Adult Attachment
Scale, and Dissociative Experience Scale. Structural equation modeling and path
analysis were performed to analyze the mediating effects of attachment insecurity
on the relationship between childhood trauma and adult dissociation. Greater
childhood trauma was associated with higher dissociation, and the relationship
between them was fully mediated by attachment anxiety. In path analysis of trauma
subtypes, the effects of emotional abuse, physical abuse, and physical neglect as
a child on adult dissociation were found to be fully mediated by attachment
anxiety. The effect of sexual abuse on dissociation was mediated by a synergistic
effect from both attachment anxiety and attachment avoidance. Regarding emotional
neglect, a countervailing interaction was discovered between the direct and
indirect effects thereof on dissociation; the indirect effect of emotional
neglect on dissociation was partially mediated by attachment insecurity. Specific
aspects of attachment insecurity may help explain the relationships between
individual forms of childhood trauma and adult dissociative symptoms. Tailored
treatments based on affected areas of attachment insecurity may improve outcomes
among patients with dissociative symptoms and a history of childhood trauma.
PMID- 28509623
TI - Gastrostomy in patients with prion disease.
AB - Patients with prion diseases can live for long periods of time in a state of
akinetic mutism given appropriate management of their symptoms. To study symptom
support in these cases, we performed gastrostomies on 3 patients with V180I
genetic Creutzfeldt-Jakob disease (CJD) who had become akinetic and mute, and
compared them to 14 other similar patients being fed by tube. In the 3
gastrostomy cases, there were no direct complications due to the gastrostomy or
tube feeding, nor were there episodes of discontinuation of tube feeding or
initiation of continuous drip infusion due to severe complications. Antibiotics
were administered for mild infections, a complication of CJD, with 0.2% and 8.8%
of the total time after gastrostomy being used for intravenous or transluminal
administration, respectively. We compared the present patient series with that of
our previous report statistically, and found that patients undergoing gastrostomy
required significantly fewer discontinuations of tube feeding than those who did
not. No significant difference in antibiotic administration was found between
groups, however. It is our conclusion that gastrostomy should be allowed for
symptom support in akinetic patients with prion disease, but adequate informed
consent must be provided to the patient's family.
PMID- 28509624
TI - The role of evidence-based therapy relationships on treatment outcome for adults
with trauma: A systematic review.
AB - OBJECTIVE: The purpose of this paper was to systematically review and synthesize
the empirical literature on the effects of evidence-based therapy relationship
(EBR) variables in the psychological treatment for adults who experienced trauma
related distress. METHOD: Studies were identified using comprehensive searches of
PsycINFO, Medline, Published International Literature on Traumatic Stress, and
Cumulative Index to Nursing and Allied Health Literature databases. Included in
the review were articles published between 1980 and 2015, in English that
reported on the impact of EBRs on treatment outcome in clinical samples of adult
trauma survivors. RESULTS: Nineteen unique studies met inclusion criteria. The
bulk of the studies were on therapeutic alliance and the vast majority found that
alliance was predictive of or associated with a reduction in various
symptomotology. Methodological concerns included the use of small sample sizes,
little information on EBRs beyond alliance as well as variability in its
measurement, and non-randomized assignment to treatment conditions or the lack of
a comparison group. CONCLUSIONS: More research is needed on the roles of client
feedback, managing countertransference, and other therapist characteristics on
treatment outcome with trauma survivors. Understanding the role of EBRs in the
treatment of trauma survivors may assist researchers, clinicians, and
psychotherapy educators to improve therapist training as well as client
engagement and retention in treatment.
PMID- 28509626
TI - Custom-compounded bioidentical hormone therapy: why so popular despite potential
harm? The case against routine use.
AB - Wide rejection of conventional hormone therapy (HT) after the initial publication
of the Women's Health Initiative (WHI) led to unjustified use of custom
compounded bioidentical hormones. In the USA, it became an unregulated drug
manufacturer industry in disguise, without proper control and making false claims
and misleading advertisements. Manufacturing quality is not ensured. Unspecific
harm from compounding has occurred on a large scale, such as deaths from infected
products and end-stage renal failure plus carcinoma due to confusion between
different Chinese herbs. Oral estrogens increase venous thromboembolic and
ischemic stroke events, even more when overdosed; these excess risks can be
avoided by non-oral administration, readily accessible in custom-compounded HT by
administering estradiol through diverse routes (of which transdermal is the best
documented). Another risk specific to custom-compounded HT, resulting from
estrogen/progestogen imbalance, might be excess endometrial carcinomas. HT can be
optimized by continuously combining transdermal estradiol with progesterone (when
required). Registered preparations do exist for such a more physiological
treatment and therefore must be preferred. Custom compounding is only seldom
legitimate, for example in case of allergy (such as to peanut oil) or to
prescribe different combinations, doses or components (e.g. estriol,
dehydroepiandrosterone or testosterone), even when not approved by local
regulatory authorities despite being scientifically acceptable.
PMID- 28509625
TI - Direct-Current Stimulation Does Little to Improve the Outcome of Working Memory
Training in Older Adults.
AB - The promise of transcranial direct-current stimulation (tDCS) as a modulator of
cognition has appealed to researchers, media, and the general public. Researchers
have suggested that tDCS may increase effects of cognitive training. In this
study of 123 older adults, we examined the interactive effects of 20 sessions of
anodal tDCS over the left prefrontal cortex (vs. sham tDCS) and simultaneous
working memory training (vs. control training) on change in cognitive abilities.
Stimulation did not modulate gains from pre- to posttest on latent factors of
either trained or untrained tasks in a statistically significant manner. A
supporting meta-analysis ( n = 266), including younger as well as older
individuals, showed that, when combined with training, tDCS was not much more
effective than sham tDCS at changing working memory performance ( g = 0.07, 95%
confidence interval, or CI = [-0.21, 0.34]) and global cognition performance ( g
= -0.01, 95% CI = [-0.29, 0.26]) assessed in the absence of stimulation. These
results question the general usefulness of current tDCS protocols for enhancing
the effects of cognitive training on cognitive ability.
PMID- 28509627
TI - Impact of risk-reducing salpingo-oophorectomy in premenopausal women.
AB - OBJECTIVES: To describe implications of premenopausal risk-reducing salpingo
oophorectomy (RRSO) on quality of life, endocrine symptoms, sexual function,
osteoporosis, cardiovascular health, metabolic syndrome, cognitive impairment and
safety of hormone replacement therapy. METHODS: We searched the following
electronic databases: The Cochrane Library, EMBASE, PsycInfo, and MEDLINE. We
selected controlled and uncontrolled trials of premenopausal women undergoing
RRSO. Two authors independently assessed studies for inclusion. Reference lists
of included reports were searched manually for additional studies. RESULTS:
Surgical menopause leads to more menopausal complaints and sexual dysfunction
than natural menopause. Overall quality of life is not affected by surgery. In
the limited literature, there is no evidence that RRSO leads to more osteopenia
in comparison with natural menopause at a young age. Cohort studies show a slight
impaired cardiovascular health. Cognitive function decreases later in life in
premenopausal oophorectomized women. Short-term hormone replacement therapy seems
to decline postmenopausal complaints and does not seem to increase the risk for
breast carcinoma in mutation carriers without a personal history of breast
carcinoma. CONCLUSIONS: The conclusions of this systematic review are limited by
the absence of randomized, controlled trials. There is growing evidence from
observational studies that RRSO may impact negatively on all-cause non-survival
endpoints.
PMID- 28509628
TI - Impact of the Village Model: Results of a National Survey.
AB - Villages are a relatively new, consumer-directed model that brings together older
adults in a community who have a mutual interest in aging in place. These
membership organizations provide social and civic engagement opportunities,
volunteer provided support services, and referral to vetted community providers
to achieve their primary goals of promoting independence and preventing undesired
relocations. This cross sectional survey of 1,753 active Village members from 28
Villages across the US measured members' perceived impacts in the areas of social
connection, civic engagement, service access, health and well-being, and ability
to age in place. Results showed that involvement in the Village was a key factor
associated with greater perceived impacts. Over half of members perceive that the
Village has improved their sense of connection to others and their feeling that
they have someone to count on. Though younger members in better health were more
likely to perceive impacts in social connections, results suggest older women,
living alone with some disability may be the most likely to experience improved
health, quality of life, and mobility. The implications for social work practice
are discussed.
PMID- 28509629
TI - Nanoparticle-based delivery enhances anti-inflammatory effect of low molecular
weight heparin in experimental ulcerative colitis.
AB - Epithelial administration of low molecular weight heparin (LMWH) has proven its
therapeutic efficiency in ulcerative colitis (UC) but still lacks of a
sufficiently selective drug delivery system. Polymeric nanoparticles were used
here not only to protect LMWH from intestinal degradation but also to provide
targeted delivery to inflamed tissue in experimental colitis mice. LMWH was
associated with polymethacrylate nanoparticles (NP) type A (PEMT-A) or type B
(PEMT-B) of a size: 150 nm resulting in a maximum drug loading: 0.1 mg/mg. In a
lipopolysaccharide-stimulated macrophages both, free LMWH and LMWH-NP have
significantly reduced the cytokines secretion independently from cellular uptake.
The in-vivo therapeutic efficiency was dose dependent as at low doses (100 IU/kg)
only minor differences between free LMWH and LMWH-NP were found and the
superiority of LMWH-NP became prominent with dose increase (500 IU/kg).
Administration of LMWH-NP at 500 IU/kg has markedly improved the clinical
activity as compared to LMWH while similarly pathophysiological indicators
revealed increased therapeutic outcome in presence of NP compared to LMWH alone:
Myeloperoxidase (Colitis control: 10 480 +/- 5335, LMWH-PEMT-A NP: 1507 +/- 2165,
LMWH-PEMT-B NP: 382 +/- 143, LMWH: 8549 +/- 5021 units/g) and tumor necrosis
factor: (Colitis control: 1636 +/- 544, LMWH-PEMT-A NP: 511 +/- 506, LMWH-PEMT-B
NP: 435 +/- 473, LMWH: 1110 +/- 309 pg/g). Associating LMWH with NP is improving
the anti-inflammatory efficiency of LMWH in-vivo by its protection against
degradation in luminal environment and selective drug delivery. Such a
combination holds promise for a highly specific therapy by its double selectivity
towards the inflamed intestinal tissue. LMWH-PEMT NP have significantly improved
the clinical activity in-vivo in comparison to free LMWH.
PMID- 28509630
TI - MRD in AML: a role for detecting leukemic blasts at day 14 post-induction
chemotherapy?
PMID- 28509632
TI - Diagnostic Imaging in Veterinary Dental Practice.
PMID- 28509633
TI - E-mental health and the veterinary profession.
PMID- 28509634
TI - Vitamin D metabolism in canine and feline medicine.
PMID- 28509631
TI - Improving balance, mobility, and dual-task performance in an adolescent with
cerebral palsy: A case report.
AB - BACKGROUND AND PURPOSE: Improving functional mobility is often a desired outcome
for adolescents with cerebral palsy (CP). Traditional neurorehabilitation
approaches are frequently directed at impairments; however, improvements may not
be carried over into functional mobility. The purpose of this case report was to
describe the examination, intervention, and outcomes of a task-oriented physical
therapy intervention program to improve dynamic balance, functional mobility, and
dual-task performance in an adolescent with CP. CASE DESCRIPTION: The participant
was a 15-year-old girl with spastic triplegic CP (Gross Motor Classification
System Level II). Examination procedures included the Canadian Occupational
Performance Measure, 6-minute walk test, Muscle Power Sprint Test, 10 x 5-meter
sprint test, Timed Up and Down Stairs Test, Gross Motor Function Measure,
Gillette Functional Assessment Questionnaire, and functional lower extremity
strength tests. Intervention focused on task-oriented dynamic balance and
mobility tasks that incorporated coordination and speed demands as well as task
specific lower extremity and trunk strengthening activities. Dual task demands
were integrated into all intervention activities. OUTCOMES: Post-intervention
testing revealed improvements in cardiovascular endurance, anaerobic power,
agility, stair climbing, gross motor skills, and mobility. DISCUSSION: The
participant appeared to benefit from a task-oriented program to improve dynamic
balance, functional mobility, and dual-task performance.
PMID- 28509635
TI - Disorders of performance-age bucking bulls.
AB - OBJECTIVE To describe disorders of performance-age bucking bulls. DESIGN
Retrospective case-control study. ANIMALS 78 bucking (cases) and 236 nonbucking
(controls) beef bulls. PROCEDURES The medical record database of a referral
hospital was reviewed to identify beef bulls > 1 year old that were examined for
a medical or musculoskeletal disorder between January 1, 2000, and April 1, 2014.
Bucking bulls were designated as cases, and nonbucking bulls were designated as
controls. For each bull, the signalment, history, physical examination and
diagnostic test results, and clinical diagnosis were recorded. The frequency of
each disorder was compared between cases and controls. RESULTS Fifteen of 78
(19%) cases and 132 of 236 (56%) controls had medical disorders; however, the
frequency did not differ between the 2 groups for any medical disorder.
Musculoskeletal disorders were identified in 55 (70.5%) cases and 109 (46%)
controls. Cases were 10.55 times as likely as controls to have horn and sinus
disorders. Of the 43 (55%) cases examined because of lameness, the thoracic limb
was affected in 19 (44%). Compared with controls, cases were 13.37 and 3.31 times
as likely to have a musculoskeletal disorder of the vertebral region and pelvic
limb, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated bucking
bulls were more likely than nonbucking bulls to develop horn and sinus disorders
and musculoskeletal disorders of the vertebral region and pelvic limbs. The limb
distribution of lameness for bucking bulls may differ from that for nonbucking
bulls.
PMID- 28509636
TI - Letters to the Editor.
PMID- 28509637
TI - Anesthesia Case of the Month.
PMID- 28509638
TI - What Is Your Neurologic Diagnosis?
PMID- 28509639
TI - Factors associated with simulator-assessed laparoscopic surgical skills of
veterinary students.
AB - OBJECTIVE To determine whether simulator-assessed laparoscopic skills of
veterinary students were associated with training level and prior experience
performing nonlaparoscopic veterinary surgery and other activities requiring hand
eye coordination and manual dexterity. DESIGN Experiment. SAMPLE 145 students
without any prior laparoscopic surgical or fundamentals of laparoscopic surgery
(FLS) simulator experience in years 1 (n = 39), 2 (34), 3 (39), and 4 (33) at a
veterinary college. PROCEDURES A questionnaire was used to collect data from
participants regarding experience performing veterinary surgery, playing video
games, and participating in other activities. Participants performed a peg
transfer, pattern cutting, and ligature loop-placement task on an FLS simulator,
and FLS scores were assigned by an observer. Scores were compared among academic
years, and correlations between amounts of veterinary surgical experience and FLS
scores were assessed. A general linear model was used to identify predictors of
FLS scores. RESULTS Participants were predominantly female (75%), right-hand
dominant (92%), and between 20 and 29 years of age (98%). No significant
differences were identified among academic years in FLS scores for individual
tasks or total FLS score. Scores were not significantly associated with prior
surgical or video game experience. Participants reporting no handicraft
experience had significantly lower total FLS scores and FLS scores for task 2
than did participants reporting a lot of handicraft experience. CONCLUSIONS AND
CLINICAL RELEVANCE Prior veterinary surgical and video game experience had no
influence on FLS scores in this group of veterinary students, suggesting that
proficiency of veterinary students in FLS may require specific training.
PMID- 28509641
TI - Seroprevalences of anti-Sarcocystis neurona and anti-Neospora hughesi antibodies
among healthy equids in the United States.
AB - OBJECTIVE To describe the general seroprevalence of anti-Sarcocystis neurona and
anti-Neospora hughesi antibodies among healthy equids by use of indirect
fluorescent antibody tests and determine potential risk factors for
seropositivity. DESIGN Cross-sectional study. SAMPLE Whole blood samples
collected from 5,250 equids (1 sample/animal) across 18 states in the United
States during October 2013. PROCEDURES Information regarding potential risk
factors (geographic region, breed, primary use, sex, and age) was collected along
with the blood samples. For each equid, an indirect fluorescent antibody test was
used to determine serum titers of antibody against each of the 2 protozoal
parasites. Mixed-effects logistic regression models were created to determine ORs
for seropositivity. RESULTS The overall seroprevalence of anti-S neurona and anti
N hughesi antibodies in the tested equids was 78% and 34%, respectively. Of the
equids, 31% were seropositive and 18% were seronegative for antibodies against
both parasites. Factors associated with equids being seropositive for anti-S
neurona antibodies were residence in the South, warmblood breed, and age > 5
years. Seroprevalence of anti-N hughesi antibodies did not differ among equids in
different states across the country, but warmblood breed and age > 5 years were
associated with seropositivity. CONCLUSIONS AND CLINICAL RELEVANCE With regard to
risk factors for S neurona and N hughesi exposure and antibody response among
tested equids, older age was not unexpected; however, the influences of warmblood
breed and geographic location on seropositivity for anti-S neurona antibody but
not for anti-N hughesi antibody deserve further investigation.
PMID- 28509642
TI - Pathology in Practice.
PMID- 28509643
TI - ECG of the Month.
PMID- 28509644
TI - Considerations for extralabel drug use in calves.
PMID- 28509645
TI - What Is Your Diagnosis?
PMID- 28509646
TI - Pathology in Practice.
PMID- 28509649
TI - Advocating for veterinary medicine on the state level.
PMID- 28509648
TI - Video-assisted extirpation of cranial mediastinal masses in dogs: 18 cases (2009
2014).
AB - OBJECTIVE To characterize clinical findings, surgical procedures, complications,
and outcomes in dogs undergoing extirpation of masses from the cranial
mediastinum via video-assisted thoracic surgery (VATS) and establish preliminary
guidelines for case selection when considering VATS for thymectomy in dogs.
DESIGN Retrospective case series. ANIMALS 18 client-owned dogs that underwent
extirpation of a cranial mediastinal mass by means of VATS at 5 academic referral
hospitals from 2009 through 2014. PROCEDURES Medical records were reviewed and
data extracted regarding signalment, clinical signs, physical examination
findings, diagnostic imaging results, surgical approach and duration, cytologic
and histologic examination results, complications, outcome, and cause of death,
when applicable. RESULTS 16 dogs had a thymoma, 1 had thymic anaplastic
carcinoma, and 1 had hemangiosarcoma. Seven had both megaesophagus and myasthenia
gravis. Median approximate tumor volume was 113.1 cm3 (interquartile range, 33.5
to 313.3 cm3). Median duration of VATS was 117.5 minutes (interquartile range,
91.5 to 136.3 minutes). Conversion to an open thoracic surgical procedure was
required for 2 dogs, 1 of which died during surgery. Median survival time
following VATS for dogs with thymoma and concurrent myasthenia gravis and
megaesophagus was 20 days. Dogs with thymoma without paraneoplastic syndrome
survived for >= 60 days, and none of these dogs died of disease-related causes.
CONCLUSIONS AND CLINICAL RELEVANCE VATS appeared to be an acceptable approach for
extirpation of masses from the cranial mediastinum in dogs under certain
conditions. Dogs with myasthenia gravis and megaesophagus had a poor
postoperative outcome.
PMID- 28509650
TI - Update on the use of cyclooxygenase-2-selective nonsteroidal anti-inflammatory
drugs in horses.
AB - Nonsteroidal anti-inflammatory drugs work through inhibition of cyclooxygenase
(COX) and are highly effective for the treatment of pain and inflammation in
horses. There are 2 clinically relevant isoforms of COX. Cyclooxygenase-1 is
constitutively expressed and is considered important for a variety of physiologic
functions, including gastrointestinal homeostasis. Thus, NSAIDs that selectively
inhibit COX-2 while sparing COX-1 may be associated with a lower incidence of
adverse gastrointestinal effects. Various formulations of firocoxib, a COX-2
selective NSAID, labeled for use in horses are available in the United States.
Equine practitioners should know that the FDA limits the use of firocoxib to
formulations labeled for horses, regardless of price concerns. In addition,
practitioners will benefit from understanding the nuances of firocoxib
administration, including the importance of correct dosing and the
contraindications of combining NSAIDs. Together with knowledge of the potential
advantages of COX-2 selectivity, these considerations will help veterinarians
select and treat patients that could benefit from this new class of NSAID.
PMID- 28509651
TI - The concept of immunocompromised district might explain the carcinogenic
progression in hidradenitis suppurativa.
PMID- 28509653
TI - Redefined Boundaries: When Palliative Care Hits Home.
PMID- 28509652
TI - Risk assessment of zinc oxide, a cosmetic ingredient used as a UV filter of
sunscreens.
AB - Zinc oxide (ZnO), an inorganic compound that appears as a white powder, is used
frequently as an ingredient in sunscreens. The aim of this review was to examine
the toxicology and risk assessment of ZnO based upon available published data.
Recent studies on acute, sub-acute, and chronic toxicities of ZnO indicated that
this compound is virtually non-toxic in animal models. However, it was reported
that ZnO nanoparticles (NP) (particle size, 40 nm) induced significant changes in
anemia-related hematologic parameters and mild to moderate pancreatitis in male
and female Sprague-Dawley rats at 536.8 mg/kg/day in a 13-week oral toxicity
study. ZnO displayed no carcinogenic potential, and skin penetration is low. No
observed-adverse-effect level (NOAEL) ZnO was determined to be 268.4 mg/kg/day in
a 13-week oral toxicity study, and a maximum systemic exposure dose (SED) of ZnO
was estimated to be 0.6 mg/kg/day based on topical application of sunscreen
containing ZnO. Subsequently, the lowest margin of safety (MOS) was estimated to
be 448.2, which indicates that the use of ZnO in sunscreen is safe. A risk
assessment was undertaken considering other routes of exposure (inhalation or
oral) and major product types (cream, lotion, spray, and propellant). Human data
revealed that MOS values (7.37 for skin exposure from cream and lotion type; 8.64
for skin exposure of spray type; 12.87 for inhalation exposure of propellant
type; 3.32 for oral exposure of sunscreen) are all within the safe range (MOS >
1). Risk assessment of ZnO indicates that this compound may be used safely in
cosmetic products within the current regulatory limits of 25% in Korea.
PMID- 28509654
TI - Clinical reasoning-embodied meaning-making in physiotherapy.
AB - This article examines physiotherapists' lived experience of practicing
physiotherapy in primary care, focusing on clinical reasoning and decision-making
in the case of a patient we call Eva. The material presented derives from a
larger study involving two women participants, both with a protracted history of
neck and shoulder pain. A total of eight sessions, all of them conducted by the
first author, a professional physiotherapist, in his own practice room, were
videotaped, after which the first author transcribed the sessions and added
reflective notes. One session emerged as particularly stressful for both parties
and is explored in detail in this article. In our analysis, we seek to be
attentive to the experiences of physiotherapy displayed and to explore their
meaning, significance and uniqueness from a phenomenological perspective. Our
research reveals the complexity of integrating multiple theoretical perspectives
of practice in clinical decision-making and suggests that a phenomenological
perspective can provide insights into clinical encounters through its recognition
of embodied knowledge. We argue that good physiotherapy practice demands
tactfulness, sensitivity, and the desire to build a cooperative patient-therapist
relationship. Informed by theoretical and practical knowledge from multiple
disciplines, patient management can evolve and unfold beyond rehearsed routines
and theoretical principles.
PMID- 28509655
TI - Letter from the editor.
PMID- 28509656
TI - Human Vaccines & Immunotherapeutics: News.
PMID- 28509657
TI - The Palliative Care Challenge: Analysis of Barriers and Opportunities to
Integrate Palliative Care in Europe in the View of National Associations.
AB - BACKGROUND: Palliative care (PC) development is diverse and lacks an effective
integration into European healthcare systems. This article investigates levels of
integrated PC in European countries. METHODS: A qualitative survey was undertaken
for the 2013 EAPC Atlas of PC in Europe with boards of national associations,
eliciting opinions on opportunities for, and barriers to, PC development.
ANALYSIS: Barriers and opportunities directly related to PC integration were
identified and analyzed thematically according (1) to the dimensions of the World
Health Organization (WHO) public health model and (2) by the degree of service
provision in each country. A frequency analysis of dimensions and level of
provision was also conducted. RESULTS: In total, 48/53 (91%) European countries
responded to the survey. A total of 43 barriers and 65 opportunities were
identified as being related to PC integration. Main barriers were (1) lack of
basic PC training, with a particular emphasis on the absence of teaching at the
undergraduate level; (2) lack of official certification for professionals; (3)
lack of coordination and continuity of care for users and providers; (4) lack of
PC integration for noncancer patients; (5) absence of PC from countries'
regulatory frameworks; and (6) unequal laws or regulations pertaining to PC
within countries. Innovations in education and new regulatory frameworks were
identified as main opportunities in some European countries, in addition to
opportunities around the implementation of PC in home care, nursing home
settings, and the earlier integration of PC into patients' continuum of care.
With increasing provision of services, more challenges for the integration are
detected (p < 0.005). CONCLUSION: A set of barriers and opportunities to PC
integration has been identified across Europe, by national associations, offering
a barometer against which to check the challenge of integration across countries.
PMID- 28509658
TI - Haemosporidian Parasites of Reptiles and Birds from Gabon, Central Africa.
AB - Haemosporidian parasites are protozoans that infect many different vertebrate
hosts. Re-examination of the diversity of haemosporidian parasites, using
molecular tools, has generally led to rearrangements of traditional
classifications. In this study, we explored the diversity of haemosporidian
parasites infecting some species of reptile and birds living in the forests of
Gabon, Central Africa, by analyzing a collection of 128 samples of reptiles and
birds. We found that samples from 2 tortoise species (Pelusios castaneus and
Kinixys erosa) and 3 bird species (Turtur afer, Ceratogymna atrata, and Agelastes
niger) were infected by Haemocystidium spp. and Parahaemoproteus spp.,
respectively. From an ecological point of view, these lineages of parasites do
not show host specificity because we have found them in several host species (2
tortoise and 3 bird species) that come from different areas of Gabon forest which
are infected with these parasites. Also, our phylogenetic analyses revealed that
the obtained lineages are related to isolates from other continents found in the
same groups of vertebrates. Thus, our results show that haemosporidian parasites
are also infecting central African vertebrates and that new lineages of these
parasites are circulating in wild animals of the Gabon forest.
PMID- 28509659
TI - Reasons for transferring HIV care in London.
AB - People living with HIV in England, as well as non-UK born and individuals without
residency, can access free HIV care at any service in England. We investigated
reasons for transfer of care to three London HIV units by asking all patients
transferring to fill in a questionnaire exploring reasons for leaving their
previous centre and reasons for choosing the new service. A total of 111 patients
completed the questionnaire. The majority of patients transferred from abroad to
London HIV units, compared to within the UK. The main reason for leaving their
current service was location, which was also the main reason for choosing the
service they transferred to. The results of this audit can be used to improve all
services to ensure any concerns patients may have are eliminated and provide
healthcare tailored to patients' needs.
PMID- 28509661
TI - The relationship between interpersonal trauma history and the functions of non
suicidal self-injury in young adults: An experience sampling study.
AB - Non-suicidal self-injury (NSSI) has been reported to serve a range of functions
for individuals who engage in it. Despite considerable variation in NSSI
functions between individuals, limited attention has been paid to exploring
relationships between NSSI functions and other characteristics of self-injuring
individuals, such as trauma history. This is despite allusion to trauma history
in the suggested etiology of some NSSI functions (e.g., anti-dissociation, self
punishment). The present study used a 21-day online daily diary to explore
possible relationships between common NSSI functions and past interpersonal
trauma in community young adults (n = 38). The interpersonal boundaries and anti
dissociation functions significantly related to interpersonal trauma severity in
multiple regression analyses; the interpersonal boundaries function continued to
significantly relate to interpersonal trauma severity when controlling for the
number of NSSI functions endorsed.
PMID- 28509663
TI - Editorial issue 2/2017International journal of psychiatry in clinical practice.
PMID- 28509664
TI - Reliability of the Dissociative Trance Disorder Interview Schedule: A preliminary
report.
AB - One hundred inpatients in a hospital-based Trauma Program in the USA were
interviewed with the Dissociative Trance Disorder Interview Schedule (DTDIS).
There were no significant differences for the DTDIS total score or any of the
subscale scores on test-retest: all t-values comparing the two administrations of
the DTDIS were below 0.7, and all p-values were above 0.5. Cronbach's alpha for
the US sample was 0.966 and for the Israeli sample it was 0.971. The findings
indicate that the DTDIS has good reliability and may be suitable for use in cross
cultural research; however, the results require replication by independent
researchers in a variety of cultures and languages, and in both clinical and
nonclinical samples.
PMID- 28509665
TI - Evaluation of diet pattern and weight gain in postmenopausal women enrolled in
the Women's Health Initiative Observational Study.
AB - It is unclear which of four popular contemporary diet patterns is best for weight
maintenance among postmenopausal women. Four dietary patterns were characterised
among postmenopausal women aged 49-81 years (mean 63.6 (sd 7.4) years) from the
Women's Health Initiative Observational Study: (1) a low-fat diet; (2) a reduced
carbohydrate diet; (3) a Mediterranean-style (Med) diet; and (4) a diet
consistent with the US Department of Agriculture's Dietary Guidelines for
Americans (DGA). Discrete-time hazards models were used to compare the risk of
weight gain (>=10 %) among high adherers of each diet pattern. In adjusted
models, the reduced-carbohydrate diet was inversely related to weight gain (OR
0.71; 95 % CI 0.66, 0.76), whereas the low-fat (OR 1.43; 95 % CI 1.33, 1.54) and
DGA (OR 1.24; 95 % CI 1.15, 1.33) diets were associated with increased risk of
weight gain. By baseline weight status, the reduced-carbohydrate diet was
inversely related to weight gain among women who were normal weight (OR 0.72; 95
% CI 0.63, 0.81), overweight (OR 0.67; 95 % CI 0.59, 0.76) or obese class I (OR
0.63; 95 % CI 0.53, 0.76) at baseline. The low-fat diet was associated with
increased risk of weight gain in women who were normal weight (OR 1.28; 95 % CI
1.13, 1.46), overweight (OR 1.60; 95 % CI 1.40, 1.83), obese class I (OR 1.73; 95
% CI 1.43, 2.09) or obese class II (OR 1.44; 95 % CI 1.08, 1.92) at baseline.
These findings suggest that a low-fat diet may promote weight gain, whereas a
reduced-carbohydrate diet may decrease risk of postmenopausal weight gain.
PMID- 28509668
TI - Norepinephrine in septic shock: when and how much?
AB - PURPOSE OF REVIEW: Norepinephrine is the first-line agent recommended during
resuscitation of septic shock to correct hypotension due to depressed vascular
tone. Important clinical issues are the best timing to start norepinephrine, the
optimal blood pressure target, and the best therapeutic options to face
refractory hypotension when high doses of norepinephrine are required to reach
the target. RECENT FINDINGS: Recent literature has reported benefits of early
administration of norepinephrine because of the following reasons: profound and
durable hypotension is an independent factor of increased mortality, early
administration of norepinephrine increases cardiac output, improves
microcirculation and avoids fluid overload. Recent data are in favor of targeting
a mean arterial pressure of at least 65 mmHg and higher values in case of chronic
hypertension. When hypotension is refractory to norepinephrine, it is recommended
adding vasopressin, which is relatively deficient during sepsis and acts on other
vascular receptors than alpha1-adernergic receptors. However, increasing the dose
of norepinephrine further cannot be discouraged. SUMMARY: Early administration of
norepinephrine is beneficial for septic shock patients to restore organ
perfusion. The mean arterial pressure target should be individualized. Adding
vasopressin is recommended in case of shock refractory to norepinephrine.
PMID- 28509667
TI - Evaluation of hippocampal infolding angle and incomplete hippocampal inversion in
pediatric patients with epilepsy and febrile seizures.
AB - PURPOSE: We aimed to investigate the frequency of incomplete hippocampal
inversion (IHI) and the hippocampal infolding angle (HIA) in pediatric patients
with no additional abnormal findings in the brain. METHODS: Pediatric brain
magnetic resonance imaging (MRI) examinations conducted between September 2012
and February 2015 were screened and 83 patients with epilepsy, 49 patients with
febrile convulsion, and 74 control patients were included in this retrospective
study. Presence of IHI was evaluated and HIA was measured on MRI. RESULTS: IHI
was found in 23 patients in the epilepsy group (27.7%), 15 patients in the
febrile convulsion group (30.6%), and 14 patients in the control group (19.0%),
with no significant difference between the groups (P = 0.27). Compared with the
epilepsy and febrile convulsion groups, HIA was significantly larger in the
control group in sections of the right cerebral pedincule, the left cerebral
pedincule, and the right superior cerebellar pedincule. No correlation was found
between the laterality of the epileptogenic focus in the epilepsy group and
existence of IHI, nor between age and HIA values among the groups. CONCLUSION:
Although IHI is not an uncommon abnormality in the normal pediatric population,
decreased HIA is more frequently found in patients with epilepsy or febrile
convulsions.
PMID- 28509669
TI - Genetic advances in systemic lupus erythematosus: an update.
AB - PURPOSE OF REVIEW: More than 80 susceptibility loci are now reported to show
robust genetic association with systemic lupus erythematosus (SLE). The
differential functional effects of the risk alleles for the majority of these
loci remain to be defined. Here, we review current SLE association findings and
the recent progress in the annotation of noncoding regions of the human genome as
well as the new technologies and statistical methods that can be applied to
further the understanding of SLE genetics. RECENT FINDINGS: Genome-wide
association studies (GWAS) have markedly expanded the catalogue of genetic
signals contributing to SLE development; we can now explain more than 50% of the
disease's heritability. Expression quantitative trait loci mapping with
colocalization analysis of GWAS results help to identify the underlying causal
genes. The Encyclopedia of DNA elements, Roadmap Epigenome, and the Blueprint
Epigenome projects have jointly annotated more than 80% of the noncoding genome,
providing a wealth of information (from healthy individuals) to define the
functional elements within the risk loci. Technologies, such as next-generation
sequencing, chromatin structure determination, and genome editing, will help
elucidate the actual mechanisms that underpin SLE risk alleles. SUMMARY: Gene
expression and epigenetic databases provide a valuable resource to interpret
genetic association in SLE. Expansion of such resources to include disease status
and multiple ancestries will further aid the exploration of the biology
underlying the genetics.
PMID- 28509666
TI - An inhibitory gate for state transition in cortex.
AB - Large scale transitions between active (up) and silent (down) states during quiet
wakefulness or NREM sleep regulate fundamental cortical functions and are known
to involve both excitatory and inhibitory cells. However, if and how inhibition
regulates these activity transitions is unclear. Using fluorescence-targeted
electrophysiological recording and cell-specific optogenetic manipulation in both
anesthetized and non-anesthetized mice, we found that two major classes of
interneurons, the parvalbumin and the somatostatin positive cells, tightly
control both up-to-down and down-to-up state transitions. Inhibitory regulation
of state transition was observed under both natural and optogenetically-evoked
conditions. Moreover, perturbative optogenetic experiments revealed that the
inhibitory control of state transition was interneuron-type specific. Finally,
local manipulation of small ensembles of interneurons affected cortical
populations millimetres away from the modulated region. Together, these results
demonstrate that inhibition potently gates transitions between cortical activity
states, and reveal the cellular mechanisms by which local inhibitory
microcircuits regulate state transitions at the mesoscale.
PMID- 28509670
TI - Pediatric nasal surgery: timing and technique.
AB - PURPOSE OF REVIEW: Timing of pediatric nasal surgery has always been a
controversial topic. Concern over disrupting growing parts of the face and
causing permanent facial deformity has led to a primarily conservative approach.
Many surgeons feel that it is prudent to wait until the patient has completed
nasal growth after puberty to pursue nasal surgery. RECENT FINDINGS: Recently,
this attitude has been challenged with evidence that not only is nasal surgery in
the pediatric age group not a detriment to facial growth, but failure to correct
significant nasal deformity may actually cause dysmorphic facial growth secondary
to obligate mouth breathing. Because of this, recent studies have focused on
determining safe surgical techniques for pediatric nasal surgery, including
inferior turbinate reduction, septoplasty and rhinoplasty. Research focus on this
topic has also been expanded to include quality-of-life measures after nasal
surgery. SUMMARY: Pediatric nasal surgery prior to puberty is not only safe, but
may prevent facial deformity in certain patients.
PMID- 28509671
TI - Complications in facial Mohs defect reconstruction.
AB - PURPOSE OF REVIEW: To review the recent literature in regards to complications
after reconstruction of Mohs defects, outline common pitfalls and to discuss the
literature on avoiding complications as outlined per aesthetic subunit. RECENT
FINDINGS: Complications in facial Mohs reconstruction commonly consist of
infection, wound necrosis and dehiscence, hematoma and suboptimal scarring.
However, site-specific complications such as hairline or eyebrow distortion,
eyelid retraction or ectropion, nasal contour abnormality, alar retraction, nasal
valve compromise, significant facial asymmetry or even oral incompetence must
also be considered. SUMMARY: A successful reconstruction mimics the premorbid
state and maintains function. The use of perioperative antibiotics, sterile
technique, meticulous hemostasis, subcutaneous dissection and deep sutures to
minimize wound tension should be considered for all Mohs reconstructions.
Cartilage grafting can minimize nasal deformity and obstruction. Reconstruction
near the lower eyelid should employ periosteal suspension sutures to minimize
downward tension and lid retraction. Perioral complications, such as microstomia
and oral incompetence, typically improve with time and therapy. Always consider
secondary procedures such as dermabrasion, steroid injection, scar revision and
laser resurfacing to help optimize aesthetic outcome.
PMID- 28509672
TI - Update on injectables in the nose.
AB - PURPOSE OF REVIEW: The use of injectable fillers for nonsurgical rhinoplasty has
increased tremendously over the past decade. This review describes the most
commonly used fillers and their indications in the context of recent reports of
both their successes and failures. RECENT FINDINGS: Hyaluronic acid and calcium
hydroxylapatite are the two most commonly used fillers for injection. Recent
studies have found that most injectable fillers are met with success and patient
satisfaction, but vascular complications are still a serious problem of which
physicians should be wary. SUMMARY: Injectable fillers should continue to be
considered for patients on a case-by-case basis, but physicians should be
knowledgeable of the various filler types, their indications, and injection
technique to prevent serious complications.
PMID- 28509674
TI - Evidence for more intensive cholesterol lowering.
AB - PURPOSE OF REVIEW: In randomized clinical trials, reduction in cardiovascular
disease (CVD) risk with cholesterol-lowering drugs correlates with the LDL
cholesterol decrease. However, because the majority have investigated a fixed
statin dose, current guidelines disagree about the use of statin dose titration
or non-statin adjunctive cholesterol-lowering drugs. RECENT FINDINGS: We
conducted a meta-analysis of all randomized controlled trials with CVD end
points, comparing two intensities of lipid-lowering regimens within the same
population, using varying statins doses and/or potency, ezetimibe or PCSK9
inhibitors and compared the observed number of patients needed to be treated for
10 years to prevent one CVD event (NNT) with NNT predicted from trials of
predominantly single-dose statin.Some 75439 participants in 10 randomized studies
were included. The mean 10-year CVD risk in controls was around 50% and the
incremental mean LDL cholesterol decrease 0.95 mmol/l (36.7 mg/dl). Observed NNT
closely correlated with those predicted from predominantly single-dose statin
trials [18.2 and 17.1; Pearson R=0.844 (P=0.001)]. When pre-treatment LDL
cholesterol exceeded 4 mmol/l (155 mg/dl), achieving a target LDL cholesterol of
1.8 mmol/l (70 mg/dl) was the most effective strategy. At lower pre-treatment
levels, fixed-dose statin equivalent to atorvastatin 80 mg daily was superior.
The target of 40% reduction in non-high density lipoprotein cholesterol was least
effective regardless of pre-treatment LDL cholesterol. SUMMARY: We conclude that
when initial LDL cholesterol exceeds 4 mmol/l and absolute CVD risk demands it, a
target value of 1.8 mmol/l should be achieved, if necessary by adding ezetimibe
and/or PCSK9 inhibitors to statin treatment.
PMID- 28509675
TI - Acute and Long-Term Effects of LVAD Support on Right Ventricular Function in
Children with Pediatric Pulsatile Ventricular Assist Devices.
AB - Right ventricular failure (RVF) is a significant issue when considering left
ventricular assist device (LVAD) implantation in pediatrics. The aim of this
study was to evaluate the effects of LVAD on right ventricular (RV) function in
children. We retrospectively reviewed clinical and echocardiographic data of
children who underwent Berlin Heart EXCOR LVAD focusing on RV function before and
after implantation (1, 3, and 6 month follow-up). An isolated LVAD was used in 27
patients. Median age was 11 months (interquartile range [IQR]: 5-24 months), with
a median weight of 6.3 kg (IQR: 5-9 kg). Median time on ventricular assist device
(VAD) support was 147 days (IQR: 86-210 days). Twenty patients were successfully
bridged to orthotopic heart transplantation (OHT) (74%), six patients died (22%),
and also heart function recovered in one patient (4%). Before LVAD implantation,
nine patients (33%) showed a RV fractional area change (RVFAC) less than or equal
to 30%. After implantation, mean RVFAC increased up until the 3 month follow-up
(43.13%; p = 0.033) and then slightly decreased. In a subgroup of 18 patients,
the average strain value increased after the 1 month follow-up (p = 0.022). Right
ventricular failure developed in 33% of patients before the 1 month follow-up,
and 7.4% experienced RVF at the 6 month follow-up. No patient required
biventricular assist device (BiVAD). In our population, pulsatile-flow LVAD in
children allows optimal RV decompression and function post-LVAD as measured by
improvement in RV function at echo particularly at 1 and 3 month follow-up. At
long-term follow-up, the beneficial effects of LVAD on RV function seem to be
reduced as signs and symptoms of late RVF may develop in some patients despite
LVAD support.
PMID- 28509673
TI - Immune responses to invasive aspergillosis: new understanding and therapeutic
opportunities.
AB - PURPOSE OF REVIEW: Invasive aspergillosis is a worldwide disease that primarily
affects immune-compromised patients, agricultural workers with corneal abrasions,
individuals with structural lung disease, and patients with primary immune
deficiency. The critical function of the immune system is to prevent the
germination of airborne conidia into tissue-invasive hyphae. This review covers
recent advances that shape our understanding of anti-Aspergillus immunity at the
molecular and cellular level. RECENT FINDINGS: Host defense against conidia and
hyphae occurs via distinct molecular mechanisms that involve intracellular and
extracellular killing pathways, as well as cooperation between different myeloid
cell subsets. The strength and efficacy of the host response is shaped by the
tissue microenvironment. In preclinical models of disease, host immune
augmentation strategies have yielded benefits, yet translating these insights
into therapeutic strategies in humans remains challenging. SUMMARY: Although
advances in early diagnostic strategies and in antifungal drugs have ameliorated
clinical outcomes of invasive aspergillosis, further improvements depend on
gaining deeper insight into and translating advances in anti-Aspergillus
immunity.
PMID- 28509676
TI - Isolated Right Ventricular Mechanical Support: Outcomes and Prognosis.
AB - Right ventricular (RV) failure that necessitates isolated mechanical support is
extremely rare. Outcomes have not been described and are limited to case reports.
We sought to evaluate this select group of patients and determine their 30 day
and 1 year survival. We retrospectively reviewed the Mechanical Assist Device
Database at Columbia University from 2007 to 2015. Inclusion criteria consisted
of patients who received isolated RV assist devices (RVADs) without mechanical
support of the left ventricle. We evaluated survival, duration of support,
intensive care unit (ICU) length of stay, and adverse events. There were 55
patients who underwent RVAD placement between February 2007 and April 2015.
Eleven of these patients received isolated RVADs in the absence of mechanical
circulatory support of the left ventricle. Average duration of support was 13.6
days with a median duration of 12 days. Thirty day and 1 year survival was 72.7%
and 54.6%, respectively. This case series is the first to describe 30 day and 1
year outcomes for patients with isolated RV mechanical support. We propose an
interdisciplinary institutional algorithm based on our study population that
maximizes medical therapy and then pursues invasive forms of mechanical support
when end-organ damage persists.
PMID- 28509677
TI - Short article: Stool cytomegalovirus polymerase chain reaction for the diagnosis
of cytomegalovirus-related gastrointestinal disease.
AB - OBJECTIVES: The diagnosis of cytomegalovirus-related gastrointestinal disease
(CMV-GI disease) still requires histopathology, but biopsy is considered
invasive. Stool CMV PCR has been reported in adults as an alternative method to
diagnose this condition; hence, the results between studies are discrepant.
Moreover, no pediatric studies on stool CMV real-time PCR in CMV-GI disease have
been carried out. Here, we evaluate the value of stool CMV real-time PCR in
detecting CMV-GI disease among immunocompromised children. METHODS: We enrolled
immunocompromised patients aged younger than 20 years who presented with
gastrointestinal symptoms at a teaching hospital during January 2015-March 2016.
Stool samples were analyzed for CMV real-time PCR. All patients underwent
esophagogastroduodenoscopy and colonoscopy with mucosal biopsy. RESULTS: We
performed stool CMV real-time PCR in 31 patients, but two could not undergo
endoscopy. Therefore, 29 patients were analyzed. Two additional stool samples
showed inhibitors that interfere with the PCR testing and were precluded from the
final analysis. Among 27 patients, we found CMV-GI disease in seven (26%)
patients. The sensitivity, specificity, and accuracy of stool CMV real-time PCR
were 71, 85, and 82%, respectively. We also found that all patients with CMV-GI
disease had positive plasma CMV real-time PCR (>150 copies/ml). A significant
association between stool and plasma CMV real-time PCR was also noted (P<0.001).
CONCLUSION: Stool CMV real-time PCR may be used as a noninvasive tool in the
diagnosis of CMV-GI disease. Plasma CMV real-time PCR shows a significant
correlation with stool CMV real-time PCR and also represents high diagnostic
values.
PMID- 28509678
TI - Becoming a chef in the human leukocyte antigen kitchen: interpretation and
modification of human leukocyte antigen-antibody assays.
AB - PURPOSE OF REVIEW: Fluorescence-based human leukocyte antigen (HLA) antibody
detection methods, including flow cytometric crossmatch and single antigen bead
assays revolutionized HLA antibody identification and assessment of immunological
risk in transplant candidates and patients. Nevertheless, these assays are not
flawless and their interpretation can be complex. This review highlights the
limitations of the single antigen bead and flow cytometric crossmatch assays and
discusses protocol modifications and interpretive approaches to address these
issues. RECENT FINDINGS: Several limitations of HLA antibody detection methods
have been identified in recent years. Protocol variability, denatured epitopes,
and interfering factors can all significantly impact the identification of
clinically relevant HLA antibodies. A number of solutions to address these
challenges have been developed. These include pretreatment of sera, method
standardization, and protocol modifications. In addition, HLA epitope-based
analysis approaches to improve interpretation of antibody test results have been
introduced. SUMMARY: In the 50 years, since Patel and Terasaki first developed
the crossmatch assay there have been remarkable advances in HLA antibody testing
methodology. However, with these advances, new problems emerged and solutions had
to be developed. As the technology continues to evolve, our methods and ability
to interpret results must keep pace to provide transplant patients with the best
possible care.
PMID- 28509679
TI - The impact of next-generation sequencing in immunogenetics: current status and
future directions.
AB - PURPOSE OF REVIEW: Next-generation sequencing (NGS) has now been established, and
widely recognized, to be the preferred choice for human leukocyte antigen (HLA)
typing. This transformation is based upon the many scientific, operational and
economic benefits this technology affords. In this report, we review the major
advantages, existing limitations and significant promise derived from adopting
this technology in immunogenetics. RECENT FINDINGS: Significant benefits have
emerged from the usage of NGS in a relatively short period, whereby we realize
that this technology not only helps addressing the technical and operational
problems we have had with the legacy methods for HLA typing, but equally
important, it also allows for creative applications in stem cell and organ
transplantation, new ways to investigate associations of the major
histocompatibility complex (MHC) with many diseases and enhance our understanding
regarding the MHC and non-MHC genomic interactions. The emerging picture is one
of significant benefits in the diagnostic sphere of immunogenetics and
transplantation and one of interconnectivity, integrating the many biological
pathways controlled and affected by this unique genomic region. SUMMARY: NGS has
revolutionized the science and practice of immunogenetics. In this article, we
identify the still unresolved issues, the current benefits to transplantation and
the potential for dissecting the complexity of the MHC, one of the most
fascinating regions of the human genome. Using current trends, an attempt is made
to predict future directions and outcomes.
PMID- 28509680
TI - Analyzing Dental Implant Sites From Cone Beam Computed Tomography Scans on a
Tablet Computer: A Comparative Study Between iPad and 3 Display Systems.
AB - PURPOSE: The aim of this study was to compare a medical-grade PACS (picture
archiving and communication system) monitor, a consumer-grade monitor, a laptop
computer, and a tablet computer for linear measurements of height and width for
specific implant sites in the posterior maxilla and mandible, along with
visualization of the associated anatomical structures. MATERIAL AND METHODS: Cone
beam computed tomography (CBCT) scans were evaluated. The images were reviewed
using PACS-LCD monitor, consumer-grade LCD monitor using CB-Works software, a 13"
MacBook Pro, and an iPad 4 using OsiriX DICOM reader software. The operators had
to identify anatomical structures in each display using a 2-point scale. User
experience between PACS and iPad was also evaluated by means of a questionnaire.
RESULTS: The measurements were very similar for each device. P-values were all
greater than 0.05, indicating no significant difference between the monitors for
each measurement. The intraoperator reliability was very high. The user
experience was similar in each category with the most significant difference
regarding the portability where the PACS display received the lowest score and
the iPad received the highest score. CONCLUSIONS: The iPad with retina display
was comparable with the medical-grade monitor, producing similar measurements and
image visualization, and thus providing an inexpensive, portable, and reliable
screen to analyze CBCT images in the operating room during the implant surgery.
PMID- 28509681
TI - Neuroimaging as a tool to study the sources of phenotypic heterogeneity in
Huntington's disease.
AB - PURPOSE OF REVIEW: Huntington's disease is a neurodegenerative disorder
characterized by a triad of motor, cognitive and psychiatric disturbances. There
is great variability regarding the prominence and evolution of each type of
clinical sign. One possible source of phenotypic heterogeneity could be the more
prominent degeneration of specific brain circuits. The scope of this review is to
highlight the most recent neuroimaging studies that have analysed the
relationship between brain changes and motor, cognitive and psychiatric
alterations in Huntington's disease. RECENT FINDINGS: The results from recent
neuroimaging studies are heterogeneous. Although there is a great overlap between
the different regions associated with each symptomatic domain, there is some
degree of differentiation. For example, the motor network is associated with
motor impairment, whereas the ventral striatum is especially involved in
emotional deficits related with psychiatric problems. SUMMARY: Motor, cognitive
and psychiatric impairments are associated with structural and functional brain
biomarkers. However, the specificity of the regions involved remains unknown,
because these studies focused on specific regions and symptoms. In order to tease
apart the neural substrates that underlie the phenotypic heterogeneity in
Huntington's disease, multivariate approaches combining brain and behavioural
measures related to all symptomatic domains should be considered in the future.
PMID- 28509682
TI - New neurosurgical approaches for tremor and Parkinson's disease.
AB - PURPOSE OF REVIEW: The objective of this review is to gather the newest advances
in the surgical treatment of tremor and Parkinson's disease. We will briefly
discuss the potential applications of the new technologies of deep brain
stimulation (DBS), and we will focus on MRI-guided focused ultrasound (MRgFUS).
RECENT FINDINGS: Novel DBS devices are being progressively adopted, particularly
electrodes allowing a longer stimulating surface (suitable for multiple targets
stimulation) and current radial steering (to minimize side effects of
stimulation). New implantable pulse generators are also able to record neurons
and are generating enough knowledge to advance the implementation of adaptive
(closed-loop) DBS.Over the last years, 'minimally-invasive' neurosurgical
approaches for the treatment of movement disorders have been developed: gamma
knife radiosurgery and MRgFUS. Uncontrolled and recent controlled studies have
shown the benefits of MRgFUS targeting the thalamus and pallidus for the
treatment of tremor and Parkinson's disease. SUMMARY: The initial clinical data
are certainly promising and have expanded the current portfolio of neurosurgical
treatments of movement disorders. Many issues are yet to be addressed,
particularly safety of MRgFUS-and how these new treatments compare with the
existing ones.
PMID- 28509683
TI - Conjunctival Squamous Cell Neoplasia Associated With Ocular Cicatricial
Pemphigoid.
AB - The purpose of this study was to describe a possible causal relationship between
ocular cicatricial pemphigoid (OCP) and ocular surface squamous neoplasia. Two
middle-aged female patients with already diagnosed OCP were studied in regard to
the subsequent onset of conjunctival squamous neoplasia. Their clinical
histories, ocular examinations, clinical photographs, and results of biopsies and
any ancillary immunofluorescent laboratory evaluation studies were carefully
reviewed. One patient had a preinvasive squamous dysplasia and the other an
invasive squamous cell carcinoma, both in the unequivocal setting of OCP with
bilateral conjunctivitis, symblephara, and forniceal foreshortening. The patients
had been receiving intensive immunotherapy consisting of some combination of
corticosteroids, rituximab, and interferon alpha. Both patients had a positive
immunofluorescent study demonstrating immunoreactants at the level of the
epithelial basement membrane. Each patient had 2 earlier negative
immunofluorescent studies before a third was positive. While rare, there is 1
previous report of an association between OCP and conjunctival squamous
neoplasia. The current report provides more data supporting the proposal that
this conjunction is more than a random event. Repeat immunofluorescent studies
after an initial negative result in a patient with strong clinical signs of OCP
are imperative due to the frequency of false negative studies in the context of
clinically persuasive disease.
PMID- 28509684
TI - Histone-Complexed DNA Fragments Levels are Associated with Coagulopathy,
Endothelial Cell Damage, and Increased Mortality after Severe Pediatric Trauma.
AB - BACKGROUND: The release of damage-associated molecular pattern molecules in the
extracellular space secondary to injury has been shown to cause systemic
activation of the coagulation system and endothelial cell damage. We hypothesized
that pediatric trauma patients with increased levels of histone-complexed DNA
fragments (hcDNA) would have evidence of coagulopathy and endothelial damage that
would be associated with poor outcomes. METHODS: We conducted a prospective
observational study of 149 pediatric trauma patients and 62 control patients at
two level 1 pediatric trauma centers from 2013 to 2016. Blood samples were
collected upon arrival and at 24 h, analyzed for hcDNA, coagulation
abnormalities, endothelial damage, and clinical outcome. Platelet aggregation was
assessed with impedance aggregometry (Multiplate) and coagulation parameters were
assessed by measuring prothrombin time ratio in plasma and the use of
viscoelastic techniques (Rotational Thromboelastometry) in whole blood. RESULTS:
The median age was 8.3 years, the median injury severity score (ISS) was 20, and
overall mortality was 10%. Significantly higher levels of hcDNA were found on
admission in patients with severe injury (ISS > 25), coagulopathy, and/or
abnormal platelet aggregation. Patients with high hcDNA levels also had
significant elevations in plasma levels of syndecan-1, suggesting damage to the
endothelial glycocalyx. Finally, significantly higher hcDNA levels were found in
non-survivors. CONCLUSION: hcDNA is released following injury and correlates with
coagulopathy, endothelial glycocalyx damage, and poor clinical outcome early
after severe pediatric trauma. These results indicate that hcDNA may play an
important role in development of coagulation abnormalities and endothelial
glycocalyx damage in children following trauma.
PMID- 28509686
TI - Accuracy of Point-of-Care Ultrasonography for Pediatric Ankle Sprain Injuries.
AB - OBJECTIVES: In children with radiograph fracture-negative lateral ankle injuries,
the main objective of this pilot study was to explore the accuracy, sensitivity,
and specificity of point-of-care ultrasound (POCUS) performed by a pediatric
emergency physician in diagnosing anterior talofibular ligament injuries,
radiographically occult distal fibular fractures, and effusions compared with
reference standard magnetic resonance imaging (MRI). METHODS: This was a
prospective cohort pilot study. Children aged 5 to 17 years with an isolated,
acute lateral ankle injury and fracture-negative ankle radiographs were eligible
for enrolment. Within 1 week of the injury, enrolled children returned for MRI
and POCUS of both ankles. RESULTS: Seven children were enrolled, with a mean age
12.1 (SD, 3.0) years. Overall, POCUS agreed with MRI with respect to anterior
talofibular ligament injury in 4 (57%) of 7 cases. Of the 2 cases with MRI
confirmed ligament damage, POCUS accurately identified and graded the extent of
ligament damage in 1 case. Point-of-care ultrasound falsely identified ligament
injuries in 2 cases. Both imaging modalities confirmed the absence of cortical
fractures in all 7 cases. For all findings, POCUS sensitivity and specificity
were 57% and 86%, respectively. CONCLUSIONS: In this pilot study, we established
that POCUS diagnosed the specific pathology of radiograph-negative lateral ankle
injuries with poor sensitivity but good specificity. Thus, POCUS could act as a
tool to exclude significant ligamentous and radiographically occult bony injury
in these cases. A larger study is needed to validate the utility of POCUS for
this common injury.
PMID- 28509685
TI - Modeling Acute Traumatic Hemorrhagic Shock Injury: Challenges and Guidelines for
Preclinical Studies.
AB - Trauma is responsible for a large proportion of the world's burden of disease,
and is by far the biggest killer of young adults. Hemorrhage is the leading cause
of preventable death and its effects are directly correlated with the incidence
multi-organ failure in survivors. Trauma research is challenging due to patient
heterogeneity, limited randomized controlled trials, and in vitro studies that
fail to mimic the systemic injury response. Preclinical research remains
essential for mechanistic and therapeutic discovery. Yet modeling the
multifaceted nature of traumatic injury poses important experimental and welfare
challenges associated with the onset of injury and prehospital and intra
operative care, the limited inter-species validation of coagulation profiles, the
use of anesthesia/analgesia, and its impact on the systemic response to trauma;
and the challenge of sustaining intensive care in recovery models. Proper model
selection depends on the purpose of a given model and the criteria by which the
experimental readouts will be clinically relevant. Such complexity warrants
further refinement of experimental methodology and outcome measures to improve
its clinical efficacy, while ensuring animal well-being. We review the
experimental methodologies currently used for modeling traumatic hemorrhagic
shock and addressing their impact on clinical translation. The aim of the review
is to improve transparency and form a consensus when reporting methodology in
trauma modeling.
PMID- 28509687
TI - Trust in the Medical Profession Among Adolescents in an Emergency Department.
AB - OBJECTIVE: The aims of this study were to assess trust in the medical profession
among adolescents in an urban pediatric emergency department (ED) and explore
factors associated with trust. METHODS: We used a computerized survey to assess
personal trust, perceived trust among family/friends, health care use, general
and genital examination preferences, health behaviors, and demographics among
youth aged 14 to 19 years. The primary outcome was the mean composite score of a
validated 5-item scale. Responses were summed (range, 5-25); higher scores
indicated greater trust. We compared trust between subgroups using the t test for
independent samples. RESULTS: We enrolled 150 adolescents (80% of approached);
146 completed the survey (mean age, 15.6 y; 40% male; 36% African American, 40%
white, 17% Hispanic; 29% commercial insurance). The mean trust score was 19.51 +/
3.1 (range, 7-25), indicating a fairly high level of trust. Trust was not
associated with race, ethnicity, sex, type of insurance, or health care use. The
mean score for those with high paternal trust was higher than those reporting low
paternal trust (19.8 +/- 2.2 vs 15.3 +/- 5.7, P = 0.02); there was no association
with perceived trust among mothers or friends. Preference for a chaperoned
genital examination was associated with lower trust and female sex. CONCLUSIONS:
Adolescents in this ED reported high levels of trust in the medical profession,
and trust was not associated with race, ethnicity, sex, insurance, or health care
use. Youth with lower trust preferred chaperoned genital examinations. Adolescent
trust may be influenced by perceived trust among important adults. Exploration of
these associations seems warranted to facilitate optimal sexual health outcomes.
PMID- 28509688
TI - A prevalence study of thoracic scoliosis in Chilean patients aged 10-20 years
using chest radiographs as a screening tool.
AB - To determine the prevalence of thoracic scoliosis in patients 10-20 years old
using radiographs as a screening tool, we studied 783 patients who obtained chest
radiographs for nonspinal reasons. We measured thoracic curvature in coronal and
sagittal planes; we determined whether age, sex, and sagittal curvature predicted
the coronal curvature. The prevalence of scoliosis was 9.3%: 7.0% had curvatures
10 degrees -20 degrees ; 1.0% had curvatures 20 degrees -30 degrees ; and 1.3%
had curvatures of at least 30 degrees . Females (13%) presented larger prevalence
of scoliosis than males (4.8%) (P<0.01), also with a larger proportion of larger
curvatures. Sex and thoracic kyphosis were independent predictors of the coronal
curvature, age was not.
PMID- 28509689
TI - Risk factors of allopurinol-induced severe cutaneous adverse reactions in a Thai
population.
AB - BACKGROUND: Allopurinol is one of the most common causes of severe cutaneous
adverse drug reactions (SCARs) including drug reactions with eosinophilia and
systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal
necrolysis (TEN). This study identified the risk factors associated with the
development of allopurinol-induced SCARs in a Thai population. PATIENTS AND
METHODS: Eighty-six allopurinol-induced SCARs (i.e. 19 DRESS and 67 SJS/TEN) and
182 allopurinol-tolerant patients were enrolled in the study. The HLA-B*58:01
allele was determined. Clinical and medicinal data were collected. RESULTS:
Results from multivariate analysis showed that only the HLA-B*58:01 and female
sex were identified as risk factors of allopurinol-induced SCARs in this Thai
population. Patients who carried the HLA-B*58:01 allele were at a higher risk of
allopurinol-induced DRESS [odds ratio (OR)=149.2, 95% confidence interval
(CI)=24.0-infinity, P<1.00*10]. Similar results were observed in allopurinol
induced SJS/TEN (OR=175.0, 95% CI=44.3-690.9, P=1.69*10). The risk of allopurinol
induced SCARs in women was higher than that in men (OR=4.6, 95% CI=1.4-15.6,
P=1.44*10). The overall mortality rate of allopurinol-induced SCARs was 11.39%
and a higher mortality rate was observed in elderly women. CONCLUSION: Among the
risk factors identified, the HLA-B*58:01 allele had the greatest impact on the
development of both phenotypes of allopurinol-induced SCARs in this studied Thai
population. In case HLA-B*58:01 genotyping cannot be accessed, close monitoring
of allopurinol usage, especially in elderly women with impaired renal function,
is necessary to reduce the mortality rate of these life-threatening SCARs.
PMID- 28509690
TI - Genetics and its potential to improve type 1 diabetes care.
AB - PURPOSE OF REVIEW: The genetic basis of type 1 diabetes (T1D) is being
characterized through DNA sequence variation and cell type specificity. This
review discusses the current understanding of the genes and variants implicated
in risk of T1D and how genetic information can be used in prediction,
intervention and components of clinical care. RECENT FINDINGS: Fine mapping and
functional studies has provided resolution of the heritable basis of T1D risk,
incorporating novel insights on the dominant role of human leukocyte antigen
(HLA) genes as well as the lesser impact of non-HLA genes. Evaluation of T1D
associated single nucleotide polymorphisms (SNPs), there is enrichment of genetic
effects restricted to specific immune cell types (CD4 and CD8 T cells, CD19 B
cells and CD34 stem cells), suggesting pathways to improved prediction. In
addition, T1D-associated SNPs have been used to generate genetic risk scores
(GRS) as a tool to distinguish T1D from type 2 diabetes (T2D) and to provide
prediagnostic data to target those for autoimmunity screening (e.g. islet
autoantibodies) as a prelude for continuous monitoring and entry into
intervention trials. SUMMARY: Genetic susceptibility accounts for nearly one-half
of the risk for T1D. Although the T1D-associated SNPs in white populations
account for nearly 90% of the genetic risk, with high sensitivity and
specificity, the low prevalence of T1D makes the T1D GRS of limited utility.
However, identifying those with highest genetic risk may permit early and
targeted immune monitoring to diagnose T1D months prior to clinical onset.
PMID- 28509693
TI - Microcirculatory Effects of Botulinum Toxin A in the Rat: Acute and Chronic
Vasodilation.
AB - BACKGROUND: Botulinum toxin-A (BTX) has numerous cosmetic and therapeutic
applications. Our previous studies have found that BTX augments pedicled flap
survival through both vasodilatory effects and attenuation of the inflammatory
response to ischemia in the rat. This study examines the effect of chronic BTX on
microcirculatory vascular tone and its response to acute topical vasodilators in
muscle flaps. METHODS: The spinotrapezius muscle of Sprague-Dawley rats underwent
a single 2-week pretreatment of 0.2 mL saline either with (n = 5) or without (n =
5) 2u BTX. After surgical elevation, an arcade arteriole was observed using a
video caliper device. Vessel diameter was measured at 30-second intervals after
sequential superfusion of nitroglycerin (100 and 200 MUg/mL), multiple
concentrations of lidocaine, and a combination of adenosine (10 MUM) and
nitroprusside (10 MUM) to induce maximum dilation. RESULTS: Baseline and dilation
diameters were expressed as ratios of pharmacologically induced maximum dilation,
whereas percent dilation was defined as the change in diameter over baseline
diameter. We found a significant increase in resting diameter with BTX
pretreatment (P = 0.0028). Compared with the control group, mean baseline
diameter was 15% greater, and percent dilation was 25% less in BTX-pretreated
flaps. There was no significant relationship between BTX pretreatment and
dilation diameter (P = 0.2895) after adjusting for the effect of acute
vasodilators. CONCLUSIONS: Pretreatment with BTX may induce the arteriolar
resting diameter to be closer to their maximum potential diameter. Additionally,
BTX does not display a synergistic effect with topical vasodilators on
vasodilation.
PMID- 28509691
TI - Development of glucose-responsive 'smart' insulin systems.
AB - PURPOSE OF REVIEW: The complexity of modern insulin-based therapy for type I and
type II diabetes mellitus and the risks associated with excursions in blood
glucose concentration (hyperglycemia and hypoglycemia) have motivated the
development of 'smart insulin' technologies (glucose-responsive insulin, GRI).
Such analogs or delivery systems are entities that provide insulin activity
proportional to the glycemic state of the patient without external monitoring by
the patient or healthcare provider. The present review describes the relevant
historical background to modern GRI technologies and highlights three distinct
approaches: coupling of continuous glucose monitoring (CGM) to deliver devices
(algorithm-based 'closed-loop' systems), glucose-responsive polymer encapsulation
of insulin, and molecular modification of insulin itself. RECENT FINDINGS: Recent
advances in GRI research utilizing each of the three approaches are illustrated;
these include newly developed algorithms for CGM-based insulin delivery systems,
glucose-sensitive modifications of existing clinical analogs, newly developed
hypoxia-sensitive polymer matrices, and polymer-encapsulated, stem-cell-derived
pancreatic beta cells. SUMMARY: Although GRI technologies have yet to be
perfected, the recent advances across several scientific disciplines that are
described in this review have provided a path towards their clinical
implementation.
PMID- 28509692
TI - T1D Autoantibodies: room for improvement?
AB - PURPOSE OF REVIEW: Type 1 diabetes (T1D) is now predictable by measuring major
islet autoantibodies (IAbs) against insulin and other pancreatic beta cells
proteins including GAD65 (GADA), islet antigen 2 (IA-2A), and zinc transporter 8
(ZnT8A). The assay technology for IAbs has made great progress; however, several
important aspects still need to be addressed and improved. RECENT FINDINGS:
Currently a radio-binding assay has been well established as the 'gold' standard
assay for all four IAbs. New generation of nonradioactive IAb assay with
electrochemiluminescence technology has been shown to further improve sensitivity
and disease specificity. Recently, multiplexed assays have opened the possibility
of more efficient screening in large populations. Identification of potential new
autoantibodies to neo-antigens or neo-epitopes posttranslational modification is
a new important field to be explored. SUMMARY: Individuals having a single
positive autoantibody are at low risk for progression to T1D, whereas individuals
expressing two or more positive autoantibodies, especially on multiple tests over
time, have nearly 100% risk of developing clinical T1D when followed for over two
decades. More efficient and cost effective IAb assays will hopefully lead to
point-of-care screening in the general population.
PMID- 28509695
TI - A Novel Augmented Reality-Based Navigation System in Perforator Flap
Transplantation - A Feasibility Study.
AB - BACKGROUND: In perforator flap transplantation, dissection of the perforator is
an important but difficult procedure because of the high variability in vascular
anatomy. Preoperative imaging techniques could provide substantial information
about vascular anatomy; however, it cannot provide direct guidance for surgeons
during the operation. In this study, a navigation system (NS) was established to
overlie a vascular map on surgical sites to further provide a direct guide for
perforator flap transplantation. METHODS: The NS was established based on
computed tomographic angiography and augmented reality techniques. A virtual
vascular map was reconstructed according to computed tomographic angiography data
and projected onto real patient images using ARToolKit software. Additionally, a
screw-fixation marker holder was created to facilitate registration. With the use
of a tracking and display system, we conducted the NS on an animal model and
measured the system error on a rapid prototyping model. RESULTS: The NS
assistance allowed for correct identification, as well as a safe and precise
dissection of the perforator. The mean value of the system error was determined
to be 3.474 +/- 1.546 mm. CONCLUSIONS: Augmented reality-based NS can provide
precise navigation information by directly displaying a 3-dimensional individual
anatomical virtual model onto the operative field in real time. It will allow
rapid identification and safe dissection of a perforator in free flap
transplantation surgery.
PMID- 28509694
TI - Does the Use of Acellular Dermal Matrix Increase Postoperative Complications of
the First-Stage Reconstruction of Immediate Expander-Implant Breast
Reconstruction: A Matched Cohort Study.
AB - PURPOSE: Controversy exists regarding complications associated with the use of
acellular dermal matrix (ADM). This likely stems from the heterogeneous and
unmatched patient characteristics in study groups. The purpose of this study was
to analyze complications in a matched cohort to identify whether ADM use
increased postoperative complications of the first-stage immediate expander
implant breast reconstructions. METHODS: A retrospective matched-cohort study was
performed. We retrospectively reviewed prospectively collected data from patients
who underwent immediate expander-implant breast reconstruction after mastectomy
between February 2010 and January 2016. Independent variables included clinical
characteristics, mastectomy weight, mastectomy type, expander size, initial
inflation volume, number of days to drain removal, and adjuvant or neoadjuvant
therapies. Different independent variables between the ADM and non-ADM groups
were used for propensity score matching. After matching, a pairwise comparison of
the 2 cohorts' independent variables was carried out using the Wilcoxon signed
rank test and McNemar test. Incidence of complications was evaluated for the 2
matched cohorts. To adjust for ablative and reconstructive surgeons, a
multivariable generalized estimating equation analysis was performed. RESULTS: A
total of 574 immediate expander-implant breast reconstructions in 533 patients
were included in this study. We identified 398 reconstructions (199 for each
group; ADM and non-ADM group) of matched cohorts using propensity score matching.
Characteristics were similar between the 2 matched cohorts. In the matched
analysis, there were no significant differences in the rate of skin flap
complications (16.1% vs 16.1%, P > 0.999), seroma (4.0% vs 8.5%, P = 0.065),
infection (3.0% vs 3.5%, P = 0.781), and overall complications (21.1% vs 26.1%, P
= 0.251). Acellular dermal matrix was not associated with increased risk of
complication when ablative and reconstructive surgeon factors were considered in
a multivariable analysis (P = 0.511). CONCLUSIONS: A matched cohort analysis
demonstrated that ADM usage is not associated with an increased risk of
complications, including skin flap complications, seroma, and infection. Our
result suggests that ADM can be safely used in immediate expander-implant breast
reconstruction when necessary.
PMID- 28509696
TI - On-Top Index Pollicization After a Partial Amputation of a Syndactylized
Hypoplastic Thumb in a Patient With Townes-Brocks Syndrome.
AB - Townes-Brocks syndrome is a rare autosomal dominant syndrome characterized by
multiple malformations, including thumb anomalies. Thumb hypoplasia poses a
specific problem, where a deficient thumb creates a significant handicap in hand
function. The treatment goal is enabling pinch and grip activity, and the
preferred procedure for a severely hypoplastic thumb is index finger
pollicization. We present a case of on-top index pollicization in a 10-year-old,
after a partial amputation of a previously syndactylized hypoplastic thumb, with
a well-formed first carpometacarpal joint. The decision to proceed with
pollicization was made after considering second toe-to-hand transfer and a
standard pollicization with an amputation of the thumb remnants. Six months after
the procedure, the outcome was evaluated as "good" (19 points) with Percival's
assessment method. The patient uses the operated hand in all activities of daily
life and is doing well in school. This patient's diagnosis of Townes-Brocks
syndrome was confirmed with genetic testing, which gives grounds and incentive to
further investigate other possible related conditions, and provide genetic
counselling and risk assessment. In reconstruction of complex thumb
malformations, especially after previous multiple operations, an individually
tailored reconstruction plan, sometimes involving modifications of standard
reconstructive procedures, is paramount in achieving good results.
PMID- 28509697
TI - Repair of Oropharyngeal Stenosis With Bilateral Buccal Myomucosal Flaps.
AB - Oropharyngeal stenosis (OPS) is a rare postoperative complication of
adenotonsillectomy that can be a source of considerable patient distress and
morbidity. Circumferential scarring of the soft palate and tonsillar pillars
leads to narrowing of the oropharyngeal aperture. This case report describes the
novel use of bilateral buccal myomucosal flaps for the repair of postoperative
OPS in a 20-year-old woman presenting with dysphagia, odynophagia, dyspnea, and
intermittent hypernasal speech. Postoperatively, the patient noted immediate
improvement of her symptoms. At 1-month follow-up, she noted complete resolution
of her symptoms with no dysphagia, nasal regurgitation, speaking difficulty,
dyspnea, or gagging. The buccal flaps were well healed and completely intact,
maintaining appropriate height of the tonsillar pillars. The buccal myomucosal
flap is an effective tool for numerous palatal and oropharyngeal abnormalities
and, as described in this case study, is a reliable, safe, and effective
technique that can be considered for the reconstruction of postsurgical OPS.
PMID- 28509698
TI - A Meta-analysis of Studies Comparing Outcomes of Diverse Acellular Dermal
Matrices for Implant-Based Breast Reconstruction.
AB - BACKGROUND: The current diversity of the available acellular dermal matrix (ADM)
materials for implant-based breast reconstruction raises the issue of whether
there are any differences in postoperative outcomes according to the kind of ADM
used. The present meta-analysis aimed to investigate whether choice of ADM
products can affect outcomes. METHODS: Studies that used multiple kinds of ADM
products for implant-based breast reconstruction and compared outcomes between
them were searched. Outcomes of interest were rates of postoperative
complications: infection, seroma, mastectomy flap necrosis, reconstruction
failure, and overall complications. RESULTS: A total of 17 studies met the
selection criteria. There was only 1 randomized controlled trial, and the other
16 studies had retrospective designs. Comparison of FlexHD, DermaMatrix, and
ready-to-use AlloDerm with freeze-dried AlloDerm was conducted in multiple
studies and could be meta-analyzed, in which 12 studies participated. In the meta
analysis comparing FlexHD and freeze-dried AlloDerm, using the results of 6
studies, both products showed similar pooled risks for all kinds of
complications. When comparing DermaMatrix and freeze-dried AlloDerm with the
results from 4 studies, there were also no differences between the pooled risks
of complications of the two. Similarly, the meta-analysis of 4 studies comparing
ready-to-use and freeze-dried AlloDerm demonstrated that the pooled risks for the
complications did not differ. CONCLUSIONS: This meta-analysis demonstrates that
the 3 recently invented, human cadaveric skin-based products of FlexHD,
DermaMatrix, and ready-to-use AlloDerm have similar risks of complications
compared with those of freeze-dried AlloDerm, which has been used for longer.
However, as most studies had low levels of evidence, further investigations are
needed.
PMID- 28509700
TI - Letter to the Editor: Stopping the Bleeding Is Not Enough.
PMID- 28509699
TI - Penis Transplantation: First US Experience.
AB - OBJECTIVE: We describe the first successful penis transplant in the United States
in a patient with a history of subtotal penectomy for penile cancer. BACKGROUND:
Penis transplantation represents a new paradigm in restoring anatomic appearance,
urine conduit, and sexual function after genitourinary tissue loss. To date, only
2 penis transplants have been performed worldwide. METHODS: After institutional
review board approval, extensive medical, surgical, and radiological evaluations
of the patient were performed. His candidacy was reviewed by a multidisciplinary
team of surgeons, physicians, psychiatrists, social workers, and nurse
coordinators. After appropriate donor identification and recipient induction with
antithymocyte globulin, allograft procurement and recipient preparation took
place concurrently. Anastomoses of the urethra, corpora, cavernosal and dorsal
arteries, dorsal vein, and dorsal nerves were performed, and also inclusion of a
donor skin pedicle as the composite allograft. Maintenance immunosuppression
consisted of mycophenolate mofetil, tacrolimus, and methylprednisolone. RESULTS:
Intraoperative, the allograft had excellent capillary refill and strong Doppler
signals after revascularization. Operative reinterventions on postoperative days
(PODs) 2 and 13 were required for hematoma evacuation and skin eschar
debridement. At 3 weeks, no anastomotic leaks were detected on urethrogram, and
the catheter was removed. Steroid resistant-rejection developed on POD 28 (Banff
I), progressed by POD 32 (Banff III), and required a repeat course of
methylprednisolone and antithymocyte globulin. At 7 months, the patient has
recovered partial sensation of the penile shaft and has spontaneous penile
tumescence. Our patient reports increased overall health satisfaction, dramatic
improvement of self-image, and optimism for the future. CONCLUSIONS: We have
shown that it is feasible to perform penile transplantation with excellent
results. Furthermore, this experience demonstrates that penile transplantation
can be successfully performed with conventional immunosuppression. We propose
that our successful penile transplantation pilot experience represents a proof of
concept for an evolution in reconstructive transplantation.
PMID- 28509701
TI - Educational Gaps in Molecular Diagnostics, Genomics, and Personalized Medicine in
Dermatopathology Training: A Survey of U.S. Dermatopathology Fellowship Program
Directors.
AB - BACKGROUND: Molecular technologies offer clinicians the tools to provide high
quality, cost-effective patient care. We evaluated education focused on molecular
diagnostics, genomics, and personalized medicine in dermatopathology fellowship
training. DESIGN: A 20-question online survey was emailed to all (n = 53)
Accreditation Council for Graduate Medical Education (ACGME)-accredited
dermatopathology training programs in the United States. RESULTS: Thirty-one of
53 program directors responded (response rate = 58%). Molecular training is
undertaken in 74% of responding dermatopathology fellowships, with levels of
instruction varying among dermatology-based and pathology-based programs.
Education differed for dermatology- and pathology-trained fellows in
approximately one-fifth (19%) of programs. Almost half (48%) of responding
program directors believe that fellows are not currently receiving adequate
molecular education, although the majority (97%) expect to incorporate additional
instruction in the next 2-5 years. Factors influencing the incorporation of
relevant education include perceived clinical utility and Accreditation Council
for Graduate Medical Education/residency review committee (RRC) requirements.
Potential benefits of molecular education include increased medical knowledge,
improved patient care, and promotion of effective communication with other
healthcare professionals. More than two-thirds (68%) of responding program
directors believe that instruction in molecular technologies should be required
in dermatopathology fellowship training. CONCLUSIONS: Although all responding
dermatopathology fellowship program directors agreed that molecular education is
important, only a little over half of survey participants believe that their
fellows receive adequate instruction. This represents an important educational
gap. Discussion among those who oversee fellow education is necessary to best
integrate and evaluate teaching of molecular dermatopathology.
PMID- 28509702
TI - Accordion music from the heart: dynamic coronary artery compression.
PMID- 28509703
TI - Pathway for the Management of Atrial Fibrillation and Atrial Flutter.
AB - Atrial fibrillation (AF) is the most common cardiac rhythm disturbance
encountered in clinical practice, and its prevalence is increasing as the
population ages. The American College of Cardiology, the American Heart
Association, and the European Society of Cardiology established guidelines for
the management of patients with AF. Atrial flutter (Afl) is less common and is
often associated with or preceded by AF or occurs in an isolated pattern. A major
limitation of the currently published guidelines for the management of patients
with AF and Afl is their complexity, the fact that official guidelines are
published separately for each of these arrhythmias, and that they were published
several years ago. To address these deficiencies, we have developed a novel
pathway for the management of AF and Afl. The pathway has been designated with
the acronym RACE, which reflects the 4 main components in patient management:
rate control, anticoagulation therapy, cardioversion, and
electrophysiology/antiarrhythmic medication. This pathway is an attempt to
incorporate, in a user-friendly format, the key concepts of the initial diagnosis
and management of these prevalent arrhythmias. This is followed by a
comprehensive guideline for therapy using the RACE acronym.
PMID- 28509704
TI - Effectiveness of 2-hour Troponin in High-risk Patients With Suspected Acute
Coronary Syndrome.
AB - BACKGROUND: Research has shown the safety and effectiveness of drawing a standard
troponin level at presentation and again at 2 hours in only low-risk patients.
Because high-sensitivity troponins are not currently approved in the United
States, we studied the utility of a standard troponin that is presently in use.
Our goal was to determine if 2-hour standard troponin would be safe and effective
in the evaluation of a high-risk cohort of patients never studied previously.
METHODS: We conducted a single-center prospective observational study of adult
patients presenting to the emergency department with signs and symptoms
suggestive of acute coronary syndrome. Patients were defined as high risk if the
attending physician planned to admit or transfer the patient to the observation
unit. History, Electrocardiography, Age, Risk factors, Troponin scores were
calculated on all patients to provide verification that the individuals were high
risk. The primary outcome was a composite of 30-day myocardial infarction, death,
cardiac arrest with return of spontaneous circulation, or dysrhythmia. The
secondary outcome was 30-day revascularization. RESULTS: We included a total of
122 patients with an average follow-up of 112 days (minimum 30 days). A total of
86% of cases had History, Electrocardiography, Age, Risk factors, Troponin scores
>=4. The primary outcome was met in 22 (18%) patients, and the secondary outcome
occurred in 7 (5.7%) patients. The negative predictive value of negative 2-hour
troponins along with no significant delta troponin rise was 98.7%. CONCLUSIONS:
Discharging patients thought to be high risk who have negative troponins at 0 and
2 hours and no delta troponin rise appears safe. No deaths occurred in follow-up.
Larger studies are warranted.
PMID- 28509705
TI - Yield of Cardiac Magnetic Resonance Imaging in Patients With Acute Coronary
Syndrome and No Obstructive Coronary Artery Disease.
AB - PURPOSE: Ten percent to 25% of women and 6%-10% of men with acute coronary
syndrome (ACS) are found to have no obstructive coronary artery disease (CAD) on
coronary computed tomography angiogram or invasive coronary angiography. The
etiology of presentation is often unclear. We examined the diagnostic yield of
cardiac magnetic resonance imaging (CMR) in patients with signs and symptoms
suggestive of an ACS and no obstructive CAD. METHODS: We retrospectively studied
patients with signs and symptoms suggestive of an ACS and no obstructive CAD on
coronary computed tomography angiogram or invasive coronary angiography who had
CMR performed at St. Paul's Hospital, British Columbia, Canada, from 2013 to
2015. No obstructive CAD was defined as <50% stenosis in any epicardial artery.
We compared CMR diagnostic yield in troponin-positive and troponin-negative
patients and determined the etiology of presentation in each category. We also
examined gender differences. RESULTS: Ninety-eight patients met inclusion
criteria. The average age was 55.8 years, 70% were female, and 60% were troponin
positive upon presentation. Abnormal CMR was observed in 35.7% of patients,
yielding a diagnosis in 27.9% of females and 53.5% of males (P = 0.02). Troponin
positive patients had a significantly higher prevalence of an abnormal CMR than
did troponin-negative patients (44.1% vs. 23.1%; P = 0.03). Myocarditis was more
common in troponin-positive patients (25.4% vs. 2.6%; P = 0.002). CONCLUSIONS:
Forty-four percent of patients with positive troponin and with signs and symptoms
suggestive of an ACS, no obstructive CAD on invasive coronary angiography or
coronary computed tomography angiogram, and unclear diagnosis had abnormalities
on CMR that identified the diagnosis. CMR should be considered in patients with
positive troponin values when the etiology for their presentation is unclear.
PMID- 28509706
TI - Length of Stay, Mortality, Cost, and Perceptions of Care Associated With
Transition From an Open to Closed Staffing Model in the Cardiac Intensive Care
Unit.
AB - BACKGROUND: Organizational models in the intensive care unit (ICU) have
classically been described as either closed or open, depending on the presence or
absence of a dedicated ICU team. Although a closed model has been shown to
improve patient outcomes in medical and surgical ICUs, the merits of various care
models have not been previously explored in the cardiac ICU (CICU) setting.
METHODS: From November 2012 to March 2014, data were prospectively collected on
all admissions before and after transition from an open to closed CICU at our
institution. Baseline clinical variables, illness severity, admission and
discharge diagnoses, resource use, and outcomes were recorded. Anonymous surveys
were also collected from nursing and resident trainee participants to evaluate
the influence of unit structure on perceptions of care. Descriptive statistics
were used, and logistic regression modeling was performed to examine the impact
of unit structure on mortality. RESULTS: The study consisted of 670 patients, 332
(49.6%) of whom were admitted to the open CICU model and 338 (50.4%) of whom were
admitted to the closed model. Neither CICU nor hospital mortality differed
between the open and closed units, though length of stay was shorter in the
closed CICU. Additionally, nurses and resident trainees reported that the closed
CICU allowed for better communication, collaboration, and education. CONCLUSIONS:
Although there was no significant impact of unit structure on patient outcomes in
this single-center study, the closed CICU model was associated with better
perceptions of care.
PMID- 28509708
TI - PVCs, PVC-Induced Cardiomyopathy, and the Role of Catheter Ablation.
AB - Premature ventricular contractions (PVCs) are common arrhythmias noticed in the
clinical setting because of premature depolarization of the ventricular myocytes.
Although often thought to be reflective of underlying disease rather than
intrinsically harmful, PVCs have recently been linked with worse outcomes in
patients without significant cardiac disease. Long-term exposure to a high PVC
burden can lead to the development of PVC-induced cardiomyopathy. The
pathogenesis of this condition is poorly understood at the current time. Many
studies have suggested that catheter ablation of these PVCs may result in
reversal of the PVC-induced cardiomyopathy. This article will go over the natural
history of PVCs and PVC-induced cardiomyopathy, as well as review the current
literature on the role of catheter ablation in treating PVC-induced
cardiomyopathy.
PMID- 28509709
TI - Utility of SOFA and Delta-SOFA scores for predicting outcome in critically ill
patients from the emergency department.
AB - OBJECTIVE: The condition of critically ill patients in the emergency department
(ED) varies from moment to moment. The aims of this study are to quantify
sequential organ failure assessment (SOFA) and changes in SOFA scores over time
and determine its prognostic impact. PATIENTS AND METHODS: This is a prospective
observational cohort study. We included 269 patients consecutively admitted to
the ICU from the ED over 18 months. The SOFA scores at ED admission (ED-SOFA) and
ICU admission (ICU-SOFA) were obtained. Relative changes in SOFA scores were
calculated as follows: Delta-SOFA=ICU-SOFA-ED-SOFA. Patients were divided into
two groups depending on the Delta-SOFA score: (a) Delta-SOFA=0-1; and (b) Delta
SOFA more than or equal to 2. RESULTS: The median ED-SOFA score was two points
(interquartile range: 1-4.5) and the Delta-SOFA score was 2 points (interquartile
range: 0-3). The Delta-SOFA score was more powerful (area under the curve: 0.81)
than the ED-SOFA score (area under the curve: 0.75) in predicting hospital
mortality. Sixteen (6%) patients had a Delta-SOFA score less than 0, 116 (43%)
patients had a Delta-SOFA=0-1, and 137 (51%) patients had a Delta-SOFA of at
least 2 points. The probability of being alive at hospital discharge was 51 and
86.5% in Delta-SOFA of at least 2 and Delta-SOFA=0-1 groups, respectively
(P<0.001). Risk factors for an increase of two or more SOFA points were age,
cirrhosis, a diagnosis of sepsis, and a prolonged ED stay. CONCLUSION: SOFA and
changes in the SOFA score over time are potentially useful tools for risk
stratification when applied to critically ill patients admitted to ICUs from the
ED.
PMID- 28509707
TI - Burden of Psychosocial and Cognitive Impairment in Patients With Atrial
Fibrillation.
AB - BACKGROUND: Impairments in psychosocial status and cognition relate to poor
clinical outcomes in patients with atrial fibrillation (AF). However, how often
these conditions co-occur and associations between burden of psychosocial and
cognitive impairment and quality of life (QoL) have not been systematically
examined in patients with AF. METHODS: A total of 218 patients with symptomatic
AF were enrolled in a prospective study of AF and psychosocial factors between
May 2013 and October 2014 at the University of Massachusetts Medical Center.
Cognitive function, depression, and anxiety were assessed at baseline and AF
specific QoL was assessed 6 months after enrollment using validated instruments.
Demographic and clinical information were obtained from a structured interview
and medical record review. RESULTS: The mean age of the study participants was
63.5 +/- 10.2 years, 35% were male, and 81% had paroxysmal AF. Prevalences of
impairment in 1, 2, and 3 psychosocial/cognitive domains (eg, depression,
anxiety, or cognition) were 75 (34.4%), 51 (23.4%), and 16 (7.3%), respectively.
Patients with co-occurring psychosocial/cognitive impairments (eg, >1 domain)
were older, more likely to smoke, had less education, and were more likely to
have heart failure (all P < 0.05). Compared with participants with no
psychosocial/cognitive impairments, AF-specific QoL at 6 months was significantly
poorer among participants with baseline impairment in 2 (B = -13.6, 95% CI: -21.7
to -5.4) or 3 (B = -15.1, 95% CI: -28.0 to -2.2) psychosocial/cognitive domains.
CONCLUSION: Depression, anxiety, and impaired cognition were common in our cohort
of patients with symptomatic AF and often co-occurred. Higher burden of
psychosocial/cognitive impairment was associated with poorer AF-specific QoL.
PMID- 28509710
TI - Ultrasound-guided pericardiocentesis: a novel parasternal approach.
AB - OBJECTIVE: The aim of this study was to evaluate a novel pericardiocentesis
technique using an in-plane parasternal medial-to-lateral approach with the use
of a high-frequency probe in patients with cardiac tamponade. BACKGROUND:
Echocardiography is pivotal in the diagnosis of pericardial effusion and
tamponade physiology. Ultrasound guidance for pericardiocentesis is currently
considered the standard of care. Several approaches have been described recently,
which differ mainly on the site of puncture (subxiphoid, apical, or parasternal).
Although they share the use of low-frequency probes, there is absence of complete
control of needle trajectory and real-time needle visualization. An in-plane and
real-time technique has only been described anecdotally. METHODS AND RESULTS: A
retrospective analysis of 11 patients (63% men, mean age: 37.7+/-21.2 years)
presenting with cardiac tamponade admitted to the tertiary-care emergency
department and treated with parasternal medial-to-lateral in-plane
pericardiocentesis was carried out. The underlying causes of cardiac tamponade
were different among the population. All the pericardiocentesis were successfully
performed in the emergency department, without complications, relieving the
hemodynamic instability. The mean time taken to perform the eight-step procedure
was 309+/-76.4 s, with no procedure-related complications. CONCLUSION: The
parasternal medial-to-lateral in-plane pericardiocentesis is a new technique
theoretically free of complications and it enables real-time monitoring of needle
trajectory. For the first time, a pericardiocentesis approach with a medial-to
lateral needle trajectory and real-time, in-plane, needle visualization was
performed in a tamponade patient population.
PMID- 28509711
TI - Trends in governance structure and activities among not-for-profit U.S.
hospitals: 2009-2015.
AB - BACKGROUND: In U.S. hospitals, boards of directors (BODs) have numerous
governance responsibilities including overseeing hospital activities and guiding
strategic decisions. BODs can help hospitals adapt to changes in their markets
including those stemming from a shift from fee-for-service to value-based
purchasing. The recent increase in market turbulence for hospitals has brought
renewed attention to the work of BODs. PURPOSE: The aim of the study was to
examine trends in hospital BOD structure and activities and determine whether
these changes are commensurate with approaches designed to respond to market
pressures. METHODOLOGY/APPROACH: We examined hospital level data from The
Governance Institute Survey (2009, 2011, 2013, and 2015) and corresponding years
of the American Hospital Association Annual Survey in a pooled, cross-sectional
design. We conducted individual multivariate models with adjustments for hospital
and market characteristics, comparing the changes in BOD structures,
demographics, and activities over time. FINDINGS: The sample included 1,811
hospital-year observations, including 682 unique facilities. We found that BODs
in 2015 had less internal management (beta = -2.25, p < .001) and fewer employed
and nonemployed physicians (beta = -8.28, p < .001) involved on the BOD.
Moreover, compared to 2009, racial and ethnic minorities (2013 beta = 2.88, p <
.001) and women (2013 beta = 1.60, p = .045; 2015 beta = 2.06, p = .049) on BODs
increased over time. In addition, BODs were significantly less likely to spend
time on the following activities in 2015, as compared to 2009: discussing
strategy and setting policy (beta = -5.46, p = .002); receiving reports from
management, board committees, and subsidiaries (beta = -29.04, p < .001); and
educating board members (beta = -4.21, p < .001). Finally, BODs had no changes in
the type of committees reported over time. PRACTICE IMPLICATIONS: Our results
indicate that hospital BODs deploy various strategies to adapt to current market
trends. Hospital decision-makers should be aware of the potential effects of
board structure on organization's position in the changing health care market.
PMID- 28509712
TI - Accelerating access and scale-up of optimized ART in low-income and middle-income
countries: a call for a coordinated end-to-end approach.
AB - PURPOSE OF REVIEW: To discuss how aligning the collective power of scientists,
regulators, drug companies, donors, implementers and advocates to achieve a
single goal - accelerating access to simpler, safer, more robust and more
affordable HIV treatment - can rapidly advance antiretroviral optimization
efforts and enable scale-up. RECENT FINDINGS: Harmonization of traditionally
sequential processes can address the delays commonly experienced in introducing
new products to low-income and middle-income countries, by facilitating an 'end
to-end' approach that mitigates risk and encourages early planning for all
aspects of product introduction. SUMMARY: Planning with the 'end-in-mind' can
facilitate healthy markets, benefit the application of new technologies, and
accelerate the development of improved products in parallel (versus traditionally
sequential efforts).
PMID- 28509714
TI - Preventing Occupational Skin Disease: A Review of Training Programs.
AB - Occupational contact dermatitis (OCD) is a common occupational disease that
impacts a variety of worker groups. Skin protection and disease prevention
training programs have shown promise for improving prevention practices and
reducing the incidence of OCD. This review details the features of training
programs for primary prevention of OCD and identifies gaps in the literature.
Twelve studies were identified for in-depth review: many studies included wet
workers employed in health care, hairdressing, cleaning, and food preparation; 1
program featured manufacturing workers. Few programs provided content on allergic
contact dermatitis, and only 1 was evaluated for long-term effectiveness.
Effective programs were similar in content, delivery method, and timing and were
characterized by industry specificity, multimodal learning, participatory
elements, skin care resource provision, repeated sessions, and management
engagement. Long-term effectiveness, generalizability beyond OCD, workplace
health and safety culture impact, and translation of programs in the North
American context represent areas for future research.
PMID- 28509715
TI - Epidemic of Isothiazolinone Allergy in North America: Prevalence Data From the
North American Contact Dermatitis Group, 2013-2014.
AB - BACKGROUND: Preservative sensitivity patterns evolve with changing use patterns
in products. During the last decade, the use of methylisothiazolinone (MI) at
higher concentrations in both leave-on and rinse-off products has significantly
increased. This is the first North American Contact Dermatitis Group reporting
cycle that includes both methylchloroisothiazolinone (MCI)/MI and MI data.
OBJECTIVE: The aim of this study was to report the prevalence of isothiazolinone
allergy (MCI/MI and MI) in the North American Contact Dermatitis Group patch-test
population from January 1, 2013, to December 31, 2014. METHODS: At 13 centers in
North America, 4860 patients were patch tested in a standardized manner with a
series of 70 allergens, including MCI/MI 0.01% aqueous (aq) and MI 0.2% aq.
RESULTS: Three hundred five patients (6.3%) had a positive reaction to MCI/MI;
this is a significant increase from the previous cycle (5.0%, 2011-2012; P =
0.011). Five hundred twenty-one patients (10.7%) had a positive reaction to MI.
These 2 isothiazolinones were among the most common preservative allergens in the
2013 to 2014 cycle; 11.9% of patch-tested individuals were allergic to 1 or both
isothiazolinones. Individuals with MCI/MI and MI allergy were significantly more
likely to have occupationally related skin disease (P < 0.0001) and hand
dermatitis (P < 0.0001, P = 0.0474). CONCLUSIONS: The epidemic of isothiazolinone
sensitivity documented in Europe is now in North America. Patch testing with only
MCI/MI 0.01% aq will miss approximately half of isothiazolinone allergy cases,
whereas testing with only MI 0.2% aq will miss approximately 10% of
isothiazolinone allergy cases.
PMID- 28509716
TI - Multicenter Patch Testing With Methylchloroisothizoline/Methylisothiazolinone in
100 and 200 ppm Within the International Contact Dermatitis Research Group.
AB - BACKGROUND: The preservative methylchloroisothiazolinone/methylisothiazolinone
(MCI/MI) is a well-known contact sensitizer. Historically, there have been
different opinions on the optimal patch test concentration of MCI/MI, and both
0.01% and 0.02% aqueous (aq.) have been proposed. In 2011, based on literature
reviews, it was recommended that the concentration of 0.02% aq. should be used in
the international baseline series. OBJECTIVES: The aim of this study was to
verify the recommendation from 2011 by comparing the patch test results from
consecutive patch testing with MCI/MI 0.01% and 0.02% in clinics representing
countries around the world. PATIENTS AND METHODS: Two thousand seven hundred
three consecutive patients with dermatitis in 8 dermatology clinics representing
8 countries were patch tested with MCI/MI 0.01% aq. and, in parallel with MCI/MI
0.02% aq., provisionally included in the baseline series. RESULTS: Contact
allergy to MCI/MI at 0.01% and 0.02% was found in 3.7% and 5.6% of the patients,
respectively (P < 0.001). CONCLUSIONS: Methylchloroisothiazolinone/MI 0.02% aq.
(dose, 6 MUg/cm) diagnoses significantly more contact allergy than 0.01% (dose, 3
MUg/cm), without resulting in more adverse reactions.
Methylchloroisothiazolinone/MI at 0.02% aq. should therefore be continuously used
in the international baseline series.
PMID- 28509717
TI - Unreported Sources of Nickel Exposure in Community-Based Facilities Frequented by
Children.
PMID- 28509718
TI - Contact Allergens in Food Handlers of Kashmir Valley in North India.
PMID- 28509719
TI - The Importance of Factors Related to Nurse Retention: Using the Baptist Health
Nurse Retention Questionnaire, Part 2.
AB - OBJECTIVE: The purpose of this study was to examine the importance of factors
related to nurse retention. BACKGROUND: Retaining nurses within the healthcare
system is a challenge for hospital administrators. Understanding factors
important to nurse retention is essential. METHODS: Responses of nurses (n = 279)
to the Baptist Health Nurse Retention Questionnaire (BHNRQ) at a 391-bed
Magnet(r) redesignated community hospital were analyzed to explore differences in
importance scores of bedside nurses. RESULTS: The results demonstrate that each
of the 12 items on the BHNRQ was moderately to highly important. A multivariate
analysis of variance based on generation, degree, unit, and experience revealed
no significant differences on subscale scores (nursing practice, management, and
staffing). Themes derived from the comment section on the BHNRQ were consistent
with quantitative findings. CONCLUSION: Clinical and managerial competence,
engagement with their employees, and presence on the unit are keys to retaining a
satisfied nursing workforce.
PMID- 28509720
TI - Effects of RN Age and Experience on Transformational Leadership Practices.
AB - OBJECTIVE: This study reported the evolution of transformational leadership (TL)
practices and behaviors across years of age, management experience, and
professional nursing practice within a professional nursing leadership
organization. BACKGROUND: Recent studies of CNO TL found valuations peak near age
60 years. This study reported on a wider range of management positions,
correlating years of RN practice and management experience and age to TL metrics.
METHOD: This study used Kouzes and Posner's Leadership Practices Inventory-Self
Assessment (LPI-S) to survey a nursing leadership organization, the Association
of California Nurse Leaders (ACNL). Anonymous responses were analyzed to identify
leadership trends in age and years of professional service. RESULTS: On average,
LPI-S metrics of leadership skills advance through years of management, RN
experience, and age. The TL scores are statistically higher in most LPI-S
categories for those with more than 30 years of RN or management experience.
Decade-averaged LPI-S TL metrics in the ACNL survey evolve linearly throughout
age before peaking in the decade from age 60 to 69 years. A similar evolution of
TL metrics is seen in decades of either years of management experience or years
of RN experience. Transformational leadership increased with nursing maturity
particularly for LPI-S categories of "inspire a shared vision," "challenge the
process," and "enable others to act." CONCLUSION: In the ACNL population studied,
decade-averaged leadership metrics advanced. Leadership evolution with age in the
broader RN population peaked in age bracket 60 to 69 years. The LPI-S averages
declined when older than 70 years, coinciding with a shift from full-time work
toward retirement and part-time employment.
PMID- 28509721
TI - Bundled Payments for Care Improvement: Preparing for the Medical Diagnosis
Related Groups.
AB - BACKGROUND: The Centers for Medicare and Medicaid Services Innovation Center
introduced the Bundled Payments for Care Improvement (BPCI) initiative in 2011 as
1 strategy to encourage healthcare organizations and clinicians to improve
healthcare delivery for patients, both when they are in the hospital and after
they are discharged. Mercy Health Saint Mary's, a large urban academic medical
center, engaged in BPCI primarily with a group of medical diagnosis-related
groups (DRGs). OBJECTIVES: In this article, we describe our experience creating a
system of response for the diverse people and diagnoses that fall into the
medical DRG bundles and specifically identify organizational factors for enabling
successful implementation of bundled payments. RESULTS: Our experience suggests
that interprofessional collaboration enabled program success. CONCLUSIONS:
Although still in its early phases, observations from our program's strategies
and tactics may provide potential insights for organizations considering
engagement in the BPCI initiative.
PMID- 28509722
TI - Rationale for nebivolol/valsartan combination for hypertension: review of
preclinical and clinical data.
AB - : To treat hypertension, combining two or more antihypertensive drugs from
different classes is often necessary. beta-Blockers and renin-angiotensin
aldosterone system inhibitors, when combined, have been deemed 'less effective'
based on partially overlapping mechanisms of action and limited evidence.
Recently, the single-pill combination (SPC) of nebivolol (Neb) 5 mg - a
vasodilatory beta1-selective antagonist/beta3 agonist - and valsartan 80 mg, an
angiotensin II receptor blocker, was US Food and Drug Administration-approved for
hypertension. Pharmacological profiles of Neb and valsartan, alone and combined,
are well characterized. In addition, a large 8-week randomized trial in stages I
II hypertensive patients (N = 4161) demonstrated greater blood pressure-reducing
efficacy for Neb/valsartan SPCs than component monotherapies with comparable
tolerability. In a biomarkers substudy (N = 805), Neb/valsartan SPCs prevented
valsartan-induced increases in plasma renin, and a greater reduction in plasma
aldosterone was observed with the highest SPC dose vs. valsartan 320 mg/day. This
review summarizes preclinical and clinical evidence supporting Neb/valsartan as
an efficacious and well tolerated combination treatment for hypertension.
PMID- 28509724
TI - Associations between glycaemic deterioration and aortic stiffness and central
blood pressure: the ADDITION-PRO Study.
AB - OBJECTIVES: In the context of screening for diabetes, we examined levels of
central haemodynamics among individuals with different levels of diabetes risk
and analysed the impact of glycated haemoglobin A (HbA1c) and HbA1c changes on
central haemodynamics. METHODS: A Danish population-based stepwise screening
programme for diabetes including a diabetes risk score (DRS) questionnaire and
glucose measurements identified seven groups of individuals at increasing levels
of diabetes risk. After 7.8 years of follow-up, 2048 individuals underwent aortic
stiffness assessment by carotid-femoral pulse wave velocity (aPWV) and assessment
of central blood pressure (BP). We compared differences in central haemodynamics
at follow-up between the diabetes risk groups and analysed the impact of HbA1c at
screening and HbA1c change on central haemodynamics at follow-up adjusting for
relevant confounders. RESULTS: At screening, median age was 59.0 years, and
median HbA1c was 5.7%. At follow-up, median aPWV was 8.0 m/s, and median central
SBP was 123.5 mmHg. Among individuals with high DRS, aPWV, central SBP and DBP,
and pulse pressure were higher in individuals with impaired glucose tolerance
than normal glucose tolerance. Per 1%-point higher HbA1c at screening, aPWV was
0.23 m/s (95% confidence interval: 0.00; 0.46) higher, and central DBP was 1.35
mmHg (95% confidence interval: 0.19; 2.51) lower, whereas HbA1c change was not
associated with any of the central haemodynamics. CONCLUSION: Dysglycaemia is
associated with future aortic stiffness. However, glycaemic deterioration over
7.8 years does not affect aortic stiffness or central BP independently of other
cardiometabolic risk factors.
PMID- 28509723
TI - Determinants of retinal microvascular features and their relationships in two
European populations.
AB - OBJECTIVES: To examine factors influencing retinal vasculature in two
environmentally contrasted, cross-sectional studies of adult participants of
European descent and to estimate the extent and specificity of genetic
contributions to each retinal vasculature feature. METHODS: Retinal images from
1088 participants in the Orkney Complex Disease Study and 387 in the CROATIA
Korcula study, taken using the same nonmydriatic camera system and graded by the
same person, were evaluated. Using general linear models, we estimated the
influence of an extensive range of systemic risk factors, calculated retinal
traits heritabilities and genetic correlations. MAIN RESULTS: Systemic covariates
explained little (<4%) of the variation in vessel tortuosity, substantially more
(>10%, up to 31.7%) of the variation in vessel width and monofractal dimension.
Suggestive not well trodden associations of biological interest included that of
urate, tissue plasminogen activator and cardiac PR interval with arteriolar
narrowing, that of carotid intima-media thickness with less-tortuous arterioles
and of cardiac QT interval with more tortuous venules. The genetic underpinning
of tortuosity is largely distinct from that of the other retinal vascular
features, whereas that of fractal dimension and vessel width greatly overlaps.
The previously recognized influence of ocular axial length on vessel widths was
high and can be expected to lead to artefactual genetic associations [genetic
correlation with central retinal arteriolar equivalent: -0.53 (standard error
0.11)]. The significant genetic correlation between SBP and central retinal
arteriolar equivalent, -0.53 (standard error 0.22) (after adjusting for age, sex
and axial length of the eye), augurs more favourably for the discovery of genetic
variants relevant to vascular physiology.
PMID- 28509725
TI - Telmisartan and hydrochlorothiazide antihypertensive treatment in high sodium
intake population: a randomized double-blind trial.
AB - OBJECTIVES: To compare the blood pressure (BP)-lowering effects of telmisartan 40
mg/day and hydrochlorothiazide (HCTZ) 25 mg/day in high sodium intake patients
with mild-to-moderate hypertension in China. METHODS: In this randomized, double
blind trial, eligible patients were randomly divided into telmisartan and HCTZ
groups with three follow-ups scheduled on days 15, 30, and 60 after enrollment to
compare BP decrease, hypokalemia, and other adverse events after intervention.
RESULTS: A total of 1333 mild-to-moderate hypertensive patients with average
sodium intake of 5909 mg/day were enrolled from 14 county hospitals in China.
Baseline characteristics were well balanced. At 15, 30, and 60 days of follow-up,
average SBP/DBP reduction in telmisartan and HCTZ group was 12.5/8.0, 14.3/9.1,
12.8/7.2, 11.0/5.8, 13.6/7.1, and 11.5/5.3 mmHg, respectively. Telmisartan showed
greater BP response than HCTZ at three visits, with statistical significance for
DBP (P < 0.001) regardless of the adjustment for baseline BP, sodium excretion,
and pulse pressure (PP). SBP reduction was positively related to increasing
urinary sodium and PP levels for patients in both groups but increased faster
with increasing PP in HCTZ than in telmisartan (P = 0.0238 for group * PP).
Compared with telmisartan, HCTZ showed more hypokalemia (0.4 vs. 4.5%, P <
0.001). CONCLUSION: Both telmisartan and HCTZ were effective for the treatment of
hypertensive patients with high sodium intake. Telmisartan showed better DBP
lowering effect and less hypokalemia than HCTZ among high sodium intake patients.
Further studies are needed to evaluate the plausible superiority effect of
hydrochlorothiazide among patients with large PP.
PMID- 28509726
TI - Sodium butyrate suppresses angiotensin II-induced hypertension by inhibition of
renal (pro)renin receptor and intrarenal renin-angiotensin system.
AB - OBJECTIVES: Butyrate, a short-chain fatty acid, is the end product of the
fermentation of complex carbohydrates by the gut microbiota. Recently, sodium
butyrate (NaBu) has been found to play a protective role in a number of chronic
diseases. However, it is still unclear whether NaBu has a therapeutic potential
in hypertension. The present study was aimed to investigate the role of NaBu in
angiotensin II (Ang II)-induced hypertension and to further explore the
underlying mechanism. METHODS: Ang II was infused into uninephrectomized Sprague
Dawley rats with or without intramedullary infusion of NaBu for 14 days. Mean
arterial blood pressure was recorded by the telemetry system. Renal tissues,
serum samples, and 24-h urine samples were collected to examine renal injury and
the regulation of the (pro)renin receptor (PRR) and renin. RESULTS:
Intramedullary infusion of NaBu in Sprague-Dawley rats lowered the Ang II-induced
mean arterial pressure from 129 +/- 6 mmHg to 108 +/- 4 mmHg (P < 0.01). This
corresponded with an improvement in Ang II-induced renal injury, including
urinary albumin, glomerulosclerosis, and renal fibrosis, as well as the
expression of inflammatory mediators tumor necrosis factor alpha, interleukin 6.
The renal expression of PRR, angiotensinogen, angiotensin I-converting enzyme and
the urinary excretion of soluble PRR, renin, and angiotensinogen were all
increased by Ang II infusion but decreased by NaBu treatment. In cultured
innermedullary collecting duct cells, NaBu treatment attenuated Ang II-induced
expression of PRR and renin. CONCLUSION: These results demonstrate that NaBu
exerts an antihypertensive action, likely by suppressing the PRR-mediated
intrarenal renin-angiotensin system.
PMID- 28509727
TI - Lower dementia risk with different classes of antihypertensive medication in
older patients.
AB - OBJECTIVE: Use of antihypertensive medication (AHM) is potentially associated
with a reduced risk of dementia. Both calcium channel blockers (CCBs) and
angiotensin receptor blockers (ARBs) are suggested to have a more pronounced
protective effect. We aimed to study the association between different classes of
AHM and dementia in older people. METHODS: A subgroup of community-dwelling older
people using AHM included in the 'Prevention of Dementia by Intensive Vascular
Care' randomized controlled trial was studied. Incident dementia rates in
participants with different AHM classes (mono and combination therapy) were
compared with dementia rates in participants with any other AHM. RESULTS: At
baseline, 1951 participants (55.3%) used AHM [mean age, 74.4 year (SD 2.5); mean
SBP, 156.4 mmHg (SD 21.5)]. In total, 986 participants (50.5%) used beta
blockers, 798 diuretics (40.9%), 623 angiotensin- converting enzyme inhibitors
(31.9%), 522 CCBs (26.8%), and 402 ARBs (20.6%). After 6.7 years (interquartile
range 6.0-7.3) of follow-up, 136 participants (7.0%) developed dementia. Both use
of CCBs [hazard ratio 0.56, 95% confidence interval (95% CI) 0.36-0.87] and ARBs
(hazard ratio 0.60, 95% CI 0.37-0.98) were independently associated with a
decreased risk of dementia. The association of CCBs with dementia was most
apparent in participants without a history of cardiovascular disease (hazard
ratio 0.38, 95% CI 0.18-0.81) and with uncontrolled hypertension (hazard ratio
0.26, 95% CI 0.11-0.61). SBP was not significantly lower in participants using
CCBs or ARBs. CONCLUSION: Both use of CCBs and ARBs are independently associated
with a decreased risk of dementia in older people.
PMID- 28509728
TI - Society of Critical Care Medicine Presidential Address-46th Annual Congress,
January 2017, Honolulu, Hawaii.
PMID- 28509731
TI - Greater Treatment Effect With Lower Disease Severity: VASST Insights.
PMID- 28509732
TI - Stick to What You Know: Do Visiting Intensivists Worsen Outcomes?
PMID- 28509729
TI - Generalizable Biomarkers in Critical Care: Toward Precision Medicine.
PMID- 28509733
TI - Safe at First, But Not Reaching Second: Implications of Delayed Second Doses of
Antimicrobials in Patients Presenting to Emergency Departments With Sepsis.
PMID- 28509730
TI - American College of Critical Care Medicine Clinical Practice Parameters for
Hemodynamic Support of Pediatric and Neonatal Septic Shock.
AB - OBJECTIVES: The American College of Critical Care Medicine provided 2002 and 2007
guidelines for hemodynamic support of newborn and pediatric septic shock. Provide
the 2014 update of the 2007 American College of Critical Care Medicine "Clinical
Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock."
DESIGN: Society of Critical Care Medicine members were identified from general
solicitation at Society of Critical Care Medicine Educational and Scientific
Symposia (2006-2014). The PubMed/Medline/Embase literature (2006-14) was searched
by the Society of Critical Care Medicine librarian using the keywords: sepsis,
septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric
oxide, extracorporeal membrane oxygenation, and American College of Critical Care
Medicine guidelines in the newborn and pediatric age groups. MEASUREMENTS AND
MAIN RESULTS: The 2002 and 2007 guidelines were widely disseminated, translated
into Spanish and Portuguese, and incorporated into Society of Critical Care
Medicine and American Heart Association/Pediatric Advanced Life Support
sanctioned recommendations. The review of new literature highlights two tertiary
pediatric centers that implemented quality improvement initiatives to improve
early septic shock recognition and first-hour compliance to these guidelines.
Improved compliance reduced hospital mortality from 4% to 2%. Analysis of Global
Sepsis Initiative data in resource rich developed and developing nations further
showed improved hospital mortality with compliance to first-hour and
stabilization guideline recommendations. CONCLUSIONS: The major new
recommendation in the 2014 update is consideration of institution-specific use of
1) a "recognition bundle" containing a trigger tool for rapid identification of
patients with septic shock, 2) a "resuscitation and stabilization bundle" to help
adherence to best practice principles, and 3) a "performance bundle" to identify
and overcome perceived barriers to the pursuit of best practice principles.
PMID- 28509734
TI - Inflammatory Signatures in ICU-Acquired Weakness.
PMID- 28509735
TI - The Road to Unintended Consequences Is Paved With Good Intentions.
PMID- 28509736
TI - Progressive Mobility Program in a Neuro-ICU: What Makes It Different?
PMID- 28509737
TI - Noninvasive Ventilation in the PICU: One Step Closer.
PMID- 28509738
TI - It's Been a Hard Day's Night-What Determines Impact of Less Than 24/7 Rapid
Response Systems?
PMID- 28509739
TI - Fecal Micobiota Transplantation to Treat Sepsis of Unclear Etiology.
PMID- 28509740
TI - Should We Prescribe Selective Serotonergic Reuptake Inhibitors/Serotonergic and
Noradrenergic Reuptake Inhibitors in the ICU?
PMID- 28509741
TI - To What Extent Does ABCDEF Bundle Improve Hospital Survival and Reduce Brain
Dysfunction of 1,438 Patients With Mechanical Ventilation in Seven California
Community Hospitals?
PMID- 28509742
TI - The authors reply.
PMID- 28509743
TI - The Role of Source Control in Septic Patients.
PMID- 28509744
TI - Critical Care Echocardiography Guidelines: Strength in International Cooperation
Regarding Terminology and Competency Standards.
PMID- 28509745
TI - The authors reply.
PMID- 28509746
TI - Guidelines for Family-Centered Care in Neuro-ICU Populations: Caveats for Routine
Palliative Care.
PMID- 28509747
TI - The authors reply.
PMID- 28509748
TI - Iatrogenic Withdrawal Syndrome or Undiagnosed Delirium?
PMID- 28509749
TI - The authors reply.
PMID- 28509750
TI - Renin-Angiotensin-Aldosterone System Blockade Use in Sepsis Patients: Did It
Impact Renal Outcomes?
PMID- 28509751
TI - Optimal Cutoff Value for Lung Injury Prediction Score and Potential Confounders
for Identifying the Risk of Developing Acute Respiratory Distress Syndrome.
PMID- 28509753
TI - Physician-Assisted Suicide and Euthanasia Is Incompatible With Medicine: A
Response From Medical Students.
PMID- 28509752
TI - The authors reply.
PMID- 28509754
TI - The authors reply.
PMID- 28509755
TI - Ending Life in the ICU: The Vacuity of Sanctity.
PMID- 28509756
TI - The authors reply.
PMID- 28509757
TI - More Than a Prompt May be Needed to Improve Palliative Care Discussions for
Hospitalized Patients.
PMID- 28509758
TI - Post Hoc Analysis of Automated Early Warning System Alert Linked to End-of-Life
Discussions-Is There a Racial Disparity in Effectiveness?
PMID- 28509759
TI - The author replies.
PMID- 28509760
TI - Global longitudinal strain predicts outcome after MitraClip implantation for
secondary mitral regurgitation.
AB - AIM: The aim of this study was to assess preoperative determinants, prevalence,
and prognostic impact of left ventricular (LV) reverse remodeling (LVRR) in
patients with secondary mitral regurgitation (SMR), undergoing MitraClip
implantation (MCi). METHODS: From March 2012 to January 2015, a total of 41
consecutive patients with moderate-to-severe SMR treated successfully with MCi
were enrolled. All patients underwent clinical and echocardiographic follow-up
after MCi. Global longitudinal strain (GLS) was obtained using two dimensional
speckle tracking analysis. A reduction in LV end-systolic volume more than 10%
compared with baseline was considered as a marker of LVRR. Patients were divided
into two groups according to the presence or absence of LVRR. Cardiac events were
defined as the occurrence of cardiac death, rehospitalization for worsening heart
failure, and mitral valve surgery. RESULTS: On univariable analysis, EuroSCORE II
and GLS were associated with LVRR. On multivariable logistic regression analysis,
GLS was the only independent correlate of LVRR (P = 0.004). A receiver operating
characteristic curve identified a cutoff value for GLS of -9.25% (P < 0.001)
associated with LVRR, with a sensitivity and specificity of 81 and 74%,
respectively. New York Heart Failure Association class more than 2 after MCi,
absence of LVRR after MCi, and preoperative GLS more than -9.25% were
significantly correlated with adverse cardiac events at long-term follow-up. On
multivariable logistic regression analysis, GLS was the only independent
predictor of composite adverse cardiac events at 2-year follow-up. CONCLUSION: A
worse preoperative GLS predicts no LVRR and is associated with adverse long-term
outcome after successful MCi for SMR.
PMID- 28509761
TI - Dabigatran in nonvalvular atrial fibrillation: from clinical trials to real-life
experience.
AB - : Atrial fibrillation is the most common arrhythmia in over-midlife patients. In
addition to systolic heart failure, cerebral thromboembolism represents the most
dramatic complication of this rhythm disorder, contributing to morbidity and
mortality. Traditionally, anticoagulation has been considered the main strategy
in preventing stroke and systemic embolism in atrial fibrillation patients and
vitamin K-dependent antagonists have been widely used in clinical practice.
Recently, the development of direct oral anticoagulants has certainly improved
the management of this disease, providing, for the first time, the opportunity to
go beyond vitamin K-dependent antagonists limits. In the RE-LY trial, dabigatran
150 mg twice daily was superior to warfarin in the prevention of stroke or
systemic embolism and dabigatran 110 mg twice daily was noninferior. Both doses
greatly reduced hemorrhagic stroke, and dabigatran 110 mg twice daily
significantly reduced major bleeding compared with warfarin. Based on these
results, dabigatran, a direct thrombin inhibitor, was the first direct oral
anticoagulant to receive the regulatory approval for nonvalvular atrial
fibrillation patients. To date, a specific reversal agent has just been approved
as an antidote for this molecule. This review provides a summary of randomized
trials, postmarket registries and specific clinical-settings summary on
dabigatran in nonvalvular atrial fibrillation.
PMID- 28509762
TI - Beetroot Juice Increases Human Muscle Force without Changing Ca2+-Handling
Proteins.
AB - : Dietary inorganic nitrate (NO3) supplementation improves skeletal muscle (SkM)
contractile efficiency, and although rodent literature has suggested improvements
in calcium handling or redox modifications as likely explanations, the direct
mechanism of action in humans remains unknown. PURPOSE: This study aimed to
examine the effects of 7 d of beetroot juice (BRJ) supplementation on SkM
contractile characteristics and function. METHODS: Recreationally active males (n
= 8) underwent transcutaneous electrical muscle stimulation of the vastus
lateralis for the evaluation of contractile characteristics before and after 7 d
of BRJ supplementation (280 mL.d, ~26 mmol NO3). An additional group of
individuals (n = 8) followed the same supplementation protocol but underwent SkM
biopsies pre- and post-supplementation for the determination of proteins
associated with calcium handling via Western blotting, and the ratio of
reduced/oxidized glutathione (GSH:GSSG), an indicator of cellular redox state,
via high-performance liquid chromatography (HPLC). RESULTS: After
supplementation, there was no change in maximal voluntary force production (602
+/- 50 vs 596 +/- 56 N) or electrically induced tetanic contractions. By
contrast, force production was increased at 10 Hz electrical stimulation (41.1%
+/- 2.3% vs 37.6% +/- 2.4% of peak force, P < 0.05), as was peak twitch tension
(164.0 +/- 12.5 vs 136.5 +/- 7.2 N, P < 0.01) and maximal rates of force
development and relaxation (3582.8 +/- 382.3 vs 2575.7 +/- 196.2 and -2752.4 +/-
423.9 vs -2104.4 +/- 249.0 N.s, respectively, P < 0.05). Despite these
measurements implicating a change in calcium handling, the content of associated
proteins (SERCA1a, SERCA2a, dihydropyradine receptor, ryanodine receptor, and
calsequestrin) and the GSH:GSSG ratio were unaltered by BRJ. CONCLUSION: BRJ
supplementation increases force production at low-stimulation frequencies;
however, in human SkM, this is independent of changes in redox stress or the
expression of protein targets associated with calcium handling.
PMID- 28509763
TI - Achilles Tendon Load is Progressively Increased with Reductions in Walking Speed.
AB - INTRODUCTION: Achilles tendon rehabilitation protocols commonly recommend a
gradual increase in walking speed to progressively intensify tendon loading. This
study used transmission-mode ultrasound to evaluate the influence of walking
speed on loading of the human Achilles tendon in vivo. METHODS: Axial
transmission speed of ultrasound was measured in the right Achilles tendon of 33
adults (mean +/- SD: age, 29 +/- 3 yr; height, 1.725 +/- 0.069 m; weight, 71.4 +/
19.9 kg) during unshod, steady-state treadmill walking at three speeds (slow,
0.85 +/- 0.12 ms; preferred, 1.10 +/- 0.13 m.s; fast, 1.35 +/- 0.20 m.s). Ankle
kinematics, spatiotemporal gait parameters and vertical ground reaction force
were simultaneously recorded. Statistical comparisons were made using repeated
measures ANOVA models. RESULTS: Increasing walking speed was associated with
higher cadence, longer step length, shorter stance duration, greater ankle
plantarflexion, higher vertical ground reaction force peaks, and a greater
loading rate (P < 0.05). Maximum (F1,38 = 7.38, P < 0.05) and minimum (F1,46 =
8.95, P < 0.05) ultrasound transmission velocities in the Achilles tendon were
significantly lower (16-23 m.s) during the stance but not swing phase of gait,
with each increase in walking speed. CONCLUSIONS: Despite higher vertical ground
reaction forces and greater ankle plantarflexion, increasing walking speed
resulted in a reduction in the axial transmission velocity of ultrasound in the
Achilles tendon; indicating a speed-dependent reduction in tensile load within
the triceps surae muscle-tendon unit during walking. These findings question the
rationale for current progressive loading protocols involving the Achilles
tendon, in which reduced walking speeds are advocated early in the course of
treatment to lower Achilles tendon loads.
PMID- 28509764
TI - Environmental and Physiological Factors Affect Football Head Impact Biomechanics.
AB - PURPOSE: Recent anecdotal trends suggest a disproportionate number of head
injuries in collegiate football players occur during preseason football camp. In
warmer climates, this season also represents the highest risk for heat-related
illness among collegiate football players. Because concussion and heat illnesses
share many common symptoms, we need 1) to understand if environmental conditions,
body temperature, and hydration status affect head impact biomechanics; and 2) to
determine if an in-helmet thermistor could provide a valid measure of
gastrointestinal temperature. METHODS: A prospective cohort of 18 Division I
college football players (age, 21.1 +/- 1.4 yr; height, 187.7 +/- 6.6 cm; mass,
114.5 +/- 23.4 kg). Data were collected during one control and three experimental
sessions. During each session, the Head Impact Telemetry System recorded head
impact biomechanics (linear acceleration, rotational acceleration, and severity
profile) and in-helmet temperature. A wet bulb globe device recorded
environmental conditions, and CorTempTM Ingestible Core Body Temperature Sensors
recorded gastrointestinal temperature. RESULTS: Our findings suggest that linear
acceleration (P = 0.57), rotational acceleration (P = 0.16), and Head Impact
Technology severity profile (P = 0.33) are not influenced by environmental or
physiological conditions. CONCLUSIONS: We did not find any single or combination
of predictors for impact severity. Rotational acceleration was approaching
significance between our early experimental sessions when compared with our
control session. More research should be conducted to better understand if
rotational accelerations are a component of impact magnitudes that are affected
due to changes in environmental conditions, body temperature, and hydration
status.
PMID- 28509766
TI - Brown adipose tissue detected by PET/CT imaging is associated with less central
obesity.
AB - PURPOSE: This retrospective review was performed to determine whether patients
with brown adipose tissue (BAT) detected by fluorine-18-fluorodeoxyglucose (F
FDG) PET/computed tomography (CT) imaging have less central obesity than BMI
matched control patients without detectable BAT. PATIENTS AND METHODS: Thirty
seven adult oncology patients with F-FDG BAT uptake were retrospectively
identified from PET/CT studies from 2011 to 2013. The control cohort consisted of
74 adult oncology patients without detectable F-FDG BAT uptake matched for
BMI/sex/season. Tissue fat content was estimated by CT density (Hounsfield units)
with a subsequent noise removal step. Total fat and abdominal fat were
calculated. An automated separation algorithm was utilized to determine the
visceral fat and subcutaneous fat at the L4/L5 level. In addition, liver density
was obtained from CT images. CT imaging was interpreted blinded to clinical
information. RESULTS: There was no difference in total fat for the BAT cohort
(34+/-15 l) compared with the controls (34+/-16 l) (P=0.96). The BAT cohort had
lower abdominal fat to total fat ratio compared with the controls (0.28+/-0.05
vs. 0.31+/-0.08, respectively; P=0.01). The BAT cohort had a lower visceral
fat/(visceral fat+subcutaneous fat) ratio compared with the controls (0.30+/-0.10
vs. 0.34+/-0.12, respectively; P=0.03). Patients with BAT had higher liver
density, suggesting less liver fat, compared with the controls (51.3+/-7.5 vs.
47.1+/-7.0 HU, P=0.003). CONCLUSION: The findings suggest that active BAT
detected by F-FDG PET/CT is associated with less central obesity and liver fat.
The presence of foci of BAT may be protective against features of the metabolic
syndrome.
PMID- 28509770
TI - Tumescent anaesthesia: its applications and well tolerated use in the out-of
operating room setting.
AB - PURPOSE OF REVIEW: Tumescent anaesthesia is a method of administering dilute
local anaesthetic into the subcutaneous tissue. Many anaesthesiologists are
unfamiliar with the technique, its applications and potential risks. RECENT
FINDINGS: The maximum safe dose of lidocaine with epinephrine in tumescent
anaesthesia for liposuction is probably between 35 and 55 mg/kg. Without
liposuction, the maximum dose of lidocaine with epinephrine should be no more
than 28 mg/kg. After tumescent infiltration for liposuction, serum lidocaine
concentrations peak between 12 and 16 h after injection. When tumescent lidocaine
without epinephrine is used for endovenous laser therapy, peak serum lidocaine
concentrations are observed much earlier, between 1 and 2 h after injection. Slow
administration of more dilute concentrations of local anaesthetic decreases the
risk of local anaesthetic systemic toxicity. SUMMARY: Although appealing because
of its ability to provide prolonged analgesia, high doses of local anaesthetic
are frequently administered using the tumescent technique, and absorption of
local anaesthetic from the subcutaneous tissue is variable. When caring for
patients having procedures in which tumescent anaesthesia is used, the risk of
local anaesthetic toxicity should be acknowledged and lipid emulsion should be
available for prompt treatment if needed.
PMID- 28509765
TI - Multicenter, real-life experience with checkpoint inhibitors and targeted therapy
agents in advanced melanoma patients in Switzerland.
AB - Metastatic melanoma is a highly aggressive disease. Recent progress in
immunotherapy (IT) and targeted therapy (TT) has led to significant improvements
in response and survival rates in metastatic melanoma patients. The current
project aims to determine the benefit of the introduction of these new therapies
in advanced melanoma across several regions of Switzerland. This is a
retrospective multicenter analysis of 395 advanced melanoma patients treated with
standard chemotherapy, checkpoint inhibitors, and kinase inhibitors from January
2008 until December 2014. The 1-year survival was 69% (n=121) in patients treated
with checkpoint inhibitors (IT), 50% in patients treated with TTs (n=113), 85% in
the IT+TT group (n=66), and 38% in patients treated with standard chemotherapy
(n=95). The median overall survival (mOS) from first systemic treatment in the
entire study cohort was 16.9 months. mOS of patients treated either with
checkpoint or kinase inhibitors (n=300, 14.6 months) between 2008 and 2014 was
significantly improved (P<0.0001) compared with patients treated with standard
chemotherapy in 2008-2009 (n=95, 7.4 months). mOS of 61 patients with brain
metastases at stage IV was 8.1 versus 12.5 months for patients without at stage
IV (n=334), therefore being significantly different (P=0.00065). Furthermore, a
significant reduction in hospitalization duration compared with chemotherapy was
noted. Treatment with checkpoint and kinase inhibitors beyond clinical trials
significantly improves the mOS in real life and the results are consistent with
published prospective trial data.
PMID- 28509771
TI - Sedation for advanced procedures in the bronchoscopy suite: proceduralist or
anesthesiologist?
AB - PURPOSE OF REVIEW: This article focuses on the issue of sedation provided either
by proceduralists or anesthesiologists for advanced bronchoscopy procedures. The
relative merits of both approaches are presented. Current evidence from the
literature and guideline recommendations relevant to this topic are reviewed.
RECENT FINDINGS: In general, patient and proceduralist satisfaction as well as
patient safety are increased when intravenous sedation is provided for advanced
bronchoscopic procedures. However, guidelines by various societies remain vague
on defining the appropriate level of care required when providing sedation for
these procedures. In addition, targeted depth of sedation varies considerably
among practitioners. While in some settings, nonanesthesiologist-administered
propofol sedation has been proven safe; nevertheless, its use is controversial,
especially in the bronchoscopy suite. SUMMARY: The role of the anesthesiologist
in sedation for advanced bronchoscopy remains undefined. When deep sedation for
prolonged interventional procedures is needed or when dealing with patients who
have multiple comorbidities, an anesthesiologist should be involved.
PMID- 28509772
TI - Safety of deep sedation in the endoscopy suite.
AB - PURPOSE OF REVIEW: As the complexity of endoscopic procedures increases, the use
of propofol and the desire for deep sedation are becoming more common in the
endoscopy suite. This review explores sedation depth, agents used for sedation,
recommended monitoring, and adverse event risks that occur during sedation for
endoscopy. RECENT FINDINGS: The sedation provider for endoscopy varies by
practice location and with regulatory requirements. As increasingly deep levels
of sedation are used in this setting, the need for all providers to have training
in the ability to rescue patients from sedation-related side effects is
paramount. Propofol has an important role for prolonged and uncomfortable
endoscopic interventions and has a strong safety record in the endoscopy suite.
Vital signs monitoring is recommended during all endoscopy sedation, and there is
emerging interest in advanced monitoring (e.g., capnography, processed
electroencephalogram, respiratory monitoring) in this setting. The reported rate
of adverse events during endoscopy sedation varies widely; however, advanced age
and increasing American Society of Anesthesiologists physical status score are
consistently associated with increased risk. Whether anesthesiologist
administered sedation is safer than non-anesthesiologist-administered sedation
remains controversial. SUMMARY: This review provides some guidance to providers
who administer sedation in the endoscopy suite and is intended to improve the
safety of patients. The recommendations are based on best available evidence and
expert opinion.
PMID- 28509773
TI - Perioperative management of antithrombotic therapies.
AB - PURPOSE OF REVIEW: Perioperative coagulation management is becoming increasingly
frequent in the daily routine of the anesthesiologist and with the plethora of
new substances on the market also increasingly complex. The perioperative setting
poses unique challenges requiring an individualized evaluation and management of
antithrombotic therapy. This review shall summarize the newest developments in
this domain. RECENT FINDINGS: New data in patients with atrial fibrillation have
led to a paradigm change in the perioperative management of antithrombotics. The
role of bridging therapy has been downgraded in the guidelines, which only
foresee bridging in patients with high thromboembolic risk. Furthermore, direct
oral anticoagulants are now a cornerstone in antithrombotic therapy, calling for
specific perioperative management. The new reversal agents idarucizumab, and
potentially in the future andexanet alfa and ciraparantag, will play an
increasingly important role in the treatment of major bleeding in this group of
patients. SUMMARY: With the new evidence and treatment options available,
perioperative coagulation management is experiencing a Renaissance, opening many
interesting new doors, but also presenting the clinician with new challenges.
PMID- 28509774
TI - The role of the anaesthesiologist in air ambulance medicine.
AB - PURPOSE OF REVIEW: The care administered on air ambulances has become increasing
complex. This has led to a discussion among experts as to whether air ambulance
travel should be manned by physicians. This review provides evidence in support
of anaesthesiologists being the physician-leaders in air ambulance medicine,
because of their training in advanced airway management, critical care, and
resuscitation. RECENT FINDINGS: Successful prehospital care requires the ability
to perform a complex set of advanced diagnostics and interventions. These include
airway management, haemorrhage control, pain management, point-of-care
diagnostics, complex interfacility transport, and advanced interventions. This
skill set closely mirrors the training and expertise of anaesthesiologists.
SUMMARY: There are few studies investigating the specific benefit of
anaesthesiologists in air ambulance medicine. However, current evidence indicates
that their presence does improve patient care and safety. Future studies on this
topic should use evidence-based quality indicators and standardized data sets to
seek answers to optimal staffing of air ambulance teams.
PMID- 28509775
TI - Failed Vocalis Muscle Monitoring During Thyroid Surgery Resulting From Residual
Muscle Relaxation.
PMID- 28509776
TI - Hyperleukocytosis Complicated by Intracerebral Hemorrhage and Spurious Hypoxemia:
A Case Report and Literature Review.
AB - We present the management of a 15-year-old girl with acute myeloid leukemia who
presented with massive hyperleukocytosis and neurological deficit due to
intracerebral hemorrhage. Surgical intervention was considered but ultimately not
undertaken because of the presence of massive hyperleukocytosis,
thrombocytopenia, hypokalemia, and considerable discrepancy between the oxygen
saturation values determined mechanically and by peripheral oximetry. Aggressive
treatment of the hyperleukocytosis was immediately started, which improved the
patient's overall condition and rendered surgical intervention unnecessary. This
report shows that immediate treatment of massive hyperleukocytosis and critical
interpretation of laboratory results in patients with hyperleukocytosis are
warranted.
PMID- 28509777
TI - Ultrasound-Guided Percutaneous Cryoneurolysis for Acute Pain Management: A Case
Report.
AB - We report 3 different cases in which ultrasound-guided percutaneous
cryoneurolysis was performed to treat acute pain: 1 patient with refractory
incisional pain after percutaneous nephrolithotomy; 1 patient with burns to the
foot; and 1 patient with pain from iliac crest grafting. Acute pain associated
with surgery or injury is a challenge to treat with local anesthetic-based
regional anesthesia techniques when the anticipated pain duration exceeds a few
days. Cryoneurolysis is an alternative analgesic method that utilizes extremely
cold temperatures to reversibly ablate peripheral nerves and is potentially a
novel method for acute pain management.
PMID- 28509778
TI - Multiple Anesthetic Drug Sensitization in a Hairdresser With Previous Immediate
Type Hypersensitivity to Penicillin: A Case Report.
AB - Risk factors for intraoperative immediate-type hypersensitivity reactions may
require allergological evaluation. We report the case of a hairdresser with a
positive history of penicillin hypersensitivity and anaphylactic shock during
previous general anesthesia, whose in vivo and in vitro allergy tests were
positive for neuromuscular blocking agents, opioids, and midazolam. Immediate
type hypersensitivity reactions to antibiotics and professional exposure to
hairdressing products might induce simultaneous cross-sensitization to multiple
drugs that are commonly used during general anesthesia.
PMID- 28509779
TI - Gas Embolism During Hysteroscopic Surgery?: Three Cases and a Literature Review.
AB - During a period of 1 month, 3 episodes of probable or actual venous air embolism
occurred during hysteroscopic surgery. All patients developed the same symptoms
of ventilatory and hemodynamic decompensation, beginning with a reduction in end
tidal carbon dioxide, arterial desaturation, and cyanosis on the upper trunk, and
rapidly progressed to hypotension and 2 cardiac arrests. While entrainment of
some air is common during hysteroscopy, life-threatening embolism is a rare but
serious complication for which an anesthetist needs to be vigilant and prepared.
If even a small drop in end-tidal carbon dioxide occurs, venous air embolism
should be suspected and the operation should be discontinued.
PMID- 28509780
TI - Hypnosis and Axillary Compartment Block for Breast Cancer Surgery: A Case Report.
AB - Hypnosis has been proven to be a powerful tool in the management of anxiety and
pain. It allows for an increase of pain threshold, which can reach the level of
surgical analgesia. Recently injection of local anesthetics around the serratus
muscle has been presented as an alternative to paravertebral block for cancer
breast surgery. We report the successful use of hypnosis in combination with an
axillary compartment block for lumpectomy and axillary lymph node dissection.
PMID- 28509781
TI - Correction of Severe Coagulopathy and Hyperfibrinolysis by Tranexamic Acid and
Recombinant Factor VIIa in a Cirrhotic Patient After Trauma: A Case Report.
AB - Coagulopathy induced by trauma or cirrhosis is a well-recognized entity.
Viscoelastic testing has been used in either condition for goal-directed
transfusion and detection of fibrinolysis since conventional coagulation tests do
not correlate with clinical risk of bleeding. Hemostatic resuscitation may not be
adequate for a trauma patient with liver disease due to complex alterations in
coagulation systems and occasionally require adjuvant therapy. We report a case
of trauma-induced coagulopathy presenting as severe hyperfibrinolysis in a
cirrhotic patient who was refractory to hemostatic resuscitation but was rapidly
corrected by the administration of tranexamic acid and recombinant Factor VIIa.
PMID- 28509782
TI - An update on the impact of food allergy on anxiety and quality of life.
AB - PURPOSE OF REVIEW: Food allergies have become more common, and management
involves dietary avoidance that can impair quality of life. Patients and families
must manage the daily risk of anaphylaxis at each meal. The purpose of this
review is to describe the impact of food allergies on quality of life and to
provide an update on new developments in food allergy management, particularly
peanut allergy. RECENT FINDINGS: Food allergy requires careful avoidance of
common and ubiquitous dietary allergens. Living with food allergy is associated
with annual economic costs in excess of $4000 per child, in addition to risks of
anxiety and depressive symptoms. An expert panel sponsored by the 2017 National
Institute of Allergy and Infectious Diseases published addendum guidelines for
the prevention of peanut allergy, which suggest three separate approaches to
peanut protein introduction for infants at various levels of risk. SUMMARY:
Clinicians must be aware of underappreciated burdens faced by children and
families with food allergies. Management involves a partnership between primary
and specialty care. Mitigation strategies to improve quality of life for patients
include efforts to avoid overdiagnosis in synergy with balanced counseling about
the risks of food allergies. Experimental food allergen desensitization can
improve quality of life but remains investigational at this time. For patients
with significant anxiety, interdisciplinary management involving professional
counseling may be helpful. Risk stratification and early introduction of peanut
protein can help prevent the development of peanut allergy.
PMID- 28509783
TI - The evaluation of adolescent chest pain: a screening ECG or PSC-17?
AB - PURPOSE OF REVIEW: The present review offers an update on entities presenting as
chest pain in the adolescent population. It discusses recently proposed tools and
shared mental models used in primary and urgent care settings to evaluate chest
pain, and their focus on identifying life-threatening processes. We consider
whether the current practice may be improved by accounting for the increasingly
recognized non-life-threatening causes of adolescent chest pain. RECENT FINDINGS:
The present experiences and behaviors of adolescents have added new causes of
chest pain to the work-up of this disquieting chief complaint. The initial
approach to adolescent chest pain has classically focused on ruling out life
threatening entities, and current diagnostic algorithms offer systematic
approaches with similar emphases. A growing body of literature on the nonlife
threatening causes of adolescent chest pain, often categorized as idiopathic,
suggests a need to reevaluate our practice. SUMMARY: Adolescent chest pain is
most often noncardiac and non-life threatening in nature, yet current diagnostic
algorithms and evaluations emphasize identifying the exceptional case of cardiac
chest pain. Familiarizing ourselves with the more common causes of chest pain and
with our present approach to the evaluation of this particular chief complaint,
may help us to better counsel our patients and avoid unnecessary use of valuable
resources.
PMID- 28509784
TI - Pharmacotherapy options for pediatric diabetes.
AB - PURPOSE OF REVIEW: Type 1 diabetes (T1D) and type 2 diabetes (T2D) are frequent
conditions during childhood and adolescence. The present review offers an update
on current available treatment strategies for T1D and T2D approved for use in
children and adolescents. RECENT FINDINGS: Insulin remains the main and essential
therapeutic strategy in youth with T1D. A second generation of insulin analogues
is being evaluated and could help in improving glycemic control. Over the last
decades advances in technology have allowed the implementation of insulin pump
therapy and continuous glucose monitoring, and are now leading the way towards
the development of an artificial pancreas or closed loop system.Treatment of T2D
is based on lifestyle interventions and metformin as the first-line drug to be
used. Little evidence is available for other oral hypoglycemic drugs, currently
used in adults. SUMMARY: Although much progress has been made in the field of
diabetes management, there are still several unmet goals. One of the main issues
is to develop a system allowing more physiological insulin coverage. For both T1D
and T2D, there is a strong need of new drugs to be used alone or in combination,
mainly in patients struggling to achieve good glycemic control.
PMID- 28509785
TI - Inflammatory bowel disease treatment in Eastern Europe: current status,
challenges and needs.
AB - PURPOSE OF REVIEW: To analyze the available studies of course, diagnosis and
treatment of Inflammatory bowel disease (IBD) in Eastern Europe. RECENT FINDINGS:
According to published data, full epidemiological studies were conducted only in
Czech Republic, Estonia, Hungary and Romania. Russia was recently included in the
EpiCom study, although only Moscow region data were provided. SUMMARY: We
summarize previously published and unpublished data on the epidemiology, IBD
diagnosis and treatment in Eastern Europe. In addition, changes during several
years are presented. These data show that IBD epidemiology in Eastern Europe
corresponds to the previously known patterns, and that the quality of IBD health
care has improved in the last several years.
PMID- 28509786
TI - IgG4-related disease of the biliary tract and pancreas: clinical and experimental
advances.
AB - PURPOSE OF REVIEW: IgG4-related disease (IgG4-RD) is an immune-mediated disease
of unknown cause. It predominantly affects the biliary tract [IgG4-associated
cholangitis (IAC)] and pancreas [autoimmune pancreatitis (AIP)] of mostly elderly
men. Accurate diagnostic tests are lacking. Patients benefit from predniso(lo)ne
treatment. However, disease relapse is often seen. This review will address
pathophysiological aspects and advances in diagnostic and therapeutic strategies.
RECENT FINDINGS: The role of IgG1 and IgG4 in the pathophysiology of IgG4-RD was
studied in mice which showed more intense organ damage of pancreas and salivary
glands when IgG1 rather than IgG4 of patients with IgG4-RD was injected.
Coadministration of IgG1+IgG4 led to dampening of IgG1-mediated injury supporting
the view that IgG4 exerts immune-dampening effects. IgG4+ B-cell receptor clones
identified by next-generation sequencing and the IgG4/IgG RNA ratio in human
blood assessed by quantitative PCR were able to accurately distinguish IAC/AIP
from primary sclerosing cholangitis or pancreatobiliary malignancies. Long-term
treatment with low-dose prednisolone was safe and reduced the number of flare-ups
in patients with AIP. SUMMARY: Early diagnosis by a novel accurate and easy-to
use qPCR test may prevent life-threatening complications, unnecessary
interventions and fatal course because of misdiagnosis. Prednisolone treatment
remains the standard of care in patients with IgG4-RD.
PMID- 28509793
TI - Remifentanil Dosing at Extremes of Body Weight.
PMID- 28509794
TI - An Allometric Model of Remifentanil Pharmacokinetics and Pharmacodynamics.
AB - BACKGROUND: Pharmacokinetic and pharmacodynamic models are used to predict and
explore drug infusion schemes and their resulting concentration profiles for
clinical application. Our aim was to develop a pharmacokinetic-pharmacodynamic
model for remifentanil that is accurate in patients with a wide range of age and
weight. METHODS: Remifentanil pharmacokinetic data were obtained from three
previously published studies of adults and children, one of which also contained
pharmacodynamic data from adults. NONMEM was used to estimate allometrically
scaled compartmental pharmacokinetic and pharmacodynamic models. Weight, age,
height, sex, and body mass index were explored as covariates. Predictive
performance was measured across young children, children, young adults, middle
aged, and elderly. RESULTS: Overall, 2,634 remifentanil arterial concentration
and 3,989 spectral-edge frequency observations from 131 individuals (55 male, 76
female) were analyzed. Age range was 5 days to 85 yr, weight range was 2.5 to 106
kg, and height range was 49 to 193 cm. The final pharmacokinetic model uses age,
weight, and sex as covariates. Parameter estimates for a 35-yr-old, 70-kg male
(reference individual) are: V1, 5.81 l; V2, 8.82 l; V3, 5.03 l; CL, 2.58 l/min;
Q2, 1.72 l/min; and Q3, 0.124 l/min. Parameters mostly increased with fat-free
mass and decreased with age. The pharmacodynamic model effect compartment rate
constant (ke0) was 1.09 per minute (reference individual), which decreased with
age. CONCLUSIONS: We developed a pharmacokinetic-pharmacodynamic model to predict
remifentanil concentration and effect for a wide range of patient ages and
weights. Performance exceeded the Minto model over a wide age and weight range.
PMID- 28509796
TI - Disposition of Remifentanil in Obesity: A New Pharmacokinetic Model Incorporating
the Influence of Body Mass.
AB - BACKGROUND: The influence of obesity on the pharmacokinetic (PK) behavior of
remifentanil is incompletely understood. The aim of the current investigation was
to develop a new population PK model for remifentanil that would adequately
characterize the influence of body weight (among other covariates, e.g., age) on
the disposition of remifentanil in the general adult population. We hypothesized
that age and various indices of body mass would be important covariates in the
new model. METHODS: Nine previously published data sets containing 4,455 blood
concentration measurements from 229 subjects were merged. A new PK model was
built using nonlinear mixed-effects modeling. Satisfactory model performance was
assessed graphically and numerically; an internal, boot-strapping validation
procedure was performed to determine the CIs of the model. RESULTS: Body weight,
fat-free body mass, and age (but not body mass index) exhibited significant
covariate effects on certain three-compartment model parameters. Visual and
numerical assessments of model performance were satisfactory. The bootstrap
procedure showed satisfactory CIs on all of the model parameters. CONCLUSIONS: A
new model estimated from a large, diverse data set provides the PK foundation for
remifentanil dosing calculations in adult obese and elderly patients. It is
suitable for use in target-controlled infusion systems and pharmacologic
simulation.
PMID- 28509801
TI - Images in Anesthesiology: Anomalous Single Coronary Artery from the Pulmonary
Artery.
PMID- 28509802
TI - Measurement of Patient Outcomes Important.
PMID- 28509803
TI - In Reply.
PMID- 28509804
TI - Video Laryngoscopes and Best Rescue Strategy for Unexpected Difficult Airways: Do
Not Forget a Combined Approach with Flexible Bronchoscopy!
PMID- 28509805
TI - In Reply.
PMID- 28509806
TI - Advances in management of hepatocellular carcinoma.
AB - PURPOSE OF REVIEW: Hepatocellular carcinoma (HCC) is one of the leading causes of
death by cancer worldwide due to a dismal prognosis. The aim of this review is to
summarize the main advances in the pathophysiology and management of HCC. RECENT
FINDINGS: Genomic analysis has recently delineated the key signaling pathways
aberrantly deregulated in HCC (telomere maintenance, cell cycle gene, Wnt/beta
catenin, epigenetic modifier, oxidative stress etc.). Major advances in the
clinical care of patients with HCC are helping to refine the diagnosis algorithm
and tumor staging. Extension of criteria for liver transplantation, but also for
liver resection and percutaneous ablation, aims to increase the number of
patients being treated in a curative attempt. Moreover, radioembolization is a
competitor for transarterial chemoembolization in Barcelona clinic liver cancer B
patients, and sorafenib in Barcelona clinic liver cancer C with tumor portal
thrombosis. In advanced HCC, sorafenib is the standard of first-line care and
regorafenib as a second line. SUMMARY: New concepts on liver resection,
percutaneous ablation or liver transplantation aim to extend the numbers of
patients treated for HCC in curative attempts. Moreover, immunotherapy (anti
death protein 1) and biotherapy adapted to tumor biology seem promising and are
currently being tested in advanced stages.
PMID- 28509807
TI - Treatment of retroperitoneal sarcoma: current standards and new developments.
AB - PURPOSE OF REVIEW: Retroperitoneal sarcomas are rare tumors and with complex
treatment. In this manuscript we give an overview of current standards in
treatment of this disease and discuss new developments. RECENT FINDINGS: Surgery
with complete resection of the primary tumor is still the only curative modality.
The role of preoperative radiotherapy is not clear and is currently being
investigated in a clinical trial. Neo-adjuvant chemotherapy is not the standard
of care but can be considered occasionally when complete resection is uncertain.
Local and distant recurrent disease carries a dismal prognosis, although long
term survival can be achieved. Liposarcomas tend to recur locally, whereas
distant recurrences are more often seen in leiomyosarcoma and other subtypes.
Outcome improves when patients are treated in high volume sarcoma centers. In the
metastatic setting, newer systemic agents have recently been approved. SUMMARY:
Treatment of retroperitoneal sarcomas is complex and all patients should be
treated in multidisciplinary sarcoma centers. Increasing international
collaboration of expert centers in sharing expertise and performing clinical
trials might lead to better treatment and improved survival.
PMID- 28509808
TI - Implementing patient information for gynae-oncology patients at a tertiary
referral health service.
AB - AIM: To ensure that gynae-oncology surgical patients receive relevant written
information, in their preferred format, and at a time that suits them, according
to the best available evidence. METHODS: This project utilized an audit and
feedback design and was conducted over a 9-month period from August 2015 to May
2016. Twenty-nine patients were audited prior to two strategies being
implemented. The first strategy was a standardized e-mail letter to all patients
(containing links to surgical information, cancer support websites and a short
video introducing hospital staff, and the second was a discharge information
sheet detailing wound care, signs of complications, actions to take and follow-up
instructions. Thirty patients were audited post-implementation to evaluate the
success of these strategies. RESULTS: There were significant increases in the
number of patients who said they received written information on their diagnosis,
surgery and potential complications at initial consultation and a significant
increase in the number of patients who said they were provided with written
follow-up information on discharge. Pre-audit, 83% of patients stated they would
like to receive a list of reliable websites to access and post-audit, 89% of
patients stated they found the websites provided were useful. DISCUSSION:
Although gynae-oncology surgical patients did previously receive relevant verbal
information, little or no written information was provided. The pre
implementation audit provided insight into the information these patients
required. The e-mail was generally well received by patients; however; there was
a minority who did not have internet access and therefore a paper version was
provided. CONCLUSION: This project identified deficits in the provision of
written information for surgical gynae-oncology patients. Two strategies were
implemented to address this deficit with positive results in the number of
patients receiving written information; however, further investigation is needed
to establish patient satisfaction with this information.
PMID- 28509810
TI - The triple C (consultation, collaboration and consolidation) model: a way forward
to sustainability of evidence into practice.
PMID- 28509809
TI - Evidence-based practice among health professionals in hospitals of Northwest
Ethiopia: a cross-sectional study.
AB - BACKGROUND: Evidence-based practice (EBP) is a problem-solving approach to
patient care based on the best available and valid evidence. It is accentuated to
increase the quality of care and patient safety. EBP in clinical service is low
in developing countries including Ethiopia. This study aimed at assessing EBP and
associated factors among health professionals in North Gondar Administrative Zone
hospitals, Northwest Ethiopia. METHODS: Institution-based cross-sectional study
was carried out from March to May 2015 in three hospitals in North Gondar Zone. A
stratified simple random sampling technique was used to select 438 respondents.
Trained data collectors collected data using a pre-tested, structured and self
administered questionnaire. The questionnaire included sociodemographic
characteristics, level of knowledge, attitude and organizational factors. Data
were entered using Epi Info version 7.0 and analysed using SPSS version 20.0.
Bivariate and multivariable logistic regression analyses were undertaken to
identify the associated factors. RESULTS: In total, 431 returned questionnaires
were valid for the analysis making a response rate of 98.4%. Almost half, 53%
(228) of study participants utilized EBP. EBP utilization was significantly
associated with knowledge [adjusted odds ratio (AOR): 1.612, 95% confidence
interval (CI) = (1.06-2.45)], Internet access [AOR: 1.831, 95% CI = (1.191
2.816)], training [AOR: 1.906, 95% CI (1.223-2.97)], and availability of enough
time to apply EBP [AOR: 1.698, 95% CI = (1.122-2.57)]. CONCLUSION: This study
depicts EBP utilization was insufficient. We observed that knowledge of EBP,
training, Internet access and availability of time were significantly associated
with utilizing EBP. Improving facilities Internet access, giving more time for
EBP, and training health professionals about search strategies would improve EBP.
PMID- 28509811
TI - Implementation of a new method to track propofol in an endoscopy unit.
AB - AIM: Propofol is a widely used anesthesia induction agent and is easily
accessible in most healthcare facilities. Unlike regulated or schedule drugs,
propofol is inconsistently tracked, leading to inaccurate inventories, incorrect
billing, and unrecognized diversion. The goal of this project was to implement a
new method of tracking propofol in a single setting, with the aim of accounting
for 100% of the drug. METHODS: For two, 2-week observation periods, data were
extracted from an automated medication management system or pharmacy inventory
system, anesthesia records, and pharmacy billing sheets for cases in a
Gastrointestinal (GI) Endoscopy Unit, and compared pre-implementation and post
implementation of a new tracking and accounting protocol. Variables included
amount of propofol inventoried, dispensed, administered, returned, billed,
wasted, and missing. RESULTS: Pre-implementation (n = 300), 10% cases had no
record of propofol removal from the automated medication system. Of the 90% that
did, 25% had an amount signed out that did not match the amount administered.
Thirty-one percent of all propofol was unaccounted for during this 2-week period.
Furthermore, 19.7% of cases did not have a billing form located. Post
implementation of the process change, unaccounted for propofol decreased to 26%
of all cases (P = ns). The percentage of missing billing forms decreased from
19.7 to 5.8% (P = 0.00). CONCLUSION: Data suggest notable amounts of propofol
were unaccounted for and not billed for in the GI Endoscopy Unit prior to the
protocol change. Post-protocol change data reveal modest improved accounting of
the medication and significant cost-capture. Improvements may enhance inventory
reconciliation, availability of drug stock, and potentially result in a decreased
risk of unrecognized diversion.
PMID- 28509812
TI - Ospemifene's effects on lipids and coagulation factors: a post hoc analysis of
phase 2 and 3 clinical trial data.
AB - OBJECTIVE: To evaluate the effect of ospemifene 60 mg on the lipid and
coagulation parameters of postmenopausal women using data from five phase 2 and 3
clinical trials. METHODS: Data for lipids and coagulation factors for 2,166
postmenopausal women were pooled from five randomized, placebo-controlled
studies. Lipid and coagulation parameters included in this analysis were total
cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL),
triglycerides, activated partial thromboplastin time (aPTT), fibrinogen,
antithrombin antigen, protein C Ag, and protein S Ag free. RESULTS: Mean percent
changes in HDL and LDL were significantly greater with ospemifene versus placebo
at month 3 (HDL: 4.4% vs 0.2%; LDL: -5.2% vs 2.4%), month 6 (HDL: 5.1% vs 1.5%;
LDL: -6.7% vs 2.4%), and month 12 (HDL: 2.3% vs -1.9%; LDL: -7.0% vs -2.1%; P <
0.05, for all comparisons). Ospemifene significantly reduced total cholesterol at
6 months (-1.8% vs 1.6%; P = 0.0345 versus placebo), and changes in triglycerides
with ospemifene were similar to placebo at all three time points. In subgroup
analyses based on age, body mass index, and baseline triglyceride level,
ospemifene increased HDL and decreased LDL, but had no significant effect on
total cholesterol and triglycerides relative to placebo. Ospemifene significantly
improved fibrinogen and protein C antigen levels relative to placebo at months 3
(-8.7% vs -0.8% and -2.7% vs 0.5%, respectively), 6 (-6.0% vs 6.7% and -3.6 vs
8.0%), and 12 (-8.7% vs 7.3% and -4.5% vs 6.6%; P < 0.01, for all). The levels of
all coagulation factors remained within the normal range throughout the studies.
CONCLUSION: Ospemifene 60 mg does not have a detrimental effect on lipid and
coagulation parameters of postmenopausal women with up to 12 months of use.
PMID- 28509813
TI - Effect of Foeniculum vulgare Mill. (fennel) on menopausal symptoms in
postmenopausal women: a randomized, triple-blind, placebo-controlled trial.
AB - OBJECTIVE: Preliminary data suggest that Foeniculum vulgare (fennel) can be an
effective treatment for menopausal symptoms. This trial was designed to assess
the efficacy of fennel in the management of menopausal symptoms in postmenopausal
women. METHODS: In this triple-blind, placebo-controlled trial, 90 postmenopausal
women aged 45 to 60 years in Tehran were randomly assigned to treatment (n = 45)
or placebo (n = 45) groups. The participants received 8 weeks of treatment with
soft capsules containing 100 mg fennel or a placebo (2 per day for each group).
The participants were followed for 2 weeks postintervention to assess the
continuance of the effect of intervention. The Menopause Rating Scale (MRS)
questionnaire was used to assess changes in menopausal symptoms at baseline and
at 4, 8, and 10 weeks after onset of intervention. RESULTS: The groups recorded
similar mean scores on the MRS questionnaire before intervention. After
intervention, the treatment group showed a significant decrease in the mean MRS
score. The results of the Friedman test showed significant differences between
the mean score at baseline and those at 4, 8, and 10 weeks after onset of
intervention in the treatment group (P < 0.001), whereas there were no
significant differences in the placebo group. When the fennel and the placebo
groups were compared, the independent t test showed significant differences in
mean scores between groups at 4, 8, and 10 weeks (2 weeks postintervention; P <
0.001). CONCLUSIONS: Fennel is an effective and safe treatment to reduce
menopausal symptoms in postmenopausal women without serious side effects. More
clinical trials with larger populations are required to confirm this result.
PMID- 28509815
TI - Serum iron concentration is associated with subcortical deep gray matter iron
levels in multiple sclerosis patients.
AB - Iron deposition has been noted widely in the subcortical deep gray matter (SDGM)
of multiple sclerosis (MS) patients. Recent evidence suggests that serum iron may
cross the blood-brain barrier and might be associated with SDGM iron deposition.
The aim of the current study was to assess whether an iron-sensitive MRI measure
is related to serum iron concentrations. This was a retrospective, cross
sectional study of 22 MS patients and 24 healthy controls (HCs), group matched
for age and sex. Participants were imaged on a 1.5-T MRI scanner. High-resolution
T1-weighted images and susceptibility-weighted images were acquired for assessing
SDGM volumes and iron deposition within the SDGM, respectively. All participants
also had blood drawn for the measurement of serum iron concentrations. MS and HC
groups were compared with respect to SDGM tissue volumes and iron content.
Partial correlations, controlling for age, sex, and structural volume, were used
to assess the relationship between serum iron and SDGM iron content. MS patients
presented with significantly smaller SDGM tissue volumes of the caudate, globus
pallidus, putamen, and thalamus (all P<=0.0001). With respect to HCs, increased
iron content was observed for MS patients in the globus pallidus (P=0.009) only.
In MS patients only, there was a significant relationship between serum iron and
putaminal iron volume (partial r=0.449, P=0.041), whereas trends were evidenced
for the caudate (partial r=0.396, P=0.078) and the globus pallidus (partial
r=0.410, P=0.065). Serum iron content in MS patients may be related to SDGM iron
content. These results warrant confirmation in a larger study of MS patients.
PMID- 28509814
TI - Validity, cut-points, and minimally important differences for two hot flash
related daily interference scales.
AB - OBJECTIVES: To conduct psychometric analyses to condense the Hot Flash-Related
Daily Interference Scale (HFRDIS) into a shorter form termed the Hot Flash
Interference (HFI) scale; evaluate cut-points for both scales; and establish
minimally important differences (MIDs) for both scales. METHODS: We analyzed
baseline and postrandomization patient-reported data pooled across three
randomized trials aimed at reducing vasomotor symptoms (VMS) in 899 midlife
women. Trials were conducted across five MsFLASH clinical sites between July 2009
and October 2012. We eliminated HFRDIS items based on experts' content validity
ratings and confirmatory factor analysis, and evaluated cut-points and
established MIDs by mapping HFRDIS and HFI to other measures. RESULTS: The three
item HFI (interference with sleep, mood, and concentration) demonstrated strong
internal consistency (alphas of 0.830 and 0.856), showed good fit to the
unidimensional "hot flash interference factor," and strong convergent validity
with HFRDIS scores, diary VMS, and menopausal quality of life. For both scales,
cut-points of mild (0-3.9), moderate (4-6.9), and severe (7-10) interference were
associated with increasing diary VMS ratings, sleep, and anxiety. The average MID
was 1.66 for the HFRDIS and 2.34 for the HFI. CONCLUSIONS: The HFI is a brief
assessment of VMS interference and will be useful in busy clinics to standardize
VMS assessment or in research studies where response burden may be an issue. The
scale cut-points and MIDs should prove useful in targeting those most in need of
treatment, monitoring treatment response, and interpreting existing and future
research findings.
PMID- 28509816
TI - Variations in Health Insurance Policies Regarding Biologic Therapy Use in
Inflammatory Bowel Disease.
AB - BACKGROUND: The American Gastroenterological Association (AGA) has developed
guidelines for the management of ulcerative colitis and Crohn's disease (CD)
recommending anti-TNF therapy in moderate-severe disease. However, which drug is
used is often dictated by insurance company policies. We sought to determine the
insurance policy requirements prior to approval of biologic therapies. METHODS:
Using the National Association of Insurance Commissioners report of the top 125
insurance companies by market share in 2014, we reviewed the first 50 that had
online policies regarding anti-TNF and vedolizumab available. Policies were
reviewed for criteria needed for approval of anti-TNF or vedolizumab therapy, and
for compliance with the current AGA clinical pathway recommendations. RESULTS:
Ninety-eight percent of policies are inconsistent with the AGA ulcerative colitis
pathway and require step-wise drug failure before approval of an anti-TNF. Only
11% of the policies allowed starting vedolizumab without initial failures of an
anti-TNF agent, and 21% required the failure of two or more anti-TNF agents.
Ninety percent of the policies are inconsistent with AGA CD pathway and require
step-wise drug failure before approval of an anti-TNF. Seventy-four percent
allowed for initiating infliximab specifically for fistulizing CD. Twenty-eight
percent required failing of at least two or more drugs before starting anti-TNF.
Only 8% policies allowed starting vedolizumab without initial failures of an anti
TNF agent, and 28% required the failure of two anti-TNF agents. CONCLUSIONS: The
majority of the policies reviewed fail to adhere to the current AGA pathway
recommendations for ulcerative colitis and CD. Further interventions are needed
to better align policies with optimal evidence-based drug therapy.
PMID- 28509818
TI - Commentary on Variations in Health Insurance Policies Regarding Biological
Therapy Use in IBD and a Modified Delphi Process for the Development of Choosing
Wisely for IBD.
PMID- 28509817
TI - Modified Delphi Process for the Development of Choosing Wisely for Inflammatory
Bowel Disease.
AB - BACKGROUND AND AIMS: The prevalence and incidence of inflammatory bowel disease
(IBD) in North America is among the highest in the world and imparts substantial
direct and indirect medical costs. The Choosing Wisely Campaign was launched in
wide variety of medical specialties and disciplines to reduce unnecessary or
harmful tests or treatment interventions. METHODS: The Choosing Wisely list for
IBD was developed by the Canadian IBD Network for Research and Growth in Quality
Improvement (CINERGI) in collaboration with Crohn's and Colitis Canada (CCC) and
the Canadian Association of Gastroenterology (CAG). Using a modified Delphi
process, 5 recommendations were selected from an initial list of 30 statements at
a face-to-face consensus meeting. RESULTS: The 5 things physicians and patients
should question: (1) Don't use steroids (e.g., prednisone) for maintenance
therapy in IBD; (2) Don't use opioids long-term to manage abdominal pain in
inflammatory bowel disease (IBD); (3) Don't unnecessarily prolong the course of
intravenous corticosteroids in patients with acute severe ulcerative colitis (UC)
in the absence of clinical response; (4) Don't initiate or escalate long-term
medical therapies for the treatment of IBD based only on symptoms; and (5) Don't
use abdominal computed tomography (CT) scan to assess IBD in the acute setting
unless there is suspicion of a complication (obstruction, perforation, abscess)
or a non-IBD etiology for abdominal symptoms. CONCLUSIONS: The Choosing Wisely
recommendations will foster patient-physician discussions to optimize IBD
therapy, reduce adverse effects from testing and treatment, and reduce medical
expenditure.
PMID- 28509819
TI - Cortical and Physical Function after Mild Traumatic Brain Injury.
AB - PURPOSE: The aim of this study was to prospectively examine the association
between intracortical inhibition and functional recovery after mild traumatic
brain injury (mTBI). METHODS: Twenty individuals with mTBI and 20 matched control
participants were assessed using transcranial magnetic stimulation, the
Attentional Network Test, and gait analysis. Hierarchical linear modeling was
used to longitudinally examine potential differences between groups and
relationships in the pattern of recovery in cortical silent period (CSP)
duration, cognitive reaction time, and single- and dual-task walking speeds
across five testing time points. Individuals with mTBI were assessed within 72 h
of injury, and again at 1 wk, 2 wk, 1 month, and 2 months postinjury. After
initial testing, control participants followed a similar timeline. RESULTS: At
the 72-h time point, the group with mTBI had longer reaction time (b = -91.76, P
= 0.01), similar single-task walking speed (b = 0.055, P = 0.10), and slower dual
task walking speed (b = 0.10, P = 0.012) compared with control participants. The
CSP duration also tended to be longer in individuals with mTBI than controls at
the 72-h time point (b = -16.34, P = 0.062). The change is CSP duration over time
was not significantly associated with the change in reaction time (b = -0.19, P =
0.47), single-task walking speed (b = 0.0001, P = 0.53), or dual-task walking
speed (b < 0.001, P = 0.68). CONCLUSION: Although cognitive and motor functions
were significantly impaired in the mTBI group acutely after injury, levels of
intracortical inhibition were not associated with recovery in either functional
domain.
PMID- 28509820
TI - Impact of Preoperative Opioid Use on Total Knee Arthroplasty Outcomes.
AB - BACKGROUND: There is growing concern about the use of opioids prior to total knee
arthroplasty (TKA), and research has suggested that preoperative opioid use may
lead to worse pain outcomes following surgery. We evaluated the pain relief
achieved by TKA in patients who had and those who had not used opioids use before
the procedure. METHODS: We augmented data from a prospective cohort study of TKA
outcomes with opioid-use data abstracted from medical records. We collected
patient-reported outcomes and demographic data before and 6 months after TKA. We
used the Pain Catastrophizing Scale and the Western Ontario and McMaster
Universities Osteoarthritis Index (WOMAC) to quantify the pain experiences of
patients treated with TKA who had had a baseline score of >=20 on the WOMAC pain
scale (a 0 to 100-point scale, with 100 being the worst score), who provided
follow-up data, and who had not had another surgical procedure within the 2 years
prior to TKA. We built a propensity score for preoperative opioid use based on
the Pain Catastrophizing Scale score, comorbidities, and baseline pain. We used a
general linear model, adjusting for the propensity score and baseline pain, to
compare the change in the WOMAC pain score 6 months after TKA between persons who
had and those who had not used opioids before TKA. RESULTS: The cohort included
156 patients with a mean age of 65.7 years (standard deviation [SD] = 8.2 years)
and a mean body mass index (BMI) of 31.1 kg/m (SD = 6.1 kg/m); 62.2% were female.
Preoperatively, 36 patients (23%) had had at least 1 opioid prescription. The
mean baseline WOMAC pain score was 43.0 points (SD = 12.8) for the group that had
not used opioids before TKA and 46.9 points (SD = 15.7) for those who had used
opioids (p = 0.12). The mean preoperative Pain Catastrophizing Scale score was
greater among opioid users (15.5 compared with 10.7 points among non-users, p =
0.006). Adjusted analyses showed that the opioid group had a mean 6-month
reduction in the WOMAC pain score of 27.0 points (95% confidence interval [CI] =
22.7 to 31.3) compared with 33.6 points (95% CI = 31.4 to 35.9) in the non-opioid
group (p = 0.008). CONCLUSIONS: Patients who used opioids prior to TKA obtained
less pain relief from the operation. Clinicians should consider limiting pre-TKA
opioid prescriptions to optimize the benefits of TKA. LEVEL OF EVIDENCE:
Therapeutic Level III. See Instructions for Authors for a complete description of
levels of evidence.
PMID- 28509821
TI - Minimum Information for Studies Evaluating Biologics in Orthopaedics (MIBO):
Platelet-Rich Plasma and Mesenchymal Stem Cells.
AB - BACKGROUND: A comprehensive approach to the evaluation of biologic therapies for
musculoskeletal conditions is required to guide appropriate future use. Clinical
studies evaluating platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs)
are limited by inadequate reporting of scientific details critical to outcome. We
developed minimum reporting requirements for clinical studies evaluating PRP and
MSCs using Delphi consensus methods. METHODS: The need for consensus on the
minimum reporting requirements for studies evaluating biologics was identified at
the American Academy of Orthopaedic Surgeons/Orthopaedic Research Society
(AAOS/ORS) Biologic Treatments for Orthopaedic Injuries Symposium in 2015 and the
American Orthopaedic Society for Sports Medicine (AOSSM) Biologic Treatments for
Sports Injuries II Think Tank in 2015. A working group facilitated the
development of 2 expert consensus statements for PRP and MSCs using Delphi
techniques. Exhaustive lists of items that could be reported on by clinical
studies evaluating PRP or MSCs were generated by searching the published
literature and protocols. PRP and MSC expert groups, each made up of 24 invited
speakers at the AAOS and AOSSM symposia, were surveyed on 3 occasions to
establish consensus on the inclusion of each item within minimum reporting
guidelines. In addition to rating their agreement, the experts were encouraged to
propose further items or modifications. Predefined criteria were used to refine
item lists after each survey. Final lists were compiled into checklist statements
by the working group. RESULTS: For PRP, the working group identified 93
experimental information items from the literature. Twenty-three experts (96%)
completed 3 rounds of surveys. After 3 rounds, 58 items generated consensus with
>75% agreement and <5% disagreement. These items were compiled into a 23
statement checklist. For MSCs, 103 items were identified from the published
literature. Twenty-three experts (96%) completed 3 rounds of surveys. After 3
rounds, the 61 items for which consensus was reached were compiled into a 25
statement checklist. CONCLUSIONS: This study has established expert consensus on
the minimum reporting requirements for clinical studies evaluating PRP and MSCs.
CLINICAL RELEVANCE: These checklists provide specifications for the minimum
information that should be reported by clinical studies evaluating PRP or MSCs.
PMID- 28509822
TI - Fracture Prevention in the Orthopaedic Environment: Outcomes of a Coordinator
Based Fracture Liaison Service.
AB - BACKGROUND: Fracture liaison services focus on secondary fracture prevention by
identifying patients at risk for future fracture and initiating appropriate
evaluation, risk assessment, education, and therapeutic intervention. This study
describes key clinical outcomes including bone mineral densitometry, physician
assessment, and pharmacotherapy initiation in pharmacotherapy-naive patients
undergoing treatment for fragility fracture in a Canadian fracture liaison
service. METHODS: We determined rates of post-fracture investigation and
treatment for inpatients and outpatients with a fragility fracture seen in a
coordinator-based fracture liaison service at an urban university trauma
hospital. The program identified distal radial, proximal femoral, proximal
humeral, and vertebral fragility fractures in female patients >=40 years of age
and male patients >=50 years of age and provided education, bone mineral
densitometry, inpatient consultation or outpatient specialist or primary care
physician referral for bone health management, and documented patient follow-up.
RESULTS: The 2,191 patients with a fragility fracture were not taking anti
osteoporosis pharmacotherapy at the time of identification (862 inpatients and
1,329 outpatients). Eighty-four percent of inpatients and 85% of outpatients
completed a bone mineral densitometry as recommended. Fifty-two percent of
patients with proximal femoral fracture, 29% of patients with vertebral fracture,
26% of patients with proximal humeral fracture, and 20% of patients with distal
radial fracture had osteoporosis confirmed on the basis of a bone mineral
densitometry T-score of <=-2.5 at the femoral neck or L1 to L4. Eighty-five
percent of inpatients and 79% of outpatients referred for bone health management
were assessed by a specialist or primary care physician. Of the patients who
attended their appointments, 73% of inpatients and 52% of outpatients received a
prescription for anti-osteoporosis medication. CONCLUSIONS: A high rate of
education, evaluation, and pharmacological treatment, if indicated, can be
achieved through a coordinator-facilitated fracture liaison service program.
CLINICAL RELEVANCE: Fracture prevention programs are currently engaged in
establishing and modifying fracture liaison services in a quest for practical and
effective models. The program described in this article exemplifies a coordinator
based model that produced good outcomes.
PMID- 28509824
TI - Implant Survival After Minimally Invasive Anterior or Anterolateral Vs.
Conventional Posterior or Direct Lateral Approach: An Analysis of 21,860 Total
Hip Arthroplasties from the Norwegian Arthroplasty Register (2008 to 2013).
AB - BACKGROUND: Since 2008, there has been an increase in the use of minimally
invasive surgery (MIS) through an anterior or anterolateral approach for total
hip arthroplasty (THA) in Norway. We compared the MIS approaches with the
conventional posterior and direct lateral approaches in terms of revision rates
and risk of revision. METHODS: On the basis of data in the Norwegian Arthroplasty
Register, 21,860 THAs with an uncemented stem, performed between 2008 and 2013,
were identified and included in the cohort. Of these THAs, 2,017 were done
through an MIS anterior approach; 2,087, through an MIS anterolateral approach;
5,961, through a posterior approach; and 11,795, through a direct lateral
approach. Follow-up ended on December 31, 2015. Two and 5-year survival rates
were calculated using Kaplan-Meier survival analysis. Relative risk (RR) was
calculated using Cox regression analysis, with adjustment for age, sex, primary
diagnosis, American Society of Anesthesiologists (ASA) grade, femoral head size,
cup fixation, type of articulation, and duration of surgery and using 6 revision
end points based on cause: any cause, infection, dislocation, femoral fracture,
aseptic loosening, and other/unknown cause. The median duration of follow-up was
4.3 years. RESULTS: There were no significant differences among the surgical
approaches with regard to the 2 and 5-year survival rates or RR of revision due
to any cause. The RR of revision due to infection was 0.53 (95% confidence
interval [CI] = 0.36 to 0.80, p = 0.002) for the MIS anterior and anterolateral
approaches and 0.57 (95% CI = 0.40 to 0.80, p = 0.001) for the posterior approach
compared with the direct lateral approach. The RR of revision due to dislocation
was 2.1 (95% CI = 1.5 to 3.1, p < 0.001) for the posterior approach compared with
the direct lateral approach but no significant difference in risk was found when
the MIS anterior and anterolateral approaches were compared with the direct
lateral approach (RR = 0.71, 95% CI = 0.40 to 1.3, p = 0.25). CONCLUSIONS: The
revision rates and risk of revision associated with the MIS anterior and
anterolateral approaches were not increased compared with those of the
conventional posterior and direct lateral approaches. LEVEL OF EVIDENCE:
Therapeutic Level III. See Instructions for Authors for a complete description of
levels of evidence.
PMID- 28509823
TI - Progression of Fatty Muscle Degeneration in Atraumatic Rotator Cuff Tears.
AB - BACKGROUND: The purpose of this prospective study was to examine the progression
of fatty muscle degeneration over time in asymptomatic shoulders with
degenerative rotator cuff tears. METHODS: Subjects with an asymptomatic rotator
cuff tear in 1 shoulder and pain due to rotator cuff disease in the contralateral
shoulder were enrolled in a prospective cohort. Subjects were followed annually
with shoulder ultrasonography, which evaluated tear size, location, and fatty
muscle degeneration. Tears that were either full-thickness at enrollment or
progressed to a full-thickness defect during follow-up were examined. A minimum
follow-up of 2 years was necessary for eligibility. RESULTS: One hundred and
fifty-six shoulders with full-thickness rotator cuff tears were potentially
eligible. Seventy shoulders had measurable fatty muscle degeneration of at least
1 rotator cuff muscle at some time point. Patients with fatty muscle degeneration
in the shoulder were older than those without degeneration (mean, 65.8 years [95%
confidence interval (CI), 64.0 to 67.6 years] compared with 61.0 years [95% CI,
59.1 to 62.9 years]; p < 0.05), and the median size of the tears at baseline was
larger in shoulders with degeneration than in shoulders that did not develop
degeneration (13 and 10 mm wide, respectively, and 13 and 10 mm long; p < 0.05).
Tears with fatty muscle degeneration were more likely to have enlarged during
follow-up than were tears that never developed muscle degeneration (79% compared
with 58%; odds ratio, 2.64 [95% CI, 1.29 to 5.39]; p < 0.05). Progression of
fatty muscle degeneration occurred more frequently in shoulders with tears that
had enlarged (43%; 45 of 105) than in shoulders with tears that had not enlarged
(20%; 10 of 51; p < 0.05). Additionally, tears with enlargement and progression
of muscle degeneration were more likely to extend into the anterior supraspinatus
than were those without progression (53% and 17%, respectively; p < 0.05);
however, this relationship was lost when controlling for tear size (p = 0.56).
The median time from tear enlargement to progression of fatty muscle degeneration
was 1.0 year (range, -2.0 to 6.9 years) for the supraspinatus and 1.1 years
(range, -1.8 to 8.5 years) for the infraspinatus muscle (p = 0.98). CONCLUSIONS:
Progression of fatty muscle degeneration is more common in tears that are larger
at baseline, enlarge over time, and undergo a larger magnitude of enlargement.
Our study findings also suggest that an often rapid progression of muscle
degeneration occurs in relation to a clinically relevant increase in tear size in
some degenerative cuff tears. LEVEL OF EVIDENCE: Prognostic Level II. See
Instructions for Authors for a complete description of levels of evidence.
PMID- 28509825
TI - Vascularized Pedicle Bone-Grafting from the Cuboid for Talar Osteonecrosis:
Results of a Novel Salvage Procedure.
AB - BACKGROUND: Osteonecrosis of the talar body represents a complex clinical
challenge with treatment options currently limited to core decompression,
vascularized and nonvascularized bone-grafting, total talar replacement, and
hindfoot arthrodesis. Vascularized pedicle bone-grafting from the cuboid to the
talus is a potential alternative to contemporary operative options for
replacement of necrotic talar tissue with viable bone. We aimed to analyze
functional and radiographic outcomes of vascularized pedicle bone-grafting from
the cuboid for the treatment of talar osteonecrosis in a consecutive series of
patients spanning a 12-year period. METHODS: Patients with osteonecrosis of the
talar body and dome who underwent vascularized pedicle bone-grafting from the
cuboid to the talus at our institution between 2003 and 2014 were retrospectively
identified. All patients had preoperative radiographs and magnetic resonance
imaging (MRI) scans and were monitored postoperatively with serial radiographs
and MRI. For generic health-related quality-of-life (HRQoL) assessment, patients
were given the preoperative Medical Outcomes Study Short Form-12 (SF-12) and
postoperative 36-Item Short Form (SF-36) from which Physical Component Summary
(PCS) and Mental Component Summary (MCS) scores were derived and compared before
and after surgery. RESULTS: Thirteen patients were identified and sequentially
followed for 2 to 12 years (mean, 6 years). Two patients had failure of treatment
and subsequently underwent total ankle replacement, 1 patient had arthroscopic
debridement for soft-tissue impingement, and no other patient required secondary
surgery. The average PCS score (and standard deviation) significantly improved by
23.3 +/- 18.9 points with surgery (p = 0.006), and the average MCS score
significantly increased by 39.4 +/- 10.1 points (p < 0.001). CONCLUSIONS: HRQoL
outcomes suggest that vascularized pedicle bone-grafting from the cuboid combined
with bracing for 1 year may be a viable treatment option for osteonecrosis of the
talus that provides good pain relief and improved physical function without
necessitating a secondary procedure for the majority of patients. LEVEL OF
EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete
description of levels of evidence.
PMID- 28509826
TI - Sclerostin Antibody Treatment Enhances Rotator Cuff Tendon-to-Bone Healing in an
Animal Model.
AB - BACKGROUND: Rotator cuff tears are a common source of pain and disability, and
poor healing after repair leads to high retear rates. Bone loss in the humeral
head before and after repair has been associated with poor healing. The purpose
of the current study was to mitigate bone loss near the repaired cuff and improve
healing outcomes. METHODS: Sclerostin antibody (Scl-Ab) treatment, previously
shown to increase bone formation and strength in the setting of osteoporosis, was
used in the current study to address bone loss and enhance rotator cuff healing
in an animal model. Scl-Ab was administered subcutaneously at the time of rotator
cuff repair and every 2 weeks until the animals were sacrificed. The effect of
Scl-Ab treatment was evaluated after 2, 4, and 8 weeks of healing, using bone
morphometric analysis, biomechanical evaluation, histological analysis, and gene
expression outcomes. RESULTS: Injury and repair led to a reduction in bone
mineral density after 2 and 4 weeks of healing in the control and Scl-Ab
treatment groups. After 8 weeks of healing, animals receiving Scl-Ab treatment
had 30% greater bone mineral density than the controls. A decrease in
biomechanical properties was observed in both groups after 4 weeks of healing
compared with healthy tendon-to-bone attachments. After 8 weeks of healing, Scl
Ab-treated animals had improved strength (38%) and stiffness (43%) compared with
control animals. Histological assessment showed that Scl-Ab promoted better
integration of tendon and bone by 8 weeks of healing. Scl-Ab had significant
effects on gene expression in bone, indicative of enhanced bone formation, and no
effect on the expression of genes in tendon. CONCLUSIONS: This study provides
evidence that Scl-Ab treatment improves tendon-to-bone healing at the rotator
cuff by increasing attachment-site bone mineral density, leading to improved
biomechanical properties. CLINICAL RELEVANCE: Scl-Ab treatment may improve
outcomes after rotator cuff repair.
PMID- 28509829
TI - In Total Knee Arthroplasty, Patient-Matched Positioning Guides and Conventional
Instruments Did Not Differ in Terms of Clinical Outcomes or Complications at Two
Years.
PMID- 28509827
TI - Leptin Elevation as a Risk Factor for Slipped Capital Femoral Epiphysis
Independent of Obesity Status.
AB - BACKGROUND: Slipped capital femoral epiphysis (SCFE) is strongly associated with
childhood obesity, yet the prevalence of obesity is orders of magnitude greater
than the prevalence of SCFE. Therefore, it is hypothesized that obesity is not,
by itself, a sufficient condition for SCFE, but rather one component of a
multifactorial process requiring preexisting physeal pathology. Leptin elevation
is seen to varying degrees in patients with obesity, and as leptin has been shown
to cause physeal pathology similar to the changes seen in SCFE, we propose that
leptin may be a factor distinguishing between patients with SCFE and equally
obese children without hip abnormalities. METHODS: Serum leptin levels were
obtained from 40 patients with SCFE and 30 control patients with approximate body
mass index (BMI) matching. BMI percentiles were calculated according to Centers
for Disease Control and Prevention population data by patient age and sex.
Patients were compared by demographic characteristics, leptin levels, odds of
leptin elevation, and odds of SCFE. RESULTS: The odds of developing SCFE was
increased by an odds ratio of 4.9 (95% confidence interval [CI], 1.31 to 18.48; p
< 0.02) in patients with elevated leptin levels, regardless of obesity status,
sex, and race. When grouping patients by their obesity status, non-obese patients
with SCFE showed elevated median leptin levels at 5.8 ng/mL compared with non
obese controls at 1.7 ng/mL (p = 0.006). Similarly, obese patients with SCFE
showed elevated median leptin levels at 17.9 ng/mL compared with equally obese
controls at 10.5 ng/mL (p = 0.039). Serum leptin levels increased in association
with obesity (p < 0.001), with an increase in leptin of 0.17 ng/mL (95% CI, 0.07
to 0.27 ng/mL) per BMI percentile point. CONCLUSIONS: To our knowledge, this
study is the first to clinically demonstrate an association between elevated
serum leptin levels and SCFE, regardless of BMI. This adds to existing literature
suggesting that SCFE is a multifactorial process and that leptin levels may have
profound physiological effects on the development of various disease states.
Despite a strong association with adiposity, leptin levels vary between patients
of equal BMI and may be a vital resource in prognostication of future obesity
related comorbidities. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions
for Authors for a complete description of levels of evidence.
PMID- 28509828
TI - Modular Fluted Tapered Stems in Aseptic Revision Total Hip Arthroplasty.
AB - BACKGROUND: Modular fluted tapered stems have become the most commonly employed
category of femoral component in revision hip arthroplasty in North America as a
result of favorable early results and simplicity of use. Despite wide adoption,
the majority of published data are limited to relatively small series with modest
follow-up. The goal of the current study was to determine the success rate and
factors associated with success, failure, and complications of the use of modular
fluted tapered stems in aseptic revision total hip arthroplasties (THAs) in a
large patient cohort. METHODS: We identified 519 aseptic femoral revisions during
which a modular fluted tapered stem was utilized. Clinical outcomes, Kaplan-Meier
survivorship, radiographic outcomes, and complications were assessed. The mean
age at revision arthroplasty was 70 years, the mean body mass index (BMI) was 29
kg/m, and the mean duration of follow-up was 4.5 years (range, 2 to 14 years).
RESULTS: The mean Harris hip score (HHS) improved significantly from 51 points
preoperatively to 76 points at 2 years (p < 0.001). This improvement was
maintained at the last follow-up evaluation (mean HHS = 75 points). At the time
of the most recent follow-up, 16 femoral revisions had been performed: 6 because
of aseptic loosening, 4 because of infection, 3 because of instability, 2 because
of periprosthetic fracture, and 1 because of stem fracture. The 10-year
survivorship was 96% with revision for any reason as the end point and 90% with
any reoperation as the end point. Of the patients who were alive and had not
undergone revision at the time of final follow-up, 12 had stem subsidence but all
but 1 of these stems had stabilized after subsiding. Postoperative complications
were noted in 12% of the cases. Repeat revision due to femoral component
loosening was not correlated with the preoperative bone-loss category or patient
demographic factors. CONCLUSIONS: In this large series, femoral revision with a
modular fluted tapered stem provided a high rate of osseointegration and
sustained improvement in clinical scores at the time of the last follow-up. There
was also a high rate of successful implant fixation across all categories of
preoperative bone loss and an acceptable rate of complications. LEVEL OF
EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete
description of levels of evidence.
PMID- 28509830
TI - Using Small Intestine Submucosa to Augment Repair of Moderate to Large Rotator
Cuff Tears Did Not Reduce Repair Failures.
PMID- 28509831
TI - Fibular Nailing Did Not Differ from Standard Open Reduction and Internal Fixation
for Unstable Ankle Fractures in Elderly Patients.
PMID- 28509832
TI - What's New in Sports Medicine.
PMID- 28509833
TI - Minimum Five-Year Outcomes with Porous Tantalum Acetabular Cup and Augment
Construct in Complex Revision Total Hip Arthroplasty.
AB - BACKGROUND: The use of a trabecular metal revision shell with metal augmentation
to fill segmental or irregular defects during complex revision hip arthroplasty
has been shown to provide good short-term results in prior published series.
Longer-term results of the several cup-augment constructs used clinically are not
known. The objective of this study was to report, with minimum 5-year
radiographic and clinical follow-up, the outcome of these various constructs in
revision total hip arthroplasty. METHODS: Eighty-four patients (85 hips)
underwent revision total hip arthroplasty with use of porous tantalum augments
between 2000 and 2007 at a single institution and were retrospectively reviewed.
Fifty-seven of the patients (58 hips) had clinical and radiographic follow-up at
a minimum of 5 years. At the time of revision, the majority of the hips had
acetabular defects classified as Paprosky Type 3A (28 of 58, 48%) or Type 3B (22
of 58, 38%). Eleven (19%) of the hips also had preoperative pelvic discontinuity.
All hips were assessed clinically at a minimum of 5 years with use of the Mayo
hip score. Postoperative radiographs were reviewed for implant stability, the
presence and location of radiolucent lines and healing of the discontinuity if
present. RESULTS: In 2 (3%) of the 58 hips, the constructs failed because of
aseptic loosening of the acetabular component and re-revision was indicated. Six
(10%) of the 58 hips demonstrated a radiolucent line between the trabecular metal
shell and bone in DeLee and Charnley zone 3. In 1 hip that underwent re-revision
and in 5 of the 6 hips with a zone-3 radiolucency, a pelvic discontinuity was
present at the time of the index revision. The mean preoperative Mayo hip score
was 35.7, which improved to 61.9 at 3 months and was 61.7 at the minimum 5-year
follow-up. CONCLUSIONS: With failure defined as aseptic loosening requiring
repeat revision surgery, this cohort demonstrated 97% survivorship and maintained
satisfactory hip function at the minimum 5 years after the index revision
surgery. Six of the 11 hips with preoperative pelvic discontinuity either failed
or developed a radiolucency in zone 3 and are considered at risk for future
revision. Pelvic discontinuity should prompt consideration of the addition of
adjunctive fixation or the use of alternative techniques. LEVEL OF EVIDENCE:
Therapeutic Level IV. See Instructions for Authors for a complete description of
levels of evidence.
PMID- 28509834
TI - Decisions and Incisions: A Value-Driven Practice Framework for Academic Surgeons.
PMID- 28509835
TI - Changes by the Accreditation Council for Graduate Medical Education: Success or
Failure?: An AOA Critical Issues Symposium.
AB - The Accreditation Council for Graduate Medical Education has introduced far
reaching changes to the educational requirements for postgraduate trainees over
the past 15 years. These steps were taken to improve the quality of education and
to enhance patient safety. This symposium will explore the design and
implementation of these changes and determine if they are succeeding.
PMID- 28509836
TI - Make No Bones About It-Rotator Cuff Repair Healing Is Not Just About the Tendon:
Commentary on an article by Shivam A. Shah, PhD, et al.: "Sclerostin Antibody
Treatment Enhances Rotator Cuff Tendon-to-Bone Healing in an Animal Model".
PMID- 28509837
TI - The End of the Road for Idiopathic Slipped Capital Femoral Epiphysis?: Commentary
on an article by Schuyler J. Halverson, MD, MS, et al.: "Leptin Elevation as a
Risk Factor for Slipped Capital Femoral Epiphysis Independent of Obesity Status".
PMID- 28509838
TI - Long-Term Effect of a Stigma-Reduction Educational Intervention for Physician
Assistants.
AB - PURPOSE: Stigma towards people with substance use disorders is a common
phenomenon with far reaching effects. This study evaluated the long-term effect
of using an educational intervention on the attitudes of physician assistant
students. METHODS: Physician assistant students received a one-week educational
intervention focused on substance abuse. Changes in student attitudes were
measured one year later using the Attitude to Mental Health Questionnaire (AMIQ).
RESULTS: Significant and sustained improvement was noted in attitudes in the AMIQ
score for the opiate use disorder vignette; no significant change was noted in
the alcohol use disorder vignette. CONCLUSIONS: The persistence of improved
attitudes (although they remained negative) in study participants towards people
with opiate use disorders is a cautiously encouraging finding. Educational
interventions can have a sustained effect on stigma reduction, but much more work
on the etiology of these implicit and explicit beliefs is needed to inform robust
future interventions.
PMID- 28509839
TI - Autonomy, Authenticity, and Deferred Decision Making: The Practical Application
of Abstract Concepts for Physician Assistants.
PMID- 28509840
TI - Negotiating on Behalf of Your Program.
PMID- 28509841
TI - Simultaneous Wireless Power Transfer and Secure Multicasting in Cooperative
Decode-and-Forward Relay Networks.
AB - In this paper, we investigate simultaneous wireless power transfer and secure
multicasting via cooperative decode-and-forward (DF) relays in the presence of
multiple energy receivers and eavesdroppers. Two scenarios are considered under a
total power budget: maximizing the minimum harvested energy among the energy
receivers under a multicast secrecy rate constraint; and maximizing the multicast
secrecy rate under a minimum harvested energy constraint. For both scenarios, we
solve the transmit power allocation and relay beamformer design problems by using
semidefinite relaxation and bisection technique. We present numerical results to
analyze the energy harvesting and secure multicasting performances in cooperative
DF relay networks.
PMID- 28509843
TI - Modeling the Footprint and Equivalent Radiance Transfer Path Length for Tower
Based Hemispherical Observations of Chlorophyll Fluorescence.
AB - The measurement of solar-induced chlorophyll fluorescence (SIF) is a new tool for
estimating gross primary production (GPP). Continuous tower-based spectral
observations together with flux measurements are an efficient way of linking the
SIF to the GPP. Compared to conical observations, hemispherical observations made
with cosine-corrected foreoptic have a much larger field of view and can better
match the footprint of the tower-based flux measurements. However, estimating the
equivalent radiation transfer path length (ERTPL) for hemispherical observations
is more complex than for conical observations and this is a key problem that
needs to be addressed before accurate retrieval of SIF can be made. In this
paper, we first modeled the footprint of hemispherical spectral measurements and
found that, under convective conditions with light winds, 90% of the total
radiation came from an FOV of width 72 degrees , which in turn covered 75.68% of
the source area of the flux measurements. In contrast, conical spectral
observations covered only 1.93% of the flux footprint. Secondly, using
theoretical considerations, we modeled the ERTPL of the hemispherical spectral
observations made with cosine-corrected foreoptic and found that the ERTPL was
approximately equal to twice the sensor height above the canopy. Finally, the
modeled ERTPL was evaluated using a simulated dataset. The ERTPL calculated using
the simulated data was about 1.89 times the sensor's height above the target
surface, which was quite close to the results for the modeled ERTPL. Furthermore,
the SIF retrieved from atmospherically corrected spectra using the modeled ERTPL
fitted well with the reference values, giving a relative root mean square error
of 18.22%. These results show that the modeled ERTPL was reasonable and that this
method is applicable to tower-based hemispherical observations of SIF.
PMID- 28509842
TI - Molecular Epidemiology of Methicillin-Resistant and Methicillin-Susceptible
Staphylococcus aureus in the Ovine Dairy Chain and in Farm-Related Humans.
AB - Staphylococcus aureus is a major cause of clinical infections in humans and its
enterotoxins cause foodborne disease. In the present study, we tested a total of
51 isolates of S. aureus from small-ruminant dairy farms with artisan dairy
facilities, all located in Latium, Italy. The farms have a known history of a
high prevalence of methicillin-resistant S. aureus (MRSA). Most of the MRSA
isolates (27 of 51) belonged to spa-type t127 (43.1%), followed by t2678 (3.9%),
t044 (2%), t1166 (2%), and t1773 (2%). PFGE performed on mecA positive strains
identified one cluster (>= 80% of similarity), comprising 22 MRSA. Nine of twenty
two MRSA isolates were assigned human host origin, and 13 isolates did not belong
to a specific host. During the characterization study, one strain isolated from
bulk tank milk samples harbored the pvl gene; the strain was not enterotoxigenic
with a non-specific host according to the biotyping scheme, highlighting the
possible emerging risk of transmission of bacterial virulence factors by foods,
the environment, and foodhandlers. These findings stress the importance of
hygienic measures at all processing steps of the food production chain and
underline that monitoring for the presence of MRSA throughout the food chain is
essential for public health.
PMID- 28509844
TI - Influence of Nano-Hydroxyapatite on the Metal Bioavailability, Plant Metal
Accumulation and Root Exudates of Ryegrass for Phytoremediation in Lead-Polluted
Soil.
AB - Lead is recognized as one of the most widespread toxic metal contaminants and
pervasive environmental health concerns in the environment. In this paper, the
effects of nano-hydroxyapatite (NHAP) on remediation in artificially Pb
contaminated soils and ryegrass were studied in a pot experiment. The addition of
NHAP decreased the water- and acid-soluble, exchangeable, and reducible fractions
of Pb, extracted using the Community Bureau of Reference (BCR) method, whilst
greatly increasing the residual fraction of Pb. Oxidizable Pb was increased
slightly. No significant increase in soil pH was caused by the application of
NHAP. Compared to conditions without NHAP, the addition of NHAP decreased the Pb
content in ryegrass shoots and roots by 13.19-20.3% and 2.86-21.1%, respectively.
Therefore, the application of NHAP reduced the mobility and bioavailability of Pb
in the soil. In addition, the application of NHAP improved the fresh weight of
shoots and roots, and promoted the growth of ryegrass. NHAP played a positive
role in stimulating ryegrass to secrete tartaric acid.
PMID- 28509847
TI - A Robust Method to Detect BeiDou Navigation Satellite System Orbit
Maneuvering/Anomalies and Its Applications to Precise Orbit Determination.
AB - The failure to detect anomalies and maneuvering of the orbits of navigation
satellite sensors will deteriorate the performance of positioning and orbit
determination. Motivated by the influence of the frequent maneuvering of BDS GEO
and IGSO satellites, this paper analyzes the limitations of existing methods,
where BDS orbit maneuvering and anomalies can be detected, and develops a method
to solve this problem based on the RMS model of orbit mutual differences proposed
in this paper. The performance of this method was assessed by comparison with the
health flag of broadcast ephemeris, precise orbit products of GFZ, the O-C values
of a GNSS station and a conventional method. The results show that the
performance of the method developed in this paper is better than that of the
conventional method when the periodicity and trend items are obvious. Meanwhile,
three additional verification results show that the method developed in this
paper can find error information in the merged broadcast ephemeris provided by
iGMAS. Furthermore, from the testing results, it can be seen that the detection
of anomaly and maneuvering items do not affect each other based on the robust
thresholds constructed in this paper. In addition, the precise orbit of the
maneuvering satellites can be determined under the circumstances that the
maneuver information detected in this paper is used, and the root mean square
(RMS) of orbit overlap comparison for GEO-03/IGSO-03 in Radial, Along, Cross, 1D
RMS are 0.7614/0.4460 m, 1.8901/0.3687 m, 0.3392/0.2069 m, 2.0657/0.6145 m,
respectively.
PMID- 28509845
TI - Metabolic Portraits of Breast Cancer by HR MAS MR Spectroscopy of Intact Tissue
Samples.
AB - Despite progress in early detection and therapeutic strategies, breast cancer
remains the second leading cause of cancer-related death among women globally.
Due to the heterogeneity and complexity of tumor biology, breast cancer patients
with similar diagnosis might have different prognosis and response to treatment.
Thus, deeper understanding of individual tumor properties is necessary. Cancer
cells must be able to convert nutrients to biomass while maintaining energy
production, which requires reprogramming of central metabolic processes in the
cells. This phenomenon is increasingly recognized as a potential target for
treatment, but also as a source for biomarkers that can be used for prognosis,
risk stratification and therapy monitoring. Magnetic resonance (MR) metabolomics
is a widely used approach in translational research, aiming to identify
clinically relevant metabolic biomarkers or generate novel understanding of the
molecular biology in tumors. Ex vivo proton high-resolution magic angle spinning
(HR MAS) MR spectroscopy is widely used to study central metabolic processes in a
non-destructive manner. Here we review the current status for HR MAS MR
spectroscopy findings in breast cancer in relation to glucose, amino acid and
choline metabolism.
PMID- 28509846
TI - A New Ergosterol Analog, a New Bis-Anthraquinone and Anti-Obesity Activity of
Anthraquinones from the Marine Sponge-Associated Fungus Talaromyces stipitatus
KUFA 0207.
AB - A new ergosterol analog, talarosterone (1) and a new bis-anthraquinone derivative
(3) were isolated, together with ten known compounds including palmitic acid,
ergosta-4,6,8(14),22-tetraen-3-one, ergosterol-5,8-endoperoxide, cyathisterone
(2), emodin (4a), questinol (4b), citreorosein (4c), fallacinol (4d), rheoemodin
(4e) and secalonic acid A (5), from the ethyl acetate extract of the culture of
the marine sponge-associated fungus Talaromyces stipitatus KUFA 0207. The
structures of the new compounds were established based on extensive 1D and 2D
spectral analysis, and in the case of talarosterone (1), the absolute
configurations of its stereogenic carbons were determined by X-ray
crystallographic analysis. The structure and stereochemistry of cyathisterone (2)
was also confirmed by X-ray analysis. The anthraquinones 4a-e and secalonic acid
A (5) were tested for their anti-obesity activity using the zebrafish Nile red
assay. Only citreorosein (4c) and questinol (4b) exhibited significant anti
obesity activity, while emodin (4a) and secalonic acid A (5) caused toxicity
(death) for all exposed zebrafish larvae after 24 h.
PMID- 28509848
TI - Biosensor Based on Tyrosinase Immobilized on Graphene-Decorated Gold
Nanoparticle/Chitosan for Phenolic Detection in Aqueous.
AB - In this research work, electrochemical biosensor was fabricated based on
immobilization of tyrosinase onto graphene-decorated gold nanoparticle/chitosan
(Gr-Au-Chit/Tyr) nanocomposite-modified screen-printed carbon electrode (SPCE)
for the detection of phenolic compounds. The nanocomposite film was constructed
via solution casting method. The electrocatalytic activity of the proposed
biosensor for phenol detection was studied using differential pulse voltammetry
(DPV) and cyclic voltammetry (CV). Experimental parameters such as pH buffer,
enzyme concentration, ratio of Gr-Au-Chit, accumulation time and potential were
optimized. The biosensor shows linearity towards phenol in the concentration
range from 0.05 to 15 MUM with sensitivity of 0.624 MUA/MUM and the limit of
detection (LOD) of 0.016 MUM (S/N = 3). The proposed sensor also depicts good
reproducibility, selectivity and stability for at least one month. The biosensor
was compared with high-performance liquid chromatography (HPLC) method for the
detection of phenol spiked in real water samples and the result is in good
agreement and comparable.
PMID- 28509849
TI - Low Duty-Cycling MAC Protocol for Low Data-Rate Medical Wireless Body Area
Networks.
AB - Wireless body area networks (WBANs) are severely energy constrained, and how to
improve the energy efficiency so as to prolong the network lifetime as long as
possible is one of the most important goals of WBAN research. Low data-rate WBANs
are promising to cut down the energy consumption and extend the network lifetime.
Considering the characteristics and demands of low data-rate WBANs, a low duty
cycling medium access control (MAC) protocol is specially designed for this kind
of WBAN in this paper. Longer superframes are exploited to cut down the energy
consumed on the transmissions and receptions of redundant beacon frames.
Insertion time slots are embedded into the inactive part of a superframe to
deliver the frames and satisfy the quality of service (QoS) requirements. The
number of the data subsections in an insertion time slot can be adaptively
adjusted so as to accommodate low data-rate WBANs with different traffic.
Simulation results show that the proposed MAC protocol performs well under the
condition of low data-rate monitoring traffic.
PMID- 28509850
TI - Accessing Mefenamic Acid Form II through High-Pressure Recrystallisation.
AB - High-pressure crystallisation has been successfully used as an alternative
technique to prepare Form II of a non-steroidal anti-inflammatory drug, mefenamic
acid (MA). A single crystal of Form II, denoted as high-pressure Form II, was
grown at 0.3 GPa from an ethanolic solution by using a diamond anvil cell. A
comparison of the crystal structures shows that the efficient packing of
molecules in Form II was enabled by the structural flexibility of MA molecules.
Compression studies performed on a single crystal of Form I resulted in a 14%
decrease of unit cell volume up to 2.5 GPa. No phase transition was observed up
to this pressure. A reconstructive phase transition is required to induce
conformational changes in the structure, which was confirmed by the results of
crystallisation at high pressure.
PMID- 28509851
TI - Development of a Flow Injection Based High Frequency Dual Channel Quartz Crystal
Microbalance.
AB - When the quartz crystal microbalance (QCM) is used in liquid for adsorption or
desorption monitoring based bio- or chemical sensing applications, the frequency
shift is not only determined by the surface mass change, but also by the change
of liquid characteristics, such as density and viscosity, which are greatly
affected by the liquid environmental temperature. A monolithic dual-channel QCM
is designed and fabricated by arranging two QCM resonators on one single chip for
cancelling the fluctuation induced by environmental factors. In actual
applications, one QCM works as a specific sensor by modifying with functional
membranes and the other acts as a reference, only measuring the liquid property.
The dual-channel QCM is designed with an inverted-mesa structure, aiming to
realize a high frequency miniaturized chip and suppress the frequency
interference between the neighbored QCM resonators. The key problem of dual
channel QCMs is the interference between two channels, which is influenced by the
distance of adjacent resonators. The diameter of the reference electrode has been
designed into several values in order to find the optimal parameter. Experimental
results demonstrated that the two QCMs could vibrate individually and the output
frequency stability and drift can be greatly improved with the aid of the
reference QCM.
PMID- 28509853
TI - Predictors of Caregiver Burden among Mothers of Children with Chronic Conditions.
AB - OBJECTIVE: The complex medical regimens of children and adolescents with chronic
conditions can have a significant impact on families and households. Caregivers
may experience burden, which can lead to negative health consequences and poor
quality of life. The objective of this study was to determine child-related
predictors and risk factors for caregiver burden among parents of children with
chronic conditions. METHODS: We distributed an institutional review board (IRB)
approved, online cross-sectional survey to parents of children who attended the
Victory Junction therapeutic camp. Parents provided information on child
demographics, disease characteristics, and healthcare utilization. Parents also
answered the adapted Zarit Burden Interview, which measured caregiver burden.
Children completed scales about self-management and self-efficacy. Linear
regression analyses determined how children's disease characteristics, health
utilization, and self-management skills were associated with caregiver burden.
RESULTS: We enrolled 150 mother-child dyads. The mean age of child participants
was 12.23 years (+/-2.5), with an age range of 6 to 16 years. It was determined
that children's number of medicines and injections (beta = 0.161, p = 0.047), a
diagnosis of attention-deficit/hyperactivity disorder (ADHD) in addition to the
primary medical condition (beta = 0.216, p = 0.008), frequent visits with a
primary care provider (PCP) (beta = 0.209, p = 0.026) and emergency room (ER)
visits (beta = 0.197, p = 0.038), and lower child self-efficacy (beta = -0.241, p
= 0.041) were predictors of increased caregiver burden. CONCLUSIONS: We
identified risk factors for caregiver burden among mothers. Future studies should
explore additional child-related characteristics as they relate to caregiver
burden, and should determine if interventions for mothers of children with
chronic conditions can lead to positive outcomes.
PMID- 28509852
TI - Inhaled Antibiotic Therapy in Chronic Respiratory Diseases.
AB - The management of patients with chronic respiratory diseases affected by
difficult to treat infections has become a challenge in clinical practice.
Conditions such as cystic fibrosis (CF) and non-CF bronchiectasis require
extensive treatment strategies to deal with multidrug resistant pathogens that
include Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus,
Burkholderia species and non-tuberculous Mycobacteria (NTM). These challenges
prompted scientists to deliver antimicrobial agents through the pulmonary system
by using inhaled, aerosolized or nebulized antibiotics. Subsequent research
advances focused on the development of antibiotic agents able to achieve high
tissue concentrations capable of reducing the bacterial load of difficult-to
treat organisms in hosts with chronic respiratory conditions. In this review, we
focus on the evidence regarding the use of antibiotic therapies administered
through the respiratory system via inhalation, nebulization or aerosolization,
specifically in patients with chronic respiratory diseases that include CF, non
CF bronchiectasis and NTM. However, further research is required to address the
potential benefits, mechanisms of action and applications of inhaled antibiotics
for the management of difficult-to-treat infections in patients with chronic
respiratory diseases.
PMID- 28509854
TI - The Phenolic Fraction of Mentha haplocalyx and Its Constituent Linarin Ameliorate
Inflammatory Response through Inactivation of NF-kappaB and MAPKs in
Lipopolysaccharide-Induced RAW264.7 Cells.
AB - Mentha haplocalyx has been widely used for its flavoring and medicinal properties
and as a traditional Chinese medicine with its anti-inflammation properties. The
present study was designed to investigate the anti-inflammatory effects and
potential molecular mechanisms of the phenolic fraction of M. haplocalyx (MHP)
and its constituent linarin in lipopolysaccharide (LPS)-induced RAW264.7 cells.
The high-performance liquid chromatography coupled with linear ion trap-orbitrap
mass spectrometry (HPLC-LTQ-Orbitrap MS) was used to analyze the chemical
composition of MHP. Using the enzyme-linked immunosorbent assay (ELISA) and
quantitative realtime polymerase chain reaction (qRT-PCR), the expression of pro
inflammatory meditators and cytokines was measured at the transcriptional and
translational levels. Western blot analysis was used to further investigate
changes in the nuclear factor kappa B (NF-kappaB), mitogen-activated protein
kinase (MAPK), and Akt signaling pathways. Fourteen phenolic constituents were
identified from MHP based on the data of the mass spectrometry (MS)/MS analysis.
MHP and linarin decreased the production of NO, tumor necrosis factor-alpha (TNF
alpha), interlenkin-1beta (IL-1beta), and IL-6. The messenger ribonucleic acid
(mRNA) expression levels of inducible NO synthase (iNOS), TNF-alpha, IL-1beta,
and IL-6 were also suppressed by MHP and linarin. Further investigation showed
that MHP and linarin down-regulated LPS-induced phosphorylation content of NF
kappaB p65, inhibitor kappa B alpha (IkappaBalpha), extracellular signal
regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38. However, MHP
and linarin showed no inhibitory effect on the phosphorylated Akt. These results
suggested that MHP and linarin exerted a potent inhibitory effect on pro
inflammatory meditator and cytokines production via the inactivation of NF-kappaB
and MAPKs, and they may serve as potential modulatory agents for the prevention
and treatment of inflammatory diseases.
PMID- 28509855
TI - The Hypnotic, Anxiolytic, and Antinociceptive Profile of a Novel u-Opioid
Agonist.
AB - 5'-4-Alkyl/aryl-1H-1,2,3-triazole derivatives PILAB 1-12 were synthesized and a
pharmacological screening of these derivatives was performed to identify a
possible effect on the Central Nervous System (CNS) and to explore the associated
mechanisms of action. The mice received a peritoneal injection (100 umol/kg) of
each of the 12 PILAB derivatives 10 min prior to the injection of pentobarbital
and the mean hypnosis times were recorded. The mean hypnosis time increased for
the mice treated with PILAB 8, which was prevented when mice were administered
CTOP, a u-opioid antagonist. Locomotor and motor activities were not affected by
PILAB 8. The anxiolytic effect of PILAB 8 was evaluated next in an elevated-plus
maze apparatus. PILAB 8 and midazolam increased a percentage of entries and spent
time in the open arms of the apparatus compared with the control group.
Conversely, a decrease in the percentages of entries and time spent in the closed
arms were observed. Pretreatment with naloxone, a non-specific opioid antagonist,
prior to administration of PILAB 8 exhibited a reverted anxiolytic effect. PILAB
8 exhibited antinociceptive activity in the hot plate test, and reduced
reactivity to formalin in the neurogenic and the inflammatory phases. These data
suggest that PILAB 8 can activate u-opioid receptors to provoke antinociceptive
and anti-inflammatory effects in mice.
PMID- 28509856
TI - First Report of a Fatal Case Associated with EV-D68 Infection in Hong Kong and
Emergence of an Interclade Recombinant in China Revealed by Genome Analysis.
AB - A fatal case associated with enterovirus D68 (EV-D68) infection affecting a 10
year-old boy was reported in Hong Kong in 2014. To examine if a new strain has
emerged in Hong Kong, we sequenced the partial genome of the EV-D68 strain
identified from the fatal case and the complete VP1, and partial 5'UTR and 2C
sequences of nine additional EV-D68 strains isolated from patients in Hong Kong.
Sequence analysis indicated that a cluster of strains including the previously
recognized A2 strains should belong to a separate clade, clade D, which is
further divided into subclades D1 and D2. Among the 10 EV-D68 strains, 7
(including the fatal case) belonged to the previously described, newly emerged
subclade B3, 2 belonged to subclade B1, and 1 belonged to subclade D1. Three EV
D68 strains, each from subclades B1, B3, and D1, were selected for complete
genome sequencing and recombination analysis. While no evidence of recombination
was noted among local strains, interclade recombination was identified in
subclade D2 strains detected in mainland China in 2008 with VP2 acquired from
clade A. This study supports the reclassification of subclade A2 into clade D1,
and demonstrates interclade recombination between clades A and D2 in EV-D68
strains from China.
PMID- 28509858
TI - Modes of Cell Death Induced by Photodynamic Therapy Using Zinc Phthalocyanine in
Lung Cancer Cells Grown as a Monolayer and Three-Dimensional Multicellular
Spheroids.
AB - Photodynamic therapy (PDT) involves interaction of a photosensitizer, light, and
molecular oxygen which produces singlet oxygen and subsequent tumour eradication.
The development of second generation photosensitizers, such as phthalocyanines,
has improved this technology. Customary monolayer cell culture techniques are,
unfortunately, too simple to replicate treatment effects in vivo. Multicellular
tumour spheroids may provide a better alternative since they mimic aspects of the
human tumour environment. This study aimed to profile 84 genes involved in
apoptosis following treatment with PDT on lung cancer cells (A549) grown in a
monolayer versus three-dimensional multicellular tumour spheroids (250 and 500
MUm). Gene expression profiling was performed 24 h post irradiation (680 nm; 5
J/cm2) with zinc sulfophthalocyanine (ZnPcSmix) to determine the genes involved
in apoptotic cell death. In the monolayer cells, eight pro-apoptotic genes were
upregulated, and two were downregulated. In the multicellular tumour spheroids
(250 um) there was upregulation of only 1 gene while there was downregulation of
56 genes. Apoptosis in the monolayer cultured cells was induced via both the
intrinsic and extrinsic apoptotic pathways. However, in the multicellular tumour
spheroids (250 and 500 um) the apoptotic pathway that was followed was not
conclusive.
PMID- 28509860
TI - A Combined Independent Source Separation and Quality Index Optimization Method
for Fetal ECG Extraction from Abdominal Maternal Leads.
AB - The non-invasive fetal electrocardiogram (fECG) technique has recently received
considerable interest in monitoring fetal health. The aim of our paper is to
propose a novel fECG algorithm based on the combination of the criteria of
independent source separation and of a quality index optimization (ICAQIO-based).
The algorithm was compared with two methods applying the two different criteria
independently-the ICA-based and the QIO-based methods-which were previously
developed by our group. All three methods were tested on the recently implemented
Fetal ECG Synthetic Database (FECGSYNDB). Moreover, the performance of the
algorithm was tested on real data from the PhysioNet fetal ECG Challenge 2013
Database. The proposed combined method outperformed the other two algorithms on
the FECGSYNDB (ICAQIO-based: 98.78%, QIO-based: 97.77%, ICA-based: 97.61%).
Significant differences were obtained in particular in the conditions when
uterine contractions and maternal and fetal ectopic beats occurred. On the real
data, all three methods obtained very high performances, with the QIO-based
method proving slightly better than the other two (ICAQIO-based: 99.38%, QIO
based: 99.76%, ICA-based: 99.37%). The findings from this study suggest that the
proposed method could potentially be applied as a novel algorithm for accurate
extraction of fECG, especially in critical recording conditions.
PMID- 28509861
TI - Flexible Antibacterial Coatings.
AB - This article reviews the present state of the art in the field of flexible
antibacterial coatings which efficiently kill bacteria on their surfaces.
Coatings are formed using a reactive magnetron sputtering. The effect of the
elemental composition and structure of the coating on its antibacterial and
mechanical properties is explained. The properties of Cr-Cu-O, Al-Cu-N, and Zr-Cu
N antibacterial coatings are used as examples and described in detail. The
efficiency of killing of bacteria was tested for the Escherichia coli bacterium.
The principle of the formation of thick, flexible antibacterial coatings which
are resistant to cracking under bending is explained. It is shown that magnetron
sputtering enables production of robust, several-micrometer thick, flexible
antibacterial coatings for long-term use. The antibacterial coatings produced by
magnetron sputtering present huge potential for many applications.
PMID- 28509859
TI - AlCl3.6H2O-Catalyzed Friedel-Crafts Alkylation of Indoles by the para-Quinone
Methide Moiety of Celastrol.
AB - A classical Friedel-Crafts alkylation of different indoles catalyzed by
AlCl3.6H2O has been developed for a well-known important natural product,
celastrol, resulting in a series of derivatives for further biological
evaluation. The catalyst loading was reduced to 5 mol %, the reaction proceeds at
ambient temperature and reaction time is only 3 h. The product yields range from
20% to 99%. A reaction mechanism is also proposed, based on our experiment
results.
PMID- 28509863
TI - A Fairness Oriented Neighbor-Channel-Aware MAC Protocol for Airborne Sensor
Networks.
AB - In airborne sensor networks (ASNs), the media access control (MAC) protocol faces
a serious unfairness problem due to the traditional protection mechanism of air
to-air communications among aircraft. Actually, by using the binary exponential
back-off algorithm at high traffic loads to minimize collisions among users, the
latest successful node can always benefit from this kind of MAC to obtain channel
resources. Moreover, when taking the existence of the hidden nodes in ASNs into
account, the inaccurate traffic load information will further aggravate the
system's unfairness. In this paper, a neighbor-channel-aware (NCA) protocol is
proposed to improve the fairness of MAC protocol in ASNs. In the proposal, the
NCA frame is firstly added and exchanged between neighbor nodes periodically,
which helps to resolve the inaccurate traffic load information, so as to avoid
reducing the probability of successful message transmission. Then a traffic
loading based back-off algorithm is involved to make the neighbor nodes
cooperatively adjust the inter-frame space (IFS) interval to further reduce the
unfairness. The simulation results show that, the proposed MAC protocol can
guarantee the satisfied fairness, simultaneously avoiding heavy network overloads
to protect key messages' successful transmissions in ASNs.
PMID- 28509862
TI - Cation, Anion and Ion-Pair Complexes with a G-3 Poly(ethylene imine) Dendrimer in
Aqueous Solution.
AB - The G-3 poly(ethylene imine) ligand L2 shows a multifaceted coordination ability,
being able to bind metal cations, anions and ion-pairs. The equilibrium constants
for the formation of metal (Cu2+, Zn2+), anion (SO42-) and ion-pair (Cu2+/SO42-)
complexes were determined in 0.1 M Me4NCl aqueous solution at 298.1 +/- 0.1 K by
means of potentiometric titrations. Thanks to its dendrimeric nature, L2 can form
highly nucleated metal complexes, such as Cu5L210+ and Zn4L28+, in successive and
well-defined complexation steps. Protonated forms of L2 give rise to relatively
weak anion complexes with SO42-, but the addition of Cu2+ significantly enhances
the binding ability of the ligand toward this anion below pH 9. In more alkaline
solutions, an opposite trend is observed. The coordination properties of L2 are
discussed with the support of modelling calculations. According to results, L2 is
a promising molecule for the preparation of solid supported materials for the
recovery of cations and anions from aqueous media and/or for applications in
heterogeneous catalysis.
PMID- 28509857
TI - Microbial Diversity in Extreme Marine Habitats and Their Biomolecules.
AB - Extreme marine environments have been the subject of many studies and scientific
publications. For many years, these environmental niches, which are characterized
by high or low temperatures, high-pressure, low pH, high salt concentrations and
also two or more extreme parameters in combination, have been thought to be
incompatible to any life forms. Thanks to new technologies such as metagenomics,
it is now possible to detect life in most extreme environments. Starting from the
discovery of deep sea hydrothermal vents up to the study of marine biodiversity,
new microorganisms have been identified, and their potential uses in several
applied fields have been outlined. Thermophile, halophile, alkalophile,
psychrophile, piezophile and polyextremophile microorganisms have been isolated
from these marine environments; they proliferate thanks to adaptation strategies
involving diverse cellular metabolic mechanisms. Therefore, a vast number of new
biomolecules such as enzymes, polymers and osmolytes from the inhabitant
microbial community of the sea have been studied, and there is a growing interest
in the potential returns of several industrial production processes concerning
the pharmaceutical, medical, environmental and food fields.
PMID- 28509864
TI - A Probabilistically Weakly Secure Network Coding Scheme in Multipath Routing for
WSNs.
AB - In wireless sensor networks, nodes are mostly deployed in unsupervised areas and
are vulnerable to a variety of attacks. Therefore, data security is a vital
aspect to be considered. However, due to the limited computation capability and
memory of sensor nodes, it is difficult to perform the complex encryption
algorithm, as well as the key distribution and management algorithm. Toward this
end, a low-complexity algorithm for security in wireless sensor networks is of
significant importance. In this article, a weakly secure network coding based
multipath routing scheme is proposed, which can guarantee the data
confidentiality in transmission probabilistically, and can improve the energy
efficiency in the meantime. Then the simulations of the probability of
transmission being secure are performed. The results show that with the increase
of the number of hops k, the probability of transmission being secure suffers
from a rapid decrease. On the contrary, with the increase of multicast capacity h
it undergoes a slight growth. Therefore, the weak security can be achieved with
probability approaching 1 by limiting the number of hops and increasing the
multicast capacity. Meanwhile, the simulations of energy consumption are
performed and the comparison between the energy consumption of the scheme in this
article and the multipath routing scheme without network coding is conducted. The
results show that by employing network coding, the scheme in this article can
improve the energy efficiency, and the more packets transmitted, the more energy
consumption can be reduced.
PMID- 28509865
TI - Detecting and Classifying Human Touches in a Social Robot Through Acoustic
Sensing and Machine Learning.
AB - An important aspect in Human-Robot Interaction is responding to different kinds
of touch stimuli. To date, several technologies have been explored to determine
how a touch is perceived by a social robot, usually placing a large number of
sensors throughout the robot's shell. In this work, we introduce a novel
approach, where the audio acquired from contact microphones located in the
robot's shell is processed using machine learning techniques to distinguish
between different types of touches. The system is able to determine when the
robot is touched (touch detection), and to ascertain the kind of touch performed
among a set of possibilities: stroke, tap, slap, and tickle (touch
classification). This proposal is cost-effective since just a few microphones are
able to cover the whole robot's shell since a single microphone is enough to
cover each solid part of the robot. Besides, it is easy to install and configure
as it just requires a contact surface to attach the microphone to the robot's
shell and plug it into the robot's computer. Results show the high accuracy
scores in touch gesture recognition. The testing phase revealed that Logistic
Model Trees achieved the best performance, with an F-score of 0.81. The dataset
was built with information from 25 participants performing a total of 1981 touch
gestures.
PMID- 28509867
TI - Supporting the Identification of Novel Fragment-Based Positive Allosteric
Modulators Using a Supervised Molecular Dynamics Approach: A Retrospective
Analysis Considering the Human A2A Adenosine Receptor as a Key Example.
AB - Structure-driven fragment-based (SDFB) approaches have provided efficient methods
for the identification of novel drug candidates. This strategy has been largely
applied in discovering several pharmacological ligand classes, including enzyme
inhibitors, receptor antagonists and, more recently, also allosteric (positive
and negative) modulators. Recently, Siegal and collaborators reported an
interesting study, performed on a detergent-solubilized StaR adenosine A2A
receptor, describing the existence of both fragment-like negative allosteric
modulators (NAMs), and fragment-like positive allosteric modulators (PAMs). From
this retrospective study, our results suggest that Supervised Molecular Dynamics
(SuMD) simulations can support, on a reasonable time scale, the identification of
fragment-like PAMs following their receptor recognition pathways and
characterizing the possible allosteric binding sites.
PMID- 28509868
TI - Compact Eucapnic Voluntary Hyperpnoea Apparatus for Exercise-Induced Respiratory
Disease Detection.
AB - Eucapnic voluntary hyperpnoea (EVH) challenge provides objective criteria for
exercise-induced asthma (EIA) or exercise-induced bronchoconstriction (EIB), and
it was recommended to justify the use of inhaled beta2-agonists by athletes for
the Olympics. This paper presents the development of a compact and easy-to-use
EVH apparatus for assessing EIB in human subjects. The compact apparatus has been
validated on human subjects and the results have been compared to the
conventional EVH system. Twenty-two swimmers, including eleven healthy subjects
and eleven subjects who had been physician-diagnosed with asthma, were recruited
from sport and recreation centers throughout Auckland, New Zealand. Each subject
performed two EVH challenge tests using the proposed breathing apparatus and the
conventional Phillips EVH apparatus on separate days, respectively. Forced
expiratory volume in one second (FEV1) was measured before and after the
challenges. A reduction in FEV1 of 10% or more was considered positive. Of the
eleven subjects who were previously diagnosed with asthma, EIB was present in all
subjects (100%) in the compact EVH group, while it was presented in ten subjects
(90.91%) in the conventional EVH challenge group. Of the eleven healthy subjects,
EIB was present in one subject (4.55%) in the compact EVH group, while it was not
present in the conventional EVH group. Experimental results showed that the
compact EVH system has potential to become an alternative tool for EIB detection.
PMID- 28509869
TI - Experimental Approach for the Uncertainty Assessment of 3D Complex Geometry
Dimensional Measurements Using Computed Tomography at the mm and Sub-mm Scales.
AB - The dimensional verification of miniaturized components with 3D complex
geometries is particularly challenging. Computed Tomography (CT) can represent a
suitable alternative solution to micro metrology tools based on optical and
tactile techniques. However, the establishment of CT systems' traceability when
measuring 3D complex geometries is still an open issue. In this work, an
alternative method for the measurement uncertainty assessment of 3D complex
geometries by using CT is presented. The method is based on the micro-CT system
Maximum Permissible Error (MPE) estimation, determined experimentally by using
several calibrated reference artefacts. The main advantage of the presented
method is that a previous calibration of the component by a more accurate
Coordinate Measuring System (CMS) is not needed. In fact, such CMS would still
hold all the typical limitations of optical and tactile techniques, particularly
when measuring miniaturized components with complex 3D geometries and their
inability to measure inner parts. To validate the presented method, the most
accepted standard currently available for CT sensors, the Verein Deutscher
Ingenieure/Verband Deutscher Elektrotechniker (VDI/VDE) guideline 2630-2.1 is
applied. Considering the high number of influence factors in CT and their impact
on the measuring result, two different techniques for surface extraction are also
considered to obtain a realistic determination of the influence of data
processing on uncertainty. The uncertainty assessment of a workpiece used for
micro mechanical material testing is firstly used to confirm the method, due to
its feasible calibration by an optical CMS. Secondly, the measurement of a
miniaturized dental file with 3D complex geometry is carried out. The estimated
uncertainties are eventually compared with the component's calibration and the
micro manufacturing tolerances to demonstrate the suitability of the presented CT
calibration procedure. The 2U/T ratios resulting from the validation workpiece
are, respectively, 0.27 (VDI) and 0.35 (MPE), by assuring tolerances in the range
of +/- 20-30 um. For the dental file, the EN < 1 value analysis is favorable in
the majority of the cases (70.4%) and 2U/T is equal to 0.31 for sub-mm measurands
(L < 1 mm and tolerance intervals of +/- 40-80 um).
PMID- 28509866
TI - HDAC8 Prevents Anthrax Lethal Toxin-induced Cell Cycle Arrest through Silencing
PTEN in Human Monocytic THP-1 Cells.
AB - Anthrax lethal toxin (LeTx) is a cytotoxic virulence factor that causes cell
cycle arrest and cell death in various cell types. However, susceptibility to the
cytotoxic effects varies depending on cell types. In proliferating monocytes,
LeTx has only transient cytotoxic effects due to activation of the
phosphoinositide 3-kinase (PI3K)-AKT-mediated adaptive responses. To date, the
mechanism of LeTx in activating PI3K-AKT signaling axis is unknown. This study
shows that the histone deacetylase 8 (HDAC8) is involved in activating PI3K-AKT
signaling axis through down-regulating the phosphatase and tensin homolog 1
(PTEN) in human monocytic THP-1 cells. The HDAC8-specific activator TM-2-51 and
inhibitor PCI-34051 enhanced and prevented, respectively, AKT activation and cell
cycle progression in LeTx-treated cells. Furthermore, HDAC8 induced tri
methylation of histone H3 lysine 27 (H3K27me3), which is known to suppress PTEN
expression, through at least in part down-regulating the H3K27me3 eraser Jumonji
Domain Containing (JMJD) 3. Importantly, the JMJD3-specific inhibitor GSK-J4
induced AKT activation and protected cell cycle arrest in LeTx-treated cells,
regardless the presence of HDAC8 activity. Collectively, this study for the first
time demonstrated that HDAC8 activity determines susceptibility to cell cycle
arrest induced by LeTx, through regulating the PI3K-PTEN-AKT signaling axis.
PMID- 28509870
TI - Sound Power Estimation for Beam and Plate Structures Using Polyvinylidene
Fluoride Films as Sensors.
AB - The theory for calculation and/or measurement of sound power based on the
classical velocity-based radiation mode (V-mode) approach is well established for
planar structures. However, the current V-mode theory is limited in scope in that
it can only be applied to conventional motion sensors (i.e., accelerometers). In
this study, in order to estimate the sound power of vibrating beam and plate
structure by using polyvinylidene fluoride (PVDF) films as sensors, a PVDF-based
radiation mode (C-mode) approach concept is introduced to determine the sound
power radiation from the output signals of PVDF films of the vibrating structure.
The proposed method is a hybrid of vibration measurement and numerical
calculation of C-modes. The proposed C-mode approach has the following
advantages: (1) compared to conventional motion sensors, the PVDF films are
lightweight, flexible, and low-cost; (2) there is no need for special measuring
environments, since the proposed method does not require the measurement of sound
fields; (3) In low frequency range (typically with dimensionless frequency kl <
4), the radiation efficiencies of the C-modes fall off very rapidly with
increasing mode order, furthermore, the shapes of the C-modes remain almost
unchanged, which means that the computation load can be significantly reduced due
to the fact only the first few dominant C-modes are involved in the low frequency
range. Numerical simulations and experimental investigations were carried out to
verify the accuracy and efficiency of the proposed method.
PMID- 28509871
TI - Nutraceutical Value of Citrus Flavanones and Their Implications in Cardiovascular
Disease.
AB - Background- Cardiovascular diseases, including myocardial infarction,
dyslipidaemia and coronary artery pathology, are a major cause of illness and
death in Western countries. Therefore, identifying effective therapeutic
approaches and their cellular signalling pathways is a challenging goal for
medicine. In this regard, several epidemiological studies demonstrate a
relationship between the intake of flavonoid-rich foods and the reduction of
cardiovascular risk factors and mortality. In particular, flavonoids present in
citrus fruits, such as oranges, bergamots, lemons and grapefruit (95% from
flavanones), are emerging for their considerable nutraceutical value. Methods- In
this review an examination of literature was performed while considering both
epidemiological, clinical and pre-clinical evidence supporting the beneficial
role of the flavanone class. We evaluated studies in which citrus fruit juices or
single flavanone administration and cardiovascular risk factors were analysed; to
identify these studies, an electronic search was conducted in PUBMED for papers
fulfilling these criteria and written in English. Results- In addition to
epidemiological evidence and clinical studies demonstrating that fruits in the
Citrus genus significantly reduce the incidence of cardiovascular disease risk,
pre-clinical investigations highlight cellular and subcellular targets that are
responsible for these beneficial effects. There has been special attention on
evaluating intracellular pathways involved in direct cardiovascular and
cardiometabolic effects mediated by naringenin, hesperetin and eriodictyol or
their glycosylated derivatives. Conclusions- Although some mechanisms of action
remain unclear and bioavailability problems remain to be solved, the current
evidence supports the use of a nutraceutical approach with citrus fruits to
prevent and cure several aspects of cardiovascular disease.
PMID- 28509872
TI - Synthesis of Pyrimethanil-Loaded Mesoporous Silica Nanoparticles and Its
Distribution and Dissipation in Cucumber Plants.
AB - Mesoporous silica nanoparticles are used as pesticide carries in plants, which
has been considered as a novel method to reduce the indiscriminate use of
conventional pesticides. In the present work, mesoporous silica nanoparticles
with particle diameters of 200-300 nm were synthesized in order to obtain
pyrimethanil-loaded nanoparticles. The microstructure of the nanoparticles was
observed by scanning electron microscopy. The loading content of pyrimethanil
loaded nanoparticles was investigated. After treatment on cucumber leaves, the
concentrations of pyrimethanil were determined in different parts of cucumber
over a period of 48 days using high performance liquid chromatography tandem mass
spectrometry. It was shown that the pyrimethanil-loaded mesoporous silica
nanoparticles might be more conducive to acropetal, rather than basipetal,
uptake, and the dosage had almost no effect on the distribution and dissipation
rate in cucumber plants. The application of the pesticide-loaded nanoparticles in
leaves had a low risk of pyrimethanil accumulating in the edible part of the
plant.
PMID- 28509873
TI - Leishmanicidal Activity and Structure-Activity Relationships of Essential Oil
Constituents.
AB - Several constituents of essential oils have been shown to be active against
pathogens such as bacteria, fungi, and protozoa. This study demonstrated the in
vitro action of ten compounds present in essential oils against Leishmania
amazonensis promastigotes. With the exception of p-cymene, all evaluated
compounds presented leishmanicidal activity, exhibiting IC50 between 25.4 and
568.1 MUg mL-1. Compounds with the best leishmanicidal activity presented a
phenolic moiety (IC50 between 25.4 and 82.9 MUg mL-1). Alicyclic alcohols ((-)
menthol and isoborneol) and ketones ((-)-carvone) promoted similar activity
against the parasite (IC50 between 190.2 and 198.9 MUg mL-1). Most of the
compounds showed low cytotoxicity in L929 fibroblasts. Analysis of the structure
activity relationship of these compounds showed the importance of the phenolic
structure for the biological action against the promastigote forms of the
parasite.
PMID- 28509874
TI - Evaluation of the Mycobactericidal Effect of Thio-functionalized Carbohydrate
Derivatives.
AB - Sugars with heteroatoms other than oxygen have attained considerable importance
in glycobiology and in drug design since they are often more stable in blood
plasma due to their resistance to enzymes, such as glycosidases, phosphorylases
and glycosyltransferases. The replacement of oxygen atoms in sugars with sulfur
forms thio-sugars, which are potentially useful for the treatment of diabetes and
some bacterial and viral infections. Here, we evaluated the antibacterial
activity of thio-functionalized carbohydrate derivatives. A set of 21 compounds
was screened against acid-fast Mycobacterium tuberculosis (Mtb), gram-negative
Escherichia coli and gram-positive Staphylococcus aureus. The tested carbohydrate
derivatives were most effective against tubercle bacilli, with as many as five
compounds (thioglycoside 6, thiosemicarbazone 16A, thiosemicarbazone 20,
aminothiadiazole 23, and thiazoline 26) inhibiting its growth with MIC50 <= 50
uM/CFU. Only two compounds (aminothiadiazole 23 and thiazoline 26) were able to
inhibit the growth of E. coli at concentrations below 1 mM, and one of them,
aminothiadiazole 23, inhibited the growth of S. aureus at a concentration <=1 mM.
The five compounds affecting the growth of mycobacteria were either
thiodisaccharides (6, 16A, and 20) or thioglycosides (23 and 26). All of these
compounds (6, 16A, 20, 23, and 26) were able to inhibit the growth of Mtb
deposited within human macrophages. However, three of the five selected compounds
(6, 23, and 26) exhibited relatively high cytotoxicity in mouse fibroblasts at
micromolar concentrations. The selected thio-sugars are very promising compounds,
thus making them candidates for further modifications that would decrease their
cytotoxicity against eukaryotic cells without affecting their antimycobacterial
potential.
PMID- 28509875
TI - In Silico Analysis of Epitope-Based Vaccine Candidates against Hepatitis B Virus
Polymerase Protein.
AB - Hepatitis B virus (HBV) infection has persisted as a major public health problem
due to the lack of an effective treatment for those chronically infected.
Therapeutic vaccination holds promise, and targeting HBV polymerase is pivotal
for viral eradication. In this research, a computational approach was employed to
predict suitable HBV polymerase targeting multi-peptides for vaccine candidate
selection. We then performed in-depth computational analysis to evaluate the
predicted epitopes' immunogenicity, conservation, population coverage, and
toxicity. Lastly, molecular docking and MHC-peptide complex stabilization assay
were utilized to determine the binding energy and affinity of epitopes to the HLA
A0201 molecule. Criteria-based analysis provided four predicted epitopes,
RVTGGVFLV, VSIPWTHKV, YMDDVVLGA and HLYSHPIIL. Assay results indicated the lowest
binding energy and high affinity to the HLA-A0201 molecule for epitopes VSIPWTHKV
and YMDDVVLGA and epitopes RVTGGVFLV and VSIPWTHKV, respectively. Regions 307 to
320 and 377 to 387 were considered to have the highest probability to be involved
in B cell epitopes. The T cell and B cell epitopes identified in this study are
promising targets for an epitope-focused, peptide-based HBV vaccine, and provide
insight into HBV-induced immune response.
PMID- 28509876
TI - Optimization of EPS Production and Characterization by a Halophilic Bacterium,
Kocuria rosea ZJUQH from Chaka Salt Lake with Response Surface Methodology.
AB - With the rising awareness of microbial exopolysaccharides (EPSs) application in
various fields, halophilic microorganisms which produce EPSs have received broad
attention. A newly identified Kocuria rosea ZJUQH CCTCC M2016754 was determined
to be a moderate halobacterium on account of its successful adaption to the
environment containing 10% NaCl. The optimal combination of fermentation medium
compositions on EPS production was studied. In this work, a fractional factorial
design was adopted to investigate the significant factors that affected EPS
production. The factors of KCl and MgSO4 were found to have a profound impact on
EPS production. We utilized central composite design and response surface
methodology to derive a statistical model for optimizing the submerged culture
medium composition. Judging from these experimental results, the optimum culture
medium for producing EPSs was composed of 0.50% casein hydrolysate, 1.00% sodium
citrate, 0.30% yeast extract, 0.50% KCl, 0.50% peptone, and 5.80% MgSO4 (initial
pH 7.0). The maximal EPS was 48.01 g/L, which is close to the predicted value
(50.39 g/L). In the validation experiment, the highest concentration of 70.64 g/L
EPSs was obtained after 120 h under the optimized culture medium in a 5-L
bioreactor. EPS from this bacterium was also characterized by differential
scanning calorimetry (DSC) and Fourier transform infrared analysis (FT-IR). The
findings in this study imply that Kocuria rosea ZJUQH has great potential to be
exploited as a source of EPSs utilized in food, the pharmaceutical and
agriculture industry, and in the biotreatment of hypersaline environments.
PMID- 28509877
TI - Human Beta Defensin 2 Selectively Inhibits HIV-1 in Highly Permissive CCR6+CD4+ T
Cells.
AB - Chemokine receptor type 6 (CCR6)+CD4+ T cells are preferentially infected and
depleted during HIV disease progression, but are preserved in non-progressors.
CCR6 is expressed on a heterogeneous population of memory CD4+ T cells that are
critical to mucosal immunity. Preferential infection of these cells is
associated, in part, with high surface expression of CCR5, CXCR4, and
alpha4beta7. In addition, CCR6+CD4+ T cells harbor elevated levels of integrated
viral DNA and high levels of proliferation markers. We have previously shown that
the CCR6 ligands MIP-3alpha and human beta defensins inhibit HIV replication. The
inhibition required CCR6 and the induction of APOBEC3G. Here, we further
characterize the induction of apolipoprotein B mRNA editing enzyme (APOBEC3G) by
human beta defensin 2. Human beta defensin 2 rapidly induces transcriptional
induction of APOBEC3G that involves extracellular signal-regulated kinases 1/2
(ERK1/2) activation and the transcription factors NFATc2, NFATc1, and IRF4. We
demonstrate that human beta defensin 2 selectively protects primary CCR6+CD4+ T
cells infected with HIV-1. The selective protection of CCR6+CD4+ T cell subsets
may be critical in maintaining mucosal immune function and preventing disease
progression.
PMID- 28509879
TI - Quality over Quantity: Contribution of Urban Green Space to Neighborhood
Satisfaction.
AB - There is increasing evidence that the quality of green space significantly
contributes to neighborhood satisfaction and well-being, independent of the mere
amount of green space. In this paper, we examined residents' perceptions of the
quality and beneficial affordances of green space in relation to objectively
assessed accessibility and usability. We used data from a survey in two
neighborhoods (N = 223) of a medium-sized city in the Netherlands, which were
similar in the amount of green space and other physical and socio-demographic
characteristics, but differed in the availability of accessible and usable green
spaces. Results show that residents of the neighborhood with a higher
availability of accessible and usable green spaces were more satisfied with their
neighborhood. This difference was statistically mediated by the higher level of
perceived green space quality. Neighborhood satisfaction was significantly
positively related to well-being. However, residents of the two neighborhoods did
not differ in self-reported well-being and beneficial affordances of green space.
These analyses contribute to a further understanding of how the accessibility and
usability of green spaces may increase people's neighborhood satisfaction. It
highlights the importance of perceived quality in addition to the amount of green
space when examining the beneficial effects of green space.
PMID- 28509880
TI - Analysis of Different Approaches for the Selection of Reference Genes in RT-qPCR
Experiments: A Case Study in Skeletal Muscle of Growing Mice.
AB - The reliability of reverse transcription-quantitative PCR (RT-qPCR) results in
gene expression studies depends on the approaches used to account for non
biological variations. In order to find a proper normalization strategy for the
study of genes related to growth hormone signaling in skeletal muscle of growing
mice, nine unrelated genes were evaluated as internal controls. According to the
most used algorithms-geNorm, the Comparative DeltaCq method, NormFinder and
BestKeeper-GSK3B, YWHAZ, RPL13A and RN18S were found as the most stable. However,
the relative expression levels of eight of the potential reference genes assessed
decreased with age in cDNA samples obtained from the same amount of total RNA. In
a different approach to analyze this apparent discrepancy, experiments were
performed with cDNA obtained from equal amounts of purified mRNA. Since the
decline was still observed, the hypothesis of an age-related change in mRNA to
total RNA ratio that could account for the systematic decrease was rejected.
Differences among experimental groups could be due to a substantial increase with
age in highly expressed mRNAs, which would bias the quantitation of the remaining
genes. Consequently, those reference genes reflecting this dilution effect, which
would have been discarded considering their variable relative expression levels,
arose as suitable internal controls.
PMID- 28509878
TI - Antigenic and Biological Characterization of ORF2-6 Variants at Early Times
Following PRRSV Infection.
AB - Genetic diversity of porcine reproductive and respiratory syndrome virus (PRRSV)
challenges efforts to develop effective and broadly acting vaccines. Although
genetic variation in PRRSV has been extensively documented, the effects of this
variation on virus phenotype are less well understood. In the present study,
PRRSV open reading frame (ORF)2-6 variants predominant during the first six weeks
following experimental infection were characterized for antigenic and replication
phenotype. There was limited genetic variation during these early times after
infection; however, distinct ORF2-6 haplotypes that differed from the NVSL97-7895
inoculum were identified in each of the five pigs examined. Chimeric viruses
containing all or part of predominant ORF2-6 haplotypes were constructed and
tested in virus neutralization and in vitro replication assays. In two pigs,
genetic variation in ORF2-6 resulted in increased resistance to neutralization by
autologous sera. Mapping studies indicated that variation in either ORF2-4 or
ORF5-6 could confer increased neutralization resistance, but there was no single
amino acid substitution that was predictive of neutralization phenotype. Detailed
analyses of the early steps in PRRSV replication in the presence and absence of
neutralizing antibody revealed both significant inhibition of virion attachment
and, independently, a significant delay in the appearance of newly synthesized
viral RNA. In all pigs, genetic variation in ORF2-6 also resulted in significant
reduction in infectivity on MARC-145 cells, suggesting variation in ORF2-6 may
also be important for virus replication in vivo. Together, these data reveal that
variation appearing early after infection, though limited, alters important virus
phenotypes and contributes to antigenic and biologic diversity of PRRSV.
PMID- 28509883
TI - Deposition of Visible Light-Active C-Doped Titania Films via Magnetron Sputtering
Using CO2 as a Source of Carbon.
AB - Doping of titanium dioxide with p-block elements is typically described as an
efficient pathway for the enhancement of photocatalytic activity. However, the
properties of the doped titania films depend greatly on the production method,
source of doping, type of substrate, etc. The present work describes the use of
pulsed direct current (pDC) magnetron sputtering for the deposition of carbon
doped titania coatings, using CO2 as the source of carbon; ratios of O2/CO2 were
varied through variations of CO2 flow rates and oxygen flow control setpoints.
Additionally, undoped Titanium dioxide (TiO2) coatings were prepared under
identical deposition conditions for comparison purposes. Coatings were post
deposition annealed at 873 K and analysed with scanning electron microscopy
(SEM), X-ray diffreaction (XRD), atomic force microscopy (AFM), and X-ray
photoelectron spectroscopy (XPS). The photocatalytic properties of the thin films
were evaluated under ultraviolet (UV) and visible light irradiation using
methylene blue and stearic acid decomposition tests. Photoinduced hydrophilicity
was assessed through measurements of the water contact angle under UV and visible
light irradiation. It was found that, though C-doping resulted in improved dye
degradation compared to undoped TiO2, the UV-induced photoactivity of Carbon
doped (C-doped) photocatalysts was lower for both model pollutants used.
PMID- 28509882
TI - Emerging Evidence on Neutrophil Motility Supporting Its Usefulness to Define
Vitamin C Intake Requirements.
AB - Establishing intake recommendations for vitamin C remains a challenge, as no
suitable functional parameter has yet been agreed upon. In this report, we review
the emerging evidence on neutrophil motility as a possible marker of vitamin C
requirements and put the results in perspective with other approaches. A recent
in vitro study showed that adequate levels of vitamin C were needed for this
function to work optimally when measured as chemotaxis and chemokinesis. In a
human study, neutrophil motility was optimal at intakes >=250 mg/day.
Interestingly, a Cochrane review showed a significant reduction in the duration
of episodes of common cold with regular vitamin C intakes in a similar range.
Additionally, it was shown that at a plasma level of 75 umol/L, which is reached
with vitamin C intakes >=200 mg/day, incidences of cardiovascular disease were
lowest. This evidence would suggest that daily intakes of 200 mg vitamin C might
be advisable for the general adult population, which can be achieved by means of
a diverse diet. However, additional studies are warranted to investigate the
usefulness of neutrophil motility as a marker of vitamin C requirements.
PMID- 28509884
TI - One-Flask Synthesis of Pyrazolo[3,4-d]pyrimidines from 5-Aminopyrazoles and
Mechanistic Study.
AB - A novel one-flask synthetic method was developed in which 5-aminopyrazoles were
reacted with N,N-substituted amides in the presence of PBr3. Hexamethyldisilazane
was then added to perform heterocyclization to produce the corresponding
pyrazolo[3,4-d]pyrimidines in suitable yields. These one-flask reactions thus
involved Vilsmeier amidination, imination reactions, and the sequential
intermolecular heterocyclization. To study the reaction mechanism, a series of 4
formyl-1,3-diphenyl-1H-pyrazol-5-yl-N,N-disubstituted formamidines, which were
conceived as the chemical equivalent of 4-(iminomethyl)-1,3-diphenyl-1H-pyrazol-5
yl-formamidine, were prepared and successfully converted into pyrazolo[3,4
d]pyrimidines. The experiments demonstrated that the reaction intermediates were
the chemical equivalents of 4-(iminomethyl)-1,3-diphenyl-1H-pyrazol-5
yl)formamidines. The rate of the reaction could be described as being
proportional to the reactivity of amine reactants during intermolecular
heterocyclization, especially when hexamethyldisilazane was used.
PMID- 28509881
TI - dFmr1 Plays Roles in Small RNA Pathways of Drosophila melanogaster.
AB - Fragile-X syndrome is the most common form of inherited mental retardation
accompanied by other phenotypes, including macroorchidism. The disorder
originates with mutations in the Fmr1 gene coding for the FMRP protein, which,
with its paralogs FXR1 and FXR2, constitute a well-conserved family of RNA
binding proteins. Drosophila melanogaster is a good model for the syndrome
because it has a unique fragile X-related gene: dFmr1. Recently, in addition to
its confirmed role in the miRNA pathway, a function for dFmr1 in the piRNA
pathway, operating in Drosophila gonads, has been established. In this review we
report a summary of the piRNA pathways occurring in gonads with a special
emphasis on the relationship between the piRNA genes and the crystal-Stellate
system; we also analyze the roles of dFmr1 in the Drosophila gonads, exploring
their genetic and biochemical interactions to reveal some unexpected connections.
PMID- 28509885
TI - The Role of Phytochemicals in the Inflammatory Phase of Wound Healing.
AB - Historically, plant-based products have been the basis of medicine since before
the advent of modern Western medicine. Wound dressings made of honey, curcumin
and other phytochemical-rich compounds have been traditionally used. Recently,
the mechanisms behind many of these traditional therapies have come to light. In
this review, we show that in the context of wound healing, there is a global
theme of anti-inflammatory and antioxidant phytochemicals in traditional
medicine. Although promising, we discuss the limitations of using some of these
phytochemicals in order to warrant more research, ideally in randomized clinical
trial settings.
PMID- 28509886
TI - An Improved DOA Estimation Approach Using Coarray Interpolation and Matrix
Denoising.
AB - Co-prime arrays can estimate the directions of arrival (DOAs) of O ( M N )
sources with O ( M + N ) sensors, and are convenient to analyze due to their
closed-form expression for the locations of virtual lags. However, the number of
degrees of freedom is limited due to the existence of holes in difference
coarrays if subspace-based algorithms such as the spatial smoothing multiple
signal classification (MUSIC) algorithm are utilized. To address this issue,
techniques such as positive definite Toeplitz completion and array interpolation
have been proposed in the literature. Another factor that compromises the
accuracy of DOA estimation is the limitation of the number of snapshots. Coarray
based processing is particularly sensitive to the discrepancy between the sample
covariance matrix and the ideal covariance matrix due to the finite number of
snapshots. In this paper, coarray interpolation based on matrix completion (MC)
followed by a denoising operation is proposed to detect more sources with a
higher accuracy. The effectiveness of the proposed method is based on the
capability of MC to fill in holes in the virtual sensors and that of MC denoising
operation to reduce the perturbation in the sample covariance matrix. The results
of numerical simulations verify the superiority of the proposed approach.
PMID- 28509888
TI - Cardiac Contractility Modulation: A Technical Guide for Device Implantation.
AB - This article provides a technical description of common implant practice for
delivery of cardiac contractility modulation (CCM) therapy to heart failure
patients. As of September 2016, the authors of this article collectively have
been involved with more than 400 system implantations in five medical centers,
beginning with the advent of CCM therapy approximately 12 years ago. CCM therapy
has been evaluated in a variety of studies, and was shown to be safe and
effective and of benefit to patient quality of life and exercise capacity. As the
use of CCM therapy continuously expands among medical centers in Europe, this
article describes the technical and practical aspects of the implant procedure,
and additional special technical cases based on our cumulative experience.
PMID- 28509889
TI - The Role of Nitrates in the Management of Stable Ischemic Heart Disease: A Review
of the Current Evidence and Guidelines.
AB - Coronary artery disease is the leading cause of mortality in the United States
and can result in significant morbidity. In particular, stable ischemic heart
disease (SIHD) is a condition that affects nearly 9 million individuals in the
United States alone, with substantial annual health care costs related to
recurrent medical visits and chronic disease management. Nitrates form a
cornerstone of SIHD management by reducing myocardial oxygen consumption and
increasing exercise capacity by several mechanisms, including increasing
epicardial blood flow through vasodilation and decreased vascular resistance,
blunting coronary steal, and reducing preload. Yet the role of nitrates may be
underappreciated in clinical practice and their utilization may be limited due to
concerns of tolerance to treatment, a lack of randomized data validating their
ability to prevent adverse cardiovascular events, and the pervasive use of
percutaneous interventions without robust attempts at implementing optimal
medical therapy. In this review, we discuss both the recent
ACC/AHA/ACP/AATS/PCNA/SCAI/STS and European Society of Cardiology guidelines,
with a particular focus on indications, contraindications, and future directions
of nitrate therapy in SIHD.
PMID- 28509890
TI - Balancing Low-density Lipoprotein Cholesterol Reduction and Hepatotoxicity With
Lomitapide Mesylate and Mipomersen in Patients With Homozygous Familial
Hypercholesterolemia.
AB - Homozygous familial hypercholesterolemia (HoFH) is an autosomal codominant
disorder manifested by high concentrations of total cholesterol and low-density
lipoprotein (LDL) cholesterol, and premature cardiovascular disease. Despite
conventional lipid-lowering therapy, LDL cholesterol levels remain elevated in
patients with HoFH; these patients are considered to be at high risk for
cardiovascular events. In 2012-2013, two drugs with novel mechanisms of action
were approved by the US Food and Drug Administration for the treatment of HoFH:
lomitapide mesylate and mipomersen. Both of these treatments reduce total
cholesterol, LDL cholesterol, non-high-density lipoprotein cholesterol,
apolipoprotein B, lipoprotein a, and triglyceride levels. This review describes
the clinical tradeoffs in efficacy and hepatotoxicity of these drugs in two cases
of HoFH.
PMID- 28509887
TI - Predictors of Segmented School Day Physical Activity and Sedentary Time in
Children from a Northwest England Low-Income Community.
AB - BACKGROUND: Schools have been identified as important settings for health
promotion through physical activity participation, particularly as children are
insufficiently active for health. The aim of this study was to investigate the
child and school-level influences on children's physical activity levels and
sedentary time during school hours in a sample of children from a low-income
community; Methods: One hundred and eighty-six children (110 boys) aged 9-10
years wore accelerometers for 7 days, with 169 meeting the inclusion criteria of
16 h?day-1 for a minimum of three week days. Multilevel prediction models were
constructed to identify significant predictors of sedentary time, light, and
moderate to vigorous physical activity during school hour segments. Child-level
predictors (sex, weight status, maturity offset, cardiorespiratory fitness,
physical activity self-efficacy, physical activity enjoyment) and school-level
predictors (number on roll, playground area, provision score) were entered into
the models; Results: Maturity offset, fitness, weight status, waist circumference
to-height ratio, sedentary time, moderate to vigorous physical activity, number
of children on roll and playground area significantly predicted physical activity
and sedentary time; Conclusions: Research should move towards considering context
specific physical activity and its correlates to better inform intervention
strategies.
PMID- 28509891
TI - Spontaneous Coronary Artery Dissection: A Review of Pathogenesis, Presentations,
Treatment, and Outcomes.
AB - Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary
syndromes and sudden cardiac death. The epidemiology, pathogenesis, and optimal
approaches to diagnosis and management are poorly understood. Additionally, SCAD
as a syndrome is commonly under-recognized and its prognosis is not well studied.
Guidelines on management of SCAD have not yet been established. We present three
cases of SCAD that varied in their clinical presentation and describe the
different management strategies utilized. This is followed by a review of the
clinical features, epidemiology, prognosis, and potential treatment strategies
for patients presenting with SCAD.
PMID- 28509892
TI - Arrhythmogenic Right Ventricular Dysplasia: An Under-recognized Form of Inherited
Cardiomyopathy.
AB - We report a case of arrhythmogenic right ventricular cardiomyopathy/dysplasia
(ARVD) in order to evaluate the course of an under-recognized form of
cardiomyopathy with a vast array of clinical manifestations. The patient is a 49
year-old white woman transferred from an outside hospital due to dyspnea and
persistent hypoxia. She had a pertinent family history that included a sister who
died suddenly in her 30s from unexplained heart failure. Initial work-up for
hypoxia was unrevealing. Transthoracic echocardiography revealed isolated right
ventricular dysfunction with dilation and multiple trabeculations. Further
investigation, including cardiac computed tomography and magnetic resonance
imaging, revealed fatty infiltration into the right ventricular wall suggestive
of ARVD.
PMID- 28509893
TI - Spontaneous Coronary Artery Dissection: Insights From Histology and Optical
Coherence Tomography.
AB - Spontaneous coronary artery dissection (SCAD) is a well-known but infrequent
cause of acute coronary syndrome (ACS), and often goes unrecognized. Although
management of SCAD is, at times, controversial, when a patient presents with ACS,
percutaneous coronary intervention (PCI) is frequently necessary. We present a
patient with ST-segment elevation myocardial infarction (STEMI) with SCAD that
illustrates two important points: use of intracoronary optical coherence
tomography to guide PCI, and histologic assessment to provide a unique insight
into the etiology of SCAD. Following the case, we briefly review the important
aspects of the pathophysiology, epidemiology, diagnosis, and interventional
management of SCAD.
PMID- 28509894
TI - Swallowing-induced Supraventricular Tachyarrhythmia.
AB - Swallowing-induced supraventricular tachyarrhythmia is an extremely rare entity
with unclear pathophysiology. A 55-year-old man presented with a 2-year history
of worsening presyncopal symptoms triggered only by drinking liquids of any
temperature. Results of a physical examination were unremarkable except for
reproducible atrial tachycardias to 180 to 210 beats/minute documented on rhythm
strips when the patient was given water to drink. He underwent radiofrequency
ablation with complete resolution of symptoms. We reviewed all 43 published cases
of swallowing-induced supraventricular tachyarrhythmia in the English-language
medical literature. We found only one other reported case induced only by
drinking liquids. Radiofrequency ablation appears to be the treatment of choice.
PMID- 28509896
TI - Inferring personal economic status from social network location.
AB - It is commonly believed that patterns of social ties affect individuals' economic
status. Here we translate this concept into an operational definition at the
network level, which allows us to infer the economic well-being of individuals
through a measure of their location and influence in the social network. We
analyse two large-scale sources: telecommunications and financial data of a whole
country's population. Our results show that an individual's location, measured as
the optimal collective influence to the structural integrity of the social
network, is highly correlated with personal economic status. The observed social
network patterns of influence mimic the patterns of economic inequality. For
pragmatic use and validation, we carry out a marketing campaign that shows a
threefold increase in response rate by targeting individuals identified by our
social network metrics as compared to random targeting. Our strategy can also be
useful in maximizing the effects of large-scale economic stimulus policies.
PMID- 28509895
TI - [Chronic Malnutrition among Children under Five in Peru: A Spatial Analysis of
Nutritional Data, 2010-2016].
AB - OBJECTIVE: Peru has implemented various strategies seeking to improve nutritional
indicators in children under five years old. However, high prevalence of
malnutrition in some regions still remains. The aim of this study was to assess
changes in regional prevalence and to determine the presence of district
conglomerates with a high prevalence of chronic childhood malnutrition (CCM) in
2010 and 2016. METHODS: A comparative descriptive analysis by regions and a
district-level spatial analysis were conducted employing indicators reported by
the Nutritional Status Information System. RESULTS: 23.9% (561.090/2.343.806)
children under five years evaluated in Peru during 2010 and 18.0%
(394.049/2.193.268) evaluated during 2016 were chronic malnutrition (reduction of
5.9 percentage points). We identified a decline of 7.6 percent points in rural
areas and the persistence of prevalence above 30% in only one region
(Huancavelica). The spatial analysis identified clusters of districts with high
prevalence in 20% (379/1834) of Peruvian districts in 2010, and 17.2% (316/1834)
of those in 2016, which are mainly spread across the sierra and jungle regions..
CONCLUSIONS: Peru has made significant progress in reducing stunting in children.
Nevertheless, it still represents a health problem due to high prevalence in the
sierra region, as well as expansion to jungle districts in 2016.
PMID- 28509897
TI - Disambiguation of patent inventors and assignees using high-resolution
geolocation data.
AB - Patent data represent a significant source of information on innovation,
knowledge production, and the evolution of technology through networks of
citations, co-invention and co-assignment. A major obstacle to extracting useful
information from this data is the problem of name disambiguation: linking
alternate spellings of individuals or institutions to a single identifier to
uniquely determine the parties involved in knowledge production and diffusion. In
this paper, we describe a new algorithm that uses high-resolution geolocation to
disambiguate both inventors and assignees on about 8.5 million patents found in
the European Patent Office (EPO), under the Patent Cooperation Treaty (PCT), and
in the US Patent and Trademark Office (USPTO). We show this disambiguation is
consistent with a number of ground-truth benchmarks of both assignees and
inventors, significantly outperforming the use of undisambiguated names to
identify unique entities. A significant benefit of this work is the high quality
assignee disambiguation with coverage across the world coupled with an inventor
disambiguation (that is competitive with other state of the art approaches) in
multiple patent offices.
PMID- 28509898
TI - Modern pollen data from the Canadian Arctic, 1972-1973.
AB - This data descriptor reports results of a 1972-73 baseline study of modern pollen
deposition in the Canadian Arctic to originally aid interpretation of Holocene
pollen diagrams from that region, especially focussed on the arctic tree-line.
The data set is geographically unique due to its extent, and allows the
assessment of the effects of modern climate change on northern ecosystems,
including fluctuations of the a arctic tree-line. Repeated sampling was conducted
along an interior transect at 29 sites from the Boreal Forest to the High Arctic,
with five additional coastal sites covering a total distance of 3,200 km. Static
pollen samplers captured both local pollen and long-distance pollen wind-blown
from the Boreal Forest. Moss and lichen polsters provided multi-year pollen
fallout to assess the effectiveness of the static pollen samplers. The local
vegetation was recorded at each site. This descriptor provides information on
data archived at the World Data Center PANGAEA, which includes spreadsheets
detailing site and sample information as well as raw and processed pollen data
obtained on over 500 samples.
PMID- 28509899
TI - A bioprosthetic ovary created using 3D printed microporous scaffolds restores
ovarian function in sterilized mice.
AB - Emerging additive manufacturing techniques enable investigation of the effects of
pore geometry on cell behavior and function. Here, we 3D print microporous
hydrogel scaffolds to test how varying pore geometry, accomplished by
manipulating the advancing angle between printed layers, affects the survival of
ovarian follicles. 30 degrees and 60 degrees scaffolds provide corners that
surround follicles on multiple sides while 90 degrees scaffolds have an open
porosity that limits follicle-scaffold interaction. As the amount of scaffold
interaction increases, follicle spreading is limited and survival increases.
Follicle-seeded scaffolds become highly vascularized and ovarian function is
fully restored when implanted in surgically sterilized mice. Moreover, pups are
born through natural mating and thrive through maternal lactation. These findings
present an in vivo functional ovarian implant designed with 3D printing, and
indicate that scaffold pore architecture is a critical variable in additively
manufactured scaffold design for functional tissue engineering.
PMID- 28509900
TI - Altered expression of BDNF, BDNF pro-peptide and their precursor proBDNF in brain
and liver tissues from psychiatric disorders: rethinking the brain-liver axis.
AB - Brain-derived neurotrophic factor (BDNF) has a role in the pathophysiology of
psychiatric disorders. The precursor proBDNF is converted to mature BDNF and BDNF
pro-peptide, the N-terminal fragment of proBDNF; however, the precise function of
these proteins in psychiatric disorders is unknown. We sought to determine
whether expression of these proteins is altered in the brain and peripheral
tissues from patients with psychiatric disorders. We measured protein expression
of proBDNF, mature BDNF and BDNF pro-peptide in the parietal cortex, cerebellum,
liver and spleen from control, major depressive disorder (MDD), schizophrenia
(SZ) and bipolar disorder (BD) groups. The levels of mature BDNF in the parietal
cortex from MDD, SZ and BD groups were significantly lower than the control
group, whereas the levels of BDNF pro-peptide in this area were significantly
higher than controls. In contrast, the levels of proBDNF and BDNF pro-peptide in
the cerebellum of MDD, SZ and BD groups were significantly lower than controls.
Moreover, the levels of mature BDNF from the livers of MDD, SZ and BD groups were
significantly higher than the control group. The levels of mature BDNF in the
spleen did not differ among the four groups. Interestingly, there was a negative
correlation between mature BDNF in the parietal cortex and mature BDNF in the
liver in all the subjects. These findings suggest that abnormalities in the
production of mature BDNF and BDNF pro-peptide in the brain and liver might have
a role in the pathophysiology of psychiatric disorders, indicating a brain-liver
axis in psychiatric disorders.
PMID- 28509901
TI - A continuum of genetic liability for minor and major depression.
AB - The recent success of a large genome-wide association (GWA) study-analysing 130
620 major depression cases and 347 620 controls-in identifying the first single
nucleotide polymorphism (SNP) loci robustly associated with major depression in
Europeans confirms that immense sample sizes are required to identify risk loci
for depression. Given the phenotypic similarity between major depressive disorder
(MDD) and the less severe minor depressive disorder (MiDD), we hypothesised that
broadening the case definition to include MiDD may be an efficient approach to
increase sample sizes in GWA studies of depression. By analysing two large twin
pair cohorts, we show that minor depression and major depression lie on a single
genetic continuum, with major depression being more severe but not aetiologically
distinct from minor depression. Furthermore, we estimate heritabilities of 37%
for minor depression, 46% for major depression and 48% for minor or major
depression in a cohort of older adults (aged 50-92). However, the heritability of
minor or major depression was estimated at 40% in a cohort of younger adults
(aged 23-38). Moreover, two robust major depression-risk SNPs nominally
associated with major depression in our Australian GWA data set produced more
significant evidence for association with minor or major depression. Hence,
broadening the case phenotype in GWA studies to include subthreshold definitions,
such as MiDD, should facilitate the identification of additional genetic risk
loci for depression.
PMID- 28509902
TI - A latent genetic subtype of major depression identified by whole-exome genotyping
data in a Mexican-American cohort.
AB - Identifying data-driven subtypes of major depressive disorder (MDD) is an
important topic of psychiatric research. Currently, MDD subtypes are based on
clinically defined depression symptom patterns. Although a few data-driven
attempts have been made to identify more homogenous subgroups within MDD, other
studies have not focused on using human genetic data for MDD subtyping. Here we
used a computational strategy to identify MDD subtypes based on single-nucleotide
polymorphism genotyping data from MDD cases and controls using Hamming distance
and cluster analysis. We examined a cohort of Mexican-American participants from
Los Angeles, including MDD patients (n=203) and healthy controls (n=196). The
results in cluster trees indicate that a significant latent subtype exists in the
Mexican-American MDD group. The individuals in this hidden subtype have increased
common genetic substrates related to major depression and they also have more
anxiety and less middle insomnia, depersonalization and derealisation, and
paranoid symptoms. Advances in this line of research to validate this strategy in
other patient groups of different ethnicities will have the potential to
eventually be translated to clinical practice, with the tantalising possibility
that in the future it may be possible to refine MDD diagnosis based on genetic
data.
PMID- 28509903
TI - Gray matter anomalies in pedophiles with and without a history of child sexual
offending.
AB - Pedophilia is a psychiatric disorder that is inter-related with but distinct from
child sexual offending (CSO). Neural alterations reportedly contribute to both
pedophilia and CSO, but until now, no study has distinguished the brain
structural anomalies associated with pedophilia from those specifically
associated with CSO in pedophilic men. Using high-resolution T1-weighted brain
images and voxel-based morphometry, we analyzed the gray matter (GM) volume of
the following 219 men recruited at four acquisition sites in Germany: 58
pedophiles with a history of CSO, 60 pedophiles without any history of CSO and
101 non-pedophilic, non-offending controls to control for the effects of age,
education level, verbal IQ, sexual orientation and the acquisition site. Although
there were no differences in the relative GM volume of the brain specifically
associated with pedophilia, statistical parametric maps revealed a highly
significant and CSO-related pattern of above vs below the 'normal' GM volume in
the right temporal pole, with non-offending pedophiles exhibiting larger volumes
than offending pedophiles. Moreover, regression analysis revealed that the lower
GM volume of the dorsomedial prefrontal or anterior cingulate cortex was
associated with a higher risk of re-offending in pedophilic child molesters. We
believe our data provide the first evidence that CSO in pedophilia rather than
pedophilia alone is associated with GM anomalies and thus shed new light on the
results of previous studies on this topic. These results indicate the need for
new neurobehavioral theories on pedophilia and CSO and may be potentially useful
for treatment or prevention approaches that aim to reduce the risk of
(re)offending in pedophilia.
PMID- 28509905
TI - Crowdsourced validation of a machine-learning classification system for autism
and ADHD.
AB - Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder
(ADHD) together affect >10% of the children in the United States, but
considerable behavioral overlaps between the two disorders can often complicate
differential diagnosis. Currently, there is no screening test designed to
differentiate between the two disorders, and with waiting times from initial
suspicion to diagnosis upwards of a year, methods to quickly and accurately
assess risk for these and other developmental disorders are desperately needed.
In a previous study, we found that four machine-learning algorithms were able to
accurately (area under the curve (AUC)>0.96) distinguish ASD from ADHD using only
a small subset of items from the Social Responsiveness Scale (SRS). Here, we
expand upon our prior work by including a novel crowdsourced data set of
responses to our predefined top 15 SRS-derived questions from parents of children
with ASD (n=248) or ADHD (n=174) to improve our model's capability to generalize
to new, 'real-world' data. By mixing these novel survey data with our initial
archival sample (n=3417) and performing repeated cross-validation with
subsampling, we created a classification algorithm that performs with AUC=0.89+/
0.01 using only 15 questions.
PMID- 28509904
TI - Immunological effects of behavioral activation with exercise in major depression:
an exploratory randomized controlled trial.
AB - Major depression (MD) is associated with peripheral inflammation and increased
cardiovascular risk. Regular physical exercise can have anti-inflammatory
effects. The present study examined whether behavioral activation with exercise
affects inflammatory processes in MD. Ninety-eight patients with MD were randomly
assigned to cognitive-behavioral therapy (CBT) emphasizing exercise during
behavioral activation (CBT-E), CBT with pleasurable low-energy activities as an
active control condition (CBT-C) or a passive waiting list control group (WL).
Plasma levels of C-reactive protein (CRP), interleukin (IL)-6, IL-10,
lipopolysaccharide (LPS)-stimulated IL-6 production, and blood immune cell counts
were analyzed at baseline and weeks 8 (post-behavioral activation) and 16 (post
treatment). Thirty non-depressed age- and sex-matched controls were included to
examine potential immunological alterations in MD at baseline. Patients with MD
exhibited higher levels of CRP, higher neutrophil and monocyte counts, lower IL
10 levels and reduced LPS-stimulated IL-6 production compared to controls
(P<0.001-0.045). Multilevel modeling indicated that CBT-E was associated with
increased anti-inflammatory IL-10 at weeks 8 and 16 compared to CBT-C and WL
(P=0.004-0.018). CBT-E did not significantly affect other immunological makers in
the total sample. A subgroup analysis including patients with potentially higher
cardiovascular risk (CRP ?1 MUg ml-1) indicated that CRP was reduced in CBT-E
compared to CBT-C (P<0.007) and marginally reduced compared to WL (P<0.085) after
week 16. The present findings provide new insights into immunological effects of
behavioral treatments against depression. Behavioral activation in conjunction
with exercise may have the potential to reverse, in part, immunological
alterations in MD.
PMID- 28509907
TI - A database of georeferenced nutrient chemistry data for mountain lakes of the
Western United States.
AB - Human activities have increased atmospheric nitrogen and phosphorus deposition
rates relative to pre-industrial background. In the Western U.S., anthropogenic
nutrient deposition has increased nutrient concentrations and stimulated algal
growth in at least some remote mountain lakes. The Georeferenced Lake Nutrient
Chemistry (GLNC) Database was constructed to create a spatially-extensive lake
chemistry database needed to assess atmospheric nutrient deposition effects on
Western U.S. mountain lakes. The database includes nitrogen and phosphorus water
chemistry data spanning 1964-2015, with 148,336 chemistry results from 51,048
samples collected across 3,602 lakes in the Western U.S. Data were obtained from
public databases, government agencies, scientific literature, and researchers,
and were formatted into a consistent table structure. All data are georeferenced
to a modified version of the National Hydrography Dataset Plus version 2. The
database is transparent and reproducible; R code and input files used to format
data are provided in an appendix. The database will likely be useful to those
assessing spatial patterns of lake nutrient chemistry associated with atmospheric
deposition or other environmental stressors.
PMID- 28509906
TI - Therapeutic efficacy of atypical antipsychotic drugs by targeting multiple stress
related metabolic pathways.
AB - Schizophrenia (SZ) is considered to be a multifactorial brain disorder with
defects involving many biochemical pathways. Patients with SZ show variable
responses to current pharmacological treatments of SZ because of the
heterogeneity of this disorder. Stress has a significant role in the
pathophysiological pathways and therapeutic responses of SZ. Atypical
antipsychotic drugs (AAPDs) can modulate the stress response of the hypothalamic
pituitary-adrenal (HPA) axis and exert therapeutic effects on stress by targeting
the prefrontal cortex (PFC) and hippocampus. To evaluate the effects of AAPDs
(such as clozapine, risperidone and aripiprazole) on stress, we compared
neurochemical profile variations in the PFC and hippocampus between rat models of
chronic unpredictable mild stress (CUMS) for HPA axis activation and of long-term
dexamethasone exposure (LTDE) for HPA axis inhibition, using an ultraperformance
liquid chromatography-mass spectrometry (UPLC-MS/MS)-based metabolomic approach
and a multicriteria assessment. We identified a number of stress-induced
biomarkers comprising creatine, choline, inosine, hypoxanthine, uric acid,
allantoic acid, lysophosphatidylcholines (LysoPCs), phosphatidylethanolamines
(PEs), corticosterone and progesterone. Specifically, pathway enrichment and
correlation analyses suggested that stress induces oxidative damage by disturbing
the creatine-phosphocreatine circuit and purine pathway, leading to excessive
membrane breakdown. Moreover, our data suggested that the AAPDs tested partially
restore stress-induced deficits by increasing the levels of creatine,
progesterone and PEs. Thus, the present findings provide a theoretical basis for
the hypothesis that a combined therapy using adenosine triphosphate fuel,
antioxidants and omega-3 fatty acids as supplements may have synergistic effects
on the therapeutic outcome following AAPD treatment.
PMID- 28509908
TI - Microbial contributions to the persistence of coral reefs.
AB - On contemplating the adaptive capacity of reef organisms to a rapidly changing
environment, the microbiome offers significant and greatly unrecognised
potential. Microbial symbionts contribute to the physiology, development,
immunity and behaviour of their hosts, and can respond very rapidly to changing
environmental conditions, providing a powerful mechanism for acclimatisation and
also possibly rapid evolution of coral reef holobionts. Environmentally acquired
fluctuations in the microbiome can have significant functional consequences for
the holobiont phenotype upon which selection can act. Environmentally induced
changes in microbial abundance may be analogous to host gene duplication,
symbiont switching / shuffling as a result of environmental change can either
remove or introduce raw genetic material into the holobiont; and horizontal gene
transfer can facilitate rapid evolution within microbial strains. Vertical
transmission of symbionts is a key feature of many reef holobionts and this would
enable environmentally acquired microbial traits to be faithfully passed to
future generations, ultimately facilitating microbiome-mediated transgenerational
acclimatisation (MMTA) and potentially even adaptation of reef species in a
rapidly changing climate. In this commentary, we highlight the capacity and
mechanisms for MMTA in reef species, propose a modified Price equation as a
framework for assessing MMTA and recommend future areas of research to better
understand how microorganisms contribute to the transgenerational acclimatisation
of reef organisms, which is essential if we are to reliably predict the
consequences of global change for reef ecosystems.
PMID- 28509909
TI - Experimental evolution and the dynamics of adaptation and genome evolution in
microbial populations.
AB - Evolution is an on-going process, and it can be studied experimentally in
organisms with rapid generations. My team has maintained 12 populations of
Escherichia coli in a simple laboratory environment for >25 years and 60 000
generations. We have quantified the dynamics of adaptation by natural selection,
seen some of the populations diverge into stably coexisting ecotypes, described
changes in the bacteria's mutation rate, observed the new ability to exploit a
previously untapped carbon source, characterized the dynamics of genome evolution
and used parallel evolution to identify the genetic targets of selection. I
discuss what the future might hold for this particular experiment, briefly
highlight some other microbial evolution experiments and suggest how the fields
of experimental evolution and microbial ecology might intersect going forward.
PMID- 28509911
TI - A dataset of forest biomass structure for Eurasia.
AB - The most comprehensive dataset of in situ destructive sampling measurements of
forest biomass in Eurasia have been compiled from a combination of experiments
undertaken by the authors and from scientific publications. Biomass is reported
as four components: live trees (stem, bark, branches, foliage, roots); understory
(above- and below ground); green forest floor (above- and below ground); and
coarse woody debris (snags, logs, dead branches of living trees and dead roots),
consisting of 10,351 unique records of sample plots and 9,613 sample trees from
ca 1,200 experiments for the period 1930-2014 where there is overlap between
these two datasets. The dataset also contains other forest stand parameters such
as tree species composition, average age, tree height, growing stock volume,
etc., when available. Such a dataset can be used for the development of models of
biomass structure, biomass extension factors, change detection in biomass
structure, investigations into biodiversity and species distribution and the
biodiversity-productivity relationship, as well as the assessment of the carbon
pool and its dynamics, among many others.
PMID- 28509913
TI - Optimization of a polydopamine (PD)-based coating method and polydimethylsiloxane
(PDMS) substrates for improved mouse embryonic stem cell (ESC) pluripotency
maintenance and cardiac differentiation.
AB - Myocardiocyte derived from pluripotent stem cells, such as induced pluripotent
stem cells (iPSCs) and embryonic stem cells (ESCs), is a promising cell source
for cardiac tissue engineering. Combined with microfluidic technologies, a heart
on-a-chip is very likely to be developed and function as a platform for high
throughput drug screening. Polydimethylsiloxane (PDMS) silicone elastomer is a
widely-used biomaterial for the investigation of cell-substrate interactions and
biochip fabrication. However, the intrinsic PDMS surface hydrophobicity inhibits
cell adhesion on the PDMS surface, and PDMS surface modification is required for
effective cell adhesion. Meanwhile, the formulation of PDMS also affects the
behaviors of the cells. To fabricate PDMS-based biochips for ESC pluripotency
maintenance and cardiac differentiation, PDMS surface modification and
formulation were optimized in this study. We found that a polydopamine (PD) with
gelatin coating greatly improved the ESC adhesion, proliferation and cardiac
differentiation on its surface. In addition, different PDMS substrates varied in
their surface properties, which had different impacts on ESCs, with the 40 : 1
PDMS substrate being more favorable for ESC adhesion and proliferation as well as
embryoid body (EB) attachment than the other PDMS substrates. Moreover, the ESC
pluripotency was best maintained on the 5 : 1 PDMS substrate, while the cardiac
differentiation of the ESCs was optimal on the 40 : 1 PDMS substrate. Based on
the optimized coating method and PDMS formulation, biochips with two different
designs were fabricated and evaluated. Compared to the single channels, the
multiple channels on the biochips could provide larger areas and accommodate more
nutrients to support improved ESC pluripotency maintenance and cardiac
differentiation. These results may contribute to the development of a real heart
on-a-chip for high-throughput drug screening in the future.
PMID- 28509910
TI - Convergence of gut microbiotas in the adaptive radiations of African cichlid
fishes.
AB - Ecoevolutionary dynamics of the gut microbiota at the macroscale level, that is,
in across-species comparisons, are largely driven by ecological variables and
host genotype. The repeated explosive radiations of African cichlid fishes in
distinct lakes, following a dietary diversification in a context of reduced
genetic diversity, provide a natural setup to explore convergence, divergence and
repeatability in patterns of microbiota dynamics as a function of the host diet,
phylogeny and environment. Here we characterized by 16S rRNA amplicon sequencing
the gut microbiota of 29 cichlid species from two distinct lakes/radiations
(Tanganyika and Barombi Mbo) and across a broad dietary and phylogenetic range.
Within each lake, a significant deviation between a carnivorous and herbivorous
lifestyle was found. Herbivore species were characterized by an increased
bacterial taxonomic and functional diversity and converged in key compositional
and functional community aspects. Despite a significant lake effect on the
microbiota structure, this process has occurred with remarkable parallels in the
two lakes. A metabolic signature most likely explains this trend, as indicated by
a significant enrichment in herbivores/omnivores of bacterial taxa and functions
associated with fiber degradation and detoxification of plant chemical compounds.
Overall, compositional and functional aspects of the gut microbiota individually
and altogether validate and predict main cichlid dietary habits, suggesting a
fundamental role of gut bacteria in cichlid niche expansion and adaptation.
PMID- 28509912
TI - A resource on latitudinal and altitudinal clines of ecologically relevant
phenotypes of the Indian Drosophila.
AB - The unique geography of the Indian subcontinent has provided diverse natural
environments for a variety of organisms. In this region, many ecological indices
such as temperature and humidity vary predictably as a function of both latitude
and altitude; these environmental parameters significantly affect fundamental
dynamics of natural populations. Indian drosophilids are diverse in their
geographic distribution and climate tolerance, possibly as a result of climatic
adaptation. These associations with environmental parameters are further
reflected in a large number of clines that have been reported for various fitness
traits along these geographical ranges. This unique amalgamation of environmental
variability and genetic diversity make the subcontinent an ecological laboratory
for studying evolution in action. We assembled data collected over the last 20
years on the geographical clines for various phenotypic traits in several species
of drosophilids and present a web-resource on Indian-Drosophila (
http://www.indian-drosophila.org/). The clinal data on ecologically relevant
phenotypes of Indian drosophilids will be useful in addressing questions related
to future challenges in biodiversity and ecosystems in this region.
PMID- 28509916
TI - Systematic variation of thiophene substituents in photochromic spiropyrans.
AB - Spiropyrans are notable among different classes of photochromic compounds due to
their large structural and electronic transformation upon isomerization. In order
to parlay the electronic differences associated with the two isomeric forms into
a materials based switch, the spiropyran ultimately requires a covalent
attachment through a conjugated pathway. In this work a synthetic method was
developed to incorporate spiropyran (SP) into thiophene based materials. A series
of compounds with a systematic variation of substituents were synthesized (SP-T,
SP-T-Br, SP-T-T, SP-T-T-T and SP-T-T-T-T-SP) and their photochromism in both
polar (methanol) and non-polar (toluene) solvents were studied. These compounds
showed a systematic variation of photochromic properties.
PMID- 28509917
TI - Effect of mTHPC-mediated photodynamic therapy on 5-fluorouracil resistant human
colorectal cancer cells.
AB - The primary or acquired cancer chemoresistance is a major problem in the
treatment of cancer patients. It could be overcome by non-overlapping treatment
regimens such as photodynamic therapy (PDT). PDT is based on the oxidation of
cellular components which occurs when a light-excited photosensitizer generates
reactive oxygen species (ROS). In this study the effect of mTHPC mediated PDT
(mTHPC-PDT) on 5-FU resistant colorectal cancer (CRC) cells HCT116 was
investigated. The results show that mTHPC-PDT overcomes 5-FU resistance and is
effective against chemoresistant colorectal carcinoma cells.
PMID- 28509919
TI - Resistive switching of Sn-doped In2O3/HfO2 core-shell nanowire: geometry
architecture engineering for nonvolatile memory.
AB - Core-shell NWs offer an innovative approach to achieve nanoscale metal-insulator
metal (MIM) heterostructures along the wire radial direction, realizing three
dimensional geometry architecture rather than planar type thin film devices. This
work demonstrated the tunable resistive switching characteristics of ITO/HfO2
core-shell nanowires with controllable shell thicknesses by the atomic layer
deposition (ALD) process for the first time. Compared to planar HfO2 thin film
device configuration, ITO/HfO2 core-shell nanowire shows a prominent resistive
memory behavior, including lower power consumption with a smaller SET voltage of
~0.6 V and better switching voltage uniformity with variations (standard
deviation(sigma)/mean value (MU)) of VSET and VRESET from 0.38 to 0.14 and from
0.33 to 0.05 for ITO/HfO2 core-shell nanowire and planar HfO2 thin film,
respectively. In addition, endurance over 103 cycles resulting from the local
electric field enhancement can be achieved, which is attributed to geometry
architecture engineering. The concept of geometry architecture engineering
provides a promising strategy to modify the electric-field distribution for
solving the non-uniformity issue of future RRAM.
PMID- 28509920
TI - Insights into chemoselectivity principles in metal oxide affinity chromatography
using tailored nanocast metal oxide microspheres and mass spectrometry-based
phosphoproteomics.
AB - The ability to comprehensively characterize biological samples, including tissues
and body fluids, opens up new possibilities to diagnose and treat diseases and to
better understand fundamental biological processes. For this purpose, suitable
experimental workflows need to be designed. In this context, materials with
particular chemoselective properties are used for the enrichment of certain
classes of (bio)molecules. Metal oxides such as titanium dioxide have become the
materials of choice for the large-scale study of protein phosphorylation in
phosphoproteomics. Despite their widespread use, the main factors influencing
their performance (for example, affinity and specificity) are not completely
understood. This understanding is, however, crucial to develop improved materials
and methods. Here, we used the nanocasting method to prepare microspheres of
seven metal oxides with comparable textural properties, allowing an objective
comparison of the materials and their binding properties. We evaluated these
materials with samples of different complexity, ranging from synthetic peptides
to whole cell lysates, using liquid chromatography-tandem mass spectrometry as a
readout. A set of more than 7000 identified phosphopeptides allowed us to study
differences between the metal oxide sorbents in detail. Importantly, the
performance of the affinity materials was found to be mainly correlated with the
oxides' isoelectric points (IEPs), with the materials that enriched the highest
number of phosphopeptides having an IEP of around 6. This included the widely
used TiO2 and ZrO2, but also In2O3 that was not previously known to possess
affinity to phosphates. This finding supports the conclusion that the IEP has a
stronger influence than the particular type of metal oxide and contrasts earlier
reports that compared a limited number of materials with often unknown textural
properties. Taken together, we introduce new metal oxides suitable for
phosphopeptide enrichment, provide deeper insight into the properties that affect
their performance, and offer a strategy to optimize enrichment protocols and
materials.
PMID- 28509921
TI - Bright red-emitting pyrene derivatives with a large Stokes shift for nucleus
staining.
AB - A highly fluorescent red-emitting pyrene derivative was synthesized and found to
exhibit a large Stokes shift (lambdaem ~ 610 nm, Deltalambda ~ 130 nm, Deltanu ~
4597 cm-1). The probe molecule showed remarkable selectivity to stain the nucleus
in both live and fixed cells, with higher sensitivity than commercial dye DRAQ5.
PMID- 28509922
TI - Phosphine-catalyzed Friedel-Crafts reaction of naphthols with para-quinone
methides: expedient access to triarylmethanes.
AB - We developed a novel phosphine-catalyzed Friedel-Crafts reaction of naphthols
with para-quinone methides (p-QMs). This reaction provided a promising method for
the synthesis of triarylmethanes, which widely exist in natural products and in
molecules which have been shown to have biological and pharmacological activity.
PMID- 28509923
TI - Enantioselective alkynylation of N-sulfonyl alpha-ketiminoesters via a Friedel
Crafts alkylation strategy.
AB - Enantioselective alkynylation of cyclic N-sulfonyl alpha-ketiminoesters with
terminal alkynes was developed by using an Ni(ClO4)2/(R)-DTBM-Segphos complex as
a catalyst. A range of propargylic amides bearing quaternary stereocenters were
afforded in excellent enantioselectivities (up to 97% ee). Theoretical studies
revealed that this reaction proceeded via a Friedel-Crafts-type reaction pathway.
PMID- 28509918
TI - Generation and manipulation of hydrogel microcapsules by droplet-based
microfluidics for mammalian cell culture.
AB - Hydrogel microcapsules provide miniaturized and biocompatible niches for three
dimensional (3D) in vitro cell culture. They can be easily generated by droplet
based microfluidics with tunable size, morphology, and biochemical properties.
Therefore, microfluidic generation and manipulation of cell-laden microcapsules
can be used for 3D cell culture to mimic the in vivo environment towards
applications in tissue engineering and high throughput drug screening. In this
review of recent advances mainly since 2010, we will first introduce general
characteristics of droplet-based microfluidic devices for cell encapsulation with
an emphasis on the fluid dynamics of droplet breakup and internal mixing as they
directly influence microcapsule's size and structure. We will then discuss two on
chip manipulation strategies: sorting and extraction from oil into aqueous phase,
which can be integrated into droplet-based microfluidics and significantly
improve the qualities of cell-laden hydrogel microcapsules. Finally, we will
review various applications of hydrogel microencapsulation for 3D in vitro
culture on cell growth and proliferation, stem cell differentiation, tissue
development, and co-culture of different types of cells.
PMID- 28509924
TI - Multilayered intercalation of 1-octanol into Brodie graphite oxide.
AB - Multilayered intercalation of 1-octanol into the structure of Brodie graphite
oxide (B-GO) was studied as a function of temperature and pressure. Reversible
phase transition with the addition/removal of one layer of 1-octanol was found at
265 K by means of X-ray Diffraction (XRD) and Differential Scanning Calorimetry
(DSC). The same transition was observed at ambient temperature upon a pressure
increase above 0.6 GPa. This transition was interpreted as an incongruent melting
of the low temperature/high pressure B-GO intercalated structure with five layers
of 1-octanol parallel to GO sheets (L-solvate), resulting in the formation of a
four-layered structure that is stable under ambient conditions (A-solvate).
Vacuum heating allows the removal of 1-octanol from the A-solvate layer by layer,
while distinct sets of (00l) reflections are observed for three-, two-, and one
layered solvate phases. Step by step removal of the 1-octanol layers results in
changes of distance between graphene oxide planes by ~4.5 A. This experiment
proved that both L- and A-solvates are structures with layers of 1-octanol
parallel to GO planes. Unusual intercalation with up to five distinct layers of 1
octanol is remarkably different from the behaviour of small alcohol molecules
(methanol and ethanol), which intercalate B-GO structure with only one layer
under ambient conditions and a maximum of two layers at lower temperatures or
higher pressures. The data presented in this study make it possible to rule out a
change in the orientation of alcohol molecules from parallel to perpendicular to
the GO planes, as suggested in the 1960s to explain larger expansion of the GO
lattice due to swelling with larger alcohols.
PMID- 28509925
TI - Palladium(0)-catalyzed [2 + 2 + 1] cyclization of 1,6-enynes with vinyl bromides:
a highly diastereoselective synthesis of tetrahydro-1H-cyclopenta[c]furans
bearing two quaternary carbon centers.
AB - A new cascade process has been accomplished for the synthesis of tetrahydro-1H
cyclopenta[c]furans through palladium-catalyzed [2 + 2 + 1] cyclization of 1,6
enynes with vinyl bromides. Notably, the key feature of this transformation is
the use of vinyl bromides as the C1 building block. Various functionalized
tetrahydro-1H-cyclopenta[c]furans bearing two quaternary carbon centers could be
obtained in good yields with excellent diastereoselectivities.
PMID- 28509927
TI - Tuning morphological architectures generated through living supramolecular
assembly of a helical foldamer end-capped with two complementary nucleobases.
AB - Two appropriately functionalized nucleobases, thymine and adenine, have been
covalently linked at the N- and C-termini, respectively, of two alpha
aminoisobutyric acid-rich helical peptide foldamers, aiming at driving self
assembly through complementary recognition. A crystal-state analysis (by X-ray
diffraction) on the shorter, achiral foldamer 1 unambiguously shows that
adeninethymine base pairing, through Watson-Crick intermolecular H-bonding, does
take place between either end of each peptide molecule. In the crystals, pi
stacking between base pairs is also observed. Evidence for time-dependent
foldameroldamer associations for the longer, chiral foldamer 2 in solution is
provided by circular dichroism measurements. The self-assembly of foldamer 2,
through living supramolecular polymerization, eventually leads to the formation
of twisted fibers. Such a supramolecular organization can be affected by addition
of either pristine adenine or thymine, that acts as a "terminator" by selectively
matching a pairing nucleobase at one end of the foldamer. The co-assembly of
foldamer 2 with a porphyrin-derivatized thymine, under appropriate experimental
conditions, leads to the formation of vesicles which, in turn, can be converted
to the fiber morphology by changing the environmental polarity. Conversely,
dendrimeric, star polymer-like microstructures are generated when the
supramolecular assembly of foldamer 2 is seeded by adenine-capped gold
nanoparticles.
PMID- 28509928
TI - Highly stable nanostructured membrane electrode assembly based on Pt/Nb2O5
nanobelts with reduced platinum loading for proton exchange membrane fuel cells.
AB - Proton exchange membrane fuel cells are promising candidates for the next
generation power sources; however, poor durability and high cost impede their
widespread application. To address this dilemma, a nanostructured membrane
electrode assembly (MEA) based on Pt/Nb2O5 nanobelts (NBs) was constructed
through hydrothermal synthesis and the physical vapour deposition method.
Pt/Nb2O5 NBs were directly aligned with Nafion membrane without ionomer as a
binder. The prepared catalyst layer is ultrathin and has ultralow Pt loading. A
single cell performance of 5.80 kW gPt-1 (cathode) and 12.03 kW gPt-1 (anode) was
achieved by the Pt/Nb2O5 NBs-based MEA (66.0 MUgPt cm-2). The accelerated
durability test indicates that the Pt/Nb2O5 NBs-based MEA is far more stable than
conventional Pt/C-based MEA.
PMID- 28509929
TI - Borinic acid-catalyzed stereo- and site-selective synthesis of beta
glycosylceramides.
AB - A method for activation of unprotected ceramides towards stereo- and site
selective glycosylation is described. Two-point binding of a diarylborinic acid
catalyst to the ceramide accelerates its reactions with 'armed' glycosyl
methanesulfonate donors, resulting in the formation of a beta-glycosidic linkage
at the primary OH group.
PMID- 28509930
TI - Elucidation of inhibitor-binding pockets of d-amino acid oxidase using docking
simulation and N-sulfanylethylanilide-based labeling technology.
AB - Because of the relevance of d-serine (d-Ser) to schizophrenia, inhibitors of d
amino acid oxidase (DAO), which catalyzes degradation of d-Ser in the presence of
flavin adenine dinucleotide (FAD), are expected to be anti-schizophrenia
therapeutics. In this study, binding pockets of DAO to its inhibitor 4-bromo-3
nitrobenzoic acid were searched by combining in silico docking simulation and
labeling experiments employing an N-sulfanylethylanilide-based labeling
technology that we have developed. The results clearly demonstrated that there
are two binding pockets: one is shared with d-Ser and FAD, and the other is an
unexpected cleft between the subunits of a DAO dimer. These findings will provide
insight to aid the development of new DAO inhibitors. In addition, it was also
proved that our labeling technology could be applicable to elucidate the binding
pockets of proteins.
PMID- 28509932
TI - Synthesis and activation potential of an open shell diphosphine.
AB - A paramagnetic WIII alkyne complex bearing free terminal diphenylphosphino groups
at the side-on coordinated alkyne was synthesized using a stepwise template
strategy. This moderately stable metal supported open shell diphosphine shows an
unprecedented spontaneous splitting of nitric oxide providing a WII-eta2
C2{P(NH2)Ph2}{P(O)Ph2}+ complex featuring an amino phosphonium and a phosphine
oxide substituent.
PMID- 28509933
TI - Combined use of AFM and soft X-ray microscopy to reveal fibres' internalization
in mesothelial cells.
AB - Nanotoxicology and nanomedicine investigations often require the probing of nano
objects such as fibres and particles in biological samples and cells, whilst
internalization and intracellular destiny are the main issues for in vitro
cellular studies. Various high resolution microscopy techniques are well suited
for providing this highly sought-after information. However, sample preparation,
nanomaterial composition and sectioning challenges make it often difficult to
establish whether the fibres or particles have been internalized or they are
simply overlaying or underlying the biological matter. In this paper we suggest a
novel suitable combination of two different microscopic techniques to reveal in
intact cells the uptake of asbestos fibres by mesothelial cells. After exposure
to asbestos fibres and fixation, cells were first analysed under the AFM
instrument and then imaged under the TwinMic soft X-ray microscope at Elettra
Sincrotrone. The suggested approach combines standard soft X-ray microscopy
imaging and AFM microscopy, with a common non-invasive sample preparation
protocol which drastically reduces the experimental uncertainty and provides a
quick and definitive answer to the nanoparticle cellular and tissue uptake.
PMID- 28509935
TI - Utilization of Bone Wax as a Marker for Spatial Orientation in Intraoperative
Magnetic Resonance Imaging.
PMID- 28509934
TI - The role of the prefrontal cortex in freezing of gait in Parkinson's disease:
insights from a deep repetitive transcranial magnetic stimulation exploratory
study.
AB - Freezing of Gait (FOG) is one of the most debilitating gait impairments in
Parkinson's disease (PD), leading to increased fall risk and reduced health
related quality of life. The utility of parkinsonian medications is often limited
in the case of FOG and it frequently becomes dopamine resistant. Recent studies
have suggested that pre-frontal cortex (PFC) dysfunction contributes to FOG;
however, most previous findings provide only indirect evidence. To better
understand the role of the PFC, we aimed to investigate the impact of high
frequency, deep, repetitive transcranial magnetic stimulation (drTMS) of the
medial PFC on FOG and its mediators. Nine patients with advanced PD participated
in a randomized, cross-over exploratory study. We applied drTMS over the medial
PFC for 16 weeks, with real and sham conditions; each condition included an
intensive (i.e., 3 times a week) phase and a maintenance (once a week) phase.
Scores on a FOG-provoking test, the motor part of the Unified Parkinson's Disease
Rating Scale, and gait variability significantly improved after real drTMS, but
not after the sham condition. Self-report of FOG severity and cognitive scores
did not improve. Due to discomfort and pain during treatment, two patients
dropped out and the study was halted. These initial findings support the cause
and-effect role of the pre-frontal cortex in FOG among patients with PD. Due to
the small sample size, findings should be interpreted cautiously. Further studies
are needed to more fully assess the role of the medial PFC in the underlying
mechanism of FOG and the possibility of using non-invasive brain stimulation to
modify FOG.
PMID- 28509936
TI - Penetrating Osseous Spicules Causing High-Flow Ventral CSF Leaks in the Setting
of Relatively Low BMI : A Preliminary Study.
AB - OBJECTIVE/BACKGROUND: We have anecdotally observed patients with high-flow
ventral cerebrospinal fluid (CSF) leaks resulting from penetrating osseous
spicules or calcified discs to be relatively thin. The purpose of this study was
to explore the validity of this observation and determine if a potential
association exists between low body mass index (BMI) and high-flow spinal ventral
CSF leaks resulting from such dura-penetrating lesions. METHODS: Sixteen
consecutive patients with precisely localized high-flow ventral spinal CSF leaks
on dynamic myelography were identified. The cause of the CSF leak was determined.
The BMI on the date nearest to and within 2 weeks of myelography was recorded.
Utilizing exact sign test, the body mass index was compared to the average BMI
from the National Health and Nutrition Examination Survey (Centers for Disease
Control), matched to sex and age-range. RESULTS: The cohort consisted of 10 males
(63%) and 6 females with a mean age of 54 years (range 37-72 years). In all
patients, a spiculated osteophyte/calcified disc was identified at the site of
the leak. Fourteen patients (88%) had a BMI below the matched national average,
while only two patients (13%) had values above the national average (p = 0.004).
CONCLUSIONS: Patients with high-flow ventral CSF leaks resulting from spiculated
osteophyte or calcified disc as identified by dynamic myelography are more likely
to have a BMI below the U.S. national average, matched for gender and age-range.
This exploratory analysis requires confirmation as well as further
characterization of potential pathophysiologic mechanisms and impact on
radiographic and clinical assessments.
PMID- 28509937
TI - Next generation sequencing is informing phenotype: a TP53 example.
AB - The increased availability of next generation sequencing (NGS) and multi gene
panel testing has resulted in more frequent TP53 testing of families that do not
meet classic testing criteria. We investigated testing criteria, family history
and result outcome in a cohort of Irish probands undergoing TP53 full sequencing.
All TP53 test requests processed through the national genetic testing laboratory
between 2012 and 2014 were retrospectively reviewed. Personal and family cancer
histories were collected, including tumour type and age at diagnosis, from two
adult cancer genetic services in Ireland. Association between Li Fraumeni
syndrome (LFS) or Li Fraumeni like syndrome (LFL) criteria and test result was
examined. One hundred and 35 TP53 test requests were identified. Family history
data and test results were available on 123 of the TP53 test requests (118
female; 5 male). 59/123 (48%) did not meet classic LFS or LFL criteria. Two
individuals from this group harboured pathogenic TP53 mutations, giving a 3%
mutation detection rate in those not meeting testing criteria. Both were female
and had a personal history of early onset bilateral breast cancer with no
reported LFS cancers in the family. 64/123 (52%) met LFS or LFL criteria and were
all TP53 negative. 37/64 (57.8%) met Chompret criteria, 19/64 (29.7%) met Eeles
and 7/64 (10.9%) met Eeles and Chompret and 1/64 (1.6%) met Classic LFS criteria.
Stringent testing criteria miss germline mutations in TP53. Broadening the
criteria for TP53 testing may improve our understanding of the phenotype and
penetrance in the association syndrome.
PMID- 28509938
TI - [Urethral (indwelling or intermittent) or suprapubic routes for short-term
catheterisation in hospitalized adults].
PMID- 28509939
TI - Bioremoval of lead using Pennisetum purpureum augmented with Enterobacter cloacae
VITPASJ1: A pot culture approach.
AB - Lead is a toxic heavy metal discharged into the ecosystem from various
industries. Biological remediation strategies have been effective in the
bioremoval of lead. In our current study, a phytobacterial system using
Pennisetum purpureum along with lead-resistant bacterium (LRB) was employed for
the uptake of lead. The LRB was obtained from lead-contaminated sites. The
isolate VITPASJ1 was found to be highly tolerant to lead and was identified as an
effective plant growth-promoting bacterium. The 16S rRNA sequencing revealed
VITPASJ1 to be the closest neighbour of Enterobacter cloacae. The lead-resistant
gene pbrA in the plant and the bacterium were amplified using a specific primer.
The uptake of lead was studied by phytoremediation and rhizoremediation set-ups
where the soil was supplemented with various concentrations of lead (50, 100, 150
mg/kg). The plants were uprooted at regular intervals, and the translocation of
lead into the plant was determined by atomic absorption spectroscopy. The root
length, shoot height and chlorophyll content were found to be higher in the
rhizoremediation set-up when compared to the phytoremediation set-up. The
scanning electron microscopic micrographs gave a clear picture of increased
tissue damage in the root and shoot of the phytoremediation set-up as compared to
the rhizoremediation set-up with LRB.
PMID- 28509940
TI - Medico-legal assessment of methamphetamine and amphetamine serum concentrations
what can we learn from survived intoxications?
AB - Medico-legal experts are increasingly enlisted to assess the methamphetamine and
amphetamine serum concentrations after a criminal offense. However, since
criminal users rarely provide useful information to medico-legal experts
regarding the substances abused, when the substance(s) was/were used, dose of
ingestion tools are needed to interpret the analytical data, which can be used as
objective evidence in such cases. A comparative series of methamphetamine and
amphetamine serum concentrations were used to analyze the frequency of
concentrations, to determine methamphetamine/amphetamine concentration ratios,
and prove them as a tool to distinguish pure methamphetamine from mixed
amphetamine/methamphetamine ingestion. Additionally, two cases of survived
accidental methamphetamine intoxication, resulting from ingestion smuggling which
was longitudinally monitored, and pharmacokinetic parameters were assessed. In a
series of 628 samples where the most frequent concentration of methamphetamine
exceeded the therapeutic level, there was a strong correlation suggesting pure
methamphetamine consumption, when the ratios of methamphetamine/amphetamine
concentrations were within the range between 3 and 10. In the two cases of
methamphetamine bodypacking, the relevant serum concentrations of methamphetamine
and amphetamine, which could be measured up to 9 days after ingestion, indicated
a decrease of the methamphetamine/amphetamine ratios in an exponential manner.
However, the ratios were not always within the range between 3 and 10. Lastly,
the course of the serum concentrations suggested an increase of the apparent
elimination half-life of methamphetamine. In terms of the objective evidence
required in criminal law, calculating methamphetamine/amphetamine concentration
ratio is not a suitable to means to distinguish pure methamphetamine intake and
that of mixed amphetamine/methamphetamine abuse in an individual case. Instead,
methamphetamine high serum concentrations and the possible increase in apparent
elimination half-life suggest that an extended detection period may be used to
distinguish between "illicit use" as compared to "therapeutic use" of
methamphetamine.
PMID- 28509941
TI - Effects of perceived job insecurity on depression, suicide ideation, and decline
in self-rated health in Korea: a population-based panel study.
AB - PURPOSE: To investigate the effects of job security on new development of
depressive episode, suicide ideation, and decline in self-rated health. METHODS:
Data from the Korea Welfare Panel Study from 2012 to 2015 were analysed. A total
of 2912 waged workers self-assessed their depressive episode, suicide ideation,
and health annually by answering the questionnaire. Participants were divided
into three groups according to the level of job security: high, intermediate and
low. To evaluate the influence of job security, we performed survival analysis
after stratification by gender with adjustment for covariates. The result was
further stratified by whether the respondent was the head of household. RESULTS:
After adjusting for covariates, men in low job security group showed
significantly higher hazard ratios (HRs) for depression (HR 1.27, 95% CI 1.01
1.60), suicide ideation (HR 3.25, 95% CI 1.72-6.16), and decline in self-rated
health (HR 1.73, 95% CI 1.16-2.59). Women showed significantly higher HR of
depression in the intermediate (HR 1.37, 95% CI 1.01-1.87) and low (HR 1.50, 95%
CI 1.12-1.99) job security group. Male head of household with low job security
showed significantly higher HR of depression, suicide ideation, and decline in
self-rated health. Non-head-of-household women with intermediate and low job
security showed higher risk of depression than those with high job security.
CONCLUSIONS: We found that perceived job insecurity is associated with the new
development of depressive episode, suicide ideation, and decline in self-rated
health.
PMID- 28509942
TI - Biomolecular information gained through in vitro evolution.
AB - An in vitro evolution is a simplified Darwinian evolution in well-controlled
surroundings. This evolution process can be modeled as a hill-climbing or
adaptive walk on a fitness landscape in sequence space. The evolving molecular
system gains at least two kinds of information originating from the converged
sequences and the fitness increment of the evolving biopolymer as the adaptive
walker. These two represent two aspects of the biomolecular information, its
extent and its content, respectively. Here, we review studies related to
formulation of the "content" and "extent" of biomolecular information. The two
aspects are interconnected through physicochemical properties of the biopolymer,
contrary to the case of conventional information, which seems to be independent
of matter. The interconnection was analyzed based on the analogy between the
evolution process and thermodynamics. The linear combination of the two by a
temperature-like fluctuation factor resulted in a free-energy-like monotonically
increasing function during the evolution process.
PMID- 28509943
TI - New factors contributing to dynamic calcium regulation in the skeletal muscle
triad-a crowded place.
AB - Skeletal muscle is a highly organized tissue that has to be optimized for fast
signalling events conveying electrical excitation to contractile response. The
site of electro-chemico-mechanical coupling is the skeletal muscle triad where
two membrane systems, the extracellular t-tubules and the intracellular
sarcoplasmic reticulum, come into very close contact. Structure fits function
here and the signalling proteins DHPR and RyR1 were the first to be discovered to
bridge this gap in a conformational coupling arrangement. Since then, however,
new proteins and more signalling cascades have been identified just in the last
decade, adding more diversity and fine tuning to the regulation of excitation
contraction coupling (ECC) and control over Ca2+ store content. The concept of
Ca2+ entry into working skeletal muscle has become attractive again with the
experimental evidence summarized in this review. Store-operated Ca2+ entry
(SOCE), excitation-coupled Ca2+ entry (ECCE), action-potential-activated Ca2+
current (APACC), and retrograde EC-coupling (ECC) are new concepts additional to
the conventional orthograde ECC; they have provided fascinating new insights into
muscle physiology. In this review, we discuss the discovery of these pathways,
their potential roles, and the signalling proteins involved that show that the
triad may become a crowded place in time.
PMID- 28509945
TI - Ant-mediated indirect negative effects of aphids on spider mites living on the
same plant.
AB - Some aphid species are known to have mutualistic relationships with tending ants;
that is, the aphids supply the ants with honeydew and are protected by the ants.
Although spider mites and honeydew-producing aphids often live on the same host
plant, it has not previously been determined whether the ants tending these
aphids affect spider mite survival. Using replicated microcosms, each containing
an artificial ant nest, we compared experimentally the survival of two-spotted
spider mites on kidney bean plants with and without cowpea aphids. Our results
showed significantly fewer spider mites on plants with aphids, indicating that
spider mites were preyed upon by ants tending aphids. On the other hand, there
was no detectable plant-mediated indirect effect of aphids on mite performance in
the microcosms. Therefore, we conclude that aphids indirectly reduced the
survival of spider mites living on the same host plant via their tending ants.
Nonetheless, spider mites did not avoid settling on plant leaves infested with
aphids.
PMID- 28509944
TI - The physics of flagellar motion of E. coli during chemotaxis.
AB - Flagellar motion has been an active area of study right from the discovery of
bacterial chemotaxis in 1882. During chemotaxis, E. coli moves with the help of
helical flagella in an aquatic environment. Helical flagella are rotated in
clockwise or counterclockwise direction using reversible flagellar motors
situated at the base of each flagellum. The swimming of E. coli is characterized
by a low Reynolds number that is unique and time reversible. The random motion of
E. coli is influenced by the viscosity of the fluid and the Brownian motion of
molecules of fluid, chemoattractants, and chemorepellants. This paper reviews the
literature about the physics involved in the propulsion mechanism of E. coli.
Starting from the resistive-force theory, various theories on flagellar
hydrodynamics are critically reviewed. Expressions for drag force, elastic force
and velocity of flagellar elements are derived. By taking the elastic nature of
flagella into account, linear and nonlinear equations of motions are derived and
their solutions are presented.
PMID- 28509946
TI - The multi-morbid old brain.
PMID- 28509947
TI - [Arboviruses also have an American dream].
AB - Some arboviruses that originated in the Old World have been introduced by humans
into the American continent. The first of them was the yellow fever virus, coming
from the West African coast with slaves in the 17th-19th centuries, followed by
dengue viruses, which were always prevalent within the Americas. Next was theWest
Nile virus, introduced in New York in 1999, that spread in only a few years over
the whole continent. Then, Chikungunya virus arrived on Saint Martin Island in
2013 after its outbreak in Polynesia; it is now widespread in the Caribbean
Islands and on the American continent from the United States to Brazil. Finally,
Zika virus, already active in Asia and in the South Pacific region, was
introduced in Brazil and spread between the southern part of United States and
south Brazil. These unexpected emergences are the consequence of the
generalization of transoceanic trading; so, it is humans who are truly
responsible for such transportation of viruses from the African and Asian
continents. The mechanisms of virus establishment in unusual ecosystems have to
be analyzed in order to understand the conditions for the circulation of the
viruses, which supposes an adaptation to new hosts and vectors that are sometimes
local species (like Culex vectors of West Nile virus) but mainly previously
introduced mosquitoes (like Aedes aegypti and/or Aedes albopictus). Over time,
all these vectors developed a strong anthropophily and, most of them, a
remarkable adaptation to urban environment; hence, these arboviruses can
disseminate both in rural and urban context. This type of arboviral emergences
will certainly continue in the following years and we must imperatively develop
preventive strategies by detecting virus mutations with capacity for emergence,
enhancing the sensibility and rapidity of epidemiological surveillance, and
becoming ready to face such events that cause a truly international health
crisis.
PMID- 28509950
TI - [Erratum to: Posterior cruciate ligament injuries].
PMID- 28509948
TI - Discussion on "A randomized clinical trial of ultrasound-guided infra-clavicular
cannulation of the subclavian vein in cardiac surgical patients: short-axis
versus long-axis approach".
PMID- 28509949
TI - Palliative care in the ICU of 2050: past is prologue.
PMID- 28509951
TI - Costs and benefits of omnivore-mediated plant protection: effects of plant
feeding on Salix growth more detrimental than expected.
AB - Predators can decrease herbivore damage to plants, and this is often assumed to
be beneficial to plant growth/reproduction without actual quantification.
Moreover, previous studies have been biased towards strict carnivores and
neglected the role of omnivorous predators in prey-suppression. Here, we examined
the costs (reduction in growth) and benefits (increase in growth) of enemy
mediated plant protection via the omnivorous (prey and plant-feeding) Orthotylus
marginalis, relative to herbivory by a detrimental insect pest of Salix spp.
plantations, the beetle Phratora vulgatissima. In a first experiment, we compared
the cost of adult beetle versus omnivore nymph plant-feeding, and assessed the
(non-) additive effects of the two types of damage. In a second experiment, we
quantified the reduction in plant damage resulting from beetle-egg feeding by
omnivorous nymphs and subsequent benefits to plants. We found that plant-feeding
by omnivores negatively affected plant growth and this effect was similar to the
cost imposed by beetle herbivory. Furthermore, simultaneous damage effects were
additive and more detrimental than individual effects. While egg-predation by
omnivore nymphs completely prevented beetle damage to plants, there was no
difference in plant growth relative to only herbivore-damaged plants and growth
was still reduced compared to control plants. Thus, despite herbivore
suppression, there was no benefit to plant growth of omnivore-mediated plant
protection and the negative effects of omnivore plant-feeding remained. These
results are a first for an omnivorous enemy, and provide novel and timely
insights on the underlying assumptions of tri-trophic associations and their use
for biocontrol of insect pests.
PMID- 28509952
TI - High-yield production of mannitol by Leuconostoc pseudomesenteroides CTCC G123
from chicory-derived inulin hydrolysate.
AB - Chicory is an agricultural plant with considerable potential as a carbohydrate
substrate for low-cost production of biochemicals. In this work, the production
of mannitol by Leuconostoc pseudomesenteroides CTCC G123 from chicory-derived
inulin hydrolysate was investigated. The bioconversion process initially suffered
from the leakage of fructose to the phosphoketolase pathway, resulting in a low
mannitol yield. When inulin hydrolysate was supplemented with glucose as a
substrate for mannitol production in combination with aeration induction and
nicotinic acid induced redox modulation strategies, the mannitol yield greatly
improved. Under these conditions, significant improvement in the glucose
consumption rate, intracellular NADH levels and mannitol dehydrogenase specific
activity were observed, with mannitol production increasing from 64.6 to 88.1 g/L
and overall yield increase from 0.69 to 0.94 g/g. This work demonstrated an
efficient method for the production of mannitol from inulin hydrolysate with a
high overall yield.
PMID- 28509953
TI - Hyalinizing Clear Cell Carcinoma of the Tonsil: A Case Report.
AB - Hyalinzing clear cell carcinoma is a rare tumor of the oral cavity and is even
more rarely located in the tonsil. Here, we present a case report of a
pedunculated tonsillar mass in a nearly asymptomatic patient that was present for
2 years prior to removal. Complete surgical excision was achieved and no adjuvant
therapy was recommended. We include a discussion of this rare pathology and its
typical clinical presentation and course.
PMID- 28509954
TI - Evidence in the human of a hypotensive and a bradycardic effect after mouth
opening maintained for 10 min.
AB - PURPOSE: We have recently shown that in humans submaximal mouth opening
associated with partial masticatory movements for 10 min is followed by a small
but significant and prolonged reduction of blood pressure and heart rate. We here
report the effects of a fixed mouth opener. METHODS: In 22 seated normotensive
volunteers the effect on blood pressure and heart rate was studied in randomized
order after fixed mandibular extension and after a control procedure consisting
in keeping a stick between the incisor teeth (both for 10 min). Automated
recordings every 10 min were done for 40 min before and 120 min following the
procedure. RESULTS: Two-way ANOVA for repeated measures on absolute values
(actual recordings) and on changes from baseline revealed that, compared to
controls, systolic, diastolic and mean blood pressure and heart rate were
significantly lower after mandibular extension. Compared to controls, mandibular
extension induced an average blood pressure drop of 2.88 mmHg (systolic), 2.55
mmHg (diastolic) and 2.42 mmHg (mean) over the entire observation period. The
average decline over the central part of the observation period (30th to 80th
min) was, respectively, of 3.62, 3.70 and 3.61 mmHg. The decrements of heart rate
were of 2.11 and 2.66 beats per min. All these differences were statistically
significant. The hypotensive and bradycardic responses persisted for 70-120 min.
CONCLUSIONS: This study shows that, in normotensives, a single fixed submaximal
mouth opening for 10 min is followed by prolonged albeit small reductions of
blood pressure and heart rate.
PMID- 28509955
TI - Volunteers' Experiences Delivering a Community-University Chronic Disease Health
Awareness Program for South Asian Older Adults.
AB - Volunteers and voluntary organizations can connect preventative health care
programs to communities and may play an important role in addressing the health
needs of older adults. Despite this, tensions may exist in the structures that
drive volunteers and voluntary organizations representing immigrant communities
to provide unpaid labour to augment and supplement health care services.
Furthermore, organizational challenges may exist for community agencies relying
on volunteers to sustain a health screening and education program. The
intervention program was led by one voluntary agency specifically for South Asian
communities in partnership with the university and five local organizations. This
paper draws on volunteer surveys (n = 22) and key informant interviews (n = 12)
to detail volunteer experiences providing this intervention. Volunteers were
university students and other community volunteers. A total of 810 adults
participated in the intervention within the Greater Toronto Area, Ontario, Canada
between October 2014 and June 2016. We found that volunteers often used their
experience as a 'stepping stone' position to other education or work. They also
gained from the knowledge and used it to educate themselves and their family
members and friends. This paper provides a critical reflection on the role of
volunteers in a preventative and educational healthcare intervention program for
older adults from the South Asian community. Tensions exist when relying on
volunteer labour for the implementation of preventative community health care
programming and must be explored to ensure program sustainability as well as
equity within the health care system.
PMID- 28509956
TI - Classical protein kinases C are regulated by concerted interaction with lipids:
the importance of phosphatidylinositol-4,5-bisphosphate.
AB - Classical protein kinase C (PKC) enzymes are known to be important factors in
cell physiology both in terms of health and disease. They are activated by
triggering signals that induce their translocation to membranes. The consensus
view is that several secondary messengers are involved in this activation, such
as cytosolic Ca2+ and diacylglycerol. Cytosolic Ca2+ bridges the C2 domain to
anionic phospholipids as phosphatidylserine in the membrane, and diacylglycerol
binds to the C1 domain. Both diacylglycerol and the increase in Ca2+
concentration are assumed to arise from the extracellular signal that triggers
the hydrolysis of phosphatidylinositol-4,5-bisphosphate. However, results
obtained during the last decade indicate that this phosphoinositide itself is
also responsible for modulating classical PKC activity and its localization in
the plasma membrane.
PMID- 28509957
TI - Calcium channels and synaptic transmission in familial hemiplegic migraine type 1
animal models.
AB - One of the outstanding developments in clinical neurology has been the
identification of ion channel mutations as the origin of a wide variety of
inherited disorders like migraine, epilepsy, and ataxia. The study of several
channelopathies has provided crucial insights into the molecular mechanisms,
pathogenesis, and therapeutic approaches to complex neurological diseases. This
review addresses the mutations underlying familial hemiplegic migraine (FHM) with
particular interest in Cav2.1 (i.e., P/Q-type) voltage-activated Ca2+ channel FHM
type-1 mutations (FHM1). Transgenic mice harboring the human pathogenic FHM1
mutation R192Q or S218L (KI) have been used as models to study neurotransmission
at several central and peripheral synapses. FHM1 KI mice are a powerful tool to
explore presynaptic regulation associated with expression of Cav2.1 channels.
FHM1 Cav2.1 channels activate at more hyperpolarizing potentials and show an
increased open probability. These biophysical alterations may lead to a gain-of
function on synaptic transmission depending upon factors such as action potential
waveform and/or Cav2.1 splice variants and auxiliary subunits. Analysis of FHM
knock-in mouse models has demonstrated a deficient regulation of the cortical
excitation/inhibition (E/I) balance. The resulting excessive increases in
cortical excitation may be the mechanisms that underlie abnormal sensory
processing together with an increase in the susceptibility to cortical spreading
depression (CSD). Increasing evidence from FHM KI animal studies support the idea
that CSD, the underlying mechanism of aura, can activate trigeminal nociception,
and thus trigger the headache mechanisms.
PMID- 28509959
TI - Membrane changes under oxidative stress: the impact of oxidized lipids.
AB - Studying photosensitized oxidation of unsaturated phospholipids is of importance
for understanding the basic processes underlying photodynamic therapy, photoaging
and many other biological dysfunctions. In this review we show that the giant
unilamellar vesicle, when used as a simplified model of biological membranes, is
a powerful tool to investigate how in situ photogenerated oxidative species
impact the phospholipid bilayer. The extent of membrane damage can be modulated
by choosing a specific photosensitizer (PS) which is activated by light
irradiation and can react by either type I and or type II mechanism. We will show
that type II PS generates only singlet oxygen which reacts to the phospholipid
acyl double bond. The byproduct thus formed is a lipid hydroperoxide which
accumulates in the membrane as a function of singlet oxygen production and
induces an increase in its area without significantly affecting membrane
permeability. The presence of a lipid hydroperoxide can also play an important
role in the formation of the lipid domain for mimetic plasma membranes. Lipid
hydroperoxides can be also transformed in shortened chain compounds, such as
aldehydes and carboxylic acids, in the presence of a PS that reacts via the type
I mechanism. The presence of such byproducts may form hydrophilic pores in the
membrane for moderate oxidative stress or promote membrane disruption for massive
oxidation. Our results provide a new tool to explore membrane response to an
oxidative stress and may have implications in biological signaling of redox
misbalance.
PMID- 28509958
TI - Receptor-ligand molecular docking.
AB - Docking methodology aims to predict the experimental binding modes and affinities
of small molecules within the binding site of particular receptor targets and is
currently used as a standard computational tool in drug design for lead compound
optimisation and in virtual screening studies to find novel biologically active
molecules. The basic tools of a docking methodology include a search algorithm
and an energy scoring function for generating and evaluating ligand poses. In
this review, we present the search algorithms and scoring functions most commonly
used in current molecular docking methods that focus on protein-ligand
applications. We summarise the main topics and recent computational and
methodological advances in protein-ligand docking. Protein flexibility, multiple
ligand binding modes and the free-energy landscape profile for binding affinity
prediction are important and interconnected challenges to be overcome by further
methodological developments in the docking field.
PMID- 28509960
TI - Pathological implications of nucleic acid interactions with proteins associated
with neurodegenerative diseases.
AB - Protein misfolding disorders (PMDs) refer to a group of diseases related to the
misfolding of particular proteins that aggregate and deposit in the cells and
tissues of humans and other mammals. The mechanisms that trigger protein
misfolding and aggregation are still not fully understood. Increasing
experimental evidence indicates that abnormal interactions between PMD-related
proteins and nucleic acids (NAs) can induce conformational changes. Here, we
discuss these protein-NA interactions and address the role of deoxyribonucleic
(DNA) and ribonucleic (RNA) acid molecules in the conformational conversion of
different proteins that aggregate in PMDs, such as Alzheimer's, Parkinson's, and
prion diseases. Studies on the affinity, stability, and specificity of proteins
involved in neurodegenerative diseases and NAs are specifically addressed. A
landscape of reciprocal effects resulting from the binding of prion proteins,
amyloid-beta peptides, tau proteins, huntingtin, and alpha-synuclein are
presented here to clarify the possible role of NAs, not only as encoders of
genetic information but also in triggering PMDs.
PMID- 28509961
TI - IL-4: an important cytokine in determining the fate of T cells.
AB - The pleiotropic effect of cytokines has been well documented, but the effects
triggered by unique cytokines in different T cell types are still under
investigation. The most relevant findings on the influence of interleukin-4 (IL
4) on T cell activation, differentiation, proliferation, and survival of
different T cell types are discussed in this review. The main aim of our study
was to correlate the observed effect with the corresponding molecular mechanism
induced on IL-4/IL-4R interaction, in an effort to understand how the same
extracellular stimuli can trigger a wide spectrum of signaling pathways leading
to different responses in each T cell type.
PMID- 28509963
TI - Electric dipole moments of the fluorescent probes Prodan and Laurdan:
experimental and theoretical evaluations.
AB - Several experimental and theoretical approaches can be used for a comprehensive
understanding of solvent effects on the electronic structure of solutes. In this
review, we revisit the influence of solvents on the electronic structure of the
fluorescent probes Prodan and Laurdan, focusing on their electric dipole moments.
These biologically used probes were synthesized to be sensitive to the
environment polarity. However, their solvent-dependent electronic structures are
still a matter of discussion in the literature. The absorption and emission
spectra of Prodan and Laurdan in different solvents indicate that the two probes
have very similar electronic structures in both the ground and excited states.
Theoretical calculations confirm that their electronic ground states are very
much alike. In this review, we discuss the electric dipole moments of the ground
and excited states calculated using the widely applied Lippert-Mataga equation,
using both spherical and spheroid prolate cavities for the solute. The dimensions
of the cavity were found to be crucial for the calculated dipole moments. These
values are compared to those obtained by quantum mechanics calculations,
considering Prodan in vacuum, in a polarizable continuum solvent, and using a
hybrid quantum mechanics-molecular mechanics methodology. Based on the
theoretical approaches it is evident that the Prodan dipole moment can change
even in the absence of solute-solvent-specific interactions, which is not taken
into consideration with the experimental Lippert-Mataga method. Moreover, in
water, for electric dipole moment calculations, it is fundamental to consider
hydrogen-bonded molecules.
PMID- 28509962
TI - Thiol redox biochemistry: insights from computer simulations.
AB - Thiol redox chemical reactions play a key role in a variety of physiological
processes, mainly due to the presence of low-molecular-weight thiols and cysteine
residues in proteins involved in catalysis and regulation. Specifically, the
subtle sensitivity of thiol reactivity to the environment makes the use of
simulation techniques extremely valuable for obtaining microscopic insights. In
this work we review the application of classical and quantum-mechanical atomistic
simulation tools to the investigation of selected relevant issues in thiol redox
biochemistry, such as investigations on (1) the protonation state of cysteine in
protein, (2) two-electron oxidation of thiols by hydroperoxides, chloramines, and
hypochlorous acid, (3) mechanistic and kinetics aspects of the de novo formation
of disulfide bonds and thiol-disulfide exchange, (4) formation of sulfenamides,
(5) formation of nitrosothiols and transnitrosation reactions, and (6) one
electron oxidation pathways.
PMID- 28509967
TI - Successful Latin American initiatives in biophysics.
PMID- 28509966
TI - Rate of solute incorporation to liposomes evaluated from encapsulated enzymes
activities.
AB - There are numerous studies on systems comprising an enzyme encapsulated in
unilamellar liposomes and its substrate initially present in the external aqueous
media. Most of these studies are focused on enzyme stability and activity in a
restricted media. However, the rate of the process is also determined by the
capacity of the substrate to permeate towards the liposome inner pool. In spite
of this, there are few studies aimed at a quantitative evaluation of the
substrate permeation rate and its lifetime inside the liposome pool. In the
present work, we describe, in terms of a very simple mechanism, the permeation of
glucose and hydrogen peroxide in DPPC unilamellar liposomes. To this aim, we
evaluated the rate of the process employing encapsulated glucose oxidase and
catalase in the kinetic diffusion controlled limit. Under this condition, the
rate of the process becomes zero order in the enzyme and allows a direct
evaluation of the rate constant for the permeation process and the lifetime of a
substrate molecule incorporated into the liposome inner pool.
PMID- 28509965
TI - Antimony transport mechanisms in resistant leishmania parasites.
AB - Antimonial compounds have been used for more than a century in the treatment of
the parasitic disease leishmaniasis. Although pentavalent antimonials are still
first-line drugs in several developing countries, this class of drugs is no
longer recommended in the Indian sub-continent because of the emergence of drug
resistance. The precise mechanisms involved in the resistance of leishmania
parasites to antimony are still subject to debate. It is now well documented that
drug resistance in leishmania parasites is a multifactorial phenomenon involving
multiple genes whose expression pattern synergistically leads to the resistance
phenotype. The reduction of intracellular antimony accumulation is a frequent
change observed in resistant leishmania cells; however, no comprehensive
transport model has been presented so far to explain this change and its
contribution to Leishmania resistance. The present review firstly covers the
actual knowledge on the metabolism of antimonial drugs, the mechanisms of their
transmembrane transport and intracellular processing in Leishmania. It further
describes both the functional and molecular changes associated with Sb resistance
in this organism. Possible transport models based on the actual knowledge are
then presented, as well as their functional implications. Biophysical and
pharmacological strategies are finally proposed for the precise identification of
the transport pathways.
PMID- 28509969
TI - Epidemiology of prostate cancer.
PMID- 28509970
TI - Testis cancer: some problems still remain unsolved.
PMID- 28509968
TI - Sleep problems in children with attention-deficit hyperactivity disorder:
associations with parenting style and sleep hygiene.
AB - We aimed to examine the association between sleep problems and parenting and
sleep hygiene in children with attention-deficit/hyperactivity disorder (ADHD).
Participants included 5-13-year-old children with DSM 5 defined ADHD and a parent
reported moderate-to-severe sleep problem (N = 361). Sleep was assessed using the
parent-reported Children's Sleep Habits Questionnaire. Parents also completed
checklists assessing sleep hygiene, parenting consistency, and parenting warmth.
Linear regression established prediction models controlling for confounding
variables including child age and sex, ADHD symptom severity, comorbidities,
medication use, and socio-demographic factors. More consistent parenting was
associated with decreased bedtime resistance (beta = -0.16) and decreased sleep
anxiety (beta = -0.14), while greater parental warmth was associated with
increased parasomnias (beta = +0.18) and sleep anxiety (beta = +0.13). Poorer
sleep hygiene was associated with increased bedtime resistance (beta = +0.20),
increased daytime sleepiness (beta = +0.12), and increased sleep duration
problems (beta = +0.13). In conclusion, sleep hygiene and parenting are important
modifiable factors independently associated with sleep problems in children with
ADHD. These factors should be considered in the management of sleep problems in
children with ADHD.
PMID- 28509971
TI - Description of Chryseobacterium timonianum sp. nov., isolated from a patient with
pneumonia.
AB - Using a polyphasic taxonomic strategy, an aerobic, Gram-negative, non-motile,
yellow pigmented rod isolated from a sputum sample of a patient with pneumonia
was characterised. This bacterial strain, designated G972T, could not be
identified by our systematic MALDI-TOF screening on a MicroFlex. This led to the
sequencing of the 16S rRNA gene, which shows 98.57% sequence identity with that
of Chryseobacterium indologenes 16777T, the phylogenetic closely related type
strain of a species with standing in nomenclature, which putatively classifies it
as a new species. The major cell fatty acids were identified as 13-methyl
tetradecanoic acid (61%), 3-hydroxy-heptadecanoic acid (16%) and 15-methyl-11
hexadecenoic acid (11%). D-glucose, D-mannose, aesculin, D-maltose, D-trehalose,
and gentibiose are the main carbon source. Digital DNA-DNA hybridization (dDDH)
estimation and average nucleotide identity values (ANI) of the strain G972T
against genomes of the type strains of related species ranged between 18.9 and
32.8% and between 71.46 and 83.61%, respectively, thus confirming again the new
species status of the strain. Here, we describe the characteristics of this
organism, complete genome sequence and annotation. The 5,390,132 bp size genome
contains 4867 protein-coding genes, 89 RNAs (three genes are 5S rRNA, one gene is
16S rRNA, one gene is 23S rRNA and 84 tRNAs) with 35.51% GC content. Finally, on
the basis of these polyphasic data, consisting of phenotypic and genomic
analyses, we conclude that strain strain G972T (= DSM 103388T = CSUR P2233T)
represents a novel species for which we propose the name Chryseobacterium
timonianum. The 16S rRNA and genome sequences are available in GenBank database
under accession numbers LT161886 and FJVD00000000.
PMID- 28509973
TI - Molecular mechanisms of inherited thoracic aortic disease - from gene variant to
surgical aneurysm.
AB - Aortic dissection is a catastrophic event that has a high mortality rate.
Thoracic aortic aneurysms are the clinically silent precursor that confers an
increased risk of acute aortic dissection. There are several gene mutations that
have been identified in key structural and regulatory proteins within the aortic
wall that predispose to thoracic aneurysm formation. The most common and well
characterised of these is the FBN1 gene mutation that is known to cause Marfan
syndrome. Others less well-known mutations include TGF-beta1 and TGF-beta2
receptor mutations that cause Loeys-Dietz syndrome, Col3A1 mutations causing
Ehlers-Danlos Type 4 syndrome and Smad3 and-4, ACTA2 and MYHII mutations that
cause familial thoracic aortic aneurysm and dissection. Despite the variation in
the proteins affected by these genetic mutations, there is a unifying
pathological end point of medial degeneration within the wall of the aorta
characterised by vascular smooth muscle cell loss, fragmentation and loss of
elastic fibers, and accumulation of proteoglycans and glycosaminoglycans within
vascular smooth muscle cell-depleted areas of the aortic media. Our understanding
of these mutations and their post-translational effects has led to a greater
understanding of the pathophysiology that underlies thoracic aortic aneurysm
formation. Despite this, there are still many unanswered questions regarding the
molecular mechanisms. Further elucidation of the signalling pathways will help us
identify targets that may be suitable modifiers to enhance treatment of this
often fatal condition.
PMID- 28509972
TI - Cardiac stem cells: translation to human studies.
AB - The discovery of multiple classes of cardiac progenitor cells in the adult
mammalian heart has generated hope for their use as a therapeutic in heart
failure. However, successful results from animal models have not always yielded
similar findings in human studies. Recent Phase I/II trials of c-Kit (SCIPIO) and
cardiosphere-based (CADUCEUS) cardiac progenitor cells have demonstrated safety
and some therapeutic efficacy. Gaps remain in our understanding of the origins,
function and relationships between the different progenitor cell families, many
of which are heterogeneous populations with overlapping definitions. Another
challenge lies in the limitations of small animal models in replicating the human
heart. Cryopreserved human cardiac tissue provides a readily available source of
cardiac progenitor cells and may help address these questions. We review
important findings and relative unknowns of the main classes of cardiac
progenitor cells, highlighting differences between animal and human studies.
PMID- 28509964
TI - The excitation-contraction coupling mechanism in skeletal muscle.
AB - First coined by Alexander Sandow in 1952, the term excitation-contraction
coupling (ECC) describes the rapid communication between electrical events
occurring in the plasma membrane of skeletal muscle fibres and Ca2+ release from
the SR, which leads to contraction. The sequence of events in twitch skeletal
muscle involves: (1) initiation and propagation of an action potential along the
plasma membrane, (2) spread of the potential throughout the transverse tubule
system (T-tubule system), (3) dihydropyridine receptors (DHPR)-mediated detection
of changes in membrane potential, (4) allosteric interaction between DHPR and
sarcoplasmic reticulum (SR) ryanodine receptors (RyR), (5) release of Ca2+ from
the SR and transient increase of Ca2+ concentration in the myoplasm, (6)
activation of the myoplasmic Ca2+ buffering system and the contractile apparatus,
followed by (7) Ca2+ disappearance from the myoplasm mediated mainly by its
reuptake by the SR through the SR Ca2+ adenosine triphosphatase (SERCA), and
under several conditions movement to the mitochondria and extrusion by the
Na+/Ca2+ exchanger (NCX). In this text, we review the basics of ECC in skeletal
muscle and the techniques used to study it. Moreover, we highlight some recent
advances and point out gaps in knowledge on particular issues related to ECC such
as (1) DHPR-RyR molecular interaction, (2) differences regarding fibre types, (3)
its alteration during muscle fatigue, (4) the role of mitochondria and store
operated Ca2+ entry in the general ECC sequence, (5) contractile potentiators,
and (6) Ca2+ sparks.
PMID- 28509975
TI - Adaptations of cytoarchitecture in human dilated cardiomyopathy.
AB - Hypertrophic cardiomyopathy is characterised by a histological phenotype of
myocyte disarray, but heart tissue samples from patients with dilated
cardiomyopathy (DCM) often look comparatively similar to those from healthy
individuals apart from conspicuous regions of fibrosis and necrosis. We have
previously investigated subcellular alterations in the cytoarchitecture of mouse
models of dilated cardiomyopathy and found that both the organisation and
composition of the intercalated disc, i.e. the specialised type of cell-cell
contact in the heart, is altered. There is also is a change in the composition of
the M-band of the sarcomere due to an expression shift towards the more
extensible embryonic heart (EH)-myomesin isoform. Analysis of human samples from
the Sydney Human Heart Tissue Bank have revealed similar structural findings and
also provided evidence for a dramatic change in overall cardiomyocyte size
control, which has also been seen in the mouse. Together these changes in
cytoarchitecture probably contribute to the decreased functional output that is
seen in DCM.
PMID- 28509976
TI - Mechanisms of SR calcium release in healthy and failing human hearts.
AB - Normal heart contraction and rhythm relies on the proper flow of calcium ions
(Ca2+) into cardiac cells and between their intracellular organelles, and any
disruption can lead to arrhythmia and sudden cardiac death. Electrical excitation
of the surface membrane activates voltage-dependent L-type Ca2+ channels to open
and allow Ca2+ to enter the cytoplasm. The subsequent increase in cytoplasmic
Ca2+ concentration activates calcium release channels (RyR2) located at
specialised Ca2+ release sites in the sarcoplasmic reticulum (SR), which serves
as an intracellular Ca2+ store. Animal models have provided valuable insights
into how intracellular Ca2+ transport mechanisms are altered in human heart
failure. The aim of this review is to examine how Ca2+ release sites are
remodelled in heart failure and how this affects intracellular Ca2+ transport
with an emphasis on Ca2+ release mechanisms in the SR. Current knowledge on how
heart failure alters the regulation of RyR2 by Ca2+ and Mg2+ and how these
mechanisms control the activity of RyR2 in the confines of the Ca2+ release sites
is reviewed.
PMID- 28509977
TI - The role of super-relaxed myosin in skeletal and cardiac muscle.
AB - The super-relaxed (SRX) state of myosin was only recently reported in striated
muscle. It is characterised by a sub-population of myosin heads with a highly
inhibited rate of ATP turnover. Myosin heads in the SRX state are bound to each
other along the thick filament core producing a highly ordered arrangement. Upon
activation, these heads project into the interfilament space where they can bind
to the actin filaments. Thus far, the population and lifetimes of myosin heads in
the SRX state have been characterised in rabbit cardiac, and fast and slow
skeletal muscle, as well as in the skeletal muscle of the tarantula. These
studies suggest that the role of SRX in cardiac and skeletal muscle regulation is
tailored to their specific functions. In skeletal muscle, the SRX modulates the
resting metabolic rate. Cardiac SRX represents a "reserve" of inactive myosin
heads that may protect the heart during times of stress, e.g. hypoxia and
ischaemia. These heads may also be called up when there is a sustained demand for
increased power. The SRX in cardiac muscle provides a potential target for novel
therapies.
PMID- 28509974
TI - Decoding the complex genetic causes of heart diseases using systems biology.
AB - The pace of disease gene discovery is still much slower than expected, even with
the use of cost-effective DNA sequencing and genotyping technologies. It is
increasingly clear that many inherited heart diseases have a more complex
polygenic aetiology than previously thought. Understanding the role of gene-gene
interactions, epigenetics, and non-coding regulatory regions is becoming
increasingly critical in predicting the functional consequences of genetic
mutations identified by genome-wide association studies and whole-genome or exome
sequencing. A systems biology approach is now being widely employed to
systematically discover genes that are involved in heart diseases in humans or
relevant animal models through bioinformatics. The overarching premise is that
the integration of high-quality causal gene regulatory networks (GRNs), genomics,
epigenomics, transcriptomics and other genome-wide data will greatly accelerate
the discovery of the complex genetic causes of congenital and complex heart
diseases. This review summarises state-of-the-art genomic and bioinformatics
techniques that are used in accelerating the pace of disease gene discovery in
heart diseases. Accompanying this review, we provide an interactive web-resource
for systems biology analysis of mammalian heart development and diseases,
CardiacCode ( http://CardiacCode.victorchang.edu.au/ ). CardiacCode features a
dataset of over 700 pieces of manually curated genetic or molecular perturbation
data, which enables the inference of a cardiac-specific GRN of 280 regulatory
relationships between 33 regulator genes and 129 target genes. We believe this
growing resource will fill an urgent unmet need to fully realise the true
potential of predictive and personalised genomic medicine in tackling human heart
disease.
PMID- 28509978
TI - Surgery for hypertrophic cardiomyopathy.
AB - Hypertrophic cardiomyopathy (HCM) is a genetically determined cardiac disease
characterised by otherwise unexplained myocardial hypertrophy of the left
ventricle, and may result in left ventricular outflow tract obstruction. It is
the most common cause of sudden cardiac death in young adults due to arrhythmias.
Septal myectomy is a surgical treatment for HCM with moderate to severe outflow
tract obstruction, and is indicated for patients with severe symptoms refractory
to medical therapy. The surgical approach involves obtaining access to the
interventricular septum via transaortic, transapical or transmitral approaches,
and excising a portion of the hypertrophied myocardium to relieve the outflow
tract obstruction. Large, contemporary series from centres experienced in septal
myectomy patients have demonstrated a low early mortality of <2 %, excellent long
term survival that matches the general population, and durable relief of
symptoms.
PMID- 28509979
TI - G protein-coupled receptors in cardiac biology: old and new receptors.
AB - G protein-coupled receptors (GPCRs) are seven-transmembrane-spanning proteins
that mediate cellular and physiological responses. They are critical for
cardiovascular function and are targeted for the treatment of hypertension and
heart failure. Nevertheless, current therapies only target a small fraction of
the cardiac GPCR repertoire, indicating that there are many opportunities to
investigate unappreciated aspects of heart biology. Here, we offer an update on
the contemporary view of GPCRs and the complexities of their signalling, and
review the roles of the 'classical' GPCRs in cardiovascular physiology and
disease. We then provide insights into other GPCRs that have been less
extensively studied in the heart, including orphan, odorant and taste receptors.
We contend that these novel cardiac GPCRs contribute to heart function in health
and disease and thereby offer exciting opportunities to therapeutically modulate
heart function.
PMID- 28509983
TI - Special Issue on human heart failure.
PMID- 28509985
TI - Structural and biophysical properties of the integrin-associated cytoskeletal
protein talin.
AB - Talin is a large cytoskeletal protein (2541 amino acid residues) which plays a
key role in integrin-mediated events that are crucial for cell adhesion,
migration, proliferation and survival. This review summarises recent work on the
structure of talin and on some of the structurally better defined interactions
with other proteins. The N-terminal talin head (approx. 50 kDa) consists of an
atypical FERM domain linked to a long flexible rod (approx. 220 kDa) made up of a
series of amphipathic helical bundle domains. The F3 FERM subdomain in the head
binds the cytoplasmic tail of integrins, but this interaction can be inhibited by
an interaction of F3 with a helical bundle in the talin rod, the so-called
"autoinhibited form" of the molecule. The talin rod contains a second integrin
binding site, at least two actin-binding sites and a large number of binding
sites for vinculin, which is important in reinforcing the initial integrin-actin
link mediated by talin. The vinculin binding sites are defined by hydrophobic
residues buried within helical bundles, and these must unfold to allow vinculin
binding. Recent experiments suggest that this unfolding may be mediated by
mechanical force exerted on the talin molecule by actomyosin contraction.
PMID- 28509984
TI - Spontaneous oscillatory contraction (SPOC) in cardiomyocytes.
AB - SPOC (spontaneous oscillatory contraction) is a characteristic state of the
contractile system of striated (skeletal and cardiac) muscle that exists between
the states of relaxation and contraction. For example, Ca-SPOCs occur at
physiological Ca2+ levels (pCa ~6.0), whereas ADP-SPOC occurs in the virtual
absence of Ca2+ (pCa >= 8; relaxing conditions in the presence of MgATP), but in
the presence of inorganic phosphate (Pi) and a high concentration of MgADP. The
concentration of Mg-ADP necessary for SPOC is nearly equal to or greater than the
MgATP concentration for cardiac muscle and is several times higher for skeletal
muscle. Thus, the cellular conditions for SPOC are broader in cardiac muscle than
in skeletal muscle. During these SPOCs, each sarcomere in a myofibril undergoes
length oscillation that has a saw-tooth waveform consisting of a rapid
lengthening and a slow shortening phase. The lengthening phase of one half of a
sarcomere is transmitted to the adjacent half of the sarcomere successively,
forming a propagating wave (termed a SPOC wave). The SPOC waves are synchronized
across the cardiomyocytes resulting in a visible wave of successive contractions
and relaxations termed the SPOC wave. Experimentally, the SPOC period (and
therefore the velocity of SPOC wave) is observed in demembranated cardiomyocytes
and can be prepared from a wide range of animal hearts. These periods correlate
well with the resting heartbeats of a wide range of mammals (rat, rabbit, dog,
pig and cow). Preliminary experiments showed that the SPOC properties of human
cardiomyocytes are similar to the heartbeat of a large dog or a pig. This
correlation suggests that SPOCs may play a fundamental role in the heart. Here,
we briefly summarize a range of SPOC parameters obtained experimentally, and
relate them to a theoretical model to explain those characteristics. Finally, we
discuss the possible significance of these SPOC properties in each and every
heartbeat.
PMID- 28509981
TI - Microdomain-specific localization of functional ion channels in cardiomyocytes:
an emerging concept of local regulation and remodelling.
AB - Cardiac excitation involves the generation of action potential by individual
cells and the subsequent conduction of the action potential from cell to cell
through intercellular gap junctions. Excitation of the cellular membrane results
in opening of the voltage-gated L-type calcium ion (Ca2+) channels, thereby
allowing a small amount of Ca2+ to enter the cell, which in turn triggers the
release of a much greater amount of Ca2+ from the sarcoplasmic reticulum, the
intracellular Ca2+ store, and gives rise to the systolic Ca2+ transient and
contraction. These processes are highly regulated by the autonomic nervous
system, which ensures the acute and reliable contractile function of the heart
and the short-term modulation of this function upon changes in heart rate or
workload. It has recently become evident that discrete clusters of different ion
channels and regulatory receptors are present in the sarcolemma, where they form
an interacting network and work together as a part of a macro-molecular
signalling complex which in turn allows the specificity, reliability and accuracy
of the autonomic modulation of the excitation-contraction processes by a variety
of neurohormonal pathways. Disruption in subcellular targeting of ion channels
and associated signalling proteins may contribute to the pathophysiology of a
variety of cardiac diseases, including heart failure and certain arrhythmias.
Recent methodological advances have made it possible to routinely image the
topography of live cardiomyocytes, allowing the study of clustering functional
ion channels and receptors as well as their coupling within a specific
microdomain. In this review we highlight the emerging understanding of the
functionality of distinct subcellular microdomains in cardiac myocytes (e.g. T
tubules, lipid rafts/caveolae, costameres and intercalated discs) and their
functional role in the accumulation and regulation of different subcellular
populations of sodium, Ca2+ and potassium ion channels and their contributions to
cellular signalling and cardiac pathology.
PMID- 28509982
TI - Phospholamban phosphorylation, mutation, and structural dynamics: a biophysical
approach to understanding and treating cardiomyopathy.
AB - We review the recent development of novel biochemical and spectroscopic methods
to determine the site-specific phosphorylation, expression, mutation, and
structural dynamics of phospholamban (PLB), in relation to its function
(inhibition of the cardiac calcium pump, SERCA2a), with specific focus on cardiac
physiology, pathology, and therapy. In the cardiomyocyte, SERCA2a actively
transports Ca2+ into the sarcoplasmic reticulum (SR) during relaxation (diastole)
to create the concentration gradient that drives the passive efflux of Ca2+
required for cardiac contraction (systole). Unphosphorylated PLB (U-PLB) inhibits
SERCA2a, but phosphorylation at S16 and/or T17 (producing P-PLB) changes the
structure of PLB to relieve SERCA2a inhibition. Because insufficient SERCA2a
activity is a hallmark of heart failure, SERCA2a activation, by gene therapy
(Andino et al. 2008; Fish et al. 2013; Hoshijima et al. 2002; Jessup et al. 2011)
or drug therapy (Ferrandi et al. 2013; Huang 2013; Khan et al. 2009; Rocchetti et
al. 2008; Zhang et al. 2012), is a widely sought goal for treatment of heart
failure. This review describes rational approaches to this goal. Novel
biophysical assays, using site-directed labeling and high-resolution
spectroscopy, have been developed to resolve the structural states of SERCA2a-PLB
complexes in vitro and in living cells. Novel biochemical assays, using synthetic
standards and multidimensional immunofluorescence, have been developed to
quantitate PLB expression and phosphorylation states in cells and human tissues.
The biochemical and biophysical properties of U-PLB, P-PLB, and mutant PLB will
ultimately resolve the mechanisms of loss of inhibition and gain of inhibition to
guide therapeutic development. These assays will be powerful tools for
investigating human tissue samples from the Sydney Heart Bank, for the purpose of
analyzing and diagnosing specific disorders.
PMID- 28509980
TI - The role of TGFbeta1 and LRG1 in cardiac remodelling and heart failure.
AB - Heart failure is a life-threatening condition that carries a considerable
emotional and socio-economic burden. As a result of the global increase in the
ageing population, sedentary life-style, increased prevalence of risk factors,
and improved survival from cardiovascular events, the incidence of heart failure
will continue to rise. Despite the advances in current cardiovascular therapies,
many patients are not suitable for or may not benefit from conventional
treatments. Thus, more effective therapies are required. Transforming growth
factor (TGF) beta family of cytokines is involved in heart development and dys
regulated TGFbeta signalling is commonly associated with fibrosis, aberrant
angiogenesis and accelerated progression into heart failure. Therefore, a
potential therapeutic pathway is to modulate TGFbeta signalling; however, broad
blockage of TGFbeta signalling may cause unwanted side effects due to its pivotal
role in tissue homeostasis. We found that leucine-rich alpha-2 glycoprotein 1
(LRG1) promotes blood vessel formation via regulating the context-dependent
endothelial TGFbeta signalling. This review will focus on the interaction between
LRG1 and TGFbeta signalling, their involvement in the pathogenesis of heart
failure, and the potential for LRG1 to function as a novel therapeutic target.
PMID- 28509986
TI - Structure and functions of profilins.
AB - Profilins are small actin-binding proteins found in eukaryotes and certain
viruses that are involved in cell development, cytokinesis, membrane trafficking,
and cell motility. Originally identified as an actin sequestering/binding
protein, profilin has been involved in actin polymerization dynamics. It
catalyzes the exchange of ADP/ATP in actin and increases the rate of
polymerization. Profilins also interact with polyphosphoinositides (PPI) and
proline-rich domains containing proteins. Through its interaction with PPIs,
profilin has been linked to signaling pathways between the cell membrane and the
cytoskeleton, while its role in membrane trafficking has been associated with its
interaction with proline-rich domain-containing proteins. Depending on the
organism, profilin is present in a various number of isoforms. Four isoforms of
profilin have been reported in higher organisms, while only one or two isoforms
are expressed in single-cell organisms. The affinity of these isoforms for their
ligands varies between isoforms and should therefore modulate their functions.
However, the significance and the functions of the different isoforms are not yet
fully understood. The structures of many profilin isoforms have been solved both
in the presence and the absence of actin and poly-L-proline. These structural
studies will greatly improve our understanding of the differences and
similarities between the different profilins. Structural stability studies of
different profilins are also shedding some light on our understanding of the
profilin/ligand interactions. Profilin is a multifaceted protein for which a
dramatic increase in potential functions has been found in recent years; as such,
it has been implicated in a variety of physiological and pathological processes.
PMID- 28509987
TI - Corneal collagen-its role in maintaining corneal shape and transparency.
AB - Corneal collagen has a number of properties that allow it to fulfil its role as
the main structural component within the tissue. Fibrils are narrow, uniform in
diameter and precisely organised. These properties are vital to maintain
transparency and to provide the biomechanical prerequisites necessary to sustain
shape and provide strength. This review describes the structure and arrangement
of corneal collagen from the nanoscopic to the macroscopic level, and how this
relates to the maintenance of the form and transparency of the cornea.
PMID- 28509988
TI - Vibrational spectroscopic mapping and imaging of tissues and cells.
AB - Vibrational spectroscopic mapping (point-by-point measurement) and imaging of
biological samples (cells and tissues) covering Fourier-transform infrared (FTIR)
and Raman spectroscopies has opened up many exciting new avenues to explore
biochemical architecture and processes within healthy and diseased cells and
tissues, including medical diagnostics and drug design.
PMID- 28509991
TI - Camellia sinensis increased apoptosis on U2OS osteosarcoma cells and wound
healing potential on NIH3T3 fibroblast cells.
AB - Camellia sinensis (Cs) is a plant which is rich in polyphenols and has
antioxidant, antiinflammatory, antimutagenic, anticarcinogenic and antibacterial
activities. In this study, two different methanol extracts (Cs-I and Cs-II) were
prepared from the leaf of C. sinensis in order to investigate the wound healing
and anticancer activities. Total phenolic content and antioxidant activity of the
extracts were determined. Wound healing effects of Cs extracts were evaluated by
using Masson's Trichrome Tecnique on NIH3T3 fibroblast cells. Cytotoxic and
apoptotic effects of the extracts were determined by MTT and AnnexinV-PI assays
on U2OS osteosarcoma cells. Total phenolic contents and antioxidant activities of
the extracts were almost the same. The highest concentration (60 ug/mL) of the
extracts showed significant cytotoxic and apoptotic effects on U2OS cells.
Especially, the highest apoptotic effect was determined with 60 ug/mL Cs-I
extract. Significant wound healing potential on NIH3T3 fibroblast cells were
determined especially with low extract concentrations (0.5, 1 and 5 ug/mL), while
high extract concentrations showed significant anticancer effects. As a result,
two Cs leaf extracts exhibited important apoptotic properties and both have wound
healing potential. However, the Cs-I extract was found more effective on
apoptotic osteosarcoma cell death and has an increased wound healing potential
than the Cs-II extract.
PMID- 28509989
TI - The DNA sequence specificity of bleomycin cleavage in a systematically altered
DNA sequence.
AB - Bleomycin is an anti-tumour agent that is clinically used to treat several types
of cancers. Bleomycin cleaves DNA at specific DNA sequences and recent genome
wide DNA sequencing specificity data indicated that the sequence 5'-RTGT*AY
(where T* is the site of bleomycin cleavage, R is G/A and Y is T/C) is
preferentially cleaved by bleomycin in human cells. Based on this DNA sequence,
we constructed a plasmid clone to explore this bleomycin cleavage preference. By
systematic variation of single nucleotides in the 5'-RTGT*AY sequence, we were
able to investigate the effect of nucleotide changes on bleomycin cleavage
efficiency. We observed that the preferred consensus DNA sequence for bleomycin
cleavage in the plasmid clone was 5'-YYGT*AW (where W is A/T). The most highly
cleaved sequence was 5'-TCGT*AT and, in fact, the seven most highly cleaved
sequences conformed to the consensus sequence 5'-YYGT*AW. A comparison with
genome-wide results was also performed and while the core sequence was similar in
both environments, the surrounding nucleotides were different.
PMID- 28509992
TI - Learning about "cause" and "effect" through well-designed studies of air quality
interventions.
PMID- 28509990
TI - Transient Activation of Reprogramming Transcription Factors Using Protein
Transduction Facilitates Conversion of Human Fibroblasts Toward Cardiomyocyte
Like Cells.
AB - Derivation of cardiomyocytes directly from patients' own fibroblasts could offer
a new therapeutic approach for those with ischemic heart disease. An essential
step toward clinical application is to establish safe conversion of human
fibroblasts into a cardiac fate. Here we aimed to efficiently and safely generate
cardiomyocytes from human fibroblasts by direct delivery of reprogramming
recombinant cell permeant form of reprogramming proteins followed by cardio
inductive signals. Human fetal and adult fibroblasts were transiently exposed to
transactivator of transcription-fused recombinant OCT4, SOX2, KLF4 and c-MYC for
2 weeks and then were directly differentiated toward protein-induced
cardiomyocyte-like cells (p-iCLCs) in a cardiac fate niche, carried out by
treatment with a set of cardiogenic small molecules (sequential treatment of
Chir, and IWP-2, SB431542 and purmorphamine). The cells showed cardiac phenotype
over a period of 3 weeks without first undergoing reprogramming into or through a
pluripotent intermediate, shown by lack of expression of key pluripotency
markers. p-iCLCs exhibited cardiac features at both the gene and protein levels.
Our study provides an alternative method for the generation of p-iCLCs which
shortcut reprogramming toward allogeneic cardiomyocytes in a safe and efficient
manner and could facilitate generation of genetic material-free cardiomyocytes.
PMID- 28509993
TI - Biophysical aspects and biological implications of the interaction of
benzophenanthridine alkaloids with DNA.
AB - Benzophenanthridine alkaloids represent a very interesting and significant group
of natural products that exhibit a broad range of biological and pharmacological
properties. Among this group of alkaloids, sanguinarine, nitidine, fagaronine,
and chelerythrine have the potential to form molecular complexes with DNA
structures and have attracted recent attention for their possible clinical and
pharmacological utility. This review focuses on the interaction of these
alkaloids with polymorphic DNA structures (B-form, Z-form, HL-form, and triple
helical form) reported by several research groups employing various physical
techniques such as spectrophotometry, spectrofluorimetry, circular dichroism, NMR
spectroscopy, thermal melting, viscometry as well as thermodynamic analysis by
isothermal titration calorimetry and differential scanning calorimetry to
elucidate the mode and mechanism of action at the molecular level to determine
the structure-activity relationship. DNA binding properties of these alkaloids
are interpreted in relation to their biological activity.
PMID- 28509994
TI - Fluorescent membrane probes' behavior in lipid bilayers: insights from molecular
dynamics simulations.
AB - Fluorescence spectroscopy and microscopy have been used as tools to study
membrane biophysics for decades now. Because phospholipids are non-fluorescent,
the use of extrinsic membrane probes in this context is commonplace. Two major
points of concern arise regarding this matter, namely the incomplete
understanding of the probe behavior inside the bilayer and the perturbation of
the latter resulting from probe incorporation. To this effect, molecular dynamics
(MD) simulations, by providing detailed atomic-scale information, represent a
valuable way to characterize the location and dynamics of bilayer-inserted
membrane probes, as well as the magnitude of perturbation they induce on the host
lipid structure, and several important classes of reporter molecules have been
studied in recent years. This article reviews the state of the art of MD
simulations of bilayer-inserted fluorescent probes, focusing on the information
that has been obtained from previous studies and hinting at future perspectives
in this rapidly emerging field.
PMID- 28509995
TI - Muscle myosin filaments: cores, crowns and couplings.
AB - Myosin filaments in muscle, carrying the ATPase myosin heads that interact with
actin filaments to produce force and movement, come in multiple varieties
depending on species and functional need, but most are based on a common
structural theme. The now successful journeys to solve the ultrastructures of
many of these myosin filaments, at least at modest resolution, have not been
without their false starts and erroneous sidetracks, but the picture now emerging
is of both diversity in the rotational symmetries of different filaments and a
degree of commonality in the way the myosin heads are organised in resting
muscle. Some of the remaining differences may be associated with how the muscle
is regulated. Several proteins in cardiac muscle myosin filaments can carry
mutations associated with heart disease, so the elucidation of myosin filament
structure to understand the effects of these mutations has a clear and topical
clinical relevance.
PMID- 28509996
TI - Imaging mass spectrometry: principle and application.
AB - Imaging mass spectrometry (IMS) is two-dimensional mass spectrometry to visualize
the spatial distribution of biomolecules, which does not need either separation
or purification of target molecules, and enables us to monitor not only the
identification of unknown molecules but also the localization of numerous
molecules simultaneously. Among the ionization techniques, matrix assisted laser
desorption/ionization (MALDI) is one of the most generally used for IMS, which
allows the analysis of numerous biomolecules ranging over wide molecular weights.
Proper selection and preparation of matrix is essential for successful imaging
using IMS. Tandem mass spectrometry, which is referred to MSn, enables the
structural analysis of a molecule detected by the first step of IMS. Applications
of IMS were initially developed for studying proteins or peptides. At present,
however, targets of IMS research have expanded to the imaging of small endogenous
metabolites such as lipids, exogenous drug pharmacokinetics, exploring new
disease markers, and other new scientific fields. We hope that this new
technology will open a new era for biophysics.
PMID- 28509997
TI - Social Desirability Bias and Prevalence of Sexual HIV Risk Behaviors Among People
Who Use Drugs in Baltimore, Maryland: Implications for Identifying Individuals
Prone to Underreporting Sexual Risk Behaviors.
AB - The role of social desirability bias (SDB) in self-reported HIV risk behaviors
continues to be problematic. This study examined whether SDB was associated with
self-reported, via audio computer assisted self-interviewing, sexual risk
behaviors among people who use drugs. The present study was conducted among 559
participants who reported having a recent sexual partner at their 6-month visit
of a longitudinal study. Robust Poisson regression was used to model the
association between SDB and five risk behaviors. Analyses were stratified by
gender and partner type. Higher scores of SDB were associated with decreased
reporting of selling sex and having more than one sexual partner. Higher SDB
scores were associated with increased reporting of always using condoms during
oral, vaginal, and anal sex. Gender-specific differences were observed. The
inclusion of a measure of SDB in data collection, along with other strategies,
can be used to both identify and reduce self-report biases.
PMID- 28509998
TI - Influence of Side Effects on ART Adherence Among PLWH in China: The Moderator
Role of ART-Related Knowledge.
AB - Despite the medical advancements in HIV treatment, realities of side effects are
faced by people living with HIV (PLWH) who receive antiretroviral therapy (ART).
Mixed findings have been reported on the association between side effects and ART
adherence. However, few studies have explored the combined side effects and
behavior-related information on medication adherence. The aim of the current
study is to examine moderator role of ART-related knowledge between side effects
and ART adherence. A cross-sectional survey was conducted among 2987 PLWH from
October 2012 to August 2013 in China. Of the total sample, 2095 patients had
received ART and provided ART adherence. Side effects, ART-related knowledge, and
ART adherence, as well as potential covariates were assessed. The results
revealed that there was a negative relationship of side effects and ART adherence
existed among low and medium levels of ART-related knowledge, but not among high
level of knowledge. Future interventions to promote HIV medication adherence
should focus on providing behavior-related information education among PLWH.
PMID- 28510002
TI - The spin label amino acid TOAC and its uses in studies of peptides: chemical,
physicochemical, spectroscopic, and conformational aspects.
AB - We review work on the paramagnetic amino acid 2,2,6,6-tetramethyl-N-oxyl-4-amino
4-carboxylic acid, TOAC, and its applications in studies of peptides and peptide
synthesis. TOAC was the first spin label probe incorporated in peptides by means
of a peptide bond. In view of the rigid character of this cyclic molecule and its
attachment to the peptide backbone via a peptide bond, TOAC incorporation has
been very useful to analyze backbone dynamics and peptide secondary structure.
Many of these studies were performed making use of EPR spectroscopy, but other
physical techniques, such as X-ray crystallography, CD, fluorescence, NMR, and FT
IR, have been employed. The use of double-labeled synthetic peptides has allowed
the investigation of their secondary structure. A large number of studies have
focused on the interaction of peptides, both synthetic and biologically active,
with membranes. In the latter case, work has been reported on ligands and
fragments of GPCR, host defense peptides, phospholamban, and beta-amyloid. EPR
studies of macroscopically aligned samples have provided information on the
orientation of peptides in membranes. More recent studies have focused on peptide
protein and peptide-nucleic acid interactions. Moreover, TOAC has been shown to
be a valuable probe for paramagnetic relaxation enhancement NMR studies of the
interaction of labeled peptides with proteins. The growth of the number of TOAC
related publications suggests that this unnatural amino acid will find increasing
applications in the future.
PMID- 28509999
TI - Voltage sensor of ion channels and enzymes.
AB - Placed in the cell membrane (a two-dimensional environment), ion channels and
enzymes are able to sense voltage. How these proteins are able to detect the
difference in the voltage across membranes has attracted much attention, and at
times, heated debate during the last few years. Sodium, Ca2+ and K+ voltage
dependent channels have a conserved positively charged transmembrane (S4) segment
that moves in response to changes in membrane voltage. In voltage-dependent
channels, S4 forms part of a domain that crystallizes as a well-defined structure
consisting of the first four transmembrane (S1-S4) segments of the channel
forming protein, which is defined as the voltage sensor domain (VSD). The VSD is
tied to a pore domain and VSD movements are allosterically coupled to the pore
opening to various degrees, depending on the type of channel. How many charges
are moved during channel activation, how much they move, and which are the
molecular determinants that mediate the electromechanical coupling between the
VSD and the pore domains are some of the questions that we discuss here. The VSD
can function, however, as a bona fide proton channel itself, and, furthermore,
the VSD can also be a functional part of a voltage-dependent phosphatase.
PMID- 28510000
TI - Actin in striated muscle: recent insights into assembly and maintenance.
AB - Striated muscle cells are characterised by a para-crystalline arrangement of
their contractile proteins actin and myosin in sarcomeres, the basic unit of the
myofibrils. A multitude of proteins is required to build and maintain the
structure of this regular arrangement as well as to ensure regulation of
contraction and to respond to alterations in demand. This review focuses on the
actin filaments (also called thin filaments) of the sarcomere and will discuss
how they are assembled during myofibrillogenesis and in hypertrophy and how their
integrity is maintained in the working myocardium.
PMID- 28510004
TI - Non fitting based FRET-FLIM analysis approaches applied to quantify protein
protein interactions in live cells.
AB - New imaging methodologies in quantitative fluorescence microscopy and nanoscopy
have been developed in the last few years and are beginning to be extensively
applied to biological problems, such as the localization and quantification of
protein interactions. Fluorescence resonance energy transfer (FRET) detected by
fluorescence lifetime imaging microscopy (FLIM) is currently employed not only in
biophysics or chemistry but also in bio-medicine, thanks to new advancements in
technology and also new developments in data treatment. FRET-FLIM can be a very
useful tool to ascertain protein interactions occurring in single living cells.
In this review, we stress the importance of increasing the acquisition speed when
working in vivo employing Time-Domain FLIM. The development of the new
mathematical-based non-fitting methods allows the determining of the fraction of
interacting donor without the requirement of high count statistics, and thus
allows the performing of high speed acquisitions in FRET-FLIM to still be
quantitative.
PMID- 28510003
TI - SPontaneous Oscillatory Contraction (SPOC): auto-oscillations observed in
striated muscle at partial activation.
AB - Striated muscle is well known to exist in either of two states-contraction or
relaxation-under the regulation of Ca2+ concentration. Described here is a less
well-known third, intermediate state induced under conditions of partial
activation, known as SPOC (SPontaneous Oscillatory Contraction). This state is
characterised by auto-oscillation between rapid-lengthening and slow-shortening
phases. Notably, SPOC occurs in skinned muscle fibres and is therefore not the
result of fluctuating Ca2+ levels, but is rather an intrinsic and fundamental
phenomenon of the actomyosin motor. Summarised in this review are the
experimental data on SPOC and its fundamental mechanism. SPOC presents a novel
technique for studying independent communication and coordination between
sarcomeres. In cardiac muscle, this auto-oscillatory property may work in concert
with electro-chemical signalling to coordinate the heartbeat. Further, SPOC may
represent a new way of demonstrating functional defects of sarcomeres in human
heart failure.
PMID- 28510001
TI - Proteoliposomes in nanobiotechnology.
AB - Proteoliposomes are systems that mimic lipid membranes (liposomes) to which a
protein has been incorporated or inserted. During the last decade, these systems
have gained prominence as tools for biophysical studies on lipid-protein
interactions as well as for their biotechnological applications. Proteoliposomes
have a major advantage when compared with natural membrane systems, since they
can be obtained with a smaller number of lipidic (and protein) components,
facilitating the design and interpretation of certain experiments. However, they
have the disadvantage of requiring methodological standardization for
incorporation of each specific protein, and the need to verify that the
reconstitution procedure has yielded the correct orientation of the protein in
the proteoliposome system with recovery of its functional activity. In this
review, we chose two proteins under study in our laboratory to exemplify the
steps necessary for the standardization of the reconstitution of membrane
proteins in liposome systems: (1) alkaline phosphatase, a protein with a
glycosylphosphatidylinositol anchor, and (2) Na,K-ATPase, an integral membrane
protein. In these examples, we focus on the production of the specific
proteoliposomes, as well as on their biochemical and biophysical
characterization, with emphasis on studies of lipid-protein interactions. We
conclude the chapter by highlighting current prospects of this technology for
biotechnological applications, including the construction of nanosensors and of a
multi-protein nanovesicular biomimetic to study the processes of initiation of
skeletal mineralization.
PMID- 28510005
TI - Respiratory system dynamical mechanical properties: modeling in time and
frequency domain.
AB - The mechanical properties of the respiratory system are important determinants of
its function and can be severely compromised in disease. The assessment of
respiratory system mechanical properties is thus essential in the management of
some disorders as well as in the evaluation of respiratory system adaptations in
response to an acute or chronic process. Most often, lungs and chest wall are
treated as a linear dynamic system that can be expressed with differential
equations, allowing determination of the system's parameters, which will reflect
the mechanical properties. However, different models that encompass nonlinear
characteristics and also multicompartments have been used in several approaches
and most specifically in mechanically ventilated patients with acute lung injury.
Additionally, the input impedance over a range of frequencies can be assessed
with a convenient excitation method allowing the identification of the mechanical
characteristics of the central and peripheral airways as well as lung periphery
impedance. With the evolution of computational power, the airway pressure and
flow can be recorded and stored for hours, and hence continuous monitoring of the
respiratory system mechanical properties is already available in some mechanical
ventilators. This review aims to describe some of the most frequently used models
for the assessment of the respiratory system mechanical properties in both time
and frequency domain.
PMID- 28510007
TI - Response to editorial: Diagnosing carotid near-occlusion with 1-mm side-to-side
asymmetry: a tough task made too easy.
PMID- 28510006
TI - Evaluation of the DSM-5 Severity Specifier for Bulimia Nervosa in Treatment
Seeking Youth.
AB - A new severity specifier for bulimia nervosa (BN), based on the frequency of
inappropriate weight compensatory behaviours (e.g., laxative misuse, self-induced
vomiting, fasting, diuretic misuse, and excessive exercise), has been added to
the most recent (fifth) edition of the Diagnostic and Statistical Manual of
Mental Disorders (DSM-5) as a means of addressing variability and heterogeneity
in the severity of the disorder. While existing research provides support for the
DSM-5 severity specifier for BN in adult patients, evidence for its validity and
clinical utility in youth is currently lacking. To address this gap, data from
272 treatment-seeking adolescents with DSM-5 BN (94.2% female, M age = 15.3
years, SD 1.7) were analysed to examine whether these patients, sub-grouped based
on the DSM-5 severity definitions, would show meaningful differences in a broad
range of clinical variables and demographic and physical characteristics.
Analyses revealed that participants categorized with mild, moderate, severe, and
extreme severity of BN significantly differed from each other in 15 variables
regarding eating disorder pathological features and putative maintenance factors
(i.e., core low self-esteem, perfectionism, social appearance anxiety, body
surveillance, and mood intolerance), health-related quality of life and comorbid
psychiatric (i.e., affective and anxiety) disorders (large effect sizes). Between
group differences in demographics, body mass index, or age-of-BN onset were not
observed. Collectively, our findings provide support for the utility of the
frequency of inappropriate weight compensatory behaviours as a severity indicator
for BN and suggest that age-at-onset of BN is probably more disorder- than
severity-dependent. Implications for future research are outlined.
PMID- 28510008
TI - Plasma modified surfaces for covalent immobilization of functional biomolecules
in the absence of chemical linkers: towards better biosensors and a new
generation of medical implants.
AB - Plasma modification and plasma polymer deposition are valuable technologies for
the preparation of surfaces for the covalent binding of biomolecules for
applications such as biosensors, medical prostheses, and diagnostic devices as
well as surfaces for enzyme-mediated reactions. Covalency is conveniently tested
by the ability of the surface to retain the attached molecules after vigorous
washing with sodium dodecyl sulphate (SDS). Covalency is indicated if the
fraction of protein retained lies above the curve characteristic of
physisorption. Confidence in covalency is strengthened when the washing protocol
is aggressive enough to remove all adsorbed protein from a control significantly
more hydrophobic than the test surface. The use of linker chemistry to space the
molecules from the surface is in some cases beneficial. However, the use of
linker chemistry is not necessary to retain molecular function for long periods
when the polymer surface is modified by energetic bombardment. The energetic
bombardment retains hydrophilicity of the surface by crosslinking the subsurface,
and this appears to facilitate retention of protein function. Energetic
bombardment also increases the functional life of molecules immobilized and then
freeze dried on plasma-modified surfaces. Analysis of the surfaces shows that the
covalent binding mechanism is related to the presence of free radicals on the
surface and in the subsurface regions. The unpaired electrons associated with the
radicals appear to be mobile within the modified region and can diffuse to the
surface to take part in binding interactions. Proactive implantable devices can
make use of these principles of covalent attachment by seeding the surface of an
implant with a biomolecule that elicits the desired interaction with cells and
prevents undesirable responses.
PMID- 28510010
TI - Advanced magnetic resonance imaging techniques to better understand multiple
sclerosis.
AB - Magnetic resonance imaging (MRI) has considerably improved the diagnosis and
monitoring of multiple sclerosis (MS). Conventional MRI such as T2-weighted and
gadolinium-enhanced T1-weighted sequences detect focal lesions of the white
matter, damage of the blood-brain barrier, and tissue loss and inflammatory
activity within lesions. However, these conventional MRI metrics lack the
specificity required for characterizing the underlying pathophysiology,
especially diffuse damage occurring throughout the whole central nervous system.
To overcome these limitations, advanced MRI techniques have been developed to get
more sensitive and specific parameters of focal and diffuse brain damage. Among
these techniques, magnetization transfer imaging, diffusion MRI, functional MRI,
and magnetic resonance spectroscopy are the most significant. In this article, we
provide an overview of these advanced MRI techniques and their contribution to
the better characterization and understanding of MS.
PMID- 28510009
TI - Conventional myosins - unconventional functions.
AB - While the discovery of unconventional myosins raised expectations that their
actions were responsible for most aspects of actin-based cell motility, few
anticipated the wide range of cellular functions that would remain the purview of
conventional two-headed myosins. The three nonsarcomeric, cellular myosins-M2A,
M2B and M2C-participate in diverse roles including, but not limited to: neuronal
dynamics, axon guidance and synaptic transmission; endothelial cell migration;
cell adhesion, polarity, fusion and cytokinesis; vesicle trafficking and viral
egress. These three conventional myosins each take on specific, differing
functional roles during development and maturity, characteristic of each cell
lineage; exact roles depend on the developmental stage of the cell, cellular
location, upstream regulatory controls, relative isoform expression, orientation
and associated state of the actin cytoscaffolds in which these myosins operate.
Here, we discuss the separate yet related roles that characterise the actions of
M2A, M2B and M2C in various cell types and show that these conventional myosins
are responsible for functions as unconventional as any performed by
unconventional myosins.
PMID- 28510012
TI - A note on the career of Donald J Winzor.
PMID- 28510011
TI - Dynamic light scattering: a practical guide and applications in biomedical
sciences.
AB - Dynamic light scattering (DLS), also known as photon correlation spectroscopy
(PCS), is a very powerful tool for studying the diffusion behaviour of
macromolecules in solution. The diffusion coefficient, and hence the hydrodynamic
radii calculated from it, depends on the size and shape of macromolecules. In
this review, we provide evidence of the usefulness of DLS to study the
homogeneity of proteins, nucleic acids, and complexes of protein-protein or
protein-nucleic acid preparations, as well as to study protein-small molecule
interactions. Further, we provide examples of DLS's application both as a
complementary method to analytical ultracentrifugation studies and as a screening
tool to validate solution scattering models using determined hydrodynamic radii.
PMID- 28510013
TI - NMR magnetization-transfer analysis of rapid membrane transport in human
erythrocytes.
AB - Nuclear magnetic resonance (NMR) magnetization-transfer (MT) experiments provide
a convenient tool for studying rapid sub-second membrane-transport processes in
situ in metabolically active cells. These experiments are used with membrane
permeable substances when separate (resolved) NMR signals are observed from their
populations inside and outside the cells. Here, we provide a description of the
theory and practice of the most common NMR MT experiments that have been used to
study membrane-transport processes in human erythrocytes (red blood cells; RBCs).
The procedures, involved in the analysis of the experimental data for defining
mechanisms of transport, and for estimating values of kinetic parameters in the
corresponding mathematical models, are given special attention.
PMID- 28510016
TI - Big ideas from "small science".
PMID- 28510014
TI - Biosensor binding data and its applicability to the determination of active
concentration.
AB - Protein concentration data are required for understanding protein interactions
and are a prerequisite for the determination of affinity and kinetic properties.
It is vital for the judgment of protein quality and for monitoring the effect of
therapeutic agents. Protein concentration values are typically obtained by
comparison to a standard and derived from a standard curve. The use of a protein
standard is convenient, but may not give reliable results if samples and
standards behave differently. In other cases, a standard preparation may not be
available and has to be established and validated. Using surface plasmon
resonance (SPR) biosensors, an alternative concentration method is possible. This
method is called calibration-free concentration analysis (CFCA); it generates
active concentration data directly and without the use of a standard. The active
concentration of a protein is defined through its interaction with its binding
partner. This concentration can differ from the total protein concentration if
some protein fraction is incapable of binding. If a protein has several different
binding sites, active concentration data can be established for each binding site
using site-specific interaction partners. This review will focus on CFCA
analysis. It will reiterate the theory of CFCA and describe how CFCA has been
applied in different research segments. The major part of the review will,
however, try to set expectations on CFCA and discuss how CFCA can be further
developed for absolute and relative concentration measurements.
PMID- 28510017
TI - Charge matters.
PMID- 28510015
TI - Dissociative mechanism for irreversible thermal denaturation of oligomeric
proteins.
AB - Protein stability is a fundamental characteristic essential for understanding
conformational transformations of the proteins in the cell. When using protein
preparations in biotechnology and biomedicine, the problem of protein stability
is of great importance. The kinetics of denaturation of oligomeric proteins may
have characteristic properties determined by the quaternary structure. The
kinetic schemes of denaturation can include the multiple stages of conformational
transitions in the protein oligomer and stages of reversible dissociation of the
oligomer. In this case, the shape of the kinetic curve of denaturation or the
shape of the melting curve registered by differential scanning calorimetry can
vary with varying the protein concentration. The experimental data illustrating
dissociative mechanism for irreversible thermal denaturation of oligomeric
proteins have been summarized in the present review. The use of test systems
based on thermal aggregation of oligomeric proteins for screening of agents
possessing anti-aggregation activity is discussed.
PMID- 28510018
TI - A Hilly path through the thermodynamics and statistical mechanics of protein
solutions.
AB - The opus of Don Winzor in the fields of physical and analytical biochemistry is a
major component of that certain antipodean approach to this broad area of
research that blossomed in the second half of the twentieth century. The need to
formulate problems in terms of thermodynamic nonideality posed the challenge of
describing a clear route from molecular interactions to the parameters that
biochemists routinely measure. Mapping out this route required delving into the
statistical mechanics of solutions of macromolecules, and at every turn
mathematically complex, rigorous, general results that had previously been
derived previously, often by Terrell Hill, came to the fore. Central to this work
were the definition of the "thermodynamic activity", the pivotal position of the
polynomial expansion of the osmotic pressure in terms of molar concentration and
the relationship of virial coefficients to details of the forces between limited
size groups of interacting molecules. All of this was richly exploited in the
task of taking account of excluded volume and electrostatic interactions,
especially in the use of sedimentation equilibrium to determine values of
constants for molecular association reactions. Such an approach has proved
relevant to the study of molecular interactions generally, even those between the
main macromolecular solute and components of the solvent, by using techniques
such as exclusion and affinity chromatography as well as light scattering.
PMID- 28510019
TI - Six decades of research in physical biochemistry.
PMID- 28510021
TI - Molecular assembly and structure of the bacteriophage T4 tail.
AB - The tail of bacteriophage T4 undergoes large structural changes upon infection
while delivering the phage genome into the host cell. The baseplate is located at
the distal end of the contractile tail and plays a central role in transmitting
the signal to the tail sheath that the tailfibers have been adsorbed by a host
bacterium. This then triggers the sheath contraction. In order to understand the
mechanism of assembly and conformational changes of the baseplate upon infection,
we have determined the structure of an in vitro assembled baseplate through the
three-dimensional reconstruction of cryo-electron microscopy images to a
resolution of 3.8 A from electron micrographs. The atomic structure was fitted to
the baseplate structure before and after sheath contraction in order to elucidate
the conformational changes that occur after bacteriophage T4 has attached itself
to a cell surface. The structure was also used to investigate the protease
digestion of the assembly intermediates and the mutation sites of the tail genes,
resulting in a number of phenotypes.
PMID- 28510022
TI - Aspects of protein-DNA interactions: a review of quantitative thermodynamic
theory for modelling synthetic circuits utilising LacI and CI repressors, IPTG
and the reporter gene lacZ.
AB - Protein-DNA interactions are central to the control of gene expression across all
forms of life. The development of approaches to rigorously model such
interactions has often been hindered both by a lack of quantitative binding data
and by the difficulty in accounting for parameters relevant to the intracellular
situation, such as DNA looping and thermodynamic non-ideality. Here, we review
these considerations by developing a thermodynamically based mathematical model
that attempts to simulate the functioning of an Escherichia coli expression
system incorporating two of the best characterised prokaryotic DNA binding
proteins, Lac repressor and lambda CI repressor. The key aim was to reproduce
experimentally observed reporter gene activities arising from the expression of
either wild-type CI repressor or one of three positive-control CI mutants. The
model considers the role of several potentially important, but sometimes
neglected, biochemical features, including DNA looping, macromolecular crowding
and non-specific binding, and allowed us to obtain association constants for the
binding of CI and its variants to a specific operator sequence.
PMID- 28510020
TI - Foreword to 'Quantitative and analytical relations in biochemistry'-a special
issue in honour of Donald J. Winzor's 80th birthday.
AB - The purpose of this special issue is to honour Professor Donald J. Winzor's long
career as a researcher and scientific mentor, and to celebrate the milestone of
his 80th birthday. Throughout his career, Don has been renowned for his
development of clever approximations to difficult quantitative relations
governing a range of biophysical measurements. The theme of this special issue,
'Quantitative and analytical relations in biochemistry', was chosen to reflect
this aspect of Don's scientific approach.
PMID- 28510023
TI - Protein-RNA interactions: structural biology and computational modeling
techniques.
AB - RNA-binding proteins are functionally diverse within cells, being involved in RNA
metabolism, translation, DNA damage repair, and gene regulation at both the
transcriptional and post-transcriptional levels. Much has been learnt about their
interactions with RNAs through structure determination techniques and
computational modeling. This review gives an overview of the structural data
currently available for protein-RNA complexes, and discusses the technical issues
facing structural biologists working to solve their structures. The review
focuses on three techniques used to solve the 3-dimensional structure of protein
RNA complexes at atomic resolution, namely X-ray crystallography, solution
nuclear magnetic resonance (NMR) and cryo-electron microscopy (cryo-EM). The
review then focuses on the main computational modeling techniques that use these
atomic resolution data: discussing the prediction of RNA-binding sites on unbound
proteins, docking proteins, and RNAs, and modeling the molecular dynamics of the
systems. In conclusion, the review looks at the future directions this field of
research might take.
PMID- 28510025
TI - Ion channels involved in cold detection in mammals: TRP and non-TRP mechanisms.
AB - Substantial progress in understanding thermal transduction in peripheral sensory
nerve endings was achieved with the recent cloning of six thermally gated ion
channels from the TRP (transient receptor potential) super-family. Two of these
channels, TRP melastatin 8 (TRPM8) and TRP ankyrin 1 (TRPA1), are expressed in
dorsal root ganglion (DRG) and trigeminal ganglion (TG) neurons, are activated by
various degrees of cooling, and are candidates for mediating gentle cooling and
noxious cold, respectively. However, accumulating evidence suggests that more
than just these two channels are involved in cold sensing in mammals. A recent
report described a critical role of the voltage-gated tetrodotoxin-resistant
sodium channel Nav1.8 in perceiving intense cold and noxious stimuli at cold
temperatures. Other ion channels, such as two-pore domain background potassium
channels (K2P), are known to be expressed in peripheral nerves, have pronounced
temperature dependence, and may contribute to cold sensing and/or cold
hypersensitivity in pain states. This article reviews the evidence supporting a
role for each of these channels in cold transduction, focusing on their
biophysical properties, expression pattern, and modulation by pro-inflammatory
mediators.
PMID- 28510024
TI - Mineralization and non-ideality: on nature's foundry.
AB - Understanding how ions, ion-clusters and particles behave in non-ideal
environments is a fundamental question concerning planetary to atomic scales. For
biomineralization phenomena wherein diverse inorganic and organic ingredients are
present in biological media, attributing biomaterial composition and structure to
the chemistry of singular additives may not provide a holistic view of the
underlying mechanisms. Therefore, in this review, we specifically address the
consequences of physico-chemical non-ideality on mineral formation. Influences of
different forms of non-ideality such as macromolecular crowding, confinement and
liquid-like organic phases on mineral nucleation and crystallization in
biological environments are presented. Novel prospects for the additive
controlled nucleation and crystallization are accessible from this biophysical
view. In this manner, we show that non-ideal conditions significantly affect the
form, structure and composition of biogenic and biomimetic minerals.
PMID- 28510026
TI - Gene electrotransfer: from biophysical mechanisms to in vivo applications : Part
2 - In vivo developments and present clinical applications.
AB - Gene electrotransfer can be obtained not just on single cells in diluted
suspension. For more than 10 years, this is a quasi routine strategy in tissue on
the living animal and a few clinical trials have now been approved. New problems
have been brought by the close contacts of cells in tissue both on the local
field distribution and on the access of DNA to target cells. They need to be
solved to provide a further improvement in the efficacy and safety of protein
expression. There is a competition between gene transfer and cell destruction.
Nevertheless, present results are indicative that electrotransfer is a promising
approach for gene therapy. High level and long-lived expression of proteins can
be obtained in muscles. This is used for a successful method of
electrovaccination.
PMID- 28510028
TI - Creating robust, reliable, clinically relevant classifiers from spectroscopic
data.
AB - I describe in detail the intimately connected feature extraction and classifier
development stages of the data-driven Statistical Classification Strategy (SCS)
and compare them with current practice used in MR spectroscopy. We initially
created the SCS for the analysis of MR and IR spectra of biofluids and tissues,
and subsequently extended it to analyze biomedical data in general. I focus on
explaining how to extract discriminatory spectral features and create robust
classifiers that can reliably discriminate diseases and disease states. I discuss
our approach to identifying features that retain spectral identity and
provisionally relate these features, averaged subregions of the spectra, to
specific chemical entities ("metabolites"). Particular emphasis is placed on
describing the steps required to help create classifiers whose accuracy doesn't
deteriorate significantly when presented with new, unknown samples. A simple but
powerful extension of the discovered features to detect metabolite-metabolite
(feature-feature) interactions is also sketched. I contrast the advantages and
disadvantages of using either spectral signatures or explicit metabolite
concentrations derived from the spectra as sets of discriminatory features. At
present, no clear-cut preference is obvious and more objective comparisons will
be needed. Finally, I argue that clinical requirements and exigencies strongly
suggest adopting a two-phase approach to diagnosis/prognosis. In the first phase
the emphasis ought to be on providing as accurate a diagnosis as possible,
without any attempt to identify "biomarkers." That should be the goal of the
second, research phase, with a view of providing prognosis on disease
progression.
PMID- 28510030
TI - Tri-modal regulation of cardiac muscle relaxation; intracellular calcium decline,
thin filament deactivation, and cross-bridge cycling kinetics.
AB - Cardiac muscle relaxation is an essential step in the cardiac cycle. Even when
the contraction of the heart is normal and forceful, a relaxation phase that is
too slow will limit proper filling of the ventricles. Relaxation is too often
thought of as a mere passive process that follows contraction. However, many
decades of advancements in our understanding of cardiac muscle relaxation have
shown it is a highly complex and well-regulated process. In this review, we will
discuss three distinct events that can limit the rate of cardiac muscle
relaxation: the rate of intracellular calcium decline, the rate of thin-filament
de-activation, and the rate of cross-bridge cycling. Each of these processes are
directly impacted by a plethora of molecular events. In addition, these three
processes interact with each other, further complicating our understanding of
relaxation. Each of these processes is continuously modulated by the need to
couple bodily oxygen demand to cardiac output by the major cardiac physiological
regulators. Length-dependent activation, frequency-dependent activation, and beta
adrenergic regulation all directly and indirectly modulate calcium decline, thin
filament deactivation, and cross-bridge kinetics. We hope to convey our
conclusion that cardiac muscle relaxation is a process of intricate checks and
balances, and should not be thought of as a single rate-limiting step that is
regulated at a single protein level. Cardiac muscle relaxation is a system level
property that requires fundamental integration of three governing systems:
intracellular calcium decline, thin filament deactivation, and cross-bridge
cycling kinetics.
PMID- 28510027
TI - Single-molecule Forster resonance energy transfer studies of RNA structure,
dynamics and function.
AB - Single-molecule fluorescence microscopy experiments on RNA molecules brought to
light the highly complex dynamics of key biological processes, including RNA
folding, catalysis of ribozymes, ligand sensing of riboswitches and aptamers, and
protein synthesis in the ribosome. By using highly advanced biophysical
spectroscopy techniques in combination with sophisticated biochemical synthesis
approaches, molecular dynamics of individual RNA molecules can be observed in
real time and under physiological conditions in unprecedented detail that cannot
be achieved with bulk experiments. Here, we review recent advances in RNA folding
and functional studies of RNA and RNA-protein complexes addressed by using single
molecule Forster (fluorescence) resonance energy transfer (smFRET) technique.
PMID- 28510031
TI - The structure and function of thioester-containing proteins in arthropods.
AB - Thioester-containing proteins (TEPs) form an ancient and diverse family of
secreted proteins that play central roles in the innate immune response. Two
families of TEPs, complement factors and alpha2-macroglobulins, have been known
and studied in vertebrates for many years, but only in the last decade have
crystal structures become available. In the same period, the presence of two
additional classes of TEPs has been revealed in arthropods. In this review, we
discuss the common structural features TEPs and how this knowledge can be applied
to the many arthropod TEPs of unknown function. TEPs perform a wide variety of
functions that are driven by different quaternary structures and protein-protein
interactions between a common set of folded domains. A common theme is regulated
conformational change triggered by proteolysis. Structure-function analysis of
the diverse arthropod TEPs may identify not just new mechanisms in innate
immunity but also interfaces between immunity, development and cell death.
PMID- 28510029
TI - Gene electrotransfer: from biophysical mechanisms to in vivo applications : Part
1- Biophysical mechanisms.
AB - Electropulsation is one of the nonviral methods successfully used to deliver
genes into living cells in vitro and in vivo. This approach shows promise in the
field of gene and cellular therapies. The present review focuses on the processes
supporting gene electrotransfer in vitro. In the first part, we will report the
events occurring before, during, and after pulse application in the specific
field of plasmid DNA electrotransfer at the cell level. A critical discussion of
the present theoretical considerations about membrane electropermeabilization and
the transient structures involved in the plasmid uptake follows in a second part.
PMID- 28510033
TI - The Antagonistic Effect of Selenium on Cadmium-Induced Damage and mRNA Levels of
Selenoprotein Genes and Inflammatory Factors in Chicken Kidney Tissue.
AB - Selenium (Se) is a necessary trace mineral in the diet of humans and animals.
Cadmium (Cd) is a toxic heavy metal that can damage animal organs, especially the
kidneys. Antagonistic interactions between Se and Cd have been reported in
previous studies. However, little is known about the effects of Se against Cd
toxicity and on the mRNA levels of 25 selenoprotein genes and inflammatory
factors in chicken kidneys. In the current study, we fed chickens with a Se
treated, Cd-treated, or Se/Cd treated diet for 90 days. We then analyzed the mRNA
expression of inflammatory factors (including prostaglandin E synthase (PTGES),
nuclear factor-kappa B (NF-kappaB), tumor necrosis factor-alpha (TNF-alpha), and
cyclooxygenase-2 (COX-2)) and 25 selenoprotein genes (Gpx1, Gpx2, Gpx3, Gpx4,
Txnrd1, Txnrd2, Txnrd3, Dio1, Dio2, Dio3, SPS2, Sepp1, SelPb, Sep15, Selh, Seli,
Selm, Selo, Sels, Sepx1, Selu, Selk, Selw, Seln, Selt). The results demonstrated
that Cd exposure increased the Cd content in the chicken kidneys, renal tubular
epithelial cells underwent denaturation and necrosis, and the tubules became
narrow or disappeared. However, Se supplementation reduced the Cd content in
chicken kidneys and induced normal development of renal tubular epithelial cells.
In addition, we also observed that Se alleviated the Cd-induced increase in the
mRNA levels of inflammatory factors and ameliorated the Cd-induced downtrend in
the mRNA levels of 25 selenoprotein genes in chicken kidneys.
PMID- 28510034
TI - Improvement of Fabry Disease-Related Gastrointestinal Symptoms in a Significant
Proportion of Female Patients Treated with Agalsidase Beta: Data from the Fabry
Registry.
AB - Fabry disease, an X-linked inherited lysosomal storage disorder, is caused by
mutations in the gene encoding alpha-galactosidase, GLA. In patients with Fabry
disease, glycosphingolipids accumulate in various cell types, triggering a range
of cellular and tissue responses that result in a wide spectrum of organ
involvement. Although variable, gastrointestinal symptoms are among the most
common and significant early clinical manifestations; they tend to persist into
adulthood if left untreated. To further understand the effects of sustained
enzyme replacement therapy (ERT) with agalsidase beta on gastrointestinal
symptoms in heterozygotes, a data analysis of female patients enrolled in the
Fabry Registry was conducted. To be included, females of any age must have
received agalsidase beta (average dose 1.0 mg/kg every 2 weeks) for at least 2.5
years. Measured outcomes were self-reported gastrointestinal symptoms (abdominal
pain, diarrhea). Outcomes at baseline and last follow-up, and their change from
baseline to last follow-up, were assessed. Relevant data were available for 168
female patients. Mean age at the start of ERT was 43 years and mean treatment
duration 5.7 years. Baseline pre-treatment abdominal pain was reported by 45% of
females and diarrhea by 39%. At last follow-up, 31% reported abdominal pain (p <
0.01) and 27% diarrhea (p < 0.01). The results of this Fabry Registry analysis
suggest that while on sustained treatment with agalsidase beta (1.0 mg/kg every 2
weeks), both abdominal pain and diarrhea improved in many female patients with
Fabry disease.
PMID- 28510032
TI - Kidney stone analysis techniques and the role of major and trace elements on
their pathogenesis: a review.
AB - Kidney stone disease is a polygenic and multifactorial disorder with a worldwide
distribution, and its incidence and prevalence are increasing. Although
significant progress has been made in recent years towards identifying the
specific factors that contribute to the formation of kidney stone, many questions
on the pathogenesis of kidney stones remain partially or completely unanswered.
However, none of the proposed mechanisms specifically consider the role(s) of the
trace elements and, consequently, the contribution of trace constituents to the
pathogenesis of kidney stones remains unclear and under debate. The findings of
some studies seem to support a role for some major and trace elements in the
initiation of stone crystallization, including as a nucleus or nidus for the
formation of the stone or simply as a contaminant of the stone structure. Thus,
the analysis of kidney stones is an important component of investigations on
nephrolithiasis in order to understand the role of trace constituents in the
formation of kidney stones and to formulate future strategies for the treatment
and prevention of stone formation and its recurrence. The aim of this review is
to compare and evaluate the methods/procedures commonly used in the analysis of
urinary calculi. We also highlight the role of major and trace elements in the
pathogenesis of kidney stones.
PMID- 28510036
TI - [Caring for patients-but carefully of course : Structured Handover].
PMID- 28510035
TI - Ketone Bodies as a Possible Adjuvant to Ketogenic Diet in PDHc Deficiency but Not
in GLUT1 Deficiency.
AB - OBJECTIVE: Ketogenic diet is the first line therapy for neurological symptoms
associated with pyruvate dehydrogenase deficiency (PDHD) and intractable seizures
in a number of disorders, including GLUT1 deficiency syndrome (GLUT1-DS). Because
high-fat diet raises serious compliance issues, we investigated if oral L,D-3
hydroxybutyrate administration could be as effective as ketogenic diet in PDHD
and GLUT1-DS. METHODS: We designed a partial or total progressive substitution of
KD with L,D-3-hydroxybutyrate in three GLUT1-DS and two PDHD patients. RESULTS:
In GLUT1-DS patients, we observed clinical deterioration including increased
frequency of seizures and myoclonus. In parallel, ketone bodies in CSF decreased
after introducing 3-hydroxybutyrate. By contrast, two patients with PDHD showed
clinical improvement as dystonic crises and fatigability decreased under basal
metabolic conditions. In one of the two PDHD children, 3-hydroxybutyrate has
largely replaced the ketogenic diet, with the latter that is mostly resumed only
during febrile illness. Positive direct effects on energy metabolism in PDHD
patients were suggested by negative correlation between ketonemia and lactatemia
(r 2 = 0.59). Moreover, in cultured PDHc-deficient fibroblasts, the increase of
CO2 production after 14C-labeled 3-hydroxybutyrate supplementation was consistent
with improved Krebs cycle activity. However, except in one patient, ketonemia
tended to be lower with 3-hydroxybutyrate administration compared to ketogenic
diet. CONCLUSION: 3-hydroxybutyrate may be an adjuvant treatment to ketogenic
diet in PDHD but not in GLUT1-DS under basal metabolic conditions. Nevertheless,
ketogenic diet is still necessary in PDHD patients during febrile illness.
PMID- 28510038
TI - MOLS sampling and its applications in structural biophysics.
AB - This review describes the MOLS method and its applications. This computational
method has been developed in our laboratory primarily to explore the
conformational space of small peptides and identify features of interest,
particularly the minima, i.e., the low energy conformations. A systematic "brute
force" search through the vast conformational space for such features faces the
insurmountable problem of combinatorial explosion, whilst other techniques, e.g.,
Monte Carlo searches, are somewhat limited in their region of exploration and may
be considered inexhaustive. The MOLS method, on the other hand, uses a sampling
technique commonly employed in experimental design theory to identify a small
sample of the conformational space that nevertheless retains information about
the entire space. The information is extracted using a technique that is a
variant of the self-consistent mean field technique, which has been used to
identify, for example, the optimal set of side-chain conformations in a protein.
Applications of the MOLS method to understand peptide structure, predict the
structures of loops in proteins, predict three-dimensional structures of small
proteins, and arrive at the best conformation, orientation, and positions of a
small molecule ligand in a protein receptor site have all yielded satisfactory
results.
PMID- 28510037
TI - Optical imaging of nanoscale cellular structures.
AB - Visualization of subcellular structures and their temporal evolution is of utmost
importance to understand a vast range of biological processes. Optical microscopy
is the method of choice for imaging live cells and tissues; it is minimally
invasive, so processes can be observed over extended periods of time without
generating artifacts due to intense light irradiation. The use of fluorescence
microscopy is advantageous because biomolecules or supramolecular structures of
interest can be labeled specifically with fluorophores, so the images reveal
information on processes involving only the labeled molecules. The key
restriction of optical microscopy is its moderate resolution, which is limited to
about half the wavelength of light (~200 nm) due to fundamental physical laws
governing wave optics. Consequently, molecular processes taking place at spatial
scales between 1 and 100 nm cannot be studied by regular optical microscopy. In
recent years, however, a variety of super-resolution fluorescence microscopy
techniques have been developed that circumvent the resolution limitation. Here,
we present a brief overview of these techniques and their application to cellular
biophysics.
PMID- 28510039
TI - Synaptopodin family of natively unfolded, actin binding proteins: physical
properties and potential biological functions.
AB - The synaptopodin family of proteins consists of at least 3 members: synaptopodin,
the synaptopodin 2 proteins, and the synaptopodin 2-like proteins. Each family
member has at least 3 isoforms that are produced by alternative splicing.
Synaptopodin family members are basic proteins that are rich in proline and have
little regular 2 degrees or 3 degrees structure at physiological temperature,
pH and ionic strength. Like other natively unfolded proteins, synaptopodin family
members have multiple binding partners including actin and other actin-binding
proteins. Several members of the synaptopodin family have been shown to stimulate
actin polymerization and to bundle actin filaments either on their own or in
collaboration with other proteins. Synaptopodin 2 has been shown to accelerate
nucleation of actin filament formation and to induce actin bundling. The actin
polymerization activity is inhibited by Ca2+-calmodulin. Synaptopodin 2 proteins
are localized in Z-bands of striated and heart muscle and dense bodies of smooth
muscle cells. Depending on the developmental status and stress, at least one
member of the synaptopodin family can occupy nuclei of some cells. Members of the
synaptopodin 2 subfamily have been implicated in cancers.
PMID- 28510040
TI - Fibril formation from the amyloid-beta peptide is governed by a dynamic
equilibrium involving association and dissociation of the monomer.
AB - Here I review the molecular mechanisms by which water-soluble monomeric amyloid
beta (Abeta) peptides are transformed into well-organized supramolecular
complexes called amyloid fibrils. The mechanism of amyloid formation is
considered theoretically on the basis of experimental results, and the structural
and mechanistic similarities of amyloid fibrils to three-dimensional crystals are
highlighted. A number of important results from the literature are described.
These include the observation that a correct ratio of monomer association and
dissociation rate constants is key for formation of well-organized amyloid
fibrils. The dynamic nature of the amyloid-beta structure is discussed, along
with the possibly obligate requirement of the transient formation of a hairpin
like fold prior to its incorporation into amyloid fibrils. Many rounds of monomer
association and dissociation events may be present during an apparently silent
lag-period. Amongst these association/dissociation events, interaction between
the C-terminal regions of the Abeta peptide seems to be more favored. Such
association and dissociation events occurring in a "trial-and-error" fashion may
be an important requirement for the formation of well-organized amyloid fibrils.
PMID- 28510042
TI - A career in biophysical chemistry beckons: thoughts on the beginning of a journey
from a young female scientist.
PMID- 28510041
TI - The Keap1-Nrf2 pathway: promising therapeutic target to counteract ROS-mediated
damage in cancers and neurodegenerative diseases.
AB - The overproduction of reactive oxygen species (ROS) generates oxidative stress in
cells. Oxidative stress results in various pathophysiological conditions,
especially cancers and neurodegenerative diseases (NDD). The Keap1-Nrf2 [Kelch
like ECH-associated protein 1-nuclear factor (erythroid-derived 2)-like 2]
regulatory pathway plays a central role in protecting cells against oxidative and
xenobiotic stresses. The Nrf2 transcription factor activates the transcription of
several cytoprotective genes that have been implicated in protection from cancer
and NDD. The Keap1-Nrf2 system acts as a double-edged sword: Nrf2 activity
protects cells and makes the cell resistant to oxidative and electrophilic
stresses, whereas elevated Nrf2 activity helps in cancer cell survival and
proliferation. Several groups in the recent past, from both academics and
industry, have reported the potential role of Nrf2-mediated transcription to
protect from cancer and NDD, resulting from mechanisms involving xenobiotic and
oxidative stress. It suggests that the Keap1-Nrf2 system is a potential
therapeutic target to combat cancer and NDD by designing and developing
modulators (inhibitors/activators) for Nrf2 activation. Herein, we review and
discuss the recent advancement in the regulation of the Keap1-Nrf2 system, its
role under physiological and pathophysiological conditions including cancer and
NDD, and modulators design strategies for Nrf2 activation.
PMID- 28510044
TI - A review and summary of the contents of biophysical reviews volume 8, 2016.
PMID- 28510043
TI - Pseudophosphorylation of cardiac myosin regulatory light chain: a promising new
tool for treatment of cardiomyopathy.
AB - Many genetic mutations in sarcomeric proteins, including the cardiac myosin
regulatory light chain (RLC) encoded by the MYL2 gene, have been implicated in
familial cardiomyopathies. Yet, the molecular mechanisms by which these mutant
proteins regulate cardiac muscle mechanics in health and disease remain poorly
understood. Evidence has been accumulating that RLC phosphorylation has an
influential role in striated muscle contraction and, in addition to the
conventional modulation via Ca2+ binding to troponin C, it can regulate cardiac
muscle function. In this review, we focus on RLC mutations that have been
reported to cause cardiomyopathy phenotypes via compromised RLC phosphorylation
and elaborate on pseudo-phosphorylation rescue mechanisms. This new methodology
has been discussed as an emerging exploratory tool to understand the role of
phosphorylation as well as a genetic modality to prevent/rescue cardiomyopathy
phenotypes. Finally, we summarize structural effects post-phosphorylation, a
phenomenon that leads to an ordered shift in the myosin S1 and RLC conformational
equilibrium between two distinct states.
PMID- 28510045
TI - Electrostatic field effects on membrane domain segregation and on lateral
diffusion.
AB - Natural membranes are organized structures of neutral and charged molecules
bearing dipole moments which generate local non-homogeneous electric fields. When
subjected to such fields, the molecules experience net forces that can modify the
lipid and protein organization, thus modulating cell activities and influencing
(or even dominating) the biological functions. The energetics of electrostatic
interactions in membranes is a long-range effect which can vary over distance
within r-1 to r-3. In the case of a dipole interacting with a plane of dipoles,
e.g. a protein interacting with a lipid domain, the interaction is stronger than
two punctual dipoles and depends on the size of the domain. In this article, we
review several contributions on how electrostatic interactions in the membrane
plane can modulate the phase behavior, surface topography and mechanical
properties in monolayers and bilayers.
PMID- 28510047
TI - A novel spliceosome-mediated trans-splicing can change our view on genome
complexity of the divergent eukaryote Giardia intestinalis.
AB - Although spliceosomal introns are an abundant landmark in eukaryotic genomes, the
nuclear genome of the divergent eukaryote Giardia intestinalis, the causative
agent of giardiasis, has been considered as "intron-poor" with only five
canonical (cis-spliced) introns. However, three research groups (including ours)
have independently reported a novel class of spliceosomal introns in the G.
intestinalis genome. Three protein-coding genes are split into pieces in the G.
intestinalis genome, and each of the partial coding regions was independently
transcribed into polyadenylated premature mRNAs (pre-mRNAs). The two pre-mRNAs
directly interact with each other by an intermolecular-stem structure formed
between their non-coding portions, and are then processed into mature mRNAs by
spliceosome-mediated trans-splicing. Here, we summarize the recently published
works on split introns ("splintrons") in the G. intestinalis genome, and then
provide our speculation on the functional property of the Giardia spliceosomes
based on the putative ratio of splintrons to canonical introns. Finally, we
discuss a scenario for the transition from typical GT-AG boundaries to non
typical AT-AC boundaries in a particular splintron of Giardia.
PMID- 28510046
TI - Luminescent nanodiamonds for biomedical applications.
AB - In recent years, nanodiamonds have emerged from primarily an industrial and
mechanical applications base, to potentially underpinning sophisticated new
technologies in biomedical and quantum science. Nanodiamonds are relatively
inexpensive, biocompatible, easy to surface functionalise and optically stable.
This combination of physical properties are ideally suited to biological
applications, including intracellular labelling and tracking, extracellular drug
delivery and adsorptive detection of bioactive molecules. Here we describe some
of the methods and challenges for processing nanodiamond materials, detection
schemes and some of the leading applications currently under investigation.
PMID- 28510049
TI - Education for fathers about newborn screening and leftover dried blood spots.
AB - The purpose of this research was to assess the impact of an educational
intervention on paternal knowledge, attitudes, and support about newborn
screening (NBS) and dried blood spots (DBS). Participants (n = 147) were
randomized into one of two groups. The results from this study indicated that
video education tools about NBS and DBS is associated with significantly
increased knowledge, support, and satisfaction for both NBS and research use of
DBS and an opt-out consent approach for DBS among fathers.
PMID- 28510048
TI - nNOS regulation of skeletal muscle fatigue and exercise performance.
AB - Neuronal nitric oxide synthases (nNOS) are Ca2+/calmodulin-activated enzymes that
synthesize the gaseous messenger nitric oxide (NO). nNOSMU and the recently
described nNOSbeta, both spliced nNOS isoforms, are important enzymatic sources
of NO in skeletal muscle, a tissue long considered to be a paradigmatic system
for studying NO-dependent redox signaling. nNOS is indispensable for skeletal
muscle integrity and contractile performance, and deregulation of nNOSMU
signaling is a common pathogenic feature of many neuromuscular diseases. Recent
evidence suggests that both nNOSMU and nNOSbeta regulate skeletal muscle size,
strength, and fatigue resistance, making them important players in exercise
performance. nNOSMU acts as an activity sensor and appears to assist skeletal
muscle adaptation to new functional demands, particularly those of endurance
exercise. Prolonged inactivity leads to nNOS-mediated muscle atrophy through a
FoxO-dependent pathway. nNOS also plays a role in modulating exercise performance
in neuromuscular disease. In the mdx mouse model of Duchenne muscular dystrophy,
defective nNOS signaling is thought to restrict contractile capacity of working
muscle in two ways: loss of sarcolemmal nNOSMU causes excessive ischemic damage
while residual cytosolic nNOSMU contributes to hypernitrosylation of the
ryanodine receptor, causing pathogenic Ca2+ leak. This defect in Ca2+ handling
promotes muscle damage, weakness, and fatigue. This review addresses these recent
advances in the understanding of nNOS-dependent redox regulation of skeletal
muscle function and exercise performance under physiological and neuromuscular
disease conditions.
PMID- 28510052
TI - Biophysics to bedside - the transition.
PMID- 28510051
TI - Proteins in binary solvents.
AB - Proteins in living organisms exist in complex aqueous solutions or embedded in
membranes. In solution, proteins are surrounded by a tightly bound hydration
layer, which is more ordered and less mobile than bulk water. As a consequence,
water plays a major role in controlling protein structure stability,
conformational flexibility, dynamics, and functionality, but it also appears that
protein surface regulates the structuring of the surrounding water. The presence
of cosolvents can modify the hydration layer characteristics and then the whole
protein structural and dynamical properties. Because cytoplasm or biological
liquids are complex solutions, the knowledge of the solvation shell
characteristics in mixed solvents should be considered as a crucial step in
describing biological processes at molecular level. This review reports on recent
studies on the structural and thermodynamic properties of model proteins
dissolved in binary solvent mixtures by small-angle neutron scattering (SANS) and
differential scanning microcalorimetry (DSC) techniques. We will show that
contrast variation SANS experiments allow to acquire a direct knowledge of both
protein structure and protein solvation shell (in terms of low-resolution shape
and solvent/cosolvent composition), while DSC experiments provide information on
all the relevant thermodynamic properties. We will focus on two main points.
First, an extended description of the thermodynamic model used to define the
equilibria between water and cosolvent molecules in the protein solvation shell
will be presented. Second, the determination of the peculiar characteristics of
the protein solvation layer, which will be illustrated by considering different
systems. As a conclusion, we will show that the investigation of structure and
thermodynamics of proteins in binary aqueous mixtures is an important way to
understand the role of hydration in protein stability and activity.
PMID- 28510050
TI - A review of multi-domain and flexible molecular chaperones studies by small-angle
X-ray scattering.
AB - Intrinsic flexibility is closely related to protein function, and a plethora of
important regulatory proteins have been found to be flexible, multi-domain or
even intrinsically disordered. On the one hand, understanding such systems
depends on how these proteins behave in solution. On the other, small-angle X-ray
scattering (SAXS) is a technique that fulfills the requirements to study protein
structure and dynamics relatively quickly with few experimental limitations.
Molecular chaperones from Hsp70 and Hsp90 families are multi-domain proteins
containing flexible and/or disordered regions that play central roles in cellular
proteostasis. Here, we review the structure and function of these proteins by
SAXS. Our general approach includes the use of SAXS data to determine size and
shape parameters, as well as protein shape reconstruction and their validation by
using accessory biophysical tools. Some remarkable examples are presented that
exemplify the potential of the SAXS technique. Protein structure can be
determined in solution even at limiting protein concentrations (for example,
human mortalin, a mitochondrial Hsp70 chaperone). The protein organization,
flexibility and function (for example, the J-protein co-chaperones), oligomeric
status, domain organization, and flexibility (for the Hsp90 chaperone and the Hip
and Hep1 co-chaperones) may also be determined. Lastly, the shape, structural
conservation, and protein dynamics (for the Hsp90 chaperone and both p23 and Aha1
co-chaperones) may be studied by SAXS. We believe this review will enhance the
application of the SAXS technique to the study of the molecular chaperones.
PMID- 28510055
TI - Halfway through a 40-year decision: the journey of a medical graduate.
PMID- 28510057
TI - UV-Vis spectroscopy of tyrosine side-groups in studies of protein structure. Part
2: selected applications.
AB - In Part 2 we discuss application of several different types of UV-Vis
spectroscopy, such as normal, difference, and second-derivative UV absorption
spectroscopy, fluorescence spectroscopy, linear and circular dichroism
spectroscopy, and Raman spectroscopy, of the side-chain of tyrosine residues in
different molecular environments. We review the ways these spectroscopies can be
used to probe complex protein structures.
PMID- 28510056
TI - The two sides of a lipid-protein story.
AB - Protein-membrane interactions play essential roles in a variety of cell functions
such as signaling, membrane trafficking, and transport. Membrane-recruited
cytosolic proteins that interact transiently and interfacially with lipid
bilayers perform several of those functions. Experimental techniques capable of
probing changes on the structural dynamics of this weak association are
surprisingly limited. Among such techniques, electron spin resonance (ESR) has
the enormous advantage of providing valuable local information from both membrane
and protein perspectives by using intrinsic paramagnetic probes in
metalloproteins or by attaching nitroxide spin labels to proteins and lipids. In
this review, we discuss the power of ESR to unravel relevant structural and
functional details of lipid-peripheral membrane protein interactions with special
emphasis on local changes of specific regions of the protein and/or the lipids.
First, we show how ESR can be used to investigate the direct interaction between
a protein and a particular lipid, illustrating the case of lipid binding into a
hydrophobic pocket of chlorocatechol 1,2-dioxygenase, a non-heme iron enzyme
responsible for catabolism of aromatic compounds that are industrially released
in the environment. In the second case, we show the effects of GPI-anchored
tissue-nonspecific alkaline phosphatase, a protein that plays a crucial role in
skeletal mineralization, and on the ordering and dynamics of lipid acyl chains.
Then, switching to the protein perspective, we analyze the interaction with model
membranes of the brain fatty acid binding protein, the major actor in the
reversible binding and transport of hydrophobic ligands such as long-chain,
saturated, or unsaturated fatty acids. Finally, we conclude by discussing how
both lipid and protein views can be associated to address a common question
regarding the molecular mechanism by which dihydroorotate dehydrogenase, an
essential enzyme for the de novo synthesis of pyrimidine nucleotides, and how it
fishes out membrane-embedded quinones to perform its function.
PMID- 28510054
TI - Design and development of genetically encoded fluorescent sensors to monitor
intracellular chemical and physical parameters.
AB - Over the past decades many researchers have made major contributions towards the
development of genetically encoded (GE) fluorescent sensors derived from
fluorescent proteins. GE sensors are now used to study biological phenomena by
facilitating the measurement of biochemical behaviors at various scales, ranging
from single molecules to single cells or even whole animals. Here, we review the
historical development of GE fluorescent sensors and report on their current
status. We specifically focus on the development strategies of the GE sensors
used for measuring pH, ion concentrations (e.g., chloride and calcium), redox
indicators, membrane potential, temperature, pressure, and molecular crowding. We
demonstrate that these fluroescent protein-based sensors have a shared history of
concepts and development strategies, and we highlight the most original concepts
used to date. We believe that the understanding and application of these various
concepts will pave the road for the development of future GE sensors and lead to
new breakthroughs in bioimaging.
PMID- 28510058
TI - UV-Vis spectroscopy of tyrosine side-groups in studies of protein structure. Part
1: basic principles and properties of tyrosine chromophore.
AB - Spectroscopic properties of tyrosine residues may be employed in structural
studies of proteins. Here we discuss several different types of UV-Vis
spectroscopy, like normal, difference and second-derivative UV absorption
spectroscopy, fluorescence spectroscopy, linear and circular dichroism
spectroscopy, and Raman spectroscopy, and corresponding optical properties of the
tyrosine chromophore, phenol, which are used to study protein structure.
PMID- 28510059
TI - Deforestation and Carbon Loss in Southwest Amazonia: Impact of Brazil's Revised
Forest Code.
AB - In 2012 Brazil's National Congress altered the country's Forest Code, decreasing
various environmental protections in the set of regulations governing forests.
This suggests consequences in increased deforestation and emissions of greenhouse
gases and in decreased protection of fragile ecosystems. To ascertain the
effects, a simulation was run to the year 2025 for the municipality (county) of
Boca do Acre, Amazonas state, Brazil. A baseline scenario considered historical
behavior (which did not respect the Forest Code), while two scenarios considered
full compliance with the old Forest Code (Law 4771/1965) and the current Code
(Law 12,651/2012) regarding the protection of "areas of permanent preservation"
(APPs) along the edges of watercourses. The models were parameterized from
satellite imagery and simulated using Dinamica-EGO software. Deforestation actors
and processes in the municipality were observed in loco in 2012. Carbon emissions
and loss of forest by 2025 were computed in the three simulation scenarios. There
was a 10% difference in the loss of carbon stock and of forest between the
scenarios with the two versions of the Forest Code. The baseline scenario showed
the highest loss of carbon stocks and the highest increase in annual emissions.
The greatest damage was caused by not protecting wetlands and riparian zones.
PMID- 28510060
TI - The role of protein kinase C-mediated phosphorylation of sarcomeric proteins in
the heart-detrimental or beneficial?
AB - Protein kinase C (PKC) is a family of serine/threonine protein kinases, and
alterations have been found in PKC isoform expression and localization in the
failing heart. These alterations in PKC activation levels influence the PKC
mediated phosphorylation status of cellular target proteins involved in Ca2+
handling and sarcomeric contraction. The differences observed in the effects due
to PKC-mediated phosphorylation may underlie part of the contractile dysfunction
observed in the failing heart. It is therefore important to establish the
beneficial and detrimental effects of this kinase in the healthy and failing
heart. The function of PKC has been studied intensively; however, the complexity
of the regulation of this kinase makes the interpretation of the different
effects difficult. The main focus of this review is the (patho)physiological
impact of phosphorylation of sarcomeric proteins, myosin light chain-2, troponin
I and T, desmin, myosin binding protein-C, and titin by PKC.
PMID- 28510061
TI - Measuring the flow of molecules in cells.
AB - No methods proposed thus far have the capability to measure molecular flow in
live cells at the single molecule level. Here, we review the potentiality of a
newly established method based on the spatial correlation of fluorescence
fluctuations at a pair of points in the sample (pair correlation method). The
pair correlation function (pCF) offers a unique tool to probe the directionality
of intracellular traffic, by measuring the accessibility of the cellular
landscape and its role in determining the diffusive routes adopted by molecules.
The sensitivity of the pCF method toward detection of barriers means that
different structural elements of the cell can be tested in terms of penetrability
and mechanisms of regulation imparted on molecular flow. This has been recently
demonstrated in a series of studies looking at molecular transport inside live
cells. Here, we will review the theory behind detection of barriers to molecular
flow, the rules to interpret pCF data, and relevant applications to intracellular
transport.
PMID- 28510062
TI - Biological applications of second harmonic imaging.
AB - Second Harmonic Generation (SHG) microscopy dates back to 1974, but effective
biological use of the technique has a history of barely 10 years. It is now
widely used to image collagen in many different applications, and is becoming
useful for imaging myosin and some polysaccharides. A separate line on research
has focussed on SHG dyes, which can provide high-speed indication of membrane
potential and are now in use in neurobiology. This review looks at the progress
to date in these different fields.
PMID- 28510063
TI - Structural gymnastics of multifunctional metamorphic proteins.
AB - The classic structure-function paradigm holds that a protein exhibits a single
well-defined native state that gives rise to its biological function.
Nonetheless, over the past few decades, numerous examples of proteins exhibiting
biological function arising from multiple structural states of varying disorder
have been identified. Most recently, several examples of 'metamorphic proteins',
able to interconvert between vastly different native-like topologies under
physiological conditions, have been characterised with multiple functions. In
this review, we look at the concept of protein metamorphosis in relation to the
current understanding of the protein structure-function landscape. Although
structural dynamism observed for metamorphic proteins provides a novel source of
functional versatility, the dynamic nature of the metamorphic proteins generally
makes them difficult to identify and probe using conventional protein structure
determination methods. However, as the existence of metamorphic proteins has now
been established and techniques enabling the analysis of multiple protein
conformers are improving, it is likely that this class will continue to grow in
number.
PMID- 28510065
TI - Biophysical educational experiment: science and goodwill in Latin America and
Africa.
PMID- 28510064
TI - Optical coherence tomography: fundamental principles, instrumental designs and
biomedical applications.
AB - The advances made in the last two decades in interference technologies, optical
instrumentation, catheter technology, optical detectors, speed of data
acquisition and processing as well as light sources have facilitated the
transformation of optical coherence tomography from an optical method used mainly
in research laboratories into a valuable tool applied in various areas of
medicine and health sciences. This review paper highlights the place occupied by
optical coherence tomography in relation to other imaging methods that are used
in medical and life science areas such as ophthalmology, cardiology, dentistry
and gastrointestinal endoscopy. Together with the basic principles that lay
behind the imaging method itself, this review provides a summary of the
functional differences between time-domain, spectral-domain and full-field
optical coherence tomography, a presentation of specific methods for processing
the data acquired by these systems, an introduction to the noise sources that
plague the detected signal and the progress made in optical coherence tomography
catheter technology over the last decade.
PMID- 28510066
TI - The Delta Opioid Receptor in Pain Control.
AB - Nowadays, the delta opioid receptor (DOPr) represents a promising target for the
treatment of chronic pain and emotional disorders. Despite the fact that they
produce limited antinociceptive effects in healthy animals and in most acute pain
models, DOPr agonists have shown efficacy in various chronic pain models. In this
chapter, we review the progresses that have been made over the last decades in
understanding the role played by DOPr in the control of pain. More specifically,
the distribution of DOPr within the central nervous system and along pain
pathways is presented. We also summarize the literature supporting a role for
DOPr in acute, tonic, and chronic pain models, as well as the mechanisms
regulating its activity under specific conditions. Finally, novel compounds that
have make their way to clinical trials are discussed.
PMID- 28510068
TI - New direct dynamic models of protein interactions coupled to photosynthetic
electron transport reactions.
AB - This review covers the methods of computer simulation of protein interactions
taking part in photosynthetic electron transport reactions. A direct
multiparticle simulation method that simulates reactions describing interactions
of ensembles of molecules in the heterogeneous interior of a cell is developed.
In the models, protein molecules move according to the laws of Brownian dynamics,
mutually orient themselves in the electrical field, and form complexes in the 3D
scene. The method allows us to visualize the processes of molecule interactions
and to calculate the rate constants for protein complex formation reactions in
the solution and in the photosynthetic membrane. Three-dimensional multiparticle
computer models for simulating the complex formation kinetics for plastocyanin
with photosystem I and cytochrome bf complex, and ferredoxin with photosystem I
and ferredoxin:NADP+-reductase are considered. Effects of ionic strength are
featured for wild type and mutant proteins. The computer multiparticle models
describe nonmonotonic dependences of complex formation rates on the ionic
strength as the result of long-range electrostatic interactions.
PMID- 28510067
TI - Immunization During Pregnancy: Impact on the Infant.
AB - Maternal immunization has undergone a paradigm shift in recent years, as women
and healthcare providers accept and recognize the benefits of this strategy not
only for the pregnant woman but also for the developing fetus and young infant.
This article reviews the evidence for active immunization during pregnancy, with
an emphasis on perinatal and infant outcomes. Current recommendations for
immunization during pregnancy are presented, with particular focus on the
routinely recommended vaccines during pregnancy: influenza and Tdap (tetanus,
diphtheria, and pertussis). We discuss future research directions, maternal
vaccines in development, and considerations for optimizing and advancing this
underutilized strategy.
PMID- 28510071
TI - Surgical techniques for open fetal repair of myelomeningocele.
AB - The current standard for fetal repair of myelomeningocele is an open exposure of
the gravid uterus with control of the amniotic membranes, and then a multi-layer
closure of the fetal defect. The nature of the surgical repair has evolved and
requires a series of steps that take into account the delicate nature of the
fetal tissues. The individual surgical steps are described including potential
pitfalls.
PMID- 28510070
TI - Sonographic detection of open spina bifida in the first trimester: review of the
literature.
AB - In the beginnings, sonographic diagnosis of open spina bifida (OSB) relied on the
meticulous scanning of the fetal vertebrae for abnormalities but many defects
were missed. After the mid-1980s, however, with the description of the
intracranial findings in the second trimester (the "lemon sign" and the "banana
sign"), the prenatal diagnosis of OSB was enhanced. In the last 2 decades, there
has been widespread uptake of routine ultrasound examination in the first
trimester of pregnancy with the purpose of the measurement of fetal crown-rump
length to determine gestational age, to screen for trisomy 21 and other
aneuploidies, mainly with the nuchal translucency, and for diagnosis of many
major abnormalities. Many papers were published focusing on early diagnosis of
myelomeningocele (MMC), and the objective of this review is to summarize the
different techniques described regarding prenatal diagnosis of OSB in the first
trimester of pregnancy.
PMID- 28510069
TI - Multi-dimensional correlative imaging of subcellular events: combining the
strengths of light and electron microscopy.
AB - To genuinely understand how complex biological structures function, we must
integrate knowledge of their dynamic behavior and of their molecular machinery.
The combined use of light or laser microscopy and electron microscopy has become
increasingly important to our understanding of the structure and function of
cells and tissues at the molecular level. Such a combination of two or more
different microscopy techniques, preferably with different spatial- and temporal
resolution limits, is often referred to as 'correlative microscopy'. Correlative
imaging allows researchers to gain additional novel structure-function
information, and such information provides a greater degree of confidence about
the structures of interest because observations from one method can be compared
to those from the other method(s). This is the strength of correlative (or
'combined') microscopy, especially when it is combined with combinatorial or non
combinatorial labeling approaches. In this topical review, we provide a brief
historical perspective of correlative microscopy and an in-depth overview of
correlative sample-preparation and imaging methods presently available, including
future perspectives on the trend towards integrative microscopy and
microanalysis.
PMID- 28510072
TI - Fetal ventriculomegaly: Diagnosis, treatment, and future directions.
AB - Fetal ventriculomegaly (VM) refers to the enlargement of the cerebral ventricles
in utero. It is associated with the postnatal diagnosis of hydrocephalus. VM is
clinically diagnosed on ultrasound and is defined as an atrial diameter greater
than 10 mm. Because of the anatomic detailed seen with advanced imaging, VM is
often further characterized by fetal magnetic resonance imaging (MRI). Fetal VM
is a heterogeneous condition with various etiologies and a wide range of
neurodevelopmental outcomes. These outcomes are heavily dependent on the presence
or absence of associated anomalies and the direct cause of the ventriculomegaly
rather than on the absolute degree of VM. In this review article, we discuss
diagnosis, work-up, counseling, and management strategies as they relate to fetal
VM. We then describe imaging-based research efforts aimed at using prenatal data
to predict postnatal outcome. Finally, we review the early experience with fetal
therapy such as in utero shunting, as well as the advances in prenatal diagnosis
and fetal surgery that may begin to address the limitations of previous
therapeutic efforts.
PMID- 28510075
TI - Editorial.
PMID- 28510074
TI - Contractility assessment in enzymatically isolated cardiomyocytes.
AB - The use of enzymatically isolated cardiac myocytes is ubiquitous in modern
cardiovascular research. Parallels established between cardiomyocyte shortening
responses and those of intact tissue make the cardiomyocyte an invaluable
experimental model of cardiac function. Much of our understanding regarding the
fundamental processes underlying heart function is owed to our increasing
capabilities in single-cell stimulation and direct or indirect observation, as
well as quantitative analysis of such cells. Of the many important mechanisms and
functions that can be readily assessed in cardiomyocytes at all stages of
development, contractility is the most representative and one of the most
revealing. The purpose of this review is to provide a survey of various
methodological approaches in the literature used to assess adult and neonatal
cardiomyocyte contractility. The various methods employed to evaluate the
contractile behavior of enzymatically isolated mammalian cardiac myocytes can be
conveniently divided into two general categories-those employing optical (image)
based systems and those that use transducer-based technologies. This survey is by
no means complete, but we have made an effort to include the most popular methods
in terms of reliability and accessibility. These techniques are in constant
evolution and hold great promise for the next generation of breakthrough studies
in cell biology for the prevention, treatment, and cure of cardiovascular
diseases.
PMID- 28510076
TI - Application of a systems approach to study developmental gene regulation.
AB - All cells in a multicellular organism contain the same genome, yet different cell
types express different sets of genes. Recent advances in high throughput genomic
technologies have opened up new opportunities to understand the gene regulatory
network in diverse cell types in a genome-wide manner. Here, I discuss recent
advances in experimental and computational approaches for the study of gene
regulation in embryonic development from a systems perspective. This review is
written for computational biologists who have an interest in studying
developmental gene regulation through integrative analysis of gene expression,
chromatin landscape, and signaling pathways. I highlight the utility of publicly
available data and tools, as well as some common analysis approaches.
PMID- 28510073
TI - Modeling of mammalian olfactory receptors and docking of odorants.
AB - Olfactory receptors (ORs) belong to the superfamily of G protein-coupled
receptors (GPCRs), the second largest class of genes after those related to
immunity, and account for about 3 % of mammalian genomes. ORs are present in all
multicellular organisms and represent more than half the GPCRs in mammalian
species (e.g., the mouse OR repertoire contains >1,000 functional genes). ORs are
mainly expressed in the olfactory epithelium where they detect odorant molecules,
but they are also expressed in a number of other cells, such as sperm cells,
although their functions in these cells remain mostly unknown. It has recently
been reported that ORs are present in tumoral tissues where they are expressed at
different levels than in healthy tissues. A specific OR is over-expressed in
prostate cancer cells, and activation of this OR has been shown to inhibit the
proliferation of these cells. Odorant stimulation of some of these receptors
results in inhibition of cell proliferation. Even though their biological role
has not yet been elucidated, these receptors might constitute new targets for
diagnosis and therapeutics. It is important to understand the activation
mechanism of these receptors at the molecular level, in particular to be able to
predict which ligands are likely to activate a particular receptor
('deorphanization') or to design antagonists for a given receptor. In this
review, we describe the in silico methodologies used to model the three
dimensional (3D) structure of ORs (in the more general framework of GPCR
modeling) and to dock ligands into these 3D structures.
PMID- 28510077
TI - Molecular dynamics simulations of membrane proteins.
AB - Membrane proteins control the traffic across cell membranes and thereby play an
essential role in cell function from transport of various solutes to immune
response via molecular recognition. Because it is very difficult to determine the
structures of membrane proteins experimentally, computational methods have been
increasingly used to study their structure and function. Here we focus on two
classes of membrane proteins-ion channels and transporters-which are responsible
for the generation of action potentials in nerves, muscles, and other excitable
cells. We describe how computational methods have been used to construct models
for these proteins and to study the transport mechanism. The main computational
tool is the molecular dynamics (MD) simulation, which can be used for everything
from refinement of protein structures to free energy calculations of transport
processes. We illustrate with specific examples from gramicidin and potassium
channels and aspartate transporters how the function of these membrane proteins
can be investigated using MD simulations.
PMID- 28510079
TI - Conformational flexibility of N-glycans in solution studied by REMD simulations.
AB - Protein-glycan recognition regulates a wide range of biological and pathogenic
processes. Conformational diversity of glycans in solution is apparently
incompatible with specific binding to their receptor proteins. One possibility is
that among the different conformational states of a glycan, only one conformer is
utilized for specific binding to a protein. However, the labile nature of glycans
makes characterizing their conformational states a challenging issue. All-atom
molecular dynamics (MD) simulations provide the atomic details of glycan
structures in solution, but fairly extensive sampling is required for simulating
the transitions between rotameric states. This difficulty limits application of
conventional MD simulations to small fragments like di- and tri-saccharides.
Replica-exchange molecular dynamics (REMD) simulation, with extensive sampling of
structures in solution, provides a valuable way to identify a family of glycan
conformers. This article reviews recent REMD simulations of glycans carried out
by us or other research groups and provides new insights into the conformational
equilibria of N-glycans and their alteration by chemical modification. We also
emphasize the importance of statistical averaging over the multiple conformers of
glycans for comparing simulation results with experimental observables. The
results support the concept of "conformer selection" in protein-glycan
recognition.
PMID- 28510081
TI - QT Prolongation as an Isolated Long-Term Cardiac Manifestation of Dichlorvos
Organophosphate Poisoning in Rats.
AB - Organophosphates (OP) are used extensively as pesticides and as chemical weapons.
Cardiotoxicity is a major concern in survivors of the acute poisoning. To
characterize the delayed cardiac effects of OP, rats were poisoned by
intraperitoneal administration of dichlorvos. In group I, poisoning (0.25-, 0.75
, 1.4-LD50) was followed by application of atropine and obidoxime. In group II,
poisoning (0.35-, 0.5-LD50) was done without antidotes. Cardiac evaluation
included electrocardiography and echocardiography 2- and 6-week post-exposure,
arrhythmia susceptibility following administration of Isoproterenol (150 mcg/kg),
and histological evaluation. All poisoned animals displayed cholinergic symptoms.
In group I, all animals exposed to 1.4-LD50 (n = 3) had profound convulsions and
died despite antidote treatment. However, in the lower doses, all animals
survived and no cardiac abnormalities were noted during follow-up. In group II,
six animals had convulsions and died. Surviving animals had mild but significant
prolongation of corrected QT at both 2 and 6 weeks, compared to shams. There were
no notable echocardiographic, gravimetric, or histological differences between
poisoned and sham animals. Our data indicate that dichlorvos poisoning is
associated with QT prolongation without anatomical or histopathological
abnormalities. This new model can be used to elaborate the molecular mechanism?s
of QT prolongation following OP poisoning.
PMID- 28510078
TI - Assessing and refining molecular dynamics simulations of proteins with nuclear
magnetic resonance data.
AB - The sophistication of the force fields, algorithms and hardware used for
molecular dynamics (MD) simulations of proteins is continuously increasing. No
matter how advanced the methodology, however, it is essential to evaluate the
appropriateness of the structures sampled in a simulation by comparison with
quantitative experimental data. Solution nuclear magnetic resonance (NMR) data
are particularly useful for checking the quality of protein simulations, as they
provide both structural and dynamic information on a variety of temporal and
spatial scales. Here, various features and implications of using NMR data to
validate and bias MD simulations are outlined, including an overview of the
different types of NMR data that report directly on structural properties and of
relevant simulation techniques. The focus throughout is on how to properly
account for conformational averaging, particularly within the context of the
assumptions inherent in the relationships that link NMR data to structural
properties.
PMID- 28510080
TI - Identifying and Prioritizing the Barriers and Facilitators to the Self-Management
of Type 2 Diabetes Mellitus: A Community-Centered Approach.
AB - OBJECTIVE: Self-management of type 2 diabetes mellitus is crucial to controlling
the disease and preventing harm. Multiple factors have been identified in the
literature as potential barriers and facilitators to self-management, but the
magnitude and directionality of these factors are seldom studied. We sought to
develop and test an instrument to identify and quantify the barriers and
facilitators to self-management of type 2 diabetes. METHODS: A community-centered
approach was used to design, implement, and interpret the results of a stated
preference study. All activities were guided by a diverse stakeholder board.
Based on previously reported development work, a novel survey instrument
consisting of 13 potential barriers and facilitators was pretested and piloted in
our local community. Participants were asked to discuss, rate, and rank each
factor. A simple self-explicated method was used to quantify the data and Z
scores were used for hypothesis testing. RESULTS: In total, 25 patients with self
reported type 2 diabetes (64% female; 92% minorities) participated in the pretest
and pilot. Time commitments (Z = -3.72), lack of active support groups (Z =
3.39) and other resources in the local community (Z = -2.96), and
language/culture (Z = -2.69) were identified as barriers to self-management.
Access to healthy food (Z = +5.68), personal understanding (Z = +4.81), and
communication with healthcare providers (Z = +4.62) were identified as
facilitators. CONCLUSION: We demonstrate that factors impacting self-management
can be quantified and categorized as barriers and facilitators. While further
refinement to some factors and investigation into alternative prioritization
methods is necessary, our stakeholder board endorsed moving this to a large
nationally representative study to see how these factors vary across different
people.
PMID- 28510084
TI - Innovations in publication: free sharing of all Biophysical Reviews' content.
PMID- 28510082
TI - Biomedical applications of nanotechnology.
AB - The ability to investigate substances at the molecular level has boosted the
search for materials with outstanding properties for use in medicine. The
application of these novel materials has generated the new research field of
nanobiotechnology, which plays a central role in disease diagnosis, drug design
and delivery, and implants. In this review, we provide an overview of the use of
metallic and metal oxide nanoparticles, carbon-nanotubes, liposomes, and
nanopatterned flat surfaces for specific biomedical applications. The chemical
and physical properties of the surface of these materials allow their use in
diagnosis, biosensing and bioimaging devices, drug delivery systems, and bone
substitute implants. The toxicology of these particles is also discussed in the
light of a new field referred to as nanotoxicology that studies the surface
effects emerging from nanostructured materials.
PMID- 28510086
TI - New insights into real-time multiprotein fluorescence microscopy.
PMID- 28510087
TI - Why we need to stop explaining science.
PMID- 28510085
TI - Cardiac aging and heart disease in humans.
AB - The world population continues to grow older rapidly, mostly because of declining
fertility and increasing longevity. Since age represents the largest risk factor
for cardiovascular disease, the prevalence of these pathologies increases
dramatically with increasing age. In order to improve patient care and prevention
for age-related cardiac diseases, insight should be gained from the analysis of
processes involved in and leading to cardiac aging. It is from this perspective
that we provide here an overview of changes associated with age in the heart on
four levels: functional, structural, cellular and molecular. We highlight those
changes that are in common with the development of the two major age-associated
cardiac pathologies: heart failure and atrial fibrillation. These commonly
affected processes in aging and cardiac pathophysiology may provide an
explanation for the age risk factor in cardiac disease.
PMID- 28510083
TI - Software for molecular docking: a review.
AB - Molecular docking methodology explores the behavior of small molecules in the
binding site of a target protein. As more protein structures are determined
experimentally using X-ray crystallography or nuclear magnetic resonance (NMR)
spectroscopy, molecular docking is increasingly used as a tool in drug discovery.
Docking against homology-modeled targets also becomes possible for proteins whose
structures are not known. With the docking strategies, the druggability of the
compounds and their specificity against a particular target can be calculated for
further lead optimization processes. Molecular docking programs perform a search
algorithm in which the conformation of the ligand is evaluated recursively until
the convergence to the minimum energy is reached. Finally, an affinity scoring
function, DeltaG [U total in kcal/mol], is employed to rank the candidate poses
as the sum of the electrostatic and van der Waals energies. The driving forces
for these specific interactions in biological systems aim toward
complementarities between the shape and electrostatics of the binding site
surfaces and the ligand or substrate.
PMID- 28510088
TI - Seeing the light with BLUF proteins.
AB - First described about 15 years ago, BLUF (Blue Light Using Flavin) domains are
light-triggered switches that control enzyme activity or gene expression in
response to blue light, remaining activated for seconds or even minutes after
stimulation. The conserved, ferredoxin-like fold holds a flavin chromophore that
captures the light and somehow triggers downstream events. BLUF proteins are
found in both prokaryotes and eukaryotes and have a variety of architectures and
oligomeric forms, but the BLUF domain itself seems to have a well-preserved
structure and mechanism that have been the focus of intense study for a number of
years. Crystallographic and NMR structures of BLUF domains have been solved, but
the conflicting models have led to considerable debate about the atomic details
of photo-activation. Advanced spectroscopic and computational methods have been
used to analyse the early events after photon absorption, but these too have led
to widely differing conclusions. New structural models are improving our
understanding of the details of the mechanism and may lead to novel tailor-made
tools for optogenetics.
PMID- 28510091
TI - The emergence of multiple particle tracking in intracellular trafficking of
nanomedicines.
AB - A growing number of nanoparticle systems, termed "nanomedicines", are being
developed for diagnostic and therapeutic applications. Nanoparticles can employ
various cellular entry pathways and trafficking mechanisms to effectively deliver
drugs, biomolecules, and imaging agents to precise sub-cellular locations.
However, the dynamic transport of nanoparticles through the complex intracellular
environment is not well understood, having been primarily studied with static or
bulk averaged methods in the past. Such techniques do not provide detailed
information regarding the transport mechanism and rates of individual
nanoparticles, where understanding of the interaction of nanoparticles with the
cellular environment remains incomplete. Recent advances in live-cell
fluorescence microscopy and real-time multiple particle tracking (MPT) have
facilitated an improved understanding of cell trafficking pathways. Understanding
the dynamic transport of nanoparticles as they are delivered into complex
cellular components may lead to rational improvements in the design of
nanomedicines. This review discusses different cellular uptake and trafficking
pathways of nanomedicines, briefly highlights current fluorescence microscopy
tools, and provides examples from the recent literature on the use of MPT and its
applications.
PMID- 28510092
TI - Protein sorting and membrane-mediated interactions.
AB - Sorting of membrane proteins is of vital importance for living cells. Indeed,
roughly one-third of a eukaryotic cell's proteome consists of peripheral and
transmembrane proteins. These need to be properly distributed and dynamically
maintained at distinct locations in the compartmentalized cell, and one may
wonder how proteins determine where, when, and how to travel to reach a specific
organelle. While specific binary interactions between proteins have been invoked
in explaining the trafficking and sorting processes, a more active role of lipids
in this context has become visible in recent years. In particular, membrane
mediated interactions have been suggested to serve as a robust physicochemical
mechanism to facilitate protein sorting. Here, we will review some recent
insights into these aspects.
PMID- 28510095
TI - The relationship between postmenopausal women's sclerostin levels and their bone
density, age, body mass index, hormonal status, and smoking and consumption of
coffee and dairy products.
PMID- 28510094
TI - The use of biophysical proteomic techniques in advancing our understanding of
diseases.
AB - The use of proteomic approaches in investigating diseases is continuing to expand
and has started to provide answers to substantial gaps in our understanding of
disease pathogenesis as well as in the development of effective strategies for
the early diagnosis and treatment of diseases. Biophysical techniques form a
crucial part of the advanced proteomic techniques currently used and include mass
spectrometry and protein separation techniques, such as two-dimensional gel
electrophoresis and liquid chromatography. The application of biophysical
proteomic techniques in the study of disease includes delineation of altered
protein expression, not only at the whole-cell or tissue levels, but also in
subcellular structures, protein complexes, and biological fluids. These
techniques are also being used for the discovery of novel disease biomarkers,
exploration of the pathogenesis of diseases, development of new diagnostic
methodologies, and identification of new targets for therapeutics. Proteomic
techniques also have the potential for accelerating drug development through more
effective strategies for evaluating a specific drug's therapeutic effects and
toxicity. This article discusses the application of biophysical proteomic
techniques in delineating cardiovascular disease and other diseases, as well as
the limitations and future research directions required for these techniques to
gain greater acceptance and have a larger impact.
PMID- 28510090
TI - The melatonin immunomodulatory actions in radiotherapy.
AB - Radiotherapy has a key role in cancer treatment in more than half of patients
with cancer. The management of severe side effects of this treatment modality is
a limiting factor to appropriate treatment. Immune system responses play a
pivotal role in many of the early and late side effects of radiation. Moreover,
immune cells have a significant role in tumor response to radiotherapy, such as
angiogenesis and tumor growth. Melatonin as a potent antioxidant has shown
appropriate immune regulatory properties that may ameliorate toxicity induced by
radiation in various organs. These effects are mediated through various
modulatory effects of melatonin in different levels of tissue reaction to
ionizing radiation. The effects on the DNA repair system, antioxidant enzymes,
immune cells, cytokines secretion, transcription factors, and protein kinases are
most important. Moreover, anti-cancer properties of melatonin may increase the
therapeutic ratio of radiotherapy. Clinical applications of this agent for the
management of malignancies such as breast cancer have shown promising results. It
seems anti-proliferative, anti-angiogenesis, and stimulation or suppression of
some immune cell responses are the main anti-tumor effects of melatonin that may
help to improve response of the tumor to radiotherapy. In this review, the
effects of melatonin on the modulation of immune responses in both normal and
tumor tissues will be discussed.
PMID- 28510093
TI - Toward a molecular understanding of nanoparticle-protein interactions.
AB - Wherever nanoparticles (NPs) come in contact with a living organism, physical and
chemical interactions take place between the surfaces of the NPs and biomatter,
in particular proteins. When NP are exposed to biological fluids, an adsorption
layer of proteins, a "protein corona" forms around the NPs. Consequently, living
systems interact with the protein-coated NP rather than with a bare NP. To
anticipate biological responses to NPs, we thus require comprehensive knowledge
of the interactions at the bio-nano interface. In recent years, a wide variety of
biophysical techniques have been employed to elucidate mechanistic aspects of NP
protein interactions. In this brief review, we present the latest findings
regarding the composition of the protein corona as it forms on NPs in the blood
stream. We also discuss molecular aspects of this adsorption layer and its time
evolution. The current state of knowledge is summarized, and issues that still
need to be addressed to further advance our understanding of NP-protein
interactions are identified.
PMID- 28510096
TI - Birth weight and its relation with medical nutrition therapy in gestational
diabetes.
AB - PURPOSE: The cornerstone in treatment of gestational diabetes mellitus (GDM) is
medical nutrition therapy (MNT), but the effect on birth weight is disputed. The
birth weight was evaluated with respect to length of MNT and adherence to diet.
METHODS: We performed a cohort study on 436 women with GDM and 254 non-diabetic
women. Women with a normal oral glucose tolerance test were included as controls
as they had similar background predisposition as the women with GDM. The GDM
women were subdivided according to MNT and the nutritional status was further
stratified according to adherence to the current dietary guidelines. RESULTS:
Birth weight above 4 kg was more prevalent in the non-diabetic women compared to
the diet-treated GDM women (27 vs. 18%, p = 0.012) but similar to the GDM women
who had no MNT (24%). Lower birth weight was associated with longer duration of
MNT (r = -0.13, p = 0.021). The birth weight was 1.2 g lower per day of
treatment. CONCLUSIONS: Medical nutrition therapy was associated with reduction
of the fetal weight in women with GDM and the weight decreases with length of
treatment. Birth weight above 4 kg was as prominent in the non-diabetic women as
in the women with GDM without MNT.
PMID- 28510089
TI - Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer,
antimicrobial and immunosuppressive agents.
AB - Photodynamic therapy (PDT) combines a photosensitiser, light and molecular oxygen
to induce oxidative stress that can be used to kill pathogens, cancer cells and
other highly proliferative cells. There is a growing number of clinically
approved photosensitisers and applications of PDT, whose main advantages include
the possibility of selective targeting, localised action and stimulation of the
immune responses. Further improvements and broader use of PDT could be
accomplished by designing new photosensitisers with increased selectivity and
bioavailability. Porphyrin-based photosensitisers with amphiphilic properties,
bearing one or more positive charges, are an effective tool in PDT against
cancers, microbial infections and, most recently, autoimmune skin disorders. The
aim of the review is to present some of the recent examples of the applications
and research that employ this specific group of photosensitisers. Furthermore, we
will highlight the link between their structural characteristics and PDT
efficiency, which will be helpful as guidelines for rational design and
evaluation of new PSs.
PMID- 28510097
TI - AGO Austria recommendation on screening and diagnosis of Lynch syndrome (LS).
AB - PURPOSE: This manuscript reports the consensus recommendations on screening and
diagnosis of Lynch syndrome (LS) in patients with endometrial or ovarian cancer
as well as on possible preventive measures in effectively LS-diagnosed women. The
recommendations are issued by the Austrian Arbeitsgemeinschaft fur Gynakologische
Onkologie (AGO) of the Osterreichischen Gesellschaft fur Gynakologie und
Geburtshilfe (OEGGG) after consultation of the most recent and relevant
literature and following deliberation by the Genetic Task-Force convoked May,
2015 by the AGO Council. RESULTS AND CONCLUSION: The Austrian AGO recommends
immunohistochemical tissue screening for type-I and type-II endometrial cancers
in all patients below the age of 70 years, and for all endometrioid and clear
cell ovarian cancers independently of the patient's age. If needed
immunohistochemistry should be complemented by tissue MLH1 promotor
hypermethylation testing and/or microsatellite instability (MSI) analysis. The
diagnosis LS requires confirmation through identification of a germline mutation
by a molecular genetic examination in the mismatch repair genes using the
patient's blood. This should be performed without preceding tissue screening when
in LS-associated cancer patients the family history fulfills the Amsterdam II or
the revised Bethesda criteria. In LS-diagnosed women, the age for prophylactic
surgery should be set flexibly based on an informed consent. Regarding the
monitoring of these women, chemo-preventive measures as well as screening
procedures either to avoid or to early detect LS-related tumors are discussed
with a special light on their specific limitations.
PMID- 28510100
TI - Liposomal systems as carriers for bioactive compounds.
AB - Since the revolutionary discovery that phospholipids can form closed bilayered
structures in aqueous systems, the study of liposomes has become a very
interesting area of research. The versatility and amazing biocompatibility of
liposomes has resulted in their wide-spread use in many scientific fields, and
many of their applications, especially in medicine, have yielded breakthroughs in
recent decades. Specifically, their easy preparation and various structural
aspects have given rise to broadly usable methodologies to internalize different
compounds, with either lipophilic or hydrophilic properties. The study of
compounds with potential biotechnological application(s) is generally related to
evaluation and risk assessment of the possible cytotoxic or therapeutic effects
of the compound under study. In most cases, undesirable side-effects are
associated with an interaction of the liposome with the cell membrane and/or its
absorption and subsequent interaction with a cellular biomolecule. Liposomal
carrier systems have an unprecedented potential for delivering bioactive
substances to specific molecular targets due to their biocompatibility,
biodegradability and low toxicity. Liposomes are therefore considered to be an
invaluable asset in applied biotechnology studies due to their potential for
interaction with both hydrophilic and lipophilic compounds.
PMID- 28510099
TI - Biophysical chemistry of the ageing eye lens.
AB - This review examines both recent and historical literature related to the
biophysical chemistry of the proteins in the ageing eye, with a particular focus
on cataract development. The lens is a vital component of the eye, acting as an
optical focusing device to form clear images on the retina. The lens maintains
the necessary high transparency and refractive index by expressing crystallin
proteins in high concentration and eliminating all large cellular structures that
may cause light scattering. This has the consequence of eliminating lens fibre
cell metabolism and results in mature lens fibre cells having no mechanism for
protein expression and a complete absence of protein recycling or turnover. As a
result, the crystallins are some of the oldest proteins in the human body. Lack
of protein repair or recycling means the lens tends to accumulate damage with age
in the form of protein post-translational modifications. The crystallins can be
subject to a wide range of age-related changes, including isomerisation,
deamidation and racemisation. Many of these modification are highly correlated
with cataract formation and represent a biochemical mechanism for age-related
blindness.
PMID- 28510098
TI - Body mass index and risk of colorectal carcinoma subtypes classified by tumor
differentiation status.
AB - Previous studies suggest that abnormal energy balance status may dysregulate
intestinal epithelial homeostasis and promote colorectal carcinogenesis, yet
little is known about how host energy balance and obesity influence enterocyte
differentiation during carcinogenesis. We hypothesized that the association
between high body mass index (BMI) and colorectal carcinoma incidence might
differ according to tumor histopathologic differentiation status. Using databases
of the Nurses' Health Study and Health Professionals Follow-up Study, and
duplication-method Cox proportional hazards models, we prospectively examined an
association between BMI and the incidence of colorectal carcinoma subtypes
classified by differentiation features. 120,813 participants were followed for 26
or 32 years and 1528 rectal and colon cancer cases with available tumor
pathological data were documented. The association between BMI and colorectal
cancer risk significantly differed depending on the presence or absence of poorly
differentiated foci (Pheterogeneity = 0.006). Higher BMI was associated with a
higher risk of colorectal carcinoma without poorly-differentiated foci (>=30.0
vs. 18.5-22.4 kg/m2: multivariable-adjusted hazard ratio, 1.87; 95% confidence
interval, 1.49-2.34; Ptrend < 0.001), but not with risk of carcinoma with poorly
differentiated foci (Ptrend = 0.56). This differential association appeared to be
consistent in strata of tumor microsatellite instability or FASN expression
status, although the statistical power was limited. The association between BMI
and colorectal carcinoma risk did not significantly differ by overall tumor
differentiation, mucinous differentiation, or signet ring cell component
(Pheterogeneity > 0.03, with the adjusted alpha of 0.01). High BMI was associated
with risk of colorectal cancer subtype containing no poorly-differentiated focus.
Our findings suggest that carcinogenic influence of excess energy balance might
be stronger for tumors that retain better intestinal differentiation throughout
the tumor areas.
PMID- 28510101
TI - A critical analysis of cancer biobank practices in relation to biospecimen
quality.
AB - There are concerns that a substantial proportion of published research data is
not reproducible, which may partially explain the frequent failure to translate
pre-clinical results to clinical care. High-quality cancer biospecimens are
needed for robust, reproducible research findings, with most researchers
obtaining these specimens from cancer biobanks or tumour banks. This review
provides an overview of the types of quality control (QC) activities conducted
within cancer biobanks that pertain to biospecimen quality and of biospecimen
quality reporting tools, including SPREC and BRISQ. We examine how QC assay
results and other biospecimen data are communicated from biobanks to researchers,
and whether these activities lead to improved biospecimen quality reporting
within the literature and/or to improved research outcomes. We also discuss
operational factors that limit QC activities within biobanks and evidence gaps
requiring further research. In summary, whereas the provision of quality
biospecimens is a common aim of cancer biobanks, QC activities remain
underreported and are rarely discussed in the literature, compared with other
aspects of biobank operations. Further research is required to determine how
biobanks can most efficiently optimise biospecimen quality, and how communication
between biobanks and researchers can be improved.
PMID- 28510102
TI - Natural isoquinoline alkaloids: binding aspects to functional proteins, serum
albumins, hemoglobin, and lysozyme.
AB - The putative anticancer alkaloids berberine, palmatine, jatrorrhizine, and
sanguinarine are known to bind to nucleic acids. To develop them as potential
drugs for therapeutic use, their binding affinity to functional proteins and mode
of transport in the circulatory system need to be clearly understood. Towards
this, many studies on their binding aspects to proteins have been reported and a
considerable amount of data, mostly of biophysical nature, exists in the
literature. The importance of these natural isoquinoline alkaloids and the recent
literature on their interaction phenomena with functional proteins, serum
albumins, hemoglobin, and lysozyme are presented in this review.
PMID- 28510103
TI - Optically-controlled platforms for transfection and single- and sub-cellular
surgery.
AB - Improving the resolution of biological research to the single-cell or sub
cellular level is of critical importance in a wide variety of processes and
disease conditions. Most obvious are those linked to aging and cancer, many of
which are dependent upon stochastic processes where individual, unpredictable
failures or mutations in individual cells can lead to serious downstream
conditions across the whole organism. The traditional tools of biochemistry
struggle to observe such processes: the vast majority are based upon ensemble
approaches analysing the properties of bulk populations, which means that details
of individual constituents is lost. What are required, then, are tools with the
precision and resolution to probe and dissect cells at the single-micron scale:
the scale of the individual organelles and structures that control their
function. In this review, we highlight the use of highly-focused laser beams to
create systems which provide precise control and specificity at the single-cell
or even single-micron level. The intense focal points generated can directly
interact with cells and cell membranes, which in conjunction with related
modalities such as optical trapping provide a broad platform for the development
of single-cell and sub-cellular surgery approaches. These highly tuneable tools
have been demonstrated to deliver or remove material from cells of interest, and
they can simultaneously excite fluorescent probes for imaging purposes or
plasmonic structures for very local heating. We discuss both the history and
recent applications of the field, highlighting the key findings and developments
over the last 40 years of biophotonics research.
PMID- 28510105
TI - Agrochemical loading in drains and rivers and its connection with pollution in
coastal lagoons of the Mexican Pacific.
AB - The state of Sinaloa in Mexico is an industrialized agricultural region with a
documented pesticide usage of 700 t year-1; which at least 17 of the pesticides
are classified as moderately to highly toxic. Pollutants in the water column of
rivers and drains are of great concern because the water flows into coastal
lagoons and nearshore waters and thereby affects aquatic organisms. This study
was done in four municipalities in the state of Sinaloa that produce food
intensively. To investigate the link between pollution in the lagoons and their
proximity to agricultural sites, water was sampled in three coastal lagoons and
in the rivers and drains that flow into them. Seawater from the Gulf of
California, 10 km from the coast, was also analyzed. Concentrations of nutrients,
organochlorines, and organophosphorus pesticides were determined. Nutrient
determination showed an unhealthy environment with N/P ratios of <16, thus
favoring nitrogen-fixing cyanobacteria. The organochlorine pesticides showed a
clear accumulation in the coastal lagoons from the drains and rivers, with
SigmaHCH showing the highest concentrations. In the southern part of the region
studied, pollution of the coastal lagoon of Pabellones could be traced mainly to
the drains from the agricultural sites. Accumulation of OC pesticides was also
observed in the Gulf of California. Tests for 22 organophosphates revealed only
five (diazinon, disulfoton, methyl parathion, chlorpyrifos, and mevinphos);
diazinon was detected at all the sites, although methyl parathion was present at
some sites at concentrations one order of magnitude higher than diazinon.
PMID- 28510106
TI - The pollution characteristics of PM2.5 and correlation analysis with
meteorological parameters in Xinxiang during the Shanghai Cooperation
Organization Prime Ministers' Meeting.
AB - The pollution characteristics of PM2.5 and correlation analysis with
meteorological parameters in Xinxiang during the Shanghai Cooperation
Organization Prime Ministers' Meeting were investigated. During the whole
meeting, nine PM2.5 samples were collected at a suburban site of Xinxiang, and
the average concentration of PM2.5 was 122.28 MUg m-3. NO3-, NH4+, SO42-
accounted for 56.8% of the total water-soluble ions. In addition, with an
exception of Cl-, all of water-soluble ions decreased during the meeting. Total
concentrations of crustal elements ranged from 6.53 to 185.86 MUg m-3, with an
average concentration of 52.51 MUg m-3, which accounted for 82.5% of total
elements. The concentrations of organic carbon and elemental carbon were 7.71 and
1.52 MUg m-3, respectively, lower than those before and after the meeting. It is
indicated that during the meeting, limiting motor vehicles is to reduce exhaust
emissions, delay heating is to reduce the fossil fuel combustion, and other
measures are to reduce the concentration of PM2.5. The directly dispersing by
mixing layer height increase and the indirectly reducing the formation of
secondary aerosol by low relative humidity, and these are the only two key
removing mechanisms of PM2.5 in Xinxiang during the meeting.
PMID- 28510107
TI - Allosteric movements in eubacterial RecA.
AB - The action of RecA, an important eubacterial protein involved in recombination
and repair, involves the transition from an inactive filament in the absence of
DNA to an active filament formed in association with DNA and ATP. The structure
of the inactive filament was first established in Escherichia coli RecA (EcRecA).
The interaction of RecA with non-hydrolysable ATP analogues and ADP has been
thoroughly characterized and the DNA binding loops visualized based on the
crystal structures of the RecA proteins from Mycobacterium tuberculosis (MtRecA)
and Mycobacterium smegmatis (MsRecA). A switch residue, which triggers the
transformation of the information on ATP binding to the DNA binding regions, has
been identified. The 20-residue C-terminal stretch of RecA, which is disordered
in all other relevant crystal structures, has been defined in an MsRecA-dATP
complex. The ordering of the stretch is accompanied by the generation of a new
nucleotide binding site which can communicate with the original nucleotide
binding site of an adjacent molecule in the filament. The plasticity of MsRecA
and its mutants involving the switch residue has been explored by studying
crystals grown under different conditions at two different temperatures and, in
one instance, at low humidity. The structures of these crystals and those of
EcRecA and Deinococcus radiodurans RecA (DrRecA) provide information on
correlated movements involving different regions of the molecule. These
correlated movements appear to be important in the allosteric transitions of RecA
during its action.
PMID- 28510109
TI - A new theoretical approach to biological self-assembly.
AB - Upon biological self-assembly, the number of accessible translational
configurations of water in the system increases considerably, leading to a large
gain in water entropy. It is important to calculate the solvation entropy of a
biomolecule with a prescribed structure by accounting for the change in water
water correlations caused by solute insertion. Modeling water as a dielectric
continuum is not capable of capturing the physical essence of the water entropy
effect. As a reliable tool, we propose a hybrid of the angle-dependent integral
equation theory combined with a multipolar water model and a morphometric
approach. Using our methods wherein the water entropy effect is treated as the
key factor, we can elucidate a variety of processes such as protein folding,
cold, pressure, and heat denaturating of a protein, molecular recognition,
ordered association of proteins such as amyloid fibril formation, and functioning
of ATP-driven proteins.
PMID- 28510108
TI - Application and use of differential scanning calorimetry in studies of thermal
fluctuation associated with amyloid fibril formation.
AB - The aggregation of proteins into amyloid fibrils is a topic that has attracted
great interest because the process is associated with the pathology of numerous
human diseases. Despite considerable progress in the elucidation of the structure
of amyloid fibrils and the kinetic mechanism of their formation, knowledge on the
thermodynamic aspects underlying the formation and stability of amyloid fibrils
is limited. In this review, we summarize recent calorimetric studies of amyloid
fibril formation, with the goal of obtaining a better understanding of the causal
factors that thermally induce proteins to aggregate into amyloid fibrils.
Calorimetric data show that differential scanning calorimetry is a useful
technique to study the causative factors that thermally trigger the conversion to
the amyloid structure and highlight the physics related to the thermal
fluctuation of proteins during this conversion.
PMID- 28510110
TI - Principles of multiparametric optimization for phospholipidomics by 31P NMR
spectroscopy.
AB - Phospholipids have long been known to be the principal constituents of the
bilayer matrix of cell membranes. While the main function of cell membranes is to
provide physical separation between intracellular and extracellular compartments,
further biological and biochemical functions for phospholipids have been
identified more recently, notably in cell signaling, cell recognition and cell
cell interaction, but also in cell growth, electrical insulation of neurons and
many other processes. Therefore, accurate and efficient determination of tissue
phospholipid composition is essential for our understanding of biological tissue
function. 31P NMR spectroscopy is a quantitative and fast method for analyzing
phospholipid extracts from biological samples without prior separation. However,
the number of phospholipid classes and subclasses that can be quantified
separately and reliably in 31P NMR spectra of tissue extracts is critically
dependent on a variety of experimental conditions. Until recently, little
attention has been paid to the optimization of phospholipid 31P NMR spectra. This
review surveys the basic physicochemical properties that determine the quality of
phospholipid spectra, and describes an optimization strategy based on this
assessment. Notably, the following experimental parameters need to be controlled
for systematic optimization: (1) extract concentration, (2) concentration of
chelating agent, (3) pH value of the aqueous component of the solvent system, and
(4) temperature of the NMR measurement. We conclude that a multiparametric
optimization approach is crucial to obtaining highly predictable and reproducible
31P NMR spectra of phospholipids.
PMID- 28510104
TI - Historical perspective on heart function: the Frank-Starling Law.
AB - More than a century of research on the Frank-Starling Law has significantly
advanced our knowledge about the working heart. The Frank-Starling Law mandates
that the heart is able to match cardiac ejection to the dynamic changes occurring
in ventricular filling and thereby regulates ventricular contraction and
ejection. Significant efforts have been attempted to identify a common
fundamental basis for the Frank-Starling heart and, although a unifying idea has
still to come forth, there is mounting evidence of a direct relationship between
length changes in individual constituents (cardiomyocytes) and their sensitivity
to Ca2+ ions. As the Frank-Starling Law is a vital event for the healthy heart,
it is of utmost importance to understand its mechanical basis in order to
optimize and organize therapeutic strategies to rescue the failing human heart.
The present review is a historic perspective on cardiac muscle function. We
"revive" a century of scientific research on the heart's fundamental protein
constituents (contractile proteins), to their assemblies in the muscle (the
sarcomeres), culminating in a thorough overview of the several synergistically
events that compose the Frank-Starling mechanism. It is the authors' personal
beliefs that much can be gained by understanding the Frank-Starling relationship
at the cellular and whole organ level, so that we can finally, in this century,
tackle the pathophysiologic mechanisms underlying heart failure.
PMID- 28510111
TI - Toward a molecular understanding of the photosensitizer-copper interaction for
tumor destruction.
AB - The aim of this study was to shown that the photosensitizer in photodynamic
therapy (PDT) can contribute to the dark toxicity and phototoxicity of the tumor
by binding with copper. This binding process can remove the copper from the body,
stopping angiogenesis as well as activating the mechanisms of cell death, such as
apoptosis and necrosis. In PDT, this coupling may be considered a new route for
fighting cancer in addition to those already known which involve reactive oxygen
species.
PMID- 28510112
TI - Application of advanced fluorescence microscopy to the structure of meiotic
chromosomes.
AB - Chromosomes undergoing meiosis are defined by a macromolecular protein assembly
called the synaptonemal complex which holds homologs together and carries out
important meiotic functions. By retaining the molecular specificity, multiplexing
ability, and in situ imaging capabilities of fluorescence microscopy, but with
vastly increased resolution, 3D-SIM and other superresolution techniques are
poised to make significant discoveries about the structure and function of the
synaptonemal complex. This review discusses recent developments in this field and
poses questions approachable with current and future technology.
PMID- 28510113
TI - Stochastic chemical kinetics : A review of the modelling and simulation
approaches.
AB - A review of the physical principles that are the ground of the stochastic
formulation of chemical kinetics is presented along with a survey of the
algorithms currently used to simulate it. This review covers the main literature
of the last decade and focuses on the mathematical models describing the
characteristics and the behavior of systems of chemical reactions at the nano-
and micro-scale. Advantages and limitations of the models are also discussed in
the light of the more and more frequent use of these models and algorithms in
modeling and simulating biochemical and even biological processes.
PMID- 28510115
TI - Application of Decellularized Tissue Scaffolds in Ovarian Tissue Transplantation.
AB - In tissue engineering, decellularized scaffolds have been proved to have
remarkable capacity to promote regeneration in various organs such as kidney,
heart, lung, and liver. Marrying the field of cryobiology and reproductive
medicine resulted in considerable progress and breakthroughs, which led to the
emergence of ovarian tissue cryopreservation and transplantation as a promising
option for fertility preservation. Here we describe an innovative application of
decellularized tissue scaffolds as a regenerative platform for reconstruction of
ovarian grafts for auto-transplantation.
PMID- 28510114
TI - Fabricating poly(1,8-octanediol citrate) elastomer based fibrous mats via
electrospinning for soft tissue engineering scaffold.
AB - Poly(1,8-octanediol citrate) (POC) is a recently developed biodegradable
crosslinked elastomer that possesses good cytocompatibility and matchable
mechanical properties to soft tissues. However, the thermosetting characteristic
reveals a big challenge to manufacture its porous scaffold. Herein, POC elastomer
was electrospun into fiber mat using poly(L-lactic acid) (PLLA) as a spinnable
carrier. The obtained POC/PLLA fiber mats were characterized by scanning electron
microscopy (SEM), dynamic mechanical analysis (DMA), uniaxial tensile test,
static-water-contact-angle, thermal analysis, in vitro degradation and
biocompatibility test. It was found that the fibrous structure could be formed so
long as the POC pre-polymer's content was no more than 50 wt%. The presence of
elastic POC component not only strengthened the fiber mats but also toughened the
fiber mats. The hydrophilicity of 50/50 fiber mat significantly improved. In
vitro degradation rate of POC based fiber mats was much faster than that of pure
PLLA. Cyto- and histo-compatibility tests confirmed that the POC/PLLA fiber mats
had good biocompatibility for potential applications in soft tissue engineering.
PMID- 28510117
TI - Novex-3, the tiny titin of muscle.
AB - The giant multi-functional striated muscle protein titin is the third most
abundant muscle protein after myosin and actin. Titin plays a pivotal role in
myocardial passive stiffness, structural integrity and stress-initiated signaling
pathways. The complete sequence of the human titin gene contains three isoform
specific mutually exclusive exons [termed novel exons (novex)] coding for the I
band sequence, named novex-1 (exon 45), novex-2 (exon 46) and novex-3 (exon 48).
Transcripts containing either the novex-1 or novex-2 exons code for the novex-1
and novex-2 titin isoforms. The novex-3 transcript contains a stop codon and
polyA tail signal, resulting in an unusually small (~700 kDa) isoform, referred
to as novex-3 titin. This 'tiny titin' isoform extends from the Z-disc (N
terminus) to novex-3 (C-terminus) and is expressed in all striated muscles.
Biochemical analysis of novex-3 titin in cardiomyocytes shows that obscurin, a
vertebrate muscle protein, binds to novex-3 titin. The novex-3/obscurin complex
localizes to the Z-disc region and may regulate calcium, and SH3- and GTPase
associated myofibrillar signaling pathways. Therefore, novex-3 titin could be
involved in stress-initiated sarcomeric restructuring.
PMID- 28510116
TI - Obscure functions: the location-function relationship of obscurins.
AB - The obscurin family of polypeptides is essential for normal striated muscle
function and contributes to the pathogenesis of fatal diseases, including
cardiomyopathies and cancers. The single mammalian obscurin gene, OBSCN, gives
rise to giant (~800 kDa) and smaller (~40-500 kDa) proteins that are composed of
tandem adhesion and signaling motifs. Mammalian obscurin proteins are expressed
in a variety of cell types, including striated muscles, and localize to distinct
subcellular compartments where they contribute to diverse cellular processes.
Obscurin homologs in Caenorhabditis elegans and Drosophila possess a similar
domain architecture and are also expressed in striated muscles. The long sought
after question, "what does obscurin do?" is complex and cannot be addressed
without taking into consideration the subcellular distribution of these proteins
and local isoform concentration. Herein, we present an overview of the functions
of obscurins and begin to define the intricate relationship between their
subcellular distributions and functions in striated muscles.
PMID- 28510120
TI - Obscurin variants and inherited cardiomyopathies.
AB - The inherited cardiomyopathies, hypertrophic cardiomyopathy (HCM), dilated
cardiomyopathy (DCM) and left ventricular non-compaction (LVNC), have been
frequently associated with mutations in sarcomeric proteins. In recent years,
advances in DNA sequencing technology has allowed the study of the giant proteins
of the sarcomere, such as titin and nebulin. Obscurin has been somewhat neglected
in these studies, largely because its functional role is far from clear, although
there was an isolated report in 2007 of obscurin mutations associated with HCM.
Recently, whole exome sequencing methodology (WES) has been used to address
mutations in OBSCN, the gene for obscurin, and OBSCN variants were found to be
relatively common in inherited cardiomyopathies. In different studies, 5 OBSCN
unique variants have been found in a group of 30 end-stage failing hearts, 6
OBSCN unique variants in 74 HCM cases and 3 OBSCN unique variants in 10 LVNC
patients. As yet, the number of known potentially disease-causing OBSCN variants
is quite small. The reason for this is that mutations in the OBSCN gene have not
been recognised as potentially disease-causing until recently, and were not
included in large-scale genetic surveys. OBSCN mutations may be causative of HCM,
DCM and LVNC and other cardiomyopathies, or they may work in concert with other
variants in the same or other genes to initiate the pathology. Currently, the
function of obscurin is not well understood, but we anticipate that many more
OBSCN variants linked to cardiomyopathy will be found when the large cohorts of
patient sequences available are tested. It is to be hoped that the establishment
of the importance of obscurin in pathology will stimulate a thorough
investigation of obscurin function.
PMID- 28510118
TI - Tampering with springs: phosphorylation of titin affecting the mechanical
function of cardiomyocytes.
AB - Reversible post-translational modifications of various cardiac proteins regulate
the mechanical properties of the cardiomyocytes and thus modulate the contractile
performance of the heart. The giant protein titin forms a continuous filament
network in the sarcomeres of striated muscle cells, where it determines passive
tension development and modulates active contraction. These mechanical properties
of titin are altered through post-translational modifications, particularly
phosphorylation. Titin contains hundreds of potential phosphorylation sites, the
functional relevance of which is only beginning to emerge. Here, we provide a
state-of-the-art summary of the phosphorylation sites in titin, with a particular
focus on the elastic titin spring segment. We discuss how phosphorylation at
specific amino acids can reduce or increase the stretch-induced spring force of
titin, depending on where the spring region is phosphorylated. We also review
which protein kinases phosphorylate titin and how this phosphorylation affects
titin-based passive tension in cardiomyocytes. A comprehensive overview is
provided of studies that have measured altered titin phosphorylation and titin
based passive tension in myocardial samples from human heart failure patients and
animal models of heart disease. As our understanding of the broader implications
of phosphorylation in titin progresses, this knowledge could be used to design
targeted interventions aimed at reducing pathologically increased titin stiffness
in patients with stiff hearts.
PMID- 28510121
TI - Can glypican-3 be a disease-specific biomarker?
AB - BACKGROUND: Glypican-3 (GPC3) is a cell surface-bound proteoglycan which has been
identified as a potential biomarker candidate in hepatocellular carcinoma, lung
carcinoma, severe pneumonia, and acute respiratory distress syndrome (ARDS). The
aim of our review is to evaluate whether GPC3 has utility as a disease-specific
biomarker, to discuss the potential involvement of GPC3 in cell biology, and to
consider the changes of GPC3 gene and protein expression and regulation in
hepatocellular carcinoma, lung cancer, severe pneumonia, and ARDS. RESULTS:
Immunohistochemical studies have suggested that over-expression of GPC3 is
associated with a poorer prognosis for hepatocellular carcinoma patients.
Expression of GPC3 leads to an increased apoptosis response in human lung
carcinoma tumor cells, and is considered to be a candidate lung tumor suppressor
gene. Increased serum levels of GPC3 have been demonstrated in ARDS patients with
severe pneumonia. CONCLUSIONS: Glypican-3 could be considered as a clinically
useful biomarker in hepatocellular carcinoma, lung carcinoma, and ARDS, but
further research is needed to confirm and expand on these findings.
PMID- 28510119
TI - Genetic epidemiology of titin-truncating variants in the etiology of dilated
cardiomyopathy.
AB - Heart failure (HF) is a complex clinical syndrome defined by the inability of the
heart to pump enough blood to meet the body's metabolic demands. Major causes of
HF are cardiomyopathies (diseases of the myocardium associated with mechanical
and/or electrical dysfunction), among which the most common form is dilated
cardiomyopathy (DCM). DCM is defined by ventricular chamber enlargement and
systolic dysfunction with normal left ventricular wall thickness, which leads to
progressive HF. Over 60 genes are linked to the etiology of DCM. Titin (TTN) is
the largest known protein in biology, spanning half the cardiac sarcomere and, as
such, is a basic structural and functional unit of striated muscles. It is
essential for heart development as well as mechanical and regulatory functions of
the sarcomere. Next-generation sequencing (NGS) in clinical DCM cohorts
implicated truncating variants in titin (TTNtv) as major disease alleles,
accounting for more than 25% of familial DCM cases, but these variants have also
been identified in 2-3% of the general population, where these TTNtv blur
diagnostic and clinical utility. Taking into account the published TTNtv and
their association to DCM, it becomes clear that TTNtv harm the heart with
position-dependent occurrence, being more harmful when present in the A-band TTN,
presumably with dominant negative/gain-of-function mechanisms. However, these
insights are challenged by the depiction of position-independent toxicity of
TTNtv acting via haploinsufficient alleles, which are sufficient to induce
cardiac pathology upon stress. In the current review, we provide an overview of
TTN and discuss studies investigating various TTN mutations. We also present an
overview of different mechanisms postulated or experimentally validated in the
pathogenicity of TTNtv. DCM-causing genes are also discussed with respect to non
truncating mutations in the etiology of DCM. One way of understanding pathogenic
variants is probably to understand the context in which they may or may not
affect protein-protein interactions, changes in cell signaling, and substrate
specificity. In this regard, we also provide a brief overview of TTN interactions
in situ. Quantitative models in the risk assessment of TTNtv are also discussed.
In summary, we highlight the importance of gene-environment interactions in the
etiology of DCM and further mechanistic studies used to delineate the pathways
which could be targeted in the management of DCM.
PMID- 28510122
TI - Anti-thyroglobulin antibodies do not significantly increase the risk of finding
iodine avid metastases on post-radioactive iodine ablation scan in low-risk
thyroid cancer patients.
AB - OBJECTIVE: Post-operative thyroglobulin (Tg) levels can predict the likelihood of
residual cancer, including distant metastases, thereby influencing postsurgical
treatment strategies even in patients with low-risk disease. Circulating anti
thyroglobulin antibodies (anti-Tg Abs) interfere with Tg measurement preventing
this clinical use. It is not known if the presence of anti-Tg Abs predicts
metastatic disease on post-therapy scan in patients with low-risk disease or if
they should influence the use or dose of I-131 therapy. In the present study, we
compare post-therapy scans in low-risk patients with and without anti-Tg Abs.
METHODS: This is a single-institution retrospective study. The study population
(Group A) included all patients with low-risk differentiated thyroid cancer (DTC)
who underwent total thyroidectomy and RAI between 1/1/2006 to 9/11/2015 with
intrathyroidal T1-T2, Nx, N0 or N1a (<=5 nodes all measuring, when reported, <2
mm) that had anti-thyroglobulin antibodies. Patients were excluded if they had
known distant metastases and/or extensive vascular invasion. A second group of
patients (Group B) treated during the same period but without anti-Tg antibodies
was selected to match group A by propensity core matching with a logistic
regression model. RESULTS: Each group included 37 patients. In group A: Median
age was 40 years, 86% female and 76% PTC. Median tumor size was 2 cm (0.2-3.8),
32% had multifocal disease, 16% were N1a and 4% had vascular invasion. Parameters
in group B were not statistically different from Group A, as expected based on
the selection criteria, except being less likely to have Hashimoto's thyroiditis
on pathology (p < 0.001). Post-therapy scan results were compared by Chi-square
test with 86% negative post therapy scan frequency in group A and 92% in group B
without evidence of a difference (p = 0.45). CONCLUSION: In patients with low
risk DTC, anti-Tg Abs did not significantly predict metastatic disease on post
therapy scan. If confirmed, these data suggest that the presence of anti-Tg Abs
alone should not influence initial therapy in patients with low-risk DTC.
PMID- 28510123
TI - Alzheimer's disease Abeta42 peptide induces an increase in Na,K-ATPase
glutathionylation.
AB - We have shown that the inhibition of Na,K-ATPase during its long-term incubation
with amyloid beta (Abeta42), an Alzheimer's disease protein, is caused by the
change in the thiol redox status of cells leading to induction of
glutathionylation alpha-subunit of Na,K-ATPase. To restore the activity of Na,K
ATPase, it is proposed to use reducing agents, which promote normalization of the
redox status of cells and deglutathionylation of the protein.
PMID- 28510124
TI - Computer-aided estimation of the hERG-mediated cardiotoxicity risk of potential
drug components.
AB - The hERG potassium channel is one of the most important anti-targets determining
cardiotoxicity of potential drugs. Using fragmental descriptors and artificial
neural networks, the predictive models of the relationship between the structure
of organic compounds and their activity with respect to hERG were built, and the
structural factors affecting it were analyzed. By their predictive ability and
applicability domain, these models (N = 1000, Q 2 = 0.77, RMSE cv = 0.45 for
affinity and N = 2886, Q 2 = 0.60, RMSE cv = 0.55 for channel inhibition) are
superior to the previously published models and can be used to minimize the risk
of cardiotoxicity during drug development.
PMID- 28510125
TI - Molecular design of proneurogenic and neuroprotective compounds-allosteric NMDA
receptor modulators.
AB - N-Methyl-D-aspartic acid (NMDA) receptor is a promising target for treatment of
neurodegenerative diseases and other brain disorders as well as for designing
proneurogenic compounds able to stimulate neurogenesis in adult brain. We
analyzed the structure of the binding site of negative allosteric modulators in
the amino-terminal domain of the NMDA receptor and identified possible modes of
their binding as well as performed molecular design of new modulators that
significantly differ from the known ones in structure and binding mode. In
addition, we formed a focused library of chemical compounds with potential
neuroprotective and proneurogenic properties, desirable set of pharmacokinetic
properties, and low toxicity, which can be the basis for development of new
generation drugs.
PMID- 28510126
TI - Dehydrin stress proteins in Pinus sylvestris L. needles under conditions of
extreme climate of Yakutia.
AB - This is the first study to investigate stress proteins dehydrins with the use of
specific antibodies in the Scots pine (Pinus sylvestris L.) needles and their
changes in the annual cycle under extreme climate of Yakutia. No pronounced
polymorphism of major dehydrins (14-15 and 66 kDa) has been found during the
winter dormancy period of P. sylvestris. A clear correlation between the seasonal
variations in dehydrins and changes in the water content in needles was revealed.
Consistently high levels of dehydrins was retained throughout the period of low
negative temperatures. It is assumed that dehydrins can participate in the
formation of P. sylvestris L. resistance to the permafrost conditions.
PMID- 28510127
TI - Negative-sense virion RNA of segment 8 (NS) of influenza a virus is able to
translate in vitro a new viral protein.
AB - It was shown that full-length virion RNA of segment 8 of influenza virus
A/Aichi/2/68 (H3N2) can initiate the synthesis of two major polypeptides with
molecular weights of 23 and 13 kD and a minor polypeptide with a molecular weight
of 19 kDa, which specifically reacted with the antibodies to the 30-membered
peptide of the central part of the NSP protein of influenza A virus. Thus, the
genomic-polarity RNA of segment 8 of influenza virus A has a translational
template function. These data provide further confirmation of the concept of the
bipolar (ambisens) strategy of functioning of the influenza A virus genome.
PMID- 28510128
TI - Specific character of bacterial biodegradation of polyhydroxyalkanoates with
different chemical structure in soil.
AB - The study addresses the influence of the physicochemical properties of the
reserve cellular macromolecules (polyhydroxyalkanoates, PHA) with different
chemical composition on their biodegradation in the agro-transformed field soil
of the Siberian region (Krasnoyarsk Territory, Russia). It was shown that the
degradation of the PHA samples depends on the degree of polymer crystallinity
(Cx). For the first time, it was shown that the range of PHA-degrading
microorganisms differs for each of PHA types. The study defines the primary
degraders specific to each PHA type and common to all types of examined polymers.
PMID- 28510129
TI - LTR sequence of the MDG4 retrotransposon contains the MAD protein binding site
that affects the east-dependent repression.
AB - Earlier, we showed in a model system of the yellow gene of D. melanogaster that
an increase in the EAST protein concentration leads to repression in bristles,
the mechanism of which remained obscure. In this study, an inverted repeat was
localized by genetic methods in the long terminal repeat (LTR) sequence of the
MDG4 retrotransposon. This repeat includes the binding site for the Mad protein
the key component of the of TGF-beta/BMP signaling cascade. The results of this
work suggest that the Mad protein recruits to chromatin a regulatory complex that
functionally interacts with the EAST protein. This complex either itself
suppresses the yellow gene expression in bristles or moves the transgene to the
nuclear regions with a high concentration of transcription repression factors.
PMID- 28510130
TI - The penetration of 5-oxo-Pro-Arg-Pro into the brain and the major metabolic
pathways of this peptide in the rat brain and blood at the intranasal and
intravenous administration.
AB - It was shown that the neuroactive peptide 5-oxo-Pro-Arg-Pro (5-oxo-PRP) is
detected in the brain in the time interval of 5-120 min after it was
intravenously or intranasally administered to rats; the maximum concentration of
labeled tripeptide in these modes of administration was observed after 30 and 10
min, respectively. A significant difference in the concentrations of 5-oxo-PRP in
the blood and brain (the latter was 50 times lower) during intravenous
administration indicates a relatively low permeability of the peptide across the
blood-brain barrier. Pharmacokinetic data analysis showed that, when administered
intranasally, approximately 45% of the total number of 5-oxo-PRP detectable in
the brain in the entire period of study enters via transport from the nasal
cavity, and the rest of the peptide enters through the blood-brain barrier from
the blood stream. It was found that 5-oxo-PRP in rats is rapidly metabolized
forming proteolytic products, mainly amino acids, and degradation products,
presumably oxidized these amino acids.
PMID- 28510131
TI - Generation of radical form of dipyridamole at illumination of photosynthetic
reaction centers of Rb. sphaeroides.
AB - The study of the effect of vasodilator, antiplatelet agent, and inhibitor P
glycoprotein dipyridamole (DIP) on the functioning of the transmembrane protein
of the reaction center (RC) of Rb. sphaeroides showed that the activation of RC
by constant light generates the DIP radical cation, which significantly affects
the kinetics of recombination of charges divided between photoactive
bacteriochlorophyll and quinone acceptors. Thus, the antioxidant properties of
DIP may affect the functional activity of membrane proteins, and this apparently
should be taken into account in the studies of the mechanisms of therapeutic
action of this drug.
PMID- 28510132
TI - Methyl-beta-cyclodextrin modulates thapsigargin-induced store-dependent Ca2+
entry in macrophages.
AB - Using Fura-2AM microfluorimetry, we have shown for the first time that
preincubation of macrophages with methyl-beta-cyclodextrin, inducing cholesterol
extraction from membranes and raft disruption, leads to significant inhibition of
thapsigargin-induced store-dependent Ca2+ entry in rat peritoneal macrophages. In
contrast, macrophage treatment with methyl-beta-cyclodextrin after Ca2+ entry
mechanisms were activated by store depletion by thapsigargin application leads to
potentiation of subsequent store-dependent Ca2+ entry. The results suggest that
intact lipid rafts are necessary for the activation but not the maintenance of
store-dependent Ca2+ entry in macrophages.
PMID- 28510133
TI - Analysis of immune-biochemical indicators to assess the risk of developing
cardiological pathology.
AB - Prognostic immuno-biochemical tests to assess the severity of the condition of
patients with cardiac diseases were developed. A comparative analysis of clinical
and laboratory blood parameters, which are used in practice for the diagnosis and
prognosis of diseases, and an analysis of the content of natural antibodies (n
Abs) to beta-endorphin, bradykinin, histamine, dopamine, and serotonin were
performed. A significant correlation between the level of n-Abs, the main
biochemical parameters, and the content of blood corpuscles was revealed. The
practical importance of the combined use of immunological and biochemical tests
to increase the reliability of prediction of the severity of heart pathologies
was established.
PMID- 28510134
TI - Paramagnetics melanin and Mn2+ in black soldier fly Hermetia illucens.
AB - Larva, prepupa (last instar larva), pupa, and an empty shell of pupa after
hatching of the black soldier fly Hermetia illucens contain eumelanin, an active
synthesis of which is observed at the prepupal stage, which is probably due to
the release of prepupa from the feed substrate thickness to the open space for
pupation. It was shown for the first time that prepupa contains high quantities
of the magnetically active form of manganese Mn2+. This fact indicates that Mn2+
stimulates the copper-containing tyrosinase-the key enzyme in the synthesis of
melanin in the period of migration and adaptation of the insect to the solar
radiation.
PMID- 28510135
TI - Immune response to Vi-antigen of Salmonella typhi is dependent on introduction of
positive charge and shape of charged group into polysaccharide.
AB - A model of a controlled conversion of polysaccharide Vi-antigen of S. typhi into
zwitterionic antigen is proposed. The immunological properties of modifications
of this antigen conjugated to a protein support were studied.
PMID- 28510136
TI - Identification and expression analysis of chitinase genes in parasitic plant
Monotropa hypopitys.
AB - Genes encoding six chitinases, five of which belong to classes I (MhCHI3 and
MhCHI4), IV (MhCHI1), V (MhCHI5), and VII (MhCHI2), were identified in the
transcriptome of the parasitic mixoheterotrophic plant Monotropa hypopitys. The
transcription level of MhCHI5 and MhCHI1 was low; however, in the leaves (bracts)
and roots it was higher than in flowers. MhCHI4 transcripts were detected
primarily in the flowers and were almost absent in the roots, whereas the
expression level of MhCHI3 was relatively high in all organs but maximum in the
leaves (bracts).
PMID- 28510137
TI - Possible mechanism of bursting suppression in nociceptive neurons.
AB - The use of the mathematical model of rat nociceptive neuron membrane allowed us
to predict a new mechanism of suppression of ectopic bursting discharges, which
arise in neurons of dorsal root ganglia and are one of the causes of neuropathic
pain. The treatment with comenic acid leads to switching off the ectopic bursting
discharges due to a decrease in the effective charge transferring via the
activation gating structure of the slow sodium channels (Na V1.8a). Comenic acid
is a drug substance of a new non-opioid analgesic [1] Thus, this analgesic not
only reduces the frequency of rhythmic discharges of nociceptive neuron membrane
[2] but also it suppresses its ectopic bursting discharges.
PMID- 28510138
TI - Antitumor efficacy of Auger electron emitter 111In delivered by modular
nanotransporter into the nuclei of cells with folate receptor overexpression.
AB - A new modular nanotransporter (MNT) for the delivery of anticancer agents into
the nuclei of cells with folate receptor overexpression was created. An effective
method for acceding labeling of this MNT with Auger electron emitter 111In has
been developed. A significant therapeutic effect was observed after a single
intratumoral injection of the new 111In-labeled MNT to mice grafted with human
cervical carcinoma characterized by folate receptor overexpression.
PMID- 28510139
TI - Development of target delivery system based on actinomycin class drugs and
recombinant alpha-fetoprotein.
AB - A recombinant alpha-fetoprotein (rAFP) was obtained in the yeast P. pastoris
system, and its functional activity was confirmed. A method for producing polymer
particles loaded with dactinomycin was developed, and a conjugate of these
nanoparticles with rAFP was synthesized. The efficiency of the obtained conjugate
on the HeLa, SKOV3, and MG-63 tumor cells and the absence of toxicity on the
normal cells was shown. Experiments in vivo demonstrated a significant increase
in the antitumor efficacy of the conjugate at a lower general toxicity as
compared to the commercially available dactinomycin.
PMID- 28510140
TI - Nuclear receptors EcR, Usp, E75, DHR3, and ERR regulate transcription of ecdysone
cascade genes.
AB - We found that an increase in the expression level of E75, DHR3, and ERR increases
the degree of activation of dhr3 and hr4 genes in Drosophila S2 cells. We also
detected a repressing effect of these nuclear receptors on the basal
transcription level of these genes. This is the first study to show the ability
of nuclear receptors E75, DHR3, and ERR to function as activators or repressors
depending on external conditions. We also confirmed the existence of the
interaction of all studied nuclear receptors with the promoters of dhr3 and hr4
genes of the ecdysone cascade in vivo.
PMID- 28510141
TI - Sunscreens: An Update.
AB - Sunscreens have been widely used by the general public for their photoprotective
properties, including prevention of photocarcinogenesis and photoaging and
management of photodermatoses. It is important to emphasize to consumers the
necessity of broad-spectrum protection, with coverage of both ultraviolet A (320
400 nm) and ultraviolet B (290-320 nm) radiation. This review discusses the
benefits of sunscreen, different ultraviolet filters, sunscreen regulations and
controversies, the importance of broad-spectrum protection, issues of
photostability and formulation, and patient education and compliance.
PMID- 28510142
TI - Local heating of molecular motors using single carbon nanotubes.
AB - Temperature globally affects all chemical processes and biomolecules in living
cells. Elevating the temperature of an entire cell accelerates so many
biomolecular reactions simultaneously that it is difficult to distinguish the
various mechanisms involved. The ability to localize temperature changes to the
nanometer range within a cell could provide a powerful new tool for regulating
biomolecular activity at the level of individual molecules. The search for a
nanoheater for biological research has prompted experiments with carbon nanotubes
(CNTs), which have the highest conductivity of any known material. The adsorption
of skeletal muscle myosin molecules along the length of single multi-walled CNTs
(~10 MUm) has allowed researchers to observe the ATP-driven sliding of
fluorescently labeled actin filaments. In one study, red-laser irradiation
focused on one end of a myosin-coated CNT was used to heat myosin motors locally
without directly heating the surrounding water; this laser irradiation instantly
accelerated the actin-filament sliding speeds from ~6 to ~12 MUm/s in a
reversible manner, indicating a local, real-time heating of myosin motors by
approximately Delta12 K. Calculation of heat transfer using the finite element
method, based on the estimated temperature along a single CNT with a diameter of
170 nm, indicated a high thermal conductivity of ~1540 Wm-1K-1 in solution,
consistent with values measured in vacuum in earlier studies. Temperature
distribution indicated by half-decrease distances was ~3660 nm along the length
of the CNT and ~250 nm perpendicular to the length. These results suggest that
single-CNT-based heating at the nanometer- or micrometer-range could be used to
regulate various biomolecules in many areas of biological, physical, and chemical
research.
PMID- 28510143
TI - The structural stability and catalytic activity of DNA and RNA oligonucleotides
in the presence of organic solvents.
AB - Organic solvents and apolar media are used in the studies of nucleic acids to
modify the conformation and function of nucleic acids, to improve solubility of
hydrophobic ligands, to construct molecular scaffolds for organic synthesis, and
to study molecular crowding effects. Understanding how organic solvents affect
nucleic acid interactions and identifying the factors that dominate solvent
effects are important for the creation of oligonucleotide-based technologies.
This review describes the structural and catalytic properties of DNA and RNA
oligonucleotides in organic solutions and in aqueous solutions with organic
cosolvents. There are several possible mechanisms underlying the effects of
organic solvents on nucleic acid interactions. The reported results emphasize the
significance of the osmotic pressure effect and the dielectric constant effect in
addition to specific interactions with nucleic acid strands. This review will
serve as a guide for the selection of solvent systems based on the purpose of the
nucleic acid-based experiments.
PMID- 28510144
TI - Enhanced sampling simulations to construct free-energy landscape of protein
partner substrate interaction.
AB - Molecular dynamics (MD) simulations using all-atom and explicit solvent models
provide valuable information on the detailed behavior of protein-partner
substrate binding at the atomic level. As the power of computational resources
increase, MD simulations are being used more widely and easily. However, it is
still difficult to investigate the thermodynamic properties of protein-partner
substrate binding and protein folding with conventional MD simulations. Enhanced
sampling methods have been developed to sample conformations that reflect
equilibrium conditions in a more efficient manner than conventional MD
simulations, thereby allowing the construction of accurate free-energy
landscapes. In this review, we discuss these enhanced sampling methods using a
series of case-by-case examples. In particular, we review enhanced sampling
methods conforming to trivial trajectory parallelization, virtual-system coupled
multicanonical MD, and adaptive lambda square dynamics. These methods have been
recently developed based on the existing method of multicanonical MD simulation.
Their applications are reviewed with an emphasis on describing their practical
implementation. In our concluding remarks we explore extensions of the enhanced
sampling methods that may allow for even more efficient sampling.
PMID- 28510145
TI - Isopeptide bond in collagen- and fibrinogen-binding MSCRAMMs.
AB - The internal isopeptide bonds are amide bonds formed autocatalytically between
the side chains of Lys and Asn/Asp residues and have been discovered recently.
These bonds are well conserved in Gram-positive bacterial pilin proteins and are
also observed over a wide range of Gram-positive bacterial surface proteins. The
presence of these bonds confers the pilus subunits with remarkable properties in
terms of thermal stability and resistance to proteases. Like pili, microbial
surface components recognizing adhesive matrix molecules (MSCRAMMs) are also
surface proteins found only in Gram-positive bacteria. They specifically interact
with the extracellular matrix (ECM) molecules like collagen, fibrinogen,
fibronectin, laminin, etc. Many biophysical and biochemical studies have been
carried out to characterize the isopeptide bonds in pili proteins from Gram
positive bacteria, but no attempts have been made to study the isopeptide bonds
in MSCRAMMs. This short review aims to study the significance of the isopeptide
bonds in relation to their function, by analyzing the crystal structures of
collagen- and fibrinogen-binding MSCRAMMs. In this analysis, interestingly, we
observed that the putative isopeptide bonds are restricted to the collagen
binding MSCRAMMs. Based on analogy with bacterial pilus subunits, we hypothesize
that the collagen-binding MSCRAMMs possessing putative isopeptide bonds exhibit
similar structural properties, which could help the bacteria in colonizing the
host and provide resistance against host-defense mechanisms.
PMID- 28510147
TI - The evolution of Biophysical Reviews.
PMID- 28510146
TI - PWWP domains and their modes of sensing DNA and histone methylated lysines.
AB - Chromatin plays an important role in gene transcription control, cell cycle
progression, recombination, DNA replication and repair. The fundamental unit of
chromatin, the nucleosome, is formed by a DNA duplex wrapped around an octamer of
histones. Histones are susceptible to various post-translational modifications,
covalent alterations that change the chromatin status. Lysine methylation is one
of the major post-translational modifications involved in the regulation of
chromatin function. The PWWP domain is a member of the Royal superfamily that
functions as a chromatin methylation reader by recognizing both DNA and histone
methylated lysines. The PWWP domain three-dimensional structure is based on an N
terminal hydrophobic beta-barrel responsible for histone methyl-lysine binding,
and a C-terminal alpha-helical domain. In this review, we set out to discuss the
most recent literature on PWWP domains, focusing on their structural features and
the mechanisms by which they specifically recognize DNA and histone methylated
lysines at the level of the nucleosome.
PMID- 28510148
TI - Glucose transporters: physiological and pathological roles.
AB - Glucose is a primary energy source for most cells and an important substrate for
many biochemical reactions. As glucose is a need of each and every cell of the
body, so are the glucose transporters. Consequently, all cells express these
important proteins on their surface. In recent years developments in genetics
have shed new light on the types and physiology of various glucose transporters,
of which there are two main types-sodium-glucose linked transporters (SGLTs) and
facilitated diffusion glucose transporters (GLUT)-which can be divided into many
more subclasses. Transporters differ in terms of their substrate specificity,
distribution and regulatory mechanisms. Glucose transporters have also received
much attention as therapeutic targets for various diseases. In this review, we
attempt to present a simplified view of this complex topic which may be of
interest to researchers involved in biochemical and pharmacological research.
PMID- 28510150
TI - Editorial.
PMID- 28510149
TI - Structural aspects of nucleic acid-sensing Toll-like receptors.
AB - Invading pathogens elicit potent immune responses in cells through interactions
between structurally conserved molecules derived from the pathogens and
specialized innate immune receptors such as the Toll-like receptors (TLRs).
Nucleic acid is one of the principal TLR ligands. Nucleic acid-sensing TLRs
recognize an array of nucleic acids, including double-stranded RNA, single
stranded RNA, and DNAs with specific sequence motifs. Although ligand-induced
dimerization is commonly observed followed by TLR activation, both the specific
recognition mechanisms and the ligand-receptor interactions vary among different
TLRs. In this review, we highlight our current understanding of how these
receptors recognize their cognate ligands based on the recent advances in
structural biology.
PMID- 28510152
TI - Biochemical characterization of breast tumors by in vivo and in vitro magnetic
resonance spectroscopy (MRS).
AB - Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) have
evolved as sensitive tools for anatomic and metabolic evaluation of breast
cancer. In vivo MRS studies have documented the presence of choline containing
compounds (tCho) as a reliable biochemical marker of malignancy and also useful
for monitoring the tumor response to therapy. Recent studies on the absolute
quantification of tCho are expected to provide cut-off values for discrimination
of various breast pathologies. Addition of MRS investigation was also reported to
increase the specificity of MRI. Further, ex vivo and in vitro MRS studies of
intact tissues and tissue extracts provided several metabolites that were not be
detected in vivo and provided insight into underlying biochemistry of the disease
processes. In this review, we present briefly the role of various 1H MRS methods
used in breast cancer research and their potential in relation to diagnosis,
monitoring of therapeutic response and metabolism.
PMID- 28510154
TI - The role of beta-sheets in the structure and assembly of keratins.
AB - X-ray diffraction, infrared and electron microscope studies of avian and
reptilian keratins, and of stretched wool and hair, have played a central role in
the development of models for the beta-conformation in proteins. Both alpha- and
beta-keratins contain sequences that are predicted to adopt a beta-conformation
and these are believed to play an important part in the assembly of the filaments
and in determining their mechanical properties. Interactions between the small
beta-sheets in keratins provide a simple mechanism through which shape and
chemical complementarity can mediate the assembly of molecules into highly
specific structures. Interacting beta-sheets in crystalline proteins are often
related to one another by diad symmetry and the data available on feather keratin
suggest that the filament is assembled from dimers in which the beta-sheets are
related by a perpendicular diad. The most detailed model currently available is
for feather and reptilian keratin but the presence of related beta-structural
forms in mammalian keratins is also noted.
PMID- 28510151
TI - CFTR structure and function: is there a role in the kidney?
AB - Cystic fibrosis (CF) is a lethal autosomal recessive genetic disease caused by
mutations in the CF transmembrane conductance regulator (CFTR). Mutations in the
CFTR gene may result in a defective protein processing that leads to changes in
function and regulation of this chloride channel. Despite of the expression of
CFTR in the kidney, patients with CF do not present major renal dysfunction, but
it is known that both the urinary excretion of proteins and renal capacity to
concentrate and dilute urine are altered in these patients. CFTR mRNA is
expressed in all nephron segments of rat and human, and this abundance is more
prominent in renal cortex and outer medulla renal areas. CFTR protein was
detected in apical surface of both proximal and distal tubules of rat kidney but
not in the outer medullary collecting ducts. Studies have demonstrated that CFTR
does not only transport Cl- but also ATP. ATP transport by CFTR could be involved
in the control of other ion transporters such as Na+ (ENaC) and K+ (renal outer
medullary potassium) channels, especially in TAL and CCD. In the kidney, CFTR
also might be involved in the endocytosis of low-molecular-weight proteins by
proximal tubules. This review is focused on the CFTR function and structure, its
role in the renal physiology, and its modulation by hormones involved in the
control of extracellular fluid volume.
PMID- 28510153
TI - Intercalated discs: multiple proteins perform multiple functions in non-failing
and failing human hearts.
AB - The intercalated disc (ICD) occupies a central position in the transmission of
force, electrical continuity and chemical communication between cardiomyocytes.
Changes in its structure and composition are strongly implicated in heart
failure. ICD functions include: maintenance of electrical continuity across the
ICD; physical links between membranes and the cytoskeleton; intercellular
adhesion; maintenance of ICD structure and function; and growth. About 200 known
proteins are associated with ICDs, 40% of which change in disease. We
systemically reviewed cardiac immunohistochemical data on the Human Protein Atlas
(HPA) web site, ExPASy protein binding data and published papers on ICDs. We
identified 43 proteins not previously reported, and confirmed 37 proteins that
have previously been described. In addition, 102 proteins not present on the HPA
web site but were described in ICDs in the literature. We group these into
clusters that demonstrate functionally interactive groups of proteins
demonstrating that ICDs play a key role in cardiomyocyte function.
PMID- 28510155
TI - A historical perspective of the biophysics of the thrombin-heparin system: an
example of nonspecific binding and the consequent parking problem in action.
AB - Difficulties are encountered in the thermodynamic characterization of
interactions between a protein ligand and a linear acceptor, such as a
polynucleotide or a polysaccharide, because of the involvement of more than one
unit of the polymer chain in each attachment of a protein molecule. Complications
arise from the fact that random attachment of ligand to the polymer chain, each
unit of which is a potential binding site, initially leads to suboptimal location
of protein molecules along the polymer chain-a situation that has to be rectified
before the attainment of thermodynamic equilibrium can be realized. Kinetic as
well as thermodynamic consequences of such nonspecific binding, termed the
parking problem, therefore need to be considered in any quantitative
characterization of the interaction between a large ligand and a linear polymer
acceptor chain. Results for the thrombin-heparin interaction have been used to
illustrate a thermodynamic characterization of nonspecific binding that takes
into account these consequences of the parking problem.
PMID- 28510156
TI - Effects of macromolecular crowding agents on protein folding in vitro and in
silico.
AB - Proteins fold and function inside cells which are environments very different
from that of dilute buffer solutions most often used in traditional experiments.
The crowded milieu results in excluded-volume effects, increased bulk viscosity
and amplified chances for inter-molecular interactions. These environmental
factors have not been accounted for in most mechanistic studies of protein
folding executed during the last decades. The question thus arises as to how
these effects-present when polypeptides normally fold in vivo-modulate protein
biophysics. To address excluded volume effects, we use synthetic macromolecular
crowding agents, which take up significant volume but do not interact with
proteins, in combination with strategically selected proteins and a range of
equilibrium and time-resolved biophysical (spectroscopic and computational)
methods. In this review, we describe key observations on macromolecular crowding
effects on protein stability, folding and structure drawn from combined in vitro
and in silico studies. As expected based on Minton's early predictions, many
proteins (apoflavodoxin, VlsE, cytochrome c, and S16) became more
thermodynamically stable (magnitude depends inversely on protein stability in
buffer) and, unexpectedly, for apoflavodoxin and VlsE, the folded states changed
both secondary structure content and, for VlsE, overall shape in the presence of
macromolecular crowding. For apoflavodoxin and cytochrome c, which have complex
kinetic folding mechanisms, excluded volume effects made the folding energy
landscapes smoother (i.e., less misfolding and/or kinetic heterogeneity) than in
buffer.
PMID- 28510157
TI - Soft interactions and crowding.
AB - The intracellular milieu is complex, heterogeneous and crowded-an environment
vastly different from dilute solutions in which most biophysical studies are
performed. The crowded cytoplasm excludes about a third of the volume available
to macromolecules in dilute solution. This excluded volume is the sum of two
parts: steric repulsions and chemical interactions, also called soft
interactions. Until recently, most efforts to understand crowding have focused on
steric repulsions. Here, we summarize the results and conclusions from recent
studies on macromolecular crowding, emphasizing the contribution of soft
interactions to the equilibrium thermodynamics of protein stability. Despite
their non-specific and weak nature, the large number of soft interactions present
under many crowded conditions can sometimes overcome the stabilizing steric,
excluded volume effect.
PMID- 28510158
TI - Assessment and significance of protein-protein interactions during development of
protein biopharmaceuticals.
AB - Early development of protein biotherapeutics using recombinant DNA technology
involved progress in the areas of cloning, screening, expression and
recovery/purification. As the biotechnology industry matured, resulting in
marketed products, a greater emphasis was placed on development of formulations
and delivery systems requiring a better understanding of the chemical and
physical properties of newly developed protein drugs. Biophysical techniques such
as analytical ultracentrifugation, dynamic and static light scattering, and
circular dichroism were used to study protein-protein interactions during various
stages of development of protein therapeutics. These studies included
investigation of protein self-association in many of the early development
projects including analysis of highly glycosylated proteins expressed in
mammalian CHO cell cultures. Assessment of protein-protein interactions during
development of an IgG1 monoclonal antibody that binds to IgE were important in
understanding the pharmacokinetics and dosing for this important biotherapeutic
used to treat severe allergic IgE-mediated asthma. These studies were extended to
the investigation of monoclonal antibody-antigen interactions in human serum
using the fluorescent detection system of the analytical ultracentrifuge.
Analysis by sedimentation velocity analytical ultracentrifugation was also used
to investigate competitive binding to monoclonal antibody targets. Recent
development of high concentration protein formulations for subcutaneous
administration of therapeutics posed challenges, which resulted in the use of
dynamic and static light scattering, and preparative analytical
ultracentrifugation to understand the self-association and rheological properties
of concentrated monoclonal antibody solutions.
PMID- 28510161
TI - Protein-protein interactions in a crowded environment.
AB - Protein-protein interactions are important in many essential biological
functions, such as transcription, translation, and signal transduction. Much
progress has been made in understanding protein-protein association in dilute
solution via experimentation and simulation. Cells, however, contain various
macromolecules, such as DNA, RNA, proteins, among many others, and a myriad of
non-specific interactions (usually weak) are present between these cellular
constituents. In this review article, we describe the important developments in
recent years that have furthered our understanding and even allowed prediction of
the consequences of macromolecular crowding on protein-protein interactions. We
outline the development of our crowding theory that can predict the change in
binding free energy due to crowding quantitatively for both repulsive and
attractive protein-crowder interactions. One of the most important findings from
our recent work is that weak attractive interactions between crowders and
proteins can actually destabilize protein complex formation as opposed to the
commonly assumed stabilizing effect predicted based on traditional crowding
theories that only account for the entropic-excluded volume effects. We also
discuss the implications of macromolecular crowding on the population of
encounter versus specific native complex.
PMID- 28510159
TI - The loop hypothesis: contribution of early formed specific non-local interactions
to the determination of protein folding pathways.
AB - The extremely fast and efficient folding transition (in seconds) of globular
proteins led to the search for some unifying principles embedded in the physics
of the folding polypeptides. Most of the proposed mechanisms highlight the role
of local interactions that stabilize secondary structure elements or a folding
nucleus as the starting point of the folding pathways, i.e., a "bottom-up"
mechanism. Non-local interactions were assumed either to stabilize the nucleus or
lead to the later steps of coalescence of the secondary structure elements. An
alternative mechanism was proposed, an "up-down" mechanism in which it was
assumed that folding starts with the formation of very few non-local interactions
which form closed long loops at the initiation of folding. The possible
biological advantage of this mechanism, the "loop hypothesis", is that the
hydrophobic collapse is associated with ordered compactization which reduces the
chance for degradation and misfolding. In the present review the experiments,
simulations and theoretical consideration that either directly or indirectly
support this mechanism are summarized. It is argued that experiments monitoring
the time-dependent development of the formation of specifically targeted early
formed sub-domain structural elements, either long loops or secondary structure
elements, are necessary. This can be achieved by the time-resolved FRET-based
"double kinetics" method in combination with mutational studies. Yet, attempts to
improve the time resolution of the folding initiation should be extended down to
the sub-microsecond time regime in order to design experiments that would resolve
the classes of proteins which first fold by local or non-local interactions.
PMID- 28510160
TI - Macromolecular interactions of the bacterial division FtsZ protein: from
quantitative biochemistry and crowding to reconstructing minimal divisomes in the
test tube.
AB - The division of Escherichia coli is an essential process strictly regulated in
time and space. It requires the association of FtsZ with other proteins to
assemble a dynamic ring during septation, forming part of the functionally active
division machinery, the divisome. FtsZ reversibly interacts with FtsA and ZipA at
the cytoplasmic membrane to form a proto-ring, the first molecular assembly of
the divisome, which is ultimately joined by the rest of the division-specific
proteins. In this review we summarize the quantitative approaches used to study
the activity, interactions, and assembly properties of FtsZ under well-defined
solution conditions, with the aim of furthering our understanding of how the
behavior of FtsZ is controlled by nucleotides and physiological ligands. The
modulation of the association and assembly properties of FtsZ by excluded-volume
effects, reproducing in part the natural crowded environment in which this
protein has evolved to function, will be described. The subsequent studies on the
reactivity of FtsZ in membrane-like systems using biochemical, biophysical, and
imaging technologies are reported. Finally, we discuss the experimental
challenges to be met to achieve construction of the minimum protein set needed to
initiate bacterial division, without cells, in a cell-like compartment. This
integrated approach, combining quantitative and synthetic strategies, will help
to support (or dismiss) conclusions already derived from cellular and molecular
analysis and to complete our understanding on how bacterial division works.
PMID- 28510162
TI - Foreword to the biophysics of protein-protein and protein-ligand interactions in
dilute and crowded media-a special issue in honor of Allen Minton's 70th
birthday.
PMID- 28510163
TI - Ratchets, red cells, and metastability.
AB - Sickle cell disease is a genetic disorder in which a negatively charged glutamic
acid is replaced by a hydrophobic valine on the surface of the hemoglobin
molecule, leading to polymerization of the deoxygenated form, and resulting in
microvascular obstruction. Because of the high volume occupancy under which
polymerization occurs physiologically, this process has been an exemplar in the
study of excluded volume effects on assembly. More recently, we have identified
yet another type of crowding effect involving the obstruction of the ends at
which the polymers grow as a consequence of the dense arrays in which these
polymers form. This makes such solutions metastable, and leads to Brownian
ratchet behavior in which pressure is exerted outward when the gel occupies a
finite volume, as in an emulsion or red cell. Such behavior is capable of holding
sickled cells in place in the microcirculation against weak pressure
differentials (hundreds of Pa), but not against the typical pressures found in
vivo.
PMID- 28510164
TI - Entropic stabilization of the folded states of RNA due to macromolecular
crowding.
AB - We review the effects of macromolecular crowding on the folding of RNA by
considering the simplest scenario when excluded volume interactions between
crowding particles and RNA dominate. Using human telomerase enzyme as an example,
we discuss how crowding can alter the equilibrium between pseudoknot and hairpin
states of the same RNA molecule-a key aspect of crowder-RNA interactions. We
summarize data showing that the crowding effect is significant only if the size
of the spherical crowding particle is smaller than the radius of gyration of the
RNA in the absence of crowding particles. The implication for function of the
wild type and mutants of human telomerase is outlined by using a relationship
between enzyme activity and its conformational equilibrium. In addition, we
discuss the interplay between macromolecular crowding and ionic strength of the
RNA buffer. Finally, we briefly review recent experiments which illustrate the
connection between excluded volume due to macromolecular crowding and the
thermodynamics of RNA folding.
PMID- 28510166
TI - A brief look back at 45 years of research in physical biochemistry.
PMID- 28510167
TI - Note on "Protein dynamics and the allosteric transitions of pentameric receptor
channels" by Jean-Pierre Changeux.
PMID- 28510165
TI - Protein interactions in the assembly of the tail of bacteriophage T4.
AB - Protein interactions in the assembly of the baseplate have been investigated. The
baseplate of the phage T4 tail consists of a hub and six wedges which surround
the former. Both reversible and irreversible interactions were found. Reversible
association includes gp5 and gp27 (gp: gene product) which form a complex in a pH
dependent manner and gp18 polymerization, i.e. the tail sheath formation depends
on the ionic strength. These reversible interactions were followed by
irreversible or tight binding which pulls the whole association reaction to
complete the assembly. The wedge assembly is strictly ordered which means that if
one of the seven wedge proteins is missing, the assembly proceeds to that point
and the remaining molecules stay non-associated. The strictly sequential assembly
pathway is suggested to be materialized by successive conformational change upon
binding, which can be shown by proteolytic probe.
PMID- 28510168
TI - Nanoscale protein domain motion and long-range allostery in signaling proteins-a
view from neutron spin echo spectroscopy.
AB - Many cellular proteins are multi-domain proteins. Coupled domain-domain
interactions in these multidomain proteins are important for the allosteric relay
of signals in the cellular signaling networks. We have initiated the application
of neutron spin echo spectroscopy to the study of nanoscale protein domain
motions on submicrosecond time scales and on nanometer length scale. Our NSE
experiments reveal the activation of protein domain motions over a long distance
of over more than 100 A in a multidomain scaffolding protein NHERF1 upon binding
to another protein, Ezrin. Such activation of nanoscale protein domain motions is
correlated with the allosteric assembly of multi-protein complexes by NHERF1 and
Ezrin. Here, we summarize the theoretical framework that we have developed, which
uses simple concepts from nonequilibrium statistical mechanics to interpret the
NSE data, and employs a mobility tensor to describe nanoscale protein domain
motion. Extracting nanoscale protein domain motion from the NSE does not require
elaborate molecular dynamics simulations, nor complex fits to rotational motion,
nor elastic network models. The approach is thus more robust than multiparameter
techniques that require untestable assumptions. We also demonstrate that an
experimental scheme of selective deuteration of a protein subunit in a complex
can highlight and amplify specific domain dynamics from the abundant global
translational and rotational motions in a protein. We expect NSE to provide a
unique tool to determine nanoscale protein dynamics for the understanding of
protein functions, such as how signals are propagated in a protein over a long
distance to a distal domain.
PMID- 28510169
TI - Global low-frequency motions in protein allostery: CAP as a model system.
AB - Allostery is a fundamental process by which ligand binding to a protein alters
its activity at a distant site. There is considerable evidence that allosteric
cooperativity can be communicated by the modulation of protein dynamics without
conformational change. The Catabolite Activator Protein (CAP) of Escherichia coli
is an important experimental exemplar for entropically driven allostery. Here we
discuss recent experimentally supported theoretical analysis that highlights the
role of global low-frequency dynamics in allostery in CAP and identify how
allostery arises as a natural consequence of changes in global low-frequency
protein fluctuations on ligand binding.
PMID- 28510170
TI - Relaxation dispersion NMR spectroscopy for the study of protein allostery.
AB - Allosteric transmission of information between distant sites in biological
macromolecules often involves collective transitions between active and inactive
conformations. Nuclear magnetic resonance (NMR) spectroscopy can yield detailed
information on these dynamics. In particular, relaxation dispersion techniques
provide structural, dynamic, and mechanistic information on conformational
transitions occurring on the millisecond to microsecond timescales. In this
review, we provide an overview of the theory and analysis of Carr-Purcell-Meiboom
Gill (CPMG) relaxation dispersion NMR experiments and briefly describe their
application to the study of allosteric dynamics in the homeodomain from the PBX
transcription factor (PBX-HD). CPMG NMR data show that local folding (helix/coil)
transitions in one part of PBX-HD help to communicate information between two
distant binding sites. Furthermore, the combination of CPMG and other spin
relaxation data show that this region can also undergo local misfolding,
reminiscent of conformational ensemble models of allostery.
PMID- 28510171
TI - Terahertz optical measurements of correlated motions with possible allosteric
function.
AB - A suggested mechanism for allosteric response is the distortion of the energy
landscape with agonist binding changing the protein structure's access to
functional configurations. Intramolecular vibrations are indicative of the energy
landscape and may have trajectories that enable functional conformational change.
Here, we discuss the development of an optical method to measure the
intramolecular vibrations in proteins, namely, crystal anisotropy terahertz
microscopy, and the various approaches which can be used to identify the spectral
data with specific structural motions.
PMID- 28510172
TI - Contrasting roles of dynamics in protein allostery: NMR and structural studies of
CheY and the third PDZ domain from PSD-95.
AB - Allosteric regulation is a ubiquitous phenomenon exploited in biological
processes to control cells in a myriad of ways. It is also of emerging interest
in the design of functional proteins and therapeutics. Even though allostery was
proposed over 50 years ago and has been studied intensively from a structural
perspective, many key details of allosteric mechanisms remain mysterious. Over
the last decade significant attention has been paid to the "dynamic component" of
allostery, as opposed to the analysis of rigid structures. Nuclear magnetic
resonance spectroscopy and its ability to detect conformationally dynamic
processes at atomic resolution have played an important role in expanding our
understanding of allosteric mechanisms and opening up new questions. This article
focuses on work that highlights how protein dynamics can factor into allosteric
processes in distinct ways. Two cases are contrasted. The first considers the
"traditionally allosteric" protein CheY, which undergoes a conformational change
as a key element of its allostery. The second considers the more rarely observed
"dynamic allostery" in a PDZ domain, in which allosteric behavior arises from
changes in internal structural dynamics. Interestingly, the dynamic processes in
these two contrasting examples occur on different timescales. In the case of the
PDZ domain, subsequent experimental and computational work is reviewed to reveal
a more complete picture of this interesting case of allostery.
PMID- 28510173
TI - Disordered allostery: lessons from glucocorticoid receptor.
AB - Allostery is a biological regulation mechanism of significant importance in cell
signaling, metabolism, and disease. Although the ensemble basis of allostery has
been known for years, only recently has emphasis shifted from interpreting
allosteric mechanism in terms of discrete structural pathways to ones that focus
on the statistical nature of the signal propagation process, providing a vehicle
to unify allostery in structured, dynamic, and disordered systems. In particular,
intrinsically disordered (ID) proteins (IDPs), which lack a unique, stable
structure, have been directly demonstrated to exhibit allostery in numerous
systems, a reality that challenges traditional structure-based models that focus
on allosteric pathways. In this chapter, we will discuss the historical context
of allostery and focus on studies from human glucocorticoid receptor (GR), a
member of the steroid hormone receptor (SHR) family. The numerous translational
isoforms of the disordered N-terminal domain of GR consist of coupled
thermodynamic domains that contribute to the delicate balance of states in the
ensemble and hence in vivo activity. The data are quantitatively interpreted
using the ensemble allosteric model (EAM) that considers only the intrinsic and
measurable energetics of allosteric systems. It is demonstrated that the EAM
provides mechanistic insight into the distribution of states in solution and
provides an interpretation for how certain translational isoforms of GR display
enhanced and repressed transcriptional activities. The ensemble nature of
allostery illuminated from these studies lends credence to the EAM and provides
ground rules for allostery in all systems.
PMID- 28510174
TI - The role of slow and fast protein motions in allosteric interactions.
AB - Allostery is fundamentally thermodynamic in nature. Long-range communication in
proteins may be mediated not only by changes in the mean conformation with
enthalpic contribution but also by changes in dynamic fluctuations with entropic
contribution. The important role of protein motions in mediating allosteric
interactions has been established by NMR spectroscopy. By using CAP as a model
system, we have shown how changes in protein structure and internal dynamics can
allosterically regulate protein function and activity. The results indicate that
changes in conformational entropy can give rise to binding enhancement, binding
inhibition, or have no effect in the expected affinity, depending on the
magnitude and sign of enthalpy-entropy compensation. Moreover, allosteric
interactions can be regulated by the modulation a low-populated conformation
states that serve as on-pathway intermediates for ligand binding. Taken together,
the interplay between fast internal motions, which are intimately related to
conformational entropy, and slow internal motions, which are related to poorly
populated conformational states, can regulate protein activity in a way that
cannot be predicted on the basis of the protein's ground-state structure.
PMID- 28510175
TI - The role of protein dynamics in allosteric effects-introduction.
PMID- 28510176
TI - Molecular mechanisms of acetylcholine receptor-lipid interactions: from model
membranes to human biology.
AB - Lipids are potent modulators of the Torpedo nicotinic acetylcholine receptor.
Lipids influence nicotinic receptor function by allosteric mechanisms,
stabilizing varying proportions of pre-existing resting, open, desensitized, and
uncoupled conformations. Recent structures reveal that lipids could alter
function by modulating transmembrane alpha-helix/alpha-helix packing, which in
turn could alter the conformation of the allosteric interface that links the
agonist-binding and transmembrane pore domains-this interface is essential in the
coupling of agonist binding to channel gating. We discuss potential mechanisms by
which lipids stabilize different conformational states in the context of the
hypothesis that lipid-nicotinic receptor interactions modulate receptor function
at biological synapses.
PMID- 28510177
TI - Review of biophysical factors affecting osteogenic differentiation of human adult
adipose-derived stem cells.
AB - Developing bone is subject to the control of a broad variety of influences in
vivo. For bone repair applications, in vitro osteogenic assays are routinely used
to test the responses of bone-forming cells to drugs, hormones, and biomaterials.
Results of these assays are used to predict the behavior of bone-forming cells in
vivo. Stem cell research has shown promise for enhancing bone repair. In vitro
osteogenic assays to test the bone-forming response of stem cells typically use
chemical solutions. Stem cell in vitro osteogenic assays often neglect important
biophysical cues, such as the forces associated with regular weight-bearing
exercise, which promote bone formation. Incorporating more biophysical cues that
promote bone formation would improve in vitro osteogenic assays for stem cells.
Improved in vitro osteogenic stimulation opens opportunities for "pre
conditioning" cells to differentiate towards the desired lineage. In this review,
we explore the role of select biophysical factors-growth surfaces, tensile
strain, fluid flow and electromagnetic stimulation-in promoting osteogenic
differentiation of stem cells from human adipose. Emphasis is placed on the
potential for physical microenvironment manipulation to translate tissue
engineering and stem cell research into widespread clinical usage.
PMID- 28510179
TI - Design and operation of an automated high-throughput monoclonal antibody
facility.
AB - Monoclonal antibodies now form a key part of the biochemist's toolbox, and are
important reagents for therapeutic applications. This has resulted in a need for
high-throughput production to satisfy the demand from the global community.
Manual production involves overwhelming amounts of tissue culture and associated
liquid handling steps to achieve high-throughput operation. By contrast,
automated systems can readily cope with the numbers required. In this review, we
address the development of automated systems, and discuss the pros and cons of
their operation.
PMID- 28510178
TI - SH3 domains: modules of protein-protein interactions.
AB - Src homology 3 (SH3) domains are involved in the regulation of important cellular
pathways, such as cell proliferation, migration and cytoskeletal modifications.
Recognition of polyproline and a number of noncanonical sequences by SH3 domains
has been extensively studied by crystallography, nuclear magnetic resonance and
other methods. High-affinity peptides that bind SH3 domains are used in drug
development as candidates for anticancer treatment. This review summarizes the
latest achievements in deciphering structural determinants of SH3 function.
PMID- 28510182
TI - Metal ion-dependent anti-termination of transcriptional regulation of
ribonucleoprotein complexes.
AB - Anti-terminator proteins are frequently used by bacteria to sense a specific
metabolite signal and direct RNA polymerase to either terminate or continue
transcription of the genes downstream of an operon. One such protein is HutP,
which binds to upstream cis-regulatory sequences to regulate expression of the
histidine utilization (hut) operon in Bacillus subtilis. HutP must be activated
by L-histidine and divalent metal ions before binding to hut mRNA; binding of
activated HutP prevents termination of transcription. Thus, HutP appears to
regulate the hut operon in a unique fashion in this class of regulatory proteins.
To understand gene (hut operon) regulation by HutP, we performed several
biochemical and structural studies. These studies reveal events in the regulatory
mechanism, starting with the activation of HutP and ending with the unwinding of
hut terminator RNA. In this review, we describe the unique regulatory mechanisms
commonly used by many Bacillus species.
PMID- 28510180
TI - Structural and mechanical functions of integrins.
AB - Integrins are ubiquitously expressed cell surface receptors that play a critical
role in regulating the interaction between a cell and its microenvironment to
control cell fate. These molecules are regulated either via their expression on
the cell surface or through a unique bidirectional signalling mechanism. However,
integrins are just the tip of the adhesome iceberg, initiating the assembly of a
large range of adaptor and signalling proteins that mediate the structural and
signalling functions of integrin. In this review, we summarise the structure of
integrins and mechanisms by which integrin activation is controlled. The
different adhesion structures formed by integrins are discussed, as well as the
mechanical and structural roles integrins play during cell migration. As the
function of integrin signalling can be quite varied based on cell type and
context, an in depth understanding of these processes will aid our understanding
of aberrant adhesion and migration, which is often associated with human
pathologies such as cancer.
PMID- 28510184
TI - Footprint of the eastern euroasian past in Italian populations of Cryptotaenia
thomasii (Ten.) DC.
AB - BACKGROUND: The knowledge of the genetic architecture of closely related species
and/or populations of a single species can be very useful to shed light on the
processes that led to their current distributions. The present study provides a
preliminary evaluation of the conservation status of the populations of
Cryptotaenia thomasii, a very narrow endemic species occurring in southern Italy.
Previous studies showed that C. thomasii was phylogenetically closely related to
C. flahaultii, endemic species of Caucasus, and to evaluate its conservation
status and the genetic variability of plant species the internal transcribed
spacers (ITSs) of nuclear ribosomal DNA were sequenced and the SNPs were
analyzed. RESULTS: The restriction analysis of nrDNA with the restriction enzymes
allowed to detect the presence of two single mutations (SNPs) among the sequences
of two species. Our molecular analysis pointed out that C. thomasii and C.
flahaultii, in spite of their geographical disjunction, show a sign of an ancient
contact as an extreme case of geographical disjunction Italian-Caucasus.
CONCLUSION: From the evolutionary history of the species and its distribution
pattern one can reconstruct a possible scenario with some hypotheses that explain
the hypothetical ancestral area where the two species were in contact. We
speculate the two species may have originated from fragmentation of a common
ancestor widespread in the Western Palearctic zone and have survived in two
separated refuge areas limited by important mountain systems. This hypothesis is
supported by our molecular analysis, in fact, the analysis of SNPs showed that
some C. thomasii populations retain the signs of an ancient link with C.
flahaultii.
PMID- 28510181
TI - Integrins in development and cancer.
AB - The correct control of cell fate decisions is critical for metazoan development
and tissue homeostasis. It is established that the integrin family of cell
surface receptors regulate cell fate by mediating cell-cell and cell
extracellular matrix (ECM) interactions. However, our understanding of how the
different family members control discrete aspects of cell biology, and how this
varies between tissues and is temporally regulated, is still in its infancy. An
emerging area of investigation aims to understand how integrins translate changes
in tension in the surrounding microenvironment into biological responses. This is
particularly pertinent due to changes in the mechanical properties of the ECM
having been linked to diseases, such as cancer. In this review, we provide an
overview of the roles integrins play in important developmental processes, such
as proliferation, polarity, apoptosis, differentiation and maintenance of
"stemness". We also discuss recent advances in integrin mechanobiology and
highlight the involvement of integrins and aberrant ECM in cancer.
PMID- 28510183
TI - CFTR and TNR-CFTR expression and function in the kidney.
AB - The cystic fibrosis transmembrane conductance regulator (CFTR) is abundantly
expressed in the kidney. CFTR mRNA is detected in all nephron segments of rats
and humans and its expression is higher in the renal cortex and outer medulla
than in the inner medulla. CFTR protein is detected at the apical surface of both
proximal and distal tubules of rat kidney but not in the outer medullary
collecting ducts. The localization of CFTR in the proximal tubules is compatible
with that of endosomes, suggesting that CFTR might regulate pH in endocytic
vesicles by equilibrating H+ accumulation due to H+-ATPase activity. Many studies
have also demonstrated that CFTR also regulates channel pore opening and the
transport of sodium, chloride and potassium. The kidneys also express a CFTR
splicing variant, called TNR-CFTR, in a tissue-specific manner, primarily in the
renal medulla. This splicing variant conserves the functional characteristics of
wild-type CFTR. The functional significance of TNR-CFTR remains to be elucidated,
but our group proposes that TNR-CFTR may have a basic function in intracellular
organelles, rather than in the plasma membrane. Also, this splicing variant is
able to partially substitute CFTR functions in the renal medulla of Cftr-/- mice
and CF patients. In this review we discuss the major functions that have been
proposed for CFTR and TNR-CFTR in the kidney.
PMID- 28510186
TI - Broomcorn and foxtail millet were cultivated in Taiwan about 5000 years ago.
AB - BACKGROUND: Archaeobotanical remains of millet were found at the Nan-kuan-li East
site in Tainan Science Park, southern Taiwan. This site, dated around 5000-4300
BP, is characterized by remains of the Tapenkeng culture, the earliest Neolithic
culture found so far in Taiwan. A large number of millet-like carbonized and
charred seeds with varied sizes and shapes were unearthed from the site by the
flotation method. Since no millet grain was ever found archaeologically in Taiwan
previously, this discovery is of great importance and significance. This paper is
in an attempt to further analyze these plant remains for a clearer understanding
of the agricultural practice of the ancient inhabitants of the Nan-kuan-li East
site. RESULT: We used light and scanning electron microscopy to examine the
morphological features of some modern domesticated and unearthed seeds to compare
and identify the archaeobotanical remains by three criteria: caryopsis shape,
embryo notch, and morphology of lemma and palea. We also developed a new
methodology for distinguishing the excavated foxtail and broomcorn millet seeds.
CONCLUSION: Two domesticated millet, including broomcorn millet (Panicum
miliaceum) and foxtail millet (Setaria italica), as well as one wild millet
species, yellow foxtail (Setaria glauca), were identified in the unearthed seeds.
Together with the millet remains, rice was also cultivated in the area.
Archaeological evidence shows that millet and rice farming may have been
important food sources for people living about 5000 years ago in southern Taiwan.
PMID- 28510185
TI - Morphological, physiological, cytological and phytochemical studies in diploid
and colchicine-induced tetraploid plants of Fagopyrum tataricum (L.) Gaertn.
AB - BACKGROUND: Tartary buckwheat are very popular as an important functional food
material and its cultivation is very widespread in our whole world, but there
obviously lack works in the researches of genetic breeding for agricultural and
medicinal utilization. The aim of this study is to obtain good germplasm
resources for agricultural and medicinal use of tartary buckwheat (Fagopyrum
tataricum) by inducing the tetraploid plants. RESULTS: Four cultivars of F.
tataricum, that is, Qianwei 2#, Jinku 2#, Chuanqiao 1#, and Liuqiao 1# were
selected to experiment. The tips of seedlings with two true leaves were treated
by 0.25% (w/v) colchicine solution for 48, 72, and 96 h, respectively. The
chromosome number of treated plants was determined by metaphase chromosome
counting of root tip cells and PMCs (pollen mother cells) meiosis observation.
Tetraploid induction successfully occurred in all three treatments with an
efficiency ranging from 12.13 to 54.55%. The chromosome number of the diploid
plants was 2n = 2x = 16, and that of the induced tetraploid plants was 2n = 4x =
32. The typical morphological and physiological qualities were compared between
the control diploid and corresponding induced tetraploid plants. Results showed
that the induced tetraploid plants had obviously larger leaves, flowers, and
seeds. Moreover, the content of seed protein and flavonoid were also increased in
the tetraploid plants. The pollen diameter and capsule size of diploid plants
were significantly smaller than those of tetraploid plants. CONCLUSION: Fagopyrum
tataricum can be effectively induced into tetraploids by colchicines. The
tetraploid induction can produce valuable germplasm resources for breeding and is
a practicable breeding way in F. tataricum.
PMID- 28510187
TI - Identification and trichothecene genotypes of Fusarium graminearum species
complex from wheat in Taiwan.
AB - BACKGROUND: Fusarium head blight (FHB) of wheat caused by Fusarium graminearum
species complex (FGSC) is a devastating disease worldwide. The pathogens not only
reduce the yield of wheat, but also impact the quality of wheat by contamination
with trichothecene mycotoxins. A systematic investigation on the pathogens of FHB
in Taiwan is lacking. Here, molecular and morphological approaches were used to
identify species of the Taiwanese FGSC isolates and determine their trichothecene
genotypes. RESULTS: In this study, a total of 195 isolates of FGSC from diseased
wheat were collected from 8 areas of northern and central Taiwan. All isolates
were subjected to seedling inoculation for verification of pathogenicity. The
pathogenic isolates were genetically characterized by sequence characterized
amplified region (SCAR), PCR- restriction fragment length polymorphism (RFLP),
phylogenetic analysis and fixed nucleotides to clarify their phylogenetic
species, and by PCR assays of TRI genes to determine trichothecene genotypes.
They were identified as F. asiaticum, F. graminearum sensu stricto, F.
meridionale and an unknown species. Isolates of F. asiaticum were the major
causal agents (98%) in this investigated population and were comprised of SCAR
type 5 (75%), SCAR type 4 (21%) and SCAR type 3 (2%). Their trichothecene
genotypes were either 15-acetyl-deoxynivalenol (15-ADON) (83%) or nivalenol (NIV)
genotype (17%). These genetic characterizations indicated that F. asiaticum (15
ADON SCAR type 5) accounts for 60% of this Taiwanese population. Virulence assay
on wheat heads indicated virulence of F. asiaticum isolates in subpopulations
divided by SCAR types or trichothecene genotypes were comparable, suggesting
other factors influence the unequal subpopulation sizes. CONCLUSIONS: This is the
first study that FGSC isolates in Taiwan were systematically collected and
characterized. In addition to F. graminearum sensu stricto and F. meridionale, F.
asiaticum with 15-ADON genotype was identified as the predominate species in
Taiwan. In contrast to Chinese and Japanese populations that F. asiaticum
isolates were typically of 3-ADON or NIV genotype, the predominate 15-ADON
genotype in Taiwanese population was unique among F. asiaticum populations and
represented the southernmost 15-ADON genotype population in East Asia.
PMID- 28510188
TI - Mitigation of salt stress in white clover (Trifolium repens) by Azospirillum
brasilense and its inoculation effect.
AB - BACKGROUND: Salinity is one of the increasingly serious environmental problems
worldwide for cultivating agricultural crops. The present study was aimed to
ascertain the potential of beneficial soil bacterium Azospirillum brasilense to
alleviate saline stress in Trifolium repens. Experimental plants (white clover)
were grown from seeds and inoculated with or without A. brasilense bacterial
strain supplemented with 0, 40, 80, or 120 mM NaCl into soil. RESULTS: The growth
attributes including, shoot heights, root lengths, fresh and dry weights, leaf
area and chlorophyll content were significantly enhanced in T. repens plants
grown in A. brasilense inoculated soil than un-inoculated controls, particularly
under elevated salinity conditions (40, 80 and 120 mM NaCl). Malondialdehyde
content of leaf was recorded to be declined under saline conditions. Moreover,
the K+/Na+ ratio was also improved in bacterium-inoculated plants, since A.
brasilense significantly reduced the root and shoot Na+ level under high salty
environment. CONCLUSIONS: Results revealed that soil inoculation with A.
brasilense could significantly promote T. repens growth under both non-saline and
saline environments, and this study might be extended to other vegetables and
crops for the germination and growth enhancement.
PMID- 28510190
TI - Chilling susceptibility in mungbean varieties is associated with their
differentially expressed genes.
AB - BACKGROUND: Mungbean (Vigna radiata L. Wilczek) is an economically important
legume of high nutritional value, however, its cultivation is limited by
susceptibility to chilling. Varieties NM94 and VC1973A, with differential
susceptibility to stress, serve as good materials for uncovering how they differ
in chilling tolerance. This study aimed to identify the ultrastructural,
physiological and molecular changes to provide new insights on the differential
susceptibility to chilling between varieties VC1973A and NM94. RESULTS: Chilling
stress caused a greater reduction in relative growth rate, a more significant
decrease in maximum photochemical efficiency of PSII and DPPH scavenging activity
and more-pronounced ultrastructural changes in VC1973A than in NM94 seedlings.
Comparative analyses of transcriptional profiles in NM94 and VC1973A revealed
that the higher expression of chilling regulated genes (CORs) in NM94. The
transcript levels of lipid transfer protein (LTP), dehydrin (DHN) and plant
defensin (PDF) in NM94 seedlings after 72 h at 4 degrees C was higher than that
in its parental lines VC1973A, 6601 and VC2768A. CONCLUSIONS: Our results
suggested that LTP, DHN and PDF may mediate chilling tolerance in NM94 seedlings.
PMID- 28510189
TI - Multiple regulatory roles of AP2/ERF transcription factor in angiosperm.
AB - APETALA2/ethylene response factor (AP2/ERF) transcription factor (TF) is a
superfamily in plant kingdom, which has been reported to be involved in
regulation of plant growth and development, fruit ripening, defense response, and
metabolism. As the final response gene in ethylene signaling pathway, AP2/ERF TF
could feedback modulate phytohormone biosynthesis, including ethylene, cytokinin,
gibberellin, and abscisic acid. Moreover, AP2/ERF TF also participates in
response to the signals of auxin, cytokinin, abscisic acid, and jasmonate. Thus,
this superfamily is key regulator for connecting the phytohormonal signals. In
this review, based on the evidence of structural and functional studies, we
discussed the multiple regulator roles of AP2/ERF TF in angiosperm, and then
constructed the network model of AP2/ERF TF in response to various phytohormonal
signals and regulatory mechanism of the cross-talk.
PMID- 28510192
TI - Phellinus noxius: molecular diversity among isolates from Taiwan and its
phylogenetic relationship with other species of Phellinus based on sequences of
the ITS region.
AB - BACKGROUND: Analysis of phylogenetic relationship of 91 isolates of Phellinus
noxius obtained from 46 plant species in Taiwan did not show distinct grouping
based on ITS sequences. RESULTS: However, the ITS nucleotides showed 20 different
kinds of variations including single nucleotide polymorphisms, deletion and
insertion in ITS1 and ITS2, but none in 5.8 S. The Taiwanese isolates of P.
noxius were dividable into long (type L), median (type M) and short (type S)
groups based on ITS sequence length. Two isolates with identical ITS sequence
belonged to types L. Type M with 72 isolates was further divided into 33
subtypes, while types S with 17 isolates was further divided into two subtypes.
CONCLUSION: Phylogenetic analysis of ITS sequences among Phellinus species showed
that isolates of P. noxius were in the same clade distinctly separated from other
Phellinus species.
PMID- 28510191
TI - Taxonomy of Cyrtochilum-alliance (Orchidaceae) in the light of molecular and
morphological data.
AB - BACKGROUND: The generic separateness and specific composition of the orchid genus
Cyrtochilum was discussed for almost two centuries. Over the years several
smaller taxa were segregated from this taxon, but their separateness was recently
questioned based on molecular studies outcomes. The aim of our study was to
revise concepts of morphological-based generic delimitation in Cyrtochilum
alliance and to compare it with the results of genetic analysis. We used
phylogenetic framework in combination with phenetical analysis to provide
proposal of the generic delimitation within Cyrtochilum-alliance. Two molecular
markers, ITS and matK were used to construct phylogenetic tree. A total of over
5000 herbarium specimens were included in the morphological examination and the
phenetical analysis included 29 generative and vegetative characters. RESULTS:
Comparative morphology of the previously recognized genera: Buesiella,
Dasyglossum, Neodryas, Rusbyella, Siederella and Trigonochilum is presented. A
new species within the the latter genus is described. Fourteen new combinations
are proposed. The key to the identification of the genera of the Cyrtochilum
alliance and morphological characteristics of each genus are provided.
CONCLUSIONS: A total of six separated genera are recognized within Cyrtochilum
alliance. The reasons of the incompatibility between morphological differences
observed within studied taxa and phylogenetic tree are argued and the taxonomic
implications of such inconsistency, resulting in fragmentation or lumping of
taxonomic units, are discussed.
PMID- 28510193
TI - Characterization of LhSorP5CS, a gene catalyzing proline synthesis in Oriental
hybrid lily Sorbonne: molecular modelling and expression analysis.
AB - BACKGROUND: Abiotic stresses negatively affect plant growth and flower
production. In plants, P5CS proteins are key enzymes that catalyzed the rate
limiting steps of proline synthesis, and proline is a well-known osmoprotectant
that is closely related to abiotic stress tolerance. However, information about
the P5CS genes, their effects on proline accumulation, and their role in abiotic
stress tolerance in Lilium is still lacking. RESULTS: We isolated and
characterized a novel gene (LhSorP5CS) from Oriental hybrid lily cultivar
Sorbonne. Phylogenetic analysis indicated that LhSorP5CS is a member of the P5CS
family. The three-dimensional structure of LhSorP5CS predicted by homology
modeling showed high similarity to its correspondant human P5CS template. Further
gene expression analysis revealed that LhSorP5CS expression was up-regulated by
NaCl, mannitol, and ABA, and that stress-exposed plants accumulated proline at a
significantly higher level than in the control. CONCLUSIONS: LhSorP5CS
characterized in this study is involved in proline synthesis in lily, and that it
might play an important role in abiotic stress tolerance. However, there should
be other P5CS homologues in the lily genome, and some of them could be highly
stress-induced and more important for proline accumulation. Future studies on
P5CS family genes would be of great importance to proline-related stress
tolerance in lily.
PMID- 28510194
TI - Molecular recircumscription of Broussonetia (Moraceae) and the identity and
taxonomic status of B. kaempferi var. australis.
AB - BACKGROUND: Despite being a relatively small genus, the taxonomy of the paper
mulberry genus Broussonetia remains problematic. Much of the controversy is
related to the identity and taxonomic status of Broussonetia kaempferi var.
australis, a name treated as a synonym in the floras of Taiwan and yet accepted
in the floras of China. At the generic level, the monophyly of Corner (Gard Bull
Singap 19:187-252, 1962)'s concept of Broussonetia has not been tested. In recent
studies of Broussonetia of Japan, lectotypes of the genus were designated and
three species (B. kaempferi, Broussonetia monoica, and Broussonetia papyrifera)
and a hybrid (B. *kazinoki) were recognized. Based on the revision and molecular
phylogenetic analyses, this article aims to clarify these issues. RESULTS:
Herbarium studies, field work, and molecular phylogenetic analyses indicate that
all Taiwanese materials identifiable to B. kaempferi var. australis are
conspecific with B. monoica of Japan and China. Molecular phylogenetic analyses
showed that Broussonetia sensu Corner (Gard Bull Singap 19:187-252, 1962)
contains two clades corresponding to sect. Broussonetia and sect. Allaeanthus,
with Malaisia scandens sister to sect. Broussonetia. CONCLUSIONS: Based on our
analyses, B. kaempferi var. australis is treated as a synonym of B. monoica and
that B. kaempferi is not distributed in Taiwan. To correct the non-monophyly of
Broussonetia sensu Corner (Gard Bull Singap 19:187-252, 1962), Broussonetia is
recircumscribed to contain only sect. Broussonetia and the generic status of
Allaeanthus is reinstated.
PMID- 28510195
TI - Meso- or xeromorphic? Foliar characters of Asteraceae in a xeric scrub of Mexico.
AB - BACKGROUND: The anatomical traits associated with water deficit are also observed
in plants growing in poor soils. The species may resist water deficit through
three main strategies: escape, avoid or tolerate. The Pedregal de San Angel
Ecological Reserve (REPSA), Mexico, is an environment with low nutrient soil and
low water availability. It is set on the basalt formation derived from the Xitle
volcano eruption. The main vegetation type is characterized as xerophytic shrub.
Thus we expect that species growing in this community will show leaf xeromorphic
traits and may have any of the three response strategies. We analyzed the foliar
anatomy of 52 species of the Asteraceae family at the REPSA because it is the
most abundant angiosperm family in the site, showing a wide variety of growth
forms and anatomical variation. RESULTS: The foliar anatomies of the studied
Asteraceae were highly variable as well as their quantitative traits as revealed
by principal component analysis. This agrees with previous studies that found
great anatomical variation within the family. Leaves have multiple layered
palisade parenchyma and parenchyma bundle sheaths and could not be categorized as
xeromorphic because they possess mesomorphic leaf features as simple lamina,
single-layered epidermis, and soft large-size glabrous leaves with high specific
leaf area. CONCLUSIONS: The combination of mesomorphic and few xeromorphic foliar
traits with other characters at the genus and tribal level probably has been
essential in Asteraceae to colonize various environments, including those with
low water and nutrient availability.
PMID- 28510196
TI - Anti-fungal activity, mechanism studies on alpha-Phellandrene and Nonanal against
Penicillium cyclopium.
AB - BACKGROUND: Essential oils from plants have been reported to have wide spread
antimicrobial activity against various bacterial and fungal pathogens, and these
include alpha-Phellandrene, Nonanal and other volatile substances. However,
biological activities of alpha-Phellandrene and Nonanal have been reported only
in a few publications. Further investigations are necessary to determine the
antimicrobial activity of these compounds, especially for individual application,
to establish the possible mechanism of action of the most active compound.
RESULTS: The results are shown that alpha-Phellandrene and Nonanal have a dose
dependent inhibition on the mycelial growth of Penicillium cyclopium. The minimum
inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) are 1.7
and 1.8 mL/L for alpha-Phellandrene, 0.3 and 0.4 mL/L for Nonanal, respectively.
The volatile compounds altered the morphology of P. cyclopium hyphae by causing
loss of cytoplasmic material and distortion of the mycelia. The membrane
permeability of P. cyclopium increased with increasing concentrations of the two
volatile compounds, as evidenced by cell constituent release, extracellular
conductivity and induced efflux of K+. Moreover, the two volatile compounds
induced a decrease in pH and in the total lipid content of P. cyclopium, which
suggested that cell membrane integrity had been compromised. CONCLUSIONS: The
results demonstrated that alpha-Phellandrene and Nonanal could significantly
inhibit the mycelia growth of P. cyclopium by severely disrupting the integrity
of the fungal cell membrane, leading to the leakage of cell constituents and
potassium ions, and triggering an increase of the total lipid content,
extracellular pH and membrane permeability. Our present study suggests that alpha
Phellandrene and Nonanal might be a biological fungicide for the control of P.
cyclopium in postharvest tomato fruits.
PMID- 28510197
TI - Assimilates mobilization, stable canopy temperature and expression of expansin
stabilizes grain weight in wheat cultivar LOK-1 under different soil moisture
conditions.
AB - BACKGROUND: Grain yield of wheat is primarily determined by both grain number and
grain weight, which often influence each other in response to environmental
stimuli. Some of the genotypes are capable of maintaining high single grain
weight (SGW) across the environments. Understanding mechanisms and factors
associated with the superiority of such genotypes over others is necessary to
enhance productivity of wheat. RESULTS: Experiments were conducted to elucidate
the physiological basis of high SGW of LOK-1, a wheat cultivar grown in dry and
hot environments in the central and peninsular zones of India. SGW of LOK-1 was
least affected by removal of spikelets indicating little competition between the
grains within the spike for assimilates. Reduction in SGW due to defoliation was
less and the contribution of stem reserves to the grain development was high in
LOK-1 relative to other cultivars. It seems that high level of expression of
genes such as expansin (TaExpA6) contributes to the high SGW of LOK-1.
CONCLUSIONS: Source was not a limiting factor for grain growth of LOK-1 in
contrast to other cultivars, whereas sink appeared to be a limiting factor in
recently released/identified cultivars. Differences in the amounts of water
soluble stem carbohydrate reserves translocated to grain could be one of the
factors contributing to higher grain weight in LOK-1. High level expression of
TaExpA6, one of the genes contributing to the elongation of endosperm, seems to
be crucial for grain growth in wheat.
PMID- 28510198
TI - Investigation of floristic similarities between Taiwan and terrestrial ecoregions
in Asia using GBIF data.
AB - BACKGROUND: Floristic compositions of non-endemic plants of continental islands
were related to the neighboring continents because non-endemic plant species had
historically migrated to continental islands from source areas. This study
attempts to identify source areas of a continental island by means of floristic
analysis and to assess possible migration routes on the basis of geographical
distribution ranges of plants. Large quantities of angiosperm data records were
downloaded from the Global Biodiversity Information Facility (GBIF). Similarity
index and cluster analysis were used to identify the floristic similarities among
22 geographical localities of Taiwan (GLTs) and 34 terrestrial ecoregions in
Asia. Geographical distribution ranges of non-endemic angiosperm species in
Taiwan (NEASTs) were evaluated to mirror the possible migration routes from
different source areas to Taiwan. RESULTS: There are 3275 angiosperm species in
Taiwan derived from the dataset of GBIF. Among them, 847 are endemic and 2428 are
NEASTs. Geographical distribution ranges of the 2428 NEASTs were categorized into
7 distribution groups. They were widely distribution from equator to Siberia (27
species), tropical ecoregions (345 species), tropical and subtropical ecoregions
(663 species), tropical to temperate ecoregions (591 species), subtropical
ecoregions (265 species), subtropical to temperate ecoregions (387 species), and
temperate ecoregions (150 species). Results of similarity indices and cluster
analysis demonstrated that high floristic similarities were observed among GLTs
at lowland and southern Taiwan and tropical and subtropical ecoregions in Asia.
GLTs at high mountains were assumed to have floristic similarity with temperate
ecoregions in Asia, whereas the assumption was not supported by our analysis. It
is partly because of that angiosperms with tropical and subtropical distributions
extend their ranges from low to high elevations in Taiwan. CONCLUSIONS:
Subtropical ecoregions at southern China and tropical ecoregions at Indochina
were more important than temperate ecoregions on playing source areas of NEASTs.
Geographical distribution ranges of NEASTs implied that most of the NEASTs were
probably migrated from topical or subtropical ecoregions of Asian continent to
Taiwan.
PMID- 28510199
TI - Taxonomic placement of Paphiopedilum rungsuriyanum (Cypripedioideae; Orchidaceae)
based on morphological, cytological and molecular analyses.
AB - BACKGROUND: Paphiopedilum rungsuriyanum from Northern Laos was discovered and
described in 2014. It is characterized by having miniature tessellated leaves, a
flower having a helmet shaped lip with a V-shaped neckline, and a semi-lunate, 3
dentate staminode with an umbo. These morphological features distinguish P.
rungsuriyanum from the other known sections/subgenera of Paphiopedilum, making it
difficult to group with existing infrageneric units. RESULTS: Paphiopedilum
rungsuriyanum has chromosome number of 2n = 26. Fluorescence in situ
hybridization study demonstrates that there are two 45S rDNA signals in the
telomeric region of chromosomes, and more than 20 5S rDNA signals dispersed
signals in the pericentromeric and centromeric regions. Phylogenetic analyses
based on four nuclear (i.e. ITS, ACO, DEF4 and RAD51) and four plastid (i.e. atpI
atpH, matK, trnS-trnfM and ycf1) gene regions indicate that P. rungsuriyanum is
nested in subgenus Paphiopedilum and is a sister to section Paphiopedilum.
CONCLUSIONS: The results in combination with karyomorphological, rDNA FISH
patterns, morphological and phylogenetic analyses suggest a new section Laosianum
to accommodate this species in the current sectional circumscription of subgenus
Paphiopedilum.
PMID- 28510200
TI - Cambial variations of Piper (Piperaceae) in Taiwan.
AB - BACKGROUND: Cambial variations in lianas of Piperaceae in Taiwan have not been
studied previously. The stem anatomy of seven Piper species from Taiwan was
examined to document cambial variations and better distinguish the species when
leaves are absent. RESULTS: A key for the seven species is provided, based on the
internal stem anatomy. The seven Piper species climb via adventitious roots, and
in cross section, the stems were generally eccentric and oblate, although a
transversely elliptic stem was found in P. kadsura (Choisy) Ohwi and P.
sintenense Hatus. A cambial variant with secondary growth of external primary
vascular bundles and xylem in plates was observed in all species except Piper
betle L., which developed another cambium variant with xylem furrowed deeply by
parenchyma proliferation. The sclerenchymatous ring surrounding the medullary
vascular bundles was always continuous except in P. betle, where it was
discontinuous. Mucilage canals varied from absent to present in the center of the
pith, or present in the pith and inner cortex. Different sizes of vessels
dispersed throughout the stem were ring or diffuse porous. The numbers of
medullary and peripheral vascular bundles were distinctive and the widths of rays
were noticeably different in each species. Differences in the growth rate of the
medullary vascular bundles produced two development types of vascular bundles,
although in both types, the peripheral vascular bundles gradually lengthen and
become separated from each other by wide rays. CONCLUSIONS: We documented the
internal stem anatomy of six previously unstudied species of Piper, including
three endemic species, P. kwashoense Hayata, P. sintenense, and P. taiwanense Lin
and Lu, and found that P. betle had deeply furrowed xylem, which had not been
reported for the species before. The descriptions and photographs of seven Piper
species will also provide a basis for further morphological studies.
PMID- 28510201
TI - Ultramafic geoecology of South and Southeast Asia.
AB - Globally, ultramafic outcrops are renowned for hosting floras with high levels of
endemism, including plants with specialised adaptations such as nickel or
manganese hyperaccumulation. Soils derived from ultramafic regoliths are
generally nutrient-deficient, have major cation imbalances, and have concomitant
high concentrations of potentially phytotoxic trace elements, especially nickel.
The South and Southeast Asian region has the largest surface occurrences of
ultramafic regoliths in the world, but the geoecology of these outcrops is still
poorly studied despite severe conservation threats. Due to the paucity of
systematic plant collections in many areas and the lack of georeferenced
herbarium records and databased information, it is not possible to determine the
distribution of species, levels of endemism, and the species most threatened.
However, site-specific studies provide insights to the ultramafic geoecology of
several locations in South and Southeast Asia. The geoecology of tropical
ultramafic regions differs substantially from those in temperate regions in that
the vegetation at lower elevations is generally tall forest with relatively low
levels of endemism. On ultramafic mountaintops, where the combined forces of
edaphic and climatic factors intersect, obligate ultramafic species and
hyperendemics often occur. Forest clearing, agricultural development, mining, and
climate change-related stressors have contributed to rapid and unprecedented loss
of ultramafic-associated habitats in the region. The geoecology of the large
ultramafic outcrops of Indonesia's Sulawesi, Obi and Halmahera, and many other
smaller outcrops in South and Southeast Asia, remains largely unexplored, and
should be prioritised for study and conservation.
PMID- 28510202
TI - Small agarics in Taiwan: Mycena albopilosa sp. nov. and Gloiocephala epiphylla.
AB - BACKGROUND: Small agarics are poorly documented in Taiwan, with previously
reported species either rudimentarily described or lacking a description or
diagnosis in most cases. A survey on small agarics in a lowland forest of Taiwan
revealed two species previously unrecorded. RESULTS: One agaric, which is
characterized mainly by white hairs overlying the pileus, a conspicuous cup
shaped basal disc surrounding the stipe, and inamyloid basidiospores, fits the
genus Mycena and appears undescribed. It readily produced abundant basidiomata in
culture in three weeks. The other agaric is Gloiocephala epiphylla, being
characterized by its reduced hymenium and conspicuous pileogloeocystidia. ITS
sequences from the two agarics further corroborated the identifications. Their
macroscopic and microscopic features and culture morphology are described. A
dichotomous key is provided to the species of Mycena reported in Taiwan.
CONCLUSION: The Mycena species is newly described as M. albopilosa herein.
Gloiocephala epiphylla is new to Taiwan, being the only species of the genus
known on the island.
PMID- 28510203
TI - Begonia myanmarica (Begoniaceae), a new species from Myanmar, and molecular
phylogenetics of Begonia sect. Monopteron.
AB - BACKGROUND: A new species, Begonia myanmarica, was discovered from Myanmar and
herein documented. Characterized by a single developed wing in the ovary/fruit,
this species would be assigned to sect. Monopteron (sensu Doorenbos et al. in The
sections of Begonia including descriptions, keys and species lists: studies in
Begoniaceae VI. Wageningen Agricultural University, Wageningen, 1998) that is
known by B. griffithiana and B. nepalensis from the Himalaya. To confirm its
sectional assignment, we conducted morphological, phylogenetic and cytological
studies. RESULTS: Morphological observations indicated that B. myanmarica was
distinguishable from the two known species of sect. Monopteron by the leaf shape
and size, 1-locular ovary, parietal placentation and chromosome number. Molecular
phylogenetic analysis using nrITS sequences showed that B. myanmarica was not
allied with the clade of sect. Monopteron, though both were nested within sect.
Platycentrum-sect. Sphenanthera clade. CONCLUSIONS: Studies of morphology,
molecular phylogenetics and cytology support the recognition of the new species,
Begonia myanmarica, which is fully described and illustrated. Our results also
indicate that B. myanmarica is not closely related to species previously assigned
to sect. Monopteron, suggesting that the fruit morphology of a single developed
wing in the ovary/fruit characterizing sect. Monopteron is homoplasious.
PMID- 28510204
TI - Microarray meta-analysis to explore abiotic stress-specific gene expression
patterns in Arabidopsis.
AB - BACKGROUND: Abiotic stresses are the major limiting factors that affect plant
growth, development, yield and final quality. Deciphering the underlying
mechanisms of plants' adaptations to stresses using few datasets might overlook
the different aspects of stress tolerance in plants, which might be
simultaneously and consequently operated in the system. Fortunately, the
accumulated microarray expression data offer an opportunity to infer abiotic
stress-specific gene expression patterns through meta-analysis. In this study, we
propose to combine microarray gene expression data under control, cold, drought,
heat, and salt conditions and determined modules (gene sets) of genes highly
associated with each other according to the observed expression data. RESULTS: By
analyzing the expression variations of the Eigen genes from different conditions,
we had identified two, three, and five gene modules as cold-, heat-, and salt
specific modules, respectively. Most of the cold- or heat-specific modules were
differentially expressed to a particular degree in shoot samples, while most of
the salt-specific modules were differentially expressed to a particular degree in
root samples. A gene ontology (GO) analysis on the stress-specific modules
suggested that the gene modules exclusively enriched stress-related GO terms and
that different genes under the same GO terms may be alternatively disturbed in
different conditions. The gene regulatory events for two genes, DREB1A and DEAR1,
in the cold-specific gene module had also been validated, as evidenced through
the literature search. CONCLUSIONS: Our protocols study the specificity of the
gene modules that were specifically activated under a particular type of abiotic
stress. The biplot can also assist to visualize the stress-specific gene modules.
In conclusion, our approach has the potential to further elucidate mechanisms in
plants and beneficial for future experiments design under different abiotic
stresses.
PMID- 28510205
TI - The lipid network.
AB - Natural cell membranes are composed of a remarkable variety of lipids, which
provide specific biophysical properties to support membrane protein function. An
improved understanding of this complexity of membrane composition may also allow
the design of membrane active drugs. Crafting a relevant model of a cell membrane
with controlled composition is becoming an art, with the ability to reveal the
molecular mechanisms of biological processes and lead to better treatment of
pathologies. By matching physiological observations from in vivo experiments to
high-resolution information, more easily obtained from in vitro studies, complex
interactions at the lipid interface are determined. The role of the lipid network
in biological membranes is, therefore, the subject of increasing attention.
PMID- 28510206
TI - Contributions of fluorescence techniques to understanding G protein-coupled
receptor dimerisation.
AB - G protein-coupled receptors (GPCRs) are the largest class of eukaryotic cell
surface receptors and, over the last decade, it has become clear that they are
capable of dimerisation. Whilst many biochemical and biophysical approaches have
been used to study dimerisation, fluorescence techniques, including Forster
resonance energy transfer and single molecule fluorescence, have been key
players. Here we review recent contributions of fluorescence techniques to
investigate GPCR dimers, including dimerisation in cell membranes and native
tissues, the effect of ligand binding on dimerisation and the kinetics of dimer
formation and dissociation. The challenges of studying multicomponent membrane
protein systems have led to the development and refinement of many fluorescence
assays, allowing the functional consequences of receptor dimerisation to be
investigated and individual protein molecules to be imaged in the membranes of
living cells. It is likely that the fluorescence techniques described here will
be of use for investigating many other multicomponent membrane protein systems.
PMID- 28510207
TI - Gold nanoclusters as novel optical probes for in vitro and in vivo fluorescence
imaging.
AB - Fluorescent probes play an important role in the development of fluorescence
based imaging techniques for life sciences research. Gold nanoclusters (AuNCs)
are a novel type of fluorescent nanomaterials which have attracted great interest
in recent years. Composed of only a few atoms, these ultrasmall AuNCs exhibit
quantum confinement effects and molecule-like properties. Fluorescent AuNCs have
an attractive set of features including ultrasmall size, good biocompatibility
and photostability, and tunable emission in the red to near-infrared spectral
region, which make them promising as fluorescent labels for biological imaging.
Examples of their application include live cell labeling, cancer cell targeting,
cellular apoptosis monitoring, and in vivo tumor imaging. Here, we present a
brief overview of recent advances in utilizing these emissive ultrasmall AuNCs as
optical probes for in vitro and in vivo fluorescence imaging.
PMID- 28510208
TI - Mesoscopic analysis of motion and conformation of cross-bridges.
AB - The orientation of a cross-bridge is widely used as a parameter in determining
the state of muscle. The conventional measurements of orientation, such as that
made by wide-field fluorescence microscopy, electron paramagnetic resonance (EPR)
or X-ray diffraction or scattering, report the average orientation of 1012-109
myosin cross-bridges. Under conditions where all the cross-bridges are immobile
and assume the same orientation, for example in normal skeletal muscle in rigor,
it is possible to determine the average orientation from such global
measurements. But in actively contracting muscle, where a parameter indicating
orientation fluctuates in time, the measurements of the average value provide no
information about cross-bridge kinetics. To avoid problems associated with
averaging information from trillions of cross-bridges, it is necessary to
decrease the number of observed cross-bridges to a mesoscopic value (i.e. the
value affected by fluctuations around the average). In such mesoscopic regimes,
the averaging of the signal is minimal and dynamic behavior can be examined in
great detail. Examples of mesoscopic analysis on skeletal and cardiac muscle are
provided.
PMID- 28510209
TI - Nonlinear optical microscopy in decoding arterial diseases.
AB - Pathological understanding of arterial diseases is mainly attributable to
histological observations based on conventional tissue staining protocols. The
emerging development of nonlinear optical microscopy (NLOM), particularly in
second-harmonic generation, two-photon excited fluorescence and coherent Raman
scattering, provides a new venue to visualize pathological changes in the
extracellular matrix caused by atherosclerosis progression. These techniques in
general require minimal tissue preparation and offer rapid three-dimensional
imaging. The capability of label-free microscopic imaging enables disease impact
to be studied directly on the bulk artery tissue, thus minimally perturbing the
sample. In this review, we look at recent progress in applications related to
arterial disease imaging using various forms of NLOM.
PMID- 28510210
TI - Brain connectivity during encoding and retrieval of spatial information:
individual differences in navigation skills.
AB - Emerging evidence suggests that the variations in the ability to navigate through
any real or virtual environment are accompanied by distinct underlying cortical
activations in multiple regions of the brain. These activations may appear due to
the use of different frame of reference (FOR) for representing an environment.
The present study investigated the brain dynamics in the good and bad navigators
using Graph Theoretical analysis applied to low-density electroencephalography
(EEG) data. Individual navigation skills were rated according to the performance
in a virtual reality (VR)-based navigation task and the effect of navigator's
proclivity towards a particular FOR on the navigation performance was explored.
Participants were introduced to a novel virtual environment that they learned
from a first-person or an aerial perspective and were subsequently assessed on
the basis of efficiency with which they learnt and recalled. The graph
theoretical parameters, path length (PL), global efficiency (GE), and clustering
coefficient (CC) were computed for the functional connectivity network in the
theta and alpha frequency bands. During acquisition of the spatial information,
good navigators were distinguished by a lower degree of dispersion in the
functional connectivity compared to the bad navigators. Within the groups of good
and bad navigators, better performers were characterised by the formation of
multiple hubs at various sites and the percentage of connectivity or small world
index. The proclivity towards a specific FOR during exploration of a new
environment was not found to have any bearing on the spatial learning. These
findings may have wider implications for how the functional connectivity in the
good and bad navigators differs during spatial information acquisition and
retrieval in the domains of rescue operations and defence systems.
PMID- 28510211
TI - Insights into genome architecture deduced from the properties of short Lac
repressor-mediated DNA loops.
AB - Genomic DNA is vastly longer than the space allotted to it in a cell. The
molecule must fold with a level of organization that satisfies the imposed
spatial constraints as well as allow for the processing of genetic information.
Key players in this organization include the negative supercoiling of DNA, which
facilitates the unwinding of the double-helical molecule, and the associations of
DNA with proteins, which partition the DNA into isolated loops, or domains. In
order to gain insight into the principles of genome organization and to visualize
the folding of spatially constrained DNA, we have developed new computational
methods to identify the preferred three-dimensional pathways of protein-mediated
DNA loops and to characterize the topological properties of these structures.
Here, we focus on the levels of supercoiling and the spatial arrangements of DNA
in model nucleoprotein systems with two topological domains. We construct these
systems by anchoring DNA loops in opposing orientations on a common protein-DNA
assembly, namely the Lac repressor protein with two bound DNA operators. The
linked pieces of DNA form a covalently closed circle such that the protein
attaches to two widely spaced sites along the DNA. We examine the effects of
operator spacing, loop orientation, and long-range contacts on overall chain
configuration and topology, and discuss our findings in the context of classic
experiments on the effects of supercoiling and operator spacing on Lac repressor
mediated looping and recent work on the role of proteins as barriers that divide
genomes into independent topological domains.
PMID- 28510213
TI - The emerging role of DNA supercoiling as a dynamic player in genomic structure
and function.
AB - This editorial highlights the pervasive role of DNA supercoiling in genomic
structure and function and introduces the main themes of the reviews in this
Special Issue.
PMID- 28510214
TI - Biophysical Reviews publications on DNA structure and function that complement
this Special Issue on DNA supercoiling.
PMID- 28510212
TI - Supercoiling biases the formation of loops involved in gene regulation.
AB - The function of DNA as a repository of genetic information is well-known. The
post-genomic effort is to understand how this information-containing filament is
chaperoned to manage its compaction and topological states. Indeed, the
activities of enzymes that transcribe, replicate, or repair DNA are regulated to
a large degree by access. Proteins that act at a distance along the filament by
binding at one site and contacting another site, perhaps as part of a bigger
complex, create loops that constitute topological domains and influence
regulation. DNA loops and plectonemes are not necessarily spontaneous, especially
large loops under tension for which high energy is required to bring their ends
together, or small loops that require accessory proteins to facilitate DNA
bending. However, the torsion in stiff filaments such as DNA dramatically
modulates the topology, driving it from extended and genetically accessible to
more looped and compact, genetically secured forms. Furthermore, there are
accessory factors that bias the response of the DNA filament to supercoiling. For
example, small molecules like polyamines, which neutralize the negative charge
repulsions along the phosphate backbone, enhance flexibility and promote writhe
over twist in response to torsion. Such increased flexibility likely pushes the
topological equilibrium from twist toward writhe at tensions thought to exist in
vivo. A predictable corollary is that stiffening DNA antagonizes looping and
bending. Certain sequences are known to be more or less flexible or to exhibit
curvature, and this may affect interactions with binding proteins. In vivo all of
these factors operate simultaneously on DNA that is generally negatively
supercoiled to some degree. Therefore, in order to better understand gene
regulation that involves protein-mediated DNA loops, it is critical to understand
the thermodynamics and kinetics of looping in DNA that is under tension,
negatively supercoiled, and perhaps exposed to molecules that alter elasticity.
Recent experiments quantitatively reveal how much negatively supercoiling DNA
lowers the free energy of looping, possibly biasing the operation of genetic
switches.
PMID- 28510215
TI - Species-specific supercoil dynamics of the bacterial nucleoid.
AB - Bacteria organize DNA into self-adherent conglomerates called nucleoids that are
replicated, transcribed, and partitioned within the cytoplasm during growth and
cell division. Three classes of proteins help condense nucleoids: (1) DNA gyrase
generates diffusible negative supercoils that help compact DNA into a dynamic
interwound and multiply branched structure; (2) RNA polymerase and abundant small
basic nucleoid-associated proteins (NAPs) create constrained supercoils by
binding, bending, and forming cooperative protein-DNA complexes; (3) a multi
protein DNA condensin organizes chromosome structure to assist sister chromosome
segregation after replication. Most bacteria have four topoisomerases that
participate in DNA dynamics during replication and transcription. Gyrase and
topoisomerase I (Topo I) are intimately involved in transcription; Topo III and
Topo IV play critical roles in decatenating and unknotting DNA during and
immediately after replication. RNA polymerase generates positive (+) supercoils
downstream and negative (-) supercoils upstream of highly transcribed operons.
Supercoil levels vary under fast versus slow growth conditions, but what
surprises many investigators is that it also varies significantly between
different bacterial species. The MukFEB condensin is dispensable in the high
supercoil density (sigma) organism Escherichia coli but is essential in
Salmonella spp. which has 15 % fewer supercoils. These observations raise two
questions: (1) How do different species regulate supercoil density? (2) Why do
closely related species evolve different optimal supercoil levels? Control of
supercoil density in E. coli and Salmonella is largely determined by differences
encoded within the gyrase subunits. Supercoil differences may arise to minimalize
toxicity of mobile DNA elements in the genome.
PMID- 28510218
TI - Controlling gene expression by DNA mechanics: emerging insights and challenges.
AB - Transcription initiation is a major control point for the precise regulation of
gene expression. Our knowledge of this process has been mainly derived from
protein-centric studies wherein cis-regulatory DNA sequences play a passive role,
mainly in arranging the protein machinery to coalesce at the transcription start
sites of genes in a spatial and temporal-specific manner. However, this is a
highly dynamic process in which molecular motors such as RNA polymerase II
(RNAPII), helicases, and other transcription factors, alter the level of
mechanical force in DNA, rather than simply a set of static DNA-protein
interactions. The double helix is a fiber that responds to flexural and torsional
stress, which if accumulated, can affect promoter output as well as change DNA
and chromatin structure. The relationship between DNA mechanics and the control
of early transcription initiation events has been under-investigated. Genomic
techniques to display topological stress and conformational variation in DNA
across the mammalian genome provide an exciting new insight on the role of DNA
mechanics in the early stages of the transcription cycle. Without understanding
how torsional and flexural stresses are generated, transmitted, and dissipated,
no model of transcription will be complete and accurate.
PMID- 28510217
TI - Protein-induced DNA linking number change by sequence-specific DNA binding
proteins and its biological effects.
AB - Sequence-specific DNA-binding proteins play essential roles in many fundamental
biological events such as DNA replication, recombination, and transcription. One
common feature of sequence-specific DNA-binding proteins is to introduce
structural changes to their DNA recognition sites including DNA-bending and DNA
linking number change (DeltaLk). In this article, I review recent progress in
studying protein-induced DeltaLk by several sequence-specific DNA-binding
proteins, such as E. coli cAMP receptor protein (CRP) and lactose repressor
(LacI). It was demonstrated recently that protein-induced DeltaLk is an intrinsic
property for sequence-specific DNA-binding proteins and does not correlate to
protein-induced other structural changes, such as DNA bending. For instance,
although CRP bends its DNA recognition site by 90 degrees , it was not able to
introduce a DeltaLk to it. However, LacI was able to simultaneously bend and
introduce a DeltaLk to its DNA binding sites. Intriguingly, LacI also constrained
superhelicity within LacI-lac O1 complexes if (-) supercoiled DNA templates were
provided. I also discuss how protein-induced DeltaLk help sequence-specific DNA
binding proteins regulate their biological functions. For example, it was shown
recently that LacI utilizes the constrained superhelicity (DeltaLk) in LacI-lac
O1 complexes and serves as a topological barrier to constrain free, unconstrained
(-) supercoils within the 401-bp DNA loop. These constrained (-) supercoils
enhance LacI's binding affinity and therefore the repression of the lac promoter.
Other biological functions include how DNA replication initiators lambda O and
DnaA use the induced DeltaLk to open/melt bacterial DNA replication origins.
PMID- 28510219
TI - The dynamic interplay between DNA topoisomerases and DNA topology.
AB - Topological properties of DNA influence its structure and biochemical
interactions. Within the cell, DNA topology is constantly in flux. Transcription
and other essential processes, including DNA replication and repair, not only
alter the topology of the genome but also introduce additional complications
associated with DNA knotting and catenation. These topological perturbations are
counteracted by the action of topoisomerases, a specialized class of highly
conserved and essential enzymes that actively regulate the topological state of
the genome. This dynamic interplay among DNA topology, DNA processing enzymes,
and DNA topoisomerases is a pervasive factor that influences DNA metabolism in
vivo. Building on the extensive structural and biochemical characterization over
the past four decades that has established the fundamental mechanistic basis of
topoisomerase activity, scientists have begun to explore the unique roles played
by DNA topology in modulating and influencing the activity of topoisomerases. In
this review we survey established and emerging DNA topology-dependent protein-DNA
interactions with a focus on in vitro measurements of the dynamic interplay
between DNA topology and topoisomerase activity.
PMID- 28510216
TI - DNA supercoiling is a fundamental regulatory principle in the control of
bacterial gene expression.
AB - Although it has become routine to consider DNA in terms of its role as a carrier
of genetic information, it is also an important contributor to the control of
gene expression. This regulatory principle arises from its structural properties.
DNA is maintained in an underwound state in most bacterial cells and this has
important implications both for DNA storage in the nucleoid and for the
expression of genetic information. Underwinding of the DNA through reduction in
its linking number potentially imparts energy to the duplex that is available to
drive DNA transactions, such as transcription, replication and recombination. The
topological state of DNA also influences its affinity for some DNA binding
proteins, especially in DNA sequences that have a high A + T base content. The
underwinding of DNA by the ATP-dependent topoisomerase DNA gyrase creates a
continuum between metabolic flux, DNA topology and gene expression that underpins
the global response of the genome to changes in the intracellular and external
environments. These connections describe a fundamental and generalised mechanism
affecting global gene expression that underlies the specific control of
transcription operating through conventional transcription factors. This
mechanism also provides a basal level of control for genes acquired by horizontal
DNA transfer, assisting microbial evolution, including the evolution of
pathogenic bacteria.
PMID- 28510221
TI - Development of a dual-expression vector facilitated with selection-free PCR
recombination cloning strategy.
AB - The conventional procedure for the construction of recombinant expression vector
of a target gene includes PCR cloning and restriction enzyme mediated subcloning,
which is time-consuming and sometimes troublesome because of the inefficiency of
ligation. A variety of ligase-independent PCR cloning strategies have been
developed, but they either involve complicated PCR procedures or need other DNA
modifying enzymes. In this study, we report the design, and construction of an
omnipotent expression vector pOmni, with which a target gene can be easily cloned
through innovative selection-free PCR recombination cloning strategy with only
one pair of primer and two times of PCR in one work day, without using any
restriction enzymes, ligase and other DNA modifying enzymes. Furthermore, the
target gene cloned in pOmni is ready to be high-efficiently expressed in either
Escherichia coli cells or eukaryotic cells because of the elaborate design of
compatible T7 promoter and CMV promoter expression elements in the vector. The
cloning capability and reliability of selection-free PCR recombination cloning
with pOmni were validated through cloning of 6 DNA fragments with length from 315
to 4557 bp, and the dual-expression function of the vector was verified through
the cloning and expression of EGFP in E. coli BL21 and HeLa cells. pOmni
developed in our study provides a powerful tool for gene cloning and expression,
and is of special value for researches in which both prokaryotic and eukaryotic
expression of a target gene are necessary.
PMID- 28510222
TI - Primary ectopic breast cancer of the vulva, treated with local excision of the
vulva and sentinel lymph node biopsy: a case report.
AB - Primary breast cancer fairly infrequently occurs in ectopic breast tissue, and
primary ectopic breast cancer of the vulva is particularly rare. Only 26 cases
have been published in the English-language literature, and there has been no
report of primary breast carcinoma of the vulva in Japan. We report a rare case
of primary ectopic breast cancer of the vulva that was treated with local
excision of the vulva and sentinel lymph node biopsy (SLNB). The patient was a 72
year-old woman who had noticed a right vulvar tumor 10 years earlier. The tumor
was excised by the Department of Plastic Surgery of our hospital. The histology
of the vulvar tumor revealed an invasive ductal carcinoma of the breast, and
immunohistochemical staining of the vulvar specimen showed the tumor cells to be
100% estrogen-receptor-positive and 100% progesterone-receptor-positive. All
margins of resection were positive for neoplastic involvement. An additional
local excision of the vulva and right inguinal SLNB were performed in our
department. The intraoperative frozen section was negative for metastasis, and
lymph node dissection was not performed. The final pathology was negative for
residual disease, and a partially normal ductal component was present. Adjuvant
hormonal therapy with an aromatase inhibitor was indicated post-operatively. The
patient was asymptomatic and free of detectable disease at a 6-month follow-up.
Due to the rarity of this diagnosis, there are no established guidelines for
treatment. Although cases in which SLNB was performed are rare, we consider SLNB
to be an effective alternative to inguinal node dissection for ectopic primary
breast cancer of the vulva.
PMID- 28510220
TI - The regulatory role of DNA supercoiling in nucleoprotein complex assembly and
genetic activity.
AB - We argue that dynamic changes in DNA supercoiling in vivo determine both how DNA
is packaged and how it is accessed for transcription and for other manipulations
such as recombination. In both bacteria and eukaryotes, the principal generators
of DNA superhelicity are DNA translocases, supplemented in bacteria by DNA
gyrase. By generating gradients of superhelicity upstream and downstream of their
site of activity, translocases enable the differential binding of proteins which
preferentially interact with respectively more untwisted or more writhed DNA.
Such preferences enable, in principle, the sequential binding of different
classes of protein and so constitute an essential driver of chromatin
organization.
PMID- 28510223
TI - Protein-induced DNA linking number change by sequence-specific DNA binding
proteins and its biological effects.
AB - Sequence-specific DNA-binding proteins play essential roles in many fundamental
biological events such as DNA replication, recombination, and transcription. One
common feature of sequence-specific DNA-binding proteins is to introduce
structural changes to their DNA recognition sites including DNA-bending and DNA
linking number change (DeltaLk). In this article, I review recent progress in
studying protein-induced DeltaLk by several sequence-specific DNA-binding
proteins, such as E. coli cAMP receptor protein (CRP) and lactose repressor
(LacI). It was demonstrated recently that protein-induced DeltaLk is an intrinsic
property for sequence-specific DNA-binding proteins and does not correlate to
protein-induced other structural changes, such as DNA bending. For instance,
although CRP bends its DNA recognition site by 90 degrees , it was not able to
introduce a DeltaLk to it. However, LacI was able to simultaneously bend and
introduce a DeltaLk to its DNA binding sites. Intriguingly, LacI also constrained
superhelicity within LacI-lac O1 complexes if (-) supercoiled DNA templates were
provided. I also discuss how protein-induced DeltaLk help sequence-specific DNA
binding proteins regulate their biological functions. For example, it was shown
recently that LacI utilizes the constrained superhelicity (DeltaLk) in LacI-lac
O1 complexes and serves as a topological barrier to constrain free, unconstrained
(-) supercoils within the 401-bp DNA loop. These constrained (-) supercoils
enhance LacI's binding affinity and therefore the repression of the lac promoter.
Other biological functions include how DNA replication initiators lambda O and
DnaA use the induced DeltaLk to open/melt bacterial DNA replication origins.
PMID- 28510225
TI - Controlling gene expression by DNA mechanics: emerging insights and challenges.
AB - Transcription initiation is a major control point for the precise regulation of
gene expression. Our knowledge of this process has been mainly derived from
protein-centric studies wherein cis-regulatory DNA sequences play a passive role,
mainly in arranging the protein machinery to coalesce at the transcription start
sites of genes in a spatial and temporal-specific manner. However, this is a
highly dynamic process in which molecular motors such as RNA polymerase II
(RNAPII), helicases, and other transcription factors, alter the level of
mechanical force in DNA, rather than simply a set of static DNA-protein
interactions. The double helix is a fiber that responds to flexural and torsional
stress, which if accumulated, can affect promoter output as well as change DNA
and chromatin structure. The relationship between DNA mechanics and the control
of early transcription initiation events has been under-investigated. Genomic
techniques to display topological stress and conformational variation in DNA
across the mammalian genome provide an exciting new insight on the role of DNA
mechanics in the early stages of the transcription cycle. Without understanding
how torsional and flexural stresses are generated, transmitted, and dissipated,
no model of transcription will be complete and accurate.
PMID- 28510224
TI - DNA supercoiling is a fundamental regulatory principle in the control of
bacterial gene expression.
AB - Although it has become routine to consider DNA in terms of its role as a carrier
of genetic information, it is also an important contributor to the control of
gene expression. This regulatory principle arises from its structural properties.
DNA is maintained in an underwound state in most bacterial cells and this has
important implications both for DNA storage in the nucleoid and for the
expression of genetic information. Underwinding of the DNA through reduction in
its linking number potentially imparts energy to the duplex that is available to
drive DNA transactions, such as transcription, replication and recombination. The
topological state of DNA also influences its affinity for some DNA binding
proteins, especially in DNA sequences that have a high A + T base content. The
underwinding of DNA by the ATP-dependent topoisomerase DNA gyrase creates a
continuum between metabolic flux, DNA topology and gene expression that underpins
the global response of the genome to changes in the intracellular and external
environments. These connections describe a fundamental and generalised mechanism
affecting global gene expression that underlies the specific control of
transcription operating through conventional transcription factors. This
mechanism also provides a basal level of control for genes acquired by horizontal
DNA transfer, assisting microbial evolution, including the evolution of
pathogenic bacteria.
PMID- 28510226
TI - The ribosome's energy landscape: Recent insights from computation.
AB - The ever-increasing capacity of computing resources has extended ribosome
calculations from the study of small-scale fluctuations to large-scale barrier
crossing processes. As the field of computational/theoretical biophysics shifts
focus to large-scale conformational transitions, there is a growing need for a
systematic framework to interpret and analyze ribosome dynamics. To this end,
energy landscape principles, largely developed for the study of biomolecular
folding, have proven to be invaluable. These tools not only provide a foundation
for describing simulations but can be used to reconcile experimental results, as
well. In this review, I will discuss recent efforts to employ computational
methods to reveal the characteristics of the ribosome's landscape and how these
studies can help guide a new generation of experiments that more closely probe
the underlying energetics. As a result of these investigations, general
principles about ribosome function are beginning to emerge, including that: (1)
small-scale fluctuations are the result of structure, rather than detailed
energetics, (2) molecular flexibility leads to entropically favored
rearrangements, and (3) tRNA dynamics may be accurately described as diffusive
movement across an energy landscape.
PMID- 28510228
TI - Oriented samples: a tool for determining the membrane topology and the mechanism
of action of cationic antimicrobial peptides by solid-state NMR.
AB - Overuse and misuse of antibiotics have led bacteria to acquire several mechanisms
of resistance. In response to this, researchers have identified natural
antimicrobial peptides as promising candidates to fight against multiresistant
bacteria. However, their mode of action is still unclear, and a better
understanding of the mode of action of these peptides is of primary importance to
develop new peptides displaying high antibacterial activity and low hemolytic
activity. One of the main features that defines the mechanism of action is the
membrane topology of the peptide. Among the spectroscopic techniques, solid-state
NMR is the technique of choice for determining the location of the peptide within
the membrane. It can be achieved by performing experiments with oriented samples.
In the literature, the two most common types of oriented samples are bicelles and
phospholipids mechanically oriented between glass plates. The mode of
perturbation of the membrane-active peptide can be studied by phosphorus-31 and
deuterium NMR. On the other hand, several experiments such as nitrogen-15 and
fluorine solid-state NMR, that require labeled peptides, can give valuable
information on the membrane topology of the peptide. The combination of the
latter techniques allows the determination of a precise topology, thus a better
knowledge of the molecular determinants involved in the membrane interactions of
antimicrobial peptides.
PMID- 28510230
TI - How to test bioinformatics software?
AB - Bioinformatics is the application of computational, mathematical and statistical
techniques to solve problems in biology and medicine. Bioinformatics programs
developed for computational simulation and large-scale data analysis are widely
used in almost all areas of biophysics. The appropriate choice of algorithms and
correct implementation of these algorithms are critical for obtaining reliable
computational results. Nonetheless, it is often very difficult to systematically
test these programs as it is often hard to verify the correctness of the output,
and to effectively generate failure-revealing test cases. Software testing is an
important process of verification and validation of scientific software, but very
few studies have directly dealt with the issues of bioinformatics software
testing. In this work, we review important concepts and state-of-the-art methods
in the field of software testing. We also discuss recent reports on adapting and
implementing software testing methodologies in the bioinformatics field, with
specific examples drawn from systems biology and genomic medicine.
PMID- 28510231
TI - Quantum effects in dynamics of water and other liquids of light molecules.
AB - Nuclear quantum effects in atomic motions are well known at low temperatures
[Formula: see text] K, but analyses of structural relaxation in liquids and
description of the glass transition traditionally neglect quantum effects at
higher temperatures, [Formula: see text] K. Recent studies, however, suggested
that nuclear quantum effects in systems of light molecules (e.g., water) might
play an important role in structural dynamics and provide non-negligible
contributions at such temperatures, and even up to ambient temperature. In this
article, we discuss experimental evidences of the quantum effects in glass
transition in liquids of light molecules and possible theoretical descriptions of
these effects. We show that quantum effects may qualitatively change the
temperature behavior of the structural relaxation time in supercooled liquids
leading to deviations of some well-established properties of the glass transition
when it happens at low temperatures. We also demonstrate that unusual behavior of
water dynamics at low temperatures, including apparent fragile-to-strong
crossover, can be ascribed to nuclear quantum effects.
PMID- 28510227
TI - Kinesin Motor Enzymology: Chemistry, Structure, and Physics of Nanoscale
Molecular Machines.
AB - Molecular motors are enzymes that convert chemical potential energy into
controlled kinetic energy for mechanical work inside cells. Understanding the
biophysics of these motors is essential for appreciating life as well as
apprehending diseases that arise from motor malfunction. This review focuses on
kinesin motor enzymology with special emphasis on the literature that reports the
chemistry, structure and physics of several different kinesin superfamily
members.
PMID- 28510234
TI - Deriving biomedical diagnostics from NMR spectroscopic data.
AB - Biomedical spectroscopic experiments generate large volumes of data. For
accurate, robust diagnostic tools the data must be analyzed for only a few
characteristic observations per subject, and a large number of subjects must be
studied. We describe here two of the current data analytic approaches applied to
this problem: SIMCA (principal component analysis, partial least squares), and
the statistical classification strategy (SCS). We demonstrate the application of
the SCS by three examples of its use in analyzing 1H NMR spectra: screening for
colon cancer, characterization of thyroid cancer, and distinguishing cancer from
cholangitis in the biliary tract.
PMID- 28510229
TI - A change of heart: oxidative stress in governing muscle function?
AB - Redox/cysteine modification of proteins that regulate calcium cycling can affect
contraction in striated muscles. Understanding the nature of these modifications
would present the possibility of enhancing cardiac function through reversible
cysteine modification of proteins, with potential therapeutic value in heart
failure with diastolic dysfunction. Both heart failure and muscular dystrophy are
characterized by abnormal redox balance and nitrosative stress. Recent evidence
supports the synergistic role of oxidative stress and inflammation in the
progression of heart failure with preserved ejection fraction, in concert with
endothelial dysfunction and impaired nitric oxide-cyclic guanosine monophosphate
protein kinase G signalling via modification of the giant protein titin. Although
antioxidant therapeutics in heart failure with diastolic dysfunction have no
marked beneficial effects on the outcome of patients, it, however, remains
critical to the understanding of the complex interactions of
oxidative/nitrosative stress with pro-inflammatory mechanisms, metabolic
dysfunction, and the redox modification of proteins characteristic of heart
failure. These may highlight novel approaches to therapeutic strategies for heart
failure with diastolic dysfunction. In this review, we provide an overview of
oxidative stress and its effects on pathophysiological pathways. We describe the
molecular mechanisms driving oxidative modification of proteins and subsequent
effects on contractile function, and, finally, we discuss potential therapeutic
opportunities for heart failure with diastolic dysfunction.
PMID- 28510232
TI - Network modelling of gene regulation.
AB - Gene regulatory network (GRN) modelling has gained increasing attention in the
past decade. Many computational modelling techniques have been proposed to
facilitate the inference and analysis of GRN. However, there is often confusion
about the aim of GRN modelling, and how a gene network model can be fully
utilised as a tool for systems biology. The aim of the present article is to
provide an overview of this rapidly expanding subject. In particular, we review
some fundamental concepts of systems biology and discuss the role of network
modelling in understanding complex biological systems. Several commonly used
network modelling paradigms are surveyed with emphasis on their practical use in
systems biology research.
PMID- 28510233
TI - Filamin structure, function and mechanics: are altered filamin-mediated force
responses associated with human disease?
AB - The cytoskeleton framework is essential not only for cell structure and stability
but also for dynamic processes such as cell migration, division and
differentiation. The F-actin cytoskeleton is mechanically stabilised and
regulated by various actin-binding proteins, one family of which are the filamins
that cross-link F-actin into networks that greatly alter the elastic properties
of the cytoskeleton. Filamins also interact with cell membrane-associated
extracellular matrix receptors and intracellular signalling proteins providing a
potential mechanism for cells to sense their external environment by linking
these signalling systems. The stiffness of the external matrix to which cells are
attached is an important environmental variable for cellular behaviour. In order
for a cell to probe matrix stiffness, a mechanosensing mechanism functioning via
alteration of protein structure and/or binding events in response to external
tension is required. Current structural, mechanical, biochemical and human
disease-associated evidence suggests filamins are good candidates for a role in
mechanosensing.
PMID- 28510236
TI - ?
PMID- 28510237
TI - [Time for legislation on the "doctor consultation apps"].
PMID- 28510238
TI - ?
PMID- 28510235
TI - Surfactants in Acute Respiratory Distress Syndrome in Infants and Children: Past,
Present and Future.
AB - There is a lack of definitive data on the effective management of acute
respiratory distress syndrome (ARDS) in infants and children. The development and
validation of the Berlin definition (BD) for ARDS and the Pediatric Acute Lung
Injury Consensus Conference (PALICC) recommendations in children represented a
major advance in optimizing research and treatment, mainly due to the
introduction of a severe ARDS category. Proposed reasons for the lack of
consistent results with surfactants in children and infants compared with
neonates include different causes, type of lung damage (direct or indirect),
timing and mode of administration as well as the type of surfactant used.
Secretory phospholipase A2 plays an important role in inflammation and possible
dysfunction of surfactants in ARDS. Bronchoalveolar lavage (BAL) with normal
saline and surfactant allows the removal of inhaled material, the recruitment of
non-ventilating areas and the maintenance of the surfactant pool size. BAL with
diluted surfactant allows rapid absorption of the surfactant at the air/liquid
interface, which blocks the progression of pathological lung disease and in turn
disrupts the inflammatory cycle. Importantly, it is now recognized that the type
of surfactant, the time of administration and the method of administration could
all play an important role in the management of ARDS, and there is evidence that
surfactant is effective and well tolerated in children and infants with ARDS.
PMID- 28510239
TI - ?
PMID- 28510240
TI - [Warfarin should not be recommended to anyone with atrial fibrillation].
PMID- 28510241
TI - [Ketosis-prone type 2 diabetes can be expected to increase in Sweden].
PMID- 28510242
TI - ?
AB - Endoscopic surveillance after colorectal polypectomy These guidelines for
endoscopic surveillance after colorectal polypectomy are based on the
recommendations published by European Society of Gastrointestinal Endoscopy
(ESGE) in 2013. A precondition for the guidelines is that patients have undergone
a high-quality colonoscopy, including complete removal and histopathological
evaluation of all detected neoplastic lesions. Current research has made it
possible to stratify patients into a low-risk and a high-risk group in terms of
metachronous cancer. Low-risk group patients (1-2 tubular adenomas <10 mm in
size) are recommended a surveillance colonoscopy 10 years after the index
colonoscopy if the patient is less than 50 years old, otherwise not. High-risk
group patients (adenomas with villous histology or high grade dysplasia or >=10
mm in size, or >= 3 adenomas), should undergo a repetition colonoscopy 3 years
after the index colonoscopy. If high-risk adenomas are detected at first or
subsequent surveillance colonoscopy, a 3-year repetition of the next endoscopic
examination is recommended. If a high-risk patient has no high-risk adenomas at
the first surveillance colonoscopy, a 5-year period is recommended until the
second surveillance colonoscopy. ESGE recommends termination of the follow-up at
80 years of age although individualised recommendations should consider general
health and co-morbidity of the patients as well as findings at previous
colonoscopies.
PMID- 28510243
TI - ?
AB - High quality colonoscopy must be secured Colonoscopy plays a key role in the work
up of digestive diseases and constitutes the cornerstone in colorectal cancer
diagnosis and prevention. Data suggest that the quality of colonoscopy varies
widely between different endoscopists. This article summarizes current evidence
and expert consensus on quality indicators, along with the evidence supporting
their use in benchmarking, quality reporting, and continuous quality improvement
in order to secure high quality colonoscopy. In particular, four quality
indicators, i.e. adenoma detection rate, compliance with guidelines on intervals
for endoscopic surveillance, cecal intubation rate and complications, should be
monitored in endoscopy units to ensure that colonoscopy practice is of high
quality. Proper performance and documentation of high quality colonoscopy is
critical for reducing colorectal cancer incidence and mortality.
PMID- 28510244
TI - ?
PMID- 28510245
TI - Association of three common single nucleotide polymorphisms of SLC7A7 with the
development of glioma in a Chinese population.
AB - Gliomas are brain tumors that can be seriously damaging to human health. The SLC7
family is involved in amino acid or peptide transportation. The relationship
between SLC7A7 polymorphisms and the development of glioma has been reported
previously by a few studies. Therefore, we performed a hospital based case
control study to investigate the association of three common SNPs (rs12888930,
rs12436190, and rs2065134) of SLC7A7 with the development of glioma in a Chinese
population. From January 2014 to December 2015, 122 patients with glioma and 252
individuals (controls) were recruited from the department of neurosurgery of
Tangshan People's Hospital affiliated to North China University of Science and
Technology. SLC7A7 rs12888930, rs12436190, and rs2065134 genotyping was performed
by the polymerase chain reaction-restriction fragment length polymorphism method.
Multiple logistic regression analysis showed that a significantly higher risk of
glioma was harbored by the GG and AG + GG genotypes than by the AA genotype; OR
(95%CI) was 2.24 (1.18-4.22) and 1.59 (1.01-2.60), respectively. However, no
significant relationship was observed between SLC7A7 rs12888930 and rs2065134 and
the risk of glioma. In conclusion, this study reports a significant association
between SLC7A7 rs12436190 and the risk of glioma in a Chinese population.
PMID- 28510246
TI - Molecular cloning and differential expression of the glucocorticoid receptorgene
in the estuarine tapertail anchovy Coilia nasus.
AB - To understand the regulation of the glucocorticoid receptor gene (Gcr) during
loading and transport stress in fish, the Gcr gene of Coilia nasus was cloned.
Gcr in C. nasus is expressed strongly in the liver and muscle, and less
stronglyin the gills, brain, spleen, intestine, trunk kidney, and head kidney.
Gcr expression in both the liver and muscle was increased by loading and
transport stress. NaCl reduced the death rate caused by loading and transport
stress, and the expression of Gcr in liver and muscle differed significantly
between the NaCl and non-NaCl groups. To investigate whether the elevated Gcr
transcripts were translated into protein, proteins extracted from the liver and
muscle were analyzed. In both tissues, C. nasus GCR protein expression patterns
paralleled those of Gcr mRNA during stress.
PMID- 28510247
TI - Characterization and development of 56 EST-SSR markers derived from the
transcriptome of Odontobutis potamophila.
AB - Expressed sequence tags (ETSs) are the sources of microsatellite development. In
this study, we isolated and characterized microsatellite markers for Odontobutis
potamophila by using Illumina RNA-sequencing. We sequenced a large number of ESTs
and screened 200 potential microsatellites. Consequently, a total of 56 novel
polymorphic microsatellite repeat markers were identified in thirty-two
individuals from a wild population area (Jiande, Zhejiang Province, China). The
number of alleles per locus varied from two to eight, the observed heterozygosity
(HO) ranged from 0.03571 to 0.9375, and the expected heterozygosity (HE) ranged
from 0.14326 to 0.81549. The average number of alleles, HO, and HE were 5.0,
0.4467, and 0.5518, respectively. By the calculation, the range of polymorphism
information content (PIC) was 0.1177-0.8492. Most of the loci showed moderate or
high polymorphism. These newly developed EST-simple sequence repeat (EST-SSR)
markers would serve as an efficient tool for analyzing population connectivity
and provide sufficient information for genetic diversity research, parentage, and
molecular breeding of O. potamophila and other fishes with similar genetic
relationship.
PMID- 28510248
TI - CADM1 mRNA expression and clinicopathological significance in esophageal squamous
cell carcinoma tissue.
AB - The mRNA expression of cell adhesion molecule 1 (CADM1) and its
clinicopathological significance in esophageal squamous cell carcinoma (ESCC)
tissues were investigated. CADM1 mRNA and protein expression were detected in
tissue samples from 50 patients with ESCC by reverse transcription-polymerase
chain reaction (RT-PCR) and streptavidin-peroxidase (SP) immunohistochemistry;
adjacent tissues served as controls. The average CADM1 mRNA expression was
significantly downregulated in the cancer tissues (0.522 +/- 0.247) than in the
controls (0.871 +/- 0.192), (t = 7.882, P < 0.05). CADM1 mRNA expression was
significantly downregulated in ESCC patients with positive lymph node metastasis
than in those with negative lymph node metastasis (t = 3.207, P < 0.05). There
was a correlation between CADM1 mRNA expression and tumor-node-metastasis (TNM)
stage (t = 2.673, P < 0.050), but not with age, gender, and histological grade (P
> 0.05). The positive expression rate of CADM1 protein in the 50 cases of ESCC
was significantly lower than that of the control group (chi2 = 29.87, P < 0.01).
Out of 28 patients with non-lymph node metastasis, 20 (71.43%) positively
expressed CADM1; out of 22 patients with lymph node metastasis, only 7 (31.82%)
positively expressed CADM1. There was a significant difference in the positive
protein expression rates of CADM1 between the two groups (chi2 = 7.782, P <
0.01). CADM1 mRNA expression was highly upregulated in normal tissues compared to
ESCC tissues, indicating that the loss of CADM1 expression influenced the
pathogenesis, invasion, and metastasis of ESCC, and allowing for the prognosis of
the disease in patients with ESCC after treatment.
PMID- 28510249
TI - Mechanism of pingyangmycin-induced apoptosis of cultured human umbilical vein
endothelial cells.
AB - In this study, we investigated the effects of pingyangmycin (PYM) on the growth
inhibition and apoptosis of human umbilical vein endothelial cells (HUVEC). In
this study, we aimed to explore the optimal concentration of PYM to induce the
apoptosis of HUVEC and to determine its mechanism of action. After treatment of
HUVEC with different concentrations of PYM for 24 h, cell counting kit-8 (CCK-8)
was used to detect growth inhibiting effects. Annexin V-FITC/propidium iodide
stain was used to detect apoptosis, and western blot was used to detect the
expression of glucose-related protein 78 (GPR78) and C/EBP homologous protein
(CHOP) endoplasmic reticulum stress proteins. With increasing PYM concentration,
the growth inhibition of HUVEC increased (P < 0.05), the apoptotic numbers of
HUVEC increased (P < 0.05), with higher PYM concentrations inducing necrosis, and
the protein expression of GRP78 and CHOP increased (P < 0.05). PYM could
obviously inhibit the proliferation and promote the apoptosis of HUVEC. Necrotic
cells were more prevalent than apoptotic cells at high PYM concentrations. This
study helped to determine the proper concentration of PYM to induce more
apoptosis than necrosis, which is critical to minimize inflammation, enhance the
healing of the skin, and maintain safety for the patient. PYM might induce HUVEC
apoptosis through the endoplasmic reticulum stress pathway.
PMID- 28510250
TI - A set of novel microsatellite markers developed for an economically important
tree, Dracontomelon duperreanum, in China.
AB - Dracontomelon duperreanum, the most representative species of the family
Anacardiaceae, is an important multipurpose tree in China and Vietnam. However,
no genetic diversity studies have been reported on this species. In this study,
we identified 11 microsatellite markers for D. duperreanum by using the
restriction-site-associated DNA sequencing (RAD-seq) method and examined their
polymorphisms in 22 samples obtained from the South China Botanical Garden, South
China. We could detect only two or three alleles for each microsatellite marker.
The mean observed and expected heterozygosities were 0.41 and 0.39, respectively,
which were lower than those reported for the species with similar life history
forms. These relatively low genetic diversities in this common plant species are
unexpected and might have resulted from its extensive cultivation. To our
knowledge, this is the first report of microsatellite markers in the genus
Dracontomelon. These microsatellite markers will be valuable for studying the
genetic diversities and structures in D. duperreanum and other Dracontomelon
species.
PMID- 28510252
TI - Assessing non-additive effects in GBLUP model.
AB - Understanding non-additive effects in the expression of quantitative traits is
very important in genotype selection, especially in species where the commercial
products are clones or hybrids. The use of molecular markers has allowed the
study of non-additive genetic effects on a genomic level, in addition to a better
understanding of its importance in quantitative traits. Thus, the purpose of this
study was to evaluate the behavior of the GBLUP model in different genetic models
and relationship matrices and their influence on the estimates of genetic
parameters. We used real data of the circumference at breast height in Eucalyptus
spp and simulated data from a population of F2. Three commonly reported kinship
structures in the literature were adopted. The simulation results showed that the
inclusion of epistatic kinship improved prediction estimates of genomic breeding
values. However, the non-additive effects were not accurately recovered. The
Fisher information matrix for real dataset showed high collinearity in estimates
of additive, dominant, and epistatic variance, causing no gain in the prediction
of the unobserved data and convergence problems. Estimates presented differences
of genetic parameters and correlations considering the different kinship
structures. Our results show that the inclusion of non-additive effects can
improve the predictive ability or even the prediction of additive effects.
However, the high distortions observed in the variance estimates when the Hardy
Weinberg equilibrium assumption is violated due to the presence of selection or
inbreeding can converge at zero gains in models that consider epistasis in
genomic kinship.
PMID- 28510251
TI - Short-term effects of green tea chronotherapy on the metabolic homeostasis of
mice on different diets.
AB - Biological rhythms can be defined as changes in physiological or behavioral
variables that repeat at certain time intervals. Rhythms that last approximately
24 h are referred to as circadian rhythms. Modern lifestyles have drastically
affected human habits, as well as the population's eating habits. These changes
have generated an epidemic of metabolic syndromes, such as obesity and diabetes.
In an attempt to combat obesity, populations have attempted to use many different
herbal remedies and plant-based drugs, the most common of which is Camellia
sinensis, or green tea. Most of the studies on the effects of C. sinensis on
maintaining body weight have reported the involvement of this substance in lipid
oxidation. The objective of this study was to evaluate how the administration of
C. sinensis at different times of day influenced changes in body weight, blood
glucose levels, and food intake of mice kept under different diet conditions. The
structural organization of abdominal adipose tissue was also evaluated, as were
certain aspects of lipid metabolism and overall synthetic activity in the liver,
adipose tissue, and ovaries. The results obtained suggest that the intake of
green tea in the light phase of the day stimulates weight loss, regardless of the
diet ingested. Neither glucose levels nor the structural organization of adipose
tissue was found to be altered in any of the experimental groups. Neither diet
nor the time at which the green tea was administered was found to have any
effects on the amount of food the mice consumed. The time at which green tea was
consumed and the type of diet both influenced LXRalphabeta nuclear receptor
expression, as well as the expression of fibrillarin in the liver and ovaries,
although this influence was tissue specific.
PMID- 28510253
TI - Feline immunodeficiency virus and feline leukemia virus: frequency and associated
factors in cats in northeastern Brazil.
AB - Our aims were to determine the frequencies of feline immunodeficiency virus (FIV)
and feline leukemia virus (FeLV) in owned and stray cats in the northeastern
region of Brazil, ascertain the status of FeLV infection, and investigate
potential associated factors among the owned cats. Blood samples from 200
asymptomatic owned cats and 30 stray cats were processed using nested PCR and
commercial immunochromatographic tests to diagnose infections. To evaluate the
factors associated with FIV and/or FeLV in owned cats, a semi-structured
interview was conducted with each owner about the animal's environment, and these
data were subjected to unconditional logistic regression. The frequencies for
owned cats were 6% (12/200) and 3% (6/200) for FIV and FeLV, respectively. No
owned cat was positive for both viruses. Stray cats showed frequencies of 6.66%
(2/30) and 0% (0/30) for FIV and FeLV, respectively. Contact with other cats and
living in peri-urban areas were considered to be risk factors (P < 0.05) for FIV.
We did not identify any factors associated with infections with FeLV. Our results
confirm the presence of these two retroviruses in the region under study. Our use
of different diagnostic techniques allowed us to determine the frequency of
retroviruses in the feline population more accurately, particularly with regard
to infections by FeLV, which have complex pathogenesis.
PMID- 28510254
TI - Effects of mutant TDP-43 on the Nrf2/ARE pathway and protein expression of MafK
and JDP2 in NSC-34 cells.
AB - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects
motor neurons and lacks an effective treatment. The disease pathogenesis has not
been clarified at present. Pathological transactive response DNA-binding protein
43 (TDP-43) plays an important role in the pathogenesis of ALS. Nuclear
translocation of nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) is
found in a mutant TDP-43 transgenic cell model, but its downstream antioxidant
enzyme expression is decreased. To elucidate the specific mechanism of Nrf2/ARE
(antioxidant responsive element) signaling dysfunction, we constructed an ALS
cell model with human mutant TDP-43 using the NSC-34 cell line to evaluate the
impact of the TDP-43 mutation on the Nrf2/ARE pathway. We found the nuclear
translocation of Nrf2, but the expression of total Nrf2, cytoplasmic Nrf2, and
downstream phase II detoxifying enzyme (NQO1) was decreased in NSC-34 cells
transfected with the TDP-43-M337V plasmid. Besides, TDP-43-M337V plasmid
transfected NSC-34 cells were rounded with reduced neurites, shortened axons,
increased levels of intracellular lipid peroxidation products, and decreased
viability, which suggests that the TDP-43-M337V plasmid weakened the antioxidant
capacity of NSC-34 cells and increased their susceptibility to oxidative damage.
We further showed that expression of the MafK protein and the Jun dimerization
protein 2 (JDP2) was reduced in TDP-43-M337V plasmid-transfected NSC-34 cells,
which might cause accumulation of Nrf2 in nuclei but a decrease in NQO1
expression. Taken together, our results confirmed that TDP-43-M337V impaired the
Nrf2/ARE pathway by reducing the expression of MafK and JDP2 proteins, and
provided information for further research on the molecular mechanisms of TDP-43
M337V in ALS.
PMID- 28510255
TI - Adaptability and stability of soybean cultivars for grain yield and seed quality.
AB - This study aimed at verifying the adaptability and stability of soybean
cultivars, considering the grain yield and quality of seeds, adopting univariate
and multivariate approaches. The experiments were conducted in two crops, three
environments, in 2013/2014 and 2014/2015 crop seasons, in the county of
Inconfidentes, Lavras, and Patos de Minas, in the Minas Gerais State, Brazil. We
evaluated 17 commercial soybean cultivars. For adaptability and stability
evaluations, the Graphic and GGE biplot methods were employed. Previously, a
selection index was estimated based on the sum of the standardized variables (Z
index). The data relative to grain yield, mass of one thousand grain, uniformity
test (sieve retention), and germination test were standardized (Zij) per
cultivar. With the sum of Zij, we obtained the selection index for the four
traits evaluated together. In the Graphic method evaluation, cultivars NA 7200 RR
and CD 2737 RR presented the highest values for selection index Z. By the GGE
biplot method, we verified that cultivar NA 7200 RR presented greater stability
in both univariate evaluations, for grain yield, and for selection index Z.
PMID- 28510256
TI - Interregional cytogenetic comparisons in Halichoeres and Thalassoma wrasses
(Labridae) of coastal and insular regions of the southwestern Atlantic.
AB - The distribution patterns of marine biodiversity are complex, resulting from
vicariant events and species dispersion, as well as local ecological and adaptive
conditions. Furthermore, the wide geographic distribution of some species may be
hindered by biogeographical barriers that can interfere in the gene flow.
Cytogenetic analyses in marine fishes, especially those involving populations in
small remote insular environments, remain scarce. In the Western Atlantic,
species of wrasses from the genera Halichoeres and Thalassoma occur in
biogeographic arrangements that make it possible to analyze cytogenetic patterns
between coastal and widely separated island populations. Species of these genera
were punctually analyzed in some Atlantic regions. In this study, we compared
several chromosomal features, such as karyotype macrostructure, heterochromatic
patterns, patterns of base-specific fluorochromes, Ag-NORs, and 18S and 5S
ribosomal sites in Thalassoma noronhanum, Halichoeres poeyi, and Halichoeres
radiatus individuals from distinct coastal or insular regions of Atlantic.
Notably, all of them are characterized by multiple 18S and 5S rDNA sites with
syntenic arrangements in some chromosome pairs. Individuals of T. noronhanum
(between the insular regions of Rocas Atoll and Fernando de Noronha Archipelago -
FNA) and H. poeyi (coastal areas from Northeastern Brazil) show no detectable
differences among their cytogenetic patterns. On the other hand, H. radiatus from
FNA and Sao Pedro and Sao Paulo Archipelago exhibit differences in the frequency
of rDNA sites that could suggest some level of population structuring between
these insular regions. Interregional cytogenetic inventories of marine species
with wide geographic distribution need to be rapidly expanded. These data will
allow a better understanding of the level of chromosomal stability between vast
oceanic spaces, which may be less than previously thought.
PMID- 28510257
TI - Strategy for selection of soybean genotypes tolerant to drought during
germination.
AB - Water deficit is the main reason for instability in the context of soybean
culture. The development of strategies for the selection of more tolerant
genotypes is necessary. These strategies include the use of polyethylene glycol
6000 solutions (PEG-6000) for conducting the germination test under conditions of
water restriction. Thus, the objective of this study was to determine the osmotic
potential and the main characteristics that promote the discrimination of soybean
genotypes with regard to water stress tolerance during germination and the vigor
test. Thirteen soybean cultivars were used. The seeds were allowed to germinate
on sheets of germitest paper moistened in solution with PEG-6000, simulating
different levels of water availability, which is expressed as osmotic potential
(0.0, -0.2, -0.4, and -0.6 MPa). We assessed germination, length, and dry mass
for seedlings and seeds, as well as reserve dynamics. Germination and variables
related to the dynamics of reservation have great influence on the expression of
variability in environments under stress. Among the different osmotic potentials,
the -0.2 MPa was the most efficient for the expression of genetic variability
among the cultivars. Conducting the germination test with PEG-6000 solution to
0.2 MPa was efficient for selecting soybean cultivars tolerant to water stress.
This was accomplished by evaluating the percentage of germination, along with
variables related to the dynamics of reservation.
PMID- 28510258
TI - Diversity of plant growth-promoting bacteria associated with sugarcane.
AB - The sugarcane (Saccharum spp) presents economic importance, mainly for tropical
regions, being an important Brazilian commodity. However, this crop is strongly
dependent on fertilizers, mainly nitrogen (N). This study assessed the plant
growth-promoting bacteria (PGPB) associated with sugarcane that could be used as
a potential inoculant to the crop. We evaluated the genetic diversity of PGPB in
the plant tissue of sugarcane varieties (RB 867515, RB 1011, and RB 92579). The
primer BOX-A1R was used to differentiate the similar isolated and further
sequencing 16S rRNA ribosomal gene. The 16S rRNA gene showed the presence of
seven different genera distributed into four groups, the genus Bacillus, followed
by Paenibacillus (20%), Burkholderia (14%), Herbaspirillum (6%), Pseudomonas
(6%), Methylobacterium (6%), and Brevibacillus (3%). The molecular
characterization of endophytic isolates from sugarcane revealed a diversity of
bacteria colonizing this plant, with a possible biotechnological potential to be
used as inoculant and biofertilizers.
PMID- 28510259
TI - 27th Meeting of the European Association for the Study of Diabetes Eye
Complications Study Group (EASDec).
AB - Abstracts will be available online on 25 May 2017.
PMID- 28510260
TI - Markers of enteral adaptation in pediatric short bowel syndrome.
AB - BACKGROUND: The aim of this study was to ascertain if prospective determination
of specific gut hormones and growth factors could predict bowel adaptation in
children with short bowel syndrome (SBS). METHODS: We studied independence from
parenteral nutrition (PN) as the short-term result and discontinuation of enteral
nutrition (EN) as the long-term result from a retrospective chart review of seven
patients with SBS, who were managed in the absence of growth retardation. The
correlation between increased number of enteral feeds or enteral nutrients and
fasting serum gastrin, glucagon-like peptide 2 (GLP-2), citrulline, and D-amino
acid oxidase (DAO) activity was analyzed. Five patients were weaned from PN, and
two from EN. RESULTS: Fasting serum gastrin was significantly higher and serum
GLP-2 lower in the PN-dependent patients than in the patients weaned from EN. The
upper limit of fasting serum gastrin for PN independence and for EN independence
was 300 and 200 pg/mL, respectively. The lower limit of fasting serum citrulline
for PN independence was 15 MUmol/L. The relationship between serum citrulline and
DAO and the course of bowel adaptation, however, was poor. CONCLUSIONS: Serum
citrulline is a predictor of PN independence in children with SBS. Fasting serum
gastrin and GLP-2 are indicators for adaptation of the residual intestine, but
this was a small study and further larger prospective trials are required to
confirm these results.
PMID- 28510261
TI - Constraints on trait combinations explain climatic drivers of biodiversity: the
importance of trait covariance in community assembly.
AB - Trade-offs maintain diversity and structure communities along environmental
gradients. Theory indicates that if covariance among functional traits sets a
limit on the number of viable trait combinations in a given environment, then
communities with strong multidimensional trait constraints should exhibit low
species diversity. We tested this prediction in winter annual plant assemblages
along an aridity gradient using multilevel structural equation modelling.
Univariate and multivariate functional diversity measures were poorly explained
by aridity, and were surprisingly poor predictors of community richness. By
contrast, the covariance between maximum height and seed mass strengthened along
the aridity gradient, and was strongly associated with richness declines.
Community richness had a positive effect on local neighbourhood richness,
indicating that climate effects on trait covariance indirectly influence
diversity at local scales. We present clear empirical evidence that declines in
species richness along gradients of environmental stress can be due to increasing
constraints on multidimensional phenotypes.
PMID- 28510262
TI - What is your diagnosis? Pancreatic aspirate from a cat.
PMID- 28510263
TI - Reply.
PMID- 28510266
TI - Look At That! Video Chat and Joint Visual Attention Development Among Babies and
Toddlers.
AB - Although many relatives use video chat to keep in touch with toddlers, key
features of adult-toddler interaction like joint visual attention (JVA) may be
compromised in this context. In this study, 25 families with a child between 6
and 24 months were observed using video chat at home with geographically
separated grandparents. We define two types of screen-mediated JVA (across- and
within-screen) and report age-related increases in the babies' across-screen JVA
initiations, and that family JVA usage was positively related to babies' overall
attention during video calls. Babies today are immersed in a digital world where
formative relationships are often mediated by a screen. Implications for both
infant social development and developmental research are discussed.
PMID- 28510265
TI - Severity and outcome of the norovirus infection in children after intestinal
transplantation.
AB - In immunocompromised patients, the NoV infection is prolonged and severe. We
retrospectively studied the severity of the NoV infection in children after an
ITx, the treatment, and the long-term evolution. Norovirus PCR in stools was
positive for 19 children in 21 separate episodes. The infection was symptomatic
in 18 cases. At diagnosis, the median weight loss was 5% (0-11) and the
creatinine clearance was 75 mL/min/1.73 m2 (19-142). On 14 digestive biopsies,
the pathological findings were non-specific with a constant mononuclear
infiltration, showing signs of rejection in one case. Fifteen children in 17
cases were hospitalized for a median duration of 41 days (0-119) with IV
infusions for 33 days (0-120). The viral shedding lasted 78 days (20-360). Nine
children with severe or prolonged diarrhea received intravenous IGs and four of
them additional NTZ. On follow-up, five other children developed a rejection 12
months (1-33) after NoV infection. Four uncontrolled rejections led to graft
removal. Children mostly needed hospital admission and IV rehydration, but the
symptoms upon presentation were moderate. Symptoms and shedding durations are
prolonged as expected. The treatment efficacy cannot be assessed. The rejection
induction by the NoV cannot be excluded.
PMID- 28510267
TI - The Jack Wills crowd: towards a sociology of an elite subculture.
AB - British sociologists have long been interested in youth sub-cultures. However
British sociologists have tended to focus on working class subcultures and
avoided engagement with exclusive sub-cultures of elite social groups. This
article seeks to attend to this gap by examining the subculture of a British
elite: ex-public school students at select universities in the UK in the twenty
first century. This group consists of a relatively small group of young adults,
aged between 18 and 23, who attended public schools, especially one of the nine
Clarendon schools (Eton, Winchester, Westminster, St. Paul's, Merchant Taylor's,
Shrewsbury, Rugby, Harrow and Charterhouse), and were students at a selective
group of British universities, primarily Oxford and Cambridge, Durham, Bristol,
Exeter, Bath, Manchester, St Andrews and Edinburgh. The article examines the way
in which this group has reconfigured and re-constituted itself in the face of
globalizing challenges. Specifically, it examines the way in which participation
of ex-public school students in events run by and under the patronage of the high
street retailing company, Jack Wills, has played a galvanising role for this
group in the last decade. The Jack Wills crowd is an example of how some young
adults form exclusive social networks and reproduce prevailing forms of
privilege. The social networks built around the Jack Wills subculture is likely
to provide them with advantages in the job market through a prodigious network of
connections and patrons. The Jack Wills subculture potentially contributions to
the socio-economic reproduction of the higher professional middle classes.
PMID- 28510268
TI - Effect of intervention initiation timing of pulsed electromagnetic field on
ovariectomy-induced osteoporosis in rats.
AB - The aim of this study is to explore the effect of timing of initiation of pulsed
electromagnetic field (PEMF) therapy on bone mass, microarchitecture, and
biomechanical properties, and to investigate receptor activator of NF-kB (RANK)
expression in ovariectomized (OVX) rats. Sixty female Sprague-Dawley rats were
randomly divided into two equal batches of three groups each (10 rats in each
group). The first batch comprised of sham-operated (Sham-0 group), ovariectomized
(OVX-0 group), and ovariectomized plus treated with PEMF starting from the day of
OVX (Early PEMF group). The second batch comprised of sham-operated (Sham-12
group), ovariectomized (OVX-12 group), and ovariectomized plus treated with PEMF
starting 12 weeks after OVX (Late PEMF group). Rats (whole body) in the early and
late PEMF groups were exposed to PEMF (3.8 mT peak, 8 Hz pulse burst repetition
rate). After 12 weeks of PEMF therapy, Early PEMF prevented OVX-induced
deterioration in bone mineral density (BMD) and mechanical properties in lumbar
vertebral body and femur, and deterioration in bone microarchitecture in lumbar
vertebral body and proximal tibia. Late PEMF intervention only inhibited
deterioration of BMD, bone microarchitecture, and mechanical properties in lumbar
vertebral body. Both early and late PEMF therapy suppressed RANK protein
expression in OVX rats without a concomitant effect on RANK mRNA expression.
These results demonstrate that timing of initiation of PEMF therapy plays an
important role in achieving optimal beneficial effects. The specific PEMF
parameters may exert these favorable biological responses, at least partially,
via inhibition of protein expression of RANK. Bioelectromagnetics. 38:456-465,
2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28510270
TI - Mouse Fgf8-Cre-LacZ lineage analysis defines the territory of the postnatal
mammalian isthmus.
AB - The isthmus is recognized as the most rostral segment of the hindbrain in non
mammalian vertebrates. In mammalian embryos, transient Fgf8 expression defines
the developing isthmic region, lying between the midbrain and the first
rhombomere, but there has been uncertainty about the existence of a distinct
isthmic segment in postnatal mammals. We attempted to find if the region of early
embryonic Fgf8 expression (which is considered to involve the entire extent of
the prospective isthmus initially) might help to identify the boundaries of the
isthmus in postnatal animals. By creating an Fgf8-Cre-LacZ lineage in mice, we
were able to show that Fgf8-Cre reporter expression in postnatal mice is present
in the same nuclei that characterize the isthmic region in birds. The 'signature'
isthmic structures in birds include the trochlear nucleus, the dorsal raphe
nucleus, the microcellular tegmental nuclei, the pedunculotegmental nucleus, the
vermis of the cerebellum, rostral parts of the parabrachial complex and locus
coeruleus, and the caudal parts of the substantia nigra and VTA. We found that
all of these structures were labeled with the Fgf8-Cre reporter in the mouse
brain, and we conclude that the isthmus is a distinct segment of the mammalian
brain lying caudal to the midbrain and rostral to rhombomere 1 of the hindbrain.
PMID- 28510271
TI - Application of Combination High-Throughput Phenotypic Screening and Target
Identification Methods for the Discovery of Natural Product-Based Combination
Drugs.
AB - Modern drug discovery efforts have had mediocre success rates with increasing
developmental costs, and this has encouraged pharmaceutical scientists to seek
innovative approaches. Recently with the rise of the fields of systems biology
and metabolomics, network pharmacology (NP) has begun to emerge as a new paradigm
in drug discovery, with a focus on multiple targets and drug combinations for
treating disease. Studies on the benefits of drug combinations lay the groundwork
for a renewed focus on natural products in drug discovery. Natural products
consist of a multitude of constituents that can act on a variety of targets in
the body to induce pharmacodynamic responses that may together culminate in an
additive or synergistic therapeutic effect. Although natural products cannot be
patented, they can be used as starting points in the discovery of potent
combination therapeutics. The optimal mix of bioactive ingredients in natural
products can be determined via phenotypic screening. The targets and molecular
mechanisms of action of these active ingredients can then be determined using
chemical proteomics, and by implementing a reverse pharmacokinetics approach.
This review article provides evidence supporting the potential benefits of
natural product-based combination drugs, and summarizes drug discovery methods
that can be applied to this class of drugs.
PMID- 28510272
TI - Diabetes mellitus is associated with increased acute kidney injury and 1-year
mortality after transcatheter aortic valve replacement: A meta-analysis.
AB - BACKGROUND: Diabetes mellitus (DM) is associated with adverse outcomes after
surgical aortic valve replacement. However, there are conflicting data on the
impact of DM on outcomes of transcatheter aortic valve replacement (TAVR).
HYPOTHESIS: DM is associated with poor outcomes after different cardiac
procedures. Therefore, DM can also be associated with poor outcomes after TAVR.
METHODS: We searched PubMed and Cochrane Central Register of Controlled Trials
for studies that evaluated outcomes after TAVR and stratified at least 1 of the
studied endpoints by DM status. The primary endpoint was all-cause mortality at 1
year. Secondary endpoints were early (up to 30 days) mortality, acute kidney
injury (AKI), cerebrovascular accident (CVA), major bleeding, and major vascular
complications. Pooled odds ratio (OR) and 95% confidence interval (CI) were
calculated using random effects models. RESULTS: We included 64 studies with a
total of 38 686 patients. DM was associated with significantly higher 1-year
mortality (OR: 1.14, 95% CI: 1.04-1.26, P = 0.008) and periprocedural AKI (OR:
1.28, 95% CI: 1.08-1.52, P = 0.004). On the other hand, there were no significant
differences between diabetics and nondiabetics in early mortality, CVAs, major
bleeding, or major vascular complications. CONCLUSIONS: DM is associated with
increased 1-year mortality and periprocedural AKI in patients undergoing TAVR.
The results of this study suggest that DM is a predictor of adverse outcomes in
patients undergoing TAVR.
PMID- 28510273
TI - Manganese-Catalyzed Sustainable Synthesis of Pyrroles from Alcohols and Amino
Alcohols.
AB - The development of reactions that convert alcohols into important chemical
compounds saves our fossil carbon resources as alcohols can be obtained from
indigestible biomass such as lignocellulose. The conservation of our rare noble
metals is of similar importance, and their replacement by abundantly available
transition metals, such as Mn, Fe, or Co (base or nonprecious metals), in key
technologies such as catalysis is a promising option. Herein, we report on the
first base-metal-catalyzed synthesis of pyrroles from alcohols and amino
alcohols. The most efficient catalysts are Mn complexes stabilized by PN5 P
ligands whereas related Fe and Co complexes are inactive. The reaction proceeds
under mild conditions at catalyst loadings as low as 0.5 mol %, and has a broad
scope and attractive functional-group tolerance. These findings may inspire
others to use Mn catalysts to replace Ir or Ru complexes in challenging
dehydrogenation reactions.
PMID- 28510269
TI - Kallikrein-related peptidase 4 induces cancer-associated fibroblast features in
prostate-derived stromal cells.
AB - The reciprocal communication between cancer cells and their microenvironment is
critical in cancer progression. Although involvement of cancer-associated
fibroblasts (CAF) in cancer progression is long established, the molecular
mechanisms leading to differentiation of CAFs from normal fibroblasts are poorly
understood. Here, we report that kallikrein-related peptidase-4 (KLK4) promotes
CAF differentiation. KLK4 is highly expressed in prostate epithelial cells of
premalignant (prostatic intraepithelial neoplasia) and malignant lesions compared
to normal prostate epithelia, especially at the peristromal interface. KLK4
induced CAF-like features in the prostate-derived WPMY1 normal stromal cell line,
including increased expression of alpha-smooth muscle actin, ESR1 and SFRP1. KLK4
activated protease-activated receptor-1 in WPMY1 cells increasing expression of
several factors (FGF1, TAGLN, LOX, IL8, VEGFA) involved in prostate cancer
progression. In addition, KLK4 induced WPMY1 cell proliferation and secretome
changes, which in turn stimulated HUVEC cell proliferation that could be blocked
by a VEGFA antibody. Importantly, the genes dysregulated by KLK4 treatment of
WPMY1 cells were also differentially expressed between patient-derived CAFs
compared to matched nonmalignant fibroblasts and were further increased by KLK4
treatment. Taken together, we propose that epithelial-derived KLK4 promotes
tumour progression by actively promoting CAF differentiation in the prostate
stromal microenvironment.
PMID- 28510274
TI - The effect of prazosin on outcome in feline urethral obstruction.
AB - OBJECTIVE: To determine whether prazosin administration following urethral
obstruction (UO) reduces the risk for recurrent urethral obstruction (rUO) or
lower urinary tract signs, and to document adverse effects associated with
prazosin use in cats. DESIGN: Double-blinded, prospective, interventional study.
SETTING: University teaching hospital. ANIMALS: A population of 47 consecutive
male cats with UO not associated with urinary tract calculi >2 mm in diameter.
INTERVENTIONS: Cats were randomized to receive either prazosin (0.25 mg/cat PO q
12 h, n = 27) or placebo (n = 20) for 1 month following UO. MEASUREMENTS AND MAIN
RESULTS: Cats were monitored for rUO, severity of lower urinary tract signs, and
medication adverse effects during hospitalization and through weekly
conversations with the owner during the 1- month study period and once more at 6
months following discharge. There was no difference in the rUO rate among cats
that received prazosin or placebo prior to hospital discharge (2/26 (7%) versus
1/19 (5%), P = 1.00), during the 1- month medication period (4/26 (15%) versus
3/18 (17%), P = 0.776), or at 6 months following treatment for UO (7/19 (37%)
versus 4/13 (31%), P = 0.811). There was no difference in the severity of lower
urinary tract signs reported by the owners at the 1-, 2-, 3-, or 4-week follow-up
periods among the cats in either group (P = 0.62, 0.68, 0.33, 1.00,
respectively). Reported adverse effects from prazosin administration included
lethargy, ptyalism, diarrhea, anorexia, and malodorous stool. CONCLUSIONS:
Although our study results failed to find a difference in the incidence of rUO
and severity of lower urinary tract signs among cats receiving prazosin and those
receiving placebo, these study results should be interpreted cautiously as our
study was underpowered to identify such differences. Larger placebo-controlled,
prospective studies are needed to determine the clinical utility of prazosin in
prevention of rUO.
PMID- 28510275
TI - Single cell transcriptome profiling of developing chick retinal cells.
AB - The vertebrate retina is a specialized photosensitive tissue comprised of six
neuronal and one glial cell types, each of which develops in prescribed
proportions at overlapping timepoints from a common progenitor pool. While each
of these cells has a specific function contributing to proper vision in the
mature animal, their differential representation in the retina as well as the
presence of distinctive cellular subtypes makes identifying the transcriptomic
signatures that lead to each retinal cell's fate determination and development
challenging. We have analyzed transcriptomes from individual cells isolated from
the chick retina throughout retinogenesis. While we focused our efforts on the
retinal ganglion cells, our transcriptomes of developing chick cells also
contained representation from multiple retinal cell types, including
photoreceptors and interneurons at different stages of development. Most
interesting was the identification of transcriptomes from individual mixed
lineage progenitor cells in the chick as these cells offer a window into the cell
fate decision-making process. Taken together, these data sets will enable us to
uncover the most critical genes acting in the steps of cell fate determination
and early differentiation of various retinal cell types.
PMID- 28510276
TI - Canine reticulocyte hemoglobin content (RET-He) in different types of iron
deficient erythropoiesis.
AB - BACKGROUND: Reticulocyte hemoglobin content (RET-He) is a diagnostic marker for
iron deficiency (ID) in people and dogs. OBJECTIVES: The aim of our study was to
evaluate the clinical utility of RET-He in the diagnosis of different causes of
iron-deficient erythropoiesis (IDE). METHODS: Canine CBCs were separated into 2
groups according to RET-He values, < 20.9 pg or >= 20.9 pg. Erythrocyte and
reticulocyte variables were compared between dogs with decreased and normal RET
He values. Additional data for a subgroup of dogs were collected, and dogs with
low RET-He values were categorized as having ID, inflammatory disorders (INFL),
portosystemic shunt (PSS), miscellaneous diseases (MISC), or combinations of
these diseases (ID+INFL, ID+PSS). Hematologic variables were compared between
dogs of the different disease groups. RESULTS: Overall, 10.3% (1084/10,553) of
canine CBCs showed decreased RET-He values. Significant differences between dogs
with decreased and normal RET-He values were found for all erythrocyte and
reticulocyte variables. The majority (68.9%, 747/1084) of dogs with low RET-He
values was anemic; 28.9% (216/747) of those anemic dogs had microcytosis and
hypochromasia. In the subgroup of dogs, 8.9% (205/2306) had low RET-He values.
According to their diagnosed diseases, anemic dogs (138/205) could be categorized
as ID (17/138; 12.3%), INFL (16/138; 11.6%), PSS (30/138; 21.7%), ID+INFL
(63/138; 45.7%), ID+PSS (8/138; 5.8%), and MISC (4/138; 2.9%). Distribution in
nonanemic dogs (67/205) was similar, except for a lower number of dogs with PSS.
CONCLUSIONS: Low RET-He values indicate IDE even in dogs with other CBC variables
within the RIs.
PMID- 28510277
TI - Analysis of cytotoxic effects of chlorhexidine gluconate as antiseptic agent on
human blood lymphocytes.
AB - The aim of this study was to assess the cytotoxicity of chlorhexidine gluconate
(CHG) on human blood lymphocytes as a useful ex vivo model for accelerated human
toxicity studies. Using biochemical and flow cytometry assessments, we
demonstrated that addition of CHG at 1 MUM concentration to human blood
lymphocytes induced cytotoxicity following 6 h. The CHG-induced cytotoxicity on
human blood lymphocytes was associated with intracellular reactive oxygen species
generation, mitochondrial membrane potential collapse, lysosomal membrane injury,
lipid peroxidation, and depletion of glutathione. According to our results, CHG
triggers oxidative stress and organelles damages in lymphocytes which are
important cells in defense against foreign agents. Finally our findings suggest
that using of antioxidants and mitochondrial/lysosomal protective agents could be
of benefit for the people in the exposure with CHG.
PMID- 28510279
TI - 1-Substituted 2-Azaspiro[3.3]heptanes: Overlooked Motifs for Drug Discovery.
AB - The 2-substituted piperidine core is found in drugs (18 FDA-approved drugs),
however, their spirocyclic analogues remain unknown. Described here is the
synthesis of spirocyclic analogues for 2-substituted piperidines and a
demonstration of their validation in drug discovery.
PMID- 28510278
TI - TFG-MET fusion in an infantile spindle cell sarcoma with neural features.
AB - An increasing number of congenital and infantile sarcomas displaying a primitive,
monomorphic spindle cell phenotype have been characterized to harbor recurrent
gene fusions, including infantile fibrosarcoma and congenital spindle cell
rhabdomyosarcoma. Here, we report an unusual spindle cell sarcoma presenting as a
large and infiltrative pelvic soft tissue mass in a 4-month-old girl, which
revealed a novel TFG-MET gene fusion by whole transcriptome RNA sequencing. The
tumor resembled the morphology of an infantile fibrosarcoma with both fascicular
and patternless growth, however, it expressed strong S100 protein
immunoreactivity, while lacking SOX10 staining and retaining H3K27me3 expression.
Although this immunoprofile suggested partial neural/neuroectodermal
differentiation, overall features were unusual and did not fit into any known
tumor types (cellular schwannoma, MPNST), raising the possibility of a novel
pathologic entity. The TFG-MET gene fusion expands the genetic spectrum
implicated in the pathogenesis of congenital spindle cell sarcomas, with yet
another example of kinase oncogenic activation through chromosomal translocation.
The discovery of this new fusion is significant since the resulting MET
activation can potentially be inhibited by targeted therapy, as MET inhibitors
are presently available in clinical trials.
PMID- 28510281
TI - CuI/Oxalic Diamide-Catalyzed Cross-Coupling of Thiols with Aryl Bromides and
Chlorides.
AB - We report a general copper-catalyzed cross-coupling of thiols with aryl halides
by using N-aryl-N'-alkyl oxalic diamide (L3) or N,N'-dialkyl oxalic diamide (L5)
as the ligand. Both aryl and alkyl thiols can be coupled with unactivated aryl
bromides and chlorides to give the desired products in good yields. Furthermore,
this system features a broad substrate scope and good tolerance of functional
groups. Importantly, the oxalic diamides are stable and can be prepared easily
from commercially available and cheap starting materials.
PMID- 28510280
TI - Modeling the Iatrogenic Pancreatic Cancer Risk After Islet Autotransplantation in
Mouse.
AB - Iatrogenic pancreatic cancer metastasis after islet infusion is a potential risk
of islet autotransplantation performed after pancreatectomy. To model this risk,
islets and/or pancreatic exocrine clusters obtained from a genetically engineered
mouse model for pancreatic ductal adenocarcinoma (the LSL-KrasG12D/+ ;LSL
Trp53R172H/+ ;Pdx-1-Cre, termed KPC mouse) were transplanted via the portal vein
in syngeneic wild type (WT) severely diabetic recipients in the following
treatment groups: group A (n = 11) received KPC exocrine clusters in volume equal
to 250 islet equivalents (IEQs); group B (n = 12) received 250 WT IEQs mixed with
KPC exocrine clusters (1:1 volume ratio); group C (n = 5) received 250 KPC IEQs,
and group D (n = 7) received 250 WT IEQs. The incidence of hepatic metastasis was
assessed by magnetic resonance imaging and histology over the 13 months of follow
up. Overall survival was not different in the four groups. No mice developed
liver metastases during the follow-up. Two mice developed spontaneous tumors: a
liver hepatocellular tumor in group A and a malignant lymphoma in group D. Islets
and/or exocrine clusters obtained by KPC mouse, a model that develops pancreatic
cancer with 100% penetrance, do not retain the same risk of tumor development
when transplanted via the portal vein in a syngeneic diabetic recipient.
PMID- 28510282
TI - Cytologic features of a feline inductive odontogenic tumor.
AB - The feline inductive odontogenic tumor (FIOT) is a rare entity among oral tumors
in cats, the cytologic features of which are not well characterized but may prove
useful. A fine-needle aspiration biopsy was performed on the right mandible
between the permanent canine (404) and permanent fourth premolar (408) of an 8
month-old female mongrel cat. Cytologic smears showed epithelial cells and
occasional spindle cells with extracellular homogenous acidophilic material in a
hematic background. The initial diagnosis of benign tumor was confirmed by
histopathologic examination of the biopsy specimen. This report describes the
cytologic findings in a case of FIOT.
PMID- 28510283
TI - Ca2+ -Cl- Association in Water Revisited: the Role of Cation Hydration.
AB - We investigate the dissociation of a Ca2+ -Cl- pair in water using classical
molecular dynamics simulations with a polarizable interaction potential,
parameterized from ab initio calculations. By computing the potential of mean
force as a function not only of the interionic distance but also of the
coordination numbers by water molecules, we show that it is necessary to use a
collective variable describing the cation hydration in order to capture the
dissociation mechanism. In the contact ion pair, the Ca2+ cation has a first
coordination sphere containing 5 or 6 water molecules. The minimum free-energy
path for dissociation involves a two-step process: First one or two additional
water molecules enter the cation coordination shell, increasing the coordination
number up to 7 with an almost fixed interionic distance. Then the dissociation of
the ionic pair occurs at this fixed coordination number.
PMID- 28510284
TI - Tricyanomethane and Its Ketenimine Tautomer: Generation from Different Precursors
and Analysis in Solution, Argon Matrix, and as a Single Crystal.
AB - Solutions of azidomethylidenemalononitrile were photolyzed at low temperatures to
produce the corresponding 2H-azirine and tricyanomethane, which were analyzed by
low-temperature NMR spectroscopy. The latter product was also observed after
short thermolysis of the azide precursor in solution whereas irradiation of the
azide isolated in an argon matrix did not lead to tricyanomethane, but to
unequivocal detection of the tautomeric ketenimine by IR spectroscopy for the
first time. When the long-known "aquoethereal" greenish phase generated from
potassium tricyanomethanide, dilute sulfuric acid, and diethyl ether was rapidly
evaporated and sublimed, a mixture of hydronium tricyanomethanide and
tricyanomethane was formed instead of the previously claimed ketenimine tautomer.
Under special conditions of sublimation, single crystals of tricyanomethane could
be isolated, which enabled the analysis of the molecular structure by X-ray
diffraction.
PMID- 28510285
TI - Influence of quality of recovery on patient satisfaction with anaesthesia and
surgery: a prospective observational cohort study.
AB - Patient satisfaction and quality of recovery are important measures of quality.
Whether, and to what extent, patient satisfaction is influenced by quality of
recovery, however, is not clear. The aim of this study was to evaluate the
additional influence of quality of recovery on total patient satisfaction with
anaesthesia and surgery. In this prospective cohort study, we used a validated
quality of recovery questionnaire and a multi-item patient satisfaction
questionnaire. Patients completed the quality of recovery questionnaire pre
operatively and 24 h postoperatively. One to two weeks after discharge, a third
quality of recovery questionnaire was sent out, together with the patient
satisfaction questionnaire. If no response was received after 2 weeks, a reminder
containing the quality of recovery and the satisfaction questionnaire were
mailed. Seven hundred and thirty-four patients were consecutively assessed for
eligibility. Five hundred and seventy-nine patients completed at least one
questionnaire (recruitment rate 79%). Four hundred and sixty-seven patients (81%)
completed all four questionnaires. The total satisfaction score was high, with a
mean (SD) of 94.6 (10.7) on a 0-100 scale. Correlation analysis between quality
of recovery and total patient satisfaction showed correlations of 0.2-0.3.
Testing different aspects of quality of recovery in models already containing the
significant factors of patient satisfaction did not improve the model fit
markedly. We conclude that quality of recovery has only a marginal additional
effect on total patient satisfaction with anaesthesia and surgery.
PMID- 28510286
TI - An Enyne Cope Rearrangement Enables Polycycloalkane Synthesis from Readily
Available Starting Materials.
AB - Cyclohexanone-derived Knoevenagel adducts (cyclohexylidenemalononitriles) and two
different propargyl electrophiles serve as carbon sources for assembling diverse
6/7/5 tricycloalkanes, a common terpenoid framework. The sequence involves three
unique reactions: 1) deconjugative propargylation, 2) one-pot enyne Cope
rearrangement/deconjugative propargylation, and 3) an allenic Pauson-Khand
reaction.
PMID- 28510287
TI - A Dual Palladium and Copper Hydride Catalyzed Approach for Alkyl-Aryl Cross
Coupling of Aryl Halides and Olefins.
AB - We report an efficient means of sp2 -sp3 cross coupling for a variety of terminal
monosubstituted olefins with aryl electrophiles using Pd and CuH catalysis. In
addition to its applicability to a range of aryl bromide substrates, this process
was also suitable for electron-deficient aryl chlorides, furnishing higher yields
than the corresponding aryl bromides in these cases. The optimized protocol does
not require the use of a glovebox and employs air-stable Cu and Pd complexes as
precatalysts. A reaction on 10 mmol scale further highlighted the practical
utility of this protocol. Employing a similar protocol, a series of cyclic
alkenes were also examined. Cyclopentene was shown to undergo efficient coupling
under these conditions. Lastly, deuterium-labeling studies indicate that
deuterium scrambling does not take place in this sp2 -sp3 cross coupling,
implying that beta-hydride elimination is not a significant process in this
transformation.
PMID- 28510288
TI - The Relationship of Physiopsychosocial Factors and Spiritual Well-Being in
Elderly Residents: Implications for Evidence-Based Practice.
AB - BACKGROUND: Older adults in residential settings frequently suffer from
functional decline, mental illness, and social isolation, which make them more
vulnerable to spiritual distress. However, empirical evidence of the
interrelationships between physiopsychosocial variables and spiritual well-being
are still lacking, limiting the application of the biopsychosocial-spiritual
model in institutional healthcare practice. AIMS: To explain the mechanisms by
which these variables are linked, this cross-sectional study tested a causal
model of predictors of spiritual well-being among 377 institutionalized older
adults with disability using a structural equation modeling approach. METHODS:
The primary variables in the hypothesized model were measured using the Barthel
Index for functional ability, the Geriatric Depression Scale-short form for
depression, the Personal Resources Questionnaire 85-Part 2 for perceived social
support, and the Spiritual Well-Being Scale for spiritual well-being. RESULTS:
The model fit indices suggest that the hypothesized model had a reasonably
adequate model fit (chi2 = 12.18, df = 6, p = .07, goodness-of-fitness index
[GFI] = 0.99, adjusted GIF index [AGFI] = 0.93, nonnormed fit index [NFI] = 0.99,
comparative fit index [CFI] = 0.99). In this study, perceived social support and
depression directly affected spiritual well-being, and functional ability
indirectly affected spiritual well-being via perceived social support or
depression. In addition, functional ability influenced perceived social support
directly, which in turn influenced depression and ultimately influenced spiritual
well-being. DISCUSSION: This study results confirm the effect of
physiopsychosocial factors on institutionalized older adults' spiritual well
being. However, the presence and level of functional disability do not
necessarily influence spiritual well-being in late life unless it is disruptive
to social relationships and is thus bound to lead to low perceived social support
and the onset of depression. LINKING EVIDENCE TO ACTION: The findings address the
fact that the practice of spirituality is multidimensional and multileveled.
Psychosocial interventions for institutionalized elders with disabilities should
focus on increasing nurse-patient interaction and providing access to meaningful
social activities to improve mental health and spiritual well-being.
PMID- 28510289
TI - Genome organization during the cell cycle: unity in division.
AB - During the cell cycle, the genome must undergo dramatic changes in structure,
from a decondensed, yet highly organized interphase structure to a condensed,
generic mitotic chromosome and then back again. For faithful cell division, the
genome must be replicated and chromosomes and sister chromatids physically
segregated from one another. Throughout these processes, there is feedback and
tension between the information-storing role and the physical properties of
chromosomes. With a combination of recent techniques in fluorescence microscopy,
chromosome conformation capture (Hi-C), biophysical experiments, and
computational modeling, we can now attribute mechanisms to many long-observed
features of chromosome structure changes during cell division. Apparent conflicts
that arise when integrating the concepts from these different proposed mechanisms
emphasize that orchestrating chromosome organization during cell division
requires a complex system of factors rather than a simple pathway. Cell division
is both essential for and threatening to proper genome organization. As
interphase three-dimensional (3D) genome structure is quite static at a global
level, cell division provides an important window of opportunity to make
substantial changes in 3D genome organization in daughter cells, allowing for
proper differentiation and development. Mistakes in the process of chromosome
condensation or rebuilding the structure after mitosis can lead to diseases such
as cancer, premature aging, and neurodegeneration. WIREs Syst Biol Med 2017,
9:e1389. doi: 10.1002/wsbm.1389 For further resources related to this article,
please visit the WIREs website.
PMID- 28510290
TI - Retrospective evaluation of the impact of early enteral nutrition on clinical
outcomes in dogs with pancreatitis: 34 cases (2010-2013).
AB - OBJECTIVE: To evaluate the effect of early enteral nutritional therapy on time to
return to voluntary intake, maximum food consumption, incidence of
gastrointestinal intolerance (GI), and total hospitalization time for dogs with
acute pancreatitis. DESIGN AND SETTING: Retrospective analysis of dogs with
pancreatitis at a veterinary teaching hospital between 2010 and 2013. ANIMALS:
Thirty-four client-owned dogs diagnosed with acute or acute-on-chronic
pancreatitis. PROCEDURES AND INTERVENTIONS: Medical records of dogs evaluated for
inappetence, anorexia, and GI for which a diagnosis of pancreatitis was recorded
were reviewed. The time to initiation of food offerings since hospitalization
were recorded in addition to signalment, historical medical conditions, chief
complaint, physical examination findings, diagnostic results, treatments
provided, timing of food offering (within 48 h of hospitalization, early feeding
group (EFG) versus delayed feeding group (DFG), diet therapy (low fat versus high
fat), caloric intake (% resting energy requirement), incidence of GI (%), and
length of hospitalization (LOH) (days). A Clinical Severity Index Score (CSIS)
was determined for each patient. MEASUREMENTS AND MAIN RESULTS: Dogs in the EFG
demonstrated a decreased time to return of voluntary intake (2.1 days, EFG versus
2.7 days, DFG; P = 0.05) and time (days) to maximum intake (3, EFG versus 3.4
DFG) as compared to the DFG dogs. The DFG exhibited more GI versus EFG
irrespective of CSIS grouping (60% versus 26%, P = 0.04). A CSIS >= 7 was
associated with prolonged LOH (P = 0.004); however, time to initiation of feeding
and diet selection did not impact LOH (P = 0.8). CONCLUSIONS AND CLINICAL
RELEVANCE: Results of the study suggested that feeding within 48 hours of
hospitalization for canine pancreatitis has a positive impact on return to
voluntary intake and decreases the frequency of GI in these patients, independent
of CSIS. The traditional protocol of withholding food during hospitalization may
not be necessary nor yield the most benefit for patient recovery; subsequently
early enteral refeeding should be considered.
PMID- 28510292
TI - Enhanced Photoelectrochemical Activity by Autologous Cd/CdO/CdS Heterojunction
Photoanodes with High Conductivity and Separation Efficiency.
AB - The development for hydrogen from solar energy has attracted great attention due
to the global demand for clean, environmentally friendly energy. Herein,
autologous Cd/CdO/CdS heterojunctions were prepared in a carefully controlled
process with metallic Cd as the inner layer and CdO as the interlayer. Further
research revealed that the transportation and separation of photogenerated pairs
were enhanced due to low resistance of the Cd inner layer and the type II CdO/CdS
heterojunction. As a result, the optimized Cd/CdO/CdS heterojunction photoanode
showed outstanding and long-term photoelectrochemical activity for water
splitting, with a current density of 3.52 mA cm-2 , or a benchmark specific
hydrogen production rate of 1.65 MUmol cm-2 min-1 at -0.3 V versus Ag/AgCl, by
using the environmental pollutants of sulfide and sulfite as sacrificial agents.
PMID- 28510293
TI - A test for Y-linked additive and epistatic effects on surviving bacterial
infections in Drosophila melanogaster.
AB - Y- and W-chromosomes offer a theoretically powerful way for sexual dimorphism to
evolve. Consistent with this possibility, Drosophila melanogaster Y-chromosomes
can influence gene regulation throughout the genome; particularly immune-related
genes. In order for Y-linked regulatory variation (YRV) to contribute to adaptive
evolution it must be comprised of additive genetic variance, such that variable
Ys induce consistent phenotypic effects within the local gene pool. We assessed
the potential for Y-chromosomes to adaptively shape gram-negative and gram
positive bacterial defence by introgressing Ys across multiple genetic haplotypes
from the same population. We found no Y-linked additive effects on immune
phenotypes, suggesting a restricted role for the Y to facilitate dimorphic
evolution. We did find, however, a large magnitude Y by background interaction
that induced rank order reversals of Y-effects across the backgrounds (i.e. sign
epistasis). Thus, Y-chromosome effects appeared consistent within backgrounds,
but highly variable among backgrounds. This large sign epistatic effect could
constrain monomorphic selection in both sexes, considering that autosomal alleles
under selection must spend half of their time in a male background where relative
fitness values are altered. If the pattern described here is consistent for other
traits or within other XY (or ZW) systems, then YRV may represent a universal
constraint to autosomal trait evolution.
PMID- 28510294
TI - Dual photon microscopy based quantitation of fibrosis-related parameters (q-FP)
to model disease progression in steatohepatitis: Methodological issues.
PMID- 28510291
TI - Associations between RNA splicing regulatory variants of stemness-related genes
and racial disparities in susceptibility to prostate cancer.
AB - Evidence suggests that cells with a stemness phenotype play a pivotal role in
oncogenesis, and prostate cells exhibiting this phenotype have been identified.
We used two genome-wide association study (GWAS) datasets of African descendants,
from the Multiethnic/Minority Cohort Study of Diet and Cancer (MEC) and the Ghana
Prostate Study, and two GWAS datasets of non-Hispanic whites, from the Prostate,
Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and the Breast and
Prostate Cancer Cohort Consortium (BPC3), to analyze the associations between
genetic variants of stemness-related genes and racial disparities in
susceptibility to prostate cancer. We evaluated associations of single-nucleotide
polymorphisms (SNPs) in 25 stemness-related genes with prostate cancer risk in
1,609 cases and 2,550 controls of non-Hispanic whites (4,934 SNPs) and 1,144
cases and 1,116 controls of African descendants (5,448 SNPs) with correction by
false discovery rate <=0.2. We identified 32 SNPs in five genes (TP63, ALDH1A1,
WNT1, MET and EGFR) that were significantly associated with prostate cancer risk,
of which six SNPs in three genes (TP63, ALDH1A1 and WNT1) and eight EGFR SNPs
showed heterogeneity in susceptibility between these two racial groups. In
addition, 13 SNPs in MET and one in ALDH1A1 were found only in African
descendants. The in silico bioinformatics analyses revealed that EGFR rs2072454
and SNPs in linkage with the identified SNPs in MET and ALDH1A1 (r2 > 0.6) were
predicted to regulate RNA splicing. These variants may serve as novel biomarkers
for racial disparities in prostate cancer risk.
PMID- 28510295
TI - Scandium-Mediated Formation of a Bis(tetrahydropentalene).
AB - The reactivity of Li[Sc(COT'')2 ] (1; COT''=1,4
bis(trimethylsilyl)cyclooctatetraenyl) towards CoCl2 is considerably different
from that of related lanthanide triple-decker sandwich complexes. In addition to
the expected triple-decker complex Sc2 (COT'')3 (2), the complex Sc2 {MU
BTHP}(COT'')2 (3) is formed, which comprises the novel BTHP2- ligand (BTHP2-
=bis(3,5-bis(trimethylsilyl)-1,3a,6,6a-tetrahydropentalene-1-yl)diide or bis(2,7
bis(trimethylsilyl)bicyclo[3.3.0]octa-2,7-dien-4-yl)diide, C16 H10 (SiMe3 )42- ).
The formation of 3 is likely facilitated by the fact that scandium prefers eta8
,eta3 coordination rather than highly symmetric eta8 ,eta8 coordination, and
the eta3 -coordinated COT'' ligand in 1 is activated owing to a loss of
aromaticity. Acid hydrolysis of 3 leads to air-stable H2 BTHP (4).
PMID- 28510296
TI - Pharmacokinetics and Safety of Single-Dose Inhaled Loxapine in Children and
Adolescents.
AB - This multisite open-label study sought to characterize the pharmacokinetics and
safety of a single dose of inhaled loxapine in children and adolescents. Loxapine
powder for oral inhalation was administered via a single-use handheld drug device
to children and adolescents (aged 10-17 years) with any condition warranting
chronic antipsychotic use. Patients were dosed according to body weight and
cohort (<50 kg [n = 15], 2.5 or 5 mg; >=50 kg [n = 15], 5 or 10 mg); the first 6
patients (cohort 1) enrolled in each weight group received the lower dose.
Patients were enrolled in the higher-dose group (cohort 2) after an interim
pharmacokinetic and safety analysis of data from cohort 1. Blood samples were
collected for 48 hours after dosing to determine the pharmacokinetic profile of
loxapine and its metabolites. Safety was assessed using adverse event (AE),
laboratory value, physical/neurologic examination, vital sign, electrocardiogram,
suicidality, and extrapyramidal symptom assessment. Thirty patients were enrolled
and evaluable for pharmacokinetics. Loxapine plasma concentrations peaked by 2 to
5 minutes in most patients; systemic exposure increased with dose in both weight
subgroups. Loxapine terminal elimination half-life was ~13 to 17 hours. The most
common AEs were sedation and dysgeusia. Sedation was severe in 1 patient in the
<50-kg group (2.5-mg dose) and 1 patient in the >=50-kg group (5-mg dose). No AEs
indicative of bronchospasm or other serious AEs were reported. Inhaled loxapine
was rapidly absorbed and generally well tolerated in pediatric patients; no new
safety signals were observed.
PMID- 28510298
TI - Drugs for Children.
AB - The "Therapeutic Orphan" status of children is gradually improving, but our
efforts to eliminate off-label/off-evidence use must be sustained for safer and
more effective pediatric drug therapy. This is even more important in resource
scarce settings, because of the increasing child population in those regions. The
juncture of pediatric pharmacology and global child health represents an emerging
field of clinical pharmacology illuminating a crucial societal need on a global
scale.
PMID- 28510297
TI - Evaluation of the Safety of Drugs and Biological Products Used During Lactation:
Workshop Summary.
AB - This report serves as a summary of a 2-day public workshop sponsored by the US
Food and Drug Administration (FDA) to discuss the safety of drugs and biological
products used during lactation. The aim of the workshop was to provide a forum to
discuss the collection of data to inform the potential risks to breastfed infants
with maternal use of medications during lactation. Discussions included the
review of current approaches to collect data on medications used during
lactation, and the considerations for future approaches to design and guide
clinical lactation studies. This workshop is part of continuing efforts to raise
the awareness of the public for women who choose to breastfeed their infants.
PMID- 28510302
TI - Association study of genetic variation in DNA repair pathway genes and risk of
basal cell carcinoma.
AB - DNA repair plays a critical role in protecting the genome from ultraviolet
radiation and maintaining the genomic integrity of cells. Genetic variants in DNA
repair-related genes can influence an individual's DNA repair capacity, which may
be related to the risk of developing basal cell carcinoma (BCC). We
comprehensively assessed the associations of 2,965 independent single-nucleotide
polymorphisms (SNPs) across 165 DNA repair pathway genes with BCC risk in a
genome-wide association meta-analysis totaling 17,187 BCC cases and 287,054
controls from two data sets. After multiple testing corrections, we identified
three SNPs (rs2805831 upstream of XPA: OR = 0.93, P = 1.35 * 10-6 ; rs659857 in
exon of MUS81: OR = 1.06, P = 3.09 * 10-6 and rs57343616 in 3' UTR of NABP2: OR =
1.11, P = 6.47 * 10-6 ) as significantly associated with BCC risk in meta
analysis, and all of them were nominally significant in both data sets.
Furthermore, rs659857 [T] was significantly associated with decreased expression
of MUS81 mRNA in the expression quantitative trait locus (eQTL) analysis. Our
findings suggest that the inherited common variation in three DNA repair genes
XPA, MUS81 and NABP2-may be involved in the development of BCC. To our knowledge,
our study is the first report thoroughly examining the effects of SNPs across DNA
repair pathway genes on BCC risk based on a genome-wide association meta
analysis.
PMID- 28510304
TI - Flip-Flop Phenomenon in Epidural Sufentanil Pharmacokinetics: A Population Study
in Children and Infants.
AB - The aims of this study were to develop a population pharmacokinetic model of
sufentanil coadministered with 0.2% ropivacaine as an epidural infusion in
infants and describe the sufentanil absorption profile from epidural space. Data
from 2 previously published studies were merged for analysis-20 infants aged 3-36
months receiving sufentanil as an epidural infusion and 41 children 0-17 years
old receiving sufentanil as a long-term intravenous infusion. A population
nonlinear mixed-effects model was built in NONMEM. Sufentanil pharmacokinetics
were described by a 2-compartment model with first-order absorption. The effect
of body size on all volume and clearance parameters was included in the model
according to allometric scaling with theoretical exponents. The maturation
process of metabolic clearance was described by the Hill model. During the model
building process the population was divided into 2 fractions with different
typical values of metabolic clearance (CL1 and CL2). The typical values of
systemic clearance scaled to a 70-kg patient for the 2 subpopulations were CL1 =
52.6 L/h and CL2 = 158 L/h. The parameters of the Hill function were 54.9 weeks
for the postmenstrual age of 50% clearance maturation and 0.802 for the Hill
coefficient. The typical values of distribution clearance and volumes of the
central and peripheral compartments for a patient with a weight of 70 kg were Q =
40.5 L/h, VC = 7.63 L, and VT = 473 L, respectively. The value of the absorption
rate constant from the epidural space was 0.0459/h, which suggests flip-flop
pharmacokinetics of sufentanil after epidural administration.
PMID- 28510303
TI - A Binary Bivalent Supramolecular Assembly Platform Based on Cucurbit[8]uril and
Dimeric Adapter Protein 14-3-3.
AB - Interactions between proteins frequently involve recognition sequences based on
multivalent binding events. Dimeric 14-3-3 adapter proteins are a prominent
example and typically bind partner proteins in a phosphorylation-dependent mono-
or bivalent manner. Herein we describe the development of a cucurbit[8]uril (Q8)
based supramolecular system, which in conjunction with the 14-3-3 protein dimer
acts as a binary and bivalent protein assembly platform. We fused the
phenylalanine-glycine-glycine (FGG) tripeptide motif to the N-terminus of the 14
3-3-binding epitope of the estrogen receptor alpha (ERalpha) for selective
binding to Q8. Q8-induced dimerization of the ERalpha epitope augmented its
affinity towards 14-3-3 through a binary bivalent binding mode. The crystal
structure of the Q8-induced ternary complex revealed molecular insight into the
multiple supramolecular interactions between the protein, the peptide, and Q8.
PMID- 28510305
TI - Reactive Precipitation of Anhydrous Alkali Sulfide Nanocrystals with Concomitant
Abatement of Hydrogen Sulfide and Cogeneration of Hydrogen.
AB - Anhydrous alkali sulfide (M2 S, M=Li or Na) nanocrystals (NCs) are important
materials central to the development of next generation cathodes and solid-state
electrolytes for advanced batteries, but not commercially available at present.
This work reports an innovative method to directly synthesize M2 S NCs through
alcohol-mediated reactions between alkali metals and hydrogen sulfide (H2 S). In
the first step, the alkali metal is complexed with alcohol in solution, forming
metal alkoxide (ROM) and releasing hydrogen (H2 ). Next, H2 S is bubbled through
the ROM solution, where both chemicals are completely consumed to produce phase
pure M2 S NC precipitates and regenerate alcohol that can be recycled. The M2 S
NCs morphology may be tuned through the choice of the alcohol and solvent. Both
synthetic steps are thermodynamically favorable (DeltaGmo <-100 kJ mol-1 ),
proceeding rapidly to completion at ambient temperature with almost 100 % atom
efficiency. The net result, H2 S+2 m->M2 S+H2 , makes good use of a hazardous
chemical (H2 S) and delivers two value-added products that naturally phase
separate for easy recovery. This scalable approach provides an energy-efficient
and environmentally benign solution to the production of nanostructured materials
required in emerging battery technologies.
PMID- 28510307
TI - Expansion and intensification of humoral autoimmune response in the transition
from preclinical to full-blown primary biliary cholangitis.
PMID- 28510306
TI - A polymorphism in miR-1262 regulatory region confers the risk of lung cancer in
Chinese population.
AB - It has been proposed that the majority of disease-associated loci identified by
genome-wide association studies (GWAS) are enriched in non-coding regions, such
as the promoter, enhancer or non-coding RNA genes. Thus, we performed a two-stage
case-control study to systematically evaluate the association of genetic variants
in miRNA regulatory regions (promoter and enhancer) with lung cancer risk in
7,763 subjects (discovery stage: 2,331 cases and 3,077 controls; validation
stage: 1,065 cases and 1,290 controls). As a result, we identified that
rs12740674 (C > T) in miR-1262 enhancer was significantly associated with the
increased risk of lung cancer (additive model in discovery stage: adjusted OR =
1.31, 95%CI = 1.13-1.53, p = 3.846 * 10-4 in Nanjing GWAS; adjusted OR = 1.20,
95%CI = 1.00-1.44, p = 0.041 in Beijing GWAS; validation stage: adjusted OR =
1.20, 95%CI = 1.03-1.41, p = 0.024). In meta-analysis, the p value for the
association between rs12740674 and lung cancer risk reached 6.204 * 10-6
(adjusted OR = 1.24, 95%CI = 1.13-1.36). Using 3DSNP database, The Cancer Genome
Atlas (TCGA) data and functional assays, we observed that the risk T allele of
rs12740674 reduced the expression level of miR-1262 in lung tissue through
chromosomal looping, and overexpression of miR-1262 inhibited lung cancer cell
proliferation probably through targeting the expression levels of ULK1 and RAB3D.
Our findings confirmed the important role that genetic variants of noncoding
sequence play in lung cancer susceptibility and indicated that rs12740674 in miR
1262 may be biologically relevant to lung carcinogenesis.
PMID- 28510308
TI - Satisfaction is not substantially affected by quality of recovery: different
constructs or are we lost in statistics?
PMID- 28510309
TI - Molecular classification of hepatoblastoma and prognostic value of the HB 16-gene
signature.
PMID- 28510310
TI - Anal fistula height: is the proportion of sphincteric muscle involved really
useful?
PMID- 28510311
TI - Rapid Microfluidic Dilution for Single-Molecule Spectroscopy of Low-Affinity
Biomolecular Complexes.
AB - To enable the investigation of low-affinity biomolecular complexes with confocal
single-molecule spectroscopy, we have developed a microfluidic device that allows
a concentrated sample to be diluted by up to five orders of magnitude within
milliseconds, at the physical limit dictated by diffusion. We demonstrate the
capabilities of the device by studying the dissociation kinetics and structural
properties of low-affinity protein complexes using single-molecule two-color and
three-color Forster resonance energy transfer (FRET). We show that the
versatility of the device makes it suitable for studying complexes with
dissociation constants from low nanomolar up to 10 MUm, thus covering a wide
range of biomolecular interactions. The design and precise fabrication of the
devices ensure simple yet reliable operation and high reproducibility of the
results.
PMID- 28510313
TI - Categorization and theoretical comparison of quantitative methods for assessing
QT/RR hysteresis.
AB - BACKGROUND: In the human electrocardiogram, there is a lag of adaptation of the
QT interval to heart rate changes, usually termed QT/RR hysteresis (QT-hys).
Subject-specific quantifiers of QT-hys have been proposed as potential
biomarkers, but there is no consensus on the choice of the quantifier. METHODS: A
comprehensive literature search was conducted to identify original articles
reporting quantifiers of repolarization hysteresis from the surface ECG in
humans. RESULTS: Sixty articles fulfilled our inclusion criteria. Reported
biomarkers were grouped under four categories. A simple mathematical model of
QT/RR loop was used to illustrate differences between the methods. Category I
quantifiers use direct measurement of QT time course of adaptation. They are
limited to conditions where RR intervals are under strict control. Category IIa
and IIb quantifiers compare QT responses during consecutive heart rate
acceleration and deceleration. They are relevant when a QT/RR loop is observed,
typically during exercise and recovery, but are not robust to protocol
variations. Category III quantifiers evaluate the optimum RR memory in dynamic
QT/RR relationship modeling. They estimate an intrinsic memory parameter
independent from the nature of RR changes, but their reliability remains to be
confirmed when multiple memory parameters are estimated. Promising approaches
include the differentiation of short-term and long-term memory and adaptive
estimation of memory parameters. CONCLUSION: Model-based approaches to QT-hys
assessment appear to be the most versatile, as they allow separate quantification
of QT/RR dependency and QT-hys, and can be applied to a wide range of
experimental settings.
PMID- 28510312
TI - The midbrain-to-pons ratio distinguishes progressive supranuclear palsy from non
fluent primary progressive aphasias.
AB - BACKGROUND AND PURPOSE: To determine the clinical utility of the midbrain-to-pons
(M/P) ratio as a clinical biomarker of progressive supranuclear palsy (PSP) in
patients with non-fluent primary progressive aphasia syndromes. METHODS: Patients
with PSP, progressive non-fluent aphasia (PNFA) and logopenic progressive aphasia
(LPA) were recruited. Patients were diagnosed clinically, but pathological
confirmation was available in a proportion of patients. Midbrain and pons areas
were measured using Osirix Lite, a free DICOM viewer. The M/P ratio and Magnetic
Resonance Parkinsonism Index were calculated and their diagnostic utility
compared. RESULTS: A total of 72 participants were included (16 PSP, 18 PNFA, 16
LPA and 22 controls). Patients with PSP had motor features typical of the
syndrome. Both the M/P ratio and Magnetic Resonance Parkinsonism Index differed
significantly in PSP compared with controls. The M/P ratio was disproportionately
reduced in PSP compared with PNFA and LPA (PSP, 0.182 +/- 0.043; PNFA, 0.255 +/-
0.034; LPA, 0.258 +/- 0.033; controls, 0.292 +/- 0.031; P < 0.001). An M/P ratio
of <=0.215 produced a positive predictive value of 77.8% for the diagnosis of PSP
syndrome. Pathological examination revealed Alzheimer's disease in three cases
(all LPA), pathological PSP in two cases (one clinical PSP and one PNFA) and
corticobasal degeneration in one case (PNFA). The M/P ratio was <=0.215 in both
pathological cases of PSP. CONCLUSIONS: The M/P ratio was disproportionately
reduced in PSP, suggesting its potential as a clinical marker of the PSP
syndrome. Larger studies of pathologically confirmed cases are needed to
establish the M/P ratio as a biomarker of PSP pathology.
PMID- 28510315
TI - BK Virus Nephropathy Revisited.
PMID- 28510314
TI - A Photoswitchable Dualsteric Ligand Controlling Receptor Efficacy.
AB - The investigation of the mode and time course of the activation of G-protein
coupled receptors (GPCRs), in particular muscarinic acetylcholine (mACh or M)
receptors, is still in its infancy despite the tremendous therapeutic relevance
of M receptors and GPCRs in general. We herein made use of a dualsteric ligand
that can concomitantly interact with the orthosteric, that is, the
neurotransmitter, binding site and an allosteric one. We synthetically
incorporated a photoswitchable (photochromic) azobenzene moiety. We characterized
the photophysical properties of this ligand called BQCAAI and investigated its
applicability as a pharmacological tool compound with a set of FRET techniques at
the M1 receptor. BQCAAI proved to be an unprecedented molecular tool; it is the
first photoswitchable dualsteric ligand, and its activity can be regulated by
light. We also applied BQCCAI to investigate the time course of several receptor
activation processes.
PMID- 28510316
TI - Laparoscopic en bloc total mesorectal excision post chemoradiotherapy - a video
vignette.
PMID- 28510317
TI - Efflux Pumps Might Not Be the Major Drivers of QAC Resistance in Methicillin
Resistant Staphylococcus aureus.
AB - Quaternary ammonium compounds (QACs) are commonly used antiseptics that are now
known to be subject to bacterial resistance. The prevalence and mechanisms of
such resistance, however, remain underexplored. We investigated a variety of
QACs, including those with multicationic structures (multiQACs), and the
resistance displayed by a variety of Staphylococcus aureus strains with and
without genes encoding efflux pumps, the purported main driver of bacterial
resistance in MRSA. Through minimum inhibitory concentration (MIC)-, kinetic-,
and efflux-based assays, we found that neither the qacR/qacA system present in S.
aureus nor another efflux pump system is the main reason for bacterial resistance
to QACs. Our findings suggest that membrane composition could be the predominant
driver that allows CA-MRSA to withstand the assault of conventional QAC
antiseptics.
PMID- 28510319
TI - Response to Zinicola et al.
PMID- 28510318
TI - Report From the American Society of Transplantation Conference on Donor Heart
Selection in Adult Cardiac Transplantation in the United States.
AB - Cardiac transplantation remains the only definitive treatment for end-stage heart
failure. Transplantation rates are limited by a shortage of donor hearts. This
shortage is magnified because many hearts are discarded because of strict
selection criteria and concern for regulatory reprimand for less-than-optimal
posttransplant outcomes. There is no standardized approach to donor selection
despite proposals to liberalize acceptance criteria. A donor heart selection
conference was organized to facilitate discussion and generate ideas for future
research. The event was attended by 66 participants from 41 centers with
considerable experience in cardiac donor selection. There were state-of-the-art
presentations on donor selection, with subsequent breakout sessions on
standardizing the process and increasing utilization of donor hearts.
Participants debated misconceptions and established agreement on donor and
recipient risk factors for donor selection and identified the components
necessary for a future donor risk score. Ideas for future initiatives include
modification of regulatory practices to consider extended criteria donors when
evaluating outcomes and prospective studies aimed at identifying the factors
leading to nonacceptance of available donor hearts. With agreement on the most
important donor and recipient risk factors, it is anticipated that a consistent
approach to donor selection will improve rates of heart transplantation.
PMID- 28510320
TI - Selective Si-C(sp3 ) Bond Cleavage in (Aminomethyl)silanes by Carbanionic
Nucleophiles and Its Stereochemical Course.
AB - Selective cleavage of a silicon-carbon bond in tetraorganosilanes is still a
great challenge. A new type of Si-C(sp3 ) bond cleavage in bench-stable
(aminomethyl)silanes with common organolithium reagents as nucleophiles has now
been identified. Suitable leaving groups are benzyl, allyl, and phenylthiomethyl
groups. A beta-donor function and polar solvents are essential for the reaction.
Simple switching between alpha-deprotonation and substitution is possible through
slight modifications of the reaction conditions. The stereochemical course of the
reaction was elucidated by using a silicon-chiral benzylsilane. The new
transformation proceeds stereospecifically with inversion of configuration and
can be used for the targeted synthesis of enantiomerically pure
tetraorganosilanes, which are otherwise difficult to access. Quantum chemical
calculations provided insight into the mechanism of the new substitution.
PMID- 28510321
TI - Novel ZnS/Carbon Nanofiber Photocatalyst for Degradation of Rhodamine 6G:
Kinetics Tracking of Operational Parameters and Development of a Kinetics Model.
AB - A novel nanocomposite in the role of photocatalyst was prepared by composition of
zinc sulfide (ZnS) nanoparticles with carbon nanofibers (CNFs) and was
characterized. The XRD, EDX, and FE-SEM analysis revealed that ZnS is
successfully embedded in CNFs matrix. The DRS results indicated that supporting
of ZnS by CNFs led to a decrease of the band gap energy. The photocatalytic
degradation of a hazardous xanthine dye, Rhodamine 6 G (Rh-6G), by the prepared
ZnS/CNFs composite was examined from the kinetics point of view. Nonlinear
regression analysis was used to develop a mathematical kinetics model based on
the Langmuir-Hinshelwood mechanism, and an empirical equation was obtained for
the estimation of apparent pseudo-first-order rate constant (kap ) as a function
of operational parameters (viz. initial dye concentration, ZnS/CNFs content, pH,
and irradiation intensity). Based on the results, kap increased with an increase
ZnS/CNFs content, pH, and UV light intensity, whereas it decreased by increasing
the initial Rh-6G concentration. Moreover, a new kinetics model was obtained
based on proposed elementary steps to determine kap . In the final stage of the
work, intermediate materials produced within photocatalytic degradation of Rh-6G
dye were detected by GC-MS analysis.
PMID- 28510322
TI - Does Medical Students Knowing More About Drugs Lead to Better Treatment Choices?
PMID- 28510324
TI - Mutual Gaze During Early Mother-Infant Interactions Promotes Attention Control
Development.
AB - Efficient attention control is fundamental for infant cognitive development, but
its early precursors are not well understood. This study investigated whether
dyadic visual attention during parent-infant interactions at 5 months of age
predicts the ability to control attention at 11 months of age (N = 55). Total
duration of mutual gaze (MG) was assessed during free play at 5 months, while
infant attention control was measured in a gap-and-overlap task at 5 and 11
months. MG predicted attention disengagement at 11 months. Infants who spent more
time in MG at 5 months showed better attention control at 11 months. These
results provide important insights into developmental pathways linking visual
behavior in dyadic interactions with infants' subsequent attention skills.
PMID- 28510323
TI - A Systematic Review and Pooled Analysis of Select Safety Parameters Among Normal
Healthy Volunteers Taking Placebo in Phase 1 Clinical Trials.
AB - A systematic review of the Bristol-Myers Squibb normal healthy volunteers (NHVs)
database identified phase 1 trials that included NHVs administered placebo with
the aim of characterizing normal inter- and intraindividual safety parameter
variability. Twenty-five single and multiple ascending dose studies, median
duration 28 (2 to 63) days, were included in the pooled analysis (355 NHVs).
Laboratory evaluations, vital signs, electrocardiograms, and adverse events were
assessed. The most commonly occurring adverse event was headache (28 [7.9%] NHVs;
519.5 events/100 person-years). During the dosing period (on placebo),
evaluations showed 5.1 events/100 measures of alanine aminotransferase and 7.3
events/100 measures of creatine kinase 1* above the upper limit of normal.
Alanine aminotransferase and creatine kinase elevations occurred in 28 (7.9%) and
39 (11.0%) NHVs, respectively; 105 (30.3%) NHVs had low and 46 (13.3%) had high
diastolic blood pressure. This analysis may inform future study designs and
provide a context for interpretation of safety signals in early phase clinical
trials.
PMID- 28510325
TI - Structural Dynamics upon Photoexcitation in a Spin Crossover Crystal Probed with
Femtosecond Electron Diffraction.
AB - Photoexcitation of spin crossover (SCO) complexes can trigger extensive
electronic spin transitions and transformation of molecular structure. However,
the precise nature of the associated ultrafast structural dynamics remains
elusive, especially in the solid state. Here, we studied a single-crystal SCO
material with femtosecond electron diffraction (FED). The unique capability of
FED allows us to directly probe atomic motions and to track ultrafast structural
changes within a crystal lattice. By monitoring the time-dependent changes of the
Bragg reflections, we observed the formation of a photoinduced structure similar
to the thermally induced high-spin state. The data and refinement calculations
indicate the global structural reorganization within 2.3 ps, as the metal-ligand
bond distribution narrows during intramolecular vibrational energy redistribution
(IVR) driving the intermolecular rearrangement. Three independent dynamical group
are identified to model the structural dynamics upon photoinduced SCO.
PMID- 28510326
TI - Total Synthesis of Homodimericin A.
AB - We report the concise total synthesis of homodimericin A (1), a recently
identified fungal metabolite bearing an unprecedented molecular architecture. The
success of the approach hinges on a series of rationally designed and bioinspired
transformations, including a Moore rearrangement to assemble the monomeric
hydroquinone precursor, homodimerization through double Michael addition to
construct the planar A/B/C tricyclic framework, and a tandem Diels-Alder
reaction/carbonyl-ene cyclization to forge the congested D/E/F tricyclic cage
motif. Unequivocal evidence for the elucidated structure of homodimericin A was
also provided by this study.
PMID- 28510327
TI - Pre-existing diabetes is a risk factor for increased rates of cellular rejection
after kidney transplantation: an observational cohort study.
AB - AIM: To investigate whether people with diabetes have an elevated risk of kidney
allograft rejection in a well characterized clinical cohort in the setting of
contemporary immunosuppression. METHODS: We conducted a retrospective cohort
study including all kidney allograft recipients at a single centre between 2007
and 2015, linking clinical, biochemical and histopathological data from
electronic patient records. RESULTS: Data were analysed for 1140 kidney
transplant recipients. The median follow-up was 4.4 years post-transplantation,
and 117 of the kidney transplant recipients (10.2%) had diabetes at time of
transplantation. Kidney allograft recipients with vs without diabetes were older
(53 vs 45 years; P<0.001) and more likely to be non-white (41.0% vs 26.4%;
P=0.001). Kidney allograft recipients with vs without diabetes had a higher risk
of cellular rejection (19.7% vs 12.4%; P=0.024), but not of antibody-mediated
rejection (3.4% vs 3.7%; P=0.564). Graft function and risk of death-censored
graft loss were similar in the two groups, but kidney allograft recipients with
diabetes had a higher risk of death and overall graft loss than those without
diabetes. In a Cox regression model of non-modifiable risk factors at time of
transplantation, diabetes was found to be an independent risk factor for cellular
rejection (hazard ratio 1.445, 95% CI 1.023-1.945; P=0.042). CONCLUSIONS: Kidney
allograft recipients with diabetes at transplantation should be counselled
regarding their increased risk of cellular rejection but reassured regarding the
lack of any adverse impact on short-to-medium term allograft function or
survival.
PMID- 28510329
TI - Isolation of Stem Cells and Progenitors from Mouse Epidermis.
AB - The epidermis consists of several distinct compartments including the
interfollicular epidermis (IFE), sweat glands, sebaceous glands (SGs), and the
hair follicle (HF). While the IFE and SGs are in a constant state of self
renewal, the HF cycles between phases of growth, destruction, and rest. The hair
follicle stem cells (HFSCs) that fuel this perpetual cycle have been well
described and are located in a niche termed the bulge. These bulge SCs express
markers such as CD34 and Keratin 15 (K15), enabling the isolation of these cells.
Here, we describe a powerful method for isolating HFSCs and epidermal progenitors
from mouse skin utilizing fluorescence activated cell-sorting (FACS). Upon
isolation, cells can be expanded and utilized in various in vivo and in vitro
models aimed at studying the function of these unique cells. (c) 2017 by John
Wiley & Sons, Inc.
PMID- 28510330
TI - Rhesus Macaque iPSC Generation and Maintenance.
AB - The rhesus macaque (Macaca mulatta) is physiologically and phylogenetically
similar to humans, and therefore represents an invaluable model for the pre
clinical assessment of the safety and feasibility of iPSC-derived cell therapies.
The use of an excisable polycistronic lentiviral STEMCCA vector to reprogram
rhesus fibroblasts or bone marrow stromal cells (BMSCs) into RhiPSCs is
described. After reprogramming, the pluripotency transgenes can be removed by
transient expression of Cre, leaving a residual genetic tag that may be useful
for identification of RhiPSC-derived tissues in vivo. Finally, the steps to
maintain pluripotency during passaging of RhiPSCs, required for successful
utilization of RhiPSCs, is described. (c) 2017 by John Wiley & Sons, Inc.
PMID- 28510331
TI - Isolation of Ready-to-Use Adipose-Derived Stem Cell (ASC) Pellet for Clinical
Applications and a Comparative Overview of Alternate Methods for ASC Isolation.
AB - Current literature does not offer a standardized method to isolate adipose
derived stem cells (ASCs) for clinical applications and hence clinical studies
using ASCs often show inconsistent results. Most of these studies borrow
laboratory or benchside-derived protocols, which are complex, time consuming, and
involve the use of chemical, animal-derived reagents. In this unit we describe a
relatively simple and faster isolation protocol that allows collection of a ready
to-use ASC pellet for clinical application. All steps are performed in a closed
circuit in order to guarantee maximum process sterility. Once the adipose tissue
is harvested by means of a standard liposuction procedure, it undergoes a first
centrifugation in order to remove the oil and serous fractions. Then ASCs are
released by enzymatic digestion from the surrounding connective tissue scaffold.
Finally a double series of washing and centrifugation allows one to obtain the
ASC pellet alone. We usually graft this ASC pellet onto the skin edge and to the
bottom of chronic skin ulcers as ASCs proved to be effective in promoting wound
healing processes. Moreover, an increasing number of clinical studies are
currently ongoing to test their potential in every medical field, from
orthopedics to cardiology, oncology, autoimmune diseases, and tissue engineering.
(c) 2017 by John Wiley & Sons, Inc.
PMID- 28510328
TI - Genetic variants in the genes encoding rho GTPases and related regulators predict
cutaneous melanoma-specific survival.
AB - Rho GTPases control cell division, motility, adhesion, vesicular trafficking and
phagocytosis, which may affect progression and/or prognosis of cancers. Here, we
investigated associations between genetic variants of Rho GTPases-related genes
and cutaneous melanoma-specific survival (CMSS) by re-analyzing a published
melanoma genome-wide association study (GWAS) and validating the results in
another melanoma GWAS. In the single-locus analysis of 36,018 SNPs in 129 Rho
related genes, 427 SNPs were significantly associated with CMSS (p < 0.050 and
false-positive report probability <0.2) in the discovery dataset, and five SNPs
were replicated in the validation dataset. Among these, four SNPs (i.e., RHOU
rs10916352 G > C, ARHGAP22 rs3851552 T > C, ARHGAP44 rs72635537 C > T and
ARHGEF10 rs7826362 A > T) were independently predictive of CMSS (a meta-analysis
derived p = 9.04 * 10-4 , 9.58 * 10-4 , 1.21 * 10-4 and 8.47 * 10-4 ,
respectively). Additionally, patients with an increasing number of unfavorable
genotypes (NUGs) of these loci had markedly reduced CMSS in both discovery
dataset and validation dataset (ptrend =1.47 * 10-7 and 3.12 * 10-5 ). The model
including the NUGs and clinical variables demonstrated a significant improvement
in predicting the five-year CMSS. Moreover, rs10916352C and rs3851552C alleles
were significantly associated with an increased mRNA expression levels of RHOU (p
= 1.8 * 10-6 ) and ARHGAP22 (p = 5.0 * 10-6 ), respectively. These results may
provide promising prognostic biomarkers for CM personalized management and
treatment.
PMID- 28510332
TI - Human Umbilical Cord Mesenchymal Stromal Cell Isolation, Expansion,
Cryopreservation, and Characterization.
AB - Revised methods to derive, expand, and characterize mesenchymal stromal cells
(MSCs) from the umbilical cord are provided. Several considerations are taken for
GMP compliance including using a closed system isolation method and eliminating
several xenogenic components. With this method cells are isolated using
mechanical and enzymatic digestion and then expanded with high viabilities that
retain >90% viability after cryopreservation. Lastly, characterization methods
have been optimized to identify these cells as MSCs according to the ISCT minimal
criteria. This method standardizes the process for isolating, expanding,
cryopreserving, and characterizing MSCs from the umbilical cord. (c) 2017 by John
Wiley & Sons, Inc.
PMID- 28510334
TI - Angiogenesis within Stem Cell-Seeded Silk Scaffolds Cultured on the
Chorioallantoic Membrane and Visualized by 3D Imaging.
AB - The long-term survival and successful integration of implants for tissue
replacement and regeneration highly depends upon the fast ingrowth of blood
vessels from the surrounding tissues. Before selecting potential biomaterials for
clinical applications, they must be thoroughly tested with proper analytical
tools. This unit provides a protocol for studying the potential of cell-seeded
scaffolds to attract vessels that will form vascular networks within
biomaterials. It includes seeding of stem cells into silk fibroin scaffolds,
angiogenesis assay on the chorioallantoic membrane (CAM) of fertilized chicken
eggs, a procedure for perfusion with MicroFil, and finally microcomputed
tomography (uCT) scanning. This technique can help screen potential biomaterial
implants, thereby reducing the amount of animals needed for pre-clinical in vivo
studies. (c) 2017 by John Wiley & Sons, Inc.
PMID- 28510333
TI - Tetracycline-Inducible and Reversible Stable Gene Expression in Human iPSC
Derived Neural Progenitors and in the Postnatal Mouse Brain.
AB - The pB-tet-GOI plasmid system allows for stable piggyBac transposition-mediated
integration into cells, a fluorescent nuclear reporter to identify cells that
have been transfected, and robust transgene activation or suppression upon the
addition of dox to the cell culture or diet of the animal. Furthermore, the
addition of luciferase downstream of the target gene allows for quantitative
assessment of gene activity in a non-invasive manner. The protocols herein
provide instructions for the use of this system in cell lines and in the neonatal
mouse brain. Specifically, a detailed protocol is provided to illustrate: (1)
cloning of the respective GOI (genetic element(s) of interest); (2) nucleofection
of the plasmid system into human induced pluripotent stem cell (iPSC)-derived
neural progenitors; (3) dox-induced activation in vitro or in vivo; and (4) non
invasive assessment of gene activity in vivo by bioluminescence imaging. (c) 2017
by John Wiley & Sons, Inc.
PMID- 28510337
TI - Highly Rechargeable Lithium-CO2 Batteries with a Boron- and Nitrogen-Codoped
Holey-Graphene Cathode.
AB - Metal-air batteries, especially Li-air batteries, have attracted significant
research attention in the past decade. However, the electrochemical reactions
between CO2 (0.04 % in ambient air) with Li anode may lead to the irreversible
formation of insulating Li2 CO3 , making the battery less rechargeable. To make
the Li-CO2 batteries usable under ambient conditions, it is critical to develop
highly efficient catalysts for the CO2 reduction and evolution reactions and
investigate the electrochemical behavior of Li-CO2 batteries. Here, we
demonstrate a rechargeable Li-CO2 battery with a high reversibility by using B,N
codoped holey graphene as a highly efficient catalyst for CO2 reduction and
evolution reactions. Benefiting from the unique porous holey nanostructure and
high catalytic activity of the cathode, the as-prepared Li-CO2 batteries exhibit
high reversibility, low polarization, excellent rate performance, and superior
long-term cycling stability over 200 cycles at a high current density of 1.0 A g
1 . Our results open up new possibilities for the development of long-term Li-air
batteries reusable under ambient conditions, and the utilization and storage of
CO2 .
PMID- 28510335
TI - Proteoforms in Peripheral Blood Mononuclear Cells as Novel Rejection Biomarkers
in Liver Transplant Recipients.
AB - Biomarker profiles of acute rejection in liver transplant recipients could
enhance the diagnosis and management of recipients. Our aim was to identify
diagnostic proteoform signatures of acute rejection in circulating immune cells,
using an emergent "top-down" proteomics methodology. We prepared differentially
processed and cryopreserved cell lysates from 26 nonviral liver transplant
recipients by molecular weight-based fractionation and analyzed them by mass
spectrometry of whole proteins in three steps: (i) Nanocapillary liquid
chromatography coupled with high-resolution tandem mass spectrometry; (ii)
database searching to identify and characterize intact proteoforms; (iii) data
processing through a hierarchical linear model matching the study design to
quantify proteoform fold changes in patients with rejection versus normal liver
function versus acute dysfunction without rejection. Differentially expressed
proteoforms were seen in patients with rejection versus normal and nonspecific
controls, most evidently in the cell preparations stored in traditional serum
rich media. Mapping analysis of these proteins back to genes through gene
ontology and pathway analysis tools revealed multiple signaling pathways,
including inflammation mediated by cytokines and chemokines. Larger studies are
needed to validate these novel rejection signatures and test their predictive
value for use in clinical management.
PMID- 28510336
TI - Epistaxis in anticoagulated patients: Fewer hospital admissions and shorter
hospital stays on rivaroxaban compared to phenprocoumon.
AB - OBJECTIVES: Treatment of epistaxis in patients on anticoagulants is challenging
and associated with higher admission rates and longer hospital stays compared
with patients without anticoagulation. However, there is little information about
epistaxis in patients taking new direct oral anticoagulants such as rivaroxaban
compared with patients on traditional vitamin K antagonists such as
phenprocoumon. DESIGN: Retrospective cohort study. SETTING: The study was
conducted at the emergency department of the University Hospital Inselspital,
Bern, Switzerland. PARTICIPANTS: All admissions to the emergency department of
the University Hospital Inselspital, Bern, Switzerland from 1st July 2012 to 30th
June 2016 with non-traumatic epistaxis on anticoagulant therapy with
phenprocoumon or rivaroxaban were included. MAIN OUTCOME MEASURES: We compared
clinical outcome parameters (admission rates, length of hospital stay and
mortality) for both anticoagulant groups. RESULTS: We included 440 patients with
epistaxis, 123 (28%) on rivaroxaban and 317 (72%) on phenprocoumon. Fewer
hospital admissions and shorter hospital stays were found in patients under
rivaroxaban (12 (10.4%) vs 57 (18.0%) patients, P=.033; 0.7+/-2.2 vs 1.5+/-3.7
days, P=.011) compared with phenprocoumon. Anterior epistaxis was more common in
the rivaroxaban group in contrast to posterior epistaxis in patients on
phenprocoumon (74 (60.2%) vs 139 (43.8%) patients, P=.002; 7 (5.7%) vs 39 (12.3%)
patients, P=.042). CONCLUSIONS: Our data suggests that epistaxis on direct oral
anticoagulation with rivaroxaban is associated with shorter hospital stays and
fewer hospital admissions than epistaxis on vitamin K antagonist phenprocoumon.
PMID- 28510338
TI - Therapeutic Targeting of Poly(ADP-Ribose) Polymerase-1 (PARP1) in Cancer: Current
Developments, Therapeutic Strategies, and Future Opportunities.
AB - Poly(ADP-ribose) polymerase-1 (PARP-1) plays a central role in numerous cellular
processes including DNA repair, replication, and transcription. PARP interacts
directly, indirectly or via PARylation with various oncogenic proteins and
regulates several transcription factors thereby modulating carcinogenesis.
Therapeutic inhibition of PARP is therefore perceived as a promising anticancer
strategy and a number of PARP inhibitors (PARPi) are currently under development
and clinical evaluation. PARPi inhibit the DNA repair pathway and thus form the
concept of synthetic lethality in cancer therapeutics. Preclinical and clinical
studies have shown the potential of PARPi as chemopotentiator, radiosensitizer,
or as adjuvant therapeutic agents. Recent studies have shown that PARP-1 could be
either oncogenic or tumor suppressive in different cancers. PARP inhibitor
resistance is also a growing concern in the clinical setting. Recently, changes
in the levels of PARP-1 activity or expression in cancer patients have provided
the basis for consideration of PARP-1 regulatory proteins as potential
biomarkers. This review focuses on the current developments related to the role
of PARP in cancer progression, therapeutic strategies targeting PARP-associated
oncogenic signaling, and future opportunities in use of PARPi in anticancer
therapeutics.
PMID- 28510339
TI - Pharmacokinetics of Tedizolid in Obese and Nonobese Subjects.
PMID- 28510340
TI - Immortal time bias or sorafenib effect in elderly patients with HCC?
PMID- 28510341
TI - Living Donor Liver Transplantation for Patients Older Than Age 70 Years: A Single
Center Experience.
AB - Over the past two decades, the age of liver transplantation (LT) recipients has
been increasing. We reviewed our experience with LT for patients aged >=70 years
(range: 70-78 years) and investigated the feasibility of performing LT,
especially living donor LT (LDLT), for older patients. We retrospectively
reviewed the medical records of 25 patients (15 LDLT recipients, 10 deceased
donor LT recipients) aged >=70 years who underwent LT from January 2000 to April
2016. Their perioperative morbidity rate was 28.0%, and the in-hospital mortality
rate was 16.0%; these results were comparable to those of matched patients in
their 60s (n = 73; morbidity, p = 0.726; mortality, p = 0.816). For patients in
their 70s, the 1- and 5-year patient survival rates were 84.0% and 69.8%, and the
1- and 5-year graft survival rates were 83.5% and 75.1%, respectively.
Comparisons of patient and graft survival rates between matched patients in their
60s and 70s showed no statistically significant differences (patient survival, p
= 0.372; graft survival, p = 0.183). Our experience suggests that patients aged
>=70 years should not be excluded from LT, or even LDLT, based solely on age and
implies that careful selection of recipients and donors as well as meticulous
surgical technique are necessary for successful results.
PMID- 28510342
TI - Constructing a Robust Fluorescent DNA-Stabilized Silver Nanocluster Probe Module
by Attaching a Duplex Moiety.
AB - Fluorescent DNA-templated silver nanoclusters (DNA-Ag NCs) have served as
excellent luminescent probes and operation units in various applications.
However, the fluorescence property of DNA-Ag NCs is very sensitive to elongation
or modification of the DNA template, limiting the breadth of applications. In
this work, we propose a strategy for constructing a robust fluorescent DNA-Ag NCs
probe module by attaching a duplex moiety to the nanocluster-bearing sequence.
The fluorescence intensity of the DNA-Ag NCs can be enhanced 90-fold upon
hybridization of the elongated moiety. Adenine in the linker sequence has a
further enhancing effect on the fluorescence intensity, whereas thymine has a
quenching effect. The transformation from a non-fluorescent species to
fluorescent nanoclusters is responsible for the fluorescence enhancement with
duplex formation of the elongated moiety. We hope that this design will aid
future diversification of experimental designs to facilitate more applications
that are currently limited by the aforementioned problems.
PMID- 28510344
TI - Harnessing [1,4], [1,5], and [1,6] Anionic Fries-type Rearrangements by Reaction
Time Control in Flow.
AB - A series of anionic Fries-type rearrangements of carbamoyl-substituted
aryllithium intermediates were controlled by using flow microreactor systems. For
the [1,4] and [1,5] rearrangements, the aryllithium intermediate formed before
carbamoyl migration and the lithium alkoxide formed after carbamoyl migration can
be selectively subjected to subsequent reactions with electrophiles by precisely
controlling the residence time and temperature (-25 to -50 degrees C). In
contrast, the [1,6] rearrangement is rather slow even at -25 degrees C. The
absence of crossover products indicates the intramolecular nature of the
carbamoyl group migration.
PMID- 28510343
TI - No effect of HLA-C mismatch after allogeneic hematopoietic stem cell
transplantation with unrelated donors and T-cell depletion in patients with
hematological malignancies.
AB - HLA-C mismatch in unrelated donor's hematopoietic stem cell transplantation
(HSCT) has been associated with poor patient outcome. However, the impact of HLA
C mismatch in the context of HSCT combined with in vivo T-cell depletion remains
unclear. We therefore performed a single-center, retrospective analysis of the
clinical outcome on patients with hematological malignancies treated with allo
HSCT, who underwent T-cell depletion. The majority of the patients (n=276)
received a HLA-A, HLA-B, HLA-DRB1-matched graft that were either also HLA-C
matched (n=260), or patients with the permissive HLA-C*03:03/03:04 mismatch
(n=16), while the remaining patients (n=95) received a HLA-C-mismatched graft
(excluding HLA-C*03:03/03:04 mismatches). We did not observe any significant
differences between the HLA-C-matched patients (including the permissive HLA
C*03:03/03:04 mismatch) and the HLA-C-mismatched patients regarding cumulative
proportion surviving, graft failure, relapse-free survival, relapse, or acute
graft-versus-host disease. Our data suggest that in the context of high dose T
lymphocyte-depleting agents, HLA-C matching is not essential for patients with
hematological malignancies.
PMID- 28510345
TI - Mandarin parents' evaluation of developmental status in the detection of delays.
AB - BACKGROUND: We examined the parental perception and accuracy of the Mandarin
translation of the Parents' Evaluation of Developmental Status, a screening
questionnaire for parent concerns about children's various developmental skills.
METHODS: The questionnaire was translated into Mandarin. Upon enrollment,
caregivers completed the Mandarin PEDS and answered four questions about its
acceptability and usefulness, and its ease of understanding and completion. The
Mandarin PEDS was independently evaluated by a pediatrician and a community
nurse, and classified as high risk (>=two predictive concerns), medium risk (one
predictive concern), low risk (any non-predictive concerns) or no risk (if no
concern) for developmental delays. The caregivers repeated Mandarin PEDS at a 2
week interval for test-retest reliability, while the children underwent testing
for accuracy using a developmental assessment test. RESULTS: The majority (>=85%)
of the 73 caregivers perceived the Mandarin PEDS as acceptable and useful, as
well as easy to understand and complete. Fifteen (20.5%) and 24 responses (33.9%)
were classified as high and moderate risk, respectively. The test-retest and
inter-rater reliabilities were excellent, with an intra-class correlation
coefficient of 0.812 (95% CI: 0.701-0.881, P < 0.001) and a kappa value of 0.870
(P < 0.001), respectively. Mandarin PEDS was 80.0% sensitive and 83.8% specific
for those in the high-risk category (adjusted OR, 64.68; 95% CI: 1.33-3,139.72; P
= 0.035). CONCLUSION: Mandarin PEDS was well received by the caregivers, and was
reliable and accurate in detecting developmental delays in the Mandarin-speaking
subjects. We recommend it for early detection of children with developmental and
behavioral problems.
PMID- 28510346
TI - Lack of Effect of Rivipansel on QTc Interval in Healthy Adult African American
Male Subjects.
AB - Rivipansel is a pan-selectin inhibitor in phase 3 development for the treatment
of vaso-occlusive crises in patients with sickle cell disease. This single-dose,
randomized, 3-period, 3-treatment (400 mg moxifloxacin open-label, 4 g rivipansel
blinded, and placebo-blinded) crossover study evaluated the effect of rivipansel
on the QT/QTc interval in 48 healthy male African American subjects (age, 21-53
years; weight, 60-115 kg). Time-matched, placebo-adjusted change from baseline QT
interval using Fridericia's correction method (QTcF) was determined using a
repeated-measures mixed-effects model. The highest upper bound of the 2-sided 90%
confidence interval (CI) for QTcF change was 3.22 milliseconds 3 hours postdose.
Moxifloxacin showed the anticipated QTcF effect, indicating that the study had
adequate sensitivity to detect changes in the QTcF interval. The study concluded
that no QTcF effect was demonstrated with rivipansel compared with placebo, as
the upper bound of the 2-sided 90%CI was less than 10 milliseconds at all times.
Exposure-response modeling for rivipansel concentrations and change from baseline
in QTcF data corroborated a lack of effect with rivipansel compared with placebo.
Single doses of rivipansel 4 g by intravenous infusion over 20 minutes were well
tolerated in this study.
PMID- 28510348
TI - Regioselective Synthesis of Polycyclic and Heptagon-embedded Aromatic Compounds
through a Versatile pi-Extension of Aryl Halides.
AB - A versatile pi-extension reaction was developed based on the three-component
cross-coupling of aryl halides, 2-haloarylcarboxylic acids, and norbornadiene.
The transformation is driven by the direction and subsequent decarboxylation of
the carboxyl group, while norbornadiene serves as an ortho-C-H activator and
ethylene synthon via a retro-Diels-Alder reaction. Comprehensive DFT calculations
were performed to account for the catalytic intermediates.
PMID- 28510347
TI - Bioluminescent Antibodies for Point-of-Care Diagnostics.
AB - We introduce a general method to transform antibodies into ratiometric,
bioluminescent sensor proteins for the no-wash quantification of analytes. Our
approach is based on the genetic fusion of antibody fragments to NanoLuc
luciferase and SNAP-tag, the latter being labeled with a synthetic fluorescent
competitor of the antigen. Binding of the antigen, here synthetic drugs, by the
sensor displaces the tethered fluorescent competitor from the antibody and
disrupts bioluminescent resonance energy transfer (BRET) between the luciferase
and fluorophore. The semisynthetic sensors display a tunable response range
(submicromolar to submillimolar) and large dynamic range (DeltaRmax >500 %), and
they permit the quantification of analytes through spotting of the samples onto
paper followed by analysis with a digital camera.
PMID- 28510349
TI - Potential Disadvantages of Overcentralization of Organ Recovery Centers: Response
to Marsolais et al.
PMID- 28510352
TI - Spotlights on our sister journals: Angew. Chem. Int. Ed. 22/2017.
PMID- 28510350
TI - Real-life comparison of three general paediatric wards showed similar outcomes
for children with bronchiolitis despite different treatment regimens.
AB - AIM: This study evaluated the effectiveness of three different treatments for
bronchiolitis in a tertiary paediatric facility. METHODS: Patients with
bronchiolitis who were younger than two years of age and were randomly allocated
to three general wards at Schneider Children's Medical Center, Israel, after
admission were included. Different treatment protocols in the wards were
retrospectively compared. RESULTS: The study comprised 286 children. The clinical
and laboratory parameters on admission were similar between the wards. In Ward C
where nebulised hypertonic saline was infrequently administered (6.7%), the mean
number of days with oxygen saturation under 92% and the meanlength of hospital
stay (1.8 and 3.8 days) were significantly lower than Ward A (2.8 and 5.3 days)
and Ward B, (2.9 and 4.7 days) where nebulised hypertonic saline was given more
frequently (38.7%-74.7%). Multivariate analysis indicated that low saturation on
admission, leukocytosis and use of nebulised hypertonic saline or adrenalin were
independent predictors of a longer period of desaturation and hospital stay.
CONCLUSION: Different treatment protocols for bronchiolitis were used in three
paediatric wards in this real-life study. No treatment regimen proved superior.
Inhalations of hypertonic saline or adrenaline were associated with a longer
hospital stay.
PMID- 28510351
TI - Using N-Heterocyclic Vinyl Ligands to Access Stable Divinylgermylenes and a
Germylium Cation.
AB - Two efficient methods are presented to install sigma- and pi-electron-donating N
heterocyclic vinyl groups onto main-group elements (E): halosilane elimination
and base-induced E-C bond formation. Placement of two NHC=CH- ligands (NHC=N
heterocyclic carbene) onto a GeII center affords a two-coordinate germylene, a
heavy congener of the elusive divinyl carbenes. The pi-donating ability of this
vinylic ligand scaffold was further demonstrated by the synthesis of a three
coordinate germylium cation R3 Ge+ .
PMID- 28510353
TI - Crystal-Packing-Driven Enrichment of Atropoisomers.
AB - Crystal-packing forces can have a significant impact on the relative stabilities
of different molecules and their conformations. The magnitude of such effects is,
however, not yet well understood. Herein we show, that crystal packing can
completely overrule the relative stabilities of different stereoisomers in
solution. Heating of atropoisomers (i.e. "frozen-out" conformational isomers) in
solution leads to complex mixtures. In contrast, solid-state heating selectively
amplifies minor (<25 mole %) components of these solution-phase mixtures. We show
that this heating strategy is successful for compounds with up to four
rotationally hindered sigma bonds, for which a single stereoisomer out of seven
can be amplified selectively. Our results demonstrate that common supramolecular
interactions-for example, [methyl???pi] coordination and [C-H???O] hydrogen
bonding-can readily invert the relative thermodynamic stabilities of different
molecular conformations. These findings open up potential new avenues to control
the folding of macromolecules.
PMID- 28510354
TI - That's what friends are for: how intergroup friendships promote historically
disadvantaged groups' substantive political representation.
AB - The interests of historically disadvantaged groups risk being overlooked if they
are not present in the decision-making process. However, a mere presence in
politics does not guarantee political success. Often groups need allies to
promote their interests successfully. We argue that one way to identify such
allies is to judge politicians by whether they have friends in historically
disadvantaged groups, as intergroup friendships have been shown to make people
understand and feel empathy for outgroups. In other words, intergroup friendships
may function as an important complement to descriptive representation. We test
our argument with a unique survey that asks all elected political representatives
in Sweden's 290 municipalities (response rate 79 per cent) about their friendship
ties to, and their representation of, five historically disadvantaged groups:
women, immigrants, youths, pensioners and blue-collar workers. We find a strong
correlation between representatives' friendship ties to these groups and their
commitment to represent them. The correlation is especially strong for youths and
blue-collar workers, which likely can be explained by the fact that these groups
usually lack crucial political resources (such as experience and education). We
conclude that friendship ties function as an important complement to descriptive
representation for achieving substantive representation.
PMID- 28510356
TI - Purification of recombinant Abeta(1-42) and pGlu-Abeta(3-42) using preparative
SDS-PAGE.
AB - Recombinant expression and purification of amyloid peptides represents a common
basis for investigating the molecular mechanisms of amyloid formation and
toxicity. However, the isolation of the recombinant peptides is hampered by
inefficient separation from contaminants such as the fusion protein required for
efficient expression in E. coli. Here, we present a new approach for the
isolation of highly purified Abeta(1-42) and pGlu-Abeta(3-42), which is based on
a separation using preparative SDS-PAGE. The method relies on the purification of
the Abeta fusion protein by affinity chromatography followed by preparative SDS
PAGE under reducing conditions and subsequent removal of detergents by
precipitation. The application of preparative SDS-PAGE represents the key step to
isolate highly pure recombinant Abeta, which has been applied for
characterization of aggregation and toxicity. Thereby, the yield of the
purification strategy was >60%. To the best of our knowledge, this is the first
description of an electrophoresis-based method for purification of a recombinant
Abeta peptide. Therefore, the method might be of interest for isolation of other
amyloid peptides, which are critical for conventional purification strategies due
to their aggregation propensity.
PMID- 28510355
TI - The National Landscape of Living Kidney Donor Follow-Up in the United States.
AB - In 2013, the Organ Procurement and Transplantation Network (OPTN)/ United Network
for Organ Sharing (UNOS) mandated that transplant centers collect data on living
kidney donors (LKDs) at 6 months, 1 year, and 2 years postdonation, with policy
defined thresholds for the proportion of complete living donor follow-up (LDF)
data submitted in a timely manner (60 days before or after the expected visit
date). While mandated, it was unclear how centers across the country would
perform in meeting thresholds, given potential donor and center-level challenges
of LDF. To better understand the impact of this policy, we studied Scientific
Registry of Transplant Recipients data for 31,615 LKDs between January 2010 and
June 2015, comparing proportions of complete and timely LDF form submissions
before and after policy implementation. We also used multilevel logistic
regression to assess donor- and center-level characteristics associated with
complete and timely LDF submissions. Complete and timely 2-year LDF increased
from 33% prepolicy (January 2010 through January 2013) to 54% postpolicy
(February 2013 through June 2015) (p < 0.001). In an adjusted model, the odds of
2-year LDF increased by 22% per year prepolicy (p < 0.001) and 23% per year
postpolicy (p < 0.001). Despite these annual increases in LDF, only 43% (87/202)
of centers met the OPTN/UNOS-required 6-month, 1-year, and 2-year LDF thresholds
for LKDs who donated in 2013. These findings motivate further evaluation of LDF
barriers and the optimal approaches to capturing outcomes after living donation.
PMID- 28510357
TI - KIF11 silencing and inhibition induces chromosome instability that may contribute
to cancer.
AB - Understanding the aberrant pathways that contribute to oncogenesis and
identifying the altered genes involved in these pathways is a critical first step
to develop effective strategies to better combat cancer. Chromosome instability
(CIN) is an aberrant phenotype that occurs in ~80% of all cancer types and is
associated with aggressive tumors, the acquisition of multidrug resistance and
poor patient prognosis. Despite these associations however, the aberrant genes
and molecular defects underlying CIN remain poorly understood. KIF11 is an
evolutionarily conserved microtubule motor protein that functions in centrosome
and chromosome dynamics in mitosis. Interestingly, the yeast ortholog of KIF11,
namely CIN8 is a CIN gene and thus aberrant KIF11 expression and function is
suspected to underlie CIN. In support of this possibility, KIF11 is somatically
altered in a large number of cancer types. Using a complementary biochemical and
genetic approach we examined whether KIF11 silencing with siRNAs or inhibition
with monastrol was able to convert two distinct and karyotypically stable cell
lines into karyotypically unstable cell lines. Indeed, quantitative imaging
microscopy and flow cytometry revealed that KIF11 silencing induced increases in
nuclear areas, micronucleus formation, DNA content and chromosome numbers
relative to controls that was also observed following KIF11 inhibition.
Collectively, this study identifies and validates KIF11 as an evolutionarily
conserved CIN gene, and further suggests that aberrant expression and function
may contribute to the pathogenesis of a subset of cancers.
PMID- 28510358
TI - Bottom-Up Design of a Copper-Ruthenium Nanoparticulate Catalyst for Low
Temperature Ammonia Oxidation.
AB - A novel nanoparticulate catalyst of copper (Cu) and ruthenium (Ru) was designed
for low-temperature ammonia oxidation at near-stoichiometric mixtures using a
bottom-up approach. A synergistic effect of the two metals was found. An optimum
CuRu catalyst presents a reaction rate threefold higher than that for Ru and
forty-fold higher than that for Cu. X-ray absorption spectroscopy suggests that
in the most active catalyst Cu forms one or two monolayer thick patches on Ru and
the catalysts are less active once 3D Cu islands form. The good performance of
the tuned Cu/Ru catalyst is attributed to changes in the electronic structure,
and thus the altered adsorption properties of the surface Cu sites.
PMID- 28510360
TI - Analysis of Human Papillomavirus Genome Replication Using Two- and Three
Dimensional Agarose Gel Electrophoresis.
AB - This unit includes the necessary information to conduct neutral/neutral and
neutral/alkaline two-dimensional and neutral/neutral/alkaline three-dimensional
agarose gel electrophoresis. The methodology has been optimized over the years to
gain a better outcome from the hard-to-interpret signals of human papilloma virus
replication intermediates obtained from two- and three-dimensional agarose gels.
Examples of typical results and interpretation of replication intermediate
patterns are included, and the outcomes of multiple-dimension assays are assessed
using previously published experimental data. (c) 2017 by John Wiley & Sons, Inc.
PMID- 28510359
TI - Isolation, Culture and Cryopreservation of Sarcocystis species.
AB - More than 200 valid Sarcocystis species have been described in the
parasitological literature. The developmental life cycle in the intermediate host
and definitive host has only been described for a few species. Sarcocystis
parasites are common pathogens infecting a wide range of animals, including
humans, and this unit reviews the methods used for isolating infective stages of
the parasite from both definitive and intermediate host(s), as well as methods
used to initiate cultures from sporocysts and merozoites and for cryopreservation
of various Sarcocystis spp. These methods are based on published reports and our
experience with Sarcocystis species in cell culture over many years. The
information presented is suitable for the efficient culture of many Sarcocystis
species; however, some minor modifications may be needed based on the unique
developmental patterns of some species. (c) 2017 by John Wiley & Sons, Inc.
PMID- 28510361
TI - Chlamydia trachomatis Transformation and Allelic Exchange Mutagenesis.
AB - Gene inactivation is essential for forward and reverse genetic approaches to
establish protein function. Techniques such as insertion or chemical mutagenesis
have been developed to mutagenize chlamydiae via targeted or random mutagenesis,
respectively. Both of these approaches require transformation of chlamydiae to
either introduce insertion elements or complement mutants. We have recently
developed a targeted mutagenesis strategy, fluorescence-reported allelic exchange
mutagenesis (FRAEM), to delete Chlamydia trachomatis L2 genes. This approach
overcomes several barriers for genetically manipulating intracellular bacteria.
Perhaps most significantly, FRAEM employs fluorescence reporting to indicate
successful transformation and subsequent recombination events. Three protocols
are provided that detail methods to construct gene-specific suicide vectors,
transform C. trachomatis L2 to select for recombinants, and isolate clonal
populations via limiting dilution. In aggregate, these protocols will allow
investigators to engineer C. trachomatis L2 strains carrying complete deletions
of desired gene(s). (c) 2017 by John Wiley & Sons, Inc.
PMID- 28510362
TI - Burkholderia thailandensis: Genetic Manipulation.
AB - Burkholderia thailandensis is a Gram-negative bacterium endemic to Southeast
Asian and northern Australian soils. It is non-pathogenic; therefore, it is
commonly used as a model organism for the related human pathogens Burkholderia
mallei and Burkholderia pseudomallei. B. thailandensis is relatively easily
genetically manipulated and a variety of robust genetic tools can be used in this
organism. This unit describes protocols for conjugation, natural transformation,
mini-Tn7 insertion, and allelic exchange in B. thailandensis. (c) 2017 by John
Wiley & Sons, Inc.
PMID- 28510364
TI - Lyophilization of Bdellovibrio bacteriovorus 109J for Long-Term Storage.
AB - Bdellovibrio bacteriovorus 109J is a Gram-negative predatory bacterium with
obligate host dependency on other Gram-negative bacteria. This bacteriolytic
predator collides with, enters, and establishes growth within the prey (host)
periplasm, eventually lysing the prey cell wall to release fresh, motile B.
bacteriovorus progeny. Laboratory maintenance of B. bacteriovorus has been
previously described by other investigators. The protocols included in this unit
deal with the technique required to lyophilize or freeze dry host-dependent B.
bacteriovorus. This is an alternative means to frozen glycerol stocks for the
long-term storage of B. bacteriovorus. It includes the cultivation process and
methods to lyophilize B. bacteriovorus as well as recommended storage conditions.
In addition, this unit provides insight on the formulation's shelf-life including
the time to active culture after reviving lyophilized stocks of B. bacteriovorus
following short-, medium-, and long-term storage. (c) 2017 by John Wiley & Sons,
Inc.
PMID- 28510365
TI - Construction of the Benzomesembrine Skeleton: Palladium(0)-Catalyzed
Intermolecular Arylative Dearomatization of alpha-Naphthols and Subsequent Aza
Michael Reaction.
AB - A novel palladium(0)-catalyzed intermolecular arylative dearomatization of alpha
naphthols and subsequent aza-Michael reaction is described. Two adjacent
stereocenters were constructed efficiently through consecutive arylative
dearomatization and Michael addition reactions. By utilizing this method,
structurally diverse benzomesembrine derivatives were synthesized with excellent
yields and chemoselectivity. The benzomesembrine products were shown to undergo
versatile functional-group transformations.
PMID- 28510363
TI - Purification Toxoplasma gondii Tissue Cysts Using Percoll Gradients.
AB - The protozoan parasite Toxoplasma gondii is capable of infecting all warm-blooded
animals and humans. Infectious, transmissible forms of the parasite include
oocysts produced by the sexual cycle within the definitive feline host and tissue
cysts that form Toxoplasma in the central nervous system and muscle during the
asexual cycle within all chronically infected warm-blooded hosts. These tissue
cysts are populated with slow-growing bradyzoites, which until recently have been
thought to be dormant entities in the context of immune sufficiency. Reactivation
to active growth during immune suppression is of critical clinical importance.
However, little is known about tissue cysts or the bradyzoites they house, as the
diversity of tissue cysts cannot be replicated in cell culture systems. This
protocol for optimization of tissue cyst purification from the brains of infected
mice using Percoll gradients provides an efficient means to recover in vivo
derived tissue cysts that can be applied to imaging, cell biological,
biochemical, transcriptomic, and proteomic analyses. (c) 2017 by John Wiley &
Sons, Inc.
PMID- 28510367
TI - Reply.
PMID- 28510366
TI - HMGA2 plays an important role in Cr (VI)-induced autophagy.
AB - Cr (VI) is mutagenic and carcinogenic, but the mechanism is unclear. In this
study, the involvement of high mobility group A2 (HMGA2) in Cr (VI)-induced
autophagy was investigated. Cr (VI) treatment induced formation of
autophagosomes, increased expression of LC3II, Atg12-Atg5, Atg4, Atg10, HMGA1 and
HMGA2 proteins, and decreased the expression of p62 in A549 cells. Silencing of
HMGA2 gene by siRNA blocked Cr (VI)-induced formation of autophagosomes,
expression of LC3II, Atg12-Atg5, Atg10 and reduction of p62. Overexpression of
HMGA2 in HEK 293 and HeLa cells could induce the expression of LC3II, Atg12-Atg5
and Atg10, and decrease the expression of p62. Although the protein level of
Atg12-Atg5 conjugation changed after Cr (VI) treatment, silencing of HMGA2 and
overexpression of HMGA2, both the proteins and mRNA levels of Atg12 and Atg5 were
not changed significantly. ChIP assay demonstrated that HMGA2 protein directly
bound to the promoter sequence of Atg10 gene, which modulated the conjugation of
Atg12-Atg5. Interestingly, 3-MA markedly prevented Cr (VI)-induced cell growth of
A549 cells. Our further in vivo study confirmed that the expression of HMGA1,
HMGA2, LC3II, Atg12-Atg5, Atg4, Atg5, Atg7, Atg10, Atg12, Beclin 1 were increased
and p62 was reduced in lung tissues of Cr (VI)-treated BALB/c mice. Combining,
our data demonstrated that HMGA2 plays an important role in Cr (VI)-induced
autophagy and the mechanism underlies Atg12-Atg5 conjugation modulated by HMGA2
dependent transcriptional regulation of Atg10. This suggests that HMGA2 might be
an important biomarker in Cr (VI)-induced autophagy, cell-growth or other
toxicities.
PMID- 28510368
TI - Escalator-related injuries in 30 dogs (2007-2014).
AB - OBJECTIVE: To describe a population of dogs affected by escalator-related
injuries, and to characterize the types of injuries sustained and describe
treatment administered. DESIGN: Retrospective study from March 2007 to November
2014. SETTING: Large urban referral and emergency facility. ANIMALS: Thirty
client-owned dogs presenting with injuries acquired while riding an escalator.
INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All injuries in this study
occurred secondary to entrapment of 1 or more paws in the moving parts of an
escalator; 39 paws were injured in total. The median body weight of the patients
in this study was 4.25 kg, with 73.3% of the patients weighing less than 10 kg.
Fifteen patients (50.0%) were treated surgically, the remainder were managed
conservatively. Eight patients (26.7%) underwent digit or partial-digit
amputation. Of the conservatively managed patients, 10 were treated with
bandaging of the wounds. Antimicrobials, opiate analgesics, and nonsteroidal anti
inflammatory drugs were administered in both surgically and conservatively
managed patients. CONCLUSIONS: While uncommon, escalator accidents can result in
significant injury to dogs. Measures can be taken to prevent these injuries from
occurring, whether through client education, dog training, structural
modifications in the escalators themselves, or avoidance of escalators. In the
present study, the survival rate of dogs injured on escalators was 100%.
PMID- 28510369
TI - Letter to the Editor: Radiation Injuries: Reemphasizing the Usage of Radiation
Protection Prosthesis.
AB - Sir, I write in regard to Nayar S et al article 'The Effect of a Radiation
Positioning Stent (RPS) in the Reduction of Radiation Dosage to the Opposing Jaw
and Maintenance of Mouth opening after Radiation Therapy'. I wholeheartedly agree
to that patients undergoing radio-therapy who had an Radiation Positioning Stent
(RPS) would show a significant reduction in radiation dosage to the opposing jaw
and maintained their mouth opening in the short-term. As we know that oral cancer
has emerged to be one of most deadliest cancer nowadays.
PMID- 28510370
TI - Titanium Corrosion: Implications For Dental Implants.
AB - Titanium has been considered as one of the most biocompatible metals. Studies
testing its corrosion resistance have proposed that the titanium oxide layer
formed on the metal surface is lost under certain unavoidable conditions to which
it is exposed in the oral environment. This questions its property of corrosion
resistance in the oral cavity. Hence, there is a need to understand the
mechanisms of corrosion, which can help in the long-term stability and function
of implants. Here, we review the possible pathways of corrosion of titanium in
the oral cavity, its implications and proposed methods of prevention of
corrosion.
PMID- 28510371
TI - Effect of Implant Diameter And Alloy on Peri-Implant Strain: An In Vitro
Quantitative Strain Analysis.
AB - This study aimed to evaluate the impact of implant diameter and alloy on peri
implant strains. Three implant types were investigated: regular commercially pure
titanium (RcpTi), narrow commercially pure titanium (NcpTi) and narrow titanium
zirconium alloy (NTi-Zr) implants. Strain gauge models were fabricated from epoxy
resin. All the implants were loaded in identical fashion. The greatest peri
implant strains were recorded around NTi-Zr implants, followed by NcpTi implants.
The RcpTi implants were associated with the least strain values. The difference
between the implant types was significant. Therefore, it can be concluded that
the implant diameter and material can influence the peri-implant strain
magnitude.
PMID- 28510372
TI - Does Ferrule Effect Affect Implant-Abutment Stability?
AB - PURPOSE: This study investigated the influence of placing implant-supported
crowns on the torque loss of the abutment screw before and after loading.
MATERIAL AND METHODS: Twenty implant-abutment assemblies were randomly assigned
to two groups. The first group was consisted of abutments with abutment-level
finishing line (abutment-level), and in the second group the crown margin was
placed on the implant shoulder (implant-level). Initial torque loss was recorded
for all specimens. After 500000 cyclic load of 75 N and frequency of 2 Hz, post
loading torque loss was recorded. Finite element model of each group was also
modeled and screw energy, and stress were analyzed and compared between two
groups. RESULTS: ANOVA for repeated measurements showed that the torque loss did
not change significantly after cyclic loading (P=0.73). Crown margin also had no
significant effect on the torque loss (P=0.56). However, the energy and stress of
screw in abutment-level model (4.49 mJ and 22.74 MPa) was higher than implant
level model (3.52 mJ and 20.81 MPa). CONCLUSIONS: Although embracing the implant
with crown produced less stress and energy in the abutment-implant screw, it did
not have any significant influence on the torque loss of the screw.
PMID- 28510373
TI - Acrylic Reinforcement with Off the Shelf Perforated Metal Plates.
AB - : To evaluate the effect of Dentaurum Grid Strengthener on flexural strength and
modulus of two types of PMMA, 24 beams (75 mm x 10 mm x 2.5 mm) containing bonded
and flattened Grid Strengthener and 24 beams without Grid Strengthener were
subjected to a 3-point bending test at 5 mm/min. Flexural strength and modulus
were calculated. Data were analyzed with a 2-way ANOVA. The highest mean strength
and flexural modulus was measured for reinforced high impact resin (96.2+/-14.3
MPa and 3425+/-779 MPa, respectively). For flexural strength and modulus, resin
and reinforcement had a significant effect. CLINICAL RELEVANCE: Independent of
the resin used, the incorporation of a grid strengthener increases the strength
and modulus, thus the fracture probability of dentures is reduced.
PMID- 28510374
TI - Qualitative Beam Profiling of Light Curing Units for Resin Based Composites.
AB - This study investigates two technically simple methods to determine the
irradiance distribution of light curing units that governs the performance of a
visible-light curing resin-based composites. Insufficient light irradiation leads
to under-cured composites with poor mechanical properties and elution of residual
monomers. The unknown irradiance distribution and its effect on the final
restoration are the main critical issues requiring highly sophisticated
experimental equipment. The study shows that irradiance distributions of LCUs can
easily be determined qualitatively with generally available equipment. This
significantly helps dentists in practices to be informed about the homogeneity of
the curing lights.
PMID- 28510375
TI - The Effect of Irradiation Distance on Light Transmittance and Vickers Hardness
Ratio of Two Bulk-fill Resin-based Composites.
AB - The aims of this study were to assess the light energy transmission and Vickers
hardness (VH) ratio of two bulk-fill resin-based composites (RBCs) (Tetric
EvoCeram and Filtek) cured at different distances between the light curing unit's
(LCU) tip and the surface of the restoration (T-S) using either a Bluephase G2,
Bluephase(r) 'turbo tip' or Bluephase Style LCU. Samples were cured from the top
at T-S distances of 2mm, 6mm and 10mm for 20 seconds. A MARC-Resin-CalibratorTM
recorded the transmitted irradiance reaching the bottom of the sample, in real
time. The VH was measured at the top and bottom after 24h of dark storage. Both
the total light energy (TLE) transmitted through the samples and their VH ratios
were reduced with increasing T-S distance. At 10mm T-S distance, the VH ratio
values of samples cured with Bluephase G2 LCU were significantly greater than the
samples cured with the other LCUs while the samples cured with Bluephase(r)
'turbo tip' showed the lowest values. It can be concluded that TLE transmitted
through bulk-fill RBCs and their VH ratio reduces with increasing T-S distance
but the rate of decline is LCU dependent. Bluephase G2 was associated with the
smallest light attenuation.
PMID- 28510376
TI - One-Piece Implant-Retained Mandibular Overdentures By Pre-Fabricated Titanium
Telescopic Attachments and Frictional Varnish: A Two-Year Prospective Study.
AB - Clinical efficiency of one-piece screw-type implants with telescopic were
attachments evaluated in this study. Twenty-four patients received a mandibular
implant-supported overdenture and maxillary complete denture. Ninety-six one
piece implants were inserted in the inter-foraminal area. Implants were
immediately loaded with an implant-retained overdenture and telescopic
attachments which had frictional retention elements. There was 0.25+/-0.24 mm,
0.32+/-0.25 mm, 0.43+/-0.30 mm, 0.61+/-0.30 mm and of bone resorption after 3, 6,
12 and 24 months, respectively. The need to activate the frictional retention was
the most common complication. Treatment outcomes for prefabricated telescopic
retained overdentures on one-piece implants are similar to that obtained in cases
of delayed loading.
PMID- 28510377
TI - Retrospective Study of the Survival and Patient Satisfaction with Composite Dahl
Restorations in the Management of Localised Anterior Tooth Wear.
AB - OBJECTIVE: This retrospective study was undertaken to evaluate the clinical
performance of direct composite restorations placed at an increased vertical
dimension to manage localised anterior tooth wear using the Dahl approach.
SUBJECTS AND METHODS: Two hundred and ninety six restorations were placed at an
increased OVD in 41 subjects with localized anterior Tooth Surface Loss (TSL)
were included. Survival analysis was carried out at three levels, major failure
only, minor failure only and all types of failure. Clinical follow up showed that
the posterior occlusion was reformed after a mean duration of 25.4 months (range
6 to 60 months). Mean clinical follow up of 25.4 months showed a success rate of
88.8% and survival rate of 95.6% of the restorations. The major failure rate was
4.4% while the minor failure rate was 8.7%. Patients' reported a significant
improvement in appearance, and self-confidence and reduction in sensitivity. Self
reported patient satisfaction with the procedure was high. CLINICAL RELEVANCE:
Placement of resin-based composite restorations at an increased occlusal vertical
dimension to manage localised anterior tooth wear has a good short to medium term
survival.
PMID- 28510378
TI - Replantation surgery
PMID- 28510415
TI - Smart Reinvention of the Contact Lens with Graphene.
AB - With potential benefits to the 71 million contact lens users worldwide, contact
lenses are being reinvented in the form of smart wearable electronics. In this
issue of ACS Nano, Lee et al. report on the fascinating functions of a graphene
based smart contact lens that is able to protect eyes from electromagnetic waves
and dehydration. Graphene and two-dimensional materials can be exploited in many
opportunities in the development of smart contact lenses. Here, we briefly review
and describe prospects for the future of smart contact lenses that incorporate
graphene in their platforms.
PMID- 28510417
TI - Correction to "Classics in Chemical Neuroscience: Haloperidol".
PMID- 28510416
TI - Optical Asymmetry and Nonlinear Light Scattering from Colloidal Gold Nanorods.
AB - A systematic study is presented of the intensity-dependent nonlinear light
scattering spectra of gold nanorods under resonant excitation of the longitudinal
surface plasmon resonance (SPR). The spectra exhibit features due to coherent
second and third harmonic generation as well as a broadband feature that has been
previously attributed to multiphoton photoluminescence arising primarily from
interband optical transitions in the gold. A detailed study of the spectral
dependence of the scaling of the scattered light with excitation intensity shows
unexpected scaling behavior of the coherent signals, which is quantitatively
accounted for by optically induced damping of the SPR mode through a Fermi liquid
model of the electronic scattering. The broadband feature is shown to arise not
from luminescence, but from scattering of the second-order longitudinal SPR mode
with the electron gas, where efficient excitation of the second order mode arises
from an optical asymmetry of the nanorod. The electronic-temperature-dependent
plasmon damping and the Fermi-Dirac distribution together determine the intensity
dependence of the broadband emission, and the structure-dependent absorption
spectrum determines the spectral shape through the fluctuation-dissipation
theorem. Hence a complete self-consistent picture of both coherent and incoherent
light scattering is obtained with a single set of physical parameters.
PMID- 28510418
TI - Conjugation Reaction with 8-Arm PEG Markedly Improves the Immunogenicity of
Mycobacterium tuberculosis CFP10-TB10.4 Fusion Protein.
AB - Mycobacterium tuberculosis (Mtb) is a serious fatal pathogen responsible for
tuberculosis (TB). Effective vaccination is highly desired for immunoprotection
against Mtb infection. CFP10 and TB10.4 are two important immunodominant Mtb
secreted protein antigens, which suffer from poor immunogenicity. Thus, an
antigen delivery system and adjuvants are needed to improve the immunogenicity of
the two proteins. A CFP10-TB10.4 fusion protein (CT) was used as the antigen in
the present study. Conjugation of 4-6 CT molecules in one entity with 8-arm
polyethylene glycol (PEG) acted as an antigen delivery system. Aluminum
loxoribine mixture (A-L) and poly(I:C) functioned as the adjuvants. As compared
with CT, the polymerized CT (CT-PEG) elicited significantly higher CT-specific
IgG titers, higher Th1- and Th2-type cytokines and higher percentages of CD4+ IFN
gamma+ and CD4+ IL-4+ cells in BALB/c mice. The presence of A-L and poly(I:C)
could both increase the immune response to CT-PEG. Conjugation reaction with 8
arm PEG showed a predominant driving force to improve the immunogenicity of CT.
Pharmacokinetic study in SD rats revealed that conjugation reaction with 8-arm
PEG prolonged the systemic circulation of CT and exposure to the immune system.
CT-PEG with A-L showed no apparent toxicity to organs, whereas CT-PEG with
poly(I:C) displayed some toxicity to organs. Thus, an effective and safe vaccine
against Mtb infection could be rationally designed by conjugation reaction of Mtb
secreted protein antigen with 8-arm PEG and subsequent addition of A-L.
PMID- 28510419
TI - Sunlight Promotes Fast Release of Hazardous Cadmium from Widely-Used Commercial
Cadmium Pigment.
AB - Cadmium pigments are widely used in the polymer and ceramic industry. Their
potential environmental risk is under debate, being the major barrier for
appropriate regulation. We show that 83.0 +/- 0.2% of hazardous cadmium ion
(Cd2+) was released from the commercial cadmium sulfoselenide pigment (i.e.,
cadmium red) in aqueous suspension within 24 h under simulated sunlit conditions.
This photodissolution process also generated sub-20 nm pigment nanoparticles.
Cd2+ release is attributed to the reactions between photogenerated holes and the
pigment lattices. The photodissolution process can be activated by both
ultraviolet and visible light in the solar spectrum. Irradiation under alkaline
conditions or in the presence of phosphate and carbonate species resulted in
reduced charge carrier energy or the formation of insoluble and photostable
cadmium precipitates on pigment surfaces, mitigating photodissolution. Tannic
acid inhibited the photodissolution process by light screening and scavenging
photogenerated holes. The fast release of Cd2+ from the pigment was further
confirmed in river water under natural sunlight, with 38.6 +/- 0.1% of the
cadmium released within 4 h. Overall, this study underscores the importance to
account for photochemical effects to inform risk assessments and regulations of
cadmium pigments which are currently based on their low solubility.
PMID- 28510420
TI - Nontarget Analysis Reveals a Bacterial Metabolite of Pyrene Implicated in the
Genotoxicity of Contaminated Soil after Bioremediation.
AB - Bioremediation is an accepted technology for cleanup of soil contaminated with
polycyclic aromatic hydrocarbons (PAHs), but it can increase the genotoxicity of
the soil despite removal of the regulated PAHs. Although polar biotransformation
products have been implicated as causative genotoxic agents, no specific product
has been identified. We pursued a nontarget analytical approach combining effect
directed analysis (EDA) and metabolite profiling to compare extracts of PAH
contaminated soil from a former manufactured-gas plant site before and after
treatment in a laboratory-scale aerobic bioreactor. A compound with the
composition C15H8O2 and four methylated homologues were shown to accumulate as a
result of bioreactor treatment, and the C15H8O2 compound purified from soil
extracts was determined to be genotoxic. Its structure was established by nuclear
magnetic resonance and mass spectroscopy as a heretofore unidentified alpha,beta
unsaturated lactone derived from dioxygenation of pyrene at an apical ring, 2H
naphtho[2,1,8-def]chromen-2-one (NCO), which was confirmed by synthesis. The
concentration of NCO in the bioreactor was 11 MUg g-1 dry soil, corresponding to
13% of the pyrene removed. It also accumulated in aerobically incubated soil from
two additional PAH-contaminated sites and was formed from pyrene by two pyrene
degrading bacterial cultures known to be geographically widespread, underscoring
its potential environmental significance.
PMID- 28510421
TI - Converting Carbohydrates to Carbon-Based Photocatalysts for Environmental
Treatment.
AB - Carbohydrates in biomass can be converted to semiconductive hydrothermal
carbonation carbon (HTCC), a material that contains plenty of sp2-hybridization
structures. Under solar light illumination, HTCC generates photoexcited
electrons, holes, and hydroxyl radicals. These species can be used for
photocatalytic treatment such as water disinfection and degradation of organic
pollutants. The photocatalytic activity of HTCC can be significantly enhanced by
iodine doping. The enhancement mechanism is investigated by density functional
theoretical calculations and electrochemical measurements. The iodine dopants
twist and optimize the structures of the sp2-hybridization in HTCC, thereby
favoring photon-induced excitation. Moreover, the iodine dopants facilitate the
charge transfer between different sp2-hybridization structures, thus increasing
the conductivity and activity of the HTCC. An added benefit is that the I-doped
HTCC exhibits lower cytotoxic effect than the pure HTCC. In addition to
monosaccharides (glucose), disaccharides (sucrose), and polysaccharides (starch),
we have also transformed crops (e.g., rice), plants (e.g., grass), and even
agricultural waste (e.g., straw) and animal waste (e.g., cow dung). The
conversion of carbohydrates to HTCC may be considered as a "Trash to Treasure"
approach. We believe this discovery will attract a lot of attention from
researchers involved in environmental catalysis, waste recycling, and pollution
treatment.
PMID- 28510422
TI - Encapsulation of Platinum in Fullerenes: Is That Possible?
AB - Whether transition metals can be entrapped inside fullerenes has remained unclear
for a long time. Here mass spectrometric proof of entrapment of the group VIII
transition-metal platinum (Pt) in fullerenes is first reported. Theoretical
calculations on the example of La2PtC90 show that La2Pt@C2(99915)-C90 is the most
stable isomer. Unlike other reported endohedral metal atoms, the entrapped Pt
atom is negatively charged. This work provides valuable clues for the synthesis
of some important missing endohedral metallofullerenes.
PMID- 28510423
TI - Phycocyanin-Functionalized Selenium Nanoparticles Reverse Palmitic Acid-Induced
Pancreatic beta Cell Apoptosis by Enhancing Cellular Uptake and Blocking Reactive
Oxygen Species (ROS)-Mediated Mitochondria Dysfunction.
AB - Accumulation of palmitic acid (PA) in human bodies could cause damage to
pancreatic beta cells and lead to chronic diseases by generation of reactive
oxygen species (ROS). Therefore, it is of great significance to search for
nutrition-available agents with antioxidant activity to protect pancreatic islet
cells against PA-induced damage. Phycocyanin (PC) and selenium (Se) have been
reported to have excellent antioxidant activity. In this study, PC-functionalized
selenium nanoparticles (PC-SeNPs) were synthesized to investigate the in vitro
protective effects on INS-1E rat insulinoma beta cells against PA-induced cell
death. A potent protective effect was achieved by regulation of particle size and
PC content. Among three PC-SeNPs (165, 235, and 371 nm), PC-SeNPs-235 nm showed
the highest cellular uptake and the best protective activities. For cell cycle
analysis, PC-SeNPs showed a better protective effect on PA-induced INS-1E cell
apoptosis than PC or SeNPs, and PC-SeNPs-235 nm exhibited the best effect.
Further mechanistic studies demonstrated that PA induced overproduction of
intracellular ROS, mitochondria fragmentation, activation of caspase-3, -8, and
9, and cleavage of PARP. However, pretreatment of the cells with PC-SeNPs
effectively blocked these intracellular events, which suggests that PC-SeNPs
could protect INS-1E cells against PA-induced cell apoptosis via attenuating
oxidative stress and downstream signaling pathways. This finding provides a great
promising nutritional approach for protection against diseases related to islet
damage.
PMID- 28510425
TI - Switching of Resistive Memory Behavior from Binary to Ternary Logic via
Alteration of Substituent Positioning on the Subphthalocyanine Core.
AB - Two new axially or peripherally functionalized subphthalocyanines with the
decoration of donor-acceptor substituents have been successfully synthesized,
characterized and employed in the application of resistive memory device via
solution-processable technique. Axially substituted subphthalocyanine shows
ternary resistive memory behavior with well-separated current ratios of 1:106:108
between "OFF", "ON1" and "ON2" states, while only binary logic is observed for
peripherally substituted subphthalocyanine. Computational studies show the
presence of two well-separated charge transfer states in the axially substituted
subphthalocyanine, while the charge transfer processes between the peripheral
substituents and the subphthalocyanine core are found to be very close in energy.
This work has demonstrated the impact of the substituent positioning on the
subphthalocyanine-based memory device performance, providing a new research
dimension for the future design and development of multistate organic resistive
memory.
PMID- 28510424
TI - Structure-Dependent Binding of hnRNPA1 to Telomere RNA.
AB - Telomeric repeat-containing RNA is a new noncoding RNA molecule that performs
various biofunctions. Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is an
RNA-binding protein involved in the telomere maintenance machinery. To date,
little is known about how hnRNPA1 binds to telomeric RNA. In this study, we
investigated the binding affinity and recognition mechanism of telomere RNA with
the RNA recognition motif of hnRNPA1. Using the photochemical cross-linking
method, we showed that the telomere RNA G-quadruplex with loops is important in
the interaction of telomere RNA with hnRNPA1. Using small-molecule probes, we
directly visualized the complex formed by the telomere RNA G-quadruplex and
hnRNPA1 in vitro and in live cells. The results suggested that the structure
dependent binding of hnRNPA1 to telomere RNA regulates the telomere function.
Therefore, our study provides new insights into the interactions between the RNA
G-quadruplex and proteins at the telomere.
PMID- 28510427
TI - Single Crystal Proton Conduction Study of a Metal Organic Framework of Modest
Water Stability.
AB - A sulfonated indium (In) metal organic framework (MOF) is reported with an
anionic layered structure incorporating hydrogen-bonded dimethylammonium cations
and water molecules. The MOF becomes amorphous in >60% relative humidity;
however, impedance analysis of pelletized powders revealed a proton conduction
value of over 10-3 S cm-1 at 25 degrees C and 40% RH, a very high proton
conduction value for low humidity and moderate temperature. Given the modest
humidity stability of the MOF, triaxial impedance analyses on a single crystal
was performed and confirmed bulk proton conductivity over 10-3 S cm-1 along two
axes corroborating the data from the pellet.
PMID- 28510426
TI - Multivariate Analyses of Phytoplankton Pigment Fluorescence from a Freshwater
River Network.
AB - Monitoring phytoplankton classes in river networks is critical to understanding
phytoplankton dynamics and to predicting the ecosystem response to changing land
use and seasons. Applicability of phytoplankton fluorescence as a quick and
effective ecological monitoring approach is relatively unexplored in freshwater
ecosystems. We used multivariate analyses of fluorescence from pigment extracted
in 90% acetone to assess the variability in phytoplankton classes, herbivory, and
organic matter quality in a freshwater river network. A total of four models
developed by the parallel factor analysis (PARAFAC) of fluorescence excitation
and emission matrices identified six components: Model 1 (pheophytin-A and
chlorophyll-A), Model 2 (chlorophyll-B and chlorophyll-C), Model 3 (pheophytin
B), and Model 4 (pheophytin-C). Redundancy analyses revealed that in the summer,
urban and agricultural streams were abundant in chlorophylls, fresh organic
matter, and organic nitrogen, whereas in winter, streams were high in
phaeopigments. A slow-moving, light-limited wetland stream was an exception as
high phaeopigment abundance was observed in both seasons. The PARAFAC components
were used to develop a partial least-squares regression-based model (r2 = 0.53;
Nash-Sutcliffe efficiency = 0.5; n = 147) that successfully predicted chlorophyll
A concentrations from an external subset of river water samples (r2 = 0.41; p <
0.0001; n = 75). Thus, combining multivariate analyses and fluorescence
spectroscopy is useful for monitoring and predicting phytoplankton dynamics in
large river networks.
PMID- 28510428
TI - Statistical Analysis and Prediction of Covalent Ligand Targeted Cysteine
Residues.
AB - Targeted covalent compounds or drugs have good potency as they can bind to a
specific target for a long time with low doses. Most currently known covalent
ligands were discovered by chance or by modifying existing noncovalent compounds
to make them covalently attached to a nearby reactive residue. Computational
methods for novel covalent ligand binding prediction are highly demanded. We
performed statistical analysis on protein complexes with covalent ligands
attached to cysteine residues. We found that covalent modified cysteine residues
have unique features compared to those not attached to covalent ligands,
including lower pKa, higher exposure, and higher ligand binding affinity. SVM
models were built to predict cysteine residues suitable for covalent ligand
design with prediction accuracy of 0.73. Given a protein structure, our method
can be used to automatically detect druggable cysteine residues for covalent
ligand design, which is especially useful for identifying novel binding sites for
covalent allosteric ligand design.
PMID- 28510429
TI - Copolymerization of Carbon Dioxide with Epoxides Catalyzed by Structurally Well
Characterized Dinickel Bis(benzotriazole iminophenolate) Complexes: Influence of
Carboxylate Ligands on the Catalytic Performance.
AB - A series of structurally well-defined dinickel carboxylate complexes based on the
RBiIBTP derivatives [RBiIBTP = bis(benzotriazole iminophenolate), where R = 3C
for the propyl-bridged backbone and 5C for the 2,2-dimethyl-1,3-propyl-bridged
backbone] were synthesized and developed for copolymerization of CO2 and
epoxides. The one-pot reactions of nickel perchlorate with the RBiIBTP-H2
proligands and an appropriate amount of carboxylic acid derivatives (CF3COOH or 4
X-C6H4CO2H; X = H, CF3, OMe) upon the addition of triethylamine in refluxing
methanol (MeOH) afforded dinuclear nickel dicarboxylate complexes, which could be
formulated as either [(RBiIBTP)Ni2(O2CCF3)2] (1 and 2) or [(RBiIBTP)Ni2(O2CC6H4-4
X)2] (3-7). The dinickel monobenzoate complexes [(RBiIBTP)Ni2(O2CPh)(ClO4)(H2O)]
[R = 3C (8) and 5C (9)] were prepared by using a similar synthetic route in
tetrahydrofuran under reflux with a ligand precursor to metal salt to benzoic
acid ratio of 1:2:1 in the presence of NEt3. Recrystallization of neutral nickel
perchlorate complex 8 in a saturated MeOH or ethanol (EtOH) solution gave ionic
and alcohol-solvated monobenzoate bimetallic analogues
[(3CBiIBTP)Ni2(O2CPh)(S)2]ClO4, where S = MeOH (10) and EtOH (11). Single-crystal
X-ray crystallography of dinickel analogues 1-11 indicates that the BiIBTP
scaffold performs as a N,O,N,N,O,N-hexadentate ligand to chelate two Ni atoms,
and the ancillary carboxylate group adopts a bridging bidentate bonding mode.
Catalysis for copolymerization of carbon dioxide (CO2) with cyclohexene oxide
(CHO) by complexes 1-9 was systematically investigated, and the influence of
carboxylate ligands on the catalytic behavior was also studied. Trifluoroacetate
ligated dinickel complex 1 efficiently catalyzed CO2 and CHO with a high turnover
frequency (>430 h-1) in a controlled fashion, generating perfectly alternating
poly(cyclohexenecarbonate) with large molecular weight (Mn > 50000 g/mol). In
addition to CO2/CHO copolymerization, bimetallic complex 1 was found to
effectively copolymerize CO2 with 4-vinyl-1,2-cyclohexene oxide (VCHO) or
cyclopentene oxide, producing the high carbonate contents of poly(VCHC-co-VCHO)s
and highly alternating poly(cyclopentene carbonate)s, respectively. This study
also enabled us to compare the catalytic efficiency of using cyclic epoxides with
different ring strains or functional groups as comonomers by the dinickel
catalyst 1.
PMID- 28510431
TI - Photocatalytic Hydrogen Production Using a Red-Absorbing Ir(III)-Co(III) Dyad.
AB - The synthesis of a Ir(III)-Co(III) dyad with vectorial electron transfer afforded
a novel supramolecular system that photocatalytically produces hydrogen in a
range extending from the blue region of the spectrum to the red region with
higher turnover number and frequency compared to other bimetallic dyads.
PMID- 28510430
TI - Nanoarchitecturing of Natural Melanin Nanospheres by Layer-by-Layer Assembly:
Macroscale Anti-inflammatory Conductive Coatings with Optoelectronic Tunability.
AB - Natural melanins are biocompatible conductors with versatile functionalities.
Here, we report fabrication of multifunctional poly(vinyl alcohol)/melanin
nanocomposites by layer-by-layer (LBL) assembly using melanin nanoparticles
(MNPs) directly extracted from sepia officinalis inks. The LBL assembly offers
facile manipulation of nanotextures as well as nm-thickness control of the
macroscale film by varying solvent qualities. The time-resolved absorption was
monitored during the process and quantitatively studied by fractal dimension and
lacunarity analysis. The capability of nanoarchitecturing provides confirmation
of complete monolayer formation and leads to tunable iridescent reflective colors
of the MNP films. In addition, the MNP films have durable electrochemical
conductivities as evidenced by enhanced charge storage capacities for 1000
cycles. Moreover, the MNP covered ITO (indium tin oxide) substrates significantly
reduced secretion of inflammatory cytokines, TNF-alpha, by raw 264.7 macrophage
cells compared to bare ITO, by a factor of 5 and 1.8 with and without
lipopolysaccharide endotoxins, respectively. These results highlight the
optoelectronic device-level tunability along with the anti-inflammatory
biocompatibility of the MNP LBL film. This combination of performance should make
these films particularly interesting for bioelectronic device applications such
as electroceuticals, artificial bionic organs, biosensors, and implantable
devices.
PMID- 28510432
TI - Diels-Alder Cycloaddition of Cyclopentadiene and C60 at the Extreme High
Pressure.
AB - High-pressure Diels-Alder cycloaddition reaction of fullerenes is an important
synthetic method for the thermally stable cycloadducts. The effects of high
pressure on the potential energy surfaces of Diels-Alder cycloaddition of
cyclopentadiene and C60 were studied with a recently developed approach, the
polarizable continuum model for extreme pressure (XP-PCM). It is revealed that
the high pressure reduces the activation energies and increases reaction energies
drastically, making the DA reaction more favorable. The pressure effects on the
reaction energetics can be divided into the cavitation and electronic
contributions. For the activation energy, the cavitation contribution is
significant in comparison with the electronic contribution. To assist future
experiments, the activation volume and reaction volume were computed on the basis
of the relationship between activation energy or reaction energy with the
pressure as a consequence of the fitting linear correlation between activation
energy or reaction energy with the pressure.
PMID- 28510434
TI - Mechanistic Description of Photochemical Oligomer Formation from Aqueous Pyruvic
Acid.
AB - The aqueous phase photochemistry of pyruvic acid, an important oxidation product
of isoprene, is known to generate larger oligomeric species that may contribute
to the formation of secondary organic aerosol in the atmosphere. Using high
resolution negative mode electrospray ionization mass spectrometry, the aqueous
photochemistry of dilute solutions of pyruvic acid (10, 1, and 0.5 mM) under
anaerobic conditions was investigated. Even at the lowest concentration,
covalently bonded dimers and trimers of pyruvic acid were observed as
photochemical products. We calculate that it is energetically possible to
photochemically generate parapyruvic acid, a dimer of pyruvic acid that is known
to form via dark oligomerization processes. Subsequent photochemical reactions of
parapyruvic acid with pyruvic acid form larger oligomeric products, such as 2,4
dihydroxy-2-methyl-5-oxohexanoic acid. A robust and relatively simple
photochemical mechanism is discussed that explains both the conditional
dependence and wide array of products that are observed.
PMID- 28510433
TI - Gibbs Sampler-Based lambda-Dynamics and Rao-Blackwell Estimator for Alchemical
Free Energy Calculation.
AB - lambda-dynamics is a generalized ensemble method for alchemical free energy
calculations. In traditional lambda-dynamics, the alchemical switch variable
lambda is treated as a continuous variable ranging from 0 to 1 and an empirical
estimator is utilized to approximate the free energy. In the present article, we
describe an alternative formulation of lambda-dynamics that utilizes the Gibbs
sampler framework, which we call Gibbs sampler-based lambda-dynamics (GSLD).
GSLD, like traditional lambda-dynamics, can be readily extended to calculate free
energy differences between multiple ligands in one simulation. We also introduce
a new free energy estimator, the Rao-Blackwell estimator (RBE), for use in
conjunction with GSLD. Compared with the current empirical estimator, the
advantage of RBE is that RBE is an unbiased estimator and its variance is usually
smaller than the current empirical estimator. We also show that the multistate
Bennett acceptance ratio equation or the unbinned weighted histogram analysis
method equation can be derived using the RBE. We illustrate the use and
performance of this new free energy computational framework by application to a
simple harmonic system as well as relevant calculations of small molecule
relative free energies of solvation and binding to a protein receptor. Our
findings demonstrate consistent and improved performance compared with
conventional alchemical free energy methods.
PMID- 28510435
TI - Carbenes as Electron-Pair Donors To CO2 for C...C Tetrel Bonds and C-C Covalent
Bonds.
AB - Ab initio MP2/aug'-cc-pVTZ calculations have been carried out to identify stable
complexes and molecules and the transition structures that interconvert them on
the potential surfaces of ten singlet carbene bases acting as electron-pair
donors to CO2. The carbene bases include cyclic C(NHCH)2 or NHC, C(NH2)2, an
oxygen heterocyclic carbene C(OCH)2 or OHC, C(OH)2, C(CH3)2, cyclic C3H2, CCCH2,
CCl2, CCH2, and CF2. Carbene:CO2 complexes stabilized by C...C tetrel bonds have
been found on all potential surfaces, whereas carbene-CO2 molecules stabilized by
C-C covalent bonds have been found on eight surfaces. Three of these molecules
have open structures with C2v symmetry, whereas the remaining have cyclic three
membered C-O-C rings with Cs symmetry. The transition structures which connect
the complex and the molecule are bound on three of the potential surfaces.
Whether the transition structure is bound or unbound relative to the carbene and
CO2 depends on the relationship among C-C distances at the three stationary
points on the surface. Charge-transfer interactions stabilize carbene:CO2
complexes. The primary charge transfer in complexes arises from electron donation
from the carbene lone-pair to the CO2 molecule. There is also back-donation of
charge from CO2 to the carbene in three complexes. Systematic changes in bonding
properties occur as complexes go through transition structures and become
molecules. EOM-CCSD inter- and intramolecular C-C and C-O spin-spin coupling
constants have been computed and compared for complexes and molecules. A search
of the CSD database found the (NH2)2C-CO2 structure and 17 NHC-CO2 derivatives.
Computed bond distances and angles have been compared with experimental data.
PMID- 28510436
TI - Direct Observations of Graphene Dispersed in Solution by Twilight Fluorescence
Microscopy.
AB - Graphene and graphene oxide (GO) in solution were directly observed by a newly
developed twilight fluorescence (TwiF) microscopy. A nanocarbon dispersion was
mixed with a highly concentrated fluorescent dye solution and placed in a cell
with a viewing glass at the bottom. TwiF microscopy images the nanocarbon
material floating within a few hundred MUm of the glass surface by utilizing two
optical processes to provide a faintly illuminating backlight and visualizes GO
as either a dark image by absorption and energy transfer processes or a bright
image by alternation of fluorophore chemistry and autofluorescence. Individual
graphene and GO sheets ranging from submicron to submillimeter widths were
clearly imaged at different wavelengths, which were selectable based on the dye
used. Graphene could be differentiated from GO coexisting in the same solution.
Partial transparency revealed layering and network structures. Motions in
tumbling flow were recognized in real time. An effect of changing the solvent and
the process of adhesion on the glass surface were followed in situ.
PMID- 28510437
TI - Spline Based Shape Prediction and Analysis of Uniformly Rotating Sessile and
Pendant Droplets.
AB - Prediction and analysis of the shapes of liquid-vapor interface of droplets under
the influence of external forces is critical for various applications. In this
regard, a geometric model that can capture the macroscopic shape of the liquid
vapor interface in tandem with the subtleties near the contact line, particularly
in the regime where the droplet shape deviates significantly from the idealized
spherical cap geometry, is desirable. Such deviations may occur when external
forces such as gravity or centrifugal dominate over the surface tension force.
Here we use vector parametrized cubic spline representation for axisymmetric
fluid-fluid interfaces along with a novel thermodynamic free energy minimization
based heuristic to determine the shape of liquid-vapor interface of droplets. We
show that the current scheme can easily predict the shapes of sessile and pendant
droplets under the action of centrifugal force over a broad range of surface
contact angle values and droplet sizes encountered in practical applications.
Finally, we show that the cubic spline based modeling approach makes it
convenient to perform the inverse analysis as well, i.e., predict interfacial
properties from the shape of a droplet under the action of various types of
external forces including gravity and centrifugal. We believe that this versatile
modeling approach can be extended to model droplet shapes under various other
external forces including electric and acoustic. In addition, the simple shape
analysis approach is also promising for the development of inexpensive
interfacial analysis tools such as surface tensiometers.
PMID- 28510438
TI - Complex Effects of 24:1 Sphingolipids in Membranes Containing
Dioleoylphosphatidylcholine and Cholesterol.
AB - The effects of C24:1 sphingolipids have been tested in phospholipid bilayers
containing cholesterol. Confocal microscopy, differential scanning calorimetry,
and atomic force microscopy imaging and force curves have been used. More
precisely, the effects of C24:1 ceramide (nervonoyl ceramide, nCer) were
evaluated and compared to those of C16:0 ceramide (palmitoyl ceramide, pCer) in
bilayers composed basically of dioleoylphosphatidylcholine, sphingomyelin (either
C24:1, nSM or C16:0, pSM) and cholesterol. Combination of equimolecular amounts
of C24:1 and C16:0 sphingolipids were also studied under the same conditions.
Results show that both pCer and nCer are capable of forming segregated gel
domains. Force spectroscopy data point to nCer having a lower stiffening effect
than pCer, while the presence of nSM reduces the stiffness. DSC reveals Tm
reduction by nSM in every case. Furthermore, pSM seems to better accommodate both
ceramides in a single phase of intermediate properties, while nSM partial
accommodation of ceramides generates different gel phases with higher stiffnesses
caused by interceramide cooperation. If both pSM and nSM are present, a clear
preference of both ceramides toward pSM is observed. These findings show the
sharp increase in complexity when membranes exhibit different sphingolipids of
varying N-acyl chains, which should be a common issue in an actual cell membrane
environment.
PMID- 28510439
TI - Characterization of the Isothermal Compression Behavior of LLM-172.
AB - The high-pressure behavior of 3,4-bis(4-nitro-1,2,5-oxadiazol-3-yl)-1,2,5
oxadiazole (LLM-172) has been studied to 36 GPa by Raman spectroscopy and 50 GPa
by X-ray diffraction. The Raman spectra and calculated unit-cell volumes at
select pressures show reasonable qualitative agreement with first-principles
density functional theory calculations. Raman peaks exhibit a gradual broadening
and loss of intensity upon compression to near 20 GPa. Above 20 GPa, most Raman
features disappear with the exception of modes associated with the skeletal ring
modes. These modes were found to persist (although with low intensity) to 36 GPa.
Because these modes exhibit very low compressibility over the pressure range
studied, it is speculated that the ring structure is very stable. The X-ray
diffraction suggests that while the crystal maintains an orthorhombic structure
to near 40 GPa, it gradually undergoes a decomposition/amorphization beginning
near 10 GPa. Analysis of the Raman results suggests that decomposition proceeds
through isomerization, which leads to the formation of a C-O-N-O group rather
than ring cleavage.
PMID- 28510440
TI - Fundamental Characterization of the Micellar Self-Assembly of Sophorolipid
Esters.
AB - Surfactants are ubiquitous constituents of commercial and biological systems that
function based on complex structure-dependent interactions. Sophorolipid (SL) n
alkyl esters (SL-esters) comprise a group of modified naturally derived
glycolipids from Candida bombicola. Herein, micellar self-assembly behavior as a
function of SL-ester chain length was studied. Surface tensions as low as 31.2
mN/m and critical micelle concentrations (CMCs) as low as 1.1 MUM were attained
for diacetylated SL-decyl ester (dASL-DE) and SL-octyl ester, respectively. For
deacetylated SL-esters, CMC values reach a lower limit at SL-ester chains above n
butyl (SL-BE, 1-3 MUM). This behavior of SL-esters with increasing hydrophobic
tail length is unlike other known surfactants. Diffusion-ordered spectroscopy
(DOSY) and T1 relaxation NMR experiments indicate this behavior is due to a
change in intramolecular interactions, which impedes the self-assembly of SL
esters with chain lengths above SL-BE. This hypothesis is supported by micellar
thermodynamics where a disruption in trends occurs at n-alkyl ester chain lengths
above those of SL-BE and SL-hexyl ester (SL-HE). Diacetylated (dA) SL-esters
exhibit an even more unusual trend in that CMC increases from 1.75 to 815 MUM for
SL-ester chain lengths of dASL-BE and dASL-DE, respectively. Foaming studies,
performed to reveal the macroscopic implications of SL-ester micellar behavior,
show that the observed instability in foams formed using SL-esters are due to
coalescence, which highlights the importance of understanding intermicellar
interactions. This work reveals that SL-esters are an important new family of
green high-performing surfactants with unique structure-property relationships
that can be tuned to optimize micellar characteristics.
PMID- 28510442
TI - Free Energy Landscape of Cellulose as a Driving Factor in the Mobility of
Adsorbed Water.
AB - The diffusion coefficient of water adsorbed in hydrophilic porous materials, such
as noncrystalline cellulose, depends on water activity. Faster diffusion at
higher water concentrations is observed in experimental and modeling studies. In
this paper, two asymptotic water concentrations, near-vacuum and fully saturated,
are investigated at the surface of crystalline cellulose with molecular dynamics
simulations. An increasing water concentration leads to significant changes in
the free energy landscape due to perturbation of local electrostatic potential.
Smoothening of strong energy minima, corresponding to sorption sites, and
formation of layered structure facilitates water transport in the vicinity of
cellulose. The determined transition probabilities and hydrogen bond stability
reflect the changes in the energy landscape. As a result of a concentration
increase, the emerging basins of attraction and spreading out of those existing
in the diluted state lead to an increase in water entropy. Thermal fluctuations
of cellulose are demonstrated to rearrange the landscape in the diluted limit,
increase adsorbed water entropy, and decrease the water-cellulose H-bond
lifetime.
PMID- 28510441
TI - Molybdenum Carbamate Nanosheets as a New Class of Potential Phase Change
Materials.
AB - We report for the first time the synthesis of large, free-standing, Mo2O2(MU
S)2(Et2dtc)2 (MoDTC) nanosheets (NSs), which exhibit an electron-beam induced
crystalline-to-amorphous phase transition. Both electron beam ionization and
femtosecond (fs) optical excitation induce the phase transition, which is size-,
morphology-, and composition-preserving. Resulting NSs are the largest, free
standing regularly shaped two-dimensional amorphous nanostructures made to date.
More importantly, amorphization is accompanied by dramatic changes to the NS
electrical and optical response wherein resulting amorphous species exhibit room
temperature conductivities 5 orders of magnitude larger than those of their
crystalline counterparts. This enhancement likely stems from the amorphization
induced formation of sulfur vacancy-related defects and is supported by
temperature-dependent transport measurements, which reveal efficient variable
range hopping. MoDTC NSs represent one instance of a broader class of transition
metal carbamates likely having applications because of their intriguing
electrical properties as well as demonstrated ability to toggle metal oxidation
states.
PMID- 28510443
TI - Light-Controlled Switching of a Non-photoresponsive Molecular Shuttle.
AB - In this research, we report that the acid/base-switchable molecular shuttle
without any photoresponsive group can be controlled photochemically by coupling
to the indazole-based photoacid via an intermolecular proton-transfer process.
The photocontrolled shuttling of the wheel can be conveniently monitored by
following the fluorescent evolution during the photoirradiation.
PMID- 28510445
TI - Establishment of a Direct-Injection Electron Ionization-Mass Spectrometry
Metabolomics Method and Its Application to Lichen Profiling.
AB - Direct-injection electron ionization-mass spectrometry (DI-EI-MS) is a
multivariate analysis method useful for characterizing biological materials. We
demonstrated the use of DI-EI-MS for metabolic profiling using several closely
related lichen species: Cladonia krempelhuberi, C. gracilis, C. pseudogymnopoda,
and C. ramulosa. The methodology involves conversion of total ion chromatograms
to integrated chromatograms and assessment of reproducibility. The qualitative DI
EI-MS method was used to profile the major and/or minor constituents in extracts
of lichen samples. It was possible to distinguish each lichen sample by altering
the electron energy in DI-EI-MS and examining the resulting data using one-way
analysis of variance. Previously undetectable peaks, which are easy to fragment
could be revealed by varying the electron energy. Our results suggest that
metabolic profiling using DI-EI-MS would be useful for discriminating between
subgroups within the same species. This is the first study to report the use of
DI-EI-MS in a metabolomics application.
PMID- 28510444
TI - Acetic Acid Promoted Redox Annulations with Dual C-H Functionalization.
AB - Amines such as 1,2,3,4-tetrahydroisoquinoline undergo redox-neutral annulations
with 2-alkylquinoline-3-carbaldehydes as well as the corresponding 4-alkyl
isomers and pyridine analogues. These processes involve dual C-H bond
functionalization. Acetic acid is used as a cosolvent and acts as the sole
promoter of these transformations.
PMID- 28510447
TI - Synthesis of a Highly Azide-Reactive and Thermosensitive Biofunctional Reagent
for Efficient Enrichment and Large-Scale Identification of O-GlcNAc Proteins by
Mass Spectrometry.
AB - O-linked beta-N-acetylglucosamine (O-GlcNAc) is a ubiquitous post-translational
modification of proteins in eukaryotic cells. Despite their low abundance, O
GlcNAc-modified proteins play many important roles in regulating gene expression,
signal transduction, and cell cycle. Aberrant O-GlcNAc proteins are correlated
with many major human diseases, such as Alzheimer's disease, diabetes, and
cancer. Because of the extremely low stoichiometry of O-GlcNAc proteins,
enrichment is required before mass spectrometry analysis for large-scale
identification and in-depth understanding of their cellular function. In this
work, we designed and synthesized a novel thermosensitive immobilized
triarylphosphine reagent as a convenient tool for efficient enrichment of azide
labeled O-GlcNAc proteins from complex biological samples. Immobilization of
triarylphosphine on highly water-soluble thermosensitive polymer largely
increases its solubility and reactivity in aqueous solution. As a result,
facilitated coupling is achieved between triarylphosphine and azide-labeled O
GlcNAc proteins via Staudinger ligation, due to the increased triarylphosphine
concentration, reduced interfacial mass transfer resistance, and steric hindrance
in homogeneous reaction. Furthermore, solubility of the polymer from complete
dissolution to full precipitation can be easily controlled by simply adjusting
the environmental temperature. Therefore, facile sample recovery can be achieved
by increasing the temperature to precipitate the polymer-O-GlcNAc protein
conjugates from solution. This novel immobilized triarylphosphine reagent enables
efficient enrichment and sensitive detection of more than 1700 potential O-GlcNAc
proteins from HeLa cell using mass spectrometry, demonstrating its potential as a
general strategy for low-abundance target enrichment.
PMID- 28510446
TI - Modularly Constructed Synthetic Granzyme B Molecule Enables Interrogation of
Intracellular Proteases for Targeted Cytotoxicity.
AB - Targeted therapies promise to increase the safety and efficacy of treatments
against diseases ranging from cancer to viral infections. However, the vast
majority of targeted therapeutics relies on the recognition of extracellular
biomarkers, which are rarely restricted to diseased cells and are thus prone to
severe and sometimes-fatal off-target toxicities. In contrast, intracellular
antigens present a diverse yet underutilized repertoire of disease markers. Here,
we report a protein-based therapeutic platform-termed Cytoplasmic Oncoprotein
VErifier and Response Trigger (COVERT)-which enables the interrogation of
intracellular proteases to trigger targeted cytotoxicity. COVERT molecules
consist of the cytotoxic protein granzyme B (GrB) fused to an inhibitory N
terminal peptide, which can be removed by researcher-specified proteases to
activate GrB function. We demonstrate that fusion of a small ubiquitin-like
modifier 1 (SUMO1) protein to GrB yields a SUMO-GrB molecule that is specifically
activated by the cancer-associated sentrin-specific protease 1 (SENP1). SUMO-GrB
selectively triggers apoptotic phenotypes in HEK293T cells that overexpress
SENP1, and it is highly sensitive to different SENP1 levels across cell lines. We
further demonstrate the rational design of additional COVERT molecules responsive
to enterokinase (EK) and tobacco etch virus protease (TEVp), highlighting the
COVERT platform's modularity and adaptability to diverse protease targets. As an
initial step toward engineering COVERT-T cells for adoptive T-cell therapy, we
verified that primary human T cells can express, package, traffic, and deliver
engineered GrB molecules in response to antigen stimulation. Our findings set the
foundation for future intracellular-antigen-responsive therapeutics that can
complement surface-targeted therapies.
PMID- 28510448
TI - Oxidized or Reduced Cytochrome c and Axial Ligand Variants All Form the
Apoptosome in Vitro.
AB - Cytochrome c (cyt c) has two important roles in vertebrates: mitochondrial
electron transport and activating the intrinsic cell death pathway (apoptosis).
To initiate cell death, cyt c dissociates from the inner mitochondrial membrane
and migrates to the cytosol. In the cytosol, cyt c interacts stoichiometrically
with apoptotic protease activating factor 1 (Apaf-1) and upon ATP binding induces
formation of the heptameric apoptosome. It is not clear however what the redox
state of cyt c is when it functions as the "active signal" for apoptosis. Some
reports have indicated that only ferri (i.e., oxidized Fe3+ heme) but not ferro
(reduced, Fe2+ heme) cyt c forms the apoptosome. Facilitated by our recently
described recombinant system for synthesizing novel human cyt c proteins, we use
a panel of cyt c axial ligand variants that exhibit a broad range of redox
potentials. These variants exist in different redox states. Here we show that cyt
c wild type and cyt c H19M (reduced state) and cyt c M81A and cyt c M81H
(oxidized state) all bind to Apaf-1 and form the apoptosome.
PMID- 28510450
TI - Enhancement of Antioxidative and Intestinal Anti-inflammatory Activities of
Glycated Milk Casein after Fermentation with Lactobacillus rhamnosus 4B15.
AB - In this study, we investigated the glycoproteomics of glycated milk casein (GMC)
and GMC fermented by Lactobacillus rhamnosus 4B15 (FGMC) and determined their
biological implications. There was a significant increase in the antioxidative
and anti-inflammatory activities of GMC with galactose, which were higher than
those of GMC with glucose (GMC-glc). Furthermore, the fermentation of GMC by L.
rhamnosus 4B15 synergistically enhanced the above activities compared to those of
unfermented GMC. Especially, fermented GMC-glc (FGMC-glc) possessed remarkably
improved reducing power and radical scavenging activities. Moreover, FGMC-glc
ameliorated the inflammatory response and tight junction-related intestinal
epithelial dysfunction. Additionally, hexose-derived glycation and modification
sites in protein sequences of GMC were identified. In particular, glycosylation
and sulfation of serine and threonine residues were observed, and distinct
modification sites were detected after fermentation. Therefore, these results
indicated that glycation-induced modification of casein and fermentation
correlated strongly with the enhanced functional properties.
PMID- 28510449
TI - Scalable, Electrochemical Oxidation of Unactivated C-H Bonds.
AB - A practical electrochemical oxidation of unactivated C-H bonds is presented. This
reaction utilizes a simple redox mediator, quinuclidine, with inexpensive carbon
and nickel electrodes to selectively functionalize "deep-seated" methylene and
methine moieties. The process exhibits a broad scope and good functional group
compatibility. The scalability, as illustrated by a 50 g scale oxidation of
sclareolide, bodes well for immediate and widespread adoption.
PMID- 28510451
TI - Mechanisms and Origins of Selectivities of the Lewis Acid-Catalyzed Diels-Alder
Reactions between Arylallenes and Acrylates.
AB - The mechanisms of recently reported Lewis acid-catalyzed Diels-Alder reactions of
arylallenes and acrylates were studied using density functional theory
calculations. A stepwise mechanism involving short-lived zwitterion intermediates
is established. The reaction is endo-selective in the presence of Lewis acid
catalyst. The [2 + 2] cycloaddition is not observed because of the greater charge
separation in the first step of the [2 + 2] cycloaddition. The origins of
chirality transfer in the Diels-Alder reaction using chiral arylallenes are
uncovered, and the absolute stereochemistry of the product is predicted.
PMID- 28510453
TI - Influence of Local Heating on Marangoni Flows and Evaporation Kinetics of Pure
Water Drops.
AB - The effect of localized heating on the evaporation of pure sessile water drops
was probed experimentally by a combination of infrared thermography and optical
imaging. In particular, we studied the effect of three different heating powers
and two different locations, directly below the center and edge of the drop. In
all cases, four distinct stages were identified according to the emerging thermal
patterns. In particular, depending on heating location, recirculating vortices
emerge that either remain pinned or move azimuthally within the drop. Eventually,
these vortices oscillate in different modes depending on heating location.
Infrared data allowed extraction of temperature distribution on each drop
surface. In turn, the flow velocity in each case was calculated and was found to
be higher for edge heating, due to the one-directional nature of the heating.
Additionally, calculation of the dimensionless Marangoni and Rayleigh numbers
yielded the prevalence of Marangoni convection. Heating the water drops also
affected the evaporation kinetics by promoting the "stick-slip" regime. Moreover,
both the total number of depinning events and the pinning strength were found to
be highly dependent on heating location. Lastly, we report a higher than
predicted relationship between evaporation rate and heating temperature, due to
the added influence of the recirculating flows on temperature distribution and
hence evaporation flux.
PMID- 28510452
TI - Rational Optimization of Mechanism-Based Inhibitors through Determination of the
Microscopic Rate Constants of Inactivation.
AB - Mechanism-based inhibitors (MBIs) are widely employed in chemistry, biology, and
medicine because of their exquisite specificity and sustained duration of
inhibition. Optimization of MBIs is complicated because of time-dependent
inhibition resulting from multistep inactivation mechanisms. The global kinetic
parameters kinact and KI have been used to characterize MBIs, but they provide
far less information than is commonly assumed, as shown by derivation and
simulation of these parameters. We illustrate an alternative and more rigorous
approach for MBI characterization through determination of the individual
microscopic rate constants. Kinetic analysis revealed the rate-limiting step of
inactivation of the PLP-dependent enzyme BioA by dihydro-(1,4)-pyridone 1. This
knowledge was subsequently applied to rationally design a second-generation
inhibitor scaffold with a nearly optimal maximum inactivation rate (0.48 min-1).
PMID- 28510454
TI - Kinetic Mechanism of Thioflavin T Binding onto the Amyloid Fibril of Hen Egg
White Lysozyme.
AB - Thioflavin T (ThT) is widely used as a fluorescent probe for amyloid fibril
detection. Yet the exact kinetic mechanism of ThT binding onto amyloid fibril
remains elusive. Previously reported kinetic studies using ThT-fluorescence
detected kinetic design suggested two completely different ThT-binding
mechanisms. In one study, a multistep sequential binding mechanism onto a single
ThT-binding site was suggested. In another study, a one-step parallel binding
mechanism onto multiple ThT-binding sites was suggested. The discrepancy is
likely due to the incapability of ThT-fluorescence-detected kinetic design to
differentiate the two above-mentioned mechanisms. Considering the weakness of the
ThT-fluorescence-detected approach, we investigated the ThT-binding mechanism
onto the amyloid fibril of hen egg white lysozyme (HEWL) using a new approach,
ThT-absorbance-detected kinetic design. Our new results suggest that ThT binds to
HEWL fibril through the one-step parallel binding mechanism. We hope our work can
offer some new insights into the interactions between dye molecules and amyloid
fibrils.
PMID- 28510455
TI - Clinically Relevant Multidrug Transporters Are Regulated by microRNAs along the
Human Intestine.
AB - Intestinal drug transporters are crucial determinants for absorption and oral
bioavailability of drugs. In healthy tissue donors, a recent study revealed
profound discrepancies between mRNA expression and protein abundance as well as
differences in the protein content between small and large intestine for
clinically relevant multidrug transporters as the ATP binding cassette
transporter subfamily B member 1 (ABCB1) and subfamily C member 3 (ABCC3) and the
solute carrier family 15 member 1 (SLC15A1, PEPT1). As the mechanisms underlying
these observations remained unclear, the aim of the present study was to
elucidate the intestinal regiospecific microRNA profile under physiological
conditions and identify specific microRNAs contributing to the post
transcriptional regulation of major drug transporters. For this purpose, tissue
samples were collected from six intestinal sites obtained from six healthy tissue
donors. The expression of 754 microRNAs was determined using qRT-PCR based low
density arrays, and microRNA expression levels were correlated with transporter
protein abundance quantified by targeted proteomics. A total of 241 microRNA
transporter pairs were identified, showing significant negative correlations to
protein abundance (p < 0.05). Out of these, for nine pairs, the binding of the
microRNA to the respective transporter 3'-UTR was predicted in silico. Besides
the already known interactions of miR-27a-3p-ABCB1 and miR-193a-3p-PEPT1,
reporter gene assays confirmed binding of miR-192-5p to the ABCC3 3'-UTR
(reduction of reporter gene activity by 31%; p = 0.0012), miR-409-3p to the ABCB1
3'-UTR (reduction by 38%; p = 0.0006), and miR-193b-3p as well as miR-27a-3p to
PEPT1 3'-UTR (reduction by 49% (p = 0.0012) and 20% (p = 0.0043), respectively).
These results suggest that mucosal microRNA expression contributes to the
explanation of discrepancies between mRNA expression and protein abundance as
well as site-dependent differences in protein content along the human intestine
under physiological conditions, as exemplified for ABCB1, ABCC3, and PEPT1.
PMID- 28510456
TI - Thermoresponsive Pickering Emulsions Stabilized by Silica Nanoparticles in
Combination with Alkyl Polyoxyethylene Ether Nonionic Surfactant.
AB - We put forward a simple protocol to prepare thermoresponsive Pickering emulsions.
Using hydrophilic silica nanoparticles in combination with a low concentration of
alkyl polyoxyethylene monododecyl ether (C12En) nonionic surfactant as
emulsifier, oil-in-water (o/w) emulsions can be obtained, which are stable at
room temperature but demulsified at elevated temperature. The stabilization can
be restored once the separated mixture is cooled and rehomogenized, and this
stabilization-destabilization behavior can be cycled many times. It is found that
the adsorption of nonionic surfactant at the silica nanoparticle-water interface
via hydrogen bonding between the oxygen atoms in the polyoxyethylene headgroup
and the SiOH groups on particle surfaces at low temperature is responsible for
the in situ hydrophobization of the particles rendering them surface-active.
Dehydrophobization can be achieved at elevated temperature due to weakening or
loss of this hydrogen bonding. The time required for demulsification decreases
with increasing temperature, and the temperature interval between stabilization
and destabilization of the emulsions is affected by the surfactant headgroup
length. Experimental evidence including microscopy, adsorption isotherms, and
three-phase contact angles is provided to support the mechanism.
PMID- 28510457
TI - Spatiotemporal Evolution of Coherent Elastic Strain Waves in a Single MoS2 Flake.
AB - We use bright-field imaging in an ultrafast electron microscope to
spatiotemporally map the evolution of photoexcited coherent strain waves in a
single, micrometer-size flake of MoS2. Following in situ femtosecond
photoexcitation, we observe individual wave trains emerge from discrete nanoscale
morphological features and propagate in-plane along specific wave vectors at
approximately the speed of sound (7 nm/ps). Over the span of several hundred
picoseconds, the 50 GHz wave trains (20 ps periods) are observed to undergo
phonon-phonon scattering and wave-train interference, resulting in a transition
to larger-scale, incoherent structural dynamics. This incoherent motion further
evolves into coherent nanomechanical oscillations over a few nanoseconds,
ultimately leading to megahertz, whole-flake multimode resonances having
microsecond lifetimes. These results provide insight into the low-frequency
structural response of MoS2 to relatively coherent optical photoexcitation by
elucidating the origin and the evolution of high-velocity, gigahertz strain
waves.
PMID- 28510459
TI - Efficient Round-Trip Time Optimization for Replica-Exchange Enveloping
Distribution Sampling (RE-EDS).
AB - Replica-exchange enveloping distribution sampling (RE-EDS) allows the efficient
estimation of free-energy differences between multiple end-states from a single
molecular dynamics (MD) simulation. In EDS, a reference state is sampled, which
can be tuned by two types of parameters, i.e., smoothness parameters(s) and
energy offsets, such that all end-states are sufficiently sampled. However, the
choice of these parameters is not trivial. Replica exchange (RE) or parallel
tempering is a widely applied technique to enhance sampling. By combining EDS
with the RE technique, the parameter choice problem could be simplified and the
challenge shifted toward an optimal distribution of the replicas in the
smoothness-parameter space. The choice of a certain replica distribution can
alter the sampling efficiency significantly. In this work, global round-trip time
optimization (GRTO) algorithms are tested for the use in RE-EDS simulations. In
addition, a local round-trip time optimization (LRTO) algorithm is proposed for
systems with slowly adapting environments, where a reliable estimate for the
round-trip time is challenging to obtain. The optimization algorithms were
applied to RE-EDS simulations of a system of nine small-molecule inhibitors of
phenylethanolamine N-methyltransferase (PNMT). The energy offsets were determined
using our recently proposed parallel energy-offset (PEOE) estimation scheme.
While the multistate GRTO algorithm yielded the best replica distribution for the
ligands in water, the multistate LRTO algorithm was found to be the method of
choice for the ligands in complex with PNMT. With this, the 36 alchemical free
energy differences between the nine ligands were calculated successfully from a
single RE-EDS simulation 10 ns in length. Thus, RE-EDS presents an efficient
method for the estimation of relative binding free energies.
PMID- 28510458
TI - Interplay between Hydrogen Bonding and Vibrational Coupling in Liquid N
Methylacetamide.
AB - Intrinsically disordered proteins play an important role in biology, and
unraveling their labile structure presents a vital challenge. However, the
dynamical structure of such proteins thwarts their study by standard techniques
such as X-ray diffraction and NMR spectroscopy. Here, we use a neat liquid
composed of N-methylacetamide molecules as a model system to elucidate dynamical
and structural properties similar to those one can expect to see in intrinsically
disordered proteins. To examine the structural dynamics in the neat liquid, we
combine molecular dynamics, response-function-based spectral simulations, and two
dimensional polarization-resolved infrared spectroscopy in the amide I (CO
stretch) region. The two-dimensional spectra reveal a delicate interplay between
hydrogen bonding and intermolecular vibrational coupling effects, observed
through a fast anisotropy decay. The present study constitutes a general platform
for understanding the structure and dynamics of highly disordered proteins.
PMID- 28510460
TI - Effects of Membrane Defects and Polymer Hydrophobicity on Networking Kinetics of
Vesicles.
AB - The kinetics of clustering unilamellar vesicles induced by inverse Pluronics
[poly(propylene oxide)m-poly(ethylene oxide)n-poly(propylene oxide)m, POm-EOn
POm] was investigated via experiments and molecular dynamic simulations. Two
important factors for controlling the networking kinetics are the membrane
defects, presumably located at the interfacial region between two lipid domains
induced by acyl chain mismatch, and the polymer hydrophobicity. As expected, the
clustering rate increases significantly with increasing bilayer defects on the
membrane where the insertion of PPO is likely to take place because of the
reduced energy barrier for the insertion of PO. The hydrophobic interaction
between the PO blocks and membranes with the defects region dictates the
"anchoring" kinetics, which is controlled by the association-dissociation of PO
with the lipid membrane. As a result, the dependence of clustering rate on
polymer concentration is strongly influenced by the hydrophobicity of the PO
blocks. Nevertheless, longer PO blocks show stronger association with the
membrane, resulting in faster consumption of the "active" sites made of these
defect regions (causing mostly "invalid" insertions) with increasing polymer
concentration, hence inhibiting the formation of large networking clusters, while
shorter PO blocks undergo more frequent association with/dissociation from the
defects, allowing continuous formation of larger clusters with increasing polymer
concentration. This study provides important insights into how the organization
and dynamics of a biomembrane influence its interaction with foreign amphiphilic
molecules.
PMID- 28510461
TI - Underlying Causes of Persistent and Recurrent Pneumonia in Children at a
Pulmonary Referral Hospital in Tehran, Iran.
AB - BACKGROUND: There is limited data on recurrent or persistent pneumonia in
children, particularly in the developing world. This is a retrospective, cross
sectional study of children with recurrent or persistent pneumonia admitted to
the Pediatric Department of Massih Daneshvari Hospital, Tehran, Iran. METHODS:
Children under 18 years of age, who were admitted to the hospital with pneumonia
between 2007 and 2013, were investigated to find out the prevalence of recurrent
and persistent pneumonia and to recognize their underlying diseases. Descriptive
statistics were calculated for all data. RESULTS: Out of 601 children admitted
for pneumonia, 229 (38.1%) met the criteria for recurrent or persistent
pneumonia. An underlying illness was identified in 194 patients (84.72%). The
most common underlying causes of recurrent pneumonia included aspiration syndrome
(51.75%), recurrent wheezing (20.17%), and congenital heart diseases (20.17%).
The most common underlying illness of persistent pneumonia included pulmonary
tuberculosis (38.75%), recurrent wheezing (28.75%), and aspiration syndrome
(26.25%). CONCLUSIONS: The result showed that the majority of patients with
recurrent or persistent pneumonia had an underlying illness. New strategies and
guidelines are required for early diagnosis of underlying causes of recurrent or
persistent pneumonia in children.
PMID- 28510462
TI - Anti-Plasmodial Assessment of Four Different Iranian Propolis Extracts.
AB - BACKGROUND: Eradication of malaria will depend on discovery of new intervention
tools such as anti-malarial drugs. Due to the increasing interest in the
application of propolis against significant clinical pathogenic agents, the aim
of the present investigation was to evaluate the anti-plasmodial effect of
Iranian propolis extracts against chloroquine (CQ)-sensitive Plasmodium
falciparum 3D7 and Plasmodium berghei (ANKA strain). METHODS: Crude samples of
honeybee (Apis mellifera) propolis were collected from four provinces in northern
(Kalaleh, Golestan), northeastern (Chenaran, Razavi Khorasan), central (Taleghan,
Alborz) and western (Morad Beyg, Hamedan) areas of Iran with different types of
flora. The dried propolis samples were extracted with three different solvents,
including ethanol 70% (EtOH), ethyl acetate (EA) and dichloromethane (DCM).
RESULTS: All extracts were shown to have in vitro anti-plasmodial activity with
IC50 ranging from 16.263 to 80.012 ug/mL using parasite lactate dehydrogenase
(pLDH) assay. The DCM extract of Morad Beyg propolis indicated the highest anti
plasmodial activity (IC50: 16.263 +/- 2.910 MUg/mL; P = 0.027, Kruskal-Wallis H
test). The samples were also evaluated in mice for their in vivo anti-plasmodial
effect. The curative effect against established infection (Rane test) showed that
both extracts at all doses (50, 100, and 200 mg/kgBW) produced anti-plasmodial
activity against the parasite. Furthermore, using gas chromatography-mass
spectrometry (GC-MS), the quantity of flavonoids in DCM and EtOH 70% extracts
were found to be 7.42% and 3.10%, respectively. CONCLUSION: The potent anti
plasmodial activity of both EtOH 70% and DCM extracts of the propolis of Morad
Beyg, Hamedan suggests further analyses of individual components to assess its
utilization as anti-malarial drugs.
PMID- 28510463
TI - Factors Associated with Incidence of Induced Abortion in Hamedan, Iran.
AB - BACKGROUND: There is limited reliable information on abortion in Iran, where
abortion is illegal and many women of reproductive age seek clandestine abortion
to end their unintended pregnancy. This study aims to examine the determinants of
induced abortion in the city of Hamedan, Iran. METHODS: The study utilizes recent
data from the 2015 Hamedan Survey of Fertility, conducted in a representative
sample of 3,000 married women aged 15-49 years in the city of Hamedan, Iran.
Binary logistic regression models are used to examine factors associated with the
incidence of abortion. RESULTS: Overall, 3.8% of respondents reported having had
an induced abortion in their life. Multivariate results showed that the incidence
of abortion was strongly associated with women's education, type of contraceptive
and family income level, after controlling for confounding factors. Women using
long-acting contraceptive methods, those educated under high school diploma or
postsecondary education, and those with high level of income were more likely to
report having an induced abortion. CONCLUSION: The high incidence of abortion
among less or more educated women and those with high income level signifies
unmet family planning needs among these women, which must be addressed by focused
reproductive health and family planning programs.
PMID- 28510464
TI - A Stakeholder Perspective on Diabetes Mellitus and Diabetic Retinopathy Care in
Iran; A Qualitative Study.
AB - OBJECTIVE: To assess the national health system for management of diabetes
mellitus (DM) in Iran, with particular focus on diabetic retinopathy (DR).
MATERIALS AND METHODS: In this qualitative study, the national stakeholders
related to DR and DM management system were invited to participate. Two
researchers performed interview using a semi-structured questionnaire recommended
by the World Health Organization titled "Tool for Assessment of Diabetic
Retinopathy and DM Management Systems". The questionnaire contains seven
different sections, each consisting of closed and open-ended questions, and a
final Likert-type score, ranging from 1 indicating the worst to 4 indicating the
best status. Inconsistencies were resolved through a collective decision of the
research team, followed by a focus group discussion with stakeholders at the
Ministry of Health. RESULTS: Fourteen stakeholders out of 15 total invitees were
interviewed (response rate: 93.3%). There were national priorities, defined
policies, and running programs (score = 3), but the care system should be
strengthened in terms of implementation of clinical guidelines, with specific
reference to the availability of regular screenings for DR (score = 2). The
network of care providers, health information systems, and promotional programs
were insufficient (score = 2). The health workforce and technology for DR and DM
were acceptable (scores 4 and 3, respectively); however, there were concerns
about the appropriate distribution and utilization of resources and out-of-pocket
costs paid by patients. CONCLUSION: The existence of national policies, programs,
a qualified workforce, and modern technology is promising. Nevertheless, other
aspects of the health system need to be improved to ensure access to health and
eye care for people with DM and achieve universal health coverage.
PMID- 28510465
TI - Cigarette and Water-Pipe Use in Iran: Geographical Distribution and Time Trends
among the Adult Population; A Pooled Analysis of National STEPS Surveys, 2006
2009.
AB - OBJECTIVE: To assess the geographical distribution and time trends of
manufactured cigarette and water-pipe use among Iranian adult population. METHOD:
Pooled data from four consecutive nationally and provincially representative
STEPS surveys, 2006-2009, were analyzed. Prevalence of current daily manufactured
cigarette smokers, current daily water-pipe and current daily dual users and
associated 95%CIs were estimated using complex sample analysis techniques.
RESULTS: Overall, the prevalence of current daily tobacco use, including
cigarette and water-pipe, was estimated 23.7% for men and 3.0% for women, in
which 20.2% of men and 0.8% of women were exclusively cigarette smokers, 2.7% and
2.2% were exclusively water-pipe users, and 0.6% and 0.01% smoked both cigarettes
and water-pipes. The prevalence of cigarette smoking ranged from 12.3% to 27.7%
in men and 0.1% to 1.8% in women, and was generally highest in the northwest of
the country. Conversely, the prevalence of water-pipe smoking ranged from 1.7% to
10.9% in men and 0% to 16.8% in women, and was highest in the south and
southeast. No secular trends were observed for daily cigarette smoking in either
men (P = 0.637) or women (P = 0.308) from 2006 to 2009. However, the prevalence
of water-pipe decreased slightly in women (P = 0.012) and men (P = 0.055), though
the later was not statistically significant. CONCLUSION: In Iran, widespread
geographical variation in the use of different types of tobacco products should
be taken into account when planning for tobacco prevention policies and programs.
Iran may serve as an important setting for etiological studies to examine the
effects of long-term water pipe use on diseases.
PMID- 28510466
TI - Empirical Bayesian Geographical Mapping of Occupational Accidents among Iranian
Workers.
AB - BACKGROUND: Work-related accidents are believed to be a serious preventable cause
of mortality and disability worldwide. This study aimed to provide Bayesian
geographical maps of occupational injury rates among workers insured by the
Iranian Social Security Organization. METHODS: The participants included all
insured workers in the Iranian Social Security Organization database in 2012. One
of the applications of the Bayesian approach called the Poisson-Gamma model was
applied to estimate the relative risk of occupational accidents. Data analysis
and mapping were performed using R 3.0.3, Open-Bugs 3.2.3 rev 1012 and ArcMap9.3.
RESULTS: The majority of all 21,484 investigated occupational injury victims were
male (98.3%) including 16,443 (76.5%) single workers aged 20 - 29 years. The
accidents were more frequent in basic metal, electric, and non-electric machining
jobs. About 0.4% (96) of work-related accidents led to death, 2.2% (457) led to
disability (partial and total), 4.6% (980) led to fixed compensation, and 92.8%
(19,951) of the injured victims recovered completely. The geographical maps of
estimated relative risk of occupational accidents were also provided. The results
showed that the highest estimations pertained to provinces which were mostly
located along mountain chains, some of which are categorized as deprived
provinces in Iran. CONCLUSIONS: The study revealed the need for further
investigation of the role of economic and climatic factors in high risk areas.
The application of geographical mapping together with statistical approaches can
provide more accurate tools for policy makers to make better decisions in order
to prevent and reduce the risks and adverse outcomes of work-related accidents.
PMID- 28510467
TI - Association between Physicians' Adherence to a Pharmacotherapy Guideline and
Continuity of Care for Patients with Depression and/or Anxiety Disorder.
AB - OBJECTIVE: The aim of the paper is to investigate the association between
physicians' adherence to a pharmacotherapy guideline and continuity of care for
patients with depressive and/or anxiety disorders in a collaborative care
program. METHODS: This retrospective observational study was conducted using
medical records of subjects suffering from depression and/or anxiety disorder
visited by 26 general practitioners (GP) working with Community Mental Health
Center (CMHC), who run a collaborative care program in Tehran, Iran. All patients
were visited by a general practitioner in private offices from November 2010 to
May 2013. A scoring system was utilized to assess physicians' adherence to the
pharmacotherapy guideline using medical records. Patients' continuity of care was
calculated based on the number of days of being in the collaborative care
program. To investigate the association between physicians' adherence to the
guideline and the patients' continuity of care, univariate logistic regression
analysis, multiple logistic regression analysis and parametric survival analysis
were performed using Stata version 11. RESULT: A total of 3,338 patients were
studied. Their mean age was 37 years and 81.6% were female. Being treated by a
particular GP was an important factor in patients with depressive and/or anxiety
diagnosis as well as having both diagnoses. Furthermore, higher score of
adherence to the guideline was associated with less continuity of care in
depressive patients. CONCLUSION: Being treated by certain GPs is an effective way
of retention of patients in the treatment. The results demonstrate that patients
with guideline-based pharmacotherapy need to be told about continuity of care in
community mental health program.
PMID- 28510468
TI - Diagnostic Efficacy of Coronary Artery Three-Dimensional Steady-State Free
Precession Magnetic Resonance Angiography in Comparison with Invasive Coronary
Angiography for Detecting Coronary Artery Disease.
AB - PURPOSE: To assess the diagnostic value of three-dimensional steady-state free
precession magnetic resonance angiography (3D-SSFP MRA) for detecting coronary
artery disease (CAD). MATERIALS AND METHODS: Patients suspected of CAD based on
clinical evaluation, underwent invasive coronary angiography (CAG) and Cardiac
MRA (CMRA). Collected data in favor of any CAD findings in CMRA were compared to
CAG results as the standard diagnostic method in CAD detection. Analysis was
performed on per-patient, per-vessel and per-segment bases. RESULTS: A total of
30 patients (mean age: 43 +/- 10 years, 19 men) were enrolled for analysis. On
per-patient analysis, sensitivity, specificity, positive predictive value (PPV),
negative predictive value (NPV) and area under receiver operator characteristic
(ROC) curve of CMRA for detection of coronary artery stenosis were 100% (CI95%:
75% - 100%), 50% (CI95%: 18% - 81%), 73.33% (CI95%: 46% - 90%), 100% (CI95%: 47%
100%) and 0.827, respectively. On per-vessel analysis, CMRA had a sensitivity of
89.29% (CI95%: 71%-97%), specificity of 80.56% (CI95%: 63% - 91%), PPV of 78.13%
(CI95%: 60% - 90%), NPV of 90.63% (CI95%: 74% - 98%) and area under ROC curve of
0.845. On per-segment analysis, sensitivity, specificity, PPV and NPV of CMRA for
segmental stenosis detection were 77.78% (CI95%: 60% - 89%), 87% (CI95%: 81% -
92%), 62% (CI95%: 46% - 76%), and 93.89% (CI95%: 88% - 97%), respectively. Area
under ROC curve was 0.835 on per-segment analysis. CONCLUSION: 3D SSFP CMRA
provides a promising non-invasive diagnostic tool for assessing coronary artery
disease.
PMID- 28510469
TI - Outer Dense Fiber Proteins: Bridging between Male Infertility and Cancer.
AB - BACKGROUND: The similarities between gametogenic and carcinogenesis processes
have been noted for more than decades. Among prominent similarities between these
two processes is expression of a group of antigens, namely cancer-testis antigens
in both the testes and various cancer tissues. Outer dense fiber (ODF) proteins
are testis-specific proteins localized to sperm tails and involved in sperm
motility. METHODS: We performed a computerized search of the MEDLINE/PUBMED
databases with keywords "outer dense fiber, ODF, cancer, testis, gametogenesis
and infertility". RESULTS: The results of animal and human studies show ODF
contribution to male fertility. In addition, ODFs are expressed in some cancers,
including prostate adenocarcinoma, breast cancer, chronic myeloid leukemia and
basal cell carcinoma. CONCLUSION: ODF expression analysis in cancer may pave the
way for identification of cancer biomarkers or therapeutic targets.
PMID- 28510470
TI - The Life and Career of Dr. Mansour Shamsa, A Pioneer in Public Health.
PMID- 28510471
TI - Effects of Socio-economic Status Inequality on Health Outcomes.
PMID- 28510472
TI - Dental Disaster Squad: Necessity of the Hour in Iran.
PMID- 28510473
TI - Labor Market Outcomes: Expanding the List of Patient-centered Outcomes in
Critical Care.
PMID- 28510474
TI - Increased Magnetic Resonance Imaging Signal of the Lateral Patellar Facet
Cartilage: A Functional Marker for Patellar Instability?
AB - BACKGROUND: In the knee joint, predisposition for patellar instability can be
assessed by an abnormal Insall-Salvati index, tibial tuberosity-trochlear groove
(TTTG) distance, and abnormal shape of patella and trochlea. Given the complex
anatomic features of the knee joint with varying positions of the patella during
motion, the presence of a single or even a combination of these factors does not
inevitably result in patellar instability. After trocheoplasty in patients with
trochlear dysplasia, assessment of trochlear cartilage and subchondral bone is
limited due to postoperative artifacts. Identification of presence of edema in
the patellar cartilage may be helpful to identify patellar instability before and
after surgery in these patients. PURPOSE: To determine whether increased signal
intensity of the lateral patellar facet cartilage or measurements of abnormal
patellofemoral articulation are associated with patellar instability before and
after trochleoplasty. STUDY DESIGN: Case series; Level of evidence, 4. METHODS:
Twenty-two patients with clinical diagnosis of patellar instability who underwent
trochleoplasty, with magnetic resonance imaging (MRI) of the knee before and
after surgery, were identified. The following observations and measurements were
obtained in preoperative imaging: Insall-Salvati ratio, tibial tuberosity
trochlear groove (TTTG) distance, patellar shape (Wiberg), trochlear shape
(Hepp), and edema in the lateral patellar facet cartilage. At 3 to 12 months
after surgery, the presence or absence of edema in the cartilage of the lateral
facet of the patella, the trochlear shape, and TTTG distance were reassessed.
Wilcoxon matched-pairs signed rank test and Student t test were used. Interreader
agreement was calculated as the Cohen kappa or paired Student t test. RESULTS:
Increased cartilage signal was present in 20 patients before trochleoplasty and
in 4 after trochleoplasty. Insall-Salvati ratio was greater than 1.20 in 20
patients. Patellar shape was greater than type 2 in 18 patients. Trochlear shape
was greater than type 2 in 21 patients before and 7 after trochleoplasty. Mean
TTTG distance was 14 mm before and 10 mm after surgery. When results before and
after surgery were compared, a significant difference was found for cartilage
signal, TTTG distance, and trochlear shape. Agreement for observations was
moderate to substantial, and no significant differences were found for
interreader agreement ( P > .05). CONCLUSION: Patellar cartilage at the lateral
facet of the patella can be assessed after trochleoplasty despite postoperative
artifacts in the trochlea. A decrease of patellar edema seems to be associated
with improved femoropatellar articulation. Moreover, patellar edema may be used
as a functional criterion of patellofemoral instability. This would provide
additional information compared to morphologic criteria which just describe
predisposing factors for femoropatellar instability.
PMID- 28510475
TI - Radiation-induced Angiosarcoma as a Cause of Pleural Effusion.
PMID- 28510476
TI - Looking beyond the Tip of a Tusk: Balancing the Evidence in Prognosis-related
Communication.
PMID- 28510477
TI - Performance-Based Outcomes After Anterior Cruciate Ligament Reconstruction in
Professional Athletes Differ Between Sports.
AB - BACKGROUND: Excellent outcomes have been reported for anterior cruciate ligament
(ACL) reconstruction (ACLR) in professional athletes in a number of different
sports. However, no study has directly compared these outcomes between sports.
PURPOSE: To determine if differences in performance-based outcomes exist after
ACLR between professional athletes of each sport. STUDY DESIGN: Cohort study;
Level of evidence, 3. METHODS: National Football League (NFL), National
Basketball Association (NBA), National Hockey League (NHL), and Major League
Baseball (MLB) athletes undergoing primary ACLR for an acute rupture were
identified through an established protocol of injury reports and public archives.
Sport-specific performance statistics were collected before and after surgery for
each athlete. Return to play (RTP) was defined as a successful return to the
active roster for at least 1 regular-season game after ACLR. RESULTS: Of 344
professional athletes who met the inclusion criteria, a total of 298 (86.6%)
returned to play. NHL players had a significantly higher rate of RTP (95.8% vs
83.4%, respectively; P = .04) and a shorter recovery time (258 +/- 110 days vs
367 +/- 268 days, respectively; P < .001) than athletes in all the other sports.
NFL athletes experienced significantly shorter careers postoperatively than
players in all the other sports (2.1 vs 3.2 years, respectively; P < .001). All
athletes played fewer games ( P <= .02) 1 season postoperatively, while those in
the NFL had the lowest rate of active players 2 and 3 seasons postoperatively
(60%; P = .002). NBA and NFL players showed decreased performance at season 1
after ACLR ( P <= .001). NFL players continued to have lower performance at
seasons 2 and 3 ( P = .002), while NBA players recovered to baseline performance.
CONCLUSION: The data indicate that NFL athletes fare the worst after ACLR with
the lowest survival rate, shortest postoperative career length, and sustained
decreases in performance. NHL athletes fare the best with the highest rates of
RTP, highest survival rates, longest postoperative career lengths, and no
significant changes in performance. The unique physical demand that each sport
requires is likely one of the explanations for these differences in outcomes.
PMID- 28510478
TI - Two-Tunnel Transtibial Repair of Radial Meniscus Tears Produces Comparable
Results to Inside-Out Repair of Vertical Meniscus Tears.
AB - BACKGROUND: Radial meniscus tears disrupt the circumferential fibers and thereby
compromise meniscus integrity. Historically, radial tears were often treated with
meniscectomy because of an incomplete understanding of the biomechanical
consequences of these tears, limited information regarding the biomechanical
performance of repair, and the technical difficulty associated with repair. There
is a paucity of studies on the outcomes of the repair of radial meniscus tears.
Purpose/Hypothesis: The purpose was to determine the outcomes of 2-tunnel
transtibial repair of radial meniscus tears and compare these results to the
outcomes of patients who underwent the repair of vertical meniscus tears with a
minimum of 2-year follow-up. The hypothesis was that radial and vertical meniscus
tear repair outcomes were comparable. STUDY DESIGN: Cohort study; Level of
evidence, 3. METHODS: Patients who underwent 2-tunnel transtibial pullout repair
for a radial meniscus tear were included in this study and compared with patients
who underwent inside-out repair for a vertical meniscus tear. Subjective
questionnaires were administered preoperatively and at a minimum of 2-year follow
up, including the Lysholm score, the Western Ontario and McMaster Universities
Osteoarthritis Index (WOMAC), the Short Form-12 (SF-12) physical component
summary (PCS), the Tegner activity scale, and patient satisfaction. Analysis of
covariance was used to compare postoperative outcome scores between the meniscus
repair groups while accounting for baseline scores. Adjusted mean effects
relative to the radial repair group were reported with 95% CIs. RESULTS: Twenty
seven patients who underwent 2-tunnel transtibial pullout repair for radial
meniscus tears and 33 patients who underwent inside-out repair for vertical
meniscus tears were available for follow-up at a mean of 3.5 years (range, 2.0
5.4 years). No preoperative outcome score significantly differed between the
groups. There were no significant group differences for any of the 2-year
postoperative outcome scores. Relative to the vertical repair group, the radial
repair group exhibited an adjusted mean of -0.2 (95% CI, -5.4 to 4.9), -0.6 (95%
CI, -6.6 to 5.5), and 5.1 (95% CI, -3.9 to 14.0) points on the SF-12 PCS, WOMAC,
and Lysholm scores, respectively. CONCLUSION: The 2-tunnel transtibial pullout
technique for the repair of radial meniscus tears produces similar clinical
outcomes when compared with the repair of vertical meniscus tears at a mean 3.5
years' follow-up.
PMID- 28510479
TI - Increased Expression of p22phox Mediates Airway Hyperresponsiveness in an
Experimental Model of Asthma.
AB - AIM: Chronic airway diseases such as asthma are associated with increased
production of reactive oxygen species (ROS) and oxidative stress. Endogenous
NADPH oxidases are a major source of superoxide in lung, but their underlying
role in asthma pathology is poorly understood. We sought to characterize the
involvement of NADPH oxidase in allergic asthma by studying the role of CYBA
(p22phox) in human asthma and murine house dust mite (HDM)-induced allergic
airway inflammation. RESULTS: Increased expression and localization of p22-PHOX
were observed in biopsies of asthmatic patients. HDM-treated wild-type mice
possessed elevated p22phox expression, corresponding with elevated superoxide
production. p22phox knockout (KO) mice did not induce superoxide and were
protected against HDM-induced goblet cell hyperplasia and mucus production and
HDM-induced airway hyperresponsiveness (AHR). IL-13-induced tracheal
hyperreactivity and signal transducer and activator of transcription (STAT)6
phosphorylation were attenuated in the absence of p22phox or catalase
pretreatment. INNOVATION: Our study identifies increased expression of p22phox in
lungs of asthmatic patients and in experimental model. The induced AHR and mucus
hypersecretion are a result of increased ROS from the p22phox-dependent NADPH
oxidase, which in turn activates STAT6 for the pathological feature of asthma.
CONCLUSIONS: Together with the increased p22phox expression in lungs of asthmatic
patients, these findings demonstrate a crucial role of p22phox-dependent NADPH
oxidase for the development of mucus hypersecretion and AHR in HDM-induced model
of asthma. This suggests that inhibition of functional NADPH oxidase by selective
interference of p22phox might hold a promising therapeutic strategy for the
management of asthma. Antioxid. Redox Signal. 27, 1460-1472.
PMID- 28510480
TI - Dry-Powder Inhaler Formulation of Rifampicin: An Improved Targeted Delivery
System for Alveolar Tuberculosis.
AB - BACKGROUND: The delivery of antitubercular drugs through direct lung targeting
can lead to reduction in the dose as well as side effects of the drug. In the
present investigation, carrier (lactose)-based dry-powder inhaler of rifampicin
was prepared to achieve direct targeting of the drug into the lungs. METHODS: The
dry powder inhaler formulation was prepared by simply mixing micronized
rifampicin with coarse and fine lactose preblend. Preliminary blends of the drug
were prepared with various lactose grades (Inhalac(r), Respitose,(r) and
Lactohale(r)). Rotahaler(r) and Revolizer(r) were evaluated for the performance.
The 32 factorial design was used to optimize the amount of drug (X1) and amount
of fine lactose (X2). In vitro lung deposition was carried out using Andersen
Cascade Impactor. The % cell viability studies of the formulation were carried
out using murine macrophage J774 cell lines. The in vivo toxicity was determined
using histopathology. Further in vivo pulmonary pharmacokinetics of the developed
dry-powder inhaler (DPI) formulation was carried out in comparison to the
marketed formulation in the rat lungs. RESULTS: Based on preliminary trials,
Inhalac 230 and Inhalac 400 were selected as coarse and fine lactose grades,
respectively. Rotahaler(r) exhibited better DPI performance with the evaluated
drug blends. The mass median aerodynamic diameter (MMAD) was in the range of 4.3
5.8 MUm with the maximum fine particle fraction of 28.9%. The formulation
exhibited negligible cytotoxicity on macrophage J774 cell lines with about 75%
80% cell viability at 6- and 12-hour exposure. The histopathological examination
revealed negligible toxicity of DPI in comparison to the marketed formulation.
The in vivo pulmonary pharmacokinetic studies of the DPI formulation in rats
showed higher drug concentration in lungs in comparison to the marketed
formulation. CONCLUSION: The carrier-mediated dry-powder inhaler of rifampicin
could serve as an improved and efficient system for local targeting of drugs into
the lungs.
PMID- 28510481
TI - Family Group Conferencing-Its Added Value in Mental Health Care.
AB - Worldwide, there is a growing emphasis on reducing coercion and involving social
networks in the care of mental health clients. Nurses should encourage their
clients to regain control over their lives, preferably with less coercion and
with help from their social network. During four years, a Dutch evaluation study
was deployed to determine the applicability of mobilising help from social
networks of people with psychiatric problems. Specifically the potential of
Family Group Conferencing was examined. In this discursive article the question,
'what Family Group Conferencing adds to the existing methods that aim to reduce
coercion in mental health care and promote inclusion' is addressed.
PMID- 28510483
TI - Improvement in Ventilation-Perfusion Mismatch after Bronchoscopic Lung Volume
Reduction: Quantitative Image Analysis.
AB - Purpose To evaluate whether bronchoscopic lung volume reduction (BLVR) increases
ventilation and therefore improves ventilation-perfusion (V/Q) mismatch.
Materials and Methods All patients provided written informed consent to be
included in this study, which was approved by the Institutional Review Board
(2013-0368) of Asan Medical Center. The physiologic changes that occurred after
BLVR were measured by using xenon-enhanced ventilation and iodine-enhanced
perfusion dual-energy computed tomography (CT). Patients with severe emphysema
plus hyperinflation who did not respond to usual treatments were eligible.
Pulmonary function tests, the 6-minute walking distance (6MWD) test, quality of
life assessment, and dual-energy CT were performed at baseline and 3 months after
BLVR. The effect of BLVR was assessed with repeated-measures analysis of
variance. Results Twenty-one patients were enrolled in this study (median age, 68
years; mean forced expiratory volume in 1 second [FEV1], 0.75 L +/- 0.29). After
BLVR, FEV1 (P < .001) and 6MWD (P = .002) improved significantly. Despite the
reduction in lung volume (-0.39 L +/- 0.44), both ventilation per voxel (P <
.001) and total ventilation (P = .01) improved after BLVR. However, neither
perfusion per voxel (P = .16) nor total perfusion changed significantly (P =
.49). Patients with lung volume reduction of 50% or greater had significantly
better improvement in FEV1 (P = .02) and ventilation per voxel (P = .03) than
patients with lung volume reduction of less than 50%. V/Q mismatch also improved
after BLVR (P = .005), mainly owing to the improvement in ventilation. Conclusion
The dual-energy CT analyses showed that BLVR improved ventilation and V/Q
mismatch. This increased lung efficiency may be the primary mechanism of
improvement after BLVR, despite the reduction in lung volume. (c) RSNA, 2017
Online supplemental material is available for this article.
PMID- 28510484
TI - Ethylene Signaling Is Important for Isoflavonoid-Mediated Resistance to
Rhizoctonia solani in Roots of Medicago truncatula.
AB - The root-infecting necrotrophic fungal pathogen Rhizoctoniasolani causes
significant disease to all the world's major food crops. As a model for
pathogenesis of legumes, we have examined the interaction of R. solani AG8 with
Medicago truncatula. RNAseq analysis of the moderately resistant M. truncatula
accession A17 and highly susceptible sickle (skl) mutant (defective in ethylene
sensing) identified major early transcriptional reprogramming in A17. Responses
specific to A17 included components of ethylene signaling, reactive oxygen
species metabolism, and consistent upregulation of the isoflavonoid biosynthesis
pathway. Mass spectrometry revealed accumulation of the isoflavonoid-related
compounds liquiritigenin, formononetin, medicarpin, and biochanin A in A17.
Overexpression of an isoflavone synthase in M. truncatula roots increased
isoflavonoid accumulation and resistance to R. solani. Addition of exogenous
medicarpin suggested this phytoalexin may be one of several isoflavonoids
required to contribute to resistance to R. solani. Together, these results
provide evidence for the role of ethylene-mediated accumulation of isoflavonoids
during defense against root pathogens in legumes. The involvement of ethylene
signaling and isoflavonoids in the regulation of both symbiont-legume and
pathogen-legume interactions in the same tissue may suggest tight regulation of
these responses are required in the root tissue.
PMID- 28510482
TI - Rod Outer Segment Development Influences AAV-Mediated Photoreceptor Transduction
After Subretinal Injection.
AB - Vectors based on the adeno-associated virus (AAV) are currently the preferred
tools for delivering genes to photoreceptors (PR) in small and large animals.
AAVs have been applied successfully in various models of PR dystrophies. However,
unknown barriers still limit AAV's efficient application in several forms of
severe PR degenerations due to insufficient transgene expression and/or treated
cells at the time of injection. Optimizations of PR gene therapy strategies will
likely benefit from the identification of the cellular factors that influence PR
transduction. Interestingly, recent studies have shown that the AAV transduction
profile of PRs differs significantly between neonatal and adult mouse retinas
after subretinal injection. This phenomenon may provide clues to identify host
factors that influence the efficiency of AAV-mediated PR transduction. This study
demonstrates that rod outer segments are critical modulators of efficient AAV
mediated rod transduction. During retinal development, rod transduction
correlated temporally and spatially with the differentiation order of PRs when
vectors were introduced subretinally but not when introduced intravitreally. All
subretinally injected vectors had an initial preference to transduce cones in the
absence of formed rod outer segments and then displayed a preference for rods as
the cells matured, independently of the expression cassette or AAV serotype.
Consistent with this observation, altered development of rod outer segments was
associated with a strong reduction of rod transduction and an increase in the
percentage of transduced cones by 2- to 2.8-fold. A similar increase of cone
transduction was observed in the adult retinal degeneration 1 (rd1) retina
compared to wild-type mice. These results suggest that the loss of rod outer
segments in diseased retinas could markedly affect gene transfer efficiency of
AAV vectors by limiting the ability of AAVs to infect dying rods efficiently.
This information could be exploited for the development of more efficient AAV
based PR gene delivery procedures.
PMID- 28510485
TI - Metabolomic Response to Huanglongbing: Role of Carboxylic Compounds in Citrus
sinensis Response to 'Candidatus Liberibacter asiaticus' and Its Vector,
Diaphorina citri.
AB - Huanglongbing, a destructive disease of citrus, is caused by the fastidious
bacterium 'Candidatus Liberibacter asiaticus' and transmitted by Asian citrus
psyllid, Diaphorina citri. The impact of 'Ca. L. asiaticus' infection or D. citri
infestation on Valencia sweet orange (Citrus sinensis) leaf metabolites was
investigated using gas chromatography mass spectrometry, followed by gene
expression analysis for 37 genes involved in jasmonic acid (JA), salicylic acid
(SA), and proline-glutamine pathways. The total amino acid abundance increased
after 'Ca. L. asiaticus' infection, while the total fatty acids increased
dramatically after infestation with D. citri, compared with control plants. Seven
amino acids (glycine, l-isoleucine, l-phenylalanine, l-proline, l-serine, l
threonine, and l-tryptophan) and five organic acids (benzoic acid, citric acid,
fumaric acid, SA, and succinic acid) increased in 'Ca. L. asiaticus'-infected
plants. On the other hand, the abundance of trans-JA and its precursor alpha
linolenic increased in D. citri-infested plants. Surprisingly, the double attack
of both D. citri infestation and 'Ca. L. asiaticus' infection moderated the
metabolic changes in all chemical classes studied. In addition, the gene
expression analysis supported these results. Based on these findings, we suggest
that, although amino acids such as phenylalanine are involved in citrus defense
against 'Ca. L. asiaticus' infection through the activation of an SA-mediated
pathway, fatty acids, especially alpha-linolenic acid, are involved in defense
against D. citri infestation via the induction of a JA-mediated pathway.
PMID- 28510486
TI - Advice for my chief resident.
AB - I have been privileged to have served as a division of rheumatology chief and/or
program director for 18 years and as a department of medicine chair and medicine
residency program director for another 22 years. During the latter, I collected
and codified advice for my chief residents. Selected highlights are presented as
follows.
PMID- 28510488
TI - Distinct Effects of Growth Hormone and Glutamine on Activation of Intestinal Stem
Cells.
AB - BACKGROUND: For patients with short bowel syndrome under parenteral nutrition
support, growth hormone (GH) and glutamine (GLN) have been found to help the
growth of intestinal mucosa. In this research, we studied the effects of GH and
GLN on intestinal stem cells (ISCs). METHODS: The in vitro and in vivo effects of
GH and/or GLN on ISCs were evaluated by observing the ability of ISCs to form
organoids in a Matrigel culture system. The expression levels of stemness and
differentiation markers in ISCs and organoids were assessed using quantitative
real-time polymerase chain reaction, immunofluorescence assay, and
immunohistochemistry staining. RESULTS: In vitro administration of GH activated
the stemness of ISCs, whereas GLN enhanced the expression of chromogranin A and
Muc2, which are differentiation markers in enteroendocrine and goblet cells,
respectively. Administration of GH or GLN in mice showed that GH, but not GLN,
upregulated the proliferative activity of ISCs with increased formation of crypt
organoids. In addition, GH increased the expression of Lgr5 and GLN enhanced
expression of Muc2 in the crypt fractions of the intestines in mice. CONCLUSION:
These results suggest that GH mainly enhances proliferative activities, whereas
GLN promotes the differentiation potential of ISCs.
PMID- 28510487
TI - Origin of the TTC values for compounds that are genotoxic and/or carcinogenic and
an approach for their re-evaluation.
AB - The threshold of toxicological concern (TTC) approach is a resource-effective de
minimis method for the safety assessment of chemicals, based on distributional
analysis of the results of a large number of toxicological studies. It is being
increasingly used to screen and prioritize substances with low exposure for which
there is little or no toxicological information. The first step in the approach
is the identification of substances that may be DNA-reactive mutagens, to which
the lowest TTC value is applied. This TTC value was based on the analysis of the
cancer potency database and involved a number of assumptions that no longer
reflect the state-of-the-science and some of which were not as transparent as
they could have been. Hence, review and updating of the database is proposed,
using inclusion and exclusion criteria reflecting current knowledge. A strategy
for the selection of appropriate substances for TTC determination, based on
consideration of weight of evidence for genotoxicity and carcinogenicity is
outlined. Identification of substances that are carcinogenic by a DNA-reactive
mutagenic mode of action and those that clearly act by a non-genotoxic mode of
action will enable the protectiveness to be determined of both the TTC for DNA
reactive mutagenicity and that applied by default to substances that may be
carcinogenic but are unlikely to be DNA-reactive mutagens (i.e. for Cramer class
I-III compounds). Critical to the application of the TTC approach to substances
that are likely to be DNA-reactive mutagens is the reliability of the software
tools used to identify such compounds. Current methods for this task are reviewed
and recommendations made for their application.
PMID- 28510490
TI - ?
PMID- 28510489
TI - Urban heat island (UHI) influence on secondary pollutant formation in a tropical
humid environment.
AB - : The combined action of urbanization (change in land use) and increase in
vehicular emissions intensifies the urban heat island (UHI) effect in many cities
in the developed countries. The urban warming (UHI) enhances heat-stress-related
diseases and ozone (O3) levels due to a photochemical reaction. Even though UHI
intensity depends on wind speed, wind direction, and solar flux, the
thermodynamic properties of surface materials can accelerate the temperature
profiles at the local scale. This mechanism modifies the atmospheric boundary
layer (ABL) structure and mixing height in urban regions. These changes further
deteriorate the local air quality. In this work, an attempt has been made to
understand the interrelationship between air pollution and UHI intensity at
selected urban areas located at tropical environment. The characteristics of
ambient temperature profiles associated with land use changes in the different
microenvironments of Chennai city were simulated using the Envi-Met model. The
simulated surface 24-hr average air temperatures (11 m above the ground) for
urban background and commercial and residential sites were found to be 30.81 +/-
2.06, 31.51 +/- 1.87, and 31.33 +/- 2.1oC, respectively. The diurnal variation of
UHI intensity was determined by comparing the daytime average air temperatures to
the diurnal air temperature for different wind velocity conditions. From the
model simulations, we found that wind speed of 0.2 to 5 m/sec aggravates the UHI
intensity. Further, the diurnal variation of mixing height was also estimated at
the study locations. The estimated lowest mixing height at the residential area
was found to be 60 m in the middle of night. During the same period, highest
ozone (O3) concentrations were also recorded at the continuous ambient air
quality monitoring station (CAAQMS) located at the residential area.
IMPLICATIONS: An attempt has made to study the diurnal variation of secondary
pollution levels in different study regions. This paper focuses mainly on the UHI
intensity variations with respect to percentage of land use pattern change in
Chennai city, India. The study simulated the area-based land use pattern with
local mixing height variations. The relationship between UHI intensity and mixing
height provides variations on local air quality.
PMID- 28510492
TI - Frequency of Germline BRCA1/2 Mutations in Unselected Patients With Colorectal
Cancer.
PMID- 28510491
TI - Short-Term Growth During Treatment with Inhaled Fluticasone
Propionate/Formoterol, Fluticasone and Beclomethasone Treatment.
AB - BACKGROUND: Fluticasone propionate/formoterol (FP/FORM) is a pressurized metered
dose inhaler (pMDI; Flutiform(r)) approved for use in adolescents and adults and
under development for pediatric use. OBJECTIVE: To compare short-term growth in
asthmatic children treated with FP/FORM, FP pMDI with valved holding chamber, and
beclomethasone dipropionate (BDP) in a breath-actuated device. METHODS: Children
with persistent asthma (n = 48; 5 to <12 years) participated in an assessor
blinded, randomized, three-way crossover trial with run in, wash out, and active
treatment periods, each of 2 weeks duration. Interventions were FP/FORM 100/10
MUg b.i.d. with an AeroChamber Plus(r) Flow-Vu(r) Spacer, FP pMDI (Flixotide(r))
100 MUg b.i.d. with a Volumatic(r) spacer, and extra-fine BDP breath-actuated
inhaler (Aerobec(r)/QVAR(r) Autohaler(r)) 100 MUg b.i.d. Lower leg growth rate
(LLGR) was measured by knemometry. RESULTS: The least square (LS) mean difference
in LLGR between FP/FORM and FP (per protocol population) was -0.006 mm/week (95%
CI: -0.095 to 0.084; p < 0.001 for noninferiority [noninferiority margin -0.200
mm/week]). Both treatments elicited no change from baseline off-treatment growth
rate. The LS mean treatment difference of FP/FORM versus BDP was 0.116 mm/week
(95% CI: -0.004 to 0.235; p = 0.057) and of FP versus BDP 0.163 mm/week (95% CI:
0.078-0.249; p < 0.001). Results in the full analysis population were: FP/FORM
versus FP -0.012 mm/week (95% CI: -0.080-0.056; p < 0.001); FP/FORM versus BDP
0.143 mm/week (95% CI: 0.064-0.222; p < 0.001); FP versus BDP 0.163 mm/week (95%
CI: 0.093-0.233; p < 0.001). CONCLUSIONS: FP/FORM pMDI with AeroChamber and FP
pMDI with Volumatic spacer did not affect lower leg growth, measured by
knemometry, in asthmatic children. Conversely, extra-fine BDP from a breath
actuated inhaler resulted in short-term growth suppression.
PMID- 28510493
TI - Not All BRAF-Mutant Metastatic Colorectal Cancers Are Identical: Distinct
Clinical Consequences of non-V600 BRAF Mutations.
PMID- 28510494
TI - Reply to M.S. Daniels et al.
PMID- 28510495
TI - Fatigue in Younger and Older Drivers: Effectiveness of an Alertness-Maintaining
Task.
AB - OBJECTIVE: The aim of this study was to examine the effects of an alertness
maintaining task (AMT) in older, fatigued drivers. BACKGROUND: Fatigue during
driving increases crash risk, and previous research suggests that alertness and
driving in younger adults may be improved using a secondary AMT during boring,
fatigue-eliciting drives. However, the potential impact of an AMT on driving has
not been investigated in older drivers whose ability to complete dual tasks has
been shown to decline and therefore may be negatively affected with an AMT in
driving. METHOD: Younger ( n = 29) and older drivers ( n = 39) participated in a
50-minute simulated drive designed to induce fatigue, followed by four 10-minute
sessions alternating between driving with and without an AMT. RESULTS: Younger
drivers were significantly more affected by fatigue on driving performance than
were older drivers but benefitted significantly from the AMT. Older drivers did
not demonstrate increased driver errors with fatigue, and driving did not
deteriorate significantly during participation in the AMT condition, although
their speed was significantly more variable with the AMT. CONCLUSION: Consistent
with earlier research, an AMT applied during fatiguing driving is effective in
improving alertness and reducing driving errors in younger drivers. Importantly,
older drivers were relatively unaffected by fatigue, and use of an AMT did not
detrimentally affect their driving performance. APPLICATION: These results
support the potential use of an AMT as a new automotive technology to improve
fatigue and promote driver safety, though the benefits of such technology may
differ between different age groups.
PMID- 28510496
TI - Comparison of the Treatment Guidelines for Actinic Keratosis: A Critical
Appraisal and Review.
AB - There are currently several reputable guidelines on the treatment of actinic
keratosis (AK) from groups in Canada, the United Kingdom, and Europe. These
recommendations, based on evidence or expert consensus, offer clinicians a
variety of treatment options for the different clinical presentations of AKs.
Although the guidelines are similar in some regards, variations exist in
treatment options, duration, and strength of recommendation. Some guidelines also
lack input on specific therapies and certain types of AK, such as hypertrophic or
thin presentations. The purpose of this article is to review and compare
guidelines published by Canadian, UK, and European groups for the management of
AKs in patients.
PMID- 28510497
TI - Clinical Development and Commercialization of Advanced Therapy Medicinal Products
in the European Union: How Are the Product Pipeline and Regulatory Framework
Evolving?
AB - The research and development of advanced therapy medicinal products (ATMPs) has
been active in Europe and worldwide during recent years. Yet, the number of
licensed products remains low. The main expected legal change in the near future
in the European Union (EU) concerns the regulation on clinical trials (536/2014),
which will come into force in 2018. With this new framework, a more harmonized
and swift process for approval of clinical trials is anticipated, which is
expected to support the entry of new innovations into the EU market. A survey on
ATMPs in clinical trials during 2010-2015 in the EU was conducted in order to
study the trends of ATMP development since the earlier survey published in 2012.
According to the results, the number of clinical trials using ATMPs is slowly
increasing in the EU. Yet, the focus is still in early development, and the
projects are mainly carried out by small and medium-sized enterprises, academia,
and hospitals. Oncology is the main area of clinical development. Yet, the
balance between cell-based products and gene therapy medicinal products in this
area may be changing in the future due to the new T-cell technologies. Many
limitations and challenges are identified for ATMP development, requiring
proportionate regulatory requirements. On the other hand, for such a novel field,
the developers should be active in considering possible constraints and actively
engage with authorities to look for solutions. This article provides up to-date
information on forthcoming regulatory improvements and discusses the main
challenges hampering the commercialization of ATMPs in the EU.
PMID- 28510498
TI - Deficits in go/no-go task performance in male undergraduate high-risk alcohol
users are driven by speeded responding to go stimuli.
AB - BACKGROUND: Response disinhibition plays an important role in addictive
behaviors. However, results of studies on the performance on response inhibition
tasks of individuals evidencing potentially problematic levels of alcohol
drinking are mixed. OBJECTIVES: We assessed conditions under which persons with a
relatively high risk of alcohol dependence show inhibition deficits in such tasks
and investigated the nature of those deficits. METHODS: Fifty-eight male
undergraduate students, 27 of which were high-risk drinkers according to the
Alcohol Use Disorders Identification Test, performed a go/no-go inhibition task
with differing percentages of no-go trials (50% vs. 25%), stimulus presentation
times (600 vs. 200 ms), and types of go and no-go stimuli (alcohol related vs.
unrelated). Response inhibition was indexed by response time (RT) to go trials
and response accuracy on go and no-go trials. RESULTS: There were no differences
between low- and high-risk drinkers on any of the three outcome measures under
the 600-ms stimulus presentation condition. Under the 200-ms condition, the high
risk drinkers showed faster RTs to go stimuli, and more errors on both go- and no
go trials than the low-risk drinkers, irrespective of type and percentage of no
go stimuli. However, the accuracy differences between the two groups disappeared
after controlling for the RT on go trials, suggesting a speed-accuracy trade-off.
CONCLUSION: High-risk drinkers' response inhibition deficits are not restricted
to alcohol-related cues and are especially likely to occur under conditions
prompting fast responding. These findings could be used to inform treatment,
suggesting the promotion of strategies aimed at preventing high-risk alcohol
users from making quick decisions.
PMID- 28510499
TI - George Lewith, MD, DM, FRCP, MRCGP (1950-2017).
PMID- 28510500
TI - Using "big data" to guide implementation of a web and mobile adaptive learning
platform for medical students.
AB - BACKGROUND: Adaptive learning platforms (ALPs) can revolutionize medical
education by making learning more efficient, but their potential has not been
realized because students do not use them persistently. METHODS: We applied
educational data mining methods to study United States medical students who used
an ALP called Osmosis ( www.osmosis.org ) from 1 August 2014 to 31 July 2015.
Multivariate logistic regressions modeled persistence on Osmosis as the dependent
variable and Osmosis-collected variables as predictors. RESULTS: The 6787
students included in our analysis responded to a total of 887,193 items, with
2138 (31.5%) using Osmosis persistently. Number of items per student, mobile
device use, subscription payment, and group membership were independently
associated with persisting (p < 0.001 in all models). Persistent users rated
quality more favorably (p < 0.01) but were not more confident in answer
selections (p = 0.80). While persisters were more accurate than non-persisters
(55% (SD 18%) vs 52% (SD 22%), p < 0.001), after adjusting for number of items,
lower accuracy was associated with persistent use (OR 0.93 [95% CI 0.90-0.97], p
< 0.01). CONCLUSIONS: Our study of a large sample of U.S. medical students
illustrates big data medical education research and provides guidance for
improving implementation of ALPs and further investigation.
PMID- 28510501
TI - Mechanical ventilation in the acute respiratory distress syndrome.
AB - The management of the acute respiratory distress syndrome (ARDS) patient is
fundamental to the field of intensive care medicine, and it presents unique
challenges owing to the specialized mechanical ventilation techniques that such
patients require. ARDS is a highly lethal disease, and there is compelling
evidence that mechanical ventilation itself, if applied in an injurious fashion,
can be a contributor to ARDS mortality. Therefore, it is imperative for any
clinician central to the care of ARDS patients to understand the fundamental
framework that underpins the approach to mechanical ventilation in this special
scenario. The current review summarizes the major components of the mechanical
ventilation strategy as it applies to ARDS.
PMID- 28510503
TI - Are we becoming inaccessible caregivers?
AB - This essay is a personal reflection of my mindset as a caregiver, and how that
has evolved throughout my training.
PMID- 28510502
TI - The Impact of Steroidal Glycoalkaloids on the Physiology of Phytophthora
infestans, the Causative Agent of Potato Late Blight.
AB - Steroidal glycoalkaloids (SGAs) are plant secondary metabolites known to be toxic
to animals and humans and that have putative roles in defense against pests. The
proposed mechanisms of SGA toxicity are sterol-mediated disruption of membranes
and inhibition of cholinesterase activity in neurons. It has been suggested that
phytopathogenic microorganisms can overcome SGA toxicity by enzymatic
deglycosylation of SGAs. Here, we have explored SGA-mediated toxicity toward the
invasive oomycete Phytophthora infestans, the causative agent of the late blight
disease in potato and tomato, as well as the potential for SGA deglycosylation by
this species. Our growth studies indicate that solanidine, the nonglycosylated
precursor of the potato SGAs alpha-chaconine and alpha-solanine, has a greater
physiological impact than its glycosylated forms. All of these compounds were
incorporated into the mycelium, but only solanidine could strongly inhibit the
growth of P. infestans in liquid culture. Genes encoding several glycoside
hydrolases with potential activity on SGAs were identified in the genome of P.
infestans and were shown to be expressed. However, we found no indication that
deglycosylation of SGAs takes place. We present additional evidence for apparent
host-specific adaptation to potato SGAs and assess all results in terms of future
pathogen management strategies.
PMID- 28510504
TI - Cardiopulmonary Exercise Testing: Basics of Methodology and Measurements.
AB - Cardiopulmonary exercise testing adds measurement of ventilation and volume of
oxygen uptake and exhaled carbon dioxide to routine physiological and performance
parameters obtainable from conventional exercise testing, furnishing an all
around vision of the systems involved in both oxygen transport from air to
mitochondria and its use during exercise. Peculiarities of cardiopulmonary
exercise testing methodology are the use of ramp protocols and calibration
procedures for flow meters and gas analyzers. Among the several parameters
provided by this technique, peak oxygen uptake, first and second ventilatory
thresholds, respiratory exchange ratio, oxygen pulse, slope of ventilation
divided by exhaled carbon dioxide relationship, exercise oscillatory ventilation,
circulatory power, and partial pressure of end-tidal carbon dioxide are among the
most relevant in the clinical setting. The choice of parameters to be considered
will depend on the indication to cardiopulmonary exercise testing in the
individual subject or patient, namely, exercise tolerance assessment, prognostic
stratification, training prescription, treatment efficacy evaluation, diagnosis
of causes of unexplained exercise tolerance reduction, or exercise
(patho)physiology evaluation for research purposes. Overall, cardiopulmonary
exercise testing is a methodology now widely available and supported by sound
scientific evidence. Despite this, its potential still remains largely underused.
Strong efforts and future investigations are needed to address these issues and
further promote the use of cardiopulmonary exercise testing in the clinical and
research setting.
PMID- 28510507
TI - Five Steps to Engage in the Concept of Whole Health Begins With Mental Health.
PMID- 28510506
TI - Signaling at the Crossroads: Matrix-Derived Proteoglycan and Reactive Oxygen
Species Signaling.
AB - SIGNIFICANCE: Proteoglycans (PGs), besides their structural contribution, have
emerged as dynamic components that mediate a multitude of cellular events. The
various roles of PGs are attributed to their structure, spatial localization, and
ability to act as ligands and receptors. Reactive oxygen species (ROS) are small
mediators that are generated in physiological and pathological conditions.
Besides their reactivity and ability to induce oxidative stress, a growing body
of data suggests that ROS signaling is more relevant than direct radical damage
in development of human pathologies. Recent Advances: Cell surface transmembrane
PGs (syndecans, cluster of differentiation 44) represent receptors in diverse and
complex transduction networks, which involve redox signaling with implications in
cancer, fibrosis, renal dysfunction, or Alzheimer's disease. Through NADPH
oxidase (NOX)-dependent ROS, the extracellular PG, hyaluronan is involved in
osteoclastogenesis and cancer. The ROS sources, NOX1 and NOX4, increase biglycan
induced inflammation, while NOX2 is a negative regulator. CRITICAL ISSUES: The
complexity of the mechanisms that bring ROS into the light of PG biology might be
the foundation of a new research area with significant promise for understanding
health and disease. Important aspects need to be investigated in PG/ROS
signaling: the discovery of specific targets of ROS, the precise ROS-induced
chemical modifications of these targets, and the study of their pathological
relevance. FUTURE DIRECTIONS: As we become more and more aware of the
interactions between PG and ROS signaling underlying intracellular communication
and cell fate decisions, it is quite conceivable that this field will allow to
identify new therapeutic targets.-Antioxid. Redox Signal. 27, 855-873.
PMID- 28510505
TI - Papillary Thyroid Cancer: The Good and Bad of the "Good Cancer".
AB - BACKGROUND: Papillary thyroid cancer is often described as the "good cancer"
because of its treatability and relatively favorable survival rates. This study
sought to characterize the thoughts of papillary thyroid cancer patients as they
relate to having the "good cancer." METHODS: This qualitative study included 31
papillary thyroid cancer patients enrolled in an ongoing randomized trial. Semi
structured interviews were conducted with participants at the preoperative visit
and two weeks, six weeks, six months, and one year after thyroidectomy. Grounded
theory was used, inductively coding the first 113 interview transcripts with
NVivo 11. RESULTS: The concept of thyroid cancer as "good cancer" emerged
unprompted from 94% (n = 29) of participants, mostly concentrated around the time
of diagnosis. Patients encountered this perception from healthcare providers,
Internet research, friends, and preconceived ideas about other cancers. While
patients generally appreciated optimism, this perspective also generated negative
feelings. It eased the diagnosis of cancer but created confusion when individual
experiences varied from expectations. Despite initially feeling reassured,
participants described feeling the "good cancer" characterization invalidated
their fears of having cancer. Thyroid cancer patients expressed that they did not
want to hear that it's "only thyroid cancer" and that it's "no big deal," because
"cancer is cancer," and it is significant. CONCLUSIONS: Patients with papillary
thyroid cancer commonly confront the perception that their malignancy is "good,"
but the favorable prognosis and treatability of the disease do not
comprehensively represent their cancer fight. The "good cancer" perception is at
the root of many mixed and confusing emotions. Clinicians emphasize optimistic
outcomes, hoping to comfort, but they might inadvertently invalidate the impact
thyroid cancer has on patients' lives.
PMID- 28510509
TI - Psychometric Properties of the Psychological Vulnerability Scale in Higher
Education Students.
AB - BACKGROUND: Psychological vulnerability is related to cognitive beliefs that
reflect dependence on one's sense of self-worth and to maladaptive functioning.
It is a disadvantage that renders people less protected to face negative life
experiences. OBJECTIVE: The purpose of this study was to adapt and test the
psychometric properties of the Psychological Vulnerability Scale in a sample of
267 Portuguese higher education students. DESIGN: A psychometric study of the
Psychological Vulnerability Scale, after translation into Portuguese, was
performed with a convenience sample of higher education students. Participants
were asked to fill in the sociodemographic questionnaire, the Psychological
Vulnerability Scale, the Brief Symptom Inventory, and a one-item question about
the Perception of Vulnerability. RESULTS: The mean age of the participants was
20.5 years ( SD = 3.3). A factor analysis confirmed the original one-factor
structure, explaining 42.9% of the total variance. The Psychological
Vulnerability Scale showed adequate internal consistency and excellent test
retest stability. Convergent validity was confirmed by positive correlations with
the Brief Symptom Inventory and Perception of Vulnerability. CONCLUSIONS:
Overall, the Psychological Vulnerability Scale showed good validity, reliability,
and stability over time. The Psychological Vulnerability Scale is now ready to be
used by practitioners and researchers to measure the psychological vulnerability
among Portuguese higher education students. These data add to the body of
knowledge of psychiatric and mental health nursing and provides support for the
use of the Psychological Vulnerability Scale in higher education students.
PMID- 28510510
TI - A Nurse Practitioner's View on Telehealth.
PMID- 28510511
TI - Corrigendum.
AB - Birkeland AC, Owen JH, Prince ME. 2015. Targeting head and neck cancer stem
cells: current advances and future challenges. J Dent Res. 94(11):1516-1523.
(Original DOI: 10.1177/0022034515601960) In this article, the funding source was
not declared. The Acknowledgments have been updated in the online article as
follows: Andrew Birkeland is a Research Fellow funded on a T32 Advanced Research
Training in Otolaryngology Program Training Grant (T32 DC005356) funded by the
National Institutes of Health NIDCD (National Institute On Deafness And Other
Communication Disorders).
PMID- 28510514
TI - Door Is Open for HRAs to Make a Comeback.
AB - For four years, businesses that wanted to reimburse employees for their health
insurance premiums rather than buying their coverage for them were told that that
was no longer allowed under the ACA. But the health reimbursement arrangement
(HRA) is back, brought back to life by provisions tucked into last year's 21st
Century Cure Act.
PMID- 28510512
TI - Field trial of insect-resistant and herbicide-tolerant genetically modified
cotton (Gossypium hirsutum L.) for environmental risk assessment in Japan.
AB - Japan imports cottonseed mainly from Australia and the USA where more than 96% of
all cotton varieties grown are genetically modified (GM). GM crops undergo an
environmental risk assessment (ERA) under the Law Concerning the Conservation and
Sustainable Use of Biological Diversity before import into Japan. Potential
adverse effects on biodiversity are comprehensively assessed based on
competitiveness, production of harmful substances and outcrossing ability. Even
though imported cottonseed is intended for food and feed uses and not for
cultivation, the potential risks from seed spillage during transport must be
evaluated. In most cases, the ERA requires data collected from in-country field
trials to demonstrate how the GM crop behaves in Japan's environment. Confined
field trials in Japan were conducted for the ERA of Lepidoptera-resistant and
glufosinate-tolerant GM cotton (Gossypium hirsutum L.) lines GHB119 and T304-40.
These lines were compared with conventional varieties for growth habit,
morphological characteristics, seed dormancy, and allelopathic activity
associated with competitiveness and production of harmful substances. Outcrossing
ability was not a concern due to the absence of sexually compatible wild
relatives in Japan. Although slight statistical differences were observed between
the GM line and its conventional comparator for some morphological
characteristics, transgenes or transformation were not considered to be
responsible for these differences. The trial demonstrated that competitiveness
and production of harmful substances by these GM cotton lines were equivalent to
conventional cotton varieties that have a long history of safe use, and no
potential adverse effects to biosafety in Japan were observed.
PMID- 28510515
TI - Biosimilars Ready, At Last, To Make Their Entrance: Stars Are Born or Do They
Fizzle?
AB - The future of biosimilars in this country is nothing if not uncertain. Most
immediately, the U.S. Supreme Court is hearing a case that will determine the
timing of the 180-day waiting period before a biosimilar can go on the market.
But there are larger and longer-term issues at play as well.
PMID- 28510516
TI - The Biosimilar Pipeline Seams Seem To Be Bursting.
AB - The biosimilar segment of the pharmaceutical industry is on fire. Some 700
biosimilars are at some stage of development, and more than 660 companies are
involved in some way in the biosimilars land rush. Still, only a handful may get
on the market in the next few years.
PMID- 28510513
TI - Putative roles as oncogene or tumour suppressor of the Mid-clustered microRNAs in
Gallid alphaherpesvirus 2 (GaHV2) induced Marek's disease lymphomagenesis.
AB - In the last decade, numerous microRNAs (miRNAs) have been identified in diverse
virus families, particularly in herpesviruses. Gallid alphaherpesvirus 2 (GaHV2)
is a representative oncogenic alphaherpesvirus that induces rapid-onset T-cell
lymphomas in its natural hosts, namely Marek's disease (MD). In the GaHV2 genome
there are 26 mature miRNAs derived from 14 precursors assembled into three
clusters, namely the Meq-cluster, Mid-cluster and LAT-cluster. Several GaHV2
miRNAs, especially those in the Meq-cluster (e.g. miR-M4-5p), have been
demonstrated to be critical in MD pathogenesis and/or tumorigenesis.
Interestingly the downstream Mid-cluster is regulated and transcribed by the same
promoter as the Meq-cluster in the latent phase of the infection, but the role of
these Mid-clustered miRNAs in GaHV2 biology remains unclear. We have generated
the deletion mutants of the Mid-cluster and of its associated individual miRNAs
in GX0101 virus, a very virulent GaHV2 strain, and demonstrated that the Mid
clustered miRNAs are not essential for virus replication. Using GaHV2-infected
chickens as an animal model, we found that, compared with parental GX0101 virus,
the individual deletion of miR-M31 decreased the mortality and gross tumour
incidence of infected chickens while the deletion individually of miR-M1 or miR
M11 unexpectedly increased viral pathogenicity or oncogenicity, similarly to the
deletion of the entire Mid-cluster region. More importantly, our data further
confirm that miR-M11-5p, the miR-M11-derived mature miRNA, targets the viral
oncogene meq and suppresses its expression in GaHV2 infection. We report here
that members of the Mid-clustered miRNAs, miR-M31-3p and miR-M11-5p, potentially
act either as oncogene or tumour suppressor in MD lymphomagenesis.
PMID- 28510517
TI - Biosimilars in Oncology: Reality Could Bite the Copycats, Dog Potential Major
Savings.
AB - No one knows how much of an effect biosimilars will have on oncology
expenditures. Pricing and market share are in a large, opaque "to be determined"
cloud. But there's certainly potential for a major impact that could lower
oncology expenditures by millions, if not billions.
PMID- 28510518
TI - Biosimilar Makers Hope Court Starts 6-Month Wait Sooner.
AB - The dispute centers on dueling interpretations of the Biologics Price Competition
and Innovation Act, which says a company seeking to sell a biosimilar must give
the maker of the brand-name biologic at least a 180-day notice before selling its
drug.
PMID- 28510519
TI - Health Insurers Often Foot Bill When Drug Coupons Are Used.
AB - While coupons help individual consumers, they are also having a major impact on
the insurance industry and anyone responsible for paying health care bills.
Insurers and pharmacy benefit managers complain that they foil formularies and
other pricing strategies designed to steer consumers to less-expensive drugs.
PMID- 28510520
TI - Novel Devices for Delivering Diabetes Medications: Their Value and Some Coverage
Considerations.
AB - Insurers should consider covering new drug-delivery devices that can improve
outcomes while lowering disease-specific pharmacy and long-term overall health
care costs. Managing these devices in the pharmacy benefit will consolidate
volume-based purchasing and capitalize on PBM strategies for improving adherence.
PMID- 28510521
TI - A Seer of Trump's Coming Parses Repeal and Replace.
AB - Diana Furchtgott-Roth, a senior fellow at the Manhattan Institute, a freemarket
think tank, confidently predicted back in October what few people saw coming
Donald Trump's electoral victory. Now she gives her take on the dismantling of
the ACA and what might come after.
PMID- 28510522
TI - Managed Care Reader Poll: Readers Believe Biosimilars Will Be Effective Against
Costs.
AB - In an online survey of readers conducted in late January and early February, 20%
of the 113 respondents indicated that they believed that biosimilars will be
highly effective in lowering drug costs, and the reader ratings of their
effectiveness skewed toward positive.
PMID- 28510523
TI - New Solutions for Curbing Runaway Drug Costs.
AB - Long at odds, the interests of payers and providers are becoming more compatible
and aligned. Both stakeholders need to collaborate to manage costs. Encouraging
use of generics and biosimilars is one way they can slow down the soaring drug
spend.
PMID- 28510524
TI - Lost in Translation: Why patient-friendly communication strategies are more
important than ever.
AB - Efforts to improve patient communication must become a priority. Too often, the
language we use in health care is a kind of code that serves billing and other
purposes. Jargon may be an efficient and precise way for insiders to communicate,
but it is impossible for patients to understand.
PMID- 28510525
TI - $850 Per Bowel Movement?! Hard To Justify That Cost.
AB - Constipation can be a serious and painful problem, and we shouldn't dismiss other
people's suffering. On the other hand there's a danger when new medications are
compared against placebo rather than against over-the-counter products with a
history of effectiveness.
PMID- 28510526
TI - With 'Repeal and Replace,' the Triple Aim Needed More Than Ever.
AB - The Triple Aim hit a nerve with medical directors and health care managers of all
kinds. That's because it is a concise way of summarizing the disparate issues
that anyone trying to manage the delivery and cost of health care must deal with.
PMID- 28510527
TI - The seesaw of CVD: Deaths down, costs up.
AB - Coronary heart disease deaths will decline by 30% between 2010 and 2020 because
of improvement in "cardiovascular health metrics" (avoidance of smoking, more
physical activity, and so on). But this less-deadly era of CVD is going to be a
more costly one, with direct medical costs of CVD more than doubling by 2030 to
$918 billion from $396 billion in 2012.
PMID- 28510529
TI - Perspectives.
PMID- 28510530
TI - Effects of bulk and surface defects on the photocatalytic performance of size
controlled TiO2 nanoparticles.
AB - Defects are one of the crucial factors influencing the photocatalytic activities
of TiO2 nanoparticles (NPs), as they directly affect the charge separation
efficiencies. However, we found that the effect of bulk or surface defects on the
photocatalytic performance of TiO2 is totally different. Here, we controllably
synthesized four kinds of uniform TiO2 NPs, which were used to investigate how
the bulk and surface defects influenced the photoactivities of samples with
different particle sizes. Through XPS and EPR analysis, bulk and surface defects
were observed in all the TiO2 samples and their amounts had been reduced after
the calcination process. The reduction of bulk and surface defects enhanced the
photoactivities of TiO2 NPs with diameters >10 nm, but the situation was inverse
for those samples with diameters <10 nm. Therefore, we demonstrated that bulk
defects play a dominate role in the change in photoactivity in particles larger
than 10 nm, while surface defects are more important than bulk defects for
particles less than 10 nm.
PMID- 28510531
TI - Oriented epitaxial TiO2 nanowires for water splitting.
AB - Highly oriented epitaxial rutile titanium dioxide (TiO2) nanowire arrays have
been hydrothermally grown on polycrystalline TiO2 templates with their
orientation dependent on the underlying TiO2 grain. Both the diameter and areal
density of the nanowires were tuned by controlling the precursor concentration,
and the template surface energy and roughness. Nanowire tip sharpness was
influenced by precursor solubility and diffusivity. A new secondary ion mass
spectrometer technique has been developed to install additional nucleation sites
in single crystal TiO2 templates and the effect on nanowire growth was probed.
Using the acquired TiO2 nanowire synthesis knowhow, an assortment of nanowire
arrays were installed upon the surface of undoped TiO2 photo-electrodes and
assessed for their photo-electrochemical water splitting performance. The key
result obtained was that the presence of short and dispersed nanowire arrays
significantly improved the photocurrent when the illumination intensity was
increased from 100 to 200 mW cm-2. This is attributed to the alignment of the
homoepitaxially grown nanowires to the [001] direction, which provides the
fastest charge transport in TiO2 and an improved pathway for photo-holes to find
water molecules and undertake oxidation. This result lays a foundation for
achieving efficient water splitting under conditions of concentrated solar
illumination.
PMID- 28510532
TI - Scattering and plasmonic synergetic enhancement of the performance of dye
sensitized solar cells by double-shell SiO2@Au@TiO2 microspheres.
AB - The Au nanoparticle sandwich double spheric-shells of SiO2@Au@TiO2 (SAT)
microspheres are synthesized. The significant influence of the SAT microspheres
on the properties of dye-sensitized solar cells (DSSCs) is investigated. Studies
indicate that the introduction of SAT markedly enhanced the light scattering and
capture ability of DSSCs and thus photogenerated electrons. DSSCs doped with 2.25
wt% SAT exhibit a maximum short circuit current density of 17.0 mA cm-2 and
photoelectric conversion efficiency of 7.14%, which are remarkably higher than
those of conventional DSSCs at 15.7% and 21.2%, respectively. The marked
enhancement in the performance of the optimal DSSCs can be attributed to the
synergetic complementary effect of the enhanced light scattering of the
microspheres and to the localized surface plasmon resonance of the Au
nanoparticles in the SAT, and is a novel promising way of enhancing the
performance of DSSCs.
PMID- 28510533
TI - Coordination polymer nanocapsules prepared using metal-organic framework
templates for pH-responsive drug delivery.
AB - A facile, efficient, and versatile approach is presented to synthesize pH
responsive nanocapsules (~120 nm) by combining the advantages of metal-organic
frameworks (MOFs) and metal-organic thin films. ZIF-8 nanoparticles are used as
templates on which a thin film coating of iron(III)-catechol complexes is derived
from the coordination between dopamine-modified alginate (AlgDA) and iron(III)
ions. After the template removal, nanocapsules with a pH-responsive wall are
obtained. Doxorubicin (Dox), a typical anticancer drug, is first immobilized in
ZIF-8 frameworks through coprecipitation and then encapsulated in nanocapsules
after the removal of ZIF-8. The structure of the iron(III)-catechol complex
varies with pH value, thus conferring the Dox@Nanocapsules with tailored release
behavior in vitro. Cytotoxicity tests illustrate the highly effective
cytotoxicity of Dox@Nanocapsules towards cancer cells. This study provides a new
method for preparing smart nanocapsules and offers more opportunities for the
controlled delivery of drugs.
PMID- 28510528
TI - Identification of octopaminergic neurons that modulate sleep suppression by male
sex drive.
AB - Molecular and circuit mechanisms for balancing competing drives are not well
understood. While circadian and homeostatic mechanisms generally ensure
sufficient sleep at night, other pressing needs can overcome sleep drive. Here,
we demonstrate that the balance between sleep and sex drives determines whether
male flies sleep or court, and identify a subset of octopaminergic neurons (MS1)
that regulate sleep specifically in males. When MS1 neurons are activated,
isolated males sleep less, and when MS1 neurons are silenced, the normal male
sleep suppression in female presence is attenuated and mating behavior is
impaired. MS1 neurons do not express the sexually dimorphic FRUITLESS (FRU)
transcription factor, but form male-specific contacts with FRU-expressing
neurons; calcium imaging experiments reveal bidirectional functional connectivity
between MS1 and FRU neurons. We propose octopaminergic MS1 neurons interact with
the FRU network to mediate sleep suppression by male sex drive.
PMID- 28510534
TI - Three fundamental devices in one: a reconfigurable multifunctional device in two
dimensional WSe2.
AB - The three pillars of semiconductor device technologies are (1) the p-n diode, (2)
the metal-oxide-semiconductor field-effect transistor and (3) the bipolar
junction transistor. They have enabled the unprecedented growth in the field of
information technology that we see today. Until recently, the technological
revolution for better, faster and more efficient devices has been governed by
scaling down the device dimensions following Moore's Law. With the slowing of
Moore's law, there is a need for alternative materials and computing technologies
that can continue the advancement in functionality. Here, we describe a single,
dynamically reconfigurable device that implements these three fundamental device
functions. The device uses buried gates to achieve n- and p-channels and fits
into a larger effort to develop devices with enhanced functionalities, including
logic functions, over device scaling. As they are all surface conducting devices,
we use one material parameter, the interface trap density of states, to describe
the key figure-of-merit of each device.
PMID- 28510535
TI - Ultrafast magnetization dynamics in Nickel: impact of pump photon energy.
AB - Magnetization dynamics on a femtosecond timescale has been observed for a huge
variety of magnetic structures. However, the influence of different excitation
photon energies has not been studied in detail yet. In our time-resolved magneto
optical Kerr effect setup we excite a Nickel bulk system with 1.55 and 3.1 eV,
respectively, leading to different remagnetization dynamics depending on the
chosen photon energy. Furthermore we complement our experimental data with a
theoretical approach applying appropriate Boltzmann collision integrals including
the density of states of Nickel. The comparison between the experimental data and
the theoretical approach indicates that photon-energy dependent transport
processes play a major role in this setup.
PMID- 28510536
TI - Effect of nanostructures orientation on electroosmotic flow in a microfluidic
channel.
AB - Electroosmotic flow (EOF) is an electric-field-induced fluid flow that has
numerous micro-/nanofluidic applications, ranging from pumping to chemical and
biomedical analyses. Nanoscale networks/structures are often integrated in
microchannels for a broad range of applications, such as electrophoretic
separation of biomolecules, high reaction efficiency catalytic microreactors, and
enhancement of heat transfer and sensing. Their introduction has been known to
reduce EOF. Hitherto, a proper study on the effect of nanostructures orientation
on EOF in a microfluidic channel is yet to be carried out. In this investigation,
we present a novel fabrication method for nanostructure designs that possess
maximum orientation difference, i.e. parallel versus perpendicular indented
nanolines, to examine the effect of nanostructures orientation on EOF. It
consists of four phases: fabrication of silicon master, creation of mold insert
via electroplating, injection molding with cyclic olefin copolymer, and thermal
bonding and integration of practical inlet/outlet ports. The effect of
nanostructures orientation on EOF was studied experimentally by current
monitoring method. The experimental results show that nanolines which are
perpendicular to the microchannel reduce the EOF velocity significantly
(approximately 20%). This flow velocity reduction is due to the distortion of
local electric field by the perpendicular nanolines at the nanostructured surface
as demonstrated by finite element simulation. In contrast, nanolines which are
parallel to the microchannel have no effect on EOF, as it can be deduced that the
parallel nanolines do not distort the local electric field. The outcomes of this
investigation contribute to the precise control of EOF in lab-on-chip devices,
and fundamental understanding of EOF in devices which utilize nanostructured
surfaces for chemical and biological analyses.
PMID- 28510537
TI - Converging evolution leads to near maximal junction diversity through parallel
mechanisms in B and T cell receptors.
AB - T and B cell receptor (TCR and BCR) complementarity determining region 3 (CDR3)
genetic diversity is produced through multiple diversification and selection
stages. Potential holes in the CDR3 repertoire were argued to be linked to
immunodeficiencies and diseases. In contrast with BCRs, TCRs have practically no
Dbeta germline genetic diversity, and the question emerges as to whether they can
produce a diverse CDR3 repertoire. In order to address the genetic diversity of
the adaptive immune system, appropriate quantitative measures for diversity and
large-scale sequencing are required. Such a diversity method should incorporate
the complex diversification mechanisms of the adaptive immune response and the
BCR and TCR loci structure. We combined large-scale sequencing and diversity
measures to show that TCRs have a near maximal CDR3 genetic diversity.
Specifically, TCR have a larger junctional and V germline diversity, which starts
more 5' in Vbeta than BCRs. Selection decreases the TCR repertoire diversity, but
does not affect BCR repertoire. As a result, TCR is as diverse as BCR repertoire,
with a biased CDR3 length toward short TCRs and long BCRs. These differences
suggest parallel converging evolutionary tracks to reach the required diversity
to avoid holes in the CDR3 repertoire.
PMID- 28510538
TI - Measuring and assessing individual external doses during the rehabilitation phase
in Iitate village after the Fukushima Daiichi nuclear power plant accident.
AB - After the Fukushima Daiichi nuclear power plant accident in 2011, Iitate village
was placed under an evacuation order because the level of radioactive materials
drifting from the nuclear plant to the village was above a government-set level
for allowing residents to live in the area. The evacuation advisory for most of
the village was lifted on 31 March 2017. For displaced residents deciding whether
or not to return to their homes, it is important to correctly understand and
estimate the realistic individual external doses they will receive after
returning to the village. In this study, with the support of residents of the
village, we used a personal dosimeter (D-Shuttle) coupled with a global
positioning system device to measure and thus understand realistic individual
external doses while the residents were in Iitate village and to project the
individual external doses for different administrative districts as of 1 April
2017. The measured individual external doses measured by D-Shuttle for 38 study
participants showed that the doses measured during time spent inside the village
were higher and more widely distributed than the doses measured during time spent
outside the village. The exposure ratio (ER) was defined as the ratio of
additional individual external dose measured by D-Shuttle to the additional
ambient dose based on an airborne monitoring survey. The medians of the average
ERs were 0.13 (min-max 0.06-0.27) for time spent at home and 0.18 (min-max 0.08
0.36) for time spent outdoors. Projected additional annual individual external
doses as of 1 April 2017 for different administrative districts in the village
were calculated using ERs obtained in this study. Assuming that individuals spent
8 h per day on outdoor activities and 16 h on indoor activities, additional
annual individual external doses were estimated to be below 3 mSv using the mean
of the average ERs for most districts in the village, and these values were well
below the individual external doses estimated using the approach taken by the
central government. The results of this study provide valuable information both
for understanding realistic radiological situations in the village and for those
who want to know their future individual external dose in order to make a
decision on whether or not to live in the village.
PMID- 28510539
TI - Statistical physics approaches to subnetwork dynamics in biochemical systems.
AB - We apply a Gaussian variational approximation to model reduction in large
biochemical networks of unary and binary reactions. We focus on a small subset of
variables (subnetwork) of interest, e.g. because they are accessible
experimentally, embedded in a larger network (bulk). The key goal is to write
dynamical equations reduced to the subnetwork but still retaining the effects of
the bulk. As a result, the subnetwork-reduced dynamics contains a memory term and
an extrinsic noise term with non-trivial temporal correlations. We first derive
expressions for this memory and noise in the linearized (Gaussian) dynamics and
then use a perturbative power expansion to obtain first order nonlinear
corrections. For the case of vanishing intrinsic noise, our description is
explicitly shown to be equivalent to projection methods up to quadratic terms,
but it is applicable also in the presence of stochastic fluctuations in the
original dynamics. An example from the epidermal growth factor receptor
signalling pathway is provided to probe the increased prediction accuracy and
computational efficiency of our method.
PMID- 28510541
TI - Quick Hits.
PMID- 28510542
TI - From Science to Knowledge to Hope.
PMID- 28510540
TI - Diagnosis of Congenital Coarctation of the Aorta and Accompany Malformations in
Infants by Multi-Detector Computed Tomography Angiography and Transthoracic
Echocardiography: A Chinese Clinical Study.
AB - BACKGROUND The purpose of this study was to evaluate the utility of multi
detector computed tomography (MDCT) angiography and transthoracic
echocardiography (TTE) in the diagnosis of congenital coarctation of the aorta
(CoA) and accompanying malformations in infants. MATERIAL AND METHODS From
January 2012 and December 2015, we enrolled 68 infants with clinically suspected
CoA who underwent MDCT angiography and TTE in our hospital. Surgical correction
was conducted to confirm the diagnostic accuracy of both examinations in all
patients. RESULTS In this study, the diagnosis of CoA was confirmed infants by
surgical results in 55 of 68 infants. The diagnostic accuracy, sensitivity, and
specificity of MDCT angiography were 95.6%, 96.4%, and 92.3%, respectively. The
diagnostic accuracy, sensitivity, and specificity of TTE were 88.2%, 90.9%, and
76.9%, respectively. There was no significant difference in diagnostic accuracy,
sensitivity, and specificity between MDCT angiography and TTE (chi2=2.473,
p>0.05, chi2=1.373, p>0.05 and chi2=1.182, p>0.05, respectively). In the
diagnosis of concomitant cardiac abnormalities with CoA, the 2 methods also play
different roles. CONCLUSIONS MDCT angiography and TTE play different roles in the
diagnosis of CoA and accompany malformations. MDCT angiography in the diagnosis
of the extra-cardiac vascular malformations is better than TTE, and TTE is
superior to MDCT angiography in diagnosing intracardiac malformation. Combined
MDCT angiography and TTE is a relatively valuable, reliable, and noninvasive
method in the diagnosis of CoA and accompany malformations in infants.
PMID- 28510543
TI - Missing Link.
PMID- 28510544
TI - Science without Walls.
PMID- 28510545
TI - Food Fright!
PMID- 28510546
TI - Polar Ice Squad.
PMID- 28510547
TI - Greenland's Vanished Vikings.
PMID- 28510548
TI - Revenge of the Super Lice.
PMID- 28510550
TI - Romance of the Vanished Past.
PMID- 28510549
TI - The Quantum Multiverse.
PMID- 28510551
TI - The Meaning of Lichen.
PMID- 28510553
TI - Space Age Firefighters.
PMID- 28510552
TI - Print, Wipe, Rewrite.
PMID- 28510554
TI - Knowledge Is Infrastructure.
PMID- 28510556
TI - Making AI More Human.
PMID- 28510555
TI - The iOS 11 To-Do List.
PMID- 28510557
TI - Letters.
PMID- 28510558
TI - Sounds Like Trouble.
PMID- 28510559
TI - Unlocking the Mystery of ALS.
PMID- 28510560
TI - 50, 100 &150 Years Ago.
PMID- 28510561
TI - The Messy Truth about Weight Loss.
PMID- 28510562
TI - Menstrual Cycle "on a Chip".
PMID- 28510563
TI - Probing for Parkinson's.
PMID- 28510564
TI - Robo Pizzaiolo.
PMID- 28510565
TI - Electric Renaissance.
PMID- 28510566
TI - Radiation Triage.
PMID- 28510567
TI - Recommended.
PMID- 28510568
TI - Swell or High Water.
PMID- 28510569
TI - Lost at Sea.
PMID- 28510570
TI - BAG-1 as a biomarker in early breast cancer prognosis: a systematic review with
meta-analyses.
AB - BACKGROUND: The co-chaperone protein Bcl-2-associated athanogene-1 (BAG-1) is
overexpressed in breast cancer and has been incorporated in the oncotype DX and
PAM50 breast cancer prognostic assays. Bcl-2-associated athanogene-1 exists as
multiple protein isoforms that interact with diverse partners, including
chaperones Hsc70/Hsp70, Ser/Thr kinase Raf-1 and Bcl-2, to promote cancer cell
survival. The BAG-1L isoform specifically binds to and increases the
transcriptional activity of oestrogen receptor in cells, and in some, but not all
studies, BAG-1 expression is predictive of clinical outcome in breast cancer.
METHODS: A systematic review of published studies reporting BAG-1 (mRNA and/or
protein) expression and clinical outcome in early breast cancer. The REporting
Recommendations for Tumour MARKer and Prognostic Studies (REMARK) criteria were
used as a template against which data were assessed. Meta-analyses were performed
for studies that provided a hazard ratio and 95% confidence intervals for
clinical outcomes including disease-free survival or breast cancer-specific
survival from univariate analysis. RESULTS: Eighteen studies used differing
methodologies and reported on differing outcomes. Meta-analyses were only
possible on results from a subset of reported studies. Meta-analyses suggested
improved outcome with high BAG-1 mRNA and high BAG-1 nuclear expression by
immunohistochemisty. CONCLUSIONS: Increased levels of BAG-1 are associated with
better breast cancer outcomes.
PMID- 28510572
TI - 1.2 million kids and counting-Mobile science laboratories drive student interest
in STEM.
AB - In today's increasingly technological society, a workforce proficient in science,
technology, engineering, and mathematics (STEM) skills is essential. Research has
shown that active engagement by K-12 students in hands-on science activities that
use authentic science tools promotes student learning and retention. Mobile
laboratory programs provide this type of learning in schools and communities
across the United States and internationally. Many programs are members of the
Mobile Lab Coalition (MLC), a nonprofit organization of mobile and other
laboratory-based education programs built on scientist and educator
collaborations. A recent survey of the member programs revealed that they provide
an impressive variety of programming and have collectively served over 1.2
million students across the US.
PMID- 28510571
TI - Second-line pazopanib in patients with relapsed and refractory small-cell lung
cancer: a multicentre phase II study of the Hellenic Oncology Research Group.
AB - BACKGROUND: Pazopanib is a tyrosine kinase inhibitor with antiangiogenic
activity. Vascular endothelial growth factor expression is increased in SCLC and
is correlated with poor prognosis. The efficacy and tolerance of second-line
pazopanib in SCLC was evaluated. PATIENTS AND METHODS: Patients with platinum
sensitive (cohort A; n=39) and -resistant/refractory (cohort B; n=19) SCLC were
enrolled in a multicentre phase II study. The primary end point was the
progression-free survival rate (PFS-R) at week 8 in each cohort. Pazopanib (800
mg per day per os) was administered until progressive disease (PD). Circulating
tumour cells (CTCs) were enumerated using the Cellsearch assay. RESULTS: All
patients were evaluable for response and toxicity. In the intention-to-treat
analysis, eight (13.8%) patients achieved partial response (PR) (95% confidence
interval (CI): 5.0-22.7), 20 (34.5%) stable disease (SD) and 30 (51.7%) PD.
Accrual in cohort B was halted because the hard-stop rule was met; in cohort A,
the PFS-R was 59% (95% CI: 43.5-74.4; PR=7, SD=16). Nine (23.1%) patients
received pazopanib for >6 months and 3 of them for >12 months. One pazopanib
cycle resulted to a significant decrease to the number of patients with ?5
CTCs/7.5 ml of blood (20%) compared with baseline (50%). The median PFS and OS
for all patients was 2.5 months (95% CI: 1.9-3.1 months) and 6.0 months (95% CI:
3.8-8.2 months), respectively (cohort A: PFS=3.7 months and OS=8.0 months). No
unexpected toxicity was observed. CONCLUSIONS: Second-line treatment with
pazopanib in platinum-sensitive SCLC is well tolerated and resulted in promising
objective responses and disease control; CTC enumeration might serve as a
reliable surrogate biomarker of response.
PMID- 28510573
TI - Comparison of artemether-lumefantrine and chloroquine with and without primaquine
for the treatment of Plasmodium vivax infection in Ethiopia: A randomized
controlled trial.
AB - BACKGROUND: Recent efforts in malaria control have resulted in great gains in
reducing the burden of Plasmodium falciparum, but P. vivax has been more
refractory. Its ability to form dormant liver stages confounds control and
elimination efforts. To compare the efficacy and safety of primaquine regimens
for radical cure, we undertook a randomized controlled trial in Ethiopia. METHODS
AND FINDINGS: Patients with normal glucose-6-phosphate dehydrogenase status with
symptomatic P. vivax mono-infection were enrolled and randomly assigned to
receive either chloroquine (CQ) or artemether-lumefantrine (AL), alone or in
combination with 14 d of semi-supervised primaquine (PQ) (3.5 mg/kg total). A
total of 398 patients (n = 104 in the CQ arm, n = 100 in the AL arm, n = 102 in
the CQ+PQ arm, and n = 92 in the AL+PQ arm) were followed for 1 y, and recurrent
episodes were treated with the same treatment allocated at enrolment. The primary
endpoints were the risk of P. vivax recurrence at day 28 and at day 42. The risk
of recurrent P. vivax infection at day 28 was 4.0% (95% CI 1.5%-10.4%) after CQ
treatment and 0% (95% CI 0%-4.0%) after CQ+PQ. The corresponding risks were 12.0%
(95% CI 6.8%-20.6%) following AL alone and 2.3% (95% CI 0.6%-9.0%) following
AL+PQ. On day 42, the risk was 18.7% (95% CI 12.2%-28.0%) after CQ, 1.2% (95% CI
0.2%-8.0%) after CQ+PQ, 29.9% (95% CI 21.6%-40.5%) after AL, and 5.9% (95% CI
2.4%-13.5%) after AL+PQ (overall p < 0.001). In those not prescribed PQ, the risk
of recurrence by day 42 appeared greater following AL treatment than CQ treatment
(HR = 1.8 [95% CI 1.0-3.2]; p = 0.059). At the end of follow-up, the incidence
rate of P. vivax was 2.2 episodes/person-year for patients treated with CQ
compared to 0.4 for patients treated with CQ+PQ (rate ratio: 5.1 [95% CI 2.9
9.1]; p < 0.001) and 2.3 episodes/person-year for AL compared to 0.5 for AL+PQ
(rate ratio: 6.4 [95% CI 3.6-11.3]; p < 0.001). There was no difference in the
occurrence of adverse events between treatment arms. The main limitations of the
study were the early termination of the trial and the omission of haemoglobin
measurement after day 42, resulting in an inability to estimate the cumulative
risk of anaemia. CONCLUSIONS: Despite evidence of CQ-resistant P. vivax, the risk
of recurrence in this study was greater following treatment with AL unless it was
combined with a supervised course of PQ. PQ combined with either CQ or AL was
well tolerated and reduced recurrence of vivax malaria by 5-fold at 1 y. TRIAL
REGISTRATION: ClinicalTrials.gov NCT01680406.
PMID- 28510574
TI - Dose of antivenom for the treatment of snakebite with neurotoxic envenoming:
Evidence from a randomised controlled trial in Nepal.
AB - BACKGROUND: Currently, there is inadequate evidence on which to base clinical
management of neurotoxic snakebite envenoming, especially in the choice of
initial antivenom dosage. This randomised controlled trial compared the
effectiveness and safety of high versus low initial antivenom dosage in victims
of neurotoxic envenoming. METHODOLOGY/ PRINCIPAL FINDINGS: This was a balanced,
randomised, double-blind trial that was conducted in three health care centers
located in the Terai plains of Nepal. Participants received either low (two
vials) or high (10 vials) initial dosage of Indian polyvalent antivenom. The
primary composite outcome consisted of death, the need for assisted ventilation
and worsening/recurrence of neurotoxicity. Hourly evaluations followed antivenom
treatment. Between April 2011 and October 2012, 157 snakebite victims were
enrolled, of which 154 were analysed (76 in the low and 78 in the high initial
dose group). Sixty-seven (43.5%) participants met the primary outcome definition.
The proportions were similar in the low (37 or 48.7%) vs. high (30 or 38.5%)
initial dose group (difference = 10.2%, 95%CI [-6.7 to 27.1], p = 0.264). The
mean number of vials used was similar between treatment groups. Overall, patients
bitten by kraits did worse than those bitten by cobras. The occurrence of
treatment-related adverse events did not differ among treatment groups. A total
of 19 serious adverse events occurred, including seven attributed to antivenom.
CONCLUSIONS: This first robust trial investigating antivenom dosage for
neurotoxic snakebite envenoming shows that the antivenom currently used in Nepal
performs poorly. Although the high initial dose regimen is not more effective
than the low initial dose, it offers the practical advantage of being a single
dose, while not incurring higher consumption or enhanced risk of adverse
reaction. The development of new and more effective antivenoms that better target
the species responsible for bites in the region will help improve future
patients' outcomes. TRIAL REGISTRATION: The study was registered on
clinicaltrials.gov (NCT01284855) (GJ 5/1).
PMID- 28510575
TI - Electro-mechanical dynamics of spiral waves in a discrete 2D model of human
atrial tissue.
AB - We investigate the effect of mechano-electrical feedback and atrial fibrillation
induced electrical remodelling (AFER) of cellular ion channel properties on the
dynamics of spiral waves in a discrete 2D model of human atrial tissue. The
tissue electro-mechanics are modelled using the discrete element method (DEM).
Millions of bonded DEM particles form a network of coupled atrial cells
representing 2D cardiac tissue, allowing simulations of the dynamic behaviour of
electrical excitation waves and mechanical contraction in the tissue. In the
tissue model, each cell is modelled by nine particles, accounting for the
features of individual cellular geometry; and discrete inter-cellular spatial
arrangement of cells is also considered. The electro-mechanical model of a human
atrial single-cell was constructed by strongly coupling the electrophysiological
model of Colman et al. to the mechanical myofilament model of Rice et al., with
parameters modified based on experimental data. A stretch-activated channel was
incorporated into the model to simulate the mechano-electrical feedback. In order
to investigate the effect of mechano-electrical feedback on the dynamics of
spiral waves, simulations of spiral waves were conducted in both the
electromechanical model and the electrical-only model in normal and AFER
conditions, to allow direct comparison of the results between the models.
Dynamics of spiral waves were characterized by tracing their tip trajectories,
stability, excitation frequencies and meandering range of tip trajectories. It
was shown that the developed DEM method provides a stable and efficient model of
human atrial tissue with considerations of the intrinsically discrete and
anisotropic properties of the atrial tissue, which are challenges to handle in
traditional continuum mechanics models. This study provides mechanistic insights
into the complex behaviours of spiral waves and the genesis of atrial
fibrillation by showing an important role of the mechano-electrical feedback in
facilitating and promoting atrial fibrillation.
PMID- 28510576
TI - Comparison of peripapillary choroidal thickness between healthy subjects and
patients with Parkinson's disease.
AB - PURPOSE: To study peripapillary choroidal thickness (PPCT) in healthy subjects
using swept-source optical coherence tomography (SS-OCT), and to evaluate PPCT
differences between Parkinson's disease (PD) patients, and age- and sex-matched
healthy controls. DESIGN: Case-control study. METHODS: 80 healthy subjects and 40
PD patients were consecutively recruited in this single institution study. The
healthy subjects were divided into two populations: a teaching population (n =
40, used to establish choroidal zones) and a validating population (n = 40, used
to compare measurements with PD patients). An optic disc 6.0*6.0 mm three
dimensional scan was obtained using Deep Range Imaging (DRI) OCT Triton. A 26*26
cube-grid centered on the optic disc was generated to automatically measure
choroidal thickness. Five concentric choroidal zones were established and used to
compare PPCT between healthy and PD patients. RESULTS: PPCT was significantly
thicker in PD patients compared with controls in all four concentric zones
evaluated (p<=0.0001). PPCT followed a similar pattern in controls and PD; it was
thicker in the temporosuperior region, followed by the superior, temporal, nasal,
and inferior regions. CONCLUSION: PD patients presented with an increased PPCT in
all zones surrounding the optic disc compared with healthy subjects. The
peripapillary choroidal tissue showed a concentric pattern, with the thickness
increasing with increasing distance from the optic nerve. SS-OCT could be useful
for evaluating choroidal thinning in clinical practice.
PMID- 28510577
TI - Are horses capable of mirror self-recognition? A pilot study.
AB - Mirror Self-Recognition (MSR) unveils complex cognitive, social and emotional
skills and it has been found only in humans and few other species, such as great
apes, dolphins, elephants and magpies. In this pilot study, we tested if horses
show the capacity of MSR. Four subjects living socially under naturalistic
conditions were selected for the experiment. We adopted the classical mark test,
which consists in placing a coloured mark on an out-of-view body part, visible
only through mirror inspection. If the animal considers the image as its own, it
will use its reflection to detect the mark and will try to explore it. We
enhanced the classical paradigm by introducing a double-check control. Only in
the presence of the reflecting surface, animals performed tactile and olfactory
exploration of the mirror and looked behind it. These behaviors suggest that
subjects were trying to associate multiple sensory cues (visual, tactile and
olfactory) to the image in the mirror. The lack of correspondence between the
collected stimuli in front of the mirror and the response to the colored mark
lead us to affirm that horses are able to perceive that the reflected image is
incongruent when compared with the memorized information of a real horse.
However, without replication of data, the self-directed behavior towards the
colored marks showed by our horses cannot be sufficient per se to affirm that
horses are capable of self-recognition.
PMID- 28510578
TI - Neurofeedback as a form of cognitive rehabilitation therapy following stroke: A
systematic review.
AB - Neurofeedback therapy (NFT) has been used within a number of populations however
it has not been applied or thoroughly examined as a form of cognitive
rehabilitation within a stroke population. Objectives for this systematic review
included: i) identifying how NFT is utilized to treat cognitive deficits
following stroke, ii) examining the strength and quality of evidence to support
the use of NFT as a form of cognitive rehabilitation therapy (CRT) and iii)
providing recommendations for future investigations. Searches were conducted
using OVID (Medline, Health Star, Embase + Embase Classic) and PubMed databases.
Additional searches were completed using the Cochrane Reviews library database,
Google Scholar, the University of Toronto online library catalogue,
ClinicalTrials.gov website and select journals. Searches were completed Feb/March
2015 and updated in June/July/Aug 2015. Eight studies were eligible for inclusion
in this review. Studies were eligible for inclusion if they: i) were specific to
a stroke population, ii) delivered CRT via a NFT protocol, iii) included
participants who were affected by a cognitive deficit(s) following stroke (i.e.
memory loss, loss of executive function, speech impairment etc.). NFT protocols
were highly specific and varied within each study. The majority of studies
identified improvements in participant cognitive deficits following the
initiation of therapy. Reviewers assessed study quality using the Downs and Black
Checklist for Measuring Study Quality tool; limited study quality and strength of
evidence restricted generalizability of conclusions regarding the use of this
therapy to the greater stroke population. Progression in this field requires
further inquiry to strengthen methodology quality and study design. Future
investigations should aim to standardize NFT protocols in an effort to understand
the dose-response relationship between NFT and improvements in functional
outcome. Future investigations should also place a large emphasis on long-term
participant follow-up.
PMID- 28510582
TI - The worst case scenario: Locomotor and collision demands of the longest periods
of gameplay in professional rugby union.
AB - A number of studies have used global positioning systems (GPS) to report on
positional differences in the physical game demands of rugby union both on an
average and singular bout basis. However, the ability of these studies to report
quantitative data is limited by a lack of validation of certain aspects of
measurement by GPS micro-technology. Furthermore no study has analyzed the
positional physical demands of the longest bouts of ball-in-play time in rugby
union. The aim of the present study is to compare the demands of the single
longest period of ball-in-play, termed "worst case scenario" (WCS) between
positional groups, which have previously been reported to have distinguishable
game demands. The results of this study indicate that WCS periods follow a
similar sporadic pattern as average demands but are played at a far higher pace
than previously reported for average game demands with average meters per minute
of 116.8 m. The positional differences in running and collision activity
previously reported are perpetuated within WCS periods. Backs covered greater
total distances than forwards (318 m vs 289 m), carried out more high-speed
running (11.1 m.min-1 vs 5.5 m.min-1) and achieved higher maximum velocities
(MaxVel). Outside Backs achieved the highest MaxVel values (6.84 m.sec-1). Tight
Five and Back Row forwards underwent significantly more collisions than Inside
Back and Outside Backs (0.73 & 0.89 collisions.min-1 vs 0.28 & 0.41
collisions.min-1 respectively). The results of the present study provide
information on the positional physical requirements of performance in prolonged
periods involving multiple high intensity bursts of effort. Although the current
state of GPS micro-technology as a measurement tool does not permit reporting of
collision intensity or acceleration data, the combined use of video and GPS
provides valuable information to the practitioner. This can be used to match and
replicate game demands in training.
PMID- 28510579
TI - Socio-economic status over the life course and obesity: Systematic review and
meta-analysis.
AB - BACKGROUND: The purpose of this review was to summarize the published literature
on the association of childhood, adulthood and life course socio-economic status
(SES) with obesity between January 1990 and June 2015. METHODS: The major medical
electronic databases were searched to identify studies that examined SES over the
life-course in relation to obesity. A total of 219 studies were identified
through the initial search, and 35 qualified for full review. Of these, 14
publications met our inclusion criteria for the meta-analysis, all from developed
or upper-middle income countries. RESULTS: There was a consistent association
between lower life course SES and obesity among women (summary OR: 1.35, 95% CI:
1.04, 1.76), but not among men (summary OR: 0.92, 95% CI: 0.60, 1.40). Overall,
mean BMI was higher among individuals with lower life course SES compared with
those with higher life course SES (summary mean BMI difference: 0.65, 95% CI:
0.59, 0.71). Mean waist circumference (WC) was higher among women with lower life
course SES compared with those with higher life course SES (summary mean WC:
4.67, 95% CI: 4.15, 5.20), but lower among men (summary mean WC difference:
0.10, 95% CI: -0.11, -0.08). CONCLUSION: The inverse relationship between life
course SES and obesity among women was consistent, based mostly on studies in
developed countries. Nevertheless, critical information gaps remain in relation
to the impact of childhood and life course SES on obesity in developing
countries.
PMID- 28510580
TI - Disease-associated mitochondrial mutations and the evolution of primate
mitogenomes.
AB - Several human diseases have been associated with mutations in mitochondrial genes
comprising a set of confirmed and reported mutations according to the MITOMAP
database. An analysis of complete mitogenomes across 139 primate species showed
that most confirmed disease-associated mutations occurred in aligned codon
positions and gene regions under strong purifying selection resulting in a strong
evolutionary conservation. Only two confirmed variants (7.1%), coding for the
same amino acids accounting for severe human diseases, were identified without
apparent pathogenicity in non-human primates, like the closely related Bornean
orangutan. Conversely, reported disease-associated mutations were not especially
concentrated in conserved codon positions, and a large fraction of them occurred
in highly variable ones. Additionally, 88 (45.8%) of reported mutations showed
similar variants in several non-human primates and some of them have been present
in extinct species of the genus Homo. Considering that recurrent mutations
leading to persistent variants throughout the evolutionary diversification of
primates are less likely to be severely damaging to fitness, we suggest that
these 88 mutations are less likely to be pathogenic. Conversely, 69 (35.9%) of
reported disease-associated mutations occurred in extremely conserved aligned
codon positions which makes them more likely to damage the primate mitochondrial
physiology.
PMID- 28510583
TI - Liver fibrosis staging with a new 2D-shear wave elastography using comb-push
technique: Applicability, reproducibility, and diagnostic performance.
AB - OBJECTIVE: To evaluate the applicability, reproducibility, and diagnostic
performance of a new 2D-shear wave elastography (SWE) using the comb-push
technique (2D CP-SWE) for detection of hepatic fibrosis, using histopathology as
the reference standard. MATERIALS AND METHODS: This prospective study was
approved by the institutional review board, and informed consent was obtained
from all patients. The liver stiffness (LS) measurements were obtained from 140
patients, using the new 2D-SWE, which uses comb-push excitation to produce shear
waves and a time-aligned sequential tracking method to detect shear wave signals.
The applicability rate of 2D CP-SWE was estimated, and factors associated with
its applicability were identified. Intraobserver reproducibility was evaluated in
the 105 patients with histopathologic diagnosis, and interobserver
reproducibility was assessed in 20 patients. Diagnostic performance of the 2D CP
SWE for hepatic fibrosis was evaluated by receiver operating characteristic (ROC)
curve analysis. RESULTS: The applicability rate of 2D CP-SWE was 90.8% (109 of
120). There was a significant difference in age, presence or absence of ascites,
and the distance from the transducer to the Glisson capsule between the patients
with applicable LS measurements and patients with unreliable measurement or
technical failure. The intraclass correlation of interobserver agreement was
0.87, and the value for the intraobserver agreement was 0.95. The area under the
ROC curve of LS values for stage F2 fibrosis or greater, stage F3 or greater, and
stage F4 fibrosis was 0.874 (95% confidence interval [CI]: 0.794-0.930), 0.905
(95% CI: 0.832-0.954), and 0.894 (95% CI: 0.819-0.946), respectively. CONCLUSION:
2D CP-SWE can be employed as a reliable method for assessing hepatic fibrosis
with a reasonably good diagnostic performance, and its applicability might be
influenced by age, ascites, and the distance between the transducer and Glisson
capsule.
PMID- 28510581
TI - Association between the hyperuricemia and nonalcoholic fatty liver disease risk
in a Chinese population: A retrospective cohort study.
AB - Nonalcoholic fatty liver disease (NAFLD) is a common chronic disease associated
with high levels of serum uric acid (SUA). However, whether this relationship
applies in obese subjects has been unclear, and no cohort study has previously
been conducted in non-obese subjects. We therefore performed a retrospective
cohort study among employees of seven companies in China to investigate whether
hyperuricemia was independently associated with NAFLD in obese and non-obese
subjects, respectively. A total of 2383 initially NAFLD-free subjects were
followed up for four years, and 15.2% (363/2383) developed NAFLD. Hyperuricemia
subjects had a higher cumulative incidence than did those with normouricemia
(29.0% vs. 12.9%, P<0.001). Cox proportional hazard regression analyses showed
that baseline hyperuricemia was significantly associated with risk of developing
NAFLD in non-obese subjects. This relationship was significantly independent of
baseline age, gender, metabolic syndrome components, and other clinical variables
(RR = 1.389, 95%CI: 1.051-2.099). However, this association did not exist in
obese subjects (RR = 1.010, 95%CI: 0.649-1.571). The independent effect of
hyperuricemia on NAFLD was stronger in females (RR = 2.138, 95%CI: 1.050-4.355)
than in males (RR = 1.435, 95%CI: 1.021-2.018). In conclusion, further studies
are needed to explore the different mechanisms between obese and non-obese
subjects, and the reason hyperuricemia raises NAFLD risk in females more than in
males.
PMID- 28510584
TI - Identification of novel risk factors for community-acquired Clostridium difficile
infection using spatial statistics and geographic information system analyses.
AB - BACKGROUND: The rate of community-acquired Clostridium difficile infection (CA
CDI) is increasing. While receipt of antibiotics remains an important risk factor
for CDI, studies related to acquisition of C. difficile outside of hospitals are
lacking. As a result, risk factors for exposure to C. difficile in community
settings have been inadequately studied. MAIN OBJECTIVE: To identify novel
environmental risk factors for CA-CDI. METHODS: We performed a population-based
retrospective cohort study of patients with CA-CDI from 1/1/2007 through
12/31/2014 in a 10-county area in central North Carolina. 360 Census Tracts in
these 10 counties were used as the demographic Geographic Information System
(GIS) base-map. Longitude and latitude (X, Y) coordinates were generated from
patient home addresses and overlaid to Census Tracts polygons using ArcGIS;
ArcView was used to assess "hot-spots" or clusters of CA-CDI. We then constructed
a mixed hierarchical model to identify environmental variables independently
associated with increased rates of CA-CDI. RESULTS: A total of 1,895 unique
patients met our criteria for CA-CDI. The mean patient age was 54.5 years; 62%
were female and 70% were Caucasian. 402 (21%) patient addresses were located in
"hot spots" or clusters of CA-CDI (p<0.001). "Hot spot" census tracts were
scattered throughout the 10 counties. After adjusting for clustering and
population density, age >= 60 years (p = 0.03), race (<0.001), proximity to a
livestock farm (0.01), proximity to farming raw materials services (0.02), and
proximity to a nursing home (0.04) were independently associated with increased
rates of CA-CDI. CONCLUSIONS: Our study is the first to use spatial statistics
and mixed models to identify important environmental risk factors for acquisition
of C. difficile and adds to the growing evidence that farm practices may put
patients at risk for important drug-resistant infections.
PMID- 28510585
TI - The prevalence of underweight, overweight and obesity in Bangladeshi adults: Data
from a national survey.
AB - BACKGROUND: Over the two last decades Bangladesh, a low-income country, has
experienced a rapid demographic and epidemiological transition. The population
has increased substantially with rapid urbanization and changing pattern of
disease, which at least in part, can be explained by nutritional changes.
However, the nutritional status of the adult population has not been previously
described. Hence, the objective of this study was to estimate the prevalence and
explore socio-demographic determinants of underweight, overweight and obesity
among the Bangladeshi adult population. METHODS: This study is a secondary data
analysis of the national 2011 Bangladesh Demographic and Health Survey. We
determined the nutritional status of adults aged >=35 years of age, who had a
measured weight and height, using the Asian body mass index (BMI) cut-offs for
underweight (BMI <18.5 kg/m2), overweight (BMI 23 to <27.5 kg/m2) and obesity
(BMI >=27.5 kg/m2). Logistic regression modeling was used to determine the
association between socio-demographic factors and nutritional status. RESULT: Of
total sample (n = 5495), 30.4% were underweight, 18.9% were overweight and 4.6%
were obese. Underweight was associated with age, education and wealth. The
adjusted odd ratios for underweight were higher for older people (>=70 years)
compared to younger, the least educated compared to the most educated and the
poorest compared to the wealthiest were 2.51 (95%CI: 1.95-3.23, p<0.001), 3.59
(95%CI: 2.30-5.61, p<0.001) and 3.70 (95%CI: 2.76-4.96, p<0.001), respectively.
Younger age (35-44 years), being female, higher education, wealthier and living
in urban areas were associated with overweight/obesity with adjusted odds ratios
of 1.73 (95%CI: 1.24-2.41, p<0.001), 2.48 (95%CI: 1.87-3.28, p<0.001), 3.98
(95%CI: 2.96-5.33, p<0.001), 7.14 (95%CI: 5.20-9.81, p<0.001) 1.27 (95%CI: 1.05
1.55, p-0.02), respectively. CONCLUSION: Underweight and overweight/obesity are
prevalent in Bangladeshi adults. Both conditions are associated with increased
morbidity and mortality and increase the risk of developing non-communicable
diseases. Effective public health intervention approaches are necessary to
address both these conditions.
PMID- 28510586
TI - Truncation of the TAR DNA-binding protein 43 is not a prerequisite for
cytoplasmic relocalization, and is suppressed by caspase inhibition and by
introduction of the A90V sequence variant.
AB - The RNA-binding and -processing protein TAR DNA-binding protein 43 (TDP-43) is
heavily linked to the underlying causes and pathology of neurodegenerative
diseases such as amyotrophic lateral sclerosis and frontotemporal lobar
degeneration. In these diseases, TDP-43 is mislocalized, hyperphosphorylated,
ubiquitinated, aggregated and cleaved. The importance of TDP-43 cleavage in the
disease pathogenesis is still poorly understood. Here we detail the use of D
sorbitol as an exogenous stressor that causes TDP-43 cleavage in HeLa cells,
resulting in a 35 kDa truncated product that accumulates in the cytoplasm within
one hour of treatment. We confirm that the formation of this 35 kDa cleavage
product is mediated by the activation of caspases. Inhibition of caspases blocks
the cleavage of TDP-43, but does not prevent the accumulation of full-length
protein in the cytoplasm. Using D-sorbitol as a stressor and caspase activator,
we also demonstrate that the A90V variant of TDP-43, which lies adjacent to the
caspase cleavage site within the nuclear localization sequence of TDP-43, confers
partial resistance against caspase-mediated generation of the 35 kDa cleavage
product.
PMID- 28510587
TI - Sibling method increases risk assessment estimates for type 1 diabetes.
AB - We presented a risk assessment model to distinguish between type 1 diabetes (T1D)
affected and unaffected siblings using only three single nucleotide polymorphism
(SNP) genotypes. In addition we calculated the heritability from genome-wide
identity-by-descent (IBD) sharing between full siblings. We analyzed 1,253 pairs
of affected individuals and their unaffected siblings (750 pairs from a discovery
set and 503 pairs from a validation set) from the T1D Genetics Consortium
(T1DGC), applying a logistic regression to analyze the area under the receiver
operator characteristic (ROC) curve (AUC). To calculate the heritability of T1D
we used the Haseman-Elston regression analysis of the squared difference between
the phenotypes of the pairs of siblings on the estimate of their genome-wide IBD
proportion. The model with only 3 SNPs achieving an AUC of 0.75 in both datasets
outperformed the model using the presence of the high-risk DR3/4 HLA genotype,
namely AUC of 0.60. The heritability on the liability scale of T1D was
approximately from 0.53 to 0.92, close to the results obtained from twin studies,
ranging from 0.4 to 0.88.
PMID- 28510590
TI - Community-based human-elephant conflict mitigation: The value of an evidence
based approach in promoting the uptake of effective methods.
AB - Human-elephant conflict (HEC) is a serious threat to elephants and can cause
major economic losses. It is widely accepted that reduction of HEC will often
require community-based methods for repelling elephants but there are few tests
of such methods. We tested community-based crop-guarding methods with and without
novel chili-based elephant deterrents and describe changes in farmers'
willingness to adopt these methods following our demonstration of their relative
effectiveness. In three separate field-trials that took place over almost two
years (October 2005 -May 2007) in two villages adjacent to Way Kambas National
Park (WKNP) in Indonesia, we found that community-based crop-guarding was
effective at keeping Asian elephants (Elephas maximus) out of crop fields in
91.2% (52 out of 57), 87.6% (156 out of 178), and 80.0% (16 out of 20) of
attempted raids. Once the method had been shown to be effective at demonstration
sites, farmers in 16 villages around WKNP voluntarily adopted it during the July
2008 to March 2009 period and were able to repel elephants in 73.9% (150 out of
203) of attempted raids, with seven villages repelling 100% of attempted raids.
These 16 villages had all experienced high levels of HEC in the preceding years;
e.g. they accounted for >97% of the 742 HEC incidents recorded for the entire
park in 2006. Our work shows, therefore, that a simple evidence-based approach
can facilitate significant reductions in HEC at the protected area scale.
PMID- 28510588
TI - Evolutionary restoration of fertility in an interspecies hybrid yeast, by whole
genome duplication after a failed mating-type switch.
AB - Many interspecies hybrids have been discovered in yeasts, but most of these
hybrids are asexual and can replicate only mitotically. Whole-genome duplication
has been proposed as a mechanism by which interspecies hybrids can regain
fertility, restoring their ability to perform meiosis and sporulate. Here, we
show that this process occurred naturally during the evolution of
Zygosaccharomyces parabailii, an interspecies hybrid that was formed by mating
between 2 parents that differed by 7% in genome sequence and by many
interchromosomal rearrangements. Surprisingly, Z. parabailii has a full sexual
cycle and is genetically haploid. It goes through mating-type switching and
autodiploidization, followed by immediate sporulation. We identified the key
evolutionary event that enabled Z. parabailii to regain fertility, which was
breakage of 1 of the 2 homeologous copies of the mating-type (MAT) locus in the
hybrid, resulting in a chromosomal rearrangement and irreparable damage to 1 MAT
locus. This rearrangement was caused by HO endonuclease, which normally functions
in mating-type switching. With 1 copy of MAT inactivated, the interspecies hybrid
now behaves as a haploid. Our results provide the first demonstration that MAT
locus damage is a naturally occurring evolutionary mechanism for whole-genome
duplication and restoration of fertility to interspecies hybrids. The events that
occurred in Z. parabailii strongly resemble those postulated to have caused
ancient whole-genome duplication in an ancestor of Saccharomyces cerevisiae.
PMID- 28510591
TI - The case for investing in the male condom.
AB - When used correctly and consistently, the male condom offers triple protection
from unintended pregnancy and the transmission of sexually transmitted infections
(STIs) and human immunodeficiency virus (HIV). However, with health funding
levels stagnant or falling, it is important to understand the cost and health
impact associated with prevention technologies. This study is one of the first to
attempt to quantify the cost and combined health impact of condom use, as a means
to prevent unwanted pregnancy and to prevent transmission of STIs including HIV.
This paper describes the analysis to make the case for investment in the male
condom, including the cost, impact and cost-effectiveness by three scenarios (low
in which 2015 condom use levels are maintained; medium in which condom use trends
are used to predict condom use from 2016-2030; and high in which condom use is
scaled up, as part of a package of contraceptives, to meet all unmet need for
family planning by 2030 and to 90% for HIV and STI prevention by 2016) for 81
countries from 2015-2030. An annual gap between current and desired use of 10.9
billion condoms was identified (4.6 billion for family planning and 6.3 billion
for HIV and STIs). Under a high scenario that completely reduces that gap between
current and desired use of 10.9 billion condoms, we found that by 2030 countries
could avert 240 million DALYs. The additional cost in the 81 countries through
2030 under the medium scenario is $1.9 billion, and $27.5 billion under the high
scenario. Through 2030, the cost-effectiveness ratios are $304 per DALY averted
for the medium and $115 per DALY averted for the high scenario. Under the three
scenarios described above, our analysis demonstrates the cost-effectiveness of
the male condom in preventing unintended pregnancy and HIV and STI new
infections. Policy makers should increase budgets for condom programming to
increase the health return on investment of scarce resources.
PMID- 28510589
TI - Establishment of a combination scoring method for diagnosis of ocular adnexal
lymphoproliferative disease.
AB - Lymphoproliferative diseases (LPDs) of the ocular adnexa encompass the majority
of orbital diseases and include reactive follicular hyperplasia (RFH), atypical
lymphoid hyperplasia (ALH), and mucosa-associated lymphoid tissue lymphoma
(MALToma). Lymphoid follicles (LFs) are usually observed during the histological
examination of LPDs. Currently, because there is a lack of specific clinical
signs and diagnostic immunohistochemical biomarkers, it is difficult for
pathologists to distinguish MALToma from ocular RFH and ALH, which makes the
clinical management of these conditions difficult. Here, we analyzed the clinical
features of patients with ocular adnexal LPDs (n = 125) and investigated the
structure of LFs in paraffin-embedded tissue samples using anti-CD23 and anti-IgD
immunochemistry. We found that some clinical features including age, sex, and
laterality were different among RFH, LFH, and MALToma. Additionally,
immunohistochemistry revealed that the expression of IgD and CD23 was higher in
RFH patients and decreased in patients with ALH and MALToma. Moreover, LFs in RFH
were intact, whereas the structures of most LFs were disrupted in ALH. In MALToma
specimens, few intact LFs were observed. In a further investigation, we combined
the results for CD23/IgD immunohistochemistry and the structure of LFs to
establish a scoring method for the differential diagnosis of LPDs. According to
the BIOMED-2 protocol, we further detected IgH gene monoclonal rearrangement in
73 cases (35 RFH, 17 ALH, and 21 MALToma cases). The sensitivity of our scoring
method, based on a comparison with the results of IgH gene monoclonal
rearrangement detection, was 85.7% (18/21) for MALToma and 35.3% (6/17) for ALH.
Our study provides a method that may be useful for the differential diagnosis of
RFH, ALH, and MALToma.
PMID- 28510592
TI - Alteration of protein function by a silent polymorphism linked to tRNA abundance.
AB - Synonymous single nucleotide polymorphisms (sSNPs) are considered neutral for
protein function, as by definition they exchange only codons, not amino acids. We
identified an sSNP that modifies the local translation speed of the cystic
fibrosis transmembrane conductance regulator (CFTR), leading to detrimental
changes to protein stability and function. This sSNP introduces a codon pairing
to a low-abundance tRNA that is particularly rare in human bronchial epithelia,
but not in other human tissues, suggesting tissue-specific effects of this sSNP.
Up-regulation of the tRNA cognate to the mutated codon counteracts the effects of
the sSNP and rescues protein conformation and function. Our results highlight the
wide-ranging impact of sSNPs, which invert the programmed local speed of mRNA
translation and provide direct evidence for the central role of cellular tRNA
levels in mediating the actions of sSNPs in a tissue-specific manner.
PMID- 28510593
TI - No serological evidence for Zika virus infection and low specificity for anti
Zika virus ELISA in malaria positive individuals among pregnant women from
Madagascar in 2010.
AB - It was previously reported that a malaria infection may interfere with the
specificity of a commercial ELISA test against Zika virus (ZIKV). We analyzed
1,216 plasma samples from healthy, pregnant women collected in two sites in
Madagascar in 2010 for ZIKV antibodies using a commercial ELISA and for
Plasmodium infection by PCR. This screen revealed six putative ZIKV-positive
samples by ELISA. These results could not be confirmed by indirect
immunofluorescence assays or virus neutralization tests. Four of these six
samples were also positive for P. falciparum. We noted that the frequency of
malaria positivity was higher in ZIKV-ELISA positive samples (50% and 100% in the
two study sites) than ZIKV-negative samples (17% and 10%, respectively),
suggesting that malaria may have led to false ZIKV-ELISA positives.
PMID- 28510596
TI - Utilization of growth monitoring and promotion services and associated factors
among under two years of age children in Southern Ethiopia.
AB - Growth monitoring and promotion (GMP) is a prevention activity comprised of
growth monitoring (GM) linked with promotion that serves as the core activity in
an integrated child health and nutrition program. However, different methods of
institutional studies have shown that utilization of GM services has remained to
be inadequate. There is scarcity of studies conducted about GMP in quantitative
method. Therefore, this study was conducted to address the proportion of GMP
services and associated factors among children under two years of age in rural
communities of Mareka district, Southern Ethiopia. Community based cross
sectional survey was conducted from August to September 2015. Single population
proportion formula was used to determine the sample size with multi stage
sampling technique. A total of 819 children under two years of age were included.
Pretest was done on 10% of the total sample size. Data were analyzed using SPSS
version 20.0 software. Bivariate and multivariate logistic regressions used to
analyze data. The response rate was 95%. Utilization of GMP services was 16.9%.
Institutional delivery AOR (95% CI): 3.01(1.65-5.50), index child age 12-17
months AOR (95% CI): 4.03(2.16-7.51) and 18-23 months AOR (95% CI): 3.08(1.70
5.57), family size 4-5 AOR(95% CI): 0.14(0.06-0.33), family size >5 AOR(95% CI):
0.34(0.14-0.82), regular GMP attendance AOR (95% CI): 4.37(2.45-7.80), medium
wealth index AOR(95% CI): 3.14(1.51-6.52) and high wealth index AOR(95% CI):
3.24(1.59-6.62) were factors associated with utilization of GMP services.
Utilization of GMP services was low. Thus, efforts should be made to improve
utilization of GMP services through promotion of institutional delivery,
different family planning methods, and regular GMP attendance.
PMID- 28510594
TI - Long term type 1 diabetes is associated with hand pain, disability and stiffness
but not with structural hand osteoarthritis features - The Dialong hand study.
AB - OBJECTIVE: To explore whether having long-term type 1 diabetes (>45 years) is
associated with a higher prevalence of radiographic hand OA, erosive hand OA and
increased hand pain, disability and stiffness. METHODS: In total N = 96 persons
with type 1 diabetes diagnosed before 1970 were included (mean [SD] age: 62.2
[7.4], mean [SD] HbA1c: 7.43 [0.80] and N = 49 [51%] men). Regular measurements
of their HbA1c were obtained till 2015. We included N = 69 healthy controls
without any diabetes (mean [SD] age: 63.0 [7.0], mean [SD] HbA1c: 5.41 [0.32], N
= 29 [42%] men). The groups were compared for radiographic hand OA (Kellgren
Lawrence grade >=2 in >=1 joint) and erosive hand OA (central erosions in >=1
joint), Australian/Canadian index (AUSCAN) for hand pain, disability and
stiffness using regression analyses adjusted for age, sex, educational level and
waist circumference. RESULTS: We found no associations between having long term
type 1 diabetes and more prevalent radiographic hand OA (OR = 0.83, 95% CI = 0.38
1.81). We found a trend towards higher prevalence of erosive hand OA in diabetes
patients (OR = 2.96, 95% CI = 0.82-10.64). Strong and consistent associations
were observed between long term type 1 diabetes and increased hand pain (B =
2.78, 95% CI = 1.65-3.91), disability (B = 5.30, 95% CI = 3.48-7.12) and
stiffness (B = 2.00, 95% CI = 1.33-2.67). These associations were particularly
strong for women and participants below the median age of 61 years. CONCLUSION:
Long-term type 1 diabetes was not associated with radiographic hand OA, but was
strongly associated with hand pain, disability and stiffness. The association
between diabetes and erosive hand OA warrants further investigation.
PMID- 28510595
TI - Structural adaptations of octaheme nitrite reductases from haloalkaliphilic
Thioalkalivibrio bacteria to alkaline pH and high salinity.
AB - Bacteria Tv. nitratireducens and Tv. paradoxus from soda lakes grow optimally in
sodium carbonate/NaCl brines at pH range from 9.5 to 10 and salinity from 0.5 to
1.5 M Na+. Octaheme nitrite reductases (ONRs) from haloalkaliphilic bacteria of
genus Thioalkalivibrio are stable and active in a wide range of pH (up to 11) and
salinity (up to 1 M NaCl). To establish adaptation mechanisms of ONRs from
haloalkaliphilic bacteria a comparative analysis of amino acid sequences and
structures of ONRs from haloalkaliphilic bacteria and their homologues from non
halophilic neutrophilic bacteria was performed. The following adaptation
strategies were observed: (1) strategies specific for halophilic and alkaliphilic
proteins (an increase in the number of aspartate and glutamate residues and a
decrease in the number of lysine residues on the protein surface), (2) strategies
specific for halophilic proteins (an increase in the arginine content and a
decrease in the number of hydrophobic residues on the solvent-accessible protein
surface), (3) strategies specific for alkaliphilic proteins (an increase in the
area of intersubunit hydrophobic contacts). Unique adaptation mechanism inherent
in the ONRs from bacteria of genus Thioalkalivibrio was revealed (an increase in
the core in the number of tryptophan and phenylalanine residues, and an increase
in the number of small side chain residues, such as alanine and valine, in the
core).
PMID- 28510597
TI - Ubiquitylation of the acetyltransferase MOF in Drosophila melanogaster.
AB - The nuclear acetyltransferase MOF (KAT8 in mammals) is a subunit of at least two
multi-component complexes involved in transcription regulation. In the context of
complexes of the 'Non-Specific-Lethal' (NSL) type it controls transcription
initiation of many nuclear housekeeping genes and of mitochondrial genes. While
this function is conserved in metazoans, MOF has an additional, specific function
in Drosophila in the context of dosage compensation. As a subunit of the male
specific-lethal dosage compensation complex (MSL-DCC) it contributes to the
doubling of transcription output from the single male X chromosome by acetylating
histone H4. Proper dosage compensation requires finely tuned levels of MSL-DCC
and an appropriate distribution of MOF between the regulatory complexes. The
amounts of DCC formed depends directly on the levels of the male-specific MSL2,
which orchestrates the assembly of the DCC, including MOF recruitment. We found
earlier that MSL2 is an E3 ligase that ubiquitylates most MSL proteins, including
MOF, suggesting that ubiquitylation may contribute to a quality control of MOF's
overall levels and folding state as well as its partitioning between the complex
entities. We now used mass spectrometry to map the lysines in MOF that are
ubiquitylated by MSL2 in vitro and identified in vivo ubiquitylation sites of MOF
in male and female cells. MSL2-specific ubiquitylation in vivo could not be
traced due to the dominance of other, sex-independent ubiquitylation events and
conceivably may be rare or transient. Expressing appropriately mutated MOF
derivatives we assessed the importance of the ubiquitylated lysines for dosage
compensation by monitoring DCC formation and X chromosome targeting in cultured
cells, and by genetic complementation of the male-specific-lethal mof2 allele in
flies. Our study provides a comprehensive analysis of MOF ubiquitylation as a
reference for future studies.
PMID- 28510598
TI - Age, gender, neck circumference, and Epworth sleepiness scale do not predict
obstructive sleep apnea (OSA) in moderate to severe chronic obstructive pulmonary
disease (COPD): The challenge to predict OSA in advanced COPD.
AB - The combination of chronic obstructive pulmonary disease (COPD) and obstructive
sleep apnea (OSA) is associated with substantial morbidity and mortality. We
hypothesized that predictors of OSA among patients with COPD may be distinct from
OSA in the general population. Therefore, we investigated associations between
traditional OSA risk factors (e.g. age), and sleep questionnaires [e.g. Epworth
Sleepiness Scale] in 44 patients with advanced COPD. As a second aim we proposed
a pilot, simplified screening test for OSA in patients with COPD. In a
prospective, observational study of patients enrolled in the UCSD Pulmonary
Rehabilitation Program we collected baseline characteristics, cardiovascular
events (e.g. atrial fibrillation), and sleep questionnaires [e.g. Pittsburgh
Sleep Quality Index (PSQI)]. For the pilot questionnaire, a BMI >=25 kg/m2 and
the presence of cardiovascular disease were used to construct the pilot screening
test. Male: 59%; OSA 66%. FEV1 (mean +/- SD) = 41.0+/-18.2% pred., FEV1/FVC =
41.5+/-12.7%]. Male gender, older age, and large neck circumference were not
associated with OSA. Also, Epworth Sleepiness Scale and the STOP-Bang
questionnaire were not associated with OSA in univariate logistic regression. In
contrast, BMI >=25 kg/m2 (OR = 3.94, p = 0.04) and diagnosis of cardiovascular
disease (OR = 5.06, p = 0.03) were significantly associated with OSA [area under
curve (AUC) = 0.74]. The pilot COPD-OSA test (OR = 5.28, p = 0.05) and STOP-Bang
questionnaire (OR = 5.13, p = 0.03) were both associated with OSA in Receiver
Operating Characteristics (ROC) analysis. The COPD-OSA test had the best AUC
(0.74), sensitivity (92%), and specificity (83%). A ten-fold cross-validation
validated our results. We found that traditional OSA predictors (e.g. gender,
Epworth score) did not perform well in patients with more advanced COPD. Our
pilot test may be an easy to implement instrument to screen for OSA. However, a
larger validation study is necessary before further clinical implementation is
warranted.
PMID- 28510599
TI - Selective inhibition of brain endothelial Rho-kinase-2 provides optimal
protection of an in vitro blood-brain barrier from tissue-type plasminogen
activator and plasmin.
AB - Rho-kinase (ROCK) inhibition, broadly utilised in cardiovascular disease, may
protect the blood-brain barrier (BBB) during thrombolysis from rt-PA-induced
damage. While the use of nonselective ROCK inhibitors like fasudil together with
rt-PA may be hindered by possible hypotensive side-effects and inadequate
capacity to block detrimental rt-PA activity in brain endothelial cells (BECs),
selective ROCK-2 inhibition may overcome these limitations. Here, we examined
ROCK-2 expression in major brain cells and compared the ability of fasudil and
KD025, a selective ROCK-2 inhibitor, to attenuate rt-PA-induced BBB impairment in
an in vitro human model. ROCK-2 was highly expressed relative to ROCK-1 in all
human and mouse brain cell types and particularly enriched in rodent brain
endothelial cells and astrocytes compared to neurons. KD025 was more potent than
fasudil in attenuation of rt-PA- and plasminogen-induced BBB permeation under
normoxia, but especially under stroke-like conditions. Importantly, only KD025,
but not fasudil, was able to block rt-PA-dependent permeability increases,
morphology changes and tight junction degradation in isolated BECs. Selective
ROCK-2 inhibition further diminished rt-PA-triggered myosin phosphorylation,
shape alterations and matrix metalloprotease activation in astrocytes. These
findings highlight ROCK-2 as the key isoform driving BBB impairment and brain
endothelial damage by rt-PA and the potential of KD025 to optimally protect the
BBB during thrombolysis.
PMID- 28510601
TI - Reproductive biology of the deep brooding coral Seriatopora hystrix: Implications
for shallow reef recovery.
AB - Mesophotic coral ecosystems (MCEs, between 30 and 150 m depth) are hypothesized
to contribute to the recovery of degraded shallow reefs through sexually produced
larvae (referred to as Deep Reef Refuge Hypothesis). In Okinawa, Japan, the
brooder coral Seriatopora hystrix was reported to be locally extinct in a shallow
reef while it was found abundant at a MCE nearby. In this context, S. hystrix
represents a key model to test the Deep Reef Refuge Hypothesis and to understand
the potential contribution of mesophotic corals to shallow coral reef recovery.
However, the reproductive biology of mesophotic S. hystrix and its potential to
recolonize shallow reefs is currently unknown. This study reports for the first
time, different temporal scales of reproductive periodicity and larval settlement
of S. hystrix from an upper mesophotic reef (40 m depth) in Okinawa. We examined
reproductive seasonality, lunar, and circadian periodicity (based on polyp
dissection, histology, and ex situ planula release observations) and larval
settlement rates in the laboratory. Mesophotic S. hystrix reproduced mainly in
July and early August, with a small number of planulae being released at the end
of May, June and August. Compared to shallow colonies in the same region,
mesophotic S. hystrix has a 4-month shorter reproductive season, similar
circadian periodicity, and smaller planula size. In addition, most of the
planulae settled rapidly, limiting larval dispersal potential. The shorter
reproductive season and smaller planula size may result from limited energy
available for reproduction at deeper depths, while the similar circadian
periodicity suggests that this reproductive aspect is not affected by
environmental conditions differing with depth. Overall, contribution of
mesophotic S. hystrix to shallow reef rapid recovery appears limited, although
they may recruit to shallow reefs through a multistep process over a few
generations or through random extreme mixing such as typhoons.
PMID- 28510600
TI - Complete Comparison Display (CCD) evaluation of ethanol extracts of Centella
asiatica and Withania somnifera shows that they can non-synergistically
ameliorate biochemical and behavioural damages in MPTP induced Parkinson's model
of mice.
AB - Parkinson's disease remains as one of the most common debilitating
neurodegenerative disorders. With the hopes of finding agents that can cure or
reduce the pace of progression of the disease, we studied two traditional
medicinal plants: Centella asiatica and Withania somnifera that have been
explored in some recent studies. In agreement with the previous work on ethanol
extracts of these two plants in mice model, we saw an improvement in oxidative
stress profile as well as behavioral performance in 1-methyl-4-phenyl-1,2,3,6
tetrahydropyridine (MPTP) induced Parkinson-like symptoms in Balb/c mice. Given
the known potential of both the herbal extracts in improving Parkinson-like
symptoms, we expected the combination of the two to show better results than
either of the two but surprisingly there was no additivity in either oxidative
stress or behavioural recovery. In fact, in some assays, the combination
performed worse than either of the two individual constituents. This effect of
mixtures highlights the need of testing mixtures in supplements market using
enthomedicine. The necessity of comparing multiple groups in this study to get
most information from the experiments motivated us to design a ladder-like
visualization to show comparison with different groups that we call complete
comparison display (CCD). In summary, we show the potential of Centella asiatica
and Withania somnifera to ameliorate Parkinson's disorder.
PMID- 28510602
TI - Tree-based approach for exploring marine spatial patterns with raster datasets.
AB - From multiple raster datasets to spatial association patterns, the data-mining
technique is divided into three subtasks, i.e., raster dataset pretreatment,
mining algorithm design, and spatial pattern exploration from the mining results.
Comparison with the former two subtasks reveals that the latter remains
unresolved. Confronted with the interrelated marine environmental parameters, we
propose a Tree-based Approach for eXploring Marine Spatial Patterns with multiple
raster datasets called TAXMarSP, which includes two models. One is the Tree-based
Cascading Organization Model (TCOM), and the other is the Spatial Neighborhood
based CAlculation Model (SNCAM). TCOM designs the "Spatial node->Pattern node"
from top to bottom layers to store the table-formatted frequent patterns.
Together with TCOM, SNCAM considers the spatial neighborhood contributions to
calculate the pattern-matching degree between the specified marine parameters and
the table-formatted frequent patterns and then explores the marine spatial
patterns. Using the prevalent quantification Apriori algorithm and a real remote
sensing dataset from January 1998 to December 2014, a successful application of
TAXMarSP to marine spatial patterns in the Pacific Ocean is described, and the
obtained marine spatial patterns present not only the well-known but also new
patterns to Earth scientists.
PMID- 28510603
TI - Effectiveness of community-based peer support for mothers to improve their
breastfeeding practices: A systematic review and meta-analysis.
AB - METHODS: We searched for evidence regarding community-based peer support for
mothers in databases, such as PubMed/MEDLINE, the Cochrane Library, CINAHL, Web
of Science, SocINDEX, and PsycINFO. We selected three outcome variables for
breastfeeding practices, namely, exclusive breastfeeding duration, breastfeeding
within the first hour of life, and prelacteal feeding. We conducted meta-analyses
of the included randomized controlled trials and quasi-experimental studies.
RESULTS: For our review, we selected 47 articles for synthesis out of 1,855
retrieved articles. In low- and middle-income countries, compared to usual care,
community-based peer support increased exclusive breastfeeding at 3 months (RR:
1.90, 95% CI: 1.62-2.22), at 5 months (RR: 9.55, 95% CI: 6.65-13.70) and at 6
months (RR: 3.53, 95% CI: 2.49-5.00). In high-income countries, compared to usual
care, peer support increased exclusive breastfeeding at 3 months (RR: 2.61, 95%
CI: 1.15-5.95). In low- and middle-income countries, compared to usual care, peer
support increased the initiation of breastfeeding within the first hour of life
(RR: 1.51, 95% CI: 1.04-2.21) and decreased the risk of prelacteal feeding (RR:
0.38, 95% CI: 0.33-0.45). CONCLUSIONS: Community-based peer support for mothers
is effective in increasing the duration of exclusive breastfeeding, particularly
for infants aged 3-6 months in low- and middle-income countries. Such support
also encourages mothers to initiate breastfeeding early and prevents newborn
prelacteal feeding.
PMID- 28510604
TI - Ebola exposure, illness experience, and Ebola antibody prevalence in
international responders to the West African Ebola epidemic 2014-2016: A cross
sectional study.
AB - BACKGROUND: Healthcare and other front-line workers are at particular risk of
infection with Ebola virus (EBOV). Despite the large-scale deployment of
international responders, few cases of Ebola virus disease have been diagnosed in
this group. Since asymptomatic or pauci-symptomatic infection has been described,
it is plausible that infections have occurred in healthcare workers but have
escaped being diagnosed. We aimed to assess the prevalence of asymptomatic or
pauci-symptomatic infection, and of exposure events, among returned responders to
the West African Ebola epidemic 2014-2016. METHODS AND FINDINGS: We used snowball
sampling to identify responders who had returned to the UK or Ireland, and used
an online consent and questionnaire to determine their exposure to EBOV and their
experience of illness. Oral fluid collection devices were sent and returned by
post, and samples were tested using an EBOV IgG capture assay that detects IgG to
Ebola glycoprotein. Blood was collected from returnees with reactive samples for
further testing. Unexposed UK controls were also recruited. In all, 300
individuals consented, of whom 268 (89.3%) returned an oral fluid sample (OFS).
The majority had worked in Sierra Leone in clinical, laboratory, research, and
other roles. Fifty-three UK controls consented and provided samples using the
same method. Of the returnees, 47 (17.5%) reported that they had had a possible
EBOV exposure. Based on their free-text descriptions, using a published risk
assessment method, we classified 43 (16%) as having had incidents with risk of
Ebola transmission, including five intermediate-risk and one high-risk exposure.
Of the returnees, 57 (21%) reported a febrile or diarrhoeal illness in West
Africa or within 1 mo of return, of whom 40 (70%) were not tested at the time for
EBOV infection. Of the 268 OFSs, 266 were unreactive. Two returnees, who did not
experience an illness in West Africa or on return, had OFSs that were reactive on
the EBOV IgG capture assay, with similar results on plasma. One individual had no
further positive test results; the other had a positive result on a double
antigen bridging assay but not on a competitive assay or on an indirect EBOV IgG
ELISA. All 53 controls had non-reactive OFSs. While the participants were not a
random sample of returnees, the number participating was high. CONCLUSIONS: This
is the first study, to our knowledge, of the prevalence of EBOV infection in
international responders. More than 99% had clear negative results. Sera from two
individuals had discordant results on the different assays; both were negative on
the competitive assay, suggesting that prior infection was unlikely. The finding
that a significant proportion experienced "near miss" exposure events, and that
most of those who experienced symptoms did not get tested for EBOV at the time,
suggests a need to review and standardise protocols for the management of
possible exposure to EBOV, and for the management of illness, across
organisations that deploy staff to outbreaks.
PMID- 28510605
TI - The role of attention in human motor resonance.
AB - Observation of others' actions evokes in primary motor cortex and spinal circuits
of observers a subliminal motor resonance response, which reflects the motor
program encoding observed actions. We investigated the role of attention in human
motor resonance with four experimental conditions, explored in different subject
groups: in the first explicit condition, subjects were asked to observe a
rhythmic hand flexion-extension movement performed live in front of them. In two
other conditions subjects had to monitor the activity of a LED light mounted on
the oscillating hand. The hand was clearly visible but it was not the focus of
subjects' attention: in the semi-implicit condition hand movement was relevant to
task completion, while in the implicit condition it was irrelevant. In a fourth,
baseline, condition subjects observed the rhythmic oscillation of a metal
platform. Motor resonance was measured with the H-reflex technique as the
excitability modulation of cortico-spinal motorneurons driving a hand flexor
muscle. As expected, a normal resonant response developed in the explicit
condition, and no resonant response in the baseline condition. Resonant responses
also developed in both semi-implicit and implicit conditions and, surprisingly,
were not different from each other, indicating that viewing an action is, per se,
a powerful stimulus for the action observation network, even when it is not the
primary focus of subjects' attention and even when irrelevant to the task.
However, the amplitude of these responses was much reduced compared to the
explicit condition, and the phase-lock between the time courses of observed
movement and resonant motor program was lost. In conclusion, different parameters
of the response were differently affected by subtraction of attentional resources
with respect to the explicit condition: time course and muscle selection were
preserved while the activation of motor circuits resulted in much reduced
amplitude and lost its kinematic specificity.
PMID- 28510606
TI - Safety and efficacy of cell-free and concentrated ascites reinfusion therapy
(CART) in refractory ascites: Post-marketing surveillance results.
AB - We performed post-marketing surveillance to evaluate the safety and efficacy of
cell-free and concentrated ascites reinfusion therapy (CART). In total, 356 CART
sessions in 147 patients at 22 centers were performed. The most common primary
disease was cancer (128 cases, 300 sessions). Mean amount of ascites collected
was 3.7 L, and mean concentration ratio was 9.2. Mean amount of reinfused protein
was 67.8 g (recovery rate, 72.0%). Performance status, dietary intake, urine
volume, body weight and abdominal circumference were significantly improved after
CART. Body temperature increased significantly, by 0.3 degrees C on average.
Concomitant steroids and/or NSAIDs use before reinfusion was significantly and
negatively associated with increases in body temperature. Most adverse events
were fever and chills. This study examined a large number of patients compared
with previous studies, and showed that CART is an effective and relatively safe
treatment for refractory ascites, such as malignant ascites.
PMID- 28510607
TI - Recent evolutionary history of Chrysoperla externa (Hagen 1861) (Neuroptera:
Chrysopidae) in Brazil.
AB - This work aimed to elucidate the distribution of Chrysoperla externa haplotypes
and investigate whether it exhibits structure based on genetic composition as
opposed to geographic location. The genetic diversity of C. externa, analyzed by
AMOVA using the COI and 16S rRNA genes as mitochondrial markers, showed
significant haplotype structure arising from genetic differences that was not
associated with sampling location. This was reflected in the network grouping.
Bayesian inference showed that haplotype distribution may have its origins in C.
externa divergence into two distinct clades, which dispersed to various
locations, and their subsequent diversification. The evolutionary history of C.
externa may include multiple ancestral haplotypes differentiating within the same
geographic area to generate the current broad genetic diversity, so that the
earlier geographical history has been erased, and now we have highlighted its
more recent genetic history.
PMID- 28510609
TI - SPR-based fragment screening with neurotensin receptor 1 generates novel small
molecule ligands.
AB - The neurotensin receptor 1 represents an important drug target involved in
various diseases of the central nervous system. So far, the full exploitation of
potential therapeutic activities has been compromised by the lack of compounds
with favorable physicochemical and pharmacokinetic properties which efficiently
penetrate the blood-brain barrier. Recent progress in the generation of
stabilized variants of solubilized neurotensin receptor 1 and its subsequent
purification and successful structure determination presents a solid starting
point to apply the approach of fragment-based screening to extend the chemical
space of known neurotensin receptor 1 ligands. In this report, surface plasmon
resonance was used as primary method to screen 6369 compounds. Thereby 44 hits
were identified and confirmed in competition as well as dose-response
experiments. Furthermore, 4 out of 8 selected hits were validated using nuclear
magnetic resonance spectroscopy as orthogonal biophysical method. Computational
analysis of the compound structures, taking the known crystal structure of the
endogenous peptide agonist into consideration, gave insight into the potential
fragment-binding location and interactions and inspires chemistry efforts for
further exploration of the fragments.
PMID- 28510608
TI - The Biomphalaria glabrata DNA methylation machinery displays spatial tissue
expression, is differentially active in distinct snail populations and is
modulated by interactions with Schistosoma mansoni.
AB - BACKGROUND: The debilitating human disease schistosomiasis is caused by infection
with schistosome parasites that maintain a complex lifecycle alternating between
definitive (human) and intermediate (snail) hosts. While much is known about how
the definitive host responds to schistosome infection, there is comparably less
information available describing the snail's response to infection.
METHODOLOGY/PRINCIPLE FINDINGS: Here, using information recently revealed by
sequencing of the Biomphalaria glabrata intermediate host genome, we provide
evidence that the predicted core snail DNA methylation machinery components are
associated with both intra-species reproduction processes and inter-species
interactions. Firstly, methyl-CpG binding domain protein (Bgmbd2/3) and DNA
methyltransferase 1 (Bgdnmt1) genes are transcriptionally enriched in gonadal
compared to somatic tissues with 5-azacytidine (5-AzaC) treatment significantly
inhibiting oviposition. Secondly, elevated levels of 5-methyl cytosine (5mC), DNA
methyltransferase activity and 5mC binding in pigmented hybrid- compared to
inbred (NMRI)- B. glabrata populations indicate a role for the snail's DNA
methylation machinery in maintaining hybrid vigour or heterosis. Thirdly, locus
specific detection of 5mC by bisulfite (BS)-PCR revealed 5mC within an exonic
region of a housekeeping protein-coding gene (Bg14-3-3), supporting previous in
silico predictions and whole genome BS-Seq analysis of this species' genome.
Finally, we provide preliminary evidence for parasite-mediated host epigenetic
reprogramming in the schistosome/snail system, as demonstrated by the increase in
Bgdnmt1 and Bgmbd2/3 transcript abundance following Bge (B. glabrata embryonic
cell line) exposure to parasite larval transformation products (LTP).
CONCLUSIONS/SIGNIFICANCE: The presence of a functional DNA methylation machinery
in B. glabrata as well as the modulation of these gene products in response to
schistosome products, suggests a vital role for DNA methylation during snail
development/oviposition and parasite interactions. Further deciphering the role
of this epigenetic process during Biomphalaria/Schistosoma co-evolutionary
biology may reveal key factors associated with disease transmission and,
moreover, enable the discovery of novel lifecycle intervention strategies.
PMID- 28510611
TI - MMP-10, MMP-7, TIMP-1 and TIMP-2 mRNA expression in esophageal cancer.
AB - INTRODUCTION: Tissue inhibitors of metalloproteinases (TIMP) and the matrix
metalloproteinases (MMP) are involved in the spread of cancer. METHODS: We have
evaluated the matrix metalloproteinases' (MMP-10, MMP-7) and their inhibitors'
(tissue inhibitors of metalloproteinases - TIMP-1, TIMP-2) mRNA expression in 61
esophageal cancer samples from patients who had undergone surgery, by using real
time quantitative RT-PCR, and correlated the results with the patient
clinicopathologic features. RESULTS: MMP-10, MMP-7, TIMP-1, TIMP-2 were
overexpressed in 73%, 85%, 55% and 42% of esophageal cancer samples,
respectively. The expression of MMP-10, TIMP-1, and TIMP-2 correlated with the
tumor size. The MMP-7 overexpression was associated with the tumour stage (I, II
vs III, p=0.05) and lymph node metastasis (N0 vs N1, p=0.037). CONCLUSIONS: We
conclude that in the resected esophageal cancer an increased mRNA expression of
MMP-7, MMP-10 and TIMP-1 correlated with clinicopathologic features. We suggest
that these genes may play a role during progression of the disease.
PMID- 28510610
TI - Insulin resistance contributes more to the increased risk for diabetes
development in subjects with low lipoprotein(a) level than insulin secretion.
AB - BACKGROUND: Recent studies suggest an association between Lipoprotein(a) [Lp(a)]
and the development of diabetes mellitus. We analyzed the association between
baseline Lp(a) levels and diabetes development after 4 years of follow-up, in a
population of apparently healthy Korean subjects. METHODS: A total of 2,536 non
diabetic participants (mean age: 41 years, men: 92%) of a health checkup program
were included in the study. Diabetes development was defined by fasting blood
glucose >=126 mg/dL, HbA1c >=6.5%, and self-reported treatment of diabetes.
Homeostasis model assessment (HOMA) indices were used to assess insulin
resistance (IR) and insulin secretion (IS). Presence of IR and impaired IS was
defined by being in the highest quartile of HOMA-IR and in the lowest quartile
HOMA-IS. RESULTS: After four years, 3.4% of the participants developed diabetes.
The odds ratio (OR) of developing diabetes was lowest in the 4th quartile group
of baseline Lp(a) (0.323 [95% CI 0.153-0.685])with the 1st quartile group as the
reference. The subjects with both IR & impaired IS plus baseline Lp(a)<50 mg/dL
showed the higher OR for diabetes development compared with those without IR and
normal IS as the reference (67.277 [20.218-223.871], and those with IR plus
Lp(a)<50 mg/dL showed higher OR for diabetes than in those with impaired IS and
Lp(a)<50 mg/dL (3.811 [1.938-7.495] vs. 3.452 [1.620-7.353]). CONCLUSIONS: The
subjects with low baseline Lp(a) level showed higher risk for development of
diabetes compared with high baseline Lp(a) level, and this was prominent in those
with IR than in those with impaired IS.
PMID- 28510613
TI - Preliminary report on beta-casein gene Met183QVal183 polymorphism in Romanian
indigenous Zackel sheep breeds.
AB - Genetic polymorphisms of the milk protein genes are important because of their
effects on quantitative traits and technological properties of milk
manufacturing. In the present study we identified the polymorphism of the beta
casein gene in two local sheep breeds (Racka n=98 and Turcana n=111) in Romania.
The most studied variants at the ovine beta-casein (CSN2) locus are: A and G
variants. Genomic DNA was extracted from hair follicles and beta-casein genotypes
were determined by the rapid TaqMan (Applied Biosystems, USA) genotyping assay.
Homozygote genotypes GG were not detected in any of the studied breeds. In both,
the Racka and Turcana breeds, the A variant had a much higher frequency, 0.98%
and 0.97%, respectively. In the current study, the fast DNA tests for genotyping
ovine CSN2 were successfully optimized, however, further samples and correlations
of genomic results with milk characteristics and production data are needed for
the development of future selection schemes of the Romanian indigenous sheep
breeds, with the ultimate purpose to produce low allergen level sheep milk and
derived dairy products.
PMID- 28510612
TI - Suppression of ID1 expression in colon cancer cells increases sensitivity to 5
fluorouracil.
AB - Adjuvant chemotherapy with 5-fluorouracil remains the basic treatment for
patients with advanced colorectal carcinoma. The major obstacle in successful
treatment is the ability of CRC cells to acquire chemoresistance. Here we
examined the impact of ID1 silencing on the sensitivity of CRC cells to 5-FU. To
suppress ID1 expression in HT-29 and HCT-116 cells the cells were transduced with
a lentiviral vector carrying the ID1 silencing sequence. Cells with silenced ID1
showed altered expression of epithelial and mesenchymal markers and exhibited
increased proliferation rate compared to the parental cells. HCT-116 cells with
suppressed ID1 became sensitized to 5-FU and this was not observed in HT-29
cells. Silencing ID1 resulted in altered expression of genes encoding enzymes
metabolizing 5-FU. HT-29 cells with suppressed ID1 had significantly reduced mRNA
level for thymidine phosphorylase, uridine-cytydine kinase 2 and
dihydropyrimidine dehydrogenase. ID1 suppression in HCT-116 cells resulted in an
increase of mRNA level for thymidine phosphorylase, thymidine kinase and uridine
cytydine kinase 2 with concurrent drop of dihydropyrimidine dehydrogenase and
thymidylate synthetase mRNA levels. In conclusion, ID1 expression impacts the
sensitivity of colon cancer cells to 5-FU and may be considered as a potential
predictive marker in CRC treatment.
PMID- 28510614
TI - Connexin-dependent intercellular stress signaling in tissue homeostasis and tumor
development.
AB - : Cellular stress responses determine tissue development, homeostasis and
pathogenesis. Paracrine signaling, exchange of mechanical stimuli and
intercellular transfer of small metabolites via connexin-built gap junctional
channels are involved in the cellular stress detection and propagation of stress
stimuli in multicellular networks. Cellular stress responses are also regulated
through the activity of unpaired connexons (hemichannels) and via the
intracellular interference of connexins with the cell cycle and pro-apoptotic
machinery. Therefore, connexins are considered as multidirectional transmitters
of the "outside-in" and "inside-out" stress signaling that are crucial for tissue
homeostasis, regeneration and pathology. In particular, the disturbance of
connexin function during the multi-stage process of tumor development leads to
abnormal reactions of tumor cells to stress stimuli. In this review, we outline
the current knowledge on the multidirectional role of connexins in the detection
of stress signals. We also discuss the role of connexin-mediated intercellular
transmittance of stress signals in tumour promotion, progression and metastatic
cascade. HIGHLIGHTS: 1. Connexins and gap junctions protect cells from the
microenvironmental stress and are involved in propagation and intracellular
processing of stress signals. 2. The quality and quantity of stress stimuli,
which may lead to cell adaptation or death by apoptosis, is determined by
intrinsic properties of connexins and the cell phenotype. 3. Connexin deficiency
increases the resistance of tumor cells to the "outside-in" stress signaling. 4.
The connexin-mediated "inside-out" stress signaling participates in tumor cell
invasion during the metastatic cascade.
PMID- 28510615
TI - The Role of Frequency in Learning Morphophonological Alternations: Implications
for Children With Specific Language Impairment.
AB - Purpose: The aim of this article was to explore how the type of allomorph (e.g.,
past tense buzz[d] vs. nod[ed]) influences the ability to perceive and produce
grammatical morphemes in children with typical development and with specific
language impairment (SLI). Method: The participants were monolingual Australian
English-speaking children. The SLI group included 13 participants (mean age = 5;7
[years;months]); the control group included 19 children with typical development
(mean age = 5;4). Both groups performed a grammaticality judgment and elicited
production task with the same set of nonce verbs in third-person singular and
past tense forms. Results: Five-year-old children are still learning to
generalize morphophonological patterns to novel verbs, and syllabic /ez/ and /ed/
allomorphs are significantly more challenging to produce, particularly for the
SLI group. The greater phonetic content of these syllabic forms did not enhance
perception. Conclusions: Acquisition of morphophonological patterns involving low
frequency allomorphs is still underway in 5-year-old children with typical
development, and it is even more protracted in SLI populations, despite these
patterns being highly predictable. Children with SLI will therefore benefit from
targeted intervention with low-frequency allomorphs.
PMID- 28510616
TI - Salvage high-dose chemotherapy in female patients with relapsed/refractory germ
cell tumors: a retrospective analysis of the European Group for Blood and Marrow
Transplantation (EBMT).
AB - Background: High-dose chemotherapy (HDC) with hematopoietic progenitor cell
transplantation is a standard option for relapsed/refractory testicular germ-cell
tumor (GCT), but only few data have been reported in female patients with GCT. We
conducted a retrospective analysis of female patients with GCT treated with HDC
and registered with the European Society for Blood and Marrow Transplantation.
Patients and methods: Between 1985 and 2013, 60 registered female patients with
GCT, median age 27 years (range 15-48), were treated with salvage HDC. Forty
patients (67%) had primary ovarian GCT, 8 (13%) mediastinal, 7 (12%)
retroperitoneal and 5 (8%) other primary sites/unknown. Twenty-two patients (37%)
received HDC as second-line therapy, 29 (48%) as third-line, and 9 (15%) as
fourth- to sixth-line. Nine of 60 patients (15%) received HDC as late
intensification with no evidence of metastasis before HDC. The conditioning HDC
regimens comprised carboplatin in 51 of 60 cases (85%), and consisted of a single
HDC cycle in 31 cases (52%), a multi-cycle HDC regimen in 29 (48%). Results: Nine
cases who underwent late intensification HDC were not evaluable for response. Of
the other 51 assessable patients, 17 (33%) achieved a complete response (CR), 8
(16%) a marker-negative partial remission (PRm-), 5 (10%) a marker-positive
partial remission, 5 (10%) stable disease, and 13 (25%) progressive disease.
There were 3 toxic deaths (6%). With an overall median follow-up of 14 months
(range 1-219), 7 of 9 (78%) patients with late intensification and 18 of the 25
patients (72%) achieving a CR/PRm- following HDC were free of
relapse/progression. In total, 25 of 60 patients (42%) were progression-free
following HDC at a median follow-up of 87 months (range 3-219 months).
Conclusions: Salvage HDC based on carboplatin represents a therapeutic option for
female patients with relapsed/refractory GCT.
PMID- 28510617
TI - miR-146a-5p acts as a negative regulator of TGF-beta signaling in skeletal muscle
after acute contusion.
AB - Growing evidence suggests the importance of microRNAs (miRNAs) in stress
signaling pathways. Transforming growth factor-beta (TGF-beta) is a potent
cytokine that promotes the development of skeletal muscle fibrosis after acute
contusion. However, how miRNAs are involved in TGF-beta signaling and confer the
robustness of TGF-beta-induced fibrotic response remains to be fully elucidated.
Here, we demonstrated that miR-146a-5p (miR-146) levels were reduced in a
fibrotic mouse model after acute muscle contusion. It was also found that TGF
beta treatment decreased the expression of miR-146 in vitro in a dose- and time
dependent manner. In addition, overexpression of Smad3 and Samd4, two key players
in TGF-beta signaling, suppressed the expression of miR-146 in muscle cells.
Overexpression of miR-146 inhibited the expressions of fibrosis markers both in
vitro and in vivo. Moreover, increase in the expression of miR-146 in muscle
cells was able to attenuate the effect of TGF-beta on the expressions of fibrosis
markers. Mechanistic analysis revealed that Smad4 is a direct target of miR-146
in muscle cells. Furthermore, the anti-fibrotic effect of miR-146 could be
blocked by overexpression of Smad4 in vivo. These results suggest that Smad4 is
down-regulated by miR-146 in skeletal muscle. Taken together, our results
indicate that the anti-fibrotic miR-146 is a component of TGF-beta signaling. It
is down-regulated by Smad protein, and can inhibit the expression of Smad4. Our
study suggests that miR-146 might have a therapeutic potential to reduce skeletal
muscle fibrosis after injury.
PMID- 28510618
TI - Auditory Processing of Older Adults With Probable Mild Cognitive Impairment.
AB - Purpose: Studies suggest that deficits in auditory processing predict cognitive
decline and dementia, but those studies included limited measures of auditory
processing. The purpose of this study was to compare older adults with and
without probable mild cognitive impairment (MCI) across two domains of auditory
processing (auditory performance in competing acoustic signals and temporal
aspects of audition). Method: The Montreal Cognitive Assessment (Nasreddine et
al., 2005) was used to classify participants as with or without probable MCI. In
this cross-sectional study, participants (n = 79) completed 4 measures of
auditory processing: Synthetic Sentence Identification with Ipsilateral Competing
Message (Gates, Beiser, Rees, D'Agostino, & Wolf, 2002), Dichotic Sentence
Identification (Fifer, Jerger, Berlin, Tobey, & Campbell, 1983), Adaptive Tests
of Temporal Resolution (ATTR; Lister & Roberts, 2006; across-channel and within
channel subtests), and time-compressed speech (Wilson, 1993; Wilson, Preece,
Salamon, Sperry, & Bornstein, 1994). Audiometry was also conducted. Results:
Those with probable MCI had significantly poorer performance than those without
MCI on Synthetic Sentence Identification with Ipsilateral Competing Message,
Dichotic Sentence Identification, and the ATTR within-channel subtest. No group
differences were found for time-compressed speech, ATTR across-channel, or
audiometric measures. Conclusions: Older adults with cognitive impairment not
only have difficulty with competing acoustic signals but may also show poor
temporal processing. The profile of auditory processing deficits among older
adults with cognitive impairment may include multiple domains.
PMID- 28510619
TI - Diabetes and Cognitive Decline in Older Adults: The Ginkgo Evaluation of Memory
Study.
AB - Background: Previous studies have shown that individuals with diabetes exhibit
accelerated cognitive decline. However, methodological limitations have limited
the quality of this evidence. Heterogeneity in study design, cognitive test
administration, and methods of analysis of cognitive data have made it difficult
to synthesize and translate findings to practice. We analyzed longitudinal data
from the Ginkgo Evaluation of Memory Study to test our hypothesis that older
adults with diabetes have greater test-specific and domain-specific cognitive
declines compared to older adults without diabetes. Methods: Tests of memory,
visuo-spatial construction, language, psychomotor speed, and executive function
were administered. Test scores were standardized to z-scores and averaged to
yield domain scores. Linear random effects models were used to compare baseline
differences and changes over time in test and domain scores among individuals
with and without diabetes. Results: Among the 3,069 adults, aged 72-96 years,
9.3% reported diabetes. Over a median follow-up of 6.1 years, participants with
diabetes exhibited greater baseline differences in a test of executive function
(trail making test, Part B) and greater declines in a test of language (phonemic
verbal fluency). For the composite cognitive domain scores, participants with
diabetes exhibited lower baseline executive function and global cognition domain
scores, but no significant differences in the rate of decline. Conclusions:
Identifying cognitive domains most affected by diabetes can lead to targeted risk
modification, possibly in the form of lifestyle interventions such as diet and
physical activity, which we know to be beneficial for improving vascular risk
factors, such as diabetes, and therefore may reduce the risk of executive
dysfunction and possible dementia.
PMID- 28510620
TI - Association Between Neighborhood Supermarket Presence and Glycated Hemoglobin
Levels Among Patients With Type 2 Diabetes Mellitus.
AB - We estimated associations between neighborhood supermarket gain or loss and
glycemic control (assessed by glycated hemoglobin (HbA1c) values) in patients
from the Kaiser Permanente Northern California Diabetes Registry (n = 434,806
person-years; 2007-2010). Annual clinical measures were linked to metrics from a
geographic information system for each patient's address of longest residence. We
estimated the association between change in supermarket presence (gain, loss, or
no change) and change in HbA1c value, adjusting for individual- and area-level
attributes and according to baseline glycemic control (near normal, <6.5%; good,
6.5%-7.9%; moderate, 8.0%-8.9%; and poor, >=9.0%). Supermarket loss was
associated with worse HbA1c trajectories for those with good, moderate, and poor
glycemic control at baseline, while supermarket gain was associated with
marginally better HbA1c outcomes only among patients with near normal HbA1c
values at baseline. Patients with the poorest baseline HbA1c values (>=9.0%) had
the worst associated changes in glycemic control following either supermarket
loss or gain. Differences were not clinically meaningful relative to no change in
supermarket presence. For patients with type 2 diabetes mellitus, gaining
neighborhood supermarket presence did not benefit glycemic control in a
substantive way. The significance of supermarket changes on health depends on a
complex interaction of resident, neighborhood, and store characteristics.
PMID- 28510621
TI - miR-290 contributes to the low abundance of cyclin D1 protein in mouse embryonic
stem cells.
AB - Mouse miR-290 cluster miRNAs are expressed specifically in early embryos and
embryonic germ cells. These miRNAs play critical roles in the maintenance of
pluripotency and self-renewal. Here, we showed that Cyclin D1 is a direct target
gene of miR-290 cluster miRNAs. Negative relationships between the expression of
Cyclin D1 protein and miR-290 cluster miRNAs in pluripotent and non-pluripotent
cells, as well as in differentiating CGR8 cells were observed. Inhibition of miR
290 cluster miRNAs could arrest cells at the G1 phase and slow down the cell
proliferation in CGR8 mouse stem cells. Since miR-290 cluster miRNAs are the most
dominant stem-cell-specific miRNAs, our results revealed an important cause for
the absence of Cyclin D1 in mouse embryonic stem cells.
PMID- 28510622
TI - Development and validation of a noncontact spectroscopic device for hemoglobin
estimation at point-of-care.
AB - Anemia severely and adversely affects human health and socioeconomic development.
Measuring hemoglobin with the minimal involvement of human and financial
resources has always been challenging. We describe a translational spectroscopic
technique for noncontact hemoglobin measurement at low-resource point-of-care
settings in human subjects, independent of their skin color, age, and sex, by
measuring the optical spectrum of the blood flowing in the vascular bed of the
bulbar conjunctiva. We developed software on the LabVIEW platform for automatic
data acquisition and interpretation by nonexperts. The device is calibrated by
comparing the differential absorbance of light of wavelength 576 and 600 nm with
the clinical hemoglobin level of the subject. Our proposed method is consistent
with the results obtained using the current gold standard, the automated
hematology analyzer. The proposed noncontact optical device for hemoglobin
estimation is highly efficient, inexpensive, feasible, and extremely useful in
low-resource point-of-care settings. The device output correlates with the
different degrees of anemia with absolute and trending accuracy similar to those
of widely used invasive methods. Moreover, the device can instantaneously
transmit the generated report to a medical expert through e-mail, text messaging,
or mobile apps.
PMID- 28510623
TI - Sensing of Streptococcus mutans by microscopic imaging ellipsometry.
AB - Microscopic imaging ellipsometry is an optical technique that uses an objective
and sensing procedure to measure the ellipsometric parameters ? and ? in the form
of microscopic maps. This technique is well known for being noninvasive and label
free. Therefore, it can be used to detect and characterize biological species
without any impact. Microscopic imaging ellipsometry was used to measure the
optical response of dried Streptococcus mutans cells on a glass substrate. The
ellipsometric ? and ? maps were obtained with the Optrel Multiskop system for
specular reflection in the visible range ( ? = 450 to 750 nm). The ? and ? images
at 500, 600, and 700 nm were analyzed using three different theoretical models
with single-bounce, two-bounce, and multibounce light paths to obtain the optical
constants and height distribution. The obtained images of the optical constants
show different aspects when comparing the single-bounce analysis with the two
bounce or multibounce analysis in detecting S. mutans samples. Furthermore, the
height distributions estimated by two-bounce and multibounce analyses of S.
mutans samples were in agreement with the thickness values measured by AFM, which
implies that the two-bounce and multibounce analyses can provide information
complementary to that obtained by a single-bounce light path.
PMID- 28510624
TI - Chromatic interocular-switch rivalry.
AB - Interocular-switch rivalry (also known as stimulus rivalry) is a kind of
binocular rivalry in which two rivalrous images are swapped between the eyes
several times a second. The result is stable periods of one image and then the
other, with stable intervals that span many eye swaps (Logothetis, Leopold, &
Sheinberg, 1996). Previous work used this close kin of binocular rivalry with
rivalrous forms. Experiments here test whether chromatic interocular-switch
rivalry, in which the swapped stimuli differ in only chromaticity, results in
slow alternation between two colors. Swapping equiluminant rivalrous
chromaticities at 3.75 Hz resulted in slow perceptual color alternation, with one
or the other color often continuously visible for two seconds or longer (during
which there were 15+ eye swaps). A well-known theory for sustained percepts from
interocular-switch rivalry with form is inhibitory competition between binocular
neurons driven by monocular neurons with matched orientation tuning in each eye;
such binocular neurons would produce a stable response when a given orientation
is swapped between the eyes. A similar model can account for the percepts here
from chromatic interocular-switch rivalry and is underpinned by the
neurophysiological finding that color-preferring binocular neurons are driven by
monocular neurons from each eye with well-matched chromatic selectivity (Peirce,
Solomon, Forte, & Lennie, 2008). In contrast to chromatic interocular-switch
rivalry, luminance interocular-switch rivalry with swapped stimuli that differ in
only luminance did not result in slowly alternating percepts of different
brightnesses.
PMID- 28510625
TI - Rethinking ADA signage standards for low-vision accessibility.
AB - Americans With Disabilities Act (ADA) and International Code Council (ICC)
standards for accessible buildings and facilities affect design and construction
of all new and renovated buildings throughout the United States, and form the
basis for compliance with the ADA. While these standards may result in acceptable
accessibility for people who are fully blind, they fall far short of what they
could and should accomplish for those with low vision. In this article I critique
the standards, detailing their lack of evidence base and other shortcomings. I
suggest that simply making existing requirements stricter (e.g., by mandating
larger letter size or higher contrasts) will not ensure visual accessibility and
therefore cannot act as a valid basis for compliance with the law. I propose two
remedies. First, requirements for visual characteristics of signs intended to
improve access for those with low vision should be expressed not in terms of
physical features, such as character height and contrast, but rather in terms of
the distance at which a sign can be read by someone with nominally normal (20/20)
visual acuity under expected lighting conditions for the installed environment.
This would give sign designers greater choice in design parameters but place on
them the burden of ensuring legibility. Second, mounting of directional signs,
which are critical for effective and efficient wayfinding, should be required to
be in consistent and approachable locations so that those with reduced acuity may
view them at close distance.
PMID- 28510627
TI - Erratum.
PMID- 28510626
TI - Outcome Measures for Clinical Trials of Leber Congenital Amaurosis Caused by the
Intronic Mutation in the CEP290 Gene.
AB - Purpose: To determine efficacy outcome measures for clinical trials of Leber
congenital amaurosis (LCA) associated with a common intronic mutation in the
CEP290 gene. Methods: CEP290-LCA patients (ages 5-48) with the intronic mutation
(c.2991+1655A>G) were studied as a retrospective observational case series using
clinical methods and with full-field sensitivity testing (FST), optical coherence
tomography (OCT), autofluorescence imaging (NIR-RAFI), transient pupillary light
reflex (TPLR), oculomotor control and instability (OCI), a mobility course, and a
questionnaire (NEI-VFQ). Patients were investigated cross-sectionally but a
subset was able to be followed longitudinally. Results: With FST, there was no
rod function; cone sensitivities had a wide range from not detectable to near
normal. OCT analyses indicated retained central photoreceptors with abnormal
distal laminae. Based on OCT and FST, most patients had dissociation of structure
and function. TPLR was nondetectable in the majority of patients, with responders
demonstrating severe losses in light sensitivity. OCI was abnormal in most
patients. NEI-VFQ scores had a similar range to those of other severe
retinopathies. Mobility scores were consistent with FST sensitivities. In
patients examined with FST, OCT, and NIR-RAFI over long-term intervals (7-10
years), there was limited but detectable disease progression. Conclusions:
Efficacy would be a quantitative change in foveal cone function and possibly
distal laminar structure. FST provides a subjective photoreceptor-based outcome;
OCT and NIR-RAFI can assess photoreceptor and RPE structure. TPLR and OCI can
provide objective measures of postretinal transmission. Minimal change over a
decade indicates that there is no practical value in natural history studies.
PMID- 28510628
TI - Erratum.
PMID- 28510630
TI - Local and Systemic Inflammatory Biomarkers of Diabetic Retinopathy: An
Integrative Approach.
AB - Purpose: To review the usefulness of local and systemic inflammatory biomarkers
of diabetic retinopathy (DR) to implement a more personalized treatment. Methods:
An integrated research (from ophthalmologist and diabetologist point of view) of
most significant literature on serum, vitreous, and aqueous humor (AH)
biochemical biomarkers related to inflammation at early and advanced stages of DR
(including diabetic macular edema [DME] and proliferative DR) was performed.
Moreover, novel imaging retinal biomarkers of local "inflammatory condition" were
described. Results: Multiple inflammatory cytokines and chemokines are increased
in DR in both serum as well as in the eye (vitreous and AH). Nevertheless, local
rather than systemic production of proinflammatory cytokines seems more relevant
in the pathogenesis of both DR and DME. In the eye, retinal glia cells (macroglia
and microglia) together with RPE are major sources of proinflammatory and
angiogenic modulators. Retinal imaging allows for noninvasive clinical evaluation
of retinal inflammatory response induced by diabetes mellitus. Conclusions:
Proinflammatory cytokines/chemokines play an essential role in the pathogenesis
of DR. Therefore, circulating biomarkers and retinal imaging aimed at assessing
inflammation have emerged as useful tools for monitoring the onset and
progression of DR. In addition, "liquid biopsy" of AH seems a good option in
patients with advanced stages of DR requiring intravitreous injections. This
strategy may permit us to implement a more personalized treatment with better
visual function outcome. Further evaluation and validation of circulating and
local biomarkers, as well as multimodal imaging is needed to gain new insights
into this issue.
PMID- 28510629
TI - Fibroblast Growth Factor Receptor 2 (FGFR2) Is Required for Meibomian Gland
Homeostasis in the Adult Mouse.
AB - Purpose: Little is known about the signaling mechanisms controlling meibomian
gland (MG) homeostasis and the pathogenic processes leading to MG atrophy and
dysfunction in dry eye disease (DED). We investigated the role of fibroblast
growth factor receptor 2 (FGFR2) in the MG homeostasis of adult mice. Methods: A
triple transgenic mouse strain (Krt14-rtTA; tetO-Cre; Fgfr2flox/flox), referred
to as Fgfr2CKO mice, was generated in which the Fgfr2 gene is ablated by Cre
recombinase in keratin 14 (Krt14)-expressing epithelial cells on doxycycline
(Dox) induction. FGFR2 expression in normal human and mouse MGs was evaluated by
immunohistochemistry. Pathologic MG changes in transgenic mice with conditional
deletion of FGFR2 were examined by lipid staining, histology, and immunostaining.
Results: FGFR2 was highly expressed in normal human MGs and adult mouse MGs. Two
month-old Fgfr2CKO mice fed Dox-containing chow for 2 weeks developed severe MG
atrophy. MG acinar atrophy in the Fgfr2CKO mice was associated with reduced lipid
(meibum) production and the development of clinical findings similar to those in
humans with evaporative DED related to MG dysfunction (MGD). Immunohistochemical
analyses showed that FGFR2 deletion severely affected proliferation and
differentiation of MG acinar cells but affected MG ductal cells to a lesser
extent. Conclusions: FGFR2 deletion results in significant MG acinar atrophy and
clinical manifestations of MGD in Fgfr2CKO mice, suggesting that MG homeostasis
is FGFR2 dependent. The Fgfr2CKO mice with inducible MG atrophy can serve as a
valuable animal model for investigating the pathogenesis of MGD and developing
novel therapeutic strategies for MGD-related DED.
PMID- 28510632
TI - Hepatitis C Virus Relapse 78 Weeks After Completion of Successful Direct-Acting
Therapy.
PMID- 28510631
TI - How might edaphic specialists in gypsum islands respond to climate change?
Reciprocal sowing experiment to infer local adaptation and phenotypic plasticity.
AB - Background and Aims: Local adaptation and phenotypic plasticity are considered
key mechanisms for coping with climate warming, especially for plant species that
inhabit island-like habitats. In Spain a complete guild of edaphic specialists,
most of them threatened, occurs in gypsum outcrops, but how these species will
respond to climate change has received little attention. Methods: A reciprocal
sowing experiment was performed to determine the extent of local adaptation and
phenotypic plasticity in five gypsophytes with contrasting distributions along a
climate gradient. Germination, seedling growth and survival were recorded during
a 4-year period. Key Results: Plants responded plastically according to their
positions along the regional climate gradient, as well as locally between matched
locations. All species exhibited highly plastic responses and stress-tolerant
behaviours, especially in terms of seedling survival during summer drought.
However, no evidence of local adaptation was detected in any of the locations,
where local individuals never performed better than those from other sites. In
some sites, both germination and seedling recruitment were higher irrespective of
parent plant origin. Conclusions: The lack of local adaptation to drought
displayed at the regeneration stage indicates limited capacity for in situ
genetic response to new climate scenarios. Nevertheless, a plastic response along
the climatic gradient does suggest a wider species-level capacity to enable these
edaphic specialists to cope with increasing aridity over coming decades.
PMID- 28510634
TI - Autologous Adipose-Derived Tissue Matrix Part I: Biologic Characteristics.
AB - Background: Autologous collagen is an ideal soft tissue filler and may serve as a
matrix for stem cell implantation and growth. Procurement of autologous collagen
has been limited, though, secondary to a sufficient source. Liposuction is a
widely performed and could be a source of autologous collagen. Objectives: The
amount of collagen and its composition in liposuctioned fat remains unknown. The
purpose of this research was to characterize an adipose-derived tissue-based
product created using ultrasonic cavitation and cryo-grinding. This study
evaluated the cellular and protein composition of the final product. Methods: Fat
was obtained from individuals undergoing routine liposuction and was processed by
a 2 step process to obtain only the connective tissue. The tissue was then
evaluated by scanning electronic microscope, Western blot analysis, and flow
cytometry. Results: Liposuctioned fat was obtained from 10 individuals with an
average of 298 mL per subject. After processing an average of 1 mL of collagen
matrix was obtained from each 100 mL of fat. Significant viable cell markers were
present in descending order for adipocytes > CD90+ > CD105+ > CD45+ > CD19+ >
CD144+ > CD34+. Western blot analysis showed collagen type II, III, IV, and other
proteins. Scanning electronic microscope study showed a regular pattern of cross
linked, helical collagen. Additionally, vital staing demonstrated that the cells
were still viable after processing. Conclusions: Collagen and cells can be easily
obtained from liposuctioned fat by ultrasonic separation without alteration of
the overall cellular composition of the tissue. Implantation results in new
collagen and cellular growth. Collagen matrix with viable cells for autologous
use can be obtained from liposuctioned fat and may provide long term results.
Level of Evidence: 5.
PMID- 28510635
TI - Arterial Blood Pressure and Lifestyle Variability: In Quest of a Comprehensive
Approach.
PMID- 28510633
TI - Obesity and Diabetes as Risk Factors for Severe Plasmodium falciparum Malaria:
Results From a Swedish Nationwide Study.
AB - Background: Noncommunicable diseases and obesity are increasing in prevalence
globally, also in populations at risk of malaria. We sought to investigate if
comorbidity, in terms of chronic diseases and obesity, is associated with severe
Plasmodium falciparum malaria. Methods: We performed a retrospective
observational study in adults (>=18 years of age) diagnosed with malaria in
Sweden between January 1995 and May 2015. We identified cases through the
surveillance database at the Public Health Agency of Sweden and reviewed clinical
data from 18 hospitals. Multivariable logistic regression was used to assess
associations between comorbidities and severe malaria. Results: Among 937 adults
(median age, 37 years; 66.5% were male), patients with severe malaria had higher
prevalence of chronic diseases (28/92 [30.4%]) compared with nonsevere cases
(151/845 [17.9%]) (P = .004). Charlson comorbidity score >=1 was associated with
severe malaria (adjusted odds ratio [aOR], 2.63 [95% confidence interval {CI},
1.45-4.77), as was diabetes among individual diagnoses (aOR, 2.98 [95% CI, 1.25
7.09]). Median body mass index was higher among severe (29.3 kg/m2) than
nonsevere cases (24.7 kg/m2) (P < .001). Obesity was strongly associated with
severe malaria, both independently (aOR, 5.58 [95% CI, 2.03-15.36]) and in
combination with an additional metabolic risk factor (hypertension, dyslipidemia,
or diabetes) (aOR, 6.54 [95% CI, 1.87-22.88]). The associations were observed
among nonimmune travelers as well as immigrants from endemic areas. Conclusions:
Comorbidities, specifically obesity and diabetes, are previously unidentified
risk factors for severe malaria in adults diagnosed with P. falciparum.
Noncommunicable diseases should be considered in the acute management and
prevention of malaria.
PMID- 28510637
TI - Telomeres, Nutrition, and Longevity: Can We Really Navigate Our Aging?
AB - Telomeres are dynamic chromosome-end structures that serve as guardians of genome
stability. They are known to be one of the major determinants of aging and
longevity in higher mammals. Studies have demonstrated a direct correlation
between telomere length and life expectancy, stress, DNA damage, and onset of
aging-related diseases. This review discusses the most important factors that
influence our telomeres. Various genetic and environmental factors such as diet,
physical activity, obesity, and stress are known to influence health and
longevity as well as telomere dynamics. Individuals currently have the
opportunity to modulate the dynamics of their aging and health span, monitor
these processes, and even make future projections by following their telomere
dynamics. As telomeres react to positive as well as negative health factors, we
should be able to directly influence our telomere metabolism, slow their
deterioration, and diminish our aging and perhaps extend our life and health
span.
PMID- 28510636
TI - Impact of Aging on Calcium Signaling and Membrane Potential in Endothelium of
Resistance Arteries: A Role for Mitochondria.
AB - Impaired blood flow to peripheral tissues during advanced age is associated with
endothelial dysfunction and diminished bioavailability of nitric oxide (NO).
However, it is unknown whether aging impacts coupling between intracellular
calcium ([Ca2+]i) signaling and small- and intermediate K+ channel (SKCa/IKCa)
activity during endothelium-derived hyperpolarization (EDH), a signaling pathway
integral to dilation of the resistance vasculature. To address the potential
impact of aging on EDH, Fura-2 photometry and intracellular recording were
applied to evaluate [Ca2+]i and membrane potential of intact endothelial tubes
(width, 60 um; length, 1-3 mm) freshly isolated from superior epigastric arteries
of young (4-6 mo) and old (24-26 mo) male C57BL/6 mice. In response to
acetylcholine, intracellular release of Ca2+ from the endoplasmic reticulum (ER)
was enhanced with aging. Further, treatment with the mitochondrial uncoupler FCCP
evoked a significant increase of [Ca2+]i with membrane hyperpolarization in an
SKCa/IKCa-dependent manner in the endothelium of old but not young mice. We
conclude that the ability of resistance artery endothelium to release Ca2+ from
intracellular stores (ie, ER and mitochondria) and hyperpolarize Vm via SKCa/IKCa
activation is augmented as compensation for reduced NO bioavailability during
advanced age.
PMID- 28510638
TI - alpha-Asarone suppresses the proliferation and migration of ASMCs through
targeting the lncRNA-PVT1/miR-203a/E2F3 signal pathway in RSV-infected rats.
AB - Asthma is a chronic inflammatory pulmonary disease and respiratory syncytial
virus (RSV) infection is a common cause of lower respiratory tract illness in
infants and young children. alpha-Asarone presents many pharmacological effects
and has been demonstrated to be useful in treating asthma. However, the
functional mechanism of alpha-asarone in RSV-infected asthma has not been
investigated. Long non-coding RNAs (lncRNAs) have been reported to play critical
roles in many biological processes. Although many lncRNAs have been
characterized, few were reported in asthma, especially in RSV-induced asthma.
Currently, a novel post-transcriptional regulation has been proposed in which
lncRNAs function as competing endogenous RNAs (ceRNAs) to competitively sponge
miRNAs, thereby regulating the target genes. In the present study, we established
an RSV-infected Sprague-Dawley rat model and demonstrated that lncRNA-PVT1 is
involved in the mechanism of alpha-asarone in treating RSV-induced asthma, and
lncRNA-PVT1 regulates the expression of E2F3 by functioning as a ceRNA which
competitively sponges miR-203a.
PMID- 28510640
TI - Increased risk of premature death following teenage abortion and childbirth-a
longitudinal cohort study.
AB - Background: Teenage pregnancy is associated with an increased risk of premature
death. However, it is not known whether the outcome of pregnancy, i.e. induced
abortion or childbirth, affects this risk. Methods: A Finnish population-based
register study involving a cohort of 13 691 nulliparous teenagers who conceived
in 1987-89; 6652 of them underwent induced abortion and 7039 delivered. The
control group consisted of 41 012 coeval women without teenage pregnancy. Follow
up started at the end of pregnancy and lasted until 6th June 2013. Results: Women
with teenage pregnancy had a higher risk of overall mortality vs. controls
(mortality rate ratio [MRR] 1.6, [95% CI 1.4-1.8]) and were more likely to die
prematurely as a result of suicide, alcohol-related causes, circulatory diseases
and motor vehicle accidents. A low educational level appeared to explain these
excess risks, except for suicide (adj. MRR 1.5, [95% CI 1.1-2.0]). After
adjusting for confounders, the childbirth group faced lower risks of suicide
(adj. MRR 0.5, [95% CI 0.3-0.9]) and dying from injury and poisoning (adj. MRR
0.6, [95% CI 0.4-0.8]) compared with women who had undergone abortion.
Conclusions: A low educational level is associated with the increased risk of
premature death among women with a history of teenage pregnancy, except for
suicide. Extra efforts should be made to encourage pregnant teenagers to continue
education, and to provide psychosocial support to teenagers who undergo induced
abortion.
PMID- 28510641
TI - Community-level football injury epidemiology: traumatic injuries treated at
Swedish emergency medical facilities.
AB - Background: Despite the popularity of the sport, few studies have investigated
community-level football injury patterns. This study examines football injuries
treated at emergency medical facilities using data from three Swedish counties.
Methods: An open-cohort design was used based on residents aged 0-59 years in
three Swedish counties (pop. 645 520). Data were collected from emergency medical
facilities in the study counties between 1 January 2007 and 31 December 2010.
Injury frequencies and proportions for age groups stratified by sex were
calculated with 95% confidence intervals (95% CIs) and displayed per diagnostic
group and body location. Results: Each year, more than 1/200 person aged 0-59
years sustained at least one injury during football play that required emergency
medical care. The highest injury incidence was observed among adolescent boys
[2009 injuries per 100 000 population years (95% CI 1914-2108)] and adolescent
girls [1413 injuries per 100 000 population years (95% CI 1333-1498)]. For female
adolescents and adults, knee joint/ligament injury was the outstanding injury
type (20% in ages 13-17 years and 34% in ages 18-29 years). For children aged 7
12 years, more than half of the treated injuries involved the upper extremity;
fractures constituted about one-third of these injuries. Conclusions: One of
every 200 residents aged 0-59 years in typical Swedish counties each year
sustained a traumatic football injury that required treatment in emergency
healthcare. Further research on community-level patterns of overuse syndromes
sustained by participation in football play is warranted.
PMID- 28510639
TI - Toward an elucidation of the molecular genetics of inherited retinal
degenerations.
AB - While individually classed as rare diseases, hereditary retinal degenerations
(IRDs) are the major cause of registered visual handicap in the developed world.
Given their hereditary nature, some degree of intergenic heterogeneity was
expected, with genes segregating in autosomal dominant, recessive, X-linked
recessive, and more rarely in digenic or mitochondrial modes. Today, it is
recognized that IRDs, as a group, represent one of the most genetically diverse
of hereditary conditions - at least 260 genes having been implicated, with 70
genes identified in the most common IRD, retinitis pigmentosa (RP). However,
targeted sequencing studies of exons from known IRD genes have resulted in the
identification of candidate mutations in only approximately 60% of IRD cases.
Given recent advances in the development of gene-based medicines,
characterization of IRD patient cohorts for known IRD genes and elucidation of
the molecular pathologies of disease in those remaining unresolved cases has
become an endeavor of the highest priority. Here, we provide an outline of
progress in this area.
PMID- 28510642
TI - Ageism in Health Care: A Systematic Review of Operational Definitions and
Inductive Conceptualizations.
AB - Purpose: International and national bodies have identified tackling ageism in
health care as an urgent goal. However, health professionals, researchers, and
policy makers recognize that it is not easy to identity and fight ageism in
practice, as the identification of multiple manifestations of ageism is dependent
on the way it is defined and operationalized. This article reports on a
systematic review of the operational definitions and inductive conceptualizations
of ageism in the context of health care. Design and Methods: We reviewed
scientific articles published from January 1995 to June 2015 and indexed in the
electronic databases Web of Science, PubMed, and Cochrane. Electronic searches
were complemented with visual scanning of reference lists and hand searching of
leading journals in the field of ageing and social gerontology. Results: The
review reveals that the predominant forms of operationalization and inductive
conceptualization of ageism in the context of health care have neglected some
components of ageism, namely the self-directed and implicit components.
Furthermore, the instruments used to measure ageism in health care have as
targets older people in general, not older patients in particular. Implications:
The results have important implications for the advancement of research on this
topic, as well as for the development of interventions to fight ageism in
practice. There is a need to take into account underexplored forms of
operationalization and inductive conceptualizations of ageism, such as self
directed ageism and implicit ageism. In addition, ageism in health care should be
measured by using context-specific instruments.
PMID- 28510643
TI - How to Face the Outbreak of Viral Hepatitis A in Men Who Have Sex With Men in
France Without Vaccines?
PMID- 28510644
TI - Temporal trends in acute myocardial infarction presentation and association with
use of cardioprotective drugs: a nationwide registry-based study.
AB - Aim: The present study aimed to investigate temporal trends in myocardial
infarction (MI) presentation with or without ST-segment elevation and the
association with the use of cardioprotective drugs prior to admission. Methods
and results: Using individual-level linkage of data from Danish nationwide
registries, we identified all patients 30 years or older admitted with a first
time MI in the period 2003-2012, and their use of cardioprotective drugs 6 months
prior to admission. We calculated incidence rates per 100 000 person-years (IRs)
of ST-segment elevation MI (STEMI) and non-STEMI (NSTEMI). We identified 22 247
patients admitted with STEMI and 50 403 with NSTEMI. IRs for NSTEMI decreased by
35% from 194 in 2003 to 126 in 2012, whereas IRs for STEMI peaked in 2007 and
subsequently declined from 71 to 65. Preadmission use of cardioprotective drugs
increased in both groups from 2003 to 2012. Patients admitted with STEMI had odds
ratio (OR) 0.64 [95% confidence interval (CI) 0.61-0.67] for preadmission use of
aspirin compared with patients admitted with NSTEMI. Corresponding ORs were 0.82
(CI 0.78-0.87) for statins, 0.87 (CI 0.82-0.91) for beta-blockers, 0.89 (CI 0.85
0.92) for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers,
and 0.52 (CI 0.44-0.61) for thienopyridines. Also, 30-day and 1-year mortality
declined in patients both admitted with STEMI and NSTEMI. Conclusion: The IRs of
MI declined between 2003 and 2012, primarily driven by a 35% reduction in IRs for
NSTEMI whereas IRs for STEMI declined after 2007. Preadmission use of
cardioprotective drugs increased markedly and was associated with lower ORs of
presenting with STEMI than NSTEMI.
PMID- 28510645
TI - Nurse interventions to improve medication adherence among discharged older
adults: a systematic review.
AB - Background: discharged older adult inpatients are often prescribed numerous
medications. However, they only take about half of their medications and many
stop treatments entirely. Nurse interventions could improve medication adherence
among this population. Objective: to conduct a systematic review of trials that
assessed the effects of nursing interventions to improve medication adherence
among discharged, home-dwelling and older adults. Method: we conducted a
systematic review according to the methods in the Cochrane Collaboration Handbook
and reported results according to the PRISMA statement. We searched for
controlled clinical trials (CCTs) and randomised CCTs (RCTs), published up to 8
November 2016 (using electronic databases, grey literature and hand searching),
that evaluated the effects of nurse interventions conducted alone or in
collaboration with other health professionals to improve medication adherence
among discharged older adults. Medication adherence was defined as the extent to
which a patient takes medication as prescribed. Results: out of 1,546 records
identified, 82 full-text papers were evaluated and 14 studies were included-11
RCTs and 2 CCTs. Overall, 2,028 patients were included (995 in intervention
groups; 1,033 in usual-care groups). Interventions were nurse-led in seven
studies and nurse-collaborative in seven more. In nine studies, adherence was
higher in the intervention group than in the usual-care group, with the
difference reaching statistical significance in eight studies. There was no
substantial difference in increased medication adherence whether interventions
were nurse-led or nurse-collaborative. Four of the 14 studies were of relatively
high quality. Conclusion: nurse-led and nurse-collaborative interventions
moderately improved adherence among discharged older adults. There is a need for
large, well-designed studies using highly reliable tools for measuring medication
adherence.
PMID- 28510646
TI - Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the
TOPIC (timing of platelet inhibition after acute coronary syndrome) randomized
study.
AB - Aims: Newer P2Y12 blockers (prasugrel and ticagrelor) demonstrated significant
ischaemic benefit over clopidogrel after acute coronary syndrome (ACS). However,
both drugs are associated with an increase in bleeding complications. The
objective of the present study was to evaluate the benefit of switching dual
antiplatelet therapy (DAPT) from aspirin plus a newer P2Y12 blocker to aspirin
plus clopidogrel 1 month after ACS. Methods and results: We performed an open
label, monocentric, and randomized trial. From March 2014 to April 2016, patients
admitted with ACS requiring coronary intervention, on aspirin and a newer P2Y12
blocker and without adverse event at 1 month, were assigned to switch to aspirin
and clopidogrel (switched DAPT) or continuation of their drug regimen (unchanged
DAPT). The primary outcome was a composite of cardiovascular death, urgent
revascularization, stroke and bleeding as defined by the Bleeding Academic
Research Consortium (BARC) classification >=2 at 1 year post ACS. Six hundred and
forty six patients were randomized and 645 analysed, corresponding to 322
patients in the switched DAPT and 323 in the unchanged DAPT group. The primary
endpoint occurred in 43 (13.4%) patients in the switched DAPT group and in 85
(26.3%) patients in the unchanged DAPT (HR 95%CI 0.48 (0.34-0.68), P < 0.01). No
significant differences were reported on ischaemic endpoints, while BARC >= 2
bleeding occurred in 13 (4.0%) patients in the switched DAPT and in 48 (14.9%) in
the unchanged DAPT group (HR 95%CI 0.30 (0.18-0.50), P < 0.01). Conclusion: A
switched DAPT is superior to an unchanged DAPT strategy to prevent bleeding
complications without increase in ischaemic events following ACS.
PMID- 28510647
TI - Epicardial cardioverter-defibrillator implantation in a 4-month-old infant
bridged to heart transplantation.
AB - Implantable cardioverter-defibrillator (ICD) is the gold standard therapy for the
prevention of sudden cardiac death. Nevertheless, ICD placement in the paediatric
population is still limited because of several technical difficulties. Several
implantation techniques have been proposed but experience in infants with very
low weight and less than 6 months is very limited. We herein describe a case of a
minimally invasive ICD epicardial implantation in a 4-month-old infant weighing 5
kg. A diagnosis of arrhythmic cardiomyopathy with left ventricular non-compaction
disease with ventricular tachycardia storms, QT prolongation and Wolff-Parkinson
White pattern was made. Antiarrhythmic drugs, radiofrequency ablation and
sympathetic denervation were not effective. ICD implantation was successful
allowing the infant to survive and bridging to heart transplantation.
PMID- 28510648
TI - Commentary on: Functional and Volumetric Analysis of the Pectoralis Major Muscle
After Submuscular Breast Augmentation.
PMID- 28510649
TI - The Orbital Septum in Upper Eyelid Retraction and Ptosis Complicating Fat
Injection.
PMID- 28510651
TI - Spotlight on... Jeff Errington.
PMID- 28510650
TI - To Get the Best Outcome, Choose the Best Outcome.
PMID- 28510652
TI - International migrants' use of emergency departments in Europe compared with non
migrants' use: a systematic review.
AB - Background: International migration across Europe is increasing. High rates of
net migration may be expected to increase pressure on healthcare services,
including emergency services. However, the extent to which immigration creates
additional pressure on emergency departments (EDs) is widely debated. This review
synthesizes the evidence relating to international migrants' use of EDs in
European Economic Area (EEA) countries as compared with that of non-migrants.
Methods: MEDLINE, EMBASE, CINAHL, The Cochrane Library and The Web of Science
were searched for the years 2000-16. Studies reporting on ED service utilization
by international immigrants, as compared with non-migrants, were eligible for
inclusion. Included studies were restricted to those conducted in EEA countries
and English language publications only. Results: Twenty-two articles (from six
host countries) were included. Thirteen of 18 articles reported higher volume of
ED service use by immigrants, or some immigrant sub-groups. Migrants were seen to
be significantly more likely to present to the ED during unsocial hours and more
likely than non-migrants to use the ED for low-acuity presentations. Differences
in presenting conditions were seen in 4/7 articles; notably a higher rate of
obstetric and gynaecology presentations among migrant women. Conclusions: The
principal finding of this review is that migrants utilize the ED more, and
differently, to the native populations in EEA countries. The higher use of the ED
for low-acuity presentations and the use of the ED during unsocial hours suggest
that barriers to primary healthcare may be driving the higher use of these
emergency services although further research is needed.
PMID- 28510654
TI - Asn-linked oligosaccharide chain of a crenarchaeon, Pyrobaculum calidifontis, is
reminiscent of the eukaryotic high-mannose-type glycan.
AB - Pyrobaculum calidifontis is a hyperthermophilic archaeon that belongs to the
phylum Crenarchaeota. In contrast to the phylum Euryarchaeota, only the N-glycan
structure of the genus Sulfolobus is known in Crenarchaeota. Here, we enriched
glycoproteins from cultured P. calidifontis cells, by ConA lectin chromatography.
The MASCOT search identified proteins with at least one potential N-glycosylation
site. The MS/MS analysis of twelve small tryptic glycopeptides confirmed the
canonical N-glycosylation consensus in P. calidifontis. We determined the N
linked oligosaccharide structure produced by an in vitro enzymatic oligosaccharyl
transfer reaction. P. calidifontis cells were cultured in rich medium
supplemented with 13C-glucose, for the metabolic labeling of N-oligosaccharide
donors. An incubation with a synthetic peptide substrate produced glycopeptides
with isotopically labeled oligosaccharide moieties. The MS and NMR analysis
revealed that the P. calidifontis N-glycan has a biantennary, high-mannose-type
structure consisting of up to 11 monosaccharide residues. The base portion of the
P. calidifontis N-glycan strongly resembles the eukaryotic core structure, alpha
Man-(1-3)-(alpha-Man-(1-6)-)beta-Man-(1-4)-beta-GlcNAc-(1-4)-beta-GlcNAc-Asn.
Structural differences exist in the anomeric configuration between Man and
GlcNAc, and the chitobiose structure is chemically modified: one GlcNAc residue
is oxidized to glucoronate, and the GlcNAc residues are both modified with an
additional acetamido group at the C-3 position. As a result, the core structure
of the P. calidifontis N-glycan is alpha-Man-(1-3)-(alpha-Man-(1-6)-)alpha-Man-(1
4)-beta-GlcANAc3NAc-(1-4)-beta-GlcNAc3NAc-Asn, in which the unique features of
the P. calidifontis N-glycan are underlined. In spite of these differences, the
structure of the P. calidifontis N-glycan is the most similar to the eukaryotic
counterparts, among all archaeal N- glycans reported to date.
PMID- 28510656
TI - Associations of Environmental Factors With Quality of Life in Older Adults.
AB - Purpose of the Study: Environmental factors play an important role in the quality
of life of older people who often have difficulty maintaining physical,
psychological, and social functioning. In this study, we aimed at (a) developing
a measurement instrument assessing the factors of older adults' perceptions of
their environment, (b) examining the associations of these environmental factors
with quality of life domains physical health, psychological, social relations,
and environmental, controlling for background characteristics. Design and
Methods: Associations between environmental factors and quality of life domains
were examined in a cross-sectional study using a sample of 1,031 Dutch people
aged 65 years and older. Participants completed a Web-based questionnaire, the
"Senioren Barometer." Forty-two questions on environmental factors were asked,
and quality of life domains were assessed by the WHOQOL-BREF. Results: Seven
scales (comprising 3-9 items) of environment were constructed-housing,
facilities, nuisance, residents, neighborhood, stench/noise, and traffic. All
quality of life domains (physical, psychological, social, environmental) were
associated with at least one environmental scale. Housing, residents, and
nuisance were associated with 4, 3, and 2 domains, respectively. Facilities,
neighborhood, stench/noise, and traffic were associated only with quality of life
environmental. Implications: This study showed that multiple environmental
factors are associated with quality of life in older people. To support
independent living in older people health and social care professionals and
policymakers may need to carry out interventions, in particular focusing on
housing, residents, and nuisance.
PMID- 28510653
TI - Chronic Corticosterone Treatment During Adolescence Has Significant Effects on
Metabolism and Skeletal Development in Male C57BL6/N Mice.
AB - Glucocorticoids are potent modulators of metabolic and behavioral function. Their
role as mediators in the "stress response" is well known, but arguably their
primary physiological function is in the regulation of cellular and organismal
metabolism. Disruption of normal glucocorticoid function is linked to metabolic
disease, such as Cushing syndrome. Glucocorticoids are also elevated in many
forms of obesity, suggesting that there are bidirectional effects of these potent
hormones on metabolism and metabolic function. Adolescence is a time of rapid
physical growth, and disruptions during this critical time likely have important
implications for adult function. The hypothalamic-pituitary-adrenal axis
continues to mature during this period, as do tissues that respond to
glucocorticoids. In this work, we investigate how chronic noninvasive exposure to
corticosterone affects metabolic outcomes (body weight, body composition,
insulin, and glucose homeostasis), as well as changes in bone density in both
adult and adolescent male mice. Specifically, we report a different pattern of
metabolic effects in adolescent mice compared with adults, as well as an altered
trajectory of recovery in adolescents and adults. Together, these data indicate
the profound influence that adolescent development has on the metabolic outcomes
of chronic corticosterone exposure, and describe a tractable model for
understanding the short- and long-term impacts of hypercortisolemic states on
physiological and neurobehavioral functions.
PMID- 28510655
TI - miR-145 promoted anoikis resistance in tumor endothelial cells.
AB - Tumor progression is dependent on tumor angiogenesis. We previously reported that
the phenotype of tumor endothelial cells (TECs) is distinct from normal
endothelial cells (NECs). Herein, we conducted a pathway analysis using a public
TEC microarray database and identified several putative TEC-specific miRNAs. We
found that miR-145 expression was upregulated in TECs and that miR-145 enhanced
cell adhesion and anoikis resistance and upregulated Bcl-2 and Bcl-xl via ERK1/2
in human microvascular endothelial cells. These findings suggested that miR-145
is involved in the acquisition of the TEC phenotype, partially. Therefore, miR
145 and its target genes may be molecular targets for anti-angiogenic therapy.
PMID- 28510657
TI - Heteroblasty in epiphytic bromeliads: functional implications for species in
understorey and exposed growing sites.
AB - Background and Aims: The functional relevance of heteroblasty, an abrupt
morphological change in the ontogeny of a considerable number of angiosperm
species, is still largely unresolved. During the ontogeny of many epiphytic
Tillandsioids (Bromeliaceae), such a change occurs when small individuals
transform into larger, tank-forming individuals that are capable of external
water storage. Apart from its fundamental effect on plant water relations, the
associated transition from narrow to broader leaves also affects plant
architecture. The morphological changes and their effect on light interception
may be especially relevant for heteroblastic species in the moist understorey,
which are expected to be limited primarily by light. Methods: A functional
structural plant model (Yplant) was used to construct digital replicas of
atmospheric and tank-forming individuals of four species, two of them naturally
growing in exposed conditions and two occurring in understorey sites. This
allowed the determination of leaf display efficiencies as well as a systematic
analysis of leaf architectural traits and their effect on light interception. Key
Results: Modifying existing plant morphologies showed that broader leaves cause
more self-shading within the plant. This supports the hypothesis that species
from the light-limited understorey benefit from the early atmospheric life form
through increased light capture. Modelling plant morphology that continuously
followed the ontogenetic trajectories of the leaf architectural traits revealed
that the rising total leaf number in atmospheric individuals constantly increased
self-shading. Therefore, at a certain ontogenetic stage, a tipping point was
reached when the tank form was even favourable in terms of light capture as it
was associated with fewer leaves. Conclusions: The effects of changes in leaf
morphology and leaf architecture on plant light capture may explain the common
occurrence of heteroblastic species in the understorey of Neotropical forests,
which does not negate a simultaneous positive effect of heteroblasty on plant
water relations.
PMID- 28510659
TI - Omission in Text.
PMID- 28510658
TI - Data Error.
PMID- 28510661
TI - Tardive Dyskinesia Drug Approved.
PMID- 28510660
TI - Cardiovascular Mortality Differences-Place Matters.
PMID- 28510662
TI - Digitized Surgical Slides.
PMID- 28510663
TI - A First in HCV Drugs for Youths.
PMID- 28510664
TI - Trends in Use of Sedation for Low-Risk Endoscopy: Looking Beyond Monitored
Anesthesia Care.
PMID- 28510665
TI - Antithrombotic Therapy for Venous Thromboembolic Disease.
PMID- 28510667
TI - Hunger, Health, and Compassion.
PMID- 28510668
TI - The Supply of Doctors.
PMID- 28510669
TI - Postoperative Opioid Prescribing and the Pain Scores on Hospital Consumer
Assessment of Healthcare Providers and Systems Survey.
PMID- 28510671
TI - Global Burden of Disease Attributable to Hypertension.
PMID- 28510670
TI - Associations Between Hospital Characteristics, Measure Reporting, and the Centers
for Medicare & Medicaid Services Overall Hospital Quality Star Ratings.
PMID- 28510672
TI - Intubation During In-Hospital Cardiac Arrest.
PMID- 28510673
TI - Legal Ramifications of Ambiguous Clinical Guidelines.
PMID- 28510674
TI - Global Burden of Disease Attributable to Hypertension-Reply.
PMID- 28510675
TI - Intubation During In-Hospital Cardiac Arrest-Reply.
PMID- 28510676
TI - Legal Ramifications of Ambiguous Clinical Guidelines-Reply.
PMID- 28510677
TI - Drugs for Head Lice.
PMID- 28510678
TI - Trends and Patterns of Geographic Variation in Cardiovascular Mortality Among US
Counties, 1980-2014.
AB - Importance: In the United States, regional variation in cardiovascular mortality
is well-known but county-level estimates for all major cardiovascular conditions
have not been produced. Objective: To estimate age-standardized mortality rates
from cardiovascular diseases by county. Design and Setting: Deidentified death
records from the National Center for Health Statistics and population counts from
the US Census Bureau, the National Center for Health Statistics, and the Human
Mortality Database from 1980 through 2014 were used. Validated small area
estimation models were used to estimate county-level mortality rates from all
cardiovascular diseases, including ischemic heart disease, cerebrovascular
disease, ischemic stroke, hemorrhagic stroke, hypertensive heart disease,
cardiomyopathy, atrial fibrillation and flutter, rheumatic heart disease, aortic
aneurysm, peripheral arterial disease, endocarditis, and all other cardiovascular
diseases combined. Exposures: The 3110 counties of residence. Main Outcomes and
Measures: Age-standardized cardiovascular disease mortality rates by county,
year, sex, and cause. Results: From 1980 to 2014, cardiovascular diseases were
the leading cause of death in the United States, although the mortality rate
declined from 507.4 deaths per 100 000 persons in 1980 to 252.7 deaths per 100
000 persons in 2014, a relative decline of 50.2% (95% uncertainty interval [UI],
49.5%-50.8%). In 2014, cardiovascular diseases accounted for more than 846 000
deaths (95% UI, 827-865 thousand deaths) and 11.7 million years of life lost (95%
UI, 11.6-11.9 million years of life lost). The gap in age-standardized
cardiovascular disease mortality rates between counties at the 10th and 90th
percentile declined 14.6% from 172.1 deaths per 100 000 persons in 1980 to 147.0
deaths per 100 000 persons in 2014 (posterior probability of decline >99.9%). In
2014, the ratio between counties at the 90th and 10th percentile was 2.0 for
ischemic heart disease (119.1 vs 235.7 deaths per 100 000 persons) and 1.7 for
cerebrovascular disease (40.3 vs 68.1 deaths per 100 000 persons). For other
cardiovascular disease causes, the ratio ranged from 1.4 (aortic aneurysm: 3.5 vs
5.1 deaths per 100 000 persons) to 4.2 (hypertensive heart disease: 4.3 vs 17.9
deaths per 100 000 persons). The largest concentration of counties with high
cardiovascular disease mortality extended from southeastern Oklahoma along the
Mississippi River Valley to eastern Kentucky. Several cardiovascular disease
conditions were clustered substantially outside the South, including atrial
fibrillation (Northwest), aortic aneurysm (Midwest), and endocarditis (Mountain
West and Alaska). The lowest cardiovascular mortality rates were found in the
counties surrounding San Francisco, California, central Colorado, northern
Nebraska, central Minnesota, northeastern Virginia, and southern Florida.
Conclusions and Relevance: Substantial differences exist between county ischemic
heart disease and stroke mortality rates. Smaller differences exist for diseases
of the myocardium, atrial fibrillation, aortic and peripheral arterial disease,
rheumatic heart disease, and endocarditis.
PMID- 28510679
TI - Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and
Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial.
AB - Importance: Synovitis is common and is associated with progression of structural
characteristics of knee osteoarthritis. Intra-articular corticosteroids could
reduce cartilage damage associated with synovitis but might have adverse effects
on cartilage and periarticular bone. Objective: To determine the effects of intra
articular injection of 40 mg of triamcinolone acetonide every 3 months on
progression of cartilage loss and knee pain. Design, Setting, and Participants:
Two-year, randomized, placebo-controlled, double-blind trial of intra-articular
triamcinolone vs saline for symptomatic knee osteoarthritis with ultrasonic
features of synovitis in 140 patients. Mixed-effects regression models with a
random intercept were used to analyze the longitudinal repeated outcome measures.
Patients fulfilling the American College of Rheumatology criteria for symptomatic
knee osteoarthritis, Kellgren-Lawrence grades 2 or 3, were enrolled at Tufts
Medical Center beginning February 11, 2013; all patients completed the study by
January 1, 2015. Interventions: Intra-articular triamcinolone (n = 70) or saline
(n = 70) every 12 weeks for 2 years. Main Outcomes and Measures: Annual knee
magnetic resonance imaging for quantitative evaluation of cartilage volume
(minimal clinically important difference not yet defined), and Western Ontario
and McMaster Universities Osteoarthritis index collected every 3 months (Likert
pain subscale range, 0 [no pain] to 20 [extreme pain]; minimal clinically
important improvement, 3.94). Results: Among 140 randomized patients (mean age,
58 [SD, 8] years, 75 women [54%]), 119 (85%) completed the study. Intra-articular
triamcinolone resulted in significantly greater cartilage volume loss than did
saline for a mean change in index compartment cartilage thickness of -0.21 mm vs
0.10 mm (between-group difference, -0.11 mm; 95% CI, -0.20 to -0.03 mm); and no
significant difference in pain (-1.2 vs -1.9; between-group difference, -0.6; 95%
CI, -1.6 to 0.3). The saline group had 3 treatment-related adverse events
compared with 5 in the triamcinolone group and had a small increase in hemoglobin
A1c levels (between-group difference, -0.2%; 95% CI, -0.5% to -0.007%).
Conclusions and Relevance: Among patients with symptomatic knee osteoarthritis, 2
years of intra-articular triamcinolone, compared with intra-articular saline,
resulted in significantly greater cartilage volume loss and no significant
difference in knee pain. These findings do not support this treatment for
patients with symptomatic knee osteoarthritis. Trial Registration:
ClinicalTrials.gov Identifier: NCT01230424.
PMID- 28510681
TI - Reducing Risk of Dementia in Older Age.
PMID- 28510683
TI - Determination.
PMID- 28510685
TI - Scarcity of Safe Water a Looming Threat to Children.
PMID- 28510680
TI - Effect of Oral Iron Repletion on Exercise Capacity in Patients With Heart Failure
With Reduced Ejection Fraction and Iron Deficiency: The IRONOUT HF Randomized
Clinical Trial.
AB - Importance: Iron deficiency is present in approximately 50% of patients with
heart failure with reduced left ventricular ejection fraction (HFrEF) and is an
independent predictor of reduced functional capacity and mortality. However, the
efficacy of inexpensive readily available oral iron supplementation in heart
failure is unknown. Objective: To test whether therapy with oral iron improves
peak exercise capacity in patients with HFrEF and iron deficiency. Design,
Setting, and Participants: Phase 2, double-blind, placebo-controlled randomized
clinical trial of patients with HFrEF (<40%) and iron deficiency, defined as a
serum ferritin level of 15 to 100 ng/mL or a serum ferritin level of 101 to 299
ng/mL with transferrin saturation of less than 20%. Participants were enrolled
between September 2014 and November 2015 at 23 US sites. Interventions: Oral iron
polysaccharide (n = 111) or placebo (n = 114), 150 mg twice daily for 16 weeks.
Main Outcomes and Measures: The primary end point was a change in peak oxygen
uptake (Vo2) from baseline to 16 weeks. Secondary end points were change in 6
minute walk distance, plasma N-terminal pro-B-type natriuretic peptide (NT
proBNP) levels, and health status as assessed by Kansas City Cardiomyopathy
Questionnaire (KCCQ, range 0-100, higher scores reflect better quality of life).
Results: Among 225 randomized participants (median age, 63 years; 36% women) 203
completed the study. The median baseline peak Vo2 was 1196 mL/min (interquartile
range [IQR], 887-1448 mL/min) in the oral iron group and 1167 mL/min (IQR, 887
1449 mL/min) in the placebo group. The primary end point, change in peak Vo2 at
16 weeks, did not significantly differ between the oral iron and placebo groups
(+23 mL/min vs -2 mL/min; difference, 21 mL/min [95% CI, -34 to +76 mL/min]; P =
.46). Similarly, at 16 weeks, there were no significant differences between
treatment groups in changes in 6-minute walk distance (-13 m; 95% CI, -32 to 6
m), NT-proBNP levels (159; 95% CI, -280 to 599 pg/mL), or KCCQ score (1; 95% CI,
2.4 to 4.4), all P > .05. Conclusions and Relevance: Among participants with
HFrEF with iron deficiency, high-dose oral iron did not improve exercise capacity
over 16 weeks. These results do not support use of oral iron supplementation in
patients with HFrEF. Trial Registration: clinicaltrials.gov Identifier:
NCT02188784.
PMID- 28510687
TI - Massive Polio Vaccination Drive in African Nations.
PMID- 28510686
TI - Freeze-dried Rotavirus Vaccine Shows Promise.
PMID- 28510690
TI - Trichosporonosis in Pediatric Patients With a Hematologic Disorder.
AB - Background: Trichosporonosis is an emerging and often fatal opportunistic fungal
infection in immunocompromised patients, particularly those with hematologic
malignancy, but data in children are lacking. Methods: We report here 3 cases of
invasive infection caused by Trichosporon asahii in pediatric patients with acute
lymphoblastic leukemia at Texas Children's Hospital in Houston, Texas. We also
conducted a literature review and identified 16 additional reports of pediatric
patients with invasive T asahii infection and an underlying malignant or
nonmalignant hematologic disorder. Results: Of the 19 cases of invasive T asahii
infection, the most commonly reported underlying hematologic disorder was acute
lymphoblastic leukenia (47%), followed by acute myelogenous leukemia (21%). Most
of the patients (94%) had neutropenia, defined as an absolute neutrophil count of
<500 cells/mm3. Antifungal prophylaxis information was available in 6 of the 19
cases, and micafungin use was reported in 5 cases. Treatment regimens frequently
included voriconazole monotherapy (47%) or the combination of an azole antifungal
with amphotericin B (35%). The mortality rate was 58%. Conclusions: Recognizing
that echinocandins, which are increasingly used for prophylaxis in patients with
a hematologic malignancy, are not active against Trichosporon species is of
critical importance. The recommended first-line therapy for trichosporonosis is
voriconazole, but successful outcome depends largely on the underlying immune
status of the host.
PMID- 28510689
TI - Chronic Enteropathy Associated With SLCO2A1 Gene [CEAS]-Characterisation of an
Enteric Disorder to be Considered in the Differential Diagnosis of Crohn's
Disease.
AB - Small intestinal ulcers include mucosal damage caused by drugs, particularly
nonsteroidal anti-inflammatory drugs [NSAIDs], infectious diseases, and
idiopathic inflammatory bowel disease. Previously, a group of Japanese
investigators reported an unusual and uncommon type of enteritis and referred to
the condition as chronic nonspecific multiple ulcers of the small intestine
[CNSU]. CNSU is characterised by chronic blood and protein loss through
persistent small intestinal ulcers. Recently, four candidate mutations in the
solute carrier organic anion transporter family, member 2A1 [SLCO2A1] gene,
encoding a prostaglandin transporter, were identified by whole-exome sequencing
in patients with CNSU. However, because the name 'CNSU' was somewhat ambiguous,
the more appropriate nomenclature of 'chronic enteropathy associated with the
SLCO2A1 gene' [CEAS] has been suggested. CEAS ulcers are characterised by
multiple, circular or eccentric oblique, shallow lesions with discrete margins.
The most frequently affected site of CEAS is the ileum, in contrast to
'cryptogenic multifocal ulcerous stenosing enteritis [CMUSE]', for which the most
frequent site is the jejunum. Impaired prostaglandin utilisation is thought to
cause the small intestinal mucosal damage observed in CEAS, CMUSE, and NSAID
induced enteropathy. This review article focuses on endoscopic and clinical
features of genetically diagnosed CEAS, accumulated in a nationwide survey, and
illustrates the observations in the format of an atlas.
PMID- 28510692
TI - Disseminated Neonatal Herpes Simplex Virus Type 1 After a Water Birth.
AB - Neonatal herpes simplex virus (NHSV) infections are associated with significant
morbidity and mortality. Numerous factors influence the transmission of HSV
infection to newborns; however, immersion in water during labor has received very
little attention as a possible risk factor despite the increasing popularity of
water births. We report a case of disseminated NHSV type 1 infection, possibly
acquired during a water birth. The purpose of this report is to alert healthcare
providers to this potential route of transmission and to highlight the importance
of screening guidelines for HSV before a water birth. Furthermore, it is
essential to consider NHSV infection in any febrile infant who is not responding
to standard empirical antibiotic management, even in the absence of herpetic
lesions.
PMID- 28510691
TI - NF-kappaB upregulation through epigenetic silencing of LDOC1 drives tumor biology
and specific immunophenotype in Group A ependymoma.
AB - Background: Inflammation has been identified as a hallmark of high-risk Group A
(GpA) ependymoma (EPN). Chronic interleukin (IL)-6 secretion from GpA tumors
drives an immune suppressive phenotype by polarizing infiltrating monocytes. This
study determines the mechanism by which IL-6 is dysregulated in GpA EPN. Methods:
Twenty pediatric GpA and 21 pediatric Group B (GpB) EPN had gene set enrichment
analysis for MSigDB Hallmark gene sets performed. Protein and RNA from patients
and cell lines were used to validate transcriptomic findings. GpA cell lines 811
and 928 were used for in vitro experiments performed in this study. Results: The
nuclear factor-kappaB (NF-kappaB) pathway is a master regulator of IL-6 and a
signaling pathway enriched in GpA compared with GpB EPN. Knockdown of NF-kappaB
led to significant downregulation of IL-6 in 811 and 928. NF-kappaB activation
was independent of tumor necrosis factor alpha (TNF-alpha) stimulation in both
cell lines, suggesting that NF-kappaB hyperactivation is mediated through an
alternative mechanism. Leucine zipper downregulated in cancer 1 (LDOC1) is a
known transcriptional repressor of NF-kappaB. In many cancers, LDOC1 promoter is
methylated, which inhibits gene transcription. We found decreased LDOC1 gene
expression in GpA compared with GpB EPN, and in other pediatric brain tumors. EPN
cells treated with 5AZA-DC, demethylated LDOC1 regulatory regions, upregulated
LDOC1 expression, and concomitantly decreased IL-6 secretion. Stable knockdown of
LDOC1 in EPN cell lines resulted in a significant increase in gene transcription
of v-rel avian reticuloendotheliosis viral oncogene homolog A, which correlated
to an increase in NF-kappaB target genes. Conclusion: These results suggest that
epigenetic silencing of LDOC1 in GpA EPN regulates tumor biology and drives
inflammatory immune phenotype.
PMID- 28510694
TI - Exploring the interrelationship between sport, health and social outcomes in the
UK: implications for health policy.
AB - Background: Policy agencies are now re-visiting early aspirations that sport, as
a form of physical activity, can be an instrument to foster general health and
also subjective well-being (SWB). Both of these concepts capture physical and
mental health states. SWB also encompasses broader psychological and life
satisfaction as well as mood and affect. Past and current policies also identify
a link between sport, social capital and SWB. Methods: Structural Equation
Modelling (SEM) is undertaken on data from the UK's Taking Part survey to
investigate the interrelationships between sport, general health, social capital
and SWB. Results: The SEM shows a simultaneous relationship between sport and
SWB. The effect is mediated through general health. The results also show that
there is no relationship between social capital and sport but a clear
relationship between SWB and social capital. Conclusions: From a health policy
perspective there should be an emphasis on encouraging greater sport
participation, despite the difficulties that this poses, because there is a
potential 'multiplier' effect on SWB and on general health through mediation. The
multiplier effect occurs because once someone engages in sport and has their
general health and SWB enhanced, then even further sport participation becomes
likely, and subsequent general health and SWB, which would comprise both physical
and mental health benefits. To target traditional non participants the research
suggests that physical activity should be promoted for enjoyment, with health
benefits subsequently following.
PMID- 28510693
TI - Sputum Microscopy With Fluorescein Diacetate Predicts Tuberculosis
Infectiousness.
AB - Background: Sputum from patients with tuberculosis contains subpopulations of
metabolically active and inactive Mycobacterium tuberculosis with unknown
implications for infectiousness. Methods: We assessed sputum microscopy with
fluorescein diacetate (FDA, evaluating M. tuberculosis metabolic activity) for
predicting infectiousness. Mycobacterium tuberculosis was quantified in
pretreatment sputum of patients with pulmonary tuberculosis using FDA microscopy,
culture, and acid-fast microscopy. These 35 patients' 209 household contacts were
followed with prevalence surveys for tuberculosis disease for 6 years. Results:
FDA microscopy was positive for a median of 119 (interquartile range [IQR], 47
386) bacteria/uL sputum, which was 5.1% (IQR, 2.4%-11%) the concentration of acid
fast microscopy-positive bacteria (2069 [IQR, 1358-3734] bacteria/MUL).
Tuberculosis was diagnosed during follow-up in 6.4% (13/209) of contacts. For
patients with lower than median concentration of FDA microscopy-positive M.
tuberculosis, 10% of their contacts developed tuberculosis. This was
significantly more than 2.7% of the contacts of patients with higher than median
FDA microscopy results (crude hazard ratio [HR], 3.8; P = .03). This association
maintained statistical significance after adjusting for disease severity,
chemoprophylaxis, drug resistance, and social determinants (adjusted HR, 3.9; P =
.02). Conclusions: Mycobacterium tuberculosis that was FDA microscopy negative
was paradoxically associated with greater infectiousness. FDA microscopy-negative
bacteria in these pretreatment samples may be a nonstaining, slowly metabolizing
phenotype better adapted to airborne transmission.
PMID- 28510688
TI - Two-component systems required for virulence in Pseudomonas aeruginosa.
AB - Pseudomonas aeruginosa is a versatile opportunistic pathogen capable of infecting
a broad range of hosts, in addition to thriving in a broad range of environmental
conditions outside of hosts. With this versatility comes the need to tightly
regulate its genome to optimise its gene expression and behaviour to the
prevailing conditions. Two-component systems (TCSs) comprising sensor kinases and
response regulators play a major role in this regulation. This minireview
discusses the growing number of TCSs that have been implicated in the virulence
of P. aeruginosa, with a special focus on the emerging theme of multikinase
networks, which are networks comprising multiple sensor kinases working together,
sensing and integrating multiple signals to decide upon the best response. The
networks covered in depth regulate processes such as the switch between acute and
chronic virulence (GacS network), the Cup fimbriae (Roc network and Rcs/Pvr
network), the aminoarabinose modification of lipopolysaccharide (a network
involving the PhoQP and PmrBA TCSs), twitching motility and virulence (a network
formed from the Chp chemosensory pathway and the FimS/AlgR TCS), and biofilm
formation (Wsp chemosensory pathway). In addition, we highlight the important
interfaces between these systems and secondary messenger signals such as cAMP and
c-di-GMP.
PMID- 28510695
TI - Effects of an autoinducer analogue on antibiotic tolerance in Pseudomonas
aeruginosa.
AB - Objectives: Antibiotic tolerance causes chronic, refractory and persistent
infections. In order to advance the development of a new type of drug for the
treatment of infectious diseases, we herein investigated the effects of a newly
synthesized analogue of the Pseudomonas aeruginosa quorum-sensing autoinducer
named AIA-1 ( a uto i nducer a nalogue) on antibiotic tolerance in P. aeruginosa
. Methods: A P. aeruginosa luminescent strain derived from PAO1 was injected into
neutropenic ICR mice and bioluminescence images were acquired for a period of
time after treatments with antibiotics and AIA-1. In vitro susceptibility testing
and killing assays for the planktonic and biofilm cells of PAO1 were performed
using antibiotics and AIA-1. The expression of quorum-sensing-related genes was
examined using real-time PCR. Results: In vivo and in vitro assays showed that
AIA-1 alone did not exert any bactericidal effects and also did not affect the
MICs of antibiotics. However, the combined use of AIA-1 and antibiotics exerted
markedly stronger therapeutic effects against experimental infection than
antibiotics alone. The presence of AIA-1 also enhanced the killing effects of
antibiotics in planktonic and biofilm cells. Although AIA-1 did not inhibit the
expression of lasB and rhlA genes, which are directly regulated by quorum
sensing, it clearly suppressed expression of the rpoS gene. Conclusions: The new
compound, AIA-1, did not alter the antibiotic susceptibility of P. aeruginosa by
itself; however, its addition enhanced the antibacterial activity of antibiotics.
AIA-1 did not inhibit quorum sensing, but reduced the antibiotic tolerance of P.
aeruginosa by suppressing rpoS gene expression.
PMID- 28510696
TI - Autologous Adipose-Derived Tissue Matrix Part II: Implantation Biology.
AB - Background: In part 1 of this study it was shown that liposuctioned fat could be
a sufficient source of autologous collagen for use as a filler or in
reconstruction. The collagen composition in liposuctioned fat was shown to form a
cross-linked helical matrix composed of types II, III, and IV. Additionally,
viable adipocytes and fibroblasts among other cells were found. Objectives: The
purpose of this research was to study the biology of this matrix after subsequent
implantation compared to Juvederm (Allergan, Parsippany, NJ) common soft tissue
filler. Methods: Fat was obtained from individuals undergoing routine liposuction
and was processed by a two-step process to obtain a connective tissue matrix. The
matrix was then cryo-frozen for a minimum of 4 weeks after which it was thawed
and implanted in 46 nude mice. Juvederm Ultra was used as the control article and
the animals followed for one year. Results: Liposuctioned fat was obtained from
10 individuals and processed as previously described. Mice were harvested at 3,
6, 9, and 12 months and histology obtained. There were no adverse effects from
either article and the bio-reactivity rating was 0. The implanted collagen
compared favorably to Juvederm at all stages and was found to be replaced by new
collagen and fat. Conclusions: A collagen matrix with viable cells for autologous
use can be obtained from liposuctioned fat which has been processed and cryo
frozen. The material lasts at least one year and is slowly replaced by new
collagenand fat. Level of Evidence: 5.
PMID- 28510698
TI - XSuLT: a web server for structural annotation and representation of sequence
structure alignments.
AB - The web server XSuLT, an enhanced version of the protein alignment annotation
program JoY, formats a submitted multiple-sequence alignment using three
dimensional (3D) structural information in order to assist in the comparative
analysis of protein evolution and in the optimization of alignments for
comparative modelling and construct design. In addition to the features analysed
by JoY, which include secondary structure, solvent accessibility and sidechain
hydrogen bonds, XSuLT annotates each amino acid residue with residue depth, chain
and ligand interactions, inter-residue contacts, sequence entropy, root mean
square deviation and secondary structure and disorder prediction. It is also now
integrated with built-in 3D visualization which interacts with the formatted
alignment to facilitate inspection and understanding. Results can be downloaded
as stand-alone HTML for the formatted alignment and as XML with the underlying
annotation data. XSuLT is freely available at
http://structure.bioc.cam.ac.uk/xsult/.
PMID- 28510699
TI - Invasive Pneumococcal Disease in Infants Aged 0-60 Days in the United States in
the 13-Valent Pneumococcal Conjugate Vaccine Era.
AB - We identified 53 infants aged 0-60 days with invasive pneumococcal disease (IPD)
at 8 children's hospitals in the United States (2005-2015). After the
introduction of 13-valent pneumococcal conjugate vaccine (PCV13), IPD caused by
PCV13 serotypes decreased ~30% providing some evidence of indirect protection.
However, approximately 60% of IPD was still caused by PCV13 serotypes.
PMID- 28510701
TI - Sputum Microscopy and Mycobacterium tuberculosis Infectiousness.
PMID- 28510697
TI - BCCIPbeta modulates the ribosomal and extraribosomal function of S7 through a
direct interaction.
AB - Extraribosomal functions of ribosomal proteins (RPs) have gained much attention
for their implications in tumorigenesis and progression. However, the regulations
for transition between the ribosomal and extraribosomal functions of RPs are
rarely reported. Herein, we identified a ribosomal protein S7-interacting
partner, BCCIPbeta, which modulates the functional conversion of S7. Through the
N-terminal acidic domain, BCCIPbeta interacts with the central basic region in S7
and regulates the extraribosomal distribution of S7. BCCIPbeta deficiency
abrogates the ribosomal accumulation but enhances the ribosome-free location of
S7. This translocation further impairs protein synthesis and triggers ribosomal
stress. Consequently, BCCIPbeta deficiency suppresses the ribosomal function and
initiates the extraribosomal function of S7, resulting in restriction of cell
proliferation. Moreover, clinically relevant S7 mutations were found to dampen
the interaction with BCCIPbeta and facilitate the functional transition of S7. In
conclusion, BCCIPbeta, as a S7 modulator, contributes to the regulation of
ribosomal and extraribosomal functions of S7 and has implications in cell growth
and tumor development.
PMID- 28510700
TI - Enhanced biological activities of gamma-irradiated persimmon leaf extract.
AB - The aim of this study was to compare the anti-oxidative and anti-inflammatory
activities of gamma-irradiated persimmon leaf extract (GPLE) with those of non
irradiated persimmon leaf extract (PLE). Ethanolic extract of persimmon leaf was
exposed to gamma irradiation at a dose of 10 kGy. After gamma irradiation, the
color of the extract changed from dark brown to light brown. The anti-oxidative
and anti-inflammatory activities of GPLE and PLE were assessed from: total
polyphenol and total flavonoid contents; 2,2-diphenyl-1-picrylhydrazyl (DPPH)
assay; 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assay, and
levels of pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E2
(PGE2), tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). The
total polyphenol contents of GPLE and PLE were determined to be 224.44 +/- 1.54
and 197.33 +/- 5.81 mg gallic acid equivalents (GAE)/g, respectively, and the
total flavonoid contents of GPLE and PLE were 206.27 +/- 1.15 and 167.60 +/- 2.00
mg quercetin equivalents (QUE)/g, respectively. The anti-oxidant activities of
GPLE and PLE as measured by DPPH assays were 338.33 +/- 30.19 MUg/ml (IC50) and
388.68 +/- 8.45 MUg/ml (IC50), respectively, and those measured by ABTS assays
were 510.49 +/- 15.12 MUg/ml (IC50) and 731.30 +/- 10.63 MUg/ml (IC50),
respectively. IC50 is the inhibitor concentration that reduces the response by
50%. GPLE strongly inhibited the production of NO, PGE2 and IL-6 compared with
PLE in lipopolysaccharide-stimulated RAW264.7 macrophages. Furthermore, GPLE
significantly inhibited the production of TNF-alpha and IL-6 cytokines compared
with PLE in phorbol 12-myristate 13-acetate (PMA) plus A23187-stimulated HMC-1
human mast cells. These results indicate that gamma irradiation of PLE can
enhance its anti-oxidative and anti-inflammatory activities through elevation of
the phenolic contents. Therefore, gamma-irradiated PLE has potential for use in
the food and cosmetic industries.
PMID- 28510702
TI - Linking Vegetation Structure and Spider Diversity in Riparian and Adjacent
Habitats in Two Rivers of Central Argentina: An Analysis at Two Conceptual
Levels.
AB - The link between vegetation structure and spider diversity has been well explored
in the literature. However, few studies have compared spider diversity and its
response to vegetation at two conceptual levels: assemblage (species diversity)
and ensemble (guild diversity). Because of this, we studied spider diversity in
riparian and adjacent habitats of a river system from the Chacoan subregion in
central Argentina and evaluated their linkage with vegetation structure at these
two levels. To assess vegetation structure, we measured plant species richness
and vegetation cover in the herb and shrub - tree layers. We collected spiders
for over 6 months by using vacuum netting, sweep netting and pitfall traps. We
collected 3,808 spiders belonging to 119 morphospecies, 24 families and 9 guilds.
At spider assemblage level, SIMPROF analysis showed significant differences among
studied habitats. At spider ensemble level, nevertheless, we found no significant
differences among habitats. Concerning the linkage with vegetation structure,
BIOENV test showed that spider diversity at either assemblage or ensemble level
was not significantly correlated with the vegetation variables assessed. Our
results indicated that spider diversity was not affected by vegetation structure.
Hence, even though we found a pattern in spider assemblages among habitats, this
could not be attributed to vegetation structure. In this study, we show that
analyzing a community at two conceptual levels will be useful for recognizing
different responses of spider communities to vegetation structure in diverse
habitat types.
PMID- 28510704
TI - Skin Disorders in Egyptian Children with beta-Thalassemia Major.
AB - Background: Thalassemia major is one of the common genetic disorders in Egypt.
Skin disorders are usually neglected and frequently underdiagnosed among these
patients. Objective: This work aimed to study the frequency and pattern of skin
manifestations in Egyptian children with beta-thalassemia. Methods: Fifty-four
beta-thalassemia major patients being followed at the Hematology Clinic of Beni
Suef University Hospital were selected to participate in this study. All patients
underwent detailed history evaluation, clinical examination and laboratory
investigations, including complete blood count and serum ferritin. All patients
were examined by a dermatologist to record any skin disorders. Results: Pruritus
(37%), scars (33.3%), hyperpigmentation (31.5%) and xerosis (22.2%) were the most
common findings. We found significant relations between serum ferritin and the
occurrence of scars, hyperpigmentation, xerosis and ephelides (p <0.05). Also,
significant associations between use of deferoxamine and scars (p=0.004),
hyperpigmentation (p=0.004), xerosis (p=0.03) and ephelides (p=0.042) were found.
Conclusion: Skin disorders are frequent in Egyptian children with thalassemia
major. Careful skin examination is required to provide early diagnosis.
PMID- 28510703
TI - Long-chain fatty acid triglyceride (TG) metabolism disorder impairs male
fertility: a study using adipose triglyceride lipase deficient mice.
AB - STUDY QUESTION: Does the deletion of adipose triglyceride lipase (Atgl) gene
impair male fertility? SUMMARY ANSWER: The deletion of Atgl gene impaired male
fertility but the effect was partially reversed by a low long-chain triglyceride
(TG) diet. WHAT IS KNOWN ALREADY: ATGL specifically hydrolyses long-chain fatty
acid TG to diacylglycerol and a high level of expression of ATGL in testes has
been reported. However, the role of ATGL in male fertility is unknown. STUDY
DESIGN, SIZE, DURATION: To investigate the effect of deletion of Atgl gene on
male fertility, cauda epididymides and testes were collected from wild-type,
heterozygous and homozygous Atgl-deficient mice at 10 weeks of age and epididymal
sperm analysis and histological analysis of the testes were performed. To
investigate whether a medium-chain triglycerides (MCTs) replacement diet
mitigated the impaired male fertility by deletion of Atgl gene, homozygous Atgl
deficient mice were fed a MCT replacement diet, or a standard diet including long
chain triglycerides (LCTs) in a control group, for 6 weeks from 5 weeks of age (n
= 22). The systematic and local effects of the MCT replacement diet on
spermatogenesis and sperm maturation in the epididymis were analyzed at 10 weeks
of age. PARTICIPANTS/MATERIALS, SETTING, METHODS: Hematoxylin and eosin staining
in paraffin-embedded sections of testes and Oil Red O staining in frozen sections
of testes were performed. The epididymal sperm concentrations were analyzed.
Statistical analyses were performed using the Student's t-test or Mann-Whitney U
test with Shapiro-Wilk Normality test. MAIN RESULTS AND THE ROLE OF CHANCE:
Although heterozygous mice were fertile and showed a similar number of epididymal
total and motile sperm concentrations to wild-type mice, the deletion of Atgl
gene in homozygous mice led to accumulation of TG deposits in testes and impaired
spermatogenesis. The deletion of Atgl gene also impaired the sperm maturation
process required for sperm to acquire the ability to move forward in the
epididymis. The MCT replacement diet for 6 weeks increased the plasma level of
non-esterified fatty acid (NEFA) (1.5-fold, P = 0.005), but not the plasma total
cholesterol (T-Cho) and TG levels. In testes, the MCT replacement diet decreased
the number of Oil Red O stain positive vacuoles (-40%, P < 0.001) and increased
testis tissue weight (1.1-fold, P = 0.012), total sperm concentration (1.5-fold,
P = 0.011) and motile sperm concentration (2.1-fold, P < 0.001) compared to the
control group. However, there was no significant change in the sperm survival
rate between the two groups. LARGE SCALE DATA: None. LIMITATIONS REASONS FOR
CAUTION: One previous study reported that Atgl-deficient male mice were fertile.
In most studies heterozygous Atgl(+/-) mice were used to generate homozygous Atgl
deficient Atgl(-/-) mice. Although the same gene targeting mice were used in this
study and the formation of vaginal plugs were observed after mating with Atgl(-/
) male mice, there were no pregnant wild-type mice observed after mating with
Atgl(-/-) male mice. WIDER IMPLICATIONS OF THE FINDINGS: Local TG metabolism in
the male reproductive system could affect spermatogenesis and sperm motility in
men. The MCT replacement diet could be an effective therapy for idiopathic non
obstructive oligozoospermia or asthenozoospermia in men with low levels of serum
NEFA. STUDY FUNDING AND COMPETING INTEREST(S): This study was supported in part
by the Japan Society for the Promotion of Science JSPS KAKENHI Grant (Nos.
JP24249080, JP25462557, JP16K11086). The authors declare no conflict of interest.
PMID- 28510705
TI - Crystal structure of octocoral lectin SLL-2 complexed with Forssman antigen
tetrasaccharide.
AB - A symbiosis-related lectin, SLL-2, from the octocoral Sinularia lochmodes,
distributes densely on the cell surface of microalgae, Symbiodinium sp., an
endosymbiotic dinoflagellate of the coral, and is also shown to be a chemical cue
that transforms dinoflagellates into a non-motile (coccoid) symbiotic state. SLL
2 binds to the sugar chain of the molecule similar to Forssman antigen
pentasaccharide (GalNAcalpha1-3GalNAcbeta1-3 Galalpha1-4 Galbeta1-4Glc) on the
surface of microalgae with high affinity. Here we report the crystal structure of
the complex between SLL-2 and Forssman antigen tetrasaccharide (GalNAcalpha1
3GalNAcbeta1-3 Galalpha1-4 Galbeta) at 3.4 A resolution. In an asymmetric unit of
the crystal, there are two hexameric molecules with totally twelve sugar
recognition sites. At the nine in twelve sites, the first and second saccharides
of the Forssman antigen tetrasaccharide bind directly to galactopyranoside
binding site of SLL-2, whereas the third and fourth saccharides have no
interaction with the SLL-2 hexameric molecule that binds the first saccharide.
The sugar chain bends at alpha-1,4-glycosidic linkage between the third and
fourth saccharides toward the position that we defined as a pyranoside binding
site in the crystal structure of the complex between SLL-2 and GalNAc. The
structure allowed us to suggest a possible binding mode of the Forssman antigen
pentasaccharide to SLL-2. These observations support our hypothesis that the
binding of SLL-2 to the cell surface sugars of zooxanthella in a unique manner
might trigger some physiological changes of the cell to adapt symbiosis with the
host coral.
PMID- 28510707
TI - Policing Intimate Partner Violence: Attitudes toward Risk Assessment and
Collaboration with Social Workers.
AB - Risk-informed collaborative police-social service interventions are an emerging
strategy intended to enhance offender accountability and victim-survivors' safety
in intimate partner violence (IPV) cases. These interventions use risk assessment
to determine appropriate interventions and enhance the police response for
dangerous offenders by engaging in collaboration with social work advocates.
Because little is known about the responsiveness of police officers to risk
informed collaborative interventions, this study examines police officer (N =
544) attitudes toward IPV risk assessment and collaboration with social workers.
The majority of police officers did not believe a social worker would be helpful
at the scene of an IPV incident. However, those who agreed that a social worker
would be helpful were more likely to be knowledgeable about the dynamics of IPV.
Officers who believed risk assessment was important were more likely to believe
that the police response to IPV is necessary. Finally, officers' perceived
knowledge about risk for homicide was not consistently associated with actual
knowledge about IPV. These findings suggest a need for knowledgeable social
workers to collaborate with police, particularly in high-risk cases, and to offer
training for officers on risk factors for homicide, coercive control, and
misperceptions about IPV.
PMID- 28510709
TI - Clopidogrel instead of prasugrel or ticagrelor after 1 month in stabilized ACS
patients: back to square one for DAPT?
PMID- 28510706
TI - Two Imported Cases of Congenital Rubella Syndrome and Infection-Control
Challenges in New York State, 2013-2015.
AB - Rubella was declared eliminated in the United States in 2004. During 2013-2015, 2
infants with congenital rubella syndrome (CRS) were born in New York State. Both
mothers were foreign born and traveled to Yemen during their pregnancy. Delayed
consideration of CRS led to preventable exposures and a substantial public health
response.
PMID- 28510708
TI - Aberrant White Matter Microstructure in Children and Adolescents With the Subtype
of Prader-Willi Syndrome at High Risk for Psychosis.
AB - Prader-Willi Syndrome (PWS) is a complex neurogenetic disorder caused by loss of
the paternal 15q11.2-q13 locus, due to deletion (DEL), maternal uniparental
disomy (mUPD), or imprinting center defects. Individuals with mUPD have up to 60%
risk of developing psychosis in early adulthood. Given the increasing evidence
for white matter abnormalities in psychotic disorders, we investigated white
matter microstructure in children and adolescents with PWS, with a particular
emphasis on the DEL and mUPD subtypes. Magnetic resonance diffusion weighted
images were acquired in 35 directions at 3T and analyzed using fractional
anisotropy (FA), mean, axial, and radial diffusivity (MD, AD, RD) values obtained
by tract-based spatial statistics (TBSS) in 28 children and adolescents with PWS
and 61 controls. In addition, we employed a recently developed white matter
pothole approach, which does not require local FA differences to be spatially co
localized across subjects. After accounting for age and gender, individuals with
PWS had significantly lower global FA and higher MD, compared with controls.
Individuals with mUPD had lower FA in multiple regions including the corpus
callosum, cingulate, and superior longitudinal fasciculus and larger potholes,
compared with DEL and controls. The observed differences in individuals with mUPD
are similar to the white matter abnormalities in individuals with psychotic
disorders. Conversely, the subtle white matter abnormalities in individuals with
DEL are consistent with their substantially lower risk of psychosis. Future
studies to investigate the specific neurobiological mechanism underlying the
differential psychosis risk between the DEL and mUPD subtypes of PWS are highly
warranted.
PMID- 28510710
TI - Relationship Between Objectively Measured Physical Activity, Cardiovascular
Disease Biomarkers, and Hearing Sensitivity Using Data From the National Health
and Nutrition Examination Survey 2003-2006.
AB - Purpose: Limited research has examined the interrelationships among
cardiometabolic parameters, physical activity, and hearing function, which was
this study's purpose. Method: Data from the National Health and Nutrition
Examination Survey (NHANES) 2003-2006 were used in the path analyses. Physical
activity and hearing function were both objectively measured. Various
cardiometabolic parameters were assessed from a blood sample. Adults 30-85 years
(N = 1,070) constituted the analytic sample. Results: Physical activity was
negatively associated with triglycerides (beta = -0.11, p < .05) and insulin
(beta = -0.27, p < .05); triglycerides (beta = 0.01, p < .05), and insulin (beta
= 0.05, p < .05) were positively associated with high-frequency pure-tone average
(HPTA). The direct path from physical activity to HPTA was nonsignificant (beta =
0.01, p = .99). Conclusion: Physical activity was associated with select
cardiovascular disease risk factors. Several cardiovascular disease risk factors
were associated with hearing function.
PMID- 28510711
TI - Obesity and Metabolic Unhealthiness Have Different Effects on Colorectal
Neoplasms.
AB - Context: Obesity and insulin resistance are risk factors for colorectal neoplasms
(CRN), but data regarding metabolic status, obesity, and CRN are lacking.
Objective: To investigate the relationship between metabolic status, obesity, and
CRN in Koreans who underwent colonoscopy. Design: Retrospective, cross-sectional.
Participants: Subjects were divided based on metabolic and obesity criteria, as
follows: metabolically healthy nonobese (MHNO), metabolically healthy obese
(MHO), metabolically unhealthy nonobese (MUNO), and metabolically unhealthy obese
(MUO). Main Outcome Measures: Multiple regression was used to identify CRN and
advanced CRN risk factors, with the MHNO group as reference. Results: A total of
10,235 subjects was included, as follows: 5096 MHNO, 1538 MHO, 1746 MUNO, and
1855 MUO. Of these, 3297 had CRN (32.2%), and 434 (4.2%) had advanced CRN. Number
of subjects with CRN in each group were: MHNO 25.8%, MHO 33.9%, MUNO 38.9%, and
MUO 42.0% (P for trend < 0.001). Risk of CRN was increased in the MHO [odds ratio
(OR) 1.239, 95% confidence interval (CI) 1.082 to 1.418, P = 0.002], the MUNO (OR
1.233, 95% CI 1.086 to 1.400, P = 0.001), and the MUO groups (OR 1.510, 95% CI
1.338 to 1.706, P < 0.001), whereas risk of advanced CRN was increased in the
MUNO (OR 1.587, 95% CI 1.222 to 2.062, P = 0.001) and the MUO groups (OR 1.456,
95% CI 1.116 to 1.900, P = 0.006). Conclusions: Obesity increased CRN risk with
metabolically unhealthy status adding risk. For advanced CRN, metabolically
unhealthy status increased the risk but obesity did not.
PMID- 28510712
TI - Gender issues in arrhythmias: from atrial fibrillation to CRT and arrhythmogenic
ventricular cardiomyopathy.
PMID- 28510713
TI - RE: "DISASTERS: INTRODUCTION AND STATE OF THE ART".
PMID- 28510714
TI - RE: "WHAT DO WE KNOW ABOUT THE ASSOCIATION BETWEEN FIREARM LEGISLATION AND
FIREARM-RELATED INJURIES?"
PMID- 28510715
TI - Quantitative specificity of STAT1 and several variants.
AB - The quantitative specificity of the STAT1 transcription factor was determined by
measuring the relative affinity to hundreds of variants of the consensus binding
site including variations in the length of the site. The known consensus sequence
is observed to have the highest affinity, with all variants decreasing binding
affinity considerably. There is very little loss of binding affinity when the CpG
within the consensus binding site is methylated. Additionally, the specificity of
mutant proteins, with variants of amino acids that interact with the DNA, was
determined and nearly all of them are observed to lose specificity across the
entire binding site. The change of Asn at position 460 to His, which corresponds
to the natural amino acid at the homologous position in STAT6, does not change
the specificity nor does it change the length preference to match that of STAT6.
These results provide the first quantitative analysis of changes in binding
affinity for the STAT1 protein, and several variants of it, to hundreds of
different binding sites including different spacer lengths, and the effect of CpG
methylation.
PMID- 28510717
TI - Fast Population Growth in Physogastry Reproduction of Luciaphorus perniciosus
(Acari: Pygmephoridae) at Different Temperatures.
AB - Luciaphorus perniciosus Rack is one of the most serious pests of several
cultivated mushroom species including Ganoderma lucidum (Fr.), Flammulina
velutipes Karst., Auricularia polytricha (Mont.) Saac., Lentinus polychrous Lev.,
and Lentinus squarrosulus (Mont.) Singer in Thailand. Adult female Lu.
perniciosus produce offspring inside their physogastric hysterosomas, with all
embryos developing through to the adult stage while remaining in the abdomen.
Once the abdomen ruptures, the female parent dies and the offspring consisting of
mostly fertilized female adults along with a few male adults continue to emerge
from the cadaver of the mother for a period of several days. This peculiar type
of reproduction after the death of the mother is a special case for life table
analysis and has not been discussed previously in demographic analyses. In this
study, the life table data of this mite fed on Le. squarrosulus were collected at
25, 30, and 35 degrees C and analyzed by using the age-stage, two-sex life
table. The standard errors of population parameters were estimated by using the
bootstrap technique (200,000 bootstraps). At 25, 30, and 35 degrees C, females
started reproduction at ages 9, 5, and 3 d, respectively; the net reproductive
rates (R0) were 192.27, 253.81, and 234.11 offspring. Due to their rapid
development and high fecundity, the r values were as high as 0.4189, 0.8653, and
1.0892 d-1 at 25, 30, and 35 degrees C, respectively. Computer projection
indicated that the mushroom mites Lu. perniciosus is capable of a threefold daily
increase at 35 degrees C.
PMID- 28510716
TI - Phosphorylation of the transcriptional repressor MYB15 by mitogen-activated
protein kinase 6 is required for freezing tolerance in Arabidopsis.
AB - The expression of CBF (C-repeat-binding factor) genes is required for freezing
tolerance in Arabidopsis thaliana. CBFs are positively regulated by INDUCER OF
CBF EXPRESSION1 (ICE1) and negatively regulated by MYB15. These transcription
factors directly interact with specific elements in the CBF promoters. Mitogen
activated protein kinase (MAPK/MPK) cascades function upstream to regulate CBFs.
However, the mechanism by which MPKs control CBF expression during cold stress
signaling remains unknown. This study showed that the activity of MYB15, a
transcriptional repressor of cold signaling, is regulated by MPK6-mediated
phosphorylation. MYB15 specifically interacts with MPK6, and MPK6 phosphorylates
MYB15 on Ser168. MPK6-induced phosphorylation reduced the affinity of MYB15
binding to the CBF3 promoter and mutation of its phosphorylation site
(MYB15S168A) enhanced the transcriptional repression of CBF3 by MYB15.
Furthermore, transgenic plants overexpressing MYB15S168A showed significantly
reduced CBF transcript levels in response to cold stress, compared with plants
overexpressing MYB15. The MYB15S168A-overexpressing plants were also more
sensitive to freezing than MYB15-overexpressing plants. These results suggest
that MPK6-mediated regulation of MYB15 plays an important role in cold stress
signaling in Arabidopsis.
PMID- 28510719
TI - Featured Article: Trajectories of Glycemic Control Over Adolescence and Emerging
Adulthood: An 11-Year Longitudinal Study of Youth With Type 1 Diabetes.
AB - Objective: To identify trajectories of glycemic control over adolescence and
emerging adulthood and to test whether demographic and psychosocial variables
distinguished these trajectories. Methods: We enrolled 132 youth with type 1
diabetes when they were average age 12 and followed them for 11 years. We used
group-based trajectory modeling to identify distinct patterns of glycemic
control, and examined whether age 12 demographic and psychosocial variables
distinguished the subsequent trajectories. Results: We identified 5 trajectories
of glycemic control: stable on target, stable above target, volatile late peak,
stable high, and inverted U. Parent social status and household structure
distinguished the more problematic trajectories from the stable on target group.
Friend conflict, psychological distress, unmitigated communion, and self-care
behavior at age 12 distinguished problematic glycemic control trajectories from
the stable on target group. Conclusions: These results can be used to identify
youth who are at risk for deteriorating glycemic control over adolescence.
PMID- 28510718
TI - Multimodality Imaging in Restrictive Cardiomyopathies: An EACVI expert consensus
document In collaboration with the "Working Group on myocardial and pericardial
diseases" of the European Society of Cardiology Endorsed by The Indian Academy of
Echocardiography.
AB - Restrictive cardiomyopathies (RCMs) are a diverse group of myocardial diseases
with a wide range of aetiologies, including familial, genetic and acquired
diseases and ranging from very rare to relatively frequent cardiac disorders. In
all these diseases, imaging techniques play a central role. Advanced imaging
techniques provide important novel data on the diagnostic and prognostic
assessment of RCMs. This EACVI consensus document provides comprehensive
information for the appropriateness of all non-invasive imaging techniques for
the diagnosis, prognostic evaluation, and management of patients with RCM.
PMID- 28510720
TI - Effects of a 3D segmental prosthetic system for tricuspid valve annulus
remodelling on the right coronary artery: a human cadaveric coronary angiography
study.
AB - OBJECTIVES: A prosthetic system to repair secondary tricuspid valve regurgitation
was developed. The conceptual engineering of the current device is based on 3D
segmental remodelling of the tricuspid valve annulus in lieu of reductive
annuloplasty. This study was designed to investigate the operational safety of
the current prosthetic system with regard to the anatomical integrity of the
right coronary artery (RCA) in fresh cadaveric human hearts. METHODS: During the
study period, from January to April 2016, the current prosthetic system was
implanted on the tricuspid valve annulus in fresh cadaveric human hearts that met
the study's inclusion criteria. The prepared specimens were investigated via
selective coronary angiography of the RCA in the catheterization laboratory. The
RCA angiographic anatomies were categorized as normal, distorted, kinked or
occluded. RESULTS: Sixteen specimens underwent implantation of the current
prosthetic system. The mean age of the cadaveric human hearts was 43.24 +/- 15.79
years, with vehicle accident being the primary cause of death (59%). A dominant
RCA was noticed in 62.5% of the specimens. None of the specimens displayed any
injury, distortion, kinking or occlusion in the RCA due to the implantation of
the prostheses. CONCLUSIONS: In light of the results of the present study,
undertaken on fresh cadaveric human heart specimens, the current segmental
prosthetic system for 3D remodelling of the tricuspid valve annulus seems to be
safe vis-a-vis the anatomical integrity of the RCA. Further in vivo studies are
needed to investigate the functional features of the current prosthetic system
with a view to addressing the complex pathophysiology of secondary tricuspid
valve regurgitation.
PMID- 28510722
TI - Clinical Markers and Outcomes of Neonates With Herpes Simplex Virus
Deoxyribonucleic Acid Persistence in Cerebrospinal Fluid in Disseminated and
Central Nervous System Infection.
AB - We compared the clinical course of neonates with persistence of herpes simplex
virus (HSV) deoxyribonucleic acid (DNA) in the cerebrospinal fluid (CSF) after 21
days of treatment with high-dose acyclovir to that of neonates with clearance of
the CSF after 21 days of therapy. Neonates with persistence of HSV DNA had a more
severe clinical course with worse neurodevelopmental outcomes.
PMID- 28510721
TI - Cold Tolerance of Pityophthorus juglandis (Coleoptera: Scolytidae) From Northern
California.
AB - Winter survivorship of insects is determined by a combination of physiological,
behavioral, and microhabitat characteristics. We characterized the cold tolerance
of the walnut twig beetle, Pityophthorus juglandis Blackman, a domestic alien
invasive bark beetle that vectors a phytopathogenic fungus. The beetle and fungus
cause thousand cankers disease in species of Juglans and Pterocarya. The disease
is spreading in the United States of America (USA) and Italy. Contact
thermocouple thermometry was used to measure the supercooling points of adults
and larvae and lower lethal temperatures of adults from a population from
northern California. Supercooling points ranged from -12.2 degrees C to - 25.0
degrees C for adults and -13.6 degrees C to - 23.5 degrees C for larvae; lower
lethal temperatures of adults ranged from -14 degrees C to - 23 degrees C. We
found seasonal changes in adult supercooling points in fall, winter, and spring.
The supercooling point for males was 0.5 degrees C colder than for females over
all months and 1 degrees C colder in the winter than in other seasons. The cold
tolerance strategy shifted in P. juglandis adults from freeze intolerance
(December 2013 and January 2014) to partial freeze tolerance (February 2014). An
intermediate level of cold tolerance with a plastic response to cold partially
explains survival of P. juglandis outside of its native range in the southwestern
USA. In addition, we characterized the relationship between minimum air
temperatures and minimum phloem temperatures in two Juglans spp. in northern
California and Colorado and characterized portions of the native geographic range
of eastern black walnut, J. nigra L., that may be too cold currently for this
insect to persist.
PMID- 28510723
TI - Decreased Azithromycin Susceptibility of Neisseria gonorrhoeae Isolates in
Patients Recently Treated with Azithromycin.
AB - Background: Increasing azithromycin usage and resistance in Neisseria gonorrhoeae
threatens current dual treatment. Because antimicrobial exposure influences
resistance, we analyzed the association between azithromycin exposure and
decreased susceptibility of N. gonorrhoeae. Methods: We included N. gonorrhoeae
isolates of patients who visited the Amsterdam STI Clinic between 1999 and 2013
(t0), with another clinic visit in the previous 60 days (t-1). Exposure was
defined as the prescription of azithromycin at t-1. Using multivariable linear
regression, we assessed the association between exposure and azithromycin minimum
inhibitory concentration (MIC). Whole genome sequencing (WGS) was performed to
produce a phylogeny and identify multilocus sequence types (MLST), N. gonorrhoeae
multiantigen sequence types (NG-MAST), and molecular markers of azithromycin
resistance. Results: We included 323 isolates; 212 were unexposed to
azithromycin, 14 were exposed <=30 days, and 97 were exposed between 31 and 60
days before isolation. Mean azithromycin MIC was 0.28 mg/L (range, <0.016-24
mg/L). Linear regression adjusted for age, ethnicity, infection site, and
calendar year showed a significant association between azithromycin exposure <=30
days and MIC (beta, 1.00; 95% confidence interval, 0.44-1.56; P = .002). WGS was
performed on 31 isolates: 14 unexposed, 14 exposed to azithromycin <=30 days
before isolation, and 3 t-1 isolates. Exposure to azithromycin was significantly
associated with A39T or G45D mtrR mutations (P = .046) but not with MLST or NG
MAST types. Conclusions: The results suggest that frequent azithromycin use in
populations at high risk of contracting N. gonorrhoeae induces an increase in MIC
and may result in resistance.
PMID- 28510724
TI - Relationship between the magnetic resonance imaging appearance of adenomyosis and
endometriosis phenotypes.
AB - STUDY QUESTION: What is the relationship between endometriosis phenotypes
superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA), deep
infiltrating endometriosis (DIE) and the adenomyosis appearance by magnetic
resonance imaging (MRI)? SUMMARY ANSWER: Focal adenomyosis located in the outer
myometrium (FAOM) was observed more frequently in women with endometriosis, and
was significantly associated with the DIE phenotype. WHAT IS KNOWN ALREADY: An
association between endometriosis and adenomyosis has been reported previously,
although data regarding the association between MRI appearance of adenomyosis and
the endometriosis phenotype are currently still lacking. STUDY DESIGN, SIZE,
DURATION: This was an observational, cross-sectional study using data
prospectively collected from non-pregnant patients who were between 18 and 42
years of age, and who underwent surgery for symptomatic benign gynecological
conditions between January 2011 and December 2014. For each patient, a
standardized questionnaire was completed during a face-to-face interview
conducted by the surgeon during the month preceding the surgery. Only women with
preoperative standardized uterine MRIs were retained for this study.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Surgery was performed on 292 patients
with signed consent and available preoperative MRIs. After a thorough surgical
examination of the abdomino-pelvic cavity, 237 women with histologically proven
endometriosis were allocated to the endometriosis group and 55 symptomatic women
without evidence of endometriosis to the endometriosis free group. The existence
of diffuse or FAOM was studied in both groups and according to surgical
endometriosis phenotypes (SUP, OMA and DIE). MAIN RESULTS AND THE ROLE OF CHANCE:
Adenomyosis was observed in 59.9% (n = 175) of the total sample population (n =
292). Based on MRI, the distribution of adenomyosis was as follows: isolated
diffuse adenomyosis (53 patients; 18.2%), isolated FAOM (74 patients; 25.3%),
associated diffuse and FAOM (48 patients; 16.4%). Diffuse adenomyosis (isolated
and associated to FAOM) was observed in one-third of the patients regardless of
whether they were endometriotic patients or endometriosis free women taken as
controls (34.2% (81 cases) versus 36.4% (20 cases)); P = 0.764. Among
endometriotic women, diffuse adenomyosis (isolated and associated to FAOM) failed
to reach significant correlation with the endometriosis phenotypes (SUP, 20.0% (8
cases); OMA, 45.2% (14 cases) and DIE, 35.5% (59 cases); P = 0.068). In striking
contrast, there was a significant increase in the frequency of FAOM in
endometriosis-affected women than in controls (119 cases (50.2%) versus 5.4% (3
cases); P < 0.001). FAOM correlated with the endometriosis phenotypes,
significantly with DIE (SUP, 7.5% (3 cases); OMA, 19.3% (6 cases) and DIE, 66.3%
(110 cases); P < 0.001). LIMITATIONS, REASONS FOR CAUTION: There was a possible
selection bias due to the specificity of the study design, as it only included
surgical patients in a referral center that specializes in endometriosis surgery.
Therefore, women referred to our center may have suffered from particularly
severe forms of endometriosis. This could explain the high number of women with
DIE (166/237-70%) in our study group. This referral bias for women with severe
lesions may have amplified the difference in association of FAOM with the
endometriosis-affected patients compared to women without endometriosis.
Furthermore, according to inclusion criteria, women in the endometriosis free
group were symptomatic women. This may introduce some bias as symptomatic women
may be more prone to have associated adenomyosis that in turn could have been
overrepresented in the endometriosis free group. Whether this selection could
have introduced a bias in the relationship between endometriosis and adenomyosis
remains unknown. WIDER IMPLICATIONS OF THE FINDINGS: This study opens the door to
future epidemiological, clinical and mechanistic studies aimed at better
characterizing diffuse and focal adenomyosis. Further studies are necessary to
adequately determine if diffuse and focal adenomyosis are two separate entities
that differ in terms of pathogenesis. STUDY FUNDING/COMPETING INTEREST(S): No
funding supported this study. The authors have no conflict of interest to
declare.
PMID- 28510726
TI - Conflict Strategies in the Parent-Adult Child Tie: Generation Differences and
Implications for Well-Being.
AB - Objectives: Irritations often arise in intergenerational ties. Middle-aged
individuals report that their relationships with adult children are more
important and more negative than ties with aging parents. However, it is unclear
whether midlife individuals use different interpersonal conflict strategies with
adult children compared to aging parents, and whether the strategies used have
implications for psychological well-being. Method: This study examined middle
aged individuals' reports of conflict strategies with their adult children and
their aging parents and their own depressive symptoms. Participants were from the
Family Exchanges Study; middle-aged adults (N = 365, ages 45 to 66 years)
reported on the conflict strategies used with each of their adult children and
their aging parents. Results: Models revealed that middle-aged individuals use
more active strategies (e.g., discussing problems) with their adult children than
their aging parents. In contrast, individuals used more passive strategies (e.g.,
avoidance) with aging parents than adult children. Further, passive strategies
used with adult children are associated with greater depressive symptoms.
Discussion: Findings are consistent with the intraindividual stake hypothesis and
imply that conflict strategies used with adult children may be more consequential
for psychological well-being than those used with aging parents.
PMID- 28510725
TI - IFITM3, TLR3, and CD55 Gene SNPs and Cumulative Genetic Risks for Severe Outcomes
in Chinese Patients With H7N9/H1N1pdm09 Influenza.
AB - Background: We examined associations between single-nucleotide polymorphisms
(SNPs) of IFITM3, TLR3, and CD55 genes and influenza clinical outcomes in
Chinese. Methods: A multicenter study was conducted on 275 adult cases of avian
(H7N9) and pandemic (H1N1pdm09) influenza. Host DNA was extracted from diagnostic
respiratory samples; IFITM3 rs12252, TLR3 rs5743313, CD55 rs2564978, and TLR4
rs4986790/4986791 were targeted for genotyping (Sanger sequencing). The primary
outcome analyzed was death. Results: IFITM3 and TLR3 SNPs were in Hardy-Weinberg
equilibrium; their allele frequencies (IFITM3/C-allele 0.56, TLR3/C-allele 0.88)
were comparable to 1000 Genomes Han Chinese data. We found over-representation of
homozygous IFITM3 CC (54.5% vs 33.2%; P = .02) and TLR3 CC (93.3% vs 76.9%; P =
.04) genotypes among fatal cases. Recessive genetic models showed their
significant independent associations with higher death risks (adjusted hazard
ratio [aHR] 2.78, 95% confidence interval [CI] 1.29-6.02, and aHR 4.85, 95% CI
1.11-21.06, respectively). Cumulative effects were found (aHR 3.53, 95% CI 1.64
7.59 per risk genotype; aHR 9.99, 95% CI 1.27-78.59 with both). Results were
consistent for each influenza subtype and other severity indicators. The CD55 TT
genotype was linked to severity. TLR4 was nonpolymorphic. Conclusions: Host
genetic factors may influence clinical outcomes of avian and pandemic influenza
infections. Such findings have important implications on disease burden and
patient care in at-risk populations.
PMID- 28510727
TI - Alternative splicing in the C-terminal tail of Cav2.1 is essential for preventing
a neurological disease in mice.
AB - Alternative splicing (AS) that occurs at the final coding exon (exon 47) of the
Cav2.1 voltage-gated calcium channel (VGCC) gene produces two major isoforms in
the brain, MPI and MPc. These isoforms differ in their splice acceptor sites;
human MPI is translated into a polyglutamine tract associated with
spinocerebellar ataxia type 6 (SCA6), whereas MPc splices to an immediate stop
codon, resulting in a shorter cytoplasmic tail. To gain insight into the
functional role of the AS in vivo and whether modulating the splice patterns at
this locus can be a potential therapeutic strategy for SCA6, here we created
knockin mice that exclusively express MPc by inserting the splice-site mutation.
The resultant Cacna1aCtmKO/CtmKO mice developed non-progressive neurological
phenotypes, featuring early-onset ataxia and absence seizure without significant
alterations in the basic properties of the channel. Interactions of Cav2.1 with
Cavbeta4 and Rimbp2 were significantly reduced while those with GABAB2 were
enhanced in the cerebellum of Cacna1aCtmKO/CtmKO mice. Treatment with the GABAB
antagonist CGP35348 partially rescued the motor impairments seen in
Cacna1aCtmKO/CtmKO mice. These results suggest that the carboxyl-terminal domain
of Cav2.1 is not essential for maintaining the basic properties of the channel in
the cerebellar Purkinje neurons but is involved in multiple interactions of
Cav2.1 with other proteins, and plays an essential role in preventing a complex
neurological disease.
PMID- 28510729
TI - Political Social Work.
PMID- 28510728
TI - Spatial and Temporal Dynamics of Aphids (Hemiptera: Aphididae) in the Columbia
Basin and Northeastern Oregon.
AB - Aphid species, such as the potato aphid, Macrosiphum euphorbiae Thomas, and the
green peach aphid, Myzus persicae Sulzer, are routinely considered the most
important pests of potatoes. Potato aphid, green peach aphid, and more recently,
other aphids such as the bird cherry-oat aphid Rhopalosiphum padi L. have been
identified as vectors of multiple plant pathogenic viruses in potatoes. Since
2006, an area-wide trapping network consisting of ~60 sites was developed through
collaboration between researchers, extension faculty, and stakeholders, to
monitor aphid populations in the Columbia Basin of Oregon (Umatilla and Morrow
counties) and in northeastern Oregon (Union and Baker counties). Over a 9-yr
period (2006 to 2014), aphid specimens were collected weekly using yellow bucket
traps and specimens were then identified and counted to determine population
levels during the growing season (May-September). Thus, aphid population data
were compiled and subjected to spatial and temporal distribution analysis.
Weather data, obtained from an established network of weather stations located in
the monitoring areas, were used in a nonparametric multiplicative regression
analysis to determine which abiotic variables may impact aphid populations.
Weather conditions were characterized using confidence intervals (CIs)
established based on weather data from 1999 to 2005 for each environmental
variable. Aphid populations were found to have a heterogeneous distribution in
most years; a few sites had high aphid populations while low numbers were
observed at most sites; aphids were also found to correlate with several abiotic
variables, namely, elevation, previous season temperature, and previous season
dew point.
PMID- 28510730
TI - Trimethoprim/sulfamethoxazole versus vancomycin in the treatment of
healthcare/ventilator-associated MRSA pneumonia: a case-control study.
PMID- 28510731
TI - Letter: Retention of ATRX and DAXX Expression in Meningiomas.
PMID- 28510732
TI - Efficacy of Bistrifluron Termite Bait on Coptotermes lacteus (Isoptera:
Rhinotermitidae) in Southern Australia.
AB - Bistrifluron, a benzoylphenyl urea compound, was evaluated for efficacy against
Coptotermes lacteus (Froggatt), a mound-building species in southern Australia.
Bistrifluron bait (tradename Xterm) was delivered as containerized pellets
inserted into plastic in-ground feeding stations implanted in the sides of
mounds. Termites actively tunneled in the gaps between pellets and removed bait
from the canisters. Two separate trials were conducted, one commencing on 22
September 2011 and the second commencing on 30 November 2011. In trial 1, all 13
treated colonies (seven single and six double treatments) were eliminated within
19 wk, while all five untreated colonies remained healthy. In trial 2, all four
treated colonies were eliminated within 14 wk. In trial 1, bait consumed or
removed in treated mounds averaged 105 g for single treatments and 147 g for dual
treatments, and overall ranged from 7 to 309 g (70-3,090 mg bistrifluron). In
trial 2, the four treated colonies removed an average of 85 g of bait. At the
time mounds were dismantled, all showed signs of inattention: external cracking,
delamination, and general external weathering. Mound repair and temperature
profile data indicate that colony decline commenced much earlier than 19 wk and
14 wk, respectively, for trials 1 and 2, from as early as 4 wk onward. The
ability of colonies to repair mound damage was impaired as early as 4 wk in some
colonies, and mean internal mound temperatures in treated mounds began declining
from 8 wk onward and clearly diverged from mean temperatures of untreated mounds
thereafter.
PMID- 28510733
TI - RADON DOSIMETRY FOR WORKERS: ICRP'S APPROACH.
AB - The International Commission on Radiological Protection (ICRP) has recently
published two reports on radon exposure; Publication 115 on lung cancer risks
from radon and radon progeny and Publication 126 on radiological protection
against radon exposure. A specific graded approach for the control of radon in
workplaces is recommended where a dose assessment is required in certain
situations. In its forthcoming publication on Occupational Intakes of
Radionuclides (OIR) document, Part 3, effective dose coefficients for radon and
thoron will be provided. These will be calculated using ICRP reference biokinetic
and dosimetric models. Sufficient information and dosimetric data will be given
so that site-specific dose coefficients can be calculated based on measured
aerosol parameter values. However, ICRP will recommend a single dose coefficient
of 12 mSv per working level month (WLM) for inhaled radon progeny to be used in
most circumstances. This chosen reference value was based on both dosimetry and
epidemiological data. In this paper, the application and use of dose coefficients
for workplaces are discussed including the reasons for the choice of the
reference value. Preliminary results of dose calculations for indoor workplaces
and mines are presented. The paper also briefly describes the general approach
for the management of radon exposure in workplaces based both on ICRP
recommendations and the European directive (2013/59/EURATOM).
PMID- 28510735
TI - Spinal Cord Compression Related to Spinal Cord Stimulator.
PMID- 28510734
TI - Predictors of and outcomes following orthopaedic joint surgery in patients with
early rheumatoid arthritis followed for 20 years.
AB - Objectives: To analyse predictors and outcomes of major orthopaedic surgery in a
cohort of RA patients followed for 20 years. Methods: Patients were recruited to
the Norfolk Arthritis Register from 1990 to 1994. Demographic and clinical
variables (including the HAQ and swollen and tender joint counts) were assessed
at baseline; the 2010 ACR/EULAR RA classification criteria were applied. Patients
reported incident comorbidities and major orthopaedic joint surgery (replacement,
synovectomy, fusion, excision) when reassessed at years 1, 2, 3, 5, 7, 10, 15 and
20. Baseline and time-varying predictors of orthopaedic surgery were assessed
using a conditional risk set model, a type of multiple-failure survival analysis.
Change in disability after surgery was assessed using weighted mixed-effects
linear regression. Results: Of 589 RA patients [median age 56 years (IQR 45-68);
66.7% women] recruited to the Norfolk Arthritis Register with at least one follow
up, 102 reported a total of 180 major surgeries, with hip replacement being the
most common (n = 68/180). Patients reporting major surgery had worse functional
disability at all time points, but similar swollen/tender joint counts to those
without major surgery. Each unit increase in HAQ score was associated with a
doubling of the patient's risk of having surgery by the next assessment [hazard
ratio 2.11 per unit increase in HAQ (95% CI 1.64, 2.71)]. Patients had worse HAQ
scores after surgery than patients not undergoing surgery [beta = 0.17 (95% CI
0.03, 0.32)]. Conclusion: HAQ was the strongest predictor of future major
surgery. This supports the argument that HAQ should be included in routine
clinical assessment.
PMID- 28510736
TI - Go/no-go decision in anaesthesia: wide variation in risk tolerance amongst
anaesthetists.
AB - Background: The variability in risk tolerance in medicine is not well understood.
Parallels are often drawn between aviation and anaesthesia. The aviation industry
is perceived as culturally risk averse, and part of preflight checks involves a
decision on whether the flight can operate. This is sometimes termed a go/no-go
decision. This questionnaire study was undertaken to explore the equivalent go/no
go decision in anaesthesia. We presented anaesthetists with a range of situations
in which additional risk might be expected and asked them to decide whether they
would proceed with the case. Methods: An electronic questionnaire was distributed
to anaesthetic colleagues of all grades in one National Health Service Trust.
Eleven scenarios, all drawn from critical incident data, were presented.
Participants were invited to consider whether they would proceed, how they would
modify their anaesthetic technique, and to predict whether a colleague with
similar experience would make the same decision. Textual responses were analysed
qualitatively. Results: The scenario response rate was 28%. Consultants were
significantly more likely to proceed than trainees. In no scenario was there
absolute agreement over whether to proceed, even in scenarios where national
guidelines would suggest a case should be cancelled. Thematic analysis suggested
a wide variability in what anaesthetists consider acceptable or professional
behaviour. Conclusions: It is clear that safety decisions cannot be made in
isolation and that clinicians must consider operational requirements, such as
throughput, when making a go/no-go decision. The level of variability in decision
making was surprising, particularly for scenarios that appeared to go against
guidelines.
PMID- 28510737
TI - Total haemoglobin mass, but not haemoglobin concentration, is associated with
preoperative cardiopulmonary exercise testing-derived oxygen-consumption
variables.
AB - Background: Cardiopulmonary exercise testing (CPET) measures peak exertional
oxygen consumption ( VO2peak ) and that at the anaerobic threshold ( VO2 at AT,
i.e. the point at which anaerobic metabolism contributes substantially to overall
metabolism). Lower values are associated with excess postoperative morbidity and
mortality. A reduced haemoglobin concentration ([Hb]) results from a reduction in
total haemoglobin mass (tHb-mass) or an increase in plasma volume. Thus, tHb-mass
might be a more useful measure of oxygen-carrying capacity and might correlate
better with CPET-derived fitness measures in preoperative patients than does
circulating [Hb]. Methods: Before major elective surgery, CPET was performed, and
both tHb-mass (optimized carbon monoxide rebreathing method) and circulating [Hb]
were determined. Results: In 42 patients (83% male), [Hb] was unrelated to VO2 at
AT and VO2peak ( r =0.02, P =0.89 and r =0.04, P =0.80, respectively) and
explained none of the variance in either measure. In contrast, tHb-mass was
related to both ( r =0.661, P <0.0001 and r =0.483, P =0.001 for VO2 at AT and
VO2peak , respectively). The tHb-mass explained 44% of variance in VO2 at AT ( P
<0.0001) and 23% in VO2peak ( P =0.001). Conclusions: In contrast to [Hb], tHb
mass is an important determinant of physical fitness before major elective
surgery. Further studies should determine whether low tHb-mass is predictive of
poor outcome and whether targeted increases in tHb-mass might thus improve
outcome.
PMID- 28510738
TI - Pharmacokinetic/pharmacodynamic model for unfractionated heparin dosing during
cardiopulmonary bypass.
AB - Background: High-dose heparin is used during cardiopulmonary bypass (CPB) to
prevent thrombosis in the circuits used for extracorporeal circulation. The aim
of this study was, initially, to develop a population
pharmacokinetic/pharmacodynamic (PK/PD) model to assess the variability of PK/PD
parameters and their correlation with the results of the routine haemostatic test
activated clotting time (ACT) and thereafter to develop a Bayesian estimator
enabling an individualized dosing strategy. Methods: Fifty consecutive patients
undergoing cardiac surgery with CPB were included in the study. Heparin was
administered as an initial bolus of 300 IU kg -1 followed by additional boluses
of 5000 IU to maintain ACT <400 s. In total, 361 blood samples were collected.
The PK and PD data were analysed using a non-linear mixed effect model. Results:
A two-compartment model with a linear elimination link to an E max model best
described heparin anti-factor Xa activities and ACT. Covariate analysis showed
that body weight was positively correlated with clearance and central compartment
volume. Inclusion of body weight with these parameters decreased their
variability by 11 and 15%, respectively. The Bayesian estimator performed well in
predicting individual parameters in an independent group of patients.
Conclusions: A population PK/PD analysis of heparin during CPB, using a routine
haemostatic test, shows that Bayesian estimation might help to predict ACT on the
basis of only one or two blood samples.
PMID- 28510739
TI - Comparison of preoperative and intraoperative assessment of aortic stenosis
severity by echocardiography.
AB - Background: General anaesthesia and surgically induced changes in cardiac loading
conditions may alter flow across the aortic valve. This study examined how
echocardiographic assessment of the severity of aortic stenosis (AS) changes
during surgery. Methods: Patients who underwent aortic valve replacement for any
severity of AS between July 2007 and June 2015 were identified. Peak velocities,
mean gradients, and dimensionless indices (DI) measured with preoperative
transthoracic echocardiography (TTE) were compared with those measured with
intraoperative transoesophageal echocardiography (TOE). Additionally, agreement
of preoperative and intraoperative grading of AS based on these measurements was
assessed. Results: Data from 319 patients were analysed. On average,
intraoperative TOE peak velocity and mean gradient were lower by 0.59 m s -1 and
12.5 mm Hg, respectively ( P <0.0001), compared with preoperative TTE
measurements, whereas the difference in mean DI was minimal at 0.008.
Preoperative and intraoperative grades of AS severity (mild, moderate, and
severe) by peak velocity, mean gradient, and DI agreed in 53.3, 53.7, and 83.3%
of patients, respectively. The TOE grade of AS severity by peak velocity and mean
gradient was at least one lower than the TTE grade in 45.1 and 42.7% of patients,
respectively. Significantly fewer patients had their severity of AS reclassified
based on DI ( P <0.0001). Conclusions: Intraoperative TOE peak velocities and
mean gradients are often significantly lower than preoperative TTE measurements,
leading to underestimation of AS severity in nearly half of our study patients.
The DI is a more reliable measurement of AS severity in the intraoperative
setting.
PMID- 28510740
TI - Propofol-based anaesthesia versus sevoflurane-based anaesthesia for living donor
kidney transplantation: results of the VAPOR-1 randomized controlled trial.
AB - Background: Kidney transplantation is associated with harmful processes affecting
the viability of the graft. One of these processes is associated with the
phenomenon of ischaemia-reperfusion injury. Anaesthetic conditioning is a widely
described strategy to attenuate ischaemia-reperfusion injury. We therefore
conducted the Volatile Anaesthetic Protection of Renal Transplants-1 trial, a
pilot project evaluating the influence of two anaesthetic regimens, propofol- vs
sevoflurane-based anaesthesia, on biochemical and clinical outcomes in living
donor kidney transplantation. Methods: Sixty couples were randomly assigned to
the following three groups: PROP (donor and recipient propofol), SEVO (donor and
recipient sevoflurane), and PROSE (donor propofol and recipient sevoflurane). The
primary outcome was renal injury reflected by urinary biomarkers. The follow-up
period was 2 yr. Results: Three couples were excluded, leaving 57 couples for
analysis. Concentrations of kidney injury molecule-1 (KIM-1), N -acetyl-beta- d
glucosaminidase (NAG), and heart-type fatty acid binding protein (H-FABP) in the
first urine upon reperfusion showed no differences. On day 2, KIM-1
concentrations were higher in SEVO [952.8 (interquartile range 311.8-1893.0) pg
mmol -1 ] compared with PROP [301.2 (202.0-504.7) pg mmol -1 ]. This was the same
for NAG: SEVO, 1.835 (1.162-2.457) IU mmol -1 vs PROP, 1.078 (0.819-1.713) IU
mmol -1 . Concentrations of H-FABP showed no differences. Measured glomerular
filtration rate at 3, 6, and 12 months showed no difference. After 2 yr, there
was a difference in the acute rejection rate ( P =0.039). Post hoc testing
revealed a difference between PROP (35%) and PROSE (5%; P =0.020). The difference
between PROP and SEVO (11%) was not significant ( P =0.110). Conclusions: The
SEVO group showed higher urinary KIM-1 and NAG concentrations in living donor
kidney transplantation on the second day after transplantation. This was not
reflected in inferior graft outcome. Clinical trial registration: NCT01248871.
PMID- 28510741
TI - Early or late fresh frozen plasma administration in newborns and small infants
undergoing cardiac surgery: the APPEAR randomized trial.
AB - Background: In newborns and small infants undergoing cardiac surgery with
cardiopulmonary bypass (CPB) and blood priming, it is unclear whether there is
reduced blood loss if fresh frozen plasma (FFP) is added to the CPB priming
volume. This single-centre, randomized trial tested the hypothesis that the
administration of FFP after CPB (late FFP group) is superior to FFP priming
(early FFP group) in terms of postoperative bleeding and overall red blood cell
(RBC) transfusion. Methods: Seventy-three infants weighing <10 kg were randomly
allocated to receive FFP to supplement RBCs in the CPB priming solution ( n =36)
or immediately after CPB ( n =37). The primary endpoint was a difference in
postoperative blood loss; secondary endpoints included the amount of RBCs and FFP
transfused through the first 48 postoperative hours. Results: All patients were
included in the analysis. Patients in the late FFP arm had greater postoperative
mean blood loss than patients in the early FFP arm [33.1 ( sd 20.6) vs 24.1
(12.9) ml kg -1 ; P =0.028], but no differences in transfusions were found. The
subgroup of cyanotic heart disease patients had comparable results, but with
greater use of RBCs in the late FFP group. Conclusions: In infants undergoing
cardiac surgery, FFP in the priming solution appears slightly superior to late
administration in terms of postoperative bleeding. Clinical trial registration:
www.ClinicalTrials.gov , NCT02738190.
PMID- 28510742
TI - Drug safety in paediatric anaesthesia.
AB - Life-threatening drug errors are more common in children than in adults. This is
likely to be because of their variations in age and weight, combined with the
occasional exposure of most anaesthetists to paediatric patients. Drug
administration in anaesthesia is mostly undertaken by a single operator and thus
represents a potentially greater risk compared with other areas of medicine. This
increased risk is believed to be offset by anaesthetists working with only a
limited number of drugs on a very frequent and repetitive basis. However, high
rates of errors continue to be reported. Paediatric anaesthesia practice requires
individual age- and weight-specific drug dose calculations and is therefore
without a 'familiar' or 'usual' dose. The aim of this narrative systematic review
of existing recommendations and current evidence of preventive strategies is to
identify measures to enhance the safety and quality of drug administration in
paediatric anaesthesia. This review collates and grades the evidence of such
interventions and recommendations and assesses their feasibility. Most highly
effective available measures require low or limited costs and labour. The
presented solutions should, therefore, achieve a high level of acceptance and
contribute significantly to safety and quality of care in paediatric anaesthesia.
PMID- 28510743
TI - Critical airways, critical language.
PMID- 28510744
TI - It's not about the bike: enhancing oxygen delivery.
PMID- 28510745
TI - Neural network imaging to characterize brain injury in cardiac procedures: the
emerging utility of connectomics.
AB - Cognitive dysfunction is a poorly understood but potentially devastating
complication of cardiac surgery. Clinically meaningful assessment of cognitive
changes after surgery is problematic because of the absence of a means to obtain
reproducible, objective, and quantitative measures of the neural disturbances
that cause altered brain function. By using both structural and functional
connectivity magnetic resonance imaging data to construct a map of the inter
regional connections within the brain, connectomics has the potential to increase
the specificity and sensitivity of perioperative neurological assessment,
permitting rational individualized assessment and improvement of surgical
techniques.
PMID- 28510746
TI - Engaging in risky business: is it time to rethink risk tolerance in anaesthesia?
PMID- 28510747
TI - 'Failed supraglottic airway': an algorithm for suboptimally placed supraglottic
airway devices based on videolaryngoscopy.
PMID- 28510748
TI - Volatile anaesthetics and organ protection in kidney transplantation: finally, a
randomized controlled trial!
PMID- 28510749
TI - Dead or dying? Pulseless electrical activity during trauma resuscitation.
PMID- 28510750
TI - Medication errors in paediatric anaesthesia: the hidden part of the iceberg.
PMID- 28510751
TI - Anaesthetic considerations for hybrid atrial fibrillation surgery.
PMID- 28510752
TI - Real-time ultrasound-guided paramedian spinal anaesthesia: evaluation of the
efficacy and the success rate of single needle pass.
PMID- 28510753
TI - A different use of visual analytic techniques in anaesthetics.
PMID- 28510754
TI - The diagnostic challenge of a vitamin K antagonist with dabigatran use triggering
massive intracranial haemorrhage.
PMID- 28510755
TI - Suturing central venous catheters.
PMID- 28510756
TI - Classification of videolaryngoscopes is crucial.
PMID- 28510757
TI - An unusual sidestream capnogram.
PMID- 28510758
TI - Reply-stopping antithrombotics during regional anaesthesia and eye surgery:
crying wolf?
PMID- 28510760
TI - What factors hinder the decision-making process for women with cancer and
contemplating fertility preservation treatment?
AB - BACKGROUND: Although fertility preservation (FP) treatment options have
increased, the existing evidence suggests that many women with cancer do not feel
well supported in making these decisions, but find them stressful and complex and
fail to take up fertility care at this crucial time. Whilst existing reviews have
all made important contributions to our understanding of the FP decision-making
process, none of them examine solely and specifically these processes for women
of reproductive age with a diagnosis of any cancer, leaving a gap in the
knowledge base. Given the expectation that care is patient-centred, our review
aims to address this gap which may be of help to those managing patients
struggling to make difficult decisions in the often brief period before
potentially sterilizing cancer treatment is started. OBJECTIVE AND RATIONALE:
Underpinning this narrative review was the question 'What factors hinder the
decision-making process for women with any cancer and contemplating FP
treatment?' Our objectives were to (i) assess and summarize this existing
literature, (ii) identify the factors that hinder this decision-making process,
(iii) explore to what extent these factors may differ for women choosing
different methods of FP and (iv) make recommendations for service delivery and
future research. SEARCH METHODS: A systematic search of the medical and social
science literature from the 1 January 2005 up to the end of January 2016 was
carried out using three electronic databases (Web of Science (PubMed), Ovid SP
Medline and CINAHL via Ebsco). Included in the review were quantitative,
qualitative and mixed-method studies. Reference lists of relevant papers were
also hand searched. From the 983 papers identified, 46 papers were included.
Quality assessment was undertaken using the Mixed Methods Appraisal Tool and
thematic analysis was used to analyse the data. OUTCOMES: From the analysis, 6
key themes with 15 sub-themes emerged: (i) fertility information provision (lack
of information, timing of the information, patient-provider communication); (ii)
fear concerning the perceived risks associated with pursuing FP (delaying cancer
treatment, aggravating a hormone positive cancer and consequences of a future
pregnancy); (iii) non-referral from oncology (personal situation, having a
hormone positive cancer, FP not a priority and transition between service
issues); (iv) the dilemma (in survival mode, whether to prioritize one treatment
over another); (v) personal situation (parity, relationship status) and (iv)
costs (financial concerns). WIDER IMPLICATIONS: This review has found that a wide
range of internal and external factors impact the FP decision-making process. Key
external issues related to current service delivery such as the provision and
timing of FP information, and lack of referral from oncology to the fertility
clinic. However, internal issues such as women's fears concerning the perceived
risks associated with pursuing FP also hindered decision-making but these 'risks'
were typically overestimated and non-evidence based. These findings suggest that
the implementation of a range of decision support interventions may be of benefit
within the clinical care pathway of FP and cancer. Women would benefit from the
provision of more evidence-based FP information, ideally received at cancer
diagnosis, in advance of seeing a fertility specialist, for example through the
implementation of patient decision aids. Healthcare professionals in both
oncology and fertility services may also benefit from the implementation of
training programmes and educational tools targeted at improving the communication
skills needed to improve collaborative decision-making and deliver care that is
patient-centred. Exploration of the current barriers, both intellectual and
practical, that prevent some patients from accepting FP will help care providers
to do better for their patients in the future. Finally, the extent to which a
poorer prognosis and moral, ethical and religious beliefs influence the FP
decision-making process also warrant further research.
PMID- 28510759
TI - An intact Mcm10 coiled-coil interaction surface is important for origin melting,
helicase assembly and the recruitment of Pol-alpha to Mcm2-7.
AB - Mcm10 is an essential eukaryotic factor required for DNA replication. The
replication fork helicase is composed of Cdc45, Mcm2-7 and GINS (CMG). DDK is an
S-phase-specific kinase required for replication initiation, and the DNA primase
polymerase in eukaryotes is pol alpha. Mcm10 forms oligomers in vitro, mediated
by the coiled-coil domain at the N-terminal region of the protein. We
characterized an Mcm10 mutant at the N-terminal Domain (NTD), Mcm10-4A, defective
for self-interaction. We found that the Mcm10-4A mutant was defective for
stimulating DDK phosphorylation of Mcm2, binding to eighty-nucleotide ssDNA, and
recruiting pol alpha to Mcm2-7 in vitro. Expression of wild-type levels of mcm10
4A resulted in severe growth and DNA replication defects in budding yeast cells,
with diminished DDK phosphorylation of Mcm2. We then expressed the mcm10-4A in
mcm5-bob1 mutant cells to bypass the defects mediated by diminished stimulation
of DDK phosphorylation of Mcm2. Expression of wild-type levels of mcm10-4A in
mcm5-bob1 mutant cells resulted in severe growth and DNA replication defects,
along with diminished RPA signal at replication origins. We also detected
diminished GINS and pol-alpha recruitment to the Mcm2-7 complex. We conclude that
an intact Mcm10 coiled-coil interaction surface is important for origin melting,
helicase assembly, and the recruitment of pol alpha to Mcm2-7.
PMID- 28510761
TI - The diversity of CO2-concentrating mechanisms in marine diatoms as inferred from
their genetic content.
AB - Marine diatoms are one of the most ecologically significant primary producers in
the ocean. Most diatoms use a CO2-concentrating mechanism (CCM) to overcome the
scarcity of CO2 in the ocean and limitations of the carbon-fixing enzyme Rubisco.
However, the CCMs in model diatoms differ substantially in their genetic make-up
and structural organization. To assess the extent of CCM diversity in marine
diatoms more generally, we analyzed genome and transcriptome data from 31 diatom
strains to identify putative CCM genes, examine the overall CCM architecture, and
study CCM development in the context of the evolutionary history of these
diatoms. Key CCM genes [carbonic anhydrases (CAs) and solute carrier 4 (SLC4)
bicarbonate transporters] identified in the diatoms were placed into groups of
likely orthologs by sequence similarity (OrthoMCL) and phylogenetic methods.
These analyses indicated that diatoms seem to share similar HCO3- transporters,
but possess a variety of CAs that have either undergone extensive diversification
within the diatom lineage or have been acquired through horizontal gene transfer.
Hierarchical clustering of the diatom species based on their CCM gene content
suggests that CCM development is largely congruent with evolution of diatom
species, despite some notable differences in CCM genes even among closely related
species.
PMID- 28510762
TI - Physician burnout, work engagement and the quality of patient care.
AB - Background: Research suggests that burnout in physicians is associated with
poorer patient care, but evidence is inconclusive. More recently, the concept of
work engagement has emerged (i.e. the beneficial counterpart of burnout) and has
been associated with better care. Evidence remains markedly sparse however. Aims:
To examine the associations of burnout and work engagement with physicians' self
perceived quality of care. Methods: We drew on cross-sectional data from
physicians in Germany. We used a six-item version of the Maslach Burnout
Inventory measuring exhaustion and depersonalization. We employed the nine-item
Utrecht Work Engagement Scale to assess work engagement and its subcomponents:
vigour, dedication and absorption. We measured physicians' own perceptions of
their quality of care by a six-item instrument covering practices and attitudes.
We used continuous and categorized dependent and independent variables in linear
and logistic regression analyses. Results: There were 416 participants. In
multivariable linear regression analyses, increasing burnout total scores were
associated with poorer perceived quality of care [unstandardized regression
coefficient (b) = 0.45, 95% confidence interval (CI) 0.37, 0.54]. This
association was stronger for depersonalization (b = 0.37, 95% CI 0.29, 0.44) than
for exhaustion (b = 0.26, 95% CI 0.18, 0.33). Increasing work engagement was
associated with higher perceived quality care (b for the total score = -0.20, 95%
CI -0.28, -0.11). This was confirmed for each subcomponent with stronger
associations for vigour (b = -0.21, 95% CI -0.29, -0.13) and dedication (b =
0.16, 95% CI -0.24, -0.09) than for absorption (b = -0.12, 95% CI -0.20, -0.04).
Logistic regression analyses yielded comparable results. Conclusions: Physician
burnout was associated with self-perceived poorer patient care, while work
engagement related to self-reported better care. Studies are needed to
corroborate these findings, particularly for work engagement.
PMID- 28510763
TI - Reply to: "Periodic Limb Movements During Sleep and White Matter MRI
Hyperintensity in Minor Stroke or TIA".
PMID- 28510764
TI - Periodic Limb Movements During Sleep and White Matter MRI Hyperintensity in Minor
Stroke or TIA.
PMID- 28510765
TI - Research Priorities in the Area of Sleep/Circadian Rhythm and Aging Research:
Commentary on "Report and Research Agenda of the American Geriatrics Society and
National Institute on Aging Bedside-to-Bench Conference on Sleep, Circadian
Rhythms, and Aging: New Avenues for Improving Brain Health, Physical Health, and
Functioning".
PMID- 28510768
TI - Corrigenda.
PMID- 28510767
TI - Corrigenda.
PMID- 28510766
TI - Detection of 3,3'-Dichlorobiphenyl in Human Maternal Plasma and Its Effects on
Axonal and Dendritic Growth in Primary Rat Neurons.
AB - 3,3'-Dichlorobiphenyl (PCB 11), a byproduct of pigment production, is
increasingly detected in environmental samples. While more highly chlorinated PCB
congeners are known developmental neurotoxicants, nothing is known about the
potential developmental neurotoxicity of PCB 11. To address this critical data
gap, we measured PCB 11 levels in human maternal plasma and quantified the
effects of PCB 11 and its major metabolites on morphometric parameters of
neuronal connectivity in cultured primary neurons. Mass spectrometry analyses of
plasma from 241 pregnant women enrolled in the MARBLES study (University of
California, Davis) detected PCB 11 in all samples at concentrations ranging from
0.005 to 1.717 ng/ml. Morphometric analyses of primary neuron-glia co-cultures
dissociated from the neocortices or hippocampi of neonatal Sprague Dawley rats
exposed to vehicle or concentrations ranging from 1 attamolar (aM) to 1
micromolar (uM) of PCB 11, OH-PCB 11, or PCB 11 sulfate indicated that PCB 11 and
both metabolites significantly increased axonal and dendritic growth in cortical
and hippocampal pyramidal neurons. PCB 11 significantly altered neuronal
morphogenesis at concentrations as low as 1 femtomolar (fM), which is ~0.22
ng/ml. These data suggest the potential for the developing human brain to be
exposed to PCB 11, and demonstrate that environmentally relevant levels of PCB 11
alter axonal and dendritic growth in neuronal cell types critically involved in
cognitive and higher-order behaviors. These findings identify PCB 11 as a
potential environmental risk factor for adverse neurodevelopmental outcomes in
humans.
PMID- 28510769
TI - Comparison of Objective and Subjective Techniques of Strabismus Measurement in
Adults With Normal Retinal Correspondence.
AB - PURPOSE: Accurate measurement of strabismus is vital to proper diagnosis and
treatment. Objective and subjective measurement techniques can be used. The
authors hypothesized that subjective measurement techniques would measure larger
deviations than objective ones. METHODS: Adults with strabismus, visual acuity
greater than 20/50 in each eye, and normal retinal correspondence were measured
in primary gaze at distance and near using the alternate prism and cover test and
the red glass test. RESULTS: Seventy-three patients were prospectively enrolled.
Objective mean deviations were 9.1 (distance horizontal), 5.1 (distance
vertical), 10.0 (near horizontal), and 2.6 (near vertical) prism diopters (PD).
Subjective mean deviations were 10.2 (distance horizontal), 6.8 (distance
vertical), 12.2 (near horizontal), and 3.2 (near vertical) PD. Subjective
measurements were larger by a statistically significant margin and were more
likely to show the presence of a vertical deviation not measured objectively (19
occurrences vs 2 at near, P = .008; 15 occurrences vs 0 at distance, P = .004).
The measured deviations were within 5 PD horizontally and 3 PD vertically most of
the time (range: 66.7% to 83.6%). CONCLUSIONS: The red glass test was more likely
to measure a larger deviation at distance and near and to identify a vertical
deviation not seen objectively at both distance and near. The mean difference
between the tests was usually not large enough to affect surgical treatment, but
could potentially result in different amounts of prescribed prism for patients
treated optically. [J Pediatr Ophthalmol Strabismus. 2017;54(4):216-220.].
PMID- 28510770
TI - Inferior Oblique Overaction: Anterior Transposition Versus Myectomy.
AB - PURPOSE: To compare the efficacy of inferior oblique myectomy and anterior
transposition for correcting inferior oblique overaction (IOOA). METHODS: This
retrospective study was conducted on 56 patients with IOOA who had either
myectomy or anterior transposition of the inferior oblique muscle from 2010 to
2015. The authors compared preoperative and postoperative inferior oblique muscle
function grading (-4 to +4) as the main outcome measure and vertical and
horizontal deviation, dissociated vertical deviation (DVD), and A- and V-pattern
between the two surgical groups as secondary outcomes. RESULTS: A total of 99
eyes of 56 patients with a mean age of 5.9 +/- 6.5 years were included (47 eyes
in the myectomy group and 52 eyes in the anterior transposition group). There
were no differences in preoperative best corrected visual acuity, amblyopia,
spherical equivalent, and primary versus secondary IOOA between the two groups.
Both surgical procedures were effective in reducing IOOA and satisfactory results
were similar between the two groups: 61.7% and 67.3% in the myectomy and anterior
transposition groups, respectively (P = .56). After adjustment for the
preoperative DVD, there was no statistically significant difference between the
two groups postoperatively. The preoperative hypertropia was 6 to 14 and 6 to 18
prism diopters (PD) in the myectomy and anterior transposition groups,
respectively. After surgery, no patient had a vertical deviation greater than 5
PD. CONCLUSIONS: Both the inferior oblique myectomy and anterior transposition
procedures are effective in reducing IOOA with similar satisfactory results. DVD
and hypertropia were also corrected similarly by these two surgical procedures.
[J Pediatr Ophthalmol Strabismus. 2017;54(4):232-237.].
PMID- 28510771
TI - Inability of Open-Field Autorefraction to Eliminate Accommodation in
Preschoolers.
AB - PURPOSE: To evaluate the effectiveness of the Shin-Nippon NVision-K 5001
autorefractometer (Rexxam Co. Ltd., Osaka, Japan) (also branded as the Grand
Seiko WR-5100K; Grand Seiko Co. Ltd., Hiroshima, Japan) based on the open-field
refractometry principle in refractive measurements of preschool children and to
determine its ability to eliminate accommodation adequately. METHODS: The
refractive results of 114 preschool children who presented to the ophthalmology
outpatient department for screening were evaluated. The measurements were
obtained before and after cycloplegia with the Shin-Nippon NVision-K 5001
autorefractometer and after cycloplegia with retinoscopy, which is the gold
standard. The results underwent vectorial transformation to produce the spherical
equivalent (M) and two Jackson cross-cylinder (J0 and J45) values. All results
were then subjected to statistical analysis. The difference between the
measurements was evaluated with repeated measures analysis of variance. RESULTS:
Included in the study were 106 preschool children (51 boys and 55 girls). The
mean age was 5.3 +/- 0.9 years (range: 3 to 6 years). Although statistically
significantly more myopic results were obtained with non-cycloplegic measurements
using the Shin-Nippon NVision-K 5001 autorefractometer (P < .001), no difference
was observed in cylindrical values (P > .05). Cycloplegic J0 measurements were
significantly lower (P < .001), but no difference was found between J45 values
before and after cycloplegia (P > .05). CONCLUSIONS: The Shin-Nippon NVision-K
5001/Grand Seiko WR-5100K open-field autorefractometer seems to be inadequate in
eliminating accommodation in childhood. Measurements under cycloplegia continue
to be the best method to ensure accurate results. [J Pediatr Ophthalmol
Strabismus. 2017;54(5):311-318.].
PMID- 28510772
TI - Prevalence, Incidence, and Risk Factors for the Development of Glaucoma in
Patients With Aniridia.
AB - PURPOSE: To assess the prevalence, incidence, and risk factors for the
development of glaucoma in patients with aniridia. METHODS: Retrospective
analysis of case records of patients diagnosed as having congenital aniridia
between January 1986 and December 2011 was performed. Patients with a follow-up
of more than 12 months were included. RESULTS: Ninety-one patients (180 eyes)
with the diagnosis of aniridia were identified from the case records. Two eyes
were excluded from the final analysis; one had developed phthisis and the other
had been enucleated. Seventy-four patients (81.3%) were younger than 18 years at
initial presentation. The prevalence of glaucoma at presentation was 28.8%, which
could be further categorized as ocular hypertension in 19 eyes (10.5%) and
glaucoma in 33 eyes (18.3%). Thirty-one eyes (28.4%) developed elevated
intraocular pressure (IOP) during the follow-up period: ocular hypertension in 23
eyes (17.9%) and glaucoma in 8 eyes (6.25%). The mean IOP at the time of
diagnosis was 33.9 +/- 8.6 mm Hg (range: 24 to 60 mm Hg). The mean duration of
follow-up was 8.1 +/- 5.7 years (range: 1 to 28 years). The cumulative
probability of developing elevated IOP was 4% at the end of 8 years of follow-up;
this increased to 88% at the end of 28 years of follow-up. Univariate logistic
regression analysis identified higher baseline IOP (odds ratio [OR]: 1.2; 95%
confidence interval [CI]: 1.2 to 1.4) and limbal stem cell deficiency (OR: 2.8;
95% CI: 1.4 to 5.6) as significant risk factors for the development of elevated
IOP. Higher baseline IOP remained significant on multivariate analysis (OR: 1.2;
95% CI: 1.2 to 1.4). CONCLUSIONS: Glaucoma occurs in a substantial proportion of
patients with aniridia. Eyes with increased IOP at baseline are at a higher risk.
[J Pediatr Ophthalmol Strabismus. 2017;54(4):250-255.].
PMID- 28510773
TI - Evaluation of the Role of Monocular Video Game Play as an Adjuvant to Occlusion
Therapy in the Management of Anisometropic Amblyopia.
AB - PURPOSE: To evaluate the role of monocular video game play as an adjuvant to
occlusion therapy in the treatment of anisometropic amblyopia. METHODS: In a
prospective randomized study design, 68 children with ages ranging from 6 to 14
years who had anisometropic amblyopia with a best corrected visual acuity (BCVA)
in the amblyopic eye of better than 6/36 and worse than 6/12 and no manifest
strabismus were recruited. They were randomly allocated into two groups: 34
children received 1 hour per day of video game play for the first month plus 6
hours per day of occlusion therapy (video game and occlusion group) and 34
children received 6 hours per day of occlusion therapy alone (occlusion only
group). Patients were then evaluated at baseline and 1 and 3 months after
treatment for BCVA, stereoacuity, and contrast sensitivity. RESULTS: In the video
game and occlusion group, BCVA improved from 0.61 +/- 0.12 logarithm of the
minimum angle of resolution (logMAR) at baseline to 0.51 +/- 0.14 logMAR (P =
.001) at 1 month and 0.40 +/- 0.15 logMAR (P = .001) at 3 months. In the
occlusion only group, BCVA improved from 0.65 +/- 0.09 logMAR at baseline to 0.60
+/- 0.10 logMAR (P = .001) at 1 month and 0.48 +/- 0.10 logMAR (P = .001) at 3
months. There was significantly more improvement in the video game and occlusion
group compared to the occlusion only group (P = .003 at 1 month and P = .027 at 3
months). CONCLUSIONS: Video game play plus occlusion therapy enhances the visual
recovery in anisometropic amblyopia. [J Pediatr Ophthalmol Strabismus.
2017;54(4):244-249.].
PMID- 28510774
TI - Combined Surgery for Simultaneous Treatment of Congenital Ptosis and Coexisting
Strabismus.
AB - PURPOSE: To evaluate the clinical outcomes of single-stage surgery for treatment
of patients with congenital ptosis and coexisting strabismus. METHODS: A
retrospective analysis was performed on 10 patients (17 eyes) with congenital
ptosis and coexisting strabismus. Patients were treated with levator resection or
frontalis suspension for ptosis and ocular muscle surgery for strabismus,
performed as a single-stage procedure. Levator resection was performed in 9
patients (15 eyes) and frontalis muscle flap suspension was performed in 1
patient (2 eyes) with blepharophimosis. Seven patients (11 eyes) simultaneously
underwent exotropia correction, and inferior oblique myectomy was performed in 3
patients (3 eyes) with congenital superior oblique palsy. RESULTS: Satisfactory
efficacy of single-stage surgery for correction of congenital ptosis and
coexisting strabismus was achieved without complications. CONCLUSIONS:
Comprehensive preoperative examination is vital to determine the appropriate
diagnosis and guide surgical decision-making. Single-stage surgery for congenital
ptosis and coexisting strabismus is effective and a shortened treatment period is
beneficial to patients. [J Pediatr Ophthalmol Strabismus. 2017;54(5):288-294.].
PMID- 28510775
TI - Progression of High Anisometropia in Children.
AB - PURPOSE: To investigate the onset and rate of progression of high anisometropia
in myopic children younger than 13 years. METHODS: A retrospective study was
performed on children with anisometropia younger than 13 years with myopia of
more than 4.00 diopters (D) in the more ametropic eye and a difference in
spherical equivalent refraction of 4.00 D between both eyes. All children had a
complete ophthalmologic examination, including measurement of visual acuity and
cycloplegic refraction every 3 to 6 months for at least 5 years. Change in the
spherical equivalent and the cylindrical error for both eyes and changes in the
difference in spherical equivalent refraction between both eyes were calculated
for each patient at each visit. Linear, polynomial, logarithmic, and exponential
fitting models were tested for both eyes and for the anisometropic difference
between both eyes. The regression line with the greatest R2 value was considered
best fit. RESULTS: Sixty-three patients fulfilled the inclusion criteria. The
more ametropic eye grew in a regular fashion during the first 2 years of life,
followed by a rapid decrease in the rate of growth to become almost stable after
4 years of age. The increase in myopia best fit a third-degree polynomial (cubic)
model (R2 = 0.98). The less ametropic eye showed only a small increase in myopia
during the follow-up period. The anisometropic difference between both eyes
increased gradually during the first 2 years, then remained stable. CONCLUSIONS:
High anisometropic myopia progresses rapidly in the first few years of life
before becoming stable. [J Pediatr Ophthalmol Strabismus. 2017;54(5):282-286.].
PMID- 28510776
TI - Patient Characteristics and Surgical Approach Impacting Simultaneous to Alternate
Prism Cover Test Disparity After Exotropia Surgery: A Quantitative Look at the
Difference in Motor Outcomes.
AB - PURPOSE: To investigate the relationship between simultaneous prism and cover
test (SPCT) and alternate prism and cover test (APCT) outcomes after exotropia
surgery, and to identify characteristics associated with significant disparity
between them. METHODS: Review of sensorimotor outcomes 2 to 6 months after
exotropia surgery identified patients with alignment documented by both SPCT and
APCT at the same examination. Two hundred seventy-four and 319 patients had both
measurements recorded at distance and near, respectively. Correlation between the
SPCT and APCT and range of APCT when the SPCT measurement was zero were
determined. Patient characteristics studied for association with a difference
between the SPCT and APCT exceeding known APCT test-retest variability included
age, visual acuity, fusion, intermittency, pattern, preoperative and
postoperative angle, and treatment with or without medial rectus resection.
RESULTS: SPCT and APCT outcomes were strongly correlated (P < .001),
significantly different (P < .001), and linearly related. The percentage of
patients who were orthotropic (SPCT = 0) was 76% at distance and 80% at near.
Misalignment of 10 prism diopters (PD) or less by the APCT was present in 92% of
orthotropic patients at distance and 84% at near. Surgery without medial rectus
resection (P = .015), larger preoperative angle (P = .003), intermittent
exotropia (P = .028), and postoperative exotropia rather than esotropia (P <
.001) were associated with a significant SPCT-APCT difference. CONCLUSIONS:
Although a greater postoperative SPCT-APCT disparity was confirmed for patients
with intermittent exotropia, it also independently associated with a larger
preoperative deviation and surgery without medial rectus resection. Performing
medial rectus resection, a surgeon's prerogative, provides more apparently
consistent postoperative alignment characterized by less SPCT-APCT disparity. [J
Pediatr Ophthalmol Strabismus. 2017;54(4):222-230.].
PMID- 28510777
TI - Anatomical Characterization of the Nasolacrimal Canal Based on Computed
Tomography in Children With Complex Congenital Nasolacrimal Duct Obstruction.
AB - PURPOSE: To characterize anatomical variations of the nasolacrimal canal in
patients with complex congenital nasolacrimal duct obstruction. METHODS:
Retrospective case series of 25 children with congenital nasolacrimal duct
obstruction. All children had failed probings and were examined by computed
tomography. An analysis of imaging data is presented. RESULTS: Anomalous
development of the nasolacrimal canal was confirmed on computed tomography. Two
main types of malformations were observed: fundamental (20 patients) and special
(5 patients). In the fundamental type, the upper portion of the nasolacrimal
canal was relatively normal and became significantly stenotic, or even atretic,
at the middle and terminal segments. In the special type, the upper portion of
the nasolacrimal duct was malformed. Only the special type showed an association
with systemic abnormalities. In patients with unilateral fundamental type
malformation (11 patients), the transverse and anteroposterior diameters of the
upper segment of the nasolacrimal canal on the affected side were significantly
larger than that of the normal side (P = .000). The height of the nasolacrimal
canal on the normal side was significantly larger than that of the affected side
(P = .000). CONCLUSION: Computed tomography is useful for delineation of
anatomical characteristics of the nasolacrimal canal and to diagnose nasolacrimal
canal malformation. Malformed nasolacrimal canals are of two main types:
fundamental and special. Hydrostatic pressure in the lacrimal duct appears to the
underlying mechanism as enlargement of the nasolacrimal canal in the unilateral
fundamental type. [J Pediatr Ophthalmol Strabismus. 2017;54(4):238-243.].
PMID- 28510780
TI - Design and Testing of a New Diatom-Based Index for Heavy Metal Pollution.
AB - The Tinto and Odiel river basins (SW Spain) are known worldwide for their unique
water characteristics. Such uniqueness is a consequence of their flow through the
Iberian Pyrite Belt (an area rich in metal sulphides) and the mining activities
in the basins. A process of sulphide oxidation occurs in this region, which
acidifies the water and increases the amount of heavy metals in it. As a result,
the rivers suffer the so-called "acid mine drainage" (AMD). Traditional biotic
diatom-based indexes (IPS, IBD, EPI-D, etc.) do not take into account the
pollution caused by AMD. The purpose of this paper is to develop a new diatom
based index which can serve as a useful and quick monitoring tool. Such tool must
reflect the level of AMD while being user friendly. We present the development
and validation of the ICM (Indice de Contaminacion por Metales or Metal Pollution
Index). ICM demonstrated to meet successfully the above criteria and, therefore,
can assess water quality in the Tinto and Odiel Rivers. In addition, ICM was
applied with satisfactory results in the Guadiamar River (SW Spain), which was
subjected to AMD too. Thus, we propose to make use of it in any other basin with
the same type of pollution.
PMID- 28510779
TI - Modelling foetal exposure to maternal smoking using hepatoblasts from pluripotent
stem cells.
AB - The liver is a dynamic organ which is both multifunctional and highly
regenerative. A major role of the liver is to process both endo and xenobiotics.
Cigarettes are an example of a legal and widely used drug which can cause major
health problems for adults and constitute a particular risk to the foetus, if the
mother smokes during pregnancy. Cigarette smoke contains a complex mixture of
thousands of different xenobiotics, including nicotine and polycyclic aromatic
hydrocarbons. These affect foetal development in a sex-specific manner, inducing
sex-dependant molecular responses in different organs. To date, the effect of
maternal smoking on the foetal liver has been studied in vitro using cell lines,
primary tissue and animal models. While these models have proven to be useful,
poor cell phenotype, tissue scarcity, batch-to-batch variation and species
differences have led to difficulties in data extrapolation toward human
development. Therefore, in this study we have employed hepatoblasts, derived from
pluripotent stem cells, to model the effects of xenobiotics from cigarette smoke
on human hepatocyte development. Highly pure hepatocyte populations (>90%) were
produced in vitro and exposed to factors present in cigarette smoke. Analysis of
ATP levels revealed that, independent of the sex, the majority of smoking
derivatives tested individually did not deplete ATP levels below 50%. However,
following exposure to a cocktail of smoking derivatives, ATP production fell
below 50% in a sex-dependent manner. This was paralleled by a loss metabolic
activity and secretory ability in both female and male hepatocytes.
Interestingly, cell depletion was less pronounced in female hepatocytes, whereas
caspase activation was ~twofold greater, indicating sex differences in cell death
upon exposure to the smoking derivatives tested.
PMID- 28510783
TI - Transcranial Doppler monitoring guided by cranial two-dimensional
ultrasonography.
PMID- 28510781
TI - 5-Azacytidine mediated reactivation of silenced transgenes in potato (Solanum
tuberosum) at the whole plant level.
AB - KEY MESSAGE: Transient 5-azacytidine treatment of leaf explants from potato
plants with transcriptionally silenced transgenes allows de novo regeneration of
plants with restored transgene expression at the whole plant level. Transgenes
introduced into plant genomes frequently become silenced either at the
transcriptional or the posttranscriptional level. Transcriptional silencing is
usually associated with DNA methylation in the promoter region. Treatments with
inhibitors of maintenance DNA methylation were previously shown to allow
reactivation of transcriptionally silenced transgenes in single cells or tissues,
but not at the whole plant level. Here we analyzed the effect of DNA methylation
inhibitor 5-azacytidine (AzaC) on the expression of two silenced reporter genes
encoding green fluorescent protein (GFP) and neomycin phosphotransferase (NPTII)
in potato plants. Whereas no obvious reactivation was observed in AzaC-treated
stem cuttings, transient treatment of leaf segments with 10 MUM AzaC and
subsequent de novo regeneration of shoots on the selective medium with kanamycin
resulted in the production of whole plants with clearly reactivated expression of
previously silenced transgenes. Reactivation of nptII expression was accompanied
by a decrease in cytosine methylation in the promoter region of the gene. Using
the plants with reactivated GFP expression, we found that re-silencing of this
transgene can be accidentally triggered by de novo regeneration. Thus, testing
the incidence of transgene silencing during de novo regeneration could be a
suitable procedure for negative selection of transgenic lines (insertion events)
which have an inclination to be silenced. Based on our analysis of non-specific
inhibitory effects of AzaC on growth of potato shoots in vitro, we estimated that
AzaC half-life in the culture media is approximately 2 days.
PMID- 28510782
TI - Memory-guided force control in healthy younger and older adults.
AB - Successful performance of a memory-guided motor task requires participants to
store and then recall an accurate representation of the motor goal. Further,
participants must monitor motor output to make adjustments in the absence of
visual feedback. The goal of this study was to examine memory-guided grip force
in healthy younger and older adults and compare it to performance on behavioral
tasks of working memory. Previous work demonstrates that healthy adults decrease
force output as a function of time when visual feedback is not available. We
hypothesized that older adults would decrease force output at a faster rate than
younger adults, due to age-related deficits in working memory. Two groups of
participants, younger adults (YA: N = 32, mean age 21.5 years) and older adults
(OA: N = 33, mean age 69.3 years), completed four 20-s trials of isometric force
with their index finger and thumb, equal to 25% of their maximum voluntary
contraction. In the full-vision condition, visual feedback was available for the
duration of the trial. In the no vision condition, visual feedback was removed
for the last 12 s of each trial. Participants were asked to maintain constant
force output in the absence of visual feedback. Participants also completed tasks
of word recall and recognition and visuospatial working memory. Counter to our
predictions, when visual feedback was removed, younger adults decreased force at
a faster rate compared to older adults and the rate of decay was not associated
with behavioral performance on tests of working memory.
PMID- 28510784
TI - Effects of acute and chronic hypoxia on acid-base regulation, hematology, ion,
and osmoregulation of juvenile American paddlefish.
AB - Despite the increasing prevalence of hypoxia in natural habitats occupied by the
American paddlefish, basal bony fish, and ram ventilator, information about its
response to hypoxia is scarce. To understand the physiological and biochemical
responses of juvenile paddlefish (~150 g) to acute (<24 h) and chronic hypoxia
(>=24 h), blood oxygen transport, blood acid-base balance, and metabolic stress
were evaluated under four different partial pressures of oxygen [pO2; normoxia
(148 mmHg), mild hypoxia (89 mmHg), moderate hypoxia (59 mmHg), and extreme
hypoxia (36 mmHg)], all at 21 degrees C. Arterial blood samples were collected
from paddlefish after they had been exposed to treatments for 0.25, 2, 6, 24, and
72 h, and analyzed for hematocrit, pO2, total oxygen content, oxygen saturation,
pCO2, pH, hemoglobin, Na+, K+, Ca2+, Cl-, glucose, and lactate. Mild hypoxia only
caused a reduction in blood pO2 and oxygen saturation. Both acute and chronic
moderate and extreme hypoxia caused a decrease in blood pH, pO2, total oxygen
content, plasma Na+, and Cl- at all time points. Acute moderate and extreme
hypoxia resulted in an increase in blood pCO2, plasma glucose, lactate, and
hematocrit. Chronic exposure to moderate hypoxia resulted in an increase in
plasma lactate, red blood cell count, and hemoglobin. This study shows that
paddlefish are able to physiologically compensate for mild hypoxia, but exhibit
secondary stress responses and are unable to return to homeostasis when exposed
to both acute and chronic moderate hypoxia, and die after 3-8 h of extreme
hypoxia.
PMID- 28510785
TI - The impact of leisure on mental health of Sardinian elderly from the 'blue zone':
evidence for ageing well.
AB - BACKGROUND: There has been scientific interest in the Sardinia population for a
number of years and for a variety of reasons, including its extreme longevity.
This is especially prevalent in the central-eastern region of the island, where a
blue zone region has been precisely delineated. AIMS: The present study examines
the influence of leisure activities on psychological well-being and depressive
symptoms in elderly individuals living in the blue zone region of inner Sardinia.
METHODS: Eighty-three participants were recruited according to strict inclusion
criteria to ensure their cognitive and residency status. Individuals were
assigned to either old (70-79 years) or very old (>=80 years) groups, and were
administered a test battery to determine their socio-demographic and lifestyle
characteristics, perceived physical health, and self-perceived well-being and
depressive symptoms. RESULTS: The primary findings indicate that participation in
leisure activities positively influenced both self-perceived well-being and
depressive symptoms. There was though, a differential impact on different sub
scales of well-being, and moreover, the overall pattern of results suggested
primarily an influence on mood states and/or emotion regulation. CONCLUSIONS: The
emerging psychological pattern of results about elders from the Sardinian blue
zone region provides insight for the promotion of successful ageing in late
adulthood.
PMID- 28510786
TI - The impact of frailty on noninvasive mechanical ventilation in elderly medical
intensive care unit patients.
AB - AIM: Many factors affecting noninvasive ventilation (NIV) in critically ill
patients have been reported in the literature, but there is no study about the
effect of frailty. With this study, the frailty prevalence was evaluated with two
different frailty scores among the NIV population of a medical intensive care
unit (ICU). Besides, the impact of frailty on NIV success and mortality and its
association with NIV application problems were evaluated. METHOD: A prospective
observational cohort study was performed on patients who were over 50 years of
age and assigned to NIV due to hypercapnic respiratory failure. For the
assessment of frailty, Clinical Frailty Scale (CFS) and The Edmonton Frailty
Scale (EFS) were used and the ones with CFS >=5 and EFS >=8 were considered as
fragile. The study population was classified and compared according to NIV
success, ICU outcome (discharge or exitus) and NIV application problems. RESULTS:
A total of 103 patients with the mean age of 73 +/- 11 years were included. The
incidence of frailty was 41% with CFS >=5 and 36% with EFS >=8. The NIV failure
occurred in 30 (29%) patients. Among them frailty and SOFA score was higher;
Glasgow Coma Scale (GCS) was lower. In multivariate analysis GCS (OR: 1.2, p:
0.042) and frailty with EFS (OR: 2.8, p: 0.027) were identified as independent
risk factors of NIV failure. Sixty-five (63%) patients had NIV application
problems and frailty was higher among them with both CFS and EFS (p < 0.05).
Mortality occurred in 18 (17%) patients; NIV failure and frailty according to CFS
were independent risk factors of mortality. CONCLUSION: The frailty is associated
with higher NIV application problems, failure and mortality risk in elderly ICU
patients. The CFS and EFS frailty scores can be used to predict NIV success and
outcomes in ICUs.
PMID- 28510788
TI - Effects of volatile organic compound ether on cell responses and gene expressions
in Arabidopsis.
AB - BACKGROUND: The volatile organic compound ether is widely used as an industrial
solvent and easily released to the environment. Our previous research indicated
that ether triggers reactive oxygen species (ROS) production and activates
ethylene biosynthetic genes and defense gene expressions in tomato. In the
present study, we investigated the effect of ether on cell responses and gene
expressions in Arabidopsis and compared the ROS and phytohormones produced in
Arabidopsis and tomato plants in response to different air pollutants (O3 vs.
ether). RESULTS: Ether induced the sequential production of superoxide anion and
hydrogen peroxide in Arabidopsis. Ether also triggered expressions of ethylene,
salicylic acid and jasmonic acid biosynthetic genes. The temporal expression
patterns of MAP kinase and protein phosphatase genes are in good accordance with
those of the ethylene and salicylic acid biosynthetic genes, suggesting that
induction of these phytohormone biosynthesis were through signaling pathways
including both phosphorylation and/or dephosphorylation. By contrast, expression
pattern of protein phosphatase PP2A3&4 coincided well with the expression of
jasmonic acid biosynthetic gene LOX4, suggesting that induction of jasmonic acid
biosynthesis is through PP2A3&4. However, the production of ROS and temporal
expression patterns of phytohormone biosynthetic genes in Arabidopsis in response
to ether were different from those to O3 and were different from those in tomato
as well. CONCLUSIONS: Different plants have different strategies to respond to
the same abiotic stress, and each plant species possesses its own unique
signaling pathways that regulate the responding process.
PMID- 28510787
TI - A phase II trial of arsenic trioxide and temozolomide in combination with
radiation therapy for patients with malignant gliomas.
AB - Standard treatment for GBM is radiation (RT) and temozolomide (TMZ). Arsenic
trioxide (ATO) is synergistic with RT based on several mechanisms of action
previously identified, however not tested herein. The MTD of ATO, RT and TMZ was
determined in a Phase I trial. We now present the combined Phase I/II data.
Patients with newly diagnosed malignant gliomas were eligible for treatment.
Patients were treated with RT (60 GY), TMZ (75 mg/m2 daily * 42 days) and ATO
0.20 mg/kg daily in week 1 then twice a week *5 weeks, after completing RT they
were treated with TMZ 5/28 for up to 12 months. MRIs were performed every 8
weeks. A total of 42 patients were enrolled in both the Phase I and II trials for
this study treatment. Of the 42 enrolled patients (24 M and 18 W) the median age
was 54 (24-80) and median KPS 90 (60-100). 28 patients had a GBM and 14 had
anaplastic glioma (AG). All patients completed RT/TMZ/ATO and went on to
maintenance TMZ. Median number of post RT cycles of TMZ was 4 (0-12). Median PFS
was 7 m for GBM and 75 m for AG and median OS was 17 m for GBM and NR for AG.
Best response was CR in 2, SD in 28, PR in 5 and PD in 7. There were no
unexpected adverse events. Grade 3 toxicities likely attributable to ATO included
prolonged Qtc (n = 1), elevated liver enzymes (n = 2 for ALT/n = 1 for AST) and
elevated bilirubin (n = 1). Adding ATO to RT and TMZ is feasible with no
increased side effects. The addition of arsenic did not improve overall survival
in the GBM patients as compared to historic data. MGMT status was analyzed in 20
of the 42 patients where tissue was available for retrieval and MGMT testing.
PMID- 28510789
TI - Pittosporum peridoticola (Pittosporaceae), a new ultramafic obligate species
restricted to Kinabalu Park (Sabah, Malaysia).
AB - BACKGROUND: Kinabalu Park, in Sabah (Malaysia) on Borneo Island, is renowned for
the exceptionally high plant diversity it protects, with at least 5000 plant
species enumerated to date. Discoveries of plant novelties continue to be made in
Sabah, especially on isolated ultramafic outcrops, including in the genus
Pittosporum (Pittosporaceae) with P. linearifolium from Bukit Hampuan on the
southern border of the Park, and P. silamense from Bukit Silam in Eastern Sabah,
both narrow endemics restricted to ultramafic soils. RESULTS: A distinctive new
species of Pittosporum (P. peridoticola J.B.Sugau and Ent, sp. nov.) was
discovered on Mount Tambuyukon in the north of Kinabalu Park during ecological
fieldwork. The diagnostic morphological characters of this taxon are discussed
and information about the habitat in which it grows is provided. The soil
chemistry in the rooting zone of P. peridoticola has high magnesium to calcium
quotients, high extractable nickel and manganese concentrations, but low
potassium and phosphorus concentrations, as is typical for ultramafic soils.
Analysis of foliar samples of various Pittosporum-species originating from
ultramafic and non-ultramafic soils showed a comparable foliar elemental
stoichiometry that is suggestive of 'Excluder-type' ecophysiology. CONCLUSION:
Pittosporum peridoticola is an ultramafic obligate species restricted to Kinabalu
Park with only two known populations within the boundaries of the protected area.
It is vulnerable to any future stochastic landscape disturbance events, such as
forest fires or severe droughts, and therefore its conservation status is 'Near
Threatened'.
PMID- 28510791
TI - Actephila alanbakeri (Phyllanthaceae): a new nickel hyperaccumulating plant
species from localised ultramafic outcrops in Sabah (Malaysia).
AB - The Malaysian state of Sabah on the Island of Borneo is emerging as a hotspot for
nickel hyperaccumulator species with at least 25 such species discovered to date.
New discoveries of the hyperaccumulation trait in described taxa, as well as
taxonomical novelties that are nickel hyperaccumulators, continue to be made.
Here we describe a new nickel hyperaccumulating species of Actephila
(Phyllanthaceae) originating from two known populations on ultramafic soils in
Sabah. The most characteristic feature of Actephila alanbakeri are its knobbly
fruits, but other diagnostic morphological characters are discussed and
information about its ecology and rhizosphere and plant tissue chemistry is
provided. This new species is one of the strongest known nickel hyperaccumulator
plants in Southeast Asia with up to 14,700 MUg g-1 (1.47 %) nickel in its leaves.
The occurrences of Actephila alanbakeri on just two sites, both of which lie
outside protected areas and are disturbed by recurring forest fires, combined
with the small total numbers of individuals, render this species Endangered (EN)
on the basis of IUCN Red List Criteria.
PMID- 28510790
TI - Leaf senescence induced by EGY1 defection was partially restored by glucose in
Arabidopsis thaliana.
AB - BACKGROUND: Ethylene-dependent gravitropism-deficient and yellow-green 1 (EGY1)
protein is required for chloroplast development and photosynthesis conduction.
The egy1 deletion mutants have a yellow-green phenotype and reduced granal
thylakoids. Furthermore, the yellow-green phenotype of egy1 mutants is more
obvious than that of wild-type (WT) plants with increasing leaf age, suggesting
an early senescence in the egy1 mutants. However, the relationship between EGY1
functions and leaf senescence still remains poorly understood. RESULTS: We
observed that egy1 mutant leaves were more yellow than those of WT (the same age)
in Arabidopsis thaliana. In accompany with this phenotype, leaf survival,
chlorophyll content, Fv/Fm and soluble protein content decreased, and ion leakage
increased significantly in egy1 mutants compared to WT plants. At molecular
level, the expressions of senescence-associated genes increased, and
photosynthesis genes decreased significantly in the mutants compared to those in
WT plants. Furthermore, after darkness treatment, the yellow-green phenotype of
egy1 mutants was more obvious than that of WT. These results indicate that the
loss-of-function of egy1 gene induces leaf senescence in A. thaliana. In
addition, our results showed that the yellow-green phenotype, chlorophyll content
and ion leakage of egy1 mutants was partially restored after exogenously applied
glucose for 5 weeks. At the same time, the expression of hexokinase 1 (HXK1)
and/or senescence-associated gene 12 (SAG12) in egy1 mutants growing on 2 %
glucose was lower than that in egy1 mutants without glucose. CONCLUSION: EGY1
defection induced leaf senescence and this senescence was partially restored by
glucose in A. thaliana.
PMID- 28510792
TI - A Systematic Review of Proinsulin-Secreting Pancreatic Neuroendocrine Tumors.
AB - BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are a heterogeneous group of
islet cell-derived neoplasms with a propensity toward hormone production. Among
PNETs, proinsulin-secreting tumors (proinsulinomas) are exceedingly rare. The
objective of this study is to collect and summarize the existing literature to
provide a comprehensive evaluation of this uncommon disease. METHODS: A
systematic review was performed to characterize the clinicopathologic features of
proinsulinoma. Using the electronic biomedical databases PubMed, Ovid Medline,
and Embase, 316 publications were screened for relevance of which 14 were
selected. We also present two patients with proinsulinoma treated at Yale New
Haven Hospital. RESULTS: Of the 16 patients included in the study, the mean age
was 56.8 and there was a 2:1 female predominance. The majority of patients
presented with symptomatic hypoglycemia with normal or low insulin levels. Median
tumor diameter was 1.2 cm and 80% were located in the body and tail of the
pancreas. Following resection, most patients had normalization of hormonal levels
without recurrence (75%; 12/16). CONCLUSION: Proinsulinomas are rare pancreatic
neuroendocrine tumors that have the potential to cause hypoglycemia. While
insulinomas and proinsulin-secreting tumors have many physiologic parallels,
these cases illustrate several key distinctions in their diagnosis and
management.
PMID- 28510793
TI - Cholecystectomy Following Idiopathic Pancreatitis: How Much to Look for Stones? :
Correspondence re Stevens, et al.: How Does Cholecystectomy Influence Recurrence
of Idiopathic Acute Pancreatitis? J Gastrointest Surg (2016) 20:1997-2001.
PMID- 28510796
TI - Focus on Bio-Ion Chemistry: Interactions of Biological Ions with Ions, Molecules,
Surfaces, Electrons, and Light, Honoring Scott A. McLuckey, Recipient of the 2016
ASMS Award for a Distinguished Contribution in Mass Spectrometry.
PMID- 28510794
TI - Long-Term Trends in Hematological and Nutritional Status After Gastrectomy for
Gastric Cancer.
AB - BACKGROUND: This study investigated long-term trends in hematological and
nutritional parameters after gastrectomy for gastric cancer and evaluated the
influence of the reconstruction type on these trends. METHODS: The medical
records of 558 patients who underwent curative gastrectomy with standard lymph
node dissection for stage I gastric cancer between January 2006 and December 2013
were reviewed. The hematological and nutritional parameters evaluated included
hemoglobin, ferritin, vitamin B12, total protein, albumin, total cholesterol,
triglyceride, and calcium. The patients were followed up for 6 months
postoperatively and then annually until death, cancer recurrence, or follow-up
loss. RESULTS: In the long term, ferritin and triglyceride gradually decreased
after gastrectomy, while the other parameters decreased slightly or were stable.
In the comparisons according to reconstruction type, the Roux-en-Y group had the
lowest levels of hemoglobin, ferritin, vitamin B12, total protein, albumin, and
total cholesterol beginning 6 months postoperatively compared with the Billroth I
and II groups. However, only ferritin and vitamin B12 had significant differences
in the 5-year cumulative incidences of deficiency/reduction according to the
reconstruction type, whereas albumin, triglyceride, total cholesterol, and
calcium did not. CONCLUSIONS: Although malabsorption and malnutrition are common
in patients after a gastrectomy, most nutritional parameters were stable or
decreased slightly in the long-term and were not markedly influenced by the
reconstruction type or extent of gastrectomy. Therefore, for more accurate
nutritional assessment after gastrectomy, multidirectional monitoring should be
considered rather than simply measuring biochemical parameters.
PMID- 28510795
TI - Liver Stiffness Assessed by Shear Wave Elastography Predicts Postoperative Liver
Failure in Patients with Hepatocellular Carcinoma.
AB - BACKGROUND: Cirrhosis increases a patient's risk of developing postoperative
liver failure (PLF). Liver stiffness (LS), assessed by two-dimensional shear wave
elastography (SWE), indicates liver fibrosis with high accuracy. Whether LS is
superior to portal hypertension (PHT) in predicting PLF remains to be studied.
METHODS: The study enrolled 280 patients who underwent hepatectomy for
hepatocellular carcinoma from July 2015 to July 2016. All patients received
preoperative assessments for LS, PHT, and serum markers of liver fibrosis in
addition to other clinicopathological tests. Risk factors for grade A and grade B
(or greater) PLF were subjected to univariate and multivariate analysis and
receiver operating characteristic curve analysis. RESULTS: Fifty-five patients
(19.6%) experienced PLF. The cutoff value of LS for predicting cirrhosis was 10.1
kPa. Multivariate analysis identified LS, hyaluronic acid, IV collagen, and the
presence of splenomegaly as independent predictors of PLF. The cutoff value of LS
for predicting PLF and grade B (or greater) PLF was 11.75 and 11.9 kPa,
respectively. LS was superior to PHT in predicting PLF or greater than grade B
PLF (0.72 vs. 0.60, 0.76 vs. 0.59, P < 0.05). CONCLUSION: LS measured by SWE can
predict risk of PLF with greater accuracy than PHT.
PMID- 28510797
TI - Influence of Morbid Obesity on the Pharmacokinetics of Morphine, Morphine-3
Glucuronide, and Morphine-6-Glucuronide.
AB - INTRODUCTION: Obesity is associated with many pathophysiological changes that may
result in altered drug metabolism. The aim of this study is to investigate the
influence of obesity on the pharmacokinetics of morphine, morphine-3-glucuronide
(M3G), and morphine-6-glucuronide (M6G) through a combined analysis in morbidly
obese patients and non-obese healthy volunteers. METHODS: In this analysis, data
from 20 morbidly obese patients [mean body mass index 49.9 kg/m2 (range 37.6-78.6
kg/m2) and weight 151.3 kg (range 112-251.9 kg)] and 20 healthy volunteers [mean
weight 70.6 kg (range 58-85 kg)] were included. Morbidly obese patients received
10 mg of intravenous (I.V.) morphine after gastric bypass surgery, with
additional morphine I.V. doses as needed. Healthy volunteers received an I.V.
bolus of morphine of 0.1 mg/kg followed by an infusion of 0.030 mg kg-1 h-1 for 1
h. Population pharmacokinetic modeling was performed using NONMEM 7.2. RESULTS:
In morbidly obese patients, elimination clearance of M3G and M6G was decreased
substantially compared with healthy volunteers (p < 0.001). Regarding
glucuronidation, only a slight decrease in the formation of M6G and a delay in
the formation of M3G was found (both p < 0.001). Obesity was also identified as a
covariate for the peripheral volume of distribution of morphine (p < 0.001).
CONCLUSION: Metabolism of morphine is not altered in morbidly obese patients.
However, decreased elimination of both M3G and M6G is evident, resulting in a
substantial increase in exposure to these two metabolites. A rational explanation
of this finding is that it results from alterations in membrane transporter
function and/or expression in the liver. ClinicalTrials.gov identifier:
NCT01097148.
PMID- 28510798
TI - Total Laparoscopic Management for Stage IV Colorectal Cancer Requiring
Multivisceral Resection.
AB - BACKGROUND: Surgical resection of all sites of disease, in combination with
effective systemic chemotherapy, offers the only potential chance for cure for
patients with stage IV colorectal cancer (CRC). Coordinated multistage resection
using a minimally invasive approach may provide optimal oncologic outcome while
potentially offering the benefit of decreased morbidity. PATIENT: A 66-year-old
women presented with transverse colon cancer and synchronous metastasis (CRLM) in
segment IV involving the middle hepatic vein and main left portal pedicle, as
well as the left adrenal gland. Due to favorable response to neoadjuvant
chemotherapy (FOLFOX/bevacizumab), the patient was considered for resection but
developed some obstructive symptoms from the primary tumor, necessitating re
coordination of treatment sequencing from the 'liver-first' approach. METHODS:
The first procedure combined laparoscopic subtotal colectomy (extracorporeal
anastomosis) with left adrenalectomy. After restaging, CRLM was removed
separately 2 months later via laparoscopic left hepatectomy extending beyond the
middle hepatic vein. Successful completion of the two procedures depended on
optimal patient/port positioning for the combined colon/adrenal surgery and the
second-stage liver resection. Postoperative lengths of stay were 4 and 3 days,
respectively, and were without complication. Adjuvant FOLFOX was initiated 21
days following liver surgery, and the patient has been disease-free for 36
months. CONCLUSION: This case illustrates the feasibility of the total
laparoscopic approach to multivisceral resection for synchronous stage IV CRC in
the context of a preplanned, staged multidisciplinary strategy. This approach may
offer optimal cancer management, including early return to systemic therapy,
shortened time intervals between stages, and minimal postoperative morbidity.1 -
3.
PMID- 28510799
TI - Practical Surgical Techniques for Lymphadenectomy Along the Right Recurrent
Laryngeal Nerve During Thoracoscopic Esophagectomy in the Prone Position.
AB - BACKGROUND: In esophageal squamous cell cancer (SCC), lymphadenectomy along the
right recurrent laryngeal nerve (RLN) is important for disease control. The
metastatic rate was 33% and the 5-year overall survival rate of these patients
was 33.3%,1 but the risk of RLN palsy increases.2 We reported a reliable new
method ('Pincers Maneuver')3 for lymphadenectomy along the right RLN during
thoracoscopic esophagectomy in the prone position (TEP), and hereby present our
video, aimed at providing a complete and safe dissection. METHOD: The 'Pincers
Maneuver' is performed for all resectable clinical stage IA-III lower, middle, or
upper thoracic esophageal SCCs. Patients above clinical stage IB were treated
with neoadjuvant chemotherapy. The concept of this procedure is to first
exfoliate the two-dimensional membrane (lateral pedicle), which includes the
right RLN, lymph nodes, and the primary esophageal artery, from the right side of
the trachea toward the neck. Improved mobility of the lateral pedicle, gained by
closing in from its inner and outer sides, enables easy lymphadenectomy along the
right RLN toward the right inferior thyroid artery. RESULTS: Using this method,
we performed 31 TEPs in 2016 at Kobe University Hospital. Median body mass index
was 23 kg/m2 (range 18-31). No right RLN palsy greater than Clavien-Dindo
classification grade I was observed. On average, 5.2 +/- 2.7 nodes were harvested
along the right RLN, with a 23% metastatic rate. CONCLUSIONS: Our method for
lymphadenectomy along the right RLN during TEP is safe and practical. It provides
sufficient lymph node dissection, and no right RLN palsy has been observed.
PMID- 28510800
TI - Structural modulation of gut microbiota in Bama minipigs in response to treatment
with a "growth-promoting agent", salbutamol.
AB - Even though salbutamol (SAL) had remarkable effects on the enhancement of growth
rate and carcass composition in different livestock species such as cattle, pigs,
sheep and poultry, it was banned as a growth promoter because of its adverse
effects on health. However, the specific mechanism by which salbutamol enhances
growth efficiency remains unknown. In this study, Bama pigs were randomly
allocated to receive salbutamol (5 mg/kg) for 30 or 60 days and were compared
with untreated pigs. Pigs treated with salbutamol demonstrated enhanced growth
rates and carcass composition; however, they showed deterioration in blood
biochemical indices and organ development. We hypothesized that salbutamol exerts
its effects by modulating the composition of the gut microbiota population. The
faecal microbiome of pigs was characterized via pyrosequencing of the bacterial
16S rRNA gene. The gut microbiota population analysis showed that salbutamol
caused shifts in the microbial composition of less abundant species. Redundancy
analysis indicated an increase in abundance of the phylum Bacteroidetes, class
Betaproteobacteria, family Christensenellaceae and genus Lactobacillus, and a
decreased ratio of the phylum Firmicutes, class Clostridia and genera
Ruminococcus, Blautia and Subdoligranulum. In conclusion, our study provided
circumstantial evidence that the various effects of salbutamol are caused by gut
microbiota modulation, and several potential candidates were identified for SAL
detection via the gut microbiota. Our findings provided new insights into the
roles of the gut microbiota during salbutamol treatment, and these findings will
aid in the screening of alternative strategies for animal health improvement and
production enhancement.
PMID- 28510801
TI - Characterization of an autotrophic bioreactor microbial consortium degrading
thiocyanate.
AB - Thiocyanate (SCN-) forms as a by-product of cyanidation during gold ore
processing and can be degraded by a variety of microorganisms utilizing it as an
energy, nitrogen, sulphur and/or carbon source. In complex consortia inhabiting
bioreactor systems, a range of metabolisms are sustained by SCN- degradation;
however, despite the addition or presence of labile carbon sources in most
bioreactor designs to date, autotrophic bacteria have been found to dominate key
metabolic functions. In this study, we cultured an autotrophic SCN--degrading
consortium directly from gold mine tailings. In a batch-mode bioreactor
experiment, this consortium degraded 22 mM SCN-, accumulating ammonium (NH4+) and
sulphate (SO42-) as the major end products. The consortium consisted of a diverse
microbial community comprised of chemolithoautotrophic members, and despite the
absence of an added organic carbon substrate, a significant population of
heterotrophic bacteria. The role of eukaryotes in bioreactor systems is often
poorly understood; however, we found their 18S rRNA genes to be most closely
related to sequences from bacterivorous Amoebozoa. Through combined chemical and
phylogenetic analyses, we were able to infer roles for key microbial consortium
members during SCN- biodegradation. This study provides a basis for understanding
the behaviour of a SCN- degrading bioreactor under autotrophic conditions, an
anticipated approach to remediating SCN- at contemporary gold mines.
PMID- 28510802
TI - Phase I/II study of bi-weekly XELIRI plus bevacizumab treatment in patients with
metastatic colorectal cancer resistant to oxaliplatin-based first-line
chemotherapy.
AB - PURPOSE: We aimed to determine the recommended dose for bi-weekly XELIRI plus
bevacizumab for second-line chemotherapy and examined its safety and efficacy in
patients with metastatic colorectal cancer resistant to oxaliplatin-based first
line chemotherapy. METHODS: Irinotecan and bevacizumab were administered as a
continuous intravenous infusion on Day 1 at 150 mg/mm2 and 5 mg/kg, respectively.
Capecitabine was orally administered in two divided doses on Days 2-8. Each 2
week treatment cycle was defined as a single course of treatment. During Phase I,
we determined the recommended dose for capecitabine. In Phase II trials, efficacy
and treatment safety was verified (UMIN000003934). RESULTS: The recommended dose
of capecitabine was determined to be 2000 mg/m2. Median progression-free survival
was 7.8 months [95% confidence interval (CI) 6.1-10.9 months], and median overall
survival was 18.9 months (95% CI 11.6-28.4 months). Response rate was 17.4% (95%
CI 6.4-28.3%). The most common Grade >=3 hematotoxic adverse events were anemia
(10.9%), neutropenia (10.9%), and leukopenia (8.7%), while the occurrence rate of
Grade >=3 non-hematotoxic adverse events was relatively low (<10%). CONCLUSION:
Bi-weekly XELIRI plus bevacizumab was found to be a safe and effective second
line treatment in patients with metastatic colorectal cancer resistant to
oxaliplatin-based first-line chemotherapy.
PMID- 28510804
TI - Broadening the Lens of System-Based Practice: From Micro to Macro and Basic to
Complex in Residency Training.
AB - OBJECTIVE: This paper aimed to develop a model for understanding the various
dimensions of system-based practice (SBP) and determine the extent to which
psychiatry residents perform behaviors along these dimensions. METHODS: Sixty-one
supervisors from seven psychiatry programs rated resident performance of SBP
behaviors using a 60-item instrument. Multi-dimensional scaling and cluster
analysis were conducted to determine how the instrument items related to one
another and the larger concept of SBP. Average supervisor ratings between
clusters were compared to determine resident performance along the identified SBP
dimensions. RESULTS: The data supports a model of SBP defined along two
dimensions: (1) from micro (patient) to macro (population-based) interventions
and (2) from low to high system complexity. Residents were more likely to perform
behaviors at the patient level compared to those at the population-based level.
CONCLUSIONS: Training in SBP remains predominately focused on the doctor-patient
level and not the greater system of health-care delivery.
PMID- 28510803
TI - Occupational and life-style factors-acquired mutagenicity in agric-workers of
northeastern Brazil.
AB - Pesticides are a complex mixture of chemicals used to protect crops from a number
of pests and diseases. They have been considered as potential mutagenic agents.
This study aims at evaluation of the mutagenic effect of pesticide exposure to
agricultural workers through chromosomal aberrations (CA) and micronucleus (MN)
assay in peripheral blood lymphocytes and oral mucosal cells, respectively. The
exposed group was consisted with 97 farmers, while the control (un-exposed) group
consisted of 55. The results showed a significant (p < 0.05) increase in
frequency of CA and MN in the exposed group. Both CA and MN profiles were linked
to a significant (p < 0.05) co-relation with the confounding factors such as
smoking habits, alcohol, vegetables, tea/coffee, vitamins, and sweetener
consumptions. More cytogenetic events were denoted in smoking and alcohol
consumption as well as non-personal protective equipment (non-PPE) and low/no
vegetables user farmers. In conclusion, a deficiency of dietary and medicaments
derived antioxidants, while consumption of alcohol and tobacco, as well as
effects of radiation, heavy metal poisoning (especially from sweeteners), and non
PPE using habits, may contribute cytogenetic damage to the workers.
PMID- 28510805
TI - Interventional radiology in iatrogenic ureteral leaks: case series and literature
review.
AB - Iatrogenic ureteral injuries are a dramatic complication in medical practice.
Nowadays there are no universal guidelines for their management. The aim of our
study was to evaluate the feasibility of the percutaneous treatment in restoring
ureteral integrity in 19 patients that came to our attention. In each case
retrograde stenting failed and patients were candidates for re-surgery. Our
strategy consists of two phases. The first step is the nephrostomy that allows an
external urinary diversion putting dry the damaged ureteral segment. The second
step is the anterograde ureteral double-J stenting that keeps near the two stumps
promoting the healing of the injured tract. In complete sections, when both
retrograde and anterograde stenting singularly failed, we performed a rendez-vous
technique with a combined radiological trans-nephrostomic access and urological
cystoscopic approach to realign and catheterize the ureteral stumps. In patients
with Bricker urinary diversion, peri-anastomotic leaks were treated by
positioning a multi-hole pig-tail catheter with the inner end in the renal pelvis
and the distal portion outgoing from the cutaneous stoma. Subsequent pyelographic
controls demonstrated the resolution of the ureteral leak in all patients and
none required a surgical re-intervention. Nephrostomies were removed and ureteral
stents were regularly changed. We conclude that interventional uro-radiology may
offer a valid conservative option in iatrogenic urinary injuries.
PMID- 28510806
TI - Role of core needle biopsy in primary breast lymphoma.
AB - Primary breast lymphoma (PBL) may mimic carcinoma clinically and also
mammographic and ecographic distinction is subtle. Despite its rarity, incidence
of PBLs has increased over the last four decades and continues to increase for
younger women and for some subtypes, and for this reason it is increasingly
important to achieve a preoperative pathological diagnosis using core needle
biopsy (CNB) or fine-needle aspiration cytology (FNA). The aim of this
retrospective study was to report our single-center experience in CNBs performed
for histological diagnosis of PBL compared to FNA. From a total of 10,500 CNBs we
found seven patients affected by PBL diagnosed at Careggi Florence University
Hospital, between January 2000 and December 2016. Diffuse large B cell lymphoma
(DLBCL) was the most frequent PBLs and on CNBs specimens was possible do the
fluorescent in situ hybridization analysis to evaluate the presence of
chromosomal translocation. CNB is an effective method for the assessment of PBLs,
especially for DLBCL, in which a correct and fast classification could change the
therapeutic approach and the prognosis.
PMID- 28510807
TI - Incidence of hepatic encephalopathy after transjugular intrahepatic portosystemic
shunt (TIPS) according to its severity and temporal grading classification.
AB - OBJECTIVES: To evaluate hepatic encephalopathy (HE) incidence after transjugular
intrahepatic portosystemic shunt (TIPS) and classify by gravity and frequency.
METHODS: This is a retrospective study of 75 patients with no previous episodes
of HE who underwent TIPS between 2008 and 2014 with clinical follow-up after 6
and 12 months. Patient risk factors evaluated include age, INR (international
normalized ratio), creatinine, bilirubin, and MELD score (Model for End-of-stage
Liver Disease). HE was reported using two classifications: (1) gravity divided in
moderate (West-Haven grades I-II) and severe (III-IV); (2) frequency divided in
episodic and recurrent/persistent. RESULTS: Overall HE incidence was 36% at 6
months, with 12 month incidence significantly decreased to 27% (p = 0.02). 13/75
(17%) patients had one episode of moderate HE, while 3/75 (4%) patients had
severe recurrent/persistent HE. Age was the only pre-TIPS risk predictor. Post
TIPS bilirubin and INR showed variations from basal values only in the presence
of diagnosed HE. Bilirubin significantly increased (p = 0.03) in correlation to
HE severity, whereas INR changes correlated with temporal frequency (p = 0.04).
HE distribution classified for severity is similar at 6 and 12 months, whereas
when classified for frequency shows significant differences (p = 0.04).
CONCLUSIONS: A classification by gravity and frequency attests post-TIPS HE as a
manageable risk. Monitoring of bilirubin and INR may help on clinical management
risk stratification.
PMID- 28510809
TI - Transcatheter arterial embolization for intercostal arterio-esophageal fistula in
esophageal cancer.
AB - BACKGROUND: While esophageal fistula formation in the adjacent organs is
associated with high rates of morbidity and mortality, the management of non
aortic arterio-esophageal fistula has not been frequently reported. CASE
PRESENTATION: A 69-year-old Japanese man who had undergone definitive
chemoradiotherapy for esophageal cancer was admitted to our hospital with
hematemesis. He was diagnosed with mediastinal abscess caused by esophageal
perforation, and esophageal bypass surgery was performed. After 3 days, he
presented with fatal hemoptysis. As angiography revealed an intercostal artery
pseudoaneurysm, transcatheter arterial embolization was performed. CONCLUSIONS:
When patients with esophageal cancer, especially those with a history of
radiotherapy and/or mediastinitis, present with hematemesis and/or hemoptysis,
the possibility of non-aortic arterio-esophageal fistula should be considered.
Transcatheter arterial embolization is an effective treatment for non-aortic
arterio-esophageal fistula.
PMID- 28510808
TI - Development of a contouring guide in three different head set-ups for hippocampal
sparing radiotherapy: a practical approach.
AB - BACKGROUNDS: Irradiation of the hippocampus plays a role in neurocognitive
toxicity. Its delineation is complex and in practice different head position can
vary hippocampus morphology on axial images; so atlas in a single standard
position can result ineffective to describe different hippocampal morphologies in
different head set-up. The purpose of our study was to develop a guide based on
magnetic resonance imaging for hippocampus delineation in three different head
set-ups. MATERIALS AND METHODS: Three patients were selected to elaborate our
guide. Patients were submitted to a planning computed tomography of the brain
district in different head positions: 1 degrees patient in neutral, 2 degrees
patient in over-extended and 3 degrees patient in head hypo-extended position;
axial images of 2-mm thickness were obtained. Computed tomography images were
fused with diagnostic brain magnetic resonance images; then hippocampus was
delineated according to RTOG atlas. Contours were revised by two neuro
radiologists with >5-year expertise in neuroimaging. RESULTS: A guide was
developed for each of three head positions considered. RTOG atlas provided an
easy and reliable guide for hippocampus delineation in neutral position of the
head. Discrepancies were observed in cranial and caudal limit in case of head
over/hypo-extension, as well as in hippocampal morphology near the encephalic
trunk where hippocampus takes an oblong shape in over-extended set-up, and short
and stocky in hypo-extension. CONCLUSION: Our guide can represent a useful tool
for hippocampal delineation in clinical practice and for different anatomic
variations due to different head positions. Certainly, it should be validated in
practice.
PMID- 28510810
TI - Philodendron luisae (Araceae), a new species from Rio de Janeiro State, Brazil.
AB - BACKGROUND: Philodendron is the second largest genus of Araceae, being highly
diverse in the Atlantic Forest biome, with nearly one third of the Brazilian
species occurring in Southern Brazil, particularly in Rio de Janeiro state.
During a local inventory in Silva Jardim municipality, we found a peculiar
population of Philodendron growing in lowland rainforest. RESULTS: After
morphological analysis and comparisons with similar species, the population
proved to be a new undescribed species of subgenus Philodendron section
Macrobelium. CONCLUSIONS: The new species, named Philodendron luisae, is here
described, illustrated and compared to morphologically close species.
PMID- 28510811
TI - Study on the effect of magnetic field treatment of newly isolated Paenibacillus
sp.
AB - BACKGROUND: Symbiotic nitrogen fixation in plants occurs in roots with the help
of some bacteria which help in soil nitrogen fertility management. Isolation of
significant environment friendly bacteria for nitrogen fixation is very important
to enhance yield in plants. RESULTS: In this study effect of different magnetic
field intensity and treatment time was studied on the morphology, physiology and
nitrogen fixing capacity of newly isolated Paenibaccilus sp. from brown soil. The
bacterium was identified by 16S rDNA sequence having highest similarity (99%)
with Paenibacillus sp as revealed by BLAST. Different magnetic intensities such
as 100mT, 300mT and 500mT were applied with processing time of 0, 5, 10, 20 and
30 minutes. Of all these treatment 300mT with processing time of 10 minutes was
found to be most suitable treatment. Results revealed that magnetic treatment
improve the growth rate with shorter generation time leading to increased enzyme
activities (catalase, peroxidase and superoxide dismutase) and nitrogen fixing
efficiencies. High magnetic field intensity (500mT) caused ruptured cell
morphology and decreased enzyme activities which lead to less nitrogen fixation.
CONCLUSION: It is concluded that appropriate magnetic field intensity and
treatment time play a vital role in the growth of soil bacteria which increases
the nitrogen fixing ability which affects the yield of plant. These results were
very helpful in future breading programs to enhance the yield of soybean.
PMID- 28510812
TI - Nostoc sp. extract induces oxidative stress-mediated root cell destruction in
Mimosa pigra L.
AB - BACKGROUND: Mimosa pigra is an invasive weed in some regions of South East Asia
and Australia. Our previous study has revealed that a cyanobacterium, Nostoc sp.,
extract can inhibit root growth in M. pigra seedlings. In this study, some
physiological processes involve oxidative stress-mediated cell death and root
ultrastructure were investigated to clarify the mechanisms of root growth
suppression and bioherbicidal potential of the extract. RESULTS: Nostoc sp.
extract enhanced overproduction of reactive oxygen species (ROS) at 24 h, the
intensity of red fluorescence increased at 72 h, and caused a slightly increased
H2O2 consistent with the activation of scavenging enzymes (catalase, ascorbic
acid peroxidase, glutathione reductase, and peroxidases). This suggests that
oxidative stress occurred in the presence of the extract which was supported by
increased cell death and lipid peroxidation at 24 h. Reduction of malondialdehyde
content and an increase in cell death at 72 h indicated oxidative damage and
cellular leakage. Ultrastructural changes were determined at 72 h by scanning
electron micrographs which confirmed the damage of epidermal and root cap cells
and the disaggregation and destruction of root tip cells. Transmission electron
micrographs showed the dissolution of the middle lamella, deposition of some
substances in vacuoles, and abnormal mitochondria (swollen mitochondria and
indistinct cristae). CONCLUSIONS: Nostoc sp. extract enhance oxidative stress by
ROS production resulting in lipid peroxidation and massive cell death despite the
activation of antioxidative enzymes. Understanding mechanism of action of Nostoc
sp. extract will provide information for application of the extract to use as
natural herbicide for control of M. pigra.
PMID- 28510813
TI - Effects of yam dioscorin interventions on improvements of the metabolic syndrome
in high-fat diet-induced obese rats.
AB - BACKGROUND: The metabolic syndrome (MS) is termed a cluster of multiple metabolic
risk criteria which is positively correlated with cardiovascular disease and type
2 diabetes mellitus (DM). Yam dioscorins have been reported to exhibit biological
activities, however, little is known their preventive effects on the MS.
Therefore, a high-fat (HF) diet was used to induce Wistar rat obesity and then
yam dioscorin (50 mg/kg, dio50) was intervened daily concurrent HF diet (HF diet
+ dio50) for five weeks to check the changes of weights of body and tissues,
blood pressures, and impaired glucose tolerances. The in vitro peptic
hydrolysates of dioscorin with molecular mass between 3 kDa and 10 kDa and less
than 3 kDa were used to determine dipeptidyl peptidase IV (DPP IV) inhibitory
activities which DPP IV inhibitor has been reported to prevent and treat type 2
DM. RESULTS: There were no significant difference in body weights, feed intakes,
feed conversion, and weights of adipose tissues of obese rats in groups of HF and
(HF diet + dio50). However, the systolic blood pressures in obese rats of 2-, 3-
and 4-week dioscorin interventions were showed significantly lower (P < 0.05)
compared to the HF group. The dioscorin intervention (HF+ dio50) was showed
significantly different (P < 0.05) and improved the impaired glucose tolerances
compared to HF group in obese rats by the oral glucose tolerance tests. It was
also found that the fraction with different molecular mass of dioscorin peptic
hydrolysates (5 mg/ml) showed inhibitory activities against DPP IV using
sitagliptin phosphate as positive controls. CONCLUSIONS: Yam dioscorins exhibit
improved MS activities in obese rats which the related mechanisms may need
further investigations.
PMID- 28510814
TI - The endophytic fungi of Salvia miltiorrhiza Bge.f. alba are a potential source of
natural antioxidants.
AB - BACKGROUND: Salvia miltiorrhiza Bge. f. alba is a traditional Chinese herbal drug
with special pharmacological effect on thromboangiitis obliterans. However, the
nature source of S.miltiorrhiza Bge.f.alba is now in short supply because of the
over-collection of the wild plant. To better utilize this resource, the diversity
and antioxidant activity of endophytic fungi isolated from S. miltiorrhiza Bge.
f. alba were investigated. RESULTS: A total of 14 endophytic fungi were isolated
from different parts of S. miltiorrhiza Bge.f.alba. Based on morphological and
molecular identification, the endophytic fungi isolated were classified into four
genera (Alternaria sp., Fusarium sp., Schizophyllum sp. and Trametes sp.). These
fungal extracts were prepared using ethanol and evaluated for their phytochemical
compounds and antioxidant activity. Alternaria alternata SaF-2 and Fusarium
proliferatum SaR-2 are of particular interest because they yielded all of nine
phytochemicals including saponins, phenol, flavonoids, cardiac glycosides,
steroids, tannins, alkaloids, anthroquinone and terpenoids. F. proliferatum SaR-2
and A. alternata SaF-2 also exhibited stronger antioxidant activities by FRAP and
DPPH method, having the higher levels of phenol and flavonoid than those of plant
root. The total amount of phenol and flavonoid quantified were of 21.75, 20.53
gallic acid equivalent per gram and 8.27 and 7.36 MUg/mg of quercetin equivalent
respectively. These two endophytic fungi (SaR-2 and SaF-2) were found to have
comparable scavenging abilities on both FRAP (1682.21 and 1659.05 MUmol/mg,
respectively) and DPPH-free radicals (90.14% and 83.25%, respectively, at 0.1
mg/mL). This is the first report about isolation of endophytic fungi from S.
miltiorrhiza Bge.f.alba and their antioxidant activities. CONCLUSIONS: These
results indicate that the endophytic fungi associated with S. miltiorrhiza Bge.f.
alba can be a potential source of novel natural antioxidants.
PMID- 28510815
TI - Lipid accumulation in response to nitrogen limitation and variation of
temperature in Nannochloropsis salina.
AB - BACKGROUND: This batch study deals with the relation between lipid as well as
triglyceride contents in Nannochloropsis salina and variation in culture
conditions such as nitrogen concentration and temperature. RESULTS: The tested
parameters caused reduction in growth expressed as cell count, optical density
and dry weight, as well strongly involved in lipids and triglycerides
accumulation and significantly affected the lipid productivity. At the beginning
of the work, the concentration of nitrogen in the medium was reduced to three
quarter, half and quarter of the original f2 medium while the temperature kept
constant. After that, the optimal nitrogen concentration (quarter of the original
media) giving high lipid yield was tested with different temperature degrees from
15 to 35 degrees C with five degree intervals. Although the growth was
insignificantly influenced, a considerable increase in lipid and triglyceride
(56.1 and 15.1% of dry weight respectively) was observed when the concentration
of nitrogen in the medium was reduced to the quarter. Moreover, 59.3% lipid and
17.1% triglyceride on the basis of dry weight were obtained by the combination of
25% nitrogen concentration and 30 degrees C. Simple regressions recommended that
the interaction effect of nitrogen limitation and temperature on lipid and
triglyceride accumulation was not as fundamental as for nitrogen limitation
stress. CONCLUSION: The degree of nitrogen availability in the combination of
temperature effect has been identified as the critical determinant for the
maximal production of lipid in N. salina. Nevertheless, major advances in this
field can be considered by studying more stresses techniques and genetic
strategies.
PMID- 28510816
TI - Two new species of Begonia, B. moneta and B. peridoticola (Begoniaceae) from
Sabah, Malaysia.
AB - BACKGROUND: Mount Kinabalu, reknowned for its high biodiversity and endemism, is
a National Park in the State of Sabah on the northern end of the island of
Borneo. Every year many visit the higher part of the Kinabalu National Park,
while most lowland forests in the Park are under-explored. Two unknown species of
Begonia were collected from a peridotic (ultramafic) cliff in the Kinabalu
National Park at ca. 400 m elevation. RESULTS: The two species are named B.
moneta C.-I Peng, Rimi & C. W. Lin and B. peridoticola Rimi, C.-I Peng & C. W.
Lin. Begonia moneta (sect. Baryandra) is similar to B. gueritziana Gibbs, a
widespread species of the same section in Borneo, differing in the peltate (vs.
basifixed) leaves and the smaller flower parts. Also, their chromosome numbers
are different (B. moneta, 2n = 30; B. gueritziana, 2n = 28). The peltate and
succulent foliage of B. moneta is also reminiscent of B. burttii Kiew & S. Julia
and B. payung S. Julia & Kiew, both of sect. Reichenheimia, from Sarawak. Begonia
moneta is distinct from the two species in having branched (vs. entire) placental
lamellae. Additionally, B. moneta differs from B. burttii in having 4 (vs. 5)
tepals in pistillate flowers and markedly unequal (vs. equal) fruit wings.
Begonia moneta differs from B. payung in the smaller leaves and conspicuously
winged (vs. wingless) capsules. Begonia peridoticola (sect. Petermannia)
resembles B. punchak Kiew & S. Julia from limestone areas in Kuching Division,
Sarawak, differing in the entire leaf margin (vs. distantly dentate), much larger
capsular wings (8-11 mm vs. 2-3 mm wide) and yellow, spiral (vs. crimson, U
shaped) styles. CONCLUSION: A careful study of the herbarium materials and
literature supports the recognition of the two new species. Detailed
descriptions, line drawings, color plates, chromsome data, foliar SEM
observations and comparisons with phenetically similar species are provided to
aid in identification.
PMID- 28510818
TI - Six new species of Begonia (Begoniaceae) from limestone areas in Northern
Vietnam.
AB - BACKGROUND: Species of Begonia are richly represented in limestone karst areas
across the Sino-Vietnamese border. More than one hundred species were known, many
of which were documented recently. RESULTS: In continuation of our systematic
studies of Asian Begonia, we report six species of Begonia that are unknown to
science, namely B. caobangensis [sect. Platycentrum], B. circularis, B.
melanobullata, B. langsonensis, B.locii and B. montaniformis [sect. Coelocentrum]
from Northern Vietnam. Diagnostic features that separate them from
morphologically allied species are provided. Somatic chromosome numbers were
determined, which supports their placement in the respective sections. Foliar SEM
microphotographs were taken and described. CONCLUSION: A careful study of the
literature, herbarium specimens and living plants, both in the wild and in
cultivation in the experimental greenhouse, supports the recognition of the six
new species, which are described and illustrated.
PMID- 28510817
TI - Chemical characterization and antioxidative activity of four 3-hydroxyl-3
methylglutaroyl (HMG)-substituted flavonoid glycosides from Graptopetalum
paraguayense E. Walther.
AB - BACKGROUND: Graptopetalum paraguayense E. Walther is a popular traditional
Chinese herb and possesses several health benefits. In earlier studies, we
demonstrated that G. paraguayense showed no genotoxicity and showed several
biological activities. However, the constituents of G. paraguayense have not been
studied yet. In this present study, we isolated and identified the constituents
of the leaves of G. paraguayense E. Walther. RESULTS: A total of seven flavonoid
compounds were isolated from the methanolic extract of G. paraguayense. The four
major compounds isolated were flavonoid glucoside derivatives of quercetin (1, 3)
and kampferol (2, 4), each presenting a 3-hydroxyl-3-methylglutaroyl (HMG)
substituent; compounds 3 and 4-the 2''-acetyl derivatives of 1 and 2,
respectively-are novel compounds isolated from nature for the first time. High
performance liquid chromatography for the quantitative analyses of the four major
HMG-substituted flavonoid glycosides in G. paraguayense E. Walther were
accomplished to acquire the high yields of 1-4 in the methanolic extract (4.8,
5.7, 4.3, and 2.5 mg/g, respectively). Furthermore, the antioxidant activities,
including radical-scavenging, reducing power and lipid peroxidation inhibitory
effects of these isolated flavonoids were also evaluated. All seven of the
isolated flavonoid compounds possessed antioxdative activity. CONCLUSIONS: In
this study of the constituents of the leaves of G. paraguayense E. Walther, we
isolated four major components from its methanolic extract and determined their
structures to be (acetylated) HMG-substituted flavonol glycosides, which are rare
in nature. All seven of the isolated compounds possessed antioxdative activity,
and those flavonoid compounds may be responsible for the functional ingredients
in G. paraguayense. Further investigation of their bioactivities or
pharmacological activities will be continued.
PMID- 28510819
TI - Distyly and floral morphology of Psychotria cephalophora (Rubiaceae) on the
oceanic Lanyu (Orchid) Island, Taiwan.
AB - BACKGROUND: Psychotria cephalophora Merr. (Rubiaceae), a shrub in oceanic islands
of Taiwan and the Philippines, appears to be distylous, but distyly is usually
rare on oceanic islands. To elucidate the functional breeding system of P.
cephalophora can improve our understanding of plant reproductive ecology on
oceanic islands. RESULTS: Field investigations on Lanyu (Orchid Island) off the
coast of southeastern Taiwan revealed the flowers to be distylous with short (S)-
and long (L)-styled morphs, with only one morph per individual. Laboratory
observations revealed that both morphs had stainable pollen grains and indicated
dimorphism in stigmatic papillae and pollen size. In hand pollination
experiments, the pollen tubes reached the base of the style in intermorph
crossing, whereas they rarely penetrated stylar tissue in intramorph crossing and
selfing. Open pollinated S- and L-styled flowers produced fruit. CONCLUSIONS: The
results indicate that the breeding system of P. cephalophora is morphologically
and functionally distylous.
PMID- 28510820
TI - Ficus (Moraceae) and fig wasps (Hymenoptera: Chalcidoidea) in Taiwan.
AB - Although Ficus-associated wasp fauna have been extensively researched in
Australasia, information on these fauna in Taiwan is not well accessible to
scientists worldwide. In this study, we compiled records on the Ficus flora of
Taiwan and its associated wasp fauna. Initial agronomic research reports on Ficus
were published in Japanese in 1917, followed by reports on applied biochemistry,
taxonomy, and phenology in Chinese. On the basis of the phenological knowledge of
15 species of the Ficus flora of Taiwan, recent research has examined the
pollinating and nonpollinating agaonid and chalcid wasps (Hymenoptera:
Chalcidoidea). Updating records according to the current nomenclature revealed
that there are 30 taxa (27 species) of native or naturalized Ficus with an
unusually high proportion of dioecious species (78%). Four species were observed
to exhibit mutualism with more than one pollinating wasp species, and 18 of the
27 Ficus species were reported with nonpollinating wasp species. The number of
nonpollinating wasp species associated with specific Ficus species ranges from
zero (F. pumila) to 24 (F. microcarpa). Approximately half of the Taiwanese fig
tree species have been studied with basic information on phenology and biology
described in peer-reviewed journals or theses. This review provides a solid basis
for future in-depth comparative studies. This summary of knowledge will encourage
and facilitate continuing research on the pollination dynamics of Ficus and the
associated insect fauna in Taiwan.
PMID- 28510821
TI - In vitro culture and production of syringin and rutin in Saussurea involucrata
(Kar. et Kir.) - an endangered medicinal plant.
AB - BACKGROUND: Saussurea involucrata (Kar. et Kir.) commonly known as 'snow lotus'
or 'Xue Lian' is an important plant in the traditional Chinese system of
medicine. The plant contains flavonoids such as syringin and rutin. These
compounds have been reported to be anti-rheumatic, anti-inflammatory and dilate
blood vessels, lower blood pressure, prevent cardiovascular diseases, enhance
immunity, and act as anti-aging, anti-cancer, and anti-fatigue agents. The
species has become endangered due to the excessive collection of S. involucrata
plants in the wild, slower plant growth and ecological destruction of natural
habitats. There is a severe shortage of plant material, while the market demand
is ever increasing. Hence, it is very important to apply tissue culture technique
for plant propagation and production of the bioactive compounds of this species.
RESULTS: Multiple shoot induction and proliferation in shoot base explants
derived from in vitro raised seedlings of S. involucrata was achieved on 3/4
strength of Murashige and Skoog's (MS) basal medium (MSBM) supplemented with 1.0
mg/L-1 BA and 1.5 mg/L-1 NAA. Rooting was induced in 100 % shoots cultured on
1/2X MSBM supplemented with 1.0 mg/L-1 IBA for one week and then transfer to
auxin free medium. The plantlets could be acclimatized successfully by sachet
technique and established in the greenhouse. Maximum callus induction and
proliferation in leaf segments was achieved on 1/2X MSBM supplemented with 0.5
mg/L-1 BA, 0.5 mg/L-1 NAA, 0.4 % gelrite and on incubation at 20 degrees C.
Container closures had an influence on the quality and quantity of callus and
production of the active compounds. The HPLC analysis showed much higher syringin
content in in vitro shoots and callus as compared to commercially available
market crude drug. CONCLUSION: The present study describes an in vitro culture
protocol of Saussurea involucrata. The bioactive compounds, syringin and rutin
could be produced through tissue culture technique without sacrificing the
endangered Saussurea involucrata plants in the wild.
PMID- 28510822
TI - Antibacterial mechanism of the action of Enteromorpha linza L. essential oil
against Escherichia coli and Salmonella Typhimurium.
AB - BACKGROUND: Identification of natural antibacterial agents from various sources
that can act effectively against disease causing foodborne bacteria is one of the
major concerns throughout the world. However, the natural antibacterial agents
identified to date are primarily effective against Gram positive bacteria, but
less effective against Gram negative bacteria. In the present study, Enteromorpha
linza L. essential oil (EEO) was evaluated for antibacterial activity against
Escherichia coli and Salmonella Typhimurium along with the mode of their
antibacterial action. RESULTS: The chemical composition of EEO revealed high
amounts of acids (54.6 %) and alkenes (21.1 %). EEO was effective against both E.
coli and S. Typhimurium. The minimum inhibitory concentration (MIC) and minimum
bactericidal concentration (MBC) values of EEO for both pathogens were 12.5 mg/ml
and 25.0 mg/mL, respectively. EEO at the MIC acted on the loss in viability of E.
coli ATCC 43890, which was used as the model system for evaluation of the
antibacterial mode of action of EEO against Gram negative bacteria. Significant
increase in relative electrical conductivity and K+ concentration were recorded
with respect to time, indicating the disruption of tested E. coli cells owing to
the controlling effect of EEO. Alternation of the morphology of the cell surface,
increase in the release of 260 nm absorbing materials and loss of high salt
tolerance were observed. CONCLUSIONS: The results suggest that EEO induced a
bactericidal effect via structural membrane damage caused by deposition of EEO in
the cytosol or through enzymatic degradation of bacterial intracellular enzymes
that resulted in cellular lysis. Accordingly, EEO can be used as a strong natural
antibacterial agent against Gram negative foodborne pathogens such as E. coli and
S. Typhimurium.
PMID- 28510823
TI - Investigation of metabolites accumulation in medical plant Gentiana rigescens
during different growing stage using LC-MS/MS and FT-IR.
AB - BACKGROUND: Gentiana rigescens, an important medicinal plant in China, has been
widely cultivated in Yunnan province, China. Previous studies were focused on
analysis and determination of the metabolites isolated from this species, the
accumulation of these metabolites during growth period are not yet clear. In this
study, samples for the experiments were obtained by tissue culture. FT-IR and LC
MS/MS method were performed to distinguish the variation on the major metabolites
in G. rigescens during growing stage when combined with chemometrics. RESULTS:
Methodology validations were all within the required limits. The metabolites were
visually different in tissue culture samples and mature plants. The diversity of
metabolites increased proportionally with plant growth. The quantitative analysis
showed the content of gentiopicroside was significantly vary during different
growing stage. The highest content of gentiopicroside (122.93 +/- 7.01 mg/g) was
detected in leaf of regenerated plantlet, whereas its content in root
significantly increased along with underground parts growth. Moreover, flavonoids
mainly distributed in aerial parts showed potential competitive relationship
during plant growth. CONCLUSION: The distribution and accumulation of metabolites
are associated with different parts and plant growth, which provide potential
evidences for the rational application and exploitation of G. rigescens.
PMID- 28510824
TI - Scale-dependent effects of habitat fragmentation on reproduction in the annual
Circaeaster agristis, a narrow endemic and threatened species.
AB - BACKGROUND: Habitat fragmentation and the resulting decline in population size
and density commonly reduce the reproduction of rare and threatened species. We
investigated the impacts of population size and density on reproduction in more
than 30 populations of Circaeaster agristis, a narrow endemic and threatened
species, in 2010 and 2011. We also examined the effects of NND (nearest neighbor
distance) and LNS (local neighbor size), within radii of 0.1 m, 0.2 m and 0.3 m,
on reproduction in two of the populations in 2011. RESULTS: Population size did
not affect fruit (seed) number and fruit set in either year studied. Population
density had an indirect negative effect on fruit number and fruit set as a
consequence of a negative effect on plant size in 2010, but had no effect on
fruit number and fruit set in 2011. Within populations, individual fruit number
did not change, and individual fruit set increased independent of plant size, in
response to increasing NND. Both individual fruit number and individual fruit set
increased, independent of plant size, with increases in LNS within a 0.1 m
radius, but did not change with increases in LNS within radii of between 0.1 m
and 0.2 m radii or between 0.2 m and 0.3 m. CONCLUSIONS: The effect of habitat
fragmentation on reproduction of C. agristis is scale-dependent. In contrast to
the generally accepted idea that fragmentation reduces plant reproduction,
reproductive success may increase in sparse populations or increase in response
to decreases in LNS in C. agristis.
PMID- 28510825
TI - Antimicrobial activity and mechanisms of Salvia sclarea essential oil.
AB - BACKGROUND: Nowadays, essential oils are recognized as safe substances and can be
used as antibacterial additives. Salvia sclarea is one of the most important
aromatic plants cultivated world-wide as a source of essential oils. In addition
to being flavoring foods, Salvia sclarea essential oil can also act as
antimicrobials and preservatives against food spoilage. Understanding more about
the antibacterial performance and possible mechanism of Salvia sclarea essential
oil will be helpful for its application in the future. But so far few related
researches have been reported. RESULTS: In our study, Salvia sclarea oil showed
obvious antibacterial activity against all tested bacterial strains. Minimum
inhibitory concentration (MIC) and minimum bactericide concentration (MBC) of
seven pathogens were 0.05 and 0.1 % respectively. In addition, Salvia sclarea oil
also exhibited a significant inhibitory effect on the growth of Escherichia coli
(E. coli) in phosphate buffer saline (PBS) and meats. After treated with Salvia
sclarea oil, Scanning Electron Microscope (SEM) images can clearly see the damage
of cell membrane; the intracellular ATP concentrations of E. coli and S. aureus
reduced 98.27 and 69.61 % respectively, compared to the control groups; the
nuclear DNA content of E. coli and S. aureus was significantly reduced to 48.32
and 50.77 % respectively. In addition, there was massive leakage of cellular
material when E. coli and S. aureus were exposed to Salvia sclarea oil.
CONCLUSIONS: Salvia sclarea essential oil damaged the cell membrane and changed
the cell membrane permeability, leading to the release of some cytoplasm such as
macromolecular substances, ATP and DNA. In general, the antimicrobial action of
Salvia sclarea essential oil is not only attributable to a unique pathway, but
also involves a series of events both on the cell surface and within the
cytoplasm. Therefore, more experiments need to be done to fully understand the
antimicrobial mechanism of Salvia sclarea essential oil.
PMID- 28510826
TI - Effects of hot-water extracts from Ganoderma lucidum residues and solid-state
fermentation residues on prebiotic and immune-stimulatory activities in vitro and
the powdered residues used as broiler feed additives in vivo.
AB - BACKGROUND: Large amounts of Ganoderma lucidum (GL) commercial products are
provided in the worldwide market such as powders, tea bags, or capsules as
dietary supplements which contained triterpenoids and/or polysaccharides.
Therefore, it was estimated that several thousand tons of GL residues (GLR) are
produced and discarded. For recycling uses, the aim of this study was to evaluate
the benefits of two hot-water extracts from GLR (HWP_GLR) and solid-state
fermentation GLR inoculated with GL mycelia (HWP_GLRF) on the growths of
Lactobacillus rhamnosus and Bifidobacterium longum. The RAW264.7 cells were used
to investigate the effects of HWP_GLR and HWP_GLRF on nitric oxide productions,
phagocytic activities against FITC-labeled E. coli, and to lower
lipopolysaccharide (LPS)-binding capacities. The powders of GLR and GLRF were
used as additives in the commercial feeds for feeding broiler chicks in vivo to
evaluate the immune-stimulatory and prebiotic activities. RESULTS: HWP_GLR and
HWP_GLRF with molecular size 5 to 8 kDa were showed to stimulate growths of L.
rhamnosus and B. longum. It was found that in the presence of polymyxin B HWP_GLR
and HWP_GLRF could stimulate nitric oxide productions, elevate phagocytic
activities against FITC-labeled E. coli, and to lower lipopolysaccharide-binding
capacities in RAW264.7 cells. The broiler chicks were selected for feedings in
vivo. The 1-day-old chicks were fed commercial feeds for 1 week, and then were
fed without or with 4 or 8 % of GLR and GLRF additives for 3 weeks. There was no
significant weight difference among feeding groups. However, the phagocytosis and
natural killer cytotoxicity in the peripheral bloods, and prebiotic activities of
bifidobacteria in feces of GLR and/or GLRF groups were significantly different
compared to the control (P < 0.05). CONCLUSIONS: The GLR, GLRF, and their hot
water extracts with beneficial activities could be processed as feed additives
which could increase the waste-recycling.
PMID- 28510827
TI - Proteomic analysis of broccoli (Brassica oleracea) under high temperature and
waterlogging stresses.
AB - BACKGROUND: The production of broccoli (Brassica oleracea) is largely reduced by
waterlogging and high temperature stresses. Heat-tolerant and heat-susceptible
broccoli cultivars TSS-AVRDC-2 and B-75, respectively, were used for
physiological and proteomic analyses. The objective of this study was to identify
TSS-AVRDC-2 and B-75 proteins differentially regulated at different time periods
in response to waterlogging at 40 degrees C for three days. RESULTS: TSS-AVRDC-2
exhibited significantly higher chlorophyll content, lower stomatal conductance,
and better H2O2 scavenging under stress in comparison to B-75. Two-dimensional
liquid phase fractionation analyses revealed that Rubisco proteins in both
varieties were regulated under stressing treatments, and that TSS-AVRDC-2 had
higher levels of both Rubisco large and small subunit transcripts than B-75 when
subjected to high temperature and/or waterlogging. CONCLUSIONS: This report
utilizes physiological and proteomic approaches to discover changes in the
protein expression profiles of broccoli in response to heat and waterlogging
stresses. Higher levels of Rubisco proteins in TSS-AVRDC-2 could lead to
increased carbon fixation efficiency to provide sufficient energy to enable
stress tolerance under waterlogging at 40 degrees C.
PMID- 28510828
TI - Three new species of Begonia endemic to the Puerto Princesa Subterranean River
National Park, Palawan.
AB - BACKGROUND: Begonia is a mega-diverse genus of flowering plants prone to
generating micro-endemic species, especially on limestone habitats. During
fieldwork in the Puerto Princesa Subterranean River National Park, Palawan
(Philippines), three species were encountered which did not match any previously
described from the region. RESULTS: Following morphological, anatomical,
molecular phylogenetic and cytological investigation a hypothesis of three new
species is supported. The three new species belong to a clade endemic to Palawan
and Borneo. CONCLUSIONS: The limestone habitats in the Puerto Princesa
Subterranean River National Park environs support a unique flora. The description
of three new species from a small area within the park demonstrates how much
remains to be discovered there, and the importance of its continued protection.
PMID- 28510829
TI - Cambial activity and xylogenesis in stems of Cedrus libani A. Rich at different
altitudes.
AB - BACKGROUND: The dynamics of cambial activity and xylogenesis provide information
on how and to what extent wood formation respond to climatic variability. The
Lebanon Cedar (Cedrus libani A.Rich) is a montane tree species which is
distributed along a wide altitudinal range in the northeastern Mediterranean
region, currently considered as a potential forest species for Central Europe
with respect to climate change. This study provides first data on intra-annual
growth dynamics at cellular level using the microcore technique for a montane
Mediterranean tree species at different altitudes within and outside its natural
range. RESULTS: Microcores were collected fortnightly in the growing season of
2013 in order to study temporal dynamics of cambial activity and xylogenesis in
stems of C. libani at different altitudes in the Taurus Mountains (1000 - 2000 m
a.s.l.) and at a plantation at Bayreuth (330 m a.s.l.; Germany). The dormant
cambium consisted of about 5 cells at the Turkish sites and 7 cells at Bayreuth.
Cambial activity set in, when daily minimum temperatures exceeded 0 degrees C
and daily means of air and stem temperature exceeded 5 degrees C. Xylogenesis
started between April and May, ended approximately the end of September to the
beginning of October and lasted 134 (at tree line) to 174 days (at the lowest
Turkish site). Mean ring widths varied from 0.55 to 3.35 mm, with highest values
observed at Bayreuth very likely resulting from a steady water supply during
growing season. Means of daily cell production rates varied from 0.73 to 0.12.
Samples containing traumatic resin ducts occurred only rarely and where not used
for analysis. CONCLUSIONS: In C. libani, onset and dynamics of cambial activity
and xylogenesis are triggered by daily means of stem and air temperatures whereas
water availability has a higher influence on growth rates and cessation of wood
formation. Within sites, duration of xylogenesis does not significantly differ
with respect to age and tree size. C. libani grows well outside its natural range
and thus may be a promising species for forestation in Central Europe with
respect to climate change. We suggest further studies on if/how traumatic resin
ducts influence tree ring width.
PMID- 28510830
TI - Arabidopsis Qc-SNARE genes BET11 and BET12 are required for fertility and pollen
tube elongation.
AB - KEY MESSAGE: BET11 and 12 are required for pollen tube elongation. Pollen tubes
are rapidly growing specialized structures that elongate in a polar manner. They
play a crucial role in the delivery of sperm cells through the stylar tissues of
the flower and into the embryo sac, where the sperm cells are released to fuse
with the egg cell and the central cell to give rise to the embryo and the
endosperm. Polar growth at the pollen tube tip is believed to result from
secretion of materials by membrane trafficking mechanisms. In this study, we
report the functional characterization of Arabidopsis BET11 and BET12, two genes
that may code for Qc-SNAREs (soluble N-ethylmaleimide-sensitive factor attachment
protein receptors). Double mutants (bet11/bet12) in a homozygous/heterozygous
background showed reduced transmission of the mutant alleles, reduced
fertilization of seeds, defective embryo development, reduced pollen tube lengths
and formation of secondary pollen tubes. Both BET11 and BET12 are required for
fertility and development of pollen tubes in Arabidopsis. More experiments are
required to dissect the mechanisms involved.
PMID- 28510832
TI - Chromosome numbers of populations of three varieties of Bidens pilosa in Taiwan.
AB - BACKGROUND: Hairy beggar-ticks (Bidens pilosa L.) is a common invasive plant in
tropical and subtropical regions. The Flora of Taiwan listed three varieties of
B. pilosa in Taiwan, var. minor, var. pilosa and var. radiata. Among the three
varieties, var. radiata was the most recently, in 1970s, introduced into Taiwan.
However, after its introduction into Taiwan, var. radiata has become dominant
over the other two varieties and is considered a serious invasive plant in
lowland of Taiwan. Our previous study showed that var. radiata is self
incompatible and the other two varieties are self-fertile. Could it be possible
that different chromosome numbers contribute to the different breeding systems of
these three varieties? In addition, the heterogeneities of traits of var. radiata
were found higher than those of var. minor and var. pilosa. Is the phenomenon
resulting from the hybridization between var. radiata with other varieties? We
counted chromosome numbers of populations of these three varieties distributed in
Taiwan and conducted hand pollination treatment between var. radiata (as pollen
receiver) and var. minor or var. pilosa (as pollen donor) to provide answer for
the aforementioned questions. RESULTS: No difference was found in chromosome
numbers among populations of the same variety. Forty-eight chromosomes (2n = 48)
were counted for var. radiata while 72 (2n = 72) chromosomes for var. minor and
var. pilosa. Therefore, var. radiata is tetraploid and var. minor and var. pilosa
are hexaploid. No successful hybridization was found between var. radiata and
var. minor or between var. radiata and var. pilosa. CONCLUSIONS: This study
provided the evidence that the invasive plant (B. pilosa var. radiata) has
different chromosome numbers from the other two varieties and is unlikely to
hybridize with the other two varieties.
PMID- 28510831
TI - Distribution of new satellites and simple sequence repeats in annual and
perennial Glycine species.
AB - The repeat sequences occupied more than 50 % of soybean genome. In order to
understand where these repeat sequences distributed in soybean genome and its
related Glycine species, we examined three new repeat sequences-soybean repeat
sequence (SBRS1, SBRS2 and SBRS3), some nonspecific repeat sequences and 45S rDNA
on several Glycine species, including annual and perennial accessions in this
study. In the annual species, G. soja, signals for SBRS1 and ATT repeat can be
found on each chromosome in GG genome, but those for SBRS2 and SBRS3 were located
at three specific loci. In perennial Glycine species, these three SBR repeat
frequently co-localized with 45S rDNA, two major 45S rDNA loci were found in all
tetraploid species. However, an extra minor locus was found in one accession of
the G. pescadrensis (Tab074), but not in another accession (Tab004). We
demonstrate that some repetitive sequences are present in all Glycine species
used in the study, but the abundancy is different in annual or perennial species.
We suggest this study may provide additional information in investigations of the
phylogeny in the Glycine species.
PMID- 28510833
TI - Phenolic constituents and antioxidant properties of five wild species of Physalis
(Solanaceae).
AB - BACKGROUND: Fruits of wild species of the genus Physalis are consumed as food and
calyces and leaves are used in traditional medicine. The phenolic composition of
the species of this genus have been scarcely studied. To contribute to a better
knowledge for the use of all the potential of these wild species of plants,
leaves, fruits, and calyces of five wild species of the genus were analyzed for
their phenolic composition and antioxidant properties. RESULTS: Important tissue-
and species-dependent variations were found. Calyces of Physalis subulata showed
the highest contents of phenolics (176.58 mg of gallic acid equivalents/g dry
tissue), flavonoids (39.63 mg/g dry tissue), and phenolic acids (50.57 mg of
quercitrin equivalents/g dry tissue), and its leaves displayed the highest total
antioxidant capacity (3.59 mg of ascorbic acid equivalents/mL) and one of the
highest reduction powers (0.54 ug of ascorbic acid equivalents/mL). A high
performance liquid chromatography with photodiode array detection analysis
revealed a total of 28 phenolic compounds in foliar tissues (mainly kaempferol-3
O-glycosides), 16 in fruits (mainly phenolic acids), and 16 in calyces (mainly
kaempferol-3-O-glycosides); the profiles of these compounds in the three types of
tissue were species-specific. CONCLUSIONS: The studied species of Physalis are
important sources of phenolics with relevant antioxidant activity. The current
results indicate that phenolic profiles are valuable specific chemical markers
and can be relevant as food tracing and authenticity indicators for plant-based
preparations involving species of Physalis.
PMID- 28510834
TI - The seasonal variations of allelopathic activity and allelopathic substances in
Brachiaria brizantha.
AB - BACKGROUND: Controlling weeds through allelopathy is one strategy to reduce
dependency on synthetic herbicides. The plant shoots of the grass Brachiaria
brizantha incorporated into the field soil were found to inhibit the growth of
several plant species. We investigated the variations of allelopathic activity
and allelopathic substances in B. brizantha harvested in June, October and
January. RESULTS: All extracts of B. brizantha obtained from June, October and
January inhibited the root and shoot growth of cress, lettuce, Phleum pretense
and Lolium multiflorum in a concentration dependent manner. However, the
inhibitory activity of B. brizantha of June and October was greater than that of
B. brizantha of January. Concentrations of three potent allelopathic active
substances, (6R,9S)-3-oxo-alpha-ionol, (6R,9R)-3-oxo-alpha-ionol and 4
ketopinoresinol were also greater in B. brizantha of June and October than those
in B. brizantha of January. CONCLUSION: The results suggest that the allelopathic
activity and the levels of those allelopathic active substances are greater in B.
brizantha of June and October than those in B. brizantha of January. It is
possible that B. brizantha could be useful for a weed suppressive residue or soil
additive materials in the variety of agricultural settings to develop sustainable
agriculture options. The effectiveness of B. brizantha of June and October as a
weed suppressive agent may be greater than that of January.
PMID- 28510835
TI - Plant bioclimatic models in climate change research.
AB - Bioclimatics is an ancient science that was once neglected by many ecologists.
However, as climate changes have attracted increasing attention, scientists have
reevaluated the relevance of bioclimatology and it has thus become essential for
exploring climate changes. Because of the rapidly growing importance of
bioclimatic models in climate change studies, we evaluated factors that influence
plant bioclimatology, constructed and developed bioclimatic models, and assessed
the precautionary effects of the application of the models. The findings obtained
by sequentially reviewing the development history and importance of bioclimatic
models in climate change studies can be used to enhance the knowledge of
bioclimatic models and strengthen their ability to apply them. Consequently,
bioclimatic models can be used as a powerful tool and reference in decision
making responses to future climate changes. The objectives of this study were to
(1) understand how climatic factors affect plants; (2) describe the sources,
construction principles, and development of early plant bioclimatic models
(PBMs); and (3) summarize the recent applications of PBMs in climate change
research.
PMID- 28510837
TI - Range extension of Christisonia scortechinii from mainland Southeast Asia into
Borneo, and notes on the distinction between Aeginetia and Christisonia
(Orobanchaceae).
AB - BACKGROUND: Christisonia is a little-documented and poorly studied root-parasitic
genus in the Orobanchaceae occurring in India, China, Indochina and part of the
Malesian region. Recent collection of a Christisonia taxon in Kinabalu Park in
Sabah, Borneo, taxonomically identical to earlier Sabah collections that have
hitherto not been recorded in the literature, led to an assessment of the
taxonomic identity of the species against Christisonia scortechinii, C.
siamensis, C. sinensis and related species. RESULTS: Some taxa in China,
Indochina, the Malay Peninsula, and the Philippines are morphologically identical
to the Borneo taxon except in the number of calyx lobes, but differ by several
distinctive characters from other well-distinguished species in the region.
Studies of dried herbarium specimens, augmented by photographic images of
different stages of fresh flowering material and a scrutiny of available
descriptions confirmed that the calyx has two primary lobes in the bud that may
separate into 3-5 portions, giving a variable number of apparent lobes in
specimen material collected at different localities. This new scrutiny of the
calyx also permitted an improved description of the calyx differences that
separate Christisonia and the closely related Aeginetia, which have not been
clearly elucidated in the past. CONCLUSIONS: Christisonia scortechinii Prain
(Orobanchaceae), the only species that was described as having an initially
spathaceous calyx among species of this root-parasitic genus, is newly recorded
for Borneo (including Kinabalu Park, where its presence has been overlooked). The
range of the species in mainland Southeast Asia, previously extended from
Peninsular Malaysia to Thailand and Vietnam, is here further extended to Laos and
China. Christisonia wightii Elmer (relevant to the Philippines) and C. sinensis
Beck (China) are reduced to synonymy.
PMID- 28510836
TI - Great fraction of dissolved organic C and N in the primary per-humid
Chamaecyparis forest soil.
AB - BACKGROUND: Labile organic matter plays a crucial role in a variety of forest
functions, however, our understanding to its quality and quantity across various
forests is limited, particularly primary forests. We investigated soil labile C
and N (i.e. microbial biomass C and N, dissolved organic carbon (DOC) and
nitrogen (DON), associated ammonium, and nitrate) at three topographic locations
(i.e. summit, footslope and lakeshore) in a primary Chamaecyparis forest of
Taiwan. The following hypotheses are tested in this study: (1) This undisturbed
Chamaecyparis forest shows the great size of soil labile C and N; (2) there is an
evident topographic effect on the distribution of soil labile C and N and the
associated inorganic N over seasons. RESULTS: Fulfilling with our first
hypothesis, the considerable size of labile C and N in this forest soil was
quantified. Abundant C availability and the acidity of soils in this forest
favoured ammonium production over nitrate. The undisturbed environment with per
humid and acidic soil was linked to the high concentrations of soil DOC and DON
as the dominant form in N dynamics. In contrast to our second hypothesis,
topographic effects on soil labile C and N were generally not evident, suggesting
the homogeneous soil environment across various topographic locations in this
Chamaecyparis forest. CONCLUSIONS: This study illustrates the sustainable
importance of primary montane forests for being sources of DOC and DON.
PMID- 28510838
TI - Impatiens pandurata (Balsaminaceae), a new species from Yunnan, China.
AB - BACKGROUND: The species-rich genus Impatiens is mainly distributed throughout
much of tropical Africa, India, southwest Asia, southern China and Japan. There
are more than 270 species recorded in China, most of which are restricted to the
southwest. An unknown species of Impatiens was collected from Yunnan, southwest
China. RESULTS: Impatiens pandurata Y. H. Tan & S. X. Yu, a new species of
Balsaminaceae from Jinping County and Malipo County, Yunnan, China is similar to
I. apalophylla and I. clavigera in having racemose inflorescences, 4 lateral
sepals, hammer-shaped capsules and ellipsoid seeds, but differs in having leaves
with oblanceolate blades aggregated at the top of the stem, 3-5-flowered racemes,
a yellow lower sepal without reddish patches, yellowish flowers, and a dorsal
petal with stalks at the base. Molecular phylogenetic analyses of sequences from
both nuclear ribosomal and plastid genes confirm that this new species is
distinct from morphologically similar species previously recorded. CONCLUSION:
With the support of careful morphological studies and phylogenetic analysis, I.
pandurata is a species new to science.
PMID- 28510839
TI - Two rare ophiocordycipitaceous fungi newly recorded in Taiwan.
AB - BACKGROUND: Ophiocordycipitaceae is a highly diverse fungal family parasitizing a
wide range of arthropods and hypogeous fungi. We collected two
ophiocordycipitaceous species previously unknown in Taiwan: one emerged from
hypogeous fruiting bodies of an Elaphomyces fungus and the other was associated
with dragonflies. RESULTS: Based on gross morphology, microscopic features, ITS
sequences, and hosts, the two ophiocordycipitaceous fungi were identified as
Tolypocladium japonicum and Ophiocordyceps odonatae. We isolated axenic cultures
of these two fungi, and their anamorphs were obtained. The simplicillium-like
anamorph of T. japonicum is described herein for the first time. The anamorph of
O. odonatae produce conidia holoblastically in sympodial sequence and is
assignable to Hymenostilbe. A dichotomous key to the species of
Ophiocordycipitaceae reported in Taiwan is provided. CONCLUSION: A thorough
literature study indicates that the two fungi reported herein have rarely been
collected. Our identifications of T. japonicum and O. odonatae agree well with
descriptions in the literature and are highly supported by DNA sequence analysis.
PMID- 28510840
TI - Two conserved oligosaccharyltransferase catalytic subunits required for N
glycosylation exist in Spartina alterniflora.
AB - BACKGROUND: Asparagine (N)-linked glycosylation is one of the most crucial post
translational modifications, which is catalyzed in the lumen of the endoplasmic
reticulum (ER) by the oligosaccharyltransferase (OST) in eukaryotic cells.
Biochemical and genetic assay leads to the identification of the nine subunits
(Ost 1-6, Stt3, Swp1 and Wbp1) of the yeast OST and in which Stt3p is proposed
playing a central and conserved role in N-glycosylation. Two STT3 isoform genes,
STT3A and STT3B, exist in the plant and mammal genomes. OST with different
catalytic STT3 isoforms has different enzymatic properties in mammals. The
mutation of STT3A in Arabidopsis thaliana causes a salt hypersensitive phenotype
the inhibited root growth and swollen root tips suggesting protein N
glycosylation is indispensable for plant growth and development. Spartina
alterniflora is widely used for shoreline protection and tidal marsh restoration
due to the strong salt tolerance although the exact molecular mechanism is little
known. To explore the possible biological roles of N-glycosylation in plant
adaptive resistance to salinity stress, we cloned the STT3 genes from S.
alterniflora and heterogenously expressed them in Arabidopsis mutant to observe
the functional conservation. RESULTS: SaSTT3A and SaSTT3B genes were cloned from
Spartina alterniflora. SaSTT3A genomic sequences spanned over 23 exons and 22
introns, while SaSTT3B had 6 exons and 5 introns. The gene structures of both
genes were conserved among the analyzed plant species. Subcellular localization
and transmembrane structure prediction revealed that these two genes had 13 and
11 transmembrane helices respectively. The functional complementation in which
the cDNA of SaSTT3A and SaSTT3B driven by CaMV 35S promoter completely or
partially rescued Arabidopsis stt3a-2 mutant salt-sensitive phenotype, indicating
STT3A functions conservatively between glycophyte and halophyte and N
glycosylation might be involved in plant resistance to salinity. CONCLUSIONS: Two
STT3 isoform genes, SaSTT3A and SaSTT3B, were cloned from S. alterniflora and
they were evolutionally conserved at gene structure and coding sequences compared
with their counterparts. Moreover, SaSTT3 genes could successfully rescue
Arabidopsis stt3a-2 salt-sensitive phenotype, suggesting there exists a similar N
glycosylation process in S. alterniflora. Here we provided a first piece of
evidence that the N-glycosylation might be involved in salt tolerance of
halophyte.
PMID- 28510841
TI - Sexual specialization in phenology in dioecious Ficus benguetensis and its
consequences for the mutualism.
AB - BACKGROUND: Timing of reproductive events has become central in ecological
studies linking success in pollination and seed dispersion to optimizing the
probability and periods of encounters with pollinators or dispersers. Obligate
plant-insect interactions, especially Ficus-fig wasp mutualisms, offer striking
examples of fine-tuned encounter optimization as biological cycles between
mutualistic partners are deeply dependent on each other and intertwined over
generations. Despite fig flowering phenology being crucial in maintaining Ficus
fig wasp mutualisms, until now, the forces of selection shaping the phenological
evolution of dioecious fig trees have received little attention. By conducting a
2-year survey of a population of Ficus benguetensis in Northern Taiwan, we
assessed whether environmental factors or other selective pressures shape the
phenology of male and female fig trees. RESULTS: Constraints by mutualistic
pollinating wasps and seed dispersers, rather than climatic factors, appeared to
mainly shape fig phenology and allometry in F. benguetensis. We identified a new
sexual specialization in dioecious fig trees: the position of fig production. We
propose that the continuous male fig production on tree trunks can enhance the
survival of pollinating fig wasps through faster localization of receptive figs
while reducing the mutualistic conflict between the fig and its obligate
pollinators. By contrast, in female trees, fig production is massive in summer,
located on the twigs of the foliar crown and seem more related to seed dispersal
and germination. CONCLUSIONS: Identifying variations in the allometry and
phenology of dioecious figs provide valuable insights into how monoecious and
dioecious species resolve mutualism conflicts and into the emergence of dioecy in
fig trees.
PMID- 28510842
TI - Arabidopsis SFAR4 is a novel GDSL-type esterase involved in fatty acid
degradation and glucose tolerance.
AB - BACKGROUND: SFARs (seed fatty acid reducers) belonging to the GDSL
lipases/esterases family have been reported to reduce fatty acid storage and
composition in mature Arabidopsis seeds. GDSL lipases/esterases are hydrolytic
enzymes that possess multifunctional properties, such as broad substrate
specificity, regiospecificity, and stereoselectivity. Studies on the
physiological functions and biochemical characteristics of GDSL lipases/esterases
in plants are limited, so it is important to elucidate the molecular functions of
GDSL-type genes. RESULTS: We found that SFAR4 (At3g48460), a fatty acid reducer
belonging to the Arabidopsis GDSL lipases/esterases family, was intensely
expressed in embryo protrusion, early seedlings, and pollen. The characterization
of recombinant SFAR4 protein indicated that it has short-length p-nitrophenyl
esterase activity. In addition, SFAR4 enhanced the expression of genes involved
in fatty acid metabolism during seed germination and seedling development. SFAR4
elevated the expression of COMATOSE, which transports fatty acids into
peroxisomes, and of LACS6 and LACS7, which deliver long-chain acetyl-CoA for beta
oxidation. Furthermore, SFAR4 increased the transcription of PED1 and PNC1, which
function in importing peroxisomal ATP required for fatty acid degradation. SFAR4
has another function on tolerance to high glucose concentrations but had no
significant effects on the expression of the glucose sensor HXK1. CONCLUSIONS:
The results demonstrated that SFAR4 is a GDSL-type esterase involved in fatty
acid metabolism during post-germination and seedling development in Arabidopsis.
We suggested that SFAR4 plays an important role in fatty acid degradation, thus
reducing the fatty acid content.
PMID- 28510843
TI - Three new species of Primulina (Gesneriaceae) from limestone karsts of China
based on morphological and molecular evidence.
AB - BACKGROUND: With more than 160 described species, Primulina is one of the most
characteristic plant groups of the Sino-Vietnamese limestone flora. In our
continous botanical inventory of the limestone flora of South China, we collected
three new Primulina species not identifiable to known species. RESULTS: Molecular
phylogenetic analyses based on nuclear ITS and chloroplast trnL-F and trnH-psbA
sequences strongly support the placement the three new species in Primulina. In
addition to morphological differences, DNA sequences of all these three new
species show substantial divergencies, sustaining the recognition of these three
new species. CONCLUSIONS: Based on morphological and molecular data, we describe
and illustrate three new Primulina species: P. maculata, P. pengii, and P.
yangshanensis.
PMID- 28510844
TI - Influence of alpha-terpineol on the growth and morphogenesis of Penicillium
digitatum.
AB - BACKGROUND: Plant essential oils could act effectively against postharvest
diseases, alpha-terpineol, a typical terpenoid of plant essential oils, exhibited
strong antifungal activity in against Penicillium italicum, but the possible
action mechanism remains undetermined. In present study, alpha-terpineol was
evaluated for antibacterial activity against Penicillium digitatum along with the
mode of their antibacterial action. RESULTS: The results showed that mycelial
growth of P. digitatum was strongly inhibited by alpha-terpineol, with the
minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC)
of 2.00 and 8.00 ul/ml, respectively. Scanning electron microscopy observation
revealed that alpha-terpineol obviously altered the morphology of P. digitatum
hyphae by causing the loss of cytoplasm and distortion of mycelia. A rapid
increase in the membrane permeability of P. digitatum was observed after treated
with MIC or MFC of alpha-terpineol, evidenced by the release of cell
constituents, the extracellular conductivity, and the extracellular pH. In
addition, alpha-terpineol apparently induced a decrease in total lipid contents
of P. digitatum cells, indicating the destruction of cell membrane structures
after treatment. CONCLUSIONS: Based on our study, alpha-terpineol might affect
the cell wall synthesis and lead to the disruption of cell wall. The cell wall
disruption affected fungal morphogenesis, the integrity of membrane and leakage
of intracellular components, these results suggested that alpha-terpineol
treatment inhibited the growth of P. digitatum.
PMID- 28510845
TI - Effect of potassium deficiency on antioxidant status and cadmium toxicity in rice
seedlings.
AB - BACKGROUND: Cadmium (Cd) is one of the most toxic heavy metals and inhibits
physiological processes of plants. Potassium (K) is an essential macronutrient in
plants. K deficiency and Cd stress represent two different abiotic stress
conditions that occur in the field simultaneously. In this study, effects of K
deficiency on antioxidant status and Cd toxicity in rice seedlings were
investigated. RESULTS: K deficiency significantly decreased K concentration in
shoots and roots. However, fresh weight and dry weight of rice seedlings were not
affected by K deficiency. The activities of antioxidant enzymes (superoxide
dismutase, ascorbate peroxidase, glutathione reductase, and catalase) in K
deficient leaves were higher than respective control leaves. However, K
deficiency had no effect on the content of antioxidants (ascorbate and
glutathione). Cd toxicity was judged by the decrease in biomass production,
chlorosis, and induction of oxidative stress. Based on these criteria, we
demonstrated that K deficiency protected rice seedling from Cd stress. Moreover,
chlorophyll concentration was higher in K-deficient shoots and roots than their
respective control shoots and roots. CONCLUSIONS: Our results indicated that K
deficiency protects rice seedlings from Cd toxicity. This protective effect of K
deficiency is mainly due to enhanced antioxidant enzyme activities but not
inhibition of Cd uptake.
PMID- 28510846
TI - Reproductive phenology and pre-dispersal fruit predation in Atriplex halimus L.
(Chenopodiaceae).
AB - BACKGROUND: The flowering phenology pattern of Atriplex halimus was studied in a
Mediterranean habitat in order to analyze protandry effectiveness. Fruit set
evolution was recorded over two years and the impact of pre-dispersal predation
by insects was also evaluated. RESULTS: The flowering phenology coincided in 2006
and 2007, starting in mid-July and reaching full flowering at the end of August
in both years. Inflorescences are composed of glomerules with 8.78 +/- 2.79 male
flowers and 4.57 +/- 2.58 female flowers, with no significant differences in
position on the inflorescence. The peaks of male and female flower anthesis were
reached in mid-August, but the male maximum occurred one week before the female.
Plants at the start of flowering only bear male flowers, but female flowers soon
appear. Fruit set starts at the end of August; all the flowers were transformed
into fruit by mid-September and their development continued to the beginning of
October, when fruit structures had matured and began to drop. Fruit predation
started at the end of September and reached maximum intensity in mid-October.
CONCLUSIONS: At population level, male and female flowers seemed to open in the
same weeks, but at plant and glomerule level male flowers opened one week before
the females. Fruit predation levels were 62.42 and 43.14% in 2006 and 2007
respectively, with no significant differences between different parts of the
inflorescence. And larvae of Coleophoridae were the most abundant predators.
PMID- 28510847
TI - Characterization of the decline and recovery of heat-treated Scenedesmus
vacuolatus.
AB - BACKGROUND: To find out how algal cells cope with and recover from heat stress,
the small vegetative cells of the synchronous Scenedesmus vacuolatus culture were
subjected to a heat pretreatment (46.5 degrees C for 1 h) followed by dark
recultivation. The changes in physiological activities and morphology of
Scenedesmus cells were continuously monitored throughout the course of decline
and recovery. RESULTS: It was found that the heat treatment, though completely
inhibited photosynthesis, did not kill Scenedesmus cells. These cells, during
dark recultivation, could make a fast repair and regained the ability of
proliferation. We suggest that they entered a 'stand-by' state, which was
characterized by condensed chromatin, partially functional but morphologically
altered chloroplasts, disappeared vacuoles, slightly shrunk protoplast and intact
plasma membranes. These stressed cells, on the surface, seemingly were undergoing
some kind of disintegration, could readily and quickly return to normal cells
upon illumination. Cell death occurred only after a long period of darkness (>48
h). CONCLUSIONS: Our results suggest that the recovery of algal cells from stress
damage may actually proceed in two steps. The middle "stand-by' stage normally is
gone through too rapidly to be detected unless cells are kept in the dark.
PMID- 28510848
TI - Cytokinin, auxin, and abscisic acid affects sucrose metabolism conduce to de novo
shoot organogenesis in rice (Oryza sativa L.) callus.
AB - BACKGROUND: Shoot regeneration frequency in rice callus is still low and highly
diverse among rice cultivars. This study aimed to investigate the association of
plant hormone signaling and sucrose uptake and metabolism in rice during callus
induction and early shoot organogenesis. The immatured seeds of two rice
cultivars, Ai-Nan-Tsao 39 (ANT39) and Tainan 11 (TN11) are used in this study.
RESULTS: Callus formation is earlier, callus fresh weight is higher, but water
content is significant lower in ANT39 than in TN11 while their explants are
inoculated on callus induction medium (CIM). Besides, the regeneration frequency
is prominently higher in ANT39 (~80%) compared to TN11 callus (0%). Levels of
glucose, sucrose, and starch are all significant higher in ANT39 than in TN11
either at callus induction or early shoot organogenesis stage. Moreover, high
expression levels of Cell wall-bound invertase 1, Sucrose transporter 1 (OsSUT1)
and OsSUT2 are detected in ANT39 at the fourth-day in CIM but it cannot be
detected in TN11 until the tenth-day. It suggested that ANT39 has higher callus
growth rate and shoot regeneration ability may cause from higher activity of
sucrose uptake and metabolism. As well, the expression levels of ORYZA SATIVA
RESPONSE REGULATOR 1 (ORR1), PIN-formed 1 and Late embryogenesis-abundant 1,
representing endogenous cytokinin, auxin and ABA signals, respectively, were also
up-regulated in highly regenerable callus, ANT39, but only ORR1 was greatly
enhanced in TN11 at the tenth-day in CIM. CONCLUSION: Thus, phytohormone signals
may affect sucrose metabolism to trigger callus initiation and further de novo
shoot regeneration in rice culture.
PMID- 28510849
TI - Inhibitory activities of acteoside, isoacteoside, and its structural constituents
against protein glycation in vitro.
AB - BACKGROUND: Advanced glycation end products (AGE) are substances that can induce
insulin resistance in adipocyte, hepatocyte and muscle cells. This resistance
correlates highly with cardiovascular disease and diabetic complications.
Acteoside (A), a phenylethanoid glycoside, is an active compound in several
plants and traditional herbal medicines. Acteoside, its structural isomer,
isoacteoside (I), and their constituents, caffeic acid (C) and 3,4
dihydroxyphenylethanol (D), were used in the study to investigate the inhibitory
activity against AGE formations in vitro. RESULTS: AGE formations were detected
by anti-(Nepsilon-(carboxymethyl)lysine (anti-CML), using bovine serum albumin
(BSA)/glucose (glc) and BSA/galactose (gal) as models, or by anti-argpyrimidine
(anti-AP), using BSA/methylglyoxal (MGO) as models. It was found that A, I, C, or
D, each at 5 mM, could attenuate the CML formations detected by ELISA in the
BSA/gal model of a 3-day or 5-day reaction, and showed significant differences (P
< 0.01 or P < 0.001) compared to the control. However, these compounds showed a
minor effect after a 7-day incubation. It was also found that C or D could lower
the CML formations in the BSA/glc model and showed significant differences (P <
0.05 or P < 0.01) compared to the control after a 3-day, 5-day and 7-day
reaction. It was found that A, I, C, or D, each at 0.5 mM or 5 mM, could
attenuate the AP formations in the BSA/MGO model of a 3-day reaction and showed
significant differences (P < 0.001) compared to the control. CONCLUSIONS: The
results suggest the potential anti-glycation activities of A and I in vitro may
apply to cell models at higher glucose concentrations or to diabetic animal
models, and need further investigation.
PMID- 28510850
TI - Chemical composition and tyrosinase inhibitory activity of Cinnamomum cassia
essential oil.
AB - BACKGROUND: Essential oils extracted from aromatic plants exhibit important
biological activities and have become increasingly important for scientific
research. The essential oil extracted from Cinnamomum cassia Presl (CC-EO) has
various functional properties, however, little information is available regarding
the tyrosinase inhibitory activity. Therefore, the objectives of this study were
to investigate the chemical composition and tyrosinase inhibitory activity of the
CC-EO. RESULTS: cis-2-methoxycinnamic acid (43.06%) and cinnamaldehyde (42.37%)
were found to be the two major components of the CC-EO identified by gas
chromatography-mass spectrometry (GC-MS). The inhibitory activities of CC-EO and
its major constituents were further evaluated against mushroom tyrosinase. The
results showed that CC-EO and cinnamaldehyde exhibited anti-tyrosinase activities
with IC50 values of 6.16 +/- 0.04 mg/mL and 4.04 +/- 0.08 mg/mL, respectively.
However, cis-2-methoxycinnamic acid did not show any anti-tyrosinase activity.
The inhibition kinetics were analyzed by Lineweaver-Burk plots and second
replots, which revealed that CC-EO and cinnamaldehyde were mixed-type inhibitors.
The inhibition constants (Ki) for CC-EO and cinnamaldehyde were calculated to be
4.71 +/- 0.09 mg/mL and 2.38 +/- 0.09 mg/mL, respectively. CONCLUSION: These
results demonstrate that CC-EO and its major component, cinnamaldehyde, possess
potent anti-tyrosinase activities and may be a good source for skin-whitening
agents.
PMID- 28510851
TI - 24-epibrassinolide restores nitrogen metabolism of pigeon pea under saline
stress.
AB - BACKGROUND: Several studies have shown that brassinosteroids attenuate the
effects of salt stress. However, nothing is known about their effects on amino
acid transport, nor the effects of these hormones on nitrate uptake under saline
conditions. This study set out to determine the effects of 24-epibrassinolide, at
concentrations of 10-7 M and 0.5 * 10-9 M, and clotrimazole (inhibitor of
brassinosteroid synthesis), at 10-4 M, on nitrate uptake and metabolism in plants
of C. cajan (L.) Millsp, cultivar C11, growing under salinity. The following
aspects were analyzed: levels of proteins, amino acids, nitrate, nitrate
reductase of roots and the composition of xylem sap amino acids. RESULTS:
Salinity reduced the proportion of N-transport amino acids ASN (the major
component), GLU, ASP and GLN. The effect of the hormone in reducing the adverse
effects of salt was related to the reestablishment (totally or partially) of the
proportions of GLU, ASN and GLN, transported in the xylem and to the small but
significant increase in uptake of nitrate. Increased nitrate uptake, induced by
24- epibrassinolide, was associated with a higher activity of nitrate reductase
together with greater levels of free amino acids and soluble proteins in roots of
plants cultivated under saline conditions. CONCLUSION: The decline in several
components of nitrogen metabolism, induced by salt, was attenuated by 24
epibrassinolide application and accentuated by clotrimazole, indicating the
importance of brassinosteroid synthesis for plants growing under salinity.
PMID- 28510852
TI - Synotis baoshanensis (Asteraceae), a new species from Yunnan, China.
AB - BACKGROUND: Synotis (Asteraceae; Senecioneae) is a genus of about 55 species
mostly distributed in the Sino-Himalayan region. During a botanical expedition in
southwestern China in 2012, we found an unusual population of Synotis in
southwestern Yunnan Province. To determine the taxonomic identity of the
population, we carried out gross-morphological, floral micromorphological, and
cytological observations. RESULTS: Our gross-morphological observations have
shown that the population is most similar to Synotis auriculata C. Jeffrey & Y.
L. Chen in leaf shape and in the number of phyllaries and florets, but readily
distinguishable by the glabrous stem and petiole (vs. glandular pubescent), the
exauriculate petiole (vs. auriculate), the uppermost leaves obviously smaller
than the middle ones (vs. almost equally sized), and the larger ray florets (4
4.5 mm vs. ca. 2.5 mm). The floral micromorphological observations on the
population agree with previous reports for other species of Synotis. The
chromosomes of the population are counted to be 2n = 40. Its karyotype is
formulated as 2n = 20m + 14sm + 6st. CONCLUSIONS: The population was determined
to represent a new species, i.e. Synotis baoshanensis M. Tang & Q. E. Yang, which
is described herein. The species belongs to Synotis ser. Microglossae.
PMID- 28510853
TI - Leucaena leucocephala leachate compromised membrane integrity, respiration and
antioxidative defence of water hyacinth leaf tissues.
AB - BACKGROUND: Water hyacinth is an invasive aquatic weed in many regions of the
world. In this study, the bioherbicidal potential of allelopathic plant Leucaena
leucocephala against water hyacinth was investigated using a leaf disc assay.
RESULTS: L. leucocephala leachate enhanced electrolyte leakage from water
hyacinth leaf discs in a concentration-dependent manner. Control experiments
eliminated the possibilities that increased membrane permeability in the leachate
treated leaf discs was due to pH or osmotic effects of the leachate. Thus, the
loss of membrane stability in the leachate-treated leaf discs was likely due to
phytotoxins detected in the leachate, namely mimosine and phenolic constituents.
Decline in tissue respiration was detected in leachate-treated water hyacinth
leaf discs. This suggests that the L. leucocephala leachate may contain compounds
which acted as respiratory inhibitors. Enhanced reactive oxygen species
production coincided with inhibition of catalase and ascorbate peroxidase
activities in the leachate-treated water hyacinth leaf tissues. The injurious
effects of L. leucocephala leachate on water hyacinth leaf discs probably
involved direct inhibition of antioxidant enzymes in addition to direct
involvement of some allelochemicals in reactive oxygen species formation.
CONCLUSION: In summary, the toxic effects of L. leucocephala leachate on water
hyacinth leaf discs likely lay in its ability to effectively compromise the
membrane integrity, tissue respiration and antioxidant defence of the latter.
PMID- 28510854
TI - Dehydroascorbate reductase and monodehydroascorbate reductase activities of two
metallothionein-like proteins from sweet potato (Ipomoea batatas [L.] Lam.
'Tainong 57') storage roots.
AB - BACKGROUND: Metallothionein (MT) is a group of proteins with low molecular masses
and high cysteine contents, and it is classified into different types, which
generally contains two domains with typical amino acid sequences. RESULTS: In
this report, two full-length cDNAs (MT-1 and MT-II) encoding MT-like proteins
were isolated from the roots of sweet potato (Ipomoea batatas [L.] Lam. 'Tainong
57'). Their open reading frames contained 642 and 519 nucleotides (66 and 81
amino acids) for MT-1 and MT-II, respectively, and exhibited a relatively low
amino acid sequence similarity. On the basis of the amino acid sequence
similarity and conserved residues, it is suggested that MT-I is a member of the
plant MT Type-I family, and MT-II is a member of the plant MT Type-II family. The
corresponding mRNA levels of MT-1 and MT-II were the highest found in the storage
roots. Recombinant MT-1 and MT-II protein overproduced in E. coli (M15) was
purified by Ni2+-chelated affinity chromatography. MT-1 and MT-II reduced
dehydroascorbate (DHA) in the presence of glutathione (GSH) to regenerate L
ascorbic acid (AsA). However, without GSH, MT-1 and MT-II has very low DHA
reductase activity. And AsA was oxidized by AsA oxidase to generate
monodehydroascorbate (MDA) free radical. MDA was also reduced by MT-1 and MT-II
to AsA in the presence of NADH mimicking the MDA reductase catalyzed reaction.
CONCLUSIONS: These data suggest that MT-1 and MT-II have both DHA reductase and
MDA reductase activities. MT-1 and MT-II are apparently the first reported plant
MTs exhibiting both DHA and MDA activities in vitro.
PMID- 28510855
TI - Phenology and pollinating wasp dynamics of Ficus microcarpa L.f.: adaptation to
seasonality.
AB - BACKGROUND: In the obligate plant/pollinator mutualism, pollinator abundance is
conditioned by the host resource. In order to investigate the population
fluctuation of pollinating wasps and the phenological processes involved, this
study examined the dual dynamics of the pollinator and the syconium phenology of
a seasonal fruited fig tree population, Ficus microparpa, in Taipei, Taiwan.
RESULTS: Our results revealed three seasons in the annual phenology: spring crop,
summer-fall crop and winter trough seasons. The syconium quantity was correlated
most significantly with temperature based on the generalized linear model with
the meteorological data transformed by a principal component analysis. The
pollinator population showed an increasing trend in spring, reached the maximum
abundance in summer, and then declined drastically in winter, consistent with the
syconium production fluctuation. With the small amount of local pollinators from
the winter syconia and potential immigrating foundresses from other populations,
the pollinator population size can increase very quickly from almost zero to over
40,000 wasps for this 29-tree local population within a season. CONCLUSION: This
syconium phenological scheme, coupled with the fast-recovery rate of pollinators,
may explain the worldwide adaptation and invasion of Ficus microcarpa.
PMID- 28510856
TI - Morphological and molecular characteristics of Homoeostrichus formosana sp. nov.
(Dictyotaceae, Phaeophyceae) from Taiwan.
AB - BACKGROUND: In the marine brown macroalgae, the morphological characters are
highly similar between two widely distributed genera, Homoeostrichus and Zonaria
(Dictyotaceae), thereby resulting in the difficulty of exploring their hidden
biodiversity. Owing to the help of the molecular tools, it is now easy for
scientists to objectively describe a new species in nature. In this study, we
make a description on the Homoeostrichus formosana sp. nov. from Taiwan, Indo
Pacific Ocean based on the morphological evidence and molecular data. RESULTS:
Our morphological observations revealed that this species has marginal row of
apical cells responsible for thallus growth and the thallus with four layers of
cells except the marginal regions. The cortical cell lies upon each medullary
cell in transverse section, and two cortical cells upon each medullary cell in
longitudinal section. Tetrasporangium is developed from cortical cell with stalk
cell and singly scattered over the thallus surface, and has no indusia and
paraphyses. Molecularly, the phylogenetic trees based on SSU, psaA, psbA, and
rbcL gene sequences supported that Homoeostrichus species are closely related to
Exallosorus species and clearly separated from each others in addition to Zonaria
species. CONCLUSIONS: Homoeostrichus formosana sp. nov. can now be clearly
distinguished from E. harveyanus and Japanese H. flabellatus.
PMID- 28510857
TI - Treeline dynamics in response to climate change in the Min Mountains,
southwestern China.
AB - BACKGROUND: Abies faxoniana is the dominant plant species of the forest ecosystem
on the eastern edge of Qinghai-Tibet Plateau, where the treeline is strongly
defined by climate. The tree-ring chronologies and age structure of Abies
faxoniana were developed in the treeline ecotones on the northwestern and
southeastern aspects of the Min Mountains in the Wanglang Nature Reserve to
examine the treeline dynamics of recent decades in response to climate change.
RESULTS: On the northwestern aspect, correlation analysis showed that the radial
growth was significantly and positively correlated with precipitation in current
January and monthly mean temperature in current April, but significantly and
negatively correlated with monthly mean temperature in previous August. On the
southeastern aspect, the radial growth was significantly negatively correlated
with monthly mean temperature in previous July and August. CONCLUSIONS: The
different responses of radial growth to climatic variability on both the aspects
might be mainly due to the micro-environmental conditions. The recruitment
benefited from the warm temperature in current April, July and September on the
northwestern aspect. The responses of radial growth and recruitment to climatic
variability were similar on the northwestern slope. Recruitment was greatly
restricted by competition with dense bamboos on the southeastern aspect.
PMID- 28510858
TI - Synotis xinningensis (Asteraceae), a new species from Hunan, China.
AB - BACKGROUND: Synotis is one of the several genera within Senecioneae (Asteraceae)
with more than 40 species that are mainly distributed in China or in the Sino
Himalayan region. During a botanical expedition in central and southwestern China
in 2011, we found an unusual population of Synotis in southwestern Hunan
Province. To determine the taxonomic identity of the population, we carried out
gross-morphological, floral micromorphological, and cytological observations.
RESULTS: Our gross-morphological observations have shown that the population is
most similar to Synotis changiana Y. L. Chen, but readily distinguishable in the
discoid capitula (vs. radiate), and in the bracts of calyculus 9-10 (vs. 6-8), 6
7 mm long (vs. 3-4 mm). The floral micromorphological observations on the
population and S. changiana agree with previous reports for other species of
Synotis. The chromosomes of the population are counted to be 2n = 40 + 0-1B. Its
karyotype is formulated as 2n = 22m + 14sm + 4st. CONCLUSIONS: The population is
determined to represent a new species, i.e. Synotis xinningensis M. Tang & Q. E.
Yang, which is described herein. The new species belongs to Synotis ser. Synotis.
PMID- 28510859
TI - Deep cytogenetics analysis reveals meiotic recombination depletion in species of
Senecio (Asteraceae).
AB - BACKGROUND: Senecio is the largest genus in the Asteraceae family growing in all
environments around the world. It displays taxonomic and systematical
difficulties. Cytogenetic knowledge of this genus is ancient, scarce and mainly
restricted to chromosome number records. RESULTS: In this study we analyzed
chromosome number, meiotic configuration, bivalent morphology, meiotic behavior
and pollen grain stainability on 100 accessions of 27 different polyploid Senecio
L. sect Senecio entities. Median, standard deviation and mode were calculated for
number and position of chiasmata and meiotic recombination was statistically
evaluated. Although high frequency of multivalents and associated meiotic
irregularities are expected in high polyploids, bivalents predominance and,
consequently, regular meiosis were observed, with normal sporogenesis and high
pollen grain stainability. CONCLUSION: Depletion in the total chiasmata was
significant only in some species but the terminal position was preferential in
all the entities analyzed, indicating significant reduction in recombination. The
regular meiosis observed suggest that intra and intergenomic reorganization
process occur quickly and efficiently in this genus. Mechanisms of
diploidization, common to all polyploids, are reinforced by the strong reduction
in crossing-over rushing polyploids stabilization.
PMID- 28510860
TI - The extent of Ds1 transposon to enrich transcriptomes and proteomes by
exonization.
AB - BACKGROUND: Exonization is an event which an intronic transposed element (TE)
provides splice sites and leads to alternatively spliced cassette exons. Without
disrupting of the inserted gene's function, TEs can expand the proteome diversity
by adding the splice variant that encodes a different, yet functional protein.
Previously, we found that the main contribution of Ds exonization for gene
divergence is not providing genetic messages but incorporating the intron
sequences with different reading frame patterns to enrich the plant proteome.
Ds1, another member of Ac/Ds transposon system, differs from Ds by providing 3
splice donor sites and 2 acceptor sites for alternative splicing, which may
greatly increase the extent for proteome expansion. RESULTS: In this study, we
performed a genome-wide survey of Ds1 exonization events to assess its extent to
enrich proteomes in plants. Each Ds1 insertion yielded 11 transcript isoforms by
integrating the splice donor and/or acceptor sites, which composed a bulk of all
exonized transcript orthologs from the dicot Arabidopsis thaliana and the monocot
Oryza sativa (rice). The exonized transcripts were analyzed by the locations of
the termination codon (PTC) and the putative targets for the nonsense-mediated
decay (NMD) pathway were then excluded. Compared with the Ds element, Ds1 harbors
more contents of non-NMD transcripts for protein isoforms. CONCLUSIONS: The
contribution of Ds1 exonization for gene divergence is incorporating the intron
sequences with different reading frame patterns to enrich the plant proteome. All
these simulation results direct new experimental analysis at the molecular level.
PMID- 28510862
TI - Primulina cardaminifolia (Gesneriaceae), a rare new species from limestone areas
in Guangxi, China.
AB - BACKGROUND: Primulina cardaminifolia Yan Liu & W.B. Xu (Gesneriaceae), a distinct
new species with imparipinnate leaves, is described and illustrated from a
limestone valley in Guangxi Zhuangzu Autonomous Region, China. To assure its
generic placement and phylogenetic affinity, phylogenetic analyses were performed
using DNA sequences of nuclear ITS and chloroplast trnL-F intron spacer region.
Additionally, somatic chromosome number was counted and pollen stainability was
tested. RESULTS: Phylogenetic analyses support its placement in Primulina;
however, two phylogenetically distinct ITS sequence types were detected,
suggesting a probable hybrid origin. Its pollen stainability is 100% and its
chromosome number, 2n = 36, is congruent with all known counts of diploid species
of the genus. CONCLUSION: All available data support the recognition of the new
species Primulina cardaminifolia and suggest that it could have derived from
homoploid hybrid speciation. Color plates, line drawings and a distribution map
are provided to aid in identification.
PMID- 28510861
TI - Ectopic expression of OsMADS45 activates the upstream genes Hd3a and RFT1 at an
early development stage causing early flowering in rice.
AB - BACKGROUND: The rice gene, OsMADS45, which belongs to the MADS-box E class gene,
participates in the regulation of floral development. Previous studies have
revealed that ectopic expression of OsMADS45 induces early flowering and
influences reduced plant height under short-day (SD) conditions. However, the
regulation mechanism of OsMADS45 overexpression remains unknown. We introduce an
OsMADS45 overexpression construct Ubi:OsMADS45 into TNG67 plants (an Hd1 (Heading
date 1) and Ehd1 (Early heading date 1) defective rice cultivar grown in Taiwan),
and we analyzed the expression patterns of various floral regulators to
understand the regulation pathways affected by OsMADS45 expression. RESULTS: The
transgenic rice exhibit a heading date approximately 40 days earlier than that
observed in TNG67 plants, and transgenic rice display small plant size and low
grain yield. OsMADS45 overexpression did not alter the oscillating rhythm of the
examined floral regulatory genes but advanced (by approximately 20 days) the up
regulate of two florigens, Hd3a (Heading Date 3a) and RFT1 (RICE FLOWERING LOCUS
T1) and suppressed the expression of Hd1 at the juvenile stage. The expression
levels of OsMADS14 and OsMADS18, which are two well-known reproductive phase
transition markers, were also increased at early developmental stages and are
believed to be the major regulators responsible for early flowering in OsMADS45
overexpressing transgenic rice. OsMADS45 overexpression did not influence other
floral regulator genes upstream of Hd1 and Ehd1, such as OsGI (OsGIGANTEA),
Ehd2/Osld1/RID1 and OsMADS50. CONCLUSION: These results indicate that in
transgenic rice, OsMADS45 overexpressing ectopically activates the upstream genes
Hd3a and RFT1 at early development stage and up-regulates the expression of
OsMADS14 and OsMADS18, which induces early flowering.
PMID- 28510863
TI - Xiphopterella devolii (Polypodiaceae), a new species and newly recorded genus in
Taiwan.
AB - BACKGROUND: Grammitid ferns are a tropical monophyletic clade nested in
Polypodiaceae, containing more than 20 genera and more than 750 species. Many of
them also grow in Taiwan. During the survey of recent two decades, an unknown
grammitid fern was discovered and the taxonomic treatment is given herein.
RESULTS: A new species, collected from Taiwan, is recognized and named, i.e.,
Xiphopterella devolii S. J. Moore, Parris, & W. L. Chiou. The holotype is
deposited in TAIF, and isotypes are in HAST, K, L, US, and TNS. It is also
distributed on SE & S China. The genus Xiphopterella is also a new record to
Taiwan. CONCLUSION: A new species, Xiphopterella devolii S. J. Moore, Parris, &
W. L. Chiou is documented herein. The Xiphopterella is a new recorded genus in
Taiwan and is first found beyond Malesia regions.
PMID- 28510865
TI - Asarum pubitessellatum, sp. nov. (sect. Heterotropa, Aristolochiaceae) from
Taiwan based on morphological and palynological evidence.
AB - BACKGROUND: Recently, we discovered an unknown Asarum from Taiwan which is
closely related to A. crassisepalum S.F. Huang, T.H. Hsieh and T.C. Huang and A.
taipingshanianum S.F. Huang, T.H. Hsieh and T.C. Huang by sharing a thick leaf
blade, spreading perianth-lobes and a conical to cylindrical perianth-tube. We
compared it with other related species and identified this plant as a new
species. RESULTS: This new species differs distinctly from the above two related
species by having larger plant body, shortened rhizomes and an inner surface of
the perianth-tube that is covered with numerous simple trichomes (vs. glandular
trichomes). The pollen tectum in this new species is perforate, which differs
from the incomplete reticulate with small supratectate granules in A.
crassisepalum and the compact rugulate with small supratectate granules in A.
taipingshanianum. Furthermore, these three species are geographically separated
from one another. CONCLUSIONS: Asarum pubitessellatum C.T. Lu & J.C. Wang, a new
species is described and illustrated. The trichomes on the inner surface of the
perianth-tube and pollen micromorphology were the valuable characters in the low
level classification of Heterotropa species in Taiwan.
PMID- 28510866
TI - Calanthe xhsinchuensis (Orchidaceae), a new natural hybrid from Taiwan.
AB - BACKGROUND: Natural hybridization in plants is a vital mechanism of speciation.
Calanthe arisanensis and C. sieboldii occur in the same habitat in northern
Taiwan, where there are a number of plants whose morphologically characters are
similar in between of these two species. In this report, a new natural hybrid,
Calanthe species - C. xhsinchuensis Y.I. Lee putatively derived from the natural
hybridization of C. arisanensis and C. sieboldii was described and illustrated.
Besides, somatic chromosome number was counted. RESULTS: The morphological and
histological data of flowers, capsules, roots and leaves of C. xhsinchuensis show
an intermediate condition between its putative parents. The chromosome number, 2n
= 40, is also congruent with its putative parents. Color plates and line drawings
are provided to aid in identification. CONCLUSION: Base on the morphological
characteristics of reproductive and vegetative organs, and the distributions of
putative parents, it is proposed that C. xhsinchuensis is a natural hybrid
between C. arisanensis Hayata and C. sieboldii Decaisne ex Regel.
PMID- 28510864
TI - Galactolipid biosynthesis in flowers.
AB - Phospholipids represent the highly conserved structural basis of biological
membranes from bacteria to humans. However, plants and other photoautotrophic
organisms are unique in using non-phosphorus galactolipids as primary components
of their photosynthetic membranes. In light of the biomass of green tissues as
compared with that of the overall plant body and the highly stacked thylakoid
membrane structures in chloroplasts, galactolipids are the most abundant membrane
lipids on the earth. Historically, the roles of galactolipids have been studied
mainly in relation to photosynthesis, and recent advances in molecular biology
with Arabidopsis and other model organisms have revealed an essential role of
galactolipids in photosynthesis. However, these galactolipids are also abundant
in non-photosynthetic organs, especially flowers, which suggests their distinct
role apart from photosynthesis. The aim of this mini-review is to describe
distinct biochemical properties of flower galactolipids and possible new roles,
with a summary of the current understanding of galactolipid biosynthesis in
Arabidopsis.
PMID- 28510867
TI - Role of 5-aminolevulinic acid in the salinity stress response of the seeds and
seedlings of the medicinal plant Cassia obtusifolia L.
AB - BACKGROUND: Soil salinity, one of the major abiotic stresses affecting
germination, crop growth, and productivity, is a common adverse environmental
factor. The possibility of enhancing the salinity stress tolerance of Cassia
obtusifolia L. seeds and seedlings by the exogenous application of 5
aminolevulinic acid (ALA) was investigated. RESULT: To improve the salinity
tolerance of seeds, ALA was applied in various concentrations (5, 10, 15, and 20
mg/L). To improve the salinity tolerance of seedlings, ALA was applied in various
concentrations (10, 25, 50, and 100 mg/L). After 10 mg/L ALA treatment,
physiological indices of seed germination (i.e., germination vigor, germination
rate, germination index, and vigor index) significantly improved. At 25 mg/L ALA,
there was a significant protection against salinity stress compared with non-ALA
treated seedlings. Chlorophyll content, total soluble sugars, free proline, and
soluble protein contents were significantly enhanced. Increased thiobarbituric
acid reactive species and membrane permeability levels were also inhibited with
the ALA treatment. With the treatments of ALA, the levels of chlorophyll
fluorescence parameters, i.e., the photochemical efficiency of photosystem II
(Fv/Fm), photochemical efficiency (Fv'/Fm'), PSII actual photochemical efficiency
(PhiPSII), and photochemical quench coefficient (qP), all significantly
increased. In contrast, the non-photochemical quenching coefficient (NPQ)
decreased. ALA treatment also enhanced the activities of superoxide dismutase,
peroxidase, and catalase in seedling leaves. The highest salinity tolerance was
obtained at 25 mg/L ALA treatment. CONCLUSION: The plant growth regulator ALA
could be effectively used to protect C. obtusifolia seeds and seedlings from the
damaging effects of salinity stress without adversely affecting plant growth.
PMID- 28510868
TI - Immunocytochemical localization of saikosaponin-d in vegetative organs of
Bupleurum scorzonerifolium Willd.
AB - BACKGROUND: Saikosaponin-d (SSd) is an important active component of Bupleurum
scorzonerifolium Willd., a traditional Chinese medicinal herb. Thus far, the
biosynthetic pathway and biosynthetic site of saikosaponins in Bupleurum are
largely unknown. The cellular localization of SSd will help in understanding
saikosaponin biosynthesis and regulation. RESULTS: In this study, we characterize
for the first time the localization of SSd in B. scorzonerifolium tissues and
cells using histochemistry and immunoelectron microscopy. The results show that
the saikosaponin distribution in different plant organs changes as they mature.
The number of SSd gold particles distinctly differed among the roots, stems, and
leaves, with the particles mainly concentrated in the roots. The gold particles
were mainly observed in vacuoles, with a few particles in the protoplasm; hence,
SSd is mainly stored in vacuoles. CONCLUSIONS: We speculate that saikosaponins
are mainly synthesized via the mevalonate pathway in the protoplasm in young
organs, and then transported to the central vacuole by the endoplasmic reticulum
(ER) or the fusion of vacuoles, to protect plants from self-poisoning with the
accumulation of more saikosaponins.
PMID- 28510869
TI - DNA barcode assessment of Gracilaria salicornia (Gracilariaceae, Rhodophyta) from
Southeast Asia.
AB - BACKGROUND: DNA barcoding is becoming a widely applied tool for the quick and
accurate identification of species. The evolution of the mitochondrial cytochrome
c oxidase subunit I (COI) gene is sufficiently rapid to allow discrimination
between closely related species and biogeographic subgroups within species.
Gracilaria salicornia was originally described as being from Manila, the
Philippines, and is distributed throughout Asia and the Indian Ocean. To more
accurately define this species and its genetic diversity owing to the confusion
of identification historically, DNA barcoding using the 5' end of the COI gene of
the mitochondrial genome was applied to specimens collected from the Philippines,
Malaysia, Thailand, China, and Japan, and they were compared to other gracilarian
species. RESULTS: Within species, the COI marker yielded two clusters with
nucleotide divergences of 0.0-1.3%. This divergence is slightly higher than the
typical intraspecific variation for red algae. A total of eight COI haplotypes
were found for G. salicornia, comprising the following groups: H1-H3 from the
Philippines; H4 from Okinawa in Japan; H5-H7 from Malaysia, Thailand, and China;
and H8 from Thailand. CONCLUSION: Although this work concentrated on a limited
geographical region of a widespread taxon, the data shows intraspecific molecular
divergences in G. salicornia and provides further evidence that DNA barcodes are
useful tools for identifying species boundaries and examining biogeographical
haplotypes for the genus Gracilaria.
PMID- 28510870
TI - Factors affecting ozone sensitivity of tobacco Bel-W3 seedlings.
AB - BACKGROUND: Since 1962, the tobacco variety Nicotiana tabacum cv. Bel-W3 has been
used worldwide as an ozone (O3) bio-indicator. The use of indicator plants to
monitor O3 pollution has proven problematic when trying to correlate the severity
of injury to ambient O3 concentration. The aim of the present study was to study
factors affecting the O3 sensitivity of Nicotiana tabacum cv. Bel-W3 seedlings.
RESULTS: In chronic O3 pre-exposure tests, tobacco plants were cultured from
seeds in charcoal-filtered air (CF) and noncharcoal-filtered ambient air (NF) for
21 days. During these periods, the mean O3 concentrations of the CF and NF
treatments were 5.5 +/- 0.2 and 14.7 +/- 0.4 ppb h-1, respectively (p < 0.001).
At the end of the culturing period, no O3-induced foliar injury was observed in
any of the plants. The O3 sensitivity of the tobacco plants was determined by
exposing the plants to 150 ppb O3 for 8 hours in a fumigation chamber. The leaf
injury index percentages (LII%) of indicator plants via the CF and NF treatments
were 58.0 +/- 3.2% and 43.1 +/- 4.0%, respectively (p < 0.01). Twenty-one-day-old
tobacco seedlings grown in NF air were used to test the effects of exposed leaves
on O3 sensitivity. After removing the cotyledons and all true leaves, the NF
seedlings with their apical buds intact were transferred to CF air. After another
7 days of culturing, the newly developed leaves were approximately 1 cm in
length. After O3 treatment, the LII% values of the newly developed leaves from
the untreated and defoliated seedlings were 2.5 +/- 1.7% and 27.6 +/- 1.3%,
respectively (p < 0.001). In acute O3 exposure tests, 21-day-old seedlings grown
in CF air were fumigated with 150 ppb O3 for 8 hours in one day or for 4
hours/day in two consecutive days. The LII% values for the two groups were 63.5
+/- 7.4% and 20.1 +/- 4.3%, respectively (p < 0.001). CONCLUSIONS: The present
findings suggest that plant pre-exposure to O3 is a critical factor influencing
O3 sensitivity and that exposed leaves obtain acquired tolerance against O3
injury later on.
PMID- 28510871
TI - Lemon protein disulfide isomerase: cDNA cloning and biochemical characterization.
AB - BACKGROUND: Protein disulfide isomerases (PDIs), a family of structurally related
enzymes, aid in protein folding by catalyzing disulfide bonds formation,
breakage, or isomerization in newly synthesized proteins and thus. RESULTS: A
ClPDI cDNA (1828 bp, GenBank accession HM641784) encoding a putative PDI from
Citrus limonum was cloned by polymerase chain reaction (PCR). The DNA sequence
encodes a protein of 500 amino acids with a calculated molecular mass of 60.5
kDa. The deduced amino acid sequence is conserved among the reported PDIs. A 3-D
structural model of the ClPDI has been created based on the known crystal
structure of Homo sapiens (PDB ID: 3F8U_A). The enzyme has two putative active
sites comprising the redox-active disulfides between residues 60-63 and 405-408
(motif CGHC). To further characterize the ClPDI, the coding region was subcloned
into an expression vector pET-20b (+), transformed into E. coli Rosetta
(DE3)pLysS, and recombinant protein expressed. The recombinant ClPDI was purified
by a nickel Sepharose column. PDI's activity was assayed based on the ability of
the enzyme to isomerize scrambled RNase A (sRNase A) to active enzyme. The KM,
kcat and kcat/KM values were 8.3 * 10-3 MUM, 3.0 * 10-5 min-1, and 3.6 * 10-1 min
1 mM-1. The enzyme was most active at pH 8. CONCLUSIONS: The advantage of this
enzyme over the PDI from all other sources is its low KM. The potential
applications of this PDI in health and beauty may worth pursuing.
PMID- 28510872
TI - Improving initial infectivity of the Turnip mosaic virus (TuMV) infectious clone
by an mini binary vector via agro-infiltration.
AB - BACKGROUND: The in vivo infectious clone of Turnip mosaic virus (TuMV), p35S
TuMV, was used on plant pathology research for many years. To activate p35S-TuMV,
the plasmid was mechanically introduced to the local lesion host Chenopodium
quinoa. However, low infectivity occurred when the TuMV from C. quinoa was
transferred to the systemic host Nicotiana benthamiana. RESULTS: To increase the
efficiency of initial infectivity on N. benthamiana, the expression of the TuMV
infectious clone by a binary vector that directly activates viral RNA through
agro-infiltration is considered to be a good alternative. The size of the binary
vector by agro-infiltration is usually large and its backbone has numerous
restriction sites that increase difficulty for construction. In this study, we
attempted to construct a mini binary vector (pBD003) with less restriction sites.
The full-length cDNA of TuMV genome, with or without green fluorescence protein,
was inserted in pBD003 to generate pBD-TuMV constructs, which were then
individually introduced to N. benthamiana plants by agro-infiltration. Symptom
development and ELISA positivity with TuMV antiserum indicated that the pBD-TuMV
constructs are infectious. Moreover, the initial infectivity of a mild strain
TuMV-GK, which contains an R182K mutation on HC-Pro, constructed in the pBD003
vector was significantly increased by agro-infiltration. CONCLUSION: Thus, we
concluded that the newly constructed mini binary vector provides a more feasible
tool for TuMV researches in areas, such as creating a mild strain for cross
protection, or a viral vector for foreign gene expression. In addition, the
multiple cloning sites will be further cloned in pBD003 for convenience in
constructing other viral infectious clones.
PMID- 28510873
TI - Enhanced tolerance of transgenic potato plants expressing choline oxidase in
chloroplasts against water stress.
AB - BACKGROUND: Glycinebetaine, whose biosynthesis could be catalyzed by choline
oxidase (COD), is an extremely efficient compatible solute for scavenging
oxidative stress-inducing molecules and protecting the photosynthetic system in
plants. To study the effects of the codA transgene for choline oxidase on the
drought resistance and recovery, a transgenic potato cultivar (SC) bearing codA
gene and a non-transgenic (NT) control cultivar were raised in pots under
moderate and severe drought stress. The experiment was constituted by a two-day
pretreatment with 20% PEG and a four-day-water stress combined with two-day
recovery treatment. RESULTS: Under the four-day-water stress, plants were
provided with normal water condition, 10% or 20% polyethylene glycol. The results
of pretreatment showed an expression of codA gene in transgenic potato and an
accumulation of glycine betaine (GB); leaf water potential was higher in SC than
in NT. In the stress-recovery-treatment, SC showed stronger antioxidant ability,
more efficient photosynthetic system, higher chlorophyll content, lower
malondialdehyde content and better recovery from water deficit stress than NT.
CONCLUSION: Although this work concentrated on the short-term water stress and
recover treatments on transgenic potato plants with the over-expression of CodA
gene and its control line. The datas shows that the exogenous codA gene provided
potato a stronger drought resistance and recovery ability.
PMID- 28510874
TI - The NPR1 ortholog PhaNPR1 is required for the induction of PhaPR1 in Phalaenopsis
aphrodite.
AB - BACKGROUND: Systematic acquired resistance (SAR) is an effective broad-spectrum
defense mechanism that confers long-lasting protection against biotrophic
pathogens trough defense related salicylic acid (SA) signaling. Gene(s) involved
in SAR have been extensively studied in dicot plants; however, remains largely
unresolved in monocot plants. NPR1, an evolutionary conserved gene, plays a
central role in SAR, and PR-1 is widely used as a marker for effective SA
signaling. RESULTS: We identified NPR1 and PR-1 homologous genes, PhaNPR1 and
PhaPR1, from an economically important orchid, Phalaenopsis aphrodite, and
characterized their roles in SA signaling and Cymbidium mosaic virus (CymMV)
resistance. A phylogenetic analysis of NPR1 homologs showed that these genes
appear to have evolved before angiospermy. Similar to Arabidopsis NPR1, PhaNPR1
was only moderately induced upon SA treatment and CymMV infection. Although
PhaPR1 shows only 36% identity with AtPR1, its promoter shared conserved elements
with those of other PR-1 genes, and it was induced upon SA treatment and CymMV
infection. After CymMV infection, silencing on PhaNPR1 also reduced PhaPR1
expression; however, CymMV accumulation was not affected. CONCLUSIONS: In
conclusion, after virus infection, PhaNPR1 is required for PhaPR1 induction, but
plays little role in defense against CymMV.
PMID- 28510875
TI - Morphological, anatomical and physiological leaf traits of Q. ilex, P. latifolia,
P. lentiscus, and M. communis and their response to Mediterranean climate stress
factors.
AB - BACKGROUND: Limitations to plant growth imposed by the Mediterranean climate are
mainly due to carbon balance in response to stress factors. In particular, water
stress associated to high air temperature and irradiance in summer causes a
marked decrease in CO2 assimilation. Air temperature sensitivity of
photosynthesis (PN) differs from that of leaf respiration (RD). PN often
decreases sharply at temperature above its optimum while RD increases
exponentially over short term rises in temperature. Nevertheless, the impact of
water deficit on RD is still far from clear with reports in literature including
decreases, maintenance or increases in its rates. The ratio RD/PN can be
considered a simple approach to leaf carbon balance because it indicates the
percentage of photosynthates that is respired. RESULTS: The results underline
different morphological, anatomical and physiological traits of the evergreen
species co-occurring in the Mediterranean maquis which are indicative of their
adaptive capability to Mediterranean stress factors. The ratio RD/PN varies from
0.15 +/- 0.04 in autumn, 0.24 +/- 0.05 in spring through 0.29 +/- 0.15 in winter
to 0.46 +/- 0.11 in summer. The lower RD/PN in autumn and spring underlines the
highest PN rates during the favorable periods when resources are not limited and
leaves take in roughly three to five times more CO2 than they lose by
respiration. On the contrary, the highest RD/PN ratio in summer underlines the
lowest sensitivity of respiration to drought. Among the considered species,
Quercus ilex and Pistacia lentiscus have the largest tolerance to low winter
temperatures while Phillyrea latifolia and Myrtus communis to drought, and
Phillyrea latifolia the highest recovery capability after the first rainfall
following drought. CONCLUSIONS: The Mediterranean evergreen specie shows a
different tolerance to Mediterranean climate stress factors. The predicted global
warming might differently affect carbon balance of the considered species, with a
possible change in Mediterranean shrublands composition in the long-term.
Understanding the carbon balance of plants in water limited environments is
crucial in order to make informed land management decisions. Moreover, our
results underline the importance of including seasonal variations of
photosynthesis and respiration in carbon balance models.
PMID- 28510877
TI - Recircumscription of Begonia sect. Baryandra (Begoniaceae): evidence from
molecular data.
AB - BACKGROUND: Begonia sect. Diploclinium is a 'dust-bin' section for species
retaining pleisiomorphic characters and lacking novel synapomorphic characters
used to delimit other Asian sections in Begonia. Part of this large and
polymorphous section is transferred to Begonia sect. Baryandra in a move towards
a more natural classification for the genus. RESULTS: Phylogenetic analysis of
nuclear ribosomal ITS DNA sequences show a strongly supported monophyletic group
containing Philippine and Bornean species previously in Begonia sect.
Diploclinium, and the type of Begonia sect. Baryandra, B. oxysperma. This clade
forms the basis for the now much-expanded Begonia sect. Baryandra, which as
defined here contains 49 species and has its centre of diversity in the
Philippines. CONCLUSIONS: A natural classification for a much expanded Begonia
sect. Baryandra has been provided. This paper highlights the feasibility of
moving towards a natural classification of Asian Begonia step by step as
information comes to light through building upon previous framework phylogenies
with denser sampling.
PMID- 28510876
TI - Antimicrobial activities of stearidonic and gamma-linolenic acids from the green
seaweed Enteromorpha linza against several oral pathogenic bacteria.
AB - BACKGROUND: We found that the edible green seaweed Enteromorpha linza displayed
potent antimicrobial activity against Prevotella intermedia and Porphyromonas
gingivalis. To elucidate the active component of E. linza, isolation procedures
were performed. RESULTS: The main active compound was isolated by polarity
fractionation, Sephadex LH-20 gel chromatography, and reverse-phase high
performance liquid chromatography (RP-HPLC). The active compounds were eluted at
isocratic 95% acetonitrile by RP-HPLC and identified as unsaturated fatty acids,
stearidonic acid (SA, C18:4 n-3) and gamma-linolenic acid (GLA, C18:3 n-6) by gas
chromatography-mass spectrometry, 1H nuclear magnetic resonance (NMR)
spectroscopy, and 13C NMR spectroscopy. The yields of SA and GLA from dried
seaweed tissue were 6.33 * 10-3% and 6.47 * 10-3%, respectively. The minimal
inhibitory concentration values of SA and GLA were 39.06 MUg/mL against P.
intermedia and 9.76 MUg/mL against P. gingivalis, respectively. SA and GLA were
also active against several other oral pathogens, including Aggregatibacter
actinomycetemcomitans, Candida albicans, Fusobacterium nucleatum subsp. vincenti,
and Streptococcus mutans, at micromolar concentrations. CONCLUSIONS: These data
suggest that the E. linza extracts SA and GLA are useful antimicrobial agents for
the prevention and/or treatment of periodontitis.
PMID- 28510879
TI - Cryopreservation the seeds of a Taiwanese terrestrial orchid, Bletilla formosana
(Hayata) Schltr. by vitrification.
AB - BACKGROUND: The cryopreservation of orchid seeds is an important conservation
method, studies of the effects of cryopreservation on the seeds of wild orchids
are scant. This investigation was to establish a method for the vitrification and
cryopreservation of seeds of B. formosana that may be suitable for the long term
storage of Taiwan native orchid germplasm for conservation purposes. RESULTS: The
germination rate and morphological stability of seeds from spontaneous-dehiscent
capsules of Bletilla formosana (Hayata) Schltr. were evaluated after
cryopreservation by vitrification. The germination rates of cryopreserved seeds
varied according to immersion time and the vitrification method used. Seeds that
were dehydrated by immersion in loading solution (LS; 2.0 M glycerol, 0.4 M
sucrose) for 10 min to 30 min then transferred to plant vitrification solution 2
(PVS2) for 30 min prior to freezing in liquid nitrogen (LN) showed significantly
higher germination rates than seeds immersed in PVS2 only. The optimal immersion
times were 10 min for LS and 30 min for PVS2, resulting in an in vitro
germination rate of 91%. Germination was not observed for cryopreserved seeds
that were dehydrated by immersion in LS only. Seed viabilities and germination
rates did not vary significantly for cryostorage times from 10 minutes to 1 year.
CONCLUSIONS: This study improve, an efficient protocol was established that
maintained seed viability and enhanced the germination rates of seeds, compared
with previously described cryopreservation methods, and the germinated seeds
showed normal morphology of both vegetative and reproductive organs.
PMID- 28510878
TI - Activation tagging in Salvia miltiorrhiza can cause increased leaf size and
accumulation of tanshinone I and IIA in its roots.
AB - BACKGROUND: Salvia miltiorrhiza Bunge (Danshen), an important herb in traditional
Chinese medicine, is commonly used for treatment of cardiovascular diseases. One
of the major bioactive constituents of Danshen, diterpenoid tanshinone, has been
proved with pharmacological properties and have the potential to be a new drug
candidate against various diseases. In our previous study, we have established an
activation tagging mutagenesis (ATM) population of callus lines of S.
miltiorrhiza Bunge by Agrobacterium- mediated transformation. RESULTS: In the
present study, we have identified ATM transgenic Salvia plant (SH41) with
different leaf morphology and more tanshinones in its roots. The transgenic
background of SH41 was identified by PCR (using hpt II primers) and Southern
blots. PCR analysis showed a single band of hpt II gene and Southern blot
analysis showed single insertion in SH41. External appearance of ATM transgenic
SH41 was observed with broader leaves comparing to non-transformed plants. More
healthy trichomes as well as bigger and wobbly guard cells and stomata were
observed in SH41 by scanning electron microscopy (SEM). Quantitative analysis of
active compounds in SH41 roots revealed a significant increase in tanshinone I
(3.7 fold) and tanshinone IIA (2 fold) contents as compared to the wild plant.
CONCLUSIONS: We have generated an activation tagged transgenic Salvia plant
(SH41) with different leaf morphology and high diterpenes content in its roots.
The increased amount of tanshinones in SH41 will definitely offer a route for
maximizing the benefits of this plant in traditional Chinese herbal medicines.
The present report may also facilitate the application of ATM for genetic
manipulation of other medicinal crops and subsequent improved metabolite
contents.
PMID- 28510880
TI - Biodiversity of soil algae in the farmlands of mid-Taiwan.
AB - BACKGROUND: Very little information is available about soil algae in Taiwan. In
this study, we investigated for the first time the soil algae inhabiting five
types of farmland in mid-Taiwan: rice paddies, vegetable farms, tea plantations,
sugar cane farms, and orchards. RESULTS: Sixty-four taxa belonging to 33 genera
of cyanobacteria, diatoms, green algae, and euglenoids were identified on the
basis of fine structures observed under optical and electron microscopes and rDNA
sequencing. The majority of the isolates were of the genera Oscillatoria,
Navicula, Nitzschia, and Pinnularia. Five species were reported for the first
time in Taiwan, namely Microcoleus paludosus, M. subtorulosus, Navicula
subminuscula, Nitzschia levidensis, and Ni. pusilla. CONCLUSIONS: The
distribution and diversity of these species was shown to be strongly dependent on
habitat, with the highest diversity of green algae in the orchards, a fairly high
diversity of diatoms and cyanobacteria in the rice paddies, and a relatively low
diversity in the tea plantations and sugar cane farms. The humidity and acidity
were the most important environmental factors influencing the diversity of soil
algae in these farmlands.
PMID- 28510881
TI - Structural and functional alterations in photosynthetic apparatus of plants under
cadmium stress.
AB - Cadmium is a potentially toxic heavy metal that hampers plant productivity by
interfering with their photochemistry. Cd causes disturbances in a range of
physiological processes of plants such as photosynthesis, water relations, ion
metabolism and mineral uptake. Cd pronouncedly affects photosynthesis by
alteration of its vital machinery in all aspects. Photosynthesis is a well
organised and sequential process fundamental to all green plants and
microorganisms which involves various components, including photosynthetic
pigments and photosystems, the electron transport system and CO2 reduction
pathways. Any damage at any level caused by Cd, critically affects overall
photosynthetic capacity. Present review focuses on key effects of Cd on
photosynthetic apparatus including chloroplast structure, photosynthetic
pigments, Chl-protein complexes and photosystems resulting in overall decrease in
efficiency of carbon assimilation pathway.
PMID- 28510882
TI - Characterization of differential expression and leader intron function of
Arabidopsis atTOC159 homologous genes by transgenic plants.
AB - BACKGROUND: Accurate import of thousands of nuclear-encoded proteins is an
important step in plastid biogenesis. However, the import machinery of cytosolic
precursor proteins to plastids relies on the Toc and Tic (translocons on the
outer envelope and inner envelope membrane of chloroplasts) complexes. Toc159
protein was identified in pea (Pisum sativum) as a major receptor for the
precursor proteins. In Arabidopsis thaliana, four psToc159 homologs are
identified, termed atToc159, atToc132, atToc120 and atToc90. The expression of
these protein-encoding genes has to be properly regulated, because their gene
products must be correctly integrated to appropriate apparatus to perform their
functions. RESULTS: In order to elucidate the regulatory mechanisms of atTOC159
homologous gene expression, transgenes containing various lengths of the upstream
regulatory sequences of atTOC159/atTOC132/atTOC120/atTOC90 and GUS coding
sequence were transferred to wild type Arabidopsis. In accordance with the
analysis of GUS activity in these transgenic plants at various developmental
stages, these homologous genes had distinct expression patterns. AtTOC159 and
atTOC90 are preferentially expressed in above-ground tissues, such as cotyledons
and leaves. In mature roots, atTOC159 and atTOC132 are expressed at higher
levels, while atTOC120 and atTOC90 are expressed at the basal level. All four
genes have increased expression level during flower and fruit development,
particularly a remarkably high expression level of atTOC159 in later stage of
fruit development. Furthermore, leader intron in the 5' UTR induces the
expression level of atTOC159 members in a tissue-specific manner. This is able to
up-regulate the atTOC120 expression in roots/leaves/flowers, and the atTOC90
expression in cotyledons/leaves/anthers. CONCLUSIONS: The differential expression
of atTOC159 gene members is essential during plastid development, because proper
atToc159 isoforms are required to import distinct proteins to the plastids of
different tissues.
PMID- 28510883
TI - Tissue culture-induced somaclonal variation of decreased pollen viability in
torenia (Torenia fournieri Lind.).
AB - BACKGROUND: Phenotypic and genotypic variations, collectively called somaclonal
variations, are induced during tissue culture. RESULTS: We studied the phenotypic
variation in pollen viability of regenerants of torenia after subculturing for
one to nine generations. We found that pollen viability of regenerants
continuously decreased with increasing subculture time. High concentrations of
plant growth regulators applied to the Murashige and Skoog (MS) medium also
resulted in diminished pollen viability. Furthermore, antibiotic application
during gene transformation also decreased pollen viability of the transformants.
However, the process of long-term culture did not significantly change pollen
viability. The mean methylation level of regenerants showed a 0.28% to 3.95%
decrease in seedlings subcultured in vitro for nine generations. Moreover, when
the ninth subcultured regenerants with reduced pollen vibility were recovered in
soil to get seeds, the pollen viability of seed-derive plants was similar to that
of the wild type. CONCLUSIONS: The results show that plant growth regulators,
antibiotics, and the number of subculture generations influence somaclonal
variations in torenia. The somaclonal variations in torenia may results from
epigenetic changes.
PMID- 28510884
TI - Novelties in Begonia sect. Coelocentrum: B. longgangensis and B. ferox from
limestone areas in Guangxi, China.
AB - BACKGROUND: The spectacular karst limestone landscape in Guangxi harbors high
level diversity and endemism of Begonia species, especially those of sect.
Coelocentrum. In continuation of our studies in this area, we report the
discovery of two attractive new species from southwestern Guangxi: Begonia
longgangensis and B. ferox. RESULTS: Begonia longgangensis resembles B. liuyanii,
also from Longgang Nature Reserve, in the broadly ovate to suborbicular leaf
blade, differing by the much smaller leaves, subglabrous leaf surface, pink
flowers, dichasial cymes and the remarkably long stolons sent out from rhizomes.
Unexpectedly, both diploid (2n = 30) and triploid counts (2n = 45) were observed
in plants collected from the type locality. Begonia ferox probably has the most
prominent bullate leaves for the genus. In this aspect, it is similar to B.
nahangensis reported from northern Vietnam recently, but is readily
distinguishable by the ovate, chartaceous leaves with an acuminate apex;
tomentose peduncle not exceeding petioles; and the much larger stature in
vegetative parts. A diploid count of 2n = 30 was determined for this unique new
species. CONCLUSIONS: All available data support the recognition of the two new
species. Begonia longgangensis has remarkably long stolons and B. ferox is
characterized by the prominent bullate leaves. Line drawings, color plates and
comparisons are provided to aid in identification of the novelties.
PMID- 28510885
TI - Floral biology, breeding system and pollination ecology of an endangered tree
Tetracentron sinense Oliv. (Trochodendraceae).
AB - BACKGROUND: Tetracentron sinense Oliv. is an endangered tree mainly distributed
in south-central China. The breeding system and pollination ecology of T. sinense
are unclear. With a conservation perspective, the floral biology, breeding system
and pollination ecology of Tetracentron sinense Oliv. were investigated, in order
to discuss the endangered factors related to pollination, and to provide
important information for its conservation. RESULTS: Our results revealed four
important aspects of the reproductive biology of T. sinense. 1) T. sinense
usually flowers by the beginning of June, and the flowering period of the
population is about two months, and the florescence of florets lasted for 15 to
24 days with delicate fragrance. 2) The pollen/ovule ratio is 720 +/- 28, and the
outcrossing index is three. Artificial pollination experiments showed that T.
sinense is self-compatible, with facultative xenogamy and no indication of
agamospermy. 3) The pollination syndrome is ambophily, and self-pollination plays
an important role in fruit production if wind and insect pollination is
unavailable. 4) Insect pollinators were predominantly represented by Coleoptera,
Diptera and Hymenoptera. Syrphid fly and bees were the main effective
pollinators. CONCLUSIONS: The results suggested that T. sinense exhibits a mixed
mating system, and autogamy in its breeding system may provide reproductive
assurance for the population maintenance. During flowering and pollination in
natural population, the decrease of population density and harsh environmental
condition might be one of crucial reasons resulting in endanger for this species.
PMID- 28510886
TI - Enhanced synthesis of andrographolide by Aspergillus niger and Penicillium
expansum elicitors in cell suspension culture of Andrographis paniculata (Burm.
f.) Nees.
AB - BACKGROUND: Andrographis paniculata (Burm. f.) Nees is an important medicinal
plant which has enormous applications in pharmaceutical industries. Cell
suspension culture of Andrographis paniculata (Burm. f.) Nees. was treated with
Aspergillus niger and Penicillium expansum elicitors to enhance the synthesis of
andrographolide, the bioactive constituent of A. paniculata. RESULT: The
elicitation treatment with fungal elicitors (A. niger and P. expansum) was
observed to be most suitable for eliciting andrographolide production in the
culture. The quantification of andrographolide was done using High Performance
Liquid Chromatography (HPLC) technique. A. niger extract (1.5 ml with10 days
treatment duration) revealed 6.94 fold increase in andrographolide content (132
MUg) which was higher than the control (19 MUg). P. expansum elicitor (0.6% with
8 days treatment duration) could reveal 6.23 fold enhancement in andrographolide
content (81.0 MUg) over control (13 MUg). CONCLUSION: The results obtained reveal
that the longer treatment duration is most favorable for the elicitation of
andrographolide using both the fungal elicitors.
PMID- 28510888
TI - Exogenous hydrogen peroxide increases dry matter production, mineral content and
level of osmotic solutes in young maize leaves and alleviates deleterious effects
of copper stress.
AB - BACKGROUND: The effects of exogenously applied H2O2 on growth, water status, the
mineral ion content (Na+, K+, Ca2+, Mg2+ and Cu2+), proline, total sugars and
soluble proteins were assessed in leaves of maize (Zea mays L.) cultivars,
Akpinar and Pegaso exposed to excess copper (0.5 mM). Seedlings were grown in
equal-sizes plastic pots and irrigated with Hoagland nutrient solution containing
H2O2 or/and copper. Different treatments taken for pot experiments were named as
the control (C), H2O2 treatment only (H2O2), excess Cu (Cu) and, Cu stress
combined with H2O2 pretreatment (Cu + H2O2). RESULTS: Treatment of H2O2 caused
the increases in growth, water content, mineral concentration, proline, total
sugar and soluble protein contents compared to the control groups in the leaves
of both cultivars. Yet excess copper caused reductions in the growth, leaf water
potential, Na+, K+, Ca+, Mg2+ concentrations and soluble protein levels but
increases in proline, total soluble sugars and Cu2+ contents compared to the
control group. Dry matter, leaf water potential and mineral content of Cu + H2O2
group revealed a lower decrease than Cu group ones. A higher increase was also
observed in proline and total sugar contents of Cu + H2O2 group than Cu group
ones in both cultivars. CONCLUSIONS: These data revealed that exogenous H2O2
might increase the dry matter production and the mineral ion distribution in
maize seedlings. Moreover, osmotic regulation might be involved in alleviation of
copper toxicity of maize leaves by pretreatment of H2O2.
PMID- 28510887
TI - Chemical and pharmacological investigation of micropropagated Hygrophila
pogonocalyx produced from leaf explants.
AB - BACKGROUND: An optimized method for indirect shoot organogenesis from the leaf
explants of Hygrophila pogonocalyx, a rare and endemic species in Taiwan, was
developed to supply enough quantity of plant materials for the first chemical and
pharmacological investigation. RESULTS: Incubation of the young leaves on
Murashige and Skoog (MS) medium supplemented with 6-benzylaminopurine (0.5 mg/l)
and indole-3-acetic acid (0.1 mg/l) resulted in the best multiplication rate for
organogenesis. The average number of adventitious buds per leaf was 22.8 +/- 1.9
after 8-week culture. The adventitious buds rooted and developed into plantlets
when cultured simply on MS medium. Using this protocol, up to 37,600 plants were
produced from a single leaf explant in one year. From the ethanol extract of the
leaves of this micropropagated plant, 13 compounds were isolated and identified,
including two flavones (1, 11), four flavonols (9, 10, 12, and 13), three
phenylethanoid glycosides (6-8), two alkylated glycosides (2-3), and two steroids
(4-5). Of these, acteoside (7) exhibited anti-tyrosinase activity in human
epidermal melanocytes and luteolin 7-O-beta-D-glucopyranoside (11) exhibited the
greatest neurocytoprotective activity. CONCLUSIONS: The method, indirect shoot
organogenesis from leaf explants of H. pogonocalyx, could be developed to supply
enough quantity of plant materials for the chemical and pharmacological
investigation. In the present study, the isolated active compounds may develop
for whitening agents or treating neurodegenerative diseases in the future.
PMID- 28510889
TI - Comparative analysis among three Taiwan-specific Gentiana species and Chinese
medicinal plant Gentiana scabra.
AB - BACKGROUND: The root of Gentiana scabra is commonly known as Longdan in Chinese
herbal medicines and has been used in the treatment of inflammation, anorexia,
indigestion and gastric infections for over 2000 years. High market demand had
made G. scabra (GS) plants not to be the only source of Longdan in China, other
Gentiana spp., G. triflora, G. manshurica and G. rigescens, were also recognized
as Longdan in China now. RESULTS: In this study, we identified three Taiwan
specific Gentiana spp., G. davidii var. formosana (GDF) and G. arisanensis (GA)
and G. scabrida var. punctulata (GSP) that are phylogenetically different from GS
(main source of Longdan). However, the active compounds of Longdan,
gentiopicroside and swertiamari, were found in GSP and GDF showed higher
antioxidant ability and free radical scavenging activities than Chinese Longdan.
This discovery might explore the medicinal potential of GDF. Meanwhile, another
Taiwan-specific Gentiana spp., GSP, was found to have the strongest antioxidant
ability and free radical scavenging activities which might suggest a possible use
of GSP as a source of natural antioxidant agents for industrial purpose.
CONCLUSIONS: The finding of this study indicated that ITS analysis can be used to
identify Taiwan-specific Gentiana spp. Also the Taiwan-specific Gentiana spp.
which has strongest antioxidant and free radical scavenging activities among
others could be a better choice for industrial purpose.
PMID- 28510891
TI - A new name and seventeen new combinations in the Magnolia (Magnoliaceae) of China
and Vietnam.
AB - BACKGROUND: A new name is proposed and seventeen new combinations are made as a
result of the previous reduction of the remaining genera of subfamily
Magnolioideae (Magnoliaceae) into the genus Magnolia. RESULTS: The replacement
name Magnolia fansipanensis is proposed for Manglietia crassifolia Q. N. Vu et
al., since its transfer to Magnolia would create an illegitimate later homonym of
the fossil name M. crassifolia Gopp. A further 17 new combinations are made to
transfer the following taxa to Magnolia: Manglietia guangzhouensis A. Q. Dong et
al., M. kaifui Q. W. Zeng & X. M. Hu, M. lawii N. H. Xia & W. F. Liao, plus
Michelia concinna H. Jiang & E. D. Liu, M. jianfenglingensis G. A. Fu & K. Pan,
M. viridipetala Y. W. Law et al., M. wuzhishangensis G. A. Fu & K. Pan, M.
xianianhei Q. N. Vu and Yulania carnosa D. L. Fu & D. L. Zhang, Y. cuneatofolia
T. B. Chao (probably Zhao) et al., Y. dabieshanensis T. B. Zhao et al., Y.
dimorpha T. B. Zhao & Z. X. Chen, Y. fragarigynandria T. B. Zhao et al., Y.
shirenshanensis D. L. Fu & T. B. Zhao, Y. shizhenii D. L. Fu & F. W. Li, Y.
verrucata D. L. Fu et al. and Y. xinyangensis T. B. Zhao et al. CONCLUSIONS: The
transfer of the above taxa to Magnolia is necessary following the present almost
universal recognition of Magnolioideae as one of two monogeneric subfamilies
within Magnoliaceae.
PMID- 28510890
TI - Antibacterial, anti-glucosidase, and antioxidant activities of selected highland
ferns of Malaysia.
AB - BACKGROUND: Ferns contain natural products with potential therapeutic
applications. Current knowledge of the pharmacological properties of ferns,
specifically those growing at high altitudes, is limited. This study aimed to
evaluate the phytochemical contents as well as antibacterial, anti-glucosidase,
and antioxidant activities of four highland ferns in Malaysia. RESULTS: Aqueous
extracts of the leaves and rhizomes of Cyathea latebrosa, Dicranopteris curranii,
Gleichenia truncata, and Phymatopteris triloba were analysed. P. triloba leaf
extract had the highest contents of total flavonoids (118.6 mg/g dry matter),
hydroxycinnamic acids (69.7 mg/g dry matter), and proanthocyanidins (29.4 mg/g
dry matter). P. triloba leaf and rhizome extracts as well as G. truncata leaf
extract inhibited the growth of both Gram-positive and Gram-negative bacteria. P.
triloba leaf extract produced a minimum inhibitory concentration (MIC) value of
0.78 mg dry matter/mL when tested against Pseudomonas aeruginosa, which is 2.5
fold higher than that of ampicillin. Among all extracts, P. triloba leaf extract
had the highest anti-glucosidase activity (EC50 = 56 MUg dry matter/mL) and also
the highest antioxidant potential based on DPPH radical scavenging and Ferric
Reducing Antioxidant Power assays. Antioxidant activities of both the leaf and
rhizome extracts correlated positively with total flavonoid and hydroxycinnamic
acid contents (R2 = 0.80-0.95). On the other hand, anti-glucosidase activity
correlated with total proanthocyanidin contents in both the leaf and rhizome
extracts (R2 = 0.62-0.84). CONCLUSIONS: In conclusion, highland ferns are
potential sources of antibacterial agents, glucosidase inhibitors, and
antioxidants.
PMID- 28510892
TI - Sedum tarokoense (Crassulaceae), a new species from a limestone area in Taiwan.
AB - BACKGROUND: An unknown Sedum was found from the limestone region in Taiwan. After
a detailed comparison with other congeners in Taiwan and neighboring countries,
we identified this plant as a new species. RESULTS: This new taxon resembles S.
nokoense Yamamoto, S. alfredii Hance, and S. uniflorum Hook. & Arn. subsp.
oryzifolium (Makino) H. Ohba, but differs in leaf shape, sepal morphology, and
seed testa micro-morphology. Ecologically, this new taxon occurs exclusively on
limestone, while S. nokoense and S. alfredii grow in non-limestone areas and S.
uniflorum subsp. oryzifolium is only found on sandy seashores. CONCLUSIONS: Sedum
tarokoense H.W. Lin & J.C. Wang is described as a new species. We provide a
description, line drawing, and distribution map, as well as photograph, a key and
a table to distinguish S. tarokoense from its related species.
PMID- 28510893
TI - De novo transcriptome assembly and novel microsatellite marker information in
Capsicum annuum varieties Saengryeg 211 and Saengryeg 213.
AB - BACKGROUND: Pepper, Capsicum annuum L., Solanaceae, is a major staple
economically important vegetable crop worldwide. Limited functional genomics
resources and whole genome association studies could be substantially improved
through the application of molecular approach for the characterization of gene
content and identification of molecular markers. The massive parallel
pyrosequencing of two pepper varieties, the highly pungent, Saengryeg 211, and
the non-pungent, Saengryeg 213, including de novo transcriptome assembly,
functional annotation, and in silico discovery of potential molecular markers is
described. We performed 454 GS-FLX Titanium sequencing of polyA-selected and
normalized cDNA libraries generated from a single pool of transcripts obtained
from mature fruits of two pepper varieties. RESULTS: A single 454 pyrosequencing
run generated 361,671 and 274,269 reads totaling 164.49 and 124.60 Mb of sequence
data (average read length of 454 nucleotides), which assembled into 23,821 and
17,813 isotigs and 18,147 and 15,129 singletons for both varieties, respectively.
These reads were organized into 20,352 and 15,781 'isogroups' for both varieties.
Assembled sequences were functionally annotated based on homology to genes in
multiple public databases and assigned with Gene Ontology (GO) terms. Sequence
variants analyses identified a total of 3,766 and 2,431 potential (Simple
Sequence Repeat) SSR motifs for microsatellite analysis for both varieties, where
trinucleotide was the most common repeat unit (84%), followed by di (9.9%), hexa
(4.1%) and pentanucleotide repeats (2.1%). GAA repeat (8.6%) was the most
frequent repeat motif, followed by TGG (7.2%), TTC (6.5%), and CAG (6.2%).
CONCLUSIONS: High-throughput transcriptome assembly, annotation and large scale
of SSR marker discovery has been achieved using next generation sequencing (NGS)
of two pepper varieties. These valuable informations for functional genomics
resource shall help to further improve the pepper breeding efforts with respect
to genetic linkage maps, QTL mapping and marker-assisted trait selection.
PMID- 28510894
TI - Biomass carbon accumulation in aging Japanese cedar plantations in Xitou, central
Taiwan.
AB - BACKGROUND: Japanese cedar (Chrytomeria japonica D. Don) is an important
plantation species in Taiwan and represents 10% of total plantation area. It was
first introduced in 1910 and widely planted in the northern and central
mountainous areas of Taiwan. However, a change in forest management from exotic
species to native species in 1980 had resulted in few new Japanese cedar
plantations being established. Most Japanese cedar plantations are now between 30
and 50 years old and reaching their rotation period. It is of interest to know
whether these plantations could be viable for future carbon sequestration through
the accumulations of stand carbon stocks. Twelve even-aged Japanese cedar stands
along a stand age gradient from 37 to 93 years were selected in Xitou of central
Taiwan. The study aims were to investigate the basic stand characteristics and
biomass carbon stock in current Japanese cedar stands, and determine the
relationships among stand characteristics, tree biomass carbon, and stand age.
RESULTS: Our results indicate that existing Japanese cedar plantations are still
developing and their live tree biomass carbon continues to accumulate. At stands
with a stand age of 90 years, tree density, canopy height, mean diameter at
breast height, basal area, and live tree biomass carbon stocks reach to nearly
430 tree ha-1, 27 m, 48 cm, 82 m2 ha-1 and 300 Mg C ha-1, respectively.
CONCLUSIONS: Therefore, with no harvesting, current Japanese cedar plantations
provide a carbon sink by storing carbon in tree biomass.
PMID- 28510896
TI - Conspecificity of two morphologically distinct calcified red algae from the
northwest Pacific Ocean: Galaxaura pacifica and G. filamentosa (Galaxauraceae,
Rhodophyta).
AB - BACKGROUND: Members of the calcified red algal genus, Galaxaura, are distributed
predominantly in warm temperate, subtropical, and tropical regions worldwide. The
capacity of these algae to form calcified thalli could play a critical role in
the carbon cycle of these ecosystems. Previous studies have suggested that the
reported species diversity of Galaxaura may be exaggerated due to a lack of
knowledge regarding external morphological differences between gametophytic and
tetrasporophytic plants (or among different life stages) of a single species.
RESULTS: To examine this issue, this study collected specimens of two
morphologically distinct Galaxaura from Taiwan and the Philippines. These
specimens were initially identified as two species (G. pacifica Tanaka and G.
filamentosa Chou ex Taylor) based on their morphological features. Our molecular
analyses, however, unexpectedly showed that these two specimens shared 100%
identical rbc L sequences, indicating that they represented a single species
comprising two distinct external morphologies. Furthermore, our extensive
observations and molecular analyses on several specimens from different locations
in southern Taiwan has revealed that these morphological differences could be due
to seasonal variation. CONCLUSIONS: This study proposes that G. "filamentosa"
from the Philippines could represent the remnants of the lower villous part of
older gametophytic plants of G. pacifica after senescence of the upper smooth
part of the thallus. As such we propose that these two previously distinct algal
species from the northwest Pacific Ocean as a single species, G. pacifica. This
study shows that the biodiversity of the calcified red algae Galaxaura could be
overestimated without the assistance of molecular tools. Additionally, this study
provides insights into the biodiversity and unique biology of the calcified red
algae Galaxaura.
PMID- 28510895
TI - Similarity and difference in vegetation structure of three desert shrub
communities under the same temperate climate but with different microhabitats.
AB - BACKGROUND: Community structure and species composition are closely related to
plant diversity and ecosystem stability. To explore the similarity in vegetation
structure of shrub communities under the same temperate climate but with
different microhabitats, 36, 28 and 13 sampling plots in Ephedra distachya,
Seriphidium terrae-albae and Artemisia songarica communities were selected
respectively, during the course of three seasons (early spring, summer, autumn)
in Gurbantunggut Desert, north-western China. The species composition, abundance,
biomass and soil nutrients were investigated. Floristic changes were
characterized by similarity and ordination methods. RESULTS: Two communities, E.
distachya and S. terrae-albae, were similar in terms of soil nutrients but
differed from the A. songarica community. Soil organic matter, nitrogen and
biological soil crusts accounted for the differences of microhabitats. In spring
and summer, more plant families, genera and species were recorded in E. distachya
and S. terrae-albae communities than in the A. songarica community but in each
community, the number of families, genera, species, herbs and life forms showed a
consistent trend summer > spring > autumn. There were significant differences in
absolute biomass among the three communities, but the ratio of dead biomass to
total biomass was consistently 1:4, indicating the constant turnover rate of
plant biomass for nutrient cycling. In each community shrubs accounted for the
most biomass. Herbaceous biomass was negligible but the herbs contributed the
most richness and abundance. CONCLUSIONS: The similarity in response of all three
communities to seasonal changes in vegetation structure and biomass allocation
demonstrate convergence although divergence is demonstrated in soil
characteristics or microhabitats.
PMID- 28510897
TI - Detection and identification of the phytoplasma associated with China ixeris
(Ixeridium chinense) fasciation.
AB - BACKGROUND: Phytoplasmas are always associated with symptoms in host plants such
as stunting of stems, witches'-broom, yellowing of leaves, formation of sterile
deformed flowers, virescence and phyllody. Recently also symptom of fasciation
was reported associated with phytoplasma presence. In the present work, China
ixeris fasciation was observed associated with phytoplasmas in Guanzhong Area,
Shaanxi, China. RESULTS: Phytoplasma-like bodies were observed under transmission
electron microscope in stem tissues of symptomatic samples. The 16S rRNA operon
and tuf genes from phytoplasmas were amplified by PCR assays. Phylogenetic trees
were calculated respectively based on sequences data of these two genes. The
pattern of restriction fragment length polymorphism (RFLP) was generated via
digesting the PCR products of 16S rRNA gene with eight restriction enzymes.
CONCLUSION: The presence of phytoplasma in China ixeris exhibiting fasciation
symptom was confirmed by the results of TEM observation and PCR testing. Based on
sequence data, phylogeny analysis and actual restriction fragment length
polymorphism (RFLP) analysis, the associated phytoplasma was classified as
related to 16SrI-C subgroup. This was the first record of phytoplasmas in China
ixeris.
PMID- 28510898
TI - Genetic diversity in populations of Isatis glauca Aucher ex Boiss. ssp. from
Central Anatolia in Turkey, as revealed by AFLP analysis.
AB - BACKGROUND: Isatidae L. is a complex and systematically difficult genus in
Brassicaceae. The genus displays great morphological polymorphism, which makes
the classification of species and subspecies difficult as it is observed in
Isatis glauca Aucher ex Boiss. The aim of this study is characterization of the
genetic diversity in subspecies of Isatis glauca Aucher ex Boiss. distributed
widely in Central Anatolia, in Turkey by using Amplified Fragment Length
Polymorphism (AFLP) technique. RESULTS: Eight different Eco RI-Mse I primer
combinations produced 805 AFLP loci, 793 (98.5%) of which were polymorphic in 67
accessions representing nine different populations. The data obtained by AFLP was
computed with using GDA (Genetic Data Analysis) and STRUCTURE (version 2.3.3)
software programs for population genetics. The mean proportion of the polymorphic
locus (P), the mean number of alleles (A), the number of unique alleles (U) and
the mean value of gene diversity (He) were 0.59, 1.59, 20, and 0.23 respectively.
The coancestry coefficient (Theta) was 0.24. The optimal number of K was
identified as seven. The principal component analysis (PCA) explained 85.61% of
the total genetic variation. CONCLUSION: Isatis glauca ssp. populations showed a
high level of genetic diversity, and the AFLP analysis revealed that high
polymorphism and differentiated subspecies could be used conveniently for
population genetic studies. The principal coordinate analysis (PCoA) based on the
dissimilarity matrix, the dendrogram drawn with UPGMA method and STRUCTURE
cluster analysis distinguished the accessions successfully. The accessions formed
distinctive population structures for populations AA, AB, E, K, and S.
Populations AG1 and AG2 seemed to have similar genetic content, in addition, in
both populations several hybrid individuals were observed. The accessions did not
formed distinctive population structures for both populations AI and ANP.
Consequently, Ankara province might be the area, where species Isatis glauca
Aucher ex Boiss. originated.
PMID- 28510899
TI - Rapid regeneration and ploidy stability of 'cv IR36' indica rice (Oryza Sativa.
L) confers efficient protocol for in vitro callus organogenesis and Agrobacterium
tumefaciens mediated transformation.
AB - BACKGROUND: Cereal crops are the major targets for transformation mediated crop
improvement and IR36 is an early maturing, high yielding, insect and disease
resistant rice variety however, it is abiotic stress sensitive. Hence,
development of an efficient and reproducible micropropagation system via somatic
embryogenesis and Agrobacterium tumefaciens mediated transformation is
prerequisite to develop abiotic stress tolerant IR36. Further, Genetic stability
of analysis of plantlets through RAPD and ISSR and Ploidy level through Flow
cytometry (FCM) measurement of 2C DNA content is necessary for future application
of transformed IR36. RESULTS: In this study, Mature seeds inoculated on
(Murashige and Skoog) MS medium with 11.31 MUM 2, 4-dichlorophenoxyacetic acid
(2, 4-D) and 0.3 MUM Kinetin (Kn) had highest callus induction frequency (98%).
The highest regeneration frequency (80%) was observed in MS + 13.28 MUM
Benzyladenine (BA) with 8.06 MUM alpha-naphthalene acetic acid (NAA). Randomly
Amplified Polymorphic DNA (RAPD), Inter Simple Sequence Repeat (ISSR) and Flow
Cytometry (FCM) analysis showed no significant variation in the 2C DNA (0.81
pg/2C) content and Ploidy level between wild type IR36 and in vitro maintained
rice lines. Of the various OD bacterial culture, an optimum OD of 0.4 and
inoculation duration of 10 min resulted in efficient Agrobacterium-mediated
transformation. beta-glucuronidase activity was maximum in callus (99.05%).
CONCLUSIONS: These results described here confirm the reliability of this
protocol for micropropagation and delivery of desirable gene using A. tumefaciens
into indica rice.
PMID- 28510900
TI - High frequency microcloning of Aloe vera and their true-to-type conformity by
molecular cytogenetic assessment of two years old field growing regenerated
plants.
AB - BACKGROUND: Aloe vera (L.) Burm.f is an important industrial crop, which has
enormous application in pharmaceutical, cosmetic and food industries. Thereby,
the demand for quality planting material of A. vera is increasing worldwide.
Micropropagation is the widely accepted practical application of plant
biotechnology that has gained the status of a multibillion-dollar industry
throughout the world and this techniques can be used to meet the industrial
demand of A. vera. Present studies aim to develop a proficient methods of high
frequency true-to-type plantlet regeneration without intermediate callus phase
for A. vera. RESULTS: Nodal portion of rhizomatous stem of A. vera were cultured
on Murashige and Skoog (MS) medium (Physiol. Plant. 15:473 - 497, 1962)
supplemented with various cytokinin and A. vera leaf gel (AvG) as organic
supplement. Number of proliferated shoots per explant was increased along with
the regeneration cycles and on MS medium supplemented with 2.5 mg/L 6
benzylaminopurine and 10.0% (v/v) AvG, only 17.8 +/- 0.35 shoots per explant were
induced on 1st regeneration cycle whereas on 3rd regeneration cycle these number
increase to 38.5 +/- 0.44 shoots per explant on the same medium composition. AvG
have an encouraging role to increase the proliferation rate and on 3rd
regeneration cycle 27.6 +/- 0.53 shoot per explant induced on 2.5 mg/L BAP, but
these number increase to 38.5 +/- 0.44 shoots per explant when 10.0% (v/v) AvG
was added along with 2.5 mg/L BAP. After transfer of individual excised shoots to
a one-third strength MS medium containing 20.0% (v/v) AvG, all the shoots formed
whole plantlets with maximum number (9.6 +/- 0.29) of roots per shoot. 95.0% of
the regenerated plantlets survived on poly-green house. Normal flower appeared in
84.2% field growing micropropagated plants after 18 to 20 months of field
transfer. Further, clonal fidelity of the two years old micropropagated plants
was established by studying mitotic and meiotic chromosomal behavior and also
considered the chromosome number and structural organization. There were no
alterations in chromosome phenotypes, somatic haploid (pollen mitosis) and
diploid chromosome count (n = 7; 2n = 14), or meiotic behavior. Randomly
amplified polymorphic DNA analyses revealed there were no somaclonal variations
among these regenerants. CONCLUSIONS: These results confirm the very reliable
method for large scale production of true-to-type plantlets of A. vera, which can
be used for commercial purpose.
PMID- 28510901
TI - Aspidistra crassifila (Asparagaceae), a new species from Guangxi, China.
AB - BACKGROUND: Aspidistra crassifila Yan Liu & C.-I Peng, a new species of the
Asparagaceae from Guangxi Zhuang Autonomous Region, China, is described and
illustrated. RESULTS: The new species is similar to A. subrotata Y. Wan & C. C.
Huang in the perianth lobes triangular-lanceolate and horizontally spreading, but
differs by the perianth campanulate, lobes with appendages at base, stamens 6-8
mm long, filaments enlarged, anthers adnate to perianth tube, connectives
extended and upcurved. The chromosome number of the new species was determined to
be 2n = 38, and the karyotype was formulated as 2n = 22m2SC+4sm+12st. CONCLUSION:
A careful study of the literature, herbarium specimens and living plants, both in
the wild and in cultivation in the experimental greenhouse, support the
recognition of the new species Aspidistra crassifila, which is described herein.
Aspidistra crassifila is currently known only from Shiwandashan Mountains, which
lie in southern Guangxi. A line drawing, color plates and a distribution map are
given for the new species to aid in identification.
PMID- 28510902
TI - In vitro growth and carbon utilization of the green-leaved orchid Dendrobium
officinale are promoted by mycorrhizal associations.
AB - BACKGROUND: Mycorrhizal associations play a key role in the life cycle and
evolutionary history of orchids. All orchids grow from extremely small seeds that
are lacking in reserves, and germination and growth into an underground
heterotrophic, achlorophyllous stage depend upon symbiotic fungi to provide
nutrient. However, the nutritional physiology between this symbiosis and green
leaved orchids is still unclear. To understand further how these associations
affect growth and carbon utilization of green orchids, the green orchids were
inoculated with two symbiotic fungi isolated from the roots of a wild orchid
(Dendrobium officinale) in vitro and 13C stable isotope signature experiments
were designed to analyze carbon nutrition acquisition. RESULTS: After two months,
both fungi had formed mycorrhizal associations with the host roots. Moreover, the
growth rate was more rapid for the mycorrhizal seedlings than for the non
mycorrhizal seedlings. The mycorrhizal seedlings not only absorbed more 13C from
the substrate, but also the S3-mycorrhizal seedlings assimilated more atmospheric
13CO2 due to significantly higher effective quantum yield of photosystem II,
compared with the non-mycorrhizal seedlings. These results suggested that the
green orchids could receive more C nutrition from the substrate due to symbiotic
fungi, and photosynthesis capacity of the green D. officinale could be enhanced
by the S3 fungus, therefore carbon nutrition acquisition also increased. As a
result, the S1- and S3- mycorrhizal seedlings showed markedly higher biomass and
polysaccharides contents than the non-mycorrhizal seedlings. CONCLUSIONS: These
results improve our understanding of the mycorrhizal functioning in the green
Dendrobium and show some potential application in the cultivation of D.
officinale.
PMID- 28510903
TI - Characterization of soil organic matter in perhumid natural cypress forest:
comparison of humification in different particle-size fractions.
AB - BACKGROUND: The Chamaecyparis forest is a valuable natural resource in eastern
Asia. The characteristics of soil humic substances and the influence of
environmental factors in natural Chamaecyparis forests in subtropical mountain
regions are poorly understood. The study site of a perhumid Chamaecyparis forest
is in the Yuanyang Lake Preserved Area in northcentral Taiwan. We collected
samples from organic horizons (Oi, Oe and Oa) and from the surface horizon (O/A
horizon) at the summit, footslope and lakeshore to characterize the composition
of the soil organic matter. Samples of organic horizons were dried and ground,
and those of the O/A horizon were passed through wet sieving for different
particle-size fractions before analysis. The C chemical structure in the samples
was determined with CP/MAS 13C NMR spectra. RESULTS: The ratios of alkyl-C/O
alkyl-C and aromaticity increased with decomposition of litter from the Oi, Oe,
to Oa horizon. The ratio of alkyl-C/O-alkyl-C also increased from coarse (> 250
MUm) to very fine (< 2 MUm) particle fractions, which indicates increased
humification of soil organic matter (SOM) in the fine-sized fractions. However,
aromaticity tended to decrease with decreasing particle size, so it may not be
useful in evaluating SOM humification of different particle-size fractions.
CONCLUSIONS: The humification degree of the samples from O horizons and different
particle-size fractions of the O/A horizon showed no gradient change with change
in topography. This prevalent slow decomposition of organic matter in these
perhumid climate conditions may narrow the difference in humification from the
summit to lakeshore.
PMID- 28510904
TI - Effects of abscisic acid and brassinolide on photosynthetic characteristics of
Leymus chinensis from Songnen Plain grassland in Northeast China.
AB - BACKGROUND: It has been well demonstrated that plant growth regulators have
important functions in multiple physiological processes. ABA and BR play crucial
roles in response of crops to stresses. Photosynthetic capacity of Leymus.
chinensis treated by various concentrations of ABA and BR in combination was
determined. Further more, the mechanisms of ABA and BR treatments and potential
for recovery of saline-alkali grasslands were discussed. RESULTS: Abscisic acid
(ABA) and brassinolide (BR) affected leaf gas exchange, growth and biomass of L.
chinensis. The application of ABA and BR mixtures, especially that of 0.01 mM ABA
and 2 * 10-4 mM BR, increased the net photosynthetic rate, stomatal conductance,
water use efficiency, the maximum net photosynthetic rate, light-saturated rate,
leaf respiration rate, the maximum RUBP carboxylation rate, the maximum electron
transport rate, the maximum triose-phosphate utilization, carboxylation
efficiency and the quantum efficiency of PSII and subsequently enhanced density,
height and biomass in L. chinensis. We also observed reduction in the light
compensation and saturation points following the application of ABA and BR
treatments. CONCLUSIONS: We concluded that proper use of plant growth regulators
can enhance the plant growth and productivity on the Songnen grassland, which is
particularly important for the improvement of saline - alkaline grassland and the
yield of grazing lands.
PMID- 28510906
TI - Phylogenetic analyses of Begonia sect. Coelocentrum and allied limestone species
of China shed light on the evolution of Sino-Vietnamese karst flora.
AB - BACKGROUND: The picturesque limestone karsts across the Sino-Vietnamese border
are renowned biodiversity hotspot, distinguished for extremely high endemism of
calciphilous plants restricted to caves and cave-like microhabitats that have
functioned as biological refugia on the otherwise harsh habitats. To understand
evolutionary mechanisms underlying the splendid limestone flora, dated phylogeny
is reconstructed for Asian Begonia, a species-rich genus on limestone substrates
represented by no less than 60 species in southern China, using DNA sequences of
nrITS and chloroplast rpL16 intron. The sampling includes 94 Begonia species
encompassing most major Asian clades with a special emphasized on Chinese
species. RESULTS: Except for two tuberous deciduous species and a species with
upright stems, a majority of Sino-Vietnamese limestone Begonia (SVLB), including
sect. Coelocentrum (19 species sampled) and five species of sect. Diploclinium,
Leprosae, and Petermannia, are rhizomatous and grouped in a strongly supported
and yet internally poorly resolved clade (Clade SVLB), suggesting a single
evolutionary origin of the adaptation to limestone substrates by rhizomatous
species, subsequent species radiation, and a strong tendency to retain their
ancestral niche. Divergence-time estimates indicate a late Miocene
diversification of Clade SVLB, coinciding with the onset of the East Asian
monsoon and the period of extensive karstification in the area. CONCLUSIONS:
Based on our phylogenetic study, Begonia sect. Coelocentrum is recircumscribed
and expanded to include other members of the Clade SVLB (sect. Diploclinium: B.
cavaleriei, B. pulvinifera, and B. wangii; sect. Leprosae: B. cylindrica and B.
leprosa; sect. Petermannia: B. sinofloribunda). Because species of Clade SVLB
have strong niche conservatism to retain in their ancestral habitats in cave-like
microhabitats and Begonia are generally poor dispersers prone to diversify
allopatrically, we propose that extensive and continuous karstification of the
Sino-Vietnamese limestone region facilitated by the onset of East Asian monsoon
since the late Miocene has been the major driving force for species accumulation
via geographic isolation in Clade SVLB. Morphologically species of Clade SVLB
differ mainly in vegetative traits without apparent adaptive value, suggesting
that limestone Begonia radiation is better characterized as non-adaptive, an
underappreciated speciation mode crucial for rapid species accumulations in
organisms of low vagility and strong niche conservatism.
PMID- 28510907
TI - Sex expression and inbreeding depression in progeny derived from an extraordinary
hermaphrodite of Salix subfragilis.
AB - BACKGROUND: An extraordinary hermaphrodite of dioecious willows provides us an
opportunity to examine the inheritance of sex expression and the magnitude of
inbreeding depression using a progeny assay of the hermaphrodite. RESULTS: We
indentified 165 progeny of an open-pollinated hermaphrodite of Salix subfragilis
as siblings selfed (Self) or crossed with another hermaphrodite (Cross_H) or a
male (Cross_M) using microsatellite genotypes. There were more selfed progeny
(110 in Self) than outcrossed progeny (31 in Cross_H and 24 in Cross_M),
suggesting the absence of barriers to selfing in the maternal hermaphrodite. The
sex ratio (female:male:hermaphrodite) of the progeny differed among the sibling
groups (27:17:66 in Self, 3:16:12 in Cross_H and 9:8:7 in Cross_M). Nearly half
of the selfed progeny were hermaphrodites, suggesting that an identical
combination of parental alleles in progeny reproduced the hermaphroditism of the
parent. We measured fitness components of growth (stem height and basal area),
survival and fertility (pollen germination proportion, number of ovules and seed
set). The magnitudes of inbreeding depression in growth and survival (0.29-0.70)
were higher than those in fertility (0.00-0.16). CONCLUSIONS: The findings
suggest a genetic basis of extraordinary hermaphroditism and substantial
inbreeding depression in survival and growth in the dieocious S. subfragilis.
PMID- 28510905
TI - Zoomed MRI Guided by Combined EEG/MEG Source Analysis: A Multimodal Approach for
Optimizing Presurgical Epilepsy Work-up and its Application in a Multi-focal
Epilepsy Patient Case Study.
AB - In recent years, the use of source analysis based on electroencephalography (EEG)
and magnetoencephalography (MEG) has gained considerable attention in presurgical
epilepsy diagnosis. However, in many cases the source analysis alone is not used
to tailor surgery unless the findings are confirmed by lesions, such as, e.g.,
cortical malformations in MRI. For many patients, the histology of tissue
resected from MRI negative epilepsy shows small lesions, which indicates the need
for more sensitive MR sequences. In this paper, we describe a technique to
maximize the synergy between combined EEG/MEG (EMEG) source analysis and high
resolution MRI. The procedure has three main steps: (1) construction of a
detailed and calibrated finite element head model that considers the variation of
individual skull conductivities and white matter anisotropy, (2) EMEG source
analysis performed on averaged interictal epileptic discharges (IED), (3) high
resolution (0.5 mm) zoomed MR imaging, limited to small areas centered at the
EMEG source locations. The proposed new diagnosis procedure was then applied in a
particularly challenging case of an epilepsy patient: EMEG analysis at the peak
of the IED coincided with a right frontal focal cortical dysplasia (FCD), which
had been detected at standard 1 mm resolution MRI. Of higher interest, zoomed MR
imaging (applying parallel transmission, 'ZOOMit') guided by EMEG at the spike
onset revealed a second, fairly subtle, FCD in the left fronto-central region.
The evaluation revealed that this second FCD, which had not been detectable with
standard 1 mm resolution, was the trigger of the seizures.
PMID- 28510908
TI - Correlation between DNA methylation and chronological age of Moso bamboo
(Phyllostachys heterocycla var. pubescens).
AB - BACKGROUND: Chronological age is the primary consideration when studying the
physiological development, aging, and flowering of bamboo. However, it's
difficult to determine bamboo's chronological age if the time of germination is
unknown. To investigate the chronological age of bamboo from the genomic DNA
methylation profile, methylation-sensitive amplification polymorphism (MSAP) was
employed to analyze the genomic DNA methylation of Moso bamboo (Phyllostachys
heterocycla var. pubescens) from stands of nine germination-ages, using six
primer pairs which have previously been shown to yield methylation rates that
reflect the age of Moso bamboo. RESULTS: The results showed that the total
genomic DNA methylation rates in Moso bamboo at different chronological ages were
significantly different, and the increase in genomic DNA methylation rate was
consistent with the increase of chronological age. Six primer pairs displayed
different genomic DNA methylation rates in Moso bamboo of nine age's group;
however, a significantly positive correlation existed among these primer pairs.
An integrated index was obtained by performing principal component analysis on
the six primer pairs to represent the genomic DNA methylation levels in Moso
bamboo of various chronological ages, and a quadratic curve between the
chronological age and genomic DNA methylation levels was obtained. CONCLUSIONS:
Such a relationship between DNA methylation and its chronological age may serve a
reference for its aging study in Moso bamboo.
PMID- 28510909
TI - Variations in osmotic adjustment and water relations of Sphaerophysa kotschyana:
Glycine betaine, proline and choline accumulation in response to salinity.
AB - BACKGROUND: Sphaerophysa kotschyana Boiss. is naturally distributed in overly
salty regions. The key to the completion of the life cycles of S. kotschyana in
harsh saline soils may be hidden in changes of its osmo-protectants, but there is
currently no information about the interaction between osmotic adjustment and
water relations in adaptation to saline conditions. The aim of this article was
to determine growth, relative growth rate (RGR), relative water content (RWC),
osmotic potential (PsiPi), photosynthetic efficiency (Fv/Fm), thiobarbituric acid
reactive substances (TBARS) and osmo-protectant contents [proline (Pro), choline
(Cho) and glycine betaine (GB)] in S. kotschyana leaves and roots exposed to 0,
150 or 300 mM NaCl for 7 and 14 d (days). RESULTS: The results clearly showed
that the reductions in growth, RWC, Fv/Fm, RGR and PsiPi were more pronounced at
300 mM, especially after 14 d. In the same group, the highest increase in TBARS
was recorded in roots (126%) and leaves (31%). The induction at 150 mM was not as
high. Therefore, roots appear to be the most vulnerable part of this plant.
Moreover, S. kotschyana was able to withstand short-term low salinity.
CONCLUSIONS: The osmo-protectant accumulation in S. kotschyana as a salinity
acclimation or adaptation was sufficient for toleration of low salt concentration
(150 mM). In contrast, the plants exposed to the highest NaCl concentration (300
mM) were not able to maintain the ability to prevent water loss because of
further decrease in root/shoot ratio of fresh weight (FW) and dry weight (DW),
RWC and RGR.
PMID- 28510910
TI - Cloning of a new glutathione peroxidase gene from tea plant (Camellia sinensis)
and expression analysis under biotic and abiotic stresses.
AB - BACKGROUND: Tea plant, Camellia sinensis (L.) O. Kuntze, a well-known heavy metal
hyperaccumulator, possesses a powerful tolerance to heavy metals. The heavy metal
stresses lead to reactive oxygen species (ROS) production, and high concentration
of ROS is harmful to plants. The glutathione peroxidase gene has positive
function to damage induced by ROS. To understand the mechanism of tolerance to
deferent stresses in tea plant, a new glutathione peroxidase gene of tea plant
was cloned and its expression pattern was analyzed under abiotic and biotic
stresses. RESULTS: A novel cDNA encoding glutathione peroxidase of tea plant
(Camellia sinensis) was isolated by rapid amplification of cDNA ends (RACE)
method and designated as CsGPX2 (GenBank Accession No. JQ247186). This full
length sequence was 917 nucleotides including a 510 bp open reading frame (ORF),
which encoded a polypeptide of 169 amino acids. The deduced amino acid sequence
showed high homology with glutathione peroxidases of angiosperms and contained
the characteristic conserved motifs of ILAFPCNQF and FTVKD, the highest level of
similarity was 85% to a glutathione peroxidase from Ricinus communis (Accession
NO. XP_002509790.1). Tissue expression pattern analysis indicated that CsGPX2
expressed similarly in root, stem, leaf and flower of tea plant. The CsGPX2 gene
showed strong responses to most abiotic stresses including salinity, heavy metal
toxicity, drought, heat, plant hormones, but could not be induced by biotic
treatment. CONCLUSIONS: The result suggested that CsGPX2 had potential function
in protecting tea plant from peroxidative damage induced by some abiotic
stresses.
PMID- 28510911
TI - Karyological, morphological and phytochemical characteristics of medicinal plants
Sophora flavescens Aiton grown from seeds collected at different localities.
AB - BACKGROUND: Dried roots of Sophora flavescens Aiton contain many phytochemicals
that exhibit beneficial effects on human health. This study examined and compared
the karyological, morphological and phytochemical characteristics of three S.
flavescens populations collected from the Danda, Hualien and Yuli of Taiwan and a
population collected from Gansu, China. RESULTS: Karyotypes of the four
populations were similar, with a diploid number of 2n = 18. The Hualien
population produced more roots but with less matrine and oxymatrine contents in
its root tissue than others. However, only the root of Danda population had a
measurable level of naringenin. The dried root of Yuli population had greater
ferric reducing antioxidant power and trolox equivalent antioxidant capacity than
that of the other populations. CONCLUSIONS: Thus, the collected S. flavescens
populations, particularly the population collected from Danda, have the potential
to be used in breeding programs.
PMID- 28510912
TI - Endemic Amorphophallus (Araceae) from Madagascar: a revised key, a new species
and molecular phylogeny.
AB - BACKGROUND: Since the revision of Amorphophallus of Madagascar (Bot Jahrb Syst
121(1):1-17, 1999) several additional new species have been described. The recent
discovery of another new species promted the preparation of a revised key as well
as the description of the new species. Amorphophallus hildebrandtii, never
restudied since its analysis by Engler in 1881, has been refound and restudied.
Meanwhile molecular phylogenetic studies have provided new insights in the
relationships of the endemic Madagascan species. RESULTS: The new species
Amorphophallus perrieri is described. A new revised key to the endemic
Amorphophallus species of Madagascar is provided. An emended description of A.
hildebrandtii is provided. A molecular phylogeny of the endemic Madagascan
species of Amorphophallus is provided. CONLUSIONS: The enigmatic character of a
very short spadix in A. hildebrandtii has been confirmed, after it was thought
for many years that it was artificially shorter in the holotype specimen than in
nature. This was suggested by the fact that the spadix of the holotype is broken.
The monophyletic character of the Madagascan endemic species clade remained
unchallenged after analysis including all new species discovered recently, incl.
the new species presented in this paper.
PMID- 28510913
TI - Effects of foliar application of salicylic acid and nitric oxide in alleviating
iron deficiency induced chlorosis of Arachis hypogaea L.
AB - BACKGROUND: The aim of this experiment was to analyze the alleviation mechanism
of exogenous salicylic acid (SA) and sodium nitroprusside (SNP, a nitric oxide
donor) on peanut seedlings under Fe deficiency. The effects of SA and SNP on iron
uptake and availability, ions balance and oxidant damage were studied with foliar
application of exogenous 1.0 mM SA (SA) or 2.5 mM SNP (SNP) or 0.5 mM SA+1.25 mM
SNP [1/2(SA+SNP)] or 1.0 mM SA+2.5 mM SNP (SA+SNP). RESULTS: The results showed
that after 21 days treatment, the peanut seedlings growing under iron deficiency
conditions exhibited leaf interveinal chlorosis, and this iron-deficiency induced
symptom was prevented by foliar application of SA, SNP, 1/2 (SA+SNP), especially
SA+SNP. The increased contents of chlorophyll and active iron, and increased Fe
accumulation in cell organelles were observed in SA+SNP treated young leaves,
suggesting that an improvement of iron availability in plants. Moreover, the
improved nutrient solution pH, increased H+-ATPase activity and increased iron
concentration in roots in SA+SNP treated plants, suggesting that SA+SNP is
effective in modulating iron uptake. Furthermore, the increased calcium (Ca),
magnesium (Mg) and zinc (Zn) concentrations and decreased manganese (Mn) and
copper (Cu) concentrations in the leaves and roots of peanut indicated that
SA+SNP stimulated the maintenance of ions disturbed by Fe deficiency. In
addition, SA+SNP alleviated the increased accumulation of superoxide anion (O2*-)
generation rate and malondialdehyde (MDA), and modulated the antioxidant enzymes.
CONCLUSIONS: These results indicated that the interaction of SA and SNP promoted
Fe uptake, translocation and activation; modulated the balance of mineral
elements; and protected Fe deficiency induced oxidative stress. Therefore, SA and
SNP had synergistic effects in alleviating chlorosis induced by Fe deficiency.
PMID- 28510914
TI - A phylogenetic examination of the primary anthocyanin production pathway of the
Plantae.
AB - BACKGROUND: Anthocyanin pigments aid in reproduction and provide ultraviolet
protection to land plants. We have examined the phylogenetic relationships among
the five primary enzymes responsible for producing anthocyanin pigment in its
three major forms. Dihydroflavonol 4-reductase (DFR), anthocyanidin synthase
(ANS), Flavonoid 3'glucosyltransferase (F3GT), flavonoid 3'hydroxylase (F3'H),
and flavonoid 3'5' hydroxylase (F3'5'H) are responsible for the final steps in
anthocyanin pigment production. RESULTS: We were interested in how conserved the
anthocyanin pathway genes may be among land plants, and evolutionarily how far
back into the plant lineage anthocyanin production may be traced. The DFR, ANS,
F3GT, and F3'H genes date back 450 million years to the first land plants.
Mosses, spike mosses, and ferns express these four products, although there is no
evidence of sequence orthologues for these genes in algae. Additionally, F3'5'H
is not evident in organisms that predated gymnosperms. CONCLUSION: Our findings
support the hypothesis that "blue" anthocyanin pigments did not evolve until 300
350 mya along with the gymnosperms, although the "red" anthocyanin pigments may
be as ancient as the mosses (~450 mya).
PMID- 28510915
TI - Real-time measurement of phloem turgor pressure in Hevea brasiliensis with a
modified cell pressure probe.
AB - BACKGROUND: Although the pressure flow theory is widely accepted for the
transport of photoassimilates in phloem sieve elements, it still requires strong
experimental validation. One reason for that is the lack of a precise method for
measuring the real-time phloem turgor pressure from the sink tissues, especially
in tree trunks. RESULTS: Taking the merits of Hevea brasiliensis, a novel phloem
turgor pressure probe based on the state of the art cell pressure probe was
developed. Our field measurements showed that the phloem turgor pressure probe
can sensitively measure the real-time variation of phloem turgor pressure in H.
brasiliensis but the calculation of phloem turgor pressure with xylem tension,
xylem sap osmotic potential and phloem sap osmotic potential will under-estimate
it. The measured phloem turgor pressure gradient in H. brasiliensis is contrary
to the Munch theory. The phloem turgor pressure of H. brasiliensis varied from 8
12 bar as a consequence of water withdrawal from transpiration. Tapping could
result in a sharp decrease of phloem turgor pressure followed by a recovery from
8-45 min after the tapping. The recovery of phloem turgor pressure after tapping
and its change with xylem sap flow suggest the importance of phloem water
relationship in the phloem turgor pressure regulation. CONCLUSION: The phloem
turgor pressure probe is a reliable technique for measuring the real-time
variation of phloem turgor pressures in H. brasiliensis. The technique could
probably be extended to the accurate measurement of phloem turgor pressure in
other woody plants which is essential to test the Munch theory and to investigate
the phloem water relationship and turgor pressure regulation.
PMID- 28510916
TI - Reproductive biology of Pittosporum dasycaulon Miq., (Family Pittosporaceae) a
rare medicinal tree endemic to Western Ghats.
AB - BACKGROUND: For successful cultivation and conservation of plants a detailed
knowledge of their reproductive biology is required. The reproductive features of
trees are important to determine the diversity patterns and community structure
of tropical forests. The present study on reproductive biology of Pittosporum
dasycaulon, a rare medicinal tree, was conducted in the shola forests of Vaghamon
hills, one of the foot hills of Southern Western Ghats of India from 2008-2011.
RESULTS: The plant flowers profusely during February to April. Inflorescence is a
raceme and the total number of flowers per inflorescence varies from 96-217. The
flowers are comparatively small, hermaphrodite, short pedicellate, complete,
zygomorphic, pentamerous, polypetalous, hypogynous and light cream in colour with
an average length of 1.14 cm. Anthesis started at 08.30 h and the flowers were
completely opened at approximately 09.30 h followed by anther deshiscence at
10.00-11.30 h. The pollen grains were trizonocolpate with 45 +/- 5.6 MUm in size.
Acetocarmine staining showed 66 +/- 6% fertile pollen at the time of anther
dehiscence. The number of pollen grains in an anther is 5246 +/- 845 and per
flower is 26230 +/- 1021. The stigma is wet, non-papillate, capitate and contains
a thin film of exudates under the light microscope. The superior ovary is densely
covered with papillate hairs and containing 3-8 ovules. The important floral
visitors include bees and butterflies. The plant is self-incompatible and an out
crosser. Fruit set under open-pollination was poor (24%) with 58.3% fruits having
seeds inside. There was no fruit set in manually self pollinated flowers while
over 57% of the cross pollinated flowers set fruits. CONCLUSIONS: Our study
presents a detailed account on reproductive biology of this medicinal tree which
may help in the conservation and genetic improvement of this particular taxa.
PMID- 28510917
TI - Biochemical characterization of a functional recombinant aryl-alcohol
dehydrogenase from Taiwanofungus camphorata.
AB - BACKGROUND: Aryl-alcohol dehydrogenases (AADs) have been known to involve in the
metabolism of aromatic compounds. RESULTS: One TcAAD cDNA (GenBank HQ453361)
encoding a putative aryl-alcohol dehydrogenase (AAD) was cloned from
Taiwanofungus camphorata. The deduced amino acid sequence is conserved among the
reported AADs. A 3-D structural model of the TcAAD has been created based on the
known structure of voltage-dependent potassium channels subunit beta-2 (PDB code:
3EAU). To characterize the TcAAD, the coding region was subcloned into an
expression vector and transformed into Saccharomyces cerevisiae. The recombinant
His6-tagged TcAAD was overexpressed and purified by Ni affinity chromatography.
The purified enzyme showed a band of approximately 39 kDa on a 12% SDS-PAGE. The
molecular mass determined by MALDI-TOF is 40.58 kDa which suggests that the
purified enzyme is a monomeric enzyme. Using veratraldehyde as a substrate, the
KM, Vmax of TcADD was determined at pH 6.0. Using benzyl alcohol derivatives as
substrates, the oxidizing power of TcADD via NAD+ at pH 9.6 was studied.
CONCLUSIONS: The coding sequence of the TcAAD cDNA was introduced into an S.
cerevisiae expression system and the active enzyme purified and characterized.
Understanding the properties of this TcAAD will be beneficial for its potential
in xenobiotic detoxification or production of natural flavors.
PMID- 28510918
TI - Involvement of trehalose in hydrogen sulfide donor sodium hydrosulfide-induced
the acquisition of heat tolerance in maize (Zea mays L.) seedlings.
AB - BACKGROUND: Trehalose, a non-reducing disaccharide, which involves in the
acquisition of various stress tolerance, while hydrogen sulfide (H2S) is
considered as a cell signal molecule, but H2S-induced heat tolerance and
involvement of trehalose in plants is still unclear. RESULTS: In present study,
pretreatment with hydrogen sulfide donor sodium hydrosulfide (NaHS) markedly
increased the accumulation of endogenous H2S in maize seedlings under normal
culture conditions, which in turn improved survival percentage of maize seedlings
and mitigated increase in electrolyte leakage and malonaldehyde (MDA)
accumulation under heat stress. In addition, treatment with NaHS activated
increase in the activity of trehalose-6-phosphate phosphatase (TPP) under normal
culture conditions, followed by induced the accumulation of endogenous trehalose,
but this accumulation was eliminated by addition of sodium citrate, an inhibitor
of TPP. During the process of heat stress, maize seedlings treated with NaHS
maintained higher TPP activity and trehalose content than those of control. On
the other hand, exogenous application of trehalose also increased the content of
endogenous trehalose in maize seedlings under normal culture conditions,
alleviated increase in electrolyte leakage and MDA accumulation under heat
stress, which in turn improved survival percentage of maize seedlings, and the
heat tolerance induced by trehalose was enhanced by exogenous supplement of NaHS,
but exogenous trehalose treatment had not significant effect on the accumulation
of endogenous hydrogen sulfide in maize seedlings. CONCLUSION: These data suggest
that sodium hydrosulfide pretreatment could improve heat tolerance of maize
seedlings and this improvement may be involved in trehalose accumulation by
activating TPP activity.
PMID- 28510919
TI - Eliminating interference by anthocyanin in chlorophyll estimation of sweet potato
(Ipomoea batatas L.) leaves.
AB - BACKGROUND: Spectral reflectance was evaluated for its usefulness as a
nondestructive estimation of chlorophyll (Chl) content from three cultivars of
sweet potato (Ipomoea batatas L.) with green, yellow, and purple leaves grown in
a greenhouse for 22 days. While the green and yellow leaves contain variant
amount of photosynthetic pigments without or with little level of anthocyanins,
the purple leaves, except large amount of photosynthetic pigments, have high
quantity of anthocyanins. RESULTS: For green and yellow leaves, the reciprocal
reflectance (R-1) and derived indices incorporating near infrared (NIR)
reflectance, [(Rlambda)-1 - (RNIR)-1] and [(RNIR/Rlambda) - 1], in the green and
red edge spectral ranges were shown to be strongly correlated (r2 = 0.8 ~ 0.9)
with the chlorophyll content. The root mean square error (RMSE) of the
chlorophyll content estimation using these indices was < 50 mg m-2. However, when
purple leaves containing high levels of anthocyanins were included in the sample,
R-1 in the green spectral range and the above-mentioned indices displayed much
weaker correlations with the chlorophyll content. The RMSE of chlorophyll
estimation using these indices in the green spectral range sharply increased to >
110 mg m-2 when the sample included purple leaves. The new index, [1 -
(Rlambda/RNIR)], was therefore inferred and developed to eliminate the distorting
effect of anthocyanins on chlorophyll content estimation using reflectance in the
green spectral range. For leaves with high levels of anthocyanins, the
correlation between [1 - (Rlambda/RNIR)] and the chlorophyll content remained
strong (r2 = 0.8 ~ 0.9) in the green spectral range, and the RMSE was minimal.
CONCLUSION: The reflectance index, [1 - (Rlambda/RNIR)], therefore represents a
new and useful parameter for estimating leaf chlorophyll content in leaves with
any level of anthocyanins such as purple rice leaf.
PMID- 28510921
TI - Begonia wuzhishanensis (sect. Diploclinium, Begoniaceae), a new species from
Hainan Island, China.
AB - BACKGROUND: Hainan is the largest island of the Indo-Burma Biodiversity Hotspot
and has the best preserved and most extensive tropical forests in China. A recent
study on distribution of endangered species in China identifies southern Hainan
as one of eight hotspots for plant conservation in the country. In continuation
of our studies of Asian Begonia, we report the discovery of an attractive
undescribed species, B. wuzhishanensis C.-I Peng, X.H. Jin & S.M. Ku, from Hainan
Island. RESULTS: Living plant of the new species, Begonia wuzhishanensis, was
collected in 2009 and cultivated in the experimental greenhouse for morphological
and cytological studies. It flowered consecutively in 2012 and 2013 in the
experimental greenhouse, Academia Sinica. It was assigned to the large,
heterogeneous sect. Diploclinium. The chromosome number of this new species was
determined to be 2n = 26. CONCLUSIONS: A careful study of literature, herbarium
specimens and living plants, both in the wild and in cultivation, support the
recognition of the new species Begonia wuzhishanensis, which is described in this
paper. Begonia wuzhishanensis is currently known only from Fanyang, Wuzhishan
Mountain in the center of the island. A line drawing, color plate, and a
distribution map are provided to aid in identification.
PMID- 28510920
TI - Folium Sennae protects against hydroxyl radical-induced DNA damage via
antioxidant mechanism: an in vitro study.
AB - BACKGROUND: In the study, Folium Sennae (FS) was firstly extracted by various
solvents to obtain five FS extracts. Then, five FS extracts were evaluated for
the protective effects against *OH-induced DNA damage, antioxidant abilities in
vitro, and chemical contents using various methods. On this basis, the
correlation graphs between the pharmacological effects and chemical contents were
plotted to obtain the correlation coefficients (R values). Finally, in order to
obtain biological evidence, ethyl acetate extract of FS (EAFS) was investigated
for the protective effect against *OH-induced MSCs (mesenchymal stem cells)
damage using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl) assay. RESULTS: The
pharmacological assays indicated that five FS extracts could effectively protect
against *OH-induced DNA damage. The correlation analysis suggested that the
average R values of total phenolics, total anthraquinones, aloe-emodin, rhein,
and emodin were respectively 0.843, 0.833, 0.753, 0.820, and 0.784, while those
of total sugars and total saponins were respectively 0.103 and 0.0068. The
mechanistic analysis revealed that five FS extracts could also scavenge *OH, *O2
, DPPH* & ABTS*+ radicals, and reduce Cu2+ to Cu+. MTT assay revealed that the
viability of MSCs which were treated with *OH radicals has been effectively
protected by EAFS (3 and 30 MUg/mL). CONCLUSION: On this basis, it can be
concluded that: (i) Folium Sennae exhibits a protective effect against *OH
induced damages to DNA and MSCs; (ii ) The effects may be attributed to
phytophenols (especially aloe-emodin, rhein, and emodin), not sugars or saponins;
(iii) They exert the protective action via hydrogen atom transfer (HAT) and/or
sequential electron proton transfer (SEPT) mechanisms which make phenolic -OH
moiety be oxidized to stable semi-quinone form; (iv) The stability of semi
quinone form can ultimately be responsible for the protective or antioxidant
effect of phytophenols.
PMID- 28510922
TI - Adaptation and interaction of saxicolous crustose lichens with metals.
AB - One of the most successful mechanisms enabling fungi to survive in extreme
subaerial environments is by formation of mutualistic symbioses with algae and/or
cyanobacteria as lichens. Collections, field and mineral weathering studies and
developments in modern instrumental and analytical techniques have considerably
advanced knowledge in understanding tolerance mechanisms to stress, environmental
adaptation, species concepts and evolutionary processes in lichens colonising
metalliferous habitats. This review focuses on the predominantly saxicolous,
crustose, taxonomically notoriously challenging Acarospora sens. lat. Pioneering
studies investigating element and substance localization in Acarospora sens. lat.
in different geological terrains led to the discovery of novel fixation
mechanisms, new minerals and substances associated with lichens, and new taxa and
evolutionary lineages. Acarospora sens. lat. are generally under-represented in
collections. Systematic sampling of Acarospora sens. lat. and other saxicolous
lichens, in different mineralogical environments is now required, a priority
being those occurring in extreme habitats at risk from climatic and other
environmental changes. The potential for the discovery of new lichen and mineral
species associated with Acarospora and other saxicolous crustose lichens, is
high. These may represent special mechanisms to tolerate metal toxicity and other
forms of environmental stress, including photoprotection.
PMID- 28510923
TI - Development of STS and CAPS markers for variety identification and genetic
diversity analysis of tea germplasm in Taiwan.
AB - BACKGROUND: Tea (Camellia sinensis) is an important economic crop in Taiwan.
Particularly, two major commercial types of tea (Paochong tea and Oolong tea)
which are produced in Taiwan are famous around the world, and they must be
manufactured with specific cultivars. Nevertheless, many elite cultivars have
been illegally introduced to foreign countries. Because of the lower cost, large
amount of "Taiwan-type tea" are produced and imported to Taiwan, causing a
dramatic damage in the tea industry. It is very urgent to develop the stable,
fast and reliable DNA markers for fingerprinting tea cultivars in Taiwan and
protecting intellectual property rights for breeders. Furthermore, genetic
diversity and phylogenetic relationship evaluations of tea germplasm in Taiwan
are imperative for parental selection in the cross-breeding program and avoidance
of genetic vulnerability. RESULTS: Two STS and 37 CAPS markers derived from
cytoplasmic genome and ESTs of tea have been developed in this study providing a
useful tool for distinguishing all investigated germplasm. For identifying 12
prevailing tea cultivars in Taiwan, five core markers, including each one of
mitochondria and chloroplast, and three nuclear markers, were developed. Based on
principal coordinate analysis and cluster analysis, 55 tea germplasm in Taiwan
were divided into three groups: sinensis type (C. sinensis var. sinensis),
assamica type (C. sinensis var. assamica) and Taiwan wild species (C.
formosensis). The result of genetic diversity analysis revealed that both
sinensis (0.44) and assamica (0.41) types had higher genetic diversity than wild
species (0.25). The close genetic distance between the first (Chin-Shin-Oolong)
and the third (Shy-Jih-Chuen) prevailing cultivars was found, and many recently
released varieties are the descents of Chin-Shin-Oolong. This implies the
potential risk of genetic vulnerability for tea cultivation in Taiwan.
CONCLUSIONS: We have successfully developed a tool for tea germplasm
discrimination and genetic diversity analysis, as well as a set of core markers
for effective identification of prevailing cultivars in Taiwan. According to the
results of phylogenetic analysis on prevailing tea cultivars, it is necessary to
broaden genetic diversity from wild species or plant introduction in future
breeding programs.
PMID- 28510924
TI - Establishment of hairy root lines and analysis of iridoids and secoiridoids in
the medicinal plant Gentiana scabra.
AB - BACKGROUND: Gentiana scabra is commonly known as 'Longdan' is an important herb
in traditional Chinese medicines, commonly used for the treatment of
inflammation, anorexia, indigestion and gastric infections. Iridoids and
secoiridoids are main bioactive compounds which attributed to the pharmacological
properties of this plant. The use of hairy root cultures as an excellent
alternative for the production of pharmaceutically important metabolites in less
time period with ensured quality of raw materials. RESULTS: An efficient hairy
root culture system of Gentiana scabra and influence of different plant growth
regulators (PGRs) on the production of gentiopicroside, swertiamarin and loganic
acid constituents were described. Leaf explants were infected with Agrobacterium
rhizogenes, which induced hairy roots up to 21%. The transformed hairy root lines
were confirmed by PCR using rolB and rolC gene-specific primers. Among various
solid and liquid media, B5 liquid medium resulted maximum root biomass (36- fold
higher) in 4-weeks. Quantitative analysis showed loganic acid was 6.6- fold
higher in the presence of zeatin (1 mg/l) and gentiopicroside accumulation was
1.8- fold higher in the presence of naphthaleneacetic acid (NAA, 1 mg/l), as
compared to the roots of plants grown in greenhouse. On the other hand, 1.4- and
2.5- fold higher gentiopicroside and swertiamarin were observed in the presence
of 1.0 mg/l NAA as compared to commercial Gentiana herb No. 2. The result also
showed iridoid and secoiridoid contents affected greatly by age, physiology and
growing environment of the plant. CONCLUSIONS: The use of hairy root cultures is
an excellent alternative to harvesting natural or in vitro grown plants to
produce pharmaceutically important metabolites in less time with ensured quality.
PMID- 28510925
TI - CsPI from the perianthless early-diverging Chloranthus spicatus show function on
petal development in Arabidopsis thaliana.
AB - BACKGROUND: In the floral ABC model, B-class genes comprised of DEFICIENS
(DEF)/APETALA3 (AP3) and GLOBOSA (GLO)/PISTILLATA (PI) had been proposed to
involve in second and third whorl floral organ development. However, less is
known about the function of B-class genes from early-diverging angiosperms.
Chloranthaceae is one of the early-diverging angiosperm families. In this study,
we characterized the role of the PI-like gene CsPI cloned from Chloranthus
spicatus which have the simplest perianthless bisexual flowers. RESULTS: The
expression profile analysis reveals high levels of CsPI mRNA in stamens in
Chloranthus spicatus, with weak distribution in leaves and other floral organs.
Nevertheless, CsPI rescued both stamen and petal development in Arabidopsis
thaliana pi-1 mutants and caused partially conversion of sepals into petaloid
organs in wild-type Arabidopsis thaliana plants. Yeast two-hybrid analysis showed
that CsPI can form not only homodimers but also heterodimers with proteins
encoded by Arabidopsis thaliana and Chloranthus spicatus AP3-like genes.
CONCLUSIONS: These results suggested that CsPI has an ancestral function on
stamen development and that CsPI has capability to specify petal development in
Arabidopsis thaliana. The finding indicates that the activity of the encoded PI
like proteins is highly conserved between the early-diverging Chloranthus and
Arabidopsis. Moreover, our results appear to suggest that B-function genes may
not play a role in perianth development in Chloranthus spicatus.
PMID- 28510926
TI - Sarocladium spinificis, a new endophytic species from the coastal grass Spinifex
littoreus in Taiwan.
AB - BACKGROUND: Sarocladium species are frequently associated with grasses as
saprobes, parasites, and mutualistic endophytes. A species of Sarocladium
(anamorphic Hypocreales) was isolated as endophytic fungus from the coastal grass
Spinifex littoreus (Poaceae). RESULTS: According to characterization by LSU and
ITS rDNA sequences and culture morphology and micromorphology, the species
differed from the species hitherto described in Sarocladium. A key to the known
species of Sarocladium is given. CONCLUSIONS: Sarocladium spinificis is proposed
as a new species. LSU rDNA sequences and conidiophore branching and conidium size
are useful characters for distinguishing between species of Sarocladium.
PMID- 28510928
TI - Begonia wui-senioris (sect. Platycentrum, Begoniaceae), a new species from
Myanmar.
AB - BACKGROUND: The flora of Myanmar is under-collected compared with all other
tropical Asian countries. An unknown Begonia was grown from seeds collected from
a limestone hill in Central Myanmar, and compared with potentially allied
species. RESULTS: The unknown Begonia is rhizomatous, has peltate leaves, 2
locular ovaries, and is evergreen. It is clearly assignable to sect.
Platycentrum. Only two other species of Begonia, B. josephii and B.
subperfoliata, in Myanmar have peltate leaves, but they are deciduous tuberous
plants with 3-locular ovaries and belong to sect. Diploclinium. CONCLUSIONS:
Thorough studies of literature and herbarium materials support the recognition of
a new species, Begonia wui-senioris, which is fully described and illustrated.
Begonia wui-senioris has the lowest chromosome number (2n = 14) for the genus.
PMID- 28510927
TI - Overproduction of valuable methoxylated flavones in induced tetraploid plants of
Dracocephalum kotschyi Boiss.
AB - BACKGROUND: Ploidy manipulation is considered an efficient method to increase
production potential of medicinally important compounds. Dracocephalum kotschyi
Boiss. is an endangered medicinal plant of Iran. Various concentrations of
colchicine (0.05, 0.10, 0.20, and 0.50% w/v) were applied to shoot apical
meristems of D. kotschyi seedlings in two and four-leaf stages to induce
tetraploidy. RESULTS: According to the results, 0.5% (w/v) of colchicine can be
effective for polyploidy induction in D. kotschyi. Putative tetraploids were
selected by morphological and microscopic characteristics and their ploidy level
was confirmed by flow cytometry analysis and chromosome counting. The chromosome
number of original diploid plant was confirmed to be 2n = 2* = 20 whereas that of
the tetraploid plant was 2n = 4* = 40. Tetraploid and mixoploid plants showed
different morphological, physiological and microscopic characteristics from those
of diploid counterparts. The total content of flavonoids was increased from
1583.28 in diploids to 1890.07 (MUg/g DW) in stable tetraploids. CONCLUSION: High
Performance Liquid Chromatography with Diode-Array Detection (HPLC-DAD) confirmed
over accumulation of methoxylated hydroxyflavones in solid tetraploid plants of
D. kotschyi.
PMID- 28510929
TI - Production and identification of haploid dwarf male sterile wheat plants induced
by corn inducer.
AB - BACKGROUND: Using the cross of wheat and maize is a very useful way to produce
wheat haploid plants by chromosome elimination. Dwarf male sterile wheat (DMSW)
and corn inducer are potential important germplasm for wheat breeding by
recurrent selection and doubled haploid strategies. There is no report yet to
achieve the haploid plants from DMSW induced by maize inbred line and especially
the corn inducer. RESULTS: Haploid plants of DMSW were successfully obtained in
this study induced by both maize pollens of inducer line and normal inbred line.
The efficiencies for wheat embryos formation and plantlets production induced by
the two corn lines had no significant difference. All the eleven haploid wheat
plants derived from the male sterile material were identified by botanic
appearance, cytology, cytogenetics, and molecular markers. They were all haploid
based on their guard cell length of 42.78-42.90 MUm compared with the diploid
control of 71.52 MUm, and their chromosome number of 21 compared with the diploid
control of 42. In addition, according to anthers, plant height, and molecular
markers, the haploid plants were divided into two types. Eight of them showed
dwarf, having no anthers, and the special band of Rht10, and the other three
plants displayed normal plant height, having anthers, and not containing the
special band of Rht10, indicating that they were originated from the MS2/Rht10
and ms2/rht10 female gametes, respectively. CONCLUSIONS: MS2/Rht10 haploid plants
were successfully obtained in this study by using corn inducer and inbred line,
and will be employed as candidate materials for the potential cloning of MS2
dominant male gene.
PMID- 28510930
TI - Functional characterization of the N-terminal and C-terminal domains of a sesame
group II phytocystatin.
AB - BACKGROUND: Phytocystatins are natural inhibitors of cysteine protease, and may
regulate endo- or exo-genous proteolytic activities in plants. They are
classified into Group I and II differing by the presence of C-terminal extension
of Group II. A cDNA fragment encoding a Group II phytosystatin, SiCYS was
previously obtained from sesame seeds. RESULTS: SiCYS as well as its two
structural domains, N-terminal and C-terminal domains (SiCYS-N and SiCYS-C), was
expressed in Escherichia coli. The recombinant SiCYS and SiCYS-N showed
inhibitory activity against papain. The K i values of SiCYS and SiCYS-N were ~1.9
*10-8 M and ~7.9 *10-8 M, respectively. All the three recombinants possessed
comparable ability to inhibit spore germination of Trichoderma reesei,
Aspergillus sydowii, and Helminthosporium sesamum. Similar protein profile
including proteases in germinating seeds was found in proteins purified by the
SiCYS, SiCYS-N or SiCYS-C coupling affinity column. CONCLUSION: SiCYS exhibited
more effective papain-inhibitory activity than SiCYS-N; while SiCYS-C had almost
no inhibitory activity. All displayed similar antifungal activities indicating
that there is no correlation between antifungal and papain-inhibitory activities.
Structural and sequence analyses suggest that the C-terminal domain of SiCYS may
be originated from gene duplication to enhance its inhibitory activity.
PMID- 28510931
TI - Application of an inducible transposon with anther culture in generation of di
haploid homologous mutants.
AB - BACKGROUND: Insertional mutagenesis represents one of the most effective ways to
acquire information about a plant gene's function. However, it is hindered by the
autosomal genome being diploid and therefore, most mutations being recessive. The
problem is addressed by inducing the transposition during anther culture so that
selected mutations can be transmitted and then regenerated to a homozygous state.
RESULTS: To this end, we treated transgenic rice floral tissues containing the
inducible transposon with an inducer, salicylic acid. Excision events were
detected in regenerated calli and subsequent plantlets. DNA blot and PCR assay
were used to determine the homogeneity of knockout mutants. About 5% of the
mutants containing transposition events were homozygous. Furthermore, the
inducible transposon was active during calli regeneration. CONCLUSIONS: This
strategy could be applicable to improve transposition efficiency in microspore
development stages to create stable di-haploid mutants in plants.
PMID- 28510932
TI - Comparison of leaf anatomy and essential oils from Drimys brasiliensis Miers in a
montane cloud forest in Itamonte, MG, Brazil.
AB - BACKGROUND: Drimys brasiliensis Miers is native to Brazil, where it is mainly
found in montane forests and flooded areas in the South and Southeast regions of
the country. The objectives of the present study were to compare the leaf anatomy
and the chemical constitution of the essential oils from D. brasiliensis present
in two altitude levels (1900 and 2100 m), in a Montane Cloud Forest, in Itamonte,
MG, Brazil. RESULTS: A higher number of sclereids was observed in the mesophyll
of the leaves at 1900 m altitude. At 2100 m, the formation of papillae was
observed on the abaxial surface of the leaves, as well as an increase in the
stomatal density and index, a reduction in leaf tissue thickness, an increase in
the abundance of intercellular spaces in the mesophyll and an increase in
stomatal conductance and in carbon accumulation in the leaves. Fifty-nine
constituents have been identified in the oils, with the predominance of
sesquiterpenes. Two trends could be inferred for the species in relation to its
secondary metabolism and the altitude. The biosyntheses of sesquiterpene alcohols
at 1900 m, and phenylpropanoids and epi-cyclocolorenone at 2100 m, were favored.
CONCLUSIONS: D. brasiliensis presented a high phenotypic plasticity at the
altitude levels studied. In relation to its leaf anatomy, the species showed
adaptive characteristics, which can maximize the absorption of CO2 at 2100 m
altitude, where a reduction in the partial pressure of this atmospheric gas
occurs. Its essential oils presented promising compounds for the future
evaluation of biological potentialities.
PMID- 28510933
TI - Histological characterization of the lateral root primordium development in rice.
AB - BACKGROUND: Lateral root constitutes an important part of root system either in
tap root plants or fibrous root plants. The development of lateral root
primordium (LRP) in Arabidopsis, which has a tap root system with simple radial
structure of primary root, has been well characterized. However, limited
knowledge has been acquired on the plants with fibrous root system, such as rice.
This is mainly due to their multiple cell layers coated on root, which disturb
the observation of LRP. RESULTS: We used an easy and quick method to strip the
epidermal and cortex tissues of primary root so that the LRP can be easily
observed under microscope. In this way, we observed the developmental processes
of LRP in rice. In addition, we described the expression dynamics of several root
development related genes, especially OsPINs (PIN-FORWMED), during the process of
LRP development. CONCLUSIONS: We reported an easy and quick method for LRP
observation in rice and suggested a "fountain" model of auxin transport in LRP of
rice, which is similar with that in Arabidopsis.
PMID- 28510934
TI - The effects of the current and past meteorological elements influencing the
current pollen concentrations for different taxa.
AB - BACKGROUND: It is an important issue to separate the current and past components
of the meteorological parameters influencing the current pollen concentration for
different taxa. For this purpose a new statistical procedure, factor analysis
with special transformation is introduced. The data set used covers an 11-year
period (1997-2007) including daily pollen counts of 19 taxa and 4 climate
variables (mean temperature, precipitation amount, global solar flux and relative
humidity). RESULT: The taxa examined can be classified into three groups, namely
arboreal deciduous (AD), arboreal evergreen (AE) and herbaceous (H) taxa. It was
found that a better comparison can be established if the taxa are separated
within each group according to the starting month of their pollen season. Within
the group of AD taxa, Alnus, Populus and Ulmus are marked by a late summer -
early autumn peak of the role of past meteorological elements exceeding the role
of the current ones almost all over the pollen-free period. For Juglans, Morus,
Platanus and Quercus, the major weights of the current meteorological elements in
the spring and early summer show the most characteristic contribution to the
pollen production. For AE taxa, the picture is no clear. For H taxa, the curves
of Cannabis, Plantago, Rumex and Urtica indicate the most equalized course of
weights. Ambrosia, Artemisia and Chenopodiaceae comprise the highest weights of
the past weather conditions of all taxa until at least three months before the
start of the pollination. Interactions between the phyto-physiological processes
and the meteorological elements are evaluated. CONCLUSION: Separation of the
weight of the current and past weather conditions for different taxa involves
practical importance both for health care and agricultural production.
PMID- 28510935
TI - Effect of short-term water deficit stress on antioxidative systems in cucumber
seedling roots.
AB - BACKGROUND: Cucumber is one of the most popular vegetables, and have little
tolerance for water stress. The antioxidant defense system is one of major
drought defense and adaptive mechanisms in plants, however, relatively few data
are available regarding antioxidant systems in responses of cucumber to water
deficit. The effect of short-term drought stress on the antioxidant system, lipid
peroxidation and water content in cucumber seedlings roots was investigated.
RESULTS: The results showed that polyethylene glycol (PEG) induced water stress
markedly decreased water content of cucumber seedling roots after treatment of 36
h, and caused excessive generation of reactive oxygen species (ROS) including
superoxide (O2.-), hydrogen peroxide (H2O2). Meanwhile, malondialdehyde (MDA)
content increased. Antioxidant enzymes including superoxide dismutases (SOD),
peroxidases (POD), catalase (CAT) and ascorbate peroxidase (APX) activities
increased in different time and different extent under water stress, while
ascorbate (AsA) and glutathione (GSH) content, glutathione reductase (GR),
dehydroascorbate reductase (DHAR) and monodehydroascorbate reductase (MDHAR)
activities all decreased when compared to control. CONCLUSIONS: Therefore, it can
be concluded that water stress strongly disrupted the normal metabolism of roots
and restrained water absorption, and seemingly enzymatic system played more
important roles in protecting cucumber seedling roots against oxidative damage
than non-enzymatic system in short-term water deficit stress.
PMID- 28510936
TI - Effects of copper on leaf membrane structure and root activity of maize seedling.
AB - BACKGROUND: Copper is an important heavy metal pollutant, with strong toxicity
and great harm, which is easy to accumulate in the plant body and is difficult
for degradation. This paper adopts medium culture method, taking "Zheng Dan 958"
maize seedlings as sample materials. With different copper ion concentration
gradients for the simulation of metal copper stress on maize seedlings, it
explored the effects on the membrane structure (POD activity, MDA content,
membrane permeability) and root activity. RESULTS: POD activity increases
dramatically when the copper concentration is over 10 MUmol/L. MDA content
increases sharply when the copper concentration is over 1000 MUmol/L, showing a
rising trend. Membrane permeability increases greatly when the copper
concentration is over 100 MUmol/L. Root activity decreases significantly when the
copper concentration is 100 MUmol/L, showing a clear downward trend. CONCLUSIONS:
The copper concentration of 1000 MUmol/L has exceeded the maize seedling
tolerance to copper, and the activities of protective enzymes of maize seedlings
are inhibited. Cell membrane lipid peroxidation has caused serious damage on the
structure and function of membrane. Structure of root cells of maize seedling is
also damaged, reducing the root activity, so the maize is irreversible hurt.
PMID- 28510937
TI - The seed development of a mycoheterotrophic orchid, Cyrtosia javanica Blume.
AB - BACKGROUND: Cyrtosia javanica is a rare, mycoheterotrophic vanilloid orchid
native to the bamboo forest in central Taiwan. Like some vanilloid orchids, the
seeds of C. javanica are hard and difficult to germinate in vitro. A better
understanding of the embryology would provide insights in the propagation and
conservation of this rare species. RESULTS: Based on the histological and
histochemical studies, we observed some remarkable features in developing seeds
of C. javanica. First, the developing embryos without a structurally defined
suspensor; Second, the chalazal accessory cells have densely stained cytoplasms
that are different from the adjacent cells of seed coat; Third, the multiple
layers of seed coat with the lignified in the outermost cell layer of the outer
seed coat. CONCLUSIONS: In C. javanica, the large and heavy seeds embedded in
fresh fruits may adapt to the dispersal strategy. The hard seeds with lignified
outer seed coat could provide a rigid protection during seed dispersal but also
cause coat-imposed dormancy. This study provides insights in the seed coat
structure and the hints of seed treatment methods.
PMID- 28510938
TI - Fatty acid, tocopherol and squalene contents of Rosaceae seed oils.
AB - BACKGROUND: The aim of current study is to establish the composition of these
seeds belong to Rosaceae family with respect to fatty acid, tocopherol and
squalene content. RESULTS: The oil contents of seeds varied between 3.49
(Cotoneaster bullatus) to 46.15 g/100 g (Prunus tenella). The main fatty acids of
seed oils were oleic (6.50 - 67.11 %), linoleic (22.08 - 68.62 %) and 20:1n-7
(0.10 - 61.59 %). As observed, the oils of seed were rich in linoleic and oleic
acids. Total tocopherol contents ranged between 7.06 mg/100 g (Prunus tenella) to
165.74 mg/100 g (Potentilla glandulosa ssp. pseudorupestris). The major
tocopherols were gamma-tocopherol, ranging from 2.08 mg/100 g to 106.01 mg/100 g;
alpha-tocopherol ranging from 2.86 mg100 g to 74.26 mg/100 g and delta-tocopherol
ranging used in this experiment were found between 0.02 mg/100 g (Alchemilla
caucasica) to o.29 mg/100 g (Cotoneaster simonsii). CONCLUSIONS: These results
show that Rosaceae seed oils can be a potential saurce of valuable oil which
might be useful for the evaluation of dietary information in important food crops
and other industrial applications.
PMID- 28510939
TI - A new Haniffia species (Zingiberaceae) and a new generic record from Sarawak,
Malaysian Borneo.
AB - BACKGROUND: Haniffia Holttum is a genus of three described species of terrestrial
gingers hitherto restricted to Peninsular Thailand and various localities in
Peninsular Malaysia. RESULTS: With generic placement confirmed using nrITS, trn K
and mat K plastid sequence data, Haniffia santubongensis S.Y. Wong & P.C. Boyce
is described as a taxonomically novel species representing a new generic record
for Borneo, to where it is endemic to Mount Santubong, Kuching Division, NW
Sarawak, Malaysian Borneo. An identification key to all species is given and H.
santubongensis is illustrated from living plants. CONCLUSION: Haniffia
santubongensis is the fourth species of Haniffia so far described, and the first
occurring on sandstone.
PMID- 28510940
TI - Comparison of soil bacterial communities in a natural hardwood forest and
coniferous plantations in perhumid subtropical low mountains.
AB - BACKGROUND: The bacterial community of forest soils is influenced by
environmental disturbance and/or meteorological temperature and precipitation. In
this study, we investigated three bacterial communities in soils of a natural
hardwood forest and two plantations of conifer, Calocedrus formosana and
Cryptomeria japonica, in a perhumid, low mountain area. By comparison with our
previous studies with similar temperature and/or precipitation, we aimed to
elucidate how disturbance influences the bacterial community in forest soils and
whether bacterial communities in similar forest types differ under different
climate conditions. RESULTS: Analysis of 16S ribosomal RNA gene clone libraries
revealed that Acidobacteria and Proteobacteria were the most abundant phyla in
the three forest soil communities, with similar relative abundance of various
bacterial groups. However, UniFrac analysis based on phylogenetic information
revealed differences of bacterial communities between natural hardwood forest and
coniferous plantation soils. The diversities of bacterial communities of the
replanted Calocedrus and Cryptomeria forests were higher than that in natural
hardwood forest. The bacterial diversity of these three forest soil were all
higher than those in the same forest types at other locations with less
precipitation or with lower temperature. In addition, the distribution of some of
the most abundant operational taxonomic units in the three communities differed
from other forest soils, including those related to Acidobacteria, alpha-, beta-
and gamma-Proteobacteria. CONCLUSIONS: Reforestation could increase the bacterial
diversity. Therefore, soil bacterial communities could be shaped by the forestry
management practices and climate differences in warm and humid conditions.
PMID- 28510941
TI - Vasorelaxing and antihypertensive activities of synthesized peptides derived from
computer-aided simulation of pepsin hydrolysis of yam dioscorin.
AB - BACKGROUND: We reported that yam dioscorin and its peptic hydrolysates exhibited
ACE inhibition and antihypertensive effects on SHRs, however, the active peptides
are not really isolated until now. Using ACE inhibitory screenings, two penta
peptides, KTCGY and KRIHF, were selected for ex vivo and in vivo experiments.
RESULTS: KTCGY, KRIHF, and captopril were shown to have similar vasodilating
effects against phenylephrine (PE)-induced tensions in rat endothelium-dependent
thoracic aortic rings, however, KTCGYKTCGY (two-repeated KTCGY) and TCGYTCGY (two
repeated TCGY) were showed endothelium-independent vasodilating effects against
PE-induced tensions. KTCGY, KRIHF (10 or 20 mg/kg), and captopril (10 mg/kg) were
used to evaluate antihypertensive activity during 24-h after a single oral
administration to spontaneously hypertensive rats (SHRs). The KTCGY and KRIHF
showed significantly different and reduced the systolic blood pressure of SHRs
compared to the blank. CONCLUSIONS: These results suggest that KTCGY and KRIHF
may contribute important roles in yam dioscorin for regulating blood pressure in
vivo.
PMID- 28510942
TI - In vitro propagation and analysis of secondary metabolites in Glossogyne
tenuifolia (Hsiang-Ju) - a medicinal plant native to Taiwan.
AB - BACKGROUND: Glossogyne tenuifolia Cassini (Hsiang-Ju in Chinese) is a perennial
herb native to Penghu Islands, Taiwan. The herb is a traditional anti-pyretic and
hepatoprotective used in Chinese medicine. Several studies on G. tenuifolia have
demonstrated its pharmacological values of antioxidation, anti-inflammation,
immunomodulation, and cytotoxicity on several human cancer cell lines. Active
compounds, oleanolic acid and luteolin in G. tenuifolia are affected by several
factors, including climatic change, pathogens and agricultural practices. Plant
population of G. tenuifolia has been severely affected and reduced considerably
in natural habitat due to the use of herbicides by farmers. Also, collection of
plant material from the natural habitat is restricted to a few months in a year.
Therefore, the objective of the present study was to develop an efficient
micropropagation protocol for G. tenuifolia. The study also aimed to investigate
the influence of in vitro growth environment on the active compounds in in vitro
shoots, tissue culture raised greenhouse plants; compare the values with wild
plants and commercially available crude drug. RESULTS: Half-strength MS
(Murashige and Skoog) basal medium supplemented with 0.1 mg/L 6-benzyladenine
(BA) and 0.1 mg/L alpha-naphthaleneacetic acid (NAA) induced the maximum average
number of shoots (7.3) per shoot tip explant excised from in vitro grown
seedlings. Induction of rooting in cent percent in vitro shoots with an average
number of 6.6 roots/shoot was achieved on 1/2 strength MS medium supplemented
with 3.0 mg/L indole-3-acetic acid (IAA). The rooted plantlets acclimatized
successfully in the greenhouse with a 100% survival rate. HPLC analysis revealed
that the quantity of oleanolic acid and luteolin in in vitro shoots, tissue
culture plants in the greenhouse, wild type plants and commercial crude drug
varied depending upon the source. The oleanolic acid and luteolin contents were
found to be significantly higher (16.89 mg/g and 0.84 mg/g, respectively) in 3
month old tissue culture raised plants in greenhouse compared to commercially
available crude drug (6.51 mg/g, 0.13 mg/g, respectively). CONCLUSIONS: We have
successfully developed an in vitro propagation protocol for G. tenuifolia which
can expedite its plant production throughout the year. The contents of oleanolic
acid and luteolin in the tissue culture raised plants in the greenhouse were
significantly higher than the marketed crude drug demonstrating the practical
application of the tissue culture technology. These findings may be very useful
in micropropagation, germplasm conservation and commercial cultivation of G.
tenuifolia. So far, there is no published report on tissue culture propagation of
this important medicinal plant species.
PMID- 28510943
TI - Two new species of Begonia sect. Coelocentrum, B. guixiensis and B. longa, from
Sino-Vietnamese limestone karsts.
AB - BACKGROUND: In our recent molecular phylogenetic study of Asian Begonia, two
undescribed species, B. guixiensis sp. ined. (S. Guangxi, China) and B. longa sp.
ined. (Vietnam), were sampled and placed within the strongly supported clade
composed of Begonia sect. Coelocentrum and other co-distributed rhizomatous
species in the Sino-Vietnamese limestone karsts. While Begonia sect. Coelocentrum
has been recircumscribed based on the phylogenetic relationships, B. guixiensis
sp. ined. and B. longa sp. ined. remain illegitimate names. In continuation of
our studies in Asian Begonia, these two new species are described and
illustrated. RESULTS: Begonia guixiensis resembles B. cylindrica in the peltate,
subcoriaceous leaves, differing by the shape of ovary/fruit and the type of
placentation. In aspect, B. longa bears a superficial resemblance to B.
brevipedunculata in leaf shape in particular, differing by many other features
such as the long internodes, shorter petioles and smaller leaves, longer
peduncles and 3-locular ovary. The chromosome number of both new species is
determined as 2n = 30. CONCLUSION: A careful study of the literature, herbarium
specimens and living plants, both in the wild and in cultivation in the
experimental greenhouse, support the recognition of the two new species, which
are described and illustrated herein.
PMID- 28510944
TI - Antioxidant activities of two metallothionein-like proteins from sweet potato
(Ipomoea batatas [L.] Lam. 'Tainong 57') storage roots and their synthesized
peptides.
AB - BACKGROUND: Metallothionein (MT) characterized by their low molecular weight and
high cysteine content. RESULTS: Two recombinant proteins of MT-I and MT-II
overproduced in E. coli (M15) was purified by Ni2+-chelated affinity
chromatography. The molecular mass of MT-I and MT-II are ca. 6,600 and 8,000 Da
as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
PAGE). Total antioxidant status, DPPH radical scavenging activity, reducing power
method, Fe2+-chelating ability, ferric thiocyanate (FTC) method, and protecting
calf thymus DNA against hydroxyl radical-induced damage were studied. The MT-I
and MT-II proteins with a concentration of 100 MUg/mL exhibited the highest
activity (expressed respectively as 61.72 +/- 0.13 and 74.28 +/- 1.15 MUM Trolox
equivalent antioxidative capacity, TEAC) in total antioxidant status test. Like
total antioxidant status, DPPH radical scavenging activity, reducing power, Fe2+
chelating ability, FTC activity, and protecting calf thymus DNA against hydroxyl
radical-induced damage all showed that MT-1 and MT-II proteins have antioxidant
activities. In this study, we also found that antioxidant activities of MT-I and
MT-II increased from 17% and 16% (0 h) to about 26% and 28% (24 h) after 24 h
hydrolysis by trypsin. Smaller peptides increased the antioxidant activities.
Four and three peptides, respectively, from MT-I and MT-II protein sequences for
testing antioxidative activity were synthesized according to tryptic hydrolysis
simulation. The obtained MSSGCK, CGSDCK, LTLEGSSEK, ATEGGHACK, CGNGCGGCK, and
CDPCNCK showed IC50 values of 309.87, 1423.37, 3925.54, 561.32, 300.76, and
610.12 MUM, respectively, when scavenging activity of DPPH radicals (%) was
measured. CONCLUSIONS: These findings mean that a cysteine residue is most
important in antiradical activities. It was suggested that MT-I and MT-II might
contribute their antioxidant activities against hydroxyl and peroxyl radicals.
PMID- 28510945
TI - Fusaric acid induced cell death and changes in oxidative metabolism of Solanum
lycopersicum L.
AB - BACKGROUND: Fusaric acid (FA) has been shown to stimulate the rapid development
of disease symptoms, such as necrosis and foliar desiccation. In this study, we
have evaluated the phytotoxicity of FA on tomato plants (Solanum lycopersicum
L.). FA induced necrotic lesions in detached leaves, which are reminiscent of
hypersensitive response (HR) lesions induced by plant-pathogen interactions and
other abiotic stress factors. RESULTS: FA-treated tomato leaves exhibited visible
necrotic lesion as a result of cell death which was evident by Evans blue
staining, enhanced reactive oxygen species (ROS) levels and DNA degradation.
Changes in the generation of O2.- and H2O2 as well as the activities of
superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) were
examined in FA-treated tomato leaves. It was observed that FA exposure stimulated
oxidative burst in the leaves, resulting in a lasting activation of O2.- and H2O2
production. After first day of FA application, the H2O2 scavenging enzymes CAT
and APX showed a strong activity decrease followed by gradual recovery to the
control level after 2 and 3 days. CONCLUSION: A concomitant increase in ROS
production, the down regulation of antioxidative enzymes activities and
upregulation of lipid peroxidation were crucial for the onset of cell death.
These results suggested that FA-induced damage might result from ROS pathways.
Thus, our experiments provide a useful model plant system for research on FA
induced plant cell death.
PMID- 28510946
TI - Aluminum induces rapidly mitochondria-dependent programmed cell death in Al
sensitive peanut root tips.
AB - BACKGROUND: Although many studies suggested that aluminum (Al) induced programmed
cell death (PCD) in plants, the mechanism of Al-induced PCD and its effects in Al
tolerance is limited. This study was to investigate the mechanism and type of Al
induced PCD and the relationship between PCD and Al tolerance. RESULTS: In this
study, two genotypes of peanut 99-1507 (Al tolerant) and ZH2 (Al sensitive) were
used to investigate Al-induced PCD. Peanut root growth inhibition induced by
AlCl3 was concentration and time-dependent in two peanut varieties. AlCl3 at 100
MUM could induce rapidly peanut root tip PCD involved in DNA cleavage, typical
apoptotic chromatin condensation staining with DAPI, apoptosis related gene
Hrs203j expression and cytochrome C (Cyt c) release from mitochondria to cytosol.
Caspase3-like protease was activated by Al; it was higher in ZH2 than in 99-1507.
Al increased the opening of mitochondrial permeability transition pore (MPTP),
decreased inner membrane potential (DeltaPsim) of mitochondria. Compared with the
control, Al stress increased O2*- and H2O2 production in mitochondria. Reactive
oxygen species (ROS) burst was produced at Al treatment for 4 h. CONCLUSIONS: Al
induced PCD is earlier and faster in Al-sensitive peanut cultivar than in Al
tolerant cultivar. There is a negative relationship between PCD and Al
resistance. Mitochondria- dependence PCD was induced by Al and ROS was involved
in this process. The mechanism can be explained by the model of acceleration of
senescence under Al stress.
PMID- 28510947
TI - Generic affiliations of Canthium species placed under Pyrostria group B sensu
Bridson (Vanguerieae, Rubiaceae) inferred from morphology and molecular data.
AB - BACKGROUND: Pyrostria sensu lato (s.l.) is regarded as one of the polyphyletic
group within Vanguerieae formerly comprising of Pyrostria sensu stricto (s.s.),
Pyrostria group A and Pyrostria group B delineated by the number of locules and
geographical occurrence. Recent molecular phylogenetic studies within the genus
have narrowed its circumscription that resulted in the merging of Pyrostria group
A and Pyrostria s.s. Although some species of Pyrostria group B were already
transferred to Pyrostria s.s. and Psydrax based on morphology, other
representatives of the group remain unsettled. RESULTS: Bayesian and parsimony
analysis of the combined ITS (nrDNA) and trnL-F (cpDNA) datasets showed a well
supported clade of the whole Vanguerieae containing four Philippine endemic
representatives of Pyrostria group B. The placement of Canthium oligophlebium,
Canthium obovatifolium and Canthium ramosii within Pyrostria s.s. (PP = 0.99; BS
= 85%) is robustly supported likewise the affiliation of C. gynochthodes with
Psydrax (PP = 0.94; BS = 85%). Morphological features shared by our species with
Pyrostria s.s. and Psydrax further supports our molecular data. CONCLUSION: Our
study supports the earlier hypothesis that Canthium oligophlebium, C.
obovatifolium and C. ramosii should be placed under Pyrostria s.s. except for C.
gynochthodes that grouped with Psydrax. Four new combinations are proposed in
this study. The generic affiliations of other species of Pyrostria group B should
be reinvestigated towards a more natural classfication in Vanguerieae.
PMID- 28510948
TI - A new variant produced by Rhizoctonia solani AG1-IC isolate CH-1 with a new type
of nuclei.
AB - BACKGROUND: Isolate CH-1 of Rhizoctonia solani Kuhn was commonly used in our
studies of the pathogenicity and genetics of this pathogen. During the
preparation of homokaryons through protoplast regeneration and tuft formation, a
defective homokaryon was detected and a new variant was obtained. RESULTS: When
tuft formation was used to identify the karyotic nature of single protoplast
regenerants (SPRs) of Rhizoctonia solani AG1-IC isolate CH-1, one homokaryon type
designated as A type and the parental heterokaryon designated as AB type were
obtained. The homokaryon B type was not found. Various approaches were used to
obtain SPRs, including from fast or slow growing protoplast regenerants, and from
regenerants of protoplasts released from mycelia grown in different nutrient
broths or at different temperatures. Without exception, all these SPRs were
either homokaryon A or heterokaryon AB. Moreover, the SPRs obtained from
different generations of SPRs, and from different generations of SPRs treated
with lytic enzymes 3 to 4 times also were invariably either homokaryon A or
heterokaryon AB. When single hyphal isolates were obtained from the tuft
resulting from the pairing between homokaryon A and heterokaryon AB, only the
heterokaryon and a variant were obtained. The variant did not form tuft when
paired with parental heterokaryon AB or homokaryon A. Its protoplast regenerants
gave rise to heterokaryon AB, homokaryon A and the variant, indicating that it is
a new kind of heterokaryon. CONCLUSION: Inability to obtain homokaryon B despite
numerous attempts suggests that the B type nuclei are probably defective and are
dependent on A type nuclei for their multiplication. This is the first report of
a heterokaryotic R. solani strain carrying a defective type of nuclei. A new
variant which is a new kind of heterokaryon was obtained from the tuft resulting
from the paring between the homokaryon A and the parental heterokaryon AB.
PMID- 28510949
TI - Thermoregulation in the appendix of the Sauromatum guttatum (Schott)
inflorescence.
AB - BACKGROUND: Three phenolic compounds are capable of activating the process that
simultaneously leads to temperature rise and odor-production in the Sauromatum
appendix. These compounds are salicylic acid, aspirin, and 2,6 dihydroxybenzoic
acid. The objectives of the present study were to examine the effect of various
concentrations of the these inducers on the temperature rise and to study the
effect of mitochondrial inhibitors (KCN and SHAM) and an uncoupler (DNP) on the
temperature rise. RESULTS: In sections of the Sauromatum appendix two successive
temperature rate maxima were detected in the presence of the three inducers. Two
temperature maxima were also detected in appendices of intact inflorescences. The
temperature profiles demonstrated a considerable variability within sections of
one appendix in both magnitude and time of reaching a peak. When the Sauromatum
temperature decreased it returned either to the same temperature baseline or to a
slightly different baseline. The temperature rise was blocked by KCN (20 mM) and
SHAM (40 mM) alone or when added together. DNP, an uncoupler, at 2.5 mM also
blocked the rise in temperature. The thermogenic inducers also triggered a
temperature rise in Arum appendix. CONCLUSIONS: The presence of two rate maxima
may indicate different heat-generating sources. The blockage of the temperature
rise in the presence of KCN or SHAM implies that the activity of the cyanide
resistant and -sensitive pathways is required for generating heat. The
variability in temperature profiles maybe related to changes in cellular control
factors. This study provides the basis for investigating thermoregulation in
plants.
PMID- 28510950
TI - Arbuscular mycorrhizal fungi increase salt tolerance of apple seedlings.
AB - BACKGROUND: Apple trees are often subject to severe salt stress in China as well
as in the world that results in significant loss of apple production. Therefore
this study was carried out to evaluate the response of apple seedlings inoculated
with abuscular mycorrhizal fungi under 0, 20/00, 40/00 and 60/00 salinity stress
levels and further to conclude the upper threshold of mycorrhizal salinity
tolerance. RESULTS: The results shows that abuscular mycorrhizal fungi
significantly increased the root length colonization of mycorrhizal apple plants
with exposure time period to 0, 20/00 and 40/00 salinity levels as compared to
non-mycorrhizal plants, however, percent root colonization reduced as saline
stress increased. Salinity levels were found to negatively correlate with leaf
relative turgidity, osmotic potential irrespective of non-mycorrhizal and
mycorrhizal apple plants, but the decreased mycorrhizal leaf turgidity maintained
relative normal values at 20/00 and 40/00 salt concentrations. Under salt stress
condition, Cl- and Na+ concentrations clearly increased and K+ contents obviously
decreased in non-mycorrhizal roots in comparison to mycorrhizal plants, this
caused mycorrhizal plants had a relatively higher K+/Na+ ratio in root. In
contrast to zero salinity level, although ascorbate peroxidase and catalase
activities in non-inoculated and inoculated leaf improved under all saline
levels, the extent of which these enzymes increased was greater in mycorrhizal
than in non-mycorrhizal plants. The numbers of survived tree with non
mycorrhization were 40, 20 and 0 (i.e., 66.7%, 33.3% and 0) on the days of 30, 60
and 90 under 40/00 salinity, similarly in mycorrhization under 60/00 salinity 40,
30 and 0 (i.e., 66.7%, 50% and 0) respectively. CONCLUSION: These results suggest
that 20/00 and 40/00 salt concentrations may be the upper thresholds of salinity
tolerance in non-mycorrhizal and mycorrhizal apple plants, respectively.
PMID- 28510951
TI - Hyphoderma pinicola sp. nov. of H. setigerum complex (Basidiomycota) from Yunnan,
China.
AB - BACKGROUD: Hyphoderma setigerum (Fr.) Donk is a white-rot wood-decaying corticoid
fungal species. It occurs worldwide from tropical to temperate regions. However,
taxonomic studies in recent decades showed that H. setigerum is a species complex
with four separate species, before this study. RESULTS: Hyphoderma pinicola sp.
nov. was collected on dead wood of Pinus yunnanensis Franch. in the temperate
montane belt at 2200-2400 m altitudes, in Yunnan Province of China. Within the H.
setigerum complex this new taxon is distinguished by having 2-sterigmate basidia,
long basidiospores, and nearly naked septocystidia. A description and
illustrations of this new species are provided, along with a key to five species
of the H. setigerum complex. Phylogenetic reconstruction based on 5.8S-ITS2
sequences indicated that H. pinicola belongs to the H. setigerum complex and has
a separate position within the clade including H. subsetigerum and H. setigerum
s.s. Bayesian inference of phylogeny based on two datasets, ITS and 28S nuclear
ribosomal DNA sequences, confirmed the independent status of H. pinicola.
CONCLUSION: Morphological and phylogenetic studies showed that H. pinicola
represents a fifth species of H. setigerum complex.
PMID- 28510952
TI - Analysis of microsatellites in the vulnerable orchid Gastrodia flavilabella: the
development of microsatellite markers, and cross-species amplification in
Gastrodia.
AB - BACKGROUND: Gastrodia flabilabella is a mycoheterotrophic orchid that obtains
carbohydrates and nutrients from its symbiotic mycorrhizal fungi. The species is
an endemic and vulnerable species enlisted in the "A Preliminary Red List of
Taiwanese Vascular Plants" according to the IUCN Red List Categories and Criteria
Version 3.1. G. flabilabella dwells the underground of broadleaf and coniferous
forest with richness litter. Based on herbarium records, this species is
distributed in central Taiwan. Twenty eight microsatellite loci were developed in
G. flabilabella and were tested for cross-species amplification in additional
taxa of G. confusoides, G. elata, and G. javanica. We estimated the genetic
variation that is valuable for conservation management and the development of the
molecular identification system for G. elata, a traditional Chinese medicine
herb. RESULTS: Microsatellite primer sets were developed from G. flabilabella
using the modified AFLP and magnetic bead enrichment method. In total, 257
microsatellite loci were obtained from a magnetic bead enrichment SSR library. Of
the 28 microsatellite loci, 16 were polymorphic, in which the number of alleles
ranged from 2 to 15, with the observed heterozygosity ranging from 0.02 to 1.00.
In total, 15, 13, and 7 of the loci were found to be interspecifically
amplifiable to G. confusoides, G. elata, and G. javanica, respectively.
CONCLUSIONS: Amplifiable and transferable microsatellite loci are potentially
useful for future studies in investigating intraspecific genetic variation,
reconstructing phylogeographic patterns among closely related species, and
establishing the standard operating system of molecular identification in
Gastrodia.
PMID- 28510954
TI - Hydraulic conductivity and contribution of aquaporins to water uptake in roots of
four sunflower genotypes.
AB - BACKGROUND: This article evaluates the potential of intraspecific variation for
whole-root hydraulic properties in sunflower. We investigated genotypic
differences related to root water transport in four genotypes selected because of
their differing water use efficiency (JAC doi: 10.1111/jac.12079. 2014). We used
a pressure-flux approach to characterize hydraulic conductance (L 0 ) which
reflects the overall water uptake capacity of the roots and hydraulic
conductivity (Lp r ) which represents the root intrinsic water permeability on an
area basis. The contribution of aquaporins (AQPs) to water uptake was explored
using mercuric chloride (HgCl2), a general AQP blocker. RESULTS: There were
considerable variations in root morphology between genotypes. Mean values of L 0
and Lp r showed significant variation (above 60% in both cases) between
recombinant inbred lines in control plants. Pressure-induced sap flow was
strongly inhibited by HgCl2 treatment in all genotypes (more than 50%) and
contribution of AQPs to hydraulic conductivity varied between genotypes. Treated
root systems displayed markedly different L 0 values between genotypes whereas Lp
r values were similar. CONCLUSIONS: Our analysis points to marked differences
between genotypes in the intrinsic aquaporin-dependent path (Lp r in control
plants) but not in the intrinsic AQP-independent paths (Lp r in HgCl2 treated
plants). Overall, root anatomy was a major determinant of water transport
properties of the whole organ and can compensate for a low AQP contribution.
Hydraulic properties of root tissues and organs might have to be taken into
account for plant breeding since they appear to play a key role in sunflower
water balance and water use efficiency.
PMID- 28510955
TI - Molecular cloning and characterization of a thioredoxin from Taiwanofungus
camphorata.
AB - BACKGROUND: Thioredoxin (Trx) is reduced by thioredoxin reductase. Trx is used in
ribonucleoide reduction, assimilatory sulfate reduction, in modulation of protein
sulfhydryl groups, and refolding proteins. RESULTS: A TcTrx (Tc: Taiwanofungus
camphorata) cDNA (640 bp, GenBank AY838902.1) encoding a putative thioredoxin
(Trx) of 135 amino acid residues with calculated molecular mass of 16.17 kDa was
cloned from Taiwanofungus c amphorata. The deduced amino acid sequence containing
a motif (Cys-Gly-Pro-Cys) that is highly conserved among the reported Trxs. A
three dimensional structural model of the TcTrx has been created based on the
known structure of Malassezia sympodialis Trx (MsTrx, PDB ID: 2j23). To
characterize the TcTrx, the codon optimized coding region was subcloned into an
expression vector and transformed into Saccharomyces cerevisiae. The recombinant
His8-tagged TcTrx was expressed and purified by Ni affinity chromatography. The
purified enzyme showed a band of approximately 32 kDa (expected dimeric form) on
a 12% SDS-PAGE. The molecular mass determined by MALDI-TOF is 33.16 kDa which
suggests that the purified enzyme is a dimeric enzyme. Furthermore, the enzyme
exhibited TcTrx activity via insulin assay. The Michaelis constant (K M ) value
for insulin was 3.78 * 10-2 mM. The enzyme's half-life of deactivation was 13 min
at 45 degrees C. The enzyme was most active at pH 7. CONCLUSIONS: A three
dimensional structural model of T. camphorata Trx based on its TcTrx cDNA
sequence. The active form of the TcTrx has been successfully expressed in yeast.
The enzyme possesses Trx activity and is capable of reduction of disulfide bonds
during the formation of newly synthesized proteins.
PMID- 28510953
TI - Microsatellite resources of Eucalyptus: current status and future perspectives.
AB - Eucalyptus is the premier paper pulp, short rotation plantation species grown all
over the world. Genetic improvement programs integrating molecular marker tools
are in progress in many parts of the globe to increase the productivity. Whole
genome sequence and expressed sequence tags (ESTs) of the eucalypts paved way for
introduction of molecular genetics and breeding in this genus. Different
molecular characterization approaches have been used simultaneously in eucalypts,
however, microsatellites or simple sequence repeats (SSRs) with their prolific
characteristics could occupy a special niche in Eucalyptus genetic improvement.
Further, highly informative SSRs were used for the clonal identity, genetic
fidelity and in certification of breeder's rights. Eucalyptus genetic linkage
maps generated with microsatellite loci were used successfully to identify
quantitative trait loci (QTLs) for various economically important traits.
Progressively more numbers of microsatellites are being linked to genes
associated with adaptive and functional variations, therefore making their
utility broader in genetic applications. Availability of common SSR markers
across the species provides an opportunity to validate the expression of QTLs
across variable genetic backgrounds and accurately compare the position of QTLs
in other species. Recent evidences suggest that the presence of SSRs in micro
RNAs of plant species play a role in the quantitative trait expression. Similar
studies in eucalypts may provide new insights into the genetic architecture of
transcript-level variations and post transcriptional gene regulation. This review
on eucalypts microsatellites, highlights the availability and characteristics of
genomic and eSSRs and their potential in genetic analysis of natural and breeding
populations and also discusses the future prospects in population genetics and
marker assisted selection.
PMID- 28510956
TI - Essential oil variation in wild populations of Artemisia saharae (Asteraceae)
from Tunisia: chemical composition, antibacterial and antioxidant properties.
AB - BACKGROUND: Artemisia saharae Pomel is a new taxon of Artemisia herba-alba Asso
(Asteraceae) which is endemic to Tunisia and Algeria. This shrub, commonly known
as white wormwood or desert wormwood, is largely used in folk medicine and as a
culinary herb. The bulks aromatic plants come from wild populations whose
essential oils compositions as well as their biological properties are severely
affected by several factors such as geographic conditions. Therefore, the aim of
the present work is to provide more information about the influence of altitude
variation on the essential oil composition, antimicrobial and antioxidant
properties of Artemisia saharae growing wild in the same geographical area.
RESULTS: Essential oils were extracted by hydrodistillation of leaves and flowers
of the plant collected from seven different altitudes of the Baten Zamour region
(southwest of Tunisia). The highest essential oil yields (2.70-2.80%) were
obtained for populations of high altitudes. Seventy-five compounds, representing
92.78 to 96.95% of the total essential oils, were separated and identified.
Essential oils were characterized by very high percentage of oxygenated
monoterpenes (52.1-72.6%) which constituted the predominant class. From the
analyzed populations, the major compounds (>7%) were alpha-thujone, beta-thujone,
chrysanthenone, camphor, chrysanthenyl acetate, and sabinyl acetate. Sabinyl
acetate which was detected in some populations at relatively high percentages
(7.7-10.8%) seems to be characteristic to Southern Tunisian A. saharae. The
studied essential oil showed a chemical diversity depending on the population
altitude as revealed by linear discriminant and cluster analyses. CONCLUSIONS:
Three population groups associated with altitudinal levels were distinguished. It
is worthy to note that the most discriminating compounds of chemical groups were
the minor ones. Despite the high variation of essential oil compositions, the
high altitude population did not affect severely the antibacterial activity
against the most tested strains. Altitude seems to be an important factor
influencing the yield and the chemical profile of Artemisia saharae essential
oils. Knowledge of the chemical composition of essential oils in relation to
environmental factors is a very important quality criterion for their marketing
and contributes to their valorization as functional ingredient in food
technology.
PMID- 28510957
TI - Antioxidant, cell-protective, and anti-melanogenic activities of leaf extracts
from wild bitter melon (Momordica charantia Linn. var. abbreviata Ser.)
cultivars.
AB - BACKGROUND: Several wild bitter melon (WBM; Momordica charantia Linn. var.
abbreviata Ser.) cultivars were developed in Taiwan. However, little information
is available regarding biological function of WBM leaf. Therefore, the objectives
of this study were to investigate the nutrient content, antioxidant, cell
protection and anti-melanogenic properties of wild bitter melon leaf. RESULTS:
Methanolic leaf extracts were prepared from a variety and two cultivars of WBM.
All extracts exerted potent nitric oxide and hydroxyl radical scavenging
capacities. Furthermore, all extracts effectively reduce the production of
reactive oxygen species and prevent cell death in UVB-irradiated HaCaT
keratinocytes. The cell protective effect of leaf extract was also investigated
by the prevention of HaCaT cells from sodium nitroprusside or menadione-induced
toxicity, and significant cyto-protective activities were observed for all of
them. Additionally, all extracts significantly suppressed tyrosinase activity and
melanin levels in B16-F10 melanocytes. CONCLUSIONS: WBM leaf extract showed
significant antioxidant, cyto-protective and anti-melanogenic activities. These
findings suggested that WBM leaves may be beneficial for preventing the photo
oxidative damage and melanogenesis of skin.
PMID- 28510959
TI - Fire induced reproductive mechanisms of a Symphoricarpos (Caprifoliaceae) shrub
after dormant season burning.
AB - BACKGROUND: Symphoricarpos, a genus of the Caprifoliaceae family, consists of
about 15 species of clonal deciduous shrubs in North America and 1 species
endemic to China. In North American tallgrass prairie, Symphoricarpos orbiculatus
(buckbrush) is the dominant shrub often forming large colonies via sexual and
asexual reproductive mechanisms. Symphoricarpos shrubs, in particular S.
orbiculatus, use a unique sexual reproductive mechanism known as layering where
vertical stems droop and the tips root upon contact with the soil. Because of
conflicting societal values of S. orbiculatus for conservation and agriculture
and the current attempt to restore historical fire regimes, there is a need for
basic research on the biological response of S. orbiculatus to anthropogenic
burning regimes. RESULTS: From 2007 through 2013 we applied prescribed fires in
the late dormant season on grazed pastures in the Grand River Grasslands of Iowa.
From 2011 to 2013, we measured how S. orbiculatus basal resprouting and layering
stems were affected by patchy fires on grazed pastures, complete pasture fires on
grazed pastures or fire exclusion without grazing for more than three years. We
measured ramet height, ramet canopy diameter, stems per ramet, ramets per 100 m2,
and probability of new layering stems 120 days after fire. Height in burned plots
was lower than unburned plots but S. orbiculatus reached ~ 84% of pre-burn height
120 days after fire. Stems per ramet were 2x greater in the most recently burned
plots due to basal re-sprouting. Canopy diameter and density of ramets was not
affected by time since fire, but burned pastures had marginally lower densities
than plots excluded from fire (P = 0.07). Fire triggered new layering stems and
no new layering stems were found in plots excluded from fire. CONCLUSIONS: The
mechanisms of both basal sprouting and aerial layering after fire suggest S.
orbiculatus is tolerant to dormant season fires. Furthermore, dormant season
fires, regardless if they were patchy fires or complete pasture fires, did not
result in mortality of S. orbiculatus. Dormant season fires can reduce S.
orbiculatus structural dominance and maintain lower ramet densities but also
trigger basal resprouting and layering.
PMID- 28510958
TI - The blue fluorescent protein from Vibrio vulnificus CKM-1 is a useful reporter
for plant research.
AB - BACKGROUND: The mBFP is an improved variant of NADPH-dependent blue fluorescent
protein that was originally identified from the non-bioluminescent pathogenic
bacteria Vibrio vulnificus CKM-1. To explore the application of mBFP in plants,
the mBFP gene expression was driven by one of the three promoters, namely, leaf
specific (RbcS), hypoxia-inducible (Adh) or auxin-inducible (DR5) promoters, in
different plant tissues such as leaves, roots and flowers under diverse
treatments. In addition, the expressed mBFP protein was targeted to five
subcellular compartments such as cytosol, endoplasmic reticulum, apoplast,
chloroplast and mitochondria, respectively, in plant cells. RESULTS: When the
mBFP was transiently expressed in the tobacco leaves and floral tissues of moth
orchid, the cytosol and apoplast exhibited brighter blue fluorescence than other
compartments. The recombinant mBFP-mS1C fusion protein exhibited enhanced
fluorescence intensity that was correlated with more abundant RNA transcripts
(1.8 fold) as compared with a control. In the root tips of horizontally grown
transgenic Arabidopsis, mBFP could be induced as a reporter under hypoxia
condition. Furthermore, the mBFP was localized to the expected subcellular
compartments, except that dual targeting was found when the mBFP was fused with
the mitochondria-targeting signal peptide. Additionally, the brightness of mBFP
blue fluorescence was correlated with NADPH concentration. CONCLUSION: The NADPH
dependent blue fluorescent protein could serve as a useful reporter in plants
under aerobic or hypoxic condition. However, to avoid masking the mitochondrial
targeting signal, fusing mBFP as a fusion tag in the C-terminal will be better
when the mBFP is applied in mitochondria trafficking study. Furthermore, mBFP
might have the potential to be further adopted as a NADPH biosensor in plant
cells. Future codon optimization of mBFP for plants could significantly enhance
its brightness and expand its potential applications.
PMID- 28510960
TI - Ontogeny of the extrafloral nectaries of Vigna adenantha (Leguminosae, Phaseolae)
and its relation with floral development.
AB - BACKGROUND: The inflorescences of the genus Vigna Savi have extrafloral nectaries
(EFNs) among the flowers whose origin is still unknown. The disposition, anatomy
and morphology, as well as the ontogeny of the extrafloral nectaries (EFNs)
associated with the inflorescences of Vigna adenantha (G.F.W. Meyer) Marechal,
Mascherpa & Stainier (Leguminosae, Papilionoideae, Phaseolae) were studied.
Besides, the ultrastructure of the secretory stage was described. RESULTS: The
inflorescence, a raceme, bears a brief globose secondary axis in each node with 2
flowers and 5-7 EFNs, which develop in acropetal direction. Each EFN originates
from the abscission of a flower bud that interrupts its development, resulting in
an elevated EFN. This secretory structure is formed by a ring of epidermal and
parenchymatic cells surrounding a group of elongated central cells. The nectary
is irrigated by phloem and xylem. Four developmental stages proceed; each one
relates to a different embryological stage of the flowers in each secondary axis.
CONCLUSIONS: The first functional EFN of each secondary axis of the inflorescence
reaches its maturity when both the pollen grains and the embryo sacs are
completely developed and the flowers begin to open. The secretion is
granulocrine. The following EFNs develop in the same way.
PMID- 28510961
TI - Chlorophyll and carbohydrate metabolism in developing silique and seed are
prerequisite to seed oil content of Brassica napus L.
AB - BACKGROUND: Although the seed oil content in canola is a crucial quality
determining trait, the regulatory mechanisms of its formation are not fully
discovered. This study compared the silique and seed physiological
characteristics including fresh and dry weight, seed oil content, chlorophyll
content, and carbohydrate content in a high oil content line (HOCL) and a low oil
content line (LOCL) of canola derived from a recombinant inbred line in 2010,
2011, and 2012. The aim of the investigation is to uncover the physiological
regulation of silique and seed developmental events on seed oil content in
canola. RESULTS: On average, 83% and 86% of silique matter while 69% and 63% of
seed matter was produced before 30 days after anthesis (DAA) in HOCL and LOCL,
respectively, over three years. Furthermore, HOCL exhibited significantly higher
fresh and dry matter at most developmental stages of siliques and seeds. From 20
DAA, lipids were deposited in the seed of HOCL significantly faster than that of
LOCL, which was validated by transmission electron microscopy, showing that HOCL
accumulates considerable more oil bodies in the seed cells. Markedly higher
silique chlorophyll content was observed in HOCL consistently over the three
consecutive years, implying a higher potential of photosynthetic capacity in
siliques of HOCL. As a consequence, HOCL exhibited significantly higher content
of fructose, glucose, sucrose, and starch mainly at 20 to 45 DAA, a key stage of
seed lipid deposition. Moreover, seed sugar content was usually higher than
silique indicating the importance of sugar transportation from siliques to seeds
as substrate for lipid biosynthesis. The much lower silique cellulose content in
HOCL was beneficial for lipid synthesis rather than consuming excessive
carbohydrate for cell wall. CONCLUSIONS: Superior physiological characteristics
of siliques in HOCL showed advantage to produce more photosynthetic assimilates,
which were highly correlated to seed oil contents.
PMID- 28510962
TI - How do leaf anatomies and photosynthesis of three Rhododendron species relate to
their natural environments?
AB - BACKGROUND: Rhododendron is one of the most well-known alpine flowers. In order
to identify performances relating to Rhododendron's natural habitats we
investigated the leaf anatomical structures and photosynthetic characteristics of
R. yunnanense, R. irroratum and R. delavayi, which showed different responses
after being transplanted into a common environment. RESULTS: When compared with
R. irroratum and R. delavayi, R. yunnanense had lower leaf dry mass per unit area
(LMA) and larger stomata, but smaller stomatal density (SD) and total stomata
apparatus area percent (At), lower stomatal conductance (Gs), transpiration rate
(Tr), light compensation point (LCP), light saturation point (LSP), light
saturated photosynthetic rate (Amax) and leaf nitrogen content per unit area
(Na). LMA was positively correlated with Amax and maximum rates of carboxylation
(Vcmax). However, leaf N content was not significantly correlated with Amax.
Thus, the variation in leaf photosynthesis among species was regulated largely by
changes in LMA, rather than the concent of nitrogen in leaf tissue. CONCLUSIONS:
R. yunnanense plants are vulnerable to moisture and light stress, while R.
irroratum and R. delavayi are better suited to dry and high radiation
environments. The present results contribute to our understanding physiological
trait divergence in Rhododendron, as well benefit introduction and domestication
efforts for the three species of Rhododendron studied in this work.
PMID- 28510964
TI - Occurrence, types and distribution of calcium oxalate crystals in leaves and
stems of some species of poisonous plants.
AB - BACKGROUND: Calcium oxalate crystals, which are found in many organs of plants,
have different morphological forms: as druses, prism, styloids, raphides and
crystal sand. In this study, the distribution, type and specific location of
calcium oxalate crystals in the leaves and stems of the eight species of
poisonous plants and one species of nonpoisonous plant were investigated with
light microscopy. During study special attention was given to the possible
correlation between the presence and types of calcium oxalate crystals and toxic
plant organs. The plants examined in this study were Hedera helix L.
(Araliaceae), Aristolochia clematitis L. (Aristolochiaceae), Humulus lupulus L.
(Cannabaceae), Saponaria officinalis L. (Caryophyllaceae), Chelidonium majus L.
(Papaveraceae), Hypericum perforatum L. (Hypericaceae), Tribulus terrestris L.
(Zygophyllaceae), Cynanchum acutum L. (Asclepiadaceae), and Nerium oleander L.
(Apocynaceae). RESULTS: Three types of crystals: druses, prismatic crystals and
crystal sands were observed. Druses were identified in the leaves and stems of
six species of studied plants. In contrast to druses, crystal sands and prismatic
crystals were rare. Prismatic crystals were observed in the leaf mesophlly cells
of both Nerium oleander and Cynanchum acutum. However, crystal sands were
observed only in the pith tissue of Humulus lupulus. On the other hand, leaves
and stems of Chelidonium majus, Aristolochia clematitis and Hypericum perforatum
were devoid of crystals. CONCLUSION: There is no absolute correlation between the
presence and type of calcium oxalate crystals and toxic plant organs. However
druse crystals may function as main irritant in toxic organs of the plants.
PMID- 28510963
TI - How plants cope with heavy metals.
AB - Heavy metals are naturally occurring in the earth's crust but anthropogenic and
industrial activities have led to drastic environmental pollutions in distinct
areas. Plants are able to colonize such sites due to several mechanisms of heavy
metal tolerance. Understanding of these pathways enables different fruitful
approaches like phytoremediation and biofortification.Therefore, this review
addresses mechanisms of heavy metal tolerance and toxicity in plants possessing a
sophisticated network for maintenance of metal homeostasis. Key elements of this
are chelation and sequestration which result either in removal of toxic metal
from sensitive sites or conduct essential metal to their specific cellular
destination. This implies shared pathways which can result in toxic symptoms
especially in an excess of metal. These overlaps go on with signal transduction
pathways induced by heavy metals which include common elements of other signal
cascades. Nevertheless, there are specific reactions some of them will be
discussed with special focus on the cellular level.
PMID- 28510965
TI - Salt tolerance mechanisms in Salt Tolerant Grasses (STGs) and their prospects in
cereal crop improvement.
AB - Increasing soil salinity in the agricultural fields all over the world is a
matter of concern. Salinity poses a serious threat to the normal growth and
development of crop plants. What adds to the concern is that all the cereal crops
are sensitive to increasing soil salinity. So it is implacable to either search
for salinity resistant varieties of crop plants or transform them genetically to
sustain growth and reproducibility at increasing salinity stress. For the second
perspective, mining the salt tolerant genes in the close relatives of cereal
crops apparently becomes important, and most specifically in the salt tolerant
grasses (STGs). STGs include the halophytes, facultative halophytes and salt
tolerant glycophytes of the family Poaceae. In this review the potentiality of
STGs has been evaluated for increasing the salinity tolerance of cereal crops.
STGs are capable of surviving at increasing salt stress by utilizing different
mechanisms that include vacuolization of toxic Na+ and Cl- in mature or senescing
leaves, secretion of excess salts by salt glands, accumulation of osmolytes like
proline and glycine betaine, and scavenging of ROS by antioxidative enzymes. The
STGs are a therefore a potent source of salt tolerant genes.
PMID- 28510966
TI - From leaf and branch into a flower: Magnolia tells the story.
AB - BACKGROUND: In the classical doctrines, Magnolia was frequently considered the
archetype among flowering plants, and its conduplicate carpel with marginal
placentation was assumed to be derived from a leaf-like organ bearing ovules
along its margins. Although the robustness of this concept has been seriously
questioned by advances in botanical research, especially the emergence of
Magnolia deeper in the angiosperm tree of life in molecular systematics, it
remains the most-taught interpretation for the origin of carpels. RESULTS: To
test the validity of this classical doctrine, we performed comparative anatomical
analyses of the vascular bundles in the flowers of Magnolia using fine (8-MUm)
paraffin -sections. We document the presence of two independent vascular systems
in the carpels: the collateral bundles of the dorsal and ventral veins arising
from the stelar bundle, and the amphicribral ovular bundles arising from the
cortical bundles. This observation in conjunction with data from other fields
concurrently suggests that the ovary wall is equivalent to a foliar organ whereas
the placenta represents an ovule-bearing shoot. CONCLUSIONS: Our observation on
the former model plant, Magnolia, nullifies the classical doctrine of carpel
evolution and supports the Unifying Theory. This conclusion prompts a
reconsideration of the concept of angiosperm flower evolution.
PMID- 28510967
TI - Characterization of a fungicidal substance produced by Eupenicillium brefeldianum
isolated from soil for plant disease control and its significance in nature.
AB - BACKGROUND: A fungus identified as Eupenicillium brefeldianum was isolated from
soil amended with vegetable tissues. RESULT: When grown in liquid medium prepared
from the same vegetable tissues, E. brefeldianum produced a substance capable of
preventing disease development of leaf spots of mustard cabbage caused by
Alternaria brassicicola and inhibiting the germination of A. brassicicola
conidia. The inhibitory substance was fungicidal and was very stable under high
temperature and extreme pH. It was soluble in polar solvents but not soluble in
non-polar solvents, and did not have charges on its molecule. This is the first
discovery of the production of a fungicidal substance by this fungus. CONCLUSION:
Results from this study suggest the possession of a strong competitive
saprophytic ability by E. brefeldianum, which in turn may explain the widespread
occurrence of this fungus in soils.
PMID- 28510968
TI - Multiple resistance-activating substances produced by Humicola phialophoroides
isolated from soil for control of Phytophthora blight of pepper.
AB - BACKGROUND: Microorganisms capable of utilizing vegetable tissues for
multiplication in soil were isolated, cultivated in liquid medium prepared from
the same vegetable tissues, and tested for ability to activate resistance in
pepper leaves against Phytophthora blight caused by Phytophthora capsici.
RESULTS: Among the 121 microorganisms isolated, a fungus Humicola phialophoroides
showed distinct ability to produce substances capable of activating resistance.
The resistance-activating substances produced by H. phialophoroides were mostly
retained in the mycelium, and were readily extracted from the mycelium powder
with polar solvents. The extract was not inhibitory to zoospore germination or
germ tube growth of P. capsici. In pepper leaves, the extract took only about 12
h to activate resistance against P. capsici. After activation, washing treated
leaf surface with water did not have much effect on the resistance expression. In
addition to being able to move from the upper leaf surface to lower leaf surface,
the resistance-activating substances were capable of moving 5 mm acropetally and
10 mm basipetally in pepper leaves, Chromatography of the extract on silica gel
column suggests that there are probably more than three components in the extract
with resistance-activating ability. The resistance-activating activity of the
mycelium extract was not affected by treatment with either cation or anion
exchange resins, indicating that none of the active components have positive or
negative charges on their molecules. CONCLUSION: Results show that H.
phialophoroides is capable of producing multiple resistance-activating substances
which are mostly retained in the mycelium. The study also indicates that none of
the active components have positive or negative charges on their molecules.
PMID- 28510971
TI - Construction of a high-quality genomic BAC library for Chinese peanut cultivar
Zhonghua 8 with high oil content.
AB - BACKGROUND: Arachis hypogaea L. (2n = 4* = 40, AABB) is one of the most important
oil and economic crop plants in the word. This species has the largest genome
size of about 2,813 Mb among the oil crop species. Zhonghua 8 is a peanut
cultivar planted widely in central China and has several superior traits
including high oil content, high yield and disease resistance. A high-quality BAC
library of Zhonghua 8 was constructed for future researches on the genomics of
Chinese peanut cultivars. RESULTS: A Hin d III-digested genomic BAC (bacterial
artificial chromosome) library was constructed with the genomic DNA from leaves
of Zhonghua 8. This BAC library consists of 160,512 clones and the average insert
is estimated about 102 kb ranging from 30 to 150 kb. The library represents about
5.55* haploid genome equivalents, and provides a 99.71% probability of finding
specific genes. The empty-vector rate is under 5 percent detected from 200
randomly selected clones. Probing of 384 clones with the psbA gene of barley
chloroplast and the atp6 gene of rice mitochondrion indicated that the
contamination with organellar DNA is insignificant. Successive subculture of
three clones showed that the inserts are stable in one hundred generations.
CONCLUSIONS: This study presented the construction of a high-quality BAC library
for the genome of Chinese cultivated peanut. Many essential experiences were
summarized in the present study. This BAC library can serve as a substantial
platform for development of molecular marker, isolation of genes and further
genome research.
PMID- 28510970
TI - Inhibition of ABA-induced stomatal closure by fusicoccin is associated with
cytosolic acidification-mediated hydrogen peroxide removal.
AB - BACKGROUND: Fusicoccin (FC), a fungal phytotoxin produced by Fusicoccum amygdale,
causes the inhibition of ABA-induced stomatal closure. The mechanism of
inhibition is remaining unclear. We analyzed the role of hydrogen peroxide (H2O2)
and relationship between H2O2 removal and cytosolic pH changes during inhibition
of ABA-induced stomatal closure by FC. RESULTS: According to the results, ABA
treatment induced H2O2 production and stomatal closure, but FC inhibited the
effects of ABA on these two parameters. Treatment with catalase (CAT) and NADPH
oxidase inhibitor diphenylene iodonium (DPI) mimicked the effect of FC. These
data suggest that inhibition of ABA effect by FC is related to the decrease of
H2O2 levels in guard cells. Furthermore, similar to CAT, FC not only suppressed
stomatal closure and H2O2 levels in guard cells treated with exogenous H2O2, but
also reopened the stomata which had been closed by ABA and reduced the level of
H2O2 that had been produced by ABA, indicating that FC causes H2O2 removal in
guard cells. The butyric acid treatment simulated the effects of FC on the
stomatal aperture and H2O2 levels in guard cells treated with exogenous H2O2 and
had been closed by ABA, and both FC and butyric acid reduced cytosolic pH in
guard cells of stomata treated with H2O2 and had been closed by ABA, which
demonstrate that cytosolic acidification mediates FC-induced H2O2 removal.
CONCLUSION: These results suggest that FC causes cytosolic acidification in guard
cells, then induces H2O2 removal and reduces H2O2 levels in guard cells, finally
inhibits stomatal closure induced by ABA.
PMID- 28510972
TI - Floral development of Dieffenbachia and the occurrence of atypical flowers in
Araceae.
AB - BACKGROUND: The floral development of Dieffenbachia seguine (N. J. Jacquin)
Schott is analysed in relation to the molecular phylogeny of the Spathicarpae by
Cusimano et al. (Am J Bot 98:654-668, 2011). RESULTS: The initiation of discoid
floral primordia occurs acropetally on the surface of the spadix. Female flowers,
atypical bisexual flowers, sterile male flowers, and male flowers share the same
phyllotactic spirals on the spadix. Four or five stamen primordia are initiated
simultaneously on the periphery of the male floral meristem. During early stages
of stamen initiation, individual stamen primordia are connate at their base. In a
synandrium, stamen fusion occurs very early during their developmental cycle with
the stamens being already united laterally when longitudinal elongation occurs.
The staminodes are also initiated on the periphery of the discoid floral
primordium, and their number varies from four to six. The development of the
fused staminodes will eventually form a longitudinal cavity in the center of the
mature synandrode. The atypical flowers located in the intermediate zone range in
morphology from aborted female flowers to rudimentary sterile male flowers with
incomplete staminodes. CONCLUSIONS: The development of the female flower of
Dieffenbachia Schott presents some similarities with atypical bisexual flowers of
Cercestis Schott representing one of three types of aberrant flower forms in the
family. From a developmental point of view and in the context of a phylogeny of
the group, we believe that the presence of staminodes in the female zone
constitutes a plesiomorphy in the tribe Spathicarpeae.
PMID- 28510969
TI - Role of L-ascorbate in alleviating abiotic stresses in crop plants.
AB - L-ascorbic acid (vitamin C) is a major antioxidant in plants and plays a
significant role in mitigation of excessive cellular reactive oxygen species
activities caused by number of abiotic stresses. Plant ascorbate levels change
differentially in response to varying environmental stress conditions, depending
on the degree of stress and species sensitivity. Successful modulation of
ascorbate biosynthesis through genetic manipulation of genes involved in
biosynthesis, catabolism and recycling of ascorbate has been achieved. Recently,
role of ascorbate in alleviating number of abiotic stresses has been highlighted
in crop plants. In this article, we discuss the current understanding of
ascorbate biosynthesis and its antioxidant role in order to increase our
comprehension of how ascorbate helps plants to counteract or cope with various
abiotic stresses.
PMID- 28510973
TI - Potential preventive role of Iranian Achillea wilhelmsii C. Koch essential oils
in acetaminophen-induced hepatotoxicity.
AB - BACKGROUND: The essential oil of Achillea wilhelmsii C. Koch (100 & 200 mg/kg
b.w, i.p) was evaluated against acetaminophen induced hepatic injuries in rats.
For this purpose, the activities of cytochrome P450 (CYP450), glutathione s
transferase (GST) and markers of liver injuries (ALT, AST, ALP) together with
level of GSH measured analytically in time intervals (2, 4, 8, 16 & 24 h) after
treatments confirmed by histophatological consideration in rat livers. RESULTS:
Administration of acetaminophen (500 mg/kg bw, i.p) significantly increased the
activity of CYP450 concomitant with increasing the release of ALT and AST.
Whereas, GSH level and GST activity were decreased significantly after
acetaminophen treatment. Treatment of rats with Achillea wilhelmsii essential
oils significantly modulate these parameters to normal values. Also,
histophatological analysis of liver biopsies was consistent with the biochemical
findings. CONCLUSION: The data led us to conclude the curative potential of
Achillea wilhelmsii essential oils against APAP induced hepatic injuries.
PMID- 28510974
TI - Differentiation between two strains of microalga Parachlorella kessleri using
modern spectroscopic method.
AB - BACKGROUND: The differentiation between wild type of Parachlorella kessleri and
its mutant strains PC Mut2, PC Mut4 by using the Multi-functional Plant
Efficiency Analyzer (M-REA-2) was studied. Mutant algal cells of P. kessleri have
been obtained by UV-C during 3 and 10 min respectively. RESULTS: Light-induced
kinetics of prompt fluorescence (OJIP transients), delayed fluorescence and
modulated reflection at 820 nm (redox transitions of P700 in PSI) showed
disturbance of electron transport flow in photosystem II (PSII) and an increase
fraction of non-reducing centers of secondary quinone acceptors of electron (QB).
In addition, the amplitudes of the fast and slow peak in the kinetics of the
delayed light emission and non-photochemical fluorescence quenching ( NPQ) were
significantly reduced in mutant cells, indicating low level of the membrane
energization of photosynthetic membranes. Changes of photosynthetic reactions of
mutants may lead to an increase of the carotenoids content, which protect cells
against the light stress. CONCLUSION: It is suggested to use parameters of
induction curves of prompt and delayed fluorescence to characterize mutant algal
cells in biotechnological studies.
PMID- 28510975
TI - In vitro propagation of Gentiana scabra Bunge - an important medicinal plant in
the Chinese system of medicines.
AB - BACKGROUND: Gentiana scabra Bunge commonly known as 'Long dan cao' in China has
been used in traditional Chinese medicines for more than 2000 years. Dry roots
and rhizome of the herb have been used for the treatment of inflammation,
anorexia, indigestion and gastric infections. Iridoids and secoiridoids are the
main bioactive compounds which attribute to the pharmacological properties of
this plant. The species is difficult to mass propagate by seed due to the low
percentage of germination and limited dormancy period. Wild populations in some
locations are considered to be in the endangered category due to over
exploitation. RESULTS: In the present study, we report an efficient
micropropagation system. Shoot apices of six weeks old in vitro grown G. scabra
plants were used as explants for the in vitro propagation. Induction of multiple
shoots (9.1/explant) was achieved on the culture of shoot apices on half strength
Murashige and Skoog's basal medium (MSBM) containing 2.0 mg/L-1 6
benzylaminopurine (BA), 3% sucrose and 0.9% Difco agar. In vitro shoots induced
profuse rooting on half strength of MSBM supplemented with 0.1 mg/L-1 1
naphthaleneacetic acid (NAA), 3% sucrose and 0.3% gelrite. A two-stage
ventilation closure procedure during the in vitro culture, and transparent sachet
technique enhanced the survival rate of G. scabra plantlets to 96% in the
greenhouse. Tissue culture plants flowered after 5 months of transfer to pots.
CONCLUSIONS: A simple and an efficient in vitro propagation protocol of Gentiana
scabra Bunge by optimizing the medium composition and ventilation closure
treatments has been developed. The protocol can be very useful in germplasm
conservation and commercial cultivation of G. scabra plants.
PMID- 28510976
TI - Effects of salt stress on antioxidant defense system in the root of Kandelia
candel.
AB - BACKGROUND: This study aimed to explore the active oxygen scavenging mechanism of
Kandelia candel, in order to provide a theoretical basis for further analysis on
the physiological mechanism of salt tolerance in mangrove plants. Different
concentrations of NaCl solution (0, 150, 300 and 450 mmol/L) were used for salt
stress treatments on Kandelia candel, physiological indicators in the root of
Kandelia candel were measured in different processing time. RESULTS: With the
increase of salt concentrations and processing time, the contents of total
proteins in the root of Kandelia candel were reduced; the CAT activity, SOD
activity, ASA content and MDA content all had decreased with the increase of salt
concentrations and shown a trend from ascent to descent with the increase of
processing time, the peak of ASA and MDA contents were observed at 6 h, that of
SOD activity was observed at 9 h and that of CAT activity was at 12 h; POD
activity had shown an overall upward trend with the increase of salt
concentrations and processing time, which reached the maximum at 24 h; the
variations of these physiological indicators were more significant in high
concentrations of NaCl solution (450 mmol/L). CONCLUSIONS: A certain salt
concentration (<300 mmol/L) was required for the growth of Kandelia candel
seedlings. At the early stage of high-salt stress, Kandelia candel can rapidly
activate antioxidant defense system to resist the salt induced oxidative stress,
thus reducing the damages of oxidative stress to plasma membrane, which might be
an effective means for Kandelia candel to resist high salt stress.
PMID- 28510978
TI - Overexpression of a SNARE protein AtBS14b alters BR response in Arabidopsis.
AB - BACKGROUND: N-ethyl-maleimide sensitive factor adaptor protein receptor (SNAREs)
domain-containing proteins were known as key players in vesicle-associated
membrane fusion. Genetic screening has revealed the function of SNAREs in
different aspects of plant biology, but the role of many SNAREs are still
unknown. In this study, we have characterized the role of Arabidopsis Qc-SNARE
protein AtBS14b in brassinosteroids (BRs) signaling pathway. RESULTS: AtBS14b
overexpression (AtBS14b ox) plants exhibited short hypocotyl and petioles lengths
as well as insensitivity to exogenously supplied BR, while AtBS14b mutants did
not show any visible BR-dependent morphological differences. BR biosynthesis
enzyme BR6OX2 expression was slightly lower in AtBS14b ox than in wild type
plants. Further BR-mediated repression of BR6OX2, CPD and DWF4 was inhibited in
AtBS14b ox plants. AtBS14b-mCherry fusion protein localized in vesicular
compartments surrounding plasma membrane in N. benthamiana leaves. In addition,
isolation of AtBS14b-interacting BR signaling protein, which localized in plasma
membrane, showed that AtBS14b directly interacted with membrane steroid binding
protein 1 (MSBP1), but did not interact with BAK1 or BRI1. CONCLUSION: These data
suggested that Qc-SNARE protein AtBS14b is the first SNARE protein identified
that interacts with MSBP1, and the overexpression of AtBS14b modulates BR
response in Arabidopsis.
PMID- 28510977
TI - Exogenous spermidine-induced changes at physiological and biochemical parameters
levels in tomato seedling grown in saline-alkaline condition.
AB - BACKGROUND: Tomato is one of the most popular vegetables, and middle tolerance
for salt stress. Spermidine (Spd) has an important role in plant defense
mechanisms against abiotic stress; however, relatively few data are available
regarding Spd in responses of tomato to saline-alkaline stress. The effect of
0.25 mmol/L Spd on some physiological parameters of two tomato cultivars grown in
75 mmol/L saline-alkaline solutions were studied. Two cultivars are cv. Jinpeng
chaoguan which is a highly salt-tolerant ecotype and cv. Zhongza No. 9 which is
more salt-sensitive ecotype. RESULTS: Saline-alkaline stress upset nitrogen
metabolism, induced the antioxidant enzyme activities, and accumulated much more
reactive oxygen species (ROS) and osmoregulation substances in two tomato
cultivars leaves. Under saline-alkaline stress condition, Spd-treated seedlings
accumulated more osmoregulation substances and had greater activities of
antioxidative enzymes. Exogenous Spd counteracted the stress-induced increase of
contents of malondialdehyde and ammonium, glutamate dehydrogenase activity, and
decreased in nitrate, nitrate reductase, nitrite reductase, glutamine synthetase,
glutamate synthase, glutamate oxaloacetate transaminase, and glutamate pyruvate
transaminase activities. Additionally, the effect of Spd was more significantly
in salt-sensitive cultivar 'Zhongza No. 9'. CONCLUSIONS: Overall, exogenous
spermidine can attenuate negative effects of saline-alkaline stress on tomato
seedlings which effects may depend on the plant species, and even cultivars.
PMID- 28510979
TI - Isolation and identification of a phytotoxic substance from the emergent
macrophyte Centrostachys aquatica.
AB - BACKGROUND: Centrostachys aquatica is a perennial emergent macrophyte in marshy
places and in rivers. The species was recorded in Senegal and Nigeria, but
widespread in tropical Africa, and South and East Asia. Aqueous methanol extracts
C. aquatica was found to be toxic to several plant species. However, no
phytotoxic substance has been reported in this species. Therefore, we
investigated phytotoxic activity and searched for phytotoxic substances with
allelopathic activity in C. aquatica. RESULTS: An aqueous methanol extract of C.
aquatica inhibited the growth of roots and hypocotyls of cress (Lepidium
sativum). The extract was then purified by several chromatographic runs and a
phytotoxic substance with allelopathic activity was isolated and identified by
spectral analysis as loliolide. Loliolide inhibited cress root and hypocotyl
growth at concentrations greater than 0.03 MUM. The concentrations required for
50% growth inhibition of cress roots and hypocotyls was 0.18 and 0.15 MUM,
respectively. CONCLUSION: These results suggest that loliolide is a phytotoxic
substance and may contribute to the allelopathic effect caused by C. aquatica.
PMID- 28510980
TI - Begonia jinyunensis (Begoniaceae, section Platycentrum), a new palmately compound
leaved species from Chongqing, China.
AB - BACKGROUND: Continental China is the center of Begonia species diversity in Asia
and contains more than 60 species out of about 110 named species of section
Platycentrum. Mt. Jinyun, located in Chongqing City at the upper reaches of the
Yangtze River, harbors a subtropical broadleaved forest with high species
diversity. During a botanical survey in Mt. Jinyun, an unknown Begonia species of
sect. Platycentrum with palmately compound leaves was collected and studied based
on detailed morphological observations and cytological and molecular phylogenetic
analyses. RESULTS: The unknown Begonia bears a superficial resemblance to B.
hemsleyana in having palmately compound leaves, a feature unseen in other species
of sect. Platycentrum in China. It is however sharply distinct from the latter in
the acaulous habit with aerial stems seen only at anthesis and long rhizomes (vs.
erect stems to 70 cm or taller with short rhizomes), 4-6 pinnatilobed leaflets
with indistinct, decurrent petiolules (vs. 7-10 serrate leaflets with distinct
petiolules), and white (vs. pink) tepals. Molecular phylogenetic analyses based
on nuclear ribosomal DNA and chloroplast DNA sequences indicated that this
species was allied to Platycentrum species occurring in Southwest and South
central China and Vietnam, including B. hemsleyana, and clearly separable from
these species. Somatic chromosome number of 2n = 22 was reported for this unknown
species. The diploid chromosome number is agreeable with those published for
Begonia sect. Platycentrum. CONCLUSIONS: The unknown Begonia is confirmed to be a
new species of sect. Platycentrum and hereto described as Begonia jinyunensis C.
I Peng, B. Ding & Q. Wang.
PMID- 28510981
TI - Effect of phosphorus deficiency on photosynthetic inorganic carbon assimilation
of three climber plant species.
AB - BACKGROUND: P deficiency in karst areas significantly influenced leaf
photosynthesis and carbon metabolisms in plants which were bad for plant growth.
Meanwhile, fertilizer application would cause lots of environmental problems.
Therefore planning and developing P deficiency-resistant plants in karst areas
are important to prevent shortage of P resources and reduce the environmental
impacts of P supplementation. RESULTS: This study examined the photosynthetic
response of three climber plant species, namely, Pharbitis nil (Linn.) Choisy,
Lonicera pampaninii Levl, and Parthenocissus tricuspidata (Sieb.et Zucc.) Planch
to phosphorus (P) deficiency stress. The plants were exposed to P deficiency
stress at three treatments of 0.125 mM, 0.031 mM, and 0 mM for 30 d; 0.250 mM P
was used as the control. Photosynthetic responses were determined by measurement
of leaf photosynthesis, chlorophyll fluorescence, carbonic anhydrase activity,
and stable carbon isotope ratios. Pharbitis nil showed high CA activity, more
negative delta13C values and could maintain long-term stable photosynthetic
capacity. Lonicera pampaninii also showed high CA activity but positive delta13C
values compared to Pharbitis nil, and its photosynthetic capacity decreased as P
deficiency stress increased. Parthenocissus tricuspidata had a low photosynthesis
and positive delta13C values compared to Pharbitis nil, it could grow normally
even under 0 mM P. CONCLUSIONS: Pharbitis nil was tolerant to long-term, severe P
deficiency stress, a finding that is attributed to its stable PSII and regulation
of carbonic anhydrase. Lonicera pampaninii showed a poor adaptability to short
term P deficiency, but exhibited long-term tolerance under 0.125 mM P
concentration. Parthenocissus tricuspidata was tolerant to long-term P deficiency
stress, may exhibit a stomatal limitation. Besides, P deficiency stress had
little effect on the way of inorganic carbon utilization of the three climber
plants. Different adaptation mechanisms to P deficiency stress should be
considered for the selection of species when developing P deficiency-resistant
plants.
PMID- 28510982
TI - Immunolocalization of chromosome-associated proteins in plants - principles and
applications.
AB - The use of the immunolocalization technique combined with cytogenetic and
epigenetic studies is an indispensable tool and has contributed significantly to
the analysis of the structure and function of chromosomes, since it can provide
information about the spatial or temporal distribution of a given protein in the
nucleus and chromosomes. Several chromosome-associated proteins in plant cells
have already been identified by immunolocalization, such as histone and non
histone proteins and cell division-related protein (mitosis and meiosis). The
principle of the immunolocalization technique in plants basically involves
fixation and permeabilization of cells, the use of monoclonal or polyclonal
antibodies attached to a signaling molecule, usually a fluorochrome and detection
of the target molecule by using an epifluorescence microscope.
PMID- 28510983
TI - Effects of cadmium on lipids of almond seedlings (Prunus dulcis).
AB - BACKGROUND: Cadmium uptake and distribution, as well as its effects on lipid
composition was investigated in almond seedlings (Prunus dulcis) grown in culture
solution supplied with two concentrations of Cd (50 and 150 MUM). RESULTS: The
accumulation of Cd increased with external metal concentrations, and was
considerably higher in roots than in leaves. Fourteen days after Cd treatment,
the membrane lipids were extracted and separated on silica-gel thin layer
chromatography (TLC). Fatty acid methyl esters were analyzed by FID-GC on a
capillary column. Our results showed that Cd stress decreased the quantities of
all lipids classes (phospholipids, galactolipids and neutral lipids).
Galactolipid, phospholipid and neutral lipid concentrations decreased more in
roots than in leaves by Cd-treatment. In almost all lipid classes the proportion
of palmitic acid (16:0), linoleic (18: 2) and that of linolenic (18: 3) acid
decreased, suggesting that heavy metal treatment induced an alteration in the
fatty acid synthesis processes. CONCLUSIONS: In conclusion, our results show that
the changes found in total fatty acids, in the quantities of all lipids classes,
and in the in the profiles of individual polar lipids suggest that membrane
structure and function might be altered by Cd stress.
PMID- 28510984
TI - An active Catharanthus roseus desacetoxyvindoline-4-hydroxylase-like gene and its
transcriptional regulatory profile.
AB - BACKGROUND: Desacetoxyvindoline-4-hydroxylase is a key enzyme in the biosynthesis
of vindoline, the important intermediate leading to vinblastine and vincristine
in Catharanthus roseus. RESULTS: A d4h-like gene has been isolated from C. roseus
C20hi cells based on an EST sequence from the Suppression Subtractive
Hybridization cDNA library. The full length cDNA of d4h-like was 1427 bp encoding
372 amino acids. It had 66% identities and 80% positives with d4h at the amino
acid level. It belonged to 2-oxoglutarate dependent oxygenase superfamily as d4h
did. Real-time quantitative PCR analysis revealed that d4h-like was expressed
high in roots, flowers and C20hi cells, very low in leaves and stems. Methyl
jasmonate could significantly increase the accumulation of d4h-like transcripts.
2,4-D inhibited its expression. An approximate 2,910 bp of 5'-promoter region of
d4h-like was obtained, fused to GUS reporter gene and analyzed with fluorescence
quantitative assays using transient expression in C. roseus cell suspensions,
indicating that d4h-like promoter could drive GUS gene expression in vivo.
CONCLUSION: These results suggest that d4h-like is closely related with d4h in
the genetic evolution but with different transcriptional expression profiles. It
may be revolved in the hormone-independency of C20hi cells.
PMID- 28510985
TI - Changing diagnosis coding routines may confound the results of longitudinal
childhood pneumonia studies.
AB - AIM: This Swedish study compared the discharge diagnosis codes used for children
up to the age of five hospitalised for acute lower respiratory tract infections
before and after the introduction of the pneumococcal conjugate vaccine in 2007.
METHODS: The International Classification of Diseases-10th revision codes were
used. We compared the discharge diagnosis codes at the Astrid Lindgren Children's
Hospital from 1 July 2005 to 30 June 2007 (n=1,127) and 1 July 2011 to 30 June
2013 (n=1,240) in relation to the diagnostic methods used. RESULTS: There was a
54% reduction in the rate of all-cause pneumonia from the first to the second
period in children aged 0-1 years, but some of this could have been due to the
improved diagnosis of viral infections and us changing the code for respiratory
syncytial virus infection from pneumonia to bronchiolitis. The overall rate of
acute lower respiratory tract infections was unchanged. CONCLUSION: We could not
determine how much of the reduction in bacterial pneumonia in children under one
was because of the introduction of the pneumococcal conjugate vaccine, based
solely on discharge codes. Longitudinal register studies should take changes in
diagnosis codes into account.
PMID- 28510987
TI - Iridium-Catalyzed Formyl-Selective Deuteration of Aldehydes.
AB - We report the first direct catalytic method for formyl-selective deuterium
labeling of aromatic aldehydes under mild conditions, using an iridium-based
catalyst designed to favor formyl over aromatic C-H activation. A good range of
aromatic aldehydes is selectively labeled, and a one-pot labeling/olefination
method is also described. Computational studies support kinetic product control
over competing aromatic labeling and decarbonylation pathways.
PMID- 28510988
TI - Barriers to obstetric fistula treatment in low-income countries: a systematic
review.
AB - OBJECTIVE: To identify the barriers faced by women living with obstetric fistula
in low-income countries that prevent them from seeking care, reaching medical
centres and receiving appropriate care. METHODS: Bibliographic databases, grey
literature, journals, and network and organisation websites were searched in
English and French from June to July 2014 and again from August to November 2016
using key search terms and specific inclusion and exclusion criteria for
discussion of barriers to fistula treatment. Experts provided recommendations for
additional sources. RESULTS: Of 5829 articles screened, 139 were included in the
review. Nine groups of barriers to treatment were identified: psychosocial,
cultural, awareness, social, financial, transportation, facility shortages,
quality of care and political leadership. Interventions to address barriers
primarily focused on awareness, facility shortages, transportation, financial and
social barriers. At present, outcome data, though promising, are sparse and the
success of interventions in providing long-term alleviation of barriers is
unclear. CONCLUSION: Results from the review indicate that there are many
barriers to fistula treatment, which operate at the individual, community and
national levels. The successful treatment of obstetric fistula may thus require
targeting several barriers, including depression, stigma and shame, lack of
community-based referral mechanisms, financial cost of the procedure,
transportation difficulties, gender power imbalances, the availability of
facilities that offer fistula repair, community reintegration and the competing
priorities of political leadership.
PMID- 28510986
TI - Blood pressure normalization via pharmacotherapy improves cutaneous microvascular
function through NO-dependent and NO-independent mechanisms.
AB - : Hypertension is associated with endothelial dysfunction and vascular
remodeling. OBJECTIVE: To assess effects of antihypertensive pharmacotherapy on
eNOS- and iNOS-dependent mechanisms and maximal vasodilator capacity in the
cutaneous microvasculature. METHODS: Intradermal microdialysis fibers were placed
in 15 normotensive (SBP 111+/-2 mm Hg), 12 unmedicated hypertensive (SBP 142+/-2
mm Hg), and 12 medicated hypertensive (SBP 120+/-2 mm Hg) subjects. Treatments
were control, iNOS-inhibited (1400w), and NOS-inhibited (l-NAME). Red cell flux,
measured during local heating (42 degrees C) and ACh dose-response protocols, was
normalized to CVC (flux MAP-1 ) and a percentage of maximal vasodilation (%CVCmax
). RESULTS: Compared to normotensives, ACh-mediated vasodilation was attenuated
in the hypertensive (P<.001), but not in medicated subjects (P=.83). NOS
inhibition attenuated ACh-mediated vasodilation in normotensives compared to
hypertensive (P<.001) and medicated (P<.001) subjects. With iNOS inhibition,
there was no difference in ACh-mediated vasodilation between groups. Compared to
the normotensives, local heat-induced vasodilation was attenuated in the
hypertensives (P<.001), but iNOS inhibition augmented vasodilation in the
hypertensives so this attenuation was abolished (P=.31). Compared to
normotensives, maximal vasodilator capacity was reduced in the hypertensive
(P=.014) and medicated subjects (P=.004). CONCLUSIONS: In the cutaneous
microvasculature, antihypertensive pharmacotherapy improved endothelial function
through NO-dependent and NO-independent mechanisms, but did not improve maximal
vasodilator capacity.
PMID- 28510990
TI - Perioperative nutrition management as an important component of surgical capacity
in low- and middle-income countries.
AB - Needs for surgical care are growing in low- and middle-income countries. Existing
surgical care capacity indicators, focusing on the availability of equipment,
personnel, and operation and anaesthetic skills, are not intended to evaluate
perioperative nutrition management, which influences surgical outcomes. In this
narrative review, we describe the prevalence of malnutrition and its clinical
consequences among surgical patients in low- and middle-income countries, suggest
potential measures to improve nutrition management and discuss the necessity of
considering nutrition management as a component of surgical care capacity.
PMID- 28510989
TI - Characterization of Brachyspira hyodysenteriae isolates from Italy by multilocus
sequence typing and multiple locus variable number tandem repeat analysis.
AB - AIMS: To evaluate and compare the capabilities of multilocus sequence typing
(MLST) and multiple locus variable number tandem repeat analysis (MLVA)
techniques to characterize Brachyspira hyodysenteriae isolates and to investigate
the relationship between pleuromutilin resistance and genetic variability.
METHODS AND RESULTS: MLST genotyping was performed on 180 B. hyodysenteriae
isolates, and the results were evaluated considering profiles from 108 other
strains previously reported in the database. In total, 37 sequence types were
obtained. The MLVA approach completely characterized 172 strains and grouped the
isolates into 22 different profiles. The combination of MLST and MLVA showed a
slight increase in the discriminatory power, identifying 33 joint profiles. An
antibiotic resistance analysis showed a reduction in the susceptibility to
pleuromutilins over time, and a weak association between susceptibility to
valnemulin and inclusion in clonal complex 4. CONCLUSION: MLST and MLVA are
reliable methods for characterizing B. hyodysenteriae strains and they have
comparable discriminatory power. SIGNIFICANCE AND IMPACT OF THE STUDY: The
genotyping of B. hyodysenteriae isolates and a database of all the genetic
profiles collected during the diagnostic activities could support traditional
epidemiological investigations in identifying infection sources and routes of
transmission among herds, and in developing more effective control measures.
PMID- 28510991
TI - Development of a panel of recombinase polymerase amplification assays for
detection of common bacterial urinary tract infection pathogens.
AB - AIMS: To develop and evaluate the performance of a panel of isothermal real-time
recombinase polymerase amplification (RPA) assays for detection of common
bacterial urinary tract infection (UTI) pathogens. METHODS AND RESULTS: The panel
included RPAs for Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis,
Pseudomonas aeruginosa and Enterococcus faecalis. All five RPAs required reaction
times of under 12 min to reach their lower limit of detection of 100 genomes per
reaction or less, and did not cross-react with high concentrations of nontarget
bacterial genomic DNA. In a 50-sample retrospective clinical study, the five-RPA
assay panel was found to have a specificity of 100% (95% CI, 78-100%) and a
sensitivity of 89% (95% CI, 75-96%) for UTI detection. CONCLUSIONS: The
analytical and clinical validity of RPA for the rapid and sensitive detection of
common UTI pathogens was established. SIGNIFICANCE AND IMPACT OF THE STUDY: Rapid
identification of the causative pathogens of UTIs can be valuable in preventing
serious complications by helping avoid the empirical treatment necessitated by
traditional urine culture's 48-72-h turnaround time. The routine and widespread
use of RPA to supplement or replace culture-based methods could profoundly impact
UTI management and the emergence of multidrug-resistant pathogens.
PMID- 28510993
TI - Chiral separation of quinolones by liquid chromatography and capillary
electrophoresis.
AB - The quinolones are derivatives of oxoquinolines and mostly known for their
antibacterial and antiviral activities. Many quinolones are chiral compounds
having asymmetric centers and important due to their enantioselective biological
activities. In order to study the biological activities of quinolone enantiomers,
to control the manufacturing of homochiral drugs and to prepare necessary
quantities of pure enantiomers for preclinical or clinical trials, respective
chiral separation methods are urgently needed. In this context, the present
review discusses chromatographic and electrophoretic methods for the
enantioseparation of chiral quinolones and provides some useful information on
their physical and pharmaceutical properties. The drawbacks of currently used
techniques are revealed and ways to overcome them are outlined. Moreover,
recommendations for an optimal choice of a separation protocol are given.
PMID- 28510994
TI - Improved detection of Burkholderia pseudomallei from non-blood clinical specimens
using enrichment culture and PCR: narrowing diagnostic gap in resource
constrained settings.
AB - OBJECTIVES: To evaluate the diagnostic utility of enrichment culture and PCR for
improved case detection rates of non-bacteraemic form of melioidosis in limited
resource settings. METHODS: Clinical specimens (n = 525) obtained from patients
presenting at a tertiary care hospital of South India with clinical symptoms
suggestive of community-acquired pneumonia, lower respiratory tract infections,
superficial or internal abscesses, chronic skin ulcers and bone or joint
infections were tested for the presence of Burkholderia pseudomallei using
conventional culture (CC), enrichment culture (EC) and PCR. Sensitivity,
specificity, positive and negative predictive values of CC and PCR were initially
deduced using EC as the gold standard method. Further, diagnostic accuracies of
all the three methods were analysed using Bayesian latent class modelling (BLCM).
RESULTS: Detection rates of B. pseudomallei using CC, EC and PCR were 3.8%, 5.3%
and 6%, respectively. Diagnostic sensitivities and specificities of CC and PCR
were 71.4, 98.4% and 100 and 99.4%, respectively in comparison with EC as the
gold standard test. With Bayesian latent class modelling, EC and PCR demonstrated
sensitivities of 98.7 and 99.3%, respectively, while CC showed a sensitivity of
70.3% for detection of B. pseudomallei. An increase of 1.6% (95% CI: 1.08-4.32%)
in the case detection rate of melioidosis was observed in the study population
when EC and/or PCR were used in adjunct to the conventional culture technique.
CONCLUSIONS: Our study findings underscore the diagnostic superiority of
enrichment culture and/or PCR over conventional microbiological culture for
improved case detection of melioidosis from non-blood clinical specimens.
PMID- 28510992
TI - Lymph node effective vascular permeability and chemotherapy uptake.
AB - OBJECTIVE: Lymph node metastases are a poor prognostic factor. Additionally,
responses of lymph node metastasis to therapy can be different from the primary
tumor. Investigating the physiologic lymph node blood vasculature might give
insight into the ability of systemic drugs to penetrate the lymph node, and thus
into the differential effect of therapy between lymph node metastasis and primary
tumors. Here, we measured effective vascular permeability of lymph node blood
vessels and attempted to increase chemotherapy penetration by increasing
effective vascular permeability. METHODS: We developed a novel three-dimensional
method to measure effective vascular permeability in murine lymph nodes in vivo.
VEGF-A was systemically administered to increase effective vascular permeability.
Validated high-performance liquid chromatography protocols were used to measure
chemotherapeutic drug concentrations in untreated and VEGF-A-treated lymph nodes,
liver, spleen, brain, and blood. RESULTS: VEGF-A-treated lymph node blood vessel
effective vascular permeability (mean 3.83 * 10-7 cm/s) was significantly higher
than untreated lymph nodes (mean 9.87 * 10-8 cm/s). No difference was found in
lymph node drug accumulation in untreated versus VEGF-A-treated mice.
CONCLUSIONS: Lymph node effective vascular permeability can be increased
(~fourfold) by VEGF-A. However, no significant increase in chemotherapy uptake
was measured by pretreatment with VEGF-A.
PMID- 28510995
TI - Native Mass Spectrometry from Common Buffers with Salts That Mimic the
Extracellular Environment.
AB - Nonvolatile salts are essential for the structures and functions of many proteins
and protein complexes but can severely degrade performance of native mass
spectrometry by adducting to protein and protein complex ions, thereby reducing
sensitivity and mass measuring accuracy. Small nanoelectrospray emitters are used
to form protein and protein complex ions directly from high-ionic-strength (>150
mm) nonvolatile buffers with salts that mimic the extracellular environment.
Charge-state distributions are not obtained for proteins and protein complexes
from six commonly used nonvolatile buffers and >=150 mm Na+ with conventionally
sized nanoelectrospray emitter tips but are resolved with 0.5 MUm tips. This
method enables mass measurements of proteins and protein complexes directly from
a variety of commonly used buffers with high concentrations of nonvolatile salts
and eliminates the need to buffer exchange into volatile ammonium buffers
traditionally used in native mass spectrometry.
PMID- 28510996
TI - Tramadol with or without paracetamol (acetaminophen) for cancer pain.
AB - BACKGROUND: Tramadol is an opioid analgesic licensed for use in moderate to
severe pain. It is considered as a low risk for abuse, so control regulations are
not as stringent as for 'strong' opioids such as morphine. It has a potential
role as a step 2 option of the World Health Organization (WHO) analgesic ladder.
OBJECTIVES: To assess the benefits and adverse effects of tramadol with or
without paracetamol (acetaminophen) for cancer-related pain. SEARCH METHODS: We
searched the following databases using a wide range of search terms: the Cochrane
Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and LILACS. We
also searched three clinical trials registry databases. The date of the last
search was 2 November 2016. SELECTION CRITERIA: We selected studies that were
randomised, with placebo or active controls, or both, and included a minimum of
10 participants per treatment arm. We were interested particularly in blinded
studies, but also included open studies.We excluded non-randomised studies,
studies of experimental pain, case reports, and clinical observations. DATA
COLLECTION AND ANALYSIS: Two review authors independently extracted data using a
standard form and checked for agreement before entry into Review Manager 5. We
included information about the number of participants treated and demographic
details, type of cancer, drug and dosing regimen, study design (placebo or active
control) and methods, study duration and follow-up, analgesic outcome measures
and results, withdrawals, and adverse events. We collated multiple reports of the
same study, so that each study, rather than each report, was the unit of interest
in the review. We assessed the evidence using GRADE and created a 'Summary of
findings' table.The main outcomes of interest for benefit were pain reduction of
30% or greater and 50% or greater from baseline, participants with pain no worse
than mild, and participants feeling much improved or very much improved. MAIN
RESULTS: We included 10 studies (12 reports) with 958 adult participants. All the
studies enrolled participants with chronic malignant tumour-related pain who were
experiencing pain intensities described as moderate to severe, with most
experiencing at least 4/10 with current treatment. The mean ages were 59 to 70
years, with participants aged between 24 and 87 years. Study length ranged from
one day to six months. Five studies used a cross-over design. Tramadol doses
ranged from 50 mg as single dose to 600 mg per day; doses of 300 mg per day to
400 mg per day were most common.Nine studies were at high risk of bias for one to
four criteria (only one high risk of bias for size). We judged all the results to
be very low quality evidence because of widespread lack of blinding of outcome
assessment, inadequately described sequence generation, allocation concealment,
and small numbers of participants and events. Important outcomes were poorly
reported. There were eight different active comparators and one comparison with
placebo. There was little information available for any comparison and no firm
conclusions could be drawn for any outcome.Single comparisons of oral tramadol
with codeine plus paracetamol, of dihydrocodeine, and of rectal versus oral
tramadol provided no data for key outcomes. One study used tramadol combined with
paracetamol; four participants received this intervention. One study compared
tramadol with flupirtine - a drug that is no longer available. One study compared
tramadol with placebo and a combination of cobrotoxin, tramadol, and ibuprofen,
but the dosing schedule poorly explained.Two studies (191 participants) compared
tramadol with buprenorphine. One study (131 participants) reported a similar
proportion of no or mild pain at 14 days.Three studies (300 participants)
compared tramadol with morphine. Only one study, combining tramadol, tramadol
plus paracetamol, and paracetamol plus codeine as a single weak-opioid group
reported results. Weak opioid produced reduction in pain of at least 30% from
baseline in 55/117 (47%) participants, compared with 91/110 (82%) participants
with morphine. Weak opioid produced reduction in pain of at least 50% in 49/117
(42%) participants, compared with 83/110 (75%) participants with morphine.There
was no useful information for any other outcome of benefit or harm. AUTHORS'
CONCLUSIONS: There is limited, very low quality, evidence from randomised
controlled trials that tramadol produced pain relief in some adults with pain due
to cancer and no evidence at all for children. There is very low quality evidence
that it is not as effective as morphine. This review does not provide a reliable
indication of the likely effect. The likelihood that the effect will be
substantially different is very high. The place of tramadol in managing cancer
pain and its role as step 2 of the WHO analgesic ladder is unclear.
PMID- 28510997
TI - Impact of m-health application used by community health volunteers on improving
utilisation of maternal, new-born and child health care services in a rural area
of Uttar Pradesh, India.
AB - OBJECTIVE: To raise the quality of counselling by community health volunteers
resulting in improved uptake of maternal, neonatal and child health services
(MNCH), an m-health application was introduced under a project named 'Reducing
Maternal and Newborn Deaths (ReMiND)' in district Kaushambi in India. We report
the impact of this project on coverage of key MNCH services. METHODS: A pre- and
post-quasi-experimental design was undertaken to assess the impact of
intervention. This project was introduced in two community development blocks in
Kaushambi district in 2012. Two other blocks from the same district were selected
as controls after matching for coverage of two indicators at baseline - antenatal
care and institutional deliveries. The Annual Health Survey conducted by the
Ministry of Health and Family Welfare in 2011 served as pre-intervention data,
whereas a household survey in four blocks of Kaushambi district in 2015 provided
post-intervention coverage of key services. Propensity score matched samples from
intervention and control areas in pre-intervention and post-intervention periods
were analysed using difference-in-difference method to estimate the impact of
ReMiND project. RESULTS: We found a statistically significant increase in
coverage of iron-folic acid supplementation (12.58%), self-reporting of
complication during pregnancy (13.11%) and after delivery (19.6%) in the
intervention area. The coverage of three or more antenatal care visits, tetanus
toxoid vaccination, full antenatal care and ambulance usage increased in
intervention area by 10.3%, 4.28%, 1.1% and 2.06%, respectively; however, the
changes were statistically insignificant. CONCLUSION: Three of eight services
which were targeted for improvement under ReMiND project registered a significant
improvement as result of m-health intervention.
PMID- 28510999
TI - NGWA News.
PMID- 28510998
TI - New-onset type 2 diabetes mellitus among patients receiving HIV care at Newlands
Clinic, Harare, Zimbabwe: retrospective cohort analysis.
AB - OBJECTIVE: To assess the incidence and associated factors of Type 2 Diabetes
Mellitus (T2DM) among people living with HIV (PLHIV) in Zimbabwe. METHODS: We
analysed data of all HIV-infected patients older than 16 years who attended
Newlands Clinic between March 1, 2004 and April 29, 2015. The clinic considers
patients whose random blood sugar is higher than 11.1 mmol/l and which is
confirmed by a fasting blood sugar higher than 7.0 mmol/l to have T2DM. T2DM is
also diagnosed in symptomatic patients who have a RBS >11.0 mmol/l. Risk factors
for developing T2DM were identified using Cox proportional hazard models adjusted
for confounding. Missing baseline BMI data were multiply imputed. Results are
presented as adjusted hazard ratios (aHR) with 95% confidence intervals (95% CI).
RESULTS: Data for 4,110 participants were included: 67.2% were women; median age
was 37 (IQR: 31-43) years. Median baseline CD4 count was 197 (IQR: 95-337)
cells/mm3 . The proportion of participants with hypertension at baseline was
15.5% (n=638). Over a median follow-up time of 4.7 (IQR: 2.1-7.2) years, 57
patients developed T2DM; the overall incidence rate was 2.8 (95% CI: 2.1-3.6) per
1000 person-years of follow-up. Exposure to PIs was associated with T2DM (HR:
1.80, 95% CI: 1.04-3.09). In the multivariable analysis, obesity (BMI>30 kg/m2 )
(aHR=2.26, 95% CI: 1.17-4.36), age >40 years (aHR=2.16, 95% CI: 1.22-3.83) and
male gender, (aHR=2.13, 95% CI: 1.22-3.72) were independently associated with the
risk of T2DM. HIV-related factors (baseline CD4 cell count and baseline WHO
clinical stage) were not independent risk factors for developing T2DM.
CONCLUSION: Although the incidence of T2DM in this HIV cohort was lower than that
has been observed in others, our results show that risk factors for developing
T2DM among HIV-infected people are similar to those of the general population.
HIV-infected patients in sub-Saharan Africa need a comprehensive approach to care
that includes better health services for prevention, early detection and
treatment of chronic diseases especially among the elderly and obese.
PMID- 28511000
TI - Superconducting Ferromagnetic Nanodiamond.
AB - Superconductivity and ferromagnetism are two mutually antagonistic states in
condensed matter. Research on the interplay between these two competing orderings
sheds light not only on the cause of various quantum phenomena in strongly
correlated systems but also on the general mechanism of superconductivity. Here
we report on the observation of the electronic entanglement between
superconducting and ferromagnetic states in hydrogenated boron-doped nanodiamond
films, which have a superconducting transition temperature Tc ~ 3 K and a Curie
temperature TCurie > 400 K. In spite of the high TCurie, our nanodiamond films
demonstrate a decrease in the temperature dependence of magnetization below 100
K, in correspondence to an increase in the temperature dependence of resistivity.
These anomalous magnetic and electrical transport properties reveal the presence
of an intriguing precursor phase, in which spin fluctuations intervene as a
result of the interplay between the two antagonistic states. Furthermore, the
observations of high-temperature ferromagnetism, giant positive
magnetoresistance, and anomalous Hall effect bring attention to the potential
applications of our superconducting ferromagnetic nanodiamond films in
magnetoelectronics, spintronics, and magnetic field sensing.
PMID- 28511001
TI - Monolayer Solid-State Electrolyte for Electric Double Layer Gating of Graphene
Field-Effect Transistors.
AB - The electrostatic gating of graphene field-effect transistors is demonstrated
using a monolayer electrolyte. The electrolyte, cobalt crown ether phthalocyanine
(CoCrPc) and LiClO4, is deposited as a monolayer on the graphene channel,
essentially creating an additional two-dimensional layer on top of graphene. The
crown ethers on the CoCrPc solvate lithium ions and the ion location is modulated
by a backgate without requiring liquid solvent. Ions dope the channel by inducing
image charges; the doping level (i.e., induced charge density) can be modulated
by the backgate bias with the extent of the surface potential change being
controlled by the magnitude and polarity of the backgate bias. With a crown ether
to Li+ ratio of 5:1, programming tests for which the backgate is held at -VBG
shift the Dirac point by ~15 V, corresponding to a sheet carrier density on the
order of 1012 cm-2. This charge carrier density agrees with the packing density
of monolayer CoCrPc on graphene that would be expected with one Li+ for every
five crown ethers (at the maximum possible Li+ concentration, 1013 cm-2 is
predicted). The crown ethers provide two stable states for the Li+: one near the
graphene channel (low-resistance state) and one ~5 A away from the channel (high
resistance state). Initial state retention measurements indicate that the two
states can be maintained for at least 30 min (maximum time monitored), which is
106 times longer than polymer-based electrolytes at room temperature, with at
least a 250 Omega MUm difference between the channel resistance in the high- and
low-resistance states.
PMID- 28511002
TI - Exploring High-Performance n-Type Thermoelectric Composites Using Amino
Substituted Rylene Dimides and Carbon Nanotubes.
AB - Taking advantage of the high electrical conductivity of a single-walled carbon
nanotube (SWCNT) and the large Seebeck coefficient of rylene diimide, a
convenient strategy is proposed to achieve high-performance n-type thermoelectric
(TE) composites containing a SWCNT and amino-substituted perylene diimide (PDINE)
or naphthalene diimide (NDINE). The obtained n-type composites display greatly
enhanced TE performance with maximum power factors of 112 +/- 8 (PDINE/SWCNT) and
135 +/- 14 (NDINE/SWCNT) MUW m-1 K-2. A short doping time of 0.5 h can ensure
high TE performance. The corresponding TE module consisting of five p-n junctions
reaches a large output power of 3.3 MUW under a 50 degrees C temperature
gradient. In addition, the n-type composites exhibit high air stability and
excellent thermal stability. This design strategy benefits the future fabricating
of high-performance n-type TE materials and devices.
PMID- 28511003
TI - Functionalized Graphene Enables Highly Efficient Solar Thermal Steam Generation.
AB - The ability to efficiently utilize solar thermal energy to enable liquid-to-vapor
phase transition has great technological implications for a wide variety of
applications, such as water treatment and chemical fractionation. Here, we
demonstrate that functionalizing graphene using hydrophilic groups can greatly
enhance the solar thermal steam generation efficiency. Our results show that
specially functionalized graphene can improve the overall solar-to-vapor
efficiency from 38% to 48% at one sun conditions compared to chemically reduced
graphene oxide. Our experiments show that such an improvement is a surface effect
mainly attributed to the more hydrophilic feature of functionalized graphene,
which influences the water meniscus profile at the vapor-liquid interface due to
capillary effect. This will lead to thinner water films close to the three-phase
contact line, where the water surface temperature is higher since the resistance
of thinner water film is smaller, leading to more efficient evaporation. This
strategy of functionalizing graphene to make it more hydrophilic can be
potentially integrated with the existing macroscopic heat isolation strategies to
further improve the overall solar-to-vapor conversion efficiency.
PMID- 28511004
TI - Lithium Batteries with Nearly Maximum Metal Storage.
AB - The drive for significant advancement in battery capacity and energy density
inspired a revisit to the use of Li metal anodes. We report the use of a seamless
graphene-carbon nanotube (GCNT) electrode to reversibly store Li metal with
complete dendrite formation suppression. The GCNT-Li capacity of 3351 mAh g-1GCNT
Li approaches that of bare Li metal (3861 mAh g-1Li), indicating the low
contributing mass of GCNT, while yielding a practical areal capacity up to 4 mAh
cm-2 and cycle stability. A full battery based on GCNT-Li/sulfurized carbon (SC)
is demonstrated with high energy density (752 Wh kg-1 total electrodes, where
total electrodes = GCNT-Li + SC + binder), high areal capacity (2 mAh cm-2), and
cyclability (80% retention at >500 cycles) and is free of Li polysulfides and
dendrites that would cause severe capacity fade.
PMID- 28511005
TI - Characterization of l-Theanine Excitatory Actions on Hippocampal Neurons: Toward
the Generation of Novel N-Methyl-d-aspartate Receptor Modulators Based on Its
Backbone.
AB - l-Theanine (or l-gamma-N-ethyl-glutamine) is the major amino acid found in
Camellia sinensis. It has received much attention because of its pleiotropic
physiological and pharmacological activities leading to health benefits in
humans, especially. We describe here a new, easy, efficient, and environmentally
friendly chemical synthesis of l-theanine and l-gamma-N-propyl-Gln and their
corresponding d-isomers. l-Theanine, and its derivatives obtained so far,
exhibited partial coagonistic action at N-methyl-d-aspartate (NMDA) receptors,
with no detectable agonist effect at other glutamate receptors, on cultured
hippocampal neurons. This activity was retained on NMDA receptors expressed in
Xenopus oocytes. In addition, both GluN2A and GluN2B containing NMDA receptors
were equally modulated by l-theanine. The stereochemical change from l-theanine
to d-theanine along with the substitution of the ethyl for a propyl moiety in the
gamma-N position of l- and d-theanine significantly enhanced the biological
efficacy, as measured on cultured hippocampal neurons. l-Theanine structure thus
represents an interesting backbone to develop novel NMDA receptor modulators.
PMID- 28511007
TI - Thicker Lamellae and Higher Crystallinity of Poly(lactic acid) via Applying Shear
Flow and Pressure and Adding Poly(ethylene Glycol).
AB - In this work, we explored the crystallization of poly(lactic acid) (PLA) blended
with poly(ethylene glycol) (PEG) under two inevitable processing fields (i.e.,
flow and pressure) that coexist in almost all processing for the first time.
Here, the PEG was incorporated into PLA as a molecular chain activity promoter to
induce PLA crystallization. A homemade pressuring and shearing device was
utilized to prepare samples and necessary characterization methods, such as
differential scanning calorimetry, scanning electron microscopy, and synchrotron
radiation, and were used to investigated the joint effects of PEG, pressure, and
shear flow on the crystallization behaviors and morphologies of PLA/PEG samples.
The results reveal that adding 3-5 wt % PEG into PLA can significantly increase
the PLA crystallinity due to the efficient plasticization effect of PEG, while
the PEG content reaches 10 wt %, the PLA crystallinity decreases drastically as
the phase separation between PEG and PLA occurs. We also find that applying a
higher pressure (~100 MPa) can facilitate the formation of thicker lamellae with
fewer defects as well as higher crystallinity under an equal degree of
supercooling compared to normal pressure or a low pressure condition because the
slip of molecular chains during crystallization makes the lamellae thicker under
higher pressures. The PLA crystalline structure in the PLA/PEG sample is not
influenced by the shear flow, yet the crystallinity is largely enhanced by
applying a shear flow with an appropriate intensity (0-3.5 s-1). It is worth
noting that pressure and shear flow show a synergetic effect to fabricate PLA/PEG
samples with high crystallinity. These meaningful results could beyond doubt help
comprehend the relationship between crystallization conditions and
crystallization behaviors of PLA/PEG samples and thus provide guidance to obtain
high-performance PLA/PEG products via controlling crystallization conditions.
PMID- 28511006
TI - Novel Focused Ultrasound Gene Therapy Approach Noninvasively Restores
Dopaminergic Neuron Function in a Rat Parkinson's Disease Model.
AB - Therapies capable of decelerating, or perhaps even halting, neurodegeneration in
Parkinson's disease (PD) remain elusive. Clinical trials of PD gene therapy
testing the delivery of neurotrophic factors, such as the glial cell-line derived
neurotrophic factor (GDNF), have been largely ineffective due to poor vector
distribution throughout the diseased regions in the brain. In addition, current
delivery strategies involve invasive procedures that obviate the inclusion of
early stage patients who are most likely to benefit from GDNF-based gene therapy.
Here, we introduce a two-pronged treatment strategy, composed of MR image-guided
focused ultrasound (FUS) and brain-penetrating nanoparticles (BPN), that provides
widespread but targeted GDNF transgene expression in the brain following systemic
administration. MR image-guided FUS allows circulating gene vectors to partition
into the brain tissue by noninvasive and transient opening of the blood-brain
barrier (BBB) within the areas where FUS is applied. Once beyond the BBB, BPN
provide widespread and uniform GDNF expression throughout the targeted brain
tissue. After only a single treatment, our strategy led to therapeutically
relevant levels of GDNF protein content in the FUS-targeted regions in the
striatum of the 6-OHDA-induced rat model of PD, which lasted at least up to 10
weeks. Importantly, our strategy restored both dopamine levels and dopaminergic
neuron density and reversed behavioral indicators of PD-associated motor
dysfunction with no evidence of local or systemic toxicity. Our combinatorial
approach overcomes limitations of current delivery strategies, thereby
potentially providing a novel means to treat PD.
PMID- 28511008
TI - Cascade Reaction-Based, Near-Infrared Multiphoton Fluorescent Probe for the
Selective Detection of Cysteine.
AB - The ability to detect and visualize cellular events and their associated target
biological analytes through use of cell-permeable profluorogenic probes is
dependent on the availability of activatable probes that respond rapidly and
selectively to target analytes by production of fluorescent reporting molecules
whose excitation and emission energies span a broad range. Herein is described a
new probe, DCM-Cys, that preferentially reacts with cysteine to form a
dicyanomethylene-4H-pyran (DCM) reporter whose red-energy fluorescence can be
stimulated by two-photon, near-infrared excitation so as to provide visualization
of cysteine presence inside living human cells with a high signal-to-background
ratio. These aforementioned characteristics and the ability of DCM-Cys to provide
selective, nanomolar-level in vitro cysteine detection, as demonstrated by its
lack of significant response to other thiols and potential interfering agents
from biological environments, are attributed to the molecular designs of the DCM
Cys probe and DCM reporter. Attachment of an acryl moiety to the DCM reporter via
a self-eliminating, electron-withdrawing benzyl alcohol-carbamate linker offers a
probe having selective, sensitive reaction with cysteine to rapidly produce a
reporter whose energies of excitation and emission (lambdaabsreport = 480 nm,
lambdaemisreport = 640 nm) are red-shifted from those of the DCM-Cys probe
(lambdaabsprobe = 440 nm, lambdaemisprobe = 550 nm), thereby leading to low
background signal from abundant probe and a large signal from the resulting
reporter of cysteine presence.
PMID- 28511010
TI - pi-Extended and Curved Antiaromatic Polycyclic Hydrocarbons.
AB - Synthesis of antiaromatic polycyclic hydrocarbons (PHs) is challenging because
the high energy of their highest occupied molecular orbital and low energy of
their lowest unoccupied molecular orbital cause them to be reactive and unstable.
In this work, two large antiaromatic acene analogues, namely,
cyclopenta[pqr]indeno[2,1,7-ijk]tetraphene (CIT, 1a) and
cyclopenta[pqr]indeno[7,1,2-cde]picene (CIP, 1b), as well as a curved
antiaromatic molecule with 48 pi-electrons, dibenzo[a,c]diindeno[7,1,2
fgh:7',1',2'-mno]phenanthro[9,10-k]tetraphene (DPT, 1c), are synthesized on the
basis of the corona of indeno[1,2-b]fluorene. These three antiaromatic PHs
possess a narrow energy gap down to 1.55 eV and exhibit high kinetic stability
under ambient conditions. Moreover, these compounds display reversible electron
transfer processes in both the cathodic and anodic regimes. Their cation and
anion radicals are characterized by in situ vis-NIR absorption and electron
paramagnetic resonance spectroelectrochemistry. The X-ray crystallographic
analysis confirms that while CIP and CIT manifest planar structures, DPT shows a
curved pi-conjugated carbon skeleton. The synthetic strategy starting from ortho
substituted benzene units to construct five-membered rings in this work provides
a unique entry to novel pentagon-embedding or curved antiaromatic polycyclic
hydrocarbons. In addition, besides the detailed chemical and physical
investigations, microscale single-crystal fiber field-effect transistors were
also fabricated.
PMID- 28511009
TI - The Development of Target-Specific Pose Filter Ensembles To Boost Ligand
Enrichment for Structure-Based Virtual Screening.
AB - Structure-based virtual screening (SBVS) has become an indispensable technique
for hit identification at the early stage of drug discovery. However, the
accuracy of current scoring functions is not high enough to confer success to
every target and thus remains to be improved. Previously, we had developed binary
pose filters (PFs) using knowledge derived from the protein-ligand interface of a
single X-ray structure of a specific target. This novel approach had been
validated as an effective way to improve ligand enrichment. Continuing from it,
in the present work we attempted to incorporate knowledge collected from diverse
protein-ligand interfaces of multiple crystal structures of the same target to
build PF ensembles (PFEs). Toward this end, we first constructed a comprehensive
data set to meet the requirements of ensemble modeling and validation. This set
contains 10 diverse targets, 118 well-prepared X-ray structures of protein-ligand
complexes, and large benchmarking actives/decoys sets. Notably, we designed a
unique workflow of two-layer classifiers based on the concept of ensemble
learning and applied it to the construction of PFEs for all of the targets.
Through extensive benchmarking studies, we demonstrated that (1) coupling PFE
with Chemgauss4 significantly improves the early enrichment of Chemgauss4 itself
and (2) PFEs show greater consistency in boosting early enrichment and larger
overall enrichment than our prior PFs. In addition, we analyzed the pairwise
topological similarities among cognate ligands used to construct PFEs and found
that it is the higher chemical diversity of the cognate ligands that leads to the
improved performance of PFEs. Taken together, the results so far prove that the
incorporation of knowledge from diverse protein-ligand interfaces by ensemble
modeling is able to enhance the screening competence of SBVS scoring functions.
PMID- 28511011
TI - Iron Hydroperoxide Intermediate in Superoxide Reductase: Protonation or
Dissociation First? MM Dynamics and QM/MM Metadynamics Study.
AB - Superoxide reductase is a mononuclear iron enzyme involved in superoxide radical
detoxification in some bacteria. Its catalytic mechanism is associated with the
remarkable formation of a ferric hydroperoxide Fe3+-OOH intermediate, which is
specifically protonated on its proximal oxygen to generate the reaction product
H2O2. Here, we present a computational study of the protonation mechanism of the
Fe3+-OOH intermediate, at different levels of theory. This was performed on the
whole system (solvated protein) using well-tempered metadynamics at the QM/MM
(B3LYP/AmberFF99SB) level. Enabled by the development of a new set of force field
parameters for the active site, a conformational MM study of the Fe3+-OOH species
gave insights into its solvation pattern, in addition to generating the two
starting conformations for the ab initio metadynamics setup. Two different
protonation mechanisms for the Fe3+-OOH intermediate have been found depending on
the starting structure. Whereas a possible mechanism involves at first the
protonation of the hydroperoxide ligand and then dissociation of H2O2, the most
probable one starts with an unexpected dissociation of the HOO- ligand from the
iron, followed by its protonation. This favored reactivity was specifically
linked to the influence of both the nearby conserved lysine 48 residue and the
microsolvatation on the charge distribution of the oxygens of the HOO- ligand.
These data highlight the crucial role of the whole environment, solvent, and
protein, to describe accurately this second protonation step in superoxide
reductase. This is clearly not possible with smaller models unable to reproduce
correctly the mechanistically determinant charge distribution.
PMID- 28511012
TI - Nonlinear Optical Magnetism Revealed by Second-Harmonic Generation in
Nanoantennas.
AB - Nonlinear effects at the nanoscale are usually associated with the enhancement of
electric fields in plasmonic structures. Recently emerged new platform for
nanophotonics based on high-index dielectric nanoparticles utilizes optically
induced magnetic response via multipolar Mie resonances and provides novel
opportunities for nanoscale nonlinear optics. Here, we observe strong second
harmonic generation from AlGaAs nanoantennas driven by both electric and magnetic
resonances. We distinguish experimentally the contribution of electric and
magnetic nonlinear response by analyzing the structure of polarization states of
vector beams in the second-harmonic radiation. We control continuously the
transition between electric and magnetic nonlinearities by tuning polarization of
the optical pump. Our results provide a direct observation of nonlinear optical
magnetism through selective excitation of multipolar nonlinear modes in
nanoantennas.
PMID- 28511013
TI - Reversible, Tunable, Electric-Field Driven Assembly of Silver Nanocrystal
Superlattices.
AB - Nanocrystal superlattices are typically fabricated by either solvent evaporation
or destabilization methods that require long time periods to generate highly
ordered structures. In this paper, we report for the first time the use of
electric fields to reversibly drive nanocrystal assembly into superlattices
without changing solvent volume or composition, and show that this method only
takes 20 min to produce polyhedral colloidal crystals, which would otherwise need
days or weeks. This method offers a way to control the lattice constants and
degree of preferential orientation for superlattices and can suppress the
uniaxial superlattice contraction associated with solvent evaporation. In situ
small-angle X-ray scattering experiments indicated that nanocrystal superlattices
were formed while solvated, not during drying.
PMID- 28511015
TI - Multistereocenter-Containing Cyclopentanoids from Ynamides via Oxazolidinone
Controlled Nazarov Cyclization.
AB - Achieving ready-enantioselective access to multistereocenter-containing
cyclopentyl rings is an area of great significance to organic synthesis. In this
work, we describe a general protocol for accessing multistereocenter-containing
cyclopentanoids from simple N-alkynyloxazolidinones (Ox-ynamides). This protocol
involves conversion of Ox-ynamides into Ox-activated divinyl and aryl vinyl
ketones that undergo facile Nazarov cyclization with excellent chemo-, regio-,
and stereocontrol. The Ox auxiliary directs all aspects of reactivity and
selectivity, both in the electrocyclization and in the subsequent transformations
of the resulting oxyallyl intermediate. Stereoinduction in the electrocyclization
results from a "coupled-torque" mechanism in which rotation of the Ox group,
driven by increasing orbital overlap of the nitrogen lone pair with the incipient
oxyallyl cation, is coupled with the rotation of the termini of the pentadienyl
cation, favoring a particular direction of conrotatory ring closure
(torquoselectivity). The associated lone-pair stabilization of the transition
state by Ox promotes cyclization of traditionally resistant substrates,
broadening the scope of this asymmetric Nazarov cyclization. The Ox group also
facilitates the stereo- and regioselective incorporation of nucleophiles (Nu) and
dienes, giving more complex, multistereocenter containing cyclopentanoids.
Finally, the Ox group is readily removed and recovered or can be converted into
other amine functionalities.
PMID- 28511014
TI - Protein Corona Formation on Colloidal Polymeric Nanoparticles and Polymeric
Nanogels: Impact on Cellular Uptake, Toxicity, Immunogenicity, and Drug Release
Properties.
AB - The adsorption of biomolecules to the surface of nanoparticles (NPs) following
administration into biological environments is widely recognized. In particular,
the "protein corona" is well understood in terms of formation kinetics and impact
upon the biological interactions of NPs. Its presence is an essential
consideration in the design of therapeutic NPs. In the present study, the protein
coronas of six polymeric nanoparticles of prospective therapeutic use were
investigated. These included three colloidal NPs-soft core-multishell (CMS) NPs,
plus solid cationic Eudragit RS (EGRS), and anionic ethyl cellulose (EC)
nanoparticles-and three nanogels (NGs)-thermoresponsive dendritic-polyglycerol
(dPG) nanogels (NGs) and two amino-functionalized dPG-NGs. Following incubation
with human plasma, protein coronas were characterized and their biological
interactions compared with pristine NPs. All NPs demonstrated protein adsorption
and increased hydrodynamic diameters, although the solid EGRS and EC NPs bound
notably more protein than the other tested particles. Shifts toward moderately
negative surface charges were also observed for all corona bearing NPs, despite
varied zeta potentials in their pristine states. While the uptake and cellular
adhesion of the colloidal NPs in primary human keratinocytes and human umbilical
vein endothelial cells were significantly decreased when bearing the protein
corona, no obvious impact was seen in the NGs. By contrast, corona bearing NGs
induced marked increases in cytokine release from primary human macrophages not
seen with corona bearing colloidal NPs. Despite this, no apparent enhancement to
in vitro toxicity was noted. Finally, drug release from EGRS and EC NPs was
assessed, where a decrease was seen in the EGRS NPs alone. Together these results
provide a direct comparison of the physical and biological impact the protein
corona has on NPs of widely varied character and in particular highlights a
distinction between the corona's effects on NGs and colloidal NPs.
PMID- 28511017
TI - Thermal Evolution of One-Dimensional Iodine Chains.
AB - In one-dimensional (1D) systems, the definition of three common states of matter
(solid, liquid, and gas) becomes obscure because it has been theoretically
predicted that a 1D system has no phase transition. Due to technical difficulty
in tracking 1D thermal evolution, hardly any experimental evidence has
demonstrated whether there exist these three states. Here we report Raman
experimental observation that 1D iodine molecular chains formed inside the
nanosized channel undergo continuous transformation from chain structure to
single molecules with increasing temperature, without having a sudden change as
commonly observed in phase transition. At low temperatures, short-range order
exists and manifests itself as long chains in structure, which gradually break
into shorter chains with increasing temperature. The 1D system progressively gets
more and more disordered, which is in agreement with the theoretical derivations.
Our work may benefit the emerging molecular scale electronics.
PMID- 28511016
TI - Structural and Biochemical Insights into Dimethylsulfoniopropionate Cleavage by
Cofactor-Bound DddK from the Prolific Marine Bacterium Pelagibacter.
AB - Enormous amounts of the organic osmolyte dimethylsulfoniopropionate (DMSP) are
produced in marine environments where bacterial DMSP lyases cleave it, yielding
acrylate and the climate-active gas dimethyl sulfide (DMS). SAR11 bacteria are
the most abundant clade of heterotrophic bacteria in the oceans and play a key
role in DMSP catabolism. An important environmental factor affecting DMS
generation via DMSP lyases is the availability of metal ions because they are
essential cofactors for many of these enzymes. Here we examine the structure and
activity of DddK in the presence of various metal ions. We have established that
DddK containing a double-stranded beta-helical motif utilizes various divalent
metal ions as cofactors for catalytic activity. However, nickel, an abundant
metal ion in marine environments, adopts a distorted octahedral coordination
environment and conferred the highest DMSP lyase activity. Crystal structures of
cofactor-bound DddK reveal key metal ion binding and catalytic residues and
provide the first rationalization for varying activities with different metal
ions. The structures of DddK along with site-directed mutagenesis and ultraviolet
visible studies are consistent with Tyr 64 acting as a base to initiate the beta
elimination reaction of DMSP. Our biochemical and structural studies provide a
detailed understanding of DMS generation by one of the ocean's most prolific
bacteria.
PMID- 28511018
TI - Daytime increase in caloric intake without change in total 24-h caloric intake
can increase adiposity but not total bodyweight in rats with inverted feeding
pattern.
AB - The goal of this study was to evaluate the effect of the food availability period
on body weight, self-selection of macronutrients, adiposity, lipoprotein, and
serum glucose profiles without changing energy intake. Young male rats were
divided into 2 groups according to the availability of food during the light and
dark phases of the cycle, forming 2 groups: control group (CG) and group with
inverted feeding pattern (IFPG). Before inversion of food availability on the
80th day, circadian food intake was measured every 4 h over 24 h during 3 days.
The glycemic curve, an oral test for glucose tolerance, and self-selection of
macronutrients were evaluated. Blood samples were collected for analysis of
fasting glucose, triglycerides, and total cholesterol fractions. The IFPG showed
an increase in fasting glucose in the dark phase of the cycle, changes in the
glycemic curve, and oral glucose tolerance test. It also showed increased
abdominal and liver fat and distinct choice of macronutrients compared with the
CG. A change in the availability of food according to the phase of the circadian
cycle produces changes in glucose and feeding circadian rhythm culminating in
increased abdominal and hepatic fat. These effects can increase the risk of
metabolic disorders and installation of chronic diseases.
PMID- 28511019
TI - A novel GRK1 mutation in an Italian patient with Oguchi disease.
PMID- 28511020
TI - Acute high-intensity interval running increases markers of gastrointestinal
damage and permeability but not gastrointestinal symptoms.
AB - The purpose of this study was to investigate the effects of high-intensity
interval running on markers of gastrointestinal (GI) damage and permeability
alongside subjective symptoms of GI discomfort. Eleven male runners completed an
acute bout of high-intensity interval training (HIIT) (eighteen 400-m runs at
120% maximal oxygen uptake) where markers of GI permeability, intestinal damage,
and GI discomfort symptoms were assessed and compared with resting conditions.
Compared with rest, HIIT significantly increased serum lactulose/rhamnose ratio
(0.051 +/- 0.016 vs. 0.031 +/- 0.021, p = 0.0047; 95% confidence interval (CI) =
0.006 to 0.036) and sucrose concentrations (0.388 +/- 0.217 vs. 0.137 +/- 0.148
mg.L-1; p < 0.001; 95% CI = 0.152 to 0.350). In contrast, urinary
lactulose/rhamnose (0.032 +/- 0.005 vs. 0.030 +/- 0.005; p = 0.3; 95% CI = -0.012
to 0.009) or sucrose concentrations (0.169% +/- 0.168% vs. 0.123% +/- 0.120%; p =
0.54; 95% CI = -0.199 to 0.108) did not differ between HIIT and resting
conditions. Plasma intestinal-fatty acid binding protein (I-FABP) was
significantly increased (p < 0.001) during and in the recovery period from HIIT
whereas no changes were observed during rest. Mild symptoms of GI discomfort were
reported immediately and at 24 h post-HIIT, although these symptoms did not
correlate to GI permeability or I-FABP. In conclusion, acute HIIT increased GI
permeability and intestinal I-FABP release, although these do not correlate with
symptoms of GI discomfort. Furthermore, by using serum sampling, we provide data
showing that it is possible to detect changes in intestinal permeability that is
not observed using urinary sampling over a shorter time-period.
PMID- 28511021
TI - The Selectivity Challenge in Organic Solvent Nanofiltration: Membrane and Process
Solutions.
AB - Recent development of organic solvent nanofiltration (OSN) materials has been
overwhelmingly directed toward tight membranes with ultrahigh permeance. However,
emerging research into OSN applications is suggesting that improved separation
selectivity is at least as important as further increases in membrane permeance.
Membrane solutions are being proposed to improve selectivity, mostly by
exploiting solute/solvent/membrane interactions and by fabricating tailored
membranes. Because achieving a perfect separation with a single membrane stage is
difficult, process engineering solutions, such as membrane cascades, are also
being advocated. Here we review these approaches to the selectivity challenge,
and to clarify our analysis, we propose a selectivity figure of merit that is
based on the permselectivity between the two solutes undergoing separation as
well as the ratio of their molecular weights.
PMID- 28511022
TI - Neurologie an der Universitat Leipzig. Beitrage zur Entwicklung des klinischen
Fachgebietes von 1880 bis 1985, by Armin Wagner and Holger Steinberg.
PMID- 28511023
TI - Efficacy of docosahexaenoic acid-choline-vitamin E in paediatric NASH: a
randomized controlled clinical trial.
AB - Nonalcoholic steatohepatitis (NASH), a progressive form of nonalcoholic fatty
liver disease, is one of the most common hepatic diseases in children. We
conducted a randomized controlled clinical trial on children with biopsy-proven
NASH based on a combinatorial nutritional approach compared with placebo.
Participants were assigned to lifestyle modification plus placebo or lifestyle
modification plus a mix containing docosahexaenoic acid, choline, and vitamin E
(DHA-CHO-VE). Forty children and adolescents participated in the entire trial.
The primary outcome was the improvement of liver hyperechogenicity. Secondary
outcomes included alterations of alanine aminotransferase (ALT) and other
metabolic parameters. Furthermore, changes of serum bile acids (BA) and plasma
fibroblast growth factor 19 (FGF19) levels were evaluated as inverse biomarkers
of disease severity. At the end of the study, we observed a significant decrease
in severe steatosis in the treatment group (50% to 5%, p = 0.001). Furthermore,
although the anthropometric and biochemical measurements in the placebo and DHA
CHO-VE groups were comparable at baseline, at the end of the study ALT and
fasting glucose levels improved only in the treatment group. Finally, we found
that BA levels were not influenced whereas FGF19 levels were significantly
increased by DHA-CHO-VE. The results suggest that a combination of DHA, VE, and
CHO could improve steatosis and reduce ALT and glucose levels in children with
NASH. However, further studies are needed to assess the impact of a DHA and VE
combination on repair of liver damage in paediatric NASH.
PMID- 28511024
TI - Cardiopulmonary Exercise Testing and Surgery.
AB - The surgical patient population is increasingly elderly and comorbid and poses
challenges to perioperative physicians. Accurate preoperative risk stratification
is important to direct perioperative care. Reduced aerobic fitness is associated
with increased postoperative morbidity and mortality. Cardiopulmonary exercise
testing is an integrated and dynamic test that gives an objective measure of
aerobic fitness or functional capacity and identifies the cause of exercise
intolerance. Cardiopulmonary exercise testing provides an individualized estimate
of patient risk that can be used to predict postoperative morbidity and
mortality. This technology can therefore be used to inform collaborative decision
making and patient consent, to triage the patient to an appropriate perioperative
care environment, to diagnose unexpected comorbidity, to optimize medical
comorbidities preoperatively, and to direct individualized preoperative exercise
programs. Functional capacity, evaluated as the anaerobic threshold and peak
oxygen uptake ([Formula: see text]o2peak) predicts postoperative morbidity and
mortality in the majority of surgical cohort studies. The ventilatory equivalents
for carbon dioxide (an index of gas exchange efficiency), is predictive of
surgical outcome in some cohorts. Prospective cohort studies are needed to
improve the precision of risk estimates for different patient groups and to
clarify the best combination of variables to predict outcome. Early data suggest
that preoperative exercise training improves fitness, reduces the debilitating
effects of neoadjuvant chemotherapy, and may improve clinical outcomes. Further
research is required to identify the most effective type of training and the
minimum duration required for a positive effect.
PMID- 28511028
TI - Corrigendum.
PMID- 28511026
TI - HDAC2 is required by the physiological concentration of glucocorticoid to inhibit
inflammation in cardiac fibroblasts.
AB - We previously suggested that endogenous glucocorticoids (GCs) may inhibit
myocardial inflammation induced by lipopolysaccharide (LPS) in vivo. However, the
possible cellular and molecular mechanisms were poorly understood. In this study,
we investigated the role of physiological concentration of GCs in inflammation
induced by LPS in cardiac fibroblasts and explored the possible mechanisms. The
results showed that hydrocortisone at the dose of 127 ng/mL (equivalent to
endogenous basal level of GCs) inhibited LPS (100 ng/mL)-induced productions of
TNF-alpha and IL-1beta in cardiac fibroblasts. Xanthine oxidase/xanthine (XO/X)
system impaired the anti-inflammatory action of GCs through downregulating HDAC2
activity and expression. Knockdown of HDAC2 restrained the anti-inflammatory
effects of physiological level of hydrocortisone, and blunted the ability of XO/X
system to downregulate the inhibitory action of physiological level of
hydrocortisone on cytokines. These results suggested that HDAC2 was required by
the physiological concentration of GC to inhibit inflammatory response. The
dysfunction of HDAC2 induced by oxidative stress might be account for GC
resistance and chronic inflammatory disorders during the cardiac diseases.
PMID- 28511025
TI - Co-inheritance of the membrane frizzled-related protein ocular phenotype and
glycogen storage disease type Ib.
AB - AIM: To report co-occurrence of two rare recessive conditions, the membrane
frizzled-related protein (MFRP)-related ocular phenotype and glycogen storage
disease type 1b (GSD-1b), in three siblings in an Omani family. BACKGROUND:
Biallelic mutations in the MFRP gene (chromosome 11q23) result in a distinct
ocular phenotype characterized by retinitis pigmentosa, foveoschisis, optic nerve
head drusen, and posterior microphthalmos. GSD-1b is an autosomal-recessive
disorder caused by mutations in SLC37A4 gene located in the same chromosomal
region. METHODS: An Omani family with three siblings diagnosed with GSD-1b
presented with ocular manifestations of progressive visual impairment and
diminution of night vision. All siblings underwent a standard ophthalmic and
clinical genetic evaluation. Full sequencing of the MFRP and SLC37A4 genes and
haplotype analysis was carried out. RESULTS: The three children (2F:1M) aged 13,
17, and 18 years were born to consanguineous parents. Their best-corrected visual
acuity ranged from 20/60 to 20/15. Ophthalmic exam revealed bilateral optic disc
drusen, foveoschisis, and pigmentary retinopathy, hyperopia of +12 to +15.5
diopters, and decreased axial length (15.8-16.39 mm) in all affected siblings.
Full-field electroretinography showed rod-cone dysfunction. Sequence analysis
revealed two novel variants in a homozygous state in the SLC37A4 and MFRP genes
in all the affected patients. CONCLUSIONS: We report the MFRP-related ocular
phenotype in three siblings with GSD-1b. Molecular genetic studies identified
novel mutations in the MFRP and SLC37A4 genes. Co-inheritance of a haplotype
harboring mutations in both loci on chromosome 11q23 resulted in co-occurrence of
the MFRP-related ocular phenotype and GSD-1b. This has not been reported
previously.
PMID- 28511027
TI - Ross-Konno Procedure With Cylinder Mitral Valve Replacement in 49 Days Old
Infant.
AB - A neonate with antenatally diagnosed severe aortic valve stenosis, left
ventricular outflow tract obstruction, left ventricular endocardial
fibroelastosis, and severe mixed mitral valve disease was admitted to our center
for balloon aortic valvuloplasty. On day 49, we performed a Ross-Konno procedure
and mitral valve replacement on the baby, whose weight was 3.4 kg. Right
ventricle-to-pulmonary artery continuity was restored with a handmade trileaflet
Gore-Tex conduit. We used a handmade cylindrical prosthesis made from
decellularized equine pericardium in the mitral position. We observed improvement
in left ventricular function and good performance of aortic, pulmonary, and
mitral prostheses at four months of follow-up.
PMID- 28511029
TI - Conceptualizing ethnicity in alcohol and drug research: Epidemiology meets social
theory.
AB - Since the 1990s, social scientists have rejected notions of ethnicity as
something static and discrete, instead highlighting the context-dependent and
fluid nature of multiple identities. In spite of these developments, researchers
within the substance use fields continue to assess ethnic group categories in
ways that suggest little critical reflection in terms of the validity of the
measurements themselves, nor the social, bureaucratic, and political decisions
shaping standard measures of ethnicity. This paper highlights these
considerations, while also acknowledging the role of socially-delineated ethnic
categorizations in documenting health inequities and social injustices. We call
on researchers in alcohol and drugs research to critically appraise their use of
ethnic categorizations, querying how to best measure ethnicity within their own
studies in ways that are justified beyond simplified explanations of social
convention and that "do no harm" in terms of perpetuating racism and obscuring
the roots causes of social and health problems related to alcohol and drugs.
PMID- 28511031
TI - Modeling the mental health service utilization decisions of university
undergraduates: A discrete choice conjoint experiment.
AB - OBJECTIVE: We modeled design factors influencing the intent to use a university
mental health service. PARTICIPANTS: Between November 2012 and October 2014, 909
undergraduates participated. METHOD: Using a discrete choice experiment,
participants chose between hypothetical campus mental health services. RESULTS:
Latent class analysis identified three segments. A Psychological/Psychiatric
Service segment (45.5%) was most likely to contact campus health services
delivered by psychologists or psychiatrists. An Alternative Service segment
(39.3%) preferred to talk to peer-counselors who had experienced mental health
problems. A Hesitant segment (15.2%) reported greater distress but seemed less
intent on seeking help. They preferred services delivered by psychologists or
psychiatrists. Simulations predicted that, rather than waiting for standard
counseling, the Alternative Service segment would prefer immediate access to E
Mental health. The Usual Care and Hesitant segments would wait 6 months for
standard counseling. CONCLUSIONS: E-Mental Health options could engage students
who may not wait for standard services.
PMID- 28511030
TI - Emotional approach coping and depressive symptoms in colorectal cancer patients:
The role of the intimate relationship.
AB - This study examined whether emotional approach coping was associated with lower
depressive symptoms, and whether intimacy moderated this association, in 121
married/partnered colorectal cancer (CRC) outpatients. Prospective analyses of
survey data on emotional approach coping, depressive symptoms, and intimacy
measured at baseline and 6-month follow-up showed that depressive symptoms were
inversely related to processing, expression, and intimacy. At baseline, the
association between processing and depressive symptoms was moderated by intimacy:
greater processing was associated with lower depressive symptoms only for those
in relatively high-intimacy relationships. Enhancing emotional approach coping
efforts and relationship quality may benefit CRC patients' adjustment.
PMID- 28511032
TI - Correlates of health-related quality of life in patients with myocardial
infarction: A literature review.
AB - BACKGROUND: By the increasing emphasis on health-related quality of life (HRQoL)
in patients with myocardial infarction (MI), it is necessary to explore factors
that affect HRQoL in this population. OBJECTIVES: This study aimed to identify
correlates of HRQoL in patients with MI. DESIGN: A literature review of the
factors that affect HRQoL in patients with MI (1995-2016). DATA SOURCES: Three
main databases-CINAHL, MEDLINE and PsychINFO-were searched to retrieve relevant
peer-reviewed articles published in English. REVIEW METHODS: In consultation with
a medical librarian, we identified relevant MeSH terms and used them for
searching the literature: health-related quality of life/quality of
life/HRQoL/QoL, myocardial infarction/heart attack/MI and predict*/factor. Data
elements were extracted and narratively described variables synthesised into four
categories. RESULTS: A total of 48 studies met the inclusion criteria and were
included in the review. Correlates of HRQoL in patients with MI were identified
in the following categories: demographic, behavioural, disease-related, and
psychosocial factors. Specific correlates included age and gender-identity for
demographic factors; physical activity and smoking for behavioural factors;
severity of MI, symptoms, and comorbidities for disease-related factors; anxiety
and depression for psychosocial factors. CONCLUSIONS: Identifying correlates of
HRQoL can help identify patients who are at risk for poor HRQoL in the recovery
or rehabilitation stage of post-MI. Future intervention should focus on
adjustable correlates such as behavioural and psychosocial factors to promote
HRQoL among patients after experiencing MI.
PMID- 28511033
TI - Comparing adult cannabis treatment-seekers enrolled in a clinical trial with
national samples of cannabis users in the United States.
AB - BACKGROUND: Cannabis use rates are increasing among adults in the United States
(US) while the perception of harm is declining. This may result in an increased
prevalence of cannabis use disorder and the need for more clinical trials to
evaluate efficacious treatment strategies. Clinical trials are the gold standard
for evaluating treatment, yet study samples are rarely representative of the
target population. This finding has not yet been established for cannabis
treatment trials. This study compared demographic and cannabis use
characteristics of a cannabis cessation clinical trial sample (run through
National Drug Abuse Treatment Clinical Trials Network) with three nationally
representative datasets from the US; 1) National Survey on Drug Use and Health,
2) National Epidemiologic Survey on Alcohol and Related Conditions-III, and 3)
Treatment: Episodes Data Set - Admissions. METHODS: Comparisons were made between
the clinical trial sample and appropriate cannabis using sub-samples from the
national datasets, and propensity scores were calculated to determine the degree
of similarity between samples. RESULTS: showed that the clinical trial sample was
significantly different from all three national datasets, with the clinical trial
sample having greater representation among older adults, African Americans,
Hispanic/Latinos, adults with more education, non-tobacco users, and daily and
almost daily cannabis users. CONCLUSIONS: These results are consistent with
previous studies of other substance use disorder populations and extend sample
representation issues to a cannabis use disorder population. This illustrates the
need to ensure representative samples within cannabis treatment clinical trials
to improve the generalizability of promising findings.
PMID- 28511035
TI - On the context dependency of implicit self-esteem in social anxiety disorder.
AB - BACKGROUND AND OBJECTIVES: Cognitive models assume that negative self-evaluations
are automatically activated in individuals with Social Anxiety Disorder (SAD)
during social situations, increasing their individual level of anxiety. This
study examined automatic self-evaluations (i.e., implicit self-esteem) and state
anxiety in a group of individuals with SAD (n = 45) and a non-clinical comparison
group (NC; n = 46). METHODS: Participants were randomly assigned to either a
speech condition with social threat induction (giving an impromptu speech) or to
a no-speech condition without social threat induction. We measured implicit self
esteem with an Implicit Association Test (IAT). RESULTS: Implicit self-esteem
differed significantly between SAD and NC groups under the speech condition but
not under the no-speech condition. The SAD group showed lower implicit self
esteem than the NC group under the speech-condition. State anxiety was
significantly higher under the speech condition than under the no-speech
condition in the SAD group but not in the NC group. Mediation analyses supported
the idea that for the SAD group, the effect of experimental condition on state
anxiety was mediated by implicit self-esteem. LIMITATIONS: The causal relation
between implicit self-esteem and state anxiety could not be determined.
CONCLUSION: The findings corroborate hypotheses derived from cognitive models of
SAD: Automatic self-evaluations were negatively biased in individuals with SAD
facing social threat and showed an inverse relationship to levels of state
anxiety. However, automatic self-evaluations in individuals with SAD can be
unbiased (similar to NC) in situations without social threat.
PMID- 28511034
TI - School collective occupation movements and substance use among adolescents: A
school-level panel design.
AB - BACKGROUND: Recently, social movements across the world have demanded reforms to
education systems and other institutions. Although such movements have affected
large numbers of people across multiple countries, we know little about the
impacts they have had on population health. We focus on one example: the massive
strikes and collective occupation of secondary schools across Chile, which
occurred contemporaneously with a large increase in marijuana use among students
in this age group. We aimed to evaluate the causal effects that the 2011 Chilean
school strikes had on adolescent substance use, including the initiation of
marijuana use and the use of alcohol and marijuana. METHODS: School-level,
aggregated panel design using data from the National Drug Surveys among Secondary
Students from 2005 to 2015 for students in grades 9-12. We used a fixed-effects
difference-in-difference model to estimate the effect of school occupations on
prevalence of self-reported indicators of drug use. RESULTS: Reported marijuana
use doubled between 2009 and 2013 among Chilean adolescents. After controlling
for secular trends in outcomes and for school characteristics, there was no
evidence of increased marijuana initiation, alcohol and marijuana use, or of an
increase in heavy use among adolescents being directly attributable to school
strikes and occupations in 2011. CONCLUSIONS: The 2011 Occupy school movement in
Chile had no detectable causal effect on substance use among Chilean adolescents.
The increase in marijuana use from 2009 to 2013 seems to be part of broader
social changes occurring among the school-age population.
PMID- 28511036
TI - Proliferation.
PMID- 28511037
TI - Role of pH and ionic strength in the aggregation of TiO2 nanoparticles in the
presence of extracellular polymeric substances from Bacillus subtilis.
AB - Increased use of commercial titanium dioxide nanoparticles (TiO2 NPs) in consumer
products most likely leads to their additional environmental release. Aggregation
and disaggregation processes are expected to play an important role in the fate
and transport of TiO2 NPs in natural aquatic ecosystems. Therefore, in this work,
we have studied the colloidal stability of TiO2 NPs in the presence of
extracellular polymeric substances (EPS) from Bacillus subtilis and the
adsorption behavior of EPS on TiO2 NPs in aqueous solutions at different pH
values and ionic strengths (IS). The adsorption and aggregation processes were
found to depend on the solution chemistry. The mass fraction of EPS on TiO2 NPs
decreased with increased pH and NaCl concentrations, which was verified by
Fourier transform infrared spectroscopy. The presence of EPS can substantially
influence the colloidal stability of TiO2 NPs. In deionized water, the
aggregation of NPs was induced by the addition of EPS only when the pH was below
the TiO2 NP point of zero charge (~6). When the pH was equal to pHPZC, TiO2, the
TiO2 NPs would rapidly form large aggregates, but the adsorption of EPS leads to
partial fragmentation via electrostatic repulsion and steric hindrance. When the
pH was greater than pHPZC, TiO2, the aggregation rate was minimally affected by
the increased EPS concentration. In NaCl solution, the aggregation rate of TiO2
NPs obviously increased with increased NaCl concentration. The critical
coagulation concentration (CCC) of TiO2 NPs is 13.9 mM in the absence of EPS and
increases to 155.6, 213.7 and 316.4 mM in the presence of 1, 5 and 10 mg/L EPS in
NaCl solution, respectively, which indicates that the steric hindrance occurs
after the addition of EPS. This study suggests that environmental conditions and
EPS concentration greatly modify the colloidal stability of TiO2 nanoparticles.
PMID- 28511038
TI - Attributable risks of emergency hospital visits due to air pollutants in China: A
multi-city study.
AB - Air pollution is associated with risks of mortality in China, but the evidence is
still limited for morbidity. This study aims to examine overall effects of
ambient air pollutants on emergency hospital visits (EHVs) at the national level
in China and calculate corresponding attributable risks. We collected daily data
for EHVs from 33 largest hospitals in China between Oct 2013 and Dec 2014, as
well as daily measurements of particulate matter (PM10 and PM2.5: particles with
aerodynamic diameter < 10 MUm and 2.5 MUm, respectively), nitrogen dioxide (NO2)
and sulphur dioxide (SO2) from 31 cities where the hospitals were located.
Firstly, quasi-Poisson regression with a constrained distributed lag model (CDLM)
was employed to examine city-specific associations of EHVs with each pollutant.
Then, the effects at the national scale were pooled with a random-effect meta
analysis. Daily EHVs was significantly associated with a 10 MUg/m3 increase in
PM2.5 at lag 0-2 days [cumulative relative risk (RR) and 95% confidence intervals
(CI): 1.006 (1.002, 1.009)], PM10 at lag 0-1 days [1.004 (1.002, 1.006)], NO2 at
lag 0-1 days [1.015 (1.010, 1.019)] and SO2 at lag 0-2 days [1.022 (1.014,
1.030)]. The effect estimates were not modified by sex, but stronger effects were
observed among children than adults. Overall, 3.34% of EHVs may result from
exposure to ambient PM2.5, 3.96% to PM10, 5.90% to NO2 and 5.38% to SO2. Exposure
to outdoor air pollution has acute effects on EHVs. Effective measures to control
air pollution levels in China could potentially reduce demands for emergency
hospital services.
PMID- 28511039
TI - Occurrence, composition, source, and regional distribution of halogenated flame
retardants and polybrominated dibenzo-p-dioxin/dibenzofuran in the soils of
Guiyu, China.
AB - Guiyu, China, is well-known for the crude disposal of electronic waste (EW) and
severe persistent organic pollutants (POPs). Therefore, in this study, the
occurrence, composition, and source of polybrominated diphenyl ethers (PBDEs),
2,2',4,4',5,5'-hexabromobiphenyl (BB153), some novel brominated flame retardants
(NBFRs), Dechlorane Plus (DP) and polybrominated dibenzo-p-dioxins/dibenzofurans
(PBDD/Fs) in farmland soils covering Guiyu were studied. In EW disposal area
soils, PBDEs were the most abundant FRs, with concentrations of 13-1014 ng g-1.
The primary PBDE sources were technical Penta- and Deca-BDE mixtures in northern
and southern Guiyu, respectively. The levels of BB153 were relatively low,
possibly because it has been banned in the 1970s. The concentrations of
hexabromobenzene (HBB) were 0.048-3.3 ng g-1, while pentabromoethylbenzene (PBEB)
was almost not detected in the soils. Two alternatives to commercial PBDEs,
decabromodiphenyl ethane (DBDPE) and 1,2-bis(2,4,6-tribromophenoxy) ethane
(BTBPE), were the primary NBFRs, with concentrations of 1.8-153 ng g-1 and 0.43
15 ng g-1, respectively. DP was another primary FR, with concentrations of 0.57
146 ng g-1. Moreover, syn-DP and anti-DP isomers were not stereoselectively
decomposed during the EW disposal process and were therefore present in their
original fractions in the soils. The levels of PBDD/Fs in EW disposal area soils
were 2.5-17 pg TEQ g-1. 1,2,3,4,6,7,8-HpBDF and OBDF were the dominant congeners,
mainly derived from processing, pyrolysis and combustion of BFRs. The regional
distribution of pollutants was shown to be related to the disposal manner of EW,
with their open thermal disposal tending to release more highly brominated
compounds such as BDE209, DBDPE, and 1,2,3,4,6,7,8-HpBDF. Additionally, some
riverbank sites were heavily polluted because of nearby point sources, downwind
Simapu (SMP) town without EW disposal activity was also contaminated by these
pollutants.
PMID- 28511040
TI - Removal of selected PPCPs, EDCs, and antibiotic resistance genes in landfill
leachate by a full-scale constructed wetlands system.
AB - Landfill leachate could be a significant source of emerging contaminants (ECs)
and antibiotic resistance genes (ARGs) into the environment. This study provides
the first information on the occurrence of selected ECs and ARGs in raw leachate
from 16-year old closed landfill site in Singapore. Among the investigated ECs,
acetaminophen (ACT), bisphenol A (BPA), clofibric acid (CA), caffeine (CF),
crotamiton (CTMT), diclofenac (DCF), N,N-diethyl-m-toluamide (DEET), gemfibrozil
(GFZ), lincomycin (LIN), salicylic acid (SA), and sulfamethazine (SMZ) were the
most frequently detected compounds in raw landfill leachate. The concentrations
of detected ECs in raw landfill leachate varied significantly, from below
quantification limit to 473,977 ng/L, depending on the compound. In this study,
Class I integron (intl1) gene and ten ARGs were detected in raw landfill
leachate. Sulfonamide resistance (sul1, sul2, and dfrA), aminoglycoside
resistance (aac6), tetracycline resistance (tetO), quinolone resistance (qnrA),
and intl1 were ubiquitously present in raw landfill leachate. Other resistance
genes, such as beta-lactam resistance (blaNMD1, blaKPC, and blaCTX) and macrolide
lincosamide resistance (ermB) were also detected, detection frequency of <50%.
The removal of target ECs and ARGs by a full-scale hybrid constructed wetland
(CW) was also evaluated. The vast majority of ECs exhibited excellent removal
efficiencies (>90%) in the investigated hybrid CW system. This hybrid CW system
was also found to be effective in the reduction of several ARGs (intl1, sul1,
sul2, and qnrA). Aeration lagoons and reed beds appeared to be the most important
treatment units of the hybrid CW for removing the majority of ECs from the
leachate.
PMID- 28511041
TI - Biofilm formation and granule properties in anaerobic digestion at high salinity.
AB - For the anaerobic biological treatment of saline wastewater, Anaerobic Digestion
(AD) is currently a possibility, even though elevated salt concentrations can be
a major obstacle. Anaerobic consortia and especially methanogenic archaea are
very sensitive to fluctuations in salinity. When working with Upflow Sludge
Blanket Reactor (UASB) technology, in which the microorganisms are aggregated and
retained in the system as a granular biofilm, high sodium concentration
negatively affects aggregation and consequently process performances. In this
research, we analysed the structure of the biofilm and granules formed during the
anaerobic treatment of high salinity (at 10 and 20 g/L of sodium) synthetic
wastewater at lab scale. The acclimated inoculum was able to accomplish high
rates of organics removal at all the salinity levels tested. 16S rRNA gene clonal
analysis and Fluorescence In Situ Hybridization (FISH) analyses identified the
acetoclastic Methanosaeta harundinacea as the key player involved acetate
degradation and microbial attachment/granulation. When additional calcium (1 g/L)
was added to overcome the negative effect of sodium on microbial aggregation,
during the biofilm formation process microbial attachment and acetate degradation
decreased. The same result was observed on granules formation: while calcium had
a positive effect on granules strength when added to UASB reactors, Methanosaeta
filaments were not present and the degradation of the partially acidified
substrate was negatively influenced. This research demonstrated the possibility
to get granulation at high salinity, bringing to the forefront the importance of
a selection towards Methanosaeta cells growing in filamentous form to obtain
strong and healthy granules.
PMID- 28511042
TI - Controllable synthesis of hierarchical MnOx/TiO2 composite nanofibers for
complete oxidation of low-concentration acetone.
AB - A novel hierarchical MnOx/TiO2 composite nanofiber was fabricated by combining
the electrospinning technique and hydrothermal growth method. The synthesized
nanomaterial, which comprised primary TiO2 nanofibers and secondary MnOx
nanoneedles, was further investigated for complete catalytic oxidation of
volatile organic compounds for the first time, and this presented high-oxidation
performance on low-concentration acetone. The morphological, structural,
physicochemical characterization, and catalytic performance analyses demonstrated
that the highest catalytic activity was achieved from the obtained MnOx/TiO2
nanofiber catalyst with 30wt.% manganese loading. This finding can be ascribed to
the synergistic effect of the specific hierarchical nanofibrous morphology, the
abundant surface-adsorbed oxygen, the superior redox property, and the sufficient
specific surface.
PMID- 28511044
TI - Bentonite modified with zinc enhances aflatoxin B1 adsorption and increase
survival of fibroblasts (3T3) and epithelial colorectal adenocarcinoma cells
(Caco-2).
AB - Bentonites are commonly used as feed additives to reduce the bioavailability and
thus the toxicity of aflatoxins by adsorbing the toxins in the gastrointestinal
tract. Aflatoxins are particular harmful mycotoxins mainly found in areas with
hot and humid climates. They occur in food and feedstuff as a result of fungal
contamination before and after harvest. The aim of this study was to modify
Brazilian bentonite clay by incorporation of zinc (Zn) ions in order to increase
the adsorption capacity and consequently reduce the toxicity of aflatoxins. The
significance of Zn intercalating conditions such as concentration, temperature
and reaction time were investigated. Our results showed that the Zn treatment of
the bentonite increased the aflatoxin B1 (AFB1) adsorption and that Zn
concentration had a negative effect. Indeed, temperature and time had no
significant effect in the binding capacity. The modified bentonite (Zn-Bent1) was
not cytotoxic to either fibroblasts (3T3) nor epithelial colorectal
adenocarcinoma cells (Caco-2) cell lines. Interestingly, Zn-Bent1 has higher
protective effect against AFB1 induced cytotoxicity than the unmodified
bentonite. In conclusion, the Zn modified bentonite, Zn-Bent1, represent an
improved tool to prevent aflatoxicosis in animals fed on AFB1 contaminated feed.
PMID- 28511043
TI - Environmental behavior of 12 UV filters and photocatalytic profile of ethyl-4
aminobenzoate.
AB - Ethyl-4-aminobenzoate (Et-PABA) is currently used as a substitute for 4
aminobenzoate (PABA) in sunscreens and anesthetic ointments. Despite its
widespread use and hydrophilicity, Et-PABA has never been found in environmental
waters. This study, probed the occurrence of Et-PABA in both seawater and
drinking water sources in Hong Kong, and evaluated its transformation products
(TPs) and environmental fate via cumulative potency and photocatalytic profile
analyses. Another 11 UV filters used in skin-care products were also studied. Et
PABA was not detected in any water sample. Four other UV filters were dominant at
ng/L level in both seawater and drinking water sources. UHPLC-QTOF-MS was used to
elucidate the structure of TPs. With high resolution accurate mass data and
fragment rationalization, 11 Et-PABA TPs were characterized, including seven
intermediates firstly proposed as TPs; two compounds were reported for the first
time. It is proposed that photocatalysis induces transformation pathways of
(de)hydroxylation, demethylation and molecular rearrangement. Luminescent
bacteria tests showed decreasing toxicity with increasing irradiation of Et-PABA,
suggesting that irradiation TPs are less toxic than the parent compound.
Transformation of Et-PABA appears to explain why Et-PABA has not been detected in
the natural environment.
PMID- 28511045
TI - Stigma and diurnal cortisol among transitioning transgender men.
AB - This study assessed diurnal cortisol functioning in relation to stigma-based
transition-specific stressors experienced by transgender men during their
transition from female to male. Sixty-five healthy transgender men undergoing
testosterone therapy participated in in-person interviews through which
transition-specific stressors were identified. Interviews were coded according to
participant reported (1) Transitioning-identity stress; (2) Coming Out stress;
(3) Gender-specific Public Bathroom stress; and (4) levels of general Perceived
Stress. Participants provided fifteen salivary samples assessing cortisol diurnal
rhythm over three days. Hierarchical linear models, adjusted for duration of time
on testosterone therapy, body mass index, steroid-related medication use, mean
awakening time, and CAR, confirmed that elevated diurnal cortisol levels at
awakening were associated with transition-specific social stressors including
experiencing Transitioning-identity stress, frequent Coming Out stress, and
Gender-specific Public Bathroom stress. Transitioning-identity stress and Gender
specific Public Bathroom stress also predicted a steeper negative slope at
awakening. General Perceived Stress was not associated with elevated cortisol or
slope. These results clarify the relation of increased cortisol at awakening with
a negative linear slope to perceived stigma and transition-related stress
experience among transgender men.
PMID- 28511046
TI - Effects of stress on women's preference for male facial masculinity and their
endocrine correlates.
AB - Women's preferences for masculinity in men's faces seem to vary across the
menstrual cycle and are assumed to be strongest around ovulation. A number of
hormones have been proposed to underlie these subtle cyclic shifts. Furthermore,
mating preferences are context-dependent, and stress has been found to alter mate
choice, both in animals and humans. Currently, the effects of stress on women's
preference for masculinity remain unknown. To examine the hormonal basis and the
impact of stress on facial masculinity preference, we tested for within-subject
changes in 52 healthy young women who underwent the Trier Social Stress Test
(TSST) and the placebo-TSST in randomized order in the late follicular and mid
luteal phases of their menstrual cycle. Menstrual cycle phase and hormone levels
were confirmed using estradiol, testosterone, progesterone, and cortisol analyses
from saliva. Results show that women were more likely to be attracted to
masculine-faced men right before ovulation than in the mid-luteal phase.
Estradiol modulated this masculinity preference with high estradiol levels being
related to stronger masculinity preference. When stressed however, women
experienced a decrease in male facial masculinity preference. In line with these
findings, the higher the cortisol increase to stress, the less were masculine
faces preferred to more feminine faces. Mate choice is a central component of
reproduction. The present results provide information about the effects of stress
and hormonal influences on mate preferences in women.
PMID- 28511047
TI - Birth weight and postnatal growth in preterm born children are associated with
cortisol in early infancy, but not at age 8 years.
AB - BACKGROUND: Preterm birth has been associated with altered hypothalamic-pituitary
adrenal (HPA-) axis activity as well as cardiometabolic diseases and
neurodevelopmental impairments later in life. We assessed cortisol from term age
to age 8 y in children born preterm, to explore the development of HPA-axis
activity in association with intrauterine and early-postnatal growth until 6 mo.
corrected age. METHODS: In 152 children born at a gestational age <=32 wks.
and/or with a birth weight <=1,500g, random serum cortisol was assessed at term
age (n=150), 3 mo. (n=145) and 6 mo. corrected age (n=144), and age 8 y (n=59).
Salivary cortisol was assessed at age 8 y (n=75): prior to bedtime, at awakening,
15min after awakening, and before lunch. Cortisol was analyzed in association
with birth weight-standard deviation score (SDS), being born small for
gestational age (SGA), and combinations of intrauterine and postnatal growth:
appropriate for gestational age (AGA) with or without growth restriction (AGA GR+
or AGA GR-) at 6 mo. corrected age, and SGA with or without catch-up growth (SGA
CUG+ or SGA CUG-) at 6 mo. corrected age. Cross-sectional associations at all
time points were analyzed using linear regression, and longitudinal associations
were analyzed using generalized estimating equations. RESULTS: Longitudinally,
birth weight-SDS was associated with cortisol (beta [95%CI]): lower cortisol over
time was seen in infants with a birth weight <=-2 SDS (-50.69 [-94.27; -7.11],
p=0.02), infants born SGA (-29.70 [-60.58; 1.19], p=0.06), AGA GR+ infants (
55.10 [-106.02; -4.17], p=0.03) and SGA CUG- infants (-61.91 [-104.73; -19.10],
p=0.01). In cross-sectional analyses at age 8 y, no associations were found
between either serum or salivary cortisol and birth weight-SDS, SGA-status, or
growth from birth to 6 mo. corrected age. CONCLUSION: In children born preterm,
poor intrauterine and postnatal growth were associated with lower cortisol in
early infancy, but not at age 8 y. Even though HPA-axis activity no longer
differed between groups at age 8 y, or differences could not be confirmed due to
attrition, it is unknown whether the differences found in early infancy could
attribute to increased health risks later in life.
PMID- 28511048
TI - Defensive freezing links Hypothalamic-Pituitary-Adrenal-axis activity and
internalizing symptoms in humans.
AB - The Hypothalamic-Pituitary-Adrenal (HPA)-axis plays an important role in the
expression of defensive freezing. Adaptive freezing reactivity, characterized by
an immediate increase in acute stress and timely termination upon threat offset
or need to act, is essential for adequate stress coping. Blunted HPA-axis
activity in animals is associated with blunted freezing reactivity and
internalizing symptoms. Despite their potential relevance, it remains unknown
whether these mechanisms apply to humans and human psychopathology. Using a well
established method combining electrocardiography and posturography, we assessed
freezing before, immediately after, and one hour after a stress induction in 92
human adolescents. In line with animal models, human adolescents showed stress
induced freezing, as quantified by relative reductions in heart rate and body
sway after, as compared to before, stress. Moreover, relatively lower basal
cortisol was associated with reduced stress-induced freezing reactivity (i.e.,
less immediate freezing and less recovery). Path analyses showed that decreased
freezing recovery in individuals with reduced cortisol levels was associated with
increased levels of internalizing symptoms. These findings suggest that reduced
freezing recovery may be a promising marker for the etiology of internalizing
symptoms.
PMID- 28511049
TI - The Omega-3 Index and relative risk for coronary heart disease mortality:
Estimation from 10 cohort studies.
AB - BACKGROUND AND AIMS: A recent 19-cohort meta-analysis examined the relationships
between biomarkers of omega-3 fatty acids and risk for coronary heart disease
(CHD). That study did not, however, report hazard ratios (HRs) specifically as a
function of erythrocyte eicosapentaenoic (EPA) plus docosahexaenoic (DHA) levels,
a metric called the Omega-3 Index in which EPA + DHA content is expressed as a
percent of total fatty acids. The Omega-3 Index has been used in several recent
studies and is a validated biomarker of omega-3 fatty acid tissue levels, but
additional data are needed to confirm (or refute) the originally-proposed
clinical cut-points of <4% (higher risk) and 8%-12% (lower risk). METHODS: The
present study was therefore undertaken using published data from this meta
analysis to estimate HRs per 1-SD increase in the Omega-3 Index and median
quintile values for this metric across 10 of the cohorts for which the needed
data were available. RESULTS: The overall mean (SD) for the Omega-3 Index in
these 10 cohort studies was 6.1% (2.1%), and the HR for a 1-SD increase was 0.85
(95% confidence interval, 0.80-0.91). Median quintile 1 and 5 levels were 4.2%
vs. 8.3%, respectively. Based on these values, we estimate that risk for fatal
CHD would have been reduced by about 30% moving from an Omega-3 Index of 4%-8%.
CONCLUSIONS: These findings support the use of <4% and >8% as reasonable
therapeutic targets for the Omega-3 Index.
PMID- 28511050
TI - Maternal distress in late pregnancy alters obstetric outcomes and the expression
of genes important for placental glucocorticoid signalling.
AB - The experience of maternal distress in pregnancy is often linked with poorer
obstetric outcomes for women as well as adverse outcomes for offspring.
Alterations in placental glucocorticoid signalling and subsequent increased fetal
exposure to cortisol have been suggested to underlie this relationship. In the
current study, 121 pregnant women completed the Perceived Stress Scale, State
Trait Anxiety Inventory and Edinburgh Postnatal Depression Scale in the third
trimester of pregnancy. Placental samples were collected after delivery. Maternal
history of psychiatric illness and miscarriage were significant predictors of
poorer mental health in pregnancy. Higher anxiety was associated with an increase
in women delivering via elective Caesarean Section, and an increase in bottle
feeding. Birth temperature was mildly reduced among infants of women with high
levels of depressive symptomology. Babies of mothers who scored high in all
stress (cumulative distress) measures had reduced 5-min Apgar scores. High
cumulative distress reduced the expression of placental HSD11B2 mRNA and
increased the expression of placental NR3C1 mRNA. These data support a role for
prenatal distress as a risk factor for altered obstetric outcomes. The
alterations in placental gene expression support a role for altered placental
glucocorticoid signalling in the relationship between maternal prenatal distress
and adverse outcomes.
PMID- 28511051
TI - A one-year longitudinal qualitative study of peer support services in a non
Western context: The perspectives of peer support workers, service users, and co
workers.
AB - This study explored the changing views of key stakeholders (peer support workers,
their co-workers, and service users) about peer support services in a non-Western
community, using a longitudinal qualitative approach. Five trainee peer support
workers (PSWs), 15 service users, and 14 co-workers were interviewed over a 12
month period, under the auspices of the Peer Support Workers Project (also known
as the Mindset project) in Hong Kong. A total of 77 interviews were transcribed
and thematic analyses were conducted across the participant groups at three
different time points (training, work placements, and employment). During the
initial implementation of the services, uncertainty about the role of the PSWs
were reported. However, trusting and beneficial relationships with service users
were gradually built, showing growing resilience and confidence over time. The
participants realized that PSWs' experiences of mental illnesses were a unique
asset that could help service users to alleviate their own somatic symptoms and
improve their connections with others. Our findings highlight that the
perceptions of peer support services changed from confusion to viewing PSWs as an
asset, to an awareness of the importance of family support, and to the belief
that implementing such a program will benefit both service users and PSWs.
PMID- 28511053
TI - Opioid analgesics and heroin: Examining drug misuse trends among a sample of drug
treatment clients in Kentucky.
AB - BACKGROUND: In an effort to mitigate Kentucky's prescription drug misuse,
legislative intervention efforts were introduced in 2012 and 2013 to better
regulate pain clinics, prescribed use of opioid analgesics, and to expand the
monitoring of opioid prescriptions. The focus of this paper is primarily on
opioid analgesics and heroin and the relationship of use/misuse patterns of these
drugs to state drug policy initiatives. METHODS: A secondary data analysis of
drug treatment clients (N=52,360) was conducted to project illicit drug use
trends in Kentucky. This study describes temporal and geographic trends of self
reported illicit drug use among individuals in state-funded treatment in Kentucky
between fiscal year 2010 and fiscal year 2013. RESULTS: Significant reductions in
the prevalence of illicit opioid use, declined from fiscal year 2010 to fiscal
year 2013 (p<.01, CI=-.298 to -.215). However, heroin use rates significantly
increased over the years studied, suggesting there may be a transition from
prescription opioids to heroin (p<.01, CI=.143 to .178). The analysis suggests
these trends may continue. CONCLUSIONS: Findings suggest Kentucky's legislative
efforts were effective in reducing illicit prescription opioid use, but heroin
use has increased. One possible explanation for this relationship is that as
prescription opioids became more difficult to obtain, users turned to heroin as a
substitute. The finding of rising heroin use suggests a need for further policy
initiatives to reduce heroin use, but the potential effectiveness of this policy
remains unclear. Understanding trends may help to guide future policy efforts and
pain management treatment strategies to where they might have their greatest
impact.
PMID- 28511052
TI - Phosphate regulates chondrogenesis in a biphasic and maturation-dependent manner.
AB - Inorganic phosphate (Pi) has been recognized as an important signaling molecule
that modulates chondrocyte maturation and cartilage mineralization. However,
conclusive experimental evidence for its involvement in early chondrogenesis is
still lacking. Here, using high-density monolayer (2D) and pellet (3D) culture
models of chondrogenic ATDC5 cells, we demonstrate that the cell response to Pi
does not correlate with the Pi concentration in the culture medium but is better
predicted by the availability of Pi on a per cell basis (Pi abundance). Both
culture models were treated with ITS+, 10mM beta-glycerophosphate (betaGP), or
ITS+/10mM betaGP, which resulted in three levels of Pi abundance in cultures:
basal (Pi/DNA <10ng/ug), moderate (Pi/DNA=25.3 - 32.3ng/ug), and high abundance
(Pi/DNA >60ng/ug). In chondrogenic medium alone, the abundance levels were at the
basal level in 2D culture and moderate in 3D cultures. The addition of 10mM
betaGP resulted in moderate abundance in 2D and high abundance in 3D cultures.
Moderate Pi abundance enhanced early chondrogenesis and production of aggrecan
and type II collagen whereas high Pi abundance inhibited chondrogenic
differentiation and induced rapid mineralization. Inhibition of sodium phosphate
transporters reduced phosphate-induced expression of chondrogenic markers. When
3D ITS+/betaGP cultures were treated with levamisole to reduce ALP activity, Pi
abundance was decreased to moderate levels, which resulted in significant
upregulation of chondrogenic markers, similar to the response in 2D cultures.
Delay of phosphate delivery until after early chondrogenesis occurs (7 days) no
longer enhanced chondrogenesis, but instead accelerated hypertrophy and
mineralization. Together, our data highlights the dependence of chondroprogenitor
cell response to Pi on its availability to individual cells and the chondrogenic
maturation stage of these cells and suggest that appropriate temporal delivery of
phosphate to ATDC5 cells in 3D cultures represents a rapid model for mechanistic
studies into the effects of exogenous cues on chondrogenic differentiation,
chondrocyte maturation, and matrix mineralization.
PMID- 28511054
TI - Synthesis and in vitro anticancer activity of new 2-thioxo-oxazolidin-4-one
derivatives.
AB - BACKGROUND: Oxazolidinones derivatives exhibit different biological properties,
including anticancer activity. This work aimed to investigate the anticancer
potential of five novel 2-Thioxo-oxazolidin-4-one derivatives. METHODS:
Cytotoxicity assays were performed in human peripheral blood mononuclear cells
(PBMCs) from healthy individuals and seven tumor cell lines. Apoptosis detection
and cell cycle were evaluated by flow cytometry and the expression of genes
involved in cell death processes by Real-Time PCR. RESULTS: All oxazolinedione
derivatives were not cytotoxic in PBMCs. NB-5 showed the best results in cancer
cells, inhibiting the growth of all tumor cell lines tested. NB-4 exhibited the
highest cytotoxicity in Jurkat cells (IC50=15.19MUM) and NB-3 showed better
anticancer effects in HL-60 (17.84MUM). Only NB-4 significantly induced apoptosis
in acute leukemia cells (p=0.001). All compounds caused a significant increase in
expression of pro-apoptotic gene BID (p<0.05) and BECN1 (p<0.05). NB-3
significantly modulated the expression of RIPK3 (p=0.02) and DDIT3 (p=0.014),
while NB-2 induced an increase of CDKN1A (p=0.03) and NB-4 induced PPARgamma gene
(p=0.0006). CONCLUSION: NB-5 showed antitumor effects in solid and hematopoietic
cancer cells, while other derivatives produced higher activity against
hematopoietic cells. In acute leukemia cells, oxazolidinone derivatives modulated
the expression of genes involved in apoptosis, ER stress, necroptosis and
inflammation.
PMID- 28511055
TI - Professional midwifery in Guatemala: A qualitative exploration of perceptions,
attitudes and expectations among stakeholders.
AB - BACKGROUND: Despite recommendations that women give birth with a skilled birth
attendant (SBA), 70% of births in Guatemala occur outside health facilities with
informally trained traditional birth attendants (TBAs). To increase SBA in rural,
indigenous communities, a professional midwifery school accredited by the
government is scheduled to open in 2017. Drawing from Filby's model on barriers
to the successful integration of professional midwifery into health systems, this
paper aims to identify threats - and facilitators-toward professional midwifery's
re-introduction in Guatemala. METHODS: To elucidate perceptions, attitudes and
expectations towards professional midwifery, qualitative, in-depth interviews
were conducted with 32 physicians, nurses, and TBAs in six health centers and
with key decision makers and professional midwives (PMs) in Guatemala City. We
conducted open and axial coding in Atlas.ti and performed normative comparisons
of participants' attitudes, perceptions, and expectations with the National
Vision for professional midwifery and relative comparisons within and across
disciplinary subgroups. RESULTS: Unprompted, physicians, nurses and TBAs were
unable to correctly define professional midwifery. Yet, when professional
midwifery was defined for them, they expressed willingness to work with PMs,
seeing them as a needed human resource, instrumental in providing intercultural
care and strengthening facility relationships with TBAs. Some stakeholders
anticipated resistance toward PMs due to provider turf issues. Notable
differences in expectations among all groups included ideas for supervision of
and by the PMs and the PM's role in monitoring women and conducting births in
communities alongside TBAs. CONCLUSIONS: Facilitators to professional midwifery's
success include national political will, stakeholders' uniformity of vision, and
the potential for improved intercultural care. Barriers are mostly professional
in nature, including impediments to autonomous practice by PMs, hierarchical
challenges, and turf issues. A specific road map addressing the identified
barriers is needed for professional midwifery to succeed in reducing maternal
health disparities in Guatemala.
PMID- 28511057
TI - Mapping smokeless powder residue on PVC pipe bomb fragments using total
vaporization solid phase microextraction.
AB - Quantitating post-blast explosive residue is not a common practice in crime labs
as it is typically not legally relevant. There is value in quantitation, however,
if the distribution of residues on Improvised Explosive Devices (IEDs) can help
guide future sample collection and/or method development. Total vaporization
solid phase microextraction gas chromatography mass spectrometry (TV-SPME/GC/MS)
was used to quantify residues of double-base smokeless powder (DBSP), which
includes nitroglycerin (NG), diphenylamine (DPA), and ethyl centralite (EC) on
post-blast PVC pipe bomb fragments. The analytical method could separate the
three constituents in under 5min with a detection limit under 1ppb, which
demonstrates high throughput while maintaining high sensitivity. The method was
optimized for nitroglycerin, as it is the most indicative of DBSP. The average
mass of nitroglycerin recovered from an entire PVC device was 1.0mg. The average
mass of diphenylamine recovered was much lower (24MUg) and only one device had
detectable levels of EC. The typical concentration of NG on any given fragment
was approximately 15-30ppm (MUg NG/g fragment). However, there was no correlation
between the mass of a fragment and the mass of residue upon it. Instead, the
residue was distributed such that the highest concentration of residues was found
on end cap fragments.
PMID- 28511058
TI - Stability behavior of antiretroviral drugs and their combinations. 7: Comparative
degradation pathways of lamivudine and emtricitabine and explanation to their
differential degradation behavior by density functional theory.
AB - The interest in this study was to establish comparative degradation behavior of
lamivudine (3TC) and emtricitabine (FTC) under solution and solid state stress
conditions. Structurally, the two drugs differ only in terms of additional
fluorine at 5 position in FTC. Along with the known degradation products of both
the drugs, one additional degradation product was observed in each case, which
was characterized by mass spectrometry. Both the drugs degraded via the same
route, but at a differential rate in acid, base and oxidative stress conditions.
The variable rate of degradation in acid and base conditions was justified by the
application of density functional theory (DFT).
PMID- 28511056
TI - Elimination of Schistosoma mansoni in infected mice by slow release of
artemisone.
AB - The current treatment of schistosomiasis is based on the anti-helminthic drug
praziquantel (PZQ). PZQ affects only the adult stages of schistosomes. In
addition, resistance to PZQ is emerging. We suggest a drug, which could serve as
a potential alternative or complement to PZQ, and as a means of treating
infections at earlier, pre-granuloma stage. Derivatives of the peroxidic
antimalarial drug artemisinin have been indicated as alternatives, because both
plasmodia and schistosomes are blood-feeding parasites. The mechanism of action
of artemisinins is related to oxidative effects of the artemisinins on
intracellular reductants leading to formation of cytotoxic reactive oxygen
species. We used artemisone, which has improved pharmacokinetics and anti
plasmodial activity, and reduced toxicity compared to other artemisinins in
clinical use against malaria. We infected adult mice by subcutaneous injection of
S. mansoni cercariae (about 200) and treated them at various times post infection
by the following methods: i. artemisone suspension administered by gavage (400
450 mg/kg); ii. subcutaneous injection of a gel containing a known concentration
of artemisone (115-120 mg/kg); iii. subcutaneous insertion of the drug
incorporated in a solid polymer (56-60 mg/kg); iv. intraperitoneal injection of
the drug solubilized in DMSO (115-120 mg/kg). Drug administration in polymers was
performed to enable slow release of the artemisone that was verified in vivo and
in vitro bioassays using drug-sensitive malaria parasites. We found superior
strong anti-schistosome effects up to a total reduction of worm number, mainly
following repetitive treatments with the drug absorbed in the polymers (73.1% and
95.9% reduction in mice treated with artemisone in gel 7 and 14, and 21, 28 and
35 days post infection, respectively). The results indicate that artemisone has a
potent anti-schistosome activity. Its main importance in this context is its
effectiveness in treating hosts harboring juvenile schistosomes, before egg
deposition and induction of deleterious immune responses.
PMID- 28511059
TI - Development and validation of a rapid reversed-phase HPLC method for the
quantification of monoclonal antibody bevacizumab from polyester-based
nanoparticles.
AB - Bevacizumab is a powerful human monoclonal antibody approved worldwide for
treatment of several types of cancer and ocular diseases due to its potential as
antiangiogenic drug. Nowadays, in order to improve the monoclonal antibody-based
therapy, attempts have been focused in the formulation of these biomacromolecules
into nanoparticles. Thus, the aim of this work was to develop and validate a
reversed-phase high-performance liquid chromatography with fluorescence detection
method for the determination of bevacizumab from nanoparticulate systems,
according to the International Conference on Harmonization guidelines.
Chromatographic analysis were performed on a RP-C8 column with a mobile phase
composed by water-0.1% (v/v) TFA and acetonitrile-0.1% (v/v) TFA in gradient mode
at a flow rate of 1mLmin-1. Results showed that the proposed method is specific,
linear in the range of 10-100MUgmL-1 (r2=0.9997), accurate (recovery rate
100.50+/-0.85%), precise at the intraday and inter-day (relative standard
deviation less than 1.79%) and robust. The detection and quantification limits
were calculated by specific linear calibration curve with less concentrated
standard (range of 1-20MUgmL-1). The LOD was 2.16MUgmL-1 and LOQ was 6.55MUgmL-1.
This method was also successfully used, for the first time, to quantify and
compare the content of bevacizumab encapsulated into poly(lactic-co-glycolic
acid)-based nanoparticles before and after lyophilization.
PMID- 28511060
TI - A comparison study on RNase A oligomerization induced by cisplatin, carboplatin
and oxaliplatin.
AB - Cisplatin (CDDP) can form interprotein cross-links, leading to the formation of
platinated oligomers. A dimer, a trimer and higher oligomers of bovine pancreatic
ribonuclease (RNase A) obtained upon reaction with CDDP in 1:10 protein to metal
ratio at 37 degrees C have been previously characterized. Here, we verify the
ability of carboplatin and oxaliplatin to induce RNase A oligomerization under
the same experimental conditions. The amount of formed RNase A oligomers was
compared with that obtained in the reaction of the protein with CDDP. Among the
three anticancer agents, CDDP is the most reactive and the most effective in
inhibiting the ribonucleolytic activity of the protein. Oxaliplatin is the least
potent oligomerization agent. Biophysical characterizations of structure and
stability of platinated dimers formed in the presence of carboplatin and
oxaliplatin suggest that they have a similar thermal stability and are more prone
to dissociation than the corresponding dimer obtained with CDDP. Oligomers
obtained in the presence of carboplatin are the most active. X-ray structures of
the monomeric adducts that RNase A forms with the three drugs provide a rational
basis to explain the different effects of the three anticancer agents on
enzymatic activity and protein aggregation. Although platinated oligomers of
RNase A formed upon reaction with CDDP, carboplatin and oxaliplatin retain a
residual ribonuclease activity, they do not show cytotoxic action, suggesting
that protein aggregation processes induced by Pt-based drugs can represent a
collateral drawback, which affects the functional state of protein targets and
reduces the efficacy of Pt-based drug treatment.
PMID- 28511061
TI - Uptake of Ga-curcumin derivatives in different cancer cell lines: Toward the
development of new potential 68Ga-labelled curcuminoids-based radiotracers for
tumour imaging.
AB - Thanks to the ability to suppress the proliferation and to kill tumour cells,
several studies have shown the anti-cancer effects of curcumin (CUR) and its
derivatives, i.e. diacetylcurcumin (DAC) and bis-dehydroxycurcumin (bDHC). This
study is focused onto the development of curcuminoid complexes with gallium-68
employed as potential new radio-labelled probes to detect neoplastic tissues
through imaging techniques such as positron emission tomography. To this purpose,
the uptake of three Ga-curcuminoid complexes, namely Ga(CUR)2+, Ga(DAC)2+,
Ga(bDHC)2+, by various tumour cell lines was compared with the uptake of the same
compounds by normal human lymphocytes by flow cytometry using the intrinsic
fluorescence of the curcuminoids. Ga(CUR)2+, and particularly Ga(DAC)2+, showed a
higher uptake by colorectal carcinoma (HT29) and lymphoma (K562) cell lines than
lymphocytes, while the uptake of Ga(bDHC)2+ was higher in lymphocytes than in all
the other cell lines. Based on the fluorescence data, Gallium-68 labelled
complexes were then tested in HT29 cell line. 68Ga(DAC)2+ showed the highest
uptake by HT29 cells (higher internalization with a lower externalization) and
the highest affinity. The obtained results are promising and the findings foster
further investigation on the development of curcumin-metal-based
radiopharmaceuticals.
PMID- 28511062
TI - Structure-activity relationship between Zn2+-chelated alkylated poly(1
vinylimidazole) and gene transfection.
AB - The structure-activity relationship between Zn2+-chelated alkylated poly(1
vinylimidazole) (PVIm) and gene transfection has been demonstrated. From a
chemical structure perspective, ethylated PVIm (PVIm-Et) chelated the most Zn2+
ions compared to methylated PVIm (PVIm-Me) and butylated PVIm (PVIm-Bu). The
resulting Zn2+-chelated PVIm-Et formed more stable complexes with plasmid DNA
complex than non-chelated PVIm-Et. From a biological activity perspective, the
Zn2+-chelated PVIm-Et delivered the highest amount of Zn2+ ions inside the cell,
corresponding to the highest gene transfection. These results suggest that PVIm
Et is the optimal sequence for the chelation of Zn2+ ions to enhance the gene
transfection activity. The structure-activity relationship in this study is
expected to offer a unique molecular design for drug/gene delivery systems.
PMID- 28511063
TI - Competitive reactions among glutathione, cisplatin and copper-phenanthroline
complexes.
AB - A large number of cancers are treated with cisplatin (CDDP). However, its use is
limited by drug resistance, which is often related to intracellular levels of
thiol-containing molecules such as glutathione (GSH). The role of GSH in
cisplatin-resistant cancer cells is still unclear. GSH may form adducts with CDDP
which results in the deactivation of the drug, and, actually, a high
intracellular level of GSH was observed in some cisplatin-resistant cancers. To
overcome drug resistance, CDDP is often administered in combination with one or
more drugs to exploit a possible synergistic effect. In previous studies, we
observed that the sensitivity to CDDP of leukemic and ovarian cisplatin-resistant
cancer cells was restored in the presence of [Cu(phen)2(H2O)](ClO4)2 (C0) (phen
is 1,10-phenathroline). In order to clarify the possible interactions between GSH
and CDDP, the reactivity and competitive reactions among CDDP, C0 and GSH in
binary and ternary mixtures were studied. The investigation was extended also to
[Cu(phen)(H2O)2(ClO4)2] (C10) and GSSG, the oxidized form of GSH. It was observed
that CDDP was able to react with the studied copper complexes and with GSH or
GSSG. However, in mixtures containing CDDP, GSH or GSSG and C0 or C10, only
copper-glutathione complexes were detected, while no platinum-glutathione adducts
were found.
PMID- 28511064
TI - Design, synthesis and evaluation of anticancer activity of ruthenium (II)
polypyridyl complexes.
AB - A new ligand PFPIP (PFPIP=2-(2,3,4,5,6-pentafluorophenyl)[4,5-f]imadazo
[1,10]phenanthroline) and its four ruthenium(II) polypyridyl complexes
[Ru(NN)2(PFPIP)](ClO4)2 (NN=dmb: 4,4'-dimethyl-2,2'-bipyridine, 1; bpy: 2,2'
bipyridine, 2; phen: 1,10-phenanthroline, 3; dmp: 2,9-dimethyl-1,10
phenanthroline, 4) were synthesized and characterized by elemental analysis, IR,
1H NMR, 13C NMR and ESI-MS. The cytotoxic activity in vitro of the ligand and
complexes toward BEL-7402, A549, HeLa, HepG2 and MG-63 cell lines was evaluated
using MTT method (MTT=(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide). Complexes 1, 3 and 4 show moderate cytotoxic effect on the cell growth
in BEL-7402 cells with IC50 values of 32.1+/-0.9, 37.9+/-1.7 and 42.1+/-3.0MUM,
respectively. The apoptosis in BEL-7402 cell was investigated with AO/EB and
Hoechst 33,258 staining methods. The autophagy in BEL-7402 cell induced by
complexes was assayed using MDC staining cell nuclei. The cell invasion, reactive
oxygen species (ROS), mitochondrial membrane potential, cell cycle arrest,
cellular uptake, comet assay and wound healing were studied under a fluorescent
microscope. The complexes can cause autophagy and inhibit the cell invasion, and
increase the ROS levels and induce a decrease in the mitochondrial membrane
potential. The expression of the proteins related with apoptosis induced by the
complexes was assayed by western blot analysis.
PMID- 28511065
TI - Quantifying the brain's sheet structure with normalized convolution.
AB - The hypothesis that brain pathways form 2D sheet-like structures layered in 3D as
"pages of a book" has been a topic of debate in the recent literature. This
hypothesis was mainly supported by a qualitative evaluation of "path
neighborhoods" reconstructed with diffusion MRI (dMRI) tractography.
Notwithstanding the potentially important implications of the sheet structure
hypothesis for our understanding of brain structure and development, it is still
considered controversial by many for lack of quantitative analysis. A means to
quantify sheet structure is therefore necessary to reliably investigate its
occurrence in the brain. Previous work has proposed the Lie bracket as a
quantitative indicator of sheet structure, which could be computed by
reconstructing path neighborhoods from the peak orientations of dMRI orientation
density functions. Robust estimation of the Lie bracket, however, is challenging
due to high noise levels and missing peak orientations. We propose a novel method
to estimate the Lie bracket that does not involve the reconstruction of path
neighborhoods with tractography. This method requires the computation of
derivatives of the fiber peak orientations, for which we adopt an approach called
normalized convolution. With simulations and experimental data we show that the
new approach is more robust with respect to missing peaks and noise. We also
demonstrate that the method is able to quantify to what extent sheet structure is
supported for dMRI data of different species, acquired with different scanners,
diffusion weightings, dMRI sampling schemes, and spatial resolutions. The
proposed method can also be used with directional data derived from other
techniques than dMRI, which will facilitate further validation of the existence
of sheet structure.
PMID- 28511066
TI - Deep image mining for diabetic retinopathy screening.
AB - Deep learning is quickly becoming the leading methodology for medical image
analysis. Given a large medical archive, where each image is associated with a
diagnosis, efficient pathology detectors or classifiers can be trained with
virtually no expert knowledge about the target pathologies. However, deep
learning algorithms, including the popular ConvNets, are black boxes: little is
known about the local patterns analyzed by ConvNets to make a decision at the
image level. A solution is proposed in this paper to create heatmaps showing
which pixels in images play a role in the image-level predictions. In other
words, a ConvNet trained for image-level classification can be used to detect
lesions as well. A generalization of the backpropagation method is proposed in
order to train ConvNets that produce high-quality heatmaps. The proposed solution
is applied to diabetic retinopathy (DR) screening in a dataset of almost 90,000
fundus photographs from the 2015 Kaggle Diabetic Retinopathy competition and a
private dataset of almost 110,000 photographs (e-ophtha). For the task of
detecting referable DR, very good detection performance was achieved: Az=0.954 in
Kaggle's dataset and Az=0.949 in e-ophtha. Performance was also evaluated at the
image level and at the lesion level in the DiaretDB1 dataset, where four types of
lesions are manually segmented: microaneurysms, hemorrhages, exudates and cotton
wool spots. For the task of detecting images containing these four lesion types,
the proposed detector, which was trained to detect referable DR, outperforms
recent algorithms trained to detect those lesions specifically, with pixel-level
supervision. At the lesion level, the proposed detector outperforms heatmap
generation algorithms for ConvNets. This detector is part of the Messidor(r)
system for mobile eye pathology screening. Because it does not rely on expert
knowledge or manual segmentation for detecting relevant patterns, the proposed
solution is a promising image mining tool, which has the potential to discover
new biomarkers in images.
PMID- 28511069
TI - Ischaemic preconditioning - Current knowledge and potential future applications
after 30 years of experience.
AB - Ischaemic preconditioning (IPC) phenomenon has been known for thirty years.
During that time several studies showed that IPC provided by brief ischaemic and
reperfusion episodes prior to longer ischaemia can bestow a protective effect to
both preconditioned and also remote organs. IPC affecting remote organs is called
remote ischaemic preconditioning. Initially, most IPC studies were focused on
enhancing myocardial resistance to subsequent ischaemia and reperfusion injury.
However, preconditioning was found to be a universal phenomenon and was observed
in various organs and tissues including the heart, liver, brain, retina, kidney,
skeletal muscles and intestine. Currently, there are a lot of simultaneous
studies are underway aiming at finding out whether IPC can be helpful in
protecting these organs. The mechanism of local and remote IPC is complex and not
well known. Several triggers, intracellular pathways and effectors, humoral,
neural and induced by genetic changes may be considered potential pathways in the
protective activity of local and remote IPC. Local and remote IPC mechanism may
potentially serve as heart protection during cardiac surgery and may limit the
infarct size of the myocardium, can be a strategy for preventing the development
of acute kidney injury development and liver damage during transplantation, may
protect the brain against ischaemic injury. In addition, the method is safe, non
invasive, cheap and easily applicable. The main purpose of this review article is
to present new advances which would help to understand the potential mechanism of
IPC. It also discusses both its potential applications and utility in clinical
settings.
PMID- 28511067
TI - A fuzzy logic-based tool to assess beef cattle ranching sustainability in complex
environmental systems.
AB - One of the most relevant issues in discussion worldwide nowadays is the concept
of sustainability. However, sustainability assessment is a difficult task due to
the complexity of factors involved in the natural world added to the human
interference. In order to assess the sustainability of beef ranching in complex
and uncertain tropical environment systems this paper describes a decision
support system based on fuzzy rule-approach, the Sustainable Pantanal Ranch
(SPR). This tool was built by a set of measurements and indicators integrated by
fuzzy logic to evaluate the attributes of the three dimensions of sustainability.
Indicators and decision rules, as well as scenario evaluations, were obtained
from workshops involving multi-disciplinary team of experts. A Fuzzy Rule-Based
System (FRBS) was developed to each attribute, dimension and general index. The
essential parts of the FRBS are the knowledge database, rules and the inference
engine. The FuzzyGen and WebFuzzy tools were developed to support the FRBS and
both showed efficiency and low cost for digital applications. The results of each
attribute, dimension and index were presented as radar graphs, showing the
individual value (0-10) of each indicator. In the validation process using the
WebFuzzy, different combinations of indicators were made for each attribute index
to show the corresponding output, and which confirm the feasibility and usability
of the tool.
PMID- 28511070
TI - Impact of exaggerated blood pressure response in normotensive individuals on
future hypertension and prognosis: Systematic review according to PRISMA
guideline.
AB - PURPOSE: Arterial hypertension (aHT) is the leading risk factor for morbidity and
mortality worldwide. Blood pressure (BP) deviation at rest is well defined and
accompanies risk for cardiovascular events and cardiovascular mortality. A
growing body of evidence emphasises that an exaggerated blood pressure response
(EBPR) in cardiopulmonary exercise testing (CPET) could help to identify
seemingly cardiovascular healthy and normotensive subjects, who have an increased
risk of developing aHT and cardiovascular events in the future. MATERIALS AND
METHODS: The PubMed online database was searched for published studies reporting
exercise-related BP and both the risk of aHT and cardiovascular events in the
future. RESULTS: We identified 18 original studies about EBPR in CPET, which
included a total of 35,151 normotensive individuals for prediction of new onset
of aHT in the future and 11 original studies with 43,012 enrolled subjects with
the endpoint of cardiovascular events in the future. Although an EBPR under CPET
is not well defined, a large number of studies emphasise that EBPR in CPET is
associated with both new-onset aHT and cardiovascular events in the future.
CONCLUSIONS: A growing number of studies support the hypothesis that EBPR in CPET
may be a diagnostic tool to identify subjects with an elevated risk of developing
aHT and cardiovascular events in the future.
PMID- 28511068
TI - Biotechnology and the transformation of vaccine innovation: The case of the
hepatitis B vaccines 1968-2000.
AB - The approval, from 1986, of a series of recombinant hepatitis B vaccines was a
landmark both in the growth of biotechnology and in the development of the
vaccine innovation system. In this paper, we show how the early development of
the hepatitis B vaccines was shaped by a political and economic context that
newly favoured commercialisation of academic research, including the
appropriation and management of intellectual property; we elucidate the
contingent interests and motivations that led new biotechnology companies and
established pharmaceutical businesses to invest in developing recombinant
vaccines specifically against hepatitis B; and we show how these and other
factors combined to make those vaccines an unexpected commercial success.
Broadening the scope of our analysis to include not just North America and Europe
but also low- and middle-income countries, we show how the development of the
hepatitis B vaccines facilitated the emergence of a two-tier innovation system
structured by tensions between the demands for commercial profitability on the
one hand, and the expectation of public health benefit for low- and middle-income
countries on the other.
PMID- 28511071
TI - Effects of gamma-radiation on cell growth, cell cycle and promoter methylation of
22 cell cycle genes in the 1321NI astrocytoma cell line.
AB - PURPOSE: DNA damage caused by radiation initiates biological responses affecting
cell fate. DNA methylation regulates gene expression and modulates DNA damage
pathways. Alterations in the methylation profiles of cell cycle regulating genes
may control cell response to radiation. In this study we investigated the effect
of ionizing radiation on the methylation levels of 22 cell cycle regulating genes
in correlation with gene expression in 1321NI astrocytoma cell line. METHODS:
1321NI cells were irradiated with 2, 5 or 10Gy doses then analyzed after 24, 48
and 72h for cell viability using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazoliu bromide) assay. Flow cytometry were used to study the effect
of 10Gy irradiation on cell cycle. EpiTect Methyl II PCR Array was used to
identify differentially methylated genes in irradiated cells. Changes in gene
expression was determined by qPCR. Azacytidine treatment was used to determine
whether DNA methylation affectes gene expression. RESULTS: Our results showed
that irradiation decreased cell viability and caused cell cycle arrest at G2/M.
Out of 22 genes tested, only CCNF and RAD9A showed some increase in DNA
methylation (3.59% and 3.62%, respectively) after 10Gy irradiation, and this
increase coincided with downregulation of both genes (by 4 and 2 fold,
respectively). TREATMENT: with azacytidine confirmed that expression of CCNF and
RAD9A genes was regulated by methylation. CONCLUSIONS: 1321NI cell line is highly
radioresistant and that irradiation of these cells with a 10Gy dose increases DNA
methylation of CCNF and RAD9A genes. This dose down-regulates these genes,
favoring G2/M arrest.
PMID- 28511072
TI - Pro-inflammatory cytokines associated with clinical severity of dry eye disease
of patients with depression.
AB - PURPOSE: The aim of this study was to assess the correlation of inflammatory
cytokines levels in tears with severity of dry eye disease in a cohort of
patients with depression. MATERIAL AND METHODS: Tear fluid samples were collected
from 32 patients with depression treated with antidepressants, and 34 healthy
subjects. Cytokines were assessed by ELISA. All the subjects completed the Beck
Depression Inventory and performed the ophthalmic examination, including dry eye
tests. RESULTS: The tear fluid levels of IL-6, IL-17 and TNF-alpha in depressive
patients were higher than in controls. The clinical severity of dry eye disease
correlated significantly with the IL-17 and TNF-alpha levels. CONCLUSIONS: Our
results suggest a crucial role of inflammatory cytokines, especially IL-17 and
TNF-alpha, in the development of severe dry eye disease in patients with
depression. Clarification of the role pro-inflammatory cytokines in the
pathogenesis of ocular findings in depressive patients may be useful in
establishing immunotherapeutic strategies for this disease.
PMID- 28511074
TI - Charcot arthropathy of the knee after unsuccessful spinal stenosis surgery: A
case report.
AB - INTRODUCTION: Charcot arthropathy was first described in 1868 by Jean Martin
Charcot as a progressive and destructive joint disease. Diabetes, polyneuropathy,
syphilis, syrengomyelia and chronic alcoholism are the main causes of the
disease. In this study we present a Charcot arthropathy of the knee seen after
unsuccessful spinal stenosis surgery. PRESENTATION OF CASE: We report here a case
of 62 years old patient with Charcot arthropathy at her left knee developed one
year after spinal stenosis surgery. The patient's knee joint was already beyond
the fragmentation and coalescence stages at the moment of physical examination.
Patient had already been treated for Charcot foot four years before spinal
surgery. Because of an unsuccessful spinal surgery, proximal migration of the
level of the sensorineural loss negatively affected the polyneuropathy and
eventually resulted in Charcot knee joint in a short period of time. DISCUSSION:
However, the etiology of the neuropathic arthropathy hasn't been well described
yet, it is usually seen at patients with diabetes mellitus as a long-term
complication with or without polyneuropathy. In addition to the spinal canal
pathologies, it is reported that Charcot arthropathy can be seen even after
spinal anesthesia procedures. CONCLUSION: In conclusion, spinal procedures should
be applied with extra caution on the patients with polyneuropathy or any
neuropathic arthropathy. It should be remembered that it is possible to encounter
unexpected complications such as proximally migration of the level of
sensorineural loss and progression of the actual disease after spinal procedures
of these patients.
PMID- 28511073
TI - Preparation and evaluation of L- and D-5-[18F]fluorotryptophan as PET imaging
probes for indoleamine and tryptophan 2,3-dioxygenases.
AB - : Indoleamine and tryptophan 2,3-dioxygenases (IDO1 and TDO2) are pyrrolases
catalyzing the oxidative cleavage of the 2,3-double bond of L-tryptophan in
kynurenine pathway. In the tumor microenvironment, their increased activity
prevents normal immune function, i.e. tumor cell recognition and elimination by
cytotoxic T-cells. Consequently, inhibition of the kynurenine pathway may enhance
the activity of cancer immunotherapeutics by reversing immune dysfunction. We
sought to investigate the properties of radiolabeled 5-[18F]fluorotryptophan with
respect to its ability for measuring IDO1 and TDO2 activity by positron emission
tomography (PET). RESULTS: L-5-[18F]fluorotryptophan and D-5
[18F]fluorotryptophan were synthesized by Cu(I) catalyzed
[18F]fluorodeboronylation of Boc/tBu protected precursors in moderate yields
(1.5+/-0.6%) sufficient for pre-clinical studies. The specific activity of the
product was 407-740GBq/MUmol, radiochemical purity >99% and enantiomeric excess
90-99%. Enzymatic assay confirmed that L-5-fluorotryptophan is an IDO1 and TDO2
substrate whereas the D-isomer is not. In-vitro cell uptake experiments using
CT26 cells with doxycycline-induced overexpression of human-IDO1 and human-TDO2
revealed an elevated cell uptake of L-5-[18F]fluorotryptophan upon induction of
IDO1 or TDO2 enzymes compared to baseline; however, the uptake was observed only
in the presence of low L-tryptophan levels in media. PET imaging experiments
performed using tumor bearing mouse models expressing IDO1 at various levels
(CT26, CT26-hIDO1, 17082A, 17095A) showed tumor uptake of the tracer elevated up
to 8%ID/g; however, the observed tumor uptake could not be attributed to IDO1
activity in the tumor tissue. The metabolism of L- and D- isomers was markedly
different in vivo, the D-isomer was excreted by a combination of hepatobiliary
and renal routes, the L-isomer underwent extensive metabolism to [18F]fluoride.
CONCLUSION: The observed in vivo tumor uptake of the tracer could not be
attributed to IDO1 or TDO2 enzyme activity in the tumor, presumably due to
competition with endogenous tryptophan as well as rapid tracer metabolism.
PMID- 28511075
TI - Using endoscopy to minimize the extent of resection in the management of giant
GISTs of the stomach.
AB - INTRODUCTION: The stomach is the most common site for GISTs. Wide local resection
to achieve negative margins is the standard of care. Giants GISTs requiring
extensive resection are usually managed with neo-adjuvant therapy followed by
partial or total gastrectomy. PRESENTATION OF CASE: We present a case report of a
giant GIST on the lesser curvature of the stomach. Neo-adjuvant therapy was
administered. Intra-operative endoscopy was used to reduce the extent of gastric
resection. DISCUSSION: Simultaneous intra-operative endoscopy demonstrated a 2mm
fistula on the lesser curvature of the stomach. A stapler was used to encompass
the mass and the fistulous opening. A frozen-section showed clear margins and the
endoscope was used to perform an air-leak test. The patient recovered without
complications. CONCLUSION: Intra-operative endoscopy can reduce the extent of
gastric resection for large GISTs while maintaining the oncologic principles of
negative margins and minimal tissue handling.
PMID- 28511076
TI - The tissue distribution, metabolism and hepatotoxicity of benzoylurea pesticides
in male Eremias argus after a single oral administration.
AB - Benzoylurea pesticides (BPUs) are widely used to control the locust, but the
toxicokinetics and hepatotoxicity of BPUs in lizards have not been investigated.
In this study, the tissue distribution, metabolism and liver toxicity of
diflubenzuron and flufenoxuron were assessed in the Eremias argus following a
single oral exposure. Diflubenzuron preferred to accumulate in the fat and brain
(>1.0 mg kg-1) and was rapidly eliminate in other tissues. In the liver, 4
chloroaniline was one of diflubenzuron metabolites, although with a concentration
less than 0.05% of the accumulated diflubenzuron. No significant difference was
observed in the liver histopathology between the control and diflubenzuron
exposure group. The expressions of Cyp1a and Ahr gene which control the cell
apoptosis were also equal to the control level. After flufenoxuron exposure,
biomodal phenomenon was observed in the liver, skin, brain, gonad, kidney, heart
and blood circulation was an important route for the flufenoxuron penetration.
The concentrations of flufenoxuron in all tissues were greater than 1.0 mg kg-1
at 168 h. The excretion of flufenoxuron in the faeces was 1.5 fold higher than
diflubenzuron. The hepatocytes in the flufenoxuron treated group showed
vacuolation of cytoplasm and decreased nucleus. In addition, the Cyp1a and Ahr
genes were significantly up-regulated in the flufenoxuron exposure group. These
results suggested that the higher hepatotoxicity of flufenoxuron may be
attributed to the higher residual level in the lizard tissues and the Cyp1a and
Ahr genes can serve as biomarkers to assess the liver toxicity.
PMID- 28511077
TI - Clinical and laboratory parameters predicting a requirement for the reevaluation
of growth hormone status during growth hormone treatment: Retesting early in the
course of GH treatment.
AB - OBJECTIVE: We aimed to define the predictive criteria, in the form of specific
clinical, hormonal and radiological parameters, for children with growth hormone
deficiency (GHD) who may benefit from the reevaluation of GH status early in the
course of growth hormone (GH) treatment. DESIGN AND METHODS: Two hundred sixty
five children with growth hormone deficiency were retested by GH stimulation at
the end of the first year of GH treatment. The initial clinical and laboratory
characteristics of those with a normal (GH>=10ng/ml) response and those with a
subnormal (GH<10ng/ml) response were compared to predict a normal GH status
during reassessment. RESULTS: Sixty-nine patients (40.6%) out of the 170 patients
with isolated growth hormone deficiency (IGHD) had a peak GH of >=10ng/ml during
the retest. None of the patients with multiple pituitary hormone deficiency
(MPHD) had a peak GH of >=10ng/ml. Puberty and sex steroid priming in
peripubertal cases increased the probability of a normal GH response. Only one
patient with IGHD who had an ectopic posterior pituitary without stalk
interruption on MRI analysis showed a normal GH response during the retest.
Patients with a peak GH between 5 and 10ng/ml, an age at diagnosis of >=9years or
a height gain below 0.61 SDS during the first year of treatment had an increased
probability of having a normal GH response at the retest. CONCLUSION: Early
reassessment of GH status during GH treatment is unnecessary in patients who have
MPHD with at least 3 hormone deficiencies. Retesting at the end of the first year
of therapy is recommended for patients with IGHD who have a height gain of <0.61
SDS in the first year of treatment, especially those with a normal or
'hypoplastic' pituitary on imaging. Priming can increase the likelihood of a
normal response in patients in the pubertal age group who do not show overt signs
of pubertal development.
PMID- 28511078
TI - Performance of electro-osmotic dewatering on different types of sewage sludge.
AB - The feasibility of pressure-driven electro-dewatering (EDW) on sludge samples
taken after different biological processes, stabilisation methods or mechanical
dewatering techniques was assessed. First, the influence of potential values on
EDW of anaerobically and aerobically stabilised, mechanically dewatered, sludge
samples was investigated. Preliminary tests carried out by applying a constant
potential (10, 15 and 20V) in a lab-scale device confirmed the possibility to
reach a dry solid (DS) content of up to 42.9%, which corresponds to an increase
of 15% of the dry content in dewatered sludge without the application of the
electrical field. Dewatering increased with the applied potential but at the
expense of a higher energy consumption. A potential equal to 15V was chosen as
the best compromise for EDW performance, in terms of DS content and energy
consumption. Then, the influence of the mechanical dewatering was studied on
aerobically stabilised sludge samples with a lower initial DS content: the higher
initial water content led to a lower final DS content but with a considerable
reduction of energy consumption. Finally, the biological process, studied by
comparing sludge samples from conventional activated sludge and membrane
bioreactor processes, didn't evidence any influence on EDW. Experimental results
shown that DS obtained after mechanical dewatering, volatile solids and
conductivity are the main factors influencing EDW. Anaerobically digested sludge
reached the highest DS content, thanks to lower organic fraction.
PMID- 28511079
TI - Psychosocial stress and obesity among children residing in Kaunas City.
AB - INTRODUCTION: An unfavorable psychosocial environment has been associated with an
increased prevalence of obesity among children. However, the available evidence
on the association of low socioeconomic status and parent-child relationships
with childhood obesity is scarce. The aim of our study was to conduct a
simultaneous evaluation of the risks associated with pathological mother-child
relationships, education level, and overweight/obesity among 4-6 year-old
children. METHODS: This cross-sectional study included 1489 mother-child pairs
living in Kaunas city, Lithuania. The Parenting Stress Index was measured using
the Parent-Child Dysfunctional Interaction subscale. Children's
overweight/obesity was defined as the body mass index >=18kg/m2. Logistic
regression models as well as crude and adjusted odds ratios (OR) and their 95%
confidence intervals (CI) were used to indicate the strength of the associations
between childhood overweight/obesity, maternal education level, and psychosocial
stress. RESULTS: The percentage of children with overweight/obesity rose with an
increasing Parenting Stress Index score. The percentage of children with
overweight/obesity in the group of parents with better education and normal
mother-child relations was 6.0%, while in the group of less educated parents and
pathological mother-child relations, this percentage reached 13.9%. The
stratified multivariable model showed that, with reference to the group of better
educated parents and normal mother-child relations, lower education level and
pathological mother-child relations were statistically significant risk factors
for overweight/obesity in 4-6 year-old children, increasing the OR of
overweight/obesity (aOR: 2.43; 95% CI: 1.31-4.51). Pathological mother-child
relations and maternal smoking mediated the effect of low maternal education
level on children's BMI z-scores. CONCLUSION: Pathological mother-child
relations, lower parental education levels, and smoking may be predictors of
children's overweight/obesity. Measures oriented towards health behavior and
psychosocial stress management should be encouraged among parents in order to
decrease the risk of overweight/obesity in their children.
PMID- 28511081
TI - A novel ultrasonic surface machining tool utilizing elastic traveling waves.
AB - With the rapid development of modern industrial technology and high performance
technology products, ultra-precision machining technology becomes increasingly
important. However, joint clearance of kinematic pairs, lack of feeding accuracy
and overlarge contact stress still limit the further improvement of ultra
precision machining technology. In this study, a novel surface machining method
utilizing structural elastic waves was proposed, and a machining tool using the
piezoelectric actuating principle was presented for verifying the proposed
method. Two vibration modes with a phase shift of pi/2 in both space and time
domains are exited simultaneously in the elliptical motion of points on the
structural surface. By means of adjusting driving signal parameters, such as
frequency, voltage amplitude and phase shift, different machining performances
could be achieved. The configuration and working vibration modes of the proposed
machining tool were firstly calculated by the finite element method, and then the
optimal working frequency of the machining tool prototype was determined by
vibration characteristic experiments. At last, machining characteristic
experiments were conducted to validate the proposed machining method.
Experimental results showed that the minimum working contact force between the
machining tool and workpiece was 1N, and the chipped depth of 1.93MUm was
achieved at the same contact force after machining for 5min. And at the
conditions of the contact force of 6N, two driving voltages of 400Vpp with a
phase shift of pi/2, and machining time of 5min, the prototype could achieve to
machine the workpiece most efficiently and the roughness of the machined
workpiece surface could be reached approximating 0.20MUm. In conclusion, this
proposed machining method could achieve a good quality machined surface with low
residual stress and little damage by applying low contact force. Furthermore, it
also had the advantage of no joint clearance error due to no kinematic pair in
the structure, which improves the machining precision.
PMID- 28511082
TI - Nonlinear Lamb waves for fatigue damage identification in FRP-reinforced steel
plates.
AB - A nonlinear Lamb-wave-based method for fatigue crack detection in steel plates
with and without carbon fibre reinforcement polymer (CFRP) reinforcement is
presented in this study. Both numerical simulation and experimental evaluation
were performed for Lamb wave propagation and its interaction with a fatigue crack
on these two steel plate types. With the generation of the second harmonic, the
damage-induced wave nonlinearities were identified by surface-bonded
piezoelectric sensors. Numerical simulation revealed that the damage-induced wave
component at the second harmonic was slightly affected by the existence of CFRP
laminate, although the total wave energy was decreased because of wave leakage
into the CFRP laminate. Due to unavoidable nonlinearity from the experimental
environments, it was impractical to directly extract the time-of-flight of the
second harmonic for locating the crack. To this end, the correlation coefficient
of benchmark and signal with damage at double frequency in the time domain was
calculated, based on which an imaging method was introduced to locate the fatigue
crack in steel plates with and without CFRP laminates.
PMID- 28511080
TI - Cadmium and Alzheimer's disease mortality in U.S. adults: Updated evidence with a
urinary biomarker and extended follow-up time.
AB - Cadmium has been linked to impaired cognitive function in adults and may cause
behavioral, physiological and molecular abnormalities characteristic of
Alzheimer's disease (AD) in animals. Evidence linking cadmium and AD in humans is
limited, but supportive. In the most recent epidemiologic study, blood cadmium in
U.S. adults was positively associated with elevated AD mortality 7-13 years
later. The association between urinary cadmium - an arguably more appropriate
biomarker for studying chronic diseases - and AD mortality has not yet been
explored. Further study of cadmium and AD mortality in an independent population,
with longer follow-up, and stratified by sex is also needed. We sought to answer
these questions using the U.S. National Health and Nutrition Examination Survey
(NHANES) (1999-2006 cycles) and NHANES III (interviews in 1988-1994) datasets,
separately linked to AD mortality as of 2011. We used survey-weighted Cox
regression models predicting age at AD death and adjusted for race/ethnicity,
sex, smoking status, education and urinary creatinine. An interquartile range
(IQR; IQR=0.51ng/mL) increase in urinary cadmium was associated with 58% higher
rate of AD mortality (hazard ratio (HR)=1.58, 95% CI: 1.20, 2.09. p-value=0.0009,
mean follow-up: 7.5 years) in NHANES 1999-2006 participants. In contrast, in
NHANES III participants, an IQR (IQR=0.78ng/mL) increase in urinary cadmium was
not associated with AD mortality (HR=0.85, 95% CI: 0.63, 1.17, p-value=0.31, mean
follow-up: 13 years). Also in the NHANES III sample however, when the maximum
follow-up time was restricted to 12.7 years (i.e. the same as NHANES 1999-2006
participants) and urinary creatinine adjustments were not made, urinary cadmium
was associated with elevated AD mortality (HR=1.11, 95% CI: 1.02, 1.20, p
value=0.0086). Our study partially supported an association between cadmium and
AD mortality, but the sensitivity of results to follow-up time and creatinine
adjustments necessitate cautious interpretation of the association. Further
studies, particularly those on toxicological mechanisms, are required to fully
understand the nature of the "cadmium-AD mortality" association.
PMID- 28511084
TI - Examining ethnic inequalities in health and tenure in England: A repeated cross
sectional analysis.
AB - Ethnic minorities experience multiple inequalities across different domains
including health and tenure. Notwithstanding extensive research demonstrating a
clear connection between tenure and health, the relationship between health,
tenure and ethnicity is under-explored. In this paper, we examine ethnic
inequalities in health and tenure in England using cross-sectional census
microdata for 1991, 2001 and 2011. We find that ethnic inequalities in health
persist over time while the relationship between health and tenure varies between
ethnic groups. These results suggest that traditional explanations linking health
and tenure are not sufficient to adequately capture the myriad experiences of
different ethnic groups.
PMID- 28511083
TI - How do type and size of natural environments relate to physical activity
behavior?
AB - Natural environments (NE) are promoted as places that support physical activity
(PA), but evidence on PA distribution across various types and sizes of NE is
lacking. Accelerometers and GPS-devices measured PA of Dutch general population
adults aged 45-65 years (N=279). Five NE types were distinguished: 'parks',
'recreational area', 'agricultural green', 'forest & moorland', and 'blue space',
and four categories of size: 0-3, 3-7, 7-27, and >=27 ha. Modality (i.e.
spatially concentrated PA, walking, jogging, and cycling) and intensity (i.e.
sedentary behavior, LPA, and MVPA) of PA varied significantly between NE types.
Compared to parks, less sedentary behavior and walking but more spatially
concentrated PA was observed in recreational areas and green space. Cycling
levels were found to be significantly lower in recreational areas and forest &
moorland, but higher in blue space as compared to parks. Larger sized NE (>=7 ha)
were associated with higher levels of MVPA, walking, jogging and cycling. Insight
in which environments (according to type and size) facilitate PA, contributes to
the development of tailored PA promoting interventions with ensuing implications
for public health.
PMID- 28511085
TI - Development, implementation, and effects of an integrated web-based teaching
model in a nursing ethics course.
AB - BACKGROUND: Ethical competence, which is reflected in the ability to detect
ethical challenges in clinical situations and engage in deliberate thinking on
ethical actions, is one of the core competencies of nursing practice. PURPOSE:
The purpose of this study was to develop and implement an interactive situational
e-learning system, integrating nursing ethical decisions into a nursing ethics
course, and to evaluate the effects of this course on student nurses' ethical
decision-making competence. PROJECT DESIGN: The project was designed to be
carried out in two phases. In the first phase, an interactive situated e-learning
system was developed and integrated into the nursing ethics course. The second
phase involved implementing the course and evaluating its effects in a quasi
experimental study. The course intervention was designed for 2h per week over one
semester (18weeks). PARTICIPANTS: A total of 100 two-year technical college
nursing students in their second year of the program participated in the study,
with 51 in the experimental group and 49 in the control group. RESULTS: After
completing the course, the students in the experimental group showed significant
improvement in nursing ethical decision-making competence, including skills in
"raising questions," "recognizing differences," "comparing differences," "self
dialogue," "taking action," and "identifying the implications of decisions made,"
compared to their performance prior to the class. After controlling for factors
influencing learning effects, students in the experimental group showed
superiority to those in the control group in the competency of "recognizing
differences." The students in the experimental group reported that the course
pushed them to search for and collect information needed to resolve the ethical
dilemma. CONCLUSIONS: The interactive situational e-learning system developed by
our project was helpful in developing the students' competence in ethical
reasoning. The e-learning system and the situational teaching materials used in
this study may be applicable in nursing and related professional ethics courses.
PMID- 28511086
TI - Local endometrial injury in women with failed IVF undergoing a repeat cycle: A
randomized controlled trial.
AB - OBJECTIVE: To evaluate the effectiveness of local endometrial injury in women
undergoing in vitro fertilization (IVF) with at least one previous unsuccessful
attempt. STUDY DESIGN: Randomized controlled trial. Recruited women were
randomized into two groups. In group A (pipelle group), women underwent pipelle
biopsy twice in the luteal phase in the cycle prior to IVF. In group B (control),
women did not undergo any intervention prior to IVF. The primary outcome was
clinical pregnancy rate. The secondary outcomes included live birth, miscarriage,
multiple pregnancy and preterm delivery rates. RESULTS: One hundred and eleven
women were included in the study with 55 in the pipelle group and 56 in the
control arm. The baseline clinical characteristics were similar in both groups.
The clinical pregnancy rates were not significantly different between pipelle and
control group (34.09% vs. 27.65%; Odds ratio, OR 1.35, 95% confidence interval,
CI 0.55-3.30). The live birth (31.81% vs. 25.53%; OR 1.36, 95% CI 0.55-3.39),
multiple pregnancy (33.33% vs. 61.54%; OR 0.31, 95% CI 0.07-1.47), miscarriage
(6.66% vs. 7.69%; OR 0.86, 95% CI 0.05-15.23) and preterm delivery rates (35.71%
vs. 66.66%; OR 0.28, 95% CI 0.05-1.4) were also not significantly different
between the two groups. CONCLUSION: Current study did not find any improvement in
IVF success rates following endometrial injury in woman undergoing IVF after
previous failed attempt.
PMID- 28511087
TI - Optional use of CAM photosynthesis in two C4 species, Portulaca cyclophylla and
Portulaca digyna.
AB - Low levels of crassulacean acid metabolism (CAM) are demonstrated in two species
with C4 photosynthesis, Portulaca cyclophylla and P. digyna. The expression of
CAM in P. cyclophylla and P. digyna is facultative, i.e. optional. Well-watered
plants did not accumulate acid at night and exhibited gas-exchange patterns
consistent with C4 photosynthesis. CAM-type nocturnal acidification was
reversible in that it was induced following drought and lost when droughted
plants were rewatered. In P. cyclophylla, droughting was accompanied by a small
but discernible net uptake of CO2 during the dark, whereas in P. digyna, net CO2
exchange at night approached the CO2 compensation point but did not transition
beyond it. This report brings the number of known C4 species with a capacity for
expressing CAM to six. All are species of Portulaca. The observation of CAM in P.
cyclophylla and P. digyna is the first for species in the opposite-leaved (OL)
Portulacelloid-anatomy lineage of Portulaca and for the Australian clade therein.
The other four species are within the alternate-leaved (AL) lineage, in the
Atriploid-anatomy Oleracea and the Pilosoid-anatomy Pilosa clades. Studies of the
evolutionary origins of C4 and CAM in Portulaca will benefit from a more wide
range survey of CAM across its species, particularly in the C3-C4 intermediate
containing Cryptopetala clade.
PMID- 28511088
TI - Effects of increasing dietary organic selenium levels on meat fatty acid
composition and oxidative stability in growing rabbits.
AB - The effects of dietary organic selenium (Se) addition at 0.1, 0.5 and 2.5mg/kg
vs. an unsupplemented basal diet (BD) on performance, fatty acid (FA) composition
and oxidative stability were studied in muscle tissue of growing rabbits. Muscle
Se content increased (P<0.001) in a dose dependent manner with dietary Se
inclusion. Saturated FA (SFA) were affected linearly (P<0.05) and quadratically
(P<0.05) by dietary Se addition. Polyunsaturated FA (PUFA) increased linearly
(P<0.01) resulting in a linear increase in the PUFA:SFA ratio (P<0.01) with
dietary Se increment. Feeding 0.5mgSe/kg diet reduced malondialdehyde (MDA) and
oxygen radical absorbance capacity (ORAC) values in the muscle, whilst 2.5mgSe/kg
diet increased MDA concentrations and tended to increase ORAC values, likely
indicating oxidative stress. In conclusion, dietary Se supplementation at
0.5mg/kg improves meat FA composition and oxidative stability, whereas at
2.5mg/kg may induce pro-oxidant effects.
PMID- 28511089
TI - A computational assessment of representative sampling of soil gas using existing
groundwater monitoring wells screened across the water table.
AB - Representative sampling is of great importance to decision making regarding
contaminant site risks and remedial effectiveness. A focus here is whether
existing groundwater monitoring wells screened across the water table can be
sampled to yield representative indicators of soil gas composition. For the first
time, we provide multi-phase, multi-component computational simulations to
address this. We simulated high and low gas extractions rate strategies to sample
the gas phase over short and extended screening intervals across the water table.
We investigated the options against a field data set representative of typical
hydrocarbon vapour profiles, inclusive of major gases, oxygen and carbon dioxide.
We also evaluated the sampling options for uniform and non-uniform multi
component gasoline LNAPL distributions, including hazardous chemicals. Less
sensitivity to the sampling option was observed for depth-wise increasing
concentration profiles with a near-constant concentration across the screen.
Significant discrepancy between the ratio of different compounds in the sample
and in-situ (real) values was observed for high-rate gas extraction (particularly
for an extended-screen). Low-rate gas extraction provided satisfactory results
for all the scenarios. Shorter screening slightly improved the accuracy of this
option. Graphical representations are provided to allow assessment of the
applicability of each sampling option for various site conditions.
PMID- 28511090
TI - Inactivation of the KSRP gene modifies collagen antibody induced arthritis.
AB - The KH type splicing regulatory protein (KSRP) is a nucleic acid binding protein,
which negatively regulates the stability and/or translatability of many mRNA
species encoding immune-relevant proteins. As KSRP is expressed in immune cells
including T and B cells, neutrophils, macrophages and dendritic cells, we wanted
to analyze its importance for the development of autoimmune diseases. We chose
collagen antibody-induced arthritis (CAIA) as an appropriate autoimmune disease
mouse model in which neutrophils and macrophages constitute the main effector
cell populations. We compared arthritis induction in wild type (WT) and KSRP-/-
mice and paws were taken for histological sections and qPCR analysis.
Furthermore, we determined the frequencies of spleen immune cells by flow
cytometry. Cytokine levels in spleen cell supernatants were determined by
cytometric bead array analyses (CBA). After CAIA induction we unexpectedly
observed in WT animals much stronger swelling of the paws than in KSRP-/- mice.
In accordance, histological staining of paw sections of KSRP-/- animals revealed
much lower frequencies of infiltrating immune cells in the joints compared to WT
animals. Furthermore, CAIA-treatment resulted in reduced expression of several
inflammatory factors (like CXCL-1, iNOS, TNF-alpha and S100A8) as well as immune
cell marker genes (e.g. LFA-1, CD68, Ly6G) in the joints of KSRP-/- mice. Spleen
cells of KSRP-/- mice showed lower frequencies of myeloid cells. On cytokine
level IFN-gamma production was increased in spleen cells of KSRP-/- mice compared
to WT samples. These data surprisingly suggest that the absence of KSRP protects
against the induction of inflammatory arthritis.
PMID- 28511091
TI - Molecular cloning and characterization of DNGR-1 in rhesus macaques.
AB - DC, NK lectin group receptor-1 (DNGR-1), also known as C-type lectin domain
family 9 member A (CLEC9A), is a promising target for immunological therapeutics
and vaccination against tumors and viruses. However, little is known about its
property in rhesus macaques. In this study, we cloned rhesus macaque DNGR-1 cDNA,
and found that its coding region could encode a 241-amino acid polypeptide with
91.7% sequence identity and similar antigenicity to that of humans. Both free and
cell surface rhesus macaque DNGR-1 expressed in vitro could bind to
apoptotic/dead cells induced by serum deprivation or freeze-thaw, and to
pyroptotic cells stimulated with PMA and LPS. We also demonstrated that rhesus
macaque DNGR-1 mRNA was present in all the examined tissues, with the highest in
lymph nodes, spleen, blood, and thymus. The expression of DNGR-1 that is highly
similar to that of humans warranted the usefulness of rhesus macaques in testing
human therapeutics and vaccines targeting DNGR-1, especially those for HIV/AIDS.
PMID- 28511092
TI - Epigenetics and immunotherapy: The current state of play.
AB - Cancer cells employ a number of mechanisms to escape immunosurveillance and
facilitate tumour progression. The recent explosion of interest in immunotherapy,
especially immune checkpoint blockade, is a result of discoveries about the
fundamental ligand-receptor interactions that occur between immune and cancer
cells within the tumour microenvironment. Distinct ligands expressed by cancer
cells engage with cell surface receptors on immune cells, triggering inhibitory
pathways (such as PD-1/PD-L1) that render immune cells immunologically tolerant.
Importantly, recent studies on the role of epigenetics in immune evasion have
exposed a key role for epigenetic modulators in augmenting the tumour
microenvironment and restoring immune recognition and immunogenicity. Epigenetic
drugs such as DNA methyltransferase and histone deacetylase inhibitors can
reverse immune suppression via several mechanisms such as enhancing expression of
tumour-associated antigens, components of the antigen processing and presenting
machinery pathways, immune checkpoint inhibitors, chemokines, and other immune
related genes. These discoveries have established a highly promising basis for
studies using combined epigenetic and immunotherapeutic agents as anti-cancer
therapies. In this review, we discuss the exciting role of epigenetic
immunomodulation in tumour immune escape, emphasising its significance in priming
and sensitising the host immune system to immunotherapies through mechanisms such
as the activation of the viral defence pathway. With this background in mind, we
highlight the promise of combined epigenetic therapy and immunotherapy, focusing
on immune checkpoint blockade, to improve outcomes for patients with many
different cancer types.
PMID- 28511093
TI - Hypoxia-based strategies for regenerative dentistry-Views from the different
dental fields.
AB - The understanding of the cell biological processes underlying development and
regeneration of oral tissues leads to novel regenerative approaches. Over the
past years, knowledge on key roles of the hypoxia-based response has become more
profound. Based on these findings, novel regenerative approaches for dentistry
are emerging, which target cellular oxygen sensors. These approaches include
hypoxia pre-conditioning and pharmacologically simulated hypoxia. The increase in
studies on hypoxia and hypoxia-based strategies in regenerative dentistry
highlights the growing attention to hypoxia's role in regeneration and its
underlying biology, as well as its application in a therapeutic setting. In this
narrative review, we present the current knowledge on the role of hypoxia in oral
tissues and review the proposed hypoxia-based approaches in different fields of
dentistry, including endodontics, orthodontics, periodontics, and oral surgery.
PMID- 28511094
TI - Isolation and genetic analysis of pure cells from forensic biological mixtures:
The precision of a digital approach.
AB - Latest genotyping technologies allow to achieve a reliable genetic profile for
the offender identification even from extremely minute biological evidence. The
ultimate challenge occurs when genetic profiles need to be retrieved from a
mixture, which is composed of biological material from two or more individuals.
In this case, DNA profiling will often result in a complex genetic profile, which
is then subject matter for statistical analysis. In principle, when more
individuals contribute to a mixture with different biological fluids, their
single genetic profiles can be obtained by separating the distinct cell types
(e.g. epithelial cells, blood cells, sperm), prior to genotyping. Different
approaches have been investigated for this purpose, such as fluorescent-activated
cell sorting (FACS) or laser capture microdissection (LCM), but currently none of
these methods can guarantee the complete separation of different type of cells
present in a mixture. In other fields of application, such as oncology,
DEPArrayTM technology, an image-based, microfluidic digital sorter, has been
widely proven to enable the separation of pure cells, with single-cell precision.
This study investigates the applicability of DEPArrayTM technology to forensic
samples analysis, focusing on the resolution of the forensic mixture problem. For
the first time, we report here the development of an application-specific
DEPArrayTM workflow enabling the detection and recovery of pure homogeneous cell
pools from simulated blood/saliva and semen/saliva mixtures, providing full
genetic match with genetic profiles of corresponding donors. In addition, we
assess the performance of standard forensic methods for DNA quantitation and
genotyping on low-count, DEPArrayTM-isolated cells, showing that pure, almost
complete profiles can be obtained from as few as ten haploid cells. Finally, we
explore the applicability in real casework samples, demonstrating that the
described approach provides complete separation of cells with outstanding
precision. In all examined cases, DEPArrayTM technology proves to be a
groundbreaking technology for the resolution of forensic biological mixtures,
through the precise isolation of pure cells for an incontrovertible attribution
of the obtained genetic profiles.
PMID- 28511095
TI - Independent validation of DNA-based approaches for age prediction in blood.
AB - Numerous molecular biomarkers have been proposed as predictors of chronological
age. Among them, T-cell specific DNA rearrangement and DNA methylation markers
have been introduced as forensic age predictors in blood because of their high
prediction accuracy. These markers appear highly promising, but for better
application to forensic casework sample analysis the proposed markers and
genotyping methods must be tested further. In the current study, signal-joint T
cell receptor excision circles (sjTRECs) and DNA methylation markers located in
the ELOVL2, C1orf132, TRIM59, KLF14, and FHL2 genes were reanalyzed in 100 Korean
blood samples to test their associations with chronological age, using the same
analysis platform used in previous reports. Our study replicated the age
association test for sjTREC and DNA methylation markers in the 5 genes in an
independent validation set of 100 Koreans, and proved that the age predictive
performance of the previous models is relatively consistent across different
population groups. However, the extent of age association at certain CpG loci was
not identical in the Korean and Polish populations; therefore, several age
predictive models were retrained with the data obtained here. All of the 3 models
retrained with DNA methylation and/or sjTREC data have a CpG site each from the
ELOVL2 and FHL2 genes in common, and produced better prediction accuracy than
previously reported models. This is attributable to the fact that the retrained
model better fits the existing data and that the calculated prediction accuracy
could be higher when the training data and the test data are the same. However,
it is notable that the combination of different types of markers, i.e., sjTREC
and DNA methylation, improved prediction accuracy in the eldest group. Our study
demonstrates the usefulness of the proposed markers and the genotyping method in
an independent dataset, and suggests the possibility of combining different types
of DNA markers to improve prediction accuracy.
PMID- 28511096
TI - Improved amplification results following episodes of failure to amplify at the
Amelogenin Locus using PowerPlex(r) ESI 16 Fast System.
AB - In 2012 the Israel Police DNA Casework laboratory adopted the 16 STR PowerPlex(r)
ESI kit for routine use. The Promega Company updated this kit and developed the
PowerPlex(r) ESI 16 Fast System in which all autosomal primer pairs remained
identical to the original set, except at the amelogenin site. The master mix was
improved and optimized which allowed for direct, faster and more robust
amplification. Prior to implementing the PowerPlex(r) ESI 16 Fast System in our
lab, we conducted a preliminary assay where 213 casework samples were amplified
using the new kit. These samples had previously been extracted by one of two
extraction kits employed by our lab. (the PrepFiler ExpressTM and PrepFiler BTATM
Forensic DNA Extraction Kits). The amplification results from these samples were
compared to samples amplified using the original PowerPlex(r) ESI 16 kit.
Multiple incidents of failure to amplify at the amelogenin locus were noted using
the new system with the recommended protocol at a rate of 13% (28 of 213
samples). Experiments were performed to understand whether these amplification
failures could be a result of primer binding site mutations, extraction method
reagents and/or inhibitors. The conclusions reached following these experiments,
in conjunction with consultation with the manufacturer, led to the trial of a
modified amplification protocol where the suggested annealing temperature was
reduced by 2 degrees. To evaluate the efficiency of this altered protocol, a
comparison study was undertaken where 88 additional casework samples were chosen
and amplified using both the modified 58 degrees C and the recommended 60 degrees
C annealing temperatures. We concluded that the most effective method in our
laboratory for achieving a consistent and balanced amplification at the
amelogenin locus was to reduce the annealing temperature from the manufacturer's
recommended 60 degrees C to 58 degrees C. This modification resulted in a
reduction of the failure to amplify at the amelogenin locus from 13% (28/213) to
1.1% (1/88) without any observed changes to the autosomal STR amplification
results.
PMID- 28511097
TI - The relationship between social desirability bias and self-reports of health,
substance use, and social network factors among urban substance users in
Baltimore, Maryland.
AB - BACKGROUND: Social desirability response bias may lead to inaccurate self-reports
and erroneous study conclusions. The present study examined the relationship
between social desirability response bias and self-reports of mental health,
substance use, and social network factors among a community sample of inner-city
substance users. METHODS: The study was conducted in a sample of 591 opiate and
cocaine users in Baltimore, Maryland from 2009 to 2013. Modified items from the
Marlowe-Crowne Social Desirability Scale were included in the survey, which was
conducted face-to-face and using Audio Computer Self Administering Interview
(ACASI) methods. RESULTS: There were highly statistically significant differences
in levels of social desirability response bias by levels of depressive symptoms,
drug use stigma, physical health status, recent opiate and cocaine use, Alcohol
Use Disorders Identification Test (AUDIT) scores, and size of social networks.
There were no associations between health service utilization measures and social
desirability bias. In multiple logistic regression models, even after including
the Center for Epidemiologic Studies Depression Scale (CES-D) as a measure of
depressive symptomology, social desirability bias was associated with recent drug
use and drug user stigma. Social desirability bias was not associated with
enrollment in prior research studies. CONCLUSIONS: These findings suggest that
social desirability bias is associated with key health measures and that the
associations are not primarily due to depressive symptoms. Methods are needed to
reduce social desirability bias. Such methods may include the wording and
prefacing of questions, clearly defining the role of "study participant," and
assessing and addressing motivations for socially desirable responses.
PMID- 28511098
TI - E-cigarette liquids: Constancy of content across batches and accuracy of
labeling.
AB - AIMS: To assess whether bottles of refill liquids for e-cigarettes were filled
true to label, whether their content was constant across two production batches,
and whether they contained impurities. METHODS: In 2013, we purchased on the
Internet 18 models from 11 brands of e-liquids. We purchased a second sample of
the same models 4months later. We analyzed their content in nicotine, anabasine,
propylene glycol, glycerol, ethylene glycol and diethylene glycol, and tested
their pH. RESULTS: The median difference between the nicotine value on the labels
and the nicotine content in the bottles was 0.3mg/mL (range -5.4 to +3.5mg/mL,
i.e. -8% to +30%). For 82% of the samples, the actual nicotine content was within
10% of the value on the labels. All models contained glycerol (median 407mg/mL),
and all but three models contained propylene glycol (median 650mg/mL). For all
samples, levels of anabasine, ethylene glycol and diethylene glycol were below
our limits of detection. The pH of all the e-liquids was alkaline (median pH=9.1;
range 8.1 to 9.9). The measured content of two batches of the same model varied
by a median of 0% across batches for propylene glycol, 1% for glycerol, 0% for
pH, and 0.5% for nicotine (range -15% to +21%; 5th and 95th percentiles: -15% and
+10%). CONCLUSIONS: The nicotine content of these e-liquids matched the labels on
the bottles, and was relatively constant across production batches. The content
of propylene glycol and glycerol was also stable across batches, as was the pH.
PMID- 28511099
TI - The social exigencies of the gateway progression to the use of illicit drugs from
adolescence into adulthood.
AB - BACKGROUND: There is limited empirical integration between peer clustering theory
and the Gateway framework. The goal of the present study was to test the
hypothesis that friendship associations partly predict gateway escalations in the
use of drugs from adolescence to adulthood. METHOD: This longitudinal study
analyzed 3 waves of data from a community sample of 711 male and female
participants without a history of illicit drug use reporting drug use at age 17,
22, and 27. Substance use assessments including tobacco, alcohol, cannabis, onset
and abuse/dependence tendency of illicit drugs other than cannabis (i.e.,
cocaine, methamphetamine, and opiates), and friends' reported use of illicit
drugs. Structural equation modeling was used to test the hypothesized model.
RESULTS: Participants' cannabis use level at age 17 was positively associated
with perceived friends' drug use at age 22, which in turn predicted participants'
onset of illicit drug use between ages 22 and 27. Moreover, progression of
tobacco use throughout age 17 to 22 was associated with an increased onset of
illicit drug use between ages 22 and 27. Apart for an effect of cannabis use at
age 22 on abuse and dependence tendency to various drugs at age 28, results were
similar. CONCLUSIONS: During this period of development, the availability and
selection of drug-using friends contributes to the progression to potentially
more rewarding and damaging illicit drugs. These findings suggest the need to
attend to the peer ecology in prevention and support the common practice of using
abstaining peers in treatment for drug dependence.
PMID- 28511100
TI - Dahlia-shaped BiOClxI1-x structures prepared by a facile solid-state method:
Evidence and mechanism of improved photocatalytic degradation of rhodamine B dye.
AB - A rapid and cheap solid-state chemical process was employed to synthesize
BiOClxI1-x (x=1.0, 0.75, 0.5, 0.25, 0) solid solutions with dahlia-shaped
hierarchitectures. The dahlia-shaped BiOClxI1-x hierarchitectures were
effectively constructed by nanoplates with a thickness about 5-13nm. The band gap
structure of the solid solutions can be modulated by adjusting the composition
ratio of Cl and I, which has a significant effect on the photocatalytic activity
of the solid solutions. The dahlia-shaped BiOClxI1-x (x=0.75) solid solution
exhibits excellent adsorption and effective photocatalytic performances for
rhodamine B (RhB) under visible light irradiation, which degraded more than 98%
of RhB within 60min under the visible light irradiation, it is higher than the
reported bismuth oxyhalides materials. The trapping experiments confirmed that O2
and h+ played the major role in the photocatalytic process and the possible
photocatalytic reaction mechanism was illustrated.
PMID- 28511101
TI - Stable and self-healing superhydrophobic MnO2@fabrics: Applications in self
cleaning, oil/water separation and wear resistance.
AB - In this work, superhydrophobic fabrics were prepared through an in-situ growth
method for fabricating hierarchical flower-like MnO2 nanoparticles on cotton
fabric surface and subsequent STA modification, which exhibited multifunction for
self-healing, self-cleaning, oil/water separation and wear resistance. After air
plasma treatment, the self-healing MnO2@fabric could restore superhydrophobicity
by a short time heat treatment, and the water CA without obvious reduction after
8 cycles. Moreover, the MnO2@fabric could selectively filtrate oil from a mixture
of oil and water repeatedly, and demonstrated high efficiency for oil/water
separation capability and excellent self-cleaning property. Furthermore, the
MnO2@fabric composite possessed high mechanical strength and good wear
resistance, its wear rate could be reduced to 1.21*10-14m3 (Nm)-1. The
MnO2@fabric still maintained superhydrophobicity even was seriously damaged after
the friction test.
PMID- 28511102
TI - Highly effective antibacterial activity by the synergistic effect of three
dimensional ordered mesoporous carbon-lysozyme composite.
AB - Aiming at developing a safe and efficient alternative to traditional drinking
water disinfection, this work successfully synthesized a novel antibacterial
material with high surface area, ultra large pore size and tunable loading of
immobilized lysozyme. The immobilized enzymes exhibit high antibacterial efficacy
without forming carcinogenic disinfection byproducts. Critical immobilization
parameters were optimized to keep the activity of the immobilized enzyme at a
high level. The immobilization of lysozymes on 3DOm COOH could be confirmed by
the characterizations of transmission electron microscopy, X-ray diffraction and
Zeta-Potential. In addition, the structural stability of lysozymes on 3DOm COOH
were studied by Fourier transform infrared spectroscopy. The antibacterial
performance of 3DOm COOH-Lyz were specifically investigated based on the
disinfection efficacy of Staphylococcus aureus in water. The results revealed
that the immobilization capacity and relative activity of immobilized lysozyme
were 814mg/g carrier and 80%, respectively, under the optimal immobilization
conditions. And the antibacterial material with the initial mass ratio of
lysozyme and 3DOm COOH as 3:1 exhibited maximum bacteria removal efficiency
(98.1%) at pH 5. Moreover, the reusability test indicated that 3DOm COOH-Lyz has
certain operational stability, and remains 82% bacterial removal efficiency even
in the fifth cycle, which provides a promising application for safe and efficient
drinking water disinfection in small-scale and emergency water treatment.
PMID- 28511103
TI - The detection of 'virtual' objects using echoes by humans: Spectral cues.
AB - Some blind people use echoes to detect discrete, silent objects to support their
spatial orientation/navigation, independence, safety and wellbeing. The
acoustical features that people use for this are not well understood. Listening
to changes in spectral shape due to the presence of an object could be important
for object detection and avoidance, especially at short range, although it is
currently not known whether it is possible with echolocation-related sounds.
Bands of noise were convolved with recordings of binaural impulse responses of
objects in an anechoic chamber to create 'virtual objects', which were analysed
and played to sighted and blind listeners inexperienced in echolocation. The
sounds were also manipulated to remove cues unrelated to spectral shape. Most
listeners could accurately detect hard flat objects using changes in spectral
shape. The useful spectral changes for object detection occurred above
approximately 3 kHz, as with object localisation. However, energy in the sounds
below 3 kHz was required to exploit changes in spectral shape for object
detection, whereas energy below 3 kHz impaired object localisation. Further
recordings showed that the spectral changes were diminished by room
reverberation. While good high-frequency hearing is generally important for
echolocation, the optimal echo-generating stimulus will probably depend on the
task.
PMID- 28511104
TI - Lumbar extensor muscle force control is associated with disability in people with
chronic low back pain.
AB - BACKGROUND: The ability to control lumbar extensor force output is necessary for
daily activities. However, it is unknown whether this ability is impaired in
chronic low back pain patients. Similarly, it is unknown whether lumbar extensor
force control is related to the disability levels of chronic low back pain
patients. METHODS: Thirty-three chronic low back pain and 20 healthy people
performed lumbar extension force-matching task where they increased and decreased
their force output to match a variable target force within 20%-50% maximal
voluntary isometric contraction. Force control was quantified as the root-mean
square-error between participants' force output and target force across the
entire, during the increasing and decreasing portions of the force curve. Within-
and between-group differences in force-matching error and the relationship
between back pain group's force-matching results and their Oswestry Disability
Index scores were assessed using ANCOVA and linear regression respectively.
FINDINGS: Back pain group demonstrated more overall force-matching error (mean
difference=1.60 [0.78, 2.43], P<0.01) and more force-matching error while
increasing force output (mean difference=2.19 [1.01, 3.37], P<0.01) than control
group. The back pain group demonstrated more force-matching error while
increasing than decreasing force output (mean difference=1.74, P<0.001, 95%CI
[0.87, 2.61]). A unit increase in force-matching error while decreasing force
output is associated with a 47% increase in Oswestry score in back pain group
(R2=0.19, P=0.006). INTERPRETATION: Lumbar extensor muscle force control is
compromised in chronic low back pain patients. Force-matching error predicts
disability, confirming the validity of our force control protocol for chronic low
back pain patients.
PMID- 28511105
TI - Quadriceps rate of torque development and disability in individuals with anterior
cruciate ligament reconstruction.
AB - BACKGROUND: The purpose of this study was to determine associations between self
reported function (International Knee Documentation Committee Index), isometric
quadriceps strength and rate of torque development in individuals with a
unilateral anterior cruciate ligament reconstruction. METHODS: Forty-one
individuals [31% male, BMI mean 25 (SD 4) kg/m2, months post anterior cruciate
ligament reconstruction mean 49 (SD 40)] completed the self-reported function and
isometric quadriceps function testing. Rate of torque development was assessed at
0-100ms (early), 100-200ms (late) ms, and peak following the onset of
contraction. Associations were examined between rate of torque development,
strength, and self-reported function. Linear regression was used to determine the
unique amount of variance explained by the combination of rate of torque
development and strength. FINDINGS: Higher rate of torque development 100-200ms
is weakly associated with higher self-reported function in individuals with a
unilateral anterior cruciate ligament reconstruction (r=0.274, p=0.091); however,
rate of torque development 100-200ms does not predict a significant amount of
variance in self-reported function after accounting for strength (DeltaR2=0.003,
P=0.721). INTERPRETATION: Quadriceps strength has a greater influence on self
reported function compared to rate of torque development in individuals with an
anterior cruciate ligament reconstruction with time from surgery.
PMID- 28511106
TI - Mechanical properties and numerical simulation of Sulcata tortoise carapace.
AB - Carapace of Sulcata tortoise acts as a natural shield that protects the body from
natural predators. The carapace consists of four layers: keratin scutes, dorsal
cortex, cancellous interior and ventral cortex. This study aims to investigate
the load-bearing mechanisms of the carapace by characterizing the layers,
measuring their mechanical properties and relating them to the macroscopic
behavior under compression and bending loads. Test results indicate the influence
of layers' morphology, especially porosity and structural compositions, on the
macroscopic properties of the carapace. The bending samples are simulated using a
commercial finite element code as laminate composite structures with homogeneous
elastic layers. The models are shown to capture the load-displacement response of
the carapace in the elasticity regime under quasi-static loadings.
PMID- 28511107
TI - Frequent emergency department presentations among people who inject drugs: A
record linkage study.
AB - BACKGROUND: People who inject drugs (PWID) have been described as frequent users
of health services such as emergency departments (EDs), however few studies have
described demographic factors, patterns of substance use and previous health
service use associated with frequent use of EDs in this population. METHODS:
Using a combination of self-reported data from a cohort of PWID and
administrative ED data obtained through record linkage, we identified
longitudinal factors associated with the use of ED services. Bivariate and
multivariate analyses were conducted using negative binomial regression to
identify exposures associated with both cumulative ED presentations, and logistic
regression to identify exposures of frequent ED presentations (defined as three
or more annual presentations). RESULTS: Among 612 PWID, over half (58%) presented
to EDs at least once and over a third (36%) presented frequently between January
2008 and June 2013. Frequent and cumulative ED presentations were associated with
reporting the main drug of choice as cannabis (AOR:1.42, 95%CI:1.07-1.89 and
AIRR:2.96, 95%CI:1.44-6.07 respectively) or methamphetamine (AOR:1.62, 95%CI:1.17
2.2 and AIRR:2.42, 95%CI:1.08-5.46 respectively) compared to heroin, and past
month use of mental health (AOR:1.42, 95%CI:1.08-1.85 and AIRR:3.32, 95%CI:1.69
6.53 respectively) and outpatient services (AOR:1.47, 95%CI: 1.00-2.16 and
AIRR:0.95, 95%CI 1.52-10.28 respectively). CONCLUSION: PWID who are frequent
users of EDs are likely to have complex health and substance use-related needs.
EDs should actively refer people who present with cannabis and methamphetamine
dependence to harm reduction services. Harm reduction services should ensure
people referred from EDs are screened for co-occurring mental health conditions
and receive adequate support.
PMID- 28511108
TI - Wine yeasts identification by MALDI-TOF MS: Optimization of the preanalytical
steps and development of an extensible open-source platform for processing and
analysis of an in-house MS database.
AB - Saccharomyces cerevisiae is the most important yeast species for the production
of wine and other beverages. In addition, nowadays, researchers and winemakers
are aware of the influence of non-Saccharomyces in wine aroma complexity. Due to
the high microbial diversity associated to several agro-food processes, such as
winemaking, developing fast and accurate methods for microbial identification is
demanded. In this context, MALDI-TOF MS mass fingerprint provides reliable tool
for fast biotyping and classification of microorganisms. However, there is no
versatile and standardized method for fungi currently available. In this study,
an optimized sample preparation protocol was devised for the biotyping of yeasts
of oenological origin. Taking into account that commercially available reference
databases comprise almost exclusively clinical microorganisms, most of them
bacteria, in the present study a database of yeasts isolated from vineyards and
wineries was created, and its accuracy was tested using industrial and laboratory
yeast strains. In addition, the implementation of a program for MALDI-TOF MS
spectra analysis has been developed as an extensible open-source platform for
MALDI data processing and analysis with statistical techniques that has arisen
from our previous experience working with MALDI data. The software integrates two
R packages for raw MALDI data preprocessing: Continuous Wavelet Transform (CWT)
based algorithm and MassSpecWavelet. One of the advantages of the CWT is that it
can be directly applied to a raw spectrum, without prior baseline correction.
Mass fingerprints of 109 S. cerevisiae strains and 107 non-Saccharomyces isolates
were generated by MALDI-TOF MS upon optimized sample preparation and instrument
settings and analyzed for strain, species, and genus-level differentiation. As a
reference method, for S. cerevisiae differentiation at strain level, the analysis
of the polymorphism in the inter-delta region was chosen. The data revealed that
MALDI-TOF MS can be used for the rapid and accurate identification of S.
cerevisiae and non-Saccharomyces isolates at genus and species level. However, S.
cerevisiae differentiation at strain level was not successfully achieved, and the
differentiation among Metschnikowia species was also difficult.
PMID- 28511109
TI - Sensitive detection of viable Escherichia coli O157:H7 from foods using a
luciferase-reporter phage phiV10lux.
AB - Escherichia coli O157:H7, a major foodborne pathogen, is a major public health
concern associated with life-threatening diseases such as hemolytic uremic
syndrome. To alleviate this burden, a sensitive and rapid system is required to
detect this pathogen in various kinds of foods. Herein, we propose a phage-based
pathogen detection method to replace laborious and time-consuming conventional
methods. We engineered an E. coli O157:H7-specific phage phiV10 to rapidly and
sensitively detect this notorious pathogen. The luxCDABE operon was introduced
into the phiV10 genome and allowed the engineered phage phiV10lux to generate
bioluminescence proportional to the number of viable E. coli O157:H7 cells
without any substrate addition. The phage phiV10lux was able to detect at least
1CFU/ml of E. coli O157:H7 in a pure culture within 40min after 5h of pre
incubation. In artificially contaminated romaine lettuce, apple juice (pH3.51),
and ground beef, the reporter phage could detect approximately 10CFU/cm2,
13CFU/ml, and 17CFU/g of E. coli O157:H7, respectively. Taken together, the
constructed reporter phage phiV10lux could be applied as a powerful tool for
rapid and sensitive detection of live E. coli O157:H7 in foods.
PMID- 28511110
TI - Determination of regional relationships among Salmonella spp. isolated from
retail pork circulating in the Chiang Mai municipality area using a WGS data
approach.
AB - Salmonella is recognized as a significant zoonotic foodborne pathogen, and pork
products are involved in one-fifth of infections. Whole genome sequencing data of
Salmonella isolated from retail's pork circulating in the Chiang Mai Municipality
area between April 2013 and September 2014, were used to focus on genetic
diversity and proven in pig-human transmission based on Multilocus Sequence
Typing (MLST). Additionally, WGS data were used to investigate virulence genes,
to assess the hazard or pathogenic potential transferred into the food production
chain. In this study, all 32 Salmonella strains were classified into 11 Sequence
Types (STs). ST469 accounted for the majority (41%). The sequence types of two
other strains, 6% of the total, could not be identified. All tested strains
carried at least 15 virulence genes. The most frequent gene profile was "sfm-fim
sop-inv.-org-sip-spa-sif-fli-flg-hil-spr-ssa-sse-pag-bss" (47%). Salmonella
circulating in the study area demonstrated competence in biofilm production, host
cell adhesion, host cell invasion, and host cell survival. Based on the
phenotypic and genotypic findings, as well as pathogen source, it appears
possible that a common supply chain or common infection source might be presented
in the retail pork system in the study area. In addition, an epidemiological
comparison of the Salmonella genotypes from the current study with those from
other areas such as People's Republic of China (PR China) and the Lao People's
Democratic Republic (Lao PDR) was generated by Minimum spanning tree (MST).
Identical strains originating from humans, animals and food were found. The
findings indicate that contamination can be occured at all levels including pre
harvest, the farm-slaughterhouse-retail chain and consumers over different
geographical areas. Acquiring information about infection sources and
transmission routes will hopefully motivate all sectors to enforce strict
sanitation controls at all production stages including the consumer level.
PMID- 28511111
TI - Adaptive conditions and safety of the application of Penicillium frequentans as a
biocontrol agent on stone fruit.
AB - Penicillium frequentans (Pf909) reduces brown rot caused by Monilinia spp. in
stone fruit. The registration of a microbial biocontrol agent in Europe requires
information on the risks and safety of a biological product. This study focused
on the impact of the physical environment on Pf909 survival and growth, Pf909
mycotoxin production on fruit surface, and the Pf909 resistance to commercial
antifungal compounds used in animal and human medicine. The effect of temperature
(4 to 37 degrees C), water activity (0.999 to 0.900), pH (3 to 11), light
intensity (0, 90 and 180lm) and photoperiod (0/24, 12/12, 16/8, 24/0; light/dark)
on mycelial growth and sporulation of Pf909 were monitored for 10days in vitro on
culture medium. Antifungal activity of antifungal compounds on mycelial growth of
Pf909 was also measured by a quantitative micro spectrophotometric assay after
72h of incubation. The presence or absence of four non-volatile mycotoxins
(patulin, penicillic acid, ochratoxin A and citrinin) on nectarine surfaces
treated with Pf909 was determined by HPLC. Growth rate was significantly
influenced by water activity, temperature and light exposure conditions. Pf909
showed maximum growth and sporulation at 22 degrees C and 25 degrees C, in wet
conditions (0.999 water activity), with a pH5.6 to 9, and in darkness or a short
light photoperiod. Our results showed all antifungal compounds used reduced
significantly Pf909 mycelial growth at tested commercial doses. HPLC data
analysis showed that 7days after biofungicide (Pf909) application there were no
mycotoxin products on the surface of nectarine. Finally, no phylogenetic
relationship has been shown among Pf909 and other species of Penicillium that
produce mycotoxins. In conclusion, from an ecological point of view, Pf909 would
establish and survive actively over a broad range of climatic conditions. The
probability of risks to human and animal health is considered very low.
PMID- 28511112
TI - Real-time fluorescence assay of alkaline phosphatase in living cells using boron
doped graphene quantum dots as fluorophores.
AB - This work reports a convenient and real-time assay of alkaline phosphatase (ALP)
in living cells based on a fluorescence quench-recovery process at a
physiological pH using the boron-doped graphene quantum dots (BGQDs) as
fluorophore. The fluorescence of BGQDs is found to be effectively quenched by
Ce3+ ions because of the coordination of Ce3+ ions with the carboxyl group of
BGQDs. Upon addition of adenosine triphosphate (ATP) into the system, the
quenched fluorescence can be recovered by the ALP-positive expressed cells (such
as MCF-7 cells) due to the removal of Ce3+ ions from BGQDs surface by phosphate
ions, which are generated from ATP under catalytic hydrolysis of ALP that
expressed in cells. The extent of fluorescence signal recovery depends on the
level of ALP in cells, which establishes the basis of ALP assay in living cells.
This approach can also be used for specific discrimination of the ALP expression
levels in different type of cells and thus sensitive detection of those ALP
positive expressed cells (for example MCF-7 cells) at a very low abundance (10+/
5 cells mL-1). The advantages of this approach are that it has high sensitivity
because of the significant suppression of the background due to the Ce3+ ion
quenching the fluorescence of BGQDs, and has the ability of avoiding false
signals arising from the nonspecific adsorption of non-target proteins because it
operates via a fluorescence quench-recovery process. In addition, it can be
extended to other enzyme systems, such as ATP-related kinases.
PMID- 28511113
TI - Turn-on theranostic fluorescent nanoprobe by electrostatic self-assembly of
carbon dots with doxorubicin for targeted cancer cell imaging, in vivo
hyaluronidase analysis, and targeted drug delivery.
AB - This paper reports a turn-on theranostic fluorescent nanoprobe P-CDs/HA-Dox
obtained by electrostatic assembly of polyethylenimine (PEI)-modified carbon dots
(P-CDs) and Hyaluronic acid (HA)-conjugated doxorubicin (Dox) for hyaluronidase
(HAase) detection, self-targeted imaging and drug delivery. P-CDs/HA-Dox show
weak emission in a physiological environment. By utilizing the high affinity of
HA to CD44 receptors overexpressed on many cancer cells, P-CDs/HA-Dox are capable
of targeting and penetrating into cancer cells, where they are activated by
HAase. As a result, HA-Dox can be digested into small fragments, causing the
release of Dox and thereby restoring the fluorescence of P-CDs. The theranostic
fluorescent nanoprobe can effectively distinguish cancer cells from normal cells.
The as-prepared nanoprobe achieves a sensitive assay of HAase with a detection
limit of 0.65UmL-1. Furthermore, upon Dox release, the Dox could efficiently
induce apoptosis in HeLa cells, as confirmed by MTT assay. The design of such a
turn-on theranostic fluorescent probe provides a new strategy for self-targeted
and image-guided chemotherapy.
PMID- 28511114
TI - Bergapten prevents lipopolysaccharide-induced inflammation in RAW264.7 cells
through suppressing JAK/STAT activation and ROS production and increases the
survival rate of mice after LPS challenge.
AB - Bergapten (BG) is a cumarine-derivate compound in many medicinal plants. Here, in
vitro and in vivo experimental results indicated that BG possesses anti
inflammatory properties, Based on this, we further investigated the precise
molecular mechanisms of BG in LPS-stimulated inflammation response. Studies
revealed that BG inhibited LPS-stimulated productions of TNF-alpha, IL-1beta, IL
6, PGE2 and NO as well as the expression of iNOS and COX-2, and at the same time,
it increased LPS-induced release of IL-10 in a dose-dependent manner in RAW264.7
cells. Mechanistically, BG suppressed the activations of JAK/STAT, but not that
of MAPKs and NF-kappaB. In addition, BG, as an antioxidant, prevented the
accumulation of ROS, which further exerted its anti-inflammatory function. In
vivo researches revealed that BG decreased LPS-induced mortality in mice. In
conclusions, BG may be a potential candidate for inflammation therapy via
inhibiting JAK/STAT activation and ROS production in RAW264.7 cells.
PMID- 28511115
TI - Apoplastic ROS signaling in plant immunity.
AB - Reactive oxygen species (ROS) are widely produced in different cellular
compartments under both biotic and abiotic stress conditions. ROS play a central
role in plant signaling and regulate diverse cellular processes. Recent advances
are shedding new light on sophisticated mechanisms controlling ROS biogenesis and
signaling in plant immunity. In this review, we summarize our current
understanding of the regulation of apoplastic ROS production in response to
microbial molecular patterns and draw comparison with abscisic acid (ABA)-induced
apoplastic ROS. We also discuss how ROS act as signal molecules to regulate
cellular activities using stomatal movement as an example.
PMID- 28511116
TI - Functional RNA structures throughout the Hepatitis C Virus genome.
AB - The single-stranded Hepatitis C Virus (HCV) genome adopts a set of elaborate RNA
structures that are involved in every stage of the viral lifecycle. Recent
advances in chemical probing, sequencing, and structural biology have facilitated
analysis of RNA folding on a genome-wide scale, revealing novel structures and
networks of interactions. These studies have underscored the active role played
by RNA in every function of HCV and they open the door to new types of RNA
targeted therapeutics.
PMID- 28511117
TI - Conditioned medium from relapsing-remitting multiple sclerosis patients reduces
the expression and release of inflammatory cytokines induced by LPS-gingivalis in
THP-1 and MO3.13 cell lines.
AB - The present research was aimed at evaluating the effect of the conditioned medium
(CM) from human periodontal ligament stem cells (hPDLSCs) obtained from healthy
donors (hPDLSCs-CM) and from Relapsing-Remitting Multiple Sclerosis patients (RR
MS-CM) on inflammatory response induced by Porphyromonas gingivalis
lipopolysaccharide (LPS-G) in a monocytoid human cell line (THP-1) and human
oligodendrocyte cell line (MO3.13). Human periodontal ligament biopsies were
carried out from control donor patients and selected RR-MS donors. Sample tissues
were obtained from premolar teeth during root scaling and subsequently cultured.
The effect of hPDLSCs-CM and RR-MS-CM on cell viability in PMA differentiated THP
1 (as a model of microglia) was measured using a 3-[4,5-dimethylthiazol-2-yl]-2,5
diphenyltetrazolium bromide (MTT) assay. The same experiments were performed in
undifferentiated and differentiated MO3.13 cells used as models of progenitor
cells and oligodendrocytes, respectively. The expression of tumor necrosis factor
alpha (TNF)-alpha, interleukin (IL)-1beta and IL-6 was evaluated by Real-Time
Polymerase Chain Reaction (RT-PCR), and enzyme-linked immunosorbent assay
(ELISA). The expression level of the Toll-like receptor 4 (TLR-4), for which LPS
G is a ligand, was evaluated by Western blot analysis. The results were analyzed
by ANOVA using Graph Pad Prism software. LPS-G significantly increased TNFalpha,
IL-1beta and IL-6 mRNA expression and protein levels in the differentiated THP-1
cells and oligodendrocyte MO3.13 progenitor cells. Treatment with hPDLSCs-CM or
with RR-MS-CM significantly attenuated the LPS-induced expression and production
of these pro-inflammatory cytokines. The CM from both healthy donors and RR-MS
patients also reduced the LPS-G stimulated protein levels of TLR-4 in
differentiated THP-1 cells. On the whole our data add new evidence on the anti
inflammatory effects of these peculiar stem cells even when derived from RR-MS
patients and open novel perspectives in the therapeutic use of autologous
periodontal stem cells in neuroinflammatory/neurodegenerative diseases including
MS.
PMID- 28511118
TI - Simultaneous determination of selective serotonin reuptake inhibitors and their
main metabolites in human breast milk by liquid chromatography-electrospray mass
spectrometry.
AB - A bioanalytical method by high performance liquid chromatography coupled to
electrospray mass spectrometry (HPLC-ESI-MS), adapted from a previously published
method in plasma, was validated in breast milk for the simultaneous
quantification of all antidepressants belonging to the class of selective
serotonin reuptake inhibitors (citalopram, fluoxetine, fluvoxamine, paroxetine
and sertraline) and their major metabolites (desmethylcitalopram and
norfluoxetine). Milk samples (250MUl) first underwent protein precipitation
followed by solid-phase extraction on a reversed phase/cation exchange sorbent.
Analytes were thereafter separated on a XBridge C18 column (2.1mm*100mm; 3.5MUm)
using a mobile phase composed of ammonium acetate buffer (pH 8.1; 50mM) and
acetonitrile in gradient mode. Detection was performed by a single quadrupole
mass spectrometer running in selected ion monitoring in positive ionization mode.
Method validation covered a wide concentration range of 2-500ng/ml for
citalopram, desmethylcitalopram and paroxetine, 5-500ng/ml for sertraline, and 2
1000ng/ml for fluoxetine, norfluoxetine and fluvoxamine. Validation performances
such as trueness (90.3-111.6%), repeatability (0.8-9.3%) and intermediate
precision (0.9-9.5%) were in agreement with criteria from international
guidelines and matrix effects for the analyte/internal standard ratios ranged
from 92% to 110% (relative standard deviation <15%). Accuracy profiles (total
error of trueness and precision) were lying within the limits of +/-30% accepted
in bioanalysis. Finally, the method was successfully applied to patient samples
collected in a clinical pharmacokinetic study of nursing mothers taking an
antidepressant treatment.
PMID- 28511120
TI - Stokes flow patterns induced by a single cardiac cell.
AB - Stokes flow motions induced by a beating single cardiac cell (cardiomyocyte) are
obtained numerically using the method of fundamental solutions (MFS). A two
dimensional meshfree-Stokeslets computational framework is used to solve the
Stokes governing equations around an isolated cardiomyocyte. An approximate
beating kinematical model is derived and used to approximate the cell-length
shortening over a complete cardiac cycle. The induced flow patterns have been
found to be characterized by the presence of counter-rotating vortices at both
cell's edges. These vortical flow structures are clearly shown by rendering the
velocity streamlines. The static pressure contours are also calculated at
different time snapshots during both contraction and relaxation phases of the
beating motion. The pressure signal is calculated at a point in the neighborhood
of cell surface to capture the induced normal stress (traction) by the cell
morphological motions to the surrounding fluid medium. The presented results have
shown that, cells with a slightly different shortening/beating profile can induce
different flow field. This implies that, each cell is characterized by a unique
flow pattern "signature", which potentially can be correlated to the sub-cellular
excitation-contraction processes of cardiac cells.
PMID- 28511119
TI - Effects of breviscapine on amyloid beta 1-42 induced Alzheimer's disease mice: A
HPLC-QTOF-MS based plasma metabonomics study.
AB - Herba Erigerontis has long been used to cure apoplexy hemiplegia and precordial
pain in China. In addition, the bioactivities of its total flavonoids
breviscapine included inhibiting amyloid beta (Abeta) fibril formation,
antioxidation and metal chelating, which are beneficial to treat Alzheimer's
disease (AD). Hence, A HPLC-QTOF-MS based plasma metabonomics approach was
applied to investigate the neuroprotective effects of breviscapine on
intracerebroventricular injection of aggregated Abeta 1-42 induced AD mice for
the first time in the study. Ten potential biomarkers were screened out by
multivariate statistical analysis, eight of which were further identified as
indoleacrylic acid, C16 sphinganine, LPE (22:6), sulfolithocholic acid, LPC
(16:0), PA (22:1/0:0), taurodeoxycholic acid, and PC (0:0/18:0). According to
their metabolic pathways, it was supposed that breviscapine ameliorated the
learning and memory deficits of AD mice predominantly by regulating phospholipids
metabolism, elevating serotonin level and lowering cholesterols content in vivo.
PMID- 28511121
TI - Influence of different frequencies of axial cyclic loading on time-domain
vibration response of the lumbar spine: A finite element study.
AB - Very few studies have quantitatively analyzed influence of the loading frequency
on time-domain vibration response of the whole lumbar spine in the presence of a
physiologic compressive preload. In this study, a three-dimensional non-linear
finite element model of ligamentous L1-S1 segment was developed to predict time
domain dynamic response of the whole lumbar spine to axial cyclic loading with
different frequencies. A compressive follower preload of 400 N was applied to the
model to simulate the physiologic compressive load. Modal analysis was initially
performed to extract axial resonant frequency of the model under a 40 kg upper
body mass and the 400 N preload. The result showed that the axial resonant
frequency was 7.77 Hz. Subsequently, transient dynamic analyses were performed on
the model under a sinusoidal axial load of +/-40 N at frequencies of 3, 5, 7, 9,
11, 13 and 15 Hz with the 400 N preload and 40 kg mass. The computational results
(strains and stresses in the spinal components) were collected and plotted as a
function of time. These predicted results were found to be frequency-dependent
and consistent with the notion in engineering dynamics texts that the closer the
loading frequency approaches the resonant frequency, the larger the response is.
For example, the results for 5 Hz load compared to 3 Hz load showed a 68.6-111.5%
increase in peak-to-bottom variations of the predicted response parameters, and
the results for 13 Hz load compared to 11 Hz load showed a 26.4-37.8% decrease in
these variations.
PMID- 28511122
TI - Robotic assessment of neuromuscular characteristics using musculoskeletal models:
A pilot study.
AB - OBJECTIVE: Non-invasive neuromuscular characterization aims to provide greater
insight into the effectiveness of existing and emerging rehabilitation therapies
by quantifying neuromuscular characteristics relating to force production, muscle
viscoelasticity and voluntary neural activation. In this paper, we propose a
novel approach to evaluate neuromuscular characteristics, such as muscle fiber
stiffness and viscosity, by combining robotic and HD-sEMG measurements with
computational musculoskeletal modeling. This pilot study investigates the
efficacy of this approach on a healthy population and provides new insight on
potential limitations of conventional musculoskeletal models for this
application. METHODS: Subject-specific neuromuscular characteristics of the
biceps and triceps brachii were evaluated using robot-measured kinetics,
kinematics and EMG activity as inputs to a musculoskeletal model. RESULTS:
Repeatability experiments in five participants revealed large variability within
each subjects evaluated characteristics, with almost all experiencing variation
greater than 50% of full scale when repeating the same task. CONCLUSION: The use
of robotics and HD-sEMG, in conjunction with musculoskeletal modeling, to
quantify neuromuscular characteristics has been explored. Despite the ability to
predict joint kinematics with relatively high accuracy, parameter
characterization was inconsistent i.e. many parameter combinations gave rise to
minimal kinematic error. SIGNIFICANCE: The proposed technique is a novel approach
for in vivo neuromuscular characterization and is a step towards the realization
of objective in-home robot-assisted rehabilitation. Importantly, the results have
confirmed the technical (robot and HD-sEMG) feasibility while highlighting the
need to develop new musculoskeletal models and optimization techniques capable of
achieving consistent results across a range of dynamic tasks.
PMID- 28511123
TI - Dismissing the goals: A comparison of four goal-dismissive goal-free evaluations.
AB - This article provides a descriptive review of four goal-free evaluations (GFE).
GFE is an evaluation model where the evaluator conducts the evaluation without
knowledge of or reference to the evaluand's stated goals. The four non-randomly
sampled evaluation approaches represent articulated evaluation models in which
the evaluators ignore the goals of the intervention or project. Data collection
consisted of document analyses supplemented by semi-structured interviews with
the models' creators. The findings from these case studies include descriptions
of the evaluation models, the models' relationship to GFE, and eight
commonalities shared among the four models. The conclusion of this study is that
these GFEs are similar to other GFEs described in the literature in that they
examine outcomes as reported by the intervention's consumers, focus on collecting
qualitative data, and use their evaluations to supplement a larger goal-based
evaluation strategy.
PMID- 28511124
TI - Demonstration of short-term plasticity in the dorsolateral prefrontal cortex with
theta burst stimulation: A TMS-EEG study.
AB - OBJECTIVES: To examine the effects of intermittent TBS (iTBS) and continuous TBS
(cTBS) on cortical reactivity in the dorsolateral prefrontal cortex. METHODS: 10
healthy participants were stimulated with either iTBS, cTBS or sham at F3
electrode. Single- and paired-pulse TMS and concurrent electroencephalography
(EEG) were used to assess change in cortical reactivity and long-interval
intracortical inhibition (LICI) via TMS-evoked potentials (TEPs) and TMS-evoked
oscillations. RESULTS: Significant increases in N120 amplitudes (p<0.01) were
observed following iTBS over prefrontal cortex. Changes in TMS-evoked theta
oscillations and LICI of theta oscillations were also observed following iTBS
(increase) and cTBS (decrease). Change in LICI of theta oscillations correlated
with change in N120 amplitude following TBS (r=-0.670, p=0.001). CONCLUSIONS:
This study provides preliminary evidence that TBS produces direct changes in
cortical reactivity in the prefrontal cortex. Combining TBS with TMS-EEG may be a
useful approach to optimise stimulation paradigms prior to the conduct of
clinical trials. SIGNIFICANCE: TBS is able to modulate cortical reactivity and
cortical inhibition in the prefrontal cortex.
PMID- 28511126
TI - Endophenotyping in idiopathic adult onset cervical dystonia.
AB - OBJECTIVE: Idiopathic adult onset cervical dystonia (IAOCD) is considered to be a
partially penetrant autosomal dominant genetic condition. Dystonia may result
from genetic and environmental factors. In this view, part of the physiology
should be an endophenotype stemming from the genetic background. We assessed the
most discriminative test to separate patients with IAOCD and healthy controls for
further endophenotyping in non-affected 1st degree relatives. METHODS: We
included patients with IAOCD, their 1st degree relatives and healthy controls.
Tests performed: (1) Sensory temporal discrimination (visual, tactile, visuo
tactile), (2) Paired pulse paradigms using transcranial magnetic stimulation
(TMS), (3) Mental rotation paradigms. RESULTS: 45 patients with IAOCD, 23 healthy
controls and 14 non-affected 1st degree relatives were recruited. Visuo-tactile
temporal discrimination separated best between controls and patients as well as
between controls and 1st degree relatives. 36% of the latter had an abnormal
visuo-tactile temporal discrimination. No difference between patients and healthy
controls was found for the other paradigms. CONCLUSIONS: Visuo-tactile temporal
discrimination separates controls from patients with IAOCD and its 1st degree
relatives. 36% of the latter had abnormal visuo-tactile thresholds supporting the
role of visuo-tactile temporal discrimination as an endophenotype for IAOCD.
SIGNIFICANCE: Even though the study was of exploratory design, our findings
expand the understanding of endophenotypes in IAOCD.
PMID- 28511127
TI - Neurophysiology of synaptic functioning in multiple sclerosis.
AB - Multiple sclerosis (MS) is an inflammatory immune-mediate disorder of the central
nervous system (CNS), primarily affecting the myelin sheath and followed by
neurodegeneration. Synaptic alterations are emerging as critical determinants of
early neurodegeneration in MS. Inflammation-induced alterations of synaptic
transmission and plasticity have been investigated in vitro and also in human MS
using transcranial magnetic stimulation (TMS) techniques. Specific inflammatory
cytokines alter glutamatergic and GABAergic transmission, resulting in synaptic
hyperexcitability. In both experimental autoimmune encephalomyelitis (EAE) and
MS, excitotoxic damage and neurodegeneration are found even in the early phases
of disease, conversely inflammation persists in the progressive phases.
Inflammatory cytokines also affect synaptic plasticity, as both long-term
potentiation (LTP) and long-term depression (LTD) are altered in EAE and in MS
patients. In particular, inflammation profoundly subverts plasticity and
influence both clinical recovery after a relapse and disease course. Regulation
of neuronal activity by cytokines plays important roles in the neuro-immune
crosstalk involved in inflammation-associated excitotoxic neuronal damage, and in
the chance of developing compensatory plasticity. Innate and adaptive immunity
interact with the CNS in MS, in line with the concept that cytokines and
chemokines, in concert with neurotransmitters and neuropeptides, represent a
major communication system in the CNS.
PMID- 28511128
TI - Improving the repeatability of Motor Unit Number Index (MUNIX) by introducing
additional epochs at low contraction levels.
AB - OBJECTIVE: To evaluate the repeatability of (Motor Unit Number Index) MUNIX under
repeatability conditions, specify the origin of variations and provide strategies
for quality control. METHODS: MUNIX calculations were performed on the bicep
brachii muscles of eight healthy subjects. Negative effect of suboptimal
electrode positions on MUNIX accuracy was eliminated by employing the high
density surface electromyography technique. MUNIX procedures that utilized a
variety of surface interferential pattern (SIP) epoch recruitment strategies
(including the original MUNIX procedure, two proposed improvement strategies and
their combinations) were described. For each MUNIX procedure, ten thousands of
different SIP pools were constructed by randomly recruiting necessary SIP epochs
from a large SIP epoch pool (3 datasets, 9 independent electromyography
recordings at different contraction levels per dataset and 10 SIP epochs per
recording) and implemented for MUNIX calculation. The repeatability of each MUNIX
procedure was assessed by summarizing the resulting MUNIX distribution and
compared to investigate the effect of SIP epoch selection strategy on
repeatability performance. RESULTS: SIP epochs selected at lower contraction
levels have a stronger influence on the repeatability of MUNIX than those
selected at higher contraction levels. MUNIX under repeatability conditions
follows a normal distribution and the standard deviation can be significantly
reduced by introducing more epochs near the MUNIX definition line. CONCLUSIONS:
The MUNIX technique shows an inherent variation attributable to SIP epochs at low
contraction levels. It is recommended that more epochs should be sampled at these
low contraction levels to improve the repeatability. SIGNIFICANCE: The present
study thoroughly documented the inherent variation of MUNIX and the causes, and
offered practical solutions to improve the repeatability of MUNIX.
PMID- 28511129
TI - Neurophysiological and clinical outcomes in chemotherapy-induced neuropathy in
cancer.
AB - Chemotherapy induced peripheral neuropathy (CIPN) is a significant toxicity of
cancer treatment, with the potential to affect long-term function and quality of
life in cancer survivors. There remains a lack of consensus around optimal
assessment techniques. While current approaches to CIPN assessment are focused on
clinical grading scales, it is becoming increasingly evident that a more
comprehensive multimodal assessment package is necessary to accurately
characterise the impact of CIPN as well as gauge the utility of neuroprotective
mechanisms. Neurophysiological techniques provide objective biomarkers and may
enable early detection of toxicity while patient reported outcomes are necessary
to determine the significance of symptoms to individual patients. In addition to
providing an objective assessment, clinical neurophysiological techniques provide
important insights into the contributory pathophysiological mechanisms of CIPN
with different chemotherapy agents. There is a paucity of implementation of these
techniques in the clinical trial setting. The present Review aims to facilitate
the use of neurophysiological studies as part of comprehensive assessment
packages for the monitoring of CIPN by summarising current understanding of
neurophysiological changes that underlie the development of neuropathy, clinical
presentations and patient reported outcomes as well as advantages and limitations
of current techniques for the neurophysiological assessment of CIPN.
PMID- 28511125
TI - The many facets of motor learning and their relevance for Parkinson's disease.
AB - The final goal of motor learning, a complex process that includes both implicit
and explicit (or declarative) components, is the optimization and automatization
of motor skills. Motor learning involves different neural networks and
neurotransmitters systems depending on the type of task and on the stage of
learning. After the first phase of acquisition, a motor skill goes through
consolidation (i.e., becoming resistant to interference) and retention, processes
in which sleep and long-term potentiation seem to play important roles. The
studies of motor learning in Parkinson's disease have yielded controversial
results that likely stem from the use of different experimental paradigms. When a
task's characteristics, instructions, context, learning phase and type of
measures are taken into consideration, it is apparent that, in general, only
learning that relies on attentional resources and cognitive strategies is
affected by PD, in agreement with the finding of a fronto-striatal deficit in
this disease. Levodopa administration does not seem to reverse the learning
deficits in PD, while deep brain stimulation of either globus pallidus or
subthalamic nucleus appears to be beneficial. Finally and most importantly,
patients with PD often show a decrease in retention of newly learned skill, a
problem that is present even in the early stages of the disease. A thorough
dissection and understanding of the processes involved in motor learning is
warranted to provide solid bases for effective medical, surgical and
rehabilitative approaches in PD.
PMID- 28511130
TI - Design, synthesis and biological evaluation of uncharged catechol derivatives as
selective inhibitors of PTP1B.
AB - Protein tyrosine phosphatases 1B (PTP1B) is a promising and validated therapeutic
target to effectively treat T2DM and obesity. However, the development of charged
PTP1B inhibitors was restricted due to their low cell permeability and poor
bioavailability. Based on active natural products, two series of uncharged
catechol derivatives were identified as PTP1B inhibitors by targeting a secondary
aryl phosphate-binding site as well as the catalytic site. The most potent
inhibitor 22 showed an IC50 of 0.487 MUM against PTP1B and strong selectivity (27
fold) over TCPTP. Kinetic studies were also performed that 22 act as a
competitive PTP1B inhibitor. The treatment of C2C12 myotubes with 22 markedly
increased the phosphorylation levels of IRbeta, Akt and IRS1 phosphorylation. The
similarity of its action profiling with that produced by insulin suggested its
potential as a new non-insulin-dependent drug candidate.
PMID- 28511131
TI - Genetic diversity and phylogenetic analysis of the ORF5 gene of PRRSV from
central China.
AB - To more fully understand the genetic diversity and molecular epidemiology of
prevailing porcine reproductive and respiratory syndrome virus (PRRSV) in Henan
province of China, 112 full-length ORF5 gene sequences, originating from Henan
province between 2006 and 2015, were subjected to sequence variation and
phylogenetic analysis. Phylogenetic analysis revealed that all Henan isolates
belonged to the Type 2 genotype and could be further divided into three
subgroups. Subgroup 1 and 2 viruses predominated in Henan and subgroup 2 overtook
subgroup 1 as the most prevalent PRRSV between 2006 and 2015. Highly pathogenic
PRRSV (HP-PRRSV) isolates predominated in Henan and eight RespPRRSV MLV vaccine
like isolates were observed in subgroup 3. Sequence variation analysis revealed
that the ORF5 genes of all Henan isolates shared >83.3% nucleotide and >80.1%
amino acid sequence identity with each other. Primary neutralizing epitope (PNE)
analysis revealed that, relative to the attenuated RespPRRSV MLV vaccine isolate,
all but one of the subgroup 1 Henan isolates had mutations at amino acid 39
within the key PNE of GP5. Analysis of the immunoreceptor tyrosine-based
inhibitory motif (ITIM) in GP5 revealed that all but two of the Henan isolates
had a highly conserved sequence between amino acids 77 and 82 positions of GP5. N
linked glycosylation site (NGS) analysis revealed a novel potential NGS at GP5
amino acid position 59 in two of the subgroup 2 Henan isolates. Another novel GP5
amino acid mutation (44N->44D) was found in a single subgroup 1 Henan isolate
(HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV
infectivity.
PMID- 28511132
TI - Activity and in vivo dynamics of Bacillus subtilis DisA are affected by RadA/Sms
and by Holliday junction-processing proteins.
AB - Bacillus subtilis c-di-AMP synthase DisA and RecA-related RadA/Sms are involved
in the repair of DNA damage in exponentially growing cells. We provide genetic
evidence that DisA or RadA/Sms is epistatic to the branch migration translocase
(BMT) RecG and the Holliday junction (HJ) resolvase RecU in response to DNA
damage. We provide genetic evidence damage. Functional DisA-YFP formed dynamic
foci in exponentially growing cells, which moved through the nucleoids at a speed
compatible with a DNA-scanning mode. DisA formed more static structures in the
absence of RecU or RecG than in wild type cells, while dynamic foci were still
observed in cells lacking the BMT RuvAB. Purified DisA synthesizes c-di-AMP, but
interaction with RadA/Sms or with HJ DNA decreases DisA-mediated c-di-AMP
synthesis. RadA/Sms-YFP also formed dynamic foci in growing cells, but the foci
moved throughout the cells rather than just on the nucleoids, and co-localized
rarely with DisA-YFP foci, suggesting that RadA/Sms and DisA interact only
transiently in unperturbed conditions. Our data suggest a model in which DisA
moving along dsDNA indicates absence of DNA damage/replication stress via normal
c-di-AMP levels, while interaction with HJ DNA/halted forks leads to reduced c-di
AMP levels and an ensuing block in cell proliferation. RadA/Sms may be involved
in modulating DisA activities.
PMID- 28511133
TI - Phorate induced oxidative stress, DNA damage and differential expression of p53,
apaf-1 and cat genes in fish, Channa punctatus (Bloch, 1793).
AB - The present study was conducted to assess the in-vivo activities of certain
molecular biomarkers under the impact of phorate exposure. Fish, Channa punctatus
(35 +/- 3.0 g; 14.5 +/- 1.0 cm; Actinopterygii) were subjected to semi-static
conditions having 5% (0.0375 mg/L for T1 group) and 10% of 96 h-LC50 (0.075 mg/L
for T2 group) of phorate exposure for 15 and 30 d. The oxidative stress was
assessed in terms of superoxide dismutase (SOD) and catalase (CAT) activities.
DNA damage was measured as induction of micronuclei (MN) and consequent
differential expression of apoptotic genes-tumor suppressor (p53), apoptotic
peptidase activating factor-1 (apaf-1) and catalase (cat) in liver and kidney,
two major sites of biotransformation in fish, were quantified. Our findings
reveal significant (p < 0.001) augmentations in SOD and CAT activities of liver
and kidney tissues. MN frequency in erythrocytes of fish also increases
significantly (p < 0.05) in a dose- and time-dependent manner. The mRNA level of
p53 increased significantly (p < 0.05) in liver at 10% of 96 h-LC50 of phorate
exposure after 30 d suggesting generation of stress due to accumulation of
reactive oxygen species (ROS). Eventually, these findings decipher the dual role
of ROS in generating genotoxicity as is evident by micronuclei induction and
differential regulation of p53, apaf-1 and cat genes during the phorate induced
DNA damage and apoptosis in test fish. The experimental inferences drawn on the
basis of activities of aforesaid biomarkers shall be helpful in elucidating the
possible causes of apoptosis under stressful conditions. Further, this study
finds ample application in biomonitoring of phorate polluted aquatic ecosystem.
PMID- 28511134
TI - Cadmium toxicokinetics in the freshwater turtle, Chinemys reevesii.
AB - This study was designed to investigate the toxicokinetics of Cadmium (Cd) in
Chinemys reevesii. The animals were exposed to 15 mg/kg Cd chloride by
intraperitoneal injection, and the Cd absorption, distribution, and excretion in
different organs were determined. The results showed that Cd absorption reached
its peak in the blood at 3 h after treatment. The accumulation of Cd was the
highest in the liver and the second highest in the pancreas. All other tissues
also accumulated Cd, such as spleen, kidney, intestine, lung, stomach, heart,
brain, muscle. A small amount of Cd was found in the faeces. The urine and bile
had low concentrations of Cd. In conclusion, absorbance of Cd reaches its peak at
3 h in blood. The liver and pancreas are the major organs of Cd accumulation, and
the major excretion route of Cd is through feaces.
PMID- 28511135
TI - Solubility of organic compounds in octanol: Improved predictions based on the
geometrical fragment approach.
AB - Two new models are introduced to predict the solubility of chemicals in octanol
(Soct), taking advantage of the extensive character of log(Soct) through a
decomposition of molecules into so-called geometrical fragments (GF). They are
extensively validated and their compliance with regulatory requirements is
demonstrated. The first model requires just a molecular formula as input. Despite
an extreme simplicity, it performs as well as an advanced random forest model
involving 86 descriptors, with a root mean square error (RMSE) of 0.64 log units
for an external test set of 100 molecules. For the second one, which requires the
melting point Tm as input, introducing GF descriptors reduces the RMSE from about
0.7 to <0.5 log units, a performance that could previously be obtained only
through the use of Abraham descriptors. A script is provided for easy application
of the models, taking into account the limits of their applicability domains.
PMID- 28511136
TI - Fate of pharmaceuticals in soil after application of STPs products: Influence of
physicochemical properties and modelling approach.
AB - Depurated effluents can be employed as reclaimed water for irrigation in regions
with low precipitations, while nutrients-rich biosolids are usually applied as
fertilizer for agricultural purposes. However, both practices may result in the
accumulation of micropollutants in the soil compartment, the contamination of
groundwater, and/or their biotransfer to different living organisms until they
finally may reach human receptors. The fate and transport of seven pharmaceutical
and personal care products (PPCPs) with different physicochemical properties was
analysed for these scenarios employing two different models: the buckets model
and the HYDRUS-1D software package. The results indicated that these compounds
have a low potential to contaminate groundwater in the type of soil under study
(silty loam), although triclosan tended to accumulate in the top layers of the
soil. Similar conclusions were reached through both models, although they
predicted different solute plant uptake and accumulation patterns of the
evaluated compounds. Therefore, the buckets model can be considered as an
adequate option to perform a screening level assessment of these compounds.
However, HYDRUS-1D could provide more information on the fate of pharmaceuticals
in soil, thus contributing to reduce the uncertainty already associated to PPCPs.
Additionally, the significant difference of the Hazard Index (HI) obtained from a
human health risk assessment performed using the estimated soil concentrations
from both models also contributed to recommend the use of a model that considers
all the relevant mechanisms of mass transfer to reduce overestimation of risk.
PMID- 28511137
TI - Effects of ibuprofen, diclofenac and paracetamol on hatch and motor behavior in
developing zebrafish (Danio rerio).
AB - Non-steroidal anti-inflammatory drugs (NSAIDs) which are widely used as pain
relief medicines are causing increasing environmental concern due to their
incomplete removal in wastewater treatment plant and potential toxicity on
endocrine, kidney and reproduction in teleost fish. This study focused on the
effects of widely used ibuprofen, diclofenac and paracetamol on the hatch and
motor ability of early-stage zebrafish, by exposing embryos to the target
chemicals at 5, 50 and 500 MUg/L starting from 6 h postfertilization (hpf). A
significant reduction in hatch rate at 55 hpf was caused by both ibuprofen (-63%)
and diclofenac (-58%) at 500 MUg/L. Exposure to high concentration of ibuprofen
significantly decreased the spontaneous movement by 25%, and reduced the free
swimming distance, duration and speed under dark condition by 41%, 29% and 30%,
respectively. High concentration of diclofenac also caused 23% decrease in
spontaneous movement, and reduced the swimming distance as well as active
duration by 17% and 13% under light stimulation. In comparison, the exposure to
paracetamol did not cause any notable effect. Among neuron related genes tested,
the expression of neurog1 was down-regulated from ibuprofen and diclofenac
exposure by 19% and 26%, while the expression of neurod1 was up-regulated only by
ibuprofen (31%). These findings indicated that ibuprofen and diclofenac
significantly affected embryo locomotivity and were potentially neurotoxic, thus
posing threats to zebrafish development.
PMID- 28511138
TI - Neurodevelopment for the first three years following prenatal mobile phone use,
radio frequency radiation and lead exposure.
AB - BACKGROUND: Studies examining prenatal exposure to mobile phone use and its
effect on child neurodevelopment show different results, according to child's
developmental stages. OBJECTIVES: To examine neurodevelopment in children up to
36 months of age, following prenatal mobile phone use and radiofrequency
radiation (RFR) exposure, in relation to prenatal lead exposure. METHODS: We
analyzed 1198 mother-child pairs from a prospective cohort study (the Mothers and
Children's Environmental Health Study). Questionnaires were provided to pregnant
women at <=20 weeks of gestation to assess mobile phone call frequency and
duration. A personal exposure meter (PEM) was used to measure RFR exposure for
24h in 210 pregnant women. Maternal blood lead level (BLL) was measured during
pregnancy. Child neurodevelopment was assessed using the Korean version of the
Bayley Scales of Infant Development-Revised at 6, 12, 24, and 36 months of age.
Logistic regression analysis applied to groups classified by trajectory analysis
showing neurodevelopmental patterns over time. RESULTS: The psychomotor
development index (PDI) and the mental development index (MDI) at 6, 12, 24, and
36 months of age were not significantly associated with maternal mobile phone use
during pregnancy. However, among children exposed to high maternal BLL in utero,
there was a significantly increased risk of having a low PDI up to 36 months of
age, in relation to an increasing average calling time (p-trend=0.008). There was
also a risk of having decreasing MDI up to 36 months of age, in relation to an
increasing average calling time or frequency during pregnancy (p-trend=0.05 and
0.007 for time and frequency, respectively). There was no significant association
between child neurodevelopment and prenatal RFR exposure measured by PEM in all
subjects or in groups stratified by maternal BLL during pregnancy. CONCLUSIONS:
We found no association between prenatal exposure to RFR and child
neurodevelopment during the first three years of life; however, a potential
combined effect of prenatal exposure to lead and mobile phone use was suggested.
PMID- 28511139
TI - A successful transition to sulfonylurea treatment in male infant with neonatal
diabetes caused by the novel abcc8 gene mutation and three years follow-up.
AB - Neonatal diabetes mellitus is a rare monogenic disease with incidence of 1/90,000
newborns. A case of two months aged male infant with life threatening diabetic
ketoacidosis is presented with novel ABCC8 gene mutation (p.F577L), successful
transition from insulin to sulfonylurea and follow-up of three years.
PMID- 28511140
TI - Different impacts of acylated and non-acylated long-acting insulin analogs on
neural functions in vitro and in vivo.
AB - AIMS: Centrally administered insulin improves cognitive functions in patients
with Alzheimer's disease; however, it remains unknown whether long-acting insulin
analogs exert more pronounced effects than insulin. In the present study, we
directly compared the effects of insulin and its analogs on neural functions in
vitro and in vivo. METHODS: Cultured rat cerebral cortical neurons were treated
with insulin, insulin glargine U100 (Gla), insulin detemir (Det), or insulin
degludec (Deg). Moreover, these drugs were intracerebroventricularly administered
to mice. Their efficacies were evaluated by biochemical and behavioral analyses.
RESULTS: In cultured neurons, insulin, Gla, and Det increased phosphorylation of
Akt and enhanced gene expression of brain-derived neurotrophic factor to a
similar extent, although Deg was less effective. The effects of Det and Deg, but
not insulin and Gla were suppressed by addition of albumin. When the drug was
centrally administered, the increasing effects of insulin on the Akt
phosphorylation were comparable to those of Gla but greater than those of Det in
hippocampus and cerebral cortex of diabetic db/db and non-diabetic db/m+ mice.
Moreover, insulin and Gla enhanced memory functions in Y-maze test and suppressed
depression-like behavior in forced swim test in normal mice to a similar extent,
and these effects were more potent than those of Det. CONCLUSIONS: Insulin and
Gla have greater impacts on central nervous system than insulin analogs with high
albumin sensitivity, such as Det and Deg. These pharmacological profiles should
be taken into account for developing an insulin-based therapy to treat
Alzheimer's disease.
PMID- 28511141
TI - The co-occurrence of depressive symptoms and cognitive impairment and its
relationship with self-care behaviors among community dwelling older adults with
diabetes.
AB - AIMS: The aims of the present study were to investigate the co-occurrence of
depressive symptoms and cognitive impairment in community dwelling older adults
with diabetes and its relationship with specific diabetes self-care behaviors.
METHODS: We analyzed data from two national samples of older adults (65years or
older) with self-reported physician-diagnosed diabetes (N=1034), who participated
in the 2005 or 2009 National Health Interview Survey in Taiwan. The Mini-Mental
State Examination was used to assess cognitive function. The Center for
Epidemiologic Studies Depression Scale was used to assess depressive symptoms.
The study assessed self-care behaviors including medication adherence, exercise,
healthy diet, and self-monitoring of blood glucose. RESULTS: In this study, 8.8%
of participants with diabetes had both depressive symptoms and cognitive
impairment. After adjusting for other factors, participants with both cognitive
impairment and depressive symptoms were less likely to exercise (Prevalence
Ratios (PR)=0.66; 95% Confidence Intervals (CI)=[0.47-0.91]; P-value=0.011), and
have a healthy diet (PR=0.82; 95%CI=[0.70-0.96]; P-value=0.012). CONCLUSIONS: Our
results illustrate the high prevalence of combined depressive symptoms and
cognitive impairment and that this combination is associated with worse self-care
behaviors in older adults with diabetes. These findings highlight the difficulty
that some older adults with diabetes may have in maintaining self-care behaviors
in the presence of depressed mood and cognitive impairment, particularly in the
areas of diet and exercise. The results emphasize the importance of providing
more support for these aspects of self-care to such older adults.
PMID- 28511143
TI - DNA-assisted upconversion nanoplatform for imaging-guided synergistic therapy and
laser-switchable drug detoxification.
AB - The side effects of chemotherapy bring significant physical and psychological
suffering to patients. To solve this urgent medical problem, Yb3+ and Er3+ co
doped NaLuF4 upconversion nanoparticles (UCNPs) were constructed for upconversion
luminescence (UCL)-labeled diagnosis under 980 nm laser irradiation. The UCNPs
were then modified layer by layer with polypyrrole and a special programming DNA
segment as photothermal conversion agents and controllable drug carriers,
respectively. The nanoplatform was successfully used for imaging-guided
synergistic therapy (photothermal therapy and chemotherapy) at a safe power
density (300 mW cm-2), and DNA-assisted detoxification at lower temperature in
cancer cells when the laser off. The synergistic therapy of the nanoplatform
achieved a higher therapeutic index (~85%) than chemotherapy only (~44%) and
photothermal therapy only (~25%) in vitro. In vivo experiments also suggested
that the nanoplatform had a higher therapeutic effect and lower side effects. The
toxicity study was also evaluated, indicating the nanoplatform is low toxic to
living system. This multifunctional upconversion nanoplatform provided an
innovative method for imaging-guided photothermal-chemotherapy and laser
switchable drug detoxification.
PMID- 28511142
TI - Tailoring nanostructured lipid carriers for the delivery of protein antigens:
Physicochemical properties versus immunogenicity studies.
AB - New vaccine formulations are still highly anticipated in the near-future to face
incoming health challenges, such as emergence or reemergence of severe infectious
diseases, immunosenescence associated with elderly or the spread of pathogens
resistant to antibiotics. In particular, new nanoparticle-based adjuvants are
promising for sub-unit vaccines in order to elicit potent and long lasting immune
responses with a better control on their safety. In this context, an innovative
delivery system of protein antigens has been designed based on the chemical
grafting of the antigen onto the shell of Nanostructured Lipid Carriers (NLC). By
using the well-known ovalbumin (OVA) as model of protein antigen, we have
compared the immunogenicity properties in mice of different formulations of NLC
grafted with OVA, by studying the influence of two main parameters: the size (80
nm versus 120 nm) and the surface charge (anionic versus cationic). We have shown
that all mice immunized with OVA delivered through NLC produced much higher
antibody titers for all tested formulations as compared to that immunized with
OVA or OVA formulated in Complete Freund Adjuvant (CFA, positive control). More
interestingly, the 80 nm anionic lipid particles were the most efficient antigen
carrier for eliciting higher humoral immune response, as well as cellular immune
response characterized by a strong secretion of gamma interferon (IFN-gamma).
These results associated with the demonstrated non-immunogenicity of the NLC
carrier by itself open new avenues for the design of smart sub-unit vaccines
containing properly engineered lipid nanoparticles which could stimulate or
orient the immune system in a specific way.
PMID- 28511144
TI - Development of a prognostic scale for severely hemiplegic stroke patients in a
rehabilitation hospital.
AB - OBJECTIVES: For patients with severe hemiplegia in a rehabilitation hospital,
early prediction of the functional prognosis and outcomes is challenging. The
purpose of this study was to create and verify a prognostic scale in severely
hemiplegic stroke patients and allowing for prediction of (1) the ability to walk
at the time of hospital discharge, (2) the ability to carry out activities of
daily living (ADL), and (3) feasibility of home discharge. PATIENTS AND METHODS:
The study was conducted on 80 severely hemiplegic stroke patients. A prognostic
scale was created as an analysis method using the following items: mini-mental
state examination (MMSE) at the time of admission, modified NIH stroke scale (m
NIHSS); trunk control test (TCT); and the ratio of the knee extensor strength on
the non-paralyzed side to the body weight (KES/BW-US). We verified the
reliability and validity of this scale. RESULTS: We established a prognostic
scale using the MMSE, m-NIHSS, TCT, and KES/BW-US. A score of 56.8 or higher on
the prognostic scale suggested that the patient would be able to walk and that
assistance with ADL would be unnecessary at the time of hospital discharge. In
addition, a score of 41.3 points indicated that the patient's return home was
feasible. The reliability and the results were in good agreement. These findings
showed that the ability or inability to walk was predictable in 85%, the need of
assistance with ADL in 82.5%, and the feasibility of home return in 76.3% of
cases. CONCLUSION: At the time of admission, four evaluation items permitted the
prediction of three outcomes at time of discharge. Our formula predicts three
outcomes with an accuracy of more than 76%.
PMID- 28511145
TI - Plasma membrane repair: the adaptable cell life-insurance.
AB - The plasma membrane is the most basic element necessary for the cell to exist and
be distinguishable from its environment. Regulated mechanisms allow tightly
controlled communication between intacellular and extracellular medium allowing
the maintenance of a specific biochemical environment, optimized for cellular
functions. The anarchic and uncontrolled opening of a hole in the PM induces a
change in the concentration of ions and oxidizing agents perturbing homeostasis.
Fortunately, the cell possesses mechanisms that are capable of reacting to sudden
extracellular medium entry and to block the leakage locally. Here we summarize
the known mechanisms of membrane repair and how the size of the wound and the
resulting calcium entry activates preferentially one or another mechanism adapted
to the magnitude of the injury.
PMID- 28511146
TI - Real world prospective experience of axitinib in metastatic renal cell carcinoma
in a large comprehensive cancer centre.
AB - BACKGROUND: Axitinib has shown activity in metastatic renal cell carcinoma (mRCC)
in a large phase III clinical trial and was approved in patients who failed first
line therapy. This drug has been available in France since November 2012. The
objective is to report efficacy and safety of axitinib in mRCC outside of
clinical trials. METHODS: A prospective evaluation of mRCC patients treated by
axitinib in second or further next-line therapy at Gustave Roussy was conducted
from 2012 to 2015. Objective response rate (ORR), progression-free survival
(PFS), time to treatment failure (TTF), overall survival (OS) and toxicities were
analysed. The correlation between clinical markers and ORR, PFS, TTF and OS were
explored. RESULTS: One-hundred and sixty patients with mRCC, received axitinib in
second (40%) or further next-line therapy (60%). International Metastatic Renal
Cell Carcinoma Database Consortium (IMDC) risk group classification was good,
intermediate and poor in 13%, 54% and 32%, respectively. Dose titration (DT) to 7
mg twice a day (bid) was performed in 38% and to 10 mg bid in 19% of the
patients. Hypertension was the most common adverse event, (grade (G)3: 39%; G4:
2%). ORR occurred in 32% (n = 33, only partial response). Median PFS, TTF and OS
were 8.3, 5.8 and 16.4 months, respectively. IMDC risk group and DT at 2 weeks
are associated to ORR while grade 3 hypertension is marginally associated. IMDC
risk group and grade 3 hypertension are significantly associated with better PFS,
TTF and OS while DT at 2 weeks is associated to PFS and TTF. CONCLUSION: Efficacy
of axitinib in routine practice is similar to that previously reported, not only
in second- but also in further next-lines of therapy.
PMID- 28511147
TI - Squamous cell carcinoma of the pancreas: A systematic review and pooled survival
analysis.
AB - The diagnosis and treatment of squamous cell carcinoma of the pancreas pose
dilemmas in the clinical practice. The present study was performed according to
the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
guidelines. Eligible articles were sought in MEDLINE up to 30th April 2016. A
pooled Cox regression analysis was performed to evaluate factors potentially
associated with overall survival (OS) and relapse-free survival (RFS). Fifty-four
cases of pure squamous cell pancreatic carcinomas were identified in total. The
mean age was 61.9 years, and most patients were males (61.1%). The median OS was
7 months. Resectability (p = 0.003) and more recent publication year (p < 0.001)
were associated with better OS, as was low/intermediate tumour grade (p = 0.032)
with RFS. Despite its poor prognosis, survival rates of pancreatic squamous cell
carcinoma seem improved during the recent years; resectability and
low/intermediate grade emerged as favourable prognostic factors. Collaborative
epidemiological studies are deemed necessary to further validate the results
stemming from the published case reports of this rare entity.
PMID- 28511148
TI - Computational studies of membrane proteins: from sequence to structure to
simulation.
AB - In this review, I discuss the recent advances in computational approaches to
studying membrane protein structures, covering the latest methods for predicting
a protein structure from its amino acid sequence, through to methods for
assessing the structural dynamics and lipid interactions within molecular
simulations of complex biological membranes. These approaches have not only
benefited from advances in the computational software and architectures, but have
also been assisted by a prodigious rise in the number of both the molecular
sequences and experimentally determined membrane protein structures. The former,
in part stimulated by metagenomics sequencing techniques, has led to an increased
prediction accuracy for the computationally folded protein structures. The
latter, assisted by improvements in structural biology approaches, has led to
longer, larger and more complex molecular simulations of membrane proteins; many
of which have greater relevance to human disease. Here I describe the methods for
predicting a membrane protein structure from sequence, discuss the approaches to
configure membrane protein simulations and detail the techniques used to identify
and characterize specific lipid binding sites to membrane protein structures.
PMID- 28511149
TI - Analysis of extracellular brain chemistry during percutaneous dilational
tracheostomy: A retrospective study of 19 patients.
AB - OBJECTIVE: The purpose of this study was to analyze changes in brain tissue
chemistry around percutaneous dilational tracheostomy (PDT) in patients with
acute brain injury (ABI) in a retrospective single-center analysis. PATIENTS AND
METHODS: We included 19 patients who had continuous monitoring of brain tissue
chemistry and intracranial pressure (ICP) during a 20h period before and after
PDT. Different microdialysis parameters (lactate, pyruvate, lactate pyruvate
ratio (LPR), glycerol and glutamate) and values of ICP, cerebral perfusion
pressure (CPP) and brain tissue oxygenation (PBrO2) were recorded per hour. Mean
values were compared between a 10h period before PDT (prePDT) and after PDT
(postPDT). RESULTS: Mean values of cerebral lactate, pyruvate, LPR, glycerol and
glutamate did not differ significantly between prePDT and postPDT. In addition,
the rate of patients, which exceeded the known threshold was similar between
prePDT and postPDT. Only one patient showed a strong increase of cerebral
glycerol during the postPDT period, but analysis of subcutaneous glycerol could
exclude an intracerebral event. ICP, CPP and PBrO2 did not exhibit significant
changes. CONCLUSIONS: We could exclude the occurrence of cerebral metabolic
crisis and the excess release of cerebral glutamate and glycerol in a series of
19 patients. Our results support the safety of PDT in patients with ABI.
PMID- 28511150
TI - Disparities in cancer stage at diagnosis and survival of Aboriginal and non
Aboriginal South Australians.
AB - BACKGROUND/AIM: This study tested the utility of retrospectively staging cancer
registry data for comparing stage and stage-specific survivals of Aboriginal and
non-Aboriginal people. Differences by area level factors were also explored.
METHODS: This test dataset comprised 950 Aboriginal cases and all other cases
recorded on the South Australian cancer registry with a 1977-2010 diagnosis. A
sub-set of 777 Aboriginal cases diagnosed in 1990-2010 were matched with randomly
selected non-Aboriginal cases by year of birth, diagnostic year, sex, and primary
site of cancer. Competing risk regression summarised associations of Aboriginal
status, stage, and geographic attributes with risk of cancer death. RESULTS:
Aboriginal cases were 10 years younger at diagnosis, more likely to present in
recent diagnostic years, to be resident of remote areas, and have primary cancer
sites of head & neck, lung, liver and cervix. Risk of cancer death was associated
in the matched analysis with more advanced stage at diagnosis. More Aboriginal
than non-Aboriginal cases had distant metastases at diagnosis (31.3% vs 22.0,
p<0.001). After adjusting for stage, remote-living Aboriginal residents had
higher risks of cancer death than Aboriginal residents of metropolitan areas. Non
Aboriginal cases had the lowest risk of cancer death. CONCLUSION: Retrospective
staging proved to be feasible using registry data. Results indicated more
advanced stages for Aboriginal than matched non-Aboriginal cases. Aboriginal
people had higher risks of cancer death, which persisted after adjusting for
stage, and applied irrespective of remoteness of residence, with highest risk of
death occurring among Aboriginal people from remote areas.
PMID- 28511151
TI - Peripheral arteriovenous fistula as vascular access for long-term chemotherapy.
AB - INTRODUCTION: To provide long-term vascular access in clinical oncology
peripheral forearm veins (up to 95% of patients in Ukraine), central venous
access and "complete implanted vascular systems" are used most often. Many
oncology patients have contraindications to catheterization of superior vena
cava. Besides, exploitation of central veins is associated with potential
technical and infectious complications. The aim - to study short-term and long
term results of arteriovenous fistula exploitation as vascular access for
continuous anticancer therapy. MATERIALS AND METHODS: Peripheral venous bed
status in 41 oncology patients taking long-term chemotherapy treatment is
analyzed in the article. Doppler sonography, morphologic and immune histochemical
analyses were used in the study. RESULTS: Doppler sonography found qualitative
and quantitative changes in forearm veins at different time periods after
initiation of chemotherapy in the majority of patients. The major morphologic
manifestations of venous wall damage were chemical phlebitis, local or extended
hardening of venous wall, venous thrombosis and extravasations with necrosis and
subsequent paravasal tissue sclerosis. Alternative vascular access created in 12
patients completely met the adequacy criteria (safety, multiple use, longevity,
realization of the designed therapy program). The conclusion was made about
inapplicability of forearm veins for long-term administration of cytostatic
agents. If it is impossible to use central veins, arteriovenous fistula can
become an alternative vascular access.
PMID- 28511153
TI - [Morbidity rate of obesity in children in ukraine. Overweight as noncontagious
disease risk factor].
AB - INTRODUCTION: The upsurge of prevalence rate of obesity and overweight that in
the majority of cases traces back to childhood is a risk factor of the most
common noncontagious diseases in adults. THE AIM: The aim was to analyze
prevalence of obesity in children in Ukraine and to conduct the pilot study of
medical condition of overweight children. MATERIALS AND METHODS: Official state
statistics of prevalence rate of obesity in kids and screening data of
anthropometric characteristics, arterial tension levels, physical performance
decrement and medical condition of children (boys - 50, girls - 90, average age -
15,1+/-0,1 years) was used in research. Data calculation performed by Statistica
v. 6.0 software. RESULTS: Over the past few decades, the morbidity rate of
obesity in children in Ukraine has greatly increased, especially in year class 15
17. Insufficient diagnosis of obesity in children is the consequence of the
inadequacy of the existing system of preventive care and monitoring survey of
decease risk factors. Children with body mass index (BMI) above normal have a
risk of work decrement in 5,2 times (odds ratio, OR=5,2, CI95%: 1,7-10,6). Such
children have higher risk of development of the diseases of the respiratory
system (OR=8,1; CI95%: 3,9-13,6) and allergic dermatitis (OR=7,7; CI95%: 3,7
12,9). The odds ratio of arterial hypertension in such children is equal to
3,46+/-0,3 (95%CI: 2,0-5,9). CONCLUSIONS: According to prediction calculations,
the situation with the increase of prevalence rate of obesity in children in
Ukraine is unfavorable. The introduction of measures aimed at finding children
with obesity, their registration and monitoring of patients' health with due
regard to decease risk factors at the primary care level would conduce to
improving prevention of obesity and prevention of alimentary diseases
progression.
PMID- 28511154
TI - Cutaneous squamous cell carcinoma: epidemiological aspects among the population
of Ukraine.
AB - INTRODUCTION: In the structure of malignant skin neoplasms, the tumours of
epithelial origin take the first place, among them the prevalence of cutaneous
squamous cell carcinoma (cSCC) is about 20%. The aim of the work involves the
analysis of cSCC epidemiological features among the contingent of the State
Scientific Institution "Scientific and Practical Centre of Preventive and
Clinical Medicine" of the State Administration (SIS) over 2005-2014 (Ukraine,
Kyiv). MATERIAL AND METHODS: For retrospective epidemiological analysis there was
used identifying information of patients with cSCC of the contingent of SIS over
2005-2014 in comparison with the data on patients with cSCC of Kyiv city and Kyiv
region over the same period of time. RESULTS: The morbidity rate of cSCC among
the contingent of SIS in 2005-2014 increased from 6.7 per 100,000people to 37.1
per 100,000 people. Among men it increased from 8.2 per 100,000 people to 59.2
per 100,000 people, and among women - from 6.6 per 100,000 people to 19.2 per
100,000people. Among the contingent of SIS the highest incidence both in men and
women was observed in the age group of 85 and upwards; among men it was 115.2 per
100,000 people, and among women - 112.0 per 100,000 people. CONCLUSIONS: The
morbidity rate of cSCC among the contingent of SIS in 2005-2014 was significantly
higher (p<0.05) than the morbidity rate among the population of Kyiv city and
Kyiv region over the same period of time, with the prevalence of patients aged 85
and upwards, both men and women.
PMID- 28511152
TI - [Pathogenetic substantiation of complex treatment of nonalcoholic steatohepatitis
and steatosis in patients with pre-diabetes and type 2 diabetes].
AB - INTRODUCTION: Thesis is devoted to the optimization of complex treatment of
nonalcoholic steatohepatitis and steatosis in patients with pre-diabetes and type
2 diabetes by acting on carbohydrate and lipid metabolism as well as providing
hepatoprotection. AIM: Optimization of diagnostics and treatment in patients
treatment of nonalcoholic steatohepatitis and steatosis in patients with pre
diabetes and type 2 diabetes. MATERIAL AND METHODS: Examination and treatment of
117 patients with NAFLD and pre-diabetes and type 2 diabetes was performed.
RESULTS: It has been proved that the use of a therapeutic scheme that includes a
balanced diet, taking into account the daily requirement in proteins, fats and
carbohydrates, daily 30-minute walks at a brisk pace, rosuvastatin 10 mg/d, omega
3 PUFA 1000 mg/d and ursodeoxycholic acid 10 mg/kg/d in patients with NAFLD and
pre-diabetes facilitates regression of signs of steatosis. In patients with NAFLD
and type 2 diabetes the above mentioned therapeutic scheme including sitagliptin
100 mg/d promotes regression of steatohepatitis in steatosis. CONCLUSIONS: The
prevalence of nonalcoholic steatohepatitis and liver steatosis in patients with
pre-diabetes has been studied. It has been proved that patients with NAFLD and
pre-diabetes belong to the group with high cardiovascular risk. The features of
metabolic disorders in patients with nonalcoholic fatty liver disease and pre
diabetes or type 2 diabetes were researched. Differentiated treatment schemes of
nonalcoholic steatosis and steatohepatitis in patients with pre-diabetes and type
2 diabetes have been approved for use.
PMID- 28511155
TI - [The role of inflammatory biomarkers in cardiovascular risk stratification].
AB - INTRODUCTION: The increase in cardiovascular diseases requires the search for
ways to predict complications based on research additional to traditional risk
factors, conduct a study of the formation mechanisms of these complications and
to design new treatment strategies. AIM: To get an idea about the relationship
between inflammation in the blood vessels, atherosclerosis and cardiovascular
consequences based on the study of the role of biomarkers of inflammation.
MATERIAL AND METHODS: the literature on the estimation of risk development of
cardiovascular diseases based on the study of the role of biomarkers of vascular
inflammation; bibliographic, a systematic approach. RESULTS: Algorithm
stratification of cardiovascular risk includes a review of the traditional risk
factors for the purpose of preventive therapy. A large number of cases of
cardiovascular events (myocardial infarction, stroke) occurs in bessimptomnom
patients with normal lipid. The use of additional risk factors for development of
cerebral and cardiac disorders will allow to foresee the consequences and to
prevent mortality from cardiovascular disease. Study of the role of inflammation
in development of cardiovascular diseases allows the use of SB and PL-FLA2 as an
important additional cardiovascular markers, independent of traditional risk
factors. CONCLUSIONS: The use of biomarkers LP-FLA2 and SB specific to vascular
inflammation, allows to establish the relationship between endovascular
inflammation, atherosclerosis development and progression of cardiovascular
diseases and to prevent cerebral and cardiac disorders in patients with
traditional risk factor .
PMID- 28511156
TI - The role of the persistent enterovirus infection in development of acute stroke.
AB - INTRODUCTION: The role of enteroviruses in development of dilated cardiomyopathy,
myocardial infarction, myocarditis, pericarditis is known. THE AIM: To examine
the role of chronic enterovirus infections in development of acute stroke.
MATERIAL AND METHODS: Blood samples from 72 patients with acute stroke (study
group) and 35 patients without vascular disease (control group) were investigated
by reverse transcription polymerase chain reaction for the presence of
enterovirus RNA, by using virological method to detect enteroviruses, by ELISA
for the levels of IgM and IgG antibodies to enteroviruses. RESULTS: The
enteroviruses genomes were detected significantly often in the serum of patients
with stroke (23,6 +/- 5,9%) than in control group (2,9 +/- 2,8%). The viruses
were isolated and were identified as Coxsackie B (serotypes 2, 3, 4) and ECHO
(serotypes 6, 9, 27 (two strains), 29), three strains have not been identified in
study group. IgM to enteroviruses were not found in the sera of both groups of
patients. IgG to enteroviruses were detected in 17 patients in study group (23,6
+/- 5,9%) and 2 patients in control group (5,7 +/- 3,9%). The presence of
enteroviruses genomes and IgG in sera of patients in control group (11,1 +/-
3,7%) indicate the persistence of enteroviruses. The proportion of patients with
IgG to enteroviruses in sera is higher in study group (12,5 +/- 3,9%) than in
control group (5,7 +/- 3,9%). CONCLUSION: The enterovirus infections play trigger
role in development of acute stroke.
PMID- 28511157
TI - [Conceptual approaches to improve the system of preventive medical examinations
of the adult population].
AB - INTRODUCTION: Health indicators Ukraine's adult population over the last decade
still too high for both countries of the European Community. Features direction
of preventive health system of Ukraine, currently used extremely limited.
Existing approaches to planning and carrying out preventive medical examinations
in our country are outdated and are formal, so improving the existing system of
preventive medical examinations of the adult population is necessary and timely.
AIM: To prove scientifically conceptual approaches to improving the planning and
implementation of preventive medical examinations of adults through functional
and structural changes. MATERIALS AND METHODS: Literature review, system analysis
and conceptual modeling method. RESULTS: The analysis of the experience of our
country for the prevention of the most common diseases and the state of the
resource base for its conduct theoretically grounded and presented, functional
structural model of preventive medical examinations of the adult population,
based on are: phasing of checkups, the introduction of sex and age of maps,
determination at increased risk of diseases and the establishment / improvement
of the automated monitoring systems of risk factors for noncommunicable diseases.
CONCLUSIONS: Carrying out preventive medical examinations of the adult population
using gender and age card allows you to choose the most appropriate preventive
measures and to pay particular attention to preventive measures aimed at
preventing the leading causes of disease and disability in a particular age
group.
PMID- 28511158
TI - Evolution of some indicators of systemic immunity in patients with acne while
using laser therapy.
AB - INTRODUCTION: One of the important problems in modern dermatology is to improve
treatment efficiency of acne being a common cause for cicatricial skin changes,
loss of performance capability and social activity and negatively affects the
psycho-emotional state of patients and their quality of life. The topicality of
the disease is due to the high degree of its proliferation, chronic and recurrent
course, and resistance to existing therapies. Reducing the effectiveness of skin
diseases treatment, including that of acne, at present, is associated with
developing resistance to drugs, which causes the use of non-drug methods in
dermatology nowadays, including low-intensity laser therapy. Objective - to
determine evolution of the systemic immunity indices in patients with acne with
different degrees of severity in the course of a standard and comprehensive
treatment by laser therapy. MATERIALS AND METHODS: We observed 77 patients with
acne aged 18-25 years; 32 of them received standard therapy, other 45 patients
were additionally prescribed combined (superficial venous and external) laser
therapy. We determined the indices of all patients' systemic immunity using well
known techniques. RESULTS: It has been established, that using laser therapy in
comprehensive treatment of patients with acne promotes the normalization or a
tendency to normalization of the systemic immunity and phagocytosis with
significant difference between the indices of the individuals who received a
standard therapy alone.
PMID- 28511159
TI - Effect of apple polyphenol concentrate on lipid metabolism in rats under
experimental insulin resistance.
AB - INTRODUCTION: Obesity is strongly associated with an increased risk of developing
insulin resistance as the metabolic indicator of prediabetes and a major risk
factor in diabetes mellitus type 2 pathogenesis. Medicinal products obtained from
apples can be used as potent prophylactic and therapeutic remedies in treatment
of diabetes mellitus. AIM: Experiment was designed to study the effect of total
apple polyphenol food concentrate on lipid metabolism under experimental IR.
MATERIALS AND METHODS: Male Wistar rats weighting 180-210 g were used in the
experiment. IR was induced by high-calorie diet enriched with fructose. The
effect of total apple polyphenol food concentrate was compared with the action of
epigallocatechin gallate and quercetin. To estimate the alterations in lipid
metabolism in liver homogenate were measured triacylglycerols, free fatty acids,
total phospholipids, TBA-reactive substance and conjugated dienes contents. In
blood serum were measured total lipids, triacylglycerols, cholesterol, total
phospholipids and reduced glutathione levels. RESULTS: The obtained results
indicated that feeding rats with high-calorie diet enriched with fructose caused
the dyslipidemia and oxidative stress development. The administration of
quercetin, epigallocatechin gallate and total apple polyphenol food concentrate
improved disorders of lipid metabolism and pro-oxidant-antioxidant homeostasis.
CONCLUSIONS: Total apple polyphenol food concentrate had a more pronounced effect
on studied indices that is probably due to synergism and additive effect of
extract numerous components.
PMID- 28511160
TI - Features of some clinical examination parameters in patients with psoriatic
arthritis.
AB - INTRODUCTION: The relationship of cause-and-effect mechanisms of exacerbation and
progressing with defining of the role of stress reaction in the psoriatic
arthritis (PA) development has been examined in the article by analyzing the
characteristics of medical history, current dynamics as well as clinical,
instrumental and laboratory examinations. The objective was to study the role of
basic indices of laboratory examinations of patients used clarify their role in
the pathogenesis of PA. MATERIALS AND METHODS: The concentration of trigger
cytokines - IL-1beta, IL-8, IL-17, IL-22, stress hormones - ACTH and cortisol,
state of cell-antibody mediated immunity (CD3+, CD4+, CD8+, CD16+, CD22+, IRI,
IgM, IgG levels) in the serum of patients were defined. RESULTS AND DISCUSSION:
We have detected the possible changes of stress-reaction mediator concentrations
in the serum of patients with PA (i.e. decreasing of the status of cell immunity
indices (CD3+, CD4+, CD8+ T- lymphocytes, V- lymphocytes CD22+ fraction, IRI with
compensatory increasing of the levels of CD16+ T-cells, cytokines - IL-1 beta, IL
8, IL-17, IL-22, stress hormone - cortisol, immunoglobulins IgM, IgG, CIC)
irrespective of the disease duration which testifies the strain of their stress
realising mechanisms, even if clinical stabilization of skin and joint process is
normalized. CONCLUSIONS: Thus, the final diagnosis of PA is determined only under
aggregation of anamnestic, clinical, instrumental and laboratory data and the
results of additional examinations. The indices mentioned above are key mediators
of stress-realizing immune-neuroendocrine system and play an ambiguous role in
the development of PA, their various effects require further study.
PMID- 28511161
TI - [The diagnostics and clinical pattern of nonalcoholic fatty liver disease in
patients with pre-diabetes and type 2 diabetes and obesity].
AB - INTRODUCTION: The data of epidemiological researches confirm the tendency in
increasing of non alcoholic fatty liver disease (NAFLD) in patients with insulin
resistance which occurs because of obesity, diabetes type 2 and metabolic
syndrome. AIM: Optimization of diagnostic and treatment efficacy in patients with
non alcoholic steatosis and steatohepatitis on the background of obesity.
MATERIALS AND METHODS: General clinical examination of patients, laboratory and
instrumental methods ( fatty liver index, non invasive assessment of liver,
morphology, electrocardiography, treadmillergometry, ultrasound examination of
abdominal organs, liver elastography,CT,MRI, methods of statistical analysis.
RESULTS: NAFLD was diagnosed in 98.4% of patients with diabetes type 2, from
which steatosis was found in 54.84% and steatohepatitis in 45.16%. In individuals
with prediabetes NAFLD was in 70.5%, of which 85.45% with steatosis and 14.55%
steatohepatitis (p<0.05). The clinical picture of patients with NAFLD prevailed
such symptoms and complaints: flatulence in 43.59% of patients, weakness and pain
in the right upper quadrant in 29.9% of patients. Fewer patients complained on
discomfort in abdomen 28.21%, constipation 21.37% and feeling of bitterness in
the mouth 21.37%. CONCLUSION: Clinical features of NAFLD are polysymptomatic.
There are prevalence of dyspeptic syndromes (bloating met in 43.59% of patients,
pain in right upper quadrant and discomfort in abdomen -29.91%, constipation-
28.21%, bitterness in mouth-21.37%. Determination of fatty liver index is very
informative method of screening patients with hepatisteatosis.
PMID- 28511162
TI - Improvement of the complex medical treatment for the patients with chronic
biliary pancreatitis.
AB - INTRODUCTION: The most common reason of chronic pancreatitis is liver and bile
ducts disease: functional disorders, chronic cholecystitis, cholelithiasis and
cholecystectomy in medical history. All these changes are associated with the
colloidal structure of bile, increased lithogenicity, gallstones formation,
Oddi's sphincter dysfunction, dysmotility and inflammation in the bile ducts. THE
AIM: to study the effectiveness of using medicine Liveria IC (metadoxine) in
standard therapy as well as effect on spectrum of blood serum lipids and
structural condition of liver (stiffness) and pancreas in patients with chronic
biliary pancreatitis combined with obesity. MATERIALS AND METHOD: 115 patients
suffering from chronic biliary pancreatitis and obesity were the subjects of the
study. They were compared to etiological factor socioeconomic conditions and
nutrition (regular food 5 times a day without aggressive food (fatty, spicy,
sour, fried products)). Also the effect of the alcohol factor was excluded.
RESULTS: The obtained decrease in stiffness of the liver and pancreas indicates
an improvement of their structural state. CONCLUSIONS: Using medication LiveriaIC
(metadoxine) as the part of the complex therapy for the patients who are
suffering from CBP combined with obesity gives some improvement of the lipid
profile indices and the structural condition of liver and pancreas (according to
the data of SWE) (r<0.05).
PMID- 28511163
TI - [Impact of physical activity on anthropometric indices in patients with
nonalcoholic fatty liver disease and pre-diabetes or type 2 diabetes].
AB - INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is currently the most
common cause of chronic liver disease in many developed countries. The first
step, which is offered to all patients with NAFLD includes lifestyle
modifications, low-calorie diet, increased physical activity and giving up
smoking. OBJECTIVE: to evaluate the efficiency of the daily 30-minute walking at
a fast pace on the dynamics of anthropometric indices in patients with NAFLD and
pre-diabetes or type 2 diabetes. MATERIALS AND METHODS: The study included 59
patients with nonalcoholic fatty liver disease and impaired carbohydrate
metabolism, which conducted a comprehensive clinical examination that included
collection of anthropometric data, physical examination and taking venous blood
for laboratory analysis, ultrasound of the abdomen. RESULTS: According to
statistical analysis, patients on the background of NAFLD and pre-diabeetes /
type 2 diabetes, performing daily 30-minute walks at a fast pace, found
significant changes of anthropometric indices. CONCLUSIONS: Daily 30-minute
walking at a fast pace is an effective method on reduction of body weight in
patients with NAFLD and pre-diabetes or type 2 diabetes.
PMID- 28511164
TI - Changes of lipidic and the immunological state at patients with a metabolic
syndrome in Ukraine.
AB - INTRODUCTION: The metabolic syndrome has become pandemic nature and tends to
rejuvenation in the world. Elucidation of the pathogenic mechanisms on membrane
cell level will optimize the treatment of patients with metabolic syndrome and
prevention of metabolic syndrome on the level of pre-clinical manifestations.
AIM: to study the immunological status and lipid metabolism in the patients with
metabolic syndrome and the pathogenetic mechanisms of metabolic syndrome were
established. MATERIAL AND METHODS: There were 4 groups of pacients (110) with:
metabolic syndrome, ischemic heart disease and hypertension, hypertention;
control group. General clinical, instrumental, laboratory and statistical methods
were used. RESULTS: The levels of immune factors - interleukin-6 in supernatants
of mononuclear cells by 65%, sICAM-1 by 20% is elevated in patients with
metabolic syndrome compared with the control group. The increasing of the content
of saturated fatty acids by 9.4% and polyunsaturated fatty acid by 36.6% lead to
fundamental breach of structural and functional properties of membranes. There is
significant common carotid artery intima media thickness on average twice at the
patients with metabolic syndrome and with ischemic heart disease and
hypertension. CONCLUSIONS: The immunoinflammatory reactions were more revealed in
the group of patients with metabolic syndrome than in other groups. The lipid
state at patients with metabolic syndrome was changed more than in patients with
hypertension or patients with ischemic heart disease and hypertension both.
Moreover our data indicate the presence of structural changes in the vessel wall
in patients with metabolic syndrome.
PMID- 28511166
TI - Features of the immunohistochemical characteristics of primary tumors and
recurrences of breast cancer after radical treatment.
AB - INTRODUCTION: Appearance of Recurrence (RC) of breast cancer (BC) is associated
with a high risk of distant metastases, needs re-treatment and indicates the
tumor aggressiveness. It has been remained unclear the molecular characteristics
both of the RC and primary tumors in patients with invasive forms of breast
cancer after mastectomy by Madden. THE AIM: To explore the changing of the
receptor status of the primary tumor and local RC in patients with breast cancer.
MATERIALS AND METHODS: Immunohistochemical study were conducted on 262 patients
with invasive breast cancer. Patients were divided into two groups: only local RC
- 131 women and primary tumors of patients without local RC - also 131 persons.
RESULTS: The difference of the receptor status of the tumors is presented. In the
group of patients with recurrent "triplet negative" cancer and patients with
positive reaction of epidermal growth factor (HER2neo) is more than 15.2%. In
patients where RC (control group in the study) was not observed we have the mass
greater proportion of tumors with positive hormone receptors in various
combinations. CONCLUSIONS: Relapses are accompanied by lower levels of hormone
receptors and increasing the frequency of "triplet negative" cancer as well as
increasing of epidermal growth factor.
PMID- 28511165
TI - Susceptibility of streptococcus pneumoniae to fluoroquinolones and macrolides in
upper respiratory tract infections.
AB - INTRODUCTION: Streptococcal species are known as the most common cause of
bacterial upper respiratory tract infections (URTI). Once bacterial infection is
diagnosed it demands empirical antibiotic prescription. On the other hand
antimicrobial resistance is a global burden in today's medicine. For that reason,
knowing of antimicrobial susceptibility patterns in population is an important
background for successful treatment of bacterial caused URTI. The aim of this
study was to analyze S. pneumoniae resistance and susceptibility patterns to
fluoroquinolones and macrolides in URTI. MATERIALS AND METHODS: The results of
microbiological examination of 2,055 pharyngeal swabs taken from patients with
bacterial caused tonsillitis, pharyngitis and laryngitis were analyzed.
Antimicrobial susceptibility testing for levofloxacin, ofloxacin, gatifloxacin,
erythromycin, clarithromycin, azithromycin was performed with the disk-diffusion
method. RESULTS: The incidence of S. pneumoniae in the etiological structure of
bacterial caused URTI was increasing from 22.47% of cases in 2011 to 36.48% in
2015. The susceptibility of this microorganism to ofloxacin, gatifloxacin and
levofloxacin decreased from 96.25%, 100% and 95.00% in 2011 to 44.22%, 65.99% and
62.59% in 2015 respectively. The susceptibility of S. pneumoniae to erythromycin,
azithromycin and clarithromycin also decreased from 30.00%, 63.75% and 41.25% in
2011 to 6.80%, 26.53%, 27.21 in 2015. CONCLUSIONS: Among investigated antibiotics
levofloxacin can be recommended for empiric therapy of URTI because of high
pneumococci susceptibility to this drug.
PMID- 28511167
TI - Gut microbiota changes as a risk factor for obesity.
AB - INTRODUCTION: The number of obese people in recent decades is increasing
significantly. Among the many aspects of obesity in the last decade, the role and
importance of changes in the gut microbiota (GM) attracts special attention. The
aim of the review was to analyze the results of studies, focused on the role of
gut microbiota in the obesity development. MATERIALS AND METHODS: Screening was
conducted on 33 researches, which examined the role of the gut microbiota balance
in the development of obesity. Among them, 13 studies were selected for more
detailed analysis. RESULTS: Obesity revealed typical changes in GM: an increase
in the number of microbes of the genus Firmicutes and a decrease in the number of
microbes of the genus Bacteroeidetes, which is particularly vividly demonstrated
by studies of rodents. In obese mice, the microfamilies of the genus Firmicutes
account for 80% of all GM (in control animals 60%), and the number of
microorganisms of the genus Bacteroeidetes decreases by half (from 40 to 20%),
compared to mice with normal weight. CONCLUSION: Despite the complexity of the
question of the relationship between GM and obesity, the totality of the data
received, especially the results of experimental studies, affirm the thesis that
changes in GM may contribute to the development of obesity.
PMID- 28511169
TI - Efficiency comparison of tofacitinib and budesonid in treatment of nonspecific
ulcerative colitis.
AB - INTRODUCTION: A constant interest to explore NUC is caused by the global trend
showing a rise in colitis mobidity rate. According to a series of epidemiological
studies, the highest incidence of NUC occurs in young age groups, which leads to
significant loss of working capacity and high level of incapacitation. One of the
leading roles in the pathogenesis of this disease is reportedly played by
immunogenetic theory. To date, the main practical technique of NUC diagnostics is
colonoscopy. To assess the activity level, the Mayo score is used most
frequently. The aim of NUC treatment is to achieve and maintain remission as well
as improve the patients' life quality. One of the main achievements of
contemporary gastroenterology is practical introduction of such high-performance
preparations as mononuclear antibodies to TNF- alpha. AIM: To compare the impact
of tofacitinib and budesonid on the mucous membrane of NUC patients. MATERIAL AND
METHODS: Over the past two years 498 colonoscopic surveys have been performed at
the Therapeutics Department of Uzhhorod Central Rayon Hospital, of which 16
patients have been chosen. Depending upon the treatment obtained, all the
patients were divided into two groups: Group I - patients that were taking
tofacitinib in constant doses of 10 mg/day; Group II - patients that were taking
budesonid in doses of 9 mg/day. The Mayo score was used to assess the level of
inflammation activity. RESULTS: By morbidity occurrence, proctosigmoiditis was
diagnosticated in 5 (31.25%), sinistral colitis in 7 (43.75%), and total colitis
in 4 (25.00%) patients. The values of the integrative Mayo index at the moment of
primary examination were 8.89+/-1.17 and 8.29+/-1.11 in Groups I and II,
correspondingly. The treatment with budesonid led to a 15.56% decline in
inflammation activity, equaling to 7.00+/-1.15 points of the Mayo score. In
response to the treatment with tofacitinib the value went down by 59.96%,
equaling to 3.56+/-1.13 points of the Mayo score, which was reliably lower as
compared with Group II ( r<0.05). CONCLUSIONS: The use of tofacitinib was
observed to result in a reliably better curative effect as compared with
budesonid, which fact was verified endoscopically.
PMID- 28511168
TI - [The nonalcoholic steatohepatitis influence on the course and progression of
ischemic heart disease].
AB - INTRODUCTION: Nonalcoholic steatohepatitis (NASH) can be considered a risk factor
of progression of diseases associated with atherosclerosis, especially ischemic
heart disease (IHD) with a high probability of early myocardial infarction (MI).
AIM: To study the peculiarities and nature of ischemic heart disease clinical
picture in patients with concomitant NASH. MATERIALS AND METHODS: The study
involved 58 patients with ischemic heart disease. The nature of ischemic heart
disease according to outpatients was evaluated, an assessment of ECG,
echocardioscopy changes and Holter-monitoring was performed. RESULTS: The
ischemic heart disease and concomitant NASH was observed only in young and middle
age patients, among whom 16 (61.5%) revealed the presence of visceral obesity
type. The presence of this synthropy is accompanied by an aggressive course of
coronary heart disease with early MI development. According to Seattle Angina
Questionnaire scale is case of IHD with NASH combination more limitation of
physical activity, less pleasure treatment, worse perception of the disease and a
significant reduction in the life quality of patients were noted. The nature of
myocardium bioelectric activity disorders did not differ in the comparison group
and matched the angina functional class and myocardial infarction consequences.
CONCLUSIONS: The presence of visceral obesity, NASH causes early and aggressive
course of ischemic heart disease, which is accompanied by a high risk of MI and
reduces the patients' quality of life.
PMID- 28511170
TI - Mosaic Trisomy 9p in a Patient with Mild Dysmorphic Features and Normal
Intelligence.
AB - To the Editor: Partial and whole duplications of the short arm of chromosome 9
have been commonly reported in the literature with characteristic phenotypic
features and intellectual disabilities. The clinical features of 9p duplications
are broad and can include growth retardation, developmental delay, intellectual
disability, microbrachycephaly, deep set eyes, hypertelorism, downslanting
palpebral fissures, prominent nasal root, bulbous nasal tip, low-set ears, short
fingers and toes with hypoplastic nails, and delayed bone age (Bonaglia et al.,
2002; Zou et al., 2009; Guilherme et al., 2014).
PMID- 28511171
TI - Clinical Outcome of Patients with Raised Intraepithelial Lymphocytes with Normal
Villous Architecture on Duodenal Biopsy.
AB - INTRODUCTION: The finding of a raised intraepithelial lymphocytes (IELs) count
with normal villous architecture is of sufficient clinical importance to be
reported in routine duodenal biopsies. AIM: To study the clinical and demographic
data of patients with isolated increased IELs on duodenal biopsy. METHODS: A
single-tertiary-centre retrospective study was carried out with a review of
medical records of patients with increased IELs. Patients from 2012 to 2014, >18
years with at least one biopsy from the second part of the duodenum with
increased IELs; defined as >25 IELs/100 enterocytes, with preserved villous
architecture were identified from our histopathology database with exclusion of
patients with coeliac disease (CD).Clinical and demographic data were recorded
following a chart review. CD was diagnosed by the attending physician based on
the Physician Global Assessment. Data was compared between groups using a Student
t test and ORs were calculated as appropriate. Statistical significance was set a
priori at p < 0.05. RESULTS: Over 24 months, 6,244 patients were found to have
duodenal biopsies and 114 (1.8%) had isolated increased IELs. Of the patients
with increased IELs, the mean age was 50 years and 34 (30%) were male. Follow-up
was available in 75 (65%) of these and CD was subsequently diagnosed in 32% (n =
24). CD was associated with the female gender (22 out of 24 vs. 39 out of 51, OR
7.5, older age 55 vs. 41 years, p < 0.04), and higher IEL count with an IEL of
>40 in 11 out of 24 (46%) with CD vs. 12 out of 51 (24%) without CD, p = 0.0006.
CONCLUSION: It is a non-specific but important finding, as it can have clinical
implications.
PMID- 28511173
TI - Is Occupational Complexity Associated with Cognitive Performance or Decline?
Results from the Australian Longitudinal Study of Ageing.
AB - BACKGROUND: Long-term protective associations proposed between previous complex
occupational tasks and cognitive functioning in later life point to work roles
contributing to cognitive reserve. OBJECTIVE: To examine occupational complexity
involving data, people, and things in relation to the level of, and rate of
change in, cognitive functioning. METHODS: Participants were 1,290 members of the
Australian Longitudinal Study of Ageing and initially aged 65-102 years (mean =
79). Information about main lifetime occupation was collected retrospectively.
Cognition was assessed 4 times over a 13-year interval. RESULTS: In multilevel
models adjusted for demographics, medical conditions, and depressive symptoms,
higher complexity involving data was associated with faster speed (beta = 0.73, p
< 0.001), better memory (beta = 0.32, p < 0.05), and mental status (beta = 0.40,
p < 0.001) at baseline. These associations remained statistically reliable after
adjusting for complexity with people and things, sedentary and heavy physical
work, retirement age, and leisure activity. Complexity with things was associated
with slower speed (beta = -0.50, p < 0.001) and poorer mental status (beta =
0.26, p < 0.01) and was not explained by other variables. There were no
associations of occupational complexity with rates of cognitive decline over
time. CONCLUSION: Older individuals retired from occupations characterized by
higher complexity with data maintain their cognitive advantage over those with
lower complexity into older adulthood, although without additional moderation of
this advantage in terms of less postretirement cognitive decline. Complexity of
work with things confers a negative relation to cognition whilst also not
affecting postretirement cognitive change. Although the relative contributions of
occupation or other early life influences for cognition remain to be established,
it nevertheless may be beneficial to promote workplace design strategies and
interventions that incorporate complex activities, particularly tasks involving
data.
PMID- 28511172
TI - Donor-Specific Anti-Human Leukocyte Antigens Antibodies, Acute Rejection, Renal
Function, and Histology in Kidney Transplant Recipients Receiving Tacrolimus and
Everolimus.
AB - BACKGROUND: This analysis compared efficacy, renal function, and histology in
kidney transplant recipients receiving tacrolimus (TAC) combined with everolimus
(EVR) or mycophenolate (MPS). METHODS: This was a retrospective analysis from a
randomized trial in kidney transplant recipients who received a single 3 mg/kg
dose of rabbit antithymocyte globulin (r-ATG), TAC, EVR, and prednisone (PRED; r
ATG/EVR, n = 85), basiliximab (BAS), TAC, EVR, and PRED (BAS/EVR, n = 102) or
BAS, TAC, MPS, and PRED (BAS/MPS, n = 101). We evaluated the incidence of de novo
donor-specific anti-human leukocyte antigens antibodies (DSA) and histology on
protocol biopsies at 12 months, and the incidence of acute rejection, estimated
glomerular filtration rate (eGFR) and proteinuria at 36 months. RESULTS: At 12
months, there were no differences in de novo DSA (6.4 vs. 3.4 vs. 5.5%) or in
subclinical inflammation (2.0 vs. 4.8 vs. 10.2%), interstitial fibrosis/tubular
atrophy (57.1 vs. 58.5 vs. 53.8%) and C4d deposition (2.0 vs. 7.3 vs. 2.6%). At
36 months, there were no differences in the incidence of treatment failure (19.0
vs. 27.7 vs. 27.7%, p = 0.186), first biopsy-proven acute rejection (9.5 vs. 21.8
vs. 16.8%, p = 0.073), and urine protein/creatinine ratios (0.53 +/- 1.05 vs.
0.62 +/- 0.75 vs. 0.71 +/- 1.24). eGFR was lower in the BAS/EVR compared to that
in the BAS/MPS group (53.4 +/- 20.9 vs. 50.8 +/- 19.5 vs. 60.7 +/- 21.2
mL/min/1.73 m2, p = 0.017) but comparable using a sensitive analysis (49.5 +/- 23
vs. 47.5 +/- 22.6 vs. 53.6 +/- 27.8 mL/min/1.73 m2, p = 0.207). CONCLUSION: In
this cohort, the use of EVR and reduced TAC concentrations were associated with
comparable efficacy, renal function, and histological parameters compared to the
standard-of-care immunosuppressive regimen.
PMID- 28511174
TI - Noninvasive Prenatal Detection of Trisomy 21 by Targeted Semiconductor
Sequencing: A Technical Feasibility Study.
AB - OBJECTIVE: To develop an alternate noninvasive prenatal testing method for the
assessment of trisomy 21 (T21) using a targeted semiconductor sequencing
approach. METHODS: A customized AmpliSeq panel was designed with 1,067 primer
pairs targeting specific regions on chromosomes 21, 18, 13, and others. A total
of 235 samples, including 30 affected with T21, were sequenced with an Ion
Torrent Proton sequencer, and a method was developed for assessing the
probability of fetal aneuploidy via derivation of a risk score. RESULTS:
Application of the derived risk score yields a bimodal distribution, with the
affected samples clustering near 1.0 and the unaffected near 0. For a risk score
cutoff of 0.345, above which all would be considered at "high risk," all 30 T21
positive pregnancies were correctly predicted to be affected, and 199 of the 205
non-T21 samples were correctly predicted. The average hands-on time spent on
library preparation and sequencing was 19 h in total, and the average number of
reads of sequence obtained was 3.75 million per sample. CONCLUSION: With the
described targeted sequencing approach on the semiconductor platform using a
custom-designed library and a probabilistic statistical approach, we have
demonstrated the feasibility of an alternate method of assessment for fetal T21.
PMID- 28511175
TI - Flexible 19-Gauge Endobronchial Ultrasound-Guided Transbronchial Needle
Aspiration Needle: First Experience.
AB - BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration
(EBUS-TBNA) is a well-established first-line invasive modality for mediastinal
lymph node staging in lung cancer patients and in the diagnostic workup of
patients with mediastinal adenopathy. With the current 21- and 22-gauge (G) EBUS
TBNA needles, the procedure can be limited by the degree of flexibility in the
needle and the size of the lumen in tissue acquisition. OBJECTIVE: We report our
initial experience with a first-generation flexible 19-G EBUS-TBNA (Flex 19G;
Olympus Respiratory America, Redmond, WA, USA) needle with regards to efficacy
and safety. METHODS: The Flex 19G EBUS-TBNA needle was used in 47 selected
patients with enlarged hilar and/or mediastinal lymphadenopathy at 3 centers. The
standard Olympus EBUS scope with a 2.2-mm working channel was used in all cases.
RESULTS: The diagnostic yield of the Flex 19G needle according to clinical
cytopathology reports was 89% (42/47). The diagnosis and their respective
diagnostic yield with the Flex 19G EBUS-TBNA needle were malignancy 24/27 (89%),
sarcoidosis 13/14 (93%), and reactive lymph node hyperplasia 5/6 (83%). The mean
short axis of the sampled lymph nodes was 19 +/- 9 mm. No complications occurred
except for 1 instance of moderate bleeding, which did not require intervention
beyond suctioning and subsequently resolved. All 13 patients diagnosed with
adenocarcinoma by the 19-G needle had sufficient tissue for genetic testing.
CONCLUSION: EBUS-TBNA using the first-generation Flex 19G needle is feasible and
safe with promising diagnostic yield while providing a greater degree of flexion
with the Olympus EBUS scope. Additional clinical evaluations are warranted.
PMID- 28511176
TI - Aging and the Inevitable Limit to Human Life Span.
AB - There is a long-lasting debate about a natural limit to human life span, and it
has been argued that the maximum reported age at death, which has not increased
for ca 25 years, fluctuates around 115 years, even if some persons live beyond
this age. We argue that the close connection of species-specific longevity with
life history strategies explains why human life span is limited and cannot reach
the considerably longer life spans of several other species.
PMID- 28511177
TI - Familial Hyperkalemia and Hypertension (FHHt) and KLHL3: Description of a Family
with a New Recessive Mutation (S553L) Compared to a Family with a Dominant
Mutation, Q309R, with Analysis of Urinary Sodium Chloride Cotransporter.
AB - BACKGROUND: Familial hyperkalemia and hypertension (FHHt) is an inherited
disorder manifested by hyperkalemia and hypertension. The following four
causative genes were identified: WNK1, WNK4, CUL3, and KLHL3. For the first 3
genes, inheritance is autosomal dominant. For KLHL3, inheritance is mostly
dominant. A few cases with autosomal recessive disease were described. The
mechanism of these 2 modes of inheritance is not clear. In the recessive form,
the phenotype of heterozygotes is not well described. METHODS: Clinical and
genetic investigation of members of 2 families was performed, one with recessive
FHHt, and the other, an expansion of a family with Q309R KLHL3 dominant mutation,
previously reported by us. Urinary exosomal sodium chloride cotransporter (NCC)
was measured. RESULTS: A family with recessive FHHt caused by a new KLHL3
mutation, S553L, is described. This consanguineous Jewish family of Yemenite
extraction, included 2 homozygous and 7 heterozygous affected subjects. Increased
urinary NCC was found in the affected members of the family with dominant Q309R
KLHL3 mutation. In the recessive S553L family, homozygotes appeared to have
increased urinary NCC abundance. Surprisingly, heterozygotes seemed to have also
increased urinary NCC, though at an apparently lower degree. This was not
accompanied by a clinical phenotype. CONCLUSIONS: A new recessive mutation in
KLHL3 (S553L) was identified in FHHt. Increased urinary NCC was found in affected
members (heterozygous) with dominant KLHL3 Q309R, and in affected members
(homozygous) of the recessive form. Unexpectedly, in the recessive disease,
heterozygotes seemed to have increased urinary NCC as well, apparently not
sufficient quantitatively to produce a clinical phenotype.
PMID- 28511178
TI - Descriptions of Apoplexy by Joseph Frank in the Beginning of the Nineteenth
Century in Vilnius.
AB - In the beginning of the 19th century, apoplexy was understood to be a disease of
the cerebral blood vessels, manifesting with a sudden weakening or extinction of
sensation and the patient's inability to move. In this study, we examined the
situation of neurology in the beginning of the 19th century in Vilnius through
the perspective of a nervous system disease - apoplexy. Case reports and
descriptions of apoplexy in the textbook and memoirs by Joseph Frank (1771-1842),
descriptions of patients with apoplexy from the proceedings of Vilnius University
Clinic were analysed. It was identified that the main cause of apoplexy was not
an imbalance of the four humours but the pathology of cerebral blood vessels.
However, following ancient tradition, the principles of recreation and moderation
were thought to be important for the prevention of apoplexy, and bloodletting and
diet were believed to be essential for the treatment.
PMID- 28511179
TI - Vascular Access in the Elderly: Does One Size Fit All?
PMID- 28511180
TI - Response Predictors of S-1, Cisplatin, and Docetaxel Combination Chemotherapy for
Metastatic Gastric Cancer: Microarray Analysis of Whole Human Genes.
AB - OBJECTIVES: The aim of this study was to identify biomarkers for predicting the
efficacy of docetaxel, cisplatin, and S-1 (DCS) therapy for advanced gastric
cancer using microarrays of biopsy specimens before chemotherapy. METHODS:
Nineteen samples were taken from 19 patients with unresectable metastatic gastric
cancer who received DCS as a first-line therapy. Laser capture microdissection
was performed, and total cellular RNA was extracted from each microdissected
sample. Whole-gene expression was analyzed by microarray, and the difference in
mRNA expression observed with the microarrays was confirmed by quantitative real
time PCR. Immunohistochemical staining was performed using clinical tissue
sections obtained by endoscopic biopsy. RESULTS: Eleven patients were identified
as early responders and 8 patients as nonresponders to DCS therapy. Twenty-nine
genes showed significant differences in relative expression ratios between tumor
and normal tissues. A classifier set of 29 genes had high accuracy (94.7%) for
distinguishing gene expression between 11 early responders and 8 nonresponders.
Decreasing the size of the classifier set to 4 genes (PDGFB, PCGF3, CISH, and
ANXA5) increased the accuracy to 100%. Expression levels by real-time PCR for
validation were well correlated with those 4 genes in microarrays. CONCLUSION:
The genes identified may serve as efficient biomarkers for personalized cancer
targeted therapy.
PMID- 28511181
TI - 1-CMDb: A Curated Database of Genomic Variations of the One-Carbon Metabolism
Pathway.
AB - BACKGROUND: The one-carbon metabolism pathway is vital in maintaining tissue
homeostasis by driving the critical reactions of folate and methionine cycles. A
myriad of genetic and epigenetic events mark the rate of reactions in a tissue
specific manner. Integration of these to predict and provide personalized health
management requires robust computational tools that can process multiomics data.
The DNA sequences that may determine the chain of biological events and the
endpoint reactions within one-carbon metabolism genes remain to be
comprehensively recorded. Hence, we designed the one-carbon metabolism database
(1-CMDb) as a platform to interrogate its association with a host of human
disorders. METHODS: DNA sequence and network information of a total of 48 genes
were extracted from a literature survey and KEGG pathway that are involved in the
one-carbon folate-mediated pathway. The information generated, collected, and
compiled for all these genes from the UCSC genome browser included the single
nucleotide polymorphisms (SNPs), CpGs, copy number variations (CNVs), and miRNAs,
and a comprehensive database was created. Furthermore, a significant correlation
analysis was performed for SNPs in the pathway genes. RESULTS: Detailed data of
SNPs, CNVs, CpG islands, and miRNAs for 48 folate pathway genes were compiled.
The SNPs in CNVs (9670), CpGs (984), and miRNAs (14) were also compiled for all
pathway genes. The SIFT score, the prediction and PolyPhen score, as well as the
prediction for each of the SNPs were tabulated and represented for folate pathway
genes. Also included in the database for folate pathway genes were the links to
124 various phenotypes and disease associations as reported in the literature and
from publicly available information. CONCLUSION: A comprehensive database was
generated consisting of genomic elements within and among SNPs, CNVs, CpGs, and
miRNAs of one-carbon metabolism pathways to facilitate (a) single source of
information and (b) integration into large-genome scale network analysis to be
developed in the future by the scientific community. The database can be accessed
at http://slsdb.manipal.edu/ocm/.
PMID- 28511182
TI - Cannabis Use among People Entering Drug Treatment in Europe: A Growing
Phenomenon?
AB - This paper explores European and national trends in specialised drug treatment
entry for cannabis-related problems. The analysis is based on data for the years
2003-2014 from 22 European countries. Between 2003 and 2014, the overall number
and proportion of primary cannabis-related first-time entrants increased
significantly. A joinpoint regression analysis indicates that the overall
increase of cannabis treatment entries is continuous, although country-related
differences are observed. Possible explanations for the increase and different
time trends are discussed including an increase in cannabis prevalence and
cannabis-related problems, changes in risk perception, increases in cannabis
potency, changes in referral practices and increased availability and
accessibility of treatment services.
PMID- 28511184
TI - Are We Overlooking Stroke Chameleons? A Retrospective Study on the Delayed
Recognition of Stroke Patients.
AB - BACKGROUND AND PURPOSE: New effective recanalization therapies are currently
available for acute ischemic stroke; yet a vast majority of stroke patients are
left untreated. The lack of early recognition may be because often times, stroke
patients present with atypical manifestations that resemble other conditions
(which are referred to as "stroke chameleons"). We set to study the proportion of
patients with delayed stroke recognition in a single center. METHODS: We
performed a retrospective analysis of a prospectively collected data over a 9
year period. All adult patients discharged with the diagnosis of ischemic stroke
or transient ischemic attack (TIA) were identified and traced for their diagnosis
on admission. Those cases with a diagnosis other than ischemic stroke or TIA on
admission were identified as possible stroke chameleons and categorized into
different groups according to the occurrence of neurological or non-neurological
manifestations at presentation. RESULTS: Of 2,303 cases with discharge diagnosis
of ischemic stroke or TIA, 919 (39.9%) were found to be possible stroke
chameleons. More than half of these patients (58.4%) presented with neurological
manifestations including disorders of the somatic sensation (33%), alteration of
consciousness (30%), and disorders of speech/language (11%). The remaining
possible stroke chameleons had manifestations pertaining to other organ systems
such as cardiopulmonary, gastrointestinal, systemic infection, trauma, and
thromboembolic events elsewhere. CONCLUSIONS: In our cohort, a surprisingly large
percentage of possible stroke chameleons was observed. It is important to confirm
our findings, study the impact on clinical outcome, and develop strategies for
early stroke patient recognition.
PMID- 28511185
TI - Evaluation of Total, Active, and Specific Myeloperoxidase Levels in Women with
and without Endometriosis.
AB - Myeloperoxidase (MPO) is a proinflammatory enzyme and a marker for neutrophil
activation and oxidative stress. Since oxidative stress and inflammation are
linked to the pathogenesis of endometriosis, we hypothesized that the total,
active, and specific (active/total) MPO levels were significantly different in
plasma of women with and without endometriosis. Samples were selected from our
biobank from women with endometriosis (n = 212) and controls without
endometriosis (n = 121) across the menstrual cycle. Total MPO plasma levels were
measured by immunoassay and MPO activity by enzymatic assay. Total and active MPO
levels did not differ significantly among endometriosis cases and controls,
whereas the specific MPO activity was significantly lower in women with
endometriosis than that in controls (p = 0.0159). After the subdivision of
control patients into women with a normal pelvis and women with other benign
gynecological disorders, a significant difference was observed only between women
with endometriosis and women with other benign gynecological disorders (p =
0.0266). In conclusion, systemic MPO levels may not be suited as a single
biomarker for endometriosis. Our data support the involvement of MPO in other
gynecological disorders but do not provide any evidence for an association with
endometriosis.
PMID- 28511186
TI - Search for Internal Cancers in Mice Tattooed with Inks of High Contents of
Potential Carcinogens: A One-Year Autopsy Study of Red and Black Tattoo Inks
Banned in the Market.
AB - BACKGROUND AND OBJECTIVE: Tattoo ink stock products often contain potential
carcinogens, which on large-scale population exposure may be clinically relevant.
The aim of this autopsy study in mice was to screen major organs for clinical and
subclinical cancers. METHODS: Mice were tattooed on their backs. In total, 48
mice were included and divided into 4 groups; 11 mice tattooed black, 10 tattooed
red, and 5 mice serving as untreated controls. A group of 22 mice with black
tattoos and exposed to ultraviolet radiation (UVR) were also studied. The black
and red inks were both stock products banned on the Danish market due to the
measured contents of potential carcinogens; benzo(a)pyrene and 2-anisidine,
respectively. The mice were housed for 1 year after tattooing, and autopsy study
on internal organs was performed. Tissue samples were systematically taken from
major organs for screening of subclinical changes, not detected by visual
examination. Any observed deviation from normal structure was subject to biopsy
and light microscopy. RESULTS: All mice survived the 1-year observation period.
Autopsy revealed no macroscopic signs of cancer. Microscopic search of internal
organs showed no subclinical or clinical cancer. CONCLUSION: Despite extensive
tattoos with 2 banned inks, the long-term observation in mice showed no internal
cancers nor was the combination of carcinogen and UVR associated with cancer.
Lack of observed malignancy might be explained by the fact that tattooing is only
a single dose exposure. Registered data on carcinogens relies on repeated or
chronic exposures. The study does not support the hypothesis that tattooing
causes cancer.
PMID- 28511188
TI - Calprotectin in Daily Practice: Where Do We Stand in 2017?
AB - BACKGROUND: To make a distinction between organic and functional disease is
essential for gastroenterologists in their daily practice, but it may be
challenging, given the variety and aspecificity of gastrointestinal symptoms
among the general population. The clinician aim is to avoid diagnostic delay and
to restrict unnecessary invasive and expensive exams. SUMMARY: Faecal markers, in
particular faecal calprotectin (FC), have given proof of being reliable markers
of intestinal inflammation with good clinical sensitivity. Calprotectin is useful
in the differential diagnosis between inflammatory bowel disease and irritable
bowel syndrome, as well as in the follow-up of inflammatory bowel disease
patients and in predicting treatment response, with an excellent correlation with
endoscopic activity. Its role in collagenous colitis and infectious colitis is
less clear and still under investigation. Key Message: Despite the growing
evidence supporting its use, many clinicians are uncomfortable in dosing FC, due
to its low specificity and the variability of cut-off values. Indeed there are no
clear guidelines about how to manage patients with intermediate levels of FC. The
aim of this article is to review recent literature on calprotectin and its use.
The strong points and the limits of FC measurement will be analysed, and a
practical approach in the daily clinical routine will be proposed.
PMID- 28511187
TI - The Differential Effects of Erythropoietin Exposure to Oxidative Stress on
Microglia and Astrocytes in vitro.
AB - The neonatal brain is especially susceptible to oxidative stress owing to its
reduced antioxidant capacity. Following hypoxic-ischemic (HI) injury, for
example, there is a prolonged elevation in levels of hydrogen peroxide (H2O2) in
the immature brain compared to the adult brain, resulting in lasting injury that
can lead to life-long disability or morbidity. Erythropoietin (Epo) is one of few
multifaceted treatment options that have been promising enough to trial in the
clinic for both term and preterm brain injury. Despite this, there is a lack of
clear understanding of how Epo modulates glial cell activity following oxidative
injury, specifically, whether it affects microglia (Mg) and astrocytes (Ast)
differently. Using an in vitro approach using primary murine Mg and Ast subjected
to H2O2 injury, we studied the oxidative and inflammatory responses of Mg and Ast
to recombinant murine (rm)Epo treatment. We found that Epo protects Ast from H2O2
injury (p < 0.05) and increases secreted nitric oxide levels in these cells (p <
0.05) while suppressing intracellular reactive oxygen species (p < 0.05) and
superoxide ion (p < 0.05) levels only in Mg. Using a multiplex analysis, we noted
that although H2O2 induced the levels of several chemokines, rmEpo did not have
any significant specific effects on their levels, either with or without the
presence of conditioned medium from injured neurons (NCM). Ultimately, it appears
that rmEpo has pleiotropic effects based on the cell type; it has a protective
effect on Ast but an antioxidative effect only on Mg without any significant
modulation of chemokine and cytokine levels in either cell type. These findings
highlight the importance of considering all cell types when assessing the
benefits and pitfalls of Epo use.
PMID- 28511189
TI - The Role of Audiometry prior to High-Dose Cisplatin in Patients with Head and
Neck Cancer.
AB - OBJECTIVES: To analyze the role of audiometry in considering change to a less
ototoxic treatment in head and neck cancer (HNC) patients. METHODS: Consecutive
patients prescribed high-dose cisplatin (100 mg/m2) between January 2013 and
February 2015 were enrolled. Audiometry was performed at baseline and before
cisplatin. Change to a less ototoxic agent or reduced cisplatin dose was
considered with audiometric decreases >25 dB. RESULTS: A total of 103 patients
were included; the median age of the patients was 59 years (range 18-75).
Cisplatin was intended curative (58%), adjuvant (32%), or palliative (10%). Forty
two participants (41%) did not commence high-dose cisplatin because of baseline
audiometric alterations. Of 61 patients treated with high-dose cisplatin, 40
(66%) showed marked ototoxicity at the end of treatment. The mean hearing loss
between initial and final audiometries showed a hearing loss at 4 and 8 kHz in
both ears (p = 0.002). Thirteen patients switched to carboplatin and 15 to a
lower dose of cisplatin. The outcome was not significantly altered when cisplatin
was replaced with carboplatin or cetuximab. CONCLUSIONS: Audiometric alterations
are common in HNC with high-dose cisplatin, and switching to a less ototoxic
regimen does not adversely affect outcome. Audiometric examination could help to
prevent hearing loss in this population.
PMID- 28511190
TI - Psychotherapy Technique Related to Changes in Anxiety Symptoms With a
Transdiagnostic Sample.
AB - The current study examined how techniques in a psychodynamic model of therapy
(Blagys and Hilsenroth, Clin Psychol Sci Pract. 7, 167-188, 2000) were related to
changes in anxiety symptoms across early treatment process among a
transdiagnostic sample of patients with primary anxiety disorder, subclinical
anxiety disorder, and no anxiety disorder. Secondary analyses examined the use of
specific psychodynamic techniques in relation to symptom change. Results revealed
that therapists' use of psychodynamic-interpersonal (PI) techniques were
significantly and directly related to changes in anxiety symptoms, in line with
previous findings (Pitman, Slavin-Mulford, and Hilsenroth, J Nerv Ment Dis. 202,
391-396, 2014). In addition, patients with co-occurring axis I and II disorders
demonstrated positive changes in anxiety symptoms regardless of level of PI
technique used, whereas patients without co-occurring disorders experienced
greater improvement with more PI. Implications for transdiagnostic treatment
protocols for anxiety, notably Leichsenring and Salzer's (Psychotherapy 51, 224,
2104) Unified Psychodynamic Protocol for Anxiety Disorders, are discussed in
relation to the current findings.
PMID- 28511191
TI - Death by Suicide Within 1 Week of Hospital Discharge: A Retrospective Study of
Root Cause Analysis Reports.
AB - There is a high risk for death by suicide after discharge from an inpatient
mental health unit. To better understand system and organizational factors
associated with postdischarge suicide, we reviewed root cause analysis reports of
suicide within 7 days of discharge from across all Veterans Health Administration
inpatient mental health units between 2002 and 2015. There were 141 reports of
suicide within 7 days of discharge, and a large proportion (43.3%, n = 61)
followed an unplanned discharge. Root causes fell into three major themes
including challenges for clinicians and patients after the established process of
care, awareness and communication of suicide risk, and flaws in the established
process of care. Flaws in the design and execution of processes of care as well
as deficits in communication may contribute to postdischarge suicide. Inpatient
teams should be aware of the potentially heightened risk for suicide among
patients with unplanned discharges.
PMID- 28511192
TI - Individual Variation in Hunger, Energy Intake, and Ghrelin Responses to Acute
Exercise.
AB - PURPOSE: This study aimed to characterize the immediate and extended effect of
acute exercise on hunger, energy intake, and circulating acylated ghrelin
concentrations using a large data set of homogenous experimental trials and to
describe the variation in responses between individuals. METHODS: Data from 17 of
our group's experimental crossover trials were aggregated yielding a total sample
of 192 young, healthy males. In these studies, single bouts of moderate to high
intensity aerobic exercise (69% +/- 5% VO2 peak; mean +/- SD) were completed with
detailed participant assessments occurring during and for several hours
postexercise. Mean hunger ratings were determined during (n = 178) and after (n =
118) exercise from visual analog scales completed at 30-min intervals, whereas ad
libitum energy intake was measured within the first hour after exercise (n = 60)
and at multiple meals (n = 128) during the remainder of trials. Venous
concentrations of acylated ghrelin were determined at strategic time points
during (n = 118) and after (n = 89) exercise. RESULTS: At group level, exercise
transiently suppressed hunger (P < 0.010, Cohen's d = 0.77) but did not affect
energy intake. Acylated ghrelin was suppressed during exercise (P < 0.001,
Cohen's d = 0.10) and remained significantly lower than control (no exercise)
afterward (P < 0.024, Cohen's d = 0.61). Between participants, there were notable
differences in responses; however, a large proportion of this spread lay within
the boundaries of normal variation associated with biological and technical
assessment error. CONCLUSION: In young men, acute exercise suppresses hunger and
circulating acylated ghrelin concentrations with notable diversity between
individuals. Care must be taken to distinguish true interindividual variation
from random differences within normal limits.
PMID- 28511193
TI - A Validation Study of the Fitbit One in Daily Life Using Different Time
Intervals.
AB - PURPOSE: Accelerometer-based wearables can provide the user with real-time
feedback through the device's interface and the mobile platforms. Few studies
have focused on the minute-by-minute validity of wearables, which is essential
for high-quality real-time feedback. This study aims to assess the validity of
the Fitbit One compared with the ActiGraph GT3x + for assessing physical activity
(i.e., steps, time spent in moderate, vigorous, and moderate-vigorous physical
activity) in young adults using traditional time intervals (i.e., days) and
smaller time intervals (i.e., minutes and hours). METHODS: Healthy young adults
(N = 34) wore the ActiGraph GT3x+ and a Fitbit One for 1 wk. Three aggregation
levels were used: minute, hour, and day. Mixed models analyses, intraclass
correlation coefficients, Bland-Altman analyses, and absolute error percentage
for steps per day were conducted to analyze the validity for steps and minutes
spent in moderate, vigorous, and moderate-vigorous physical activity. RESULTS: As
compared with ActiGraph (mean = 9 steps per minute, 509 steps per hour and 7636
steps per day), the Fitbit One systematically overestimated physical activity for
all aggregation levels: on average 0.82 steps per minute, 45 steps per hour, and
677 steps per day. Strong and significant associations were found between
ActiGraph and Fitbit results for steps taken (B = 0.72-0.89). Weaker but
statistically significant associations were found for minutes spent in moderate,
vigorous, and moderate-vigorous physical activity for all time intervals (B =
0.39-0.57). CONCLUSIONS: Although the Fitbit One overestimates the step activity
compared with the ActiGraph, it can be considered a valid device to assess step
activity, including for real-time minute-by-minute self-monitoring. However,
agreement and correlation between ActiGraph and Fitbit One regarding time spent
in moderate, vigorous, and moderate-vigorous physical activity were lower.
PMID- 28511194
TI - Brushing Your Way to Allergic Contact Dermatitis: Anethole Allergy.
PMID- 28511195
TI - Safety Aspects of Postanesthesia Care Unit Discharge without Motor Function
Assessment after Spinal Anesthesia: A Randomized, Multicenter, Semiblinded,
Noninferiority, Controlled Trial.
AB - BACKGROUND: Postanesthesia care unit (PACU) discharge without observation of
lower limb motor function after spinal anesthesia has been suggested to
significantly reduce PACU stay and enhance resource optimization and early
rehabilitation but without enough data to allow clinical recommendations.
METHODS: A multicenter, semiblinded, noninferiority randomized controlled trial
of discharge from the PACU with or without assessment of lower limb motor
function after elective total hip or knee arthroplasty under spinal anesthesia
was undertaken. The primary outcome was frequency of a successful fast-track
course (length of stay 4 days or less and no 30-day readmission). Noninferiority
would be declared if the odds ratio (OR) for a successful fast-track course was
no worse for those patients receiving no motor function assessment versus those
patients receiving motor function assessment by OR = 0.68. RESULTS: A total of
1,359 patients (98.8% follow-up) were available for analysis (93% American
Society of Anesthesiologists class 1 to 2). The primary outcome occurred in 92.2%
and 92.0%, corresponding to no motor function assessment being noninferior to
motor function assessment with OR 0.97 (95% CI, 0.70 to 1.35). Adverse events in
the ward during the first 24 h occurred in 5.8% versus 7.4% with or without motor
function assessment, respectively (OR, 0.77; 95% CI, 0.5 to 1.19, P = 0.24).
CONCLUSIONS: PACU discharge without assessment of lower limb motor function after
spinal anesthesia for total hip or knee arthroplasty was noninferior to motor
function assessment in achieving length of stay 4 days or less or 30-day
readmissions. Because a nonsignificant tendency toward increased adverse events
during the first 24 h in the ward was discovered, further safety data are needed
in patients without assessment of lower limb motor function before PACU
discharge.
PMID- 28511196
TI - To Stop or Not, That Is the Question: Acute Pain Management for the Patient on
Chronic Buprenorphine.
PMID- 28511197
TI - Preclinical Toxicity Screening of Intrathecal Oxytocin in Rats and Dogs: Erratum.
PMID- 28511199
TI - Epidemiology and Risk Factors of Nonalcoholic Fatty Liver Disease Among Patients
with Inflammatory Bowel Disease.
AB - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has been increasingly
identified in patients with inflammatory bowel disease (IBD). We aimed to
determine risk factors of NAFLD in patients with IBD. METHODS: We examined 3
groups of patients: IBD + NAFLD, IBD only, and NAFLD only. Data on demographics,
body mass index, duration of IBD, type of medication use, laboratory data, and
metabolic risk factors were collected. RESULTS: A total of 168 patients between
the ages 19 and 82 were evaluated, 56 patients in each group. Patients with IBD +
NAFLD were significantly older than IBD only patients 45.0 (+/-14.1) versus 35.0
(+/-13), P = 0.007, and their mean body mass index was higher 30.4 (+/-10.2)
versus 25.6 (+/-6.4); P = 0.002. IBD + NAFLD patients in comparison with IBD only
patients had significantly longer duration of IBD (20 [+/-12.2] versus 10 [+/
7.7], P = 0.004), had an increased risk of diabetes (16% versus 2%, P = 0.01),
and obesity (40% versus 20%, P = 0.02). There were no differences in the mean age
or the mean body mass index (32.6 versus 30.4, P = 0.07) between patients with
IBD + NAFLD and NAFLD only. More patients were obese in the NAFLD only group
compared with the IBD + NAFLD group (59% versus 40%, P = 0.03), had hypertension
(55% versus 33%, P = 0.02), hyperlipidemia (53% versus 17.5%, P = 0.0001), and
diabetes (40% versus 16%, P = 0.0001). CONCLUSIONS: IBD patients with NAFLD had
longer disease duration of IBD and developed NAFLD with fewer metabolic risk
factors than patients with NAFLD only. These findings suggest that there may be
other factors that contribute to the development of NAFLD in the IBD population.
PMID- 28511200
TI - Enteric Infection in Relapse of Inflammatory Bowel Disease: The Utility of Stool
Microbial PCR Testing.
AB - BACKGROUND: The similar presentations in relapse of inflammatory bowel disease
(IBD) and enteric infection pose substantial barriers to diagnosis and treatment.
The objective of this study was to investigate the incidence, etiology,
predictors, and treatment of enteric infection in patients with IBD. METHODS: We
reviewed the records of 214 patients with IBD who underwent 295 gastrointestinal
pathogen panel and Clostridium difficile infection (CDI) polymerase chain
reaction (PCR) stool tests during an exacerbation of symptoms. We collected
baseline characteristics, PCR outcomes, and medication exposures. We tested for
associations via the Chi-square test and the t-test. Logistic regression analysis
was used to identify predictors of enteric infection. RESULTS: Of 295 PCR tests
ordered during an exacerbation of symptoms, 38 (12.9%) were positive for CDI and
41 (13.8%) were positive for 14 other pathogens, with E. coli species as the most
common. A previous history of CDI or colonic involvement of IBD predicted CDI,
whereas a previous colectomy predicted negative testing for CDI. The majority
with CDI (24, 63.2%) received oral vancomycin and 15 (37.5%) with other enteric
pathogens were treated for their infection. Patients with CDI had a longer median
length of hospital stay (8.5 versus 4 days, P = 0.041). Patients who tested
negative for enteric infections were more likely to have IBD medications added or
up-titrated (P = 0.027). CONCLUSIONS: Enteric infection was detected in 79
(26.8%) symptomatic patients with IBD , with CDI the most frequent followed by E.
coli. Negative stool PCR testing was associated with changes in IBD management.
Broad enteric PCR testing should be considered during relapse of IBD.
PMID- 28511198
TI - Clinical Utility of Fecal Calprotectin Monitoring in Asymptomatic Patients with
Inflammatory Bowel Disease: A Systematic Review and Practical Guide.
AB - BACKGROUND: In asymptomatic patients with inflammatory bowel disease (IBD),
"monitoring" involves repeated testing aimed at early recognition of disease
exacerbation. We aimed to determine the usefulness of repeated fecal calprotectin
(FC) measurements to predict IBD relapses by a systematic literature review.
METHODS: An electronic search was performed in Medline, Embase, and Cochrane from
inception to April 2016. Inclusion criteria were prospective studies that
followed patients with IBD in remission at baseline and had at least 2
consecutive FC measurements with a test interval of 2 weeks to 6 months.
Methodological assessment was based on the second Quality Assessment of
Diagnostic Accuracy Studies (QUADAS-2) checklist. RESULTS: A total of 1719
articles were identified; 193 were retrieved for full text review. Six studies
met eligibility for inclusion. The time interval between FC tests varied between
1 and 3 months. Asymptomatic patients with IBD who had repeated FC measurements
above the study's cutoff level had a 53% to 83% probability of developing disease
relapse within the next 2 to 3 months. Patients with repeated normal FC values
had a 67% to 94% probability to remain in remission in the next 2 to 3 months.
The ideal FC cutoff for monitoring could not be identified because of the limited
number studies meeting inclusion criteria and heterogeneity between selected
studies. CONCLUSIONS: Two consecutively elevated FC values are highly associated
with disease relapse, indicating a consideration to proactively optimize IBD
therapy plans. More prospective data are necessary to assess whether FC
monitoring improves health outcomes.
PMID- 28511201
TI - ?
PMID- 28511202
TI - [Protective Effects of Muller Glia Cells Towards Retinal Ganglion Cells].
AB - INTRODUCTION: Muller glial cells carry out different tasks to warrant normal
retinal functions. The aim of this study was to investigate if Muller cells also
support retinal ganglion cells (RGC). MATERIALS AND METHODS: RGC were cultured
for 24 hours in the presence or absence of Muller glial cells under normoxic (20%
O2, 5% CO2) or hypoxic (0.2% O2, 5% CO2, 94.8% N2) culture conditions. The number
of vital RGC and the length of the newly developed neurites were evaluated.
RESULTS: Under normoxic conditions, RGC vitality was significantly higher (p <
0.01) when cultured with Muller cells (62.85 +/- 2.06%) than without (47.29 +/-
2.83%). Under hypoxia, RGC vitality was significantly higher (p < 0.01) in co
cultures (41.07 +/- 2.28%) than in homotypic RGC cultures (28.49 +/- 2.16%). The
maximum length of the newly developed neurites was found in the normoxic co
culture (90.7 +/- 7.4 um), but showed only a minor difference (p = 0.04) when
compared to the normoxic homotypic RGC culture. CONCLUSION: Muller glial cells
support RGC under normoxic and hypoxic culture conditions. Length of newly
developed neurites and number of surviving RGC are both parameters to evaluate
cell vitality.
PMID- 28511204
TI - [Current Immunization Status of Dusseldorf's Nursery School Children and Staff
Members: A Cross-Sectional Study].
AB - Background The local health authority (Gesundheitsamt) in Dusseldorf, Germany
aimed to investigate the current immunization status of nursery school children
and pedagogues in Dusseldorf, Germany. Furthermore, analysing the association
between Dusseldorf's 5 social environment clusters and immunization status was of
interest. Especially due to recent changes in the German Infection Protection Act
closely monitoring adverse immunization trends becomes increasingly important.
Methods Weighted cluster random sampling was used in order to draw a sample of 50
nursery schools from the 5 social environment clusters. Questionnaires were sent
to the nursery schools and data were subsequently analysed using descriptive
statistics. Results The results indicate that 76.0% of the children were
immunized in time against MMR, 68.2% against varicella and 75.4% against
meningococcal serogroup C. Data indicated a higher number of immunized children
among older age groups. 96.4% of staff members born after 1970 were not
vaccinated against varicella, 17.9% were not immunized against MMR and 82.1% were
not vaccinated against meningococcal serogroup C. Conclusion Immunization rates
of children in nursery schools in Dusseldorf are far lower compared to local,
federal and nationwide data of children's school entrance health examination.
Especially in nursery schools that care for children younger than 12 months, herd
immunity is crucial. Therefore, administering vaccines with a delay is considered
to be precarious. Due to low response rates, inferential statistics could not be
used and conclusions about the staff members' data are limited.
PMID- 28511203
TI - [Intraindividual Keratoconus Progression].
AB - Introduction Keratoconus is a typically bilateral, progressive-extending corneal
disease. The aim of this work is to evaluate the intraindividual progression of
keratoconus. Patients and Methods This single-center retrospective study of
disease progression based on topographic data from non-operated keratoconus
patients (n = 48) was examined over a period of two years. Seven topographical
keratoconus indices derived from Scheimpflug tomography were used to compare both
the initial findings, as well as the progression of the fellow eyes. Results The
mean observation period was 3.3 +/- 0.9 years. The initial findings illustrated
that a pair of eyes did not correlate with each other (p > 0.05). When comparing
baseline and the progression of the individual indices, a negative correlation
was found for all indices (p < 0.05). Progression and age did correlate for index
smallest radius (Rmin, (R = 0.376, p = 0.008) and index of height decentration
(IHD, R = 0.291, p = 0.045). Regarding the intraindividual progression, we found
a weak correlation to the index of surface variance (ISV, R = - 0.399, p =
0.005), index of vertical asymmetry (IVA, R = - 0.291, p = 0.045) and the
keratoconus index (KI, R = 0.307, p = 0.038). Conclusions The intraindividual
asymmetry, which is typical for keratoconus, could be verified. This study
suggests that the progression of keratoconus in one eye is independent of the
progression in the fellow eye. In this small group of patients, age relationship
to keratoconus could not be demonstrated for all keratoconus indices.
PMID- 28511205
TI - [Stability and Change of Medical Specialty of Residents over Four Years of
Postgraduate Training in Germany].
AB - Aim We analyzed medical residents' preferences in Germany with regard to the
specialization fields after 4 years of postgraduate training and compared them to
their preferences in the years before, e. g. at the end of undergraduate
education in a gender comparative perspective, including the influence of
parenthood. Methods The study is based on annual postal surveys of students of 7
medical faculties in Germany from their last year of medical school ("Practical
Year") until after 4 years of postgraduate training. The return rate at baseline
was 48% and in the 4 surveys thereafter the rates were 85% and above. In all
samples, about two-thirds of respondents were women, which corresponds to the
actual gender distribution in under- and postgraduate training. Descriptive
statistics and regression analyses were used. Results Compared to the end of
undergraduate education, anaesthesiology and general practice were the
disciplines which gained in attraction, whereas surgical disciplines lost
significantly in their attraction. These developments were similar in both
genders. Specialized internal medicine, paediatrics and gynaecology lost
attraction among female physicians only. We found important correlations of
disciplinary preferences with parenthood and with the preference for part-time
work after graduation. Conclusion The data show that "feminization" is not the
reason why both anaesthesiology and general practice gained in attraction, since
this happened over the 4 years among both male and female physicians. The loss in
attraction in all great clinical disciplines, especially in surgery, orthopaedics
and urology, may lead to severe problems in supply of medical manpower in the
hospital, especially when combined with preference for part-time work.
PMID- 28511207
TI - ?
PMID- 28511208
TI - ?
PMID- 28511206
TI - ?
AB - In the recent study by Verhoeven and Egger, 2015 and the recent letter to the
editor by Boot et al. 2015 an emphasis is given to the best possible
pharmacological treatment of 22q11-2 Deletion-Syndrome related psychoses. We
would like to present the case of a 23-year old Cypriot patient with 22q11.2
deletion syndrome who fulfilled criteria for treatment resistant schizophrenia
(TRS). He was sequentially treated with aripiprazole, risperidone, olanzapine,
haloperidol and a combination treatment with olanzapine and haloperidol.
Clozapine was the only antipsychotic medication that has improved his condition.
PMID- 28511209
TI - ?
PMID- 28511210
TI - ?
PMID- 28511211
TI - ?
PMID- 28511212
TI - ?
PMID- 28511213
TI - ?
PMID- 28511214
TI - ?
PMID- 28511216
TI - ?
PMID- 28511215
TI - ?
PMID- 28511217
TI - ?
PMID- 28511218
TI - ?
PMID- 28511219
TI - [Innovative Ultrasound: Contrast-Enhanced Ultrasound of the Kidneys].
AB - Ultrasound examination of the kidneys with grey-scale imaging and colour Doppler
ultrasound is the most common renal imaging modality. A few years ago, contrast
enhanced ultrasound (CEUS) emerged as a non-invasive perfusion imaging modality
to evaluate the renal vessels and microvascularisation. These contrast media
contain intravenous microbubbles (sulfur hexafluoride), which have no deleterious
effect on renal function. Being free of iodine, they also pose no risk for the
thyroid gland. CEUS of the kidneys is mainly used for the evaluation of renal
cysts and the analysis of renal lesions suspicious for malignancy. Also this
method is used to visualise inflammation as well as renal perfusion after trauma
or infarction.
PMID- 28511220
TI - [Significance and Value of PSMA Ligands in Prostate Cancer].
AB - In recent years, PSMA-targeting PET tracers such as 68Ga-PSMA-11 have shown
promising results, thus contributing to a better management of prostate cancer
patients. At the present time, 68Ga-PSMA-11 is most frequently used for
diagnostic evaluation in the setting of biochemical recurrence of prostate
cancer. In this context, the 68Ga-PSMA-11 PET/CT delivers superior detection
rates compared to conventional imaging, especially for the detection of small,
unsuspicious lesions or lesions in the presence of low PSA values. Furthermore,
68Ga-PSMA PET imaging seems to be an encouraging alternative for the staging of
high-risk patients, particularly in combination with multiparametric MRI. In
addition to the increasing use of PSMA ligands in clinical diagnostics, some
variants have also been successfully applied in therapy. Advanced metastasized
prostate cancer patients showed a good response to PSMA radioligand therapy with
tolerable side-effects after failure of guideline-compliant treatment.Due to
recent developments, PSMA ligands will continue to play an important role in the
management of prostate cancer patients and will be more widely used in the
future.
PMID- 28511221
TI - [PSMA-Radioguided Surgery for Salvage Lymphadenectomy in Recurrent Prostate
Cancer].
AB - Recently, the use of 111In-labeled PSMA-I&T-based radioguided surgery (111In-PSMA
RGS) for salvage surgery using intraoperative ex-vivo gamma-probe measurements
has been described by our group as a promising new and individual treatment
concept in patients with localised recurrent prostate cancer (PC). 111In-PSMA-RGS
allowed for the intraoperative identification of metastatic lesions with a
sensitivity, specificity and accuracy of 92.3, 93.5 and 93.1%, respectively,
compared to histopathology. 111In-PSMA-RGS was able to detect 5 additional lymph
node metastases in 3 out of 31 patients compared to 68Ga-HBED-CC-PSMA PET. A PSA
decline >50 and >90% was observed in 24/31 patients and 17/31 patients,
respectively. In 19/31 patients even a complete biochemical response was
observed. 10/31 patients received further PC-specific treatment after a median of
125 days following 111In-PSMA-RGS. Surgery-related complications were observed in
10 patients (Clavien-Dindo classification: grade 1 n=6, grade 3b n=4). 111In-PSMA
RGS seems to be highly valuable for the intraoperative detection of small
metastatic lesions in PC patients scheduled for salvage lymphadenectomy. It
allows for an exact localisation and resection of metastatic tissue during 111In
PSMA-RGS and thus is anticipated to have a beneficial influence on further
disease progression. However, the identification of suitable patients on the
basis of 68Ga-PSMA PET imaging and clinical parameters is critical to obtain
satisfactory results.
PMID- 28511223
TI - ?
PMID- 28511222
TI - Cellular Angiofibroma of the Spermatic Cord.
AB - Cellular angiofibromas are rare, slow-growing mesenchymal tumours, most often
localised in the vulva and perineum of women. We present a case of a 60-year-old
male with a 7-cm large cellular angiofibroma in the inguinal canal extending
toward the testis, detected after inguinal herniorraphy. Inguinal orchiectomy was
performed and the pathology report revealed a cellular angiofibroma containing a
lot of mast cells in the stroma, which was collagenised with spindle-shaped cells
and characterised by hyalinised vascular structures. The localisation and nature
of this type of mass makes initial diagnosis difficult. Differential diagnosis is
important to rule out histologically malignant aggressive angiomyxomas and other
solitary fibrous tumours. As local recurrence may occur after resection, long
term follow-up is necessary.
PMID- 28511224
TI - ?
PMID- 28511225
TI - Comment on The 100 Most-Cited Articles Focused on Ultrasound Imaging: A
Bibliometric Analysis.
PMID- 28511226
TI - Contrast-Enhanced Ultrasound in the Follow-Up of Endoleaks after Endovascular
Aortic Repair (EVAR).
AB - Endovascular aortic repair (EVAR) has become established in the treatment of
abdominal aortic aneurysms and shows potential benefits such as a low
perioperative morbidity and a short hospitalization duration. The follow-up after
EVAR primarily consists of lifelong postinterventional imaging of the aneurysm
size in order to detect complications such as endoleaks or stent dislocation.
Computed tomography angiography, an imaging modality that uses ionizing radiation
and that relies on a contrast medium which is dependent on thyroid and renal
function, is widely used for follow-up. Meanwhile, contrast-enhanced ultrasound
(CEUS) has been established as a viable, fast and cost-effective imaging
alternative for the follow-up and the detection of endoleaks after EVAR with the
additional benefit of being a real-time non-ionizing radiation examination and
having comparable or even superior diagnostic performance. This review describes
the use of CEUS for follow-up after EVAR and describes the most common
pathologies.
PMID- 28511227
TI - Tenosynovitis Evaluation Using Image Fusion and B-Flow - A Pilot Study on New
Imaging Techniques in Rheumatoid Arthritis Patients.
AB - Aim The aim of this study was to compare the assessment of tenosynovitis by
ultrasound (US) and magnetic resonance imaging (MRI) using the image fusion
technique and to investigate whether US B-flow imaging (BFI) is an alternative to
Doppler US when assessing tenosynovitis. Materials and Methods 15 patients with
rheumatoid arthritis (RA) had US-verified tenosynovitis in the wrist/hand. An MRI
was performed of the wrist/hand with subsequent repeated US and image fusion.
Images were compared in three steps: 1. Visual image comparison, 2. Quantitative
measurement of transverse areas of the affected tendon and tendon sheath, using
two tendon measures on MRI, area 1 and area 2, excluding and including partial
volume artifacts, respectively, 3. Assessment using the OMERACT semi-quantitative
scoring systems for US and MRI. Furthermore, BFI was assessed as: 0: No flow, 1:
Focal flow, 2: Multifocal flow, 3: Diffuse flow, in the tendon sheath. Results
The median areas on US and MRI (areas 1 and 2) were 0.16 cm2 (25;75 pctl: 0.10;
0.25), 0.9 cm2 (0.06; 0.18) and 0.13 cm2 (0.10; 0.25), respectively, for included
tendons and 0.18 cm2 (0.13; 0.26), 0.27 cm2 (0.20; 0.45) and 0.23 cm2 (0.16;
0.40) for tendon sheaths. No statistically significant difference was found
between US tendon area and MRI tendon area 2 (Wilcoxon's test; p = 0.47).
Overall, the agreement between grayscale and color Doppler (CD) US and MRI
tenosynovitis visualization and scoring was good, but not between CD and BFI.
Conclusion US and MRI have high agreement using image fusion for the assessment
of tenosynovitis when partial volume artifacts are taken into account. BFI is not
an alternative to CD for the measurement of slow flow in tenosynovitis.
PMID- 28511228
TI - The 100 Most-Cited Articles Focused on Ultrasound Imaging: A Bibliometric
Analysis.
AB - Purpose The number of citations that an article has received reflects its impact
on a particular research area. The aim of this study was to identify the 100 most
cited articles focused on ultrasound (US) imaging and to analyze the
characteristics of these articles. Methods We determined the 100 most-cited
articles on US imaging via the Web of Science database, using the search term.
The following parameters were used to analyze the characteristics of the 100 most
cited articles: publication year, journal, journal impact factor, number of
citations and annual citations, authors, department, institution, country, type
of article, and topic. Results The number of citations for the 100 most-cited
articles ranged from 1849 to 341 (median: 442.0) and the number of annual
citations ranged from 108.0 to 8.1 (median: 22.1). The majority of articles were
published in 1990 - 1999 (39 %), published in radiology journals (20 %),
originated in the United States (45 %), were clinical observation studies (67 %),
and dealt with the vessels (35 %). The Department of Internal Medicine at the
University of California and the Research Institute of Public Health at the
University of Kuopio (n = 4 each) were the leading institutions and Salonen JT
and Salonen R (n = 4 each) were the most prolific authors. Conclusion Our study
presents a detailed list and analysis of the 100 most-cited US articles, which
provides a unique insight into the historical development in this field.
PMID- 28511230
TI - [Papillary cystadenoma: a rare differential diagnosis of a paratesticular
tumour].
AB - Testicular and paratesticular cystadenomas arise from an oviduct-like structure,
which, morphologically, is almost identical with the ovarian surface epithelium.
These are very rare benign tumours of adults. They present as asymptomatic cystic
lesions. Bilateral paratesticular cystadenomas are associated with the Von-Hippel
Lindau syndrome and may be associated with infertility. Most cystadenomas are
benign, but a few cases of malignant transformation of embryonic remnants have
been reported in the appendix testis, including cases of adenocarcinoma,
cystadenocarcinoma, and a Mullerian-type epithelial tumour with a low malignant
potential. We report the case of a 74-year-old man with a rare paratesticular
cystadenoma of the male adnexa.
PMID- 28511232
TI - [Priapism in children and adolescents].
AB - Priapism is a prolonged erection without sexual stimulation. In most cases it
requires prompt management in order to avoid long-term consequences such as
erectile dysfunction or penile deformity. Priapism is rare in children, but
haematological diseases play an important role. The diagnosis is generally not
difficult. Blood gas analysis and Doppler sonography are used to establish the
form of priapism and determine its further management. The management of low-flow
priapism consists of immediate blood aspiration and intracavernosal injection of
sympathomimetic drugs as needed. In case of treatment failure, a shunt is also
necessary. High-flow priapism generally does not require any immediate treatment.
X-ray-assisted selective embolisation in case of fistula is associated with a
high success rate. The primary aim in stuttering priapism is reduction and
prophylaxis of erections and patient education about the disease. Penile
prostheses are not used in children.
PMID- 28511229
TI - HPLC-Based Activity Profiling for GABAA Receptor Modulators in Searsia pyroides
Using a Larval Zebrafish Locomotor Assay.
AB - A dichloromethane extract from leaves of Searsia pyroides potentiated gamma
aminobutyric acid-induced chloride currents by 171.8 +/- 54% when tested at 100
ug/mL in Xenopus oocytes transiently expressing gamma aminobutyric acid type A
receptors composed of alpha1beta2gamma2s subunits. In zebrafish larvae, the
extract significantly lowered pentylenetetrazol-provoked locomotion when tested
at 4 ug/mL. Active compounds of the extract were tracked with the aid of HPLC
based activity profiling utilizing a previously validated zebrafish larval
locomotor activity assay. From two active HPLC fractions, compounds 1 - 3 were
isolated. Structurally related compounds 4 - 6 were purified from a later eluting
inactive HPLC fraction. With the aid of 1H and 13C NMR and high-resolution mass
spectrometry, compounds 1 - 6 were identified as analogues of anacardic acid.
Compounds 1 - 3 led to a concentration-dependent decrease of pentylenetetrazol
provoked locomotion in the zebrafish larvae model, while 4 - 6 were inactive.
Compounds 1 - 3 enhanced gamma aminobutyric acid-induced chloride currents in
Xenopus oocytes in a concentration-dependent manner, while 4 - 6 only showed
marginal enhancements of gamma aminobutyric acid-induced chloride currents.
Compounds 2, 3, and 5 have not been reported previously.
PMID- 28511231
TI - [Epididymitis in Children: Fact or Fiction].
AB - Epididymitis is one of the most frequent causes of acute scrotum during
childhood. Unlike in adults, ascending bacterial infections are rarely the
underlying cause of the condition in children. Antibacterial treatment in
accordance with a prior antibiogram is possible in the presence of leukocyturia
and significant bacteriuria. For the remaining cases, there are no definite
criteria allowing for a decision on acute antibacterial treatment. The fact that
antibacterial treatment is still initiated in cases of epididymitis in the
clinical routine setting is based on the assumption of a possible infection
rather than being based on facts. This dilemma will probably not be entirely
resolved until adequate diagnostic markers for the different trigger mechanisms
of epididymitis have been found.
PMID- 28511233
TI - [Diagnostic Imaging in Cases of Acute Scrotum].
AB - Acute scrotum is one of the most common urologic emergencies in children and
adolescents. This condition involves acute testicular pain, which is often
accompanied by scrotal swelling and erythema. It is most important to distinguish
between cases that require immediate surgery and those that can be treated
conservatively. As patient history and physical findings may not always be
unequivocal, ultrasound with Colour-Coded Doppler Sonography is the imaging
modality of choice for further evaluation. Testicular torsion and other
differential diagnoses such as epididymitis, appendiceal torsion, intratesticular
haematoma after trauma, or complicated inguinal hernia have to be considered.
Other imaging modalities such as MRI, scintigraphy and contrast-enhanced
ultrasound are only necessary if the diagnosis remains unclear or if
complications occur during the course of disease.
PMID- 28511234
TI - Indications, results, and clinical impact of endoscopic ultrasound (EUS)-guided
sampling in gastroenterology: European Society of Gastrointestinal Endoscopy
(ESGE) Clinical Guideline - Updated January 2017.
AB - For pancreatic solid lesions, ESGE recommends performing endoscopic ultrasound
(EUS)-guided sampling as first-line procedure when a pathological diagnosis is
required. Alternatively, percutaneous sampling may be considered in metastatic
disease.Strong recommendation, moderate quality evidence.In the case of negative
or inconclusive results and a high degree of suspicion of malignant disease, ESGE
suggests re-evaluating the pathology slides, repeating EUS-guided sampling, or
surgery.Weak recommendation, low quality evidence.In patients with chronic
pancreatitis associated with a pancreatic mass, EUS-guided sampling results that
do not confirm cancer should be interpreted with caution.Strong recommendation,
low quality evidence.For pancreatic cystic lesions (PCLs), ESGE recommends EUS
guided sampling for biochemical analyses plus cytopathological examination if a
precise diagnosis may change patient management, except for lesions <= 10 mm in
diameter with no high risk stigmata. If the volume of PCL aspirate is small, it
is recommended that carcinoembryonic antigen (CEA) level determination be done as
the first analysis.Strong recommendation, low quality evidence.For esophageal
cancer, ESGE suggests performing EUS-guided sampling for the assessment of
regional lymph nodes (LNs) in T1 (and, depending on local treatment policy, T2)
adenocarcinoma and of lesions suspicious for metastasis such as distant LNs, left
liver lobe lesions, and suspected peritoneal carcinomatosis.Weak recommendation,
low quality evidence.For lymphadenopathy of unknown origin, ESGE recommends
performing EUS-guided (or alternatively endobronchial ultrasound [EBUS]-guided)
sampling if the pathological result is likely to affect patient management and no
superficial lymphadenopathy is easily accessible.Strong recommendation, moderate
quality evidence.In the case of solid liver masses suspicious for metastasis,
ESGE suggests performing EUS-guided sampling if the pathological result is likely
to affect patient management, and (i) the lesion is poorly accessible/not
detected at percutaneous imaging, or (ii) a sample obtained via the percutaneous
route repeatedly yielded an inconclusive result.Weak recommendation, low quality
evidence.
PMID- 28511235
TI - Direct peroral cholangioscopy with a new anchoring technique using the guide
probe of Kautz - first clinical experiences.
AB - Background and study aims We present the first clinical results of a new tandem
technique for direct peroral cholangioscopy using a standard ultraslim upper
gastrointestinal endoscope and a guide probe that was originally developed for
the non-transendoscopic placement of biliary endoprostheses (guide probe of
Kautz; MTW, Wesel, Germany). Patients and methods Twenty direct peroral
cholangioscopy procedures were performed with the new anchor-assisted method
using the guide probe of Kautz in a single center and were retrospectively
analyzed. Results Indications for anchor-assisted cholangioscopy procedures
included indeterminate bile duct strictures (n = 14), filling defects that
remained after stone extraction (n = 4), and complex stone extractions (n = 2).
Biliary access and visualization of the target region were achieved in 18/20
procedures (90 %). The interventional success rate was 85 % (11 /13
interventions). One case of postinterventional cholangitis occurred (5 %), along
with one case of minor peri-interventional papillary bleeding (5 %). Conclusions
The anchor-assisted cholangioscopy technique is feasible and safe for direct
cholangioscopy and provides reliable success rates in clinical practice. This
technique represents an alternative approach for direct cholangioscopy on a
single-operator basis using standard endoscopes.
PMID- 28511236
TI - Long-term outcomes after endoscopic ultrasound-guided ablation of pancreatic
cysts.
AB - Background and study aims The aim of this study was to investigate the long-term
outcomes after endoscopic ultrasound (EUS)-guided pancreatic cyst ablation.
Patients and methods In a single-center, prospective study, 164 patients with
pancreatic cysts underwent EUS-guided cyst ablation using ethanol with
paclitaxel. The inclusion criteria were as follows: unilocular or oligolocular
cysts; clinically indeterminate cysts that required EUS fine-needle aspiration;
and/or cysts that grew during the observation period. Treatment response was
classified as complete resolution, partial resolution, or persistent cyst, with <
5 %, 5 % - 25 %, and 25 % of the original cyst volume, respectively. Results The
median largest diameter of the cyst was 32 mm and the median volume was 17.1 mL.
Based on cyst fluid analysis there were 71 mucinous cystic neoplasms, 16 serous
cystic neoplasms, 11 intraductal papillary mucinous neoplasms, 3 pseudocysts, and
63 indeterminate cysts. Sixteen treated patients (9.8 %) had adverse events (1
severe, 4 moderate, and 11 mild). Treatment response was as follows: complete
resolution in 114 (72.2 %), partial resolution in 31 (19.6 %), and persistent
cysts in 13 (8.2 %). Twelve of the 13 patients with persistent cysts underwent
surgery. During clinical and imaging follow-up (median 72 months, interquartile
range 50 - 85 months) of the 114 patients with complete resolution, only two
patients (1.7 %) showed cyst recurrence. Based on multivariate analysis, the
absence of septa (odds ratio [OR] 7.12, 95 % confidence interval [CI] 2.72 -
18.67) and cyst size less than 35 mm (OR 2.39, 95 %CI 1.11 - 5.16) predicted
complete resolution. Conclusion Among patients with pancreatic cysts in whom
complete resolution was achieved after EUS-guided cyst ablation, 98.3 % remained
in remission at 6-year follow-up. Unilocular form and small cyst size were
predictive of complete resolution. This treatment approach may be an effective
and durable alternative to surgery.Trial registered at ClinicalTrials.gov (NCT
00689715).
PMID- 28511237
TI - Performance of a fully disposable, digital, single-operator
cholangiopancreatoscope.
AB - Background and study aim Our aim was to evaluate the first use in humans of a
new, single-use, digital, single-operator intraductal cholangiopancreatoscopy
system (IDCP). Patients and methods Data were collected retrospectively from four
US institutions between February 2015 and April 2015. The visual impression of
neoplasia or benign findings with IDCP was determined by the performing
endoscopist. High grade dysplasia, intraductal papillary mucinous neoplasm,
neuroendocrine tumor, and malignancy were categorized as neoplasia. Benign
disease was defined as the absence of neoplasia during >= 6 months of follow-up.
Results Patients (n = 108) with indeterminate strictures, dilatation, or
difficult stones underwent IDCP. Of 74 patients with indeterminate stricture or
dilatation, 29 (39 %) had neoplasia, of which 25 were confirmed by miniature
biopsy forceps, 2 by surgical pathology, and 2 by the presence of metastatic
disease on follow-up imaging. In patients with benign disease, 15 had concentric
stenosis or normal/erythematous changes, 5 had low papillary mucosal projections,
6 had coarse granular mucosa, and 4 had nodular mucosa. Findings in patients with
neoplastic disease included dilated, tortuous vessels ("tumor vessels"; n = 13),
irregular margins with partial occlusion of the lumen (infiltrative stricture, n
= 12), villous or nodular mass (n = 9), and finger-like villiform projections (n
= 5). Operating characteristics for indeterminate stricture or dilatation were:
97 % sensitivity, 93 % specificity, 90 % positive predictive value, 98 % negative
predictive value. Targeted biopsy yielded 86 % sensitivity and 100 % specificity.
Stone clearance was noted in all cases. Adverse events occurred in 3 %.
Conclusion The new IDCP system provides enhanced image resolution, and may
improve the ability to target difficult stones and diagnose indeterminate
strictures.
PMID- 28511238
TI - [Subjective Adverse Effects during Outpatient CBT: Associations to Patient and
Therapist Variables and to the Therapeutic Alliance].
AB - Background Empirical data on variety, frequency, and prerequisites for unwanted
side effects of psychotherapies are important regarding the planning,
realization, and quality assurance of treatment. The study describes adverse
effects of outpatient psychotherapy treatment and their association with patient,
therapist and treatment characteristics. Methods To reduce memory bias, 70
outpatient psychotherapy patients fulfilled the Inventory for the Assessment of
Negative Effects of Psychotherapy (INEP). Data on patients' characteristics (sex,
age, impairment), therapists' sex, and therpeutic alliance were collected.
Results 84 % percent of patients reported at least one unwanted side effect
(range 1-13; m=3.4; sd=3.43). Patients, age, number and kind of pretreatments,
and the quality of the therapeutic alliance were associated with the frequency of
unwanted negative effects. Discussion Unwanted side effects during outpatient
psychotherapy are common phenomena and need careful attention in patient
education and during the treatment itself.
PMID- 28511239
TI - [Importance of Work and Employment in the Treatment of People with Mental Illness
- Results of a Qualitative Study].
AB - Exclusion of individuals with mental disorders is common, especially exclusion
from the work force. This paper investigates the role of work and the
reintegration into the workforce of patients with mental illness from the mental
health professional's perspective. Within a qualitative study design, 44 mental
health professionals from different settings and regions in Germany were
interviewed. The material was transcribed verbatim and a content analysis was
conducted. It can be shown that work and inclusion in the workforce is an
important topic and that occupational status is discussed early in the treatment
process. However, the roles of mental health professionals in different settings
vary considerably. Within treatment settings, specific concepts and structured
cooperation facilitating the reintegration of patients with mental illness into
the workforce are largely lacking.
PMID- 28511240
TI - [Treatment Outcome in Female In-Patients with Anorexia nervosa and Comorbid
Personality Disorders Prevalence - Therapy Drop out and Weight Gain].
AB - Introduction Personality disorders (PD) are among the most common comorbid
disorders in female patients with Anorexia Nervosa (AN). Recent research findings
suggest that comorbid PD are associated with a higher treatment drop-out rate and
a worse therapeutic outcome. However, no study to date has distinguished between
certain age groups concerning these issues. Research questions Therefore, the
present study focuses on the prevalence of PD (1), treatment drop-out rates (2)
and weight gain (3) in female in-patients with AN. Thereby, we differentiate
among three age groups (17-24 years; 25-34 years; 35-65 years). Material &
Methods We assessed female in-patients (N=331) with AN at the Helios Clinic in
Bad Gronenbach in Germany using the Eating Disorders Inventory-2 and the
psychotherapeutic-medical basic documentation at the beginning and at the end of
their treatment. Furthermore, we investigated the drop-out rate and weight gain
by comparing anorexic patients with and without comorbid PD that were diagnosed
by clinicians using ICD-10 criteria. Results In sum, our patients with AN
demonstrated a prevalence rate of 34% for one or more comorbid PD. Interestingly,
patients between 17-24 years showed a lower prevalence rate of 22% compared to
those between 25-34 years (42%) and 35-65 years (41%). Furthermore, younger age
and comorbid PD seemed to be significant predictors for treatment dropout. One of
the most striking results was that younger patients (17-24) without a comorbid PD
had the highest weight gain during treatment. This could not be observed in
patients with a comorbid PD, who demonstrated the highest weight gain between 25
and 34 years of age. Conclusion Our findings support the hypothesis that comorbid
PD are related to a worse outcome in patients with eating disorders. Future
studies might do well in assessing dimensional scores of personality disorders
and other relevant aspects like for example the amount of social support to draw
further conclusions on these associations. Our results emphasize the need for
more disorder-specific interventions tailoring at patients with AN and comorbid
PD to improve treatment outcome.
PMID- 28511241
TI - [Short- and Mid-Term Effectiveness of Primary and Secondary Prevention of
Comorbid Depressive Symptoms among Patients with Chronic Low Back Pain].
AB - Background Because of high rates of comorbid mental disorders among patients with
chronic low back pain, an intervention for pain competence and depression
prevention for multidisciplinary inpatient rehabilitation was newly developed and
evaluated concerning depressive symptoms, anxiety and pain related parameters.
Methods Per protocol regression analyses with data of n=723 patients were
conducted to evaluate the intervention. Intraindividual changes were quantified
by Cohen's d based on repeated measures analyses of variance. The results of the
regression analyses were validated by n=1306 multiple imputed data. Results
Patients benefited in all analyzed parameters in the short- and mid-term (6
months after intervention) from the rehabilitation with as well as without
supplemental depression prevention training. Depressive symptoms in the beginning
of the rehabilitation were a significant predictor for all analyzed parameters.
Additionally, the depression prevention training reduced the lowest pain
intensity in the short-term independent from depressive symptoms. The results
were confirmed by analyses with multiple imputations. However, improvements
declined especially in depressive symptoms and anxiety in the months after
rehabilitation. Discussion The results support the influence of depressive
symptoms on psychological and pain related parameters, which emphasizes the
relevance of an early treatment of depressive symptoms. Though, the supplemental
depression prevention training had no additional effect in the inpatient
rehabilitation setting, which could be explained by the high effect sizes of the
sole pain competence training. Moreover, beneficial effects should be supported
by aftercare, because effects declined during the 6 months after rehabilitation.
PMID- 28511242
TI - [Depression and Comorbid Personality Disorder - Effectiveness of Psychodynamic
Inpatient Psychotherapy].
AB - Objectives Depression is one of the most common illnesses. The effectiveness of
psychodynamic psychotherapy on depressive symptom load has been demonstrated.
However, for patients suffering from comorbid personality disorder (PD) a
decreased benefit has been reported, as well as fewer rates of remission and
extended duration of remission. However, findings are inconsistent. The objective
of this study was to determine potential differences in therapy-outcome comparing
female patients with and without comorbid PD. Method Including female inpatients
aged between 25-45 years (N=377) in a psychodynamic treatment, the dissenting
outcome on depressive symptom load (among others BDI; HAMD) as well as
psychodynamic variables (IPO) by patients with and without comorbid PD were
analysed within a naturalistic multicenter intervention study (STOP-D). Data were
collected in 15 psychodynamically oriented psychosomatic hospital units in
Germany, based on self- and external-assessment instruments. Results Under
comparable therapy-doses, female patients with and without comorbid PD benefit
significantly from psychodynamic inpatient treatment. By equivalent baseline
severity of clinical symptoms patients without comorbid PD show larger effect
sizes in all inventories than patients with comorbid PD. Discussion Although the
benefit is lower for depressed patients with comorbid personality disorder, the
positive effect of inpatient psychodynamic psychotherapy is statistically and
clinically significant in both groups. Influences of further comorbid symptoms
and confounding symptoms between depression and PD, which were difficult to
control, are possible. Further studies are necessary. Conclusion Although
patients with comorbid PD benefit significantly from the inpatient treatment, a
special therapeutic design seems to be indicated for these patients.
PMID- 28511243
TI - [Emotional Arousal (Voice Stress) and Posttraumatic Growth as well as
Relationship Satisfaction of Partners of Women with Breast Cancer in the Context
of Social Support].
AB - Introduction Breast cancer is associated with significant psychosocial strains
for both patients and partners. Constructive social support and positive
communication behavior have been shown to be protective against the burdens
associated with breast cancer. Individual levels of emotional arousal during
social support interactions with one's spouse are an important aspect of couples'
support behaviors and can be assessed via vocal fundamental frequency (f0).
Methods N=44 couples had standardized seven-minute long interactions asking the
male partner to describe his thoughts and feelings with regard to their wives'
breast cancer. Using actor-partner interdependence models (APIM), f0's
associations with individual posttraumatic growth (PTG) and perceived marital
quality were differentially investigated. Results Significant actor effects for
f0 and PTG were found for both husbands as well as tendencies for partner effects
and wives. Perceived marital quality was not significantly associated with one's
own levels of emotional arousal. No significant partner effects emerged for any
of the variables of interest. Discussion Contrary to findings in couples'
conflict discussions, higher levels of emotional arousal in social support
interactions are associated with positive aspects of psychological functioning.
F0 during social support could be associated with higher levels of self-efficacy,
which might be beneficial for PTG and constructive ways of emotional expression.
Constructive expression of emotional arousal could lead to heightened involvement
in support interactions and may be voiced via higher levels of f0. Further
analyses to replicate these findings are necessary.
PMID- 28511244
TI - Survival and Long-Term Outcomes of Aortic Valve Replacement in Patients Aged 55
to 65 Years.
AB - BACKGROUND: This study aims to compare the outcomes after aortic valve
replacement (AVR) with mechanical and biological valves in middle-aged patients
(55-65 years) to determine the impact on long-term mortality and morbidity.
METHODS: A retrospective analysis of 373 patients between 55 and 65 years of age
who received a primary AVR with or without concomitant coronary artery bypass
graft between April 1995 and March 2014. Propensity matching yielded 118 patient
pairs in the mechanical and biological valve cohorts. RESULTS: Median follow-up
time was 6.9 years. No differences in long-term survival or a composite outcome
of stroke, bleeding, and endocarditis (major adverse prosthesis-related event;
MAPE) were observed in patients receiving biological versus mechanical valves.
Actuarial 15-year survival was 46.4% (95% confidence interval [CI], 28.8-62.3%)
in the biological valve group versus 60.6% (95% CI, 47.5-71.4%) in the mechanical
valve group (hazard ratio, 1.16 [95%CI, 0.69-1.94], p = 0.58). The 15-year
cumulative incidence of MAPE was 53.3% (95% CI, 33.7-69.4%) for biological valves
versus 24.5% (95% CI, 16.2-33.8%) for mechanical valves (hazard ratio, 0.65 [95%
CI, 0.37-1.14], p = 0.12). The 15-year cumulative incidence of reoperation was
higher in the bioprosthetic group (26.0% [95% CI, 14.0-39.8%] vs. 5.4% [95% CI,
2.0-11.4%]; hazard ratio 0.24 [95% CI, 0.09-0.68] p < 0.01). CONCLUSION: There is
no difference in survival and MAPE at 15 years between biological and mechanical
valves. The risk of reoperation was significantly higher in the biological valve
group and may affect valve choice in middle-aged patients.
PMID- 28511245
TI - Low Fibrinogen Is Associated with Increased Bleeding-Related Re-exploration after
Cardiac Surgery.
PMID- 28511246
TI - Early Postoperative Endoscopy for Evaluation of the Anastomosis after Esophageal
Reconstruction.
AB - BACKGROUND: Anastomotic leaks significantly affect hospital stay after esophageal
surgery. Here, we investigated the efficacy of early endoscopy for predicting
anastomotic healing and leaks after esophageal reconstruction. METHODS: A total
of 65 consecutive esophageal cancer patients treated by cervical
esophagogastrostomy underwent routine endoscopy between postoperative days 5 and
7. The anastomosis was scored for the degree of ischemia, stenosis, and torsion
of the anastomotic axis. Independent associations between ischemia, stenosis, and
torsion of the proximal esophagus and the risk of the anastomotic leak were
examined using Spearman's rank correlation method. RESULTS: Assessment of the
degree of mucosal ischemia in 65 patients shows well healing in 35, patch
ischemia in 20, diffuse ischemia in 10, no necrosis in any patient. Stenosis was
classified as 0 to 10% in 40 patients, 11 to 20% in 12, 21 to 80% in 11, and 81
to 100% in 2. The degree of torsion of the anastomotic axis was classified as 0
to 10 degrees in 52 patients, 11 to 90 degrees in 8, and 91 to 180 degrees in 5.
With rising endoscopy scores, there was an increase in risk for leaks (score >
4.5, sensitivity 100%, and specificity 83.8%). CONCLUSIONS: Early postoperative
endoscopy facilitates the management of esophagogastrostomy anastomosis to
predict leaks.
PMID- 28511248
TI - The Importance of Facts and the Role of Academic Publishers in Today's World-A
Publisher's View.
PMID- 28511247
TI - Cardiac Surgeons after Vacation: Refreshed or Rusty?
AB - Introduction: Many surgeons describe feeling a bit out of practice when they
returnfrom a vacation. There have been no studies assessing the impact of surgeon
vacationon patient outcomes. Methods: We used administrative data from the
province of Ontario to identifypatients who underwent a coronary artery bypass
grafting. Using a propensity score,we matched patients who underwent their
procedure immediately after their surgeonreturned from vacation of at least 7
days (n = 1,161) to patients who were notoperated immediately before or after a
vacation period (n = 2,138). Results: There was no significant difference in
patient mortality (odds ratio: 1.23,p = 0.52), length of operation (relative risk
[RR]: 1.00 p = 0.58), or intensive care unit/hospital stay (RR: 0.97 p = 0.66/RR:
0.98 p = 0.54, respectively). Conclusion: There was not a significant change in
risk of death, operative length, orhospital stay after a surgeon vacation.
PMID- 28511249
TI - Christopher W. Hess, MD, and Michael S. Okun, MD.
PMID- 28511250
TI - Update on Parkinson's Disease.
PMID- 28511252
TI - Diagnosis and Management of Parkinson's Disease.
AB - Despite numerous efforts to identify specific and sensitive biomarkers, the
diagnosis of Parkinson's disease (PD) is still based on clinical criteria that
include the presence of a combination of cardinal motor features (tremor,
rigidity, bradykinesia, and postural instability), other motor features
(including freezing of gait and abnormal postures), and numerous nonmotor
features. In addition, the presence of atypical features may suggest an
alternative diagnosis. Levodopa therapy remains the gold standard in the
management of motor features of PD. New formulations of levodopa and novel
delivery systems are currently being evaluated and gradually introduced in
clinical practice in an attempt to prevent or treat levodopa-related motor
complications. Dopamine agonists also play an important role as monotherapy in
mild or adjunctive therapy in moderately advanced disease. As the disease
progresses and patients develop complications from levodopa therapy, specifically
motor fluctuations and dyskinesias, deep brain stimulation becomes an alternative
therapeutic option. Clinical trials of experimental therapeutics are currently
fueling the PD therapeutic pipeline.
PMID- 28511253
TI - Pathophysiology and Management of Parkinsonian Tremor.
AB - Parkinson's tremor is one of the cardinal motor symptoms of Parkinson's disease.
The pathophysiology of Parkinson's tremor is different from that of other motor
symptoms such as bradykinesia and rigidity. In this review, the authors discuss
evidence suggesting that tremor is a network disorder that arises from distinct
pathophysiological changes in the basal ganglia and in the
cerebellothalamocortical circuit. They also discuss how interventions in this
circuitry, for example, deep brain surgery and noninvasive brain stimulation, can
modulate or even treat tremor. Future research may focus on understanding sources
for the large variability between patients in terms of treatment response, on
understanding the contextual factors that modulate tremor (stress, voluntary
movements), and on focused interventions in the tremor circuitry.
PMID- 28511251
TI - The Phenomenology of Parkinson's Disease.
AB - The motor symptoms of Parkinson's disease are not limited to the cardinal
symptoms of bradykinesia, rigidity, and resting tremor, but also include a
variety of interrelated motor phenomena such as deficits in spatiotemporal
planning and movement sequencing, scaling and timing of movements, and
intermuscular coordination that can be clinically observed. Although many of
these phenomena overlap, a review of the full breadth of the motor phenomenon can
aid in the diagnosis and monitoring of disease progression.
PMID- 28511254
TI - Genetic Forms of Parkinson's Disease.
AB - One of the greatest advances in Parkinson's disease (PD) research in the past two
decades has been a better understanding of PD genetics. Of the many candidate
genes investigated, the best studied include LRRK2, SNCA, VPS35, Parkin, PINK1,
and DJ1. The authors review the key clinical features of these monogenic forms,
as well as for the prevalent risk factor gene, GBA, including the phenotype,
clinical course, and treatment response. They also outline areas for future
investigation: longitudinal studies of PD's clinical course, the identification
of its premotor manifestations, and its specific mechanisms of pathogenicity.
PMID- 28511256
TI - Nonmotor Symptoms in Parkinson's Disease.
AB - Nonmotor symptoms (NMSs) in Parkinson's disease (PD) have become increasingly
recognized as major determinants of quality of life across cultures worldwide.
Behavioral symptoms include dementia, depression, anxiety, apathy, and fatigue.
Somatic symptoms include hypotension, constipation, diaphoresis, and pain.
However, somatic symptoms may also be intrinsic, such as dementia, and
iatrogenic, such as compulsive disorders. The authors address some of the more
common disorders, yet few have been the target of clinical trials.
PMID- 28511257
TI - Characterizing Cognitive Impairment in Parkinson's Disease.
AB - Cognitive impairment is a frequent complication in Parkinson's disease (PD),
though it can be heterogeneous in its presentation and progression. Cognitive
deficits vary among patients with regard to clinical features, severity, and
progression to dementia. A growing recognition of cognitive impairment in PD in
both the clinical and research settings has led to advances in diagnostic
criteria and improved understanding of the clinical phenotypes, associated
biomarkers, and underlying pathophysiology of both PD dementia and PD mild
cognitive impairment. Therapeutic interventions are geared to improve symptoms
and ideally to prevent cognitive decline. Here the authors summarize the current
research on the characterization of cognitive impairment in PD, with specific
attention focused on its clinical phenotype, associated neuropsychiatric and
prodromal features, pathological changes, genetic variations, and imaging and
biochemical biomarkers.
PMID- 28511258
TI - Management of Autonomic Dysfunction in Parkinson's Disease.
AB - Autonomic dysfunction is a frequent and important nonmotor feature of Parkinson's
disease (PD). Autonomic dysfunction in PD spans a broad clinical spectrum.
Cardiovascular dysfunction is characterized most prominently by orthostatic
hypotension. Gastrointestinal dysfunction can involve virtually all levels of the
gastrointestinal tract. Urinary dysfunction can entail either too frequent
voiding or difficulty voiding. Sexual dysfunction is frequent and frustrating for
both the patient and the partner. Alterations in sweating and body temperature
are not widely recognized, but often are present. The presence of effective
treatment for at least some aspects of autonomic dysfunction makes it vitally
important that the assessment of autonomic dysfunction be a regular component of
the neurologic history and examination for individuals with PD.
PMID- 28511255
TI - Motor Complications of Dopaminergic Medications in Parkinson's Disease.
AB - Motor complications are a consequence of the chronic treatment of Parkinson's
disease (PD) and include motor fluctuations (wearing-off phenomenon) and levodopa
induced dyskinesia. Both can have a significant impact on functionality and
quality of life; thus, proper recognition and management is essential. The
phenomenology and temporal relationship of motor complications to the schedule of
levodopa dosing can be helpful in characterizing them. There are several
therapeutic approaches to motor complications, including pharmacological and
surgical options. The authors summarize the different types of motor
complications according to phenomenology and the currently available medical
treatments, including ongoing trials for the management of this condition.
PMID- 28511260
TI - Botulinum Toxin Therapy for Parkinson's Disease.
AB - Botulinum toxin (BoNT) therapy is frequently employed in the treatment of
Parkinson's disease (PD) symptoms. It can effectively ameliorate the symptoms of
cervical dystonia, blepharospasm, sialorrhea, and hyperactive bladder. It is
increasingly being used for additional PD-related indications including limb
dystonia, oromandibular dystonia, tremors, constipation, dysphagia,
gastroparesis, and sweating dysfunction. Botulinum toxin treatment has mostly
local side effects and does not interfere with dopaminergic therapies prescribed
for PD. With the exception of dystonia and sialorrhea, most evidence for BoNT
efficacy is derived from studies conducted in nonparkinsonian populations. Thus,
the data to inform typical response pattern and side-effect profile in PD are
still evolving. Nevertheless, BoNT is widely used and is an important tool in the
PD-treatment arsenal. In this review, the authors discuss the current literature
on the use of BoNT in various PD-related motor and nonmotor disorders.
PMID- 28511259
TI - Impulse Control Disorders and Related Complications of Parkinson's Disease
Therapy.
AB - Impulsive and compulsive behaviors in Parkinson's disease (PD) patients are most
often attributed to dopamine agonist therapy; dysregulation of the
mesocorticolimbic system accounts for this behavioral phenotype. The clinical
presentation is commonly termed impulse control disorder (ICD): Behaviors include
hypersexuality, compulsive eating, shopping, pathological gambling, and
compulsive hobby participation. However, not all PD individuals taking dopamine
agonists develop these behavioral changes. In this review, the authors focus on
the similarities between the phenotypic presentation of ICDs with that of other
reward-based behavioral disorders, including binge eating disorder, pathological
gambling, and substance use disorders. With this comparison, we emphasize that
the transition from an impulsive to compulsive behavior likely follows a ventral
to dorsal striatal pattern, where an altered dopaminergic reward system underlies
the emergence of these problematic behaviors. The authors discuss the
neurobiological similarities between these latter disorders and ICDs, emphasizing
similar pathophysiological processes and discussing treatment options that have
potential for translation to PD patients.
PMID- 28511261
TI - Current Practice and the Future of Deep Brain Stimulation Therapy in Parkinson's
Disease.
AB - Deep brain stimulation (DBS) is an effective therapy for Parkinson's disease
patients experiencing motor fluctuations, medication-resistant tremor, and/or
dyskinesia. Currently, the subthalamic nucleus and the globus pallidus internus
are the two most widely used targets, with individual advantages and
disadvantages influencing patient selection. Potential DBS patients are selected
using the few existing guidelines and the available DBS literature, and many
centers employ an interdisciplinary team review of the individual's risk-benefit
profile. Programmed settings vary based on institution- or physician-specific
protocols designed to maximize benefits and limit adverse effects. Expectations
should be realistic and clearly defined during the evaluation process, and each
bothersome symptom should be addressed in the context of building the risk
benefit profile. Current DBS research is focused on improved symptom control, the
development of newer technologies, and the improved efficiency of stimulation
delivery. Techniques deliver stimulation in a more personalized way, and methods
of adaptive DBS such as closed-loop approaches are already on the horizon.
PMID- 28511263
TI - Diagnosis and Treatment of Functional (Psychogenic) Parkinsonism.
AB - Functional (psychogenic) parkinsonism (FP) is recognized by the mandatory
combination of marked slowness without progressive decrement on repetitive manual
tasks and variable resistance against passive movements in the absence of
cogwheel rigidity. Other functional phenotypes, such as functional tremor and
functional gait impairment, may coexist. Although neither necessary nor
sufficient for the diagnosis of FP, supportive historical clues include the
sudden onset of symptoms and absent or nonphysiologic response to levodopa. In
selected cases where examination features remain insufficient to render a
clinically definite FP diagnosis, normal dopaminergic transporter imaging (DAT
scan) confirms "laboratory supported" FP. The management of FP begins with
diagnostic debriefing, as the full acceptance of the diagnosis is critical in
ensuring patient involvement in individualized psychoeducation, psychotherapy,
and physical and occupational therapy.
PMID- 28511262
TI - Recognizing Atypical Parkinsonisms: "Red Flags" and Therapeutic Approaches.
AB - The overlap of signs and symptoms between Parkinson's disease and the atypical
parkinsonian syndromes, such as progressive supranuclear palsy, multiple system
atrophy, corticobasal syndrome and dementia with Lewy bodies, can render clinical
diagnoses challenging. The continued evolution of diagnostic criteria to reflect
the increasingly recognized heterogeneous presentations of these diseases further
complicates timely recognition and diagnosis. In this review, we provide a
diagnostic approach to the classic atypical parkinsonian syndromes, with an
emphasis on the key clinical and pathological features of each and the
recognition of "red flags" in the setting of recent advances in diagnosis and
treatment.
PMID- 28511264
TI - Visceral Artery Aneurysms and Pseudoaneurysms: Retrospective Analysis of
Interventional Endovascular Therapy of 43 Aneurysms.
AB - Purpose To evaluate the results of interventional endovascular therapy of
incidental and symptomatic visceral artery aneurysms in the elective and
emergency situation. Materials and Methods 43 aneurysms in 38 patients (19
female, 19 male, mean age: 57 +/- 16 years [18 - 82]) were treated between 2011
and 2015. The characteristics of the aneurysms (true vs. false aneurysm, size,
etiology, location, symptoms) were considered. Furthermore, we evaluated the
intervention with respect to technical success, embolic/occlusive agents used,
therapy-associated complications and post-interventional follow-up. Results 23
true aneurysms (maximum diameter: 22 +/- 18 mm [11 - 67 mm]) and 20 false
aneurysms (maximum diameter: 9 +/- 33 mm [3 - 150 mm]) were evaluated. The
splenic (n = 14) and renal arteries (n = 18) were most frequently affected. The
etiology was most commonly degenerative-atherosclerotic (47 %) or iatrogenic post
operative (19 %). 18/48 interventions were performed due to active bleeding.
False aneurysms were associated significantly more often with active bleeding (63
vs. 25 %, p = 0.012). 41/48 treatments were technically successful. Re
intervention was necessary 6 times. In 2 cases the endovascular approach did not
succeed. There was a complication rate of 10 %, whereby only 4 minor and 1 major
complications occurred. No patient suffered from permanent sequelae. Aneurysms
were primarily treated by using coils and if necessary additional embolic agents
(liquid embolic agent or vascular plugs) (75 %). In the follow-up period,
reperfusion of treated aneurysms occurred at a rate of 7 % (n = 3). Conclusion
Interventional endovascular therapy of visceral artery aneurysms is safe and
effective in the elective treatment of incidental aneurysms as well as in
significantly more frequent hemorrhaging false aneurysms in the emergency
situation. Key points . Interventional endovascular therapy of visceral artery
aneurysms is safe and effective.. . In more than 60 % of cases visceral artery
pseudoaneurysms are associated significantly more often with a history of
bleeding or acute bleeding. Hence, there is a need for (interventional) therapy
even in small pseudoaneurysms.. . Follow-up seems to be useful to detect
reperfusion as manifestation of treatment failure.. Citation Format . Ruhnke H,
Kroncke TJ, . Visceral Artery Aneurysms and Pseudoaneurysms: Retrospective
Analysis of Interventional Endovascular Therapy of 43 Aneurysms. Fortschr
Rontgenstr 2017; 189: 632 - 639.
PMID- 28511265
TI - Diagnostic Value of Diffusion-Weighted MRI for Tumor Characterization,
Differentiation and Monitoring in Pediatric Patients with Neuroblastic Tumors.
AB - Purpose We explored the diagnostic value of diffusion-weighted MRI (DWI) for
tumor characterization, differentiation and therapy monitoring in pediatric
patients with extracranial neuroblastic tumors. Materials and Methods All 29
patients (14 girls, median age: 3 years) with neuroblastoma (NB, n = 19),
ganglioneuroblastoma (GNB, n = 4) and ganglioneuroma (GN, n = 6) who had had at
least one in-house DWI examination since 2005 were identified and retrospectively
analyzed. Two independent blinded readers measured ADC values (unit: 10-3 mm2/s)
and signal intensity ratios (SIRs) of the primary tumor and, if applicable, of
the tumor after chemotherapy, metastases and tumor relapse. Results The pre
treatment ADC was 0.90 +/- 0.23 in NB/GNB and 1.70 +/- 0.36 in GN without overlap
between the two entities for both readers, 0.67 +/- 0.14 in metastases and 0.72
+/- 0.18 in tumor relapse. With chemotherapy, mean ADC increased to 1.54 +/- 0.33
in NB/GNB and to 1.23 +/- 0.27 in metastases (p < 0.05). The median SIRs of
various tumor lesions vs. liver, vs. muscle tissue and vs. adjacent tissue were
significantly higher on DWI (range: 2.4 - 9.9) than on ce-T1w (range: 1.0 - 1.8,
all p < 0.05). The coefficient of variation (CV) was <= 8.0 % for ADC and <= 16.4
% for signal intensity data. Conclusion Based on mean ADC, DWI distinguishes
between NB/GNB and GN with high certainty and provides plausible quantitative
data on tumor response to therapy. Lesion conspicuity, as measured by SIR, is
superior on DWI, compared to ce-T1w. DWI as a noninvasive, radiation-free and
widely available imaging technique should be an integral part of MR imaging for
neuroblastic tumors and should undergo prospective evaluation in multicenter
studies. Key Points . DWI reliably distinguishes
neuroblastoma/ganglioneuroblastoma from ganglioneuroma, based on the mean ADC.. .
DWI provides plausible quantitative data on tumor response to chemotherapy.. .
DWI offers highly superior lesion conspicuity compared to contrast-enhanced T1w
imaging.. . DWI should be considered a standard for imaging neuroblastic tumors..
Citation Format . Neubauer H, Li M, Muller VR et al. Diagnostic Value of
Diffusion-Weighted MRI for Tumor Characterization, Differentiation and Monitoring
in Pediatric Patients with Neuroblastic Tumors. Fortschr Rontgenstr 2017; 189:
640 - 650.
PMID- 28511266
TI - Diagnosis and Differential Diagnosis of Hydrocephalus in Adults.
AB - Purpose Hydrocephalus is caused by an imbalance of production and absorption of
cerebrospinal fluid (CSF) or obstruction of its pathways, resulting in
ventricular dilatation and increased intracranial pressure. Imaging plays a
crucial role in the diagnosis, differential diagnosis and planning of treatment.
Methods This review article presents the different types of hydrocephalus und
their typical imaging appearance, describes imaging techniques, and discusses
differential diagnoses of the different forms of hydrocephalus. Results and
Conclusion Imaging plays a central role in the diagnosis of hydrocephalus. While
magnetic resonance (MR) imaging is the first-line imaging modality, computed
tomography (CT) is often the first-line imaging test in emergency patients. Key
points . Occlusive hydrocephalus is caused by obstruction of CSF pathways.. .
Malabsorptive hydrocephalus is caused by impaired CSF absorption.. . The MR
imaging protocol should always include sagittal high-resolution T2-weighted
images.. . When an inflammatory etiology is suspected, imaging with contrast
agent administration is necessary.. Citation Format . Langner S, Fleck S, Baldauf
J et al. Diagnosis and Differential Diagnosis of Hydrocephalus in Adults.
Fortschr Rontgenstr 2017; 189: 728 - 739.
PMID- 28511267
TI - Thermal Ablation of Lung Tumors: Focus on Microwave Ablation.
AB - Background Image-guided thermal ablation can be used for the treatment of
medically inoperable primary and metastatic lung cancer. These techniques are
based on the heating up or freezing (cryoablation) of a volume of tissue around a
percutaneous applicator that induces necrosis of the tumor. Method The English
language literature concerning thermal ablation of the lung was reviewed.
Radiofrequency ablation (RFA) is the most widely performed and investigated of
these techniques. Microwave ablation (MWA) represents a relatively new
alternative that shares the same indications and is conducted in a very similar
fashion as RFA. It has been experimentally and clinically shown that MWA produces
larger, more spherical ablation zones over shorter periods of time compared to
RFA. Seven different MWA systems are available in Europe and the USA with
significant differences in the size and shape of the produced ablation zones.
Results The types of complications caused by MWA and their rates of occurrence
are very similar to those caused by RFA. The local progression rates after MWA of
lung malignancies vary between 0 % and 34 % and are similar to those in the RFA
literature. Conclusion Despite technical improvements, the current generation of
MWA systems has comparable clinical outcomes to those of RFA. Key Points . MWA
is a safe technique that should be considered one of the treatment options for
medically inoperable lung tumors. . As thermal ablations of lung tumors are
becoming more frequent, radiologists should be acquainted with the post-ablation
imaging characteristics. . Although MWA has some theoretical advantages over RFA,
the clinical outcomes are similar. Citation Format . Vogl TJ, Nour-Eldin NA,
Albrecht MH et al. Thermal Ablation of Lung Tumors: Focus on Microwave Ablation.
Fortschr Rontgenstr 2017; 189: 828 - 843.
PMID- 28511268
TI - ?
PMID- 28511269
TI - The role of birds in arboviral disease surveillance in Harris County and the City
of Houston, Texas.
AB - Avian arboviral surveillance is an integral part of any disease-based integrated
mosquito control program. The Harris County Public Health Mosquito and Vector
Control Division has performed arboviral surveillance in the wild birds of Harris
County and the City of Houston since 1965. Blood samples from live trapped birds
were tested for arboviral antibodies to West Nile virus (WNV), St. Louis
encephalitis, Eastern equine encephalitis, and Western equine encephalitis. A
dead bird surveillance program was created in 2002 with the arrival of WNV in
Harris County. Since implementation, the program has detected considerable
variability in viral activity with annual WNV seroprevelance rates ranging from
2.9% to 17.7%, while the percentage of positive dead birds has ranged from 0.3%
to 57.2%. In 2015, 1,345 live birds were sampled and 253 dead birds were tested,
with WNV incidence rates of 16.5% and 5.9%, respectively.
PMID- 28511270
TI - Laboratory and semi-field evaluations of two (transfluthrin) spatial repellent
devices against Aedes aegypti (L.) (Diptera: Culicidae).
AB - Two transfluthrin-based spatial repellent products (Raid Dual Action Insect
Repellent and Home Freshener and Raid Shield (currently not commercially
available), SC Johnson, Racine WI) were evaluated for spatial repellent effects
against female Aedes aegypti (L.) mosquitoes under laboratory (wind tunnel) and
semi-field (outdoor enclosure) conditions. The placement of either product in the
wind tunnel significantly reduced host-seeking behaviors. The mean baseline
(control) landing counts for the Raid Dual Action and Raid Shield were reduced by
95% and 74% respectively. Mean probing counts for the Raid Dual Action were
reduced by 95%, while the probing counts for the Raid Shield were decreased by
69%. Baseline blood-feeding success was significantly reduced for both
treatments: Raid Dual Action (100%) and Raid Shield (96%). Semi-field evaluations
were conducted in outdoor enclosures at the Navy Entomology Center of Excellence,
Jacksonville, Florida. A moderate reduction in mosquito entry into military style
tents resulted when either product was placed near the tent opening. The Raid
Shield reduced mosquito entry into tents by 88%, while the Dual Action decreased
entry by 66%.
PMID- 28511271
TI - Georgia's collaborative approach to expanding mosquito surveillance in response
to Zika virus: a case study.
AB - : Zika virus (ZIKV) was declared an international public health emergency by the
World Health Organization on February 1, 2016. Due to the known and estimated
range of the ZIKV mosquito vectors, southern and central US states faced
increased risk of ZIKV transmission. With the state of Georgia hosting the
world's busiest international airport, a climate that supports the ZIKV vectors,
and limited surveillance (13 counties) and response capacity, the Department of
Public Health (DPH) was challenged to respond and prevent ZIKV transmission. This
case study describes and evaluates the state's surveillance capacity before and
after the declaration of ZIKV as a public health emergency. METHOD: We analyzed
surveillance data from the DPH to compare the geographical distribution of
counties conducting surveillance, total number, and overall percentage of
mosquito species trapped in 2015 to 2016. Counties conducting surveillance before
and after the identification of the ZIKV risk were mapped using ArcMap 10.4.1.
Using SAS (version 9.2) (SAS Institute, Inc, Cary, NC), we performed the
independent 2 sample t test to test for differences in prevalence in both years,
and a chi2 analysis to test for differences between numbers of species across the
13 counties. In addition, weighted frequency counts of mosquitoes were used to
test (chi2) an association between major mosquito vector species and 7 urban
counties. Lastly, using data from 2012-2016, a time-trend analysis was conducted
to evaluate temporal trends in species prevalence. RESULTS: From 2015 to 2016,
surveillance increased from 13 to 57 (338% increase) counties geographically
dispersed across Georgia. A total of 76,052 mosquitoes were trapped and
identified in 2015 compared to 144,731 (90.3% increase) in 2016. Significant
differences between species (P<.001) and significant associations (P<.0001)
between 7 urban counties and major mosquito vectors were found. Significant
differences in prevalence were found between several species and year
highlighting species-year temporal trends. CONCLUSIONS: The DPH collaborative
response to ZIKV allowed a rapid increase in its surveillance footprint. Existing
and new partnerships were developed with the military and local health
departments to expand and share data. This additional surveillance data allowed
DPH to make sound public health decisions regarding mosquito-borne disease risks
and close gaps in data related to vector distribution.
PMID- 28511272
TI - A location-specific spreadsheet for estimating Zika risk and timing for Zika
vector surveillance, using US military facilities as an example.
AB - Local Zika virus transmission in the United States involving one or both of the
known vector species, Aedes aegypti and Ae. albopictus, is of major concern. To
assist efforts to anticipate the risks of transmission, we developed an Excel
spreadsheet tool that uses vector and virus temperature thresholds, remotely
sensed maximum temperature, and habitat suitability models to answer the
questions: "is Zika transmission likely here?" and "when should we conduct vector
surveillance?" An example spreadsheet, updated regularly and freely available,
uses near real-time and forecast temperature data to generate guidance, based on
a novel four level Zika risk code, for 733 US military facilities in the 50
states, the District of Columbia, and the territories of Guam and Puerto Rico.
PMID- 28511273
TI - Biosurveillance and morphological variations of larvae and pupae of common
malaria vectors, Anopheles (Anopheles) Hyrcanus group species in the Republic of
Korea.
AB - A total of 4,576 Anopheles (Anopheles) Hyrcanus Group larvae belonging to 6
species (An. belenrae, An. kleini, An. sinensis, An. pullus, An. lesteri, and An.
sineroides) were collected from 7 different habitat types in 3 provinces of the
Republic of Korea. The occurrence and relative abundance of 6 Anopheles species
were noted. The descriptions in the article of the waxy body ornamentations or
patterns of An. (Ano.) Hyrcanus Group larvae and pupae may be useful for rapid
field species identification when conducting larval mosquito surveillance.
PMID- 28511274
TI - A case of Chagas cardiomyopathy following infection in south central Texas.
AB - Between 5 and 8 million people globally are infected with Trypanosoma cruzi, the
causative parasitic agent of Chagas disease. The vast majority of incident
infections originate in pockets of Latin America where domestic vector-borne
transmission cycles are more common. Since 1955, when the first locally-acquired
case was reported, fewer than 30 autochthonous cases have been documented in the
United States. We describe the case of an 18-year-old US Air Force trainee, a
native Texan with no travel history beyond the continental United States, who
screened positive for T cruzi infection on blood donation and was subsequently
found to have chronic Chagasic cardiomyopathy. This is the first documented case
of Chagas disease in a US military trainee and one of the first known
autochthonous cases of Chagasic cardiomyopathy in a Texas resident. Diagnostic,
therapeutic, and military implications are discussed.
PMID- 28511275
TI - Direct detection of Leishmania from clinical samples.
AB - The ability to rapidly and accurately diagnose leishmaniasis is a military
priority. Testing was conducted to evaluate diagnostic sensitivity and
specificity of field-expedient Leishmania genus and visceral Leishmania specific
dual-fluorogenic, hydrolysis probe (TaqMan), polymerase chain reaction assays
previously established for use in vector surveillance. Blood samples of patients
with confirmed visceral leishmaniasis and controls without the disease from
Baringo District, Kenya, were tested. Leishmania genus assay sensitivity was 100%
(14/14) and specificity was 84% (16/19). Visceral Leishmania assay sensitivity
was 93% (13/14) and specificity 80% (4/5). Cutaneous leishmaniasis (CL) skin
scrapes of patients from Honduras were also evaluated. Leishmania genus assay
sensitivity was 100% (10/10). Visceral Leishmania assay specificity was 100%
(10/10) from cutaneous leishmaniasis samples; no fluorescence above background
was reported. These results show promise in a rapid, sensitive, and specific
method for Leishmania direct detection from clinical samples.
PMID- 28511276
TI - New records, distribution, and updated checklists of old world Phlebotomine sand
flies, with emphasis on Africa, southwest Asia, and central Asia.
AB - This article includes new records, distribution, and updated checklist of
Phlebotomine sand flies (Psychodidae, Diptera) in the Old World (Africa including
West Indian Ocean Islands, Southwest Asia, and Central Asia) based on specimen
collections housed in different repositories worldwide. About 124 species have
primary types housed in 5 repositories including holotypes (45 species, 4
subspecies), syntypes (28 species, 3 subspecies), "types" (14 species), allotypes
(10 species), paratypes (36 species, 3 subspecies), lectotypes (13 species), and
cotype (5 species), mounted on 671 slides. New abbreviations were proposed for 2
subgenera in the genus Phlebotomus and 6 subgenera in the genus Sergentomyia. New
country records were noted in Phlebotomus (4 species in 4 subgenera in 7
countries) and Sergentomyia (10 species in 4 subgenera in 8 countries). For
species diversity in the Old World, Phlebotomus includes 92 species and 7
subspecies in 9 subgenera, while Sergentomyia includes 166 species and 16
subspecies in 12 subgenera. A total of 95 species and 7 subspecies of 2 genera
(Phlebotomus and Sergentomyia) were recorded in Africa while about 26 species and
16 subspecies in Southwest Asia and Central Asia.
PMID- 28511277
TI - Operational mosquito and vector-borne diseases surveillance at Incirlik Air Base,
Turkey.
AB - Arboviruses on Incirlik Air Base, Turkey, pose a threat to military personnel and
civilians, but might also be relevant for understanding the threats in
neighboring conflict zones such as Syria. We reviewed 6 years of mosquito and
arbovirus surveillance at Incirlik Air Base. Over 6,000 mosquitoes were
identified as Aedes caspius, Anopheles claviger, Culex mimeticus, Cx. perexiguus,
Cx. pipiens, Cx. sinaiticus, and Culiseta longiareolata. Almost all of the
mosquitoes (more than 90%) were Cx. perexiguus or Cx. pipiens. Both West Nile
virus and Sindbis virus were detected in 6 mosquito pools among collections made
in 2013, 2014, and 2015.
PMID- 28511278
TI - Vector-borne diseases of public health importance for personnel on military
installations in the United States.
PMID- 28511279
TI - Blast-associated traumatic brain injury in the military as a potential trigger
for dementia and chronic traumatic encephalopathy.
AB - Traumatic brain injuries (TBIs) resulting from blast exposures have significantly
affected US military personnel throughout the world, particularly in Iraq and
Afghanistan. From 2000-2016, more than 350,000 military service members were
diagnosed with a TBI. Since the majority of blast-related TBIs are classified as
mild with no definitive findings on physical examination or diagnostic studies,
it is difficult to accurately diagnose individuals inflicted with such injuries.
There are likely far more mild TBIs that remain undiagnosed in the military.
Traumatic brain injury is a serious public health concern since it can lead to
long-term neuropsychiatric changes such as posttraumatic stress disorder and
various forms of dementia. Blast-related TBI has also been linked with
neuropsychiatric dysfunction that is commonly seen in athletes that have suffered
chronic traumatic encephalopathy. Further research is needed to aid in
prevention, diagnostic studies, and care of military service members and veterans
who have suffered a TBI.
PMID- 28511280
TI - Challenges of practicing environmental epidemiology in the US military.
PMID- 28511281
TI - Indirect military occupational lead exposure to children at home: a case report.
PMID- 28511282
TI - Livedoid Vasculopathy.
PMID- 28511283
TI - A different inhibitor is required for overcoming entecavir resistance: a
comparison of four rescue therapies in a retrospective study.
AB - AIMS: Little clinical data are available regarding re-establishing the effective
inhibition of entecavir (ETV)-resistant mutants. In this retrospective study, we
aimed to compare the efficacies of four treatment regimens as rescue therapy for
those chronic hepatitis B (CHB) patients with ETV resistance. METHODS: A total of
65 patients with ETV resistance were assigned either with tenofovir disoproxil
fumarate (TDF) monotherapy (n = 21), ETV (0.5 mg) plus adefovir (ADV) combination
therapy (n = 19), ETV (1.0 mg) monotherapy (n = 11) or ETV (0.5 mg) plus TDF
combination therapy (n = 14). The efficacy and safety of four treatment regimens
were compared. RESULTS: There were no significant differences among the four
study groups in baseline characteristics, including HBV DNA levels (chi2 =
0.749, P = 0.862) and hepatitis B e antigen-positivity (chi2 = 0.099, P =
0.992). The median reduction in serum HBV DNA level from baseline at week 48 was
2.37 +/- 1.07 log10 IU ml-1 , -2.16 +/- 0.81 log10 IU ml-1 , -1.17 +/- 1.23 log10
IU ml-1 and -2.49 +/- 1.10 log10 IU ml-1 , respectively (F = 4.078, P = 0.011).
The TDF group and ETV (0.5 mg) + TDF group have the highest undetectable HBV DNA
rate (76.19% vs. 78.57%) compared to the ETV (0.5 mg) + ADV group and the ETV
(1.0 mg) group (63.16% vs. 18.18%, respectively). Two patients in the ETV (1.0
mg) group experienced virological breakthrough at week 48 and was attributed to
poor drug adherence. CONCLUSIONS: TDF monotherapy appeared to deliver the highest
undetectable HBV DNA rate in patients with ETV resistance, and ADV plus ETV
combination therapy could be another choice for patients with financial
restraint.
PMID- 28511284
TI - Non-mix fragrances are top sensitizers in consecutive dermatitis patients - a
cross-sectional study of the 26 EU-labelled fragrance allergens.
AB - BACKGROUND: For cosmetics, it is mandatory to label 26 fragrance substances,
including all constituents of fragrance mix I (FM I) and fragrance mix II (FM
II). Earlier reports have not included oxidized R-limonene [hydroperoxides of R
limonene (Lim-OOH)] and oxidized linalool [hydroperoxides of linalool (Lin-OOH)],
and breakdown testing of FM I and FM II has mainly been performed in selected,
mix-positive patients. OBJECTIVES: To report the prevalence of sensitization to
the 26 fragrances, and to assess concomitant reactivity to FM I and/or FM II.
METHODS: A cross-sectional study on consecutive dermatitis patients patch tested
with the 26 fragrances and the European baseline series from 2010 to 2015 at a
single university clinic was performed. RESULTS: Of 6004 patients, 940 (15.7%,
95%CI: 14.7-16.6%) were fragrance-sensitized. Regarding the single fragrances,
most patients were sensitized to Lin-OOH (3.9%), Evernia furfuracea (3.0%), Lim
OOH (2.5%), and hydroxyisohexyl 3-cyclohexene carboxaldehyde (2.1%).
Significantly fewer patients were 'FM I-positive and constituent-positive' than
'FM II-positive and constituent-positive' (32.7% versus 57.0%, p < 0.0001).
Additionally, significantly more patients were 'FM II-negative but constituent
positive' than 'FM I-negative but constituent-positive' (12.4% versus 3.2%, p =
0.0008). CONCLUSIONS: Non-mix fragrances are the most important single fragrance
allergens among consecutive patients. The test concentration of the single FM I
constituents should be increased when possible.
PMID- 28511285
TI - Association of Increased F4/80high Macrophages With Suppression of Serum-Transfer
Arthritis in Mice With Reduced FLIP in Myeloid Cells.
AB - OBJECTIVE: Macrophages are critical in the pathogenesis of rheumatoid arthritis
(RA). We recently demonstrated that FLIP is necessary for the differentiation
and/or survival of macrophages. We also showed that FLIP is highly expressed in
RA synovial macrophages. This study was undertaken to determine if a reduction in
FLIP in mouse macrophages reduces synovial tissue macrophages and ameliorates
serum-transfer arthritis. METHODS: Mice with Flip deleted in myeloid cells
(Flipf/f LysMc/+ mice) and littermate controls were used. Arthritis was induced
by intraperitoneal injection of K/BxN serum. Disease severity was evaluated by
clinical score and change in ankle thickness, and joints were examined by
histology and immunohistochemistry. Cells were isolated from the ankles and bone
marrow of the mice and examined by flow cytometry, real-time quantitative reverse
transcriptase-polymerase chain reaction, or Western blotting. RESULTS: In
contrast to expectations, Flipf/f LysMc/+ mice developed more severe arthritis
early in the clinical course, but peak arthritis was attenuated and the
resolution phase more complete than in control mice. Prior to the induction of
serum-transfer arthritis, the number of tissue-resident macrophages was reduced.
On day 9 after arthritis induction, the number of F4/80high macrophages in the
joints of the Flipf/f LysMc/+ mice was not decreased, but increased. FLIP was
reduced in the F4/80high macrophages in the ankles of the Flipf/f LysMc/+ mice,
while F4/80high macrophages expressed an antiinflammatory phenotype in both the
Flipf/f LysMc/+ and control mice. CONCLUSION: Our observations suggest that
reducing FLIP in macrophages by increasing the number of antiinflammatory
macrophages may be an effective therapeutic approach to suppress inflammation,
depending on the disease stage.
PMID- 28511287
TI - Generation and characterization of highly purified canine Schwann cells from
spinal nerve dorsal roots as potential new candidates for transplantation
strategies.
AB - Schwann cells are promising candidates for transplantation strategies in the
central nervous system by promoting axonal regeneration. The dog represents a
translational model for human spinal cord injury (SCI) for studies with new
repair strategies after intervertebral disk herniation (IVDH). To overcome the
necessity for an additional surgical procedure, for the first time a protocol for
the isolation and purification of canine Schwann cells from spinal nerve biopsies
during standard hemilaminectomy in IVDH-affected paraplegic dogs for potential
transplantation has been developed. Purity was assessed by flow cytometry. The
results were compared with biopsies from dogs without SCI. Within 26 +/- 4 days,
90.2 +/- 8.8% p75 neurotrophin receptor (p75NTR )-positive cells were achieved in
IVDH dogs. The total cell count in acute/subacute and chronic IVDH
(acute/subacute: 6.82 +/- 6.36 * 106 ; chronic: 2.29 +/- 2.00 * 106 ) differed
significantly (p = 0.0120) at the potential time point of transplantation. No
differences in culture period and purity were detected between dogs with and
without IVDH. Despite the small sample size and the altered environment, the
isolation of Schwann cells was successful. Negative influences on isolation and
purification due to potential pathological changes at the biopsy site of IVDH
diseased dogs were ruled out by comparison of Schwann cell pellets from diseased
and control dogs. Finally, the functionality of Schwann cells from dogs with IVDH
was outlined in co-culture experiments with canine dorsal root ganglion neurons.
In conclusion, nerve root biopsies provide a sufficient number of highly purified
and functional Schwann cells within a useful time period for novel therapeutic
strategies in dogs with SCI.
PMID- 28511288
TI - Tele-Health Followup Strategy for Tight Control of Disease Activity in Rheumatoid
Arthritis: Results of a Randomized Controlled Trial.
AB - OBJECTIVE: To test the effect of patient-reported outcome (PRO)-based tele-health
followup for tight control of disease activity in patients with rheumatoid
arthritis (RA), and the differences between tele-health followup performed by
rheumatologists or rheumatology nurses. METHODS: A total of 294 patients were
randomized (1:1:1) to either PRO-based tele-health followup carried out by a
nurse (PRO-TN) or a rheumatologist (PRO-TR), or conventional outpatient followup
by physicians. The primary outcome was a change in the Disease Activity Score in
28 joints (DAS28) after week 52. Secondary outcomes were physical function,
quality of life, and self-efficacy. The noninferiority margin was a DAS28 score
change of 0.6. Mean differences were estimated following per protocol, intent-to
treat (ITT), and multivariate imputation analysis. RESULTS: Overall, patients had
low disease activity at baseline and end followup. Demographics and baseline
characteristics were similar between groups. Noninferiority was established for
the DAS28. In the ITT analysis, mean differences in the DAS28 score between PRO
TR versus control were -0.10 (90% confidence interval [90% CI] -0.30, 0.13) and
0.19 (90% CI -0.41, 0.02) between PRO-TN versus control. When including 1 yearly
visit to the outpatient clinic, patients in PRO-TN had mean +/- SD 1.72 +/- 1.03
visits/year, PRO-TR had 1.75 +/- 1.03 visits/year, and controls had 4.15 +/- 1.0
visits/year. This included extra visits due to inflammatory flare. CONCLUSION:
Among RA patients with low disease activity or remission, a PRO-based tele-health
followup for tight control of disease activity in RA can achieve similar disease
control as conventional outpatient followup. The degree of disease control did
not differ between patients seen by rheumatologists or rheumatology nurses.
PMID- 28511286
TI - Who achieves low risk drinking during alcohol treatment? An analysis of patients
in three alcohol clinical trials.
AB - BACKGROUND AND AIMS: There is evidence that low-risk drinking is possible during
the course of alcohol treatment and can be maintained following treatment. Our
aim was to identify characteristics associated with low-risk drinking during
treatment in a large sample of individuals as they received treatment for alcohol
dependence. DESIGN: Integrated analysis of data from the Combined
Pharmacotherapies and Behavioral Intervention (COMBINE) study, Project MATCH
(Matching Alcoholism Treatments to Client Heterogeneity) and the United Kingdom
Alcohol Treatment Trial (UKATT) using repeated-measures latent class analysis to
identify patterns of drinking and predictors of low-risk drinking patterns during
treatment. SETTING: United States and United Kingdom. PARTICIPANTS: Patients (n =
3589) with alcohol dependence receiving treatment in an alcohol clinical trial
were primarily male (73.0%), white (82.0%) and non-married (41.7%), with an
average age of 42.0 (standard deviation = 10.7). MEASUREMENTS: Self-reported
weekly alcohol consumption during treatment was assessed using the Form-90 and
validated with biological verification or collateral informants. FINDINGS: Seven
patterns of drinking during treatment were identified: persistent heavy drinking
(18.7% of the sample), increasing heavy drinking (9.6%), heavy and low-risk
drinking (6.7%), heavy drinking alternating with abstinence (7.9%), low-risk
drinking (6.8%), increasing low-risk drinking (10.5%) and abstinence (39.8%).
Lower alcohol dependence severity and fewer drinks per day at baseline
significantly predicted low-risk drinking patterns [e.g. each additional drink
prior to baseline predicted a 27% increase in the odds of expected classification
in heavy drinking versus low-risk drinking patterns; odds ratio = 1.27 (95%
confidence interval (CI) = 1.10, 1.47, P = 0.002]. Greater negative mood and more
heavy drinkers in the social network were significant predictors of expected
membership in heavier drinking patterns. CONCLUSIONS: Low-risk drinking is
achievable for some individuals as they undergo treatment for alcohol dependence.
Individuals with lower dependence severity, less baseline drinking, fewer
negative mood symptoms and fewer heavy drinkers in their social networks have a
higher probability of achieving low-risk drinking during treatment.
PMID- 28511289
TI - Brief Report: Group 3 Innate Lymphoid Cells in Human Enthesis.
AB - OBJECTIVE: Group 3 innate lymphoid cells (ILC3s) play a pivotal role in barrier
tissues such as the gut and the skin, two important sites of disease in
spondyloarthritis (SpA). This study was undertaken to investigate whether normal
or injured human enthesis, a key target tissue in early SpA, harbors ILC3s in
entheseal soft tissue and adjacent perientheseal bone. METHODS: Interspinous
ligament and spinous process bone from donors with no systemic inflammatory
disease were collected, enzymatically digested, and immunophenotyped. The
immunologic profile of entheseal cells was examined, and the transcriptional
profile of sorted ILC3s was compared to that of ILC3s isolated from SpA synovial
fluid (SF). To assess the ability of entheseal tissue to produce interleukin-17
(IL-17) and IL-22, entheseal digests were stimulated with IL-23 and IL-1beta.
Osteoarthritic and ruptured Achilles tendon tissue was examined histologically.
RESULTS: The proportion of ILCs in human entheseal soft tissue was higher than
that in peripheral blood (P = 0.008); entheseal soft tissue and perientheseal
bone both had a higher proportion of NKp44+ ILC3s (P = 0.001 and P = 0.043,
respectively). Studies of retinoic acid receptor-related orphan nuclear receptor
gammat (RORgammat), STAT3, and IL-23 receptor transcript expression validated the
entheseal ILC3 phenotype. Cytokine transcript expression was similar in ILC3s
isolated from enthesis and from SpA SF. Stimulation of normal entheseal digests
with IL-23/IL-1beta led to up-regulation of IL-17A transcript, and histologic
examination of injured/damaged entheses revealed the presence of RORgammat
expressing cells. CONCLUSION: This work shows that human enthesis harbors a
resident population of ILC3s, with the potential to participate in the
pathogenesis of SpA.
PMID- 28511290
TI - First use of antidepressant medication in male partners of women with breast
cancer in Denmark from 1998 to 2011.
AB - OBJECTIVE: A diagnosis of breast cancer disrupts the life of the patient, but
also the partner may experience adverse psychological effects. We examined
partners' risk for first use of antidepressant medication, as a proxy for
pharmacologically treated depression. METHODS: By linkage of national registers,
we identified 1 420 592 depression-free men living with a cancer-free female
partner in 1998 to 2011. During follow-up, breast cancer was diagnosed in female
partners of 26 256 men. In Poisson regression models, we estimated the rate
ratios for first use of antidepressant medication compared to partners of breast
cancer-free women. Cox regression analyses examined associations between exposed
partners' sociodemographic characteristics, somatic comorbidity, death of female
partner, and first use of antidepressant medication. RESULTS: Male partners of
women with breast cancer had an increased rate ratio of 1.08 (95% CI, 1.03-1.13)
for first use of antidepressant medication compared to the background population,
corresponding to excess absolute risk of 12 cases per 10 000 person-years. This
increased risk persisted throughout 14 years of follow-up. Higher age, shorter
education, somatic comorbidity, and death of female partner were associated with
increased risk among men whose partner had breast cancer. CONCLUSION: The modest,
but long term, increased risk for first use of antidepressant medication calls
for attention by health care professionals to symptoms of depression among
partners of breast cancer patients.
PMID- 28511292
TI - Role of Gut Inflammation in Altering the Monocyte Compartment and Its
Osteoclastogenic Potential in HLA-B27-Transgenic Rats.
AB - OBJECTIVE: To investigate the relationship between intestinal inflammation and
the central and peripheral innate immune system in the pathogenesis of HLA-B27
associated spondyloarthritis using an HLA-B27-transgenic (B27-Tg) rat model.
METHODS: The myeloid compartment of the blood and bone marrow (BM) of B27-Tg
rats, as well as HLA-B7-Tg and non-Tg rats as controls, was evaluated by flow
cytometry. Plasma from rats was assessed by enzyme-linked immunosorbent assay for
levels of CCL2 and interleukin-1alpha (IL-1alpha). Rats were treated with
antibiotics for 4 weeks, and the myeloid compartment of the blood and BM was
evaluated by flow cytometry. The osteoclastogenic potential of BM-derived cells
from antibiotic-treated rats, in the presence or absence of tumor necrosis factor
(TNF), was evaluated in vitro. RESULTS: B27-Tg rats had substantially higher
numbers of circulating Lin-CD172a+CD43low monocytes as compared to control
animals, and this was significantly correlated with higher levels of plasma CCL2.
Antibiotic treatment of B27-Tg rats markedly reduced the severity of ileitis,
plasma levels of CCL2 and IL-1alpha, and number of BM and blood Lin
CD172a+CD43low monocytes, a cell subset shown in the present study to have the
greatest in vitro osteoclastogenic potential. Antibiotic treatment also prevented
the TNF-dependent enhancement of osteoclastogenesis in B27-Tg rats. CONCLUSION:
Microbiota-dependent intestinal inflammation in B27-Tg rats directly drives the
systemic inflammatory and bone-erosive potential of the monocyte compartment.
PMID- 28511293
TI - Enterobacter aerogenes ZDY01 Attenuates Choline-Induced Trimethylamine N-Oxide
Levels by Remodeling Gut Microbiota in Mice.
AB - Trimethylamine N-oxide (TMAO), which is transformed from trimethylamine (TMA)
through hepatic flavin-containing monooxygenases, can promote atherosclerosis.
TMA is produced from dietary carnitine, phosphatidylcholine, and choline via the
gut microbes. Previous works have shown that some small molecules, such as
allicin, resveratrol, and 3,3-dimethyl-1-butanol, are used to reduce circulating
TMAO levels. However, the use of bacteria as an effective therapy to reduce TMAO
levels has not been reported. In the present study, 82 isolates were screened
from healthy Chinese fecal samples on a basal salt medium supplemented with TMA
as the sole carbon source. The isolates belonged to the family
Enterobacteriaceae, particularly to genera Klebsiella, Escherichia, Cronobacter,
and Enterobacter. Serum TMAO and cecal TMA levels were significantly decreased in
choline-fed mice treated with Enterobacter aerogenes ZDY01 compared with those in
choline-fed mice treated with phosphate-buffered saline. The proportions of
Bacteroidales family S24-7 were significantly increased, whereas the proportions
of Helicobacteraceae and Prevotellaceae were significantly decreased through the
administration of E. aerogenes ZDY01. Results indicated that the use of
probiotics to act directly on the TMA in the gut might be an alternative approach
to reduce serum TMAO levels and to prevent the development of atherosclerosis and
"fish odor syndrome" through the effect of TMA on the gut microbiota.
PMID- 28511294
TI - Genome Sequences of Spinach Deltapartitivirus 1, Spinach Amalgavirus 1, and
Spinach Latent Virus Identified in Spinach Transcriptome.
AB - Complete genome sequences of three new plant RNA viruses, Spinach
deltapartitivirus 1 (SpDPV1), Spinach amalgavirus 1 (SpAV1), and Spinach latent
virus (SpLV), were identified from a spinach (Spinacia oleracea) transcriptome
dataset. The RNA-dependent RNA polymerases (RdRps) of SpDPV1, SpAV1, and SpLV
showed 72%, 53%, and 93% amino acid sequence identities with the homologous RdRp
of the most closely related virus, respectively, suggesting that SpDPV1 and SpAV1
were novel viruses. Sequence similarity and phylogenetic analyses revealed that
SpDPV1 belonged to the genus Deltapartitivirus of the family Partitiviridae,
SpAV1 to the genus Amalgavirus of the family Amalgaviridae, and SpLV to the genus
Ilarvirus of the family Bromoviridae. Based on the demarcation criteria, SpDPV1
and SpAV1 are considered as novel species of the genera Deltapartitivirus and
Amalgavirus, respectively. This is the first report of these two viruses from
spinach.
PMID- 28511291
TI - Effect of Fatigue, Older Age, Higher Body Mass Index, and Female Sex on
Disability in Early Rheumatoid Arthritis in the Treatment-to-Target Era.
AB - OBJECTIVE: To compare disease activity and disability over 2 years in early
rheumatoid arthritis (RA) before and after implementation of treat-to-target
therapy and identify predictors of adverse outcome. METHODS: The Yorkshire Early
Arthritis Register (YEAR) recruited 725 patients with early RA between 2002 and
2009, treated with a step-up approach. The Inflammatory Arthritis Continuum study
(IACON) recruited cases between 2010 and 2014 and treated to target. A total of
384 IACON cases met 2010 American College of Rheumatology/European League Against
Rheumatism criteria. Latent growth curves of change in Disease Activity Score in
28 joints (DAS28) and the Health Assessment Questionnaire (HAQ) were compared
between YEAR and IACON. Latent class growth analysis identified trajectories of
change. Baseline predictors of trajectories were identified using logistic
regression. RESULTS: The mean DAS28 over 2 years was lower in IACON than in YEAR.
Latent trajectories of HAQ change in YEAR were high stable (21% of cohort),
moderate reducing (35%), and low reducing (44%). Only moderate reducing (66%) and
low reducing (34%) were seen in IACON. In both cohorts, female sex and fatigue
predicted adverse HAQ trajectories (high stable and moderate reducing). Odds
ratios (ORs) for moderate reducing compared to low reducing for women were 2.58
(95% confidence interval [95% CI] 1.69, 4.49) in YEAR and 5.81 (95% CI 2.44,
14.29) in IACON. ORs per centimeter fatigue visual analog score were 1.13 (95% CI
1.07, 1.20) in YEAR and 1.16 (95% CI 1.12, 1.20) in IACON. CONCLUSION: Treat-to
target therapy gave more favorable trajectories of change in DAS28 and HAQ, but
adverse HAQ trajectory was more likely in women with greater fatigue, suggesting
such patients would benefit from interventions to improve function as well as
reduce inflammation.
PMID- 28511295
TI - Anaerobic Ammonium-Oxidizing Bacteria in Cow Manure Composting.
AB - Composting is widely used to transform waste into valuable agricultural organic
fertilizer. Anaerobic ammonium-oxidizing (anammox) bacteria play an important
role in the global nitrogen cycle, but their role in composting remains poorly
understood. In the present study, the community structure, diversity, and
abundance of anammox bacteria were analyzed using cloning and sequencing methods
by targeting the 16S rRNA gene and the hydrazine oxidase gene (hzo) in samples
isolated from compost produced from cow manure and rice straw. A total of 25
operational taxonomic units were classified based on 16S rRNA gene clone
libraries, and 14 operational taxonomic units were classified based on hzo gene
clone libraries. The phylogenetic tree analysis of the 16S rRNA gene and deduced
HZO protein sequences from the corresponding encoding genes indicated that the
majority of the obtained clones were related to the known anammox bacteria
Candidatus "Brocadia," Candidatus "Kuenenia," and Candidatus "Scalindua." The
abundances of anammox bacteria were determined by quantitative PCR, and between
2.13 * 105 and 1.15 * 106 16S rRNA gene copies per gram of compost were found.
This study provides the first demonstration of the existence of anammox bacteria
with limited diversity in cow manure composting.
PMID- 28511296
TI - (E)-2-Methoxy-4-(3-(4-Methoxyphenyl)Prop-1-en-1-yl)Phenol Induces Apoptosis in
HeLa Cervical Cancer Cells via the Extrinsic Apoptotic Pathway.
AB - (E)-2-Methoxy-4-(3-(4-methoxyphenyl)prop-1-en-1-yl)phenol (MMPP), derived from
butenal, is a recently synthesized Maillard reaction product. Owing to its
novelty, little is known about the function of MMPP. In this study, we elucidated
the effects of MMPP on apoptosis in cervical cancer by using the HeLa cervical
cancer cell line, which is widely used in cancer research. We observed that MMPP
was cytotoxic to HeLa cells and induced activation of caspase-3, -8, and -9,
without affecting the expression of the viral oncogenes E6 and E7. In particular,
the expression of the death receptors DR5 and FAS was significantly increased by
MMPP treatment. There were no significant alterations of mitochondrial intrinsic
factors. Taking all these results together, our findings show that MMPP primarily
induces apoptosis in HeLa cervical cancer cells via the extrinsic apoptotic
signaling pathway, accompanied by an enhanced expression of death receptors.
PMID- 28511297
TI - [The effect of complement C3a receptor antagonist in the kidney immune injury in
trichloroethylene-sensitized mice].
AB - Objective: To explore the effect of complement C3 a-C3a receptor in the kidney
immune inju-ry in trichloroethylene-sensitized mice by using C3a receptor
specific antagonist C3aRA and discuss the patho-genesis of kidney injury in
occupational dermatitis medicamentosa-like of trichloroethylene (ODMLT) .
Methods: 42 female 6~8 weeks old BALB/c mice of specific pathogen free were
randomly divided into blank control group (5) , solvent control group (5) , TCE
treatment group (16) and TCE+C3aRA treatment group (16) . The TCE treat-ment
group and TCE+C3aRA treatment group were further divided into the sensitized
group and the non-sensi-tized group according to the skin sensitization test
score. Renal function was detected by biochemical detection kit; expression of
C3aR in kidney tissue was detected by qPCR; expression of IL-1beta and TNF-alpha
protein were de-tected by immunohistochemical. Results: Compared with solvent
control group and corresponding non-sensitized group, CRE and BUN in TCE
sensitized group and TCE + C3aRA sensitized group were significantly increased
(P<0.05) . Compared with TCE sensitized group, CRE and BUN in TCE+C3aRA
sensitized group were signifi-cantly decreased (P<0.05) . Compared with solvent
control group and TCE non-sensitized group, the expression level of C3aR gene in
kidney tissue in TCE sensitized group was significantly increased (P<0.05) .
There was a large number of IL-1beta and TNF-alpha protein expression in kidney
tissue in TCE sensitized group and TCE+C3aRA sensitized group. Compared with the
TCE sensitized group, the expression level of IL-1beta and TNF-alpha protein in
kidney tissue in TCE+C3aRA sensitized group was significantly decreased (P<0.05)
. Conclusion: C3a-C3aR may be involved in the kidney immune injury in TCE
sensitized mice, C3aRA has a protective effect on the kid-ney immune injury in
TCE sensitized mice.
PMID- 28511298
TI - [Influence of aluminum chloride exposure on embryonic development of zebrafish
and neurobehavior of juvenile fish].
AB - Objective: To investigate the influence of aluminum chloride (AlCl(3)) solution
on the embryon-ic development of zebrafish and neurobehavior of juvenile fish.
Methods: The embryos of zebrafishat 6 hours after fertilization were exposed to
AlCl(3) solution at a concentration of 0, 55.0, 60.5, 66.6, 73.5, 80.5, or 100.0
mg/L, and embryonic hatching rates at 48 and 72 hours after fertilization were
calculated. The embryos of zebrafishat 6 hours after fertilization were exposed
to AlCl(3) solution at a concentration of 0, 60.0, 72.0, 86.4, 103.7, or 124.4
mg/L, and the embryonic mortality rates at 12, 24, 48, 72, and 96 hours after
fertilization were calculat-ed. The embryos of zebrafish at 6 hours after
fertilization were exposed to AlCl(3) solution at a concentration of 0, 50, 100,
200, 400, or 800 MUg/L, and the changes in the neurobehavior of juvenile fish
were observed after hatching, including touch-escape reaction at 72 hours after
fertilization and autonomic movement and panic es-cape reflex at 7 days after
fertilization. Results: Compared with the 0 mg/L group, the>=66.6 mg/L group had
a sig-nificant reduction in embryonic hatching rate at 48 and 72 hours after
fertilization, and the >=72.0 mg/L group had a significant increase in embryonic
mortality rate at 96 hours after fertilization (P<0.05) . Compared with the 0
MUg/L group, the>=100 MUg/L group had a significant reduction in the number of
times of touch-escape reaction (P<0.05) .Compared with the 0 and 50 MUg/L groups,
the 100-800 MUg/L groups had significant reductions in total movement distance
and average speed (P<0.05) . Compared with the dark period before illumination,
all groups had a significant increase in movement speed during the light period
of the panic escape reflex test (i.e., the third minute) (P<0.05) ; within 2
minutes after the light was turned off, there was no significant change in
movement speed in the 0-200 MUg/L groups (P>0.05) ; the 400 and 800 MUg/L groups
had a significant increase in movement speed (P<0.05) . Conclusion: AlCl(3)
exposure may cause embryonic developmental disorder in zebrafish and ab-normal
neurobehavior in juvenile fish.
PMID- 28511299
TI - [Value of DNA content in comet tail in predicting changes in blood cell counts in
workers exposed to benzene].
AB - Objective: To investigate the value of DNA content in comet tail (TailDNA) in
predicting the changes in peripheral blood cell counts in workers exposed to
benzene. Methods: In 2011, cluster sampling was used to select 150 male workers
exposed to benzene in a petrochemical factory. Cubital venous blood and urine
samples were collected for routine blood rest, comet assay, and measurement of s
phenylmercapturic acid (SPMA) and urine creatinine. The population was divided
into groups according to urinary SPMA or TailDNA, and routine blood test results
within 3 years were collected to analyze the changes in blood cell counts.
Results: The low-SPMA group had significantly higher white blood cell and
neutrophilcounts in all years than the high-SPMA group (P<0.05) . The low-Tail
DNA group had a significant increase in platelet count from 2012 to 2014 (P<0.05)
, while the high-Tail DNA group had no significant change (P>0.05) . During the 4
year period, the high-TailDNA group had a significantly lower red blood cell
count than the low-TailDNA group (P<0.05) . The high-TailDNA group showed a
gradual reduction in white blood cell count over time (beta=-0.113, P<0.05) , and
the low-TailDNA group showed no trend of the reduction in white blood cell count
(P>0.05) . Conclusion: TailDNA can be used to predict the changes in blood cell
counts in workers exposed to benzene.
PMID- 28511300
TI - [Mediator effect analysis of the trait coping style on job stress and fatigue of
the military personnel stationed in plateau and high cold region].
AB - Objective: To investigate the fatigue status of military personnel stationed in
plateau and high cold region, and to analyze the mediator effect of trait coping
style on job stress and fatigue. Methods: In October 2010, with the method of
cluster random sampling survey, 531 military personnel stationed in plateau and
high cold region were chosen as subject. The fatigue status were evaluated by the
Chinese version multidimensional fatigue inventory (MFI-20) , job stress were
evaluated by the Job Stress Survey (JSS) , and trait coping style were evaluated
by the Trait Coping Style Questionnaire (TCSQ) . Results: According to the
information of different population characteristics, mean rank of physical
fatigue about the urban (town) group were higher than that of rural group (Z=
2.200, P<0.05) ; mean rank of reduced motivation about the urban (town) group
were higher than that of rural group (Z=-2.781, P<0.05) ; mean rank of general
fatigue scores about the urban (town) group were higher than that of rural group
(Z=-3.026, P<0.05) ; mean rank of physical fatigue about the up or equal 20-years
old age group were higher than that of below 20-years old age group (Z=-4.045,
P<0.05) ; mean rank of reduced motivation about the up or equal 20-years old age
group were higher than that of below 20-years old age group (Z=-2.182, P<0.05) ;
mean rank of mental fatigue about the up or equal 20-years old age group were
higher than that of below 20-years old age group (Z=-2.879, P<0.05) ; mean rank
of general fatigue scores about the up or equal 20-years old age group were
higher than that of below 20-years old age group (Z=-3.647, P<0.05) ; mean rank
of reduced motivation were significant statistical difference among the military
officers, sergeancy and soldier group (F=18.965, P<0.05) ; mean rank of general
fatigue scores were significant statistical difference among the military
officers, sergeancy and soldier group (F=14.711, P<0.05) . The score of negative
coping style were positively correlated with the score of physical fatigue
(r(s)=0.129) , reduced activity (r(s)=0.123) , reduced motivation (r(s)=0.149)
and general fatigue (r(s)=0.174) respectively, the score of organizational
support lack strength were positively correlated with the score of physical
fatigue (r(s)=0.090) , reduced activity (r(s)=0.098) , reduced motivation
(r(s)=0.099) and general fatigue (r(s)=0.130) respectively. The mediator effect
of negative coping style on the job stress and fatigue was 0.013 (P<0.01) .
Conclusion: The fatigue statuses of the urban (town) group and the up or equal 20
years old age group are poor, and the negative coping style plays mediator effect
on the job stress and fatigue.
PMID- 28511301
TI - [Mediating role of over-commitment in the relationship between effort, reward and
burnout].
AB - Objective: To explore the mediating role of over-commitment in the relationship
between occupational stressors and job burnout, and to offer more
specificevidence-based information in exploring the work related health effects
of over-commitment. Methods: A total of 1994 samples from electronic
manufacturing service industry were collected in Guangdong province based on self
rated questionnaire after written consent from June to July, 2015. The Effort
Reward Imbalance questionnaire and Maslach Burnout Invertory-General Survey were
used for the measurement of occupational stress and job burnout. And hierarchical
regression and Bootstrap test were conducted for data analysis. Results: High
effort (0.28, 0.24-0.33) and low reward (-0.37, -0.42--0.33) were significantly
associated with high over-commitment when gender, age and position had been
controlled. Standardizedregression coefficient of effort to emotional exhaustion,
depersonalization and personal accomplishment were 0.63 (95%CI: 0.54-0.71) ,0.18
(95%CI: 0.10-0.26) ,0.32 (95%CI: 0.21-0.43) , P<0.05; and standardized regression
coefficient of reward to emotional exhaustion, depersonalization and personal
accomplishment were-0.60 (95%CI: -0.68--0.52) ,-0.93 (95%CI: -1.01--0.86) ,-0.46
(95%CI: -0.35--0.58) , P<0.05. Bootstrap test indicated the mediation of over
commitment were statistically significant, and mediating effect ranges from 0.093
to 0.218 (P<0.05) . Conclusion: Over-commitment can mediate the relationship
between occupational stressors (job effort and reward) and burnout, and the
effect varies from different workingconditions.
PMID- 28511302
TI - [Epidemiological and occupational characteristics of occupational chemical
poisoning in Tianjin city during 2006-2015].
AB - Objective: To provide scientific evidence for the prevention and control measures
of acute and chronic occupational poisoning by analyzing the epidemiological and
occupational characteristics of occupational chemical poisoning cases reported in
Tianjin city during 2006-2015. Methods: In September 2016, based on the China
Disease Control and Prevention Information System, a database of occupational
poisoning cases in Tianjin from 2006 to 2015 was established. The epidemiological
characteristics of occupational poisoning were analyzed including three
distributions firstly, and then the occupational characteristics were analyzed
such as length of service, industry distribution and source of poison. Results:
There were 174 occupational poisoning patients in Tianjin from 2006 to 2015,
including 16 cases of acute poisoning (9.20%) and 158 cases of chronic poisoning
(90.8%) , and the proportion of occupational poisoning cases reported in Binhai
New Area is the highest. The number of reported cases of chronic occupational
poisoning shows a downward trend. Occupational poisoning cases are concentrated
mainly in the age of 40-60 years and length of service of 10-20 years. The high
incidence of occupational poisoning mainly exists in the chemical raw materials
and chemical manufacturing industry and general, professional equipment
manufacturing industry. Acute poisoning was mainly by asphyxial gas (50.00%) ,
and chronic poisoning was mainly by organic solvent (43.67%) . Conclusion: The
distribution of occupational poisoning cases in diverse toxic types and regions
in Tianjin are quite different. The occupational safety precautions of the
chemical raw materials and chemical products manufacturing and occupational
poisoning control work in Binhai new area should be strengthened to reduce the
occurrence of occupational poisoning.
PMID- 28511303
TI - [Association of XRCC1 gene polymorphism and low dose ionizing radiation with
peripheral blood lymphocyte micronucleus].
AB - Objective: To explore the effects of X-ray repair cross complementing gene 1
(XRCC1) polymorphism and low dose ionizing radiation exposure on radiology
professionals' peripheral blood lymphocyte micronucleus. Methods: A matched case
control study was designed. From 2013 to 2015, 1 102 radiology professionals with
micronucleus test rusults, and 45 cases with present micronucleus were enroled
into case group. 180 diagnostic radiology technicians detecting no micronucleus
were chosen as control group, cases and controls were 1?4 mached on gender, age
<=40 or >40 years old. According to the detection of micronucleus levels (00/00,
10/00, 20/00) , the objects of our study were divided into the reference group,
the low detection group and the medium detection group. The form of radiation
workers' occupational health examination was used to collect the general baseline
of the research objects, history of smoking, drinking, poisonous and harmful
material exposure, past medical history, accumulated illuminated dose and
lymphocyte micronucleus rates (0/00) , etc. Using restriction fragment length
polymorphism polymerase chain reaction (RFLP-PCR) technology for genotyping;
Compared the baseline data and radiation exposure level between the
differentmicrokernel detection groups; Adopted multivariate logistic regression
to analysis the combination effect of XRCC1 Arg399Gln gene polymorphism and
accumulated illuminated dosefor micronucleus rate. Results: The accumulated
illuminated dose in the reference group, the low detection group and the medium
detection group were (23.44+/-15.23) , (21.76+/-2.56) , (24.22+/-18.61) mSv,
respectively. There was no statistically significant difference among the groups
(P>0.05) . Under the dominant inheritance mode, after adjusted age, smoking and
drinking factors, the results suggested that XRCC1 Arg399Gln micronucleus medium
detection group compared with the reference group, Arg399Gln-GG as reference,
Arg399Gln-GA+AA decreased the occurrence of micronucleus (OR=0.175, 95%CI: 0.036
0.848) . Arg194Trp and Arg280His did not affect the incidence of micronucleus
(P>0.05) . Did not find the combination effect of XRCC1 Arg399Gln gene
polymorphism and accumulated illuminated dose for micronucleus rate (P>0.05) .
Conclusion:XRCC1 Arg399Gln gene polymorphism can affect the incidence of
micronucleus, and carrying the XRCC1 Arg399Gln-GA+AA genotype is a protective
factor of micronucleus's occurrence, but low dose ionizing radiation may not
affect the occurrence of micronucleus independently.
PMID- 28511304
TI - [Impact of carbon dioxide pneumoperitoneum in operating rooms on the health of
medical staffs].
AB - Objective: To evaluate the impact of CO(2) pneumoperitoneum in operating rooms on
the health of medical staffs. Methods: In June 2016, the thirty-three medical
staffs in operating rooms were chosen as the object of the research.Seventeen
people who took part in the pneumoperitoneum operation were selected as a
exposure group and sixteen people who took part in the laparotomy operation were
selected as a control group.Vital signs and arterial blood gases of medical
staffs in the two groups were both measured in pre-operation and post-operation.
Occupational Health Questionnaires were conducted to collect information on age,
weight and postoperative symptoms. The level of CO(2) in operating room was
determined by a portable infrared CO(2) analyzer. Results: Compared with the
control group, the concentration of CO(2) in the exposed group was higherat T(1),
T(2) and T(3) (t=22.227, 13.583, 17.408, P<0.05) . Heart rates and PaCO(2) in the
exposure group raised greatly (t=2.132, 2.129, P<0.05) , while pH decreased (t=
3.015, P<0.05) . The differences between the two groups were statistically
significant. Conclusion: The increase of mild acidosis and thesense of job
burnout in medical staffs could be caused by CO(2) pollution in the operating
rooms.
PMID- 28511305
TI - [Value of heart rate as an optimum index in evaluating physical labor intensity].
AB - Objective: To investigate the possibility of heart rate as an optimum index for
evaluating physical labor intensity. Methods: From September to October, 2015, a
total of 111 male young adults were selected as study subjects. A cycle ergometer
was used for exercise at different intensities (20, 40, 60, 80, 100, 120, 140,
160, and 180 W) , and the exercise at each intensity lasted for 6 minutes. The
subjects wore the K4b2 portable cardiopulmonary function testing instrument for
the real-time monitoring of heart rate (HR) , pulmonary ventilation volume (Ve) ,
oxygen consumption (VO(2)) , and energy metabolic rate (E) . The origin software
was used for correlation and regression analyses of HR, Ve, VO(2), and E
collected at different intensities to establish Ve-HR, VO(2)-HR, and E-HR
regression equations. Results: At different intensities, HR was positively
correlated with Ve, VO(2), and E (r=0.8985, 0.8733, and 0.8973, all P<0.01) .
There was a significant difference in the R(2) value of Ve-HR, VO(2)-HR, and E-HR
regression equations (R(2)=0.8070, 0.7625, and 0.8049, all P <0.01) . The
validation results showed that there was no significant difference between the
calculated values and the measured ones (P>0.05) . Conclusion: HR can replace Ve,
VO(2), and E and be used as an optimum index for evaluating physical labor
intensity.
PMID- 28511306
TI - [Relationship of job stress with job burnout and quality of work life in workers
for offshore oil platforms].
AB - Objective: To evaluate the current status of job burnout and qual ity of work
life (QWL) in workers for offshore oil platforms, and to analyze the relationship
of job stress with job burnout and QWL and the direct and indirect effects of job
stress on QWL. Methods: Cluster random sampling was used to select 382 work-ers
for 8 oil platforms of China National Offshore Oil Corporation in October 2015. A
self-designed questionnaire was used to collect the individual characteristics of
subjects. The Quality of Work Life Scale (QWL7-32) , Occupa-tional Stress
Inventory-Revised Edition (OSI-R) , and Maslach Burnout Inventory-General Survey
(MBI-GS) were used to investigate the QWL, job stress, and job burnout of
subjects. Results: Among all the workers for offshore oil platforms, 87.2% had
mild job burnout. The total QWL score was 116.01 +/- 16.73; 8.3% of the workers
had poor QWL, and 68.5% had moderate QWL. QWL was reduced with heavier task,
vaguer task, and increasing mental stress and physical stress (P<0.05) , and
increased with more social support (P<0.05) . Job stress had di-rect and indirect
effects on QWL; stress reaction had the most effect on QWL (total effect size
0.509) , followed by social support (total effect size 0.444) . Conclusion: Most
workers for offshore oil platforms have mild job burn-out and moderate QWL. Job
stress is associated with job burnout and QWL, and stress reaction and social
support have relatively high influence on QWL.
PMID- 28511307
TI - [Influence of long-time video operation on hemodynamics of the retrobulbar
arteries in operators].
AB - Objective: To investigate the influence of long-time video operation on
hemodynamics of the retrobulbar arteries in operators. Methods: From March to
October, 2015, a total of 120 soldiers for office work engaged in video
surveillance were enrolled as study group, and 155 fire fighters were enrolled as
control group. The incidence of eye discomfort was compared between the two
groups. Color Doppler ultrasound was used to measure and compare the peak
systolic velocity (PSV) , end-diastolic velocity (EDV) , and resistance index
(RI) of the central retinal artery (CRA) and the short posterior ciliary artery
(SPCA) , and the correlation of video operation time with the hemodynamic
parameters of the retrobulbar arteries was analyzed. Results: The study group had
a significantly higher incidence rate of eye discomfort than the control group
(P<0.05) . Compared with the control group, the study group had significant
reductions in the PSV and EDV of the CRA and the SPCA and a significant increase
in the RI of the CRA (P<0.05) . Video operation time was negatively correlated
with the PSV and EDV of the CRA and the SPCA (r=-0.61, -0.54, -0.65, and-0.68,
all P<0.05) and positively correlated with the RI of the CRA and the SPCA (r=0.56
and 0.63, P<0.05) . Conclusion: Long-time video operation can increase the
incidence of eye discomfort and lead to increased blood resistance of the CRA and
the SPCA and reduced retinal perfusion.
PMID- 28511308
TI - [Blood-borne occupational exposure and protection in medical staff of a
traditional Chinese medicine hospital].
AB - Objective: To investigate blood-borne occupational exposure and related
protection in the medical staff of a traditional Chinese medicine hospital, and
to provide a reference for reducing the risk of blood-borne occupational
exposure. Methods: Forty-eight medical workers with blood-borne occupational
exposure in 2015 were selected to analyze the incidence of blood-borne
occupational exposure, influencing factors, operations that caused blood-borne
occupational exposure, pathogens, and occupational protection. Results: The
incidence rate of blood-borne occupational exposure in the medical staff of the
traditional Chinese medicine hospital in 2015 was 3.30% (48/1 455) , and the
frequency was 0.04 time/person/year. The workers with blood-borne occupational
exposure were mostly nurses, females, workers aged <30 years, workers with <5
working years, and workers with a junior professional title. There was a
significant difference in the incidence rate of blood-borne occupational exposure
between workers with different ages and working years. The main way of blood
borne occupational exposure was sharp injury (96.08%) . The main operations that
caused blood-borne occupational exposure were covering or separating the syringe
needle after injection and disposing used sharp instruments. The main exposure
site was the hand (96.08%) , with the thumb and index finger for the left hand
and the middle finger and index finger for the right hand; there was no
significant difference in the exposure site distribution between the two hands
(P<0.05) . The main pathogen that caused blood-borne occupational exposure was
hepatitis B virus (68.96%) . The rate of correct local treatment for blood-borne
occupational exposure was 88.24%. The rate of prophylactic medication was 74.51%,
and hepatitis B immunoglobulin (HBIG) plus hepatitis B vaccine was the main way,
followed by HBIG. In all workers with blood-borne occupational exposure, 62.74%
did not wear gloves. Conclusion: The medical workers with few working years have
a high risk of blood-borne occupational exposure, so the training on protection
against blood-borne occupational exposure should be strengthened to reduce the
risk of blood-borne occupational exposure and infection.
PMID- 28511310
TI - [Report of 6 cases of malignant arrhythmia induced by acute poisoning].
PMID- 28511309
TI - [Effect of occupational exposure on job burnout in nurses].
AB - Objective: To investigate the effect of occupational exposure on job burnout in
nurses, and to analyze the mediating effect of negative emotion between
occupational exposure and job burnout and the regulatory effect of supervisor
support on occupational exposure and negative emotion. Methods: From September to
December, 2015, simple random sampling was used to select 543 nurses from six
tertiary hospitals in Zhejiang Province, China. The questionnaires consisted of
occupational exposure risk questionnaire, negative emotion questionnaire,
supervisor support questionnaire, and job burnout questionnaire. Results: The
total score of occupational exposure risk in nurses was 11.43+/-7.19; the score
of emotional exhaustion was 3.19+/-1.24, the score of low sense of personal
accomplishment was 3.02+/-1.21, and the score of sense of working indifference
was 2.24+/-1.06. There were significant differences in occupational exposure
score between nurses with different sexes (t=2.61, P<0.01) and working years
(F=4.49, P<0.01) . There were significant differences in the scores of emotional
exhaustion and low sense of personal accomplishment in nurses with different
sexes (t=5.25, P<0.001) and working years (t=-3.48, P<0.01) . Occupational
exposure had positive effects on negative emotion (beta=0.41, P<0.05) , emotional
exhaustion (beta=0.47, P<0.05) , sense of working indifference (beta=0.42,
P<0.05) , and low sense of personal accomplishment (beta=0.17, P<0.05) . Negative
emotion had a partial mediating effect between occupational exposure and
emotional exhaustion (total effect size 30.5%, P<0.05) and between occupational
exposure and sense of working indifference (total effect size 37.1%, P<0.05) .
Negative emotion had a complete mediating effect between occupational exposure
and low sense of personal accomplishment (beta=0.08, P>0.05) . Supervisor support
negatively regulate the effects of occupational exposure and negative emotion
(F=21.73, P<0.001) . Conclusion: In nurses, occupational exposure has a direct
positive effect on job burnout and indirectly influences job burnout via negative
emotion. Supervisor support can reduce the negative impact of occupational
exposure on negative emotion.
PMID- 28511311
TI - [Analysis of misdiagnosis of common occupational toxic abdominal pain].
PMID- 28511312
TI - [Size exclusionchromatography-high-performance liquid chromatography-inductively
coupled plasma mass spectrometry for measuring the stability of cadmium
telluridequantum dots].
AB - Objective: To investigate the peak time and peak area of elements in cadmium
telluride quantum dots (CdTe QDs) using size exclusion chromatography-high
performance liquid chromatography-inductively coupled plasma mass spectrometry,
as well as the biological stability of CdTe QDs in vivo and in vitro. Methods:
Transmission electron microscope and ultraviolet fluorescence were used for
characterization and synthesis of water-soluble CdTe QDs, and CdTe QDs were added
to double-distilled water, mobile phase, or bovine serum medium to observe the
change in stability after different periods of time. CdTe QDs were injected into
the vein of mice, and the changes in the morphology of CdTe QDs in serum and the
liver were measured at 1, 24, and 72 hours after exposure. Size exclusion
chromatography-high-performance liquid chromatography was used for the elution of
the compounds in the solution based on their volume, and then inductively coupled
plasma mass spectrometry was performed for the eluent. The flow time of (114)Cd
and (130)Te and molar ratio were used for qualitative analysis of CdTe QDs, and
the peak area was used to judge whether CdTe QDs were degraded. Results: CdTe QDs
were diluted to a concentration of 0.5 mmol/L with double-distilled water and
then placed in a dark place at room temperature; CdTe QDs were completely
degraded after 60 minutes. CdTe QDs were diluted to a concentration of 0.005
mmol/L with a mobile phase, and the peak of CdTe QDs was not detected. After CdTe
QDs were placed in a dark place at room temperature for 48 hours at a
concentration of 0.005 mmol/L in bovine serum mediumin vitro, the peak area of
(114)Cd was 6179841-7346084, and the peak area of (130)Te was 1077913-1191066.
CdTe QDs had the highest peak area at 1 hour after exposure, and the peak areas
of (114)Cd and (130)Te were 18183894 and 25187987, respectively. CdTe QDs were
quickly degraded in the liver; at 1 hour after exposure, the degradation products
of CdTe QDs containing Cd were observed in liver tissue homogenate, and CdTe QDs
were largely degradedat 24 hours. Conclusion: This method can be used to
investigate the biological stability of CdTe QDs. CdTe QDs are degraded in the
liver and produce Cd(2+), which may cause toxic reaction.
PMID- 28511313
TI - [Determination of thiocyanate within human urine by ion chromatography method].
AB - Objective: To establish ion chromatography method to determine thiocyanate within
urine of workers who were exposed to cyanide. Methods: After the workers work,
used 50 ml centrifuge tube to collect the urine of workers about 20 ml.The urine
were tested by centrifugation, dilution and filtration by C(18) column,
thiocyanate was separated by AS(16) and mobile phase elution by KOH, detected by
electrical circuitryconductivity detector, quantitative by the standard curve
method. Results: The linear correlation coefficient of thiocyanate within the
range of 0.1-5.0 MUg/ml was more than 0.999. The method detection limit was
0.11MUg/ml (in 1ml urine) , the method quantitative limit was 0.35 MUg/ml. The
method recoveries were 95.1%-99.7%. The within-day precision range was 0.54%
2.05%, The between-run precision range was 2.06%-5.09%. Sample stability test
showed that thiocyanate samples could be stored for 5 days at room temperature
and 7 days at 4 C, could be stored for 14 days at-20 C. Conclusion: The technical
indicator of method compliance with rule of Guide for establishing occupation
health standards-Part 5: determination methods of chemicals in biological
materials (GBZ/T 210.5-2008) , the method applies to workers who were exposed to
cyanide.
PMID- 28511314
TI - [Determination of cadmium in human urine by colloidal gold immunochromatographic
assay].
AB - Objective: To establish the method of colloidal gold immunochrom atographic assay
for detecting cadmium ions rapidly. Methods: The anti-cadmium ion monoclonal
antibody-gold conjugate was labeled on the binding pad, cadmium ion hapten and
goat anti-mouse IgG were coated on nitrocellulose membrane as the detection line
(T line) and quality control line (C line) respectively. The sample pad,
colloidal gold bonding pad, nitrocellulose membrane and absorption pad were
orderly assembled on the PVC board to cut into a test paper strip. The
qualitative results of the assay were visualized in color. Results: When
detecting the human urine cadmium ions, the results were tested qualitativly
within 15 minutes. The detection limit was 30 MUg/L. No cross-reactivity with
other heavy metal ions. The test paper strip could be stored at 4 C for 3 months.
Conclusion: The method has the advantages of low cost, strong specificity, good
stability and reliable results, and is suitable for rapid screening of cadmium
poisoning of enterprise and occupational health.
PMID- 28511315
TI - [A cost-benefit analysis of occupational disease reporting in China].
AB - Objective: To perform a cost-benefit analysis of the occupational disease
reporting system in China, and to provide a basis for effective resource
allocation. Methods: The data on the cost of occupational diseases were collected
from China Health Statistics Yearbook 2013, the estimated benefit data were
collected from published articles in China and foreign countries, and the
probability data were collected from the occupational diseasereports published by
health and family planning administrative departments. Adecision-making tree was
used for the cost-benefit analysis. Results: The estimated cost of occupational
disease reporting was about 102.47 million yuan/year, consisting of a cost of
reporting in national medical institutions of 1.25 million yuan/year, a
management cost of 30.35 million yuan/year, a management cost in local public
health institutions of 69.80 million yuan/year, a management cost in national
public health institutions of 370 thousand yuan/year, and a cost of construction
and maintenance of reporting system of 700 thousand yuan/year. The results of the
decision tree analysis showed that when an occupational disease monitoring system
was established, the incremental input for occupational disease monitoring and
prevention/control was 2.1 billion yuan/year, the output was 6.5 billion
yuan/year, and the benefit of occupational disease reporting system was 4.4
billion yuan/year. Conclusion: The benefit of occupational disease reporting
system depends on the cost-benefit of occupational disease prevention and control
measures, and proper prevention and control measures are extremely important for
improving the benefit of occupational disease reporting system.
PMID- 28511316
TI - [Research progress on Lgr5 protein].
PMID- 28511317
TI - [Research progress on the p-phenylenedinamine toxicity and effect on health].
PMID- 28511318
TI - [research progress on biomarkers of diphenylmethane diisocyanate].
PMID- 28511319
TI - [Status of diagnosis and treatment of non-ST-segment elevation acute coronary
syndrome in China].
PMID- 28511320
TI - [Guideline and consensus for the management of patients with non-ST-elevation
acute coronary syndrome(2016)].
PMID- 28511321
TI - [Impact of CYP2C19 genotype and platelet function on clinical outcome in coronary
atherosclerotic heart diseases patients received clopidogrel post percutaneous
coronary intervention].
AB - Objective: To analyze association of CYP2C19 genotype and platelet function
phenotype and their impact on clinical outcomes including bleeding events of
coronary artery disease(CAD) patients received clopidogrel post percutaneous
coronary intervention(PCI). Methods: Coronary atherosclerotic heart diseases
patients underwent elective PCI and coronary stent implantation in Fuwai hospital
were prospectively enrolled during May 2012 to April 2013. Patients were assigned
into groups by genotype of CYP2C19 (extensive metabolizers, intermediate
metabolizers, and poor metabolizers) and phenotype of platelet function
(clopidogrel responders, semi-responders, and non-responders). The rates of major
adverse cardiovascular events, combined cardiovascular events, and bleeding
events were recorded during a at least 12 months follow-up period and compared
among above defined groups. The association between genotype or phenotype and
clinical outcome was assessed using multivariable Cox regression hazards model.
Results: Three hundred and eighty patients received coronary stent implantation
and met the inclusion criteria of the study, including 157(41.3%) clopidogrel
extensive metabolizers, 176(46.3%) intermediate metabolizers, and 47(12.4%) poor
metabolizers according to the genotype grouping; 98(25.8%) were responders to
clopidogrel, 149(39.2%) were semi-responders, and 133 (35.0%) were non-responders
according to the phenotype grouping. Three hundred and seventy-six patients
accomplished follow-up. The highest combined cardiovascular events rate was
observed in the poor metabolizers (34.0%(16/47)) as compared to the intermediate
metabolizers (19.0%(33/174), P=0.026) and the extensive metabolizers
(15.5%(24/155), P=0.005). The highest bleeding events rate was observed in the
clopidogrel responders (33.7%(33/98)) as compared to the semi-responders
(18.9%(28/149), P=0.008) and non-responders (17.7%(23/130), P=0.008). In
multivariable Cox regression analysis, the adjusted risk of cardiovascular death,
acute myocardial infarction, stent embolism, target lesion revascularization and
angina onset was 2.305 times higher in clopidogrel poor metabolizers than in
extensive and semi-metabolizers (95%CI=1.208-4.399, P=0.011). The adjusted HR for
bleeding events was 0.540 (95%CI=0.321-0.909, P=0.021) among semi-responders vs.
responders, was 0.52 (95%CI=0.301-0.905, P=0.021) among non-responders vs.
responders during the 12 months follow-up period. Conclusions: Among CAD patients
underwent stenting and clopidogrel treatment, poor CYP2C19 metabolizers group
carries a significantly higher risk for combined cardiovascular events than in
extensive metabolizers group, while clopidogrel responders patients are at
significantly higher risk for bleeding as compared to the semi-responders and non
responders.
PMID- 28511322
TI - [Interaction between APOB gene polymorphism and risk factors in coronary heart
disease patients without lipid-lowering treatment].
AB - Objective: To investigate the association between APOB gene R532W polymorphism
and the risk of coronary heart disease (CHD) in patients without lipid-lowering
treatment and to analyze the interactions between the variation of R532W and
different risk factors of CHD. Methods: CHD and non-CHD were diagnosed according
to coronary artery angiography (CAG) and/or coronary computed tomography
angiogram (CTA) results, as well as clinical features. Blood samples from 771 CHD
patients and 772 age- and sex-matched non-CHD controls, who never accepted any
lipid-lowering treatments, were collected. R532W was genotyped by HumanExome
BeadChip at BGI and strict quality control was made. Firstly, the association
between R532W polymorphism and the risk of CHD in 3 genetic models (GA+ AA vs.GG,
AA vs. GG+ GA, AA vs. GA vs. GG) after adjusting confounding factors was
explored. Then, the interactions between the variation of this loci and risk
factors related to CHD were investigated. Results: (1) Total cholesterol (TC)
levels were significantly lower in AA genotype than in GA genotype in the total
cohort and non-CHD controls, but was similar among the 3 genotypes in CHD
patients. (2) R532W GG, GA and AA distribution was 80.7%, 18.2% and 1.2% in CHD
patients, and 74.6%, 23.8% and 1.6% in non-CHD controls (P<0.05). (3) R532
polymorphism was related to the incidence of CHD in the dominant model, and A
allele carriers were related to about 35% reduced risk of CHD (OR=0.653, 95% CI
0.502-0.849, P=0.001) after adjusting for confounding factors. (4) R532W
polymorphism had positive interactions with hypertension (1.452) and smoke
(1.077), while negative interaction with diabetes (0.553) in the occurrence of
CHD. Conclusions: APOB gene R532W polymorphism is related to TC levels in Chinese
north Han population. A-allele carries of R532W loci is linked with reduced risk
of CHD in the absence of lipid-lowering treatment. R532W polymorphism has a
positive additive interaction with hypertension and smoke, while a negative
additive interaction with diabetes mellitus in the occurrence of CHD.
PMID- 28511323
TI - [Impact of symptom onset to first medical contact time on the prognosis of
patients with acute ST-segment elevation myocardial infarction].
AB - Objective: To investigate the impact of symptom onset to first medical contact
(SO-to-FMC)time on the prognosis of patients with acute ST-segment elevation
myocardial infarction(STEMI). Methods: The clinical data of 341 consecutive STEMI
patients, who were hospitalized to our hospital and received primary percutaneous
coronary intervention(PCI) from August 2011 to April 2016, were retrospectively
analyzed. The patients were divided into <=90 min group (201 cases) and >90 min
group (140 cases) according to the SO-to-FMC time. The treatment time, mortality
and incidence of major adverse cardiac and cerebro-vascular events(MACCE) were
analyzed. The risk factor of 1-year mortality after PCI and 1-year incidence of
MACCE during the post-discharge follow-up period were analyzed by binary logistic
regression analysis. The predictor of 4.5-year mortality after PCI was analyzed
by multivariate Cox regression analysis. Methods The door to balloon time
(104(88, 125) min vs. 111(92, 144)min, P=0.023), first medical contact to balloon
time(146(119, 197) min vs. 177(125, 237)min, P=0.005), and symptom onset-to
balloon time(200(170, 257) min vs. 338(270, 474)min, P<0.001)were all
significantly shorter in the <=90 min group than in>90 min group. The 30-day
mortality (2.99% (6/201) vs. 7.86%(11/140), P=0.042), 1-year mortality (2.89
(5/173) vs. 9.57(11/115), P=0.015), 1-year incidence of MACCE during the post
discharge follow-up period(1.16%(2/173) vs. 6.96%(8/115), P=0.021), and 4.5-year
cumulative mortality(3.00% vs. 11.20%, P=0.007) after PCI were significantly
lower in the <=90 min group than in the >90 min group. Moreover, the 4.5-year
incidence with free of MACCE (97.20% vs. 88.80%, P=0.025) during the post
discharge follow-up period was significantly higher in the <=90 min group than in
the >90 min group. In-hospital mortality was similar between the two groups
(2.49%(5/201) vs. 6.43%(9/140), P=0.071). Results: The door to balloon time
(104(88, 125) min vs. 111(92, 144)min, P=0.023) , first medical contact to
balloon time(146(119, 197) min vs. 177(125, 237)min, P=0.005), and symptom onset
to-balloon time(200(170, 257) min vs. 338(270, 474)min, P<0.001) were all
significantly shorter in the <=90 min group than in >90 min group. The 30-day
mortality(2.99% (6/201) vs. 7.86%(11/140), P=0.042), 1-year mortality
(2.89(5/173) vs. 9.57(11/115), P=0.015), 1-year incidence of MACCE during the
post-discharge follow-up period (1.16%(2/173) vs. 6.96%(8/115), P=0.021), and 4.5
year cumulative mortality (3.00% vs. 11.20%, P=0.007) after PCI were
significantly lower in the <=90 min group than in the >90 min group. Moreover,
the 4.5-year incidence with free of MACCE (97.20% vs. 88.80%, P=0.025) during the
post-discharge follow-up period was significantly higher in the <=90 min group
than in the >90 min group. In-hospital mortality was similar between the two
groups (2.49%(5/201) vs. 6.43%(9/140), P=0.071). Results of binary logistic
regression analysis showed that the SO-to-FMC time >90 min was the risk factor of
1-year mortality(OR=2.90, 95%CI 1.22-6.92, P=0.016) and 1-year incidence of MACCE
(OR=5.19, 95%CI 1.21-22.20, P=0.026) during the post-discharge follow-up period.
Multivariate Cox regression analysis demonstrated that the SO-to-FMC time >90 min
was the risk factor of 4.5-year mortality after PCI in patients with STEMI
(HR=2.88, 95%CI 1.10-7.53, P=0.031). Conclusion: Shorting the SO-to-FMC time can
significantly reduce the treatment time of STEMI patients, short and long-term
mortalities and the incidence of MACCE, and improve the prognosis of patients
with STEMI.
PMID- 28511324
TI - [Social support status and related influential factors of patients with acute
coronary syndrome].
AB - Objectives: To investigate the social support status, related influential factors
and the impact on one year outcome in patients with acute coronary syndrome
(ACS), our data might be helpful to provide basis for making new treatment
strategy aimed at improving social support for patients with ACS. Methods: From
January 2013 to June 2014, a total of 778 hospitalized patients with ACS were
enrolled in the study. All patients completed enhancing recovery in coronary
heart disease patients social support inventory(ESSI), general anxiety disorder
scale(GAD-7), patient health questionnaire(PHQ-9), short-form 12 health survey
questionnaire(SF-12), sleep questionnaire and demographic questionnaire within 7
days after admission and at 6 months and one year post discharge. Multiple linear
regressions were performed to analyze factors that influenced the social support.
Results: The total score of social support was 17.08+/-3.61, 17.72+/-3.04, and
17.76+/-3.05 respectively in patients with ACS at baseline, 6 months and 12
months after discharge. Patients had a higher point of social support at 6 months
(t=-2.69, P<0.01) and 12 months (t=-2.86, P<0.01) after discharge than at
baseline. Multiple regression analysis for baseline data identified five
significant predictors of low social support status: workers or farmers (t=2.82,
P<0.01), low family monthly income (t=2.42, P<0.05), anxiety (t=-3.66, P<0.01),
depression (t=-3.22, P<0.01) and low quality of life (t=4.38, P<0.01).
Conclusions: Social support of patients with ACS is lower in China, and there are
significant relationships between low social support and occupation, economic
status, anxiety, depression, quality of life of ACS patients.
PMID- 28511325
TI - [Feasibility of the 2014 European guidelines risk prediction model for sudden
cardiac death in hypertrophic cardiomyopathy in Chinese patients].
AB - Objective: Exploring the feasibility of the 2014 European Society of
Cardiology(ESC)guideline's risk prediction model for sudden cardiac death in
hypertrophic cardiomyopathy (HCM Risk-SCD) in Chinese patients. Methods: The
study population consisted of a consecutive cohort of 172 Chinese patients with
HCM without prior sudden cardiac death (SCD) event who were in patients in
Nanjing Drum Tower Hospital from December 2010 to October 2015.The endpoint event
was a composite of SCD and appropriate implantable cardioverter-defibrillator
(ICD) therapy.Clinical data were collected to calculate the 5-year SCD risk using
the HCM Risk-SCD formula and to observe the actual risk during the follow
up.Receiver operating characteristic curves (ROC) and the area under curve (AUC)
were calculated for the HCM Risk-SCD and risk stratification methods of the 2011
American Heart Association (AHA) guideline. Results: During follow-up of (2.69+/
1.36) years, five patients achieved the endpoint event.The predicated rate of SCD
event using HCM Risk-SCD was (2.36+/-1.73)%, (1.93+/-0.78)%, (5.18+/-0.65)%,
(8.77+/-2.38)% for all patients, low-risk group, medium-risk group and high-risk
group respectively.However, the actual rate of SCD event was 2.91%, 1.27%, 25.00%
and 14.29%, respectively.The AUC of 2014 ESC guideline and 2011 AHA guidelinewas
0.93(95%CI 0.85-1.00) vs. 0.87(95%CI 0.75-0.98). Conclusion: The predicated rate
of SCD event calculated by HCM Risk-SCD is lower than actual rate of SCD, but the
prediction efficiency and indication for ICD implantation of HCM Risk-SCD are
better than that of 2011 AHA guideline.
PMID- 28511326
TI - [Comparison of aortic annular diameter defined by different measurement
mordalities before transcatheter aortic valve implantation].
AB - Objective: To compare aortic annular diameter measured by transthoracic
echocardiography (TTE), transesophageal echocardiography (TEE), and multislice
computed tomography (MSCT) in patients with severe aortic stenosis, and to
evaluate the impact on selection of prosthetic valve type in transcatheter aortic
valve implantation (TAVI). Methods: Clinical data of 138 patients with severe
aortic stenosis referred for TAVI between January 2014 and June 2016 in our
hospital were retrospectively analyzed.The difference of aortic annular diameter
measured by TTE, TEE, and MSCT were compared.TTE was performed after TAVI to
evaluate the accuracy of measurement before TAVI. Results: (1) Aortic annular
diameter was (23.37+/-2.22) mm by TTE and (23.52+/-1.70) mm by TEE (P=0.12).
Pearson correlation analysis showed that aortic annular diameter measured by TTE
was correlated to that measured by TEE (r=0.87, P<0.05). (2)The long-axis
diameter and the short-axis diameter measured by MSCT multiplanar reconstruction
were significantly different ((27.86+/-2.87) mm vs. (21.91+/-2.53) mm, P<0.05).
There was no significant difference between the mean of the long- and short-axis
diameters and the diameter derived from cross-sectional area by MSCT ((24.92+/
2.38) mm vs. (24.84+/-2.25) mm, P=0.08). However, the diameter derived from the
circumference ((25.35+/-2.34) mm) was significantly larger than the mean of the
long- and short-axis diameters and the diameter derived from cross-sectional area
by MSCT, and the difference were (0.43+/-0.62) mm and (0.51+/-0.62) mm
respectively(both P<0.05). (3) Measurements of the aortic annulus diameter by
MSCT including the mean of the long- and short-axis diameters, diameter derived
from cross-sectional area, and diameter derived from the circumference were
larger than the measurement by TTE and TTE (all P<0.05). (4) Implantation was
successful in all patients.Moderate to severe paravalvular leakage was detected
in 3 patients at 7 days post TAVI, and 1 patient developed severe prosthetic
valve restenosis at 6 months post TAVI and received valve-in-valve implantation.
Conclusions: In severe aortic stenosis patients referred for TAVI, the aortic
annular diameter derived from TTE and TEE measurements are smaller than that from
MSCT.In the absence of a gold standard, selection of prosthetic valve type in
TAVI procedure should rely on comprehensive considerations, which is of
importance to get good clinical results for severe aortic stenosis patients
underwent TAVI.
PMID- 28511327
TI - [Determination of iodine content in the left ventricular myocardium of healthy
subjects using dual-source dual-energy CT myocardial first perfusion imaging: a
preliminary study].
AB - Objective: To analyze the normal value of the iodine content in the left
ventricular myocardium of healthy subjects and to observe if there is a segmental
differences on iodine distribution by using the second generation dual-source
dual-energy computed tomography myocardial first perfusion imaging. Methods: In
this retrospective study, 42 healthy subjects, who admitted to our department
between January to June 2016, with normal second generation dual-source dual
energy computed tomography and coronary CT angioghphy (CTA), electrocardiogram
(ECG) results, normal cardiac, hepatic, renal function, normal myocardial enzymes
results were enrolled, data from 38 out of 42 subjects with satisfactory image
quality were analyzed using Siemens Dual Energy-Heart PBV image processing
software.In accordance with the standards of the American Heart Association
myocardial 17 fractionation method, content of iodine was measured at different
segmental left ventricular myocardium and aorta (left coronary artery from the
opening level). The standardized containing iodine value (nIC) was calculated.
Results: The iodine content of left ventricular myocardium in normal subjects was
3.1-7.8 mg/ml.The nIC of myocardium from 1st to 17th segments was 0.28+/-0.06,
0.31+/-0.07, 0.30+/-0.07, 0.30+/-0.04, 0.28+/-0.04, 0.29+/-0.05, 0.29+/-0.01,
0.30+/-0.07, 0.31+/-0.07, 0.27+/-0.06, 0.28+/-0.08, 0.28+/-0.07, 0.29+/-0.08,
0.31+/-0.07, 0.27+/-0.06, 0.29+/-0.06 and 0.21+/-0.07, respectively.The nIC of
the 17th segment was the lowest and was significantly lower than in other
segments (all P<0.05), the nIC was similar among the rest 16 segments (all
P>0.05). Conclusion: The normal iodine content range in left ventricle myocardium
is 3.1-7.8 mg/ml, and the lowest iodine content is detected in the apex and which
is significantly lower than the other left ventricular segments.
PMID- 28511328
TI - [Effects of apolipoprotein E deficiency on sphingosine-1-phosphate distribution
in plasma and lipoproteins of mice].
AB - Objective: To investigate the effects of apolipoprotein E deficiency (Apo E(-/-))
on plasma and lipoprotein distribution of sphingosine-1-phosphate (S1P) in mice.
Methods: Five male or female Apo E(-/-) or wild type (WT) mice were fed with chow
diet and sacrificed at 32-week-age and plasma was collected. The constituents of
lipoprotein(very low density lipoprotein (VLDL), low density lipoprotein (LDL),
high density lipoprotein (HDL)) were separated by ultracentrifuge. The protein
concentration of constituents was detected by BCA protein quantitative kit, and
the S1P concentration in plasma and various lipoprotein constituents was detected
by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Western blot was
used to determine the plasma, liver, and kidney protein expression of
apolipoprotein M(Apo M), which is considered as specific ligand of S1P.The S1P
concentration in plasma and various constituents of lipoprotein in the Apo E(-/-)
mice was compared to respective WT mice. Results: (1)Plasma S1P content was
significantly higher in the Apo E(-/-) groups than that of WT groups (male:
(535.7+/-78.5)nmol/L vs. (263.3+/-22.0)nmol/L; female: (601.1+/-64.0)nmol/L vs.
(279.0+/-33.9)nmol/L; all P<0.01). (2) Compared with WT mice, S1P content in non
HDL(LDL+ VLDL) was significantly higher in Apo E(-/-) mice (male: (504.9+/
52.8)nmol/L vs. (28.7+/-9.0)nmol/L; female: (427.7+/-27.4) vs. (27.8+/
4.7)nmol/L; after standardization of protein concentration, male: (385.0+/
41.2)pmol/mg protein vs. (71.4+/-6.6)pmol/mg protein; female: (330.2+/
22.0)pmol/mg protein vs. (67.2+/-12.1)pmol/mg protein; all P<0.01). (3) The
expression of Apo M in plasma, liver and kidney was significantly higher in Apo
E(-/-) groups than that of WT groups(all P<0.05). Conclusion: The deficiency of
Apo E could lead to upregulated S1P expression in the non-HDL, the underlying
mechanism might be the increased transfer of HDL into the non-HDL by Apo M-S1P.
PMID- 28511331
TI - [Percutaneous ventricular restoration for patients with left ventricular aneurysm
and heart failure after myocardial infarction:4 cases report].
PMID- 28511330
TI - [Successful thrombolysis treatment in one patient with acute cerebral infarction
after atrial fibrilation catheter ablation].
PMID- 28511329
TI - [Therapeutic effect of combined use of FGF1-loaded nano-liposomes and ultrasound
targeted microbubble destruction technique on treating rats with experimental
diabetic cardiomyopathy].
AB - Objective: The therapeutic effect of acid fibroblast growth factor 1(FGF1) on
rats with diabetic cardiomyopathy (DCM) was evaluated by using nano-liposomes
combined with ultrasound-targeted microbubble destruction technique (UTMD).
Methods: The FGF1-loaded nano-liposomes were prepared by water-in-water emulsion
method combined with lyophilization technique.TypeIdiabetes model was induced by
intraperitoneal injection of streptozotocin (STZ, 70 mg/kg) in 60 male SD
rats.Sixteen weeks later, diabetic rats were randomly divided into: placebo group
(saline treatment), FGF1 group, FGF1-loaded nano-liposomes group, and FGF1-loaded
nano-liposomes plus UTMD group (n=15 each). After two weeks of intervention
followed by 2 weeks intervention stop, all rats underwent cardiac
catheterization, and the left ventricular end-systolic pressure (LVESP), left
ventricular end-diastolic pressure (LVEDP) and the maximal increase/decrease rate
of left ventricular pressure (LV+/-dp/dtmax) were measured.Then, the rats were
sacrificed and myocardial tissue were obtained for Masson trichrome staining,
TUNEL apoptotic staining and CD31 immunohistochemistry staining to quantify
myocardial collagen fraction (CVF), cardiac myocyte apoptotic index and
myocardial microvascular density (MVD). Results: (1)Scanning electron microscope
results revealed good morphology and FGF1 encapsulation efficiency (84.3+/-2.8)%
with high stability and dispensability of FGF1 loaded nano-liposomes.(2)The
hemodynamic evaluation showed that LVESP, LV + dp/dt(max) and LV -dp/dt(max) were
all significantly higher, while LVEDP was significantly lower in the FGF1-loaded
nano-liposome+ UTMD group than in DCM group, FGF1 solution group, and FGF1 nano
liposome group(all P<0.05). (3)The Masson trichrome staining demonstrated that
CVF was significantly higher in all DCM groups than in control group and was
significantly lower in the FGF1-loaded nano-liposome+ UTMD group than in DCM
group, FGF1 solution group, and FGF1 nano-liposome group (all P<0.05). (4)The
CD31 immunohistochemical staining results showed that MVD was significantly lower
in all DCM groups than in control group and was significantly higher in the FGF1
loaded nano-liposome+ UTMD group than in DCM group, FGF1 solution group, and FGF1
nano-liposome group (all P<0.05). (5)The TUNEL results showed that apoptotic
index was significantly higher in all DCM groups than in control group and was
significantly lower in the FGF1-loaded nano-liposome + UTMD group than in DCM
group, FGF1 solution group, and FGF1 nano-liposome group (all P<0.05).
Conclusion: FGF1 nano-liposomes combining with UTMD technique can significantly
improve cardiac functions and attenuate myocardial CVF and apoptosis and enhance
myocardial MVD in DCM rats.
PMID- 28511332
TI - [Kounis sysdrome secondary to crucian allergy:a case report].
PMID- 28511333
TI - [Left main artery embolism caused by left atrial myxoma:a case report].
PMID- 28511334
TI - [Meigs syndrome presenting with isolated pericardial effusion: a case report].
PMID- 28511335
TI - [Gene mutations of proprotein convertase subtilisin/kexin type 9 and low density
lipoprotein-cholesterol].
PMID- 28511336
TI - [Research update on the regulation between epicardial adipose tissue and coronary
artery disease].
PMID- 28511337
TI - [Research update on the regulation of monocyte/macrophages by Kruppel-like
factors in atherosclerosis].
PMID- 28511338
TI - [Research update on the hybrid treatment of atrial fibrillation].
PMID- 28511339
TI - Patterns of disease occurrence and management, and public health issues among
Korean populations based on information and experiences obtained by field
epidemiological studies in various situations with episodic stories never been
told.
PMID- 28511340
TI - Review of brucellosis in Nepal.
PMID- 28511341
TI - In vivo and molecular docking studies using whole extract and phytocompounds of
Aegle marmelos fruit protective effects against Isoproterenol-induced Myocardial
infarction in rats.
AB - Myocardial infarction (MI) is a leading major health problem with increased
morbidity and mortality worldwide. The present study investigates isoproterenol
(ISO) induced MI and the beneficial role of Aegle marmelos fruit extract (AMFE)
in rats. Our results indicated the significant augmentation of plasma nitric
oxide (NOx) levels, C-reactive protein (CRP), homocysteine, apolipoprotein B (apo
B), cardiac tissue lipid peroxidation and liver 3-hydroxy-3 methyl glutaryl CoA
(HMG-CoA) reductase activity in ISO treated rats (85mg/kg b.wt) with a
concomitant decrease in plasma apolipoprotein A1 (apo-A), lipase activity,
paraoxonase-1 activity and cardiac tissue taurine levels when compared with
controls. However, pretreatment of ISO administered rats with AMFE (150mg/kg
b.wt/day for 45 days) markedly brought the observed alterations toward near
normal level indicating its protective role against MI. Further, we have extended
our studies to study the interaction of important phytocompounds, marmesin,
marmin, umbelliferone and impertonin, present in AMFE with key enzymes, HMG-CoA
reductase, iNOS, lipoprotein lipase and paraoxonase using AutoDock4. Molecular
docking analysis indicated that HMG-CoA reductase, inducible nitric oxide
synthase (iNOS) and lipoprotein lipase formed a strong enzyme ligand complex with
impertonin. While the marmesin showed strong interaction with paraoxonase enzyme.
In conclusion, our results suggest that AMFE acts as a strong protective agent
against ISO-induced MI, and the bioactive compounds are responsible for this
protective action which is confirmed by molecular docking studies.
PMID- 28511342
TI - Combination of flavonoids from Oroxylum indicum seed extracts and acarbose
improves the inhibition of postprandial blood glucose: In vivo and in vitro
study.
AB - The combined effect of Oroxylum indicum seed extracts (OISE) or major flavonoids
from OISE and acarbose on reducing postprandial blood glucose (PBG) levels was
investigated in vitro and in vivo. In vitro, the IC50 values of OISE and
baicalein against alpha-glucosidase were 43.4+/-0.731MUgmL-1 and 25.9+/
0.412MUgmL-1 respectively. A combination of acarbose with OISE or baicalein
synergistically inhibited rat intestinal alpha-glucosidase. The combination index
(CI) values for acarbose with OISE ranged from 0.33 to 0.75, suggesting a
synergistic but not additive effect. OISE was determined to be a non-competitive
inhibitor of maltose-hydrolyzing activity. In vivo, OISE were administered to
normoglycemic and diabetic mice, either alone or in combination with acarbose. At
doses between 50 and 200mgkg-1, OISE enhanced the efficacy of acarbose by up to 5
fold. These results demonstrated that OISE enhances the efficacy of acarbose in
vivo, and that the combination of OISE and acarbose displayed a synergistic
effect in vitro. Therefore, OISE can be used to design dietary supplements to
treat diabetes.
PMID- 28511343
TI - Restoration of miR-143 expression could inhibit migration and growth of MDA-MB
468 cells through down-regulating the expression of invasion-related factors.
AB - INTRODUCTION: Breast adenocarcinoma is the second common cancer in women the
incidence of which is increasing in many countries, especially in developing
companies. In this study, miRNA143 has been replaced by vector based microRNA-143
in breast adenocarcinoma cells (MDA-MB-468) and its anti-cancer effects on breast
adenocarcinoma cells have been evaluated. METHODS: The pCMV-MIR-143 vector was
transfected into MDA-MB-468 cells via JetPEI transfection reagent. The
transfected cells were selected by IC50 concentration of Geneticin antibiotic
(G418) after a 2-week treatment. To evaluate the effect of miR-143 on the
inhibition of migration, scratch wound healing assay was performed. Then, the
expression level of miR-143, Kras, Vimentin, CXCR4, MMP9 and E-Cadherin were
measured by the qRT-PCR method. RESULTS: Results of MTT and wound healing assays
showed that miR-143 inhibited cell growth and cell migration in miR-143 induced
cell line compared with control group. The result of gene expression showed that
miR-143 reduced Kras, Vimentin, CXCR4 and MMP9 expression, and increased E
Cadherin expression in miR-143 replaced cells compared to control cells.
CONCLUSION: The results showed that miRNA-143 plays an important role in cell
growth and migration during breast cancer development and metastasis and it can
be a candidate as a therapeutic molecule in microRNA replacement therapy of
breast adenocarcinoma.
PMID- 28511344
TI - Anti-inflammatory effects of trans-anethole in a mouse model of chronic
obstructive pulmonary disease.
AB - Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung
disease that is generally characterized by progressive and irreversible airflow
obstruction and alveolar destruction. Long-term treatment with current
medications has been associated with various adverse effects, indicating a need
for alternative approaches for the prevention and treatment of COPD. This study
investigated the mechanism underlying the effects of trans-anethole in a mouse
model of COPD induced by porcine pancreatic elastase (PPE) and lipopolysaccharide
(LPS). BALB/c mice were orally administered trans-anethole (62.5, 125, 250, or
500mg/kg) 2h before intranasal challenge with 1.2 units of PPE and 7MUg of LPS.
Lactate dehydrogenase (LDH) activity, cell counts, lung histology, cytokine
production, and blood pressure were analyzed. Trans-anethole reduced LDH activity
and inflammatory cell counts, including macrophage, neutrophil, and lymphocyte
counts. trans-anethole 125mg/kg restored the histopathological changes induced in
mouse lungs by PPE and LPS. trans-anethole reduced the serum concentrations of
pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis
factor-alpha (TNF-alpha), as well as significantly reducing blood pressure during
chronic inflammation. Trans-anethole ameliorated chronic lung inflammation in a
mouse model of COPD by reducing the serum concentrations of pro-inflammatory
cytokines such as TNF-alpha and IL-6, and by reducing blood pressure. The present
results indicate that trans-anethole may be a potential therapeutic agent for
prophylaxis and treatment in patients with chronic lung inflammation.
PMID- 28511345
TI - ROS homeostasis, a key determinant in liver ischemic-preconditioning.
AB - Reactive Oxygen Species (ROS) are key mediators of ischemia-reperfusion injury
but also required for the induction of the stress response that limits tissue
injury and underlies the protection provided by ischemic-preconditioning
protocols. Liver steatosis is an important risk factor for liver transplant
failure. Liver steatosis is associated with mitochondrial dysfunction and
excessive mitochondrial ROS production. Studies aiming at decreasing the
sensibility of the steatotic liver to ischemia-reperfusion injury using pre
conditioning protocols, have shown that the steatotic liver has a reduced
capacity to respond to these protocols. Recent studies indicate that these
effects are related to a reduced capacity of the steatotic liver to respond to
elevated ROS levels following reperfusion by inducing a compensatory response.
This failure to respond to ROS is associated with reduced levels of antioxidants,
mitochondrial damage, hepatocyte cell death, activation of the immune system and
induction of pro-fibrotic mediators.
PMID- 28511349
TI - Brown and black carbon in Beijing aerosol: Implications for the effects of brown
coating on light absorption by black carbon.
AB - Brown carbon (BrC) is increasingly included in climate models as an emerging
category of particulate organic compounds that can absorb solar radiation
efficiently at specific wavelengths. Water-soluble organic carbon (WSOC) has been
commonly used as a surrogate for BrC; however, it only represents a limited
fraction of total organic carbon (OC) mass, which could be as low as about 20% in
urban atmosphere. Using methanol as the extraction solvent, up to approximately
90% of the OC in Beijing aerosol was isolated and measured for absorption spectra
over the ultraviolet-to-visible wavelength range. Compared to methanol-soluble OC
(MSOC), WSOC underestimated BrC absorption by about 50% at 365nm. The mass
absorption efficiencies measured for BrC in Beijing aerosol were converted to the
imaginary refractive indices of BrC and subsequently used to compute BrC coating
induced enhancement of light absorption (Eabs) by black carbon. Eabs attributed
to lensing was reduced in the case of BrC coating relative to that caused by
purely-scattering coating. However, this reduction was overwhelmed by the effect
of BrC shell absorption, indicating that the overall effect of BrC coating was an
increase in Eabs. Methanol extraction significantly reduced charring of OC during
thermal-optical analysis, leading to a large increase in the measured elemental
carbon (EC) mass and an apparent improvement in the consistency of EC
measurements by different thermal-optical methods.
PMID- 28511348
TI - Integrated flood hazard assessment based on spatial ordered weighted averaging
method considering spatial heterogeneity of risk preference.
AB - Flood is the most common natural hazard in the world and has caused serious loss
of life and property. Assessment of flood prone areas is of great importance for
watershed management and reduction of potential loss of life and property. In
this study, a framework of multi-criteria analysis (MCA) incorporating geographic
information system (GIS), fuzzy analytic hierarchy process (AHP) and spatial
ordered weighted averaging (OWA) method was developed for flood hazard
assessment. The factors associated with geographical, hydrological and flood
resistant characteristics of the basin were selected as evaluation criteria. The
relative importance of the criteria was estimated through fuzzy AHP method. The
OWA method was utilized to analyze the effects of different risk attitudes of the
decision maker on the assessment result. The spatial ordered weighted averaging
method with spatially variable risk preference was implemented in the GIS
environment to integrate the criteria. The advantage of the proposed method is
that it has considered spatial heterogeneity in assigning risk preference in the
decision-making process. The presented methodology has been applied to the area
including Hanyang, Caidian and Hannan of Wuhan, China, where flood events occur
frequently. The outcome of flood hazard distribution presents a tendency of high
risk towards populated and developed areas, especially the northeast part of
Hanyang city, which has suffered frequent floods in history. The result indicates
where the enhancement projects should be carried out first under the condition of
limited resources. Finally, sensitivity of the criteria weights was analyzed to
measure the stability of results with respect to the variation of the criteria
weights. The flood hazard assessment method presented in this paper is adaptable
for hazard assessment of a similar basin, which is of great significance to
establish counterplan to mitigate life and property losses.
PMID- 28511346
TI - Potential therapeutic action of nitrite in sickle cell disease.
AB - Sickle cell disease is caused by a mutant form of hemoglobin that polymerizes
under hypoxic conditions, increasing rigidity, fragility, calcium influx-mediated
dehydration, and adhesivity of red blood cells. Increased red cell fragility
results in hemolysis, which reduces nitric oxide (NO) bioavailability, and
induces platelet activation and inflammation leading to adhesion of circulating
blood cells. Nitric Oxide inhibits adhesion and platelet activation. Nitrite has
emerged as an attractive therapeutic agent that targets delivery of NO activity
to areas of hypoxia through bioactivation by deoxygenated red blood cell
hemoglobin. In this study, we demonstrate anti-platelet activity of nitrite at
doses achievable through dietary interventions with comparison to similar doses
with other NO donating agents. Unlike other NO donating agents, nitrite activity
is shown to be potentiated in the presence of red blood cells in hypoxic
conditions. We also show that nitrite reduces calcium associated loss of
phospholipid asymmetry that is associated with increased red cell adhesion, and
that red cell deformability is also improved. We show that nitrite inhibits red
cell adhesion in a microfluidic flow-channel assay after endothelial cell
activation. In further investigations, we show that leukocyte and platelet
adhesion is blunted in nitrite-fed wild type mice compared to control after
either lipopolysaccharide- or hemolysis-induced inflammation. Moreover, we
demonstrate that nitrite treatment results in a reduction in adhesion of
circulating blood cells and reduced red blood cell hemolysis in humanized
transgenic sickle cell mice subjected to local hypoxia. These data suggest that
nitrite is an effective anti-platelet and anti-adhesion agent that is activated
by red blood cells, with enhanced potency under physiological hypoxia and in
venous blood that may be useful therapeutically.
PMID- 28511350
TI - On the applicability of a hybrid bioreactor operated with polymeric tubing for
the biological treatment of saline wastewater.
AB - Effective biological treatment of high salt content wastewater requires
consideration of both salt and organic toxicity. This study treated a synthetic
saline wastewater containing NaCl (100gL-1) and 2,4-dimethylphenol (1.2gL-1) with
a hybrid system consisting of a biological reactor containing spiral-coiled
polymeric tubing through which the mixed feed was pumped. The tubing wall was
permeable to the organic contaminant, but not to the salt, which allowed transfer
of the organic into the cell-containing bioreactor contents for degradation,
while not exposing the cells to high salt concentrations. Different grades of
DuPont Hytrel polymer were examined on the basis of organic affinity predictions
and experimental partition and mass transfer tests. Hytrel G3548 tubing showed
the highest permeability for 2,4-dimethylphenol while exerting an effective salt
barrier, and was used to verify the feasibility of the proposed system. Very high
organic removal (99% after just 5h of treatment) and effective biodegradation of
the organic fraction of the wastewater (>90% at the end of the test) were
observed. Complete salt separation from the microbial culture was also achieved.
PMID- 28511347
TI - Mitochondrial complex I deactivation is related to superoxide production in acute
hypoxia.
AB - Mitochondria use oxygen as the final acceptor of the respiratory chain, but its
incomplete reduction can also produce reactive oxygen species (ROS), especially
superoxide. Acute hypoxia produces a superoxide burst in different cell types,
but the triggering mechanism is still unknown. Herein, we show that complex I is
involved in this superoxide burst under acute hypoxia in endothelial cells. We
have also studied the possible mechanisms by which complex I could be involved in
this burst, discarding reverse electron transport in complex I and the
implication of PTEN-induced putative kinase 1 (PINK1). We show that complex I
transition from the active to 'deactive' form is enhanced by acute hypoxia in
endothelial cells and brain tissue, and we suggest that it can trigger ROS
production through its Na+/H+ antiporter activity. These results highlight the
role of complex I as a key actor in redox signalling in acute hypoxia.
PMID- 28511352
TI - Emission inventory and environmental distribution of decabromodiphenyl ether in
China.
AB - Decabromodiphenyl ether (decaBDE) is a highly brominated flame retardant that
recent studies have identified as a potential persistent organic pollutant. Large
amounts of decaBDE have been consumed and released in the environment in China,
while no emission inventory has been available until now. In this study, a
substance flow analysis was applied to establish the emission inventory of
decaBDE in China from 1982 (the first year of decaBDE production in China) until
2013 based on activity data, transfer coefficients, and emission factors. The
results show that the stock of decaBDE continually increased, reaching a peak of
290,000tons in 2007. The annual processing capacity of decaBDE also increased,
and the processing capacity in 2013 was 49,000tons. Historical accumulative
emissions were estimated to be 313.3tons from 1982 to 2013, and the annual
emissions peaked in 2003 at 27.5tons. On average, decaBDE processing was the
major source (58.4%) of total emissions, followed by treatment, production, and
usage processes. From 1982 to 2013, decaBDE was released mainly into water
sources, accounting for 50.7% of the accumulative emissions. At the provincial
level, Guangdong, Shandong, and Zhejiang provinces were the largest producers in
China. Simulations produced by the level III fugacity model showed that the
projected concentration was very consistent with the measured value. The stock of
decaBDE in the soil and sediment phases accounted for 99.8% of the total stock,
and the transfer among the four environmental phases occurred mainly at the
atmosphere-soil interface.
PMID- 28511351
TI - Effects of various fertilization regimes on abundance and activity of anaerobic
ammonium oxidation bacteria in rice-wheat cropping systems in China.
AB - Anaerobic ammonium oxidation (anammox) is an important process in many marine and
paddy ecosystems. However, few studies have reported on the contribution to the
nitrogen cycle of anammox and its dynamics in rice-wheat cropping systems with
different fertilization regimes. Here, isotope tracing and molecular techniques
were used to determine the potential rates of anammox and their association with
bacterial abundance, diversity, and activity. Rice-wheat cropping systems at two
sites in Jiangsu Province, China were selected and the treatments at each site
were: 1) no fertilization (CK), 2) 100% chemical fertilization (CF), 3) pig
manure compost plus 50% chemical fertilization (PMCF), and 4) straw plus 100%
chemical fertilization (SRCF). The results revealed that anammox bacteria with
high abundance were detected in both the wheat and rice seasons. The abundance of
anammox in PMCF treatment was higher than that in SRCF treatment in both Changshu
and Jintan. Moreover, the abundance of anammox bacteria in CF treatment was
significantly higher than that in CK in Changshu. Analysis of anammox hydrazine
synthase beta subunit (hzs-beta) gene sequences showed that in the rice season,
the anammox bacteria Ca. Brocadia, Ca. Scalindua, and Ca. Jettenia were present.
In contrast, all of the anammox hydrazine oxidase (hzo) genes were affiliated
with Ca. Brocadia, suggesting that hzs genes are more representative of anammox
biological diversity compared to hzo. Sequences from the PMCF treatment where
affiliated with both Ca. Jettenia and Ca. Brocadia, and showed the highest
diversity. Anammox activity was detected in both the wheat and rice seasons, but
there were significant differences between seasons. The anammox rates were in the
range 0.34 to 1.04nmol dinitrogen gas?g-1 dry soil?h-1, and 3.15 to 9.62% of
dinitrogen gas emissions were attributed to anammox. However, no significant
difference among the fertilizer treatments for anammox activity was found in the
study.
PMID- 28511353
TI - Assessment of water retention function as tool to improve integrated watershed
management (case study of Poprad river basin, Slovakia).
AB - The presented study concentrates on assessing the ecosystem function of water
retention. The water retention function is defined as the ability of the
landscape to retain water, slow runoff and encourage water infiltration. The
water retention function was expressed by calculating the hydric significance
(HS) indicator. This method is based on scoring the individual input parameters
according to their overall impact on watershed hydrology. The study was conducted
on a sample area of Poprad River basin. The final results presented a spatial
distribution of hydric function within the watershed classified according to its
significance into four classes (from limited to excellent significance). A
breakdown of the results on the level of elementary watersheds was used in order
to examine those with low hydric function. The results showed a significant
influence of land-use on retention function; however, this impact could be
limited by extreme precipitation or high soil water saturation. The methodology
of hydric significance represents an innovative approach towards assessment of
ecosystem function of water retention on regional level.
PMID- 28511354
TI - Occurrence, distribution and sources of bisphenol analogues in a shallow Chinese
freshwater lake (Taihu Lake): Implications for ecological and human health risk.
AB - Since the production and use of BPA were regulated in China around 2008, several
bisphenol analogues were widely used to substitute BPA in the manufacture of
polycarbonates, epoxy resins, and plastics. However, there is limited
understanding of the spatial distribution, potential sources and risk assessment
for those bisphenol analogues. In this study, seven bisphenol analogues were
investigated in water and sediment samples from Taihu Lake, China. Compared to
the same lake in 2013 (range: 5.4-87ng/L for waters and 0.37-8.3ng/g dw for
sediments), the samples from Taihu Lake contained comparatively higher BPs
(2.0*102-9.5*102ng/L and 23-4.3*102ng/gdw) in 2016, indicating that the BPs
levels in Taihu Lake have aggravated recently. In waters, BPAF has become the
predominant congener in Taihu Lake, suggesting that BPAF was the most widely used
substitute of BPA, recently. In sediments, BPA was the most abundant compound.
Moderate or strong correlations between some individual BPs indicated that those
BPs may have the common sources and/or similar environmental behavior. The
strongly positive correlation between ?BPs and TOC content indicated that TOC
content was one of the major factors controlled the distribution of ?BPs in the
sediment. The risk assessment at the sampling sites showed no high eco-toxicity
or estrogenic risk in Taihu Lake.
PMID- 28511355
TI - Identification of polar transformation products and high molecular weight
polycyclic aromatic hydrocarbons (PAHs) in contaminated soil following
bioremediation.
AB - Bioremediation is a technique commonly used to reduce the toxicity associated
with polycyclic aromatic hydrocarbons (PAHs) in contaminated soils. However, the
efficacy of bioremedial applications is evaluated based on the removal of a
subset of parent (or unsubstituted) PAHs and does not incorporate toxic polar
transformation products or the more mutagenic high molecular weight PAHs
(MW>=302amu or MW302-PAHs). Previously, an effects-directed analysis approach was
used to assess the effect of bioremediation on the toxicity of a coal tar
contaminated soil. Increased genotoxicity and developmental toxicity was measured
postbioremedation in the more polar soil extract fractions, as compared to the
less polar fractions where the targeted PAHs eluted, and could not be attributed
to the 88 target PAHs analyzed for (including selected oxygen-containing PAHs).
In this study, comprehensive two-dimensional gas chromatography time-of-flight
and liquid chromatography quadrupole time-of-flight mass spectrometry were used
to characterize transformation products in the soil extract fractions identified
as toxic, previously. Additionally, the degradation of 12MW302-PAHs, picene
(MW=278) and coronene (MW=300) were evaluated following bioremediation. Non
targeted analysis resulted in the tentative identification of 10 peaks with
increased intensity postbioremediation (based on mass spectral library matching
and fragmentation patterns from >5000 candidate peaks in the soil extracts).
Several of these compounds contained oxygen, suggesting they would be relatively
polar. MW302-PAHs were not significantly degraded during bioremediation,
suggesting that the carcinogenic potential associated with these PAHs might
remain unchanged. The results of this study suggest that polar transformation
products, and MW302-PAHs, should be considered for realistic risk assessment of
bioremediated soils.
PMID- 28511356
TI - Effects of sewage effluents and seasonal changes on the metabolism of three
Atlantic rivers.
AB - Sewage inputs on fluvial ecosystems affect benthic communities and alter trophic
networks resulting in changes on river functioning. Functional indicators (e.g.
river metabolism) have been proposed as a valuable tool to evaluate ecosystem
impairment. In the present study we monitored river metabolism in spring (few
days after a major flood) and in summer (after 35days of low flow conditions)
using both single-station and two-stations methods over a 24h period up and
downstream of wastewater treatment plant (WWTP) effluents on three Atlantic river
reaches located in northern Spain (Europe). Concurrently with river metabolism,
we characterized environmental characteristics (flow, velocity, depth, pH, water
temperature, nutrients, etc.), benthic macroinvertebrate communities and biofilm
(algae and epilithic biomass). Ecosystem Respiration (ER24) was similar at the
different periods and locations, but Gross Primary Productivity (GPP) tended to
decrease in impacted reaches (downstream WWTPs) and in summer (except in the Saja
River). However, the balance of the metabolic processes showed a trend towards
autotrophy in the largest river, while WWTP effluents increased its autotrophy.
Chlorophyll a concentration was >4 times larger in spring than in summer in all
river reaches, while epilithic biomass followed a similar but less obvious
pattern. Increase of invertebrate scraper densities (mainly, Potamopyrgus
antipodarum) seems to be a plausible explanation for biofilm biomass temporal
patterns in all sites (higher in spring than in summer), altering GPP and ER24
patterns. Thus, metabolism rates show different responses to WWTP effluents
depending on season and on the relationships among functional and structural
components, with special focus on the composition and structure of
macroinvertebrate communities. Increasing our understanding of cause-effect
relationships on the impairment of aquatic ecosystems needs to account for both
structural and functional components and their interactions.
PMID- 28511358
TI - The degree of phosphorus saturation of agricultural soils in Germany: Current and
future risk of diffuse P loss and implications for soil P management in Europe.
AB - Decades of intensive agricultural production with excessive application of P
fertilizer have resulted in the accumulation of P in soils, threatening water
bodies in most industrialized countries with eutrophication. In our study, we
elucidated the risk of P loss of German agricultural soils by transforming
provided monitoring data of plant-available P determined by the calcium-acetate
lactate (PCAL) and double-lactate method (PDL) into the degree of phosphorus
saturation (DPS). As water-soluble phosphorus (WSP) is correlated to DPS, we
derived a pedotransfer function (PTF) between PCAL and WSP for different soil
types. Considering all soils together resulted in WSP=0.1918*PCAL (R2=0.80,
n=54). Subsequently, risk parameters DPS and EPC0 were calculated from PCAL and
PDL monitoring data (n>337,000) by using the determined PTF and soil type
independent correlations with WSP, as published in an earlier study. Calculated
DPS values from monitoring data indicated high risks of dissolved P loss for >76%
of German arable soils. Recent suggestions by the Association of German
Agricultural Analytical and Research Institutes (VDLUFA) to reduce recommended
PCAL levels are crucial for the reduction of P loss risks in the future. The
accuracy of predicted DPS and EPC0 values by CAL and other methods used in Europe
to estimate plant-available P is limited by the soil type-dependency of these
methods. Consequently, we recommend considering WSP as an agri-environmental soil
P test across Europe. Our results indicate that a WSP level in soils can be
defined that constitutes a reasonable compromise between the securing of
agronomic production and the fulfillment of environmental goals.
PMID- 28511357
TI - Establishing and testing a catchment water footprint framework to inform
sustainable irrigation water use for an aquifer under stress.
AB - Future water scarcities in the face of an increasing population, climate change
and the unsustainable use of aquifers will present major challenges to global
food production. The ability of water footprints (WFs) to inform water resource
management at catchment-scale was investigated on the Steenkoppies Aquifer, South
Africa. Yields based on cropping areas were multiplied with season-specific WFs
for each crop to determine blue and green water consumption by agriculture.
Precipitation and evapotranspiration of natural vegetation and other uses of blue
water were included with the agricultural WFs to compare water availability and
consumption in a catchment sustainability assessment. This information was used
to derive a water balance and develop a catchment WF framework that gave
important insights into the hydrology of the aquifer through a simplified method.
This method, which requires the monitoring of only a few key variables, including
rainfall, agricultural production, WFs of natural vegetation and other blue water
flows, can be applied to inform the sustainability of catchment scale water use
(as opposed to more complex hydrological studies). Results indicate that current
irrigation on the Steenkoppies Aquifer is unsustainable. This is confirmed by
declining groundwater levels, and suggests that there should be no further
expansion of irrigated agriculture on the Steenkoppies Aquifer. Discrepancies
between in- and outflows of water in the catchment indicated that further
development of the WF approach is required to improve understanding of the
geohydrology of the aquifer and to set and meet sustainability targets for the
aquifer. It is envisaged that this 'working' framework can be applied to other
water-stressed aquifers around the world.
PMID- 28511359
TI - Occurrence of chemical contaminants in peri-urban agricultural irrigation waters
and assessment of their phytotoxicity and crop productivity.
AB - Water scarcity and water pollution have increased the pressure on water resources
worldwide. This pressure is particularly important in highly populated areas
where water demand exceeds the available natural resources. In this regard, water
reuse has emerged as an excellent water source alternative for peri-urban
agriculture. Nevertheless, it must cope with the occurrence of chemical
contaminants, ranging from trace elements (TEs) to organic microcontaminants. In
this study, chemical contaminants (i.e., 15 TEs, 34 contaminants of emerging
concern (CECs)), bulk parameters, and nutrients from irrigation waters and crop
productivity (Lycopersicon esculentum Mill. cv. Bodar and Lactuca sativa L. cv.
Batavia) were seasonally surveyed in 4 farm plots in the peri-urban area of the
city of Barcelona. A pristine site, where rain-groundwater is used for
irrigation, was selected for background concentrations. The average concentration
levels of TEs and CECs in the irrigation water impacted by treated wastewater
(TWW) were 3 (35+/-75MUgL-1) and 13 (553+/-1050ngL-1) times higher than at the
pristine site respectively. Principal component analysis was used to classify the
irrigation waters by chemical composition. To assess the impact of the occurrence
of these contaminants on agriculture, a seed germination assay (Lactuca sativa L)
and real field-scale study of crop productivity (i.e., lettuce and tomato) were
used. Although irrigation waters from the peri-urban area exhibited a higher
frequency of detection and concentration of the assessed chemical contaminants
than those of the pristine site (P1), no significant differences were found in
seed phytotoxicity or crop productivity. In fact, the crops impacted by TWW
showed higher productivity than the other farm plots studied, which was
associated with the higher nutrient availability for plants.
PMID- 28511360
TI - Refined 2013-based vehicle emission inventory and its spatial and temporal
characteristics in Zhengzhou, China.
AB - Vehicle emission is becoming one of the most important pollution sources because
of the increase in vehicle population and activity in China. A more reasonable
and complete vehicle emission inventory in Zhengzhou for the year 2013 was
developed in this study. This inventory is suitable for local emission factors
and vehicle kilometers of travel. Estimates show that the total carbon monoxide
(CO), hydrocarbon (HC), nitrogen oxide (NOX), particulate matter (PM2.5 and PM10)
and sulfur dioxide (SO2) emissions were 291Gg, 35Gg, 106Gg, 6Gg, 7Gg, and 3Gg,
respectively. Approximately 55% of CO and HC emissions were from light duty
gasoline vehicles and normal gasoline motorcycles, whereas approximately 60% of
NOX, PM2.5, PM10 and SO2 were from heavy duty diesel vehicles, heavy duty diesel
trucks, and medium duty diesel trucks. The spatial distribution of emissions was
allocated in grid cells based on a road network and traffic flows with a
resolution of 1km*1km at different road types and locations, which shows that the
six aforementioned air pollutants have similar characteristics in administrative
districts. Emissions are mainly concentrated on the central grid cells of each
part and in good agreement with line sources. The spatial characteristics were
compared at a resolution of 3km*3km and in a population-based approach. The
network approach yields better level estimates in this study. Meanwhile, the
preliminary temporal profiles were also established for on-road mobile source.
PMID- 28511361
TI - Predicting phosphorus availability from chemically diverse conventional and
recycling fertilizers.
AB - Fertilizers produced from heterogeneous, phosphorus-rich biowastes are becoming
increasingly relevant. Treatment and processing (combustion, pyrolysis, anaerobic
digestion, etc.) increase the diversity of their physico-chemical composition
even further. We investigated several approaches to characterize P availability
from a set of 13 contrasting fertilizers. We tested them directly using standard
fertilizer extractions, as well as a continuous, sink-based P extraction (iron
bag) method. We also performed Olsen, CAL and diffusive gradients in thin films
(DGT) tests on fertilized soil. Standard extractions correlated only weakly,
whereas the iron bag method correlated highly (0.732 MUg/ml) was
seen in 12 (8.3%) isolates (eight K.pneumoniae and four E. coli). Eight other
isolates were found to have MIC of 2 MUg/ml and thus the overall prevalence of
isolates with decreased susceptibility was 20 (13.9%). CONCLUSION: A high
prevalence of carbapenem resistance coupled with high tigecycline MICs in
clinical isolates of E.coli and K. pneumoniae highlights the judicious use of a
combination of antimicrobials. Routine in vitro sensitivity testing to evaluate
the clinical utility of tigecycline against such resistant Enterobacteriaceae is
warranted.
PMID- 28511384
TI - Community Acquired Burkholderia cepacia Bacteraemia Presenting as MODS in an
Immunocompetent Individual: An Unusual Case.
AB - Burkholderia cepacia has been recognized as a group of highly virulent organisms
known as Burkholderia cepacia complex (Bcc). Bcc are ubiquitous in nature and
most commonly found in moist environment, on plant roots and soil. Because of its
high intrinsic antibiotic resistance, Bcc is a major cause of morbidity and
mortality in hospitalized patients. It is reported most commonly in
immunocompromised patients especially in patients with cystic fibrosis. Here, we
report a rare case report of bacteraemia by Burkholderia cepacia in an
immunocompetent male, who presented with fever and Multiple Organ Dysfunction
Syndrome (MODS). Burkholderia cepacia was isolated from his blood culture, which
he acquired from his work place. He was treated successfully and discharged after
negative blood culture.
PMID- 28511382
TI - Rapid Identification of Vancomycin Resistant Enterococcus Faecalis Clinical
Isolates using a Sugar Fermentation Method.
AB - INTRODUCTION: Vancomycin Resistant Enterococci (VRE) can be found all over the
world. Thus, rapid detection of the isolates could be of high importance in the
treatment or prevention of the associated disease. AIM: To measure the turanose
fermentation in Enterococcus faecalis clinical isolates for rapid differentiation
of VRE and Vancomycin-Susceptible E. faecalis (VSE) isolates. MATERIALS AND
METHODS: Forty E. faecalis samples were isolated from 200 clinical samples in
Tehran Medical Center, Iran, from October 2012 to December 2012. These isolates
were detected according to the standard microbial and biochemical tests.
Detection of VRE isolates was originally performed by disk diffusion using 1 MUg
vancomycin disk, followed by Polymerase Chain Reaction (PCR) amplification of the
vanA gene. Finally, the turanose consumption in 1%, 0.7% and 0.5% dilutions was
detected by a phenotypic method. RESULTS: Among the 40 E. faecalis isolates, 20
vancomycin-susceptible and 20 vancomycin-resistant E. faecalis were isolated
according to the disk diffusion and PCR of the vanA gene. There was a
considerable difference between VRE and VSE isolates in 0.7% dilution of
turanose. However, there was no significant difference between VRE and VSE in 1%
and 0.5% dilutions of turanose. CONCLUSION: Since detection of VRE isolates is of
high importance, especially in nosocomial infections, phenotypic methods may be
highly useful for this purpose. In conclusion, our data indicate that VRE
isolated from clinical samples could be distinguished from VSE isolates by
turanose fermentation at dilution 0.7%.
PMID- 28511385
TI - Intra-operative Diagnosis of Breast Lesions by Imprint Cytology and Frozen
Section with Histopathological Correlation.
AB - INTRODUCTION: The most common malignant tumour among women is breast carcinoma.
Early lesions of the breast including carcinoma are potentially curable if
treated properly in the era of breast conservative therapy. For this purpose
different diagnostic strategies are in practice. Intra operative Imprint Cytology
(IC) and Frozen Section (FS) have a role in spite of the intense recognition of
aspiration cytology in the following settings: inconclusive cytological/core
biopsy findings; for evaluation of lumpectomy margins and intra operative nodal
status. Both IC and FS are dependable intra operative diagnostic consultation
modalities and provide accurate results in minutes thereby making appropriate
therapeutic decision. AIM: To study the IC and FS features of breast lesions with
correlation of final Histopathologic (HP) diagnosis and to determine its
diagnostic accuracy. MATERIALS AND METHODS: This was a descriptive cross
sectional study conducted in the Department of Pathology, JSS Medical College,
JSS University, Mysuru over a period of two years (October 2011-September 2013).
A total of 62 cases of surgically resected breast specimens were evaluated for
features of IC, FS and correlation with HP diagnosis. After describing gross
features, representative tissue fragment was taken, three imprint smears were
made and same tissue fragment was subjected to FS and later for routine HP
processing. Slides prepared by IC, FS were interpreted and later correlated with
HP diagnosis. Statistical analysis was done with SPSS for windows (version 16.0)
by applying appropriate tests. RESULTS: Out of 62 cases, 33(53.23%) were
malignant and 29(46.77%) were benign. Sensitivity, specificity and accuracy of IC
were 100%, 96.43% and 98.36% and for FS were 100%, 96.55% and 98.39%
respectively. p-value for both were <0.001 indicating significant correlation
with HP study. CONCLUSION: IC is a simple, accurate, rapid and cost effective
diagnostic tool intra operatively where services for FS are not available. It
preserves crisp cellular and nuclear detail. FS tissue architecture strongly
approximates permanent HP sections but is frequently hampered by freezing
artifact. But FS is able to differentiate carcinoma in situ and infiltrative
lesions from benign breast lesions. Thus, IC and FS together offer a more
reliable diagnosis; hence, it is always useful to prepare both the slides intra
operatively. HP study still remains the gold standard in final diagnosis of any
breast lesion. In surgical pathology, the correlation of intra operative IC and
FS diagnosis with the final HP diagnosis form an essential part of quality
assurance activity.
PMID- 28511386
TI - Assessment of Disease Severity and Role of Cytomegalo Virus Infection in Patients
with Ulcerative Colitis.
AB - INTRODUCTION: Course of Ulcerative Colitis is characterized by intermittent
flares interposed between variable periods of remission. Identification of
exacerbating factors and appropriate assessment of disease activity are crucial
in deciding the choice of treatment. AIM: To evaluate various clinical,
endoscopic and histological parameters in assessing disease activity and to find
out various risk factors involved in the exacerbation of ulcerative colitis
especially the role of Cytomegalo Virus (CMV) infection. MATERIALS AND METHODS:
It was a prospective study of patients diagnosed as ulcerative colitis presenting
with acute exacerbation of symptoms (cases) and those who were in remission
(controls). A detailed evaluation of the disease history including personal
history, treatment compliance and clinical disease severity were noted.
Investigations including blood routine, endoscopic examination with biopsy,
histopathological examination and immunohistochemistry for CMV were done on the
biopsy sample. RESULTS: A total of 58 patients with ulcerative colitis were
studied which included 37 cases and 21 controls. Out of the various clinical and
demographic parameters, Good treatment compliance (p =0.0003) and Perceived
Stress Scale (PSS) score (p=0.0001) showed significant difference between cases
and controls. Basic laboratory parameters {Haemoglobin level, Total Leucocyte
Count (TLC) and Erythrocyte Sedimentation Rate (ESR)}, clinical disease severity
predictors (Truelove and Witt's criteria, Mayo score and endoscopic disease
severity grade) and Geboes histological scoring showed significant difference
between cases and controls. The prevalence of CMV colitis in our study was only
5.4% (two cases). CONCLUSION: Clinical and endoscopic disease severity indicators
can be used as predictors of histological activity in ulcerative colitis. Poor
treatment compliance and stress are important risk factors for acute exacerbation
of ulcerative colitis. Clinicians should be aware of the possibility of
concurrent CMV infection while treating patients with acute exacerbation of
ulcerative colitis not responding to the conventional management. Reduced
prevalence of CMV colitis in cases of acute exacerbation of ulcerative colitis in
our study may be due to the small sample size, reduced number of steroid
dependent cases or reduced severity of our cases.
PMID- 28511387
TI - Erythrocyte Alloimmunization and Autoimmunization among Blood Donors and
Recipients visiting a Tertiary Care Hospital.
AB - INTRODUCTION: The ultimate aim of pretransfusion testing is the acceptable
survival of donor red cells in recipient's body and antibody detection plays a
critical role in achieving the same. The cornerstone of antibody detection method
is detecting an unexpected antibody as against the expected antibodies of ABO
blood group system. Autoantibodies can also interfere with the detection of
clinically significant alloantibodies. AIM: To study the frequency of
alloantibodies and autoantibodies in the healthy blood donors and patient
population visiting our hospital. MATERIALS AND METHODS: The Column Agglutination
Technology (CAT) was used for ABO RhD blood grouping, Direct Antiglobulin Test
(DAT), Autocontrol (AC), Indirect Antiglobulin Test (IAT) and red cell antibody
screening and the unexpected reactions in any of these tests were recorded for
further evaluation. Ethylene Diamine Tetra Acetic Acid (EDTA) blood samples were
used for all these tests for both blood donors and admitted patients. The CAT was
exercised for the blood grouping (using ABD-Reverse Diluent cassettes) and
antibody screening (using 0.8% Surgiscreen, Ortho Clinical Diagnostics Limited,
USA and Low Ionic Strength Saline Ortho BLISS with AHG cassettes) on the
automated immunohaematology platform ORTHO AutoVue(r) Innova system (Ortho
Clinical Diagnostics Limited, USA). RESULTS: Among all blood donors (n=6350),
seven (0.11%) donors had showed unexpected reaction. Of these, four had positive
antibody screen (three having naturally occuring antibodies 2=anti-M, 1=anti-Lea
and 1=inconclusive) and the other three had positive DAT. Of all the patient
samples (n=6136) screened for irregular red cell antibodies, four (0.06%)
patients were found to have unexpected reaction revealing one (0.02%) with anti-M
antibody and the other three (0.05%) had autoantibodies in their serum.
CONCLUSION: The combined prevalence for both blood donor and recipient population
(n=12,486) was found to be 0.11% at our center. The alloimmunisation among
patient population was found to be lower than many other studies worldwide as our
hospital does not cater to multitransfused or transfusion dependant patients with
haematological disorders and majorly elective surgery patients with no history of
previous blood transfusions visit our hospital.
PMID- 28511388
TI - Leishman-Giemsa Cocktail - Is it an Effective Stain for Air Dried Cytology
Smears.
AB - INTRODUCTION: Air dried cytology smears are stained routinely with Romanowsky
stains so that the relative cell size, nuclear size, cytoplasmic details, smear
background elements and intercellular matrix components are better appreciated. A
variety of modified Romanowsky stains are used in cytology. Leishman-Giemsa (LG)
cocktail is one of the new staining techniques which can be used for staining the
air dried cytology smears. AIM: To evaluate the quality of staining of LG
cocktail on air dried smears and to compare the quality of staining of LG
cocktail with May Grunwald Giemsa (MGG) which is the most commonly used stain in
cytology. MATERIALS AND METHODS: The present prospective comparative study was
carried out with 100 cases and two extra smears were prepared for each case and
stained with MGG and LG cocktail stains. The stained slides were blinded and were
evaluated for the staining characteristics of the nucleus, cytoplasm and
background staining. Based on this, scoring was done by two pathologists
independently. Quality Index (QI) was calculated by dividing the scores obtained
with the total score possible. RESULTS: LG cocktail stained slides were excellent
in cytoplasmic staining, granularity, nuclear morphology, background material
staining and overall staining characteristics. QI of LG cocktail was 0.8 while
that of MGG was 0.59. CONCLUSION: Staining of air dried smears by LG cocktail has
a good QI. It is also cheaper, requires short duration for staining as compared
to MGG. Hence, LG cocktail can be an effective replacement for MGG for staining
the air dried cytology smears.
PMID- 28511389
TI - Variability of Iron Load in Patients of Sickle Cell Anaemia (HbSS): A study from
Eastern India.
AB - INTRODUCTION: Sickle Cell Anaemia (SCA) is one of the commonest
haemoglobinopathies due to a point mutation (A->T) of the beta-globin gene. Out
of five haplotypes, the Arab-Indian haplotype present in India is one of the
least severe phenotype and least studied also. It is characterized by lifelong
haemolytic anaemia requiring red cell transfusion leading to iron overload. In
contrast, there is very high incidence of deficiency of iron, folic acid and
vitamin B12. AIM: Our objective was to access the Iron status of SCA patients and
to find its correlation with various parameters like red cell transfusion,
haemolysis and serum hepcidin. MATERIALS AND METHODS: This was a cross-sectional
study conducted on 208 patients for a period of five years. Complete Blood Count
(CBC), iron profile, haemolytic parameters and transfusion requirement were
studied and data compared with 52 healthy controls. RESULTS: Few patients (9.6%)
revealed significant iron overload (Serum ferritin > 1000 ng/ml). In majority
(80.8%) it was either normal or border line raised (300 to 1000 ng/ml) or iron
deficiency was noted in a small fraction (9.6%). Frequency of transfusion is the
principal factor which positively correlated with level of iron load (p<0.001)
while parameters of haemolysis and serum hepcidin level play an insignificant
role in this context (p= 0.0634). CONCLUSION: This study supports the notion that
the presentation of SCA patients in India is of "Viscosity - Vaso-Occlusive
Crisis (VOC) phenotype" with high incidence of VOC, low haemolytic rate and
transfusion requirement. Iron deficiency may be present in SCA patients requiring
Iron supplementation. We suggest further studies to establish the role of
hepcidin, ferroportin and other factors that control iron absorption in these
patients.
PMID- 28511390
TI - Expression of Angiogenic Factors in Psoriasis Vulgaris.
AB - INTRODUCTION: Psoriasis is a chronic inflammatory skin disease characterized by
epidermal hyperproliferation, abnormal differentiation and inflammatory
infiltration in the dermis. The dermal microvascular expansion associated with
abnormal orientation and dilatation of capillaries in the biopsies of the
psoriatic skin suggest that the disease is dependent on angiogenesis. AIM: To
analyze and compare the immunohistochemical expression of angiogenic factors -
Vascular Endothelial Growth Factor (VEGF), von Willebrand Factor (vWF) and CD 34
in skin biopsies of psoriasis cases with control skin samples; and to correlate
the expression of angiogenic factors with Psoriasis Area and Severity Clinical
Index (PASI SCORE). MATERIALS AND METHODS: This was a prospective case control
study conducted over a period of 15 months. Thirty-two psoriasis cases and thirty
control skin samples were included in the study. Skin biopsy specimen was taken
from clinically diagnosed psoriasis cases who did not receive any treatment. The
diagnosis of psoriasis vulgaris was confirmed after microscopic examination.
Immunohistochemical expression for VEGF, vWF and CD 34 was studied. RESULTS: VEGF
expression in epidermis was significantly higher in cases when compared to
control skin (p <0.01). CD 34 expression was significantly upregulated in cases
when compared to controls (p<0.01). Von Willebrand factor expression was weak in
both the cases and the controls. Significant correlation between the expression
of VEGF and PASI score (r=0.944; p<0.01), and expression of CD 34 and PASI score
was observed (r=0.942; p<0.01). CONCLUSION: In the present study, significant
overexpression of VEGF and CD 34 was noted in cases when compared to controls.
The keratinocytes in the psoriatic skin lesions were recognized as a source of
pro-angiogenic cytokines namely the VEGF and other growth factors which promotes
angiogenesis in psoriatic plaque. Angiogenesis plays an important role in genesis
and development of psoriasis vulgaris. Therefore, development of targeted anti
angiogenic therapy might be beneficial for this chronic disabling dermatological
disease.
PMID- 28511391
TI - Utility of Modified Ultrafast Papanicolaou Stain in Cytological Diagnosis.
AB - INTRODUCTION: Need for minimal turnaround time for assessing Fine Needle
Aspiration Cytology (FNAC) has encouraged innovations in staining techniques that
require lesser staining time with unequivocal cell morphology. The standard
protocol for conventional Papanicolaou (PAP) stain requires about 40 minutes. To
overcome this, Ultrafast Papanicolaou (UFP) stain was introduced which reduces
staining time to 90 seconds and also enhances the quality. However, reagents
required for this were not easily available hence, Modified Ultrafast
Papanicolaou (MUFP) stain was introduced subsequently. AIM: To assess the
efficacy of MUFP staining by comparing the quality of MUFP stain with
conventional PAP stain. MATERIALS AND METHODS: FNAC procedure was performed by
using 10 ml disposable syringe and 22-23 G needle. Total 131 FNAC cases were
studied which were lymph node (30), thyroid (38), breast (22), skin and soft
tissue (24), salivary gland (11) and visceral organs (6). Two smears were
prepared and stained by MUFP and conventional PAP stain. Scores were given on
four parameters: background of smears, overall staining pattern, cell morphology
and nuclear staining. Quality Index (QI) was calculated from ratio of total score
achieved to maximum score possible. Statistical analysis using chi square test
was applied to each of the four parameters before obtaining the QI in both
stains. Students t-test was applied to evaluate the efficacy of MUFP in
comparison with conventional PAP stain. RESULTS: The QI of MUFP for thyroid,
breast, lymph node, skin and soft tissue, salivary gland and visceral organs was
0.89, 0.85, 0.89, 0.83, 0.92, and 0.78 respectively. Compared to conventional PAP
stain QI of MUFP smears was better in all except visceral organ cases and was
statistically significant. MUFP showed clear red blood cell background,
transparent cytoplasm and crisp nuclear features. CONCLUSION: MUFP is fast,
reliable and can be done with locally available reagents with unequivocal
morphology which is the need of the hour for a cytopathology set-up.
PMID- 28511392
TI - The Diagnostic Value of Urine Lipoarabinomannan (LAM) Antigen in Childhood
Tuberculosis.
AB - INTRODUCTION: Diagnosis of Tuberculosis (TB) in children is difficult because the
clinical presentation is not specific, the chest X-ray interpretation has low
accuracy and sputum sample is difficult to obtain. Antigen detection test such as
rapid urine LAM is a non-invasive alternative for diagnosing TB .
Lipoarabinomannan (LAM) is the main component of M.tuberculosis cell wall. AIM:
To determine the diagnostic value of urinary LAM antigen for diagnosis of
childhood TB. MATERIALS AND METHODS: In the present cross-sectional study,
subjects were included using consecutive sampling method. All the children aged 0
14 years Suspected of pulmonary or extra pulmonary TB suffering from cough more
than two weeks, fever without clear aetiology, loss of body weight or poor weight
gain, fatigue, malaise, chronic lymph node enlargement, spine angulation, joint
swelling and had history of contact with positive sputum smear adult TB patient
were enrolled in the study. Pulmonary and extra pulmonary diagnosis was based on
clinical presentation, Tuberculin Skin Test (TST), chest X-ray, Acid Fast
Bacillus (AFB) staining and or sputum culture. Urinary LAM level was measured by
using Enzyme-Linked Immunosorbent Assay (ELISA). Cut off value and Area Under the
Curve (AUC) were determined using ROC statistical analysis (SPSS 21.0).
Sensitivity and specificity was measured from 2x2 cross table. RESULTS: Out of 61
subjects suspected as TB, 49 (80.3%) were eventually diagnosed with TB. Of those
diagnosed with TB, 21 (42.9%) were microbiologically confirmed cases either by
sputum microscopy (34.7%) or culture (8.2%), whereas 28 subjects were unconfirmed
cases (57.1%). The urinary LAM level was higher in subjects with TB (1.80+1.02)
mg/l compared to non-TB group (0.46+0.3) mg/l; p<0.001(independent t-test). Urine
LAM had 83% sensitivity and 85% specificity with cut off value 0.98 mg/l using
microbiological and clinical confirmation as standard reference and 33%
sensitivity and 60% specificity with cut off value 1.69 mg/l using
microbiological confirmation only. CONCLUSION: Urinary LAM has good diagnostic
value for childhood TB diagnosis.
PMID- 28511393
TI - Utility of Tru-Cut Biopsy of Breast Lesions - An Experience in a Regional Cancer
Center of a Developing Country.
AB - INTRODUCTION: Tru-cut Needle Biopsy (TCB) is an integral part of triple
assessment of breast cancer, which includes clinical assessment, mammography and
TCB or Core Needle Biopsy (CNB). The technique is reliable, simple, and
reproducible, and inexpensive, which can be adapted even for low-income group of
patients and in developing countries. AIM: This study was done to establish the
efficacy of TCB of palpable breast lesions in a developing country where
mammography is not possible in all cases. MATERIALS AND METHODS: A retrospective
analysis of 892 TCBs was done in AH Regional Cancer Centre, Cuttack, Odisha,
India where TCBs were performed in patients presenting to outpatient department
with palpable breast lesions. The H&E stained sections were interpreted by
pathologists of the same centre. Diagnosis was classified into different
categories. Immunohistochemistry (IHC) for Estrogen Receptor (ER), Progesterone
Receptor (PR) and Her-2/neu was done and interpreted by Allred scoring system.
RESULTS: A total 892 TCBs were analysed with 23 repeat TCBs. There were 13 (1.4%)
male patients. A total of 747 cases (83.6%) were diagnosed as malignant,
including 735 carcinomas, nine malignant phyllodes tumour, two angiosarcoma and
one case of Non-Hodgkin' Lymphoma (NHL). It was possible to diagnose special
histological types such as lobular carcinoma, metaplastic carcinoma and mucinous
carcinoma on TCB. A total of 21 cases were diagnosed as carcinoma on repeat
biopsy. Eight of the 735 TCBs diagnosed as carcinoma were bilateral breast
cancers, hence actual number of carcinoma cases were 727. IHC was done
successfully on the paraffin blocks in 260 cases. In this series out of 727
patients of carcinomas 30% were in young, i.e., below 40 years of age, including
four cases of carcinoma below 20 years. There were no false positive case in this
study giving a specificity of 100% and sensitivity was 97%. CONCLUSION: TCBs are
well tolerated by patients, can be done in OPDs and reduce cost. It is possible
to give histological diagnosis of carcinoma, lymphoma, phyllodes tumour and
sarcomas on TCBs. The paraffin blocks of TCBs can be used for IHC study which
helps the oncologists for preoperative adjuvant therapy.
PMID- 28511394
TI - Breast Biomarkers-Comparison on Whole Section and Tissue Microarray Section.
AB - INTRODUCTION: Estrogen Receptor (ER), Progesterone Receptor (PR) and Her2/neu are
routinely studied markers for breast carcinoma. Analysis of these biomarkers is
traditionally done by Immunohistochemistry (IHC) on whole sections. These markers
can also be studied on Tissue Microarray (TMA) sections. Tissue microarray is a
technique where core samples from different paraffin blocks are arrayed on a
single recipient block which can then be cut to yield a single section with
multiple cores in it. AIM: To compare ER, PR and Her2/neu on TMA sections with
whole sections and to determine the concordance of results between the two
methods. MATERIALS AND METHODS: A TMA block was constructed by punching out 2 mm
cores from appropriately marked paraffin blocks of 53 breast carcinoma cases and
embedding them in the recipient block. Immunostaining of TMA sections and whole
sections were performed for ER, PR and Her2/neu and the results were compared.
Statistical analysis was done using chi square test/Fisher-Exact test. Kappa co
efficient, Jaccard Index and G-Index were computed. RESULTS: Infiltrating Ductal
Carcinoma-No Special Type (IDC-NST) was the predominant type of carcinoma and
most of the tumours were of Grade II and III. Majority, 38/53 (71.7%) were ER/PR
positive and Her2 negative and 9/53 (17%) cases were triple negative. Good
concordance between whole sections and TMA sections were noted with kappa value
for ER, PR and Her2/neu being 0.671, 0.754, 1.000 respectively which was
statistically significant. CONCLUSION: Immunostaining for ER, PR and Her2/neu
done on TMA section using single 2 mm core were comparable with conventional
whole section scores. Thus, TMA is a reliable method for evaluating these
biomarkers with the advantage of being time and cost effective.
PMID- 28511395
TI - Clinical and Cytological Spectrum of Granulomatous Mastitis and Utility of FNAC
in Picking up Tubercular Mastitis: An Eight-Year Study.
AB - INTRODUCTION: Granulomatous Mastitis (GM) is a rare, benign, inflammatory disease
of the breast. It is a well known mimicker of malignancy, clinically and
radiologically. Patients are often subjected to number of tests for the right
diagnosis. Non-specific Granulomatous Mastitis (NGM) and Tubercular Mastitis
(TBM) are chief among the various causes of GM. They are important to be
diagnosed early as their treatment varies significantly. Fine Needle Aspiration
Cytology (FNAC) is simple, patient friendly and primary investigation modality in
cases of lump in breast. AIM: To find out the utility of FNAC in differentiating
NGM and TBM. MATERIALS AND METHODS: All cases of granulomatous mastitis diagnosed
on cytology over eight years were retrospectively retrieved. The clinical and
radiological history was obtained from the patient file. The slides were stained
with haematoxylin and eosin stain as well as Leishman stains. Special stains like
Periodic Acid Schiff (PAS) and Ziehl Neelsen (ZN) stain were used for fungus and
Mycobacteriumtuberculosis respectively. Histopathological correlation of the
available cases was done. Clinical presentation and cytological morphology of
individual cases was studied in detail. RESULTS: Twenty one cases of GM obtained,
of which 16 were NGM and five were TBM. Both diseases were common among young
reproductive women who presented with unilateral breast lump of varying duration.
Almost 25% of NGM and 60% of TBM has clinical suspicion of malignancy. About 30%
had radiological suspicion of malignancy. Nearly 62.5% of NGM patients had
painful swelling and none of tubercular mastitis patients had pain. About 31% of
NGM patients underwent prior abscess drainage and 40% of TBM patients gave
history of tuberculosis. Almost 6.25% of NGM and 60% of TBM had axillary
lymphadenopathy. Cytologically epithelioid cells were identified in 100% of
patients whereas, granulomas were seen in 62.5% and 80% of NGM and TBM smears
respectively. Langhans giant cells were frequent among TBM and foreign body giant
cell among NGM. Caseous necrosis was seen in 60% of TBM and absent in NGM smears.
CONCLUSION: Though, NGM and TBM is said to have overlapping features, our study
highlights few clinical and cytological differences which aid in differentiating
the two entities at primary level. FNAC along with special stain must be
advocated as the primary tool of diagnosis in cases of GM.
PMID- 28511396
TI - A Clinicopathological Study of Paediatric Liver Tumours in a Tertiary Care
Hospital.
AB - INTRODUCTION: Paediatric primary liver tumours are the third largest group of
solid abdominal neoplasms in children next to neuroblastoma and Wilms tumour,
accounting for about 0.5% to 2% of all paediatric neoplasms, in which
hepatoblastoma is the most common. AIM: The present study was done to estimate
the incidence of paediatric liver tumours over a period of five years and also,
to study the clinical behaviour, alpha-fetoprotein correlation and
histopathological features of paediatric liver tumours. MATERIALS AND METHODS:
The details of patients treated for paediatric liver tumours for a period of five
years were retrospectively retrieved from the tumour board and medical records.
The gross features and all the slides were reviewed and the pathologic diagnosis
was confirmed and clinicopathological correlation was then done. RESULTS: A total
of 39 paediatric liver tumours were detected during five years, of which 32 (82%)
were malignant and seven (18%) were benign with a male to female ratio of 1:1.1.
Hepatoblastoma was the most common liver tumour accounting for 28 cases (71.8%),
of which 25 cases (89.4%) were of pure epithelial type. The second most common
primary tumour was epithelioid haemangioendothelioma with six cases (15.4%) with
female preponderance, followed by two cases each of hepatocellular carcinoma and
undifferentiated embryonal sarcoma and one case of hepatocellular adenoma. Serum
AFP level was increased in hepatoblastoma and in hepatocellular carcinoma, normal
in hepatocellular adenoma and embryonal sarcoma. Serum AFP level was increased in
few cases of epithelioid haemangioendothelioma. CONCLUSION: The spectrum of liver
tumours in children is different from that in the adults. Hepatoblastoma is the
most common paediatric liver tumour, followed by epithelioid
haemangioendothelioma. Through better understanding of pathological diagnosis,
refined surgical staging, newer and more effective radiological techniques and
standardized multimodal therapies, a substantial number of children diagnosed
with this highly malignant tumour can expect to survive the disease.
PMID- 28511397
TI - Fibroadenoma in Axillary Ectopic Breast Tissue Mimicking Lymphadenopathy.
AB - Swellings in the axilla especially in women are always viewed with suspicion
owing to a large number of these being associated with breast carcinoma
presenting as nodal metastasis. In a country like India, tuberculous
lymphadenopathy is also amongst the first differentials. We present a case of a
woman with right sided axillary swelling mimicking lymphadenopathy which on Fine
Needle Aspiration Cytology (FNAC) turned out to be fibroadenoma of the ectopic
breast tissue. This condition is a rare occurrence in Ectopic Breast Tissue (EBT)
as opposed to that in the normal breast, the most common pathology affecting
ectopic breast being carcinomas.
PMID- 28511398
TI - Undifferentiated Uterine Sarcoma: An Uncommon Case Report.
AB - Endometrial Stromal Sarcomas (ESS) are rare uterine malignancy of mesodermal
origin. A 65-year-old female presented with postmenopausal bleeding in the
Department of Gynaecology in our hospital. Computed Topography (CT) revealed an
enlarged uterus with areas of low attenuation. On gross appearance endometrial
cavity was distorted with an irregular friable necrotic mass.
Histopathologically, it was diagnosed as undifferentiated uterine sarcoma.
Rhabdoid, osteoid and cartilaginous differentiation were found along with
osteoclast like giant cells. Immunohistochemistry was strongly positive for CD10.
PMID- 28511399
TI - Primary Ovarian Endometrioid Stromal Sarcoma Presenting with Infertility.
AB - Endometrioid Stromal Sarcoma (ESS) is an uncommon tumour that occurs in women
over wide age range of 11 years to 76 years accounting for only 0.2% of all
uterine malignancies and for 15%-26% of primary uterine sarcomas. These tumours
arising from ovary are extremely rare. Most of them are associated with
nulliparous or perimenopausal women. It is commonly associated with endometriosis
of the ovary. Here we present this rare case to emphasize on the uniqueness and
histomorphology of ovarian ESS in patients with endometriosis.
PMID- 28511400
TI - A Case Report of a Giant Cholesteatoma.
AB - Cholesteatoma is a well demarcated, non-neoplastic, temporal bone cystic lesion
with extensive keratinisation. Keratoma and epidermoid cyst are other possibly
more accurate names suggested to describe the same. It can be classified as
congenital or acquired. Its management is often complicated by its tendency to
recidivism/recurrence. Long standing cholesteatomas can be a precursor for
squamous cell carcinoma. We hereby present a case of giant cholesteatoma in a 45
year-old female with radiological involvement of the left temporal region,
periauricular region and infratemporal fossa with lytic destruction of left
middle ear ossicles, mastoid and squamous part of temporal bone with intracranial
extension. The enormity of the present lesion along with its bony erosions raised
the strong clinical suspicion of malignancy. The underlying case report
highlights the relevance of exhaustive sectioning and immunohistochemistry to
reach the diagnosis.
PMID- 28511401
TI - Jejunal Gastric Heterotopia causing Multiple Strictures and Perforation
Peritonitis- A Case Report with Review of Literature.
AB - Gastric heterotopias beyond the ligament of Treitz though rare, should be thought
of in the differential diagnosis of polypoid lesions presenting with
gastrointestinal bleed or obstructive symptoms especially in children and in the
young. Here is a 24-year-old male with multifocal jejunal gastric heterotopias
causing multiple strictures and perforation peritonitis. Patient presented with
acute abdomen pain and an emergency laparotomy was performed revealing jejunum
with multiple strictures and perforation, followed by jejunal resection. On gross
examination polypoid mucosa was noted at the stricture sites which showed
heterotopic gastric mucosa on microscopy. Jejunal gastric heterotopias are
extremely rare with less than ten reported cases and those presenting with
multiple strictures are even rarer. To our knowledge this is the second case of
jejunal gastric heterotopia presenting with multiple strictures.
PMID- 28511402
TI - Bladder Adenocarcinoma: A Persisting Diagnostic Dilemma.
AB - Primary urinary Bladder Adenocarcinoma (PBA) is an uncommon neoplasm and can
cause diagnostic difficulties due to histologic similarities with adenocarcinomas
of adjacent structures like Gastrointestinal Tract (GIT) and prostate, since
involvement of the bladder by metastasis or direct spread can occur. Seven cases
of bladder adenocarcinomas were diagnosed during a period of four years in a
tertiary care hospital. Patient's age ranged from 26-78 years with a male
predilection. Three cases were signet ring type adenocarcinomas, two cases were
subtyped as enteric variant, one as mucinous variant and one as adenocarcinoma
Not Otherwise Specified (NOS) variant. One case showed urachal involvement.
Common site of involvement was the base and posterior wall of the bladder. Three
cases had prior history of GIT malignancy. No morphologic difference was
identified to differentiate primary from secondary adenocarcinomas. Bladder
adenocarcinoma is rare tumours. Primary and secondary adenocarcinomas cannot be
distinguished from each other on morphologic grounds. Ancillary studies may have
limited role in distinguishing between the two. Hence, clinical correlation has a
major role in their evaluation.
PMID- 28511403
TI - A Prospective Analysis of Drug Interactions in Patients of Intensive Cardiac Care
Unit.
AB - INTRODUCTION: Drug-Drug Interaction (DDI) is a serious concern in cardiac
patients due to polypharmacy. AIM: The present study was aimed to identify the
potential DDI among hospitalized cardiac patients and evaluate the mechanism and
severity of such interactions. MATERIALS AND METHODS: A prospective observational
study was conducted in intensive cardiac care unit of a tertiary care hospital
for six months. Patients aged 18 years and above and taking two or more drugs
were included in the study. Medscape drug interaction checker was used to
identify and analyze the pattern of potential DDI. RESULTS: Out of 500 patients,
most of the patients were male (78.4%) in the age group of 50-60 years (31%). The
most common diagnosis was acute coronary syndrome (57.2%). Out of total 2849 DDI,
2194 (77.01%) were pharmacodynamic, 586 (20.57%) were pharmacokinetic in nature
while 69 (2.42%) drug pairs interacted by unknown mechanism. Majority of drug
interactions were significant {2031 (71.29%)} in nature followed by minor
{725(25.45%)} while serious drug interactions were observed in only 93 (3.26%)
drug pairs. A positive correlation was observed between patient's age and number
of drugs prescribed (r=0.178, p<0.001), number of drugs prescribed and potential
Drug-Drug Interaction (pDDI) (r= 0.788, p<0.001) and between patient's age and
pDDI (r=0.338, p<0.001). CONCLUSION: The risk of pDDI was more commonly observed
in elderly male patients particularly with antiplatelet drugs like low dose
aspirin and clopidogrel.
PMID- 28511404
TI - Statin Induced Rhabdomyolysis with Non Oliguric Renal Failure: A Rare
Presentation.
AB - Statins are safe, well tolerated, efficient and time tested drugs for the
management of hypercholesterolemia, and thus play a cardinal role in the
management of patients with heart disease. Although safe in clinical practice,
they are associated with adverse effects, clinically the most important and most
severe being muscle related complications/myotoxicity. Rhabdomyolysis, though
rare, is the most severe form of myotoxicity. The US Food and Drug Administration
(USFDA) adverse event reporting system reports rate of statin induced
rhabdomyolysis at 0.3-13.5 cases per 1,000,000 patients. We present a case of a
74-year-old male who presented with an acute coronary syndrome and was initiated
on atorvastatin. However, patient developed atorvastatin induced rhabdomyolysis,
with non oliguric renal failure, which subsequently improved on cessation of
medication.
PMID- 28511405
TI - Evaluation of Acute Oral Toxicity of Ethanol Leaves Extract of Catharanthus
roseus in Wistar Albino Rats.
AB - INTRODUCTION: Herbal drugs have gained importance globally in the treatment of
various diseases. Catharanthus roseus is traditionally used as an anti diabetic
and anti cancer drug. To the best of our knowledge limited data are available on
acute and sub acute toxicity of C. roseus extract despite its wide spread use in
traditional medicine. The present study was under taken to evaluate the acute
oral toxicity of the ethanol leaves extract of C. roseus. AIM: To investigate the
acute oral toxic effects of ethanol leaves extract of C. roseus. The objective of
the study was to evaluate organ toxicity related to heart, liver and kidney in
wistar albino rats. MATERIALS AND METHODS: The experiment was done based on the
Organization for Economic Co-operation and Development (OECD) guideline 420. The
study included twenty five non pregnant female wistar rats (n=25). Sighting study
was done using the fixed dose method. The study was conducted by giving a single
dose of test drug varying from 5, 50, 300 and 2000 mg and animals were observed
for fourteen days. Blood samples were collected and biochemical findings SGPT,
SGOT, urea, creatinine, creatinine phosphokinase and Lactate Dehydrogenase (LDH)
were analyzed. Food consumption, water intake and histopathology changes were
evaluated. RESULTS: Catharanthus roseus Extract (CRE) at a dose of 2000 mg did
not produce mortality. SGOT, SGPT, Creatinine phosphokinase, LDH, urea and
creatinine were elevated in 300 mg and 2000 mg doses. CONCLUSION: Though there
was no mortality, the extract of C. roseus higher than 300 mg can produce signs
of biochemical and histopathological toxicity in liver, kidney and heart. It is
recommended that lower doses than the studied ones should be used for treatment.
PMID- 28511406
TI - Effect of Sodium Valproate and Docosahexaenoic Acid on Pain in Rats.
AB - INTRODUCTION: Analgesics are commonly prescribed medications used to alleviate
pain of various aetiologies without affecting the patient's consciousness. They
interfere with the transmission of pain signals. A commonly used antiepileptic
drug, sodium valproate has been used in various non-epileptic conditions like
migraine prophylaxis and in the treatment of bipolar disorder because of the
multiple mechanisms by which it acts. Docosahexanoic Acid (DHA), an omega 3 fatty
acid, is known to possess analgesic activity. We planned a study to assess the
effect of sodium valproate alone and in combination with DHA in rat models of
pain. AIM: To evaluate the analgesic activity of sodium valproate and DHA
supplementation using various experimental models in albino Wistar rats.
MATERIALS AND METHODS: For analgesic activity, A total of 48 adult Wistar albino
rats were divided into eight groups of six rats each. Group I was control (distil
water 1 ml/kg), Group II received intraperitoneal injection of tramadol (10
mg/kg), Group III, IV, V were injected intraperitoneal sodium valproate 100, 200,
400 mg/kg with distil water respectively and Group VI, VII, VIII were given
sodium valproate 100, 200, 400 mg/kg plus DHA 300 mg/kg (intraperitoneal)
respectively. Analgesic activity was assessed using hot plate, tail flick and
acetic acid writhing models. RESULTS: We found that sodium valproate at higher
doses (400 mg/kg) used either alone along with DHA (300 mg/kg) showed
statistically significant analgesic activity in comparison to control in various
experimental models for assessing pain. CONCLUSION: Combination of sodium
valproate along with DHA has shown promising analgesic activity.
PMID- 28511407
TI - Gerbode Ventricular Septal Defect -A Rare Cardiac Anomaly Associated with Genetic
Variants in Indian Population- A Case Series.
AB - Gerbode defects are rare Ventricular Septal Defects (VSD) constituting
approximately one percent cases of congenital heart diseases. The genetic
predispositions towards the Gerbode Defect (GD) have remained an unexplored area
of study till date. We investigated the genotype-phenotype correlation in
patients with Gerbode VSD. Molecular genetic study on Sanger sequencing and
subsequent data analysis showed that the contributing sequence variations in the
NKX2-5, GATA4 and TBX5 gene lies in one of the highly conserved regions and this
region is responsible for encoding a functional protein. The resulting genotype
variation may be responsible for causing the diseased phenotype known as GD.
PMID- 28511408
TI - Estimation of Total Length of Femur from its Proximal and Distal Segmental
Measurements of Disarticulated Femur Bones of Nepalese Population using
Regression Equation Method.
AB - INTRODUCTION: Length of long bones is taken as an important contributor for
estimating one of the four elements of forensic anthropology i.e., stature of the
individual. Since physical characteristics of the individual differ among
different groups of population, population specific studies are needed for
estimating the total length of femur from its segment measurements. AIM: Since
femur is not always recovered intact in forensic cases, it was the aim of this
study to derive regression equations from measurements of proximal and distal
fragments in Nepalese population. MATERIALS AND METHODS: A cross-sectional study
was done among 60 dry femora (30 from each side) without sex determination in
anthropometry laboratory. Along with maximum femoral length, four proximal and
four distal segmental measurements were measured following the standard method
with the help of osteometric board, measuring tape and digital Vernier's caliper.
Bones with gross defects were excluded from the study. Measured values were
recorded separately for right and left side. Statistical Package for Social
Science (SPSS version 11.5) was used for statistical analysis. RESULTS: The value
of segmental measurements were different between right and left side but
statistical difference was not significant except for depth of medial condyle
(p=0.02). All the measurements were positively correlated and found to have
linear relationship with the femoral length. CONCLUSION: With the help of
regression equation, femoral length can be calculated from the segmental
measurements; and then femoral length can be used to calculate the stature of the
individual. The data collected may contribute in the analysis of forensic bone
remains in study population.
PMID- 28511409
TI - Knowledge, Attitude and Practice of Healthcare Managers to Medical Waste
Management and Occupational Safety Practices: Findings from Southeast Nigeria.
AB - INTRODUCTION: Awareness of appropriate waste management procedures and
occupational safety measures is fundamental to achieving a safe work environment,
and ensuring patient and staff safety. AIM: This study was conducted to assess
the attitude of healthcare managers to medical waste management and occupational
safety practices. MATERIALS AND METHODS: This was a cross-sectional study
conducted among 54 hospital administrators in Ebonyi state. Semi-structured
questionnaires were used for qualitative data collection and analyzed with SPSS
statistics for windows (2011), version 20.0 statistical software (Armonk, NY: IBM
Corp). RESULTS: Two-fifth (40%) of healthcare managers had received training on
medical waste management and occupational safety. Standard operating procedure of
waste disposal was practiced by only one hospital (1.9%), while 98.1% (53/54)
practiced indiscriminate waste disposal. Injection safety boxes were widely
available in all health facilities, nevertheless, the use of incinerators and
waste treatment was practiced by 1.9% (1/54) facility. However, 40.7% (22/54) and
59.3% (32/54) of respondents trained their staff and organize safety orientation
courses respectively. Staff insurance cover was offered by just one hospital
(1.9%), while none of the hospitals had compensation package for occupational
hazard victims. Over half (55.6%; 30/54) of the respondents provided both
personal protective equipment and post exposure prophylaxis for HIV. CONCLUSION:
There was high level of non-compliance to standard medical waste management
procedures, and lack of training on occupational safety measures. Relevant
regulating agencies should step up efforts at monitoring and regulation of
healthcare activities and ensure staff training on safe handling and disposal of
hospital waste.
PMID- 28511412
TI - Regulation of Molecular Diagnostic (NAT) Kits For HBV, HCV and HIV in India.
PMID- 28511410
TI - Preventive Training among Medical Interns in Mexico City and Its Association with
Needlestick and Sharp Injuries - A Cross Sectional Study.
AB - INTRODUCTION: Medical students are a vulnerable group for the acquisition of
blood borne pathogens due to their lack of experience. In Europe and Asia
preventive training programs have reduced accidental exposures. AIM: The aim of
the study was to compare the lifetime prevalence of Needlestick and Sharp Objects
Injuries (NSIs) among medical interns who received preventive training versus
those without such training in Mexico City. MATERIALS AND METHODS: In 2013, a
cross-sectional study was performed applying an anonymous self-administrated
questionnaire. The study population included 467 medical students, male and
female, at the end of their internship. The lifetime prevalence of NSI was
estimated and compared between students who had received preventive training and
those who did not. RESULTS: The overall lifetime prevalence of NSI was 58%.
Lifetime prevalence was higher in students without preventive training compared
to those who had such a training (68% vs 51%; p value= 0.002). NSI Lifetime
prevalence was not associated with sex, age or place of birth. The task most
commonly associated with the latest NSI in trained and untrained students was
withdrawing blood. CONCLUSION: NSI are frequent accidents among medical students
in Mexico City, especially during blood taking. Training units on how to prevent
NSI should be encouraged in Mexican medical colleges.
PMID- 28511411
TI - Relationship of Lifestyle with Academic Achievement in Nursing Students.
AB - INTRODUCTION: A healthy lifestyle is one of the main factor in maintaining the
health of people in society. With regard to the role of youth and students in
public health, they must complete and follow a training program on lifestyle
related factors. One of the main aim of the training centres is to improve the
academic achievement of students. AIM: This study was designed to determine the
correlation of lifestyle with academic achievement in nursing students. MATERIALS
AND METHODS: This was a cross-sectional study, wherein all nursing students of
School of Borujen Nursing were selected by census sampling. Data gathering tool
was Walker's lifestyle questionnaire which was modified for the purpose of the
study. To evaluate the educational status of students, final grade point average
was considered as an indicator of academic achievement. To analyze the data, SPSS
version 16.0, and descriptive and analytical tests were used. RESULTS: The
results indicated that most subjects (61.01%) displayed moderate levels of
lifestyle. Pearson's correlation coefficient showed the significant positive
relationship between lifestyle and academic achievement (p=0.03 and r=0.628).
CONCLUSION: To improve the academic achievement of students, in addition to the
cognitive abilities-perception, their lifestyle should also be considered.
Therefore, it is suggested to incorporate lifestyle education in the curriculum
of nursing students so as to improve their lifestyle.
PMID- 28511413
TI - Knowledge Attitude and Perception of Sex Education among School Going Adolescents
in Ambala District, Haryana, India: A Cross-Sectional Study.
AB - INTRODUCTION: Adolescence is a highly dynamic period characterised by rapid
growth and development. Adolescents have limited knowledge about sexual and
reproduction health, and know little about the natural processes of puberty,
sexual health, pregnancy or reproduction. Sex education should be an integral
part of the learning process beginning in childhood and continuing into adult
life, because it is lifelong process. AIM: This study was carried out to identify
the knowledge and attitude of imparting sex education in school going adolescents
in rural and urban area of Ambala district. MATERIALS AND METHODS: A cross
sectional study design was used to study the knowledge of reproductive and sexual
health among school going children. A total of 743 adolescents from age group of
13-19 year were studied, using self designed semi-structured questionnaire to
assess the knowledge regarding reproductive and sexual health among adolescents.
RESULTS: The mean age of study subjects was 15.958+/-1.61 years, majority of
adolescents i.e., 93.5% favour sex education. An 86.3% said sex education can
prevent the occurrence of AIDS and 91.5% of adolescents prefer doctors should
give them sex education followed by 83.0% school/teacher and least preference was
parents 37.3%. CONCLUSION: There were substantial lacunae in the knowledge about
reproductive and sexual health. Students felt that sex education is necessary and
should be introduced in the school curriculum.
PMID- 28511414
TI - A Community Based Study on Pelvic Inflammatory Disease in Postmenopausal Females:
Microbiological Spectrum and Socio-Demographic Correlates.
AB - INTRODUCTION: Pelvic Inflammatory Disease (PID) is a common and serious
complication of sexually transmitted diseases in young women but is rarely
diagnosed in the postmenopausal women. Very few studies have been done regarding
post-menopausal PID. AIM: To determine the burden of PID, associated micro
organisms, pathophysiology and risk factors among post-menopausal women of the
community. MATERIALS AND METHODS: A cross-sectional study was conducted among 530
post-menopausal women in the registered field practice areas of the JN Medical
College and Hospital, Aligarh, Uttar Pradesh, India. A pre designed and pre
tested proforma was used to obtain data regarding socio-demographic details and
factors associated with PID. Clinical and laboratory examinations were done to
confirm the diagnosis of PID. Data was analyzed using SPSS 23.0. Association
between categorical variables was tested with chi-square test and logistic
regression analysis was used to find independent risk factors. The value of
p<0.05 was considered as significant. RESULTS: About 11.55% of the study subjects
were diagnosed with PID (12.5% in rural areas and 10.6% in urban areas).
Bacterial vaginosis followed by Trichomonas vaginalis were most common. Among the
important risk factors, significant association was found with occupation of the
women, increasing parity, multiple sexual contacts, and associated pelvic organ
prolapse. Association with smoking, chronic illnesses, diabetes mellitus and
hypertension, and associated urinary tract infection were not found to be
significant. CONCLUSION: The study shows the hidden burden of the disease in the
community and the associated risk factors, which can be prevented by life style
and cultural changes if incorporated earlier in the lives.
PMID- 28511415
TI - Impact of a Structured Tuberculosis Awareness Strategy on the Knowledge and
Behaviour of the Families in a Slum Area in Chhattisgarh, India.
AB - INTRODUCTION: Of different methods of disease prevention, health education and
awareness programmes can empower people regarding several aspects of disease
management and thereby enabling them in accessing the right treatment, in right
time, at right place. AIM: The aim of this study was to assess the impact of a
structured Tuberculosis (TB) awareness strategy on the knowledge and behaviour of
slum dwellers of Durg, Chhattisgarh, India. MATERIALS AND METHODS: A TB awareness
intervention was implemented in terms of informing the houses of marginalized and
vulnerable communities about TB, its symptoms, diagnosis, treatment and Revised
National TB Control Program (RNTCP) services and the impact of the same was
assessed through a survey questionnaire before and after the implementation of
the intervention. RESULTS: Of the knowledge components the improvement was
incurred above 90% among the study participants in all components except in two
components such as; modes of TB transmission and availability of free treatment
facilities. In the behavioural segment, after the implementation of the awareness
strategy, 53% and 92% of the respondents reported to visit government health
facility for seeking help for their general and TB related problems respectively.
Similarly the responses regarding not approaching the government health facility
for TB care were changed after the implementation of the awareness strategy and
36% of the respondents said they would prefer to visit government health facility
for TB care. CONCLUSION: Health education activities should be directed to
improve the knowledge of slum dwellers regarding the modes of TB transmission and
availability of free treatment at public health facilities.
PMID- 28511416
TI - Correlation of Cotinine Levels with Use of Smokeless Tobacco (Mishri) among
Pregnant Women and Anthropometry of Newborn.
AB - INTRODUCTION: 'Smokeless tobacco' is the term used for the tobacco that is
consumed in un-burnt form and it can be used orally or nasally. Cotinine, a
nicotine metabolite, is used to quantify exposure to tobacco, which readily gains
access to foetal circulation. Cotinine is invariably found in coelomic, amniotic
and foetal serum when maternal serum cotinine levels exceed 25ng/ml. AIM: To
estimate cotinine levels among pregnant women using and not using smokeless
tobacco (mishri) and to correlate cotinine level with anthropometry of newborns.
MATERIALS AND METHODS: A hospital based cohort study was conducted at Krishna
Hospital, Karad, District Satara, Maharashtra, India. Pregnant women who were
using smokeless tobacco (mishri) during pregnancy were analyzed for cotinine
levels in blood by using ELISA kit tech and correlated with anthropometry of
newborn babies and compared with non users of tobacco. RESULTS: About 480 gm
reduction in Birth weight and 6.5 cm reduction in birth length of babies born to
mishri users compared to non users of tobacco and also cotinine levels among
users were found significantly negatively correlating with anthropometric
measurement of newborn babies. CONCLUSION: A pro-active effort is essential to
educate the women about adverse effects of tobacco in general and on the
intrauterine growth of the baby in particular.
PMID- 28511417
TI - Effectiveness of A Four-Week Diet Regimen, Exercise and Psychological
Intervention for Weight Loss.
AB - INTRODUCTION: Obesity is accompanied by restriction in the quality of life and an
increased risk of morbidity and mortality. Cardiovascular, orthopedic, and
metabolic disorders are among the possible consequences. In the management of
obesity, a combination therapy that includes dietary, exercise, and behaviour
modules has proven its worth. AIM: To evaluate the effect of weight-associated
parameters, circulation associated parameters, glucose metabolism, body
composition and life quality changes within a four-week inpatient rehabilitation
program. MATERIALS AND METHODS: Fifty-two patients underwent a 4-week inpatient
rehabilitation program consisting of nutrition therapy, behavioural therapy and
exercise therapy modules at the Eleonoren Clinic of Winterkasten, Germany.
RESULTS: The mean weight reduction of 52 obese patients 40 (76.9%) males, 12
(23.1%) females; mean age 46 years; mean Body Mass Index (BMI) 43,79 kg/m2)
achieved was 7.1 kg (from 1.20 kg to 17.50 kg), and the BMI reduction was 2.3
kg/m2 (from 0.40 kg/m2 to 5.40 kg/m2). The excessive weight loss was highly
significant (p<0.001). Weight reduction was accompanied by an improvement in the
diabetic metabolic state (lowering of fasting blood-glucose 20 mg/dl,
postprandial blood glucose 26 mg/dl, HbA1c 0.27%). In all 73% of the patients
suffered from arterial hypertonia. The significant mean decline of systolic and
diastolic blood pressure was 12.8 mmHg and 6.8 mmHg, respectively. The resting
pulse was reduced by an average of 11 beats per minute. The Bioelectric Impedance
Analysis (BIA) revealed a significant reduction of body fat content (p<0.001).
The subjective impression of impaired life quality (SF-36 questionnaire) improved
significantly. CONCLUSION: The study clearly shows that the inpatient
rehabilitation program at the Eleonoren Clinic was suitable to enhance the
physical and mental state of people with obesity. In a two-year follow-up program
the patients should take care of a permanent lifestyle change toward an improved
dietary, movement and health behaviour.
PMID- 28511418
TI - Screening in Public Health and Clinical Care: Similarities and Differences in
Definitions, Types, and Aims - A Systematic Review.
AB - INTRODUCTION: The concept of screening can be many times misleading to many
people. This may be partly due to the way screening is described and explained in
textbooks and journal articles. AIM: To review prominent public health and
epidemiology textbooks, dictionaries, and relevant journal publications for
definitions and examples of screening, with the aim of identifying common usages
and concepts, as well as sources of potential confusion. MATERIALS AND METHODS:
Commonly available epidemiology and public health textbooks and peer reviewed
journals were searched for definitions and examples of screening. The search
located seven journal articles, 10 textbooks, and one dictionary. The search
platforms used were Pubmed, BIOSIS, EMBASE, Medline-OVID and Scopus under the
Epidemiology and Biostatics subject head listed with Life Sciences. RESULTS:
Descriptions of screening give varying emphasis to whether it is a test or a
program, the aims of screening, the setting in which it is conducted, eligibility
criteria, who initiates and who is intended to benefit and whether the condition
being screened is an infectious or chronic disease or a risk-elevated state. Four
essentially different 'types' of screening are described, using seven terms and
occasionally contradictory examples. The detection of asymptomatic infectious
cases is gradually changing from screening to surveillance as part of infection
control. CONCLUSION: Voluntary screening programs rely on high participation to
be effective and support and trust of the public are essential for the continued
success of the public health profession. Consistent terminology is important for
patients, providers and policymakers to understand what screening is and is not.
Clear definitions are needed if we are to evaluate and communicate the risks and
benefits of screening in public health.
PMID- 28511419
TI - Nasal NK/T Cell Lymphoma Presenting with Perforation of Palate: A Case Report and
Review of Literature.
AB - Nasal Natural Killer (NK)/T cell lymphoma, commonly mentioned in the literature
as Lethal Midline Granuloma (LMG) is an unusual pathology of the oro-maxillo
facial region characterized by aggressive and progressive destruction of the
face, nose, palate and pharynx. This disease is now classified as a T-cell
lymphoma based on modern cytogenetics, immunologic and molecular studies.
However, it is mentioned in various literatures by various names. Here, we
present one such clinically diagnosed, histopathologically and immunologically
confirmed case of LMG, designated as NK/T cell lymphoma in a 56-year-old male.
The uncommon presentation of NK/T cell lymphomas should be kept as a differential
diagnosis for management of patients.
PMID- 28511420
TI - Effect of Intraperitoneal Injection of Saffron on the Treatment of Experimental
Endotoxin Induced Uveitis in the Rabbit.
AB - INTRODUCTION: Saffron with scientific name of "Crocus sativus" from the family
"Iridaceae" is a plant without stem and root. Antioxidative and immunomodulatory
effects of saffron has been demonstrated in different studies. AIM: To assess the
effects of saffron in the treatment on Lipopolysaccharide (LPS) induced uveitis
in the rabbit. MATERIALS AND METHODS: Thirty healthy female New Zealand white
rabbits were prepared. LPS induced uveitis was confirmed via slit lamp
examination 24 hours after intravitreal injection of Salmonella typhimurium LPS
endotoxin in the right eye of all rabbits. Then the animals were randomly divided
into two equal groups - group 1 (controls) and group 2 (saffron). After 24 hours
of intravitreal injection of LPS, 60 mg/body weight of saffron was injected
intraperitoneally for Group 2. On the seventh day after intraperitoneal
injection, all rabbits of both groups were euthanized with an overdose
intraperitoneal injection of sodium thiopental. Immediately after euthanasia,
enucleation of both groups of rabbits was done. Clinical Scoring System (CSS) and
pathological severity score of uveitis was assessed for each eye. RESULTS: No
statistical difference in the CSS was found in days 3,5, and 7 after
intraperitoneal injection of saffron. Also, Pathological Severity Score (PSS) did
not show a significant difference between two groups. Additionally, the maximum
PSS of both groups was very closed but the number was observed in the saffron
group (20%) more than control group (10%). CONCLUSION: Intraperitoneal injection
of saffron was ineffective in the management of experimental uveitis. Further
studies with different dosages and follow up and using other routes of
administration are needed.
PMID- 28511421
TI - Surgical Outcome of Epicanthus and Telecanthus Correction by Double Z-Plasty and
Trans-Nasal Fixation with Prolene Suture in Blepharophimosis Syndrome.
AB - INTRODUCTION: Blepharophimosis Syndrome (BPES) is a complex and rare disease
characterized by epicanthus inversus, telecanthus, lateral ectropion, narrowed or
shortened inter-palpebral fissure distance and ptosis. It is mostly bilateral and
may or may not be symmetrical. It is typically inherited as an autosomal dominant
trait. In sporadic cases, the disease may occur without a prior family history as
a genetic mutation from a deletion or translocation of the FOXL2 gene, which maps
to chromosome 3q23. Surgical treatment of this disease poses an oculoplastic
challenge due to multiple complex eyelid deformities. AIM: To evaluate the
functional and cosmetic outcome of telecanthus and epicanthus correction by a
Mustarde's rectangular double Z-Plasty and trans-nasal fixation using 1-0 prolene
suture in BPES. MATERIALS AND METHODS: This was prospective, interventional study
of 16 patients over a period of three years. In this study, all patients had BPES
with prominent epicanthus and telecanthus. Mustarde's double Z-plasty and trans
nasal fixation with 1-0 prolene suture was performed in the first of a two-stage
operation. If ectropion was present, the lateral ectropion was corrected by a
base-out flap transfer from the upper eyelid to the lower eyelid. After three
months, a 2nd stage was undertaken, involving a lateral canthoplasty for
horizontal widening of a short palpebral fissure and a tarso frontalis sling with
silicone rod for correction of moderate to severe ptosis. Patients were followed
up for six months to one year with postoperative ophthalmologic examinations and
photographs. RESULTS: Out of 16 patients, 10 were females and six were males. All
the patients had bilateral involvement. In this study preoperative Inner
Intercanthal Distance (IICD) ranged from 38 mm to 42 mm and the mean IICD was
41.2+/-0.57 mm. Postoperative IICD ranged from 31 mm to 34 mm. Horizontal
Palpebral Fissure Length (HPFL) ranged from 20 mm to 23 mm and the mean value of
HPFL was 21.50 mm preoperatively. Postoperative HPFL ranged from 26 mm to 29 mm
and had a mean value of 28.50 mm, which was much improved after a combined
correction of telecanthus and lateral canthoplasty. The mean preoperative IICD
and HPFL ratio was 1.77 and was reduced to a postoperative value of 1.2. The
Marginal Reflex Distance1 (MRD-1) test value improved from +1.25 mm to +3.50 mm
postoperatively after placement of a tarsofrontalis sling with silicone rod using
the Fox's Pentagon technique. In this study, two eyes had minimal unequal
correction but were cosmetically and functionally acceptable. Correction of IICD
is possible up to 6 mm. No major complication e.g., CSF rhinorrhea was noted in
this series and preoperative prominent epicanthal folds were abolished.
CONCLUSION: Here we propose a two-staged procedure involving a combined
Mustarde's double Z-plasty with transnasal fixation using a 1-0 prolene suture
with a flap transfer from the upper lid to the lower lid in the first stage and a
lateral canthoplasty with a tarsofrontalis sling and silicone rod in the second
stage. This technique is effective to correct epicanthus, telecanthus, ptosis and
lateral ectropion in BPES with good cosmetic and functional outcome.
PMID- 28511422
TI - Posterior Chamber Scleral Fixation of Intraocular Lenses in Post-Vitrectomised
Aphakic Eyes.
AB - INTRODUCTION: The best method of aphakia correction is in the bag implantation of
Posterior Chamber Intraocular Lens (PCIOL). When this ideal procedure is not
possible due to lack of integrity of posterior capsule or zonules, the other
alternatives are broadly categorized into two: extraocular and intraocular.
Whereas, the former includes contact lenses and aphakic glasses, the latter ones
are further divided into anterior and posterior chamber methods. Anterior Chamber
Intraocular Lenses (ACIOL) can be with or without iris claw. At the posterior
chamber, fixation of the lenses can be with glue or sutures. When there is
combined Pars Plana Vitrectomy (PPV) and lensectomy or if the indication of PPV
is dropped nucleus or intraocular lens, a modality of aphakia correction should
be devised. Posterior Chamber Scleral Fixation of Intraocular Lenses (PCSFIOL)
with sutures is a preferred method because of its low complication profile.
However, data on correction of aphakia after combined PPV and lensectomy is
limited. To fill in this gap in knowledge, we evaluated the secondary PCSFIOL in
aphakic eyes after previous PPV and lensectomy. AIM: To assess the outcome and
complication profile of a large series of patients who underwent secondary
PCSFIOL implantation with sutures after combined PPV and lensectomy. MATERIALS
AND METHODS: Records of all patients who had undergone secondary PCSFIOL
implantation with sutures after combined PPV and lensectomy from 2010 to 2014
were reviewed retrospectively for visual outcomes and complications. Patients'
demographic data, indication for PPV, best corrected preoperative and
postoperative visual acuities, complications of surgery, and indications of
PCSFIOL and length of follow up were collected and analyzed. RESULTS: A total of
148 eyes of 148 patients (127 males and 21 females) were identified. Mean age at
surgery was 32.5+/-8 years (range 2.5-73 years) with a mean follow up 23+/-14
months (range 3-114 months). A total of 95.27%, 2.70% and 2.02% of patients had
improvement, maintenance and worsening of their final postoperative visual
acuities respectively. A total of 32 (21.62%) of 148 eyes had postoperative
complications from PCSFIOL with Epiretinal Membrane (ERM) formation being the
most common. They all required one form of management or the other. Suture
breakage leading to PCSFIOL subluxation or dislocation occurred in four eyes
(2.70%). CONCLUSION: PCSFIOL with sutures is a preferred method in the management
of post-vitrectomised aphakic eyes when the capsular or zonular support is not
adequate for in the bag implantation of posterior chamber intraocular lenses.
PMID- 28511423
TI - Bardet Biedl Syndrome - A Report of Two Cases with Otolaryngologic Symptoms.
AB - Bardet-Biedl Syndrome (BBS) is a rare autosomal recessive disorder characterized
primarily by rod-cone dystrophy, postaxial polydactyly, central obesity, mental
retardation, hypogonadism, and renal dysfunction. We present two cases of this
syndrome, both female, who presented with complaints of nyctalopia and mental
retardation, and additionally one of them had sensorineural hearing loss while
the other had serous otitis media. Hearing loss being a rare presentation is
worth reporting. Both the patients were given a course of vitamin A and the
parents were counseled regarding the prognosis and additional complications
associated with the syndrome.
PMID- 28511424
TI - Mechanism and Immediate Outcome of Significant Mitral Regurgitation Following
Balloon Mitral Valvuloplasty with JOMIVA Balloon.
AB - INTRODUCTION: Balloon Mitral Valvuloplasty (BMV) with inoue balloon is the most
common technique being followed worldwide. Over the wire BMV is a modified
technique with Joseph Mitral Valvuloplasty (JOMIVA) balloon and is being followed
in certain centres. We hypothesized that, the incidence and mechanism of Mitral
Regurgitation (MR) is likely to be different from that of inoue balloon. AIM: To
assess the mechanism and immediate clinical outcome of significant MR following
BMV with JOMIVA balloon retrospectively. MATERIALS AND METHODS: We
retrospectively analyzed the outcome of 48 patients who developed moderate to
severe MR out of 249 patients who underwent BMV in our institute. We analyzed the
echocardiographic and clinical parameters of these patients. RESULTS: Nineteen
(7.6%) patients developed severe MR and 29 (11.2%) patients developed moderate
MR. Commisural separation resulting in MR was the most common cause which was
contributing to 73.6 % and 85.7% of patients with moderate and severe MR
respectively. Leaflet tear was the second most common cause which contributed to
15.7% and 14.2% of patients with severe and moderate MR respectively. Chordal
rupture contributed to 10.5% of patients with severe MR. Six (31.6%) patients
with severe MR developed worsening breathlessness among them one had to be
referred for mitral valve replacement during index hospitalization and the rest
could be managed medically. Patients with moderate MR remained asymptomatic and
stable. CONCLUSION: Severe MR following JOMIVA BMV results most commonly due to
wide separation of commisures. JOMIVA balloon is less likely to cause damage to
subvalvular structures than inoue balloon. Most patients who develop severe MR
will not require emergency mitral valve replacement. Moderate MR is well
tolerated clinically.
PMID- 28511425
TI - Early Experience of Sofosbuvir based Combination Therapy in "Real-Life" Cohort
with Chronic Hepatitis-C Infection.
AB - INTRODUCTION: There is scarcity of data in literature regarding the treatment
response with Sofosbuvir (SOF) based therapy in Indian patients with chronic
Hepatitis-C Virus (HCV) infection. AIM: This study was designed to observe
initial treatment response to SOF based therapy in a "real-life" cohort of Indian
patients with HCV infection. MATERIALS AND METHODS: This is a prospective,
observational and single center study. A total of 107 patients who were diagnosed
with chronic HCV infection and received SOF based treatment between March 2015
and December 2015 were included. The patients were treated with either triple
drug regimen [SOF, Ribavirin (RBV) and Pegylated Interferon-alpha (Peg IFN
alpha)] or dual drug regimen (SOF and RBV) for either 12 or 24 weeks. The
virological responses were obtained at baseline and thereafter weekly (up to four
weeks) till viral load became undetected during treatment. RESULTS: A total of
107 patients who received SOF based therapy for chronic HCV infection were
included in the study. Mean age of the patients was 48.7+/-10.7 years. Among
included patients, 24 (22.4%) patients were treatment-experienced. Majority of
the patients (n=69; 64.5%) were infected with HCV genotype-3. Except one patient,
all the included patients achieved virological response up to week-4 of the
treatment. There was statistically insignificant association between virological
response (up to four week of the treatment) and severity of the disease
(cirrhosis and non-cirrhosis) or treatment status (treatment-naive and treatment
experienced), or HCV genotype (genotype-1 and 3). CONCLUSION: The results of this
observational study demonstrated rapid initial virological response of SOF based
therapy in "real-life" cohort of Indian patients with chronic HCV infection.
However, long-term follow-up data are needed to ensure the sustained antiviral
efficacy of SOF based therapy.
PMID- 28511426
TI - Effect of Anti-Cyclic Citrullinated Peptide and HLA-DRB1 Subtypes on Clinical
Disease Activity Index in Rheumatoid Arthritis Patients.
AB - INTRODUCTION: Rheumatoid arthritis (RA) is a crippling disease with a global
prevalence of approximately 0.5%-1% in adults. Genetic, environmental and
immunologic factors contribute importantly to pathogenesis of RA. American
College of Rheumatology (ACR) assists in early diagnosis of the disease. AIM: The
aim of this study was to investigate the effects of HLA-DRB1 gene and anti-Cyclic
Citrullinated Peptide (CCP) antibody on Clinical Disease Activity Index (CDAI)
and to determine the frequency of HLA-DRB1 alleles in the patients with RA.
MATERIALS AND METHODS: In this descriptive-analytical study, 64 patients with RA
referring rheumatology clinic of Hajar Hospital, Shahr-e-Kord, Iran were enrolled
based on ACR criteria (1987) by convenience sampling. All patients were examined
to assess primary CDAI and referred to laboratory for serologic tests [Rheumatoid
Factor (RF) and anti-CCP]. After the patients' DNA was extracted, HLA-DRB1 was
determined per single specific primer-polymerase chain reaction by inno-train
kits. The patients were re-examined six months later. RESULTS: The most prevalent
type of HLA-DRB1 in the studied patients was 04. In patients with HLA-DRB1 (04),
HLA-DRB1 (01), and HLA-DRB1 (15), CDAI decreased pronouncedly after six months,
but in other patients it did not (p<0.05). Of the patients, 81.3% had high titers
of anti-CCP, but no association between anti-CCP and CDAI was found. CONCLUSION:
RA could be a multifactorial disease. The patients with HLA-DRB1 (04), HLA-DRB1
(01) and HLA-DRB1 (15) showed a good response to routine treatments. The patients
with HLA-DRB1 (04) are likely to have no decrease in secondary CDAI. High titers
of anti-CCP in patients may indicate the severity of RA in the studied region and
perhaps environmental, genetic and unknown or idiopathic factors are
aetiologically crucial.
PMID- 28511427
TI - Role of Omega-3 Fatty Acids on Lipid Profile in Diabetic Dyslipidaemia: Single
Blind, Randomised Clinical Trial.
AB - INTRODUCTION: Diabetic dyslipidaemia is characterised by hypertriglyceridaemia,
low High Density Lipoprotein (HDL), postprandial lipimea, small and dense LDL
particles is considered to be a major predisposing factor for various
macrovascular complications. Omega-3 fatty acids are fish oil derivative
introduced in the market for dyslipidaemia associated with increased triglyceride
level. AIM: To study the effect of omega-3 fatty acids on lipid profile in Type
II diabetes patients. MATERIALS AND METHODS: This study was prospective, single
blind, randomized comparative trial. Hundred patients were randomized into three
groups. Group I received metformin 500 mg twice daily and placebo, Group II
received metformin 500 mg twice daily and omega-3 fatty acids (1 gram) once daily
and the Group III received metformin 500 mg twice daily and omega-3 fatty acids
(1 gram) twice daily. ANOVA test was applied for analysis. RESULTS: Group II was
effective in reducing the triglyceride level from 144.59+/-14.18 mg/dl to 101+/
13.31 mg/dl which was significant as compared to Group I from 147.67+/-18.57
mg/dl to 145.8+/-19.86 mg/dl respectively. Group III containing 1 g of omega-3
fatty acids twice daily showed decrease from 144.83+/-22.17 mg/dl to 86+/-17.46
mg/dl and was more effective in reducing triglyceride levels than Group II
containing 1 gram of omega-3 fatty acids once daily. CONCLUSION: Omega-3 fatty
acids can be given in conjunction with metformin to reduce triglyceride levels in
diabetic dyslipidaemia without any adverse drug reactions or any drug
interaction. Omega-3 fatty acids were effective in reducing the triglyceride
level significantly as compared to placebo. Two grams of omega-3 fatty acids were
more effective than 1 gram of omega-3 fatty acids in reducing triglyceride
levels.
PMID- 28511428
TI - Incidence of Metabolic Syndrome in Patients Admitted to Medical Wards with ST
Elevation Myocardial Infarction.
AB - INTRODUCTION: Metabolic Syndrome (MS) consists of a cluster of metabolic
abnormalities that confer exaggerated risk of cardiovascular disease. MS is a
novel risk factor for Coronary Artery Disease (CAD) and is a rising disease
entity in Asia. Incidence of ST Elevation Myocardial Infarction (STEMI) is high
in patients with MS. There is limited data on prevalence of MS in patients with
Acute Myocardial Infarction (AMI). AIM: To determine frequency of MS in patients
admitted with STEMI. MATERIALS AND METHODS: Hundred Consecutive patients between
25 to 75 years who were admitted with STEMI at Govt medical college Thrissur were
included in this prospective study. Subjects were assessed for five-component
conditions of metabolic syndrome. Criteria to identify MS were based on a
"Consensus statement for diagnosis of metabolic syndrome for Asian Indians".
Presence of three or more of following suggest MS, Waist Circumference (WC)>90 cm
in men and 80 cm in women, Blood pressure >130/85 mm Hg, Fasting Plasma Glucose
(FPG) >100 mg%, serum triglycerides >150 mg/dl, High Density Lipoprotein (HDL)<40
mg/dl in male and<50 mg/dl in female. Statistical analysis was performed using
Epi-Info software. Data expressed as numbers and percents were compared by Chi
square test. RESULTS: Study enrolled 100 patients (males 80, females 20) with a
mean age of 58. Frequency of MS in patients with STEMI was 40% (36% of males and
55% of females). Prevalence of components in the MS group was WC >80/90 -31(71%),
BP>130/85- 23(58%), FPG >100 - 37(93%), HDL <40 (male)/ 50 (female) - 18(45%), TG
>150 -15(37.5%). CONCLUSION: The present study concluded that there is a
remarkably high occurrence of metabolic syndrome and central obesity in patients
with ST elevation Myocardial Infarction (MI) in our local population especially
in females. Considering this fact the role of specific and targeted intervention
for clinical detection and management of MS including lifestyle modifications
needs to be addressed.
PMID- 28511429
TI - An Assessment of Osteoporotic Conditions among Users and Non-Users of Warfarin: A
Case-Control Study.
AB - INTRODUCTION: Warfarin is an oral anticoagulant which is associated with a
decrease in Bone Mass Density (BMD). AIM: The study aimed to explore the
prevalence of osteoporosis conditions in Malaysians with chronic warfarin
patients using calcaneal quarter of Quantitative Ultrasound (QUS) machine and to
investigate whether long-term sodium warfarin therapy that antagonizes vitamin K
is affecting the increasing rate of osteoporosis in Penang and to find the risk
factors of getting osteoporosis among warfarin users and its non users. MATERIALS
AND METHODS: A case-control study was conducted among 130 patients using
warfarin, attending the outpatient clinic at Hospital Pulau Pinang. A convenience
sampling method was used to recruit the required sample. Another 140 subjects
were selected from the community as a control group (non-users of warfarin).
RESULTS: This study showed that more than three-quarter patients (82%) were at
high risk of abnormal BMD. The warfarin users were two times more likely to have
a higher osteoporosis risk compared to control group. Moreover, BMD has a
negative correlation with age, but has a positive correlation with Body Mass
Index (BMI). Patients showed a negative correlation with a higher dose of
warfarin intake. CONCLUSION: This study concluded that osteopenia and
osteoporosis are serious problems between users and non-users warfarin in Penang.
Therefore, it should be taken into consideration in the Malaysian Health
Ministry's agenda.
PMID- 28511430
TI - Study on the Relation between Colorectal Cancer and Gall Bladder Disease.
AB - INTRODUCTION: Colorectal cancer is cancer of the large intestine, the lower part
of digestive system which includes the sigmoid colon and rectum. AIM: To study
the relation of incidence of colorectal cancer with previous gall bladder disease
or post-cholecystectomy status, a relation between gall bladder disease and
smoking in particular and the most common region of colon involved in colorectal
cancer in gall bladder disease and non-gall bladder disease patients. MATERIALS
AND METHODS: A total of 256 patients with symptoms of rectal bleeding, change in
bowel habit, unexplained tiredness, weight loss, pelvic pain, jaundice and
abdominal distension were screened by using colonoscopy among whom 30 patients
were diagnosed with colorectal cancer. Detailed history was taken with the help
of a modified questionnaire and the patients were assessed, examined and the list
of investigations such as faecal occult blood test, ultrasound of abdomen and
pelvis, colonoscopy, sigmoidoscopy, barium enema, Computed Tomography (CT),
Magnetic Resonance Imaging (MRI) of the abdomen and pelvis, tumour markers like
Carcinoembryonic Antigen (CEA) and biopsy were collected. Patient pool was
categorized into Gall Bladder Disease (GBD) and Non Gall Bladder Disease (NGBD).
Proportions test and Fisher's-Exact test were used to calculate the p-values.
RESULTS: Ten patients had previous gall bladder disease (33%) which was
significant with a p-value of 0.016 by proportions test. Two patients underwent
cholecystectomy, two patients underwent Endoscopic Retrograde Cholangio
Pancreatography (ERCP) and the remaining six patients did not take any treatment
for their gall bladder disease. Five patients with previous gall bladder disease
were found to be smokers with a p-value of 0.091. The average age was 47.2 years
in males and 42.2 years in females. Males constituted 66.6% (20 males) of the
diseased population whereas, females constituted 33.4% (10 females). Rectal
bleeding and altered bowel habits were the commonest symptoms. Confirmation of
the disease was proven using CT abdomen and biopsy. Right sided colorectal cancer
was common in GBD patients. Left sided colon cancer was common in NGBD patients.
CONCLUSION: This study established a statistically significant risk of colorectal
cancer following cholelithiasis though no risk was apparent following
cholecystectomy.
PMID- 28511431
TI - The Relationship between Serum Level of Vitamin D3 and the Severity of New Onset
Rheumatoid Arthritis Activity.
AB - INTRODUCTION: Rheumatoid Arthritis (RA) is a systemic inflammatory disease which
typically involves wrists, ankles, and finally every joint. Some of studies have
reported a reverse relationship between the level of vitamin D and RA severity.
AIM: The present study was carried out in order to check the potential
relationship between the level of vitamin D and RA severity. MATERIALS AND
METHODS: Ninety-three patients with RA with onset in recent three months (new
onset RA), and 31 patients without RA were chosen as the control group. The
patients all aged under 75 years and were diagnosed by a rheumatologist. The
serum level of vitamin D was measured through blood test by chemiluminescence
method by taking a blood sample of 5 cc. The relationship between the average
level of vitamin D and disease severity was analyzed based on scoring scale of
DAS28 in different groups with RA. The significant level of the above mentioned
tests was set at p<0.05. Data analysis was carried out using SPSS 20.0. RESULTS:
The results of the present study indicated that there was no significant
relationship between the two groups in terms of the serum level of vitamin D.
Since the subgroups of the patients are not homogenous in terms of age and based
on disease severity, ANOVA and chi-square were used to modify this heterogeneity
and compare vitamin D levels in patients based on disease severity. The results
indicated that there was a significant difference between the three groups of
patients in terms of disease severity, such that disease severity rose with a
decrease in the serum level of vitamin D, (p-value <0.001). CONCLUSION: There was
a significant reverse relationship between the serum level of vitamin D and RA
severity based on Das Score 28. Therefore, it is recommended that if there is a
lack of or insufficient amounts of this vitamin in the body, vitamin D supply
needs to be optimized along with other standard medications in order to reduce
the RA severity.
PMID- 28511432
TI - Mutations in Hepatitis-B X-Gene Region: Chronic Hepatitis-B versus Cirrhosis.
AB - INTRODUCTION: Specific mutations in Hepatitis-B Virus (HBV) genome would proceed
the development of chronic hepatitis B to more serious consequences like
cirrhosis and end-stage liver disease. AIM: This study was designed to detect
deletion and insertion mutational patterns in the X-gene region in a population
of chronic HBV and related cirrhosis patients. MATERIALS AND METHODS: Sixty eight
chronic HBV patients and 34 HBV-related cirrhotics were recruited from the
eligible cases (N=50) referred to the academic hospitals of Gorgan city,
Northeast of Iran, between Jan 2011 to Dec 2013. The HBx region was amplified by
semi-nested PCR using serum samples and analyzed by sequencing. RESULTS: Our
findings showed deletions and insertions in the C-terminal of HBx of the
cirrhotic group and 8 bp found in two chronic HBV cases (2.9%). We detected 15
types of deletions in cirrhotic cases such as 1762-1768, 1763-1770, 1769-1773 and
T1771/A1775. CONCLUSION: We found that the frequencies of deletion and insertion
mutations in C-terminal of X-gene were more seen in cirrhotic patients comparing
to chronic HBV cases in our area of study.
PMID- 28511433
TI - Clinico-Radiologic and Spirometric Profile of an Indian Population with Post
Tuberculous Obstructive Airway Disease.
AB - INTRODUCTION: Tuberculosis is a public health problem in developing countries and
in spite of receiving adequate anti-tuberculous therapy, patients often continues
to have several post-tuberculous sequelae, especially airflow limitation. AIM: To
evaluate pulmonary function by spirometry among post-tuberculosis cases with
airway obstruction and their relationship with smoking. MATERIALS AND METHODS:
All patients who presented to the pulmonary medicine Outpatient Department (OPD)
with symptoms of obstructive airway disease and had completed adequate anti
tuberculous therapy for pulmonary tuberculosis were taken up for study. They were
initially evaluated with sputum smear for Acid Fast Bacilli (AFB) and chest X
ray. Patients without evidence of active tuberculosis underwent spirometry and
those having post-bronchodilator Forced Expiratory Volume in first second (FEV1)/
Forced Vital Capacity (FVC) FEV1/FVC<0.7 were taken up for final analysis.
Spirometric parameters were compared between smokers and non-smokers. RESULTS:
Out of 138 finally selected cases, 84.06% were male and 71.01% were within age
range of 40-69 years. Significant positive association was found between extent
of radiologic lesion and severity of airflow obstruction. Purely obstructive
pattern was found in 27.54% cases and 72.46% showed mixed pattern. Patients with
mixed ventilatory abnormality had worse pulmonary function and poorer
bronchodilator reversibility than patients with pure obstruction. Comparison of
post-bronchodilator FEV1, FVC, Peak Expiratory Flow (PEF) and Forced Expiratory
Flow (FEF) 25-75 between smokers and non-smokers did not show statistically
significant difference. CONCLUSION: Majority of patients with post-tuberculous
obstructive airway disease have associated restrictive component. But smoking did
not cause significant alteration in pulmonary function among such patients.
PMID- 28511434
TI - Anti-C1q Antibody is Associated with Renal and Cutaneous Manifestations in Asian
Indian Patients with Systemic Lupus Erythematosus.
AB - INTRODUCTION: C1q play an important role in clearance of immune complexes and
apoptotic cell debris. Impaired clearance leads to exposure of C1 native antigen
and development of anti-C1q antibody formation. Anti-C1q antibody is well studied
in Systemic Lupus Erythematosus (SLE). Significance of anti-C1q Ab in Indian SLE
patients and their clinical manifestations is not clear. AIM: The aim of this
study was to investigate associations between anti-C1q antibody and clinical as
well as serological markers of SLE. MATERIALS AND METHODS: Retrospective study of
SLE patients fulfilling either American College of Rheumatology (ACR) 1990 or
Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification
criteria were recruited from inpatients and outpatients services of the Clinical
immunology and Rheumatology Department, Christian Medical College at Vellore,
India between March 2013 and January 2015. Anti-C1q antibody was assayed by ELISA
(Demeditec Diagnostics GmbH, Germany). Logistic regression analysis was performed
to find the association of anti-C1q antibodies with serological and clinical
parameters in SLE including Lupus Nephritis (LN). RESULTS: Sixty nine patients
(54.76%) out of 126 SLE patients had LN. Anti-C1q levels were higher in patients
with LN as compared to those without (p<0.05). Anti-C1q antibody was also
significantly associated with positive C1q immunofluorescence staining in renal
biopsy specimens (p<0.05). Overall, renal Systemic Lupus Erythematosus Disease
Activity Index (SLEDAI) {OR 1.35 (1.08-1.69)}, low C4 {OR 3.11 (1.04-9.26)} and
mucocutaneous manifestation {OR 4.72 (1.38-16.05)} were independently associated
with anti-C1q levels in serum. CONCLUSION: Renal SLEDAI, low C4 and mucocutaneous
manifestations were independently associated with raised anti C1q antibody in SLE
patients.
PMID- 28511435
TI - Agreement and Correlation between Arterial and Central Venous Blood Gas Following
Coronary Artery Bypass Graft Surgery.
AB - INTRODUCTION: Arterial blood sampling, used to assess patients in acute
conditions, may result in complications such as thrombosis and embolism. However,
it can be replaced by venous blood sampling, but there is a dearth of information
on this. AIM: To assess the correlation and agreement between the arterial and
central venous blood gases analyses in patients undergoing elective Coronary
Artery Bypass Graft (CABG) surgery. MATERIALS AND METHODS: In this cross
sectional study, 100 ICU patients undergoing elective CABG surgery were
recruited. 2 mm arterial and a 2 mm venous blood samples were obtained from each
patient's arterial and central venous lines, respectively. To predict Arterial
Blood Gas (ABG) values based on central Venous Blood Gas (VBG) values, the linear
regression analysis was used and for evaluating their agreement Bland-Altman
method was used. RESULTS: In total of 200 samples were obtained. The mean and
Standard Deviation (SD) of age was 58.9+/-9.1 years and 51% of the participants
were female. There was a strong correlation between ABG and central VBG values
regarding pH, partial Pressure of Carbon Dioxide (PCO2), Bicarbonate (HCO3) and
Base Excess (BE) (r= 0.73, r=0.74, r=0.67 and r=0.71, respectively; p<0.001);
however, the correlation between the arterial and venous Partial Pressure of
Oxygen (PO2) and Oxygen Saturation (SO2) was moderate (r=0.29, p=0.005 and
r=0.27, p=0.006, respectively). The Bland-Altman analysis showed an excellent
agreement between all the variables (p<0.001). CONCLUSION: Central VBG analysis
cannot replace ABG analysis in measuring exact PO2 status, necessitating arterial
sampling in some matters, but with respect to the accuracy of pulse oximetry
measurements in determining the exact PO2 status, for the rest of the indices a
central VBG rather than an ABG can be utilised for determining patient's acid
base status. Particularly in patients who are hospitalised for a long time and
have a central venous catheter in place like patients who have undergone CABG,
thus reducing the risk and need for invasive arterial sampling.
PMID- 28511436
TI - Glycaemic and Insulin Response to Equi-Quantity of Selected Common Indian Staples
in Individuals with Type 2 Diabetes Mellitus.
AB - INTRODUCTION: Diet therapy is one of the corner stone's in the management of
diabetes. Keeping the blood sugar level as close to normal is the main focus of
dietary management of diabetes. A typical Indian meal is largely composed of
Carbohydrates (CHO). Consumption of staple cereals, forms the major source of CHO
in the Indian diet. However, CHO metabolism is seen to be completely deranged in
a person with type 2 diabetes. It is necessary to select the cereal which has
lower postprandial glycaemic impact for subjects with compromised metabolic
status. Preference between two main staple cereals rice and wheat as staple food,
especially for diabetic group, will depend on the equi-quantity based
postprandial glycaemic impact of these cereals. AIM: To identify the cereals,
better suited for individuals with diabetes (based on postprandial glycaemic and
insulinemic impact of rice and whole wheat Indian flat bread i.e., chapatti).
MATERIALS AND METHODS: After an overnight fast and upto 2 hours for every half an
hour, finger tip blood samples for fasting and postprandial blood sugar was
assessed. Venous blood for estimation of insulin levels were also collected from
enrolled diabetic individuals and paired normal subjects. About 50 gm of test
food like boiled rice, whole wheat chapatti and white bread as standard food were
given on different occasions. Glucose and insulin levels were measured using
glucometer and ECLIA method. RESULTS: Contrary to the popular belief, it was seen
that rice exerted a lower peak and lower postprandial glycaemic and insulinemic
response in both the study groups. Factors such as co-nutrient, moisture and
fiber content all exert an impact on the postprandial glucose and insulin levels.
With this the grain structure, particle size and amylose: amylopectin ratio are
also important determinants. CONCLUSION: When foods are considered as a whole and
not a single nutrient, rice proves to be a better product for effective
management of blood sugars in individuals with type 2 diabetes mellitus.
PMID- 28511437
TI - Children's Physical Activity Awareness among Mothers in a Saudi Arabian Health
Center.
AB - INTRODUCTION: Physical inactivity is a major contributor to the increasing levels
of obesity and other serious medical conditions among children and adolescents
worldwide. A major factor in this increase is lack of awareness of mothers'
regarding the Physical Activity (PA) of their children. AIM: The current study
aimed to identify the degree of knowledge and awareness of Saudi mothers'
regarding their children's physical activities, which will be useful for
improving physical education, health programs, and eventually children's health
care. MATERIALS AND METHODS: A total of 342 mothers attending a vaccination
clinic, well-baby, or women's health clinic participated in the study, in which
questionnaire was used to assess the awareness regarding PA. RESULTS: The
majority of mothers agreed that they have a crucial role in motivating their
children to engage in PA, but was not aware of current recommendations.
CONCLUSION: Awareness of Saudi mothers' regarding their children's PA was
exceedingly low. Creating awareness of children's PA is essential.
PMID- 28511438
TI - Assessing the Safety and Clinical Impact of Thoracoscopic Lung Biopsy in Patients
with Interstitial Lung Disease.
AB - INTRODUCTION: The clinical relevance of surgical lung biopsy in Interstitial Lung
Disease (ILD) is supported in the literature. Yet most reports reflect
institutional or personal bias. AIM: To evaluate the validity of radiologic
diagnosis and clinical impact of lung biopsy to help clarify which patient
benefit most from biopsy. MATERIALS AND METHODS: We performed a retrospective
analysis of a prospectively managed database. All patients who had a surgical
lung biopsy for ILD within a period of four year (2009 to 2013) were included.
Data included patient demographics, peri-operative variables and outcomes.
Preoperative Computed Tomography (CT) imaging was reviewed by a thoracic
radiologist blinded to the original report and pathologic information. RESULTS: A
total of 47 patients were included. Lung tissue was obtained via a thoracoscopic
approach in all but two that had mini-thoracotomy. Mean operating time was 51.1
minutes (18-123), median hospital stay was two days (1-18). Most (87.2%) of the
patients were discharged within 72 hours. Thirty day mortality for elective
surgery was 4.5% (2/44). Post-operative complications occurred in about one third
of the patients. Complications in elective procedures included pneumothorax
(10.4%), re-intubation (5.4%) and prolonged intubation (2.7%). Full concordance
of radiographic diagnosis with the final diagnosis was significantly higher when
reviewed by a cardiothoracic radiologist (60.5% vs. 21.3%). The preoperative
clinical diagnosis was fully concordant with the final diagnosis in only 28.2% of
cases. In 13.0% of patients the preoperative diagnosis was incorrect. Malignancy
was the final diagnosis in two (4.3%) patients. In 51.1% of the patients, results
of the biopsy did alter therapy. CONCLUSION: Diagnosis of specific ILD by a
cardiothoracic radiologist is more specific and accurate and will probably lead
to more appropriate therapy. Elective thoracoscopic surgical lung biopsy is a
safe procedure, leads to a more accurate diagnosis of ILD and impacts therapy.
PMID- 28511440
TI - Portal Venous Thrombosis: Eosinophilic Vasculitis.
AB - Portal Vein Thrombosis (PVT) is caused by various thrombophilic states. PVT
secondary to underlying vasculitis especially Churg-Strauss disease is among the
rarest presentation. Here, we report a case of peripheral eosinophilia,
eosinophilic ascitis and venous thrombosis involving portal vein and superior
mesenteric vein diagnosed as Churg-Strauss Syndrome (CSS). He was managed with
steroids and anticoagulants. Following initiation of steroids, eosinophilia and
eosinophilic ascitis improved.
PMID- 28511439
TI - Light Chain Myeloma induced Severe Hypertriglyceridemia.
AB - Hyperlipidemia is very common in general population and incidence has further
increased in recent years. Evaluation of patient presenting with lipid disorders
is essential to obtain a definite diagnosis to prevent complications, and apply
the most appropriate treatment. An isolated elevation in triglyceride levels may
be caused by a primary disorder of lipid metabolism like familial
hypertriglyceridemia. It may also arise secondary to a number of conditions like
diabetes mellitus, alcohol intake, hypothyroidism, drugs, infections and
nephrotic syndrome. Herein, we describe a case of secondary hypertriglyceridemia
leading to Nonalcoholic Steatohepatitis (NASH) in a young female which was
attributed to Multiple Myeloma (MM). Significant reduction in triglyceride levels
after starting anti-myeloma therapy established their relation. This is the first
case of light chain myeloma causing severe secondary hypertriglyceridemia.
PMID- 28511441
TI - Catheter-Assisted Balloon-Supported Retrieval of a Broken Semi-Compliant Balloon
from a Coronary Artery.
AB - Incidents of broken balloon in a coronary vasculature during percutaneous
coronary angioplasty are very rare. Such events in cath-lab may create panic and
can be life threatening for patients. Hence, immediate retrieval of broken
balloon becomes vital. Here, we report an unusual complication of broken balloon
in the mid portion of the left anterior descending coronary artery, which had a
calcified and totally occluded in-stent restenotic lesion. The broken balloon was
retrieved successfully with no eventual complication using a simple catheter
assisted balloon-supported retrieval technique. The present case highlights the
need for interventional cardiologist to be acquainted with different retrieval
techniques.
PMID- 28511442
TI - Cannon Ball Lung Metastases from a Previously Unreported Primary.
PMID- 28511443
TI - Patent Vitellointestinal Duct with Patent Urachus Presenting as Umbilical
Discharge.
AB - Patent urachus with patent vitellointestinal duct is a rare combination to
present in the same patient. We present a rare case of one year old male child
with such a condition presenting with complaint of discharge from umblicus along
with severe anaemia and an umblical granuloma. On exploratory laparotomy, patent
tracts joining umblicus to ileum and umblicus to apex of urinary bladder were
found. Both the tracts were excised and appropriate closure was done. Patient had
been under follow up and is doing well.
PMID- 28511444
TI - Pseudoangiomatous Stromal Hyperplasia: A Rare Cause of Breast Lump in a
Premenopausal Female.
AB - Pseudoangiomatous Stromal Hyperplasia (PASH) of the breast is a rare benign
proliferating breast condition. We report a case of a 26-year-old female who was
being worked up for infertility and was incidentally noted to have a well defined
lump in the left breast. Fine Needle Aspiration Cytology (FNAC) and core needle
biopsy of the lump were suggestive of benign breast disease. Patient underwent
excision of the lump. Histopathology report of which was suggestive of PASH of
the breast.
PMID- 28511445
TI - Neoumbilicoplasty in a Laparoscopic Port Site: Description of a New Technique and
Review of Literature.
AB - The umbilicus contributes significantly to the cosmetic appearance of the abdomen
especially in women. Loss of umbilicus may result not only in cosmetic
disfigurement but also in significant psychological effects. Omphalectomy may
accompany certain surgical procedures like ventral hernia repairs and
abdominoplasty. For such patients, many techniques have been described by various
authors in literature for creation of a neoumbilicus for good cosmetic
appearance. In this report, we describe how a laparoscopic port site was utilized
to create a neoumbilicus in a patient who required omphalectomy as a part of
large umbilical hernia repair. Satisfactory postoperative result promted us to
report this novel technique of neoumbilicus creation. This can be utilized in
patients who have been previously subjected to laparoscopic procedures. This is
the first case description in literature where a laparoscopic port scar was
utilized for neoumbilicoplasty.
PMID- 28511446
TI - Thromboangitis Obliterans involving Bilateral Upper limb Extremities - A Rare
Case Report from Malaysia.
AB - Thromboangitis Obliterans (TAO) or Buerger's disease is a non-atherosclerotic,
occlusive, progressive and highly inflammatory disorder of distal arteries seen
predominantly affecting the lower limb in smokers. TAO presenting itself in upper
limb or bilaterally involving the upper limb is a very rare entity. We report on
a rare case of TAO in a 46-year-old gentleman who presented with bilateral upper
extremity digital gangrene with 18 pack-years of smoking. Brachial and radial
pulses were palpable bilaterally and were of good volume but right ulnar pulse
was faintly felt, while on the left side it was not appreciated due to malunion.
Further Computed Tomography (CT)- angiography showed occlusion of distal right
ulnar artery, stenosis of distal left ulnar artery with bilateral poor
opacification of palmar and digital arteries. This case reports on the unusual
and rare presentation of TAO in upper extremity involving both limbs. The case is
reported for the first time from Malaysia.
PMID- 28511448
TI - Rectus Sheath Haematoma Secondary to Enoxaparin Injection- A Rare Case Report.
AB - Rectus sheath haematoma is a well-documented condition with an elusive diagnosis.
It is an uncommon complication of anti-coagulation therapy, which can have a
mortality of upto 25%. The patient discussed here is a 40-year-old female who was
on Inj. Enoxaparin, who developed severe abdominal pain and hypovolemia after
three days of treatment. Ultrasonography and CT scan showed a large rectus sheath
haematoma on the right side, which was crossing the midline towards the left
side. Inj. Enoxaparin was stopped and the patient was posted for surgery. In
surgery, all clots were evacuated and inferior epigastric vessels were ligated.
Patient recovered well following surgery. Here, this report presents forward a
case of rectus sheath haematoma secondary to enoxaparin injection, its
presentation and its surgical management.
PMID- 28511447
TI - Delayed Presentation of Isolated Jejunal Perforation Following Accidental Trauma.
AB - Blunt abdominal trauma can injure any abdominal organs which had significant
morbidity and mortality in paediatric age group. It can lead to duodenal, jejunal
or rather any bowel perforation. Isolated jejunal perforation still remains rare
entity with less documented reports in specifically paediatric age group. We
hereby present a case of three-year-old female child with isolated jejunal
perforation, post history of fall from height. Early exploration and prompt
surgical intervention led to successful outcome in this patient.
PMID- 28511449
TI - Management of Accidental and Iatrogenic Foreign Body Injuries to Heart- Case
Series.
AB - Accidental and iatrogenic foreign body injuries to heart require immediate
attention and its timely management is cornerstone to the life of an individual.
We describe in detail five cases of Accidental and iatrogenic foreign body
injuries to heart encountered between January 2013 and July 2016. Our series
included the following: needle stick injury to the right atrium (1 case) retained
catheter fragments in the distal main pulmonary artery (1 case), right ventricle
injury during catheterisation study (1 case), right ventricle injury during
permanent pacemaker lead placement (1 case), device migration in atrial septal
defect closure (1 case). Foreign bodies were removed from the cardiac cavities
when the patient presented with features of infection (1 case), cardiac tamponade
(2 case), anxiety (1 case), and haemodynamic instability (1 case). The management
of accidental and iatrogenic foreign body injuries to heart requires immediate
attention. Foreign bodies in the heart should be removed irrespective of their
location and symptomatology. Asymptomatic foreign bodies diagnosed immediately
after the injury with associated risk factors should be removed; asymptomatic
foreign bodies without associated risks factors or diagnosed accidentally after
the injury also need surgical intervention to allay fears of anxiety in patient
and their relatives, to prevent any late complications and also for medico-legal
purpose.
PMID- 28511450
TI - Emergency Peripartum Hysterectomy: Indications and Outcome in a Tertiary Care
Setting.
AB - INTRODUCTION: Emergency Peripartum Hysterectomy (EPH) is an important lifesaving
procedure, mostly reserved for conditions deemed to be serious and life
threatening, and not amenable to conservative methods. In the present scenario,
the advent of newer medical and conservative surgical methods for controlling
obstetric haemorrhage has influenced the incidence, trend and the outcomes of the
procedure. AIM: To evaluate the demographic profile, indications, operative
details, maternal morbidity and mortality and neonatal outcomes of women
undergoing EPH. MATERIALS AND METHODS: A descriptive analysis of case records of
women who underwent EPH between September 2006 to July 2014, at Guru Teg Bahadur
Hospital Delhi, India was done. Data were collected from the medical records
department. RESULTS: A total of 194 cases (n) were identified among 1,00712
deliveries, an incidence of 1.92 per 1000 deliveries. Majority of the women were
unbooked i.e., they did not receive any form of antenatal care and were gravida 3
and above. The indications were atonic PPH in 89 (45.87%), rupture of unscarred
uterus in 36 (18.56%), morbidly adhered placenta in 30 (15.46%), scar rupture in
20 (10.31%) and gangrenous uterus 19 (9.79%). The mean blood loss was around
1.6+/-0.45 litres. Approximately 14% cases underwent stepwise devascularisation
prior to hysterectomy and in only 2% women, B-Lynch suture was applied. Thirteen
(6.7%) cases had bladder injury and 22 (11.34%) needed re-laparotomy for
hysterectomy. Around 76 (39%) women were shifted for ICU care. Nineteen (9.79%)
women developed Disseminated Intravascular Coagulation (DIC). The case fatality
rate was 7.2% and perinatal mortality was 30%. CONCLUSION: Atonic PPH remains the
leading cause of EPH in our analysis. Surprisingly rupture of unscarred uterus
was more common compared to scar rupture. Creating awareness among women to seek
health services in time with facilities for early referral, teaching younger
obstetricians with conservative surgical procedures like stepwise
devascularisation steps and compressive sutures should be of utmost priority.
PMID- 28511451
TI - Attitudes of Mashhad Public Hospital's Nurses and Midwives toward the Causes and
Rates of Medical Errors Reporting.
AB - INTRODUCTION: Patient's safety is one of the main objective in healthcare
services; however medical errors are a prevalent potential occurrence for the
patients in treatment systems. Medical errors lead to an increase in mortality
rate of the patients and challenges such as prolonging of the inpatient period in
the hospitals and increased cost. Controlling the medical errors is very
important, because these errors besides being costly, threaten the patient's
safety. AIM: To evaluate the attitudes of nurses and midwives toward the causes
and rates of medical errors reporting. MATERIALS AND METHODS: It was a cross
sectional observational study. The study population was 140 midwives and nurses
employed in Mashhad Public Hospitals. The data collection was done through
Goldstone 2001 revised questionnaire. SPSS 11.5 software was used for data
analysis. To analyze data, descriptive and inferential analytic statistics were
used. Standard deviation and relative frequency distribution, descriptive
statistics were used for calculation of the mean and the results were adjusted as
tables and charts. Chi-square test was used for the inferential analysis of the
data. RESULTS: Most of midwives and nurses (39.4%) were in age range of 25 to 34
years and the lowest percentage (2.2%) were in age range of 55-59 years. The
highest average of medical errors was related to employees with three-four years
of work experience, while the lowest average was related to those with one-two
years of work experience. The highest average of medical errors was during the
evening shift, while the lowest were during the night shift. Three main causes of
medical errors were considered: illegibile physician prescription orders,
similarity of names in different drugs and nurse fatigueness. CONCLUSION: The
most important causes for medical errors from the viewpoints of nurses and
midwives are illegible physician's order, drug name similarity with other drugs,
nurse's fatigueness and damaged label or packaging of the drug, respectively.
Head nurse feedback, peer feedback, fear of punishment or job loss were
considered as reasons for under reporting of medical errors. This research
demonstrates the need for greater attention to be paid to the causes of medical
errors.
PMID- 28511452
TI - The Effect of Entonox on Labour Pain Relief among Nulliparous Women: A Randomized
Controlled Trial.
AB - INTRODUCTION: Labour pain is one of the most severe pain in humans. Fear of
labour pain is the most dreadful reason for Caesarean Section (CS). Entonox (a
mixture of nitrous oxide+oxygen) is a safe inhalational analgesia during labour
pain. AIM: This study investigated the effect of entonox on pain relief and
length of labour in nulliparous women. MATERIALS AND METHODS: A clinical trial
study was conducted among 120 nulliparous women (60 in intervention and 60 in
control group) in 2015 in Atieh Hospital, Hamadan city, Iran. The women were
chosen randomly to receive either entonox in the intervention group or oxygen in
the control group. For the intervention group, entonox inhalation was introduced
at the initiation of pain at each contraction. entonox gas was administrated via
a face-mask. This enabled the women to breathe fresh gas in each inspiration. In
the control group the oxygen inhalation was given with occurrence of pain at each
contraction too. In both groups, the gas administration continued until the end
of contraction pain with the patient finally breathing room air. Pain using
Visual Analogue Scale (VAS), duration of labour and side effects were compared in
two groups. RESULTS: The mean age of women was 25.69 (SD=4.83). There were
significant differences between two groups on labour pain at the first, second,
third and fourth hours after intervention (p<0.05). Duration of labour in the
intervention group (64.80 minutes) was significantly shorter than the control
group (98.33 minutes) (p<0.05). There were no significant differences between the
two groups on women's blood pressure and neonatal Apgar score. Only dizziness was
slightly higher in the intervention group compared to the control group (p<0.05).
CONCLUSION: Entonox provides significant pain relief and it can quickly be
implemented during painful labour.
PMID- 28511453
TI - Pregnancy Outcome of Abnormal Nuchal Translucency: A Systematic Review.
AB - INTRODUCTION: Nuchal Translucency (NT) is the sonographic form of subcutaneous
gathering of liquid behind the foetal neck in the first trimester of pregnancy.
There is association of increased NT with chromosomal and non-chromosomal
abnormalities. AIM: The purpose of this systemic review was to review the
pregnancy outcome of abnormal nuchal translucency. MATERIALS AND METHODS: The
present systematic review was conducted by searching English language articles
from sources such as International Medical Sciences, Medline, Web of science,
Scopus, Google Scholar, PubMed, Index Copernicus, DOAJ, EBSCO-CINAHL. Persian
articles were searched from Iranmedex and SID sources. Related key words were
"outcome", "pregnancy", "abnormal", and "Nuchal Translucency" (NT). All,
randomized, descriptive, analytic-descriptive, case control study conducted
during 1997-2015 were included. RESULTS: Including duplicate articles, 95 related
articles were found. After reviewing article titles, 30 unrelated article and
abstracts were removed, and 65 articles were evaluated of which 30 articles were
duplicate. Finally 22 articles were selected for final analysis. Exclusion
criteria were, case studies and reports and quasi experimental designs. This
evaluation has optioned negative relationship between nuchal translucency and
pregnancy result. Rate of cardiac, chromosomal and other defects are correlated
with increased NT>=2.5mm. Cardiac disease which were associated to the increased
NT are heart murmur, systolic organic murmur, Atrial Septal Defect (ASD),
Ventricular Septal Defect (VSD), tricuspid valve insufficiency and pulmonary
valve insufficiency, Inferior Vena Cava (IVC) and Patent Ductus Arteriosus (PDA).
The most common problems that related with increased NT were allergic symptoms.
CONCLUSION: According to this systematic review, increased NT is associated with
various foetal defects. To verify the presence of malformations, birth defect
consultations with a perinatologist and additional tests are required.
PMID- 28511454
TI - The Factor Structure and Psychometric Properties of the Persian Version of the
Revised Prenatal Coping Inventory (Nu-PCI).
AB - INTRODUCTION: Familiarity with coping strategies is essential for stress
management during pregnancy. The Revised Prenatal Coping Inventory (Nu-PCI) was
developed to assess coping strategies during pregnancy. AIM: This study aimed to
assess the factor structure and psychometric properties of the Persian version of
the Nu-PCI. MATERIALS AND METHODS: After forward-backward translation, the Nu-PCI
was administered to 210 pregnant women who were enrolled in two teaching referral
clinics in the North of the Islamic Republic of Iran (Babol). The participants
completed the Persian Nu-PCI and Ways of Coping Questionnaire (WCQ), which was
used to determine the validity of the Persian Nu-PCI. To test construct validity
of the Persian Nu-PCI, a principal components factor analysis was performed.
RESULTS: Principal components analysis with varimax rotation showed a best
fitting 3-factor structure similar to the original with three coping subscales:
planning-preparation, avoidance, and spiritual-positive coping. The Persian Nu
PCI was internally consistent and within the acceptable range (alpha=0.89-0.97).
The alpha coefficients for the Nu-PCI and the subscales of planning-preparation,
avoidance, and spiritual-positive coping were high. Test-retest coefficients for
the Nu-PCI and subscales were 0.98-0.99. The Nu-PCI and its subscales correlated
with the WCQ in the entire sample and within each trimester. CONCLUSION: The
Persian version of the Nu-PCI and the subscales of planning-preparation,
avoidance, and spiritual-positive coping represent the first reliable
standardized tool for measuring coping strategies during pregnancy in the Islamic
Republic of Iran. Therefore, it can be applied as a quick and accurate
preliminary screening tool for evaluating coping strategies throughout pregnancy
in clinics and other medical and research settings.
PMID- 28511455
TI - Cervical Conization and the Risk of Preterm Birth: A Population-Based
Multicentric Trial of Turkish Cohort.
AB - INTRODUCTION: Cold Knife Conization (CKC) is one of the most effective methods
for the treatment of Cervical Intraepithelial Neoplasia (CIN). Some studies
showed a relation between preterm birth and the treatment of CIN; on the other
hand, other studies do not show such a relationship. AIM: The present study was
conducted with the aim to investigate the pregnancy outcomes of Turkish women
regarding demographic characteristics, obstetric history, removed tissue, and
residual cervical length after CKC and to determine the effect of removed
cervical tissue volume and height on preterm birth. MATERIALS AND METHODS: This
study was a population-based, multicenter trial that was conducted on singleton
pregnancies between January 2007 and December 2013. The control group comprised
of 38,892 patients who gave birth during this period. On the other hand, patients
who conceived after CKC during this period were invited to the hospital and
included in the case group (n=20). The course of pregnancy following CKC was
studied. Preterm birth rates, risk factors for preterm birth, conisation age,
cervical smear and colposcopic biopsy results and the volume and height of the
removed cervical tissue of those patients were evaluated. RESULTS: There was no
statistically significant difference in preterm birth rates between the case and
the control groups. None of our cases had any identified preterm birth risk
factor except for one case. The average height of removed cervical tissue was
12.6+/-5.4 mm and the average length of the residual cervix after birth was
28.7+/-4.3 mm. CONCLUSION: Removal of cervical tissue of 12.6+/-5.4 mm in height
and 2.35+/-2.27 cm3 in volume will not increase the risk of preterm birth of
women who do not have any other preterm birth risk factors. If there is no other
preterm birth risk factors, term birth is most probably possible after
conisation.
PMID- 28511456
TI - Acute Rubella Virus Infection among Women with Spontaneous Abortion in Mwanza
City, Tanzania.
AB - INTRODUCTION: Acute rubella virus infection in early pregnancy has been
associated with poor pregnancy outcome ranging from spontaneous abortion,
stillbirth and multiple birth defects known as Congenital Rubella Syndrome (CRS).
Despite its importance the prevalence of acute rubella virus infections is not
known among women with spontaneous abortion in most centres in developing
countries. AIM: The present study was aimed to determine the seroprevalence of
acute rubella infection among women with spontaneous abortion in Mwanza city.
MATERIALS AND METHODS: A total of 268 women with spontaneous abortion were
enrolled from four different hospitals in Mwanza city between November 2015 and
April 2016. Blood samples were collected; sera were extracted and stored at -80
degrees C until processing. Acute rubella virus infection was diagnosed by the
detection of rubella specific IgM antibodies using indirect Enzyme Linked
Immunosorbent Assay (ELISA) as per manufacturer's instructions. Data were
analysed by using STATA version 11. RESULTS: The mean age of enrolled women was
26.3+/-5.6 years. The prevalence of acute rubella virus infection was found to be
9/268 (3.7%, 95% CI: 1-5). Only women residing in urban areas (AOR: 5.65, 95% CI:
1.15-27.77, p=0.035) were found to predict acute rubella virus infection among
cases with spontaneous abortion in Mwanza city. CONCLUSION: About four out of
hundred women residing in urban areas with spontaneous abortion in Mwanza are
acutely infected with rubella virus highlighting the potential of this virus in
contributing to poor pregnancy outcome in this setting.
PMID- 28511457
TI - Leptin as a Predictive Marker in Unexplained Infertility in North Indian
Population.
AB - INTRODUCTION: According to WHO, the primary infertility in India is about 3.9%
(age-standardized to 25-49 year) and 16.8% (age-standardized to 15-49 year),
using the "age but no birth" definition. Several factors which affect fertility
include low sperm production in men, poor egg quality and blocked fallopian tubes
in women and also hormonal imbalances. Leptin plays a critical role in women's
reproduction and neuroendocrine health. It is used for treating exercise-induced
bone loss, eating disorders and infertility. AIM: To evaluate the serum leptin
levels in Indians and to ascertain the relationship between serum leptin levels,
Unexplained Infertility (UI) and related variables [height, weight, Waist Hip
Ratio (WHR), Body Mass Index (BMI)] between obese infertile, non-obese infertile
and healthy subjects. MATERIALS AND METHODS: The present case-control study was
conducted at the Department of Obstetrics and Gynaecology, King George's Medical
University (KGMU), Lucknow, India and funded by Department of Science and
Technology, New Delhi, India. The study included 229 female participants in the
age group of 18-40 years (120 cases and 109 controls) who were randomly selected.
The blood samples were collected from the Infertility Clinic, Queen Mary's
Hospital, KGMU, Lucknow, India. All the participants underwent complete physical
examination. Initially, the participants were categorized into fertile and
infertile groups, they were further divided on the basis of BMI, normal (BMI-
18.5-24.5) and overweight or obese (BMI>=25). Leptin level was measured by Active
Human Leptin ELISA kit and BMI of all subjects was calculated in kg/m2 (weight in
kg and height in m). RESULTS: A highly positive linear correlation (R=0.754,
p<0.001) was found between BMI and serum leptin in unexplained infertile women,
which indicates a strong relationship between BMI and serum leptin. The variation
in serum leptin is explained by the independent variable, BMI. There was a
partial positive linear correlation between BMI and serum leptin in the control
group. Statistically there was no significant correlation (R=0.109, p=0.258)
between BMI and serum leptin in the control group. CONCLUSION: The present study
clearly demonstrates that level of leptin is higher in unexplained infertile than
in the fertile group, and also shows that a strong relationship exists between
BMI and serum leptin in the obese group. Serum leptin level was significantly
higher in obese than non-obese subjects. Thus, leptin is an important factor for
normal reproductive function. Obesity, the main cause of infertility may be
controlled by regulating the leptin concentration.
PMID- 28511458
TI - Maternal and Cord Blood Plasma sEng and TGF-beta1 in Patients with Hypertensive
Disorders of Pregnancy: A Pilot Study in a South Indian Population.
AB - INTRODUCTION: Hypertensive Disorders of Pregnancy (HDP) are one of the most
widespread complications of pregnancy that affects both mother and foetus. It has
been observed that in Preeclampsia, the release of soluble angiogenic factors
from the ischemic placenta into maternal plasma plays a crucial role in the
pathogenesis. AIM: To assess the plasma Soluble Endoglin (sEng) and Transforming
Growth Factor (TGF-beta1) levels in various types of HDP and to correlate the
levels of these markers with the pregnancy outcome. MATERIALS AND METHODS: A
total of 128 pregnant women were recruited and the study was carried out for a
period of three years. Cord blood and maternal blood plasma levels of sEng and
TGF-beta1 were analysed by ELISA kits in Control Pregnant Women (CPW),
Gestational Hypertension (GH), Early Onset Preeclampsia (EOPE), Late Onset
Preeclampsia (LOPE), and Eclampsia (E) during third trimester. The Gestational
Age (GA) at the time of delivery and Birth Weight (BW) of the baby also were also
evaluated. RESULTS: The circulating levels of maternal and cord blood sEng were
significantly higher in EOPE and E compared to CPW and GH. However, the maternal
and cord blood levels of TGF-beta1 were significantly lower in LOPE and E when
compared to CPW and GH. The GA and BW of the baby were found to be significantly
lower in EOPE and E compared to CPW, GH and LOPE. Also, a negative correlation
was observed between sEng levels with pregnancy outcome; GA and BW. And also, a
positive correlation was found between TGF-beta1 and pregnancy outcome.
CONCLUSION: A generalised angiogenic imbalance and poor birth outcomes were
observed in HDP. There is a spectrum of biochemical derangements related to
angiogenesis in GH, EOPE, LOPE and E.
PMID- 28511459
TI - A Comparison of 2-Methoxyestradiol Value in Women with Severe Preeclampsia Versus
Normotensive Pregnancy.
AB - INTRODUCTION: Preeclampsia is a pregnancy complication characterized by high
blood pressure and proteinuria. Endothelial dysfunction is a major theory
suggested as its aetiology. It is caused by anti-angiogenic condition
characterized by low Vascular Endothelial Growth Factor (VEGF). An estradiol
metabolite, called 2-Methoxy Estradiol (2-ME), is produced with the help of
Catechol-O-Methyltransferase (COMT). This substance has an important role in VEGF
expression. A 2-ME is suppressed in women with preeclampsia. AIM: To compare 2-ME
in women with severe preeclampsia and normotensive pregnancy. MATERIALS AND
METHODS: A total of 80 subjects qualified the inclusion and exclusion criteria,
were divided into two groups (40 each): the severe preeclampsia and the
normotensive pregnancy. Blood sample was collected and examined with the ELISA 2
ME kit (Cayman). The data were compared and calculated using Fisher-Exact test to
examine 2-ME differences between the two groups. RESULTS: Women age, parity, and
gestational age showed a non significant difference between both groups.
Nonetheless, the BMI before pregnancy and the history of preeclampsia in the past
pregnancy showed significant differences. In this study, the 2-ME value was lower
in the severe preeclampsia group compared to the normotensive. CONCLUSION: This
study concludes that 2-ME value in severe preeclampsia is lower than normotensive
pregnancy. A lower 2-ME value may indicate COMT not producing enough 2-ME which
in turn may cause the pre-eclampsia.
PMID- 28511460
TI - Cuff Closure by Vaginal Route in TLH: Case Series and Review of Literature.
AB - Total Laparoscopic Hysterectomy (TLH) represents one of the most performed
gynaecological procedures nowadays. The closure of the vaginal cuff is the most
diffucult part of TLH because of the difficulty of laparoscopic suturing
techniques. Our aim was to evaluate the efficacy and safety of vaginal cuff
closure by vaginal route on patients submitted to TLH. During the period between
January 2013 to December 2015 total number of 64 laparoscopic hysterectomy were
performed in our clinic. TLH and vaginal vault closure was performed as described
by Ghezzi for all patients. The length of cuff closure time and the frequency of
vaginal cuff-related complications were measured. Mean age was 48.1 (38-71)
years, mean parity was 2.6 (1-9). Most ranked indications for hysterectomy were
abnormal uterine bleeding and symptomatic leiomyoma. Average cuff closure time
was 6 (2-17) minute. In average 24 (2-36) month follow-up there were no vaginal
vault dehiscence. Transvaginal vaginal cuff closure seems to be safe, easy and
effective for total vaginal hysterectomy. Using vaginal route can significantly
reduce the length of closure time. This technique has comparable complication
rates with endoscopic suturing techniques.
PMID- 28511461
TI - Cervical Pregnancy Masquerading as an Incomplete Abortion- A Learning Lesson.
AB - Cervical pregnancy is a rare site of ectopic pregnancy compared to tubal. The
trophoblast implant into the cervical tissue and become a potentially dangerous
site of torrential haemorrhage. The widespread use of Ultrasonography (USG) has
led to a dramatic increase in the detection rates of extra uterine pregnancy. We
hereby report an interesting case of extra uterine pregnancy with a unique
situation where only a high index of suspicion prevented an iatrogenic mishap.
The patient was referred as a case of incomplete abortion with a documented
report of minimal retained products. Because of a high index of suspicion a serum
beta Human chorionic gonadotropin (hCG) was sent prior to deciding for discharge.
This indeed turned as a major change in the diagnosis of the case as the serum
beta hCG was elevated. On re-evaluation, we diagnosed it as a case of cervical
pregnancy which was successfully managed medically.
PMID- 28511462
TI - Story of a Giant Endometrial Polyp in Asymptomatic Postmenopausal Female.
AB - Endometrial polyps are localized overgrowth of endometrial glands and stoma
through the uterine cavity. They are associated with postmenopausal bleeding,
infertility and menorrhagia and are affected by unbalanced oestrogen therapy or
increased frequency of tamoxifen exposure. We report a case of giant endometrial
polyp in postmenopausal female without vaginal bleeding and hormone or drug use.
A 65-year-old, postmenopausal female P3L2 with hypertension and Diabetes Mellitus
(DM) came for routine health check-up. Her physical examination was normal.
Pelvic examination uterus was multiparous sized, mid positioned and bilateral
fornices were free. Patient was planned for hysteroscopic guided biopsy as her
Ultrasonography (USG) showed endometrial thickness to be 12.3 mm. On
hysteroscopy, there was hyperplastic endometrium with large endometrial polyp of
size 8.5 cm. Polypectomy was done and the same was sent for histopathological
evaluation. Report showed cystic hyperplasia without atypia. To summarize,
postmenopausal female will not always present with symptoms and USG can also
quite frequently miss the diagnosis, so proper evaluation is needed using
hysteroscopy which is gold standard for diagnosis and treatment of endometrial
polyp.
PMID- 28511463
TI - Unusually High Serum Levels of CA 19-9 in an Ovarian Tumour: Malignant or Benign?
AB - Carbohydrate antigen 19-9 (CA 19-9) is a tumour marker found to be elevated in
some ovarian tumours. We share our experience with a 55-year-old postmenopausal
lady with unusually high CA19-9 levels arising from a benign mucinous cystadenoma
of the ovary. The levels returned to normal eight weeks following staging
laparotomy and a total abdominal hysterectomy with bilateral salpingo
oopherectomy. This report shows rare and significant elevation of CA 19-9 levels
with benign mucinous cystadenomas of the ovary thus showing that women with
unusually elevated tumour markers may actually harbour benign disease. The tumour
markers should not be used to predict the malignant status of a tumour.
PMID- 28511464
TI - A Study to Assess the Functional Outcome of Decompression and Posterior Lumbar
Interbody Fusion of Low Grade Spondylolisthesis of Lumbar Vertebra.
AB - INTRODUCTION: Spondylolisthesis is defined as the forward displacement of one
vertebra over the vertebra below. It is often accompanied by spinal canal
stenosis and compression, which is the cause of all the symptoms. AIM: To assess
and study the functional outcome after decompression and Posterior Lumbar
Interbody Fusion (PLIF) of isthmic spondylolisthesis of lower lumbar vertebra and
to study the complications occurring with this technique. MATERIALS AND METHODS:
A prospective study was conducted in the Department of Orthopaedics in Justice KS
Hegde Charitable Hospital, Mangalore, Karnataka, India from March 2015 to August
2016. A total of 15 diagnosed patients with Grade I and II spondylolisthesis of
L4-L5 and L5-S1 vertebrae with no neurological deficits, between the age group of
25-50 were included in the study. An initial two months of conservative treatment
of back physiotherapy and flexion exercises was tried. Patients who did not
improve with the conservative therapy were taken up for surgery with consent.
Decompression and PLIF with bone grafting with interbody cage placement and
pedicle screw instrumentation was performed. The patients were discharged on
postoperative day 10 after suture removal. They were reviewed at postoperative
day 10, week six and week 24. The scoring of the functional outcome of the back
was done as per the Modified Oswestry low back pain Disability Questionnaire. The
statistical analyses were done using the repeated measures ANOVA, SPSS version
20. RESULTS: The mean Modified Oswestry low back pain Disability score
preoperatively was noted to be 42.87+/- 3.46 points. The mean Modified Oswestry
low back pain Disability score at postoperative day 10 was noted to be 36.93+/
3.75 points. The mean Modified Oswestry low back pain Disability score at
postoperative week six was noted to be 28.47+/-3.70 points. The mean Modified
Oswestry low back pain Disability score at postoperative week 24 was noted to be
24.27+/-3.01 points. Improvement in the Modified Oswestry low back pain
Disability scores was noted during the follow ups. Foot drop was noted in two
cases postoperatively which improved during the final follow up with
physiotherapy. CONCLUSION: Decompression and PLIF is noted to produce good to
satisfactory functional results in cases of isthmic spondylolisthesis of lower
lumbar vertebra.
PMID- 28511465
TI - Digging Deeper into the Patello - Femoral Joint: Patello - Femoral Composite - A
New Dimension for Overstuffing of Patello - Femoral Joint.
AB - INTRODUCTION: Patello-femoral complications are the most common complications in
postoperative Total Knee Arthroplasty (TKA) patients especially overstuffing of
Patello - Femoral Joint (PFJ). So, to study the effects of overstuffing of PFJ in
postoperative TKA patients we put forth a new dimension - "PATELLO - FEMORAL
COMPOSITE (PFC)". This is the maximum distance between anterior cortical line of
femur shaft and the anterior cortex of patella with knee in full extension. AIM:
To calculate chances of overstuffing of PFJ in postoperative TKA patients and
document the effect of overstuffing of PFJ on the passive knee Range of Motion
(ROM) in post- op TKA patients. MATERIALS AND METHODS: This was a prospective
observational study which included 51 consecutive primary TKAs. Preoperative and
postoperative (24 weeks) passive knee ROM was measured. Preoperative and
postoperative radiological parameters {PFC, Anterior Femur Offset (AFO), Patellar
thickness (PT)} was recorded using Computed Tomography (CT) Scanogram image of
patient in lateral view with knee in full extension and perfect overlap of both
femur condyles, using DICOM format of the CT Scanogram image on the DICOM viewer.
RESULTS: The postoperative PFC was more than its preoperative-value in 80.39%
TKAs. Patients who had increased postoperative PFC had significantly less
preoperative AFO. Female patients in our study had significantly less
preoperative AFO compared to males. Thus, we deduced that female patients with
lesser preoperative AFO undergoing TKA had increased postoperative PFC than male
patients. PFC not only accounted for the overstuffing of the PFJ because of the
patellar component, but also because of the femoral component; thus was a better
measure of PFJ overstuffing compared to isolated PT. Passive knee ROM in the
postoperative TKA patients approximately decreased by 2 degrees for every 1 mm
increase in PFC compared to its preoperative-value in the patients with PFJ
overstuffing. CONCLUSION: We conclude that overstuffing of the PFJ in
postoperative TKA is present in 80.39% patients. Higher chances of postoperative
PFJ over stuffing are present in female patients and those with thinner anterior
cortex of distal femur. Postoperative passive knee ROM decreases significantly in
patients with postoperative PFJ overstuffing (Every 1 mm increase in the
postoperative PFC, passive knee ROM decreased by approximately 2 degrees).
PMID- 28511466
TI - Management of Cubitus Varus Deformity in Children by Closed Dome Osteotomy.
AB - INTRODUCTION: Supracondylar fractures are the most common elbow injuries in
skeletally immature children between 5-10 years of age and cubitus varus
deformity is the most common late complication. Cubitus varus or bow elbow or
gunstock deformity is the result of malunion occurring as a complication of
supracondylar fracture of the humerus. Various type of corrective osteotomies are
used of which lateral closed wedge French osteotomy is commomly used which has
its own complications like lateral condylar prominence, unsightful scar and
limitation of movement. Closed dome osteotomy is a technique which overcomes
these complications. This surgery is done with simple readily available
instruments in the orthopaedic operation theatre with no special requirements for
instrumentation. AIM: This study was done to study the results of closed dome
osteotomy for correction of cubitus varus deformity, after malunited
supracondylar fracture of humerus in children. MATERIALS AND METHODS: This study
included 25 children of either sex with malunited supracondylar fracture of
distal humerus having cubitus varus deformity admitted in orthopaedics
department. After appropriate pre operative assessment, closed dome osteotomy was
done and post operatively X-ray of patients was taken and carrying angle and
Lateral Condylar Prominence Index (LCPI) were calculated. Patients were re
assessed at complete union and results were calculated as per Mitchell and Adams
criteria. RESULTS: In our study of 25 patients, 68% were males, 32% were females.
Majority (84%) of patients were in the age group of 5-10 years. Carrying angle
post operatively was 0-10 degrees valgus in 64% of patients while 36% had 10-20
degrees valgus. LCPI changed post operatively ranging from +5.0% to -10.7%,
average -2.75%. Decrease in LCPI had better cosmetic appearance. Range of motion
post operatively increased or remained same as previous full motion in 84% of the
patients. Union occurred in all patients by eight weeks. Few complications were
seen. Results according to Mitchell and Adams criteria were excellent in 88% and
good in 12%; while no poor results were recorded. CONCLUSION: The results
obtained in our study concluded that closed dome osteotomy is safe and effective
treatment for the correction of cubitus varus deformity with few minor
complications.
PMID- 28511467
TI - Chaput Tubercle Fracture in an Adult- A Rare Case Report.
AB - Chaput tubercle fracture occurs at the antero-lateral position of the distal
tibia in adult as a counterpart of adolescent Tillaux fracture. It is a case of
adult male which presented to us with onset of acute pain, swelling and
restricted movements of ankle after a road side accident. A clinical diagnosis of
Chaput tubercle fracture was established after a CT-scan. The displaced fracture
was managed by open reduction and internal fixation by screw. At the end of
follow up, the foot and ankle ability score measured. Through this case report we
convey that Chaput tubercle fracture in an adult is a rare entity.
PMID- 28511468
TI - Tuberculosis of Acromioclavicular Joint.
AB - Tuberculosis (TB) arthritis accounts for approximately 1%-3% of all cases of TB
and for approximately 10%-11% of extra pulmonary cases. Isolated
acromioclavicular joint TB has been reported rarely with varied presentations as
case series of one to three cases none of them being large studies. In our case,
patient presented with pain in left shoulder since one month. Patient was
investigated and was diagnosed to have acromioclavicular joint TB on basis of
positive Acid Fast Bacilli (AFB) stain and cytology. Patient recovered well with
antitubercular therapy. Thus, it is important to send Ziehl-Neelsen (ZN) stain in
all cases in an endemic country like India.
PMID- 28511469
TI - Clinical Profile and Outcome of Newborns with Acute Kidney Injury in a Level 3
Neonatal Unit in Western India.
AB - INTRODUCTION: Acute Kidney Injury (AKI) is a serious condition in neonatal care.
It complicates the management necessitating the restrictive use of medications.
AIM: To evaluate clinical profile, identify associated and prog-nostic factors in
newborns with AKI. MATERIALS AND METHODS: This was a case control study done
between January 2008 to January 2010. Total 1745 newborns were admitted, of which
74 babies had AKI. It was defined as serum creatinine >1.5mg/dl. Control group
was selected randomly from the hospital numbers of the newborns derived from the
electronic registry with serum creatinine below 1.5 mg/dl. Demographic variables
like birth weight, gender, gestational age, admission age, growth restriction,
Apgar scores, electrolyte levels; and common clinical conditions like asphyxia,
sepsis, meningitis, persistent pulmonary hypertension, Necrotizing Enterocolitis
(NEC), mechanical ventilation, congenital heart disease; were compared amongst
the two groups. Information was obtained from the admission register, admission
files, labor register of obstetrics and gynaecology department and electronic
registry. Chi square/independent sample t-test as applicable and logistic
regression were used to establish an association of various factors and outcome
with AKI. RESULTS: The incidence of AKI in our study was 4.24%. Demographic
variables more common in AKI group were inborn (p=0.011), male gender (p=0.032),
term gestation (p=0.001), Appropriate for gestational age (0.001), higher birth
weight (p<0.001), full term (p<0.001), sepsis (p<0.001), NEC (p=0.042), low ApGAR
scores at one minute (p=0.011) and five minute (p=0.003). However, on
multivariate logistic regression only male gender [Odds Radio (OR)=2.84,
Confidence Interval (CI)=1.12-7.21] and Sepsis (OR=14.46, CI=4.5-46.46) were
associated with AKI. Respiratory distress syndrome was more prevalent in the
control group (p<0.003). No need of mechanical ventilation and absence of shock,
improved the survival. CONCLUSIONS: AKI continues to be of clinical significance
in neonatal intensive care. Further studies are needed to evaluate newer
associations (like male gender and low APGAR scores).
PMID- 28511470
TI - Study on Steroid Induced Ocular Findings in Children with Nephrotic Syndrome.
AB - INTRODUCTION: Long term use of corticosteroids in Nephrotic Syndrome (NS) is
associated with ocular complications such as Posterior Subcapsular Cataract
(PSC), glaucoma, increased intra-ocular pressure, ptosis, mydriasis, eyelid skin
atrophy, keratisis, thinning of cornea and sclera, repeated hordeolum
exacerbations. AIM: To determine ocular abnormalities in children with NS and
their association with steroid dosing and duration. MATERIALS AND METHODS:
Hundred patients with NS in the age group of 2-18 years, with no evidence of
other systemic disease, were considered for the study. Group I included cases
(66) who took standard steroid regimen for first episode of NS. Group II included
cases (34) who took steroid irrationally (daily basis for long time) other than
standard regimen. Steroid induced ocular complications were compared in both
groups after detailed ophthalmological examination. Statistical analysis was done
using Statistical Package for Social Science (SPSS-20.0). RESULTS: Ocular
abnormalities were found in 12 patients out of 66 in Group I (18%) and 16
patients out of 34 patients in Group II (47%). Out of 12 patients of Group I who
had ocular problems, three had myopic astigmatism, eight patients had PSC and one
had temporal disc pallor. While in Group II, out of 16 patients who had ocular
complications, two patients had raised intra ocular pressure and two patients had
myopic astigmatism and 12 patients had posterior sub capsular cataract. The
difference in mean cumulative steroid doses in both groups was statistically
significant but no such difference was there between duration of steroid intake
in both group. CONCLUSION: Our study concluded that ocular complications were
more common in patients with irrationally steroid intake and cumulative steroid
dose intake was also significantly higher in same patients.
PMID- 28511471
TI - Internet Based Obesity Prevention Program for Thai School Children- A Randomized
Control Trial.
AB - INTRODUCTION: Internet based obesity prevention program is one approach in
learning strategies to improve healthy behaviour. It has been advocated as one
strategy to address the rising prevalence of childhood obesity; however, their
efficacy is not seen consistently. AIM: The purpose of this study was to assess
the efficacy of internet based obesity prevention program in Thai school
children. MATERIALS AND METHODS: Healthy children studying in public schools in
one township of central Thailand were randomly assigned to either the
intervention (internet based) program or the control group. Anthropometric
characteristics were recorded at baseline and for the next four following months
at monthly intervals. Changes in the percentage of overweight/obese children and
changes in BMI at the end of study were considered as the primary and secondary
outcome, respectively. RESULTS: A total of 217 children, mean age of 10.7 years,
were included into the final analysis. Baseline anthropometric parameters and
percentages of overweight/obesity were not significantly different between
groups. At the end of the study, the control group had a higher percentage of
overweight/obesity than the intervention group (56.6% vs. 39.6%, respectively; p
value=0.009). Children in the control group had a significantly higher increase
in net BMI gains than those in the intervention group (1.24kg/m2 vs. 0.40kg/m2, p
value=0.027). The intervention group had no changes in BMI z-score (-0.001, 95%CI
-0.19 to 0.18, p-value=0.988), contrary to those in the control group, which had
significant gain of BMI z-score at the end of study (0.45, 95%CI 0.27 to 0.63, p
value<0.001). CONCLUSION: Internet the based obesity prevention program was
effective in modifying anthropometric outcome and helped to address the rising
prevalence of overweight and obese status in Thai children.
PMID- 28511472
TI - Short Term Unscheduled Revisits to Paediatric Emergency Department - A Six Year
Data.
AB - INTRODUCTION: Reviewing the reasons for return visits within 24 hours is a very
important method of determining possible problems of emergency health care.
Several causes stay behind unscheduled emergency return visits. Therefore,
identifying these factors is crucial to set strategies in order to decrease the
number of unnecessary visits. AIM: To define the characteristics of the patients
returning to the Paediatric Emergency Department (PED) within 24 hours via
determining rate, number and demographic data of patients. MATERIALS AND METHODS:
The present study design involves retrospective data collection of patients who
returned to PED within 24 hours after being discharged. Data was included over
six year period and was collected from July 1, 2010 to June 30, 2016. The data
was analysed with SPSS17.0 statistical package for windows. RESULTS: A total of
1994 patients returned to PED within 24 hours from July 1, 2010 to June 30, 2016.
The most common group of revisiting patients were toddlers (aged 0-2-year old),
n=1168 (58.5%), and the least number represented young adolescents (aged 15-18
year old), n=82 (4.1%). Number of patients returning to PED in 24 hours has
significantly increased within years from approximately 90 patients to 720
(p<0.05). This increase in number was observed in all and each age group (from 0
18 years of age) without any exception. Seasonal distribution of the patients
showed no significant difference (p>0.05) for each age, but again, presented
definite negative correlation with age (the older is the patient group, the less
is the number of revisits). The most common time for revisits was 17-24 hours
after first discharge from PED, n=1277 (64.04%). CONCLUSION: The number of return
visits is increasing over the years. The younger the patient is, more likely is
the risk of unscheduled revisit to PED. Most of the patients returned to PED in
17 to 24 hours after discharge.
PMID- 28511474
TI - Correspondence: Predictors of Mortality in Paediatric Myocarditis.
PMID- 28511473
TI - Phytotherapy with Hordeum Vulgare: A Randomized Controlled Trial on Infants with
Jaundice.
AB - INTRODUCTION: Jaundice is one of the most common causes of admission to hospital
in newborns which is often associated with several complications. AIM: The
present study was conducted to evaluate the effect of H. vulgare in reducing
jaundice. MATERIALS AND METHODS: In this double-blind, randomized controlled
trials 70 term infants hospitalized due to jaundice in 2014 were enrolled.
Control group was treated with full-time phototherapy alone using LED except when
the infants were breastfed and case group with phototherapy, as per the protocol
in the control group, along with and topical H. vulgare seed flour three times a
day. Data were analysed using and analysis of covariance (ANCOVA) and paired t
test in SPSS version 16.0. RESULTS: There was a significant difference in mean
indirect bilirubin level between the two groups p<0.05, such that the mean
indirect bilirubin level was higher in the control group. Furthermore, no
significant difference was seen in direct bilirubin level between the two groups
at discharge p>0.05. CONCLUSION: H. vulgare flour can cause decrease in indirect
bilirubin. Because the rate of decrease in indirect bilirubin can be effective in
preventing severe complications due to bilirubinemia, H. vulgare can be used as a
complementary therapy to treat jaundice.
PMID- 28511475
TI - Colour Doppler Evaluation of Extracranial Carotid Artery in Patients Presenting
with Acute Ischemic Stroke and Correlation with Various Risk Factors.
AB - INTRODUCTION: Stroke is defined as an abrupt onset of neurologic deficit due to
vascular cause. It is one of the leading causes of mortality and morbidity all
over the world making early diagnosis and treatment inevitable. Lesions of extra
cranial carotid arteries are implicated in majority of cases of acute ischemic
stroke. Carotid Doppler is a non-invasive imaging technique, with sensitivity
approaching that of angiography. Computed Tomography (CT) plays a major role to
assess the site and nature of the lesion in patients with acute ischemic stroke.
AIM: To evaluate the role of carotid Doppler sonography in patients presenting
with acute ischemic stroke and find association between carotid artery stenosis
and risk factors such as diabetes mellitus, hypertension, hyperlipidemia, smoking
and age. MATERIALS AND METHODS: The present study was conducted on 50 patients.
CT scan was done to diagnose acute ischemic stroke in patients who presented to
emergency medicine with symptoms of acute ischemic stroke. Retrospectively CIMT
and plaque characterization were done by gray scale ultrasound. Site and severity
of stenosis were assessed on colour Doppler. All these findings were correlated
with clinical presentation and risk factors. The collected data was statistically
analyzed and multivariant logistic regression (R-value) test of significance was
applied by using SPSS 16.0 version software. RESULTS: On carotid Doppler, ICA/CCA
PSV ratio was good predictor of stenosis and ratio above three indicates
significant stenosis (>60%). Carotid bulb was most common location of plaque
formation. Hypertension and diabetes were the most prevalent risk factors for
cerebral ischemic stroke. Out of total 50 patients, 32 had hypertension (64%) and
22 had diabetes (44%). Hypertension and hyperlipidemia showed maximum mean R
values (0.275 and 0.048 respectively) and positive correlation with stenosis and
increased CIMT in acute ischemic stroke patients. CONCLUSION: The present study
highlights the importance of Doppler sonography in acute ischemic stroke patients
through surveillance of atherosclerosis.
PMID- 28511476
TI - Magnetic Resonance Imaging in Mixed Mullerian Tumour: Report of Two Cases.
AB - Malignant Mixed Mullerian Tumours (MMMTs) or carcinosarcomas of uterus are rare
aggressive tumours of mesenchymal origin. It is associated with high incidence of
lymphatic, pulmonary and peritoneal metastasis. We hereby present two cases of
mixed mullerian tumour. Case-1 was a 60-year-old post menopausal woman who had
come with complaint of metrorrhagia and a protruding mass in the vagina. Case-2
was of a 54-year-old post-menopausal woman who came with complaints of heavy
vaginal bleeding, pelvic pain since two months. For the assessment of these
tumours Magnetic Resonance Imaging (MRI) is preferred imaging modality due to
excellent tissue contrast to detect the myometrial invasion, local extent and
staging. Preoperative differentiation of mullerian tumour with endometrial
carcinoma is important as both have different treatment.
PMID- 28511477
TI - Inferior Vena Cava Agenesis: A Rare Cause of Pelvic Congestion Syndrome.
AB - Complete absence of Inferior Vena Cava (IVC) is a rare anomaly with a reported
incidence of 0.0005% to 1%. This is often asymptomatic with incidental detection
during cross-sectional imaging. It may also present with deep venous thrombosis,
pulmonary thromboembolism or compressive symptoms in form of nerve root
compression. Pelvic Congestion Syndrome (PCS) is an increasingly recognized
entity with well laid out diagnostic criteria and evolving management protocols.
Complete absence of IVC is a rare cause of pelvic congestion syndrome. We present
a case of young female presenting with symptoms typical of pelvic venous
congestion who was found to have complete absence of IVC as the underlying cause.
She also had associated small left kidney with compensatory hypertrophy of the
right kidney which is another rare association.
PMID- 28511478
TI - Recognition of Small Airways Obstruction in Asthma and COPD - The Road Less
Travelled.
AB - The small airways, once regarded as the silent zone in the air conducting system
of the lungs are now known to be one of the initial sites of involvement in
diseases like asthma and Chronic Obstructive Pulmonary Disease (COPD).
Identification of the involvement of distal airways in these diseases is often
difficult to assess, clinically as well as by conventional pulmonary function
tests and therefore, usually remains undiscovered in early stages. Early
recognition of their involvement in asthma and COPD and timely management may
reduce long term morbidity in these conditions. This article aims to highlight
the relatively lesser recognized facts about small airways involvement in asthma
and COPD and role of imaging and newer modalities for detection.
PMID- 28511479
TI - Extramedullary Haematopoiesis Presenting as an Adrenal Mass.
PMID- 28511480
TI - Azygos Lobe - A Rare Anatomical Variant.
PMID- 28511481
TI - Relationship of on Admission Hypocalcaemia and Illness Severity as Measured by
APACHE-II and SOFA Score in Intensive Care Patients'.
AB - INTRODUCTION: Hypocalcaemia is very much prevalent in critically ill patients yet
very less is known about its association with severity of illness. Acute
Physiology and Chronic Health Evaluation (APACHE) and Sequential Organ Failure
Assessment (SOFA) are two commonly used and validated scoring tool used to assess
the severity of illness in critically ill patients. AIM: To analyze the relation
of on admission hypocalcaemia with severity of illness as measured by APACHE-II
and SOFA scores. MATERIALS AND METHODS: After institute approval, 111 patients
admitted during May to June 2016 were evaluated. Age, sex, on admission, ionized
calcium (iCa0) levels, first day APACHE-II and SOFA scores were collected. Data
were then divided in different classes based on iCa0 levels (i.e.,
normocalcaemic, mild, moderate and severe hypocalcaemic), APACHE-II and SOFA
scores and their relationship was assessed using INSTAT software (GraphPad
Software, Inc, La Zolla, CA, USA) with appropriate statistical tests. RESULTS:
Seventy eight (70.27%) patients were having hypocalcaemia on admission (<1.15
mmol/L). The mean APACHE-II score of normocalcaemic patients were significantly
(p<0.05) lower as compared to moderate and severe hypocalcaemic patients (15.57+/
6.85 versus 21.72+/-6.37 and 15.57+/-6.85 versus 22.34+/-7.53, respectively). The
mean iCa0 level in patients with APACHE-II > 20 were significantly lower than
patients with APACHE-II < 9 (0.88+/-0.26 versus 1.09+/-0.24, p <0.05) but the
mean iCa0 level in patients with SOFA > 9 were not significantly lower than
patients with SOFA < 4 (0.99+/-0.41 versus 1.04+/-0.23, p > 0.05). The relative
risk of on admission hypocalcaemia across increasing illness severity was also
not statistically significant. Both relative risk of mortality and length of ICU
stay were higher in on admission moderate hypocalcaemic patients as compared to
normocalcaemic but the difference was not statistically significant. CONCLUSION:
On admission, hypocalcaemia has inconsistent correlation with increasing illness
severity in adult intensive care patients. iCa0 of 0.81-0.90 mmol/L appears to
have maximum deleterious effect with regard to mortality and length of ICU stay.
PMID- 28511482
TI - Effect of Ketofol on Pain and Complication after Caesarean Delivery under Spinal
Anaesthesia: A Randomized Double-blind Clinical Trial.
AB - INTRODUCTION: Pain is the key concern of women after caesarean delivery that may
interfere with breastfeeding. AIM: The aim of this study was to assess effect of
ketofol (ketamine/propofol combination) on pain and complication after caesarean
delivery under spinal anaesthesia. MATERIALS AND METHODS: In this randomized
double-blind clinical trial, 92 parturient scheduled for elective caesarean
delivery under spinal anaesthesia were included. The simple random sampling
method was used to place subjects in four groups of ketamine (0.25 mg/kg),
propofol (0.25 mg/kg), ketofol (25 mg ketamine plus 25 mg propofol) and placebo
(saline). The drugs were administered intravenously immediately after clamping
the umbilical cord. Visual Analog Scale (VAS) was used to determine the intensity
of pain. Complications after surgery including shivering, nausea and vomiting as
well as onset of breastfeeding were recorded. RESULTS: The mean score of pain,
morphine consumption and time of breastfeeding in the ketofol group were
significantly lower than other groups at various intervals (p<0.05, p<0.001). The
frequencies of shivering, nausea, vomiting, retention and pruritus in the ketofol
group were significantly lower than other groups (p<0.001, p<0.05). CONCLUSION:
The effective role of ketofol on reducing pain and complication after caesarean
delivery indicated that it can be considered as a safe and alternative drug in
these patients.
PMID- 28511483
TI - A Study of Morbidity and Cost of Peripheral Venous Cannulation in Neonates
Admitted to Paediatric Surgical Intensive Care Unit.
AB - INTRODUCTION: Peripheral venous access in sick neonates is indicated for
administration of fluids, drugs or nutrients. AIM: We conducted an audit of
peripheral venous access in neonates admitted to paediatric surgical intensive
care unit to study the morbidity, time spent on cannulation and cost with its
use. MATERIALS AND METHODS: One hundred consecutive neonates requiring hospital
admission to paediatric surgical intensive care unit in a period of one year were
included in the study. Peripheral venous access was secured in all patients. We
conducted an audit for the number of venipuncture sites, wastage of cannulae,
cost, time spent on cannulation and morbidity with its use. Neonates were divided
into three groups depending on their surgical intervention. Namely, Group A
(thoracic procedures), Group B (bowel surgery) and Group C (other surgery and non
operative cases). RESULTS: In Group A, mean venepuncture sites were 10.66, used
cannulae were 5.6, wasted cannulae were 4.3, total cost of cannulation was 870
rupees and 93.78 minutes were spent in cannulation per neonate. In Group B, mean
venepuncture sites were 7.58, used cannulae were 4.35, wasted cannulae were 2.59,
total cost of cannulation was 603 rupees and 59.85 minutes were spent in
cannulation per neonate. In Group C mean venepuncture sites were 2.78, used
cannulae were 2.9, wasted cannulae were 0.57, total cost of cannulation was 232
rupees and 26.51 minutes were spent in cannulation per neonate. Thrombophlebitis
severity was greater in neonates who had longer ICU stay and ventilator dependent
days. CONCLUSION: Peripheral venous cannulation of longer duration is costly,
time consuming, and associated with significant neonatal morbidity. It may be
worthwhile to consider alternative vascular devices such as peripherally inserted
central catheters or central venous catheters in such situations.
PMID- 28511484
TI - Efficacy of Structured Yoga Intervention for Sleep, Gastrointestinal and
Behaviour Problems of ASD Children: An Exploratory Study.
AB - INTRODUCTION: Autism Spectrum Disorder (ASD) is a neuro developmental disorder
which appears at early childhood age between 18 and 36 months. Apart from
behaviour problems ASD children also suffer from sleep and Gastrointestinal (GI)
problems. Major behaviour problems of ASD children are lack of social
communication and interaction, less attention span, repetitive and restrictive
behaviour, lack of eye to eye contact, aggressive and self-injurious behaviours,
sensory integration problems, motor problems, deficiency in academic activities,
anxiety and depression etc. Our hypothesis is that structured yoga intervention
will brings significant changes in the problems of ASD children. AIM: The aim of
this study was to find out efficacy of structured yoga intervention for sleep
problems, gastrointestinal problems and behaviour problems of ASD children.
MATERIALS AND METHODS: It was an exploratory study with pre-test and post-test
control design. Three sets of questionnaires having 61 questions developed by
researchers were used to collect data pre and post yoga intervention.
Questionnaires were based on three problematic areas of ASD children as mentioned
above and were administered to parents by teachers under the supervision of
researcher and clinical psychologists. Experimental group was given yoga
intervention for a period of 90 days and control group continued with school
curriculum. RESULTS: Both children and parents participated in this intervention.
Significant changes were seen post yoga intervention in three areas of problems
as mentioned above. Statistical analysis also showed significance value of 0.001
in the result. CONCLUSION: Structured yoga intervention can be conducted for a
large group of ASD children with parent's involvement. Yoga can be used as
alternative therapy to reduce the severity of symptoms of ASD children.
PMID- 28511485
TI - Spiritual Well-Being and Associated Factors with Relapse in Opioid Addicts.
AB - INTRODUCTION: Opioid dependence relapse is a complex and multidimensional
problem, and lack of spiritual well-being is a major concern in opioid addicts.
AIM: This study was conducted to determine spiritual well-being and factors
associated with relapse among opioid addicts. MATERIALS AND METHODS: This cross
sectional study was conducted from April 2015 to September 2015. According to
purposive sampling, 312 eligible addicted patients were enrolled in the study.
The patients had at least an attempt of detoxification in the past six months and
referred to an outpatient detoxification clinic in Shahrekord (Southwest, Iran).
They completed Paloutzian and Ellison's Spiritual Well-being Scale. A researcher
developed questionnaire consisting of demographic characteristics and 20
questions about associated factors with relapse was administered. Data were
analysed by version 16.0 (SPSS Inc.,Chicago, IL) using one-way ANOVA, Pearson's
correlation test, chi-square, Friedman test, and student's t-test. RESULTS: The
most important factors associated with opioid dependence relapse consist of
relation with an addict friend, unemployment, living expenses, family conflicts,
and somatic pain. In the present study, 157 patients had never experienced
relapse while the mean of relapse in the rest participants was (3.25+/-1.53)
times. Furthermore, the addicted patients with relapse had significantly lower
scores of spiritual well-being and its subscales compared with non-relapse
patients (p<0.001). CONCLUSION: The findings of the present study indicate the
necessity of paying attention to spiritual well-being, family and economical,
personal, and occupational factors as crucial factors in opiate addiction
relapse.
PMID- 28511486
TI - A Review on Detection and Treatment Methods of Sleep Apnea.
AB - This paper presents a review on detection and treatment methods of sleep apnea.
Sleep apnea is the most common type of breathing-related sleep disorder. It
manifests in a variety of behaviours from teeth grinding to night terrors as
involuntary night-time events. The most common sleep disorders are narcolepsy,
hypersomnia, sleep talking, sleep walking, and bedwetting. Sleep apnea
(somnipathy) is a serious sleep disorder that pauses breathing while sleeping.
Breathing pauses occur 30 times or more during sleep and it lasts for few seconds
to minutes, when normal breathing starts after this pause. Untreated sleep apnea
patients stop breathing, which happens up to hundreds of times during sleep that
ultimately results in atrial fibrillation, cardiac arousal, stroke, brain tumor
and other vascular diseases at the age of 65 that causes death. Smokers are at a
greater threat for sleep apnea. Several studies have suggested that a person who
smokes more than two packs a day has 40 times the risk of sleep apnea then
nonsmokers. This review includes the discussion about detection of sleep apnea
from heart rate and respiratory events. The published literature of sleep apnea
and methods of treatment are also discussed.
PMID- 28511487
TI - A Comparative Study of Liquid Nitrogen Cryotherapy as Monotherapy versus in
Combination with Podophyllin in the Treatment of Condyloma Acuminata.
AB - INTRODUCTION: Condyloma Acuminata (CA) is a common viral sexually transmitted
disease. Although various treatment modalities are available for treating CA, but
none of them can achieve 100% response rate. In a search for better response rate
and less recurrence rate, the combination of cytotoxic agent Podophyllin with
ablative liquid nitrogen cryotherapy was evaluated over cryotherapy alone. AIM:
To evaluate the synergistic effect of Podophyllin as a chemotherapeutic adjunct
to an ablative therapy of liquid nitrogen cryotherapy versus liquid nitrogen
cryotherapy alone in the treatment of CA. MATERIALS AND METHODS: Sixty patients
with multiple CA were randomly assigned to two groups in the study. Thirty
patients in group A received double freeze thaw cycle of 25 seconds of liquid
nitrogen cryotherapy. Thirty patients in Group B were subjected to liquid
nitrogen cryotherapy in a similar manner followed by application of not more than
0.5 ml of 25% Podophyllin solution. All patients were followed up at 1, 4, 8, 12
and 24 weeks after the treatment to monitor the response to therapy and
evaluation for any recurrence. When the number of unresponsive lesions were more
than 30% of original lesions at 4 weeks follow-up, then the whole procedure was
repeated again. RESULTS: The complete response rate and the recurrence rate in
the Group B in our study were comparable to Group A as the difference was
statistically insignificant. But the differentiating point was that the similar
results were obtained in Group B with an average1.2 sessions per patient in
comparison to an average of 1.67 sessions per patient in Group A. CONCLUSION:
Cryotherapy represents a simple, safe and effective regimen for the treatment of
multiple CA which in combination with Podophyllin is even more effective as a
single session procedure; thereby shortening the treatment regimen.
PMID- 28511489
TI - Micronucleus Assay in Urothelial Cells in Cancer Cervix.
AB - INTRODUCTION: Cancer ranks third among the ten leading global causes of death. To
evaluate the genotoxic risks, observed as DNA damages, can be assessed by
Micronucleus (MN) test. AIM: To identify the occurrence of MN in normal and
cancer cervix and find the correlation between MN and stage of cancer. MATERIALS
AND METHODS: A total of 60 females were included in the study and visual
examination of the cervix was done. Based on the examination two groups were
formed: A- Normal cervix (n-23) and B- Presence of erosion or growth or ulcer
etc., in cervix (n-37). Midstream urine sample was collected and centrifuged from
the cases after getting the informed consent. Slides were prepared from the
pellet, were fixed in methanol, glacial acetic acid fixative and stained with
Giemsa and May Grunwald stain. Statistical analysis was done by student's t-test
and chi-square test. RESULTS: A linear association was noted between the mean MN
count and cancer cervix stage. Almost 18.2% of the Group A cases had significant
MN count. Sensitivity and specificity of MN count in Group A was 83.8% and 82.6%
respectively. The efficiency was 83.3%. CONCLUSION: A statistically significant
MN count was seen in the different stages of cancer cervix. There are cases who
had normal findings on visual inspection of cervix but with significant MN count
are prone for malignant transformation. MN assay is an easy, non-invasive, cost
effective method and can be used as a screening test for a large population.
PMID- 28511488
TI - Comparative Efficacy and Safety of Ebastine 20 mg, Ebastine 10 mg and
Levocetirizine 5 mg in Acute Urticaria.
AB - INTRODUCTION: Acute and chronic urticaria can result in severely impaired quality
of life from pruritus and associated sleep lessness, as well as anxiety and
depression. Various treatment modalities are available out of which second
generation non sedating H1 antihistamines e.g., fexofenadine, loratidine,
desloratadine, cetirizine, levocetirizine, ebastine etc., are used as the first
line treatment. AIM: To compare the safety and efficacy of ebastine 20 mg,
ebastine 10 mg and levocetirizine 5 mg in the patients of urticaria. MATERIALS
AND METHODS: A longitudinal study was conducted in dermatology Outpatient
Department (OPD) of Adesh Institute of Medical Sciences and Research, Bathinda,
India. A total of 150 patients between the age group 10-70 years, both men and
women having urticaria were enrolled and divided into three groups of 50 each.
Group A was given ebastine 20 mg OD, Group B was given ebastine 10 mg OD and
Group C was given levocetirizine 5 mg OD. The patients were asked to scale their
severity of disease over a period of follow up based on Urticarial Activity Score
7 (UAS7). RESULTS: The mean age of patients was 32.82 years. The mean UAS 7 score
at the end of 4th week was 1.08 with ebastine 20 mg, 1.98 with levocetirizine 5
mg and 3.98 with ebastine 10 mg. In group A, 40 out of 50 patients (i.e., 80%),
in Group B 25 out of 50 (i.e., 50%) get UAS7=0 and in Group C, 35 (i.e., 70%)
patients who got relieved of symptoms at the end of treatment. When the scores
were redefined and categorized under relieved and not relieved, and comparison
done between all three groups, then there was a significant difference in the
number of patients getting relieved, with p<0.001 (highly significant).
Levocetirizine 5 mg had shown more side effects like dryness of mouth and
sedation as compare to ebastine irrespective of dosage. The comparison made
between the number of patients developing side effects among the groups was
highly significant (p<0.001) for all the side effects. CONCLUSION: Ebastine 20 mg
is found to have superior efficacy for treatment of Urticaria as compared to
ebastine 10 mg but with levocetirizine 5 mg the results were almost similar.
Tolerability of ebastine 20 mg is similar to ebastine 10 mg but with
levocetirizine 5 mg there were more side effects and less tolerability.
PMID- 28511490
TI - Primary Orbital Follicular Lymphoma: A Case Report and Review.
AB - Orbital Lymphomas (OL) constitute a heterogeneous group of lymphoproliferative
disorders of the orbit. They are predominantly of the Mucosa-Associated Lymphoid
Tissue (MALT) subtype. Radiotherapy is the mainstay of treatment in localized
orbital tumours, while chemotherapy is reserved for systemic disease. Authors
report a case of a primary orbital lymphoma of follicular subtype (stage 1E) in a
54-year-old female managed by surgery and adjuvant radiotherapy.
PMID- 28511491
TI - Choroidal Metastasis as Initial Presentation in Adenocarcinoma of Lung: A Case
Report.
AB - Vision impairment as an initial presentation detecting choroid metastasis in
primary lung cancer is rare. Prevention or treatment of visual loss and
improvement in quality of life can be achieved by treatment of intraocular
metastasis. The survival of the patient in choroid metastasis with lung primary
is poor with the median survival being 3.3 months. However, proper treatment may
increase the quality of life and survival to an extent. We report a case of
adenocarcinoma of lung in a female patient, presented initially with visual
impairment as a result of choroidal metastasis and treated with external beam
radiotherapy for choroidal metastasis followed by palliative chemotherapy. The
patient was survived with improved vision and quality of life since last 12
months of diagnosis.
PMID- 28511492
TI - Cardiac Myeloid Sarcoma: Review of Literature.
AB - Granulocytic Sarcomas (GS) also called as Myeloid Sarcomas (MS) or chloromas are
the representatives of extramedullary infiltrates of immature myeloid cells
including myeloblasts, promyelocytes and myelocytes. Primary cardiac malignancies
per se are rare and infiltration of cardiac muscles by secondary malignant cells
is also an uncommon finding. Out of these cardiac tumors, contribution of Cardiac
Myeloid Sarcoma (CMS) is even more smaller thereby limiting our knowledge about
this rare entity. Because of its very lower incidence, an exact guideline for
diagnosis and management is still missing and usually haematologists around the
world are treating CMS based on their clinical acumen. Aim of this review is to
briefly discuss the presenting clinical feature, differential diagnosis,
diagnostic workup and management based on published articles related to CMS till
date.
PMID- 28511493
TI - Isolated Central Nervous System (CNS) Relapse in Paediatric Acute Promyelocytic
Leukaemia: A Systematic Review.
AB - INTRODUCTION: Extramedullary disease, as a whole, is rare in Acute Promyelocytic
Leukaemia (APML). If at all relapse occurs, following sites are involved: Central
Nervous System (CNS), skin, testes, mediastinum, gingiva, and ear. Isolated CNS
relapses after complete morphological and molecular remission is rarer
particularly in children. AIM: To review the literature systematically to find
out the incidence of isolated CNS relapse in paediatric APML cases. MATERIALS AND
METHODS: A systematic search of major databases (Medline, Pubmed and Google
Scholar) was conducted. We included all types of studies that reported about
incidence or prevalence of isolated CNS relapse in children upto 18 years of age
with APML. RESULTS: A total of nine studies (with 10 cases of isolated CNS
relapse) were included. Majority (70%) was high risk patients, and 60% were <=six
year-old. Nearly, 50% were having the mean time to relapse <12 months and most
(60%) of them were male. The children who died were having shorter time to CNS
relapse (around 12 months), and were older (>6 to 18 years). CONCLUSION: In the
present review, disease in the high-risk group, male sex, younger age (<=six
years-old), and Promyelocytic Leukaemia/Retinoic Acid Receptor Alpha (PML-RARA)
detection was found to be associated with isolated CNS relapse in children with
APML. Cerebrospinal fluid (CSF) examination along with immunophenotyping and
Reverse Transcription polymerase Chain Reaction (RT-PCR) for PML-RARA is required
for a definite diagnosis and early treatment of patients to improve overall
survival.
PMID- 28511494
TI - Eyelid Malignancies- Always Quite Challenging.
AB - The diagnosis and management of eyelid cancers are quite challenging. Eyelid
tumours are relatively rare diverse group of diseases varied in their
presentation and extent. Many benign tumours and inflammatory conditions quite
frequently masquerade eyelid cancers. Eyelid cancers are not single entity but
comprise a wide range of tumours with extremes of tumour biology from indolent to
very aggressive histopathologic types. Compromise on aesthetics and eyelids'
indispensable function of protecting the eyes during management, may lead to
untoward cosmetic disfigurement and loss of vision. On the other hand, inadequate
cancer clearance will also be vision threatening and life threatening due to loco
regional recurrence and metastasis. To strike an optimal balance is a challenging
task, to achieve 'cancer cure' with maximum preservation of function and
cosmetics. In addition, the integration of other modalities of treatment,
judicious selection and their sequencing require multidisciplinary discussion and
joint management by different specialists. We are presenting four case scenarios,
we met with in our teaching hospital with reference to literature review to
emphasize that eyelid malignancies are not always simple with respect to
diagnosis and management.
PMID- 28511495
TI - Barriers Encountered by Accredited Social Health Activists (ASHA) in Arthritis
Rehabilitation: A Qualitative Study.
AB - INTRODUCTION: Healthy behaviour through education of individuals with arthritis
is the mainstay of long term management. Time and access constraints restrict
medical professionals from active involvement in arthritis education in the
community. Reaching the community through the Accredited Social Health Activists
(ASHAs) is the plan of action operational in India. Hence, the factors
encountered by ASHAs while delivering arthritis education programs need to be
studied. AIM: The aim of the study was to explore the experiences of ASHAs while
delivering arthritis education program. MATERIALS AND METHODS: Qualitative
exploratory design employing semi-structured interviews was adapted for the
study. The interviews were conducted using focus groups of ASHAs from two
geographically similar villages. Inductive analysis of focus group discussions
was undertaken to determine themes, categories and codes. RESULTS: Three broad
themes were identified from the interviews which influenced the performance of
ASHAs. Categories identified show the influence of training, characteristics of
ASHAs, geographical features, family characteristics and community attitude. Few
problems reported were means of transport, time constraints, multiple tasks, type
of incentive and frequency of on-field demonstrations. CONCLUSION: Providing
motivation for altruistic services has always been a challenge to governing
bodies. The issues identified in this study can be addressed prior to integrating
ASHAs for rehabilitation services.
PMID- 28511496
TI - Effect of Passive, Active and Combined Warm up on Lower Limb Muscle Performance
and Dynamic Stability in Recreational Sports Players.
AB - INTRODUCTION: Warm up is an activity that is done before a sports activity. The
warm up can be done actively and passively. The preferred mode is active warm up
in athletes. There are inconclusive effects of passive warm up compared with an
active warm up on short term muscle performance. The cumulative effect of passive
and active warm up on muscle performance and dynamic stability is not known. AIM:
To find out the effects of passive, active and combined warm up on lower limb
muscle performance and dynamic stability in recreational sports players.
MATERIALS AND METHODS: A randomized crossover study was done on 19 recreational
lower limb dominant sports players. Three different warm ups were included in the
study passive, active and combined. Active warm up included series of activities
like cycling, leg press, jump squats, squat jumps while passive warm up included
application of moist heat for a period of 20 minutes on lower limb muscles.
Combined warm up included both passive and active warm up. Six different
sequences were made from these three warm ups. Subjects were screened and
allotted into different groups based on the six warm up sequences after sequence
randomization with 48 hours wash out period. After every warm up session Vertical
Jump Test (VJT) and Star Excursion Balance Test (SEBT) was performed and results
were recorded. Study duration was one year and six months. RESULTS: There was no
difference noticed in both the outcome measures. Mean and SD values for passive,
active and combined warm up are 47.62+/-9.64, 48.50+/-10.16 and 48.87+/-10.70
respectively in Vertical Jump Test (VJT) and 85.43+/-8.61, 85.17+/-8.60 and
85.17+/-8.38 respectively for SEBT. The p-value for mean difference between
passive-active, active-combined, combined-passive are 0.67, 1.00, 0.51
respectively, for VJT and 1.00, 1.00, 1.00 respectively for SEBT. CONCLUSION: All
warm ups are equally effective in short term sports performance.
PMID- 28511497
TI - Assessment of Oxidant-Antioxidant Status and Stress Factor in Recurrent Aphthous
Stomatitis Patients: Case Control Study.
AB - INTRODUCTION: Despite its vast occurrence, the aetiology of Recurrent Aphthous
Stomatitis (RAS) still remains unknown and its aetiology is multifactorial. The
factors believed to be associated with the aetiology of RAS, may disturb the
equilibrium of oxidant-antioxidant status of the organism and may accelerate the
formation of free radicals, resulting in Oxidative Stress (OS). Psychological
stress is believed to act as a triggering factor or modifying factor for RAS.
AIM: To find whether oxidant-antioxidant status and psychosocial stress play a
role in the pathogenesis of RAS. MATERIALS AND METHODS: The study was conducted
on 60 subjects over a period of one year (August 2014-August 2015) equally
divided into two groups-patients with RAS and healthy controls. Psychosocial
stress was analyzed by using Recent Life Changes Questionnaire (RLCQ). Saliva was
analyzed to evaluate Superoxide Dismutase (SOD) and Glutathione Peroxidase
(GSHPx) activities, Malondialdehyde (MDA) and Uric Acid (UA) levels in both the
study and the control groups, using UV spectrophotometry. RESULTS: The mean value
of salivary SOD and MDA was increased while the activity of GSHPx and UA
decreased in the study group when compared to the controls; the difference being
statistically significant (p<0.005). The mean RLCQ stress score was also found to
be increased in the RAS group, which showed elevated levels of mental stresses
when compared to physical stresses. No significant association was observed
between SOD, MDA, GSHPx and UA with high levels of stress score (p>0.05). In the
study group, no correlation was observed between the study variables and gender,
the number of ulcer episodes in one year, the number of ulcers per episode or the
duration of ulcers. CONCLUSION: This study shows that salivary antioxidant levels
show a significant difference in response to OS in RAS patients. An increase in
levels of psychosocial stress is seen associated with patients with RAS
indicating its role as a modifying or triggering factor in the initiation of RAS.
PMID- 28511498
TI - Antioxidant-Oxidant Index as a Biomarker in Oral Potentially Malignant Disorders
and Oral Squamous Cell Carcinoma: A Biochemical Study.
AB - INTRODUCTION: Oxidative stress has been implicated in tumourigenesis by affecting
the actions of various protein kinases and transcription factors, and resulting
in damage to DNA structure by the deamination of nucleotides and the generation
of free radicals. Derangements in the antioxidant defence mechanism have been
considered in the pathogenesis of oral cancer. AIM: To evaluate and compare the
serum levels of nitric oxide and vitamin C in cases of Oral Potentially Malignant
Disorders (OPMDs) and Oral Squamous Cell Carcinoma (OSCC) and healthy controls.
MATERIALS AND METHODS: Serum from 20 patients with OSCC, 20 patients with OPMDs
and 10 healthy subjects were analyzed for levels of nitric oxide and vitamin C
using UV spectrophotometry. Antioxidant-Oxidant Index (AOI) was calculated by
calculating the ratio between the levels of nitric oxide and vitamin C. RESULTS:
The mean nitric oxide levels were elevated in OSCC group, as compared to OPMD and
control group, whereas, mean serum vitamin C levels were reduced in OSCC group as
compared to OPMDs and control group (statistically significant, p<0.05). There
was significant increase in AOI from control group (0.023), OPMDs (0.167) and
OSCC group (0.279) (p<0.05). CONCLUSION: Assessment of levels of antioxidant
oxidant markers are useful tools in monitoring the progression of OPMDs to OSCC.
AOI is an objective tool to assess the oxidative stress in these patients.
PMID- 28511499
TI - Postoperative Pain and Flare-Ups: Comparison of Incidence Between Single and
Multiple Visit Pulpectomy in Primary Molars.
AB - INTRODUCTION: Endodontic treatment performed in either single- or multiple visit
can be followed by numerous short- and long term complications. One of the short
term complications include postoperative pain and flare-ups. The ability to
predict its prevalence and forewarn the patient may go some way towards enabling
coping strategies and help dentist in pain management treatment decisions. AIM:
To compare the incidence and intensity of postoperative pain and flare-ups
between single- and multiple visit pulpectomy in primary molars. Also, to
correlate the preoperative status of the pulp to postoperative pain and flare
ups. MATERIALS AND METHODS: Eighty primary molars indicated for pulpectomy were
included in the study and divided into two groups. Tooth treated and preoperative
status of the pulp vitality was recorded. All the conventional steps in
pulpectomy were followed. Teeth in Group 1 (single visit pulpectomy) were
obturated on the same visit. Teeth in Group 2 (multiple visit pulpectomy) were
obturated in the subsequent appointment. The recording of postoperative pain,
flare-ups, use of medication were done after 24 hours, seven days and one month.
RESULTS: Four cases in both the groups reported postoperative pain (10%) at 24
hour recall, p=0.74. One flare-up (2.5%) was recorded in each group p=0.67. None
of the patients reported pain at seventh day and one month recall. Postoperative
pain was recorded in five non-vital teeth (13.5%) and three vital teeth (6.9%).
However, it was statistically not significant p=0.53. CONCLUSION: From the
perspective of our study there was a low incidence of postoperative pain. The
majority of patients in both groups reported no pain or only minimal pain within
24 hours of treatment. There were no differences between single- and multi visit
treatment protocols with respect to the incidence of postoperative pain. No
significant correlation could be found between pulp vitality and the incidence of
postoperative pain.
PMID- 28511500
TI - Comparative Evaluation of the Efficacy of Probiotic, Herbal and Chlorhexidine
Mouthwash on Gingival Health: A Randomized Clinical Trial.
AB - INTRODUCTION: Due to inherent limitations of Chlorhexidine (CHX), search for an
effective and potentially safe anti-plaque agent has led to emergence of
alternative products. AIM: The present study evaluated the comparative efficacy
of probiotic, herbal and CHX mouthwashes on gingival health of healthy
individuals. MATERIALS AND METHODS: The present study was randomized parallel
group controlled trial. A group of 45 healthy subjects in the age group of 18-21
years received complete supragingival scaling at baseline and study variables
viz., Oral Hygiene Index - Simplified (OHI-S), Plaque Index (PI) and Gingival
Index (GI) were recorded. Subjects were then randomly divided into three groups
(15 in each group) and were randomly intervened with three different mouthwashes
i.e., HiOra mouthwash, CHX mouthwash and Probiotic mouthwash. Variables were
again recorded on the seventh and 14th day after use of mouthwashes and data
obtained was subjected to statistical analysis. RESULTS: There was no significant
difference in the efficacy of CHX, HiOra regular and probiotic mouthwashes on
plaque accumulation, gingival health and oral hygiene status. CONCLUSION: Herbal
and probiotic mouthwashes can prove to be effective alternatives to CHX with
minimal side effects.
PMID- 28511501
TI - Gamma Glutamyl Transpeptidase, Smokeless Tobacco, Chronic Periodontitis:
Exploring the Link.
AB - INTRODUCTION: Oxidative Stress (OS) is implicated in the pathogenesis of many
systemic and oral diseases such as periodontal disease. Smokeless tobacco extract
produces apoptosis and causes an imbalance between reactive oxygen species and
antioxidants, such as Gamma Glutamyl Transpeptidase (GGT). Epidemiological
research implied serum GGT within its normal range to be an early sensitive
enzyme related to OS. AIM: To assess how GGT fares as a biomarker in
periodontitis subjects with or without the usage of smokeless tobacco and
correlate it with clinical parameters. MATERIALS AND METHODS: Ninety subjects
were divided into three groups of healthy, chronic periodontitis, and smokeless
tobacco users with chronic periodontitis from the dental outpatient department of
P.M. Nadagouda Memorial Dental College and Hospital. Serum samples of patients
were collected after obtaining consent and analyzed for GGT. Statistical Analysis
was performed using ANOVA, and Pearson's correlation coefficient. RESULTS: GGT
levels were found to be significantly higher in chronic periodontitis patients
compared to smokeless tobacco users with chronic periodontitis and healthy
subjects. Conclusion: GGT may be used as a quick, easy and precise marker for
measuring OS in patients with chronic periodontitis and smokeless tobacco users.
PMID- 28511502
TI - Comparative Evaluation of Three Herbal Solutions on the Disinfection of
Guttapercha Cones: An In vitro Study.
AB - INTRODUCTION: Guttapercha (GP) cones are usually supplied in aseptic, sealed
packages from the manufacturers, but once exposed to the dental office
environment or even by handling; they can be contaminated by a number of
microorganisms. Supplementary decontamination of GP cones is critical. As they
cannot be sterilized by moist or dry heat, cold sterilization, using
disinfectants should be used. AIM: The aim of the study was to evaluate rapid,
reliable, convenient and effective method of disinfection of GP cones using
readily available herbal solutions such as Aloevera Juice, Amla Juice and Pancha
Tulsi. MATERIALS AND METHODS: Ninety GP cones were selected for the study. Based
on the contaminants used, 80 GP cones were divided into two groups: Group A and
Group B with 40 cones in each group and the remaining 10 cones which were
uncontaminated served as negative control. The cones from Group A were
contaminated with Staphylococcus aureus (S. aureus) and Group B were contaminated
with Enterococcus faecalis (E. faecalis). The contaminated cones from both groups
were subdivided into four groups with 10 cones in each group. Group I cones were
disinfected with Aloevera Juice, Group II with Amla Juice and Group III with
Pancha Tulsi. The fourth group consisted of GP cones without any disinfection
which served as positive control. All the cones were then incubated in
thioglycollate media for seven days. The thioglycollate media was subcultured and
colony forming units were counted. The data were analyzed by one way ANOVA
(analysis of variance) and Post-hoc Tukey test using SPSS 17.0 software. RESULTS:
Mean colony forming units were compared in all the groups and there was a
statistically significant difference present among the groups (p<0.01). Pancha
Tulsi was found to be most effective disinfectant followed by Amla Juice.
CONCLUSION: All the herbal solutions were found to be effective in the
disinfection of GP points. However, Pancha Tulsi possesses superior antibacterial
activity when compared with Aloevera Juice and Amla juice.
PMID- 28511503
TI - Evaluation of Total and Lipid Bound Sialic Acid in Serum in Oral Leukoplakia.
AB - INTRODUCTION: Oral cancer has become the most common cause of cancer related
mortality which may be preceded by oral potentially malignant disorders. Altered
glycosylation of glycoconjugates, such as sialic acid are one of the most
important molecular changes accompanied during malignant transformation in
precancerous lesions like Oral Leukoplakia (OL), and correlating them
histopathologically with grades of epithelial dysplasia which will serve clinical
significance. AIM: The aim of this study was to evaluate the significance of
serum Total Sialic Acid (TSA) and serum Lipid Bound Sialic Acid (LSA) as a
prognostic serum marker in Oral Leukoplakia. MATERIALS AND METHODS: Blood samples
were collected from 30 patients diagnosed with OL and 30 healthy controls. Serum
sialic acid (total and lipid bound) levels were measured using spectrophotometer.
Tissue samples were histopathologically typed and were graded for epithelial
dysplasia. Data were analysed using Independent t-test and Kruskal Wallis method.
RESULTS: Serum levels of both total and lipid bound sialic acids were found to be
increased in OL when compared to healthy controls. The mean TSA levels among
those in the OL group (45.3+/-4.2) were significantly greater than healthy
controls (29+/-2.2). On multiple comparison the highest mean TSA level was found
in severe OL compared to moderate and mild OL (p<0.05). The mean levels of LSA
were found to be statistically non-significant between the groups. CONCLUSION:
The present study showed that the serum levels of both TSA and LSA were found to
be increased in OL when compared to apparently healthy controls. We also found
that with increasing grades of epithelial dysplasia TSA levels were found to be
gradually increasing which was significant for this study serving as an early
indicator for the detection of malignant transformation in OL.
PMID- 28511504
TI - Prevalence of Distal Caries in Mandibular Second Molar Due to Impacted Third
Molar.
AB - INTRODUCTION: A tooth is said to be impacted if it does not reach the occlusal
plane even after two-thirds root formation. The aetiology of impacted teeth is
varied and multi-factorial. Significant problems associated with impacted teeth
include trismus, infection, cervical caries of second molars. AIM: This study was
aimed to assess the prevalence of distal caries in second molar teeth due to
impacted third molars and to compare with similar studies conducted elsewhere.
MATERIALS AND METHODS: Study included assessment of patients reporting between
2009 to 2014 for dental care at College of Dentistry, King Khalid University,
Abha, Kingdom of Saudi Arabia. This is a retrospective cross-sectional study
which included a total of 6000 Orthopantomograms (OPGs). The data collected was
decoded and entered into excel spread sheet. Descriptive analysis of the data was
done and results were displayed as frequency table and graphs. RESULTS: A total
of 979 patients had impacted third molars (16.31%). A total of 39% patient's with
impacted third molars had distal cervical caries in second molar. Mesioangular
impaction was the most prominent type. This was closely followed by horizontal
impaction causing distal caries in second molars. Age group between 21-28 years
and male gender had the higher prevalence of distal caries in second molar teeth
due to impacted third molars. CONCLUSION: A total of 39% of the patients with
impacted mandibular third molars had distal cervical caries in second molars.
Mesioangular type, male gender, age group 21-28 years were the prominent factors
associated with distal caries in second molar teeth due to impacted third molars.
PMID- 28511505
TI - Effectiveness of Chewable Tooth Brush in Children-A Prospective Clinical Study.
AB - INTRODUCTION: Dental plaque is one of the aetiological factors in causation of
dental caries. Effective removal of plaque can reduce the incidence of caries.
Various agents for removing plaque has been introduced, of which, chewable brush
is a recent advance. There is limited evidence assessing the effectiveness of
using chewable brush in children. AIM: The aim of this study was to evaluate the
effectiveness of chewable brush in relation to efficiency in plaque removal and
reduction in S.mutans counts in saliva. MATERIALS AND METHODS: Ten children of
six-nine years with their first molars erupted were included in the study and the
children were supervised for their normal brushing for 7 days. The baseline Oral
Hygiene Index-Simplified (OHI-S), Plaque Index (PI) and Decay, Missing Filled
Tooth Index (DMFT-I) were noted and the saliva sample was collected from the
children. The sample was sent for microbiological examination of S.mutans count
and the pH of the saliva was also determined. The children were advised to brush
their teeth twice daily for seven days using chewable brush. On the seventh day,
the indices were noted again and the saliva sample was collected and sent for
microbiological examination. Statistical analysis was done using paired t-test to
compare the pre and post-brushing index scores, S. mutans count and salivary pH.
RESULTS: There was a significant reduction in the debris index (p<0.001), oral
hygiene index (p<0.000), plaque index (p<0.001), pH of the saliva (p<0.037) and
S. mutans level (p<0.006) before and after brushing with chewable brush. However,
the calculus index remained unchanged (p=0.168). CONCLUSION: Chewable brush can
be used as an effective alternative to manual brushing in children.
PMID- 28511506
TI - An Assessment of Correlation between Dermatoglyphic Patterns and Sagittal
Skeletal Discrepancies.
AB - INTRODUCTION: Investigators over years have been fascinated by dermatoglyphic
patterns which has led to the development of dermatoglyphics as a science with
numerous applications in various fields other than being the best and most widely
used method for personal identification. AIM: To assess the correlation between
dermatoglyphic patterns and sagittal skeletal discrepancies. MATERIALS AND
METHODS: A total of 180 patients, aged 18-40 years, were selected from those who
attended the outpatient clinic of the Deparment of Orthodontics and Dentofacial
Orthopedics, Mar Baselios Dental College, Kothamangalam, Kerala, India. The
fingerprints of both hands were taken by ink and stamp method after proper hand
washing. The patterns of arches, loops and whorls in fingerprints were assessed.
The total ridge count was also evaluated. Data was also sent to the fingerprint
experts for expert evaluation. The sagittal jaw relation was determined from the
patient's lateral cephalogram. The collected data was then statistically analyzed
using Chi-square tests, ANOVA and Post-hoc tests and a Multinomial regression
prediction was also done. RESULTS: A significant association was observed between
the dermatoglyphic pattern exhibited by eight fingers and the sagittal skeletal
discrepancies (p<0.05). An increased distribution of whorl pattern was observed
in the skeletal Class II with maxillary excess group and skeletal Class II with
mandibular deficiency group while an increased distribution of loop pattern was
seen in the skeletal Class III with mandibular excess group and skeletal Class
III with maxillary deficiency group. Higher mean of total ridge count was also
seen in the groups of skeletal Class II with maxillary excess and skeletal Class
II with mandibular deficiency. Multinomial regression predicting skeletal pattern
with respect to the fingerprint pattern showed that the left thumb impression
fits the best model for predicting the skeletal pattern. CONCLUSION: There was a
significant association between dermatoglyphic patterns and sagittal skeletal
discrepancies. Dermatoglyphics could serve as a cost effective screening tool of
these craniofacial problems.
PMID- 28511507
TI - Evaluation of C-Reactive Protein and Fibrinogen in Patients with Chronic and
Aggressive Periodontitis: A Clinico-Biochemical Study.
AB - INTRODUCTION: Periodontal disease is characterised by chronic infection and
inflammation in periodontal tissues leading to destruction of alveolar bone with
subsequent tooth loss. Periodontal infections are the result of an interaction
between tooth associated microbial biofilms and the host defences. Periodontal
pathogens can affect local and systemic immune and inflammatory responses. AIM:
The aim of the present study was to evaluate serum C-Reactive Protein (CRP),
plasma fibrinogen and peripheral blood levels in healthy subjects, chronic and
aggressive periodontitis patients. MATERIALS AND METHODS: A total of 55 subjects,
27 males and 28 females were selected for the study. Blood samples were taken
from healthy controls (n=20) and patients with chronic periodontitis (n=20) and
aggressive periodontitis (n=15). The periodontal status of each patient was
assessed by recording Oral Hygiene Index-Simplified (OHI-S), Bleeding Index (BI),
Probing Pocket Depth (PPD) and Clinical Attachment Level (CAL). The levels of
serum CRP were measured using high sensitivity Enzyme Linked Immunosorbent Assay
(ELISA) and levels of plasma fibrinogen were measured using Quantitative
Immunoturbidimetric assay. Data description was done in the form of mean and
standard deviation and analysis of data was done using one way ANOVA (Analysis of
Variance) and Students t-test to test the statistical significance between
groups. RESULTS: The levels of serum CRP and plasma fibrinogen was increased in
patients with chronic and aggressive periodontitis when compared to healthy
controls (p<0.001). A positive correlation was found to exist between levels of
clinical parameters like OHI-S, BI, PPD and CAL when compared with CRP and
fibrinogen as well as with the study groups. CONCLUSION: The finding of the
present study suggests the role of serum as a diagnostic marker in inflammatory
conditions and indicates that levels of CRP and fibrinogen may serve as important
biomarkers for evaluating the association between periodontitis and
cardiovascular diseases.
PMID- 28511509
TI - Comparative Evaluation of Colour Stability and Surface Hardness of Methacrylate
Based Flowable and Packable Composite -In vitro Study.
AB - INTRODUCTION: With the advent of new technology in material sciences in recent
years, the quality of composite resin restorations has improved; however,
discolouration and wear of composite resin materials remains to be a major
problem in long-term clinical studies. AIM: The aim of the present study was to
compare the colour stability and surface hardness of methacrylate based flowable
nano composite with methacrylate based packable nano composite. MATERIALS AND
METHODS: The difference in colour stability and microhardness of the three
composites: G aenial Universal Flo (GC India), Filtek Z350XT (3MESPE) and Tetric
N Ceram (Ivoclar Vivadent) were evaluated. Forty eight disc shaped specimens were
made out of three different resin composite materials which were subdivided into
two groups of Colour Stability (CS) and Vicker's Hardness (VH). For colour
stability, specimens were immersed in staining solution consisting instant coffee
for 72 hours, and then specimens were rinsed thoroughly under tap water and
subjected to 10 strokes of brushing with a soft-grade toothbrush. The colour
measurements were obtained using spectrophotometer and the process was repeated
every 72 hours for three weeks. VH was evaluated using microhardness tester
(Zwick/Roell Vicker's Microhardness Tester). Vicker's Hardness Numbers (VHN) were
determined from indentations made under 10 N load for 15 seconds by the
arithmetic mean of three indentation values randomly performed. One-way ANOVA and
Tukey's post-hoc analysis were applied. RESULTS: Statistically significant
difference was found in comparison of colour stability at different time interval
in study groups (p<0.001). Filtek Z350XT group showed least discolouration
followed by Tetric N Ceram group and highest colour change in G aenial Universal
Flo group after immersion for 21 days. Mean microhardness value of Filtek Z350XT
(101.62) group was found to be significantly different from Tetric N Ceram group
(63.74) (p<0.001*) and G aenial Universal Flo group (56.75) (p<0.001*).
CONCLUSION: Greatest CS and VH was seen in Filtek Z350XT followed by Tetric N
Ceram and least values were seen in G aenial Universal Flo.
PMID- 28511510
TI - Patterns of Partial Edentulism and its Relation to Khat Chewing in Jazan
Population - A Survey Study.
AB - INTRODUCTION: Partial edentulism is a prime indicator of overall oral health in a
given country. Khat chewing habit in the south region of Saudi Arabia is widely
practiced by a majority of the population. AIM: To determine the frequency of
Kennedy's classes in each arch among different age groups, gender and to find out
the relationship between khat chewing and the pattern of partial edentulism.
MATERIALS AND METHODS: The data was collected from 780 subjects reporting to the
College of Dentistry, Jazan University, who required removable partial dentures.
Clinical intra-oral and radiographic examinations were done. The study subjects
were divided into five age groups, 20-29, 30-39, 40-49, 50-59 and >= 60 years
respectively. Khat chewing hours/day and type of Kennedy's classes were recorded.
The data were entered into a Statistical Package for Social Sciences program and
analysed accordingly using Fisher-Exact test. RESULTS: Class III was the highest
in all middle age groups followed by Class I. Class III was the highest in males,
while in females, Class I was the highest in both arches. Class IV was the lowest
in all age groups, both arches, and genders. Among khat chewers Class III was the
highest followed by class I in both arches. Class IV was the highest in >12 hours
duration in maxilla but in the mandible, Class I and II were the highest in 1-6
hours duration. The obtained p-values were statistically significant (p<0.001) in
all tested variables and age groups. CONCLUSION: Kennedy's Class III was the
highest followed by Class I, while Kennedy's Class IV was the lowest in all age
groups and both arches regardless of khat chewing durations. In males Class III,
was the highest, while in females Class I was the highest in both arches.
PMID- 28511508
TI - A Randomized Placebo- Controlled Double Blind Clinical Trial of Quercetin in the
Prevention and Treatment of Chemotherapy-Induced Oral Mucositis.
AB - INTRODUCTION: Oral Mucositis (OM) is a serious complication of chemotherapy that
results in painful debilitating inflammation that sometimes ends in interruption
of treatment. AIM: The study evaluated the effect of quercetin (a natural
flavonoid) on preventing and treating chemotherapy induced OM in patients with
blood malignancies. Materials and Methods: This double-blind, placebo controlled
randomized trial was carried out on 20 adult patients who underwent high dose
chemotherapy for blood malignancies. Patients were divided into two groups (10
patients in the intervention group and 10 patients in the control group).
Patients in the intervention group were administered 250 mg quercetin capsules
twice daily for four weeks. RESULTS: Nine out of 20 patients developed OM (three
in the intervention group and six in the control group). The incidence of OM was
lower in the intervention group although it was not statistically significant
(p=0.189). The mean severity of OM was higher in the intervention group (2.6 vs
2). Healing time, age, gender, type of malignancy, drug type and duration of OM
were not different in two groups. CONCLUSION: The incidence of mucositis was
lower in the quercetin group, but mucositis was more severe in the intervention
group, which may be due to lower oral health status in the intervention group.
PMID- 28511511
TI - Health-Related Quality of Life of Persons after Rhinoplasty: A Longitudinal Study
among Iranian Population.
AB - INTRODUCTION: Despite the growing number of cosmetic rhinoplasty surgeries in
Iran in recent years, there is little information about the effects of this
procedure on the subjects' Quality of Life (QoL). This study examined the QoL
after rhinoplasty in subjects without nasal obstruction, who wanted the surgery
for aesthetic reasons, three and six months postoperatively. AIM: The aim of this
study was to assess the changes of QoL in clients who take rhinoplasty. MATERIALS
AND METHODS: This was a prospective study conducted in Tehran, Iran. Using
convenience sampling, 150 subjects who had undergone cosmetic rhinoplasty from
June 2013 to June 2014 were invited to participate in the study. Patients' QoL
was measured one week before and three and six months after rhinoplasty, using
the Iranian version of the 36-item Short Form (SF-36) questionnaire. Descriptive
statistics, Pearson correlation coefficient, one-way ANOVA, paired t-test, and
independent sample t-test were used for data analysis. RESULTS: Most of the
participants were women (64%), and the mean age was 26.8+/-5.4 years (range: 18
41 years). The mean QoL scores before and three and six months after rhinoplasty
were 67.26+/-26.01, 68.00+/-15.7 and 83.65+/-9.6, respectively. None of the
measured demographic characteristics showed any correlation or relationship with
the participants' QoL before and after the procedure (p>0.05). CONCLUSION: QoL
can be considered as a quality indicator of health care systems. This study shows
that the persons' QoL improved six months after cosmetic rhinoplasty.
PMID- 28511513
TI - Sexual Dimorphism of Maxillary Sinus: A Morphometric Analysis using Cone Beam
Computed Tomography.
AB - INTRODUCTION: Age and sex determination in forensic sciences are primary
components of any skeletal analysis. As most bones used for sex determination are
recovered in incomplete state, it is often necessary to use bones that are
recovered intact e.g., the maxillary sinus. Cone Beam Computed Tomography (CBCT)
can provide precise information about complex anatomical structures, as it is
characterized by rapid volumetric image acquisition with high resolution. AIM:
The present study was designed to evaluate the size and volume of Maxillary Sinus
(MS) in determining gender by CBCT. MATERIALS AND METHODS: Bilateral maxillary
sinus images (left and right) were acquired for 100 patients (50 females and 50
males) and different parameters (width, length, height, area, perimeter and
volume) were measured and evaluated. Mean and standard deviation of both
maxillary sinuses measurements were calculated and compared. The data was
subjected to discriminative statistical analysis and analysed using unpaired t
test. RESULTS: Comparison between male and female groups showed statistically
insignificant differences on both the right and left sides with respect to the
maxillary sinus length, height, area, volume and perimeter. However, the female
group showed statistically significant higher values for left side MS width
(p=0.041) and left side MS width can be used to determine gender with an overall
accuracy of 60%. The final result of discriminative analysis shows that the
ability of the maxillary sinus to identify gender was 68% in males and 74% in
females with an overall accuracy of 71%. CONCLUSION: Maxillary sinus width can be
used as an aid in forensic anthropology for gender determination.
PMID- 28511512
TI - Evaluation of Correlation between Salivary Calcium, Alkaline Phosphatase and
Osteoporosis- A Prospective, Comparative and Observational Study.
AB - INTRODUCTION: Fixed and/or removable prosthodontics caters to the restorative
needs of the largest count of geriatric patients whose rehabilitative procedures
depend on the quality and quantity of available bone. The common diagnostic
parameters for quantifying bone may involve an invasive blood examination, an
expensive bone densitometry procedure or a urine analysis. Sialometry involving
the basic biochemistry of saliva analysis may be proposed as an alternative to
the conventional investigative protocol and its usefulness may be attributed
owing to its non invasive and simpler procedure. AIM: The aim of this study was
to compare the salivary calcium and alkaline phosphatase among osteoporotic,
osteopenic and normal edentulous subjects. MATERIALS AND METHODS: A prospective,
comparative and observational study was carried out on 80 selected edentulous
subjects (40 males and 40 females) aged 55-75 years (30 osteoporotic, 30
osteopenic and 20 control). A sample of saliva was taken for the study. Salivary
calcium was measured by Arsenazo reaction; and alkaline phosphatase by the
International Federation of Clinical Chemistry (IFCC) method. Statistical
analysis was done by unpaired t-test. A comparison was made in the levels of
salivary calcium and alkaline phosphatase with that of osteoporosis and
osteopenia. RESULTS: The mean salivary calcium and alkaline phosphatase levels
were found to be significantly higher in the osteoporotic and osteopenic
edentulous subjects as compared to the control group. CONCLUSION: Salivary
calcium and alkaline phosphatase are increased significantly in case of
osteoporosis and osteopenia. Hence, screening of salivary samples of patients may
be an effective indicator for the detection of underlying disorders of bone
metabolism.
PMID- 28511514
TI - Evaluation of Relative Position of Mandibular Foramen in Children as a Reference
for Inferior Alveolar Nerve Block using Orthopantamograph.
AB - INTRODUCTION: The Mandibular Foramen (MF) is a landmark for administering local
anaesthetic solution for Inferior Alveolar Nerve Block (IANB). The position of MF
shows considerable variation among different ethnicity, ages and on either sides
even within the same individual. Failure to achieve IANB leading to repeated
injection of the local anaesthetic solution will not only pose a behaviour
problem in children but can also lead to systemic toxic level of anaesthetic
solution being administered. AIM: To determine the relative position of the
mandibular foramen in 7 to 12-year-old children in relation to the mandibular
occlusal plane and the deepest point on coronoid notch. MATERIALS AND METHODS:
Ninety orthopantamograph of 7 to 12-year-old children were selected from the
database and were divided into three groups: Group 1 (G1): seven to eight-year
old, Group 2 (G2): 9 to 10-year-old and Group 3 (G3): 11 to 12-year-old. The
radiographs were traced on acetate paper, anatomical landmarks were marked and
linear measurements were noted from the Mandibular Lingula (ML) to the occlusal
plane, and to the deepest point on coronoid notch. The data obtained was
tabulated and subjected to statistical analysis. One way ANOVA test followed by
Bonferroni post hoc analysis and Student's paired t-test were used. RESULTS:
Mandibular foramen is approximately, 2-3 mm above the occlusal plane and 11.6
13.0 mm from deepest point of coronoid notch for seven to eight-year-old
children, 3-4 mm above the occlusal plane and 13.0-13.9 mm from deepest point of
coronoid notch for 9-10 year age group and 5.5-6.5 mm above the occlusal plane
and 11.9-12.2 mm from deepest point of coronoid notch for children of the ages 11
12 years. The linear distance from the deepest point of coronoid notch to the
mandibular lingula showed statistical significance in G2 vs G3 on right side G1
vs G2 and G2 vs G3 on the left side. The variance of this distance for either
side showed statistical significance for G1 and G2. CONCLUSION: The distance from
the mandibular lingula to the occlusal plane showed gradual increase in all the
three groups, which was statistically significant. The position of the mandibular
foramen is not bilaterally symmetrically for any of the considered age groups.
PMID- 28511515
TI - Comparative Evaluation of Antibacterial and Adhesive Properties of Chitosan
Modified Glass Ionomer Cement and Conventional Glass Ionomer Cement: an In vitro
Study.
AB - INTRODUCTION: Recent studies have reported the incorporation of modifiers with
conventional Glass Ionomer Cement (GIC) to enhance its antibacterial effect. One
such modification being the addition of Chitosan (CH). However, these modifiers
might affect the physical properties of the restorations. AIM: The aim of the
present study was to investigate the effect of modifying the liquid phase of
conventional GIC with 10% v/v CH on the antibacterial properties and adhesion to
enamel in comparison to conventional GIC. MATERIALS AND METHODS: The liquid of
commercially available restorative GIC (Fuji IX, GC Industrial Corporation,
Japan) was modified with 10% v/v CH solution (Everest Biotech, Bengaluru). GIC
powders were mixed with the unmodified and the CH-modified liquids at the desired
powder/liquid ratio. Fourier Transform Infrared Spectroscopy (FTIR) was used to
determine the setting reaction between the conventional and CH modified GIC
liquid with GIC powder. For evaluation of the antibacterial properties, biofilms
of Streptococcus mutans (S. mutans) were formed on the GIC discs and
characterized by Scanning Electron Microscope (SEM). For the characterization of
the adhesive properties, the unmodified and CH-modified GICs were bonded to the
enamel surface and the microshear bond strength (MUSBs) was evaluated. Student's
paired t-test was used to compare the micro-shear bond strength between CH
modified GIC and unmodified GIC. RESULTS: Modification with 10% v/v CH solution
improved the antibacterial properties of GIC against S. mutans in terms of
resistance to biofilm formation which was assessed using SEM. Microshear bond
strength of CH modified GIC was 85.40 MPa compared to 46.94 MPa of conventional
GIC. This difference was found to be statistically significant. CONCLUSION:
Modifying the liquid phase of a conventional GIC with 10% v/v CH significantly
improves the antibacterial property of GIC as well as its adhesion to enamel.
PMID- 28511516
TI - To Evaluate and Compare Periodontal Disease and Smoking as a Parallel Risk Factor
for Systemic Health by Gauging the Serum C-Reactive Protein Levels.
AB - INTRODUCTION: Physiologic and metabolic changes that occur immediately after a
damage or disease are known as Acute Phase Reaction (APR). Acute Phase Proteins
(APP) are blood proteins secreted by hepatocytes during APR C-Reactive Protein
(CRP) being the important one. AIM: Present study was designed to estimate and
compare the levels of the serum CRP in current smokers, former smokers and non
smokers, with and without periodontitis. MATERIALS AND METHODS: An experimental
study was planned on 165 subjects who were divided into four groups. Group 1-
nonsmokers with periodontitis. Group 2- smokers without periodontitis. Group 3-
smokers with periodontitis. Group 4- former smokers without periodontitis.
Healthy controls were not included in the study as the normal range of CRP in
health is already established. Periodontal examination was done and serum CRP was
measured. After getting the acceptance to be a part of the study, written
informed consent was taken from each participant. Data analysis was done by ANOVA
and post-hoc tests. RESULTS: Highest level of CRP was found in smokers with
periodontitis followed by non-smokers with periodontitis and smokers without
periodontitis. Former smokers had minimum CRP compared to the other groups (p
value=0.03). CONCLUSION: Periodontitis alone and in combination with smoking
increases the systemic inflammatory burden and associated cardiovascular risk.
This fact should be communicated thoroughly to the general population, general
dentist, physicians and cardiovascular specialist to enhance early screening and
multidisciplinary treatment.
PMID- 28511517
TI - Holistic Healing Through Herbs: Effectiveness of Aloe Vera on Post Extraction
Socket Healing.
AB - INTRODUCTION: Advances in the field of alternative medicine has encouraged the
use of various natural products for multiple uses in the field of dentistry for
treatment of various oral diseases. A natural herbal product is Aloe vera, which
has number of benefits with no reported side effects and gaining considerable
importance in clinical research. AIM: The aim of this cross-sectional randomized
interventional study was to evaluate the effectiveness of Aloe vera in the
healing of post extraction sockets. MATERIALS AND METHODS: A sample size of 40
patients undergoing atraumatic extraction was divided into two groups. Group A
patients were prescribed only analgesics and followed for seven consecutive days
and socket healing assessment was done. Group B-Patients were given Aloe vera
soaked gel foams, followed up to the third and seventh day by two observers and
the socket healing was assessed using the standardized index by Landry, Turnbull
and Howley. In addition to healing the common complaint associated with
extraction wound, the pain was assessed using numerical rating scale. Data
obtained was statistically analysed using Mann-whitney U test, Wilcoxon Signed
ranks test and Spearman's rank correlation method. RESULTS: Control group on the
third and the seventh day showed healing of 60% and 70% respectively and the Aloe
vera group showed a better result having a healing potential of 70% on the third
day and 90% on the seventh day which was statistically significant with a (p
value<0.001). Aloe vera group showed a significant decrease in pain after two
hours on the day of extraction followed by second, third and seventh day which
was statistically significant (p-value<0.001) and better than the control group.
CONCLUSION: Aloe vera has been proved to have a unique property that is
implicated in better healing than other group without any side effects. Aloe vera
is economical, effective, powerful nutritional supplement and antioxidant that
protects and promotes wound healing.
PMID- 28511518
TI - Fat Free Pleomorphic Lipoma of Oral Cavity: A Rare Entity.
AB - Pleomorphic lipoma is a rare, benign, soft tissue neoplasm that
characteristically occurs as a subcutaneous mass in the posterior neck or upper
back and rarely in the tonsillar fossa and oral cavity. Histologically,
pleomorphic lipoma contains varying amounts of mature fat, areas of spindle and
pleomorphic cells, floret giant cells and thick rope - like collagen in a myxoid
stroma. Pleomorphic lipoma with scanty fatty elements is called the fat free
variant of pleomorphic lipoma. The combination of meagre amount of fat and
presence of pleomorphic elements gives a pseudosarcomatous picture under the
microscope leading to misdiagnosis and over treatment. Here, we report a case of
fat free pleomorphic lipoma, first of its kind in the oral cavity and discuss the
diagnostic features and differential diagnosis.
PMID- 28511519
TI - A Giant Cutaneous Horn Projecting from Verrucous Carcinoma of Buccal Mucosa: A
Rare Case Report.
AB - Cutaneous horn is conical shape of compact keratin that resembles a miniature
animal horn. Though morphologically similar to horns in animals they are
histologically very different from them. It is a circumscribed, conical,
hyperkeratotic dense protrusion with epithelial cornification above the skin
surface in response to a wide range of underlying benign and malignant
pathological changes. Though benign, a cutaneous horn holds the potential to be
premalignant or malignant. In India till now six cases has been reported with
cutaneous horn at various unusual sites. We report a unique case of 52-year-old
woman with a giant cutaneous horn at left oral commissure with underlying
verrucous carcinoma of left buccal mucosa which is a very rare location for such
lesion. Considering its malignant potential, adequate therapy requires wide
excision with a tumour-free margin of at least 1 cm, particularly in the facial
region where the incidence of malignancy is higher.
PMID- 28511520
TI - Effect of Trauma to Primary Tooth on Permanent Maxillary Incisors: A Clinical
Case Report.
AB - Trauma to primary tooth leads to abnormal variations in crown and root canals of
permanent teeth that presents a challenge in diagnosis and clinical management to
the practitioner. This article presents a detailed case report of the endodontic
treatment of a three canalled maxillary central incisor and maxillary lateral
incisor having single canal with open apex linked with periodontal defect. Root
canals were prepared with hand files and canals were irrigated with 2.5% sodium
hypochlorite solution. Calcium hydroxide was placed as an intracanal medicament.
As the expected healing did not occur even after one month of calcium hydroxide
therapy, so periapical endodontic surgery was performed using Platelet Rich
Plasma (PRP). Satisfactory clinical and radiographic results were obtained at 12
months. Detailed knowledge of the anatomical variations in the root canal and
awareness of their configuration is essential for the success of such cases.
PMID- 28511521
TI - Cu-sil Denture- A Space Maintainer for Function- In Paediatric Patients.
AB - The purpose of this report is to introduce Cu-sil like denture as a functional
space maintainer. Here, we report two paediatric cases treated with Cu-sil like
denture with multiple edentulous spaces and partially erupted/compromised
permanent teeth. Cu-sil like denture not only serves as removable partial
functional space maintainer, but also restores the vertical dimension of
occlusion, mastication and aesthetics in children. Cu-sil like denture is used in
elderly patients who are not willing for extraction of remaining few healthy
teeth in the oral cavity. This concept utilizes the remaining natural teeth in
the arch, accommodates them within the denture through perforations made in the
denture base. The gap between the denture base and the tooth is sealed using a
resilient liner. Such denture is used for the paediatric age group in this report
for functional rehabilitation temporarily. The report describes the pros and cons
of the Cu-sil like denture use in children with technique of preparation along
with review of literature.
PMID- 28511522
TI - Iris Positioning Using a Grid Attached to a Spring Bow for a Custom Ocular
Prosthesis.
AB - Eyes are among the first features of the face to be noticed. Loss of an eye due
to congenital, traumatic or pathologic aetiologies causes disfigurement and loss
of sensory feedback. It leaves a psychological impact on the patient, thus
prosthesis should be provided at the earliest to raise the spirits of the
afflicted. Iris positioning is one of the important steps in fabricating
customized ocular prosthesis. In facial asymmetry cases, comparison of both
irises together can be a major disadvantage. This case report illustrates the use
of a unique customized frame spring bow assembly to position the iris disk using
the established parallelism between inter pupillary line to the horizontal plane.
PMID- 28511523
TI - Achondroplasia with Polydactyly: A Case Report.
AB - An eight-year-old girl child reported to the Department of Oral Medicine and
Radiology with the chief complaint of unerupted permanent teeth for past two
years. The child presented features like disproportionately short stature,
rhizomelic shortening of arms and legs, long face, frontal bossing and saddle
nose. Based on the findings of chest and spine radiographs and ultrasound the
case was diagnosed as a rare bone disorder "Achondroplasia". This case also
presents a unique feature of polydactyly. Polydactyly is a manifestation in
clinical medicine because it can serve as an indicator for a plethora of
congenital anamolies. This case gained dental interest because of its
characteristic craniofacial features. This article highlights the peculiar
manifestations of this anamoly.
PMID- 28511525
TI - Rehabilitation of a Patient with Facial and Palatal Defect - A Case Report.
AB - Defects involving the face and maxilla present a challenge to the prosthodontists
as these have a direct effect on aesthetics, function as well as the psychology
of the patient. An array of problems awaits the clinician from restoring the
previous contour of the oral cavity, facial form, etc. to the mental state of the
patients. This article deals with the rehabilitation of a hemimaxillectomy
patient with a facial defect, using an interim hollow bulb obturator and a
silicone facial prosthesis, which helped to improve the general well being of the
patient. Rehabilitative procedures provide patients considerable care so that
they can continue their life with confidence.
PMID- 28511524
TI - Basaloid Squamous Cell Carcinoma of Tongue: A Report with Emphasis on
Immunohistochemistry.
AB - Basaloid Squamous Cell Carcinoma (BSCC) is a rare entity with its
histopathological distinction from conventional squamous cell carcinoma. It is
frequently considered a high-grade carcinoma with poor prognosis because of
higher rate of distant metastases. Here by, we are reporting a case of 39-year
old male with an ulcer on the left lateral border of the tongue since a month.
Histopathological examination of incisional biopsy revealed basaloid tumour cell
islands accompanied by component of well differentiated squamous cell carcinoma.
To reconfirm this incidental finding immunohistochemistry was carried out for
Proliferative Cell Nuclear Antigen (PCNA) and pancytokeratin (AE1/AE3) which was
positive to conclude diagnosis of BSCC. Further p16 staining was done to rule out
Human Papilloma Virus (HPV) infection.
PMID- 28511526
TI - Angiolymphoid Hyperplasia with Eosinophilia Involving the Occipital Artery: Case
Report and Review of Literature.
AB - Angiolymphoid Hyperplasia with Eosinophilia (ALHE) is an atypical vascular tumour
occurring primarily in the head and neck area, which must be distinguished from
Kimura's disease. The lesions can appear as single or multiple grouped
intradermal papules or subcutaneous nodules. We report a rare case of ALHE in a
57-year-old female with a large lesion of three nodules involving the right
occipital artery which had a long term evolution and we treated it by surgical
excision. The definitive histopathological diagnosis was ALHE. Our case report is
accompanied by a discussion of clinical, radiological and histological features.
Surgical excision with free margins is the treatment of choice but, even though
ALHE is considered a benign condition, recurrence is common.
PMID- 28511527
TI - Temporary Blindness after Inferior Alveolar Nerve Block.
AB - Inferior Alveolar Nerve Block (IANB) anaesthesia is one of the common procedures
in dental clinic. This procedure is safe, but complications may still occur.
Ocular complications such as diplopia, loss of vision, or ophthalmoplegia are
extremely rare. This case report explains an event where due to individual
anatomic variation of the sympathetic vasoconstrictor nerve and maxillary and
middle meningeal arteries, intravascular administration of anaesthetic agent
caused unusual ocular signs and symptoms such as temporary blindness.
PMID- 28511528
TI - Immediate Placement of Zirconia Implants in Teeth with Periapical Lesions: A Case
Report.
AB - This case report records the replacement of two failed endodontically treated
mandibular molars with one piece zirconia implants in a patient with metal
hypersensitivity. The two molars were atraumatically extracted and curetted to
remove any remnants of a periapical granuloma. Immediate implant placement with
primary stability was achieved using one piece WhiteSky(r) Bredent zirconia
implants which were restored after four months with a zirconia crown. One year
follow up revealed successful osseointegration with optimal form and function.
PMID- 28511529
TI - Orthodontic Therapy for Paediatric Cancer Survivors: A Review.
AB - The paper aims at reviewing the possibilities of orthodontic therapy for
paediatric cancer survivors. It is important to understand the fundamental
disease, it's treatment protocols, effects on growing skeleton, dental
development, oral cavity and oral mucosa, dental caries, bone, orthodontic tooth
movement.
PMID- 28511531
TI - Occurrence of Cusp of Carabelli in Primary Second Molar Series of three Cases.
AB - Morphological variations are seen in both primary and permanent dentitions. Cusp
of Carabelli is also one of them. It is suggested that it is due to over activity
of dental lamina but definitive aetiology is unknown. It is a type of accessory
cusp, occurs more often in permanent maxillary first molars, whereas, its
occurrence in primary tooth is rare. The present case series discusses the
presence of cusp of Carabelli in primary maxillary second molars in three
different cases. This case series will help clinicians to identify, diagnose and
take proper preventive care and also adds to the incidence in literature.
PMID- 28511530
TI - Herbs in Oral Mucositis.
AB - Oral mucositis is an inflammatory mucosal destruction as a result of chemotherapy
and/or radiation therapy, which in severe cases can impair patients' quality of
life. Moreover, mucosal infection and/or systemic involvement due to compromised
immunity leads to delay or discontinuation of the treatment. Many strategies and
agents have been suggested for the management of this condition. Because of their
lower side effects compared to chemical drugs, general interest in evaluating
therapeutic effects of herbs has been increased intensively. Herbal plants apply
their effect through different mechanisms of action: antioxidant, analgesic, anti
inflammatory, antifungal, antiseptic, and anticarcinogenic activity. Recently,
various natural agents in plants have been noticed in mucositis, which may
improve the symptoms through different interventions. The purpose of this review
is to focus on the preventive or therapeutic use of herbal medicine to alleviate
oral mucositis.
PMID- 28511532
TI - Kedo-S Paediatric Rotary Files for Root Canal Preparation in Primary Teeth - Case
Report.
AB - Nickel-Titanium (Ni-Ti) instrument are widely used for root canal preparation in
permanent tooth compared to primary teeth. Hand instrumentation technique remains
the conventional method for root canal preparation in primary teeth. The time
taken for root canal preparation with the conventional method is more resulting
in patients and clinicians fatigue. Recently Ni-Ti rotary files designed for
permanent tooth has been used for root canal preparation in primary teeth. Using
rotary instruments for primary tooth pulpectomies resulted in better and
predictable root canal filling. This article presents case reports of pulpectomy
treatment performed using Kedo-S an exclusive paediatric Ni-Ti rotary files. The
advantages and disadvantages in use of Ni-Ti rotary files in primary teeth are
discussed in this article.
PMID- 28511533
TI - Composition, Morphology, and Topography of Galvanic Coatings Fe-Co-W and Fe-Co
Mo.
AB - Ternary coatings Fe-Co-W with an iron content of 40-55 at.%, cobalt 39-44 at.%,
and tungsten 4-12 at.% and Fe-Co-Mo with an iron content of 40-55 at.%, cobalt 39
44 at.%, and tungsten 4-12 at.% were obtained by galvanostatic and pulse
electrolysis on the mild steel substrate from iron(III) citrate-based
electrolyte. The influence of electrolysis mode and parameters on composition of
deposited alloys was studied. The competing reduction of iron and tungsten in Fe
Co-W coatings as well as the competitive deposition of iron and cobalt in Fe-Co
Mo coatings at various current densities were defined. Simultaneously, the alloy
enrichment with molybdenum is more marked at a pulse mode. Atomic force
microscope analysis of the Fe-Co-W alloy coating morphology and surface
topography indicates their globular structure with spherical grains in the range
of 2.5-3.5 MUm. The surface of Fe-Co-Mo is characterized by parts of a globular
structure with an average conglomerate size of 0.3-0.5 MUm and singly located
cone-shaped hills with a base diameter of 3 MUm. Sites with a developed surface
were detected within the same scan area which topography is identical to the
crystal lattice of cobalt with the crystalline conglomerate sizes in the range of
0.2-1.75 MUm.
PMID- 28511534
TI - Ferroelectric domain states of a tetragonal BiFeO3 thin film investigated by
second harmonic generation microscopy.
AB - We investigate the ferroelectric state of a tetragonal BiFeO3 thin film grown on
a LaAlO3 (001) substrate using an optical second harmonic generation (SHG)
microscope. Whereas the ferroelectric state of this material hosts nanometer
sized domains which again form micrometer-sized domains of four different
configurations, we could figure out the characteristic features of each domain
from the SHG mapping with various sizes of the probe beam, i.e., from 0.7 to 3.9
MUm in its diameter. In particular, we demonstrate that a single micrometer-sized
domain contributes to the SHG as a coherent summation of the constituent
nanometer-sized domains, and multi-micrometer-sized domains contribute to the SHG
as an incoherent summation of each micro-domain.
PMID- 28511535
TI - Surface Morphology Evolution Mechanisms of InGaN/GaN Multiple Quantum Wells with
Mixture N2/H2-Grown GaN Barrier.
AB - Surface morphology evolution mechanisms of InGaN/GaN multiple quantum wells
(MQWs) during GaN barrier growth with different hydrogen (H2) percentages have
been systematically studied. Ga surface-diffusion rate, stress relaxation, and H2
etching effect are found to be the main affecting factors of the surface
evolution. As the percentage of H2 increases from 0 to 6.25%, Ga surface
diffusion rate and the etch effect are gradually enhanced, which is beneficial to
obtaining a smooth surface with low pits density. As the H2 proportion further
increases, stress relaxation and H2 over- etching effect begin to be the dominant
factors, which degrade surface quality. Furthermore, the effects of surface
evolution on the interface and optical properties of InGaN/GaN MQWs are also
profoundly discussed. The comprehensive study on the surface evolution mechanisms
herein provides both technical and theoretical support for the fabrication of
high-quality InGaN/GaN heterostructures.
PMID- 28511536
TI - Biomimetic Silica Nanocapsules for Tunable Sustained Release and Cargo
Protection.
AB - Silica nanocapsules have attracted tremendous interest for encapsulation,
protection, and controlled release of various cargoes due to their unique
hierarchical core-shell structure. However, it remains challenging to synthesize
silica nanocapsules having high cargo-loading capacity and cargo-protection
capability without compromising process simplicity and biocompatibility
properties. Here, we synthesized oil-core silica-shell nanocapsules under
environmentally friendly conditions by a novel emulsion and biomimetic dual
templating approach using a dual-functional protein, in lieu of petrochemical
surfactants, thus avoiding the necessities for the removal of toxic components. A
light- and pH-sensitive compound can be facilely encapsulated in the silica
nanocapsules with the encapsulation efficiency of nearly 100%. Release of the
encapsulated active from the nanocapsules was not shown an indication of
undesired burst release. Instead, the release can be tuned by controlling the
silica-shell thicknesses (i.e., 40 and 77 nm from which the cargo released at
42.0 and 31.3% of the initial amount after 32 days, respectively). The release
kinetics were fitted well to the Higuchi model, enabling the possibility of the
prediction of release kinetics as a function of shell thickness, thus achieving
design-for-purpose silica nanocapsules. Furthermore, the nanocapsules showed
excellent alkaline- and sunlight-shielding protective efficacies, which resulted
in significantly prolonged half-life of the sensitive cargo. Our biomimetic
silica nanocapsules provide a nanocarrier platform for applications that demand
process scalability, sustainability, and biocompatibility coupled with unique
cargo-protection and controlled-release properties.
PMID- 28511538
TI - Phonon-like Hydrogen-Bond Modes in Protic Ionic Liquids.
AB - Gigahertz- to terahertz-frequency infrared and Raman spectra contain a wealth of
information concerning the structure, intermolecular forces, and dynamics of
ionic liquids. However, these spectra generally have a large number of
contributions ranging from slow diffusional modes to underdamped librations and
intramolecular vibrational modes. This makes it difficult to isolate effects such
as the role of Coulombic and hydrogen-bonding interactions. We have applied far
infrared and ultrafast optical Kerr effect spectroscopies on carefully selected
ions with a greater or lesser degree of symmetry in order to isolate spectral
signals of interest. This has allowed us to demonstrate the presence of
longitudinal and transverse optical phonon modes and a great similarity of
alkylammonium-based protic ionic liquids to liquid water. The data show that such
phonon modes will be present in all ionic liquids, requiring a reinterpretation
of their spectra.
PMID- 28511537
TI - Terminal Acetylated/Acrylated Poly(ethylene glycol) Fabricated Drug Carriers:
Design, Synthesis, and Biological Evaluation.
AB - The simple acetylation or acrylation of poly(ethylene glycol) (PEG) terminus
leads to the aggregation of PEG chains into spherical nanoparticles in water at
room temperature and very low concentrations. The experiment results suggest that
this aggregation happens by the variation of the local conformation of the O-CH2
CH2-O segments of PEG chains caused by the introduced acyl group, which disturbs
the originally strict hydrogen bond mode between the O-CH2-CH2-O groups and the
water molecules. The simple modified PEG nanoparticles are excellent carriers for
drug delivery. As examples, the cross-linkable 1d-based drug delivery systems,
cPEG@SN-38 and targeted cPEG@SN-38, are successfully established by their high
drug loading content (18 wt %/wt) and enhanced anticancer efficacy both in vitro
and in vivo while obviating the inherent toxicity of the employed
chemotherapeutics. This strategy that revolves around the simple modification of
the generally regarded as safe (GRAS) modules to fabricate drug carriers
represents a new direction for the drug delivery systems with clinical potential.
PMID- 28511539
TI - Exploiting Salt Induced Microphase Separation To Form Soy Protein Microcapsules
or Microgels in Aqueous Solution.
AB - Self-assembly of native glycinin at room temperature was investigated as a
function of the pH and the NaCl concentration. Microphase separation leading to
the formation of dense protein microdomains was observed by confocal laser
scanning microscopy. Depending on the conditions, the microdomains coalesced into
a continuous protein rich phase or associated into large clusters. Addition of
beta-conglycinin inhibited phase separation and reduced the pH range in which it
occurred. Microdomains of glycinin that were formed in the presence of 0.1 M NaCl
transformed into hollow stable cross-linked microcapsules when heated above 60
degrees C with diameters between 3 and 30 MUm depending on the protein
concentration and a shell thickness between 1.0 and 1.4 MUm. The microcapsules
were stable to dilution in salt free water, whereas microdomains formed at room
temperature redispersed. Microdomains formed in mixtures with beta-conglycinin
did not transform into microcapsules, but they became stable cross-linked
homogeneous microgels.
PMID- 28511540
TI - Effects of Water-Extractable Arabinoxylan on the Physicochemical Properties and
Structure of Wheat Gluten by Thermal Treatment.
AB - This study investigated the effects of water-extractable arabinoxylan (WEAX) on
gluten by thermal treatment. Fourier transform infrared spectroscopy (FTIR)
results showed that heating significantly decreased beta-sheets and beta-turn
structures in gluten proteins between 25 and 55 degrees C. The addition of WEAX
caused a transition from beta-turn to beta-sheets at >55 degrees C. The ratio of
weakly hydrogen-bonded beta-sheets to strongly hydrogen-bonded beta-sheets
demonstrated an increasing trend with temperature increasing, but WEAX can hinder
this process. FT-Raman results revealed that a hydrophilic environment was
developed with 5% WEAX at 25 degrees C, and phenolic hydroxyl on ferulic acid
can form new H-bonds with the phenyl groups of the nondissociated Tyr residues. A
5% WEAX content is helpful for gluten to maintain its original gauche-gauche
gauche conformation of disulfide bond upon heating. In addition, WEAX can reduce
the elasticity of gluten and form a soft texture at 25, 55, and 75 degrees C.
PMID- 28511543
TI - Sterilization, hydration-dehydration and tube fabrication of zwitterionic
hydrogels.
AB - Terminal sterilization of hydrogel-based biomaterials is crucial for their
clinically relevant applications. The authors synthesized nonfouling zwitterionic
hydrogels consisting of carboxybetaine (CB) acrylamide monomer and a
carboxybetaine dimethacrylate crosslinker. The mechanical and biological
stability of nonfouling hydrogels were investigated using three main terminal
sterilization techniques, i.e., steam autoclave, ethylene oxide gas, and gamma
irradiation. It was found that CB hydrogels are very stable at high temperature
and pressure and in oxidative gas environments without changing their stress,
modulus, and nonfouling properties. Gamma irradiation of CB hydrogels in dry
state showed high mechanical and nonfouling stability by avoiding the adverse
effect of the free radicals resulted from water inside the hydrogel network. The
CB hydrogels can be dehydrated and hydrated back and forward reversibly in
several cycles without any loss in mechanical properties, which is desirable for
hydrogel storage, handling, and sterilization. The CB hydrogel tubes are easily
prepared using a simple procedure, and they are uniformly transparent and tough
after swelling. Furthermore, the good mechanical properties of the CB hydrogel
tubes and their resistance to red blood cells indicate great potential of this
nonfouling material for medical applications.
PMID- 28511544
TI - Structural characterization of membrane-bound human immunodeficiency virus-1 Gag
matrix with neutron reflectometry.
AB - The structural characterization of peripheral membrane proteins represents a
tremendous challenge in structural biology due to their transient interaction
with the membrane and the potential multitude of protein conformations during
this interaction. Neutron reflectometry is uniquely suited to address this
problem because of its ability to structurally characterize biological model
systems nondestructively and under biomimetic conditions that retain full protein
functionality. Being sensitive to only the membrane-bound fraction of a water
soluble peripheral protein, neutron reflectometry obtains a low-resolution
average structure of the protein-membrane complex that is further refined using
integrative modeling strategies. Here, the authors review the current
technological state of biological neutron reflectometry exemplified by a detailed
report on the structure determination of the myristoylated human immunodeficiency
virus-1 (HIV-1) Gag matrix associated with phosphoserine-containing model
membranes. The authors found that the HIV-1 Gag matrix is able to adopt different
configurations at the membrane in a pH-dependent manner and that the myristate
group orients the protein in a way that is conducive to PIP2-binding.
PMID- 28511546
TI - The Relationship Between Work Commitment, Dynamic, and Medication Error.
AB - Incidence of medication errors in intensive care unit (ICU) can cause irreparable
damage for ICU patients. Therefore, it seems necessary to find the causes of
medication errors in this section. Work commitment and dynamic might affect the
incidence of medication errors in ICU. To assess the mentioned hypothesis, we
performed a descriptive-analytical study which was carried out on 117 nurses
working in ICU of educational hospitals in Tehran. Minick et al., Salyer et al.,
and Wakefield et al. scales were used for data gathering on work commitment,
dynamic, and medication errors, respectively. Findings of the current study
revealed that high work commitment in ICU nurses caused low number of medication
errors, including intravenous and nonintravenous. We controlled the effects of
confounding variables in detection of this relationship. In contrast, no
significant association was found between work dynamic and different types of
medication errors. Although the study did not observe any relationship between
the dynamics and rate of medication errors, the training of nurses or nursing
students to create a dynamic environment in hospitals can increase their interest
in the profession and increase job satisfaction in them. Also they must have
enough ability in work dynamic so that they don't confused and distracted result
in frequent changes of orders, care plans, and procedures.
PMID- 28511545
TI - Fosfomycin tromethamine for the Treatment of Cystitis in Abdominal Solid Organ
Transplant Recipients With Renal Dysfunction.
AB - BACKGROUND: Urinary tract infection (UTI) after abdominal solid organ
transplantation (SOT) is associated with significant morbidity and mortality.
Fosfomycin tromethamine (FOS), a uroselective antibiotic, is FDA approved for
uncomplicated UTIs in women and is used off-label for complicated UTIs and
prostatitis in men. Literature supporting the use of FOS in the SOT population is
limited, and efficacy is questioned in the setting of renal dysfunction.
OBJECTIVE: To evaluate the success of FOS for the treatment of cystitis in SOT
patients with renal dysfunction. METHODS: This was a single-center, retrospective
study using medical records. SOT recipients receiving at least 1 dose of FOS for
treatment of cystitis between January 1, 2009, and April 30, 2015, were included.
Treatment outcomes were analyzed with respect to renal function. RESULTS: A total
of 76 courses of FOS were identified in 64 patients. The renal dysfunction arm
(creatinine clearance [CrCl] < 40 mL/min) included 33 patients with 39 FOS
courses; the normal renal function arm (CrCl >= 40 mL/min) included 31 patients
with 37 FOS courses. Mean CrCl was 23.3 +/- 9.7 mL/min for the renal-dysfunction
group and 65 +/- 29.3 mL/min for the normal renal function group ( P < 0.01). No
significant difference in treatment success was noted between CrCl <40 mL/min and
CrCl >=40 mL/min (31 [80%] vs 34 [92%], P = 0.12) in a unilateral analysis. After
adjusting for confounders in a multivariable analysis, there was no difference in
the risk of failure between CrCl <40 mL/min and CrCl >=40 mL/min groups ( P =
0.70). CONCLUSION: FOS appears to be successful for the treatment of cystitis in
SOT recipients in the setting of renal dysfunction.
PMID- 28511548
TI - Quality-adjusted life year difference in patients with predominant negative
symptoms of schizophrenia treated with cariprazine and risperidone.
AB - AIM: Our study aimed at estimating differences in quality-adjusted life year
(QALY) gain for patients with predominant negative symptoms of schizophrenia
treated with cariprazine compared with risperidone. MATERIALS & METHODS: A Markov
model was built, based on the Mohr-Lenert approach and data derived from clinical
trials, to estimate potential QALY gains of patients. RESULTS: Patients had
higher probability of reaching better health states treated with cariprazine
compared with risperidone. In the model, this resulted in an estimated QALY gain
of 0.029 per patient, after 1 year of treatment. CONCLUSION: Cariprazine, which
showed clinically meaningful improvement in the symptoms, and personal and social
performance, can also provide significant QALY gain in the treatment of patients
with predominant negative symptoms of schizophrenia compared with risperidone.
PMID- 28511547
TI - Smell and Taste Impairment After Total Laryngectomy.
AB - OBJECTIVE: Aim of this observational study is the evaluation of olfactory and
gustatory impairments in laryngectomized long-term survivors compared to control
subjects. Correlation between smell and taste alterations, age, and previous
adjuvant treatments in laryngectomees was investigated. METHODS: Fifty control
subjects and 50 patients who underwent total laryngectomy for advanced laryngeal
carcinoma were evaluated. All subjects underwent symptoms evaluation,
oropharyngeal exam, endoscopic fiberoptic nasal examination, and Taste Strips and
Sniffin' Sticks tests. RESULTS: Hyposmia was reported by all laryngectomees and
hypogeusia by 54% of patients. Sniffin' Sticks and Taste Strips tests
demonstrated a statistically significant difference between controls and
laryngectomees regarding olfactory threshold, odor discrimination and
identification, Threshold Discrimination Identification (TDI) score, and sour,
salty, and gustatory Total Taste score ( P < .05). Multivariate analysis for
Total Taste score in laryngectomees showed a statistically significant
correlation with aging, having an odds ratio of 0.127 for age >=65 years, but not
with TDI score, radiotherapy, and follow-up time, whereas multivariate analysis
for TDI score demonstrated no correlation with radiotherapy, age, and follow-up
time. CONCLUSIONS: Total laryngectomy determines olfactory and gustatory
impairments that should be taken into account in clinical practice. Relationships
between sensorial alterations, aging, follow-up period, and adjuvant treatments
should be further evaluated in prospective studies.
PMID- 28511550
TI - CT features in surgically proven cases of ovarian torsion-a pictorial review.
AB - Ovarian torsion is a surgical emergency characterized by a partial or complete
rotation of the ovarian vascular pedicle, causing obstruction to venous outflow
followed by arterial inflow. Clinically, ovarian torsion frequently mimics other
causes of acute pelvic pain such as appendicitis, diverticulitis, renal colic
etc. Ultrasonography is the first-line imaging modality of choice for evaluation
of ovarian torsion. MRI is useful as a problem-solving tool in patients with
equivocal or non-diagnostic ultrasonography studies. CT is ordinarily not
utilized in a young female with suspected ovarian torsion due to the radiation
dose. However, the significant expansion in use of CT imaging in emergency
departments for female patients presenting with acute abdominal pain has
increased the likelihood that ovarian torsion may be first seen on CT. In
addition, a non-specific clinical presentation may lead to an initial imaging
with CT rather than ultrasonography. Ultrasound features of the ovarian torsion
are well known and sufficiently described across literature as compared with the
CT scan findings. In view of the increasing usage of CT as the modality of choice
in emergency settings, it is imperative for the radiologist to familiarize with
the CT features of ovarian torsion. An early correct diagnosis by the radiologist
in clinically unsuspected cases, facilitating a prompt surgery to restore the
ovarian blood flow can prevent permanent irreversible damage. There is limited
published data available on the CT features of ovarian torsion. This pictorial
essay illustrates CT findings with histological correlation of surgically proven
ovarian torsion in our institution. These patients were primarily investigated
with CT scan for acute pelvic pain ascribed to non-gynaecological causes such as
bowel or urinary tract lesions.
PMID- 28511549
TI - Radiological findings on irradiation-CT in patients with non metastatic breast
cancer.
AB - OBJECTIVE: The aim of this study was to evaluate the number of incidental
findings on native CT treatment-planning scans for radiation in breast cancer
patients. METHODS: The treatment-planning scans of 382 patients with non
metastatic breast cancer were retrospectively analyzed for additional findings.
The planning scan area covered the entire thorax and the upper part of the
abdomen. Incidental findings were classified according to their clinical
relevance. RESULTS: Overall 892 incidental findings were detected in the CT
treatment-planning scans (mean 2.34 findings per patient). Only a small
proportion of patients (n = 63, 16.4%) had no finding. Most findings were located
in the thorax (683, 76.57%), and 209 findings (23.43%) were abdominal. 79
findings (8.87%) were of major clinical relevance, 232 findings (26.01%) were of
moderate clinical relevance and 580 findings (65.02%) were of minor clinical
relevance. Most clinically relevant findings were in the thorax (p = 0.006).
Abdominal findings were more of significantly minor clinical relevance (p <
0.0001). CONCLUSION: Radiological findings are frequent in native CT treatment
planning scans for radiation of breast cancer patients. Therefore, the
radiologist should use this performed sectional image to obtain additional
information of the patient. Advances in knowledge: Treatment-planning CT scans
can show several radiological findings, namely 2.34 findings per patient. Major
clinically relevant findings account for 8.87%.
PMID- 28511551
TI - Theoretical Foundations of Appeals Used in Alcohol-Abuse and Drunk-Driving Public
Service Announcements in the United States, 1995-2010.
AB - PURPOSE: The study identifies the extent to which theoretical constructs drawn
from well-established message effect communication theories are reflected in the
content of alcohol-related public service announcements (PSAs) airing in the
United States over a 16-year period. DESIGN: Content analysis of 18 530 141
alcohol-abuse (AA) and drunk-driving (DD) PSAs appearing on national network and
local cable television stations in the 210 largest designated marketing areas
(DMAs) from January 1995 through December 2010. MEASURES: The authors developed a
detailed content analytic codebook and trained undergraduate coders to reliably
identify the extent to which theoretical constructs and other creative ad
elements are reflected in the PSAs. We show these patterns using basic
descriptive statistics. RESULTS: Although both classes of alcohol-related PSAs
used strategies that are consistent with major message effect theories, their
specific theoretical orientations differed dramatically. The AA PSAs were
generally consistent with constructs emphasized by the Extended Parallel Process
Model (EPPM), whereas DD PSAs were more likely to use normative strategies
emphasized by the Focus Theory of Narrative Conduct (FTNC) or source credibility
appeals central to the Elaboration Likelihood Model. CONCLUSION: Having
identified message content, future research should use deductive approaches to
determine if volume and message content of alcohol-control PSAs have an impact on
measures of alcohol consumption and/or measures of drunk driving, such as
fatalities or driving while intoxicated/driving under the influence arrests.
PMID- 28511552
TI - R147W in PROC Gene Is a Risk Factor of Thromboembolism in Thai Children.
AB - The p.R147W mutation, the c.C6152T in exon 7, causing a change in amino acid from
arginine to tryptophan of the PROC gene has been reported as a common mutation in
Taiwanese populations with venous thromboembolism (VTE). The present study aimed
to identify the prevalence of p.R147W in the Thai population and children with TE
and the risk of developing TE. Patients aged <=18 years diagnosed with TE were
enrolled. The PROC gene was amplified by polymerase chain reaction using a
specific primer in exon 7. The restriction fragment length polymorphism was
designed using MwoI restriction enzyme. A total of 184 patients and 690 controls
were enrolled. The most common diagnosis of TE was arterial ischemic stroke
(AIS), at 100 (54.3%), followed by VTE, at 38 (20.6%), and cerebral venous sinus
thrombosis (CVST), at 23 (12.5%). The prevalence of heterozygous and homozygous
p.R147W in patients and controls was 9.5% versus 5.8% and 2.7% versus 0.1%,
respectively. Heterozygous p.R147W had odds ratios (ORs) of 1.8 (95% confidence
interval [CI]: 1.0-3.2, P = .04), 3.2 (95% CI: 1.2-8.2, P = .009), and 4.5 (95%
CI: 1.6-12.8, P = .002) of developing overall TE, VTE, and CVST, respectively.
Homozygous p.R147W had ORs of 20.2 (95% CI: 2.3-173.7, P < .001), 21.4 (95% CI:
2.2-207.9, P < .001), and 43.3 (95% CI: 3.8-490.6, P < .001) of developing
overall TE, AIS, and CVST, respectively. This study suggested that p.R147W is a
common mutation and increased risk of TE in Thai children.
PMID- 28511553
TI - Whole Blood Platelet Aggregation Test and Prediction of Hemostatic Difficulty
After Tooth Extraction in Patients Receiving Antiplatelet Therapy.
AB - When patients on antiplatelet therapy (APT) require minor invasive surgery, APT
is usually continued to limit the risk of thrombosis. However, the possibility of
hemostatic difficulties necessitates the monitoring of platelet aggregation to
prevent unexpected bleeding. We examined whether whole blood aggregometry as a
point-of-care testing (POCT) could be useful as a tool for predicting hemostatic
difficulties. Sixty-five patients receiving APT and 15 patients who were not
receiving APT were enrolled in the present study; all patients were scheduled to
undergo a tooth extraction. Whole blood samples were obtained and were examined
using multiple electrode aggregometry. The aggregometry was performed using
arachidonic acid (AA), adenosine diphosphate (ADP), and thrombin receptor
activating peptide. Hemostatic difficulty was defined as a need for more than 10
minutes of compression to achieve hemostasis. The AA test results were
significantly lower in patients treated with aspirin (control: 97.7 [29.0] U,
aspirin: 14.5 [7.2] U, P < .001). The ADP test results were also significantly
lower in patients treated with a P2Y12 inhibitor (control: 77.7 [21.7] U, P2Y12
inhibitor: 37.3 [20.4] U, P < .01). Six of the examined cases exhibited
hemostatic difficulties. The cutoff values for the prediction of hemostatic
difficulty were 16.5 U for the AA test (sensitivity, 0.833; specificity, 0.508)
and 21 U for the ADP test (sensitivity, 0.847; specificity, 0.500). Our study
showed that whole blood aggregometry was useful as a POCT for the prediction of
hemostatic difficulties after tooth extraction in patients receiving APT.
PMID- 28511554
TI - Resveratrol promotes recovery of immune function of immunosuppressive mice by
activating JNK/NF-kappaB pathway in splenic lymphocytes.
AB - Resveratrol, a natural compound found in over 70 plants, is known to possess
immunoregulatory effects and anti-inflammatory activity. It has been shown that
resveratrol has regulatory effects on different signaling pathways in different
diseases. However, few reports have evaluated the effects of resveratrol on
reinforcing immunity recovery via activating nuclear factor-kappaB (NF-kappaB)
pathway and Jun N-terminal kinases (JNK) pathway. The present study aimed to
assess immune-enhancing activity and underlying mechanism of resveratrol in
immunosuppressive mice. Previously, we reported that resveratrol could promote
mouse spleen lymphocyte functions to recover the immune system effectively. In
the present study, we show that resveratrol could upregulate the expressions of
NF-kappaB, IkappaB kinase, JNK, and c-jun in splenic lymphocytes of
immunosuppressive mice. Taken together, our results indicate that resveratrol
could promote recovery of immunologic function in immunosuppressive mice by
activating JNK/NF-kappaB pathway.
PMID- 28511557
TI - Impact of a Perioperative Prophylaxis Guideline on Post-Cardiothoracic Surgery
Atrial Fibrillation.
AB - BACKGROUND: National practice guidelines do not provide clear recommendations on
combination pharmacological regimens to reduce cardiothoracic surgery (CTS)
postoperative atrial fibrillation (POAF). OBJECTIVE: This study examines if there
is a reduction in POAF rates after implementing a perioperative prophylaxis
guideline that includes amiodarone, beta-blockers, and high-intensity statins.
METHODS: Data were retrospectively collected on 400 adults (200 patients pre
guideline implementation and 200 patients post-guideline implementation) with a
CHA2DS2-VASc (Congestive Heart Failure, Hypertension, Age, Diabetes Mellitus, and
Vascular Disease) score of at least 3 points after CTS. Data were collected on
the incidence of POAF lasting more than 5 minutes and secondary outcomes,
including the length of hospitalization, guideline adherence rate, adverse
events, and timeliness of POAF treatment. RESULTS: Guideline implementation
increased prophylactic amiodarone ( P < 0.0001), statin ( P = 0.029), and high
intensity statin ( P = 0.002) use without changing beta-blocker use (64.5% vs
67.0%, P = 0.673) and reduced POAF (39.5% vs 52.0%, P = 0.016) and ventricular
tachycardia (15.5% vs 24.5%, P = 0.034) compared with preguideline rates. Length
of hospitalization and other postoperative adverse events, including stroke and
mortality, were not statistically different. Subgroup analyses of patients who
were adherent to both the amiodarone and beta-blocker recommendations (28% of the
total) or to all 3 recommended therapies (24% of the total) had significant
decreases in POAF ( P = 0.001; P < 0.001), length of hospitalization ( P = 0.023;
P = 0.049), length of intensive care unit stay ( P = 0.045; P = 0.040), and
ventricular tachycardia ( P = 0.008; P = 0.017) compared with preguideline
patients, respectively. CONCLUSIONS: A perioperative guideline of amiodarone,
beta-blockers, and high-intensity statins reduced POAF, but better benefits may
result from enhanced adherence.
PMID- 28511558
TI - Three new indole alkaloid derivatives from the roots of Murraya paniculata.
AB - Three new indole alkaloid derivatives, named paniculidines D-F (1-3), and six
known analogs (4-9) were isolated from the roots of Murraya paniculata. The
structures were elucidated on the basis of comprehensive HRESIMS, UV, IR, and NMR
spectroscopic data analysis and comparison with the data reported in literature.
The absolute configurations of new compounds were assigned via the determination
of specific optical rotation, Mosher's method, and ECD spectra. Compound 3 is the
first heterodimer of C-N linked indole and coumarin derivatives.
PMID- 28511556
TI - Performance and digestive function of broiler chickens given grit in the diet.
AB - 1. A series of experiments were carried out to study the effect of grit on
broiler performance, gizzard development and fate of grit in the digestive tract.
2. In Experiment 1, performance, gizzard weight and content of grit in the
gizzard of broiler chickens given access to granite-type grit was investigated.
In Experiment 2, the effect of grit stones on performance and gizzard development
was assessed in diets with or without whole wheat. 3. In Experiment 3, the effect
of grit in the form of zeolite, granite or marble on gizzard development and
digestive tract grinding and passage was studied in diets with or without whole
wheat. 4. Grit stones had no effect on performance of broiler chickens, which may
be explained by the fact that grit stones did not stimulate gizzard development
to the same extent as with other structural materials. 5. The lack of stimulation
is at least partly due to the fact that a majority of the grit stones eaten pass
through the small intestine without being retained in the gizzard. 6. Grit in the
form of marble reduced feed intake and weight gain.
PMID- 28511559
TI - Migrating microbes: what pathogens can tell us about population movements and
human evolution.
AB - BACKGROUND: The biology of human migration can be observed from the co
evolutionary relationship with infectious diseases. While many pathogens are
brief, unpleasant visitors to human bodies, others have the ability to become
life-long human passengers. The story of a pathogen's genetic code may,
therefore, provide insight into the history of its human host. The evolution and
distribution of disease in Africa is of particular interest, because of the deep
history of human evolution in Africa, the presence of a variety of non-human
primates, and tropical reservoirs of emerging infectious diseases. METHODS: This
study explores which pathogens leave traces in the archaeological record, and
whether there are realistic prospects that these pathogens can be recovered from
sub-Saharan African archaeological contexts. RESULTS: Three stories are then
presented of germs on a journey. The first is the story of HIV's spread on the
back of colonialism and the railway networks over the last 150 years. The second
involves the spread of Schistosoma mansoni, a parasite which shares its history
with the trans-Atlantic slave trade and the origins of fresh-water fishing.
Finally, we discuss the tantalising hints of hominin migration and interaction
found in the genome of human herpes simplex virus 2. CONCLUSIONS: Evidence from
modern African pathogen genomes can provide data on human behaviour and migration
in deep time and contribute to the improvement of human quality-of-life and
longevity.
PMID- 28511560
TI - Synthesis and in vitro antitumour activities of lupeol derivatives.
AB - Nine lupeol derivatives were synthesised and assayed in vitro for their
antitumour activities against three human tumour cells lines, A549, LAC and
HepG2. Of lupeol derivaties, six were new compounds, and five compounds against
A549 cells, four compounds against HepG2 cells and three compounds against LAC
cells were effective in reducing viability, and the most promising compounds 5, 6
and 9 exhibited high activities against lung and liver cancer cells, even higher
activities than those of adriamycin.
PMID- 28511561
TI - Depression of the maxillary sinus anterior wall and its influence on panoramic
radiography appearance.
AB - OBJECTIVES: To clarify the depression aspect of the maxillary sinus anterior wall
and to investigate its relationship with the panoramic image appearance of a
diagonal line from the inferior part of the so-called panoramic innominate line
to the medial portion of the orbital floor line. METHODS: Based on CT data,
panoramic images were simulated for two typical cases with and without anterior
wall depression. Next, on axial CT images of 1689 subjects (3378 sinuses) stored
in our image database, the wall depths were measured and analyzed for their
relationships with the panoramic appearances of the diagonal line, classified
into invisible, obscure and clear patterns. RESULTS: Based on the simulation
study, visualization of the diagonal line was verified to alter depending on the
morphology of the anterior wall and the position of the panoramic image layer. In
408 (12.1%) sinuses, the diagonal line (clear and obscure patterns) could be seen
on the panoramic image. The incidences of the obscure and clear patterns
increased with increasing age groups. The mean wall depths were 2.91, 4.80 and
7.28 mm for the invisible, obscure and clear patterns, respectively. The clear
pattern showed the highest value for the wall depth, followed by the obscure
pattern. CONCLUSIONS: The diagonal line on a panoramic image was verified to be
related to depression of the maxillary sinus anterior wall, and its panoramic
image appearance can be altered depending on the position of the tomographic
image layer.
PMID- 28511562
TI - A review of cognitive remediation approaches for schizophrenia: from top-down to
bottom-up, brain training to psychotherapy.
AB - INTRODUCTION: Individuals with psychotic disorders experience profound impairment
in neurocognition, which is consistently found to be the best predictor of
independent community functioning. Several diverse behavioural treatments
designed to enhance neurocognitive abilities have been developed, with subtle to
stark differences among them. Various approaches, to varying degrees, have
demonstrated success across diffuse outcomes: improved brain structure and
function, performance on neuropsychological tests, and community activities
associated with daily living. Areas covered: This paper reviews the different
approaches to cognitive remediation and the differential effects these approaches
have on neurophysiological function, neurocognitive abilities, and real-world
community functioning. Cognitive remediation approaches can be broadly classified
along two dimensions: 1) treatment target, and 2) treatment modality. Some
approaches target more basic perceptual skills, some target higher level
executive processes, while some are non-targeted and seek to improve general
cognitive ability. With regard to modality, approaches might have little/no
therapist involvement and rely exclusively on computerized practice or they may
include intensive therapist involvment to generalize neurocognitive change to
community functioning. Expert commentary: Compared to other widely implemented
treatments for schizophrenia, cognitive remediation produces better effects on
outcome measures. It is time for cognitive remediation to be adopted as a best
practice in the treatment of schizophrenia.
PMID- 28511563
TI - Authors' response: development and validation of a questionnaire to evaluate
infection control in oral radiology-consistent statistical analyses and
methodology.
PMID- 28511564
TI - Head and neck effective dose and quantitative assessment of image quality: a
study to compare cone beam CT and multislice spiral CT.
AB - OBJECTIVES: To evaluate the effective dose and image quality of horizontal CBCT
in comparison with multislice spiral CT (MSCT) in scans of the head, cervical
spine, ear and dental arches. METHODS: A head and neck Alderson-Rando(r) phantom
(The Phantom Laboratory, Salem, NY) equipped with 74 thermoluminescence
dosemeters was exposed according to 5 different scans in CBCT and 4 different
scans in MSCT. Spatial and contrast resolutions, in terms of modulation transfer
function and contrast-to-noise ratio (CNR), were measured to obtain a
quantitative assessment of image quality. RESULTS: The CBCT effective dose was
248, 249, 361, 565 and 688 uSv in the cervical spine, head, ear, dental arches
with small field of view and dental arches with medium field of view,
respectively. The MSCT effective dose was 3409, 1892, 660 and 812 uSv in the
cervical spine, head, ear and dental arches, respectively. The modulation
transfer function was 0.895 vs 0.347, 0.895 vs 0.275, 0.875 vs 0.342 and 0.961 vs
0.352 for CBCT vs MSCT in the cervical spine, head, ear and dental arches,
respectively. Head and cervical spine MSCT showed greater CNR than CBCT, whereas
CNR of the ear and dental arches showed comparable values. CONCLUSIONS: CBCT was
preferable to MSCT for the ear and dental arches volumetric imaging due to its
lower radiation dose and significantly higher spatial resolution. In the case of
cervical spine and head imaging, MSCT should be generally recommended if a high
contrast resolution is required, despite the greater radiation exposure.
PMID- 28511565
TI - The role of membrane transporters in ovarian cancer chemoresistance and
prognosis.
AB - INTRODUCTION: Ovarian cancer has the highest mortality rate of all cancers in
women. There is currently no effective method for early diagnosis, limiting the
precision of clinical expectations. Predictions of therapeutic efficacy are
currently not available either. Specifically, the development of chemoresistance
against conventional chemotherapy poses a fundamental complication. Some membrane
transporters have been reported to influence chemoresistance, which is often
associated with a poor prognosis. Areas covered: The aim of this article is to
review the existing information about membrane transporters and their role in
both ovarian cancer chemoresistance and its outcomes. We then highlight
limitations of current methodologies and suggest alternatives providing avenues
for future research. Expert opinion: Membrane transporters play an important role
in development of chemoresistance and affect prognosis of ovarian cancer
patients; however, due to variations in methodology and in patient populations,
their specific roles have yet to be clarified. For further evaluation of the
clinical utility of membrane transporters, it is essential to validate results
and improve methods for marker assessment across laboratories. A promising area
for future research is to identify the genetic variability in potential markers
in peripheral blood. These markers would then stratify patients into defined
groups for optimal intervention.
PMID- 28511567
TI - Treating the chronic-phase chronic myeloid leukemia patient: which TKI, when to
switch and when to stop?
AB - INTRODUCTION: With the discovery of imatinib mesylate nearly 20 years ago,
tyrosine kinase inhibitors (TKIs) were found to be effective in chronic myeloid
leukemia (CML). TKI therapy has since revolutionized the treatment of CML and has
served as a paradigm of success for targeted drug therapy in cancer. Several new
TKIs for CML have been approved over the last two decades that exhibit improved
potency over imatinib and have different off-target profiles, providing options
for individualized therapy selection. Areas covered: Current management of
chronic phase CML, including guidance on the sequential use of imatinib and newer
generation TKIs and evolving treatment strategies such as TKI discontinuation.
Relevant literature was identified by searching biomedical databases (i.e.
PubMed) for primary research material. Expert commentary: Although survival
outcomes have drastically improved for CML patients, treatment for CML has grown
more complex with the introduction of next-generation TKIs and the advent of
treatment-free remissions (TFR). Goals of therapy have shifted accordingly, with
increased focus on improving quality of life, managing patient expectations and
optimizing patient adherence.
PMID- 28511566
TI - Polar steroid derivatives from the Vietnamese starfish Astropecten polyacanthus.
AB - Five polar steroid derivatives, including one new glycosylated polyhydroxysteroid
namely polyacanthoside A (1), were isolated from the water-soluble materials from
the MeOH extract of the Vietnamese starfish Astropecten polyacanthus using
various chromatographic separations. The structure elucidation was confirmed by
spectroscopic experiments such as HR-ESI-MS, 1D and 2D NMR. Among the isolated
compounds, (20R,24S)-3beta,6alpha,8,15beta,24-pentahydroxy-5alpha-cholestane (3)
showed significant cytotoxic effect against five human cancer cell lines as
HepG2, KB, LNCaP, MCF7 and SK-Mel2 with the IC50 values from 18.03 +/- 2.63 to
21.59 +/- 3.23 MUM.
PMID- 28511568
TI - Flexor Tendon Ruptures After Distal Scaphoid Excision for Scaphotrapeziotrapezoid
Osteoarthritis.
AB - BACKGROUND: Distal scaphoid excision is one treatment option for osteoarthritis
of the scaphotrapeziotrapezoid (STT) joint following failure of conservative
measures. Potential complications of this procedure include injury to the carpal
ligaments, cartilage, and radial artery. METHODS: A single case was identified by
the senior author, and the medical record was reviewed for surgical notes,
progress notes, and radiographs. RESULTS: A 68-year-old male sustained ruptures
of the flexor digitorum superficialis (FDS) and flexor digitorum profundus to the
index finger 3 years following a distal scaphoid excision for symptomatic STT
osteoarthritis. He required a flexor tendon reconstruction using the remaining
FDS tendon for graft incorporated with a Pulvertaft weave. His midcarpal pain
continued after recovery of his index finger function, eventually requiring a 4
corner fusion of the wrist. CONCLUSIONS: Flexor tendon rupture is a previously
unreported complication of distal scaphoid excision for STT arthritis.
PMID- 28511569
TI - Weightbearing vs Gravity Stress Radiographs for Stability Evaluation of
Supination-External Rotation Fractures of the Ankle.
AB - BACKGROUND: Isolated lateral malleolar fractures may result from a supination
external rotation (SER) injury of the ankle. Stable fractures maintain tibiotalar
congruence due to competent medial restraints and can be treated nonoperatively
with excellent functional results and long-term prognosis. Stability might be
assessed with either stress radiographs or weightbearing radiographs. METHODS: A
consecutive series of patients with closed SER fractures (presumed AO 44-B1) were
prospectively enrolled from 2008 to 2015. Patients with clearly unstable
fractures (medial clear space more than 7 mm) on the initial nonweightbearing
radiograph were excluded and operated on. All other patients were examined with a
gravity stress and a weightbearing anteroposterior radiograph. Borderline
instability of the fracture was assumed when the medial clear space was 4 to 7
mm. Those were treated nonoperatively. RESULTS: Of 104 patients with isolated
lateral malleolar fractures of the SER type, 14 patients were treated operatively
because of clear instability (displacement) on the initial radiographs. Of the
nonoperative patients, 44 patients demonstrated borderline instability on the
gravity stress but stability on the weightbearing radiograph ("gravity
borderline"); the remaining 46 were stable in both tests ("gravity stable"). At
an average follow-up of 23 months, no significant differences were seen in the
American Orthopaedic Foot & Ankle Society hindfoot score (92 points gravity
borderline group vs 93 points gravity-unstable group), the Foot Functional Index
score (11 vs 10 points), the Short Form 36 (SF-36) physical component (86 vs 85
points), and SF-36 mental component (84 vs 81 points). Radiographically, all
fractures had healed with anatomic congruity of the ankle. CONCLUSION:
Weightbearing radiographs provided a reliable basis to decide about stability and
nonoperative treatment in isolated lateral malleolar fractures of the SER type
with excellent clinical and radiographic outcome at short-term follow-up. Gravity
stress radiographs appear to overrate the need for operative treatment. LEVEL OF
EVIDENCE: Level III, prospective comparative study.
PMID- 28511570
TI - Carpal Tunnel Syndrome Following Corrective Osteotomy for Distal Radius Malunion:
A Rare Case Report and Review of the Literature.
AB - BACKGROUND: Although median nerve neuropathy and carpal tunnel syndrome (CTS) are
known complications of both untreated and acutely treated distal radius fracture,
median neuropathy after correction of distal radius malunion is not commonly
reported in hand surgery literature. We describe a patient with severe CTS after
corrective osteotomy, open reduction internal fixation (ORIF) with a volar
locking plate (VLP), and bone grafting for distal radius malunion. METHODS: We
report a case of severe acute CTS as a complication of corrective osteotomy with
bone grafting for distal radius malunion. RESULTS: The patient was treated with
surgical exploration of the median nerve and carpal tunnel release. CONCLUSION:
The authors report a case of acute CTS after ORIF with VLP for a distal radius
malunion warranting surgical exploration and carpal tunnel release. Treatment
teams must be aware of this potential complication so that the threshold for
reoperation is low and irreversible damage to the median nerve is prevented.
PMID- 28511571
TI - Brain Injury and Offending: The Development and Field Testing of a Linkworker
Intervention.
AB - Evidence suggests that traumatic brain injury (TBI) is more prevalent amongst
offender populations than in the general population, and that it can lead to
aggressive behaviour while in custody and impair engagement with offender
rehabilitation programmes. The aim of this study was to develop, implement, and
evaluate a brain injury Linkworker approach designed to support prisoners who
report a significant TBI or multiple mild TBIs. Three clinical case examples are
reported to illustrate the conceptual foundations of the approach and to
demonstrate the feasibility of the service. Early results showed that engagement
with a Linkworker led to effective identification of key areas of intervention
and resulted in better integration for prisoners while in custody and in
enhancement of the outcomes of offender rehabilitation. These initial findings
provide justification for wider implementation and systematic evaluation of the
efficacy of this model of service.
PMID- 28511573
TI - Inhibition of PKR ameliorates lipopolysaccharide-induced acute lung injury by
suppressing NF-kappaB pathway in mice.
AB - Acute lung injury (ALI) is characterized by dramatic lung inflammation and
alveolar epithelial cell death. Although protein kinase R (PKR) (double-stranded
RNA-activated serine/threonine kinase) has been implicated in inflammatory
response to bacterial cell wall components, whether it plays roles in
lipopolysaccharide (LPS)-induced ALI remains unclear. This study was aimed to
reveal whether and how PKR was involved in LPS-induced ALI pathology and the
potential effects of its specific inhibitor, C16 (C13H8N4OS). During the
experiment, mice received C16 (100 or 500 ug/kg) intraperitoneally 1 h before
intratracheal LPS instillation. Then, whole lung lavage was collected for
analysis of total protein levels and proinflammatory cytokines, including tumor
necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and IL-6. The
lungs were tested for Western blot, transferase-mediated dUTP nick-end labeling
(TUNEL) stain and immunohistochemistry. Results showed that PKR phosphorylation
increased significantly after LPS instillation. Furthermore, PKR specific
inhibition attenuated LPS-induced lung injury (hematoxylin and eosin stain),
reduced lung protein permeability (total protein levels in whole lung lavage) and
suppressed proinflammatory cytokines (TNF-alpha, IL-1beta and IL-6) and lung
apoptosis (TUNEL stain and caspase3 activation). Moreover, mechanism-study showed
that C16 significantly suppressed I kappa B kinase (IKK)/I kappa B alpha
(IkappaBalpha)/NF-kappaB signaling pathway after LPS challenge. These findings
suggested that PKR inhibition ameliorated LPS-induced lung inflammation and
apoptosis in mice by suppressing NF-kappaB signaling pathway.
PMID- 28511574
TI - Effects of age and sex on voice onset time: Evidence from Mandarin voiceless
stops.
AB - Considerable studies have addressed effects of age and sex on voice onset time
(VOT) in English. However, few studies have examined these effects on Mandarin
stops. This study attempts to examine effects of age and sex on VOT in Mandarin.
A total of 85 Mandarin-speaking children, aged 4-18 years old, and 13 adults as
reference participated in a production experiment. Productions were elicited by
reading target words in carrier phrases. Results showed that children aged 6-7
years old had longer VOTs than older ones for highly aspirated stops, and the
same tendency was not observed for unaspirated stops. However, no linear
developmental trend was observed for both highly aspirated and unaspirated stops.
In addition, females displayed longer VOTs for highly aspirated stops and shorter
for unaspirated stops, whereas significant sex differences in VOTs existed from
14 years old to adulthood for highly aspirated stops, and no significant sex
differences in VOTs were found for unaspirated stops in each group, indicating
that sex differences in VOTs varied with age and aspiration. The findings suggest
that physiological changes in and differences between males and females provide
account for some, but not all differences in VOTs across age and sex.
PMID- 28511575
TI - Liver Transplantation for Non-Alcoholic Steatohepatitis Related Cirrhosis.
PMID- 28511572
TI - mTOR drives cerebral blood flow and memory deficits in LDLR-/- mice modeling
atherosclerosis and vascular cognitive impairment.
AB - We recently showed that mTOR attenuation blocks progression and abrogates
established cognitive deficits in Alzheimer's disease (AD) mouse models. These
outcomes were associated with the restoration of cerebral blood flow (CBF) and
brain vascular density (BVD) resulting from relief of mTOR inhibition of NO
release. Recent reports suggested a role of mTOR in atherosclerosis. Because mTOR
drives aging and vascular dysfunction is a universal feature of aging, we
hypothesized that mTOR may contribute to brain vascular and cognitive dysfunction
associated with atherosclerosis. We measured CBF, BVD, cognitive function,
markers of inflammation, and parameters of cardiovascular disease in LDLR-/- mice
fed maintenance or high-fat diet +/- rapamycin. Cardiovascular pathologies were
proportional to severity of brain vascular dysfunction. Aortic atheromas were
reduced, CBF and BVD were restored, and cognitive dysfunction was attenuated
potentially through reduction in systemic and brain inflammation following
chronic mTOR attenuation. Our studies suggest that mTOR regulates vascular
integrity and function and that mTOR attenuation may restore neurovascular
function and cardiovascular health. Together with our previous studies in AD
models, our data suggest mTOR-driven vascular damage may be a mechanism shared by
age-associated neurological diseases. Therefore, mTOR attenuation may have
promise for treatment of cognitive impairment in atherosclerosis.
PMID- 28511576
TI - Performance of a Brazilian sample on the Portuguese translation of the BNI Screen
for Higher Cerebral Functions.
AB - INTRODUCTION: The Barrow Neurological Institute (BNI) Screen for Higher Cerebral
Functions (BNIS) has been translated into several languages and found useful in
evaluating multiple domains of cognitive and affective dysfunction, particularly
in neuro-rehabilitation settings. Normative data from countries with high
literacy rates have reported strikingly similar mean level of performance scores
on this test, with age typically correlating higher with total score performance
than education. In the present study, we obtain convenience sample normative data
from a native Brazilian population on a Portuguese translation of the BNIS (i.e.,
BNIS-PT). METHOD: The BNIS was translated into Portuguese by two native speaking
Portuguese neuropsychologists who were also fluent in English. It was then
administered to 201 normally functioning native Brazilian individuals who varied
considerably in age and formal educational training. RESULTS: The mean BNIS total
score was similar to what previous studies reported, but primarily in younger
adults with at least 12 years of formal education. In this Brazilian sample, the
correlation of educational level and BNIS total score was r = .68, p < .001. The
correlation of age and BNIS total score was r = -.36, p < .001. This is the
opposite pattern to that observed in previous standardization studies. The strong
correlation of education with performance in various subtests was observed in all
age groups (ages ranging from 15 to 85 years). CONCLUSION: This standardization
study provides guidelines for calculating expected average performance levels on
the BNIS-PT for Brazilian individuals with varying degrees of age and education.
Educational level positively correlated with test performance on the BNIS-PT and
was repeatedly observed to overshadow the effects of age, suggesting its
important role in the development of higher cerebral functions in multiple
domains in a Brazilian sample of normally functioning individuals.
PMID- 28511577
TI - Sonographic assessment of the lower uterine segment during active labor in women
with or without a uterine scar - a prospective study.
AB - OBJECTIVES: No study thus far has evaluated the LUS thickness in active labor. In
this study, we endeavored to assess the LUS during active labor. METHODS: Using
transabdominal sonography in the mid-sagittal position with a full urinary
bladder, the thickness of the LUS was measured during active labor phase in women
with or without a history of a previous cesarean section. RESULTS: A total of 28
women with a previous cesarean delivery were compared to 29 women without a
history of uterine surgery. The median LUS was significantly thinner in women
with a uterine scar both during (4 versus 5 mm, p = .001) and between
contractions (5 versus 7 mm, p = .011). Paired comparison of LUS thickness
between and during contractions within each group showed that thinning of LUS
during contraction was significant for both the previous CS group (p < .001) and
the control group (p < .001). We found no correlation between LUS thickness and
chances of successful TOLAC. CONCLUSIONS: In this study, we characterized for the
first time the LUS during active labor. We found that LUS was significantly
thinner in women after a previous CS and that the LUS was significantly thinner
during contraction.
PMID- 28511579
TI - Does an attention bias to appetitive and aversive words modulate interference
control in youth with ADHD?
AB - Interference control refers to the ability to selectively attend to certain
information while ignoring distracting information. This ability can vary as a
function of distractor relevance. Distractors that are particularly relevant to
an individual may attract more attention than less relevant distractors. This is
referred to as attention bias. Weak interference control and altered reward
sensitivity are both important features of attention deficit hyperactivity
disorder (ADHD). However, interference control is typically studied in isolation.
This study integrates both. Youths (aged 9 to 17 years) with ADHD (n = 37, 25
boys) and typically-developing controls (n = 38, 20 boys) completed a Stroop task
using appetitive words and matched neutral words to assess whether appetitive
distractors diminished interference control more in youths with ADHD than
controls. In order to test for specificity, aversive words were also included. As
expected, appetitive words disrupted interference control but this effect was not
stronger for youths with ADHD than the controls. Aversive words, on the other
hand, facilitated interference control. Dimensional analyses revealed that this
facilitation effect increased substantially as a function of ADHD symptom
severity. Possible mechanisms for this effect include up-regulation of
interference control as a function of induced negative mood, or as a function of
increased effort. In conclusion, appetitive words do not lead to worse
interference control in youths with ADHD compared with controls. Interference
control was modulated in a valence-specific manner, concurrent with mood-induced
effects on cognitive control.
PMID- 28511578
TI - Retinal atrophy in relation to visual functioning and vision-related quality of
life in patients with multiple sclerosis.
AB - BACKGROUND: Inner retinal layer atrophy in patients with multiple sclerosis (MS)
has been validated as a structural imaging biomarker for neurodegeneration.
OBJECTIVE: To determine how retinal layer thickness relates to high-contrast
visual acuity (HCVA), low-contrast visual acuity (LCVA) and vision-related
quality of life (QoL) and to investigate the effect of previous episodes on MS
associated optic neuritis (MSON). METHODS: Spectral-domain optical coherence
tomography (SD-OCT) was performed in 267 patients with MS. Images were segmented
for the peripapillary retinal nerve fiber layer (pRNFL) and the macular ganglion
cell inner plexiform layer (GCIPL). Ophthalmological evaluations included history
of MSON, HCVA, LCVA, and vision-related QoL. RESULTS: Independent of MSON, HCVA
and LCVA were significantly associated with pRNFL and GCIPL thicknesses. Vision
related QoL was positively associated with pRNFL (beta = 0.92, p = 0.06) and
GCIPL (beta = 0.93, p = 0.02) thicknesses. These associations were independent of
MSON. Not only binocular but also monocular atrophy of the inner retinal layers
was associated with lower vision-related QoL. CONCLUSION: This study showed that
retinal atrophy has a significant impact on visual functioning in patients with
MS. OCT may therefore provide useful insight to patients with visual dysfunction,
and our findings support including OCT and vision-related QoL measures into optic
neuritis treatment trials.
PMID- 28511580
TI - Deleterious Effects From Occupational Exposure to Ethylene Thiourea in Pregnant
Women.
AB - Human exposure to endocrine disrupting chemicals (EDCs) has become common as a
result of widespread application of these chemicals to the food supply,
environmental contamination, and occupational exposures (Caserta et al., 2011).
However, relatively little is known about the effects of EDCs such as ethylene
thiourea (ETU) in developing fetuses and the lasting implications of this
disruption on human development from birth through adulthood. Of highest concern
are chronic, low-dose exposures among industrial and agricultural workers.
Current knowledge regarding the significance of endocrine thyroid signaling on
normal human development raises serious concerns about the possible deleterious
effects of EDCs in the developing fetus, children, and mature adults.
Occupational health nurses are critical in identifying women and families at
increased risk of ETU exposure and mitigating early exposures in pregnancy.
PMID- 28511581
TI - The RANZCP guidelines for Schizophrenia: Why is our practice so far short of our
recommendations, and what can we do about it?
AB - The new RANZCP guidelines for the treatment of schizophrenia and related
disorders highlights what we know works. In this paper, we examine why patients
so often fail to benefit from this knowledge and why clinical practice falls so
far short of the recommended standard. Instead of the continuous improvement that
we expect of health care in general, in psychiatry we face an accelerating
decline in systems of care. There has been a sustained underinvestment in public
mental health care and a shared failure by State and Federal governments to
construct and commit to a governance and funding model that can deliver the
standard of care that is available in other major non-communicable diseases, and
which we know is equally possible for severe mental illness. This paper sets out
some of the reasons for the poor quality of care received by many people with
schizophrenia and related disorders in Australia, and describes ways that care
could be improved. In particular, we recommend an explicit statement of what
constitutes an adequate standard of care, for people at all stages of these
illnesses. This would help provide transparency about whether the care provided
by mental health services achieves these benchmarks, and enable publication of
results comparing the performance of different states and regional services.
Patients and families, as well as professional, consumer and carer organizations
would then be able to see clearly where the deficits are and demand resources and
care that match the recommendations.
PMID- 28511582
TI - Evaluation of an Unfractionated Heparin Pharmacy Dosing Protocol for the
Treatment of Venous Thromboembolism in Nonobese, Obese, and Severely Obese
Patients.
AB - BACKGROUND: Despite large interpatient variability in dose response, heparin is
utilized for treatment of venous thromboembolism (VTE). Current data on the
optimal heparin dosing in obese patients are conflicting. OBJECTIVE: The
objective was to evaluate the time and dose required to achieve a therapeutic
activated partial thromboplastin time (aPTT) in nonobese, obese, and severely
obese patients using a pharmacist-directed heparin dosing protocol. METHODS: This
was a retrospective cohort study in a single-center community hospital inpatient
setting. Adult patients receiving heparin for VTE treatment from July 1, 2013, to
July 31, 2015, were evaluated. Patients were categorized into 3 groups: nonobese
(BMI < 30 kg/m2), obese (BMI = 30-39.9 kg/m2), and severely obese (BMI >= 40
kg/m2). Data on height, weight, initial bolus dose, initial infusion rate, time
to therapeutic aPTT, and therapeutic infusion rate were collected. Dosing body
weight (DBW) was utilized for patients 20% over their ideal body weight (IBW).
The primary outcome was time to therapeutic aPTT. RESULTS: Analysis included 298
patients. Median times to therapeutic aPTT (hours:minutes) in the nonobese,
obese, and severely obese were 15:00 (interquartile range [IQR] = 8:05-23:21),
15:40 (IQR = 9:22-25:10), and 15:22 (IQR = 7.54-23:40), respectively ( P =
0.506). There was no difference in bleeding among the nonobese (14%), obese
(13.9%), or severely obese groups (7.9%; P = 0.453). No adverse thrombotic events
occurred during hospitalization. CONCLUSION: Using a DBW for heparin dosing in
patients 20% over their IBW resulted in similar times to therapeutic aPTT and
adverse events in the nonobese, obese, and severely obese.
PMID- 28511583
TI - Deciphering the crucial residues involved in heterodimerization of Bak peptide
and anti-apoptotic proteins for apoptosis.
AB - B-cell lymphoma 2 (Bcl-2) family proteins are the central regulators of
apoptosis, functioning via mitochondrial outer membrane permeabilization. The
family members are involved in several stages of apoptosis regulation. The
overexpression of the anti-apoptotic proteins leads to several cancer
pathological conditions. This overexpression is modulated or inhibited by
heterodimerization of pro-apoptotic BH3 domain or BH3-only peptides to the
hydrophobic groove present at the surface of anti-apoptotic proteins.
Additionally, the heterodimerization displayed differences in binding affinity
profile among the pro-apoptotic peptides binding to anti-apoptotic proteins. In
light of discovering the novel peptide/drug molecules that contain the potential
to inhibit specific anti-apoptotic protein, it is necessary to understand the
molecular basis of recognition between the protein and its binding partner
(peptide or ligand) along with its binding energies. Therefore, the present work
focused on deciphering the molecular basis of recognition between pro-apoptotic
Bak peptide binding to different anti-apoptotic (Bcl-xL, Bfl-1, Bcl-W, Mcl-1, and
Bcl-2) proteins using advanced Molecular Dynamics (MD) approach such as Molecular
Mechanics-Generalized Born Solvent Accessible. The results from our investigation
revealed that the predicted binding free energies showed excellent correlation
with the experimental values (r2 = .95). The electrostatic (DeltaGele)
contributions are the major component that drives the interaction between Bak
peptides and different anti-apoptotic peptides. Additionally, van der Waals
(DeltaGvdw) energies also play an indispensible role in determining the binding
free energy. Furthermore, the decomposition analysis highlighted the
comprehensive information about the energy contributions of hotspot residues
involved in stabilizing the interaction between Bak peptide and different anti
apoptotic proteins.
PMID- 28511584
TI - A Pilot Intervention Designed to Address Behavioral Factors That Place
Overweight/Obese Young Children at Risk for Later-Life Obesity.
AB - The purpose of this pilot randomized controlled trial (RCT) was to intervene with
parents of overweight/obese 4- to 8-year-old children to improve child
internalizing and externalizing behaviors. Parent-child dyads ( N = 60) were
randomly assigned to treatment or comparison conditions. Parents attended four
intervention sessions at their child's primary health care office over 3 months.
Child behaviors were assessed at 0, 3, 6, and 12 months post intervention.
Parental beliefs in their skills/abilities increased in the experimental group
parents, but there was no statistical difference between groups at any time.
Child externalizing behaviors significantly decreased from baseline to
postintervention for both groups ( F = 3.26, p = .020). Post hoc model testing
suggests that this change was more pronounced in the intervention group ( F =
0.56, p = .692). Child somatic symptoms significantly decreased over time ( F =
4.55, p = .004), and there were group differences in child depressive behaviors (
F = 6.19, p = .020). These findings suggest that a parent-focused intervention
program demonstrated positive preliminary effects on children's behaviors.
PMID- 28511585
TI - Three-Phase Adaptive Radiation Therapy for Patients With Nasopharyngeal Carcinoma
Undergoing Intensity-Modulated Radiation Therapy: Dosimetric Analysis.
AB - Patients with nasopharyngeal carcinoma undergoing intensity-modulated radiation
therapy may experience significant anatomic changes throughout the entire
treatment course, and adaptive radiation therapy may be necessary to maintain
optimal dose delivered both to the targets and to the critical structures. The
timing of adaptive radiation therapy, however, is largely unknown. This study was
to evaluate the dosimetric benefits of a 3-phase adaptive radiation therapy
technique for nasopharyngeal carcinoma. Twenty patients with nasopharyngeal
carcinoma treated with intensity-modulated radiation therapy were recruited
prospectively. After fractions 5 and 15, each patient had repeat computed
tomography scans, and adaptive replans with recontouring the targets and organs
at risk on the new computed tomography images were generated and used for
subsequent treatment (replan 1 and replan 2). Two hybrid intensity-modulated
radiation therapy plans (plan 1 and plan 2) were generated by superimposing the
initial plan (plan 0) to each repeated new computed tomography image, reflecting
the actual dose delivered to the targets and organs at risk if no changes were
made to the original plan. Dosimetric comparisons were made between the adaptive
replans (adaptive radiation therapy plans: plan 0 + replan 1 + replan 2) and
their corresponding nonadaptive radiation therapy plans (plan 0 + plan 1 + plan
2). Comparing with the nonadaptive radiation therapy plans, the adaptive
radiation therapy plans resulted in a significant improvement in conformity index
for planning target volumes for primary disease, involved lymph node, high-risk
clinical target volume, and low-risk clinical target volume (PTVnx, PTVnd, PTV1,
and PTV2, respectively). Median V95 for PTVnx; D95, D99, V100, V95, and V93 for
PTVnd; D99 and V100 for PTV1; and D95, D99, V100, V95, and V93 for PTV2 were
increased significantly. There were significant dose-volume reductions, including
maximum doses to the brainstem and temporal lobes, mean doses to the glottis, V50
for the supraglottis, Dmean and V30 for the left parotid, median dose to the
right optic nerve, and V55 for the skin. The 3-phase adaptive intensity-modulated
radiation therapy for patients with nasopharyngeal carcinoma results in
improvements in target coverage and conformity index and decreased doses to some
organs at risk.
PMID- 28511586
TI - Bioprocess optimization of PHB homopolymer and copolymer P3 (HB-co-HV) by
Acinetobacter junii BP25 utilizing rice mill effluent as sustainable substrate.
AB - The potential use of parboiled rice mill effluent as a cheap substrate for the
production of homopolymer and copolymer of Polyhydroxyalkanoates (PHAs) by
Acinetobacter junii BP 25 was investigated for the first time. Process
optimization by one factor at a time led to homopolymer polyhydroxybutyrate (PHB)
production of 2.64 +/- 0.18 g/l with 94.28% PHB content using a two-stage batch
cultivation mode. BP 25 furthermore produced polyhydroxybutyrate-co
hydroxyvalerate (P3 (HB-co-HV)), with the addition of valeric acid as an additive
to the substrate, yielding (2.56 +/- 0.12 g/l dry biomass, 2.20 +/- 0.15 g/l PHA)
a copolymer content of 85.93%. Thus, rice mill effluent can be an effective and
relatively low-cost alternative for the production of PHA, replacing the pure
substrates.
PMID- 28511588
TI - An evening milk drink can affect word recall in Indonesian children with
decreased sleep efficiency: A randomized controlled trial.
AB - STUDY OBJECTIVES: Sleep is important for memory consolidation in children. This
study intended to find out whether an evening milk-based drink could influence
sleep efficiency and memory recall in a group of Indonesian children (5-6 years
old) with sleep deprivation. METHODS: Children were randomly allocated to one of
three interventions: Reference product, satiety-stimulating product, and a
relaxing product. The intervention lasted for 6 weeks and children consumed two
servings per day of each 200 ml, the serving in the morning being the same for
all children. All measurements took place at baseline and at the end of the
intervention. Sleep parameters were studied using actigraphy and a sleep diary
during three consecutive days. Memory consolidation was tested using a 20 word
pair list, which was memorized the evening before being recalled the next morning
at home-base. Anthropometry was measured using standard equipment. RESULTS: The
Satiety group showed a significant decrease in word recall, and a significant
increase in nocturnal awakenings that was inversely associated with sleep
efficiency at the end of the intervention. Sleep efficiency did not differ
between the three groups being 75.5 +/- 8.6% and 75.7 +/- 6.3% at baseline and
end of the intervention, respectively. Despite the lower energy intake in the
Standard (reference) group, this condition showed the highest increase in weight.
DISCUSSION: Evening growing-up milks can affect memory recall, sleep
characteristics, and growth. However, to correct sleep efficiency and sleep
duration, improvement of parental behavior may be the most important factor with
nutrition providing a supplementary effect.
PMID- 28511590
TI - Temperature Rise in Kirschner Wires Inserted Using Two Drilling Methods: Forward
and Oscillation.
AB - BACKGROUND: Kirschner wires (K-wires) are commonly used in orthopedic surgery.
However, the loosening of the pins can lead to delayed or improper healing or
infection. Wire loosening can occur by thermal necrosis that occurs due to heat
produced during wire insertion. Although the parameters that affect temperature
rise in cortical bone during wire insertion and drilling have been studied, the
effect of drilling mode (oscillation versus forward) is unknown. The purpose of
this study was to compare the temperature changes occurring in cortical bone
during wire insertions by oscillating and forward drills. Our hypothesis is that
oscillation drilling would produce less heat compared with forward drilling in K
wire insertion with 2 commonly used wire diameters. METHODS: We drilled K-wires
in a pig metacarpal model and measured the temperature rise between forward and
oscillation drilling modes using diamond-tipped 0.062- and 0.045-inch-diameter K
wires. There were 20 holes drilled for each group (n = 20). RESULTS: The average
temperature rise using the 0.062-inch K-wire under forward and oscillation
insertion was 14.0 +/- 5.5 degrees C and 8.8 +/- 2.6 degrees C, respectively. For
the 0.045-inch K-wire, under forward and oscillation insertion, the average
temperature rise was 11.4 +/- 2.6 degrees C and 7.1 +/- 1.9 degrees C,
respectively. The effects of the drilling mode and wire diameter on temperature
rise were significant ( P < .05). CONCLUSIONS: In conclusion, the oscillation of
K-wires during insertion causes a lower temperature rise when compared with
forward drilling.
PMID- 28511589
TI - A semi-automatic method for the extraction of the portal venous input function in
quantitative dynamic contrast-enhanced CT of the liver.
AB - OBJECTIVE: To aid the extraction of the portal venous input function (PVIF) from
axial dynamic contrast-enhanced CT images of the liver, eliminating the need for
full manual outlining of the vessel across time points. METHODS: A cohort of 20
patients undergoing perfusion CT imaging of the liver was examined. Dynamic
images of the liver were reformatted into contiguous thin slices. A region of
interest was defined within a transverse section of the portal vein on a single
contrast-enhanced image. This region of interest was then computationally
projected across all thin slices for all time points to yield a semi-automated
PVIF curve. This was compared against the "gold-standard" PVIF curve obtained by
conventional manual outlining. RESULTS: Bland-Altman plots of curve
characteristics indicated no substantial difference between automated and manual
PVIF curves [concordance correlation coefficient in the range (0.66, 0.98)]. No
substantial differences were shown by Bland-Altman plots of derived
pharmacokinetic parameters when a suitable kinetic model was applied in each case
[concordance correlation coefficient in range (0.92, 0.95)]. CONCLUSION: This
semi-automated method of extracting the PVIF performed equivalently to a "gold
standard" manual method for assessing liver function. Advances in knowledge: This
technique provides a quick, simple and effective solution to the problems
incurred by respiration motion and partial volume factors in the determination of
the PVIF in liver dynamic contrast-enhanced CT.
PMID- 28511591
TI - Psychometric evaluation of the Signs of Depression Scale with a revised scoring
mechanism in stroke patients with communicative impairment.
AB - OBJECTIVES: To investigate (1) the diagnostic value of the Signs of Depression
Scale (SODS) in a Likert scale format and (2) whether the Likert scale improves
the diagnostic value compared with the original dichotomous scale. DESIGN: Cross
sectional multicentre study. SETTING: One general and one university hospital in
the Netherlands. SUBJECTS: A total of 116 consecutive hospitalized stroke
patients, of whom 53 were patients with communicative impairment. MAIN MEASURES:
Depression was diagnosed with the Composite International Diagnostic Interview
(CIDI) administered to the patients' relatives. The Barthel Index (BI) was used
as an external validator. RESULTS: The correlation between the CIDI and the SODS
Likert or the SODS was small ( rb = 0.18), and the correlation between the
Barthel Index and the SODS-Likert ( rs = -0.30) or the SODS ( rs = -0.33) was
moderate. For both instruments, the discriminatory power for diagnosing
depression when compared with the CIDI was best at a cut-off score of ?2. The
internal consistency of the SODS-Likert was acceptable (alpha = 0.69) and
slightly higher than that of the SODS (alpha = 0.57). The inter-rater reliability
of the SODS-Likert and the SODS was acceptable (intraclass correlation
coefficient (ICC) 0.66 and ICC 0.80, respectively). The clinical utility was
rated good. CONCLUSION: The diagnostic value of the SODS did not improve using a
Likert scale format. However, the diagnostic value of the original dichotomous
SODS is reasonable for the initial mood assessment of stroke patients with
communicative impairment.
PMID- 28511592
TI - Cytotoxicity, mutagenicity, and antimutagenicity of the gentisic acid on HTC
cells.
AB - Gentisic acid (GA) exhibits antioxidant, anti-inflammatory, and antibiotic
activities. This substance can be found in citrus fruits, grapes, olive oil, and
peas. Considering that there are few studies in the literature on the toxicity of
GA, the present work aimed to investigate its cytotoxic, mutagenic, and
antimutagenic activities on HTC cells. GA was diluted in culture medium at the
final concentration of 0.08, 0.16, 0.8, 1.6, and 8 MUg/mL. The cytotoxicity was
determined by the MTT assay and Trypan Blue exclusion method, with methyl
methanesulfonate and doxorubicin as positive controls, respectively. The
cytokinesis-block micronucleus assay determined the mutagenic/antimutagenic
activity with benzo[a]pyrene as positive control. Negative control received
culture medium only. GA (0.08-8 MUg/mL) was not cytotoxic to HTC cells by the MTT
assay nor the Trypan Blue exclusion method as no statistical difference was
observed when compared to the control. Concentration of 0.08 and 0.8 MUg/mL
showed no mutagenic or clastogenic effects, as no significant micronuclei
inductions were observed, different from 8 MUg/mL, that was mutagenic.
Furthermore, none of the concentrations presented an antiproliferative activity.
The antimutagenic activity of GA (0.08 MUg/mL) was observed at the simultaneous
treatment, as it reduced the frequency of micronuclei by 76% (24 h) and 79% (48
h). Although pre- and post-treatments were not statistically different from the
mutagen, they reduced the induced-damage by 11% and 21%, respectively. The
present study indicated the absence of cytotoxicity and antiproliferative
activities of GA, in addition to their antimutagenic/protective effects that may
contribute to human health.
PMID- 28511593
TI - Convergence Insufficiency Identifies Athletes at Risk of Prolonged Recovery From
Sport-Related Concussion.
AB - BACKGROUND: Sensitive and specific screening methods are needed to identify
athletes at risk of prolonged recovery after sport-related concussion (SRC).
Convergence insufficiency (CI) is a common finding in concussed athletes.
PURPOSE: To assess the relationship between CI and recovery after SRC at the
initial office visit. STUDY DESIGN: Case-control study; Level of evidence, 3.
METHODS: In this retrospective cohort study, 270 athletes (147 male, 123 female),
mean +/- SD age 14.7 +/- 2.0 years (range, 10-21 years), with the diagnosis of
SRC who presented for initial office visit between January 2014 and January 2016
were evaluated for near point of convergence (NPC). The athletes were categorized
into 2 groups: normal near point of convergence (NPC <=6 cm), and convergence
insufficiency (NPC >6 cm). These athletes were then followed to determine
recovery time. RESULTS: Athletes presented for initial office visit at a mean of
5.2 +/- 4.2 days (range, 1-21 days) after SRC. Half of the athletes had CI after
SRC (50.4%; n = 136). Athletes with CI (NPC 12.3 +/- 4.7 cm) took significantly
longer to recover after SRC, requiring 51.6 +/- 53.9 days, compared with athletes
with normal NPC (4.1 +/- 1.3 cm), who required 19.2 +/- 14.7 days ( P < .001).
After controlling for potential confounding variables, CI significantly increased
the odds of prolonged recovery (>=28 days from injury) by 12.3-fold ( P < .001;
95% confidence interval, 6.6-23.0). CI screening correctly classified 75.2% of
our sample with 84.2% sensitivity and 70.0% specificity. The positive predictive
value for CI and prolonged recovery was 62.5%, and the negative predictive value
was 88.1%. CONCLUSION: CI at the initial office visit identified athletes at
increased risk of prolonged recovery after SCR. Clinicians should consider
measuring NPC in concussed athletes as a quick and inexpensive prognostic
screening method.
PMID- 28511594
TI - Fixation Strength in Full and Limited Fixation of Osteoporotic Distal Radius
Fractures.
AB - BACKGROUND: The purpose of this investigation is to determine whether
osteoporotic intra-articular distal radius fractures surgically treated by
filling all 7 distal screws of a volar plate will have a higher load to failure
than those treated by filling only 4 distal screws. METHODS: Ten matched pairs of
fresh frozen cadaveric forearms were randomized within each pair to be treated by
using either all 7 of the distal holes of a volar plate or only 4 distal screws.
The distal radius fixation was performed with unicortical screws going to but not
through the dorsal cortex, and the most distal screws were placed within 4 mm of
the joint surface. An AO C2 type fracture was then created. All specimens were
tested cyclically, with an axial load of 60 N, at 3 Hz for 1000 cycles to
simulate early postoperative motion. All specimens were subsequently tested to
mechanical failure. RESULTS: There were no failures in either group during cyclic
testing. There was no difference detected between groups for mean stiffness,
yield load, peak load, or load to clinical failure. In both groups, the yield
load, peak load, and load to clinical failure were higher than the 60- to 100-N
forces encountered during postoperative rehabilitation. CONCLUSIONS: There was no
difference detected between osteoporotic intra-articular distal radius fractures
treated by utilizing all 7 of the distal screws of a volar plate compared with
those treated with only 4 distal screws.
PMID- 28511595
TI - Presence and Predictive Value of Obsessive-Compulsive Symptoms in Anxiety and
Depressive Disorders.
AB - OBJECTIVE: Obsessive-compulsive symptoms (OCS) co-occur frequently with anxiety
and depressive disorders, but the nature of their relationship and their impact
on severity of anxiety and depressive disorders is poorly understood. In a large
sample of patients with anxiety and depressive disorders, we assessed the
frequency of OCS, defined as a Young Adult Self-Report Scale-obsessive-compulsive
symptoms score >7. The associations between OCS and severity of anxiety and/or
depressive disorders were examined, and it was investigated whether OCS predict
onset, relapse, and persistence of anxiety and depressive disorders. METHODS:
Data were obtained from the third (at 2-year follow-up) and fourth wave (at 4
year follow-up) of data collection in the Netherlands Study of Anxiety and
Depression cohort, including 469 healthy controls, 909 participants with a
remitted disorder, and 747 participants with a current anxiety and/or depressive
disorder. RESULTS: OCS were present in 23.6% of the total sample, most notably in
those with current combined anxiety and depressive disorders. In patients with a
current disorder, OCS were associated with severity of this disorder. Moreover,
OCS predicted (1) first onset of anxiety and/or depressive disorders in healthy
controls (odds ratio [OR], 5.79; 95% confidence interval [CI], 1.15 to 29.14),
(2) relapse in those with remitted anxiety and/or depressive disorders (OR, 2.31;
95% CI, 1.55 to 3.46), and (3) persistence in patients with the combination of
current anxiety and depressive disorders (OR, 4.42; 95% CI, 2.54 to 7.70) within
the 2-year follow-up period Conclusions: OCS are closely related to both the
presence and severity of anxiety and depressive disorders and affect their course
trajectories. Hence, OCS might be regarded as a course specifier signaling
unfavorable outcomes. This specifier may be useful in clinical care to adapt and
intensify treatment in individual patients.
PMID- 28511597
TI - Understanding sleep-wake mechanisms and drug discovery.
AB - INTRODUCTION: Although not discernible at first glance, sleep is a highly active
and regulated brain state. Although we spend practically one third of our
lifetimes in this stage, its importance is often taken for granted. Sleep loss
can lead to disease, error and economic loss. Our understanding of how sleep is
achieved has greatly advanced in recent years, and with that, the management of
sleep disorders has improved. There is still room for improvement and recently
many new compounds have reached clinical trials with a few being approved for
commercial use. Areas covered: In this review, the authors make the case of sleep
disorders as a matter of public health. The mechanisms of sleep transition are
discussed emphasizing the wake and sleep promoting interaction of different brain
regions. Finally, advances in pharmacotherapy are examined in the context of
chronic insomnia and narcolepsy. Expert opinion: The orexinergic system is an
example of a breakthrough in sleep medicine that has catalyzed drug development.
Nevertheless, sleep is a topic still with many unanswered questions. That being
said, the melanin-concentrating hormone system is becoming increasingly relevant
and we speculate it will be the next target of sleep medication.
PMID- 28511598
TI - Silexan in anxiety disorders: Clinical data and pharmacological background.
AB - OBJECTIVES: Silexan is a lavender oil preparation available in 80-mg capsules.
Here we review clinical trials investigating its anxiolytic efficacy, safety and
tolerability in humans, as well as preclinical investigations supporting this
therapeutic use. METHODS: Besides three selected publications reporting
preclinical investigations, seven clinical trials are included, of which five had
a treatment duration of 6 or 10 weeks. Primary outcome measure was the HAM-A
total score reduction, while single items were assessed with regard to effects on
concomitant depressive symptoms and on quality of sleep. RESULTS: In patients
with subthreshold (subsyndromal) anxiety or generalised anxiety disorder (GAD),
an anxiolytic effect of Silexan was evident after 2 weeks. HAM-A total score
reductions between baseline and end of treatment were significantly superior to
placebo in patients with subthreshold anxiety and comparable with those achieved
under lorazepam or paroxetine in patients with GAD. In addition, Silexan had
beneficial effects on typical concomitant symptoms of anxiety disorders, such as
impaired sleep, somatic complaints, co-morbid depression or decreased quality of
life. Except for mild gastrointestinal symptoms, Silexan did not induce any
adverse effects and did not cause drug interactions, sedation or withdrawal
symptoms at daily doses of 80 or 160 mg. CONCLUSIONS: Silexan is a safe and
effective treatment in anxiety disorders.
PMID- 28511599
TI - Teething.
AB - Misconceptions about the teething process has led to high infant morbidity and
mortality, which was recently experienced in Nigeria due to consumption of an
adulterated drug used in the prevention and treatment of teething-related
illnesses in infants. It is however, unknown if these misconceptions still
persist in a rural town in Nigeria despite oral health awareness campaigns
targeted at this. The aim of this study is to assess the beliefs and practices of
residents in Igbo Ora, a rural township in Nigeria, regarding the teething
process. A descriptive cross-sectional study was conducted among 393 adults in
Igbo Ora using a 33-item, semistructured questionnaire. Symptoms such as diarrhea
(80.7%), fever (69.2%), and boils (64.4%) were still considered as a must to
accompany teething. Teething powder, teething syrup, and traditional concoctions
were commonly recommended by (42.0%), (31.6%), and (48.1%) of the respondents,
respectively, to treat and prevent teething symptoms. This study revealed that
misconceptions about teething are still highly prevalent among the populace in
Igbo Ora, and a structured oral health education intervention at the community
level is urgently needed.
PMID- 28511600
TI - Knowledge Attitude and Practices Toward Lassa Fever Control and Prevention Among
Residents of Ile-Ife, Southwest Nigeria.
AB - Lassa fever had been reported as a cause of death especially in endemic parts of
Nigeria. This study assessed the knowledge, attitude, and practices toward Lassa
fever control and prevention among residents of Ile-Ife, southwest Nigeria.
Descriptive cross-sectional study was conducted among consenting randomly
selected adults using an interviewer administered questionnaire. Data were
analyzed using descriptive and inferential statistics. A total of 400
questionnaires with completed data were analyzed (response rate 96%). Majority,
207 (51.8%), were males while 193 (48.2%) were females. Most, 234 (58.5%), had
tertiary education while 148 (37%) had secondary education. Fifty-nine percent
had heard of Lassa fever with radio as their major source of information. About
76% had inadequate knowledge, 54% had negative attitude while 51% had poor
practice toward Lassa fever. Determinants of knowledge of Lassa fever include
having higher education (Adjusted Odd Ratio (AOR) = 11.49, 95% CI [3.10, 42.69],
p = .0001), being in civil service (AOR = 0.22, 95% CI [0.09, 0.51], p = .01),
and earning higher income (AOR = 4.23, 95% CI [2.61, 6.84], p = .0001). In
conclusion, the knowledge, attitude, as well as preventive practices to Lassa
fever were poor. It is necessary to increase public education and improve
hygienic practices.
PMID- 28511601
TI - Satisfaction of Patients Attending Public HIV or AIDS Care and Treatment Centers
in Kinondoni District, Tanzania.
AB - Satisfaction of care and treatment among HIV patients is one of the important
elements for adherence. This study aimed to determine levels of satisfaction and
associated factors among HIV-infected patients attending public care and
treatment centers (CTCs) in Tanzania. The study was cross-sectional using face-to
face interviews. Satisfaction was measured using a total of 30 questions from a
domain of six area of CTC service delivery. To assess independent predictors of
levels of satisfaction, we used multilevel ordinal logistic regression analysis.
We enrolled 434 study participants. Of these, 5% reported low satisfaction, 25%
medium satisfaction, and 70% reported high satisfaction. The CTC environment was
rated low by 56% of the patients. Predictors of levels of satisfaction were age
of patient and health facility level. Low levels of satisfaction with CTC
environment and laboratory services underscore the need for improvement of these
areas.
PMID- 28511602
TI - Evaluation of Student Handwashing Practices During a School-Based Hygiene Program
in Rural Western Kenya, 2007.
AB - Unsafe drinking water and inadequate handwashing facilities in primary schools
increase the risk of absenteeism due to diarrhea and respiratory infections. To
mitigate these risks, we provided 28 schools in rural Western Kenya with
handwashing and drinking water stations (containers with lids and taps on metal
stands), bleach for water treatment, soap for handwashing, and educational
materials. We observed the use of the water stations and assessed teachers'
attitudes toward the intervention. Of 151 total handwashing stations, 69 (59%)
were observed to have soap and water and treated drinking water 4 months after
implementation; observations of pupils showed an increase in handwashing behavior
in water stations located < 10 m, as compared with those >10 m, from latrines ( p
< .02). In focus groups, teachers reported improved cleanliness and decreased
illness in pupils. Teacher training and installation of water stations resulted
in observed improvements in pupils' hygiene, particularly when water stations
were located <10 m from latrines.
PMID- 28511603
TI - Clinical Experience With Perampanel for Refractory Pediatric Epilepsy in One
Canadian Center.
AB - Perampanel (PER) is a new antiseizure medication that inhibits the alpha-amino-3
hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) class of glutamate receptors.
It is important for physicians to be aware of the efficacy and tolerability of
new drugs in the postmarketing phase. We performed a retrospective review of our
experience with perampanel at BC Children's Hospital. Twenty-four pediatric
patients prescribed perampanel from 2014 to 2016 were identified. Fifteen (63%)
discontinued perampanel, and 10 (42%) had greater than 50% reduction in seizures.
Twelve (50%) had behavioral and 8 (33%) had nonbehavioral adverse events. One
third experienced serious adverse events. One patient experienced oculogyric
crisis, which is not previously reported with perampanel. Adverse events were not
dose related and were reversible. Possible risk factors for behavioral adverse
events include a history of behavioral problems with other antiseizure
medications and preexisting behavioral comorbidities. It is important to counsel
patients about the potential for serious adverse events, particularly behavioral,
when prescribing perampanel.
PMID- 28511604
TI - Duplicated or Hybridized Peptide Functional Domains Promote Oral Homeostasis.
AB - Proteins that have existed for millions of years frequently contain repeats of
functional domains within their primary structure, thereby improving their
functional capacity. In the evolutionary young statherin protein contained within
the in vivo-acquired enamel pellicle (AEP), we identified a single functional
domain (DR9) located within the protein N-terminal portion that exhibits a higher
affinity for hydroxyapatite and more efficient protection against enamel
demineralization compared to other native statherin peptides. Thus, we tested the
hypothesis that multiplication of functional domains of naturally occurring
pellicle peptides amplifies protection against enamel demineralization. In
addition, a specific amino acid sequence from histatin 3 (RR-14) was introduced
to the hybrid peptides for further testing. Enamel specimens were sectioned to
150-um thickness and randomly grouped as follows: DR9, DR9-DR9, DR9-RR14,
statherin, histatin 1, or distilled water (control). After submersion for 2 h at
37 degrees C, the specimens were placed in 2 mL demineralization solution for 12
d at 37 degrees C. Upon sample removal, the remaining solution was subjected to
colorimetric assays to determine the amount of calcium and phosphate released
from each specimen. DR9-DR9 amplified protection against enamel demineralization
when compared to single DR9 or statherin. Notably, the hybrid peptide DR9-RR14
demonstrated relatively strong protection when the antimicrobial property of
these peptides was tested against Candida albicans and Streptococcus mutans. DR9
RR14 was able to maintain 50% of the antifungal activity compared with RR14 for
C. albicans and similar values of S. mutans killing activity. This study has
pioneered the functional exploration of the natural peptide constituents of the
AEP and their evolution-inspired engineered peptides. The knowledge obtained here
may provide a basis for the development of stable (proteinase-resistant)
synthetic peptides for therapeutic use against dental caries, dental erosion,
and/or oral candidiasis.
PMID- 28511607
TI - Increasing the use of psychiatric advance directives.
PMID- 28511605
TI - 'It was all intertwined': Illness representations and self-management in patients
with cancer and anxiety/depression.
AB - OBJECTIVE: Cancer and anxiety/depression frequently co-occur, leading to poorer
outcomes for these illnesses. However, the majority of existing research
investigates how participants view single illnesses alone. This study aimed to
explore the content of individuals' multimorbid representations and how these
relate to their coping behaviours and self-management strategies for cancer and
anxiety/depression. DESIGN: A semi-structured qualitative research design with
theoretical thematic analysis. MAIN OUTCOME MEASURES: Multimorbid illness
representations, coping behaviours, and self-management strategies. RESULTS: In
interviews with 21 participants multimorbid representations varied, three
participants viewed cancer and anxiety/depression as unrelated, five participants
were uncertain about the relationship between cancer and anxiety/depression, and
the majority of participants perceived cancer and anxiety/depression as related.
This third group of participants often described relationships as causal, with
representations having both positive and negative influences on coping behaviours
and self-management strategies. Representations were shown to change over the
course of the cancer experience, with fear of cancer recurrence and the influence
of participants' most challenging illness also discussed. CONCLUSIONS: People
hold multimorbid illness representations that can influence self-management. An
awareness of these representations by researchers, health professionals, and
patients is important for the creation of future interventions that aim to
improve and maintain patient wellbeing.
PMID- 28511609
TI - Why the history of nursing ethics matters.
AB - Modern American nursing has an extensive ethical heritage literature that extends
from the 1870s to 1965 when the American Nurses Association issued a policy paper
that called for moving nursing education out of hospital diploma programs and
into colleges and universities. One consequence of this move was the dispersion
of nursing libraries and the loss of nursing ethics textbooks, as they were
largely not brought over into the college libraries. In addition to approximately
100 nursing ethics textbooks, the nursing ethics heritage literature also
includes hundreds of journal articles that are often made less accessible in
modern databases that concentrate on the past 20 or 30 years. A second
consequence of nursing's movement into colleges and universities is that ethics
was no longer taught by nursing faculty, but becomes separated and placed as a
discrete ethics (later bioethics) course in departments of philosophy or
theology. These courses were medically identified and rarely incorporated
authentic nursing content. This shift in nursing education occurs
contemporaneously with the rise of the field of bioethics. Bioethics is rapidly
embraced by nursing, and as it develops within nursing, it fails to incorporate
the rich ethical heritage, history, and literature of nursing prior to the
development of the field of bioethics. This creates a radical disjunction in
nursing's ethics; a failure to more adequately explore the moral identity of
nursing; the development of an ethics with a lack of fit with nursing's ethical
history, literature, and theory; a neglect of nursing's ideal of service; a
diminution of the scope and richness of nursing ethics as social ethics; and a
loss of nursing ethical heritage of social justice activism and education. We
must reclaim nursing's rich and capacious ethics heritage literature; the history
of nursing ethics matters profoundly.
PMID- 28511610
TI - Women without vulvodynia can have a positive 'Q-tip test': a cross sectional
study.
AB - BACKGROUND: Vulvodynia is a frequently missed pathology, often confused with
vaginismus. The Q-tip test (QTT) is fundamental for the diagnosis; however, there
is lack of data about its performance in asymptomatic women. OBJECTIVE: This
study intended to evaluate the QTT for painful vestibular spots in asymptomatic
women. METHODS: Q-tips were gently pressed at different areas of the vulvar
vestibule to obtain a 0-10 score representing the pain felt. This was performed
in 267 consecutive patients presenting to the gynecology outpatient clinic for
reasons other than vulvovaginal complaints. A questionnaire was done to evaluate
the possibility of unrecognized vulvodynia. RESULTS: Out of the 267 women, 18
(6.7%) fitted the diagnosis of vulvodynia and were excluded from the analysis. Of
the remaining 249, 41 (16.5%) had a positive QTT. We could not find differences
in the sexual activity rate between women with and without a positive QTT. No
demographic differences could be found between the two groups. Only depression
was more common in women with a positive QTT [31.7% (13/41) versus 10.8%
(21/208), p=.001). CONCLUSIONS: Asymptomatic women can have painful vestibular
spots in the absence of vulvodynia. A positive QTT cannot be considered
equivalent to vulvodynia, highlighting the need for extensive workup of these
women before that diagnosis can be assumed.
PMID- 28511611
TI - Arthroscopic Assisted Resection of Triangular Fibrocartilage Complex Lesions: A
19-Year Follow-up.
AB - BACKGROUND: This study assesses long-term functional and subjective outcomes
following arthroscopic assisted resection of lesions of the triangular
fibrocartilage complex (TFCC). METHODS: Functional and subjective outcomes were
assessed based on review of patient charts for patient demographic
characteristics, comprehensive clinical evaluation, obtained radiographs, and
patient-reported questionnaires. RESULTS: Fifteen patients, of whom 9 were
female, and 10 dominant wrists, were included in this study. Median age was 60
(range, 37-73) years, and median duration of follow-up was 19 (range, 18-21)
years. Median Mayo Wrist Score was 85 (range, 45-100). Four patients scored
excellent, 7 good, 3 fair, and 1 poor result according to the Modified Mayo Wrist
Score. Median Quick Disabilities of the Arm, Shoulder and Arm was 20 (range, 0
45) and Patient-Rated Wrist and Hand Evaluation was 8 (range, 0-61). Patients
reported high rate for satisfaction and low rate for pain. All patients presented
intact stability of the distal radioulnar joint. CONCLUSIONS: This study
demonstrates persisting satisfactory subjective and functional outcomes for
patients following arthroscopic assisted resection for lesions of the TFCC at 19
years of follow-up. Arthroscopically assisted resection of selected TFCC lesions
seems to be both a safe and efficient procedure.
PMID- 28511612
TI - NGS analysis on tumor tissue and cfDNA for genotype-directed therapy in
metastatic NSCLC patients. Between hope and hype?
AB - INTRODUCTION: The advent of genomic based precision medicine led to the
implementation of biomarker testing in metastatic non-small cell lung cancer
(NSCLC) patients. Next generation sequencing (NGS) has been recently implemented
to routine diagnostic requirements in lung oncology. Areas covered: Two cases of
patients with metastatic NSCLC for whom NGS analysis performed on both tumor and
liquid biopsy has not improved the clinical course of their disease are reported.
These cases illustrate the difficulty of the so-called 'personalized or
precision' medicine in clinical routine practice for metastatic NSCLC. Expert
commentary: Discovery and detection of critical cancer-gene alterations better
indicates targeted therapies that must be administered to improve the care of
NSCLC patients in the personalized medicine era. There has been much interest in
the literature and the scientific community for NGS tailored therapies approach
for patients. However, there may be a gap between this theoretical stratified
medicine and clinical practice. The advantages and drawbacks of NGS on tumor
tissue and cell-free DNA for metastatic NSCLC are discussed.
PMID- 28511613
TI - Antimicrobial activity and molecular docking studies of a novel anthraquinone
from a marine-derived fungus Aspergillus versicolor.
AB - A novel anthraquinone, 2-(dimethoxymethyl)-1-hydroxyanthracene-9,10-dione (1),
together with nine known compounds (2-10), were isolated from the fermentation of
Aspergillus versicolor derived from deep sea sediment. Their structures were
established through spectroscopic methods. Compound 1 exhibited strong inhibitory
activities against MRSA ATCC 43300 and MRSA CGMCC 1.12409 (with MIC values of 3.9
and 7.8 MUg/mL respectively) and moderate activities against tested strains of
Vibrio (with MIC values ranging from 15.6 to 62.5 MUg/mL). Compound 1 was
subjected to molecular docking studies for inhibition of topoisomerase IV and
AmpC beta-lactamase enzymes indicating its usefulness as antimicrobial agent.
PMID- 28511616
TI - Bayesian meta-analysis: The role of the between-sample heterogeneity.
AB - The random effect approach for meta-analysis was motivated by a lack of
consistent assessment of homogeneity of treatment effect before pooling. The
random effect model assumes that the distribution of the treatment effect is
fully heterogenous across the experiments. However, other models arising by
grouping some of the experiments are plausible. We illustrate on simulated binary
experiments that the fully heterogenous model gives a poor meta-inference when
fully heterogeneity is not the true model and that the knowledge of the true
cluster model considerably improves the inference. We propose the use of a
Bayesian model selection procedure for estimating the true cluster model, and
Bayesian model averaging to incorporate into the meta-analysis the clustering
estimation. A well-known meta-analysis for six major multicentre trials to assess
the efficacy of a given dose of aspirin in post-myocardial infarction patients is
reanalysed.
PMID- 28511614
TI - A new topical panthenol-containing emollient for maintenance treatment of
childhood atopic dermatitis: results from a multicenter prospective study.
AB - PURPOSE: A study was conducted with a new topical panthenol-containing emollient
(NTP-CE) to investigate the efficacy and safety of a 3-month maintenance
treatment in infants and children with stabilized mild atopic dermatitis (AD).
METHODS: After the stabilization phase (up to 2 months) using a corticosteroid
free topical medical device, 108 subjects (aged 2-49 months) with a SCORing AD
(SCORAD) on the target area of <5, were randomized to receive NTP-CE (N = 52) or
reference emollient (N = 56) twice-daily for ~3 months. SCORAD scores, occurrence
of flares, and tolerability were assessed at regular intervals. RESULTS: In both
groups, local SCORAD decreased during the study with a mean change from baseline
(=end of stabilization phase) of -1.2 +/- 1.3 (NTP-CE) and -1.0 +/- 1.9. Kaplan
Meier analysis provided success rates (i.e. proportion of subjects without flares
at study end) of 96 and 77% for the NTP-CE and reference group, respectively (p
=.083, log-rank test). Mean time to flare-up was 47 days (range: 29-65) in the
NTP CE group and 50 days (6-100). Study products were well tolerated.
CONCLUSIONS: Our results indicate that NTP-CE is efficacious and safe when used
for maintenance treatment of mild childhood AD.
PMID- 28511617
TI - Secondary Procedures Following Iliac Branch Device Treatment of Aneurysms
Involving the Iliac Bifurcation: The pELVIS Registry.
AB - PURPOSE: To evaluate the incidence and reasons for secondary procedures in
patients treated with iliac branch devices (IBDs) for isolated iliac aneurysm or
aortoiliac aneurysms involving the iliac bifurcation. METHODS: Between January
2005 and December 2015, 575 surgical-high-risk patients (mean age 72.0+/-8.4
years; 558 men) with isolated iliac aneurysms (n=79) or aortoiliac aneurysms
involving the iliac bifurcation (n=496) were treated with placement of 650 ZBIS
or Gore IBDs (75 bilateral) in 6 European centers. The primary outcome was
procedure-related reinterventions for occlusion or high-grade (>70%) stenosis of
the bridging device, occlusion of the ipsilateral common or external iliac artery
(EIA), type I/III endoleak, rupture, or infection following IBD implantation.
Clinical and radiological data were analyzed based on preset definitions of
comorbidities, aneurysm morphology, intraoperative variables, and follow-up
strategies. RESULTS: Nine (1.6%) reinterventions were performed within 30 days
for occlusion or endoleak. Among 10 (1.5%) occluded EIAs ipsilateral to a
deployed IBD, 6 underwent a reintervention with additional stent placement after
thrombolysis (n=4) or a femorofemoral or iliofemoral crossover bypass (n=2).
Three of 14 patients with early type I endoleak had a reintervention for an
insufficient proximal sealing zone (stent-grafts in 2 common iliac arteries and 1
bifurcated endograft). Mean clinical and radiological follow-up were 32.6+/-9.9
and 29.8+/-21.1 months, respectively. Forty-two (7.3%) patients underwent
reinterventions in the follow-up period. The overall postoperative reintervention
rate was 8.9%. Both external and common iliac segments occluded in 30 (4.6%)
IBDs; 2 patients had a crossover bypass and 14 were treated with endovascular
techniques. In the other 14 patients, no specific treatment was performed. Seven
(1.2%) patients with isolated EIA occlusion were treated during follow-up.
Nineteen of the overall 28 patients with type I endoleak underwent endovascular
repair. The other 9 were under radiological surveillance due to less significant
(<5 mm) sac increase. No reintervention was performed to recanalize 11 (1.6%)
occluded internal iliac arteries. CONCLUSION: Midterm experience with placement
of IBDs is associated with a low incidence of secondary procedures due to type I
endoleaks and occlusions. The main reasons for reinterventions seem to be short
proximal sealing zone and poor conformability of the ZBIS device in elongated
EIAs.
PMID- 28511619
TI - Daylight photodynamic therapy in Scotland.
AB - Chronic sun-induced dysplastic skin changes (actinic keratoses) are extremely
common in fair-skinned people in Scotland. These changes are a major cause of
morbidity and may develop into skin cancer. Actinic keratoses are often extensive
and pose a therapeutic challenge as field-directed treatment is required for
chronic disease management. One such treatment approach is hospital-based
photodynamic therapy, which is a well-established treatment in Scotland for
actinic keratoses, using a photosensitiser pro-drug and red LED light
irradiation. However, photodynamic therapy using daylight as the activating light
source is increasingly and effectively used in continental Europe, but had not
been explored in Scotland until we initiated this in 2013. We report our
experience of daylight photodynamic therapy in 64 patient-treatment courses and
demonstrate that this can be an effective, well-tolerated treatment, which is
liked by patients. Our most recent data show that most patients (73%) achieved
clearance or at least a good response to treatment and had high levels of
satisfaction with daylight photodynamic therapy. Daylight exposure measurements
indicated that treatment is feasible in Scotland between April to September.
Daylight photodynamic therapy is an important advancement in treatment options
for Scottish patients with extensive pre-cancerous field changes and provides
opportunities for home-based treatment and increased efficiency of photodynamic
therapy services.
PMID- 28511618
TI - Midterm Results of Low-Profile Stents to Treat Atherosclerotic Iliac Artery
Disease.
AB - PURPOSE: To evaluate the safety and effectiveness of low-profile 4-F stents for
the treatment of atherosclerotic iliac artery lesions. METHODS: Between January
2009 and December 2015, 63 patients (mean age 69.3 years; 42 men) received low
profile stents (Astron Pulsar or Pulsar-18) at the discretion of the operator to
treat iliac artery occlusive disease. The majority of patients (40, 63.5%) had
critical limb ischemia; 36 of 82 lesions were total occlusions. All procedures
were performed with 4-F equipment. Outcomes evaluated included mortality, patency
(primary, assisted primary, and secondary), absence of target lesion
revascularization (TLR), and limb salvage. Associations of patient and procedure
variables with patency and TLR outcomes were sought with univariate and
multivariate analysis. RESULTS: Via a brachial (n=46/63) or femoral (n=17/63)
access, 82 stents were successfully deployed to treat the 82 lesions, with <30%
residual stenosis. The overall access-related complication rate was 1.6%
(brachial artery occlusion). Mean duration of follow-up was 24.1+/-22.3 months
(range 1-72), during which 3 patients died and 1 major amputation occurred at 10
months. The 4-year Kaplan-Meier estimate of primary patency was 76.9% (95% CI
70.2% to 83.6%); the assisted primary and secondary patency estimates were 79.3%
(95% CI 73% to 85.6%) and 91% (95% CI 84.5% to 97.5%). The 4-year freedom from
TLR estimate was 73.8% (95% CI 67.4% to 80.2%). On multivariate analysis, the
only associations confirmed involved Rutherford category 5/6 with primary patency
(hazard ratio [HR] 5.7, 95% CI 4.4 to 7, p=0.02) and assisted primary patency (HR
6.1, 95% CI 4.9 to 7.3, p=0.01). CONCLUSION: Use of a low-profile 4-F stent in
atherosclerotic iliac lesions was safe and effective. At 4 years, the overall
patency and the absence of TLR were good. Midterm outcomes were poor in patients
with Rutherford category 5/6 ischemia. Finally, the use of stents with a >=6-mm
diameter and postdeployment balloon dilation are recommended in all cases.
PMID- 28511620
TI - Is children's listening effort in background noise influenced by the speaker's
voice quality?
AB - The present study aims at exploring the influence of voice quality on listening
effort in children performing a language comprehension test with sentences of
increasing difficulty. Listening effort is explored in relation to gender ( =
cisgender). The study has a between-groups design. Ninety-three mainstreamed
children aged 8;2 to 9;3 with typical language development participated. The
children were randomly assigned to two groups (n = 46/47) with equal allocation
of boys and girls and for the analysis to four groups depending of gender and
voice condition. Working memory capacity and executive functions were tested in
quiet. A digital version of a language comprehension test (the TROG-2) was used
to measure the effect of voice quality on listening effort, measured as response
time in a forced-choice paradigm. The groups listened to sentences through
recordings of the same female voice, one group with a typical voice and one with
a dysphonic voice, both in competing multi-talker babble noise. Response times
were logged after a time buffer between the sentence-ending and indication of
response. There was a significant increase in response times with increased task
difficulty and response times between the two voice conditions differed
significantly. The girls in the dysphonic condition were slower with increasing
task difficulty. A dysphonic voice clearly adds to the noise burden and listening
effort is greater in girls than in boys when the teacher speaks with dysphonic
voice in a noisy background. These findings might mirror gender differences as
for coping strategies in challenging contexts and have important implications for
education.
PMID- 28511621
TI - The effect of exercise training on characteristics of exercise oscillatory
ventilation in chronic heart failure - Reply to the Letter to the Editor.
PMID- 28511622
TI - The effect of exercise training on exercise oscillatory ventilation in heart
failure.
PMID- 28511624
TI - Ten Years After.
PMID- 28511625
TI - Effects of Smoking on Clinical Foot and Ankle Practice.
PMID- 28511627
TI - Short interpregnancy intervals and associated risk of preterm birth in Asians and
Pacific Islanders.
AB - PURPOSE: The prevalence of short interpregnancy intervals (IPIs) and associated
rates of preterm birth has been understudied in Asian and Pacific Islander
populations. We sought to estimate rates of short IPI among Asian subgroups and
Pacific Islanders and associated risk of preterm birth. MATERIALS AND METHODS:
For this retrospective cohort study, we linked records of women in California
with a first birth in 1999-2000 and a second birth before 2005 with hospital
discharge data. We used multivariate modeling to determine whether specific Asian
ethnicities and Pacific Islanders were at greater risk of short IPI (<6 months, 6
18 months) and if a short IPI increased risk for preterm birth in these groups.
RESULTS: Our sample included 189,931 women. In multivariable analyses, Asian
subgroups and Pacific Islanders were more likely to have an IPI <6 months than
were White women (Pacific Islanders: OR 3.31 (95%CI [2.7, 4.1]); Filipinas: OR
1.51 (95%CI [1.33, 1.71]); Southeast Asians: OR 1.93 (95%CI [1.73, 2.1]); East
Asians: OR 1.65 (95%CI [1.48, 1.84]); other Asians: OR 2.04 (95%CI [1.70, 2.4])).
CONCLUSIONS: Asian and Pacific Islander women have higher rates of IPI <6 months,
but this did not significantly increase their risk of preterm birth.
PMID- 28511629
TI - Letter to the Editor Re: Zeidman LA, Stone J, Kondziella D. New revelations about
Hans Berger, father of the electroencephalogram (EEG), and his ties to the Third
Reich. J Child Neurol. 2014;29:1002-1010.
PMID- 28511631
TI - Reversible Cerebral Vasoconstriction Syndrome in Pediatrics: A Case Series and
Review.
AB - Reversible cerebral vasoconstriction syndrome is a transient vasculopathy
associated with severe headaches and stroke. In most cases of reversible cerebral
vasoconstriction syndrome, there is a precipitating event or trigger, such as
pregnancy, serotonin agonist treatment or illicit drug use. The authors present 2
pediatric cases of reversible cerebral vasoconstriction syndrome and review the
previous 11 pediatric cases in the literature. In many instances, the clinical
and radiographic features are similar in both pediatric and adult cases. In the
pediatric group, reported potential triggers include trauma (1/13), exercise
(2/13), water to the face (3/13), hypertension (3/13), and medication or
substance use (4/13). One surprising difference is that 11 out of 13 pediatric
patients with reversible cerebral vasoconstriction syndrome are male while most
cases in adults are female. Many of the pediatric patients with reversible
cerebral vasoconstriction syndrome were treated with a calcium channel blocker
and the overall outcome of pediatric reversible cerebral vasoconstriction
syndrome was good, with most patients experiencing a full recovery.
PMID- 28511630
TI - Corpus Callosotomy for Intractable Epilepsy Revisited: The Children's Hospital of
Michigan Series.
AB - Corpus callosotomy is a palliative procedure performed to reduce the severity of
drug-resistant epilepsy. The authors assessed its efficacy on different seizure
types in 20 subjects (age range 5-19 years); 8 with active vagus nerve
stimulator. Fifteen had complete callosotomy, 3 had anterior 2/3, and 2 had
anterior 2/3 followed later by complete callosotomy. Ten had endoscopic approach.
In all, 65% had >= 50% reduction of generalized seizures leading to falls
(atonic, tonic, myoclonic); 35% became seizure-free (follow-up period: 6 months
to 9 years; mean 3 years). Seizure outcome distribution was better for
generalized than for partial seizures ( P = .003). Endoscopic approach was as
effective as transcranial approach. Seven subjects who failed vagus nerve
stimulator therapy responded with >=50% seizure reduction. Corpus callosotomy is
an effective treatment for intractable generalized epilepsy leading to falls with
significant seizure reduction or even elimination of seizures, in the majority of
children.
PMID- 28511632
TI - Mislabeling of Study Design and Overstatement of Findings in "Rechallenging
Statin Therapy in Veterans With Statin-Induced Myopathy Post Vitamin D
Replenishment".
PMID- 28511633
TI - Authors' Response.
PMID- 28511634
TI - Human factors considerations in designing for infection prevention and control in
neonatal care - findings from a pre-design inquiry.
AB - Qualitative data collection methods drawn from the early stages of human-centred
design frameworks combined with thematic analysis were used to develop an
understanding of infection prevention practice within an existing neonatal
intensive care unit. Findings were used to generate a framework of understanding
which in turn helped inform a baseline approach for future research and design
development. The study revealed that a lack of clarity between infection
transmission zones and a lack of design attributes needed to uphold infection
prevention measures may be undermining healthcare workers' understanding and
application of good practice. The issue may be further complicated by well
intentioned behavioural attitudes to meeting work objectives; undue influences
from spatial constraints; the influence of inadvertent and excessive touch-based
interactions; physical and/or cognitive exertion to maintain transmission
barriers; and the impact of expanding job design and increased workload to
supplement for lack of effective barriers. Practitioner Summary: Despite high
hand hygiene compliance within a neonatal intensive care unit, healthcare workers
expressed concerns about the unit design and infection prevention practice. Early
inquiry methods from human-centred design and thematic analysis helped develop a
framework to understand how design can be used to aid infection prevention.
PMID- 28511635
TI - Review of Techniques to Achieve Optical Surface Cleanliness and Their Potential
Application to Surgical Endoscopes.
AB - A clear visualization of the operative field is of critical importance in
endoscopic surgery. During surgery the endoscope lens can get fouled by body
fluids (eg, blood), ground substance, rinsing fluid, bone dust, or smoke plumes,
resulting in visual impairment. As a result, surgeons spend part of the procedure
on intermittent cleaning of the endoscope lens. Current cleaning methods that
rely on manual wiping or a lens irrigation system are still far from ideal,
leading to longer procedure times, dirtying of the surgical site, and reduced
visual acuity, potentially reducing patient safety. With the goal of finding a
solution to these issues, a literature review was conducted to identify and
categorize existing techniques capable of achieving optically clean surfaces, and
to show which techniques can potentially be implemented in surgical practice. The
review found that the most promising method for achieving surface cleanliness
consists of a hybrid solution, namely, that of a hydrophilic or hydrophobic
coating on the endoscope lens and the use of the existing lens irrigation system.
PMID- 28511636
TI - HPV prevalence and type distribution in Cypriot women with cervical cytological
abnormalities.
AB - BACKGROUND: Human papillomavirus (HPV) is the most common sexually transmitted
agent, and it can cause cervical lesions and cancer in females. Currently,
information regarding the prevalence of HPV in Cyprus is lacking. The aim of this
study was to evaluate the HPV type-specific prevalence in 596 women, aged 19-65
years, with cytological abnormalities. Additionally, in a subset of 348 women for
whom cytology results of the Pap test were available, the association between HPV
infection and cervical disease was investigated. METHODS: HPV detection and
typing was carried out using PCR and restriction fragment length polymorphism
analysis, respectively. RESULTS: Overall, the HPV prevalence was 72.8%, and it
was shown to be age dependent, with a decreasing prevalence until the age of 45
years (p = 0.0018, chi2). Two hundred and fifty-eight women (59.4%) were infected
with high-risk HPV, 151 (34.8%) with low-risk HPV, and 25 (5.8%) with HPV types
of unknown risk. The most common high-risk HPV type was HPV16 (17.7%), followed
by HPV31 (12.9%), HPV58 (7.1%), HPV68 (4.6%), HPV18 (4.1%), and HPV56 (3.7%).
Among the women for whom cytology results were available, 268 (77%) were HPV
positive, with a sample distribution as follows: 188 (74%) had atypical squamous
cells of undetermined significance (ASCUS), 61 (85.9%) had low-grade squamous
intraepithelial lesion (L-SIL), and 19 (82.6%) had high-grade squamous
intraepithelial lesion (H-SIL). HPV16 was the most common type among women
affected by L-SIL (19.7%) and H-SIL (15.8%), with HPV31 being the most common
type in women affected by ASCUS (16.5%). CONCLUSIONS: The present study provides
the first epidemiological data related to HPV prevalence and type distribution in
Cypriot women with cytological abnormalities.
PMID- 28511637
TI - The cytokine polymorphisms affecting Th1/Th2 increase the susceptibility to, and
severity of, chronic ITP.
AB - BACKGROUND: T-helper cell type 1 (Th1) polarization in chronic immune
thrombocytopenia (cITP) has been reported at the protein and mRNA levels. We
evaluated the impact of Th1/Th2 cytokine and cytokine receptor functional
polymorphisms on both susceptibility to, and severity of, cITP. We analysed IFN
gamma + 874 T/A, IFN-gammaR -611G/A, IL-4 -590C/T, and IL-4Ralpha Q576R
polymorphisms in 126 cITP patients (male/female: 34/92; median age: 47.7 years)
and 202 healthy control donors. Genotyping was determined by PCR and direct
sequencing. The Th1/Th2 ratio was detected in peripheral blood mononuclear cells
via flow cytometry. RESULTS: cITP patients had a higher frequency of the IL
4Ralpha 576 non-QQ genotype compared to healthy subjects (P = 0.04). cITP
patients with the IFN-gamma +874 non-AA genotype (high expression type) showed
more severe thrombocytopenia than those with the AA genotype (P < 0.05). cITP
patients had a significantly higher Th1/Th2 ratio than control patients (P <
0.01); this ratio was inversely correlated with platelet counts. Furthermore,
patients with both IFN-gamma +874 non-AA genotype (high expression type) and IFN
gammaR -611 non-AA genotype (high-function type) had a significantly higher
Th1/Th2 ratio (P < 0.05). CONCLUSIONS: The cytokine polymorphisms affecting
Th1/Th2 increase the susceptibility to, and severity of, chronic ITP.
PMID- 28511638
TI - Screening for tuberculosis in an urban shelter for homeless in Switzerland: a
prospective study.
AB - BACKGROUND: Whereas high risk groups such as asylum seekers are systematically
screened for active tuberculosis (TB) upon entry in Switzerland, this strategy
does not apply to homeless persons despite a reported high risk. Geneva health
and social authorities implemented an intersectoral project to screen for active
TB in homeless persons. We aimed to assess acceptability of this program and
prevalence of active TB in this group. METHODS: This prospective study targeted
all homeless adults registering for shelter accommodation in Geneva during winter
2015. Applicants were proposed a questionnaire-based screening ( www.tb-screen.ch
) exploring epidemiological and clinical risk factors for active TB. Participants
with a positive score underwent diagnostic procedures at Geneva University
Hospital. Enhanced TB surveillance targeting homeless persons in the community
was continued 3 months after the study termination. RESULTS: Overall, 726/832
(87.3%) homeless persons accepted the screening procedure. Most were young male
migrants without access to care in Switzerland. Male gender (adjusted OR: 2.14;
95% confidence interval: 1.27-3.62), age below 25 years (aOR: 4.16; 95% CI: 1.27
13.64) and short duration of homelessness (aOR: 1.75; 95% CI: 1.06-2.87) were
predictors of acceptance. Thirty (4.1%) had positive screening scores but none of
the 24 who underwent further testing had active TB. Post-study surveillance did
not identify any incident case in Geneva. CONCLUSIONS: Active TB screening
targeting highly mobile homeless persons in shelters was well accepted and
feasible. The participants' sociodemographic profile highlighted the
heterogeneity of homeless groups in Europe and the null TB prevalence the
variability of their active TB risks. These findings underline the feasibility of
health programs targeting this hard to reach group and the need for close
monitoring of this social group considering the rapid changes in international
mobility patterns to tailor preventive and screening strategies to the local
context.
PMID- 28511639
TI - Physical activity among hospitalized older adults - an observational study.
AB - BACKGROUND: Low level of physical activity is common among hospitalized older
adults and is associated with worse prognosis. The aim of this paper is to
describe the pattern and level of physical activity in a group of hospitalized
older adults and to identify factors associated with physical activity. METHODS:
We measured physical activity on day three after admission using accelerometer
based activity monitors and time in upright position as outcome measure. We
collected data of physical function (Short Physical Performance Battery, SPPB. 0
12), cognitive function (Mini Mental Status Examination, MMSE, 0-30 and diagnosis
of cognitive impairment at discharge, yes/no), personal Activities of Daily
Living (p-ADL, Barthel Index, BI, 0-20) and burden of disease (Cumulative Illness
Rating Scale, CIRS, 0-56). We analyzed data using univariable and multivariable
linear regression models, with time in upright position as dependent variable.
RESULTS: We recorded physical activity in a consecutive sample of thirty-eight
geriatric patients. Their (mean age 82.9 years, SD 6.3) mean time in upright
position one day early after admission was 117.1 min (SD 90.1, n = 38). Mean SPPB
score was 4.3 (SD 3.3, n = 34). Mean MMSE score was 19.3 (SD 5.3, n = 30), 73%
had a diagnosis of cognitive impairment (n = 38). Mean BI score was 16.4 (SD 4.4,
n = 36). Mean CIRS score was 17.0 (SD 4.2, n = 38). There was a significant
association between SPPB score and time in upright position (p = 0.048): For each
one unit increase in SPPB, the expected increase in upright time was 11.7 min.
There was no significant association between age (p = 0.608), diagnosis of
cognitive impairment (p = 0.794), p-ADL status (p = 0.127), CIRS score (p =
0.218) and time in upright position. The overall model fit was R2 0.431.
CONCLUSION: Participants' mean time in upright position one day early after
admission was almost two hours, indicating a high level of physical activity
compared to results from similar studies. Physical function was the only variable
significantly associated with physical activity indicating that SPPB could be a
useful screening tool and that mobilization regimes should be delivered routinely
for patients with reduced physical function.
PMID- 28511640
TI - Tryptophan catabolism and immune activation in primary and chronic HIV infection.
AB - BACKGROUND: Kynurenine/Tryptophan ratio (KTR) is increased in HIV infection, and
linked to immune activation. We hypothesized that early cART initiation results
in lower KTR compared to late initiation. Furthermore, we hypothesized that KTR
prior to cART is a predictor of the magnitude of subsequent reduction in immune
activation. METHODS: Prospective study including 57 HIV-infected individuals
(primary HIV infection (N = 14), early presenters (>350 CD4+ T cells/MUL, N =
24), late presenters (<200 CD4+ T cells/MUL, N = 19)). Kynurenine and tryptophan
were analysed by liquid chromatography-tandem mass spectrometry. Total CD4+ and
CD8+ T cells were determined and proportion of activated CD38 + HLA-DR+ Tcells
was measured using flow cytometry at baseline and after 6 and 12 months of cART.
RESULTS: At baseline, primary HIV infection had higher KTR than early presenters.
However, similar KTR in primary HIV infection and early presenters was found
after cART initiation, while late presenters had higher KTR at all time points.
In primary HIV infection and early presenters, KTR was positively associated with
proportion of activated cells at baseline. Furthermore, in early presenters the
KTR at baseline was associated with proportion of activated cells after 6 and 12
months. Interestingly, in primary HIV infection the KTR at baseline was
positively associated with reduction in proportion of CD8 + CD38 + HLA-DR T cells
after 6 and 12 months. CONCLUSIONS: Lower kynurenine/tryptophan ratio during
follow-up was found after early initiation of cART. KTR in primary HIV infection
and early presenters was positively associated with immune activation.
Importantly, KTR in primary HIV infection predicted the magnitude of subsequent
reduction in immune activation. Thus, a beneficial effect of early cART on KTR
was suggested.
PMID- 28511641
TI - Network-based regularization for high dimensional SNP data in the case-control
study of Type 2 diabetes.
AB - BACKGROUND: Over the past decades, the prevalence of type 2 diabetes mellitus
(T2D) has been steadily increasing around the world. Despite large efforts
devoted to better understand the genetic basis of the disease, the identified
susceptibility loci can only account for a small portion of the T2D heritability.
Some of the existing approaches proposed for the high dimensional genetic data
from the T2D case-control study are limited by analyzing a few number of SNPs at
a time from a large pool of SNPs, by ignoring the correlations among SNPs and by
adopting inefficient selection techniques. METHODS: We propose a network
constrained regularization method to select important SNPs by taking the linkage
disequilibrium into account. To accomodate the case control study, an iteratively
reweighted least square algorithm has been developed within the coordinate
descent framework where optimization of the regularized logistic loss function is
performed with respect to one parameter at a time and iteratively cycle through
all the parameters until convergence. RESULTS: In this article, a novel approach
is developed to identify important SNPs more effectively through incorporating
the interconnections among them in the regularized selection. A coordinate
descent based iteratively reweighed least squares (IRLS) algorithm has been
proposed. CONCLUSIONS: Both the simulation study and the analysis of the Nurses's
Health Study, a case-control study of type 2 diabetes data with high dimensional
SNP measurements, demonstrate the advantage of the network based approach over
the competing alternatives.
PMID- 28511642
TI - Impact of a workplace 'sit less, move more' program on efficiency-related
outcomes of office employees.
AB - BACKGROUND: Few studies have examined the impact of 'sit less, move more'
interventions on workplace performance. This study assessed the short and mid
term impacts of and patterns of change within, a 19-week workplace web-based
intervention (Walk@WorkSpain; W@WS; 2010-11) on employees' presenteeism, mental
well-being and lost work performance. METHODS: A site randomised control trial
recruited employees at six Spanish university campuses (n = 264; 42 +/- 10 years;
171 female), assigned by worksite and campus to an Intervention (IG; used W@WS; n
= 129; 87 female) or an active Comparison group (A-CG; pedometer, paper diary and
self-reported sitting time; n = 135; 84 female). A linear mixed model assessed
changes between the baseline, ramping (8 weeks), maintenance (11 weeks) and
follow-up (two months) phases for the IG versus A-CG on (i) % of lost work
productivity (Work Limitations Questionnaire; WLQ); (ii) three scales for
presenteeism (WLQ) assessing difficulty meeting scheduling demands (Time),
performing cognitive and inter-personal tasks (Mental-Interpersonal) and
decrements in meeting the quantity, quality and timeliness of completed work
(Output); and (iii) mental well-being (Warwick-Edinburgh Mental Well-being
Scale). T-tests assessed differences between groups for changes on the main
outcomes. In the IG, a multivariate logistic regression model identified patterns
of response according to baseline socio-demographic variables, physical activity
and sitting time. RESULTS: There was a significant 2 (group) * 2 (program time
points) interaction for the Time (F [3]=8.69, p = 0.005), Mental-Interpersonal (F
[3]=10.01, p = 0.0185), Output scales for presenteeism (F [3]=8.56, p = 0.0357),
and for % of lost work performance (F [3]=10.31, p = 0.0161). Presenteeism and
lost performance rose significantly in both groups across all study time points;
after baseline performance was consistently better in the IG than in the A-CG.
Better performance was linked to employees being more active (Time, p = 0.041)
and younger (Mental-interpersonal, p = 0.057; Output, p = 0.017). Higher total
sitting time during nonworking days (Mental-interpersonal, p = 0.019) and lower
sitting time during workdays (WLQ Index, p = 0.013) also improved performance.
CONCLUSION: Versus an active comparison condition, a 'sit less, move more'
workplace intervention effectively reduced an array of markers of lost workday
productivity. TRIAL REGISTRATION: NCT02960750 ; Date of registration: 07/11/2016.
PMID- 28511643
TI - Long noncoding RNA expression profile in HLE B-3 cells during TGF-beta2-induced
epithelial-mesenchymal transition.
AB - BACKGROUND: Recent evidence has shown that long noncoding RNAs (lncRNAs) are
involved in the process of epithelial-mesenchymal transition (EMT). However,
little research has focused on the expression profile of lncRNAs during EMT in
human lens epithelial cells (LECs) and their functions have not yet been
described. METHODS: Dysregulated lncRNAs and mRNAs in normal human lens
epithelial B-3(HLE B-3) cells and during transforming growth factor beta2(TGF
beta2)-induced EMT were analyzed via lncRNA microarray. Gene Ontology (GO) and
Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analyses of differentially
expressed mRNAs were performed to identify their functions and pathologic
pathways. Six candidate lncRNAs were validated via quantitative real-time reverse
transcription polymerase chain reaction(qRT-PCR) to confirm the microarray data.
RESULTS: A total of 775 lncRNAs (325 up-regulated and 450 down-regulated) and 935
mRNAs (329 up-regulated and 606 down-regulated) were differentially expressed in
HLE B-3 cells during TGF-beta2-induced EMT compared to normal HLE B-3 cells. GO
and KEGG Pathway analyses indicated the functions of differentially expressed
mRNAs in the TGF-beta2-induced EMT in HLE B-3 cells. qRT-PCR confirmed the trends
indicated in microarray analysis for all 6 candidate lncRNAs. CONCLUSION: Our
study lays the foundation for future research in lncRNAs related to EMT in HLE B
3 cells and could provide new avenues for the prevention and treatment of
posterior capsule opacification (PCO).
PMID- 28511644
TI - Relationship between Glycemic Levels and Treatment Outcome among Critically Ill
Children admitted into Emergency Room in Enugu.
AB - BACKGROUND: Critically ill children are those in need of immediate attention on
arrival to an emergency room. The importance of glycemic level measurement as
well as maintaining the patency of the airway, effective breathing and
circulation cannot be overemphasied. It has been highlighted that the peak
hyperglycemia and hypoglycemia predict poor prognosis, longer lengths of hospital
stay and higher mortality. The study aims to assess the relationship between
glycemic level and treatment outcomes as well as length of hospital stay.
METHODS: Analytical cross sectional method was used to study critically ill
children aged >=1 month to <=10 years admitted into the Children Emergency Room
of Enugu State University Teaching Hospital, Enugu. Their admission blood glucose
was done. Interviewer administered questionnaire was used to collect information
including sociodemographics, duration of hospitalization and outcome of
treatment. Data was analysed using SPSS version 20. Chi square, logistic
regressions and Kruskal Wallis tests were done as appropriate. RESULTS: A total
of 300 patients were recruited. One hundred and seventeen (39%) had
hyperglycemia, 62 (20.7%) patients had hypoglycaemia and 121 (40.3%) had
euglycemia. Two hundred and fifty two (84%) were discharged while 48 (16%) died.
There was significant association between glycemic levels and treatment outcome
(p = < 0.001). Among the 48 who died, 12 (25.0%) had euglycemia, 21 (43.75%) had
hypoglycaemia while 15 (31.25%) had hyperglycemia. On multivariate analysis,
there was statistically significant association between hypoglycaemia and
mortality (p = < 0.001). Unadjusted, those children with hypoglycaemia at
presentation were about 4.7 times (UOR = 0.21, 95% Cl: 0.08-0.38) and adjusted,
about 5 times (AOR = 0.20, 95% CI: 0.09-0.47) less likely to survive compared
with those with euglycemia. Although not statistically significant, those with
hyperglycemia were about 1.3 times less likely to survive compared with
euglycemic children, adjusted and unadjusted (UOR = 0.75, 95% Cl: 0.33-1.68).
CONCLUSION: While both hypo- and hyperglycemia are associated with mortality,
hypoglycaemia had a greater effect than hyperglycemia. Glycemic levels
significantly affects treatment outcome.
PMID- 28511645
TI - Therapeutic potential of TAS-115 via c-MET and PDGFRalpha signal inhibition for
synovial sarcoma.
AB - BACKGROUND: The prognosis of synovial sarcoma (SS), an aggressive soft tissue
sarcoma, remains poor. We previously reported that c-MET or platelet-derived
growth factor receptor alpha (PDGFRalpha) signalling pathway is related to SS
progression based upon the findings of phospho-receptor tyrosine kinase (RTK)
arrays. TAS-115 is a novel c-MET/ vascular endothelial growth factor receptor
targeting tyrosine kinase inhibitor that has been shown to inhibit multiple RTKs.
Here we aimed to investigate the therapeutic potential of TAS-115 against SS.
METHODS: We first evaluated which signalling pathway was relevant to the
viability of three human SS cell lines: Yamato-SS, SYO-1 and HS-SY-II. Next, we
assessed the anticancer activity and mechanism of action of TAS-115 in these SS
cell lines. Finally, we compared the ability of TAS-115 to inhibit c-MET and
PDGFRalpha phosphorylation with that of pazopanib. RESULTS: We classified the SS
cell lines as c-MET-dependent or PDGFRalpha-dependent based upon the differences
in the signalling pathway relevant for growth and/or survival. We also found that
c-MET and PDGFRalpha were the primary activators of both phosphatidylinositol 3
kinase/AKT and mitogen-activated protein kinase pathways in c-MET-dependent and
PDGFRalpha-dependent SS cells, respectively. TAS-115 treatment blocked the
phosphorylation of PDGFRalpha as well as that of c-MET and their downstream
effectors, leading to marked growth inhibition in both types of SS cell lines in
in vitro and in vivo studies. Furthermore, PDGFRalpha phosphorylation, on at
least four representative autophosphorylation sites, was impeded by TAS-115
equivalently to pazopanib. CONCLUSIONS: These experimental results have
demonstrated the significance of c-MET and PDGFRalpha signalling for growth
and/or survival of SS tumours. TAS-115 monotherapy may benefit SS patients whose
tumours are dependent upon either c-MET or PDGFRalpha signalling by functioning
as a multiple tyrosine kinase inhibitor to suppress c-MET as well as PDGFRalpha
pathways.
PMID- 28511646
TI - Emergence of microbial diversity due to cross-feeding interactions in a spatial
model of gut microbial metabolism.
AB - BACKGROUND: The human gut contains approximately 1014 bacteria, belonging to
hundreds of different species. Together, these microbial species form a complex
food web that can break down nutrient sources that our own digestive enzymes
cannot handle, including complex polysaccharides, producing short chain fatty
acids and additional metabolites, e.g., vitamin K. Microbial diversity is
important for colonic health: Changes in the composition of the microbiota have
been associated with inflammatory bowel disease, diabetes, obesity and Crohn's
disease, and make the microbiota more vulnerable to infestation by harmful
species, e.g., Clostridium difficile. To get a grip on the controlling factors of
microbial diversity in the gut, we here propose a multi-scale, spatiotemporal
dynamic flux-balance analysis model to study the emergence of metabolic diversity
in a spatial gut-like, tubular environment. The model features genome-scale
metabolic models (GEM) of microbial populations, resource sharing via
extracellular metabolites, and spatial population dynamics and evolution.
RESULTS: In this model, cross-feeding interactions emerge readily, despite the
species' ability to metabolize sugars autonomously. Interestingly, the community
requires cross-feeding for producing a realistic set of short-chain fatty acids
from an input of glucose, If we let the composition of the microbial
subpopulations change during invasion of adjacent space, a complex and stratified
microbiota evolves, with subspecies specializing on cross-feeding interactions
via a mechanism of compensated trait loss. The microbial diversity and
stratification collapse if the flux through the gut is enhanced to mimic
diarrhea. CONCLUSIONS: In conclusion, this in silico model is a helpful tool in
systems biology to predict and explain the controlling factors of microbial
diversity in the gut. It can be extended to include, e.g., complex nutrient
sources, and host-microbiota interactions via the intestinal wall.
PMID- 28511647
TI - Low-smoke chulha in Indian slums: study protocol for a randomised controlled
trial.
AB - BACKGROUND: Biomass fuel is used as a primary cooking source by more than half of
the world's population, contributing to a high burden of disease. Although
cleaner fuels are available, some households continue using solid fuels because
of financial constraints and absence of infrastructure, especially in non
notified slums. The present study documents a randomised controlled study
investigating the efficacy of improved cookstove on the personal exposure to air
pollution and the respiratory health of women and children in an Indian slum. The
improved cookstove was based on co-creation of a low-smoke chulha with local
communities in order to support adaption and sustained uptake. METHODS: The study
will be conducted in a non-notified slum called Ashrayanagar in Bangalore, India.
The study design will be a 1:1 randomised controlled intervention trial,
including 250 households. The intervention group will receive an improved
cookstove (low-smoke chulha) and the control group will continue using either the
traditional cookstove (chulha) or a combination of the traditional stove and the
kerosene/diesel stove. Follow-up time is 1 year. Outcomes include change in lung
function (FEV1/FVC), incidence of pneumonia, change in personal PM2.5 and CO
exposure, incidence of respiratory symptoms (cough, phlegm, wheeze and shortness
of breath), prevalence of other related symptoms (headache and burning eyes),
change in behaviour and adoption of the stove. Ethical clearance was obtained
from the Institutional Ethics Committee of the Indian Institute of Public Health
Hyderabad- Bengaluru Campus. DISCUSSION: The findings from this study aim to
provide insight into the effects of improved cookstoves in urban slums. Results
can give evidence for the decrease of indoor air pollution and the improvement of
respiratory health for children and women. TRIAL REGISTRATION: The trial was
registered with clinicaltrials.gov on 21 June 2016 with the identifier
NCT02821650 ; A Study to Test the Impact of an Improved Chulha on the Respiratory
Health of Women and Children in Indian Slums.
PMID- 28511648
TI - A mathematical model of mechanotransduction reveals how mechanical memory
regulates mesenchymal stem cell fate decisions.
AB - BACKGROUND: Mechanical and biophysical properties of the cellular
microenvironment regulate cell fate decisions. Mesenchymal stem cell (MSC) fate
is influenced by past mechanical dosing (memory), but the mechanisms underlying
this process have not yet been well defined. We have yet to understand how memory
affects specific cell fate decisions, such as the differentiation of MSCs into
neurons, adipocytes, myocytes, and osteoblasts. RESULTS: We study a minimal gene
regulatory network permissive of multi-lineage MSC differentiation into four cell
fates. We present a continuous model that is able to describe the cell fate
transitions that occur during differentiation, and analyze its dynamics with
tools from multistability, bifurcation, and cell fate landscape analysis, and via
stochastic simulation. Whereas experimentally, memory has only been observed
during osteogenic differentiation, this model predicts that memory regions can
exist for each of the four MSC-derived cell lineages. We can predict the
substrate stiffness ranges over which memory drives differentiation; these are
directly testable in an experimental setting. Furthermore, we quantitatively
predict how substrate stiffness and culture duration co-regulate the fate of a
stem cell, and we find that the feedbacks from the differentiating MSC onto its
substrate are critical to preserve mechanical memory. Strikingly, we show that re
seeding MSCs onto a sufficiently soft substrate increases the number of cell
fates accessible. CONCLUSIONS: Control of MSC differentiation is crucial for the
success of much-lauded regenerative therapies based on MSCs. We have predicted
new memory regions that will directly impact this control, and have quantified
the size of the memory region for osteoblasts, as well as the co-regulatory
effects on cell fates of substrate stiffness and culture duration. Taken
together, these results can be used to develop novel strategies to better control
the fates of MSCs in vitro and following transplantation.
PMID- 28511649
TI - IL-10 ameliorates TNF-alpha induced meniscus degeneration in mature meniscal
tissue in vitro.
AB - BACKGROUND: Joint inflammation causes meniscus degeneration and can exacerbate
post-traumatic meniscus injuries by extracellular matrix degradation, cellular de
differentiation and cell death. The aim of this study was to examine whether anti
inflammatory interleukin-10 exerts protective effects in an in vitro model of TNF
alpha-induced meniscus degeneration. METHODS: Meniscus tissue was harvested from
the knees of adult cows. After 24 h of equilibrium explants were simultaneously
treated with bovine TNF-alpha and IL-10. After an incubation time of 72 h cell
death was measured histomorphometrically (nuclear blebbing, NB) and release of
glycosaminoglycans (GAG, DMMB assay) and nitric oxide (NO, Griess-reagent) were
analysed. Transcription levels (mRNA) of matrix degrading enzymes, collagen type
X (COL10A1) and nitric oxide synthetase 2 (NOS2) were measured by quantitative
real time PCR. TNF-alpha-dependent formation of the aggrecanase-specific aggrecan
neoepitope NITEGE was visualised by immunostaining. Differences between groups
were calculated using a one-way ANOVA with a Bonferroni post hoc test. RESULTS:
Administration of IL-10 significantly prevented the TNF-alpha-related cell death
(P .001), release of NO (P .003) and NOS2 expression (P .04). Release of GAG
fragments (P .001), NITEGE formation and expression of MMP3 (P .007), -13 (P .02)
and ADAMTS4 (P .001) were significantly reduced. The TNF-alpha-dependent increase
in COL10A1 expression was also antagonized by IL-10 (P .02). CONCLUSION: IL-10
prevented crucial mechanisms of meniscal degeneration induced by a key cytokine
of OA, TNF-alpha. Administration of IL-10 might improve the biological
regeneration and provide a treatment approach in degenerative meniscus injuries
and in conditions of post-traumatic sports injuries.
PMID- 28511650
TI - Pain, pain intensity and pain disability in high school students are differently
associated with physical activity, screening hours and sleep.
AB - BACKGROUND: Studies exploring the association between physical activity, screen
time and sleep and pain usually focus on a limited number of painful body sites.
Nevertheless, pain at different body sites is likely to be of different nature.
Therefore, this study aims to explore and compare the association between time
spent in self-reported physical activity, in screen based activities and sleeping
and i) pain presence in the last 7-days for 9 different body sites; ii) pain
intensity at 9 different body sites and iii) global disability. METHODS: Nine
hundred sixty nine students completed a questionnaire on pain, time spent in
moderate and vigorous physical activity, screen based time watching TV/DVD,
playing, using mobile phones and computers and sleeping hours. Univariate and
multivariate associations between pain presence, pain intensity and disability
and physical activity, screen based time and sleeping hours were investigated.
RESULTS: Pain presence: sleeping remained in the multivariable model for the
neck, mid back, wrists, knees and ankles/feet (OR 1.17 to 2.11); moderate
physical activity remained in the multivariate model for the neck, shoulders,
wrists, hips and ankles/feet (OR 1.06 to 1.08); vigorous physical activity
remained in the multivariate model for mid back, knees and ankles/feet (OR 1.05
to 1.09) and screen time remained in the multivariate model for the low back (OR
= 2.34. Pain intensity: screen time and moderate physical activity remained in
the multivariable model for pain intensity at the neck, mid back, low back,
shoulder, knees and ankles/feet (Rp2 0.02 to 0.04) and at the wrists (Rp2 =
0.04), respectively. Disability showed no association with sleeping, screen time
or physical activity. CONCLUSIONS: This study suggests both similarities and
differences in the patterns of association between time spent in physical
activity, sleeping and in screen based activities and pain presence at 8
different body sites. In addition, they also suggest that the factors associated
with the presence of pain, pain intensity and pain associated disability are
different.
PMID- 28511651
TI - High-resolution mucociliary transport measurement in live excised large animal
trachea using synchrotron X-ray imaging.
AB - BACKGROUND: The Australian Synchrotron Imaging and Medical Beamline (IMBL) was
designed as the world's widest synchrotron X-ray beam, enabling both clinical
imaging and therapeutic applications for humans as well as the imaging of large
animal models. Our group is developing methods for imaging the airways of newly
developed CF animal models that display human-like lung disease, such as the CF
pig, and we expect that the IMBL can be utilised to image airways in animals of
this size. METHODS: This study utilised samples of excised tracheal tissue to
assess the feasibility, logistics and protocols required for airway imaging in
large animal models such as pigs and sheep at the IMBL. We designed an image
processing algorithm to automatically track and quantify the tracheal mucociliary
transport (MCT) behaviour of 103 MUm diameter high refractive index (HRI) glass
bead marker particles deposited onto the surface of freshly-excised normal sheep
and pig tracheae, and assessed the effects of airway rehydrating aerosols.
RESULTS: We successfully accessed and used scavenged tracheal tissue, identified
the minimum bead size that is visible using our chosen imaging setup, verified
that MCT could be visualised, and that our automated tracking algorithm could
quantify particle motion. The imaging sequences show particles propelled by
cilia, against gravity, up the airway surface, within a well-defined range of
clearance speeds and with examples of 'clumping' behaviour that is consistent
with the in vivo capture and mucus-driven transport of particles. CONCLUSION:
This study demonstrated that the wide beam at the IMBL is suitable for imaging
MCT in ex vivo tissue samples. We are now transitioning to in vivo imaging of MCT
in live pigs, utilising higher X-ray energies and shorter exposures to minimise
motion blur.
PMID- 28511653
TI - Processes and challenges of community mobilisation for latrine promotion under
Nirmal Bharat Abhiyan in rural Odisha, India.
AB - BACKGROUND: Despite efforts to eradicate it, open defecation remains widely
practiced in India, especially in rural areas. Between 2013 and 2014, 50 villages
in one district of Odisha, India, received a sanitation programme under the
Nirmal Bharat Abhiyan (NBA - "Clean India Campaign"), the successor of India's
Total Sanitation Campaign. This paper documents the strategies and processes of
NBA community mobilisation for latrine promotion in these villages and assesses
the strengths and limitations of the mobilisation activities. METHODS: NBA's
community mobilisation activities were observed and assessed against the
programme's theory of change in 10 randomly selected programme villages from
start to finish. Additional data was collected through review of documents,
individual interviews (n = 80) and focus group discussions (n = 26) with staff of
the implementing NGOs and community members. RESULTS: Our study revealed the lack
of a consistent implementation strategy, lack of capacities and facilitation
skills of NGO staff to implement sanitation programmes, political interference,
challenges in accessing government financial incentives for latrine construction,
and lack of clarity on the roles and responsibilities among government and NGO
staff, leading to failure in translating government policies into sustainable
actions. Social divisions and village dynamics related to gender and caste
further constrained the effectiveness of mobilisation activities. Meetings were
often dominated by male members of upper caste households, and excluded low caste
community members and views of women. Community discussions revolved largely
around the government's cash incentive for latrines. Activities aimed at creating
demand for sanitation and use of latrines often resonated poorly with community
members. An assessment by the implementers, 1 year after community mobilisation
found 19% of households had a completed latrine across the 50 villages, a
marginal increase of 7 percentage points over baseline. CONCLUSIONS: In this
setting, the Government of India's NBA programme to increase rural sanitation
coverage and use is hampered by political, programmatic, logistical and socio
structural constraints. Sanitation demand generation was difficult for local
implementing NGOs as village populations had lost trust in organisations due to
previous indications of fraud. Agencies or organisations implementing sanitation
campaigns and conducting sanitation promotions need to enhance their staff's
knowledge and build capacity in order to address important social heterogeneity
within villages. This trial's registration number is NCT01214785 (October 4,
2010).
PMID- 28511652
TI - ING3 promotes prostate cancer growth by activating the androgen receptor.
AB - BACKGROUND: The androgen receptor (AR) is a major driver of prostate cancer, and
increased AR levels and co-activators of the receptor promote the development of
prostate cancer. INhibitor of Growth (ING) proteins target lysine
acetyltransferase or lysine deacetylase complexes to the histone H3K4Me3 mark of
active transcription, to affect chromatin structure and gene expression. ING3 is
a stoichiometric member of the TIP60 lysine acetyltransferase complex implicated
in prostate cancer development. METHODS: Biopsies of 265 patients with prostate
cancer were stained for ING3, pan-cytokeratin, and DNA. LNCaP and C4-2 androgen
responsive cells were used for in vitro assays including immunoprecipitation,
western blotting, Luciferase reporter assay and quantitative polymerase chain
reaction. Cell viability and migration assays were performed in prostate cancer
cell lines using scrambled siRNA or siRNA targeting ING3. RESULTS: We find that
ING3 levels and AR activity positively correlate in prostate cancer. ING3
potentiates androgen effects, increasing expression of androgen-regulated genes
and androgen response element-driven reporters to promote growth and anchorage
independent growth. Conversely, ING3 knockdown inhibits prostate cancer cell
growth and invasion. ING3 activates the AR by serving as a scaffold to increase
interaction between TIP60 and the AR in the cytoplasm, enhancing receptor
acetylation and translocation to the nucleus. Activation is independent of ING3's
ability to target the TIP60 complex to H3K4Me3, identifying a previously unknown
chromatin-independent cytoplasmic activity for ING3. In agreement with in vitro
observations, analysis of The Cancer Genome Atlas (TCGA) data (n = 498) and a
prostate cancer tissue microarray (n = 256) show that ING3 levels are higher in
aggressive prostate cancers, with high levels of ING3 predicting shorter patient
survival in a low AR subgroup. Including ING3 levels with currently used
indicators such as the Gleason score provides more accurate prognosis in primary
prostate cancer. CONCLUSIONS: In contrast to the majority of previous reports
suggesting tumor suppressive functions in other cancers, our observations
identify a clear oncogenic role for ING3, which acts as a co-activator of AR in
prostate cancer. Data from TCGA and our previous and current tissue microarrays
suggest that ING3 levels correlate with AR levels and that in patients with low
levels of the receptor, ING3 level could serve as a useful prognostic biomarker.
PMID- 28511655
TI - Video vs direct laryngoscopy in the ICU: are we asking the right question?
PMID- 28511654
TI - Oxidative profiles of LDL and HDL isolated from women with preeclampsia.
AB - BACKGROUND: Oxidative stress causes biochemical changes in lipids and proteins;
these changes can induce damage to the vascular endothelium and create maternal
complications that are characteristic of preeclampsia. In this study, we
evaluated the oxidative profile of lipoproteins isolated from women with
preeclampsia. METHODS: Thirty women diagnosed with preeclampsia and thirty women
without preeclampsia were included in the study. Lipid-damage biomarkers,
including conjugated dienes, lipohydroperoxides and malondialdehyde, were
measured. The reduction of nitroblue tetrazolium, the formation of dityrosines,
and the carbonylation of proteins were assessed as indicators of protein damage.
The protective activity of HDL-c was evaluated by the paraoxonase-I activity
present on the HDL-c particles. Serum lipid profiles were also quantified in both
groups. Data were analysed using Student's t test and the Pearson correlation
coefficient. RESULTS: Our results demonstrated in PE women evident oxidative
changes in the lipids and proteins in HDL-c and LDL-c particles and the activity
of the antioxidant enzyme PON-I decreased 59.9%. HDL-c exhibited self-defence, as
demonstrated by the negative correlation between paraoxonase-I activity and the
formation of lipohydroperoxides in HDL-c (r = -0.3755, p < 0.005). CONCLUSIONS:
LDL-c and HDL-c isolated from women with preeclampsia show oxidative damage to
lipids and proteins. We propose an oxidative profile based on the oxidation
levels indicated by each of the markers used. We also found that paraoxonase-I is
inactivated in the presence of lipohydroperoxides. Antioxidant support might be
helpful to reduce oxidative stress in patients with preeclampsia. Further
investigations are necessary to define the association between antioxidant
activities and preeclampsia.
PMID- 28511656
TI - A randomized comparison of flow characteristics of semiskeletonized and pedicled
internal thoracic artery preparations in coronary artery bypass.
AB - BACKGROUND: Harvesting the internal thoracic artery (ITA) with
semiskeletonization is an alternative technique between conventional wide pedicle
and skeletonization. It is almost as simple as pedicle harvesting; however, it is
supposed to provide the advantage of graft flow and length. Since the heart is
unique being the only organ which is perfused during diastole, for comparing the
intraoperative graft flow characteristics of semiskeletonization and pedicle
technique, we used diastolic filling (DF) using transit-time flow measurement as
a primary result. The objective of this study is to compare if semiskeletonized
ITA has a greater effect on the intraoperative DF of graft flow versus
conventional pedicled ITA in coronary artery bypass. METHODS: Between July 2015
and May 2016, a prospective evaluation of 60 consecutive patients undergoing
coronary artery bypass grafting for left anterior descending artery
revascularization were randomized to having semiskeletonized (n = 30) or
conventional pedicled (n = 30) ITA graft harvested by the same surgeon.
Intraoperative transit-time flows were obtained. The DF of the ITA graft at the
end of operation was evaluated in two groups. RESULTS: The intraoperative DF was
significantly greater in the semiskeletonized grafts than in the pedicled grafts
(70.50 +/- 14.15 versus 57.6 +/- 19.39%; p = 0.005). No statistical difference
was observed comparing quantitative pulsatile flow and pulsatile index at the end
of the operation in the two groups. However, the free flow of the conduit during
the cardiopulmonary bypass before the anastomosis performed was greater in
semiskeletonized group than in pedicled group (94 +/- 48.37 versus 56.35 +/-
34.90 ml/min; p = 0.003). The total operative time was comparable between two
groups (p = 0.092). CONCLUSIONS: Semiskeletonized ITA resulted in superior DF of
left anterior descending bypass graft flow as compared with pedicled ITA. It is
also provide a greater free flow and length of the graft without the long-delayed
operative time. TRIAL REGISTRATION: Trial registration number (Study ID):
TCTR20160913002 Date of registration: September 10, 2016.
PMID- 28511657
TI - Skilled delivery inequality in Ethiopia: to what extent are the poorest and
uneducated mothers benefiting?
AB - BACKGROUND: The fifth Millennium Development Goal (MDG) targeted at improving
maternal health. In this regard, Ethiopia has shown substantial progresses in the
past two decades. Nonetheless, these impressive gains are unevenly distributed
among Ethiopian women with different socio-economic characteristics. This study
aimed at investigating levels and trends of skilled delivery service, and wealth
and education related inequalities from 2000 to 16. METHODS: Longitudinal data
analysis was conducted on Ethiopian Demographic and Health Survey (EDHS) data of
2000, 2005, 2011 and 2016. The outcome variable was skilled delivery, while data
on economic status and education level were used as dimensions of inequality.
Rate Ratio (RR) and Rate Difference (RD) inequality measures were applied. STATA
for windows version 10.1 statistical software was utilized for data analysis and
presentation. The strength of association of inequality dimensions with the
outcome variable was assessed using a 95% confidence interval. RESULTS: From
total deliveries, 5.62%, 6.3%, 10.8% and 28% of them were attended by skilled
birth attendant in 2000, 2005, 2011 and 2016 respectively. In the most recent
survey (EDHS 2016), proportion of births attended by skilled birth attendance
among women who completed secondary and above education was about 5.42 [95% CI
(4.53, 6.09)] times more when compared to women with no formal education.
Proportion of births attended by skilled birth attendance among women in the
richest quintile was about 5.11 [95% CI (3.98, 6.12)] times higher than that of
women in the poorest quintile. Moreover, gap of inequality on receiving skilled
delivery service has increased substantially from 24.2 (2000) to 53.8 (2016)
percentage points between women in the richest and poorest quintiles; and from
44.9 (2000) to 76.0 (2016) percentage points between women who completed
secondary and above education and women with no formal education. CONCLUSIONS:
Skilled birth attendance remained low and virtually unchanged during the period
2000-2011, but increased substantially in 2016. Gap on wealth and education
related inequalities increased linearly during 2000-16. Most pronounced
inequalities were observed in women's level of education revealing women with no
formal education were the most underserved subgroups. Encouraging women in
education and economic development programs should be strengthened as part of the
effort to attain Universal Health Coverage (UHC) of Sustainable Development Goals
(SDGs) in Ethiopia.
PMID- 28511658
TI - Global Kalman filter approaches to estimate absolute angles of lower limb
segments.
AB - BACKGROUND: In this paper we propose the use of global Kalman filters (KFs) to
estimate absolute angles of lower limb segments. Standard approaches adopt KFs to
improve the performance of inertial sensors based on individual link
configurations. In consequence, for a multi-body system like a lower limb
exoskeleton, the inertial measurements of one link (e.g., the shank) are not
taken into account in other link angle estimations (e.g., foot). Global KF
approaches, on the other hand, correlate the collective contribution of all
signals from lower limb segments observed in the state-space model through the
filtering process. We present a novel global KF (matricial global KF) relying
only on inertial sensor data, and validate both this KF and a previously
presented global KF (Markov Jump Linear Systems, MJLS-based KF), which fuses data
from inertial sensors and encoders from an exoskeleton. We furthermore compare
both methods to the commonly used local KF. RESULTS: The results indicate that
the global KFs performed significantly better than the local KF, with an average
root mean square error (RMSE) of respectively 0.942 degrees for the MJLS-based
KF, 1.167 degrees for the matrical global KF, and 1.202 degrees for the local
KFs. Including the data from the exoskeleton encoders also resulted in a
significant increase in performance. CONCLUSION: The results indicate that the
current practice of using KFs based on local models is suboptimal. Both the
presented KF based on inertial sensor data, as well our previously presented
global approach fusing inertial sensor data with data from exoskeleton encoders,
were superior to local KFs. We therefore recommend to use global KFs for gait
analysis and exoskeleton control.
PMID- 28511659
TI - Antiplasmodial activity of Indigofera spicata root extract against Plasmodium
berghei infection in mice.
AB - BACKGROUND: In addition to pharmacovigilance and pharmaco-economic concerns,
resistance to anti-malarial medicines has been documented in all classes of anti
malarials and this is further worsened by resistance to common insecticides by
malaria vector, which is a major threat to malaria control. As a means of facing
the challenges of searching for new anti-malarial agents, the current study
focused on evaluation of anti-malarial activity of root extract of Indigofera
spicata. METHODS: Chloroquine-sensitive rodent malaria parasite, Plasmodium
berghei (ANKA strain) was used to infect the Swiss Albino mice in 4-day
suppressive and curative models. The crude hydromethanolic root extract of I.
spicata at 200, 400 and 600 mg/kg doses was administered to a group of five mice.
Important parameters, such as level of parasitaemia, packed cell volume (PCV),
survival time, and body weight were determined and the significance of the
differences between mean values of the five groups was analysed by one-way ANOVA
followed by post hoc Tukey's Multiple Comparison test. RESULTS: In both the
suppressive and curative models, 400 and 600 mg/kg doses of the extract
suppressed the level of parasitaemia significantly (p < 0.001) compared to the
vehicle-treated groups, 34.93 and 53.42%, respectively. However, only the mice
which were treated with the 600 mg/kg dose of the extract had significant
difference in their mean survival time. In other parameters, namely PCV and mean
body weight, there was no statistically significant difference between the
extract-treated groups when compared to the negative control. CONCLUSIONS: This
study revealed that the root extract of I. spicata possesses anti-malarial
activity and necessitates further scientific validation.
PMID- 28511660
TI - Simvastatin for patients with acute respiratory distress syndrome: long-term
outcomes and cost-effectiveness from a randomised controlled trial.
AB - BACKGROUND: Simvastatin therapy for patients with acute respiratory distress
syndrome (ARDS) has been shown to be safe and associated with minimal adverse
effects, but it does not improve clinical outcomes. The aim of this research was
to report on mortality and cost-effectiveness of simvastatin in patients with
ARDS at 12 months. METHODS: This was a cost-utility analysis alongside a
multicentre, double-blind, randomised controlled trial carried out in the UK and
Ireland. Five hundred and forty intubated and mechanically ventilated patients
with ARDS were randomly assigned (1:1) to receive once-daily simvastatin (at a
dose of 80 mg) or identical placebo tablets enterally for up to 28 days. RESULTS:
Mortality was lower in the simvastatin group (31.8%, 95% confidence interval (CI)
26.1-37.5) compared to the placebo group (37.3%, 95% CI 31.6-43.0) at 12 months,
although this was not significant. Simvastatin was associated with statistically
significant quality-adjusted life year (QALY) gain (incremental QALYs 0.064, 95%
CI 0.002-0.127) compared to placebo. Simvastatin was also less costly
(incremental total costs -L3601, 95% CI -8061 to 859). At a willingness-to-pay
threshold of L20,000 per QALY, the probability of simvastatin being cost
effective was 99%. Sensitivity analyses indicated that the results were robust to
changes in methodological assumptions with the probability of cost-effectiveness
never dropping below 90%. CONCLUSION: Simvastatin was found to be cost-effective
for the treatment of ARDS, being associated with both a significant QALY gain and
a cost saving. There was no significant reduction in mortality at 12 months,
TRIAL REGISTRATION: ISRCTN, 88244364. Registered 26 November 2010.
PMID- 28511661
TI - A preliminary investigation on the utility of temporal features of Force
Myography in the two-class problem of grasp vs. no-grasp in the presence of upper
extremity movements.
AB - BACKGROUND: In upper-extremity stroke rehabilitation applications, the potential
use of Force Myography (FMG) for detecting grasping is especially relevant, as
the presence of grasping may be indicative of functional activity, which is a key
goal of rehabilitation. To date, most FMG research has focused on the
classification of the raw FMG signal (i.e. instantaneous FMG samples) in order to
determine the state of the hand. However, given the temporal nature of force
generation during grasping, the use of temporal feature extraction techniques may
yield increased accuracy. In this study, the effectiveness of classifying
temporal features of the FMG signal for the two-class grasp detection problem of
"grasp" versus "no grasp" (i.e. no object in hand) was evaluated with ten healthy
participants. The experimental protocol comprised grasp and move tasks, requiring
the use of six different grasp types frequently used in daily living, in
conjunction with arm and hand movements. Data corresponding to arm and hand
movements without grasping were also included to evaluate robustness to false
positives. The temporal features evaluated were mean absolute value (MAV), root
mean squared (RMS), linear fit (LF), parabolic fit (PF), and autoregressive model
(AR). Off-line classification performance of the five temporal features, with a
0.5 s extraction window, were determined and compared to that of the raw FMG
signal using area under the receiver operating curve (AUC). RESULTS: The raw FMG
signal yielded AUC of 0.819 +/- 0.098. LF and PF resulted in the greatest
increases in classification performance, and provided statistically significant
increases in performance. The largest increase obtained was with PF, yielding AUC
of 0.869 +/- 0.061, corresponding to a 6.1% relative increase over the raw FMG
signal. Despite the additional fitting term provided by PF, classification
performance did not significantly improve with PF when compared to LF.
CONCLUSIONS: The results obtained indicate that temporal feature extraction
techniques that derive models of the data within the window may yield modest
improvements in FMG based grasp detection performance. In future studies, the use
of model-based temporal features should be evaluated with FMG data from
individuals with stroke, who might ultimately benefit from this technology.
PMID- 28511662
TI - Response to the Letter to the Editor by Eberhard et al.
AB - In a Letter to the Editor, Eberhard et al. question the validity of our model of
skin snip sensitivity and argue against the use of skin snips to evaluate
onchocerciasis elimination by mass drug administration. Here we discuss their
arguments and compare model predictions with observed data to assess the validity
of our model.
PMID- 28511665
TI - Clone temporal centrality measures for incomplete sequences of graph snapshots.
AB - BACKGROUND: Different phenomena like the spread of a disease, social interactions
or the biological relation between genes can be thought of as dynamic networks.
These can be represented as a sequence of static graphs (so called graph
snapshots). Based on this graph sequences, classical vertex centrality measures
like closeness and betweenness centrality have been extended to quantify the
importance of single vertices within a dynamic network. An implicit assumption
for the calculation of temporal centrality measures is that the graph sequence
contains all information about the network dynamics over time. This assumption is
unlikely to be justified in many real world applications due to limited access to
fully observed network data. Incompletely observed graph sequences lack important
information about duration or existence of edges and may result in biased
temporal centrality values. RESULTS: To account for this incompleteness, we
introduce the idea of extending original temporal centrality metrics by cloning
graphs of an incomplete graph sequence. Focusing on temporal betweenness
centrality as an example, we show for different simulated scenarios of incomplete
graph sequences that our approach improves the accuracy of detecting important
vertices in dynamic networks compared to the original methods. An age-related
gene expression data set from the human brain illustrates the new measures.
Additional results for the temporal closeness centrality based on cloned
snapshots support our findings. We further introduce a new algorithm called REN
to calculate temporal centrality measures. Its computational effort is linear in
the number of snapshots and benefits from sparse or very dense dynamic networks.
CONCLUSIONS: We suggest to use clone temporal centrality measures in incomplete
graph sequences settings. Compared to approaches that do not compensate for
incompleteness our approach will improve the detection rate of important
vertices. The proposed REN algorithm allows to calculate (clone) temporal
centrality measures even for long snapshot sequences.
PMID- 28511666
TI - Barriers and facilitators of access to maternal services for women with
disabilities: scoping review protocol.
AB - BACKGROUND: The Sustainable Development Goals (SDGs) emphasises the increasing
equitable coverage of quality health care and provision of integrated services as
means of reducing maternal mortality. Despite so much effort being placed on
improved access to maternity health care, studies show that women with
disabilities are being systemically excluded from the mainstream maternal health
services. The proposed scoping review aims to map literature on the barriers and
facilitators of access to maternal services for women with disabilities. METHODS
AND ANALYSIS: The search strategy for this scoping review study will involve
electronic databases including Pubmed, MEDLINE via EBSCOhost, CINAHL Plus with
full text via EBSCOhost, Africa-Wide Info via EBSCOhost, JSTOR and Proquest
Health and Medical Complete. Articles will also be searched through the "Cited
by" search as well as citations included in the reference lists of included
articles. A two-stage mapping strategy would be conducted. Stage 1 would be to
screen studies through examining their titles. Furthermore, we will screen
abstracts of the identified studies descriptively and by focus and method as
stipulated by the inclusion and exclusion criteria. In stage 2, we will extract
data from the included studies. A parallel screening and data extraction will be
undertaken by two reviewers. We will access the quality of the included studies
using the mixed methods appraisal tool (MMAT). We will use NVIVO version 10 to
extract the relevant outcomes and thematic analysis of the studies. DISCUSSION:
We anticipate to find relevant studies reporting evidence on the barriers and
facilitators of access to maternal health services in Sub-Saharan Africa. The
evidence obtained from the included studies when summarised will help guide
future research. The study findings will be disseminated electronically and in
print. In addition, it will be presented at conferences related to sexual
reproductive health, maternal health care and reproductive health.
PMID- 28511663
TI - Basic fibroblast growth factor reduces scar by inhibiting the differentiation of
epidermal stem cells to myofibroblasts via the Notch1/Jagged1 pathway.
AB - BACKGROUND: Basic fibroblast growth factor (bFGF) plays an important role in
promoting wound healing and reducing scar, but the possible molecular mechanisms
are still unclear. Our previous studies have found that activating the
Notch1/Jagged1 pathway can inhibit the differentiation of epidermal stem cells
(ESCs) to myofibroblasts (MFB). Herein, we document that bFGF reduces scar by
inhibiting the differentiation of ESCs to MFB via activating the Notch1/Jagged1
pathway. METHODS: In in-vitro study, ESCs were isolated from 10 neonatal SD rats
(1-3 days old), cultured in keratinocyte serum-free medium, and divided into six
groups: bFGF group, bFGF + SU5402 group, bFGF + DAPT group, siJagged1 group, bFGF
+ siJagged1 group, and control group. Jagged1 of the ESCs in the siJagged1 group
and bFGF + siJagged1 group was knocked down by small-interfering RNA
transfection. Expression of ESC markers (CK15/CK10), MFB markers (alpha-SMA,
Collagen I, Collagen III), and Notch1/Jagged1 components (Jagged1, Notch1, Hes1)
was detected by FCM, qRT-PCR, and western blot analysis to study the
relationships of bFGF, ESCs, and Notch1/Jagged1 pathway. In in-vivo study, the
wound healing time and scar hyperplasia were observed on rabbit ear scar models.
The quality of wound healing was estimated by hematoxylin and eosin staining and
Masson staining. Expression of ESC markers, MFB markers and Notch1/Jagged1
components was elucidated by immunohistochemistry, immunofluorescence, and
western blot analysis. RESULTS: The in-vitro study showed that bFGF could
significantly upregulate the expression of ESC markers and Notch1/Jagged1
components, while downregulating the expression of MFB markers at the same time.
However, these effects could be obviously decreased when we knocked down Jagged1
or added DAPT. Similarly, in in-vivo study, bFGF also exhibited its functions in
inhibiting the differentiation of rabbit ESCs to MFB by activating the
Notch1/Jagged1 pathway, which improved the wound healing quality and alleviated
scar significantly. CONCLUSION: These results provide evidence that bFGF can
reduce scar by inhibiting the differentiation of ESCs to MFB via the
Notch1/Jagged1 pathway, and present a new promising potential direction for the
treatment of scar.
PMID- 28511664
TI - Yields and chondrogenic potential of primary synovial mesenchymal stem cells are
comparable between rheumatoid arthritis and osteoarthritis patients.
AB - BACKGROUND: Mesenchymal stem cells derived from the synovial membrane (synovial
MSCs) are a candidate cell source for regenerative medicine of cartilage and
menisci due to their high chondrogenic ability. Regenerative medicine can be
expected for RA patients with the inflammation well-controlled as well as OA
patients and transplantation of synovial MSCs would also be a possible
therapeutic treatment. Some properties of synovial MSCs vary dependent on the
diseases patients have, and whether or not the pathological condition of RA
affects the chondrogenesis of synovial MSCs remains controversial. The purpose of
this study was to compare the properties of primary synovial MSCs between RA and
OA patients. METHODS: Human synovial tissue was harvested during total knee
arthroplasty from the knee joints of eight patients with RA and OA respectively.
Synovial nucleated cells were cultured for 14 days. Total cell yields, surface
markers, and differentiation potentials were analyzed for primary synovial MSCs.
RESULTS: Nucleated cell number per 1 mg synovium was 8.4 +/- 3.9 thousand in RA
and 8.0 +/- 0.9 thousand in OA. Total cell number after 14-day culture/1 mg
synovium was 0.7 +/- 0.4 million in RA and 0.5 +/- 0.3 million in OA, showing no
significant difference between in RA and OA. Cells after 14-day culture were
mostly positive for CD44, CD73, CD90, CD105, negative for CD45 both in RA and OA.
There was no significant difference for the cartilage pellet weight and sGAG
content per pellet between in RA and OA. Both oil red O-positive colony rate and
alizarin red-positive colony rate were similar in RA and OA. CONCLUSIONS: Yields,
surface markers and chondrogenic potential of primary synovial MSCs in RA were
comparable to those in OA. Synovium derived from RA patients can be the cell
source of MSCs for cartilage and meniscus regeneration.
PMID- 28511667
TI - Epidemiology of pertussis in Casablanca (Morocco): contribution of conventional
and molecular diagnosis tools.
AB - BACKGROUND: Pertussis, a vaccine preventable disease, is still responsible of
significant morbidity and mortality around the world, mostly in newborns. The aim
of the present study was (1) to introduce pertussis surveillance in the major
pediatric hospital of Casablanca (2) to analyze the prevalence of pertussis among
children under 14 years of age and their entourage in Casablanca, Morocco.
METHODS: This is a prospective and non-case controlled study, including children
suspected of Pertussis admitted at the Abderrahim Harouchi Pediatric Hospital in
Casablanca, from January 2013 to June 2015. Nasopharyngeal samples were obtained
for Bordetella spp. culture and Real time PCR detection (RT-PCR) with specific
primers of Bordetella spp., B. pertussis, B. parapertussis and B. holmesii. The
detection of Bordetella spp. was also performed in some household contacts of the
children suspected of pertussis. RESULTS: During the 2.5-years period, a total of
282 samples were collected from hospitalized children (156) and in some of their
contacts (126). Among 156 samples from the children (from whom 57% were under 2
month of age), Bordetella DNA was detected in 61% (96/156) by RT-PCR. Among these
positive samples, 91.7% (88/96) corresponded to B. pertussis DNA. Furthermore, in
39.5% (38/96) of the Bordetella positive samples, B. holmesii DNA was also
detected. B. parapertussis DNA was detected in only one sample (1/156). Out of
the 156 samples collected from the hospitalized children, only 48 were tested by
culture, and 4 B. pertussis were isolated (8.3%). Among the 126 samples from the
contacts of the children, mostly mothers (115 cases), Bordetella DNA was detected
in 47% (59/126), 90% (53/59) being B. pertussis DNA. Moreover, B. holmesii DNA
was also detected in 18.6% (11/59) of the Bordetella positive samples, and
coexistence of B. pertussis and B. holmesii DNA in 36.5% (35/96). Two B.
pertussis were isolated by culture performed on 43 samples of the contacts of the
children (4.6%). CONCLUSIONS: This study highlights the circulation of B.
pertussis but also of B. holmesii in Casablanca-Morocco with a high proportion of
co-infections B. holmesii/B. pertussis in infants and their mothers, indicate
that infection of non-vaccinated infants could be more associated with young
parents. Moreover, the RT- PCR provides a sensitive and specific diagnosis of B.
pertussis infections and distinguishes it from other Bordetella species, and is
therefore suitable for implementation in the diagnostic laboratory.
PMID- 28511668
TI - Structural similarities and functional differences clarify evolutionary
relationships between tRNA healing enzymes and the myelin enzyme CNPase.
AB - BACKGROUND: Eukaryotic tRNA splicing is an essential process in the
transformation of a primary tRNA transcript into a mature functional tRNA
molecule. 5'-phosphate ligation involves two steps: a healing reaction catalyzed
by polynucleotide kinase (PNK) in association with cyclic phosphodiesterase
(CPDase), and a sealing reaction catalyzed by an RNA ligase. The enzymes that
catalyze tRNA healing in yeast and higher eukaryotes are homologous to the
members of the 2H phosphoesterase superfamily, in particular to the vertebrate
myelin enzyme 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase). RESULTS: We
employed different biophysical and biochemical methods to elucidate the overall
structural and functional features of the tRNA healing enzymes yeast Trl1
PNK/CPDase and lancelet PNK/CPDase and compared them with vertebrate CNPase. The
yeast and the lancelet enzymes have cyclic phosphodiesterase and polynucleotide
kinase activity, while vertebrate CNPase lacks PNK activity. In addition, we also
show that the healing enzymes are structurally similar to the vertebrate CNPase
by applying synchrotron radiation circular dichroism spectroscopy and small-angle
X-ray scattering. CONCLUSIONS: We provide a structural analysis of the tRNA
healing enzyme PNK and CPDase domains together. Our results support evolution of
vertebrate CNPase from tRNA healing enzymes with a loss of function at its N
terminal PNK-like domain.
PMID- 28511669
TI - Fasting levels of growth hormone are associated with carotid intima media
thickness but are not affected by fluvastatin treatment.
AB - BACKGROUND: Growth hormone (GH) has been linked to cardiovascular disease but the
exact mechanism of this association is still unclear. We here test if the fasting
levels of GH are cross-sectionally associated with carotid intima media thickness
(IMT) and whether treatment with fluvastatin affects the fasting level of GH.
METHODS: We examined the association between GH and IMT in 4425 individuals (aged
46-68 years) included in the baseline examination (1991-1994) of the Malmo Diet
and Cancer cardiovascular cohort (MDC-CC). From that cohort we then studied 472
individuals (aged 50-70 years) who also participated (1994-1999) in the beta
Blocker Cholesterol-Lowering Asymptomatic Plaque Study (BCAPS), a randomized,
double blind, placebo-controlled, single-center clinical trial. Using
multivariate linear regression models we related the change in GH-levels at 12
months compared with baseline to treatment with 40 mg fluvastatin once daily.
RESULTS: In MDC-CC fasting values of GH exhibited a positive cross-sectional
relation to the IMT at the carotid bulb independent of traditional cardiovascular
risk factors (p = 0.002). In a gender-stratified analysis the correlation were
significant for males (p = 0.005), but not for females (p = 0.09). Treatment with
fluvastatin was associated with a minor reduction in the fasting levels of hs-GH
in males (p = 0.05) and a minor rise in the same levels among females (p = 0.05).
CONCLUSIONS: We here demonstrate that higher fasting levels of GH are associated
with thicker IMT in the carotid bulb in males. Treatment with fluvastatin for 12
months only had a minor, and probably not clinically relevant, effect on the
fasting levels of hs-GH.
PMID- 28511671
TI - Erratum to: Investigation of the association between the TCF7L2 rs7903146 (C/T)
gene polymorphism and obesity in a Cameroonian population: a pilot study.
PMID- 28511670
TI - Onco-testicular sperm extraction (onco-TESE) for bilateral testicular tumors: two
case reports.
AB - BACKGROUND: Most patients with testicular cancer are infertile; thus, the
preservation of the sperm after surgery is an important factor to consider. We
report two cases of bilateral testicular cancer in patients who underwent
bilateral higher orchiectomy and simultaneous testicular sperm extraction. CASE
PRESENTATION: Two Asian-Japanese men were referred to our hospital with bilateral
testicular tumors. Both of the patients were preoperatively diagnosed with
azoospermia and requested testicular sperm extraction at the time of higher
orchiectomy. In one patient, sperm was successfully harvested and then frozen. In
the other patient, sperm could not be retrieved from the patient's testis. In
both patients, the pathological diagnosis was seminoma. Testicular tumors often
occur in patients of reproductive age. The preservation of sperm before
chemotherapy or bilateral orchiectomy is necessary for patients with testicular
tumors who wish to be fathers. CONCLUSIONS: Onco-testicular sperm extraction
might be an option for patients with testicular cancer and azoospermia or severe
oligospermia.
PMID- 28511672
TI - CrMAPK3 regulates the expression of iron-deficiency-responsive genes in
Chlamydomonas reinhardtii.
AB - BACKGROUND: Under iron-deficient conditions, Chlamydomonas exhibits high affinity
for iron absorption. Nevertheless, the response, transmission, and regulation of
downstream gene expression in algae cells have not to be investigated.
Considering that the MAPK pathway is essential for abiotic stress responses, we
determined whether this pathway is involved in iron deficiency signal
transduction in Chlamydomonas. RESULTS: Arabidopsis MAPK gene sequences were used
as entry data to search for homologous genes in Chlamydomonas reinhardtii genome
database to investigate the functions of mitogen-activated protein kinase (MAPK)
gene family in C. reinhardtii under iron-free conditions. Results revealed 16 C.
reinhardtii MAPK genes labeled CrMAPK2-CrMAPK17 with TXY conserved domains and
low homology to MAPK in yeast, Arabidopsis, and humans. The expression levels of
these genes were then analyzed through qRT-PCR and exposure to high salt (150 mM
NaCl), low nitrogen, or iron-free conditions. The expression levels of these
genes were also subjected to adverse stress conditions. The mRNA levels of
CrMAPK2, CrMAPK3, CrMAPK4, CrMAPK5, CrMAPK6, CrMAPK8, CrMAPK9, and CrMAPK11 were
remarkably upregulated under iron-deficient stress. The increase in CrMAPK3
expression was 43-fold greater than that in the control. An RNA interference
vector was constructed and transformed into C. reinhardtii 2A38, an algal strain
with an exogenous FOX1:ARS chimeric gene, to silence CrMAPK3. After this gene was
silenced, the mRNA levels and ARS activities of FOX1:ARS chimeric gene and
endogenous CrFOX1 were decreased. The mRNA levels of iron-responsive genes, such
as CrNRAMP2, CrATX1, CrFTR1, and CrFEA1, were also remarkably reduced.
CONCLUSION: CrMAPK3 regulates the expression of iron-deficiency-responsive genes
in C. reinhardtii.
PMID- 28511674
TI - Predictors of fifty days in-hospital mortality in patients with culture negative
neutrocytic ascites.
AB - BACKGROUND: Culture negative neutrocytic ascites is a variant of spontaneous
bacterial peritonitis. But there are conflicting reports regarding the mortality
associated with culture negativeneutrocytic ascites. Therefore we aim to
determine the predictors of mortality associated with culture negativeneutrocytic
ascites in a larger sample population. METHODS: We analysed 170 patients
consecutively admitted to intensive care unit with diagnosis of culture negative
neutrocytic ascites. The clinical, laboratory parameters, etiology of liver
cirrhosis was determined along with the scores like model for end stage liver
disease, child turcotte pugh were recorded. RESULTS: The 50 day in-hospital
mortality rate in culture negative neutrocytic ascites was 39.41% (n = 67). In
univariate analysis, means of parameters like total leucocyte count, urea,
bilirubin, alanine transaminase, aspartate transaminase, international normalized
ratio, acute kidney injury, septic shock, hepatic encephalopathy and model for
end stage liver disease were significantly different among survived and those who
died (P value <=0.05). Cox proportional regression model showed the hazard ratio
(HR) of acute kidney injury was 2.212 (95% CI: 1.334-3.667), septic shock (HR =
1.895, 95% CI: 1.081-3.323) and model for end stage liver disease (HR = 1.054,
95% CI: 1.020-1.090). Receiver operating characteristics curve showed aspartate
aminotransferase (AST) had highest area under the curve 0.761 (95% CI: 0.625
0.785). CONCLUSION: Patients with culture negative neutrocytic ascites have a
mortality rate comparable to spontaneous bacterial peritonitis. aspartate
aminotransferase, alanine aminotransferase (ALT), acute kidney injury (AKI),
model for end stage liver disease (MELD) and septic shock are the independent
predictors of 50 days in-hospital mortality in culture negative neutrocytic
ascites.
PMID- 28511673
TI - Long-term safety and efficacy of vismodegib in patients with advanced basal cell
carcinoma: final update of the pivotal ERIVANCE BCC study.
AB - BACKGROUND: In the primary analysis of the ERIVANCE BCC trial, vismodegib, the
first US Food and Drug Administration-approved Hedgehog pathway inhibitor, showed
objective response rates (ORRs) by independent review facility (IRF) of 30% and
43% in metastatic basal cell carcinoma (mBCC) and locally advanced BCC (laBCC),
respectively. ORRs by investigator review were 45% (mBCC) and 60% (laBCC).
Herein, we present long-term safety and final investigator-assessed efficacy
results in patients with mBCC or laBCC. METHODS: One hundred four patients with
measurable advanced BCC received oral vismodegib 150 mg once daily until disease
progression or intolerable toxicity. The primary end point was IRF-assessed ORR.
Secondary end points included ORR, duration of response (DOR), progression-free
survival, overall survival (OS), and safety. RESULTS: At data cutoff (39 months
after completion of accrual), 8 patients were receiving the study drug (69
patients in survival follow-up). Investigator-assessed ORR was 48.5% in the mBCC
group (all partial responses) and 60.3% in the laBCC group (20 patients had
complete response and 18 patients had partial response). ORRs were comparable
across patient subgroups, including aggressive histologic subtypes (eg,
infiltrative BCC). Median DOR was 14.8 months (mBCC) and 26.2 months (laBCC).
Median OS was 33.4 months in the mBCC cohort and not estimable in the laBCC
cohort. Adverse events remained consistent with clinical experience. Thirty-three
deaths (31.7%) were reported; none were related to vismodegib. CONCLUSIONS: This
long-term update of the ERIVANCE BCC trial demonstrated durability of response,
efficacy across patient subgroups, and manageable long-term safety of vismodegib
in patients with advanced BCC. TRIAL REGISTRATION: This study was registered
prospectively with Clinicaltrials.gov , number NCT00833417 on January 30, 2009.
PMID- 28511676
TI - Physical therapists and importance of work participation in patients with
musculoskeletal disorders: a focus group study.
AB - BACKGROUND: Musculoskeletal disorders are a major health problem resulting in
negative effects on wellbeing and substantial costs to society. Work
participation is associated with positive benefits for both mental and physical
health. Potentially, generalist physical therapists (GPTs) can play an important
role in reducing absenteeism, presenteeism and associated costs in patients with
musculoskeletal disorders. However, work participation is often insufficiently
addressed within generalist physical therapy practice (GPTP). Therefore, this
study evaluates whether GPTs take work participation into account as a
determining factor in patients with musculoskeletal disorders, and how this might
be improved. METHODS: This qualitative study consisted of seven focus groups
involving 30 participants: 21 GPTs and 9 occupational physical therapists (OPTs).
Based on an interview guide, participants were asked how they integrate work
participation within their practice, how they collaborate with other
professionals, and how GPTs can improve integration of the patient's work within
their practice. RESULTS: Although participants recognized the importance of work
participation, they mentioned that the integration of this item in their GPTP
could be improved. Generally, GPTs place insufficient priority on work
participation. Moreover, there is a lack of cooperation between the generalist
physical therapist and (other) occupational healthcare providers (including
OPTs), and the borderlines/differences between generalist physcial therapy and
occupational health physcial therapy were sometimes unclear. GPTs showed a lack
of knowledge and a need for additional information about several important work
related factors (e.g. work content, physical and psychosocial working conditions,
terms of employment). CONCLUSIONS: Although a patient's work is important, GPTs
take insufficient account of work participation as a determining factor in the
treatment of patients with musculoskeletal disorders. GPTs often lack specific
knowledge about work-related factors, and there is insufficient cooperation
between OPTs and other occupational healthcare providers. The integration of work
participation within GPTP, and the cooperation between GPTs and other
occupational healthcare providers, show room for improvement.
PMID- 28511675
TI - Comparing adult renal stem cell identification, characterization and
applications.
AB - Despite growing interest and effort, a consensus has yet to be reached in regards
to the identification of adult renal stem cells. Organ complexity and low
turnover of renal cells has made stem cell identification difficult and lead to
the investigation of multiple possible populations. In this review, we summarize
the work that has been done toward finding and characterizing an adult renal stem
cell population. In addition to giving a general overview of what has been done,
we aim to highlight the variation in methods and outcomes. The methods used to
locate potential stem cell populations can vary widely, but even within the
relatively standard practice of BrdU labeling of slowly dividing cells, there are
significant differences in protocols and results. Additional diversity exists in
cell marker profiles and apparent differentiation potential seen in potential
stem cell sources. Cataloging the variety of methods and outcomes seen so far may
help to streamline future investigation and stear the field toward consensus. But
even without firmly defined populations, the application of renal stem cells
holds tantalizing potential. Populations of highly proliferative, multipotent
cells of renal origin show the ability to engraft in injured kidneys, mitigate
functional loss and occasionally show the ability to generate nephrons de novo.
The progress toward regenerative medicine applications is also summarized.
PMID- 28511677
TI - A strategy to improve phasing of whole-genome sequenced individuals through
integration of familial information from dense genotype panels.
AB - BACKGROUND: Haplotype reconstruction (phasing) is an essential step in many
applications, including imputation and genomic selection. The best phasing
methods rely on both familial and linkage disequilibrium (LD) information. With
whole-genome sequence (WGS) data, relatively small samples of reference
individuals are generally sequenced due to prohibitive sequencing costs, thus
only a limited amount of familial information is available. However, reference
individuals have many relatives that have been genotyped (at lower density). The
goal of our study was to improve phasing of WGS data by integrating familial
information from haplotypes that were obtained from a larger genotyped dataset
and to quantify its impact on imputation accuracy. RESULTS: Aligning a pre-phased
WGS panel [~5 million single nucleotide polymorphisms (SNPs)], which is based on
LD information only, to a 50k SNP array that is phased with both LD and familial
information (called scaffold) resulted in correctly assigning parental origin for
99.62% of the WGS SNPs, their phase being determined unambiguously based on
parental genotypes. Without using the 50k haplotypes as scaffold, that value
dropped as expected to 50%. Correctly phased segments were on average longer
after alignment to the genotype phase while the number of switches decreased
slightly. Most of the incorrectly assigned segments, and subsequent switches,
were due to singleton errors. Imputation from 50k SNP array to WGS data with
improved phasing had a marginal impact on imputation accuracy (measured as r 2),
i.e. on average, 90.47% with traditional techniques versus 90.65% with pre
phasing integrating familial information. Differences were larger for SNPs
located in chromosome ends and rare variants. Using a denser WGS panel (~13
millions SNPs) that was obtained with traditional variant filtering rules, we
found similar results although performances of both phasing and imputation
accuracy were lower. CONCLUSIONS: We present a phasing strategy for WGS data,
which indirectly integrates familial information by aligning WGS haplotypes that
are pre-phased with LD information only on haplotypes obtained with genotyping
data, with both LD and familial information and on a much larger population. This
strategy results in very few mismatches with the phase obtained by Mendelian
segregation rules. Finally, we propose a strategy to further improve phasing
accuracy based on haplotype clusters obtained with genotyping data.
PMID- 28511678
TI - Multidimensional daily diary of fatigue-fibromyalgia-17 items (MDF-fibro-17).
part 1: development and content validity.
AB - BACKGROUND: Fibromyalgia (FM), a disorder characterized by chronic widespread
pain and tenderness, affects greater than five million individuals in the United
States alone. Patients experience multiple symptoms in addition to pain, and
among them, fatigue is one of the most bothersome and disabling. There is a
growing body of literature suggesting that fatigue is a multidimensional concept.
Currently, to our knowledge, no multidimensional Patient Reported Outcome (PRO)
measure of FM-related fatigue meets Food and Drug Administration (FDA)
requirements to support a product label claim. Therefore, the objective of this
research was to evaluate qualitative and quantitative data previously gathered to
inform the development of a comprehensive, multidimensional, PRO measure to
assess FM-related fatigue in FM clinical trials. METHODS: Existing qualitative
and quantitative data from three previously conducted studies in patients with FM
were reviewed to inform the initial development of a multidimensional PRO measure
of FM-related fatigue: 1) a concept elicitation study involving in-depth, open
ended interviews with patients with FM in the United States (US) (N = 20),
Germany (N = 10), and France (N = 10); 2) a cognitive debriefing and pilot study
of a preliminary pool of 23 items (N = 20 US patients with FM); and 3) a
methodology study that explored initial psychometrics of the item pool (N = 145
US patients with FM). RESULTS: Five domains were identified that intend to
capture the broad experience of FM-related fatigue reported in the qualitative
research: the Global Fatigue Experience, Cognitive Fatigue, Physical Fatigue,
Motivation, and Impact on Function. Seventeen of the original pool of 23 items
were selected to best capture these five dimensions. These 17 items formed the
basis of a newly developed multidimensional PRO measure to assess FM-related
fatigue in clinical trials: the Multidimensional Daily Diary of Fatigue
Fibromyalgia-17 (MDF-Fibro-17). CONCLUSION: Qualitative analysis, and preliminary
quantitative item level data, confirmed that FM-related fatigue is
multidimensional and provided strong support for the content validity of the MDF
Fibro-17. The next stage was to quantitatively evaluate the measure to confirm
the factor structure, psychometric properties, sensitivity to change, and
meaningful change. This has been conducted and is being reported separately.
PMID- 28511679
TI - Evaluation of anti-inflammatory and gastric anti-ulcer activity of Phyllanthus
niruri L. (Euphorbiaceae) leaves in experimental rats.
AB - BACKGROUND: The medicinal plants signify a massive basin of potential
phytoconstituents that could be valuable as a substitute to allopathic drugs or
considered as an analogue in drug development. Phyllanthus niruri L.
(Euphorbiaceae) is generally used in traditional medicine to treat ulcer and
inflammation. In this project we investigated the methanolic extract of leaves of
Phyllanthus niruri for anti-inflammatory and anti-ulcer activity. METHODS: The
anti-inflammatory activity of methanol extract of Phyllanthus niruri leaves was
evaluated at the doses of 100, 200 and 400 mg/kg, p.o. while using ibuprofen (20
mg/kg, p.o) as the standard drug. The animals used were Swiss albino rats.
Inflammation was induced by injecting 0.1 ml carrageenan (1% w/v) into the left
hind paw. Paw tissues from the different groups were examined for inflammatory
cell infiltration. On the other hand, antiulcer activity of methanolic extract of
P. niruri leaves at the doses of 100, 200 and 400 mg/kg, p.o. were examined
against ethanol-acid induced gastric mucosal injury in the Swiss albino rats -
keeping omeprazole (20 mg/kg, p.o.) as reference. The rats were dissected and the
stomachs were macroscopically examined to identify hemorrhagic lesions in the
glandular mucosa. RESULTS: P. niruri significantly (p < 0.01) decreased
carrageenan-induced paw edema; it exhibited a reduction of 46.80%, 55.32% and
69.14% at doses of 100, 200 and 400 mg/kg, respectively. These findings were
further supported by the histological study. The methanolic extract also
disclosed good protective effect against ethanol-acid induced gastric mucosal
injury in the rats. Administration of the extract's doses (100, 200 and 400
mg/kg) demonstrated a significant (p < 0.01) reduction in the ethanol- acid
induced gastric erosion in all the experimental groups when compared to the
control. The methanolic extract at the higher dose (400 mg/kg) resulted in better
inhibition of ethanol-acid induced gastric ulcer as compare to omeprazole (20
mg/kg). Histological studies of the gastric wall revealed that toxic control rats
revealed mucosal degeneration, ulceration and migration of numerous inflammatory
cells throughout the section. On the other hand, MEPN treatment groups showed
significant regeneration of mucosal layer and significantly prevented the
formation of hemorrhage and edema. CONCLUSIONS: The investigation suggests that
methanolic extract of P. niruri leaf possess anti-inflammatory activity and
promotes ulcer protection as ascertained by regeneration of mucosal layer and
substantial prevention of the formation of hemorrhage and edema.
PMID- 28511680
TI - Cohort profile: seek, test, treat and retain United States criminal justice
cohort.
AB - BACKGROUND: The STTR treatment cascade provides a framework for research aimed at
improving the delivery of services, care and outcomes of PLWH. The development of
effective approaches to increase HIV diagnoses and engage PLWH in subsequent
steps of the treatment cascade could lead to earlier and sustained ART treatment
resulting in viral suppression. There is an unmet need for research applying the
treatment cascade to improve outcomes for those with criminal justice
involvement. METHODS: The Seek, Test, Treat, and Retain (STTR) criminal justice
(CJ) cohort combines data from 11 studies across the HIV treatment cascade that
focused on persons involved in the criminal justice system, often but not
exclusively for reasons related to substance use. The studies were conducted in a
variety of CJ settings and collected information across 11 pre-selected domains:
demographic characteristics, CJ involvement, HIV risk behaviors, HIV and/or
Hepatitis C infections, laboratory measures of CD4 T-cell count (CD4) and HIV RNA
viral load (VL), mental illness, health related quality of life (QoL),
socioeconomic status, health care access, substance use, and social support.
RESULTS: The STTR CJ cohort includes data on 11,070 individuals with and without
HIV infection who range in age from 18 to 77 years, with a median age at baseline
of 37 years. The cohort reflects racial, ethnic and gender distributions in the
U.S. CJ system, and 64% of participants are African-American, 12% are Hispanic
and 83% are men. Cohort members reported a wide range of HIV risk behaviors
including history of injection drug use and, among those who reported on pre
incarceration sexual behaviors, the prevalence of unprotected sexual intercourse
ranged across studies from 4% to 79%. Across all studies, 53% percent of the STTR
CJ cohort reported recent polysubstance use. CONCLUSIONS: The STTR CJ cohort is
comprised of participants from a wide range of CJ settings including jail,
prison, and community supervision who report considerable diversity in their
characteristics and behavioral practices. We have developed harmonized measures,
where feasible, to improve the integration of these studies together to answer
questions that cannot otherwise be addressed.
PMID- 28511681
TI - Chromosome engineering of Escherichia coli for constitutive production of
salvianic acid A.
AB - BACKGROUND: Salvianic acid A (SAA), a valuable natural product from herbal plant
Salvia miltiorrhiza, exhibits excellent antioxidant activities on food industries
and efficacious therapeutic potential on cardiovascular diseases. Recently,
production of SAA in engineered Escherichia coli was established via the
artificial biosynthetic pathway of SAA on the multiple plasmids in our previous
work. However, the plasmid-mediated system required to supplement expensive
inducers and antibiotics during the fermentation process, restricting scale-up
production of SAA. Microbial cell factory would be an attractive approach for
constitutive production of SAA by chromosome engineering. RESULTS: The limited
enzymatic reactions in SAA biosynthetic pathway from glucose were grouped into
three modules, which were sequentially integrated into chromosome of engineered
E. coli by lambda Red homologous recombination method. With starting strain E.
coli BAK5, in which the ptsG, pykF, pykA, pheA and tyrR genes were previously
deleted, chassis strain BAK11 was constructed for constitutive production of
precursor L-tyrosine by replacing the 17.7-kb mao-paa cluster with module 1 (P
lacUV5 -aroG fbr -tyrA fbr -aroE) and the lacI gene with module 2 (P trc -glk
tktA-ppsA). The synthetic 5tacs promoter demonstrated the optimal strength to
drive the expression of hpaBC-d-ldh Y52A in module 3, which then was inserted at
the position between nupG and speC on the chromosome of strain BAK11. The final
strain BKD13 produced 5.6 g/L of SAA by fed-batch fermentation in 60 h from
glucose without any antibiotics and inducers supplemented. CONCLUSIONS: The
plasmid-free and inducer-free strain for SAA production was developed by targeted
integration of the constitutive expression of SAA biosynthetic genes into E. coli
chromosome. Our work provides the industrial potential for constitutive
production of SAA by the indel microbial cell factory and also sets an example of
further producing other valuable natural and unnatural products.
PMID- 28511682
TI - Inequities in coverage of smokefree space policies within the United States.
AB - BACKGROUND: Previous studies have found extensive geographic and demographic
differences in tobacco use. These differences have been found to be reduced by
effective public policies, including banning smoking in public spaces. Smokefree
indoor and outdoor spaces reduce secondhand smoke exposure and denormalize
smoking. METHODS: We evaluated regional and demographic differences in the
proportion of the population covered by smokefree policies enacted in the United
States prior to 2014, for both adults and children. RESULTS: Significant
differences in coverage were found by ethnicity, region, income, and education (p
< 0.001). Smokefree policy coverage was lower for jurisdictions with higher
proportions of poor households, households with no high school diploma and the
Southeast region. Increased ethnic heterogeneity was found to be a significant
predictor of coverage in indoor "public spaces generally", meaning that diversity
is protective, with differential effect by region (p = 0.004) - which may relate
to urbanicity. Children had a low level of protection in playgrounds and schools
(~10% covered nationwide) - these spaces were found to be covered at lower rates
than indoor spaces. CONCLUSIONS: Disparities in smokefree space policies have
potential to exacerbate existing health inequities. A national increase in
smokefree policies to protect children in playgrounds and schools is a crucial
intervention to reduce such inequities.
PMID- 28511683
TI - Acute coronary syndrome patients admitted to a cardiology vs non-cardiology
service: variations in treatment & outcome.
AB - BACKGROUND: Specialized cardiology services have contributed to reduced mortality
in acute coronary syndromes (ACS). We sought to evaluate the outcomes of ACS
patients admitted to non-cardiology services in Southern Alberta. METHODS:
Retrospective chart review performed on all troponin-positive patients in the
Calgary Health Region identified those diagnosed with ACS by their attending
team. Patients admitted to non-cardiology and cardiology services were compared,
using linked data from the Alberta Provincial Project for Outcomes Assessment in
Coronary Heart Disease (APPROACH) registry and the Strategic Clinical Network for
Cardiovascular Health and Stroke. RESULTS: From January 1, 2007 to December 31,
2008, 2105 ACS patients were identified, with 1636 (77.7%) admitted to cardiology
and 469 (22.3%) to non-cardiology services. Patients admitted to non-cardiology
services were older, had more comorbidities, and rarely received cardiology
consultation (5.1%). Cardiac catheterization was underutilized (5.1% vs 86.4% in
cardiology patients (p < 0.0001)), as was evidence-based pharmacotherapy (p <
0.0001). Following adjustment for baseline comorbidities, 30-day through 4-year
mortality was significantly higher on non-cardiology vs. cardiology services
(49.1% vs. 11.0% respectively at 4-years, p < 0.0001). CONCLUSION: In a large ACS
population in the Calgary Health Region, 25% were admitted to non-cardiology
services. These patients had worse outcomes, despite adjustment for baseline risk
factor differences. Although many patients were appropriately admitted to non
cardiology services, the low use of investigations and secondary prevention
medications may contribute to poorer patient outcome. Further research is
required to identify process of care strategies to improve outcomes and lessen
the burden of illness for patients and the health care system.
PMID- 28511684
TI - Access to pediatric rheumatology care for Juvenile Idiopathic Arthritis in the
United Arab Emirates.
AB - BACKGROUND: This study looks at access to care for Juvenile Idiopathic Arthritis
through pediatric rheumatology in the UAE, as an example of multi-ethnic society.
METHODS: Patients with a diagnosis of Juvenile idiopathic arthritis were
identified through the hospital electronic medical records system from January
1st 2011 to December 31st 2014. All residents of the United Arab Emirates hold an
Emirates identity card. We divided our patients into two groups: Emirati
Emirates, who are native Emirati children and hold the Emirati nationality, as
stated on their Emirates identity card, and who therefore have full,
comprehensive access to free medical care; and non-Emirati-Emirates, who
represent other nationalities, as stated on their Emirates identity card. The
primary objective of this study is to look at access to care for Juvenile
idiopathic arthritis through pediatric rheumatology in the two groups. The
secondary objective is to look at the effect of having multiple types of
healthcare insurance coverage on access to biologics. A retrospective review was
carried out. RESULTS: Sixty-six patients with JIA identified: 33 Emirates and 33
non-Emirates. For Emirates, the mean time from onset to first appointment with
pediatric rheumatologist and diagnosis is 9 months (range: 1-48), and for non
Emirates is 12.4 months (range: 1-96). Among the Emirates, 10 patients are
currently on biologic with methotrexate. Among the non-Emirates, 15 are on
biologic with methotrexate. Among the Emirates, 12 are currently in remission
while on treatment, as are 10 non-Emirates. Regarding disability, one Emirati
patient has blindness secondary to noncompliance while under previous treatment.
One Non-Emirati developed joint deformities due to periods of noncompliance and
no follow up. CONCLUSIONS: Delay in presentation to pediatric rheumatology has
been identified as an important factor in our population, which is multi-cultural
and multi-ethnic. Type of health care insurance cover did not affect number of
patients getting biological therapy once patient seen in the pediatric
rheumatology service.
PMID- 28511685
TI - Respectful maternity care in Ethiopian public health facilities.
AB - BACKGROUND: Disrespect and abuse of women during institutional childbirth
services is one of the deterrents to utilization of maternity care services in
Ethiopia and other low- and middle-income countries. This paper describes the
prevalence of respectful maternity care (RMC) and mistreatment of women in
hospitals and health centers, and identifies factors associated with occurrence
of RMC and mistreatment of women during institutional labor and childbirth
services. METHODS: This study had a cross sectional study design. Trained
external observers assessed care provided to 240 women in 28 health centers and
hospitals during labor and childbirth using structured observation checklists.
The outcome variable, providers' RMC performance, was measured by nine behavioral
descriptors. The outcome, any mistreatment, was measured by four items related to
mistreatment of women: physical abuse, verbal abuse, absence of privacy during
examination and abandonment. We present percentages of the nine RMC indicators,
mean score of providers' RMC performance and the adjusted multilevel model
regression coefficients to determine the association with a quality improvement
program and other facility and provider characteristics. RESULTS: Women on
average received 5.9 (66%) of the nine recommended RMC practices. Health centers
demonstrated higher RMC performance than hospitals. At least one form of
mistreatment of women was committed in 36% of the observations (38% in health
centers and 32% in hospitals). Higher likelihood of performing high level of RMC
was found among male vs. female providers ([Formula: see text], p = 0.012),
midwives vs. other cadres ([Formula: see text], p = 0.002), facilities
implementing a quality improvement approach, Standards-based Management and
Recognition (SBM-R(c)) ([Formula: see text], p = 0.003), and among laboring women
accompanied by a companion [Formula: see text], p = 0.003). No factor was
associated with observed mistreatment of women. CONCLUSION: Quality improvement
using SBM-R(c) and having a companion during labor and delivery were associated
with RMC. Policy makers need to consider the role of quality improvement
approaches and accommodating companions in promoting RMC. More research is needed
to identify the reason for superior RMC performance of male providers over female
providers and midwives compared to other professional cadre, as are longitudinal
studies of quality improvement on RMC and mistreatment of women during labor and
childbirth services in public health facilities.
PMID- 28511686
TI - Intrathymic injection of hematopoietic progenitor cells establishes functional T
cell development in a mouse model of severe combined immunodeficiency.
AB - BACKGROUND: Even though hematopoietic stem cell transplantation can be curative
in patients with severe combined immunodeficiency, there is a need for additional
strategies boosting T cell immunity in individuals suffering from genetic
disorders of lymphoid development. Here we show that image-guided intrathymic
injection of hematopoietic stem and progenitor cells in NOD-scid IL2rgammanull
mice is feasible and facilitates the generation of functional T cells conferring
protective immunity. METHODS: Hematopoietic stem and progenitor cells were
isolated from the bone marrow of healthy C57BL/6 mice (wild-type, Luciferase+,
CD45.1+) and injected intravenously or intrathymically into both male and female,
young or aged NOD-scid IL2rgammanull recipients. The in vivo fate of injected
cells was analyzed by bioluminescence imaging and flow cytometry of thymus- and
spleen-derived T cell populations. In addition to T cell reconstitution, we
evaluated mice for evidence of immune dysregulation based on diabetes development
and graft-versus-host disease. T cell immunity following intrathymic injection of
hematopoietic stem and progenitor cells in NOD-scid IL2rgammanull mice was
assessed in a B cell lymphoma model. RESULTS: Despite the small size of the
thymic remnant in NOD-scid IL2rgammanull mice, we were able to accomplish precise
intrathymic delivery of hematopoietic stem and progenitor cells by ultrasound
guided injection. Thymic reconstitution following intrathymic injection of
healthy allogeneic hematopoietic cells was most effective in young male
recipients, indicating that even in the setting of severe immunodeficiency, sex
and age are important variables for thymic function. Allogeneic T cells generated
in intrathymically injected NOD-scid IL2rgammanull mice displayed anti-lymphoma
activity in vivo, but we found no evidence for severe auto/alloreactivity in T
cell-producing NOD-scid IL2rgammanull mice, suggesting that immune dysregulation
is not a major concern. CONCLUSIONS: Our findings suggest that intrathymic
injection of donor hematopoietic stem and progenitor cells is a safe and
effective strategy to establish protective T cell immunity in a mouse model of
severe combined immunodeficiency.
PMID- 28511687
TI - Polymeric micelles with dual thermal and reactive oxygen species (ROS)
responsiveness for inflammatory cancer cell delivery.
AB - BACKGROUND: The object of this study was to develop a thermally and reactive
oxygen species-responsive nanocarrier system for cancer therapy. RESULTS: PPS
PNIPAm block copolymer was designed and synthesised using a combination of living
anionic ring-opening polymerization and atom transfer radical polymerization. The
synthesized polymer formed micellar aggregates in water and demonstrated dual
responsiveness towards temperature and oxidants. Using doxorubicin (DOX) as a
model drug, encapsulation and in vitro release of the drug molecules in PPS
PNIPAm nanocarriers confirmed the responsive release properties of such system.
Cell uptake of the DOX loaded micelles was investigated with human breast cancer
cell line (MCF-7). The results showed Dox-loaded micelles were able to be taken
by the cells and mainly reside in the cytoplasma. In the stimulated cells with an
elevated level of ROS, more released DOX was observed around the nuclei. In the
cytotoxicity experiments, the Dox-loaded micelles demonstrated comparable
efficacy to free DOX at higher concentrations, especially on ROS stimulated
cells. CONCLUSIONS: These results demonstrated that PPS-PNIPAm nanocarriers
possess the capability to respond two typical stimuli in inflammatory cells:
temperature and oxidants and can be used in anticancer drug delivery.
PMID- 28511688
TI - Predictors of adherence to micronutrient supplementation before and during
pregnancy in Vietnam.
AB - BACKGROUND: Poor adherence to micronutrient supplementation often limits the
effectiveness of public health programs. While predictors of adherence to
micronutrient supplementation during pregnancy are well documented, information
on adherence to preconception supplements is scarce. The objective of this study
was to describe the predictors of adherence to preconception and prenatal
micronutrient supplementation among women participating in a randomized control
trial in Vietnam. METHODS: Adherence data were collected prospectively from a
double blind randomized controlled trial in rural Vietnam. Five thousand eleven
women of reproductive age were randomized to receive preconception supplements
for weekly consumption containing either: Folic Acid, Iron and Folic Acid (IFA),
or Multiple Micronutrients. Women who became pregnant received prenatal IFA
supplements for daily consumption through delivery. Village health workers
visited participants' homes every two weeks to deliver supplements and record
consumption and side effects. Multivariate logistic regression was used to assess
individual, household, and programmatic predictors of supplement adherence.
RESULTS: Adherence was high with 78 and 82% of the women consuming more than 80%
of the preconception and prenatal supplements, respectively. Women of minority
ethnicity (OR = 0.78 95% CI = 0.67, 0.91) and farmers (OR = 0.71 95% CI = 0.58,
0.88) were less likely to consume >80% of the preconception supplements while
socioeconomic status (SES) (OR = 2.71 highest vs. lowest quintile; 95% CI = 2.10,
3.52) was positively associated with >80% adherence in the entire preconception
sample with available information (n = 4417). Women in their first pregnancy had
lower prenatal adherence compared to multiparous women. At the programmatic
level, each village health worker visit was associated with higher odds of >80%
adherence by 3-5% before pregnancy and 18% during pregnancy. CONCLUSIONS: Key
determinants of adherence included SES, ethnicity, occupation (farmer) and parity
which may be helpful for targeting women for counseling on supplement adherence.
Increased contact with village health workers was positively associated with
adherence to micronutrient supplementation both before conception and during
pregnancy indicating the need for resources to support community outreach to
women of reproductive age. TRIAL REGISTRATION: NCT01665378 . Registered on August
12, 2012.
PMID- 28511689
TI - Harnessing interactive technologies to improve health outcomes in juvenile
idiopathic arthritis.
AB - BACKGROUND: Children and adolescents with Juvenile Idiopathic Arthritis (JIA)
typically have reduced physical activity level and impaired aerobic and anaerobic
exercise capacity when compared to their non-JIA counterparts. Low intensity
exercise regimens appear to be safe in children with JIA and may results in
improvements in overall physical function. Poor adherence to paediatric
rheumatology treatment may lead to negative clinical outcomes and possibly
increased disease activity. This includes symptoms such as pain, fatigue, quality
of life, longer term outcomes including joint damage, as well as increase of
healthcare associated costs. Low adherence to medications such as methotrexate
and biological-drugs remains a significant issue for paediatric rheumatologists,
with alarming reports that less than half of the children with JIA are compliant
to drug-therapy. MAIN BODY: The recent advances in interactive technology
resulting in a variety of wearable user-friendly smart devices may become a key
solution to address important questions in JIA clinical management. Fully
understanding the impact that arthritis and treatment complications have upon
individual children and their families has long been a challenge for clinicians.
Modern interactive technologies can be customised and accessed directly in the
hands or wrists of children with JIA. These secured networks could be accessible
'live' at anytime and anywhere by the child, parents and clinicians.
Multidisciplinary teams in paediatric rheumatology may benefit from adopting
these technologies to better understand domains such as patient biological
parameters, symptoms progression, adherence to drug-therapy, quality of life, and
participation in physical activities. Most importantly the use of smart devices
technologies may also facilitate more timely clinical decisions, improve self
management and parents awareness in the progression of their child's disease.
Paediatric rheumatology research could also benefit from the use of these smart
devices, as they would allow real-time access to meaningful data to thoroughly
understand the disease-patterns of JIA, such as pain and physical activity
outcomes. Data collection that typically occurs once every 1 or 3 months in the
clinical setting could instead be gathered every week, day, minute or virtually
live online. Arguably, few limitations in wearing such interactive technologies
still exist and require further developments. CONCLUSION: Finally, by embracing
and adapting these new and now highly accessible interactive technologies,
clinical management and research in paediatric rheumatology may be greatly
advanced.
PMID- 28511690
TI - Development of a clinical prediction algorithm for knee osteoarthritis structural
progression in a cohort study: value of adding measurement of subchondral bone
density.
AB - BACKGROUND: Risk prediction algorithms increase understanding of which patients
are at greatest risk of a harmful outcome. Our goal was to create a clinically
useful prediction algorithm for structural progression of knee osteoarthritis
(OA), using medial joint space loss as a proxy; and to quantify the benefit of
including periarticular bone mineral density (BMD) in the algorithm. METHODS:
Participants were from the Osteoarthritis Initiative (OAI) Progression Cohort,
with X-ray readings of medial joint space at 36- and 48-month visits, and a 30-
or 36-month medial-to-lateral tibial BMD ratio (M:L BMD ratio) value. Loss of
medial joint space was the outcome and clinically available factors associated
with OA progression were employed in the base prediction algorithm, with M:L BMD
ratio added to an enhanced prediction algorithm. The benefit of adding M:L BMD
ratio was evaluated by change in area under the ROC curve (AUC), net
reclassification improvement (NRI), and integrated discrimination improvement
(IDI). RESULTS: Five hundred thirty-three participants were included; 51 (14%)
had medial joint space loss; 47% were female; the mean (SD) age was 64.6 (9.2)
years and BMI was 29.6 (4.8) kg/m2. The base algorithm model included age, BMI,
gender, recent injury, knee pain, and hand OA as predictors and had an AUC value
of 0.65. The algorithm adding M:L BMD ratio had an AUC value of 0.73, and the
AUC, NRI and IDI were all significantly improved (p <= 0.002). CONCLUSIONS: This
clinical prediction algorithm predicts structural progression in individuals with
OA using only clinically available predictors supplemented by the M:L BMD ratio,
a biomarker that could be made available at clinical sites.
PMID- 28511691
TI - Tomato root microbiota and Phytophthora parasitica-associated disease.
AB - BACKGROUND: Interactions between pathogenic oomycetes and microbiota residing on
the surface of the host plant root are unknown, despite being critical to
inoculum constitution. The nature of these interactions was explored for the
polyphagous and telluric species Phytophthora parasitica. RESULTS: Composition of
the rhizospheric microbiota of Solanum lycopersicum was characterized using deep
re-sequencing of 16S rRNA gene to analyze tomato roots either free of or partly
covered with P. parasitica biofilm. Colonization of the host root surface by the
oomycete was associated with a shift in microbial community involving a
Bacteroidetes/Proteobacteria transition and Flavobacteriaceae as the most
abundant family. Identification of members of the P. parasitica-associated
microbiota interfering with biology and oomycete infection was carried out by
screening for bacteria able to (i) grow on a P. parasitica extract-based medium
(ii), exhibit in vitro probiotic or antibiotic activity towards the oomycete
(iii), have an impact on the oomycete infection cycle in a tripartite interaction
S. lycopersicum-P. parasitica-bacteria. One Pseudomonas phylotype was found to
exacerbate disease symptoms in tomato plants. The lack of significant gene
expression response of P. parasitica effectors to Pseudomonas suggested that the
increase in plant susceptibility was not associated with an increase in
virulence. Our results reveal that Pseudomonas spp. establishes commensal
interactions with the oomycete. Bacteria preferentially colonize the surface of
the biofilm rather than the roots, so that they can infect plant cells without
any apparent infection of P. parasitica. CONCLUSIONS: The presence of the
pathogenic oomycete P. parasitica in the tomato rhizosphere leads to a shift in
the rhizospheric microbiota composition. It contributes to the habitat extension
of Pseudomonas species mediated through a physical association between the
oomycete and the bacteria.
PMID- 28511692
TI - Vitamin D receptor activation reduces inflammatory cytokines and plasma MicroRNAs
in moderate chronic kidney disease - a randomized trial.
AB - BACKGROUND: Chronic kidney disease (CKD) is a major risk factor for
cardiovascular disease (CVD), partly due to endothelial dysfunction and chronic
inflammation. Vitamin D treatment in end stage renal disease is suggested to
modulate the immune system and lead to improved outcomes. We and others have
demonstrated that treatment with vitamin D or activated vitamin D analogues
protects the endothelial function in less severe renal disease as well. Since the
endothelial protection might be mediated by vitamin D effects on inflammation, we
assessed levels of pro-inflammatory cytokines and micro RNAs (miRs) in patients
with moderate CKD, treated with an active vitamin D analogue (paricalcitol).
METHODS: Thirty-six patients with moderate CKD were randomized to 12 weeks
treatment with placebo, 1 MUg, or 2 MUg paricalcitol daily. Cytokines were
measured by Milliplex 26-plex. Total RNA was isolated from plasma and miRs were
determined by quantitative reverse transcription PCR analysis. RESULTS: Selected
pro-inflammatory cytokines decreased significantly following treatment, while no
change was observed in the placebo group. The micro RNAs; miR 432-5p, miR 495-3p,
and miR 576-5p were significantly downregulated in the active treated groups,
compared to the placebo group. CONCLUSION: Paricalcitol treatment for 12 weeks in
patients with moderate CKD reduces cytokines and micro RNAs involved in
atherosclerosis and inflammation. The potentially protective role of vitamin D
receptor activation in the inflammatory processes regarding the long-term
outcomes in CKD patients warrants further studies. TRIAL REGISTRATION: SOLID
study; NCT01204528 , April 27, 2010.
PMID- 28511693
TI - Antagonistic action on NMDA/GluN2B mediated currents of two peptides that were
conantokin-G structure-based designed.
AB - BACKGROUND: The GluN2B subunit of the N-methyl-D-aspartate receptor (NMDAr)
modulates many physiological processes including learning, memory, and pain.
Excessive increase in NMDAr/GluN2B activity has been associated with various
disorders such neuropathic pain and neuronal death following hypoxia. Thus there
is an interest in identifying NMDAr antagonists that interact specifically with
the GluN2B subunit. Recently based on structural analysis between the GluN2B
subunit and conantokin-G, a toxin that interacts selectively with the GluN2B
subunit, we designed various peptides that are predicted to act as NMDAr
antagonists by interacting with the GluN2B subunit. In this study we tested this
prediction for two of these peptides EAR16 and EAR18. RESULTS: The effects of
EAR16 and EAR18 in NMDA-evoked currents were measured in cultured rat embryonic
hippocampal neurons and in HEK-293 cells expressing recombinant NMDAr comprised
of GluN1a-GluN2A or GluN1a-GluN2B subunits. In hippocampal neurons, EAR16 and
EAR18 reduced the NMDA-evoked calcium currents in a dose-dependent and reversible
manner with comparable IC50 (half maximal inhibitory concentration) values of 241
and 176 uM, respectively. At 500 uM, EAR16 blocked more strongly the NMDA-evoked
currents mediated by the GluN1a-GluN2B (84%) than those mediated by the GluN1a
GluN2A (50%) subunits. At 500 uM, EAR18 blocked to a similar extent the NMDA
evoked currents mediated by the GluN1a-GluN2B (62%) and the GluN1a-GluN2A (55%)
subunits. CONCLUSIONS: The newly designed EAR16 and EAR18 peptides were shown to
block in reversible manner NMDA-evoked currents, and EAR16 showed a stronger
selectivity for GluN2B than for GluN2A.
PMID- 28511695
TI - Absolute and relative accelerometer thresholds for determining the association
between physical activity and metabolic syndrome in the older adults: The
Generation-100 study.
AB - BACKGROUND: When assessing population adherence to physical activity (PA)
recommendation using accelerometers, absolute intensity threshold definition is
applied despite having limited validity in those with low cardiorespiratory
fitness (CRF), who are unable to reach them (e.g older adults). Thus, PA
thresholds relative to CRF may be an alternative approach. We compared the
proportion of the older adults meeting the PA recommendation when PA is assessed
using absolute versus sex-and-CRF-adjusted (relative) accelerometer thresholds
and determined the association between relative versus absolute moderate PA
(MPA), vigorous PA (VPA) and moderate-to-vigorous PA (MVPA) and metabolic
syndrome (MetS). METHODS: Cross-sectional study of 509 men and 567 women aged 70
77. Accelerometer assessed MPA, VPA and MVPA were analyzed using absolute and
relative thresholds. Meeting the PA-recommendation was defined as amounting >=150
min/week in MPA/MVPA or 75 min/week in VPA, respectively. CRF was directly
measured as peak oxygen uptake (VO2peak). MetS was defined as 3 or more of the
following: elevated waist circumference, fasting glucose, hypertension,
triglycerides, decreased HDL-cholesterol or diabetes, dyslipidemia or
hypertension medication. RESULTS: Higher proportion of the population met the
recommendation when PA was assessed with relative compared to absolute
thresholds: VPA (72.4% vs. 1.7%) and MVPA (75.2% vs. 33.8%). Logistic regression
analysis revealed that men and women not meeting the relative-MVPA or VPA
recommendation had higher likelihood of MetS (Men: MVPA OR: 1.59, 95% CI: 1.08
2.33. VPA OR: 1.81, 95%CI: 1.23-2.67 and Women: MVPA OR: 2.12, 95% CI: 1.36-3.31;
VPA OR: 1.95, 95% CI: 1.29-2.95), compared to men and women meeting the relative
MVPA or VPA recommendation. There was no significant association between MetS and
absolute MVPA, MPA or VPA recommendations in the fully adjusted model.
CONCLUSIONS: The association between meeting/not meeting the PA recommendation
and MetS differed with method. Not meeting relative MVPA and VPA recommendation
was associated with significantly higher likelihood for presence of MetS. Since
relative intensity is part of the current PA recommendation, it should be
considered when assessing population PA and associated health risks in the older
adults. TRIAL REGISTRATION: Clinical Trial Registration: NCT01931111 (Date of
trial registration: July 19, 2013).
PMID- 28511694
TI - Ethephon induced oxidative stress in the olive leaf abscission zone enables
development of a selective abscission compound.
AB - BACKGROUND: Table olives (Olea europaea L.), despite their widespread production,
are still harvested manually. The low efficiency of manual harvesting and the
rising costs of labor have reduced the profitability of this crop. A selective
abscission treatment, inducing abscission of fruits but not leaves, is crucial
for the adoption of mechanical harvesting of table olives. In the present work we
studied the anatomical and molecular differences between the three abscission
zones (AZs) of olive fruits and leaves. RESULTS: The fruit abscission zone 3
(FAZ3), located between the fruit and the pedicel, was found to be the active AZ
in mature fruits and is sensitive to ethephon, whereas FAZ2, between the pedicel
and the rachis, is the flower active AZ as well as functioning as the most
ethephon induced fruit AZ. We found anatomical differences between the leaf AZ
(LAZ) and the two FAZs. Unlike the FAZs, the LAZ is characterized by small cells
with less pectin compared to neighboring cells. In an attempt to differentiate
between the fruit and leaf AZs, we examined the effect of treating olive-bearing
trees with ethephon, an ethylene-releasing compound, with or without
antioxidants, on the detachment force (DF) of fruits and leaves 5 days after the
treatment. Ethephon treatment enhanced pectinase activity and reduced DF in all
the three olive AZs. A transcriptomic analysis of the three olive AZs after
ethephon treatment revealed induction of several genes encoding for hormones
(ethylene, auxin and ABA), as well as for several cell wall degrading enzymes.
However, up-regulation of cellulase genes was found only in the LAZ. Many genes
involved in oxidative stress were induced by the ethephon treatment in the LAZ
alone. In addition, we found that reactive oxygen species (ROS) mediated
abscission in response to ethephon only in leaves. Thus, adding antioxidants such
as ascorbic acid or butyric acid to the ethephon inhibited leaf abscission but
enhanced fruit abscission. CONCLUSION: Our findings suggest that treating olive
bearing trees with a combination of ethephon and antioxidants reduces the
detachment force (DF) of fruit without weakening that of the leaves. Hence, this
selective abscission treatment may be used in turn to promote mechanized harvest
of olives.
PMID- 28511696
TI - Variant effect prediction tools assessed using independent, functional assay
based datasets: implications for discovery and diagnostics.
AB - BACKGROUND: Genetic variant effect prediction algorithms are used extensively in
clinical genomics and research to determine the likely consequences of amino acid
substitutions on protein function. It is vital that we better understand their
accuracies and limitations because published performance metrics are confounded
by serious problems of circularity and error propagation. Here, we derive three
independent, functionally determined human mutation datasets, UniFun, BRCA1-DMS
and TP53-TA, and employ them, alongside previously described datasets, to assess
the pre-eminent variant effect prediction tools. RESULTS: Apparent accuracies of
variant effect prediction tools were influenced significantly by the benchmarking
dataset. Benchmarking with the assay-determined datasets UniFun and BRCA1-DMS
yielded areas under the receiver operating characteristic curves in the modest
ranges of 0.52 to 0.63 and 0.54 to 0.75, respectively, considerably lower than
observed for other, potentially more conflicted datasets. CONCLUSIONS: These
results raise concerns about how such algorithms should be employed, particularly
in a clinical setting. Contemporary variant effect prediction tools are unlikely
to be as accurate at the general prediction of functional impacts on proteins as
reported prior. Use of functional assay-based datasets that avoid prior
dependencies promises to be valuable for the ongoing development and accurate
benchmarking of such tools.
PMID- 28511697
TI - Immunohistology and remodeling in fatal pediatric and adolescent asthma.
AB - BACKGROUND: Thickening of reticular basement membrane, increased airway smooth
muscle mass and eosinophilic inflammation are found in adult fatal asthma. At the
present study the histopathology of fatal paediatric and adolescent asthma is
evaluated. METHODS: Post-mortem lung autopsies from 12 fatal asthma cases and 8
non-asthmatic control subjects were examined. Thickness of reticular basement
membrane (RBM) and percentage of airway smooth muscle (ASM%) mass area were
measured and inflammatory cells were counted. Patient records were reviewed for
clinical history. RESULTS: The age range of the cases was from 0.9 to 19.5 years,
eight were males and five had received inhaled corticosteroids. Thickened RBM was
detected in majority of the cases without any correlation to treatment delay, age
at onset of symptoms or diagnosis. In the large airways ASM was clearly increased
in one third of the cases whereas the median ASM% did not differ from that in
healthy controls (14.0% vs. 14.0%). In small airways no increase of ASM was
found, instead mucous plugs were seen in fatal asthma. The number of eosinophils,
plasmacytoid dendritic cells, macrophages, and B-cells were significantly
increased in fatal asthma cases compared with controls and the two latter
correlated with the length of the fatal exacerbation. CONCLUSIONS: The findings
highlight the strong presence of eosinophils and mucous plugs even in small
airways in children and adolescents with fatal asthma. Thickened RBM was obvious
in majority of the patients. Contrary to our hypothesis, increased ASM% was
detected in only one third of the patients.
PMID- 28511698
TI - Using a mobile health application to reduce alcohol consumption: a mixed-methods
evaluation of the drinkaware track & calculate units application.
AB - BACKGROUND: Smartphone applications ("apps") offer promise as tools to help
people monitor and reduce their alcohol consumption. To date, few evaluations of
alcohol reduction apps exist, with even fewer considering apps already available
to the public. The aim of this study was to evaluate an existing publically
available app, designed by Drinkaware, a UK-based alcohol awareness charity.
METHODS: We adopted a mixed-methods design, analysing routinely collected app
usage data to explore user characteristics and patterns of usage. Following this,
in-depth interviews were conducted with a sub-sample of app users to examine
perceptions of acceptability, usability and perceived effectiveness, as well as
to provide recommendations on how to improve the app. RESULTS: One hundred
nineteen thousand seven hundred thirteen people downloaded and entered data into
the app over a 13-month period. High attrition was observed after 1 week. Users
who engaged with the app tended to be "high risk" drinkers and to report being
motivated "to reduce drinking" at the point of first download. In those who
consistently engaged with the app over time, self-reported alcohol consumption
levels reduced, with most change occurring in the first week of usage. Our
qualitative findings indicate satisfaction with the usability of the app, but
mixed feedback was given regarding individual features. Users expressed
conflicting views concerning the type of feedback and notifications that the app
currently provides. A common preference was expressed for more personalised
content. CONCLUSIONS: The Drinkaware app is a useful tool to support behaviour
change in individuals who are already motivated and committed to reducing their
alcohol consumption. The Drinkaware app would benefit from greater
personalisation and tailoring to promote longer term use. This evaluation
provides insight into the usability and acceptability of various app features and
contains a number of recommendations for improving user satisfaction and the
potential effectiveness of apps designed to encourage reductions in alcohol
consumption.
PMID- 28511699
TI - Does intraoperative closed-suction drainage influence the rate of pancreatic
fistula after pancreaticoduodenectomy?
AB - BACKGROUND: Although drainage of pancreatic anastomoses after
pancreaticoduodenectomy (PD) is still debated, it remains recommended, especially
in patients with a high risk of post-operative pancreatic fistula (POPF).
Modalities of drainage of pancreatic anastomoses, especially the use of passive
(PAD) or closed-suction (CSD) drains, and their impact on surgical outcomes, have
been poorly studied. The aim was to compare CSD versus PAD on surgical outcomes
after PD. METHODS: Retrospective analysis of 197 consecutive patients who
underwent a standardized PD at two tertiary centers between March 2012 and April
2015. Patients with PAD (n = 132) or CSD (n = 65) were compared. RESULTS: There
was no significant difference in terms of 30-day overall and severe post
operative morbidity, post-operative hemorrhage, post-operative intra-abdominal
fluid collections, 90-day post-operative mortality and mean length of hospital
stay. The rate of POPF was significantly increased in the CSD group (47.7% vs.
32.6%; p = 0.04). CSD was associated with an increase of grade A POPF (21.5% vs.
8.3%; p = 0.03), while clinically relevant POPF were not impacted. In patients
with grade A POPF, the rate of undrained intra-abdominal fluid collections was
increased in the PAD group (46.1% vs. 21.4%; p = 0.18). After multivariate
analysis, CSD was an independent factor associated with an increased rate of POPF
(OR = 2.43; p = 0.012). CONCLUSIONS: There was no strongly relevant difference in
terms of surgical outcomes between PAD or CSD of pancreatic anastomoses after PD,
but CSD may help to decrease the rate of undrained post-operative intra-abdominal
collections in some patients. Further randomized, multi-institutional studies are
needed.
PMID- 28511700
TI - A new, easy-to-make pectin-honey hydrogel enhances wound healing in rats.
AB - BACKGROUND: Honey, alone or in combination, has been used for wound healing since
ancient times and has reemerged as a topic of interest in the last decade. Pectin
has recently been investigated for its use in various biomedical applications
such as drug delivery, skin protection, and scaffolding for cells. The aim of the
present study was to develop and evaluate a pectin-honey hydrogel (PHH) as a
wound healing membrane and to compare this dressing to liquid honey. METHODS:
Thirty-six adult male Sprague-Dawley rats were anesthetized and a 2 * 2 cm
excisional wound was created on the dorsum. Animals were randomly assigned to
four groups (PHH, LH, Pec, and C): in the PHH group, the pectin-honey hydrogel
was applied under a bandage on the wound; in the LH group, liquid Manuka honey
was applied; in the Pec group, pectin hydrogel was applied (Pec); and in the C
group, only bandage was applied to the wound. Images of the wound were taken at
defined time points, and the wound area reduction rate was calculated and
compared between groups. RESULTS: The wound area reduction rate was faster in the
PHH, LH, and Pec groups compared to the control group and was significantly
faster in the PHH group. Surprisingly, the Pec group exhibited faster wound
healing than the LH group, but this effect was not statistically significant.
CONCLUSION: This is the first study using pectin in combination with honey to
produce biomedical hydrogels for wound treatment. The results indicate that the
use of PHH is effective for promoting and accelerating wound healing.
PMID- 28511702
TI - What is the evidence for the management of patients along the pathway from the
emergency department to acute admission to reduce unplanned attendance and
admission? An evidence synthesis.
AB - BACKGROUND: Globally, the rate of emergency hospital admissions is increasing.
However, little evidence exists to inform the development of interventions to
reduce unplanned Emergency Department (ED) attendances and hospital admissions.
The objective of this evidence synthesis was to review the evidence for
interventions, conducted during the patient's journey through the ED or acute
care setting, to manage people with an exacerbation of a medical condition to
reduce unplanned emergency hospital attendance and admissions. METHODS: A rapid
evidence synthesis, using a systematic literature search, was undertaken in the
electronic data bases of MEDLINE, EMBASE, CINAHL, the Cochrane Library and Web of
Science, for the years 2000-2014. Evidence included in this review was restricted
to Randomised Controlled Trials (RCTs) and observational studies (with a control
arm) reported in peer-reviewed journals. Studies evaluating interventions for
patients with an acute exacerbation of a medical condition in the ED or acute
care setting which reported at least one outcome related to ED attendance or
unplanned admission were included. RESULTS: Thirty papers met our inclusion
criteria: 19 intervention studies (14 RCTs) and 11 controlled observational
studies. Sixteen studies were set in the ED and 14 were conducted in an acute
setting. Two studies (one RCT), set in the ED were effective in reducing ED
attendance and hospital admission. Both of these interventions were initiated in
the ED and included a post-discharge community component. Paradoxically 3 ED
initiated interventions showed an increase in ED re-attendance. Six studies (1
RCT) set in acute care settings were effective in reducing: hospital admission,
ED re-attendance or re-admission (two in an observation ward, one in an ED
assessment unit and three in which the intervention was conducted within 72 h of
admission). CONCLUSIONS: There is no clear evidence that specific interventions
along the patient journey from ED arrival to 72 h after admission benefit ED re
attendance or readmission. Interventions targeted at high-risk patients,
particularly the elderly, may reduce ED utilization and warrant future research.
Some interventions showing effectiveness in reducing unplanned ED attendances and
admissions are delivered by appropriately trained personnel in an environment
that allows sufficient time to assess and manage patients.
PMID- 28511701
TI - Easi-CRISPR: a robust method for one-step generation of mice carrying conditional
and insertion alleles using long ssDNA donors and CRISPR ribonucleoproteins.
AB - BACKGROUND: Conditional knockout mice and transgenic mice expressing
recombinases, reporters, and inducible transcriptional activators are key for
many genetic studies and comprise over 90% of mouse models created. Conditional
knockout mice are generated using labor-intensive methods of homologous
recombination in embryonic stem cells and are available for only ~25% of all
mouse genes. Transgenic mice generated by random genomic insertion approaches
pose problems of unreliable expression, and thus there is a need for targeted
insertion models. Although CRISPR-based strategies were reported to create
conditional and targeted-insertion alleles via one-step delivery of targeting
components directly to zygotes, these strategies are quite inefficient. RESULTS:
Here we describe Easi-CRISPR (Efficient additions with ssDNA inserts-CRISPR), a
targeting strategy in which long single-stranded DNA donors are injected with pre
assembled crRNA + tracrRNA + Cas9 ribonucleoprotein (ctRNP) complexes into mouse
zygotes. We show for over a dozen loci that Easi-CRISPR generates correctly
targeted conditional and insertion alleles in 8.5-100% of the resulting live
offspring. CONCLUSIONS: Easi-CRISPR solves the major problem of animal genome
engineering, namely the inefficiency of targeted DNA cassette insertion. The
approach is robust, succeeding for all tested loci. It is versatile, generating
both conditional and targeted insertion alleles. Finally, it is highly efficient,
as treating an average of only 50 zygotes is sufficient to produce a correctly
targeted allele in up to 100% of live offspring. Thus, Easi-CRISPR offers a
comprehensive means of building large-scale Cre-LoxP animal resources.
PMID- 28511703
TI - Mindfulness-based stress reduction for people with multiple sclerosis - a
feasibility randomised controlled trial.
AB - BACKGROUND: Multiple sclerosis (MS) is a stressful condition. Mental health
comorbidity is common. Stress can increase the risk of depression, reduce quality
of life (QOL), and possibly exacerbate disease activity in MS. Mindfulness-Based
Stress Reduction (MBSR) may help, but has been little studied in MS, particularly
among more disabled individuals. METHODS: The objective of this study was to test
the feasibility and likely effectiveness of a standard MBSR course for people
with MS. Participant eligibility included: age > 18, any type of MS, an Expanded
Disability Status Scale (EDSS) = 7.0. Participants received either MBSR or wait
list control. Outcome measures were collected at baseline, post-intervention, and
three-months later. Primary outcomes were perceived stress and QOL. Secondary
outcomes were common MS symptoms, mindfulness, and self-compassion. RESULTS:
Fifty participants were recruited and randomised (25 per group). Trial retention
and outcome measure completion rates were 90% at post-intervention, and 88% at 3
months. Sixty percent of participants completed the course. Immediately post
MBSR, perceived stress improved with a large effect size (ES 0.93; p < 0.01),
compared to very small beneficial effects on QOL (ES 0.17; p = 0.48). Depression
(ES 1.35; p < 0.05), positive affect (ES 0.87; p = 0.13), anxiety (ES 0.85; p =
0.05), and self-compassion (ES 0.80; p < 0.01) also improved with large effect
sizes. At three-months post-MBSR (study endpoint) improvements in perceived
stress were diminished to a small effect size (ES 0.26; p = 0.39), were
negligible for QOL (ES 0.08; p = 0.71), but were large for mindfulness (ES 1.13;
p < 0.001), positive affect (ES 0.90; p = 0.54), self-compassion (ES 0.83; p <
0.05), anxiety (ES 0.82; p = 0.15), and prospective memory (ES 0.81; p < 0.05).
CONCLUSIONS: Recruitment, retention, and data collection demonstrate that a RCT
of MBSR is feasible for people with MS. Trends towards improved outcomes suggest
that a larger definitive RCT may be warranted. However, optimisation changes may
be required to render more stable the beneficial treatment effects on stress and
depression. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02136485 ; trial
registered 1st May 2014.
PMID- 28511704
TI - The use of kDNA minicircle subclass relative abundance to differentiate between
Leishmania (L.) infantum and Leishmania (L.) amazonensis.
AB - BACKGROUND: Leishmaniasis is a neglected disease caused by many Leishmania
species, belonging to subgenera Leishmania (Leishmania) and Leishmania (Viannia).
Several qPCR-based molecular diagnostic approaches have been reported for
detection and quantification of Leishmania species. Many of these approaches use
the kinetoplast DNA (kDNA) minicircles as the target sequence. These assays had
potential cross-species amplification, due to sequence similarity between
Leishmania species. Previous works demonstrated discrimination between L.
(Leishmania) and L. (Viannia) by SYBR green-based qPCR assays designed on kDNA,
followed by melting or high-resolution melt (HRM) analysis. Importantly, these
approaches cannot fully distinguish L. (L.) infantum from L. (L.) amazonensis,
which can coexist in the same geographical area. METHODS: DNA from 18
strains/isolates of L. (L.) infantum, L. (L.) amazonensis, L. (V.) braziliensis,
L. (V.) panamensis, L. (V.) guyanensis, and 62 clinical samples from L. (L.)
infantum-infected dogs were amplified by a previously developed qPCR (qPCR-ML)
and subjected to HRM analysis; selected PCR products were sequenced using an ABI
PRISM 310 Genetic Analyzer. Based on the obtained sequences, a new SYBR-green
qPCR assay (qPCR-ama) intended to amplify a minicircle subclass more abundant in
L. (L.) amazonensis was designed. RESULTS: The qPCR-ML followed by HRM analysis
did not allow discrimination between L. (L.) amazonensis and L. (L.) infantum in
53.4% of cases. Hence, the novel SYBR green-based qPCR (qPCR-ama) has been
tested. This assay achieved a detection limit of 0.1 pg of parasite DNA in
samples spiked with host DNA and did not show cross amplification with
Trypanosoma cruzi or host DNA. Although the qPCR-ama also amplified L. (L.)
infantum strains, the Cq values were dramatically increased compared to qPCR-ML.
Therefore, the combined analysis of Cq values from qPCR-ML and qPCR-ama allowed
to distinguish L. (L.) infantum and L. (L.) amazonensis in 100% of tested
samples. CONCLUSIONS: A new and affordable SYBR-green qPCR-based approach to
distinguish between L. (L.) infantum and L. (L.) amazonensis was developed
exploiting the major abundance of a minicircle sequence rather than targeting a
hypothetical species-specific sequence. The fast and accurate discrimination
between these species can be useful to provide adequate prognosis and treatment.
PMID- 28511705
TI - PD-L1 expressing circulating tumour cells in head and neck cancers.
AB - BACKGROUND: Blockade of the PD-1/PD-L1 immune checkpoint pathway is emerging as a
promising immunotherapeutic approach for the management and treatment of head and
neck cancer patients who do not respond to 1st/2nd line therapy. However, as
checkpoint inhibitors are cost intensive, identifying patients who would most
likely benefit from anti PD-L1 therapy is required. Developing a non-invasive
technique would be of major benefit to the patient and to the health care system.
CASE PRESENTATION: We report the case of a 56 year old man affected by a
supraglottic squamous cell carcinoma (SCC). A CT scan showed a 20 mm right
jugulodigastric node and suspicious lung lesions. The lung lesion was biopsied
and confirmed to be consistent with SCC. The patient was offered palliative
chemotherapy. At the time of presentation, a blood sample was taken for
circulating tumour cell (CTC) analysis. The dissemination of cancer was confirmed
by the detection of CTCs in the peripheral blood of the patient, measured by the
CellSearch System (Janssen Diagnostics). Using marker-independent, low-shear
spiral microfluidic technology combined with immunocytochemistry, CTC clusters
were found in this patient at the same time point, expressing PD-L1. CONCLUSION:
This report highlights the potential use of CTCs to identify patients which might
respond to anti PD-L1 therapy.
PMID- 28511707
TI - Rapid deployment valve system shortens operative times for aortic valve
replacement through right anterior minithoracotomy.
AB - BACKGROUND: There is growing evidence from the literature that right anterior
minithoracotomy aortic valve replacement (RAT-AVR) improves clinical outcome.
However, increased cross clamp time is the strongest argument for surgeons not
performing RAT-AVR. Rapid deployment aortic valve systems have the potential to
decrease cross-clamp time and ease this procedure. We assessed clinical outcome
of rapid deployment and conventional valves through RAT. METHODS: Sixty-eight
patients (mean age 76 +/- 6 years, 32% females) underwent RAT-AVR between 9/2013
and 7/2015. According to the valve type implanted the patients were divided into
two groups. In 43 patients (R-group; mean age 74.1 +/- 6.6 years) a rapid
deployment valve system (Edwards Intuity, Edwards Lifesciences Corp; Irvine,
Calif) and in 25 patients (C-group; mean age 74.2 +/- 6.6 years) a conventional
stented biological aortic valve was implanted. RESULTS: Aortic cross-clamp (42.1
+/- 12 min vs. 68.3 +/- 20.3 min; p < 0.001) and bypass time (80.4 +/- 39.3 min
vs. 106.6 +/- 23.2 min; p = 0.001) were shorter in the rapid deployment group (R
group). We observed no differences in clinical outcome. Postoperative gradients
(R-group: max gradient, 14.3 +/- 8 mmHg vs. 15.5 +/- 5 mmHg (C-group), mean
gradient, 9.2 +/- 1.7 mmHg (R-group) vs. 9.1 +/- 2.3 mmHg (C-group) revealed no
differences. However, larger prostheses were implanted in C-group (25 mm; IQR 23
27 mm vs. 23 mm; IQR 21-25; p = 0.009). CONCLUSIONS: Our data suggest that the
rapid deployment aortic valve system reduced cross clamp and bypass time in
patients undergoing RAT-AVR with similar hemodynamics as with larger size stented
prosthesis. However, larger studies and long-term follow-up are mandatory to
confirm our findings.
PMID- 28511708
TI - Enzyme-mediated formulation of stable elliptical silver nanoparticles tested
against clinical pathogens and MDR bacteria and development of antimicrobial
surgical thread.
AB - BACKGROUND: Silver nanoparticles (AgNPs) are believed to be emerging tool against
various infectious diseases including multi-drug resistant (MDR) bacteria. In the
present study, in vitro synthesis of AgNPs was optimized using 1:50 ratio of
macerozyme (25 MUg/MUl) and 1 mM AgNO3 incubated at 80 degrees C for 8 h. AgNPs
were characterized by UV-Visible spectroscopy, dynamic light scattering (DLS),
scanning electron microscopy, energy-dispersive X-ray spectroscopy, transmission
electron microscopy (TEM) and X-ray diffraction (XRD). RESULTS: Characterization
studies suggest the synthesis of elliptical, stable and crystalline AgNPs with an
average size of 38.26 +/- 0.4 nm calculated using TEM. The XRD pattern revealed
the face-centered-cubic (fcc) form of metallic silver. Good shape integrity and
dispersion of AgNPs after 1 year of incubation confirmed their stability. AgNPs
were exibited the antimicrobial property against ten pathogenic bacteria, three
molds and one yeast. The AgNPs also revealed remarkable antimicrobial activity
against three MDR strains i.e. Extended spectrum beta-lactamase positive
Escherichia coli, Staphylococcus aureus (MRSA) and Teicoplanin resistant
Streptococcus Pneumoniae. The AgNPs coated surgical threads (suture) were
revealed the remarkble antibacterial activity against three MDR strains. This is
the first report to synthesize antimicrobial elliptical AgNPs using enzymes.
CONCLUSION: The results suggest the possibilities to develop the nanoparticles
coated antimicrobial medical fabric to combat against MDR infection.
PMID- 28511709
TI - Incorporation of high-dose 131I-metaiodobenzylguanidine treatment into tandem
high-dose chemotherapy and autologous stem cell transplantation for high-risk
neuroblastoma: results of the SMC NB-2009 study.
AB - BACKGROUND: In our previous SMC NB-2004 study of patients with high-risk
neuroblastomas, which incorporated total-body irradiation (TBI) with second high
dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT), the
survival rate was encouraging; however, short- and long-term toxicities were
significant. In the present SMC NB-2009 study, only TBI was replaced with 131I
meta-iodobenzylguanidine (MIBG) treatment in order to reduce toxicities. METHODS:
From January 2009 to December 2013, 54 consecutive patients were assigned to
receive tandem HDCT/auto-SCT after nine cycles of induction chemotherapy. The CEC
(carboplatin + etoposide + cyclophosphamide) regimen and the TM (thiotepa +
melphalan) regimen with (for metastatic MIBG avid tumors) or without (for
localized or MIBG non-avid tumors) 131I-MIBG treatment (18 or 12 mCi/kg) were
used for tandem HDCT/auto-SCT. Local radiotherapy, differentiation therapy with
13-cis-retinoic acid, and immunotherapy with interleukin-2 were administered
after tandem HDCT/auto-SCT. RESULTS: Fifty-two patients underwent the first
HDCT/auto-SCT and 47 patients completed tandem HDCT/auto-SCT. There was no
significant immediate toxicity during the 131I-MIBG infusion. Acute toxicities
during the tandem HDCT/auto-SCT were less severe in the NB-2009 study than in the
NB-2004 study. Late effects such as growth hormone deficiency, cataracts, and
glomerulopathy evaluated at 3 years after the second HDCT/auto-SCT were also less
significant in the NB-2009 study than in NB-2004 study. There was no difference
in the 5-year event-free survival (EFS) between the two studies (67.5 +/- 6.7%
versus 58.3 +/- 6.9%, P = 0.340). CONCLUSIONS: Incorporation of high-dose 131I
MIBG treatment into tandem HDCT/auto-SCT could reduce short- and long-term
toxicities associated with TBI, without jeopardizing the survival rate. TRIAL
REGISTRATION: ClinicalTrials.gov NCT03061656.
PMID- 28511710
TI - Association between leisure time physical activity preference and behavior:
evidence from the China Health & Nutrition Survey, 2004-2011.
AB - BACKGROUND: Previous studies have suggested that food preference is a good
indicator of actual food intake and that sedentary activity preference is a
significant predictor of lower physical activity level. But no studies have
examined the direct relationship between leisure time physical activity (LTPA)
preferences and actual LTPA behavior, especially studies using longitudinal data.
This study seeks to determine the association between these two variables, and to
assess whether the association differs between urban and rural areas in China.
METHODS: A total of 2427 Chinese adults were included in the analysis. Spearman
correlation coefficients were used to test the association between leisure time
physical activity preference and behavior, followed by multiple logistic
regressions to further examine the association after adjusting for possible
confounding variables. Urban-rural differences in the association were
investigated through stratified analysis. RESULTS: In the sample, 63.0% were from
urban areas, 47.4% were men, and the mean age was 40. Adjusted estimates based on
logistic regression show that LTPA preference was a significant predictor of
actual LTPA behavior (OR = 1.05, 95% CI = 1.01-1.09). The correlation was found
to be significant among urban residents (OR = 1.06, 95% CI = 1.01-1.10), but not
in rural residents. CONCLUSIONS: The study illustrates the predictive value of
LTPA preference for actual LTPA behavior. Changing LTPA preference to promote
LTPA may be helpful in preventing and controlling chronic disease in China.
PMID- 28511706
TI - Analgesic antipyretic use among young children in the TEDDY study: no association
with islet autoimmunity.
AB - BACKGROUND: The use of analgesic antipyretics (ANAP) in children have long been a
matter of controversy. Data on their practical use on an individual level has,
however, been scarce. There are indications of possible effects on glucose
homeostasis and immune function related to the use of ANAP. The aim of this study
was to analyze patterns of analgesic antipyretic use across the clinical centers
of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective
cohort study and test if ANAP use was a risk factor for islet autoimmunity.
METHODS: Data were collected for 8542 children in the first 2.5 years of life.
Incidence was analyzed using logistic regression with country and first child
status as independent variables. Holm's procedure was used to adjust for
multiplicity of intercountry comparisons. Time to autoantibody seroconversion was
analyzed using a Cox proportional hazards model with cumulative analgesic use as
primary time dependent covariate of interest. For each categorization, a
generalized estimating equation (GEE) approach was used. RESULTS: Higher
prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared
to Finland (78.1%) and Germany (80.2%). First-born children were more commonly
given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non
Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p =
0.002). Acetaminophen and NSAID use in the absence of fever and infection was
more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland
and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not
predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99
1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever
weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95%
CI 1.01-1.09; p = 0.024). CONCLUSIONS: ANAP use in young children is not a risk
factor for seroconversion by age 6 years. Use of ANAP is widespread in young
children, and significantly higher in the U.S. compared to other study sites,
where use is common also in absence of fever and infection.
PMID- 28511712
TI - What we learned from extended culture of 'rejected' day-3 cleavage stage embryos:
a prospective cohort study.
AB - BACKGROUND: To test whether poor quality day-3 embryos can undergo successful
blastulation and implantation. METHODS: A prospective cohort study was conducted.
Whether or not a good quality embryo was transferred on day-3, poor quality
(rejected) embryos were further cultured and followed. The clinical outcome of
each embryo was assessed. RESULTS: A total of 694 rejected embryos (from 205
patients) were included, with a blastulation rate of 21.2% (147 embryos) compared
to 64.2% general blastulation rate reported by our laboratory (P < 0.01). In a
multivariate logistic regression model, only their grade on day-3 significantly
affected blastulation (P = 0.01). A total of 97 embryos attained eligibility for
fresh transfer or cryopreservation, only 6 of which resulted from a day-3 embryo
scored < 2. Of these, 52 were transferred, resulting in 21 pregnancies (16
clinical and 5 chemical). In summary, 694 cultured embryos yielded 16 clinical
pregnancies; a 2.3% clinical pregnancy rate. CONCLUSIONS: Low score day-3 embryos
can result in successful blastulation and clinical pregnancies. However, the
normal blastulation rate is poor.
PMID- 28511711
TI - SGLT2 inhibitors: a novel choice for the combination therapy in diabetic kidney
disease.
AB - Diabetic kidney disease (DKD) is the most common cause of end stage renal
disease. The comprehensive management of DKD depends on combined target-therapies
for hyperglycemia, hypertension, albuminuria, and hyperlipaemia, etc. Sodium
glucose co-transporter 2 (SGLT2) inhibitors, the most recently developed oral
hypoglycemic agents acted on renal proximal tubules, suppress glucose
reabsorption and increase urinary glucose excretion. Besides improvements in
glycemic control, they presented excellent performances in direct renoprotective
effects and the cardiovascular (CV) safety by decreasing albuminuria and the
independent CV risk factors such as body weight and blood pressure, etc.
Simultaneous use of SGLT-2 inhibitors and renin-angiotensin-aldosterone system
(RAAS) blockers are novel strategies to slow the progression of DKD via reducing
inflammatory and fibrotic markers induced by hyperglycaemia more than either drug
alone. The available population and animal based studies have described SGLT2
inhibitors plus RAAS blockers. The present review was to systematically review
the potential renal benefits of SGLT2 inhibitors combined with dipeptidyl
peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists,
mineralocorticoid receptor antagonists, and especially the angiotensin-converting
enzyme inhibitors/angiotensin receptor blockers.
PMID- 28511714
TI - Assessing equity in the distribution of high-technology medical equipment in
Guangxi: evidence from an ethnic minority region in Southern China.
AB - BACKGROUND: High-technology medical equipment (HTME) are important health
resources. However, there is unequal distribution of these equipment in favor of
metropolis and well equipped health facilities. This study sought to examine the
equity gaps in the distribution of HTME in Guangxi. The results of this study
could shed light on the future HTME allocation in Guangxi Zhuang Autonomous
Region. METHODS: Data related to HTME was sourced from a general investigation of
all the hospitals of Guangxi. Concentration index was used to assess the equity
status of HTME in Guangxi. RESULTS: Over all, the total amount of HTME in Guangxi
had been increasing from 2011 to 2015, and the per million population HTME of
five kinds were all increased at the same time. Meanwhile, the concentration
indices ranged between 0.1020 and 0.4617. The five medical equipment were all
concentrated among the rich. CONCLUSIONS: The possession of SPECT per million
population in Guangxi is lower than the national average level while it is
superior to the national average level for CT, MRI, DSA and LA. The equity status
in the distribution of the five medical equipment has deteriorated since 2011. In
2015, the equity status of CT was the best, while the equity status of MRI was
the worst. Meanwhile, 45.1% of HTME were concentrated in Nanning, Guilin, and
Liuzhou.
PMID- 28511713
TI - Artemisinin-based combination therapy in pregnant women in Zambia: efficacy,
safety and risk of recurrent malaria.
AB - BACKGROUND: In Zambia, malaria is one of the leading causes of morbidity and
mortality, especially among under five children and pregnant women. For the
latter, the World Health Organization recommends the use of artemisinin-based
combination therapy (ACT) in the second and third trimester of pregnancy. In a
context of limited information on ACT, the safety and efficacy of three
combinations, namely artemether-lumefantrine (AL), mefloquine-artesunate (MQAS)
and dihydroartemisinin-piperaquine (DHAPQ) were assessed in pregnant women with
malaria. METHODS: The trial was carried out between July 2010 and August 2013 in
Nchelenge district, Luapula Province, an area of high transmission, as part of a
multi-centre trial. Women in the second or third trimester of pregnancy and with
malaria were recruited and randomized to one of the three study arms. Women were
actively followed up for 63 days, and then at delivery and 1 year post-delivery.
RESULTS: Nine hundred pregnant women were included, 300 per arm. PCR-adjusted
treatment failure was 4.7% (12/258) (95% CI 2.7-8.0) for AL, 1.3% (3/235) (95% CI
0.4-3.7) for MQAS and 0.8% (2/236) (95% CI 0.2-3.0) for DHAPQ, with significant
risk difference between AL and DHAPQ (p = 0.01) and between AL and MQAS (p =
0.03) treatments. Re-infections during follow up were more frequent in the AL
(HR: 4.71; 95% CI 3.10-7.2; p < 0.01) and MQAS (HR: 1.59; 95% CI 1.02-2.46; p =
0.04) arms compared to the DHAPQ arm. PCR-adjusted treatment failure was
significantly associated with women under 20 years [Hazard Ratio (HR) 5.35 (95%
CI 1.07-26.73; p = 0.04)] and higher malaria parasite density [3.23 (95% CI 1.03
10.10; p = 0.04)], and still women under 20 years [1.78, (95% CI 1.26-2.52; p <
0.01)] had a significantly higher risk of re-infection. The three treatments were
generally well tolerated. Dizziness, nausea, vomiting, headache and asthenia as
adverse events (AEs) were more common in MQAS than in AL or DHAPQ (p < 0.001).
Birth outcomes were not significantly different between treatment arms.
CONCLUSION: As new infections can be prevented by a long acting partner drug to
the artemisinins, DHAPQ should be preferred in places as Nchelenge district where
transmission is intense while in areas of low transmission intensity AL or MQAS
may be used.
PMID- 28511716
TI - Retraction Note to: Inotropic therapy for cardiac low output syndrome: comparison
of hemodynamic effects of dopamine/dobutamine versus dopamine/dopexamine.
PMID- 28511717
TI - Pancreatic beta-cell regeneration: advances in understanding the genes and
signaling pathways involved.
AB - Recent advances in beta-cell regeneration in vivo are providing insights into the
mechanisms involved in the conversion of distinct pancreatic cell lineages into
beta cells. These mechanisms mostly involve reactivation of the gene encoding the
pancreatic endocrine cell-specifying transcription factor neurogenin-3.
PMID- 28511715
TI - Erratum to: Elaboration of a nomogram to predict nonsentinel node status in
breast cancer patients with positive sentinel node, intraoperatively assessed
with one step nucleic amplification: Retrospective and validation phase.
PMID- 28511718
TI - Simultaneous development of Kawasaki disease following acute human adenovirus
infection in monozygotic twins: A case report.
AB - BACKGROUND: The etiology of Kawasaki disease (KD) remains unknown. However, many
studies have suggested that specific genetic factors and/or some infectious
agents underlie the onset of KD. Previous studies have suggested that human
adenovirus (HAdV) is one of the triggering pathogens of KD. Here, we report
monozygotic twin boys who sequentially developed KD in conjunction with acute
HAdV type 3 (HAdV-3) infection. CASE PRESENTATION: The patients were four-year
old monozygotic twin boys. The elder brother developed a high fever and was
diagnosed with HAdV infection with an immunochromatographic kit for HAdV (IC
kit). He was transferred to our institute after persistent fever for 7 days. On
admission, he already fulfilled all the diagnostic criteria for KD. His
laboratory data were as follows: WBC, 9700/MUl; CRP, 2.42 mg/dl; IFN-gamma, 99.8
pg/ml; and TNF-alpha, 10.9 pg/ml. He received intravenous immunoglobulin (IVIG)
and aspirin and responded well, with no coronary artery abnormalities. The
younger brother, who was also IC-kit-positive, was hospitalized on the same day
as his elder brother after persistent fever for 3 days. His data on admission
were as follows: WBC, 12,600/MUl; CRP, 5.54 mg/dl; IFN-gamma, 105.0 pg/ml; and
TNF-alpha, 33.6 pg/ml. Although he developed all of the typical KD symptoms by
day 4, his fever subsided spontaneously on day 6 without IVIG or aspirin.
However, he developed a dilation of the coronary artery in the region of the left
circumflex artery bifurcation on day 10. His coronary artery dilation had
resolved 3 months after onset. HAdV-3 DNA was detected with PCR in stool samples
from both patients, and HAdV3 was isolated from the younger brother's stool
sample. Serum neutralizing antibodies to AdV3 were also significantly elevated in
both patients, suggesting seroconversion. CONCLUSIONS: There have been few
reports of the simultaneous development of KD in monozygotic twins. Notably, both
twins had an acute HAdV-3 infection immediately before they developed KD. These
cases strongly suggest that KD was triggered by HAdV-3 infection, and they
indicate that specific immune responses to some pathogens (such as HAdV-3),
arising from genetic susceptibility, play a critical role in the pathogenesis of
KD.
PMID- 28511720
TI - Identifying models of delivery, care domains and quality indicators relevant to
palliative day services: a scoping review protocol.
AB - BACKGROUND: With an ageing population and increasing numbers of people with life
limiting illness, there is a growing demand for palliative day services. There is
a need to measure and demonstrate the quality of these services, but there is
currently little agreement on which aspects of care should be used to do this.
The aim of the scoping review will be to map the extent, range and nature of the
evidence around models of delivery, care domains and existing quality indicators
used to evaluate palliative day services. METHODS: Electronic databases (MEDLINE,
EMBASE, CINAHL, PsycINFO, Cochrane Central Register of Controlled Trials) will be
searched for evidence using consensus development methods; randomised or quasi
randomised controlled trials; mixed methods; and prospective, longitudinal or
retrospective case-control studies to develop or test quality indicators for
evaluating palliative care within non-residential settings, including day
hospices and community or primary care settings. At least two researchers will
independently conduct all searches, study selection and data abstraction
procedures. Meta-analyses and statistical methods of synthesis are not planned as
part of the review. Results will be reported using numerical counts, including
number of indicators in each care domain and by using qualitative approach to
describe important indicator characteristics. A conceptual model will also be
developed to summarise the impact of different aspects of quality in a palliative
day service context. Methodological quality relating to indicator development
will be assessed using the Appraisal of Indicators through Research and
Evaluation (AIRE) tool. Overall strength of evidence will be assessed using the
Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)
system. Final decisions on quality assessment will be made via consensus between
review authors. DISCUSSION: Identifying, developing and implementing evidence
based quality indicators is critical to the evaluation and continued improvement
of palliative care. Review findings will be used to support clinicians and
policymakers make decisions on which quality indicators are most appropriate for
evaluating day services at the patient and service level, and to identify areas
for further research.
PMID- 28511719
TI - Interleukin-10-producing LAG3+ regulatory T cells are associated with disease
activity and abatacept treatment in rheumatoid arthritis.
AB - BACKGROUND: Regulatory T cells (Tregs) play a role in the suppression of
inflammation in autoimmune diseases, and lymphocyte activation gene 3 (LAG3) was
reported as a marker of interleukin (IL)-10-producing Tregs. We aimed to clarify
the function of human IL-10-producing CD4+CD25-LAG3+ T cells (LAG3+ Tregs) and
their association with rheumatoid arthritis (RA). METHODS: LAG3+ Tregs of human
peripheral blood mononuclear cells (PBMCs) were cultured with B cells and
follicular helper T cells to examine antibody suppression effects. The frequency
of LAG3+ Tregs was evaluated in peripheral blood samples from 101 healthy donors
and 85 patients with RA. In patients treated with abatacept, PBMC samples were
analyzed before and after treatment. Naive CD4+ T cells were sorted and cultured
in the presence of abatacept, followed by flow cytometric analysis and function
assays. RESULTS: LAG3+ Tregs produced high amounts of IL-10 and interferon-gamma,
and they suppressed B-cell antibody production more strongly than CD25+ Tregs.
Cell-to-cell contact was required for the suppressive function of LAG3+ Tregs.
The frequency of LAG3+ Tregs was lower in patients with RA, especially those with
higher Clinical Disease Activity Index scores. LAG3+ Tregs significantly
increased after 6 months of abatacept treatment, whereas CD25+ Tregs generally
decreased. Abatacept treatment in vitro conferred LAG3 and EGR2 expression on
naive CD4+ T cells, and abatacept-treated CD4+ T cells exhibited suppressive
activity. CONCLUSIONS: IL-10-producing LAG3+ Tregs are associated with the
immunopathology and therapeutic response in RA. LAG3+ Tregs may participate in a
mechanism for the anti-inflammatory and immune-modulating effects of targeted
therapy for costimulation.
PMID- 28511722
TI - Use of Rapid Ascertainment Process for Institutional Deaths (RAPID) to identify
pregnancy-related deaths in tertiary-care obstetric hospitals in three
departments in Haiti.
AB - BACKGROUND: Accurate assessment of maternal deaths is difficult in countries
lacking standardized data sources for their review. As a first step to
investigate suspected maternal deaths, WHO suggests surveillance of "pregnancy
related deaths", defined as deaths of women while pregnant or within 42 days of
termination of pregnancy, irrespective of cause. Rapid Ascertainment Process for
Institutional Deaths (RAPID), a surveillance tool, retrospectively identifies
pregnancy-related deaths occurring in health facilities that may be missed by
routine surveillance to assess gaps in reporting these deaths. METHODS: We used
RAPID to review pregnancy-related deaths in six tertiary obstetric care
facilities in three departments in Haiti. We reviewed registers and medical
dossiers of deaths among women of reproductive age occurring in 2014 and 2015
from all wards, along with any additional available dossiers of deaths not
appearing in registers, to capture pregnancy status, suspected cause of death,
and timing of death in relation to the pregnancy. We used capture-recapture
analyses to estimate the true number of in-hospital pregnancy-related deaths in
these facilities. RESULTS: Among 373 deaths of women of reproductive age, we
found 111 pregnancy-related deaths, 25.2% more than were reported through routine
surveillance, and 22.5% of which were misclassified as non-pregnancy-related.
Hemorrhage (27.0%) and hypertensive disorders (18.0%) were the most common
categories of suspected causes of death, and deaths after termination of
pregnancy were statistically significantly more common than deaths during
pregnancy or delivery. Data were missing at multiple levels: 210 deaths had an
undetermined pregnancy status, 48.7% of pregnancy-related deaths lacked specific
information about timing of death in relation to the pregnancy, and capture
recapture analyses in three hospitals suggested that approximately one-quarter of
pregnancy-related deaths were not captured by RAPID or routine surveillance.
CONCLUSIONS: Across six tertiary obstetric care facilities in Haiti, RAPID
identified unreported pregnancy-related deaths, and showed that missing data was
a widespread problem. RAPID is a useful tool to more completely identify facility
based pregnancy-related deaths, but its repeated use would require a concomitant
effort to systematically improve documentation of clinical findings in medical
records. Limitations of RAPID demonstrate the need to use it alongside other
tools to more accurately measure and address maternal mortality.
PMID- 28511723
TI - Feasibility and diagnostic performance of dual-tracer-guided sentinel lymph node
biopsy in cT1-2N0M0 gastric cancer: a systematic review and meta-analysis of
diagnostic studies.
AB - BACKGROUND: Dual-tracer-guided sentinel lymph node (SLN) biopsy may provide a
promising diagnostic tool to assess accurately the status of lymph node
metastasis in the surgical operation and assure the oncologic safety of the
function or stomach preserving surgery. The diagnostic performance of this
technology in recent studies varied. Thus, we conducted this meta-analysis.
METHODS: This systematic review and meta-analysis was registered at the PROSPERO.
Eligible studies were searched in the PubMed, EMBASE, Web of Knowledge, and
Cochrane Library databases. A random-effect model was used to pool the data.
Summary receiver operator characteristic curves, analysis for publication bias,
meta-regression, and subgroup analysis were also performed. RESULTS: The pooled
SLN identification rate and sensitivity were 0.97 and 0.89. 99mTc-human serum
albumin with indocyanine green (ICG), 99mTc-antimony sulfur colloid with ICG,
performing SLN biopsy >=15 min after dye injection, an SLN >=5, the basin
dissection, laparoscopic surgery, in studies conducted in Japan and studies
published after 2012, were associated with higher sensitivity. CT1 stage,
performing SLN biopsy >=15 min after dye injection, in studies conducted in Japan
and studies published after 2012, were related with a higher identification rate.
CONCLUSIONS: Dual tracer is promising in SLN biopsy in gastric cancer, and the
clinical application of SLN biopsy should be limited to the patients of cT1N0M0
gastric cancer. The combination of 99mTc-human serum albumin and ICG as well as
the combination of 99mTc-antimony sulfur colloid and ICG may be the optimal
tracer combination. However, it seems not justified to put this technique into
routine clinical application recently. Some factors that might enhance diagnostic
value are identified.
PMID- 28511724
TI - Production of a recombinant swollenin from Trichoderma harzianum in Escherichia
coli and its potential synergistic role in biomass degradation.
AB - BACKGROUND: Fungal swollenins (SWOs) constitute a class of accessory proteins
that are homologous to canonical plant expansins. Expansins and expansin-related
proteins are well known for acting in the deagglomeration of cellulose structure
by loosening macrofibrils. Consequently, SWOs can increase the accessibility and
efficiency of the other enzymes involved in the saccharification of cellulosic
substrates. Thus, SWOs are promising targets for improving the hydrolysis of
plant biomass and for use as an additive to enhance the efficiency of an enzyme
cocktail designed for the production of biofuels. RESULTS: Here, we report the
initial characterization of an SWO from Trichoderma harzianum (ThSwo) that was
successfully produced using Escherichia coli as a host. Initially, transcriptome
and secretome data were used to compare swo gene expression and the amount of
secreted ThSwo. The results from structural modeling and phylogenetic analysis of
the ThSwo protein showed that ThSwo does preserve some structural features of the
plant expansins and family-45 glycosyl hydrolase enzymes, but it evolutionarily
diverges from both of these protein classes. Recombinant ThSwo was purified at a
high yield and with high purity and showed secondary folding similar to that of a
native fungal SWO. Bioactivity assays revealed that the purified recombinant
ThSwo created a rough and amorphous surface on Avicel and displayed a high
synergistic effect with a commercial xylanase from T. viride, enhancing its
hydrolytic performance up to 147 +/- 7%. CONCLUSIONS: Many aspects of the
structure and mechanism of action of fungal SWOs remain unknown. In the present
study, we produced a recombinant, active SWO from T. harzianum using a
prokaryotic host and confirmed its potential synergistic role in biomass
degradation. Our work paves the way for further studies evaluating the structure
and function of this protein, especially regarding its use in biotechnology.
PMID- 28511725
TI - The performance of different classification criteria sets for spondyloarthritis
in the worldwide ASAS-COMOSPA study.
AB - BACKGROUND: In this study, we sought to compare the performance of
spondyloarthritis (SpA) classification criteria sets in an international SpA
cohort with patients included from five continents around the world. METHODS:
Data from the (ASAS) COMOrbidities in SPondyloArthritis (ASAS-COMOSPA) study were
used. ASAS-COMOSPA is a multinational, cross-sectional study with consecutive
patients diagnosed with SpA by rheumatologists worldwide. Patients were
classified according to the European Spondyloarthropathy Study Group (ESSG),
modified European Spondyloarthropathy Study Group (mESSG), Amor, modified Amor,
Assessment of SpondyloArthritis international Society (ASAS) axial
Spondyloarthritis (axSpA), ASAS peripheral spondyloarthritis (pSpA) and
ClASsification criteria for Psoriatic Arthritis (CASPAR) criteria. Overlap
between the classification criteria sets was assessed for patients with and
without back pain. Furthermore, patients fulfilling different arms of the ASAS
axSpA criteria (imaging arm, clinical arm, both arms) were compared on the
presence of SpA features. RESULTS: A total of 3942 patients (5 continents, 26
countries) were included. The mean age was 43.6 years, 65.0% were male, 56.2%
were human leucocyte antigen B27-positive and 64.4% had radiographic sacroiliitis
(based on modified New York criteria). Of the patients, 85.5% were classified by
the ASAS SpA criteria (87.7% ASAS axSpA, 12.3% ASAS pSpA). Fulfilment of the
Amor, ESSG and CASPAR criteria was present in 83.3%, 88.4% and 21.6% of patients,
respectively. Of the patients with back pain (n = 3227), most were classified by
all three of Amor, ESSG and ASAS axSpA criteria (71.4%). Patients fulfilling the
imaging arm and the clinical arm of the ASAS axSpA criteria had similar
presentations of SpA features. In patients without back pain, overlap between
classification criteria sets was seen, although to a lesser extent. CONCLUSIONS:
Most patients with a clinical diagnosis of axial SpA in the worldwide ASAS
COMOSPA study fulfil several classification criteria sets, and a substantial
overlap between different criteria sets is seen, which suggests a high level of
credibility of the criteria. Large inter-regional differences in the fulfilment
of classification criteria were not found. Patients fulfilling the clinical arm
were remarkably similar to patients fulfilling the imaging arm with respect to
the presence of most SpA features.
PMID- 28511721
TI - Socioeconomic status and dietary patterns in children from around the world:
different associations by levels of country human development?
AB - BACKGROUND: Although 'unhealthy' diet is a well-known risk factor for non
communicable diseases, its relationship with socio-economic status (SES) has not
been fully investigated. Moreover, the available research has largely been
conducted in countries at high levels of human development. This is the first
study to examine relationships among dietary patterns and SES of children from
countries spanning a wide range of human development. METHODS: This was a
multinational cross-sectional study among 9-11 year-old children (n = 6808) from
urban/peri-urban sites across 12 countries. Self-reported food frequency
questionnaires were used to determine the children's dietary patterns. Principal
Components Analysis was employed to create two component scores representing
'unhealthy' and 'healthy' dietary patterns. Multilevel models accounting for
clustering at the school and site level were used to examine the relationships
among dietary patterns and SES. RESULTS: The mean age of participants in this
study (53.7% girls) was 10.4 years. Largest proportions of total variance in
dietary patterns occurred at the individual, site, and school levels (individual,
school, site: 62.8%; 10.8%; 26.4% for unhealthy diet pattern (UDP) and 88.9%;
3.7%; 7.4%) for healthy diet pattern (HDP) respectively. There were significant
negative 'unhealthy' diet-SES gradients in 7 countries and positive 'healthy'
diet-SES gradients in 5. Within country diet-SES gradients did not significantly
differ by HDI. Compared to participants in the highest SES groups, unhealthy diet
pattern scores were significantly higher among those in the lowest within-country
SES groups in 8 countries: odds ratios for Australia (2.69; 95% CI: 1.33-5.42),
Canada (4.09; 95% CI: 2.02-8.27), Finland (2.82; 95% CI: 1.27-6.22), USA (4.31;
95% CI: 2.20-8.45), Portugal (2.09; 95% CI: 1.06-4.11), South Africa (2.77; 95%
CI: 1.22-6.28), India (1.88; 95% CI: 1.12-3.15) and Kenya (3.35; 95% CI: 1.91
5.87). CONCLUSIONS: This study provides evidence of diet-SES gradients across all
levels of human development and that lower within-country SES is strongly related
to unhealthy dietary patterns. Consistency in within-country diet-SES gradients
suggest that interventions and public health strategies aimed at improving
dietary patterns among children may be similarly employed globally. However,
future studies should seek to replicate these findings in more representative
samples extended to more rural representation.
PMID- 28511726
TI - Executive Functioning in Pedophilia and Child Sexual Offending.
AB - OBJECTIVES: Pedophilia (P) is a psychiatric disease associated with sexual
attraction toward children and often accompanied by child sexual offending (CSO).
Consequently, it is important to address the understanding of executive
dysfunctions that may increase the probability of CSO. Moreover, this research
field has been lacking to disentangle executive deficits associated with
pedophilia (as a deviant sexual preference) from those associated with CSO (as a
deviant sexual behavior). METHODS: The German multi-sided research network NeMUP
offers the opportunity to overcome these limitations. By applying the Cambridge
Automated Neuropsychological Test Battery in four carefully matched groups of
men: (1) pedophiles with (N=45) and (2) without (N=45) a history of sexual
offending against children; (3) child molesters without pedophilia (N=19), and
(4) non-offending controls (N=49), we were able to analyze executive functioning
in pedophilia and CSO independently. RESULTS: Both CSO groups as compared to both
non-CSO groups exhibited worsened response inhibition ability. However, only non
pedophilic offenders showed additionally disabled strategy use ability. Regarding
set-shifting abilities, the P+CSO group showed the best performance. We also
found that performances were affected by age: only in pedophiles, response
inhibition worsened with age, while age-related deficits in set-shifting
abilities were restricted to non-pedophilic participants. The latter also
differentiated between both sexual preference groups. CONCLUSIONS: Our results
are the first to demonstrate that executive dysfunctions are related to offense
status rather than pedophilic preference. Furthermore, there was evidence for
differentiating age and performance correlations between pedophiles and non
pedophiles, which warrants further investigation. (JINS, 2017, 23, 460-470).
PMID- 28511727
TI - Rejection Sensitivity as a Moderator of Psychosocial Outcomes Following Pediatric
Traumatic Brain Injury.
AB - OBJECTIVES: The current study examines whether psychosocial outcomes following
pediatric traumatic brain injury (TBI) vary as a function of children's rejection
sensitivity (RS), defined as their disposition to be hypersensitive to cues of
rejection from peers. METHODS: Children ages 8-13 with a history of severe TBI
(STBI, n=16), complicated mild/moderate TBI (n=35), or orthopedic injury (OI,
n=49) completed measures assessing self-esteem and RS on average 3.28 years post
injury (SD=1.33, range=1.25-6.34). Parents reported on their child's emotional
and behavioral functioning and social participation. RESULTS: Regression analyses
found moderation of group differences by RS for three outcomes: social
participation, self-perceptions of social acceptance, and externalizing behavior
problems. Conditional effects at varying levels of RS indicated that
externalizing problems and social participation were significantly worse for
children with STBI at high levels of RS, compared to children with OI. Social
participation for the STBI group remained significantly lower than the OI group
at mean levels of RS, but not at low levels of RS. At high levels of RS, self
perceptions of social acceptance were lower for children with moderate TBI
compared to OI, but group differences were not significant at mean or low levels
of RS. No evidence of moderation was found for global self-worth, self
perceptions of physical appearance or athletic ability, or internalizing
problems. CONCLUSIONS: The findings highlight the salient nature of social
outcomes in the context of varying levels of RS. These findings may have
implications for the design of interventions to improve social outcomes following
TBI. (JINS, 2017, 23, 451-459).
PMID- 28511728
TI - Birth weight interacts with a functional variant of the oxytocin receptor gene
(OXTR) to predict executive functioning in children.
AB - Genetic variation in the oxytocin receptor gene (OXTR) is associated with several
psychiatric conditions characterized by deficits in executive functioning (EF). A
specific OXTR variant, rs2254298, has previously been associated with brain
functioning in regions implicated in EF. Moreover, birth weight variation across
the entire range is associated with individual differences in cortical structure
and function that underlie EF. This is the first study to examine the main and
interactive effect between rs2254298 and birth weight on EF in children. The
sample consisted of 310 children from an ongoing longitudinal study. EF was
measured at age 4.5 using observational tasks indexing working memory, cognitive
flexibility, and inhibitory control. A family-based design that controlled for
population admixture, stratification, and nongenomic confounds was employed. A
significant genetic association between rs2254298 and EF was observed, with more
copies of the major allele (G) associated with higher EF. There was also a
significant interaction between rs2254298 and birth weight, such that more copies
of the major allele in combination with higher birth weight predicted better EF.
Findings suggest that OXTR may be associated with discrete neurocognitive
abilities in childhood, and these effects may be modulated by intrauterine
conditions related to fetal growth and development.
PMID- 28511729
TI - Juicy Conceptualizations: Increasing Alliance Through Attending to Client
Metaphoric Language.
AB - BACKGROUND: There is increasing interest in the use of metaphor in cognitive
behaviour therapy. Experts advocate bringing client metaphors into case
conceptualizations, but there is little empirical research to support this. AIMS:
This study evaluated the effect of training 12 therapists to attend to client
metaphors and bring them into case conceptualizations. METHOD: Pre- and post
training role-played therapy sessions were conducted and video-recorded. Alliance
was rated by role play 'clients' and an external expert rated the quality of the
sessions and of the shared conceptualizations. RESULTS: There were significant
increases in some ratings of alliance, based on role play 'client' ratings and
external ratings of role plays of therapy sessions before and after training. The
greater the difference between therapist and 'client' on a measure of preference
for producing metaphor, the lower the rating of the session by the 'client' on
the Bond factor score of an alliance measure, the Working Alliance Inventory.
This result suggests that working metaphorically may be most effective when the
therapist and client have a similar degree of preference for speaking
metaphorically. CONCLUSION: This study provides preliminary support for the idea
that attending to client metaphors during conceptualization can be beneficial for
alliance.
PMID- 28511730
TI - Simulation in Canadian postgraduate emergency medicine training - a national
survey.
AB - OBJECTIVES: Simulation-based education (SBE) is an important training strategy in
emergency medicine (EM) postgraduate programs. This study sought to characterize
the use of simulation in FRCPC-EM residency programs across Canada. METHODS: A
national survey was administered to residents and knowledgeable program
representatives (PRs) at all Canadian FRCPC-EM programs. Survey question themes
included simulation program characteristics, the frequency of resident
participation, the location and administration of SBE, institutional barriers,
interprofessional involvement, content, assessment strategies, and attitudes
about SBE. RESULTS: Resident and PR response rates were 63% (203/321) and 100%
(16/16), respectively. Residents reported a median of 20 (range 0-150) hours of
annual simulation training, with 52% of residents indicating that the time
dedicated to simulation training met their needs. PRs reported the frequency of
SBE sessions ranging from weekly to every 6 months, with 15 (94%) programs having
an established simulation curriculum. Two (13%) of the programs used simulation
for resident assessment, although 15 (94%) of PRs indicated that they would be
comfortable with simulation-based assessment. The most common PR-identified
barriers to administering simulation were a lack of protected faculty time (75%)
and a lack of faculty experience with simulation (56%). Interprofessional
involvement in simulation was strongly valued by both residents and PRs.
CONCLUSIONS: SBE is frequently used by Canadian FRCPC-EM residency programs.
However, there exists considerable variability in the structure, frequency, and
timing of simulation-based activities. As programs transition to competency-based
medical education, national organizations and collaborations should consider the
variability in how SBE is administered.
PMID- 28511731
TI - Dietary nitrate and blood pressure: evolution of a new nutrient?
AB - Dietary nitrate is mainly obtained from vegetables, especially green leafy
vegetables and beetroot. As a result of early research, dietary nitrate is
currently viewed as a contaminant linked to increased risks of stomach cancer and
methaemoglobinaemia. Consequently, nitrate levels are restricted in certain
vegetables and in water supplies to ensure exposure levels remain below an
acceptable daily intake of 3.7 mg/kg per d. The average nitrate intake in the UK
is approximately 70 mg/d, although some population groups, such as vegetarians,
may consume three times that amount. However, recent studies in the last decade
suggest that dietary nitrate can significantly reduce systolic blood pressure via
the nitrate-nitrite-NO pathway. A small, downward shift in systolic blood
pressure across the population could significantly reduce the incidence of
hypertension and mortality from CVD such as stroke. Interestingly, vegetarians
tend to have lower levels of blood pressure than omnivores and epidemiological
studies suggest that vegetarians have lower risks of CVD. Recent evidence is
mainly focused on the acute effects of dietary nitrate supplementation and there
is a lack of data looking at the chronic effects of high nitrate consumption in
humans. Nevertheless, due to potential health benefits, some authors are
recommending that nitrate should be considered as a nutrient necessary for
health, rather than as a contaminant which needs to be restricted. This review
will discuss the emerging role of dietary nitrate in the control of blood
pressure and whether there is sufficient evidence to state that nitrate is a
'new' nutrient.
PMID- 28511732
TI - Outbreak of diarrhoea among participants of a triathlon and a duathlon on 12 July
2015 in Utrecht, the Netherlands.
AB - On 12 July 2015, a triathlon competition with 900 participants took place in
Utrecht, the Netherlands. An outbreak investigation was initiated after 56
participants reported health complaints. An online questionnaire was sent to 700
participants. Stool specimens from six participants and four water specimens were
collected from the swimming location. A total of 239 participants completed the
questionnaire (response rate: 34%), 73 (31%) of them met the case definition for
acute gastrointestinal illness (AGI). A total of 67% of the respondents were male
and the median age was 38 years. Almost half (42%) of swimmers reported health
complaints. Consumption of energy drinks and ingesting ?3 mouthfuls of canal
water were identified as risk factors for AGI among swimmers only (adjusted
relative risks (aRR) 1.6; 95% confidence intervals (CI) 1.0-2.5 and aRR 2.6; 95%
CI 1.5-4.8). The collected water specimens tested positive for norovirus
genogroup I and rotavirus and stool specimens tested positive for norovirus
genogroup II. Our findings indicate that the outbreak could have been caused by
exposure to norovirus during swimming. Swimmers should get information about the
health risks for making an informed choice about participating. For future
events, the organisers decided to change the swimming location from a canal to a
recreational lake.
PMID- 28511733
TI - Similarities and interactions between the ageing process and high chronic intake
of added sugars.
AB - In our societies, the proportions of elderly people and of obese individuals are
increasing. Both factors are associated with high health-related costs. During
obesity, many authors suggest that it is a high chronic intake of added sugars
(HCIAS) that triggers the shift towards pathology. However, the majority of
studies were performed in young subjects and only a few were interested in the
interaction with the ageing process. Our purpose was to discuss the metabolic
effects of HCIAS, compare with the effects of ageing, and evaluate how
deleterious the combined action of HCIAS and ageing could be. This effect of
HCIAS seems mediated by fructose, targeting the liver first, which may lead to
all subsequent metabolic alterations. The first basic alterations induced by
fructose are increased oxidative stress, protein glycation, inflammation,
dyslipidaemia and insulin resistance. These alterations are also present during
the ageing process, and are closely related to each other, one leading to the
other. These basic alterations are also involved in more complex syndromes, which
are also favoured by HCIAS, and present during ageing. These include non
alcoholic fatty liver disease, hypertension, neurodegenerative diseases,
sarcopenia and osteoporosis. Cumulative effects of ageing and HCIAS have been
seldom tested and may not always be strictly additive. Data also suggest that
some of the metabolic alterations that are more prevalent during ageing could be
related more with nutritional habits than to intrinsic ageing. In conclusion, it
is clear that HCIAS interacts with the ageing process, accelerates the
accumulation of metabolic alterations, and that it should be avoided.
PMID- 28511734
TI - Sleeping with one eye open: loneliness and sleep quality in young adults.
AB - BACKGROUND: Feelings of loneliness are common among young adults, and are
hypothesized to impair the quality of sleep. In the present study, we tested
associations between loneliness and sleep quality in a nationally representative
sample of young adults. Further, based on the hypothesis that sleep problems in
lonely individuals are driven by increased vigilance for threat, we tested
whether past exposure to violence exacerbated this association. METHOD: Data were
drawn from the Environmental Risk (E-Risk) Longitudinal Twin Study, a birth
cohort of 2232 twins born in England and Wales in 1994 and 1995. We measured
loneliness using items from the UCLA Loneliness Scale, and sleep quality using
the Pittsburgh Sleep Quality Index. We controlled for covariates including social
isolation, psychopathology, employment status and being a parent of an infant. We
examined twin differences to control for unmeasured genetic and family
environment factors. RESULTS: Feelings of loneliness were associated with worse
overall sleep quality. Loneliness was associated specifically with subjective
sleep quality and daytime dysfunction. These associations were robust to controls
for covariates. Among monozygotic twins, within-twin pair differences in
loneliness were significantly associated with within-pair differences in sleep
quality, indicating an association independent of unmeasured familial influences.
The association between loneliness and sleep quality was exacerbated among
individuals exposed to violence victimization in adolescence or maltreatment in
childhood. CONCLUSIONS: Loneliness is robustly associated with poorer sleep
quality in young people, underscoring the importance of early interventions to
mitigate the long-term outcomes of loneliness. Special care should be directed
towards individuals who have experienced victimization.
PMID- 28511735
TI - Addenbrooke's cognitive examination-revised: normative and accuracy data for
seniors with heterogeneous educational level in Brazil.
AB - BACKGROUND: Several cognitive tools have been developed aiming to diagnose
dementia. The cognitive battery Addenbrooke's Cognitive Examination - Revised
(ACE-R) has been used to detect cognitive impairment; however, there are few
studies including samples with low education. The aim of the study was to provide
ACE-R norms for seniors within a lower education, including illiterates. An
additional aim was to examine the accuracy of the ACE-R to detect dementia and
cognitive impairment no dementia (CIND). METHODS: Data originated from an
epidemiological study conducted in the municipality of Tremembe, Brazil. The
Brazilian version of ACE-R was applied as part of the cognitive assessment in all
participants. Of the 630 participants, 385 were classified as cognitively normal
(CN) and were included in the normative data set, 110 individuals were diagnosed
with dementia, and 135 were classified as having CIND. RESULTS: ACE-R norms were
provided with the sample stratified into age and education bands. ACE-R total
scores varied significantly according to age, education, and sex. To distinguish
CN from dementia, a cut-off of 64 points was established (sensitivity 91%,
specificity 76%) and to differentiate CN from CIND the best cut-off was 69 points
(sensitivity 73%, specificity 65%). Cut-off scores varied according to the
educational level. CONCLUSIONS: This study offers normative and accuracy
parameters for seniors with lower education and it should expand the use of the
ACE-R for this population segment.
PMID- 28511736
TI - Dietary salt intake in the Australian population.
AB - OBJECTIVE: To update the estimate of mean salt intake for the Australian
population made by the Australian Health Survey (AHS). DESIGN: A secondary
analysis of the data collected in a cross-sectional survey was conducted.
Estimates of salt intake were made in Lithgow using the 24 h diet recall
methodology employed by the AHS as well as using 24 h urine collections. The data
from the Lithgow sample were age- and sex-weighted, to provide estimates of daily
salt intake for the Australian population based upon (i) the diet recall data and
(ii) the 24 h urine samples. SETTING: Lithgow, New South Wales, Australia.
SUBJECTS: Individuals aged >=20 years residing in Lithgow and listed on the 2009
federal electoral roll. RESULTS: Mean (95 % CI) salt intake estimated from the 24
h diet recalls was 6.4 (6.2, 6.7) g/d for the Lithgow population compared with a
corresponding figure of 6.2 g/d for the Australian population derived from the
AHS. The corresponding estimate of salt intake for Lithgow adults based upon the
24 h urine collections was 9.0 (8.6, 9.4) g/d. When the age- and sex-specific
estimates of salt intake obtained from the 24 h urine collections in the Lithgow
sample were weighted using Australian census data, estimated salt intake for the
Australian population was 9.0 (8.6, 9.5) g/d. Further adjustment for non-urinary
Na excretion made the best estimate of daily salt intake for both Lithgow and
Australia about 9.9 g/d. CONCLUSIONS: The dietary recall method used by the AHS
likely substantially underestimated mean population salt consumption in
Australia.
PMID- 28511737
TI - Suicide in older adults: differences between the young-old, middle-old, and
oldest old.
AB - BACKGROUND: In the limited research into suicides in older adults, they have been
treated as a homogenous group without distinguishing between different age
groups. This study aimed to compare differences in sociodemographic variables,
recent life events, and mental and physical illnesses between three age groups
within older adults who died by suicide: young-old (65-74 years), middle-old (75
84 years), and oldest old (85 years and over) in Queensland, Australia, during
the years 2000-2012 (N = 978). METHODS: The Queensland Suicide Register was
utilized for the analysis. Annual suicide rates were calculated. Odds ratios with
95% confidence intervals and chi 2 tests for trend were calculated to examine
differences between the three groups. RESULTS: Suicide rates were increasing with
age for males, but not for females. Hanging and firearms were the predominant
methods of suicides. However, suffocation by plastic bag and drowning as suicide
methods increased with age, in contrast firearms and explosives decreased with
age. Overall, psychiatric problems, suicidal behavior, legal and financial
stressors, and relationship problems decreased significantly with age, meanwhile
physical conditions and bereavement increased with age. CONCLUSION: Suicide
across older adulthood is not a homogenous phenomenon. Our findings showed
significant differences in the prevalence of potential risk factors within the
three different age groups considered. To prevent suicide in older adults would
require targeting specific factors for each subgroup while using holistic and
comprehensive approaches.
PMID- 28511738
TI - Positive psychology outcome measures for family caregivers of people living with
dementia: a systematic review.
AB - BACKGROUND: Family caregivers of people living with dementia can have both
positive and negative experiences of caregiving. Despite this, existing outcome
measures predominately focus on negative aspects of caregiving such as burden and
depression. This review aimed to evaluate the development and psychometric
properties of existing positive psychology measures for family caregivers of
people living with dementia to determine their potential utility in research and
practice. METHOD: A systematic review of positive psychology outcome measures for
family caregivers of people with dementia was conducted. The databases searched
were as follows: PsychINFO, CINAHL, MEDLINE, EMBASE, and PubMed. Scale
development papers were subject to a quality assessment to appraise psychometric
properties. RESULTS: Twelve positive outcome measures and six validation papers
of these scales were identified. The emerging constructs of self-efficacy,
spirituality, resilience, rewards, gain, and meaning are in line with positive
psychology theory. CONCLUSIONS: There are some robust positive measures in
existence for family caregivers of people living with dementia. However, lack of
reporting of the psychometric properties hindered the quality assessment of some
outcome measures identified in this review. Future research should aim to include
positive outcome measures in interventional research to facilitate a greater
understanding of the positive aspects of caregiving and how these contribute to
well-being.
PMID- 28511739
TI - Self-Critical Thinking and Overgeneralization in Depression and Eating Disorders:
An Experimental Study.
AB - BACKGROUND: Self-critical thinking is common across psychological disorders. This
study hypothesized that it may play an important role in 'overgeneralization',
the process of drawing general implications from an isolated negative experience.
AIMS: To explore the impact of two experimental tasks designed to elicit self
critical thoughts on the endorsement of general negative self-views of clinical
and non-clinical populations. METHOD: Three groups (depression, eating disorders
and non-clinical controls), completed standardized questionnaires and the two
tasks. Participants rated their self-critical thinking and general negative self
beliefs before and after each task. RESULTS: Following a failure experience, both
clinical groups showed a greater increase in general negative self-views compared
with controls, indicating greater overgeneralization. Both habitual and increases
in state self-critical thinking were associated with overgeneralization while
negative perfectionism was not. Overgeneralization was more strongly associated
with post-task reduced mood than self-criticism. CONCLUSIONS: Self-critical
thinking may be an important factor in the process of overgeneralization, and the
increase in general negative self-views may be particularly crucial for lowering
of mood.
PMID- 28511741
TI - Influenza detection and prediction algorithms: comparative accuracy trial in
Ostergotland county, Sweden, 2008-2012.
AB - Methods for the detection of influenza epidemics and prediction of their progress
have seldom been comparatively evaluated using prospective designs. This study
aimed to perform a prospective comparative trial of algorithms for the detection
and prediction of increased local influenza activity. Data on clinical influenza
diagnoses recorded by physicians and syndromic data from a telenursing service
were used. Five detection and three prediction algorithms previously evaluated in
public health settings were calibrated and then evaluated over 3 years. When
applied on diagnostic data, only detection using the Serfling regression method
and prediction using the non-adaptive log-linear regression method showed
acceptable performances during winter influenza seasons. For the syndromic data,
none of the detection algorithms displayed a satisfactory performance, while non
adaptive log-linear regression was the best performing prediction method. We
conclude that evidence was found for that available algorithms for influenza
detection and prediction display satisfactory performance when applied on local
diagnostic data during winter influenza seasons. When applied on local syndromic
data, the evaluated algorithms did not display consistent performance. Further
evaluations and research on combination of methods of these types in public
health information infrastructures for 'nowcasting' (integrated detection and
prediction) of influenza activity are warranted.
PMID- 28511740
TI - The association between cognitive decline and incident depressive symptoms in a
sample of older Puerto Rican adults with diabetes.
AB - BACKGROUND: Older Puerto Rican adults have particularly high risk of diabetes
compared to the general US population. Diabetes is associated with both higher
depressive symptoms and cognitive decline, but less is known about the
longitudinal relationship between cognitive decline and incident depressive
symptoms in those with diabetes. This study investigated the association between
cognitive decline and incident depressive symptoms in older Puerto Rican adults
with diabetes over a four-year period. METHODS: Households across Puerto Rico
were visited to identify a population-based sample of adults aged 60 years and
over for the Puerto Rican Elderly: Health Conditions study (PREHCO); 680
participants with diabetes at baseline and no baseline cognitive impairment were
included in analyses. Cognitive decline and depressive symptoms were measured
using the Mini-Mental Caban (MMC) and Geriatric Depression Scale (GDS),
respectively. We examined predictors of incident depressive symptoms (GDS >= 5 at
follow-up but not baseline) and cognitive decline using regression modeling.
RESULTS: In a covariate-adjusted logistic regression model, cognitive decline,
female gender, and greater diabetes-related complications were each significantly
associated with increased odds of incident depressive symptoms (p < 0.05). In a
multiple regression model adjusted for covariates, incident depressive symptoms
and older age were associated with greater cognitive decline, and higher
education was related to less cognitive decline (p < 0.05). CONCLUSIONS: Incident
depressive symptoms were more common for older Puerto Ricans with diabetes who
also experienced cognitive decline. Efforts are needed to optimize diabetes
management and monitor for depression and cognitive decline in this population.
PMID- 28511743
TI - Health and Economic Burden of Skin Melanoma in Croatia - Cost-of-illness Study.
AB - Melanoma incidence is increasing, especially in the younger population. The aim
of this study was to investigate the cost of this disease in the Croatian
population and to identify costs through types of care and types of costs. The
secondary goal was to estimate the prevalence of certain types of melanoma (as
well as staging distribution) and to connect each stage and its prevalence in
Croatia to related costs. A cost-of-illness analysis was performed, mainly
including direct costs (monitoring, drugs, primary health care services,
hospitalizations, and diagnostics). The calculations were based on data collected
from Sestre milosrdnice University Hospital Center in Zagreb and from Cancer
Registry Data. The number of patients with melanoma was calculated using the
Markov model for melanoma staging and 5-year survival. The estimated total
prevalence of melanoma in 2011 in Croatia was 2,180. The total cost of melanoma
was estimated to 1,063,488 EUR, with 46% used for hospitalization and
chemotherapy, 10% for dermatoscopy, and the remaining 17% being monitoring costs.
The average cost per patient was estimated to range between 98 and 4,333 EUR
depending on the stage of the disease. The cost of melanoma in the adult
population in Croatia in a one-year timeframe accounted for as much as 0.04% of
the total Croatian national health care budget for 2011. Study findings indicate
the need for a clear strategy to achieve regular screening in order to detect the
disease at an early stage.
PMID- 28511742
TI - Predictors for routine admission to paediatric intensive care for post
supraglottoplasty laryngomalacia patients.
AB - OBJECTIVES: Supraglottoplasty for the treatment of laryngomalacia has little
current evidence regarding post-operative care. Our study aimed to: (1)
retrospectively assess what proportion of patients required paediatric intensive
care unit level of care; (2) identify pre-operative predictive factors common to
these cases; and (3) report patient outcomes at six weeks' follow up. METHODS: A
10-year retrospective case series analysis was conducted of all patients
diagnosed with laryngomalacia and subsequently treated with supraglottoplasty.
Paediatric intensive care unit level of care was defined as the need for
intubation or tracheostomy, positive pressure ventilation, multiple doses of
nebulised adrenaline, and oxygen dependency beyond 12 hours. RESULTS: Forty-two
patients (19 males, 23 females) were identified; 28.5 per cent of cases met our
criteria for paediatric intensive care unit level of care. A low pre-operative
oxygen saturation was the only significant risk factor that predicted a future
need for paediatric intensive care unit level of care (p = 0.0008). CONCLUSION:
This is the first study published in the UK to suggest the importance of pre
operative oxygen saturation as a predictor of a future need for paediatric
intensive care unit level of care.
PMID- 28511744
TI - Correlation of Antibodies against Desmogleins 1 and 3 with Indirect
Immunofluorescence and Disease Activity in 72 Patients with Pemphigus Vulgaris.
AB - The enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence
(IIF) have both been used for testing of antibodies to desmogleins 1 and 3 (anti
Dsg1 and anti-Dsg3) and for the serologic diagnosis of pemphigus. IIF values and
antibody concentrations and profile do not always correlate with a specific
clinical phenotype and with the disease activity. The purpose of the present
study was to correlate the clinical phenotype of patients with pemphigus vulgaris
(PV) and the disease activity with anti-Dsg1 and anti-Dsg3 antibodies and IIF
titers. A total of 72 patients with PV underwent ELISA serum testing for the
presence and titers of anti-Dsg1 and anti-Dsg3 and IIF which were correlated with
the severity of the disease (evaluated using the Pemphigus Disease Area Index,
PDAI), clinical phenotype, and clinical course. In 79.2% patients there was a
perfect correlation between the clinical phenotype and antibody profiles; in
20.8% patients, clinical features and antigenic findings were discordant. A
statistically significant correlation was found between disease activity and a)
anti-Dsg3 and anti-Dsg1 concentrations (Rho=0.679, P<0.001 and Rho=0.363, P=0.02,
respectively) and b) IIF titers (Rho=0.426, P<0.01), as well between IIF titers
and anti-Dsg3 and anti-Dsg1 antibodies (Rho=0.742, P<0.01 and Rho=0.372, P=0.02,
respectively). This study supports the previous observations that the disease
severity in most patients with pemphigus correlates with IIF titers, which in
turn is determined by the quantities of Dsg1 and Dsg3 antibodies, as well as the
previous observation that the clinical phenotype and antibody profile are not
always in correlation.
PMID- 28511745
TI - Lupus Band Test in Patients with Borderline Systemic Lupus Erythematosus with
Discoid Lesions.
AB - Patients with lupus erythematosus (LE) that have discoid lesions who fulfill the
four diagnostic criteria of systemic lupus erythematosus (SLE) with only
mucocutaneous findings and antinuclear antibody (ANA) positivity were classified
as borderline SLE in the literature. Objective of this study was to determine the
place of borderline SLE with discoid lesions on the LE spectrum according to the
lupus band test (LBT). Lesional and sun-protected non-lesional (SPNL) skin LBTs
of 94 patients with LE that had discoid lesions were retrospectively evaluated.
Firstly, patients were divided into two main groups: discoid LE (DLE; group A)
and SLE (Group B); three subgroups were then classified as DLE (Group A),
borderline SLE (Group B1) and SLE (Group B2) using another method. Each group had
its own comparisons. Immunoreactant (IR) deposition was observed on the lesional
skin in all patients and on the SPNL skin in 42 (44.7%). In patients with
borderline SLE, the deposition of IgM was lower on the lesional LBTs, whereas
isolated IgG was higher than SLE; thus, it shows similarity with DLE.
Additionally, it was also closer to DLE because of the low deposition of C3,
multiple IRs, and a double conjugate of IRs on the SPNL skin. However, it showed
similarity with SLE in the high percentage of LBT positivity and more
immunoglobulin M (IgM) and immunoglobulin G (IgG) deposition on the SPNL skin.
The deposition of multiple conjugates on SPNL skin in patients with LE with
discoid lesions may reflect systemic involvement. Despite the fact that LBT
positivity on SPNL skin in borderline SLE was higher than DLE, less deposition of
multiple conjugates compared to SLE indicates that the classification of
borderline SLE with discoid lesions in the LE spectrum is questionable.
PMID- 28511746
TI - Two Ultrasonographic Patterns in Maculopapular Cutaneous Mastocytosis: A
Preliminary Report.
AB - Maculopapular cutaneous mastocytosis (MPCM) is a variant of cutaneous
mastocytosis resulting from abnormal accumulation of mast cells in dermal
tissues. Ultrasonography is a contemporary, safe, non-invasive, and real-time
diagnostic method. High-frequency ultrasonography (HFUS) utilizes probes emitting
frequencies of 20 MHz and higher, visualizing and measuring areas of healthy and
lesional skin in various dermatologic conditions. We examined 4 patients with
MPCM using a taberna pro medicumTM (Germany) device. We present 2 characteristic
ultrasonographic patterns of MPCM lesions. Three subjects presented with an
abnormal, widened, and hypoechogenic area representing the dermis. One subject
demonstrated an anechogenic fusiform structure below the epidermis that
represented a localized pattern of infiltrate. This patient responded better to
psoralen and ultraviolet A radiation (PUVA) therapy than the other subjects. Our
research implies that HFUS may be used as an additional method in evaluating skin
lesions in MPCM.
PMID- 28511747
TI - Red Blood Cell Distribution Width is a Reliable Marker of Inflammation in Plaque
Psoriasis.
AB - Psoriasis is a systemic inflammatory disease accepted as an independent risk
factor for cardiovascular diseases (CVD). Elevated levels and correlation of red
cell distribution width (RDW) with inflammatory markers has recently been shown
in studies investigating CVD risk and prognosis in rheumatoid arthritis and
ankylosing spondylitis. The aim of this study was to evaluate levels and
correlation of RDW with inflammatory markers in patients with plaque psoriasis.
Data including demographics, disease severity indices, laboratory parameters, and
bioelectrical impedance analysis was collected from medical charts of patients
who were diagnosed with plaque psoriasis at the Hacettepe University Department
of Dermatology between March 2014 and August 2015. Patients were evaluated for
major CVD risk factors defined by international guidelines. 199 patients with
psoriasis and 73 volunteers were included. Patients had statistically significant
higher values of metabolic age, visceral fat rating, body-mass index (BMI), red
blood cells (RBC), white blood cells (WBC), red blood cell distribution width
(RDW), alanine aminotransferase (ALT), uric acid, low-density lipoprotein (LDL),
and C-reactive protein (CRP) (p=0.044, p=0.047,p=0.029, p= 0.005, p=0.02, p<0,01,
p=0.001, p=0,016, p=0,014, p<0.01). A statistically significant relationship and
positive correlation between RDW and CRP levels was found in the patient group
(p=0.01, r=0.396). Patients without major CVD risk factors (n=79) had
significantly higher values of RDW, LDL, and CRP (p=0.01, p=0.031, p=0.03,
respectively). Patients with psoriasis who had one or more CVD risk factors
(n=120) had significantly higher values of BMI, RDW, thrombocytes, ALT, and CRP
(p=0.038, p=0.01, p=0.017, p=0.02, p=0.01, respectively). RDW, which is elevated
as well as CRP, reflects the systemic inflammatory burden and can be used for
prediction of CVD in psoriasis. In fact, patients with psoriasis who do not have
any major CVD risk factors still have high levels of CRP and RDW, supporting the
hypothesis that psoriatic inflammation itself can simultaneously cause CRP and
RDW elevation. Coexistence of CVD risk factors is associated with ALT elevation
since additional CVD risk factors may predict psoriatic comorbidities such as non
alcoholic fatty liver disease.
PMID- 28511748
TI - Stress and Coping in Patients with Clinical Manifestations of Human
Papillomavirus.
AB - Stressful life events in response to a psychosocial trigger have been reported to
negatively affect the course of infections. This study was based on patients with
clinical manifestations of human papillomavirus (HPV) infection and a control
group of patients with psoriasis who were admitted over a period of one year to
the Dermatology Department of Karlovac General Hospital. A total of 122 patients
participated in the study, either with a confirmed diagnosis of clinical
manifestations of HPV infection (n=66) or in a psoriasis control group (n=56).
The aim of this study was to determine which coping strategies are used in
patients with clinical manifestations of HPV infection. We used the Recent Life
Changes Questionnaire and Brief COPE test for stress evaluation. There were no
statically significant differences between adaptive and maladaptive coping
strategies comparing patients with HPV and a control group. The difference in
specific coping strategies between HPV and control groups showed that self-blame
and planning strategies were statistically significantly more common in the HPV
group. Patients with HPV with genital warts used maladaptive coping statistically
significantly more than patients with non-genital localization of HPV. Patients
with HPV who had a higher score of life stress events used maladaptive coping
statistically significantly more than patients with a lower life stress events
score. The results point to the need for patients with HPV with genital
localization and high numbers of stress events to learn how to cope with stress,
enabling them to take action and change their ways of coping. There is also a
need to integrate psychological intervention into standard care protocols of
dermatologic diseases.
PMID- 28511749
TI - Microinvasive Radial Growth Phase of Cutaneous Melanoma: A Histopathological and
Immunohistochemical Study with Diagnostic Implications.
AB - Cutaneous melanoma (M) can develop through two progression phases: the radial
growth phase of M (RGPM) and the vertical one. This distinction has a practical
relevance in defining lesions with potential for a metastatic course. We analyzed
the morphological attributes (intraepidermal proliferation type, inflammatory
infiltrate, mitogenicity, Breslow thickness, Clark level, ulceration) and the
immunohistochemical profile (S100, Melan A, HMB45, p16INK4a, CD117, Ki67, Cyclin
D1, E Cadherin, Podoplanin) of 12 microinvasive RGPMs in absence of regression,
with almost 10 years of follow-up. Immunohistochemistry (IHC) revealed that S100,
Melan A, and HMB45 maintain a high expression in M cells in both epidermal and
dermal compartments. Interestingly, an overexpression of p16INK4a in the nests of
dermal microinvasion has been ascertained in all our cases. On the other hand, we
found an attenuation of expression for CD117, Ki67, Cyclin D1, and E Cadherin in
the migration phase from the epidermis to dermis. Each phase in M progression
appears characterized by a specific immunohistochemical profile, as a result of
molecular alterations. The long-term follow-up of our case series showed that
microinvasive RGPM without regression is not tumorigenic and is devoid of
metastatic potential; therefore, its accurate categorization is important.
Conversely, microinvasive RGPM with regression should be classified as
melanocytic tumor with uncertain biological potential. IHC for p16INK4a can be
helpful in the diagnosis of microinvasive M on challenging cutaneous biopsies.
Moreover, it can be applied as an immunohistochemical discriminator to
distinguish microinvasive RGPM from in situ RGPM and microinvasive RGPM from
dysplastic nevi.
PMID- 28511750
TI - The Prevalence of Penile Pearly Papules among Young Men.
AB - The aim of this study was to determine the prevalence of pearly penile papules
(PPP) among young men in Eskisehir, Turkey. This was a prospective, non
randomized, cross-sectional study. From December 2014 to September 2015, 2613
consecutive male patients who were referred to the dermatology outpatient clinic
were included in the study. Patients were inspected for the presence of PPP,
localization, and association with human papilloma virus (HPV). A total of 2613
patients were included in the study. The average age of the patients was 21.33+/
2.08 (mean +/- Standard Deviation (SD); ranging from 18 to 24) years. All of the
patients were white and circumcised men. Of the 2613 patients, 449 (17.18%) PPP
were observed. PPP were localized on the corona of the glans penis (100%),
coronal sulcus (18.9%), frenulum (15.1%), ventral shaft (5.3%), and dorsal shaft
of the penis (2.4%). Of the 449 patients with PPP, 23 (5.3%) underwent treatment;
73 (16.2%) would consider removal, 7 (1.5%) had a previous treatment for HPV, and
5 (1.1%) had HPV. PPP are encountered very commonly in the pubertal age in boys
and young men. All medical practitioners should be familiar with PPP. Their
similarity to genital warts may generate a false apprehension of venereal disease
and may lead to unwanted and hazardous treatments. Therefore, better health
education is needed.
PMID- 28511751
TI - Aging - What Do We Know?
AB - Skin aging is a combination of reduction in the biological activity of cells, a
slowing down of regenerative processes, and a loss of resistance to environmental
factors. Genetics, lifestyle, and hormones significantly affect proper
functioning of the skin. The aim of this article was to present the current
knowledge about aging processes and concurrent therapies which can influence skin
aging.
PMID- 28511752
TI - Biosimilars: An Update on Clinical Trials (Review of Published and Ongoing
Studies).
AB - Biosimilars represent a new trend in the treatment of many immune-mediated
inflammatory diseases. Regulatory requirements for approval of biosimilars are
different from those of originators and rely mostly on the evidence generated
from bioequivalence studies and in particular from RCTs. Our goal in this review
was to search for relevant studies from randomized controlled trials on the
biosimilars adalimumab, etanercept, infliximab and ustekinumab compared with
their reference medication (publication in Medline) and ongoing studies in
clinical trial registries. For infliximab biosimilars, we found data on patients
with ankylosing spondylitis rheumatoid arthritis indicating no clinically
relevant differences regarding efficacy and safety, as well as data on
inflammatory bowel diseases and psoriasis. In addition, three registered studies
of adalimumab biosimilars and just one study of an etanercept biosimilar were
being carried out in patients with psoriasis. Ongoing studies on adalimumab,
etanercept, and infliximab biosimilars in patients with rheumatoid arthritis were
also identified. The conclusion seems to be that there are only 4 clinical trials
on psoriasis (3 for the adalimumab biosimilar and 1 for etanercept biosimilar)
and 1 clinical trial for Pso, CD, UC, RA, and AS (with the Infliximab
biosimilar). Thus, the real and unique advantage of biosimilars is the low price
derived from the special design studies despite the high technology used in
fabrication process. Although not all ongoing biosimilar trials may have been
registered, the present situation in terms of registered trials is quite
unsatisfactory and provision of further clinical data and inclusion of patients
in patient registries will be crucial.
PMID- 28511754
TI - Antibiotic-induced Toxic Epidermal Necrolysis - A Case Report.
AB - Toxic epidermal necrolysis (TEN) is severe cutaneous hypersensitivity reaction
characterized by necrosis of the epidermis and detachment of the epidermis and
dermis that usually occurs as an idiosyncratic reaction to certain drugs. We
report the case of a patient admitted to our Intensive Care Unit after an above
the-knee amputation who developed toxic epidermal necrolysis, possibly resulting
from antibiotics therapy. Therapy included a combination of intravenous
immunoglobulin with gentle early debridement of necrotic skin areas followed by
wound coverage with a synthetic cover (Aquacel Ag(r)). This case report suggests
that intensive wound management together with intravenous immunoglobulin might be
beneficial in the treatment of patients with TEN.
PMID- 28511753
TI - Mycobacterium marinum Infection of the Hand in an Immunocompromised Aquarium
Hobbyist.
AB - M. marinum, a nontuberculous mycobacterium, is a rare human pathogen widely
distributed in the aquatic environment. In the previous century, epidemics took
place due to inadequately chlorinated swimming pool water. Nowadays the majority
of infections are acquired through contact of previously damaged skin with
contaminated fish tank water. We present a case of M. marinum infection of the
hand in an aquarium hobbyist which stayed unrecognized for 2 years. After
confirming the correct diagnosis, the patient was successfully treated with a
regiment containing clarithromycin and rifampicin. The aim of this paper is to
raise the awareness of the possibility of M. marinum infection when encountered
with non-healing nodular/verrucous/ulcerative lesions of the extremities.
PMID- 28511755
TI - Onychomadesis Following Cutaneous Vasculitis.
AB - Beau lines are transverse, band-like depressions extending from one lateral edge
of the nail to the other and affecting all nails at corresponding levels (1).
Onychomadesis is considered an extreme form of Beau line with subsequent
separation of the proximal nail plate from the nail bed. Both fall along a
spectrum of nail plate abnormalities that occur secondary to temporary nail
matrix arrest (NMA). Various systemic and dermatologic conditions have been
reported in association with onychomadesis (2-7) (Table 1). Nail changes can
affect all or some of the nails and both the fingernails and toenails; however,
fingernails are more frequently affected. The severity of the nail changes varies
depending on the underlying cause, its duration, and environmental factors (8).
We present a case of onychomadesis following cutaneous leukocytoclastic
vasculitis (CLCV). A 61-year-old woman presented to the Dermatology Clinic
complaining of a purpuric rash that began on her lower extremities and rapidly
progressed to her abdomen and upper extremities over the previous five days. Her
medical history was remarkable for hypertension and diet-controlled diabetes
mellitus. Her medications included enalapril, which she had been taking for the
past four years. On three consecutive days before the skin eruption, the patient
took oral diclofenac sodium for hip pain. A clinical examination revealed non
blanching petechial rash on the legs, abdomen, and upper limbs up to the elbow
(Figure 1, A) with leukocytoclastic vasculitis on biopsy (Figure 1, B). Direct
immunofluorescence was negative. Laboratory investigations revealed a white blood
cell count of 14.5 * 109/L with a normal differential count, and a platelet count
of 380 * 109/L. Westergren erythrocyte sedimentation rate was 65 mm/1st h, and C
reactive protein was at 8.5 mg/dL. Antinuclear antibodies, rheumatoid factor,
immune complexes, and cryoglobulinemia were negative, as were B and C hepatitis
virus serological tests. Her renal, cardiac, pulmonary, and abdominal exams were
normal. Diclofenac was discontinued due to a clinical suspicion of drug-induced
cutaneous vasculitis. The rash resolved in 2 weeks without treatment, leaving
post-inflammatory hyperpigmentation. Four weeks later, she presented with
painless, palpable grooves on all 10 fingernails (Figure 2). The grooves were 3
to 4 mm in width, at a similar distance from the proximal nail fold. There were
no signs of periungual inflammation. The patient denied any recent history of
trauma, unusual activities, or chemical exposure. Routine serum biochemistry and
hematology results were normal. Repeated potassium hydroxide preparations and
fungal cultures of the nail clippings were negative. A diagnosis of Beau lines
and onychomadesis was made. Nail changes were tolerable and did not require any
specific treatment. During the follow up, the Beau lines advanced with the linear
growth of the nails and disappeared (Figure 3 and 4). Four fingernails developed
complete nail shedding (onychomadesis). No toenail alterations were observed in
this period. A complete recovery of the nail plate surface was observed after 4
months. The nail matrix epithelium is formed by highly proliferating cells that
differentiate and keratinize to produce the nail plate. The nail matrix
epithelium is very susceptible to toxic noxae, and acute damage results in a
defective nail plate formation. Nail matrix arrest is a term used to describe a
temporary inhibition of the nail matrix proliferation that can present as Beau
lines and onychomadesis (8). The width of Beau lines relates to the duration of
the etiological agent. As the nail adheres firmly to the nail bed, the
onychomadesis remains latent for several weeks before leading to temporary
shedding (8,9). There are several proposed etiological mechanisms for NMA. NMA
associated with fever, severe infection, and major medical illnesses can be
explained by an inflammation of the matrix, periungual tissues, or digital blood
vessels (8); chemotherapy agents temporary inhibit the mitotic activity in nail
matrix (10); the detection of Coxackie virus in the shedding nail particle,
following hand, foot, and mouth disease, suggests that the viral replication
itself may directly damage the nail matrix (11). However, as nail changes are not
unique, it may be difficult to incriminate a single etiological agent. Our
patient presented with an onset of Beau lines seven weeks after the initial CLCV
lesions, which suggests that vasculitis might have acted as a trigger for NMA. As
the fingers were not affected by CLCV, an indirect effect of vasculitis is more
plausible. Leukocytoclastic vasculitis is a small-vessel inflammatory disease
mediated by a deposition of immune complexes. Thus, the circulating immune
complexes may be involved in the damage of nail bed microvasculature. Considering
that the patient had been receiving enalapril and diclofenac, it is less likely
that those drugs were involved in the pathogenesis of NMA. Enalapril was
continued, and the nail changes were resolved while patient was still on
enalapril. Furthermore, diclofenac is a widely prescribed drug and its
association with NMA is yet to be described in literature. We described a patient
who developed Beau lines and onychomadesis following cutaneous leukocytoclastic
vasculitis. This clinical observation can expand the spectrum of possible causes
of nail matrix arrest.
PMID- 28511756
TI - Nested Melanoma, a New Morphological Variant of Superficial Spreading Melanoma
with Characteristic Dermoscopic Features.
AB - A new morphological variant of superficial spreading melanoma (SSM) was first
described by Kutzner et al. (1) and named "melanoma composed exclusively or
predominantly of large nests"; it was later named "nested melanoma" (NM) (2,3).
Clinically, lesions are larger in diameter (>6 mm), mostly showing typical
clinical features of melanoma (the ABCD rule), and significantly different from
all other pigmented lesions (the "ugly duckling sign") (1). The majority of NM is
found on the trunk and limbs of patients older than 60 years (1-9). Dermoscopy
shows typical features of melanoma (asymmetry, irregular blotches, atypical
pigmented network, multicomponent structure, irregular dots, and globules)
followed by the "typical" dermoscopic finding of a globular pattern with globules
varying in shape, color, and distribution (1,3). It is known that flat nevi in
the elderly present with a reticular or structureless dermoscopic global pattern,
along with the fact that total nevi count decreases with advancing age due to
involution of nevi (4,5). Therefore, a globular pattern is uncommon in the
elderly, and this finding should always invoke a high suspicion of melanoma.
Histological diagnosis may be difficult because of the predominantly nested
pattern, and the condition may be confused histologically with a benign
junctional nevus (6). However, these large junctional nests of different sizes,
with bridging and cytonuclear atypias together with lesion asymmetry, are the
hallmark of this special kind of melanoma (6). Pathologically, NM presents with
large intraepidermal melanocytic nests, which are more or less the same size and
shape and equally distributed along the dermoepidermal junction, with a focal
tendency to confluence. Melanocytes in nests show moderate to significant
cytological atypia (1). Since most NMs were found on sun-damaged skin, solar
elastosis can be present. Pagetoid spread of atypical melanocytes along the
epidermis is rare, but may be found (1-3). In most case reports there was
discrepancy between clinical and dermoscopic features - both favoring melanoma -
and histopathology, which at first glance appeared nevoid (9). Although the
majority of analyzed NMs were in situ, an invasive dermal component was also
found. The atypical nevus in the elderly is an unstable nevus, and one variation
also observed is the hypercellular nested variant described by authors; these
have been reported as in situ nevoid melanomas, with cellular morphology usually
associated with crowded small-to-medium hyperchromatic melanocytes. The
progression of these atypical nested melanomas is often to a small cell (nevoid)
melanoma, which may become desmoplastic (9). Although the term "superficial
spreading melanoma" is appropriate for NM from a clinical perspective, at least
some of these tumors may be linked to an aberrant nevus pathway seen in elderly
individuals, explaining their unusual pattern resembling a bizarre nevus (9).
Additional tests can be performed due to clinicopathological discrepancy,
including confocal microscopy, immunohistochemistry, array comparative genomic
hybridization (aCGH), and in situ hybridization (FISH). Reflectance confocal
microscopy may be useful in cases of such difficult lesions in order to proceed
to surgical excision with more confidence, and can reveal the presence of dense
nests at the dermo-epidermal junction with cytologic atypia and pagetoid cells
(3,7). In confocal microscopy, a grossly regular clod pattern (at low
magnification) with atypical cells within nests (at higher magnification) was
found if the NM was in situ (3,7,9). aCGH showed multiple chromosomal aberrations
in all cases (1,2). Processing with the FISH technique showed a variation in
range from 40% to 87% FISH-positive NM, depending on different authors (1,2).
Once the diagnosis of NM is established, further treatment, including re
excision, is highly recommended (2). All the authors who described NM consider NM
a special variant of SSM in the elderly, and according to their opinion this
should lead to modification of histopathological criteria for SSM. We would
stress that the "elderly" criterion is not mandatory given the numerous cases
reported in people under 60 years of age (6). This is important and should
henceforth reduce misinterpretation of this variant of melanoma due to the
lesion's nevoid appearance (9). Dermoscopic criteria for NM should also be
established so clinicians consider NM in differential diagnosis, which would
further help the pathologist establish the correct diagnosis, since it is crucial
not to misdiagnose a malignant lesion. Dermoscopy is very helpful in all cases,
and globules are typically found in conjunction with other melanoma-specific
criteria (1,3).
PMID- 28511757
TI - Telehealth Overview: The Reality Check, Please.
AB - The trend lines and bar charts are marching up. Investors are investing, insurers
are extending coverage, health care systems are getting on board. But there at
some skunks at the telehealth garden party: research suggesting quality and
utilization problems and lingering uncertainty about reimbursement.
PMID- 28511758
TI - Possible Employee Wariness Stifles Telehealth's Acceptance.
AB - A lot hinges on this question: Do you feel comfortable getting a diagnosis or
being treated for a condition by someone on a screen?
PMID- 28511759
TI - Telehealth Business: Boom Times, but Profits May Wait.
AB - Investors are plowing millions into telehealth startups. Millennials could be
eager adopters. But these at early times and it may take years--and some
regulatory changes--for profits to materialize.
PMID- 28511760
TI - Some Thumbs Up, Some Down, on Telehealth Quality of Care.
AB - The study results are a mishmash; the methods, a work in progress. Antibiotic
prescribing is a trouble spot.
PMID- 28511761
TI - 'Telemental' Health Is Becoming the Norm.
AB - When it's time for a session, your therapist's face is on your phone or computer
instead of in the room. Telemental health doesn't mean the end of in-person
sessions, but it's increasingly part of the therapy mix.
PMID- 28511762
TI - Q&A: A Conversation with Henry DePhilips, MD: The Doctor in the Teladoc House.
AB - The CMO of Teladoc, one of the country's largest telemedicine providers,
certainly knows how to sing the praises of the industry, and handle devil's
advocate kind of questions as well. Most of Teledoc's customers are commercial
insurers and employers. Medicare? Not so much. Medicaid makes "perfect sense."
PMID- 28511763
TI - Are Insurers' Prior Authorization Rules Killing Opioid Addicts?
AB - Some insurers are changing their rules after the AMA and others said prior
authorization could result in treatment delays that can be deadly.
PMID- 28511765
TI - Basaglar, an Insulin 'Follow On,' Prepares To Do Battle With Lantus.
AB - At last, there's a biosimilar-like competitor in the U.S. insulin market. Can
Basaglar put some downward pressure on prices?
PMID- 28511764
TI - Telehealth Wave: Surf's Up for Fed, State Policymakers.
AB - If millions of Americans lose Medicaid or private health insurance coverage
because of the unACAing of American health care, telehealth may seem like a
gimmicky sideshow rather than a good-faith effort to bring health care into the
digital century.
PMID- 28511766
TI - Medimedia Poll of Managed Care Readers: Telehealth Gets a Warm Reception.
AB - In an online survey conducted in late February and early March, 37% of the 174
respondents rated the likelihood that telehealth will reduce health care costs as
high, and 50% favored laws and regulations that would encourage its adoption.
PMID- 28511767
TI - Finding the Virtue in Virtual Care.
AB - Virtual care offerings come with no shortage of complexities, but their potential
for value has many asking when, not if, to invest.
PMID- 28511768
TI - Telemedicine Seems To Work But Payment Creates a Disconnect.
AB - The cost savings go to payers, but providers often wind up footing the bill.
Value-based care could solve the problem.
PMID- 28511770
TI - Federal Per Capita Funding of Medicaid Deals a Wild Card to the States.
AB - Republicans say it brings efficiency and flexibility. Others see dire
consequences for beneficiaries.
PMID- 28511771
TI - Multiple priming instances increase the impact of practice-based but not verbal
code-based stimulus-response associations.
AB - Stimulus-response (S-R) associations, the basis of learning and behavioral
automaticity, are formed by the (repeated) co-occurrence of stimuli and responses
and render stimuli able to automatically trigger associated responses. The
strength and behavioral impact of these S-R associations increases with the
number of priming instances (i.e., practice). Here we investigated whether
multiple priming instances of a special form of instruction, verbal coding, also
lead to the formation of stronger S-R associations in comparison to a single
instance of priming. Participants either actively classified stimuli or passively
attended to verbal codes denoting responses once or four times before S-R
associations were probed. We found that whereas S-R associations formed on the
basis of active task execution (i.e., practice) were strengthened by multiple
priming instances, S-R associations formed on the basis of verbal codes (i.e.,
instruction) did not benefit from additional priming instances. These findings
indicate difference in the mechanisms underlying the encoding and/or retrieval of
previously executed and verbally coded S-R associations.
PMID- 28511773
TI - Psychiatric Patient Length of Stay in the Emergency Department Following Closure
of a Public Psychiatric Hospital.
AB - BACKGROUND: Psychiatric patient boarding in the emergency department (ED) is a
ubiquitous problem associated with increased morbidity and mortality. OBJECTIVE:
We evaluate the effect of closing a public psychiatric facility in a major
metropolitan area on the ED length of stay (LOS) of psychiatric patients.
METHODS: This was a retrospective chart review at two metropolitan EDs of all
patients assessed to require inpatient psychiatric hospitalization. The time of
arrival, time of disposition, time of transfer, insurance status, and accepting
facility type were collected prior to and following the closure of a local
inpatient psychiatric facility. RESULTS: We analyzed a total of 1107 patients
requiring inpatient psychiatric hospitalization, with 671 patients who presented
prior to the closure of the closest public psychiatric facility and 436 patients
that presented following the facility closure. Following hospital closure,
patients with private insurance (620 min before, 771 min after) and
Medicare/Medicaid (642 min before, 718 min after) had statistically significantly
longer ED LOS, as well as patients transferred to a private psychiatric hospital
(664 min prior, 745 min after). However, overall ED length of stay following
hospital closure for transfer of all psychiatric patients requiring inpatient
hospitalization was not found to be statistically significant (1017 min prior,
967 min after). CONCLUSION: There was a statistically significant increase in ED
LOS for patients with private insurance, Medicare/Medicaid, and for those
patients transferred to a private psychiatric facility following closure of a
public mental health hospital; however, overall, ED LOS was not increased for
patients transferred to an inpatient psychiatric facility. This study highlights
the significant impact that the closure of a single inpatient psychiatric
facility can have on nearby EDs. We hope to bring attention to the need for
increased psychiatric services during a time when there is a nationwide trend
toward the reduction of available inpatient psychiatric beds.
PMID- 28511774
TI - An Unusual Case of Flank Pain: More Than Just an Inguinal Hernia.
PMID- 28511772
TI - Transcoronary Concentration Gradient of microRNA-133a and Outcome in Patients
With Coronary Artery Disease.
AB - Circulating levels of microRNA (miR)-133a are increased in patients with coronary
atherosclerotic disease (CAD). Whether the cardiac release of this miR provides
any prognostic information in patients with CAD is currently unknown. We aimed to
investigate if changes in concentration of miR-133a trough the coronary
circulation may be associated with patients' cardiovascular outcome. We enrolled
111 patients (82 with stable CAD and 29 with acute coronary syndromes [ACS]) who
underwent coronary angiography. Circulating levels of miR-133a were measured
across the transcoronary circulation. Major adverse cardiac events (MACE: death,
nonfatal myocardial infarction, and need for revascularization) were recorded
through a median follow-up of 32 months. An increased transcoronary concentration
gradient of miR133a showed a significant association with overall rate of MACE at
follow-up in patients with both stable CAD and ACS (p = 0.011 and p = 0.002,
respectively). At the single end point-analysis, increased transcoronary
concentration gradients of miR133a were significantly associated with increased
rate of death in patients with ACS (p = 0.017) and with increased incidence of
new revascularization because of in-stent restenosis in patients with stable CAD
(p = 0.026). Kaplan-Meier curves showed a significantly worse event-free survival
in patients with greater transcoronary gradients of miR133a (p = 0.026 in stable
CAD group and p = 0.007 for ACS group). Nevertheless, these findings lost their
significance after adjustment for common cardiovascular risk factor and high
sensitivity troponin-T. In conclusions, the release of miR133a, as measured by
its transcoronary concentration gradient, is associated with a higher incidence
of MACE in patients with CAD, but it does not add significant prognostic
information compared with traditional prognostic biomarkers, therefore limiting
its potential usefulness in the clinical practice. Nevertheless, the differential
modulation of miR-133a release in the coronary circulation may reflect
pathophysiological mechanism involved in CAD progression and complications and
suggest a novel potential role for this miR in the development of in-stent
restenosis.
PMID- 28511775
TI - Alpha-fetoprotein is a significant prognostic factor for gastric cancer: Results
from a propensity score matching analysis after curative resection.
AB - BACKGROUND: Prognosis of alpha-fetoprotein positive gastric cancer (AFPP-GC)
remains elusive so far due to disparities in cohort size and baseline
characteristics in previous studies. A propensity score matching (PSM) analysis
as well as multivariable model was performed for unbiased evaluation of the
outcome in AFPGC. METHODS: Among 3034 gastric cancer patients who underwent
curative gastric cancer surgery (R0, M0) at the National Cancer Center, Korea
between 2002 and 2007, we identified 97 patients being positive for AFP either by
elevation of serum-AFP levels >10 MUg/L or by immunohistochemical staining. Due
to marked disparities in baseline characteristics and cohort size, propensity
score-matching was performed which matched 87 AFPP-GC patients to the same number
of AFP-negative gastric cancer (AFPN-GC) patients. Baseline characteristics were
compared using chi2-test. Survival curves were compared using the Kaplan-Meier
method and multivariable regression analysis was performed to evaluate the effect
of AFP-positivity while adjusting the effects of confounding variables. RESULTS:
AFPP-GC and AFPN-GC patients revealed marked disparities in patient cohorts.
After PSM, groups were balanced for age, sex, tumor size, BMI, tumor location,
grade of differentiation, presence of lymphatic vessel infiltration (LVI), Lauren
histologic type and stage distribution. In multivariable regression analysis of
the PSM-groups, only AFP-positivity and pathologic stage were predictive for
overall survival (HR 2.98, CI 95% {1.7-5.1}, p < 0.0001). Five-year-survival
rates were significantly worse for AFPP-GC patients (57.9% vs. 76.1%, p = 0.014).
Recurrence was significantly more frequent in AFPP-GC patients (p = 0.003).
CONCLUSION: AFP can be considered as an independent negative predictor of overall
and recurrence-free survival in patients with gastric cancer.
PMID- 28511776
TI - Radiation-induced cancer risk predictions in proton and heavy ion radiotherapy.
PMID- 28511777
TI - Expression of interleukin-1beta and interleukin-6 in leprosy reactions in
patients with human immunodeficiency virus coinfection.
AB - Previous studies suggest that coinfection of leprosy and human immunodeficiency
virus (HIV) does not decrease the frequency and intensity of leprosy reactions.
However, the immunological aspects of leprosy reactions in coinfected patients
remain obscure, with a limited number of studies showing contradictory results.
Observational study using tissue samples collected during leprosy reactions from
15 patients coinfected with leprosy and HIV and from 15 patients with leprosy
alone. Patients were part of a prior larger cohort study of leprosy patients with
and without HIV coinfection. Specific antibodies were used to detect IL-1beta and
IL-6 expression in skin biopsy tissue cells. IL-1beta and IL-6 expression was
similar between leprosy patients with and without HIV coinfection (p>0.05).
Coinfected and non-coinfected tissues showed similar levels of IL-1beta and IL-6
expression for type 1 reactions. A trend towards increased levels of IL-1beta and
IL-6 expression was observed in tissue from coinfected patients (p=0.0024). The
expression of IL-1beta and IL-6 during leprosy reactions did not differ
significantly between tissues obtained from leprosy patients with and without HIV
coinfection. Therefore, we conclude that HIV coinfection does not affect the
immunological pattern of leprosy reactions.
PMID- 28511778
TI - Elevated cranial ultrasound resistive indices are associated with improved
neurodevelopmental outcomes one year after pediatric cardiac surgery: A single
center pilot study.
AB - OBJECTIVE: To determine if a non-invasive, repeatable test can be used to predict
neurodevelopmental outcomes in patients with congenital heart disease. METHODS:
This was a prospective study of pediatric patients less than two months of age
undergoing congenital heart surgery at the Children's Health Children's Medical
Center at Dallas. Multichannel near-infrared spectroscopy (NIRS) was utilized
during the surgery, and ultrasound (US) resistive indices (RI) of the major
cranial vessels were obtained prior to surgery, immediately post-operatively, and
prior to discharge. Pearson's correlation, Fischer exact t test, and Fischer r to
z transformation were used where appropriate. RESULTS: A total of 16 patients
were enrolled. All had US data. Of the sixteen patients, two died prior to the
neurodevelopmental testing, six did not return for the neurodevelopmental
testing, and eight patients completed the neurodevelopmental testing. There were
no significant correlations between the prior to surgery and prior to discharge
US RI and neurodevelopmental outcomes. The immediate post-operative US RI
demonstrated a strong positive correlation with standardized neurodevelopmental
outcome measures. We were able to demonstrate qualitative differences using
multichannel NIRS during surgery, but experienced significant technical
difficulties implementing consistent monitoring. CONCLUSIONS: A higher resistive
index in the major cerebral blood vessels following cardiac surgery in the
neonatal period is associated with improved neurological outcomes one year after
surgery. Obtaining an ultrasound with resistive indices of the major cerebral
vessels prior to and after surgery may yield information that is predictive of
neurodevelopmental outcomes.
PMID- 28511779
TI - An Evidence-based Review of the Efficacy of Treatment Approaches for Immature
Permanent Teeth with Pulp Necrosis.
AB - INTRODUCTION: Two fundamental assumptions for teeth treated with regenerative
endodontic procedures (REPs) are (1) that the clinical outcome is comparable with
the traditional techniques of calcium hydroxide apexification and mineral
trioxide aggregate apical barrier techniques and (2) that REPs will result in
further root maturation. METHODS: A systematic review of the electronic databases
(Scopus, PubMed, and Web of Science) involved a search for studies that used
quantitative assessments of root maturation. The search terms were "dental pulp,"
"regenerative endodontic therapy," "revascularization," and "revitalization." The
identified studies were further screened for cohort studies that compared
clinical outcomes between teeth treated with REPs and apexification/apical
barrier approaches. The primary question under review was framed according to the
population, exposure, and outcome format. RESULTS: Of the 368 studies identified
by the search, 6 cohort studies used quantitative assessments of any further root
maturation after REPs, and a subset of 4 of these cohort studies assessed and
compared clinical outcomes between the different treatment approaches.
CONCLUSIONS: Immature teeth with pulp necrosis treated with REPs generally show
further root maturation although the results are variable. Clinical outcomes were
similar for both groups. Patient-based criteria such as tooth discoloration,
indications for changing the treatment option, and number of treatment
appointments are all important for discussion before electing the appropriate
treatment plan for the management of immature teeth with pulp necrosis.
PMID- 28511780
TI - Anti-Mycobacterium avium complex activity of clarithromycin, rifampin, rifabutin,
and ethambutol in combination with adenosine 5'-triphosphate.
AB - We previously reported that adenosine 5'-triphosphate (ATP) inhibited the growth
of various bacteria, including mycobacteria, Staphylococcus, and Pseudomonas,
without damaging bacterial surface structures. Notably, ATP's antibacterial
activity was found to be attributable to its iron-chelating ability. ATP
exhibited combined effects with some antimicrobials against Mycobacterium
intracellulare and methicillin-resistant S. aureus, suggesting its usefulness as
an adjunctive drug in the chemotherapy against certain intractable infections. In
this study, we examined detailed profiles of the anti-Mycobacterium avium complex
(MAC) activity of some antimicrobial agents, including clarithromycin (CLA),
rifampin (RIF), rifabutin (RBT), and ethambutol (EMB), in combination with ATP.
It was found that the anti-MAC activity of CLA+RIF, CLA+RBT, and CLA+EMB was
markedly potentiated in a strain-dependent manner. In this case, the onset of the
regrowth of antimicrobial agent-treated mycobacteria during cultivation was
significantly delayed in the presence of ATP, indicating the usefulness of ATP as
an adjunctive drug in chemotherapy against MAC infections.
PMID- 28511781
TI - Correlation of right atrial enlargement on ECG to right atrial volume by
echocardiography in patients with pulmonary hypertension.
AB - Previous attempts to validate ECG criteria for right atrial (RA) enlargement
(RAE) have been limited by sample sizes and lack of accepted standards for
measuring RA size. New guidelines have recommended that RA volume (RAV) be used
to determine RA size. Since these guidelines were released, no studies have been
published that correlate RAE by ECG to RAV using the new standards. We aimed to
validate previously proposed ECG criteria for RAE, commonly called P pulmonale,
and to establish whether a correlation exists between P wave amplitudes and RAV
as determined by echocardiogram in patients from the pulmonary hypertension (PHT)
clinic. We identified patients from the PHT clinic that had an echocardiogram and
ECG done at most 30days apart. We defined increased P wave amplitude as >=2mm in
lead II and >=1mm in lead V1. The RA was determined to be enlarged if the RAV
index (RAVI) was >=39mL/m2 for men and >=33mL/m2 for women. Patients were
stratified into four groups: those with P II>=2mm, those with P V1>=1mm, those
that met both criteria, and those that met neither. Right atrial volumes were
then compared. Sixty-three patients were included in the study (7 men, 56 women).
Three men and 36 women had an ECG that met criteria for P pulmonale. Five men and
28 women had an enlarged RA on echocardiogram. Sixty-nine percent of ECGs that
met criteria for RAE were associated with increased RAV by echocardiogram. The
specificity of each of the ECG criteria for P pulmonale at detecting RAE was 100%
for men. The criterion with the highest specificity among women was P II>=2mm AND
P V1>=1mm (94%). The least specific criterion for women was P II>=2mm (70%). The
sensitivity of each criterion was much lower. The most sensitive criteria for men
and women were P V1>=1mm (66.6%) and P II>=2mm (48%), respectively. The
correlation of P wave amplitude in leads II and V1 and RAVI was not statistically
significant for any of the ECG criteria for P pulmonale. In patients from the PHT
clinic, the specificity of P pulmonale for detecting RAE is high, but the
sensitivity is relatively low. These results suggest that in PHT, P pulmonale can
be used to confirm that the RA is enlarged, but it is not a reliable test for
diagnosing RAE.
PMID- 28511782
TI - Prevalence of early repolarization pattern in patients with lone atrial
fibrillation.
AB - BACKGROUND: The objective of this study was to test the association of early
repolarization pattern (ER) with lone atrial fibrillation (AF). METHODS:
Electrocardiograms (ECGs) were analyzed in blinded fashion in a case-control
study of 182 patients with lone AF and 182 controls without AF. RESULTS: Patients
with lone AF and controls had similar frequencies of ER pattern (15% vs. 19%,
p=0.40). In patients <50years of age, there was also no difference in the
percentage of patients with ER in the AF and control groups (17% vs. 19%,
p=0.60). ER pattern was more common in patients with ECG voltage criteria of left
ventricular hypertrophy (LVH), with ER present in 57% of patients with elevated
Sokolow-Lyon voltage compared to 14% of those without (p<0.0001). CONCLUSIONS: No
association could be identified between the ER pattern and lone AF in young and
middle-aged patients. In this age group, ER is substantially more common in
patients with elevated Sokolow-Lyon voltage criteria.
PMID- 28511784
TI - Editor in Chief's response: Women's talents.
PMID- 28511783
TI - Is elaboration of affective content sufficient to attenuate emotional responses
during reappraisal procedures?
AB - Reappraisal is an emotion regulation strategy which involves changing the
interpretation of emotional stimuli. It decreases measures of negative affect
together with markers of emotional processing, including late positive potential
(LPP). Affective responses can also be attenuated by various cognitive tasks. As
reappraisal tasks require cognitive effort to elaborate emotional stimuli, it is
possible that the observed reduction of the LPP amplitude during reinterpretation
is, at least partly, caused by an unspecific cognitive activity. The aim of the
study was to examine, whether mental activity other than cognitive change carried
out directly on affective stimuli can be a factor that significantly modifies the
intensity of the emotional responses. Three groups took part in an experiment
with standardized emotional pictures: a reappraisal group (trained in
reinterpretation), a retro group (trained in cognitive elaboration of emotional
stimuli other than cognitive change), and a control group (passive viewing). The
early LPP potential showed a main effect of group with the highest amplitude in
the control group and the lowest amplitude in the reappraisal group. The retro
group revealed no significant differences comparing with the other two groups.
The late LPP was indistinguishable in the reappraisal and retro groups, which
showed an equal decrease in its amplitude compared to the control group in the
case of negative stimuli. Conversely, behavioral ratings collected in a separate
group of subjects showed a decrease in negative feelings in the reappraisal group
only. We conclude that the LPP component during reappraisal is under additive
influence from the cognitive change itself and from unspecific cognitive
activity; however, both of them differ in regard to their temporal
characteristics.
PMID- 28511785
TI - Reply to "Letter to the Editor" by Moran et al. "Comment on 'Potentized estrogen
in homeopathic treatment of endometriosis associated pelvic pain: A 24-week,
randomized, double-blind, placebo-controlled study'".
PMID- 28511786
TI - Corrigendum to "The neuroprotective compound P7C3-A20 promotes neurogenesis and
improves cognitive function after stroke" [Exp. Neurol. 290 (2017) 63-73].
PMID- 28511788
TI - Porous structure of ion exchange membranes investigated by various techniques.
AB - A comparative review of various techniques is provided: mercury intrusion
porosimetry, nitrogen sorption porosimetry, differential scanning calorimetry
(DSC)-based thermoporosimetry, and standard contact porosimetry (SCP), which
allows determining pore volume distribution versus pore radius/water binding
energy in ion-exchange membranes (IEMs). IEMs in the swollen state have a labile
structure involving micro-, meso- and macropores, whose size is a function of the
external water vapor pressure. For such materials, the most appropriate methods
for quantifying their porosity are DSC and SCP. Especially significant
information is given by the SCP method allowing measuring porosimetric curves in
a very large pore size range from 1 to 105nm. Experimental results of water
distribution in homogeneous and heterogeneous commercial and modified IEMs are
presented. The effect of various factors on water distribution is reviewed, i.e.
nature of polymeric matrix and functional groups, method for membrane
preparation, membrane ageing. A special attention is given to the effect of
membrane modification by embedding nanoparticles in their structure. The
porosimetric curves are considered along with the results of electrochemical
characterization involving the measurements of membrane conductivity, as well as
diffusion and electroosmotic permeability. It is shown that addition of
nanoparticles may lead to either increase or decrease of water content in IEMs,
different ranges of pore size being affected. Hybrid membranes modified with
hydrated zirconium dioxide exhibit much higher permselectivity in comparison with
the pristine membranes. The diversity of the responses of membrane properties to
their modification allows for formation of membranes suitable for fuel cells,
electrodialysis or other applications.
PMID- 28511787
TI - Comparative and cost-effectiveness research: Competencies, opportunities, and
training for nurse scientists.
AB - BACKGROUND: Comparative and cost-effectiveness research develops knowledge on the
everyday effectiveness and value of treatments and care delivery models. PURPOSE:
To describe comparative and cost-effectiveness research; identify needed
competencies for this research; identify federal funding; and describe current
training opportunities. METHODS: Published recommended competencies were
reviewed. Current federal funding and training opportunities were identified. A
federally funded training program and other training opportunities are described.
DISCUSSION: Fourteen core competencies were identified that have both analytic
and theoretical foci from nursing and other fields. There are multiple sources of
federal funding for research and training. Interdisciplinary training is needed.
CONCLUSION: Comparative and cost-effectiveness research has the opportunity to
transform health care delivery and improve the outcomes of patients. Nurses, as
clinicians and scientists, are in a unique position to contribute to this
important research. We encourage nurses to seek the needed interdisciplinary
research training to participate in this important endeavor. We also encourage
educators to use the competencies and processes identified in current training
programs to help shape their doctoral programs.
PMID- 28511789
TI - Salicylic acid mediated growth, physiological and proteomic responses in two
wheat varieties under drought stress.
AB - : Salicylic acid (SA) induced drought tolerance can be a key trait for increasing
and stabilizing wheat production. These SA induced traits were studied in two
Triticum aestivum L. varieties; drought tolerant, Kundan and drought sensitive,
Lok1 under two different water deficit regimes: and rehydration at vegetative and
flowering stages. SA alleviated the negative effects of water stress on
photosynthesis more in Kundan. SA induced defense responses against drought by
increasing antioxidative enzymes and osmolytes (proline and total soluble
sugars). Differential proteomics revealed major role of carbon metabolism and
signal transduction in enhancing drought tolerance in Kundan which was shifted
towards defense, energy production and protection in Lok1. Thioredoxins played
important role between SA and redox signaling in activating defense responses. SA
showed substantial impact on physiology and carbon assimilation in tolerant
variety for better growth under drought. Lok1 exhibited SA induced drought
tolerance through enhanced defense system and energy metabolism. Plants after
rehydration showed complete recovery of physiological functions under SA
treatment. SA mediated constitutive defense against water stress did not
compromise yield. These results suggest that exogenously applied SA under drought
stress confer growth promoting and stress priming effects on wheat plants thus
alleviating yield limitation. BIOLOGICAL SIGNIFICANCE: Studies have shown
morphological, physiological and biochemical aspects associated with the SA
mediated drought tolerance in wheat while understanding of molecular mechanism is
limited. Herein, proteomics approach has identified significantly changed
proteins and their potential relevance to SA mediated drought stress responses in
drought tolerant and sensitive wheat varieties. SA regulates wide range of
processes such as photosynthesis, carbon assimilation, protein metabolism, amino
acid and energy metabolism, redox homeostasis and signal transduction under
drought. Proteome response to SA during vegetative and reproductive growth gave
an insight on mechanism related water stress acclimation for growth and
development to attain potential yield under drought. The knowledge gained can be
potentially applied to provide fundamental basis for new strategies aiming
towards improved crop drought tolerance and productivity.
PMID- 28511790
TI - The use of front-back arrays by young children to code locations.
AB - Research suggests that during the first 2years of life, children use an
egocentric reference system and an extrinsic reference frame, the latter being
one allocentric reference system, to encode locations. However, little is known
about children's use of an object's intrinsic structure, another allocentric
reference system. The current study focused on the role of the front-back
relationship, one of the simplest intrinsic reference frames, in children's
location encoding. Children (3- to 5-year-olds) participated in a hide-and-find
game with one of three different intrinsic front-back array conditions: a facet
induced front-back array, a motion-induced front-back array, or no array. The
results showed that whereas the ability to use a facet-induced front-back array
began by 3years of age, children used a motion-induced front-back array to encode
locations at 4years of age. These results provide evidence that the developmental
trajectories of using an intrinsic reference frame to encode locations vary and
depend on the specific spatial array involved.
PMID- 28511791
TI - [Usefulness of the budget and the balanced scorecard in managing Primary Care
Centres. Impact on staff motivation].
AB - OBJECTIVE: To analyse the utility perceived by managers of centers of primary
care about management tools (budget and balanced scorecard), together their
impact on human resources motivation. DESIGN: Qualitative study (case study)
based on grounded theory performed between January and June 2014. LOCATION: Units
of Clinical Management of Primary Health (UGCAP) in Metropolitan Health Area of
Seville, Spain. PARTICIPANTS: UGCAP managers and Health Area (CEO) managers.
METHOD: Data were collected through 8 semi-structured interviews using non
probabilistic intentional sampling with representation and sufficiency criteria
of discourse. Interviews were recorded, literally transcripted and analysis
through in-vivo codes. RESULTS: Both tools are fully implemented but differently
used in primary care centers. Budget is perceived as a coercive management tool,
which has been imposed for cost saving; however, it is scarcely adequate for day
by-day management. While balanced scorecard is a more flexible tool that allows
identifying financial and welfare problems, budgeting limits heavily reduce the
possibility of implementing adequate solutions. The policy of incentives is not
adequate either, leading on de-motivation. CONCLUSIONS: This study shows that
budgeting restrictions have led to a significant reduction in autonomy of Spanish
Primary Care centers. Management decision making is much centralised, also
focused on cost saving over quality of healthcare. As a result, two needs emerge
for the future: increasing centers' autonomy and improving staff commitment
through training and professional development programs.
PMID- 28511792
TI - Mechanisms of hemispheric lateralization: A replication study.
AB - It has been shown, using functional magnetic resonance imaging (fMRI), that
hemispheric lateralization of brain activity depends on the requirements of the
cognitive task performed during the processing of a sensory stimulus rather than
on the intrinsic characteristics of that stimulus [Stephan et al., 2003, Science
301 (5631): 384-6]. Task-dependent increase in the coupling of the anterior
cingulate cortex (ACC), a region involved in cognitive control, and brain areas
in the left prefrontal and right parietal cortex, respectively, regions involved
in task execution, was proposed as the mechanism underlying this task-dependency
of hemispheric lateralization. The aim of the present study was two-fold: First,
we aimed for a conceptual replication of these findings in an independent sample
of subjects. Second, we investigated the test-retest reliability of the imaging
paradigm to assess whether the task can be used to capture reliable measures of
inter-individual differences in hemispheric lateralization. We were able to
confirm previous findings showing that hemispheric lateralization depends on the
nature of the cognitive task rather than on the nature of the processed stimuli.
The task-related brain activation patterns were highly reliable across sessions
(as indicated by intra-class correlation coefficients - ICCs, >=.51). We could,
however, not replicate previous results proposing task-dependent changes in the
coupling between ACC and brain regions for task execution as the mechanism
underlying hemispheric lateralization. This re-opens the question which
mechanisms could determine the task-dependent functional asymmetries that were
observed previously and replicated in this study.
PMID- 28511793
TI - Two sources of dopamine for the hippocampus.
AB - Dopaminergic signalling is established as playing an important role in novelty
related modulation of hippocampal memory. Two recent studies have identified the
noradrenergic fibres originating in the locus coeruleus as an additional source
of neurotransmitter acting on dopaminergic receptors in the hippocampus.
PMID- 28511794
TI - Application of end-tidal carbon dioxide monitoring via distal gas samples in
ventilated neonates.
AB - BACKGROUND: Previous research has suggested correlations between the end-tidal
partial pressure of carbon dioxide (PETCO2) and the partial pressure of arterial
carbon dioxide (PaCO2) in mechanically ventilated patients, but both the
relationship between PETCO2 and PaCO2 and whether PETCO2 accurately reflects
PaCO2 in neonates and infants are still controversial. This study evaluated
remote sampling of PETCO2 via an epidural catheter within an endotracheal tube to
determine the procedure's clinical safety and efficacy in the perioperative
management of neonates. METHODS: Abdominal surgery was performed under general
anesthesia in 86 full-term newborns (age 1-30 days, weight 2.55-4.0 kg, American
Society of Anesthesiologists class I or II). The infants were divided into 2
groups (n = 43 each), and carbon dioxide (CO2) gas samples were collected either
from the conventional position (the proximal end) or a modified position (the
distal end) of the epidural catheter. RESULTS: The PETCO2 measured with the new
method was significantly higher than that measured with the traditional method,
and the difference between PETCO2 and PaCO2 was also reduced. The accuracy of
PETCO2 measured increased from 78.7% to 91.5% when the modified sampling method
was used. The moderate correlation between PETCO2 and PaCO2 by traditional
measurement was 0.596, which significantly increased to 0.960 in the modified
sampling group. Thus, the PETCO2 value was closer to that of PaCO2. CONCLUSION:
PETCO2 detected via modified carbon dioxide monitoring had a better accuracy and
correlation with PaCO2 in neonates.
PMID- 28511795
TI - miR-142-5p regulates tumor cell PD-L1 expression and enhances anti-tumor
immunity.
AB - Cancer immunotherapy has many great achievements in recent years. One of the most
promising cancer immunotherapies is PD-1/PD-L1 pathway blockade. miRNAs
(MicroRNAs) belongs to small noncoding RNA and can regulate gene expression by
binding to the 3'UTR. Many miRNAs can inhibit cancer growth by regulating the PD
L1 expression in cancer cells. Herein, we firstly found that PD-L1 could be the
target of miR-142-5p by using bioinformatics methods, then we conduct luciferase
activity assay, RT-PCR and western blot experiments to demonstrate that miR-142
5p can regulate PD-L1 expression by binding to its 3'UTR. And in vivo experiments
certified that miR-142-5p overexpression can inhibit pancreatic cancer growth.
Flow cytometry and RT-PCR experiment demonstrated that miR-142-5p overexpression
on tumor cells inhibits the expression of PD-L1 on tumor cells which result in
the increase of CD4+ T lymphocytes and CD8+ T lymphocytes, the decrease of PD-1+
T lymphocytes and increase of IFN-gamma and TNF-alpha. So, miR-142-5p
overexpression can enhance anti-tumor immunity by blocking PD-L1/PD-1 pathway.
Our results identify a novel mechanism by which PD-L1 is regulated by miR-142-5p
and overexpression of miR-142-5p could enhance the anti-tumor immunity.
PMID- 28511796
TI - Attenuation of deregulated miR-369-3p expression sensitizes non-small cell lung
cancer cells to cisplatin via modulation of the nucleotide sugar transporter
SLC35F5.
AB - Deregulation of the microRNAs (miRNAs), a cluster of important
posttranscriptional regulators, has been frequently associated with lung cancer
(LCa). However, the emerging mechanism for how miRNAs is linked causally in the
development of LCa chemoresistance is poorly understood. Herein, we established
for the time the up-regulation of miR-369-3p in cisplatin (DDP)-resistant
nonsmall cell lung cancer (NSCLC) tissues and cells. Its deregulation was found
to be correlated to the magnitude of malignancy in well-characterized LCa cells.
Functionally, inhibition of miR-369-3p sensitized LCa cells to DDP and suppressed
the invasive capability in the presence of DDP treatment, whereas miR-369-3p
overexpression promoted DDP resistance and thereby enhanced LCa cells
invasiveness. Mechanistically, bioinformatics coupled with luciferase and gain-of
function, loss-of-function assays revealed that miR-369-3p may regulate DDP
chemoresistance by directly targeting the 3' untranslated region (UTR) of human
solute carrier 35F5 (SLC35F5), as application of miR-369-3p inhibitors or
reintroduction of epigenetically silenced SLC35F5 both individually sensitized
LCa cells to DDP, but combined treatment with miR-369-3p inhibitors and SLC35F5
overexpression failed to sensitized LCa cells further to DDP-elicited cell death.
Our results provide evidence that the oncomiR effect of miR-369-3p may be
mediated through disrupting the nucleotide sugar transportation and that SLC35F5
is a key effector of this chemoresistance-promoting activity.
PMID- 28511797
TI - Deficiency of liver-X-receptor-alpha reduces glucose uptake and worsens post
myocardial infarction remodeling.
AB - Liver X receptor alpha (LXRalpha) is an endogenous protective receptor against
ischemic heart diseases. However, whether LXRalpha regulated glucose metabolism
in ischemic heart diseases has not been investigated. In this study we
investigated the involvement of LXRalpha on glucose metabolism in cardiac
remodeling after myocardial infarction (MI). MI was induced in mice by permanent
ligation of the left anterior descending coronary artery (LCA). Genetic LXRalpha
deletion significantly worsened cardiac remodeling and impaired cardiac function
at 4 weeks after MI. Cardiac 18F-fluorodeoxyglucose (FDG) uptake by positron
emission tomography (PET) demonstrated that the FDG standardized uptake value
(SUV) was significantly lower in LXRalpha-/- mice as compared to WT mice.
Mechanistically, GLUT1/4 and AMPK phosphorylation were significantly
downregulated while CD36 expression was markedly upregulated in LXRalpha-/- mice.
This study demonstrated that deficiency of LXRalpha decreased glucose uptake
after MI, resulting in a metabolic shift that suppressed glucose metabolism,
which was in association with adverse cardiac remodeling.
PMID- 28511798
TI - Induction of copper and iron in acute cold-stimulated brown adipose tissues.
AB - Copper (Cu) and iron (Fe), the enzymatic cofactors required for various
biochemical processes, have been recently linked to lipid metabolism. Adipose
tissues play central roles in energy balance and whether copper and iron
homeostasis is involved in cold-stimulated energy metabolism remains unknown. In
this study, the Cu and Fe contents in interscapular brown adipose tissue (BAT)
and subcutaneous white adipose tissue (subWAT) from mice at different
developmental stages were measured. Our results revealed the dynamic changes of
Cu and Fe levels during development, suggesting their potential roles in energy
homeostasis. Furthermore, the significantly increased Cu and Fe contents and the
markedly up-regulated CTR1 and ATP7A expression in acute cold-stimulated BAT
indicates the involvement of both Cu and Fe in the BAT-mediated thermogenesis.
Comparably, no change in the Cu and Fe levels in cold-stimulated subWAT was
observed at the indicated time points, suggesting that both metals are not
involved in the cellular process of cold-induced WAT browning. Taken together,
these data demonstrate the induction of Cu and Fe in acute cold-stimulated BAT
activation, thus providing the direct evidences of the involvement of copper and
iron homeostasis in BAT-mediated non-shivering energy metabolism.
PMID- 28511799
TI - Towards a Grand Unified Theory of sports performance: A response to the
commentaries.
PMID- 28511800
TI - Epidemiologic pattern of paediatric supracondylar fractures of humerus in a
teaching hospital of rural India: A prospective study of 263 cases.
AB - PURPOSE: This prospective study aimed to investigate the epidemiologic parameters
of supracondylar humeral fractures in children admitted to a teaching institution
of a developing country primarily catering to rural population, to find any
preventable cause of such injuries. METHODS: All suspected cases of supracondylar
humeral fracture reporting to emergency or outpatients department were analysed
for various epidemiologic parameters including age, sex, laterality, time of
presentation, associated injuries, neurovascular complications and classification
over a period of four years. RESULTS: We analysed a total of 263 patients and
most of the fractures were seen in 5-8-year age group with a mean of 7.9 years. A
total of 157 cases were males and non-dominant extremity was involved in 65% of
fractures in our series. Fall on outstretched hand was the predominant cause of
injury and fall from rooftop was the predominant mode. In all patients, 36.12%
reported to our hospital 1 week after injury, 39.92% presented to hospital within
48 h after trauma and the remaining 23.95% presented 48 h to 1 week after trauma.
None had a bilateral injury. Gartland type 3 fractures constituted 54.37% of
patients, followed by type 1 (23.95%) and type 2 (21.67%). CONCLUSION: Almost one
fourth of supracondylar humeral fractures in children can be prevented by
installing railing of rooftops and stairs. It is necessary to educate people on
hazards of treatment by traditional bonesetters. Moreover, the children with
supracondylar humeral fractures should be screened for associated injuries.
PMID- 28511801
TI - Intergenerational differences in the effects of transcatheter closure of atrial
septal defects on cardiac function.
AB - BACKGROUND: Little is known regarding intergenerational differences in the
effects of atrial sepal defect (ASD) closure on the left heart. We therefore
analyzed age-related serial changes in the left heart following ASD closure.
METHODS: We studied 50 patients with an isolated ASD who underwent successful
transcatheter closure using Amplatzer septal occluders (St. Jude Medical, Little
Canada, MN, USA) between June 2007 and June 2013. Patients were divided into
three age groups: young patients aged <=17 years; middle-aged patients aged 18-50
years; and older patients aged >50 years. Multi-modal echocardiographic studies
with different views were performed before and at 1 day, 1-3 months, and 6-12
months after ASD closure. Echocardiographic variables were compared among the
groups at different time points after closure. RESULTS: Left ventricular end
diastolic and end-systolic volume indices (EDVI and ESVI) in the older group were
significantly smaller than those in the other groups before closure. EDVI and
ESVI increased with time after closure in all groups with stable ejection
fractions. However, EDVI and ESVI remained significantly smaller in the older
group compared with the other groups. There was a significant interaction among
the age groups only in terms of left atrial volume index (LAVI). LAVI increased
significantly with time in the older group, but did not change in the other
groups. CONCLUSION: Although the left ventricle enlarged with time after ASD
closure in all age groups, left ventricular size in older patients never reached
that in younger patients. In addition to this inadequate enlargement of the left
ventricle, diastolic dysfunction might also result in late left atrial
enlargement in older patients following ASD closure.
PMID- 28511802
TI - [A continuous series of 27 adult patients treated for L5-S1 isthmic
spondylolisthesis by combined approach: Clinical and radiological outcomes at 1
year follow-up].
AB - Through this single-center consecutive prospective study, we evaluated the
results of a combined approach for L5-S1 isthmic spondylolisthesis, using a
polyetheretherketone (PEEK) interbody lordotic cage during anterior approach and
pedicle screw-based posterior fixation. Between 2010 and 2014, 27 adult patients
were treated for L5-S1 isthmic spondylolisthesis (high and low grades) by a
combined approach with a minimum follow-up of one year. Clinical outcome was
assessed before surgical treatment and at four months and one year after surgery
by: VAS, Oswestry Index (ODI) and Rolland-Morris scores. Two observers evaluated
the following radiological parameters: pelvic incidence, pelvic tilt, lumbar
lordosis, segmental lordosis L5-S1, anterior and posterior disc height, spinal
vertical axis (SVA), SVA/sacro-femoral distance (SFD) ratio. Fusion was evaluated
on the CT scan at one-year follow-up. Blood loss, surgery time and complications
were also collected. The mean age was 47.7 years (+/-16.9). The VAS, ODI and
Rolland-Morris scores were significantly improved postoperatively, decreased from
7.5 (+/-1.45); 48 (+/-19.25); 15.3 (+/-4.67) before the surgery to 3.8 (+/-2.55);
28.7 (+/-19.58) and 7.76 (+/-7.21) respectively at one year after the surgery
(P=0.05). The mean follow-up was 3.3 years. Mean surgery time was 193.7min (+/
37). Fusion was obtained in 100% of cases. Segmental lordosis L5-S1, pelvic tilt,
slippage, anterior and posterior L5-S1 disc height were significantly improved
postoperatively, they passed from 20.1; 22.6; 35.3%; 26.4%; 17.9% to 29.5; 20.6;
20.3%; 64.4%; 36.3% respectively. Combined surgical procedure meets the required
goals of surgery in the treatment of adults L5-S1 isthmic spondylolisthesis.
PMID- 28511803
TI - Group members' questions shape participation in health counselling and health
education.
AB - OBJECTIVE: This study examines how group members' questions shape member
participation in health counselling and health education groups. METHODS: The
study applies conversation analytic principles as a method. The data consist of
video-recorded health education lessons in secondary school and health
counselling sessions for adults with a high risk of Type 2 diabetes. RESULTS:
Group members' questions accomplish a temporary change in participatory roles.
They are used to 1) request counselling, 2) do counselling or 3) challenge
previous talk. They are usually treated as relevant and legitimate actions by the
participants, but are occasionally interpreted as transitions outside the current
action or topic. CONCLUSION: Group members' questions result in a shift from
leader-driven to member-driven discussion. Thus they constitute a pivot point for
detecting changes in participation in group interventions. PRACTICE IMPLICATIONS:
Observing the occurrence of group members' questions helps group leaders to
adjust their own actions accordingly and thus facilitate or guide group
participation. Comparison of the type and frequency of members' questions is a
way to detect different trajectories for delivering group interventions and can
thus be used to develop methods for process evaluation of interventions.
PMID- 28511805
TI - Evidence for resection of sarcoma pulmonary metastases: More, but better?
PMID- 28511804
TI - How long do I have? Observational study on communication about life expectancy
with advanced cancer patients.
AB - OBJECTIVE: To examine how communication about life expectancy is initiated in
consultations about palliative chemotherapy, and what prognostic information is
presented. METHODS: Patients with advanced cancer (n=41) with a median life
expectancy <1year and oncologists (n=6) and oncologists-in-training (n=7) meeting
with them in consultations (n=62) to discuss palliative chemotherapy were
included. Verbatim transcripts of audio-recorded consultations were analyzed
using MAXqda10. RESULTS: Life expectancy was addressed in 19 of 62 of the
consultations. In all cases, patients took the initiative, most often through
direct questions. Estimates were provided in 12 consultations in various formats:
the likelihood of experiencing a significant event, point estimates or general
time scales of "months to years", often with an emphasis on the "years". The
indeterminacy of estimates was consistently stressed. Also their potential
inadequacy was regularly addressed, often by describing beneficial prognostic
predictors for the specific patient. Oncologists did not address the reliability
or precision of estimates. CONCLUSION: Oncologists did not initiate talk about
life expectancy, they used different formats, emphasized the positive and
stressed unpredictability, yet not ambiguity of estimates. PRACTICE IMPLICATIONS:
Prognostic communication should be part of the medical curriculum. Further
research should address the effect of different formats of information provision.
PMID- 28511806
TI - STEMI could be the primary presentation of acute aortic dissection.
AB - BACKGROUND: Stanford type A aortic dissection (TAAD) may lead to coronary artery
occlusion and malfunction. However, TAAD manifesting as acute ST-segment
elevation myocardial infarction (STEMI) has not been studied. In the present
study, we reported 8 TAAD cases with STEMI as the primary presentation, and
analyzed their clinical characteristics and outcome. METHODS: The records were
reviewed for patients admitted to the large comprehensive university hospital for
PCI due to STEMI from January 1, 2002 to January 1, 2017. RESULTS: The incidence
of STEMI secondary to TAAD in our center was 0.51% (8/1,576). A total of 5
patients underwent urgent coronary angiography (CAG) without awareness of TAAD.
Compression at the ostium of right coronary artery (RCA) was found in 2 patients,
dissected flap of RCA in 1 patient, and heterogeneous filling and false lumen in
RCA in 1 patient. Three of these 5 patients received surgery and survived. One
patient accepted urgent RCA stenting because of cardiogenic shock and died after
refusal of surgical therapy and failure of medical treatment. Another 2 patients
received thrombolytic therapy died prior to CAG. Thus, the total in-hospital
mortality was 37.5% (3/8). CONCLUSIONS: TAAD presenting as STEMI was a rare
condition that predominantly involved RCA. A quick and correct clinical diagnosis
of STEMI caused by TAAD prior to invasive procedure would be important. Urgent
CAG without awareness of TAAD could provide important information for a timely
diagnosis. High level of suspicion and awareness is the key to establishing the
diagnosis and achieving optimal clinical outcome.
PMID- 28511807
TI - Does the novel lateral trauma position cause more motion in an unstable cervical
spine injury than the logroll maneuver?
AB - OBJECTIVE: Prehospital personnel who lack advanced airway management training
must rely on basic techniques when transporting unconscious trauma patients. The
supine position is associated with a loss of airway patency when compared to
lateral recumbent positions. Thus, an inherent conflict exists between securing
an open airway using the recovery position and maintaining spinal immobilization
in the supine position. The lateral trauma position is a novel technique that
aims to combine airway management with spinal precautions. The objective of this
study was to compare the spinal motion allowed by the novel lateral trauma
position and the well-established log-roll maneuver. METHODS: Using a full-body
cadaver model with an induced globally unstable cervical spine (C5-C6) lesion, we
investigated the mean range of motion (ROM) produced at the site of the injury in
six dimensions by performing the two maneuvers using an electromagnetic tracking
device. RESULTS: Compared to the log-roll maneuver, the lateral trauma position
caused similar mean ROM in five of the six dimensions. Only medial/lateral linear
motion was significantly greater in the lateral trauma position (1.4mm (95%
confidence interval [CI] 0.4, 2.4mm)). CONCLUSIONS: In this cadaver study, the
novel lateral trauma position and the well-established log-roll maneuver resulted
in comparable amounts of motion in an unstable cervical spine injury model. We
suggest that the lateral trauma position may be considered for unconscious non
intubated trauma patients.
PMID- 28511810
TI - The Case for an Epilepsy and Clinical Neurophysiology Match.
PMID- 28511808
TI - Astaxanthin from shrimp efficiently modulates oxidative stress and allied cell
death progression in MCF-7 cells treated synergistically with beta-carotene and
lutein from greens.
AB - This study investigated the synergistic efficacy of keto-carotenoid astaxanthin
(AST, from shrimp) plus hydrocarbon (beta-carotene, BC) and hydroxyl (lutein, L)
carotenoids (from greens) on molecular events in MCF-7 cells. MCF-7 cells were
treated with either of carotenoid (20 MUM, AST or BC or L) separately or the
mixture of them (an equimolar concentration of carotenoids mixture, CM) or
saponified carotenoid extract from shrimp (SSCE) for 48 h and analyzed cellular
uptake, cytotoxicity, and apoptosis. The IC50 and combination-index values of AST
co-treatment with a lower concentration of BC and L (5 MUM) exhibited enhanced
cytotoxicity and oxidative stress as compared with individual carotenoids or
SSCE. Further, higher cellular uptake/accumulation of AST along with BC and L
found to synergistically induce apoptosis through modulation of cyclin D1, p53,
Bax and Bcl-2 expressions by arresting cell cycle at G0/G1 phase. Further, CM or
SSCE treatments are unlikely to affect proliferation of normal breast epithelial
cells (MCF-10A). The results of selective killing of MCF-7 cells demonstrated a
greater insight on the synergistic effect of shrimp AST plus BC and L. It is
concluded that consumption of shrimp along with green leafy vegetables helps in
combating cancer chemoprevention.
PMID- 28511811
TI - Autoimmune Voltage-Gated Potassium Channelopathy Presenting With Catecholamine
Excess.
AB - BACKGROUND: Autoimmune voltage-gated potassium channelopathies have been
associated with a range of neurological presenting symptoms, including central,
peripheral, and autonomic dysfunction. PATIENT DESCRIPTION: We describe a 12-year
old boy who presented with nine months of pain, anxiety, and 30-pound weight
loss. He was admitted for failure to thrive, then noted to be persistently
hypertensive and tachycardic. Plasma metanephrines and urine metanephrines and
catecholamines were elevated. Extensive investigation for causes of elevated
catecholamines, such as hyperthyroidism or catecholamine-secreting tumor, was
negative. A paraneoplastic panel was positive for voltage-gated potassium channel
antibodies. Treatment with intravenous immunoglobulin and pulse
methylprednisolone led to complete resolution of symptoms, weight gain, and
normalization of vital signs and plasma metanephrines. CONCLUSION: Voltage-gated
potassium channel antibodies should be considered as part of the differential in
patients presenting with elevated metanephrine and catecholamine secretion.
PMID- 28511809
TI - Characterisation of the selective binding of antibiotics vancomycin and
teicoplanin by the VanS receptor regulating type A vancomycin resistance in the
enterococci.
AB - A-type resistance towards "last-line" glycopeptide antibiotic vancomycin in the
leading hospital acquired infectious agent, the enterococci, is the most common
in the UK. Resistance is regulated by the VanRASA two-component system,
comprising the histidine sensor kinase VanSA and the partner response regulator
VanRA. The nature of the activating ligand for VanSA has not been identified,
therefore this work sought to identify and characterise ligand(s) for VanSA. In
vitro approaches were used to screen the structural and activity effects of a
range of potential ligands with purified VanSA protein. Of the screened ligands
(glycopeptide antibiotics vancomycin and teicoplanin, and peptidoglycan
components N-acetylmuramic acid, D-Ala-D-Ala and Ala-D-y-Glu-Lys-D-Ala-D-Ala)
only glycopeptide antibiotics vancomycin and teicoplanin were found to bind VanSA
with different affinities (vancomycin 70MUM; teicoplanin 30 and 170MUM), and were
proposed to bind via exposed aromatic residues tryptophan and tyrosine.
Furthermore, binding of the antibiotics induced quicker, longer-lived
phosphorylation states for VanSA, proposing them as activators of type A
vancomycin resistance in the enterococci.
PMID- 28511812
TI - Acute Management of Symptomatic Subependymal Giant Cell Astrocytoma With
Everolimus.
AB - BACKGROUND: Subependymal giant cell astrocytomas (SEGA) are slow-growing tumors,
which can cause obstructive hydrocephalus in patients with tuberous sclerosis
complex (TSC). These tumors require routine surveillance with magnetic resonance
imaging. Current consensus guidelines recommend treatment of asymptomatic SEGAs
with an mechanistic target of rapamycin (mTOR) inhibitor because these
medications have demonstrated efficacy and safety in multiple prospective
clinical trials. For symptomatic SEGAs, standard therapy typically involves
surgical resection of the tumor to relieve mass effect and resolve hydrocephalus.
However, resection can be associated with significant perioperative morbidity and
complications. There are anecdotal reports of using mTOR inhibitors to reduce
tumor size in preparation for surgery, but prospective studies comparing sole
mTOR inhibitor therapy with surgical management have not been completed. METHODS:
Here, we present a seven-year-old boy with a large, symptomatic SEGA which was
treated acutely with everolimus. RESULTS: Everolimus treatment resulted in rapid
reduction in tumor size, symptomatic improvement, and decrease in cerebrospinal
fluid protein. CONCLUSIONS: Everolimus can effectively reduce tumor size,
decrease cerebrospinal fluid protein, and allow successful ventriculoperitoneal
shunt placement without the need for surgical resection of a symptomatic SEGA.
PMID- 28511813
TI - Conservative management of mallet injuries: A national survey of current practice
in the UK.
AB - INTRODUCTION: Mallet injuries are common and usually treated conservatively.
Various systematic reviews have found a lack of evidence regarding the best
management, and it is unclear whether this uncertainty is reflected in current UK
practice. METHODS: An online survey was developed to determine the current
practice for the conservative treatment of mallet injury among specialist hand
clinicians in the UK, including physiotherapists, occupational therapists and
surgeons. Clinician's views of study outcome selection were also explored to
improve future trials. RESULTS: In total, 336 professionals completed the survey.
Inconsistency in overall practice was observed in splint type choice, time to
discharge to GP, and assessment of adherence. Greater consistency was observed
for recommended duration of continuous immobilisation. Bony injuries were most
commonly splinted for 6 weeks (n = 228, 78%) and soft tissue injuries for either
8 weeks (n = 172, 56%) or 6 weeks (n = 119, 39%). Post-immobilisation splinting
was frequently recommended, but duration varied between 2 and 10 weeks. The
outcome rated as most important by all clinicians was patient satisfaction.
DISCUSSION: There is overall variation in the current UK conservative management
of mallet injuries, and the development of a standardised, evidence-based
protocol is required. Clinicians' opinions may be used to develop a core set of
outcome measures, which will improve standardisation and comparability of future
trials.
PMID- 28511814
TI - Evaluation of the influence of mechanical activation on physical and chemical
properties of municipal solid waste incineration sludge.
AB - Despite numerous studies concerning the application of by-products in the
construction field, municipal solid waste incineration (MSWI) residues are not
widely used as secondary building materials. In some European countries, washing
treatment to the full bottom ash (BA) fraction (0-32 mm) is applied, isolating
more contaminated particles, smaller than 0.063 mm. Therefore, a MWSI sludge is
produced, having a high moisture content, and thus a limited presence of soluble
species. In order to enhance its performance as building material, here, dry
mechanical activation is applied on MSWI sludge. Thereafter, a reactivity
comparison between reference BA and untreated and treated MSWI sludge is
provided, evaluating their behaviour in the presence of cement and their
pozzolanic activity. Moreover, the mechanical performances, as 25% substitution
of Portland cement (PC) are assessed, based on the EN 450. Mechanical activation
enhances MSWI sludge physically due to the improved particle morphology and
packing. Chemically, the hydration degree of PC is enhanced by the MSWI sludge by
~25%. The milling treatment proved to be beneficial to the residues performances
in the presence of PC, providing 32% higher strength than untreated sample.
Environmentally, the compliance with the unshaped material legislation is
successfully verified, according to the Soil Quality Decree.
PMID- 28511815
TI - Signature of the Sleeper Cell: A Biomarker of HIV Latency Revealed.
AB - HIV establishes a reservoir in latently infected T cells, and this reservoir has
long hampered curative approaches. A recent study by Descours et al. identifies
CD32a as a marker of latently infected T cells, potentially opening the way to
the development of strategies that directly target this critical HIV reservoir.
PMID- 28511817
TI - The Wait.
PMID- 28511819
TI - Psychiatric dermatology revisited.
PMID- 28511820
TI - Somatic symptom disorder in dermatology.
AB - Somatic symptom disorder (SSD) is defined by the prominence of somatic symptoms
associated with abnormal thoughts, feelings, and behaviors related to the
symptoms, resulting in significant distress and impairment. Individuals with
these disorders are more commonly encountered in primary care and other medical
settings, including dermatology practice, than in psychiatric and other mental
health settings. What defines the thoughts, feelings, and behaviors as abnormal
is that they are excessive, that is, out of proportion to other patients with
similar somatic symptoms, and that they result in significant distress and
impairment. SSD may occur with or without the presence of a diagnosable
dermatologic disorder. When a dermatologic disorder is present, SSD should be
considered when the patient is worrying too much about his or her skin, spending
too much time and energy on it, and especially if the patient complains of many
nondermatologic symptoms in addition. The differential diagnosis includes other
psychiatric disorders, including depression, anxiety disorders, delusions of
parasitosis, and body dysmorphic disorder. This paper describes SSD and its
applicability in dermatologic practice, with illustrative cases.
PMID- 28511818
TI - "How the other half live": Lay perspectives on health inequalities in an age of
austerity.
AB - This paper examines how people living in two socially contrasting areas of
Stockton on Tees, North East England experience, explain, and understand the
stark health inequalities in their town. Participants displayed opinions that
fluctuated between a variety of converging and contrasting explanations. Three
years of ethnographic observation in both areas (2014-2017) generated
explanations which initially focused closely on behavioural and individualised
factors, whilst 118 qualitative interviews subsequently revealed more nuanced
justifications, which prioritised more structural, material and psychosocial
influences. Findings indicate that inequalities in healthcare, including access,
the importance of judgemental attitudes, and perceived place stigma, would then
be offered as explanations for the stark gap in spatial inequalities in the area.
Notions of fatalism, linked to (a lack of) choice, control, and fear of the
future, were common reasons given for inequalities across all participants. We
conclude by arguing for a prioritisation of listening to, and working to
understand, the experiences of communities experiencing the brunt of health
inequalities; especially important at a time of austerity.
PMID- 28511821
TI - Somatization in the dermatology patient: Some sociocultural perspectives.
AB - Somatization in dermatology patients is a challenge to diagnose and manage.
Somatization presents as medically unexplained dermatologic symptoms, which are
commonly encountered in dermatology and psychiatry practices. These cutaneous
symptoms are often intriguing and do not fit into any particular known
dermatologic condition. Sometimes, they may evoke negative feelings in the
practicing dermatologist. The dermatologic somatic symptoms might be one way of
communicating psychologic distress in a culturally acceptable method. These
somatic symptoms may be masking another psychiatric disorder such as depression.
They could also be an adaptive response to a difficult psychosocial situation and
means of coping in a culturally meaningful way; therefore, the underlying
conflicts need to be understood and managed in the sociocultural context of the
symptoms. This chapter discusses the various unexplained physical symptoms in
dermatology patients and the need for comprehensive evaluation.
PMID- 28511822
TI - Posttraumatic stress disorder (PTSD) and the dermatology patient.
AB - Dermatologic symptoms can be associated with posttraumatic stress disorder (PTSD)
in several situations: (1) as features of some core PTSD symptoms, such as
intrusion symptoms manifesting as cutaneous sensory flashbacks, as autonomic
arousal manifesting as night sweats and idiopathic urticaria, and as dissociation
manifesting as numbness and dermatitis artefacta; (2) the cutaneous psychosomatic
effects of emotional and physical neglect and sexual abuse (eg, infantile eczema,
cutaneous self-injury, and body-focused repetitive behaviors such as
trichotillomania and skin picking disorder) and eating disorders, which can have
dermatologic effects; (3) the direct effect of physical or sexual abuse or
catastrophic life events (eg, earthquakes) on the skin; and (4) as a result of
significant alterations in hypothalamic-pituitary-adrenal and sympatho-adrenal
medullary axes, which can affect neuroendocrine and immune functions, and can
lead to exacerbations of stress-reactive inflammatory dermatoses such as
psoriasis, chronic urticaria, and atopic dermatitis. Elevated levels of
inflammatory biomarkers and impaired epidermal barrier function have been
reported in situations involving sustained psychologic stress and sleep
deprivation. Some PTSD patients show hypothalamic-pituitary-adrenal axis
hyporesponsiveness and higher circulating T lymphocytes, which can exacerbate
immune-mediated dermatologic disorders. PTSD should be considered an underlying
factor in the chronic, recurrent, or treatment-resistant stress-reactive
dermatoses and in patients with self-induced dermatoses.
PMID- 28511816
TI - Mechanisms of Immune Tolerance in Leukemia and Lymphoma.
AB - The mechanisms through which immune responses are generated against solid cancers
are well characterized and knowledge of the immune evasion pathways exploited by
these malignancies has grown considerably. However, for hematological cancers,
which develop and disseminate quite differently than solid tumors, the pathways
that regulate immune activation or tolerance are less clear. Growing evidence
suggests that, while numerous immune escape pathways are shared between
hematological and solid malignancies, several unique pathways are exploited by
leukemia and lymphoma. Below we discuss immune evasion mechanisms in leukemia and
lymphoma, highlighting key differences from solid tumors. A more complete
characterization of the mechanisms of immune tolerance in hematological
malignancies is critical to inform the development of future immunotherapeutic
approaches.
PMID- 28511823
TI - Dissociation and conversion symptoms in dermatology.
AB - Dissociation and conversion (defined as the somatic component of dissociation)
can play an important mediating role in the exacerbation of the stress-reactive
dermatoses (eg, psoriasis, idiopathic urticaria, atopic dermatitis), dermatoses
that are exacerbated by excessive scratching (eg, lichen simplex chronicus,
prurigo nodularis) and koebnerization, and the self-induced dermatoses
(dermatitis artefacta, acne excoriee, skin picking disorder, trichotillomania,
onychotillomania/onychophagia). Dissociative symptoms often coexist with
obsessive-compulsive symptoms in the more severe cases of the self-induced
dermatoses. Dissociation can play an important role in cutaneous sensory disorder
(eg, scalp dysesthesia syndrome, stomatodynia/glossodynia,
vulvodynia/scrotodynia, medically unexplained anesthesia). Dissociation typically
occurs in the context of extreme psychosocial stress and a history of severe
abuse/neglect during early life. Dissociative patients may experience a sense of
detachment from their body and present in a state of extreme self-neglect,
including denial of serious skin disorders. Amnesia is one of the core symptoms
of dissociation; therefore, patients, who self-induce their skin lesions during a
dissociative episode often deny self-inducing their lesions; it is important to
recognize that this is distinct from malingering, and the lesions are not
intentionally induced. Dissociation and conversion symptoms are typically present
in the complex dermatology patient and should be assessed using a comprehensive
biopsychosocial approach.
PMID- 28511824
TI - Psychiatric disorders and pruritus.
AB - The skin and psyche are intimately related with various skin diseases caused by
or resulting in psychiatric disturbances. Pruritus is a commonly reported symptom
in psychiatric patients, and likewise psychiatric co-morbidities, including
anxiety and depression, are frequently seen in chronic pruritus patients. Primary
psychodermatologic conditions, such as somatic symptom disorder, dermatitis
artefacta, obsessive-compulsive and related disorders (excoriation disorder and
prurigo nodularis), delusional infestation, and substance use disorder, can all
induce significant pruritus in patients, severely affecting their quality of
life. Such entities can be challenging to manage, and therefore a greater
understanding of the underlying psychopathology and evaluation of associated
psychosocial factors is necessary. In addition to proper skin hygiene and first
line pharmacotherapies such as selective serotonin reuptake inhibitors,
noradrenergic and selective serotonin antidepressants, antiepileptics, and
antipsychotics (for delusional and psychotic disorders), patients with
psychopruritic disorders should be offered psychotherapy to maximize the
therapeutic efficacy.
PMID- 28511826
TI - Use of hypnosis, meditation, and biofeedback in dermatology.
AB - Hypnosis utilizes trance to access otherwise inaccessible repressed or
unconscious memories and features of the psyche and control of physiology not
attainable in the ordinary conscious waking state. Medical uses of hypnosis in
dermatology include reducing discomfort from itching or skin pain, altering
ingrained dysfunctional habits such as scratching, promoting healing of skin
disorders, searching for psychosomatic aspects of skin disorders and alleviating
them, and reframing cognitive and emotional dysfunctional patterns related to
skin disorders. Meditation uses trance to center and balance. Medical uses of
meditation in dermatology include relaxation to promote healing of skin disorders
and refocusing with respect to the meaning and emotional negative valance of skin
disorders. Biofeedback in dermatology employs instrumentation with visual or
auditory feedback to permit conscious awareness and alteration of physiologic
phenomena such as sweating as measured by galvanic skin resistance and skin
temperature measured by temperature detecting devices, promoting relaxation and
healing. These methods and techniques permit access to and intervention in
otherwise inaccessible areas that can influence skin disorders. With proper use,
they are very safe, with minimal, if any, side effects and sometimes produce
significant results where other methods have failed.
PMID- 28511825
TI - Neuropsychiatric factors in sensitive skin.
AB - Sensitive skin is a syndrome defined by the occurrence of unpleasant sensations
(stinging, burning, pain, pruritus, and tingling sensations) in response to
stimuli that normally should not provoke such sensations. The worldwide
prevalence of sensitive skin is approximately 40%. Clinical, histologic,
biochemical, and therapeutic data show that this condition is related to changes
in epidermal nerve endings with subsequent hyperreactivity and neurogenic
inflammation; hence, sensitive skin is not a psychosomatic disorder, although
psychologic consequences are possible.
PMID- 28511827
TI - Psychosomatic aspects of vitiligo.
AB - Vitiligo is a chronic common skin disease. The asymptomatic hypopigmented
cutaneous lesions are considered by many health care professionals as a cosmetic
problem only; however, vitiligo can have a major psychosocial impact on patients'
lives. We review some of the factors responsible for this impact, such as the
general public's wrong perception of the disease, feelings and emotional
responses from patients, how stressful events can act as triggers of the disease,
stigmatization experiences suffered by the patients, the prevalence of
psychiatric morbidity, the effects on relationships and sex life, how quality of
life in adults and children is impaired, and how treatment can improve it.
PMID- 28511828
TI - Body dysmorphic disorder in the dermatology patient.
AB - Body dysmorphic disorder is primarily a psychiatric disorder, in which the
patient believes that some normal or very near normal aspect of his or her
physical appearance is distorted or ugly. Should there be a minor abnormality, it
is grossly exaggerated in the mind of the patient, causing feelings of shame and
embarrassment and leading daily to spending hours at the mirror, or any
reflecting surface, as the patient tries to conceal or remove the perceived
abnormality through the development of ritualistic behavior. Although other
organs can be involved-for example, the shape of the nose or a portion of an ear-
the skin, hair, and nails are most commonly involved, while the patient
constantly seeks reassurance about appearance from friends and family. There is a
broad spectrum of severity in body dysmorphic disorder, ranging from obsessional
worry to frank delusion, and the psychiatric comorbidities-anxiety, depression,
and personality disorder-are prominent parts of the picture. Unfortunately, the
psychiatric comorbidities and the negative impact on every aspect of the
patient's life may not be recognized by dermatologists and other non-psychiatric
physicians, so that effective treatment is often not instituted or appropriate
referrals made. This paper describes the incidence, possible etiologies, and
clinical picture of body dysmorphic disorder in dermatology patients and
discusses interpersonal approaches that may permit appropriate treatment or
referral to take place. Specific treatments and prognosis are also discussed.
PMID- 28511829
TI - Suicidal behaviors in the dermatology patient.
AB - An assessment of suicidal behaviors in the dermatology patient may be necessary
in several situations: (1) in the presence of psychiatric comorbidity (major
depressive disorder, body dysmorphic disorder, substance use disorder,
posttraumatic stress disorder), encountered in up to 30% of dermatology patients;
(2) when dermatologic symptoms ("dysmorphophobia," dermatitis artefacta)
represent psychiatric pathologic conditions; (3) when psychosocial stressors
(bereavement, interpersonal violence) increase the risk of suicidal behavior and
exacerbate stress-reactive dermatoses (psoriasis, acne); (4) in the presence of
high disease burden (chronicity, increased disease severity); (5) in instances of
significant pruritus or chronic sleep disruption; (6) in the presence of facial
lesions or facial scarring; (7) when social exclusion or feelings of alienation
arise secondary to the skin disorder; (8) with use of medications (retinoids,
biologics) for which suicidal behavior has been implicated as a possible side
effect; and (9) when treating psychiatric patients experiencing a serious
reaction to psychotropic medications (eg, Stevens-Johnson syndrome and
anticonvulsants). Suicide risk must be assessed within a demographic context
because suicide rates rise rapidly in adolescents and young adults, among whom
the prevalence of skin disorders associated with suicidal behaviors (acne,
psoriasis, atopic dermatitis) is also high, and suicide rates are increasing
among white men, who tend to be overrepresented in dermatology clinical trials.
PMID- 28511830
TI - Personality disorders and the "difficult" dermatology patient: Maximizing patient
satisfaction.
AB - Personality disorders (PDs) are stable and enduring patterns of thought, feeling,
and behavior that deviate from one's cultural norms and cause impairment in
functionality. Patients with PDs are commonly encountered in the dermatologic
setting and can be perceived by providers as "difficult." Given that PDs are
chronic, rigid, and frustrating to deal with, it is important to be skillful in
the approach to such patients, especially in the era of the value-based
reimbursement system, in which patient satisfaction is crucial for reimbursement.
This contribution discusses four PDs most commonly encountered in the dermatology
setting: Borderline, histrionic, obsessive-compulsive, and narcissistic. Although
the details regarding the approach to patients for each PD differ as discussed,
once a PD is identified, there are few key management strategies that can be
helpful in minimizing conflict and enhancing outcomes. In patients with PD, the
presenting skin complaint is often a secondary problem, as there may be an
underlying psychologic issue (somatization). Understanding the underlying
psychologic aspect of the patients' dermatologic complaints and adapting
behaviors to the patients' needs are fundamental for maximizing patient
satisfaction.
PMID- 28511831
TI - Obstructive sleep apnea and dermatologic disorders.
AB - Obstructive sleep apnea (OSA) is present in at least 2% of women and 4% of men,
and its prevalence is increasing, because a major predisposing factor for OSA is
a high body mass index. Psoriasis has the most strongly substantiated link with
OSA, where the relationship may be bidirectional. Dermatologic disorders may be
comorbid with OSA due to several factors: (i) the heightened proinflammatory
state in OSA, which can occur independent of body mass index, and may exacerbate
inflammatory dermatoses; (ii) intermittent hypoxemia may promote
neovascularization and tumor growth in certain cancers, such as melanoma; (iii)
obesity, present in majority of OSA patients, can be associated with a heightened
proinflammatory state; (iv) upper airway obstruction due to local tumors or soft
tissue swelling due to physical urticaria or angioedema; (v) acute nasal
congestion in the atopic patient with allergic rhinitis; (vi) dermatologic
disorders associated with other OSA risk factors (eg, acanthosis nigricans and
metabolic syndrome); and (vii) a high sympathetic tone (eg, in atopic dermatitis)
and resultant sleep fragmentation contributing to upper airway instability during
sleep. In many instances, the dermatology patient with OSA may have other medical
and psychiatric comorbidities that are also associated with increased OSA risk.
PMID- 28511832
TI - Impact factor: Universalism and reliability of assessment.
AB - In 1955, Eugene Garfield (1925-1917) published a paper in Science where for the
first time he advocated the necessity of introducing parameters to assess the
quality of scientific journals. Underlying this necessity was an observation of a
trend where the whole area of influence in academic publishing was dominated by a
narrow group of large interdisciplinary research journals. For this reason, along
with Irving H. Sher, they created the impact factor (IF), also called the
Garfield impact factor, journal citation rate, journal influence, and journal
impact factor. The concept of IF concerns a research discipline called
bibliometrics, which uses mathematical and statistical methods to analyze
scientific publications. Established by Garfield in 1963, the Science Citation
Index, a record of scientific publications and citations therein, contributed
directly to the increased importance of this method. Since the 1960s, the
register of scientific publications has expanded and their evaluation by the IF
has become a fundamental and universal measure of the journal's value. Contrary
to the authors' intentions in the creation of the index (IF), it is often used to
assess the quality of contributions, simultaneously assessing the authors'
achievements or academic career and academic institutions' funding possibilities.
PMID- 28511833
TI - Isotretinoin in retrospect.
PMID- 28511834
TI - An assault to the National Academies of Venezuela.
PMID- 28511836
TI - Corrigendum to "Morbidity and mortality of very low birth weight infants in
Taiwan-Changes in 15 years: A population based study" [J Formos Med Assoc 115
(2016) 1039-1045].
PMID- 28511835
TI - ADCY5-related movement disorders: Frequency, disease course and phenotypic
variability in a cohort of paediatric patients.
AB - INTRODUCTION: ADCY5 mutations have been recently identified as an important cause
of early-onset hyperkinetic movement disorders. The phenotypic spectrum
associated with mutations in this gene is expanding. However, the ADCY5
mutational frequency in cohorts of paediatric patients with hyperkinetic movement
disorders has not been evaluated. METHODS: We performed a screening of the entire
ADCY5 coding sequence in 44 unrelated subjects with genetically undiagnosed
childhood-onset hyperkinetic movement disorders, featuring chorea alone or in
combination with myoclonus and dystonia. All patients had normal CSF analysis and
brain imaging and were regularly followed-up in tertiary centers for paediatric
movement disorders. RESULTS: We identified five unrelated subjects with ADCY5
mutations (11% of the cohort). Three carried the p. R418W mutation, one the p.
R418Q and one the p. R418G mutation. Mutations arose de novo in four cases, while
one patient inherited the mutation from his similarly affected father. All
patients had delayed motor and/or language milestones with or without axial
hypotonia and showed generalized chorea and dystonia, with prominent myoclonic
jerks in one case. Episodic exacerbations of the baseline movement disorder were
observed in most cases, being the first disease manifestation in two patients.
The disease course was variable, from stability to spontaneous improvement during
adolescence. CONCLUSION: Mutations in ADCY5 are responsible for a hyperkinetic
movement disorder that can be preceded by episodic attacks before the movement
disorder becomes persistent and is frequently misdiagnosed as dyskinetic cerebral
palsy. A residual degree of neck hypotonia and a myopathy-like facial appearance
are frequently observed in patients with ADCY5 mutations.
PMID- 28511837
TI - Immunomodulatory activity of recombinant alpha-gliadin conjugated to cholera
toxin in DQ8 transgenic mice.
AB - Coeliac disease (CD) is characterized by an intestinal lesion sustained by an
abnormal mucosal T-cell response to wheat gliadin. An immunological approach that
is able to suppress this immune response is a perspective worth pursuing. Several
strategies of antigen administration have been aimed at the downregulation of
pathogenic T-cells. In particular, we previously reported a significant
suppression of the systemic cell-mediated response toward wheat gliadin in DQ8
transgenic mice receiving nasally a recombinant alpha-gliadin. To gain further
insight about the cellular mechanisms underlying the tolerogenic properties of
this molecule, we analysed different preparations of the recombinant alpha
gliadin, alone or conjugated to the adjuvant cholera toxin (CT), by in vitro
challenge with spleen CD4+ T cells from gliadin-sensitized DQ8 tg mice. We found
that a partially purified preparation of recombinant alpha-gliadin (r-gliadin)
induced a significantly higher production of IFN-gamma than native gliadin as
well as HPLC purified r-gliadin. Interestingly, r-gliadin, but not HPLC purified
r-gliadin, stimulated the gliadin-specific expression of IL-10 in CD4+ T cells.
No significant cytotoxic effect was induced by r-gliadin in MODE-K cells, a
murine model of enterocytes. Notably, a conjugate CT-r-gliadin failed in
stimulating IFN-gamma, whereas IL-10 secretion was still induced in gliadin
specific CD4+ T cells. In conclusion, our results showed that DCs, pulsed with CT
r-gliadin in vitro, could modulate the ongoing Th1-like T cell response toward
wheat gliadin. This finding provides new insight into the design of
immunomodulatory protocols potentially useful for CD.
PMID- 28511838
TI - Supra-annular Valve-in-Valve implantation reduces blood stasis on the
transcatheter aortic valve leaflets.
AB - Leaflet thrombosis following transcatheter aortic valve replacement (TAVR) and
Valve-in-Valve (ViV) procedures has been increasingly recognized. This study
aimed to investigate the effect of positioning of the transcatheter aortic valve
(TAV) in ViV setting on the flow dynamics aspect of post-ViV thrombosis by
quantifying the blood stasis in the intra-annular and supra-annular settings. To
that end, two idealized computational models, representing ViV intra-annular and
supra-annular positioning of a TAV were developed in a patient-specific geometry.
Three-dimensional flow fields were then obtained via fluid-solid interaction
modeling to study the difference in blood residence time (BRT) on the TAV
leaflets in the two settings. At the end of diastole, a strip of high BRT (?1.2s)
region was observed on the TAV leaflets in the ViV intra-annular positioning at
the fixed boundary where the leaflets are attached to the frame. Such a high BRT
region was absent on the TAV leaflets in the supra-annular positioning. The
maximum value of BRT on the surface of non-, right, and left coronary leaflets of
the TAV in the supra-annular positioning were 53%, 11%, and 27% smaller compared
to the intra-annular positioning, respectively. It was concluded that the
geometric confinement of TAV by the leaflets of the failed bioprosthetic valve in
ViV intra-annular positioning increases the BRT on the leaflets and may act as a
permissive factor in valvular thrombosis. The absence of such a geometric
confinement in the ViV supra-annular positioning leads to smaller BRT and
subsequently less likelihood of leaflet thrombosis.
PMID- 28511839
TI - The implication of the osteolysis threshold and interfacial gaps on
periprosthetic osteolysis in cementless total hip replacement.
AB - Osteolysis around joint replacements may develop due to migration of wear
particles from the joint space into gaps between the interface bone and the
implant where they can accumulate in high concentrations to cause tissue damage.
Osteolysis may appear in various postoperative times and morphological shapes
which can be generalized into linear and focal. However, there are no clear
explanations on the causes of such variations. Patients' degree of sensitivity to
polyethylene particles (osteolysis thresholds), the local particle concentration
and the access route provided by the interface gaps have been described as
determining factors. To study their effects, a 2D computational fluid dynamics
model of the hip joint capsule in communication with an interfacial gap and the
surrounding bone was employed. Particles were presented using a discrete phase
model (DPM). High capsular fluid pressure was considered as the driving force for
particle migration. Simulations were run for different osteolysis thresholds
ranging from 5*108 to 1*1012 particle number per gram of tissue and fibrous
tissue generation in osteolytic lesion due to particles was simulated for the
equivalent of ten postoperative years. In patients less sensitive to polyethylene
particles (higher threshold), osteolysis may be linear and occur along an
interfacial gap in less than 5% of the interfacial tissue. Focal osteolysis is
more likely to develop in patients with higher sensitivity to polyethylene
particles at distal regions to an interfacial gaps where up to 80% of the
interfacial tissue may be replaced by fibrous tissue. In these patients, signs of
osteolysis may also develop earlier (third postoperative year) than those with
less sensitivity who may show very minor signs even after ten years. This study
shows the importance of patient sensitivity to wear particles, the role of
interfacial gaps in relation to morphology and the onset of osteolysis.
Consequently, it may explain the clinically observed variation in osteolysis
development.
PMID- 28511840
TI - Quantitative assessment of trunk deformation during running.
AB - The trunk has a multi-segmental structure and is composed of the cervical,
thoracic, and lumber spines and surrounding soft tissue elements; this allows
flexible deformation during dynamic movements. The purpose of this study was to
quantitatively assess trunk deformation during dynamic movement. Ten male
subjects performed running at four different speeds: 8km/h, 10km/h, 12km/h, and
14km/h. Forty reflective markers were placed on the backs of these individuals to
define 56 small triangular areas, and three-dimensional kinematic data was
recorded with a motion capture system. The coefficients of variation (CV) of the
horizontal and vertical lengths between two adjacent markers and the standard
deviation (SD) of the normal vectors of triangular areas were calculated as
measures for translational and angular trunk deformation, respectively. Up to
about 14% of CV and 78 degrees of SD appeared as the measure of translational
and angular deformation, respectively. These results imply that the trunk
underwent a significant amount of position-specific deformation. These findings
would be useful in the construction of an optimal trunk segment model to
represent the complex and flexible trunk movement during dynamic movements.
PMID- 28511841
TI - A method for isolating cortical interneurons sharing the same birthdays for gene
expression studies.
AB - The two neuronal populations in the cortex, pyramidal neurons and interneurons,
can be separated based on neurotransmitter identity, however, within this
segregation a large degree of diversity exists. Investigations into the molecular
diversity of neurons are impeded by the inability to isolate cell populations
born at different times for gene expression analysis. Developing interneurons may
be distinguished by the expression of Glutamic Acid Decarboxylase-67 (GAD67).
Neuronal birthdating using nucleoside analogs is an effective means of
identifying coetaneous interneurons. Using these two features, neurotransmitter
identity and birthdating, we have developed a method to isolate migrating
interneurons using fluorescent-activated cell sorting (FACS) for RNA extraction
and gene expression analysis. We utilized 5-ethynyl-2'-deoxyuridine (EdU) to
birthdate interneuron cohorts and the GAD67 knock-in GFP transgenic mice to
identify interneurons. In combination, we achieved simultaneous detection of GFP
and EdU signals during FACS sorting of coetaneous interneurons with minimum loss
of RNA integrity. RNA quality was deemed to be satisfactory by quantitative
polymerase chain reaction (qPCR) for the interneuron-specific transcript Gad67.
PMID- 28511842
TI - Response to the letter to the editor regarding "Quantitative study of voice
dysfunction after thyroidectomy".
PMID- 28511843
TI - Interpellating recovery: The politics of 'identity' in recovery-focused
treatment.
AB - Much research tends to treat alcohol and other drug 'recovery' as a process of
positive identity change and development. In this article, we depart from this
dominant approach by examining how the social and material practices of alcohol
and other drug treatment are themselves active in the constitution of 'recovery
identity'. Using Judith Butler's theorisation of interpellation, we examine the
accounts of treatment experiences and practices provided in interviews with
people who inject drugs. In contrast to the existing literature, we argue that
the 'recovering addict' is a socially produced category rather than a coherent
psychological identity. We consider the production of this category in relation
to three dynamics identified in the data: (1) the tendency to materialise
treatment subjects as both disordered and as 'in control' of these disorders; (2)
the production of treatment subjects as enmeshed in suspect social relationships
and therefore requiring surveillance as well as social support; and (3)
treatment's particular enactment of social context such that it erases
stigmatisation and marginalisation and paradoxically performs subjects as
entirely individually responsible for relinquishing drug use. These dynamics
produce capacities and attributes often ascribed to identity but which are better
understood as articulations of epistemological disorder in the state of knowledge
about addiction, and its expression in treatment. By way of conclusion, we
question the utility of 'recovery identity', conventionally defined, in providing
a rationale for treatment.
PMID- 28511844
TI - Pediatric Nurse Practitioners in the Emergency Department: Implications for
Education and Research.
AB - The use of pediatric nurse practitioners in emergency departments is common in
the United States. Defining competencies that are specific to the wide span of
urgent and emergent pediatric conditions, along with a recognized practice
standard for education and specialty certification for pediatric nurse
practitioners practicing in emergency care, is needed. Pediatric emergency
departments require a team of providers with a skill set that aligns with each
patient's needs. The use of qualified pediatric nurse practitioners on these
teams, both primary care and acute care certified, to provide care to these
children is expanding, with implications for education and research.
PMID- 28511845
TI - miR-205 is a critical regulator of lacrimal gland development.
AB - The tear film protects the terrestrial animal's ocular surface and the lacrimal
gland provides important aqueous secretions necessary for its maintenance.
Despite the importance of the lacrimal gland in ocular health, molecular aspects
of its development remain poorly understood. We have identified a noncoding RNA
(miR-205) as an important gene for lacrimal gland development. Mice lacking miR
205 fail to properly develop lacrimal glands, establishing this noncoding RNA as
a key regulator of lacrimal gland development. Specifically, more than half of
knockout lacrimal glands never initiated, suggesting a critical role of miR-205
at the earliest stages of lacrimal gland development. RNA-seq analysis uncovered
several up-regulated miR-205 targets that may interfere with signaling to impair
lacrimal gland initiation. Supporting this data, combinatorial epistatic deletion
of Fgf10, the driver of lacrimal gland initiation, and miR-205 in mice
exacerbates the lacrimal gland phenotype. We develop a molecular rheostat model
where miR-205 modulates signaling pathways related to Fgf10 in order to regulate
glandular development. These data show that a single microRNA is a key regulator
for early lacrimal gland development in mice and highlights the important role of
microRNAs during organogenesis.
PMID- 28511846
TI - Measuring the differences in work ratios between pediatric and adult
ophthalmologic examinations.
AB - PURPOSE: To assess the differences in work needed for pediatric and adult
ophthalmologic examinations. METHODS: Seven ophthalmology residents conducted
slit-lamp and refraction examinations on children 3-7 years of age and adults 20
69 years of age. The examiners reported the magnitude estimate (ME) of their work
in relation to two references (cross-reference ME): average adult examination and
average pediatric examination. The examination time was also measured. RESULTS:
For the slit-lamp examination, 50 children and 58 adults were recruited. The ME
was 1.45 (95% CI, 1.30-1.62) times higher for the pediatric examinations than for
the adult examinations when the reference was an average adult case. With respect
to time, the pediatric examinations took 1.22 (95% CI, 1.06-1.41) times longer
than the adult examinations. For the refraction examinations, 58 children and 96
adults were recruited. The ME was 1.35 (95% CI, 1.21-1.52) times higher for the
pediatric examinations. The pediatric examination took 1.32 (95% CI, 1.16-1.50)
times longer than the adult examination. The cross-reference ME ratios measuring
the pediatric over adult examinations against both the pediatric and adult
reference cases were equivalent in both the slit-lamp and the refraction
examinations; however, the ME and time ratios of the pediatric over the adult
examinations were not equivalent for the slit-lamp or for the refraction
examinations. CONCLUSIONS: The cross-reference ME showed that pediatric
ophthalmologic examinations require more work than the adult examination with
validity and reliability. The time estimate was insufficient as a single
indicator for work estimation.
PMID- 28511847
TI - Moving with the times.
PMID- 28511848
TI - Intense resistance exercise increases peripheral brain-derived neurotrophic
factor.
AB - OBJECTIVES: Brain-derived neurotrophic factor (BDNF) has been shown to increase
in an intensity dependent manner in response to aerobic exercise. However,
previous research investigating the use of resistance exercise to increase BDNF
levels has been less conclusive, likely due to the low intensity nature of
traditional resistance exercise programs. This study examined the influence of
acute resistance exercise to-fatigue on serum BDNF levels and blood lactate.
DESIGN: Acute crossover study. METHODS: Eleven untrained to intermediately
trained males (age: 25.0+/-1.3 year) and five untrained females (age: 23.2+/-1.1
year) were recruited to undertake two bouts of resistance exercise. Strength
(five sets of five repetitions, 180s recovery) and hypertrophy (three sets of ten
repetitions, 60s recovery) based resistance exercise was implemented to-fatigue
to examine the effect on serum BDNF and blood lactate levels immediately post-,
and 30min post-exercise. RESULTS: An interaction (p<0.01; ES=0.52) was observed
between conditions immediately post-exercise, with hypertrophy resulting in
significantly greater BDNF levels when compared with strength exercise. Changes
in lactate and BDNF from baseline to post- exercise were positively correlated
following hypertrophy exercise (r=0.70; p<0.01), but not correlated following
strength exercise (r=0.18; p=0.56). CONCLUSIONS: The use of a to-fatigue
hypertrophy based resistance exercise protocol provides the necessary stimulus to
increase peripheral serum BDNF. Mechanistically, the presence of lactate does not
appear to drive the BDNF response during resistance exercise.
PMID- 28511849
TI - Cardiometabolic healthy obesity paradigm and all-cause mortality risk.
AB - OBJECTIVE: To examine the cardiometabolic healthy obesity paradigm as it relates
to all-cause mortality risk, with effect moderation evaluated for physical
activity and demographic characteristics. METHODS: Data from the 1999-2006 NHANES
were used. The analytic sample included 7579 dietary fasting adults (20+ yrs).
All-cause mortality was linked with participant data from the National Death
Index. Metabolic health was based on fasting levels of triglycerides, high
density lipoprotein cholesterol, glucose and blood pressure. Weight status was
determined from measured height and weight. Physical activity was assessed via
self-report. Six mutually exclusive groups were evaluated, including 1)
Metabolically Healthy and Normal Weight (Referent), 2) Metabolically Healthy and
Overweight, 3) Metabolically Healthy and Obese, 4) Metabolically Abnormal and
Normal Weight, 5) Metabolically Abnormal and Overweight, and 6) Metabolically
Abnormal and Obese. A Cox proportional hazards model was used to evaluate the
association between these 6 groups and all-cause mortality. RESULTS: The
unweighted median follow-up was 103months; 770,568 person-months occurred with an
incidence rate of 1.18 deaths per 1000 person-months. When compared to those who
were metabolically healthy and of normal BMI, all other metabolic and weight
configurations had an increased mortality risk. There was no evidence of effect
modification by physical activity or demographic characteristics. CONCLUSIONS:
These findings emphasize the importance of optimizing body habitus and increasing
public awareness of the detrimental effects of metabolic abnormalities.
PMID- 28511850
TI - Asteroid Hyalosis.
PMID- 28511851
TI - Sex differences in association between decreased glomerular filtration rate and
prolongation of corrected QT interval in general Chinese population.
PMID- 28511852
TI - Introducing a checking technician allows pharmacists to spend more time on
patient-focused activities.
AB - BACKGROUND: Internationally there is an increasing focus on the clinical and
cognitive services that pharmacists can provide. Lack of time has been identified
as a barrier to pharmacists increasing their clinical activities. Within the
pharmacy workplace there are many tasks that can only be performed by a
pharmacist. The final accuracy check of a dispensed prescription is currently the
sole responsibility of pharmacists in New Zealand. This takes up a significant
amount of time during a pharmacist's work day. The introduction of a checking
technician role has been suggested to allow pharmacists more time to do more
patient focused work. AIM/OBJECTIVE: To investigate the amount of time pharmacy
staff spend on specific activities and to establish whether the introduction of a
checking technician into twelve pilot sites increased the amount of time that the
pharmacists could spend on patient focused activities. METHODS: This study
utilised a self-reported work sampling technique in twelve pilot sites, selected
from both the hospital and community settings. Work sampling using an electronic
device was conducted at two time-points (before the implementation of a Pharmacy
Accuracy Checking Technician (PACT) role and when the PACT was in place). Data
was collected at 10 min intervals for the period of five days, a working week.
Tasks were grouped into patient focused, dispensing and personal activities.
RESULTS: The introduction of the PACT into the pilot sites saw a mean increase of
19% in pharmacists' patient focused activities and a mean 20% decrease in
dispensing activities. CONCLUSION: The introduction of a checking technician role
into New Zealand pharmacies demonstrated the potential to provide pharmacists
with more time to spend on patient focused activities.
PMID- 28511853
TI - Immunologic evaluation of 10 different adjuvants for use in vaccines for chickens
against highly pathogenic avian influenza virus.
AB - Avian influenza viruses (AIV) are a threat to poultry production worldwide.
Vaccination is utilized as a component of control programs for both high
pathogenicity (HP) and low pathogenicity (LP) AIV. Over 95% of all AIV vaccine
used in poultry are inactivated, adjuvanted products. To identify the best
formulations for chickens, vaccines were prepared with beta-propiolactone (BPL)
inactivated A/British Columbia/314514-1/2004 H7N3 LP AIV using ten commercially
available or experimental adjuvants. Each vaccine formulation was evaluated for
immunogenicity in chickens. Challenge studies with an antigenically homologous
strain of HPAIV were conducted to compare protection against mortality and
measure reductions in virus levels in oral swabs. The four best adjuvants from
the studies with BPL inactivated antigen were selected and tested identically,
but with vaccines prepared from formalin inactivated virus. Mineral and vegetable
oil based adjuvants generally induced the highest antibody titers with 100%
seroconversion by 3weeks post vaccination. Chitosan induced positive antibody
titers in 100% of the chickens, but the titers were significantly lower than
those of most of the oil based adjuvants. Antibody levels from calcium phosphate
and alginate adjuvanted groups were similar to those of non-adjuvanted virus. All
groups that received adjuvanted vaccines induced similar levels of protection
against mortality (0-20%) except the groups vaccinated with calcium phosphate
adjuvanted vaccines, where mortality was similar (70%) to groups that received
non-adjuvanted inactivated virus or no vaccine (60-100% mortality). Virus
shedding in oral swabs was variable among the treatment groups. Formalin
inactivated vaccine induced similar antibody titers and protection against
challenge compared to BPL inactivated vaccine groups. These studies support the
use of oil adjuvanted vaccines for use in the poultry industry for control for
AIV.
PMID- 28511854
TI - Acot1 is a sensitive indicator for PPARalpha activation after perfluorooctanoic
acid exposure in primary hepatocytes of Sprague-Dawley rats.
AB - Perfluorooctanoic acid (PFOA) is one of the most commonly detected and persistent
perfluoroalkyl substances (PFASs) found in the environment. We found that cell
viability and intracellular oxidant stress increased in primary rat hepatocytes
exposed to PFOA (100MUM PFOA, 24h), and mitochondrial superoxide increased from
6.25MUM PFOA treatment group. To screen for sensitive indicators in mRNA level,
we investigated global transcriptome profile alteration after PFOA exposure using
RNA-sequencing (RNA-seq) in primary rat hepatocytes, and identified 177 gene
transcripts (158 upregulated, 19 downregulated) as significantly changed after
exposure to 100MUM of PFOA for 24h (fold change >=2, FDR<0.05). Quantitative PCR
(qPCR) and RNA-fluorescence in situ hybridization (RNA-FISH) assays were
conducted after PFOA treatment at various doses (0, 0.4, 1.56, 6.25, 25, and
100MUM) and times (6, 12, 18, 24, 48, and 96h). Acot1 transcripts increased
significantly in the 100MUM PFOA group (4500-fold) after 24h of exposure, and
increased remarkably for all time points (24, 48, 72 and 96h) after exposure to
6.25MUM. Acot1 also responded to lower PFOA doses, with a significant increase
found after exposure to 0.4MUM for 96h. These results imply Acot1 could serve as
a sensitive indicator for PPARalpha activation after PFOA exposure in primary rat
hepatocytes.
PMID- 28511856
TI - Measurement of 15N longitudinal relaxation rates in 15NH4+ spin systems to
characterise rotational correlation times and chemical exchange.
AB - Many chemical and biological processes rely on the movement of monovalent cations
and an understanding of such processes can therefore only be achieved by
characterising the dynamics of the involved ions. It has recently been shown that
15N-ammonium can be used as a proxy for potassium to probe potassium binding in
bio-molecules such as DNA quadruplexes and enzymes. Moreover, equations have been
derived to describe the time-evolution of 15N-based spin density operator
elements of 15NH4+ spin systems. Herein NMR pulse sequences are derived to select
specific spin density matrix elements of the 15NH4+ spin system and to measure
their longitudinal relaxation in order to characterise the rotational correlation
time of the 15NH4+ ion as well as report on chemical exchange events of the
15NH4+ ion. Applications to 15NH4+ in acidic aqueous solutions are used to cross
validate the developed pulse sequence while measurements of spin-relaxation rates
of 15NH4+ bound to a 41kDa domain of the bacterial Hsp70 homologue DnaK are
presented to show the general applicability of the derived pulse sequence. The
rotational correlation time obtained for 15N-ammonium bound to DnaK is similar to
the correlation time that describes the rotation about the threefold axis of a
methyl group. The methodology presented here provides, together with the previous
theoretical framework, an important step towards characterising the motional
properties of cations in macromolecular systems.
PMID- 28511855
TI - Clinical correlates and prognostic impact of impaired iron storage versus
impaired iron transport in an international cohort of 1821 patients with chronic
heart failure.
AB - AIMS: To define iron deficiency in chronic heart failure (CHF), both,
ferritin<100MUg/L (indicating reduced iron storage) and transferrin saturation
(TSAT)<20% (indicating reduced iron transport) are used. The aim of the study was
to evaluate clinical outcomes and prognosis of either low ferritin or low TSAT in
patients with CHF. METHODS AND RESULTS: We evaluated the clinical impact of
impaired iron storage (IIS) and impaired iron transport (IIT) either alone or in
combination compared to patients with normal iron status (NIS), in an
international cohort of 1821 patients with CHF with a mean age of 66+/-13years
and mean left ventricular ejection fraction of 35%+/-15. Isolated IIS was
observed in 219 patients (12%), isolated IIT in 454 (25%) and coexistence of both
conditions (IIS+IIT) were seen in 389 (21%). In adjusted models we found that
patients with IIS+IIT and patients with isolated IIT had higher NT-proBNP levels
(OR 2.2 [1.6-3.1] and OR 2.1 [1.5-2.9] respectively) and worse quality of life
(OR 1.8 [1.2-2.7] and OR 1.7 [1.2-2.5] respectively) compared with isolated IIS.
Multivariate Cox analyses showed that IIS+IIT and isolated IIT were independently
associated with all-cause mortality (OR 1.41 [1.06-1.86] and OR 1.47 [1.13-1.92]
respectively). Patients with isolated IIS did not differ from NIS patients in
terms of severity or outcomes. CONCLUSIONS: Impaired iron transport alone or in
combination with impaired iron storage is associated with worse clinical profile
and increased risk of mortality in patients with CHF. Patients with isolated
impaired iron storage may have a milder form of iron deficiency.
PMID- 28511857
TI - Posterior microphthalmos, retinitis pigmentosa and optic disc drusen with white
dots. A case report.
AB - OBJECTIVE: To present the case of a patient with a posterior microphthalmos-optic
disc drusen-retinitis pigmentosa syndrome associated, for the first time, with
white dots in the posterior pole. METHODOLOGY: The posterior microphthalmos,
retinitis pigmentosa and optic disc drusen syndrome was described for the first
time in literature in 1991. Later, it was associated with a pattern of foveal
thickening and/or foveoschisis. Different forms of mutations on chromosomes 11
and 14 have been identified as being responsible for the appearance of this
syndrome, but the inheritance pattern is unknown. DISCUSSION: The case is
reported of a 37 year-old man, with no personal or family history of interest,
diagnosed with this syndrome in association with white dots in the posterior
pole. Such a morphological association has never been published before in
literature. CONCLUSION: The posterior microphthalmos, retinitis pigmentosa and
optic disc drusen syndrome is a very rare entity, and has never been described
associated with white dots in the posterior pole. More case reports are needed to
establish clear patterns of both the disease and inheritance.
PMID- 28511860
TI - First-Trimester Fetal Echocardiography: Identification of Cardiac Structures for
Screening from 6 to 13 Weeks' Gestational Age.
AB - BACKGROUND: Early fetal echocardiography (FE), performed at 12 to 16 weeks'
gestational age (GA), can be used to screen for fetal heart disease akin to that
routinely performed in the second trimester. The efficacy of FE at earlier GAs
has not been as well explored, particularly with recent advances in ultrasound
technology. The aim of this study was to evaluate the efficacy of early FE in
assessing fetal heart structure, and the added benefit of color Doppler (CD),
from as early as 6 weeks through to 13+6 weeks' GA. METHODS: Pregnant women were
prospectively recruited for first-trimester FE. All underwent two-dimensional
(2D) cardiac imaging combined with CD assessment, and all were offered second
trimester fetal echocardiographic evaluations. Fetal cardiac anatomy was assessed
both in real time during FE and additionally offline by two separate reviewers.
RESULTS: Very early FE was performed in 202 pregnancies including a total of 261
fetuses, with 92% (n = 241) being reassessed at >=18 weeks' GA. Mean GA at FE was
10+6 weeks (range, 6+1 to 13+6 weeks). Transabdominal scanning was used in all
cases, and transvaginal scanning was used additionally in most at <11 weeks' GA
(n = 103 of 117 [88%]). There was stepwise improvement in image resolution of the
fetal heart in those pregnancies that presented at later gestation for
assessment. CD assisted with definition of cardiac anatomy at all GAs. A four
chambered heart could be identified in 52% of patients in the eighth week (n = 12
of 23), improving to 80% (n = 36 of 45) in the 10th week and 98% (n = 57 of 58)
by the 11th week. The inferior vena cava was visualized by 2D imaging in only 4%
(n = 1 of 23) in the eighth week, increasing to 13% (n = 6 of 45) by the 10th
week and 80% (n = 25 of 31) by the 13th week. CD improved visualization of the
inferior vena cava at earlier GAs to >80% (n = 37 of 45) from 10 weeks. Pulmonary
veins were not visualized by either 2D imaging or CD until after the 11th week.
Both cardiac outflow tracts could be visualized by 2D imaging in the minority
from 8+0 to 10+6 weeks (n = 18 of 109 [16%]) but were imaged in most from 11+0 to
13+6 weeks (n = 114 of 144 [79%]). CD imaging improved visualization of both
outflow tracts to 64% (n = 29 of 45) in the 10th week. On 2D imaging alone, both
the aortic and ductal arches were seen in only 29% of patients in the 10th week
(n = 13 of 45), increasing to 58% when CD was used (58% [n = 26 of 45]) and to
>80% (n = 47 of 58) using CD in the 11th week. CONCLUSIONS: Very early FE, from
as early as 8 weeks, can be used to assess cardiac structures. The ability to
image fetal heart structures between 6 and 8 weeks is currently nondiagnostic.
The use of CD significantly increases the detection of cardiac structures on
early FE. The ideal timing of complete early FE, excluding pulmonary vein
assessment, appears to be after 11 weeks' GA.
PMID- 28511859
TI - Reference Ranges and Regional Patterns of Left Ventricular Strain and Strain Rate
Using Two-Dimensional Speckle-Tracking Echocardiography in a Healthy Middle-Aged
Black and White Population: The CARDIA Study.
AB - BACKGROUND: Strain and strain rate are sensitive markers of left ventricular (LV)
myocardial function. The aim of this study was to assess reference ranges and
regional patterns of LV strain and strain rate using two-dimensional speckle
tracking echocardiography in a large population of black and white subjects.
METHODS: This study involved a retrospective review of prospectively collected
images in 557 participants in the Coronary Artery Risk Development in Young
Adults study who remained healthy at the year 25 examination. LV deformation
parameters were measured in apical four-chamber, apical two-chamber, and
parasternal short-axis views in 509, 391, and 521 subjects, respectively.
RESULTS: Patients' mean age was 49.6 +/- 3.6 years, 61.6% were women, and 69.5%
were white. White women showed the highest LV systolic and diastolic deformation
values, reflected by a more negative reference range for apical four-chamber
longitudinal strain (-16.4%; 95% prediction interval [PI], -20.8% to -12.0%) and
a higher positive reference range for early diastolic strain rate (0.93 1/sec;
95% PI, 0.41 to 1.46 1/sec), respectively. The lowest LV systolic and diastolic
deformation values were found in black men, with apical four-chamber longitudinal
strain (14.7%; 95% PI, -19.1% to -10.3%) and early diastolic strain rate (0.79
1/sec; 95% PI, 0.42 to 1.16 1/sec). Absolute strain increased from the epicardium
toward the endocardium. A base-to-apex gradient of longitudinal strain toward the
apex was exhibited in inferior and inferoseptal regions and, in contrast, in the
opposite direction in anterior and anterolateral walls. Sex had the strongest
influence on LV deformation variability. CONCLUSIONS: Strain and strain rate
reference values were sex and race related. White women showed the highest
reference ranges for LV deformation, while the lowest values were found in black
men. Significant layer- and level-specific patterns in regional LV deformation
were identified.
PMID- 28511861
TI - Speckle-Tracking Layer-Specific Analysis of Myocardial Deformation and Evaluation
of Scar Transmurality in Chronic Ischemic Heart Disease.
AB - BACKGROUND: Identification of the extent of scar transmurality in chronic
ischemic heart disease is important because it correlates with viability. The aim
of this retrospective study was to evaluate whether layer-specific two
dimensional speckle-tracking echocardiography allows distinction of scar presence
and transmurality. METHODS: A total of 70 subjects, 49 with chronic ischemic
cardiomyopathy and 21 healthy subjects, underwent two-dimensional speckle
tracking echocardiography and late gadolinium-enhanced cardiac magnetic
resonance. Scar extent was determined as the relative amount of hyperenhancement
using late gadolinium-enhanced cardiac magnetic resonance in an 18-segment model
(0% hyperenhancement = normal; 1%-50% = subendocardial scar; 51%-100% =
transmural scar). In the same 18-segment model, peak systolic circumferential
strain and longitudinal strain were calculated separately for the endocardial and
epicardial layers as well as the full-wall myocardial thickness. RESULTS: All
strain parameters showed cutoff values (area under the curve > 0.69) that allowed
the discrimination of normal versus scar segments but not of transmural versus
subendocardial scars. This was true for all strain parameters analyzed, without
differences in efficacy between longitudinal and circumferential strain and
subendocardial, subepicardial, and full-wall-thickness strain values.
Circumferential and longitudinal strain in normal segments showed transmural and
basoapical gradients (greatest values at the subendocardial layer and apex). In
segments with scar, transmural gradient was maintained, whereas basoapical
gradient was lost because the reduction of strain values in the presence of the
scar was greater at the apex. CONCLUSIONS: The two-dimensional speckle-tracking
echocardiographic values distinguish scar presence but not transmurality; thus,
they are not useful predictors of scar segment viability. It remains unclear why
there is a greater strain value reduction in the presence of a scar at the apical
level.
PMID- 28511858
TI - Reduced Myocardial Reserve in Young X-Linked Muscular Dystrophy Mice Diagnosed by
Two-Dimensional Strain Analysis Combined with Stress Echocardiography.
AB - BACKGROUND: Early, sensitive, and reproducible evaluation of left ventricular
function is imperative for the diagnosis of cardiac dysfunction in patients with
Duchene muscular dystrophy. The aim of this study was to test the hypothesis that
combining two-dimensional strain analysis with catecholamine stress could be a
sensitive method for detecting early cardiac dysfunction. METHODS: Mdx
(C57BL/10ScSn-Dmdmdx/J, a mouse model of DMD) and control (C57BL/10ScSn) mice
were studied with conventional M-mode and high-frequency ultrasound-based two
dimensional speckle-tracking echocardiography using long- and short-axis images
of the left ventricle at baseline and after intraperitoneal isoprenaline (ISO)
administration (2 MUg/g body weight). RESULTS: Conventional M-mode analysis
showed no differences in left ventricular fractional shortening, wall thickness,
or internal diameter at diastole between mdx and control mice before the age of 6
months. ISO increased left ventricular ejection fraction and fractional
shortening to the same extent in mdx and control mice at young ages (3, 4, and 5
months). No differences in basal peak systolic strain (PSS) but increased SDs of
times to PSS between young mdx and control mice were found. After ISO, PSS and
percentile changes of PSS were significantly diminished in mdx mice compared with
control mice at young ages. ISO increased the normalized maximum difference of
times to PSS in young mdx mice but not in young control mice, suggesting that ISO
reduces cardiac contractile synchrony in young mdx mice. CONCLUSIONS: This study
suggests that catecholamine stress coupled with two-dimensional strain analysis
is a feasible and sensitive approach for detecting early onset of cardiac
dysfunction, which is instrumental for early diagnosis of cardiac dysfunction and
early treatment.
PMID- 28511862
TI - Effect of different concentrations of egg yolk and virgin coconut oil in Tris
based extenders on chilled and frozen-thawed bull semen.
AB - The aim of this study was to evaluate the effects of 8% virgin coconut oil (VCO)
combined with different percentages of egg yolk in Tris extender on the quality
of chilled and frozen-thawed bull semen. A total of 24 ejaculates from four bulls
were collected using an electroejaculator. Semen samples were diluted with 8% VCO
in Tris extender which contained different concentrations 0% (control), 4%, 8%,
12%, 16% and 20% egg yolk. The diluted semen samples were divided into two
fractions: one was chilled and stored at 4 degrees C until evaluation after 24,
72, and 144h; the second fraction was processed by chilling for 3h at 4 degrees C
to equilibrate, then packaged in 0.25ml straws and frozen and stored in liquid
nitrogen at -196 degrees C until evaluation after 7 and 14 days. Both chilled and
frozen semen samples were then thawed at 37 degrees C and assessed for general
motility using computer-assisted semen analysis (CASA), viability, acrosome
integrity, and morphology (eosin-nigrosin), membrane integrity (hypo-osmotic
swelling test) and lipid peroxidation (thiobarbituric acid-reactive substances
(TBARS)). The results indicate treatments with 8%, 12%, 16% and 20% egg yolk with
8% VCO had greater sperm quality (P<0.05) as compared with the control. The
treatment with 20% egg yolk had the greatest sperm quality (P<0.05) among the
treated groups for both chilled and frozen-thawed semen. In conclusion, the use
of 8% VCO combined with 20% egg yolk in a Tris-based extender enhanced the values
for chilled and frozen-thawed quality variables of bull sperm.
PMID- 28511863
TI - Expression of TNF-alpha system members in bovine ovarian follicles and the
effects of TNF-alpha or dexamethasone on preantral follicle survival, development
and ultrastructure in vitro.
AB - This study was conducted to detect the protein expression of TNF-alpha system
members (TNF-alpha/TNFR1/TNFR2) in bovine ovarian follicles and to evaluate the
effects of TNF-alpha or dexamethasone on the survival and growth of primordial
follicles in vitro, as well as on gene expression in cultured ovarian tissue. It
was hypothesized that TNF-alpha induces follicular atresia in ovarian tissues
cultured in vitro, and that dexamethasone suppresses the production of endogenous
TNF-alpha, which can improve follicle viability in vitro. Ovarian fragments were
cultured for 6days in alpha-MEM+ supplemented with TNF-alpha (0, 1, 10, 100 or
200ng/ml) or dexamethasone (0, 1, 10, 100 or 200ng/ml). After culture, the
expression of mRNAs for BCL-2, BAX, P53, TNF-alpha, and CASP3 and CASP6 were
evaluated. Immunohistochemical results showed that the TNF-alpha system members,
were detected in bovine preantral and antral follicles. After 6days, the TNF
alpha (10ng/ml) treatment reduced the percentage of normal preantral follicles
and increased the number of TUNEL-positive cells in cultured tissue.
Dexamethasone (10ng/ml) during 6days of culture did maintain the percentage of
normal follicles and the ultrastructure of follicles, while the presence of TNF
alpha or dexamethasone did not influence primordial follicle activation. However,
TNF-alpha or dexamethasone had no effect on the levels of mRNA for P53, BCL-2,
BAX and CASP6, in cultured tissues, but the presence of dexamethasone reduced the
levels of CASP3 compared to ovarian slices cultured in control medium (alpha
MEM+). In conclusion, proteins of the TNF-alpha system are expressed at different
bovine follicle stages. The addition of TNF-alpha in culture reduces follicle
survival and increases the number of apoptotic cells in ovarian tissue, while the
presence of dexamethasone maintains follicle ultrastructure in cultured tissue.
PMID- 28511864
TI - Metabolism and disposition of [14C]-methylcyclosiloxanes in rats.
AB - Octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) are low
molecular weight cyclic volatile methyl siloxanes (cVMSs) primarily used as
intermediates or monomers in the production of high molecular weight silicone
polymers. The use of D4 as a direct ingredient in personal care products has
declined significantly over the past 20 years, although it may be present as a
residual impurity in a variety of consumer products. D5 is still used as an
intentional ingredient in cosmetics, consumer products and in dry cleaning.
Persons who may be exposed include occupational exposure for workers, and
potential inhalation or dermal exposure for consumers and the general public.
Because of the diverse use, especially of D5, and the potential for human
exposure, a comprehensive program was undertaken to understand the kinetics,
metabolism, enzyme induction and toxicity of D4 and D5 in rats following relevant
routes of exposure. Physiologically based pharmacokinetic (PBPK) models utilizing
these studies have been reported for D4 and D5 in the rat and human following
dermal and inhalation exposures, with the oral uptake component of the model
being limited in its description. Data from high dose oral studies in corn oil
and simethicone vehicles and neat were used in the D4/D5 harmonized PBPK model
development. It was uncertain if the inability to adequately describe the oral
uptake was due to unrealistic high doses or unique aspects of the chemistry of
D4/D5. Low dose studies were used to provide data to refine the description of
oral uptake in the model by exploring the dose dependency and the impact of a
more realistic food-like vehicle. Absorption, distribution, metabolism and
elimination (ADME) of D4 and D5 was determined following a single low oral gavage
dose of 14C-D4 and 14C-D5 at 30 and 100mg/kg body weight (bw), respectively, in a
rodent liquid diet. Comparison of the low vs. high dose oral gavage
administration of D4 and D5 demonstrated dose-dependent kinetic behavior. Data
and modeling results suggest differences in metabolism between low and high dose
administration indicating high dose administration results in or approaches non
linear saturated metabolism. These low dose data sets were used to refine the
D4/D5 multi-route harmonized PBPK model to allow for a better description of the
disposition and toxicokinetics of D4/D5 following oral exposure. With a refined
oral uptake description, the model could be used in risk assessment to better
define the internal dose of D4 and D5 following exposure to D4 and D5 via
multiple routes.
PMID- 28511865
TI - Racial and socioeconomic disparities in viral suppression among persons living
with HIV in New York City.
AB - PURPOSE: To examine differences in racial disparities across levels of
neighborhood poverty and differences in socioeconomic disparities by
race/ethnicity in viral suppression among persons living with HIV (PLWH).
METHODS: Using HIV surveillance data, we categorized and geocoded PLWH who were
in care in New York City (NYC). Multilevel binomial regression techniques were
used to model viral suppression with a two-level hierarchical structure, by
including age, transmission risk, year of diagnosis, race/ethnicity, census tract
poverty, and an interaction term of race/ethnicity and census tract poverty in
the model. RESULTS: There were 30,638 Blacks, 22,921 Hispanics, and 11,695 Whites
living with HIV and retained in care in NYC, 2014. Compared with Blacks living in
the most impoverished neighborhoods (>=30% residents living below the federal
poverty level) who had the lowest proportion of viral suppression, with 75% in
males and 76% in females, Whites living in the least impoverished neighborhoods
(<10% residents living below the federal poverty level) had the highest, with 92%
in males (prevalence ratio = 1.16; 95% confidence interval: 1.13, 1.18) and 90%
in females (PR = 1.14; 95% CI: 1.09, 1.19). CONCLUSIONS: By examining racial and
socioeconomic disparities simultaneously, we were able to detect both disparities
in viral suppression among PLWH in NYC.
PMID- 28511866
TI - Differences in mental health among young adults with borderline personality
symptoms of various severities.
AB - PURPOSE: This study examined the differences in mental health and behavioral
problems among young adults with borderline personality symptoms of various
severities. METHODS: 500 college students participated in this study. Borderline
personality symptoms were evaluated using the Taiwanese version of the Borderline
Symptom List (BSL-23). Mental health problems were assessed using the Symptom
Checklist-90-Revised Scale. Suicidality and other behavioral problems were
assessed using questions from the epidemiological version of the Kiddie Schedule
for Affective Disorders and Schizophrenia and BSL-23 Supplement. According to the
distribution of BSL-23 scores at the 25th, 50th, and 75th percentiles, the
participants were divided into 4 groups: No/Mild, Moderate, Severe, and Profound.
Analysis of variance and the chi-square test were used to compare mental health
and behavioral problems among the 4 groups. RESULTS: All mental health problems
differed significantly among the 4 groups. The severity of nearly all mental
health problems increased with that of borderline personality symptoms. The
proportions of most behavioral problems differed significantly among the 4
groups. The Profound group was more likely to have behavioral problems than the
other 3 groups. CONCLUSION: Young adults who had more severe borderline
personality symptoms had more severe mental health and behavioral problems.
PMID- 28511867
TI - Social housing and social isolation: Impact on stress indices and energy balance
in male and female Syrian hamsters (Mesocricetus auratus).
AB - Although Syrian hamsters are thought to be naturally solitary, recent evidence
from our laboratory demonstrates that hamsters may actually prefer social
contact. Hamsters increase their preference for a location associated with an
agonistic encounter regardless of whether they have "won" or "lost". It has also
been reported that social housing as well as exposure to intermittent social
defeat or to a brief footshock stressor increase food intake and body mass in
hamsters. By contrast, it has also been suggested that housing hamsters in social
isolation causes anxiety-induced anorexia and reductions in body mass selectively
in females. The purpose of this study was to determine the physiological
consequences of housing hamsters in social isolation versus in social groups.
Male and female hamsters were housed singly or in stable groups of 5 for 4weeks
after which they were weighed and trunk blood was collected. In addition, fat
pads and thymus and adrenal glands were extracted and weighed. Serum and fecal
cortisol were measured using an enzyme-linked immunoassay. Housing condition had
no effect on serum or fecal cortisol, but socially housed hamsters displayed
modest thymus gland involution. Socially housed females weighed more than did any
other group, and socially housed females and males had more fat than did socially
isolated hamsters. No wounding or tissue damage occurred in grouped hamsters.
Overall, these data suggest that Syrian hamsters tolerate both stable social
housing and social isolation in the laboratory although social housing is
associated with some alteration in stress-related and bioenergetic measures.
PMID- 28511868
TI - Tunnel malpositions in anterior cruciate ligament risk cartilaginous changes and
bucket-handle meniscal tear: Arthroscopic survey in both primary and revision
surgery.
AB - OBJECTIVES: There are not many chances to arthroscopically reassess how graft
tunnel malpositions in primary anterior cruciate ligament reconstruction (ACLR)
associate with intra-articular degeneration in revision ACLR. This study was
aimed to evaluate whether radiographic tunnel position in primary ACLR affect
cartilaginous changes and bucket-handle meniscus tears in revision ACLR. METHODS:
Thirty-five patients who underwent revision ACLR were recruited; their primary
surgeries were single-bundle reconstructions. Tunnel positions were evaluated
using the plain radiographs after primary surgery. The sagittal tunnel positions
of the femur (FP) and tibia (TP) were determined on the lateral view. The
articular cartilage was evaluated arthroscopically at primary and revision
surgery using the International Cartilage Repair Society (ICRS) score. A
progression of two grades was considered as cartilaginous changes. Meniscal tears
were evaluated with an arthroscopic probe. Logistic regression analysis was
conducted using the prevalence of cartilaginous changes or bucket-handle meniscus
tears as the dependent variable; tunnel parameters were used as the independent
variables. RESULTS: Seven patients (20.0%) had cartilaginous changes and nine
patients (25.7%) had bucket-handle tears in the medial meniscus. In logistic
regression analysis, %FP [odds ratio (OR): 1.212; P = 0.007] and the cut-off of
60% in the FP (OR: 22.000; P = 0.008) were correlated with cartilaginous changes.
%TP (OR: 1.126; P = 0.036) was correlated with the prevalence of bucket-handle
meniscus tears. CONCLUSIONS: Anterior femoral tunnel malposition in the femur was
associated with the cartilaginous changes, and posterior tibial tunnel
malposition with the development of bucket-handle meniscus tears.
PMID- 28511869
TI - Markers of the p53 pathway further refine molecular profiling in high-risk
endometrial cancer: A TransPORTEC initiative.
AB - BACKGROUND: The morphological classification of high-risk endometrial cancer is
of limited prognostic value. Recent attempts to stratify tumours according to
molecular signatures have shown considerable promise. Here we attempted to
further refine molecular classifications using markers of the p53 pathway.
METHODS: We analysed the expression of p53 as well as three downstream markers of
the p53 pathway, p21, mdm2 and phospho-p63 (pp63), by immunohistochemistry in a
series of 114 endometrial cancers (86 endometrioid, 28 non-endometrioid subtype)
with high-risk features (such as high tumour grade and deep myometrial invasion)
and correlated results with clinical outcome. The Cancer Genome Atlas (TCGA) data
were used to analyse TP63 mutations and copy-number alterations using cBioPortal.
TP53 was silenced in two endometrial cancer cell lines to study its effect on p21
and p63. RESULTS: About half of the tumours showed a p53 mutant phenotype and
there was a strong negative correlation with p21 expression. Being marker
positive for pp63 or mdm2 was associated with a significantly increased
likelihood of dying, [hazard ratios 5.93 (95% CI 2.37-7.27) and 7.48 (95% CI 3.04
9.39), respectively]. These findings were seen in both p53 wildtype and p53
mutant tumours. Only 11% of TCGA endometrial cancers had a functional TP63
alteration. Upon silencing of TP53, p21 expression was decreased in one cell
line, but no effects on p63 were observed. CONCLUSION: Markers of the p53 pathway
improve stratification of endometrial cancers and provide novel insights into the
role of this pathway in the disease.
PMID- 28511870
TI - ATP-sensitive K+ channels maintain resting membrane potential in interstitial
cells of Cajal from the mouse colon.
AB - To investigate the role of ATP-sensitive K+(KATP) channels on pacemaker activity
in interstitial cells of Cajal (ICC), whole-cell patch clamping, RT-PCR, and
intracellular Ca2+([Ca2+]i) imaging were performed in cultured colonic ICC.
Pinacidil (a K+ channel opener) hyperpolarized the membrane and inhibited the
generation of pacemaker potential, and this effect was reversed by glibenclamide
(a KATP channel blocker). RT-PCR showed that Kir 6.1 and SUR2B were expressed in
Ano-1 positive colonic ICC. Glibenclamide depolarized the membrane and increased
pacemaker potential frequency. However, 5-hydroxydecanoic acid (a mitochondrial
KATP channel blocker) had no effects on pacemaker potentials. Phorbol 12
myristate 13-acetate (PMA; a protein kinase C activator) blocked the pinacidil
induced effects, and PMA alone depolarized the membrane and increased pacemaker
potential frequency. Cell-permeable 8-bromo-cyclic AMP also increased pacemaker
potential frequency. Recordings of spontaneous intracellular Ca2+([Ca2+]i)
oscillations showed that glibenclamide increased the frequency of [Ca2+]i
oscillations. In small intestinal ICC, glibenclamide alone did not alter the
generation of pacemaker potentials, and Kir 6.2 and SUR2B were expressed in Ano-1
positive ICC. Therefore, KATP channels in colonic ICC are activated in resting
state and play an important role in maintaining resting membrane potential.
PMID- 28511871
TI - Effect of distigmine on the contractile response of guinea pig urinary bladder to
electrical field stimulation.
AB - Distigmine bromide (distigmine) is a reversible carbamate group cholinesterase
(ChE) inhibitor. Although mainly used clinically for the treatment of myasthenia
gravis, distigmine is also indicated for detrusor underactivity in Japan.
According to the pharmacological classification of distigmine, its therapeutic
effect against detrusor underactivity appears to be produced by enhanced urinary
bladder smooth muscle (UBSM) contractility due to an increased concentration of
acetylcholine between parasympathetic nerve endings and UBSM cells. However, ATP
as well as acetylcholine is also released from parasympathetic nerve endings that
dominate UBSM. The present study was thus carried out to investigate the
potentiating effects of distigmine on the two UBSM contractile components in
response to parasympathetic nerve stimulation induced by electrical field
stimulation (EFS). In isolated guinea pig UBSM tissues, EFS (1-16Hz) produced
tetrodotoxin-sensitive, frequency-dependent contractions. The contractile
responses to EFS were largely diminished by atropine (10-6M), and the remaining
contractile components in the presence of atropine were virtually abolished by
alpha,beta-methylene adenosine triphosphate (alpha,beta-mATP) (10-4M). Distigmine
(10-6M) significantly potentiated EFS-induced contractile components generated in
the presence of alpha,beta-mATP (10-4M), but did not potentiate EFS-induced
contractile components generated in the presence of atropine (10-6M). These
findings clearly indicate that distigmine strongly potentiates UBSM contraction
selectively induced by parasympathetic nerve-derived acetylcholine, suggesting a
potential mechanism by which distigmine restores detrusor underactivity.
PMID- 28511872
TI - Impairment of tear film and the ocular surface in patients with facial burns.
AB - AIM: The aim of this study is to investigate the factors affecting tear film and
ocular surface in patients with facial burns. METHODS: A total of 273 patients
with facial burns, treated at Hallym University Hangang Sacred Heart Hospital
from November 2012 to July 2015, were included. Tear break-up time (TBUT),
Schirmer's tear secretion test, fluorescein staining score (FSS), ocular surface
disease index (OSDI), and visual analogue pain score (VAS) were compared
according to burned surface area, burn site, burn cause, time since burn injury,
or lid abnormality. RESULTS: Mean age was 48.66+/-14.46years (range: 18-85). Tear
film stability was not different according to burn area, burn site, or burn
cause. Facial burn patients with lid abnormalities had shorter TBUT and higher
OSDI scores compared to no lid abnormality (p<0.001 and 0.015, independent t
test). There was no difference in TBUT and tear secretion according to area,
site, or cause of burn. FSS was different according to the area of burn (p=0.007,
ANOVA). OSDI and VAS was higher in the patients with an electrical burn compared
to thermal burn (p=0.003 and 0.024, ANOVA). CONCLUSIONS: Facial burn patients
with lid abnormalities had tear film instability and ocular discomforts.
Aggressive treatment may be of benefit in facial burn patients with lid
involvement. Electrical burn caused more severe pain compared to thermal burn.
Attention should be paid to pain control in patients with electrical burns.
PMID- 28511873
TI - Misdiagnosis of vertebral fractures on local radiographic readings of the
multicentre POINT (Prevalence of Osteoporosis in INTernal medicine) study.
AB - BACKGROUND: Osteoporotic vertebral fractures (VFs) are often misdiagnosed because
asymptomatic and occurring in the absence of specific trauma. Further, diagnostic
assessment of VFs may be suboptimal. AIM OF THE STUDY: To assess the misdiagnosis
of vertebral fractures on local radiographic readings in the cohort of patients
enrolled in the POINT study. METHODS: We enrolled hospitalised patients, admitted
for any cause to the Internal Medicine Units of 37 hospitals participating to the
cross-sectional previously published POINT study. The assessment of VFs was
performed both by local radiologists and by two expert skeletal radiologists, by
using semiquantitative method (SQ). To better evaluate mild vertebral
deformities, the two central radiologists also used the algorithm-based
qualitative assessment (ABQ). RESULTS: The radiographs of 661 patients (401
females; mean age 75.8+/-8.0) were evaluated. The inter-reader percent agreement
between two central expert radiologists per-vertebra assessment was excellent
(99.78%; k=0.984; 95% CI, 0.977-0.991). Central reading identified 318/661
(48.1%) patients with at least one VF. Local and central readings agreed in
502/661 (75.9%) patients, resulting in a fair reproducibility (k=0.52; 95%
confidence interval 0.44-0.59). Diagnostic performance parameters of local
readings were: sensitivity 76.1%; specificity 75.8%; PPV 74.46%; NPV 77.38%). By
examining 9254 vertebrae, central and local readers diagnosed 665 (7.2%) and 562
(6.1%) VFs respectively. Misdiagnosis (102 false positives and 205 false
negatives) mainly occurred for mild VFs. Local readings identified correctly 460
out 665 VFs diagnosed by central readings, resulting in sensitivity of 69.2% and
PPV of 81.8%. CONCLUSIONS: Following a standardized protocol of acquisition
techniques and of interpretation criteria, an excellent agreement between local
and central readings for moderate and severe vertebral fractures resulted.
However a significant amount of mild vertebral fractures, that are the most of
VFs, were misdiagnosed by local radiologists. In order to improve VFs assessment,
the radiologists should be trained and sensitized in relation to the relevant
clinical significance of osteoporotic VFs identification.
PMID- 28511875
TI - Visible light-switched cytosol release of siRNA by amphiphilic fullerene
derivative to enhance RNAi efficacy in vitro and in vivo.
AB - : Cationic macromolecules are attractive for use as small interfering RNA (siRNA)
carriers due to their performance in non-immunological reactions, customization
during synthesis, and low costs compared to viral carriers. However, their low
transfection efficiency substantially hinders their application in both clinical
practices and academic research, which is mostly attributable to the low capacity
of siRNA/cationic macromolecule complexes to escape lysosomes. To address this
challenge, we designed an amphiphilic fullerene derivative (C60-Dex-NH2) for
efficient and controllable siRNA delivery. To synthesize C60-Dex-NH2, terminally
aminated dextran was conjugated to C60. The conjugate was further cationized by
covalently introducing ethylenediamine to the dextran. The physicochemical
characteristics of C60-Dex-NH2 was examined with elemental analyses, gel
permeation chromatography, solid-state nuclear magnetic resonance (13C, HPDEC),
agarose gel electrophoresis, and dynamic light scattering. The cytotoxicity,
cellular uptake, intracellular distribution, and in vitro RNA interference (RNAi)
of siRNA/C60-Dex-NH2 complex was evaluated in the human breast cancer cell line
MDA-MB-231. The RNAi efficiencies mediated by C60-Dex-NH2in vivo was evaluated in
subcutaneous tumor-bearing mice. The results showed that C60-Dex-NH2 has a
specific amphiphilic skeleton and could form micelle-like aggregate structures in
water, which could prevent siRNA from destroying by reactive oxygen species
(ROS). When exposed to visible light, C60-Dex-NH2 could trigger controllable ROS
generation which could destroy the lysosome membrane, promote the lysosomal
escape, and enhance the gene silencing efficiency of siRNA in vitro and in vivo.
The gene silencing efficiency could reach a maximum of 53% in the MDA-MB-231-EGFP
cells and 69% in the 4T1-GFP-Luc2 tumor-bearing mice. STATEMENT OF SIGNIFICANCE:
We designed a novel photosensitive amphiphilic carrier (C60-Dex-NH2) for
efficient and controllable siRNA delivery, which can be used in gene therapy. We
showed that C60-Dex-NH2 could destroy lysosome membrane via controllable
generation of ROS when exposed to light, which can help siRNA to escape from
lysosome before degradation. This can enhance the gene silencing efficiency
significantly and provides a useful way to regulate RNAi efficiency by light. One
advantage for C60-Dex-NH2 system is C60 has broad absorbance spectrum and can be
activated by weak visible light; Furthermore, C60-Dex-NH2 has a specific
amphiphilic structure, which may prevent siRNA from degrading and allows C60-Dex
NH2 to embed into the lipid membrane of lysosome to improve the ROS induced
lysosomal disturbance after internalization.
PMID- 28511874
TI - Photothermal and photodynamic activity of polymeric nanoparticles based on alpha
tocopheryl succinate-RAFT block copolymers conjugated to IR-780.
AB - : The aim of this work was the generation of a multifunctional nanopolymeric
system that incorporates IR-780 dye, a near-infrared (NIR) imaging probe that
exhibits photothermal and photodynamic properties; and a derivate of alpha
tocopheryl succinate (alpha-TOS), a mitochondria-targeted anticancer compound. IR
780 was conjugated to the hydrophilic segment of copolymer PEG-b-polyMTOS, based
on poly(ethylene glycol) (PEG) and a methacrylic derivative of alpha-tocopheryl
succinate (MTOS), to generate IR-NP, self-assembled nanoparticles (NPs) in
aqueous media which exhibit a hydrophilic shell and a hydrophobic core. During
assembly, the hydrophobic core of IR-NP could encapsulate additional IR-780 to
generate derived subspecies carrying different amount of probe (IR-NP-eIR).
Evaluation of photo-inducible properties of IR-NP and IR-NP-eIR were thoroughly
assessed in vitro. Developed nanotheranostic particles showed distinct
fluorescence and photothermal behavior after excitation by a laser light emitting
at 808nm. Treatment of MDA-MB-453 cells with IR-NP or IR-NP-eIR resulted in an
efficient internalization of the IR-780 dye, while subsequent NIR-laser
irradiation led to a severe decrease in cell viability. Photocytoxicity conducted
by IR-NP, which could not be attributed to the generation of lethal hyperthermia,
responded to an increase in the levels of intracellular reactive oxygen species
(ROS). Therefore, the fluorescence imaging and inducible phototoxicity
capabilities of NPs derived from IR-780-PEG-b-polyMTOS copolymer confer high
value to these nanotheranostics tools in clinical cancer research. STATEMENT OF
SIGNIFICANCE: Multifunctional polymeric nanoparticles (NPs) that combine imaging
and therapeutic properties are highly valuable in cancer treatment. In this paper
we describe the development of NPs that are fluorescent in the near-infrared
(NIR). This is important for their visualization in living tissues that present
low absorption and low autofluorescence in this wavelength region (between 700
and 1000nm). Moreover, NPs present photothermal and photodynamic properties when
NIR irradiated: the NPs produce an efficient increment of temperature and
increase the intracellular reactive oxygen species (ROS) when laser irradiated at
808nm. These tuneable photoinduced properties make the NPs highly cytotoxic after
NIR irradiation and provide a new tool for highly precise cancer treatment.
PMID- 28511876
TI - Chondroitin sulfate-functionalized polyamidoamine as a tumor-targeted carrier for
miR-34a delivery.
AB - : Chondroitin sulfate (CS) was modified on a polyamidoamine dendrimer (PAMAM)
through Michael addition to construct a tumor-targeted carrier CS-PAMAM for miR
34a delivery. The derivative CS-PAMAM was demonstrated to achieve an efficient
cellular uptake of miR-34a in a CD44-dependent endocytosis way and further
facilitate the endosomal escape of miR-34a after 4h. Through the miR-34a
delivery, obvious inhibition of cell proliferation could be detected which was
attributed to the enhancement of cell apoptosis and cell cycle arrest, and
meanwhile the cell migration and invasion has been observed to be inhibited.
Finally, the intravenous injection of CS-PAMAM/miR-34a formulation into mice
bearing human lung adenocarcinoma cell A549 xenografts could efficiently inhibit
the tumor growth and induce the tumor apoptosis owing to the enhanced
accumulation of miR-34a in tumor tissue. Overall, CS-PAMAM is potential to be
used as a tumor-targeted oligonucleotide carrier for achieving tumor gene
therapy. STATEMENT OF SIGNIFICANCE: The cationic dendrimer PAMAM was modified by
chondroitin sulfate (CS) through Michael addition to construct a tumor-targeted
carrier CS-PAMAM for miR-34a delivery. The introduction of CS could achieve an
efficient cellular uptake and intracellular transfection of miR-34a in a CD44
dependent endocytosis manner. The miR-34a delivery could execute the anti
proliferation activity by simultaneously inducing cell apoptosis and cell cycle
arrest, and also the anti-migration activity. The CS-PAMAM-mediated systemic
delivery of miR-34a showed significant inhibition of tumor growth and induction
of tumor apoptosis using a mice model of subcutaneously implanted tumors.
PMID- 28511879
TI - [Pneumopericardium in a patient with lung carcinoma].
PMID- 28511878
TI - Epidemiological multicentre study on the education provided to patients with type
2 diabetes mellitus in the Spanish Health Care System. The Forma2 study.
AB - PURPOSE: The purpose of the present study was to characterize the education that
patients with type 2 diabetes mellitus receive, and to identify differences as
regards the presence of insulin therapy or not. METHODS: This crossover,
multicentre and descriptive study involved 1066 Spanish physicians who completed
a questionnaire on Internet. RESULTS: The physicians that responded had a mean of
26.0 years of experience in healthcare, and mainly worked in a walk-in clinic in
an urban area. Physicians rated the level of patient knowledge about their
disease on a 5.0 point-scale. Fifty percent of them indicated that they spent
between 15 and 30min in educating patients at the time of diagnosis. Previous
control with HbA1c>9%, presence of microvascular complications, and a low socio
cultural level, were factors associated with spending more time in education.
CONCLUSION: This is the first study designed to evaluate the education provided
to patients with type 2 diabetes mellitus from Spain. The time spent and the
individualization of the education are important factors associated with better
long-term control of the disease, and thus with the effectiveness of the clinical
management.
PMID- 28511877
TI - [Inflammatory injury on the chin].
PMID- 28511880
TI - [The tired adolescent: Evaluation and management in the family practice].
AB - The narrative review is used as a methodological tool for the presentation of
this article. A search was made in the PubMed, Elsevier, Ebsco, and Medline
databases using temporal limits (publications from 2005 to 2016), in the Spanish,
English, and Portuguese language, and by the type of persons analysed in the
study (adolescents), along with the keywords in English: Adolescent/teen,
tiredness, fatigue, sleepiness, drowsiness. A total of 33 articles of relevance
were obtained for the diagnostic and therapeutic approach of the tired adolescent
in Primary Care. It was found that the main cause of excessive daytime sleepiness
and drowsiness in adolescents is insufficient or inadequate sleep. For this
reason, a sleep assessment should be a routine component of the clinical
evaluation of adolescents, and as the initial approach to dismiss secondary
causes.
PMID- 28511881
TI - [What medication should be prescribed to a patient with coeliac disease?]
AB - Coeliac disease is a permanent intolerance to gluten proteins from wheat, rye,
barley and triticale. Although strict adherence is complicated, the only
effective treatment is a gluten-free diet throughout life. Some drugs contain
starch as an excipient, and there is a risk related to the gluten content, which
must be avoided in these patients. Current legislation requires the analysis of
the protein content of wheat starch, or the absence of starches from another
source where rice, maize, or potato starches are used as excipients. But, it does
not specify that reference should be made to traces of gluten that are residues
of the process of production of the active ingredient. As regards the case
described, there needs to be awareness of the importance of adequately informing
patients and reviewing/updating current legislation to ensure the safe use of
drugs.
PMID- 28511882
TI - [Warning of a resistant psoriasis; looking beyond the usual].
PMID- 28511884
TI - The Impact of Quality Variations on Patients Undergoing Surgery for Renal Cell
Carcinoma: A National Cancer Database Study.
AB - BACKGROUND: Despite efforts to define metrics assessing hospital-level quality
for renal cell carcinoma (RCC) surgical care there remains a paucity of real
world data validating their ability to benchmark performance. Consequently,
whether poor performance on hospital-level quality indicators is associated with
inferior patient outcomes remains unknown. OBJECTIVES: To determine hospital
level variations in RCC surgical quality after adjusting for differences in
patient- and tumor-specific factors. Further, to determine associations between
hospital-level quality performance and surgical volume, academic affiliation, and
patient mortality. DESIGN, SETTING, AND PARTICIPANTS: RCC patients undergoing
surgery in the USA and Puerto Rico (2004-2014) were identified from the National
Cancer Database. OUTCOME MEASURES AND STATISTICAL ANALYSIS: Hospital-level
quality of care was assessed according to disease-specific process and outcome
quality indicators. Case-mix adjusted hospital benchmarking was performed using
indirect standardization methodology and multivariable regression models. A
composite measure of quality, the Renal Cancer Quality Score (RC-QS), was
subsequently derived and associations between RC-QS and surgical volume, academic
affiliation, and patient mortality were determined. RESULTS AND LIMITATIONS: Over
1100 hospitals were benchmarked for quality, with 10-31% identified as providing
poor care for a given quality indicator. Lower RC-QS hospitals had smaller
referral volumes and were less academic compared with higher RC-QS hospitals
(p<0.001). Higher RC-QS was independently associated with lower 30-d, 90-d, and
overall mortality (adjusted odds ratio [confidence interval]: 0.92 [0.90-0.95],
odds ratio: 0.94 [0.91-0.96], hazard ratio: 0.97 [0.96-0.98] per unit increase,
respectively). These data are retrospective and it is unknown whether improvement
in the RC-QS improves outcomes. CONCLUSIONS: Widespread hospital-level variations
in RCC surgical quality exist, as captured by the RC-QS. Superior quality is
associated with improved patient outcomes, including mortality benefit. The RC-QS
serves as a benchmarking tool for RCC quality that can provide audit level
feedback to hospitals and policymakers for quality improvement. PATIENT SUMMARY:
We benchmarked hospital performance across quality indicators for kidney cancer
surgical care. Overall, large variations in quality exist, with high volume
academic hospitals demonstrating superior performance and improved patient
survival. These data can inform hospitals and policymakers for quality
improvement initiatives.
PMID- 28511885
TI - Salivary changes in type 2 diabetic patients.
AB - OBJECTIVE: this study was conducted to determine the effect of type 2 diabetes
mellitus on salivary secretion of glucose, amylase and immunoglobulin A levels
and also to fined out if saliva could be used as anon invasive method to monitor
glycaemic control in type 2 diabbetes. This study was conducted on 40 human
subjectes, They were 20 males and 20 females, their ages ranged from 35 years to
64 years,and they were divided into two groups, the first one is the patient
group which contains 20 diabetic paient. (10 males and 10 females,aged between 38
years to 64 years). the second one is the control group which contains 20 healthy
adult (10 males and 10 females,aged between 35 years to 60 years) they were age
and sex matched. All studied group were subjected to clinical and laboratory
investigation which includes post prandial blood glucose, HA1C, salivary glucose,
salivary amylase, and salivary immunoglobulin A. RESULTS: there was a highly
significant increase in the level of post prandial blood glucose, HBA1C; Salivary
glucose, Salivary amylase & Salivary immunoglobulin A in diabetic group compared
with control group and There was a significant positive correlation between post
prandial blood glucose and salivary glucose in diabetic group. CONCLUSIONS: These
results suggest that diabetes influences the composition of saliva and that
saliva can be used as less painful,non invasive biomarker for monitoring the
blood glucose concentration in the patients with diabetes mellitus.
PMID- 28511883
TI - A Prostate Cancer "Nimbosus": Genomic Instability and SChLAP1 Dysregulation
Underpin Aggression of Intraductal and Cribriform Subpathologies.
AB - BACKGROUND: Intraductal carcinoma (IDC) and cribriform architecture (CA)
represent unfavorable subpathologies in localized prostate cancer. We recently
showed that IDC shares a clonal ancestry with the adjacent glandular
adenocarcinoma. OBJECTIVE: We investigated for the co-occurrence of "aggression"
factors, genomic instability and hypoxia, and performed gene expression profiling
of these tumors. DESIGN, SETTING, AND PARTICIPANTS: A total of 1325 men were
treated for localized prostate cancer from four academic institutions (University
Health Network, CHU de Quebec-Universite Laval, Memorial Sloan Kettering Cancer
Center [MSKCC], and Erasmus Medical Center). Pathological specimens were
centrally reviewed. Gene copy number and expression, and intraprostatic
oxygenation were assessed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: IDC/CA
was separately assessed for biochemical relapse risk in the Canadian and MSKCC
cohorts. Both cohorts were pooled for analyses on metastasis. RESULTS AND
LIMITATION: Presence of IDC/CA independently predicted for increased risks of
biochemical relapse (HRCanadian 2.17, p<0.001; HRMSKCC 2.32, p=0.0035) and
metastasis (HRpooled 3.31, p<0.001). IDC/CA+ cancers were associated with an
increased percentage of genome alteration (PGA [median] 7.2 vs 3.0, p<0.001), and
hypoxia (64.0% vs 45.5%, p=0.17). Combinatorial genomic-pathological indices
offered the strongest discrimination for metastasis (C-index 0.805
[clinical+IDC/CA+PGA] vs 0.786 [clinical+IDC/CA] vs 0.761 [clinical]). Profiling
of mRNA abundance revealed that long noncoding RNA, SChLAP1, was the only gene
expressed at >3-fold higher (p<0.0001) in IDC/CA+ than in IDC/CA- tumors,
independently corroborated by increased SChLAP1 RNA in situ hybridization signal.
Optimal treatment intensification for IDC/CA+ prostate cancer requires
prospective testing. CONCLUSIONS: The poor outcome associated with IDC and CA
subpathologies is associated with a constellation of genomic instability, SChLAP1
expression, and hypoxia. We posit a novel concept in IDC/CA+ prostate cancer,
"nimbosus" (gathering of stormy clouds, Latin), which manifests as increased
metastatic capacity and lethality. PATIENT SUMMARY: A constellation of
unfavorable molecular characteristics co-occur with intraductal and cribriform
subpathologies in prostate cancer. Modern imaging for surveillance and treatment
intensification trials should be considered in this adverse subgroup.
PMID- 28511887
TI - Antioxidant polyphenols in cancer treatment: Friend, foe or foil?
AB - Cancer prevention can be probably obtained with easier, faster and less financial
strains by pursuing educational programs aimed to induce changes in lifestyle,
starting from dietary habits. In the past decades, observational and case-control
studies tried to establish a functional relationship between cancer mortality and
morbidity and diet. The field becomes even more intricate when scientists
investigated which dietary components are responsible for the putative,
protective effects of fruits and vegetables against cancer. A relevant part of
the literature focused on the positive role of "antioxidant" compounds in foods,
including polyphenols. The present review critically evaluate clinical and pre
clinical studies based on polyphenol administration, which contributed to support
the concept, deeply rooted in the general population, that antioxidant
polyphenols can fight cancer. The controversial and contradictory issues related
to the pros and cons on the use of polyphenols against cancer reflect the
confounding assumption that cancer treatment and cancer prevention may overlap.
We conclude that a clear cut must be done between these two concepts and that the
experimental approaches to investigate one or the other should be significantly
different, starting from adequate and specifically selected cellular models.
PMID- 28511889
TI - Severely infected pneumoceles of the frontal sinus in patients with mental
retardation and brain atrophy treated by endoscopic sinus surgery.
AB - We herein present three cases of abnormally expanded frontal sinuses
(pneumoceles) with severe infection in patients with mental retardation and brain
atrophy. Two patients previously underwent laryngotracheal separation surgery,
and bacteriological examinations of purulent nasal discharge revealed infections
caused by drug-resistant bacteria such as Pseudomonas aeruginosa and
Acinetobacter baumannii. As conservative medical treatments were ineffective, all
three patients were treated by computed tomography-guided endoscopic sinus
surgery. This navigation system is useful for safer surgery in the area of
anatomic deformity. The clinical findings, possible etiologies and surgical
treatment of these cases are discussed.
PMID- 28511888
TI - Simple visual review of pre- to post-operative renal ultrasound images predicts
pyeloplasty success equally as well as geometric measurements: A blinded
comparison with a gold standard.
AB - BACKGROUND: MAG3 diuretic renal scan remains the gold standard for determination
of improvement in renal drainage following pyeloplasty for ureteropelvic junction
obstruction. We hypothesized that (i) a change in geometric measurements between
pre-operative and post-operative renal ultrasound (RUS) images and (ii) blinded
simple visual review of images both would predict pyeloplasty success. OBJECTIVE:
To determine if simple visual review and/or novel geometric measurement of renal
ultrasounds can detect pyeloplasty failure. STUDY DESIGN: This study was a
retrospective, blinded comparison with a gold standard. Included were children
aged <=18 years undergoing pyeloplasty at our institution from 2009 to 2015. For
each kidney, representative pre-operative and post-operative RUS images were
chosen. Our standard for pyeloplasty success was improved drainage curve on MAG3
and lack of additional surgery. Measurements for collecting system circularity,
roundness, and renal parenchymal to collecting system area ratio (RPCSR) were
obtained by three raters (Figure), who were blinded to the outcome of the
pyeloplasty. Changes in geometric measurements were analyzed as a diagnostic test
for MAG3-defined pyeloplasty success using ROC curve analysis. In addition, six
reviewers blinded to pyeloplasty success reviewed pre-operative and post
operative images visually for improved hydronephrosis and categorized pyeloplasty
as success or failure based on simple visual review of RUS. RESULTS: Fifty-three
repaired renal units were identified (50 children). There were five pyeloplasty
failures, four of which underwent revision or nephrectomy. While all geometric
measurements could discriminate pyeloplasty failure and success, the geometric
measurements that discriminated best between pyeloplasty failure and success were
change in collecting system roundness and change in RPCSR. Consensus opinion
among six blinded reviewers using simple visual review had a sensitivity of 94%
and PPV of 100% with respect to identifying pyeloplasty success (AUC 0.97 (95% CI
0.93-1.0)). This was not significantly different from AUC for change in roundness
(p = 0.09) or change in RPCSR (p = 0.1). DISCUSSION: Change in collecting system
roundness and change in RPCSR were the most accurate geometric measurements in
predicting pyeloplasty success. Simple visual review of ultrasound images for
pyeloplasty success performed as well or better than geometric measurements.
However, geometric measurements remain useful as a research tool or to
communicate findings between clinicians. CONCLUSIONS: Complex geometric
measurements of hydronephrosis or post-operative MAG3 scans are not needed if
hydronephrosis is visually significantly improved, as simple visual review is
highly sensitive for detecting pyeloplasty failure.
PMID- 28511886
TI - Numtogenesis as a mechanism for development of cancer.
AB - Transfer of genetic material from cytoplasmic organelles to the nucleus, an
ongoing process, has implications in evolution, aging, and human pathologies such
as cancer. The transferred mitochondrial DNA (mtDNA) fragments in the nuclear
genome are called nuclear mtDNA or NUMTs. We have named the process numtogenesis,
defining the term as the transfer of mtDNA into the nuclear genome, or, less
specifically, the transfer of mitochondria or mitochondrial components into the
nucleus. There is increasing evidence of the involvement of NUMTs in human
biology and pathology. Although information pertaining to NUMTs and numtogenesis
is sparse, the role of this aspect of mitochondrial biology to human cancers is
apparent. In this review, we present available knowledge about the origin and
mechanisms of numtogenesis, with special emphasis on the role of NUMTs in human
malignancies. We describe studies undertaken in our laboratory and in others and
discuss the influence of NUMTs in tumor initiation and progression and in
survival of cancer patients. We describe suppressors of numtogenesis and
evolutionary conserved mechanisms underlying numtogenesis in cancer. An
understanding the emerging field of numtogenesis should allow comprehension of
this process in various malignancies and other diseases and, more generally, in
human health.
PMID- 28511890
TI - Intratympanic steroid delivery by an indwelling catheter in refractory severe
sudden sensorineural hearing loss.
AB - OBJECTIVE: Many studies over the last decade showed favorable outcomes with
intratympanic (IT) steroid treatment, alone as salvage treatment or in
combination with conventional systemic therapy (ST). However, in severe to
profound sensorineural hearing loss resistant to ST, the optimal infusion mode,
the type and concentration of the solution, the preferable drug, its total
amount, and the duration and fractionation of the treatment are still debated.
Aim of the study was to investigate the feasibility and the outcomes of a direct
and constant IT delivery of dexamethasone (DEX) by means of a new indwelling
catheter. METHODS: A prospective case-control study in a tertiary referral
university hospital. Ninety-nine subjects treated with ST only and 28 with
additional IT DEX have been included in the study. A 4 Fr catheter inserted in a
sub-annular fashion with a minimal postero-inferior tympanotomy through and
endocanalar approach under local anesthesia. DEX 4mg/ml delivered daily, up to 7
days. Daily bone and air-conducted pure tone and speech audiometry were performed
with a follow-up at 1, 3, 6 months after treatment. RESULTS: Twenty-one out of 28
patients (75%) refractory to ST gained on average 24.0dB+/-20.5dB HL after IT
DEX, compared to 35.4% (average 6.7dB+/-16.6dB HL) of those receiving only
medical ST (p<0.001). No significant side effects were noted. CONCLUSION: In
severe to profound sudden deafness refractory to conventional ST, the daily
perfusion of 4mg/ml DEX through an intratympanic catheter is an easy, well
accepted procedure that enables patients to receive a drug in the middle ear in a
repeatable or sustained form, with minimal discomfort and a partial rescue
(67.86%) and a speech recognition gain of 39%.
PMID- 28511891
TI - External pelvic and vaginal irradiation vs. vaginal irradiation alone as
postoperative therapy in women with early stage uterine serous carcinoma: Results
of a National Cancer Database analysis.
AB - PURPOSE: Adjuvant treatment in early stage uterine serous carcinoma (USC) usually
consists of chemotherapy with vaginal brachytherapy (VB), pelvic external beam
radiation therapy (EBRT), or combination. We compared survival outcomes across
these various radiation treatment modalities using the National Cancer Database.
METHODS AND MATERIALS: The National Cancer Database was queried for adult females
with histologically confirmed International Federation of Gynecology and
Obstetrics 1988 Stage I-II USC diagnosed from 2003 to 2013 treated definitively
with hysterectomy, adjuvant chemotherapy, and radiation therapy. chi2 tests were
used to assess differences by radiation type (VB, pelvic EBRT, and EBRT + VB) and
various clinical variables. Kaplan-Meier and log-rank test methods were used to
evaluate survival outcomes. Risk factors related to overall survival were
identified by univariate and multivariate analysis. RESULTS: We identified 1336
patients with USC who met our inclusion criteria. Most patients were treated with
VB (66%) compared with EBRT (21%) or combination EBRT + VB (13%). The proportion
of patients who received EBRT (including EBRT + VB) was higher for those who did
not have a lymph node dissection or with fewer dissected lymph nodes. Patients
treated with VB alone had longer 5-year survival rates (84% [95% confidence
interval: 80, 90]) than those treated with EBRT (75% [95% confidence interval:
69, 80]) (p < 0.001). On multivariate analysis, the presence of lymphovascular
space invasion (hazard ratio, 2.48; p < 0.001) and the absence of a lymph node
dissection (hazard ratio, 2.24; p = 0.047) were independent predictors of overall
survival. CONCLUSIONS: This large hospital-based study suggests that VB alone may
be sufficient for adjuvant radiation treatment in women with USC treated with
adjuvant chemotherapy and who underwent an adequate surgical staging.
PMID- 28511892
TI - Occurrence and biosynthesis of carotenoids in phytoplankton.
AB - Naturally occurring carotenoids are important sources of antioxidants, anti
cancer compounds and anti-inflammatory agents and there is thus considerable
market demand for their pharmaceutical applications. Carotenoids are widely
distributed in marine and freshwater organisms including microalgae,
phytoplankton, crustaceans and fish, as well as in terrestrial plants and birds.
Recently, phytoplankton-derived carotenoids have received much attention due to
their abundance, rapid rate of biosynthesis and unique composition. The
carotenoids that accumulate in particular phytoplankton phyla are synthesized by
specific enzymes and play unique physiological roles. This review focuses on
studies related to the occurrence of carotenoids in different phytoplankton phyla
and the molecular aspects of their biosynthesis. Recent biotechnological advances
in the isolation and characterization of some representative carotenoid synthases
in phytoplankton are also discussed.
PMID- 28511893
TI - Assessment of the effectiveness of attenuation of Pb aprons by using TLD
dosimetry and Monte Carlo calculations.
AB - We developed an experimental set-up by using a continuous emission X-ray (Pantak
DXT-3000) and three types of Pb aprons, with thicknesses of 0.25, 0.5, and
0.75mm, coated with Mylar fiber on their surface. Aprons were placed at a
distance of 2.5m from the focus. Aluminum filtration was performed at the beam
output to reproduce the qualities of narrow beams, N40 (Eeffective =33keV), N80
(Eeffective =65keV), and N100 (Eeffective =83keV), according to the ISO standard
4037 (1-3). Each apron was fixed with 10 thermoluminescent dosimeters (TLDs) over
its surface, five dosimeters before and five dosimeters after irradiation with X
rays. Dosimeter readings were noted, and the attenuation coefficients for each
effective energy were calculated. To confirm the method of effective energy of
ISO-4037 and evaluate the effectiveness of aprons according to the energy range
required for different medical practices, a Monte Carlo simulation using GEANT4
code was performed. Thus, the fluence and the absorbed dose in each of the
dosimeters were determined, and then the coefficients of linear attenuation were
calculated and compared with the experimental data and with those reported by the
National Institute of Standards and Technology. Results were consistent between
theoretical calculations and experimental measures. This work will serve to make
assessments for other personalized radiation protectors made of Pb.
PMID- 28511894
TI - Incorporating simulation into gynecologic surgical training.
AB - Today's educational environment has made it more difficult to rely on the
Halstedian model of "see one, do one, teach one" in gynecologic surgical
training. There is decreased surgical volume, but an increased number of surgical
modalities. Fortunately, surgical simulation has evolved to fill the educational
void. Whether it is through skill generalization or skill transfer, surgical
simulation has shifted learning from the operating room back to the classroom.
This article explores the principles of surgical education and ways to introduce
simulation as an adjunct to residency training. We review high- and low-fidelity
surgical simulators, discuss the progression of surgical skills, and provide
options for skills competency assessment. Time and money are major hurdles when
designing a simulation curriculum, but low-fidelity models, intradepartmental
cost sharing, and utilizing local experts for simulation proctoring can aid in
developing a simulation program.
PMID- 28511896
TI - [Changes in the prevalence of statin use in Germany - findings from national
health interview and examination surveys 1997-1999 and 2008-2011].
AB - BACKGROUND: Evidence-based guideline recommendations on lipid lowering drug
treatment, in particular statin treatment, play an essential role in the
management of dyslipidemias and in the prevention of cardiovascular disease
events. In Germany, statutory health insurance data provide information on time
trends in the prescription of lipid lowering drugs. However, population-based
data regarding changes in user prevalence according to socio-demographic and
health-related characteristics are lacking. Based on data from national health
interview and examination surveys for adults in Germany 1997-1999 (GNHIES98) and
2008-2010 (DEGS1), the present analysis aims to close this information gap with a
particular focus on the use of statins. METHODS: The study population consisted
of 7,099 participants (GNHIES98) and 7,091 participants (DEGS1) aged 18 to 79
years at the time of the respective surveys. Primary data on medication use
within 7 days prior to the survey were collected using standardized medication
interviews and brown-bag drug review. Unique product identifiers on original drug
containers were scanned and coded according to the latest version of the
Anatomical Therapeutic Chemical (ATC) classification system. Medical history was
obtained in computer-assisted personal interviews. A history of stroke or
coronary heart disease (CHD) was assessed among persons aged 40 to 79 years only,
and previous stroke or CHD were defined as cardiovascular disease. Obesity was
defined as a body mass index (BMI) of >= 30kg/m2) based on calculation from
standardized measures of body weight and height. Information on socio-demographic
variables and type of health insurance was collected using standardized self
administered questionnaires. In cross-sectional descriptive analyses we
calculated the prevalence of statin use (ATC codes: C10AA, C10BA, C10BX) by
survey as well as the changes between surveys stratified according to relevant
preexisting diseases and other co-variables. The association between survey
period and statin use was analyzed in multivariable binary logistic regression
models among persons aged 40 to 79 years. All results were weighted and
standardized for the population of 2010. RESULTS: Between the two survey periods
1997-1999 and 2008-2011, the prevalence of statin use increased from 3.2 % to 8.8
%. The increase was most pronounced for the age group 65 to 79 years (7.2 % vs.
26.9 %) and among persons with relevant preexisting conditions, such as CHD (19.1
% vs. 54.9 %), stroke (17.1 % vs. 50.1 %), diabetes mellitus (10.5 % vs. 33.2 %),
and dyslipidemia (12.6 % vs. 27.8 %). Among persons aged 40 to 79 years, the
prevalence of statin use significantly increased between the two surveys,
independent of co-variables (Odds Ratio: 3.70; 95 % confidence interval [CI]:
2.92 to 4.70). This applied to persons with cardiovascular disease (5.17; 3.50 to
7.64) and without cardiovascular disease (2.76; 2.07 to 3.67). CONCLUSION: The
increase in the prevalence of statin use in Germany between the two national
health surveys (1997-1999 and 2008-2011) reflects the implementation of current
guideline recommendations without evidence for inequalities according to gender,
education, type of health insurance or region of residence. These population
based data add to information on statin prescription obtained from statutory
health insurance data. Limitations of survey-based information derive from
potential misclassification and selection bias as well as large time gaps between
the survey periods. Further studies are needed to examine why the observed
prevalence of statin use among persons with cardiovascular morbidity lags behind
current guideline recommendations for secondary cardiovascular prevention.
PMID- 28511897
TI - Takotsubo in amyotrophic lateral sclerosis.
PMID- 28511898
TI - Is the Takotsubo syndrome a brain-heart or multiorgan disorder?
PMID- 28511895
TI - Diagnostic performance of Anyplex II MTB/MDR/XDR for detection of resistance to
first and second line drugs in Mycobacterium tuberculosis.
AB - PURPOSE: Genotypic methods have considerably improved the diagnosis of multidrug
resistant (MDR) tuberculosis. One of these tests is Anyplex II MTB/MDR/XDR
(Anyplex). Our aim was to evaluate the diagnostic performance of this multiplex
PCR. METHODS: We conducted our study on 47 MDR tuberculosis and 14 pan
susceptible strains. We evaluated the ability of Anyplex to detect resistance
mutations in rpoB (rifampin [RIF]), katG and inhA (isoniazid [INH]), gyrA
(fluoroquinolones [FLQ]), and rrs and eis (aminoglycosides [AMG]). We used the
agar proportion method as gold standard. We also studied concordance with
GenoType MTBDRplus (first line drugs) and MTBDRsl (second line drugs). DNA
sequencing was applied to clarify discrepancies. RESULTS: All pan-susceptible
strains were susceptible by Anyplex. Sensitivity and specificity of Anyplex for
detection of resistance mutations were 97.9% and 100%, respectively, for RIF,
91.5% and 100% for INH, 80% and 100% for FLQ, and 50% and 99.7% for AMG.
Concordance with GenoType was perfect for RIF, INH, and FLQ (kappa score, k=1.0)
and moderate for AMG (k=0.48). Sensitivity and specificity for detection of MDR
tuberculosis were 89.4% and 100%, respectively. DNA sequencing of the
phenotypically resistant strains considered as susceptible by Anyplex, confirmed
no mutations in the corresponding genes. CONCLUSIONS: Anyplex is a reliable assay
for the detection of MDR tuberculosis and shows excellent concordance with
GenoType. Anyplex reduces the time to diagnosis of MDR tuberculosis strains, as
it is recommended by current guidelines on control of tuberculosis.
PMID- 28511899
TI - Signaling pathways to and from the hypophysial pars tuberalis, an important
center for the control of seasonal rhythms.
AB - Seasonal (circannual) rhythms play an important role for the control of body
functions (reproduction, metabolism, immune responses) in nearly all living
organisms. Also humans are affected by the seasons with regard to immune
responses and mental functions, the seasonal affective disorder being one of the
most prominent examples. The hypophysial pars tuberalis (PT), an important
interface between the hypophysial pars distalis and neuroendocrine centers in the
brain, plays an essential role in the regulation of seasonal functions and may
even be the seat of the circannual clock. Photoperiodic signals provide a major
input to the PT. While the perception of these signals involves extraocular
photoreceptors in non-mammalian species (birds, fish), mammals perceive
photoperiodic signals exclusively in the retina. A multisynaptic pathway connects
the retina with the pineal organ where photoperiodic signals are translated into
the neurohormone melatonin that is rhythmically produced night by night and
encodes the length of the night. Melatonin controls the functional activity of
the mammalian PT by acting upon MT1 melatonin receptors. The PT sends its output
signals via retrograde and anterograde pathways. The retrograde pathway
targetting the hypothalamus employs TSH as messenger and controls a local
hypothalamic T3 system. As discovered in Japanese quail, TSH triggers molecular
cascades mediating thyroid hormone conversion in the ependymal cell layer of the
infundibular recess of the third ventricle. The local accumulation of T3 in the
mediobasal hypothalamus (MBH) appears to activate the gonadal axis by affecting
the neuro-glial interaction between GnRH terminals and tanycytes in the median
eminence. This retrograde pathway is conserved in photoperiodic mammals (sheep
and hamsters), and even in non-photoperiodic laboratory mice provided that they
are capable to synthesize melatonin. The anterograde pathway is implicated in the
control of prolactin secretion, targets cells in the PD and supposedly employs
small molecules as signal substances collectively denominated as "tuberalins".
Several "tuberalin" candidates have been proposed, such as tachykinins, the
secretory protein TAFA and endocannabinoids (EC). The PT-intrinsic EC system was
first demonstrated in Syrian hamsters and shown to respond to photoperiodic
changes. Subsequently, the EC system was also demonstrated in the PT of mice,
rats and humans. To date, 2-arachidonoylglycerol (2-AG) appears as the most
important endocannabinoid from the PT. Likely targets for the EC are folliculo
stellate cells that contain the CB1 receptor and appear to contact lactotroph
cells. The CB1 receptor was also found on corticotroph cells which appear as a
further target of the EC. Recently, the CB1 receptor was also localized to CRF
containing nerve fibers running in the outer zone of the median eminence. This
finding suggests that the EC system of the PT contributes not only to the
anterograde, but also to the retrograde pathway. Taken together, the results
support the concept that the PT transmits its signals via a "cocktail" of
messenger molecules which operate also in other brain areas and systems rather
than through PT-specific "tuberalins". Furthermore, they may attribute a novel
function to the PT, namely the modulation of the stress response and immune
functions.
PMID- 28511900
TI - Predictive value of CT for first esophageal variceal bleeding in patients with
cirrhosis: Score calibration and prediction.
PMID- 28511901
TI - First haplosporidan parasite reported infecting a member of the Superfamily
Pinnoidea (Pinna nobilis) during a mortality event in Alicante (Spain, Western
Mediterranean).
AB - Several stages of a haplosporidan parasite, including spores, were detected
infecting three out of four specimens of the Pen Shell Pinna nobilis from the
coast of Alicante (Western Mediterranean). A mortality event initiated few weeks
before the sampling. The infection was systemic in the connective tissue, with
free uni-nucleate stages and early plasmodia, whereas sporulation process took
place in the digestive tubules disrupting them. Morphological details, by light
and transmission electron microscopy, and PCR amplification confirmed that the
parasite belongs to the haplosporidan group. Spores were pleomorphic, usually
elongated ovoid, with round to elongated haplosporosomes-like in the sporoplasma.
The operculum was situated in the apical zone of the wall, with an external lid,
and the nucleus tended to be eccentric in the basal zone. Spore ornamentation was
not observed. The single uninfected specimen appeared to be healthy. This is the
first report of a haplosporidan parasite infecting a member of the Superfamily
Pinnoidea and this is the first histopathological study of a mortality event in
the endangered and protected P. nobilis.
PMID- 28511902
TI - Adiposity as a full mediator of the influence of cardiorespiratory fitness and
inflammation in schoolchildren: The FUPRECOL Study.
AB - BACKGROUND AND AIMS: Studies in the paediatric population have shown inconsistent
associations between cardiorespiratory fitness and inflammation independently of
adiposity. The purpose of this study was (i) to analyse the combined association
of cardiorespiratory fitness and adiposity with high-sensitivity C-reactive
protein (hs-CRP), and (ii) to determine whether adiposity acts as a mediator on
the association between cardiorespiratory fitness and hs-CRP in children and
adolescents. METHODS AND RESULTS: This cross-sectional study included 935 (54.7%
girls) healthy children and adolescents from Bogota, Colombia. The 20 m shuttle
run test was used to estimate cardiorespiratory fitness. We assessed the
following adiposity parameters: body mass index, waist circumference, and fat
mass index and the sum of subscapular and triceps skinfold thickness. High
sensitivity assays were used to obtain hs-CRP. Linear regression models were
fitted for mediation analyses examined whether the association between
cardiorespiratory fitness and hs-CRP was mediated by each of adiposity parameters
according to Baron and Kenny procedures. Lower levels of hs-CRP were associated
with the best schoolchildren profiles (high cardiorespiratory fitness + low
adiposity) (p for trend <0.001 in the four adiposity parameters), compared with
unfit and overweight (low cardiorespiratory fitness + high adiposity)
counterparts. Linear regression models suggest a full mediation of adiposity on
the association between cardiorespiratory fitness and hs-CRP levels. CONCLUSIONS:
Our findings seem to emphasize the importance of obesity prevention in childhood,
suggesting that having high levels of cardiorespiratory fitness may not
counteract the negative consequences ascribed to adiposity on hs-CRP.
PMID- 28511903
TI - Novel role of the nutraceutical bioactive compound berberine in lectin-like OxLDL
receptor 1-mediated endothelial dysfunction in comparison to lovastatin.
AB - BACKGROUND AND AIMS: Oxidized LDL (oxLDL) or pro-inflammatory stimuli lead to
increased oxidative stress linked to endothelial dysfunction and atherosclerosis.
The oxLDL receptor-1 (LOX1) is elevated within atheromas and cholesterol-lowering
statins inhibit LOX1 expression. Berberine (BBR), an alkaloid extracted from
plants of gender Berberis, has lipid-lowering and anti-inflammatory activity.
However, its role in regulating LOX1-mediated signaling is still unknown. The aim
of this study was to investigate the effect of BBR on oxLDL- and TNFalpha-induced
endothelial dysfunction in human umbilical vein endothelial cells (HUVECs) and to
compare it with that of lovastatin (LOVA). METHODS AND RESULTS: Cytotoxicity was
determined by lactate dehydrogenase assay. Antioxidant capacity was measured with
chemiluminescent and fluorescent method and intracellular ROS levels through a
fluorescent dye. Gene and protein expression levels were assayed by qRT-PCR and
western blot, respectively. HUVECs exposure to oxLDL (30 MUg/ml) or TNFalpha (10
ng/ml) for 24 h led to a significant increase in LOX1 expression, effect
abrogated by BBR (5 MUM) and LOVA (5 MUM). BBR but not LOVA treatment abolished
the TNFalpha-induced cytotoxicity and restored the activation of Akt signaling.
In spite of a low direct antioxidant capacity, both compounds reduced
intracellular ROS levels generated by treatment of TNFalpha but only BBR
inhibited NOX2 expression, MAPK/Erk1/2 signaling and subsequent NF-kappaB target
genes VCAM and ICAM expression, induced by TNFalpha. CONCLUSIONS: These findings
demonstrated for the first time that BBR could prevent the oxLDL and TNFalpha -
induced LOX1 expression and oxidative stress, key events that lead to NOX,
MAPK/Erk1/2 and NF-kappaB activation linked to endothelial dysfunction. CHEMICAL
COMPOUNDS STUDIED IN THIS ARTICLE: Berberine (PubChem CID: 2353); Lovastatin
(PubChem CID: 53232).
PMID- 28511904
TI - Analysis of the association of leptin and adiponectin concentrations with
metabolic syndrome in children: Results from the IDEFICS study.
AB - BACKGROUND AND AIMS: Adipokines may play a role in the pathogenesis of the
metabolic syndrome (MetS) in children. We aimed to evaluate the association of
leptin, adiponectin, and its ratio (L/A ratio) with the metabolic syndrome (MetS)
in a subsample of the IDEFICS (Identification and prevention of Dietary- and
lifestyle-induced health EFfects In Children and infantS) cohort. METHODS AND
RESULTS: Leptin, adiponectin and MetS parameters were measured in a subsample of
1253 children (3-9.9 years) participating to the IDEFICS study, grouped as: Non
OW (underweight/normal weight) and OW/Ob (overweight/obese). MetS was defined
using the sex- and age-specific cut-offs based on the distribution of MetS
components in the IDEFICS cohort. The prevalence of the MetS among OW/Ob was
24.8% and 27.1% in boys and girls respectively, whereas <=2% among Non-OW. OW/Ob
had significantly higher leptin and L/A ratio as compared to Non-OW.
Significantly higher leptin was found in OW/Ob with MetS as compared with OW/Ob
without MetS. Significantly lower adiponectin was observed only in OW/Ob girls as
compared to Non-OW. A 1SD increase in leptin and L/A ratio z-scores or a 1SD
decrease in adiponectin z-score were significantly associated with higher risk of
MetS. After adjustment for BMI or body fat mass (BFM) the association remained
significant only for leptin. CONCLUSION: We showed that in European children,
higher leptin concentration is associated with MetS, even after adjusting for BMI
or BFM, confirming an early role of leptin in MetS, while the association of
adiponectin with MetS seems be mediated by body fat in this age range.
PMID- 28511905
TI - Hemorheological alterations in adults with prediabetes identified by hemoglobin
A1c levels.
AB - BACKGROUND AND AIMS: A link between increased blood viscosity and type 2 diabetes
has been previously reported. Herein, we investigated the association of blood
viscosity with prediabetes, identified by glycated hemoglobin A1c (HbA1c)
according to the new American Diabetes Association criteria, and subclinical
atherosclerosis. METHODS AND RESULTS: The study cohort includes 1136 non-diabetic
adults submitted to anthropometrical evaluation, an oral glucose tolerance test
and ultrasound measurement of carotid intima-media thickness (IMT). Whole blood
viscosity was estimated using a validated formula based on hematocrit and total
plasma proteins. After adjusting for age, and gender, individuals with HbA1c
defined prediabetes (HbA1c 5.7-6.4% [39-47 mmol/mol]) exhibited significantly
higher values of hematocrit, and predicted blood viscosity as compared with
controls. Increased levels of IMT were observed in subjects with HbA1c-defined
prediabetes in comparison to controls. Predicted blood viscosity was positively
correlated with age, waist circumference, blood pressure, cholesterol,
triglycerides, fibrinogen, white blood cell, HbA1c, fasting and 2-h post-load
glucose levels, fasting insulin, IMT and inversely correlated with HDL and
Matsuda index of insulin sensitivity. Of the three glycemic parameters, i.e.
HbA1c, fasting and 2-h post-load glucose, only HbA1c showed a significant
correlation with predicted blood viscosity (beta = 0.054, P = 0.04) in a
multivariate regression analysis model including multiple atherosclerosis risk
factors. CONCLUSION: The study shows that individuals with HbA1c-defined
prediabetes have increased predicted blood viscosity and IMT. The HbA1c criterion
may be helpful to capture individuals with an increased risk of diabetes and
cardiovascular disease who may benefit from an intensive lifestyle intervention.
PMID- 28511906
TI - Design, synthesis and anti-tumor activity study of novel histone deacetylase
inhibitors containing isatin-based caps and o-phenylenediamine-based zinc binding
groups.
AB - As a hot topic of epigenetic studies, histone deacetylases (HDACs) are related to
lots of diseases, especially cancer. Further researches indicated that different
HDAC isoforms played various roles in a wide range of tumor types. Herein a novel
series of HDAC inhibitors with isatin-based caps and o-phenylenediamine-based
zinc binding groups have been designed and synthesized through scaffold hopping
strategy. Among these compounds, the most potent compound 9n exhibited similar if
not better HDAC inhibition and antiproliferative activities against multiple
tumor cell lines compared with the positive control entinostat (MS-275).
Additionally, compared with MS-275 (IC50 values for HDAC1, 2 and 3 were 0.163,
0.396 and 0.605uM, respectively), compound 9n with IC50 values of 0.032, 0.256
and 0.311uM for HDAC1, 2 and 3 respectively, showed a moderate HDAC1 selectivity.
PMID- 28511907
TI - Potential inhibitors of human carbonic anhydrase isozymes I and II: Design,
synthesis and docking studies of new 1,3,4-thiadiazole derivatives.
AB - In the last years, inhibition of carbonic anhydrase (CA) has emerged as a
promising approach for pharmacologic intervention in a variety of disorders such
as glaucoma, epilepsy, obesity, and cancer. As a consequence, the design of CA
inhibitors (CAIs) is a highly dynamic field of medicinal chemistry. Due to the
therapeutic potential of thiadiazoles as CAIs, new 1,3,4-thiadiazole derivatives
were synthesized and investigated for their inhibitory effects on hCA I and hCA
II. Although the tested compounds did not carry a sulfonamide group, an important
pharmacophore for CA inhibitory activity, it was a remarkable finding that most
of them were more effective on hCAs than acetazolamide (AAZ), the reference
agent. Among these compounds, N'-((5-(4-chlorophenyl)furan-2-yl)methylene)-2-((5
(phenylamino)-1,3,4-thiadiazol-2-yl)thio)acetohydrazide (3) was found to be the
most effective compound on hCA I with an IC50 value of 0.14nM, whereas N'-((5-(2
chlorophenyl)furan-2-yl)methylene)-2-((5-(phenylamino)-1,3,4-thiadiazol-2
yl)thio)acetohydrazide (1) was found to be the most potent compound on hCA II
with an IC50 value of 0.15nM. According to molecular docking studies, all
compounds exhibited high affinity and good amino acid interactions similar to AAZ
on the both active sites of hCA I and hCA II enzymes.
PMID- 28511908
TI - Potential anti-gout constituents as xanthine oxidase inhibitor from the fruits of
Stauntonia brachyanthera.
AB - With the aim of finding a better xanthine oxidase inhibitor with potential anti
gout properties, the studies on the fruit of Stauntonia brachyanthera were
carried out, which led to the isolation of 12 glycosides, including 4 new nor
oleanane triterpenoids. Their structures were determined by comprehensive
spectroscopic (NMR and HR MS) analysis. Two compounds (4 and 11) exhibited
significant inhibitory activities on xanthine oxidase with IC50 values of 5.22
and 1.60uM, respectively. Another five compounds (1, 2, 3, 8 and 10) showed
qualified activities. The results suggested that the existences of nor-oleanane
triterpenoids and flavonoids in the fruits were responsible for the inhibitory
activity on xanthine oxidase that could cut off the production of uric acid. Nor
oleanane triterpenoids, a new leading XO inhibitor, is worthy of further studies
on molecular biology level for its mechanisms.
PMID- 28511909
TI - Discovery and structure-guided fragment-linking of 4-(2,3-dichlorobenzoyl)-1
methyl-pyrrole-2-carboxamide as a pyruvate kinase M2 activator.
AB - Tumor cells switch glucose metabolism to aerobic glycolysis by expressing the
pyruvate kinase M2 isoform (PKM2) in a low active form, providing glycolytic
intermediates as building blocks for biosynthetic processes, and thereby
supporting cell proliferation. Activation of PKM2 should invert aerobic
glycolysis to an oxidative metabolism and prevent cancer growth. Thus, PKM2 has
gained attention as a promising cancer therapy target. To obtain novel PKM2
activators, we conducted a high-throughput screening (HTS). Among several hit
compounds, a fragment-like hit compound with low potency but high ligand
efficiency was identified. Two molecules of the hit compound bound at one
activator binding site, and the molecules were linked based on the crystal
structure. Since this linkage succeeded in maintaining the original position of
the hit compound, the obtained compound exhibited highly improved potency in an
in vitro assay. The linked compound also showed PKM2 activating activity in a
cell based assay, and cellular growth inhibition of the A549 cancer cell line.
Discovery of this novel scaffold and binding mode of the linked compound provides
a valuable platform for the structure-guided design of PKM2 activators.
PMID- 28511910
TI - Synthesis and biological research of novel azaacridine derivatives as potent DNA
binding ligands and topoisomerase II inhibitors.
AB - DNA and DNA-related enzymes are one of the most effective and common used
intracellular anticancer targets in clinic and laboratory studies, however, most
of DNA-targeting drugs suffered from toxic side effects. Development of new
molecules with good antitumor activity and low side effects is important. Based
on computer aided design and our previous studies, a series of novel azaacridine
derivatives were synthesized as DNA and topoisomerases binding agents, among
which compound 9 displayed the best antiproliferative activity with an IC50 value
of 0.57MUM against U937 cells, which was slightly better than m-AMSA. In
addition, compound 9 displayed low cytotoxicity against human normal liver cells
(QSG-7701), the IC50 of which was more than 3 times lower than m-AMSA. Later
study indicated that all the compounds displayed topoisomerases II inhibition
activity at 50MUM. The representative compound 9 could bind with DNA and induce
U937 apoptosis through the exogenous pathway.
PMID- 28511911
TI - Sulfonamide inhibition profiles of the beta-carbonic anhydrase from the
pathogenic bacterium Francisella tularensis responsible of the febrile illness
tularemia.
AB - A new beta-class carbonic anhydrase (CA, EC 4.2.1.1) has been cloned, purified
and characterized in the genome of the pathogenic bacterium Francisella
tularensis responsible of the febrile illness tularemia. This enzyme, FtubetaCA,
showed a kcat of 9.8 *105s-1 and a kcat/KM of 8.9 *107M-1s-1 for the CO2
hydration, physiological reaction, being one of the most effective beta-CAs known
to date, with a catalytic activity only 1.68-times lower than that of the
human(h) isoform hCA II. A panel of 39 simple aromatic and heterocyclic
sulfonamides, as well as clinically used drugs incorporating
sulfonamide/sulfamate zinc-binding groups, was used to investigate the inhibition
profile of FtubetaCA with these classes of derivatives. The enzyme generally
showed a weaker affinity for these inhibitors compared to other alpha- and beta
CAs investigated earlier, with only acetazolamide and its deacetylated precursor
having inhibition constant <1uM. Indeed, the two compounds acetazolamide AAZ and
its deacetylated precursor 13 (KIs of 655-770nM), as well as metanilamide and
methazolamide (KIs of 2.53-2.92uM), were the best FtubetaCA inhibitors detected
so far. As the physiological role of bacterial beta-CAs is poorly understood for
the virulence/life cycle of these pathogens, the present study may constitute a
starting point for the design of effective pathogenic bacteria CA inhibitors with
potential use as antiinfectives.
PMID- 28511912
TI - Inhibition of KDM4A activity as a strategy to suppress interleukin-6 production
and attenuate colitis induction.
AB - 4-Chloro-7-nitro-2,1,3-benzoxadiazole (NBD-Cl) functions as a hapten and
fluoresces upon binding to proteins. Therefore, fluorescence visualization of
hapten-proteins is a feature of the colitis induced by NBD-Cl. Using this colitis
model, we located activated fibroblasts in the vicinity of hapten-proteins upon
colitis induction and observed interleukin (IL)-6 production in the activated
fibroblasts. We screened herbal ingredients using primary fibroblasts stimulated
with tumor necrosis factor alpha (TNF-alpha) and found the suppressive action of
Atractylodin on IL-6 production. Under TNF-alpha stimulation, Atractylodin
induced the tri-methylation of histone H3 at lysine residue 9, which impaired the
binding between NF-kappaB and the IL-6 promoter on the genomic DNA. Atractylodin
inhibited KDM4A but not KDM6A activity. Atractylodin administration attenuated
colitis induction. The KDM4A inhibitor ML324 showed similar actions on IL-6
production and colitis induction. We propose the inhibition of KDM4A activity as
a strategy to suppress IL-6 production and attenuate colitis induction.
PMID- 28511913
TI - The non-peptide CRH1-antagonist CP-154,526 elicits a paradoxical route-dependent
activation of the HPA axis.
AB - The corticotropin-releasing hormone (CRH) plays an important role in mediating
physiological response to stress and is thought to be involved in the development
of various psychiatric disorders. In this paper, we compare the differences
between the effect of intraperitoneal (i.p.) and intraarterial (i.a.)
administration of the non-peptide CRH1 antagonist CP-154,526 (CP) (10 and
20mg/kg) on plasma adrenocorticotropic hormone levels (ACTH), heart rate, MAP,
and c-Fos expression in the paraventricular nucleus of the hypothalamus.
Intraperitoneal, but not i.a., injection of CP resulted in an increase in plasma
ACTH (from 105+/-13 to 278+/-51pg/ml after 20mg/kg). This effect was accompanied
by a dramatic increase in c-Fos expression in cells immunoreactive for CRH in the
paraventricular nucleus of the hypothalamus. When the drug was administered i.p.,
CP-induced activation of the HPA appears to mask the inhibitory effect of CP on
stress-induced ACTH secretion, an effect which was readily apparent when the drug
was given i.a. Intraperitoneal administration of CP also increased the baseline
MAP which may account for previous reports that treatment with this drug
attenuated the increases associated with stress. CP given by either route had no
effect on baseline heart rate or stress-induced tachycardia. Thus, in all studies
in which CP 154,526 is given, the route of delivery must be given careful
consideration.
PMID- 28511914
TI - Digitoxin increases sensitivity of glioma stem cells to TRAIL-mediated apoptosis.
AB - Malignant glioma is one type of common malignancy in central nervous system (CNS)
tumors which has a very bad influence on the survival quality of the patients. In
this regard, lots of studies on improving the therapeutic effects of malignant
glioma have been done continuously. This study takes glioma stem cells (GSCs) as
the subject and focuses on the sensitization effect of digitoxin (DT) on the
apoptosis mediated by TNF-related apoptosis-inducing ligand (TRAIL) to prove that
the combination therapy of DT and TRAIL has a more active effect of inducing GSCs
apoptosis. This study used cultured GSCs. Comparisons of single drug therapy and
combination therapy indicated that DT had a synergistic action with TRAIL to
produce a more active effect of inducing the apoptosis of GSCs. This effect was
also shown in the changes of expressions of cell apoptosis pathway related
protein markers tested by Western Blot method. In conclusion, DT had a
sensitization effect on GSCs apoptosis mediated by TRAIL.
PMID- 28511915
TI - Altered ionic currents and amelioration by IGF-1 and PACAP in motoneuron-derived
cells modelling SBMA.
AB - Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is a
motor neuron disease caused by the expansion of a polymorphic CAG tandem repeat
encoding a polyglutamine (polyQ) tract in the androgen receptor (AR) gene. SBMA
is triggered by the binding of mutant AR to its natural ligands, testosterone and
dihydrotestosterone (DHT). To investigate the neuronal alterations of motor
neuron cell models of SBMA, we applied patch-clamp methods to verify how polyQ
expansions in the AR alter cell ionic currents. We used mouse motoneuron-derived
MN-1 cells expressing normal AR (MN24Q) and mutant AR (MN100Q treated cells with
vehicle EtOH and DHT). We observed a reduction of the current flux mainly at
depolarizing potentials in the DHT-treated cells, while the dissection of
macroscopic currents showed single different cationic currents belonging to
voltage-gated channels. Also, we treated the cells with IGF-1 and PACAP, which
have previously been shown to protect MN-1 cells from the toxicity of mutant AR,
and we found an amelioration of the altered currents. Our results suggest that
the electrophysiological correlate of SBMA is a suitable reference point for the
identification of disease symptoms and for future therapeutic targets.
PMID- 28511916
TI - Pre-treatment with amitriptyline causes epigenetic up-regulation of
neuroprotection-associated genes and has anti-apoptotic effects in mouse neuronal
cells.
AB - Antidepressants, such as imipramine and fluoxetine, are known to alter gene
expression patterns by inducing changes in the epigenetic status of neuronal
cells. There is also some evidence for the anti-apoptotic effect of various
groups of antidepressants; however, this effect is complicated and cell-type
dependent. Antidepressants of the tricyclic group, in particular amitriptyline,
have been suggested to be beneficial in the treatment of neurodegenerative
disorders. We examined whether amitriptyline exerts an anti-apoptotic effect via
epigenetic mechanisms. Using DNA microarray, we analyzed global gene expression
in mouse primary cultured neocortical neurons after treatment with amitriptyline
and imipramine. The neuroprotection-associated genes, activating transcription
factor 3 (Atf3) and heme oxygenase 1 (Hmox1), were up-regulated at both mRNA and
protein levels by treatment with amitriptyline. Quantitative chromatin
immunoprecipitation assay revealed that amitriptyline increased enrichments of
trimethylation of histone H3 lysine 4 in the promoter regions of Atf3 and Hmox1
and acetylation of histone H3 lysine 9 in the promoter regions of Atf3, which
indicate an active epigenetic status. Amitriptyline pre-treatment attenuated 1
methyl-4-phenylpyridinium ion (MPP+)- or amyloid beta peptide 1-42 (Abeta1-42)
induced neuronal cell death and inhibited the activation of extracellular signal
regulated kinase 1 and 2 (ERK1/2). We found that Atf3 and Hmox1 were also up
regulated after Abeta1-42 treatment, and were further increased when pre-treated
with amitriptyline. Interestingly, the highest up-regulation of Atf3 and Hmox1,
at least at mRNA level, was observed after co-treatment with Abeta1-42 and
amitriptyline, together with the loss of the neuroprotective effect. These
findings suggest preconditioning and neuroprotective effects of amitriptyline;
however, further investigations are needed for clarifying the contribution of
epigenetic up-regulation of Atf3 and Hmox1 genes.
PMID- 28511917
TI - Evidence of the role of the vagal nerves as a monitor in the gastrointestinal
renal axis of natriuresis in human: Effects of vagotomy.
AB - This study aimed to investigate the mechanism of gastrointestinal regulation of
natriuresis. Sixteen subjects without (group I) and sixteen subjects with a
truncal vagotomy (group II), were given a daily diet of 18mmol of sodium for
5days (D1-D5). The sodium deficit for this period was calculated for each subject
and on the morning of day-6 (D6), their cumulative deficit (E) was given as 3%
NaCl. In both groups the subjects were divided to receive the hypertonic saline
either orally (Ior, IIor) or intravenously (Iiv, IIiv). During the period of low
sodium diet when compared to group II subjects of group I (1) had a greater
weight loss (p<0.005), (2) demonstrated a larger drop in pulse pressure
(p<0.005), (3) achieved a positive sodium equilibrium later (D5 vs D4) and (4)
developed a greater sodium deficit (p<0.005). During the two 12h periods of D6,
both Ior and Iiv exhibited greater natriuresis during the first 12h period
(p<0.0001) whereas both IIor and IIiv did so during the second 12h period
(p<0.0001). On D6 Ior excreted the greatest percentage of E (E%; 35.63%+/-3.12%,
p<0.0001) compared to Iiv (17.06%+/-1.78%), IIor (16.03%+/-3.54%) and IIiv
(15.39%+/-2.77%) whereas E% was not different between the other subgroups. These
results indicate that the differential natriuresis between oral and intravenous
sodium loading in previously sodium deprived subjects, is due to a mechanism in
which the vagal nerves play a significant role as part of neural reflex or via a
natriuretic hormone.
PMID- 28511919
TI - The debate: Treatment after the first seizure-The PRO.
AB - According to current diagnosis criteria, first seizures constitute beginning
epilepsy when they carry recurrence risks of >=60% over the next 10 years. This
is frequently the case and warrants AED treatment. Evidence argues against
deferring treatment when provoking factors such as sleep deprivation are
reported. There are several characteristics of first seizures which markedly
increase recurrence risk but not clearly beyond 60%. This includes status
epilepticus or seizure flurries at first manifestation or focal semiology
indicating focal epilepsy. In this situation, there are still various medical,
social and individual aspects supporting early initiation of AED. Modern AED
allow this safely and at low dosages.
PMID- 28511920
TI - The Girls-Only HPV Vaccination Program in British Columbia, Canada: A Qualitative
Study Exploring Expert Informants' Perspectives of Input From the Public.
PMID- 28511918
TI - Molecular imaging of serotonin degeneration in mild cognitive impairment.
AB - Neuropathological and neuroimaging studies have consistently demonstrated
degeneration of monoamine systems, especially the serotonin system, in normal
aging and Alzheimer's disease. The evidence for degeneration of the serotonin
system in mild cognitive impairment is limited. Thus, the goal of the present
study was to measure the serotonin transporter in vivo in mild cognitive
impairment and healthy controls. The serotonin transporter is a selective marker
of serotonin terminals and of the integrity of serotonin projections to cortical,
subcortical and limbic regions and is found in high concentrations in the
serotonergic cell bodies of origin of these projections (raphe nuclei). Twenty
eight participants with mild cognitive impairment (age 66.6+/-6.9, 16 males) and
28 healthy, cognitively normal, demographically matched controls (age 66.2+/-7.1,
15 males) underwent magnetic resonance imaging for measurement of grey matter
volumes and high-resolution positron emission tomography with well-established
radiotracers for the serotonin transporter and regional cerebral blood flow. Beta
amyloid imaging was performed to evaluate, in combination with the
neuropsychological testing, the likelihood of subsequent cognitive decline in the
participants with mild cognitive impairment. The following hypotheses were
tested: 1) the serotonin transporter would be lower in mild cognitive impairment
compared to controls in cortical and limbic regions, 2) in mild cognitive
impairment relative to controls, the serotonin transporter would be lower to a
greater extent and observed in a more widespread pattern than lower grey matter
volumes or lower regional cerebral blood flow and 3) lower cortical and limbic
serotonin transporters would be correlated with greater deficits in auditory
verbal and visual-spatial memory in mild cognitive impairment, not in controls.
Reduced serotonin transporter availability was observed in mild cognitive
impairment compared to controls in cortical and limbic areas typically affected
by Alzheimer's disease pathology, as well as in sensory and motor areas, striatum
and thalamus that are relatively spared in Alzheimer's disease. The reduction of
the serotonin transporter in mild cognitive impairment was greater than grey
matter atrophy or reductions in regional cerebral blood flow compared to
controls. Lower cortical serotonin transporters were associated with worse
performance on tests of auditory-verbal and visual-spatial memory in mild
cognitive impairment, not in controls. The serotonin system may represent an
important target for prevention and treatment of MCI, particularly the post
synaptic receptors (5-HT4 and 5-HT6), which may not be as severely affected as
presynaptic aspects of the serotonin system, as indicated by the observation of
lower serotonin transporters in MCI relative to healthy controls.
PMID- 28511922
TI - Simultaneous Transseptal Para-Ring Leak Closure and Transcatheter Mitral Valve
Implantation for the Treatment of Surgical Mitral Repair Failure.
AB - Repeat cardiac surgery in patients with a previous sternotomy is associated with
significant morbidity and mortality. While transcatheter aortic valve
implantation in high risk surgical patients is now well established, experience
with transcatheter mitral valve replacement is still at an early stage. Although
many successful reports of transcatheter mitral valve replacements now exist, the
predominant approach has been via a transapical approach. It is likely that, as
with the evolution of favoured access routes for transcatheter aortic therapies,
future directions for transcatheter mitral valves will focus on smaller delivery
systems favouring the transvenous transseptal approach where possible. We present
the first reported case of combined transseptal para-ring leak closure followed
by transcatheter mitral valve implantation using a 12/5mm Amplatzer III vascular
plug and a 29mm SAPIEN 3 valve.
PMID- 28511923
TI - IgG4-Aortopathy: An Underappreciated Cause of Non-Infectious Thoracic Aortitis.
AB - IgG4 related thoracic aortitis is a recent addition to the differential diagnosis
for inflammatory aortic disease - a condition which is often underappreciated
until complications arise such as aneurysmal formation or aortic dissection.
Currently, IgG4 aortitis remains a post-surgical diagnosis reliant on positive
immunohistochemistry findings. Management is guided by the extent of disease
involvement, which can be gauged by serum IgG4 levels and radiological findings.
Options include surgical resection, corticosteroid therapy and steroid-sparing
agents to prevent relapses.
PMID- 28511924
TI - Evaluation of the Effectiveness of a Phone Based Care Coordination Pilot on
Hospital Utilisation and Costs for Patients With Chest Pain.
AB - BACKGROUND: A small percentage of the population represents a disproportionate
number of attendances at emergency departments (ED). "Frequent presenters" to ED
with chest pain do not always fit into established pathways for acute myocardial
events. With accelerated "rule out" protocols, patients are often discharged from
the ED after short lengths of stay. This research will evaluate the effectiveness
of a phone based care-coordination pilot designed to meet the needs of patients
attending ED with cardiac and non-cardiac chest pain. METHODS: A longitudinal,
single-arm interventional study with retrospectively recruited control group.
Ninety-five patients were enrolled as the intervention group; 97 patients were
retrospectively identified as controls. These patients had re-presented with
chest pain within 6 months of a cardiac event, or attended hospital within 12
months two or more times with chest pain and/or complex needs. Intervention group
patients were holistically assessed then phone-coached to support self-management
of chest pain over 6 months. Following descriptive and univariate analysis,
multivariate analysis was conducted to adjust for noted differences between the
intervention and control groups. RESULTS: Thirty-day representation to ED was
significantly less for the intervention group (14.1%) compared to controls
(27.7%). After adjusting for baseline differences, intervention patients were
more than two-fold less likely to re-present compared to controls (OR=0.42,
95%CI: 0.19-0.96). After adjustment for baseline differences, the savings in
subsequent inpatient costs was $1588 per person, as a result of intervention,
patients were less likely to have inpatient readmissions (16.3%) compared to
controls (20.2%), although this was not statistically significant (p=0.588).
CONCLUSION: A phone based care-coordination pilot with targeted interventions has
the potential to reduce ED presentations and hospital readmissions among patients
representing with chest pain.
PMID- 28511926
TI - Fresh, frozen, or ambient food equivalents and their impact on food waste
generation in Dutch households.
AB - In Europe, it is estimated that more than 50% of total food waste - of which most
is avoidable - is generated at household level. Little attention has been paid to
the impact on food waste generation of consuming food products that differ in
their method of food preservation. This exploratory study surveyed product
specific possible impacts of different methods of food preservation on food waste
generation in Dutch households. To this end, a food waste index was calculated to
enable relative comparisons of the amounts of food waste from the same type of
foods with different preservation methods on an annual basis. The results show
that, for the majority of frozen food equivalents, smaller amounts were wasted
compared to their fresh or ambient equivalents. The waste index (WI) proposed in
the current paper confirms the hypothesis that it may be possible to reduce the
amount of food waste at household level by encouraging Dutch consumers to use
(certain) foods more frequently in a frozen form (instead of fresh or ambient).
However, before this approach can be scaled to population level, a more detailed
understanding of the underlying behavioural causes with regard to food
provisioning and handling and possible interactions is required.
PMID- 28511921
TI - Myeloperoxidase: A new player in autoimmunity.
AB - Myeloperoxidase (MPO) is the most toxic enzyme found in the azurophilic granules
of neutrophils. MPO utilizes H2O2 to generate hypochlorous acid (HClO) and other
reactive moieties, which kill pathogens during infections. In contrast, in the
setting of sterile inflammation, MPO and MPO-derived oxidants are thought to be
pathogenic, promoting inflammation and causing tissue damage. In contrast,
evidence also exists that MPO can limit the extent of immune responses. Elevated
MPO levels and activity are observed in a number of autoimmune diseases including
in the central nervous system (CNS) of multiple sclerosis (MS) and the joints of
rheumatoid arthritis (RA) patients. A pathogenic role for MPO in driving
autoimmune inflammation was demonstrated using mouse models. Mechanisms whereby
MPO is thought to contribute to disease pathogenesis include tuning of adaptive
immune responses and/or the induction of vascular permeability.
PMID- 28511925
TI - Total Correction of Tetralogy of Fallot at Early Age: A Study of 183 Cases.
AB - BACKGROUND: Opinions regarding the optimal time for the repair of tetralogy of
Fallot vary. A debate also exists about the timing of repair for the asymptomatic
infant. METHODS: This study included 183 patients with tetralogy of Fallot. All
patients were subjected to clinical examination with measurement of oxygen
saturation, 12-lead ECG, plain chest x-ray, and complete laboratory
investigation. Echocardiography and cardiac catheterisation were indicated if
there was an inability to reach diagnosis by echocardiography, suspicion of
coronary anomaly, evaluation of distal pulmonary arteries or suspicion of major
aorto-pulmonary collaterals. Complete repair was done in all patients. Patients
were divided into two groups for comparison. Group 1 (147 patients, 1-year-old or
less), and Group 2 (36 patients older than 1 year). RESULTS: Three patients died
in Group1 (2.04%) while there was no early mortality in Group 2 patients. Six
patients in Group 1 (4.08%) were reoperated for significant residual or recurrent
right ventricular outflow stenosis, three patients (2.04%) were reoperated for
residual significant shunt, and three patients (2.04%) were reoperated for
residual significant stenosis and residual significant shunt. That is in addition
to three patients (2.04%) who had significant tricuspid regurgitation, three more
patients (2.04%) who needed a permanent pacemaker implantation, and nine patients
(6.1%) who had significant postoperative pulmonary valve regurgitation. On the
other hand, for Group 2 patients, there were only three patients who were
reoperated for postoperative restenosis and significant shunt, three patients who
were reoperated for permanent pacemaker implantation, and another two patients
who had insignificant restenosis to be followed up. CONCLUSIONS: Early complete
tetralogy of Fallot repair can be accomplished with a low mortality.
PMID- 28511927
TI - Coordinated regulation of IFITM1, 2 and 3 genes by an IFN-responsive enhancer
through long-range chromatin interactions.
AB - Interferon-induced transmembrane protein (IFITM) 1, 2 and 3 genes encode a family
of interferon (IFN)-induced transmembrane proteins that block entry of a broad
spectrum of pathogens. However, the transcriptional regulation of these genes,
especially whether there exist any enhancers and their roles during the IFN
induction process remain elusive. Here, through public data mining, episomal
luciferase reporter assay and in vivo CRISPR-Cas9 genome editing, we identified
an IFN-responsive enhancer located 35kb upstream of IFITM3 gene promoter
upregulating the IFN-induced expression of IFITM1, 2 and 3 genes. Chromatin
immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA) and
luciferase reporter assay demonstrated that signal transducers and activators of
transcription (STAT) 1 bound to the enhancer with the treatment of IFN and was
indispensable for the enhancer activity. Furthermore, using chromosome
conformation capture technique, we revealed that the IFITM1, 2 and 3 genes
physically clustered together and constitutively looped to the distal enhancer
through long-range interactions in both HEK293 and A549 cells, providing
structural basis for coordinated regulation of IFITM1, 2 and 3 by the enhancer.
Finally, we showed that in vivo truncation of the enhancer impaired IFN-induced
resistance to influenza A virus (IAV) infection. These findings expand our
understanding of the mechanisms underlying the transcriptional regulation of
IFITM1, 2 and 3 expression and its ability to mediate IFN signaling.
PMID- 28511929
TI - Clinical Characteristics of Pertussis-Associated Cough in Adults and Children: A
Diagnostic Systematic Review and Meta-Analysis.
AB - BACKGROUND: Pertussis (whooping cough) is a highly infective cause of cough that
causes significant morbidity and mortality. Existing case definitions include
paroxysmal cough, whooping, and posttussive vomiting, but diagnosis can be
difficult. We determined the diagnostic accuracy of clinical characteristics of
pertussis-associated cough. METHODS: We systematically searched CINAHL, Embase,
Medline, and SCI-EXPANDED/CPCI-S up to June 2016. Eligible studies compared
clinical characteristics in those positive and negative for Bordetella pertussis
infection, confirmed by laboratory investigations. Two authors independently
completed screening, data extraction, and quality and bias assessments. For each
characteristic, RevMan was used to produce descriptive forest plots. The
bivariate meta-analysis method was used to generate pooled estimates of
sensitivity and specificity. RESULTS: Of 1,969 identified papers, 53 were
included. Forty-one clinical characteristics were assessed for diagnostic
accuracy. In adult patients, paroxysmal cough and absence of fever have a high
sensitivity (93.2% [CI, 83.2-97.4] and 81.8% [CI, 72.2-88.7], respectively) and
low specificity (20.6% [CI, 14.7-28.1] and 18.8% [CI, 8.1-37.9]), whereas
posttussive vomiting and whooping have low sensitivity (32.5% [CI, 24.5-41.6] and
29.8% [CI, 8.0-45.2]) and high specificity (77.7% [CI, 73.1-81.7] and 79.5% [CI,
69.4-86.9]). Posttussive vomiting in children is moderately sensitive (60.0% [CI,
40.3-77.0]) and specific (66.0% [CI, 52.5-77.3]). CONCLUSIONS: In adult patients,
the presence of whooping or posttussive vomiting should rule in a possible
diagnosis of pertussis, whereas the lack of a paroxysmal cough or the presence of
fever should rule it out. In children, posttussive vomiting is much less helpful
as a clinical diagnostic test.
PMID- 28511930
TI - Bed morphological features associated with an optimal slurry concentration for
reproducible preparation of efficient capillary ultrahigh pressure liquid
chromatography columns.
AB - Column wall effects and the formation of larger voids in the bed during column
packing are factors limiting the achievement of highly efficient columns.
Systematic variation of packing conditions, combined with three-dimensional bed
reconstruction and detailed morphological analysis of column beds, provide
valuable insights into the packing process. Here, we study a set of sixteen 75MUm
i.d. fused-silica capillary columns packed with 1.9MUm, C18-modified, bridged
ethyl hybrid silica particles slurried in acetone to concentrations ranging from
5 to 200mg/mL. Bed reconstructions for three of these columns (representing low,
optimal, and high slurry concentrations), based on confocal laser scanning
microscopy, reveal morphological features associated with the implemented slurry
concentration, that lead to differences in column efficiency. At a low slurry
concentration, the bed microstructure includes systematic radial heterogeneities
such as particle size-segregation and local deviations from bulk packing density
near the wall. These effects are suppressed (or at least reduced) with higher
slurry concentrations. Concomitantly, larger voids (relative to the mean particle
diameter) begin to form in the packing and increase in size and number with the
slurry concentration. The most efficient columns are packed at slurry
concentrations that balance these counteracting effects. Videos are taken at low
and high slurry concentration to elucidate the bed formation process. At low
slurry concentrations, particles arrive and settle individually, allowing for
rearrangements. At high slurry concentrations, they arrive and pack as large
patches (reflecting particle aggregation in the slurry). These processes are
discussed with respect to column packing, chromatographic performance, and bed
microstructure to help reinforce general trends previously described. Conclusions
based on this comprehensive analysis guide us towards further improvement of the
packing process.
PMID- 28511931
TI - Water-compatible micron-sized monodisperse molecularly imprinted beads for
selective extraction of five iridoid glycosides from Cornus officinalis fructus.
AB - An efficient, accurate and sensitive method for the determination of five iridoid
glycosides (IGs) in Cornus officinalis fructus using molecularly imprinted solid
phase extraction (MISPE) coupled with high performance liquid chromatography
(HPLC) has been developed. Water-compatible molecularly imprinted beads (MIBs)
were synthesized by precipitation polymerization, using alkenyl glycosides
glucose as the hydrophilic functional monomer. Scanning electron microscopy
showed that the MIBs had a narrow particle size distribution, with diameters in
the range 7.5-9.3MUm. The special molecular recognition by the MIBs of IGs in
aqueous media was verified by static adsorption, kinetic adsorption, and
selectivity experiments. The newly prepared MIBs were used as sorbents in solid
phase extraction (SPE) for the selective recognition of five IGs (loganin,
morroniside, loganic acid, 7-O-ethyl-morroniside and 7-O-methyl morroniside) in
Cornus officinalis fructus. When optimized, the MISPE-HPLC method had good
linearity (0.02-100mgg-1), with correlation coefficient (R)>=0.994. Recoveries at
three spiked levels were in the range 80.0%-94.0%. Because of its excellent
specificity and hydrophilicity, SPE based on monodisperse MIBs provides a
promising pretreatment strategy for the analysis of active components in natural
products, especially for the quality control of traditional Chinese medicines.
PMID- 28511932
TI - Determination of piperidinium ionic liquid cations in environmental water samples
by solid phase extraction and hydrophilic interaction liquid chromatography.
AB - This paper presents a novel analytical method for the determination of
piperidinium ionic liquid cations in environmental water by hydrophilic
interaction liquid chromatography and solid-phase extraction technology. The left
standing, centrifuged and filtered river water samples were first purified and
concentrated through the C18 solid phase extraction column, and eluted with
0.02mol/L hydrochloric acid prepared in methanol and deionized water (80/20,
v/v). Then the eluents were analyzed by a hydrophilic column combined with
0.8mmol/L 1-propyl-3-methyl imidazolium tetrafluoroborate aqueous
solution/acetonitrile (40/60, v/v) as the mobile phase and indirect ultraviolet
detection. The detection limits of piperidinium cations were less than 0.4mg/L.
The relative standard deviations were less than 0.6%. The method has been
successfully applied to the determination of piperidinium cations in Songhua
River water samples. Recoveries were 80.0%-98.3%. This research may provide a
reference for studying the environmental effect of ionic liquids.
PMID- 28511933
TI - An initial demonstration of hierarchically porous niobium alkylphosphonates
coordination polymers as potent radioanalytical separation materials.
AB - Combining the merits of soft-templating and perchlorate oxidation methods, the
first-case investigation of niobium alkylphosphonates has uncovered their unique
morphology, backbone composition, thermal behavior and huge potentiality as
radioanalytical separation materials. These hierarchically porous solids are
random aggregates of densely stacked nanolayers perforated with worm-like holes
or vesicular voids, manifesting the massif-, tower-like "polymer brush" elevated
up to ~150nm driven by the minimal surface free energy principle. These
coordination polymers consist of distorted niobium (V) ions strongly linked with
tetrahedral alkylphosphonate building units, exposing uncoordinated phosphonate
moieties and defective metal sites. Despite the amorphous features, they
demonstrate multimodal porosity covering continuous micropores, segregated
mesopores and fractional macropores, beneficial for the sequestration by active
Lewis acid-base center. Evidenced by the maximum distribution coefficients of
thorium, lanthanides reaching 9.0*104, 9.5*104mLg-1 and large separation factor
at pH<=1 20-element cocktail, this category of niobium alkylphosphonates are
capable of harvesting thorium, lanthanides directly from the radionuclide
surrogate, comparable to or even surpass the performance of the metal (IV)
arylphosphonates counterparts. They also display appreciable SFEu/Sm ~20 in 1molL
1 HNO3, shedding light on dual approaches to achieve the isolation of americium
from curium. A combinatorial radioanalytical separation protocol has been
proposed to enrich thorium and europium, revealing facile utilization of these
highly stable, phosphonated hybrids in sustainable development of radioanalytical
separation.
PMID- 28511928
TI - Rational design of nanoparticles towards targeting antigen-presenting cells and
improved T cell priming.
AB - Vaccination is a promising strategy to trigger and boost immune responses against
cancer or infectious disease. We have designed, synthesized and characterized
aliphatic-polyester (poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) to
investigate how the nature of protein association (adsorbed versus entrapped) and
polymer/surfactant concentrations impact on the generation and modulation of
antigen-specific immune responses. The ability of the NP formulations to target
dendritic cells (DC), be internalized and activate the T cells was characterized
and optimized in vitro and in vivo using markers of DC activation and co
stimulatory molecules. Ovalbumin (OVA) was used as a model antigen in combination
with the engraftment of CD4+ and CD8+ T cells, carrying a transgenic OVA
responding T cell receptor (TCR), to trace and characterize the activation of
antigen-specific CD4+ and CD8+ lymph node T cells upon NP vaccination.
Accordingly, the phenotype and frequency of immune cell stimulation induced by
the NP loaded with OVA, isolated or in combination with synthetic unmethylated
cytosine-phosphate-guanine (CpG) oligodeoxynucleotide (ODN) motifs, were
characterized. DC-NP interactions increased with incubation time, presenting
internalization values between 50 and 60% and 30-40%, in vitro and in vivo,
respectively. Interestingly, animal immunization with antigen-adsorbed NP up
regulated major histocompatibility complex (MHC) class II (MHCII), while NP
entrapping the antigen up-regulated MHCI, suggesting a more efficient cross
presentation. On the other hand, rather surprisingly, the surfactant used in the
NP formulation had a major impact on the activation of antigen presenting cells
(APC). In fact, DC collected from lymph nodes of animals immunized with NP
prepared using poly(vinil alcohol) (PVA), as a surfactant, expressed
significantly higher levels of CD86, MHCI and MHCII. In addition, those NP
prepared with PVA and co-entrapping OVA and the toll-like receptor (TLR) ligand
CpG, induced the most profound antigen-specific T cell response, by both CD4+ and
CD8+ T cells, in vivo. Overall, our data reveal the impact of NP composition and
surface properties on the type and extension of induced immune responses. Deeper
understanding on the NP-immune cell crosstalk can guide the rational development
of nano-immunotherapeutic systems with improved and specific therapeutic efficacy
and avoiding off-target effects.
PMID- 28511934
TI - Repeated manganese administration produced abnormal expression of circadian clock
genes in the hypothalamus and liver of rats.
AB - Manganese (Mn) neurotoxicity displays non-motor dysfunction and motor impairment
like Parkinson's disease (PD), and is called as Manganism. Circadian disruption
is a non-motor symptom found in PD and Manganism. Clock genes are essential to
drive and maintain circadian rhythm, but little is known about Mn exposure on
circadian clock genes expression. Both the brain and liver are targets of Mn, we
hypothesize that repeated Mn administration could affect clock gene expression in
the hypothalamus and livers. Male Sprague-Dawley rats were intraperitoneally
injected Mn2+ 1mg and 5mg/kg as MnCl2.4H2O, every other day for 30 days. Mn
neurotoxicity was evaluated by behavioral changes and loss of dopaminergic
neurons via immunohistochemistry. The expression of circadian clock genes was
determined via RT-qPCR. Repeated Mn administration dose-dependently retarded the
body weight gain, impaired the rotarod activity, decreased the number of
dopaminergic neurons in the substantia nigra, and activated microglia in the
brain. Expressions of circadian core genes brain and muscle Arnt-like protein-1
(Bmal1), locomotor output cycles kaput (Clock) and neuronal PAS domain protein2
(Npas2), and clock feedback gene cryptochrome1 (Cry1), period genes (Per1 and
Per2) in the hypothalamus and liver were decreased after exposure to Mn in a dose
dependent manner, while expressions of clock-targeted genes nuclear receptor Rev
Erbalpha (Nr1d1) and D-box-binding protein (Dbp) were increased. Peripheral clock
in the liver appears to be more susceptible to Mn-induced abnormal clock gene
expression. In summary, repeated Mn administration produced dysregulation of
circadian clock gene expressions in both the brain and liver.
PMID- 28511935
TI - Bile acids and male fertility: From mouse to human?
AB - Next to their involvement in digestion, bile acids have been defined as signaling
molecules. They have been demonstrated to control many physiological functions
among which lipid homeostasis, glucose and energy metabolisms. Bile acids are
ligands of several receptors and multiple studies using transgenic mouse models
defined the major roles of their respective nuclear and membrane receptors namely
the Farnesoid-X-Receptor (FXRalpha) and the G-protein-coupled bile acid receptor
1(GPBAR1; TGR5). Here we review the reports highlighting the impacts of bile
acids on testicular physiology and on male reproductive functions. The studies on
mouse models open perspectives to better understand the deleterious effects of
bile acids on testicular pathophysiologies and fertility disorders. Additional
studies are needed to corroborate these correlations in humans.
PMID- 28511936
TI - Biotechnologies for Marine Oil Spill Cleanup: Indissoluble Ties with
Microorganisms.
AB - The ubiquitous exploitation of petroleum hydrocarbons (HCs) has been accompanied
by accidental spills and chronic pollution in marine ecosystems, including the
deep ocean. Physicochemical technologies are available for oil spill cleanup, but
HCs must ultimately be mineralized by microorganisms. How environmental factors
drive the assembly and activity of HC-degrading microbial communities remains
unknown, limiting our capacity to integrate microorganism-based cleanup
strategies with current physicochemical remediation technologies. In this review,
we summarize recent findings about microbial physiology, metabolism and ecology
and describe how microbes can be exploited to create improved biotechnological
solutions to clean up marine surface and deep waters, sediments and beaches.
PMID- 28511937
TI - Hot Start to European Pluripotent Stem Cell Banking.
AB - Achieving consistency in standards of access to and quality of human induced
pluripotent stem cells has lagged behind their use. In Europe, a network of
academic and industrial partners has been established to overcome this challenge.
The experience reveals the devil in the detail of worthy ambitions informing
future efforts.
PMID- 28511938
TI - Floating marine litter as a raft for drifting voyages for Planes minutus
(Crustacea: Decapoda: Grapsidae) and Liocarcinus navigator (Crustacea: Decapoda:
Polybiidae).
AB - The Columbus crab Planes minutus and Arch-fronted swimming crab Liocarcinus
navigator, within their distribution ranges in the Mediterranean, were found
rafted on plastic macro-litter floating on the open south Adriatic. While P.
minutus was recorded from inanimate flotsam outside of the Mediterranean, L.
navigator is herein reported for the first time on floating marine litter. The
role of floating litter as habitat or as a dispersal agent for marine
invertebrates has received quite attention however, records of decapod crabs
drifting on litter has been relatively sparse. Our results suggests that vast
quantities of floating debris, comprised primarily of non-biodegradable plastic
polymers, probably will augment natural floating substrates in the marine
environment, potentially facilitating the spread of invasive species. The
dispersion of rafting crabs through floating debris should be investigated given
the high potential ecological risk of invasion by exotic species due to the
increase in waste production (ecological risk assessment).
PMID- 28511939
TI - Droplet and bubble formation of combined oil and gas releases in subsea blowouts.
AB - Underwater blowouts from gas and oil operations often involve the simultaneous
release of oil and gas. Presence of gas bubbles in jets/plumes could greatly
influence oil droplet formation. With the aim of understanding and quantifying
the droplet formation from Deepwater Horizon blowout (DWH) we developed a new
formulation for gas-oil interaction with jets/plumes. We used the jet-droplet
formation model VDROP-J with the new module and the updated model was validated
against laboratory and field experimental data. Application to DWH revealed that,
in the absence of dispersant, gas input resulted in a reduction of d50 by up to
1.5mm, and maximum impact occurred at intermediate gas fractions (30-50%). In the
presence of dispersant, reduction in d50 due to bubbles was small because of the
promoted small sizes of both bubbles and droplets by surfactants. The new
development could largely enhance the prediction and response to oil and gas
blowouts.
PMID- 28511940
TI - Comparative efficacy of benthic biotic indices in assessing the Ecological
Quality Status (EcoQS) of the stressed Ulhas estuary, India.
AB - Ecostatus of Ulhas estuary, one of the most polluted estuaries along the
industrialized and urbanized northwest coast of India, was evaluated by six
widely accepted benthic indices viz. H'(log2), AMBI, M-AMBI, BENTIX, BOPA and
BO2A to test their efficiency in a tropical setting. The mesohaline zone, which
presented eutrophic conditions, was classified as 'bad' by all indices due to the
azoic status. Despite significant correlations obtained between indices, there
were discrepancies in the accurate level of EcoQS assigned to each station. AMBI
was observed to be most efficient in indicating a clear spatial variability from
a 'poor' to 'bad' ecological quality status in the middle and upstream zones to
an improved status in the downstream region. Limitations of all indices are
discussed in light of their suitability for assessing the estuarine environmental
condition. The present results could provide a fillip to environmental
improvement initiatives currently being undertaken in the estuary.
PMID- 28511941
TI - Effects of ocean acidification on the physiological performance and carbon
production of the Antarctic sea ice diatom Nitzschia sp. ICE-H.
AB - Ocean acidification (OA) resulting from increasing atmospheric CO2 strongly
influences marine ecosystems, particularly in the polar ocean due to greater CO2
solubility. Here, we grew the Antarctic sea ice diatom Nitzschia sp. ICE-H in a
semicontinuous culture under low (~400ppm) and high (1000ppm) CO2 levels.
Elevated CO2 resulted in a stimulated physiological response including increased
growth rates, chlorophyll a contents, and nitrogen and phosphorus uptake rates.
Furthermore, high CO2 enhanced cellular particulate organic carbon production
rates, indicating a greater shift from inorganic to organic carbon. However, the
cultures grown in high CO2 conditions exhibited a decrease in both extracellular
and intracellular carbonic anhydrase activity, suggesting that the carbon
concentrating mechanisms of Nitzschia sp. ICE-H may be suppressed by elevated
CO2. Our results revealed that OA would be beneficial to the survival of this sea
ice diatom strain, with broad implications for global carbon cycles in the future
ocean.
PMID- 28511943
TI - Relationship between soluble CD25 and gene expression in healthy individuals and
patients with multiple sclerosis.
AB - Genome wide association studies and fine mapping has established a firm link
between the IL2RA gene, encoding the interleukin-2 receptor alpha-chain CD25, and
susceptibility to multiple sclerosis (MS). We hypothesized that gene expression
in peripheral blood mononuclear cells (PBMCs) from healthy controls (HCs) and MS
patients are associated with IL2RA SNP rs2104286 and that gene expression levels
correlate with soluble CD25 (sCD25) concentrations - that are affected by
rs2104286. We used the Affymetrix Human Gene ST 1.0 microarray to analyze gene
expression levels in PBMCs from 18 HCs and 51MS patients. Plasma concentrations
of sCD25 were measured by ELISA in all individuals. In HCs 266 genes correlated
with sCD25 with Spearman's rho>=0.707; 70 of these genes had a false discovery
rate (FDR) value of q<0.05. These genes were highest expressed in cells belonging
to the innate immune system. Gene-networks were focused around NFKB1, TNF, BCL6
and STAT1. Eighteen genes correlated with sCD25 with rho>=0.707 in relapsing
remitting MS versus 33 in secondary progressive and 34 in primary progressive MS.
None had a FDR<0.05. Thirty-eight and 23 genes were differentially expressed
between rs2104286 genotype-groups in MS patients and HCs respectively, however
they were not significant after FDR correction. Our study indicates that
rs2104286 influences gene expression in PBMCs in HCs as shown by the high
correlations with the rs2104286-affected sCD25 protein. Correlations were
strongest in HCs suggesting that immunological alterations may obscure the role
of the IL2RA SNP rs2104286 in established MS.
PMID- 28511942
TI - Effect of resistant and digestible rice starches on human cytokine and lactate
metabolic networks in serum.
AB - Resistant starch generated after treating ordinary starch is of great
significance to human health in the countries with overnutrition. However, its
functional evaluation in the human body has been rarely reported. By determining
the lactate metabolic flux, 12 serum enzymes expression level and 38 serum
cytokines in healthy volunteers, the variation in cytokine network and lactate
metabolic network in serum were investigated to compare the mechanism of the
physiological effects between the two starches. The results indicated that
compared with digestible starch, resistant starch had anti-inflammatory effects,
increased anabolism, and decreased catabolism. Further, the intercellular
communication networks including cytokine and lactate metabolic networks were
mapped out. The relationship suggested that resistant starch might affect and
control the secretion of cytokines to regulate lactate metabolic network in the
body, promoting the development of immunometabolism.
PMID- 28511944
TI - Serum periostin in patients hospitalized for COPD exacerbations.
AB - Serum periostin has been proposed as a surrogate biomarker of Th2 inflammatory
response in patients with asthma, but its predictive role in hospitalized
patients with COPD has not been evaluated. The aim of the present observational
prospective cohort study was to evaluate the possible role of serum periostin as
predictor of outcome in COPD patients hospitalized for AECOPD. Serum periostin
was measured on admission and at discharge in patients admitted to the hospital
for a COPD exacerbation. Patients were followed-up for 1year for future
exacerbations, hospitalizations and mortality. 155 consecutive patients admitted
to the hospital for AECOPD were included to the study. Periostin levels on
admission were elevated compared to discharge [34.7 (25.2-52.2) vs. 25.9 (17.4
41.0) ng/mL, p=0.003], but serum periostin levels did not differ between patients
with or without prolonged hospitalization, or those who required non-invasive
ventilation, intubation, or died during hospitalization. Frequent exacerbators
had higher serum periostin levels at the time of discharge compared to non
frequent exacerbators [37.9 (26.6, 64.5) vs. 23.9 (16.2, 37.9), p<0.001].
Periostin levels above the median value (25ng/mL) were not related to the time of
next exacerbation, time of next COPD hospitalization, (p=0.858) or time to death.
The role of serum periostin levels as a predictive biomarker of future risk in
hospitalized patients with COPD is of limited value.
PMID- 28511945
TI - Low Rates of Aseptic Tibial Loosening in Obese Patients With Use of High
Viscosity Cement and Standard Tibial Tray: 2-Year Minimum Follow-Up.
AB - BACKGROUND: Total knee arthroplasty is overall a very successful surgery, but
complications do occur. These complications include aseptic loosening of the
tibial component, and obese patients are among the highest risk group. High
viscosity cement (HVC) has been implicated as a possible cause for aseptic
loosening of the tibial component. The purpose of this study was to evaluate the
incidence of aseptic loosening of the tibial component in obese patients with the
use of HVC and standard tibial tray. METHODS: We identified 1366 obese patients
(1851 knees) with a body mass index >35 kg/m2 and 2-year minimum follow-up who
underwent primary total knee arthroplasty using HVC and a symmetrical, grit
blasted, cobalt-chrome tibial component with 40-mm stem. Preoperative and
postoperative range of motion, Knee Society (KS) scores, complications, and
reoperations were evaluated. Specifically, we assessed the rate of tibial aseptic
loosening. RESULTS: At a mean 5.4 years follow-up, only 1 in 1851 knees had
aseptic loosening of the tibial component for an incidence of 0.054%. There was a
mean increase of 3.3 degrees of knee range of motion. KS pain level decreased by
38.6 points (50 point scale). KS clinical scores improved by 52.2, Knee Society
functional scores improved by 19.5, University of California, Los Angeles,
activity score improved by 0.9, and Oxford Knee Score by 15.7. All these
improvements were statistically significant with P < .001. CONCLUSION: Standard
tibial components and HVC can be used in most patients, including the high-risk
obese group, with low rates of tibial aseptic loosening.
PMID- 28511946
TI - National Incidence of Patient Safety Indicators in the Total Hip Arthroplasty
Population.
AB - BACKGROUND: The Centers for Medicare & Medicaid Services use the incidence of
patient safety indicators (PSIs) to determine health care value and hospital
reimbursement. The national incidence of PSI has not been quantified in the total
hip arthroplasty (THA) population, and it is unknown if patient insurance status
is associated with PSI incidence after THA. METHODS: All patients in the
Nationwide Inpatient Sample (NIS) who underwent THA in 2013 were identified using
the International Classification of Diseases, Ninth Revision, Clinical
Modification codes. The incidence of PSI was determined using the International
Classification of Diseases, Ninth Revision, diagnosis code algorithms published
by the Centers for Medicare & Medicaid Services and the Agency for Healthcare
Research and Quality. The association of insurance status and the incidence of
PSI during the inpatient episode was determined by comparing privately insured
and Medicare patients with Medicaid/self-pay patients using a logistic regression
model that controlled for patient demographics, patient comorbidities, and
hospital characteristics. RESULTS: In 2013, the NIS included 68,644
hospitalizations with primary THA performed during the inpatient episode. During
this period, 429 surgically relevant PSI were recorded in the NIS. The estimated
national incidence rate of PSI after primary THA was 0.63%. In our secondary
analysis, the privately insured cohort had significantly lower odds of
experiencing one or more PSIs relative to the Medicaid/self-pay cohort (odds
ratio, 0.47; 95% confidence interval, 0.29-0.76). CONCLUSION: The national
incidence of PSI among THA patients is relatively low. However, primary insurance
status is associated with the incidence of one or more PSIs after THA. As value
based payment becomes more widely adopted in the United States, quality
benchmarks and penalty thresholds need to account for these differences in risk
adjustment models to promote and maintain access to care in the underinsured
population.
PMID- 28511947
TI - Intraoperative Femur Fracture Risk During Primary Direct Anterior Approach
Cementless Total Hip Arthroplasty With and Without a Fracture Table.
AB - BACKGROUND: There is no study to date comparing intraoperative femur fractures
(IFFs) in the direct anterior approach (DAA) with and without a fracture table.
We hypothesize that there is no significant difference in the IFF with and
without a fracture table when performed by experienced DAA hip surgeons. METHODS:
This study is a 1-year retrospective review of patients who underwent DAA total
hip arthroplasty by 2 surgeons: one surgeon uses a flat table and manually
elevates the femur with a large bone hook, while the other surgeon uses a
fracture table and a mechanical femoral elevator. Exclusion criteria included
cemented femoral implants, femoral neck fractures, and lack of 6-month follow-up.
RESULTS: We identified 487 patients for analysis (220 male and 267 female,
average age 66.55 years). There were 12 total IFFs (2.46%): 8 female and 4 male
patients. The average age of IFF patients was 70.67 years and in nonfracture
patients was 66.00 years. There was no difference in gender (P = .2981) or age (P
= .2099) between IFF and nonfracture patients. In the fracture table group, there
were 6 IFFs (2.22%) in 271 patients; in the nonfracture table group, there were 6
IFFs (2.76%) in 216 patients. There was no statistical difference in IFF between
the 2 groups (P = .6973). We observed just 2 patients (0.4%) in this series where
the IFFs changed management requiring a revision femoral stem. CONCLUSION: There
was no statistical difference in IFF with or without the use of fracture table.
Both DAA surgical technique variations are felt to be equivalent regarding the
risk for IFF during DAA cementless total hip arthroplasty.
PMID- 28511948
TI - Computer Navigation Helps Reduce the Incidence of Noise After Ceramic-on-Ceramic
Total Hip Arthroplasty.
AB - BACKGROUND: Noise after ceramic-on-ceramic (CoC) total hip arthroplasty (THA) is
a well-recognized problem. Computer navigation has been shown to achieve desired
implant orientation. Our aim was (1) to compare the incidence of noise between
navigated and conventional CoC THAs and (2) to determine the factors associated
with noise. METHODS: All patients undergoing CoC THA between March 2009 and
August 2012 were considered for this study. Information regarding hip noise was
obtained via telephone or postal interview. A comparable cohort of patients in
navigated and conventional groups was used to evaluate the incidence of noise.
RESULTS: A total of 375 CoC THAs using the same implant (202 navigated and 173
conventional) were evaluated. Patients <65 years of age had significantly greater
incidence of noise (22.4% vs 6.1%; P < .001). To ensure similarity, a subgroup of
cohort <65 years and a 32-mm head size was used to compare the incidence of noise
between the navigated (68 THAs) and conventional (118 THAs) groups. Overall
incidence of noise was significantly greater in the conventional group (28%) as
compared with the navigated group (10%; P = .005). The relative risk of noise for
the conventional vs the navigated group was 2.7 (P = .01), and for squeaking was
1.9 (P = .2). Squeaking THAs had significantly lower cup anteversion (13.4
degrees +/- 5.2 degrees ) as compared with the silent THAs (17.6 degrees +/-
6.9 degrees ; P = .01). CONCLUSION: Navigated CoC THAs were 2.7* less likely to
have noise as compared with the conventional ones. Squeaking THAs had
significantly lower cup anteversion as compared with the silent ones. Patients of
age <65 years had significantly greater incidence of noise after CoC THA.
PMID- 28511950
TI - Benign Mullerian Inclusions in Lymphadenectomies for Renal Cell Carcinoma: A
Radiologic and Pathologic Mimic of Metastases.
PMID- 28511949
TI - Serum Metal Levels for Diagnosis of Adverse Local Tissue Reactions Secondary to
Corrosion in Metal-on-Polyethylene Total Hip Arthroplasty.
AB - BACKGROUND: Recently, corrosion at the head-neck junction in metal-on
polyethylene bearing surface total hip arthroplasty (THA) has been recognized as
a cause of adverse local tissue reactions (ALTRs). Serum metal levels have been
advocated as a tool for the diagnosis of ALTR; however, no prior studies have
specifically examined their utility. The purpose of this study was to determine
the optimal cutoff values for serum cobalt and chromium levels in diagnosing ALTR
after metal-on-polyethylene bearing surface THA. METHODS: We reviewed 447
consecutive patients with serum metal levels tested at our institution and
identified 64 patients with a metal-on-polyethylene bearing who had axial imaging
or underwent reoperation to confirm the presence or absence of ALTR. Receiver
operating characteristic curves were produced to identify cutoff thresholds to
optimize sensitivity, and diagnostic test performance was characterized. RESULTS:
Forty-four of the 64 patients (69%) were positive for an ALTR. The best test for
the diagnosis of ALTR was the serum cobalt level (area under the curve [AUC] =
99%). A threshold cutoff of >=1.0 ng/mL had a sensitivity of 100%, specificity of
90%, positive predictive value (PPV) of 96%, and negative predictive value (NPV)
of 100%. Serum chromium levels were also diagnostic (AUC = 87%). A threshold
cutoff of >=0.15 ng/mL had a sensitivity of 100%, specificity of 50%, PPV of 81%,
and NPV of 100%. Finally, serum cobalt-to-chromium ratio was also helpful for
diagnosis (AUC = 90%). A threshold cutoff value of 1.4 for the cobalt-to-chromium
ratio offered a sensitivity of 93%, specificity of 70%, PPV of 87%, and NPV of
82%. CONCLUSION: Measurement of serum cobalt level with a threshold value of 1.0
ng/mL in our experience is the best test for identifying the presence of ALTR in
patients with a metal-on-polyethylene THA. Measurement of chromium level and the
ratio of cobalt-to-chromium levels are also of value.
PMID- 28511952
TI - Lithium ameliorates lipopolysaccharide-induced neurotoxicity in the cortex and
hippocampus of the adult rat brain.
AB - Lithium an effective mood stabilizer, primary used in the treatment of bipolar
disorders, has been reported as a protective agent in various neurological
disorders. In this study, we examined the neuroprotective role of lithium
chloride (LiCl) against lipopolysaccharide (LPS) in the cortex and hippocampus of
the adult rat brain. We determined that LiCl -attenuated LPS-induced activated
toll-like receptor 4 (TLR4) signalling and significantly reduced the nuclear
factor-kB (NF-KB) translation factor and various other inflammatory mediators
such as interleukin-1 beta (IL-1beta) and tumour necrosis factor alpha (TNF
alpha). We also analyzed that LiCl significantly abrogated activated gliosis via
attenuation of specific markers for activated microglia, ionized calcium-binding
adaptor molecule (Iba-1) and astrocytes, glial fibrillary acidic protein (GFAP)
in both the cortex and hippocampus of the adult rat brain. Furthermore, we also
observed that LiCl treatment significantly ameliorated the increase expression
level of apoptotic neurodegeneration protein markers Bax/Bcl2, activated caspase
3 and poly (ADP-ribose) polymerase-1 (PARP-1) in the cortex and hippocampus
regions of the LPS-treated adult rat brain. In addition, the morphological
results of the fluoro-jade B (FJB) and Nissl staining showed that LiCl attenuated
the neuronal degeneration in the cortex and hippocampus regions of the LPS
treated adult rat brain. Taken together, our Western blot and morphological
results indicated that LiCl significantly prevents the LPS-induced neurotoxicity
via attenuation of neuroinflammation and apoptotic neurodegeneration in the
cortex and hippocampus of the adult rat brain.
PMID- 28511951
TI - Proteome profiling reveals immune responses in Japanese flounder (Paralichthys
olivaceus) infected with Edwardsiella tarda by iTRAQ analysis.
AB - The liver is an important organ for bacterial pathogen attack in fish. The
differential proteomic response of the Japanese flounder liver to Edwardsiella
tarda infection was examined using isobaric tags for relative and absolute
quantitation (iTRAQ) labeling followed by liquid chromatography-tandem mass
spectrometry (LC-MS/MS). A total of 3290 proteins were identified and classified
into categories related to biological process (51.4%), molecular function
(63.6%), and cellular component (57.7%). KEGG enrichment analysis indicated the
complement and coagulation cascade pathways and the mineral absorption pathway
were significantly enriched. Among the differentially expressed proteins, those
involved in mediating complement cascade (e.g. complement component C7, C8, C9,
complement factor H, complement factor Bf/C2) and mineral absorption (e.g.
ferritin, STEAP-4) were most significantly upregulated during infection.
Subsequently, five significantly upregulated (C4, C8beta, ferritin middle
subunit, PRDX4-like and KRT18) and one significantly downregulated (transferrin)
candidate immune proteins were validated by multiple reaction monitoring (MRM)
assays. Furthermore, changes in expression of 15 proteins in the complement
cascade and mineral absorption pathways were validated at the transcriptional
level using quantitative real-time PCR (qPCR). The transcriptional levels of four
transcription factors (p21Ras, Rab-31-like, NF-kappaB, STAT3) were also
investigated by qPCR following infection with E. tarda. This study contributes to
understanding the defense mechanisms of the liver in fish.
PMID- 28511954
TI - High intensity interval training (HIIT) improves resting blood pressure,
metabolic (MET) capacity and heart rate reserve without compromising cardiac
function in sedentary aging men.
AB - BACKGROUND: This study examined a programme of pre-conditioning exercise with
subsequent high intensity interval training (HIIT) on blood pressure,
echocardiography, cardiac strain mechanics and maximal metabolic (MET) capacity
in sedentary (SED) aging men compared with age matched masters athletes (LEX).
METHODS: Using a STROBE compliant observational design, 39 aging male
participants (SED; n=22, aged 62.7+/-5.2yrs) (LEX; n=17, aged=61.1+/-5.4yrs) were
recruited to a study that necessitated three distinct assessment phases;
enrolment (Phase A), following pre-conditioning exercise in SED (Phase B), then
following 6weeks of HIIT performed once every five days by both groups before
reassessment (Phase C). Hemodynamic, echocardiographic and cardiac strain
mechanics were obtained at rest and maximal cardiorespiratory and chronotropic
responses were obtained at each measurement phase. RESULTS: The training
intervention improved systolic, mean arterial blood pressure, rate pressure
product and heart rate reserve (each P<0.05) in SED and increased MET capacity in
both SED and LEX (P<0.01) which was amplified by HIIT. Echocardiography and
cardiac strain measures were unremarkable apart from trivial increase to intra
ventricular septum diastole (IVSd) (P<0.05) and decrease to left ventricular
internal dimension diastole (LVId) (P<0.05) in LEX following HIIT. CONCLUSIONS: A
programme of preconditioning exercise with HIIT induces clinically relevant
improvements in blood pressure, rate pressure product and encourages recovery of
heart rate reserve in SED, while improving maximal MET capacity in both SED and
LEX without inducing any pathological cardiovascular remodeling. These data add
to the emerging repute of HIIT as a safe and promising exercise prescription to
improve cardiovascular function and metabolic capacity in sedentary aging.
PMID- 28511955
TI - Chronic Diarrhea Caused by Chronic Lymphocytic Leukemia and Small Lymphocytic
Lymphoma With Colorectal Involvement.
PMID- 28511953
TI - Small conductance Ca2+-activated K+ channels in the plasma membrane, mitochondria
and the ER: Pharmacology and implications in neuronal diseases.
AB - Ca2+-activated K+ (KCa) channels regulate after-hyperpolarization in many types
of neurons in the central and peripheral nervous system. Small conductance Ca2+
activated K+ (KCa2/SK) channels, a subfamily of KCa channels, are widely
expressed in the nervous system, and in the cardiovascular system. Voltage
independent SK channels are activated by alterations in intracellular Ca2+
([Ca2+]i) which facilitates the opening of these channels through binding of Ca2+
to calmodulin that is constitutively bound to the SK2 C-terminus. In neurons, SK
channels regulate synaptic plasticity and [Ca2+]i homeostasis, and a number of
recent studies elaborated on the emerging neuroprotective potential of SK channel
activation in conditions of excitotoxicity and cerebral ischemia, as well as
endoplasmic reticulum (ER) stress and oxidative cell death. Recently, SK channels
were discovered in the inner mitochondrial membrane and in the membrane of the
endoplasmic reticulum which sheds new light on the underlying molecular
mechanisms and pathways involved in SK channel-mediated protective effects. In
this review, we will discuss the protective properties of pharmacological SK
channel modulation with particular emphasis on intracellularly located SK
channels as potential therapeutic targets in paradigms of neuronal dysfunction.
PMID- 28511956
TI - Erosion of the Duodenum by an Aortic Graft, Leading to Recurrent Sepsis.
PMID- 28511957
TI - A stochastic vector-borne epidemic model: Quasi-stationarity and extinction.
AB - We consider a stochastic model describing the spread of a vector borne disease in
a community where individuals (hosts and vectors) die and new individuals (hosts
and vectors) are born. The time to extinction of the disease, TQ, starting in
quasi-stationary (conditional on non extinction) is studied. Properties of the
limiting distribution are used to obtain an approximate expression for E(TQ), the
mean-parameter in the exponential distribution of the time to extinction, for a
finite population. It is then investigated numerically and by means of
simulations how E(TQ) and its approximations depend on the different model
parameters.
PMID- 28511958
TI - Selection of discriminant mid-infrared wavenumbers by combining a naive Bayesian
classifier and a genetic algorithm: Application to the evaluation of
lignocellulosic biomass biodegradation.
AB - Infrared spectroscopy provides useful information on the molecular compositions
of biological systems related to molecular vibrations, overtones, and
combinations of fundamental vibrations. Mid-infrared (MIR) spectroscopy is
sensitive to organic and mineral components and has attracted growing interest in
the development of biomarkers related to intrinsic characteristics of
lignocellulose biomass. However, not all spectral information is valuable for
biomarker construction or for applying analysis methods such as classification.
Better processing and interpretation can be achieved by identifying
discriminating wavenumbers. The selection of wavenumbers has been addressed
through several variable- or feature-selection methods. Some of them have not
been adapted for use in large data sets or are difficult to tune, and others
require additional information, such as concentrations. This paper proposes a new
approach by combining a naive Bayesian classifier with a genetic algorithm to
identify discriminating spectral wavenumbers. The genetic algorithm uses a linear
combination of an a posteriori probability and the Bayes error rate as the
fitness function for optimization. Such a function allows the improvement of both
the compactness and the separation of classes. This approach was tested to
classify a small set of maize roots in soil according to their biodegradation
process based on their MIR spectra. The results show that this optimization
method allows better discrimination of the biodegradation process, compared with
using the information of the entire MIR spectrum, the use of the spectral
information at wavenumbers selected by a genetic algorithm based on a classical
validity index or the use of the spectral information selected by combining a
genetic algorithm with other methods, such as Linear Discriminant Analysis. The
proposed method selects wavenumbers that correspond to principal vibrations of
chemical functional groups of compounds that undergo degradation/conversion
during the biodegradation of lignocellulosic biomass.
PMID- 28511959
TI - Pattern formation in a nonlocal mathematical model for the multiple roles of the
TGF-beta pathway in tumour dynamics.
AB - The growth and invasion of cancer cells are very complex processes, which can be
regulated by the cross-talk between various signalling pathways, or by single
signalling pathways that can control multiple aspects of cell behaviour. TGF-beta
is one of the most investigated signalling pathways in oncology, since it can
regulate multiple aspects of cell behaviour: cell proliferation and apoptosis,
cell-cell adhesion and epithelial-to-mesenchimal transition via loss of cell
adhesion. In this study, we use a mathematical modelling approach to investigate
the complex roles of TGF-beta signalling pathways on the inhibition and growth of
tumours, as well as on the epithelial-to-mesenchimal transition involved in the
metastasis of tumour cells. We show that the nonlocal mathematical model derived
here to describe repulsive and adhesive cell-cell interactions can explain the
formation of new tumour cell aggregations at positions in space that are further
away from the main aggregation. Moreover, we show that the increase in cell-cell
adhesion leads to fewer but larger aggregations, and the increase in TGF-beta
molecules - whose late-stage effect is to decrease cell adhesion - leads to many
small cellular aggregations. Finally, we perform a sensitivity analysis on some
parameters associated with TGF-beta dynamics, and use it to investigate the
relation between the tumour size and its metastatic spread.
PMID- 28511960
TI - Inadequate target volume delineation and local-regional recurrence after
intensity-modulated radiotherapy for human papillomavirus-positive oropharynx
cancer.
AB - PURPOSE: To perform a spatial analysis of local-regional recurrences, in relation
to quantitative dose distribution, among patients treated by intensity-modulated
radiotherapy (IMRT) for human papillomavirus (HPV)-positive oropharyngeal cancer.
METHODS AND MATERIALS: The records of 107 consecutive patients who presented for
consideration of re-irradiation for local-regional recurrent disease occurring in
a previously irradiated field were reviewed. The original IMRT plans were
retrieved for those with HPV-positive disease originating from the oropharynx,
and deformable image registration was used to fuse the magnetic resonance imaging
(MRI) and positron emission tomography (PET) scans obtained at recurrence to the
pre-treatment planning computed tomography (CT) dataset. The recurrent tumor
volume (Vrecur) was subsequently identified on axial imaging, and the dose of
radiation received by Vrecur was then calculated and analyzed using dose-volume
histograms. RESULTS: A total of 83 recurrent lesions occurring in 50
oropharyngeal cancer patients were HPV-positive and met inclusion criteria. Using
PET-defined Vrecur, thirty-three lesions were classified as in-field recurrences
(40%), 35 were marginal misses (41%), and 15 were true misses (18%). Using the
MRI-defined Vrecur, thirty-seven lesions were classified as in-field recurrences
(45%), 32 were marginal misses (39%), and 14 were true misses (17%). CONCLUSION:
A significant proportion of local-regional recurrences from HPV-positive
oropharyngeal cancer represented geographical misses which possibly could have
been prevented with more meticulous attention to IMRT planning. This finding has
important implications with respect to ongoing attempts to de-escalate radiation
dose for this disease. Our data highlight the importance of robust quality
assurance with careful review of target volumes prior to the initiation of IMRT.
PMID- 28511961
TI - Pre-Operative Evaluation of Axillary Lymph Node Status in Patients with Suspected
Breast Cancer Using Shear Wave Elastography.
AB - The aim of this study was to evaluate shear wave elastography (SWE) for pre
operative evaluation of axillary lymph node (LN) status in patients with
suspected breast cancer. A total of 130 axillary LNs in 130 patients who
underwent SWE before fine-needle aspiration, core biopsy or surgery were
analyzed. On gray-scale images, long and short axes, shape (elliptical or round),
border (sharp or unsharp) and cortical thickening (concentric, eccentric or no
fatty hilum) of LNs were assessed. On SWE, mean, maximum, minimum, standard
deviation and the lesion-to-fat ratio (Eratio) values of elasticity were
collected. Gray-scale and SWE features were compared statistically between
metastatic and benign LNs using the chi2-test and independent t-test. Diagnostic
performance of each feature was evaluated using the area under the receiver
operating characteristic curve (AUC). Logistic regression analysis was used to
determine gray-scale or SWE features independently associated with metastatic
LNs. Of the 130 LNs, 65 (50%) were metastatic and 65 (50%) were benign after
surgery. Metastatic LNs were significantly larger (p = 0.018); had higher
elasticity indexes at SWE (p < 0.0001); and had higher proportions of round shape
(p = 0.033), unsharp border (p = 0.048) and eccentric cortical thickening or no
fatty hilum (p = 0.005) compared with benign LNs. On multivariate analysis,
Eratio was independently associated with metastatic LNs (odds ratio = 3.312, p =
0.008). Eratio had the highest AUC among gray-scale (0.582-0.719) and SWE (0.900
0.950) variables. SWE had good diagnostic performance in metastatic axillary LNs,
and Eratio was independently associated with metastatic LNs.
PMID- 28511962
TI - Interventions for prevention of type 2 diabetes in relatives: A systematic
review.
AB - The relatives and partners of people with type 2 diabetes are at increased risk
of developing type 2 diabetes. This systematic review examines randomized
controlled trials, written in English that tested an intervention, which aimed to
modify behaviors known to delay or prevent type 2 diabetes, among the relatives
or partners of people with type 2 diabetes. Study quality was assessed using the
Cochrane Collaboration's tool for assessing risk of bias. Seven studies met the
inclusion criteria. The majority of studies were at low risk of bias. Six studies
tested an intervention in first-degree relatives of people with type 2 diabetes
and one in partners. Intervention components and intervention intensity across
studies varied, with those targeting diet and physical activity reporting the
most significant changes in primary outcomes. Only one study did not observe
significant changes in primary outcomes. There were three main recruitment
approaches: advertising in the community, recruiting people through their
relatives with diabetes, or identifying people as high risk by screening of their
own health care contacts. Some evidence was found for potentially successful
interventions to prevent type 2 diabetes among the relatives and partners of
people with type 2 diabetes, although finding simple and effective methods to
identify and recruit them remains a challenge. Future studies should explore the
effect of patients' perceptions on their family members' behavior and capitalize
on family relationships in order to increase intervention effectiveness.
PMID- 28511964
TI - Evidence on multimorbidity from definition to intervention: An overview of
systematic reviews.
AB - The increasing challenge of multiple chronic diseases (multimorbidity) requires
more evidence-based knowledge and effective practice. In order to better
understand the existing evidence on multimorbidity, we performed a systematic
review of systematic reviews on multimorbidity with pre-established search
strategies and exclusion criteria by searching multiple databases and grey
literature. Of 8006 articles found, 53 systematic reviews (including meta
analysis and qualitative research synthesis performed in some reviews) that
stated multimorbidity as the main focus were included, with 79% published during
2013-2016. Existing evidence on definition, measurement, prevalence, risk
factors, health outcomes, clinical practice and medication (polypharmacy), and
intervention and management were identified and synthesised. There were three
major definitions from three perspectives. Seven studies on prevalence reported a
range from 3.5% to 100%. As six studies showed, depression, hypertension,
diabetes, arthritis, asthma, and osteoarthritis were prone to be comorbid with
other conditions. Four groups of risk factors and eight multimorbidity associated
outcomes were explored by five and six studies, respectively. Nine studies
evaluated interventions, which could be categorized into either organizational or
patient-oriented, the effects of these interventions were varied. Self-management
process, priority setting and decision making in multimorbidity were synthesised
by evidence from 4 qualitative systematic reviews. We were unable to draw solid
conclusions from this overview due to the heterogeneity in methodology and
inconsistent findings among included reviews. As suggested by all included
studies, there is a need for prospective research, especially longitudinal cohort
studies and randomized control trials, to provide more definitive evidence on
multimorbidity.
PMID- 28511963
TI - Short interfering RNA targeting Net1 reduces the angiogenesis and tumor growth of
in vivo cervical squamous cell carcinoma through VEGF down-regulation.
AB - Net1, a guanine nucleotide exchange factor, is implicated in cancer cell invasion
through activation of RhoA. However, there is still no report on the association
between Net1 and cancer angiogenesis. The current study was designed to explore
the role of Net1 in the angiogenesis of cervical squamous cell carcinoma (CSCC)
and further observe the effects of Net1 short interfering RNA (siRNA) on the
tumor growth. Net1 was overexpressed in CSCC samples (n=80), correlated with the
cancer microvessel density (r=0.223, P=.026), and related to aggressive clinical
behaviors, including depth of cervical wall invasion (P=.041), parametrial
involvement (P=.037), lymph node metastasis (P=.021), and vascular invasion
(P=.018). Human umbilical vein endothelial cells treated with supernatant of SiHa
cells with Net1 siRNA showed significantly decreased proliferation (0.75+/-0.038
versus 1.0+/-0.015, P<.001), migration (39.3+/-6.5 versus 66.0+/-10.1, P=.019),
and tube formation (13.5+/-3.05 versus 21.7+/-2.89, P=.030) compared with those
human umbilical vein endothelial cells treated with normal SiHa cells
supernatant. Net1 siRNA of SiHa decreased VEGF expression level (0.60+/-0.026
versus 0.78+/-0.031, P=.02). Furthermore, Net1 siRNA significantly reduced tumor
growth (P=.037) and microvessel density (5.8+/-0.43 versus 3.4+/-0.55, P=.012)
and decreased the expression level of VEGF (0.31+/-0.002 versus 0.39+/-0.004,
P<.001) in CSCC. In conclusion, Net1 promotes the angiogenesis of CSCC, and siRNA
targeting Net1 can effectively reduce the angiogenesis and thus inhibit the tumor
growth of CSCC in vivo.
PMID- 28511965
TI - Relationship between hospital volume and outcomes in patients with traumatic
brain injury: A retrospective observational study using a national inpatient
database in Japan.
AB - BACKGROUND: The relationship between hospital volume and outcome after traumatic
brain injury (TBI) is not completely understood in a real clinical setting. We
investigated whether patients admitted with TBI achieved better outcomes in high
volume hospitals than in low-volume hospitals using a national inpatient database
in Japan. METHODS: This retrospective cohort study used the Diagnosis Combination
Procedure database in Japan. We included patients with TBI admitted to hospitals
with a Japan Coma Scale (JCS) score >=2 between April 1, 2013 and March 31, 2014.
Hospital volume was defined as the annual number of all admissions with TBI in
individual hospitals. The hospital volume was categorized into four volume
groups: low (<=60 admissions per hospital), medium-low (61-120 admissions per
hospital), medium-high (121-180 admissions per hospital) and high (>=181
admissions per hospital). The outcomes of interest included 28-day mortality and
survival discharge with complete dependency defined as a Barthel Index score of 0
at discharge. We used multivariate logistic regression models fitted with
generalized estimating equations to evaluate relationships between the hospital
volume and the outcomes. The hospital volume was evaluated both as categorical
variables defined above and as continuous variables. RESULTS: The analysis
dataset consisted of 20,146 eligible patients. Of these, 2,784 died within 28days
(13.8%) and 3,409 were completely dependent among 16,996 patients discharged
alive (20.1%). Multivariate analyses found that there was no significant
difference between the high-volume and low-volume groups for 28-day mortality
(adjusted odds ratio [OR] 0.79, 95% confidence interval [CI] 0.58-1.06 for the
high-volume group) or complete dependency at discharge (adjusted OR 0.94, 95% CI
0.71-1.23 for the high-volume group). The results were the same when the hospital
volume was evaluated as a continuous variable. CONCLUSIONS: Hospital volume did
not appear to influence outcomes in patients with TBI. High-volume hospitals may
not be necessarily beneficial for patients with TBI exhibiting impaired
consciousness as a whole.
PMID- 28511967
TI - A sliding hip screw augmented with 2 screws is biomechanically similar to an
inverted triad of cannulated screws in repair of a Pauwels type-III fracture.
AB - OBJECTIVE: Pauwels III femoral neck fractures are highly unstable. These
fractures are commonly treated with three cannulated screws or sliding hip screw
(SHS) implants, however high rates of non-union persist. A hybrid SHS construct
has recently been proposed. The objective of the study was to compare this
construct to the familiar inverted triad of cannulated screws and to a single
SHS. METHODS: Fourth generation biomechanical femur analogs were used to create a
highly repeatable injury model. The hybrid SHS construct contained a SHS with two
superior cannulated screws in an inverted triangle configuration. Eight samples
for each construct were biomechanically evaluated and the results compared using
ANOVA (p<0.05). RESULTS: The cannulated triad and hybrid SHS provided similar
stiffness and fracture gap motion. The single SHS exhibited significantly lower
stiffness and larger fracture plane diastasis than either the inverted triangle
of cannulated screws or hybrid SHS (p<0.05). None of the constructs exhibited
catastrophic failure during cyclic loading nor under loading up to 2.5 times body
weight. CONCLUSIONS: The single SHS provided the least stable fracture fixation,
while the inverted triad and hybrid SHS constructs were mechanically similar. The
fracture repair simulated here illustrates how these repairs have the potential
to return near pre-fracture strength in ideal conditions with young, healthy
bone. However; in clinical situations where comminution impairs load transfer
through the cortices the hybrid SHS may be the most favorable option.
PMID- 28511966
TI - Identification of potential target genes and related regulatory transcription
factors in spontaneous hairline fracture induced by hypervitaminosis A.
AB - BACKGROUND: The aim was to research the molecular changes of bone cells induced
by excessive dose of vitamin A, and analyze molecular mechanism underlying
spontaneous fracture. METHODS: The gene expression profile of GSE29859, including
4 cortical bone marrow samples with excessive doses of Vitamin A and 4 control
cortical bone marrow samples, was obtained from the Gene Expression Omnibus (GEO)
database. Differentially expressed genes (DGEs) between cortical bone marrow
samples and control samples were screened out and pathway enrichment analysis was
undertaken. Based on the MSigDB database, the potential regulatory transcription
factors (TFs) were identified. RESULTS: A total of 373 DEGs including 342 up- and
31 down-regulated genes were identified. These DEGs were significantly enriched
in pathways of protein processing in endoplasmic reticulum, ubiquitin mediated
proteolysis and glycerophospholipid metabolism. Finally, the most significant
regulatory TFs were obtained, including E2F Transcription Factor 1 (E2F1), GA
Binding Protein Transcription Factor (GABP), Nuclear Factor, Erythroid 2-Like 2
(NRF2) and ELK1, Member of ETS Oncogene Family (ELK1). CONCLUSION: Key TFs
including E2F1, GABP, NRF2 and ELK1 and their targets genes such as Ube2d3, Uba1,
Phb2 and Tomm22 may play potential key roles in spontaneous fracture induced by
hypervitaminosis A. The pathways of protein processing in endoplasmic reticulum,
ubiquitin mediated proteolysis and glycerophospholipid metabolism may be key
mechanisms involved in spontaneous fracture induced by hypervitaminosis A. Our
findings will provide new insights for the target selection in clinical
application to prevent spontaneous fracture induced by hypervitaminosis A.
PMID- 28511968
TI - The Future of Image-guided Radiotherapy.
PMID- 28511969
TI - The current role of decompressive craniectomy for severe traumatic brain injury.
AB - There is little doubt that decompressive craniectomy can reduce mortality
however, the results of a recent study has provided more evidence to inform the
debate regarding clinical and ethical concerns that it merely converts death into
survival with severe disability or in a vegetative state. The recently published
RESCUEicp trial compared last-tier secondary decompressive craniectomy with
continued medical management for refractory intracranial hypertension after
severe traumatic brain injury. Patients were randomly assigned to decompressive
craniectomy with medical therapy or to receive continued medical therapy with the
option of adding barbiturates. The results of the study support the findings of
the stroke studies in that the reduction in mortality was almost directly
translatable into survival with either severe disability or in a vegetative
state. The question remains as to whether there is a subset of patients who
obtain benefit from surgical decompression and it is in this regard that the use
of observational cohort studies and sophisticated outcome prediction models may
be of use. Comparing the percentage prediction with the observed long outcome
provides an objective assessment of the most likely outcome can be obtained for
patients thought to require surgical intervention. Whilst there will always be
limitations when using this type of data they may help prompt appropriate patient
centred discussions regarding realistic outcome expectations. A broader debate is
also needed regarding use of a medical intervention that may leave a person in a
condition that they may feel to be unacceptable and also places a considerable
burden on society.
PMID- 28511970
TI - Cleomedes of Astypalaea: A possible early sufferer of chronic traumatic
encephalopathy.
AB - Dementia pugilistica was the term adopted by H. Martland in 1928 to identify
boxers with cognitive decline. In more recent years, the syndrome of dementia
pugilistica with pathological correlates has been defined as chronic traumatic
encephalopathy (CTE). A number of sportsmen have been recently diagnosed with
CTE; and we may have identified an ancient Greek athlete of pankration who
presented with the symptoms that have been associated with CTE. Our study reports
the history and the known clinical information about Cleomedes of Astypalaea,
possibly the first athlete ever affected by CTE.
PMID- 28511971
TI - Learning curve for the endoscopic endonasal approach for suprasellar
craniopharyngiomas.
AB - The endoscopic endonasal approach is considered an alternative minimally invasive
approach for suprasellar craniopharyngiomas. However, the complicated surgical
manipulations required by this approach have limited its application. We evaluate
whether the approach features a learning curve. Thirty-three patients were
retrospectively reviewed and grouped as early (17 patients) and late (16 patient)
groups. The operation time, extent of removal, ophthalmology, endocrinology,
reconstruction and modifications of standard technique were evaluated. Between
the two groups, the operation time decreased from 201.1+/-105.3min in the early
group to 107.6+/-90.0min in the late group (p<0.05). Regarding clinical outcomes,
non-significantly increasing trends toward the rate of gross total resection,
visual improvement and (from 76.5% to 87.5%, 73.3% to 93.3%), significantly
decreasing trends toward the rate of tumor recurrence (from 23.5% to 0% p<0.05)
and non-significantly decreasing trends toward the rate of hypopituitarism
recovery (26.7% to 0%) were observed between the two groups. With respect to
complications, non-statistically significant decreasing trends toward transient
cranial nerve paralysis (from 5.9% to 0%) and non-statistically significant
increasing trends toward rate of CSF leakage, meningitis and new hypothyroidism
(from 11.8% to 25%, 11.8% to 31.3%, 0 to 3%) were observed. We identified a
learning curve for the endoscopic endonasal approach for suprasellar
craniopharyngiomas. The exact number of patients necessary to establish a
significant improvement in the clinical outcomes and decrease in the
complications warrants further investigation. The outcomes of tumor recurrence
may be associated with duration of follow-up. The CSF leakage represented the
most common complication.
PMID- 28511972
TI - A matched cohort comparison of cervical disc arthroplasty versus anterior
cervical discectomy and fusion: Evaluating perioperative outcomes.
AB - OBJECTIVE: Cervical disc arthroplasty (CDA) is a recent alternative to anterior
cervical discectomy and fusion (ACDF) in patients suffering cervical disc
herniation and degeneration. To date, a systematic analysis of their comparative
advantages and risks following elective surgery remains elusive. METHODS: Adult
patients undergoing elective CDA or ACDF were extracted from the American College
of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database
years 2011-2014. A total of 19,369 patients were matched 1:1 by age, sex,
functional status, charlson comorbidity index, ASA classification, BMI
classification, and number of vertebral levels operated on during surgery. This
matching process led to a final sample of 588 subjects (294 CDA, 294 ACDF).
Multivariable regression was performed for five outcome measures: operation time,
early complications, reoperation rates, hospital length of stay (HLOS), and
discharge destination. Mean differences (B), odds ratios (OR) and associated 95%
confidence intervals (CI) are reported. RESULTS: Compared to ACDF, CDA was
associated with decreased mean operation time (B=-18.78-min, 95% CI [-29.13,
8.42]; p<0.001), decreased HLOS (B=-0.44-days [-0.77, -0.11]; p=0.009), and
increased likelihood of discharge to home (OR=5.39 [1.14-25.43]; p=0.033). No
differences in reoperation rates and complications were found. CONCLUSION: In a
matched cohort analysis, CDA performs comparably to ACDF and is associated with
decreased operation time and HLOS, and increased likelihood of discharge to home,
without differences in 30-day complications or reoperation rates. Future
prospective studies are warranted.
PMID- 28511973
TI - Anterior decompression and hybrid reconstruction with titanium mesh cage plus
plate and self-locking stand-alone cage for the treatment of three-level cervical
spondylotic myelopathy.
AB - It has been reported that anterior cervical decompression has good clinical
outcomes for the treatment of adjacent three-level cervical spondylotic
myelopathy (CSM). However, the application of a long plate in the anterior
cervical spine poses substantial risks of soft tissue damage. In this
retrospective study, we aimed to analyze the clinical and radiological results of
the hybrid construction with titanium mesh cage (TMC) plus plate and self-locking
stand-alone cage for treatment of adjacent three-level CSM. A total of 28
consecutive patients with adjacent three-level CSM were treated by anterior
decompression and hybrid reconstruction with TMC plus plate and self-locking
stand-alone cage. Clinical outcomes, complications, fusion rate and time, cage
subsidence and spinal curvature were assessed. The mean follow-up period was
22.8months. The average operative time was 103+/-18.5min, and the average blood
loss was 115+/-13.3mL. The JOA score and degree of spinal curvature were
significantly increased at the final follow-up compared with preoperatively
(P<0.05). Twenty-seven cases finally achieved a solid fusion, and the average
time to achieve a solid fusion was 6.2months. Postoperative complications
included one case of cerebrospinal fluid leakage (3.57%), one case of temporary
sore throat (3.57%) and two cases of TMC subsidence (7.1%). No dysphagia and
hoarseness were observed. Anterior decompression and hybrid reconstruction with
TMC plus plate and self-locking stand-alone cage could be used safely and
effectively for the treatment of adjacent three-level CSM. It could effectively
restore cervical lordosis, reduce the complications related to long plate
fixation, and lead to satisfactory outcomes.
PMID- 28511974
TI - Risk factor analysis for meralgia paresthetica: A hospital-based study in Taiwan.
AB - Recognizing the cause is essential for the management of meralgia paresthetica
(MP), also known as lateral femoral cutaneous neuropathy. The aim of this study
was to investigate the etiologies of MP and their influence on each other. This
retrospective study enrolled referral patients with electromyographic studies who
fulfilled the clinical and electrodiagnostic criteria of MP from January 2003 to
December 2013. Data including age, gender, body weight, body height, occupation,
and relevant medical history were collected. The etiological analysis was based
on age and gender. A total of 50 patients (30 males and 20 females) were
enrolled. The average age (+/-standard deviation) at diagnosis was 49.8+/
12.8years. Risk factors were identified in 29 cases (58.0%). More patients
younger than 50years of age were male (73.1%, p=0.049). Peaks of age occurred
between 41-50years in men and 51-60years in women. More males had a body mass
index>=24kg/m2 (69.2% vs. 31.6%, p=0.012) and >=27kg/m2 (34.6% vs. 0.0%,
p=0.006). Overweight and obese patients were more vulnerable to occupational
factors (50.0% vs. 19.0%, p=0.030). Only one case had diabetes mellitus (2%).
Male middle-aged patients with a higher body mass index and certain occupations
had an increased risk of MP. In contrast to the peak age distribution of the male
patients, the frequency of developing MP was relatively even among the women at
all ages. The cause was often obscure.
PMID- 28511975
TI - Leptomeningeal failure in patients with breast cancer receiving stereotactic
radiosurgery for brain metastases.
AB - PURPOSE: Prior studies suggest a high incidence of leptomeningeal failure (LMF)
in breast cancer metastatic to brain. This study examines breast cancer-specific
variables affecting development of LMF and survival after Gamma-Knife
Radiosurgery (GKS). METHODS: Between 2000-2010, 149 (breast) and 658 other
histology patients were treated with GKS. Hormone/HER2, age, local/distant brain
failure, prior craniotomy, and prior whole-brain radiotherapy (WBRT) were
assessed. Median follow-up was 54months (range, 0-106). Serial MRI determined
local and distant-brain failure and LMF. Statistical analysis with
categorical/continuous data comparisons were done with Fisher's-exact, Wilcoxon
rank-sum, log-rank tests, and Cox-Proportional Hazard models. RESULTS: Of 149
patients, 21 (14%) developed LMF (median time of 11.9months). None of the
following predicted for LMF: Her2-status (HR=0.49, p=0.16), hormone-receptor
status (HR=1.15, p=0.79), prior craniotomy (HR=1.58, p=0.42), prior WBRT
(HR=1.36, p=0.55). Non-significant factors between patients that did (n=21) and
did not (n=106) develop LMF included neurologic death (p=0.34) and median
survival (8.6 vs 14.2months, respectively). Breast patients who had distant
failure after GKS (65/149; 43.6%) were more likely to later develop LMF (HR 4.2,
p=0.005); including 15/65 (23%) patients who had distant-failure and developed
LMF. Median time-to-death for patients experiencing LMF was 6.1months (IQR 3.4
7.8) from onset of LMF. Median survival from LMF to death was much longer in
breast (6.1months) than in other (1.7months) histologies CONCLUSION: Breast
cancer patients had a longer survival after diagnosis of LMF versus other
histologies. Neither ER/PR/HER2 status, nor prior surgery or prior WBRT predicted
for development of LMF in breast patients.
PMID- 28511976
TI - Fertility, pregnancy, and prolactinoma: A survey of pituitary surgeons' view and
review of the literature.
AB - OBJECTIVE: Pituitary surgeons frequently encounter female prolactinoma patients
seeking treatment to restore fertility. Current medical guidelines recommend
using dopamine agonist (DA) for this, but for fetal safety, DA should stop upon
pregnancy confirmation. The probability that prolactinoma may grow during
pregnancy makes this last recommendation imperfect. With the advances in
endoscopic surgery, we queried the potential role for surgery in these infertile
patients, who may be ambivalent about both stopping and continuing DA while
pregnant. METHODS: An anonymous survey was sent to pituitary surgeons to
investigate how they would advise prolactinoma patients on treatment of
infertility, and counsel them about pregnancy. Directories from various US-based
neurosurgical societies were culled. Surgeons who designated themselves as "skull
base"/"pituitary" were surveyed. RESULTS: Seventy-six surgeons responded (41%).
The majority (67%) adhered to medical guidelines for microprolactinoma, but 26%
recommended surgery. However, for a macroprolactinoma at diagnosis, the number of
surgeons who recommended DA treatment vs. surgical treatment were almost evenly
split (chi2p=0.06). The practice setting of a multidisciplinary clinic with
endocrinologists did not significantly influence our respondents' choice. For a
patient who presented after becoming pregnant on DA, our respondents were against
surgery to prevent tumor growth (96%). CONCLUSION: A review of the current
literature shows that both medical and surgical therapy have flaws. Significant
numbers of surgeons considered surgery a legitimate option for prolactinoma
patients seeking to be pregnant. The divergence between these surgeons' opinion
and current medical guidelines warrants further investigation and discussion.
PMID- 28511977
TI - Role of acetylcholine and serotonin in novelty processing using an oddball
paradigm.
AB - The processing of novel stimuli is known to take place in the hippocampus and
frontal cortex, and is influenced by the cholinergic system. This ability is
crucial to help detect changes in the environment and adapt behaviour
accordingly. Previous research has shown that acetylcholine (ACh) can interact
with serotonin (5-HT) at the hippocampal level, which may have consequences for
cognitive functioning. However, little is known about the exact nature of this
ACh and 5-HT interaction as well their possible interactive effects on novelty
processing. We investigated the interactive role of ACh and 5-HT in novelty
processing in healthy young participants. Levels of these neurotransmitters were
manipulated with the muscarinic M1 antagonist biperiden, and with acute
tryptophan depletion (ATD). Participants received either placebo, biperiden, ATD,
or a combination of both in a double-blind cross-over design. Auditory event
related potentials (ERPs) were recorded while a novelty oddball task was
presented. Our results showed that biperiden affected ERP components considered
to reflect attentional mechanisms; it increased the P50 amplitude and decreased
that of the P200. Furthermore, a decrease of N100 amplitude by ATD was reversed
by biperiden. The treatments did not affect the mismatch negativity (MMN)
component, which is elicited when a deviant stimulus is presented in a sequence
of repetitive stimuli. Importantly, biperiden decreased the amplitude of the ERP
component related to novelty processing (P3a). The current study's results did
not reveal an interactive effect of ACh and 5-HT on novelty processing. However,
the data do suggest that ACh is involved in novelty processing and that it
influences basic stimulus processing, without affecting sound-discrimination
accuracy.
PMID- 28511978
TI - Behavioural outcomes of adult female offspring following maternal stress and
perinatal fluoxetine exposure.
AB - : Depression, anxiety, and stress are common in pregnant women. One of the
primary pharmacological treatments for anxiety and depression is the
antidepressant fluoxetine (Flx). Maternal stress, depression, and Flx exposure
are known to effect neurodevelopment of the offspring, however, their combined
effects have been scarcely studied, especially in female offspring. The present
study investigated the combined effects of maternal stress during pregnancy and
perinatal exposure to Flx on the behaviour of female mice as adults. METHODS:
Mouse dams were exposed to either chronic unpredictable stress (embryonic (E) day
7 to E18), or FLX (E15- postnatal day 12), or a combination of stress and FLX or
left untreated. At two months of age, the female offspring went through a
comprehensive behavioural test battery. RESULTS: Maternal stress led to increased
activity and alterations of prepulse inhibition in the adult female offspring.
Maternal treatment with Flx had a potentially beneficial effect on spatial
memory. The combination of prenatal stress and perinatal Flx exposure did not
interact in their effects. These results suggest that gestational Flx exposure
may have a limited negative impact on female offspring.
PMID- 28511979
TI - Water and T-maze protocols are equally efficient methods to assess spatial memory
in 3xTg Alzheimer's disease mice.
AB - Rodent spatial memory is commonly tested using the water-maze; however, there is
a potential confound of stress on learning in this behavioural paradigm. This is
particularly relevant when testing spatial memory in models of neurodegeneration,
such as the 3xTg mouse model for Alzheimer's disease. Here, we first confirmed
that 3xTgAD mice express fear conditioning and then compared the performance of
young and middle-aged mice on short-duration versions of the radial arm water
maze (RAWM) and the minimally stressful T-maze spontaneous alternation task. Our
main questions were: (1) does the reliance on stressors in water-maze training
mask the true cognitive ability of 3xTgAD mice; and (2) are 3xTgAD mice similarly
impaired in water-maze and T-maze protocols. Firstly, male and female 3xTgAD mice
displayed intact freezing responses in both contextual and Pavlovian fear
conditions. As male 3xTgAD mice displayed relatively enhanced fear responses the
remaining tests were performed using only female 3xTgAD and control mice in order
to equate for response to stressors. We found that alternation rates after both
short and long delays were impaired at both ages in female 3xTgAD mice,
indicative of robust spatial working memory deficits. For RAWM, again performance
deficits were found in young 3xTgAD mice. As both tasks had similar efficacy at
revealing early spatial memory deficits, we suggest that spontaneous behavioural
protocols be prioritised over water maze testing in models such the 3xTgAD mouse
as the former provide a far less stressful but equally effective alternative.
PMID- 28511980
TI - Reward loss and the basolateral amygdala: A function in reward comparisons.
AB - The neural circuitry underlying behavior in reward loss situations is poorly
understood. We considered two such situations: reward devaluation (from large to
small rewards) and reward omission (from large rewards to no rewards). There is
evidence that the central nucleus of the amygdala (CeA) plays a role in the
negative emotion accompanying reward loss. However, little is known about the
function of the basolateral nucleus (BLA) in reward loss. Two hypotheses of BLA
function in reward loss, negative emotion and reward comparisons, were tested in
an experiment involving pretraining excitotoxic BLA lesions followed by training
in four tasks: consummatory successive negative contrast (cSNC), autoshaping (AS)
acquisition and extinction, anticipatory negative contrast (ANC), and open field
testing (OF). Cell counts in the BLA (but not in the CeA) were significantly
lower in animals with lesions vs. shams. BLA lesions eliminated cSNC and ANC, and
accelerated extinction of lever pressing in AS. BLA lesions had no effect on OF
testing: higher activity in the periphery than in the central area. This pattern
of results provides support for the hypothesis that BLA neurons are important for
reward comparison. The three affected tasks (cSNC, ANC, and AS extinction)
involve reward comparisons. However, ANC does not seem to involve negative
emotions and it was affected, whereas OF activity is known to involve negative
emotion, but it was not affected. It is hypothesized that a circuit involving the
thalamus, insular cortex, and BLA is critically involved in the mechanism
comparing current and expected rewards.
PMID- 28511981
TI - Role of cholinergic receptors in memory retrieval depends on gender and age of
memory.
AB - The phenomenon of utilizing information acquired in the past to make decision and
performance in present depends on memory retrieval, which is affected in
retrograde amnesia. Role of cholinergic receptors in memory retrieval is not much
explored. In this study we evaluated the gender specific role of cholinergic
receptors, i.e. muscarinic and nicotinic receptors, in memory retrieval in young
Balb/c mice. Acute (only one injection, 30min before test) and sub-chronic (five
days) muscarinic blockade (using scopolamine=1mg/kg) before test impaired
retrieval of contextual fear memory in male (31.45+/-5.39% and 33.36+/-3.78%
respectively) and female mice (22.88+/-5.73%; P<0.05), except sub-chronically
treated female group (33.31+/-4.90%; P>0.05). Only sub-chronic nicotinic receptor
antagonism (using methyllycaconitine MLA=87.5MUg/kg and dihydro beta erythroidine
DHbetaE=1mg/kg) in female showed significantly higher freezing response than
control during contextual fear memory retrieval (60.85+/-7.71% and 40.91+/-7.53%
respectively; P<0.001). Acute and sub-chronic muscarinic antagonism (but not
nicotinic antagonism) impaired spatial memory retrieval in male (P<0.05) but not
in female mice (P>0.05). There was no effect of acute and sub-chronic cholinergic
receptor antagonism on discriminating novel object from the familiar one in male
and female mice, however, nicotinic receptor blockade affected the working memory
of all male and female mice on test day compared to the training sessions. Our
results suggested that cholinergic receptors involvement in retrieving spatial
and fear memories depends on the age of the memory and gender.
PMID- 28511983
TI - Target temperature management after cardiac arrest in comatose survivors in
Brazil - A survey of the current clinical practice.
PMID- 28511982
TI - Characteristic and intermingled neocortical circuits encode different visual
object discriminations.
AB - Synaptic plasticity and neural network theories hypothesize that the essential
information for advanced cognitive tasks is encoded in specific circuits and
neurons within distributed neocortical networks. However, these circuits are
incompletely characterized, and we do not know if a specific discrimination is
encoded in characteristic circuits among multiple animals. Here, we determined
the spatial distribution of active neurons for a circuit that encodes some of the
essential information for a cognitive task. We genetically activated protein
kinase C pathways in several hundred spatially-grouped glutamatergic and
GABAergic neurons in rat postrhinal cortex, a multimodal associative area that is
part of a distributed circuit that encodes visual object discriminations. We
previously established that this intervention enhances accuracy for specific
discriminations. Moreover, the genetically-modified, local circuit in POR cortex
encodes some of the essential information, and this local circuit is
preferentially activated during performance, as shown by activity-dependent gene
imaging. Here, we mapped the positions of the active neurons, which revealed that
two image sets are encoded in characteristic and different circuits. While
characteristic circuits are known to process sensory information, in sensory
areas, this is the first demonstration that characteristic circuits encode
specific discriminations, in a multimodal associative area. Further, the circuits
encoding the two image sets are intermingled, and likely overlapping, enabling
efficient encoding. Consistent with reconsolidation theories, intermingled and
overlapping encoding could facilitate formation of associations between related
discriminations, including visually similar discriminations or discriminations
learned at the same time or place.
PMID- 28511985
TI - Reply to: Time matters in patients undergoing extracorporeal cardiopulmonary
resuscitation.
PMID- 28511984
TI - Comparison of three cognitive exams in cardiac arrest survivors.
AB - BACKGROUND: Cognitive deficits may detract from quality of life after cardiac
arrest. Their pattern and prevalence are not well documented. We used the
Computer Assessment of Mild Cognitive Impairment (CAMCI), the Montreal Cognitive
Assessment (MOCA) and the 41 Cent Test (41CT) to assess cognitive impairment in
cardiac arrest survivors and examine the exams' diagnostic accuracy. We
hypothesized that the scores of these exams would indicate the presence of
cognitive impairment in arrest survivors, that the overall scores on the three
study assessments would correlate with one another, and that the 41CT, MOCA, and
executive function element of the CAMCI would vary independently from other non
executive CAMCI components, reflecting executive function impairment after
cardiac arrest. METHODS: Four researchers administered the CAMCI, MOCA, and/or
the 41CT to cardiac arrest survivors after discharge from the intensive care unit
between 2010 and 2015. Physicians screened patients with the Mini-Mental State
Exam to determine when this cognitive testing was feasible, generally when the
patient was able to score 20-25 points on the MMSE. We performed pairwise
correlations between the different subscales' and tests' scores. RESULTS: One
hundred and fourteen participants completed the CAMCI, of which 38 (33.3%)
participants additionally completed the MOCA and 41CT. The median (IQR)
percentile score for CAMCI for all 114 participants was 33.5 (18.3, 49.8), which
corresponds to moderately low risk of impairment. The median (IQR) for the MOCA
was 22.0 (19, 24.8) out of a possible 30, which is considered indicative of
abnormal cognitive function, and for the 41CT was 6 (5, 7) out of a possible 7
points when all 38 participants were included. MOCA correlated strongly with the
overall CAMCI score (r=0.71); the CAMCI correlated moderately strongly with the
41CT (r=0.62) and the MOCA and 41CT were moderately strongly correlated with each
other (r=0.56). When all 114 CAMCI scores were considered, the Executive Accuracy
subscale was strongly correlated with the overall CAMCI score (r=0.81).
CONCLUSION: The CAMCI detects cognitive impairment after cardiac arrest. The MOCA
correlates strongly with the overall CAMCI and the executive function subscale of
the CAMCI. The 41CT as appears less effective than the MOCA in detecting
cognitive deficits.
PMID- 28511987
TI - Human parechovirus type 3 infection: An emerging infection in neonates and young
infants.
AB - Human parechoviruses (HPeVs) are RNA viruses that have characteristics similar to
those of enteroviruses and usually cause mild respiratory or gastrointestinal
symptoms. Human parechovirus type 3 (HPeV3), first reported in 2004, is
exceptional because it can provoke sepsis and meningoencephalitis leading to
neurological sequelae, and even death, in neonates and young infants.
Pediatricians and researchers are increasingly aware that HPeV3 is responsible
for serious disease in neonates and young infants. Retrospective studies and
several reports of epidemics of HPeV3 infection have provided data on
epidemiology, clinical symptoms and signs, laboratory findings, and outcomes.
However, the pathogenesis of HPeV3 infection remains unclear, which explains the
lack of specific antiviral therapy and effective prevention measures. Maternal
antibodies are important in protection against severe HPeV3-related disease, and
this may be a clue regarding its pathogenesis. HPeV3 epidemics are likely to
continue, and because the clinical manifestations of HPeV3 are severe,
determining the pathogenesis of HPeV3 infection and establishing specific
antiviral therapies are important goals for future research.
PMID- 28511986
TI - Epileptiform discharge detection with the 4-channel frontal
electroencephalography during post-resuscitation care.
AB - INTRODUCTION: We performed this study to investigate whether the SEDline system,
a 4-channel-processed electroencephalography (EEG) monitoring device in the
frontal area, can detect epileptiform discharges accurately during post
resuscitation care in comatose cardiac arrest survivors. METHODS: Adult comatose
cardiac arrest survivors, who were admitted to the intensive care unit (ICU) for
post-resuscitation care including TTM, were enrolled. Within 72h post-return of
spontaneous circulation (ROSC), conventional EEG was conducted for 30min. The
SEDline system data were recorded with a video camera simultaneously with
conventional EEG. Data retrieved from conventional EEG were interpreted by a
neurologist and data from the SEDline system were interpreted by three emergency
physicians blinded to the conventional EEG data. Then, the sensitivity,
specificity, positive predictive value (PPV), negative predictive value (NPV),
and accuracy of the SEDline system to detect epileptiform discharges were
calculated. RESULTS: Thirty-nine patients were enrolled in this study.
Epileptiform discharges were confirmed in 6 patients (15.4%) who had the same
patterns of generalized periodic epileptiform discharges in both conventional EEG
and the concurrent SEDline system. The SEDline system showed 100.0% (95%
confidence interval (CI), 54.1-100.0%) of sensitivity, 100.0% (95% CI, 89.4
100.0%) of specificity, 100.0% (95% CI, 54.1-100.0%) of PPV, and 100.0% (95% CI,
89.4-100.0%) of NPV. The overall classification accuracy of the SEDline system to
detect epileptiform discharges was 100.0%. CONCLUSION: The SEDline system
detected epileptiform discharges accurately in comatose cardiac arrest survivors
during post-resuscitation care.
PMID- 28511988
TI - Exploring the Potential of Nanotherapeutics in Targeting Tumor Microenvironment
for Cancer Therapy.
AB - Advanced research in the field of cancer biology clearly demonstrated the key
role of tumor microenvironment (TME) in cancer development and metastasis
particularly in solid tumors. Components of TME, being non-neoplastic in nature
provide supportive and permissive conditions for the growth of cancer cells.
Hence it is important to modify TME in cancer therapy and this would be achieved
by better understanding of TME morphological features and functioning of stromal
components. Nanotechnology based drug delivery offers various advantages such as
prolonged circulation time, delivery of cargo at desired site, improved
bioavailability, reduced toxicity etc. over conventional chemotherapeutics.
Abnormal characteristic features of TME play a paradoxical role in
nanoparticulate drug delivery. Leaky vasculature, acidic and hypoxic conditions
of TME helps in the accumulation of tailored nanoparticles whereas high
interstitial pressure and dense stroma restrict the extravasation, homogenous
distribution of nanocarriers in TME. This review mainly discusses the potential
of nanotherapeutics in targeting TME by briefly discussing stromal components,
therapeutic opportunities and barriers offered by TME for nanoparticulate drug
delivery. Updated information on TME remodeling strategies for improved drug
delivery and specific targeting of individual stromal components are also
outlined.
PMID- 28511990
TI - Corrigendum to "Inhibition of autophagy enhances hydroquinone-induced TK6 cell
death" [Toxicol. in Vitro 41 (2017) 123-132].
PMID- 28511989
TI - Biased agonism/antagonism at the AngII-AT1 receptor: Implications for adrenal
aldosterone production and cardiovascular therapy.
AB - Many of the effects of angiotensin II (AngII), including adrenocortical
aldosterone release, are mediated by the AngII type 1 receptor (AT1R), a receptor
with essential roles in cardiovascular homeostasis. AT1R belongs to the G protein
coupled receptor (GPCR) superfamily, mainly coupling to the Gq/11 type of G
proteins. However, it also signals through betaarrestins, oftentimes in parallel
to eliciting G protein-dependent signaling. This has spurred infinite
possibilities for cardiovascular pharmacology, since various beneficial effects
are purportedly exerted by AT1R via betaarrestins, unlike AT1R-induced G protein
mediated pathways that usually result in damaging cardiovascular effects,
including hypertension and aldosterone elevation. Over the past decade however, a
number of studies from our group and others have suggested that AT1R-induced
betaarrestin signaling can also be damaging for the heart, similarly to the G
protein-dependent one, with regard to aldosterone regulation. Additionally, AT1R
induced betaarrestin signaling in astrocytes from certain areas of the brain may
also play a significant role in central regulation of blood pressure and
hypertension pathogenesis. These findings have provided the impetus for testing
available angiotensin receptor blockers (ARBs) in their efficacy towards blocking
both routes (i.e. both G protein- and betaarrestin-dependent) of AT1R signaling
in vitro and in vivo and also have promoted structure-activity relationship (SAR)
studies for the AngII molecule in terms of betaarrestin signaling to certain
cellular effects, e.g. adrenal aldosterone production. In the present review, we
will recount all of these recent studies on adrenal and astrocyte AT1R-dependent
betaarrestin signaling while underlining their implications for cardiovascular
pathophysiology and therapy.
PMID- 28511991
TI - Calculation of the cross-sectional shape of a fibril from equatorial scattering.
AB - An alternate formulation of helical diffraction theory is used to generate cross
sectional shapes of fibrous structures from equatorial scattering. We demonstrate
this approach with computationally generated scattering intensities and then
apply it to scattering data from Tobacco Mosaic Virus (TMV) and in vitro
assembled fibrils of Abeta40 peptides. Refining the cross-sectional shape of TMV
from SAXS data collected on a 26mg/ml solution resulted in a circular shape with
outer diameter of ~180A and inner diameter of ~40A consistent with the known
structure of TMV. We also utilized this method to analyze the equatorial
scattering from TMV collected by Don Caspar from a concentrated (24% ~295mg/ml)
gel of TMV as reported in his Ph.D. thesis in 1955. This data differs from the
SAXS data in having a sharp interference peak at ~250A spacing, indicative of
strong interparticle interactions in the gel. Analysis of this data required
consideration of interatomic vectors as long as 2000A and resulted in generation
of images that were interpreted as representative of local organization of TMV
particles in the sample. Peaks in the images were separated, on average by about
250A with a density consistent with Caspar's original measurements. Analysis of
SAXS data from Abeta fibrils resulted in a cross-sectional shape that could be
interpreted in terms of structural models that have been constructed from ssNMR
and cryoEM. These results demonstrate an unexpected use of the small-angle region
of fiber diffraction patterns to derive fundamental structural properties of
scattering objects.
PMID- 28511992
TI - RNA-seq analyses reveal that cervical spinal cords and anterior motor neurons
from amyotrophic lateral sclerosis subjects show reduced expression of
mitochondrial DNA-encoded respiratory genes, and rhTFAM may correct this
respiratory deficiency.
AB - Amyotrophic lateral sclerosis (ALS) is a generally fatal neurodegenerative
disease of adults that produces weakness and atrophy due to dysfunction and death
of upper and lower motor neurons. We used RNA-sequencing (RNA-seq) to analyze
expression of all mitochondrial DNA (mtDNA)-encoded respiratory genes in ALS and
CTL human cervical spinal cords (hCSC) and isolated motor neurons. We analyzed
with RNA-seq mtDNA gene expression in human neural stem cells (hNSC) exposed to
recombinant human mitochondrial transcription factor A (rhTFAM), visualized in 3
dimensions clustered gene networks activated by rhTFAM, quantitated their
interactions with other genes and determined their gene ontology (GO) families.
RNA-seq and quantitative PCR (qPCR) analyses showed reduced mitochondrial gene
expression in ALS hCSC and ALS motor neurons isolated by laser capture
microdissection (LCM), and revealed that hNSC and CTL human cervical spinal cords
were similar. Rats treated with i.v. rhTFAM showed a dose-response increase in
brain respiration and an increase in spinal cord mitochondrial gene expression.
Treatment of hNSC with rhTFAM increased expression of mtDNA-encoded respiratory
genes and produced one major and several minor clusters of gene interactions.
Gene ontology (GO) analysis of rhTFAM-stimulated gene clusters revealed
enrichment in GO families involved in RNA and mRNA metabolism, suggesting
mitochondrial-nuclear signaling. In postmortem ALS hCSC and LCM-isolated motor
neurons we found reduced expression of mtDNA respiratory genes. In hNSC's rhTFAM
increased mtDNA gene expression and stimulated mRNA metabolism by unclear
mechanisms. rhTFAM may be useful in improving bioenergetic function in ALS.
PMID- 28511993
TI - The expression of opioid genes in non-classical reward areas depends on early
life conditions and ethanol intake.
AB - The young brain is highly sensitive to environmental influences that can cause
long-term changes in neuronal function, possibly through altered gene expression.
The endogenous opioid system continues to mature after birth and because of its
involvement in reward, an inadequate maturation of this system could lead to
enhanced susceptibility for alcohol use disorder. Recent studies show that the
classical reward areas nucleus accumbens and ventral tegmental area are less
affected by early life stress whereas endogenous opioids in non-classical areas,
e.g. dorsal striatum and amygdala, are highly responsive. The aim was to
investigate the interaction between early life conditions and adult voluntary
ethanol intake on opioid gene expression. Male Wistar rats were exposed to
conventional rearing, 15, or 360min of daily maternal separation (MS) postnatal
day 1-21, and randomly assigned to ethanol or water drinking postnatal week 10
16. Rats exposed to early life stress (MS360) had increased opioid receptor gene
(Oprm1, Oprd1 and Oprk1) expression in the dorsal striatum. Ethanol drinking was
associated with lower striatal Oprd1 and Oprk1 expression solely in rats exposed
to early life stress. Furthermore, rats exposed to early life stress had high
inherent Pomc expression in the amygdala but low expression after ethanol intake.
Thus, adverse events early in life induced changes in opioid gene expression and
also influenced the central molecular response to ethanol intake. These long-term
consequences of early life stress can contribute to the enhanced risk for
excessive ethanol intake and alcohol use disorder seen after exposure to
childhood adversity.
PMID- 28511994
TI - Study of rubella candidate vaccine based on a structurally modified plant virus.
AB - A novel rubella candidate vaccine based on a structurally modified plant virus -
spherical particles (SPs) - was developed. SPs generated by the thermal
remodelling of the tobacco mosaic virus are promising platforms for the
development of vaccines. SPs combine unique properties: biosafety, stability,
high immunogenicity and the effective adsorption of antigens. We assembled in
vitro and characterised complexes (candidate vaccine) based on SPs and the
rubella virus recombinant antigen. The candidate vaccine induced a strong humoral
immune response against rubella. The IgG isotypes ratio indicated the
predominance of IgG1 which plays a key role in immunity to natural rubella
infection. The immune response was generally directed against the rubella antigen
within the complexes. We suggest that SPs can act as a platform (depot) for the
rubella antigen, enhancing specific immune response. Our results demonstrate that
SPs-antigen complexes can be an effective and safe candidate vaccine against
rubella.
PMID- 28511995
TI - Live, full-term mouse pups from oocytes grown and matured in vitro with serum
substitutes.
AB - For in vitro growth and maturation of mouse oocytes (IVG-IVM), serum is added to
media up to and including the stage of oocyte maturation; this subsequently
supports oocytes through fertilization and early embryo development. However,
problems may occur with sera, such as batch differences and issues of biosafety.
The purpose of the present study was to determine the capacity for fertilization
and pre- and post-implantation development of oocytes that underwent IVG-IVM with
a serum substitute. Oocyte-granulosa cell complexes from preantral follicles were
cultured in medium with either fetal bovine serum (FBS), Serum Substitute
SupplementTM (SSS), or KnockoutTM Serum Replacement (KSR) for 10days, and were
then allowed to mature for 17 h. Subsequently, more than 90% of oocytes underwent
germinal vesicle breakdown (GVBD) and more than 70% reached metaphase II, with no
significant difference between the groups. A lower fertilization rate, presumably
due to zona hardening, was found in the serum substitute groups. Nevertheless,
more than 50% of the inseminated oocytes were fertilized and 35%-45% of them
underwent first cleavage and developed to the blastocyst stage. Following embryo
transfer, one and four live offspring were produced from the SSS and KSR groups,
respectively. The present study demonstrated that murine IVG-IVM oocytes cultured
in media with a serum substitute, achieved fertilization in vitro, pre- and post
implantation development, and the delivery of live pups, although the efficiency
of the process is reduced compared to FBS supplementation.
PMID- 28511996
TI - Comparative characteristics of spermatozoa harvested and cryopreserved in culture
and cryoprotectant media with or without donor serum proteins.
AB - The objectives of this study is to evaluate the efficacy of protein-free media in
the preparation, holding and crypreservation of spermatazoa for use in ART.
Normozoospermic semen samples (N=71) were used to compare the effects of media on
the survival and quality of spermatozoa when washed and cultured with different
media with and without added proteins at 4 degrees C, 15 degrees C, 22 degrees C
and 37 degrees C for 0, 4-7 and 24h. Survival and quality of spermatozoa were
assessed after freeze-thaw with synthetic cryoprotectant with and without
proteins. Ethics/IRB approval was obtained (Ref. 1073.52). Spermatozoa parameters
were similar in all media after washing and culture for 24h. Post-thaw survival
and quality of spermatozoa was not significantly different 24h after thawing of
samples frozen in all cryoprotectant medium. In conclusion synthetic protein-free
culture and cryoprotectant media are equal in efficacy to protein-containing
media in culture and cryopreservation of spermatozoa . Use of these synthetic
media are anticipated to significantly reduce the risk, potentially associated
with conventional protein-containing media, of transmission of disease and
possibly harmful undeclared proteins to the patient, baby and the healtcare
worker. Synthetic media also ensure consistency of quality between batches of
media.
PMID- 28511997
TI - Thorough QT (TQT) studies: concordance with torsadogenesis and an evolving
cardiac safety testing paradigm.
AB - Since 2005, when the International Conference on Harmonisation (ICH) E14
guideline was adopted, no drug has been withdrawn because of QTc prolongation or
torsade de pointes arrhythmia. There are, however, costs associated with this
success. In addition to the time and money invested, thorough QT (TQT) studies
have limited the efficiency of the drug development pipeline. In this paper, we
discuss the relevance of TQT trials as a tool for proarrhythmic risk prediction
as a part of the debate regarding their usefulness.
PMID- 28511999
TI - Clinical nutrition education in medical schools: Results of an ESPEN survey.
PMID- 28511998
TI - A J-shaped association between soy food intake and depressive symptoms in Chinese
adults.
AB - BACKGROUND & AIMS: Soy food has been proven to have multiple positive effects on
human health, however, no study has yet investigated the association between
habitual intake of soy food and depressive symptoms in general population. The
objective of this study was to examine this association. METHODS: In a cross
sectional analysis, we studied a sample of 13,760 adults (mean age 43.5 years) in
Tianjin, China. The Self-Rating Depression Scale (SDS) was used to assess
depressive symptoms, with four cut-off points (SDS >=40, 45, 48 or 50) indicating
increased level of depressive symptoms. Food Frequency Questionnaire (FFQ) was
used to assess dietary intake. RESULTS: In the total population, the prevalence
of increased depressive symptoms was 7.2% (SDS >=50). Comparing to the group with
lowest intake frequency of soy food (=twice/day. Associations remained when other cut-off points (SDS >=40, 45 or 48)
were used as a definition of increased depressive symptoms. CONCLUSION: Findings
from this study suggested a J-shaped association between intake frequency of soy
food and incidence of depressive symptoms among adults. For the first time, the
study provides evidence that light-to-moderate intake of soy food may reduce the
incidence of depressive symptoms, while relatively high (>=twice/day) intake may
generate the opposite effect.
PMID- 28512000
TI - Computed tomography (CT)-compatible remote center of motion needle steering
robot: Fusing CT images and electromagnetic sensor data.
AB - Lung cancer is the most common cause of cancer-related death, and early detection
can reduce the mortality rate. Patients with lung nodules greater than 10 mm
usually undergo a computed tomography (CT)-guided biopsy. However, aligning the
needle with the target is difficult and the needle tends to deflect from a
straight path. In this work, we present a CT-compatible robotic system, which can
both position the needle at the puncture point and also insert and rotate the
needle. The robot has a remote-center-of-motion arm which is achieved through a
parallel mechanism. A new needle steering scheme is also developed where CT
images are fused with electromagnetic (EM) sensor data using an unscented Kalman
filter. The data fusion allows us to steer the needle using the real-time EM
tracker data. The robot design and the steering scheme are validated using three
experimental cases. Experimental Case I and II evaluate the accuracy and CT
compatibility of the robot arm, respectively. In experimental Case III, the
needle is steered towards 5 real targets embedded in an anthropomorphic gelatin
phantom of the thorax. The mean targeting error for the 5 experiments is 1.78 +/-
0.70 mm. The proposed robotic system is shown to be CT-compatible with low
targeting error. Small nodule size and large needle diameter are two risk factors
that can lead to complications in lung biopsy. Our results suggest that nodules
larger than 5 mm in diameter can be targeted using our method which may result in
lower complication rate.
PMID- 28512003
TI - Towards a sustainable biobased industry - Highlighting the impact of
extremophiles.
AB - The transition of the oil-based economy towards a sustainable economy completely
relying on biomass as renewable feedstock requires the concerted action of
academia, industry, politics and civil society. An interdisciplinary approach of
various fields such as microbiology, molecular biology, chemistry, genetics,
chemical engineering and agriculture in addition to cross-sectional technologies
such as economy, logistics and digitalization is necessary to meet the future
global challenges. The genomic era has contributed significantly to the
exploitation of natures biodiversity also from extreme habitats. By applying
modern technologies it is now feasible to deliver robust enzymes (extremozymes)
and robust microbial systems that are active at temperatures up to 120 degrees C,
at pH 0 and 12 and at 1000bar. In the post-genomic era, different sophisticated
"omics" analyses will allow the identification of countless novel enzymes
regardless of the lack of cultivability of most microorganisms. Furthermore,
elaborate protein-engineering methods are clearing the way towards tailor-made
robust biocatalysts. Applying environmentally friendly and efficient biological
processes, terrestrial and marine biomass can be converted to high value products
e.g. chemicals, building blocks, biomaterials, pharmaceuticals, food, feed and
biofuels. Thus, further application of extremophiles has the potential to improve
sustainability of existing biotechnological processes towards a greener biobased
industry.
PMID- 28512005
TI - Intraosseous venous drainage anomaly at the tibia.
PMID- 28512001
TI - Low dose inflammatory potential of silica particles in human-derived THP-1
macrophage cell culture studies - Mechanism and effects of particle size and
iron.
AB - Silica and iron are major constituents in ambient particulate matter, and iron is
a common impurity in many engineered nanomaterials. The purpose of this work was
to determine the pro-inflammatory and other biological effects and mechanism of
particle size and iron presence under low dose, non-cytotoxic conditions that are
likely to approximate actual exposure levels, in contrast with higher dose
studies in which cytotoxicity occurs. Specifically, human-derived THP-1
macrophages were exposed to 1 MUg/ml of pristine and iron-coated 50 nm and 2 MUm
engineered silica nanoparticles. Particles were first characterized for size,
size distribution, surface area, iron concentration, phase and aggregation in
cell culture media. Then, biological assays were conducted to determine a non
lethal dose used in subsequent experiments. Superoxide production, lipid
peroxidation, and increased pro-inflammatory cytokine (TNF-alpha and IL-1beta)
mRNA expression were measured as a function of particle size and iron presence.
Smaller particle size and the presence of iron increased superoxide production,
lipid peroxidation, and the induction of pro-inflammatory cytokine mRNA
expression. Separate addition of an iron-chelator, a scavenger of superoxide and
hydrogen peroxide, and an inhibitor of phosphatidylcholine specific phospholipase
C (PC-PLC), suppressed the increase in cytokine mRNA expression. Furthermore,
free iron itself showed none of the aforementioned effects. The results highlight
the importance of particle size and iron in lung inflammation for both natural
and engineered nanomaterials, under low dose, non-toxic conditions, and support
the role of an oxidant, lipid peroxidation and PC-PLC dependent inflammatory
mechanism.
PMID- 28512006
TI - Stress fracture in athletes.
AB - Stress fractures are widely encountered in sport medicine and rheumatology.
Stress fractures result from abnormal and repetitive loading on normal bone that
lead to microdamage and then fracture. They occur after sudden increase in
physical activity. They appear mostly at lower limbs. Women are at higher risk
than men. Patients complain of mechanical pain. Clinical findings include focused
pain and sometimes swelling. No biological test is useful for diagnosis. Plain
radiographs are normal in early stage disease. MRI is the gold standard to
confirm stress fracture. Treatments of stress fracture always involve rest and
analgesics. Non-steroidal anti-inflammatory should be use cautiously because they
may inhibit callus formation. Extracorporeal shockwave may be a new approach for
SF not healing with rest. Surgical treatment is often needed in high risk stress
fracture of delayed healing, non-union or complete fracture.
PMID- 28512002
TI - Cell-surface G-protein-coupled receptors for tumor-associated metabolites: A
direct link to mitochondrial dysfunction in cancer.
AB - Mitochondria are the sites of pyruvate oxidation, citric acid cycle, oxidative
phosphorylation, ketogenesis, and fatty acid oxidation. Attenuation of
mitochondrial function is one of the most significant changes that occurs in
tumor cells, directly linked to oncogenesis, angiogenesis, Warburg effect, and
epigenetics. In particular, three mitochondrial enzymes are inactivated in
cancer: pyruvate dehydrogenase (PDH), succinate dehydrogenase (SDH), and 3
hydroxy-3-methylglutaryl CoA synthase-2 (HMGCS2). These enzymes are subject to
regulation via acetylation/deacetylation. SIRT3, the predominant mitochondrial
deacetylase, directly targets these enzymes for deacetylation and maintains their
optimal catalytic activity. SIRT3 is a tumor suppressor, and deacetylation of
these enzymes contributes to its biological function. PDH catalyzes the oxidative
decarboxylation of pyruvate into acetyl CoA, SDH oxidizes succinate into
fumarate, and HMGCS2 controls the synthesis of the ketone body beta
hydroxybutyrate. As the activities of these enzymes are decreased in cancer,
tumor cells accumulate lactate and succinate but produce less amounts of beta
hydroxybutyrate. Apart from their role in cellular energetics, these metabolites
function as signaling molecules via specific cell-surface G-protein-coupled
receptors. Lactate signals via GPR81, succinate via GPR91, and beta
hydroxybutyrate via GPR109A. In addition, lactate activates hypoxia-inducible
factor HIF1alpha and succinate promotes DNA methylation. GPR81 and GPR91 are
tumor promoters, and increased production of lactate and succinate as their
agonists drives tumorigenesis by enhancing signaling via these two receptors. In
contrast, GPR109A is a tumor suppressor, and decreased synthesis of beta
hydroxybutyrate as its agonist suppresses signaling via this receptor, thus
attenuating the tumor-suppressing function of GPR109A. In parallel with the
opposing changes in lactate/succinate and beta-hydroxybutyrate levels, tumor
cells upregulate GPR81 and GPR91 but downregulate GPR109A. As such, these three
metabolite receptors play a critical role in cancer and represent a new class of
drug targets with selective antagonists of GPR81 and GPR91 for cancer treatment
and agonists of GPR109A for cancer prevention.
PMID- 28512004
TI - Contribution of high resolution peripheral quantitative CT to the management of
bone and joint diseases.
AB - Many imaging modalities have been described to diagnose and monitor osteoporosis
(OP), osteoarthritis and inflammatory rheumatic diseases. Over the last ten
years, High Resolution peripheral Quantitative Computerized Tomography (HR-pQCT)
was shown to be a precise and non invasive technique to study bone and joint
diseases in clinical research. It allows the study of both cortical and
trabecular bone microarchitecture at the distal tibia and radius, and further
applications have been developed such as the study of mechanical properties by
the finite element analysis. Thus, in case-control and cross-sectional studies,
microarchitecture parameters discriminated fractured individuals independently of
areal BMD. Also, microstructure parameters can predict incident fracture in
postmenopausal women. In metabolic diseases associated with bone fragility, HR
pQCT may also be used to explore bone changes. In joint disease studies, HR-pQCT
was a remarkable tool to assess bone erosion and joint space narrowing at the
hand. This article gives an overview of this imaging technique.
PMID- 28512007
TI - Antimalarial drug retinopathy: A typical " Bull's eyes " appearance of fundus.
PMID- 28512008
TI - 3D printing and modelling of customized implants and surgical guides for non
human primates.
AB - BACKGROUND: Primate neurobiologists use chronically implanted devices such as
pedestals for head stabilization and chambers to gain access to the brain and
study its activity. Such implants are skull-mounted, and made from a hard,
durable material, such as titanium. NEW METHOD: Here, we present a low-cost
method of creating customized 3D-printed cranial implants that are tailored to
the anatomy of individual animals. We performed pre-surgical computed tomography
(CT) and magnetic resonance (MR) scans to generate three-dimensional (3D) models
of the skull and brain. We then used 3D modelling software to design implantable
head posts, chambers, and a pedestal anchorage base, as well as craniotomy guides
to aid us during surgery. Prototypes were made from plastic or resin, while
implants were 3D-printed in titanium. The implants underwent post-processing and
received a coating of osteocompatible material to promote bone integration.
RESULTS: Their tailored fit greatly facilitated surgical implantation, and
eliminated the gap between the implant and the bone. To date, our implants remain
robust and well-integrated with the skull. COMPARISON WITH EXISTING METHOD(S):
Commercial-off-the-shelf solutions typically come with a uniform, flat base,
preventing them from sitting flush against the curved surface of the skull. This
leaves gaps for fluid and tissue ingress, increasing the risk of microbial
infection and tissue inflammation, as well as implant loss. CONCLUSIONS: The use
of 3D printing technology enabled us to quickly and affordably create unique,
complex designs, avoiding the constraints levied by traditional production
methods, thereby boosting experimental success and improving the wellbeing of the
animals.
PMID- 28512009
TI - Combining D-cycloserine with appetitive extinction learning modulates amygdala
activity during recall.
AB - Appetitive Pavlovian conditioning plays a crucial role in the pathogenesis of
drug addiction and conditioned reward cues can trigger craving and relapse even
after long phases of abstinence. Promising preclinical work showed that the NMDA
receptor partial agonist D-cycloserine (DCS) facilitates Pavlovian extinction
learning of fear and drug cues. Furthermore, DCS-augmented exposure therapy seems
to be beneficial in various anxiety disorders, while the supposed working
mechanism of DCS during human appetitive or aversive extinction learning is still
not confirmed. To test the hypothesis that DCS administration before extinction
training improves extinction learning, healthy adults (n=32) underwent
conditioning, extinction, and extinction recall on three successive days in a
randomized, double-blind, placebo-controlled fMRI design. Monetary wins and
losses served as unconditioned stimuli during conditioning to probe appetitive
and aversive learning. An oral dose of 50mg of DCS or placebo was administered 1h
before extinction training and DCS effects during extinction recall were
evaluated on a behavioral and neuronal level. We found attenuated amygdala
activation in the DCS compared to the placebo group during recall of the
extinguished appetitive cue, along with evidence for enhanced functional amygdala
vmPFC coupling in the DCS group. While the absence of additional physiological
measures of conditioned responses during recall in this study prevent the
evaluation of a behavioral DCS effect, our neuronal findings are in accordance
with recent theories linking successful extinction recall in humans to modulatory
top-down influences from the vmPFC that inhibit amygdala activation. Our results
should encourage further translational studies concerning the usefulness of DCS
to target maladaptive Pavlovian reward associations.
PMID- 28512010
TI - Cerebellar learning modulates surface expression of a voltage-gated ion channel
in cerebellar cortex.
AB - Numerous experiments using ex vivo electrophysiology suggest that mammalian
learning and memory involves regulation of voltage-gated ion channels in terms of
changes in function. Yet, little is known about learning-related regulation of
voltage-gated ion channels in terms of changes in expression. In two experiments,
we examined changes in cell surface expression of the voltage-gated potassium
channel alpha-subunit Kv1.2 in a discrete region of cerebellar cortex after
eyeblink conditioning (EBC), a well-studied form of cerebellar-dependent
learning. Kv1.2 in cerebellar cortex is expressed almost entirely in basket
cells, primarily in the axon terminal pinceaux (PCX) region, and Purkinje cells,
primarily in dendrites. Cell surface expression of Kv1.2 was measured using both
multiphoton microscopy, which allowed measurement confined to the PCX region, and
biotinylation/western blot, which measured total cell surface expression. In the
first experiment, rats underwent three sessions of EBC, explicitly unpaired
stimulus exposure, or context-only exposure and the results revealed a decrease
in Kv1.2 cell surface expression in the unpaired group as measured with
microscopy but no change as measured with western blot. In the second experiment,
the same three training groups underwent only one half of a session of training,
and the results revealed an increase in Kv1.2 cell surface expression in the
unpaired group as measured with western blot but no change as measured with
microscopy. In addition, rats in the EBC group that did not express conditioned
responses (CRs) exhibited the same increase in Kv1.2 cell surface expression as
the unpaired group. The overall pattern of results suggests that cell surface
expression of Kv1.2 is changed with exposure to EBC stimuli in the absence, or
prior to the emergence, of CRs.
PMID- 28512011
TI - Modulation of alpha oscillations is required for the suppression of semantic
interference.
AB - Recent findings on alpha band oscillations suggest their important role in memory
consolidation and suppression of external distractors such as environmental
noise. However, less attention was given to the phenomenon of internal
distracting information being solely inherent to the stimuli content. Human
memory may be prone to internal distractions caused by semantic relatedness
between the meaning of words (e.g., atom, neutron, nucleus, etc.) to be encoded,
i.e., semantic interference. Our study investigates the brain oscillatory
dynamics behind the semantic interference phenomenon, whose possible outcome is
known as false memories. In this direction, Deese-Roediger-McDermott word lists
were appropriated for a modified Sternberg paradigm in auditory modality.
Participants received semantically related and unrelated word lists via
headphones while EEG data were acquired. Semantic interference triggered the
false memory rates to be higher than those of other types of memory errors.
Analysis demonstrated that the upper part of alpha band (~10-12Hz) power
decreases on parieto-occipital channels in the retention interval, prior to the
probe item for semantically related condition. Our study elucidates the
oscillatory mechanisms behind semantic interference by relying on alpha
functional inhibition theory.
PMID- 28512012
TI - Crustins are distinctive members of the WAP-containing protein superfamily: An
improved classification approach.
AB - Crustins are considered effector molecules of innate immunity in arthropods, and
classification schemes have been proposed over the last 10 years. However,
classification problems have emerged: for example, proteins that have been well
identified as members of a particular category have also been classified as
crustins. Therefore, the objective of this manuscript was to analyze and, based
on solid arguments, improve the original proposed nomenclature to make crustins a
distinctive group of antibacterial proteins. The presence of WAP or 4DSC domain
has been considered a distinctive feature of crustins; however, several
antibacterial proteins containing WAP domains have been detected in diverse
taxonomic groups (including mammals). Here, we present evidence supporting the
idea that the Cys-rich region and the 4DSC domain can be considered a signature
of crustins and, together with some distance arrangements occurring within this
12-Cys region, yield enough information for the classification of these proteins.
Herein, the core characteristics to be considered for classification purposes are
the length of the Gly-rich region and the repetitive tetrapeptides occurring
within this region; these characteristics are then hierarchically followed by the
F and A distances located within the 4DSC domain. Finally, the proposed system
considers the crustin signature as the common structure in all members, which is
a differentiator from other proteins containing WAP domains, separating crustins
as a well-distinguished member of the superfamily of WAP-domain containing
proteins.
PMID- 28512013
TI - Evaluation of the N-latex serum free light chain assay on the Siemens BNII
analyzer and agreement with The Binding Site FreeLite assay on the SPAPlus.
AB - OBJECTIVES: To evaluate the Siemens N-latex kappa free light chain (kappaFLC) and
lambda FLC (lambdaFLC) assays on the BNII nephelometer and assess agreement with
The Binding Site Freelite FLC assays on the SPAPlus. DESIGN AND METHODS: Over 180
patient serum samples from routine analysis of kappaFLC and lambdaFLC measured by
the Freelite assay were collected for the study and measured with the N-latex
kappaFLC and lambdaFLC assays to assess precision, linearity, method comparison
and dilutional effects. RESULTS: Complex precision showed coefficients of
variation of 4.8-7.2% for the kappaFLC assay and 3.6-6.0% for the lambdaFLC
assay. Linearity assessment showed both assays were linear (kappaFLC, y=1.00x
0.09 and lambdaFLC, y=1.050x-1.252). Qualitative method comparison showed 87.9%
(116/132) agreement and Cohen's kappa of 80.4% between the kappaFLC assays and
72.6% (98/135) agreement and Cohen's kappa of 55.4% for the lambdaFLC assays.
Quantitative method comparison for kappaFLC<150mg/L was y=0.92x+2.21, R=0.661 and
for lambdaFLC<150mg/L was y=7.90x-137.96, R=0.526. Dilutional effects including
antigen excess and non-linearity were also examined. CONCLUSIONS: The N-latex
assay showed good precision and linearity with reasonable agreement to the
Freelite assay. However, the assays should not be used interchangeably to monitor
patients.
PMID- 28512014
TI - Expressional divergence of insect GOX genes: From specialist to generalist
glucose oxidase.
AB - Insect herbivores often secrete glucose oxidase (GOX) onto plants to counteract
plant defenses and potential pathogens. Whether generalist herbivores always have
significantly higher GOX activities than their specialist counterparts at any
comparable stage or conditions and how this is realized remain unknown. To
address these two general questions, we subjected larvae of a pair of sister
species differed mainly in host range, the generalist Helicoverpa armigera and
its specialist counterpart Helicoverpa assulta, to the same sets of stage,
protein to digestible carbohydrate (P:C) ratio, allelochemical or host plant
treatments for simultaneous analyses of GOX transcripts and activities in their
labial glands. GOX activity and transcripts are upregulated concurrently with
food ingestion and body growth, downregulated with stopping ingestion and
wandering for pupation in both species. The three tested host plants upregulated
GOX transcripts, and to a lesser extent, GOX activity in both species. There were
significant differences in both GOX transcripts and activity elicited by
allelochemicals, but only in GOX transcripts by P:C ratios in both species. GOX
activities were higher in H. armigera than H. assulta in all the comparable
treatments, but GOX transcripts were significantly higher either in generalists
or in specialists, depending on the developmental stages, host plants, P:C ratio
and allelochemicals they encounter. These data indicate that the greater GOX
activity in generalist herbivores is not achieved by greater transcription rate,
but by greater transcript stability, greater translation rate, better enzyme
stability and/or their combination.
PMID- 28512015
TI - The association between miR-34 dysregulation and distant metastases formation in
lung adenocarcinoma.
AB - Lung cancer has the highest mortality rate amongst human cancers and the majority
of deaths can be attributed to metastatic spread. The miR-34 family includes
three tumor suppressive miRs: miR-34a, miR-34b and miR-34c. miR-34 downregulation
is a frequent observation in human malignancies and is often attributed to
hypermethylation of the miR-34a and miR-34b/c promoters. Here, the potential
association between aberrant miR-34 expression and promoter methylation and
distant metastases formation in lung adenocarcinoma (LAC) is investigated. The
expression levels of miR-34a, miR-34b and miR-34c, as well as the methylation
status of the miR-34a and miR-34b/c promoters were determined in a LAC patient
cohort comprising 26 non-metastasizing and 26 metastasizing primary LACs, as well
as 24 paired distant metastases and 25 tumor-adjacent normal lung samples using
RT-qPCR and Methylation-Sensitive High Resolution Melting (MS-HRM) analysis. No
difference in expression was observed for miR-34a when comparing metastasizing
and non-metastasizing LACs (p=0.793). For both miR-34b and miR-34c, a
significantly lower expression level was determined in metastasizing LACs
compared to non-metastasizing LACs (p=0.0005 and p=0.002) with similarly
decreased expression levels observed in the paired distant metastases.
Hypermethylation was detected in 35/51 LACs compared to 0/25 tumor-adjacent
normal lungs for the miR-34a promoter (p<0.0001). Similarly, 18/51 LACs compared
to 1/25 tumor-adjacent normal lungs showed hypermethylation of the miR-34b/c
promoter (p=0.003). No difference in methylation was observed between
metastasizing and non-metastasizing LACs for neither the miR-34a (p=0.832) nor
the miR-34b/c (p=0.900) promoter. In conclusion, miR-34a and miR-34b/c promoter
hypermethylation is a frequent event in LAC occurring in 68.7% and 35.3% of
tested cases (n=51), respectively. Low miR-34b and miR-34c expression was
associated with distant metastases formation in LAC. These changes can be
targeted as novel biomarkers in LAC.
PMID- 28512016
TI - Mechanism of action of AMP-jsa9, a LI-F-type antimicrobial peptide produced by
Paenibacillus polymyxa JSa-9, against Fusarium moniliforme.
AB - LI-F type peptides (AMP-jsa9) are a group of cyclic lipodepsipeptides that
exhibit broad antimicrobial spectrum against Gram-positive bacteria and
filamentous fungi. We sought to assess the toxicity of AMP-jsa9 and the mechanism
of AMP-jsa9 action against Fusarium moniliforme. AMP-jsa9 exhibited weak
hemolytic activity and weak cytotoxicity at antimicrobial concentrations
(32MUg/ml). Confocal laser microscopy, SEM, and TEM indicated that AMP-jsa9
primarily targets the cell wall, plasma membrane, and cytoskeleton, increases
membranepermeability, and enhances cytoplasm leakage (e.g., K+, protein).
Quantitative proteomic analysis using isobaric tags for relative and absolute
quantitation (iTRAQ) detected a total of 162 differentially expressed proteins
(59 up-regulated and 103 down-regulated) following treatment of F. moniliforme
with AMP-jsa9. AMP-jsa9 treatment also led to reductions in chitin, ergosterol,
NADH, NADPH, and ATP levels. Moreover, fumonisin B1 expression and biosynthesis
was suppressed in AMP-jsa9-treated F. moniliforme. Our results provide a
theoretical basis for the application of AMP-jsa9 as a natural and effective
antifungal agent in the agricultural, food, and animal feed industries.
PMID- 28512017
TI - A case of autoimmune severe acquired von Willebrand syndrome (type 3-like).
AB - Von Willebrand disease (VWD) is the most common congenital bleeding disorder and
is due to quantitative or qualitative defects of von Willebrand factor (VWF).
Acquired defects of VWF, termed acquired von Willebrand syndrome (AVWS), are due
to a host of different mechanisms. Autoantibody-mediated AVWS may be associated
with lymphoproliferative or immunological disorders, such as systemic lupus
erythematosus (SLE). A large majority of AVWS cases are type 1 or type 2A-like
and patients tend to have a mild to moderate bleeding tendency. We report a case
of severe autoimmune AVWS in a woman with SLE who presented with clinical and
laboratory features of type 3 VWD (undetectable VWF antigen, ristocetin cofactor
activity, and VWF multimers). A mixing study demonstrated an inhibitor to VWF
(6BU/mL). Her bleeds were managed with antifibrinolytics, recombinant activated
factor VII, and activated prothrombin complex concentrate. She was initially
treated with steroids and intravenous immunoglobulin therapy. However, her
bleeding symptoms continued until she was treated with rituximab, and her VWF
parameters normalized. She relapsed two years later due to non-compliance with
her immunosuppressive medications and expired another two years later secondary
to complications of sepsis and uremic pericarditis. This case emphasizes the
importance of aggressive initial therapy of SLE to reduce secondary
complications, frequent patient monitoring, and continued treatment of the
underlying autoimmune disorder in patients with AVWS.
PMID- 28512018
TI - Nanoencapsulation of a glucocorticoid improves barrier function and anti
inflammatory effect on monolayers of pulmonary epithelial cell lines.
AB - The anti-inflammatory effect of polymeric deflazacort nanocapsules (NC-DFZ) was
investigated, and possible improvement of epithelial barrier function using
filter grown monolayers of Calu-3 cells was assessed. NC prepared from
poly(epsilon-caprolactone) (PCL) had a mean size around 200nm, slightly negative
zeta potential (~-8mV), and low polydispersity index (<0.10). Encapsulation of
DFZ had an efficiency of 85%. No cytotoxic effects were observed at particle
concentration of 9.85*1011NC/ml, which was therefore chosen to evaluate the
effect of NC-DFZ at 1% (w/v) of PCL and 0.5% (w/v) of DFZ on the epithelial
barrier function of Calu-3 monolayers. Nanoencapsulated drug at 0.5% (w/v)
increased transepithelial electrical resistance and decreased permeability of the
paracellular marker sodium fluorescein, while non-encapsulated DFZ failed to
improve these parameters. Moreover, NC-DFZ reduced the lipopolysaccharide (LPS)
mediated secretion of the inflammatory marker IL-8. In vitro dissolution testing
revealed controlled release of DFZ from nanocapsules, which may explain the
improved effect of DFZ on the cells. These data suggest that nanoencapsulation of
pulmonary delivered corticosteroids could be advantageous for the treatment of
inflammatory conditions, such as asthma and chronic obstructive pulmonary
diseases.
PMID- 28512019
TI - Novel inulin-based mucoadhesive micelles loaded with corticosteroids as potential
transcorneal permeation enhancers.
AB - In this work a new copolymer of inulin (INU) derivatized with ethylendiamine
(EDA) and retinoic acid (RA), named INU-EDA-RA, was synthetized, characterized
and employed to produce micelles as carriers for topical administration of
corticosteroids for the potential treatment of diseases of posterior eye segment.
Spectroscopic analysis confirmed a molar derivatization degree of 11.30 and 4.30%
in EDA and RA, respectively. INU-EDA-RA micelles are capable of strong
mucoadhesive interactions which result time-independent and stable over time but
concentration depending. Moreover micelles are able to encapsulate efficiently
from 3 to 13% (w/w) of lipophilic drugs, as dexamethasone, triamcinolone and
triamcinolone acetonide. Drug loaded micelles are stable for three months when
stored as freeze-dried powders and able to release high amount of drug when
compared to drug dissolution profiles from suspensions. Moreover, drug loaded
micelles are compatible with different ocular cell lines that are also able to
internalize fluorescent micelles. Finally, drug loaded micelles enhance drug
fluxes and permeability coefficients across corneal epithelial cells, thus
reducing drug loss due to retention inside the cells.
PMID- 28512020
TI - Molecular epidemiology of porcine reproductive and respiratory syndrome virus in
Central China since 2014: The prevalence of NADC30-like PRRSVs.
AB - Porcine reproductive and respiratory syndrome (PRRS), characterized by
respiratory disorders in piglets and reproductive failure in sows, is still the
great threat of swine industry. Recently, Emergence of the novel NADC30-like PRRS
viruses (PRRSVs) has caused widespread outbreaks of PRRS. To investigate the
epidemic characteristics of PRRSVs in Central China since 2014, 6372 clinical
serum samples were tested by ELISA, 250 tissue samples were tested by RT-PCR, and
among these, 30 ORF5 and 17 Nsp2 genes sequences were analyzed. Phylogenetic tree
based on ORF5 revealed that, 17 isolates were clustered into subgroup 1,
represented by the NADC30. And for the Nsp2, The strains which had a
discontinuous 131-amino-acid deletion in Nsp2, called NADC30-like strains, were
clustered into subgroup 2. Our data suggested that the NADC30-like PRRSV strains
spread quickly and are now circulating and prevalent in Central China as well as
the classical HP-PRRSV strains. In addition, amino acid variation analysis of GP5
revealed that the amino acid sequences of NADC30-like PRRSV strains underwent
rapid evolution and contained extensive amino acid substitutions in important
motifs, such as potential neutralization epitope and the N-glycosylation sites.
In summary, our data would provide a large amount of detailed information on
molecular variation and genetic diversity of PRRSV in central China.
PMID- 28512021
TI - Statin Use After Diagnosis of Colon Cancer and Patient Survival.
AB - BACKGROUND & AIMS: Statin use has been associated with a reduced incidence of
colorectal cancer and might also affect survival of patients diagnosed with colon
cancer. Statins are believed to inhibit Ras signaling and may also activate the
bone morphogenetic protein (BMP) signaling pathway in colorectal cancer cells. We
investigated the effects of statins on overall survival of patients with a
diagnosis of colon cancer, and whether their effects were associated with changes
in KRAS or the BMP signaling pathways. METHODS: Data were derived from the PHARMO
database network (Netherlands) and linked to patients diagnosed with colon cancer
from 2002 through 2007, listed in the Eindhoven Cancer Registry. We obtained
information on causes of death from statistics Netherlands. We constructed a
tissue microarray of 999 colon cancer specimens from patients who underwent
surgical resection from 2002 through 2008. Survival was analyzed with statin user
status after diagnosis as a time-dependent covariate. Multivariable Poisson
regression survival models and Cox analyses were used to study the effect of
statins on survival. Tumor tissues were analyzed by immunohistochemistry for
levels of SMAD4, BMPR1A, BMPR1B, and BMPR2 proteins. Tumor tissues were
considered to have intact BMP signaling if they contained SMAD4 plus BMPR1A,
BMPR1B, or BMPR2. DNA was isolated from tumor tissues and analyzed by
quantitative polymerase chain reaction to detect mutations in KRAS. The primary
outcome measures were overall mortality and cancer-specific mortality. RESULTS:
In this cohort, 21.0% of the patients (210/999) were defined as statin users
after diagnosis of colon cancer. Statin use after diagnosis was significantly
associated with reduced risk of death from any cause (adjusted relative risk
[RR], 0.67; 95% confidence interval [CI], 0.51-0.87; P = .003) and death from
cancer (adjusted RR, 0.66; 95% CI, 0.49-0.89; P = .007). Statin use after
diagnosis was associated with reduced risk of death from any cause or from cancer
for patients whose tumors had intact BMP signaling (adjusted RR, 0.39; 95% CI,
0.22-0.68; P = .001), but not for patients whose tumors did not have BMP
signaling (adjusted RR, 0.81; 95% CI, 0.55-1.21; P = .106; P < .0001 for the
interaction). Statin use after diagnosis was not associated with reduced risk of
death from any cause or from cancer for patients whose tumors did not contain
KRAS mutations (adjusted RR, 0.81; 95% CI, 0.56-1.18; P = .273) or whose tumors
did have KRAS mutations (adjusted RR, 0.59; 95% CI 0.35-1.03; P = .062; P = .90
for the interaction). CONCLUSIONS: In an analysis of 999 patients with a
diagnosis of colon cancer, we associated statin with reduced risk of death from
any cause or from cancer. The benefit of statin use is greater for patients whose
tumors have intact BMP signaling, independent of KRAS mutation status. Randomized
controlled trials are required to confirm these results.
PMID- 28512022
TI - Synthesis, antimycobacterial activity and docking study of 2-aroyl
[1]benzopyrano[4,3-c]pyrazol-4(1H)-one derivatives and related hydrazide
hydrazones.
AB - A new convenient method for preparation of 2-aroyl-[1]benzopyrano[4,3-c]pyrazol
4(1H)-one derivatives 5b-g and coumarin containing hydrazide-hydrazone analogues
4a-e was presented. The antimycobacterial activity against reference strain
Mycobacterium tuberculosis H37Rv and cytotoxicity against the human embryonic
kidney cell line HEK-293 were tested in vitro. All compounds demonstrated
significant minimum inhibitory concentrations (MIC) ranging 0.28-1.69MUM, which
were comparable to those of isoniazid. The cytotoxicity (IC50>200uM) to the
"normal cell" model HEK-293T exhibited by 2-aroyl-[1]benzopyrano[4,3-c]pyrazol
4(1H)-one derivatives 5b-e, was noticeably milder compared to that of their
hydrazone analogues 4a-e (IC50 33-403uM). Molecular docking studies on compounds
4a-e and 5b-g were also carried out to investigate their binding to the 2-trans
enoyl-ACP reductase (InhA) enzyme involved in M. tuberculosis cell wall
biogenesis. The binding model suggested one or more hydrogen bonding and/or arene
H or arene-arene interactions between hydrazones or pyrazole-fused coumarin
derivatives and InhA enzyme for all synthesized compounds.
PMID- 28512023
TI - Synthesis and biological evaluation of novel 5-aryl-4-(5-nitrofuran-2-yl)
pyrimidines as potential anti-bacterial agents.
AB - A facile two-step synthetic approach to fluorinated and non-fluorinated 5-aryl-4
(5-nitrofuran-2-yl)-pyrimidines from readily available 5-bromo-4-(furan-2
yl)pyrimidine has been developed. All synthesized compounds were screened in
vitro for their antibacterial activities against twelve various bacterial
strains. It is demonstrated that some of these compounds exhibited significant
antibacterial activities against strains Neisseria gonorrhoeae and Staphylococcus
aureus, comparable and even higher with that commercial drug Spectinomycin.
PMID- 28512025
TI - Synthesis of methanesulphonamido-benzimidazole derivatives as gastro-sparing
antiinflammatory agents with antioxidant effect.
AB - A series of 5-methanesulphonamido benzimidazole derivatives were designed by
combining the structural features of clinically useful anti-inflammatory drugs
(nimesulide and rofecoxib) and antiulcer drugs (lansoprazole, omeprazole, etc.)
based on physicochemical and 3D similarity studies. The compounds were evaluated
for their anti-inflammatory activity in carrageenan induced rat paw edema model
taking rofecoxib and indomethacin as standard drugs. In vitro antioxidant
activity of the compounds was assessed by potassium ferricyanide reducing power
(PFRAP) assay. The compounds 9, 10 and 11 showed anti-inflammatory activity
comparable to the standard group and were also non-ulcerogenic at the test doses.
Compounds 6-11 exhibited good antioxidant effect in the concentration range (1.0
50.0umol/ml. Preliminary theoretical ADME profiling of the compounds based on
computation of selected physicochemical properties showed an excellent compliance
with Lipinski's rule.
PMID- 28512024
TI - Repurposing of Proton Pump Inhibitors as first identified small molecule
inhibitors of endo-beta-N-acetylglucosaminidase (ENGase) for the treatment of
NGLY1 deficiency, a rare genetic disease.
AB - N-Glycanase deficiency, or NGLY1 deficiency, is an extremely rare human genetic
disease. N-Glycanase, encoded by the gene NGLY1, is an important enzyme involved
in protein deglycosylation of misfolded proteins. Deglycosylation of misfolded
proteins precedes the endoplasmic reticulum (ER)-associated degradation (ERAD)
process. NGLY1 patients produce little or no N-glycanase (Ngly1), and the
symptoms include global developmental delay, frequent seizures, complex
hyperkinetic movement disorder, difficulty in swallowing/aspiration, liver
dysfunction, and a lack of tears. Unfortunately, there has not been any
therapeutic option available for this rare disease so far. Recently, a proposed
molecular mechanism for NGLY1 deficiency suggested that endo-beta-N
acetylglucosaminidase (ENGase) inhibitors may be promising therapeutics for NGLY1
patients. Herein, we performed structure-based virtual screening utilizing FDA
approved drug database on this ENGase target to enable repurposing of existing
drugs. Several Proton Pump Inhibitors (PPIs), a series of substituted 1H-benzo
[d] imidazole, and 1H-imidazo [4,5-b] pyridines, among other scaffolds, have been
identified as potent ENGase inhibitors. An electrophoretic mobility shift assay
was employed to assess the inhibition of ENGase activity by these PPIs. Our
efforts led to the discovery of Rabeprazole Sodium as the most promising hit with
an IC50 of 4.47+/-0.44MUM. This is the first report that describes the discovery
of small molecule ENGase inhibitors, which can potentially be used for the
treatment of human NGLY1 deficiency.
PMID- 28512026
TI - One-pot synthesis and biological evaluation of N-(aminosulfonyl)-4
podophyllotoxin carbamates as potential anticancer agents.
AB - A series of N-(aminosulfonyl)-4-podophyllotoxin carbamates were synthesized via
the Burgess-type intermediate, and their antiproliferative activities were
evaluated. Most of them possessed more potent cytotoxic effects against four
human tumor cell lines (HeLa, A-549, HCT-8 and HepG2) and less toxic to normal
human fetal lung fibroblast WI-38 cells than etoposide. In particular, N
(morpholinosulfonyl)-4-podophyllotoxin carbamate (9) exhibited the most potent
activity towards these four tumor cells with IC50 values in the range of 0.5
16.5MUM. Furthermore, immunofluorescence analysis revealed that 9 induced cell
apoptosis by up-regulating the expression of p53 and ROS. Meanwhile, 9
effectively inhibited tubulin polymerization and microtubule assembly at cellular
levels in HeLa cells. In addition, 9 could induce cell cycle arrest in the G2/M
phase in HeLa cells by up-regulating levels of cyclinB1 and cdc2 and decreasing
the expression of p-cdc2. These results indicated that 9 had potential for
further development as anticancer agents.
PMID- 28512027
TI - Insights into the myosin II inhibitory potency of A-ring-modified (S)
blebbistatin analogs.
AB - Myosin II is an interesting target for therapeutic intervention, as it is
involved in a large number of motility-based diseases. (S)-Blebbistatin is a
known micromolar inhibitor of this protein. A new series of (S)-blebbistatin
derivatives with a modified A-ring was synthesized and the myosin II inhibitory
properties were evaluated in vitro. In this way, we gained insight into the
influence of structural modifications in this part of the scaffold on myosin II
inhibitory potency. Our results indicate there are few possibilities for potency
enhancement via ring A modification of the blebbistatin scaffold.
PMID- 28512028
TI - Evaluation of synthesized coumarin derivatives on aromatase inhibitory activity.
AB - In women across the world, the most common type of cancer is breast cancer. Among
medical treatments, endocrine therapy based on aromatase inhibitors (AI) is
expected to be effective against not only post-menopausal but also pre-menopausal
breast cancer. In this study, we examined the structure-activity relationship
between the aromatase inhibitory effects of 7-diethylaminocoumarin derivatives
with a substituent at position 3 and coumarin derivatives with a substituent at
position 7. Consequently, we found that 7-(pyridin-3-yl)coumarin (IC50 values
30.3nM) and 7,7'-diethylamino-3,3'-biscoumarin (28.7nM) are the most potent
inhibitors of aromatase. These inhibitors were found to be comparable to the
existing CYP19 inhibitor exemestane (42.5nM).
PMID- 28512029
TI - Calixarene-mediated liquid membrane transport of choline conjugates 3: The effect
of handle variation on neurotransmitter transport.
AB - Upper rim phosphonic acid functionalized calix[4]arene affects selective
transport of multiple molecular payloads through a liquid membrane. The secret is
in the attachment of a receptor-complementary handle to the payload. We find that
the trimethylammonium ethylene group present in choline is one of several general
handles for the transport of drug and drug-like species. Herein we compare the
effect of handle variation against the transport of serotonin and dopamine. We
find that several ionizable amine termini handles are sufficient for transport
and identify two ideal candidates. Their performance is significantly enhanced in
HEPES buffered solutions. This inquiry completes a series of 3 studies aimed at
optimization of this strategy. In completion a new approach towards synthetic
receptor mediated selective small molecule transport has emerged; future work in
vesicular and cellular systems will follow.
PMID- 28512030
TI - Discovery of potent and orally active 1,4-disubstituted indazoles as novel
allosteric glucokinase activators.
AB - Guided by co-crystal structural information obtained from a different series we
were exploring, a scaffold morphing and SBDD approach led to the discovery of the
1,4-disubstituted indazole series as a novel class of GKAs that potently activate
GK in enzyme and cell assays. anti-diabetic OGTT efficacy was demonstrated with
29 in a rodent models of type 2 diabetes.
PMID- 28512031
TI - From a novel HTS hit to potent, selective, and orally bioavailable KDM5
inhibitors.
AB - A high-throughput screening (HTS) of the Genentech/Roche library identified a
novel, uncharged scaffold as a KDM5A inhibitor. Lacking insight into the binding
mode, initial attempts to improve inhibitor potency failed to improve potency,
and synthesis of analogs was further hampered by the presence of a C-C bond
between the pyrrolidine and pyridine. Replacing this with a C-N bond
significantly simplified synthesis, yielding pyrazole analog 35, of which we
obtained a co-crystal structure with KDM5A. Using structure-based design
approach, we identified 50 with improved biochemical, cell potency and reduced MW
and lower lipophilicity (LogD) compared with the original hit. Furthermore, 50
showed lower clearance than 9 in mice. In combination with its remarkably low
plasma protein binding (PPB) in mice (40%), oral dosing of 50 at 5mg/kg resulted
in unbound Cmax ~2-fold of its cell potency (PC9 H3K4Me3 0.96MUM), meeting our
criteria for an in vivo tool compound from a new scaffold.
PMID- 28512032
TI - Cytotoxic triterpene diglycosides from the sea cucumber Stichopus horrens.
AB - Using various chromatographic separation techniques, eight triterpene
diglycosides (1-8), including four new compounds namely stichorrenosides A-D (1
4), were isolated from a methanol extract of the Vietnamese sea cucumber S.
horrens. Their structures were elucidated based on spectroscopic analyses,
including HR ESI MS, 1D and 2D NMR. Their in vitro cytotoxic activity against
five human cancer cell lines, Hep-G2 (hepatoma cancer), KB (epidermoid
carcinoma), LNCaP (prostate cancer), MCF7 (breast cancer), and SK-Mel2
(melanoma), was evaluated using SRB methods. Stichorrenoside D (4), stichoposide
A (5), and 3beta-O-[beta-d-xylopyranosyl-(1->2)-beta-d-xylopyranosyl]-23S
acetoxyholost-7-ene (7) showed strong cytotoxicity on all five tested cancer cell
lines, whereas significant effect was observed for stichorrenoside C (3) and
stichoposide B (6).
PMID- 28512033
TI - Bifidobacterium CECT 7765 modulates early stress-induced immune, neuroendocrine
and behavioral alterations in mice.
AB - Emerging evidence suggests that there is a window of opportunity within the early
developmental period, when microbiota-based interventions could play a major role
in modulating the gut-brain axis and, thereby, in preventing mood disorders. This
study aims at evaluating the effects and mode of action of Bifidobacterium
pseudocatenulatum CECT 7765 in a murine model of chronic stress induced by
maternal separation (MS). C57Bl/6J male breast-fed pups were divided into four
groups, which were subjected or not to MS and supplemented with placebo or B.
pseudocatenulatum CECT7765 until postnatal period (P) 21 and followed-up until
P41. Behavioral tests were performed and neuroendocrine parameters were analyzed
including corticosterone, cytokine/chemokine concentrations and
neurotransmitters. Microbiota was also analyzed in stools by 16S rRNA gene
sequencing. B. pseudocatenulatum CECT 7765 administration attenuated some aspects
of the excessive MS-induced stress response of the hypothalamic-pituitary-adrenal
(HPA) axis, particularly corticosterone production at baseline and in response to
subsequent acute stress in adulthood. B. pseudocatenulatum CECT 7765 also down
regulated MS-induced intestinal inflammation (reducing interferon gamma [IFN
gamma]) and intestinal hypercatecholaminergic activity (reducing dopamine [DA]
and adrenaline [A] concentrations) at P21. These effects have a long-term impact
on the central nervous system (CNS) of adult mice since MS mice fed B.
pseudocatenulatum CECT 7765 showed lower anxiety levels than placebo-fed MS mice,
as well as normal neurotransmitter levels in the hypothalamus. The anti
inflammatory effect of B. pseudocatenulatum CECT 7765 seemed to be related to an
improvement in glucocorticoid sensitivity in mesenteric lymph node
immunocompetent cells at P21. The administration of B. pseudocatenulatum CECT
7765 to MS animals also reversed intestinal dysbiosis affecting the proportions
of ten Operational Taxonomic Units (OTUs) at P21, which could partly explain the
restoration of immune, neuroendocrine and behavioral alterations caused by stress
in early and later life. In summary, we show that B. pseudocatenulatum CECT 7765
is able to beneficially modulate the consequences of chronic stress on the HPA
response produced by MS during infancy with long-lasting effects in adulthood,
via modulation of the intestinal neurotransmitter and cytokine network with short
and long-term consequences in brain biochemistry and behavior.
PMID- 28512034
TI - Diagnostic yield of capsule endoscopy versus magnetic resonance enterography and
small bowel contrast ultrasound in the evaluation of small bowel Crohn's disease:
Systematic review and meta-analysis.
AB - BACKGROUND AND AIMS: Capsule endoscopy (CE), magnetic resonance enterography
(MRE) and small bowel (SB) intestinal contrast ultrasound (SICUS) are the
modalities of choice for SB evaluation. This study aimed to compare the
diagnostic yield (DY) of CE to MRE and SICUS in detection and monitoring of SB CD
through meta-analysis of the available literature. METHODS: We performed a
systematic literature search for trials comparing the accuracy of CE, MRE and
SICUS for detection of active SB inflammation in patients with suspected and/or
established CD. Only prospective studies comparing CE with another additional
diagnostic modality were included in the final analysis. Pooled odds ratios (ORs)
for the DY of the three modalities were calculated. RESULTS: A total of 112
studies were retrieved; following selection, 13 studies were eligible for
analysis. The DY of CE for detection of active SB CD was similar to that of MRE
(10 studies, 400 patients, OR 1.17; 95% CI 0.83-1.67) and SICUS (5 studies, 142
patients, OR 0.88; 95% CI 0.51-1.53). The outcomes were similar for the subgroups
of suspected versus established CD and adult versus pediatric patients. CE was
superior to MRE for proximal SB CD (7 studies, 251 patients, OR 2.79; 95% CI 1.2
6.48); the difference vs SICUS was not significant. CONCLUSION: CE, MRE and SICUS
have similar DY for detection of SB CD in both suspected and established CD. CE
is superior to MRE for detection of proximal SB disease, however the risk of
capsule retention should be considered.
PMID- 28512035
TI - The predatory behavior of the Neotropical social wasp Polybia rejecta.
AB - We experimentally studied the predatory behavior of Polybia rejecta (Vespidae,
Polistinae, Epiponini) towards 2-88 mm-long insects attracted to a UV light trap.
Foragers, which began to hunt at 6:30, selected 4-14 mm-long prey insects. Prey
detection by sight by hovering wasps was confirmed using decoys. After the wasps
landed and walked along a sinuous path, prey were detected by contact or from a
distance (1-3cm). This was followed by seizure, stinging (contrarily to most
other known cases), prey manipulation and retrieval. Prey that flew off might be
caught in flight. The prey load, representing 30.7% of a forager's weight, was
optimized by capturing up to six small prey or two medium-sized prey successively
(both of which might be consumed in situ). The foragers cut off the wings of
larger prey or cut them into two pieces and returned to gather the second piece.
The handling time increased exponentially with the weight of the prey. Partial
loading (i.e., retrieving a load much inferior to the maximum possible) was
likely related to social facilitation, a form of nest-based recruitment that was
demonstrated through the experimental elimination of local enhancement by
removing foragers (both mechanisms favor the exploitation of favorable patches).
PMID- 28512036
TI - Vocal responses of austral forest frogs to amplitude and degradation patterns of
advertisement calls.
AB - Degradation phenomena affecting animal acoustic signals may provide cues to
assess the distance of emitters. Recognition of degraded signals has been
extensively demonstrated in birds, and recently studies have also reported
detection of degraded patterns in anurans that call at or above ground level. In
the current study we explore the vocal responses of the syntopic burrowing male
frogs Eupsophus emiliopugini and E. calcaratus from the South American temperate
forest to synthetic conspecific calls differing in amplitude and emulating
degraded and non-degraded signal patterns. The results show a strong dependence
of vocal responses on signal amplitude, and a general lack of differential
responses to signals with different pulse amplitude modulation depths in E.
emiliopugini and no effect of relative amplitude of harmonics in E. calcaratus.
Such limited discrimination of signal degradation patterns from non-degraded
signals is likely related to the burrowing habits of these species. Shelters
amplify outgoing and incoming conspecific vocalizations, but do not counteract
signal degradation to an extent comparable to calling strategies used by other
frogs. The limited detection abilities and resultant response permissiveness to
degraded calls in these syntopic burrowing species would be advantageous for
animals communicating in circumstances in which signal alteration prevails.
PMID- 28512037
TI - Understanding behavior under nonverbal transitive-inference procedures: Stimulus
control-topography analyses.
AB - Following training with verbal stimulus relations involving A is greater than B
and B is greater than C, verbally-competent individuals reliably select A>C when
asked "which is greater, A or C?" (i.e., verbal transitive inference). This
result is easy to interpret. Nonhuman animals and humans with and without
intellectual disabilities have been exposed to nonverbal transitive-inference
procedures involving trained arbitrary stimulus relations. Following the training
of A+B-, B+C-, C+D-, and D+E-, B reliably is selected over D (i.e., nonverbal
transitive inference). Such findings are more challenging to interpret. The
present research explored accounts of nonverbal transitive inference based in
transitive inference per se, reinforcement, such as value-transfer theory, and
operant stimulus control. In Experiment 1, college students selected B>G
following the training of A+B-, B+C-, C+D-///E+F-, F+G-, and G+H-
(where///signifies the omission of D+E-). In Experiment 2, college students
selected B>G following the training of A+B-, B+C-, C+D-///E+F-, F+G-, and G+X-
(where X refers to 10 stimuli that alternated across trials). In Experiment 3,
college students selected G>B following the training of Y+B-, B+C-, C+D-///E+F-,
F+G-, and G+X- (where Y and X refer to 10 stimuli, respectively, that alternated
across trials). These findings are discussed in the context of operant stimulus
control by offering an approach based in stimulus B typically acquiring only a
select stimulus control topography.
PMID- 28512038
TI - Involvement of the oxytocin system in the nucleus accumbens in the regulation of
juvenile social novelty-seeking behavior.
AB - Exploration of novel environments, stimuli, and conspecifics is highly adaptive
during the juvenile period, as individuals transition from immaturity to
adulthood. We recently showed that juvenile rats prefer to interact with a novel
individual over a familiar cage mate. However, the neural mechanisms underlying
this juvenile social novelty-seeking behavior remain largely unknown. One
potential candidate is the oxytocin (OXT) system, given its involvement in
various motivated social behaviors. Here, we show that administration of the
specific oxytocin receptor antagonist desGly-NH2,d(CH2)5-[Tyr(Me)2,Thr4]OVT
reduces social novelty seeking-behavior in juvenile male rats when injected into
the nucleus accumbens (10ng/0.5MUl/side). The same drug dose was ineffective at
altering social novelty-seeking behavior when administered into the lateral
septum or basolateral amygdala. These results are the first to suggest the
involvement of the OXT system in the nucleus accumbens in the regulation of
juvenile social novelty-seeking behavior.
PMID- 28512039
TI - Fluorescein-Guided Surgery for High-Grade Glioma Resection: An Intraoperative
"Contrast-Enhancer".
AB - BACKGROUND: Fluorescein sodium salt is widely used in medicine as fluorescein
isothiocyanate and commonly named fluorescein (FL). This fluorophore has been
used as a fluorescent tracer for many applications, especially in ophthalmic
surgery. It was initially used in neuro-oncology in 1948 to control tumor
resection margins. After a transient disuse, it has recently had a second spring
with the development of dedicated filters for operating microscopes, although it
is still under evaluation in clinical use. The aim of this study is to contribute
to the investigation according to which FL-guided surgery for high-grade glioma
(HGG) is related to better rates of gross total resection (GTR) and so to a
better outcome. METHODS: We retrospectively analyzed 23 cases of patients with
new diagnosis of HGG, operated on in our unit by intraoperative FL use with a
filter system directly integrated into an operative microscope (group 1).
Fluorescence was compared with histology by biopsies carried out both in the
fluorescent areas and in the periphery of fluorescent areas. Group 1 was matched
with a control group of 25 patients with HGG operated on in our unit during the
last 2 years without FL guidance (group 2). RESULTS: No side effects occurred
related to FL. Histology and intraoperative neuronavigation showed strong
correspondence with fluorescent and nonfluorescent areas. GTR rate was
significantly higher in group 1 (82.6%) than in group 2 (52%). CONCLUSIONS:
Intraoperative fluorescein-guided surgery showed safety and feasibility. Our and
other studies suggest an improvement of GTR rate in HGG than nonuse.
PMID- 28512040
TI - Meningiomas Adjacent to Major Venous Sinuses-Clinical Outcome and Recurrence.
AB - BACKGROUND: Surgical treatment of meningiomas next to venous sinuses is difficult
because of their irregular growth patterns and infiltration into the venous
sinuses, making gross total resection impossible in some patients. We evaluated
the postoperative clinical and neurologic course of this tumor subgroup. METHODS:
This study included 141 consecutive patients with meningioma located within 20 mm
of a major venous sinus. Complete data sets were available for all patients. We
reviewed patient charts and surgical reports for demographics, histology, and
clinical and neurologic performance preoperatively and postoperatively and during
follow-up. Radiographic images were screened for tumor extension, infiltration
into the skull, sinus infiltration (Sindou grade), extent of resection (Simpson
grade), and tumor recurrence. RESULTS: Immediate postoperative neurologic
improvement was found in 53.7% (n = 36) of patients with preoperative neurologic
deficits (n = 67). Follow-up was up to 13.5 years. Medical Research Council
Neurological Performance Scale and Karnofsky performance scale postoperatively
improved in 24.1% and 55.3% of patients, respectively. Local tumor recurrence was
detected in 10.6% (n = 15) of patients. Higher World Health Organization grade (P
= 0.03), tumor size (P = 0.001), and bone invasion (P = 0.002) were predictors of
local tumor recurrence. The median MIB-1 labeling index in patients with tumor
recurrence was twice as high as in patients without recurrence. CONCLUSIONS:
Surgical removal of meningiomas adjacent to venous sinuses reduces neurologic
impairment and enables local tumor control in most patients. Tumor size, bone
infiltration, and higher World Health Organization grade are important predictors
of tumor recurrence.
PMID- 28512041
TI - Characteristics of Blood Pressure Profiles After Endovascular Coiling as
Predictors of Clinical Outcome in Poor-Grade Aneurysmal Subarachnoid Hemorrhage.
AB - OBJECTIVE: Accurate identification of patients who will achieve a favorable
outcome is almost impossible preoperatively or postoperatively in poor-grade
(Hunt and Hess Grade IV and V) aneurysmal subarachnoid hemorrhage (SAH). Whether
characteristics of blood pressure profiles during the first 24 hours after
endovascular coiling could predict prognosis in poor grade patients was explored.
METHODS: Data were obtained retrospectively on all patients undergoing
endovascular treatment with poor-grade SAH from November 2011 to June 2016. Blood
pressure during the initial 24 hours was measured at 2-hour intervals after coil
embolization. Studied features of mean systolic blood pressure (MSBP) and
systolic blood pressure variability (SBPV) as well as demographics, medical
history, clinical characteristics, and neurologic outcomes were documented. SBPV
was determined as standard deviation and successive variation of systolic blood
pressure. Logistic regression analysis was used to identify predictors of
favorable outcome assessed on modified Rankin Scale score of 0 to 2. RESULTS: The
patients with favorable and unfavorable outcome were comparable with respect to
systolic blood pressure on admission and MSBP after coiling. However, MSBP
between 120 and 140 mm Hg was one of independent predictors of good outcomes at
discharge (odds ratio 7.1; P = 0.002). SBPV-successive variation after
embolization was associated with functional recovery (odds ratio 0.87; P = 0.011)
in multivariate logistic analysis and mortality by Cox proportional hazard
regression (hazard ratio, 1.10; P = 0.001) at 6-month follow-up. CONCLUSIONS:
Characteristics of blood pressure profiles after coiling appeared to be simple
and convenient indexes for the prognosis of patients with poor-grade SAH.
PMID- 28512042
TI - The Corona Dentis: Description of an Anatomic Variant with Technical Implications
for Anterior Odontoid Screw Placement.
AB - BACKGROUND: Type 2 odontoid fractures are the most common cervical fractures
among the elderly. Neurologic deficit is usually caused by myelopathy as a result
of posterior dens migration. Direct anterior screw placement provides
stabilization and can preserve C1-C2 movement. The presence of a bony excrescence
on the anterior superior tip of the dens may lead to placement of a screw of
incorrect length. METHODS: Twenty C2 dry specimens were examined for the presence
of a corona dentis, which is a bony excrescence in the coronal plane near the
apex of the dens. When identified, measurements of the corona dentis were
performed using calipers and a ruler. In addition, anteroposterior (AP) and
lateral fluoroscopy was performed on all specimens found to have a corona dentis.
RESULTS: A corona dentis was found on 20% of our C2 specimens and had an average
width of 9 mm and an average height of 4.5 mm. The average width of the dens did
not vary as the normal tip of the dens transitioned into the coronae. In no
specimen did the corona dentis seem to be composed of trabecular bone and it was
seen as a superior projection of cortical bone on fluoroscopy. On fluoroscopy,
the corona dentis could be identified on a true AP projection. In angulated AP
views, fluoroscopic images overestimated the length of the corona dentis.
CONCLUSIONS: We describe a new entity termed the corona dentis because of its
crownlike feature. It is a superior cortical bone protrusion and should be noted
as a variant of the dens during anterior odontoid screw placement. Its propensity
to increase the height of the dens markedly can lead to higher rates of
neurologic deficits during type 2 odontoid fractures if not appreciated. A true
AP view is critical for correct screw size placement.
PMID- 28512043
TI - Endoscopic Assisted Supraorbital Keyhole Approach or Endoscopic Endonasal
Approach in Cases of Tuberculum Sellae Meningioma: Which Surgical Route Should Be
Favored?
AB - OBJECTIVE: Keyhole approaches are under investigation for skull base tumor
surgery. They are expected to have a low complication rate with the same
successful resection rate compared with endoscopic endonasal procedures. In this
study, we compare our current series of tuberculum sellae meningiomas resected
via an endoscopic endonasal or microsurgical supraorbital keyhole approach.
METHODS: Between 2011 and 2016, 16 patients were treated using the supraorbital
keyhole procedure and 6 patients received an endoscopic endonasal procedure. Both
surgical techniques were analyzed and compared concerning complications, surgical
radicality, endocrinologic, and ophthalmologic outcome and recurrences in
patients' follow-up. RESULTS: The 2 different approaches yielded similar rates of
gross total resection (endonasal 83% [5 of 6] vs. supraorbital 87% [14 of 16]),
near total resection (17% [1 of 6] vs. 13% [2 of 16]), and visual recovery
(endonasal 66% [2 of 3] vs. supraorbital 60% [3 of 5]). An extension lateral to
the internal carotid artery was noted in 81% (13 of 16) of the supraorbital cases
and in none of the endonasal cases. Tumor volume was 14.9 cm3 (+/-8.2 cm3) for
supraorbital tumors versus 2.1 cm3 (+/-0.8 cm3) for the endonasal approach.
CONCLUSIONS: Both approaches provide minimally invasive surgical routes accessing
meningiomas of the sellar region. The ideal approach should be tailored to the
individual patient considering the tumor anatomy, lateral extension, and the
experience of the surgeon with both surgical approaches. We suggest using the
supraorbital approach for larger meningiomas of sellar region with far lateral
extension or broad vascular encasement.
PMID- 28512044
TI - Spinal Solitary Fibrous Tumor/Hemangiopericytoma: A Clinicopathologic and
Radiologic Analysis of Eleven Cases.
AB - OBJECTIVE: To retrospectively review the clinicopathologic features and computed
tomography (CT) and magnetic resonance imaging (MRI) findings of spinal solitary
fibrous tumor (SFT)/hemangiopericytoma (HPC) tumors. METHODS: Eleven patients
with surgically and pathologically confirmed spinal SFT/HPC were enrolled. Their
clinicopathologic data and imaging findings were retrospectively reviewed.
RESULTS: There were 8 male and 3 female patients with a median age of 42 years
(range, 26-65 years). Of the 11 patients, 5 were classified as grade I, 4 were
grade II, and the remaining 2 were grade III. CT or MRI showed a well-defined (n
= 8) or ill-defined (n = 3), oval (n = 4), irregular (n = 3), dumbbell-shaped (n
= 3), and striped (n = 1) mass with heterogeneous (n = 10) or homogeneous (n = 1)
density. The lesions appeared isointense (n = 4) or hypointense (n = 5) on T1
weighted MRI and mildly hyperintense (n = 3) or hyperintense (n = 6) on T2
weighted MRI. Bone destruction was observed in 7 cases, including osteolytic (n =
6) and osteoblastic (n = 1) patterns. Calcification was observed in only 1 case.
On enhanced CT/MRI, marked (n = 9), mild (n = 1) heterogeneous, and marked
homogeneous (n = 1) enhancement were observed in this study. CONCLUSIONS: Spinal
SFT/HPC commonly appears as a well-defined solitary mass characterized by a black
and white appearance that is marked with heterogeneous enhancement with or
without bone destruction.
PMID- 28512045
TI - Early Diagnosis of Delayed Cerebral Ischemia: Possible Relevance for Inflammatory
Biomarkers in Routine Clinical Practice?
AB - BACKGROUND: Delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH)
is one of the main causes of neurologic deterioration. However, it frequently
evades timely detection. Early identification and effective reversal may improve
the clinical outcome. In this prospective study, we evaluate several serum
inflammatory markers after aneurysmal SAH with regard to the occurrence of DCI.
METHODS: On days 1, 4, 7, 10, and 14 after SAH, leucocyte count, C-reactive
protein, interleukin 6, E-selectin, matrix metallopeptidase 9, intercellular
adhesion molecule 1, and leukemia inhibitory factor were assessed in patients'
serum samples. Using a Cox regression model (SPSS 21.0), associations of baseline
parameters, maximum and delta (maximum minus baseline) values with occurrence of
DCI were evaluated. RESULTS: Considering the assessed parameters, leucocyte count
(high baseline and delta values) matches most closely with occurrence of DCI.
Although baseline levels of C-reactive protein are also associated with
occurrence of DCI, neither maximum (only on a borderline level) nor delta levels
do so. CONCLUSIONS: Our data analysis identified leucocyte count as the parameter
most likely associated with occurrence of DCI. However, because of its lack of
specificity leucocyte count, it cannot be used as a biomarker. As hypothesized
earlier, the results indicate a possible involvement of the inflammatory reaction
after aneurysmal SAH in the pathomechanism of DCI.
PMID- 28512046
TI - Risk Factors for Preoperative Seizures and Loss of Seizure Control in Patients
Undergoing Surgery for Metastatic Brain Tumors.
AB - OBJECTIVE: Metastatic brain tumors are the most common brain tumors in adults.
Patients with metastatic brain tumors have poor prognoses with median survival of
6-12 months. Seizures are a major presenting symptom and cause of morbidity and
mortality. In this article, risk factors for the onset of preoperative seizures
and postoperative seizure control are examined. METHODS: Adult patients who
underwent resection of one or more brain metastases at a single institution
between 1998 and 2011 were reviewed retrospectively. RESULTS: Of 565 patients,
114 (20.2%) patients presented with seizures. Factors independently associated
with preoperative seizures were preoperative headaches (P = 0.044), cognitive
deficits (P = 0.031), more than 2 intracranial metastatic tumors (P = 0.013),
temporal lobe location (P = 0.031), occipital lobe location (P = 0.010), and bone
involvement by tumor (P = 0.029). Factors independently associated with loss of
seizure control after surgical resection were preoperative seizures (P = 0.001),
temporal lobe location (P = 0.037), lack of postoperative chemotherapy (P =
0.010), subtotal resection of tumor (P = 0.022), and local recurrence (P =
0.027). At last follow-up, the majority of patients (93.8%) were seizure-free.
Thirty patients (5.30%) in total had loss of seizure control, and only 8 patients
(1.41%) who did not have preoperative seizures presented with new-onset seizures
after surgical resection of their metastases. CONCLUSIONS: The brain is a common
site for metastases from numerous primary cancers, such as breast and lung. The
identification of factors associated with onset of preoperative seizures as well
as seizure control postoperatively could aid management strategies for patients
with metastatic brain tumors. Patients with preoperative seizures who underwent
resection tended to have good seizure control after surgery.
PMID- 28512047
TI - Preoperative Planning of the Lateral Entry Point Is Necessary in Percutaneous L5
Vertebroplasty.
AB - OBJECTIVE: To compare treatment outcomes and complications between the computer
assisted preoperative planning of lateral entry approach and the traditional
approach for L5 percutaneous vertebroplasty. METHODS: In this prospective
randomized clinical study performed from January 2008 to December 2014, 68
patients scheduled for L5 percutaneous vertebroplasty were divided at random into
group A, in which the traditional transpedicle approach was used, and group B, in
which the computer-assisted lateral entry point approach was used. A visual
analog scale and Oswestry Disability Index were evaluated preoperatively,
postoperatively, and at the latest follow-up. RESULTS: Patient demographics were
similar in the 2 groups. The mean duration of follow-up was 65 months. The mean
distance between the entry point and the midline was 3.05 +/- 0.5 cm in group A
and 7.04 +/- 0.7 cm in group B. The mean inclination angle measured on the
preoperative axial image was 17.1 +/- 3.4 degrees in group A and 41 +/- 3.8
degrees in group B. Clinical outcomes were comparable in the 2 groups; however,
cement leakage was significantly greater in group A (P < 0.001). CONCLUSIONS:
Owing to the hemispherical morphology and convergent pedicle axis of the L5
vertebrae, a more lateral skin entry point and convergent angle of the puncture
needle should be emphasized to reach the optimal point according to the
preoperative assessment. The approach involving computer-assisted preoperative
planning of the lateral entry point was associated with a higher rate of
bilateral cement infiltration with fewer complications.
PMID- 28512048
TI - Combined Hyperactive Dysfunction Syndrome of the Cranial Nerves: A Retrospective
Systematic Study of Clinical Characteristics in 44 Patients.
AB - BACKGROUND: Combined hyperactive dysfunction syndrome (HDS) is defined as the
combination symptoms arising from overactivity in cranial nerves, specifically,
trigeminal neuralgia (TN), hemifacial spasm (HFS), and glossopharyngeal neuralgia
(GPN), without an obvious explanatory structural lesion. This study
retrospectively analyzes the clinical characteristics of combined HDS treated
with microvascular decompression (MVD) in a single institution. METHODS: A total
of 1450 patients with HDS were treated with MVD in our department during a 10
year period, among which 44 cases of combined HDS were identified. Clinical
records and follow-ups were reviewed. RESULTS: Combined HDS comprised 3.03%
(44/1450) of all HDS in our series, with female predominance compared with single
HDS (P = 0.002), including combined TN-HFS (14 cases), combined TN-GPN (26
cases), bilateral TN (2 cases), and combined TN-HFS-GPN (2 cases). The average
age at diagnosis of patients with combined HDS (60.9 years) was significantly
older than that of patients with single HDS (53.5 years) (P = 0.035).
Hypertension was closely associated with the prevalence of combined HDS compared
with single HDS (P = 0.009). The curative rate was 97.7% (43/44) after MVD, and
the recurrence rate was 3.33%. The incidence rates of postoperative cardiac,
pulmonary, thromboembolic, and delirium complications were higher in combined HDS
than in single HDS (P < 0.05). CONCLUSIONS: Combined HDS is a rarely occurring
syndrome usually observed in older females, and the most common types are
combined TN-GPN and combined TN-HFS. Age and gender seemed to be causes for
developing combined HDS, and MVD shows potential as a favorable treatment choice.
PMID- 28512049
TI - Space-Occupying Tumor Bed Cysts as a Complication of Modern Treatment for High
Grade Glioma.
AB - BACKGROUND: The management of high-grade glioma (HGG) has been affected by recent
landmark trials and is now more proactive. More aggressive treatment leads to
hospitalization due to side effects, however. Space-occupying tumor bed cysts
have been described, but not systematically assessed. We sought to analyze this
complication in a contemporary HGG cohort. METHODS: We performed a retrospective
review of patients with HGG treated between 2007 and 2013, identified patients
with space-occupying tumor bed cysts, and reviewed their hospital notes for
relevant variables. Statistical analyses were performed, and odds ratios (ORs)
with 95% confidence intervals (CIs) were calculated. RESULTS: Tumor bed cysts
were found in 12 of 282 patients (4%). The main symptoms were increased
intracranial pressure (n = 11), new focal deficits (n = 6), and pseudomeningocele
(n = 3), presenting at a median of 19 days since the last resection. Cysts were
treated with cystoperitoneal (n = 7) and ventriculoperitoneal (n = 5) shunts,
resulting in clinical benefit in 75% of those treated. Intraoperative opening of
ventricles is a risk factor, with an OR of 39.339. We propose a classification
system comprising 3 cyst types: isolated cyst, cyst with local cerebrospinal
fluid (CSF) disturbance, and cyst with global CSF disturbance. CONCLUSIONS: In
modern neuro-oncology, the rate of tumor bed cysts complicating HGG management
appears stable compared with historical data. Shunt implantation is feasible and
effective. We propose a classification system as a common data element for
comparison across future studies.
PMID- 28512050
TI - Assessing the Role of Preoperative Embolization in the Surgical Management of
Cerebral Arteriovenous Malformations.
AB - BACKGROUND: Preoperative embolization is established as an advantageous adjunct
in multimodality treatment of cerebral arteriovenous malformations (AVMs).
However, the benefit of preoperative embolization in AVMs with favorable surgical
risk profile is debatable, because it has yet to be supported by evidence in
comparative studies. In this study, we assessed outcome of surgically treated
patients in a comparative setting. METHODS: Our institutional AVM database of
retrospectively and prospectively collected data between 1990 and 2015 was
reviewed. Patients with complete clinical data who underwent surgical resection
for AVMs were included. We performed a 1:1 ratio propensity score match for
baseline variables that differed between patients with or without preoperative
embolization. Differences in surgical risk and outcomes were evaluated between
these 2 groups. RESULTS: AVM size, eloquence, deep drainage, middle cerebral
artery feeder, and ruptured presentation differed significantly between the 2
groups. Forty-eight patients without preoperative embolization were matched to 48
with embolization, with no significant differences in baseline variables or AVM
characteristics between the 2 groups. We found no significant differences in AVM
obliteration and postoperative modified Rankin Scale (mRS) score between
embolized and nonembolized patients, respectively. Change in mRS score from
preoperative score was also not significant, although more embolized patients had
a decline in mRS score. Secondary outcome measures including duration of surgery
(P = 0.172), intraoperative bleeding (P = 0.280), duration of hospitalization (P
= 0.368), and postoperative symptoms were also similar between both groups.
CONCLUSIONS: Our data do not support substantial benefit of preoperative
embolization for patients with a favorable surgical risk profile. Because of
risks and costs with this intervention, the prudent use of preoperative
embolization should be individually considered.
PMID- 28512052
TI - Cystic Dilation of the Ventriculus Terminalis: Report of 6 Surgical Cases Treated
with Cyst-Subarachnoid Shunting Using a T-Catheter.
AB - BACKGROUND: Cystic dilation of the ventriculus terminalis (CDVT) is a rare
anatomic variation that and may become symptomatic. Literature regarding CDVT is
limited, and thus the clinical characteristics and management strategy of CDVT
are unclear. Here we report 6 cases of CDVT seen in our institution, and provide
a review of the current literature. METHODS: The study cohort comprised 6
patients with CDVT seen at Beijing Tiantan Hospital between September 2010 and
June 2015. All 6 patients were managed surgically. Data on age, sex, clinical
presentation, radiologic features, operative methods, and surgical outcomes were
reviewed retrospectively. We evaluated the clinical outcomes and postoperative
radiologic changes of these patients and compared them with findings of similar
previous reports. RESULTS: All 6 patients were female, with a median age of 50.0
years (interquartile range [IQR], 25.8-54.0 years). Surgical management of cyst
subarachnoid shunting using T-catheter after myelotomy was successfully performed
in all patients. During an average follow-up of 41 months, relief of clinical
symptoms, especially low-back pain and sciatica, were observed in all 6 patients.
No patients experienced symptom recurrence during follow-up, and postoperative
magnetic resonance imaging revealed no regrowth of the lesion. Patients with
focal neurologic deficits and sphincter disorders also achieved symptom relief
from the procedure. CONCLUSIONS: CDVT is an extremely rare cause of conus
medullaris syndrome with an unclear treatment strategy. Our successful surgical
management of 6 cases through cystic-subarachnoid shunting using a T-catheter for
CDVT drainage provides a potential option for treating CDVT.
PMID- 28512051
TI - Membranectomy in Chronic Subdural Hematoma: Meta-Analysis.
AB - OBJECTIVE: Initial management strategies of chronic subdural hematoma (cSDH) are
controversial and range from bedside twist-drill or burr-hole drainage to
craniotomy with membranectomy (CWM). We aim to 1) perform a meta-analysis of the
available data on the outcomes of CWM for treatment of cSDH in published English
language literature and 2) evaluate collective outcomes of CWM with respect to
morbidity, mortality, and recurrence rates. METHODS: A search of English-language
literature performed in PubMed, Ovid, and Cochrane databases using key words
("subdural hematoma" or "chronic subdural hematoma") and ("membrane" or
"membranectomy") from inception to December 2016 was conducted. Studies reporting
outcomes of CWM in cSDH were included. Mortality, morbidity, follow-up duration,
and recurrence rate data were extracted and analyzed. Pooled estimates and
confidence intervals (CIs) were calculated for all outcomes using a random
effects model. RESULTS: Of 301 articles found, 17 articles containing 5369
patients met our eligibility criteria. Mean follow-up duration ranged from 1-30.8
months. Collective mean mortality and morbidity rates were 3.7% and 6.9%,
respectively (95% CI 2-5.4% and 2.1-11.6%; P < 0.001 and P = 0.004). The
collective mean recurrence rate was 7.6% (95% CI: 5%-10.2%; P < 0.001).
CONCLUSIONS: Clinical data on outcomes of CWM in cSDH are limited to single
institutional analyses, with considerable variation in recurrence rates and
follow-up time. The rates we reported are comparable with the 5% mortality and 3%
12% morbidity rates and lower than the 10%-21% recurrence rate in the literature
for burr holes or craniotomy without membranectomy. This meta-analysis provides
an in-depth analysis of available data and reviews reported outcomes.
PMID- 28512054
TI - Synthesis and characterization of psyllium seed mucilage grafted with N,N
methylene bisacrylamide.
AB - Psyllium seed polysaccharide was modified to investigate its use as
multifunctional pharmaceutical excipient. The objective of this study was
isolation of psyllium seed polysaccharide and crosslinking with acrylic acid
using N,N-methylene bisacrylamide and its characterization. Acrylic acid was used
as monomer and ammonium persulfate as initiator. A full factorial design was
employed to optimize the crosslinking. The modified polysaccharide was
characterized by FTIR, DSC, PXRD, loss on drying, pH, viscosity, micromeritics
properties and swelling studies in 0.1N HCl, 0.5N NaOH, phosphate buffer pH 6.8.
It was observed that swelling of crosslinked polysaccharide increased with
decreased concentration of monomer and increasing concentration of crosslinker.
Greater degree of grafting was observed with increase in crosslinker and monomer
concentration. Dispersions of 1% w/v of PPS and APPS show pseudoplastic behavior.
No clinical signs of toxicity were evident in repeat dose toxicity studies
conducted in rats. Administration of up to 350mg/kg/day of APPS was well
tolerated by the animals. Modification of psyllium via graft copolymerization and
network formation with the crosslinker, improved the property profile and utility
of psyllium polysaccharide. The modified polysaccharide can be used for designing
controlled release drug delivery systems due to its swelling ability.
PMID- 28512053
TI - Effect of chitosan and coagulation factors on the wound repair phenotype of
bioengineered blood clots.
AB - Controlling the blood clot phenotype in a surgically prepared wound is an
evolving concept in scaffold-guided tissue engineering. Here, we investigated the
effect of added chitosan (80% or 95% Degree of Deacetylation, DDA) or coagulation
factors (recombinant human Factor VIIa, Tissue Factor, thrombin) on inflammatory
factors released by blood clots. We tested the hypothesis that 80% DDA chitosan
specifically enhances leukotriene B4 (LTB4) production. Human or rabbit whole
blood was combined with isotonic chitosan solutions, coagulation factors, or
lipopolysaccharide, cultured in vitro at 37 degrees C, and after 4hours the serum
was assayed for LTB4 or inflammatory factors. Only 80% DDA chitosan clots
produced around 15-fold more LTB4 over other clots including 95% DDA chitosan
clots. All serum contained high levels of PDGF-BB and CXCL8. Normal clots
produced very low type I cytokines compared to lipopolysaccharide clots, with
even lower IL-6 and IL-12 and more CCL3/CCL4 produced by chitosan clots.
Coagulation factors had no detectable effect on clot phenotype. Conclusion In
blood clots from healthy individuals, 80% DDA chitosan has a unique influence of
inducing more LTB4, a potent neutrophil chemoattractant, with similar production
of PDGF-BB and CXCL8, and lower type I cytokines, compared to whole blood clots.
PMID- 28512055
TI - First plasma and tissue pharmacokinetic study of the YSNSG cyclopeptide, a new
integrin antagonist, using microdialysis.
AB - The YSNSG peptide is a synthetic peptide targeting alphavbeta3 integrin. This
peptide exhibits promising activity in vitro and in vivo against melanoma. To
determine pharmacokinetic parameters and predictive active doses in the central
nervous system (CNS) and subcutaneous tissue (SC), we conducted microdialysis
coupled with pharmacokinetic modeling and Monte Carlo simulation. After a
recovery period of surgical procedures, a microdialysis probe was inserted in the
caudate and in subcutaneous tissue. Plasma samples and dialysates collected 5h
after YSNSG intravenous administration (10mg/kg) were analyzed by UPLC-MS/MS. A
nonlinear mixed-effect modeling approach implemented in Monolix(r) 2016R1 was
performed. Model selection and evaluation were based on the usual diagnostic
plot, precision and information criteria. The primary plasma and tissue
pharmacokinetic parameters were comparable with those of other integrin
antagonists, such as cilengitide or ATN-161. Tissue/plasma and brain/plasma area
under the curve (AUC) ratio were 66.2+/-21.6% and 3.6+/-4.7%, respectively. Two
models of 2-compartments with an additional microdialysis compartment,
parameterized as rate constants (k for elimination, k12/k21 and k13/k31 for
distribution) and volumes (central V1 and peripheral microdialysis compartment
V3) with zero-order input were selected to describe the dialysate concentrations
in CNS and SC. The inter-individual variability (IIV) was described by
exponential terms, and residual variability was described by a combined additive
and proportional error model. Individual AUC (plasma and tissues) values were
derived for each animal using the Empirical-Bayes-Estimates of the individual
parameters. The regimens needed to achieve an in vitro predetermined target
concentration in tissues were studied by Monte Carlo simulations using Monolix(r)
2016R1. YSNSG pharmacokinetic parameters show promising results in terms of
subcutaneous disposition. Further investigations into such processes as
encapsulation and intratumoral disposition are currently being conducted.
PMID- 28512056
TI - Combined proportional and additive residual error models in population
pharmacokinetic modelling.
AB - INTRODUCTION: In pharmacokinetic modelling, a combined proportional and additive
residual error model is often preferred over a proportional or additive residual
error model. Different approaches have been proposed, but a comparison between
approaches is still lacking. METHODS: The theoretical background of the methods
is described. Method VAR assumes that the variance of the residual error is the
sum of the statistically independent proportional and additive components; this
method can be coded in three ways. Method SD assumes that the standard deviation
of the residual error is the sum of the proportional and additive components.
Using datasets from literature and simulations based on these datasets, the
methods are compared using NONMEM. RESULTS: The different coding of methods VAR
yield identical results. Using method SD, the values of the parameters describing
residual error are lower than for method VAR, but the values of the structural
parameters and their inter-individual variability are hardly affected by the
choice of the method. CONCLUSION: Both methods are valid approaches in combined
proportional and additive residual error modelling, and selection may be based on
OFV. When the result of an analysis is used for simulation purposes, it is
essential that the simulation tool uses the same method as used during analysis.
PMID- 28512057
TI - Normative morphometric data for cerebral cortical areas over the lifetime of the
adult human brain.
AB - Proper normative data of anatomical measurements of cortical regions, allowing to
quantify brain abnormalities, are lacking. We developed norms for regional
cortical surface areas, thicknesses, and volumes based on cross-sectional MRI
scans from 2713 healthy individuals aged 18 to 94 years using 23 samples provided
by 21 independent research groups. The segmentation was conducted using
FreeSurfer, a widely used and freely available automated segmentation software.
Models predicting regional cortical estimates of each hemisphere were produced
using age, sex, estimated total intracranial volume (eTIV), scanner manufacturer,
magnetic field strength, and interactions as predictors. The explained variance
for the left/right cortex was 76%/76% for surface area, 43%/42% for thickness,
and 80%/80% for volume. The mean explained variance for all regions was 41% for
surface areas, 27% for thicknesses, and 46% for volumes. Age, sex and eTIV
predicted most of the explained variance for surface areas and volumes while age
was the main predictors for thicknesses. Scanner characteristics generally
predicted a limited amount of variance, but this effect was stronger for
thicknesses than surface areas and volumes. For new individuals, estimates of
their expected surface area, thickness and volume based on their characteristics
and the scanner characteristics can be obtained using the derived formulas, as
well as Z score effect sizes denoting the extent of the deviation from the
normative sample. Models predicting normative values were validated in
independent samples of healthy adults, showing satisfactory validation R2.
Deviations from the normative sample were measured in individuals with mild
Alzheimer's disease and schizophrenia and expected patterns of deviations were
observed.
PMID- 28512058
TI - Downregulation of miR-224 and let-7i contribute to cell survival and
chemoresistance in chronic myeloid leukemia cells by regulating ST3GAL IV
expression.
AB - Acquired resistance to imatinib is frequently associated with poor clinical
outcome of chronic myeloid leukemia (CML) patient. To date, evidence indicates
that protein glycosylation and its upstream regulators might be implicated in
tumorigenesis and chemoresistance occurrence. In current study we initially
explored N-glycan profiles on the surface of CML cell lines and bone marrow
mononuclear cells (BMMC) of CML patients by using mass spectrometry (MS)
analysis. An elevated sialylation was detected in K562R cells (CML cells with
imatinib resistance phenotype) compare to K562 cells. By quantitative real time
PCR (qRT-PCR) and western blotting analysis we observed that imatinib resistant
K562R cells exhibited marked high levels of CMP-N-acetylneuraminate-beta
galactosamide-alpha-2,3-sialyltransferase (ST3Gal IV) as compared to imatinib
sensitive K562 cells. Further studies revealed that manipulated expression of
ST3GAL IV led to the significant alterations of cell cycle distribution,
apoptotic signal, cell proliferation and the effectiveness of imatinib treatment.
Using microRNA array, miRNA database searching and luciferase reporter assay, we
identified that miR-224 and let-7i directly regulate the expression of ST3GAL IV
gene. Moreover, engineered expression of miR-224 and let-7i in K562 and K562R
cells could significantly affect ST6Gal IV-induced proliferation rate and drug
resistance. Thus we propose that miR-224 and let-7i regulate the proliferation
and chemosensitivity of CML cells probably via targeting ST3GAL IV.
PMID- 28512059
TI - Genome-scale metabolic network of Cordyceps militaris useful for comparative
analysis of entomopathogenic fungi.
AB - The first genome-scale metabolic network of Cordyceps militaris (iWV1170) was
constructed representing its whole metabolisms, which consisted of 894
metabolites and 1,267 metabolic reactions across five compartments, including the
plasma membrane, cytoplasm, mitochondria, peroxisome and extracellular space. The
iWV1170 could be exploited to explain its phenotypes of growth ability,
cordycepin and other metabolites production on various substrates. A high number
of genes encoding extracellular enzymes for degradation of complex carbohydrates,
lipids and proteins were existed in C. militaris genome. By comparative genome
scale analysis, the adenine metabolic pathway towards putative cordycepin
biosynthesis was reconstructed, indicating their evolutionary relationships
across eleven species of entomopathogenic fungi. The overall metabolic routes
involved in the putative cordycepin biosynthesis were also identified in C.
militaris, including central carbon metabolism, amino acid metabolism (glycine, l
glutamine and l-aspartate) and nucleotide metabolism (adenosine and adenine).
Interestingly, a lack of the sequence coding for ribonucleotide reductase
inhibitor was observed in C. militaris that might contribute to its over
production of cordycepin.
PMID- 28512060
TI - Characterization and phylogenetic analysis of complete mitochondrial genomes for
two desert cyprinodontoid fishes, Empetrichthys latos and Crenichthys baileyi.
AB - The Pahrump poolfish (Empetrichthys latos) and White River springfish
(Crenichthys baileyi) are small-bodied teleost fishes (order Cyprinodontiformes)
endemic to the arid Great Basin and Mojave Desert regions of western North
America. These taxa survive as small, isolated populations in remote streams and
springs and evolved to tolerate extreme conditions of high temperature and low
dissolved oxygen. Both species have experienced severe population declines over
the last 50-60years that led to some subspecies being categorized with protected
status under the U.S. Endangered Species Act. Here we report the first sequencing
of the complete mitochondrial DNA genomes for both E. l. latos and the moapae
subspecies of C. baileyi. Complete mitogenomes of 16,546bp nucleotides were
obtained from two E. l. latos individuals collected from introduced populations
at Spring Mountain Ranch State Park and Shoshone Ponds Natural Area, Nevada, USA,
while a single mitogenome of 16,537bp was sequenced for C. b. moapae. The
mitogenomes of both species contain 13 protein-encoding genes, twenty-two tRNAs,
and two rRNAs (12S and 18S) following the syntenic arrangement typical of
Actinopterygiian fish mitogenomes, as well as D-loop control regions of 858bp for
E. latos and 842bp for C. baileyi moapae. The two E. latos individuals exhibited
only 0.0181% nucleotide sequence divergence across the entire mitogenome,
implying little intraspecific mtDNA genetic variation. Comparative phylogenetic
analysis of the poolfish and springfish mitochondrial genomes to available
mitogenomes of other Cyprinodontoid fishes confirmed the close relationship of
these oviparous Empetrichthys and Crenichthys genera to the viviparous goodeid
fishes of central Mexico, and showed the combined clade of these fishes to be a
sister group to the Profundulidae killifishes. Despite several significant life
history and morphological differences between the Empetrichthyinae and Goodienae,
estimates of evolutionary genetic distances using two partial regions of mtDNA
point to inclusion of the Empetrichthys and Crenichthys genera within the family
Goodeidae along with the goodeid fishes of central Mexico.
PMID- 28512061
TI - Genetic variants in autophagy associated genes are associated with DNA damage
levels in Chinese population.
AB - Autophagy associated genes (ATGs) played an important role in the repair process
of DNA damage and decreased autophagy may weaken the repair process and aggravate
DNA damage. Based on this, we hypothesized that DNA damage levels might be
modified by genetic variants in autophagy associated genes. In order to validate
our hypothesis, 307 subjects were recruited from three different cities (Zhuhai,
Wuhan and Tianjin) in China. Demographic data, individual 24-h PM2.5 exposure and
peripheral blood DNA damage levels were also detected. Seven potentially
functional polymorphisms in four essential autophagy associated genes (ATG5,
ATG7, ATG8 and ATG13) were screened to evaluate the relationship between the
polymorphisms of autophagy associated genes and DNA damage levels. This
association was assessed by using multivariable linear regression model, age,
sex, smoke and PM2.5 exposure levels were adjusted in each city. We found that
rs12599322 in ATG8 (A>G, beta=0.263, 95% CI: 0.108-0.419, P=8.98*10-4) and
rs7484002 in ATG13 (A>G, beta=0.396, 95% CI: 0.085-0.708, P=0.013) were
significantly associated with higher DNA damage levels. Furthermore, functional
annotations showed that both rs12599322 and rs7484002 located at transcription
factor binding sites (TFBS), indicating that they could regulate the expression
of related genes through TF regulation. Following allelic trend analysis revealed
that the DNA damage levels were significantly aggravated with the increasing
number of risk variants in autophagy associated genes (P for trend: 8.09*10-5).
Our findings suggested that the polymorphisms in ATGs may influence DNA damage
levels in one of the Chinese population.
PMID- 28512062
TI - Hsa-miR-513b-5p suppresses cell proliferation and promotes P53 expression by
targeting IRF2 in testicular embryonal carcinoma cells.
AB - Previous studies have reported the miR-513b is located on the X chromosome and is
preferentially expressed in testis. However, the underlying mechanisms of miR
513b involved in spermatogenesis remains unknown. In this study, we found that
hsa-miR-513b-5p was highly expressed in the testes of infertile males with
maturation arrest compared with normal controls. Overexpression of hsa-miR-513b
5p suppressed testicular embryonal carcinoma (NT2) cell proliferation and induced
apoptosis in vitro, whereas silencing of hsa-miR-513b-5p reversed these effects.
In addition, we found that interferon regulatory transcription factor 2 (IRF2)
was a direct and functional target of hsa-miR-513b-5p. Silencing of endogenous
IRF2 enhanced hsa-miR-513b-5p-mediated effects on cell proliferation in NT2
cells, whereas overexpression of IRF2 reversed these effects. Moreover,
immunoblotting showed that overexpression of hsa-miR-513b-5p or silencing of
endogenous IRF2 could promote the expression of P53. Moreover, overexpression of
hsa-miR-513b-5p in the absence of p53 could also induce cell apoptosis. Together,
our results suggest that hsa-miR-513b-5p suppresses NT2 cell proliferation and
promotes P53 protein expression by targeting IRF2, and abnormal testicular hsa
miR-513b-5p expression may contribute to maturation arrest.
PMID- 28512064
TI - Familial lumps of the lower jaw.
PMID- 28512065
TI - Long-Term Functional and Psychosocial Outcomes After Hypoxic-Ischemic Brain
Injury: A Case-Controlled Comparison to Traumatic Brain Injury.
AB - BACKGROUND: Despite the increasing rate of survival from hypoxic-ischemic brain
injury (HIBI), there is a paucity of evidence on the long-term functional
outcomes after inpatient rehabilitation among these nontrauma patients compared
to patients with traumatic brain injury (TBI). OBJECTIVES: To compare functional
and psychosocial outcomes of patients with HIBI to those of case-matched patients
with TBI 4-11 years after brain insult. DESIGN: Retrospective, matched case
controlled study. METHODS: Data at the time of rehabilitation admission and
discharge were collected as part of a larger acquired brain injury (ABI) database
at Toronto Rehabilitation Institute (TRI) between 1999 and 2009. This study
consisted of 11 patients with HIBI and 11 patients with TBI that attended the
neuro-rehabilitation day program at TRI during a similar time frame and were
matched on age, admission Functional Independence Measure (FIM) scores, and acute
care length of stay (ALOS). At 4-11 years following brain insult, patients were
reassessed using the FIM, Disability Rating Scale (DRS), Personal Health
Questionnaire Depression Scale (PHQ-9), and the Mayo-Portland Adaptability
Inventory 4 (MPAI-4). RESULTS: At follow-up, patients with HIBI had significantly
lower FIM motor and cognitive scores than patients with TBI (75.3 +/- 20.6 versus
88.1 +/- 4.78, P < .05, and 25.5 +/- 5.80 versus 32.7 +/- 2.54, P <.05,
respectively) despite having a similar time frame postinsult (ie, 4-11 years). In
addition, there were significant differences in motor and total FIM change from
admission to follow-up between HIBI and TBI patients (P < .05). Patients with
HIBI also had significantly lower scores on the DRS, PHQ-9, and total MPAI-4 at
follow-up (P < .05). CONCLUSIONS: The study results suggest that patients with
HIBI achieve less long-term functional improvements compared to patients with
TBI. Further research is warranted to compare the components of inpatient
rehabilitation while adjusting for demographics and clinical characteristics
between these 2 groups of patients. LEVEL OF EVIDENCE: III.
PMID- 28512063
TI - Influence of delayed gadolinium enhanced MRI of cartilage (dGEMRIC) protocol on
T2-mapping: is it possible to comprehensively assess knee cartilage composition
in one post-contrast MR examination at 3 Tesla?
AB - OBJECTIVE: To evaluate the possibility of assessing knee cartilage with T2
mapping and delayed gadolinium enhanced magnetic resonance imaging (MRI) of
cartilage (dGEMRIC) in one post-contrast MR examination at 3 Tesla (T). DESIGN:
T2 mapping was performed in 10 healthy volunteers at baseline; directly after
baseline; after 10 min of cycling; and after 90 min delay, and in 16
osteoarthritis patients before and after intravenous administration of a double
dose gadolinium dimeglumine contrast agent, reflecting key dGEMRIC protocol
elements. Differences in T2 relaxation times between each timepoint and baseline
were calculated for 6 cartilage regions using paired t tests or Wilcoxon signed
rank tests and the smallest detectable change (SDC). RESULTS: After cycling, a
significant change in T2 relaxation times was found in the lateral weight-bearing
tibial plateau (+1.0 ms, P = 0.04). After 90 min delay, significant changes were
found in the lateral weight-bearing femoral condyle (+1.2 ms, P = 0.03) and the
lateral weight-bearing tibial plateau (+1.3 ms, P = 0.01). In these regions of
interests (ROIs), absolute differences were small and lower than the
corresponding SDCs. T2-mapping after contrast administration only showed
statistically significantly lower T2 relaxation times in the medial posterior
femoral condyle (-2.4 ms, P < 0.001) with a change exceeding the SDC. CONCLUSION:
Because dGEMRIC protocol elements resulted in only small differences in T2
relaxation times that were not consistent and lower than the SDC in the majority
of regions, our results suggest that T2-mapping and dGEMRIC can be performed
reliably in a single imaging session to assess cartilage biochemical composition
in knee osteoarthritis (OA) at 3 T.
PMID- 28512066
TI - Use of Electroencephalography Brain-Computer Interface Systems as a
Rehabilitative Approach for Upper Limb Function After a Stroke: A Systematic
Review.
AB - BACKGROUND: Brain-computer interface (BCI) systems have been suggested as a
promising tool for neurorehabilitation. However, to date, there is a lack of
homogeneous findings. Furthermore, no systematic reviews have analyzed the degree
of validation of these interventions for upper limb (UL) motor rehabilitation
poststroke. OBJECTIVES: The study aims were to compile all available studies that
assess an UL intervention based on an electroencephalography (EEG) BCI system in
stroke; to analyze the methodological quality of the studies retrieved; and to
determine the effects of these interventions on the improvement of motor
abilities. TYPE: This was a systematic review. LITERATURE SURVEY: Searches were
conducted in PubMed, PEDro, Embase, Cumulative Index to Nursing and Allied
Health, Web of Science, and Cochrane Central Register of Controlled Trial from
inception to September 30, 2015. METHODOLOGY: This systematic review compiles all
available studies that assess UL intervention based on an EEG-BCI system in
patients with stroke, analyzing their methodological quality using the Critical
Review Form for Quantitative Studies, and determining the grade of recommendation
of these interventions for improving motor abilities as established by the Oxford
Centre for Evidence-based Medicine. The articles were selected according to the
following criteria: studies evaluating an EEG-based BCI intervention; studies
including patients with a stroke and hemiplegia, regardless of lesion origin or
temporal evolution; interventions using an EEG-based BCI to restore functional
abilities of the affected UL, regardless of the interface used or its combination
with other therapies; and studies using validated tools to evaluate motor
function. SYNTHESIS: After the literature search, 13 articles were included in
this review: 4 studies were randomized controlled trials; 1 study was a
controlled study; 4 studies were case series studies; and 4 studies were case
reports. The methodological quality of the included papers ranged from 6 to 15,
and the level of evidence varied from 1b to 5. The articles included in this
review involved a total of 141 stroke patients. CONCLUSIONS: This systematic
review suggests that BCI interventions may be a promising rehabilitation approach
in subjects with stroke. LEVEL OF EVIDENCE: II.
PMID- 28512067
TI - Optimal implantation is the way to prevent scaffold thrombosis: a hypothesis to
be tested.
PMID- 28512068
TI - Potentially increased incidence of scaffold thrombosis in patients treated with
Absorb BVS who terminated DAPT before 18 months.
AB - AIMS: The aim of this study was to investigate the impact of dual antiplatelet
therapy (DAPT) termination on late and very late scaffold thrombosis (ScT) in
patients treated with the Absorb bioresorbable vascular scaffold (BVS). METHODS
AND RESULTS: Data from the registries of three centres were pooled (808
patients). To investigate the effect of DAPT termination on ScT after a minimum
of six months, we selected a subgroup ("DAPT study cohort" with 685 patients)
with known DAPT status >6 months and excluded the use of oral anticoagulants and
early ScT. In this cohort, definite/probable ScT incidence for the period on DAPT
was compared to ScT incidence after DAPT termination. ScT incidence was 0.83
ScT/100 py with 95% confidence interval (CI): 0.34-1.98. After DAPT termination,
the incidence was higher (1.77/100 py; 95% CI: 0.66-4.72), compared to the
incidence on DAPT (0.26/100 py, 95% CI: 0.04-1.86; p=0.12) and increased within
the month after DAPT termination (6.57/100 py, 95% CI: 2.12-20.38; p=0.01). No
very late ScT occurred in patients who continued on DAPT for a minimum of 18
months. CONCLUSIONS: The incidence of late and very late definite/probable ScT
was acceptable. The incidence was low while on DAPT but potentially higher when
DAPT was terminated before 18 months.
PMID- 28512069
TI - Optical coherence tomography findings: insights from the "randomised multicentre
trial investigating angiographic outcomes of hybrid sirolimus-eluting stents with
biodegradable polymer compared with everolimus-eluting stents with durable
polymer in chronic total occlusions" (PRISON IV) trial.
AB - AIMS: The PRISON IV trial investigated the next-generation sirolimus-eluting
stent (SES) with ultra-thin struts and biodegradable polymer against the second
generation everolimus-eluting stent (EES) with thin struts and durable polymer in
patients with successfully recanalised chronic total occlusions (CTO). In this
study, we examined the secondary optical coherence tomography endpoints. METHODS
AND RESULTS: The main PRISON IV trial randomised 330 patients to either SES or
EES. At nine months, 281 (85%) patients underwent repeat angiography. Of these,
60 consecutive patients received optical coherence tomography divided over both
stent groups. The mean number of struts analysed was 750+/-337 and 633+/-358 in
SES and EES patients, respectively (p=0.07). The minimal lumen area, minimal
stent area, maximal neointima area and neointimal thickness were comparable
between the groups (4.8+/-2.1 and 4.4+/-1.5 mm2; 5.3+/-1.8 and 5.3+/-1.4 mm2;
2.5+/-2.0 and 2.2+/-1.5 mm2; 0.7+/-1.7 and 0.4+/-0.2 mm). The percentage of
uncovered struts was higher with EES (6.2+/-7.5% and 11.9+/-13.4%, p=0.04),
whereas the percentage of malapposed struts and mean number of coronary
evaginations were significantly higher with SES (2.9+/-4.0% and 1.2+/-2.4%,
p=0.02; 18.5+/-17.7 and 5.3+/-3.1, p=0.004). CONCLUSIONS: The optical coherence
tomography findings of this substudy demonstrated improved strut coverage with
ultra-thin strut SES with bioresorbable polymer compared to thin-strut EES with
durable polymer in CTO. On the other hand, SES showed a higher rate of stent
strut malappositon and coronary evaginations. The clinical relevance of these
findings remains to be demonstrated.
PMID- 28512070
TI - Very late scaffold thrombosis: is prolonged DAPT the answer?
PMID- 28512071
TI - Ethical and legal challenges of vaccines and vaccination: Reflections.
AB - Vaccines and vaccination have emerged as key medical scientific tools for
prevention of certain diseases. Documentation of the history of vaccination shows
that the initial popular resistance to universal vaccination was based on false
assumptions and eventually gave way to acceptance of vaccines and trust in their
ability to save lives. The successes of the global eradication of smallpox, and
now of polio, have only strengthened the premier position occupied by vaccines in
disease prevention. However, the success of vaccines and public trust in their
ability to eradicate disease are now under challenge, as increasing numbers of
people refuse vaccination, questioning the effectiveness of vaccines and the need
to vaccinate.
PMID- 28512072
TI - Lessons learnt in Japan from adverse reactions to the HPV vaccine: a medical
ethics perspective.
AB - The human papillomavirus (HPV) vaccine has been linked to a number of serious
adverse reactions. The range of symptoms is diverse and they develop in a multi
layered manner over an extended period of time. The argument for the safety and
effectiveness of the HPV vaccine overlooks the following flaws: (i) no
consideration is given to the genetic basis of autoimmune diseases, and arguments
that do not take this into account cannot assure the safety of the vaccine; (ii)
the immune evasion mechanisms of HPV, which require the HPV vaccine to maintain
an extraordinarily high antibody level for a long period of time for it to be
effective, are disregarded; and (iii) the limitations of effectiveness of the
vaccine. We also discuss various issues that came up in the course of developing,
promoting and distributing the vaccine, as well as the pitfalls encountered in
monitoring adverse events and epidemiological verification.
PMID- 28512073
TI - Identifying ethical issues in the development of vaccines and in vaccination.
AB - Vaccines are a widely accepted public health intervention. They are also a
profitable tool for pharmaceutical companies manufacturing vaccines. There are
many vaccines in the pipeline, for various diseases, or as combination vaccines
for several diseases. However, there is also a growing concern about vaccines and
the manner in which they are developed and approved by the authorities. Approvals
are fast tracked and adverse events and serious adverse events following
vaccination are seldom reported once the vaccine gets its marketing approval.
Thus, vaccines have been clouded with many controversies and their use as a
public health tool to prevent diseases is constantly under challenge.
PMID- 28512074
TI - An idea whose time has come: Compensation for vaccine-related injuries and death
in India.
AB - This paper emphasises the urgent need for a compensation policy for those
affected by adverse events following immunisation in India. In the absence of
such a mechanism in the country, people claim compensation by taking recourse to
tort law and have to face the ensuing uncertainty and challenges with regard to
the award of compensation. The paper argues that people should be provided
compensation in the event of death and serious adverse events following
compulsory immunisation, irrespective of whether there is a causal association
between the adverse event and the vaccine, on the basis of no fault compensation.
PMID- 28512075
TI - Public trust in vaccination: an analytical framework.
AB - While vaccination is one of the most successful public health interventions,
there has always been a parallel movement against vaccines. Apart from scientific
factors, the uptake of vaccinations is influenced by historical, political,
sociocultural and economic factors. In India, the health system is struggling
with logistical weaknesses in taking vaccination to the remotest corners; while
on the other hand, some people in places where vaccination is available resist
it. Unwillingness to be vaccinated is a growing problem in the developed world.
This trend is gradually emerging in several parts of India as well. Other
factors, such as heightened awareness of the profit motives of the vaccine
industry, conflicts of interest among policy-makers, and social, cultural and
religious considerations have eroded the people's trust in vaccination. This
paper develops an analytical framework to assess trust in vaccination. The
framework considers trust in vaccination from four perspectives - trust in the
health system, the vaccine policy, vaccination providers and specific vaccines.
The framework considers specific issues involved in vaccination trust, including
the increasing scepticism towards medical technology, perceptions of conflicts of
interest in the vaccine policy, and of lack of transparency and openness, the
presence of strong alternative schools of thought, influence of the social media.
The paper will conclude by arguing that engaging with communities and having a
dialogue about the vaccination policy is an ethical imperative.
PMID- 28512076
TI - Considering the "public" in public health: popular resistance to the Smallpox
Eradication Programme in India.
AB - Public health initiatives, including large-scale vaccination and disease
eradication programmes, regularly pit the rights of the individual against
broader benefits to society. At times, the public resists such initiatives, with
the World Health Organisation's Smallpox Eradication Programme (SEP) in India
being a case in point. Here, we critically investigate resistance to smallpox
vaccines in India and argue that while the SEP successfully eradicated a global
killer; individuals were stripped of human rights through coercion, forcible
vaccination and quarantine. In many cases, resistance to vaccination was linked
to deep-rooted social, cultural and religious beliefs. Critical points made in
this paper are applicable to contemporary discussions on required vaccinations,
quarantine during the outbreak of diseases and the current campaign to eradicate
polio.
PMID- 28512077
TI - Vaccine delivery to disease control: a paradigm shift in health policy.
AB - India's Universal Immunisation Programme (UIP) has resulted in the creation of
infrastructure, human resources and systems for the procurement and delivery of
vaccines. Recently, new vaccines have been added and there are plans for the
introduction of more. However, the outcomes in terms of reduction of the diseases
for which the vaccines are being administered remain ambiguous. This is evident
from the persistent health issues that children continue to experience, despite
immunisation. This situation raises a fundamental ethical question for public
health: vaccinations are one of the tools of disease control, but are they
properly aligned to the control of disease so as to produce the expected public
health utility or benefit?
PMID- 28512078
TI - Is MCI over emphasising publication for promotion of medical teachers?
AB - Over the past year, there has been constant debate in various journals on the
circular issued by the Medical Council of India (MCI) in September 2015,
regarding the requirements for promotion of teaching faculty. The lack of a time
bound promotion system of medical faculty results in higher stress,
dissatisfaction, lower productivity and quality of life and work. The critics
have highlighted several issues in assessment of publication for teacher's
promotion, eg the exclusion of publications in "electronic-only" journals,
awarding points only to "original research" papers and first or second authors,
listing of indexing databases for journals, categorising journals as national or
international.
PMID- 28512079
TI - Crowdsourced Identification of Possible Allergy-Associated Factors: Automated
Hypothesis Generation and Validation Using Crowdsourcing Services.
AB - BACKGROUND: Hypothesis generation is an essential task for clinical research, and
it can require years of research experience to formulate a meaningful hypothesis.
Recent studies have endeavored to apply crowdsourcing to generate novel
hypotheses for research. In this study, we apply crowdsourcing to explore
previously unknown allergy-associated factors. OBJECTIVE: In this study, we aimed
to collect and test hypotheses of unknown allergy-associated factors using a
crowdsourcing service. METHODS: Using a series of questionnaires, we asked
crowdsourcing participants to provide hypotheses on associated factors for seven
different allergies, and validated the candidate hypotheses with odds ratios
calculated for each associated factor. We repeated this abductive validation
process to identify a set of reliable hypotheses. RESULTS: We obtained two
primary findings: (1) crowdsourcing showed that 8 of the 13 known hypothesized
allergy risks were statically significant; and (2) among the total of 157
hypotheses generated by the crowdsourcing service, 75 hypotheses were
statistically significant allergy-associated factors, comprising the 8 known
risks and 53 previously unknown allergy-associated factors. These findings
suggest that there are still many topics to be examined in future allergy
studies. CONCLUSIONS: Crowdsourcing generated new hypotheses on allergy
associated factors. In the near future, clinical trials should be conducted to
validate the hypotheses generated in this study.
PMID- 28512080
TI - Using Text Messaging in Long-Term Arthroplasty Follow-Up: A Pilot Study.
AB - BACKGROUND: Patient-reported outcome measures (PROMs) and mobile technology have
the potential to change the way patients are monitored following joint
replacement surgery. OBJECTIVE: The aim of this study was to determine the
feasibility of text messaging to record PROMs in long-term follow-up of hip and
knee arthroplasty. Our participants were 17 patients 2-years-plus post hip or
knee arthroplasty attending clinic with a mobile telephone number on record.
METHODS: A simple PROM (Oswestry Very Short Form) was texted to the patient.
Responses were compared to clinical, radiographic, and existing PROM findings.
Patients were interviewed to discover their opinions on this use of texting.
RESULTS: A total of 11 patients engaged with the text messaging. Reasons for not
engaging included wrong numbers, physical barriers, and lack of understanding. A
total of 8 patients attending clinic allowed comparison of text messaging with
clinical findings. The average age was 70 years. A total of 4 patient text
messaging responses matched clinical and radiographic findings; 3 also matched
PROM scores collected in clinic. The 3 patients with mixed responses had abnormal
clinical, radiographic, or PROM findings. One patient's text responses conflicted
with clinical outcome. Analysis of patients' views showed a generally positive
opinion: patients were happy to communicate with surgeons by text. Practical
problems, PROM limitations, and trustworthiness of texting were highlighted.
CONCLUSIONS: Engaging with changing technology creates challenges for patients
and health care professionals. Despite this, our results suggest text messaging
is a promising way to communicate with arthroplasty patients. Earlier integration
of text communication in the patient pathway may be important and needs further
research.
PMID- 28512081
TI - Effects of eHealth Literacy on General Practitioner Consultations: A Mediation
Analysis.
AB - BACKGROUND: Most evidence (not all) points in the direction that individuals with
a higher level of health literacy will less frequently utilize the health care
system than individuals with lower levels of health literacy. The underlying
reasons of this effect are largely unclear, though people's ability to seek
health information independently at the time of wide availability of such
information on the Internet has been cited in this context. OBJECTIVE: We propose
and test two potential mediators of the negative effect of eHealth literacy on
health care utilization: (1) health information seeking and (2) gain in
empowerment by information seeking. METHODS: Data were collected in New Zealand,
the United Kingdom, and the United States using a Web-based survey administered
by a company specialized on providing online panels. Combined, the three samples
resulted in a total of 996 baby boomers born between 1946 and 1965 who had used
the Internet to search for and share health information in the previous 6 months.
Measured variables include eHealth literacy, Internet health information seeking,
the self-perceived gain in empowerment by that information, and the number of
consultations with one's general practitioner (GP). Path analysis was employed
for data analysis. RESULTS: We found a bundle of indirect effect paths showing a
positive relationship between health literacy and health care utilization: via
health information seeking (Path 1), via gain in empowerment (Path 2), and via
both (Path 3). In addition to the emergence of these indirect effects, the direct
effect of health literacy on health care utilization disappeared. CONCLUSIONS:
The indirect paths from health literacy via information seeking and empowerment
to GP consultations can be interpreted as a dynamic process and an expression of
the ability to find, process, and understand relevant information when that is
necessary.
PMID- 28512082
TI - Medical Student Evaluation With a Serious Game Compared to Multiple Choice
Questions Assessment.
AB - BACKGROUND: The gold standard for evaluating medical students' knowledge is by
multiple choice question (MCQs) tests: an objective and effective means of
restituting book-based knowledge. However, concerns have been raised regarding
their effectiveness to evaluate global medical skills. Furthermore, MCQs of
unequal difficulty can generate frustration and may also lead to a sizable
proportion of close results with low score variability. Serious games (SG) have
recently been introduced to better evaluate students' medical skills. OBJECTIVES:
The study aimed to compare MCQs with SG for medical student evaluation. METHODS:
We designed a cross-over randomized study including volunteer medical students
from two medical schools in Paris (France) from January to September 2016. The
students were randomized into two groups and evaluated either by the SG first and
then the MCQs, or vice-versa, for a cardiology clinical case. The primary
endpoint was score variability evaluated by variance comparison. Secondary
endpoints were differences in and correlation between the MCQ and SG results, and
student satisfaction. RESULTS: A total of 68 medical students were included. The
score variability was significantly higher in the SG group (sigma2 =265.4) than
the MCQs group (sigma2=140.2; P=.009). The mean score was significantly lower for
the SG than the MCQs at 66.1 (SD 16.3) and 75.7 (SD 11.8) points out of 100,
respectively (P<.001). No correlation was found between the two test results
(R2=0.04, P=.58). The self-reported satisfaction was significantly higher for SG
(P<.001). CONCLUSIONS: Our study suggests that SGs are more effective in terms of
score variability than MCQs. In addition, they are associated with a higher
student satisfaction rate. SGs could represent a new evaluation modality for
medical students.
PMID- 28512084
TI - GPs use pen and paper after IT systems are shut down as precaution.
PMID- 28512083
TI - The impact of not having enough staff is exhausting and detrimental to patient
care.
PMID- 28512087
TI - Cannabis as medicine.
PMID- 28512086
TI - Two Loci Contribute Epistastically to Heterospecific Pollen Rejection, a
Postmating Isolating Barrier Between Species.
AB - Recognition and rejection of heterospecific male gametes occurs in a broad range
of taxa, although the complexity of mechanisms underlying these components of
postmating cryptic female choice is poorly understood. In plants, the arena for
postmating interactions is the female reproductive tract (pistil), within which
heterospecific pollen tube growth can be arrested via active molecular
recognition and rejection. Unilateral incompatibility (UI) is one such postmating
barrier in which pollen arrest occurs in only one direction of an interspecific
cross. We investigated the genetic basis of pistil-side UI between Solanum
species, with the specific goal of understanding the role and magnitude of
epistasis between UI QTL. Using heterospecific introgression lines (ILs) between
Solanum pennellii and S. lycopersicum, we assessed the individual and pairwise
effects of three chromosomal regions (ui1.1, ui3.1, and ui12.1) previously
associated with interspecific UI among Solanum species. Specifically, we
generated double introgression ('pyramided') genotypes that combined ui12.1 with
each of ui1.1 and ui3.1, and assessed the strength of UI pollen rejection in the
pyramided lines, compared to single introgression genotypes. We found that none
of the three QTL individually showed UI rejection phenotypes, but lines combining
ui3.1 and ui12.1 showed significant pistil-side pollen rejection. Furthermore,
double ILs (DILs) that combined different chromosomal regions overlapping ui3.1
differed significantly in their rate of UI, consistent with at least two genetic
factors on chromosome three contributing quantitatively to interspecific pollen
rejection. Together, our data indicate that loci on both chromosomes 3 and 12 are
jointly required for the expression of UI between S. pennellii and S.
lycopersicum, suggesting that coordinated molecular interactions among a
relatively few loci underlie the expression of this postmating prezygotic
barrier. In addition, in conjunction with previous data, at least one of these
loci appears to also contribute to conspecific self-incompatibility (SI),
consistent with a partially shared genetic basis between inter- and intraspecific
mechanisms of postmating prezygotic female choice.
PMID- 28512088
TI - TRPV4 in the battle of the sexes.
AB - New JGP paper explains sexual dimorphism and tissue-specific activity of TRPV4.
PMID- 28512085
TI - Self reported outcomes and adverse events after medical abortion through online
telemedicine: population based study in the Republic of Ireland and Northern
Ireland.
AB - Objectives To assess self reported outcomes and adverse events after self sourced
medical abortion through online telemedicine.Design Population based
study.Setting Republic of Ireland and Northern Ireland, where abortion is
unavailable through the formal healthcare system except in a few restricted
circumstances.Population 1000 women who underwent self sourced medical abortion
through Women on Web (WoW), an online telemedicine service, between 1 January
2010 and 31 December 2012.Main outcome measures Successful medical abortion: the
proportion of women who reported ending their pregnancy without surgical
intervention. Rates of adverse events: the proportion who reported treatment for
adverse events, including receipt of antibiotics and blood transfusion, and
deaths reported by family members, friends, or the authorities. Care seeking for
symptoms of potential complications: the frequency with which women reported
experiencing symptoms of a potentially serious complication and the proportion
who reported seeking medical attention as advised.Results In 2010-12, abortion
medications (mifepristone and misoprostol) were sent to 1636 women and follow-up
information was obtained for 1158 (71%). Among these, 1023 women confirmed use of
the medications, and follow-up information was available for 1000. At the time
women requested help from WoW, 781 (78%) were <7 weeks pregnant and 219 (22%)
were 7-9 weeks pregnant. Overall, 94.7% (95% confidence interval 93.1% to 96.0%)
reported successfully ending their pregnancy without surgical intervention. Seven
women (0.7%, 0.3% to 1.5%) reported receiving a blood transfusion, and 26 (2.6%,
1.7% to 3.8%) reported receiving antibiotics (route of administration (IV or
oral) could not be determined). No deaths resulting from the intervention were
reported by family, friends, the authorities, or the media. Ninety three women
(9.3%, 7.6% to 11.3%) reported experiencing any symptom for which they were
advised to seek medical advice, and, of these, 87 (95%, 87.8% to 98.2%) sought
attention. None of the five women who did not seek medical attention reported
experiencing an adverse outcome.Conclusions Self sourced medical abortion using
online telemedicine can be highly effective, and outcomes compare favourably with
in clinic protocols. Reported rates of adverse events are low. Women are able to
self identify the symptoms of potentially serious complications, and most report
seeking medical attention when advised. Results have important implications for
women worldwide living in areas where access to abortion is restricted.
PMID- 28512089
TI - Physician age and outcomes in elderly patients in hospital in the US:
observational study.
AB - Objectives To investigate whether outcomes of patients who were admitted to
hospital differ between those treated by younger and older physicians.Design
Observational study.Setting US acute care hospitals.Participants 20% random
sample of Medicare fee-for-service beneficiaries aged >=65 admitted to hospital
with a medical condition in 2011-14 and treated by hospitalist physicians to whom
they were assigned based on scheduled work shifts. To assess the generalizability
of findings, analyses also included patients treated by general internists
including both hospitalists and non-hospitalists.Main outcome measures 30 day
mortality and readmissions and costs of care. Results 736 537 admissions managed
by 18 854 hospitalist physicians (median age 41) were included. Patients'
characteristics were similar across physician ages. After adjustment for
characteristics of patients and physicians and hospital fixed effects
(effectively comparing physicians within the same hospital), patients' adjusted
30 day mortality rates were 10.8% for physicians aged <40 (95% confidence
interval 10.7% to 10.9%), 11.1% for physicians aged 40-49 (11.0% to 11.3%), 11.3%
for physicians aged 50-59 (11.1% to 11.5%), and 12.1% for physicians aged >=60
(11.6% to 12.5%). Among physicians with a high volume of patients, however, there
was no association between physician age and patient mortality. Readmissions did
not vary with physician age, while costs of care were slightly higher among older
physicians. Similar patterns were observed among general internists and in
several sensitivity analyses.Conclusions Within the same hospital, patients
treated by older physicians had higher mortality than patients cared for by
younger physicians, except those physicians treating high volumes of patients.
PMID- 28512090
TI - The Vibrio cholerae VexGH RND Efflux System Maintains Cellular Homeostasis by
Effluxing Vibriobactin.
AB - Resistance-nodulation-division (RND) superfamily efflux systems have been widely
studied for their role in antibiotic resistance, but their native biological
functions remain poorly understood. We previously showed that loss of RND
mediated efflux in Vibrio cholerae resulted in activation of the Cpx two
component regulatory system, which mediates adaptation to stress resulting from
misfolded membrane proteins. Here, we investigated the mechanism linking RND
mediated efflux to the Cpx response. We performed transposon mutagenesis
screening of RND-deficient V. cholerae to identify Cpx suppressors. Suppressor
mutations mapped to genes involved in the biosynthesis of the catechol
siderophore vibriobactin. We subsequently demonstrated that vibriobactin
secretion is impaired in mutants lacking the VexGH RND efflux system and that
impaired vibriobactin secretion is responsible for Cpx system activation,
suggesting that VexGH secretes vibriobactin. This conclusion was bolstered by
results showing that vexGH expression is induced by iron limitation and that vexH
deficient cells exhibit reduced fitness during growth under iron-limiting
conditions. Our results support a model where VexGH contributes to cellular
homeostasis by effluxing vibriobactin. In the absence of vexGH, retained
vibriobactin appears to chelate iron from iron-rich components of the respiratory
chain, with the deferrated proteins functioning to activate the Cpx response. Our
collective results demonstrate that a native function of the V. cholerae VexGH
RND efflux system is in vibriobactin secretion and that vibriobactin efflux is
critical for maintenance of cellular homeostasis.IMPORTANCE RND efflux systems
are ubiquitous Gram-negative transporters that play critical roles in
antimicrobial resistance. In addition to antimicrobial resistance, RND
transporters also affect the expression of diverse phenotypes, including
virulence, cell metabolism, and stress responses. The latter observations suggest
that RND transporters fulfill unknown physiological functions in the cell
independently of their role in antimicrobial resistance. Vibrio cholerae is
representative of many Gram-negative bacteria in encoding multiple RND
transporters that are redundant in antimicrobial resistance and affect multiple
phenotypes. Here we describe a novel function of the V. cholerae VexGH RND
transporter in vibriobactin secretion. We show that vibriobactin production in
VexGH-deficient cells impacts cell homeostasis, leading to activation of the Cpx
stress response and reduced fitness under iron-limiting conditions. Our results
highlight a native physiological function of an RND transporter and provide
insight into the selective forces that maintain what was thought to be a
redundant multidrug transporter.
PMID- 28512092
TI - Quantitative Kinetic Analyses of Shutting Off a Two-Component System.
AB - Cells rely on accurate control of signaling systems to adapt to environmental
perturbations. System deactivation upon stimulus removal is as important as
activation of signaling pathways. The two-component system (TCS) is one of the
major bacterial signaling schemes. In many TCSs, phosphatase activity of the
histidine kinase (HK) is believed to play an essential role in shutting off the
pathway and resetting the system to the prestimulus state. Two basic challenges
are to understand the dynamic behavior of system deactivation and to
quantitatively evaluate the role of phosphatase activity under natural cellular
conditions. Here we report a kinetic analysis of the response to shutting off the
archetype Escherichia coli PhoR-PhoB TCS pathway using both transcription
reporter assays and in vivo phosphorylation analyses. Upon removal of the
stimulus, the pathway is shut off by rapid dephosphorylation of the PhoB response
regulator (RR) while PhoB-regulated gene products gradually reset to prestimulus
levels through growth dilution. We developed an approach combining
experimentation and modeling to assess in vivo kinetic parameters of the
phosphatase activity with kinetic data from multiple phosphatase-diminished
mutants. This enabled an estimation of the PhoR phosphatase activity in vivo,
which is much stronger than the phosphatase activity of PhoR cytoplasmic domains
analyzed in vitro We quantitatively modeled how strong the phosphatase activity
needs to be to suppress nonspecific phosphorylation in TCSs and discovered that
strong phosphatase activity of PhoR is required for cross-phosphorylation
suppression.IMPORTANCE Activation of TCSs has been extensively studied; however,
the kinetics of shutting off TCS pathways is not well characterized. We present
comprehensive analyses of the shutoff response for the PhoR-PhoB system that
reveal the impact of phosphatase activity on shutoff kinetics. This allows
development of a quantitative framework not only to characterize the phosphatase
activity in the natural cellular environment but also to understand the
requirement for specific strengths of phosphatase activity to suppress
nonspecific phosphorylation. Our model suggests that the ratio of the phosphatase
rate to the nonspecific phosphorylation rate correlates with TCS expression
levels and the ratio of the RR to HK, which may contribute to the great diversity
of enzyme levels and activities observed in different TCSs.
PMID- 28512091
TI - Conformational Flexibility in the Immunoglobulin-Like Domain of the Hepatitis C
Virus Glycoprotein E2.
AB - The hepatitis C virus (HCV) glycoprotein E2 is the major target of neutralizing
antibodies and is therefore highly relevant for vaccine design. Its structure
features a central immunoglobulin (Ig)-like beta-sandwich that contributes to the
binding site for the cellular receptor CD81. We show that a synthetic peptide
corresponding to a beta-strand of this Ig-like domain forms an alpha-helix in
complex with the anti-E2 antibody DAO5, demonstrating an inside-out flip of
hydrophobic residues and a secondary structure change in the composite CD81
binding site. A detailed interaction analysis of DAO5 and cross-competing
neutralizing antibodies with soluble E2 revealed that the Ig-like domain is
trapped by different antibodies in at least two distinct conformations. DAO5
specifically captures retrovirus particles bearing HCV glycoproteins (HCVpp) and
infectious cell culture-derived HCV particles (HCVcc). Infection of cells by DAO5
captured HCVpp can be blocked by a cross-competing neutralizing antibody,
indicating that a single virus particle simultaneously displays E2 molecules in
more than one conformation on its surface. Such conformational plasticity of the
HCV E2 receptor binding site has important implications for immunogen
design.IMPORTANCE Recent advances in the treatment of hepatitis C virus (HCV)
infection with direct-acting antiviral drugs have enabled the control of this
major human pathogen. However, due to their high costs and limited accessibility
in combination with the lack of awareness of the mostly asymptomatic infection,
there is an unchanged urgent need for an effective vaccine. The viral
glycoprotein E2 contains regions that are crucial for virus entry into the host
cell, and antibodies that bind to these regions can neutralize infection. One of
the major targets of neutralizing antibodies is the central immunoglobulin (Ig)
like domain within E2. We show here that this Ig-like domain is conformationally
flexible at the surface of infectious HCV particles and pseudoparticles. Our
study provides novel insights into the interactions of HCV E2 with the humoral
immune system that should aid future vaccine development.
PMID- 28512094
TI - Intrinsic Toxin-Derived Peptides Destabilize and Inactivate Clostridium difficile
TcdB.
AB - Clostridium difficile infection (CDI) is a major cause of hospital-associated,
antibiotic-induced diarrhea, which is largely mediated by the production of two
large multidomain clostridial toxins, TcdA and TcdB. Both toxins coordinate the
action of specific domains to bind receptors, enter cells, and deliver a
catalytic fragment into the cytosol. This results in GTPase inactivation, actin
disassembly, and cytotoxicity. TcdB in particular has been shown to encode a
region covering amino acids 1753 to 1851 that affects epitope exposure and
cytotoxicity. Surprisingly, studies here show that several peptides derived from
this region, which share the consensus sequence 1769NVFKGNTISDK1779, protect
cells from the action of TcdB. One peptide, PepB2, forms multiple interactions
with the carboxy-terminal region of TcdB, destabilizes TcdB structure, and
disrupts cell binding. We further show that these effects require PepB2 to form a
higher-order polymeric complex, a process that requires the central GN amino acid
pair. These data suggest that TcdB1769-1779 interacts with repeat sequences in
the proximal carboxy-terminal domain of TcdB (i.e., the CROP domain) to alter the
conformation of TcdB. Furthermore, these studies provide insights into TcdB
structure and functions that can be exploited to inactivate this critical
virulence factor and ameliorate the course of CDI.IMPORTANCEClostridium difficile
is a leading cause of hospital-associated illness that is often associated with
antibiotic treatment. To cause disease, C. difficile secretes toxins, including
TcdB, which is a multidomain intracellular bacterial toxin that undergoes
conformational changes during cellular intoxication. This study describes the
development of peptide-based inhibitors that target a region of TcdB thought to
be critical for structural integrity of the toxin. The results show that peptides
derived from a structurally important region of TcdB can be used to destabilize
the toxin and prevent cellular intoxication. Importantly, this work provides a
novel means of toxin inhibition that could in the future develop into a C.
difficile treatment.
PMID- 28512096
TI - Erratum for Briese et al., "Virome Capture Sequencing Enables Sensitive Viral
Diagnosis and Comprehensive Virome Analysis".
PMID- 28512093
TI - Population Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing
Klebsiella pneumoniae Isolates, Houston, Texas: Unexpected Abundance of Clonal
Group 307.
AB - Klebsiella pneumoniae is a major human pathogen responsible for high morbidity
and mortality rates. The emergence and spread of strains resistant to multiple
antimicrobial agents and documented large nosocomial outbreaks are especially
concerning. To develop new therapeutic strategies for K. pneumoniae, it is
imperative to understand the population genomic structure of strains causing
human infections. To address this knowledge gap, we sequenced the genomes of
1,777 extended-spectrum beta-lactamase-producing K. pneumoniae strains cultured
from patients in the 2,000-bed Houston Methodist Hospital system between
September 2011 and May 2015, representing a comprehensive, population-based
strain sample. Strains of largely uncharacterized clonal group 307 (CG307) caused
more infections than those of well-studied epidemic CG258. Strains varied
markedly in gene content and had an extensive array of small and very large
plasmids, often containing antimicrobial resistance genes. Some patients with
multiple strains cultured over time were infected with genetically distinct
clones. We identified 15 strains expressing the New Delhi metallo-beta-lactamase
1 (NDM-1) enzyme that confers broad resistance to nearly all beta-lactam
antibiotics. Transcriptome sequencing analysis of 10 phylogenetically diverse
strains showed that the global transcriptome of each strain was unique and highly
variable. Experimental mouse infection provided new information about
immunological parameters of host-pathogen interaction. We exploited the large
data set to develop whole-genome sequence-based classifiers that accurately
predict clinical antimicrobial resistance for 12 of the 16 antibiotics tested. We
conclude that analysis of large, comprehensive, population-based strain samples
can assist understanding of the molecular diversity of these organisms and
contribute to enhanced translational research.IMPORTANCEKlebsiella pneumoniae
causes human infections that are increasingly difficult to treat because many
strains are resistant to multiple antibiotics. Clonal group 258 (CG258) organisms
have caused outbreaks in health care settings worldwide. Using a comprehensive
population-based sample of extended-spectrum beta-lactamase (ESBL)-producing K.
pneumoniae strains, we show that a relatively uncommon clonal type, CG307, caused
the plurality of ESBL-producing K. pneumoniae infections in our patients. We
discovered that CG307 strains have been abundant in Houston for many years. As
assessed by experimental mouse infection, CG307 strains were as virulent as
pandemic CG258 strains. Our results may portend the emergence of an especially
successful clonal group of antibiotic-resistant K. pneumoniae.
PMID- 28512095
TI - Structure-Based Mutations in the Herpes Simplex Virus 1 Glycoprotein B Ectodomain
Arm Impart a Slow-Entry Phenotype.
AB - Glycoprotein B (gB) is the conserved herpesvirus fusion protein, and it is
required for the entry of herpesviruses. The structure of the postfusion
conformation of gB has been solved for several herpesviruses; however, the gB
prefusion crystal structure and the details of how the protein refolds from a
prefusion to a postfusion form to mediate fusion have not been determined. Using
structure-based mutagenesis, we previously reported that three mutations (I671A,
H681A, and F683A) in the C-terminal arm of the gB ectodomain greatly reduced cell
cell fusion. This fusion deficit could be rescued by the addition of a
hyperfusogenic mutation, suggesting that the gB triple mutant was not misfolded.
Using a bacterial artificial chromosome (BAC), we constructed two independent
herpes simplex virus 1 mutant strains (gB 3A) carrying the three arm mutations.
The gB 3A viruses have 200-fold smaller plaques than the wild-type virus and
demonstrate remarkably delayed entry into cells. Single-step and multistep growth
curves show that gB 3A viruses have delayed replication kinetics. Interestingly,
incubation at 40 degrees C promoted the entry of the gB 3A viruses. We propose
that the gB 3A viruses' entry deficit is due to a loss of interactions between
residues in the gB C-terminal arm and the coiled-coil core of gB. The results
suggest that the triple alanine mutation may destabilize the postfusion gB
conformation and/or stabilize the prefusion gB conformation and that exposure to
elevated temperatures can overcome the defect in gB 3A viruses.IMPORTANCE Because
of its complexity, the mechanism of herpesvirus entry into cells is not well
understood. Our study investigated one of the most important unanswered questions
about herpesvirus entry; i.e., how does the herpesvirus fusion protein gB mediate
membrane fusion? gB is an essential protein that is conserved in all
herpesviruses and is thought to undergo a conformational change to provide the
energy to fuse the viral and cellular membranes. Using our understanding of the
structure of gB, we designed mutations in the gB "arm" region that we predicted
would impede gB function. We introduced these mutations into herpes simplex virus
1 by using a bacterial artificial chromosome, and the mutant virus exhibited a
drastically delayed rate of entry. This entry defect was rescued by incubation at
elevated temperatures, supporting a hypothesis that the engineered mutations
altered the energetics of gB refolding. This study supports our hypothesis that
an interaction between the gB arm and the core of gB is critical for gB refolding
and the execution of membrane fusion, thus providing key details about the
function of gB in herpesvirus-mediated fusion and subsequent virus entry.
PMID- 28512098
TI - A rare case of thrombotic microangiopathy triggered by acute pancreatitis.
AB - Thrombotic microangiopathy (TMA) occurring after acute pancreatitis is rarely
described. Without prompt intervention, TMA can be, and often is, lethal, so
prompt recognition is important. Here, we present a case of a 61-year-old woman
with a history of alcohol misuse who presented with epigastric pain, nausea and
vomiting after binge drinking. Elevated serum lipase and imaging were suggestive
of acute-on-chronic pancreatitis. Although the patient's symptoms of acute
pancreatitis subsided, her anaemia, thrombocytopenia and acute kidney injury
worsened. A peripheral blood smear revealed schistocytes, prompting suspicion for
TMA. Therapeutic plasma exchange (TPE) was promptly initiated and she completed
10 TPE sessions that improved her anaemia and serum creatinine and resolved the
thrombocytopenia. Since TPE was effective and the ADAMTS13 assay revealed 55%
activity in the absence of anti-ADAMTS13 IgG prior to initiation of therapy, a
confident diagnosis of TMA caused by acute pancreatitis was made. There was no
evidence of relapse 2 years later.
PMID- 28512097
TI - Glutathionylation of Yersinia pestis LcrV and Its Effects on Plague Pathogenesis.
AB - Glutathionylation, the formation of reversible mixed disulfides between
glutathione and protein cysteine residues, is a posttranslational modification
previously observed for intracellular proteins of bacteria. Here we show that
Yersinia pestis LcrV, a secreted protein capping the type III secretion machine,
is glutathionylated at Cys273 and that this modification promotes association
with host ribosomal protein S3 (RPS3), moderates Y. pestis type III effector
transport and killing of macrophages, and enhances bubonic plague pathogenesis in
mice and rats. Secreted LcrV was purified and analyzed by mass spectrometry to
reveal glutathionylation, a modification that is abolished by the codon
substitution Cys273Ala in lcrV Moreover, the lcrVC273A mutation enhanced the
survival of animals in models of bubonic plague. Investigating the molecular
mechanism responsible for these virulence attributes, we identified macrophage
RPS3 as a ligand of LcrV, an association that is perturbed by the Cys273Ala
substitution. Furthermore, macrophages infected by the lcrVC273A variant
displayed accelerated apoptotic death and diminished proinflammatory cytokine
release. Deletion of gshB, which encodes glutathione synthetase of Y. pestis,
resulted in undetectable levels of intracellular glutathione, and we used a Y.
pestis DeltagshB mutant to characterize the biochemical pathway of LcrV
glutathionylation, establishing that LcrV is modified after its transport to the
type III needle via disulfide bond formation with extracellular oxidized
glutathione.IMPORTANCEYersinia pestis, the causative agent of plague, has killed
large segments of the human population; however, the molecular bases for the
extraordinary virulence attributes of this pathogen are not well understood. We
show here that LcrV, the cap protein of bacterial type III secretion needles, is
modified by host glutathione and that this modification contributes to the high
virulence of Y. pestis in mouse and rat models for bubonic plague. These data
suggest that Y. pestis exploits glutathione in host tissues to activate a
virulence strategy, thereby accelerating plague pathogenesis.
PMID- 28512099
TI - Mitral valve vegetation diagnosed with oesophageal ultrasound with bronchoscope
(EUS-B).
AB - Oesophageal ultrasound with bronchoscope (EUS-B) is designed to evaluate
mediastinal structures. We describe a case of a 78-year-old woman who presented
with altered mental status for 2 weeks. CT head revealed a subacute infarct in
the right middle cerebral artery distribution. She was also found to have a lung
mass on chest imaging. EUS-B-guided fine needle aspiration demonstrated the
presence of adenocarcinoma in station 7 lymph node and in the mass.
Immunohistochemistry confirmed it to be a lung primary as the Thyroid
Transcription Factor-1 (TTF-1) was strongly positive. During the procedure, the
cardiac valves were evaluated, and a mitral valve vegetation was noted. Formal
echocardiography confirmed the presence of the vegetation. During hospital stay,
the patient developed fever. Her blood cultures grew oxacillin-resistant
Staphylococcus aureus. She was subsequently treated for infective endocarditis.
We suggest that the use of EUS-B to routinely scan adjacent structures during a
procedure may help obtain additional clinical information that may be critical to
patient management.
PMID- 28512100
TI - Anaemia and respiratory failure in a child: can it be idiopathic pulmonary
haemosiderosis?
AB - We present an 8-year-old male child admitted with cough and high-grade fever for
7 days and respiratory difficulty for 2 days. There was a history of blood
transfusion at 2 years of age during a respiratory illness. The child was
anaemic, tachycardic, tachypnoeic and hypoxic at presentation. Chest examination
revealed equal air entry with fine crackles bilaterally. Blood reports were
suggestive of anaemia (haemoglobin 6.5 g/dL), leucocytosis and high C reactive
protein levels. Chest radiograph revealed bilateral air space opacities involving
diffuse lung fields, right more than left. Relevant microbiological workup was
negative. Based on the clinical scenario and investigations, a provisional
diagnosis of pulmonary haemosiderosis was kept. The patient was started on
intravenous pulse methylprednisolone. Fibre-optic bronchoscopy was done following
recovery from the acute event. Bronchoalveolar lavage demonstrated a significant
number of haemosiderin-laden macrophages confirming pulmonary haemosiderosis.
PMID- 28512101
TI - Novel use of combination of electromyography and ultrasound to guide quadratus
lumborum block after open appendicectomy.
AB - The quadratus lumborum (QL) block facilitates the administration of anaesthesia
to the anterior abdominal wall. The use of ultrasound (US) improves the accuracy
of the QL block and reduces the risk of adverse events. Electromyography (EMG) in
combination with US for muscle plane blocks has not been described previously. We
postulated that the addition of EMG-guided needle positioning might assist the
execution of this block. This case report describes the first use of combined
needle EMG and US to carry out a QL block performed for postoperative analgesia
following an open appendicectomy.
PMID- 28512102
TI - Uncommon presentation of adult-form scimitar syndrome associated with single left
pulmonary vein in a pregnant woman.
AB - Scimitar syndrome is the constellation of malformations including an abnormal
venous drainage of the right lung into the inferior vena cava, associated with
the right lung and systemic supply to the right lung. The anomalous vein looks
like the curved, Turkish sword (scimitar), hence the name.The adult form of
scimitar syndrome is rare, and it is usually an incidental diagnosis based on the
characteristic finding on radiological imaging since the patients are usually
asymptomatic or with minimal symptoms.Our patient presented with a rare
presentation of scimitar syndrome, which is tachyarrhythmia (sinus tachycardia,
with episodes of supraventricular tachycardia). The diagnosis of scimitar
syndrome was made based on the typical radiological finding of the anomalous
venous drainage on CT angiography. Our patient does not have the full spectrum of
the scimitar syndrome; therefore, she did not suffer from the usual complication
(pulmonary hypertension). She was treated with ablation without surgical
intervention.
PMID- 28512103
TI - Pericardial incidentaloma: benign pericardial cyst.
PMID- 28512104
TI - Mitral Stenosis.
PMID- 28512106
TI - David Oliver: The NHS's understaffing is its Achilles' heel.
PMID- 28512105
TI - Double hit lymphoma presenting as haemophagocytic lymphohistiocytosis.
PMID- 28512107
TI - Divergent Requirements for EZH1 in Heart Development Versus Regeneration.
AB - RATIONALE: Polycomb repressive complex 2 is a major epigenetic repressor that
deposits methylation on histone H3 on lysine 27 (H3K27me) and controls
differentiation and function of many cells, including cardiac myocytes. EZH1 and
EZH2 are 2 alternative catalytic subunits with partial functional redundancy. The
relative roles of EZH1 and EZH2 in heart development and regeneration are
unknown. OBJECTIVE: We compared the roles of EZH1 versus EZH2 in heart
development and neonatal heart regeneration. METHODS AND RESULTS: Heart
development was normal in Ezh1-/- (Ezh1 knockout) and Ezh2f/f::cTNT-Cre (Ezh2
knockout) embryos. Ablation of both genes in Ezh1-/-::Ezh2f/f::cTNT-Cre embryos
caused lethal heart malformations, including hypertrabeculation, compact
myocardial hypoplasia, and ventricular septal defect. Epigenome and transcriptome
profiling showed that derepressed genes were upregulated in a manner consistent
with total EZH dose. In neonatal heart regeneration, Ezh1 was required, but Ezh2
was dispensable. This finding was further supported by rescue experiments:
cardiac myocyte-restricted re-expression of EZH1 but not EZH2 restored neonatal
heart regeneration in Ezh1 knockout. In myocardial infarction performed outside
of the neonatal regenerative window, EZH1 but not EZH2 likewise improved heart
function and stimulated cardiac myocyte proliferation. Mechanistically, EZH1
occupied and activated genes related to cardiac growth. CONCLUSIONS: Our work
unravels divergent mechanisms of EZH1 in heart development and regeneration,
which will empower efforts to overcome epigenetic barriers to heart regeneration.
PMID- 28512110
TI - In patients with intracerebral haemorrhage and concomitant atrial fibrillation,
optimal timing of reinitiating anticoagulants may be 7-8 weeks after ICH.
PMID- 28512109
TI - Resumption of anticoagulation after major bleeding decreases the risk of stroke
in patients with atrial fibrillation.
PMID- 28512108
TI - Clinical Relevance and Role of Neuronal AT1 Receptors in ADAM17-Mediated ACE2
Shedding in Neurogenic Hypertension.
AB - RATIONALE: Neurogenic hypertension is characterized by an increase in sympathetic
activity and often resistance to drug treatments. We previously reported that it
is also associated with a reduction of angiotensin-converting enzyme type 2
(ACE2) and an increase in a disintegrin and metalloprotease 17 (ADAM17) activity
in experimental hypertension. In addition, while multiple cells within the
central nervous system have been involved in the development of neurogenic
hypertension, the contribution of ADAM17 has not been investigated. OBJECTIVE: To
assess the clinical relevance of this ADAM17-mediated ACE2 shedding in
hypertensive patients and further identify the cell types and signaling pathways
involved in this process. METHODS AND RESULTS: Using a mass spectrometry-based
assay, we identified ACE2 as the main enzyme converting angiotensin II into
angiotensin-(1-7) in human cerebrospinal fluid. We also observed an increase in
ACE2 activity in the cerebrospinal fluid of hypertensive patients, which was
correlated with systolic blood pressure. Moreover, the increased level of tumor
necrosis factor-alpha in those cerebrospinal fluid samples confirmed that ADAM17
was upregulated in the brain of hypertensive patients. To further assess the
interaction between brain renin-angiotensin system and ADAM17, we generated mice
lacking angiotensin II type 1 receptors specifically on neurons. Our data reveal
that despite expression on astrocytes and other cells types in the brain, ADAM17
upregulation during deoxycorticosterone acetate-salt hypertension occurs
selectively on neurons, and neuronal angiotensin II type 1 receptors are
indispensable to this process. Mechanistically, reactive oxygen species and
extracellular signal-regulated kinase were found to mediate ADAM17 activation.
CONCLUSIONS: Our data demonstrate that angiotensin II type 1 receptors promote
ADAM17-mediated ACE2 shedding in the brain of hypertensive patients, leading to a
loss in compensatory activity during neurogenic hypertension.
PMID- 28512111
TI - An Initial Evaluation of the Impact of Pokemon GO on Physical Activity.
AB - BACKGROUND: Pokemon GO is a location-based augmented reality game. Using GPS and
the camera on a smartphone, the game requires players to travel in real world to
capture animated creatures, called Pokemon. We examined the impact of Pokemon GO
on physical activity (PA). METHODS AND RESULTS: A pre-post observational study of
167 Pokemon GO players who were self-enrolled through recruitment flyers or
online social media was performed. Participants were instructed to provide
screenshots of their step counts recorded by the iPhone Health app between June
15 and July 31, 2016, which was 3 weeks before and 3 weeks after the Pokemon GO
release date. Of 167 participants, the median age was 25 years (interquartile
range, 21-29 years). The daily average steps of participants at baseline was 5678
(SD, 2833; median, 5718 [interquartile range, 3675-7279]). After initiation of
Pokemon GO, daily activity rose to 7654 steps (SD, 3616; median, 7232
[interquartile range, 5041-9744], pre-post change: 1976; 95% CI, 1494-2458, or a
34.8% relative increase [P<0.001]). On average, 10 000 "XP" points (a measure of
game progression) was associated with 2134 additional steps per day (95% CI, 1673
2595), suggesting a potential dose-response relationship. The number of
participants achieving a goal of 10 000+ steps per day increased from 15.3%
before to 27.5% after (odds ratio, 2.06; 95% CI, 1.70-2.50). Increased PA was
also observed in subgroups, with the largest increases seen in participants who
spent more time playing Pokemon GO, those who were overweight/obese, or those
with a lower baseline PA level. CONCLUSIONS: Pokemon GO participation was
associated with a significant increase in PA among young adults. Incorporating PA
into gameplay may provide an alternative way to promote PA in persons who are
attracted to the game. CLINICAL TRIAL REGISTRATION: URL:
http://www.clinicaltrials.gov. Unique identifier: NCT02888314.
PMID- 28512113
TI - How Symptomatic Should a Hypertrophic Obstructive Cardiomyopathy Patient Be to
Consider Alcohol Septal Ablation?
PMID- 28512112
TI - Outcome of Alcohol Septal Ablation in Mildly Symptomatic Patients With
Hypertrophic Obstructive Cardiomyopathy: A Long-Term Follow-Up Study Based on the
Euro-Alcohol Septal Ablation Registry.
AB - BACKGROUND: The long-term efficacy and safety of alcohol septal ablation (ASA) in
patients with highly symptomatic hypertrophic obstructive cardiomyopathy has been
demonstrated. The aim of this study was to evaluate the long-term outcomes of
mildly symptomatic patients with hypertrophic obstructive cardiomyopathy treated
with ASA. METHODS AND RESULTS: We retrospectively evaluated consecutive patients
enrolled in the Euro-ASA registry (1427 patients) and identified 161 patients
(53+/-13 years; 27% women) who were mildly symptomatic (New York Heart
Association [NYHA] class II) pre-ASA. The median (interquartile range) follow-up
was 4.8 (1.7-8.5) years. The clinical outcome was assessed and compared with the
age- and sex-matched general population. The 30-day mortality after ASA was 0.6%
and the annual all-cause mortality rate was 1.7%, which was similar to the age-
and sex-matched general population (P=0.62). A total of 141 (88%) patients had
resting left ventricular outflow tract gradient at the last clinical checkup <=30
mm Hg. Obstruction was reduced from 63+/-32 to 15+/-19 mm Hg (P<0.01), and the
mean NYHA class decreased from 2.0+/-0 to 1.3+/-0.1 (P<0.01); 69%, 29%, and 2% of
patients were in NYHA class I, II, and III at the last clinical checkup,
respectively. CONCLUSIONS: Mildly symptomatic hypertrophic obstructive
cardiomyopathy patients treated with ASA had sustained symptomatic and
hemodynamic relief with a low risk of developing severe heart failure. Their
survival is comparable to the general population.
PMID- 28512115
TI - Endogenous Hydrogen Sulfide Enhances Carotid Sinus Baroreceptor Sensitivity by
Activating the Transient Receptor Potential Cation Channel Subfamily V Member 1
(TRPV1) Channel.
AB - BACKGROUND: We aimed to investigate the regulatory effects of hydrogen sulfide
(H2S) on carotid sinus baroreceptor sensitivity and its mechanisms. METHODS AND
RESULTS: Male Wistar-Kyoto rats and spontaneously hypertensive rats (SHRs) were
used in the experiment and were given an H2S donor or a cystathionine-beta
synthase inhibitor, hydroxylamine, for 8 weeks. Systolic blood pressure and the
cystathionine-beta-synthase/H2S pathway in carotid sinus were detected. Carotid
sinus baroreceptor sensitivity and the functional curve of the carotid
baroreceptor were analyzed using the isolated carotid sinus perfusion technique.
Effects of H2S on transient receptor potential cation channel subfamily V member
1 (TRPV1) expression and S-sulfhydration were detected. In SHRs, systolic blood
pressure was markedly increased, but the cystathionine-beta-synthase/H2S pathway
in the carotid sinus was downregulated in comparison to that of Wistar-Kyoto
rats. Carotid sinus baroreceptor sensitivity in SHRs was reduced, demonstrated by
the right and upward shift of the functional curve of the carotid baroreceptor.
Meanwhile, the downregulation of TRPV1 protein was demonstrated in the carotid
sinus; however, H2S reduced systolic blood pressure but enhanced carotid sinus
baroreceptor sensitivity in SHRs, along with TRPV1 upregulation in the carotid
sinus. In contrast, hydroxylamine significantly increased the systolic blood
pressure of Wistar-Kyoto rats, along with decreased carotid sinus baroreceptor
sensitivity and reduced TRPV1 protein expression in the carotid sinus.
Furthermore, H2S-induced enhancement of carotid sinus baroreceptor sensitivity of
SHRs could be amplified by capsaicin but reduced by capsazepine. Moreover, H2S
facilitated S-sulfhydration of TRPV1 protein in the carotid sinus of SHRs and
Wistar-Kyoto rats. CONCLUSIONS: H2S regulated blood pressure via an increase in
TRPV1 protein expression and its activity to enhance carotid sinus baroreceptor
sensitivity.
PMID- 28512114
TI - Associations of Acid Suppressive Therapy With Cardiac Mortality in Heart Failure
Patients.
AB - BACKGROUND: It has been recently reported that histamine H2 receptor antagonists
(H2RAs) are associated with impairment of ventricular remodeling and incident
heart failure. In addition, favorable pleiotropic effects and adverse effects of
proton pump inhibitors (PPIs) on cardiovascular disease have also been reported.
We examined the associations of acid suppressive therapy using H2RAs or PPIs with
cardiac mortality in patients with heart failure. METHODS AND RESULTS: In total,
1191 consecutive heart failure patients were divided into 3 groups: a non-acid
suppressive therapy group (n=363), an H2RA group (n=164), and a PPI group
(n=664). In the follow-up period (mean 995 days), 169 cardiac deaths occurred. In
the Kaplan-Meier analysis, cardiac mortality was significantly lower in the PPI
group than in the H2RA and non-acid suppressive therapy groups (11.0% versus
21.3% and 16.8%, respectively; log-rank P=0.004). In the multivariable Cox
proportional hazards analysis, use of PPIs, but not H2RAs, was found to be an
independent predictor of cardiac mortality (PPIs: hazard ratio 0.488, P=0.002;
H2RAs: hazard ratio 0.855, P=0.579). The propensity-matched 1:1 cohort was
assessed based on propensity score (H2RAs, n=164; PPIs, n=164). Cardiac mortality
was significantly lower in the PPI group than in the H2RA group in the
postmatched cohort (log-rank P=0.025). In the Cox proportional hazards analysis,
the use of PPIs was a predictor of cardiac mortality in the postmatched cohort
(hazard ratio 0.528, P=0.028). CONCLUSIONS: PPIs may be associated with better
outcome in patients with heart failure.
PMID- 28512116
TI - Weekday and Survival After Cardiac Surgery-A Swedish Nationwide Cohort Study in
106 473 Patients.
AB - BACKGROUND: The purpose of this study was to investigate the association between
weekday of surgery and survival following cardiac surgery. METHODS AND RESULTS:
In a nationwide cohort study, we included all patients who underwent cardiac
surgery in 1999-2013 from the SWEDEHEART (Swedish Web-system for Enhancement and
Development of Evidence-based care in Heart disease Evaluated According to
Recommended Therapies) register. All-cause mortality until March 2014 was
obtained from national registers. The association between weekday of surgery and
mortality was estimated using Cox regression, and reported as hazard ratios with
95% CI. We used the restricted mean survival time difference to estimate loss of
life related to weekday of surgery. Among 106 473 patients, 25 221 (24%), 24 471
(23%), 22 977 (22%), 20 189 (19%), 9251 (8.7%), and 4364 (4.1%) underwent surgery
during a Monday, Tuesday, Wednesday, Thursday, Friday, and a Saturday/Sunday,
respectively. More patients were operated on urgently during Friday to Sunday,
and unadjusted analyses showed higher early and late mortality in those patients.
The adjusted hazard ratios (95% CI) were 1.00 (0.89-1.13), 1.00 (0.88-1.12), 1.02
(0.90-1.16), 1.17 (1.01-1.37), and 1.05 (0.86-1.29) in patients who underwent
surgery during a Tuesday, Wednesday, Thursday, Friday, and Saturday/Sunday
compared to a Monday, after 1 year of follow-up conditional on 30-day survival.
In elective surgery (n=46 146), the 1-year restricted mean survival time
difference (95% CI) was -0.5 (-1.8-0.8), -0.5 (-1.9-0.8), -1.0 (-2.6-0.5), 0.02 (
2.2-2.3), and -1.2 (-6.3-3.9) days in patients who underwent surgery during a
Tuesday, Wednesday, Thursday, Friday, and a Saturday/Sunday, respectively,
compared to a Monday. CONCLUSIONS: We found no evidence of a clinically relevant
weekday effect in patents who underwent cardiac surgery in Sweden during a 15
year period. These data suggest that the early risk and long-term prognosis
following cardiac surgery was not affected by the weekday of surgery. CLINICAL
TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier:
NCT02276950.
PMID- 28512117
TI - The interaction of MC3R and MC4R with MRAP2, ACTH, alpha-MSH and AgRP in
chickens.
AB - The interaction of melanocortin-4 (MC4R) and melanocortin-3 (MC3R) receptors with
proopiomelanocortin (POMC)-derived peptides (e.g. alpha-MSH), agouti-related
protein (AgRP) and melanocortin-2 receptor accessory protein 2 (MRAP2) is
suggested to play critical roles in energy balance of vertebrates. However,
evidence on their interaction in birds remains scarce. Our study aims to reveal
their interaction in chickens and the results showed that (1) chicken (c-)MC3R
and cMC4R expressed in Chinese hamster ovary (CHO) cells can be activated by
alpha-MSH and ACTH1-39 equipotently, monitored by a pGL3-CRE-luciferase reporter
system; (2) cMC3R and cMC4R, when co-expressed with cMRAP2 (or cMRAP, a cMRAP2
homolog), show increased sensitivity to ACTH treatment and thus likely act as
ACTH-preferring receptors, and the interaction between cMC3R/cMC4R and cMRAP2 was
demonstrated by co-immunoprecipitation assay; (3) both cMC3R and cMC4R display
constitutive activity when expressed in CHO cells, as monitored by dual
luciferase reporter assay, and cMRAP2 (and cMRAP) can modulate their constitutive
activity; (4) AgRP inhibits the constitutive activity of cMC3R/cMC4R, and it also
antagonizes ACTH/alpha-MSH action on cMC4R/cMC3R, indicating that AgRP functions
as the inverse agonist and antagonist for both receptors. These findings,
together with the co-expression of cMC4R, cMC3R, cMRAP2, cAgRP and cPOMC in
chicken hypothalamus detected by quantitative real-time PCR, suggest that within
the hypothalamus, alpha-MSH/ACTH, AgRP and MRAP2 may interact at the MC4R(/MC3R)
interface to control energy balance. Furthermore, our data provide novel proof
for the involvement of MRAP2 (and MRAP) in fine-tuning the constitutive activity
and ligand sensitivity and selectivity of both MC3R and MC4R in vertebrates.
PMID- 28512119
TI - Complementary and integrative medicine in the management of headache.
AB - Headaches, including primary headaches such as migraine and tension-type
headache, are a common clinical problem. Complementary and integrative medicine
(CIM), formerly known as complementary and alternative medicine (CAM), uses
evidence informed modalities to assist in the health and healing of patients. CIM
commonly includes the use of nutrition, movement practices, manual therapy,
traditional Chinese medicine, and mind-body strategies. This review summarizes
the literature on the use of CIM for primary headache and is based on five meta
analyses, seven systematic reviews, and 34 randomized controlled trials (RCTs).
The overall quality of the evidence for CIM in headache management is generally
low and occasionally moderate. Available evidence suggests that traditional
Chinese medicine including acupuncture, massage, yoga, biofeedback, and
meditation have a positive effect on migraine and tension headaches. Spinal
manipulation, chiropractic care, some supplements and botanicals, diet
alteration, and hydrotherapy may also be beneficial in migraine headache. CIM has
not been studied or it is not effective for cluster headache. Further research is
needed to determine the most effective role for CIM in patients with headache.
PMID- 28512118
TI - Epstein-Barr virus-encoded LMP2A stimulates migration of nasopharyngeal carcinoma
cells via the EGFR/Ca2+/calpain/ITGbeta4 axis.
AB - Epstein-Barr virus (EBV)-encoded latent membrane protein 2A (LMP2A) promotes the
motility of nasopharyngeal carcinoma (NPC) cells. Previously, we have shown that
the localization of integrin beta4 (ITGbeta4) is regulated by LMP2A, with
ITGbeta4 concentrated at the cellular protrusions in LMP2A-expressing NPC cells.
In the present study, we aim to further investigate mechanisms involved in this
process and its contribution to cell motility. We show that expression of LMP2A
was correlated with increased epidermal growth factor receptor (EGFR) activation,
elevated levels of intracellular Ca2+, calpain activation and accelerated
cleavage of ITGbeta4. Activation of EGFR and calpain activity was responsible for
a redistribution of ITGbeta4 from the basal layer of NPC cells to peripheral
membrane structures, which correlated with an increased migratory capacity of NPC
cells. Furthermore, we demonstrated that the calpain inhibitor calpastatin was
downregulated in NPC primary tumors. In conclusion, our results point to LMP2A
mediated targeting of the EGFR/Ca2+/calpain/ITGbeta4 signaling system as a
mechanism underlying the increased motility of NPC cells. We suggest that calpain
facilitated cleavage of ITGbeta4 contributes to the malignant phenotype of NPC
cells.
PMID- 28512120
TI - Serum Albumin and Disease Severity of Non-Cystic Fibrosis Bronchiectasis.
AB - BACKGROUND: A clinical classification system has been developed to define the
severity and predict the prognosis of subjects with non-cystic fibrosis (CF)
bronchiectasis. We aimed to identify laboratory parameters that are correlated
with the bronchiectasis severity index (BSI) and FACED score. METHODS: The
medical records of 107 subjects with non-CF bronchiectasis for whom BSI and FACED
scores could be calculated were retrospectively reviewed. The correlations
between the laboratory parameters and BSI or FACED score were assessed, and
multiple-linear regression analysis was performed to identify variables
independently associated with BSI and FACED score. An additional subgroup
analysis was performed according to sex. RESULTS: Among all of the enrolled
subjects, 49 (45.8%) were male and 58 (54.2%) were female. The mean BSI and FACED
scores were 9.43 +/- 3.81 and 1.92 +/- 1.59, respectively. The serum albumin
level (r = -0.49), bilirubin level (r = -0.31), C-reactive protein level (r =
0.22), hemoglobin level (r = -0.2), and platelet/lymphocyte ratio (r = 0.31) were
significantly correlated with BSI. Meanwhile, serum albumin (r = -0.37) and
bilirubin level (r = -0.25) showed a significant correlation with the FACED
score. Multiple-linear regression analysis showed that the serum bilirubin level
was independently associated with BSI, and the serum albumin level was
independently associated with both scoring systems. Subgroup analysis revealed
that the level of uric acid was also a significant variable independently
associated with the BSI in male bronchiectasis subjects. CONCLUSIONS: Several
laboratory variables were identified as possible prognostic factors for non-CF
bronchiectasis. Among them, the serum albumin level exhibited the strongest
correlation and was identified as an independent variable associated with the BSI
and FACED scores.
PMID- 28512122
TI - Labour calls for inquiry into NHS cyber-attack.
PMID- 28512121
TI - Agricultural pest control with CRISPR-based gene drive: time for public debate:
Should we use gene drive for pest control?
PMID- 28512123
TI - Treatment of severe hypocalcaemia due to osteoblastic metastases in a patient
with post-thyroidectomy hypoparathyroidism with 153Sm-EDTMP.
AB - Symptomatic hypocalcaemia is an uncommon finding in patients with malignant
tumours. We describe a patient with advanced metastatic breast cancer who
developed severe hypocalcaemia caused by the combination of osteoblastic
metastases and a permanent postoperative hypoparathyroidism. The patient failed
to be treated with the conventional replacement therapy and was submitted
effectively to radionucleotide therapy with 153Sm.
PMID- 28512124
TI - Use of propranolol in a remote region of rural Guatemala to treat a large facial
infantile haemangioma.
AB - We present a female infant with a right-sided facial and neck haemangioma, from a
remote, resource-poor community in rural Guatemala. She received first-line
treatment, propranolol, with marked reduction in tumour size and erythema.
Treatment was stopped after 35 weeks due to recurrent diarrhoea and sustained
weight loss. Propranolol can be used to safely treat infants with haemangiomas in
remote, rural communities if there is adequate follow-up, education and
communication. Periocular haemangiomas should be treated promptly to avoid visual
impairment. Infants with large facial haemangiomas should be screened for
Posterior fossa anomalies, Hemangioma, Arterial anomalies, Cardiac anomalies, and
Eye anomalies (PHACE) syndrome, and specialists should be involved. The case also
highlights the difficulty of providing treatment for a complex illness when basic
health needs, such as food security and water sanitation, are limited.
PMID- 28512125
TI - Full-thickness gaping wound in the inguinal region of prenatal origin in an
extremely premature baby.
PMID- 28512126
TI - Tumor-associated myoepithelial cells promote the invasive progression of ductal
carcinoma in situ through activation of TGFbeta signaling.
AB - The normal myoepithelium has a tumor-suppressing nature and inhibits the
progression of ductal carcinoma in situ (DCIS) into invasive ductal carcinoma
(IDC). Conversely, a growing number of studies have shown that tumor-associated
myoepithelial cells have a tumor-promoting effect. Moreover, the exact role of
tumor-associated myoepithelial cells in the DCIS-to-IDC development remains
undefined. To address this, we explored the role of tumor-associated
myoepithelial cells in the DCIS-to-IDC progression. We developed a direct
coculture system to study the cell-cell interactions between DCIS cells and tumor
associated myoepithelial cells. Coculture studies indicated that tumor-associated
myoepithelial cells promoted the invasive progression of a DCIS cell model in
vitro, and mechanistic studies revealed that the interaction with DCIS cells
stimulated tumor-associated myoepithelial cells to secrete TGFbeta1, which
subsequently contributed to activating the TGFbeta/Smads pathway in DCIS cells.
We noted that activation of the TGFbeta signaling pathway promoted the epithelial
mesenchymal transition, basal-like phenotypes, stemness, and invasiveness of DCIS
cells. Importantly, xenograft studies further demonstrated that tumor-associated
myoepithelial cells enhanced the DCIS-to-IDC progression in vivo Furthermore, we
found that TGFbeta-mediated induction of oncogenic miR-10b-5p expression and down
regulation of RB1CC1, a miR-10b-5p-targeted tumor-suppressor gene, contributed to
the invasive progression of DCIS. Our findings provide the first experimental
evidence to directly support the paradigm that altered DCIS-associated
myoepithelial cells promote the invasive progression of DCIS into IDC via TGFbeta
signaling activation.
PMID- 28512128
TI - Refined topology model of the STT3/Stt3 protein subunit of the
oligosaccharyltransferase complex.
AB - The oligosaccharyltransferase complex, localized in the endoplasmic reticulum
(ER) of eukaryotic cells, is responsible for the N-linked glycosylation of
numerous protein substrates. The membrane protein STT3 is a highly conserved part
of the oligosaccharyltransferase and likely contains the active site of the
complex. However, understanding the catalytic determinants of this system has
been challenging, in part because of a discrepancy in the structural topology of
the bacterial versus eukaryotic proteins and incomplete information about the
mechanism of membrane integration. Here, we use a glycosylation mapping approach
to investigate these questions. We measured the membrane integration efficiency
of the mouse STT3-A and yeast Stt3p transmembrane domains (TMDs) and report a
refined topology of the N-terminal half of the mouse STT3-A. Our results show
that most of the STT3 TMDs are well inserted into the ER membrane on their own or
in the presence of the natural flanking residues. However, for the mouse STT3-A
hydrophobic domains 4 and 6 and yeast Stt3p domains 2, 3a, 3c, and 6 we measured
reduced insertion efficiency into the ER membrane. Furthermore, we mapped the
first half of the STT3-A protein, finding two extra hydrophobic domains between
the third and the fourth TMD. This result indicates that the eukaryotic STT3 has
13 transmembrane domains, consistent with the structure of the bacterial homolog
of STT3 and setting the stage for future combined efforts to interrogate this
fascinating system.
PMID- 28512127
TI - A structure-derived snap-trap mechanism of a multispecific serpin from the
dysbiotic human oral microbiome.
AB - Enduring host-microbiome relationships are based on adaptive strategies within a
particular ecological niche. Tannerella forsythia is a dysbiotic member of the
human oral microbiome that inhabits periodontal pockets and contributes to
chronic periodontitis. To counteract endopeptidases from the host or microbial
competitors, T. forsythia possesses a serpin-type proteinase inhibitor called
miropin. Although serpins from animals, plants, and viruses have been widely
studied, those from prokaryotes have received only limited attention. Here we
show that miropin uses the serpin-type suicidal mechanism. We found that, similar
to a snap trap, the protein transits from a metastable native form to a relaxed
triggered or induced form after cleavage of a reactive-site target bond in an
exposed reactive-center loop. The prey peptidase becomes covalently attached to
the inhibitor, is dragged 75 A apart, and is irreversibly inhibited. This
coincides with a large conformational rearrangement of miropin, which inserts the
segment upstream of the cleavage site as an extra beta-strand in a central beta
sheet. Standard serpins possess a single target bond and inhibit selected
endopeptidases of particular specificity and class. In contrast, miropin uniquely
blocked many serine and cysteine endopeptidases of disparate architecture and
substrate specificity owing to several potential target bonds within the reactive
center loop and to plasticity in accommodating extra beta-strands of variable
length. Phylogenetic studies revealed a patchy distribution of bacterial serpins
incompatible with a vertical descent model. This finding suggests that miropin
was acquired from the host through horizontal gene transfer, perhaps facilitated
by the long and intimate association of T. forsythia with the human gingiva.
PMID- 28512129
TI - Mammalian O-mannosylation of cadherins and plexins is independent of protein O
mannosyltransferases 1 and 2.
AB - Protein O-mannosylation is found in yeast and metazoans, and a family of
conserved orthologous protein O-mannosyltransferases is believed to initiate this
important post-translational modification. We recently discovered that the
cadherin superfamily carries O-linked mannose (O-Man) glycans at highly conserved
residues in specific extracellular cadherin domains, and it was suggested that
the function of E-cadherin was dependent on the O-Man glycans. Deficiencies in
enzymes catalyzing O-Man biosynthesis, including the two human protein O
mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular
dystrophies designated alpha-dystroglycanopathies, because deficient O-Man
glycosylation of alpha-dystroglycan disrupts laminin interaction with alpha
dystroglycan and the extracellular matrix. To explore the functions of O-Man
glycans on cadherins and protocadherins, we used a combinatorial gene-editing
strategy in multiple cell lines to evaluate the role of the two POMTs initiating
O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O
mannose beta-1,2-N-acetylglucosaminyltransferase, POMGnT1. Surprisingly, O
mannosylation of cadherins and protocadherins does not require POMT1 and/or POMT2
in contrast to alpha-dystroglycan, and moreover, the O-Man glycans on cadherins
are not elongated. Thus, the classical and evolutionarily conserved POMT O
mannosylation pathway is essentially dedicated to alpha-dystroglycan and a few
other proteins, whereas a novel O-mannosylation process in mammalian cells is
predicted to serve the large cadherin superfamily and other proteins.
PMID- 28512131
TI - H2S oxidation by nanodisc-embedded human sulfide quinone oxidoreductase.
AB - Buildup of hydrogen sulfide (H2S), which functions as a signaling molecule but is
toxic at high concentrations, is averted by its efficient oxidation by the
mitochondrial sulfide oxidation pathway. The first step in this pathway is
catalyzed by a flavoprotein, sulfide quinone oxidoreductase (SQR), which converts
H2S to a persulfide and transfers electrons to coenzyme Q via a flavin cofactor.
All previous studies on human SQR have used detergent-solubilized protein. Here,
we embedded human SQR in nanodiscs (ndSQR) and studied highly homogenous
preparations by steady-state and rapid-kinetics techniques. ndSQR exhibited
higher catalytic rates in its membranous environment than in its solubilized
state. Stopped-flow spectroscopic data revealed that transfer of the sulfane
sulfur from an SQR-bound cysteine persulfide intermediate to a small-molecule
acceptor is the rate-limiting step. The physiological acceptor of sulfane sulfur
from SQR has been the subject of controversy; we report that the kinetic analysis
of ndSQR is consistent with glutathione rather than sulfite being the predominant
acceptor at physiologically relevant concentrations of the respective
metabolites. The identity of the acceptor has an important bearing on how the
sulfide oxidation pathway is organized. Our data are more consistent with the
reaction sequence for sulfide oxidation being: H2S -> glutathione persulfide ->
sulfite -> sulfate, than with a more convoluted route that would result if
sulfite were the primary acceptor of sulfane sulfur. In summary, nanodisc
incorporated human SQR exhibits enhanced catalytic performance, and pre-steady
state kinetics characterization of the complete SQR catalytic cycle indicates
that GSH serves as the physiologically relevant sulfur acceptor.
PMID- 28512132
TI - Abortion by telemedicine: an equitable option for Irish women.
PMID- 28512134
TI - MANAGEMENT OF ENDOCRINE DISEASE: Suicide risk in patients with diabetes: a
systematic review and meta-analysis.
AB - BACKGROUND: Previous studies investigating the risk of suicide in diabetes
patients reported controversial findings. We did a systematic review and meta
analysis to comprehensively estimate the risk and incidence rate of suicide in
diabetic patients. METHODS: PubMed, EMBASE and PsycINFO were searched for
eligible studies. Random-effects meta-analysis was used to calculate the relative
risk (RR) and the incidence rate of suicide in diabetes patients. We also
calculated the proportion of deaths attributable to suicide among diabetes
patients. RESULTS: 54 studies were finally included, including 28 studies on the
suicide risk associated with diabetes, 47 studies on the incidence rate of
suicide and 45 studies on the proportion of deaths attributable to suicide. Meta
analysis showed that diabetes could significantly increase the risk of suicide
(RR = 1.56; 95% CI: 1.29-1.89; P < 0.001). Subgroup analysis showed that the RR
of suicide associated with type 1 diabetes was 2.25 (95% CI: 1.50-3.38; P <
0.001). The pooled incidence rate of suicide in patients with diabetes was 2.35
per 10 000 person-years (95% CI: 1.51-3.64). The pooled proportions of long-term
deaths attributable to suicide in type 1 diabetes patients and type 2 diabetes
patients were 7.7% (95% CI: 6.0-9.8) and 1.3% (95% CI: 0.6-2.6), respectively.
CONCLUSION: This meta-analysis suggests that diabetes can significantly increase
the risk of suicide. Suicide has an obvious contribution to mortality in diabetic
patients, especially among type 1 diabetes patients. Effective strategies to
decrease suicide risk and improve mental health outcomes in diabetes patients are
needed.
PMID- 28512130
TI - Combination therapy with octyl gallate and ferulic acid improves cognition and
neurodegeneration in a transgenic mouse model of Alzheimer's disease.
AB - To date, there is no effective Alzheimer's disease (AD)-modifying therapy.
Nonetheless, combination therapy holds promise, and nutraceuticals (natural
dietary compounds with therapeutic properties) and their synthetic derivatives
are well-tolerated candidates. We tested whether combination therapy with octyl
gallate (OG) and ferulic acid (FA) improves cognition and mitigates AD-like
pathology in the presenilin-amyloid beta-protein precursor (PSAPP) transgenic
mouse model of cerebral amyloidosis. One-year-old mice with established beta
amyloid plaques received daily doses of OG and FA alone or in combination for 3
months. PSAPP mice receiving combination therapy had statistically significant
improved cognitive function versus OG or FA single treatment on some (but not
all) measures. We also observed additional statistically significant reductions
in brain parenchymal and cerebral vascular beta-amyloid deposits as well as brain
amyloid beta-protein abundance in OG- plus FA-treated versus singly-treated PSAPP
mice. These effects coincided with enhanced nonamyloidogenic amyloid beta-protein
precursor (APP) cleavage, increased alpha-secretase activity, and beta-secretase
inhibition. We detected elevated expression of nonamyloidogenic soluble APP-alpha
and the alpha-secretase candidate, a disintegrin and metalloproteinase domain
containing protein 10. Correspondingly, amyloidogenic beta-carboxyl-terminal APP
fragment and beta-site APP-cleaving enzyme 1 expression levels were reduced. In
parallel, the ratio of beta- to alpha-carboxyl-terminal APP fragment was
decreased. OG and FA combination therapy strikingly attenuated neuroinflammation,
oxidative stress, and synaptotoxicity. Co-treatment afforded additional
statistically significant benefits on some, but not all, of these outcome
measures. Taken together, these data provide preclinical proof-of-concept for AD
combination therapy.
PMID- 28512133
TI - Quality of compounded hydrocortisone capsules used in the treatment of children.
AB - OBJECTIVES: Due to the lack of paediatric-licensed formulations, children are
often treated with individualized pharmacy-compounded adult medication. An
international web-based survey about the types of medication in children with
adrenal insufficiency (AI) revealed that the majority of paediatric physicians
are using pharmacy-compounded medication to treat children with AI. Observations
of loss of therapy control in children with congenital adrenal hyperplasia with
compounded hydrocortisone capsules and regained control after prescribing a new
hydrocortisone batch led to this 'real world' evaluation of pharmacy-compounded
paediatric hydrocortisone capsules. METHODS: Capsule samples were collected
randomly from volunteering parents of treated children suffering from congenital
adrenal hyperplasia from all over Germany. Analysis of net mass and
hydrocortisone content by high-performance liquid chromatography with ultraviolet
(HPLC-UV) detection method was performed based on the European Pharmacopeia.
RESULTS: In a total of 61 batches that were sent, 5 batches could not be analysed
because of missing dose information, insufficient number of capsules or were not
possible to be evaluated. Fifty-six batches containing 1125 capsules were
evaluated. 21.4% of the batches revealed insufficiency in uniformity of net mass
or drug content and additional 3.6% failed because they did not contain the
labelled drug. CONCLUSIONS: Compounded medication is a possible cause of
variation of steroid doses in children with adrenal insufficiency or congenital
adrenal hyperplasia, putting these vulnerable patients at risk of poor disease
control and adrenal crisis. These data may apply to other individualized
compounded oral medication as well, emphasizing the need for development of
licensed paediatric formulations approved by regulatory authorities.
PMID- 28512135
TI - Critical thinking in healthcare and education.
PMID- 28512136
TI - Physician age and patient outcomes.
PMID- 28512137
TI - Keep within target range of blood oxygen levels, new guideline recommends.
PMID- 28512138
TI - Factors Predicting Parent Anxiety Around Infant and Toddler Postoperative and
Pain.
AB - BACKGROUND AND OBJECTIVES: Understanding of parent anxiety and its effect on
infant postoperative pain is limited. We sought to identify psychological factors
associated with preoperative anxiety for parents of infants and toddlers
undergoing elective surgery and to determine whether parent anxiety is associated
with child postoperative pain. METHODS: This was a prospective cohort study of
consecutively eligible patients aged <=18 months undergoing craniofacial surgery
and their parents. Preoperative parent assessment included anxiety, coping,
parent health locus of control, and self-efficacy. Postoperative inpatient child
pain scores and medication use were collected. Analyses included hierarchical
multivariable logistic and linear regression models. RESULTS: Parents (n = 71,
90% female) of young children (mean age 6.6 months) undergoing cleft lip or
palate (n = 59) or cranial vault repair (n = 13) were enrolled. Maladaptive
coping (odds ratio 1.3; 95% confidence interval, 1.1-1.6), low parent self
efficacy (odds ratio 2.4; 95% confidence interval, 1.3-4.5), and external locus
of control (odds ratio 1.74; 95% confidence interval, 1.1-2.9) were independently
associated with high parental anxiety. The adjusted odds of moderate/severe
parent anxiety was 3.6 (95% confidence interval, 1.5-9.1) higher with each SD
increase in maladaptive coping. High parental anxiety was correlated with
significantly higher hospital mean child pain scores (1.87 points on 0-10 scale;
95% confidence interval, 0.42-3.70; P = .045). CONCLUSIONS: Coping and self
efficacy are modifiable factors that contribute to parent anxiety before and
during hospitalization and may be targets for intervention. Infants and toddlers
undergoing elective craniofacial surgery with highly anxious parents may be at
greater risk for higher postoperative pain.
PMID- 28512141
TI - Oncogene-inducible organoids as a miniature platform to assess cancer
characteristics.
AB - Direct effects of oncogenic proteins or inhibitor treatments on signaling
pathways are difficult to assess in transgenic mice. In this issue, Riemer et al.
(2017. J. Cell Biol. https://doi.org/10.1083/jcb.201610058) demonstrate that
oncogene-inducible organoids offer the experimental versatility of two
dimensional cell lines, while closely representing the in vivo situation.
PMID- 28512142
TI - A well-known potassium channel plays a critical role in lysosomes.
AB - Whole-endolysosome patch clamping presents new opportunities to identify and
characterize channels pivotal for these acidic organelles. In this issue (Wang et
al., 2017. J. Cell Biol. https://doi.org/10.1083/jcb.201612123), the
identification of a role for the large conductance calcium-activated potassium
channel brings new thinking about regulation of lysosome membrane potential and
function.
PMID- 28512139
TI - A genome-wide association meta-analysis on lipoprotein (a) concentrations
adjusted for apolipoprotein (a) isoforms.
AB - High lipoprotein (a) [Lp(a)] concentrations are an independent risk factor for
cardiovascular outcomes. Concentrations are strongly influenced by apo(a) kringle
IV repeat isoforms. We aimed to identify genetic loci associated with Lp(a)
concentrations using data from five genome-wide association studies (n = 13,781).
We identified 48 independent SNPs in the LPA and 1 SNP in the APOE gene region to
be significantly associated with Lp(a) concentrations. We also adjusted for
apo(a) isoforms to identify loci affecting Lp(a) levels independently from them,
which resulted in 31 SNPs (30 in the LPA, 1 in the APOE gene region). Seven SNPs
showed a genome-wide significant association with coronary artery disease (CAD)
risk. A rare SNP (rs186696265; MAF ~1%) showed the highest effect on Lp(a) and
was also associated with increased risk of CAD (odds ratio = 1.73, P = 3.35 * 10
30). Median Lp(a) values increased from 2.1 to 91.1 mg/dl with increasing number
of Lp(a)-increasing alleles. We found the APOE2-determining allele of rs7412 to
be significantly associated with Lp(a) concentrations (P = 3.47 * 10-10). Each
APOE2 allele decreased Lp(a) by 3.34 mg/dl corresponding to ~15% of the
population's mean values. Performing a gene-based test of association, including
suspected Lp(a) receptors and regulators, resulted in one significant association
of the TLR2 gene with Lp(a) (P = 3.4 * 10-4). In summary, we identified a large
number of independent SNPs in the LPA gene region, as well as the APOE2 allele,
to be significantly associated with Lp(a) concentrations.
PMID- 28512143
TI - Diverse roles of guanine nucleotide exchange factors in regulating collective
cell migration.
AB - Efficient collective migration depends on a balance between contractility and
cytoskeletal rearrangements, adhesion, and mechanical cell-cell communication,
all controlled by GTPases of the RHO family. By comprehensive screening of
guanine nucleotide exchange factors (GEFs) in human bronchial epithelial cell
monolayers, we identified GEFs that are required for collective migration at
large, such as SOS1 and beta-PIX, and RHOA GEFs that are implicated in
intercellular communication. Down-regulation of the latter GEFs differentially
enhanced front-to-back propagation of guidance cues through the monolayer and was
mirrored by down-regulation of RHOA expression and myosin II activity. Phenotype
based clustering of knockdown behaviors identified RHOA-ARHGEF18 and ARHGEF3
ARHGEF28-ARHGEF11 clusters, indicating that the latter may signal through other
RHO-family GTPases. Indeed, knockdown of RHOC produced an intermediate between
the two phenotypes. We conclude that for effective collective migration, the RHOA
GEFs -> RHOA/C -> actomyosin pathways must be optimally tuned to compromise
between generation of motility forces and restriction of intercellular
communication.
PMID- 28512144
TI - TOG-tubulin binding specificity promotes microtubule dynamics and mitotic spindle
formation.
AB - XMAP215, CLASP, and Crescerin use arrayed tubulin-binding tumor overexpressed
gene (TOG) domains to modulate microtubule dynamics. We hypothesized that TOGs
have distinct architectures and tubulin-binding properties that underlie each
family's ability to promote microtubule polymerization or pause. As a model, we
investigated the pentameric TOG array of a Drosophila melanogaster XMAP215
member, Msps. We found that Msps TOGs have distinct architectures that bind
either free or polymerized tubulin, and that a polarized array drives microtubule
polymerization. An engineered TOG1-2-5 array fully supported Msps-dependent
microtubule polymerase activity. Requisite for this activity was a TOG5-specific
N-terminal HEAT repeat that engaged microtubule lattice-incorporated tubulin.
TOG5-microtubule binding maintained mitotic spindle formation as deleting or
mutating TOG5 compromised spindle architecture and increased the mitotic index.
Mad2 knockdown released the spindle assembly checkpoint triggered when TOG5
microtubule binding was compromised, indicating that TOG5 is essential for
spindle function. Our results reveal a TOG5-specific role in mitotic fidelity and
support our hypothesis that architecturally distinct TOGs arranged in a sequence
specific order underlie TOG array microtubule regulator activity.
PMID- 28512146
TI - Science Signaling Podcast for 16 May 2017: Vibrio rewires host cells.
AB - This Podcast features a conversation with Kim Orth and Nicole De Nisco, authors
of a Research Resource that appears in the 16 May 2017 issue of Science
Signaling, about how the marine bacterium Vibrio parahaemolyticus rewires host
cell signaling networks. V. parahaemolyticus thrives in warm brackish waters and
infects both shellfish and finfish. This bacterium causes gastroenteritis when
humans consume contaminated seafood that is raw or undercooked. V.
parahaemolyticus delivers virulence factors into host cells through two different
type 3 secretion systems (T3SSes). Whereas T3SS2 mediates gastroenteritis, T3SS1
is required for the bacterium to survive in its natural environment and delivers
virulence factors that target conserved cellular processes. De Nisco et al
examined transcriptional changes in human cells infected with a strain of V.
parahaemolyticus that lacked T3SS2 but had an intact T3SS1. They found that the
virulence factors delivered through T3SS1 initially induced transcriptional
changes that promoted cell survival, then later repressed prosurvival signaling
to induce cell death.Listen to Podcast.
PMID- 28512145
TI - The cytotoxic type 3 secretion system 1 of Vibrio rewires host gene expression to
subvert cell death and activate cell survival pathways.
AB - Bacterial effectors potently manipulate host signaling pathways. The marine
bacterium Vibrio parahaemolyticus (V. para) delivers effectors into host cells
through two type 3 secretion systems (T3SSs). T3SS1 is vital for V. para survival
in the environment, whereas T3SS2 causes acute gastroenteritis in human hosts.
Although the natural host is undefined, T3SS1 effectors attack highly conserved
cellular processes and pathways to orchestrate nonapoptotic cell death. To
understand how the concerted action of T3SS1 effectors globally affects host cell
signaling, we compared gene expression changes over time in primary fibroblasts
infected with V. para that have a functional T3SS1 (T3SS1+) to those in cells
infected with V. para lacking T3SS1 (T3SS1-). Overall, the host transcriptional
response to both T3SS1+ and T3SS1-V. para was rapid, robust, and temporally
dynamic. T3SS1 rewired host gene expression by specifically altering the
expression of 398 genes. Although T3SS1 effectors targeted host cells at the
posttranslational level to cause cytotoxicity, V. para T3SS1 also precipitated a
host transcriptional response that initially activated cell survival and
repressed cell death networks. The increased expression of several key
prosurvival transcripts mediated by T3SS1 depended on a host signaling pathway
that is silenced posttranslationally later in infection. Together, our analysis
reveals a complex interplay between the roles of T3SS1 as both a transcriptional
and posttranslational manipulator of host cell signaling.
PMID- 28512148
TI - Erratum for the Research Article: "Reactive oxygen species induce virus
independent MAVS oligomerization in systemic lupus erythematosus" by I. A.
Buskiewicz, T. Montgomery, E. C. Yasewicz, S. A. Huber, M. P. Murphy, R. C.
Hartley, R. Kelly, M. K. Crow, A. Perl, R. C. Budd, A. Koenig.
PMID- 28512149
TI - Quorum sensing to repress virulence.
AB - A quorum-sensing system of an insect endosymbiont enables the bacterium to
establish persistent infection by inhibiting the expression of virulence genes.
PMID- 28512147
TI - Nrf2 inactivation enhances placental angiogenesis in a preeclampsia mouse model
and improves maternal and fetal outcomes.
AB - Placental activation of the renin-angiotensin system (RAS) plays a key role in
the pathogenesis of preeclampsia. Reactive oxygen species (ROS) are thought to
affect placental angiogenesis, which is critical for preventing preeclampsia
pathology. We examined the role of ROS in preeclampsia by genetically modifying
the Keap1-Nrf2 pathway, a cellular antioxidant defense system, in a mouse model
of RAS-induced preeclampsia. Nrf2 deficiency would be expected to impair cellular
antioxidant responses; however, Nrf2 deficiency in preeclamptic mice improved
maternal and fetal survival, ameliorated intra-uterine growth retardation, and
augmented oxidative DNA damage. Furthermore, the placentas of Nrf2-deficient mice
had increased endothelial cell proliferation with dense vascular networks. In
contrast, the placentas of preeclamptic mice with overactive Nrf2 showed
repressed angiogenesis, which was associated with decreased expression of genes
encoding angiogenic chemokines and cytokines. Our findings support the notion
that ROS-mediated signaling is essential for maintaining placental angiogenesis
in preeclampsia and may provide mechanistic insight into the negative results of
clinical trials for antioxidants in preeclampsia.
PMID- 28512153
TI - New connections: The duality of ROS in angiogenesis.
AB - Depending on the tissue and context, ROS can either stimulate or suppress blood
vessel formation.
PMID- 28512154
TI - Glucose autoregulation is the dominant component of the hormone-independent
counterregulatory response to hypoglycemia in the conscious dog.
AB - The contribution of hormone-independent counterregulatory signals in defense of
insulin-induced hypoglycemia was determined in adrenalectomized, overnight-fasted
conscious dogs receiving hepatic portal vein insulin infusions at a rate 20-fold
basal. Either euglycemia was maintained (group 1) or hypoglycemia (~45 mg/dl) was
allowed to occur. There were three hypoglycemic groups: one in which hepatic
autoregulation against hypoglycemia occurred in the absence of sympathetic
nervous system input (group 2), one in which autoregulation occurred in the
presence of norepinephrine (NE) signaling to fat and muscle (group 3), and one in
which autoregulation occurred in the presence of NE signaling to fat, muscle, and
liver (group 4). Average net hepatic glucose balance (NHGB) during the last hour
for groups 1-4 was -0.7 +/- 0.1, 0.3 +/- 0.1 (P < 0.01 vs. group 1), 0.7 +/- 0.1
(P = 0.01 vs. group 2), and 0.8 +/- 0.1 (P = 0.7 vs. group 3) mg.kg-1.min-1,
respectively. Hypoglycemia per se (group 2) increased NHGB by causing an
inhibition of net hepatic glycogen synthesis. NE signaling to fat and muscle
(group 3) increased NHGB further by mobilizing gluconeogenic precursors resulting
in a rise in gluconeogenesis. Lowering glucose per se decreased nonhepatic
glucose uptake by 8.9 mg.kg-1.min-1, and the addition of increased neural
efferent signaling to muscle and fat blocked glucose uptake further by 3.2 mg.kg
1.min-1 The addition of increased neural efferent input to liver did not affect
NHGB or nonhepatic glucose uptake significantly. In conclusion, even in the
absence of increases in counterregulatory hormones, the body can defend itself
against hypoglycemia using glucose autoregulation and increased neural efferent
signaling, both of which stimulate hepatic glucose production and limit glucose
utilization.
PMID- 28512156
TI - Effects of metformin on compensatory pancreatic beta-cell hyperplasia in mice fed
a high-fat diet.
AB - Metformin has been widely used for the treatment of type 2 diabetes. However, the
effect of metformin on pancreatic beta-cells remains controversial. In this
study, we investigated the impacts of treatment with metformin on pancreatic beta
cells in a mouse model fed a high-fat diet (HFD), which triggers adaptive beta
cell replication. An 8-wk treatment with metformin improved insulin resistance
and suppressed the compensatory beta-cell hyperplasia induced by HFD-feeding. In
contrast, the increment in beta-cell mass arising from 60 wk of HFD feeding was
similar in mice treated with and those treated without metformin. Interestingly,
metformin suppressed beta-cell proliferation induced by 1 wk of HFD feeding
without any changes in insulin resistance. Metformin directly suppressed glucose
induced beta-cell proliferation in islets and INS-1 cells in accordance with a
reduction in mammalian target of rapamycin phosphorylation. Taken together,
metformin suppressed HFD-induced beta-cell proliferation independent of the
improvement of insulin resistance, partly via direct actions.
PMID- 28512155
TI - Functional high-intensity training improves pancreatic beta-cell function in
adults with type 2 diabetes.
AB - Type 2 diabetes (T2D) is characterized by reductions in beta-cell function and
insulin secretion on the background of elevated insulin resistance. Aerobic
exercise has been shown to improve beta-cell function, despite a subset of T2D
patients displaying "exercise resistance." Further investigations into the
effectiveness of alternate forms of exercise on beta-cell function in the T2D
patient population are needed. We examined the effect of a novel, 6-wk CrossFit
functional high-intensity training (F-HIT) intervention on beta-cell function in
12 sedentary adults with clinically diagnosed T2D (54 +/- 2 yr, 166 +/- 16 mg/dl
fasting glucose). Supervised training was completed 3 days/wk, comprising
functional movements performed at a high intensity in a variety of 10- to 20-min
sessions. All subjects completed an oral glucose tolerance test and
anthropometric measures at baseline and following the intervention. The mean
disposition index, a validated measure of beta-cell function, was significantly
increased (PRE: 8.4 +/- 3.1, POST: 11.5 +/- 3.5, P = 0.02) after the
intervention. Insulin processing inefficiency in the beta-cell, expressed as the
fasting proinsulin-to-insulin ratio, was also reduced (PRE: 2.40 +/- 0.37, POST:
1.78 +/- 0.30, P = 0.04). Increased beta-cell function during the early-phase
response to glucose correlated significantly with reductions in abdominal body
fat (R2 = 0.56, P = 0.005) and fasting plasma alkaline phosphatase (R2 = 0.55, P
= 0.006). Mean total body-fat percentage decreased significantly (Delta: -1.17
0.30%, P = 0.003), whereas lean body mass was preserved (Delta: +0.05 +/- 0.68
kg, P = 0.94). We conclude that F-HIT is an effective exercise strategy for
improving beta-cell function in adults with T2D.
PMID- 28512157
TI - IL-22BP dictates characteristics of Peyer's patch follicle-associated epithelium
for antigen uptake.
AB - Interleukin-22 (IL-22) acts protectively and harmfully on intestinal tissue
depending on the situation; therefore, IL-22 signaling needs to be tightly
regulated. IL-22 binding protein (IL-22BP) binds IL-22 to inhibit IL-22
signaling. It is expressed in intestinal and lymphoid tissues, although its
precise distribution and roles have remained unclear. In this study, we show that
IL-22BP is highly expressed by CD11b+CD8alpha- dendritic cells in the
subepithelial dome region of Peyer's patches (PPs). We found that IL-22BP blocks
IL-22 signaling in the follicle-associated epithelium (FAE) covering PPs,
indicating that IL-22BP plays a role in regulating the characteristics of the
FAE. As expected, FAE of IL-22BP-deficient (Il22ra2-/-) mice exhibited altered
properties such as the enhanced expression of mucus and antimicrobial proteins as
well as prominent fucosylation, which are normally suppressed in FAE.
Additionally, Il22ra2-/- mice exhibited the decreased uptake of bacterial
antigens into PPs without affecting M cell function. Our present study thus
demonstrates that IL-22BP promotes bacterial uptake into PPs by influencing FAE
gene expression and function.
PMID- 28512158
TI - Association between changes in fat distribution and biomarkers for breast cancer.
AB - We assessed the associations between changes in total and abdominal fat and
changes in biomarkers for breast cancer risk using data of the SHAPE-2 trial. In
the SHAPE-2 trial, 243 postmenopausal overweight women were included. The
intervention in this trial consisted of 5-6 kg weight loss either by diet only or
exercise plus diet. After 16 weeks, we measured serum sex hormones, inflammatory
markers, total body fat (measured by DEXA scan) and intra and subcutaneous
abdominal fat (measured by MRI). Associations between changes in different body
fat depots and biomarkers were analysed by linear regression using the study
cohort irrespective of randomisation to make maximal use of the distribution of
changes in fat measures. We found that a loss in total body fat was associated
with favourable changes in free oestradiol, free testosterone, leptin and sex
hormone binding globulin (SHBG). The loss of intra-abdominal fat was associated
with a decrease in free testosterone, hsCRP and leptin, and an increase in SHBG.
In the multivariable analysis, the best fitted models for the biomarkers free
oestradiol, SHBG leptin and adiponectin included only total body fat. For free
testosterone, this was subcutaneous abdominal fat, and for hsCRP and IL-6, only
intra-abdominal fat change was important. For IL-6 and adiponectin, however,
associations were weak and not significant. We conclude that, in our population
of healthy overweight postmenopausal women, loss of fat at different body
locations was associated with changes in different types of biomarkers, known to
be related to risk of breast cancer.
PMID- 28512159
TI - Employing Extracellular Volume Cardiovascular Magnetic Resonance Measures of
Myocardial Fibrosis to Foster Novel Therapeutics.
AB - Quantifying myocardial fibrosis (MF) with myocardial extracellular volume
measures acquired during cardiovascular magnetic resonance promises to transform
clinical care by advancing pathophysiologic understanding and fostering novel
therapeutics. Extracellular volume quantifies MF by measuring the extracellular
compartment depicted by the myocardial uptake of contrast relative to plasma. MF
is a key domain of dysfunctional but viable myocardium among others (eg,
microvascular dysfunction and cardiomyocyte/mitochondrial dysfunction). Although
anatomically distinct, these domains may functionally interact. MF represents
pathological remodeling in the heart associated with cardiac dysfunction and
adverse outcomes likely mediated by interactions with the microvasculature and
the cardiomyocyte. Reversal of MF improves key measures of cardiac dysfunction,
so reversal of MF represents a likely mechanism for improved outcomes. Instead of
characterizing the myocardium as homogenous tissue and using important yet still
generic descriptors, such as thickness (hypertrophy) and function (diastolic or
systolic), which lack mechanistic specificity, paradigms of cardiac disease have
evolved to conceptualize myocardial disease and patient vulnerability based on
the extent of disease involving its various compartments. Specifying myocardial
compartmental involvement may then implicate cellular/molecular disease pathways
for treatment and targeted pharmaceutical development and above all highlight the
role of the cardiac-specific pathology in heart failure among myriad other
changes in the heart and beyond. The cardiology community now requires phase 2
and 3 clinical trials to examine strategies for the regression/prevention of MF
and eventually biomarkers to identify MF without reliance on cardiovascular
magnetic resonance. It seems likely that efficacious antifibrotic therapy will
improve outcomes, but definitive data are needed.
PMID- 28512160
TI - Improving the Impact of Peritoneal Dialysis Research.
PMID- 28512161
TI - Should Nephrologists Promote Peritoneal Dialysis as a Bridge to Transplantation?
PMID- 28512162
TI - Increase in Extracellular Hydration Status After Initiating Peritoneal Dialysis
Electively.
AB - Renal replacement therapy is designed to treat uremic symptoms and correct
hypervolemia. We hypothesized that starting peritoneal dialysis (PD) should
reduce overhydration, and we measured body composition and hydration status using
bioimpedance in PD patients prior to training and then at the first assessment of
peritoneal membrane function. We studied 100 consecutive patients with a planned
start to PD, without peritoneal infections or mechanical catheter problems, mean
age 54.7 +/- 17.1 years, 57% male and 25% diabetic. Extracellular water (ECW)
overhydration increased from -0.06 (-1.21 to 0.97) L to 0.96 (0.50 to 3.01) L, p
< 0.001. Fat mass increased from 22.7 +/- 11.1 to 23.7 +/- 11.3 kg, p = 0.007).
The change in ECW/total body water (TBW) was associated with age (beta 0.065, p <
0.001), increasing comorbidity (beta 1.107, p = 0.005), faster peritoneal protein
transport (beta 1.84, p < 0.04), and negatively with serum albumin (beta -0.208,
p < 0.001), and residual renal function (beta -0.725, p = 0.026). Patients who
had an increase in ECW/TBW had higher C-reactive protein (CRP) both before
starting (16.8 +/- 24.1 vs 7.7 +/- 18.9 mg/L), and when established on PD (15.0
+/- 31.8 vs 4.6 +/- 5.1 mg/L), p < 0.05. Rather than a reduction in ECW hydration
status, overhydration increased after starting PD. This was greater for older
more comorbid patients and those with an inflammatory milieu and lower residual
renal function. These factors should be considered when deciding upon initial PD
prescriptions to limit ECW overhydration before information on peritoneal
membrane function becomes available.
PMID- 28512163
TI - Retroperitoneal Laparoscopic Radical Nephrectomy Allows Continuation of
Peritoneal Dialysis in Patients with End-Stage Renal Disease.
AB - Patient outcomes for retroperitoneal laparoscopic radical nephrectomy (RLRN) in
adults on peritoneal dialysis (PD) have not been described in the literature.
This is the first series on the successful application of RLRN for renal cell
carcinoma (RCC) among adults with end-stage renal disease (ESRD) on PD. In our
series of 5 patients, all were able to promptly resume PD, no wound complications
were noted at postoperative visits, and no evidence of recurrence was identified
on surveillance imaging at follow-up. We propose that RLRN should be considered
in PD patients as it allows immediate reinstitution of PD and prevents the
morbidity and complications associated with interim hemodialysis.
PMID- 28512165
TI - The Use of the Galactomannan Test to Diagnose Peritoneal Dialysis-Associated
Penicillium Peritonitis.
PMID- 28512164
TI - Time to Positivity of Bacteria Cultures in Peritoneal Dialysis Fluid: Evaluation
of Different Laboratory Techniques.
AB - Patients with chronic kidney disease on peritoneal dialysis (PD) are susceptible
to infections, with peritonitis being the primary cause of dropout. Peritoneal
fluid culture is one of the essential elements for proper diagnosis and
peritonitis treatment. The aim of this study was to compare the time required to
obtain a positive culture using different laboratory methods. An in vitro cross
sectional study was conducted comparing different techniques for preparation and
culture of bacteria in peritoneal fluid. The research was carried out with 21
sterile dialysis bags and 21 PD bags containing peritoneal fluid drained from
patients without peritonitis. Fluids from the 42 PD bags were contaminated by
injecting a coagulase-negative Staphylococcus suspension and then prepared for
culture using 4 distinct techniques: A - direct culture; B - post-centrifugation
culture; C - direct culture after 4 h sedimentation; and D - culture after 4 h
sedimentation and centrifugation. This was followed by seeding. In the 21
contaminated sterile bags, mean times to obtain a positive culture with
techniques D (19.6 h +/- 2.6) and C (19.1 h +/- 2.3) were longer than with
technique A (15.8 h +/- 3.0; p < 0.01), but not statistically different from
group B (19.0 h +/- 3.2). The same occurred in the 21 bags drained from patients,
with mean times for techniques D (14.0 h +/- 1.9) and C (14.5 h +/- 1.7) being
longer than technique A (12.22 h +/- 1.94; p < 0.05) but not statistically
different from technique B (13.2 h +/- 1.3). The sedimentation and centrifugation
steps seem to be unnecessary and may delay antibiotic sensitivity test results by
approximately 8 hours.
PMID- 28512166
TI - A Case of Peritoneal Dialysis-Associated Peritonitis Caused by Agromyces
mediolanus.
PMID- 28512167
TI - Candida parapsilosis Peritonitis-Macroscopic and Microscopic Appearances.
PMID- 28512168
TI - Hydrocele Caused by Peritoneal Fluid Leakage Through Inguinal Canal.
PMID- 28512169
TI - Eosinophilia in Peritoneal Effluent Due To a Levonorgestrel-Releasing
Intrauterine System in a Woman on Peritoneal Dialysis.
PMID- 28512170
TI - Deconstruction of Interhospital Transfer Workflow in Large Vessel Occlusion: Real
World Data in the Thrombectomy Era.
AB - BACKGROUND AND PURPOSE: Interhospital transfer is a critical component in the
treatment of acute anterior circulation large vessel occlusive stroke transferred
for mechanical thrombectomy. Real-world data for benchmarking and theoretical
modeling are limited. We sought to characterize transfer workflow from primary
stroke center (PSC) to comprehensive stroke center after the publication of
positive thrombectomy trials. METHODS: Consecutive patients transferred from 3
high-volume PSCs to a single comprehensive stroke center between January 2015 and
August 2016 were included in a retrospective study. Factors associated with key
time metrics were analyzed with emphasis on PSC intrahospital workflow. RESULTS:
Sixty-seven patients were identified. Median age was 74 years (interquartile
range [IQR], 63.5-78) and National Institutes of Health Stroke Scale 17 (IQR, 12
21). Median transfer time measured by PSC-door-to-comprehensive stroke center
door was 128 minutes (IQR, 107-164), of which 82.8% was spent at PSCs (door-in
door-out [DIDO]; 106 minutes; IQR, 86-143). The lengthiest component of DIDO was
computed-tomography-to-retrieval-request (median 59.5 minutes; IQR, 44-83). The
37.3% had DIDO exceeding 120 minutes. DIDO times differed significantly between
PSCs (P=0.01). In multivariate analyses, rerecruiting the initial ambulance crew
for transfer (P<0.01) and presentation during working hours (P=0.04) were
associated with shorter DIDO times. CONCLUSIONS: In a metropolitan hub-and-spoke
network, PSC-door-to-comprehensive stroke center-door and DIDO times are long
even in high-volume PSCs. Improving PSC workflow represents a major opportunity
to expedite mechanical thrombectomy and improve patient outcomes.
PMID- 28512171
TI - Effect of message congruency on attention and recall in pictorial health warning
labels.
AB - OBJECTIVE: The nine pictorial health warning labels (PWLs) proposed by the US
Food and Drug Administration vary in format and feature of visual and textual
information. Congruency is the degree to which visual and textual features
reflect a common theme. This characteristic can affect attention and recall of
label content. This study investigates the effect of congruency in PWLs on
smoker's attention and recall of label content. METHODS: 120 daily smokers were
randomly assigned to view either congruent or incongruent PWLs, while having
their eye movements recorded. Participants were asked to recall label content
immediately after exposure and 5 days later. RESULTS: Overall, the image was
viewed more and recalled better than the text. Smokers in the incongruent
condition spent more time focusing on the text than smokers in the congruent
condition (p=0.03), but dwell time of the image did not differ. Despite lower
dwell time on the text, smokers in the congruent condition were more likely to
correctly recall it on day 1 (p=0.02) and the risk message of the PWLs on both
day 1 (p=0.01) and day 5 (p=0.006) than smokers in the incongruent condition.
CONCLUSIONS: This study identifies an important design feature of PWLs and
demonstrates objective differences in how smokers process PWLs. Our results
suggest that message congruency between visual and textual information is
beneficial to recall of label content. Moreover, images captured and held
smokers' attention better than the text.
PMID- 28512172
TI - In Vivo Hemin Conditioning Targets the Vascular and Immunologic Compartments and
Restrains Prostate Tumor Development.
AB - Purpose: Conditioning strategies constitute a relatively unexplored and exciting
opportunity to shape tumor fate by targeting the tumor microenvironment. In this
study, we assessed how hemin, a pharmacologic inducer of heme oxygenase-1 (HO-1),
has an impact on prostate cancer development in an in vivo conditioning
model.Experimental Design: The stroma of C57BL/6 mice was conditioned by
subcutaneous administration of hemin prior to TRAMP-C1 tumor challenge.
Complementary in vitro and in vivo assays were performed to evaluate hemin effect
on both angiogenesis and the immune response. To gain clinical insight, we used
prostate cancer patient-derived samples in our studies to assess the expression
of HO-1 and other relevant genes.Results: Conditioning resulted in increased
tumor latency and decreased initial growth rate. Histologic analysis of tumors
grown in conditioned mice revealed impaired vascularization. Hemin-treated human
umbilical vein endothelial cells (HUVEC) exhibited decreased tubulogenesis in
vitro only in the presence of TRAMP-C1-conditioned media. Subcutaneous hemin
conditioning hindered tumor-associated neovascularization in an in vivo Matrigel
plug assay. In addition, hemin boosted CD8+ T-cell proliferation and
degranulation in vitro and antigen-specific cytotoxicity in vivo A significant
systemic increase in CD8+ T-cell frequency was observed in preconditioned tumor
bearing mice. Tumors from hemin-conditioned mice showed reduced expression of
galectin-1 (Gal-1), key modulator of tumor angiogenesis and immunity, evidencing
persistent remodeling of the microenvironment. We also found a subset of prostate
cancer patient-derived xenografts and prostate cancer patient samples with mild
HO-1 and low Gal-1 expression levels.Conclusions: These results highlight a novel
function of a human-used drug as a means of boosting the antitumor response. Clin
Cancer Res; 23(17); 5135-48. (c)2017 AACR.
PMID- 28512173
TI - Clinical Utility of Risk Models to Refer Patients with Adnexal Masses to
Specialized Oncology Care: Multicenter External Validation Using Decision Curve
Analysis.
AB - Purpose: To evaluate the utility of preoperative diagnostic models for ovarian
cancer based on ultrasound and/or biomarkers for referring patients to
specialized oncology care. The investigated models were RMI, ROMA, and 3 models
from the International Ovarian Tumor Analysis (IOTA) group [LR2, ADNEX, and the
Simple Rules risk score (SRRisk)].Experimental Design: A secondary analysis of
prospectively collected data from 2 cross-sectional cohort studies was performed
to externally validate diagnostic models. A total of 2,763 patients (2,403 in
dataset 1 and 360 in dataset 2) from 18 centers (11 oncology centers and 7
nononcology hospitals) in 6 countries participated. Excised tissue was
histologically classified as benign or malignant. The clinical utility of the
preoperative diagnostic models was assessed with net benefit (NB) at a range of
risk thresholds (5%-50% risk of malignancy) to refer patients to specialized
oncology care. We visualized results with decision curves and generated bootstrap
confidence intervals.Results: The prevalence of malignancy was 41% in dataset 1
and 40% in dataset 2. For thresholds up to 10% to 15%, RMI and ROMA had a lower
NB than referring all patients. SRRisks and ADNEX demonstrated the highest NB. At
a threshold of 20%, the NBs of ADNEX, SRrisks, and RMI were 0.348, 0.350, and
0.270, respectively. Results by menopausal status and type of center (oncology
vs. nononcology) were similar.Conclusions: All tested IOTA methods, especially
ADNEX and SRRisks, are clinically more useful than RMI and ROMA to select
patients with adnexal masses for specialized oncology care. Clin Cancer Res;
23(17); 5082-90. (c)2017 AACR.
PMID- 28512175
TI - 2015/2016 Quality Risk Management Benchmarking Survey.
AB - This paper investigates the concept of quality risk management (QRM) maturity as
it applies to the pharmaceutical and biopharmaceutical industries, using the
results and analysis from a QRM benchmarking survey conducted in 2015 and 2016.
QRM maturity can be defined as the effectiveness and efficiency of a quality risk
management program, moving beyond "check-the-box" compliance with guidelines such
as ICH Q9 Quality Risk Management, to explore the value QRM brings to business
and quality operations. While significant progress has been made towards full
adoption of QRM principles and practices across industry, the full benefits of
QRM have not yet been fully realized. The results of the QRM Benchmarking Survey
indicate that the pharmaceutical and biopharmaceutical industries are
approximately halfway along the journey towards full QRM maturity.LAY ABSTRACT:
The management of risks associated with medicinal product quality and patient
safety are an important focus for the pharmaceutical and biopharmaceutical
industries. These risks are identified, analyzed, and controlled through a
defined process called quality risk management (QRM), which seeks to protect the
patient from potential quality-related risks. This paper summarizes the outcomes
of a comprehensive survey of industry practitioners performed in 2015 and 2016
that aimed to benchmark the level of maturity with regard to the application of
QRM. The survey results and subsequent analysis revealed that the pharmaceutical
and biopharmaceutical industries have made significant progress in the management
of quality risks over the last ten years, and they are roughly halfway towards
reaching full maturity of QRM.
PMID- 28512176
TI - Extractables Screening of Polypropylene Resins Used in Pharmaceutical Packaging
for Safety Hazards.
AB - Pharmaceutical products are packaged in containers so that they can be
manufactured, distributed, and used. Because extractables from such containers
are precursors of leachable impurities in the product, extractables represent
potential hazards to user safety. Polypropylene resins are frequently used as
materials of construction for packaging of liquid parenteral drug products. Thus,
extractables profiling of polypropylene resins may be an effective means of
hazard identification associated with the resin's safe use. Twenty-one
polypropylene resins were extracted using aqueous and organic extraction
solvents, and the resulting extracts were screened for extractables using
appropriate general chemistry, chromatographic, and spectroscopic methodologies.
The resulting extractables profiles were toxicologically reviewed by a defined
process to identify potential hazards given a specified therapeutic application
involving long-term use of a large-volume aqueous parenteral drug product. The
organic extractables profiles of individual polypropylene resins were variable in
terms of the individual extractable identified and their extracted levels,
consistent with high variability in polypropylene resin formulations and
pharmaceutical product manufacturing. However, the profiles were similar in terms
of the groups of extractables measured. Thus, for example, all the resins had
extractables associated with antioxidants, as all the resins contained
antioxidants but the specific extractables for a given resin depended on the
specific antioxidants present in that resin. Few of the targeted extractable
elements were present in the extracts at measurable levels, although most resins
had measurable levels of extracted aluminum, silicon, and alkali and alkaline
earths. A worst-case extractables profile (all the extractables measured in
individual resins at their highest levels) was toxicologically reviewed
considering an aqueous large-volume parenteral drug product. This review
established certain extractables as potential hazards whose actual toxicological
safety risk assessment would require more rigorous data and a more rigorous
process than those used for hazard identification.LAY ABSTRACT: Packages used to
contain aqueous parenteral drug products may be made of polypropylene. During
storage, extractables from the polypropylene may leach out of the container and
accumulate in the drug product, where they could affect product quality and/or
safety. In this study, 21 polypropylene resins were characterized with respect to
their organic and elemental extractables profiles. A worst-case extractables
profile (highest level of all the extractables identified) was toxicologically
assessed to establish potentially hazardous extractables. Certain extractables
were established as potential hazards whose actual toxicological safety risk
assessment would require more rigorous data and a more rigorous process than
those used for hazard identification.
PMID- 28512174
TI - Dynamic Changes in PD-L1 Expression and Immune Infiltrates Early During Treatment
Predict Response to PD-1 Blockade in Melanoma.
AB - Purpose: Disruption of PD-L1/cytotoxic T-cell PD-1 signaling by immune checkpoint
inhibitors improves survival in cancer patients. This study sought to identify
changes in tumoral PD-L1 expression and tumor-associated immune cell flux with
anti-PD-1 therapies in patients with melanoma, particularly early during
treatment, and correlate them with treatment response.Experimental Design: Forty
six tumor biopsies from 23 patients with unresectable AJCC stage III/IV melanoma
receiving pembrolizumab/nivolumab were analyzed. Biopsies were collected prior to
(PRE, n = 21), within 2 months of commencing treatment (EDT, n = 20) and on
disease progression after previous response (PROG, n = 5). Thirteen patients
responded (defined as CR, PR, or durable SD by RECIST/irRC criteria), and 10 did
not respond.Results: PRE intratumoral and peritumoral PD-1+ T-cell densities were
sevenfold (P = 0.006) and fivefold higher (P = 0.011), respectively, in
responders compared with nonresponders and correlated with degree of radiologic
tumor response (r = -0.729, P = 0.001 and r = -0.725, P = 0.001, respectively).
PRE PD-L1 expression on tumor and macrophages was not significantly different
between the patient groups, but tumoral PD-L1 and macrophage PD-L1 expression was
higher in the EDT of responders versus nonresponders (P = 0.025 and P = 0.033).
Responder EDT biopsies (compared with PRE) also showed significant increases in
intratumoral CD8+ lymphocytes (P = 0.046) and intratumoral CD68+ macrophages (P =
0.046).Conclusions: Higher PRE PD-1+ T cells in responders suggest active
suppression of an engaged immune system that is disinhibited by anti-PD-1
therapies. Furthermore, immunoprofiling of EDT biopsies for increased PD-L1
expression and immune cell infiltration showed greater predictive utility than
PRE biopsies and may allow better selection of patients most likely to benefit
from anti-PD-1 therapies and warrants further evaluation. Clin Cancer Res;
23(17); 5024-33. (c)2017 AACR.
PMID- 28512177
TI - Evaluation of Novel Process Indicators for Rapid Monitoring of Hydrogen Peroxide
Decontamination Processes.
AB - Geobacillus stearothermophilus spores on stainless steel discs are routinely used
as biological indicators for the validation of hydrogen peroxide bio
decontamination processes. Given ongoing concerns about the reliability and
response time of biological indicators, we explored the potential for an enzyme
based approach to decontamination process evaluation. Thermostable adenylate
kinase enzyme was coated onto a solid support and exposed to hydrogen peroxide
vapour, in parallel with standard commercial 6-log biological indicators, during
a series of vapour-phase hydrogen peroxide cycles in a flexible film isolator.
The exposed biological indicators were enumerated to define the degree of kill at
different time intervals and the results compared to the thermostable adenylate
kinase values, as determined by measuring adenosine triphosphate produced by
residual active enzyme. Both biological indicators and the thermostable adenylate
kinase indicators exhibited a biphasic inactivation profile during the process.
There was significant variance between individual cycles, with some cycles
showing complete inactivation of the biological indicators to the limit of
detection of the assay, within 6 min, whereas biological indicators in some
cycles were inactivated at a time greater than 12 min. The log-kill of the
biological indicators at intermediate time points were plotted and compared to
the fully quantifiable measurements derived from the thermostable adenylate
kinase indicators at the same time points. The results demonstrated very similar
inactivation profiles for the enzyme and for the biological indicators, thus it
was possible to define a relationship between relative light units measurement
and biological indicator kill. This indicates that it is possible to use
thermostable adenylate kinase measurement as a direct measure of vapour-phase
hydrogen peroxide bio-decontamination performance, expressed in terms of log
reduction. Because thermostable adenylate kinase measurement can be achieved
within a few minutes of vapour-phase hydrogen peroxide cycle completion, compared
with a minimum of 7 days for the evaluation of biological indicator growth, this
offers a potentially valuable tool for rapid vapour-phase hydrogen peroxide bio
decontamination cycle development and subsequent re-qualification.LAY ABSTRACT:
Pharmaceutical product manufacture is performed in controlled cleanroom and
closed chamber environments (isolators) to reduce the risk of contamination.
These environments undergo regular decontamination to control microbial
contamination levels, using a range of methods, one of which is to vaporize
hydrogen peroxide (a chemical disinfectant) into a gas or an aerosol and disperse
it throughout the environment, killing any microorganisms present. Biological
indicators, which consist of a small steel coupon carrying a population of
bacterial spores that are more resistant to hydrogen peroxide than are most
microorganisms, are placed within the environment, and then tested for growth
following treatment to ensure the process was effective. Confirmation of
growth/no growth (and therefore hydrogen peroxide cycle efficacy) can take up to
7 days, which significantly increases time and cost of developing and confirming
cycle efficacy. This study tests whether a new technology which uses a robust
enzyme, thermostable adenylate kinase, could be used to predict biological
indicator growth. The study shows this method can be used to confirm hydrogen
peroxide cycle efficacy, by predicting whether the BI is killed at a specific
time point or not and results are obtained in a few minutes rather than 7 days.
This potentially offers significant time and cost benefits.
PMID- 28512178
TI - Particulate Generation Mechanisms during Bulk Filling and Mitigation via New
Glass Vial.
AB - Contamination with foreign particulate matter continues to be a leading cause of
parenteral drug recalls, despite extensive control and inspection during
manufacturing. Glass is a significant source of particulate matter contamination;
however, the mechanism, source, and quantification have not been extensively
analyzed. Quantification of particulate matter generation with lab simulations
suggests that glass-to-glass contact on the filling line produces large
quantities of glass particles of various sizes. A new strengthened glass vial
with a low coefficient of friction surface is proposed to address this root cause
of glass particle generation. Lab simulations and two line trials using this new
vial demonstrated a substantial reduction of glass particulate generation, of
resulting product contamination, as well as of the frequency of required filling
line interventions. These results suggest that substantial reductions in
particulate matter contamination of all types, glass and non-glass, can be
achieved through the use of a new glass vial designed to effectively eliminate a
root cause of glass particle generation.LAY ABSTRACT: Contamination with foreign
particulate contamination continues to be a leading cause of injectable drug
recalls, despite extensive control and inspection during manufacturing. Glass
particles are one of the most common types of particulate identified; however,
the generation mechanism has not been extensively studied. Lab simulations
suggest that routine glass-to-glass contact of vials during the filling process
results in large quantities of glass particulate. A new, strengthened glass vial
with a low coefficient of friction surface is proposed to address this mechanism.
Lab simulations and multiple filling line trials demonstrated a substantial
reduction of glass particulate matter generation and product contamination with
use of the new vial. These results suggest that this new vial reduces
contamination risk by eliminating a root cause of glass particulate generation.
PMID- 28512181
TI - Inner Workings: In search for "magic" nuclei, theory catches up to experiments.
PMID- 28512183
TI - Measles outbreak in Somali American community follows anti-vaccine talks.
PMID- 28512179
TI - Cooperative Regulatory Functions of miR858 and MYB83 during Cyst Nematode
Parasitism.
AB - MicroRNAs (miRNAs) recently have been established as key regulators of
transcriptome reprogramming that define cell function and identity. Nevertheless,
the molecular functions of the greatest number of miRNA genes remain to be
determined. Here, we report cooperative regulatory functions of miR858 and its
MYB83 transcription factor target gene in transcriptome reprogramming during
Heterodera cyst nematode parasitism of Arabidopsis (Arabidopsis thaliana). Gene
expression analyses and promoter-GUS fusion assays documented a role of miR858 in
posttranscriptional regulation of MYB83 in the Heterodera schachtii-induced
feeding sites, the syncytia. Constitutive overexpression of miR858 interfered
with H. schachtii parasitism of Arabidopsis, leading to reduced susceptibility,
while reduced miR858 abundance enhanced plant susceptibility. Similarly, MYB83
expression increases were conducive to nematode infection because overexpression
of a noncleavable coding sequence of MYB83 significantly increased plant
susceptibility, whereas a myb83 mutation rendered the plants less susceptible. In
addition, RNA-seq analysis revealed that genes involved in hormone signaling
pathways, defense response, glucosinolate biosynthesis, cell wall modification,
sugar transport, and transcriptional control are the key etiological factors by
which MYB83 facilitates nematode parasitism of Arabidopsis. Furthermore, we
discovered that miR858-mediated silencing of MYB83 is tightly regulated through a
feedback loop that might contribute to fine-tuning the expression of more than a
thousand of MYB83-regulated genes in the H. schachtii-induced syncytium.
Together, our results suggest a role of the miR858-MYB83 regulatory system in
finely balancing gene expression patterns during H. schachtii parasitism of
Arabidopsis to ensure optimal cellular function.
PMID- 28512184
TI - Effect of Intensive Blood Pressure Lowering on Left Ventricular Hypertrophy in
Patients With Hypertension: SPRINT (Systolic Blood Pressure Intervention Trial).
AB - BACKGROUND: It is currently unknown whether intensive blood pressure (BP)
lowering beyond that recommended would lead to more lowering of the risk of left
ventricular hypertrophy (LVH) in patients with hypertension and whether reducing
the risk of LVH explains the reported cardiovascular disease (CVD) benefits of
intensive BP lowering in this population. METHODS: This analysis included 8164
participants (mean age, 67.9 years; 35.3% women; 31.2% blacks) with hypertension
but no diabetes mellitus from the SPRINT trial (Systolic Blood Pressure
Intervention Trial): 4086 randomly assigned to intensive BP lowering (target SBP
<120 mm Hg) and 4078 assigned to standard BP lowering (target SBP <140 mm Hg).
Progression and regression of LVH as defined by Cornell voltage criteria derived
from standard 12-lead ECGs recorded at baseline and biannually were compared
between treatment arms during a median follow-up of 3.81 years. The effect of
intensive (versus standard) BP lowering on the SPRINT primary CVD outcome (a
composite of myocardial infarction, acute coronary syndrome, stroke, heart
failure, and CVD death) was compared before and after adjustment for LVH as a
time-varying covariate. RESULTS: Among SPRINT participants without baseline LVH
(n=7559), intensive (versus standard) BP lowering was associated with a 46% lower
risk of developing LVH (hazard ratio=0.54; 95% confidence interval, 0.43-0.68).
Similarly, among SPRINT participants with baseline LVH (n=605, 7.4%), those
assigned to the intensive (versus standard) BP lowering were 66% more likely to
regress/improve their LVH (hazard ratio=1.66; 95% confidence interval, 1.31
2.11). Adjustment for LVH as a time-varying covariate did not substantially
attenuate the effect of intensive BP therapy on CVD events (hazard ratio of
intensive versus standard BP lowering on CVD, 0.76 [95% confidence interval, 0.64
0.90] and 0.77 [95% confidence interval, 0.65-0.91] before and after adjustment
for LVH as a time-varying covariate, respectively). CONCLUSIONS: Among patients
with hypertension but no diabetes mellitus, intensive BP lowering (target
systolic BP <120 mm Hg) compared with standard BP lowering (target systolic BP
<140 mm Hg) resulted in lower rates of developing new LVH in those without LVH
and higher rates of regression of LVH in those with existing LVH. This favorable
effect on LVH did not explain most of the reduction in CVD events associated with
intensive BP lowering in the SPRINT trial. CLINICAL TRIAL REGISTRATION: URL:
http://www.clinicaltrials.gov. Unique identifier: NCT01206062.
PMID- 28512186
TI - Building Ultra-High-Density Linkage Maps Based on Efficient Filtering of
Trustable Markers.
AB - The study is focused on addressing the problem of building genetic maps in the
presence of ~103-104 of markers per chromosome. We consider a spectrum of
situations with intrachromosomal heterogeneity of recombination rate, different
level of genotyping errors, and missing data. In the ideal scenario of the
absence of errors and missing data, the majority of markers should appear as
groups of cosegregating markers ("twins") representing no challenge for map
construction. The central aspect of the proposed approach is to take into account
the structure of the marker space, where each twin group (TG) and singleton
markers are represented as points of this space. The confounding effect of
genotyping errors and missing data leads to reduction of TG size, but upon a low
level of these effects surviving TGs can still be used as a source of reliable
skeletal markers. Increase in the level of confounding effects results in a
considerable decrease in the number or even disappearance of usable TGs and,
correspondingly, of skeletal markers. Here, we show that the paucity of
informative markers can be compensated by detecting kernels of markers in the
marker space using a clustering procedure, and demonstrate the utility of this
approach for high-density genetic map construction on simulated and
experimentally obtained genotyping datasets.
PMID- 28512185
TI - Cap-n-Collar Promotes Tissue Regeneration by Regulating ROS and JNK Signaling in
the Drosophila melanogaster Wing Imaginal Disc.
AB - Regeneration is a complex process that requires an organism to recognize and
repair tissue damage, as well as grow and pattern new tissue. Here, we describe a
genetic screen to identify novel regulators of regeneration. We ablated the
Drosophila melanogaster larval wing primordium by inducing apoptosis in a
spatially and temporally controlled manner and allowed the tissue to regenerate
and repattern. To identify genes that regulate regeneration, we carried out a
dominant-modifier screen by assessing the amount and quality of regeneration in
adult wings heterozygous for isogenic deficiencies. We have identified 31 regions
on the right arm of the third chromosome that modify the regenerative response.
Interestingly, we observed several distinct phenotypes: mutants that regenerated
poorly, mutants that regenerated faster or better than wild-type, and mutants
that regenerated imperfectly and had patterning defects. We mapped one deficiency
region to cap-n-collar (cnc), the Drosophila Nrf2 ortholog, which is required for
regeneration. Cnc regulates reactive oxygen species levels in the regenerating
epithelium, and affects c-Jun N-terminal protein kinase (JNK) signaling, growth,
debris localization, and pupariation timing. Here, we present the results of our
screen and propose a model wherein Cnc regulates regeneration by maintaining an
optimal level of reactive oxygen species to promote JNK signaling.
PMID- 28512188
TI - The functional movement test 9+ is a poor screening test for lower extremity
injuries in professional male football players: a 2-year prospective cohort
study.
AB - BACKGROUND: The 9+ screening battery test consists of 11 tests to assess
limitations in functional movement. AIM: To examine the association of the 9+
with lower extremity injuries and to identify a cut-off point to predict injury
risk. METHODS: Professional male football players in Qatar from 14 teams
completed the 9+ at the beginning of the 2013/2014 and 2014/2015 seasons. Time
loss injuries and exposure in training and matches were registered prospectively
by club medical staff during these seasons. Univariate and multivariate Cox
regression analyses were used to calculate HR and 95% CI. Receiver operating
characteristic (ROC) curves were calculated to determine sensitivity and
specificity and identify the optimal cut-off point for risk assessment. RESULTS:
362 players completed the 9+ and had injury and exposure registration. There were
526 injuries among 203 players (56.1%) during the two seasons; injuries to the
thigh were the most frequent. There was no association between 9+ total score and
the risk of lower extremity injuries (HR 1.02, 95% CI 0.99 to 1.05, p=0.13), even
after adjusting for other risk factors in a multivariate analysis (HR 1.01, 95%
CI 0.98 to 1.04, p=0.37). ROC curve analysis revealed an area under the curve of
0.48, and there was no cut-off point that distinguished injured from non-injured
players. CONCLUSION: The 9+ was not associated with lower extremity injury, and
it was no better than chance for distinguishing between injured and uninjured
players. Therefore, the 9+ test cannot be recommended as an injury prediction
tool in this population.
PMID- 28512187
TI - Neutral Competition for Drosophila Follicle and Cyst Stem Cell Niches Requires
Vesicle Trafficking Genes.
AB - The process of selecting for cellular fitness through competition plays a
critical role in both development and disease. The germarium, a structure at the
tip of the ovariole of a Drosophila ovary, contains two follicle stem cells
(FSCs) that undergo neutral competition for the stem cell niche. Using the FSCs
as a model, we performed a genetic screen through a collection of 126 mutants in
essential genes on the X chromosome to identify candidates that increase or
decrease competition for the FSC niche. We identified ~55 and 6% of the mutations
screened as putative FSC hypo- or hyper-competitors, respectively. We found that
a large majority of mutations in vesicle trafficking genes (11 out of the 13 in
the collection of mutants) are candidate hypo-competition alleles, and we
confirmed the hypo-competition phenotype for four of these alleles. We also show
that Sec16 and another COPII vesicle trafficking component, Sar1, are required
for follicle cell differentiation. Lastly, we demonstrate that, although some
components of vesicle trafficking are also required for neutral competition in
the cyst stem cells of the testis, there are important tissue-specific
differences. Our results demonstrate a critical role for vesicle trafficking in
stem cell niche competition and differentiation, and we identify a number of
putative candidates for further exploration.
PMID- 28512189
TI - When is a study result important for athletes, clinicians and team coaches/staff?
PMID- 28512191
TI - MiR-2392 suppresses metastasis and epithelial-mesenchymal transition by targeting
MAML3 and WHSC1 in gastric cancer.
AB - MicroRNAs have emerged as essential regulators of various cellular processes. We
identified the role and underlying mechanisms of miR-2392 in gastric cancer (GC)
metastasis. MiR-2392 was down-regulated in GC cell lines and tissues, and
overexpression of miR-2392 significantly inhibited GC invasion and metastasis in
vitro and in vivo We identified MAML3 and WHSC1 as novel targets of miR-2392, and
knockdown of MAML3 and WHSC1 had the same antimetastatic effect as that of miR
2392 in GC cells. These effects were clinically relevant, as low miR-2392
expression was correlated with high MAML3 and WHSC1 expression and poor survival
in patients with GC. Furthermore, forced expression of miR-2392 substantially
suppressed Slug and Twist1, transcriptional repressors of E-cadherin, by
targeting MAML3 and WHSC1, respectively, resulting in inhibition of the
epithelial-mesenchymal transition. These findings indicate that the miR-2392
MAML3/WHSC1-Slug/Twist1 regulatory axis plays a critical role in GC metastasis.
Restoration of miR-2392 may be a therapeutic approach for blocking GC metastasis.
Li, J., Li, T., Lu, Y., Shen, G., Guo, H., Wu, J., Lei, C., Du, F., Zhou, F.,
Zhao, X., Nie, Y., Fan, D. MiR-2392 suppresses metastasis and epithelial
mesenchymal transition by targeting MAML3 and WHSC1 in gastric cancer.
PMID- 28512190
TI - Hematopoietic origin of Langerhans cell histiocytosis and Erdheim-Chester disease
in adults.
AB - Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) are rare
histiocytic disorders induced by somatic mutation of MAPK pathway genes.
BRAFV600E mutation is the most common mutation in both conditions and also occurs
in the hematopoietic neoplasm hairy cell leukemia (HCL). It is not known if adult
LCH or ECD arises from hematopoietic stem cells (HSCs), nor which potential blood
borne precursors lead to the formation of histiocytic lesions. In this study,
BRAFV600E allele-specific polymerase chain reaction was used to map the
neoplastic clone in 20 adults with LCH, ECD, and HCL. BRAFV600E was tracked to
classical monocytes, nonclassical monocytes, and CD1c+ myeloid dendritic cells
(DCs) in the blood, and mutations were observed in HSCs and myeloid progenitors
in the bone marrow of 4 patients. The pattern of involvement of peripheral blood
myeloid cells was indistinguishable between LCH and ECD, although the histiocytic
disorders were distinct to HCL. As reported in children, detection of BRAFV600E
in peripheral blood of adults was a marker of active multisystem LCH. The healthy
counterparts of myeloid cells affected by BRAF mutation had a range of
differentiation potentials depending on exogenous signals. CD1c+ DCs acquired
high langerin and CD1a with granulocyte-macrophage colony-stimulating factor and
transforming growth factor beta alone, whereas CD14+ classical monocytes required
additional notch ligation. Both classical and nonclassical monocytes, but not
CD1c+ DCs, made foamy macrophages easily in vitro with macrophage colony
stimulating factor and human serum. These studies are consistent with a
hematopoietic origin and >1 immediate cellular precursor in both LCH and ECD.
PMID- 28512192
TI - Human mismatch repair system balances mutation rates between strands by removing
more mismatches from the lagging strand.
AB - Mismatch repair (MMR) is one of the main systems maintaining fidelity of
replication. Differences in correction of errors produced during replication of
the leading and the lagging DNA strands were reported in yeast and in human
cancers, but the causes of these differences remain unclear. Here, we analyze
data on human cancers with somatic mutations in two of the major DNA polymerases,
delta and epsilon, that replicate the genome. We show that these cancers
demonstrate a substantial asymmetry of the mutations between the leading and the
lagging strands. The direction of this asymmetry is the opposite between cancers
with mutated polymerases delta and epsilon, consistent with the role of these
polymerases in replication of the lagging and the leading strands in human cells,
respectively. Moreover, the direction of strand asymmetry observed in cancers
with mutated polymerase delta is similar to that observed in MMR-deficient
cancers. Together, these data indicate that polymerase delta (possibly together
with polymerase alpha) contributes more mismatches during replication than its
leading-strand counterpart, polymerase epsilon; that most of these mismatches are
repaired by the MMR system; and that MMR repairs about three times more
mismatches produced in cells during lagging strand replication compared with the
leading strand.
PMID- 28512195
TI - An interview with Eric Wieschaus.
AB - Eric Wieschaus is a HHMI Investigator, and the Squibb Professor in Molecular
Biology at Princeton University and the Lewis-Sigler Institute for Integrative
Genomics. In 1995, he was awarded the Nobel Prize jointly with Edward Lewis and
Christiane Nusslein-Volhard for discoveries about the genetic control of
Drosophila embryogenesis. We caught up with Eric at the joint meeting of the
German and Japanese Societies of Developmental Biologists held in Kiel in March
2017, and discussed his career, his thoughts on the field and the impact the
Nobel award had on his life.
PMID- 28512193
TI - DNA replication timing during development anticipates transcriptional programs
and parallels enhancer activation.
AB - In dividing cells, DNA replication occurs in a precise order, but many questions
remain regarding the mechanisms of replication timing establishment and
regulation. We now have generated genome-wide, high-resolution replication timing
maps throughout zebrafish development. Unexpectedly, in the rapid cell cycles
preceding the midblastula transition, a defined timing program was present that
predicted the initial wave of zygotic transcription. Replication timing was
thereafter progressively and continuously remodeled across the majority of the
genome, and epigenetic changes involved in enhancer activation frequently
paralleled developmental changes in replication timing. The long arm of
Chromosome 4 underwent a dramatic developmentally regulated switch to late
replication during gastrulation, reminiscent of mammalian X Chromosome
inactivation. This study reveals that replication timing is dynamic and tightly
linked to epigenetic and transcriptional changes throughout early zebrafish
development. These data provide insight into the regulation and functions of
replication timing and will enable further mechanistic studies.
PMID- 28512196
TI - The developmental biology of genetic Notch disorders.
AB - Notch signaling regulates a vast array of crucial developmental processes. It is
therefore not surprising that mutations in genes encoding Notch receptors or
ligands lead to a variety of congenital disorders in humans. For example, loss of
function of Notch results in Adams-Oliver syndrome, Alagille syndrome,
spondylocostal dysostosis and congenital heart disorders, while Notch gain of
function results in Hajdu-Cheney syndrome, serpentine fibula polycystic kidney
syndrome, infantile myofibromatosis and lateral meningocele syndrome.
Furthermore, structure-abrogating mutations in NOTCH3 result in CADASIL. Here, we
discuss these human congenital disorders in the context of known roles for Notch
signaling during development. Drawing on recent analyses by the exome aggregation
consortium (EXAC) and on recent studies of Notch signaling in model organisms, we
further highlight additional Notch receptors or ligands that are likely to be
involved in human genetic diseases.
PMID- 28512194
TI - Ancient antagonism between CELF and RBFOX families tunes mRNA splicing outcomes.
AB - Over 95% of human multi-exon genes undergo alternative splicing, a process
important in normal development and often dysregulated in disease. We sought to
analyze the global splicing regulatory network of CELF2 in human T cells, a well
studied splicing regulator critical to T cell development and function. By
integrating high-throughput sequencing data for binding and splicing
quantification with sequence features and probabilistic splicing code models, we
find evidence of splicing antagonism between CELF2 and the RBFOX family of
splicing factors. We validate this functional antagonism through knockdown and
overexpression experiments in human cells and find CELF2 represses RBFOX2 mRNA
and protein levels. Because both families of proteins have been implicated in the
development and maintenance of neuronal, muscle, and heart tissues, we analyzed
publicly available data in these systems. Our analysis suggests global,
antagonistic coregulation of splicing by the CELF and RBFOX proteins in mouse
muscle and heart in several physiologically relevant targets, including proteins
involved in calcium signaling and members of the MEF2 family of transcription
factors. Importantly, a number of these coregulated events are aberrantly spliced
in mouse models and human patients with diseases that affect these tissues,
including heart failure, diabetes, or myotonic dystrophy. Finally, analysis of
exons regulated by ancient CELF family homologs in chicken, Drosophila, and
Caenorhabditis elegans suggests this antagonism is conserved throughout
evolution.
PMID- 28512200
TI - A new model for lineage segregation.
PMID- 28512197
TI - Interstitial fluid osmolarity modulates the action of differential tissue surface
tension in progenitor cell segregation during gastrulation.
AB - The segregation of different cell types into distinct tissues is a fundamental
process in metazoan development. Differences in cell adhesion and cortex tension
are commonly thought to drive cell sorting by regulating tissue surface tension
(TST). However, the role that differential TST plays in cell segregation within
the developing embryo is as yet unclear. Here, we have analyzed the role of
differential TST for germ layer progenitor cell segregation during zebrafish
gastrulation. Contrary to previous observations that differential TST drives germ
layer progenitor cell segregation in vitro, we show that germ layers display
indistinguishable TST within the gastrulating embryo, arguing against
differential TST driving germ layer progenitor cell segregation in vivo We
further show that the osmolarity of the interstitial fluid (IF) is an important
factor that influences germ layer TST in vivo, and that lower osmolarity of the
IF compared with standard cell culture medium can explain why germ layers display
differential TST in culture but not in vivo Finally, we show that directed
migration of mesendoderm progenitors is required for germ layer progenitor cell
segregation and germ layer formation.
PMID- 28512198
TI - Novel role of Rac-Mid1 signaling in medial cerebellar development.
AB - Rac signaling impacts a relatively large number of downstream targets; however,
few studies have established an association between Rac pathways and pathological
conditions. In the present study, we generated mice with double knockout of Rac1
and Rac3 (Atoh1-Cre;Rac1flox/flox;Rac3-/- ) in cerebellar granule neurons (CGNs).
We observed impaired tangential migration at E16.5, as well as numerous apoptotic
CGNs at the deepest layer of the external granule layer (EGL) in the medial
cerebellum of Atoh1-Cre;Rac1flox/flox;Rac3-/- mice at P8. Atoh1
Cre;Rac1flox/flox;Rac3-/- CGNs differentiated normally until expression of
p27kip1 and NeuN in the deep EGL at P5. Primary CGNs and cerebellar microexplants
from Atoh1-Cre;Rac1flox/flox;Rac3-/- mice exhibited impaired neuritogenesis,
which was more apparent in Map2-positive dendrites. Such findings suggest that
impaired tangential migration and final differentiation of CGNs have resulted in
decreased cerebellum size and agenesis of the medial internal granule layer,
respectively. Furthermore, Rac depleted/deleted cells exhibited decreased levels
of Mid1 and impaired mTORC1 signaling. Mid1 depletion in CGNs produced mild
impairments in neuritogenesis and reductions in mTORC1 signaling. Thus, a novel
Rac-signaling pathway (Rac1-Mid1-mTORC1) may be involved in medial cerebellar
development.
PMID- 28512199
TI - Dominant-negative Sox18 function inhibits dermal papilla maturation and
differentiation in all murine hair types.
AB - SOX family proteins SOX2 and SOX18 have been reported as being essential in
determining hair follicle type; however, the role they play during development
remains unclear. Here, we demonstrate that Sox18 regulates the normal
differentiation of the dermal papilla of all hair types. In guard (primary) hair
dermal condensate (DC) cells, we identified transient Sox18 in addition to SOX2
expression at E14.5, which allowed fate tracing of primary DC cells until birth.
Similarly, expression of Sox18 was detected in the DC cells of secondary hairs at
E16.5 and in tertiary hair at E18.5. Dominant-negative Sox18 mutation (opposum)
did not prevent DC formation in any hair type. However, it affected dermal
papilla differentiation, restricting hair formation especially in secondary and
tertiary hairs. This Sox18 mutation also prevented neonatal dermal cells or
dermal papilla spheres from inducing hair in regeneration assays. Microarray
expression studies identified WNT5A and TNC as potential downstream effectors of
SOX18 that are important for epidermal WNT signalling. In conclusion, SOX18 acts
as a mesenchymal molecular switch necessary for the formation and function of the
dermal papilla in all hair types.
PMID- 28512202
TI - Heat shock protein regulates human hepatocyte differentiation.
PMID- 28512201
TI - Exciting input for inhibitory neurons.
PMID- 28512203
TI - The mechanism of activation of IRAK1 and IRAK4 by interleukin-1 and Toll-like
receptor agonists.
AB - We have developed the first assays that measure the protein kinase activities of
interleukin-1 receptor-associated kinase 1 (IRAK1) and IRAK4 reliably in human
cell extracts, by employing Pellino1 as a substrate in conjunction with specific
pharmacological inhibitors of IRAK1 and IRAK4. We exploited these assays to show
that IRAK4 was constitutively active and that its intrinsic activity towards
Pellino1 was not increased significantly by stimulation with interleukin-1 (IL-1)
in IL-1R-expressing HEK293 cells, Pam3CSK4-stimulated human THP1 monocytes or
primary human macrophages. Our results, in conjunction with those of other
investigators, suggest that the IL-1-stimulated trans-autophosphorylation of
IRAK4 is initiated by the myeloid differentiation primary response gene 88
induced dimerization of IRAK4 and is not caused by an increase in the intrinsic
catalytic activity of IRAK4. In contrast with IRAK4, we found that IRAK1 was
inactive in unstimulated cells and converted into an active protein kinase in
response to IL-1 or Pam3CSK4 in human cells. Surprisingly, the IL-1-stimulated
activation of IRAK1 was not affected by pharmacological inhibition of IRAK4 and
not reversed by dephosphorylation and/or deubiquitylation, suggesting that IRAK1
catalytic activity is not triggered by a covalent modification but by an
allosteric mechanism induced by its interaction with IRAK4.
PMID- 28512206
TI - Genetic testing and reproductive choice in neurological disorders.
AB - Genetic testing is increasingly important for investigating suspected inherited
neurological conditions. A genetic diagnosis can have a huge impact on patients
and also their families. It is important for neurologists to appreciate the
presymptomatic and prenatal testing options available to patients and their at
risk relatives once a genetic disorder is diagnosed. Asymptomatic family members
can experience considerable psychological distress from the knowledge that they
might have inherited a neurodegenerative condition. They may also be concerned
about the risk of their children inheriting the condition. Information on
reproductive options can provide hope and reassurance. This paper reviews the
principles of genetic testing in neurological practice, and how they can be
applied in prenatal and preimplantation genetic diagnosis. We explain the basis
for direct and exclusion testing, use case examples to illustrate the process by
which families are counselled and discuss the ethical implications of
reproductive technologies.
PMID- 28512204
TI - The human RNA-binding protein RBFA promotes the maturation of the mitochondrial
ribosome.
AB - Accurate assembly and maturation of human mitochondrial ribosomes is essential
for synthesis of the 13 polypeptides encoded by the mitochondrial genome. This
process requires the correct integration of 80 proteins, 1 mt (mitochondrial)
tRNA and 2 mt-rRNA species, the latter being post-transcriptionally modified at
many sites. Here, we report that human ribosome-binding factor A (RBFA) is a
mitochondrial RNA-binding protein that exerts crucial roles in mitoribosome
biogenesis. Unlike its bacterial orthologue, RBFA associates mainly with helices
44 and 45 of the 12S rRNA in the mitoribosomal small subunit to promote
dimethylation of two highly conserved consecutive adenines. Characterization of
RBFA-depleted cells indicates that this dimethylation is not a prerequisite for
assembly of the small ribosomal subunit. However, the RBFA-facilitated
modification is necessary for completing mt-rRNA maturation and regulating
association of the small and large subunits to form a functional monosome
implicating RBFA in the quality control of mitoribosome formation.
PMID- 28512207
TI - 'Organic' and 'non-organic': a tale of two turnips.
PMID- 28512205
TI - Phorbol-12-myristate-13-acetate-mediated stabilization of leukemia inhibitory
factor (lif) mRNA: involvement of Nucleolin and PCBP1.
AB - Leukemia inhibitory factor (LIF) is a potent pleiotropic cytokine involved in
diverse biological activities, thereby requiring precise spatial and temporal
control of its expression. The present study reveals that enhanced expression of
LIF in response to PMA (phorbol-12-myristate-13-acetate) in human histiocytic
lymphoma cell line U937 largely happens through stabilization of its mRNA.
Functional characterization of the long 3'-untranslated region of human lif mRNA
revealed several conserved sequences with conventional cis-acting elements. A 216
nucleotide containing proximal cis-element with two AUUUA pentamers and four poly
rC sequences demonstrated significant mRNA destabilizing potential, which, on
treatment with PMA, showed stabilizing activity. Affinity chromatography followed
by western blot and RNA co-immunoprecipitation of PMA-treated U937 extract
identified Nucleolin and PCBP1 as two protein trans-factors interacting with lif
mRNA, specifically to the proximal non-conventional AU-rich region. PMA induced
nucleo-cytoplasmic translocation of both Nucleolin and PCBP1. RNA-dependent in
vivo co-association of both these proteins with lif mRNA was demonstrated by
decreased co-precipitation in the presence of RNase. Ectopic overexpression of
Nucleolin showed stabilization of both intrinsic lif mRNA and gfp reporter,
whereas knockdown of Nucleolin and PCBP1 demonstrated a significant decrease in
both lif mRNA and protein levels. Collectively, this report establishes the
stabilization of lif mRNA by PMA, mediated by the interactions of two RNA-binding
proteins, Nucleolin and PCBP1 with a proximal cis-element.
PMID- 28512208
TI - Chorioretinitis: a potential clue to the early diagnosis of subacute sclerosing
panencephalitis.
AB - We describe a 36-year-old man with subacute sclerosing panencephalitis (SSPE)
presenting with chorioretinitis two years before onset of other neurological
features. He had neither myoclonus nor the typical EEG features of SSPE. The
diagnosis was confirmed in the appropriate clinical setting by detecting elevated
measles antibody titres in cerebrospinal fluid and serum. Clinicians should
consider SSPE among the differential diagnoses in chorioretinitis. This is
particularly so if there is macular or perimacular involvement with concurrent
involvement of the optic nerve in young patients, even without other
characteristic neurological symptoms.
PMID- 28512209
TI - Venous hypertensive encephalopathy secondary to venous sinus thrombosis and dural
arteriovenous fistula.
AB - A 52-year-old man with a history of factor V Leiden thrombophilia, persistent
headaches and papilloedema presented with worsening vision and confusion. MRI and
MR angiography of the brain at the time of this presentation showed findings
concerning for transverse sinus thrombosis and an associated dural arteriovenous
fistula. Dural venous sinus thrombosis can lead to the formation of a dural
arteriovenous fistula, which must be considered in the differential diagnosis for
intracranial hypertension in patients with thrombophilia.
PMID- 28512210
TI - Margaret McCartney: The NHS needs big, firm IT pants.
PMID- 28512211
TI - Correction for Bernard et al., "Splicing Factor Spf30 Assists Exosome-Mediated
Gene Silencing in Fission Yeast".
PMID- 28512212
TI - Correction for Khalimonchuk et al., "Formation of the Redox Cofactor Centers
during Cox1 Maturation in Yeast Cytochrome Oxidase".
PMID- 28512213
TI - Retraction for Roy et al., "DDB2, an Essential Mediator of Premature Senescence".
PMID- 28512214
TI - Correction for Munoz-Galvan et al., "Distinct Roles of Mus81, Yen1, Slx1-Slx4,
and Rad1 Nucleases in the Repair of Replication-Born Double-Strand Breaks by
Sister Chromatid Exchange".
PMID- 28512216
TI - Setting the (Scientific) Record Straight: Molecular and Cellular Biology Responds
to Postpublication Review.
PMID- 28512217
TI - Loss of the homologous recombination gene rad51 leads to Fanconi anemia-like
symptoms in zebrafish.
AB - RAD51 is an indispensable homologous recombination protein, necessary for strand
invasion and crossing over. It has recently been designated as a Fanconi anemia
(FA) gene, following the discovery of two patients carrying dominant-negative
mutations. FA is a hereditary DNA-repair disorder characterized by various
congenital abnormalities, progressive bone marrow failure, and cancer
predisposition. In this report, we describe a viable vertebrate model of RAD51
loss. Zebrafish rad51 loss-of-function mutants developed key features of FA,
including hypocellular kidney marrow, sensitivity to cross-linking agents, and
decreased size. We show that some of these symptoms stem from both decreased
proliferation and increased apoptosis of embryonic hematopoietic stem and
progenitor cells. Comutation of p53 was able to rescue the hematopoietic defects
seen in the single mutants, but led to tumor development. We further demonstrate
that prolonged inflammatory stress can exacerbate the hematological impairment,
leading to an additional decrease in kidney marrow cell numbers. These findings
strengthen the assignment of RAD51 as a Fanconi gene and provide more evidence
for the notion that aberrant p53 signaling during embryogenesis leads to the
hematological defects seen later in life in FA. Further research on this
zebrafish FA model will lead to a deeper understanding of the molecular basis of
bone marrow failure in FA and the cellular role of RAD51.
PMID- 28512219
TI - Energetic cost of building a virus.
AB - Viruses are incapable of autonomous energy production. Although many experimental
studies make it clear that viruses are parasitic entities that hijack the
molecular resources of the host, a detailed estimate for the energetic cost of
viral synthesis is largely lacking. To quantify the energetic cost of viruses to
their hosts, we enumerated the costs associated with two very distinct but
representative DNA and RNA viruses, namely, T4 and influenza. We found that, for
these viruses, translation of viral proteins is the most energetically expensive
process. Interestingly, the costs of building a T4 phage and a single influenza
virus are nearly the same. Due to influenza's higher burst size, however, the
overall cost of a T4 phage infection is only 2-3% of the cost of an influenza
infection. The costs of these infections relative to their host's estimated
energy budget during the infection reveal that a T4 infection consumes about a
third of its host's energy budget, whereas an influenza infection consumes only ~
1%. Building on our estimates for T4, we show how the energetic costs of double
stranded DNA phages scale with the capsid size, revealing that the dominant cost
of building a virus can switch from translation to genome replication above a
critical size. Last, using our predictions for the energetic cost of viruses, we
provide estimates for the strengths of selection and genetic drift acting on
newly incorporated genetic elements in viral genomes, under conditions of energy
limitation.
PMID- 28512221
TI - Shear bands as manifestation of a criticality in yielding amorphous solids.
AB - Amorphous solids increase their stress as a function of an applied strain until a
mechanical yield point whereupon the stress cannot increase anymore, afterward
exhibiting a steady state with a constant mean stress. In stress-controlled
experiments, the system simply breaks when pushed beyond this mean stress. The
ubiquity of this phenomenon over a huge variety of amorphous solids calls for a
generic theory that is free of microscopic details. Here, we offer such a theory:
The mechanical yield is a thermodynamic phase transition, where yield occurs as a
spinodal phenomenon. At the spinodal point, there exists a divergent correlation
length that is associated with the system-spanning instabilities (also known as
shear bands), which are typical to the mechanical yield. The theory, the order
parameter used, and the correlation functions that exhibit the divergent
correlation length are universal in nature and can be applied to any amorphous
solids that undergo mechanical yield.
PMID- 28512218
TI - Ubiquitin- and ATP-dependent unfoldase activity of P97/VCP*NPLOC4*UFD1L is
enhanced by a mutation that causes multisystem proteinopathy.
AB - p97 is a "segregase" that plays a key role in numerous ubiquitin (Ub)-dependent
pathways such as ER-associated degradation. It has been hypothesized that p97
extracts proteins from membranes or macromolecular complexes to enable their
proteasomal degradation; however, the complex nature of p97 substrates has made
it difficult to directly observe the fundamental basis for this activity. To
address this issue, we developed a soluble p97 substrate-Ub-GFP modified with K48
linked ubiquitin chains-for in vitro p97 activity assays. We demonstrate that WT
p97 can unfold proteins and that this activity is dependent on the p97 adaptor
NPLOC4-UFD1L, ATP hydrolysis, and substrate ubiquitination, with branched chains
providing maximal stimulation. Furthermore, we show that a p97 mutant that causes
inclusion body myopathy, Paget's disease of bone, and frontotemporal dementia in
humans unfolds substrate faster, suggesting that excess activity may underlie
pathogenesis. This work overcomes a significant barrier in the study of p97 and
will allow the future dissection of p97 mechanism at a level of detail previously
unattainable.
PMID- 28512220
TI - Increasing intracellular magnesium levels with the 31-amino acid MgtS protein.
AB - Synthesis of the 31-amino acid, inner membrane protein MgtS (formerly denoted
YneM) is induced by very low Mg2+ in a PhoPQ-dependent manner in Escherichia coli
Here we report that MgtS acts to increase intracellular Mg2+ levels and maintain
cell integrity upon Mg2+ depletion. Upon development of a functional tagged
derivative of MgtS, we found that MgtS interacts with MgtA to increase the levels
of this P-type ATPase Mg2+ transporter under Mg2+-limiting conditions.
Correspondingly, the effects of MgtS upon Mg2+ limitation are lost in a ?mgtA
mutant, and MgtA overexpression can suppress the ?mgtS phenotype. MgtS
stabilization of MgtA provides an additional layer of regulation of this tightly
controlled Mg2+ transporter and adds to the list of small proteins that regulate
inner membrane transporters.
PMID- 28512222
TI - Looplessness in networks is linked to trophic coherence.
AB - Many natural, complex systems are remarkably stable thanks to an absence of
feedback acting on their elements. When described as networks these exhibit few
or no cycles, and associated matrices have small leading eigenvalues. It has been
suggested that this architecture can confer advantages to the system as a whole,
such as "qualitative stability," but this observation does not in itself explain
how a loopless structure might arise. We show here that the number of feedback
loops in a network, as well as the eigenvalues of associated matrices, is
determined by a structural property called trophic coherence, a measure of how
neatly nodes fall into distinct levels. Our theory correctly classifies a variety
of networks-including those derived from genes, metabolites, species, neurons,
words, computers, and trading nations-into two distinct regimes of high and low
feedback and provides a null model to gauge the significance of related
magnitudes. Because trophic coherence suppresses feedback, whereas an absence of
feedback alone does not lead to coherence, our work suggests that the reasons for
"looplessness" in nature should be sought in coherence-inducing mechanisms.
PMID- 28512223
TI - Kinematics of the lever arm swing in myosin VI.
AB - Myosin VI (MVI) is the only known member of the myosin superfamily that, upon
dimerization, walks processively toward the pointed end of the actin filament.
The leading head of the dimer directs the trailing head forward with a power
stroke, a conformational change of the motor domain exaggerated by the lever arm.
Using a unique coarse-grained model for the power stroke of a single MVI, we
provide the molecular basis for its motility. We show that the power stroke
occurs in two major steps. First, the motor domain attains the poststroke
conformation without directing the lever arm forward; and second, the lever arm
reaches the poststroke orientation by undergoing a rotational diffusion. From the
analysis of the trajectories, we discover that the potential that directs the
rotating lever arm toward the poststroke conformation is almost flat, implying
that the lever arm rotation is mostly uncoupled from the motor domain. Because a
backward load comparable to the largest interhead tension in a MVI dimer prevents
the rotation of the lever arm, our model suggests that the leading-head lever arm
of a MVI dimer is uncoupled, in accord with the inference drawn from polarized
total internal reflection fluorescence (polTIRF) experiments. Without any
adjustable parameter, our simulations lead to quantitative agreement with polTIRF
experiments, which validates the structural insights. Finally, in addition to
making testable predictions, we also discuss the implications of our model in
explaining the broad step-size distribution of the MVI stepping pattern.
PMID- 28512224
TI - The general form of Hamilton's rule makes no predictions and cannot be tested
empirically.
AB - Hamilton's rule asserts that a trait is favored by natural selection if the
benefit to others, [Formula: see text], multiplied by relatedness, [Formula: see
text], exceeds the cost to self, [Formula: see text] Specifically, Hamilton's
rule states that the change in average trait value in a population is
proportional to [Formula: see text] This rule is commonly believed to be a
natural law making important predictions in biology, and its influence has spread
from evolutionary biology to other fields including the social sciences. Whereas
many feel that Hamilton's rule provides valuable intuition, there is disagreement
even among experts as to how the quantities [Formula: see text], [Formula: see
text], and [Formula: see text] should be defined for a given system. Here, we
investigate a widely endorsed formulation of Hamilton's rule, which is said to be
as general as natural selection itself. We show that, in this formulation,
Hamilton's rule does not make predictions and cannot be tested empirically. It
turns out that the parameters [Formula: see text] and [Formula: see text] depend
on the change in average trait value and therefore cannot predict that change. In
this formulation, which has been called "exact and general" by its proponents,
Hamilton's rule can "predict" only the data that have already been given.
PMID- 28512225
TI - High Arctic Holocene temperature record from the Agassiz ice cap and Greenland
ice sheet evolution.
AB - We present a revised and extended high Arctic air temperature reconstruction from
a single proxy that spans the past ~12,000 y (up to 2009 CE). Our reconstruction
from the Agassiz ice cap (Ellesmere Island, Canada) indicates an earlier and
warmer Holocene thermal maximum with early Holocene temperatures that are 4-5
degrees C warmer compared with a previous reconstruction, and regularly exceed
contemporary values for a period of ~3,000 y. Our results show that air
temperatures in this region are now at their warmest in the past 6,800-7,800 y,
and that the recent rate of temperature change is unprecedented over the entire
Holocene. The warmer early Holocene inferred from the Agassiz ice core leads to
an estimated ~1 km of ice thinning in northwest Greenland during the early
Holocene using the Camp Century ice core. Ice modeling results show that this
large thinning is consistent with our air temperature reconstruction. The
modeling results also demonstrate the broader significance of the enhanced
warming, with a retreat of the northern ice margin behind its present position in
the mid Holocene and a ~25% increase in total Greenland ice sheet mass loss (~1.4
m sea-level equivalent) during the last deglaciation, both of which have
implications for interpreting geodetic measurements of land uplift and gravity
changes in northern Greenland.
PMID- 28512226
TI - Reply to Padmanabhan and Dixit: Hepatitis C virus entry inhibitors for optimally
boosting direct-acting antiviral-based treatments.
PMID- 28512227
TI - Reply to Candel et al.: Evidence for evolutionary conservation of folding
kinetics in the thioredoxin protein family.
PMID- 28512228
TI - Fast folding and slow unfolding of a resurrected Precambrian protein.
PMID- 28512229
TI - Inhibitors of hepatitis C virus entry may be potent ingredients of optimal drug
combinations.
PMID- 28512231
TI - Survey on antimicrobial prescribing patterns in small animal veterinary practice
in Emilia Romagna, Italy.
AB - This investigation provides for the first time a general view of the prescribing
patterns ofantimicrobials in small animal practice in Emilia Romagna, Italy. In
the context of a projecton antimicrobial resistance managed by the Regional
Veterinary Service, veterinary clinicianswere invited to voluntarily complete an
online questionnaire. This was designed to gatherinformation on antimicrobial
prescribing practices and biosecurity measures and tounderstand the perception of
the issue specific to this region of Italy. In total, 266questionnaires correctly
completed were collected. Although clinicians seemed to followdifferent
approaches when using antimicrobials, the data analysis revealed a
generalawareness on resistance. Penicillins were the most commonly prescribed
class, followed by(fluoro)quinolones and cephalosporins. Among those who use
laboratory testing more orless frequently (microbiological analysis and
susceptibility testing) to support theirprescribing habits, only 7 per cent make
a habit of always waiting for the results beforestarting the treatment. Seventy
eight per cent of the respondents declared the use ofantimicrobials licensed for
human beings. Biosecurity measures were carefully taken intoaccount by the
majority of the veterinarians. The results identified the antimicrobial
classesthat are commonly prescribed and highlighted that perioperative hygiene
measures and theuse of laboratory diagnosis are critical aspects that need to be
emphasised in drawing upguidelines on the prudent use of these drugs in pets.
PMID- 28512232
TI - Loop-mediated isothermal amplification for extended spectrum beta-lactamase gene
detection in poultry carcase.
PMID- 28512233
TI - Identification, assessment and management of new and re-emerging animal-related
risks: UK perspective.
AB - Veterinary surveillance programmes aim to reduce the burden to the public,
livestock andwider society posed by animal-related 'risks' (referred to as
'threats' later in the paper inline with a definition used by the European Food
Safety Authority) including the reemergenceof diseases believed absent or
eradicated. To achieve this, it is important to havea systematic approach to
identifying and dealing with such threats rapidly and effectively.This paper
describes the transparent, systematic and auditable process used for
identifying,assessing, escalating and prioritising new and re-emerging animal
related threats in the UK.This has been achieved through the establishment of a
Veterinary Risk Group in late 2009.
PMID- 28512230
TI - Differential Proteomic Analysis of Gender-dependent Hepatic Tumorigenesis in
Hras12V Transgenic Mice.
AB - Male prevalence is an outstanding characteristic of hepatocellular carcinoma
(HCC), and the underlying mechanisms for this have remained largely unknown. In
the present study, Hras12V transgenic mice, in which hepatocyte-specific
expression of the ras oncogene induces male-biased hepatic tumorigenesis, were
studied, and altered proteins were detected by two-dimensional fluorescence
difference gel electrophoresis (2D-DIGE). Protein samples from hepatic tumor
tissues (T) and peritumor tissues (P) of transgenic males and females and the
corresponding normal liver tissues (Wt) of nontransgenic males and females were
subjected to pairwise comparisons based on proteomic analysis. Among 2381
autodetected protein spots, more than 1600 were differentially expressed based on
a pairwise comparison (|ratio| > = 1.5, p < = 0.05). Of these, 180 spots were
randomly selected for matrix-assisted laser desorption ionization tandem time-of
flight mass spectrometry (MALDI-TOF/TOF MS) identification; finally, 89 distinct
proteins were obtained. Among these 89 proteins, 7 and 50 proteins were further
validated by Western blotting and literature investigation, respectively.
Intriguingly, compared with Wt, the altered proteins were relatively concentrated
in T in transgenic females but in P in transgenic males. Consistently, the levels
of p-ERK and p-mTOR were significantly higher in the T of females compared with
that of males. The pathway enrichment assay showed that 5 pathways in males but
only 1 in females were significantly altered in terms of the upregulated proteins
in T compared with Wt. These data indicate that female hepatocytes are disturbed
by oncogenes with great difficulty, whereas male hepatocytes readily do so. In
addition, 33 proteins were gender-dependently altered in hepatic tumorigenesis.
Moreover, 4% DNA packaging and 4% homeostasis-related functional proteins were
found in females but not in males, and more nucleus proteins were found in
females (8%) than in males (3%). In conclusion, the proteomic data and
comparative analysis presented here offer crucial clues for elucidating the
mechanisms that underlie the male prevalence in HCC.
PMID- 28512234
TI - A guide for targeted SUMO removal.
AB - SUMO homeostasis is important for many cellular processes. In the current issue
of Genes & Development, Liang and colleagues (pp. 802-815) demonstrate how a
desumoylation enzyme is targeted to the nucleolus for removing SUMO from specific
substrates and how curtailing sumoylation levels can regulate transcription in
this nuclear compartment.
PMID- 28512235
TI - Identifying the niche controlling melanocyte differentiation.
AB - Melanocytes present in hair follicles are responsible for their pigmentation.
Melanocyte differentiation and hair pigmentation depend on the stem cell factor
(SCF)/c-Kit signaling pathway, but the niche that regulates melanocyte
differentiation is not well characterized. In this issue of Genes & Development,
Liao and colleagues (pp. 744-756) identify Krox20+-derived cells of the hair
shaft as the niche and the essential source of SCF required for melanocyte
maturation. This study delineates the niche factors regulating melanocyte
differentiation and hair pigmentation and opens up new avenues to further
characterize the cross-talk between the hair follicle and melanocytes that
controls melanocyte maintenance and differentiation.
PMID- 28512238
TI - Corrigendum: Evolution of a transcriptional regulator from a transmembrane
nucleoporin.
PMID- 28512239
TI - Erratum: BRaf signaling principles unveiled by large-scale human mutation
analysis with a rapid lentivirus-based gene replacement method.
PMID- 28512237
TI - Regulation of DNA demethylation by the XPC DNA repair complex in somatic and
pluripotent stem cells.
AB - Faithful resetting of the epigenetic memory of a somatic cell to a pluripotent
state during cellular reprogramming requires DNA methylation to silence somatic
gene expression and dynamic DNA demethylation to activate pluripotency gene
transcription. The removal of methylated cytosines requires the base excision
repair enzyme TDG, but the mechanism by which TDG-dependent DNA demethylation
occurs in a rapid and site-specific manner remains unclear. Here we show that the
XPC DNA repair complex is a potent accelerator of global and locus-specific DNA
demethylation in somatic and pluripotent stem cells. XPC cooperates with TDG
genome-wide to stimulate the turnover of essential intermediates by overcoming
slow TDG-abasic product dissociation during active DNA demethylation. We further
establish that DNA demethylation induced by XPC expression in somatic cells
overcomes an early epigenetic barrier in cellular reprogramming and facilitates
the generation of more robust induced pluripotent stem cells, characterized by
enhanced pluripotency-associated gene expression and self-renewal capacity. Taken
together with our previous studies establishing the XPC complex as a
transcriptional coactivator, our findings underscore two distinct but
complementary mechanisms by which XPC influences gene regulation by coordinating
efficient TDG-mediated DNA demethylation along with active transcription during
somatic cell reprogramming.
PMID- 28512241
TI - Assessment of Breast Cancer Risk Factors Reveals Subtype Heterogeneity.
AB - Subtype heterogeneity for breast cancer risk factors has been suspected,
potentially reflecting etiologic differences and implicating risk prediction.
However, reports are conflicting regarding the presence of heterogeneity for many
exposures. To examine subtype heterogeneity across known breast cancer risk
factors, we conducted a case-control analysis of 2,632 breast cancers and 15,945
controls in Sweden. Molecular subtype was predicted from pathology record-derived
IHC markers by a classifier trained on PAM50 subtyping. Multinomial logistic
regression estimated separate ORs for each subtype by the exposures parity, age
at first birth, breastfeeding, menarche, hormone replacement therapy use,
somatotype at age 18, benign breast disease, mammographic density, polygenic risk
score, family history of breast cancer, and BRCA mutations. We found clear
subtype heterogeneity for genetic factors and breastfeeding. Polygenic risk score
was associated with all subtypes except for the basal-like (Pheterogeneity <
0.0001). "Never breastfeeding" was associated with increased risk of basal-like
subtype [OR 4.17; 95% confidence interval (CI) 1.89-9.21] compared with both
nulliparity (reference) and breastfeeding. Breastfeeding was not associated with
risk of HER2-overexpressing type, but protective for all other subtypes. The
observed heterogeneity in risk of distinct breast cancer subtypes for germline
variants supports heterogeneity in etiology and has implications for their use in
risk prediction. The association between basal-like subtype and breastfeeding
merits more research into potential causal mechanisms and confounders. Cancer
Res; 77(13); 3708-17. (c)2017 AACR.
PMID- 28512236
TI - Focus on cutaneous and uveal melanoma specificities.
AB - Cutaneous melanoma (CM) and uveal melanoma (UM) derive from cutaneous and uveal
melanocytes that share the same embryonic origin and display the same cellular
function. However, the etiopathogenesis and biological behaviors of these
melanomas are very different. CM and UM display distinct landscapes of genetic
alterations and show different metastatic routes and tropisms. Hence, therapeutic
improvements achieved in the last few years for the treatment of CM have failed
to ameliorate the clinical outcomes of patients with UM. The scope of this review
is to discuss the differences in tumorigenic processes (etiologic factors and
genetic alterations) and tumor biology (gene expression and signaling pathways)
between CM and UM. We develop hypotheses to explain these differences, which
might provide important clues for research avenues and the identification of
actionable vulnerabilities suitable for the development of new therapeutic
strategies for metastatic UM.
PMID- 28512240
TI - STING Activation Reverses Lymphoma-Mediated Resistance to Antibody Immunotherapy.
AB - Tumors routinely attract and co-opt macrophages to promote their growth,
angiogenesis, and metastasis. Macrophages are also the key effector cell for mAb
therapies. Here we report that the tumor microenvironment creates an
immunosuppressive signature on tumor-associated macrophages (TAM), which favors
expression of inhibitory rather than activating Fcgamma receptors (FcgammaR),
thereby limiting the efficacy of mAb immunotherapy. We assessed a panel of TLR
and STING agonists (a) for their ability to reprogram macrophages to a state
optimal for mAb immunotherapy. Both STINGa and TLRa induced cytokine release,
modulated FcgammaR expression, and augmented mAb-mediated tumor cell phagocytosis
in vitro However, only STINGa reversed the suppressive FcgammaR profile in vivo,
providing strong adjuvant effects to anti-CD20 mAb in murine models of lymphoma.
Potent adjuvants like STINGa, which can improve FcgammaR activatory:inhibitory
(A:I) ratios on TAM, are appealing candidates to reprogram TAM and curb tumor
mediated immunosuppression, thereby empowering mAb efficacy. Cancer Res; 77(13);
3619-31. (c)2017 AACR.
PMID- 28512242
TI - A Systematic Analysis of Oncogenic Gene Fusions in Primary Colon Cancer.
AB - Genomic rearrangements that give rise to oncogenic gene fusions can offer
actionable targets for cancer therapy. Here we present a systematic analysis of
oncogenic gene fusions among a clinically well-characterized, prospectively
collected set of 278 primary colon cancers spanning diverse tumor stages and
clinical outcomes. Gene fusions and somatic genetic variations were identified in
fresh frozen clinical specimens by Illumina RNA-sequencing, the STAR fusion gene
detection pipeline, and GATK RNA-seq variant calling. We considered gene fusions
to be pathogenically relevant when recurrent, producing divergent gene expression
(outlier analysis), or as functionally important (e.g., kinase fusions). Overall,
2.5% of all specimens were defined as harboring a relevant gene fusion (kinase
fusions 1.8%). Novel configurations of BRAF, NTRK3, and RET gene fusions
resulting from chromosomal translocations were identified. An R-spondin fusion
was found in only one tumor (0.35%), much less than an earlier reported frequency
of 10% in colorectal cancers. We also found a novel fusion involving USP9X-ERAS
formed by chromothripsis and leading to high expression of ERAS, a constitutively
active RAS protein normally expressed only in embryonic stem cells. This USP9X
ERAS fusion appeared highly oncogenic on the basis of its ability to activate AKT
signaling. Oncogenic fusions were identified only in lymph node-negative tumors
that lacked BRAF or KRAS mutations. In summary, we identified several novel
oncogenic gene fusions in colorectal cancer that may drive malignant development
and offer new targets for personalized therapy. Cancer Res; 77(14); 3814-22.
(c)2017 AACR.
PMID- 28512243
TI - Plk1 Phosphorylation of Mre11 Antagonizes the DNA Damage Response.
AB - The mitotic kinase Plk1 contributes to the DNA damage response (DDR) by targeting
multiple factors downstream of the core responder kinase ATM/ATR. In this study,
we show that Polo-like kinase 1 (Plk1) also phosphorylates key factors upstream
of ATM/ATR and regulates their DDR-related functions. Plk1 phosphorylated Mre11,
a component of the Mre11/Rad50/Nbs1 (MRN) complex, at serine 649 (S649) during
DDR. Phosphorylation of Mre11-S649 by Plk1 primed subsequent CK2-mediated
phosphorylation at Mre11-serine 688 (S688). Phosphorylation of Mre11 at S649/S688
inhibited loading of the MRN complex to damaged DNA, leading to both premature
DNA damage checkpoint termination and inhibition of DNA repair. Tumors expressing
phosphomimetic Mre11 were more sensitive to the PARP inhibitor olaparib, compared
with those expressing unphosphorylatable Mre11, suggesting that patients with
elevated Plk1 expression might benefit from olaparib treatment. Cancer Res;
77(12); 3169-80. (c)2017 AACR.
PMID- 28512244
TI - Engineering and Functional Characterization of Fusion Genes Identifies Novel
Oncogenic Drivers of Cancer.
AB - Oncogenic gene fusions drive many human cancers, but tools to more quickly
unravel their functional contributions are needed. Here we describe methodology
permitting fusion gene construction for functional evaluation. Using this
strategy, we engineered the known fusion oncogenes, BCR-ABL1, EML4-ALK, and ETV6
NTRK3, as well as 20 previously uncharacterized fusion genes identified in The
Cancer Genome Atlas datasets. In addition to confirming oncogenic activity of the
known fusion oncogenes engineered by our construction strategy, we validated five
novel fusion genes involving MET, NTRK2, and BRAF kinases that exhibited potent
transforming activity and conferred sensitivity to FDA-approved kinase
inhibitors. Our fusion construction strategy also enabled domain-function studies
of BRAF fusion genes. Our results confirmed other reports that the transforming
activity of BRAF fusions results from truncation-mediated loss of inhibitory
domains within the N-terminus of the BRAF protein. BRAF mutations residing within
this inhibitory region may provide a means for BRAF activation in cancer,
therefore we leveraged the modular design of our fusion gene construction
methodology to screen N-terminal domain mutations discovered in tumors that are
wild-type at the BRAF mutation hotspot, V600. We identified an oncogenic
mutation, F247L, whose expression robustly activated the MAPK pathway and
sensitized cells to BRAF and MEK inhibitors. When applied broadly, these tools
will facilitate rapid fusion gene construction for subsequent functional
characterization and translation into personalized treatment strategies. Cancer
Res; 77(13); 3502-12. (c)2017 AACR.
PMID- 28512245
TI - Merkel Cell Polyomavirus Small T Antigen Initiates Merkel Cell Carcinoma-like
Tumor Development in Mice.
AB - Merkel cell carcinoma (MCC) tumor cells express several markers detected in
normal Merkel cells, a nonproliferative population of neuroendocrine cells that
arise from epidermis. MCCs frequently contain Merkel cell polyomavirus (MCPyV)
DNA and express viral transforming antigens, sT and tLT, but the role of these
putative oncogenes in MCC development, and this tumor's cell of origin, are
unknown. Using a panel of preterm transgenic mice, we show that epidermis
targeted coexpression of sT and the cell fate-determinant atonal bHLH
transcription factor 1 (ATOH1) leads to development of widespread cellular
aggregates, with histology and marker expression mimicking that of human
intraepidermal MCC. The MCC-like tumor phenotype was dependent on the FBXW7
binding domain of sT, but not the sT-PP2A binding domain. Coexpression of MCPyV
tLT did not appreciably alter the phenotype driven by either sT or sT combined
with ATOH1. MCPyV sT, when coexpressed with ATOH1, is thus sufficient to initiate
development of epidermis-derived MCC-like tumors in mice. Cancer Res; 77(12);
3151-7. (c)2017 AACR.
PMID- 28512246
TI - Tumor-Associated Macrophages Promote Malignant Progression of Breast Phyllodes
Tumors by Inducing Myofibroblast Differentiation.
AB - Myofibroblast differentiation plays an important role in the malignant
progression of phyllodes tumor, a fast-growing neoplasm derived from periductal
stromal cells of the breast. Macrophages are frequently found in close proximity
with myofibroblasts, but it is uncertain whether they are involved in the
myofibroblast differentiation during phyllodes tumor progression. Here we show
that increased density of tumor-associated macrophage (TAM) correlates with
malignant progression of phyllodes tumor. We found that TAMs stimulated
myofibroblast differentiation and promoted the proliferation and invasion of
phyllodes tumor cells. Furthermore, we found that levels of the chemokine CCL18
in TAM was an independent prognostic factor of phyllodes tumor. Mechanistic
investigations showed that CCL18 promoted expression of alpha-smooth muscle
actin, a hallmark of myofibroblast, along with the proliferation and invasion of
phyllodes tumor cells, and that CCL18-driven myofibroblast differentiation was
mediated by an NF-kappaB/miR-21/PTEN/AKT signaling axis. In murine xenograft
models of human phyllodes tumor, CCL18 accelerated tumor growth, induced
myofibroblast differentiation, and promoted metastasis. Taken together, our
findings indicated that TAM drives myofibroblast differentiation and malignant
progression of phyllodes tumor through a CCL18-driven signaling cascade amenable
to antibody disruption. Cancer Res; 77(13); 3605-18. (c)2017 AACR.
PMID- 28512247
TI - Targetable T-type Calcium Channels Drive Glioblastoma.
AB - Glioblastoma (GBM) stem-like cells (GSC) promote tumor initiation, progression,
and therapeutic resistance. Here, we show how GSCs can be targeted by the FDA
approved drug mibefradil, which inhibits the T-type calcium channel Cav3.2. This
calcium channel was highly expressed in human GBM specimens and enriched in GSCs.
Analyses of the The Cancer Genome Atlas and REMBRANDT databases confirmed
upregulation of Cav3.2 in a subset of tumors and showed that overexpression
associated with worse prognosis. Mibefradil treatment or RNAi-mediated
attenuation of Cav3.2 was sufficient to inhibit the growth, survival, and
stemness of GSCs and also sensitized them to temozolomide chemotherapy. Proteomic
and transcriptomic analyses revealed that Cav3.2 inhibition altered cancer
signaling pathways and gene transcription. Cav3.2 inhibition suppressed GSC
growth in part by inhibiting prosurvival AKT/mTOR pathways and stimulating
proapoptotic survivin and BAX pathways. Furthermore, Cav3.2 inhibition decreased
expression of oncogenes (PDGFA, PDGFB, and TGFB1) and increased expression of
tumor suppressor genes (TNFRSF14 and HSD17B14). Oral administration of mibefradil
inhibited growth of GSC-derived GBM murine xenografts, prolonged host survival,
and sensitized tumors to temozolomide treatment. Our results offer a
comprehensive characterization of Cav3.2 in GBM tumors and GSCs and provide a
preclinical proof of concept for repurposing mibefradil as a mechanism-based
treatment strategy for GBM. Cancer Res; 77(13); 3479-90. (c)2017 AACR.
PMID- 28512248
TI - Androgen Receptor Supports an Anchorage-Independent, Cancer Stem Cell-like
Population in Triple-Negative Breast Cancer.
AB - Preclinical and early clinical trials indicate that up to 50% of triple-negative
breast cancers (TNBC) express androgen receptor (AR) and are potentially
responsive to antiandrogens. However, the function of AR in TNBC and the
mechanisms by which AR-targeted therapy reduces tumor burden are largely unknown.
We hypothesized that AR maintains a cancer stem cell (CSC)-like tumor-initiating
population and serves as an antiapoptotic factor, facilitating anchorage
independence and metastasis. AR levels increased in TNBC cells grown in forced
suspension culture compared with those in attached conditions, and cells that
expressed AR resisted detachment-induced apoptosis. Culturing TNBC cells in
suspension increased the CSC-like population, an effect reversed by AR
inhibition. Pretreatment with enzalutamide (Enza) decreased the tumor-initiating
capacity of TNBC cells and reduced tumor volume and viability when administered
simultaneously or subsequent to the chemotherapeutic paclitaxel; simultaneous
treatment more effectively suppressed tumor recurrence. Overall, our findings
suggest that AR-targeted therapies may enhance the efficacy of chemotherapy even
in TNBCs with low AR expression by targeting a CSC-like cell population with
anchorage independence and invasive potential. Cancer Res; 77(13); 3455-66.
(c)2017 AACR.
PMID- 28512251
TI - Inhibition of the Cell Death Pathway in Nonalcoholic Steatohepatitis (NASH)
Related Hepatocarcinogenesis Is Associated with Histone H4 lysine 16
Deacetylation.
AB - Hepatocellular carcinoma (HCC) is one of the most aggressive human cancers, and
its incidence is steadily increasing worldwide. Recent epidemiologic findings
have suggested that the increased incidence of HCC is associated with obesity,
type II diabetes mellitus, and nonalcoholic steatohepatitis (NASH); however, the
mechanisms and the molecular pathogenesis of NASH-related HCC are not fully
understood. To elucidate the underlying mechanisms of the development of NASH
related HCC, we investigated the hepatic transcriptomic and histone modification
profiles in Stelic Animal Model mice, the first animal model of NASH-related HCC
to resemble the disease pathogenesis in humans. The results demonstrate that the
development of NASH-related HCC is characterized by progressive transcriptomic
alterations, global loss of histone H4 lysine 20 trimethylation (H4K20me3), and
global and gene-specific deacetylation of histone H4 lysine 16 (H4K16). Pathway
analysis of the entire set of differentially expressed genes indicated that the
inhibition of cell death pathway was the most prominent alteration, and this was
facilitated by persistent gene-specific histone H4K16 deacetylation.
Mechanistically, deacetylation of histone H4K16 was associated with
downregulation of lysine acetyltransferase KAT8, which was driven by
overexpression of its inhibitor nuclear protein 1 (Nupr1). The results of this
study identified a reduction of global and gene-specific histone H4K16
acetylation as a key pathophysiologic mechanism contributing to the development
of NASH-derived HCC and emphasized the importance of epigenetic alterations as
diagnostic and therapeutic targets for HCC.Implications: Histone H4K16
deacetylation induces silencing of genes related to the cell death that occurred
during the development of NASH-related HCC. Mol Cancer Res; 15(9); 1163-72.
(c)2017 AACR.
PMID- 28512249
TI - p62/SQSTM1 Cooperates with Hyperactive mTORC1 to Regulate Glutathione Production,
Maintain Mitochondrial Integrity, and Promote Tumorigenesis.
AB - p62/sequestosome-1 (SQSTM1) is a multifunctional adaptor protein and autophagic
substrate that accumulates in cells with hyperactive mTORC1, such as kidney cells
with mutations in the tumor suppressor genes tuberous sclerosis complex (TSC)1 or
TSC2. Here we report that p62 is a critical mediator of TSC2-driven
tumorigenesis, as Tsc2+/- and Tsc2f/f Ksp-CreERT2+ mice crossed to p62-/- mice
were protected from renal tumor development. Metabolic profiling revealed that
depletion of p62 in Tsc2-null cells decreased intracellular glutamine, glutamate,
and glutathione (GSH). p62 positively regulated the glutamine transporter Slc1a5
and increased glutamine uptake in Tsc2-null cells. We also observed p62-dependent
changes in Gcl, Gsr, Nqo1, and Srxn1, which were decreased by p62 attenuation and
implicated in GSH production and utilization. p62 attenuation altered
mitochondrial morphology, reduced mitochondrial membrane polarization and maximal
respiration, and increased mitochondrial reactive oxygen species and mitophagy
marker PINK1. These mitochondrial phenotypes were rescued by addition of
exogenous GSH and overexpression of Sod2, which suppressed indices of
mitochondrial damage and promoted growth of Tsc2-null cells. Finally, p62
depletion sensitized Tsc2-null cells to both oxidative stress and direct
inhibition of GSH biosynthesis by buthionine sulfoximine. Our findings show how
p62 helps maintain intracellular pools of GSH needed to limit mitochondrial
dysfunction in tumor cells with elevated mTORC1, highlighting p62 and redox
homeostasis as nodal vulnerabilities for therapeutic targeting in these tumors.
Cancer Res; 77(12); 3255-67. (c)2017 AACR.
PMID- 28512252
TI - Epigenetic Regulation of ZBTB18 Promotes Glioblastoma Progression.
AB - Glioblastoma (GBM) comprises distinct subtypes characterized by their molecular
profile. Mesenchymal identity in GBM has been associated with a comparatively
unfavorable prognosis, primarily due to inherent resistance of these tumors to
current therapies. The identification of molecular determinants of mesenchymal
transformation could potentially allow for the discovery of new therapeutic
targets. Zinc Finger and BTB Domain Containing 18 (ZBTB18/ZNF238/RP58) is a zinc
finger transcriptional repressor with a crucial role in brain development and
neuronal differentiation. Here, ZBTB18 is primarily silenced in the mesenchymal
subtype of GBM through aberrant promoter methylation. Loss of ZBTB18 contributes
to the aggressive phenotype of glioblastoma through regulation of poor prognosis
associated signatures. Restitution of ZBTB18 expression reverses the phenotype
and impairs tumor-forming ability. These results indicate that ZBTB18 functions
as a tumor suppressor in GBM through the regulation of genes associated with
phenotypically aggressive properties.Implications: This study characterizes the
role of the putative tumor suppressor ZBTB18 and its regulation by promoter
hypermethylation, which appears to be a common mechanism to silence ZBTB18 in the
mesenchymal subtype of GBM and provides a new mechanistic opportunity to
specifically target this tumor subclass. Mol Cancer Res; 15(8); 998-1011. (c)2017
AACR.
PMID- 28512250
TI - Introduction to the human gut microbiota.
AB - The human gastrointestinal (GI) tract harbours a complex and dynamic population
of microorganisms, the gut microbiota, which exert a marked influence on the host
during homeostasis and disease. Multiple factors contribute to the establishment
of the human gut microbiota during infancy. Diet is considered as one of the main
drivers in shaping the gut microbiota across the life time. Intestinal bacteria
play a crucial role in maintaining immune and metabolic homeostasis and
protecting against pathogens. Altered gut bacterial composition (dysbiosis) has
been associated with the pathogenesis of many inflammatory diseases and
infections. The interpretation of these studies relies on a better understanding
of inter-individual variations, heterogeneity of bacterial communities along and
across the GI tract, functional redundancy and the need to distinguish cause from
effect in states of dysbiosis. This review summarises our current understanding
of the development and composition of the human GI microbiota, and its impact on
gut integrity and host health, underlying the need for mechanistic studies
focusing on host-microbe interactions.
PMID- 28512253
TI - Infiltrating Myeloid Cells Exert Protumorigenic Actions via Neutrophil Elastase.
AB - Tissue infiltration and elevated peripheral circulation of granulocytic myeloid
derived cells is associated with poor outcomes in prostate cancer and other
malignancies. Although myeloid-derived cells have the ability to suppress T-cell
function, little is known about the direct impact of these innate cells on
prostate tumor growth. Here, it is reported that granulocytic myeloid-derived
suppressor cells (MDSC) are the predominant tumor-infiltrating cells in prostate
cancer xenografts established in athymic nude mice. MDSCs significantly increased
in number in the peripheral circulation as a function of xenograft growth and
were successfully depleted in vivo by Gr-1 antibody treatment. Importantly, MDSC
depletion significantly decreased xenograft growth. We hypothesized that
granulocytic MDSCs might exert their protumorigenic actions in part through
neutrophil elastase (ELANE), a serine protease released upon granulocyte
activation. Indeed, it was determined that NE is expressed by infiltrating immune
cells and is enzymatically active in prostate cancer xenografts and in prostate
tumors of prostate-specific Pten-null mice. Importantly, treatment with
sivelestat, a small-molecule inhibitor specific for NE, significantly decreased
xenograft growth, recapitulating the phenotype of Gr-1 MDSC depletion.
Mechanistically, NE activated MAPK signaling and induced MAPK-dependent
transcription of the proliferative gene cFOS in prostate cancer cells.
Functionally, NE stimulated proliferation, migration, and invasion of prostate
cancer cells in vitro IHC on human prostate cancer clinical biopsies revealed
coexpression of NE and infiltrating CD33+ MDSCs.Implications: This report
suggests that MDSCs and NE are physiologically important mediators of prostate
cancer progression and may serve as potential biomarkers and therapeutic targets.
Mol Cancer Res; 15(9); 1138-52. (c)2017 AACR.
PMID- 28512255
TI - Immune consequences of penfluridol treatment associated with inhibition of
glioblastoma tumor growth.
AB - Glioblastoma is the most common and lethal brain tumor associated with only 12%
median survival rate of patients. Despite the development of advanced surgical,
radiation or use of combinations of anti-cancer drugs, treatment for glioblastoma
patients is still a challenge. The major contributing factor in glioblastoma
progression and resistive nature is its ability to evade the immune surveillance.
Hence, modulating the immune system in glioblastoma tumors could be an important
strategy for anticancer therapeutics. Penfluridol, an antipsychotic drug has been
shown to have anti-cancer properties in our recently published studies. The
present study evaluates the immune response of penfluridol in glioblastoma
tumors. Our results demonstrated that penfluridol treatment significantly
suppressed glioblastoma tumor growth. Our current results demonstrated about 72%
suppression of myeloid derived suppressor cells (MDSCs) with penfluridol
treatment in mouse bearing U87MG glioblastoma tumors. MDSCs are known to increase
regulatory T cells (Treg), which are immunosuppressive in nature and suppresses
M1 macrophages that are tumor suppressive in nature. Our results also showed
suppression of regulatory T cells as well as elevation of M1 macrophages with
penfluridol treatment by 58% and 57% respectively. Decrease in CCL4 as well as
IFNgamma with penfluridol treatment was also observed indicating decrease in
overall tumor inflammation. This is the first report demonstrating immune
modulations by penfluridol treatment associated with glioblastoma tumor growth
suppression prompting further investigation to establish penfluridol as a
treatment option for glioblastoma patients.
PMID- 28512254
TI - Catecholamines facilitate VEGF-dependent angiogenesis via beta2-adrenoceptor
induced Epac1 and PKA activation.
AB - Chronic stress has been associated with the progression of cancer and antagonists
for beta-adrenoceptors (betaAR) are regarded as therapeutic option. As they are
also used to treat hemangiomas as well as retinopathy of prematurity, a role of
endothelial beta2AR in angiogenesis can be envisioned. We therefore investigated
the role of beta2AR-induced cAMP formation by analyzing the role of the cAMP
effector molecules exchange factor directly activated by cAMP 1 (Epac1) and
protein kinase A (PKA) in endothelial cells (EC). Epac1-deficient mice showed a
reduced amount of pre-retinal neovascularizations in the model of oxygen-induced
retinopathy, which is predominantly driven by vascular endothelial growth factor
(VEGF). siRNA-mediated knockdown of Epac1 in human umbilical vein EC (HUVEC)
decreased angiogenic sprouting by lowering the expression of the endothelial VEGF
receptor-2 (VEGFR-2). Conversely, Epac1 activation by beta2AR stimulation or the
Epac-selective activator cAMP analog 8-p-CPT-2'-O-Me-cAMP (8-pCPT) increased
VEGFR-2 levels and VEGF-dependent sprouting. Similar to Epac1 knockdown,
depletion of the monomeric GTPase Rac1 decreased VEGFR-2 expression. As Epac1
stimulation induces Rac1 activation, Epac1 might regulate VEGFR-2 expression
through Rac1. In addition, we found that PKA was also involved in the regulation
of angiogenesis in EC since the adenylyl cyclase (AC) activator forskolin (Fsk),
but not 8-pCPT, increased sprouting in Epac1-depleted HUVEC and this increase was
sensitive to a selective synthetic peptide PKA inhibitor. In accordance, beta2AR-
and AC-activation, but not Epac1 stimulation increased VEGF secretion in
HUVEC.Our data indicate that high levels of catecholamines, which occur during
chronic stress, prime the endothelium for angiogenesis through a beta2AR-mediated
increase in endothelial VEGFR-2 expression and VEGF secretion.
PMID- 28512264
TI - Gallic acid inhibits the release of ADAMTS4 in nucleus pulposus cells by
inhibiting p65 phosphorylation and acetylation of the NF-kappaB signaling
pathway.
AB - This study investigated the inhibitory effect of gallic acid (GA) on the release
of A Disintegrin and Metalloproteinase with Thrombospondin motifs 4 (ADAMTS4)
through the regulation of the NF-kappaB signaling pathway, which is closely
related to the matrix metalloproteinases in nucleus pulposus cells. Different
concentrations of GA were added to TNF-alpha-induced human nucleus pulposus cells
(hNPCs) and intervertebral disc degeneration rat model. ADAMTS-4 expression
increased both in the TNF-alpha-induced nucleus pulposus cells and intervertebral
disc degeneration rat model. By contrast, the release of ADAMTS-4 was reduced,
and the TNF-alpha-induced apoptosis of nucleus pulposus cells was significantly
inhibited after addition of GA at different concentrations. Further study found
that the levels of phosphorylated p65 (p-p65) was increased and the classical NF
kappaB signal pathway was activated after the nucleus pulposus cells were
stimulated by TNF-alpha. Meanwhile, GA suppressed the p65 phosphorylation and
inceased p65 deacetylation levels. As a consequence, GA can decrease the
expression of ADAMTS-4 in nucleus pulposus cells by regulating the
phosphorylation and acetylation of p65 in NF-kappaB signaling pathways.
PMID- 28512265
TI - Chaetocin enhances dendritic cell function via the induction of heat shock
protein and cancer testis antigens in myeloma cells.
AB - Dendritic cells (DC)-based vaccines are considered useful in cancer immuno
therapy, and the interactions of DC and dying tumor cells are important and
promising for cancer immunotherapy. We investigated whether chaetocin could be
used to induce death of myeloma cells, for loading onto DCs can affect DCs
function. In this study, we show that the dying myeloma cells treated with
chaetocin resulted in the induction of heat shock protein (HSP) 90, which was
inhibited by antioxidant N-acetyl cysteine, and showed an increase in the
expression of MAGE-A3 and MAGE-C1/CT7. DCs loaded with chaetocin-treated dying
myeloma cells produced low levels of IL-10 and enhanced the cross presentation of
DCs. Additionally, these DCs most potently inhibited regulatory T cells, induced
Th1 polarization and activated myeloma-specific cytotoxic T lymphocytes compared
with DCs loaded with UVB-irradiated dying myeloma cells. These results suggest
that the pretreatment of myeloma cells with chaetocin can enhance DC function
through the up-regulation of HSP90 and cancer testis antigens in dying myeloma
cells and can potently induce the Th1 polarization of DCs and myeloma-specific
cytotoxic T lymphocytes.
PMID- 28512268
TI - Advance directives: cancer patients' preferences and family-based decision
making.
AB - BACKGROUND: Advance directives are a sensitive issue among traditional Chinese
people, who usually refrain from mentioning this topic until it is imperative.
Medical decisions for cancer patients are made by their families, and these
decisions might violate patients' personal will. OBJECTIVES: This study aimed to
examine the acceptance of advance directives among Chinese cancer patients and
their families and patient participation in this procedure and, finally, to
analyze the moral risk involved. RESULTS: While 246 patients and their family
members refused official discussion of an advance directive, the remaining 166
patients and their families accepted the concept of an advance directive and
signed a document agreeing to give up invasive treatment when the anti-cancer
treatment was terminated. Of these, only 24 patients participated in the decision
making. For 101 patients, anti-cancer therapy was ended prematurely with as many
as 37 patients not told about their potential loss of health interests. MATERIALS
AND METHODS: Participants were 412 adult cancer patients from 9 leading hospitals
across China. An advance directive was introduced to the main decision makers for
each patient; if they wished to sign it, the advance directive would be
systematically discussed. A questionnaire was given to the oncologists in charge
of each patient to evaluate the interaction between families and patients,
patients' awareness of their disease, and participation in an advance directive.
CONCLUSIONS: Advance directives were not widely accepted among Chinese cancer
patients unless anti-cancer therapy was terminated. Most cancer patients were
excluded from the discussion of an advance directive.
PMID- 28512266
TI - Activating MAPK1 (ERK2) mutation in an aggressive case of disseminated juvenile
xanthogranuloma.
AB - Juvenile xanthogranuloma (JXG) is a rare histiocytic disorder that is usually
benign and self-limiting. We present a case of atypical, aggressive JXG harboring
a novel mitogen-activated protein kinase (MAPK) pathway mutation in the MAPK1
gene, which encodes mitogen-activated protein kinase 1 or extracellular signal
regulated 2 (ERK2). Our analysis revealed that the mutation results in
constitutive ERK activation that is resistant to BRAF or MEK inhibitors but
susceptible to an ERK inhibitor. These data highlight the importance of
identifying specific MAPK pathway alterations as part of the diagnostic workup
for patients with histiocytic disorders rather than initiating empiric treatment
with MEK inhibitors.
PMID- 28512270
TI - Abscopal Effect: Propitious or Pernicious?
AB - Recent advances in the field of radiation biology have increased our knowledge of
cellular responses to radiation and microenvironmental disseminations through
radiation at molecular level.
PMID- 28512269
TI - Oscillating expression of interleukin-16 in multiple myeloma is associated with
proliferation, clonogenic growth, and PI3K/NFKB/MAPK activation.
AB - Multiple myeloma (MM) is an incurable hematologic malignancy emerging from a
plasma cell clone located in the bone marrow and is characterized by a high rate
of fatal relapses after initially effective treatment. We have previously
identified Interleukin-16 (IL-16) as an important factor promoting the
proliferation of MM cells. We demonstrate here an upregulated, periodic
expression, and secretion of IL-16 by MM cells leading to high extracellular IL
16 levels. The level of IL-16 released from a given MM cell line correlated with
its proliferative activity. Establishing an inducible knockdown system and
performing gene expression arrays we observed an association between IL-16
expression and activation of PI3, NFkappaB and MAP kinase pathways and,
specifically, genes involved in tumor cell proliferation. Functional assays
showed that IL-16 knockdown reduced the proliferative activity with a significant
delay in cell cycle progression to G2 phase of conventional MM cells and
completely suppressed the growth of clonogenic MM cells, which are suspected to
be responsible for the high relapse rates in MM. Overall, our results demonstrate
that tumor-regenerating MM cells may be particularly susceptible to IL-16
neutralization, suggesting an important role of anti-IL-16 therapies in the
treatment of MM, particularly in combination with existing strategies targeting
the bulk of myeloma cells.
PMID- 28512271
TI - Staining Beverages and Cigarette Smoke on Composite Resin and Human Tooth
Fluorescence by Direct Spectrometry.
AB - INTRODUCTION: This study evaluated the fluorescence intensity (FI) of different
brands of composite resins (CRs) and compare those values with the FI of human
tooth, under the action of cigarette smoke (CI), coffee (CA), and soft drink
(CO), measured by direct spectrometry. MATERIALS AND METHODS: A total of 30
specimens of each brand (Filtek Z350, Esthet-X, Amelogen, Durafill) were made.
Others 30 tooth specimens (3 mm/diameter) were obtained from human molars using a
trephine bur. The specimens were randomly divided into three groups (n = 10),
according to substances: CI, CA, CO. The FI was directly measured using an optic
fiber associated with a spectrometer and was measured at baseline and after
staining. Data were submitted to Kruskal-Wallis, Dunnett, and Dunn tests.
RESULTS: Staining influenced FI mean values among CRs and between those with
human tooth. Z showed the closest FI mean values of tooth after staining.
CONCLUSION: Staining beverages and cigarette smoke negatively influenced on FI of
CR and human tooth. CLINICAL SIGNIFICANCE: The study shows darkening treatments
influenced on the fluorescent property of the dental tissues and restorative
materials according to the direct spectrometry analysis.
PMID- 28512272
TI - Apical Periodontitis and Endodontic Treatment in Patients with Type II Diabetes
Mellitus: Comparative Cross-sectional Survey.
AB - AIMS: The aims of this study were to investigate the prevalence of apical
periodontitis (AP) in diabetes mellitus (DM) patients compared with nondiabetic
patients and to examine the effect of glycemic control on the prevalence of AP.
MATERIALS AND METHODS: Radiographs of a group of DM patients were compared with
those of a matched nondiabetic group to identify AP. The diabetic group was
subdivided according to the level of glycemic control into two subgroups: A well
controlled DM and a poorly controlled DM. The periapical index score was used to
assess the periapical status. All groups were compared in regard to the presence
of AP lesions, the number of end-odontically treated teeth (ET), and the
percentage of failure of endodontically treated teeth (AP/ET ratio). Statistical
Package for the Social Sciences (SPSS version 20.0, Chicago, Illinois, USA) was
used for all the analyses; p <= 0.05 was considered as statistically significant.
RESULTS: The prevalence of AP was higher in diabetic group than in the
nondiabetic group (13.5 vs 11.9% respectively). Diabetic group had more teeth
with endodontic treatment ET compared with nondiabetic group (4.18 vs 1.82%
respectively); this difference was statistically significant (p = 0.001) along
with higher AP/ET ratio (27.7 vs 19.3 respectively). The poorly controlled DM
group had a higher prevalence of AP lesions compared with the well-controlled DM
group (18.29 vs 9.21 respectively). This difference was statistically significant
(p = 0.001); they also had a higher percentage of ET (5.55 vs 3.13% respectively)
and AP/ ET ratio (32.0 vs 21.8% respectively). CONCLUSION: This survey
demonstrates a higher prevalence of AP in DM patients compared with nondiabetic
group, with an increased prevalence of persistent chronic AP. Compared with a
well-controlled diabetic group, a poor glycemic control may be associated with a
higher prevalence of AP and increased rate of endodontic failures. CLINICAL
SIGNIFICANCE: Counseling diabetic patients, particularly those with poor glycemic
control, about the risk of failure of endodontic treatment can be part of
planning management, which could include refereeing diabetic patients who need
endodontic treatment for consultant care.
PMID- 28512273
TI - Comparison of Complications in Removable Mandibular Acrylic Splint and Cantilever
Herbst for Management of Class II Malocclusion: A Retrospective Study.
AB - INTRODUCTION: Numerous appliances are present for the management of class II
malocclusion. We have conducted a study to compare the clinical complications
during treatment with either a removable mandibular acrylic splint (RMS) or with
a cantilever Herbst (HC) appliance for the management of class II malocclusion.
MATERIALS AND METHODS: This study consisted of records of 114 patients (61 males,
53 females), who were divided into two groups. Group I received RMS and group II
received HC for the treatment of class II, Division 1 malocclusion. They were
further subdivided according to the telescopic system used [Dentaurum type I or
propulsor mandibular abzil (PMA)] and fixation mode (splint with crowns or
GripTite bands). Patients' clinical records were assessed to identify clinical
complications. RESULTS: The results of the study showed that the incidence of
complications during treatment in both groups was statistically nonsignificant.
The complications with either crown or band were also statistically
nonsignificant. The Dentaurum group showed more susceptibility to complications
than the PMA group. CONCLUSION: The PMA telescopic system is more efficient as
compared with Dentaurum. Complication resulting from Herbst appliance is
independent type of appliance used and mode of fixation. CLINICAL SIGNIFICANCE:
Herbst appliance is the treatment of choice for class II malocclusion.
PMID- 28512274
TI - Glucose Transporter 1 Expression in Odontogenic Keratocyst, Dentigerous Cyst, and
Ameloblastoma: An Immunohistochemical Study.
AB - INTRODUCTION: An array of odontogenic lesions manifest in the maxillofacial
region with variable presentations. The biological behavior of lesions, such as
odontogenic keratocyst (OKC), dentigerous cyst (DC), and ameloblastoma (AM)
always invite debate. Glucose transporter 1 (GLUT-1) is proven to be an indicator
of metabolic behavior of several benign and malignant neoplasms. AIM: The purpose
of this study was to evaluate the expression of GLUT-1 in OKC, DC, and AM to
understand their metabolic behavior. MATERIALS AND METHODS: Immunohistochemical
expression of GLUT-1 was evaluated in each of the 15 cases of OKC, DC, and AM.
The number of labeled cells, staining intensity, and membrane or cytoplasmic
expressions were the parameters assessed and analyzed using chi-square test.
RESULTS: All cases showed positive GLUT-1 expression: 86.6% OKC showed more than
50% labeled cells followed by DC (40%) and AM (26.5%); 53.3% OKC showed strong
intensity in comparison to AM, which showed weak intensity in 53.3% cases; 86.6%
of OKCs showed both membrane and cytoplasmic expression followed by DC (40%) and
AM (26.6%), whereas 73.3% of AM showed only membrane expression followed by DC
(60%) and OKC (13.3%). CONCLUSION: Odontogenic keratocyst was found out to be
more metabolically active followed by DC and AM.
PMID- 28512275
TI - Knowledge, Attitude, and Practice of Pregnant Women regarding Oral Health Status
and Treatment Needs following Oral Health Education in Pune District of
Maharashtra: A Longitudinal Hospital-based Study.
AB - INTRODUCTION: Pregnancy is a natural process that may create some changes in
different parts of the body including the oral cavity. These changes will lead to
oral diseases if enough and timely care of oral cavity is not taken. Women may
experience increased gingivitis or pregnancy gingivitis beginning in the second
or third month of pregnancy that increases in severity throughout the duration of
pregnancy. To motivate the patient toward oral health and implement the needed
prophylactic measures, a longitudinal study was planned to observe the effect of
oral health education during pregnancy on knowledge, attitude, practice, oral
health status, and treatment needs (TNs) of pregnant women belonging to different
socioeconomic groups. MATERIALS AND METHODS: A longitudinal study was conducted
among 112 pregnant women belonging to different socioeconomic groups to assess
the effect of oral health education on knowledge, attitude, practice, oral health
status, and TNs. The demographic details, knowledge, attitude, and practice of
pregnant women, and oral health status were collected through a predesigned
questionnaire by a principal investigator through an interview. Oral health
examination was carried out to assess oral health status using revised World
Health Organization Proforma 1997, and oral health education was given through
PowerPoint presentation to the participants in local language, i.e., Marathi,
after collecting the baseline data. Reinforcement of oral health education and
blanket referral was done at 14th week, and follow-up data were collected at 28th
week of gestation. The demographic details, such as age, sex, education,
occupation, income, and the questions based on knowledge, attitude, and practice
among participants were analyzed using number, percentage, and mean. RESULTS: At
baseline, knowledge was limited, attitude was positive, while the practice was
poor regarding oral health care during pregnancy in pregnant women belonging to
different socioeconomic groups. After oral health education and blanket referral,
at 28th week of gestation, knowledge regarding oral health care improved
drastically, attitude toward oral health became more positive, whereas practice
did not change much among all the pregnant women belonging to different
socioeconomic groups, probably indicating sociocultural influences. CONCLUSION:
Intensive oral health education during pregnancy leads to drastic improvement in
knowledge and attitude. Practice, gingival health, and the number of filled teeth
also improved to some extent. CLINICAL SIGNIFICANCE: Regular oral health
education programs should be conducted at community level among pregnant woman to
reduce the burden of oral diseases.
PMID- 28512276
TI - Osteoporosis Knowledge and Related Health Behavior among Women in Jazan Region,
Kingdom of Saudi Arabia.
AB - INTRODUCTION: Osteoporosis is a systemic bone disease that can be prevented to
some extent by awareness of its risk factors and related health behavior. The aim
of this study was to collect information about knowledge and awareness of
osteoporosis among women living in Jazan and to describe the type of food habits,
sociodemographic characteristics, and other osteoporosis-related health behavior.
MATERIALS AND METHODS: Self-administered questionnaires were used for data
collection. The total participants were 546 women: 88 (16.1%) were health
professionals and 458 (83.9%) non health professionals in the age range <=20 to
50 years. Data collection was facilitated by a trained intern female doctor of
dentistry whose task was to administer the distribution and collection of the
questionnaires. RESULTS: In total, 61.9% of health professionals and 54.3% of
nonhealth professionals scored highly on knowledge of osteoporosis. The
respondents of osteoporosis preventive food items were also highly knowledgeable
with 50.6 and 52.6% of health and nonhealth professionals respectively. About
48.1% of health professional and 44.2% of nonhealth professional scored low on
knowledge of osteoporosis behavior and attitude, vitamin supplements, and
sunlight exposure. The age effect on osteoporosis knowledge was 33.8% in young
age group and 30.7% in old age group. CONCLUSION: Our study shows that Jazan
women were highly knowledgeable and aware about osteoporosis and its related
health behavior and that health professionals and nonhealth professionals were
equally aware about osteoporosis-related health matters. CLINICAL SIGNIFICANCE:
Awareness and preventive behavior of osteoporosis can prevent or slow the
development of the disease.
PMID- 28512277
TI - Accuracy of Working Length Determination using NovApex and Root-ZX Apex Locators:
An in vitro Study.
AB - INTRODUCTION: This ex vivo study evaluated the accuracy of the Root-ZX electronic
apex locator (EAL) (J. Morita, Tokyo, Japan) and the NovApex (Forum Technologies,
Rishon Lezion, Israel) in determining the working length (WL) during endodontic
treatment. MATERIALS AND METHODS: Forty extracted single-rooted human teeth were
selected for this study. The actual WL was measured with visual technique by a
size #15 k-file under magnification. Then, the canal lengths were measured
electronically with both Root-ZX and NovApex apex locators within +/-0.5 and +/-1
mm. Mean percentage of data was analyzed between groups using paired t-test, with
a statistically significant level of p < 0.05. RESULTS: The accuracy of NovApex
apex locator was 85% within +/-0.5 mm and 92.5% within +/-1 mm. The accuracy of
Root-ZX apex locator was 70% within +/-0.5 mm and 97.5% within +/-1 mm. There was
no significant difference between the accuracy of the two EALs. CONCLUSION: Both
the NovApex and Root-ZX EALs are useful for measuring the WL with high accuracy.
CLINICAL SIGNIFICANCE: Given the importance of accurate WL determination in the
success of endodontic treatments, the accuracy of different apex locators should
be evaluated.
PMID- 28512278
TI - Use of Collagen Matrix for Augmentation of the Peri-implant Soft Tissue at the
Time of Immediate Implant Placement.
AB - AIM: The aim of this study was to determine the treatment outcome of the use of a
porcine monolayer collagen matrix (mCM) to augment peri-implant soft tissue in
conjunction with immediate implant placement as an alternative to patient's own
connective tissue. MATERIALS AND METHODS: A total of 27 implants were placed
immediately in 27 patients (14 males and 13 females, with a mean age of 52.2
years) with simultaneous augmentation of the soft tissue by the use of a mCM. The
patients were randomly divided into two groups: Group I: An envelope flap was
created and mCM was left coronally uncovered, and group II: A coronally
repositioned flap was created and the mCM was covered by the mucosa. Soft-tissue
thickness (STTh) was measured at the time of surgery (T0) and 6 months
postoperatively (T1) using a customized stent. Cone beam computed tomographies
(CBCTs) were taken from 12 representative cases at T1. A stringent plaque control
regimen was enforced in all the patients during the 6-month observation period.
RESULTS: Mean STTh change was similar in both groups (0.7 +/- 0.2 and 0.7 +/- 0.1
mm in groups I and II respectively). The comparison of STTh between T0 and T1
showed a statistically significant increase of soft tissue in both groups I and
II as well as in the total examined population (p < 0.001). The STTh change as
well as matrix thickness loss were comparable in both groups (p > 0.05). The
evaluation of the CBCTs did not show any signs of resorption of the buccal bone
plate. CONCLUSION: Within the limitations of this study, it could be concluded
that the collagen matrix used in conjunction with immediate implant placement
leads to an increased thickness of peri-implant soft tissue independent of the
flap creation technique and could be an alternative to connective tissue graft.
CLINICAL SIGNIFICANCE: The collagen matrix used seems to be a good alternative to
patient's own connective tissue and could be used for the soft tissue
augmentation around dental implants.
PMID- 28512279
TI - Antimicrobial Potential of Plant Extracts and Chemical Fractions of Sideroxylon
obtusifolium (Roem. & Schult.) T.D. Penn on Oral Microorganisms.
AB - AIM: The aim of this study is to evaluate the in vitro antimicrobial activity of
plant extracts and chemical fractions of Sideroxylon obtusifolium T.D. Penn on
Streptococcus mutans, Streptococcus oralis, Streptococcus salivarius,
Streptococcus parasanguinis, and Candida albicans as well as to identify the
chemical classes found in the bioactive extracts possessing better activity.
MATERIALS AND METHODS: Freeze-dried hydroalcoholic extracts of the bark and
leaves (LC and LF respectively) and ethanol extracts of bark and leaves (EC and
EF respectively) of S. obtusifolium were assessed for antimicrobial potential by
determining the minimum inhibitory concentration (MIC), minimum bactericidal
concentration, and minimum fungicidal concentration (MFC). The tests were
performed by microdilu-tion method (in triplicate) in three independent
experiments. Phytochemical characterization was performed by quantification of
total polyphenols, total flavonoids, and condensed tannins. RESULTS: The EC
extract presented weak antimicrobial potential on the growth of S. mutans (MIC =
1000 MUg/mL); all extracts showed moderate inhibitory activity on the growth of
C. albicans (MIC = 500 MUg/mL). The dichloromethane and n-butanol fractions of LF
extracts showed moderate growth inhibitory activity (MIC = 250 MUg/mL) on C.
albicans and fungicide potential (MFC/MIC = 2). The phytochemical
characterization revealed a predominance of total polyphenols (EC = 29.23%; LC =
25.98%) and condensed tannins (LC = 38.84%; LF = 17.78%). CONCLUSION: The
dichloromethane and n-butanol fractions of S. obtusifolium LF extract showed
antifungal activity against C. albicans, with the potential for bioprospection of
phytocom-pounds for the treatment of periodontal fungal diseases caused by this
microorganism. The effect may be related to phyto-chemical compounds from the
polyphenol and condensed tannin classes. CLINICAL SIGNIFICANCE: Research for new
oral microbial disease treatment alternatives in bioactive compounds from
medicinal plants is of clinical relevance and scientific interest since many
therapeutic antifungal agents do not obtain the effectiveness expected due to
microbial resistance, or to adverse effects on human tissues.
PMID- 28512280
TI - Herpes Simplex 1 and Periopathogen Role in Peri-implantitis.
AB - INTRODUCTION: The objectives of this study were to compare the qualitative and
quantitative profiles of herpes simplex virus type I (HSV-1) in implant surfaces
between participants with peri-implantitis (PI) and Healthy peri-implant tissues
and to quantitatively assess the relation between HSV-1 and periopathogens inside
the microbiological profile associated with PI. MATERIALS AND METHODS: A total of
40 patients with PI and 40 with healthy peri-implant tissues (HI) were recruited.
Plaque samples from peri-implant sulcus and internal implant connections were
analyzed using quantitative real-time polymerase chain reaction to detect and
quantify HSV-1 and periodonto-pathogens. Frequencies of detection and levels of
microorganisms were compared between PI and HI; the frequencies and levels of
periodontopathogens were compared between HSV-1+ and HSV-1- PI to assess
qualitative relations between HSV-1 and bacteria. Correlation between HSV-1 and
periodontopatho-gens levels was assessed in PI and HI. RESULTS: A total of 77
dental implants affected by PI, and 113 HIs were included. The HSV-1 prevalence
was slightly higher in PI compared with controls (33.3 vs 23.8%; p > 0.05); HSV-1
was detected in external samples more frequently compared with internal samples.
The HSV-1-positive patients revealed higher median loads of Prevotella intermedia
(Pi) and Campylobacter rectus (Cr) compared with HSV-1-negative patients. In the
PI group, a significant positive correlation was evidenced between HSV-1 and
Tannerella forsythia, Parvimonas micra (Pm), Fusobacterium nucleatum, and Cr
levels, while in the HI, positive correlation between HSV-1 and Aggregatibacter
actinomycetemcomitans, Pi, and Pm was established. CONCLUSION: The HSV-1
prevalence cannot be used to identify PI. The HSV-1 was found in similar levels
of PI and HI patients after an average of 6 years of loaded implants. The HSV-1
prevalence cannot be used to identify implants with or without the presence of
PI. CLINICAL SIGNIFICANCE: Although HSV-1 is detected in PI site, HSV-1 may
represent an unspecific indicator for the host response to the bacterial
challenge observed in PI.
PMID- 28512281
TI - Intricate Assessment and Evaluation of Long-term Implant Success as affected by
Clinicomicrobial and Salivary Diagnostics in Type II Diabetic Patients: A
Longitudinal Study.
AB - INTRODUCTION: Replacement of missing teeth by dental implants is one of the most
common methods employed these days. Because of significant advancement in the
design of implants and modifications in the procedure of dental implant surgery,
the survival rate of the dental implants has reached up to approximately 95%.
Osseointegration is one of the important factors affecting the survival of dental
implants. Apart from these, the body's physiologic alterations can also
predispose the dental implants for failure. Diabetes is one such metabolic
disease characterized by abnormal or delayed wound healing. Hence, we assessed
the clinicomicrobial and salivary profile of diabetic patients undergoing
rehabilitation by dental implants. MATERIALS AND METHODS: This study included
diabetic patients who underwent dental implant surgeries for prosthetic
rehabilitation. Follow-up records of the patients' up to 1 year were maintained.
Various clinicoradiographic and periodontal parameters were measured at various
time intervals during follow-up time; 25 mL of salivary and blood sample was
taken from all the subjects and was sent to the laboratories for assessment of
various salivary biomarkers. All the results were analyzed by Statistical Package
for the Social Sciences software. RESULTS: The mean level of interleukin-p at
baseline time was found to be 2.38 and 2.21 in diabetic group and control group
respectively. While comparing the levels of osteoprotegerin in both study groups,
a significant correlation was obtained. In diabetic and control group, 62 and 61
years was the mean age of the patients respectively. No significant correlation
was obtained while comparing the microbial flora of diabetic and control group.
CONCLUSION: In both diabetic and nondiabetic patients, similar microbial,
salivary marker, and clinicoradiological patterns were seen. CLINICAL
SIGNIFICANCE: Diabetic patients who maintain their body's metabolic rate show
similar success rate of dental implants as seen in nondiabetic patients.
PMID- 28512282
TI - Orthopedic Effect of Chin Cup during Mixed Dentition Stage.
AB - INTRODUCTION: Chin cup (CC) therapy has been used as the traditional appliance
for treating class III malocclusion during mixed dentition period. The aim of
this study was to investigate the effect of CC on the improvement of skeletal and
dentoalveo-lar skeletal changes in class III patients during mixed dentition
stage. MATERIALS AND METHODS: A total of 30 patients (7-9 years old) with
skeletal class III malocclusion were selected based on clinical and cephalometric
examination. Out of 30 patients, 20 underwent CC therapy. All orthodontic records
and measurements were taken before and after treatment. Similar records were
collected from the control group. The lateral cephalometric films were traced
before and after treatment and analyzed. RESULTS: There was a significant
improvement in maxillary and the mandibular skeletal measurements after CC
therapy. Improvement of ANB angle and an increase in Wits appraisal have been
detected in the treated group according to intermaxillary skeletal variables.
CONCLUSION: The study concluded that the CC therapy is effective for correcting
skeletal class III malocclusion along with positive changes in the dentoskeletal
variables during the mixed dentition stage.
PMID- 28512283
TI - Unusual Root Canal Irrigation Solutions.
AB - Microorganisms and their by-products play a critical role in pulp and
periradicular pathosis. Therefore, one of the main purposes of root canal
treatment is disinfection of the entire system of the canal. This aim may be
obtained using mechanical preparation, chemical irrigation, and temporary
medication of the canal. For this purpose, various irrigation solutions have been
advocated. Common root canal irrigants, such as sodium hypochlorite,
chlorhexidine, and a mixture of tetracycline, acid, and detergent have been
extensively reviewed. The aim of this review was to address the less common newer
root canal irrigation solutions, such as citric acid, maleic acid,
electrochemically activated water, green tea, ozonated water, and SmearClear.
PMID- 28512284
TI - Improved Survival in Patients with Resected Pancreatic Carcinoma Using
Postoperative Intensity-Modulated Radiotherapy and Regional Intra-Arterial
Infusion Chemotherapy.
AB - BACKGROUND We assessed the role of adjuvant intensity-modulated radiotherapy
(IMRT) in combination with chemotherapy for pancreatic carcinomas after curative
resection and identified prognostic factors related to pancreatic carcinoma after
multidisciplinary treatment strategies. MATERIAL AND METHODS Pancreatic carcinoma
patients (n=61) who received adjuvant radiotherapy after resection (median dose,
50.4 Gy) between 2010 and 2016 were retrospectively identified. Sixty patients
received chemotherapy, including concurrent chemoradiotherapy (CCRT), systemic
chemotherapy, and regional intra-arterial infusion chemotherapy (RIAC). The
Kaplan-Meier method was used to measure the 3-year overall survival (OS) and
disease-free survival (DFS) rates. Log-rank univariate analysis and multivariate
Cox regression model analysis were used to identify prognostic factors. RESULTS
Median follow-up time was 25.5 (range, 4.9-59.7) months. The 3-year OS and DFS
rates were 31.0% and 16.1%, respectively. The median OS and DFS were 27.4 and
16.7 months, respectively. Multivariate analysis indicated that independent
favorable predictors for OS were CCRT (p=0.039) and postoperative RIAC (p=0.044).
Moreover, postoperative RIAC (p=0.027), and pre-radiotherapy CA19-9 <=37 U/mL
(p=0.0080) were independent favorable predictors for DFS. The combination of
radiotherapy and chemotherapy was tolerated well by the patients, and no
treatment-related death occurred. CONCLUSIONS Combined IMRT and adjuvant
chemotherapy appeared safe and effective for pancreatic carcinoma. CCRT was
associated with improved survival with acceptable toxicity. We propose that
radiotherapy could be a part of postoperative treatment, but it should be
administered concurrently with chemotherapy. Adding RIAC was associated with
improved OS and DFS and it could be integrated into the postoperative treatment
regimen.
PMID- 28512285
TI - Coronary Aneurysm Formation After Bioresorbable Vascular Scaffold Implantation
Resulting in Acute Myocardial Infarction.
AB - BACKGROUND Development of a true coronary aneurysm after percutaneous coronary
intervention is a rare event, and a coronary aneurysm resulting in acute
myocardial infarction is even rarer. Coronary aneurysm formation after
bioresorbable vascular scaffold (BVS) implantation, eventually leading to
thrombosis, embolization, and myocardial infarction, has never been reported
before in the literature. CASE REPORT A 62-year-old man received an elective BVS
for a proximal left anterior descending lesion. Two months later, he suffered
from a non-ST-segment myocardial infarction. Coronary angiography showed a non
significant distal stent edge restenosis over the left anterior descending artery
and a small aneurysm after the first diagonal branch. A XIENCE Xpedition stent
was used to cover both lesions and final angiography showed shrinkage of the
aneurysm and resolution of the restenosis. CONCLUSIONS Since a consensus or an
established treatment guideline for treating coronary aneurysms is currently
lacking, each case should be treated with caution and should be guided by the
accompanying circumstances presented during the procedure. Although size,
rapidity of growth, and the presence of high-risk features are the main
determinants of whether to treat the lesion, the inherent risk of restenosis or
reocclusion after use of drug-eluting stents and the coronary intervention
procedure itself should also be taken into consideration. However, one must not
take lightly a small coronary aneurysm when discovered, as the abnormal fluid
dynamics inside may result in thrombus formation and embolization. The
fundamental technical aspects of stent deployment, such as avoiding
overstretching during lesion preparation, use of balloons shorter than the
implanted device, and normal-to-normal or healthy "landing zone" of the device,
should be followed.
PMID- 28512286
TI - Multifaceted catalytic hydrogenation of amides via diverse activation of a
sterically confined bipyridine-ruthenium framework.
AB - Amides are ubiquitous and abundant in nature and our society, but are very stable
and reluctant to salt-free, catalytic chemical transformations. Through the
activation of a "sterically confined bipyridine-ruthenium (Ru) framework
(molecularly well-designed site to confine adsorbed H2 in)" of a precatalyst,
catalytic hydrogenation of formamides through polyamide is achieved under a wide
range of reaction conditions. Both C=O bond and C-N bond cleavage of a lactam
became also possible using a single precatalyst. That is, catalyst diversity is
induced by activation and stepwise multiple hydrogenation of a single precatalyst
when the conditions are varied. The versatile catalysts have different structures
and different resting states for multifaceted amide hydrogenation, but the common
structure produced upon reaction with H2, which catalyzes hydrogenation, seems to
be "H-Ru-N-H."
PMID- 28512287
TI - Levels of Faecal Calprotectin and Magnetic Resonance Enterocolonography Correlate
with Severity of Small Bowel Crohn's Disease: A Retrospective Cohort Study.
AB - Few studies have evaluated the usefulness of fecal calprotectin (FC) or magnetic
resonance enterography (MRE) in diagnosing active Crohn's disease (CD) of the
small bowel. In the study, we investigated the reliability of FC and MRE in
assessing the activity of ileal CD and further explored the relationship between
levels of FC and MRE scores. A total of 221 patients were diagnosed with ileal or
ileo-colitis CD in our department between July 2012 and October 2016. The global
magnetic resonance index of activity (MaRIA) correlated with the simple
endoscopic score for CD (SES-CD) (r = 0.527, P = 0.005). When analysed segment-by
segment, a significant correlation was still observed (r = 0.590, P < 0.001). The
SES-CD correlated closest with FC (r = 0.503), followed by CRP (r = 0.461), ESR
(0.377) and the CDAI (r = 0.320). In receiver operating characteristic (ROC)
analyses, the FC cut-off value of mucosal healing was 213.1 MUg/g, with 76.1%
sensitivity and 66.7% specificity. As for MaRIA, a cut-off value of 6.8 for each
segment provided a sensitivity of 100% and a specificity of 79.2%. No agreement
between MaRIA and FC levels was found. In conclusion, a combination of FC levels
and MaRIA could be effective in monitoring mucosal activity in patients with
small bowel CD.
PMID- 28512289
TI - A genetic screen in combination with biochemical analysis in Saccharomyces
cerevisiae indicates that phenazine-1-carboxylic acid is harmful to vesicular
trafficking and autophagy.
AB - The environmentally friendly antibiotic phenazine-1-carboxylic acid (PCA)
protects plants, mammals and humans effectively against various fungal pathogens.
However, the mechanism by which PCA inhibits or kills fungal pathogens is not
fully understood. We analyzed the effects of PCA on the growth of two fungal
model organisms, Saccharomyces cerevisiae and Candida albicans, and found that
PCA inhibited yeast growth in a dose-dependent manner which was inversely
dependent on pH. In contrast, the commonly used antibiotic hygromycin B acted in
a dose-dependent manner as pH increased. We then screened a yeast mutant library
to identify genes whose mutation or deletion conferred resistance or sensitivity
to PCA. We isolated 193 PCA-resistant or PCA-sensitive mutants in clusters,
including vesicle-trafficking- and autophagy-defective mutants. Further analysis
showed that unlike hygromycin B, PCA significantly altered intracellular
vesicular trafficking under growth conditions and blocked autophagy under
starvation conditions. These results suggest that PCA inhibits or kills
pathogenic fungi in a complex way, in part by disrupting vesicular trafficking
and autophagy.
PMID- 28512288
TI - Lactic acid bacteria-specific induction of CD4+Foxp3+T cells ameliorates shrimp
tropomyosin-induced allergic response in mice via suppression of mTOR signaling.
AB - The beneficial effects of probiotics have been described in allergic
sensitization and diseases; however, many questions remain unanswered, such as
characteristics of the most effective strains in modulation of allergic responses
and how orally administered probiotics affect the systemic immune system. In the
present work, oral administration of five lactic acid bacteria strains showed
variable effects on protection against the allergic reaction in a mouse model of
food allergy to shrimp tropomyosin (ST). The most effective anti-allergic strain,
Bacillus coagulans 09.712 (Bc), greatly improved epithelial barrier function and
increased lymphocytes proliferation. Moreover, Bc suppresses ST sensitization by
altering Th1/Th2/Treg balance as a result of strong induction of CD4+Foxp3+Tregs
in combination with IL-10 producing. Bc-specific induction of CD4+Foxp3+ Tregs
also suppresses Th17 pro-inflammatory response in this mouse model. Finally, the
intake of Bc suppresses mTOR activation and thus the phosphorylation of
downstream factors. Inhibition of mTOR signaling by Bc further results in FOXP3
up-regulation and GATA-3 down-regulation, which, in turn, facilitate to control
Th2-predominant and Th17 pro-inflammatory responses caused by ST. Our work
provides further characterization of the anti-allergic effects of probiotic LAB
strains, and identifies new targets for preventive and curative treatment of food
allergies.
PMID- 28512290
TI - Evolution of Drug-resistant Acinetobacter baumannii After DCD Renal
Transplantation.
AB - Infection after renal transplantation remains a major cause of morbidity and
death, especially infection from the extensively drug-resistant bacteria, A.
baumannii. A total of fourteen A. baumannii isolates were isolated from the
donors' preserved fluid from DCD (donation after cardiac death) renal
transplantation and four isolates in the recipients' draining liquid at the
Kidney Disease Center, The First Affiliated Hospital, College of Medicine,
Zhejiang University, from March 2013 to November 2014. An outbreak of A.
baumannii emerging after DCD renal transplantation was tracked to understand the
transmission of the pathogen. PFGE displayed similar DNA patterns between
isolates from the same hospital. Antimicrobial susceptibility tests against
thirteen antimicrobial agents were determined using the K-B diffusion method and
eTest. Whole-genome sequencing was applied to investigate the genetic
relationship of the isolates. With the clinical data and research results, we
concluded that the A. baumannii isolates 3R1 and 3R2 was probably transmitted
from the donor who acquired the bacteria during his stay in the ICU, while
isolate 4R1 was transmitted from 3R1 and 3R2 via medical manipulation. This study
demonstrated the value of integration of clinical profiles with molecular methods
in outbreak investigation and their importance in controlling infection and
preventing serious complications after DCD transplantation.
PMID- 28512292
TI - Effects of treadmill running with different intensity on rat subchondral bone.
AB - Subchondral bone (SB) is recognized as a key factor in normal joint protection,
not only does it provide a shock absorbing and supportive function for the
cartilage, but it may also be important for cartilage metabolism. Mechanical
loading is considered to be a critical regulator of skeletal homeostasis,
including bone and cartilage. It is suggested that both cartilage and bone may
respond to mechanical loading in an intensity-dependent manner. In this report,
we have discovered that the subchondral plate became thicker with higher bone
mineral density (BMD) and lower porosity, while trabecular bone became more plate
like and denser with higher BMD in high-intensity running (HIR) group. Further,
HIR led to highly remodeled, less mineralized, and stiffer subchondral plate and
trabecular bone. On the contrary, low-intensity running and moderate-intensity
running failed to result in considerable changes in microstructure, composition
and hardness. Our findings suggested that running affects SB in an intensity
dependent manner. In addition, HIR may induce change in organization and
composition of SB, and consequently alter its mechanical properties. HIR-induced
"brittle and stiff" SB may adversely affect the overlying articular cartilage.
PMID- 28512291
TI - Characterization of Mechanically Matched Hydrogel Coatings to Improve the
Biocompatibility of Neural Implants.
AB - Glial scar is a significant barrier to neural implant function. Micromotion
between the implant and tissue is suspected to be a key driver of glial scar
formation around neural implants. This study explores the ability of soft
hydrogel coatings to modulate glial scar formation by reducing local strain. PEG
hydrogels with controllable thickness and elastic moduli were formed on the
surface of neural probes. These coatings significantly reduced the local strain
resulting from micromotion around the implants. Coated implants were found to
significantly reduce scarring in vivo, compared to hard implants of identical
diameter. Increasing implant diameter was found to significantly increase
scarring for glass implants, as well as increase local BBB permeability, increase
macrophage activation, and decrease the local neural density. These results
highlight the tradeoff in mechanical benefit with the size effects from
increasing the overall diameter following the addition of a hydrogel coating.
This study emphasizes the importance of both mechanical and geometric factors of
neural implants on chronic timescales.
PMID- 28512293
TI - Near Infrared Quantum Cutting Luminescence of Er3+/Tm3+ Ion Pairs in a Telluride
Glass.
AB - The multiphoton near-infrared, quantum cutting luminescence in Er3+/Tm3+ co-doped
telluride glass was studied. We found that the near-infrared 1800-nm luminescence
intensity of (A) Er3+(8%)Tm3+(0.5%):telluride glass was approximately 4.4 to 19.5
times larger than that of (B) Tm3+(0.5%):telluride glass, and approximately 5.0
times larger than that of (C) Er3+(0.5%):telluride glass. Additionally, the
infrared excitation spectra of the 1800 nm luminescence, as well as the visible
excitation spectra of the 522 nm and 652 nm luminescence, of (A)
Er3+(8%)Tm3+(0.5%):telluride glass are very similar to those of Er3+ ions in (C)
Er3+(0.5%):telluride glass, with respect to the shapes of their excitation
spectral waveforms and peak wavelengths. Moreover, we found that there is a
strong spectral overlap and energy transfer between the infrared luminescence of
Er3+ donor ions and the infrared absorption of Tm3+ acceptor ions. The efficiency
of this energy transfer {4I13/2(Er3+) -> 4I15/2(Er3+), 3H6(Tm3+) -> 3F4(Tm3+)}
between the Er3+ and Tm3+ ions is approximately 69.8%. Therefore, we can conclude
that the observed behaviour is an interesting multiphoton, near-infrared, quantum
cutting luminescence phenomenon that occurs in novel Er3+-Tm3+ ion pairs. These
findings are significant for the development of next-generation environmentally
friendly germanium solar cells, and near-to-mid infrared (1.8-2.0 MUm) lasers
pumped by GaN light emitting diodes.
PMID- 28512294
TI - The potential use of cuticular hydrocarbons and multivariate analysis to age
empty puparial cases of Calliphora vicina and Lucilia sericata.
AB - Cuticular hydrocarbons (CHC) have been successfully used in the field of forensic
entomology for identifying and ageing forensically important blowfly species,
primarily in the larval stages. However in older scenes where all other
entomological evidence is no longer present, Calliphoridae puparial cases can
often be all that remains and therefore being able to establish the age could
give an indication of the PMI. This paper examined the CHCs present in the lipid
wax layer of insects, to determine the age of the cases over a period of nine
months. The two forensically important species examined were Calliphora vicina
and Lucilia sericata. The hydrocarbons were chemically extracted and analysed
using Gas Chromatography - Mass Spectrometry. Statistical analysis was then
applied in the form of non-metric multidimensional scaling analysis (NMDS),
permutational multivariate analysis of variance (PERMANOVA) and random forest
models. This study was successful in determining age differences within the empty
cases, which to date, has not been establish by any other technique.
PMID- 28512296
TI - Entanglement monogamy in three qutrit systems.
AB - By introducing an arbitrary-dimensional multipartite entanglement measure, which
is defined in terms of the reduced density matrices corresponding to all possible
two partitions of the entire system, we prove that multipartite entanglement
cannot be freely shared among the parties in both n-qubit systems and three
qutrit systems. Furthermore, our result implies that the satisfaction of the
entanglement monogamy is related to the number of particles in the quantum
system. As an application of three-qutrit monogamy inequality, we give a
condition for the separability of a class of two-qutrit mixed states in a 3 ? 3
system.
PMID- 28512297
TI - Flexible Two-Photon Interference Fringes with Thermal Light.
AB - Flexible interference patterning is an important tool for adaptable measurement
precisions. We report on experimental results of controllable two-photon
interference fringes with thermal light in an incoherent rotational shearing
interferometer. The two incoherent beams in the interferometer are orthogonally
polarized, and their wavefront distributions differ only in an angle of rotation.
The spacings and directions of the two-photon interference fringes vary with the
rotation angle, as illustrated in three cases of two-photon correlation
measurements in experiment.
PMID- 28512298
TI - Genetic load makes cancer cells more sensitive to common drugs: evidence from
Cancer Cell Line Encyclopedia.
AB - Genetic alterations initiate tumors and enable the evolution of drug resistance.
The pro-cancer view of mutations is however incomplete, and several studies show
that mutational load can reduce tumor fitness. Given its negative effect, genetic
load should make tumors more sensitive to anticancer drugs. Here, we test this
hypothesis across all major types of cancer from the Cancer Cell Line
Encyclopedia, which provides genetic and expression data of 496 cell lines
together with their response to 24 common anticancer drugs. We found that the
efficacy of 9 out of 24 drugs showed significant association with genetic load in
a pan-cancer analysis. The associations for some tissue-drug combinations were
remarkably strong, with genetic load explaining up to 83% of the variance in the
drug response. Overall, the role of genetic load depended on both the drug and
the tissue type with 10 tissues being particularly vulnerable to genetic load. We
also identified changes in gene expression associated with increased genetic
load, which included cell-cycle checkpoints, DNA damage and apoptosis. Our
results show that genetic load is an important component of tumor fitness and can
predict drug sensitivity. Beyond being a biomarker, genetic load might be a new,
unexplored vulnerability of cancer.
PMID- 28512295
TI - cAMP-dependent cell differentiation triggered by activated CRHR1 in hippocampal
neuronal cells.
AB - Corticotropin-releasing hormone receptor 1 (CRHR1) activates the atypical soluble
adenylyl cyclase (sAC) in addition to transmembrane adenylyl cyclases (tmACs).
Both cAMP sources were shown to be required for the phosphorylation of ERK1/2
triggered by activated G protein coupled receptor (GPCR) CRHR1 in neuronal and
neuroendocrine contexts. Here, we show that activated CRHR1 promotes growth
arrest and neurite elongation in neuronal hippocampal cells (HT22-CRHR1 cells).
By characterising CRHR1 signalling mechanisms involved in the neuritogenic
effect, we demonstrate that neurite outgrowth in HT22-CRHR1 cells takes place by
a sAC-dependent, ERK1/2-independent signalling cascade. Both tmACs and sAC are
involved in corticotropin-releasing hormone (CRH)-mediated CREB phosphorylation
and c-fos induction, but only sAC-generated cAMP pools are critical for the
neuritogenic effect of CRH, further highlighting the engagement of two sources of
cAMP downstream of the activation of a GPCR, and reinforcing the notion that
restricted cAMP microdomains may regulate independent cellular processes.
PMID- 28512299
TI - Transgenic Bt rice lines producing Cry1Ac, Cry2Aa or Cry1Ca have no detrimental
effects on Brown Planthopper and Pond Wolf Spider.
AB - Transgenic rice expressing cry genes from the bacterium Bacillus thuringiensis
(Bt rice) is highly resistant to lepidopteran pests. The brown planthopper (BPH,
Nilaparvata lugens) is the main non-target sap-sucking insect pest of Bt
transgenic rice. The pond wolf spider (PWS, Pardosa pseudoannulata) is one of the
most dominant predators of BPH in rice fields. Consequently, the safety
evaluation of Bt rice on BPH and PWS should be conducted before
commercialization. In the current study, two experiments were performed to assess
the potential ecological effects of Bt rice on BPH and PWS: (1) a tritrophic
experiment to evaluate the transmission of Cry1Ac, Cry2Aa and Cry1Ca protein in
the food chain; and (2) binding assays of Cry1Ac, Cry2Aa and Cry1Ca to midgut
brush border membrane proteins from BPH and PWS. Trace amounts of the three Cry
proteins were detected in BPH feeding on Bt rice cultivars, but only Cry1Ac and
Cry2Aa proteins could be transferred to PWS through feeding on BPH. In vitro
binding of biotinylated Cry proteins and competition assays in midgut protein
vesicles showed weak binding, and ligand blot analysis confirmed the binding
specificity. Thus, we inferred that the tested Bt rice varieties have negligible
effects on BPH and PWS.
PMID- 28512300
TI - Overview of influenza vaccination policy in Beijing, China: Current status and
future prospects.
AB - Vaccination is the best available way to prevent influenza infections and related
complications. Little information is available on vaccination policy in the
world's most populous country, China. In China, influenza vaccine is not included
in the national immunization programme. Citizens seek the vaccine on their own.
Since 2007, Beijing, ahead of most cities in China, has offered free influenza
vaccine for seniors aged at least 60 years and for primary and middle school
students. There has been limited evaluation of the policy. We introduce and
evaluate the government-funded influenza immunization policy in Beijing.
Available data showed that the policy greatly increased the vaccine uptake rate
in the population qualifying for free vaccination. Evidence of impact in a single
influenza season on all high-risk populations was unclear. We suggest that
further evaluation over multiple influenza seasons and in each high-risk group
are required to inform future policy development in Beijing.
PMID- 28512301
TI - Maternal antioxidant provisioning mitigates pollutant-induced oxidative damage in
embryos of the temperate sea urchin Evechinus chloroticus.
AB - One mechanism of pollution resistance in marine populations is through
transgenerational plasticity, whereby offspring capacity to resist pollution
reflects parental exposure history. Our study aimed to establish correlations
between oxidative stress biomarkers and key reproductive fitness parameters in
the temperate sea urchin Evechinus chloroticus following exposure to dietary
polycyclic aromatic hydrocarbons (PAHs). PAH-exposed adults exhibited total gonad
tissue concentrations of PAHs in excess of 4 and 5 times baseline levels, for
females and males respectively. Antioxidant enzymes were upregulated and
oxidative lipid and protein damage to gonad tissues occurred. In addition, early
stage offspring reflected maternal antioxidant status, with progeny derived from
exposed females demonstrating significantly higher baselines than those derived
from control females. Maternal exposure history enhanced the capacity of embryos
to minimise oxidative damage to lipids and proteins following exposure to
additional PAHs, but provided less of an advantage in protection against
oxidative DNA damage. Abnormal embryonic development was largely independent of
oxidative damage, remaining high in all embryo populations regardless of parental
PAH-history. Overall, results document evidence for maternal transfer of
antioxidant potential in E. chloroticus, but imply that a short-term inherited
resilience against oxidative stress may not necessarily translate to a fitness or
survival gain.
PMID- 28512302
TI - Olfactory threshold and odor discrimination ability in children - evaluation of a
modified "Sniffin' Sticks" test.
AB - The clinical diagnostics of olfactory dysfunction in children turns out to be
challenging due to low attention span, insufficient linguistic development and
lack of odor experiences. Several smell tests have been developed for adults.
Most of these examinations take a relatively long time and require a high level
of concentration. Therefore, the aim of the current study was to evaluate an odor
discrimination and olfactory threshold test using the frequently used "Sniffin'
Sticks" in children and adolescents in a simplified two-alternative-forced-choice
version (2AFC) and compare it to the original three-alternative-forced-choice
test (3AFC). One-hundred-twenty-one healthy participants aged between 5 and 17
years took part in this study. Within each of the two sessions participants
underwent olfactory testing using the modified 2AFC as well as the standard 3AFC
method. A better test-retest reliability was achieved using the original 3AFC
method compared to the modified 2AFC. This was true for the odor discrimination
as well as the olfactory threshold. Age had a significant influence on both
tests, which should be considered when testing young children. We discuss these
findings with relation to the existing norms and recommend using the 3AFC version
due to a better test-retest reliability to measure olfactory function in
children.
PMID- 28512303
TI - Volunteer Participation in the Health eHeart Study: A Comparison with the US
Population.
AB - Direct volunteer "eCohort" recruitment can be an efficient way of recruiting
large numbers of participants, but there is potential for volunteer bias. We
compared self-selected participants in the Health eHeart Study to participants in
the National Health And Nutrition Examination Survey (NHANES) 2013-14, a cross
sectional survey of the US population. Compared with the US population
(represented by 5,769 NHANES participants), the 12,280 Health eHeart participants
with complete survey data were more likely to be female (adjusted odds ratio
(ORadj) = 3.1; 95% confidence interval (CI) 2.9-3.5); less likely to be Black,
Hispanic, or Asian versus White/non-Hispanic (ORadj's = 0.4-0.6, p < 0.01); more
likely to be college-educated (ORadj = 15.8 (13-19) versus <=high school); more
likely to have cardiovascular diseases and risk factors (ORadj's = 1.1-2.8, p <
0.05) except diabetes (ORadj = 0.8 (0.7-0.9); more likely to be in excellent
general health (ORadj = 0.6 (0.5-0.8) for "Good" versus "Excellent"); and less
likely to be current smokers (ORadj = 0.3 (0.3-0.4)). While most self-selection
patterns held for Health eHeart users of Bluetooth blood pressure cuff
technology, there were some striking differences; for example, the gender ratio
was reversed (ORadj = 0.6 (0.4-0.7) for female gender). Volunteer participation
in this cardiovascular health-focused eCohort was not uniform among US adults nor
for different components of the study.
PMID- 28512304
TI - Nearly Perfect Durable Superhydrophobic Surfaces Fabricated by a Simple One-Step
Plasma Treatment.
AB - Fabrication of superhydrophobic surfaces is an area of great interest because it
can be applicable to various engineering fields. A simple, safe and inexpensive
fabrication process is required to fabricate applicable superhydrophobic
surfaces. In this study, we developed a facile fabrication method of nearly
perfect superhydrophobic surfaces through plasma treatment with argon and oxygen
gases. A polytetrafluoroethylene (PTFE) sheet was selected as a substrate
material. We optimized the fabrication parameters to produce superhydrophobic
surfaces of superior performance using the Taguchi method. The contact angle of
the pristine PTFE surface is approximately 111.0 degrees +/- 2.4 degrees , with
a sliding angle of 12.3 degrees +/- 6.4 degrees . After the plasma treatment,
nano-sized spherical tips, which looked like crown-structures, were created. This
PTFE sheet exhibits the maximum contact angle of 178.9 degrees , with a sliding
angle less than 1 degrees . As a result, this superhydrophobic surface requires a
small external force to detach water droplets dripped on the surface. The contact
angle of the fabricated superhydrophobic surface is almost retained, even after
performing an air-aging test for 80 days and a droplet impacting test for 6 h.
This fabrication method can provide superb superhydrophobic surface using simple
one-step plasma etching.
PMID- 28512306
TI - Structure Based docking studies towards exploring potential anti-androgen
activity of selected phytochemicals against Prostate Cancer.
AB - Prostate cancer (PCa) is the second most common malignancy amongst men worldwide.
Under PCa maintenance therapy drugs acting as antagonists/partial agonists of
hormone receptors against the prostate tissue are used in clinical practices.
Prominent drugs being Cyproterone acetate, Flutamide, Bicalutamide, they not only
cause acute and long-term toxicity, but also develops drug resistance among
patients. Our focus has been on phytochemicals which do not exhibit any
cytotoxicity and have significant androgen receptor (AR) inhibition activity. As
Protein- Ligand interactions play a key role in structure based drug design, so
by using molecular docking, we screened 803 phytochemicals and investigated their
binding affinity against AR. The three dimensional (3D) structure of AR was
retrieved from Protein Data Bank, and docked with 3D Pubchem structures of 803
phytochemicals using Argus Lab. Molecular docking and drug likeness studies were
made using ADMET properties while Lipinski's rule of five was performed for the
phytochemicals to evaluate their anti-prostate cancer activity. The results
showed that Isobavachin exhibited best binding affinity of -13.73 kcal/mol with
AR followed by Glabranin, Anthocyanin and Eriosemation. Our studies therefore
reveal that these four phytochemicals could be promising candidates for further
evaluation for PCa prevention or management.
PMID- 28512305
TI - Mutation screening in genes known to be responsible for Retinitis Pigmentosa in
98 Small Han Chinese Families.
AB - Retinitis pigmentosa (RP) is highly heterogeneous in both clinical and genetic
fields. Accurate mutation screening is very beneficial in improving clinical
diagnosis and gene-specific treatment of RP patients. The reason for the
difficulties in genetic diagnosis of RP is that the ethnic-specific mutation
databases that contain both clinical and genetic information are largely
insufficient. In this study, we recruited 98 small Han Chinese families
clinically diagnosed as RP, including of 22 dominant, 19 recessive, 52 sporadic,
and five X-linked. We then used whole exome sequencing (WES) analysis to detect
mutations in the genes known for RP in 101 samples from these 98 families. In
total, we identified 57 potential pathogenic mutations in 40 of the 98 (41%)
families in 22 known RP genes, including 45 novel mutations. We detected
mutations in 13 of the 22 (59%) typical autosomal dominant families, 8 of the 19
(42%) typical autosomal recessive families, 16 of the 52 (31%) sporadic small
families, and four of the five (80%) X-linked families. Our results extended the
mutation spectrum of known RP genes in Han Chinese, thus making a contribution to
RP gene diagnosis and the pathogenetic study of RP genes.
PMID- 28512307
TI - Comparing the Success Rate of Dacryocystorhinostomy With and Without Silicone
Intubation: A Trial Sequential Analysis of Randomized Control Trials.
AB - A previous meta-analysis reported no benefit for silicone intubation during
dacryocystorhinostomy. However, the power of this meta-analysis was 0.274.
Therefore, the benefit of silicone intubation remains controversial. We undertook
a cumulative meta-analysis to evaluate the success rate of dacryocystorhinostomy
(DCR) with and without the use of a stent. Pubmed, EMBASE and the Cochrane
Library were searched. Statistical power and trial sequential analyses were
performed according to the result of the meta-analysis. Twelve randomized
controlled trials involving 969 cases met the inclusion criteria. The success
rates of DCR with and without intubation were significantly different (p =
0.006). The success rates of external DCR (EX-DCR) with and without intubation
were also significantly different based on subgroup analysis (p = 0.002). The
cumulative z-curves crossed the O'Brian-Fleming boundaries. There were no
significant differences in the success rate in the endonasal endoscopic DCR (EN
DCR) subgroup or the occurrence of postoperative complications between the two
groups based on the meta-analysis, and the z-curve did not intersect any trial
sequential analysis boundaries. DCR with intubation achieved better results than
DCR without intubation, especially in the EX-DCR subgroup. Differences in the
success rate in the EN-DCR subgroup and postoperative complications between the
two groups were underpowered to reach a conclusion.
PMID- 28512308
TI - Quantum key distribution with hacking countermeasures and long term field trial.
AB - Quantum key distribution's (QKD's) central and unique claim is information
theoretic security. However there is an increasing understanding that the
security of a QKD system relies not only on theoretical security proofs, but also
on how closely the physical system matches the theoretical models and prevents
attacks due to discrepancies. These side channel or hacking attacks exploit
physical devices which do not necessarily behave precisely as the theory expects.
As such there is a need for QKD systems to be demonstrated to provide security
both in the theoretical and physical implementation. We report here a QKD system
designed with this goal in mind, providing a more resilient target against
possible hacking attacks including Trojan horse, detector blinding, phase
randomisation and photon number splitting attacks. The QKD system was installed
into a 45 km link of a metropolitan telecom network for a 2.5 month period,
during which time the system operated continuously and distributed 1.33 Tbits of
secure key data with a stable secure key rate over 200 kbit/s. In addition
security is demonstrated against coherent attacks that are more general than the
collective class of attacks usually considered.
PMID- 28512309
TI - Triplet Cooper pairs induced in diffusive s-wave superconductors interfaced with
strongly spin-polarized magnetic insulators or half-metallic ferromagnets.
AB - Interfacing superconductors with strongly spin-polarized magnetic materials opens
the possibility to discover new spintronic devices in which spin-triplet Cooper
pairs play a key role. Motivated by the recent derivation of spin-polarized
quasiclassical boundary conditions capable of describing such a scenario in the
diffusive limit, we consider the emergent physics in hybrid structures comprised
of a conventional s-wave superconductor (e.g. Nb, Al) and either strongly spin
polarized ferromagnetic insulators (e.g. EuO, GdN) or halfmetallic ferromagnets
(e.g. CrO2, LCMO). In contrast to most previous works, we focus on how the
superconductor itself is influenced by the proximity effect, and how the
generated triplet Cooper pairs manifest themselves in the self-consistently
computed density of states (DOS) and the superconducting critical temperature T c
. We provide a comprehensive treatment of how the superconductor and its
properties are affected by the triplet pairs, demonstrating that our theory can
reproduce the recent observation of an unusually large zero-energy peak in a
superconductor interfaced with a half-metal, which even exceeds the normal-state
DOS. We also discuss the recent observation of a large superconducting spin-valve
effect with a T c change ~1 K in superconductor/half-metal structures, in which
case our results indicate that the experiment cannot be explained fully by a long
ranged triplet proximity effect.
PMID- 28512311
TI - Dramatic improvement of strain hardening and ductility to 95% in highly
deformable high-strength duplex lightweight steels.
AB - Ferrite + austenite duplex lightweight steels have been actively developed by
adding low-density Al for overcoming a limitation of stiffness deterioration by a
traditional approach to obtain a weight reduction. Multiple-stage deformation
mechanism in lightweight steels, i.e., simultaneous formation of deformation
induced martensite and deformation twin and additional plasticity by twinning,
has been nominated as an attractive strategy, but shows a steady flow behavior
with early plastic instability. Here, we present a newly designed Fe-0.3C-9Mn-5Al
steel in order to obtain an optimal level of stability of austenite and a
resultant outstanding combination of tensile strength and ductility, e.g., 874
MPa and 72%, together with sufficiently high strain hardening. These enhanced
properties are attributed to the decreased austenite stability by controlling the
austenite size and alloying partitioning due to variation in austenite fraction
inside duplex microstructures. The present work gives a promise for structural
applications requiring both reduced specific weight and remarkable deformability.
PMID- 28512310
TI - FGF23/FGFR4-mediated left ventricular hypertrophy is reversible.
AB - Fibroblast growth factor (FGF) 23 is a phosphaturic hormone that directly targets
cardiac myocytes via FGF receptor (FGFR) 4 thereby inducing hypertrophic myocyte
growth and the development of left ventricular hypertrophy (LVH) in rodents.
Serum FGF23 levels are highly elevated in patients with chronic kidney disease
(CKD), and it is likely that FGF23 directly contributes to the high rates of LVH
and cardiac death in CKD. It is currently unknown if the cardiac effects of FGF23
are solely pathological, or if they potentially can be reversed. Here, we report
that FGF23-induced cardiac hypertrophy is reversible in vitro and in vivo upon
removal of the hypertrophic stimulus. Specific blockade of FGFR4 attenuates
established LVH in the 5/6 nephrectomy rat model of CKD. Since CKD mimics a form
of accelerated cardiovascular aging, we also studied age-related cardiac
remodeling. We show that aging mice lacking FGFR4 are protected from LVH.
Finally, FGF23 increases cardiac contractility via FGFR4, while known effects of
FGF23 on aortic relaxation do not require FGFR4. Taken together, our data
highlight a role of FGF23/FGFR4 signaling in the regulation of cardiac remodeling
and function, and indicate that pharmacological interference with cardiac
FGF23/FGFR4 signaling might protect from CKD- and age-related LVH.
PMID- 28512312
TI - Two-step phase shifting differential-recording digital holographic microscopy.
AB - We present two-step phase-shifting differential-recording digital holographic
microscopy (TPD-DH in microscopy) for phase imaging of microscopic transparent
elements. Two CCDs are employed to record two interferograms at two different
defocusing distances. The interferograms on the two CCD cameras are shifted for a
phase retarder 0 and pi via an all-optics phase shifting unit. A novel algorithm
is proposed to reconstruct both amplitude and phase distributions of the object
wave from the recorded interferograms. This method has the same spectrum
bandwidth and measurement accuracy with those of conventional four-step phase
shifting interferometry (FS-PSI), whereas it reduces the measurement time by
half.
PMID- 28512313
TI - A Rapid Capillary-Pressure Driven Micro-Channel to Demonstrate Newtonian Fluid
Behavior of Zebrafish Blood at High Shear Rates.
AB - Blood viscosity provides the rheological basis to elucidate shear stress
underlying developmental cardiac mechanics and physiology. Zebrafish is a high
throughput model for developmental biology, forward-genetics, and drug discovery.
The micro-scale posed an experimental challenge to measure blood viscosity. To
address this challenge, a microfluidic viscometer driven by surface tension was
developed to reduce the sample volume required (3MUL) for rapid (<2 min) and
continuous viscosity measurement. By fitting the power-law fluid model to the
travel distance of blood through the micro-channel as a function of time and
channel configuration, the experimentally acquired blood viscosity was compared
with a vacuum-driven capillary viscometer at high shear rates (>500 s-1), at
which the power law exponent (n) of zebrafish blood was nearly 1 behaving as a
Newtonian fluid. The measured values of whole blood from the micro-channel
(4.17cP) and the vacuum method (4.22cP) at 500 s-1 were closely correlated at 27
degrees C. A calibration curve was established for viscosity as a function of
hematocrits to predict a rise and fall in viscosity during embryonic development.
Thus, our rapid capillary pressure-driven micro-channel revealed the Newtonian
fluid behavior of zebrafish blood at high shear rates and the dynamic viscosity
during development.
PMID- 28512314
TI - Water-Assisted Synthesis of Molybdenum Disulfide Film with Single Organic Liquid
Precursor.
AB - We report on the synthesis of large-area molybdenum disulfide (MoS2) film on an
insulating substrate by means of chemical vapor deposition. A single mixture of
molybdenum hexacarbonyl (Mo(CO)6) and dimethyl disulfide (C2H6S2) was utilized as
an organic liquid precursor for the synthesis of MoS2 film. Carbon impurities
stemming from the dissociation of the organic precursor are effectively removed
by water oxidation, and hydrogen gas, which is a by-product of the oxidation of
carbon impurities, inhibits the formation of molybdenum oxides. The use of a
liquid precursor assisted with water oxidation ensures high reproducibility and
full-coverage of MoS2 film for large area, which is not typically achieved with
solid precursors such as molybdenum oxide and sulfur powder. We believe that our
approach will advance the synthesis of transition metal dichalcogenides.
PMID- 28512315
TI - Midgut bacteria in deltamethrin-resistant, deltamethrin-susceptible, and field
caught populations of Plutella xylostella, and phenomics of the predominant
midgut bacterium Enterococcus mundtii.
AB - Gut bacteria play a significant role in host insect. This study evaluated detail
difference of midgut bacteria in deltamethrin-resistant, deltamethrin-susceptible
and field-caught populations of diamondback moth, and studied phenomics of the
predominant midgut bacterium Enterococcus mundtii. Cultivable bacteria revealed
that E. mundtii and Carnobacterium maltaromaticum dominated the bacterial
populations from deltamethrin-resistant and deltamethrin-susceptible larval
midguts, whereas E. mundtii was predominant in field-caught population. Illumina
sequencing analysis indicated that 97% of the midgut bacteria were from the phyla
Firmicutes, Proteobacteria and Cyanobacteria. Both resistant and susceptible
populations had more Enterococcus and Carnobacterium. Enterococcus,
Carnobacterium, Bacillus, and Pseudomonas were predominant in the field-caught
population. A phenomics analysis revealed that E. mundtii was able to metabolize
25.26% of the tested carbon sources, 100% of the nitrogen sources, 100% of the
phosphorus sources and 97.14% of the sulfur sources, had a wide range of
osmolytes and pH conditions, and showed active deaminase activity but no
decarboxylase activity. This is the first report regarding different populations
of DBM midgut bacteria analyzed using both high-throughput DNA sequencing and
cultivation methods, and also first report concerning the phenomics of E.
mundtii. The phenomics of E. mundtii provide a basis for the future study of gut
bacteria functions.
PMID- 28512316
TI - Phenotypic plasticity, trade-offs and gene expression changes accompanying
dietary restriction and switches in Bactrocera dorsalis (Hendel) (Diptera:
Tephritidae).
AB - In this study, we investigated the effects of dietary restriction (DR) and
variable diets on phenotypes and gene expression in oriental fruit fly,
Bactrocera dorsalis (Hendel), one of the most economically important pests in the
family Tephritidae around the world. As expected, we found that DR altered the B.
dorsalis phenotypes by significantly increasing stress resistance and lifespan,
but reduced egg production when compared with the control diet. The results
suggested a trade-off between reproduction versus somatic maintenance (stress
resistance) and lifespan in B. dorsalis. Diet also had a significant effect on
hatchability, and DR could increase the egg hatching success of B. dorsalis.
Furthermore, DR up-regulated metabolic pathways involved in energy homeostasis
and down-regulated pathways in egg production, which might mediate trade-offs
between somatic maintenance and reproduction under DR regimes. The gene
expression profiles in response to the acute dietary switches indicated that the
digestive and metabolic pathways maybe involved in the adaptability of flies to
variable dietary resources. In summary, the research facilitates a better
understanding of the molecular mechanisms responsible for the B. dorsalis'
phenotypic adjustments to the different qualities of the available diets.
PMID- 28512318
TI - Structure-based prediction and identification of 4-epimerization activity of
phosphate sugars in class II aldolases.
AB - Sugar 4-epimerization reactions are important for the production of rare sugars
and their derivatives, which have various potential industrial applications. For
example, the production of tagatose, a functional sweetener, from fructose by
sugar 4-epimerization is currently constrained because a fructose 4-epimerase
does not exist in nature. We found that class II D-fructose-1,6-bisphosphate
aldolase (FbaA) catalyzed the 4-epimerization of D-fructose-6-phosphate (F6P) to
D-tagatose-6-phosphate (T6P) based on the prediction via structural comparisons
with epimerase and molecular docking and the identification of the condensed
products of C3 sugars. In vivo, the 4-epimerization activity of FbaA is normally
repressed. This can be explained by our results showing the catalytic efficiency
of D-fructose-6-phosphate kinase for F6P phosphorylation was significantly higher
than that of FbaA for F6P epimerization. Here, we identified the epimerization
reactions and the responsible catalytic residues through observation of the
reactions of FbaA and L-rhamnulose-1-phosphate aldolases (RhaD) variants with
substituted catalytic residues using different substrates. Moreover, we obtained
detailed potential epimerization reaction mechanism of FbaA and a general
epimerization mechanism of the class II aldolases L-fuculose-1-phosphate
aldolase, RhaD, and FbaA. Thus, class II aldolases can be used as 4-epimerases
for the stereo-selective synthesis of valuable carbohydrates.
PMID- 28512317
TI - Structural determinants of Neosartorya fischeri antifungal protein (NFAP) for
folding, stability and antifungal activity.
AB - The recent global challenges to prevent and treat fungal infections strongly
demand for the development of new antifungal strategies. The structurally very
similar cysteine-rich antifungal proteins from ascomycetes provide a feasible
basis for designing new antifungal molecules. The main structural elements
responsible for folding, stability and antifungal activity are not fully
understood, although this is an essential prerequisite for rational protein
design. In this study, we used the Neosartorya fischeri antifungal protein (NFAP)
to investigate the role of the disulphide bridges, the hydrophobic core, and the
N-terminal amino acids in the formation of a highly stable, folded, and
antifungal active protein. NFAP and its mutants carrying cysteine deletion
(NFAPDeltaC), hydrophobic core deletion (NFAPDeltah), and N-terminal amino acids
exchanges (NFAPDeltaN) were produced in Pichia pastoris. The recombinant NFAP
showed the same features in structure, folding, stability and activity as the
native protein. The data acquired with mass spectrometry, structural analyses and
antifungal activity assays of NFAP and its mutants proved the importance of the
disulphide bonding, the hydrophobic core and the correct N-terminus for folding,
stability and full antifungal function. Our findings provide further support to
the comprehensive understanding of the structure-function relationship in members
of this protein group.
PMID- 28512319
TI - What the skull and scapular morphology of the dugong (Dugong dugon) can tell us:
sex, habitat and body length?
AB - The dugong (Dugong dugon, Muller) is an endangered marine mammal species. We
examined the relationship between sex, habitat and body length based on the skull
and scapular morphology and morphometrics of 81 dugong samples in Thailand. A
total of 58 parameters from the skull and scapula (25 from the cranium, 23 from
the mandible and 10 from the scapula) as well as tusks were used in this study.
Data were analyzed by univariate analysis, followed by discriminant analysis and
multivariate linear regression. Here we show, 100% and 98.5% accuracy rates for
sexing using large tusks and the skull, respectively. Scapular morphology using
the caudal border tubercle and coracoid process showed 91.30% and 96.15% accuracy
rates for identifying males and females. Skull morphometrics could categorize
dugong habitat, i.e. living in the Andaman Sea or Gulf of Thailand, with 100%
accuracy. Moreover, our model could be used to estimate body length with
coefficient of determination (R 2) of 0.985. The results of our study showed that
skull morphology and morphometric measurements could be used as a tool for sex
identification, location identification and estimation of body length. But
scapular morphology is the best tool for sex identification in dugongs.
PMID- 28512320
TI - Hyponatremia upon presentation to the emergency department - the need for urgent
neuroimaging studies.
AB - This study aims to evaluate the necessity of urgent neuroimaging for emergency
admissions exhibiting symptomatology of profound hyponatremia. We retrospectively
analyzed the medical records of all patients admitted to the emergency room of
the University Hospital Munster from 2010 to 2014 with a serum sodium value < 125
mmol/L. From 52918 emergency admissions, 261 patients with profound hyponatremia
were identified, of whom 140 (54%) had neurological symptoms. Unspecific weakness
and confusion were the most prevalent of these symptoms (59%). Focal neurological
signs [FNS] were present in 31% of cases and neuroimaging was performed in 68%
(95/140) of symptomatic patients. Multiple logistic regression analysis
identified FNS, seizures, altered consciousness and age as independent predictors
for conducting neuroimaging (all p < 0.05). Significant pathological findings
consistent with acute symptomatology were evident in 17 cases, all of whom had
FNS. Recursive partitioning analyses confirmed FNS as the best predictor of
neuroimaging pathology (p < 0.001). Absence of FNS had a negative predictive
value of 100% [95% confidence interval: 93-100%] for excluding neuroimaging
pathology. In conclusion, emergency patients with profound hyponatremia
frequently show nonspecific-neurological symptoms and may undergo neuroimaging
unnecessarily. The lack of FNS may serve as a valuable criterion for withholding
neuroimaging until hyponatremia has been corrected.
PMID- 28512321
TI - Restoration of the growth of Escherichia coli under K+-deficient conditions by
Cs+ incorporation via the K+ transporter Kup.
AB - Biological incorporation of cesium ions (Cs+) has recently attracted significant
attention in terms of the possible applications for bioremediation of radiocesium
and their significant roles in biogeochemical cycling. Although high
concentrations of Cs+ exhibit cytotoxicity on microorganisms, there are a few
reports on the promotive effects of Cs+ on microbial growth under K+-deficient
conditions. However, whether this growth-promoting effect is a common phenomenon
remains uncertain, and direct correlation between growth promotion and Cs+ uptake
abilities has not been confirmed yet. Here, we validated the growth promotive
effects of Cs+ uptake under K+-deficient conditions using an Escherichia coli
strain with an inducible expression of the Kup K+ transporter that has
nonspecific Cs+ transport activities (strain kup-IE). The strain kup-IE exhibited
superior growth under the Cs+-supplemented and K+-deficient conditions compared
to the wild type and the kup null strains. The intracellular Cs+ levels were
significantly higher in strain kup-IE than in the other strains, and were well
correlated with their growth yields. Furthermore, induction levels of the kup
gene, intracellular Cs+ concentrations, and the growth stimulation by Cs+ also
correlated positively. These results clearly demonstrated that Cs+ incorporation
via Kup transporter restores growth defects of E. coli under K+-deficient
conditions.
PMID- 28512323
TI - Nicotine in floral nectar pharmacologically influences bumblebee learning of
floral features.
AB - Many plants defend themselves against herbivores by chemical deterrents in their
tissues and the presence of such substances in floral nectar means that
pollinators often encounter them when foraging. The effect of such substances on
the foraging behaviour of pollinators is poorly understood. Using artificial
flowers in tightly-controlled laboratory settings, we examined the effects of the
alkaloid nicotine on bumblebee foraging performance. We found that bumblebees
confronted simultaneously with two equally rewarded nicotine-containing and
nicotine-free flower types are deterred only by unnaturally high nicotine
concentrations. This deterrence disappears or even turns into attraction at lower
nectar-relevant concentrations. The alkaloid has profound effects on learning in
a dose-dependent manner. At a high natural dose, bees learn the colour of a
nicotine-containing flower type more swiftly than a flower type with the same
caloric value but without nicotine. Furthermore, after experiencing flowers
containing nicotine in any tested concentration, increasing numbers of bumblebees
stay more faithful to these flowers, even if they become a suboptimal choice in
terms of reward. These results demonstrate that alkaloids enhance pollinator
flower constancy, opening new perspectives in co-evolutionary process between
plants and pollinators.
PMID- 28512325
TI - Complex hierarchical microstructures of Cambrian mollusk Pelagiella: insight into
early biomineralization and evolution.
AB - Shell microstructure and mineralogy of Pelagiella madianensis Zhou & Xiao, 1984,
a globally distributed Cambrian micromollusk, are investigated based on abundant
and extraordinarily well-preserved specimens from Xinji Formation, Longxian,
Shaanxi, North China. Five types of aragonitic microstructures have been
recognized. The lamello-fibrillar microstructure, previously known from
Pelagiella, constructs the outermost shell layer, while the remaining four types
are reported here for the first time in this genus. They include fibrous
foliated, foliated aragonite, crossed foliated lamellar and isolated tablets. The
animal constructs these five types of microstructures to build its shell in a
complex hierarchical pattern with four orders: crystallite columns, laths, folia
and lamellae. These findings demonstrate that the capability of building complex
shell microstructures had already evolved by the Cambrian explosion. In addition,
this work shows that early aragonitic shells were constructed with fibers, laths,
folia and isolated tablets, indicating increased controls over biomineralization
by the animal.
PMID- 28512324
TI - Global gene expression analysis provides insight into local adaptation to
geothermal streams in tadpoles of the Andean toad Rhinella spinulosa.
AB - The anuran Rhinella spinulosa is distributed along the Andes Range at altitudes
that undergo wide daily and seasonal variation in temperature. One of the
populations inhabits geothermal streams, a stable environment that influences
life history traits such as the timing of metamorphosis. To investigate whether
this population has undergone local adaptation to this unique habitat, we carried
out transcriptome analyses in animals from two localities in two developmental
stages (prometamorphic and metamorphic) and exposed them to two temperatures (20
and 25 degrees C). RNA-Seq, de novo assembly and annotation defined a
transcriptome revealing 194,469 high quality SNPs, with 1,507 genes under
positive selection. Comparisons among the experimental conditions yielded 1,593
differentially expressed genes. A bioinformatics search for candidates revealed a
total of 70 genes that are highly likely to be implicated in the adaptive
response of the population living in a stable environment, compared to those
living in an environment with variable temperatures. Most importantly, the
population inhabiting the geothermal environment showed decreased transcriptional
plasticity and reduced genetic variation compared to its counterpart from the non
stable environment. This analysis will help to advance the understanding of the
molecular mechanisms that account for the local adaptation to geothermal streams
in anurans.
PMID- 28512322
TI - Physicochemical properties of dietary phytochemicals can predict their passive
absorption in the human small intestine.
AB - A diet high in phytochemical-rich plant foods is associated with reducing the
risk of chronic diseases such as cardiovascular and neurodegenerative diseases,
obesity, diabetes and cancer. Oxidative stress and inflammation (OSI) is the
common component underlying these chronic diseases. Whilst the positive health
effects of phytochemicals and their metabolites have been demonstrated to
regulate OSI, the timing and absorption for best effect is not well understood.
We developed a model to predict the time to achieve maximal plasma concentration
(Tmax) of phytochemicals in fruits and vegetables. We used a training dataset
containing 67 dietary phytochemicals from 31 clinical studies to develop the
model and validated the model using three independent datasets comprising a total
of 108 dietary phytochemicals and 98 pharmaceutical compounds. The developed
model based on dietary intake forms and the physicochemical properties
lipophilicity and molecular mass accurately predicts Tmax of dietary
phytochemicals and pharmaceutical compounds over a broad range of chemical
classes. This is the first direct model to predict Tmax of dietary phytochemicals
in the human body. The model informs the clinical dosing frequency for optimising
uptake and sustained presence of dietary phytochemicals in circulation, to
maximise their bio-efficacy for positively affect human health and managing OSI
in chronic diseases.
PMID- 28512327
TI - Prognostic value of hypoalbuminemia for adverse outcomes in patients with
rheumatic heart disease undergoing valve replacement surgery.
AB - High-risk patients with rheumatic heart disease (RHD) who were undergoing valve
replacement surgery (VRS) were not identified entirely. This study included 1782
consecutive patients with RHD who were undergoing VRS to explore the relationship
between hypoalbuminemia and adverse outcomes and to confirm whether
hypoalbuminemia plays a role in risk evaluation. A total of 27.3% of the RHD
patients had hypoalbuminemia. In-hospital deaths were significantly higher in the
hypoalbuminemic group than in the non-hypoalbuminemic group (6.6% vs 3.1%, P =
0.001). Hypoalbuminemia was an independent predictor of in-hospital death (OR =
1.89, P = 0.014), even after adjusting for the Euro score. The addition of
hypoalbuminemia to Euro score enhanced net reclassification improvement (0.346
for in-hospital death, P = 0.004; 0.306 for 1-year death, p = 0.005). A Kaplan
Meier curve analysis revealed that the cumulative rate of 1-year mortality after
the operation was higher in patients with a new Euro score >=6. These findings
indicated that hypoalbuminemia was an independent risk factor for in-hospital and
1-year mortality after VRS in patients with RHD, which might have additive
prognostic value to Euro score.
PMID- 28512326
TI - Accuracy of shear wave elastography for the diagnosis of prostate cancer: A meta
analysis.
AB - Many studies have established the high diagnostic accuracy of shear wave
elastography (SWE) for the detection of prostate cancer (PCa); however, its
utility remains a subject of debate. This meta-analysis sought to appraise the
overall accuracy of SWE for the detection of PCa. A literature search of the
PubMed, Embase, Cochrane Library, Web of Science and CNKI (China National
Knowledge Infrastructure) databases was conducted. In all of the included
studies, the diagnostic accuracy of SWE was compared with that of histopathology,
which was used as a standard. Data were pooled, and the sensitivity, specificity,
area under the curve (AUC), positive likelihood ratio (PLR), negative likelihood
ratio (NLR), and diagnostic odds ratio (DOR) were calculated to estimate the
accuracy of SWE. The pooled sensitivity and specificity for the diagnosis of PCa
by SWE were 0.844 (95% confidence interval: 0.696-0.927) and 0.860 (0.792-0.908),
respectively. The AUC was 0.91 (0.89-0.94), the PLR was 6.017 (3.674-9.853), and
the NLR was 0.182 (0.085-0.389). The DOR was 33.069 (10.222-106.982). Thus, SWE
exhibited high accuracy for the detection of PCa using histopathology as a
diagnostic standard. Moreover, SWE may reduce the number of core biopsies needed.
PMID- 28512328
TI - Tacrolimus Blood Level Fluctuation Predisposes to Coexisting BK Virus Nephropathy
and Acute Allograft Rejection.
AB - BK virus nephropathy (BKVN) and allograft rejection are two distinct disease
entities which occur at opposite ends of the immune spectrum. However, they
coexist in renal transplant recipients. Predisposing factors for this coexistence
remain elusive. We identified nine biopsy-proven BKVN patients with coexisting
acute rejection, and 21 patients with BKVN alone. We retrospectively analyzed the
dosage and blood concentrations of immunosuppressants during the 3-month period
prior to the renal biopsy between the two patient groups. Compared to the BKVN
alone group, renal function was noticeably worse in the coexistence group (p =
0.030). Regarding the dose and average drug level of immunosuppressants, there
was no difference between the two groups. Interestingly, the coefficient of
variance of tacrolimus trough blood level was noticeably higher during the 3
month period prior to the renal biopsy in the coexistence group (p = 0.010). Our
novel findings suggest that a higher variability of tacrolimus trough level may
be associated with the coexistence of BKVN and acute rejection. Since the
prognosis is poor and the treatment is challenging in patients with coexisting
BKVN and acute rejection, transplant clinicians should strive to avoid
fluctuations in immunosuppressant drug levels in patients with either one of
these two disease entities.
PMID- 28512329
TI - Tree-ring widths are good proxies of annual variation in forest productivity in
temperate forests.
AB - Tree rings have long been used to calibrate the net primary production (NPP) time
series predicted by process-based models, based on an implicit assumption that
ring-width indices (RWI) can well reflect temporal NPP change. However, this
assumption has seldom been tested systematically. In this study, 36 plots were
set in three forest types from four sites along a latitudinal gradient in
northeast China. For each plot, we constructed chronologies and stand NPP of the
past 20 years to examine: is RWI a good proxy of inter-annual variation of forest
NPP for different forest types under different climate? If it is, why? Our
results indicate that RWI was closely related to stand NPP in most cases, and
could be used as a good proxy of NPP in temperate forests. Standard and arstan
chronologies were better related to NPP series than residual chronology. Stand
NPP time-series were mainly determined by large trees, and the correlation
between RWI and NPP was also higher for larger trees. We suggest that large trees
and dominant species of canopy layer should be sampled for chronology
construction. Large trees are major contributors of forest biomass and
productivity, and should have priority in forest conservation in a rapid-warming
world.
PMID- 28512330
TI - Direct evaluation of influence of electron damage on the subcell performance in
triple-junction solar cells using photoluminescence decays.
AB - Tandem solar cells are suited for space applications due to their high
performance, but also have to be designed in such a way to minimize influence of
degradation by the high energy particle flux in space. The analysis of the
subcell performance is crucial to understand the device physics and achieve
optimized designs of tandem solar cells. Here, the radiation-induced damage of
inverted grown InGaP/GaAs/InGaAs triple-junction solar cells for various electron
fluences are characterized using conventional current-voltage (I-V) measurements
and time-resolved photoluminescence (PL). The conversion efficiencies of the
entire device before and after damage are measured with I-V curves and compared
with the efficiencies predicted from the time-resolved method. Using the time
resolved data the change in the carrier dynamics in the subcells can be
discussed. Our optical method allows to predict the absolute electrical
conversion efficiency of the device with an accuracy of better than 5%. While
both InGaP and GaAs subcells suffered from significant material degradation, the
performance loss of the total device can be completely ascribed to the damage in
the GaAs subcell. This points out the importance of high internal electric fields
at the operating point.
PMID- 28512331
TI - Entanglement concentration for arbitrary four-particle linear cluster states.
AB - Cluster states, whose model are a remarkably rich structure in measurement-based
quantum computation, hold high degree of entanglement, while entanglement is very
fragile during the process of transmission because of the inevitable interaction
with the environment. We propose two entanglement concentration protocols for
four-particle linear cluster states which and are susceptible to the decoherence
and the imperfect communication setups. In the first protocol, POVM operators are
introduced to maximize the success probability, and the second protocol is based
on cross-Kerr nonlinearity which is utilized to check the parity between the
original particle and the ancillary particle. Both of the protocols have their
own advantages. The first one can be easily realized in experiment by linear
optics, while the one with cross-Kerr nonlinearity reach more than 90% success
probability by iteration. Since the wide application of cluster states, the two
protocols are efficient and valuable to different fields of quantum
communication.
PMID- 28512332
TI - Microalgal diversity fosters stable biomass productivity in open ponds treating
wastewater.
AB - It is established that biodiversity determines productivity of natural ecosystems
globally. We have proved that abiotic factors influenced biomass productivity in
engineered ecosystems i.e. high rate algal ponds (HRAPs), previously. This study
demonstrates that biotic factors, particularly microalgal diversity, play an
essential role in maintaining stable biomass productivity in HRAP treating
municipal wastewater by mutualistic adaptation to environmental factors. The
current study examined data from the second year of a two-year study on HRAP
treating municipal wastewater. Microalgal diversity, wastewater characteristics,
treatment efficiency and several environmental and meteorological factors were
documented. Multivariate statistical analyses reveal that microalgae in
uncontrolled HRAPs adapt to adverse environmental conditions by fostering
diversity. Subsequently, five dominant microalgal strains by biovolume were
isolated, enriched, and optimum conditions for high biomass productivity were
ascertained. These laboratory experiments revealed that different microalgal
strains dominate in different conditions and a consortium of these diverse taxa
help in sustaining the algae community from environmental and predatory
pressures. Diversity, niche or seasonal partitioning and mutualistic growth are
pertinent in microalgal cultivation or wastewater treatment. Therefore,
enrichment of selective species would deprive the collective adaptive ability of
the consortium and encourage system vulnerability especially in wastewater
treatment.
PMID- 28512333
TI - Hybrid Organic Tandem Solar Cell Comprising Small-Molecule Bottom and
Polymer:Fullerene Top Subcells Fabricated by Thin-Film Transfer.
AB - Multilayer structures involving solution-deposited polymer films are difficult to
fabricate, not allowing for unrestricted designs of polymer-based optoelectronic
devices required for maximizing their performance. Here, we fabricate a hybrid
organic tandem solar cell whose top and bottom subcells have polymer:fullerene
and small molecules active layers, respectively, by a solvent-free process based
on transferring the polymer:fullerene layer from an elastomeric stamp onto a
vacuum-deposited bottom subcell. The interface between small-molecule and
transferred polymer:fullerene layers is void-free at the nanoscale, allowing for
efficient charge transport across the interface. Consequently, the transfer
fabricated tandem cell has an open-circuit voltage (V OC) almost identical to the
sum of V OC values for the single-junction devices. The short-circuit current
density (J SC) of the tandem cell is maximized by current matching achieved by
varying the thickness of the small-molecule active layer in the bottom subcell,
which is verified by numerical simulations. The optimized transfer-fabricated
tandem cell, whose active layers are composed of poly[2,1,3-benzothiadiazole-4,7
diyl[4,4-bis(2-ethylhexyl)-4H-cyclopenta[2,1-b:3,4-b']dithiophene-2,6
diyl]]:[6,6]-Phenyl-C71-butyric acid methyl ester and Di-[4-(N,N-di-p-tolyl
amino)-phenyl]cyclohexane:C70, has V OC = 1.46 V, J SC = 8.48 mA/cm2, a fill
factor of 0.51, leading to the power-conversion efficiency of 6.26%, the highest
among small molecule-polymer:fullerene hybrid tandem solar cells demonstrated so
far.
PMID- 28512334
TI - Three-dimensional scoring of zebrafish behavior unveils biological phenomena
hidden by two-dimensional analyses.
AB - The study of zebrafish behavior represents a cornerstone upon which basic
researchers promise to advance knowledge in life sciences. Although zebrafish
swim in a three-dimensional (3D) space, their behavior in the lab is almost
exclusively scored in two dimensions, whereby zebrafish are recorded using a
single camera providing 2D videos. Whether this dimensional reduction preserves
the reliability of data has not been addressed. Here we show that, compared to a
3D observation, 2D data are flawed by over-reporting and under-reporting of
locomotory differences. Specifically, we first reconstructed 3D trajectories
through the integration of synchronous information derived from two cameras, and
then compared them with the original 2D views in classical experimental paradigms
assessing shoaling tendency, fear, anxiety, and general locomotion. Our results
suggest that traditional behavioral scoring of individual zebrafish performed in
2D may undermine data integrity, thereby requiring a general reconsideration of
scoring zebrafish behavior to incorporate a 3D approach. We then demonstrate
that, compared to 2D, a 3D approach requires a reduced number of subjects to
achieve the same degree of validity. We anticipate these findings to largely
benefit animal welfare by reducing the number of experimental subjects, without
affecting statistical power.
PMID- 28512335
TI - Arginine-rich cell-penetrating peptide-modified extracellular vesicles for active
macropinocytosis induction and efficient intracellular delivery.
AB - Extracellular vesicles (EVs) including exosomes have been shown to play crucial
roles in cell-to-cell communication because of their ability to carry
biofunctional molecules (e.g., microRNAs and enzymes). EVs also have
pharmaceutical advantages and are highly anticipated to be a next-generation
intracellular delivery tool. Here, we demonstrate an experimental technique that
uses arginine-rich cell-penetrating peptide (CPP)-modified EVs to induce active
macropinocytosis for effective cellular EV uptake. Modification of arginine-rich
CPPs on the EV membrane resulted in the activation of the macropinocytosis
pathway, and the number of arginine residues in the peptide sequences affected
the cellular EV uptake efficiency. Consequently, the ribosome-inactivating
protein saporin-encapsulated EVs modified with hexadeca-arginine (R16) peptide
effectively attained anti-cancer activity.
PMID- 28512337
TI - Powder Metallurgy Processing of a WxTaTiVCr High-Entropy Alloy and Its Derivative
Alloys for Fusion Material Applications.
AB - The WxTaTiVCr high-entropy alloy with 32at.% of tungsten (W) and its derivative
alloys with 42 to 90at.% of W with in-situ TiC were prepared via the mixing of
elemental W, Ta, Ti, V and Cr powders followed by spark plasma sintering for the
development of reduced-activation alloys for fusion plasma-facing materials.
Characterization of the sintered samples revealed a BCC lattice and a multi-phase
structure. The selected-area diffraction patterns confirmed the formation of TiC
in the high-entropy alloy and its derivative alloys. It revealed the development
of C15 (cubic) Laves phases as well in alloys with 71 to 90at.% W. A mechanical
examination of the samples revealed a more than twofold improvement in the
hardness and strength due to solid-solution strengthening and dispersion
strengthening. This study explored the potential of powder metallurgy processing
for the fabrication of a high-entropy alloy and other derived compositions with
enhanced hardness and strength.
PMID- 28512336
TI - Lung Cancer Screening Based on Type-different Sensor Arrays.
AB - In recent years, electronic nose (e-nose) systems have become a focus method for
diagnosing pulmonary diseases such as lung cancer. However, principles and
patterns of sensor responses in traditional e-nose systems are relatively
homogeneous. Less study has been focused on type-different sensor arrays. In this
paper, we designed a miniature e-nose system using 14 gas sensors of four types
and its subsequent analysis of 52 breath samples. To investigate the performance
of this system in identifying and distinguishing lung cancer from other
respiratory diseases and healthy controls, five feature extraction algorithms and
two classifiers were adopted. Lastly, the influence of type-different sensors on
the identification ability of e-nose systems was analyzed. Results indicate that
when using the LDA fuzzy 5-NN classification method, the sensitivity, specificity
and accuracy of discriminating lung cancer patients from healthy controls with e
nose systems are 91.58%, 91.72% and 91.59%, respectively. Our findings also
suggest that type-different sensors could significantly increase the diagnostic
accuracy of e-nose systems. These results showed e-nose system proposed in this
study was potentially practicable in lung cancer screening with a favorable
performance. In addition, it is important for type-different sensors to be
considered when developing e-nose systems.
PMID- 28512339
TI - Nash Equilibrium of Social-Learning Agents in a Restless Multiarmed Bandit Game.
AB - We study a simple model for social-learning agents in a restless multiarmed
bandit (rMAB). The bandit has one good arm that changes to a bad one with a
certain probability. Each agent stochastically selects one of the two methods,
random search (individual learning) or copying information from other agents
(social learning), using which he/she seeks the good arm. Fitness of an agent is
the probability to know the good arm in the steady state of the agent system. In
this model, we explicitly construct the unique Nash equilibrium state and show
that the corresponding strategy for each agent is an evolutionarily stable
strategy (ESS) in the sense of Thomas. It is shown that the fitness of an agent
with ESS is superior to that of an asocial learner when the success probability
of social learning is greater than a threshold determined from the probability of
success of individual learning, the probability of change of state of the rMAB,
and the number of agents. The ESS Nash equilibrium is a solution to Rogers'
paradox.
PMID- 28512338
TI - Impact of metabolic status on the incidence of psoriasis: a Korean nationwide
cohort study.
AB - Growing evidence suggests that obesity is a risk factor for incident psoriasis.
This study was aimed to evaluate the association of obesity and metabolic status
with the incidence of psoriasis. A total of 418,057 adults were followed-up using
a nationwide prospective cohort study in Korea. Participants were stratified
based on the body mass index categories and metabolic condition. During the
follow-up visit, 11054 (2.6%) cases were found to have psoriasis. Diabetes,
hypertension, hyperlipidemia, and obesity were all found to be risk factors for
incident psoriasis. The metabolically unhealthy non-obese (MUNO) subjects (hazard
ratio [HR], 1.29; 95% confidence interval [CI], 1.22-1.37) and metabolically
unhealthy obese subjects (MUO; HR, 1.33; 95% CI, 1. 26-1.41) had a significantly
higher risk of psoriasis incidence as compared to metabolically healthy non-obese
subjects. The risk of psoriasis development was found to be high among the MUNO
and MUO subjects in both sexes and all age groups. In conclusion, the metabolic
health status was significantly associated with an increased risk of psoriasis in
both obese and non-obese individuals. However, further studies are needed to
evaluate whether the control of metabolic parameters can lower the incidence of
psoriasis.
PMID- 28512340
TI - Using an Event-History with Risk-Free Model to Study the Genetics of Alcoholism.
AB - Case-control genetic association studies typically ignore possible later disease
onset in currently healthy subjects and assume that subjects with diseases
equally contribute to the likelihood for inference, regardless of their onset
age. Therefore, we used an event-history with risk-free model to simultaneously
characterize alcoholism susceptibility and onset age in 65 independent non
Hispanic Caucasian males in the Collaborative Study on the Genetics of
Alcoholism. Following data quality control, we analysed 22 single nucleotide
polymorphisms (SNPs) on 12 candidate genes. The single-SNP analysis showed that
the dominant minor allele of rs2134655 on DRD3 increases alcoholism
susceptibility; the dominant minor allele of rs1439047 on NTRK2 delays the
alcoholism onset age, but the additive minor allele of rs172677 on GRIN2B and the
dominant minor allele of rs63319 on ALDH1A1 advance the alcoholism onset age; and
the dominant minor allele of rs1079597 on DRD2 shortens the onset age range.
Similarly, multiple-SNPs analysis revealed joint effects of rs2134655, rs172677
and rs1079597, with an adjustment for habitual smoking. This study provides a
more comprehensive understanding of the genetics of alcoholism than previous case
control studies.
PMID- 28512341
TI - A new paradigm in sweat based wearable diagnostics biosensors using Room
Temperature Ionic Liquids (RTILs).
AB - Successful commercialization of wearable diagnostic sensors necessitates
stability in detection of analytes over prolonged and continuous exposure to
sweat. Challenges are primarily in ensuring target disease specific small
analytes (i.e. metabolites, proteins, etc.) stability in complex sweat buffer
with varying pH levels and composition over time. We present a facile approach to
address these challenges using RTILs with antibody functionalized sensors on
nanoporous, flexible polymer membranes. Temporal studies were performed using
both infrared spectroscopic, dynamic light scattering, and impedimetric
spectroscopy to demonstrate stability in detection of analytes, Interleukin-6 (IL
6) and Cortisol, from human sweat in RTILs. Temporal stability in sensor
performance was performed as follows: (a) detection of target analytes after 0,
24, 48, 96, and 168 hours post-antibody sensor functionalization; and (b)
continuous detection of target analytes post-antibody sensor functionalization.
Limit of detection of IL-6 in human sweat was 0.2 pg/mL for 0-24 hours and 2
pg/mL for 24-48 hours post-antibody sensor functionalization. Continuous
detection of IL-6 over 0.2-200 pg/mL in human sweat was demonstrated for a period
of 10 hours post-antibody sensor functionalization. Furthermore, combinatorial
detection of IL-6 and Cortisol in human sweat was established with minimal cross
talk for 0-48 hours post-antibody sensor functionalization.
PMID- 28512342
TI - A gas sensor array for the simultaneous detection of multiple VOCs.
AB - Air quality around the globe is declining and public health is seriously
threatened by indoor air pollution. Typically, indoor air pollutants are composed
of a series of volatile organic compounds (VOCs) that are generally harmful to
the human body, especially VOCs with low molecular weights (less than 100 Da).
Moreover, in some situations, more than one type of VOC is present; thus, a
device that can detect one or more VOCs simultaneously would be most beneficial.
Here, we synthesized a sensor array with 4 units to detect 4 VOCs: acetone (unit
1), benzene (unit 2), methanol (unit 3) and formaldehyde (unit 4) simultaneously.
All units were simultaneously exposed to 2.5 ppm of all four VOCs. The
sensitivity of unit 1 was 14.67 for acetone and less than 2.54 for the other
VOCs. The sensitivities of units 2, 3 and 4 to benzene, methanol and formaldehyde
were 2 18.64, 20.98 and 17.26, respectively, and less than 4.01 for the other
VOCs. These results indicated that the sensor array exhibited good selectivity
and could be used for the real-time monitoring of indoor air quality. Thus, this
device will be useful in situations requiring the simultaneous detection of
multiple VOCs.
PMID- 28512343
TI - The influence of statistical properties of Fourier coefficients on random
Gaussian surfaces.
AB - Many examples of natural systems can be described by random Gaussian surfaces.
Much can be learned by analyzing the Fourier expansion of the surfaces, from
which it is possible to determine the corresponding Hurst exponent and
consequently establish the presence of scale invariance. We show that this
symmetry is not affected by the distribution of the modulus of the Fourier
coefficients. Furthermore, we investigate the role of the Fourier phases of
random surfaces. In particular, we show how the surface is affected by a non
uniform distribution of phases.
PMID- 28512344
TI - Ecological relevance of skeletal fatty acid concentration and composition in
Mediterranean scleractinian corals.
AB - The intra-skeletal fatty acid concentration and composition of four Mediterranean
coral species, namely Cladocora caespitosa, Balanophyllia europaea, Astroides
calycularis and Leptopsammia pruvoti, were examined in young and old individuals
living in three different locations of the Mediterranean Sea. These species are
characterized by diverse levels of organization (solitary or colonial) and
trophic strategies (symbiotic or non-symbiotic). Fatty acids have manifold
fundamental roles comprehensive of membrane structure fluidity, cell signaling
and energy storage. For all species, except for B. europaea, the intra-skeletal
fatty acid concentration was significantly higher in young individuals than in
old ones. Moreover, fatty acid concentration was higher in colonial corals than
in solitary ones and in the symbiotic corals compared to non-symbiotic ones.
Analysis by gas chromatography-mass spectrometry (GC-MS) revealed that palmitic
acid (16:0) was the most abundant fatty acid, followed by stearic (18:0) in order
of concentration. Oleic acid (18:1) was detected as the third main component only
in skeletons from symbiotic corals. These results suggest that, in the limits of
the studied species, intra-skeletal fatty acid composition and concentration may
be used for specific cases as a proxy of level of organization and trophic
strategy, and eventually coral age.
PMID- 28512345
TI - Phosphoproteome Analysis Reveals Phosphorylation Underpinnings in the Brains of
Nurse and Forager Honeybees (Apis mellifera).
AB - The honeybee brain is a central organ in regulating wide ranges of honeybee
biology, including life transition from nurse to forager bees. Knowledge is still
lacking on how protein phosphorylation governs the neural activity to drive the
age-specific labor division. The cerebral phosphoproteome of nurse and forager
honeybees was characterized using Ti4+-IMAC phosphopeptide enrichment mass
spectrometry-based proteomics and protein kinases (PKs) were predicted. There
were 3,077 phosphosites residing on 3,234 phosphopeptides from 1004
phosphoproteins in the nurse bees. For foragers the numbers were 3,056, 3,110,
and 958, respectively. Notably, among the total 231 PKs in honeybee proteome, 179
novel PKs were predicted in the honeybee brain, of which 88 were experimentally
identified. Proteins involved in wide scenarios of pathways were phosphorylated
depending on age: glycolysis/gluconeogenesis, AGE/RAGE and phosphorylation in
nurse bees and metal ion transport, ATP metabolic process and phototransduction
in forager bees. These observations suggest that phosphorylation is vital to the
tuning of protein activity to regulate cerebral function according to the
biological duties as nursing and foraging bees. The data provides valuable
information on phosphorylation signaling in the honeybee brain and potentially
useful resource to understand the signaling mechanism in honeybee neurobiology
and in other social insects as well.
PMID- 28512346
TI - Cryptic diversity in the Japanese mantis shrimp Oratosquilla oratoria (Crustacea:
Squillidae): Allopatric diversification, secondary contact and hybridization.
AB - Mounting evidence of cryptic species in the marine realm emphasizes the necessity
to thoroughly revise our current perceptions of marine biodiversity and species
distributions. Here, we used mitochondrial cytochrome oxidase subunit I (mtDNA
COI) and nuclear ribosomal internal transcribed spacer (nrDNA ITS) to investigate
cryptic diversity and potential hybridization in the Japanese mantis shrimp
Oratosquilla oratoria in the Northwestern (NW) Pacific. Both mitochondrial and
nuclear gene genealogies revealed two cryptic species in this morphotaxon, which
was further confirmed by extensive population-level analyses. One cryptic species
is restricted to cold waters with a distribution range corresponding to temperate
affinities, while the other dwelled warm waters influenced by the Kuroshio
Current. Their divergence was postulated to be attributable to the vicariant
event which resulted from the isolation of the Sea of Japan during the middle
Pliocene (c. 3.85 Mya, 95% HPD 2.23-6.07 Mya). Allopatric speciation was
maintained by limited genetic exchange due to their habitat preferences.
Furthermore, the observation of recombinant nrDNA ITS sequence and intra
individual ITS polymorphism suggested recent hybridization event of the two
cryptic species occurred in sympatric areas. Our study also illustrated that the
Changjiang River outflow might act as an oceanic barrier to gene flow and
promoted allopatric diversification in O. oratoria species complex.
PMID- 28512347
TI - Insight into the global evolution of Rodentia associated Morbilli-related
paramyxoviruses.
AB - One portion of the family Paramyxoviridae is a group of Unclassified Morbilli
Related Viruses (UMRV) recently recognized in wild small mammals. At a global
level, the evolutionary history of these viruses is not properly understood and
the relationships between UMRV and their hosts still remain largely unstudied.
The present study revealed, for the first time, that Rodentia associated UMRV
emerged from a common ancestor in southern Africa more than 4000 years ago.
Sequenced UMRV originating from different regions in the world, clustered into
four well-supported viral lineages, which suggest that strain diversification
occurred during host dispersal and associated exchanges, with purifying selection
pressure as the principal evolutionary force. In addition, multi-introductions on
different continents and islands of Rodentia associated UMRV and spillover
between rodent species, most probably Rattus rattus, were detected and indicate
that these animals are implicated in the vectoring and in the worldwide emergence
of this virus group. The natural history and the evolution dynamics of these
zoonotic viruses, originating from and hosted by wild animals, are most likely
shaped by commensalism related to human activities.
PMID- 28512348
TI - Adaptive evolution of proteins in hepatitis B virus during divergence of
genotypes.
AB - Hepatitis B virus (HBV) is classified into several genotypes, correlated with
different geographic distributions, clinical outcomes and susceptible human
populations. It is crucial to investigate the evolutionary significance behind
the diversification of HBV genotypes, because it improves our understanding of
their pathological differences and pathogen-host interactions. Here, we performed
comprehensive analysis of HBV genome sequences collected from public database.
With a stringent criteria, we generated a dataset of 2992 HBV genomes from eight
major genotypes. In particular, we applied a specified classification of non
synonymous and synonymous variants in overlapping regions, to distinguish joint
and independent gene evolutions. We confirmed the presence of selective
constraints over non-synonymous variants in consideration of overlapping regions.
We then performed the McDonald-Kreitman test and revealed adaptive evolutions of
non-synonymous variants during genotypic differentiation. Remarkably, we
identified strong positive selection that drove the differentiation of PreS1
domain, which is an essential regulator involved in viral transmission. Our study
presents novel evidences for the adaptive evolution of HBV genotypes, which
suggests that these viruses evolve directionally for maintenance or improvement
of successful infections.
PMID- 28512349
TI - The winding path of protein methylation research: milestones and new frontiers.
AB - In 1959, while analysing the bacterial flagellar proteins, Ambler and Rees
observed an unknown species of amino acid that they eventually identified as
methylated lysine. Over half a century later, protein methylation is known to
have a regulatory role in many essential cellular processes that range from gene
transcription to signal transduction. However, the road to this now burgeoning
research field was obstacle-ridden, not least because of the inconspicuous nature
of the methyl mark itself. Here, we chronicle the milestone achievements and
discuss the future of protein methylation research.
PMID- 28512352
TI - Stem cells: Stem cell-based therapies threatened by the accumulation of p53
mutations.
PMID- 28512353
TI - Favorable Response to Long-term Nucleos(t)ide Analogue Therapy in HBeAg-positive
Patients with High Serum Fucosyl-Agalactosyl IgG.
AB - Aberrant IgG glycosylation is a feature of hepatitis B virus (HBV) infection but
its effect on a long-term efficacy of antiviral therapy has never been addressed.
After a screening of 1,085 patients, 132 eligible HBV e antigen (HBeAg)-positive
and 101 HBeAg-negative patients with anti-HBV nucleos(t)ide analogue monotherapy
were enrolled with on-treatment follow-ups for at least one year. IgG1 N-glycome
was profiled using mass spectrometry and evaluated for its relevance in treatment
responses. The results indicated that a high level of serum fucosyl-agalactosyl
IgG1 (IgG1-G0F) at baseline was associated with the severity of liver
inflammation and damage but advanced treatment responses, including HBV DNA loss,
HBeAg seroconversion, a reduced drug resistance rate, and a liver histological
improvement at year 1, thereby improving the long-term treatment efficacy and the
probability of treatment discontinuation in HBeAg-positive patients. Stepwise Cox
regression analyses revealed that baseline IgG1-G0F >30% was an independent
factor that links to virological response (HR 3.071, 95% CI 1.835-5.141, P <
0.001) or HBeAg seroconversion (HR 2.034, 95% CI 1.011-4.093, P = 0.046).
Furthermore, a high IgG1-G0F level at the treatment endpoint was associated with
an off-treatment sustained virological response. In conclusion, IgG1-G0F favors
the medication outcome for HBeAg-positive chronic hepatitis B.
PMID- 28512354
TI - Neglect Patients Exhibit Egocentric or Allocentric Neglect for the Same Stimulus
Contingent upon Task Demands.
AB - Hemispatial Neglect (HN) is a failure to allocate attention to a region of space
opposite to where damage has occurred in the brain, usually the left side of
space. It is widely documented that there are two types of neglect: egocentric
neglect (neglect of information falling on the individual's left side) and
allocentric neglect (neglect of the left side of each object, regardless of the
position of that object in relation to the individual). We set out to address
whether neglect presentation could be modified from egocentric to allocentric
through manipulating the task demands whilst keeping the physical stimulus
constant by measuring the eye movement behaviour of a single group of neglect
patients engaged in two different tasks (copying and tracing). Eye movements and
behavioural data demonstrated that patients exhibited symptoms consistent with
egocentric neglect in one task (tracing), and allocentric neglect in another task
(copying), suggesting that task requirements may influence the nature of the
neglect symptoms produced by the same individual. Different task demands may be
able to explain differential neglect symptoms in some individuals.
PMID- 28512356
TI - Adamdec1, Ednrb and Ptgs1/Cox1, inflammation genes upregulated in the intestinal
mucosa of obese rats, are downregulated by three probiotic strains.
AB - We have previously reported that administration of Lactobacillus paracasei CNCM I
4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036
to obese Zucker-Lepr fa/fa rats attenuates liver steatosis and exerts anti
inflammatory effects. The goal of the present work was to investigate the
modulation of gene expression in intestinal mucosa samples of obese Zucker-Lepr
fa/fa rats fed the probiotic strains using a DNA microarray and postgenomic
techniques. We also measured secretory IgA content in the gut and
lipopolysaccharide (LPS)-binding protein (LBP) in serum. Expression of three
genes (Adamdec1, Ednrb and Ptgs1/Cox1) was up-regulated in the intestinal mucosa
of the obese rats compared with that in the rats when they were still lean.
Probiotic administration down-regulated expression of Adamdec1 and Ednrb at the
mRNA and protein levels and that of Ptgs1/Cox1 at the mRNA level, and this effect
was in part mediated by a decrease in both macrophage and dendritic cell
populations. Probiotic treatment also increased secretory IgA content and
diminished the LBP concentration. Based on results reported in this work and else
where, we propose a possible mechanism of action for these bacterial strains.
PMID- 28512355
TI - Ancient and recent admixture layers in Sicily and Southern Italy trace multiple
migration routes along the Mediterranean.
AB - The Mediterranean shores stretching between Sicily, Southern Italy and the
Southern Balkans witnessed a long series of migration processes and cultural
exchanges. Accordingly, present-day population diversity is composed by multiple
genetic layers, which make the deciphering of different ancestral and historical
contributes particularly challenging. We address this issue by genotyping 511
samples from 23 populations of Sicily, Southern Italy, Greece and Albania with
the Illumina GenoChip Array, also including new samples from Albanian- and Greek
speaking ethno-linguistic minorities of Southern Italy. Our results reveal a
shared Mediterranean genetic continuity, extending from Sicily to Cyprus, where
Southern Italian populations appear genetically closer to Greek-speaking islands
than to continental Greece. Besides a predominant Neolithic background, we
identify traces of Post-Neolithic Levantine- and Caucasus-related ancestries,
compatible with maritime Bronze-Age migrations. We argue that these results may
have important implications in the cultural history of Europe, such as in the
diffusion of some Indo-European languages. Instead, recent historical expansions
from North-Eastern Europe account for the observed differentiation of present-day
continental Southern Balkan groups. Patterns of IBD-sharing directly reconnect
Albanian-speaking Arbereshe with a recent Balkan-source origin, while Greek
speaking communities of Southern Italy cluster with their Italian-speaking
neighbours suggesting a long-term history of presence in Southern Italy.
PMID- 28512357
TI - Effect of seed position and soil nutrients on seed mass, germination and seedling
growth in Peucedanum oreoselinum (Apiaceae).
AB - There is large variation in seed mass within P. oreoselinum (L.) Moench selected
for the present study from two contrasting habitats: roadside and oak forest.
Effect of seed position within a plant and of soil nutrients on seed mass,
germination and seedlings growth were studied. Within an individual plant, seed
mass decreased with umbel order and seeds from the central umbellet of the umbel
were lighter than those from the outer edge, suggesting that variation in seed
mass within an individual plant was due to the position effect. There was a
significant relationship between seed mass and total germination. Covariate
analysis showed the differences between sites in seed macronutrient contents were
caused by respective differences in seed mass and soil macronutrients. This
indicates substantial variation in the amount of reserves initially available for
seedling growth. In conclusion, phenotypically-based variation in seed mass may
arise from soil conditions, maternal traits or combination of the two. High
variability in seed mass of P. oreoselinum favours its widespread geographic
distribution. These results suggest that with respect to germination
characteristics large seeds from primary order have a competitive advantage over
small seeds produced on secondary umbels because they have higher overall
germination.
PMID- 28512351
TI - Non-homologous DNA end joining and alternative pathways to double-strand break
repair.
AB - DNA double-strand breaks (DSBs) are the most dangerous type of DNA damage because
they can result in the loss of large chromosomal regions. In all mammalian cells,
DSBs that occur throughout the cell cycle are repaired predominantly by the non
homologous DNA end joining (NHEJ) pathway. Defects in NHEJ result in sensitivity
to ionizing radiation and the ablation of lymphocytes. The NHEJ pathway utilizes
proteins that recognize, resect, polymerize and ligate the DNA ends in a flexible
manner. This flexibility permits NHEJ to function on a wide range of DNA-end
configurations, with the resulting repaired DNA junctions often containing
mutations. In this Review, we discuss the most recent findings regarding the
relative involvement of the different NHEJ proteins in the repair of various DNA
end configurations. We also discuss the shunting of DNA-end repair to the
auxiliary pathways of alternative end joining (a-EJ) or single-strand annealing
(SSA) and the relevance of these different pathways to human disease.
PMID- 28512350
TI - Mechanisms of action and regulation of ATP-dependent chromatin-remodelling
complexes.
AB - Cells utilize diverse ATP-dependent nucleosome-remodelling complexes to carry out
histone sliding, ejection or the incorporation of histone variants, suggesting
that different mechanisms of action are used by the various chromatin-remodelling
complex subfamilies. However, all chromatin-remodelling complex subfamilies
contain an ATPase-translocase 'motor' that translocates DNA from a common
location within the nucleosome. In this Review, we discuss (and illustrate with
animations) an alternative, unifying mechanism of chromatin remodelling, which is
based on the regulation of DNA translocation. We propose the 'hourglass' model of
remodeller function, in which each remodeller subfamily utilizes diverse
specialized proteins and protein domains to assist in nucleosome targeting or to
differentially detect nucleosome epitopes. These modules converge to regulate a
common DNA translocation mechanism, to inform the conserved ATPase 'motor' on
whether and how to apply DNA translocation, which together achieve the various
outcomes of chromatin remodelling: nucleosome assembly, chromatin access and
nucleosome editing.
PMID- 28512359
TI - The perceived stability of scenes: serial dependence in ensemble representations.
AB - We are continuously surrounded by a noisy and ever-changing environment. Instead
of analyzing all the elements in a scene, our visual system has the ability to
compress an enormous amount of visual information into ensemble representations,
such as perceiving a forest instead of every single tree. Still, it is unclear
why such complex scenes appear to be the same from moment to moment despite
fluctuations, noise, and discontinuities in retinal images. The general effects
of change blindness are usually thought to stabilize scene perception, making us
unaware of minor inconsistencies between scenes. Here, we propose an alternative,
that stable scene perception is actively achieved by the visual system through
global serial dependencies: the appearance of scene gist is sequentially
dependent on the gist perceived in previous moments. To test this hypothesis, we
used summary statistical information as a proxy for "gist" level, global
information in a scene. We found evidence for serial dependence in summary
statistical representations. Furthermore, we show that this kind of serial
dependence occurs at the ensemble level, where local elements are already merged
into global representations. Taken together, our results provide a mechanism
through which serial dependence can promote the apparent consistency of scenes
over time.
PMID- 28512358
TI - Delayed epidural transplantation of human induced pluripotent stem cell-derived
neural progenitors enhances functional recovery after stroke.
AB - Induced pluripotent stem cell-derived neural progenitor cells (iPSC-NPCs) are a
promising source of tailor-made cell therapy for neurological diseases. However,
major obstacles to clinical use still exist. To circumvent complications related
to intracerebral administration, we implanted human iPSC-NPCs epidurally over the
peri-infarct cortex 7 days after permanent middle cerebral artery occlusion in
adult rats. Compared to controls, cell-treated rats showed significant
improvements in paretic forelimb usage and grip strength from 10 days post
transplantation (dpt) onwards, as well as reductions in lesion volumes,
inflammatory infiltration and astrogliosis at 21 dpt. Few iPSC-NPCs migrated into
rat peri-infarct cortices and exhibited poor survival in tissue. To examine the
paracrine therapeutic mechanisms of epidural iPSC-NPC grafts, we used
transmembrane co-cultures of human iPSC-NPCs with rat cortical cells subjected to
oxygen-glucose deprivation. Compared to other human stem cells, iPSC-NPCs were
superior at promoting neuronal survival and outgrowth, and mitigating
astrogliosis. Using comparative whole-genome microarrays and cytokine
neutralization, we identified a neurorestorative secretome from iPSC-NPCs, and
neutralizing enriched cytokines abolished neuroprotective effects in co-cultures.
This proof-of-concept study demonstrates a relatively safe, yet effective
epidural route for delivering human iPSC-NPCs, which acts predominately through
discrete paracrine effects to promote functional recovery after stroke.
PMID- 28512360
TI - Bullying behavior and mental health in healthcare and educational sectors in
Kaunas, Lithuania.
AB - BACKGROUND: Investigations on workplace bullying in the countries of Eastern
Europe are yet not too extensive. The aim of the study has been to identify the
most frequent bullying behavior and to explore the associations with
psychological distress and post-traumatic stress symptoms in 3 female-dominated
occupations in Kaunas, Lithuania. MATERIAL AND METHODS: This crosssectional study
employed 517 teachers (response rate (RR) = 71.3%), 174 family physicians (RR =
65.7%) and 311 internal medicine department nurses (RR = 69.1%). The twenty-two
item Negative Acts Questionnaire was used for measuring the exposure to bullying
behavior, Goldberg 12-item General Health Questionnaire (GHQ-12) - psychological
distress, Event Scale-Revised (IES-R) inventory - post-traumatic stress symptoms,
Karasek & Theorell Demand-Control questionnaire - psychosocial job
characteristics. The International Business Machines Corporation (IBM) SPSS
Statistics version 20.0 was used for performing the statistical analysis.
Logistic regression was used for assessing the associations among 22 negative
acts as continuous variable and mental health outcomes adjusting to age,
psychosocial factors at work and everyday life. RESULTS: Exposure to workplace
bullying behavior on a weekly/daily basis was prevalent among family physicians
at the rate of 19%, among nurses - 12.9%, among teachers - 4.1%. Even after
adjustment to age, psychosocial job characteristics and threatening life events,
the exposure to 22 negative acts as continuous variable was significantly
associated with psychological distress and post-traumatic stress symptoms for all
3 occupations. CONCLUSIONS: Health care sector is particularly affected by
workplace bullying. Exposure to bullying behavior was associated with mental
health problems for all 3 occupations. Preventive measures are necessary to
improve psychosocial work environment conditions in healthcare and educational
institutions in Lithuania. Med Pr 2017;68(3):307-314.
PMID- 28512361
TI - Quantification of lower extremity physical exposures in various combinations of
sit/stand time duration associated with sit-stand workstation.
AB - BACKGROUND: Sit-stand workstations are available for office work purposes but
there is a dearth of quantitative evidence to state benefits for lower limb
outcomes while using them. And there are no guidelines on what constitutes
appropriate sit/stand time duration. The primary aim of this study has been to
compare muscle activity and perceived discomfort in the lower extremity during
various combinations of sit/stand time duration associated with a sit-stand
workstation separately and to evaluate the effects of the sit-stand workstation
on the lower extremity during the text entry task. MATERIAL AND METHODS: During
the 5 days, all participants completed a 2-h text entry task each day for various
sit/stand time duration combinations as follows: 5/25 min, 10/20 min, 15/15 min,
20/10 min, 25/5 min. Lower extremity muscular exposure of 12 male and 13 female
participants was collected at 8 sites by surface electromyography and body
discomfort was calculated by a questionnaire under those 5 conditions. RESULTS:
Results have demonstrated that lower extremity muscle activity has been
significantly varied among the 5 sit/stand time duration groups. Perceived level
of discomfort (PLD) has not differed significantly for 9 out of 10 body parts.
CONCLUSIONS: The muscle activity of the thigh region was influenced by sit/stand
time duration significantly. Ergonomic exposures of lower extremity when using a
sit-stand workstation were increased, particularly during the long time standing
posture. Results indicate that body mass index (BMI) and gender were not
significant factors in this study. Combination of sit/stand time duration 25/5
min appears to show positive effects on relief of muscle exposure of back of
thigh in the shifts of sitting and standing work position. Med Pr 2017;68(3):315
327.
PMID- 28512362
TI - [Copenhagen Psychosocial Questionnaire (COPSOQ) - Psychometric properties of
selected scales in the Polish version].
AB - BACKGROUND: The Copenhagen Psychosocial Questionniare (COPSOQ) has many
advantages as compared to other similar instruments, i.a., it is not related to
one single theoretical model and it measures a wide spectrum of psychosocial
working conditions that have shown proven impact on health. The aim of the
article is to summarize information on psychometric properties of 11 scales in
the Polish version: Quantitative Demands, Emotional Demands, Influence at Work,
Social Support, Possibilities for Development, Meaning of Work, Role Clarity,
Quality of Leadership, Job Insecurity, Job Satisfaction, and General Health.
MATERIAL AND METHODS: Analyses were based on the results of 4 research projects,
in which the Polish version of the COPCOQ scales has been used: on a
representative sample of Polish nurses (N = 4354), job insecurity in 2 groups of
civil servants (N = 295, N = 724), mobbing among teachers (N = 1037) and
psychological consequences of restructuring (N = 1396). The following
psychometric characteristics were analysed: internal reliability, theoretical
validity, and factorial validity. RESULTS: Internal reliability of the following
8 scales was found satisfactory: Quantitative Demands, Influence at Work, Social
Support, Possibilities for Development, Meaning of Work, Quality of Leadership,
Job Satisfaction, and General Health (Cronbach's alpha = 0.7-0.91, depending on
the scale). The results of exploratory factor analyses indicated factorial
separateness of the above mentioned scales. Theoretical validity of 11 scales was
confirmed; they were associated with variables that can be regarded as their
validity criteria. CONCLUSIONS: The 8 COPSOQ scales, in the Polish version, can
be recommended for using in the research involving psychosocial job
characteristics. Mean scores on these scales and standard deviations given in the
article can serve as reference points during an evaluation of received results.
Med Pr 2017;68(3):329-348.
PMID- 28512364
TI - [Radiographic implications of procedures involving cardiac implantable electronic
devices (CIEDs) - Selected aspects].
AB - BACKGROUND: Some cardiac implantable electronic device (CIED) implantation
procedures require the use of X-rays, which is reflected by such parameters as
total fluoroscopy time (TFT) and dose-area product (DAP - defined as the absorbed
dose multiplied by the area irradiated). MATERIAL AND METHODS: This retrospective
study evaluated 522 CIED implantation (424 de novo and 98 device upgrade and new
lead placement) procedures in 176 women and 346 men (mean age 75+/-11 years) over
the period 2012-2015. The recorded procedure-related parameters TFT and DAP were
evaluated in the subgroups specified below. The group of 424 de novo procedures
included 203 pacemaker (PM) and 171 implantable cardioverter-defibrillator (ICD)
implantation procedures, separately stratified by single-chamber and dual-chamber
systems. Another subgroup of de novo procedures involved 50 cardiac
resynchronization therapy (CRT) devices. The evaluated parameters in the group of
98 upgrade procedures were compared between 2 subgroups: CRT only and combined PM
and ICD implantation procedures. RESULTS: We observed differences in TFT and DAP
values between procedure types, with PM-related procedures showing the lowest,
ICD - intermediate (with values for single-chamber considerably lower than those
for dual-chamber systems) and CRT implantation procedures - highest X-ray
exposure. Upgrades to CRT were associated with 4 times higher TFT and DAP values
in comparison to those during other upgrade procedures. Cardiac resynchronization
therapy de novo implantation procedures and upgrades to CRT showed similar mean
values of these evaluated parameters. CONCLUSIONS: Total fluoroscopy time and DAP
values correlated progressively with CIED implantation procedure complexity, with
CRT-related procedures showing the highest values of both parameters. Med Pr
2017;68(3):363-374.
PMID- 28512363
TI - [Attenuation of earmuffs used simultaneously with respiratory protective
devices].
AB - BACKGROUND: In the work environment, apart from the noise, employees may be
exposed to other harmful factors. Therefore, they wear hearing protectors and
other personal protective equipment. The aim of the study was to determine
whether simultaneous use of earmuffs and respiratory protective devices affects
the attenuation of earmuffs. MATERIAL AND METHODS: The study was conducted in
laboratory conditions using the subjective REAT (Real Ear Attenuation at
Threshold) and objective MIRE (Microphone in Real Ear) methods. The REAT method
was used to measure sound attenuation of earmuffs, while MIRE was used to
determine changes in attenuation of earmuffs due to the use of other personal
protective equipment. RESULTS: The study showed reduction in attenuation of
earmuffs due to the use of a full face mask up to 20 dB. Using a full face mask
causes that attenuation of earmuffs in the low frequency range is close to zero.
Reduction in attenuation due to the use of half masks for complete with particle
filters (half masks) is 3-15 dB. Simultaneous use of earmuffs and filtering half
masks makes small changes in attenuation not exceeding 3 dB. CONCLUSIONS: The
study showed that full face masks give the greatest reduction in attenuation of
earmuffs. On the other hand, the least reduction is observed in the case of
filtering half masks. There is a significant difference between the reduction in
attenuation of earmuffs worn with half masks for complete with particle filters
because they may be equipped with different kind of the head strap. Med Pr
2017;68(3):349-361.
PMID- 28512365
TI - [Temperament risk factor for mental health disturbances in the judiciary staff].
AB - BACKGROUND: The aim of this paper was to examine how temperament might moderate
the health impact of psychosocial hazards at work and thus to attempt to identify
the temperament risk factor in the judiciary staff. MATERIAL AND METHODS: The
data were collected from 355 court employees, including judges, judicial
assistants, court clerks and service workers from criminal, civil, commercial as
well as from labor and social insurance divisions. The psychosocial work
environment was measured with the Psychosocial Working Conditions Questionnaire
by Cieslak and Widerszal-Bazyl, temperament with Cloninger's Temperament and
Character Inventory adopted by Hornowska and employee health status was screened
with Goldberg's General Health Questionnaire- 28 (GHQ-28) adopted by Makowska and
Merecz. The health impact of job strain with moderating effects of temperament
traits was estimated with logistic regression (forward stepwise selection based
on the likelihood ratio for the model). RESULTS: The analyses confirmed the
moderating role of temperament in the health consequences of work-related stress.
High score in novelty seeking was identified as independent temperament risk
factor for mental health disturbances in judiciary staff facing at least medium
job demands. The job control was a protective factor while relative risk of
negative health outcomes was also elevated due to female gender. CONCLUSIONS:
Temperament may control sensitivity to the environmental exposure to psychosocial
hazards at work and its health consequences. Further research is needed to
explore and understand better the moderating role of temperament in the relation
between job stress (strain) and health in different vocational groups and
workplaces. Med Pr 2017;68(3):375-390.
PMID- 28512366
TI - [Effect of alpha-lipoic acid on free radical processes in serum of rats on high
fat diet].
AB - BACKGROUND: Oils are often fried which reduces their beneficial biological and
nutritional properties, contributing to disturbances in homeostasis. Some
antioxidant substances can improve stability of oils. The aim of the study was to
examine the effect of alpha-lipoic acid (ALA) on the concentration of sulfhydryl
groups, lipid peroxides, malondialdehyde, creatinine and urea in serum of rats
fed high fat diet for 3 months. MATERIAL AND METHODS: Thirty six Wistar rats were
equally divided into 6 groups: the control group on standard breeding diet (SB),
oxidized oil (OU) group on SB with 10% oxidized oil, ALA10 group on SB with ALA
10 mg/kg of body weight (b.w.), OU+ALA10 group on SB with oxidized oil and ALA
(10 mg/kg b.w.), ALA50 group on SB with ALA in a dose of 50 mg/kg b.w., OU+ALA50
group on SB with oxidized oil and ALA (50 mg/kg b.w.). Oil was oxidized in 180
degrees C for 6 h. RESULTS: We observed decrease in concentration of protein
sulfhydryl (PSH) groups in all study groups except for ALA10 vs. control group
(C) and increase in OU+ALA10 and OU+ALA50 vs. OU; increase in the lipid
hydroperoxide (LHP) concentration in OU, OU+ALA10 and OU+ALA50 vs. C and decrease
in all study groups vs. OU; increase of malondialdehyde (MDA) in OU vs. all other
groups. And also increase in creatinine and urea concentration in OU group.
CONCLUSIONS: High fat diet rich in oxidized oil intensifies the lipid
peroxidation process and oxidation of sulfhydryl groups. It can also impair
kidney function. Administration of lipoic acid in a dose of 10 mg/kg b.w.
inhibits the lipid peroxidation and protects sulfhydryl groups. Med Pr
2017;68(3):391-399.
PMID- 28512367
TI - [Theoretical models of drivers behavior on the road].
AB - Understanding of mechanisms and factors responsible for the driver behavior on
the road is the subject of ongoing interest to transportation psychologists,
occupational doctors and engineers. Models of driver behavior are a key point for
the understanding the mechanisms and factors which may cause limitations to the
optimal functioning on the road. They also systematize knowledge about the
factors responsible for the behavior of the driver and thus constitute a starting
point for formulating empirical or diagnostic hypotheses. The aim of this study
is to present models of driver behavior from the descriptive and functional
perspectives. Med Pr 2017;68(3):401-411.
PMID- 28512368
TI - [Analysis of the phenomenon of over-the-counter drug abuse and not controlled
herbs trade by polish adolescents: Part I].
AB - The phenomenon of stupefying by the use of available over-the-counter drugs (OTC)
among adolescents is an essential problem in both Poland and throughout the
world. Popular analgesics, cold medicine and antihistamines contain psychedelic
substances, such as dextromethorphan (DXM), pseudoephedrine/ephedrine, codeine
(methylmorphine), dimenhydrinate, paracetamol (acetaminophren) and others. Cases
of fatal addiction to dextromethorphan, one of the active substances contained in
medicines, e.g., the common cold, have been reported. The test results cited by
the authors clearly indicate that the use of OTC drugs, whose turnover is not
controlled is a domain of females. The extent of use of drugs not prescribed by a
doctor has remained for many years at a constant level. The most common
poisonings with OTC drugs are caused by those that affect the respiratory system
or exert analgesic or antipyretic effects. They are also used in attempted
suicides, especially among females. Analyzing poisonings caused by OTC
medications their seasonality has been observed. Their number increases during
spring-autumn. A territorial differentiation in areas of OTC drug trade in terms
of their quantities, with the predominance of southern regions is also noted.
Intoxication with psychoactive substances causes the deterioration of relations
between young people. In the reviewed studies there is no detailed information on
the composition of non-prescription medicines. Moreover, young people have easy
access to mushroom fungi, growing in nearby forests and meadows that may have
hallucinogenic effects and are available in pharmacies and on the Internet. Med
Pr 2017;68(3):413-422.
PMID- 28512369
TI - [Nanopesticides - Light or dark side of the force?]
AB - Nanotechnology has been used in many branches of industry, including agriculture,
where nanomaterials are used as carriers of chemical plant protection compounds,
as well as active ingredients. Meanwhile, the effects of nanopesticides exposure
on the human body are unknown. Due to their occupation, farmers should be
particularly monitored. This paper summarizes the use of nanoparticles in
agriculture, the route of potential exposure for agricultural workers and the
current state of knowledge of nanopesticides toxicity to mammalian cells. The
authors also discuss techniques for detecting nanoparticles in the workplace, as
well as biomarkers and effects of exposure. The results of this review indicate
that the use of nanotechnology in agriculture can bring measurable benefits by
reducing the amount of chemicals used for plant protection. However, there is no
research available to determine whether or not the use of pesticide
nanoformulations increases the harmful effects of pesticides. Moreover, the
results of research on cell lines and in animal models suggest that nanoparticles
used as active substance are toxic to mammalian cells. Interestingly, there is
also a complete lack of epidemiological studies on this subject. In the nearest
future the effects of exposure to nanopesticides may require a particular
attention paid by scientists and medical doctors who, treat agricultural workers
and their families. Med Pr 2017;68(3):423-432.
PMID- 28512370
TI - Occupational contact allergy to omeprazole and ranitidine.
AB - Omeprazole is a proton pump inhibition and ranitidine is an H2 histamine receptor
antagonist widely used in the treatment of gastroesophageal reflex disease,
peptic ulcer disease, Zollinger-Ellison syndrome and as a protector of the
gastric mucosae. We report a case of occupational contact allergy to omeprazole
and ranitidine. A 48-year-old man, with no pre-existing history of atopy or
lifestyle factors. He neither had any medical history of consumption of drugs
such as ranitidine and omeprazole. He worked for 19 months in the pharmaceutical
company that manufactured ranitidine base. He presented rash in the face and
eczema on the dorsum of the hands with itching. The study by prick tests with
ranitidine gave negative response. Patch testing with ranitidine base and
ranitidine hydrochloride gave positive response. A month later, when the patient
was asymptomatic he returned to the pharmaceutical company, being switched from
this previous job to the reactor manufacturing omeprazole. A few days after that,
he presented erythematous eruptions involving face and neck with itching. Prick
tests, path tests and in vitro laboratories studies with omeprazole gave
positives. In this case the patient presented hypersensitivity type I at
omeprazole and hypersensitivity type IV at omeprazole and ranitidine. Our
aportation indicates the importance of careful analysis of the occupational
exposure histories of patients with the suspected type I or type IV
hypersensitivity to allergens, to determine whether work exposure is the cause.
Med Pr 2017;68(3):433-435.
PMID- 28512371
TI - First Report of the Spiral Nematode Helicotylenchus microlobus Infecting Soybean
in North Dakota.
AB - Spiral nematodes (Helicotylenchus spp.) are common plant-parasitic nematodes in
fields of many crops. In June 2015, two soil samples were collected from a
soybean field in Richland County, ND. Nematodes were extracted from soil using
the sugar centrifugal flotation method (Jenkins, 1964). Plant-parasitic nematodes
were identified to genus based on morphological features and counted. Both
samples contained spiral nematodes from 1,500 to 3,300 per kilogram of soil. In
June and August 2016, 10 soil samples were collected from the same field.
Nematodes were extracted, and nine of the samples had spiral nematodes ranging
from 125 to 3,065 per kilogram of soil. One soil sample with 1,500 spiral
nematodes per kilogram was used to inoculate two soybean cultivars Sheyenne and
Barnes each in four replicates. After 15 wk of growth at 22 degrees C in a
greenhouse room, the population of spiral nematodes was found to have increased
greatly. The final density was 9,300 +/- 1,701 spiral nematodes per kilogram of
soil for Sheyenne and 9,451 +/- 2,751 for Barnes. The reproductive factor in
Sheyenne and Barnes was 6.2 and 6.3, respectively, indicating that this spiral
nematode infects and reproduces well on these two soybean cultivars. Infected
soybean roots had small brown lesions on the surface. Individual spiral nematodes
were handpicked and examined morphologically and molecularly for species
identification. Morphological measurements of adult females (n = 15) included
body length (mean = 708.5 MUm, range = 600.0-812.0 MUm), stylet (27.6, 26.0
29.0), body width (28.3, 25.0-33.0), lip region end to posterior end of
pharyngeal glands (142.5, 130.0-152.0), anal body width (15.8, 14.0-17.5), tail
length (20.3, 15.0-25.0), tail annules (11.6, 10.0-14.0), a (25.0, 21.4-27.1), b
(5.0, 4.4-5.7), c (35.4, 30.2-41.7), c' (1.3, 1.0-1.6), and V (61.8%, 60.0-63.7).
The spiral nematode was identified as Helicotylenchus microlobus according to
morphological and morphometric characteristics (Subbotin et al., 2015). DNA was
extracted from single nematodes (n = 8) using the Proteinase K method (Kumari and
Subbotin, 2012). The internal transcribed spacer (ITS) region of rDNA was
amplified with the primers rDNA2/rDNA1.58S (Cherry et al., 1997). The PCR
products were then purified and sequenced. The consensus ITS rDNA sequence
(accession no. KY271078, 822 bp) that was deposited into the GenBank shared 99%
identity with two isolates of H. microlobus from California (KM506860.1 and
KM506859.1) and one isolate of H. microlobus from Spain (KM506862.1) (Subbotin et
al., 2015). It had only 91% sequence identity with seven isolates of H.
pseudorobustus (KM506875.1, KM506880.1, KM506876.1, KM506874.1, KM506872.1,
KM506879.1, and KM506878.1) from California, Switzerland, and New Zealand, a
spiral nematode species very closely related to H. microlobus in morphology. The
molecular tests confirmed the identity of this spiral nematode as H. microlobus.
The H. microlobus nematode was reported as one of the most commonly observed
spiral nematodes in soil samples in the state of Minnesota, and all 13 soybean
cultivars tested except Hawkeye were rated as hosts (Taylor, 1960). To our
knowledge, this is the first report of H. microlobus in North Dakota.
PMID- 28512372
TI - Characterization of Lilium longiflorum cv. 'Nellie White' Infection with Root
lesion Nematode Pratylenchus penetrans by Bright-field and Transmission Electron
Microscopy.
AB - Lilium longiflorum cv. Nellie White, commonly known as Easter lily, is an
important floral crop with an annual wholesale value of over $26 million in the
United States. The root-lesion nematode, Pratylenchus penetrans, is a major pest
of lily due to the significant root damage it causes. In this study, we
investigated the cytological aspects of this plant-nematode interaction using
bright-field and transmission electron microscopy. We took advantage of an in
vitro culture method to multiply lilies and follow the nematode infection over
time. Phenotypic reactions of roots inoculated with P. penetrans were evaluated
from 0 to 60 d after nematode infection. Symptom development progressed from
initial randomly distributed discrete necrotic areas to advanced necrosis along
entire roots of each inoculated plant. A major feature characterizing this
susceptible host response to nematode infection was the formation of necrosis,
browning, and tissue death involving both root epidermis and cortical cells.
Degradation of consecutive cell walls resulted in loss of cell pressure, lack of
cytoplasmic integrity, followed by cell death along the intracellular path of the
nematode's migration. Pratylenchus penetrans was never seen in the vascular
cylinder as the layer of collapsed endodermal cells presumably blocked the
progression of nematodes into this area of the roots. This study presents the
first detailed cytological characterization of P. penetrans infection of Easter
lily plants.
PMID- 28512373
TI - Assessment of Globodera pallida RNA Extracted from Solanum Roots.
AB - The introduction of high-throughput sequencing technologies has made
transcriptome analyses of plant-pathogen interactions almost routine.
Nevertheless, it is still challenging to obtain RNA from populations made up of
two species. An RNA extraction method that worked well on free-living
Caenorhabditis elegans failed when applied to isolated Globodera pallida J2
larva. Furthermore, alternative protocols that extracted RNA from free-living J2
larva produced less satisfactory results once the animals entered their hosts'
roots. We have compared several extraction procedures to ascertain whether a
single protocol was capable of recovering high-quality, high-molecular-weight RNA
from newly hatched J2 larva as well as from larva embedded in roots of both
potatoes (Solanum tuberosum L. cv. Desiree) and a very distantly related species,
Solanum sisymbriifolium. Although it was possible to recover large amounts of RNA
from J2 larvae using Proteinase K treatments, this protocol failed to yield high
quality nematode RNA from infected roots. By comparison, mechanical disruption
procedures yielded lower amounts of RNA from infected roots, but what was
recovered was of higher quality. We conclude that different extraction protocols
need to be developed to sample mixed populations of organisms.
PMID- 28512374
TI - Description of Enchodorus yeatsi n. sp. (Dorylaimida, Nordiidae) from Southern
Iran and Its Molecular Phylogenetic Study.
AB - Enchodorus yeatsi n. sp., a new species of the rare genus Enchodorus is described
and illustrated based on its morphological and molecular characters. It was
recovered from southern Iran. Females of the new species are characterized by
having 1,511.3- to 1,792.5-um long slender body, angular lip region having
prominent papillae, 12- to 13-um long odontostyle, double guiding ring, simple
rod-like odontophore, didelphic-amphidelphic reproductive system, and 102- to 160
um long elongate-conoid tail with rounded tip. Males of the new species are
abundant and functional, characterized by 1,484- to 1,576-um long body, 40- to 43
um long spicules, 5 to 6 ventromedian supplements, and ventrally bent elongate
conical tail. Compared to the type species, Enchodorus dolichurus, the new
species has differences in its tail morphology and V value. These morphological
differences and the separation of two species was further supported with basic
differences in sequences of 28S rDNA D2/D3 and internal transcribed spacer 1
(ITS1) fragments. Compared to Enchodorus neodolichurus, it has basic differences
in tail characters and spicule lengths. Molecular phylogenetic studies using
partial sequences of 28S rDNA D2/D3 fragment of the new species and available
sequences of Nordiidae members and several other dorylaim species/genera,
revealed E. yeatsi n. sp. and E. dolichurus forming a clade with 0.81 Bayesian
posterior probability (BPP). This clade forms a sister clade to the clade of
Heterodorus sp. and Rhyssocolpus vinciguerrae, again with 0.81 BPP. In ITS1 tree,
reconstructed using few available sequences, the new species and E. dolichurus
formed a clade with 0.98 BPP.
PMID- 28512375
TI - A Simple Express Technique to Process Nematodes for Collection Slide Mounts.
AB - The new simple technique of hot fixation and a method for processing a mass
quantity of nematodes to prepare nematode collection slides for taxonomic and
ecological purposes, combined with an abrupt reduction of the set of procedures
caused by the "cocktail" principle (a stratification of layers with a gradient of
glycerol concentrations), are described.
PMID- 28512376
TI - Oscheius microvilli n. sp. (Nematoda: Rhabditidae): A Facultatively Pathogenic
Nematode from Chongming Island, China.
AB - A new species, Oscheius microvilli n. sp., was found on Chongming Island
(Shanghai, China). The new species is morphologically similar to the type strain
of Oscheius myriophilus, but can be distinguished from it and other species of
Oscheius on the basis of unique morphological characteristics of the bursa as
well as male papillae. In this new species, the male bursal papillar formula is
2, 1, 3, 3 with everted tips in the first, fifth, and seventh pairs. The bursal
rim is jagged, joins together anterior to the spicules, and is partially extended
and decorated with microvilli. The spicules are incompletely separated, and the
tail does not extend beyond the bursa. Phylogenetic trees of 18S rDNA and
internal transcribed spacer indicate that the new species belongs to the
insectivora group of the genus Oscheius; it is most closely related to O.
myriophilus, and the two species can be distinguished on the basis of their
different body length, morphological features of the bursa, and molecular data.
The new species is facultatively associated with a bacterial strain of Serratia.
The LC50 of this novel nematode against Galleria mellonella was 69.1 dauer
juveniles per milliliter after 48 hr of infection.
PMID- 28512377
TI - Species Delimitation and Description of Mesocriconema nebraskense n. sp.
(Nematoda: Criconematidae), a Morphologically Cryptic, Parthenogenetic Species
from North American Grasslands.
AB - Nematode surveys of North American grasslands conducted from 2010 to 2015
frequently recovered a species of criconematid nematode morphologically
resembling Mesocriconema curvatum. These specimens were recovered from remnant
native prairies in the central tallgrass ecoregion of North America, and not from
surrounding agroecosystems. Historical records indicate that M. curvatum is a
cosmopolitan species feeding on a wide range of agronomic and native plants. DNA
barcoding indicates North American grasslands contain at least 10
phylogenetically distinct lineages of Mesocriconema that resemble, but are not,
M. curvatum. Analysis of the two most common lineages reveals two distinctly
different population structures. The variation in population structure suggests
unique evolutionary histories associated with their diversification. These two
major lineages share a sympatric distribution and their slight morphological
differences contrast with a high level of genetic separation. Based on their
genetic divergence, fixed diagnostic nucleotides, population structure, species
delimitation metrics, and a sympatric distribution, we believe that one of these
distinct lineages warrants formal nomenclatural recognition. Herein, we provide
formal recognition for Mesocriconema nebraskense n. sp. and discuss its
relationship to other Mesocriconema lineages discovered in native North American
grasslands.
PMID- 28512378
TI - Description of Aphelenchoides macrospica n. sp. (Nematoda: Aphelenchoididae) from
Northwestern Iran.
AB - Aphelenchoides macrospica n. sp. is described and illustrated from the West
Azerbayjan province, northwestern Iran. The new species is characterized by its
body length of 807 to 963 MUm (males) and 792 to 1,094 MUm (females), offset
cephalic region, lateral fields with four incisures, long stylet with 15 to 16
MUm length, and excretory pore situated opposite or behind the nerve ring.
Pharyngeal glands overlapping intestine dorsally and extending for 90 to 121 MUm,
tail terminus mucronate in both sexes. Vagina directed anteriad, and spicules are
relatively large (27-32 MUm) with well-developed broadly rounded apex and
condylus. The new species comes close to seven known species of the genus namely
A. arcticus, A. blastophthorus, A. haguei, A. huntensis, A. lucknowensis, A.
parasaprophilus, and A. xui, but it differs from them by the body size, stylet
length, size of spicules, and length of postvulval uterine sac. The results of
phylogenetic analyses based on sequences of D2-D3 expansion region of 28S and 18S
rDNA, confirmed its status as a new species.
PMID- 28512379
TI - Evaluation of Pochonia chlamydosporia and Purpureocillium lilacinum for
Suppression of Meloidogyne enterolobii on Tomato and Banana.
AB - Meloidogyne enterolobii is one of the most important root-knot nematode in
tropical regions, due to its ability to overcome resistance mechanisms of a
number of host plants. The lack of new and safe active ingredients against this
nematode has restricted control alternatives for growers. Egg-parasitic fungi
have been considered as potential candidates for the development of
bionematicides. In tissue culture plates, Pochonia chlamydosporia (var.
catenulata and chlamydosporia) and Purpureocillium lilacinum strains were
screened for their ability to infect eggs of the root-knot nematode M.
enterolobii on water-agar surfaces. Reduction in the hatching of J2 varied from
13% to 84%, depending on strain. The more efficacious strains reduced
hatchability of J2 by 57% to 84% when compared to untreated eggs, but average
reductions were only 37% to 55% when the same strains were applied to egg masses.
Combinations of fungal isolates (one of each species) did not increase the
control efficacy in vitro. In experiments in which 10,000 nematode eggs were
inoculated per plant, reductions in the number of eggs after 12 months were seen
in three of four treatments in banana plants, reaching 34% for P. chlamydosporia
var. catenulata. No significant reductions were seen in tomato plants after 3
mon. In another experiment with tomato plants using either P. chlamydosporia var.
catenulata or P. lilacinum, the number of eggs was reduced by 34% and 44%,
respectively, when initial infestation level was low (500 nematode eggs per
plant), but tested strains were not effective under a moderate infestation level
(5,000 eggs per plant). Under all infestation levels tested in this work, gall
and egg mass indexes (MI) did not differ from the untreated controls, bringing
concerns related to the practical adoption of this control strategy by farmers.
In our opinion, if the fungi P. chlamydosporia and P. lilacinum are to be used as
biocontrol tools toward M. entorolobii, they should focus on agricultural
settings with low soil infestation levels and within an IPM approach.
PMID- 28512380
TI - Esteya vermicola Controls the Pinewood Nematode, Bursaphelenchus xylophilus, in
Pine Seedlings.
AB - Esteya vermicola (Ophiostomataceae) is an endoparasitic fungus that has great
potential as a biological control agent against the pinewood nematode
Bursaphelenchus xylophilus which causes pine wilt disease. We tested E. vermicola
for control of pine wilt disease by spraying E. vermicola conidia on artificial
wounds on pine seedlings, and the optimum E. vermicola treatment density and
application time were also investigated in the greenhouse. The wounds were
similar to those made by sawyer beetles (Coleoptera: Cerambycidae). Esteya
vermicola treatments significantly increased the survival rate of pine seedlings
that were infected by pinewood nematodes. Wounded plants sprayed with 107 CFU/ml
E. vermicola had a 73.0% greater survival rate than nonwounded pine seedlings
treated similarly. The treatment of pine seedlings with 107 CFU/ml E. vermicola
14 d before nematode infection increased their survival rate by 90.0%. The number
of pinewood nematodes isolated from dead pine seedlings sprayed with E. vermicola
was 76% less than the number of pinewood nematodes in the controls. Moreover,
infected nematodes and the hyphae of E. vermicola were detected in the dead or
wilting pine seedlings. Therefore, spraying E. vermicola on the wounds of pine
seedlings made by sawyer beetles provides good control of the pine wilt disease
that is caused by pinewood nematodes.
PMID- 28512381
TI - First Report and Comparative Study of Steinernema surkhetense (Rhabditida:
Steinernematidae) and its Symbiont Bacteria from Subcontinental India.
AB - Two populations (CS19 and CS20) of entomopathogenic nematodes were isolated from
the soils of vegetable fields from Bijnor district, India. Based on
morphological, morphometrical, and molecular studies, the nematodes were
identified as Steinernema surkhetense. This work represents the first report of
this species in India. The infective juveniles (IJs) showed morphometrical and
morphological differences, with the original description based on longer IJs
size. The IJs of the Indian isolates possess six ridges in their lateral field
instead of eight reported in the original description. The analysis of ITS-rDNA
sequences revealed nucleotide differences at 345, 608, and 920 positions in
aligned data. No difference was observed in D2-D3 domain. The S. surkhetense COI
gene was studied for the first time as well as the molecular characterization of
their Xenorhabdus symbiont using the sequences of recA and gyrB genes revealing
Xenorhabdus stockiae as its symbiont. These data, together with the finding of X.
stockiae, suggest that this bacterium is widespread among South Asian nematodes
from the "carpocapsae" group. Virulence of both isolates was tested on Spodoptera
litura. The strain CS19 was capable to kill the larvae with 31.78 IJs at 72 hr,
whereas CS20 needed 67.7 IJs.
PMID- 28512382
TI - Occurrence of Belonolaimus in Sinaloa, Northwestern Mexico: A New Report on
Distribution and Host Range.
AB - The present study reports the occurrence of the genus Belonolaimus in the state
of Sinaloa, Mexico, associated with native plants (i.e., Ziziphus amole and
Stenocereus alamosensis) in a natural coastal ecosystem. Both morphological and
molecular approaches were employed to characterize the Sinaloa population.
Notwithstanding of some morphological and morphometric variation between
Belonolaimus from Sinaloa and other valid species, the characterization indicates
that this population might belong to the Belonolaimus longicaudatus species
complex. Molecular analyses based on the 28S gene and ITS1-5.8S-ITS2 regions of
the ribosomal RNA (rRNA) identified four major clades within Belonolaimus;
however, none of the species including B. longicaudatus, B. gracilis, and B.
euthychilus were supported as monophyletic; yet monophyly is argued to be a basic
requirement of species status. Sequence divergence among different Belonolaimus
populations and species varied according to the rRNA dataset (i.e., ITS1-5.8S
ITS2 > 28S > 18S) used, thus showing the importance of using genes with different
rates of evolution to estimate species relationships. The fact that Belonolaimus
has not been found in other cultivated (including on suitable hosts) areas in
Sinaloa and that this population is relatively distant from the common B.
longicaudatus groups (i.e., clades A and B) suggests that its appearance was not
due to a recent introduction associated with the local agriculture.
PMID- 28512384
TI - Erratum.
AB - [This corrects the article on p. 280 in vol. 48, PMID: 28154434.].
PMID- 28512383
TI - Effects of Cover Crops on Pratylenchus penetrans and the Nematode Community in
Carrot Production.
AB - Cover cropping is a common practice in U.S. Midwest carrot production for soil
conservation, and may affect soil ecology and plant-parasitic nematodes-to which
carrots are very susceptible. This study assessed the impact of cover crops-oats
(Avena sativa), radish (Raphanus sativus) cv. Defender, rape (Brassica napus) cv.
Dwarf Essex, and a mixture of oats and radish-on plant-parasitic nematodes and
soil ecology based on the nematode community in Michigan carrot production
systems. Research was conducted at two field sites where cover crops were grown
in Fall 2014 preceding Summer 2015 carrot production. At Site 1, root-lesion
(Pratylenchus penetrans) and stunt (Tylenchorhynchus sp.) nematodes were present
at low population densities (less than 25 nematodes/100 cm3 soil), but were not
significantly affected (P > 0.05) by cover crops. At Site 2, P. penetrans
population densities were increased (P <= 0.05) by 'Defender' radish compared to
other cover crops or fallow control during cover crop growth and midseason carrot
production. At both sites, there were few short-term impacts of cover cropping on
soil ecology based on the nematode community. At Site 1, only at carrot harvest,
radish-oats mixture and 'Dwarf Essex' rape alone enriched the soil food web based
on the enrichment index (P <= 0.05) while rape and radish increased structure
index values. At Site 2, bacterivore abundance was increased by oats or radish
cover crops compared to control, but only during carrot production. In general,
cover crops did not affect the nematode community until nearly a year after cover
crop growth suggesting that changes in the soil community following cover
cropping may be gradual.
PMID- 28512385
TI - Association of PECAM-1 Gene Polymorphisms with Kawasaki Disease in Chinese
Children.
AB - Kawasaki disease (KD) is an acute systemic vasculitis complicated by development
of coronary artery lesions. PECAM-1 is a kind of cell adhesion molecule, which
plays an important role in coronary artery disease. The relationship between
PECAM-1 gene polymorphisms and their susceptibility to Kawasaki diseases (KD) is
still unclear. In our study, we examined the PECAM-1 gene polymorphisms in 44 KD
patients and 59 healthy children and revealed the correlation of PECAM-1 gene
polymorphisms in KD children with and without coronary artery lesions (CAL).
PMID- 28512386
TI - Oxidative Stress Biomarkers: Establishment of Reference Values for Isoprostanes,
AOPP, and NPBI in Cord Blood.
AB - Oxidative stress (OS) is a common pathogenic factor involved in the onset of
several diseases in humans, from immunologic disorders to malignancy, being a
serious public health problem. In perinatal period, OS has been associated with
adverse outcome of pregnancy and neonatal diseases. Dangerous effects of OS are
mediated by increased production of free radicals (FRs) following various
mechanisms, such as hypoxia, ischemia reperfusion, hyperoxia, inflammation,
mitochondrial dysfunction, Fenton chemistry, and prostaglandin metabolism. FRs
have short half-life, and their measurement in vivo is faced with many
challenges. However, oxyradical derivatives are stable and thus may be measured
and monitored repeatedly. The quantification of OS is based on the measurement of
specific biomarkers in biologic fluids and tissues, which reflect induced
oxidative damage to lipids, proteins, and DNA. Prostanoids, non-protein-bound
iron (NPBI), and advanced oxidation protein products (AOPP) are actually
considered truly specific and reliable for neonatal injury. Defining reference
values for these biomarkers is necessary to investigate their role in neonatal
diseases or also to evaluate the success of treatments. In this work, we wanted
to define laboratory reference values for biomarkers of OS in a healthy
population of term newborns.
PMID- 28512389
TI - Evaluation of Quality of Life at Progression in Patients with Soft Tissue
Sarcoma.
AB - Introduction. Soft Tissue Sarcoma (STS) is a rare malignancy of mesodermal
tissue, with international incidence estimates between 1.8 and 5 per 100,000 per
year. Understanding quality of life (QoL) and the detrimental impact of disease
progression is critical for long-term care and survival. Objectives. The primary
objective was to explore the relationship between disease progression and health
related quality of life (HRQoL) using data from Eisai's study (E7389-G000-309).
Methods. This was a 1 : 1 randomized, open-label, multicenter, Phase 3 study
comparing the efficacy and safety of eribulin versus dacarbazine in patients with
advanced STS. The QoL analysis was conducted for the baseline and progression
populations using the European Organization for Research and Treatment of Cancer
30-item core QoL questionnaire (EORTC QLQ-C30). Results. There were no
statistical differences between the two treatment arms at baseline for any domain
(p > 0.05; n = 452). Of the 399 patients who experienced disease progression
(unadjusted and adjusting for histology), dacarbazine patients had significantly
lower Global Health Status, Physical Functioning scores, and significantly worse
Nausea and Vomiting, Insomnia, and Appetite Loss (p < 0.05). Conclusions. These
results indicate differences in HRQoL overall and at progression between
dacarbazine and eribulin patients, with increases in symptom severity observed
among dacarbazine patients.
PMID- 28512388
TI - Insufficient Humidification of Respiratory Gases in Patients Who Are Undergoing
Therapeutic Hypothermia at a Paediatric and Adult Intensive Care Unit.
AB - For cooled newborn infants, humidifier settings for normothermic condition
provide excessive gas humidity because absolute humidity at saturation is
temperature-dependent. To assess humidification of respiratory gases in patients
who underwent moderate therapeutic hypothermia at a paediatric/adult intensive
care unit, 6 patients were studied over 9 times. Three humidifier settings, 37
default (chamber-outlet, 37 degrees C; Y-piece, 40 degrees C), 33.5-theoretical
(chamber-outlet, 33.5 degrees C; Y-piece, 36.5 degrees C), and 33.5-adjusted
(optimised setting to achieve saturated vapour at 33.5 degrees C using feedback
from a thermohygrometer), were tested. Y-piece gas temperature/humidity and the
incidence of high (>40.6 mg/L) and low (<32.9 mg/L) humidity relative to the
target level (36.6 mg/L) were assessed. Y-piece gas humidity was 32.0 (26.8
37.3), 22.7 (16.9-28.6), and 36.9 (35.5-38.3) mg/L {mean (95% confidence
interval)} for 37-default setting, 33.5-theoretical setting, and 33.5-adjusted
setting, respectively. High humidity was observed in 1 patient with 37-default
setting, whereas low humidity was seen in 5 patients with 37-default setting and
8 patients with 33.5-theoretical setting. With 33.5-adjusted setting, inadequate
Y-piece humidity was not observed. Potential risks of the default humidifier
setting for insufficient respiratory gas humidification were highlighted in
patients cooled at a paediatric/adult intensive care unit. Y-piece gas conditions
can be controlled to the theoretically optimal level by adjusting the setting
guided by Y-piece gas temperature/humidity.
PMID- 28512387
TI - Oncolytic Virus-Based Immunotherapies for Hepatocellular Carcinoma.
AB - Hepatocellular carcinoma is highly refractory cancer which is resistant to
conventional chemotherapy and radiotherapy, carrying a dismal prognosis. Although
many anticancer drugs have been developed for treating HCC, sorafenib is the only
effective treatment, but it only prolongs survival duration for about 3 months.
Recently, oncolytic virotherapy has shown promising results in treating HCCs and
the effects can be more enhanced by adopting immune modulatory molecules. This
review discusses the current status of treating HCC and the effective strategy of
oncolytic virus-based immunotherapy for the treatment of HCCs.
PMID- 28512390
TI - Cystic Lymphangioma of the Colon: Endoscopic Removal beyond the Frontiers of
Size.
AB - Cystic lymphangiomas are benign colonic neoplasms arising from the submucosa.
Traditionally, endoscopic resection has been described for smaller lesions, while
surgery is reserved for larger symptomatic lesions. We present a case of a 69
year-old asymptomatic individual noted to have a cystic lymphangioma of the colon
measuring 5 cm, which was successfully removed with endoloop endoscopic resection
without any complications.
PMID- 28512392
TI - Utility of Glissonean Pedicle Transection for Surgical Treatment of Severe Liver
Trauma.
AB - The most common initial strategy for treatment of severe liver trauma is damage
control in which hemostasis is achieved by perihepatic gauze packing and/or
vascular embolization. However, we encounter patients in whom this strategy alone
is not adequate. We have applied the principles of Glissonean pedicle
transection, a technique that was originally devised to ensure safe and quick
performance of planned hepatectomy for liver cancer, to 3 cases of severe liver
trauma. We performed Glissonean pedicle ligation during damage control surgery in
2 patients and Glissonean pedicle transection during the definitive surgery in 1
patient. We describe the approaches and our experience with them, including
operation times and outcomes. From our experience thus far, it seems that 8-12 h
after the damage control procedure is appropriate for performing the definitive
surgery. Although there are some problems posed by this strategy and cases to
which it will not be applicable, the method seems to be particularly useful for
cases of severe liver trauma in which the damage is extensive and involves the
Glissonean pedicles near the hepatic hilus. We describe our 3 cases in detail and
review our experience in light of the available literature.
PMID- 28512393
TI - Immunoglobulin A Lambda Multiple Myeloma in a Patient with HIV: An Unusual Cause
of Massive Ascites.
AB - Multiple myeloma (MM) is a neoplastic proliferation of plasma cells with
overproduction of monoclonal immunoglobulins and infiltration into the bone and
other organs. Ascites can develop in patients with lymphoproliferative and solid
malignancies involving the peritoneum. However, ascites is unusual in MM and
rarely the initial presenting sign or symptom. The development of ascites can be
due to peritoneal infiltration or secondary to hepatic involvement, heart
failure, or kidney failure. Ascites in MM reflects a more aggressive stage, and
the reported prognosis is poor, with a median survival of 1-2 months. Here we
present a rare case of immunoglobulin A lambda MM presenting with massive
myelomatous ascites.
PMID- 28512391
TI - A Foreign Body (Toothbrush) in the Esophagus of a Patient with Hiatal Hernia.
AB - Toothbrush ingestion is rare and most commonly seen in patients with psychiatric
comorbidities and in young women with a medical history of eating disorders who
try to induce emesis. Long ingested objects, such as a toothbrush, cannot pass
the gastrointestinal tract spontaneously and require endoscopic removal or even a
surgical approach in cases of unsuccessful endoscopic removal or complication
development. We present a case of a 71-year-old male with hiatal hernia without
psychiatric or neurological comorbidity who accidentally ingested a toothbrush
during oral hygiene routine. After X-ray confirmation, the toothbrush was removed
endoscopically.
PMID- 28512394
TI - Successful Endoscopic Management of Late Biliary Cast Syndrome in a Liver
Transplant Recipient: A Case Report.
AB - Biliary cast syndrome (BCS) is an unusual complication of liver transplantation
(LT). The pathophysiology is not known, and it is thought to develop because of
mucosal damage in the bile duct related to obstruction, ischemia, or bacterial
infection. It occurs in 2.5-18% of LT patients and is associated with increased
graft failure, need for retransplantation, and mortality. Here we report on a
case of BCS of late appearance after LT who was successfully treated by
endoscopic means.
PMID- 28512396
TI - A Generic Transferable EEG Decoder for Online Detection of Error Potential in
Target Selection.
AB - Reliable detection of error from electroencephalography (EEG) signals as feedback
while performing a discrete target selection task across sessions and subjects
has a huge scope in real-time rehabilitative application of Brain-computer
Interfacing (BCI). Error Related Potentials (ErrP) are EEG signals which occur
when the participant observes an erroneous feedback from the system. ErrP holds
significance in such closed-loop system, as BCI is prone to error and we need an
effective method of systematic error detection as feedback for correction. In
this paper, we have proposed a novel scheme for online detection of error
feedback directly from the EEG signal in a transferable environment (i.e., across
sessions and across subjects). For this purpose, we have used a P300-speller
dataset available on a BCI competition website. The task involves the subject to
select a letter of a word which is followed by a feedback period. The feedback
period displays the letter selected and, if the selection is wrong, the subject
perceives it by the generation of ErrP signal. Our proposed system is designed to
detect ErrP present in the EEG from new independent datasets, not involved in its
training. Thus, the decoder is trained using EEG features of 16 subjects for
single-trial classification and tested on 10 independent subjects. The decoder
designed for this task is an ensemble of linear discriminant analysis, quadratic
discriminant analysis, and logistic regression classifier. The performance of the
decoder is evaluated using accuracy, F1-score, and Area Under the Curve metric
and the results obtained is 73.97, 83.53, and 73.18%, respectively.
PMID- 28512395
TI - Keypress-Based Musical Preference Is Both Individual and Lawful.
AB - Musical preference is highly individualized and is an area of active study to
develop methods for its quantification. Recently, preference-based behavior,
associated with activity in brain reward circuitry, has been shown to follow
lawful, quantifiable patterns, despite broad variation across individuals. These
patterns, observed using a keypress paradigm with visual stimuli, form the basis
for relative preference theory (RPT). Here, we sought to determine if such
patterns extend to non-visual domains (i.e., audition) and dynamic stimuli,
potentially providing a method to supplement psychometric, physiological, and
neuroimaging approaches to preference quantification. For this study, we adapted
our keypress paradigm to two sets of stimuli consisting of seventeenth to twenty
first century western art music (Classical) and twentieth to twenty-first century
jazz and popular music (Popular). We studied a pilot sample and then a separate
primary experimental sample with this paradigm, and used iterative mathematical
modeling to determine if RPT relationships were observed with high R2 fits. We
further assessed the extent of heterogeneity in the rank ordering of keypress
based responses across subjects. As expected, individual rank orderings of
preferences were quite heterogeneous, yet we observed mathematical patterns
fitting these data similar to those observed previously with visual stimuli.
These patterns in music preference were recurrent across two cohorts and two
stimulus sets, and scaled between individual and group data, adhering to the
requirements for lawfulness. Our findings suggest a general neuroscience
framework that predicts human approach/avoidance behavior, while also allowing
for individual differences and the broad diversity of human choices; the
resulting framework may offer novel approaches to advancing music neuroscience,
or its applications to medicine and recommendation systems.
PMID- 28512397
TI - Leukocyte Expression of Type 1 and Type 2 Purinergic Receptors and Pro
Inflammatory Cytokines during Total Sleep Deprivation and/or Sleep Extension in
Healthy Subjects.
AB - The purinergic type P1 (adenosine A1 and A2A) receptors and the type P2 (X7)
receptor have been suggested to mediate physiological effects of adenosine and
adenosine triphosphate on sleep. We aimed to determine gene expression of A1R
(receptor), A2AR, and P2RX7 in leukocytes of healthy subjects during total sleep
deprivation followed by sleep recovery. Expression of the pro-inflammatory
cytokines IL-1beta and TNF-alpha were also determined as they have been
characterized as sleep regulatory substances, via P2RX7 activation. Blood
sampling was performed on 14 young men (aged 31.9 +/- 3.9) at baseline (B), after
24 h of sleep deprivation (24 h-SD), and after one night of sleep recovery (R).
We compared gene expression levels after six nights of habitual (22.30-07.00) or
extended (21.00-07.00) bedtimes. Using quantitative real-time PCR, the amount of
mRNA for A1R, A2AR, P2RX7, TNF-alpha, and IL-1beta was analyzed. After 24 h-SD
compared to B, whatever prior sleep condition, a significant increase of A2AR
expression was observed that returned to basal level after sleep recovery [day
main effect, F(2, 26) = 10.8, p < 0.001]. In both sleep condition, a day main
effect on P2RX7 mRNA was observed [F(2, 26) = 6.7, p = 0.005] with significant
increases after R compared with 24 h-SD. TNF-alpha and IL-1beta expressions were
not significantly altered. Before 24 h-SD (baseline), the A2AR expression was
negatively correlated with the latency of stage 3 sleep during the previous
night, while that of the A1R positively. This was not observed after sleep
recovery following 24 h-SD. This is the first study showing increased A2AR and
not A1 gene expression after 24 h-SD in leukocytes of healthy subjects, and this
even if bedtime was initially increased by 1.5 h per night for six nights. In
conclusion, prolonged wakefulness induced an up-regulation of the A2A receptor
gene expression in leukocytes from healthy subjects. Significant correlations
between baseline expression of A1 and A2A receptors in peripheral cells and stage
3 sleep suggested their involvement in mediating the effects of adenosine on
sleep.
PMID- 28512399
TI - Protein S Negatively Regulates Neural Stem Cell Self-Renewal through Bmi-1
Signaling.
AB - Revealing the molecular mechanisms underlying neural stem cell self-renewal is a
major goal toward understanding adult brain homeostasis. The self-renewing
potential of neural stem and progenitor cells (NSPCs) must be tightly regulated
to maintain brain homeostasis. We recently reported the expression of Protein S
(PROS1) in adult hippocampal NSPCs, and revealed its role in regulation of NSPC
quiescence and neuronal differentiation. Here, we investigate the effect of PROS1
on NSPC self-renewal and show that genetic ablation of Pros1 in neural
progenitors increased NSPC self-renewal by 50%. Mechanistically, we identified
the upregulation of the polycomb complex protein Bmi-1 and repression of its
downstream effectors p16Ink4a and p19Arf to promote NSPC self-renewal in Pros1
ablated cells. Rescuing Pros1 expression restores normal levels of Bmi-1
signaling, and reverts the proliferation and enhanced self-renewal phenotypes
observed in Pros1-deleted cells. Our study identifies PROS1 as a novel negative
regulator of NSPC self-renewal. We conclude PROS1 is instructive for NSPC
differentiation by negatively regulating Bmi-1 signaling in adult and embryonic
neural stem cells.
PMID- 28512400
TI - Exposure to Hedione Increases Reciprocity in Humans.
AB - Cooperation among unrelated humans is frequently regarded as a defining feature
in the evolutionary success of our species. Whereas, much research has addressed
the strategic and cognitive mechanisms that underlie cooperation, investigations
into chemosensory processes have received very limited research attention. To
bridge that gap, we build on recent research that has identified the chemically
synthesized odorant Hedione (HED) as a ligand for the putative human pheromone
receptor (VN1R1) expressed in the olfactory mucosa, and hypothesize that exposure
to HED may increase reciprocity. Applying behavioral economics paradigms, the
present research shows that exposure to the ligand causes differentiated
behavioral effects in reciprocal punishments (Study 1) as well as rewards (Study
2), two types of behaviors that are frequently regarded as essential for the
development and maintenance of cooperation.
PMID- 28512401
TI - Increased Gamma Connectivity in the Human Prefrontal Cortex during the
Bereitschaftspotential.
AB - The Bereitschaftspotential (BP) is a slow negative cortical potential preceding
voluntary movement. Since movement preparation is dependent upon the synchronous
activity of a variety of neurons, BP may develop through the exchange of
information among motor-related neurons. However, the relationship between BP and
information flow is not yet well-known. In the present study, we aimed to
investigate how the connectivity in the prefrontal cortex (PFC) changes during
the occurrence of BP. Electrocorticography (ECoG) was recorded in five patients
with epilepsy. The subjects performed self-paced hand grasping. We compared the
intraregional connectivity between PFC and non-PFC regions using partial directed
coherence. In the PFC, the connectivity of beta and gamma bands in the BP period
increased by an average of 24.4% compared with the baseline connectivity.
Conversely, gamma connectivity in non-PFC regions decreased by 31.4%. Moreover,
the intraregional connectivity in the PFC increased according to the stage of BP.
The increased gamma band connectivity in the PFC implies that the increased
communication among neurons in the PFC is associated with development of BP.
Intraregional connectivity as one of the factors involved in voluntary movement
may reflect the activation of brain networks related to movement preparation in
PFC.
PMID- 28512403
TI - Papulonodular Secondary Syphilis Presenting as Multiple Distinct Cutaneous
Lesions in an HIV-Positive Transgender Woman.
AB - We present the first reported case of papulonodular secondary syphilis in an HIV
positive transgender female. Syphilis is classified into primary, secondary,
latent, and tertiary stages, with secondary syphilis having notably diverse
cutaneous manifestations. Our patient presented with diverse lesions throughout
her body, all pathologically consistent with papulonodular secondary syphilis.
Proper identification of the multiple presentations of syphilis is crucial to
early diagnosis and treatment. This report seeks to broaden the scope of
dermatological manifestations that arise secondary to papulonodular syphilis in
HIV-positive patients.
PMID- 28512402
TI - Unilateral Linear Punctate Palmoplantar Keratoderma: A Case Report.
AB - Punctate palmoplantar keratoderma (PPPK) is a rare entity with an estimated
prevalence rate of 1.17/100,000. PPPK usually presents with bilateral
asymptomatic, tiny, hyperkeratotic punctate papules and plaques on the
palmoplantar surface. Among the PPPK varieties, the linear presentation is much
rarer, and so far there have been only 3 case reports. Here, we report the case
of a 27-year-old female Thai patient who presented to our outpatient clinic with
unilateral asymptomatic linear thickening lesions on her right sole since
childhood. There were no similar lesions on other parts of the body. A
histopathologic examination revealed epidermal hyperplasia and hyperkeratosis
without columns of parakeratosis or cornoid lamella. The other examinations were
normal. The clinical and histological contexts were consistent with a diagnosis
of unilateral linear PPPK. The patient was treated with topical 10% urea cream
and 10% salicylic acid cream twice daily. To the best of our knowledge, this is
the first reported case of unilateral linear PPPK in Thailand, and the fourth
reported case worldwide.
PMID- 28512404
TI - Painful Leg Ulceration in a Poorly Controlled Hypertensive Patient: A Case Report
of Martorell Ulcer.
AB - Martorell ulcer is a form of lower limb ulceration, preceded by a small area of
excruciating pain. It often appears as a solitary lesion on the outer aspect of
the lower limb, and is primarily associated with poorly controlled hypertension
and diabetes. Treatment of the ulcer involves awareness and early correct
diagnosis, adequate control of blood pressure, management of infection, and wound
care. We describe a 77-year-old diabetic and hypertensive woman presenting with
excruciating pain in her right lower lateral leg leading to a necrotic ulcer.
Serial photographs of the evolution of the lesion and eventual healing of the
ulcer are presented.
PMID- 28512398
TI - Protein Homeostasis in Amyotrophic Lateral Sclerosis: Therapeutic Opportunities?
AB - Protein homeostasis (proteostasis), the correct balance between production and
degradation of proteins, is essential for the health and survival of cells.
Proteostasis requires an intricate network of protein quality control pathways
(the proteostasis network) that work to prevent protein aggregation and maintain
proteome health throughout the lifespan of the cell. Collapse of proteostasis has
been implicated in the etiology of a number of neurodegenerative diseases,
including amyotrophic lateral sclerosis (ALS), the most common adult onset motor
neuron disorder. Here, we review the evidence linking dysfunctional proteostasis
to the etiology of ALS and discuss how ALS-associated insults affect the
proteostasis network. Finally, we discuss the potential therapeutic benefit of
proteostasis network modulation in ALS.
PMID- 28512406
TI - A Case of Subcutaneous Sarcoidosis Occurring along the Superficial Veins of the
Forearms: A Distinctive Cutaneous Manifestation Masquerading Venous Tropic Action
in the Underlying Systemic Disease?
AB - Sarcoidosis is a multisystem disease of unknown etiology, developing granulomas
in any tissues and organs. Approximately 25% of sarcoidosis patients have
cutaneous involvement with various clinical manifestations, which are categorized
into specific or nonspecific diseases based on the histopathology; the former
represents the typical sarcoid granulomas. Subcutaneous sarcoidosis is one of the
specific skin lesions and often affects extremities, to a much lesser extent with
other anatomical sites. Herein, we report the case of an 82-year-old Japanese man
with subcutaneous sarcoidosis whose skin nodules exclusively overlay the lines of
superficial veins on the forearms. This rare clinical presentation was discussed
with the literature reported thus far to access the underlying disease
pathophysiology from the viewpoint of tropic response to the venous system in
systemic sarcoidosis.
PMID- 28512405
TI - Concomitant B Hairy Cell Leukemia and Mycosis Fungoides in an Elderly Man.
AB - The development of both a T- and B-cell lymphoproliferative disorder in one
patient is an unlikely coincidence due to the low prevalence of each malignancy.
We report a 65-year-old man with a previously documented history of B hairy cell
leukemia, who presented with a new-onset acneiform eruption of his scalp, face,
trunk, back, and extremities. Routine pathology of the skin lesions with
immunohistochemical stains and molecular studies were consistent with a
folliculotropic mycosis fungoides. B hairy cell leukemia and mycosis fungoides
occurring in the same patient seems to be a rare phenomenon with only 5 cases
reported in the literature.
PMID- 28512407
TI - Severe Rhabdomyolysis during Treatment with Trabectedin in Combination with a
Herbal Drug in a Patient with Metastatic Synovial Sarcoma: A Case Report.
AB - Rhabdomyolysis is defined as dissolution of striped muscle characterized by
leakage of intracellular muscle components into the circulation, which can
ultimately lead to renal failure with a possible fatal outcome. This is an
uncommon side effect of trabectedin which is used in second-line therapy of
metastatic sarcoma after anthracycline and ifosfamide failure. Here, we describe
a case of reversible rhabdomyolysis in a male patient with recurrent metastatic
synovial sarcoma of the hand, with marked 18F-FDG uptake into his skeletal
muscles, after 4 cycles of trabectedin, and who at the same time was taking an
alternative medicine (bioflavonoids) suspected of triggering this adverse event.
PMID- 28512408
TI - Cytoreductive Surgery Followed by Hyperthermic Intraperitoneal Chemotherapy for
Recurrent Ovarian Cancer with Incidental Bochdalek Hernia and Postoperative
Bilateral Thalamic Infarct: A Case Report.
AB - Congenital Bochdalek hernia is a defect of the diaphragm and very rare in adults.
Only around 100 cases have been reported in the literature. Herein, we present a
case with a recurrent ovarian cancer who underwent secondary cytoreductive
surgery and hyperthermic intraperitoneal chemotherapy. An oval defect with
dimensions of 3 * 4 cm was seen in the left posterolateral site of the diaphragm
during surgical exploration. In addition, a 6 * 3 cm iatrogenic right-sided
diaphragmatic defect was found and repaired. In the early postoperative period, a
bilateral thalamic infarction occurred.
PMID- 28512409
TI - Immunoglobulin D Multiple Myeloma Presenting as Spontaneous Fracture.
AB - Immunoglobulin D multiple myeloma is a rare type of multiple myeloma that usually
presents as bone pain, fatigue, or weight loss. We report a case of
immunoglobulin D multiple myeloma in a 53-year-old Caucasian male patient with
previous medical history of anaplastic oligodendroglioma status post-surgical
resection who was evaluated for back pain while mowing the lawn. His physical
examination showed tenderness over the lower thoracic vertebrae with no sensory
or motor impairment. Initial lab investigations showed normocytic anemia and
hypercalcemia with low parathyroid hormone. Magnetic resonance imaging of
thoracic spine with and without contrast showed acute pathological fracture of
the T12 vertebral body with enhancing soft tissue which extended into the left
ventral epidural space and left T11-T12 neural foramen. Serum protein
electrophoresis showed abnormal protein band in the gamma globulin. Free light
chain assay showed serum free kappa which was elevated at 3,090.0 mg/L (reference
range 3.3-19.4 mg/L). Immunoglobulin D was elevated at 566.0 mg/dL (reference
range <15.3 mg/dL). The patient was successfully treated with standard
chemotherapy and autologous peripheral blood stem cell transplant with complete
remission 3 years after starting treatment. Advancement in the treatment of
immunoglobulin D multiple myeloma urge clinicians to offer their patients new
treatment options especially as of the earlier presentation of this subtype of
multiple myeloma and the previous reports of worse prognosis.
PMID- 28512411
TI - Spinal Intradural Intramedullary Dissemination in the Absence of Intracranial
Relapse of a Previously Radically Treated Temporal Lobe Glioblastoma Multiforme.
AB - Intracranial glioblastoma multiforme (GBM) constitutes the most frequent and
unfortunately aggressive primary central nervous system malignancy. Despite the
high tendency of these tumors to show local relapse within the brain after
primary therapy, dissemination into the spinal axis is an infrequent event. If
spinal metastases occur they are leptomeningeal in the vast majority of cases and
always in the context of intracranial progressive disease. Spinal intramedullary
metastases of intracranial GBM have rarely been described to date. We report the
unique case of a young woman with subacute progressive paraparesis due to spinal
intramedullary metastases of a temporal lobe GBM despite the remarkable absence
of intracranial tumor relapse. The patient had undergone gross total resection of
a left temporal GBM in contact with the ventricles and cisternal space followed
by radio- and chemotherapy 13 months before. At the moment of diagnosis of spinal
intramedullary metastases, there were no signs of intracranial tumor recurrence
as revealed by MRI scans. Since a high level of suspicion may be needed to detect
this rare evolution of intracranial GBM and other differential diagnoses must be
ruled out at presentation, we discuss the important features of this case
regarding clinical manifestation, diagnosis, surgery, and management.
Furthermore, we mention possible factors that may have contributed to the
development of these metastases in the context of intracranial remission.
PMID- 28512412
TI - Sudden Onset of Brain Metastasis despite the Use of Vemurafenib for Another
Metastatic Lesion in Malignant Melanoma Patients.
AB - Vemurafenib is an inhibitor of the BRAF mutation and has been approved by the
Food and Drug Administration as a treatment option for patients with unresectable
melanoma without brain metastasis. In the literature, vemurafenib has been
reported to be also effective against brain metastasis. We encountered 3 cases
with brain metastasis on vemurafenib therapy. In these cases, vemurafenib was
clinically effective against metastatic lesions other than those in the brain.
The brain lesions developed after the metastatic lesion had occurred. Therefore,
we assume that the melanomas of the patients acquired resistance against
vemurafenib. The brain metastases were treated with the cyberknife. Patients 1
and 2 without LDH elevation are still alive, but patient 3 with abnormal LDH
elevation died despite the treatment. We need to carefully follow patients on
vemurafenib therapy because brain metastasis can suddenly occur even if the
metastatic lesion has decreased clinically. The therapeutic effect of vemurafenib
against brain metastasis is poor in cases with LDH elevation.
PMID- 28512410
TI - RRx-001 Priming of PD-1 Inhibition in the Treatment of Small Cell Carcinoma of
the Vagina: A Rare Gynecological Tumor.
AB - Small cell carcinoma of the vagina is rare, so rare in fact that the total number
reported in English-language journals is less than 30. Due to this extremely low
incidence, no specific treatment guidelines have been established, and most of
what is clinically known is derived from a handful of single case reports.
However, as befitting its highly aggressive histologic features, which are
reminiscent of small cell lung cancer (SCLC), first-line treatment is modeled
after SCLC. Herein is reported the case of a 51-year-old African-American patient
with metastatic biopsy-proven small cell carcinoma of the vagina that progressed
through multiple therapies: first-line cisplatin and etoposide (making it
platinum-resistant) and radiotherapy, followed by the tumor macrophage
stimulating agent RRx-001 in a clinical trial called QUADRUPLE THREAT, which per
protocol preceded a mandated rechallenge with cisplatin and etoposide. RECIST
v.1.1 tumor progression on both RRx-001 and cisplatin/etoposide was accompanied
by central necrosis in several of the enlarged lymph nodes and hepatic
metastases, which may have been evidence of pseudoprogression, accounting for her
ongoing longer-than-expected survival, since the necrotic tissue may have primed
the activity of the PD-1 inhibitor. The lack of response to RRx-001 is
hypothesized to have correlated with sparse tumor macrophage infiltration, seen
on pre- and post-treatment biopsies, since the mechanism of action of RRx-001
relates to stimulation of tumor-associated macrophages.
PMID- 28512413
TI - Two Cases of Nivolumab Re-Administration after Pneumonitis as Immune-Related
Adverse Events.
AB - Nivolumab is a recently approved medication for the treatment of unresectable
malignant melanoma. Many immune-related adverse events (irAEs) associated with
nivolumab have been reported, such as pneumonitis, hepatitis, dermatitis, and
thyroiditis. Prednisolone can effectively treat irAEs. However, it is unclear how
or if nivolumab should be administered to patients after they have experienced an
irAE. Herein, we show 2 patients who underwent pneumonitis as irAE. Case 1
demonstrated a cryptogenic organizing pneumonia pattern in the CT scan and case 2
had a diffuse alveolar damage (DAD) pattern. Oral corticosteroids improved chest
shadow of CT scan in both cases. However, when nivolumab was re-administrated,
case 1 demonstrated no symptoms, but case 2 demonstrated pneumonia again. From
our cases, it is difficult to re-administrate nivolumab for the patients with
pneumonitis which shows a DAD pattern in CT, even if oral corticosteroids improve
their symptoms.
PMID- 28512414
TI - An Intra-Abdominal Desmoid Tumor, Embedded in the Pancreas, Preoperatively
Diagnosed as an Extragastric Growing Gastrointestinal Stromal Tumor.
AB - A 45-year-old woman was found to have a pancreatic tumor by abdominal ultrasound
performed for a medical check-up. Abdominal contrast-enhanced computed tomography
showed a hypovascular tumor measuring 30 mm in diameter in the pancreatic tail.
Endoscopic ultrasound-guided fine needle aspiration was performed. An
extragastric growing gastrointestinal stromal tumor was thereby diagnosed
preoperatively, and surgical resection was planned. Laparoscopic surgery was
attempted but conversion to open surgery was necessitated by extensive adhesions,
and distal pancreatectomy, splenectomy, and partial gastrectomy were performed.
The histological diagnosis was an intra-abdominal desmoid tumor. A desmoid tumor
is a fibrous soft tissue tumor arising in the fascia and musculoaponeurotic
tissues. It usually occurs in the extremities and abdominal wall, and only rarely
in the abdominal cavity. We experienced a case with an intra-abdominal desmoid
tumor that was histologically diagnosed after laparotomy, which had been
preoperatively diagnosed as an extragastric growing gastrointestinal stromal
tumor. Although rare, desmoid tumors should be considered in the differential
diagnosis of intra-abdominal tumors. Herein, we report this case with a
literature review.
PMID- 28512415
TI - Neoadjuvant Chemotherapy and Adjuvant Chemoradiation Therapy in the Treatment of
Resected Gastric Adenocarcinoma: A Case Series.
AB - The treatment of gastric cancer requires a multimodal approach to decrease the
risk of locoregional and distant recurrence. The optimal timing of chemotherapy,
surgery, and radiation therapy continues to be explored in ongoing trials. In the
United States, surgical resection is often followed by adjuvant chemoradiation
therapy or by a combination of neoadjuvant and adjuvant chemotherapy. Here we
report on 4 patients with resected gastric adenocarcinoma who were treated with a
combination of these 2 approaches, receiving neoadjuvant chemotherapy followed by
adjuvant chemoradiation therapy.
PMID- 28512417
TI - A Case of Paraneoplastic Cushing Syndrome Presenting as Hyperglycemic
Hyperosmolar Nonketotic Syndrome.
AB - Carcinoid tumors are neuroendocrine tumors that mainly arise in the
gastrointestinal tract, lungs, and bronchi. Bronchopulmonary carcinoids have been
associated with Cushing syndrome, which results from ectopic adrenocorticotrophic
hormone (ACTH) secretion. We report the case of a 65-year-old man, a colonel in
the US Air Force, with metastatic bronchopulmonary carcinoid tumors treated on a
clinical trial who was hospitalized for complaints of increasing thirst,
polydipsia, polyuria, weakness, and visual changes. Decompensated hyperglycemia
suggested a diagnosis of hyperglycemic hyperosmolar nonketotic syndrome (HHNS).
Additional findings, which included hypokalemia, hypernatremia, hypertension,
metabolic alkalosis, moon facies, and striae, raised a red flag for an ectopic
ACTH syndrome. Elevated ACTH levels confirmed Cushing syndrome. Treatment with a
fluid replacement and insulin drip resulted in immediate symptomatic improvement.
Cushing syndrome should be considered in carcinoid patients with physical
stigmata such as moon facies and striae. HHNS may be the presenting clinical
feature in patients with impaired glucose metabolism.
PMID- 28512416
TI - Unusual Case of Laryngeal Squamous Cell Carcinoma with Cervical Metastasis of a
Prostatic Adenocarcinoma: A Case Report.
AB - Brain and Head and neck metastases are rare in prostatic carcinoma patients. In
this report we present a very uncommon case of the concomitant occurrence of a
prostatic adenocarcinoma with neck metastases and an advanced laryngeal squamous
cell carcinoma without neck metastases. The presence of cervical lymph node
prostate adenocarcinoma metastasis concomitantly with a laryngeal squamous cell
carcinoma is at least intriguing and may remind us of a rare event called
"collision tumors". In this case we had the metastatization of 1 carcinoma to the
site of the drainage of another carcinoma, but we never found the 2 histological
types as close as requested to reach the definition of a collision tumor. This
emphasizes the need of histological verification of different sites of recurrence
when 2 or more primary cancers are known in a patient, particularly when the
treatments of those primary cancers vary widely.
PMID- 28512418
TI - Cushing's Syndrome, Cortisol, and Cognitive Competency: A Case Report.
AB - Glucocorticoids are associated with immunosuppression and neuropsychiatric
complications. We describe the case of a carcinoid patient with Cushing's
syndrome (CS) and neurocognitive impairment due to ectopic ACTH production who
developed sepsis and died because of his family's decision to withdraw antibiotic
treatment. This report is presented to illustrate the importance of advanced-care
planning in patients with CS.
PMID- 28512419
TI - Successful Treatment of Primary Cutaneous Peripheral T-Cell Lymphoma Presenting
Acquired Ichthyosis with Oral Bexarotene Monotherapy.
AB - Acquired ichthyosis (AI) is a reactive cutaneous manifestation that can be
associated with malignant hematological disease, including cutaneous T-cell
lymphoma (CTCL). Since it is difficult to distinguish AI from ichthyosiform
mycosis fungoides, to select the treatment for CTCL with ichthyosis-like
appearance and to evaluate its efficacy is sometimes challenging. In this report,
we describe a case of primary cutaneous peripheral T-cell lymphoma not otherwise
specified presenting AI successfully treated with oral bexarotene. In the present
case, the administration of oral bexarotene was not only effective for lymphoma
cells infiltrating ulcers and nodules, but it also eliminated AI.
PMID- 28512420
TI - A Case of Iris Melanocytoma Demonstrating Diffuse Melanocytic Proliferation with
Uncontrolled Intraocular Pressure.
AB - We report a rare case with histologically proven melanocytoma of the iris that
demonstrated diffuse melanocytic proliferation with uncontrolled secondary
glaucoma and investigate the etiology of the intraocular pressure elevation. The
patient was a 78-year-old man with a history of darkened iris of his left eye.
The intraocular pressure was 39 mm Hg. A slit-lamp examination showed a diffuse
darkened iris, and a gonioscopic examination revealed open angle with
circumferential heavy pigmentation. There was no pigment dispersion of the
anterior chamber and no pigment deposition of the cornea. We suspected malignant
ring melanoma in the left eye and enucleated it. The globe was examined with
light and electron microscopy. Light microscopy revealed the presence of heavily
pigmented tumor cells in the iris, ciliary body, trabecular meshwork, and
Schlemm's canal. A bleached preparation showed large tumor cells with central and
paracentral nuclei without mitosis. Electron microscopy of the trabecular
meshwork revealed melanin-bearing tumor cells invading the intertrabecular
spaces, and the melanin granules were not phagocytosed in the trabecular cells.
The mechanical obstruction of the aqueous flow by the tumor cells may be a major
cause of secondary glaucoma in eyes with iris melanocytoma presenting diffuse
proliferation.
PMID- 28512421
TI - When an Easy Thing Goes Wrong: Foreign Body Induced Granuloma-Associated
Scleritis Following Pterygium Surgery.
AB - PURPOSE: To report a case of pterygium surgery with conjunctival autograft
followed by focal necrotizing scleritis due to foreign body entrapment in the
scleral bed. CASE REPORT/RESULTS: This is a case report of a 76-years-old male
patient who underwent nasal pterygium surgery and developed focal necrotizing
scleritis secondary to foreign body entrapment under conjunctival autograft. One
month following surgery, slit-lamp examination demonstrated a progressive
thinning of the surgical area with focal inflammatory signs. A small synthetic
fiber was identified to be trapped under the graft. A second intervention was
performed with foreign body removal and a new conjunctival graft. Despite the
surgery, focal scleral melting continued to progress and the patient was placed
under systemic corticotherapy and submitted to amniotic membrane graft with
epithelial side up. During the follow-up period there was a good tissue response.
CONCLUSION: Despite being a safe and quick procedure, pterygium surgery can
sometimes elicit new challenges.
PMID- 28512422
TI - Acute Onset Ocular Hypotony after Coronary Artery Bypass Surgery.
AB - IMPORTANCE: The purpose of this case report is to evaluate risk factors
associated with post-coronary artery bypass graft (CABG) ocular hypotony compared
to post-CABG ischemic optic neuropathy. OBSERVATIONS: The patient described here
is a single case at the University of California, Irvine Medical Center, from
July 2016. This case demonstrates the rare incidence of acute post-CABG ocular
hypotony and vision loss in a patient with prior history of optic atrophy. Both
vision loss and hypotony resolved completely to baseline without intervention
within 3 days postoperatively. CONCLUSIONS AND RELEVANCE: Severe anemia and large
fluctuations in central venous pressure and blood pressure can occur in any
patient undergoing CABG surgery. These hemodynamic shifts can cause transient
ischemia to pressure controlling systems such as the ciliary body and reduce
episcleral venous pressure. Other risk factors for acute hypotony in the setting
of CABG surgery also include the use of hypertonic agents, cardiopulmonary
bypass, and intravenous anesthesia.
PMID- 28512423
TI - Refined Internal Limiting Membrane Inverted Flap Technique for Intractable
Macular Detachment with Optic Disc Pit.
AB - PURPOSE: To report a surgical technique for retinal detachment associated with
optic disc pit (ODP) by using an internal limiting membrane (ILM) inverted flap
as an obstacle between the vitreous cavity and subretinal space. CASE
PRESENTATION: A 43-year-old man presented with decreased visual acuity in the
right eye for 1 week due to macular detachment associated with ODP. After 2
unsuccessful surgeries, the retina was reattached by vitrectomy with an ILM
inverted flap onto the ODP. CONCLUSION: Covering the pit with an inverted ILM
flap is a reliable method for intercepting fluid from the vitreous cavity.
Immediate absorption of subretinal fluid may lead to early macular attachment.
This technique would be effective in managing ODP.
PMID- 28512424
TI - Optical Coherence Tomography Angiography of Retinal Microvascular Changes
Overlying Choroidal Nodules in Neurofibromatosis Type 1.
AB - PURPOSE: To report 3 cases of neurofibromatosis type 1 (NF1) with choroidal
nodules associated with retinal microvascular changes imaged with optical
coherence tomography angiography (OCTA). METHODS: Small case series in 3 NF1
patients. OCTA examinations were performed by a trained examiner (J.J.) after
pupillary dilation. A standard scan, centered over the macula measuring 6 * 6 mm
and 3 * 3 mm was obtained according to the findings on standard color
photography. Additional scans were obtained in the zones with microvascular
abnormalities. The segmentation provided by the machine software was used.
RESULTS: Corkscrew retinal vessels were observed in association with "placoid"
type choroidal nodules as shown by near-infrared reflectance imaging. In all
cases, multiple lesions were found. They were second- or third-order tortuous
vessels originating from the superior or inferior temporal veins. OCTA
demonstrated that the tortuous venules were located in the superficial capillary
plexus, and no abnormalities were found in the deep capillary plexus. DISCUSSION:
Corkscrew retinal vessels are part of a spectrum of retinal microvascular
alterations seen in association, sometimes overlying choroidal nodules in
patients with NF1 and are visualized in the superficial capillary plexus on OCTA.
We demonstrated with OCTA that they are not associated with flow loss or ischemia
in the superficial and deep capillary plexus. The link between the underlying
nodule remains unclear. Since neovascularization was described in choroidal
ganglioneuroma, we hypothesize that corresponding secretory substances from
Schwann cells, ganglion cells, or melanocytes in choroidal nodules might alter
the retinal vasculature. CONCLUSION: We report on 3 cases of NF1 with choroidal
nodules in association with retinal microvascular changes imaged with OCTA. OCTA
demonstrated preservation of the blood flow in the deep and superficial capillary
plexus of the retina. We hypothesize that angiogenic factors secreted by the
underlying choroidal nodules could have an effect on the retinal vasculature.
Further immunohistological studies in NF1 patients with choroidal nodules to
detect angiogenic factors (such as VEGF) are necessary to confirm this
hypothesis.
PMID- 28512425
TI - Long-Term Follow-Up of Polypoidal Choroidal Vasculopathy Secondary to Angioid
Streaks Treated by Intravitreal Aflibercept and Ranibizumab.
AB - PURPOSE: Angioid streaks (AS) are dehiscences in Bruch's membrane that may be
idiopathic or associated with numerous systemic illnesses. Polypoidal choroidal
vasculopathy (PCV) is an underdiagnosed exudative chorioretinopathy often
characterised by serosanguineous detachments of the pigmented epithelium. The use
of the anti-VEGF agents ranibizumab and aflibercept in the management of PCV
secondary to AS has not been previously documented. We report 3 patients with
active PCV secondary to AS, 1 of which had a family history of PCV secondary to
AS, not previously reported in the literature. All patients were symptomatic and
treated with intravitreal anti-VEGF therapy with and without combination
photodynamic therapy (PDT). METHODS: This is a long-term retrospective case
review of 3 eyes of 3 patients with AS and clinical features of PCV. The patients
were examined using fundoscopy, spectral domain optical coherence tomography,
fluorescein angiography, and indocyanine green angiography. All patients were
managed with intravitreal anti-VEGF using a treat-and-extend protocol according
to specific retreatment criteria. One patient had 1 session of PDT in combination
with anti-VEGF injections. RESULTS: The mean follow-up time in all patients was 4
years. In all 3 cases, the treatment resulted in improved visual acuity and
regression of active PCV lesions with a longer duration between injections.
CONCLUSION: The treat-and-extend protocol with intravitreal aflibercept or
ranibizumab with or without PDT is effective and safe for PCV secondary to AS.
PMID- 28512426
TI - Spontaneous Unilateral Subperiosteal Hematoma in the Orbit due to Self-Induced
Asphyxia: Unusual Cause of Unilateral Exophthalmos.
AB - BACKGROUND: To report an unusual case of subperiosteal bleeding of nontraumatic
etiology. CASE DESCRIPTION: A 48-year-old female presented with an acute
protrusion of the left eye after nonaccomplished suicide by means of asphyxia
using a cable around the neck. At the time of presentation, the MRI showed an
orbital subperiosteal hematoma causing an exophthalmos. After conservative
treatment, there was a complete remission of the lesion. CONCLUSION: Nontraumatic
subperiosteal bleedings without involvement of the intraocular structures and no
vision-threatening intraorbital changes should be treated conservatively.
PMID- 28512427
TI - Long-Term Clinical Course in a Patient with Complete Congenital Stationary Night
Blindness.
AB - BACKGROUND: This report describes a 45-year-old man with complete congenital
stationary night blindness (CSNB1) who has been followed up for 38 years. CASE:
The patient first visited our hospital as a 7-year-old boy with a complaint of
low visual acuity. Best corrected visual acuity (BCVA) was 0.5 in the right eye
and 0.6 in the left eye. The refractive error was approximately -5.0 D in both
eyes. The fundus showed only myopic changes. A bright-flash electroretinogram
(ERG) revealed a negative configuration. We diagnosed CSNB and corrected the
refractive error with glasses. We continued to monitor the ERG and various
waveform components as well as visual acuity and the appearance of the fundus.
All NYX exons were screened for a causative mutation by polymerase chain reaction
amplification, and direct sequencing was performed. RESULTS: By 10 years of age,
BCVA had increased to 0.8 on the right and 0.9 on the left, with little change
thereafter. The fundus continued to show only myopic changes. No changes were
seen in the amplitude or implicit time of the a-wave or b-wave or in the b/a-wave
ratio. A novel hemizygous insertion mutation, c.1205_1206insT,
p.(Glu404Argfs*89), was detected in exon 2 of the NYX gene. CONCLUSION: To our
knowledge, this is the longest follow-up of a patient with CSNB1. No changes in
the clinical course have been seen during follow-up. We believe that it is
important to continue observations and accumulate clinical data for prognostic
purposes on patients with CSNB1.
PMID- 28512428
TI - Type 3 Neovascularization Associated with Retinitis Pigmentosa.
AB - PURPOSE: To report a case of type 3 neovascular lesion in a patient with
retinitis pigmentosa (RP) complicated by macular edema. CASE REPORT: A 78-year
old man with a long follow-up for RP was referred for painless visual acuity
decrease in the right eye. Best-corrected visual acuity was 20/125 in the right
eye and 20/40 in the left. Fundus examination showed typical RP and macular edema
in both eyes. In the right eye, spectral domain optical coherence tomography
revealed a marked cystic macular edema associated with disruption of the Bruch
membrane/retinal pigment epithelium complex overlying a pigmentary epithelium
detachment, with a vascular structure which appeared to originate from the deep
capillary plexus and to be connected with the subretinal pigment epithelium
space. Optical coherence tomography angiography showed a high-flow vessel
infiltrating the outer retinal layers in the deep capillary plexus segmentation,
and a tuft-shaped, bright, high-flow network that seemed to be connected with the
subretinal pigment epithelium space in the outer retinal layer segmentation. This
presentation was consistent with an early type 3 neovascular lesion in the right
eye. CONCLUSION: Type 3 neovascularization may be considered a possible
complication of RP.
PMID- 28512429
TI - Reduced Prefrontal Short-Latency Afferent Inhibition in Older Adults and Its
Relation to Executive Function: A TMS-EEG Study.
AB - Combining transcranial magnetic stimulation (TMS) with electroencephalography
(EEG) allows for the assessment of various neurophysiological processes in the
human cortex. One of these paradigms, short-latency afferent inhibition (SAI), is
thought to be a sensitive measure of cholinergic activity. In a previous study,
we demonstrated the temporal pattern of this paradigm from both the motor (M1)
and dorsolateral prefrontal cortex (DLPFC) using simultaneous TMS-EEG recording.
The SAI paradigm led to marked modulations at N100. In this study, we aimed to
investigate the age-related effects on TMS-evoked potentials (TEPs) with the SAI
from M1 and the DLPFC in younger (18-59 years old) and older (>=60 years old)
participants. Older participants showed significantly lower N100 modulation in M1
SAI as well as DLPFC-SAI compared to the younger participants. Furthermore, the
modulation of N100 by DLPFC-SAI in the older participants correlated with
executive function as measured with the Trail making test. This paradigm has the
potential to non-invasively identify cholinergic changes in cortical regions
related to cognition in older participants.
PMID- 28512430
TI - CYP2D6 Phenotyping Using Urine, Plasma, and Saliva Metabolic Ratios to Assess the
Impact of CYP2D6*10 on Interindividual Variation in a Chinese Population.
AB - Purpose: Asian populations have around 40-60% frequency of reduced function
allele CYP2D6*10 compared to 1-2% in Caucasian populations. The wide range of
CYP2D6 enzyme activities in subjects with the CYP2D6*10 variant is a big concern
for clinical practice. The quantitative analysis measuring the impact of CYP2D6
enzyme activity as a result of one CYP2D6*10 allele or two CYP2D6*10 alleles has
not been reported in large Asian populations. Methods: A total of 421 healthy
Chinese subjects were genotyped for CYP2D6 by polymerase chain reaction and
direct DNA sequencing. A total of 235 subjects with CYP2D6*1/*1 (n = 22),
CYP2D6*1/*10 (n = 93), CYP2D6*10/*10 (n = 85), and CYP2D6*5/*10 (n = 35) were
phenotyped for CYP2D6 using dextromethorphan as the probe drug. Metabolic ratios
(MR) were calculated as the ratio of parent drug to metabolite in 0-3 h urine, 3
h plasma, and 3 h saliva for each sample type. Results: The urinary, plasma, or
salivary MRs increased successively in subjects with CYP2D6*1/*1, *1/*10,
*10/*10, and *5/*10 (all P < 0.001). In the normal metabolizer group, homozygous
CYP2D6*10/*10 decreased the CYP2D6 enzyme activity further than heterozygous
CYP2D6*1/*10. Urinary, plasma, and salivary MRs were highly correlated.
Conclusion: The normal metabolizer group calls for a more detailed
classification. The activity score system could more accurately predict enzyme
activity than by grouping a number of genotypes into a single phenotype group.
Single-point plasma samples and saliva samples could be used as alternative
phenotyping methods for clinical convenience.
PMID- 28512431
TI - Variable Ventilation Improved Respiratory System Mechanics and Ameliorated
Pulmonary Damage in a Rat Model of Lung Ischemia-Reperfusion.
AB - Lung ischemia-reperfusion injury remains a major complication after lung
transplantation. Variable ventilation (VV) has been shown to improve respiratory
function and reduce pulmonary histological damage compared to protective volume
controlled ventilation (VCV) in different models of lung injury induced by
endotoxin, surfactant depletion by saline lavage, and hydrochloric acid. However,
no study has compared the biological impact of VV vs. VCV in lung ischemia
reperfusion injury, which has a complex pathophysiology different from that of
other experimental models. Thirty-six animals were randomly assigned to one of
two groups: (1) ischemia-reperfusion (IR), in which the left pulmonary hilum was
completely occluded and released after 30 min; and (2) Sham, in which animals
underwent the same surgical manipulation but without hilar clamping. Immediately
after surgery, the left (IR-injured) and right (contralateral) lungs from 6
animals per group were removed, and served as non-ventilated group (NV) for
molecular biology analysis. IR and Sham groups were further randomized to one of
two ventilation strategies: VCV (n = 6/group) [tidal volume (VT) = 6 mL/kg,
positive end-expiratory pressure (PEEP) = 2 cmH2O, fraction of inspired oxygen
(FiO2) = 0.4]; or VV, which was applied on a breath-to-breath basis as a sequence
of randomly generated VT values (n = 1200; mean VT = 6 mL/kg), with a 30%
coefficient of variation. After 5 min of ventilation and at the end of a 2-h
period (Final), respiratory system mechanics and arterial blood gases were
measured. At Final, lungs were removed for histological and molecular biology
analyses. Respiratory system elastance and alveolar collapse were lower in VCV
than VV (mean +/- SD, VCV 3.6 +/- 1.3 cmH20/ml and 2.0 +/- 0.8 cmH20/ml, p =
0.005; median [interquartile range], VCV 20.4% [7.9-33.1] and VV 5.4% [3.1-8.8],
p = 0.04, respectively). In left lungs of IR animals, VCV increased the
expression of interleukin-6 and intercellular adhesion molecule-1 compared to NV,
with no significant differences between VV and NV. Compared to VCV, VV increased
the expression of surfactant protein-D, suggesting protection from type II
epithelial cell damage. In conclusion, in this experimental lung ischemia
reperfusion model, VV improved respiratory system elastance and reduced lung
damage compared to VCV.
PMID- 28512432
TI - Whole-Body Cryotherapy in Athletes: From Therapy to Stimulation. An Updated
Review of the Literature.
AB - Nowadays, whole-body cryotherapy is a medical physical treatment widely used in
sports medicine. Recovery from injuries (e.g., trauma, overuse) and after-season
recovery are the main purposes for application. However, the most recent studies
confirmed the anti-inflammatory, anti-analgesic, and anti-oxidant effects of this
therapy by highlighting the underlying physiological responses. In addition to
its therapeutic effects, whole-body cryotherapy has been demonstrated to be a
preventive strategy against the deleterious effects of exercise-induced
inflammation and soreness. Novel findings have stressed the importance of fat
mass on cooling effectiveness and of the starting fitness level on the final
result. Exposure to the cryotherapy somehow mimics exercise, since it affects
myokines expression in an exercise-like fashion, thus opening another possible
window on the therapeutic strategies for metabolic diseases such as obesity and
type 2 diabetes. From a biochemical point of view, whole-body cryotherapy not
always induces appreciable modifications, but the final clinical output (in terms
of pain, soreness, stress, and post-exercise recovery) is very often improved
compared to either the starting condition or the untreated matched group. Also,
the number and the frequency of sessions that should be applied in order to
obtain the best therapeutic results have been deeply investigated in the last
years. In this article, we reviewed the most recent literature, from 2010 until
present, in order to give the most updated insight into this therapeutic
strategy, whose rapidly increasing use is not always based on scientific
assumptions and safety standards.
PMID- 28512433
TI - Reported Hydration Beliefs and Behaviors without Effect on Plasma Sodium in
Endurance Athletes.
AB - Purpose: Little information is available on the association of hydration beliefs
and behaviors in endurance athletes and exercise-associated hyponatremia (EAH).
The aim of the present study was to determine hydration beliefs and behaviors in
endurance athletes. Method: A 100 and 38 recreational athletes [107 mountain
bikers (MTBers) and 31 runners] competing in seven different endurance and ultra
endurance races completed pre- and post-race questionnaires, and a subgroup of
113 (82%) participants (82 MTBers and 31 runners) also provided their blood
samples. Result: More than half of the participants had some pre-race (59%), mid
race (58%), and post-race (55%) drinking plan. However, the participants
simultaneously reported that temperature (66%), thirst (52%), and plan (37%)
affected their drinking behavior during the race. More experienced (years of
active sport: p = 0.002; number of completed races: p < 0.026) and trained (p =
0.024) athletes with better race performance (p = 0.026) showed a more profound
knowledge of EAH, nevertheless, this did not influence their planned hydration,
reported fluid intake, or post-race plasma sodium. Thirteen (12%) hyponatremic
participants did not differ in their hydration beliefs, race behaviors, or
reported fluid intake from those without post-race EAH. Compared to MTBers,
runners more often reported knowledge of the volumes of drinks offered at fluid
stations (p < 0.001) and information on how much to drink pre-race (p < 0.001),
yet this was not associated with having a drinking plan (p > 0.05). MTBers with
hydration information planned more than other MTBers (p = 0.004). In comparison
with runners, more MTBers reported riding with their own fluids (p < 0.001) and
planning to drink at fluid stations (p = 0.003). On the whole, hydration
information was positively associated with hydration planning (n = 138) (p =
0.003); nevertheless, the actual reported fluid intake did not differ between the
group with and without hydration information, or with and without a pre-race
drinking plan (p > 0.05). Conclusion: In summary, hydration beliefs and behaviors
in the endurance athletes do not appear to affect the development of asymptomatic
EAH.
PMID- 28512434
TI - Evaluation of a Rapid Anisotropic Model for ECG Simulation.
AB - State-of-the-art cardiac electrophysiology models that are able to deliver
physiologically motivated activation maps and electrocardiograms (ECGs) can only
be solved on high-performance computing architectures. This makes it nearly
impossible to adopt such models in clinical practice. ECG imaging tools typically
rely on simplified models, but these neglect the anisotropic electric
conductivity of the tissue in the forward problem. Moreover, their results are
often confined to the heart-torso interface. We propose a forward model that
fully accounts for the anisotropic tissue conductivity and produces the standard
12-lead ECG in a few seconds. The activation sequence is approximated with an
eikonal model in the 3d myocardium, while the ECG is computed with the lead-field
approach. Both solvers were implemented on graphics processing units and
massively parallelized. We studied the numerical convergence and scalability of
the approach. We also compared the method to the bidomain model in terms of ECGs
and activation maps, using a simplified but physiologically motivated geometry
and 6 patient-specific anatomies. The proposed methods provided a good
approximation of activation maps and ECGs computed with a bidomain model, in only
a few seconds. Both solvers scaled very well to high-end hardware. These methods
are suitable for use in ECG imaging methods, and may soon become fast enough for
use in interactive simulation tools.
PMID- 28512435
TI - The Role of Self-esteem and Fear of Negative Evaluation in Compulsive Buying.
AB - Compulsive buying is a relatively new addictive disorder that interferes with
everyday functioning and may result in serious psychological and financial
problems (1). A very few data are currently available regarding this behavioral
addiction. This study investigated gender differences in the relationships
between contingent self-esteem (CSE), fear of negative evaluation (FNE), and
compulsive buying. Participants included 240 Italian adults (170 females, M age =
33.80) who responded to self-report questionnaires. The results showed that women
scored higher on CSE and FNE scales than men. No gender differences were found in
compulsive buying tendencies. CSE and FNE were positively related to CB.
Furthermore, structural equation modeling confirmed the evidence on CSE as a
strong predictor of CB for both genders. Interestingly, FNE seems to play a
mediating role between CSE and compulsive buying behaviors only for women. These
findings highlight the importance of studying self-esteem in compulsive buying
tendencies to inquire more deeply into the underlying mechanisms of some
compulsive behaviors.
PMID- 28512437
TI - Behavioral Patterns in Special Education. Good Teaching Practices.
AB - Providing quality education means to respond to the diversity in the classroom.
The teacher is a key figure in responding to the various educational needs
presented by students. Specifically, special education professionals are of great
importance as they are the ones who lend their support to regular classroom
teachers and offer specialized educational assistance to students who require it.
Therefore, special education is different from what takes place in the regular
classroom, demanding greater commitment by the teacher. There are certain
behaviors, considered good teaching practices, which teachers have always been
connected with to achieve good teaching and good learning. To ensure that these
teachers are carrying out their educational work properly it is necessary to
evaluate. This means having appropriate instruments. The Observational Protocol
for Teaching Functions in Primary School and Special Education (PROFUNDO-EPE,
v.3., in Spanish) allows to capture behaviors from these professionals and
behavioral patterns that correspond to good teaching practices. This study
evaluates the behavior of two special education teachers who work with students
from different educational stages and educational needs. It reveals that the
analyzed teachers adapt their behavior according the needs and characteristics of
their students to the students responding more adequately to the needs presented
by the students and showing good teaching practices. The patterns obtained
indicate that they offer support, help and clear guidelines to perform the tasks.
They motivate them toward learning by providing positive feedback and they check
that students have properly assimilated the contents through questions or non
verbal supervision. Also, they provide a safe and reliable climate for learning.
PMID- 28512436
TI - Transition to Kindergarten: Negative Associations between the Emotional
Availability in Mother-Child Relationships and Elevated Cortisol Levels in
Children with an Immigrant Background.
AB - Background: The transition to child care is a challenging time in a child's life
and leads to elevated levels of cortisol. These elevations may be influenced by
the quality of the mother-child relationship. However, remarkably little is known
about cortisol production in response to the beginning of child care among
children-at-risk such as children with an immigrant background. However,
attending kindergarten or any other child day-care institution can for example
have a compensating effect on potential language deficits thus improving the
educational opportunities of these children. Method: Data of a subsample of N =
24 "hard-to-reach" mother-child dyads was collected in the context of the
psychoanalytic early prevention project FIRST STEPS. The project focuses on the
earliest integration of children with an immigrant background by supporting
parenting capacities in the critical phase of migration and early parenthood.
Children's hair cortisol concentration (HCC) was assessed 1 week before (mean age
= 38.77 months) and 3 months after kindergarten entry (mean age = 42.26 months).
Hair analysis was conducted for both times of measurement, reflecting the first 3
months after kindergarten entry and 3 months prior. Furthermore, the emotional
quality of the mother-child relationship was assessed with the help of the
Emotional Availability Scales (EAS; Biringen, 2008) shortly before kindergarten
entry when the children were about 3 years old (mean age = 37.2). Results and
Conclusion: Children's mean cumulated HCC was higher after kindergarten entry
than before. The increase correlated negatively with several dimensions of the
EAS. Repeated measures ANCOVA revealed that particularly responsive children and
children who had experienced less intrusive mother-child relationships
demonstrated lower elevations in HCC after kindergarten entry. Furthermore, a
decreased EA score was found in all EA dimensions, besides the dimension
"mother's non-hostility," indicating problematic EA within the mother-child
relationships of the sample. The results suggest that children with an immigrant
background who experience more emotional available mother-child relationships
seem to regulate stress induced by kindergarten entry more effectively, indicated
by lower cortisol elevations after entry. This implicates that supporting early
mother-child relationships by intervention may have a positive effect on the
children's ability to regulate stress induced by kindergarten entry thus
promoting child development.
PMID- 28512438
TI - Are Neurodynamic Organizations A Fundamental Property of Teamwork?
AB - When performing a task it is important for teams to optimize their strategies and
actions to maximize value and avoid the cost of surprise. The decisions teams
make sometimes have unintended consequences and they must then reorganize their
thinking, roles and/or configuration into corrective structures more appropriate
for the situation. In this study we ask: What are the neurodynamic properties of
these reorganizations and how do they relate to the moment-by-moment, and longer,
performance-outcomes of teams?. We describe an information-organization approach
for detecting and quantitating the fluctuating neurodynamic organizations in
teams. Neurodynamic organization is the propensity of team members to enter into
prolonged (minutes) metastable neurodynamic relationships as they encounter and
resolve disturbances to their normal rhythms. Team neurodynamic organizations
were detected and modeled by transforming the physical units of each team
member's EEG power levels into Shannon entropy-derived information units about
the team's organization and synchronization. Entropy is a measure of the
variability or uncertainty of information in a data stream. This physical unit to
information unit transformation bridges micro level social coordination events
with macro level expert observations of team behavior allowing multimodal
comparisons across the neural, cognitive and behavioral time scales of teamwork.
The measures included the entropy of each team member's data stream, the overall
team entropy and the mutual information between dyad pairs of the team. Mutual
information can be thought of as periods related to team member synchrony.
Comparisons between individual entropy and mutual information levels for the dyad
combinations of three-person teams provided quantitative estimates of the
proportion of a person's neurodynamic organizations that represented periods of
synchrony with other team members, which in aggregate provided measures of the
overall degree of neurodynamic interactions of the team. We propose that
increased neurodynamic organization occurs when a team's operating rhythm can no
longer support the complexity of the task and the team needs to expend energy to
re-organize into structures that better minimize the "surprise" in the
environment. Consistent with this hypothesis, the frequency and magnitude of
neurodynamic organizations were less in experienced military and healthcare teams
than they were in more junior teams. Similar dynamical properties of neurodynamic
organization were observed in models of the EEG data streams of military,
healthcare and high school science teams suggesting that neurodynamic
organization may be a common property of teamwork. The innovation of this study
is the potential it raises for developing globally applicable quantitative models
of team dynamics that will allow comparisons to be made across teams, tasks and
training protocols.
PMID- 28512439
TI - Long-Time Exposure to Violent Video Games Does Not Show Desensitization on
Empathy for Pain: An fMRI Study.
AB - As a typical form of empathy, empathy for pain refers to the perception and
appraisal of others' pain, as well as the corresponding affective responses.
Numerous studies investigated the factors affecting the empathy for pain, in
which the exposure to violent video games (VVGs) could change players' empathic
responses to painful situations. However, it remains unclear whether exposure to
VVG influences the empathy for pain. In the present study, in terms of the
exposure experience to VVG, two groups of participants (18 in VVG group, VG; 17
in non-VVG group, NG) were screened from nearly 200 video game experience
questionnaires. And then, the functional magnetic resonance imaging data were
recorded when they were viewing painful and non-painful stimuli. The results
showed that the perception of others' pain were not significantly different in
brain regions between groups, from which we could infer that the desensitization
effect of VVGs was overrated.
PMID- 28512440
TI - Clinical Depression and Punishment Sensitivity on the BART.
AB - Depression is associated with altered sensitivity to reward and punishment, which
can influence complex decision-making. We examined punishment sensitivity in the
performance of participants with major depressive disorder (MDD) with that of a
comparison group on the automatic Balloon Analogue Risk Task (BART), which is a
direct measure of risk taking. The present study examined the BART performance of
30 individuals with MDD and 30 matched comparison individuals. The comparison
group (M = 63.25) entered a significantly (p < 0.001; d = 1.1) higher number of
pumps on the BART than the MDD group (M = 50.83). Higher levels of depression
symptoms were significantly correlated (r = -0.40, p < 0.05) with entering a
lower number of pumps in the MDD group. MDD patients showed an increased
sensitivity to punishment on the BART: after a loss, the MDD group decreased (M =
13.7) the number of subsequent pumps they entered by a significantly (p < 0.001,
d = 0.81) greater amount than the comparison group (M = 4.35). This difference
applied to losses only: no difference was found between the groups regarding the
magnitude of change in pumps selected after a win. Findings suggest the presence
of elevated punishment sensitivity among individuals with MDD, which may
contribute to the maintenance of depressive symptoms.
PMID- 28512441
TI - Mapping the Paths from Styles of Anger Experience and Expression to Obsessive
Compulsive Symptoms: The Moderating Roles of Family Cohesion and Adaptability.
AB - Previous research has shown strong connections of anger experience and expression
with obsessive-compulsive (OC) symptoms. Additionally, studies have demonstrated
links between family environment variables and obsessive-compulsive disorder
(OCD). Our study aims to integrate the perspectives from these two literatures by
exploring the moderating roles of family cohesion and family adaptability in the
relationship between anger proneness and suppression and OCD symptoms. A total of
2008 college students were recruited from a comprehensive university in Shanghai,
China between February and May 2016. The subjects completed self-report
inventories, including the Symptom Check List-90, State-Trait Anger Expression
Inventory 2 (Chinese version), and Family Adaptability and Cohesion Scale, second
edition (Chinese Version). Controlling for age, one-child family status,
ethnicity, family income, current depression, and anxiety, our analyses showed
that the association between anger proneness and OC symptoms was moderated by
family cohesion among men and that family adaptability moderated the connection
between anger suppression and OC complaints among women. The findings imply that
a more cohesive and empathic family environment may protect male students with
high levels of anger proneness from developing OC behaviors or thoughts. The
results suggest that for female subjects who are accustomed to suppressing angry
feelings, flexible family coping strategies and communication atmospheres would
reduce their vulnerability to OC symptoms. The findings are somewhat consistent
with those of previous studies on psychotherapy outcomes that showed that OCD
patients benefitted from psychotherapeutic interventions that cultivated the
clients' family cohesion and adaptability.
PMID- 28512442
TI - Posterior-Anterior Brain Maturation Reflected in Perceptual, Motor and Cognitive
Performance.
AB - Based on several postmortem morphometric and in vivo imaging studies it has been
postulated that brain maturation roughly follows a caudal to rostral direction.
In this study, we linked this maturational pattern to psychological function
employing a series of well-established behavioral tasks. We addressed three
distinct functions and brain regions with a perceptual (contour integration, CI),
motor (finger tapping, FT), and executive control (Navon global-local) task. Our
purpose was to investigate basic visual integration functions relying on primary
visual cortex (V1) in CI; motor coordination function related to primary motor
cortex (M1) in FT, and the executive control component, switching, related to the
dorsolateral prefrontal region of the brain in the Navon task. 122 volunteer
subjects were recruited to participate in this study between the ages of 10 and
20 (females n = 63, males n = 59). Employing conventional statistical methods, we
found that 10 and 12 year olds are performing significantly weaker than 20 year
olds in all three tasks. In the CI and Navon global-local tasks, even 14 years
old perform poorer than adults. We have also investigated the developmental
trajectories by fitting sigmoid curves on our data streams. The analysis of the
developmental trajectories of the three tasks showed a posterior to anterior
pattern in the emergence of the developmental functions with the earliest
development in the visual CI task (V1), followed by motor development in the FT
task (M1), and cognitive development as measured in the Navon global-local task
(DLPC) being the slowest. Gender difference was also present in FT task showing
an earlier maturation for girls in the motor domain.
PMID- 28512443
TI - Transcranial Direct Current Stimulation for Post-Concussion Syndrome: Study
Protocol for a Randomized Crossover Trial.
AB - BACKGROUND: Mild traumatic brain injury (MTBI) represents 70-80% of all treated
brain injuries. A considerable proportion of MTBI patients experience post
concussion symptoms for a prolonged period after MTBI, and these symptoms are
diagnosed as persistent post-concussion syndrome (PPCS). PPCS is defined as a
range of physical, cognitive, and emotional symptoms. However, memory and
executive dysfunction seems to be one of the most debilitating symptoms.
Recently, non-invasive brain stimulation has been studied as a potential
treatment method for traumatic brain injury (TBI) patients. Therefore, our
primary goal is to verify the effects of transcranial direct current stimulation
(tDCS) in patients with PPCS who demonstrate cognitive deficits in long-term
episodic memory, working memory, and executive function following MTBI.
METHODS/DESIGN: This is a randomized crossover trial of patients with a history
of MTBI with cognitive deficits in memory and executive function. Thirty adult
patients will be randomized in a crossover manner to receive three weekly
sessions of anodal tDCS (2 mA) at left dorsolateral prefrontal cortex, left
temporal cortex, and sham stimulation that will be performed at 7-day intervals
(washout period). The clinical diagnosis of PPCS will be determined using the
Rivermead Post-Concussion Symptoms Questionnaire. Patients who meet the inclusion
criteria will be assessed with a neuropsychological evaluation. A new battery of
computerized neuropsychological tests will be performed before and immediately
after each stimulation. Statistical analysis will be performed to determine
trends of cognitive improvement. DISCUSSION: There is paucity of studies
regarding the use of tDCS in TBI patients, and although recent results showed
controversial data regarding the effects of tDCS in such patients, we will
address specifically patients with PPCS and MTBI and no brain abnormalities on CT
scan other than subarachnoid hemorrhage. Moreover, due to the missing information
on literature regarding the best brain region to be studied, we will evaluate two
different regions to find immediate effects of tDCS on memory and executive
dysfunction. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier
NCT02292589 (https://register.clinicaltrials.gov).
PMID- 28512445
TI - The Therapeutic Value of Bone Marrow-Derived Endothelial Progenitor Cell
Transplantation after Intracerebral Hemorrhage in Rats.
AB - AIMS: To study the effect of endothelial progenitor cell (EPC) treatment on
intracerebral hemorrhage (ICH) in rats and elucidate possible mechanisms.
METHODS: The rats were randomly divided into three groups: (1) EPC group: ICH +
EPC, (2) phosphate-buffered saline group: ICH + PBS, and (3) sham group. EPCs
were transplanted intravenously 6 h after ICH. Modified neurological severity
score was used to evaluate neurological function. Blood-brain barrier (BBB)
integrity was evaluated. Dead cells, inflammatory cytokines, and neuroprotective
cytokines were assessed to investigate possible mechanisms. RESULTS: The animals
in the EPC group showed significant improvement in neurological function at 48 h,
72 h, and 7 days after ICH, compared with those in the PBS group. EPC
transplantation significantly reduced brain edema and the number of dead cells in
the hematoma boundary areas. The intensity of Evans Blue was decreased, and
expression levels of zonula occluden-1 and claudin-5 were increased in the EPC
group. Proinflammatory cytokines, including interferon-gamma, IL-6, and TNF
alpha, were decreased, whereas anti-inflammatory cytokines, including
transforming growth factor-beta1 and IL-10, were increased in the EPC group. In
addition, expression levels of brain-derived neurotrophic factor, vascular
endothelial growth factor, and neurotrophic growth factor were increased
following transplantation of EPCs. CONCLUSION: EPC transplantation could improve
neurological function of ICH rats. The protective effect may be mediated by
promotion of neuroprotective cytokine secretion, restoration of the BBB,
reduction of cell death, and the decrease in inflammation.
PMID- 28512444
TI - Longitudinal Quantification of Eye-Movement Impairments after Pontine Hemorrhage.
AB - INTRODUCTION: We report a case of hypertrophic olivary degeneration due to
pontine hemorrhage. A 59-year-old male with untreated hypertension suffered a
primary pontine hemorrhage, which caused horizontal eye-movement limitation.
Progressive neurological deterioration with involuntary eye and palatal movements
began months after hemorrhage. This was accompanied by magnetic resonance imaging
evidence of hypertrophic olivary degeneration at 4.5 months. BACKGROUND: Primary
pontine hemorrhage often leads to impairment of eye movements and diplopia.
Hypertrophic olivary degeneration can also emerge months after hemorrhage,
producing involuntary pendular eye movements. Neither the natural history of
voluntary eye movements nor the emergence of involuntary eye movements after
pontine hemorrhage has been previously quantified. METHODS: We used an
optokinetic task that enabled measurement of eye movements. It provided real-time
feedback on the ability to track continuously and saccade quickly in a pursuit
task. The feedback motivated the patient to use the system repeatedly in his
home. From 3 months after hemorrhage, the patient used the system for 9 months,
allowing us to quantify changes in his eye movements. RESULTS: Horizontal gaze
impairments were manifest in our task as limitation in horizontal range of
motion, as well as delay in initiation of the right eye's movement during left-to
right pursuit. Improvement in these impairments was measured over the course of
months 3-7 post hemorrhage. In addition, the emergence of vertical pendular
nystagmus was identified in the subject at 4 months. Analysis of the eye-movement
records revealed presymptomatic oscillatory eye movements whose amplitude had
grown steadily over the course of 3 weeks, prior to a sharp increase in amplitude
that coincided with the patient's first report of oscillopsia. Horizontal
pendular nystagmus emerged 7.4 months after the hemorrhage, primarily in the left
eye. CONCLUSION: An eye-tracking system deployed in a patient's home enabled
prospective longitudinal quantification of the natural history and improvement in
voluntary eye-movement impairments after pontine hemorrhage. It also
characterized prospectively for the first time, the emergence of involuntary eye
movements resulting from the rare complication of hypertrophic olivary
degeneration. Results suggest that brief weekly measurements with an eye-tracker
may allow early detection of this complication.
PMID- 28512446
TI - Neuroprotective Roles of l-Cysteine in Attenuating Early Brain Injury and
Improving Synaptic Density via the CBS/H2S Pathway Following Subarachnoid
Hemorrhage in Rats.
AB - l-Cysteine is a semi-essential amino acid and substrate for cystathionine-beta
synthase (CBS) in the central nervous system. We previously reported that NaHS,
an H2S donor, significantly alleviated brain damage after subarachnoid hemorrhage
(SAH) in rats. However, the potential therapeutic value of l-cysteine and the
molecular mechanism supporting these beneficial effects have not been determined.
This study was designed to investigate whether l-cysteine could attenuate early
brain injury following SAH and improve synaptic function by releasing endogenous
H2S. Male Wistar rats were subjected to SAH induced by cisterna magna blood
injection, and l-cysteine was intracerebroventricularly administered 30 min after
SAH induction. Treatment with l-cysteine stimulated CBS activity in the
prefrontal cortex (PFC) and H2S production. Moreover, l-cysteine treatment
significantly ameliorated brain edema, improved neurobehavioral function, and
attenuated neuronal cell death in the PFC; these effects were associated with a
decrease in the Bax/Bcl-2 ratio and the suppression of caspase-3 activation 48 h
after SAH. Furthermore, l-cysteine treatment activated the CREB-brain-derived
neurotrophic factor (BDNF) pathway and intensified synaptic density by regulating
synapse proteins 48 h after SAH. Importantly, all the beneficial effects of l
cysteine in SAH were abrogated by amino-oxyacetic acid, a CBS inhibitor. Based on
these findings, l-cysteine may play a neuroprotective role in SAH by inhibiting
cell apoptosis, upregulating CREB-BDNF expression, and promoting synaptic
structure via the CBS/H2S pathway.
PMID- 28512448
TI - The Potential Role of Contraction-Induced Myokines in the Regulation of Metabolic
Function for the Prevention and Treatment of Type 2 Diabetes.
AB - Skeletal muscle represents the largest organ in the body, comprises 36-42% of
body weight, and has recently been recognized as having an endocrine function.
Proteins expressed and released by muscle that have autocrine, paracrine, and
endocrine bioactivities have been termed myokines. It is likely that muscle
contraction represents the primary stimulus for the synthesis and secretion of
myokines to enable communication with other organs such as the liver, adipose
tissue, brain, and auto-regulation of muscle metabolism. To date, several hundred
myokines in the muscle secretome have been identified, a sub-population of which
are specifically induced by skeletal muscle contraction. However, the bioactivity
of many of these myokines and the mechanism through which they act has either not
yet been characterized or remains poorly understood. Physical activity and
exercise are recognized as a central tenet in both the prevention and treatment
of type 2 diabetes (T2D). Recent data suggest humoral factors such as muscle
derived secretory proteins may mediate the beneficial effects of exercise in the
treatment of metabolic diseases. This mini-review aims to summarize our current
knowledge on the role of contraction-induced myokines in mediating the beneficial
effects of physical activity and exercise in the prevention and treatment of T2D,
specifically glucose and lipid metabolism. Future directions as to how we can
optimize contraction-induced myokine secretion to inform exercise protocols for
the prevention and treatment of T2D will also be discussed.
PMID- 28512447
TI - Low-Dose Pulsatile Interleukin-6 As a Treatment Option for Diabetic Peripheral
Neuropathy.
AB - Diabetic peripheral neuropathy (DPN) remains one of the most common and serious
complications of diabetes. Currently, pharmacological agents are limited to
treating the pain associated with DPN, and do not address the underlying
pathological mechanisms driving nerve damage, thus leaving a significant unmet
medical need. Interestingly, research conducted using exercise as a treatment for
DPN has revealed interleukin-6 (IL-6) signaling to be associated with many
positive benefits such as enhanced blood flow and lipid metabolism, decreased
chronic inflammation, and peripheral nerve fiber regeneration. IL-6, once known
solely as a pro-inflammatory cytokine, is now understood to signal as a
multifunctional cytokine, capable of eliciting both pro- and anti-inflammatory
responses in a context-dependent fashion. IL-6 released from muscle in response
to exercise signals as a myokine and as such has a unique kinetic profile,
whereby levels are transiently elevated up to 100-fold and return to baseline
levels within 4 h. Importantly, this kinetic profile is in stark contrast to long
term IL-6 elevation that is associated with pro-inflammatory states. Given
exercise induces IL-6 myokine signaling, and exercise has been shown to elicit
numerous beneficial effects for the treatment of DPN, a causal link has been
suggested. Here, we discuss both the clinical and preclinical literature related
to the application of IL-6 as a treatment strategy for DPN. In addition, we
discuss how IL-6 may directly modulate Schwann and nerve cells to explore a
mechanistic understanding of how this treatment elicits a neuroprotective and/or
regenerative response. Collectively, studies suggest that IL-6, when administered
in a low-dose pulsatile strategy to mimic the body's natural response to
exercise, may prove to be an effective treatment for the protection and/or
restoration of peripheral nerve function in DPN. This review highlights the
studies supporting this assertion and provides rationale for continued
investigation of IL-6 for the treatment of DPN.
PMID- 28512449
TI - Antibacterial Potential of an Antimicrobial Agent Inspired by Peroxidase
Catalyzed Systems.
AB - Antibiotic resistance is an increasingly serious threat to global health.
Consequently, the development of non-antibiotic based therapies and
disinfectants, which avoid induction of resistance, or cross-resistance, is of
high priority. We report the synthesis of a biocidal complex, which is produced
by the reaction between ionic oxidizable salts-iodide and thiocyanate-in the
presence of hydrogen peroxide as an oxidation source. The reaction generates
bactericidal reactive oxygen and iodine species. In this study, we report that
the iodo-thiocyanate complex (ITC) is an effective bactericidal agent with
activity against planktonic and biofilm cells of Gram-negative (Escherichia coli
and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus and
methicillin-resistant S. aureus) bacteria. The minimum bactericidal
concentrations and the minimum biofilm eradication concentrations of the biocidal
composite were in the range of 7.8-31.3 and 31.3-250 MUg ml-1, respectively. As a
result, the complex was capable to cause a rapid cell death of planktonic test
cultures at between 0.5 and 2 h, and complete eradication of dual and mono
species biofilms between 30 s and 10 min. Furthermore, the test bacteria,
including a MRSA strain, exposed to the cocktail failed to develop resistance
after serial passages. The antimicrobial activity of the ITC appears to derive
from the combinational effect of the powerful species capable of oxidizing the
essential biomolecules of bacteria. The use of this composition may provide an
effective and efficient method for killing potential pathogens, as well as for
disinfecting and removing biofilm contamination.
PMID- 28512450
TI - Host Plant Compatibility Shapes the Proteogenome of Frankia coriariae.
AB - Molecular signaling networks in the actinorhizal rhizosphere select host
compatible Frankia strains, trigger the infection process and eventually the
genesis of nitrogen-fixing nodules. The molecular triggers involved remain
difficult to ascertain. Root exudates (RE) are highly dynamic substrates that
play key roles in establishing the rhizosphere microbiome. RE are known to induce
the secretion by rhizobia of Nod factors, polysaccharides, and other proteins in
the case of legume symbiosis. Next-generation proteomic approach was here used to
decipher the key bacterial signals matching the first-step recognition of host
plant stimuli upon treatment of Frankia coriariae strain BMG5.1 with RE derived
from compatible (Coriaria myrtifolia), incompatible (Alnus glutinosa), and non
actinorhizal (Cucumis melo) host plants. The Frankia proteome dynamics were
mainly driven by host compatibility. Both metabolism and signal transduction were
the dominant activities for BMG5.1 under the different RE conditions tested. A
second set of proteins that were solely induced by C. myrtifolia RE and were
mainly linked to cell wall remodeling, signal transduction and host signal
processing activities. These proteins may footprint early steps in receptive
recognition of host stimuli before subsequent events of symbiotic recruitment.
PMID- 28512452
TI - Towards Identifying Protective B-Cell Epitopes: The PspA Story.
AB - Pneumococcal surface protein A (PspA) is one of the most abundant cell surface
protein of Streptococcus pneumoniae (S. pneumoniae). PspA variants are
structurally and serologically diverse and help evade complement-mediated
phagocytosis of S. pneumoniae, which is essential for its survival in the host.
PspA is currently been screened for employment in the generation of more
effective (serotype independent) vaccine to overcome the limitations of
polysaccharide based vaccines, providing serotype specific immune responses. The
cross-protection eliciting regions of PspA localize to the alpha-helical and
proline rich regions. Recent data indicate significant variation in the ability
of antibodies induced against the recombinant PspA variants to recognize distinct
S. pneumoniae strains. Hence, screening for the identification of the
topographical repertoire of B-cell epitopes that elicit cross-protective immune
response seems essential in the engineering of a superior PspA-based vaccine.
Herein, we revisit epitope identification in PspA and the utility of hybridoma
technology in directing the identification of protective epitope regions of PspA
that can be used in vaccine research.
PMID- 28512453
TI - Alterations in the Rumen Liquid-, Particle- and Epithelium-Associated Microbiota
of Dairy Cows during the Transition from a Silage- and Concentrate-Based Ration
to Pasture in Spring.
AB - In spring dairy cows are often gradually transitioned from a silage- and
concentrate-based ration (total mixed ration, TMR) to pasture. Rumen microbiota
adaptability is a key feature of ruminant survival strategy. However, only little
is known on the temporal and spatial microbial alterations involved. This study
aims to investigate how the rumen liquid (LAAB), particle (PAAB), and epithelium
(EAAB) associated archaea and bacteria are influenced by this nutritional change.
A 10-wk trial was performed, including 10 rumen-fistulated dairy cows, equally
divided into a pasture- and a confinement- group (PG and CG). The CG stayed on a
TMR-based ration, while the PG was gradually transitioned from TMR to pasture (wk
1: TMR-only, wk 2: 3 h/day on pasture, wk 3 & 4: 12 h/day on pasture, wk 5-10:
pasture-only). In wk 1, wk 5, and wk 10 samples of solid and liquid rumen
contents, and papillae biopsies were collected. The DNA was isolated, and PCR
SSCP and 16S rRNA gene amplicon sequencing analysis were performed. Cluster
analysis revealed a higher similarity between LAAB and PAAB, compared to the
EAAB, characterized by higher species diversity. At all three locations the
microbiota was significantly influenced by the ration change, opposite the
generally acknowledged hypothesis that the EAAB remain more consistent throughout
dietary changes. Even though the animals in the PG were already on a full-grazing
ration for 4-6 days in wk 5, the microbiota at all three locations was
significantly different compared to wk 10, suggesting an adaptation period of
several days to weeks. This is in line with observations made on animal level,
showing a required time for adaptation of 2-3 weeks for production and metabolic
variables. A large part of the rumen prokaryote species remained unaltered upon
transition to pasture and exhibited a strong host influence, supporting the
hypothesis that the rumen microbiota consists of a core and a variable
microbiota. For the effect of the location as well as the ration change either
very similar or opposite trends among member species of common taxa were
observed, demonstrating that microbes that are phylogenetically close may still
exhibit substantially different phenotypes and functions.
PMID- 28512451
TI - Colonization and Succession within the Human Gut Microbiome by Archaea, Bacteria,
and Microeukaryotes during the First Year of Life.
AB - Perturbations to the colonization process of the human gastrointestinal tract
have been suggested to result in adverse health effects later in life. Although
much research has been performed on bacterial colonization and succession, much
less is known about the other two domains of life, archaea, and eukaryotes. Here
we describe colonization and succession by bacteria, archaea and microeukaryotes
during the first year of life (samples collected around days 1, 3, 5, 28, 150,
and 365) within the gastrointestinal tract of infants delivered either vaginally
or by cesarean section and using a combination of quantitative real-time PCR as
well as 16S and 18S rRNA gene amplicon sequencing. Sequences from organisms
belonging to all three domains of life were detectable in all of the collected
meconium samples. The microeukaryotic community composition fluctuated strongly
over time and early diversification was delayed in infants receiving formula
milk. Cesarean section-delivered (CSD) infants experienced a delay in
colonization and succession, which was observed for all three domains of life.
Shifts in prokaryotic succession in CSD infants compared to vaginally delivered
(VD) infants were apparent as early as days 3 and 5, which were characterized by
increased relative abundances of the genera Streptococcus and Staphylococcus, and
a decrease in relative abundance for the genera Bifidobacterium and Bacteroides.
Generally, a depletion in Bacteroidetes was detected as early as day 5 postpartum
in CSD infants, causing a significantly increased Firmicutes/Bacteroidetes ratio
between days 5 and 150 when compared to VD infants. Although the delivery mode
appeared to have the strongest influence on differences between the infants,
other factors such as a younger gestational age or maternal antibiotics intake
likely contributed to the observed patterns as well. Our findings complement
previous observations of a delay in colonization and succession of CSD infants,
which affects not only bacteria but also archaea and microeukaryotes. This
further highlights the need for resolving bacterial, archaeal, and
microeukaryotic dynamics in future longitudinal studies of microbial colonization
and succession within the neonatal gastrointestinal tract.
PMID- 28512454
TI - New Insights into the Regulation of Cell-Surface Signaling Activity Acquired from
a Mutagenesis Screen of the Pseudomonas putida IutY Sigma/Anti-Sigma Factor.
AB - Cell-surface signaling (CSS) is a signal transfer system that allows Gram
negative bacteria to detect environmental signals and generate a cytosolic
response. These systems are composed of an outer membrane receptor that senses
the inducing signal, an extracytoplasmic function sigma factor (sigmaECF) that
targets the cytosolic response by modifying gene expression and a cytoplasmic
membrane anti-sigma factor that keeps the sigmaECF in an inactive state in the
absence of the signal and transduces its presence from the outer membrane to the
cytosol. Although CSS systems regulate bacterial processes as crucial as stress
response, iron scavenging and virulence, the exact mechanisms that drive CSS are
still not completely understood. Binding of the signal to the CSS receptor is
known to trigger a signaling cascade that results in the regulated proteolysis of
the anti-sigma factor and the activation of the sigmaECF in the cytosol. This
study was carried out to generate new insights in the proteolytic activation of
CSS sigmaECF. We performed a random mutagenesis screen of the unique IutY protein
of Pseudomonas putida, a protein that combines a cytosolic sigmaECF domain and a
periplasmic anti-sigma factor domain in a single polypeptide. In response to the
presence of an iron carrier, the siderophore aerobactin, in the extracellular
medium, IutY is processed by two different proteases, Prc and RseP, which results
in the release and activation of the sigmaIutY domain. Our experiments show that
all IutY mutant proteins that contain periplasmic residues depend on RseP for
activation. In contrast, Prc is only required for mutant variants with a
periplasmic domain longer than 50 amino acids, which indicates that the
periplasmic region of IutY is trimmed down to ~50 amino acids creating the RseP
substrate. Moreover, we have identified several conserved residues in the CSS
anti-sigma factor family of which mutation leads to constitutive activation of
their cognate sigmaECF. These findings advance our knowledge on how CSS activity
is regulated by the consecutive action of two proteases. Elucidation of the exact
mechanism behind CSS activation will enable the development of strategies to
block CSS in pathogenic bacteria.
PMID- 28512455
TI - Non-edible Oil Cakes as a Novel Substrate for DPA Production and Augmenting
Biocontrol Activity of Paecilomyces variotii.
AB - The present study investigated the use of waste non-edible oil cakes (Jatropha,
Karanja, Neem, and Mahua) as a substrate for the growth of Paecilomyces variotii
and dipicolinic acid (DPA) production. Previous researches proved the efficacy of
DPA in suppressing certain pathogens that are deleterious to the plants in the
rhizosphere. DPA production was statistical optimized by amending non-edible oil
cakes in growing media as nitrogen and sugars (Dextrose, Glucose, and Lactose) as
carbon source. Plackett-Burman design (PBD), indicated that Jatropha cake,
Karanja cake, and Dextrose were the most significant components (p < 0.05) of the
media and were further optimized using response surface methodology (RSM).
Jatropha cake, Karanja cake, and Dextrose at the concentration of 12.5, 4.5, and
10 g/l, respectively, yielded 250 mg/l of DPA, which was 2.5 fold more than that
obtained from basal medium. HPLC analysis of the optimized medium (peak at
retention time of 30 min) confirmed the enhanced DPA production by P. variotii.
The scanning electron microscopy (SEM) images showed that optimized medium impose
a stress like condition (due to less C:N ratio) for the fungus and generated more
spores as compared to the basal medium in which carbon source is easily available
for the mycelial growth. The antimicrobial activity of the fungal extract was
tested and found to be effective even at 10-2 dilution after 72 h against two
plant pathogens, Fusarium oxysporum and Verticillium dahlia. Statistical
experimental design of this study and the use of non-edible oil cakes as a
substrate offer an efficient and viable approach for DPA production by P.
variotii.
PMID- 28512456
TI - Proline-Based Cyclic Dipeptides from Korean Fermented Vegetable Kimchi and from
Leuconostoc mesenteroides LBP-K06 Have Activities against Multidrug-Resistant
Bacteria.
AB - Lactobacillus plantarum and Leuconostoc mesenteroides play a prominent role as
functional starters and predominant isolates in the production of various types
of antimicrobial compound-containing fermented foods, especially including
kimchi. In the case of the bioactive cyclic dipeptides, their racemic
diastereomers inhibitory to bacteria and fungi have been suggested to come solely
from Lactobacillus spp. of these strains. We previously demonstrated the
antifungal and antiviral activities of proline-based cyclic dipeptides, which
were fractionated from culture filtrates of Lb. plantarum LBP-K10 originated from
kimchi. However, cyclic dipeptides have not been identified in the filtrates,
either from cultures or fermented subject matter, driven by Ln. mesenteroides,
which have been widely used as starter cultures for kimchi fermentation. Most
importantly, the experimental verification of cyclic dipeptide-content changes
during kimchi fermentation have also not been elucidated. Herein, the
antibacterial fractions, including cyclo(Leu-Pro) and cyclo(Phe-Pro), from Ln.
mesenteroides LBP-K06 culture filtrates, which exhibited a typical
chromatographic retention behavior (tR), were identified by using semi
preparative high-performance liquid chromatography and gas chromatography-mass
spectrometry. Based on this finding, the proline-based cyclic dipeptides,
including cyclo(Ser-Pro), cyclo(Tyr-Pro), and cyclo(Leu-Pro), were additionally
identified in the filtrates only when fermenting Chinese cabbage produced with
Ln. mesenteroides LBP-K06 starter cultures. The detection and isolation of cyclic
dipeptides solely in controlled fermented cabbage were conducted under the
control of fermentation-process parameters concomitantly with strong CDP
selectivity by using a two-consecutive-purification strategy. Interestingly,
cyclic dipeptides in the filtrates, when using this strain as a starter,
increased with fermentation time. However, no cyclic dipeptides were observed in
the filtrates of other fermented products, including other types of kimchi and
fermented materials of plant and animal origin. This is the first report to
conclusively demonstrate evidence for the existence of antimicrobial cyclic
dipeptides produced by Ln. mesenteroides in kimchi. Through filtrates from lactic
acid bacterial cultures and from fermented foods, we have also proved a method of
combining chromatographic fractionation and mass spectrometry-based analysis for
screening cyclic dipeptide profiling, which may allow evaluation of the fermented
dairy foods from a new perspective.
PMID- 28512457
TI - The 25-26 nt Small RNAs in Phytophthora parasitica Are Associated with Efficient
Silencing of Homologous Endogenous Genes.
AB - Small RNAs (sRNAs) are important non-coding RNA regulators, playing key roles in
developmental regulation, transposon suppression, environmental response, host
pathogen interaction and other diverse biological processes. However, their roles
in oomycetes are poorly understood. Here, we performed sRNA sequencing and RNA
sequencing of Phytophthora parasitica at stages of vegetative growth and
infection of Arabidopsis roots to examine diversity and function of sRNAs in P.
parasitica, a model hemibiotrophic oomycete plant pathogen. Our results indicate
that there are two distinct types of sRNA-generating loci in P. parasitica
genome, giving rise to clusters of 25-26 nt and 21 nt sRNAs, respectively, with
no significant strand-biases. The 25-26 nt sRNA loci lie predominantly in gene
sparse and repeat-rich regions, and overlap with over 7000 endogenous gene loci.
These overlapped genes are typically P. parasitica species-specific, with no
homologies to the sister species P. infestans. They include approximately 40%
RXLR effector genes, 50% CRN effector genes and some elicitor genes. The
transcripts of most of these genes could not be detected at both the vegetative
mycelium and infection stages as revealed by RNA sequencing, indicating that the
25-26 nt sRNAs are associated with efficient silencing of these genes. The 21 nt
sRNA loci typically overlap with the exon regions of highly expressed genes,
suggesting that the biogenesis of the 21 nt sRNAs may be dependent on the level
of gene transcription and that these sRNAs do not mediate efficient silencing of
homologous genes. Analyses of the published P. infestans sRNA and mRNA sequencing
data consistently show that the 25-26 nt sRNAs, but not the 21 nt sRNAs, may
mediate efficient gene silencing in Phytophthora.
PMID- 28512458
TI - A Mitochondrial Autonomously Replicating Sequence from Pichia pastoris for
Uniform High Level Recombinant Protein Production.
AB - Pichia pastoris is a non-conventional methylotrophic yeast that is widely used
for recombinant protein production, typically by stably integrating the target
gene into the genome as part of an expression cassette. However, the
comparatively high clonal variability associated with this approach usually
necessitates a time intense screening step in order to find strains with the
desired productivity. Some of the factors causing this clonal variability can be
overcome using episomal vectors containing an autonomously replicating sequence
(ARS). Here, we report on the discovery, characterization, and application of a
fragment of mitochondrial DNA from P. pastoris for use as an ARS. First
encountered as an off-target event in an experiment aiming for genomic
integration, the newly created circular plasmid named "pMito" consists of the
expression cassette and a fragment of mitochondrial DNA. Multiple matches to
known ARS consensus sequence motifs, but no exact match to known chromosomal ARS
from P. pastoris were detected on the fragment, indicating the presence of a
novel ARS element. Different variants of pMito were successfully used for
transformation and their productivity characteristics were assayed. All analyzed
clones displayed a highly uniform expression level, exceeding by up to fourfold
that of a reference with a single copy integrated in its genome. Expressed GFP
could be localized exclusively to the cytoplasm via super-resolution fluorescence
microscopy, indicating that pMito is present in the nucleus. While expression
levels were homogenous among pMito clones, an apparent upper limit of expression
was visible that could not be explained based on the gene dosage. Further
investigation is necessary to fully understand the bottle-neck hindering this and
other ARS vectors in P. pastoris from reaching their full capability. Lastly, we
could demonstrate that the mitochondrial ARS from P. pastoris is also suitable
for episomal vector transformation in Saccharomyces cerevisiae, widening the
potential for biotechnological application. pMito displayed strong potential to
reduce clonal variability in experiments targeting recombinant protein
production. These findings also showcase the as of yet largely untapped potential
of mitochondrial ARS from different yeasts for biotechnological applications.
PMID- 28512459
TI - In Vivo Chronic Stimulation Unveils Autoreactive Potential of Wiskott-Aldrich
Syndrome Protein-Deficient B Cells.
AB - Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency caused by mutations
in the gene encoding the hematopoietic-specific WAS protein (WASp). WAS is
frequently associated with autoimmunity, indicating a critical role of WASp in
maintenance of tolerance. The role of B cells in the induction of autoreactive
immune responses in WAS has been investigated in several settings, but the
mechanisms leading to the development of autoimmune manifestations have been
difficult to evaluate in the mouse models of the disease that do not
spontaneously develop autoimmunity. We performed an extensive characterization of
Was-/- mice that provided evidence of the potential alteration in B cell
selection, because of the presence of autoantibodies against double-stranded DNA,
platelets, and tissue antigens. To uncover the mechanisms leading to the
activation of the potentially autoreactive B cells in Was-/- mice, we performed
in vivo chronic stimulations with toll-like receptors agonists (LPS and CpG) and
apoptotic cells or infection with lymphocytic choriomeningitis virus. All
treatments led to increased production of autoantibodies, increased proteinuria,
and kidney tissue damage in Was-/- mice. These findings demonstrate that a lower
clearance of pathogens and/or self-antigens and the resulting chronic
inflammatory state could cause B cell tolerance breakdown leading to autoimmunity
in WAS.
PMID- 28512460
TI - Immunological Aspect of Radiation-Induced Pneumonitis, Current Treatment
Strategies, and Future Prospects.
AB - Delivery of high doses of radiation to thoracic region, particularly with non
small cell lung cancer patients, becomes difficult due to subsequent
complications arising in the lungs of the patient. Radiation-induced pneumonitis
is an early event evident in most radiation exposed patients observed within 2-4
months of treatment and leading to fibrosis later. Several cytokines and
inflammatory molecules interplay in the vicinity of the tissue developing
radiation injury leading to pneumonitis and fibrosis. While certain cytokines may
be exploited as biomarkers, they also appear to be a potent target of
intervention at transcriptional level. Initiation and progression of pneumonitis
and fibrosis thus are dynamic processes arising after few months to year after
irradiation of the lung tissue. Currently, available treatment strategies are
challenged by the major dose limiting complications that curtails success of the
treatment as well as well being of the patient's future life. Several approaches
have been in practice while many other are still being explored to overcome such
complications. The current review gives a brief account of the immunological
aspects, existing management practices, and suggests possible futuristic
approaches.
PMID- 28512463
TI - Allometric Models for Predicting Aboveground Biomass and Carbon Stock of Tropical
Perennial C4 Grasses in Hawaii.
AB - Biomass is a promising renewable energy option that provides a more
environmentally sustainable alternative to fossil resources by reducing the net
flux of greenhouse gasses to the atmosphere. Yet, allometric models that allow
the prediction of aboveground biomass (AGB), biomass carbon (C) stock non
destructively have not yet been developed for tropical perennial C4 grasses
currently under consideration as potential bioenergy feedstock in Hawaii and
other subtropical and tropical locations. The objectives of this study were to
develop optimal allometric relationships and site-specific models to predict AGB,
biomass C stock of napiergrass, energycane, and sugarcane under cultivation
practices for renewable energy and validate these site-specific models against
independent data sets generated from sites with widely different environments.
Several allometric models were developed for each species from data at a low
elevation field on the island of Maui, Hawaii. A simple power model with stalk
diameter (D) was best related to AGB and biomass C stock for napiergrass,
energycane, and sugarcane, (R2 = 0.98, 0.96, and 0.97, respectively). The models
were then tested against data collected from independent fields across an
environmental gradient. For all crops, the models over-predicted AGB in plants
with lower stalk D, but AGB was under-predicted in plants with higher stalk D.
The models using stalk D were better for biomass prediction compared to dewlap H
(Height from the base cut to most recently exposed leaf dewlap) models, which
showed weak validation performance. Although stalk D model performed better,
however, the mean square error (MSE)-systematic was ranged from 23 to 43 % of MSE
for all crops. A strong relationship between model coefficient and rainfall was
existed, although these were irrigated systems; suggesting a simple site-specific
coefficient modulator for rainfall to reduce systematic errors in water-limited
areas. These allometric equations provide a tool for farmers in the tropics to
estimate perennial C4 grass biomass and C stock during decision-making for land
management and as an environmental sustainability indicator within a renewable
energy system.
PMID- 28512461
TI - Transcriptional Responses to Pre-flowering Leaf Defoliation in Grapevine Berry
from Different Growing Sites, Years, and Genotypes.
AB - Leaf removal is a grapevine canopy management technique widely used to modify the
source-sink balance and/or microclimate around berry clusters to optimize fruit
composition. In general, the removal of basal leaves before flowering reduces
fruit set, hence achieving looser clusters, and improves grape composition since
yield is generally curtailed more than proportionally to leaf area itself. Albeit
responses to this practice seem quite consistent, overall vine performance is
affected by genotype, environmental conditions, and severity of treatment. The
physiological responses of grape varieties to defoliation practices have been
widely investigated, and just recently a whole genome transcriptomic approach was
exploited showing an extensive transcriptome rearrangement in berries defoliated
before flowering. Nevertheless, the extent to which these transcriptomic
reactions could be manifested by different genotypes and growing environments is
entirely unexplored. To highlight general responses to defoliation vs. different
locations, we analyzed the transcriptome of cv. Sangiovese berries sampled at
four development stages from pre-flowering defoliated vines in two different
geographical areas of Italy. We obtained and validated five markers of the early
defoliation treatment in Sangiovese, an ATP-binding cassette transporter, an
auxin response factor, a cinnamyl alcohol dehydrogenase, a flavonoid 3-O
glucosyltransferase and an indole-3-acetate beta-glucosyltransferase. Candidate
molecular markers were also obtained in another three grapevine genotypes (Nero
d'Avola, Ortrugo, and Ciliegiolo), subjected to the same level of selective pre
flowering defoliation (PFD) over two consecutive years in their different areas
of cultivation. The flavonol synthase was identified as a marker in the pre
veraison phase, the jasmonate methyltransferase during the transition phase and
the abscisic acid receptor PYL4 in the ripening phase. The characterization of
transcriptome changes in Sangiovese berry after PFD highlights, on one hand, the
stronger effect of environment than treatment on the whole berry transcriptome
rearrangement during development and, on the other, expands existing knowledge of
the main molecular and biochemical modifications occurring in defoliated vines.
Moreover, the identification of candidate genes associated with PFD in different
genotypes and environments provides new insights into the applicability and
repeatability of this crop practice, as well as its possible agricultural and
qualitative outcomes across genetic and environmental variability.
PMID- 28512464
TI - Insights into the Mechanism of Proliferation on the Special Microbes Mediated by
Phenolic Acids in the Radix pseudostellariae Rhizosphere under Continuous
Monoculture Regimes.
AB - As potent allelochemicals, phenolic acids are believed to be associated with
replanting disease and cause microflora shift and structural disorder in the
rhizosphere soil of continuously monocultured Radix pseudostellariae. The
transcriptome sequencing was used to reveal the mechanisms underlying the
differential response of pathogenic bacterium Kosakonia sacchari and beneficial
bacterium Bacillus pumilus on their interactions with phenolic acids, the main
allelochemicals in root exudates of R. pseudostellariae in the monoculture
system. The microbes were inoculated in the pots containing soil and the
medicinal plant in this study. The results showed that the addition of beneficial
B. pumilus to the 2-year planted soil significantly decreased the activity of
soil urease, catalase, sucrase, and cellulase and increased the activity of
chitinase compared with those in the 2nd-year monocropping rhizosphere soil
without any treatment. However, opposite results were obtained when K. sacchari
was added. Transcriptome analysis showed that vanillin enhanced
glycolysis/gluconeogenesis, fatty acid biosynthesis, pentose phosphate, bacterial
chemotaxis, flagellar assembly, and phosphotransferase system pathway in K.
sacchari. However, protocatechuic acid, a metabolite produced by K. sacchari from
vanillin, had negative effects on the citrate cycle and biosynthesis of
novobiocin, phenylalanine, tyrosine, and tryptophan in B. pumilus. Concurrently,
the protocatechuic acid decreased the biofilm formation of B. pumilus. These
results unveiled the mechanisms how phenolic acids differentially mediate the
shifts of microbial flora in rhizosphere soil, leading to the proliferation of
pathogenic bacteria (i.e., K. sacchari) and the attenuation of beneficial
bacteria (i.e., B. pumilus) under the monocropping system of R. pseudostellariae.
PMID- 28512465
TI - Growth, Water Use, and Nitrate-15N Uptake of Greenhouse Tomato as Influenced by
Different Irrigation Patterns, 15N Labeled Depths, and Transplant Times.
AB - Increasing water use efficiency and reducing nitrogen pollutant discharge are
important tasks for modern agriculture. To evaluate the effect of alternate
partial root-zone irrigation (APRI) on tomato plant growth, water use efficiency
and nitrate-15N uptake, an experiment was conducted from June to December in 2014
under greenhouse condition in northern China. The experiment contained two
irrigation patterns [APRI and conventional irrigation (CI)], two 15N labeled
depths in soil (10 and 50 cm) and two transplant time (early and late summer).
Results showed that, compared to CI, APRI did not significantly (p > 0.05) impact
the growth and biomass accumulation in aboveground part of tomato, while it
enhanced the root, reflecting by greater length density, and more dry mass. APRI
produced marginally lower yields, but saved 34.9% of irrigation water, and gave a
37.6-49.9% higher water use efficiency relative to CI. In addition, APRI improved
fruit quality, mainly through increasing the contents of soluble solid (by 12.8
21.6%), and vitamin C (2.8-12.7%), and the sugar/acid ratio (3.5-8.5%). The 15N
utilization efficiency (15NUE) in APRI was higher than that in CI, which was more
evident when 15N was labeled at 50 cm depth. Significant (p < 0.05) 15N recovery
increase of 10.2-13.2% and 15N loss decrease of 35.4-54.6% were found for APRI
compared to CI. The overall results suggest that APRI under greenhouse could
benefit the nitrate-N recovery and increase the water use efficiency in tomato.
PMID- 28512462
TI - De novo Transcriptome Profiling of Flowers, Flower Pedicels and Pods of Lupinus
luteus (Yellow Lupine) Reveals Complex Expression Changes during Organ
Abscission.
AB - Yellow lupine (Lupinus luteus L., Taper c.), a member of the legume family
(Fabaceae L.), has an enormous practical importance. Its excessive flower and pod
abscission represents an economic drawback, as proper flower and seed formation
and development is crucial for the plant's productivity. Generative organ
detachment takes place at the basis of the pedicels, within a specialized group
of cells collectively known as the abscission zone (AZ). During plant growth
these cells become competent to respond to specific signals that trigger
separation and lead to the abolition of cell wall adhesion. Little is known about
the molecular network controlling the yellow lupine organ abscission. The aim of
our study was to establish the divergences and similarities in transcriptional
networks in the pods, flowers and flower pedicels abscised or maintained on the
plant, and to identify genes playing key roles in generative organ abscission in
yellow lupine. Based on de novo transcriptome assembly, we identified 166,473
unigenes representing 219,514 assembled unique transcripts from flowers, flower
pedicels and pods undergoing abscission and from control organs. Comparison of
the cDNA libraries from dropped and control organs helped in identifying 1,343,
2,933 and 1,491 differentially expressed genes (DEGs) in the flowers, flower
pedicels and pods, respectively. In DEG analyses, we focused on genes involved in
phytohormonal regulation, cell wall functioning and metabolic pathways. Our
results indicate that auxin, ethylene and gibberellins are some of the main
factors engaged in generative organ abscission. Identified 28 DEGs common for all
library comparisons are involved in cell wall functioning, protein metabolism,
water homeostasis and stress response. Interestingly, among the common DEGs we
also found an miR169 precursor, which is the first evidence of micro RNA engaged
in abscission. A KEGG pathway enrichment analysis revealed that the identified
DEGs were predominantly involved in carbohydrate and amino acid metabolism, but
some other pathways were also targeted. This study represents the first
comprehensive transcriptome-based characterization of organ abscission in L.
luteus and provides a valuable data source not only for understanding the
abscission signaling pathway in yellow lupine, but also for further research
aimed at improving crop yields.
PMID- 28512466
TI - Salinity Stress Does Not Affect Root Uptake, Dissemination and Persistence of
Salmonella in Sweet-basil (Ocimum basilicum).
AB - Crop produce can be contaminated in the field during cultivation by bacterial
human pathogens originating from contaminated soil or irrigation water. The
bacterial pathogens interact with the plant, can penetrate the plant via the root
system and translocate and survive in above-ground tissues. The present study is
first to investigate effects of an abiotic stress, salinity, on the interaction
of plants with a bacterial human pathogen. The main sources of human bacterial
contamination of plants are manures and marginal irrigation waters such as
treated or un-treated wastewater. These are often saline and induce
morphological, chemical and physiological changes in plants that might affect the
interaction between the pathogens and the plant and thereby the potential for
plant contamination. This research studied effects of salinity on the
internalization of the bacterial human pathogen Salmonella enterica serovar
Newport via the root system of sweet-basil plants, dissemination of the bacteria
in the plant, and kinetics of survival in planta. Irrigation with 30 mM NaCl
salinity induced typical salt-stress effects on the plant: growth was reduced, Na
and Cl concentrations increased, K and Ca concentrations reduced, osmotic
potential and anti-oxidative activity were increased by 30%, stomatal conductance
was reduced, and concentrations of essential-oils in the plants increased by 26%.
Despite these physical, chemical and morphological changes in the plants, root
internalization of the bacteria and its translocation to the shoot were not
affected, and neither was the die-off rate of Salmonella in planta. The results
demonstrate that the salinity-induced changes in the sweet-basil plants did not
affect the interaction between Salmonella and the plant and thereby the potential
for crop contamination.
PMID- 28512468
TI - Molecular Identification and Karyological Analysis of a Rampant Aspen Populus
tremula L. (Salicaceae) Clone.
AB - A rampant highly heterozygous aspen (Populus tremula L.) clone "Meshabash" has
been revealed in course of population genetic diversity analysis in a native
stand in the Republic of Tatarstan, Russia. Here we report the results of
karyological analysis showing that this highly vigorous clone is diploid (2n =
38) while typically triploid aspen demonstrates increased growth rate and
resistance to aspen trunk rot caused by fungus Phellinus tremulae. By means of
DNA identification of a series of model trees using 14 SSR loci we outlined the
area occupied by this clone (at least 1.94 ha) and demonstrated that its ramets
constitute 40 out of 48 genotyped trunks on the plot with the maximal distance
between ramets 254 m. Since aspen is able to regenerate after cutting or die-off
of maternal tree by root suckers at a distance up to 20-35 m this assumed that
current stand appeared as a result of such spreading from an ortet tree during at
least 5 generations. Trunk rot damage in the wood of model trees indicated low
influence of this pathogen on viability and performance of the studied clone that
can be associated with its extreme heterozygosity level (0.926) exceeding all the
studied trees in this research plot and in three other control samples.
PMID- 28512467
TI - Extra Facial Landmark Localization via Global Shape Reconstruction.
AB - Localizing facial landmarks is a popular topic in the field of face analysis.
However, problems arose in practical applications such as handling pose
variations and partial occlusions while maintaining moderate training model size
and computational efficiency still challenges current solutions. In this paper,
we present a global shape reconstruction method for locating extra facial
landmarks comparing to facial landmarks used in the training phase. In the
proposed method, the reduced configuration of facial landmarks is first
decomposed into corresponding sparse coefficients. Then explicit face shape
correlations are exploited to regress between sparse coefficients of different
facial landmark configurations. Finally extra facial landmarks are reconstructed
by combining the pretrained shape dictionary and the approximation of sparse
coefficients. By applying the proposed method, both the training time and the
model size of a class of methods which stack local evidences as an appearance
descriptor can be scaled down with only a minor compromise in detection accuracy.
Extensive experiments prove that the proposed method is feasible and is able to
reconstruct extra facial landmarks even under very asymmetrical face poses.
PMID- 28512470
TI - Predictors of Cephalic Vaginal Delivery Following External Cephalic Version: An
Eight-Year Single-Centre Study of 447 Cases.
AB - Introduction. Our study aims to investigate and evaluate (1) rates of success of
ECV for breech presentation at term at the Royal Women's Hospital in comparison
to international standards; (2) mode of delivery following ECV; (3) factors
influencing success rates of ECV at the Royal Women's Hospital. Methods. An audit
of all women who underwent ECV between the years 2007 and 2014 at the Royal
Women's Hospital as public patients was completed. Data parameters were collected
from paper and electronic patient files at the Women's Hospital. Data was
collected to analyse the effect of the following parameters on ECV success and
birth outcome: age, parity, gestational age, BMI, AFI, and tocolytic use. These
parameters were analysed to determine their effect on ECV outcome and birth
outcome. Results. The Women's Hospital, Melbourne, has an ECV success rate of
approximately 37%. Of the patients undergoing ECV, 29% proceeded to normal
vaginal delivery. Predictors of successful ECV included low BMI, multiparity, and
AFI more than 16 (P < 0.05). The only predictor of cephalic vaginal delivery
following ECV was multiparity. Negative predictors of cephalic delivery were low
AFI and nulliparity. Conclusions. The success rate of ECV at the Women's
Hospital, Melbourne, is in line with global standards.
PMID- 28512469
TI - Metabolic Perturbation and Potential Markers in Patients with Esophageal Cancer.
AB - Clinical diagnosis of esophageal cancer (EC) at early stage is rather difficult.
This study aimed to profile the molecules in serum and tissue and identify
potential biomarkers in patients with EC. A total of 64 volunteers were
recruited, and 83 samples (24 EC serum samples, 21 serum controls, 19 paired EC
tissues, and corresponding tumor-adjacent tissues) were analyzed. The gas
chromatography time-of-flight mass spectrometry (GC/TOF-MS) was employed, and
principal component analysis was used to reveal the discriminatory metabolites
and identify the candidate markers of EC. A total of 41 in serum and 36
identified compounds in tissues were relevant to the malignant prognosis. A
marked metabolic reprogramming of EC was observed, including enhanced anaerobic
glycolysis and glutaminolysis, inhibited tricarboxylic acid (TCA) cycle, and
altered lipid metabolism and amino acid turnover. Based on the potential markers
of glucose, glutamic acid, lactic acid, and cholesterol, the receiver operating
characteristic (ROC) curves indicated good diagnosis and prognosis of EC. EC
patients showed distinct reprogrammed metabolism involved in glycolysis, TCA
cycle, glutaminolysis, and fatty acid metabolism. The pivotal molecules in the
metabolic pathways were suggested as the potential markers to facilitate the
early diagnosis of human EC.
PMID- 28512471
TI - Resveratrol Induces Differentiation of Human Umbilical Cord Mesenchymal Stem
Cells into Neuron-Like Cells.
AB - Objective. Human umbilical cord mesenchymal stem cells (hUC-MSCs) potentially
differentiate to various types of cells including neuron-like cells. The natural
polyphenol resveratrol benefits patients with many diseases including ischemic
brain injury. We hypothesize that resveratrol induces differentiation of hUC-MSCs
into neuron-like cells. Methods. Flow cytometry was used to determine the surface
antigens in different stage of hUC-MSCs (P2, P5, and P10). Nestin, neuron
specific enolase (NSE), and glial fibrillary acidic protein (GFAP) were detected
by immunocytochemistry, Western blotting, and real time RT-PCT. The cultured hUC
MSCs were treated with resveratrol at different concentrations (0, 7.5, 15.0, and
30.0 mg/L). Nestin, GFAP, and NSE protein and mRNA were measured at posttreatment
time points of 2 h, 4 h, 6 h, 12 h, and 24 h. Results. Neuron-like cells were
found in hUC-MSCs treated by resveratrol at concentrations of 15.0 and 30.0 mg/L,
but not in hUC-MSCs treated with vehicle and 7.5 mg/L resveratrol. Furthermore,
immunocytochemical staining revealed that nestin and NSE immunoreactivities were
positive in resveratrol-treated hUC-MSCs at concentrations of 15.0 and 30.0 mg/L.
Resveratrol treatment significantly increased nestin and NSE protein and mRNA
levels 4 h after the treatment. However, resveratrol treatment did not change
GFAP immunoreactivities and protein and mRNA expression levels in cultured hUC
MSCs. Conclusions. Taken together, resveratrol treatment induces a
differentiation of hUC-MSCs into neuron-like cells at relatively high
concentrations.
PMID- 28512472
TI - Pulsed Electromagnetic Field Regulates MicroRNA 21 Expression to Activate TGF
beta Signaling in Human Bone Marrow Stromal Cells to Enhance Osteoblast
Differentiation.
AB - Pulsed electromagnetic fields (PEMFs) have been documented to promote bone
fracture healing in nonunions and increase lumbar spinal fusion rates. However,
the molecular mechanisms by which PEMF stimulates differentiation of human bone
marrow stromal cells (hBMSCs) into osteoblasts are not well understood. In this
study the PEMF effects on hBMSCs were studied by microarray analysis. PEMF
stimulation of hBMSCs' cell numbers mainly affected genes of cell cycle
regulation, cell structure, and growth receptors or kinase pathways. In the
differentiation and mineralization stages, PEMF regulated preosteoblast gene
expression and notably, the transforming growth factor-beta (TGF-beta) signaling
pathway and microRNA 21 (miR21) were most highly regulated. PEMF stimulated
activation of Smad2 and miR21-5p expression in differentiated osteoblasts, and
TGF-beta signaling was essential for PEMF stimulation of alkaline phosphatase
mRNA expression. Smad7, an antagonist of the TGF-beta signaling pathway, was
found to be miR21-5p's putative target gene and PEMF caused a decrease in Smad7
expression. Expression of Runx2 was increased by PEMF treatment and the miR21-5p
inhibitor prevented the PEMF stimulation of Runx2 expression in differentiating
cells. Thus, PEMF could mediate its effects on bone metabolism by activation of
the TGF-beta signaling pathway and stimulation of expression of miR21-5p in
hBMSCs.
PMID- 28512474
TI - Human Papillomavirus Genotype Distribution among Cervical Cancer Patients prior
to Brazilian National HPV Immunization Program.
AB - To evaluate the impact of HPV immunization and possible changes in virus type
specific prevalence associated with cervical cancer, it is important to obtain
baseline information based on socioeconomic, educational, and environmental
characteristics in human populations. We describe these characteristics and the
type-specific HPV distribution in 1,183 women diagnosed with cervical cancer in
two Brazilian healthcare institutions located at the Southeastern (Rio de
Janeiro/RJ) and the Amazonian (Belem/PA) regions. Large differences were observed
between women in these regions regarding economic, educational, and reproductive
characteristics. The eight most frequent HPV types found in tumor samples were
the following: 16, 18, 31, 33, 35, 45, 52, and 58. Some HPV types classified as
unknown or low risk were found in tumor samples with single infections, HPV 83 in
RJ and HPV 11, 61, and 69 in PA. The proportion of squamous cervical cancer was
lower in RJ than in PA (76.3% versus 87.3%, p < 0.001). Adenocarcinoma was more
frequent in RJ than in PA (13.5% versus 6.9%, p < 0.001). The frequency of HPV 16
in PA was higher in younger women (p < 0.05). The success of a cervical cancer
control program should consider HPV types, local health system organization, and
sociodemographic diversity of Brazilian regions.
PMID- 28512475
TI - Risk Factors for Road Traffic Injuries among Different Road Users in the Gambia.
AB - We identified risk factors for road traffic injuries among road users who
received treatment at two major trauma hospitals in urban Gambia. The study
includes pedestrians, bicyclists, motorcyclists, and drivers/passengers of cars
and trucks. We examined distributions of injury by age, gender, collision vehicle
types and vehicle category, and driver and environment factors. Two hundred and
fifty-four patients were included in the study. Two-thirds were male and one
third female. Two-thirds (67%) of road traffic injuries involved pedestrians,
bicyclists, and motorcyclists; and these were more common during weekdays (74%)
than weekends. Nearly half (47%) of road traffic injuries involved pedestrians.
One-third (34%) of injured patients were students (mean age of students was less
than 14 years), more than half (51%) of whom were injured on the roadway as
pedestrians. Head/skull injuries were common. Concussion/brain injuries were 3.5
times higher among pedestrians, bicyclists, and motorcyclists than vehicle
occupants. Crashes involving pedestrians were more likely to involve young people
(<25 years; aOR 6.36, 95% CI: 3.32-12.17) and involve being struck by a motor car
(aOR 3.95, 95% CI: 2.09-7.47). Pedestrians contribute the largest proportion of
hospitalizations in the Gambia. Young pedestrians are at particularly high risk.
Prevention efforts should focus on not only vehicle and driver factors, but also
protecting pedestrians, bicyclists, and motorcyclists.
PMID- 28512476
TI - Root and Canal Morphology of Mandibular Molars in a Selected Iranian Population
Using Cone-Beam Computed Tomography.
AB - INTRODUCTION: The aim of this study was to evaluate the root canal morphology of
mandibular first and second molars using cone-beam computed tomography (CBCT) in
northern Iranian population and also to indicate the thinnest area around root
canals. METHODS AND MATERIALS: We evaluated CBCT images of 154 first molars and
147 second molars. By evaluating three axial, sagittal and coronal planes of each
tooth we determined the number of root canals, prevalence of C-shaped Melton
types, and prevalence of Vertucci configuration and inter orifice distance. Also
the minimum wall thickness of root canals was determined by measuring buccal,
lingual, distal and mesial wall thicknesses of each canal in levels with 2 mm
intervals from apex to orifice. RESULTS: Amongst 154 first mandibular molars, 149
(96.7%) had two roots, 3 (1.9%) had three roots and 2 (1.2%) had C-shaped root
configuration. Of 147 second mandibular molars, 120 (81.6%) had two roots, 1
(0.6%) had three roots and 26 (17.6%) had C-shaped roots. There was no
significant difference in the prevalence of Vertucci's type between two genders.
The most common configuration in mesial roots of first and second molars were
type IV (57%-42.9%) and type II (31.5%-28%). Mesial and distal walls had the most
frequency as the thinnest wall in all levels of root canals with mostly less than
1 mm thickness. In second molars the DB-DL inter orifice distance and in first
molars the MB-ML distance were the minimum. MB-D in first molars had the maximum
distance while ML-DL, MB-DB and ML-D had the same and maximum distance in second
molars. CONCLUSION: Vertucci's type IV and type I were the most prevalent
configurations in mesial and distal roots of first and second mandibular molars
and the thickness of thinnest area around the canals should be considered during
endodontic treatments.
PMID- 28512477
TI - Physical Properties and Chemical Characterization of Two Experimental Epoxy Resin
Root Canal Sealers.
AB - INTRODUCTION: The aim of this in vitro study was to evaluate the setting time,
flow, film thickness, solubility, radiopacity and characterization analysis of
three epoxy resin based sealers including two experimental sealers and AH-26.
METHODS AND MATERIALS: Five samples of each material were evaluated for setting
time, flow, film thickness, solubility and radiopacity according to ISO 6876
Standard. Characterization of sealers was performed under the scanning electron
microscopy (SEM), X-ray energy dispersive spectroscopy, X-ray diffraction (XRD)
and Fourier transform infrared (FTIR) spectroscopy. Statistical evaluation was
performed using the Kruskal-Wallis test. RESULTS: In this study, AH-26 showed
more radiopacity and flow compared to two other experimental sealers (P<0.05).
However, both sealers had lower setting time than AH-26 (P<0.05). No statistical
differences were found regarding film thickness, solubility and radiopacity
(P>0.05). The characterization analysis exhibited relatively similar
microstructure of AH-26 sealer to the experimental root canal sealers.
CONCLUSION: According to the result of this study, all tested root canal sealers
had acceptable properties based on ISO 6876 standard criteria.
PMID- 28512473
TI - Vitamin C in Stem Cell Biology: Impact on Extracellular Matrix Homeostasis and
Epigenetics.
AB - Transcription factors and signaling molecules are well-known regulators of stem
cell identity and behavior; however, increasing evidence indicates that
environmental cues contribute to this complex network of stimuli, acting as
crucial determinants of stem cell fate. l-Ascorbic acid (vitamin C (VitC)) has
gained growing interest for its multiple functions and mechanisms of action,
contributing to the homeostasis of normal tissues and organs as well as to tissue
regeneration. Here, we review the main functions of VitC and its effects on stem
cells, focusing on its activity as cofactor of Fe+2/alphaKG dioxygenases, which
regulate the epigenetic signatures, the redox status, and the extracellular
matrix (ECM) composition, depending on the enzymes' subcellular localization.
Acting as cofactor of collagen prolyl hydroxylases in the endoplasmic reticulum,
VitC regulates ECM/collagen homeostasis and plays a key role in the
differentiation of mesenchymal stem cells towards osteoblasts, chondrocytes, and
tendons. In the nucleus, VitC enhances the activity of DNA and histone
demethylases, improving somatic cell reprogramming and pushing embryonic stem
cell towards the naive pluripotent state. The broad spectrum of actions of VitC
highlights its relevance for stem cell biology in both physiology and disease.
PMID- 28512478
TI - Subcutaneous Reaction of Rat Tissues to Nanosilver Coated Gutta-Percha.
AB - INTRODUCTION: Gutta-percha (GP), is a neutral and non-toxic material. The aim of
this animal study was to compare the biocompatibility of nanosilver coated GP (NS
GP) with conventional GP in subcutaneous tissues in a rat model. METHODS AND
MATERIALS: Conventional GP and NS-GP were subcutaneously implanted in the backs
of 20 male Wistar rats (n=10). A control animal was assigned for each trial
period. Ten animals were sacrificed after 7 and 30 days and light microscopic
evaluation of tissue reaction to NS-GP (n=20) and conventional GP (n=20) was
accomplished. The Mann-Whitney U, Wilcoxon Signed Ranks, Fisher Exact, and
McNemar tests were used for statistical analysis of the data. RESULTS: After 7
days, inflammation was moderate and mild for NS-GP and conventional GP,
respectively (P<0.001). After 30 days, no inflammation was discernible in
conventional GP. However, mild inflammation was reported for NS-GP (P<0.001).
Regarding inflammatory cell type, there was a significant difference between two
experimental groups at both times (P<0.001). CONCLUSION: Inflammation decreased
over time in both groups. Fibrous connective tissue, a representative of healing
and control of inflammatory process, surrounded both test materials. NS-GP was
biocompatible and might be a reasonable endodontic obturation material.
PMID- 28512479
TI - In vitro Cytotoxicity Comparison of MTA Fillapex, AH-26 and Apatite Root Canal
Sealer at Different Setting Times.
AB - INTRODUCTION: This study aimed to compare the cytotoxicity of MTA Fillapex, AH-26
and Apatite root canal sealers at different times after mixing. METHODS AND
MATERIALS: In this in vitro study, MTA Fillapex, AH-26 and Apatite root canal
sealer were spilled uniformly by 40 um mesh in a 96-well plate. Then, human fetal
foreskin fibroblast cell line (HFFF2) were added to each sealer cell culture
medium. Cytotoxicity was measured using MTT assay after 24, 48 and 72 h and seven
days. Multiple comparisons were done using analysis of variances (ANOVA) and
Scheffe's post hoc test. RESULTS: All studied sealers exhibited severe
cytotoxicity (more than 70%) except for Apatite sealer (95%) at 48 h after
mixing. Cytotoxicity of MTA Fillapex and AH-26 were similar (P>0.05) at 24, 48
and 72 h and 7 days after mixing of sealers. Cytotoxicity of MTA Fillapex and
Apatite root canal sealer, at 24 and 48 h, were significantly different (P=0.003
and P=0.000, respectively); MTA Fillapex was more cytotoxic. However in 72 h and
7 days after mixing, the difference was not significant (P>0.05). At 24 and 48 h
after mixing, AH-26 was more cytotoxic (P=0.002 and P=0.000, respectively). Same
as above at 72 h and 7 days after mixing, their cytotoxicity were similar
(P>0.05). CONCLUSION: Overall cytotoxicity of all studied materials were severe.
However, it was observed that the cytotoxicity of MTA Fillapex, AH-26 and Apatite
root canal sealer decreased over time. Apatite root canal sealer exhibited the
least cytotoxicity. Cytotoxicity of MTA Fillapex and AH-26 were similar at
different time intervals.
PMID- 28512480
TI - Effect of Intra-Canal Calcium Hydroxide Remnants on the Push-Out Bond Strength of
Two Endodontic Sealers.
AB - INTRODUCTION: The aim of this study was to evaluate the effect of intra-canal
calcium hydroxide (CH) remnants after ultrasonic irrigation and hand file removal
on the push out bond strength of AH-26 and EndoSequence Bioceramic sealer (BC
Sealer). METHODS AND MATERIALS: A total of 102 single-rooted extracted human
teeth were used in this study. After root canal preparation up to 35/0.04 Mtwo
rotary file, all the specimens received CH dressing except for 34 specimens in
the control group. After 1 week, the specimens with CH were divided into 2 groups
(n=34) based on the CH removal technique; i.e. either with ultrasonic or with #35
hand file. Then specimens were divided into two subgroups according to the sealer
used for root canal obturation: AH-26 or BC Sealer. After 7 days, 1 mm-thick
disks were prepared from the middle portion of the specimens. The push out bond
strength and failure mode were evaluated. Data were analyzed by the two-way ANOVA
and Tukey's post hoc tests. RESULTS: The push out bond strength of both sealers
was lower in specimens receiving CH. These values were significantly higher when
CH was removed by ultrasonic (P<0.05). The dominant mode of failure in all
subgroups was of mixed type except for the BC Sealer specimens undergoing CH
removal with hand file which dominantly exhibited adhesive mode of failure.
CONCLUSION: CH remnants had a negative effect on the push out bond strength of AH
26 and BC Sealer. Ultrasonic irrigation was more effective in removing CH.
PMID- 28512481
TI - Influence of Root Canal Curvature on the Accuracy of Root ZX Electronic Foramen
Locator: An In Vitro Study.
AB - INTRODUCTION: The aim of this in vitro study was to evaluate the correlation
between accuracy of Root ZX electronic foramen locator and root canal curvature.
METHODS AND MATERIALS: One hundred and ten extracted mandibular molars were
selected. Access cavity was prepared and coronal enlargement of mesiobuccal canal
was performed. A #10 Flexofile was inserted into the mesiobuccal canal, and a
radiography was taken to measure the degree of curvature by Schneider's method.
The actual working length (AWL) was defined by inserting the file until its tip
could be observed at a place tangential to the major apical foramen and then 0.5
mm was subtracted from this measurement. For the electronic working length (EWL)
measurement, the apical 3 or 4 mm of the root was embedded in alginate as the
electrolyte material. The file was inserted into the root canal to the major
foramen, until the APEX reading was shown on the electronic device and then
pulled back until the visual display showed the 0.5-mm mark. The AWL was
subtracted from the EWL to define the distance between the file tip and the point
0.5 mm coronal to the major apical foramen. Data were analyzed using the
Pearson's correlation coefficient. RESULTS: The accuracy of Root ZX within +/-0.1
mm and +/-0.5 mm was 38.2% and 94.6%, respectively. There was no correlation
between the distance from the EWL to the AWL and the degree of root canal
curvature (r=0.097, P=0.317). CONCLUSION: Root canal curvature did not influence
the accuracy of Root ZX foramen locator.
PMID- 28512482
TI - Effect of Field Of View on Detection of External Root Resorption in Cone-Beam
Computed Tomography.
AB - INTRODUCTION: Conventional methods for diagnosis of external root resorption
(ERR) are based on clinical findings and x-ray observations which are not
appropriate for early diagnosis. The present study assessed the effect of
different sizes and field of views (FOVs) in the diagnosis of simulated external
root resorption by cone-beam computed tomography (CBCT). METHODS AND MATERIALS:
In this diagnostic in vitro trial, 100 human extracted mandibular central
incisors were collected and marked in 3 apical, middle and coronal areas.
Cavities with different sizes were created in buccal and lingual surfaces of each
area. Following this procedure, CBCT images were taken in 2 different 6 * 6 cm
and 12 * 8 cm FOVs with the same voxel size of 0.2 mm. Absence or presence of
cavities in CBCT images were assigned by 3 radiologists and compared with gold
standard results which were obtained by measurement of the size of cavities using
a digital caliper. Sensitivity and specificity values, positive predictive value
(PPV) and negative predictive value (NPV), AZ value and Kappa values were
calculated and reported. RESULTS: Amounts of sensitivity in 6 * 6 cm FOV with
voxel size of 0.2 mm for small, medium and large cavities were 95.93%, 96.03% and
97.1%, respectively. Amounts of sensitivity in 12 * 8cm FOV with the same voxel
size for small, medium and large cavities were noted as 94.4%, 96.03% and 98.5%,
respectively. However, specificity in FOV of 6 * 6 cm and FOV of 12 * 8 cm was
calculated as 93.03% and 90.83%, respectively. CONCLUSION: Both used FOVs show
nearly same performances in the case of detection of ERR; therefore, smaller FOV
should be preferably used for detection of ERR in order to decrease the amount of
imposed radiation dose given to patients.
PMID- 28512483
TI - Efficacy of Different Root Canal Irrigants on Smear Layer Removal after Post
Space Preparation: A Scanning Electron Microscopy Evaluation.
AB - INTRODUCTION: Effective durable adhesion between post material and dentine using
resin cements is essential for longevity of restoration. The aim of this in vitro
study was to compare the effect of different irrigants on smear layer removal
after post space preparation. METHODS AND MATERIALS: A total of 75 extracted
anterior human teeth were selected. The canals were instrumented by rotary system
and then were filled. After preparing the post space, teeth were divided into 5
groups according to irrigants: 17% EDTA; 17% EDTA+2% CHX; 5.25% NaOCl; 17%
EDTA+5.25% NaOCl; and saline. The canals were irrigated with 5 cc of each
irrigants for 1 min. Specimens were examined with scanning electron microscopy
(SEM). Hulsmann's score was used for marking of smear layer removal at coronal,
middle and apical thirds of post space. The data were analyzed using the Kruskal
Wallis and Mann-Whitney U tests. RESULTS: The results revealed that subsequent
use of 17% EDTA+5.25% NaOCl was more effective than the other groups in smear
layer removal. No statistical difference was found among different levels of root
canal within each group. CONCLUSION: It can be concluded that 17% EDTA+5.25%
NaOCl could be an effective irrigant for smear layer removal after post space
preparation.
PMID- 28512484
TI - Scanning Electron Microscopy and Energy-Dispersive X-Ray Microanalysis of Set CEM
Cement after Application of Different Bleaching Agents.
AB - INTRODUCTION: The present study evaluated the element distribution in completely
set calcium-enriched mixture (CEM) cement after application of 35% carbamide
peroxide, 40% hydrogen peroxide and sodium perborate as commercial bleaching
agents using an energy-dispersive x-ray microanalysis (EDX) system. The surface
structure was also observed using the scanning electron microscope (SEM). METHODS
AND MATERIALS: Twenty completely set CEM cement samples, measuring 4*4 mm2, were
prepared in the present in vitro study and randomly divided into 4 groups based
on the preparation technique as follows: the control group; 35% carbamide
peroxide group in contact for 30-60 min for 4 times; 40% hydrogen peroxide group
with contact time of 15-20 min for 3 times; and sodium perborate group, where the
powder and liquid were mixed and placed on CEM cement surface 4 times. Data were
analyzed at a significance level of 0.05 through the one Way ANOVA and Tukey's
post hoc tests. RESULTS: EDX showed similar element distribution of oxygen,
sodium, calcium and carbon in CEM cement with the use of carbamide peroxide and
hydroxide peroxide; however, the distribution of silicon was different (P<0.05).
In addition, these bleaching agents resulted in significantly higher levels of
oxygen and carbon (P<0.05) and a lower level of calcium (P<0.05) compared to the
control group. SEM of the control group showed plate-like and globular structure.
Sodium perborate was similar to control group due to its weak oxidizing
properties. Globular structures and numerous woodpecker holes were observed on
the even surface on the carbamide peroxide group. CONCLUSION: The mean elemental
distribution of completely set CEM cement was different when exposed to sodium
perborate, carbamide peroxide and hydrogen peroxide.
PMID- 28512485
TI - Effect of Blood Exposure on Push-Out Bond Strength of Four Calcium Silicate Based
Cements.
AB - INTRODUCTION: The purpose of this study was to compare the push-out bond strength
of white ProRoot Mineral Trioxide Aggregate (MTA), Biodentine, calcium-enriched
mixture (CEM) cement and Endosequence Root Repair Material (ERRM) putty after
exposure to blood. METHODS AND MATERIALS: A total of 96 root dentin slices with a
standardized thickness of 1.00+/-0.05 mm and standardized canal spaces were
randomly divided into 4 main experimental groups (n=24) according to the calcium
silicate based cement (CSC) used: white ProRoot MTA, CEM Cement, ERRM Putty and
Biodentine. Specimens were exposed to whole fresh human blood and then subdivided
into two subgroups depending on the exposure time (24 or 72 h). Push-out bond
strength was measured using a universal testing machine. Failure modes were
examined under a light microscope under *10 magnification. Data were analyzed
using the two-way ANOVA test. RESULTS: Biodentine exhibited the highest values
regardless of the exposure time. The lowest push-out strength values were seen in
white ProRoot MTA and CEM cement in both post exposure times. After exposure to
blood, the push-out bond strength of all materials increased over time. This
increase was only statistically significant in white ProRoot MTA and ERRM
specimens. The dominant failure mode in all CSCs was the adhesive mode.
CONCLUSION: Biodentine showed the highest values of push-out bond strength and
may be better options for situations encountering higher dislocation forces in a
short time after cement application.
PMID- 28512487
TI - Comparative Antimicrobial Efficacy of Eucalyptus Galbie and Myrtus Communis L.
Extracts, Chlorhexidine and Sodium Hypochlorite against Enterococcus Faecalis.
AB - INTRODUCTION: The aim of this study was to evaluate the antimicrobial effect of
Eucalyptusgalbie and Myrtus communis L. methanolic extracts, chlorhexidine (CHX)
and sodium hypochlorite (NaOCl) on Enterococcus faecalis (E. faecalis) as the
predominant species isolated from infected root canals. METHODS AND MATERIALS:
One hundred twenty mandibular premolars were randomly divided into 8 groups:
Eucalyptusgalbie (E. galbie) 12.5 mg/mL, Myrtus communis L. (M. communis L.) 6.25
mg/mL, 0.2% CHX, %2 CHX, 2.5% NaOCl, 5.25% NaOCl, positive and negative control
group. Sampling was performed using paper points (from the root canal space
lumen) and Gates-Glidden drills (from the dentinal tubules); then colony forming
units (CFU) were counted and analyzed using the Kruskal-Wallis test, followed by
Mann Whitney U test. The level of significance was set at 0.05. RESULTS: All
irrigants reduced more than 99% of bacteria in root canal. In the presence of M.
communis L. and E. galbie, the bacterial count in dentin were significantly more
than CHX and NaOCl groups (P<0.05) except 0.2% CHX in 200 um and 400 um depths
(P>0.05). CONCLUSION: Although 5.25% NaOCl was the most effective irrigant, all
agents exerted acceptable antimicrobial activity against E. faecalis.
PMID- 28512486
TI - Students' Knowledge Comprehension after Implementation of Live Conventional
Demonstration, Video Teaching and Video-Assisted Instruction Methods in
Endodontic Practice.
AB - INTRODUCTION: Video-assisted clinical instruction (VACID) has been found to be a
beneficial teaching tool for various fields in dentistry. The aim of this
interventional study was to compare the efficacy of live conventional
demonstration (CD), video teaching, and VACID (video with explanation) methods in
teaching of root canal treatment to undergraduate dental students. METHODS AND
MATERIALS: Forty-two undergraduate senior dental students participated in this
study. The students experienced this course for the first time and were randomly
divided into three groups (n=14). Group A attended live CD on a patient; group B
watched a professionally produced demonstration video without any verbal
explanation during 1 h; and finally group C watched the same video alongside live
explanation by a mentor during the 1.5 h (VACID). The whole process was performed
by an experienced endodontist on maxillary central incisors. All of The students
carried out a multiple choice question exam to evaluate their comprehension. The
mean score of the experimental groups were compared using ANOVA test and multiple
comparisons were carried out with Tamhane test. The level of significance was set
at 0.05. RESULTS: There was significant difference among three groups according
to the ANOVA test (P<0.05). Group VACID had the highest mean scores. There was
significant difference between the groups VACID and VT (P=0.011); no significant
differences were found in other inter-group comparisons. CONCLUSION: According to
the results, VACID may improve the quality of endodontic training in
undergraduate dental students.
PMID- 28512488
TI - In Vitro Microleakage of Mineral Trioxide Aggregate, Calcium-Enriched Mixture
Cement and Biodentine Intra-Orifice Barriers.
AB - INTRODUCTION: This in vitro study compared the coronal microleakage of mineral
trioxide aggregate (MTA), calcium-enriched mixture (CEM) cement and Biodentine as
intra-orifice barriers. METHODS AND MATERIALS: The study was conducted on 76
extracted single-canal human teeth. Their root canals were prepared using
ProTaper rotary files and filled with gutta percha and AH-26 sealer using lateral
condensation technique. Coronal 3 mm of the gutta percha was removed from the
root canals and replaced randomly with MTA, CEM cement or Biodentine in the three
experimental groups (n=22). A positive and a negative control group were also
included (n=5). The entire root surfaces of all teeth were covered with two
layers of nail varnish in such a way that only the access openings were not
coated. In the negative control group, the access opening was also coated with
nail varnish. All teeth were immersed in India ink and after clearing, the
samples were evaluated under a stereomicroscope under *10 magnification to assess
the degree of dye penetration. The data were analyzed using the Kruskal-Wallis
test. The level of significance was set at 0.05. RESULTS: The negative control
group showed no leakage while the positive control group showed significantly
higher microleakage than the test groups (P>0.05). CEM cement had the lowest
(0.175+/-0.068 mm) and MTA showed the highest dye penetration (0.238+/-0.159 mm)
among the experimental groups; although these differences were not statistically
significant (P=0.313). CONCLUSION: CEM cement exhibited the least microleakage as
an intra-orifice barrier in endodontically treated teeth.
PMID- 28512489
TI - Effect of Deep Cryogenic Treatment on Cyclic Fatigue of Endodontic Rotary Nickel
Titanium Instruments.
AB - INTRODUCTION: Cyclic fatigue is the common reason for breakage of rotary
instruments. This study was conducted to evaluate the effect of cryogenic
treatment (CT) in improving the resistance to cyclic fatigue of endodontic rotary
instruments. METHODS AND MATERIALS: In this in vitro study, 20 RaCe and 20 Mtwo
files were randomly divided into two groups of negative control and CT. CT files
were stored in liquid nitrogen at -196 degrees C for 24 h, and then were
gradually warmed to the room temperature. All files were used (at torques and
speeds recommended by their manufacturers) in a simulated canal with a 45 degrees
curvature until breakage. The time to fail (TF) was recorded and used to
calculate the number of cycle to fail (NCF). Groups were compared using
independent-samples t-test. RESULTS: Mean NCFs were 1248.2+/-68.1, 1281.6+/-78.6,
4126.0+/-179.2, and 4175.4+/-190.1 cycles, for the Mtwo-control, Mtwo-CT, RaCe
control, and RaCe-CT, respectively. The difference between the controls and their
respective CT groups were not significant (P>0.3). The difference between the
systems was significant. CONCLUSION: Deep CT did not improve resistance to cyclic
fatigue of the evaluated rotary files.
PMID- 28512490
TI - In Vitro Cytotoxicity of a New Nano Root Canal Sealer on Human Gingival
Fibroblasts.
AB - INTRODUCTION: The aim of this in vitro study was to evaluate the cytotoxicity of
a new nano zinc-oxide eugenol (NZOE) sealer on human gingival fibroblasts (HGFs)
compared with Pulpdent (micro-sized ZOE sealer) and AH-26 (resin-based sealer).
METHODS AND MATERIALS: The Pulpdent, AH-26, and NZOE sealers were prepared and
exposed to cell culture media immediately after setting, and 24 h and one week
after setting. Then, the primary cultured HGFs were incubated for 24 h with
different dilutions (1:1 to 1:32) of each sealer extract. Cell viability was
evaluated by methyl thiazolyl diphenyl tetrazolium bromide (MTT) assay. The
results were compared using two-way analysis of variance followed by Tukey's post
hoc test. The level of significance was set at 0.05. RESULTS: All sealer
extracts, up to 32 times dilutions, showed cytotoxicity when exposed to HGF
immediately after setting. The extracts obtained 24 h or one week after setting
showed lower cytotoxicity than extracts obtained immediately after setting. At
all setting times, NZOE showed lower cytotoxicity than Pulpdent and AH-26. While
one-week extracts of NZOE had no significant effect on the viability of HGF at
dilutions 1:4 to 1:32, both Pulpdent and AH-26 decreased the cell viability at
dilutions of 1:4 and 1:8. CONCLUSION: NZOE exhibited lower cytotoxicity compared
to Pulpdent and AH-26 on HGF and has the potential to be considered as a new root
canal filling material.
PMID- 28512491
TI - Pulp Response following Direct Pulp Capping with Dentin Adhesives and Mineral
Trioxide Aggregate; An Animal Study.
AB - INTRODUCTION: Pulp vitality and its continuous dentin prodution are essential for
long-term success of direct pulp capping (DPC). The aim of present study was to
evaluate the histopathological response of the canine pulp following DPC using
either different dentin adhesive resins (DAR), calcium hydroxide (CH) or mineral
trioxide aggregate (MTA). METHODS AND MATERIALS: DPC was done on 72 dog's teeth
using 6 types of dental materials (n=12) (4 types of DAR, white MTA and CH).
Therefore, six healthy dogs were anesthetized and 2 teeth from each dog were
allocated to either type of mentioned DPC agents. The dental pulps were exposed
mechanically by drilling in the center of class V cavities. The different types
of capping materials included DARS (Clearfil S3 Bond, Optibond FL, Single Bond
and Clearfil SE Bond), white MTA and CH. After 7, 21 and 63 days, two dogs were
euthanized in each interval. Microscopic evaluations were done according to
following criteria: intensity of inflammation, presence of necrosis and formation
of hard tissue. The recorded data were analyzed by the Kruskal-Wallis, Friedman,
Cochran's and Fisher's exact tests using SPSS software version 12 at significant
level of 0.05. RESULTS: No significant differences were found regarding necrosis
among DPC materials (P>0.05). However, MTA caused higher amount of hard tissue
formation after 63 days in comparison with 21 days. CONCLUSION: MTA provided the
highest degree of hard tissue formation after 63 days. However, further studies
should be performed for administering a definitive material.
PMID- 28512492
TI - In Vitro Sealing Properties of Calcium-Enriched Mixture and Mineral Trioxide
Aggregate Orifice Barriers during Intra-Coronal Bleaching.
AB - INTRODUCTION: This study aimed at evaluating the sealing properties of calcium
enriched mixture (CEM) compared to mineral trioxide aggregate (MTA) as a cervical
barriers in intra-coronal bleaching. METHODS AND MATERIALS: In this in vitro
study, endodontic treatment was performed on 60 extracted human incisors and
canines without canal calcification, caries, restorations, resorption or cracks.
The teeth were then randomly divided into two experimental groups and two control
groups (n=15). Then, CEM cement and MTA were applied as 3-mm intra-orifice
barriers in the test groups; a mixture of sodium perborate and 30% hydrogen
peroxide bleaching agents were placed within the pulp chamber for one week. Dye
penetration method was used to evaluate the sealing ability of agents.
Statistical analysis was performed using SPSS software. The Kendall coefficient
was used to evaluate inter-observer agreement. The chi-squared test was used for
statistical analysis. RESULTS: The results showed that the penetration rates of
CEM and MTA were the same as positive control group, with no significant
differences (P=0.673 and P=0.408, respectively). However, there was a significant
difference between the negative control group and CEM and MTA groups (P=0.001 for
both groups). In addition, the sealing ability of MTA and CEM cement were not
significantly different (P=0.682). CONCLUSION: During intra-coronal bleaching
procedures CEM cement can be used as a cervical barrier with sealing properties
comparable to that of MTA.
PMID- 28512493
TI - Radiographic Quality of Root Canal Obturation Performed By Fifth Year Students of
Hamadan Dental School.
AB - INTRODUCTION: The aim of this study was to assess the radiographic technical
quality of root canal therapy performed by fifth year students of Dental School
of Hamadan University of Medical Sciences from 2015 to 2016. METHODS AND
MATERIALS: Four hundred and seventy records of root canal therapies were
evaluated. Records with graphies taken as initial, master apical file (MAF),
master apical cone (MAC) and final radiographs were included in the study and
records of patient younger than 16 years and older than 68 years were excluded
from further investigations. Lastly, 432 teeth were selected. Obturation length,
canal tapering, quality and density of filling material were the variables
investigated in the present study. Two independent investigators examined the
radiographies using a magnifying lens (*2) and x-ray viewer. Data were analyzed
using chi-square test. RESULTS: The technical quality of root filling performed
by undergraduate dental students was classified as acceptable in 10.4% of cases.
Moreover, 70.8% of teeth had adequate filling, 17.1% were underfilled and 12%
were overfilled. The three groups were significantly different in terms of
working length and taper quality. One hundred ninety four (44.9%) records had
adequate taper and 109 (25%) records had adequate density. There was a
significant association between teeth location and the length of obturation so
that the probability of a successful treatment was higher in maxillary teeth.
Furthermore, the rate of a proper length of obturation was higher among incisors
than that of premolars and molars. CONCLUSION: The technical quality of root
canal therapy performed by dental students in Hamadan University of medical
sciences is not as acceptable as it should be. One of the most important factors
in this regard is a high student/professor ratio.
PMID- 28512494
TI - Cleanliness of Canal Walls following Gutta-Percha Removal with Hand Files, RaCe
and RaCe plus XP-Endo Finisher Instruments: A Photographic in Vitro Analysis.
AB - INTRODUCTION: Gutta-percha must be removed from the root canal space during
retreatment to ensure a more favorable outcome. The aim of this study was to
compare the efficacy of hand instruments, RaCe and RaCe plus XP-endo finisher
instruments in removal of gutta-percha from root canal walls during retreatment.
METHODS AND MATERIALS: Thirty single-rooted premolars were prepared, obturated,
and divided into three groups according to retreatment method; in group 1,
retreatment was carried out by hand instruments, while in groups 2 and 3
retreatment was done using RaCe rotary files alone or accompanied by XP-endo
finisher instruments, respectively. After retreatment, teeth were sectioned
longitudinally and photographic images were taken. The amount of remaining gutta
percha in coronal, middle and apical thirds was quantified using Image J
software. The two-way ANOVA and post hoc Tukey's tests were used to analyze data.
The level of significance was set at 0.05. RESULTS: RaCe cleaned the apical third
significantly better than hand instrumentation. In the coronal third, RaCe+XP
endo finisher was more effective than RaCe. RaCe+XP-endo finisher was more
effective than hand instrumentation in the entire root canal. The amount of
remaining gutta-percha was the least in the apical part and increased toward the
coronal part with the use of XP-endo finisher (P<0.05). CONCLUSION: Rotary
instrumentation was more effective in removing gutta-percha from the canal walls.
Furthermore, use of XP-endo finisher file resulted in cleaner canal walls and was
more effective in removing gutta-percha from the coronal toward the apical part
of the canal.
PMID- 28512495
TI - Endodontic Management of Open Apex Teeth Using Lyophilized Collagen Sponge and
MTA Cement: Report of Two Cases.
AB - Teeth with open apices, such as in immature teeth or those with apical root
resorption are clinical cases with difficult immediate resolution. With the use
of mineral trioxide aggregate (MTA) in dentistry, it was possible to optimize the
treatment time of these cases by immediate placement of apical plug and the root
canal filling. However, some negative effects can occur if MTA is extruded beyond
the apex. To avoid this accident, it has been recommended to use of an apical
matrix prior to placement of MTA. This study reports two clinical cases of apical
plug placement in teeth with pulp necrosis and open apices. One case had an
immature apex due to dental trauma and the other case had apical resorption due
to the presence of endodontic infection in the root canal. MTA apical plug with
approximately 4 mm thickness, was placed in the apical zone of the root and
immediately the canal was obturated with gutta-percha and endodontic sealer.
Follow-up evaluations showed clinical and radiographic evidence of success.
PMID- 28512496
TI - Nonsurgical Management of a Large Periapical Lesion: A Case Report.
AB - This case report describes the non-surgical management of a large cyst-like
periapical lesion in the mandible of a 16-year-old female with the chief
complaint of periodic swelling and pus drainage from the mandibular anterior
region gingivae with no history of pain and traumatic accident in this area. Both
mandibular central incisors had extensive caries. Root canals of both mandibular
central incisors were filled with calcium hydroxide. After 10 days, endodontic
therapy was carried out on both teeth. Clinical and radiographic re-evaluations
at 3 and 12 months revealed progressing bone healing. This case report shows that
appropriate diagnosis in combination with root canal treatment as a conservative
non-surgical approach can lead to complete healing of large lesions without
invasive treatments.
PMID- 28512497
TI - Management of Perforating Idiopathic Internal Root Resorption.
AB - This case report describes the endodontic treatment of an idiopathic perforated
internal root resorption. A 24-year-old male Malay patient presented with
internal root resorption of two of his anterior teeth. The medical history was
non-contributory and he had no history of traumatic injury or orthodontic
treatment. Cone-beam computed tomography (CBCT) determined the nature, location
and severity of the resorptive lesion. Non-surgical root canal treatment of tooth
#22 and combined non-surgical and surgical approach for tooth #11 were carried
out using mineral trioxide aggregate (MTA) as the filling material. The clinical
and radiographic examination three years after completion of treatment revealed
evidences of periapical healing. The appropriate diagnosis and the treatment of
internal root resorption allowed good healing of these lesions and maintained the
tooth in function for as long as possible.
PMID- 28512499
TI - Neuroprotective Effect of Fagopyrum dibotrys Extract against Alzheimer's Disease.
AB - Accumulated evidence suggests that polyphenolic antioxidants present in herbs
play important roles in prevention of AD; the molecular mechanisms behind
neuroprotective actions rely on the phenols through different effects on the
amyloid-aggregation pathway. Fagopyrum dibotrys is a traditional herbal medicine
which contains high quantity phenols. In present study, we investigate the
beneficial pharmacological actions of Fagopyrum dibotrys extract in the APP/PS1
transgenic mouse mode; meanwhile, effects of the FDE on the fibrillation and
cytotoxicity of Abeta peptide were evaluated in vitro. After 9-month treatment,
FDE exhibited multifunctional properties on Abeta-related pathologies, which
cleaned Abeta deposits in the brain and decreased Abeta burden in the plasma,
inhibited microhaemorrhage, and reduced reactive microglia in APP/PS1 transgenic
mice and also promoted Abeta fibrils disaggregation and inhibited neurotoxicity
induced by Abeta in SH-SY5Y cells. These results highlighted that FDE is an AD
type pathology modulator with therapeutic potential against AD.
PMID- 28512498
TI - Treatment Outcomes of Full Pulpotomy as an Alternative to Tooth Extraction in
Molars with Hyperplastic/Irreversible Pulpitis: A Case Report.
AB - Root canal therapy (RCT) is a common and successful treatment for irreversible
pulpitis due to carious pulp exposure in mature permanent teeth. However, it is
often an expensive procedure, may require multiple appointments, and requires a
high level of training and clinical skill, specifically in molars. Uninsured
patients, low-income patients, and patients with limited access to specialist
care often elect for extraction of restorable teeth with irreversible pulpitis.
There is a need for an alternative affordable treatment option to preserve their
teeth and maintain chewing function. A case of pulpotomy using calcium-enriched
mixture (CEM) cement in two maxillary molars (#14 and 15) in a healthy 36-year
old patient is presented. Both teeth were diagnosed with symptomatic
hyperplastic/irreversible pulpitis. Patient did not have dental insurance, was
unable to afford RCT, and refused to extract the teeth. CEM pulpotomy and amalgam
build-ups were done as an alternative to extraction. At 2-year recall, both teeth
were functional with no signs/symptoms of inflammation/infection. Periapical
radiographs and 3D images showed normal PDL around all roots. Pulpotomy with CEM
biomaterial might be a viable alternative to tooth extraction for mature
permanent teeth with hyperplastic/irreversible pulpitis, and can result in long
term tooth retention and improved oral health.
PMID- 28512501
TI - Effect of Traditional Chinese Medicine Product, QiangGuYin, on Bone Mineral
Density and Bone Turnover in Chinese Postmenopausal Osteoporosis.
AB - Introduction. The aim of this study was to investigate the efficacy of herbal
formula QiangGuYin (QGY) in postmenopausal women. Materials and Methods. A total
of 240 participants from six clinical centers were randomly to receive
alendronate 70 mg/week, QGY granules 20 g/day, and placebo. Primary end points
were BMD changes over 6 and 12 months; secondary end points were bone turnover
markers changes at 3, 6, 9, and 12 months. Safety was monitored by clinical
adverse events reported during the follow-up. Results. Of 240 women recruited,
218 completed the study. Significant BMD increases from baseline were observed
over 6 and 12 months at each observed part both in QGY and alendronate compared
with placebo (p < 0.01). Alendronate-treated subjects had significant decreases
in beta-CTX compared to QGY-treated subjects at each time point assessed (p <
0.01). Reduction in t-P1NP was only observed in the QGY group at 3 and 6 months (
23.81% and -3.07%, resp.). No significant difference was observed in the overall
incidence of clinical adverse events among the alendronate group and the QGY
group (5.0% versus 7.5%, p = 0.513). Conclusion. 1-Year treatment with QGY
demonstrated a safe statistical increase in BMD and new balance may be rebuilt
after 9 months. This trail is registered with ChiCTR-POC-16008026.
PMID- 28512500
TI - The Effect of Chunghyul-Dan on Hyperventilation-Induced Carbon Dioxide Reactivity
of the Middle Cerebral Artery in Normal Subjects: A Dose-Dependent Study.
AB - Background. This study was conducted to show the prompt effect of chunghyul-dan
(CHD) on cerebral hemodynamics in order to provide evidence for its use in stroke
prevention. Methods. Hyperventilation-induced CO2 reactivity of the middle
cerebral artery was measured in 12 healthy male volunteers (mean age: 26.3 +/-
1.1 years) using transcranial Doppler sonography. All subjects were examined
before and for 3 hours after administration, with an interval of 1 week between
measurements. Results. Compared to baseline, the CO2 reactivity of the middle
cerebral artery increased significantly at 2 and 3 hours after the administration
of CHD (600 mg and 1200 mg). The mean blood pressure and heart rate did not vary
from the baseline values in all groups. Conclusion. These data suggest that CHD
administration (especially 600 mg) immediately improves cerebral blood flow.
PMID- 28512503
TI - Massive Oculomotor Nerve Enlargement: A Case of Presumed Schwannomatosis.
AB - A 45-year-old man presented with a slowly progressive pupil-involving third nerve
palsy. Magnetic resonance imaging (MRI) revealed a tubular lesion extending from
the interpeduncular cistern through the cavernous sinus and into the left orbit
where it branched into a superior and an inferior division, clearly outlining the
anatomy of the third cranial nerve. Multiple other, less pronounced, enlarged
cranial nerves were noted. The differential diagnosis included chronic
inflammatory demyelinating polyneuropathy (CIDP), hereditary motor and sensory
neuropathy (HMSN), neurofibromatosis (NF), and schwannomatosis. The absence of
other muscle weakness and of sensory symptoms combined with normal peripheral
nerve conduction studies effectively ruled out the hypertrophic polyneuropathies
and pointed to a syndromic cause of multiple benign peripheral nerve sheath
tumours (PNSTs). The authors are treating this case as presumed schwannomatosis,
a syndrome similar to NF2 with much lower frequency of acoustic neuromas.
PMID- 28512502
TI - Health Inequalities Associated with Post-Stroke Visual Impairment in the United
Kingdom and Ireland: A Systematic Review.
AB - The aim of this study was to report on the health inequalities facing stroke
survivors with visual impairments as described in the current literature. A
systemic review of the literature was conducted to investigate the potential
health inequalities facing stroke survivors with subsequent visual impairments. A
quality-of-evidence and risk-of-bias assessment was conducted for each of the
included articles using the appropriate tool dependent on the type of article.
Only four articles discussed health inequalities affecting stroke survivors with
visual impairment specifically. A further 23 articles identified health
inequalities after stroke, and 38 reported on health inequalities within the
visually impaired UK or Irish population. Stroke survivors with visual impairment
face inconsistency in eye care provision nationally, along with variability in
the assessment and management of visual disorders. The subgroups identified as
most at risk were females; black ethnicity; lower socioeconomic status; older
age; and those with lower education attainment. The issue of inconsistent service
provision for this population must be addressed in future research. Further
research must be conducted in order to firmly establish whether or not stroke
survivors are at risk of the aforementioned sociodemographic and economic
inequalities.
PMID- 28512504
TI - A Case Report of Drug-Induced Myopathy Involving Extraocular Muscles after
Combination Therapy with Tremelimumab and Durvalumab for Non-Small Cell Lung
Cancer.
AB - Recently developed anti-tumour therapies targeting immune checkpoints include
tremelimumab and durvalumab. These agents have incompletely characterised side
effect profiles. The authors report a 68-year-old man treated for non-small cell
lung cancer (NSCLC) with a combination of tremelimumab and durvalumab. After
treatment he developed diplopia, ptosis, fatigue, weakness, and an inflammatory
myopathy affecting the extraocular muscles requiring hospitalisation.
Electromyography (EMG) testing and muscle biopsy suggested inflammatory myopathy
without sign of myasthenia. Within 1 month of withdrawal of cancer therapies and
initiation of oral steroid therapy, ocular and systemic symptoms had resolved.
This notable adverse effect has not been previously described for these drugs
administered singly or in combination, and ophthalmologists should be aware of
this presentation in patients treated with these agents.
PMID- 28512505
TI - Chronic Invasive Fungal Sinusitis Presenting as Inferior Altitudinal Visual Field
Defect.
AB - A young male with acute blurring of vision (6/9) complained of an inferior
altitudinal field defect in right eye. Clinical ophthalmological examination was
normal. Magnetic resonance imaging (MRI) of the brain revealed the expansion and
mucosal thickening of right posterior ethmoid and sphenoid sinuses and opacified
right maxillary sinus. Surgical intervention (transethmoidal sphenoidotomy) and
histopathological examination revealed chronic invasive granulomatous fungal
sinusitis. Anti-fungal therapy led to resolution of visual complaints and
restoration of visual field defects.
PMID- 28512506
TI - Case of Primary Leptomeningeal Lymphoma Presenting with Papilloedema and
Characteristics of Pseudotumor Syndrome.
AB - The authors describe an immunocompetent, 50-year-old man who complained of a
daily transient blurring of his vision with bilateral papilloedema. His visual
acuity was 20/20 OU, and the blind spot was enlarged bilaterally. There was
intracranial hypertension, but imaging for systemic and brain tumours were
negative. These findings suggested a diagnosis of the pseudotumor syndrome.
However, MRI showed leptomeningeal enhancement, and acetazolamide successfully
resolved his visual symptoms and papilloedema. Cytology and flow cytometry of the
CSF led to the final diagnosis of primary leptomeningeal lymphoma (PLML).
Clinicians need to be aware that a case of PLML may be misdiagnosed as peudotumor
cerebri.
PMID- 28512507
TI - Homonymous Hemianopsia Due to Posterior Cortical Atrophy.
AB - A 63-year-old woman presented to her ophthalmologist complaining of reading
difficulties for two years. Ophthalmological examination revealed a homonymous
hemianopsia. Brain magnetic resonance imaging (MRI) scan was interpreted as
normal, but positron emission tomography (PET) showed areas of posterior brain
hypometabolism. This case highlights the high diagnostic suspicion that
ophthalmologists should have regarding posterior cortical atrophy (including the
visual variant of Alzheimer disease) in patients complaining of reading
difficulties in the setting of a normal ophthalmic examination.
PMID- 28512508
TI - Lhermitte-Duclos Disease and Cerebellar Gangliocytoma-An Incidental Finding in a
Patient with Gradual Vision Loss.
AB - A 50-year-old male patient presented to the neuro-ophthalmology clinic with chief
complaints of gradual decrease in vision in both eyes, more in the left eye, for
6 years. On general examination, the patient had a hemiplegic gait. His
presenting acuity was 20/50 in the right eye and 20/320 in the left eye, not
improving further. He had dense posterior subcapsular cataracts in both eyes, and
fundus examination revealed pale discs. Humphrey visual field tests 30-2 revealed
a vertical nasal midline defect in the right eye and grossly depressed fields in
the left eye. Keeping in mind the above findings, the authors requested for a
magnetic resonance imaging (MRI) of the brain. The brain MRI shows a large
infarct in the right parieto-occipital lobe and a small circumscribed lesion in
the left cerebellum. The radiologist opined that it could possibly be a
gangliocytoma of the cerebellum, and a possible diagnosis of Lhermitte-Duclos
syndrome was made.
PMID- 28512510
TI - Unilateral Ptosis and Homolateral Hemifacial Weakness in Chronic Progressive
External Ophthalmoplegia.
PMID- 28512509
TI - United Kingdom CSF Disorders Day, 14th October 2016, University Hospitals
Birmingham.
AB - The management of patients with cerebrospinal fluid (CSF) disorders requires a
multi-specialty approach involving specialists in neurosurgery, neurology,
neuroradiology, and neuro-ophthalmology. A symposium on CSF disorders took place
at University Hospitals Birmingham and covered a selection of the more
challenging and controversial issues facing the multi-specialty team. The meeting
also featured a synopsis of the latest scientific research. The authors provide
an overview of the event.
PMID- 28512511
TI - Automated Detection of Red Lesions Using Superpixel Multichannel Multifeature.
AB - Red lesions can be regarded as one of the earliest lesions in diabetic
retinopathy (DR) and automatic detection of red lesions plays a critical role in
diabetic retinopathy diagnosis. In this paper, a novel superpixel Multichannel
Multifeature (MCMF) classification approach is proposed for red lesion detection.
In this paper, firstly, a new candidate extraction method based on superpixel is
proposed. Then, these candidates are characterized by multichannel features, as
well as the contextual feature. Next, FDA classifier is introduced to classify
the red lesions among the candidates. Finally, a postprocessing technique based
on multiscale blood vessels detection is modified for removing nonlesions
appearing as red. Experiments on publicly available DiaretDB1 database are
conducted to verify the effectiveness of our proposed method.
PMID- 28512512
TI - Learning about Chemiosmosis and ATP Synthesis with Animations Outside of the
Classroom.
AB - Many undergraduate biology courses have begun to implement instructional
strategies aimed at increasing student interaction with course material outside
of the classroom. Two examples of such practices are introducing students to
concepts as preparation prior to instruction, and as conceptual reinforcement
after the instructional period. Using a three-group design, we investigate the
impact of an animation developed as part of the Virtual Cell Animation Collection
on the topic of concentration gradients and their role in the actions of ATP
synthase as a means of pre-class preparation or post-class reinforcement compared
with a no-intervention control group. Results from seven sections of introductory
biology (n = 732) randomized to treatments over two semesters show that students
who viewed animation as preparation (d = 0.44, p < 0.001) or as reinforcement (d
= 0.53, p < 0.001) both outperformed students in the control group on a follow-up
assessment. Direct comparison of the preparation and reinforcement treatments
shows no significant difference in student outcomes between the two treatment
groups (p = 0.87). Results suggest that while student interaction with animations
on the topic of concentration gradients outside of the classroom may lead to
greater learning outcomes than the control group, in the traditional lecture
based course the timing of such interactions may not be as important.
PMID- 28512513
TI - Using a Concept Inventory to Reveal Student Thinking Associated with Common
Misconceptions about Antibiotic Resistance.
AB - Misconceptions, also known as alternate conceptions, about key concepts often
hinder the ability of students to learn new knowledge. Concept inventories (CIs)
are designed to assess students' understanding of key concepts, especially those
prone to misconceptions. Two-tiered CIs include prompts that ask students to
explain the logic behind their answer choice. Such two-tiered CIs afford an
opportunity for faculty to explore the student thinking behind the common
misconceptions represented by their choice of a distractor. In this study, we
specifically sought to probe the misconceptions that students hold prior to
beginning an introductory microbiology course (i.e., preconceptions). Faculty
learning communities at two research-intensive universities used the validated
Host-Pathogen Interaction Concept Inventory (HPI-CI) to reveal student
preconceptions. Our method of deep analysis involved communal review and
discussion of students' explanations for their CI answer choice. This approach
provided insight valuable for curriculum development. Here the process is
illustrated using one question from the HPI-CI related to the important topic of
antibiotic resistance. The frequencies with which students chose particular
multiple-choice responses for this question were highly correlated between
institutions, implying common underlying misconceptions. Examination of student
explanations using our analysis approach, coupled with group discussions within
and between institutions, revealed patterns in student thinking to the
participating faculty. Similar application of a two-tiered concept inventory by
general microbiology instructors, either individually or in groups, at other
institutions will allow them to better understand student thinking related to key
concepts in their curriculum.
PMID- 28512514
TI - First-Year and Non-First-Year Student Expectations Regarding In-Class and Out-of
Class Learning Activities in Introductory Biology.
AB - National calls for teaching transformation build on a constructivist learning
theory and propose that students learn by actively engaging in course activities
and interacting with other students. While interactive pedagogies can improve
learning, they also have the potential to challenge traditional norms regarding
class participation and learning strategies. To better understand the potential
openness of students to interactive teaching practices, we administered a survey
during the first week of two sections of an introductory biology course to
characterize how students envisioned spending time during class as well as what
activities they expected to complete outside of class during non-exam weeks and
in preparation for exams. Additionally, we sought to test the hypothesis that the
expectations of first-year students differed from those of non-first-year
students. Analyses of closed-ended and open-ended questions revealed that
students held a wide range of expectations and that most students expressed
expectations consistent with some degree of transformed teaching. Furthermore,
first-year students expected more active learning in class, more out-of-class
coursework during non-exam weeks, and more social learning strategies than non
first-year students. We discuss how instructor awareness of incoming student
expectations might be used to promote success in introductory science courses.
PMID- 28512515
TI - Biofilms for Babies: Introducing Microbes and Biofilms to Preschool-Aged
Children.
PMID- 28512516
TI - A Simple Activity to Enhance the Learning Experience of Reading Primary
Literature.
PMID- 28512518
TI - Development of Oral Communication Skills by Undergraduates that Convey
Evolutionary Concepts to the Public.
PMID- 28512519
TI - An Internship May Not Be Enough: Enhancing Bioscience Industry Job Readiness
through Practicum Experiences.
AB - In contrast to the narrowing of options in academic careers, the bioscience
industry offers robust employment opportunities for STEM-trained workers,
especially those who display both scientific and business talent. Unfortunately,
traditional science programs typically lack curricular features that develop this
type of worker. The North Carolina State University Master of Microbial
Biotechnology (MMB) program facilitates industry-specific experiential learning
to fill this training gap. Similar programs often rely on a single industry
internship to provide students relevant work experience, but completion of one
internship might not suffice to position students for employment in a highly
competitive job market. The MMB program requires students to complete an
internship and three practicum projects in an industry setting, to promote
development of key skills in a variety of areas, to build confidence in the
ability to perform initial job duties, and to establish a more extensive work
history in industry. In this Perspective we discuss an unmet need in
undergraduate and graduate STEM education that can be filled by incorporating a
similar set of industry-specific work experiences for students who desire to
transition from academe into the life science industry.
PMID- 28512517
TI - siRNA Immunological Fishing Training (SIFT) Experience as a Novel Research
Education Tool for Students Studying Immunology.
PMID- 28512521
TI - Using Pre-Assessment and In-Class Questions to Change Student Understanding of
Molecular Movements.
AB - Understanding how different types of molecules move through cell membranes is a
fundamental part of cell biology. To identify and address student misconceptions
surrounding molecular movement through cell membranes, we surveyed student
understanding on this topic using pre-class questions, in-class clicker
questions, and subsequent exam questions in a large introductory biology course.
Common misconceptions identified in student responses to the pre-class assessment
questions were used to generate distractors for clicker questions. Two-tier
diagnostic clicker questions were used to probe incoming common student
misconceptions (first tier) and their reasoning (second tier). Two subsequent
lectures with assessment clicker questions were used to help students construct a
new framework to understand molecular movement through cell membranes. Comparison
of pre-assessment and post-assessment (exam) performance showed dramatic
improvement in students' understanding of molecular movement: student answers to
exam questions were 74.6% correct with correct reasoning while only 1.3% of the
student answers were correct with correct reasoning on the pre-class assessment.
Our results show that students' conceptual understanding of molecular movement
through cell membranes progressively increases through discussions of a series of
clicker questions and suggest that this clicker-based teaching strategy was
highly effective in correcting common student misconceptions on this topic.
PMID- 28512522
TI - Photo Animation Brings Scientists Back to Life in the Classroom.
PMID- 28512523
TI - Student Buy-In Toward Formative Assessments: The Influence of Student Factors and
Importance for Course Success.
AB - Formative assessment (FA) techniques, such as pre-class assignments, in-class
activities, and post-class homework, have been shown to improve student learning.
While many students find these techniques beneficial, some students may not
understand how they support learning or may resist their implementation.
Improving our understanding of FA buy-in has important implications, since buy-in
can potentially affect whether students fully engage with and learn from FAs. We
investigated FAs in 12 undergraduate biology courses to understand which student
characteristics influenced buy-in toward FAs and whether FA buy-in predicted
course success. We administered a mid-semester survey that probed student
perceptions toward several different FA types, including activities occurring
before, during, and after class. The survey included closed-ended questions
aligned with a theoretical framework outlining key FA objectives. We used factor
analysis to calculate an overall buy-in score for each student and general linear
models to determine whether certain characteristics were associated with buy-in
and whether buy-in predicted exam scores and course grades. We found that unfixed
student qualities, such as perceptions, behaviors, and beliefs, consistently
predicted FA buy-in, while fixed characteristics, including demographics,
previous experiences, and incoming performance metrics, had more limited effects.
Importantly, we found that higher buy-in toward most FA types predicted higher
exam scores and course grades, even when controlling for demographic
characteristics and previous academic performance. We further discuss steps that
instructors can take to maximize student buy-in toward FAs.
PMID- 28512524
TI - Promoting the Multidimensional Character of Scientific Reasoning.
AB - This study reports part of a long-term program to help students improve
scientific reasoning using higher-order cognitive tasks set in the discipline of
cell biology. This skill was assessed using problems requiring the construction
of valid conclusions drawn from authentic research data. We report here efforts
to confirm the hypothesis that data interpretation is a complex, multifaceted
exercise. Confirmation was obtained using a statistical treatment showing that
various such problems rank students differently-each contains a unique set of
cognitive challenges. Additional analyses of performance results have allowed us
to demonstrate that individuals differ in their capacity to navigate five
independent generic elements that constitute successful data interpretation:
biological context, connection to course concepts, experimental protocols, data
inference, and integration of isolated experimental observations into a coherent
model. We offer these aspects of scientific thinking as a "data analysis skills
inventory," along with usable sample problems that illustrate each element.
Additionally, we show that this kind of reasoning is rigorous in that it is
difficult for most novice students, who are unable to intuitively implement
strategies for improving these skills. Instructors armed with knowledge of the
specific challenges presented by different types of problems can provide specific
helpful feedback during formative practice. The use of this instructional model
is most likely to require changes in traditional classroom instruction.
PMID- 28512526
TI - The Founding of a Journal.
PMID- 28512527
TI - The Future of CaJEM.
PMID- 28512525
TI - H2S Donor NaHS Changes the Production of Endogenous H2S and NO in D-Galactose
Induced Accelerated Ageing.
AB - Aims. The study was designed to explore whether hydrogen sulphide (H2S) and
nitric oxide (NO) generation changed in D-galactose- (D-gal-) induced ageing, the
possible effects of exogenous H2S supplementation, and related mechanisms.
Results. In D-gal-induced senescent mice, both H2S and NO levels in the heart,
liver, and kidney tissues were decreased significantly. A similar trend was
observed in D-gal-challenged human umbilical vein endothelial cells (HUVECs).
Sustained H2S donor (NaHS) treatment for 2 months elevated H2S and NO levels in
these mice, and during this period, the D-gal-induced senescent phenotype was
reversed. The protective effect of NaHS is associated with a decrease in reactive
oxygen species levels and an increase in antioxidants, such as glutathione, and
superoxide dismutase and glutathione peroxidase activities. Increased expression
of the H2S-producing enzymes cystathionine gamma-lyase (CSE) and cystathionine
beta-synthase (CBS) in the heart, liver, and kidney tissues was observed in the
NaHS-treated groups. NaHS supplementation also significantly postponed D-gal
induced HUVEC senescence. Conclusions. Endogenous hydrogen sulphide production in
both ageing mice and endothelial cells is insufficient. Exogenous H2S can
partially rescue ageing-related dysfunction by inducing endogenous H2S and NO
production and reducing oxidative stress. Restoring endogenous H2S production may
contribute to healthy ageing, and H2S may have antiageing effects.
PMID- 28512528
TI - Introducing the New Editor-In-Chief.
PMID- 28512529
TI - From the Cal/AAEM representative on the CAL/ACEP Governmental Affairs Committee.
PMID- 28512530
TI - Resident/Student Corner.
PMID- 28512531
TI - Pro Position for Filming in The ED.
PMID- 28512533
TI - Rebuttal to "Saying No..."
PMID- 28512532
TI - Saying No to Cameras in the Emergency Department.
PMID- 28512534
TI - Rebuttal to "Pro Filming in the ED".
PMID- 28512535
TI - Evaluation of surface roughness of enamel after various bonding and clean-up
procedures on enamel bonded with three different bonding agents: An in-vitro
study.
AB - BACKGROUND: The purpose of this study was to analyze and compare the enamel
surface roughness before bonding and after debonding, to find correlation between
the adhesive remnant index and its effect on enamel surface roughness and to
evaluate which clean-up method is most efficient to provide a smoother enamel
surface. MATERIAL AND METHODS: 135 premolars were divided into 3 groups
containing 45 premolars in each group. Group I was bonded by using moisture
insensitive primer, Group II by using conventional orthodontic adhesive and Group
III by using self-etching primer. Each group was divided into 3 sub-groups on the
basis of type of clean-up method applied i,e scaling followed by polishing,
tungsten carbide bur and Sof-Lex disc. Enamel surface roughness was measured and
compared before bonding and after clean-up. RESULTS: Evaluation of pre bonding
and post clean-up enamel surface roughness (Ra value) with the t test showed that
Post clean-up Ra values were greater than Pre bonding Ra values in all the groups
except in teeth bonded with self-etching primer cleaned with Sof-Lex disc.
Reliability of ARI score taken at different time interval tested with Kruskal
Wallis test suggested that all the readings were reliable. CONCLUSIONS: No clean
up procedure was able to restore the enamel to its original smoothness. Self
etching primer and Sof-Lex disc clean-up method combination restored the enamel
surface roughness (Ra value) closest to its pre-treatment value. Key words:Enamel
surface roughness, clean-up method, adhesive remnant index.
PMID- 28512536
TI - Effect of Smear Clear and Some Other Commonly Used Irrigants on dislodgement
resistance of Mineral Trioxide Aggregate to Root Dentin.
AB - BACKGROUND: This study aimed to assess the push-out bond strength of mineral
trioxide aggregate (MTA) to root canal dentin after irrigation with Smear Clear
in comparison with 2.5% sodium hypochlorite (NaOCl), 2% chlorhexidine (CHX) and
saline as commonly used root canal irrigants. MATERIAL AND METHODS: The coronal
and mid-root areas of maxillary anterior teeth were horizontally sectioned into
one-millimeter thick slices. The root canal lumen of dentinal slices was dilated
using a diamond bur with 1.3 mm diameter. After the application of MTA, the
samples were incubated in 100% humidity for 10 minutes and were then randomly
divided into four groups (n=20) and immersed in Smear Clear, 2.5% NaOCl, 2% CHX
and saline for 30 minutes. No irrigant was used for the control group (n=20). A
wet cotton pellet was placed on the samples and after 48 hours of incubation,
push-out bond strength was measured using a universal testing machine. The
samples were evaluated under a stereomicroscope to determine the mode of failure.
One-way ANOVA was used to assess statistical differences among the groups.
RESULTS: The control group showed the highest bond strength with significant
differences with other groups (P<0.05). Among the experimental groups, the saline
group had no significant difference with CHX (P=0.09) but it had significant
differences with Smear Clear and NaOCl groups (P<0.05). No significant difference
in bond strength to MTA was noted after irrigation with Smear Clear, CHX and
NaOCl (P>0.05). Other pairwise comparisons showed no significant difference
(P>0.05). CONCLUSIONS: Irrigation with Smear Clear, CHX and NaOCl did not cause a
significant change in bond strength of MTA to dentin. Key words:Root Canal
Irrigants, push-out, Mineral Trioxide Aggregate, dentin.
PMID- 28512537
TI - Decreased dentin tubules density and reduced thickness of peritubular dentin in
hyperbilirubinemia-related green teeth.
AB - BACKGROUND: It is stated anecdotally that patients with liver diseases in
childhood who develop green teeth have increased risk for rampant caries, which
may be secondary to changes in dental structure. The aim of this study was to
test the hypothesis that hyperbilirubinemia affects the dentin morphology of
green teeth. MATERIAL AND METHODS: Sixteen primary teeth were prepared and
divided into two groups (green teeth, n = 8 and control, n = 8), which were
transversely fractured across the cervical third of the dental crowns; dentin was
prepared and sputter-coated with gold, and examined under a scanning electron
microscope. The mean density and mean diameter of dentin tubules, as well as the
thickness of peritubular dentin, were compared. RESULTS: Hyperbilirubinemia was
associated with a decrease in the density of the dentin tubules (p< .01) and the
thickness of peritubular dentin of green teeth (p< .01). CONCLUSIONS: There was a
correlation between childhood hyperbilirubinemia and changes in the dentin
morphology, including a decrease in the density of the dentin tubules and a
reduction in the thickness of peritubular dentin in green teeth. Key
words:Hyperbilirubinemia, liver disease, childhood, dentin tubules, human teeth,
scanning electron microscopy.
PMID- 28512538
TI - Oral hygiene and periodontal health status among khat chewers. A case-control
study.
AB - BACKGROUND: Habitual khat chewing is a widespread male habit in Southern Arabia
and East Africa. The aim of this study was to assess the effect of Khat chewing
on oral hygiene and periodontal health status among Yemeni male khat chewers.
MATERIAL AND METHODS: This case- control study included 310 khat chewers, aged 20
65 years, and 72 age- and gender- matched non-chewers as controls. Periodontal
examination included recording of dental plaque index (PI), gingival index (GI),
probing pocket depth (PPD), attachment level (AL) and gingival recession (GR).
Demographic data, oral hygiene practices, and duration, frequency and site of
khat chewing were obtained using questionnaires. SPSS was used for data analysis.
ANOVA and t- tests were used to compare groups. RESULTS: Khat chewers had
significantly higher mean PI, AL, GR scores than non-chewers (P < 0.05). However,
no significant differences in the GI and PPD mean scores were observed between
both groups (p > 0.05). Interestingly, the results showed that the chewing side
had less PI, GI and PPD than non-chewing side. However, gingival recession was
significantly higher in the chewing side. The duration of chewing showed a
significant effect on PI, PPD, AL, and GR but had no effect on the gingival
condition. Likewise, the frequency of chewing showed a significant effect on PPD,
AL, and GR, but had no effect on other indices (PI and GI). CONCLUSIONS: The
results of this study indicate that khat chewing have a detrimental effect on the
periodontium. Key words:Khat chewing, periodontal health, oral hygiene.
PMID- 28512539
TI - Longitudinal effects of rapid maxillary expansion on masticatory muscles
activity.
AB - BACKGROUND: To investigate the modifications induced by rapid maxillary expansion
(RME) on the electromyographic (EMG) activities of the anterior temporal and
superficial masseter muscles, in patients without pre-treatment EMG alterations.
MATERIAL AND METHODS: Twenty-one patients with unilateral posterior cross-bite
selected from the orthodontic department of the University of L'Aquila (Italy),
were enrolled. There was no control group in this study since each subject acted
as a control of her/himself. Two surface EMG recordings were taken: T0 (before
RME) and at T1 (3 month after the end of expansion). To verify the neuromuscular
equilibrium, the EMG activities of both right and left masseter and anterior
temporal muscles were recorded during a test of maximum clench. EMG indexes were
compared by paired Student's t-test. RESULTS: In both occasions, all indices
showed a good symmetry between the right and left side masticatory muscles. No
statistically significant differences were found between the two recordings.
CONCLUSIONS: In children without pre-treatment EMG alterations, no variations in
standardized muscular activity after RME were found. The treatment did not alter
the equilibrium of the masseter and temporal muscles. Key words:Rapid maxillary
expansion, electromyography, masticatory muscles.
PMID- 28512540
TI - The effects of three remineralizing agents on regression of white spot lesions in
children: A two-week, single-blind, randomized clinical trial.
AB - BACKGROUND: This study investigated the effect of three remineralizing agents on
improving white spot lesions (WSLs). MATERIAL AND METHODS: This clinical trial
included children who had at least one WSL on anterior teeth of upper or lower
jaws. The participants were randomly assigned to 4 groups by treatment: 1) a
cream containing casein phosphopeptide-amorphous calcium phosphate and fluoride
(MI Paste Plus); 2) a cream containing hydroxyapatite and fluoride (Remin Pro);
3) a 2% sodium fluoride gel; and 4) usual home care (control). The treatment was
performed for 3 times over 10 days using special trays for retaining
remineralizing agents. The area and mineral content of WSLs were measured at
baseline (T1) and 1 day after finishing treatment (T2). Blinding was applied for
outcome assessment. RESULTS: Eighty patients were assigned to MI Paste Plus,
Remin Pro, NaF or control groups. The application of all remineralizing agents
caused a significant decrease in area and a significant increase in mineral
content of WSLs (p<0.05), whereas the control patients did not experience any
significant alteration (p>0.05). At T2, the area of WSLs was significantly lower
in three experimental groups compared to the control group (p=0.023), but between
group difference in mineral content of WSLs failed to achieve statistical
significance (p=0.08). CONCLUSIONS: The in-office application of either MI Paste
Plus or Remin Pro was as effective as 2% NaF for reducing area and increasing
mineral content of WSLs. MI Paste Plus and Remin Pro could be recommended as
suitable alternatives to NaF for managing WSLs. Key words:White spot lesion,
caries, casein phosphopeptide-amorphous calcium phosphate, hydroxyapatite, sodium
fluoride, CPP-ACP, MPlus, Remin Pro, NaF.
PMID- 28512541
TI - Anti-plaque and anti-gingivitis effect of Papain, Bromelain, Miswak and Neem
containing dentifrice: A randomized controlled trial.
AB - BACKGROUND: Patients undergoing fixed orthodontic therapy may have difficulty in
maintaining a good oral hygiene due to the difficulty posed by the appliances in
accessing such areas. This study aimed to compare anti-plaque and anti-gingivitis
efficacy of dentifrice containing Papain, Bromelain, Miswak and Neem with a
standard dentifrice among patient's undergoing fixed orthodontic treatment.
MATERIAL AND METHODS: Single center, single blind, parallel arm, randomized
controlled clinical trial with an allocation ratio of 1:1 was conducted.
Evaluation of plaque and gingivitis was done using Williams modification of
Silness and Loe Plaque Index (PI) for use in orthodontic subjects and Loe and
Silness's Gingival Index (GI) at baseline and one month. RESULTS: Inter-group
comparison showed there was significantly lower mean plaque index in test (0.88
+/-0.05) than in control group (1.17 +/-0.05) after adjusting for the baseline
plaque index (p<0.001). Similarly, there was significantly lower mean gingival
index in test (0.87 +/-0.04) than in control group (1.14 +/-0.04) after adjusting
for the baseline gingival index (p<0.001). CONCLUSIONS: The efficacy of the test
dentifrice in limiting plaque and gingivitis suggests that it can be used as a
home based adjunct to clinical therapy in orthodontic patients. Key
words:Bromelain, gingivitis, miswak, neem, papain, plaque.
PMID- 28512542
TI - Cambra system in patients awaiting hematopoietic progenitor cell transplant and
high caries risk.
AB - BACKGROUND: Recent times have witnessed a significant increase in the number of
patients affected by problems related to oncological treatment Aims of this study
is to evaluate dental affectation among patients awaiting hematopoietic
progenitor cell transplant (HPCT), and they showed high caries risk, so it should
establish a protocol prior to transplantation. MATERIAL AND METHODS: The study
included 72 patients due for HPCT. Clinical and radiological explorations were
performed and oral photos taken. The amount of caries, missing teeth and fillings
were registered for each patient. CAO, DMFS and Restoration Indices were
calculated. RESULTS: 83% of patients presented caries. 48 patients (67%) had lost
at least one tooth. Only 32 patients (44%) had received some sort of conservative
treatment. The average CAO index value obtained was 10.37. The DMFS index showed
an average of 27.06 affected surfaces. Of the 72 patients studied, 40 (56%)
showed a restoration index value of zero. CONCLUSIONS: These patients presented a
high number of carious teeth and a low restoration index. The presence of so many
possible septic foci in an individual, who will later become susceptible to
infection, highlights the importance of preventative treatment and bucco-dental
restoration within this patient population. These patients with a high caries
risk can be treated with CAMBRA system. Key words:Hematopoietic progenitor cell
transplantation, high caries risk, state of oral health, haematological disease,
CAMBRA system.
PMID- 28512543
TI - Tensile strength and impact strength of color modified acrylic resin reinforced
with titanium dioxide nanoparticles.
AB - BACKGROUND: Poor mechanical properties are among the main limitations of acrylic
resins. Addition of titanium dioxide (TiO2) nanoparticles to acrylic resin has
been shown to improve its mechanical properties with an adverse effect on its
color. Thus, this study sought to assess the tensile and impact strength of a
color modified heat cure acrylic resin reinforced with TiO2 nanoparticles.
MATERIAL AND METHODS: In this in vitroexperimental study, 1wt% TiO2 nanoparticles
were added to SR Triplex Hot heat-cure acrylic resin powder and mixed. Pigments
and color fibers were also added and 18 samples were fabricated of this paste for
tensile and impact strength testing (n=9) according to ISO5271. Eighteen control
samples were also fabricated from the acrylic powder without any modification.
Independent t-test was used for data analysis (P< 0.05). RESULTS: The mean
tensile strength of the reinforced group was found to be significantly higher
(difference of 11 MPa) than that of the control group (P=0.001). The mean impact
strength of the reinforced group was 7 MPa higher than that of the control group
and this difference was statistically significant as well (P=0.001). CONCLUSIONS:
The color modified acrylic resin reinforced with 1wt% TiO2 showed significantly
higher tensile and impact strength compared to the conventional acrylic resin.
Thus, TiO2 nanoparticles may be incorporated into color-modified acrylic resin
powder to enhance its tensile and impact strength, given that they have no
adverse effect on other properties. Key words:Tensile strength, acrylic resins,
titanium dioxide, impact strength.
PMID- 28512544
TI - Oral health related quality-of-life outcomes of partially edentulous patients
treated with implant-supported single crowns or fixed partial dentures.
AB - BACKGROUND: Oral health-related quality of life (OHRQoL) is afflicted by
different variables. Limited information is available regarding the impact of
different phases of implant therapy on OHRQoL of edentulous patients. This study
was carried out to assess the OHRQoL of patients treated with implant-supported
single crowns or fixed partial dentures. MATERIAL AND METHODS: A total of 79
healthy partially edentulous subjects needing implant therapy were incorporated
in this study. Before placement of the implants, the subjects were instructed to
fill the original version of OHIP questionnaire. Subsequently patients received
titanium oral implants of the ITI(r) Dental Implant System. After 1st, 2nd and
3rd year of implant placement, patients filled the same OHIP-49 questionnaire. In
this manner the impact of implant therapy on OHRQoL by putting in comparison pre-
and post-treatment OHIP-49 scores was assessed. Statistical analyses were
performed using Statistical Package for the Social Science software (SPSS,
version 22, Chicago, IL, USA). Paired t test and Unpaired t test were performed
and a statistical significance was set at 5% level of significance (p<0.05).
RESULTS: Functional limitation, physical pain, psychological discomfort, physical
disability, psychological disability, social disability were significantly
decreased from baseline to 1st year (p<0.05) except handicap (p>0.05). All
variables were also significantly decreased from baseline to 2nd year and 3rd
year (p<0.05). There were no significant differences dependent on gender with
respect to OHIP (p>0.05). Patients aged less than 60 years and more than 60 years
of age groups differed significantly with respect to OHIP scores measured at 1st
year, 2nd year and at 3rd year of implant placement (p<0.05). CONCLUSIONS:
Decrease in pre- and post-treatment OHIP scores OHIP demonstrated the significant
increase in the OHRQoL after the therapy, which suggested increased levels of
patient satisfaction. Key words:Edentulism, dental implants, Oral health-related
quality-of-life.
PMID- 28512545
TI - Effect of hemostatic agent on marginal gaps of class V giomer restorations.
AB - BACKGROUND: Contamination of dentin with hemostatic agents might exert a
deleterious effect on adhesive procedures on dentin. The present study was
undertaken to investigate the effect of aluminum chloride hemostatic agent on
marginal gaps in Cl V giomer restorations. MATERIAL AND METHODS: Fifty sound
bovine permanent incisors were selected for the purpose of this in vitro study
and Cl V cavities were prepared on their buccal surfaces; the gingival margins of
the cavities were placed in dentin. The tooth samples were randomly assigned to
two groups (n=25). The samples in groups 1 and 2 underwent a restorative
procedure without and with the application of aluminum chloride hemostatic agent
in the cavity, respectively, before application of the adhesive. BeautiBond one
step self-etch adhesive and Beautifil II giomer restorative material were used
for the restoration of the cavities in both groups. The samples were thermocycled
and sectioned, followed by measuring the gap sizes at gingival margins in um
under a stereomicroscope. The marginal gaps were compared with Mann-Whitney U
test. Statistical significance was set at P<0.05. RESULTS: The results showed
significant differences in the mean marginal gaps between the two groups under
study (P<0.001); the mean marginal gaps were higher in group 2 (with hemostatic
agent) compared to those in group 1 (without hemostatic agent) (P<0.0005).
CONCLUSIONS: Contamination with aluminum chloride hemostatic agent in giomer
restorations gave rise to higher gingival margin gaps. Key words:Dental
adhesives, giomer restorative material, hemostatic agent, marginal adaptation.
PMID- 28512547
TI - Vascular labeling of the head and neck vessels: Technique, advantages and
limitations.
AB - BACKGROUND: Vascular staining techniques have been used to describe the vascular
structures of several anatomic areas. However, few reports have described this
procedure in the head and neck region. This paper describes a head and neck
vascular labeling procedure, and describes some of the technical complications
that may occur. MATERIAL AND METHODS: Fifteen specimen cadaver heads were
prepared. After drying the vascular system, the internal carotid arteries were
ligated and a solution with latex and a gelling agent was injected into the
internal carotid arteries and external jugular veins. Two different colors were
employed to differentiate arteries from veins. A total of 60ml latex was injected
into each blood vessel. Subsequently, the specimens were refrigerated at 5
degrees C for a minimum of 24 hours. Finally, a dissection was performed to
identify the venous and arterial systems of the maxillofacial region. RESULTS: In
most specimens, correct identification of the vascular structures (lingual
artery, pterigoyd plexus, and the major palatal arteries, among others) was
possible. However, in three heads a major technical problem occurred (the latex
remained liquid), making the dissection unfeasible. Other minor complications
such as latex obstruction due to the presence of atheromas were found in two
further specimens. CONCLUSIONS: The vascular labeling technique is a predictable,
effective and simple method for analyzing the vascular system of the
maxillofacial area in cadaveric studies, including vessels of reduced diameter or
with an intraosseous course. This procedure can be especially useful to teach
vascular anatomy to dental students and postgraduate residents. Key words:Blood
vessels, vascular casting, vascular labeling, head and neck arteries, carotid
arteries, jugular veins.
PMID- 28512546
TI - Evaluation of the effect of different enamel surface treatments and waiting times
on the staining prevention after bleaching.
AB - BACKGROUND: Bleached dental enamel can be more susceptible to staining than the
enamel that has never been bleached, especially right after tooth bleaching. The
aim of this study is to evaluate the effect of surface treatments and waiting
time prior to contact with dye on bleached enamel staining susceptibility.
MATERIAL AND METHODS: One hundred teeth were bleached with 35% hydrogen peroxide
(Whiteness HP, FGM) and randomly assigned to G1 artificial saliva, G2 2% sodium
fluoride (Flugel, Nova DFL), G3 casein phosphopeptide-amorphous calcium phosphate
fluoride paste (CPP-ACPF, MI Paste Plus, GC America), G4 rinse for color
maintenance after bleaching (Keep White Rinse, DMC) and G5 polishing with
aluminum oxide-impregnated disks (Super Buff Disk, Shofu). Fifty specimens were
immersed in red wine for 15 minutes, immediately after treatment, and the others
one hour after. Color difference (?E) was evaluated with a spectrophotometer
(Vita EasyShade). Surface treatments and waiting time effects were analyzed with
Kruskal-Wallis and Mann Whitney tests (p<0.05). RESULTS: Surface treatments
(p>0.05) and waiting time (p>0.05) were not significant to decrease bleached
enamel susceptibility to red wine staining. CONCLUSIONS: Surface treatments were
similar to artificial saliva for bleached enamel susceptibility to red wine
staining. Immediate or one-hour-postponed contact with red wine did not affect
bleached enamel color. Key words:Tooth bleaching, color, dental enamel, hydrogen
peroxide, pigmentation.
PMID- 28512548
TI - Relationship between pulp-tooth volume ratios and chronological age in different
anterior teeth on CBCT.
AB - BACKGROUND: The CBCT imaging technique exhibits proper accuracy to determine the
internal anatomy of teeth. Therefore, this technique can use to estimate age by
measuring the amount of decrease in the volume of the pulpal cavity of teeth. The
aim of the present study was to evaluate the correlation between chronological
age and pulp-to-tooth volume ratios in anterior teeth with the use of the CBCT
technique and to determine a regression model to estimate human age. MATERIAL AND
METHODS: In this present descriptive-analytical study, 122 subjects (46 males and
76 females), with an age range of 13-70 years, were evaluated. The MIMICS
software program was used to determine the pulp-to-tooth volume ratios in 732
anterior teeth. Regression analysis was used to assess the correlation between
age and pulp to tooth volume ratios. RESULTS: In all the teeth evaluated, there
was an inverse and significant correlation between age and the pulp-to-tooth
volume ratios in males and females, with a stronger correlation in males. In
addition, such a correlation was stronger in maxillary central incisors and
canines. In the model in which the mean of ratios in anterior teeth was used to
estimate age the correlation was stronger compared to that in single tooth.
CONCLUSIONS: In general, the results of the present study showed that it is
advisable to use the mean of all the ratios of anterior teeth in forensics to
estimate age. Key words:Age estimation , cone-beam CT, forensic dentistry,
secondary dentin, pulp cavity.
PMID- 28512549
TI - Evaluation of the effectiveness of the photobiomodulation in the treatment of
dentin hypersensitivity after basic therapy. A randomized clinical trial.
AB - BACKGROUND: Dentin hypersensitivity (DH) in one of the most common causes of
patient discomfort in the general population and its prevalence is higher in
patients who have received basic or surgical periodontal treatment. Efficiency of
the diode laser with different wavelengths has been studied by several authors,
showing an improvement rate of the DH between 60-98%. The aim of the present
study was to evaluate the effect of photobiomodulation (PBM) treatment on the
reduction of DH after non surgical periodontal treatment. MATERIAL AND METHODS: A
randomized split mouth clinical trial was performed involving 30 patients (120
teeth) diagnosed with DH after scaling and root planning. Two teeth of the
experimental side were treated with the laser and 2 teeth of the control side
were treated without activating the laser. The laser treatment parameters for
each tooth were 660nm, 200mW, CW, illuminated area 1.15cm2, 173mW/cm2, 60
seconds, 12 J, 10.4J/cm2. Age, gender, smoking, plaque index, gingival recession,
probing and VAS (for tactile and thermal stimulation) were registered before the
laser treatment, immediate post treatment (after 2 minutes), 2 weeks, 1 month and
2 months after treatment. RESULTS: There was significant difference (p<0.01) in
discomfort to thermal and mechanical stimulation between the control and diode
laser treatment sites at all evaluation periods. The level of discomfort
decreased immediately following diode laser therapy, and continued to demonstrate
a decrease for the duration of the study. All teeth remained vital after laser
treatment, without adverse reactions or complications. CONCLUSIONS: The PBM can
be used to reduce DH without detrimental pulpal effects. Key words:Dental
hypersensitivity, laser, diode laser, photobiomodulation.
PMID- 28512550
TI - Analysis of scientific production in spanish implantology.
AB - BACKGROUND: The aim of the study was to quantify the scientific productivity of
researchers, organizations, and regions in Spain that publish articles on
implantology in dental journals indexed in Journal Citation Reports. MATERIAL AND
METHODS: A search was conducted among the core collection of Thomson Reuters' Web
of Science database, on the basis of its broad thematic and geographic coverage
of health sciences. The search identified original articles - the main vehicle
for the dissemination of research results. The search was conducted in July 2016,
applying the truncated search term 'implant*' to locate original articles on
implantology and its derivative forms. The search was conducted within the topic
field (title, keywords and abstract) and two inclusion criteria were applied:
documents denominated as articles were included; and articles categorized as Web
of Science Medicine Dentistry and Oral Surgery. Finally only articles for which
one of the participating organizations was located in Spain were selected.
RESULTS: The final search identified a total of 774 records. The period 1988 to
2015 saw an exponential growth in scientific production, especially during the
last 10 years. Clinical Oral Implants Research and Medicina Oral Patologia Oral y
Cirugia Bucal (Oral Medicine, Oral Pathology, and Oral Surgery) were the most
productive journals. Collaborative networks among authors and among institutions
increased and this increase was related to the improving quality of the
publications. CONCLUSIONS: Bibliometric analysis revealed a significant growth in
the quantity and quality of Spanish implantology literature. Most key
bibliometric indicators demonstrated upward trends. Key words:Bibliometric
analysis, publication, keywords, implantology, implant.
PMID- 28512551
TI - Consensus statements and clinical recommendations on treatment indications,
surgical procedures, prosthetic protocols and complications following All-On-4
standard treatment. 9th Mozo-Grau Ticare Conference in Quintanilla, Spain.
AB - OBJECTIVES: The present consensus report critically evaluates the scientific
evidence based on a comprehensive systematic review of the All-On-4 treatment
concept, focusing primarily on the treatment indications, surgical procedures and
prosthetic protocols, and secondarily on the mechanical and biological
complications involved. MATERIAL AND METHODS: A systematic review was made in
advance of the meeting. Consensus statements, treatment guidelines and
recommendations for future research were based on within-group as well as plenary
debates and discussions of the systematic review. RESULTS: The main indication of
All-On-4 standard care is an atrophic maxilla or mandible, with or without
remnant hopeless tooth. in ASA I or II patients. This surgical-prosthetic
protocol seems efficient, safe and effective in the case of Cawood & Howell class
IV, V and VI. It is necessary for the implant to have had an insertion torque of
over 35 Ncm for immediate loading. The provisional prosthesis should provide
rigidity, being non-flexible in order to avoid micro-movements, and should be
strong enough to not fracture. Balanced occlusion without interferences is
required, ensuring very gentle dynamic movements. The design of the definitive
prosthesis must be cleanable and biomechanically adjusted to the implant position
and individual characteristics of each patient. A non-concave acrylic base
resting over soft tissue is recommended, facilitating hygiene. Regarding
occlusion, a group guide should be made, taking into account whether the
antagonist is not a removable complete denture. In that case, bi-balanced
occlusion should be assessed. Prosthetic complications occur as a result of
fractures of the provisional acrylic prostheses. These problems in turn can be
resolved by repair through relining or fixing. The most frequent biological
complication is the loss of at least one implant, while the second most frequent
complication is the development of peri-implantitis and mucositis. CONCLUSIONS:
In the treatment of atrophy for full-arch implant supported restorations it is
considered that four implants suffice for immediate loading and the final
prosthesis, even when there is available bone between the mental foramina or
maxillary sinuses. The weakness of the quality of the available evidence
indicates that further studies are needed, involving an appropriate design and
with adequate follow-up in All-On-4 standard care to confirm the present results
mainly in relation to survival rates and complications. Key words:Atrophic jaw,
All-on-4, immediate implant loading, edentulous mandible, edentulous maxilla,
tilted implant, implant failure, dental implants.
PMID- 28512553
TI - Juxtacortical Mandibular Chondrosarcoma during pregnancy: A case report.
AB - Chondrosarcoma is one of the most common malignant bone tumors in adults. It use
to affect upper arm, pelvis and thigh bone. A wide surgical extirpation represent
the gold standard to treat this disorder. In fact, radiotherapy and chemotherapy
are no useful. Interestingly, chondrosarcoma is rare in head and neck (HNCS) and
extremely uncommon during pregnancy. Thus, there is a lack of evidence about the
proper treatment in these cases. A wide surgical extirpation is also considered
the most effective procedure in HNCS. There are no consistent evidences about the
he role of radiation and chemotherapy. In view of that, the present study
describes a case of juxtacortical mandibular chondrosarcoma affecting a 28-year
old pregnant woman. After a multidisciplinary analysis of the case, we decided to
treat the patient with a wide surgical resection and and immediately
reconstruction. Key words:Mandibular chondrosarcoma, pregnancy, surgical
extirpation, radiotherapy, chemoteraphy.
PMID- 28512552
TI - Ability of salivary biomarkers in the prognostic of systemic and buccal
inflammation.
AB - Nowadays, there is a growing interest in using saliva as an alternative sample
for the diagnosis, prediction and progression of several diseases. It has been
established that some molecules found in saliva are related to oral inflammatory
processes and systemic health status. Furthermore, it is known that saliva is
crucial for the carrying out of different functions in the oral cavity and its
role in the local modulation of inflammatory and immune response is being
thoroughly studied by the health research community. The aim of this review is to
analyze the most important biomarkers which have been utilized in biomedicine
during the last two decades in order to establish a correlation between certain
specific salivary biomarkers and systemic inflammation. Then, we discuss the
utility of total proteins, immunoglobulin A and alpha-amylase as biomarkers for
the prognostic of local inflammation after oral surgery. Key words:Inflammation,
salivary biomarkers, systemic disease, buccal surgery, total proteins,
inmunoglobulin A, Alpha-amylase.
PMID- 28512554
TI - A case report on dental management of a toddler with Pachygyria.
AB - Children with special health care needs receive less oral care than the normal
population, inspite of the high level of dental diseases among them. They are at
an increased risk for oral diseases throughout their lifetime. This paper reports
a case of a toddler with congenital unusual thick convolutions of the cortex
resulting in a condition called pachygyria. Intra oral examination showed
multiple abscesses with poor oral hygiene. As the patient was lacking cooperative
ability, treatment of full mouth rehabilitation as needed. The parents were
advised for regular dental check-ups and informed about maintenance of good oral
hygiene. This case report demonstrates the importance of oral hygiene maintenance
of special children and also about their short and long term dental treatment
protocol for maintaining good oral health. Key words:Pachygyria, general
anaesthesia, special child, health care needs, preventive measures.
PMID- 28512555
TI - Assessment of Obesity and Hepatic Late Adverse Effects in the Egyptian Survivors
of Pediatric Acute Lymphoblastic Leukemia: a Single Center Study.
AB - BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) with current cure rates
reaching 80% emphasizes the necessity to determine treatment-related long-term
effects. The aim of this study is to estimate the prevalence of overweight,
obesity, and hepatic late adverse effects in a cohort of ALL survivors treated at
the Hematology and Oncology Unit, Pediatrics Department, Menoufia University,
Egypt. METHODS: In this case-control study, height, weight, and body mass index
(BMI) were assessed for 35 pediatric ALL survivors and 35 healthy children. These
parameters were plotted on the growth and WHO standard deviation charts for both
males and females. Overweight and obesity were defined by BMI > 85th and 95th
percentile respectively. Laboratory investigations were done in the form of iron
profile, liver enzymes, total and direct bilirubin levels, serum urea &creatinine
and detection of hepatitis C virus antibodies by ELISA. RESULTS: The weight and
BMI were significantly greater in the survivors than controls (P value =0.002 and
0.039 respectively). ALT, total & direct bilirubin, serum ferritin and
transferrin saturation were considerably higher in the survivors than the
controls (P value = 0.03, 0.036, 0.044, 0.006 and 0.03 respectively). Ten (28.6%)
of survivors had hepatitis C antibodies with none (0%) of controls (P value
=0.02). CONCLUSIONS: Pediatric ALL survivors are at increased risk of
overweight/obesity, hepatic dysfunction in the form of elevated liver enzymes,
bilirubin levels, and C viral hepatitis. Screening of those survivors for such
complications should be considered.
PMID- 28512556
TI - Pediatric Tuberculosis in Northern Sardinia.
AB - BACKGROUND AND OBJECTIVES: Migration flux is an increasing phenomenon in Italy,
and it raises several public health issues and concerns in pediatric infectious
diseases. This study investigated the clinical characteristics and outcomes of a
pediatric population at high-risk for tuberculosis (TB) and the potential role of
immigration as a risk factor. DESIGN: We performed an observational retrospective
study of children referred to the only Pediatric Infectious Diseases Unit for
Northern Sardinia over a 6-year-period (2009-2014). Main variables assessed
included TB skin test (TST), confirmed by quantiFERON Gold in Tube test, thorax X
ray (TX), microbiological culture, direct microscopy for acid-fast bacilli and
molecular assays. RESULTS: Of the 246 children (mean age = 5.8 +/- 3.9 years)
identified, 222 (90.2%) were native to Sardinia and 24 (9.8%) were immigrants.
The majority of children (n=205; 83%) were TB-exposed but not infected based on a
negative TST and TX. Among the TST positive group (n= 39; 16%), 19 (49%) had
latent TB (TX negative), while 20 (51%) had active TB (TX positive). The percent
of TST positive children was significantly higher in the immigrant than the
native group (42.5% versus 14%, p<0.001). Clinical presentations included
pulmonary involvement with hilar lymphadenopathy (72%), pleurisy (13,5%), lateral
cervical lymphadenopathy (9%), pneumonia with calcifications (4.5%) and
disseminated TB (4.5%). One child had multidrug-resistant tuberculosis.
CONCLUSIONS: Pediatric TB represents a relevant and potentially worsening public
health problem in Northern Sardinia. A strict surveillance system and appropriate
treatment can prevent the most severe forms and reduce TB transmission.
PMID- 28512557
TI - Increased Vasoocclusive Crises in "O" Blood Group Sickle Cell Disease Patients:
Association with Underlying Thrombospondin Levels.
AB - OBJECTIVES: To explore the incidence of vaso-occlusive crisis (VOC) in Blood
Group "O" sickle cell disease (SCD) patients, and correlate it with the blood
group and thrombospondin (TSP) levels. METHODS: In 89 consecutive SCD patients,
blood samples were obtained for von Williebrand factor (vWF:Ag) antigen, collagen
binding activity (CBA), ristocetin binding activity (RCo), blood group typing, C
reactive protein (CRP), high performance liquid chromatography (HPLC), Serum TSP
1 and TSP 2 levels, complete blood counts (CBC), lactic dehydrogenase (LDH)
levels, liver function (LFT) and renal function tests (RFT) during VOC episodes
and in steady state conditions. RESULTS: In steady state SCD patients (n=72), "O"
blood group patients (n=37) showed a significantly higher median serum TSP 1 and
TSP 2 levels as compared to non-O blood group patients [n=35] [p <0.05, Mann
Whitney test]; with an inverse relation between vWF:Ag, Factor VIII:C and TSP
levels. Furthermore, the serum TSP 1 and TSP 2 levels were significantly higher
in patients presenting with acute VOC [n=17], as well as in those with repeated
VOC's (group 1, n=16), especially amongst blood group "O" patients [p, <0.05,
Mann-Whitney test]. CONCLUSIONS: The study demonstrates an inverse relation
between TSP and vWF levels, in blood group "O" SCD patients, with an upregulation
of the TSP levels. Expectedly, during active VOC crisis, the TSP 1 and TSP 2
levels were significantly elevated.
PMID- 28512558
TI - FDG-PET Scan: a new Paradigm for Follicular Lymphoma Management.
AB - In the present review, the reader will be led to the most relevant observations
that prompted oncologists and haematologist to consider FDG-PET/CT as a new
paradigm for FL management in clinical practice. The role of functional imaging
in lymphoma staging, restaging, prognostication, and metabolic tumour volume
computing will be reviewed in detail. Moreover, a special focus will be addressed
to technical and practical aspects of PET scan reporting, which have been set
during the last decade to ensure the reproducibility of the therapeutic results.
Finally, the predictive role of PET/CT on long-term treatment outcome will be
compared with another well-known prognosticator as minimal residual disease (MRD)
detection by Immunoglobulin gene rearrangement assessment.
PMID- 28512559
TI - Spirometric Evaluation of Pulmonary Function in Nigerian Children underwent Bone
Marrow Transplantation for Sickle Cell Anemia.
PMID- 28512560
TI - The Start-Up of the first Hematopoietic Stem Cell Transplantation Center in the
Iraqi Kurdistan: a Capacity-Building Cooperative Project by the Hiwa Cancer
Hospital, Sulaymaniyah, and the Italian Agency for Development Cooperation: an
Innovative Approach.
AB - We describe the entire process leading to the start-up of a hematopoietic stem
cell transplantation center at the Hiwa Cancer Hospital, in the city of
Sulaymaniyah, Kurdistan Iraqi Region. This capacity building project was funded
by the Italian Development Cooperation Agency and implemented with the support of
the volunteer work of Italian professionals, either physicians, nurses,
biologists and technicians. The intervention started in April 2016, was based
exclusively on training and coaching on site, that represent a significant
innovative approach, and led to a first autologous transplant in June 2016 and to
the first allogeneic transplant in October. At the time of reporting, 9 months
from the initiation of the project, 18 patients have been transplanted, 15 with
an autologous and 3 with an allogeneic graft. The center at the HCH represents
the first transplantation center in Kurdistan and the second in wide Iraq. We
conclude that international development cooperation may play an important role
also in the field of high-technology medicine, and contribute to improved local
centers capabilities through country to country scientific exchanges. The
methodology to realize this project is innovative, since HSCT experts are brought
as volunteers to the center(s) to be started, while traditionally it is the
opposite, i.e. the local professionals to be trained are brought to the
specialized center(s).
PMID- 28512561
TI - Bone Marrow Homing and Engraftment Defects of Human Hematopoietic Stem and
Progenitor Cells.
AB - Homing of hematopoietic stem cells (HSC) to their microenvironment niches in the
bone marrow is a complex process with a critical role in repopulation of the bone
marrow after transplantation. This active process allows for migration of HSC
from peripheral blood and their successful anchoring in bone marrow before
proliferation. The process of engraftment starts with the onset of proliferation
and must, therefore, be functionally dissociated from the former process. In this
overview, we analyze the characteristics of stem cells (SCs) with particular
emphasis on their plasticity and ability to find their way home to the bone
marrow. We also address the problem of graft failure which remains a significant
contributor to morbidity and mortality after allogeneic hematopoietic stem cell
transplantation (HSCT). Within this context, we discuss non-malignant and
malignant hematological disorders treated with reduced-intensity conditioning
regimens or grafts from human leukocyte antigen (HLA)-mismatched donors.
PMID- 28512563
TI - Acquired von Willebrand Syndrome Associated to Secondary IgM MGUS Emerging after
Autologous Stem Cell Transplantation for AL Amyloidosis.
AB - Acquired von Willebrand syndrome (AVWS) is a rare hemorrhagic disorder that
occurs in patients with no prior personal or family history of bleeding. Here, we
describe a case of AVWS occurring after autologous stem cell transplantation
(ASCT). Interestingly, AVWS developed after bortezomib-based induction and
conditioning regimens. Recent evidence suggests that the proximity of the
bortezomib therapy to the collection of stem cells with consequent depletion of
regulatory T cells after the conditioning regimen could explain some of the
unusual autoimmune complications reported in patients receiving bortezomib prior
to ASCT. In addition, this patient developed a secondary MGUS post-ASCT, which
may have also contributed to the AVWS. To the best of our knowledge, this is the
first case of post-ASCT AVWS reported. Prospective data is needed to better
elucidate the mechanisms by which these unusual complications occur in patients
receiving bortezomib prior to ASCT.
PMID- 28512562
TI - Morphologic Confounders and CD19 Negativity in a Case of Hairy Cell Leukemia.
AB - OBJECTIVES: We report a case of hairy cell leukemia (HCL) initially misdiagnosed
as plasma cell dyscrasia due to various clinical, morphological and
immunophenotypic confounders. METHODS AND RESULTS: In a patient diagnosed of
marrow plasmacytosis and serum monoclonal protein elsewhere and referred to our
hospital, morphological evaluation of bone marrow aspirate smears and trephine
biopsy, immunophenotyping, and molecular testing (BRAFV600E mutation) were done.
Clinically, the patient was asymptomatic; bone marrow revealed plasmacytosis,
mastocytosis, and lymphocytosis with a few "hairy" cells. Immunophenotyping
showed features of HCL with aberrant CD10 expression and a large subclone of
CD19neg cells. A diagnosis of HCL with reactive plasmacytosis and mast cell
hyperplasia was made and confirmed by immunophenotyping and molecular studies.
CONCLUSION: Hematopathologists must be aware of various confounding factors and
should judiciously use flow cytometric and molecular studies for attaining a
proper diagnosis of HCL. We also report a very rare immunophenotypic aberrancy
(CD 19 negativity) in HCL.
PMID- 28512565
TI - Developments in the structural science of materials.
AB - Recent developments in the structural science of materials and the growing power
of computational methods in this field are discussed.
PMID- 28512564
TI - Infections and Follicular Lymphoma: is there a Link?
AB - Several infectious agents appear to provide a proliferative signal -- "antigen
drive" - that could be implicated in the pathogenesis of various type of Non
Hodgkin Lymphoma (NHL). A classical model of the infection-driven
lymphoproliferative disorder is Helicobacter pylori-induced gastric MALT
lymphoma, where antibiotic therapy allows the eradication of both the infectious
agent and the clonal B-cell expansion. Following the footsteps of this example,
several retrospective studies have found a correlation with other pathogens and B
cell Lymphomas, adding new relevant information about pathogenesis and laying the
groundwork for chemotherapy-free treatments. Although no clear association has
been found between infectious agents and Follicular Lymphoma (FL), a growing
number of biological and clinical observations suggests the interaction of
physiological and pathological microbial populations also in this subtype of
lymphoma. In the last few years, epidemiological studies investigating the
association of known risk factors and FL found a potential correlation with viral
or bacterial infections; moreover, recent findings of the stimulation of FL
clones support the importance of microbial exposure to lymphomagenesis and
disease progression. In the following review we make an attempt to find tangible
evidence for a role of either physiological and pathological exogenous microbial
species in the pathogenesis of FL, and try to integrate the findings coming from
epidemiological, biological and interventional studies to define future novel
treatment and prevention strategies for FL.
PMID- 28512566
TI - Regulating thermosalient behaviour in three polymorphs.
AB - Three polymorphs of a di-chloro-N-salicylideneaniline derivative show visually
impressive jumping and sudden blasting behaviours on heating due to phase
transitions.
PMID- 28512567
TI - How many tricks can an old perovskite play?
AB - The ferroelectric-paraelectric transition in Li0.2Na0.8NbO3 is between two
extremely rare perovskite polytypes. How the unprecedented sequence of structures
was established shows that even old oxides can play new tricks.
PMID- 28512568
TI - Acemetacin cocrystal structures by powder X-ray diffraction.
AB - Cocrystals of acemetacin drug (ACM) with nicotinamide (NAM), p-aminobenzoic acid
(PABA), valerolactam (VLM) and 2-pyridone (2HP) were prepared by melt
crystallization and their X-ray crystal structures determined by high-resolution
powder X-ray diffraction. The powerful technique of structure determination from
powder data (SDPD) provided details of molecular packing and hydrogen bonding in
pharmaceutical cocrystals of acemetacin. ACM-NAM occurs in anhydrate and hydrate
forms, whereas the other structures crystallized in a single crystalline form.
The carboxylic acid group of ACM forms theacid-amide dimer three-point synthon
R32(9)R22(8)R32(9) with three different syn amides (VLM, 2HP and caprolactam).
The conformations of the ACM molecule observed in the crystal structures differ
mainly in the mutual orientation of chlorobenzene fragment and the neighboring
methyl group, being anti (type I) or syn (type II). ACM hydrate, ACM-NAM, ACM-NAM
hydrate and the piperazine salt of ACM exhibit the type I conformation, whereas
ACM polymorphs and other cocrystals adopt the ACM type II conformation. Hydrogen
bond interactions in all the crystal structures were quantified by calculating
their molecular electrostatic potential (MEP) surfaces. Hirshfeld surface
analysis of the cocrystal surfaces shows that about 50% of the contribution is
due to a combination of strong and weak O?H, N?H, Cl?H and C?H interactions. The
physicochemical properties of these cocrystals are under study.
PMID- 28512569
TI - Unprecedented phase transition sequence in the perovskite Li0.2Na0.8NbO3.
AB - The perovskite Li0.2Na0.8NbO3 is shown, by powder neutron diffraction, to display
a unique sequence of phase transitions at elevated temperature. The ambient
temperature polar phase (rhombohedral, space group R3c) transforms via a first
order transition to a polar tetragonal phase (space group P42mc) in the region
150-300 degrees C; these two phases correspond to Glazer tilt systems a-a-a- and
a+a+c-, respectively. At 500 degrees C a ferroelectric-paraelectric transition
takes place from P42mc to P42/nmc, retaining the a+a+c- tilt. Transformation to a
single-tilt system, a0a0c+ (space group P4/mbm), occurs at 750 degrees C, with
the final transition to the aristotype cubic phase at 850 degrees C. The P42mc
and P42/nmc phases have each been seen only once and twice each, respectively, in
perovskite crystallography, in each case in compositions prepared at high
pressure.
PMID- 28512570
TI - The structure of denisovite, a fibrous nanocrystalline polytypic disordered 'very
complex' silicate, studied by a synergistic multi-disciplinary approach employing
methods of electron crystallography and X-ray powder diffraction.
AB - Denisovite is a rare mineral occurring as aggregates of fibres typically 200-500
nm diameter. It was confirmed as a new mineral in 1984, but important facts about
its chemical formula, lattice parameters, symmetry and structure have remained
incompletely known since then. Recently obtained results from studies using
microprobe analysis, X-ray powder diffraction (XRPD), electron crystallography,
modelling and Rietveld refinement will be reported. The electron crystallography
methods include transmission electron microscopy (TEM), selected-area electron
diffraction (SAED), high-angle annular dark-field imaging (HAADF), high
resolution transmission electron microscopy (HRTEM), precession electron
diffraction (PED) and electron diffraction tomography (EDT). A structural model
of denisovite was developed from HAADF images and later completed on the basis of
quasi-kinematic EDT data by ab initio structure solution using direct methods and
least-squares refinement. The model was confirmed by Rietveld refinement. The
lattice parameters are a = 31.024 (1), b = 19.554 (1) and c = 7.1441 (5) A, beta
= 95.99 (3) degrees , V = 4310.1 (5) A3 and space group P12/a1. The structure
consists of three topologically distinct dreier silicate chains, viz. two
xonotlite-like dreier double chains, [Si6O17]10-, and a tubular loop-branched
dreier triple chain, [Si12O30]12-. The silicate chains occur between three walls
of edge-sharing (Ca,Na) octahedra. The chains of silicate tetrahedra and the
octahedra walls extend parallel to the z axis and form a layer parallel to (100).
Water molecules and K+ cations are located at the centre of the tubular silicate
chain. The latter also occupy positions close to the centres of eight-membered
rings in the silicate chains. The silicate chains are geometrically constrained
by neighbouring octahedra walls and present an ambiguity with respect to their z
position along these walls, with displacements between neighbouring layers being
either Deltaz = c/4 or -c/4. Such behaviour is typical for polytypic sequences
and leads to disorder along [100]. In fact, the diffraction pattern does not show
any sharp reflections with l odd, but continuous diffuse streaks parallel to a*
instead. Only reflections with l even are sharp. The diffuse scattering is caused
by (100) nano-lamellae separated by stacking faults and twin boundaries. The
structure can be described according to the order-disorder (OD) theory as a
stacking of layers parallel to (100).
PMID- 28512571
TI - Mechanochemical synthesis of N-salicylidene-aniline: thermosalient effect of
polymorphic crystals.
AB - Polymorphs of the dichloro derivative of N-salicylideneaniline exhibit mechanical
responses such as jumping (Forms I and III) and exploding (Form II) in its three
polymorphs. The molecules are connected via the amide N-H?O dimer synthon and C
Cl?O halogen bond in the three crystal structures. A fourth high-temperature Form
IV was confirmed by variable-temperature single-crystal X-ray diffraction at 180
degrees C. The behaviour of jumping exhibited by the polymorphic crystals of
Forms I and III is due to the layered sheet morphology and the transmission of
thermal stress in a single direction, compared with the corrugated sheet
structure of Form II such that heat dissipation is more isotropic causing
blasting. The role of weak C-Cl?O interactions in the thermal response of
molecular crystals is discussed.
PMID- 28512572
TI - Experimental strategies for imaging bioparticles with femtosecond hard X-ray
pulses.
AB - This study explores the capabilities of the Coherent X-ray Imaging Instrument at
the Linac Coherent Light Source to image small biological samples. The weak
signal from small samples puts a significant demand on the experiment.
Aerosolized Omono River virus particles of ~40 nm in diameter were injected into
the submicrometre X-ray focus at a reduced pressure. Diffraction patterns were
recorded on two area detectors. The statistical nature of the measurements from
many individual particles provided information about the intensity profile of the
X-ray beam, phase variations in the wavefront and the size distribution of the
injected particles. The results point to a wider than expected size distribution
(from ~35 to ~300 nm in diameter). This is likely to be owing to nonvolatile
contaminants from larger droplets during aerosolization and droplet evaporation.
The results suggest that the concentration of nonvolatile contaminants and the
ratio between the volumes of the initial droplet and the sample particles is
critical in such studies. The maximum beam intensity in the focus was found to be
1.9 * 1012 photons per um2 per pulse. The full-width of the focus at half-maximum
was estimated to be 500 nm (assuming 20% beamline transmission), and this width
is larger than expected. Under these conditions, the diffraction signal from a
sample-sized particle remained above the average background to a resolution of
4.25 nm. The results suggest that reducing the size of the initial droplets
during aerosolization is necessary to bring small particles into the scope of
detailed structural studies with X-ray lasers.
PMID- 28512573
TI - Photoreduction and validation of haem-ligand intermediate states in protein
crystals by in situ single-crystal spectroscopy and diffraction.
AB - Powerful synergies are available from the combination of multiple methods to
study proteins in the crystalline form. Spectroscopies which probe the same
region of the crystal from which X-ray crystal structures are determined can give
insights into redox, ligand and spin states to complement the information gained
from the electron-density maps. The correct assignment of crystal structures to
the correct protein redox and ligand states is essential to avoid the
misinterpretation of structural data. This is a particular concern for haem
proteins, which can occupy a wide range of redox states and are exquisitely
sensitive to becoming reduced by solvated electrons generated from interactions
of X-rays with water molecules in the crystal. Here, single-crystal spectroscopic
fingerprinting has been applied to investigate the laser photoreduction of ferric
haem in cytochrome c'. Furthermore, in situ X-ray-driven generation of haem
intermediates in crystals of the dye-decolourizing-type peroxidase A (DtpA) from
Streptomyces lividans is described.
PMID- 28512574
TI - Crystallographic and SAXS studies of S-adenosyl-l-homocysteine hydrolase from
Bradyrhizobium elkanii.
AB - S-Adenosyl-l-homocysteine hydrolase (SAHase) from the symbiotic bacterium
Bradyrhizobium elkanii (BeSAHase) was crystallized in four ligand complexes with
(i) mixed adenosine (Ado) and cordycepin (Cord; 3'-deoxyadenosine), (ii) adenine
(Ade), (iii) Ado and (iv) mixed 2'-deoxyadenosine (2'-dAdo) and Ade. The crystal
structures were solved at resolutions of 1.84, 1.95, 1.95 and 1.54 A,
respectively. Only the Ade complex crystallized with a dimer in the asymmetric
unit, while all of the other complexes formed a crystallographically independent
tetrameric assembly. In the Ado/Cord complex, adenosine is found in three
subunits while the fourth subunit has cordycepin bound in the active site. In the
Ade and Ado complexes only these ligand molecules are present in the active
sites. The 2'-dAdo/Ade complex has Ade bound in two subunits and 2'-dAdo bound in
the other two subunits. The BeSAHase fold adopted a closed conformation in the
complexes with Ado, Ade and 2'-dAdo, and a semi-open conformation when cordycepin
occupied the active site. An SAHase-specific molecular gate, consisting of
residues His342 and Phe343, behaves differently in the different complexes, but
there is no simple correlation with the ligand type. Additional small-angle X-ray
scattering (SAXS) experiments confirm the tetrameric state of the protein in
solution. The main conclusions from this work are (i) that the SAHase subunit
does not simply oscillate between two discrete conformational open/closed states
in correlation with the absence/presence of a ligand in the active site, but can
also assume an intermediate form for some ligands; (ii) that the shut/open state
of the molecular gate in the access channel to the active site is not correlated
in a simple way with the open/closed subunit conformation or empty/occupied
status of the active site, but that a variety of states are possible even for the
same ligand; (iii) that a cation (typically sodium) coordinated in an
intersubunit loop rigidifies a molecular hinge and thus stabilizes the closed
conformation; (iv) that BeSAHase in solution is a tetramer, consistent with the
model derived from crystallography.
PMID- 28512575
TI - New leads for fragment-based design of rhenium/technetium radiopharmaceutical
agents.
AB - Multiple possibilities for the coordination of fac-[Re(CO)3(H2O)3]+ to a protein
have been determined and include binding to Asp, Glu, Arg and His amino-acid
residues as well as to the C-terminal carboxylate in the vicinity of Leu and Pro.
The large number of rhenium metal complex binding sites that have been identified
on specific residues thereby allow increased target identification for the design
of future radiopharmaceuticals. The core experimental concept involved the use of
state-of-art tuneable synchrotron radiation at the Diamond Light Source to
optimize the rhenium anomalous dispersion signal to a large value (f'' of 12.1
electrons) at its LI absorption edge with a selected X-ray wavelength of 0.9763
A. At the Cu Kalpha X-ray wavelength (1.5418 A) the f'' for rhenium is 5.9
electrons. The expected peak-height increase owing to the optimization of the Re
f'' was therefore 2.1. This X-ray wavelength tuning methodology thereby showed
the lower occupancy rhenium binding sites as well as the occupancies of the
higher occupancy rhenium binding sites.
PMID- 28512577
TI - Genetic changes found in a distinct clade of Enterovirus D68 associated with
paralysis during the 2014 outbreak.
AB - Enterovirus D68 (EV-D68) caused a severe respiratory illness outbreak in the
United States in 2014. Reports of acute flaccid myelitis (AFM)/paralysis (AFP) in
several independent epidemiological clusters of children with detectable EV-D68
have raised concerns that genetic changes in EV-D68 could be causing increased
disease severity and neurological symptoms. To explore the potential link between
EV-D68 genetic variations and symptom changes, we performed a series of
comparative genomic analyses of EV-D68 2014 outbreak isolate sequences using data
and analytical tools in the Virus Pathogen Resource (ViPR; www.viprbrc.org). Our
results suggest that (1) three distinct lineages of EV-D68 were co-circulating in
2013 and 2014; (2) isolates associated with AFM/AFP belong to a single
phylogenetic subclade - B1; (3) the majority of isolates from the B1 subclade
have 21 unique substitutions that distinguish them from other isolates, including
amino acid substitutions in the VP1, VP2, and VP3 capsid proteins and the 3D RNA
dependent RNA polymerase, and nucleotide substitutions in the internal ribosome
entry sequence (IRES); (4) at 12 of these positions, B1 isolates carry the same
residues observed at equivalent positions in paralysis-causing enteroviruses,
including poliovirus, EV-D70 and EV-A71. Based on these results, we hypothesize
that unique B1 substitutions may be responsible for the apparent increased
incidence of neuropathology associated with the 2014 outbreak.
PMID- 28512576
TI - Applications of contact predictions to structural biology.
AB - Evolutionary pressure on residue interactions, intramolecular or intermolecular,
that are important for protein structure or function can lead to covariance
between the two positions. Recent methodological advances allow much more
accurate contact predictions to be derived from this evolutionary covariance
signal. The practical application of contact predictions has largely been
confined to structural bioinformatics, yet, as this work seeks to demonstrate,
the data can be of enormous value to the structural biologist working in X-ray
crystallo-graphy, cryo-EM or NMR. Integrative structural bioinformatics packages
such as Rosetta can already exploit contact predictions in a variety of ways. The
contribution of contact predictions begins at construct design, where structural
domains may need to be expressed separately and contact predictions can help to
predict domain limits. Structure solution by molecular replacement (MR) benefits
from contact predictions in diverse ways: in difficult cases, more accurate
search models can be constructed using ab initio modelling when predictions are
available, while intermolecular contact predictions can allow the construction of
larger, oligomeric search models. Furthermore, MR using supersecondary motifs or
large-scale screens against the PDB can exploit information, such as the parallel
or antiparallel nature of any beta-strand pairing in the target, that can be
inferred from contact predictions. Contact information will be particularly
valuable in the determination of lower resolution structures by helping to assign
sequence register. In large complexes, contact information may allow the identity
of a protein responsible for a certain region of density to be determined and
then assist in the orientation of an available model within that density. In NMR,
predicted contacts can provide long-range information to extend the upper size
limit of the technique in a manner analogous but complementary to experimental
methods. Finally, predicted contacts can distinguish between biologically
relevant interfaces and mere lattice contacts in a final crystal structure, and
have potential in the identification of functionally important regions and in
foreseeing the consequences of mutations.
PMID- 28512578
TI - Safety and Efficacy of Microinvasive Glaucoma Surgery.
AB - Microinvasive glaucoma surgery (MIGS) is emerging as a new therapeutic option for
glaucoma patients who wish to reduce their medication burden and avoid the
postoperative complications of conventional glaucoma filtration surgery. These
devices differ in terms of their efficacy and safety profile. Schlemm's canal
devices have the most favorable safety profile at the compromise of modest
efficacy, while subconjunctival and suprachoroidal devices are potentially more
effective at lowering the intraocular pressure at the expense of a higher rate of
complications. This review consolidates the latest evidence on the efficacy and
safety of the MIGS devices in clinical use and provides an overview on upcoming
devices which would likely also become viable treatment options in the near
future. These clinical data would assist a glaucoma surgeon in selecting the most
appropriate MIGS device for each patient based on the glaucoma severity and
patient expectations.
PMID- 28512579
TI - The Impact of Electronic Reading Devices on Reading Speed and Comfort in Patients
with Decreased Vision.
AB - Background/Aims. To evaluate the impact of back-illuminated and nonilluminated
electronic reading devices on reading speed and comfort in patients with
decreased vision. Methods. A prospective study involving a convenience sample of
167 patients at a single retina practice from January 2011 to December 2012.
Participants were asked to read five different excerpts on five different media
in a randomly assigned order. Media included a printed book at 12-point font
(12PF), iPad2 at 12PF, iPad2 at 18-point font (18PF), Kindle2 at 12PF, and
Kindle2 at 18PF. Reading speed in words per minute (WPM) and medium preference
were recorded and stratified by visual acuity (VA). Results. Mean reading speeds
in WPM: iPad2 at 18PF (217.0), iPad2 at 12PF (209.1), Kindle2 at 18PF (183.3),
Kindle2 at 12PF (177.7), and printed book at 12PF (176.8). Reading speed was
faster on back-illuminated media compared to nonilluminated media. Text
magnification minimized losses in reading performance with worsening patient VA.
The majority of participants preferred reading on the iPad2 at 18PF. Conclusions.
Back-illuminated devices may increase reading speed and comfort relative to
nonilluminated devices and printed text, particularly in patients with decreased
VA.
PMID- 28512581
TI - Refractive Lens Exchange Combined with Primary Posterior Vitrectorhexis in Highly
Myopic Patients.
AB - Purpose. To evaluate efficacy and safety of primary vitrectorhexis for posterior
capsulotomy in highly myopic patients undergoing refractive lens exchange.
Methods. The study is a prospective nonrandomized interventional study. The study
comprised 60 eyes of 60 myopic patients. All patients underwent refractive lens
exchange (RLE) and foldable IOL implantation combined with primary posterior
capsulotomy. We used a 23-gauge vitrectomy probe for the creation of the
posterior capsule opening. We followed the patients for one year. Results. During
surgery, the IOLs remained well centered in the capsular bag after creation of
the capsulotomy. Postoperatively, we did not report any complications related to
lens centration or changes in the posterior capsulotomy size. No eye required YAG
laser posterior capsulotomy and no cases of retinal detachment (RD) occurred
during the follow-up period. Conclusion. Primary posterior vitrectorhexis during
RLE is an efficient method in preventing the occurrence of posterior capsular
opacification (PCO) and the need for YAG laser posterior capsulotomy with its
possible complications.
PMID- 28512580
TI - High-Intensity Focused Ultrasound Circular Cyclocoagulation in Glaucoma: A Step
Forward for Cyclodestruction?
AB - The ciliary body ablation is still considered as a last resort treatment to
reduce the intraocular pressure (IOP) in uncontrolled glaucoma. Several ablation
techniques have been proposed over the years, all presenting a high rate of
complications, nonselectivity for the target organ, and unpredictable dose-effect
relationship. These drawbacks limited the application of cyclodestructive
procedures almost exclusively to refractory glaucoma. High-intensity focused
ultrasound (HIFU), proposed in the early 1980s and later abandoned because of the
complexity and side effects of the procedure, was recently reconsidered in a new
approach to destroy the ciliary body. Ultrasound circular cyclocoagulation (UC3),
by using miniaturized transducers embedded in a dedicated circular-shaped device,
permits to selectively treat the ciliary body in a one-step, computer-assisted,
and non-operator-dependent procedure. UC3 shows a high level of safety along with
a predictable and sustained IOP reduction in patients with refractory glaucoma.
Because of this, the indication of UC3 was recently extended also to naive-to
surgery patients, thus reconsidering the role and timing of ciliary body ablation
in the surgical management of glaucoma. This article provides a review of the
most used cycloablative techniques with particular attention to UC3, summarizing
the current knowledge about this procedure and future possible developments.
PMID- 28512582
TI - Factors Affecting Utilization of Voluntary HIV Counseling and Testing Services
among Teachers in Awi Zone, Northwest Ethiopia.
AB - HIV/AIDS affects the basic educational sector which is the most productive
segment of the population and vital to the creation of human capital. The loss of
skilled and experienced teachers due to the problem is increasingly compromising
the provision of quality education in most African countries. The study was
proposed to determine the magnitude of VCT utilization and assess contributing
factors that affect VCT service utilization among secondary school teachers in
Awi Zone. A cross-sectional study design was conducted among 588 participants in
2014. Self-administered questionnaire was used to collect data. Data was analyzed
using SPSS version 16, presented as frequencies and summary statistics, and
tested for presence of significant association with odds ratio at 95% CI. More
than half (53.6%) of study participants were tested for HIV. Those who had sexual
intercourse, had good knowledge about VCT, were divorced/widowed, were in the age
group of 20-29 years, and were married utilized VCT services two, three, four,
three, and two times better than their counterparts, respectively. Actions
targeting unmarried status, increase of educational level, and teachers with age
groups above 30 years are necessary to follow their counterparts to utilize VCT
service in order to save loss of teachers.
PMID- 28512583
TI - Role of Transbronchial Lung Cryobiopsies in Diffuse Parenchymal Lung Diseases:
Interest of a Sequential Approach.
AB - Background. Transbronchial lung cryobiopsies (TBLCs) are a promising diagnostic
tool in the setting of diffuse parenchymal lung diseases (DPLDs). However, no
comparison with surgical lung biopsy (SLB) in the same patient is available.
Methods. The diagnostic yield and safety data of TBLCs, as well as the result of
SLB performed after TBLCs, were analysed in a multicentric Belgian study. A SLB
was performed after TBLCs in absence of a definite pathological diagnosis or if a
NSIP pattern was observed without related condition identified following
multidisciplinary discussion. Results. Between April 2015 and November 2016, 30
patients were included. Frequent complications included pneumothorax (20%) and
bleeding (severe 7%, moderate 33%, and mild 53%). There was no mortality. The
overall diagnostic yield was 80%. A SLB was performed in six patients (three
without definite histological pattern and three with an NSIP). The surgical
biopsy changed the pathological diagnosis into a UIP pattern in five patients and
confirmed a NSIP pattern in one patient. Conclusion. TBLCs are useful in the
diagnostic work-up of DPLDs avoiding a SLB in 80% of the patients. However,
surgical biopsies, performed as a second step after TBLCs because of an
indefinite diagnosis or a NSIP pattern, provide additional information supporting
the interest of a sequential approach in these patients.
PMID- 28512584
TI - Neurorehabilitation: Neural Plasticity and Functional Recovery.
PMID- 28512586
TI - Cryoablation for Ventricular Tachycardia Originating from Anterior Papillary
Muscle of Left Ventricle Guided by Intracardiac Echocardiography.
AB - Papillary muscles (PMs) were reported to be origin of ventricular arrhythmia
(VA). Radiofrequency (RF) ablation was reported to be acutely effective in
eliminating VA. However, the recurrence rate is high. Recently, cryoablation
guided by intracardiac echocardiography, 3-dimensional mapping system, and image
integration was introduced as alternative strategy for this challenging ablation.
We present a case of ventricular tachycardia originating from anterior PM of left
ventricle treated by cryoablation guided only by intracardiac echocardiography.
PMID- 28512587
TI - Adenocarcinoma In Situ Arising from Brunner's Gland Treated by Endoscopic Mucosal
Resection.
AB - An 86-year-old Japanese man was presented to our hospital for further
investigation of duodenal adenocarcinoma. The tumor was endoscopically resected.
Pathological analysis revealed coexistence of gastric foveolar metaplasia and a
surrounding hyperplastic Brunner's gland, in addition to an adenocarcinoma
component. Immunostaining for MUC5AC and MUC6 confirmed the diagnosis of
adenocarcinoma in situ arising from Brunner's gland hyperplasia. This case
suggests that although detailed preoperative evaluation is required to determine
the depth of tumor invasion, endoscopic resection may be a promising option for
the treatment of adenocarcinomas arising from Brunner's gland hyperplasia.
PMID- 28512589
TI - A Case of Early Disseminated Neurological Lyme Disease Followed by Atypical
Cutaneous Manifestations.
AB - Lyme disease (LD) is a tick-borne illness caused by Borrelia burgdorferi sensu
stricto. An 80-year-old female from Pennsylvania, USA, presented to an outside
hospital with fever, confusion, lower extremity weakness, and stool incontinence.
CT head and MRI spine were unremarkable. An infectious work-up including lumbar
puncture was negative. She was transferred to our tertiary care hospital. Patient
was noted to have mild unilateral right-sided facial droop and a diffuse macular
rash throughout the body. She denied any outdoor activities, tick bites, or
previous rash. Intravenous ceftriaxone was started for suspected LD. The
patient's symptoms including facial droop resolved within 24 hours of antibiotic
therapy. Polymerase chain reaction of the blood, IgM ELISA, and IgM Western blot
testing for LD came back positive a few days after initiation of therapy. She was
treated for a total of 21 days for neurological LD with complete symptom
resolution. Not all patients have the classic "targetoid" EM rash on initial
presentation, rash could develop after neurological manifestations, and prompt
initiation of antibiotics without awaiting serology is paramount to making a
quick and a full recovery. There should be a high index of suspicion for early
disseminated LD, as presentations can be atypical.
PMID- 28512588
TI - Severe Aplastic Anemia following Parvovirus B19-Associated Acute Hepatitis.
AB - Human parvovirus (HPV) B19 is linked to a variety of clinical manifestations,
such as erythema infectiosum, nonimmune hydrops fetalis, and transient aplastic
anemia. Although a few cases have shown HPVB19 infection as a possible causative
agent for hepatitis-associated aplastic anemia (HAAA) in immunocompetent
patients, most reported cases of HAAA following transient hepatitis did not have
delayed remission. Here we report a rare case of severe aplastic anemia following
acute hepatitis with prolonged jaundice due to HPVB19 infection in a previously
healthy young male. Clinical laboratory examination assessed marked liver injury
and jaundice as well as peripheral pancytopenia, and bone marrow biopsy revealed
severe hypoplasia and fatty replacement. HPVB19 infection was diagnosed by enzyme
immunoassay with high titer of anti-HPVB19 immunoglobulin M antibodies.
Immunosuppressive therapy was initiated 2 months after the onset of acute
hepatitis when liver injury and jaundice were improved. Cyclosporine provided
partial remission after 2 months of medication without bone marrow
transplantation. Our case suggests that HPVB19 should be considered as a
hepatotropic virus and a cause of acquired aplastic anemia, including HAAA.
PMID- 28512585
TI - Understanding the Mechanisms of Recovery and/or Compensation following Injury.
AB - Injury due to stroke and traumatic brain injury result in significant long-term
effects upon behavioral functioning. One central question to rehabilitation
research is whether the nature of behavioral improvement observed is due to
recovery or the development of compensatory mechanisms. The nature of functional
improvement can be viewed from the perspective of behavioral changes or changes
in neuroanatomical plasticity that follows. Research suggests that these changes
correspond to each other in a bidirectional manner. Mechanisms surrounding
phenomena like neural plasticity may offer an opportunity to explain how
variables such as experience can impact improvement and influence the definition
of recovery. What is more, the intensity of the rehabilitative experiences may
influence the ability to recover function and support functional improvement of
behavior. All of this impacts how researchers, clinicians, and medical
professionals utilize rehabilitation.
PMID- 28512591
TI - Sporadic Insulinoma as a Rare Cause of Recurrent Hypoglycemia in Children.
AB - Insulinoma is a rare pancreatic tumor in children and adolescents. As a result of
insulin hypersecretion, signs and symptoms are more commonly consequences of the
pathophysiologic responses to hypoglycemia. According to rarity of this tumor in
children and nonspecificity of clinical presentations, diagnosis of insulinoma in
this group of patients is usually delayed. Early diagnosis is very important for
preventing neurologic damage. In this case report, we present the case of a 10
year-old boy with signs and symptoms of hypoglycemia and final diagnosis of
insulinoma.
PMID- 28512590
TI - Acute Bacterial Meningitis and Systemic Abscesses due to Streptococcus
dysgalactiae subsp. equisimilis Infection.
AB - Disseminated abscesses due to group G beta-hemolytic Streptococcus dysgalactiae
were observed in a 57-year-old cirrhotic patient with the skin being the putative
way of entry for the pathogen. S. dysgalactiae is a rare agent in human
infections responsible for acute pyogenic meningitis. The mortality rate
associated with S. dysgalactiae bacteraemia and meningitis may be as high as 50%,
particularly in the presence of endocarditis or brain abscesses. In our patient,
main sites of infections were meningitis and ventriculitis, spondylodiscitis,
septic arthritis, and soft-tissue infections. In contrast, no endocarditis was
evidenced. Cirrhosis-related immune suppression was considered as a
pathophysiological cofactor for the condition. Fortunately, clinical status
improved after long-term (3 months) antimicrobial therapy.
PMID- 28512593
TI - Electrochemical Determination of Caffeine Content in Ethiopian Coffee Samples
Using Lignin Modified Glassy Carbon Electrode.
AB - Lignin film was deposited at the surface of glassy carbon electrode
potentiostatically. In contrast to the unmodified glassy carbon electrode, an
oxidative peak with an improved current and overpotential for caffeine at
modified electrode showed catalytic activity of the modifier towards oxidation of
caffeine. Linear dependence of peak current on caffeine concentration in the
range 6 * 10-6 to 100 * 10-6 mol L-1 with determination coefficient and method
detection limit (LoD = 3 s/slope) of 0.99925 and 8.37 * 10-7 mol L-1,
respectively, supplemented by recovery results of 93.79-102.17% validated the
developed method. An attempt was made to determine the caffeine content of
aqueous coffee extracts of Ethiopian coffees grown in four coffee cultivating
localities (Wonbera, Wolega, Finoteselam, and Zegie) and hence to evaluate the
correlation between users preference and caffeine content. In agreement with
reported works, caffeine contents (w/w%) of 0.164 in Wonbera coffee; 0.134 in
Wolega coffee; 0.097 in Finoteselam coffee; and 0.089 in Zegie coffee were
detected confirming the applicability of the developed method for determination
of caffeine in a complex matrix environment. The result indicated that users'
highest preference for Wonbera and least preference for Zegie cultivated coffees
are in agreement with the caffeine content.
PMID- 28512592
TI - The Relationship between Body Mass Index and the Severity of Coronary Artery
Disease in Patients Referred for Coronary Angiography.
AB - Background and Aim. Obesity is associated with an increased risk of
cardiovascular disease and may be associated with more severe coronary artery
disease (CAD); however, the relationship between body mass index [BMI (kg/m2)]
and CAD severity is uncertain and debatable. The aim of this study was to examine
the relationship between BMI and angiographic severity of CAD. Methods. Duke
Jeopardy Score (DJS), a prognostic tool predictive of 1-year mortality in CAD,
was assigned to angiographic data of patients >=18 years of age (N = 8,079).
Patients were grouped into 3 BMI categories: normal (18.5-24.9 kg/m2), overweight
(25.0-29.9 kg/m2), and obese (>=30 kg/m2); and multivariable adjusted hazard
ratios for 1-year all-cause and cardiac-specific mortality were calculated.
Results. Cardiac risk factor prevalence (e.g., diabetes, hypertension, and
hyperlipidemia) significantly increased with increasing BMI. Unadjusted all-cause
and cardiac-specific 1-year mortality tended to rise with incremental increases
in DJS, with the exception of DJS 6 (p < 0.001). After adjusting for potential
confounders, no significant association of BMI and all-cause (HR 0.70, 95% CI .48
1.02) or cardiac-specific (HR 1.11, 95% CI .64-1.92) mortality was found.
Conclusions. This study failed to detect an association of BMI with 1-year all
cause or cardiac-specific mortality after adjustment for potential confounding
variables.
PMID- 28512594
TI - Rapid Determination of Six Low Molecular Carbonyl Compounds in Tobacco Smoke by
the APCI-MS/MS Coupled to Data Mining.
AB - A simple method was established for the rapid determination of low molecular
carbonyl compounds by the combination of atmospheric pressure chemical ionization
tandem mass spectrometry (APCI-MS/MS) and data mining. The ionization was carried
out in positive mode, and six low molecular carbonyl compounds of acrolein,
acetone, propionaldehyde, crotonaldehyde, butanone, and butyraldehyde were
analyzed by both full scan mode and daughter scan mode. To overcome the
quantitative difficulties from isomer of acetone/propionaldehyde and
butanone/butyraldehyde, the quantitation procedure was performed with the
characteristic ion of [CH3O]+ under CID energy of 5 and 15 eV. Subsequently, the
established method was successfully applied to analysis of six low molecular
carbonyl compounds in tobacco smoke with analytical period less than four
minutes. The contents of acrolein, acetone, propionaldehyde, crotonaldehyde,
butanone, and butyraldehyde for a cigarette were about 63 +/- 5.8, 325 +/- 82, 55
+/- 9.7, 11 +/- 1.4, 67 +/- 5.9, and 12 +/- 1.8 MUg/cig, respectively. The
experimental results indicated that the established method had the potential
application in rapid determination of low molecular carbonyl compounds.
PMID- 28512596
TI - In vitro screening for protein tyrosine phosphatase 1B and dipeptidyl peptidase
IV inhibitors from selected Nigerian medicinal plants.
AB - BACKGROUND/AIM: Protein tyrosine phosphatase 1B (PTP 1B) and dipeptidyl peptidase
IV (DPP IV) have been identified as one of the drug targets for the treatment of
Type-2 diabetes. This study was designed to screen for PTP 1B and DPP-IV
inhibitors from some Nigerian medicinal plants. MATERIALS AND METHODS: PTP 1B and
DPP-IV drug discovery kits from Enzo Life Sciences were used to investigate in
vitro inhibitory effect of crude methanolic extract of 10 plants; Mangifera
indica, Moringa oleifera, Acacia nilotica, Arachis hypogaea, Senna nigricans,
Azadirachta indica, Calotropis procera, Leptadenia hastata, Ziziphus mauritiana,
and Solanum incanum. RESULTS: The results indicated PTP IB inhibition by S.
nigricans (68.2 +/- 2.29%), A. indica (67.4 +/- 2.80%), A. hypogaea (57.2 +/-
2.50%), A. nilotica (55.1 +/- 2.19%), and M. oleifera (41.2 +/- 1.87%) were
significantly (P < 0.05) higher as compared with standard inhibitor, sumarin
while that of L. hastata (18.1 +/- 2.00%) was significantly lower as compared
with sumarin. The PTB 1B inhibition by M. indica (31.5 +/- 1.90%) was not
significantly (P > 0.05) different from that of sumarin. The DPP-IV inhibition by
S. incanum (68.1 +/- 2.71%) was significantly higher as compared with a known
inhibitor, P32/98. S. nigrican (57.0+/-1.91%), Z. mauritiana (56.6+/-2.01%), A.
hypogaea (51.0+/-1.30%), M. indica (44.6 +/- 2.40%), C. procera (36.2 +/- 2.00%),
A. nilotica (35.4 +/- 2.10%), and A. indica (33.6 +/- 1.50%) show significantly
(P < 0.05) lower inhibitions toward DPP-IV. CONCLUSION: The work demonstrated
that these plant materials could serve as sources of lead compounds in the
development of anti-diabetic agent(s) targeting PTP 1B and/or DPP-IV.
PMID- 28512595
TI - Reassessment of the polar fraction of Stachys alopecuros (L.) Benth. subsp.
divulsa (Ten.) Grande (Lamiaceae) from the Monti Sibillini National Park: A
potential source of bioactive compounds.
AB - BACKGROUND: The phytochemical analysis of Stachys alopecuros subsp. divulsa, an
endemic Italian species, has been recently reported and has showed the presence
of 8-O-acetylharpagide (2), harpagide (3), allobetonicoside (4), and 4c-O
galactopyranosyl-teuhircoside (5). In this paper, an in deep study of its
glycosidic fraction with the aim to widen the knowledge on its secondary
metabolites content is reported. MATERIALS AND METHODS: Chromatographic
techniques were used for the isolation of constituents while spectroscopic and
spectrometric techniques were applied for the structures elucidation. RESULTS:
Besides the known constituents, all of them reconfirmed, ajugoside (1), reptoside
(6) and 6-O-acetyl-ajugol (7) were also identified among the iridoids while the
phenolic components resulted to be chlorogenic acid (8), b-arbutin (9),
verbascoside (10), and stachysoside A (11), instead. CONCLUSION: The iridoid
pattern of S. alopecuros subsp. divulsa has been expanded with the identification
of not previously reported compounds as well as for the phenolic fraction. Except
for the reconfirmed verbascoside (10), the other phenolic compounds were
recognized for the first time in the studied species. The complete NMR assignment
of compound (1) by means of bidimensional techniques is reported, and both the
chemotaxonomic and pharmacological relevance of the isolated compounds is largely
discussed.
PMID- 28512597
TI - Documentation of ethnomedicinal information and antimicrobial validation of
Thespesia populnea used by Yanadi tribe of Ganugapenta village, Chittoor
district, Andhra Pradesh, India.
AB - AIM: This study aimed to document the traditional knowledge of medicinal plants
and antimicrobial validation of Thespesia populnea used by Yanadi tribe of
Chittoor district, Andhra Pradesh, India. MATERIALS AND METHODS: The study was
mainly focused on documentation of medicinal plants used by Yanadi tribe to treat
different diseases with a standard questionnaire. These plants were cross-checked
in Dr. Dukes Database and available literature to know the significance of this
tribe on medicinal knowledge. Among the documented plants, T. populnea was
selected for antimicrobial activity with disc diffusion assay. RESULTS: Among the
documented medicinal plants, herbs were the most utilized plants, followed by
leaf part of the plants; paste form of medicinal preparation was the dominant one
among the mode of preparations and oral administration was generally followed by
this tribe. When checked these plants in Dr. Duke's Phytochemical and
Ethnobotanical Database most of the medicinal plants were matched at least one
medicinal use and most of them were correlated with existing literature. In
antimicrobial activity, the microbial pathogens Klebsiella pneumonia among
bacteria and Rhizopus arrhizus among fungi were most susceptible to methanol
extract of T. populnea. CONCLUSION: From this study, we conclude that the
preparation and dosage of the medicines by Yanadi tribe of this area is unique
and the correlation of medicinal data with Duke's Database and existing
literature reveals high medicinal significance of claimed data of this tribe and
potential inhibitory activity of T. populnea could be studied further to isolate
effective antimicrobial agents.
PMID- 28512598
TI - Phytochemical screening and study of antioxidant, antimicrobial, antidiabetic,
anti-inflammatory and analgesic activities of extracts from stem wood of
Pterocarpus marsupium Roxburgh.
AB - AIMS: The main aims of the study were to evaluate the phytochemical constituents
and to study the antioxidant, antimicrobial, antidiabetic, anti-inflammatory, and
analgesic activities of extracts from stem wood of Pterocarpus marsupium.
MATERIALS AND METHODS: Ethanol, acetone and isopropyl alcohol (IPA) (1:1)
extracts of stem wood of P. marsupium were subjected to phytochemical screening
and analysis of biological activities from August 2015 to January 2016. The
antioxidant assay was carried out using 2, 2-diphenyl-1-picrylhydrazyl scavenging
method, antimicrobial activity testing by cup diffusion method, antidiabetic test
evaluation by oral glucose tolerance test in mice, anti-inflammatory effect was
evaluated by hind paw edema method in mice and analgesic test evaluation by a
chemical writhing method in mice. RESULTS: The results of the study revealed that
P. marsupium is a source of various phytoconstituents such as alkaloids,
glycosides, saponins, tannins, proteins, carbohydrates, cardiac glycosides,
flavonoids, and terpenoids. Both the acetone and IPA extract as well as the
ethanol extract of stem wood of P. marsupium exhibited a dose-dependent
antioxidant activity. Acetone and IPA extract showed antibacterial activity
against Gram-positive bacteria, while the ethanolic extract was found to possess
antidiabetic activity. The antidiabetic activity of the extract was found to be
time and dose-dependent. Similarly, the acetone and IPA extract was found to have
anti-inflammatory activity, which was also time and dose-dependent. Furthermore,
the ethanolic extract showed analgesic activity, which was dose-dependent. The
ethanolic extract was found to be nontoxic. CONCLUSIONS: Thus, this study laid
sufficient background for the further research on extracts from stem wood of P.
marsupium for identification, subsequent purification and isolation of compounds
having antibacterial, antidiabetic, anti-inflammatory, and analgesic activities.
PMID- 28512599
TI - Effect of Trichilia monadelpha (Meliaceae) extracts on bone histomorphology in
complete Freund's adjuvant-induced arthritis.
AB - AIM: This study aimed to assess the effect of petroleum ether extract (PEE),
ethyl acetate extract (EthE), and ethanol extract (EAE) of Trichilia monadelpha
stem bark on bone histomorphology in arthritis. METHODS: Percentage inhibition of
edema and arthritic scores in complete Freund's adjuvant-induced (0.1 ml of 5
mg/ml1 of heat-killed Mycobacterium tuberculosis in paraffin oil-injected
subplantar into the right hind paw) arthritic Sprague-Dawley rats treated with
PEE, EthE, or EAE (10,30, and 100 mg/kg1, respectively), dexamethasone (0.3-3.0
mg/kg1), or methotrexate (0.1-1.0 mg/kg1) over a 28-day period were estimated.
Rat paws were radiographed and scored. Body weights were taken and paw tissues
were harvested for histopathological studies. RESULTS: The extracts significantly
(P <= 0.01-0.0001) and dose dependently reduced the polyarthritic phase of
arthritis. EAE and PEE significantly (P <= 0.01-0.0001) minimized edema spread
from acute arthritic phase (days 0-10) to polyarthritic phase (days 10-28). EthE
improved which deteriorated body weight in arthritis. All extracts significantly
(P <= 0.05-0.01) improved arthritic score; reducing erythema, swelling and joint
rigidity, and also significantly (P <= 0.05-0.01) reduced hyperplasia, pannus
formation, and exudation of inflammatory cells into synovial spaces. CONCLUSION:
The stem bark extracts of T. monadelpha reduce bone tissue damage and resorption
associated with adjuvant-induced arthritis, hence could be useful in managing
arthritis in humans.
PMID- 28512600
TI - A synergistic effect of artocarpanone from Artocarpus heterophyllus L. (Moraceae)
on the antibacterial activity of selected antibiotics and cell membrane
permeability.
AB - AIM/BACKGROUNDS: Artocarpanone isolated from Artocarpus heterophyllus L.
(Moraceae) exhibits antibacterial activity. The present study investigated
synergistic activity between artocarpanone and tetracycline, ampicillin, and
norfloxacin, respectively, against methicillin-resistant Staphylococcus aureus
(MRSA), Pseudomonas aeruginosa, and Escherichia coli. MATERIALS AND METHODS: A
broth microdilution method was used for evaluating antibacterial susceptibility.
Synergistic effects were identified using a checkerboard method, and a bacterial
cell membrane disruption was investigated by assay of released 260 nm absorbing
materials following bacteriolysis. RESULTS AND DISCUSSION: Artocarpanone
exhibited weak antibacterial activity against MRSA and P. aeruginosa with minimum
inhibitory concentrations values of 125 and 500 MUg/mL, respectively. However,
the compound showed strong antibacterial activity against E. coli (7.8 MUg/mL).
The interaction between artocarpanone and all tested antibiotics revealed
indifference and additive effects against P. aeruginosa and E. coli (fractional
inhibitory concentration index [FICI] values of 0.75-1.25). The combination of
artocarpanone (31.2 MUg/mL) and norfloxacin (3.9 MUg/mL) resulted in synergistic
antibacterial activity against MRSA, with an FICI of 0.28, while the interaction
between artocarpanone and tetracycline, and ampicillin showed an additive effect,
with an FICI value of 0.5. A time-kill assay also indicated that artocarpanone
had a synergistic effect on the antibacterial activity of norfloxacin. In
addition, the combination of artocarpanone and norfloxacin altered the membrane
permeability of MRSA. CONCLUSION: These findings suggest that artocarpanone may
be used to enhance the antibacterial activity of norfloxacin against MRSA.
PMID- 28512601
TI - Anti-nociceptive and anti-inflammatory potentials of Vernoniaamygdalina leaf
extract via reductions of leucocyte migration and lipid peroxidation.
AB - BACKGROUND: Vernonia amygdalina is well known as a medicinal plant in folk
medicine as antidiabetic, anthelmintic, antimalarial, laxative/purgative, and
expectorant among others. AIM: This study was conducted to investigate the
antinociceptive and anti-inflammatory effects of V. amygdalina. MATERIALS AND
METHODS: Methanol extract of V. amygdalina leaf (MEVA) was evaluated for
antinociceptive effect and possible mechanisms of action in the presence of
naloxone (1 mg/kg), atropine (2 mg/kg), and prazosin (1 mg/kg) using acetic acid
writhing test in mice. The anti-inflammatory effect was evaluated in carrageenan
hind paw edema and carrageenan air pouch models. Protein concentration,
malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) assays
were carried out for its antioxidative activities in inflammation. Hematoxylin
and eosin staining was used to assess the level of inflammation. RESULTS: From
the acetic acid writhing test results, MEVA (50,100 mg/kg) showed significant
antinociceptive effect. Naloxone, atropine and prazosin did not significantly
reverse the antinociceptive effect of MEVA (50 mg/kg). MEVA (50, 100, and 200
mg/kg) showed dose-dependent inhibition of edema (41.4, 63.0, and 68.6%) at 4 h
post-carrageenan injection. In the carrageenan air pouch model, MEVA (200 mg/kg)
significantly (P < 0.05) reduced infiltrating leukocytes, protein concentration
and MDA levels, while GSH and SOD were unaffected. The histological study showed
a reduction in the infiltration of inflammatory cells in MEVA-treated groups.
CONCLUSION: V. amygdalina showed antinociceptive activity and anti-inflammatory
effect via reductions of leukocyte migration and lipid peroxidation.
PMID- 28512603
TI - Bactericidal activity of herbal volatile oil extracts against multidrug-resistant
Acinetobacter baumannii.
AB - AIM: The aim of the study is to investigate the antibacterial activity of 10
volatile oils extracted from medicinal plants, including galangal (Alpinia
galanga Linn.), ginger (Zingiber officinale), plai (Zingiber cassumunar Roxb.),
lime (Citrus aurantifolia), kaffir lime (Citrus hystrix DC.), sweet basil (Ocimum
basilicum Linn.), tree basil (Ocimum gratissimum), lemongrass (Cymbopogon
citratus DC.), clove (Syzygium aromaticum), and cinnamon (Cinnamomum verum)
against four standard strains of Staphylococcus aureus, Escherichia coli,
Pseudomonas aeruginosa, Acinetobacter baumannii, and 30 clinical isolates of
multidrug-resistant A. baumannii (MDR-A. baumannii). MATERIALS AND METHODS: Agar
diffusion, minimum inhibitory concentration, and minimum bactericidal
concentration (MBC) were employed for the determination of bactericidal activity
of water distilled medicinal plants. Tea tree oil (Melaleuca alternifolia) was
used as positive control in this study. RESULTS: The results indicated the
volatile oil extracted from cinnamon exhibited potent antibacterial activity
against the most common human pathogens, S. aureus, E. coli, P. aeruginosa, and
A. baumannii. Most of volatile oil extracts were less effective against non
fermentative bacteria, P. aeruginosa. In addition, volatile oil extracted from
cinnamon, clove, and tree basil possessed potent bactericidal activity against
MDR-A. baumannii with MBC90 of 0.5, 1, and 2 mg/mL, respectively. CONCLUSIONS:
The volatile oil extracts would be useful as alternative natural product for the
treatment of the most common human pathogens and MDR-A. baumannii infections.
PMID- 28512604
TI - Traditional dentistry knowledge among Serbs in several Balkan countries.
AB - BACKGROUND/AIM: There are still unrevealed treasures of traditional dental
medicine, that is, the reason to investigate and present various ways in
treatment of oral and orofacial tissues, as well as magic and religious elements
involved in representative areas among Serbs. MATERIALS AND METHODS: Information
was collected from the elderly non-professional folk dentists and herbalists with
the additional help of local physicians and dentists that was done through
questionnaire and personal interviews. RESULTS: Classified and prepared material
consists of total 1038 inquiry sheets. The 41 data were averagely obtained by
inquiry form, i.e. 41,984 information for the whole research. The most voluminous
was the group of 64 recipes, including 39 for gums diseases and 25 for toothache,
while only seven ones were mentioned for magic way of treatment. Among them, 18
prescriptions were of nonherbal origin. The study revealed 84 herbal original
prescriptions, including 67 plant species (29 families) including local name,
synonyms, and preparation mode. Traditional healers used predominantly herbal
recipes to treat painful tooth, gum disease, blisters - herpetic ulcers/lips and
mouth/, stomatitis/painful mouth, ptyalismus/, maxillary sinusitis, bad breath,
teeth cleaning and bleaching. Very few methods of treatment appeared as
inadequate (magical practice), whereas majority were noted as beneficial ones
(herbal medicine). Still many people in distant nonurban areas use various plant
recipes, especially as the first aid in oral disease healing. CONCLUSIONS: The
significance of plants obtained from unpolluted areas, whose active ingredients
have not yet been used in dental pharmaceutics, should be further investigated in
the future.
PMID- 28512602
TI - Bio-efficacy of medicinal plants used for the management of diabetes mellitus in
Gabon: An ethnopharmacological approach.
AB - BACKGROUND/AIM: People suffering of diabetes increased significantly worldwide.
Population, in Sub-Saharan Africa and mainly in Gabon, rely on medicinal plants
to manage diabetes, as well in rural as in urban areas. This study aimed to
survey a wide range of Gabonese plants for their antidiabetic activity. MATERIALS
AND METHODS: This study focused on the identification of medicinal plants used in
the local treatment of diabetes mellitus. Ethnobotanical investigations were
carried out in rural and urban areas of three provinces of Gabon using a semi
structured interview. RESULTS: About 50 plant species belonging to 31 families
and 50 genera were recorded, a majority of which have been documented previously
to have medicinal properties. Most have documented antidiabetic properties with
characterized therapeutic chemical compounds. Of the plant parts used for
treatment, stem barks were employed most frequently (50%), followed by leaves
(26%); the remaining 24% comprised roots, fibers, fruit, bulbs, flowers, rhizom,
skin, and stem. Regarding the mode of preparation, decoction was the most widely
used (58%), followed by maceration (18%) and infusion (14%). Almost all the plant
products were administered orally (98%). CONCLUSIONS: Taken in concert, this
study highlights the possibility of exploiting traditional knowledge of specific
medicinal plants for the inexpensive treatment and management of diabetes.
PMID- 28512605
TI - Toxicity status and antiulcerative potential of Sansevieria trifasciata leaf
extract in Wistar rats.
AB - AIMS: The lethal dose 50% (LD50) and antiulcerative potentials of Sansevieria
trifasciata (ST) leaf extract were investigated. MATERIALS AND METHODS: LD50 was
determined through two routes of administration (intraperitoneal [i.p] and oral
[p.o]) using the method of Lorke. The antiulcerative activity was evaluated in
indomethacin-induced ulcer model (40 mg/kg body weight [BW], i.p, single dose)
against a reference drug, cimetidine (100 mg/kg BW, p.o). ST was assessed at two
different doses (200 and 400 mg/kg BW, p.o). Treatments were done twice daily at
8 h interval for 7 days before indomethacin administration. RESULTS: The i.p LD50
was determined as 774.60 mg/kg BW and oral administration of the extract at
18,000 mg/kg BW dosage did not cause any negative behavioral changes in the
animals, and no mortality was recorded after 24 h of the experiment. ST-pre
treated animals showed some improvement against indomethacin-induced ulceration.
The extract curtailed indomethacin-induced reduction in gastric volume (36.1%),
free acidity (55.3%), total acidity (35.6%) while minimizing the increase in pH
by 13.3%. Moreover, the extract showed 17.92% and 14.96% ulcer protective ability
at 200 and 400 mg/kg BW, respectively. The phytochemical analysis of ST extract
revealed the presence of phytoconstituents such as glycosides, saponins,
flavonoids, terpenoids, alkaloids, tannins, anthraquinone, and glycosides.
CONCLUSIONS: ST apparently has a promising antiulcerative potential, and is safe
for use in folk medicine. This valuable medicinal property is probably due to the
array of important phytochemicals contained in the plant as observed in this
study. However, a further study involving bioassay-guided identification of the
main antiulcerative compound in ST is required to establish the use of the plant
as a viable antiulcerative agent.
PMID- 28512606
TI - Antimicrobial activity of Nigerian medicinal plants.
AB - Antimicrobial resistance (AMR) is currently one of the major threats facing
mankind. The emergence and rapid spread of multi- and pan-drug-resistant
organisms (such as vancomycin-, methicillin-, extended-spectrum beta-lactam-,
carbapenem- and colistin-resistant organisms) has put the world in a dilemma. The
health and economic burden associated with AMR on a global scale are dreadful.
Available antimicrobials have been misused and are almost ineffective with some
of these drugs associated with dangerous side effects in some individuals.
Development of new, effective, and safe antimicrobials is one of the ways by
which AMR burden can be reduced. The rate at which microorganisms develop AMR
mechanisms outpaces the rate at which new antimicrobials are being developed.
Medicinal plants are potential sources of new antimicrobial molecules. There is
renewed interest in antimicrobial activities of phytochemicals. Nigeria boasts of
a huge heritage of medicinal plants and there is avalanche of researches that
have been undertaken to screen antimicrobial activities of these plants.
Scientific compilation of these studies could provide useful information on the
antimicrobial properties of the plants. This information can be useful in the
development of new antimicrobial drugs. This paper reviews antimicrobial
researches that have been undertaken on Nigerian medicinal plants.
PMID- 23868168
TI - An Algorithm for Calculating the Probability of Classes of Data Patterns on a
Genealogy.
AB - Felsenstein's pruning algorithm allows one to calculate the probability of any
particular data pattern arising on a phylogeny given a model of character
evolution. Here we present a similar dynamic programming algorithm. Our algorithm
treats the tree and model as known. The algorithm makes it feasible to calculate
the probability that a randomly selected character will be a member of a
particular class of character patterns. Specifically, we are interested in
binning patterns by the number of parsimony steps and the set of states observed
at the tips of the tree. This algorithm was developed to expand the range of data
set sizes that can be used with Waddell et al.'s marginal testing approach for
assessing the adequacy of a model. The algorithms introduced can also be used in
likelihood calculations which correct for ascertainment biases. For example,
Lewis introduced an Mkv model which corrects for the lack of constant sites. The
probability of a constant pattern arising can be calculated using the algorithm
that we present, or by enumerating all possible constant patterns and calculating
the probability of each one. Because the number of constant data patterns is
small, both methods are efficient. However, elaborations of the Mkv model (such
as those in Nylander et al) require calculating the probability of parsimony
uninformative patterns arising. For large trees and characters with many possible
character states, the number of possible parismony-uninformative patterns is
immense. In these cases, the algorithms introduced here will be more efficient.
The algorithm has been implemented in open source software written in C++.
PMID- 24678439
TI - The Role of Veterans Affairs in Emergency Management: A Systematic Literature
Review.
AB - The Department of Veterans Affairs (VA) is a key player in emergency management
for both veterans and civilians. Unfortunately, limited evidence-based research
findings exist regarding the role and experience of VA during disasters. The
present study is a systematic literature review of 41 published, peer-reviewed
articles regarding VA and emergency management. Trained researchers utilized a
data abstraction tool and conducted a qualitative content analysis. A description
of article characteristics include methodology, phase of emergency management
addressed in the research, and study design. Five topic categories emerged from
the review including effects of disaster on mental health status and services
use, effects of disaster on general health services use, patient tracking,
evacuation, and disaster planning/preparation. Findings were used to generate
suggestions for future research.
PMID- 24818064
TI - A Prospective Study of the Outcome of Patients with Limb Trauma following the
Haitian Earthquake in 2010 at One- and Two- Year (The SuTra2 Study).
AB - Background Severe limb trauma is common in earthquake survivors. Overall medium
term outcomes and patient-perceived outcomes are poorly documented. Methods and
Findings The prospective study SuTra2 assessed the functional and socio-economic
status of a cohort of patients undergoing surgery for limb injury resulting in
amputation (A) or limb preservation (LP) one year and two years after the 2010
Haiti earthquake. 305 patients [A: n=199 (65%), LP: n=106 (35%)] were evaluated.
Their characteristics were: 57% female; mean age 31 years; 74% of principal
injuries involved the lower limb; 46% of patients had an additional severe
injury; 60% had fractures, of which two-thirds were compound or associated with
severe soft tissue damage; 15% of amputations were traumatic. At 2 years, 51% of
patients were satisfied with the functional outcome (A: 52%, LP: 49%, ns).
Comparison with the 1-year status indicates a worsening of the perceived
functional status, significantly more pronounced in amputees, and an increase in
pain complaints, mainly in amputees (62% and 80% of pain in overall population at
1- and 2-year respectively). Twenty eight percent (28%) of LP and 66% of A
considered themselves as "cured". 100% of LP and 79% of A would have chosen a
conservative approach if an amputation was medically avoidable. Two years after
the earthquake, 23.5 % of patients were still living in a tent, 30% were working,
and 25.5% needed ongoing surgical management. Conclusions Only half the patients
with severe limb injuries, whether managed with amputation or limb preservation,
deemed their functional status satisfactory at 2 years. The patients'
perspective, clearly favors limb conservative management whenever possible.
Prolonged care and rehabilitation are needed to optimize the outcome for
earthquake survivors with limb injuries. Humanitarian respondents to catastrophes
have professional and ethical obligations to provide optimal immediate care and
ensure scrupulous attention to long-term management. Keywords Haiti earthquake,
limb injury, two-year outcome, patients' perspective, amputation, limb salvage.
PMID- 28512610
TI - Melanoma Is Skin Deep: A 3D Reconstruction Technique for Computerized Dermoscopic
Skin Lesion Classification.
AB - Melanoma mortality rates are the highest amongst skin cancer patients. Melanoma
is life threating when it grows beyond the dermis of the skin. Hence, depth is an
important factor to diagnose melanoma. This paper introduces a non-invasive
computerized dermoscopy system that considers the estimated depth of skin lesions
for diagnosis. A 3-D skin lesion reconstruction technique using the estimated
depth obtained from regular dermoscopic images is presented. On basis of the 3-D
reconstruction, depth and 3-D shape features are extracted. In addition to 3-D
features, regular color, texture, and 2-D shape features are also extracted.
Feature extraction is critical to achieve accurate results. Apart from melanoma,
in-situ melanoma the proposed system is designed to diagnose basal cell
carcinoma, blue nevus, dermatofibroma, haemangioma, seborrhoeic keratosis, and
normal mole lesions. For experimental evaluations, the PH2, ISIC: Melanoma
Project, and ATLAS dermoscopy data sets is considered. Different feature set
combinations is considered and performance is evaluated. Significant performance
improvement is reported the post inclusion of estimated depth and 3-D features.
The good classification scores of sensitivity = 96%, specificity = 97% on PH2
data set and sensitivity = 98%, specificity = 99% on the ATLAS data set is
achieved. Experiments conducted to estimate tumor depth from 3-D lesion
reconstruction is presented. Experimental results achieved prove that the
proposed computerized dermoscopy system is efficient and can be used to diagnose
varied skin lesion dermoscopy images.
PMID- 28512612
TI - Review of Cranioplasty after Decompressive Craniectomy.
AB - Cranioplasty is an in evitable operation conducted after decompressive
craniectomy (DC). The primary goals of cranioplasty after DC are to protect the
brain, achieve a natural appearance and prevent sinking skin flap syndrome (or
syndrome of the trephined). Furthermore, restoring patients' functional outcome
and supplementing external defects helps patients improve their self-esteem.
Although early cranioplasty is preferred in recent year, optimal timing for
cranioplasty remains a controversial topic. Autologous bone flaps are the most
ideal substitute for cranioplasty. Complications associated with cranioplasty are
also variable, however, post-surgical infection is most common. Many new
materials and techniques for cranioplasty are introduced. Cost-benefit analysis
of these new materials and techniques can result in different outcomes from
different healthcare systems.
PMID- 28512611
TI - Decompressive Craniectomy in Traumatic Brain Injury: A Review Article.
AB - The importance of treating traumatic brain injury (TBI) is well known worldwide.
Although many studies have been conducted in this topic, there is still much
uncertainty about the effectiveness of surgical treatment in TBI. Recently, good
randomized controlled trial (RCT) papers about the effectiveness of decompressive
craniectomy (DC) in TBI has been published. In this article, we will review the
overall contents of the DC (historical base, surgical technic, rationale,
complications) and the results of the recently published RCT paper.
PMID- 28512613
TI - Comparison of Complications Following Cranioplasty Using a Sterilized Autologous
Bone Flap or Polymethyl Methacrylate.
AB - OBJECTIVE: The aims of current study are to compare complications following
cranioplasty (CP) using either sterilized autologous bone or polymethyl
methacrylate (PMMA), and to identify the risk factors for two of the most common
complications: bone flap resorption (BFR) and surgical site infection (SSI).
METHODS: Between January 2004 and December 2013, 127 patients underwent CP and
were followed at least 12 months. Variables, including sex, age, initial
diagnosis, time interval between decompressive craniectomy (DC) and CP, operation
time, size of bone flap, and presence of ventriculo-peritoneal shunt, were
analyzed to identify the risk factors for BFR and SSI. RESULTS: A total of 97
(76.4%) patients underwent CP using PMMA (Group I) and 30 (23.6%) underwent CP
using autologous bone (Group II). SSI occurred in 8 (8.2%) patients in Group I,
and in 2 (6.7%) in Group II; there was no statistically significant difference
between the groups (p=1.00). No statistically significant risk factors for SSI
were found in either group. In Group I, there was no reported case of BFR. In
Group II patients, BFR developed in 18 (60.0%) patients at the time of CP (Type 1
BFR), and at 12-month follow up (Type 2 BFR) in 4 (13.3%) patients. No
statistically significant risk factors for BFR were found in Group II.
CONCLUSION: CP using sterilized autologous bone result in a significant rate of
BFR. PMMA, however, is a safe alloplastic material for CP, as it has low
complication rate.
PMID- 28512614
TI - Postoperative Contralateral Hematoma in Patient with Acute Traumatic Brain
Injury.
AB - OBJECTIVE: Head injury is a leading cause of death and disability in subjects who
suffer a traumatic accident. Contralateral hematomas after surgery for traumatic
brain injury are rare. However, an unrecognized, these hematomas can cause
devastating results. We presented our experience of these patients and discussed
diagnosis and management. METHODS: This study included 12 traumatic patients with
acute traumatic brain injury who developed delayed contralateral hematoma after
evacuation of an acute hematoma. Clinical and radiographic data was obtained
through review of medical records and radiographs retrospectively. RESULTS: Ten
males and two females were included in the study. Ten (83.3%) patients had severe
head injury (Glasgow Coma Scale [GCS] score <8). Intraoperative brain swelling
during removal of the traumatic subdural hematoma was noted in 10 (83.3%)
patients. A skull fracture on the side contralateral to the acute hematoma was
noted on computed tomography (CT) scans of nine (75%) patients. Three (33.3%)
patients with severe head injury (GCS <8) died. Only (10%) one patient with a
severe head injury had less severe disability. CONCLUSION: A postoperative CT
scan is essential in patients with acute traumatic brain injury and a
contralateral skull fracture or a low GCS score. Our results indicated that it is
very important to evaluate this rare but potentially devastating complication.
PMID- 28512615
TI - Delayed Infarction of Medullar and Cerebellum 3 Months after Vertebral Artery
Injury with C1-2 Fracture: Case Report.
AB - The clinical manifestations of vertebral artery (VA) injury (VAI) after cervical
trauma range from asymptomatic to fatal cerebral infarction. Thrombotic occlusion
and embolization to the distal arteries can cause cerebellar and brain stem
infarction within days after trauma. We report a 64-year-old man who underwent
arthrodesis surgery for C1 and C2 fractures. He had left VAI at the C2 transverse
foramen site but was asymptomatic. The patient experiences brainstem and
cerebellar infarction 3 months after injury to the VA, and we are here to discuss
the treatment of VAI after cervical trauma.
PMID- 28512616
TI - Surgical Management of Syringomyelia Associated with Spinal Adhesive
Arachnoiditis, a Late Complication of Tuberculous Meningitis: A Case Report.
AB - Syringomyelia associated with tuberculous meningitis is an extremely rare
condition. Only a few studies have reported clinical experience with
syringomyelia as a late complication of tuberculous meningitis. Twenty-six years
after a tuberculous meningitis episode, a 44-year-old man presented with
progressively worsening spastic paresis of the lower limbs and impaired urinary
function for 2 years. Radiological examination revealed syringomyelia extending
from the level of C2 to T9 and arachnoiditis with atrophy of the spinal cord
between C2 and T3. We performed laminectomy from C7 to T1, dissected the
arachnoid adhesion and placed a syringo-pleural shunt via keyhole myelotomy. One
year after the operation, his neurological condition improved. The postoperative
control magnetic resonance imaging revealed the correctly located shunt and
significantly diminished syringomyelia cavities. We aim to discuss the mechanism
of syrinx formation following tuberculous meningitis and to share our surgical
therapeutic experience with this rare disease entity.
PMID- 28512617
TI - Vertebral Artery Injury in C2-3 Epidural Schwannoma Resection: A Case Report and
Literature Review.
AB - The incidence of vertebral artery (VA) injury (VAI) in posterior approach tumor
resection surgery is extremely rare, but it can lead to serious complication. In
this case, a 57-year-old man underwent surgery for resection of the tumor
involving left epidural space and neural foramen at C2-3 level. Iatrogenic VAI
occurred suddenly during tumor resection procedure using pituitary forceps.
Immediate local hemostasis and maintaining of perfusion for reducing the risk of
posterior circulation ischemia were performed. Intraoperative angiogram of both
VA and emergent trapping embolization were done as well. It may reduce the risk
of immediate postop complication, and further delayed occurrence. The patient had
no complication after VAI by appropriate intraoperative management. Preoperative
angiographic work up and preparation of endovascular team cooperation are
positively necessary as well as a warning for the VAI during cervical spine
surgery.
PMID- 28512618
TI - Incomplete Isolated C7 Root Injury Caused by Gunshot Wound: A Case Report.
AB - Gunshot wounds to the spine cause severe neurological and/or internal organs
damages. Although most of publications in the literature are realized on military
injuries, increased civilian arming which raises civilian gunshot injuries is a
new social danger causing serious health problems. In gunshot injuries to the
spine; vertebral column, spinal cord and nerve roots are damaged with direct,
indirect and transient cavitation related mechanisms. In this case report, we
present 24 years old male patient who had severe pain and monoparesis in left
upper extremity followed by gunshot injury to the spine with clinical,
radiological and postoperative follow-up findings.
PMID- 28512619
TI - Severe Retrolisthesis at the Adjacent Segment after Lumbar Fusion Combined with
Dynamic Stabilization.
AB - Lumbar fusion using the pedicle screw system is a popular operative procedure,
with favorable clinical results and high fusion rates. However, the risk of
adjacent segment disease after lumbar fusion is problematic. We report a
complicated case of severe retrolisthesis at L3-4 level following dynamic
interspinous process stabilization at L2-3 level and a fusion at L4-5 level. The
radiological and clinical findings of this complication are discussed, and a
review of the literature is presented.
PMID- 28512620
TI - Adjacent Bilateral Stress Pedicle Fractures after Instrumented Lumbar Fusion: A
Case Report.
AB - Bilateral pedicle stress fractures are rare even in the elderly. Bilateral
pedicle fractures are due to post-surgical complications at the level of fusion
or stress related activities in most cases. The authors describe a unique case of
adjacent L4 bilateral pedicle fractures, which developed 4 years after anterior
lumbar interbody fusion with bone cement augmented screw fixation at the L5-S1
level. As far as the authors' knowledge, no similar case has been previously
reported in the literature. The pathophysiological mechanism of this rare entity
is discussed with review of relevant literature.
PMID- 28512621
TI - Spontaneous Acute Subdural Hemorrhage in a Patient with a Tick Borne Bunyavirus
Induced Severe Fever with Thrombocytopenia Syndrome.
AB - We report the first case of severe fever with thrombocytopenia syndrome (SFTS)
and a spontaneous acute subdural hematoma (SDH) in Korea. A 79-year-old male
presented with fever and thrombocytopenia. On the third day of hospitalization,
his mental changed from drowsy to semi-coma. Brain computed tomography indicated
an acute subdural hemorrhage on the right convexity. He was given early
decompressive craniectomy, but did not survive. Real-time reverse transcription
polymerase chain reaction analysis of a blood sample indicated the presence of
SFTS virus (SFTSV). This is the first reported case with intracranial hemorrhage
and SFTS. This case report describes our treatment of a patient with acute SDH
and an infection from a tick-borne species of Bunyaviridae.
PMID- 28512622
TI - Erratum: Risk Factor Analysis for the Recurrence of Chronic Subdural Hematoma: A
Review of 368 Consecutive Surgical Cases.
AB - [This corrects the article on p. 63 in vol. 11, PMID: 27169067.].
PMID- 28512623
TI - Ca2+ Microdomains in T-Lymphocytes.
AB - Early Ca2+ signaling is characterized by occurrence of Ca2+ microdomains formed
by opening of single or clusters of Ca2+ channels, thereby initiating first
signaling and subsequently activating global Ca2+ signaling mechanisms. However,
only few data are available focusing on the first seconds and minutes of Ca2+
microdomain formation and related signaling pathways in activated T-lymphocytes.
In this review, we condense current knowledge on Ca2+ microdomain formation in T
lymphocytes and early Ca2+ signaling, function of Ca2+ microdomains, and
microdomain organization. Interestingly, considering the first seconds of T cell
activation, a triphasic Ca2+ signal is becoming apparent: (i) initial Ca2+
microdomains occurring in the first second of T cell activation, (ii)
amplification of Ca2+ microdomains by recruitment of further channels in the next
5-10 s, and (iii) a transition to global Ca2+ increase. Apparently, the second
messenger nicotinic acid adenine dinucleotide phosphate is the first second
messenger involved in initiation of Ca2+ microdomains. Ryanodine receptors type 1
act as initial Ca2+ release channels in CD4+ T-lymphocytes. Regarding the
temporal correlation of Ca2+ microdomains with other molecular events of T cell
activation, T cell receptor-dependent microdomain organization of signaling
molecules Grb2 and Src homology [SH2] domain-containing leukocyte protein of 65
kDa was observed within the first 20 s. In addition, fast cytoskeletal changes
are initiated. Furthermore, the involvement of additional Ca2+ channels and
organelles, such as the Ca2+ buffering mitochondria, is discussed. Future
research developments will comprise analysis of the causal relation between these
temporally coordinated signaling events. Taken together, high-resolution Ca2+
imaging techniques applied to T cell activation in the past years paved the way
to detailed molecular understanding of initial Ca2+ signaling mechanisms in non
excitable cells.
PMID- 28512624
TI - The Close Interconnection between Mitochondrial Dynamics and Mitophagy in Cancer.
AB - Recent decades have revealed the shape changes of mitochondria and their
regulators to be main players in a plethora of physiological cell processes.
Mitochondria are extremely dynamic organelles whose highly controlled
morphological changes respond to specific and diverse pathophysiological needs.
Thus, their qualitative control is crucial for the determination of cell function
and fate. Moreover, ever-new metabolic changes, mainly attributable to
mitochondrial (dys)functions, are strongly connected to cancer and its
microenvironment. For this reason, the aspects controlling mitochondria activity
and status are in the oncological spotlight. In this review, we elucidate the
most intriguing discoveries related to two apparently independent but strictly
interconnected processes crucial for the organelle functionality and fate,
mitochondrial dynamics, and mitophagy. We will mostly focus on their metabolic
interconnections and regulations that can causally foster a tumoral context.
PMID- 28512625
TI - Using Murine Models to Investigate Tumor-Lymphoid Interactions: Spotlight on
Chronic Lymphocytic Leukemia and Angioimmunoblastic T-Cell Lymphoma.
AB - The role of the tumor microenvironment in leukemias and lymphomas is well
established, yet the intricacies of how the malignant cells regulate and
influence their non-malignant counterparts remain elusive. For example, chronic
lymphocytic leukemia (CLL) is an expansion of malignant CD5+CD19+ B cells, yet
the non-malignant T cells play just as large of a role in disease presentation
and etiology. Herein, we review the dynamic tumor cell to lymphoid repertoire
interactions found in two non-Hodgkin's lymphoma subtypes: CLL and
angioimmunoblastic T-cell lymphoma. We aim to highlight the pivot work done in
the murine models which recapitulate these diseases and explore the insights that
can be gained from studying the immuno-oncological regulation of non-malignant
lymphoid counterparts.
PMID- 28512626
TI - Anti-Restriction Protein, KlcAHS, Promotes Dissemination of Carbapenem
Resistance.
AB - Carbapenemase-producing Klebsiella pneumoniae (KPC) has emerged and spread
throughout the world. A retrospective analysis was performed on carbapenem
resistant K. pneumoniae isolated at our teaching hospital during the period 2009
2010, when the initial outbreak occurred. To determine the mechanism(s) that
underlies the increased infectivity exhibited by KPC, Multilocus Sequence Typing
(MLST) was conducted. A series of plasmids was also extracted, sequenced and
analyzed. Concurrently, the complete sequences of blaKPC-2-harboring plasmids
deposited in GenBank were summarized and aligned. The blaKPC-2 and KlcAHS genes
in the carbapenem-resistant K. pneumoniae isolates were examined. E. coli
strains, carrying different Type I Restriction and Modification (RM) systems,
were selected to study the interaction between RM systems, anti-RM systems and
horizontal gene transfer (HGT). The ST11 clone predominated among 102 carbapenem
resistant K. pneumoniae isolates, all harbored the blaKPC-2 gene; 98% contained
the KlcAHS gene. KlcAHS was one of the core genes in the backbone region of most
blaKPC-2 carrying plasmids. Type I RM systems in the host bacteria reduced the
rate of pHS10842 plasmid transformation by 30- to 40-fold. Presence of the anti
restriction protein, KlcAHS, on the other hand, increased transformation
efficiency by 3- to 6-fold. These results indicate that RM systems can
significantly restrict HGT. In contrast, KlcAHS can disrupt the RM systems and
promote HGT by transformation. These findings suggest that the anti-restriction
protein, KlcAHS, represents a novel mechanism that facilitates the increased
transfer of blaKPC-2 and KlcAHS -carrying plasmids among K. pneumoniae strains.
PMID- 28512627
TI - Laboratory Mice Are Frequently Colonized with Staphylococcus aureus and Mount a
Systemic Immune Response-Note of Caution for In vivo Infection Experiments.
AB - Whether mice are an appropriate model for S. aureus infection and vaccination
studies is a matter of debate, because they are not considered as natural hosts
of S. aureus. We previously identified a mouse-adapted S. aureus strain, which
caused infections in laboratory mice. This raised the question whether laboratory
mice are commonly colonized with S. aureus and whether this might impact on
infection experiments. Publicly available health reports from commercial vendors
revealed that S. aureus colonization is rather frequent, with rates as high as
21% among specific-pathogen-free mice. In animal facilities, S. aureus was
readily transmitted from parents to offspring, which became persistently
colonized. Among 99 murine S. aureus isolates from Charles River Laboratories
half belonged to the lineage CC88 (54.5%), followed by CC15, CC5, CC188, and CC8.
A comparison of human and murine S. aureus isolates revealed features of host
adaptation. In detail, murine strains lacked hlb-converting phages and
superantigen-encoding mobile genetic elements, and were frequently ampicillin
sensitive. Moreover, murine CC88 isolates coagulated mouse plasma faster than
human CC88 isolates. Importantly, S. aureus colonization clearly primed the
murine immune system, inducing a systemic IgG response specific for numerous S.
aureus proteins, including several vaccine candidates. Phospholipase C emerged as
a promising test antigen for monitoring S. aureus colonization in laboratory
mice. In conclusion, laboratory mice are natural hosts of S. aureus and
therefore, could provide better infection models than previously assumed. Pre
exposure to the bacteria is a possible confounder in S. aureus infection and
vaccination studies and should be monitored.
PMID- 28512629
TI - A Modified Behavior Risk Factor Surveillance System to Assess Diabetes Self
management Behaviors and Diabetes Care in Monterrey Mexico: A Cross-sectional
Study.
AB - Type 2 diabetes mellitus (T2DM) is one of the leading causes of death from
worldwide non-communicable diseases. The prevalence of diabetes in the Mexico
(MX)-United States border states exceeds the national rate in both countries. The
economic burden of diabetes, due to decreased productivity, disability, and
medical costs, is staggering and increases significantly when T2DM-related
complications occur. The purpose of this study was to use a modified behavioral
risk factor surveillance system (BRFSS) to describe the T2DM self-management
behaviors, diabetes care, and health perception of a convenience sample of adults
with T2DM in Monterrey, MX. This cross-sectional study design, with convenience
sampling, was conducted with a convenience sample (n = 351) of adults in the
metropolitan area of Monterrey, MX who self-reported a diagnosis of T2DM.
Potential participants were recruited from local supermarkets. Twenty-six
diabetes and health-related items were selected from the BRFSS and administered
in face-to-face interviews by trained data collectors. Data analysis was
conducted using descriptive statistics. The mean age was 47 years, and the mean
length of time with T2DM was 12 years. The majority was taking oral medication
and 34% required insulin. Daily self-monitoring of feet was performed by 56% of
the participants; however, only 8.8% engaged in blood glucose self-monitoring.
The mean number of health-care provider visits was 9.09 per year, and glycated
hemoglobin level (HbA1c) was assessed 2.6 times per year. Finally, only 40.5% of
the participants recalled having a dilated eye exam. We conclude the modified
BRFSS survey administered in a face-to-face interview format is an appropriate
tool for assessing engagement in T2DM self-management behaviors, diabetes care,
and health perception. Extension of the use of this survey in a more rigorous
design with a larger scale survey is encouraged.
PMID- 28512628
TI - Dysplasia of Granulocytes in a Patient with HPV Disease, Recurrent Infections,
and B Lymphopenia: A Novel Variant of WHIM Syndrome?
AB - WHIM syndrome is a condition in which affected persons have chronic peripheral
neutropenia, lymphopenia, abnormal susceptibility to human papilloma virus
infection, and myelokathexis. Myelokathexis refers to the retention of mature
neutrophils in the bone marrow (BM), which accounts for degenerative changes and
hypersegmentation. Most patients present heterozygous autosomal dominant
mutations of the gene encoding CXCR4. Consequently, aberrant CXCL12/CXCR4
signaling impairs the receptor downregulation causing hyperactivation (gain-of
function) that affects BM homing for myelopoiesis and lymphopoiesis and the
release of neutrophils in the bloodstream. We report the case of a 26-year-old
female with severe foot and hand cutaneous warts since childhood, recalcitrant
genital condylomatas, bacterial infections, and intraepithelial cervical
neoplasia. Laboratory tests revealed severe B lymphopenia and HPV high and low
risk types. HIV testing was negative. Not only CXCR4 but also GATA2, NEMO, and
CD40L gene mutations were excluded. BM smears revealed, in the presence of a
normal cellularity, hyperplasia of myeloid cells (MPO positive) and karyorrhexis,
especially in neutrophils and eosinophils. Of note, neutrophils with altered
lobation of nuclei connected by long thin chromatin filaments were observed. Our
patient presented a clinical and histological picture reminiscent of WHIM in the
presence of normal peripheral neutrophil counts and wild-type CXCR4 gene.
Although the BM did not reveal a classical pattern of myelokathexis, the
observation of consistent signs of neutrophil dysplasia has fuelled the
hypothesis of a novel WHIM variant or a novel immunodeficiency. We speculate that
abnormalities that affect CXCR4/CXCL12 pair, including GRK levels or activity,
might be responsible for this WHIM-like disorder.
PMID- 28512630
TI - Hand Grasping Synergies As Biometrics.
AB - Recently, the need for more secure identity verification systems has driven
researchers to explore other sources of biometrics. This includes iris patterns,
palm print, hand geometry, facial recognition, and movement patterns (hand
motion, gait, and eye movements). Identity verification systems may benefit from
the complexity of human movement that integrates multiple levels of control
(neural, muscular, and kinematic). Using principal component analysis, we
extracted spatiotemporal hand synergies (movement synergies) from an object
grasping dataset to explore their use as a potential biometric. These movement
synergies are in the form of joint angular velocity profiles of 10 joints. We
explored the effect of joint type, digit, number of objects, and grasp type. In
its best configuration, movement synergies achieved an equal error rate of 8.19%.
While movement synergies can be integrated into an identity verification system
with motion capture ability, we also explored a camera-ready version of hand
synergies-postural synergies. In this proof of concept system, postural synergies
performed well, but only when specific postures were chosen. Based on these
results, hand synergies show promise as a potential biometric that can be
combined with other hand-based biometrics for improved security.
PMID- 28512633
TI - An Ambulatory Electroencephalography System for Freely Moving Horses: An
Innovating Approach.
AB - Electroencephalography (EEG) that has been extensively studied in humans presents
also a large interest for studies on animal brain processes. However, since the
quality of the recordings is altered by muscular activity, most EEG recordings on
animals are obtained using invasive methods with deeply implanted electrodes.
This requires anesthesia and can thus only be used in laboratory or clinical
settings. As EEG is a very useful tool both for detecting brain alterations due
to diseases or accidents and to evaluate the arousal and attentional state of the
animal, it seemed crucial to develop a tool that would make such recordings
possible in the horse's home environment, with a freely moving horse. Such a tool
should neither be invasive nor cause discomforts to the horse as the usual other
practice which consists, after shaving the zone, in gluing the electrodes to the
skin. To fulfill these requirements, we developed a novel EEG headset adapted to
the horse's head that allows an easy and fast positioning of the electrodes and
that can be used in the home environment on a freely moving horse. In this study,
we show that this EEG headset allows to obtain reliable recordings, and we
propose an original evaluation of an animal's "EEG profile" that allows
comparisons between individuals and situations. This EEG headset opens new
possibilities of investigation on horse cognition, and it can also become a
useful tool for veterinarians to evaluate cerebral disorders or check the
anesthesia level during a surgery.
PMID- 28512631
TI - Genetic Alterations in Gastric Cancer Associated with Helicobacter pylori
Infection.
AB - Gastric cancer is a world health problem and depicts the fourth leading mortality
cause from malignancy in Mexico. Causation of gastric cancer is not only due to
the combined effects of environmental factors and genetic variants. Recent
molecular studies have transgressed a number of genes involved in gastric
carcinogenesis. The aim of this review is to understand the recent basics of gene
expression in the development of the process of gastric carcinogenesis. Genetic
variants, polymorphisms, desoxyribonucleic acid methylation, and genes involved
in mediating inflammation have been associated with the development of gastric
carcinogenesis. Recently, these genes (interleukin 10, Il-17, mucin 1, beta
catenin, CDX1, SMAD4, SERPINE1, hypoxia-inducible factor 1 subunit alpha,
GSK3beta, CDH17, matrix metalloproteinase 7, RUNX3, RASSF1A, TFF1, HAI-2, and COX
2) have been studied in association with oncogenic activation or inactivation of
tumor suppressor genes. All these mechanisms have been investigated to elucidate
the process of gastric carcinogenesis, as well as their potential use as
biomarkers and/or molecular targets to treatment of disease.
PMID- 28512632
TI - Understanding Interleukin 33 and Its Roles in Eosinophil Development.
AB - Over the last decade, significant interest in the contribution of three
"epithelial-derived cytokines," such as thymic stromal lymphopoietin, interleukin
25, and interleukin 33 (IL-33), has developed. These cytokines have been strongly
linked to the early events that occur during allergen exposures and how they
contribute to the subsequent type 2 immune response. Of these three cytokines, IL
33 has proven particularly interesting because of the strong associations found
between both it and its receptor, ST2, in several genome-wide association studies
of allergic diseases. Further work has demonstrated clear mechanisms through
which this cytokine might orchestrate allergic inflammation, including activation
of several key effector cells that possess high ST2 levels, including mast cells,
basophils, innate lymphoid cells, and eosinophils. Despite this, controversies
surrounding IL-33 seem to suggest the biology of this cytokine might not be as
simple as current dogmas suggest including: the relevant cellular sources of IL
33, with significant evidence for inducible expression in some hematopoietic
cells; the mechanistic contributions of nuclear localization vs secretion;
secretion and processing mechanisms; and the biological consequences of IL-33
exposure on different cell types. In this review, we will address the evidence
for IL-33 and ST2 regulation over eosinophils and how this may contribute to
allergic diseases. In particular, we focus on the accumulating evidence for a
role of IL-33 in regulating hematopoiesis and how this relates to eosinophils as
well as how this may provide new concepts for how the progression of allergy is
regulated.
PMID- 28512634
TI - User experience analysis of e-TB Manager, a nationwide electronic tuberculosis
recording and reporting system in Ukraine.
AB - Ukraine has successfully implemented e-TB Manager nationwide as its mandatory
national tuberculosis registry after first introducing it in 2009. Our objective
was to perform an end-of-programme evaluation after formal handover of the
registry administration to Ukraine's Centre for Disease Control in 2015. We
conducted a nationwide, cross-sectional, anonymous, 18-point user experience
survey, and stratified the registry's transaction statistics to demonstrate
usability. Contrary to initial implementation experience, older users (aged >50
years), often with limited or no computer proficiency prior to using the
registry, had significantly better user experience scores for at least six of the
12 measures compared to younger users (aged 18-29 years). Using the registry for
>3 years was associated with significantly higher scores for having capacity,
adequacy of training received and satisfaction with the registry. Of the 5.9
million transactions over a 4-year period, nine out of 24 oblasts (regions) and
Kiev city accounted for 62.5% of all transactions, and corresponded to 59% of
Ukraine's tuberculosis burden. There were 437 unique active users in 486 rayons
(districts) of Ukraine, demonstrating extensive reach. Our key findings
complement the World Health Organization and European Respiratory Society's
agenda for action on digital health to help implement the End TB Strategy.
PMID- 28512635
TI - Drug Susceptibility of 33 Reference Strains of Slowly Growing Mycobacteria to 19
Antimicrobial Agents.
AB - Objectives. Slowly growing mycobacteria (SGM) are prevalent worldwide and cause
an extensive spectrum of diseases. Methods. In this study, the antimicrobial
susceptibility of 33 reference strains of SGM to 19 antimicrobial agents was
tested using a modified microdilution method. Results. Cefmetazole (32/33) and
azithromycin (32/33) exhibited the highest antimicrobial activity, and dapsone
(9/33) exhibited the lowest activity against the tested strains. Cefoxitin
(30/33), cefoperazone (28/33), and cefepime (28/33) were effective against a high
proportion of strains, and macrolides were also highly effective as well as
offering the benefit of convenient oral administration to patients. Linezolid
(27/33), meropenem (26/33), sulfamethoxazole (26/33), and tigecycline (25/33)
showed the highest activity; clofazimine (20/33) and doxycycline (18/33) showed
intermediate activity; and rifapentine (13/33), rifabutin (13/33), and
minocycline (11/33) showed low antimicrobial activity, closely followed by
thioacetazone (10/33) and pasiniazid (10/33), against the tested organisms.
According to their susceptibility profiles, the slowly growing species
Mycobacterium avium and Mycobacterium simiae were the least susceptible to the
tested drugs, whereas Mycobacterium intracellulare, Mycobacterium asiaticum,
Mycobacterium scrofulaceum, Mycobacterium szulgai, Mycobacterium branderi, and
Mycobacterium holsaticum were the most susceptible. Conclusions. In summary,
cephalosporins and macrolides, particularly cefmetazole, azithromycin,
clarithromycin, and roxithromycin, showed good antimicrobial activity against the
reference strains of SGM.
PMID- 28512636
TI - Expression of YAP/TAZ in Keratocystic Odontogenic Tumors and Its Possible
Association with Proliferative Behavior.
AB - The aim of this study is to clarify whether YAP/TAZ is involved in the
pathogenesis and proliferative growth of keratocystic odontogenic tumor (KCOT).
The expression levels of YAP/TAZ and downstream proteins and genes in normal oral
mucosa (OM) and KCOT were determined and compared by immunohistochemistry and
real-time quantitative PCR. The results showed that the expression of YAP/TAZ and
downstream proteins (Cyr61, CTGF) was significantly upregulated in KCOT with
upregulation of Ki-67 compared to OM. Importantly, the mRNA levels of
transcription factors (TEAD1, TEAD4, and RUNX2) and cell cycle related genes
(CDK2, PCNA), which interact with the transcriptional coactivators YAP/TAZ, are
also upregulated in the KCOT. In addition, the results from Spearman rank
correlation test revealed the close relationship between YAP/TAZ and Ki-67, which
was further evidenced by double-labelling immunofluorescence that revealed a
synchronous distribution for YAP/TAZ with Ki-67 in KCOT samples. All the data
suggested YAP/TAZ might be involved in the proliferative behavior of KCOT.
PMID- 28512637
TI - Positive Correlation between IP-10 and IFN-gamma Levels in Rhesus Monkeys (Macaca
mulatta) with Either Naturally Acquired or Experimental Infection of
Mycobacterium tuberculosis.
AB - Numerous studies identify that IP-10 and IFN-gamma are involved in leucocyte
migration and activation and regarded as promising surrogate biomarkers in human
and bovine tuberculosis infection, but there is lack of evidence for IP-10 in
nonhuman primates. In this study, we directly determined IP-10 and IFN-gamma
levels in plasma from 30 healthy monkeys, 30 monkeys with naturally acquired
tuberculosis, 4 monkeys experimentally infected with tuberculosis, and PPD
stimulated whole blood of 14 monkeys with naturally acquired tuberculosis by
ELISA. Higher plasma levels of IP-10 and IFN-gamma were observed in natural
tuberculosis monkeys than in healthy controls. The dynamic changes of plasma IP
10 and IFN-gamma in experimental infections showed consistent representation of a
transient increase during the infection period. After PPD stimulation, release of
IP-10 and IFN-gamma is significantly induced in natural tuberculosis monkeys, but
the stimulation index of IP-10 was significantly lower than IFN-gamma. Further
analysis showed that positive correlation between IP-10 and IFN-gamma existed in
healthy and tuberculosis monkeys. Our findings support plasma IP-10 and IFN-gamma
as biomarkers for monitoring ongoing inflammation of nonhuman primate
tuberculosis, and IFN-gamma is a more valuable diagnostic biomarker.
PMID- 28512638
TI - Seroprevalence and Risk Factors of Bluetongue Virus Infection in Tibetan Sheep
and Yaks in Tibetan Plateau, China.
AB - Bluetongue (BT), caused by bluetongue virus (BTV), is an arthropod-borne viral
disease in ruminants. However, information about BTV infection in yaks in China
is limited. Moreover, no such data concerning BTV in Tibetan sheep is available.
Therefore, 3771 serum samples were collected from 2187 Tibetan sheep and 1584
yaks between April 2013 and March 2014 from Tibetan Plateau, western China, and
tested for BTV antibodies using a commercially available ELISA kit. The overall
seroprevalence of BTV was 17.34% (654/3771), with 20.3% (443/2187) in Tibetan
sheep and 13.3% (211/1584) in yaks. In the Tibetan sheep group, the
seroprevalence of BTV in Luqu, Maqu, Tianzhu, and Nyingchi Prefecture was 20.3%,
20.8%, 20.5%, and 19.1%, respectively. The seroprevalence of BTV in different
season groups varied from 16.5% to 23.4%. In the yak group, BTV seroprevalence
was 12.6%, 15.5%, and 11.0% in Tianzhu, Maqu, and Luqu counties, respectively.
The seroprevalence in different seasons was 12.6%, 15.5%, 15.4%, and 9.0% in
spring, summer, autumn, and winter, respectively. The season was the major risk
factor concerning BTV infection in yaks (P < 0.05). The date of the BTV
seroprevalence in Tibetan sheep and yaks provides baseline information for
controlling BT in ruminants in western China.
PMID- 28512639
TI - Inhibitory Effect of Chemical Constituents Isolated from Artemisia iwayomogi on
Polyol Pathway and Simultaneous Quantification of Major Bioactive Compounds.
AB - Blocking the polyol pathway plays an important role preventing diabetic
complications. Therefore, aldose reductase (AR) and advanced glycation
endproducts (AGEs) formation has significant effect on diabetic complications.
Artemisia iwayomogi has long been used as treatment of various diseases in Korea.
However, no literatures have reported on AR and AGEs formation inhibitory
activities of A. iwayomogi. For these reasons, we aimed to assess that A.
iwayomogi had potential as anti-diabetic complications agents. We led to
isolation of two coumarins (1 and 2), nine flavonoids (3-11), five caffeoylquinic
acids (12-16), three diterpene glycosides (17-19), and one phenolic compound (20)
from A. iwayomogi. Among them, hispidulin (4), 6-methoxytricin (6),
arteanoflavone (7), quercetin-3-gentiobioside (10), 1,3-di-O-caffeoylquinic acid
(13), and suavioside A (18) were first reported on the isolation from A.
iwayomogi. Not only two coumarins (1 and 2), nine flavonoids (3-11), and five
caffeoylquinic acids (12-16) but also extracts showed significant inhibitor on AR
and AGEs formation activities. We analyzed contents of major bioactive compounds
in Korea's various regions of A. iwayomogi. Overall, we selected Yangyang,
Gangwon-do, from June, which contained the highest amounts of bioactive
compounds, as suitable areas for cultivating A. iwayomogi as preventive or
therapeutic agent in the treatment of diabetic complications.
PMID- 28512640
TI - Relationship between HLA-DQ Gene Polymorphism and Hepatitis B Virus Infection.
AB - Hepatitis B virus (HBV) infection is the predominant risk factor for chronic
hepatitis B (CHB). The association between HBV infection and human leukocyte
antigen- (HLA-) DQ polymorphism (rs2856718 and rs7453920) has been demonstrated
in other studies; however, the results were controversial or inconclusive.
Therefore, to derive a more precise estimation of the association, a meta
analysis was performed. Crude odds ratios (ORs) and their 95% confidence
intervals (CIs) were used to assess the strength of association between HLA-DQ
polymorphism (rs2856718 and rs7453920) and HBV infection risk. A total of 11
articles were used to evaluate the effect of the two polymorphisms on risk of HBV
infection. The pooled data showed that HLA-DQ rs2856718-G polymorphism showed
protection against HBV infection, and rs2856718-A was a risk factor for chronic
HBV infection. The pooled risk estimates indicated that HLA-DQ rs7453920-A
polymorphism was associated with decreased risk of HBV infection, and rs7453920-G
serves as a risk factor in HBV infection. However, these stratified analyses were
lacking credibility due to the limitation of correlational study numbers; further
investigation on a large population and different ethnicities is warranted.
PMID- 28512641
TI - Podocyte Autophagy: A Potential Therapeutic Target to Prevent the Progression of
Diabetic Nephropathy.
AB - Diabetic nephropathy (DN), a leading cause of end-stage renal disease (ESRD),
becomes a worldwide problem. Ultrastructural changes of the glomerular filtration
barrier, especially the pathological changes of podocytes, lead to proteinuria in
patients with diabetes. Podocytes are major components of glomerular filtration
barrier, lining outside of the glomerular basement membrane (GBM) to maintain the
permeability of the GBM. Autophagy is a high conserved cellular process in
lysosomes including impaired protein, cell organelles, and other contents in the
cytoplasm. Recent studies suggest that activation of autophagy in podocytes may
be a potential therapy to prevent the progression of DN. Here, we review the
mechanisms of autophagy in podocytes and discuss the current studies about
alleviating proteinuria via activating podocyte autophagy.
PMID- 28512643
TI - Diagnostic and Research Aspects of Small Intestinal Disaccharidases in Coeliac
Disease.
AB - Disaccharidases (DS) are brush border enzymes embedded in the microvillous
membrane of small intestinal enterocytes. In untreated coeliac disease (CD), a
general decrease of DS activities is seen. This manuscript reviews different
aspects of DS activities in CD: their utility in the diagnosis and their
application to in vitro toxicity testing. The latter has never been established
in CD research. However, with the recent advances in small intestinal organoid
techniques, DS might be employed as a biomarker for in vitro studies. This
includes establishment of self-renewing epithelial cells raised from tissue,
which express differentiation markers, including the brush border enzymes.
Determining duodenal DS activities may provide additional information during the
diagnostic workup of CD: (i) quantify the severity of the observed histological
lesions, (ii) provide predictive values for the grade of mucosal villous atrophy,
and (iii) aid diagnosing CD where minor histological changes are seen. DS can
also provide additional information to assess the response to a gluten-free diet
as marked increase of their activities occurs four weeks after commencing it.
Various endogenous and exogenous factors affecting DS might also be relevant when
considering investigating the role of DS in other conditions including noncoeliac
gluten sensitivity and DS deficiencies.
PMID- 28512645
TI - Regulation of Discrete Functional Responses by Syk and Src Family Tyrosine
Kinases in Human Neutrophils.
AB - Neutrophils play a critical role in innate immunity and also influence adaptive
immune responses. This occurs in good part through their production of
inflammatory and immunomodulatory cytokines, in conjunction with their prolonged
survival at inflamed foci. While a picture of the signaling machinery underlying
these neutrophil responses is now emerging, much remains to be uncovered. In this
study, we report that neutrophils constitutively express various Src family
isoforms (STKs), as well as Syk, and that inhibition of these protein tyrosine
kinases selectively hinders inflammatory cytokine generation by acting
posttranscriptionally. Accordingly, STK or Syk inhibition decreases the
phosphorylation of signaling intermediates (e.g., eIF-4E, S6K, and MNK1) involved
in translational control. By contrast, delayed apoptosis appears to be
independent of either STKs or Syk. Our data therefore significantly extend our
understanding of which neutrophil responses are governed by STKs and Syk and
pinpoint some signaling intermediates that are likely involved. In view of the
foremost role of neutrophils in several chronic inflammatory conditions, our
findings identify potential molecular targets that could be exploited for future
therapeutic intervention.
PMID- 28512642
TI - Role of Nuclear Factor Erythroid 2-Related Factor 2 in Diabetic Nephropathy.
AB - Diabetic nephropathy (DN) is manifested as increased urinary protein level,
decreased glomerular filtration rate, and final renal dysfunction. DN is the
leading cause of end-stage renal disease worldwide and causes a huge societal
healthcare burden. Since satisfied treatments are still limited, exploring new
strategies for the treatment of this disease is urgently needed. Oxidative stress
takes part in the initiation and development of DN. In addition, nuclear factor
erythroid 2-related factor 2 (Nrf2) plays a key role in the cellular response to
oxidative stress. Thus, activation of Nrf2 seems to be a new choice for the
treatment of DN. In current review, we discussed and summarized the therapeutic
effects of Nrf2 activation on DN from both basic and clinical studies.
PMID- 28512644
TI - Analysis of Serum Cytokines and Single-Nucleotide Polymorphisms of SOD1, SOD2,
and CAT in Erysipelas Patients.
AB - Increased free radical production had been documented in group A (beta-hemolytic)
streptococcus infection cases. Comparing 71 erysipelas patients to 55 age-matched
healthy individuals, we sought for CAT, SOD1, and SOD2 single polymorphism
mutation (SNPs) interactions with erysipelas' predisposition and serum cytokine
levels in the acute and recovery phases of erysipelas infection. Whereas female
patients had a higher predisposition to erysipelas, male patients were prone to
having a facial localization of the infection. The presence of SOD1 G7958, SOD2
T2734, and CAT C262 alleles was linked to erysipelas' predisposition. T and C
alleles of SOD2 T2734C individually were linked to patients with bullous and
erythematous erysipelas, respectively. G and A alleles of SOD1 G7958A
individually were associated with lower limbs and higher body part localizations
of the infection, respectively. Serum levels of IL-1beta, CCL11, IL-2Ralpha,
CXCL9, TRAIL, PDGF-BB, and CCL4 were associated with symptoms accompanying the
infection, while IL-6, IL-9, IL-10, IL-13, IL-15, IL-17, G-CSF, and VEGF were
associated with predisposition and recurrence of erysipelas. While variations of
IL-1beta, IL-7, IL-8, IL-17, CCL5, and HGF were associated with the SOD2 T2734C
SNP, variations of PDFG-BB and CCL2 were associated with the CAT C262T SNP.
PMID- 28512648
TI - Revision of biliary sphincterotomy by re-cut, balloon dilation or temporary
stenting: comparison of clinical outcome and complication rate (with video).
AB - Background and study aims Revision of endoscopic retrograde
cholangiopancreatography (ERCP) may be necessary following previous biliary
endoscopic sphincterotomy for recurrent biliary symptoms related to biliary stone
recurrence, cholangitis or post-biliary endoscopic sphincterotomy (bEST)
papillary stenosis and cholestasis. The aim of this retrospective study was to
evaluate the clinical outcome and complication rate associated with re-cut,
balloon dilation and biliary metal stenting in revision ERCP. Patients and
methods From January 2010 to January 2015, 139 subjects with stigma of a previous
sphincterotomy required a revision ERCP (64 Men/75 Women; mean age 71 years;
range 32 - 101 years). The most appropriate technique (re-cut, balloon dilation
or fully covered self-expandable metal stent [FCSEMS] placement) was tailored
according to underlying pathologies and anatomical features. Results Technical
success was achieved in all cases (100 %). Clinical success (definitive clearance
of common bile duct stones and liver test normalization) was achieved in 127 out
of 139 patients (91.4 %) with a mean follow up of 12 months. 12 clinical failures
occurred: 11 patients required a new ERCP after an average of 9 months meanwhile
1 patient required surgery for definite treatment. The overall complication rate
was 9 % (13 /139) with 5 acute complications (intra-procedural) and 8 short-term
complications (before 1 month). Group specific overall complication rates were as
follow: re-cut 11.5 % (8 bleeds and 3 perforations), balloon dilation 25 % (4
mild PEP [post-ERCP pancreatitis]), FCSEMS 14.3 % (1 moderate PEP), re-cut +
balloon dilation and re-cut + FCSEMS 0 %. A statistically significant higher risk
of post-ERCP pancreatitis was highlighted in the balloon dilation group meanwhile
re-cut was burdened by a higher risk of bleeding and perforation. Conclusions
Revision ERCP following previous bEST is a feasible procedure enabling clinical
success in most cases. Different approaches are available and must be considered
according to underlying pathologies. Re-cut is burdened by a higher risk of
perforation and bleeding compared to balloon dilation and SEMS meanwhile balloon
dilation is associated to increased risk of PEP.
PMID- 28512647
TI - Early esophagogastroduodenoscopy is associated with better Outcomes in upper
gastrointestinal bleeding: a nationwide study.
AB - Background and study aims We analyzed NIS (National Inpatient Sample) database
from 2007 - 2013 to determine if early esophagogastroduodenoscopy (EGD) (24
hours) for upper gastrointestinal bleeding improved the outcomes in terms of
mortality, length of stay and costs. Patients and methods Patients were
classified as having upper gastrointestinal hemorrhage by querying all diagnostic
codes for the ICD-9-CM codes corresponding to upper gastrointestinal bleeding.
For these patients, performance of EGD during admission was determined by
querying all procedural codes for the ICD-9-CM codes corresponding to EGD; early
EGD was defined as having EGD performed within 24 hours of admission and late EGD
was defined as having EGD performed after 24 hours of admission. Results A total
of 1,789,532 subjects with UGIH were identified. Subjects who had an early EGD
were less likely to have hypovolemia, acute renal failure and acute respiratory
failure. On multivariable analysis, we found that subjects without EGD were 3
times more likely to die during the admission than those with early EGD. In
addition, those with late EGD had 50 % higher odds of dying than those with an
early EGD. Also, after adjusting for all factors in the model, hospital stay was
on average 3 and 3.7 days longer for subjects with no or late EGD, respectively,
then for subjects with early EGD. Conclusion Early EGD (within 24 hours) is
associated with lower in-hospital mortality, morbidity, shorter length of stay
and lower total hospital costs.
PMID- 28512646
TI - MRI in Glioma Immunotherapy: Evidence, Pitfalls, and Perspectives.
AB - Pseudophenomena, that is, imaging alterations due to therapy rather than tumor
evolution, have an important impact on the management of glioma patients and the
results of clinical trials. RANO (response assessment in neurooncology) criteria,
including conventional MRI (cMRI), addressed the issues of pseudoprogression
after radiotherapy and concomitant chemotherapy and pseudoresponse during
antiangiogenic therapy of glioblastomas (GBM) and other gliomas. The development
of cancer immunotherapy forced the identification of further relevant response
criteria, summarized by the iRANO working group in 2015. In spite of this, the
unequivocal definition of glioma progression by cMRI remains difficult
particularly in the setting of immunotherapy approaches provided by checkpoint
inhibitors and dendritic cells. Advanced MRI (aMRI) may in principle address this
unmet clinical need. Here, we discuss the potential contribution of different
aMRI techniques and their indications and pitfalls in relation to biological and
imaging features of glioma and immune system interactions.
PMID- 28512650
TI - Effect of antimicrobial photodynamic therapy ?and laser alone as adjunct to
mechanical debridement in the management of halitosis: A systematic review.
AB - OBJECTIVE: The aim of the present study was to assess the efficacy of laser
therapy (LT) and antimicrobial photodynamic therapy (aPDT) as adjunct to
mechanical debridement (MD) on the management of halitosis. DATA SOURCES: In
order to address the focused question "Is MD with adjunct LT and/or aPDT more
effective in the management of halitosis compared with MD alone?" an electronic
search without time or language restrictions was conducted up to January 2017 in
indexed databases using the combination of different key words including
photochemotherapy, lasers, light, photodynamic therapy, halitosis, and bad
breath. The exclusion criteria included qualitative and/or quantitative reviews,
case reports, case series, commentaries, letters to the editor, interviews, and
updates. RESULTS: Six randomized control trials were included and processed for
data extraction. Results from all studies reported that MD with adjunct LT or
aPDT is more effective in reducing halitosis and/or volatile sulfur compounds
concentration associated with oral conditions compared with MD alone. One study
reported a significant reduction in bacterial colony forming units on the dorsum
of the tongue among patients with coated tongue receiving MD with aPDT compared
with MD alone. CONCLUSION: The efficacy of aPDT and/or LT on halitosis management
remains unclear. Further well-designed randomized clinical trials assessing the
efficacy of mechanical debridement with LT or aPDT on the halitosis treatment are
needed.
PMID- 28512651
TI - Premium protocol for planning a periodontal-restorative approach: Conservative,
predictable, ?and reproducible.
AB - Planning oral rehabilitation that involves an interdisciplinary approach is
challenging, especially when it includes changes in the morphologic aspects of
teeth and the architecture of gingival tissues. Patients commonly complain about
the esthetics of maxillary anterior teeth, especially when diastemata are
present. A guideline known as the golden proportion can be used to establish
adequate width distribution of anterior teeth. Tooth proportion is also affected
by incisogingival tooth length, hence gingival contouring should be evaluated as
well. In these situations, the width-to-height ratio of 0.75:0.78 in the
maxillary anterior teeth could be used to obtain wax-ups and a surgical guide,
resulting in a more predictable esthetic outcome. Therefore, this clinical report
describes a protocol for the planning of a periodontal-restorative approach with
two wax-ups and a surgical guide using the golden proportion width-to-height
ratio of 0.75:0.78 for the treatment of maxillary anterior teeth with diastemata
using minimum thickness lithium disilicate veneers.
PMID- 28512649
TI - Purification and Characterization of Schwann Cells from Adult Human Skin and
Nerve.
AB - Despite its modest capacity for regeneration, peripheral nervous system injury
often results in significant long-term disability. Supplementing peripheral
nervous system injury with autologous Schwann cells (SCs) may serve to rejuvenate
the postinjury environment to enhance regeneration and ultimately improve
functional outcomes. However, human nerve-derived SC (hN-SC) collection
procedures require invasive surgical resection. Here, we describe the
characterization of SCs from adult human skin (hSk-SCs) of four male donors
ranging between 27 and 46 years old. Within five weeks of isolating and culturing
adherent mixed skin cells, we were able to obtain 3-5 million purified SCs. We
found that hSk-SCs appeared transcriptionally indistinguishable from hN-SCs with
both populations exhibiting expression of SC genes including: SOX10, SOX9, AP2A1,
CDH19, EGR1, ETV5, PAX3, SOX2, CX32, DHH, NECL4, NFATC4, POU3F1, S100B, and YY1.
Phenotypic analysis of hSk-SCs and hN-SCs cultures revealed highly enriched
populations of SCs indicated by the high percentage of NES+ve, SOX10+ve, s100+ve
and p75+ve cells, as well as the expression of a battery of other SC-associated
proteins (PAX3, CDH19, ETV5, SOX2, POU3F1, S100B, EGR2, and YY1). We further show
that both hSk-SCs and hN-SCs are capable of promoting axonal growth to similar
degrees and that a subset of both associate with regenerating axons and form
myelin following transplantation into the injured mouse sciatic nerve.
Interestingly, although the majority of both hSk-SCs and hN-SCs maintained SOX10
immunoreactivity following transplant, only a subset of each activated the
promyelinating factor, POU3F1, and were able to myelinate. Taken together, we
demonstrate that adult hSk-SCs are genetically and phenotypically
indistinguishable to hN-SCs.
PMID- 28512652
TI - Comparison of simplistic biofilm models for ?evaluating irrigating solutions.
AB - OBJECTIVE: Many innovations have recently been implemented in the field of
endodontics, often based on a variety of in-vitro/ex-vivo test setups. It was the
goal of this research to compare different biofilm models for evaluating the
effectiveness of rinsing solutions. METHOD AND MATERIALS: Three different models
have been applied in this study, including petri dishes with nutrient medium,
arrays of human dentin disks, and split bovine root segments. The susceptibility
of biofilms formed by Enterococcus faecalis to commonly used endodontic irrigants
was tested. RESULTS: While citric acid 3% did not show an inhibitory effect on
solid medium, mean maximum inhibition areolae of 9.8 +/- 1.6 mm were found for
sodium hypochlorite 3%. Fluorescein solution was shown to penetrate dentin
tubules to a depth of 0.5 to 1 mm, indicating that the dentin tubules are not
freely accessible, but clotted by E faecalis biofilms. Rinsing root canals with a
combination of citric acid, hydrogen peroxide, chlorhexidine, and sodium
hypochlorite removed bacterial biofilms from the dentin tubules only to a depth
of 0.5 mm, while bacteria in deeper regions were not affected. CONCLUSION:
Standard irrigating solutions inhibit bacterial growth; however, due to the
morphology of the tooth, the effect of irrigating media is restricted to the root
canal and the adjacent volume of dentin tubules. Results from standardizable
diffusion tests seem not to be predictive for clinical performance of irrigating
solutions.
PMID- 28512658
TI - Effect of the material properties on the crumpling of a thin sheet.
AB - While simple at first glance, the dense packing of sheets is a complex phenomenon
that depends on material parameters and the packing protocol. We study the effect
of plasticity on the crumpling of sheets of different materials by performing
isotropic compaction experiments on sheets of different sizes and elasto-plastic
properties. First, we quantify the material properties using a dimensionless
foldability index. Then, the compaction force required to crumple a sheet into a
ball as well as the average number of layers inside the ball are measured. For
each material, both quantities exhibit a power-law dependence on the diameter of
the crumpled ball. We experimentally establish the power-law exponents and find
that both depend nonlinearly on the foldability index. However the exponents that
characterize the mechanical response and morphology of the crumpled materials are
related linearly. A simple scaling argument explains this in terms of the
buckling of the sheets, and recovers the relation between the crumpling force and
the morphology of the crumpled structure. Our results suggest a new approach to
tailor the mechanical response of the crumpled objects by carefully selecting
their material properties.
PMID- 28512653
TI - Simplified technique for easy extraction of impacted supernumerary teeth using
guided surgery.
AB - Most mesiodens remain impacted and can affect the growth and development of
adjacent permanent teeth. Impacted mesiodens are usually located in an
intraosseous position associated with complicated anatomical structures,
necessitating minimally invasive surgical approaches. This article demonstrates a
simple customized surgical stent for extraction of impacted mesiodens. Its use
and advantages are described.
PMID- 28512659
TI - Extensive characterization of magnetic microrods observed using optical
microscopy.
AB - The usage of micro or nanorods is steadily increasing in various applications
from fundamental research to industry. Therefore their geometrical, mechanical
and eventually magnetic properties need to be well determined. Here, using an
optical microscope equipped with magnetic tweezers, we report an experimental
procedure to obtain all those information on a single magnetic rod. In
particular, we measure magnetic susceptibility chi by analyzing the deformation
of a rod subjected to a uniform magnetic field. To do so, we refine a theoretical
model which takes into account the variation of chi with the internal field. We
prove experimentally that this model yields consistent measurements, at any value
of the field strength and the incidence angle. From the combination of the
different measurements, we also deduce the number of iron oxide nanoparticles
which are embedded within the polymer matrix of the superparamagnetic rods under
study.
PMID- 28512660
TI - Selective protein recognition in supported lipid bilayer arrays by tailored, dual
mode deep cavitand hosts.
AB - Self-folding deep cavitands with variably functionalized upper rims are able to
selectively immobilize proteins at a biomimetic supported lipid bilayer surface.
The immobilization process takes advantage of the dual-mode binding capabilities
of the hosts, combining a defined binding pocket with upper rim charged/H-bonding
groups. A variety of proteins can be selectively immobilized at the bilayer
interface, either via complementary charge/H-bonding interactions, cavity-based
molecular recognition, or a combination of both. The immobilization process can
be used to bind unmodified native proteins, epitopes for bioadhesion, or proteins
covalently modified with suitable RNMe3+ binding "handles" and charged groups
that can either match or mismatch with the cavitand rim. The immobilization
process can be monitored in real time using surface plasmon resonance (SPR)
spectroscopy, and applied to the construction of cavitand:lipid arrays using the
hosts and trehalose vitrified phospholipid vesicles. The selective, dual-mode
protein recognition is maintained in the arrays, and can be visualized using SPR
imaging.
PMID- 28512662
TI - A hospital-wide transition from paper to digital problem-oriented clinical notes.
A descriptive history and cross-sectional survey of use, usability, and
satisfaction.
AB - OBJECTIVES: To evaluate the use, usability, and physician satisfaction of a
locally developed problem-oriented clinical notes application that replaced paper
based records in a large Dutch university medical center. METHODS: Using a
clinical notes database and an application event log file and a cross-sectional
survey of usability, authors retrospectively analyzed system usage for medical
specialties, users, and patients over 4 years. A standardized questionnaire
measured usability. Authors analyzed the effects of sex, age, professional
experience, training hours, and medical specialty on user satisfaction via
univariate analysis of variance. Authors also examined the correlation between
user satisfaction in relation to users' intensity of use of the application.
RESULTS: In total 1,793 physicians used the application to record progress notes
for 219,755 patients. The overall satisfaction score was 3.2 on a scale from 1
(highly dissatisfied) to 5 (highly satisfied). A statistically significant
difference occurred in satisfaction by medical specialty, but no statistically
significant differences in satisfaction took place by sex, age, professional
experience, or training hours. Intensity of system use did not correlate with
physician satisfaction. CONCLUSIONS: By two years after the start of the
implementation, all medical specialties utilized the clinical notes application.
User satisfaction was neutral (3.2 on a 1-5 scale). Authors believe that the
significant factors facilitating this transition mirrored success factors
reported by other groups: a generic, consistent, and transparent design of the
application; intensive collaboration; continuous monitoring; and an incremental
rollout.
PMID- 28512663
TI - Advancing the integration of hospital IT. Pitfalls and perspectives when
replacing specialized software for high-risk environments with enterprise system
extensions.
AB - BACKGROUND: Planning and controlling surgical operations hugely impacts upon
productivity, patient safety, and surgeons' careers. Established, specialized
software for this task is being increasingly replaced by "Operating Room (OR)
modules" appended to enterprise-wide resource planning (ERP) systems. As a
result, usability problems are re-emerging and require developers' attention.
OBJECTIVE: Systematic evaluation of the functionality and social repercussions of
a global, market-leading IT business control system (SAP R3, Germany), adapted
for real-time OR process steering. METHODS: Field study involving document
analyses, interviews, and a 73-item survey addressed to 77 qualified (> 1-year
system experience) senior planning executives (end users; "planners") working in
surgical departments of university hospitals. RESULTS: Planners reported that 57%
of electronic operation requests contained contradictory information. Key screens
contained clinically irrelevant areas (36 +/- 29%). Compared to the legacy
system, users reported either no improvements or worse performance, in regard to
co-ordination of OR stakeholders, intra-day program changes, and safety. Planners
concluded that the ERP-planning module was "non-intuitive" (66%), increased
planning work (56%, p=0.002), and did not impact upon either organizational
mishap spectrum or frequency. Interviews evidenced intra-institutional power
shifts due to increased system complexity. Planners resented e.g. a trend towards
increased personal culpability for mishap. CONCLUSIONS: Highly complex enterprise
system extensions may not be directly suited to specific process steering tasks
in a high risk/low error-environment like the OR. In view of surgeons' high
primary task load, the repeated call for simpler IT is an imperative for ERP
extensions. System design should consider a) that current OR IT suffers from an
input limitation regarding planning-relevant real-time data, and b) that there
are social processes that strongly affect planning and particularly ERP use
beyond algorithms. Real improvement of clinical IT tools requires their
independent evaluation according to standards developed for pharmaceutical
subjects.
PMID- 28512664
TI - Antidepressants have Anti-inflammatory Effects that may be Relevant to
Dermatology: A Systematic Review.
AB - There is increasing evidence of clinically relevant anti-inflammatory effects of
monoaminergic antidepressants. PubMed and Ovid databases were searched
systematically for the use and efficacy of antidepressants in association with 5
common inflammatory skin disorders: chronic urticaria, psoriasis, atopic
dermatitis, other eczema, and alopecia areata. From January 1984 to June 2016,
publications included a total of 1,252 dermatological patients in 28 trials or
case reports. These unambiguously reported a reduced burden of dermatological
symptoms in relation to treatment with antidepressants. Several randomized
controlled trials of first-generation antidepressants have been published, while
studies of modern antidepressants are usually open-label, yet more informative,
regarding patients' characteristics and study procedures. These overall positive
findings may indicate a rationale, beyond treating comorbid psychiatric
disorders, for the use of antidepressants in dermatology. Further research into
modern tolerable antidepressants, including selective serotonin re-uptake
inhibitors, mirtazapine and bupropion, is required.
PMID- 28512665
TI - Involvement of u-opioid Receptors and kappa-opioid Receptors in Itch-related
Scratching Behaviour of Imiquimod-induced Psoriasis-like Dermatitis in Mice.
AB - The pathogenesis of psoriatic itch is poorly understood. The aim of this study
was to investigate the involvement of opioid receptors in scratching behaviour of
imiquimod-induced psoriasis-like dermatitis model mice. Topical application of 5%
imiquimod cream to the rostral back skin of mice induced antihistamine-resistant
scratching behaviour. The expression of u-opioid receptor (MOR) protein increased
in the epidermis, dorsal root ganglia (DRG) and spinal cord of imiquimod-treated
mice. In contrast, the expression of kappa-opioid receptor (KOR) protein
decreased in the DRG and spinal cord of imiquimod-treated mice, and was
undetectable in the epidermis of both groups. Topical or intraperitoneal
administration of the MOR antagonist naloxone and oral administration of the
centrally acting KOR agonist ICI-199,441 inhibited scratching behaviour, whereas
oral administration of the peri-pherally-selective KOR agonist asimadoline did
not. These results suggest that peripheral and central MOR and central KOR may be
involved in the modulation of scratching behaviour in imiquimod-treated mice.
PMID- 28512666
TI - Diagnostic Efficacy of Digital Dermoscopy and Clinical Findings in Thin Melanoma
of the Lower Limbs.
AB - The introduction of dermoscopy has improved the accuracy of diagnosis of
melanoma. However, early stage melanoma can be difficult to diagnose. Eighty-nine
cases of thin melanoma with a Breslow thickness <=1 mm located on the lower limb
and diagnosed between 2008 and 2016 were assessed using 4 dermoscopic algorithms:
(i) modified pattern analysis; (ii) ABCD rule of dermoscopy; (iii) 7-point
checklist; and (iv) Menzies' method. Two groups of early stage melanomas of the
legs were identified: "difficult to diagnose melanomas" (DDM) and "non-difficult
to diagnose melanomas" (NDDM). In our series the dermoscopic features of DDM were
difficult to differentiate from melanocytic naevi, and the reticular pattern was
the most frequently observed. "Depigmentation" was the only specific criterion
associated with DDM. The sensitivity of diagnostic systems for thin melanomas of
the lower limbs was lower than in previous studies. This result could be related
to the lower mean Breslow thickness of the invasive melanomas in our sample and
the high number of melanomas in situ. In conclusion, early stage melanoma of the
legs may be difficult to detect at clinical examination or with dermoscopic
examination alone. Focusing on depigmentation in dermoscopy associated with
anamnestic features could be a useful tool to detect difficult thin melanomas. In
addition, sequential dermoscopy is recommended for high-risk patients with
previous melanomas or atypical mole syndrome.
PMID- 28512667
TI - Involvement of Leukotriene B4 Released from Keratinocytes in Itch-associated
Response to Intradermal Interleukin-31 in Mice.
AB - A recent study suggests that interleukin-31 (IL-31) exerts its effect via
indirect mechanisms rather than through direct stimulation of cutaneous nerves.
However, the underlying peripheral mechanisms of IL-31-induced itch in the skin
remain unclear. Therefore, the present study investigated the peripheral
mechanisms underlying IL-31-induced itch in mice. IL-31-induced itch-related
response was inhibited by anti-allergic drugs (tranilast and azelastine), but not
by an H1 histamine receptor antagonist (terfenadine). Furthermore, a 5
lipoxygenase inhibitor (zileuton), but not a cyclooxygenase inhibitor
(indomethacin), and a leuko-triene B4 (LTB4) receptor antagonist (CMHVA)
attenuated the action of IL-31. IL-31 receptor-immunoreactivity was observed in
the epidermis and primary sensory neurones. IL-31 receptor mRNA was expressed in
mouse keratinocytes and dorsal root ganglia neurones. IL-31 increased the
production of LTB4 in mouse keratinocytes. These results suggest that IL-31
elicits itch not only through direct action on primary sensory neurones, but also
by inducing LTB4 production in keratinocytes.
PMID- 28512668
TI - Prevalence of Cancer in Adult Patients with Atopic Dermatitis: A Nationwide
Study.
AB - is missing (Short communication).
PMID- 28512669
TI - Combined Fractional Treatment of Acne Scars Involving Non-ablative 1,550-nm
Erbium-glass Laser and Micro-needling Radiofrequency: A 16-week Prospective,
Randomized Split-face Study.
AB - An optimized therapeutic regimen involving a non-ablative fractionated laser or
radiofrequency therapy for acne scars has not yet been established. To evaluate
whether the combination of a non-ablative fractional laser (NAF) and fractional
micro-needling radiofrequency (FMR) has clinical advantages for the treatment of
atrophic acne scars compared with NAF alone, a 16-week prospective, randomized
split-face study was performed. Each facial side of a patient was treated with 3
sessions of either NAF with FMR or NAF alone, with a 4-week interval between each
session. Although both sides demonstrated significant decreases in the echelle
d'evaluation clinique des cicatrices d'acne (ECCA) score, the facial side treated
using the combination regimen demonstrated greater improvement in ECCA score
regarding degree and onset time than the NAF-treated side. Histopathological and
immunohistochemical results confirmed the clinical findings. This study
demonstrated that a combination regimen involving NAF and FMR could be a viable
option with satisfactory efficacy.
PMID- 28512670
TI - Disrupted Skin Barrier is Associated with Burning Sensation after Topical
Tacrolimus Application in Atopic Dermatitis.
PMID- 28512671
TI - Biologic Therapies in HIV-infected Patients with Psoriasis: An Italian
Experience.
PMID- 28512672
TI - Sezary Syndrome with Nodal CD30-positive Manifestation Treated with Brentuximab
Vedotin and Extracorporeal Photopheresis.
PMID- 28512674
TI - Preparing pathology for precision medicine: challenges and opportunities.
PMID- 28512673
TI - Hepatozoon caimani Carini, 1909 (Adeleina: Hepatozoidae) in wild population of
Caiman yacare Daudin, 1801 (Crocodylia: Alligatoridae), Pantanal, Brazil.
AB - Previous studies showed infections of Hepatozoon caimani in wild populations of
caimans in wide regions from Brazil; some of those demonstrated that trophic
chain are linked to natural infections through paratenic hosts or by the direct
ingestion of vectors. These studies life cycle of H. caimani contributed
inestimably to the knowledge of transmission routes, yet but lack enhancement
tools for better detail of parasite. This study reports the forms in the blood
and tissues, and also partial molecular characterization of the H. caimani
following part of the 18S rRNA region. In the southern Pantanal, there were
sampling 39 adult caimans (Caiman yacare), where 31 (79.5%) were parasitized by
H. caimani. Free gametocytes had an average intensity of 19.6% and
intraerythrocytic forms 7.42%, in the blood smears. In stained smears of the
liver and lungs of naturally infected caimans which were examined, monozoic and
dizoic cysts were found in these tissues, generally next to the vessels. In the
histopathology, meronts were observed in the wall of vessels from liver and
kidney ducts. Blood samples were forwarded to PCR process and produced amplicons
with about 600 and 900 bp, respectively, for the primers HEPF300/HEP900 and
HEMO1/HEMO2. This was the first report of molecular confirmation of Hepatozoon in
populations of naturally infected caimans of morphological detail of the
gametocytes in scanning electron microscopy and histology of merogony in livers
and kidneys of C. yacare.
PMID- 28512675
TI - Selection and characterization of an anaerobic microbial consortium with high
adaptation to crude glycerol for 1,3-propanediol production.
AB - Crude glycerol is an ideal feedstock for bioproduction of 1,3-propanediol (1,3
PDO) while pure culture always shows low substrate tolerance and limited
productivity. In this study, an anaerobic microbial consortium for conversion of
crude glycerol was selected and its 1,3-PDO production capacity was evaluated.
The consortium was obtained from anaerobic activated sludge by 19 serial
transfers and mainly consisted of 94.64% Clostridiaceae and 4.47%
Peptostreptococcaceae. The consortium adapted well with high glycerol
concentration of 120 g/L as well as wide substrate concentration fluctuation from
15 to 80 g/L, producing 60.61 and 82.66 g/L 1,3-PDO in the batch and fed-batch
fermentation, with the productivity of 3.79 and 3.06 g/(L?h), respectively, which
are among the best results published so far. Furthermore, mini consortia isolated
by serial dilution exhibited similar microbial composition but gradually
decreasing tolerance to crude glycerol. Four randomly selected Clostridium
butyricum displayed different substrate tolerance and insufficient 1,3-PDO
production capacity. This work demonstrated that the high adaptation to crude
glycerol of the consortium was the collaborative effort of different individuals.
PMID- 28512678
TI - Benefits of Long-Term Digital Support Following Bariatric Surgery Incorporating
Views from a Patient Advisory Group.
PMID- 28512676
TI - Different fermentation processes produced variants of an anti-CD52 monoclonal
antibody that have divergent in vitro and in vivo characteristics.
AB - The anti-CD52 antibody has already been approved for the treatment of patients
with resistant chronic lymphocytic leukemia, relapsing-remitting multiple
sclerosis, and has demonstrable efficacy against stem cell transplantation
rejection. A CHO cell line expressing a humanized anti-CD52 monoclonal antibody
(mAb-TH) was cultivated in both fed-batch and perfusion modes, and then purified.
The critical quality attributes of these mAb variants were characterized and the
pharmacokinetics (PK) properties were investigated. Results showed that the
perfusion culture achieved higher productivity, whereas the fed-batch culture
produced more aggregates and acid components. Additionally, the perfusion culture
produced similar fucose, more galactose and a higher proportion of sialic acid on
the anti-CD52 mAb compared to the fed-batch culture. Furthermore, the perfusion
process produced anti-CD52 mAb had higher complement-dependent cytotoxicity (CDC)
efficacy than that produced by the fed-batch culture, a result probably linked to
its higher galactose content. However, antibody produced by fed-batch and
perfusion cultures showed similar PK profiles in vivo. In conclusion, perfusion
is a more efficient method than fed-batch process in the production of functional
anti-CD52 monoclonal antibody. Product quality variants of anti-CD52 mAb were
found in different cell culture processes, which demonstrated different
physiochemical and biological activities, but comparable PK properties. Whether
these observations apply to all mAbs await further investigation.
PMID- 28512679
TI - Multiphysics Modeling of the Atrial Systole under Standard Ablation Strategies.
AB - The aim of this study was to develop a computational framework to compare the
impact of standard ablation concepts on the mechanical performance of the atria,
since different line combinations cannot be applied in practice to the same
patient. For this purpuse, we coupled electro-mechano-hemodynamic mathematical
models based on biophysical principles and simulate the contractile performance
of the atria. We computed systolic pressures and volumes in two patient-specific
atrial geometries (one of normal size and one hypertrophied) with various
ablation concepts. We found that our computational model is able to detect the
differences in the left atrial contractility and ejection fraction for various
electrical activation sequences resulting from different ablation line
combinations. We show that multiphysics modeling has the potential to quantify
the hemodynamic performance of left atria for different ablation lines, which
could be used as additional pre-operative clinical information for the choice of
the ablation concept in the future.
PMID- 28512680
TI - A Novel Idea to Improve Cardiac Output of Mechanical Circulatory Support Devices
by Optimizing Kinetic Energy Transfer Available in Forward Moving Aortic Blood
Flow.
AB - Mechanical circulatory support devices (MCSDs) have gained widespread clinical
acceptance as an effective heart failure (HF) therapy. The concept of harnessing
the kinetic energy (KE) available in the forward aortic flow (AOF) is proposed as
a novel control strategy to further increase the cardiac output (CO) provided by
MCSDs. A complete mathematical development of the proposed theory and its
application to an example MCSDs (two-segment extra-aortic cuff) are presented. To
achieve improved device performance and physiologic benefit, the example MCSD
timing is regulated to maximize the forward AOF KE and minimize retrograde flow.
The proof-of-concept was tested to provide support with and without KE control in
a computational HF model over a wide range of HF test conditions. The simulation
predicted increased stroke volume (SV) by 20% (9 mL), CO by 23% (0.50 L/min),
left ventricle ejection fraction (LVEF) by 23%, and diastolic coronary artery
flow (CAF) by 55% (3 mL) in severe HF at a heart rate (HR) of 60 beats per minute
(BPM) during counterpulsation (CP) support with KE control. The proposed KE
control concept may improve performance of other MCSDs to further enhance their
potential clinical benefits, which warrants further investigation. The next step
is to investigate various assist technologies and determine where this concept is
best applied. Then bench-test the combination of kinetic energy optimization and
its associated technology choice and finally test the combination in animals.
PMID- 28512681
TI - Evaluation of Immune Indices and Serum Vitamin D Content in Children with Atopic
Dermatitis.
AB - The influence of vitamin D on allergic diseases, including atopic dermatitis, is
linked to the presence of vitamin D nuclear receptors in immune cells. The
present study seeks to determine the possible relationship between serum vitamin
D content and immune indices in children with atopic dermatitis. The study was
conducted in 19 children with atopic dermatitis. The control consisted of 17 age
matched healthy children. A single significant finding was a distinctly lower
number of serum regulatory T cells in atopic dermatitis compared with controls (p
< 0.00001). There were no appreciable differences between the two groups
concerning the immunological indices such as the phenotypes: CD3, CD4, CD8,
CD4/CD8, CD19, CD16/56, natural killer T cells, and anti-CD3 human leukocyte
antigen - antigen D related cell surface receptor (HLA-DR3), or the percentage of
lymphocytes, eosinophils, and the IgE level. We also revealed an inverse
association between the serum vitamin D and the percentage of CD8+ cells (p <
0.05; r = 0.62) in atopic dermatitis. In conclusion, the results point to a
regulatory role of T cells in the pathogenesis of atopic dermatitis, but fail to
substantiate the influence of vitamin D on the course of the disease.
PMID- 28512682
TI - Causa formalis-detail matters.
PMID- 28512677
TI - Heterogeneity of proliferative markers in pancreatic beta-cells of patients with
severe hypoglycemia following Roux-en-Y gastric bypass.
AB - AIMS: Severe postprandial hypoglycemia with neuroglycopenia is an increasingly
recognized, debilitating complication of Roux-en-Y gastric bypass (RYGB) surgery.
Increased secretion of insulin and incretin hormones is implicated in its
pathogenesis. Histopathologic examination of pancreas has demonstrated increased
islet size and/or nuclear diameter in post-RYGB patients who underwent
pancreatectomy for severe refractory hypoglycemia with neuroglycopenia (RYGB +
NG). We aimed to determine whether beta-cell proliferation or apoptosis is
altered in RYGB + NG. METHODS: We performed an observational study to analyze
markers of proliferation, apoptosis, cell cycle, and transcription factor
expression in pancreatic tissue from affected RYGB + NG patients (n = 12),
normoglycemic patients undergoing pancreatic surgery for benign lesions
(controls, n = 6), and individuals with hypoglycemia due to insulinoma (n = 52).
RESULTS: Proliferative cell nuclear antigen (PCNA) expression was increased in
insulin-positive cells in RYGB + NG patients (4.5-fold increase, p < 0.001 vs.
controls) and correlated with beta-cell mass. Ki-67 immunoreactivity was low in
both RYGB + NG and controls, but did not differ between groups. Phospho-histone
H3 levels did not differ between RYGB + NG and controls. PCNA and Ki-67 were both
significantly lower in both controls and RYGB + NG than insulinomas. Markers of
apoptosis and cell cycle (M30, p27, and p21) did not differ between groups. PDX1
and menin exhibited similar expression patterns, while FOXO1 appeared to be more
cytosolic in RYGB + NG. CONCLUSIONS: Markers of proliferation are heterogeneous
in patients with severe post-RYGB hypoglycemia. Increased beta-cell proliferation
in some individuals may contribute to increased beta-cell mass observed in
severely affected patients.
PMID- 28512684
TI - Therapeutic Applications of Classic Hallucinogens.
AB - This chapter reviews what is known about the therapeutic uses of the serotonergic
or classic hallucinogens, i.e., psychoactive drugs such as LSD and psilocybin
that exert their effects primarily through agonist activity at serotonin 2A
(5HT2A) receptors. Following a review of the history of human use and scientific
study of these drugs, the data from clinical research are summarized, including
extensive work on the use of classic hallucinogens in the treatment of alcoholism
and other addictions, studies of the use of LSD and psilocybin to relieve
distress concerning death, particularly in patients with advanced or terminal
cancer, and more limited data concerning the use of classic hallucinogens to
treat mood and anxiety disorders. A survey of possible mechanisms of clinically
relevant effects is provided. The well-established safety of classic
hallucinogens is reviewed. To provide a clinical perspective, case summaries are
provided of two individuals who received treatment in recent controlled trials of
psilocybin: one being treated for alcoholism, the other suffering from anxiety
and depression related to fear of death due to a cancer diagnosis. Although
promising early phase research conducted from the 1950s through the early 1970s
was discontinued before firm conclusions could be reached concerning the efficacy
of any of the classic hallucinogens for any clinical condition, the research that
was conducted in that era strongly suggests that classic hallucinogens have
clinically relevant effects, particularly in the case of LSD treatment of
alcoholism. In the past decade, clinical trials have resumed investigating the
effects of classic hallucinogens in the treatment of existential distress in the
face of cancer, and in the treatment of addictions including alcoholism and
nicotine addiction. The studies that have been completed to date are not
sufficient to establish efficacy, but the outcomes have been very encouraging,
and larger trials, up to and including phase 3, are now underway or being
planned. Although research has elucidated many of the acute neurobiological and
psychological effects of classic hallucinogens on humans, animals, and in vitro
systems, the mechanisms of clinically relevant persisting effects remain poorly
understood.
PMID- 28512683
TI - Messenger RNA transport in the opportunistic fungal pathogen Candida albicans.
AB - Candida albicans, a common commensal fungus, can cause disease in
immunocompromised hosts ranging from mild mucosal infections to severe
bloodstream infections with high mortality rates. The ability of C. albicans
cells to switch between a budding yeast form and an elongated hyphal form is
linked to pathogenicity in animal models. Hyphal-specific proteins such as cell
surface adhesins and secreted hydrolases facilitate tissue invasion and host cell
damage, but the specific mechanisms leading to asymmetric protein localization in
hyphae remain poorly understood. In many eukaryotes, directional cytoplasmic
transport of messenger RNAs that encode asymmetrically localized proteins allows
efficient local translation at the site of protein function. Over the past two
decades, detailed mechanisms for polarized mRNA transport have been elucidated in
the budding yeast Saccharomyces cerevisiae and the filamentous fungus Ustilago
maydis. This review highlights recent studies of RNA-binding proteins in C.
albicans that have revealed intriguing similarities to and differences from known
fungal mRNA transport systems. I also discuss outstanding questions that will
need to be answered to reach an in-depth understanding of C. albicans mRNA
transport mechanisms and the roles of asymmetric mRNA localization in polarized
growth, hyphal function, and virulence of this opportunistic pathogen.
PMID- 28512686
TI - Amygdala structure and core dimensions of the affective personality.
AB - While biological models of human personality propose that socio-affective traits
and skills are rooted in the structure of the amygdala, empirical evidence
remains sparse and inconsistent. Here, we used a comprehensive assessment of the
affective personality and tested its association with global, local, and
laterality measures of the amygdala structure. Results revealed three broad
dimensions of the affective personality that were differentially related to
bilateral amygdala structures. Dysfunctional and maladaptive affective traits
were associated with a global size and local volume reduction of the amygdala,
whereas adaptive emotional skills were linked to an increased size of the left
amygdala. Furthermore, reduced asymmetry in the bilateral global amygdala volume
was linked to higher affective instability and might be a potential precursor of
psychiatric disorders. This study demonstrates that structural amygdala measures
provide a neural basis for all major dimensions of the human personality related
to adaptive and maladaptive socio-affective functioning.
PMID- 28512685
TI - Modeling brain lentiviral infections during antiretroviral therapy in AIDS.
AB - Understanding HIV-1 replication and latency in different reservoirs is an ongoing
challenge in the care of patients with HIV/AIDS. A mathematical model was created
to describe and predict the viral dynamics of HIV-1 and SIV infection within the
brain during effective combination antiretroviral therapy (cART). The
mathematical model was formulated based on the biology of lentiviral infection of
brain macrophages and used to describe the dynamics of transmission and
progression of lentiviral infection in brain. Based on previous reports
quantifying total viral DNA levels in brain from HIV-1 and SIV infections,
estimates of integrated proviral DNA burden were made, which were used to
calibrate the mathematical model predicting viral accrual in brain macrophages
from primary infection. The annual rate at which susceptible brain macrophages
become HIV-1 infected was estimated to be 2.90*10-7-4.87*10-6 per year for cART
treated HIV/AIDS patients without comorbid neurological disorders. The
transmission rate for SIV infection among untreated macaques was estimated to be
5.30*10-6-1.37*10-5 per year. An improvement in cART effectiveness (1.6-48%)
would suppress HIV-1 infection in patients without neurological disorders. Among
patients with advanced disease, a substantial improvement in cART effectiveness
(70%) would eradicate HIV-1 provirus from the brain within 3-32 (interquartile
range 3-9) years in patients without neurological disorders, whereas 4-51
(interquartile range 4-16) years of efficacious cART would be required for
HIV/AIDS patients with comorbid neurological disorders. HIV-1 and SIV provirus
burdens in the brain increase over time. A moderately efficacious antiretroviral
therapy regimen could eradicate HIV-1 infection in the brain that was dependent
on brain macrophage lifespan and the presence of neurological comorbidity.
PMID- 28512688
TI - Perceptions of Exercise During Medical School.
PMID- 28512687
TI - Added Value of Covered Stents in Transjugular Intrahepatic Portosystemic Shunt: A
Large Single-Center Experience.
AB - PURPOSE: Transjugular intrahepatic portosystemic shunts (TIPS) were historically
placed using uncovered bare-metal stents. Current practice has now shifted toward
the use of polytetrafluoroethylene (PTFE)-covered stents, given the improved
primary patency seen with these stents. The aim of this study was to determine
whether there is any added value, such as overall survival or stent patency, when
using covered stents versus uncovered stents in TIPS placement in a large cohort.
MATERIALS AND METHODS: From April 1995 to June 2012, a total of 744 consecutive
adult patients underwent de novo TIPS placement (378 receiving uncovered stents,
366 receiving covered stents). Information was obtained on demographics, baseline
clinical variables, and outcomes after TIPS placement. Data were collected,
compared, and analyzed to assess outcomes including mortality, primary patency
(determined via repeat intervention), and secondary patency (determined via
ultrasound parameters). RESULTS: Covered stents were associated with
significantly improved primary patency (P < 0.001) and secondary patency (P <
0.001) when compared with uncovered stents in TIPS procedures. Additionally,
covered stents were associated with higher estimated overall survival rates and
higher survival rates when TIPS was performed emergently and in patients with
higher Model for End-Stage Liver Disease (MELD) scores. For example, in patients
with MELD scores between 11 and 18, there was a predicted survival of 59.2% with
covered stents versus 42.8% with uncovered stents at 1 year. CONCLUSION: This
study demonstrated that covered stents offer the additional value of higher
estimated overall survival and higher estimated survival in patients undergoing
TIPS emergently and in those with higher MELD scores when compared to uncovered
stents.
PMID- 28512689
TI - Long-term results of fibular-Achilles tenodesis (Westin's tenodesis) for
paralytic pes calcaneus: is hypercorrection avoidable? A longitudinal
retrospective study.
AB - PURPOSE: The purpose of this study was to review all cases of patients submitted
to Westin's tenodesis, who had calcaneus feet secondary to myelomeningocele
sequel, in order to evaluate the anatomical change provided by surgery and also
to verify, in a long-term follow-up, the inversion of the deformity depending on
the patient's age. METHODS: In this longitudinal retrospective study, all medical
records of patients with myelomeningocele sequelae submitted to Westin's
tenodesis from 1993 to 2013 in a public university hospital were reviewed.
Patients were contacted for new clinical and radiographic evaluations after a
minimum of 36 months after surgery. The calcaneotibial angle was measured and the
shortening of the fibula was calculated as the "intermalleolar height". RESULTS:
The study was based on 16 children (26 feet), aged 84.27 months on average at the
time of tenodesis. The calcaneotibial angle increased significantly post
operatively, from 63.77 degrees on average to 70.54 degrees. Intermalleolar
height and valgus ankle did not change significantly. Most patients had
plantigrade feet after surgery, without pressure ulcers, and were able to use
orthoses. CONCLUSION: Westin's tenodesis, with or without other associated
procedures, can correct or improve the calcaneus and valgus ankle deformity in
patients with myelomeningocele sequelae. There was no association of the surgical
result with age at the time of surgery. There was no inversion of the deformity
in equinus during the follow-up time.
PMID- 28512690
TI - Translational studies on a ready-to-use intramuscular injection of penethamate
for bovine mastitis.
AB - Bovine mastitis caused by bacterial infections of the mammary gland (udder) of
dairy cows is a costly pathology for the dairy industry due to direct and
indirect losses in production. Penethamate, a pro-drug of benzylpenicillin, is
used by intramuscular injection (IM). The existing products are powders which
must be reconstituted in water-for-injection and this presents difficulties in
the field. Penethamate is too unstable to be formulated as an aqueous formulation
but a chemically stable suspension formulation was possible in certain oils;
however, some literature suggests that such formulations would have unacceptable
prolonged release. The translational research proceeded iteratively from lab to
the target species, rather than via laboratory animal trials. Pilot studies in
cows suggested that some oily suspensions would give concentrations of
benzylpenicillin, (in both blood and milk) comparable with those of the
reconstituted product. A physicochemical screen and a low level in vitro-in vivo
correlation (IVIVC) was cautiously used to guide selection of formulations for
subsequent animal trials which have resulted in a lead formulation for good
laboratory practices (GLP), good clinical practices (GCP) studies.
PMID- 28512691
TI - Complete Circumferential Osseous Extension in the Acetabular Rim Occurs
Regardless of Acetabular Coverage.
AB - BACKGROUND: Complete circumferential osseous extension in the acetabular rim has
been reported to occur in the deep hip with pincer impingement. However, this
phenomenon occasionally is observed in dysplastic hips without pincer
impingement, and the degree to which this finding might or might not be
associated with hip pain, and how often it occurs bilaterally among patients, are
not well characterized. QUESTIONS/PURPOSES: (1) To determine the proportion of
patients with complete circumferential osseous extension in the acetabular rim
using three-dimensional (3-D) CT in patients with and without hip pain who had CT
scans obtained for various reasons. (2) To elucidate how often this complete
circumferential osseous extension occurred bilaterally among those patients. (3)
To investigate the relationship between the proportions of patients with complete
circumferential osseous extension observed on CT scans among three different
acetabular coverage groups: dysplasia, normal, and overcoverage. (4) To determine
how often the finding of hip pain was associated with complete circumferential
osseous extension. PATIENTS AND METHODS: Between September 2011 to July 2016, we
evaluated 3788 patients with pelvic complaints such as hip, groin, thigh,
buttock, or sacroiliac joint pain. We obtained consent from 26% (992 of 3788) of
them, and obtained 3-D CT scans as part of that evaluation. For the current
retrospective study, we excluded patients younger than 20 years or 80 years or
older (181 patients), patients who had previous hip surgery (185 patients),
patients with severe osteoarthritis with Tonnis Grades 2 or 3 (301 patients), and
patients who could not have an accurate lateral center-edge (LCE) angle measured
owing to poor-quality radiographs (24 patients), leaving 301 patients (602 hips)
for this analysis. In this study population, patients reported pain in 131 hips
(22%), defined as all types of hip pain except for trauma, including activity
pain, pain with sports, pain on motion, and impingement pain; the others did not
report hip pain. The mean age of the patients was 56 +/- 16 years, and the mean
LCE angle was 26 degrees +/- 8 degrees (range, -9 degrees to 47 degrees ). We
first determined the proportion of patients with complete circumferential osseous
extension in the acetabular rim using 3-D CT for those with and without hip pain
who had CT obtained for various reasons. We next elucidated how often this
complete circumferential osseous extension occurred bilaterally among the
patients, and finally we investigated the relationship between the proportion of
patients with complete circumferential osseous extension observed on CT scans
among the three groups: dysplasia (defined as LCE angles of 22 degrees or
smaller), normal, and overcoverage (defined as LCE angles of 34 degrees or
larger) groups. We finally determined how often the finding was associated with
hip pain attributable to complete circumferential osseous extension. RESULTS: The
proportion of patients with complete circumferential osseous extension was 6% (18
of 301 patients). Eighty-nine percent (16 of 18) of the patients had bilateral
complete circumferential osseous extension. There were no differences in the
proportions of patients with complete circumferential osseous extension among the
three groups: 5.3% (odds ratio [OR], 1.02; 95% CI, 0.45-2.31; p = 0.97), 5.3%,
and 7.4% (OR, 0.70; 95% CI, 0.28-1.73; p = 0.44) in the dysplasia, normal, and
overcoverage groups, respectively, with the numbers available. Eighteen percent
(six of 34) of the hips with complete circumferential osseous extension had pain.
CONCLUSIONS: Complete circumferential osseous extension in the acetabular rim is
relatively uncommon. When it occurs, it usually is bilateral, it occurs
regardless of acetabular coverage, and it is associated with pain in a minority
of patients. LEVEL OF EVIDENCE: Level III, prognostic study.
PMID- 28512694
TI - Erratum to: Pregnancy Outcomes Following In Utero Exposure to Lamotrigine: A
Systematic Review and Meta-Analysis.
PMID- 28512696
TI - Synthesis, Characterization, Electrochemical and Surface Morphologies of
Polyazomethines Containing Silane and Phosphazene Units.
AB - Polyazomethines containing silane and phosphazene groups were synthesized via
elimination reactions of dihydroxy compounds containing imine bonding with
phosphazane and silane dichloride. The structures of monomers and polymers
containing phosphazane and silane groups were supported by 1H-NMR, 13C-NMR, FT-IR
and UV-Vis techniques. Electrochemical properties of the prepared Schiff bases
and polymers were given by cyclic voltammetric (CV) analysis. Thermal properties
of synthesized monomers and polymers were determined by TG-DTA and TG-DTA, DMA
and DSC techniques, respectively. Molecular mass distributions of polymers are
determined with gel permeation chromatography (GPC) measurement. Morphologic
images of polymers containing heteroatom (silane/phosphazene) and azomethine
linkage in the main chain were investigated by SEM techniques. The
electrochemical band gap values of SB-1, SB-2, P-1, P-2 and P-3 compounds were
found as 3.09, 3.30, 2.63, 3.07 and 3.04 eV, respectively.
PMID- 28512692
TI - Virtual Reality-Enhanced Extinction of Phobias and Post-Traumatic Stress.
AB - Virtual reality (VR) refers to an advanced technological communication interface
in which the user is actively participating in a computer-generated 3-dimensional
virtual world that includes computer sensory input devices used to simulate real
world interactive experiences. VR has been used within psychiatric treatment for
anxiety disorders, particularly specific phobias and post-traumatic stress
disorder, given several advantages that VR provides for use within treatment for
these disorders. Exposure therapy for anxiety disorder is grounded in fear
conditioning models, in which extinction learning involves the process through
which conditioned fear responses decrease or are inhibited. The present review
will provide an overview of extinction training and anxiety disorder treatment,
advantages for using VR within extinction training, a review of the literature
regarding the effectiveness of VR within exposure therapy for specific phobias
and post-traumatic stress disorder, and limitations and future directions of the
extant empirical literature.
PMID- 28512695
TI - Arsenic Induces Thioredoxin 1 and Apoptosis in Human Liver HHL-5 Cells.
AB - To further characterize the mechanisms underlying liver toxicity induced by
arsenic, we examined in this study the effect of arsenic on thioredoxin (Trx) and
the apoptotic signaling pathways in human liver HHL-5 cells. The cells were
treated with 0, 2, 5, and 10 MUM of sodium arsenite for 24 h, and the changes of
Trx1 and thioredoxin reductase (TrxR1) as well as intracellular ROS and apoptosis
were examined. A concentration-dependent increase in mRNA and protein levels of
Trx1 and TrxR1 was observed in arsenic-treated cells. Intracellular ROS levels
and apoptosis were also significantly increased in a concentration-dependent
manner. In line with this, protein levels of Bax and cytochrome C were increased
and Bcl-2 was decreased by arsenic treatments. Increases in caspase 3 activity
were observed. These results indicate that Trx is involved in arsenic-induced
liver cell injury, probably through the apoptotic signaling pathway. However,
further studies are needed to elucidate on these findings.
PMID- 28512697
TI - Utilization of Genetic Counseling after Direct-to-Consumer Genetic Testing:
Findings from the Impact of Personal Genomics (PGen) Study.
AB - Direct-to-consumer personal genomic testing (DTC-PGT) results lead some
individuals to seek genetic counseling (GC), but little is known about these
consumers and why they seek GC services. We analyzed survey data pre- and post
PGT from 1026 23andMe and Pathway Genomics customers. Participants were mostly
white (91%), female (60%), and of high socioeconomic status (80% college
educated, 43% household income of >=$100,000). After receiving PGT results, 43
participants (4%) made or planned to schedule an appointment with a genetic
counselor; 390 (38%) would have used in-person GC had it been available. Compared
to non-seekers, GC seekers were younger (mean age of 38 vs 46 years), more
frequently had children <18 (26% vs 16%), and were more likely to report previous
GC (37% vs 7%) and genetic testing (30% vs 15%). In logistic regression analysis,
seeking GC was associated with previous GC use (OR = 6.5, CI = 3.1-13.8), feeling
motivated to pursue DTC-PGT for health reasons (OR = 4.3, CI = 1.8-10.1), fair or
poor self-reported health (OR = 3.1, CI = 1.1-8.3), and self-reported uncertainty
about the results (OR = 1.8, CI = 1.1-2.7). These findings can help GC providers
anticipate who might seek GC services and plan for clinical discussions of DTC
PGT results.
PMID- 28512698
TI - Repair of the pronator quadratus after volar plate fixation in distal radius
fractures: a systematic review.
AB - To position the volar plate on the distal radius fracture site, the pronator
quadratus muscle needs to be detached from its distal and radial side and lifted
for optimal exposure to the fracture site. Although the conventional approach
involves repair of the pronator quadratus, controversy surrounds the merits of
this repair. The purpose of this study was to compare the functional outcomes of
patients with distal radius fractures treated with pronator quadratus repair
after volar plate fixation versus no pronator quadratus repair. A systematic
search was conducted in Medline, EMBASE and the Cochrane Central Register of
Controlled Trials, on 23 July 2015. All studies comparing pronator quadratus
repair with no pronator quadratus repair in adult patients undergoing volar plate
fixation for distal radius fractures were included. The primary outcome was the
Disability of the Arm, Shoulder and Hand (DASH) score at 12 months. Secondary
outcomes included range of motion, grip strength, post-operative pain and
complications. A total of 169 patients were included, of which 95 underwent
pronator quadratus repair, while 74 patients underwent no pronator quadratus
repair. At 12 months follow-up no statistically significant differences in DASH
scores and range of motion were observed between pronator quadratus repair and no
repair. Moreover, post-operative pain and complication rates were similar between
both groups. At 12 months of follow-up, we do not see any advantages of pronator
quadratus repair after volar plate fixation in the distal radius. However, a
definitive conclusion cannot be drawn from this systematic review due to a lack
of available evidence.
PMID- 28512700
TI - Use of insulin glargine and cancer incidence in Scotland: a study from the
Scottish Diabetes Research Network Epidemiology Group.
PMID- 28512699
TI - An Open-Label Crossover Study of the Pharmacokinetics of the 60-mg Edoxaban
Tablet Crushed and Administered Either by a Nasogastric Tube or in Apple Puree in
Healthy Adults.
AB - BACKGROUND: Edoxaban is an orally active, direct factor Xa inhibitor indicated to
reduce the risk of stroke and systemic embolism in non-valvular atrial
fibrillation and for the treatment of venous thromboembolism. OBJECTIVES: This
study assessed the pharmacokinetics, safety, and tolerability of the edoxaban 60
mg tablet crushed and administered via a nasogastric tube in a water suspension
or orally mixed in apple puree. METHODS: This phase 1, open-label, crossover
study randomized 30 healthy adults to receive three edoxaban treatment regimens
(oral 60-mg edoxaban tablet, or 60-mg edoxaban tablet crushed and administered
via a nasogastric tube or orally in apple puree) in one of six treatment
sequences. RESULTS: Total edoxaban exposure was similar between the intact and
crushed tablet regimens (mean area under the plasma concentration-time curve from
time zero to infinity: whole tablet, 2132 ng.h/mL; nasogastric tube, 2021
ng.h/mL; apple puree, 2076 ng.h/mL). Mean maximum plasma concentration, area
under the plasma concentration-time curve from time zero to the time of the last
measurable concentration, terminal half-life, and apparent total body clearance
values were also similar. Time to maximum plasma concentration was significantly
shorter for the nasogastric tube suspension and apple puree vs. the whole tablet
[Hodges-Lehmann estimate of median difference (90% confidence interval): -0.75 (
1.25, -0.28); p = 0.0003 and -0.62 (-0.99, -0.26); p = 0.0024, respectively]. The
maximum plasma concentation, area under the plasma concentration-time curve from
time zero to infinity, and area under the plasma concentration-time curve from
time zero to the time of the last measurable concentration were similar between
treatment regimens; 90% confidence interval of the geometric least-squares means
ratios were within the predefined 80-125% bioequivalence criterion. The safety
and tolerability of edoxaban did not differ between treatment regimens.
CONCLUSION: The results support the use of edoxaban tablets crushed and
administered either via a nasogastric tube or orally mixed in apple puree in
patients who are unable to swallow solid oral dose formulations.
PMID- 28512701
TI - Estimation of 3D Ground Reaction Force Using Nanocomposite Piezo-Responsive Foam
Sensors During Walking.
AB - This paper describes a method for the estimation of the 3D ground reaction force
(GRF) during human walking using novel nanocomposite piezo-responsive foam (NCPF)
sensors. Nine subjects (5 male, 4 female) walked on a force-instrumented
treadmill at 1.34 m/s for 120 s each while wearing a shoe that was instrumented
with four NCPF sensors. GRF data, measured via the treadmill, and sensor data,
measured via the NCPF inserts, were used in a tenfold cross validation process to
calibrate a separate model for each individual. The calibration model estimated
average anterior-posterior, mediolateral and vertical GRF with mean average
errors (MAE) of 6.52 N (2.14%), 4.79 N (6.34%), and 15.4 N (2.15%), respectively.
Two additional models were created using the sensor data from all subjects and
subject demographics. A tenfold cross validation process for this combined data
set resulted in models that estimated average anterior-posterior, mediolateral
and vertical GRF with less than 8.16 N (2.41%), 6.63 N (7.37%), and 19.4 N
(2.31%) errors, respectively. Intra-subject estimates based on the model had a
higher accuracy than inter-subject estimates, likely due to the relatively small
subject cohort used in creating the model. The novel NCPF sensors demonstrate the
ability to accurately estimate 3D GRF during human movement outside of the
traditional biomechanics laboratory setting.
PMID- 28512702
TI - An Intracardiac Soft Robotic Device for Augmentation of Blood Ejection from the
Failing Right Ventricle.
AB - We introduce an implantable intracardiac soft robotic right ventricular ejection
device (RVED) for dynamic approximation of the right ventricular (RV) free wall
and the interventricular septum (IVS) in synchrony with the cardiac cycle to
augment blood ejection in right heart failure (RHF). The RVED is designed for
safe and effective intracardiac operation and consists of an anchoring system
deployed across the IVS, an RV free wall anchor, and a pneumatic artificial
muscle linear actuator that spans the RV chamber between the two anchors. Using a
ventricular simulator and a custom controller, we characterized ventricular
volume ejection, linear approximation against different loads and the effect of
varying device actuation periods on volume ejection. The RVED was then tested in
vivo in adult pigs (n = 5). First, we successfully deployed the device into the
beating heart under 3D echocardiography guidance (n = 4). Next, we performed a
feasibility study to evaluate the device's ability to augment RV ejection in an
experimental model of RHF (n = 1). RVED actuation augmented RV ejection during
RHF; while further chronic animal studies will provide details about the efficacy
of this support device. These results demonstrate successful design and
implementation of the RVED and its deployment into the beating heart. This soft
robotic ejection device has potential to serve as a rapidly deployable system for
mechanical circulatory assistance in RHF.
PMID- 28512703
TI - Metal homeostasis in bacteria: the role of ArsR-SmtB family of transcriptional
repressors in combating varying metal concentrations in the environment.
AB - Bacterial infections cause severe medical problems worldwide, resulting in
considerable death and loss of capital. With the ever-increasing rise of
antibiotic-resistant bacteria and the lack of development of new antibiotics,
research on metal-based antimicrobial therapy has now gained pace. Metal ions are
essential for survival, but can be highly toxic to organisms if their
concentrations are not strictly controlled. Through evolution, bacteria have
acquired complex metal-management systems that allow them to acquire metals that
they need for survival in different challenging environments while evading metal
toxicity. Metalloproteins that controls these elaborate systems in the cell, and
linked to key virulence factors, are promising targets for the anti-bacterial
drug development. Among several metal-sensory transcriptional regulators, the
ArsR-SmtB family displays greatest diversity with several distinct metal-binding
and nonmetal-binding motifs that have been characterized. These prokaryotic
metolloregulatory transcriptional repressors represses the expression of operons
linked to stress-inducing concentrations of metal ions by directly binding to the
regulatory regions of DNA, while derepression results from direct binding of
metal ions by these homodimeric proteins. Many bacteria, e.g., Mycobacterium
tuberculosis, Bacillus anthracis, etc., have evolved to acquire multiple metal
sensory motifs which clearly demonstrate the importance of regulating
concentrations of multiple metal ions. Here, we discussed the mechanisms of how
ArsR-SmtB family regulates the intracellular bioavailability of metal ions both
inside and outside of the host. Knowledge of the metal-challenges faced by
bacterial pathogens and their survival strategies will enable us to develop the
next generation drugs.
PMID- 28512704
TI - Pseudomonas aeruginosa Inhibits the Growth of Scedosporium and Lomentospora In
Vitro.
AB - In vitro bacterial-fungal interaction studies in cystic fibrosis (CF) have mainly
focused on interactions between bacteria and Candida. Here we investigated the
effect of Pseudomonas aeruginosa on the growth of Scedosporium/Lomentospora spp.
Standard suspensions of P. aeruginosa (16 non-mucoid and nine mucoid isolates)
were dropped onto paper disks, placed on lawns of Lomentospora prolificans
(formerly Scedosporium prolificans) strain WM 14.140 or Scedosporium aurantiacum
strain WM 11.78 on solid agar. The median inhibitory activity (mIz) was
calculated for each fungal-bacterial combination. As a group, mIz values for non
mucoid phenotype P. aeruginosa strains were significantly lower than those for
mucoid strains (P < 0.001); 14/16 (87.5%) non-mucoid strains had mIz <1.0 against
both fungi versus just 3/9 mucoid strains (33.4%) (P = 0.01). One non-mucoid
(PA14) and one mucoid (CIDMLS-PA-28) P. aeruginosa strain effecting inhibition
were selected for further studies. Inhibition of both L. prolificans and S.
aurantiacum by these strains was confirmed using the XTT (2,3-bis(2-methoxy-4
nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide)
reduction assay. Following incubation with XTT, inhibition of fungal growth was
determined as the ratio of absorbance in liquid culture with Pseudomonas to that
in control fungal cultures. An absorbance ratio of <1.0 consistent with bacterial
inhibition of fungal growth was observed for all four P. aeruginosa-fungal
combinations (P < 0.05). Fluorescence microscopy, subsequent to co-culture of
either fungal isolate with P. aeruginosa strain PA14 or CIDMLS-PA-28 revealed
poorly formed hyphae, compared with control fungal cultures. P. aeruginosa
inhibits growth of L. prolificans and S. aurantiacum in vitro, with non-mucoid
strains more commonly having an inhibitory effect. As P. aeruginosa undergoes
phenotype transitions from non-mucoid to the mucoid form with progression of CF
lung disease, this balance may influence the appearance of Scedosporium fungi in
the airways.
PMID- 28512705
TI - Predicting fecal coliform using the interval-to-interval approach and SWAT in the
Miyun watershed, China.
AB - Pathogens in manure can cause waterborne-disease outbreaks, serious illness, and
even death in humans. Therefore, information about the transformation and
transport of bacteria is crucial for determining their source. In this study, the
Soil and Water Assessment Tool (SWAT) was applied to simulate fecal coliform
bacteria load in the Miyun Reservoir watershed, China. The data for the fecal
coliform were obtained at three sampling sites, Chenying (CY), Gubeikou (GBK),
and Xiahui (XH). The calibration processes of the fecal coliform were conducted
using the CY and GBK sites, and validation was conducted at the XH site. An
interval-to-interval approach was designed and incorporated into the processes of
fecal coliform calibration and validation. The 95% confidence interval of the
predicted values and the 95% confidence interval of measured values were
considered during calibration and validation in the interval-to-interval
approach. Compared with the traditional point-to-point comparison, this method
can improve simulation accuracy. The results indicated that the simulation of
fecal coliform using the interval-to-interval approach was reasonable for the
watershed. This method could provide a new research direction for future model
calibration and validation studies.
PMID- 28512707
TI - Geochemistry and sources of fluoride and nitrate contamination of groundwater in
Lar area, south Iran.
AB - Groundwater quality in bone-dry and semiarid areas of Iran is decreasing because
of contaminants from natural origins and anthropogenic sources. Among many
harmful contaminants, nitrate and fluoride ions are more common. This study was
carried out with the aim of determining geochemical processes controlling
chemistry of groundwater with special reference to nitrate and fluoride
enrichment in groundwater in Lar plain aquifer, south of Iran. Groundwater
samples were collected from 17 sites and analyzed for main constituents (Na, K,
Ca, Mg, Cl, SO42-, HCO3-, F-, and NO3-). Composite diagram, saturation indices
calculation, and multivariate analysis techniques including cluster and factor
analyses were employed in evaluating groundwater quality. The EC ranges from
8793.87 to 13,345.00 MUS/cm in wet season and from 9621.59 to 12,640.00 MUS/cm in
dry season. Fluoride amounts range between 0.59 and 3.92 mg/L. Nitrate
concentrations range between 1.47 and 70.66 mg/L. Results indicate that
dissolution-precipitation of carbonate and evaporate minerals, evaporation (in
terms of agricultural water return), and opposite ion interchange are the main
processes that determine groundwater chemistry. It seems that fluoride has a
natural origin and the equilibrium reaction between fluorite and calcite is very
significant to control fluoride concentration level in water. Vertical variation
of nitrate concentration and distribution of agricultural areas have indicated
that nitrate originated from nitrogenous inorganic fertilizers used during
irrigation periods. The results also indicate that denitrification takes place in
the aquifer and that nitrate decline is not only a function of dilution but also
a process of denitrification.
PMID- 28512706
TI - Cyanides in the environment-analysis-problems and challenges.
AB - Cyanide toxicity and their environmental impact are well known. Nevertheless,
they are still used in the mining, galvanic and chemical industries. As a result
of industrial activities, cyanides are released in various forms to all elements
of the environment. In a natural environment, cyanide exists as cyanogenic
glycosides in plants seeds. Too much consumption can cause unpleasant side
effects. However, environmental tobacco smoke (ETS) is the most common source of
cyanide. Live organisms have the ability to convert cyanide into less toxic
compounds excreted with physiological fluids. The aim of this paper is to review
the current state of knowledge on the behaviour of cyanide in the environment and
its impact on the health and human life.
PMID- 28512709
TI - Influence of low-temperature combustion and dimethyl ether-diesel blends on
performance, combustion, and emission characteristics of common rail diesel
engine: a CFD study.
AB - Due to presence of more oxygen, absence of carbon-carbon (C-C) bond in chemical
structure, and high cetane number of dimethyl ether (DME), pollution from DME
operated engine is less compared to diesel engine. Hence, the DME can be a
promising alternative fuel for diesel engine. The present study emphasizes the
effect of various exhaust gas recirculation (EGR) rates (0-20%) and DME/Diesel
blends (0-20%) on combustion characteristics and exhaust emissions of common rail
direct injection (CRDI) engine using three-dimensional computational fluid
dynamics (CFD) simulation. Extended coherent flame model-3 zone (ECFM-3Z) is
implemented to carry out combustion analysis, and k-xi-f model is employed for
turbulence modeling. Results show that in-cylinder pressure marginally decreases
with employing EGR compared to without EGR case. As EGR rate increases, nitrogen
oxide (NO) formation decreases, whereas soot increases marginally. Due to better
combustion characteristics of DME, indicated thermal efficiency (ITE) increases
with the increases in DME/diesel blend ratio. Adverse effect of EGR on efficiency
for blends is less compared to neat diesel, because the anoxygenated region
created due to EGR is compensated by extra oxygen present in DME. The trade-off
among NO, soot, carbon monoxide (CO) formation, and efficiency is studied by
normalizing the parameters. Optimum operating condition is found at 10% EGR rate
and 20% DME/diesel blend. The maximum indicated thermal efficiency was observed
for DME/diesel ratio of 20% in the present range of study. Obtained results are
validated with published experimental data and found good agreement.
PMID- 28512708
TI - Titanium dioxide-based sonophotocatalytic mineralization of bisphenol A and its
intermediates.
AB - In this study, bisphenol A (BPA) removal by sonophotocatalysis coupled with
commercially available titanium dioxide (TiO2, P25) was assessed in batch tests
using energy-based advanced oxidation combining ultrasound (US) and ultraviolet
(UV). The kinetics of BPA removal were systematically evaluated by changing
operational parameters, such as US frequency and power, mechanical stirring
speed, and temperature, but also comparison of single and coupled systems under
the optimum US conditions (35 kHz, 50 W, 300 rpm stirring speed, and 20 degrees
C). The combination of US/UV/P25 exhibited the highest BPA removal rate (28.0 *
10-3 min-1). In terms of the synergy index, the synergistic effect of
sonophotocatalysis was found to be 2.2. This indicated that sonophotocatalysis
has a considerably higher removal efficiency than sonocatalysis or
photocatalysis. The removal of BPA was further investigated to identify BPA
byproducts and intermediates using high-performance liquid chromatography-mass
spectrometry. Five main intermediates were formed during sonophotocatalytic
degradation, and complete removal of BPA and its intermediates was obtained after
3 h of operation. The degradation pathway of BPA by sonophotocatalysis was also
elucidated.
PMID- 28512711
TI - Environmental Kuznets curve for EU agriculture: empirical evidence from new
entrant EU countries.
AB - The present work examines the intertemporal causal relationship between
environmental damage from carbon emissions released by agriculture per 1000 ha of
utilized agriculture area and economic performance in the sector of agriculture
as described by net value added per capita. The autoregressive distributed lag
bounds testing approach is employed to examine this linkage, for three new
entrant EU countries, namely, Bulgaria, Czech Republic, and Hungary. The
environmental Kuznets hypothesis is confirmed in the long run for Bulgaria and
Czech Republic while in the short run is validated only for the case of Czech
Republic. The results indicate that the adoption of environment-friendly farming
practices and crops' selection does not secure simultaneous high economic and
environmental performance at least in the short run for our sample countries and
also in the long run for Hungary necessitating the modification of the agro
environmental measures adopted to make those two targets complementary and not
mutually exclusive for a farmer.
PMID- 28512710
TI - Effects of coexisting BDE-47 on the migration and biodegradation of BDE-99 in
river-based aquifer media recharged with reclaimed water.
AB - Two prominent polybrominated diphenyl ether (PBDE) congeners have been included
in the persistent organic pollutant list, 2,2',4,4',5-tetrabromodiphenyl ether
(BDE-99) and 2,2,4,4'-tetrabromodiphenyl ether (BDE-47), which have been detected
in treated municipal wastewater, river water, and sediments in China. A lab-scale
column experiment was established to investigate the effects of the competitive
sorption of BDE-47 on BDE-99 biodegradation and migration in two types of river
based aquifer soils during groundwater recharge with reclaimed water. Two types
of recharge columns were used, filled with either silty clay (SC) or black carbon
amended silty clay (BCA). The decay rate constants of BDE-99 in the BCA and SC
systems were 0.186 and 0.13 m-1 in the single-solute system and 0.128 and 0.071 m
1 in the binary-solute system, respectively, showing that the decay of BDE-99 was
inhibited by the coexistence of BDE-47. This was particularly evident in the SC
system because the higher hydrophobicity of BDE-99 determined the higher affinity
and competition for sorption sites onto black carbon. The biodegradation of BDE
99 was suppressed by the coexistence of BDE-47, especially in the SC system.
Lesser-brominated congeners (BDE-47 and BDE-28) and higher-brominated congeners
(BDE-100, BDE-153, BDE-154, and BDE-183) were generated in the four recharge
systems, albeit at different ratios. Bacterial biodiversity was influenced by the
presence of BDE-47 in the SC system, while it had no significant effect on the
BCA system, because the high sorption capacity of black carbon on the hydrophobic
PBDEs effectively reduced their toxicity. The ranking order of the most abundant
classes changed markedly due to the coexistence of BDE-47 in both the SC and BCA
systems. The ranking order of the most abundant genera changed from Azospira,
Methylotenera, Desulfovibrio, Methylibium, and Bradyrhizobium to Halomonas,
Hyphomicrobium, Pseudomonas, Methylophaga, and Shewanella, which could be
involved in PBDE degradation.
PMID- 28512712
TI - Post-Translational Tubulin Modifications in Human Astrocyte Cultures.
AB - The cytoskeletal protein tubulin plays an integral role in the functional
specialization of many cell types. In the central nervous system, post
translational modifications and the expression of specific tubulin isotypes in
neurons have been analyzed in greater detail than in their astrocytic
counterparts. In this study, we characterized post-translational specifications
of tubulin in human astrocytes using the normal human astrocyte (NHA; Lonza)
commercial cell line of fetal origin. Immunocytochemical techniques were
implemented in conjunction with confocal microscopy to image class III beta
tubulin (betaIII-tubulin), acetylated tubulin, and polyglutamylated tubulin using
fluorescent antibody probes. Fluorescent probe intensity differences and
colocalization were quantitatively assessed with the 'EBImage' package for the
statistical programming language R. Colocalization analysis revealed that,
although both acetylated tubulin and polyglutamylated tubulin showed a high
degree of correlation with betaIII-tubulin, the correlation with acetylated
tubulin was stronger. Quantification and statistical analysis of fluorescence
intensity demonstrated that the fluorescence probe intensity ratio for acetylated
tubulin/betaIII-tubulin was greater than the ratio for polyglutamylated
tubulin/betaIII-tubulin. The open source GEODATA set GSE819950, comprising RNA
sequencing data for the NHA cell line, was mined for the expression of enzymes
responsible for tubulin modifications. Our analysis uncovered greater expression
at the mRNA level for enzymes reported to function in acetylation and
deacetylation as compared to enzymes implicated in glutamylation and
deglutamylation. Taken together, the results represent a step toward unraveling
the tubulin isotypic expression profile and post-translational modification
patterns in astrocytes during human brain development.
PMID- 28512713
TI - Matairesinol Suppresses Neuroinflammation and Migration Associated with Src and
ERK1/2-NF-kappaB Pathway in Activating BV2 Microglia.
AB - Chronic neuroinflammation is a pathological feature of neurodegenerative
diseases. Inhibition of microglia-mediated neuroinflammation might be a potential
strategy for neurodegeneration. Matairesinol, a dibenzylbutyrolactone plant
lignan, presents in a wide variety of foodstuffs. It has been found to possess
anti-angiogenic, anti-oxidative, anti-cancer and anti-fungal activities. In the
present study, we investigated the anti-neuroinflammation effects of matairesinol
on lipopolysaccharide (LPS)-induced BV2 microglia cells and the related molecular
mechanisms. The results showed that matairesinol inhibited microglia activation
by reducing the production of nitric oxide, the expression of inducible nitric
oxide synthase and cyclooxygenase-2 in a concentration-dependent manner (6.25,
12.5, 25 MUM). In the molecular signaling pathway, LPS-induced nuclear factor
kappa B (NF-kappaB) transcriptional activity and translocation into the nucleus
were remarkably suppressed by matairesinol through the inhibition of the
extracellular signal-regulated kinase (ERK)1/2 signal transduction pathways, but
not p38 MAPK or c-jun N-terminal kinase (JNK). Meanwhile, matairesinol also
blocked LPS-mediated microglia migration and this was associated with inhibition
of LPS-induced Src phosphorylation as well as Src expression in a concentration
dependent manner. Taken together, these results suggest that matairesinol
inhibited inflammatory response and migration in LPS-induced BV2 microglia, and
the mechanisms may be associated with the NF-kappaB activation and modulation of
Src pathway.
PMID- 28512715
TI - Management of rainwater harvesting and its impact on the health of people in the
Middle East: case study from Yatta town, Palestine.
AB - Water-related diseases are a primary problem in Palestine where many residents
revert to harvested rainwater as their primary water source due to water
shortages within the area. From an environmental engineering perspective, it is
already well known that certain situations (e.g., cross contamination) reduce
drinking water quality and ultimately cause diseases in a population. In this
study, we investigated the social practices and situations that may lead to lower
disease occurrence. Towards this goal, we surveyed 382 residents in Yatta to
collect data on the water-related diseases that they experienced and the specific
situations that might affect the disease occurrences such as the residents'
practices (i) for maintaining a high quality of cistern water, (ii) for
maintaining the environment around the cistern, and (iii) for managing the
wastewater. In addition, we measured the physicochemical and microbiological
parameters in cisterns to support the qualitative survey data. The measured
parameters, including turbidity, salinity, free available chlorine, total
Coliforms, and fecal Coliforms, were above Palestinian Standard Institution (PSI)
and World Health Organization (WHO) guideline levels, suggesting a potential
infectious hazard. The poor quality of the water was also observed by residents
based on change in taste and by visually noting floating impurities, turbidity,
and green coloration. Survey results showed that observations of the poor quality
in cisterns and surrounding environment had statistically significant correlation
with most of the water-related diseases. Additionally, frequently emptying the
septic tank contributes to improving the observed water qualities. Therefore,
residents should be encouraged to continue to observe the water quality in the
cistern, improve the surrounding environment of cistern, and empty their septic
tank frequently, to keep the water diseases away from their households.
PMID- 28512716
TI - Clint M. Alfaro wins ABC Best Paper Award.
PMID- 28512714
TI - Comparison of the diagnostic accuracy of PET/MRI to PET/CT-acquired FDG brain
exams for seizure focus detection: a prospective study.
AB - BACKGROUND: There is great interest in positron emission tomography
(PET)/magnetic resonance (MR) as a clinical tool due to its capacity to provide
diverse diagnostic information in a single exam. OBJECTIVE: The goal of this exam
is to compare the diagnostic accuracy of PET/MR-acquired [F-18]2-fluoro-2
deoxyglucose (FDG) brain exams to that of PET/CT with respect to identifying
seizure foci in children with localization-related epilepsy. MATERIALS AND
METHODS: Institutional Review Board approval and informed consent were obtained
for this Health Insurance Portability and Accountability Act-compliant,
prospective study. All patients referred for clinical FDG-PET/CT exams of the
brain at our institution for a diagnosis of localization-related epilepsy were
prospectively recruited to undergo an additional FDG-PET acquisition on a tandem
PET/MR system. Attenuation-corrected FDG images acquired at PET/MR and PET/CT
were interpreted independently by five expert readers. Readers were blinded to
the scanner used for acquisition and attenuation correction as well as all other
clinical and imaging data. A Likert scale scoring system (1-5) was used to assess
image quality. The locale of seizure origin determined at multidisciplinary
epilepsy surgery work rounds was considered the reference standard. Non
inferiority testing for paired data was used to compare the diagnostic accuracy
of PET/MR to that of PET/CT. RESULTS: The final study population comprised 35
patients referred for a diagnosis of localization-related epilepsy (age range: 2
19 years; median: 11 years; 21 males, 14 females). Image quality did not differ
significantly between the two modalities. The accuracy of PET/MR was not inferior
to that of PET/CT for localization of a seizure focus (P=0.017). CONCLUSION: The
diagnostic accuracy of FDG-PET images acquired on a PET/MR scanner and generated
using MR-based attenuation correction was not inferior to that of PET images
processed by traditional CT-based correction.
PMID- 28512717
TI - Infrared laser ablation sample transfer of tissue DNA for genomic analysis.
AB - Infrared (IR) laser ablation was used to remove material from tissue sections
mounted on microscope slides, with subsequent capture in a solvent-containing
microcentrifuge tube. Experiments conducted with a 3200-bp double-stranded
plasmid DNA template demonstrated IR-laser ablation transfer of intact DNA. The
transfer efficiency and the molecular integrity of the captured DNA were
evaluated using Sanger sequencing, gel electrophoresis, and fluorimetric
analysis. The plasmid DNA was reproducibly transferred with an efficiency of 59
+/- 3% at laser fluences of between 10 and 20 kJ/m2 at a wavelength of 3 MUm. IR
laser ablation sample transfer was then used to ablate and capture DNA from 50
MUm-thick rat brain and kidney tissue sections. DNA was extracted from the
captured material using five commercial DNA extraction kits that employed
significantly divergent methodologies, with all kits recovering sufficient DNA
for successful amplification by polymerase chain reaction (PCR). Four sets of
primers were employed, targeting one region of the CYP 11b2 gene (376 bp) and
three different regions of the Snn1g gene (298, 168, and 281 bp). The PCR results
were not consistently reliable when using unpurified ablation samples; however,
after extraction, all samples produced PCR products of the expected size. This
work expands the sampling capabilities of IR laser ablation, demonstrating that
DNA can be isolated from tissue samples for genomic assays. Due to the small size
of the ablation regions (1 mm2), this technique will be useful for sampling
discrete cell populations from tissue sections. Graphical abstract Infrared laser
ablation transfer of intact DNA from a tissue section.
PMID- 28512718
TI - Development of In Vitro-In Vivo Correlation for Potassium Chloride Extended
Release Tablet Formulation Using Urinary Pharmacokinetic Data.
AB - PURPOSE: To develop and validate a Level A in vitro-in vivo correlation (IVIVC)
for potassium chloride extended-release (ER) formulations. METHODS: Three
prototype ER formulations of potassium chloride with different in vitro release
rates were developed and their urinary pharmacokinetic profiles were evaluated in
healthy subjects. A mathematical model between in vitro dissolution and in vivo
urinary excretion, a surrogate for measuring in vivo absorption, was developed
using time-scale and time-shift parameters. The IVIVC model was then validated
based on internal and external predictability. RESULTS: With the established
IVIVC model, there was a good correlation between the observed fraction of dose
excreted in urine and the time-scaled and time-shifted fraction of the drug
dissolved, and between the in vitro dissolution time and the in vivo urinary
excretion time for the ER formulations. The percent prediction error (%PE) on
cumulative urinary excretion over the 24 h interval (Ae0-24h) and maximum urinary
excretion rate (Rmax) was less than 15% for the individual formulations and less
than 10% for the average of the two formulations used to develop the model.
Further, the %PE values using external predictability were below 10%.
CONCLUSIONS: A novel Level A IVIVC was successfully developed and validated for
the new potassium chloride ER formulations using urinary pharmacokinetic data.
This successful IVIVC may facilitate future development or manufacturing changes
to the potassium chloride ER formulation.
PMID- 28512719
TI - Hypoplastic Left Heart Syndrome with Congenital Complete Heart Block.
AB - Congenital complete atrioventricular block (CCAVB) is a rare condition with an
incidence of 1 of 20,000 live births. Hypoplastic left heart syndrome (HLHS)
occurs more frequently than CCAVB and occurs in 1 of 5000 live births. HLHS in
association with CCAVB is exceedingly rare. In this report, we describe a rare
case of HLHS and CCAVB diagnosed in utero. Postnatal diagnosis, management and
outcome are presented as well as review of the medical literature.
PMID- 28512720
TI - Pacing Induced Ventricular Dysfunction in a Child: Improvement with Reduction in
Paced Rate.
AB - Right ventricular (RV) pacing can be associated with impairment of left
ventricular (LV) function due to electrical dyssynchrony and myocardial
remodeling (Janousek et al. in J Cardiovasc Electrophysiol 15:470-474, 2004). RV
pacing induced ventricular dysfunction is reversible by techniques such as
biventricular pacing and LV apical or LV free wall pacing or turning the
pacemaker off which have all been shown to restore synchrony and improve left
ventricular function (Janousek et al. in J Cardiovasc Electrophysiol 15:470-474,
2004; Geldorp et al. in Heart Fail Rev 16:305-314, 2011). We describe an infant
with RV-pacing induced cardiomyopathy who improved when the pacing rate was
reduced thus demonstrating the relationship between pacing rate and development
of LV dysfunction.
PMID- 28512721
TI - Mid-term Risk for Subclinical Atherosclerosis and Chronic Myocarditis in Children
with Kawasaki Disease and Transient Coronary Abnormalities.
AB - There is evidence for premature atherosclerosis and systemic arterial stiffening
during follow-up of children with Kawasaki disease (KD) and coronary artery
abnormalities (CAA). Moreover, patients with KD may also have subclinical
myocardial involvement and inhomogeneous ventricular repolarization. The
inhomogeneous ventricular repolarization manifests as increased QT dispersion on
electrocardiography. There is a paucity of studies in endothelial dysfunction and
QT dispersion in children with KD and transient CAA. Twenty children with KD and
transient CAA were studied at least 1 year after resolution of CAA. Mean follow
up period between KD onset and enrolment in the study was 53.7 months. Twenty age
and sex-matched controls were enrolled. High-resolution B-mode ultrasonography
was used to analyze brachial artery dilatation in response to reactive hyperemia
(cases and controls) and sublingual nitroglycerine (cases only). Carotid artery
intima-media thickness (cIMT) and stiffness index were calculated. The difference
between maximum and minimum QTc intervals on 12 lead electrocardiogram was
calculated as QTc dispersion (QTcd). No statistically significant difference was
noted in percent flow-mediated dilatation of brachial arteries in response to
reactive hyperemia between cases (13.31 +/- 10.41%) and controls (12.86 +/-
7.09%). Sublingual nitroglycerine-mediated dilatation in children with KD was
14.88 +/- 12.03%. Mean cIMT was similar in cases (0.036 +/- 0.015 cm) and
controls (0.035 +/- 0.076 cm; p = 0.791). No statistically significant difference
between groups was observed in mean QTcd values (0.057 +/- 0.018 s vs. 0.059 +/-
0.015 s in controls, p = 0.785). No evidence of significant endothelial
dysfunction or increased QT dispersion in patients with KD and transient coronary
artery abnormalities was found in our cohort when studied at a mean follow-up of
53.7 months. This is reassuring, and indicates that risk of subclinical
atherosclerosis and myocarditis in a subset of children with KD and transient
coronary artery abnormalities is not significant.
PMID- 28512722
TI - Status of cardiovascular PET radiation exposure and strategies for reduction: An
Information Statement from the Cardiovascular PET Task Force.
AB - Cardiovascular positron emission tomography (PET) imaging provides high-quality
visual and quantitative myocardial perfusion and function images. In addition,
cardiovascular PET can assess myocardial viability, myocardial inflammatory
disorders such as cardiac sarcoid, and infections of implanted devices including
pacemakers, ventricular assist devices, and prosthetic heart valves. As with all
nuclear cardiology procedures, the benefits need to be considered in relation to
the risks of exposure to radiation. When performed properly, these assessments
can be obtained while simultaneously minimizing radiation exposure. The purpose
of this information statement is to present current concepts to minimize patient
and staff radiation exposure while ensuring high image quality.
PMID- 28512723
TI - Low-dose dual-isotope procedure planed for myocardial perfusion CZT-SPECT and
assessed through a head-to-head comparison with a conventional single-isotope
protocol.
AB - PURPOSE OF THE REPORT: This study aimed at assessing an original low-dose dual
isotope procedure in which the abnormal stress Tc-99m Sestamibi SPECT is followed
by rest Tl-201 SPECT, along with a head-to-head comparison with a single-isotope
procedure. METHODS AND RESULTS: One hundred two patients, referred for a low-dose
stress-SPECT with Sestamibi (123 +/- 20 MBq) on a CZT camera and for whom a rest
Sestamibi SPECT was warranted, had an additional Tl-201 rest-SPECT (52 +/- 5 MBq)
between stress and rest Sestamibi SPECT recordings. Tl-201 images were processed
for spill-over and scatter corrections, and uptake differences with stress
Sestamibi SPECT were analyzed: (1) for rest acquisitions from Tl-201 (dual
isotope procedure) and from Sestamibi (single-isotope procedure) and (2) in
segments for which a diagnosis of ischemia, infarct, or normal perfusion was
achieved. Mean effective dose was 8.3 mSv for dual-isotope but would decrease to
5.7 mSv for an expected rate of 37% of patients for whom rest-SPECT is not
warranted. After a further background correction of Tl-201 images, the rest
stress difference in myocardial uptake was equivalent between dual- and single
procedures for identifying ischemic segments (respective areas-under-curves: 0.83
+/- 0.03 and 0.81 +/- 0.03). CONCLUSION: This original dual-isotope procedure
provides acceptable radiation doses and consistent results, as compared with
conventional single-isotope.
PMID- 28512724
TI - Congenital Pulmonary Alveolar Proteinosis: From Birth to Ten-years of Age.
AB - Pulmonary alveolar proteinosis is a rare lung disease in which lipoproteinaceous
material accumulates within the alveoli, interfering with gas exchange. The
disease is classified into congenital, secondary, and acquired. The congenital
form includes inborn errors of surfactant metabolism, lysinuric protein
intolerance and mutations in the components of granulocyte-macrophage colony
stimulating factor receptor. The main symptoms are non-specific. The radiologic
appearance of pulmonary alveolar proteinosis is bilateral, symmetric and
perihilar airspace consolidation. Bronchoalveolar lavage is crucial for diagnosis
of the disease. There is only one ten-year-old patient with diagnosed congenital
form in Croatia. What makes him different from other children in the world is
that since the ninth month of his life he has been mechanically ventilated.
Diagnosis of postnatal alveolar proteinosis should be considered in every infant
with respiratory distress with diffuse alveolar and interstitial infiltrate.
PMID- 28512725
TI - Clofibrate as an Adjunct to Phototherapy for Unconjugated Hyperbilirubinemia in
Term Neonates.
AB - OBJECTIVE: To evaluate the efficacy of oral clofibrate as an adjunct to
phototherapy for unconjugated hyperbilirubinemia in term neonates. METHODS: This
randomized controlled trial was done in the level III neonatal intensive care
unit (NICU) of a tertiary care hospital. Ninety term neonates with unconjugated
hyperbilirubinemia with serum bilirubin 15-25 mg/dl were randomized to either
intervention group (single dose of clofibrate in a dose of 50 mg/kg prior to
starting phototherapy) or standard care group (only phototherapy). Primary
outcome was absolute fall in bilirubin by 48 h. Secondary outcomes were duration
of phototherapy, absolute fall in bilirubin levels at 12, 24, 36, 48 h, need for
exchange transfusion and incidence of side-effects. RESULTS: After 48 h of
intervention, significantly lower bilirubin levels were noted in the intervention
group compared to standard care group with a mean difference of 7 mg/dl (95% CI
6.7 mg/dl to 7.2 mg/dl). Duration of phototherapy required was less in the
intervention group compared to standard care group with mean difference of 23.82
h (95% CI 30.46 h to 17.18 h). Exchange transfusion was needed for 4 neonates in
the standard care group and none in the intervention group. No side-effects were
noted with clofibrate. CONCLUSIONS: Single dose clofibrate prior to starting
phototherapy in term neonates with uncomplicated unconjugated hyperbilirubinemia
reduces the duration of phototherapy significantly.
PMID- 28512726
TI - Cutaneous reflex modulation during obstacle avoidance under conditions of normal
and degraded visual input.
AB - The nervous system integrates visual input regarding obstacles with limb-based
sensory feedback to allow an individual to safely negotiate the environment. This
latter source can include cutaneous information from the foot, particularly in
the event that limb trajectory is not sufficient and there is an unintended
collision with the object. However, it is not clear the extent to which cutaneous
reflexes are modified based on visual input. In this study, we first determined
if phase-dependent modulation of these reflexes is present when stepping over an
obstacle during overground walking. We then tested the hypothesis that degrading
the quality of visual feedback alters cutaneous reflex amplitude in this task.
Subjects walked and stepped over an obstacle-leading with their right foot-while
we electrically stimulated the right superficial peroneal nerve at the level of
the ankle at different phases. Subjects performed this task with normal vision
and with degraded vision. We found that the amplitude of cutaneous reflexes
varied based on the phase of stepping over the obstacle in all leg muscles
tested. With degraded visual feedback, regardless of phase, we found larger
facilitation of cutaneous reflexes in the ipsilateral biceps femoris-a muscle
responsible for flexing the knee to avoid the obstacle. Although degrading vision
caused minor changes in several other muscles, none of these differences reached
the level of significance. Nonetheless, our results suggest that visual feedback
plays a role in altering how the nervous system uses other sensory input in a
muscle-specific manner to ensure safe obstacle clearance.
PMID- 28512728
TI - Treatment of red tattoo reaction using CO2 laser.
PMID- 28512727
TI - Variability of high-dose melphalan exposure on oral mucositis in patients
undergoing prophylactic low-level laser therapy.
AB - The present study outlines the clinical impact and risk factors of oral mucositis
in 79 patients with multiple myeloma following high-dose melphalan for autologous
transplant. All patients underwent daily prophylactic low-level indium gallium
aluminum phosphate diode laser therapy (660 nm, 15 mW, 3.75 J/cm2, 10 s per
point) from the beginning of the conditioning regimen up to day +2. Oral
mucositis assessments were made daily until hospital discharge. For analysis,
oral mucositis was divided into two groups according to severity: group 1,
patients with oral mucositis grade =III (n = 8). Univariate logistic models were used to determine
the risk factors. Patients in group 1 were found to have statistically fewer days
of oral pain than those in group 2 (3.94 and 6.25 days, respectively, p = 0.014).
Morphine was required in 75% of patients in group 2, versus 42.25% in group 1 (p
= 0.06). Risk of severe oral mucositis was associated with higher serum
creatinine levels (OR = 6.10; 95% CI 1.25-31.60; p = 0.02) and older age (OR =
1.21; 95% CI 1.05-1.47; p = 0.027). Severe oral mucositis was associated with
worse clinical outcomes. Older patients and those with renal dysfunction previous
autologous transplant had the greatest risk for severe oral mucositis despite
prophylactic laser treatment. Our results highlight the importance of further
research to define the dose, application time, and number of prophylactic laser
sessions in those patients with the greatest risk for severe oral mucositis.
PMID- 28512731
TI - Active Surveillance for Prostate Cancer: How to Do It Right.
AB - Prostate cancer is the most common malignancy affecting men. There has been a
nearly 70% increase in new prostate cancer cases, mostly classified as low risk,
that have been diagnosed in early stages as a consequence of prostate-specific
antigen (PSA) screening. Data regarding the natural history of this disease
confirm the clinical insignificance of low-grade prostate cancer, which is
associated with scant or no metastatic dissemination. Active surveillance is a
conservative management approach, conducted for those patients with "low-risk" or
"favorable-risk" disease, which avoids long-term adverse effects on the patient's
quality of life. It is characterized by a routine protocol of close monitoring
with digital rectal examination, periodic biopsy, and serial PSA testing. As
defined by D'Amico, active surveillance is broadly appropriate for men with a
Gleason score of 6 or less and a PSA level of less than 10 ng/mL. Typically,
Gleason pattern 3 disease lacks the common genetic aberrancies of a true cancer.
An essential element of the active surveillance approach is early recognition of
higher-risk disease, which is diagnosed by systematic biopsy in 30% of patients
who initiate active surveillance with low-risk disease. Also, a small group of
patients have molecular alterations that can cause progression to more aggressive
disease; these men can be switched to immediate treatment if such progression is
detected. Oncologic outcomes for active surveillance cohorts have shown the long
term safety of this approach, with a cancer-specific mortality rate of 3% at 10
to 15 years. In this review of active surveillance for favorable-risk prostate
cancer, we will discuss the rationality of this approach, the biological evidence
for employing active surveillance in Gleason pattern 3 and 4 prostate cancer,
patient selection for active surveillance, clinical trial data on active
surveillance, and the role of prostate cancer biomarkers and imaging studies
(MRI) for clinical decision making in patients with low-risk disease.
PMID- 28512730
TI - Examining the Role of Transmission of Chelonid Alphaherpesvirus 5.
AB - Marine turtle fibropapillomatosis (FP) is a devastating neoplastic disease
characterized by single or multiple cutaneous and visceral fibrovascular tumors.
Chelonid alphaherpesvirus 5 (ChHV5) has been identified as the most likely
etiologic agent. From 2010 to 2013, the presence of ChHV5 DNA was determined in
apparently normal skin, tumors and swab samples (ocular, nasal and cloacal)
collected from 114 olive ridley (Lepidochelys olivacea) and 101 green (Chelonia
mydas) turtles, with and without FP tumors, on the Pacific coasts of Costa Rica
and Nicaragua. For nesting olive ridley turtles from Costa Rica without FP, 13.5%
were found to be positive for ChHV5 DNA in at least one sample, while in
Nicaragua, all olive ridley turtles had FP tumors, and 77.5% tested positive for
ChHV5 DNA. For green turtles without FP, 19.8% were found to be positive for
ChHV5 DNA in at least one of the samples. In turtles without FP tumors, ChHV5 DNA
was detected more readily in skin biopsies than swabs. Juvenile green turtles
caught at the foraging site had a higher prevalence of ChHV5 DNA than adults. The
presence of ChHV5 DNA in swabs suggests a possible route of viral transmission
through viral secretion and excretion via corporal fluids.
PMID- 28512729
TI - Protective effects of Nebivolol against interleukin-1beta (IL-1beta)-induced type
II collagen destruction mediated by matrix metalloproteinase-13 (MMP-13).
AB - The pathological progression of osteoarthritis (OA) involves degradation of
articular cartilage matrix. Type II collagen is the main component of cartilage
matrix, which is degraded by pro-inflammatory cytokines such as IL-1beta mediated
by MMP-13. Nebivolol, a licensed drug used for the treatment of hypertension in
clinics, displays its anti-inflammatory capacity in various conditions. However,
whether Nebivolol has a protective effect on cartilage matrix degradation has not
been reported before. In this study, we investigated the effects of Nebivolol on
regulating the expression of MMP-13 and degradation of type II collagen. Our
results indicate that Nebivolol alleviated the increase in gene expression,
protein expression, and activity of MMP-13 induced by IL-1beta. Importantly, IL
1beta strikingly reduced the levels of type II collagen in cell culture
supernatants, which was reversed by treatment with Nebivolol in a dose-dependent
manner. Mechanistically, Nebivolol was found to alleviate the increased levels of
phosphorylated IkappaBalpha and reduced levels of total IkappaBalpha induced by
IL-1beta, which subsequently mitigated p65 nuclear translocation and the
transcriptional activity of NF-kappaB. Furthermore, our results indicated that IL
1beta treatment resulted in a significant increase in expression of the
transcriptional factor interferon regulatory factor-1 (IRF-1) at both the mRNA
and protein levels, which was significantly ameliorated by treatment with
Nebivolol. The combination of these findings suggests that Nebivolol can
potentially be applied in human OA treatment.
PMID- 28512732
TI - Decision Making in the Surgical Management of Invasive Breast Cancer-Part 1:
Lumpectomy, Mastectomy, and Contralateral Prophylactic Mastectomy.
AB - Several prospective randomized clinical trials conducted internationally have
proven the safety and survival equivalence of breast-conserving surgery compared
with mastectomy. Adjuvant radiation is routinely recommended following lumpectomy
surgery to minimize the risk of local recurrence. Comprehensive breast imaging
(including bilateral mammography with diagnostic views and ultrasound
evaluation), in addition to clinical examination, is essential to rule out
potential contralateral pathology and to optimally characterize the extent of
disease. These studies are considered standard in the assessment of patient
eligibility for lumpectomy. MRI of the breast remains controversial as an adjunct
to determine candidacy for breast conservation, since MRI findings increase
mastectomy rates without evidence of improved local control; prospective
randomized clinical trials are underway to define the role of MRI in newly
diagnosed breast cancer. Recently, the multidisciplinary oncology community has
adopted a consensus guideline defining "no ink on tumor" as an acceptable
microscopic margin at lumpectomy; however, post-lumpectomy imaging may be
necessary to confirm complete removal of all cancer-associated
microcalcifications, with clinical judgment exercised regarding re-excision for
close margins. Contralateral prophylactic mastectomy is becoming increasingly
common in the United States, and patients considering this option must be
counseled about its lack of a survival benefit, its higher complication rate, and
the fact that it is risk-reducing but not risk-eliminating.
PMID- 28512733
TI - A lipidomic cell-based assay for studying drug-induced phospholipidosis and
steatosis.
AB - Phospholipidosis and steatosis are two toxic effects, which course with
overaccumulation of different classes of lipids in the liver. MS-based lipidomics
has become a powerful tool for the comprehensive determination of lipids. LC-MS
lipid profiling of HepG2 cells is proposed as an in vitro assay to study and
anticipate phospholipidosis and steatosis. Cells with and without preincubation
with a mixture of free fatty acids (FFA; i.e. oleic and palmitic) were exposed to
a set of well-known steatogenic and phospholipidogenic compounds. The use of FFA
preloading accelerated the accumulation of phospholipids, thus leading to a
better discrimination of phospholipidosis, and magnified the lipidomic
alterations induced by steatogenic drugs. Phospholipidosis was characterized by
increased levels of phosphatidylcholines, phosphatidylethanolamines,
phosphatidylserines, and phosphatidylinositols, while steatosis induced
alterations in FA oxidation and triacylglyceride (TG) synthesis pathways (with
changes in the levels of FFA, acylcarnitines, monoacylglycerides,
diacylglycerides, and TG). Interestingly, palmitic and oleic acids incorporation
into lipids differed. A characteristic pattern was observed in the fold of change
of particular TG species in the case of steatosis (TG(54:3) > TG(52:2) > TG(50:1)
> TG(48:0)). Based on the levels of those lipids containing only palmitic and/or
oleic acid moieties a partial least squares-discriminant analysis model was
built, which showed good discrimination among nontoxic, phospholipidogenic and
steatogenic compounds. In conclusion, it has been shown that the use of FFA
preincubation together with intracellular LC-MS based lipid profiling could be a
useful approach to identify the potential of drug candidates to induce
phospholipidosis and/or steatosis.
PMID- 28512734
TI - Mitral valve aneurysms: Clinical characteristics, echocardiographic
abnormalities, and possible mechanisms of formation.
AB - AIMS: Mitral valve aneurysms (MVA) are most frequently associated with
endocarditis. Echocardiography is the method of choice for diagnosis, and color
flow imaging is an important, easy method to detect MVA ruptures. We aimed to
study the clinical and echocardiographic findings and their relation to the
mechanism of aneurysm formation. METHODS AND RESULTS: We reviewed clinical and
echocardiographic records of 18 patients during a 17-year period, corresponding
to 0.02% of the total studies performed at our institution. All patients
underwent transthoracic echocardiogram (TTE), and all except two underwent
transesophageal echocardiogram (TEE). The aneurysm was located either on the
anterior leaflet (16 cases) or on the posterior leaflet (two cases). In seven
cases, the probable aneurysm formation mechanism was an aortic regurgitant jet
striking the anterior mitral leaflet. Perforation was present in 17 (94.4%)
patients, and 10 (55.5%) cases presented more than one aneurysm. No patients
underwent surgery exclusively because of the echocardiography finding.
CONCLUSION: Different etiologies and formation mechanisms can occur in MVA.
Echocardiography plays a fundamental role, providing meticulous examination of
the mitral valve anatomy and flow. Unlike standard recommendations, clinical
management is possible, and diagnosis does not imply immediate surgical
correction.
PMID- 28512735
TI - Fluorinated Porous Conjugated Polyporphyrins through Direct C-H Arylation
Polycondensation: Preparation, Porosity, and Use as Heterogeneous Catalysts for
Baeyer-Villiger Oxidation.
AB - By considering the high reactivity of fluorinated iron-porphyrin and good
stability of porphyrin-based porous polymers, fluorinated iron-porphyrin
conjugated porous polymers (FPOP-3-6) were synthesized through direct C-H
arylation polymerization. The obtained materials are chemically and thermally
stable, of which FPOP-3 exhibits the highest Brunauer-Emmett-Teller specific
surface area (about 840 m2 g-1 ). For functional studies of the obtained
polymers as heterogeneous catalysts, catalytic transformation of cycloketones
into lactones by oxygen through Baeyer-Villiger oxidation was used as a model
reaction. Fluorinated phenyl substituents of the iron-porphyrin not only are
beneficial to the conversion, but also can stabilize the porphyrin to resist
catalyst breakdown. The polymer FPOP-3, with high porosity, exhibits the best
catalytic efficiency and recycling effect. The recovered catalyst also shows good
catalytic activities after recycling three times with a small loss in yield.
PMID- 28512737
TI - Mucinous non-neoplastic cyst of the pancreas: is surgical resection avoidable?
PMID- 28512736
TI - CAGI4 SickKids clinical genomes challenge: A pipeline for identifying pathogenic
variants.
AB - Compared with earlier more restricted sequencing technologies, identification of
rare disease variants using whole-genome sequence has the possibility of finding
all causative variants, but issues of data quality and an overwhelming level of
background variants complicate the analysis. The CAGI4 SickKids clinical genome
challenge provided an opportunity to assess the landscape of variants found in a
difficult set of 25 unsolved rare disease cases. To address the challenge, we
developed a three-stage pipeline, first carefully analyzing data quality, then
classifying high-quality gene-specific variants into seven categories, and
finally examining each candidate variant for compatibility with the often complex
phenotypes of these patients for final prioritization. Variants consistent with
the phenotypes were found in 24 out of the 25 cases, and in a number of these,
there are prioritized variants in multiple genes. Data quality analysis suggests
that some of the selected variants are likely incorrect calls, complicating
interpretation. The data providers followed up on three suggested variants with
Sanger sequencing, and in one case, a prioritized variant was confirmed as likely
causative by the referring physician, providing a diagnosis in a previously
intractable case.
PMID- 28512738
TI - First-in-Class Composite Angiotensin Receptor-Neprilysin Inhibitors (ARNI) in
Practice.
AB - Sacubitril/valsartan, a first-in-class angiotensin receptor-neprilysin inhibitor
(ARNI) inhibits angiotensin II and neprilysin, enhancing circulating vasoactive
peptides. It is recommended in heart failure with reduced ejection fraction
(HFrEF) as a result of the PARADIGM-HF trial.1 This review discusses the
rationale for neprilysin inhibition, data supporting efficacy, and practical tips
for patient selection and utilization.
PMID- 28512739
TI - Normal development of spinal axons in early embryo stages and posterior locomotor
function is independent of GAL-1.
AB - It was recently described that Galectin-1 (Gal-1) promotes axonal growth after
spinal cord injury. This effect depends on protein dimerization, since monomeric
Gal-1 fails to stimulate axonal re-growth. Gal-1 is expressed in vivo at
concentrations that favor the monomeric species. The aim of the present study is
to investigate whether endogenous Gal-1 is required for spinal axon development
and normal locomotor behavior in mice. In order to characterize axonal
development, we used a novel combination of 3-DISCO technique with 1-photon
microscopy and epifluorescence microscopy under high power LED illumination,
followed by serial image section deconvolution and 3-D reconstruction. Cleared
whole lgals-1-/- embryos were used to analyze the 3-D cytoarchitecture of motor,
commissural, and sensory axons. This approach allowed us to evaluate axonal
development, including the number of fibers, fluorescence density of the fiber
tracts, fiber length as well as the morphology of axonal sprouting, deep within
the tissue. Gal-1 deficient embryos did not show morphological/anatomical
alterations in any of the axonal populations and parameters analyzed. In
addition, specific guidance receptor PlexinA4 did not change its axonal
localization in the absence of Gal-1. Finally, Gal-1 deficiency did not change
normal locomotor activity in post-natal animals. Taken together, our results show
that development of spinal axons as well as the locomotor abilities observed in
adult mice are independent of Gal-1. Supporting our previous observations, the
present study further validates the use of lgals-1-/- mice to develop spinal cord
or traumatic brain injury models for the evaluation of the regenerative action
of Gal-1.
PMID- 28512740
TI - Excited-state minima and emission energies of retinal chromophore analogues:
Performance of CASSCF and CC2 methods as compared with CASPT2.
AB - This study provides gas-phase S1 excited-state geometries along with emission and
adiabatic energies for methylated/demethylated and ring-locked analogues of
protonated Schiff base retinal models comprising system of five conjugated double
bonds (PSB5), using second order multiconfiguration perturbation theory (CASPT2).
CASPT2 results serve as reference data to assess the performance of CC2 (second
order approximate coupled cluster singles and doubles) and a commonly used
CASSCF/CASPT2 protocol, that is, complete active space self-consistent field
(CASSCF) geometry optimization followed by CASPT2 energy calculation. We find
that the CASSCF methodology fails to locate planar S1 minimum energy structures
for four out of five investigated planar models in contrast to CC2 and CASPT2
methods. However, for those which were found: one planar and two twisted minima,
there is an excellent agreement between CASSCF and CASPT2 results in terms of
geometrical parameters, one-electron properties, as well as emission and
adiabatic energies. CC2 performs well for in-plane S1 minima and their
spectroscopic and electronic properties. However, this picture deteriorates for
twisted minima. As expected, the CC2 description of the S2 electronic state, with
strong multireference and significant double excitation character, is very poor,
exhibiting errors in transition energies exceeding 1 eV. They may be
substantially diminished by recalculating transition energies with CASPT2 method.
Our work shows that CASSCF/CASPT2 and CC2 shortcomings may influence gas-phase
retinal analogues' excited state description in a dramatic way. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28512741
TI - Intervention for elevated intracranial pressure improves success rate after
repair of spontaneous cerebrospinal fluid leaks.
AB - OBJECTIVES/HYPOTHESIS: Spontaneous cerebrospinal fluid (CSF) leaks are associated
with increased intracranial pressure (ICP) and considered a manifestation of
idiopathic intracranial hypertension. Although postoperative acetazolamide and
placement of CSF shunt systems are considered valuable interventions for elevated
ICP, the impact on recurrence rate remains unclear. The objective of this study
was to systematically review evidence from reported literature to evaluate
whether postoperative ICP management reduces recurrence rates after primary
endoscopic repair. STUDY DESIGN: Prospective case series and systematic review.
METHODS: Demographics, defect location, success rates, and ICP management in
spontaneous CSF leak patients were prospectively collected over 8 years. A search
was also conducted in PubMed to identify studies reporting cases of spontaneous
CSF rhinorrhea. RESULTS: Fifty-six articles with nonduplicated data were
identified and combined with a prospective series of 108 patients for a total of
679 patients treated for spontaneous CSF rhinorrhea. Average age was 50.4 years
with 77% female. Average body mass index was 35.8 kg/m2 . Defects were most
commonly located in the sphenoid sinus (n = 334) followed by the ethmoid (n =
318) and the frontal sinus (n = 46). Successful primary repair was 92.82% in
patient cohorts where ICP evaluation and intervention with acetazolamide or CSF
shunt systems was performed, but was significantly decreased to 81.87% in series
with no active management of elevated ICP (P < .001). CONCLUSIONS: Evaluation and
intervention for elevated ICP in spontaneous CSF leaks is associated with
significantly improved success rates following primary endoscopic repair. LEVEL
OF EVIDENCE: 4. Laryngoscope, 127:2011-2016, 2017.
PMID- 28512742
TI - Differing intrinsic biological properties between forebrain and spinal
oligodendroglial lineage cells.
AB - Differentiation of oligodendroglial progenitor cells (OPCs) into myelinating
oligodendrocytes is known to be regulated by the microenvironment where they
differentiate. However, current research has not verified whether or not
oligodendroglial lineage cells (OLCs) derived from different anatomical regions
of the central nervous system (CNS) respond to microenvironmental cues in the
same manner. Here, we isolated pure OPCs from rat neonatal forebrain (FB) and
spinal cord (SC) and compared their phenotypes in the same in vitro conditions.
We found that although FB and SC OLCs responded differently to the same external
factors; they were distinct in proliferation response to mitogens,
oligodendrocyte phenotype after differentiation, and cytotoxic responses to alpha
amino-3-hydroxy-5-methyl-4-isoxazolepropionate-type glutamate receptor-mediated
excitotoxicity at immature stages of differentiation in a cell-intrinsic manner.
Moreover, transcriptome analysis identified genes differentially expressed
between these OPC populations, including those encoding transcription factors
(TFs), cell surface molecules, and signaling molecules. Particularly, FB and SC
OPCs retained the expression of FB- or SC-specific TFs, such as Foxg1 and Hoxc8,
respectively, even after serial passaging in vitro. Given the essential role of
these TFs in the regional identities of CNS cells along the rostrocaudal axis,
our results suggest that CNS region-specific gene regulation by these TFs may
cause cell-intrinsic differences in cellular responses between FB and SC OLCs to
extracellular molecules. Further understanding of the regional differences among
OPC populations will help to improve treatments for demyelination in different
CNS regions and to facilitate the development of stem cell-derived OPCs for cell
transplantation therapies for demyelination. Cover Image for this issue: doi.
10.1111/jnc.13809.
PMID- 28512743
TI - Proteinase 3-antineutrophil cytoplasmic antibody-associated cutaneous vasculitis
without systemic involvement.
PMID- 28512744
TI - Incremental benefit of three-dimensional transesophageal echocardiography in the
assessment of left main coronary artery stent protrusion.
AB - Ostial lesions represent a challenging clinical scenario and percutaneous
intervention (PCI) of left main coronary artery ostial lesions has been
associated with postintervention complications, including protrusion of deployed
stents into a sinus of Valsalva or aortic root. We report a case of stent
protrusion into the aortic root following aorto-ostial left main coronary artery
PCI, in which three-dimensional transesophageal echocardiography (3DTEE) provided
incremental benefit over standard two-dimensional images. Specifically, 3DTEE
confirmed the presence of stent protrusion by allowing clear visualization of the
stent scaffold, in addition to characterizing the relationship between the stent
and surrounding structures.
PMID- 28512745
TI - Implementation of multidisciplinary care reduces maternal mortality in women with
sickle cell disease living in low-resource setting.
AB - Sickle cell disease (SCD) is associated with adverse pregnancy outcome. In women
with SCD living in low-resource settings, pregnancy is associated with
significantly increased maternal and perinatal mortality rates. We tested the
hypothesis that implementing a multidisciplinary obstetric and hematology care
team in a low-resource setting would significantly reduce maternal and perinatal
mortality rates. We conducted a before-and-after study, at the Korle-Bu Teaching
Hospital in Accra, Ghana, to evaluate the effect of a multidisciplinary obstetric
hematology care team for women with SCD in a combined SCD-Obstetric Clinic. The
pre-intervention period was assessed through a retrospective chart review to
identify every death and the post-intervention period was assessed prospectively.
Interventions consisted of joint obstetrician and hematologist outpatient and
acute inpatient reviews, close maternal and fetal surveillance, and simple
protocols for management of acute chest syndrome and acute pain episodes. Primary
outcomes included maternal and perinatal mortality rates before and after the
study period. A total of 158 and 90 pregnant women with SCD were evaluated in the
pre- and post- intervention periods, respectively. The maternal mortality rate
decreased from 10 791 per 100 000 live births at pre-intervention to 1176 per 100
000 at post-intervention, representing a risk reduction of 89.1% (P = 0.007).
Perinatal mortality decreased from 60.8 per 1000 total births at pre-intervention
to 23.0 per 1000 at post-intervention, representing a risk reduction of 62.2% (P
= 0.20). A multidisciplinary obstetric and hematology team approach can
dramatically reduce maternal and perinatal mortality in a low-resource setting.
PMID- 28512747
TI - Visuoperceptual processing in children with neurofibromatosis type 1: True
deficit or artefact?
AB - Impairments in visuoperceptual processing have long been considered a hallmark
deficit of individuals with Neurofibromatosis type 1 (NF1). However, it is
unclear which specific visuoperceptual subprocesses are impaired and whether
impairments on these tasks really result from visuoperceptual impairments or
rather from confounding factors like Executive Functioning (EF) impairments,
lower intelligence (IQ) and/or co-occurring symptoms of Autism Spectrum Disorder
(ASD). To answer these questions, we administered four visuoperceptual tasks and
two control tasks in 39 children with NF1, 52 typically developing children and
52 children with ASD (8-18 years), all matched for age and gender. Furthermore,
EF, IQ, and symptoms of ASD were assessed. Children with NF1 displayed intact
visual form discrimination and intact information integration along the dorsal
visual pathway. Moreover, their reduced performance on a task requiring
integration of information along the ventral visual stream and their more detail
oriented processing style appeared to result from confounding EF impairments and
not from visuoperceptual impairments per se. The co-occurring ASD symptoms and
lower IQ of the children with NF1 did not impact substantially upon their
visuoperceptual performance. These findings point to the large impact of EF
impairments on the performance of visuoperceptual task and suggest that
individuals with NF1 show intact visual form discrimination, intact visual
integration, and typical visual processing style when potential confounding
factors are controlled for. This may have large repercussions for the
interpretation of other findings on visuoperceptual processing in individuals
with NF1. (c) 2017 Wiley Periodicals, Inc.
PMID- 28512746
TI - A panel of microRNAs can be used to determine oral squamous cell carcinoma.
AB - BACKGROUND: Subjective histopathology is currently used to diagnose oral squamous
cell carcinoma (OSCC). We tested if abundances of a panel of microRNA could be an
objective OSCC indicator. METHOD: Literature review enabled identification of 10
microRNAs associated with oral and head and neck malignancies. We extracted RNA
from formalin-fixed paraffin-embedded biopsies; 20 each with OSCC, dysplasia, or
histologically normal epithelium (HNE) and 10 with oral lichen planus (OLP).
Relative abundances of microRNAs in HNE and OSCC were determined using reverse
transcription and then real-time PCR with global mean normalization. MicroRNAs
differentially expressed (test microRNA, T-miR) and non-differentially expressed
(normalization microRNA, N-miR) were identified. The raw microRNA Cq data were
incorporated in a developed algorithm that output a T-miR expression value (T
miREV) score. Raw Cq data from HNE, OSCC, dysplasia, and OLP samples were then
used to test the algorithm scoring and OSCC classification. RESULTS: Four test
and normalization microRNAs were identified. Algorithm output of T-mirEV >1 or <
1 indicated high and low OSCC probability score, respectively, and gave 88.9%
sensitivity, 100% specificity, and 93.5% accuracy. Grouping high and intermediate
T-mirEV scores (T-miREV >=-1) resulted in sensitivity of 90%, specificity of 65%,
and accuracy of 77.5% in OSCC classification. All 20 dysplasias and eight of 10
OLP had T-miREV >=-1 indicating intermediate to high probability of malignant
changes. CONCLUSION: A microRNA panel combined with our algorithm can identify
tissue with probable oncogenic changes. IMPACT: The developed algorithm serves as
a baseline for prospective trials, which may result in potential clinical
utility.
PMID- 28512749
TI - Anxiety genetics: Dispatches from the frontier.
PMID- 28512750
TI - Genetic risk variants for social anxiety.
PMID- 28512748
TI - Genetic influences on ADHD symptom dimensions: Examination of a priori
candidates, gene-based tests, genome-wide variation, and SNP heritability.
AB - Although the heritability of ADHD is estimated to be high, identifying specific
genetic markers remains challenging. Most studies to date have examined the
genetic basis of ADHD by employing dichotomous diagnostic phenotypes, but, as
ADHD symptoms tend to be phenotypically dimensional, an alternative and
potentially informative approach is to examine continuous indices of inattention
and hyperactivity-impulsivity symptoms. The current study aimed to identify
genetic effects on dimensionally-focused adult ADHD-related phenotypes in 990
individuals of European ancestry with intentionally low levels of substance
misuse to avoid confounding. The study used four complementary approaches: (1)
analysis of a priori candidate loci identified in prior meta-analytic work; (2)
gene-based analysis; (3) hypothesis-free genome-wide association testing; and (4)
single nucleotide polymorphism (SNP) heritability via genomic-relatedness-matrix
restricted maximum likelihood analysis (GREML). The GREML analysis included a
bivariate model to test whether the ADHD symptom dimensions index the same
genetic liability. The results revealed significant differential associations
between two a priori loci and ADHD phenotypes, rs6296 in HTR1B with inattention
and rs3746544 in SNAP-25 with hyperactivity-impulsivity. No significant gene
based or genome-wide associations were detected, but SNP heritability revealed
that a large portion of genetic variance was accounted for by common SNPs (44%,
55%, and 59% for inattention, hyperactivity-impulsivity, and total ADHD,
respectively) and substantial shared genetic variance across inattention and
hyperactivity-impulsivity (86%). These findings reveal both unique and common
patterns of genetic influences across dimensional ADHD-related phenotypes. More
broadly, these findings reveal the value in using multiple methods to understand
the genetic etiology of ADHD.
PMID- 28512751
TI - Giant torturous left circumflex artery draining to the right atrium.
AB - Coronary artery anomalies represent a diverse group of congenital disorders
characterized by abnormalities of coronary arteries anatomy. We describe an
extremely rare case of giant torturous left circumflex artery draining to the
right atrium manifesting by palpitations and atrial fibrillation.
PMID- 28512752
TI - An Optimized Two-Photon Fluorescent Probe for Biological Sensing and Imaging of
Catechol-O-Methyltransferase.
AB - A practical two-photon fluorescent probe was developed for highly sensitive and
selective sensing of the activities of catechol-O-methyltransferase (COMT) in
complex biological samples. To this end, a series of 3-substituted 7,8
dihydroxycoumarins were designed and synthesized. Among them, 3-BTD displayed the
best combination of selectivity, sensitivity, reactivity, and fluorescence
response following COMT-catalyzed 8-O-methylation. The newly developed two-photon
fluorescent probe 3-BTD can be used for determining the activities of COMT in
complex biological samples and bio-imaging of endogenous COMT in living cells and
tissue slices with good cell permeability, low cytotoxicity, and high imaging
resolution. All these findings suggest that 3-BTD holds great promise for
developing therapeutic molecules that target COMT, as well as for exploring COMT
associated biological processes and its biological functions in living systems.
Furthermore, the strategy also sheds new light on the development of fluorescent
probes for other conjugative enzymes.
PMID- 28512754
TI - An unusual case of methicillin-resistant Staphylococcus aureus necrotic soft
tissue infection of the lip.
PMID- 28512755
TI - Evaluation of safety of concomitant splenectomy in living donor liver
transplantation: a retrospective study.
AB - In Asian countries, concomitant splenectomy in living donor liver transplantation
(LDLT) is indicated to modulate the portal vein pressure in the small-sized graft
to protect against small for size syndrome. While concomitant splenectomy in
deceased donor liver transplantation is almost contraindicated based on Western
Reports of increased mortality and morbidity rate due to septic complications,
there are few studies about that in LDLT. So, we retrospectively investigated the
clinical outcome of adult LDLT at Kyoto University Hospital from July 2010 to
July 2016. We divided the patients (n = 164) into those with concomitant
splenectomy (n = 88) and those without (n = 76). The splenectomy group showed
significantly increased operative time and intraoperative blood loss (P = 0.008,
P = 0.0007, respectively), and significantly higher rate of postoperative splenic
vein thrombosis and cytomegalovirus infection (P = 0.03, P = 0.016,
respectively). However, there were no significant differences between the two
groups regarding the incidence of postoperative hemorrhage (P = 0.06), post
transplant bacteremia (P = 0.38), infection-related mortality rates (P = 0.8),
acute rejection (P = 0.87), and patient and graft survival (P = 0.66, P = 0.67
respectively); finally, model for end-stage liver disease score above 30 was an
independent predictor for infection-related mortality post-transplant (HR = 5.99,
95% CI = 2.15-16.67, P = 0.001). In conclusion, concomitant splenectomy in LDLT
can be safely performed when indicated.
PMID- 28512753
TI - Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis.
AB - OBJECTIVE: Neurofilament light chains (NfL) are unique to neuronal cells, are
shed to the cerebrospinal fluid (CSF), and are detectable at low concentrations
in peripheral blood. Various diseases causing neuronal damage have resulted in
elevated CSF concentrations. We explored the value of an ultrasensitive single
molecule array (Simoa) serum NfL (sNfL) assay in multiple sclerosis (MS).
METHODS: sNfL levels were measured in healthy controls (HC, n = 254) and two
independent MS cohorts: (1) cross-sectional with paired serum and CSF samples (n
= 142), and (2) longitudinal with repeated serum sampling (n = 246, median follow
up = 3.1 years, interquartile range [IQR] = 2.0-4.0). We assessed their relation
to concurrent clinical, imaging, and treatment parameters and to future clinical
outcomes. RESULTS: sNfL levels were higher in both MS cohorts than in HC (p <
0.001). We found a strong association between CSF NfL and sNfL (beta = 0.589, p <
0.001). Patients with either brain or spinal (43.4pg/ml, IQR = 25.2-65.3) or both
brain and spinal gadolinium-enhancing lesions (62.5pg/ml, IQR = 42.7-71.4) had
higher sNfL than those without (29.6pg/ml, IQR = 20.9-41.8; beta = 1.461, p =
0.005 and beta = 1.902, p = 0.002, respectively). sNfL was independently
associated with Expanded Disability Status Scale (EDSS) assessments (beta =
1.105, p < 0.001) and presence of relapses (beta = 1.430, p < 0.001). sNfL levels
were lower under disease-modifying treatment (beta = 0.818, p = 0.003). Patients
with sNfL levels above the 80th, 90th, 95th, 97.5th, and 99th HC-based
percentiles had higher risk of relapses (97.5th percentile: incidence rate ratio
= 1.94, 95% confidence interval [CI] = 1.21-3.10, p = 0.006) and EDSS worsening
(97.5th percentile: OR = 2.41, 95% CI = 1.07-5.42, p = 0.034). INTERPRETATION:
These results support the value of sNfL as a sensitive and clinically meaningful
blood biomarker to monitor tissue damage and the effects of therapies in MS. Ann
Neurol 2017;81:857-870.
PMID- 28512756
TI - Nitramino- and Dinitromethyl-Substituted 1,2,4-Triazole Derivatives as High
Performance Energetic Materials.
AB - Since highly nitrated nitrogen-rich heterocycles are important motifs in high
energy density materials, extensive studies for the development of such novel
molecules have been underway. A highly energetic moiety, 3-dinitromethyl-5
nitramino-1,2,4-triazole, which consists of a triazole ring, and nitramino and
dinitromethyl groups, has been designed and synthesized. By pairing with nitrogen
rich cations, several ionic derivatives were obtained. Theoretical and
experimental studies show that the hydroxylammonium salt (7) is highly dense, and
has excellent detonation performance with acceptable thermal stablity and
sensitivities, which are superior to those of RDX.
PMID- 28512757
TI - Sense of coherence and oral health in older adults in Southern Brazil.
AB - OBJECTIVE: The aim of this study was to evaluate the association between sense of
coherence and oral health among older adults treated at family health units in
southern Brazil. MATERIAL AND METHODS: The sample was composed of 164 individuals
aged 60 years old or older. Socio-demographic and oral health variables were
collected using a standardised questionnaire. Sense of coherence (SOC) was
measured with the questionnaire proposed by Antonovsky containing 29 closed-ended
questions. Poisson regression analysis was employed to identify factors
associated with SOC. RESULTS: Among the 164 older adults, 53.9% were edentate,
54.5% did not need any type of dental prosthesis, and 82.1% had good/adequate
self-assessed oral health. The multivariate analysis revealed lower SOC scores
among non-white individuals [Mean Ratio (MR)=0.94; 95% CI: 0.91-0.97; P<.001],
with poor/very poor self-assessed oral health (MR=0.85; 95% CI: 0.78-0.91;
P<.001) and with one or more teeth present in the oral cavity (MR=0.94; 95% CI:
0.91-0.97; P<.001). CONCLUSION: The present results show that older adults who
are self-reported as non-white, with one or more teeth in the oral cavity and
with poor/very poor self-assessed oral health have lower SOC scores.
PMID- 28512758
TI - Reporting practices for unsolicited and secondary findings from next-generation
sequencing technologies: Perspectives of laboratory personnel.
AB - While next-generation sequencing (NGS) has enormous potential to identify genetic
causes of disease, the nature of the technology means that it can also identify
additional information about the individual receiving sequencing that is
unrelated to the original rationale for testing. Reporting these unsolicited
findings (UF) to clinicians, and subsequently to patients, could lead to
potentially lifesaving interventions. Most international guidelines provide
limited specific recommendations as to whether these UF should be reported.
Little research has been conducted exploring which of these variants are reported
in practice. Twenty-six interviews were conducted with 27 laboratory personnel,
representing 24 laboratories in Europe (12), Canada (five), and Australasia
(Seven) to explore their reporting practices. There is considerable variation
between laboratories in the reporting of UF. While some limit their reporting to
findings that are relevant to the clinical question, others report UF to varying
degrees. In addition, most laboratory personnel interviewed said that their
laboratories do not actively search for secondary findings in disease-causing
genes unrelated to the clinical question, such as those suggested by the American
College of Medical Genetics and Genomics. Our study highlights that laboratories
are still grappling with decisions about which UF to report from NGS and are
calling for more guidance.
PMID- 28512759
TI - Effect of pH on rheotaxis of bull sperm using microfluidics.
AB - The aim of the present research is to study the effect of pH values on the sperm
rheotaxis properties. Semen collected from bulls was diluted with SOF medium
(1:10). pH of the medium was adjusted using a digital pH meter to the following
pH values: 6.0, 6.2, 6.4, 6.4, 6.8, 7.0. All kinetic parameters of sperm (n =
3,385) were determined through a computer-assisted sperm analysis (CASA) system
using microfluidic devices with controlled flow velocity. The following
parameters were determined: total motility (TM%), positive rheotaxis (PR%),
straightline velocity (VSL, MUm/s), average path velocity (VAP, MUm/s), linearity
(LIN, as VSL/VCL, %), beat cross-frequency (BCF, Hz) and curvilinear velocity
(VCL, MUm/s). Nitric oxide, calcium and potassium were estimated in semen at
different pH values. To confirm the effect of nitric oxide and K+ , we used
sodium nitroprusside (an NO donor) and KCL as (a K+ donor) to see their effect on
sperm PR%. The results showed no difference in TM% at pH (6-7). The PR% was the
lowest at pH 6 and 7. The best parameters for the PR% were at pH 6.4-6.6. The
concentration of Ca+2 did not change at different pH values. The mean NO values
decreased with the increase of pH; however, the mean values of K+ increased with
the increase of pH. Addition of high concentration of NO and K+ to the semen
media at fixed pH level had a negative effect on TM% and PR%. In conclusion, the
bull sperm had the best rheotaxis properties at pH 6.4-6.6 and sensitive to the
change of seminal NO and K+ .
PMID- 28512760
TI - Different perspectives of validity in psychiatry.
AB - It is important to improve our understanding about what might be the specific
characteristics of mental disorders to strengthen the scientific credibility of
psychiatry and to clarify its position among other medical and nonmedical
sciences. On the other hand, this issue has diagnostic, research, therapeutic,
legal, financial, and moral implications. Some authors defend a realistic and
absolutist attitude towards validity and others an instrumental and relativistic
stance. Regarding the organization of concepts, dimensional or categorical
approaches have both advantages and disadvantages. Regarding the methodology by
which validity is sought, it can be oriented externally or internally to the
concept in question. On the other hand, the validity can be expert driven or data
driven, the research can be based on disorders or in symptoms and quantitative or
qualitative methods may be used. In this article, we review all these different
kinds of perspectives that can be taken towards the definition of validity in
psychiatry and the methodology to search for it.
PMID- 28512762
TI - Importance of Group Therapeutic Support for Family Members of Children with
Alopecia Areata: A Cross-Sectional Survey Study.
AB - BACKGROUND/OBJECTIVES: The psychological effect of alopecia areata (AA) is well
documented, but group interaction may help lessen this burden. We aimed to
determine factors that draw patients with AA and their families to group events.
METHODS: Surveys were administered at the annual alopecia areata bowling social
in 2015 and 2016. This event is a unique opportunity for children with AA and
their families to meet others with the disease and connect with local support
group resources from the Minnesota branch of the National Alopecia Areata
Foundation. Data from 2015 and 2016 were combined. Comparisons of subgroups were
performed using Fisher exact tests for response frequencies and percentages and
two-sample t tests for mean values. RESULTS: An equal number of men and women
participated in the study (n = 13 each). The average age was 41.1 years. There
were no significant differences (p > 0.05) in survey responses based on
respondent age or sex. Twenty-three (88.5%) attendees sought to connect with
others with AA and met three or more people during the event. Seventeen (65.4%)
also attended other support group events. Twelve respondents (46.2%) came to
support a friend or family member. One hundred percent of attendees identified
socializing with others with AA as important. CONCLUSIONS: Group interaction is
an important source of therapeutic support for people with AA and their families.
PMID- 28512764
TI - Maternal fructose consumption can affect offspring metabolic outcomes.
PMID- 28512761
TI - Deconstructing white matter connectivity of human amygdala nuclei with thalamus
and cortex subdivisions in vivo.
AB - Structural alterations in long-range amygdala connections are proposed to
crucially underlie several neuropsychiatric disorders. While progress has been
made in elucidating the function of these connections, our understanding of their
structure in humans remains sparse and non-systematic. Harnessing diffusion
weighted imaging and probabilistic tractography in humans, we investigate
connections between two main amygdala nucleus groups, thalamic nuclei, and
cortex. We first parcellated amygdala into deep (basolateral) and superficial
(centrocortical) nucleus groups, and thalamus into six subregions, using
previously established protocols based on connectivity. Cortex was parcellated
based on T1-weighted images. We found substantial amygdala connections to
thalamus, with different patterns for the two amygdala nuclei. Crucially, we
describe direct subcortical connections between amygdala and paraventricular
thalamus. Different from rodents but similar to non-human primates, these are
more pronounced for basolateral than centrocortical amygdala. Substantial white
matter connectivity between amygdala and visual pulvinar is also more pronounced
for basolateral amygdala. Furthermore, we establish detailed connectivity
profiles for basolateral and centrocortical amygdala to cortical regions. These
exhibit cascadic connections with sensory cortices as suggested previously based
on tracer methods in non-human animals. We propose that the quantitative
connectivity profiles provided here may guide future work on normal and
pathological function of human amygdala. Hum Brain Mapp 38:3927-3940, 2017. (c)
2017 Wiley Periodicals, Inc.
PMID- 28512765
TI - Tail gut cyst: an unusual case.
PMID- 28512763
TI - Impact of MLH1 expression on tumor evolution after curative surgical tumor
resection in a murine orthotopic xenograft model for human MSI colon cancer.
AB - Colorectal cancers (CRCs) displaying microsatellite instability (MSI) most often
result from MLH1 deficiency. The aim of this study was to assess the impact of
MLH1 expression per se on tumor evolution after curative surgical resection using
a xenograft tumor model. Transplantable tumors established with the human MLH1
deficient HCT116 cell line and its MLH1-complemented isogenic clone, mlh1-3, were
implanted onto the caecum of NOD/SCID mice. Curative surgical resection was
performed at day 10 in half of the animals. The HCT116-derived tumors were more
voluminous compared to the mlh1-3 ones (P = .001). Lymph node metastases and
peritoneal carcinomatosis occurred significantly more often in the group of mice
grafted with HCT116 (P = .007 and P = .035, respectively). Mlh1-3-grafted mice
did not develop peritoneal carcinomatosis or liver metastasis. After surgical
resection, lymph node metastases only arose in the group of mice implanted with
HCT116 and the rate of cure was significantly lower than in the mlh1-3 group (P =
.047). The murine orthotopic xenograft model based on isogenic human CRC cell
lines allowed us to reveal the impact of MLH1 expression on tumor evolution in
mice who underwent curative surgical resection and in mice whose tumor was left
in situ. Our data indicate that the behavior of MLH1-deficient CRC is not only
governed by mutations arising in genes harboring microsatellite repeated
sequences but also from their defect in MLH1 as such.
PMID- 28512768
TI - Nursing home prices and quality of care - Evidence from administrative data.
AB - There is widespread concern about the quality of care in nursing homes. On the
basis of administrative data of a large health insurance fund, we investigate
whether nursing home prices are associated with relevant quality of care
indicators at the resident level. Our results indicate negative associations
between price and both inappropriate and psychotropic medication. In contrast, we
do not find any relationship between the price and impairments of physical
health.
PMID- 28512766
TI - Mental health outcomes of developmental coordination disorder in late
adolescence.
AB - AIM: To assess the relationship between developmental coordination disorder (DCD)
and mental health outcomes in late adolescence. METHOD: Data were analyzed from
the Avon Longitudinal Study of Parents and Children. Moderate-to-severe DCD was
defined at 7 to 8 years according to the DSM-IV-TR criteria. Mental health was
assessed at 16 to 18 years using self-reported questionnaires: Strengths and
Difficulties Questionnaire, Short Moods and Feelings Questionnaire, and the
Warwick-Edinburgh Mental Well-being Scale. Logistic and linear regressions
assessed the associations between DCD and mental health, using multiple
imputation to account for missing data. Adjustments were made for socio-economic
status, IQ, and social communication difficulties. RESULTS: Adolescents with DCD
(n=168) had an increased risk of mental health difficulties (total Strengths and
Difficulties Questionnaire score) than their peers (n=3750) (odds ratio 1.78, 95%
confidence interval 1.12-2.83, adjusted for socio-economic status and IQ). This
was, in part, mediated through poor social communication skills. Adolescent
females with DCD (n=59) were more prone to mental health difficulties than males.
Greater mental well-being was associated with better self-esteem (beta 0.82,
p<0.001). INTERPRETATION: Individuals with DCD, particularly females, had
increased risk of mental health difficulties in late adolescence. Interventions
that aim to promote resilience in DCD should involve improving social
communication skills and self-esteem.
PMID- 28512767
TI - Duration of major and minor depressive episodes and associated risk indicators in
a psychiatric epidemiological cohort study of the general population.
AB - OBJECTIVE: Hardly any studies exist on the duration of major depressive disorder
(MDD) and factors that explain variations in episode duration that lack biases.
This limits clinical decision-making and leaves patients wondering when they will
recover. METHOD: Data were used from the Netherlands Mental Health Survey and
Incidence Study-2, a psychiatric epidemiological cohort study among a nationally
representative adult population. Respondents with a newly originated depressive
episode were selected: 286 MDD and 107 minor depressive disorder (MinDD) cases.
DSM-IV diagnoses were assessed with the Composite International Diagnostic
Interview 3.0 and episode duration with the Life Chart Interview. RESULTS: Among
MDD cases, median episode duration was 6 months, mean duration was 10.7 months,
and 12% had not recovered at 36 months. Longer duration was associated with
comorbid dysthymia, anxiety disorder, psychotropic medication use (i.e.
antidepressants or benzodiazepines prescribed by a mental health professional),
mental health care use and suicidal behaviour. Better physical and mental
functioning before depression onset predicted shorter duration. Among MinDD
cases, shorter median duration (3 months) but similar mean duration (8.7 months),
risk of chronicity (10% not recovered at 36 months) and risk indicators for
episode duration were found. CONCLUSION: As the risk of chronicity was similar
for MDD and MinDD, MinDD cannot be dismissed as a merely brief mood state.
PMID- 28512769
TI - Modern cardiac surgery: the future of cardiac surgery in Australia.
AB - Cardiac surgery is a relatively young specialty and is undergoing many changes
presently. The advent of catheter-based technology, minimally invasive surgery
and better information regarding the roles of cardiac surgery in the management
of common cardiac disease is changing the way we provide services. In Australia,
attention must be turned to the way cardiac surgical services are provided to
enable delivery of modern procedures. This has implications for the provision of
training. We explore the face of modern cardiac surgery and how this may be taken
up in Australia.
PMID- 28512770
TI - Role of Halide Ions in the Nature of the Magnetic Anisotropy in Tetrahedral CoII
Complexes.
AB - A series of mononuclear tetrahedral CoII complexes with a general molecular
formula [CoL2 X2 ] [L=thiourea and X=Cl (1), Br (2) and I (3)] were synthesized
and their structures were characterized by single-crystal X-ray diffraction.
Direct-current (dc) magnetic susceptibility [chiM T(T) and M(H)] and its slow
relaxation of magnetization were measured for all three complexes. The
experimental dc magnetic data are excellently reproduced by fitting both chiM
T(T) and M(H) simultaneously with the parameters D=+10.8 cm-1 , g1 =2.2, g2 =2.2,
and g3 =2.4 for 1; D=-18.7 cm-1 , giso =2.21 for 2; and D=-19.3 cm-1 , giso =2.3
for 3. The replacement of chloride in 1 by bromide or iodide (in 2 and 3,
respectively) was accompanied by a change in both sign and magnitude of the
magnetic anisotropy D. Field-induced out-of-phase susceptibility signals observed
in 10 % diluted samples of 1-3 imply slow relaxation of magnetization of
molecular origin. To better understand the magnetization relaxation dynamics of
complexes 1-3, detailed ab initio CASSCF/NEVPT2 calculations were performed. The
computed spin Hamiltonian parameters are in good agreement with experimental
data. In particular, the calculations unveil the role of halide ions in switching
the sign of D on moving from Cl- to I- . The large spin-orbit coupling constant
associated with the heavier halide ion and weaker pi donation reduces the ground
state-excited state gap, which leads to a larger contribution to negative D for
complex 3 compared to complex 1. Further magnetostructural D correlations were
developed to understand the role of structural distortion in the sign and
magnitude of D values in this family of complexes.
PMID- 28512771
TI - Negative Cardiovascular Consequences of Small Molecule Immunosuppressants.
AB - Immunosuppressants are critical after transplantation and prescribed as immune
modulators for autoimmune disorders and glomerulonephritides. Immunosuppressants
include large (e.g., thymoglobulin, alemtuzumab, and rituximab) and small
molecules (e.g., corticosteroids, calcineurin inhibitors, antimetabolites, and
mammalian target of rapamycin (mTOR) inhibitors). The majority of the small
molecules worsen traditional cardiovascular risks. This review describes
cardiovascular risks of small molecule immunosuppressants: corticosteroids,
calcineurin inhibitors (tacrolimus and cyclosporine), and mTOR inhibitors
(rapamycin), by categorizing these risks into two categories: ischemic heart
disease and nonischemic cardiac effects.
PMID- 28512772
TI - Subspecialty approach for the management of acute cholecystitis: an alternative
to acute surgical unit model of care.
AB - BACKGROUND: Acute cholecystitis is a common condition. Recent studies have shown
an association between creation of an acute surgical unit (ASU) and improved
outcomes. This study aimed to evaluate the outcomes of a subspecialty based
approach to the management of acute cholecystitis as an alternative to the
traditional 'generalist' general surgery approach or the ASU model. METHOD: A 6
year retrospective analysis of outcomes in patients admitted under a dedicated
upper gastrointestinal service for acute cholecystitis undergoing emergency
laparoscopic cholecystectomy. RESULTS: Seven hundred emergency laparoscopic
cholecystectomies were performed over this time. A total of 486 patients were
available for analysis. The median time to operation was 2 days and median length
of operation was 80 min. A total of 86.9% were performed during daylight hours.
Eight cases were converted to open surgery (1.6%). Intra-operative
cholangiography was performed in 408 patients. The major complication rate was
8.2%, including retained common bile duct stones (2.3%), sepsis (0.2%), post
operative bleeding (0.4%), readmission (0.6%), bile leak (2.1%), AMI (0.4%),
unscheduled return to theatre (0.6%) and pneumonia (0.8%). There were no
mortalities and no common bile duct injuries. CONCLUSION: Over a time period that
encompasses the current publications on the ASU model, a subspecialty model of
care has shown consistent results that exceed established benchmarks.
Subspecialty management of complex elective pathologies has become the norm in
general surgery and this study generates the hypothesis that subspecialty
management of patients with complex emergency pathologies should be considered a
valid alternative to ASU. Access block to emergency theatres delays treatment and
prolongs hospital stay.
PMID- 28512773
TI - Natural history of intraductal papillary mucinous neoplasm and non-neoplastic
cyst: long-term imaging follow-up study.
AB - BACKGROUND: To identify differences in incidence and mortality of pancreatic
cancer (PC) between intraductal papillary mucinous neoplasm (IPMN) and non
neoplastic cyst. METHODS: Patients with pancreatic cyst (n = 526; 263 with IPMN
and 263 with non-neoplastic cyst matched for age, sex, and diagnosis year) were
periodically followed-up with imaging. Hazard ratio (HR), standardized incidence
ratio (SIR), and standardized mortality ratio (SMR) for PC and PC-related
mortality were estimated. RESULTS: During a mean follow-up of 57.5 months with
3,376 computed tomography scans and 1,079 magnetic resonance imaging scans, 5
year cumulative PC incidence was 4.0% for IPMN and 0% for non-neoplastic cyst,
respectively (HR 5.2; P = 0.031). During a mean follow-up of 73.1 months, 5-year
cumulative PC-related mortality was 2.6% for IPMN and 0% for non-neoplastic cyst,
respectively (HR 4.5; P = 0.05). Compared with the general population in Japan,
patients with IPMN, but not those with non-neoplastic cyst, had significantly
increased risks of PC incidence (SIR 22.03) and related mortality (SMR 15.9).
CONCLUSIONS: During long-term imaging follow-up, patients with IPMN developed PC
over time, whereas none of the patients with non-neoplastic cyst developed it
within 5 years. Compared with the general population, patients with IPMN, but not
those with non-neoplastic cyst, were at risk of PC and related mortality.
PMID- 28512774
TI - Cybersecurity and medical devices: A practical guide for cardiac
electrophysiologists.
AB - Medical devices increasingly depend on software. While this expands the ability
of devices to perform key therapeutic and diagnostic functions, reliance on
software inevitably causes exposure to hazards of security vulnerabilities. This
article uses a recent high-profile case example to outline a proactive approach
to security awareness that incorporates a scientific, risk-based analysis of
security concerns that supports ongoing discussions with patients about their
medical devices.
PMID- 28512776
TI - Can telomere length be used as a biomarker for cardiovascular diseases? Insights
from a large clinical study.
PMID- 28512775
TI - A porphyrin-based fluorescence method for zinc determination in commercial
propolis extracts without sample pretreatment.
AB - The quantification of zinc in over-the-counter drugs as commercial propolis
extracts by molecular fluorescence technique using meso-tetrakis(4
carboxyphenyl)porphyrin (H2 TCPP4 ) was developed for the first time. The
calibration curve is linear from 6.60 to 100 nmol L-1 of Zn2+ . The detection and
quantification limits were 6.22 nmol L-1 and 19.0 nmol L-1 , respectively. The
reproducibility and repeatability calculated as the percentage variation of
slopes of seven calibration curves were 6.75% and 4.61%, respectively. Commercial
propolis extract samples from four Brazilian states were analyzed and the results
(0.329-0.797 mg/100 mL) obtained with this method are in good agreement with that
obtained with the Atomic Absorption Spectroscopy (AAS) technique. The method is
simple, fast, of low cost and allows the analysis of the samples without
pretreatment. Moreover the major advantage is that Zn-porphyrin complex presents
fluorescent characteristic promoting the selectivity and sensitivity of the
method.
PMID- 28512777
TI - The Australian laparoscopic radical prostatectomy learning curve.
AB - BACKGROUND: International estimates of the laparoscopic radical prostatectomy
(LRP) learning curve extend to as many as 1000 cases, but is unknown for
Fellowship-trained Australian surgeons. METHODS: Prospectively collected data
from nine Australian surgeons who performed 2943 consecutive LRP cases was
retrospectively reviewed. Their combined initial 100 cases (F100, n = 900) were
compared to their second 100 cases (S100, n = 782) with two of nine surgeons
completing fewer than 200 cases. RESULTS: The mean age (61.1 versus 61.1 years)
and prostate specific antigen (7.4 versus 7.8 ng/mL) were similar between F100
and S100. D'Amico's high-, intermediate- and low-risk cases were 15, 59 and 26%
for the F100 versus 20, 59 and 21% for the S100, respectively. Blood transfusions
(2.4 versus 0.8%), mean blood loss (413 versus 378 mL), mean operating time (193
versus 163 min) and length of stay (2.7 versus 2.4 days) were all lower in the
S100. Histopathology was organ confined (pT2) in 76% of F100 and 71% of S100.
Positive surgical margin (PSM) rate was 18.4% in F100 versus 17.5% in the S100 (P
= 0.62). F100 and S100 PSM rates by pathological stage were similar with pT2 PSM
12.2 versus 9.5% (P = 0.13), pT3a PSM 34.8 versus 40.5% (P = 0.29) and pT3b PSM
52.9 versus 36.4% (P = 0.14). CONCLUSION: There was no significant improvement in
PSM rate between F100 and S100 cases. Perioperative outcomes were acceptable in
F100 and further improved with experience in S100. Mentoring can minimize the LRP
learning curve, and it remains a valid minimally invasive surgical treatment for
prostate cancer in Australia even in early practice.
PMID- 28512778
TI - CAGI4 Crohn's exome challenge: Marker SNP versus exome variant models for
assigning risk of Crohn disease.
AB - Understanding the basis of complex trait disease is a fundamental problem in
human genetics. The CAGI Crohn's Exome challenges are providing insight into the
adequacy of current disease models by requiring participants to identify which of
a set of individuals has been diagnosed with the disease, given exome data. For
the CAGI4 round, we developed a method that used the genotypes from exome
sequencing data only to impute the status of genome wide association studies
marker SNPs. We then used the imputed genotypes as input to several machine
learning methods that had been trained to predict disease status from marker SNP
information. We achieved the best performance using Naive Bayes and with a
consensus machine learning method, obtaining an area under the curve of 0.72,
larger than other methods used in CAGI4. We also developed a model that
incorporated the contribution from rare missense variants in the exome data, but
this performed less well. Future progress is expected to come from the use of
whole genome data rather than exomes.
PMID- 28512780
TI - Novel enantioselective fluorescent sensors for tartrate anion based on
acridinezswsxa.
AB - Novel chiral fluorescence sensors L-1 and D-1 incorporating N-Boc-protected
alanine and acridine moieties were synthesized. The recognition ability of the
sensors was studied by fluorescence titration, 1 H NMR spectroscopy and density
functional theory (DFT) calculations. The sensors exhibited good enantioselective
fluorescent sensing ability toward enantiomers of tartrate anion for the selected
carboxylate anions and formed 1: 1 complexes by multiple hydrogen bonding
interactions.
PMID- 28512782
TI - Aortocoronary artery dissection: a partial aortic root remodelling, aortic valve
repair and coronary artery bypass.
PMID- 28512779
TI - Structure of protein emulsion in food impacts intestinal microbiota, caecal
luminal content composition and distal intestine characteristics in rats.
AB - SCOPE: Few studies have evaluated in vivo the impact of food structure on
digestion, absorption of nutrients and on microbiota composition and metabolism.
In this study we evaluated in rat the impact of two structures of protein
emulsion in food on gut microbiota, luminal content composition, and intestinal
characteristics. METHODS AND RESULTS: Rats received for 3 weeks two diets of
identical composition but based on lipid-protein matrices of liquid fine (LFE) or
gelled coarse (GCE) emulsion. LFE diet led to higher abundance, when compared to
the GCE, of Lactobacillaceae (Lactobacillus reuteri) in the ileum, higher beta
diversity of the caecum mucus-associated bacteria. In contrast, the LFE diet led
to a decrease in Akkermansia municiphila in the caecum. This coincided with
heavier caecum content and higher amount of isovalerate in the LFE group. LFE
diet induced an increased expression of (i) amino acid transporters in the ileum
(ii) glucagon in the caecum, together with an elevated level of GLP-1 in portal
plasma. However, these intestinal effects were not associated with modification
of food intake or body weight gain. CONCLUSION: Overall, the structure of protein
emulsion in food affects the expression of amino acid transporters and gut
peptides concomitantly with modification of the gut microbiota composition and
activity. Our data suggest that these effects of the emulsion structure are the
result of a modification of protein digestion properties.
PMID- 28512781
TI - Developmental regulation and localization of carnitine palmitoyltransferases
(CPTs) in rat brain.
AB - While the brain's high energy demands are largely met by glucose, brain is also
equipped with the ability to oxidize fatty acids for energy and metabolism. The
brain expresses the carnitine palmitoyltransferases (CPTs) that mediate carnitine
dependent entry of long-chain acyl-CoAs into the mitochondrial matrix for beta
oxidation - CPT1a and CPT2 located on the outer and inner mitochondrial
membranes, respectively. Their developmental profile, regional distribution and
activity as well as cell type expression remain unknown. We determined that brain
CPT1a RNA and total protein expression were unchanged throughout post-natal
development (PND0, PND7, PND14, PND21 and PND50); however, CPT2 RNA peaked at PND
21 and remained unchanged through PND50 in all regions studied (cortex,
hippocampus, midbrain, and cerebellum). Both long-chain acyl CoA dehydrogenase
and medium acyl-CoA dehydrogenase showed a similar developmental profile to CPT2.
Acylcarnitines, generated as a result of CPT1a activity, significantly increased
with age and peaked at PND21 in all brain regions, concurrent with the increased
expression of enzymes involved in mitochondrial beta-oxidation. The CPT system is
highly enriched in vivo in hippocampus and cerebellum, relative to cortex and
midbrain, and is exclusively present in astrocytes and neural progenitor cells,
while absent in neurons, microglia, and oligodendrocytes. Using radiolabeled
oleate, we demonstrate regional differences in brain fatty acid oxidation that
may be blocked by the irreversible CPT1a inhibitor etomoxir. This study
contributes to the field of knowledge in brain cell-specific metabolic pathways,
which are important for understanding normal brain development and aging, as well
as pathophysiology of neurological diseases. Read the Editorial Comment for this
article on page 347.
PMID- 28512783
TI - Effect of silver-loaded PMMA on Streptococcus mutans in a drip flow reactor.
AB - Orthodontic retention has been proposed as a life-long commitment for patients
who desire to maintain straight teeth. However, the presence of foreign material
increases risk of bacterial colonization and caries formation, of which
Streptococcus mutans is a key contributor. Multiple studies have assessed the
ability of silver to be added to base plate material and resist attachment of S.
mutans. However, it does not appear that long-term washout in connection with
biofilm growth under physiologically relevant conditions has been taken into
consideration. In this study, silver was added to base plate material and exposed
to short- or long-term washout periods. Materials were then assessed for their
ability to resist biofilm formation of S. mutans using a drip flow reactor that
modeled the human oral environment. Data indicated that silver was able to resist
biofilm formation following short-term washout, but long-term washout periods
resulted in a lack of ability to resist biofilm formation. These data will be
important for future development of base plate materials to achieve long-term
antimicrobial efficacy to reduce risk of caries formation and benefit patients in
the long term. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A:
2632-2639, 2017.
PMID- 28512784
TI - Evaluation of aromatic radiobromination by nucleophilic substitution using
diaryliodonium salt precursors.
AB - Radiobromine-labeled compounds can be used for positron emission tomography (PET)
imaging (ie, 76 Br) and for radiation therapy (ie, 77 Br). However, the commonly
used electrophilic substitution reaction using no-carrier-added radiobromide does
not always afford the desired product due to the high reactivity of the
brominating intermediate. A nucleophilic substitution by bromide, such as
radiobromination of iodonium precursors, provides an alternative route for the
synthesis of bromo-radiopharmaceuticals. The applicability of aromatic
radiobromination by nucleophilic substitution using diaryliodonium salt
precursors was evaluated using iodonium model compounds and [76 Br]/[77
Br]bromide. Radiobromination was observed under all conditions tested, in up to
quantitative yields. A QMA cartridge treatment method and a base-free method have
been developed, and no extra base is needed for either methods. The base-free
conditions are mild and afford much cleaner reactions. Up to 20% water is
tolerated in the reactions without reducing the radiochemical yields. No-carrier
added and carrier-added reactions afforded similar results. 4-Bromobenzaldehyde
and 4-bromobenzoate have been radiosynthesized reliably and in good yields. These
results indicate that this method is robust and efficient and thus will provide a
route for radiobromination of electron-deficient arenes and an alternative route
for the synthesis of bromo-radiopharmaceuticals for biological evaluations.
PMID- 28512785
TI - Clinical, immunologic, molecular analyses and outcomes of iranian patients with
LRBA deficiency: A longitudinal study.
AB - BACKGROUND: LPS-responsive beige-like anchor protein (LRBA) deficiency is a
combined immunodeficiency caused by mutation in LRBA gene. The patients have a
variety of clinical symptoms including hypogammaglobulinemia, recurrent
infections, autoimmunity, and enteropathy. METHODS: A total of 17 LRBA-deficient
patients were enrolled in this longitudinal study. For all patients, demographic
information, clinical records, laboratory, and molecular data were collected.
RESULT: Hypogammaglobulinemia was reported in 14 (82.4%), CD4+ T-cell deficiency
in five (29.4%), NK cell deficiency in three (21.4%), and CD19+ B-cell deficiency
in 11 (64.7%) patients. All patients had history of infectious complications;
pneumonia was the most common (76.5%) occurring infection. A history of
lymphoproliferative disorders was observed in 14 (82.3%), enteropathy in 13
(76.5%), allergic symptoms in six (35.5%), neurologic problems in four (23.5),
and autoimmunity (mostly autoimmune cytopenia) in 13 (76.5%) patients. Sirolimus
treatment improved enteropathy of patients with remarkable success. The 20-year
overall survival rate declined to 70.6%. CONCLUSION: LRBA deficiency has a very
broad and variable phenotype and should be considered, especially in children
with early-onset hypogammaglobulinemia, severe autoimmune manifestations,
enteropathy, lymphoproliferation, and recurrent respiratory tract infections.
PMID- 28512786
TI - A Single-Molecular AND Gate Operated with Two Orthogonal Switching Mechanisms.
AB - Single-molecular electronics is a potential solution to nanoscale electronic
devices. While simple functional single-molecule devices such as diodes,
switches, and wires are well studied, complex single-molecular systems with
multiple functional units are rarely investigated. Here, a single-molecule AND
logic gate is constructed from a proton-switchable edge-on gated
pyridinoparacyclophane unit with a light-switchable diarylethene unit. The AND
gate can be controlled orthogonally by light and protonation and produce desired
electrical output at room temperature. The AND gate shows high conductivity when
treated with UV light and in the neutral state, and low conductivity when treated
either with visible light or acid. A conductance difference of 7.3 is observed
for the switching from the highest conducting state to second-highest conducting
state and a conductance ratio of 94 is observed between the most and least
conducting states. The orthogonality of the two stimuli is further demonstrated
by UV-vis, NMR, and density function theory calculations. This is a demonstration
of concept of constructing a complex single-molecule electronic device from two
coupled functional units.
PMID- 28512787
TI - Corrigendum.
PMID- 28512788
TI - Outcomes of patients with relapsed/refractory Hodgkin lymphoma progressing after
autologous stem cell transplant in the current era of novel therapeutics: A
retrospective analysis.
AB - Patients with relapsed/refractory Hodgkin lymphoma (RR-HL) who progress or
relapse following autologous stem cell transplantation (ASCT) have historically
had a poor prognosis. Several novel agents, particularly brentuximab vedotin,
have shown efficacy in this setting. However, there remains a paucity of data
characterizing outcomes outside of clinical trials and how these novel agents
have impacted prognosis in general population of patients with RR-HL. Here, we
conducted a retrospective analysis to evaluate outcomes in 87 patients with RR-HL
with relapse post-ASCT. Treatment with novel agents (including brentuximab
vedotin) was associated with significant improvement in median overall survival
(OS) compared to patients who did not receive novel agents (85.6 vs 17.1 months;
P < .001). Additional factors associated with improved OS in univariate analysis
include treatment with radiation therapy post-ASCT (34.1 vs 17.0 months; P =
.015), chemosensitivity (i.e., relapsed compared to primary refractory disease;
51.8 vs 25.6 months; p = 0.013), initial response to ASCT (i.e., CR/PR compared
to SD/PD; 46.1 vs 20.4 months; P = .011), and transplantation in 2010 and later
compared to prior to 2010 (not reached vs 24.5 months; P = .025). The current
study demonstrates markedly improved OS in RR-HL patients treated with novel
therapeutics and lends "real world" credence to the role of these agents in
improving outcomes in the current era.
PMID- 28512790
TI - Ultrastructural changes of the glomerular basement membrane... unmasked by C4d
staining.
PMID- 28512792
TI - Expression of aquaporin 4 in the chicken ovary in relation to follicle
development.
AB - In the mammalian ovary, aquaporins (AQPs) are thought to be involved in the
regulation of fluid transport within the follicular wall and antrum formation.
Data concerning the AQPs in the avian ovary is very limited. Therefore, the
present study was designed to examine whether the AQP4 is present in the chicken
ovary, and if so, what is its distribution in the ovarian compartment of the
laying hen. Localization of AQP4 in the ovarian follicles at different stage of
development was also investigated. After decapitation of hens the stroma with
primordial follicles and white (1-4 mm), yellowish (4-8 mm), small yellow and the
three largest yellow pre-ovulatory follicles F3-F1 (F3 < F2 < F1; 20-36 mm) were
isolated from the ovary. The granulosa and theca layers were separated from the
pre-ovulatory follicles. The AQP4 mRNA and protein were detected in all examined
ovarian compartments by the real-time PCR and Western blot analyses,
respectively. The relative expression of AQP4 was depended on follicular size and
the layer of follicular wall. It was the lowest in the granulosa layer of pre
ovulatory follicles and the highest in the ovarian stroma as well as white and
yellowish follicles. Along with approaching of the largest follicle to ovulation
the gradual decrease in AQP4 protein level in the granulosa layer was observed.
Immunoreactivity for AQP4 was present in the granulosa and theca cells (theca
interna >= theca externa > granulosa). The obtained results suggest that AQP4 may
take part in the regulation of water transport required for follicle development
in the chicken ovary.
PMID- 28512793
TI - 5-Azacytidine-mediated hMSC behavior on electrospun scaffolds for skeletal muscle
regeneration.
AB - Incomplete regeneration after trauma or muscular dysfunction is a common problem
in muscle replacement therapies. Recent approaches in tissue engineering allow
for the replication of skeletal muscle structure and function in vitro and in
vivo by molecular therapies and implantable scaffolds which properly address
muscle cells toward myotube differentiation and maturation. Here, we investigate
the in vitro response of human mesenchymal stem cells (hMSC) on electrospun
fibers made of polycaprolactone (PCL) in the presence of 5-azacytidine (5-AZA) to
evaluate how fibrous network may influence the therapeutic effect of drug during
in vitro myogenesis. Biological studies demonstrate the ability of hMSCs to
differentiate in mature myofibers in supplemented (myogenic) and, preferentially,
in 5-AZA-enriched culture. PCL electrospun fibers amplify the 5-AZA capability to
induce a low proliferation rate in hMSC, thus promoting hMSC differentiation (MTT
assay). Qualitative (Azan Mallory stain, immunofluorescence assay, SEM analyses)
and quantitative (ELISA test) assays confirm the synergistic contribution of PCL
electrospun fibers and 5-AZA on in vitro myotubes formation and maturation. This
result is also confirmed by the expression of muscle-specific proteins related to
the myogenic mechanisms in the presence of other muscle inductive signals (i.e.,
oxytocin, Tweak). Hence, we suggest the use of PCL electrospun fibers as
interesting preclinical model to explore the effect of drugs and
chemotherapeutics administration after damaged muscle resection. (c) 2017 Wiley
Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2551-2561, 2017.
PMID- 28512794
TI - Free and total plasma concentrations of elvitegravir/cobicistat during pregnancy
and postpartum: a case report.
PMID- 28512796
TI - Poster - Thurs Eve-11: Quantitative imaging of 213Bi alpha-emitter with a beta
imager.
AB - Targeted alpha-particle emitter therapy is emerging as a promising approach for
treating metastatic cancer. An understanding of the biodistribution of targeted
alpha-emitters at the cell level is important in evaluating potential efficacy
and toxicity. This is best accomplished by autoradiography of tissue samples, ex
vivo. We have investigated the feasibility of using a high resolution,
quantitative beta-imager (Biospace Mesures beta-Imager) to detect the short-lived
alpha-particle emitter, Bismuth-213 (213Bi). The advantages of this detector
include: shorter acquisition time than film-based autoradiography, which is
critical for an isotope with such a short half-life; high resolution; and data
acquisition in list mode. While our interest in 213Bi lies in the alpha, the
decay chain includes high energy beta- particles, enabling this study. Published
studies using the beta-Imager show predominantly qualitative results, with the
quantitative depending on long exposure time or direct comparisons. At low count
rate the detector auto-regulates by varying the HV, directly affecting the
results. We imaged a phantom prepared from 213Bi in 5% gelatin. We plot only the
results in a narrow HV range and fit an exponential decay function to obtain a
half-life close to the expected value. We plot the ratio of the exponential fit
to the measured count rate value against HV for all count rates and find a
functional correlation between HV and count rate. A similar correction for gas
flow ratio variations is also applied. As the remaining fluctuations conform to
Gaussian statistics, this suggests that we have successfully calibrated 213Bi for
future studies.
PMID- 28512791
TI - Peptide-Functionalized Fluorescent Particles for In Situ Detection of Nitric
Oxide via Peroxynitrite-Mediated Nitration.
AB - Nitric oxide (NO) is a free radical signaling molecule that plays a crucial role
in modulating physiological homeostasis across multiple biological systems. NO
dysregulation is linked to the pathogenesis of multiple diseases; therefore, its
quantification is important for understanding pathophysiological processes. The
detection of NO is challenging, typically limited by its reactive nature and
short half-life. Additionally, the presence of interfering analytes and
accessibility to biological fluids in the native tissues make the measurement
technically challenging and often unreliable. Here, a bio-inspired peptide-based
NO sensor is developed, which detects NO-derived oxidants, predominately
peroxynitrite-mediated nitration of tyrosine residues. It is demonstrated that
these peptide-based NO sensors can detect peroxynitrite-mediated nitration in
response to physiological shear stress by endothelial cells in vitro. Using the
peptide-conjugated fluorescent particle immunoassay, peroxynitrite-mediated
nitration activity with a detection limit of ~100 * 10-9 m is detected. This
study envisions that the NO detection platform can be applied to a multitude of
applications including monitoring of NO activity in healthy and diseased tissues,
localized detection of NO production of specific cells, and cell
based/therapeutic screening of peroxynitrite levels to monitor pronitroxidative
stress in biological samples.
PMID- 28512795
TI - Influence of primary site on metastatic distribution and survival in stage IV
colorectal cancer.
AB - BACKGROUND: To assess pattern distribution and prognosis of the three anatomical
entities of metastatic colorectal cancer, and influence of treatment of
metastases on survival. METHODS: Patients presenting with stage IV colorectal
cancer (synchronous group), or who developed metastatic recurrence (metachronous
group) after initial curative treatment between January 2005 and August 2015 were
reviewed. Right sided (cecum to transverse colon), left sided (splenic flexure to
sigmoid colon) and rectal cancers were identified. Distribution of metastases
were noted as hepatic, lung or peritoneal. RESULTS: Of 374 patients, 276 were
synchronous, 98 were metachronous. Metachronous group had a better 3-year
survival (54%, 95% CI: 42-64 versus 33%, 95% CI: 27-39, log rank P = 0.0038).
There were equal numbers of right (n = 119), left (n = 115) and rectal cancers (n
= 140). Rectal cancers had a higher metastatic recurrence, yet demonstrated
better 3-year survival (right colon 45%, 95% CI: 19-67, left colon 49%, 95% CI:
27-68, rectum 59%, 95% CI: 42-72, P = 0.39) due to higher proportions of
metachronous patients undergoing treatment for metastases (40 versus 14%). Over
half of all organ metastases spread to liver, with equal distribution from all
three anatomical groups. Rectal cancers showed highest preponderance for lung
metastases. CONCLUSION: Rectal cancers have a higher chance of recurring, with a
higher metastatic rate to the lung, yet demonstrate better survival outcomes in
metastatic colorectal cancer, reflecting the benefit of intervention for
metastases.
PMID- 28512797
TI - Poster - Thurs Eve-22: Image guided radiation therapy for lung cancer.
AB - OBJECTIVE: To determine the geometric accuracy of conventional and stereotactic
lung radiotherapy using cone-beam CT image guidance, and assess the efficacy of
these image-guided radiation therapy (IGRT) processes. MATERIALS AND METHODS:
IGRT was first used for our stereotactic lung program, where high geometric
accuracy is required to deliver high doses in few fractions. The initial
positional accuracy for 47 patients was assessed by registering daily CBCT to the
planning CT; the patient position was corrected when the CBCT indicated
discrepancies > +/- 3 mm in any direction. For 19 of these patients, a second
CBCT was acquired to assess the residual error. IGRT was also used to assess the
initial and residual errors for lung cancer patients treated conventionally with
(14 pts; 584 CBCT) and without (25 pts; 1032 CBCT) a remote-controlled treatment
couch. Systematic (Sigma) and random (sigma) positional errors were assessed for
these three groups. RESULTS: For stereotactic lung patients, Sigma and sigma
ranged between 4.1 and 6.1 mm. IGRT reduces these errors to 1.2-1.9 mm, raising
the proportion of patients within +/- 3 mm from 16% to 82%. For conventional lung
cancer patients, Sigma and sigma ranged between 1.4 and 3.8 mm, and IGRT raises
the proportion of patients within +/- 3 mm from 27% to 67%, with the remote
controlled couch further improving this proportion to 84%. CONCLUSION: IGRT
clearly confirms the high geometric accuracy required for stereotactic lung
patients. This new paradigm has been transported to patients with locally
advanced lung cancer, with similar accuracy.
PMID- 28512798
TI - Sci-Thurs PM: Delivery-05: One year of learning from incidents.
AB - The aim of this study is to quantify the effect of an incident learning system in
radiation therapy. The system is designed to detect all occurrences of "an
unwanted or unexpected change from a normal system behaviour that causes or has
the potential to cause an adverse effect to persons or equipment". Our
application to radiation therapy defines 5 incident types, four levels of
severity and four work domains where errors discovered during routine quality
assurance within each domain were not classified as incidents. During 2007, we
recorded, corrected, investigated, determined root cause and learned from 657
incidents. The vast majority of these incidents were classified as potential
minor clinical incidents having little or no impact on patient treatment. The
value of the system lies in the application of the learning portion of the
investigation. We demonstrated a dramatic reduction in the rate of more severe
incidents by the implementation of several simple tools. Our results also show a
reduction of incidents on accelerators treating essentially a single disease
site. The only treatment unit treating with both image guidance and intensity
modulation recorded the fewest incidents while the cobalt unit with the least
technological assistance recorded three times the average treatment unit
incidents with a higher severity. Additionally, although the rate of incidents at
the point of treatment delivery was low, the impact of those incidents was
substantially higher than that of incidents originating during treatment
planning. This system has proven to be a powerful program management tool.
PMID- 28512799
TI - Poster - Thurs Eve-33: Initial implementation of a novel, measurement-based IMRT
QA method.
AB - Current measurement-based QA for IMRT typically involves a composite dose
delivery to a phantom. However, this approach does not allow a direct dosimetric
evaluation of the delivered treatment with respect to the patient anatomy. In
this work we implement a novel, measurement-based IMRT QA method which provides
an accurate reconstruction of the 3D-dose distribution in the patient model. The
RPC Head&Neck phantom and two clinical prostate cases have been examined to date.
Step & shoot plans were developed satisfying required dose metrics. A 2D-array of
dose chambers (MatriXX, IBA Dosimetry) was mounted on a linear accelerator to
capture delivered fluence. The measurement data were read directly by the control
software (COMPASS, IBA Dosimetry), which also provides the ability to import
patient plan data from the TPS. The COMPASS software also includes a dose
calculation engine and head fluence model and requires beam commissioning
procedures analogous to those of a TPS. Reconstructed doses and DVHs were
compared to those calculated by the TPS. The beam model in the COMPASS software
was able to predict percentage depth dose and X and Y profiles for MLC-defined
apertures ranging from 1*1-20*20 cm?2 to within 1.5% (depth-dose), 2.0% (in-field
profiles), and 2.5% (out-of-field profiles). Reconstructed doses in the test
plans were mostly within 2% of those in the TPS. DVHs compared to <1.2%.
Reconstructed doses were overlaid on CT data and contoured structures, to enable
a clinically useful understanding of discrepancies as compared to the TPS plan.
Research partially sponsored by IBA Dosimetry.
PMID- 28512800
TI - Poster - Thurs Eve-04: Mathematical modeling of liver metastases tumour growth
and control with radiotherapy.
AB - Generating an optimized radiation treatment plan requires understanding the
factors affecting tumour control. Mathematical models of tumour dynamics may help
in future studies of factors predicting tumor sensitivity to radiotherapy. In
this study, a time-dependent differential model, incorporating biological cancer
markers, is presented to describe pre-treatment tumour growth, response to
radiation, and recurrence. The model uses Gompertzian growth to model pre
treatment tumour growth. The effect of radiotherapy is handled by a realistic
cell-kill term that includes a volume-dependent change in tumour sensitivity.
Post-treatment, a Gompertzian, accelerated, delayed repopulation is employed. As
proof-of-concept, we examined the fit of the model's prediction using various
liver enzyme levels as markers of metastatic liver tumour growth in a liver
cancer patient. Enzyme data were derived from repeated serum blood tests, and
radiation treatment-related data were retrieved from the patient's chart. A
tumour clonogen population model was formulated. Each enzyme was coupled to the
same tumour population, and served as surrogates of the tumour. This dynamical
model was solved numerically and compared to the measured enzyme levels. By
minimizing the mean-squared error of the model enzyme predictions, we determined
the following tumour model parameters: growth rate prior to treatment was 0.7%
per day; the fractional radiation cell kill for the prescribed dose was 60% per
day; and tumour repopulation rate was 3.5% per day. These preliminary results
provided the basis to test the model in a larger series of patients, to apply
biological markers for improving the efficacy of radiotherapy by determining the
underlying tumour dynamics.
PMID- 28512801
TI - Poster - Thurs Eve-15: Comparison of Cobalt-60 and 6 MV linac based tomotherapy:
A prostate case study.
AB - Previous work reported by us has shown the potential for Cobalt-60 (Co-60)
tomotherapy for sites with small separations such as in head and neck site. In
this work we extend our investigations by comparing tomotherapy plans for the
treatment of a typical prostate cancer obtained for 6 MV and Co-60 beams. Beam
collimation was provided by the MIMiC(r) (NOMOS Corporation, Sewickly, PA) multi
leaf collimator (MLC). Both plans used 21 beam angles, each utilizing the central
10 leaf-pairs of the MLC for intensity modulation. An in-house inverse treatment
planning program, based on the active-set conjugate gradient method, was used for
dose-volume optimization. BEAMnrc and DOSXYZnrc Monte Carlo simulated beam and
dose data, including inhomogeneity corrections, were used to calculate the
optimized tomotherapy dose distributions. Prostate, rectum, and external body
contours were outlined and dose-volume optimization objectives were set to
deliver a minimum of 95% and a maximum of 105% of the 76 Gy dose prescription to
the prostate and limiting only 20% of the rectum volume to receive ? 70 Gy. A
quantitative analysis of the dose distributions and dose-area histograms show
that both Co-60 and 6 MV plans achieve the initial objectives for target
(prostate) and organ at risk (rectum). Although the dose to the body and rectum
for Co-60 is slightly higher than that for 6 MV, it satisfies the plan objectives
based on the clinical dose tolerance. Our results demonstrate that Co-60 based
tomotherapy can provide clinically competitive dose distributions for the
treatment of prostate cancer.
PMID- 28512802
TI - Poster - Thurs Eve-26: Influence of MLC leaf edge and tongue and groove effect on
IMRT dose distributions.
AB - An important consideration when using multileaf collimators (MLCs) for IMRT
delivery is the correct account of leaf edge effects. To study these effects, two
maps were constructed from a clinical beam's step and shoot delivery sequence: a
time-weighted leaf edge position (LEP) map where the pixel intensity was
proportional to the length of time that a leaf edge defined the edge of any
segment within the field, and a (TG) map where pixel intensity was proportional
to the length of time that adjacent segments matched along a leaf edge. We
investigated the correlation between LEP or TG maps with dose error maps
(obtained by subtracting calculated from either measured (CM) or from re
calculated (CC) data). Re-calculated data were obtained by modifying selected MLC
photon modeling parameters from their commissioned values. We calculated the
correlation coefficient between corresponding regions of CM and CC maps with TG
and LEP maps. A NAT analysis of the CM maps indicated that the NAT index was
minimized for tongue and groove width at the commissioned value of 0.1cm. A
higher correlation coefficient was seen between CM and LEP maps (0.62+/-0.11)
than between CM or CC and TG maps across all MLC modeling parameters used. The
low correlation between both LEP or TG maps and CC maps suggests that the higher
correlation observed between both LEP or TG maps and CM maps cannot be attributed
to the choice of MLC modeling parameters alone. Further work is needed to
pinpoint the cause of this correlation.
PMID- 28512803
TI - Sci-Thurs PM: Delivery-09: Improving megavoltage portal image contrast with low
atomic number target materials.
AB - PURPOSE: to investigate the impact of low atomic number (Z) targets and detector
design on megavoltage (MV) portal image contrast. METHODS AND MATERIALS: two
experimental beams were generated by replacing flattening filtration of a 2100EX
linac with beryllium (Be) and aluminum (Al) targets and using the linac in 6 MeV
electron mode. A standard MV contrast phantom was used to quantify planar image
contrast for the standard 6MV and the 6MeVAl beam, incident on an amorphous
silicon (a-Si) detector. Contrast versus separation for 6MV and 6MeV/Al was
quantified using a 1 cm bone/solid water slab within increasing thicknesses of
solid water. The Monte Carlo BEAMnrc/DOXYZnrc package was used to model beam
generation and detection. The beam/detector model was validated with comparison
to measured open field profiles. RESULTS: Low-Z target spectra differ
significantly from the standard 6MV spectrum with Be-target and Al-target peaks
at ~ 25keV and ~50keV, respectively. Approximately 1/3rd of the photon population
is below 60keV for the 4MeV/Be beam. Planar contrast is increased significantly
over that of 6MV using low-Z targets, showing additional improvement with removal
of the detector's copper build-up layer. Contrast decreases with increasing
separation more rapidly for 6MeV/Al than for 6MV; however contrast for the former
is superior over the full range of separation examined. CONCLUSIONS: Use of low-Z
linac target materials improves MV image contrast. An additional advantage is
realized by removing the copper layer from the a-Si detector. CONFLICT OF
INTEREST: This research has been sponsored by Varian Medical Systems,
Incorporated.
PMID- 28512804
TI - Poster - Thurs Eve-37: Energy and irradiation modality independence of
calibration coefficients for water equivalent plastic scintillation detectors in
the megavoltage range.
AB - PURPOSE: To demonstrate that the independence of the calibration coefficients of
plastic scintillation detector (PSD) for both photon and electron beams in the
megavoltage energy range. METHOD AND MATERIALS: The PSD consists in a small 1 mm
diameter and 2 mm long plastic scintillating fiber made of a polystyrene core
(BCF-12, Saint-Gobain, inc.). The scintillator was coupled to a 2 meters long non
scintillating plastic optical fiber and a color CCD camera (Apogee instruments
inc.) was used as photodetector. The calibration coefficients of the PSD where
extracted for 6 MV, 23 MV photon beams and 9,12,15 and 18 MeV electron beams
using a Farmer ionization chamber (Exradin). Complete removal of the Cerenkov
radiation produced in the optical fiber was performed with a chromatic
discrimination technique using the blue and green channel of the CCD camera. All
measurements were performed according to the recommendations of the AAPM TG-51
protocol for clinical dosimetry. RESULTS: The PSD exhibits a maximum deviation of
less than 1.7 % (about the mean) of its calibration coefficients over the
measured energy range for both irradiation modalities. CONCLUSION: The energy
independence of the calibration coefficients for PSD was demonstrated
experimentally for the first time for both photons and electrons. PSDs have the
potential to simplify and improve accuracy of dose measurements in clinical
situations where photons and electrons are both present in the beam such as
electron contamination in photon beams or bremsstrahlung contaminated electron
beams.
PMID- 28512805
TI - Poster - Thurs Eve-08: Passive shimming optimization of a permanent magnet
structure for a prototype coupled MRI-medical linear accelerator.
AB - The ultimate goal of radiation therapy is to increase tumor control while
reducing normal tissue complications. This is accomplished by conforming the
radiation dose delivered to a patient to the tumor geometry, permitting the
delivery of higher doses to the target volume while decreasing the dose in
surrounding normal tissues. In order to best achieve this goal, our group is
pursuing the design of a 0.2T biplanar magnetic resonance imager (MRI) coupled
with a medical linear accelerator, which will be capable of performing real-time
image guided radiotherapy. In a simplified design of the permanent magnet
structure for this system, large paramagnetic plates which affect the
characteristics of the magnetic field in the imaging volume are used to hold the
magnetic material in place. Since the sole purpose of the MRI module of this unit
is to provide geometrical information regarding the shape and position of the
target volume during irradiation, obtaining distortion-free images is critical.
In the present work, we seek a particular surface topology on the pole plates of
the permanent magnet structure which minimizes the overall size of the pole
plates while maximizing the homogeneity of the magnetic field in the imaging
volume. A rose ring design is investigated with the aid of finite element
analysis and the results indicate that a significant improvement in field
uniformity is obtained as compared to the simplest design possible.
PMID- 28512806
TI - Poster - Thurs Eve-19: IGRT QA for helical tomotherapy.
AB - Helical tomotherapy (HT) with daily imaging using mega-voltage computed
tomography for 3D image guided radiotherapy (IGRT). We present two techniques
developed in our department to verify the integrity of the HT IGRT process. A
phantom was constructed of two equally sized (5*10*10cm3 ) polystyrene blocks
stacked on top of each other, each piece having a hole capable of receiving a
small volume ionization chamber. A piece of Radiochromic film fits neatly in
between the blocks. The phantom was CT scanned and the CT slices were transferred
to the HT treatment planning system (TPS). The first procedure is used daily to
test the image registration aspects of the IGRT process, and involves setting the
phantom on the tomotherapy treatment unit table in an arbitrary position, imaging
it, and performing image registration to determine what displacements are
necessary to return the phantom to the planned position. A variation of this test
is to place the phantom at a position incurring known displacements and ensuring
the registration recognizes the shifts. The second procedure verifies the entire
IGRT procedure, and includes the first procedure and the delivery of a treatment
plan. An inverse plan is created to deliver simultaneously 2 and 3 Gy to 2 pre
defined targets. The treatment plan can be setup as a QA plan in the TPS
software, allowing for a detailed comparison of ion chamber measurements and film
dosimetry to the planned dose distribution. We have found that these QA
procedures adequately test the IGRT capabilities of our HT unit.
PMID- 28512807
TI - Poster - Thurs Eve-30: Investigation of a patient immobilization system for
breast tomotherapy.
AB - Using tomotherapy to deliver adjuvant radiation therapy for breast cancer
treatment requires more precise immobilization than can be achieved using gravity
alone. We evaluated the use of a thermoplastic shell to immobilize the patient's
torso during breast cancer treatment. To measure intrafraction breathing motion,
4DCT scans were performed for eight post-lumpectomy or post-mastectomy breast
cancer patients with the thermoplastic shell in place. The 4DCT scans were then
analyzed to determine the magnitude of motion of the breast surface, chest wall,
and heart over the breathing cycle. Maximum surface motion was typically less
than 2mm, with a maximum of 4mm. Maximum displacement of the chest wall was less
than 3mm with a maximum of 5mm in a single patient. Comparison with the setup
errors recorded prior to repositioning the patients suggests that, with the
thermoplastic shell in place, patient setup error will be a more significant
source of uncertainty in patient position than breathing motion.
PMID- 28512808
TI - Poster - Thurs Eve-21: Experience with the Velocity(TM) pre-commissioning
services.
AB - As the first Canadian users of the VelocityTM program offered by Siemens, we
would like to share our experience with the program. The Velocity program
involves the measurement of the commissioning data by an independent Physics
consulting company at the factory test cell. The data collected was used to model
the treatment beams in our planning system in parallel with the linac delivery
and installation. Beam models and a complete data book were generated for two
photon energies including Virtual Wedge, physical wedge, and IMRT, and 6 electron
energies at 100 and 110 cm SSD. Our final beam models are essentially the
Velocity models with some minor modifications to customize the fit to our liking.
Our experience with the Velocity program was very positive; the data collection
was professional and efficient. It allowed us to proceed with confidence in our
beam data and modeling and to spend more time on other aspects of opening a new
clinic. With the assistance of the program we were able to open a three-linac
clinic with Image-Guided IMRT within 4.5 months of machine delivery.
PMID- 28512809
TI - Sci-Thurs PM: Delivery-04: Comprehensive fluence model for absolute portal dose
image prediction in IMRT pre-treatment verification.
AB - Amorphous silicon (a-Si) electronic portal imaging devices (EPIDs) have been
heavily investigated as treatment verification tools, with a particular focus on
intensity modulated radiation therapy (IMRT). This verification could be
accomplished through a comparison of measured portal images to predicted images.
A general fluence determination for portal dose image prediction would be a great
asset in order to model the complex modulation of IMRT. A physically-based
parameter fluence model was developed by matching multi-leaf collimator defined
predicted images to measured image profiles. The fluence model was composed of a
focal Gaussian and extrafocal Gaussian-like source (Pearson VII). Specific
aspects of the MLCs and secondary collimators were also modeled (eg. jaw and MLC
transmission factors, MLC rounded leaf tips, tongue and groove effect, interleaf
leakage, MLC offsets). The resulting calculated fluence was then convolved with
Monte Carlo generated EPID-specific dose kernels to convert incident fluence to
dose delivered to the EPID. Measured EPID data was obtained with an a-Si EPID for
various MLC-defined fields (1*1 to 20*20 cm2 ) over a range of source-to-imager
distances. These measured profiles were used to determine the fluence model
parameters and the resulting model was tested on prostate and oropharyngeal IMRT
fields. The model predicted the open-field profiles within 2%, 2mm, while the
predicted IMRT fields were generally within 3%, 3mm for at least 96% of the
pixels. This model demonstrates the necessary accuracy needed for IMRT portal
dose image prediction in complex clinical examples (<3%, 3mm) and could be used
for pre-treatment verification.
PMID- 28512810
TI - Poster - Thurs Eve-32: Dose errors related to the treatment couch.
AB - Modern radiotherapy linacs often use carbon fibre for their couch tops due to its
radio translucent properties. Beam attenuation by the couches is often ignored
during planning and MU calculation. This work examines beam attenuation and loss
of "skin sparing" (dose build up region) when various photon beams transit either
the MedTec (Siemens) or Medical Intelligence (Elekta) couches. Additionally,
measured doses were compared to CMS treatment planning system (XiO version
4.33.02) predictions. We found the two couches to have different structures,
resulting in different attenuation signatures as a function of gantry angle. For
normal beam incidence the Siemens and Elekta couches had radiological thicknesses
of 4.5 mm and 6.0 mm, respectively. For a normal incidence 10*10 cm2 6MV beam the
surface dose after couch transmission was 93% vs. 83% for Elekta and Siemens,
respectively. Conversely, the increased mass on the lateral edge of the Siemens
couch resulted in a maximum attenuation (6 MV 5*5 cm2 beams) of 8% compared to 5%
by the Elekta couch. Incorporating the treatment couch as part of the patient
planning CT allowed the CMS TPS model to calculate couch attenuation within 1% of
measurement, except at the very edge of the Siemens couch, where the attenuation
is strongly gantry angle dependent. The CMS beam model was also able to predict
the loss of skin sparing within 1%. In conclusion, the two patient couches are
different, but both can significantly affect patient dose which can be accounted
for in the CMS TPS.
PMID- 28512811
TI - Poster - Thurs Eve-03: Dose verification using a 2D diode array (Mapcheck) for
electron beam modeling, QA and patient customized cutouts.
AB - PURPOSE: To assess a diode detector array (MapCheck) for commissioning, quality
assurance (QA); and patient specific QA for electrons. METHOD AND MATERIALS: 2D
dose information was captured for various depths at several square fields ranging
from 2*2 to 25*25cm2 , and 9 patient customized cutouts using both Mapcheck and a
scanning water phantom. Beam energies of 6, 9, 12, 16 and 20 MeV produced by
Varian linacs were used. The water tank, beam energies and fields were also
modeled on the Pinnacle planning system obtaining dose information. Mapcheck,
water phantom and Pinnacle results were compared. Relative output factors (ROF)
acquired with Mapcheck were compared to an in-house algorithm (JeffIrreg). Inter-
and intra-observer variability was also investigated Results: Profiles and %DD
data for Mapcheck, water tank, and Pinnacle agree well. High-dose, low-dose
gradient comparisons agree to within 1% between Mapcheck and water phantom. Field
size comparisons showed mostly sub-millimeter agreement. ROFs for Mapcheck and
JeffIrreg agreed within 2.0% (mean=0.9%+/-0.6%). CONCLUSION: The current standard
for electron commissioning and QA is the scanning water tank which may be
inefficient. Our results demonstrate that MapCheck can potentially be an
alternative. Also the dose distributions for patient specific electron treatment
require verification. This procedure is particularly challenging when the minimum
dimension across the central axis of the cutout is smaller than the range of the
electrons in question. Mapcheck offers an easy and efficient way of determining
patient dose distributions especially compared to using the alternatives, namely,
ion chamber and film.
PMID- 28512812
TI - Poster - Thurs Eve-14: Linking IGRT data with dose calculation for prostate IMRT
planning.
AB - Internal organ motion was studied for 20 prostate patients who were treated with
IGRT using MV EPI with three gold seeds implanted in the prostate. Prostate
motion was determined from the gold seed displacement relative to bony anatomy
between the EPI and the DRR fraction-to-fraction before any correction was
applied. The patients were planned with a tight 2mm PTV margin for seven-beam
IMRT with prescribed dose of 82 Gy. Treatment planning incorporating organ motion
was done manually by convolving the static dose distribution with patient
specific PDF. A Gaussian PDF is reasonable for modeling geometric uncertainties.
In the anterior and superior directions, dose decreased more than 5% on the edge
of PTV for 5% of the patients. While in inferior direction the dose decreased
more than 5% on the edge of PTV for 15% of the patients. The PTV dose is lower
than 95% prescription dose for 10% of the patient incorporating individual IGRT
data. While for applying group PDF, the dose satisfied the minimum 95% of PTV
dose, so group PDF should not be used for accurate treatment planning evaluation
for individual patients. Static dose distribution is insufficient to assess PTV
coverage. The inclusion of organ motion on dose distribution is required for
close agreement between planned and delivered dose. The Gaussian PDF is patient
specific and group PDF should not be used for accurate treatment planning
evaluation for individual patients. Patient-specific PDF data should be used for
re-planning to assess accuracy of delivered dose.
PMID- 28512813
TI - Poster - Thurs Eve-25: Depth dependence of electron backscatter for electron
radiotherapy: A Monte Carlo study.
AB - The aim of this study is to investigate the depth dependence of electron
backscatter from lead (Pb) for clinical electron beams using Monte Carlo
simulations. Phase-space files for the 4 and 9MeV electron beams based on the
Varian 21EX Linac were generated using the BEAMnrc code. A 3mm Pb layer was
irradiated by the phase-space beams with 0.5 and 1cm depth of water on top.
Electron energy spectra at different depths in water with and without the Pb
layer were determined using the BEAMnrc code. For energy spectra of the 4 MeV
beams with 0.5cm depth of water, electron backscatter was found at both the Pb
water interface and 0.5cm of water over the Pb. However, electron backscatter
almost disappeared at 0.5 and 1cm of water over the Pb, when 1cm depth of water
was used. This is because the increased attenuations of the (1) 4MeV beam from
the thicker water layer, and (2) electron backscatter in water above the Pb. For
the 9MeV beams with 0.5cm depth of water, only slight electron backscatter was
observed. More electron backscatter was found when 1cm depth of water was used.
It is because the electron beam energy was reduced more due to the attenuation of
the 1 cm depth of water compared to 0.5 cm. Since the electron energy spectrum
varies with depth of water on top of the Pb layer, the electron backscatter
depends very much on the thickness of water/water equivalent bolus/human tissue
over the Pb shield in electron radiotherapy.
PMID- 28512814
TI - Sci-Thurs PM: Delivery-08: Investigation of the source of RF noise from a
modulator for an MR-linac project.
AB - INTRODUCTION: The next significant step in the advancement of IGRT is the
integration of an MRI with a linac. The MRI-linac will provide images with
exquisite soft tissue contrast in real-time during treatment. A possible problem
associated with the proposed integration is the RF noise generated by the linac.
This noise could interfere with the received signals of the MRI producing
deleterious effects in the image quality. The work herein is concerned with
understanding the processes involved in the RF noise production and the magnitude
and frequency of this RF noise in the modulator of a linac. MATERIALS/METHODS: A
software programming environment, MultiSIM, was used to model the electronic
components of a modulator. Several Current and Voltage waveforms from the
modulator were measured with an oscilloscope and compared with the corresponding
results from the modulator model for validation. Finally, RF noise generated by
the modulator was measured using field probes, which permits the frequency
components of the measured and simulated modulator waveforms to be compared with
the measured RF noise. RESULTS/DISCUSSION: The modeled PFN charging current and
voltage, and klystron current show good agreement with measurements, with the
exception of the tail of the klystron voltage signal. Once the model has been
validated in both the time and frequency domains, future work will entail
predicting pulse shape changes when, and if, modifications to the modulator are
made. Specifically, modifications will be made which shift and/or reduce the RF
noise in the frequency range of interest for a 0.2T MRI.
PMID- 28512815
TI - Poster - Thurs Eve-36: Use of multileaf collimator as a replacement of physical
missing tissue compensator.
AB - Missing tissue compensators are used to improve dose uniformity for some patients
undergoing radiation therapy. Currently, our practice is to machine compensators
out of lead alloy plate. Replacing this physical filter with a segmented
multileaf collimator (MLC) delivery sequence is beneficial in terms of work flow
and delivery efficiency. The purpose of this work is to compare the dose
uniformity achieved by fields that are either (A) conventionally compensated,
compensated by segmenting the physical compensator thickness map into either (B)
step-and-shoot or (C) dynamic MLC delivery sequences using an in-house sequencer,
(D) compensated using Pinnacle sequencer, or (E) compensated using IMRT
optimization. A computer program was developed to construct both step-and-shoot
and dynamic MLC sequence files from mechanical thickness maps of our current
compensators. In addition, the Pinnacle sequencer and IMRT optimization were used
to generate step-and-shoot MLC sequences. Planar doses were measured for each at
the isocenter depth with an ion chamber array to compare the five methods. A
comparison of the relative dose distribution shows that the compensation achieved
by method (E) is in close agreement with that achieved using method (A), that is,
dose uniformity within 4%. Method (D) resulted in the shortest delivery time and
achieved dose uniformity to within 5%. Methods (B) and (C) need additional
refinement to be of practical use. The results support the feasibility of
replacing physical compensators with MLC delivery sequences. Compensation by MLC
segments provides more flexibility and efficiency in design and delivery than by
physical compensators while maintaining or improving the uniformity of dose to
the plane of compensation.
PMID- 28512816
TI - Poster - Thurs Eve-07: The dosimetric consequences of MLC position inaccuracy in
IMRT.
AB - The Multileaf Collimator (MLC), the most widely used means of intensity
modulating beams for IMRT, is subject to random and systematic errors in leaf
positions that may compromise the treatment quality. This work is a simulation
study of the effect of random and systematic errors in leaf position on delivered
dose distributions. The dosimetric effects of random errors of up to 2 mm and
systematic errors (+/-1mm in 2 banks, +/-0.5mm in 2 banks and 2mm in 1 bank of
leaves) were analysed for a typical head and neck IMRT plan and a typical
prostate IMRT plan. Dose Volume Histograms and Equivalent Uniform Doses (EUD) of
the target volumes, bladder and rectum for the prostate plan and brainstem,
larynx, parotids and spinal cord for the head and neck plan were calculated with
and without MLC positioning errors and compared. The results show that if we
adopt a 2% change in EUD of the target and 2 Gy for the OARs as acceptable levels
of uncertainty in dose due to MLC effects only, then random errors of up to 2mm
may be tolerated but systematic errors in leaf position will need to be limited
to 0.5mm. Our study provides guidance, based on a surrogate of clinical outcome,
for the development of quality control standards for multileaf collimators.
PMID- 28512817
TI - Poster - Thurs Eve-18: Performance evaluation of MV CT imaging on the HI ART II
tomotherapy unit.
AB - The HI-ART II unit (TomoTherapy Inc., Madison WI) is a modality used by the
London Regional Cancer Program (LRCP) for radiation therapy. This machine uses
the same source of Megavoltage energy radiation to image (3.5 MV) and to treat
(6MV) patients, combining the functionality of a traditional linear accelerator
and CT simulator into one unit. Thus, it is possible to assess patient
positioning and adjust for anatomy changes just prior to radiation therapy.
Unfortunately, at MV energy levels, the physics of radiation interaction limits
image quality, and gives rise to an inherent dose limitation concern that
enhances noise levels. Therefore, we propose to quantify the image quality
produced by the HI-ART II unit using techniques established for kVCT scanner
technology. Our study involved the use of three standard phantoms to test image
resolution, noise, uniformity, and linearity for a 512 * 512 reconstruction
matrix and three scan pitch settings (0.8, 1.6, and 2.4). Results follow:
linearity between MV CT number versus relative electron density was observed,
noise calculations ranged from 2.15-2.51%, and a distinct central artifact was
revealed during uniformity testing. The linearity between MV CT number versus
relative electron density implies that MV CT images are highly suitable for dose
calculations. MV CT image quality of uniform phantoms were acceptable and
demonstrated noise levels higher than those produced by kVCT simulators. Further
study is necessary to correct for the central artifact in MV CT images.
PMID- 28512818
TI - Poster - Thurs Eve-29: Real-time tumour tracking and dose adaptation utilizing 4D
MR images.
AB - Magnetic Resonance Imaging (MRI) is known to be the best imaging modality for
soft-tissue delineation. We will exploit this feature to develop and test a real
time tumour tracking and dose adaptation algorithm based on 4D MR images, such as
we hope to obtain using a Linac-MR system under development by our research
group. We have developed algorithms capable of auto-contouring and tracking the
motion of tumours in pseudo real-time from 4D MR image sets acquired 4 times per
second. To compensate for the time delays between imaging, image processing, the
mechanical movement of Linac, and the actual treatment, an algorithm capable of
predictively modeling tumour position based on 4D MR images, such as would be
acquired just prior to patient treatment, is being developed. Based on these, an
algorithm able to adjust Multileaf Collimator (MLC) movement and beam intensity
depending on the position, depth, and density of tissue overlying the tumour as a
function of time is under development. Our initial results, in which we used 4D
MR images acquired from a 3T MR scanner with a Steady State Free Precession
(SSFP) image sequence, demonstrated the feasibility of real-time tumour
contouring and tracking. By using an in-house built MR compatible motion phantom
and the same scanner with a Balanced Full Field Echo (BFFE) image sequence, we
succeeded in acquiring dynamic MR images, and we confirmed the promising
capability of our prediction algorithm, which can infer the position of tumour
0.25 seconds in advance.
PMID- 28512819
TI - Sci-Thurs PM: Delivery-12: Correction and calibration of megavoltage cone-beam CT
images for the calculation of the dose of the day.
AB - PURPOSE: To show that accurate dose calculations can be achieved with megavoltage
cone-beam CT (MVCBCT) images of head-and-neck (H&N) and prostate sites, allowing
the verification of the daily dose distribution received by these patients.
METHOD AND MATERIALS: Corrections for the cupping and missing data artifacts seen
on MVCBCT images were developed for both H&N and pelvic imaging. MVCBCT images of
six H&N and two prostate patients were acquired weekly during the course of their
treatment. Several regions of interest were contoured including: the prostate and
rectum and the spinal cord and parotids. Dose calculation was performed with the
MVCBCT images using the plan beams. Variations from treatment plan dosimetric
endpoints were analyzed. RESULTS: Dose calculations with kVCT and corrected
MVCBCT images of the H&N (pelvic) regions show standard deviations of 1.9%
(0.6%). The mean dose to the right parotid of H&N patients had an average
increase of 18% during treatment. The maximum dose to 1% of the spinal cord went
up by 2% on average. For prostate patients on one fraction the dose received by
95% of the prostate diminished by 3%. One patient had an average increase of 3.6%
of the maximum dose received by 1% of the rectum. CONCLUSION: MVCBCT can be used
to verify daily dose distributions for H&N and prostate patients. An increase in
the mean dose to normal tissues was observed during H&N treatment. Underdosage of
the prostate and the dosimetric consequences of volume changes in rectum and
bladder were observed. Research supported by Siemens.
PMID- 28512820
TI - Poster - Thurs Eve-31: Clinical implementation and experience with EPID-based
precision isocentre localization.
AB - Modern linear accelerators contain multiple isocentres, defined by the mechanical
motions of gantry, collimator and table. Isocentre localization for these motions
has been performed using film and manual evaluations which have difficulty in
relating the individual motions. To address these limitations, we have developed
an EPID based technique to measure the isocentre position for each of the
treatment unit motions. This technique uses the projected position of a radio
opaque marker at the isocentre in a series of MV images to determine the motion
of the isocentre. This analytical procedure has been implemented in the clinic
using a MatLab code to automatically analyze images and determine both the
isocentre position and motion about the mean for each of gantry, collimator and
table. Results of isocentre measurements for 18 machines from 2 different vendors
at 2 separate clinics are reported. These measurements show that while the
position of the mean isocentres are contained within a 2mm sphere, combinations
of gantry, table and collimator rotations can be found that result in treatment
isocentres more than 2mm apart. Results for a treatment unit, which underwent a
recent equipment upgrade, are also presented that show a small change in the
location of the gantry relative to the table isocentre. The implementation of
this of isocentre localization technique has provided important clinical
information which can be efficiently completed in less than an hour. This
information is an important consideration in monitoring the changes and in
assessing the treatment precision that can be obtained.
PMID- 28512821
TI - Poster - Thurs Eve-02: 3 dimensional ultrasound-guided breast brachytherapy.
AB - Breast cancer is one of Canada's leading causes of death, taking the lives of
approximately 5000 people annually. Breast-conserving tumour excision, or
lumpectomy followed by radiation therapy is becoming an increasingly common
treatment method for smaller tumours. High dose rate (HDR) brachytherapy is a
precise form of radiation delivery following surgery involving the delivery of
radiation dose through an HDR afterloader attached to catheters inserted into the
breast. Currently, a CT scan of the patient is taken to properly reconstruct the
tumour and guide catheter insertion. We propose to use our three-dimensional
ultrasound (3DUS) scanner as the primary treatment planning device, eliminating
the need for a CT scan. This would greatly increase patient comfort along with
saving time and money. We have designed and constructed a 3DUS scanner
specifically to be used in breast brachytherapy. It attaches to a Kuske breast
application kit already used in the clinic. Software to view 3DUS images produced
by the device is already being used, and needle guidance software is currently
being developed. Laboratory tests on agar phantoms are set to begin shortly to
evaluate the precision of the device and perform brachytherapy catheter insertion
simulations. When the results of these tests are satisfactory, a full
brachytherapy procedure will be performed in Quebec City using the 3DUS scanner.
PMID- 28512822
TI - Poster - Thurs Eve-13: Modeling the effect of organ motion on cumulative rectal
dose using EUD.
AB - A rigid body model and electronic serial portal imaging (EPI) data were used to
generate the cumulative dose distribution for the rectum incorporating organ
motion during IMRT. The impact of rectal motion was assessed via NTCP and TCP
based on equivalent uniform dose per fraction (EUDf ). The rectal positional
variations were measured fraction-to-fraction from MV EPI for 20 prostate
patients implanted with gold seeds. Five-field (5F) and seven-field (7F) IMRT
plans for prostate patients were constructed with prescribed dose 78 Gy/39
fractions using a Pinnacle3 treatment planning system. EUD increased in 45% of
the patients with greater than 2.5% increase for 5% of the patients. While EUD
decreased in 55% of the patients with greater than 2.5% decrease for 10% of the
patients. The amplitudes of EUDf increase and decrease are correlated with the
dose gradient. Higher dose gradients lead to higher rectal EUDf change. The
rectal NTCP decreases for half of the patients and increases for the other for
both 5F and 7F plans. The NTCP decreased with the increasing of dose gradient
between the prostate and rectum for 5F and 7F IMRT plans. The correlation
coefficient for the rectal NTCP and the dose gradient is - 0.71. The increase or
decrease of rectal cumulative dose depends on the dose gradient, motion amplitude
and frequency in AP direction. EUDf is a useful QA parameter for interpreting the
biological impact of geometric uncertainties on the static dose distribution.
Rectal NTCP is patient dependent and must be determined individually.
PMID- 28512823
TI - Poster - Thurs Eve-24: Dosimetry study on the penumbra region for the irregular
MLC fields with stepping patterns.
AB - The aim of this study is to investigate the dosimetric effect in the penumbra
region for the multi-leaf collimator (MLC) fields with stepping patterns. Various
irregular MLC fields with different stepping patterns were designed. Radiographic
films were used to measure the beam profiles (cross-plane (X1-X2 jaw) and in
plane (Y1-Y2 jaw)) for different MLC field configurations of varying lengths of
protruded leaves adjacent (on one or both sides) to the beam profile axis. 6 MV
photon beams produced by the Varian 21 EX linear accelerator with 120-leaf
Millennium MLC were used. The results showed that the penumbra widths (10% - 90%)
of the profiles (cross-plane) with 0.5 cm gap width increased with the protruded
lengths of the neighbouring leaves, while the penumbra widths did not vary too
much for the larger gap widths of 1 cm and 1.5 cm. The neighbouring leaf's
influence on the profile was very insignificant, when the distance between the
profile and neighbouring leaf edge was larger than 1 cm. Moreover, when both the
upper and lower portions of leaves were moved out forming a gap for the profile,
the dose at the "edge" region was decreased by about 20% and 6% when the
protruded lengths of the leaves were 0.5 cm and 1 cm, respectively. It is
important to understand the dosimetric effect in the penumbra region for
irregular MLC fields with stepping leaf patterns, especially during the
commissioning process for the conformal external beam and intensity modulated
radiation therapy.
PMID- 28512824
TI - Sci-Thurs PM: Delivery-07: Evaluation of prospects to use daily megavoltage CT
studies for adaptive radiotherapy.
AB - PURPOSE: To evaluate gross tumor volume (GTV) changes for non-small cell lung
cancer (NSCLC) patients using daily megavoltage CT (MVCT) studies acquired before
each treatment fraction on helical tomotherapy, and to relate the potential
benefit of adaptive image-guided radiotherapy to changes in GTV. METHODS: 17
patients were prescribed 30 fractions of radiotherapy on helical tomotherapy for
NSCLC at London Regional Cancer Program from December 2005 to March 2007. The GTV
was contoured on the daily MVCT studies of each patient. Adapted plans were
created using merged MVCT-kVCT image sets to investigate the advantages of
replanning for patients with differing GTV regression characteristics. RESULTS:
The average GTV change observed over 30 fractions was -38%, ranging from -12 to
87%. No significant correlation was observed between GTV change and patient's
physical or tumor features. The pattern of GTV changes of the 17 patients could
be broadly divided into 3 groups with distinctive potential for benefit from
adaptive planning. CONCLUSIONS: GTV changes are difficult to predict
quantitatively based on patient or tumor characteristics. If changes do occur,
there are points in time during the treatment course when it may be appropriate
to adapt the plan to improve sparing of normal tissues. If the GTV decreases by
greater than 30% at any point in the first twenty fractions of treatment,
adaptive planning is appropriate to further improve the therapeutic ratio.
PMID- 28512825
TI - Poster - Thurs Eve-35: Error reduction in variable angle implant reconstruction
by optimization of imaging geometry.
AB - Movement towards intraoperative dosimetric analysis of permanent seed
brachytherapy implants has driven seed localization techniques that may be
applied in an operating suite. Variable angle reconstructions with a C-arm are a
widely available, cost effective and easily integrated solution but are subject
to mechanical limitations on imaging geometry accuracy. Phantom reconstructions
of known seed locations were used to show optimization of the imaging geometry
for consistency with the observed datasets in multiple variable angle images can
be used to obtain more accurate source and detector positions and reduce
uncertainty in reconstructed seed positions. Furthermore, the most difficult part
of backprojection methods is the matching of corresponding seeds between the
variable angle images. With improved accuracy in imaging geometry, tighter
constraints on possible seed matches can be used. This reduces the number of
potential matches between images. Application to typical clinical data has shown
a reduction in the number of possible matches. The benefits are observed when
optimizations are performed on very small subsets of matched seeds, allowing a
small number of obvious matches due to orientation or peripheral positioning to
greatly simplify matching over the remainder of the implant.
PMID- 28512826
TI - Poster - Thurs Eve-06: Maximizing eclipse IMRT dose accuracy by adjusting the
dosimetric leaf gap parameter.
AB - The dosimetric leaf gap (DLG) is a parameter used by Eclipse to model the rounded
leaf ends of Varian MLCs. The DLGs were determined for the Millennium (M120) and
High-Definition (HD120) model MLCs and taken as the difference between measured
(0.6mm diode, IBA) and nominal MLC-defined profile FWHM values. Configuring the
Eclipse pencil beam algorithm with the measured DLG gave poor agreement between
measured and calculated IMRT dose distributions for the HD120 but not the M120.
Agreement was optimized by adjusting the DLG for the HD120; 0.3mm changes in DLG
were enough to cause significant variations in field dose agreement. Optimal DLG
values of 0.04cm and 0.05cm were found for the 6MV HD120 and 10MV HD120,
respectively, and 0.135cm 0.175cm for the 6MV M120 and 18MV M120, respectively.
Agreement between measured and calculated dose distributions worsened for the AAA
algorithm indicating separate DLG values may be required. A leaf calibration
software upgrade also reduced agreement by changing the physical leaf position
for a given location value. The change was detected using film and the picket
fence MLC-pattern which places the two banks of opposing leaves at the same
position but at different times. The DLG value can be adjusted from its measured
physical value to improve the dosimetric accuracy of Eclipse IMRT plans and
compensate for the effects of treatment planning algorithm and varying leaf
calibrations. Since leaf calibrations are variable it is important to define the
dosimetric leaf gap for each accelerator and clinic.
PMID- 28512827
TI - Poster - Thurs Eve-17: Stand alone software for deforming delivered dose
distributions to account for daily anatomical variations in prostate patients
treated on the TomoTherapy Hi-Art II system.
AB - The acquisition of daily megavoltage (MV)-CT images provides an invaluable tool
in the delivery of adaptive radiotherapy (ART) on the TomoTherapy Hi-ART II
system. Using TomoTherapy's Planned Adaptive software, delivery sinograms can be
applied to pre-treatment MVCT images to generate daily delivered dose
distributions, allowing for the potential comparison of planned and delivered
doses. However, daily patient anatomical variations complicate the task and
accurate comparison requires that daily doses be evaluated in the same references
frame as the planned dose. Each anatomical point in daily MVCT images must be
mapped to its corresponding point in the patient planning CT and that deformation
map must be applied to the daily dose distribution. Stand alone software has been
developed for the comparison of planned and delivered doses for TomoTherapy
prostate patients. Software inputs are the planning CT, planning structure data,
planned dose distribution, daily MVCT and delivered dose distribution. The
software uses an in-house developed automatic voxel-based deformable registration
algorithm designed and optimized specifically for the registration of prostate CT
images to achieve anatomical correspondence between MVCT and planning images. The
resultant deformation map is applied to the daily dose distribution and the
software outputs the deformed daily dose distribution in the planning CT's
reference frame, as well as a delivered DVH for each of the planning CT's ROI.
The software allows for a number of potential research opportunities, in
particular, the calculation of the cumulative dose delivered over the course of
treatment for prostate patients treated on the Hi-Art II system.
PMID- 28512829
TI - Sci-Thurs PM: Delivery-11: Image guidance for prostate IMRT using low dose cone
beam CT.
AB - Linac-mounted cone beam computed tomography (CBCT) using Varian's On Board Imager
(OBI) currently delivers significant imaging dose and lacks automatic methods for
clinical target volume (CTV) registration. In this work, we address these two
issues to enable frequent treatment corrections during a course of prostate
intensity modulated radiation therapy (IMRT). The process starts by acquiring a
low dose (low mAs) CBCT image after patient setup. The image is then used in one
of two automatic image guidance strategies. The "global" technique provides the
couch corrections necessary to improve patient setup by registering the CBCT to
the planning CT. The "local" method involves non-rigid registration of the
planning CT to the CBCT followed by automatic treatment re-optimization using the
deformed planning CT and contours. Thus, the global method attempts to correct
patient setup to match the planned treatment, while the local method corrects the
treatment to match the patient setup. Both techniques were evaluated using images
of an anthropomorphic male pelvis phantom. Global image guidance resulted in a
registration error of 3.6 +/- 1.3 mm (imaging dose independent) and high
treatment doses to the bladder and rectum for large magnitude motion. The local
technique always resulted in clinically acceptable treatment doses due to a
reduced registration error of 2.3 +/- 0.8 mm, obtained at 15% of the OBI's
default dose (125 kVp, 2 mAs per projection). These preliminary results show that
our automatic local image guidance technique reduces imaging dose and is
sufficiently accurate and robust for application in prostate IMRT.
PMID- 28512828
TI - Poster - Thurs Eve-28: New brain diffusion analysis method: White matter grey
matter dissasociation.
AB - Diffusion MR studies are often used to investigate the physical properties of
brain tissues (1, 2). It is known that a full characterisation of the diffusion
decay for brain could give valuable information about the structural organisation
of cerebral tissue. The significance of the present diffusion decay study lies in
the combination of three novel procedures to provide a better characterization of
the diffusion decay: i) the acquisition of a large number of b-values (96 b
values up to 10,000 s/mm2 ), ii) the application of a noise correction technique
(3) to the acquired data, and iii) the use of a Non Negative Least Squares (NNLS)
fitting algorithm to evaluate the diffusion coefficients. The presence of noise
in magnitude MR images can affect the calculation of the diffusion parameters (4)
and therefore a noise correction technique (3) is applied. The NNLS algorithm is
used to fit the corrected data instead of the more commonly used Levenberg
Marquardt algorithm since the NNLS algorithm does not require the number of
components to be specified, nor does it need initial estimates of the fitting
parameters as input; thus giving it more versatility as a fitting tool for the
diffusion decay. The results indicate that the diffusion decays in grey and white
matter have one and two components, respectively. Consequently, the short
diffusion component in white matter (Fig. 1.c) can be used as a tool in the
disassociation of white and grey matter tissues.
PMID- 28512830
TI - Poster - Thurs Eve-10: The accuracy of MU calculations for enhanced dynamic wedge
with the Varian's anisotropic analytical algorithm.
AB - The Anisotropic Analytical Algorithm (AAA) of the Varian Eclipse treatment
planning system calculates absolute dose for a variety of beam settings including
those with an enhanced dynamic wedge (EDW). This algorithm has gone through a
number of version updates since it was first released in July 2005. Previous
versions of AAA have come with instructions on how to manually modify the several
parameters that affect the EDW output factors. The current version of AAA
(8.1.17) has had the EDW module modified so that problems associated with the
second-source parameter calculation are resolved. The purpose of this paper is to
report on the observed discrepancies between measured and calculated EDW output
factors for the current version (8.1.17) and the most recent version (8.0.05) of
the AAA algorithm. EDW output factors were measured in a water-equivalent phantom
on a Varian 2100iX LINAC running 6MV and 15MV photon beams. A similar geometry
was modelled in the treatment planning system to calculate the number of monitor
units required to deliver a specified dose at a depth with or without an EDW.
Measurements and calculations were performed for a wide range of EDW wedge
angles, field sizes and depths. The best EDW output factor results possible with
version 8.0.05 yielded discrepancies up to 7% despite considerable parameter
adjustment. The new version (8.1.17) gave results within 1% of measured without
any parameter adjustment. Care should be taken when using any Eclipse AAA
algorithm earlier than version 8.1.17 to calculate MUs for Varian enhanced
dynamic wedge.
PMID- 28512831
TI - Poster - Thurs Eve-01: Comparison of clinical IMRT plan quality and delivery
accuracy: Few large segments vs many small segments.
AB - Commercial radiation treatment planning systems for intensity modulation use
optimization algorithms that can vary multi-leaf collimator (MLC) segment sizes,
segment number and the minimum number of monitor units (MU) per segment. These
parameters are varied according to the treatment site, size, location, and
proximity to the organs at risk. This study compares the utility of optimization
using (Case A) few large segments and a higher minimum MU per segment to that of
(case B) using many smaller segments with a lower minimum MU per segment. For
Case A, the patient benefits from a reduced treatment time associated with fewer
MUs and fewer MLC movements and an increased accuracy in dose delivery. Also,
shorter treatment times may lead to fewer patient movement uncertainties. The
accumulated MLC leakage dose is reduced, the patient specific quality assurance
(QA) is more manageable and small field modeling inaccuracies are reduced.
Pinnacle-3 (v8) plans are generated with direct machine parameter optimization
(DMPO) for both scenarios. Three dimensional dose distributions and dose volume
histograms are used to compare plan quality. We compare plans using few large MLC
segments with those using many small MLC segments for some clinical cases.
Improved plan quality is demonstrated using fewer MLC segments. Dose QAs are
performed and compared for each scenario using MapCheck and film. When comparing
dose delivery accuracy between different MU per segment settings, a decrease in
delivery errors with minimum MU size is observed. In conclusion, few large MLC
segments with larger area should be used when possible.
PMID- 28512832
TI - Poster - Thurs Eve-12: A needle-positioning robot co-registered with volumetric x
ray micro-computed tomography images for minimally-invasive small-animal
interventions.
AB - Preclinical research protocols often require the delivery of biological
substances to specific targets in small animal disease models. To target
biologically relevant locations in mice accurately, the needle positioning error
needs to be < 200 MUm. If targeting is inaccurate, experimental results can be
inconclusive or misleading. We have developed a robotic manipulator that is
capable of positioning a needle with a mean error < 100 MUm. An apparatus and
method were developed for integrating the needle-positioning robot with
volumetric micro-computed tomography image guidance for interventions in small
animals. Accurate image-to-robot registration is critical for integration as it
enables targets identified in the image to be mapped to physical coordinates
inside the animal. Registration is accomplished by injecting barium sulphate into
needle tracks as the robot withdraws the needle from target points in a tissue
mimicking phantom. Registration accuracy is therefore affected by the positioning
error of the robot and is assessed by measuring the point-to-line fiducial and
target registration errors (FRE, TRE). Centroid points along cross-sectional
slices of the track are determined using region growing segmentation followed by
application of a center-of-mass algorithm. The centerline points are registered
to needle trajectories in robot coordinates by applying an iterative closest
point algorithm between points and lines. Implementing this procedure with four
fiducial needle tracks produced a point-to-line FRE and TRE of 246 +/- 58 MUm and
194 +/- 18 MUm, respectively. The proposed registration technique produced a TRE
< 200 MUm, in the presence of robot positioning error, meeting design
specification.
PMID- 28512833
TI - Poster - Thurs Eve-23: Effect of lung density and geometry variation on
inhomogeneity correction algorithms: A Monte Carlo dosimetry evaluation.
AB - This study provides new information on the evaluation of the lung dose
calculation algorithms as a function of the relative electron density of lung,
rhoe,lung . Doses calculated using the collapsed cone convolution (CCC) and
adaptive convolution (AC) algorithm in lung with the Pinnacle3 system were
compared to those calculated using the Monte Carlo (MC) simulation (EGSnrc-based
code). Three groups of lung phantoms, namely, "Slab", "Column" and "Cube" with
different rhoe,lung (0.05-0.7), positions, volumes and shapes of lung in water
were used. 6 and 18MV photon beams with 4*4 and 10*10cm2 field sizes produced by
a Varian 21EX Linac were used in the MC dose calculations. Results show that the
CCC algorithm agrees well with AC to within +/-1% for doses calculated in the
lung phantoms, indicating that the AC, with 3-4 times less computing time
required than CCC, is a good substitute for the CCC method. Comparing the CCC and
AC with MC, dose deviations are found when rhoe,lung are ?0.1-0.3. The degree of
deviation depends on the photon beam energy and field size, and is relatively
large when high-energy photon beams with small field are used. For the penumbra
widths (20%-80%), the CCC and AC agree well with MC for the "Slab" and "Cube"
phantoms with the lung volumes at the central beam axis (CAX). However,
deviations >2mm occur in the "Column" phantoms, with two lung volumes separated
by a water column along the CAX, using the 18MV (4*4cm2 ) photon beams with
rhoe,lung ?0.1.
PMID- 28512834
TI - Sci-Thurs PM: Delivery-06: 2-D lag and response nonlinearity corrections for
dynamic IMRT verification using an EPID.
AB - In recent years, EPIDs have been used for pre-treatment IMRT verification.
Although EPID lag and signal nonlinearities have been investigated, they have not
been implemented in the verification process. In dynamic sliding-window IMRT
delivery, the dose delivered, and the time between the end of dose delivery and
the end of image acquisition differ between pixels. The resulting differences in
lag and signal-response across the image can cause artificial asymmetries and
amplitude changes in measured EPID dose images. These artifacts alter the
agreement between measured and predicted images, potentially complicating the
assessment of clinical IMRT verifications. A method of 2-D (pixel-by-pixel)
correction was developed based on data from sets of experiments performed to
independently quantify the lag and nonlinearity characteristics of Varian's aS500
EPID. To test the correction, it was applied to two sweeping window 10*10 cm2
fields that differ only in sweeping direction. The correction resolved
discrepancies in the symmetry between these two cases, and the differences
between measured and predicted amplitudes evident when small numbers of MUs were
delivered. To illustrate its potential use, the correction technique was applied
to a measured image of a clinical IMRT field that produced a relatively poor
verification result. The correction partially accounted for discrepancies between
measured and Eclipse-predicted images of this field, reducing the percentage of
pixels failing a Gamma analysis (3 %, 3 mm) from 8.5 to 5.6 %. This correction
technique can be used to help resolve the source of discrepancies in troublesome
clinical IMRT verifications.
PMID- 28512835
TI - Poster - Thurs Eve-34: Extended CT-range in RT planning of pelvic cancer
treatment in presence of hip replacements.
AB - Extended CT range in conventional CT scanners has a potential to allow for a more
conformal treatment of patients with hip prosthesis. Its use may limit
inaccuracies in electron density maps that are observed due to severe artifacts
in CT data. In this study, we investigate the use of CT images with extended CT
numbers in dose calculations and compare the results of calculations with
standard CT data and measured doses. A phantom containing a hip prosthesis was
scanned and treatment was planned with extended and standard CT numbers. The
density override function was used to eliminate the effect of artifacts in the
region outside of the metallic implant, while raw CT numbers were used to
indicate density within the implant. Dose measurements were performed with two
types of ion chambers at 6, 10 and 18MV energies. Our results indicate that data
with extended CT range result in a better agreement between measured and
calculated dose at the central position of the body phantom, as should be
expected. However, CT artifacts within the implant region also result in
discrepancies between the measured and calculated dose. The discrepancy is
greater at lower cross-sectional thickness where bright, high density surface
artifacts are high relative to the artificially low density inner region of the
implant. Potential ways of resolving the discrepancies are outlined and a
possibility of their application to clinical routine will be discussed.
PMID- 28512836
TI - Poster - Thurs Eve-05: An assessment of PDDs and outputs predicted by a Monte
Carlo-based treatment planning system for electron beams.
AB - Monte Carlo simulation is currently considered to be the most accurate method of
calculating dose distributions for electron beam therapy, and commercial
treatment planning software using simplified macro Monte Carlo is available for
electron treatment planning. In this work, Eclipse V8.1.18 is being investigated
in preparation for the clinical use of CT-based electron treatment planning.
Water tank measurements of percentage depth doses (PDDs) and absolute outputs at
depth of maximum dose (Zmax ) under different geometric conditions are compared
to the results calculated by Eclipse. The measurements are carried out for a
range of electron energies (6, 9, 12, and 16 MeV) for the standard open field
(10*10 cm2 ) and for circular cutouts (2, 3, and 6 cm diameters) at SSD of 100
cm. In addition, extended SSDs (105 and 110 cm) and oblique beam incident (gantry
345 degree) for the open field and 3 cm diameter cutout are measured and compared
to Eclipse. For PDDs, the results predicted by Eclipse are generally acceptable,
falling mostly within 5% of those measured in water. For output, the results
predicted by Eclipse are similar, falling mostly within 3% of those measured in
water. We observed the greatest differences between Eclipse and measurements near
the water surface and in high dose gradients for PDDs. A similar observation is
noted for a small field in the case of outputs.
PMID- 28512837
TI - Poster - Thurs Eve-16: Just-in-time tomography (JiTT).
AB - Soft-tissue target motion is one of the main concerns in high-precision radiation
therapy. Cone beam computed tomography (CBCT) has been developed recently to
image soft-tissue targets in the treatment room for image-guided radiation
therapy. However, due to its relatively long image acquisition time the CBCT
approach cannot provide images of the target at the instant of the treatment and
thus is not adequate for imaging targets with intrafraction motion. In this work,
a new concept for image-guided radiation therapy- just-in-time tomography (JiTT)
is introduced. Differing from CBCT, JiTT takes much less time to generate the
needed tomographical, beam's-eye-view images of the treatment target at the right
moment to guide the radiation therapy treatment. A system to achieve JiTT is
proposed and its feasibility is investigated. Research supported by Siemens.
PMID- 28512838
TI - Poster - Thurs Eve-27: Method of estimating imaging dose to patients from on-line
cone-beam computed tomography using patient size data.
AB - The use of on-line kilovoltage cone-beam computed tomography (CBCT) is increasing
as part of the current evolution of image-guided radiotherapy. At our
institution, we use Varian's On Board Imager(r) (OBI) mainly for imaging prostate
cancer patients. Since daily CBCT can add significant dose, we have performed a
comprehensive set of dose measurements using acrylic cylindrical phantoms using
ionization chambers as well as skin dose measurements using Thermoluminescence
Dosimeters (TLD). The TLD were calibrated under chosen reference conditions
(10*10 cm2 field size at 100 cm SSD) using the OBI beam with bowtie filters (125
kVp, 6.0 mm Al). For the patients, TLD were placed on the anterior, left and
right lateral locations to give the peripheral dose. The CBCT dose values (in
units of mGy/100mAs) were then used to model the central (phantom only) and
peripheral dose (phantom and patients) as a function of equivalent diameter, deq
, using exponential functions. Dose values measured in Rando phantom as well as
published dose values agreed with the model quite well for deq ? 24 cm (body),
but there was higher variation in CBCT dose for deq ? 18 cm (head). Hence, it is
recommended that skin dose be measured for head scans to validate the estimate.
This method provides a quick estimate of CBCT dose so that a decision can be made
whether to incorporate it into the treatment prescription. Also, knowledge of
CBCT dose as a function of patient size may enable reduction of the total mAs for
smaller body scans.
PMID- 28512839
TI - Sci-Thurs PM: Delivery-10: Marker trajectory reconstruction using cone-beam CT
projection images.
AB - Image guidance and daily verification is becoming increasingly important in
radiotherapy today, especially when dealing with moving targets. Cone-beam CT
(CBCT) is a 3D imaging modality available in the treatment room, but it is
difficult to assess motion from this integrated image. If a fiducial marker is
placed in a moving target, it can easily be identified in the raw projection
images that are captured during the CBCT. Normally, this projection data is
discarded after reconstruction, but we show a method that can be used to extract
trajectory information from this data. A CBCT was acquired of a moveable phantom
with a known motion and an implanted gold seed. During the scan, the phantom
underwent 14 cycles of motion. The fiducial marker location was determined from
each raw projection image, and the data was separated into individual breathing
cycles. Each point in each cycle was then assigned a 'breath phase' based
temporal position in the cycle. To reconstruct a single 3D position in room
coordinates, two nearly orthogonal images at the same 'breath phase' but in two
different breaths were used. Multiple reconstructions from 14 nearly orthogonal
pairs produced points which on average should represent the 4D trajectory. When
compared to the true motion, the reconstructed average trajectory had an accuracy
of less than 1mm. We have shown that in the ideal case of identical motion in
each cycle we can accurately measure the 4D trajectory. Future work will use this
tool to collect and estimate the trajectories for more realistic motions which
differ from cycle to cycle.
PMID- 28512840
TI - Poster - Thurs Eve-38: CT Imaging in high dose rate brachytherapy for treatment
of cervical cancer: Estimation of dose to bowel.
AB - Treatment of cervical cancer often involves intracavitary high dose rate (HDR)
brachytherapy. Dose delivered to the bladder and rectum are typically estimated
using the ICRU reference points. Dose to the sigmoid and small bowel are not
estimated, yet these organs typically exhibit significant complication rates. The
objective of this study was to estimate dose to the small bowel and sigmoid using
CT images. Bladder and rectum dose estimates obtained from the reference point
method were also compared to those obtained from CT images. Eighteen CT scans
taken before or after treatment of women treated with HDR using ring and tandem
applicators were included in this study. The small bowel, sigmoid, bladder and
rectum were contoured and the ICRU points were digitized. The minimum dose to 2cc
(D2cc ) of each organ was calculated and normalized to % prescribed to Point A.
Average D2cc bowel dose was 70%. D2cc bowel dose was significantly higher than
both D2cc rectal (27%) and D2cc sigmoid (31%) doses. The average D2cc bladder and
rectal doses were 68% (p=NS) and 27% (p<0.001) of prescribed Point A dose. D2cc
bowel dose, although significantly higher than rectum and sigmoid, is within an
acceptable limit. D2cc bladder and rectum values are either not significantly
different from or are significantly lower than ICRU reference values. The results
of this study suggest that CT imaging is not necessary for determination of dose
to organs at risk. However, image guidance is of value for identifying
perforations prior to commencing treatment.
PMID- 28512841
TI - Poster - Thurs Eve-09: Evaluation of a commercial 2D ion-chamber array for
intensity modulated radiation therapy dose measurements.
AB - Experimental verification of calculated dose from a treatment planning system is
often essential for quality assurance (QA) of intensity modulated radiation
therapy (IMRT). Film dosimetry and single ion chamber measurements are commonly
used for IMRT QA. Film dosimetry has very good spatial resolution, but is labor
intensive and absolute dose is not reliable. Ion chamber measurements are still
required for absolute dose after measurements using films. Dosimeters based on 2D
detector arrays that can measure 2D dose in real-time are gaining wider use.
These devices provide a much easier and reliable tool for IMRT QA. We report the
evaluation of a commercial 2D ion chamber array, including its basic performance
characteristics, such as linearity, reproducibility and uniformity of relative
ion chamber sensitivities, and comparisons between measured 2D dose and
calculated dose with a commercial treatment planning system. Our analysis shows
this matrix has excellent linearity and reproducibility, but relative
sensitivities are tilted such that the +Y region is over sensitive, while the -Y
region is under sensitive. Despite this behavior, our results show good agreement
between measured 2D dose profiles and Eclipse planned data for IMRT test plans
and a few verification plans for clinical breast field-in-field plans. The gamma
values (3% or 3 mm distance-to-agreement) are all less than 1 except for one or
two pixels at the field edge This device provides a fast and reliable stand-alone
dosimeter for IMRT QA.
PMID- 28512842
TI - Poster - Thurs Eve-20: Analysis of dosimetric differences between dose-to-water
vs. dose-to-medium calculations for electron beams.
AB - PURPOSE: With the advent of commercial Monte Carlo based treatment planning
systems (TPS) typically calculating dose-to-medium, Dm , as opposed to dose-to
water, Dw , calculated by conventional TPS, a thorough analysis of differences
between these treatments plans is required. Such an analysis has not yet been
carried out. The purpose of our study was to evaluate dosimetric differences
between such plans generated with a commercial MC based TPS. MATERIALS AND
METHODS: The analysis included plans of 53 breast cancer patients treated with
electron beams ranging from 6-20 MeV. These plans were originally calculated
using the Dm approach. Keeping the original beam arrangements and the same
calculation parameters, the plans were recalculated using the Dw approach. The
comparison between Dm and Dw plans was performed by means of dose volume
histograms and isodose distributions on the corresponding CT slices. RESULTS AND
CONCLUSIONS: The plans calculated using Dm vs. Dw show some differences, with
magnitudes depending on the location of the tumor and organs at risk and the beam
energy. The largest difference was found for the treatment of the chest wall
after complete mastectomy with 13 MeV beam. The dose to internal mammary nodes
was 43.6 Gy and 39.0 Gy for Dm and Dw approach, respectively. This amounts to
8.1% difference in the maximum dose delivered to that volume. For the same
patient, the dose received by the right lung was 13.5 and 15.4 Gy for Dm and Dw
approach, respectively, which amounts to 3.6% difference in dose delivered to
this lung.
PMID- 28512843
TI - Assessment of the efficacy and safety of a new complex skin cream in Asian women:
A controlled clinical trial.
AB - BACKGROUND: Medical products such as hydroquinone and tretinoin have been widely
used to treat various types of skin hyperpigmentation. However, these products
are limited in daily use given their adverse effects. Other alternative agents
with fewer adverse side effects have been developed. However, single agents often
do not produce satisfactory results. AIMS: To evaluate the efficacy and safety of
a new brightening complex cream containing niacinamide, tranexamic acid,
oxyresveratrol, glutathione disulfide, and linoleic acid. PATIENTS AND METHODS: A
total of 26 Korean women seeking to lighten their skin were enrolled. The product
was applied on the face two times per day for 12 weeks. Standardized photographs
were taken at baseline, 4 weeks, 8 weeks, and 12 weeks. Efficacy was assessed
using melanin index (MI), erythema index (EI), and chromatic aberration values
(L*, a*, and b*). Improvement perceived by investigators and patients was
measured as well. RESULTS: The L*-value was increased at 8 weeks (0.7+/-2.5,
P<.05) and at 12 weeks (0.8+/-2.5, P<.05). The MI was significantly decreased at
8 weeks (-4.2+/-4.5, P<.05) and at 12 weeks (-3.8+/-4.8, P<.001). The EI was
significantly improved at 12 weeks (-3.2+/-2.2, P<.001). More than 80% of
patients were considered improved at 12 weeks based on the view of the
investigators and patients. CONCLUSIONS: The new brightening complex cream was
proved to be effective and safe in Asian women.
PMID- 28512845
TI - Work, retirement, and muscle strength loss in old age.
AB - Reduced muscle strength is an accurate predictor of functional limitations,
disability, and mortality. Hence, understanding which socio-economic factors
contribute to preserve muscle strength in old age is central to the design of
social policies that help reducing these health risks. Using data on handgrip
strength collected by the Survey of Health, Ageing and Retirement in Europe for
the population of Europeans aged 50+ and the exogenous variation in pension
eligibility age across countries over time, we estimate that the retirement
transition has a short-term positive causal effect on muscle strength. However,
this protective effect is not persistent, as retirement speeds up the age-related
trend in muscle strength loss, especially for blue-collar workers and males. The
"holy grail" of early retirement may not be such a good deal for retirees'
longevity and physical functioning late in life.
PMID- 28512846
TI - Melatonin influences the sonic hedgehog signaling pathway in porcine cumulus
oocyte complexes.
AB - Melatonin, which is synthesized in the pineal gland and peripheral reproductive
organs, has antioxidant properties and regulates physiological processes. It is
well known that melatonin affects in vitro maturation (IVM) of oocytes and
embryonic development in many species. However, beneficial effects of melatonin
on IVM have been explained mainly by indirect antioxidant effects and little
information is available on the underlying mechanism by which melatonin directly
acts on porcine cumulus oocyte complexes (COCs). Sonic hedgehog (Shh) signaling
is important for follicle development, oocyte maturation, and embryo development,
and there may be a relationship between melatonin and Shh signaling. To examine
this, we designed three groups: (i) control, (ii) melatonin (10-9 mol/L), and
(iii) melatonin with cyclopamine (2 MUmol/L; Shh signaling inhibitor). The aim of
this study was to investigate the effects of these agents on cumulus expansion,
oocyte maturation, embryo development after parthenogenetic activation (PA), gene
expression in cumulus cells, oocytes and blastocysts, and protein expression in
COCs. Melatonin significantly increased the proportion of COCs exhibiting
complete cumulus expansion (degree 4), PA blastocyst formation rates, and total
cell numbers, which were inhibited by addition of cyclopamine. Simultaneously,
the expression of cumulus expansion-related genes (Ptgs1, Ptgs2, and Has2) and
Shh signaling-related genes (Shh, Pthc1, Smo, and Gli1) and proteins (Ptch1, Smo,
and Gli1) in cumulus cells was upregulated in the melatonin-treated group, and
these effects were also inhibited by cyclopamine. In conclusion, our results
suggest that Shh signaling mediates effects of melatonin to improve porcine
cumulus expansion and subsequent embryo development.
PMID- 28512848
TI - Bullous fixed drug eruption due to fluconazole, imitating herpes simplex.
PMID- 28512849
TI - Synthesis and luminescence properties of brick-shaped lanthanum-organic
frameworks with mesoporous and macroporous architectures.
AB - Generally, metal-organic frameworks (MOFs) are made up from kinds of repeating
microporous structure. Here, a series of Eu3+ ions activated terephthalate-based
lanthanum-organic frameworks (La-MOFs) was synthesized by a hydrothermal
reaction. By controlling the reaction time, we obtained some unique brick-shaped
La-MOFs in a micron scale size range, and these La-MOFs showed tunable mesoporous
and macroporous architectures. It is speculated that the change in the
composition and structure of building units results in the formation of this
mesoporous and macroporous heterogeneous architectures. Powder X-ray diffraction
patterns and Eu3+ luminescence behavior support the speculation.
PMID- 28512851
TI - Rebuttal to Dr Bianchi Commentary.
PMID- 28512850
TI - In situ handheld three-dimensional bioprinting for cartilage regeneration.
AB - Articular cartilage injuries experienced at an early age can lead to the
development of osteoarthritis later in life. In situ three-dimensional (3D)
printing is an exciting and innovative biofabrication technology that enables the
surgeon to deliver tissue-engineering techniques at the time and location of
need. We have created a hand-held 3D printing device (biopen) that allows the
simultaneous coaxial extrusion of bioscaffold and cultured cells directly into
the cartilage defect in vivo in a single-session surgery. This pilot study
assessed the ability of the biopen to repair a full-thickness chondral defect and
the early outcomes in cartilage regeneration, and compared these results with
other treatments in a large animal model. A standardized critical-sized full
thickness chondral defect was created in the weight-bearing surface of the
lateral and medial condyles of both femurs of six sheep. Each defect was treated
with one of the following treatments: (i) hand-held in situ 3D printed
bioscaffold using the biopen (HH group), (ii) preconstructed bench-based printed
bioscaffolds (BB group), (iii) microfractures (MF group) or (iv) untreated
(control, C group). At 8 weeks after surgery, macroscopic, microscopic and
biomechanical tests were performed. Surgical 3D bioprinting was performed in all
animals without any intra- or postoperative complication. The HH biopen allowed
early cartilage regeneration. The results of this study show that real-time, in
vivo bioprinting with cells and scaffold is a feasible means of delivering a
regenerative medicine strategy in a large animal model to regenerate articular
cartilage.
PMID- 28512852
TI - Sleep in mental disorders, ageing and memory, insomnia, external factors on sleep
and basic research.
PMID- 28512853
TI - Derivation and validation of the APPEND score: an acute appendicitis clinical
prediction rule.
AB - BACKGROUND: Although many clinical prediction rules (CPRs) for appendicitis
exist, none have been developed for a New Zealand population presenting with
right iliac fossa (RIF) pain. The aim of this study was to derive and validate an
appendicitis CPR for our population. METHOD: This is a retrospective review of
all patients from December 2010 to February 2012 of at least 15 years of age
presenting to the general surgery service with RIF pain. Patient data were
divided into derivation and validation groups. Univariate and multiple regression
analyses identified significant predictors of appendicitis which were used to
construct a CPR. A retrospective validation study was then performed and the CPR
was refined accordingly. Finally, the accuracy of the CPR was tested. RESULTS:
The final components of the new CPR, the APPEND score, were Anorexia, migratory
Pain, local Peritonism, Elevated C-reactive protein, Neutrophilia and male gender
(Dude). This CPR has an area under the receiver operating characteristic curve of
0.84. The CPR can stratify patients into low, intermediate and high-risk groups
which may standardize patient care and reduce the negative appendicectomy rate.
CONCLUSION: A new CPR for predicting appendicitis, in patients presenting with
RIF pain, has been derived and validated for use in our population. A prospective
study to further evaluate its performance is required.
PMID- 28512854
TI - Mogroside IIIE Attenuates LPS-Induced Acute Lung Injury in Mice Partly Through
Regulation of the TLR4/MAPK/NF-kappaB Axis via AMPK Activation.
AB - Acute lung injury (ALI) often leads to high mortality, and there is as yet no
effective drug treatment. The present study aimed to investigate protective
effects of mogroside IIIE (MGIIIE, a cucurbitane-type triterpenoid from Siraitia
grosvenorii Fruits) in experimental ALI and its underlying mechanism. MGIIIE (1,
10 0r 20 mg/kg) was orally administered for 1 h before a single intratracheal
administration of lipopolysaccharide (LPS, 5 mg/kg). MGIIIE treatment dose
dependently suppressed pulmonary oedema, pro-inflammatory mediators (IL-1beta, IL
6, TNF-alpha and HMGB1) release and higher MPO activity in lung tissues induced
by LPS challenge. Molecular researches showed that mogroside IIIE (20 mg/kg) not
only increased the phosphorylation of adenosine 5'-monophosphate-activated
protein kinase (AMPK) but suppressed the over-expression of toll-like receptor 4
(TLR4) and myeloid differentiation factor 88 (MyD88). In addition, MGIIIE also
inhibited the activation of MAPKs and nuclear factor kappaB (NF-kappaB)
signalling in lung tissues from LPS-challenged mice. Similar antiinflammatory
effects of MGIIIE were obtained in LPS-treated macrophages. Compound C (a
pharmacological AMPK inhibitor) obviously reversed the antiinflammatory effect of
MGIIIE in LPS-induced ALI mice. Taken together, AMPK activation plays a crucial
role in the antiinflammatory effects of MGIIIE in LPS-induced ALI by down
regulating TLR4/MAPK/NF-kappaB signalling pathways. Copyright (c) 2017 John Wiley
& Sons, Ltd.
PMID- 28512855
TI - Insulin-like growth factor I enhances the developmental competence of yak embryos
by modulating aquaporin 3.
AB - The objective of our present study was to determine the effects of insulin-like
growth factor I (IGF-I) on the development of yak (Bos grunniens) embryos after
cumulus-oocyte complex (COC) vitrification and warming followed by in vitro
fertilization (IVF). In Experiment 1, the yak COCs underwent vitrification and
then IVF. Embryos were incubated in synthetic oviductal fluid (SOF) supplemented
with four concentrations (0, 50, 100 and 200 ng/ml) of IGF-I, while the yak COCs
without vitrification or IGF-I supplementation acted as the control group; the
BAX, BCL-2, AQP3mRNA and aquaporin 3 (AQP3) protein expression levels in the five
groups of blastocysts were evaluated using quantitative real-time PCR and
immunofluorescence analyses. In Experiment 2, the groups described above were
fertilized and incubated. The cleavage rate, blastocyst rate, total cell count
per blastocyst and the rate of growth of the inner cell mass (ICM) and
trophectoderm (TE) were evaluated. The results were as follows: (1) the AQP3 gene
expression and protein expression in the control and 100 ng/ml IGF-I treatment
groups were the highest. (2) The BAX gene expression was the lowest and the BCL-2
gene expression was the highest in the control and 100 ng/ml IGF-I treatment
groups. (3) The rates of cleavage and blastocysts in the control and 100 ng/ml
IGF-I groups were higher than those in the other three groups. The total cell
count per blastocyst in the vitrified and warmed 100 ng/ml IGF-I group (106.7 +/-
4.9) and the control group (107.3 +/- 4.2) was higher than that in the vitrified
and warmed 0 ng/ml IGF-I (91.2 +/- 3.1), 50 ng/ml IGF-I (92.3 +/- 3.7) and 200
ng/ml IGF-I (92.4 +/- 3.7) groups. Therefore, we conclude that IGF-I can improve
yak blastocyst developmental ability, cytomembrane permeability and formation of
the blastocyst cavity after COC vitrification by improving the BAX, BCL-2 and
AQP3 expression levels.
PMID- 28512856
TI - Early-onset urticaria: a marker of cryopyrin-associated periodic syndrome.
PMID- 28512857
TI - Interest of variations in microRNA-152 and -122 in a series of hepatocellular
carcinomas related to hepatitis C virus infection.
AB - AIM: Hepatocellular carcinoma (HCC) is a common outcome of chronic hepatitis C
virus (HCV) infection and constitutes the main burden of this disease. The
molecular mechanisms underlying the development of HCC are multiple and might
involve certain microRNA (miR). As discordant results have been reported
concerning the detection of expression of miR-152 and miR-122 in HCC, our aim was
to measure the levels of both miRs in serum and liver samples. METHODS: We
analyzed miR-152 and miR-122 expression by reverse transcription-quantitative
polymerase chain reaction in a serum cohort from 14 HCV-infected patients who
developed HCC, 20 HCV+ patients without HCC, and 19 control patients. We also
studied miR-152 and miR-122 in an independent tissue cohort from 11 normal
livers, and from paired HCC and non-tumor adjacent livers of 11 HCV-infected
patients and 12 non-infected patients. RESULTS: In serum samples, higher levels
of miR-122 were found in non-HCC HCV+ compared to HCC HCV+ and control groups,
whereas miR-152 was detectable in a lower range in HCC HCV+ compared to non-HCC
HCV+ and control groups. We found higher signals for miR-122 and miR-152 in non
tumor liver and HCC tissues compared to control tissues. Hepatocellular carcinoma
etiology had no detectable influence on miR-122 expression, whereas miR-152 was
increased in HCV+ tissue samples. CONCLUSIONS: Detection of low values of
circulating miR-152 is a potentially interesting marker of hepatocarcinogenesis
in HCV+ patients, in contrast to miR-122, which varies according to hepatocyte
damage.
PMID- 28512858
TI - Comprehension of handwriting development: Pen-grip kinetics in handwriting tasks
and its relation to fine motor skills among school-age children.
AB - BACKGROUND/AIM: Numerous tools have been developed to evaluate handwriting
performances by analysing written products. However, few studies have directly
investigated kinetic performances of digits when holding a pen. This study thus
attempts to investigate pen-grip kinetics during writing tasks of school-age
children and explore the relationship between the kinetic factors and fine motor
skills. METHODS: This study recruited 181 children aged from 5 to 12 years old
and investigated the effects of age on handwriting kinetics and the relationship
between these and fine motor skills. The forces applied from the digits and pen
tip were measured during writing tasks via a force acquisition pen, and the
children's fine motor performances were also evaluated. RESULTS: The results
indicate that peak force and average force might not be direct indicators of
handwriting performance for normally developing children at this age. Younger
children showed larger force variation and lower adjustment frequency during
writing, which might indicate they had poorer force control than the older
children. Force control when handling a pen is significantly correlated with fine
motor performance, especially in relation to the manual dexterity.
CONCLUSIONS/SIGNIFICANCE OF THE STUDY: A novel system is proposed for analysing
school-age children's force control while handwriting. We observed the
development of force control in relation to pen grip among the children with
different ages in this study. The findings suggested that manipulation skill may
be crucial when children are establishing their handwriting capabilities.
PMID- 28512859
TI - Exploring daily affective changes in university students with a mindful positive
reappraisal intervention: A daily diary randomized controlled trial.
AB - Brief and cost-effective interventions focused on emotion regulation techniques
can buffer against stress and foster positive functioning. Mindfulness and
positive reappraisal are two techniques that can mutually enhance one another to
promote well-being. However, research testing the effectiveness of interventions
combining mindfulness and reappraisal is lacking. The current pilot examined the
effect of a combined mindful-reappraisal intervention on daily affect in a 5-day
diary study with 106 university students. Participants were randomized to a
mindful-reappraisal intervention (n = 36), a reappraisal-only intervention (n =
34), or an active control activity (n = 36). All participants described a
negative event each day but only reappraised the event in the intervention
conditions. Using multilevel growth modelling, results indicated that negative
affect in both interventions declined over 5 days compared to the control;
however, there were no differences in the growth of positive affect. Compared to
reappraisal-only, the mindful-reappraisal group reported overall lower daily
negative affect and marginally higher daily positive affect over the 5-day
intervention. These findings suggest that brief daily practice combining
mindfulness and positive reappraisal can be trained as a self-regulatory resource
to promote positive affect and buffer negative affect above and beyond
reappraisal practice alone.
PMID- 28512860
TI - Intrinsic cellular and molecular properties of in vivo hippocampal synaptic
plasticity are altered in the absence of key synaptic matrix molecules.
AB - Hippocampal synaptic plasticity comprises a key cellular mechanism for
information storage. In the hippocampus, both long-term potentiation (LTP) and
long-term depression (LTD) are triggered by synaptic Ca2+ -elevations that are
typically mediated by the opening of voltage-gated cation channels, such as N
methyl-d-aspartate receptors (NMDAR), in the postsynaptic density. The integrity
of the post-synaptic density is ensured by the extracellular matrix (ECM). Here,
we explored whether synaptic plasticity is affected in adult behaving mice that
lack the ECM proteins brevican, neurocan, tenascin-C, and tenascin-R (KO). We
observed that the profiles of synaptic potentiation and depression in the dentate
gyrus (DG) were profoundly altered compared to plasticity profiles in wild-type
littermates (WT). Specifically, synaptic depression was amplified in a frequency
dependent manner and although late-LTP (>24 hr) was expressed following strong
afferent tetanization, the early component of LTP (<75 min post-tetanization) was
absent. LTP (>4 hr) elicited by weaker tetanization was equivalent in WT and KO
animals. Furthermore, this latter form of LTP was NMDAR-dependent in WT but not
KO mice. Scrutiny of DG receptor expression revealed significantly lower levels
of both the GluN2A and GluN2B subunits of the N-methyl-d-aspartate receptor, of
the metabotropic glutamate receptor, mGlu5 and of the L-type calcium channel, Cav
1.3 in KO compared to WT animals. Homer 1a and of the P/Q-type calcium channel,
Cav 1.2 were unchanged in KO mice. Taken together, findings suggest that in mice
that lack multiple ECM proteins, synaptic plasticity is intact, but is
fundamentally different.
PMID- 28512861
TI - Rapid diagnosis of sepsis with TaqMan-Based multiplex real-time PCR.
AB - BACKGROUND: The survival rate of septic patients mainly depends on a rapid and
reliable diagnosis. A rapid, broad range, specific and sensitive quantitative
diagnostic test is the urgent need. Thus, we developed a TaqMan-Based Multiplex
real-time PCR assays to identify bloodstream pathogens within a few hours.
METHODS: Primers and TaqMan probes were designed to be complementary to conserved
regions in the 16S rDNA gene of different kinds of bacteria. To evaluate
accurately, sensitively, and specifically, the known bacteria samples (Standard
strains, whole blood samples) are determined by TaqMan-Based Multiplex real-time
PCR. In addition, 30 blood samples taken from patients with clinical symptoms of
sepsis were tested by TaqMan-Based Multiplex real-time PCR and blood culture.
RESULTS: The mean frequency of positive for Multiplex real-time PCR was 96% at a
concentration of 100 CFU/mL, and it was 100% at a concentration greater than 1000
CFU/mL. All the known blood samples and Standard strains were detected positively
by TaqMan-Based Multiplex PCR, no PCR products were detected when DNAs from other
bacterium were used in the multiplex assay. Among the 30 patients with clinical
symptoms of sepsis, 18 patients were confirmed positive by Multiplex real-time
PCR and seven patients were confirmed positive by blood culture. CONCLUSION:
TaqMan-Based Multiplex real-time PCR assay with highly sensitivity, specificity
and broad detection range, is a rapid and accurate method in the detection of
bacterial pathogens of sepsis and should have a promising usage in the diagnosis
of sepsis.
PMID- 28512862
TI - Group-based parent training programmes for improving emotional and behavioural
adjustment in children.
PMID- 28512864
TI - Fish kairomones induce spine elongation and reduce predation in marine crab
larvae.
AB - Specialized defense strategies are induced in zooplankton upon detection of
predator chemical cues or kairomones. These defenses are well-described for
freshwater zooplankters, with morphological defenses being particularly striking,
but few studies have reported kairomone-induced morphological defenses in marine
zooplankton. Here, we compare morphological responses to kairomones in the larvae
of two marine crab species, estuarine mud crabs (Rhithropanopeus harrisii) and
Asian shore crabs (Hemigrapsus sanguineus). When reared in the presence of fish
kairomones, spine length increased by 2-3% in larval R. harrisii, while no
morphological changes were identified in H. sanguineus. In subsequent feeding
assays with a co-occurring fish predator (Atlantic silversides, Menidia menidia),
consumption of R. harrisii was lower on larvae that had been reared with
kairomones. In addition, we found that broods with smaller larvae are more likely
to exhibit increases in spine length after kairomone exposure. Hence, the
observed morphological response is likely influenced by larval size.
PMID- 28512863
TI - Defining a multimodal signature of remote sports concussions.
AB - Sports-related concussions lead to persistent anomalies of the brain structure
and function that interact with the effects of normal ageing. Although post
mortem investigations have proposed a bio-signature of remote concussions, there
is still no clear in vivo signature. In the current study, we characterized white
matter integrity in retired athletes with a history of remote concussions by
conducting a full-brain, diffusion-based connectivity analysis. Next, we combined
MRI diffusion markers with MR spectroscopic, MRI volumetric, neurobehavioral and
genetic markers to identify a multidimensional in vivo signature of remote
concussions. Machine learning classifiers trained to detect remote concussions
using this signature achieved detection accuracies up to 90% (sensitivity: 93%,
specificity: 87%). These automated classifiers identified white matter integrity
as the hallmark of remote concussions and could provide, following further
validation, a preliminary unbiased detection tool to help medical and legal
experts rule out concussion history in patients presenting or complaining about
late-life abnormal cognitive decline.
PMID- 28512866
TI - Medial sural artery perforator free flap for the reconstruction of leg, foot and
ankle defect: an excellent option.
AB - BACKGROUND: The defects over the leg, foot and ankle are best covered with a thin
pliable flap. The use of muscle flap for the reconstruction of these defects
leaves a grafted, aesthetically inferior result. The medial sural artery
perforator (MSAP) free flap gives a thin pliable tissue for the reconstruction
with better aesthesis. METHODS: The study design was retrospective case analysis
over a period of 2 years. All the patients who underwent flap for leg, foot and
ankle defect reconstruction in the form of MSAP free flap were included in the
study. The flap characteristics and aesthesis were assessed along with the
patient satisfaction. The flap complication and donor site morbidity were also
analysed. RESULTS: A total of seven MSAP free flaps were done for leg, foot and
ankle reconstruction. The mean flap size was 14.29 * 6.6 cm and mean pedicle
length was 9.71 cm. One flap had venous congestion post-operatively resulting in
marginal flap loss. All the flaps had acceptable aesthesis with good patient
satisfaction. There was donor site morbidity in two patients, in the form of
wound dehiscence. CONCLUSION: MSAP free flap is a reliable choice for leg, foot
and ankle defect reconstruction.
PMID- 28512865
TI - Efficacy and safety of ruxolitinib in intermediate-1 IPSS risk myelofibrosis
patients: Results from an independent study.
AB - Patients with myelofibrosis at intermediate-1 risk according to the International
Prognostic Score System are projected to a relatively long survival; nonetheless,
they may carry significant splenomegaly and/or systemic constitutional symptoms
that hamper quality of life and require treatment. Since registrative COMFORT
studies included only patients at intermediate-2/high International Prognostic
Score System risk, safety and efficacy data in intermediate-1 patients are
limited. We report on 70 intermediate-1 patients treated with ruxolitinib
according to standard clinical practice that were evaluated for response using
the 2013 IWG-MRT criteria. At 6 months, rates of spleen and symptoms response
were 54.7% and 80% in 64 and 65 evaluable patients, respectively. At 3 months,
ruxolitinib-induced grade 3 anemia and thrombocytopenia occurred in 40.6% and
2.9% of evaluable patients, respectively. Notably, 11 (15.9%) patients
experienced at least one infectious event >=grade 2. Most (82.6%) patients were
still on therapy after a median follow-up of 27 months. These data support the
need for standardized guidelines that may guide the decision to initiate
ruxolitinib therapy in this risk category, balancing benefit expectations and
potential adverse effects.
PMID- 28512868
TI - Metastasis-associated microRNA expression in canine uveal melanoma.
AB - BACKGROUND: Uveal melanoma (UM) is the most common primary intraocular tumour in
dogs. There is no effective means of predicting whether a tumour will
metastasize. microRNA (miRNA) metastasis signatures have been identified for
several human cancers, including UM. AIMS: In this study we investigated whether
metastasizing and non-metastasizing canine UMs can be distinguished by miRNA
expression levels. MATERIALS AND METHODS: miRNA microarray profiling was used to
compare miRNA expression in 8 metastasizing and 12 non-metastasizing formalin
fixed, paraffin-embedded (FFPE) primary UM biopsies. RESULTS: Fourteen miRNAs
exhibited statistically significant differences in expression between the
metastasizing and non-metastasizing tumours. Class prediction analysis pinpointed
9 miRNAs which categorized tumours as metastasizing or non-metastasizing with an
accuracy of 89%. Of the discriminating miRNAs, 8 were up-regulated in
metastasizing UM, and included 3 miRNAs implicated as potential "metastasis
activators" in human cutaneous melanoma. The expression of 4 of the miRNAs was
subsequently measured using the quantitative reverse transcription polymerase
chain reaction (RT-qPCR), and their up-regulation in metastasizing tumours
validated. CONCLUSION: miRNA expression profiles may potentially be used to
identify UMs that will metastasize, and miRNAs that are up-regulated in
metastasizing tumours may be targets for therapeutic intervention.
PMID- 28512867
TI - The structural basis for inhibition of the classical and lectin complement
pathways by S. aureus extracellular adherence protein.
AB - The extracellular adherence protein (Eap) plays a crucial role in pathogenesis
and survival of Staphylococcus aureus by inhibiting the classical and lectin
pathways of complement. We have previously shown that Eap binds with nanomolar
affinity to complement C4b and disrupts the initial interaction between C4b and
C2, thereby inhibiting formation of the classical and lectin pathway C3 pro
convertase. Although an underlying mechanism has been identified, the structural
basis for Eap binding to C4b is poorly understood. Here, we show that Eap domains
3 and 4 each contain a low-affinity, but saturable binding site for C4b. Taking
advantage of the high lysine content of Eap, we used a zero-length crosslinking
approach to map the Eap binding site to both the alpha'- and gamma-chains of C4b.
We also probed the C4b/Eap interface through a chemical footprinting approach
involving lysine modification, proteolytic digestion, and mass spectrometry. This
identified seven lysines in Eap that undergo changes in solvent exposure upon C4b
binding. We found that simultaneous mutation of these lysines to either alanine
or glutamate diminished C4b binding and complement inhibition by Eap. Together,
our results provide insight into Eap recognition of C4b, and suggest that the
repeating domains that comprise Eap are capable of multiple ligand-binding modes.
PMID- 28512870
TI - School-based physical activity programs for promoting physical activity and
fitness in children and adolescents aged 6 to 18.
PMID- 28512869
TI - Patterns of head and neck sarcoma in Australia.
AB - BACKGROUND: Sarcomas affecting the head and neck often require complex management
due to the combination of anatomic, aesthetic and oncological considerations. The
incidence and patterns of presentation are poorly understood and have not been
reviewed in the Australian population. METHOD: This study sourced incidence and
demographic data from the National Cancer Registry at the Australian Institute of
Health and Welfare for the years 1982-2009 (corresponding to 97.3% of the
Australian population). All cases of sarcoma, according to ICD-O-3 classification
((International Classification of Diseases for Oncology, 3rd edition), were
assessed. RESULTS: A total of 3911 new cases of sarcoma affecting the head and
neck were recorded during the period 1982-2009, including 1383, 2106 and 442
cases arising from skin, soft tissue and bone, respectively. The annual incidence
rate of sarcomas affecting the head and neck was 1.59 per 100 000 population. The
incidence of head and neck sarcoma rose substantially in older age groups (age 65
years and above) and was most common in male patients (69%). Malignant fibrous
histiocytoma (MFH) was the most common pathology. There was an increase in
incidence in skin-origin sarcoma in the head and neck, particularly affecting
elderly males. CONCLUSION: The incidence of head and neck sarcoma in Australia is
higher than that reported for an equivalent European population. The increase in
MFH arising from the skin in elderly male patients mirrors the patterns of common
cutaneous malignancy, particularly melanoma, suggesting that ultraviolet
radiation is an epidemiological factor. Management of head and neck sarcoma is
complex and best managed in a specialist multidisciplinary environment.
PMID- 28512871
TI - Sci-Fri PM: Planning-08: Zero diffusion radiochromic genipin-gelatin dosimeter.
AB - PURPOSE: To develop a zero diffusion radiochromic hydrogel by cross-linking
gelatin polymers with genipin, for three-dimensional (3-D) radiation dosimetry.
METHOD AND MATERIALS: Gelatin and genipin were dissolved in distilled water and
continuously stirred at 40C for thee hours and then sulfuric acid was acid prior
to placing gel in containers. Concentrations of genipin, gelatin and sulfuric
acid were varied to determine the optimal gel sensitivity for optical computed
tomography (CT). Photon beams (4 MV x-rays, 1*1, 2*2, 3*3 cm) irradiated a 10 cm
diameter cylinder of gel. Using a cone beam optical CT scanner at lambda = 590
nm, zero diffusion was observed by recording sequential 3D scans separated by 18
hours. Additional evidence was provided by sequential transmission photographs of
a cuvette containing a sample that had been exposed to a 0.8 mm diameter, 1 mW,
594 nm, He-Ne laser beam and photobleached. RESULTS: Radiochromic bleaching is a
fast process, complete within seconds of termination of irradiation. Dose
sensitivity increases with cross- linking density and sulfuric acid
concentration. The initial optical density limits dose sensitivity, requiring
approximately 30 Gy for 10 cm diameter samples to have reasonable contrast. More
sensitive but darker gels require smaller samples. A comparison of profiles
through 3D reconstructed dose distribution showed identical profiles for a time
interval of 18 hours. Visually the sample maintained this image for six months
when stored at 4C in a dark refrigerator. Transmission photographs of the laser
beam image recorded by photobleaching remained constant when stored a 23 C in the
dark for ten months. CONCLUSION: Radiochromic genipin gelatin gels form a
permanent and stable image when protected from bright visible light. This result
is a new, non-toxic material for 3D dosimetry.
PMID- 28512872
TI - Sci-Sat AM(1): Imaging-07: Open field normalization: How to avoid inflation to
MTF and DQE values caused by zero-frequency normalization.
AB - PURPOSE: To show that the novel open-field normalization technique prevents a
common error in calculation of the detective quantum efficiency (DQE) caused by
zero-frequency normalization of the modulation transfer function (MTF). METHOD
AND MATERIALS: Models describing zero-frequency and open-field normalization were
used to derive the resulting measured MTF, noise power spectrum (NPS) and DQE
using a finite region of interest (ROI) of image data. Simulated one-dimensional
images containing Gaussian blur were used to model a deterministic system and to
calculate the resultant values. Measurements were made using both zero-frequency
and open-field normalization with ROIs ranging in size from 1-10 cm. RESULTS: Use
of a finite ROI results in truncation of the system line-spread function (LSF)
causing the zero-frequency value of the measured MTF to be less than the true MTF
value of unity, and causes spectral leakage in both the MTF and NPS. Zero
frequency normalization of the MTF inflates values at all non-zero frequencies.
Since no zero-frequency normalization is performed on the NPS, this causes
inflated DQE values. Simulated results show a 6% inflation of DQE values for a
ROI of 10 cm, which increases as the ROI is reduced. Open-field normalization
accurately determines MTF and NPS (and thus DQE) values at all frequencies away
from zero frequency. CONCLUSION: Open-field normalization measurements provide a
good estimate of the true MTF and DQE. This approach should be used to avoid a
common error in DQE calculations that is not obvious and inflates DQE
calculations by 5-20%.
PMID- 28512873
TI - Poster - Thurs Eve-43: Verification of dose calculation with tissue inhomogeneity
using MapCHECK.
AB - MapCHECK (Sun Nuclear, Melbourne, FL) with 445 diode detectors has been used
widely for routine IMRT quality assurance (QA)1 . However, routine IMRT QA has
not included the verification of inhomogeneity effects. The objective of this
study is to use MapCHECK and a phantom to verify dose calculation and IMRT
delivery with tissue inhomogeneity. A phantom with tissue inhomogeneities was
placed on top of MapCHECK to measure the planar dose for an anterior beam with
photon energy 6 MV or 18 MV. The phantom was composed of a 3.5 cm thick block of
lung equivalent material and solid water arranged side by side with a 0.5 cm slab
of solid water on the top of the phantom. The phantom setup including MapCHECK
was CT scanned and imported into Pinnacle 8.0d for dose calculation. Absolute
dose distributions were compared with gamma criteria 3% for dose difference and 3
mm for distance-to-agreement. The results are in good agreement between the
measured and calculated planar dose with 88% pass rate based on the gamma
analysis. The major dose difference was at the lung-water interface. Further
investigation will be performed on a custom designed inhomogeneity phantom with
inserts of varying densities and effective depth to create various dose gradients
at the interface for dose calculation and delivery verification. In conclusion, a
phantom with tissue inhomogeneities can be used with MapCHECK for verification of
dose calculation and delivery with tissue inhomogeneity.
PMID- 28512874
TI - Sci-Fri PM: Planning-01: Measured electron and x-ray angular distribution data
for benchmarking Monte Carlo codes.
AB - Monte Carlo (MC) studies of the output of medical linear accelerators have
demonstrated that in-air profiles are useful in the beam commissioning process. A
recent investigation of x-ray profiles (Tonkopi et al, Med. Phys 32 (9), 2005)
showed very good agreement between measurement and EGSnrc calculations but to
achieve this level of agreement the beam linac spot size, energy and angular
divergence had to be treated as variables. In this project we carried out
measurements and MC calculations for an electron accelerator for which the
initial beam parameters are well known. Two sets of investigations were carried
out. In the first we measured electron scatter distributions for a range of
scattering foils and electron energies of 13 and 20 MeV. The profiles were
parameterised and compared to EGSnrc Monte Carlo calculations. It was found that
generally the EGSnrc calculations gave agreement with the measurements within 1.5
%. In the second investigation, which is on-going, in-air profiles were obtained
for photon beams produced using different targets (from beryllium to lead).
Measured angular distributions were obtained using ion chambers with different
build-up caps (low and high-Z) and the sensitivity of the data to small changes
in geometry (e.g., moving the x-ray target) was investigated. The photon energy
fluence was calculated using EGSnrc and preliminary indications are that the
measured and calculated distributions agree to better than 5 %. Work supported in
part by NIH grant R01 CA104777-01A2.
PMID- 28512875
TI - Sci-Fri PM: Planning-12: Class II division interpretation of the amended Class II
regulations.
AB - The proposed amendments to the Class II regulations are expected to come into
effect in May 2008. This presentation will provide highlights of the change to
Class II regulations and how those changes will be interpreted by the CNSC during
licence assessments and inspections. The changes to the regulations are designed
to correct a number of regulatory deficiencies that have come to light since the
regulations came into force.
PMID- 28512876
TI - Sci-Sat AM(2): Brachy-03: Monte Carlo dosimetry for I-125 and Pd-103 eye plaque
brachytherapy.
AB - A Monte Carlo study of dosimetry for eye plaque brachytherapy was performed.
BrachyDose, an EGSnrc user-code which makes use of Yegin's multi-geometry
package, was used to fully model Iodine-125 (model 6711) and Palladium-103 (model
200) brachytherapy seeds and the standardized plaques of the Collaborative Ocular
Melanoma Study (COMS). Three-dimensional dose distributions in the eye region
were obtained. In general, dose to water was scored, however the implications of
replacing water with eye materials was explored. The effect of the gold alloy
(Modulay) backing was investigated and the dose was found to be sensitive to the
elemental composition of the backing. The presence of the silicon polymer
(Silastic) seed carrier resulted in substantial dose decreases relative to water,
particularly for Pd-103. For the Modulay backing and Silastic insert combination
in a 20 mm plaque, the dose decrease relative to water is of the order of 12% for
I-125 and 20% for Pd-103 at a distance of 1 cm from the central seed along the
plaque's central axis. For the configurations of seeds used in COMS plaques,
interseed attenuation is a small effect within the eye region. The introduction
of an air interface results in a dose reduction in its vicinity which depends on
the plaque's position within the eye and the source type. The dose distributions
in the eye for the two different sources were compared and, for the same
prescription dose, Pd-103 generally offers a lower dose to critical normal
structures.
PMID- 28512878
TI - Sci-Sat AM(2): Brachy-09: Investigation of catheter displacement in HDR prostate
brachytherapy.
AB - During prostate cancer treatment with HDR brachytherapy, catheters are inserted
into the prostate. Between planning and treatment, catheters may move inferiorly
due to edema. If undetected, treatment proceeds without correcting the catheter
displacement, and an incorrect treatment is delivered. The purpose of this study
was to investigate the consequences of catheter displacement on prostate coverage
and critical structure avoidance. Ten patient plans were selected in which
movement of the catheters had been observed. The original treatment plan,
generated using Nucletron PLATO (ver. 14.3.2), was adjusted introducing inferior
catheter offsets of 5, 10, 20, and 30 mm. The original treatment dwell times were
re-entered into the offset plans to determine the consequences of the
displacement. DVH data was calculated for the prostate, rectum, urethra, and
bladder. Prostate V100 decreased from 99% to 36% over the ten patients studied.
For the urethra, the D10 increased (114.1% to 128.2%), as did the V125 (2.7% to
12.8%). In the rectum the V75 initially increased as the catheters shifted
inferiorly, but dropped as the shift increased beyond 10 mm. In the penile bulb
the V75 increased as a function of shift (from 2.1% to 44.8%). Every effort
should be made to ensure that the catheters do not move during prostate
treatment. A small shift, 5 mm, would result in a small deviation of the dose
distribution. In this case a re-optimization of the plan is unnecessary. Larger
shifts will have a serious impact on the dose delivered to the prostate and to
sensitive normal structures.
PMID- 28512877
TI - Sci-Fri AM: YIS-04: Scatter correction of cone beam optical computed tomography
for polymer gel dosimetry.
AB - Optical computed tomography (OptCT) may become the preferred scanning method for
gel dosimetry dose validations, due to its high sensitivity and relatively low
cost. Cone beam computed tomography (CBCT) arrangements are advantageous because
of reduced scan time. However, CBCT arrangements are more sensitive to errors
associated with scatter than other CT configurations. Unfortunately in polymer
gel dosimetry this problem is amplified as the primary mode of beam attenuation
is through scatter. Thus, managing and reducing the effects of scatter remains an
important challenge for cone beam OptCT. In this work we examine two schemes for
reducing the effects of scatter in the Vista cone beam OptCT system. First, we
employed a pair of anti-scatter polarizing planes to reduce the magnitude of
stray light reaching the camera. Secondly, we implemented a beam stop array (BSA)
sampling method -which has been successful in correcting for scatter in X-ray
CBCT- to obtain scatter field measurements that are subtracted from CT
projections removing veiling glare. While both implementations reduced scatter
related artifacts, the BSA technique yielded greater improvement without obvious
image degradation. Comparative studies between absorbing dye standards and
colloidal scattering standards with the same spectrophotometric optical
attenuation revealed that application of the BSA technique nullified OptCT
measurement disagreements between scattering and absorbing systems. When the BSA
scatter correction technique was applied to polymer gel dosimetry 3%3mm agreement
rose from 79.2% to 99.82%. These findings underscore the strength of the BSA
sampling technique and its utility in cone beam OptCT.
PMID- 28512879
TI - Sci-Fri PM: Planning-05: Saving trees and improving workflow.
AB - Patient treatment preparation is a multi-step process requiring inputs from a
range of disciplines and technologies. Our centre generates just over 4500
treatment plans annually and operates from two main campuses. A large, split
program presents unique challenges during treatment preparation and has provided
the impetus for a completely electronic treatment process. Throughout 2006 and
2007, we migrated our external beam treatment planning to the Computerized
Medical Systems (CMS) product line. Utilizing a thin-client architecture, CMS
supports distributed (multi-site) planning. Coincident with the treatment
planning upgrade, IMPAC Multi-Access was configured to provide a paperless and
filmless treatment record and electronic patient workflow. Standardized treatment
objectives were also implemented in the form of site-group approved care plans.
Details of the pretreatment process and the CMS / IMPAC implementation will be
presented as well as a workflow time analysis. To date, treatment preparation
times have been reduced by 25% (2.5 days) as a result of workflow improvements,
representing a clear benefit to both staff and patients.
PMID- 28512880
TI - Sci-Sat AM(1): Imaging-04: Respiratory errors in cardiac PET/CT with manual
alignment of the CT image.
AB - Respiratory motion can produce misregistration errors between CT and PET images
in cardiac PET/CT imaging. The objective of this study was to determine if manual
registration of a single-phase end-expiration CT scan to the PET image would
eliminate respiratory-induced artifacts. Listmode data from 71 cardiac PET
patient scans were rebinned into a 8-frame respiratory-gated image series based
on a respiratory trigger signal obtained with an optical tracking system. CT
based attenuation correction (AC) was performed after registering the CT image
with the mean position of the PET images. The 8 phases of the gated PET study
were coregistered and the breathing motion was measured. Images from end
inspiration and end-expiration were compared to assess the effect of motion.
Studies in which the motion was >8mm were reconstructed again, with the CT scan
aligned to end-expiration or end-inspiration, to determine if phase-specific
registration could reduce the residual errors. The motion was found to be
greatest in the axial direction (mean 4.1mm +?- 1.8mm) and 4 Rb stress studies
(17%) had motion >8mm. The maximum displacement during breathing was greater for
Rb-stress imaging (<15mm) than for resting (<7.5mm) or NH3-stress (<5.4mm)
imaging. No significant differences were noted between the respiratory phases of
the rest studies. Errors in myocardial radiotracer uptake of up to 35% were noted
between end-inspiration and end-expiration for studies with >8mm of motion. Phase
specific registration of the CT reduced the extent of the errors but did not
fully resolve them, suggesting that more sophisticated AC is required.
PMID- 28512881
TI - Poster - Thurs Eve-40: The potential of using SPECT ventilation information with
IMRT for functional lung avoidance in radiotherapy of non small cell lung cancer.
AB - We have investigated the feasibility of using ventilation scans obtained from
single photon emission computed tomography (SPECT) in intensity-modulated
radiation therapy (IMRT) planning in lung cancer radiotherapy to avoid well
functioning lung. We fused SPECT ventilation scans acquired at GE Hawkeye SPECT
CT of ten stage-III lung radiotherapy patients with planning CT in treatment
planning system (Pinnacle v8.0, Philips Medical Systems). We automatically
segment out 50% and 70% ventilated volumes. For each patient, we generated IMRT
plans using nine equally spaced beams with and without avoiding well ventilated
volume. They were compared with three beam IMRT plans with beam directions chosen
to minimize the mean dose to the ventilated lung volumes, while keeping cord dose
below tolerance and dose uniformity in the target. The plans generated using
functional lung avoidance information reduces the doses to the functioning lung.
With both IMRT avoidance plans, we could not obtain better functional avoidance
or lower V-20Gy (volume receiving 20Gy or more) for total lung when the planning
target volume (PTV) was surrounded by functional lung volumes. We were able to
achieve better ventilated lung avoidance and lower total lung V-20Gy when the PTV
is close to, but not surrounded by functioning lung volumes. For patients with
the PTV that is far from 50% and 70% functional lung volumes, three-field IMRT
spare the ventilated lung as well as nine-field IMRT ventilation avoidance plan,
with a lower total lung V20-Gy.
PMID- 28512882
TI - Sci-Sat AM(2): Brachy-07: Tomosynthesis-based seed reconstruction in LDR prostate
brachytherapy: A clinical study.
AB - To develop a tomosynthesis-based dose assessment procedure that can be performed
after an I-125 prostate seed implantation, while the patient is still under
anaesthesia on the treatment table. Our seed detection procedure involves the
reconstruction of a volume of interest based on the backprojection of 7 seed-only
binary images acquired over an angle of 60 degrees with an isocentric imaging
system. A binary seed-only volume is generated by a simple thresholding of the
volume of interest. Seeds positions are extracted from this volume with a 3D
connected component analysis and a statistical classifier that determines the
number of seeds in each cluster of connected voxels. A graphical user interface
(GUI) allows to visualize the result and to introduce corrections, if needed. A
phantom and a clinical study (24 patients) were carried out to validate the
technique. A phantom study demonstrated a very good localization accuracy of
(0.4+/-0.4) mm when compared to CT-based reconstruction. This leads to dosimetric
error on D90 and V100 of respectively 0.5% and 0.1%. In a patient study with an
average of 56 seeds per implant, the automatic tomosynthesis-based reconstruction
yields a detection rate of 96% of the seeds and less than 1.5% of false
positives. With the help of the GUI, the user can achieve a 100% detection rate
in an average of 3 minutes. This technique would allow to identify possible
underdosage and to correct it by potentially reimplanting additional seeds. A
more uniform dose coverage could then be achieved in LDR prostate brachytherapy.
PMID- 28512883
TI - Sci-Sat AM(1): Imaging-06: Proximity-based modification to an automatic method
for tumor delineation using MRSI.
AB - Quantifying the relative levels of Choline (Cho) to N-Acetylaspartate (NAA) has
been the method of choice by many groups as a mean to biologically identify
tumors in the brain. Mcknight et al. have introduced an automatic technique for
delineating tumors biologically using MRSI. A statistical model is used to
separate tumors from normal tissue based on the relative concentrations of
Choline and NAA in both tissue types; that method is commonly referred to as the
Choline-to-NAA Index (CNI). In their work, it is assumed that the variation in
the relative levels of Cho to NAA in normal brain is unnoticeable to within 2
standard deviations of the mean. However, developments in MRSI sequences have
enabled the detectablity of more variations within the relative levels of Cho to
NAA in normal tissue. With the uncertainty in the Cho to NAA levels of normal
tissue increasing, it is essential to modify the CNI method to improve its
specificity. This work introduces a modification to the CNI method developed by
McKnight et al. that would address such increase in uncertainty. Instead of
relying on an arbitrary CNI value of 2 to define the tumor boundaries, our method
defines a high certainty tumor volume, surrounded by a region of uncertainty.
Then based on their proximity to high certainty tumor regions, the voxels in the
uncertainty region are segmented to either tumor or normal tissue. Preliminary
results suggest that the proposed modified method decreases the number of false
positive resulting from the original CNI method.
PMID- 28512884
TI - Poster - Thurs Eve-42: A revision of the gamma-evaluation: Initial interpretation
of dose disagreements on gamma-vector fields.
AB - Gamma evaluations are a common clinical tool used as a quantitative comparison
between dose-distributions, combining both dose difference and distance to
agreement criteria. Because gamma evaluations permit rapid analysis of agreement
between complex dose distributions, they are often a preferred comparison method
for assessing delivery of conformal radiotherapy distributions. Although the
comparison provides a useful measure of agreement between distributions when the
index is less than one, the scalar gamma value provides little information into
the clinical significance or source of disagreements of failing gamma values
(i.e., when gamma>1). Previously, Stock et al., have presented the gamma angle as
an indicator of the relative influence of the distance to agreement versus the
dose difference on gamma. We present a modification to the gamma evaluation such
that the complete 3D gamma vector information is considered. The predictive
nature of each vector component was investigated by simulating various dose
disagreements in test distributions. Misalignment tests revealed that the mean
gamma vector components indicate the offset direction and relative magnitude for
all test distributions. The mean dose component of the gamma vector was
prognostic of double Gaussian overdoses and underdoses in a virtual conformal
delivery. The response of the vector field depends on properties distinctive to
each distribution, such as the local dose gradient. Understanding how these
unique properties affect the vector field may permit better diagnosis of dose
disagreement sources. Other vector field properties, such as curl and divergence,
may yet provide more information for interpreting the cause and significance of
gamma>1.
PMID- 28512885
TI - Sci-Fri AM: YIS-10: Development of a flat panel detector with avalanche gain for
low-dose x-ray imaging.
AB - Digital flat panel detectors are increasingly being used in radiography and
fluoroscopy. The imaging performance of current systems, however, is compromised
by electronic noise at the low X-ray exposures employed in fluoroscopy and low
dose radiography. In other words, current flat panel detectors are not quantum
noise limited at these low radiation exposures. There is thus a need to develop
an imaging detector with the high sensitivity of an X-ray image intensifier and
the inherent advantages of a solid-state flat panel detector. Towards this end,
we have developed and characterized a novel solid-state device capable of
providing very high avalanche gains and an excellent temporal response. The
device which is based on the amorphous photoconductor a-Se, is scalable (i.e. can
be manufactured in large areas), can overcome electronic noise even at the lowest
X-ray exposures used in diagnostic imaging (0.1 MUR/frame at the detector) and
has a very low level of dark current. Here, we investigate the gain and temporal
characteristics of this device and discuss its applicability for low exposure X
ray imaging as well as the effects of avalanche gain on the detective quantum
efficiency. Coupled to a high-resolution structured CsI X-ray scintillator and a
thin film transistor array, this device should provide a true solid-state
alternative to the X-ray image intensifier, which is both robust and cost
effective. This should open the door to dose-efficient flat panel imagers for
radiography and fluoroscopy as well as a number of other demanding medical
imaging applications.
PMID- 28512886
TI - Sci-Fri PM: Planning-11: Selection and optimization of angiographic roadmap
images for magnetic resonance guided catheter tracking.
AB - As endovascular magnetic resonance (MR) techniques for device tracking and
guidance move closer to demonstrating clinical feasibility, more investigation in
the generation and optimization of vascular roadmap images is need to achieve the
full benefit of MR-guided procedure. MR angiographic roadmap imaging requires
high signal-to-noise (SNR), good vascular-to-background contrast and short
acquisition time. These requirements not only qualify the appropriate roadmaps
for therapy, but also guide in the optimization of their acquisition parameters.
We hypothesize that among the well established MR angiographic techniques, low
resolution phase-contrast (PC) images would prove satisfactory for vascular
roadmap imaging. To verify this, four potential MR angiography techniques,
specifically, time-of-flight, contrast-enhanced, phase-contrast and black-blood
angiography, were explored for roadmap imaging using a canine model on a 3 T MR
scanner. PC angiography was specifically performed to evaluate impact of key
parameters on the SNR efficiency and vascular-to-background contrast efficiency
in order to optimize the sequence for therapeutic use. Data were collected from
five canines. Phase-contrast angiography was found to be most suitable for
generating vascular roadmap for MR-guided endovascular therapy. It was also found
that small acquisition matrix and large FOV produced satisfactory roadmap images
provided that the size of the vessel of interest was more than a few times the in
plane pixel dimension. Also, reducing the phase encoding steps had minimal effect
on vessel oriented parallel to the phase encode direction.
PMID- 28512887
TI - Sci-Sat AM(2): Brachy-02: Image guided brachytherapy (IGBT) for HDR prostate
treatment : Pre-treatment verification using cone beam imaging to determine
catheter displacement.
AB - PURPOSE: Prostate HDR brachytherapy utilizes flexible catheters for treatment
delivery. Catheters are inserted under US guidance and planning performed on CT
images. This study investigates the efficacy of performing kV cone beam imaging
prior to treatment to quantify catheter displacement and dose delivered.
MATERIALS AND METHODS: Twenty consecutive patients undergoing HDR prostate
brachytherapy were planned using CT images. Under US guidance, catheters and four
fiducial markers were placed into the prostate. Before treatment, visual check
confirmed no movement of the template sutured to the perineum and no movement
relative to the template. Cone beam imaging was performed using an isocentric
mobile c-arm. Catheters were re-adjusted if required by the Radiation Oncologist.
The cone beam images prior to adjustment were later fused with the planning CT.
RESULTS AND DISCUSSION: In 17 of the 20 patients, catheter displacements
exceeding 0.5cm were observed. Compared to the CT based plan, an average catheter
displacement of 1.0cm results in a decrease in the V100 of the prostate by
approximately 27%, urethra V120 increased by about 7%, and urethra D10 increased
by about 4%. Approximately 65% of patients had average catheter displacements of
1.0cm and larger. Three patients had catheter shifts larger than 2cm.
CONCLUSIONS: Catheter movement within the patient can be significant and cone
beam imaging prior to treatment delivery provides precise imaging to determine
catheter displacement. Cone beam imaging time using an isocentric C-arm is
sufficiently short enough (~ 2 minutes) so as to make this a viable quality
assurance tool in the OR.
PMID- 28512888
TI - Sci-Fri AM: YIS-03: Simulated annealing optimization of the pre-target electron
beam in Monte Carlo virtual linac models.
AB - The purpose of this study is to develop a method for determining the initial
parameters of the pre-target electron beam within a Monte Carlo (MC) accelerator
model able to produce accurate 18 MV 40*40 cm2 photon field profiles. We have
developed a novel method by which the electron beam intensity distribution can be
reverse engineered to reproduce measured dose distributions. The method begins
from a cylindrically symmetric pre-target electron beam (radius 0.5 cm) of
uniform intensity. This beam is subdivided into annular regions of fluence for
which each region is individually transported through the accelerator head and
into a water phantom. A simulated annealing search is then performed to determine
the optimal combination of weights of the annular fluences that provide a best
match between measured dose distributions and the weighted sum of annular dose
distributions. Remarkably, the intensity distribution converges to a solution
that is predominantly Gaussian, with a FWHM=1.1mm. In addition, the solution
contains an important secondary "extra focal halo" on the order of 10% of the
maximum Gaussian intensity. Agreement of the 40*40 cm2 photon field profiles with
measurement was within 0.5%. The method greatly reduces the effort required to
commission a MC accelerator model for clinical use and has achieved better
agreement with measurement than other methods described in the literature. Our
derived value of the electron beam FWHM agrees with that measured by Jaffray et
al, 1993, and the "extra focal halo" is in qualitative agreement with their
measurements of extra focal radiation.
PMID- 28512889
TI - Sci-Sat AM(2): Brachy-08: Monte Carlo calculations of 192Ir high dose rate
brachytherapy treatment plans using CT and cone beam CT images.
AB - The feasibility of using cone beam computed tomography (CBCT) images for Monte
Carlo (MC) brachytherapy dose calculations has been investigated. To evaluate the
effects of tissue heterogeneities and finite patient dimensions for 192Ir high
dose rate treatment, CT-based MC calculations for breast and head and neck cases
were first performed using the PTRAN_CT photon transport code. PTRAN_CT is an
accelerated MC code specifically designed for patient-specific dose calculations.
Muscles and adipose tissues, which are nearly indistinguishable in CBCT images,
are found to cause minimal dose perturbations at 192Ir energies compared to
water. The proximity of the tumor to the skin, however, will have an observable
impact on the dose up to a few percent. Therefore, for CBCT calculations, a
reasonable assignment of material and density values to the patient voxel
geometry, with a good delineation of the skin and bony structures, will suffice
for MC dose calculations. A CBCT-based calculation for an actual treatment plan
with the tumor close to the cheek was performed. The results were compared to
TG43 calculations to quantify the dose differences in the target and critical
structures. Since the dose delivered to the tumor is mostly primary dose,
deviations are found mostly in the organs at risk where scatter contribution
becomes more significant. This study shows that for HDR brachytherapy
applications, CBCT-based MC calculations is a feasible option despite inferior
image quality and larger uncertainties in the Hounsfield Units compared to CT
images. Research supported by Nucletron BV.
PMID- 28512890
TI - Sci-Fri PM: Planning-04: Dose escalation study using anatomy-based aperture IMRT
and SPECT perfusion images for lung cancer.
AB - In the case of non-small cell lung cancer, doses typically prescribed (60-66 Gy)
are not sufficient to ensure a satisfactory tumor control probability. Dose
escalation needs to be realized, but dose to organs at risk (OARs) must be kept
under widely accepted clinical thresholds. Also, lung functionality is not
homogeneously distributed over all the volume: single-photon emission computed
tomography (SPECT) allows spatial characterization of perfusion, open the way to
the design of treatments plans that could preferentially avoid highly-functional
lung. In this study, three cases of lung cancer were retrospectively used to
assess the capacity of an anatomy-based aperture inverse planning system to
realize dose escalation while limiting dose to perfused lung. Plans were
generated for four-beam non-coplanar configurations, mixing 6 and 23 MV photon
beams. All dose calculations were performed using Pinnacle3
superposition/convolution algorithm. An increasing dose was prescribed to a
subvolume of the initial planning target volume. Levels of escalation achieved
for the three cases studied were 81 Gy, 111 Gy and 66 Gy to the subvolume.
Escalation was limited in two cases by the dose to the esophagus and in the other
case by the presence of overdosages near beam entry ports. Calculation of dose
volume parameters for OARs shows that they respect clinical thresholds. Plans
generated by the system are less complex than plans generated in beamlet-based
IMRT, because of the use of few, large segments. The approach used in this study
allows important dose escalation, potentially improving treatment outcome.
PMID- 28512891
TI - Sci-Sat AM(1): Imaging-03: On-line dynamic contrast enhanced cone-beam CT for
measuring.
AB - We propose a novel on-line functional imaging method with which tumor
microenvironment can be quantified at the treatment unit. It is an X-ray contrast
enhanced method based the (kv) cone beam CT (CBCT) platform and it promises to
provide a surrogate measurement of tumor perfusion. The method was tested with 6
rabbits implanted with VX2 tumor. The technique involves a baseline CBCT followed
by a contrast enhanced CBCT synchronized with contrast injection. The scan time
for each CBCT is approximately 2 minutes during which a set of projections are
acquired. The conventional reconstruction approach of contrast enhanced CBCT will
give a single volumetric image with no temporal signature. On the other hand, the
proposed technique makes use of a mathematical expression to parameterize the
wash-in and wash-out behavior of contrast uptake in each voxel. Based on the
projection data, the new method uses non-linear optimization to solve for the
parameters describing the dynamic characteristics of injected contrast with which
tumor perfusion can be derived. In our rabbit study, dynamic contrast enhanced
images were reconstructed with the CBCT projections by the proposed method.
Results show that the estimated contrast enhancement with the proposed CBCT
method is in excellent agreement with the measured enhancement by CT. The
proposed CBCT method is sensitive for detecting changes in the tumor
microenvironment as a result of radiation treatment.
PMID- 28512892
TI - Poster - Thurs Eve-39: Full 3D dose calculation for total body irradiation: A
comparison study between treatment planning systems in homogeneous and
heterogeneous conditions.
AB - PURPOSE: To perform full 3D heterogeneous dose calculations for total body
irradiation (TBI) cases and compare different treatment planning softwares (TPS).
METHOD: A retrospective study was performed on 7 patients. Dose distributions
obtained with Pinnacle3 v.7.9u (Philips Medical Systems) were compared with the
ones calculated using our actual TBI planning system Theraplan Plus (TPP) by MDS
Nordion/Nucletron. Two different Pinnacle3 models were studied: standard beam
commissioning (std_Pinnacle3 ) and TBI commissioning (TBI_Pinnacle3 ). For the
later case, commissioning was adapted for the special TBI conditions (extended
SSD of 190cm, large field, acrylic beam spoiler, and out of field dose (OFD)).
RESULTS: Significant differences are found between the TPP, std_Pinnacle3 and
TBI_Pinnacle3 dose distributions. For the relative mid-line doses, differences up
to 12% were observed. Systematic overestimations of 5% were found in patients
extremities between TPP and TBI_Pinnacle3 . Average dose underestimation of 3%
was observed between std_Pinnacle3 and TBI_Pinnacle3 . Differences in patient
extremities are attributed to the OFD contribution which is not correctly
computed in TPP and std_Pinnacle3 . Dose comparison outside the patient's mid
line showed greater differences (up to 20%) between models. Accurate 3D
heterogeneous dose calculations with TBI_Pinnacle3 model show major differences
(homogeneous versus heterogeneous) in high and low density regions. Dose
overestimation of 5% was observed in bony regions and dose underestimation of 5%
to 10% was observed in lung regions. CONCLUSION: Those results are of major
interest since they show a strong dependence of the dose calculation outcome on
both TPS and commissioning used, potentially leading to significant dose
misevaluation.
PMID- 28512893
TI - Sci-Sat AM(2): Brachy-06: A Comparison of MR/CT fusion versus CT alone for
assessment of implant quality in permanent prostate brachytherapy.
AB - Low dose-rate permanent implant brachytherapy is widely used in the management of
patients with early stage prostate cancer. An assessment of the implant quality
is usually carried out 30 days after the implant is delivered, using computed
tomography (CT) to identify the prostate and seeds. This is difficult due to poor
contrast of the prostate and the superposition of seeds in the CT images.
Magnetic resonance (MR) imaging offers superior contrast but inferior
visualization of seeds. At our centre, patients are imaged using both CT and T2
weighted MR 30 days after an implant, and the image sets are fused using a
commercial software package. The seeds are identified on CT and the prostate
volumes are contoured on MR, with fusion performed by matching seeds on CT with
seed signal voids on MR. The purpose of this study was to compare standard
prostate post-implant dosimetric parameters (D90, V100, etc.) for prostates
contoured on CT alone (MR blinded) versus MR/CT fusion. 25 patients were
evaluated with all contouring performed by the same physician. We found that the
prostate volume was overestimated using CT alone as compared to MR/CT fusion
(mean: 37.2cc vs. 35.0cc respectively, p = 0.033). We also found that dosimetric
parameters were underestimated for CT alone compared to MR/CT fusion, including
D90 (mean: 144.3Gy vs. 150.8Gy respectively, p = 0.005) and V100 (mean: 89.2% vs.
91.0% respectively, p = 0.01). Centres using CT alone for post-implant dosimetry
may therefore be underestimating their implant quality.
PMID- 28512894
TI - Sci-Fri AM: YIS-07: A new paradigm for improving IMRT: Selection of beam
orientations by optimizing beam intersection volume.
AB - A beam orientation optimization (BOO) algorithm based on optimizing beam
intersection volume (BIV) components within an Organ-at-Risk (OAR) is proposed to
improve conventional intensity-modulated radiation therapy (IMRT). A simulated
annealing algorithm was employed to search for the optimal set of five beam
orientations (5-opt) which simultaneously minimize the BIV components within an
OAR. The 5-opt plans were compared to standard 5, 7, and 9 equiangular-spaced
beam plans (5-equi, 7-equi, 9-equi) for: (1) gastric (2) Radiation Therapy
Oncology Group (RTOG) P-0126 prostate and (3) RTOG H-0022 oropharyngeal (Stage
III, IV) cancer patients. In the gastric case, the coplanar 5-opt plan reduced
the right kidney V 20 Gy by 41.1%, 32.1%, and 29.5% compared to the 5-equi, 7
equi, and 9-equi plans. In the prostate case, the coplanar 5-opt plan improved
rectal sparing over all standard plans with a reduction of the V 75 Gy, V 70 Gy,
V 65 Gy, and V 60 Gy of 3.9%, 6.2%, 8.1%, and 10.6% compared to the 5-equi plan.
In both oropharyngeal cases, the non-coplanar 5-opt plan substantially reduced
the V 30 Gy and mean dose to the contralateral parotid compared to the 5-equi, 7
equi, and 9-equi plans: (Stage-III) 8.9%, 7.0%, 8.6% and 4.1 Gy, 2.5 Gy, 2.7 Gy
(Stage-IV) 11.2%, 11.2%, 10.8% and 7.8 Gy, 7.9 Gy, 8.0 Gy. In conclusion, the
method of optimizing BIV to produce substantial improvements in OAR sparing over
conventional IMRT has been demonstrated to be robust for application to a variety
of IMRT treatment sites.
PMID- 28512895
TI - Poster - Thurs Eve-41: Imaging and radiation delivery in helical tomotherapy:
Phantom study of a moving target.
AB - Treating lung cancer with radiation therapy by guaranteed delivery of the
prescription dose to the target is difficult due to tumour motion. The standard
approach to account for motion effects consists of adding a substantial margin to
a lesion visible on the CT study. Larger irradiated volume results in increased
dose deposition in healthy lung and the potential for patient complications. This
investigation focuses on determining the optimal choice of planning CT mode for
improved radiation delivery in terms of better target coverage and sparing of
healthy organs. Dosimetric measurements were performed on a helical tomotherapy
unit. A Quasar(r) (Modus Medical Devices, London, ON) respiratory phantom was
imaged while a polystyrene target moved sinusoidally with a period of 4 s and
amplitude of 2 cm. For target moving in superior-inferior and lateral directions,
conventional fast-CT image studies were created, as well as maximum intensity
projection (MIP) and average intensity projection (AveIP) image studies using
four-dimensional CT information. All types of CT studies were used to develop
treatment plans with a prescription of 2 Gy per fraction to the target outlined
according to the imaged data. Measurements of dose deposition were made in four
locations within the moving target using an Exradin A1SL ion chamber. Comparing
all results to the dose measured at the centre of the static phantom, the MIP
plans overdose the target, the fast-CT results vary from case to case, while the
AveIP plans provide consistent dose distribution across the target within 2% of
the normalization dose.
PMID- 28512897
TI - Sci-Fri PM: Planning-10: The replacement correction factors for cylindrical
chambers in megavoltage beams.
AB - The replacement correction factor (Prepl ) in ion chamber dosimetry accounts for
the effects of the medium being replaced by the air cavity of the chamber. In TG
21, Prepl was conceptually separated into two components: fluence correction, Pfl
, and gradient correction, Pgr . In TG-51, for electron beams, the calibration is
at dref where Pgr is required for cylindrical chambers and Pfl is unknown and
assumed to be the same as that for a beam having the same mean electron energy at
dmax . For cylindrical chambers in high-energy photon beams, Prepl also
represents a major uncertainty in current dosimetry protocols. In this study,
Prepl is calculated with high precision (<0.1%) by the Monte Carlo method as the
ratio of the dose in a phantom to the dose scored in water-walled cylindrical
cavities of various radii (with the center of the cavity being the point of
measurement) in both high energy photon and electron beams. It is found that, for
electron beams, the mean electron energy at depth is a good beam quality
specifier for Pfl ; and TG-51's adoption of Pfl at dmax with the same mean
electron energy for use at dref is proven to be accurate. For Farmer chambers in
photon beams, there is essentially no beam quality dependence for Prepl values.
In a Co photon beam, the calculated Prepl is about 0.4-0.6% higher than the TG-21
value, indicating TG-21 (and TG-51) used incorrect values of Prepl for
cylindrical chambers.
PMID- 28512896
TI - Sci-Fri AM: YIS-09: The effect of magnetic interference on a coupled MR-linac
system: Optimization of 3D FEM linac model.
AB - PURPOSE: The coupling of a 0.2T bi-planar Magnetic Resonance Imager and medical
linear accelerator (linac) is proposed to provide real-time Image Guided
Radiotherapy. This coupling necessitates the linac to be within the fringe fields
of the bi-planar magnets causing magnetic interference. The design and
optimization of the minimum required shielding is necessary to reduce the fringe
field magnitudes to a point where a clinically useful radiation beam is produced.
METHOD: A first step to designing shielding is the full 3D radio-frequency
modeling of the linac waveguide using the Finite Element Method. Various
optimizations were performed on the linac model in order to achieve a desired
resonant frequency, pi/2 phase shift per cavity and other desired properties. An
accelerating cavity (AC) and coupling cavity (CC) was first optimized in 3D to
have identical resonant frequencies before the full 3D model was generated.
RESULTS: In order to increase the capture efficiency of the injected electrons,
the electric field in the first AC was reduced by shifting the first CC towards
the gun end of the linac. The input waveguide AC dimensions were adjusted to
account of the additional coupling iris and the last full AC had its gap length
decreased. CONCLUSION: This work is the first step to determining the minimum
magnetic shielding required to produce a clinically useful radiation beam from a
coupled MR-Linac system. The fully optimized 3D model more accurately calculates
the electric and magnetic field values since it includes the effects of coupling.
PMID- 28512898
TI - Sci-Sat AM(2): Brachy-01: A novel HDR Ir-192 brachytherapy water calorimeter
standard.
AB - Parameters influencing the accuracy of absorbed dose measurements for HDR 192Ir
brachytherapy using water calorimetry were investigated with the goal to develop
a novel primary absorbed dose to water standard. To provide greater stability,
flexibility, and accuracy in the source-detector distance dsrc-det positioning
and measurement, a new spring-loaded catheter holder composed of two concentric
cylindrical sleeves with multiple orthogonal adjusting screws was developed. The
absorbed dose from Nucletron microSelectron-HDR 192Ir brachytherapy sources with
air kerma strengths ranging between 21000-38000 U was studied. dsrc-det is
optimized so as to balance signal-to-noise ratio (decreasing with increasing dsrc
det ) and temperature drift effects resulting from source self-heating. The
irradiation times were adjusted to yield a minimum 1 Gy of dose at the
measurement point. Successful measurements at dsrc-det ranging between 25-50 mm
were performed. COMSOL MULTIPHYSICSTM software was used to determine the heat
loss correction due to conduction defined as the ratio between temperature rise
at a point under ideal conditions to realistic conditions (i.e., no conduction).
An agreement of better than 6.5% was observed between TG-43 calculated and
calorimetrically measured absorbed dose rates. The effects of convection where
calculated to be negligible as the glass vessel provides a convective barrier
significantly decoupling the water velocity in the interior and exterior of the
vessel (water velocities were 1-2 orders of magnitude different). Our work paves
the way to successful primary absorbed dose determination for radioactive sources
using calorimetric techniques.
PMID- 28512899
TI - Sci-Fri AM: YIS-02: Evaluation of the LabPET4 imaging capabilities for in vivo
small animal imaging.
AB - Positron Emission Tomography (PET) is a non-invasive technique to visualize
metabolic and physiological processes in vivo. Excellent imaging capabilities
such as spatial resolution and count rate performance are essential to achieve
accurate information about the observed processes. It is for this purpose that
the LabPET scanner, an avalanche photodiode (APD)-based fully digital scanner PET
scanner, was initially developed. Two variants of the scanner exist: LabPET4 and
LabPET8 with 3.75 and 7.5 cm axial lengths respectively. The range of the
transaxial FOV is up to 10 cm therefore it can easily accommodate mice and rats.
The aim of this work is to evaluate LabPET4 imaging in several phantoms and small
animals. Spatial resolution was determined using a point source and hot spots
phantoms. The latter were used to assess recovery coefficients (RC) obtained by
taking the ratio of hot spot maximum values compared to the biggest spot maximum
value. FBP reconstructed tangential/radial resolution is 1.3/1.4 mm FWHM (2.5/2.4
FWTM) at the field of view center. With an Ultra Micro Hot Spot Phantom, 1 mm
spots are clearly resolved. Count rate performance was obtained for mouse-size
and rat-size phantoms. For mouse phantom, scatter fraction is 18%, noise
equivalent count rate (NEC) peak is 120 kcps at 5.6 mCi and true coincidences
peak is 215 kcps at 6.6 mCi. Mice and rats were imaged with Na18F and 18FDG.
LabPET4 imaging capabilities achieve state-of-the-art requirements for molecular
imaging and therefore can provide excellent quality images.
PMID- 28512900
TI - Sci-Fri PM: Planning-03: Fundamental understanding of the inter-relation of arc
range, angular dose rate and MLC leaf position optimization of Intensity
Modulated Arc Therapy for a concave target.
AB - Intensity Modulated Arc Therapy (IMAT) is a rotational variant of Intensity
Modulated Radiation Therapy (IMRT) that can be implemented with or without
angular dose rate optimization. The purpose of this study is to determine the
inter-relationship among arc range, Multi-Leaf Collimator (MLC) leaf positions
and angular dose rate optimizations for IMAT delivery of a concave target. A
concave planning target volume (PTV) with central cylindrical organ at risk (OAR)
was used in dissecting the inter-relationships. Plans with full and limited arc
range were generated using leaf position optimization (LPO) alone, angular dose
rate optimization (ADRO) alone or LPO followed by ADRO. Two initial IMAT arcs
were conformal avoidance arcs created with 5 degrees angular increments where
MLC leaf positions were determined from the beams eye view to irradiate the PTV
but avoid the OAR. The objective function value (evaluating dose to PTV and OAR),
a conformity index, dose homogeneity index, mean dose to OAR and normal tissues
were computed and used to evaluate the treatment plans. Dose rate variations and
MLC leaf movements as a function of gantry angle were examined in this approach.
The results demonstrate that LPO followed by ADRO provided the lowest objective
function values, best conformity and dose homogeneity indices, and third in mean
dose to OAR and normal tissues for the complete arc range. Future work will
address different strategies for simultaneously optimizing both the MLC leaf
positions and the variable angular dose rate for IMAT delivery and compare single
and multiple arc plans.
PMID- 28512901
TI - Sci-Sat AM(1): Imaging-02: Comparison between experimental measurements and Monte
Carlo simulations for the off-focal radiation in diagnostic x-ray systems.
AB - In a typical x-ray tube, off-focal radiation is mainly generated by the
backscattered electrons that re-enter the anode outside the focal spot. In an
earlier study, the EGSnrc/BEAMnrc system was modified to be able to properly
transport the anode backscattered electrons, and to tally their subsequent
generation of off-focal x-rays. In the current study, a diagnostic system and a
recent digital mammography system are simulated using the modified BEAMnrc code,
and the simulation results are compared with experimental measurements from the
literature. Simulation results show excellent agreement with experimental
measurements for the spectral shape of both the primary and the off-focal
components, and also for the integral off-focal-to-primary ratio. The spectrum of
the off-focal component at the patient plane is softer than the primary, which
causes a slight softening in the overall spectrum. For a given configuration, the
off-focal component increases with tube voltage because of the increased
probability for off-focal x-rays to escape the anode self-filtration and the
total filtration. This study validates our earlier implementation of off-focal
radiation in EGSnrc/BEAMnrc, and provides a well-benchmarked tool that simulates
x-ray tubes more realistically. The macro to add this feature to BEAMnrc is
available from the authors.
PMID- 28512902
TI - Sci-Sat AM(2): Brachy-05: Dosimetry effects of the TG-43 approximations for two
iodine seeds in LDR brachytherapy.
AB - PURPOSES: This work consists of studying the interseed and tissue composition
effects for two model iodine seeds: the IBt Interseed-125 and the 6711 model
seed. MATERIALS & METHODS: Three seeds were modeled with the MCNP MC code in a
water sphere to evaluate the interseed effect. The dose calculated at different
distances from the centre was compared to the dose summed when the seeds were
simulated separately. The tissue composition effect was studied calculating the
radial dose function for different tissues. Before carrying out post-implant
studies, the absolute dose calculated by MC was compared to experiment results:
with LiF TLDs in an acrylic breast phantom and with an EBT Gafchromic film placed
in a water tank. Afterwards, the TG-43 approximation effects were studied for a
prostate and breast post-implant. RESULTS AND DISCUSSION: The interseed effect
study shows that this effect is more important for model 6711 (15%) than for IBt
(10%) due to the silver rod in 6711. For both seed models the variations of the
radial dose function as a function of the tissue composition are quasi similar.
The absolute dose comparisons between MC calculations and experiments give good
agreement (inferior to 3% in general). For the prostate and breast post-implant
studies, a 10% difference between MC calculations and the TG-43 is found for both
models of seeds. CONCLUSION: This study shows that the differences in dose
distributions between TG43 and MC are quite similar for the two models of seeds
and are about 10% for the studied post-implant treatments.
PMID- 28512903
TI - Sci-Fri AM: YIS-06: On-line adaptive radiation therapy based on the intra
fractional digital tomosynthesis images.
AB - PURPOSE: To investigate the feasibility of performing on-line adaptive radiation
therapy (ART) based on the intra-fractional digital tomosynthesis (DTS) images.
METHOD AND MATERIALS: Intra-fractional DTS images were reconstructed as the
gantry rotated between treatment positions. An edge detection algorithm was used
to automatically segment the DTS images as the gantry arrived at each treatment
position. The original treatment plan was then re-optimized for the most recent
DTS image contours and dose was delivered from each treatment position based on
the newly re-optimized plan. Plan re-optimization was performed using modified
direct aperture optimization (DAO). To test our system, a model representing
typical prostate, bladder and rectum anatomy was generated. First, a treatment
plan based on this original anatomy was created using our DAO system. To simulate
prostate deformations, three clinically relevant deformations (small, medium and
large) were modeled by systematically deforming the original anatomy. The ability
of our approach to adapt the original treatment plan and account for the anatomy
deformations was investigated. RESULTS: Based on the dose-volume constraints from
the RTOG 0415 prostate protocol, the original treatment plan would have been
clinically unacceptable for all three deformations. Using our approach to on-line
ART, the original treatment plan was successfully adapted to arrive at a
clinically acceptable plan for all three anatomy deformations. CONCLUSION: We
have shown that performing on-line ART based on intra-fractional DTS images is
feasible. The advantages are reduced treatment time and the ability to detect and
account for patient motion during the treatment fraction.
PMID- 28512904
TI - Sci-Fri PM: Planning-07: A low diffusion radiochromic gel dosimeter for three
dimensional radiation dosimetry.
AB - PURPOSE: To develop a low diffusion radiochromic leuco crystal violet (LCV)
hydrogel utilizing micelles, for three-dimensional (3-D) radiation dosimetry.
METHOD AND MATERIALS: Concentrations of LCV dye, Triton X-100 and trichloroacetic
acid were varied to determine the optimal gel sensitivity for optical computed
tomography (CT). Using a laser optical CT scanner at lambda = 594 nm, diffusion
rate measurements were performed on half-irradiated (6 MV x-rays) cuvette gel
samples made with and without surfactant, respectively. A cylindrical 1 L gel
volume was irradiated with a 12 MeV electron beam (Varian Clinac 2100C) to a dose
of 30 Gy and scanned with cone- beam optical CT at lambda ~ 590 nm (VistaTM,
Modus Medical Devices Inc.). RESULTS: The most radiation sensitive gel
formulation was found to be: 1 mM LCV, 4 mM Triton X-100, 30 mM trichloroacetic
acid and 4% gelatin. The diffusion rates of a LCV gel without and with surfactant
present were about 2 and 20 times lower than the Fricke xylenol-orange gel
system, respectively. Comparison of the central axis gel attenuation coefficients
normalized at depth of maximum dose (dmax ) with TG21-corrected ion chamber data,
were in agreement, thus, indicating energy and dose-rate independence.
CONCLUSION: Radiochromic LCV micelle gels show minimal diffusion effects and a
dose response that is linear, energy and dose-rate independent. Optical CT
scanned LCV micelle gels are a promising system for 3-D dose verification.
CONFLICT OF INTEREST: Two of the authors (JB, KJ) have a licensing agreement with
Modus Medical Devices Inc. concerning the commercialization of VistaTM.
PMID- 28512905
TI - Sci-Fri AM: YIS-08: Prototype fan beam optical computed tomography scanner for
three-dimensional dose verification in radiation therapy.
AB - A prototype, rapid, high precision fan beam optical computed tomography (OptCT)
scanner for three-dimensional polymer gel dosimetry of complex radiotherapy
protocols has been developed. The scanner employs a sixty degree fan beam of 543
nm laser light to interrogate irradiated gel samples up to 19 cm in cross
sectional diameter. Rapid data acquisition with minimal scattered light and
minimal refraction and reflection artefacts is achieved with the unique radial
design of the front and back apertures of the index matching medium tank,
concentric arrangement of a CNC machined collimator and five photodiode detector
arrays for light detection. Characteristics of the scanner include: an SNR of
optical absorbance in light field projections of up to 100:1; SNR of optical
absorbance in transmission projections of up to 92:1 for phantoms with
absorbances ranging from 0.1 to 1.0 and a spatial resolution of 0.25 mm. OptCT
dose maps extracted from normoxic NIPAM polymer gels irradiated with (a) a
rectangular 3*3 cm2 field, (b) a 4-field wedged treatment and (c) a C-shaped IMRT
plan are examined and compared to the Eclipse TPS. For these treatments, dose
resolution is examined in steep and moderate dose gradient regions using dose
difference and gamma function metrics. The effect of different OptCT
reconstruction parameters on ring and streaking artefacts is also demonstrated.
PMID- 28512906
TI - Sci-Fri PM: Planning-09: An EGSnrc investigation of ion chamber response to Co-60
beams.
AB - The EGSnrc Monte Carlo code was evaluated for its ability to calculate the
relative response of a variety of ion chambers to Co-60 beams as a means of
justifying the use of this code in future investigations of cavity theory. EGSnrc
calculations were compared to measurements with four separate ion chambers, which
were each configured with several wall materials (ranging from plastic to lead)
and cavity sizes (or cavity air pressures). The experimental results included
measurements by Nilsson et al. in 1992, and experiments by Whyte, Attix et al.
and Cormack and Johns in the mid-to-late 1950's designed to evaluate Spencer
Attix cavity theory. Experiments by Whyte involved measurements of the response
per unit mass as a function of cavity air pressure for a large cylindrical
chamber, whereas the other experiments consisted of measurements of the response
per unit mass (or ionization current) as a function of the distance between the
front and back wall (cavity height) of a plane-parallel chamber. EGSnrc
calculations, which could account for the change in response associated with
changes in wall material in most cases, were generally within 1-3% of
experimental values, even for experimental data that required calculations of
unreported wall corrections determined using experimental techniques. The ability
of EGSnrc to accurately model these experiments, which showed variations up to
300%, confirms its suitability for detailed Monte Carlo studies of cavity theory.
PMID- 28512907
TI - Sci-Sat AM(1): Imaging-08: Small animal APD PET detector with submillimetric
resolution for molecular imaging.
AB - Visualization and quantification of biological processes in mice, the preferred
animal model in most preclinical studies, require the best possible spatial
resolution in positron emission tomography (PET). A new 64-channel avalanche
photodiode (APD) detector module was developed to achieve submillimeter spatial
resolution for this purpose. The module consists of dual 4 * 8 APD arrays mounted
in a custom ceramic holder. Individual APD pixels having an active area of 1.1 *
1.1 mm2 at a 1.2 mm pitch can be fitted to an 8 * 8 LYSO scintillator block
designed to accommodate one-to-one coupling. An analog test board with four 16
channel preamplifier ASICs was designed to be interfaced with the existing LabPET
digital processing electronics. At a standard APD operating bias, a mean energy
resolution of 27.5 +/- 0.6% was typically obtained at 511 keV with a relative
standard deviation of 13.8% in signal amplitude for the 64 individual pixels.
Crosstalk between pixels was found to be well below the typical lower energy
threshold used for PET imaging applications. With two modules in coincidence, a
global timing resolution of 5.0 ns FWHM was measured. Finally, an intrinsic
spatial resolution of 0.8 mm FWHM was measured by sweeping a 22Na point source
between two detector arrays. The proposed detector module demonstrates promising
characteristics for dedicated mouse PET imaging at submillimiter resolution.
PMID- 28512908
TI - Sci-Fri AM: YIS-01: Comprehensive MR distortion correction: Phantom validation
and in-vivo application.
AB - MR images provide excellent diagnostic information; however, their treatment
planning utility is limited due to geometric uncertainties from both system and
patient related sources. Despite this concern, interest in developing MR-based
treatment planning protocols is on the rise because of the ease with which
clinically relevant structures can be identified in MR. Here we present our
systematic approach to quantifying both machine (gradient non-linearity and B0
inhomogeneity) and patient (susceptibility and chemical shift) distortions.
Gradient non-linearities were previously measured using a 3D grid phantom while
the remaining types of distortion were measured using a double gradient echo scan
to obtain a B0 distortion map specific to each object/patient. Distortion
measurement and correction were validated on phantoms and then implemented on a
volunteer. B0 inhomogeneity and susceptibility distortions were simulated by
offsetting the x2 -y2 shims; maximum absolute distortion was reduced from 5.4 mm
to 1.0 mm and mean (+/- standard deviation) was reduced from 1.7 +/- 1.4 mm to
0.4 +/- 0.2 mm. Chemical shift distortion was qualitatively evaluated using a
phantom containing fat and water inserts; displacement of the fat signal was much
improved following distortion correction. Intensity correction was validated
using a uniformity phantom and undistorted image profiles were compared to
distorted image profiles and to profiles corrected for geometric and
geometric/intensity distortion; the need for intensity correction was clearly
demonstrated. Once all types of distortion correction were validated on phantoms,
the technique was implemented on a volunteer brain image. Both GE and multi-shot
EPI images were corrected.
PMID- 28512909
TI - Sci-Fri PM: Planning-02: MRI-based radiation treatment planning for an MRI-linac
system.
AB - At Cross Cancer Institute, we are investigating a novel MRI-linac system
consisting of a bi-planar 0.2 T permanent magnet coupled with a 6 MV Linac. The
system can freely revolve axially around the patient to deliver dose from any
desired angle. For such a system, the radiation treatment planning procedure is
expected to rely on the MR images only, i.e. MRI Simulation. Replacing the
current CT/CT+MRI-based RTP procedure with MRI Simulation will eliminate the need
for the planning CT scanning sessions (no additional x-ray exposure) and
consequently the image fusion between MRI and planning CT. In this work, we
propose a comprehensive MRI-based RTP procedure for an MRI-Linac system.
Specifically, the method consists of a) data acquisition, b) analysis and
correction of image artifacts caused by the scanner-related and patient-induced
distortions, c) segmentation of organ structures relevant to dosimetric
calculations (e.g. soft tissue, bone, air), d) conversion of MR images into CT
like images by assigning bulk electron density values to organ contours defined
at step c), e) dose calculations in external magnetic field, and f) plan
evaluation. Monte Carlo simulations were performed to determine the linac-MRI
scanner's magnetic field induced effects on the dose deposited patterns using
patient data. Specifically, we investigated the dosimetric differences between
the corresponding MRI-based RT plans simulated at zero and 0.2 T. We found that
the maximum percent differences for brain studies were within 4%. Most of these
differences occurred at the inferior field edge and superficially at beam exits.
PMID- 28512910
TI - Sci-Sat AM(1): Imaging-01: Tumour and normal tissue T2 and ADC distributions for
a mouse model at 9.4T.
AB - Magnetic resonance (MR) measurements of relaxation times and diffusion
coefficient in tissue have been demonstrated to be sensitive to biological
changes induced by radiation therapy. We are currently using mouse models of
human glioblastoma multiforme (GBM) to study tumour response to ionizing
radiation by MRI at 9.4T. Utilizing conventional imaging techniques coupled with
quantitative measurements of transverse relaxation time (T2) and apparent
diffusion coefficient (ADC), we monitor changes during tumour growth and
subsequent changes after single-fraction radiotherapy. In addition to tumour
parameters, we have measured T2 and ADC in other structures that appear in the
same transverse slices as tumour tissue. Here we report the measured
distributions of T2 and ADC in tumour and in normal tissues that are likely to be
encountered during MR imaging of tumour xenografts in mice, including liver,
kidney, fat, skeletal muscle, spinal cord, and brain. Quantitative knowledge of
these distributions in normal tissue is important in optimizing the sequences
used for imaging of these tissues, and in optimizing continued measurements of T2
and ADC changes. Knowledge of parameter distributions in tumour is important
because recent studies have suggested that the T2 and ADC responses after therapy
may be the result of large shifts in smaller isolated pockets of tumour, rather
than more moderate shifts in T2 and ADC over the whole tumour volume. These
distributions provide a baseline measurement of typical distributions in advance
of radiation therapy.
PMID- 28512911
TI - Sci-Sat AM(2): Brachy-04: Spectral and dosimetric study of the Xoft electronic
brachytherapy system.
AB - The Axxent developed by Xoft Inc. is a miniature x-ray tube capable of generating
a 50 kVp x-ray spectrum with dose-rates suitable for HDR applications. Results of
spectral measurements compared with Geant4 Monte Carlo simulations have been
published. This study is a continuation of previous work with shifting emphasis
towards dosimetric characterization of the miniature x-ray tube. Dose
distributions using EBT Gafchromic films agree to within 10 % of Geant4 results.
In addition, TG-43 parameters can be calculated. However, consideration should be
given to the biological effectiveness of the spectrum at different depths.
Spectral measurements show significant beam hardening with 1st HVL increasing
from 0.55 to 1.20 mm Al after 11.50 mm of water filtration. This effect may be
attributed to the significant loss of low energy characteristic photons.
Furthermore, the degree of beam hardening is dependent of the material, with 1st
HVLs of 1.20 and 1.03 mm Al after 11.50 mm of water and Lucite respectively. The
biological effect is quantified by calculating the number of single and double
strand breaks. The number of strand breaks for the 50 kVp x-ray spectrum is
similar to that of I-125 radiation.
PMID- 28512912
TI - Sci-Fri AM: YIS-05: A new guidance device for lateral-approach stereotactic
breast biopsy.
AB - Stereotactic breast biopsy (SBB) is the gold standard for noninvasive breast
cancer diagnosis. Current systems rely on one of two methods for needle
insertion: a top-approach (from above the breast compression plate) or a lateral
approach (parallel to the compression plate). While the top-approach is more
commonly used, it is not feasible in patients with thin breasts (less than 2.5 cm
thickness after compression), or with superficial lesions. We present a novel
design of lateral guidance support for SBB, which addresses these limitations of
the top-approach, and provides improvements over existing lateral support
hardware. This device incorporates spherical linkages to allow two degrees of
rotational freedom in the needle trajectory for increased targeting flexibility,
as well as an adjustable rigid needle support to minimize needle deflection
within the tissue. Needle placement error in SBB experiments is compared using
both the new lateral guidance device and a commercial lateral guidance device in
agar phantoms. The effect of elevation angle on needle placement accuracy using
the new lateral guidance device is also assessed. Finally, a biopsy accuracy
experiment is presented using a certified SBB phantom to compare the new design
and the commercial lateral guidance device. In these experiments, SBB performed
using the new lateral guidance device results in improved needle placement error
and biopsy accuracy, while increasing targeting flexibility and maintaining
procedural workflow.
PMID- 28512913
TI - Sci-Fri PM: Planning-06: Verification of a Monte Carlo based treatment planning
system in a homogeneous water phantom.
AB - In this abstract we present the results of the verification of the XVMC based
treatment planning system "PrecisePLAN" (release 2.50; Elekta). We investigated a
6 MV photon beam from an Elekta Synergy linear accelerator in a homogeneous water
phantom. Measurements of profiles, percentage depth dose curves (pdds) and
relative output factors (ROFs) for square fields of sides 3, 5, 7, 10, 15, 20 and
30 cm were compared to calculations performed with PrecisePLAN and simulations
with BEAMnrc and DOSXYZnrc. Following recommendations from the literature we
investigated the deviations between measurements and calculations of the profiles
and pdds in four regions and checked for the criterion of acceptability (given in
parenthesis): the inner region (3 %, 2 % at the central axis), the penumbra (2 mm
distance to agreement), the outer region (3 %) and the build up region (2 mm).
The mean deviation +/- 1.5 times the standard deviation should lie within the
confidence interval of the thresholds quoted above. For the ROFs we found very
good agreement with the measurement. The deviations are lower than two and one
percent for PrecisePLAN and BEAMnrc, respectively, for the investigated field
sizes. Also most of the profiles and pdds fulfill the criteria of acceptability
given above, but for the large field sizes some of the profiles and pdds fall
outside the threshold values. The overall agreement between measurements and
calculations, especially for the clinically relevant situations in modern
conformal/IMRT techniques, is clinically acceptable.
PMID- 28512914
TI - Sci-Sat AM(1): Imaging-05: Analytical scatter estimation for cone-beam computed
tomography.
AB - A significant challenge to the implementation of cone-beam computed tomography
(CBCT) for high-resolution imaging is the high scatter to primary ratio. Scatter
causes cupping and shading artifacts, increased noise and decreased contrast in
reconstructed images. Methods to reduce the impact of scatter in CBCT are thus
very desirable. We are investigating methods for computational scatter estimation
and compensation for CBCT, with the goal of incorporating a scatter estimator
within a statistical reconstruction algorithm. We have developed an analytical
method for estimating single scatter, based on Klein-Nishina cross-sections. We
have compared scatter estimates generated with this method with the results of
high-count EGSnrc Monte Carlo simulations. The analytical estimates compare
favorably with the Monte Carlo estimates. The paper will discuss our method for
analytical estimation of single scatter, including the assumptions and
simplifications required to render it computationally tractable, along with the
results of the comparison between the analytical method and Monte Carlo
simulations. The paper will extend previous results obtained with small (40 * 40
* 40 voxel) homogeneous computational phantoms to include results for larger,
more clinically relevant phantoms (128 * 128 * 128 voxels, simulated 50/50 breast
tissue with inserts of varying contrast). The paper will also discuss
computational acceleration obtained through the use of parallel processing via
the WestGrid High-Performance Computing network.
PMID- 28512915
TI - BOOKS AND PUBLICATIONS.
PMID- 28512916
TI - Regulation of bone mass through pineal-derived melatonin-MT2 receptor pathway.
AB - Tryptophan, an essential amino acid through a series of enzymatic reactions gives
rise to various metabolites, viz. serotonin and melatonin, that regulate distinct
biological functions. We show here that tryptophan metabolism in the pineal gland
favors bone mass accrual through production of melatonin, a pineal-derived
neurohormone. Pineal gland-specific deletion of Tph1, the enzyme that catalyzes
the first step in the melatonin biosynthesis lead to a decrease in melatonin
levels and a low bone mass due to an isolated decrease in bone formation while
bone resorption parameters remained unaffected. Skeletal analysis of the mice
deficient in MT1 or MT2 melatonin receptors showed a low bone mass in MT2-/- mice
while MT1-/- mice had a normal bone mass compared to the WT mice. This low bone
mass in the MT2-/- mice was due to an isolated decrease in osteoblast numbers and
bone formation. In vitro assays of the osteoblast cultures derived from the MT1-/
and MT2-/- mice showed a cell intrinsic defect in the proliferation,
differentiation and mineralization abilities of MT2-/- osteoblasts compared to WT
counterparts, and the mutant cells did not respond to melatonin addition.
Finally, we demonstrate that daily oral administration of melatonin can increase
bone accrual during growth and can cure ovariectomy-induced structural and
functional degeneration of bone by specifically increasing bone formation. By
identifying pineal-derived melatonin as a regulator of bone mass through MT2
receptors, this study expands the role played by tryptophan derivatives in the
regulation of bone mass and underscores its therapeutic relevance in
postmenopausal osteoporosis.
PMID- 28512918
TI - Postpartum contraceptive choices among women attending a well-baby clinic in
Ghana.
AB - OBJECTIVE: To assess postpartum contraceptive choices among women attending a
well-baby clinic in Ghana. METHODS: From April 1 to May 31, 2011, a descriptive
cross-sectional survey was conducted among women who attended the well-baby
clinic of Komfo Anokye Teaching Hospital, Kumasi, at 6-24 months after delivery.
Participants were consecutively recruited and interviewed using semi-structured
questionnaires. Data were collected on demographics, exposure to family planning
counseling, message content, and postpartum contraceptive choices. Differences
between the profiles of women who did or did not take up postpartum family
planning were assessed. RESULTS: Of the 200 women enrolled, 44 (22.0%) wanted no
more children and the last pregnancy was unintended among 88 (44.0%). In all, 110
(55.0%) women took up postpartum contraception, with the calendar method (n=57;
51.8%) and injectable contraceptives (n=22; 20.0%) cited as popular choices.
Family planning counseling was received at the prenatal clinic by 47 (23.5%)
women, with 12 (6.0%) given written referrals on the postnatal ward. More
previous contraceptive users than previous non-users chose long-acting or
permanent postpartum methods (P<0.001). CONCLUSION: Inadequate postpartum family
planning counseling and referrals during maternity care were recorded, suggesting
that a comprehensive educational intervention is required to improve uptake.
PMID- 28512919
TI - Influence of serum lipids on the incidence and progression of diabetic
retinopathy and macular oedema: Sankara Nethralaya Diabetic Retinopathy
Epidemiology And Molecular genetics Study-II.
AB - IMPORTANCE: The importance of lipids on incidence and progression of diabetic
retinopathy has not been studied in the Indian population. BACKGROUND: To
elucidate the influence of serum lipid control on the incidence and progression
of diabetic retinopathy and diabetic macular oedema in subjects with type 2
diabetes. DESIGN: Population-based longitudinal observational study in a hospital
setting. PARTICIPANTS: Eight hundred ninety subjects were examined at baseline
and follow-up. METHODS: Diabetic retinopathy was graded per Modified Early
Treatment Diabetic Retinopathy Study scales; 45 degrees , 4-field dilated
stereoscopic digital photography was performed with an additional 30 degrees , 7
field for those who had retinopathy. Macular oedema was evaluated per Proposed
International Clinical Diabetic Retinopathy and Diabetic Macular Oedema Disease
Severity Scales. MAIN OUTCOME MEASURES: Association of serum lipids and incidence
and progression of diabetic retinopathy. RESULTS: Poor control of total
cholesterol was associated with the incidence of sight-threatening retinopathy
(odds ratio = 7.2 [95% confidence interval: 1.5-34.3], P = 0.012) and macular
oedema (odds ratio = 5.5 [95% confidence interval: 1.4-27.4], P = 0.037) after
adjusting for potential confounders. Poor control of triglycerides was associated
with progression to proliferative diabetic retinopathy (odds ratio = 3.2 [95%
confidence interval: 1.1-10.5], P = 0.048). Risk for incident macular oedema (P =
0.041) and progression to proliferative diabetic retinopathy (P = 0.028) was
greater when all lipid types were abnormal. CONCLUSIONS AND RELEVANCE: Poor
control of lipids is a risk factor for incidence of and progression to late
stages of retinopathy. Abnormal levels of all lipid types are associated with
risk of incident macular oedema and progression to proliferative diabetic
retinopathy.
PMID- 28512917
TI - Nomenclature for factors of the HLA system, update February 2017.
PMID- 28512920
TI - An audit of adherence to heart failure guidelines in an Australian hospital: A
pharmacist perspective.
AB - RATIONALE, AIMS, AND OBJECTIVES: The Australian National Heart Foundation
Guidelines have been developed to guide clinicians on how to best manage chronic
heart failure (CHF) patients according to the current best available evidence.
The primary aim of this study is to evaluate the proportion of patients
prescribed evidence-based therapy (EBT) for CHF on discharge at this Australian
metropolitan hospital and factors affecting its prescribing. The secondary aims
are to examine the proportion of patients prescribed EBT on discharge on cardiac
wards compared to medical wards and to explore the role of the pharmacist in the
management of these patients. METHOD: A retrospective audit of patients' medical
notes who were admitted consecutively for CHF management was conducted over 6
months to examine their management. RESULTS: The results showed at discharge, a
total of 52% of patients were discharged on angiotensin converting enzyme
inhibitors/angiotensin receptor blockers, 49% were discharged on beta-blockers,
15% were on Aldosterone receptor antagonists, 90% were discharged on diuretics,
and 29% were discharged on Digoxin. The main determinants of prescribing EBT on
discharge were the presence of prescribing contraindications and patients'
comorbidities. Patients discharged from cardiac wards were more likely to be
prescribed EBT than if discharged on medical wards. Furthermore, in the subset of
the cohort who was reviewed by a pharmacist during admission, a higher percentage
of patients were discharged on EBT compared with those who did not have a
pharmaceutical input. CONCLUSION: This study highlighted existing gaps between
the National CHF Guidelines and clinical prescribing practice in this hospital.
Patients who were discharged from cardiac wards were more likely to be prescribed
medications concordant with the guidelines, and there is further opportunity for
pharmacists to assist in closing gaps in prescribing practice by the promotion of
adherence to these guidelines.
PMID- 28512921
TI - Web-based integrated bipolar parenting intervention for parents with bipolar
disorder: a randomised controlled pilot trial.
AB - BACKGROUND: People with bipolar disorder (BD) experience additional parenting
challenges associated with mood driven fluctuations in communication, impulse
control and motivation. This paper describes a novel web-based self-management
approach (Integrated Bipolar Parenting Intervention; IBPI) to support parents
with BD. METHOD: Parents with BD with children aged 3-10 years randomised to IBPI
plus treatment as usual (TAU) or waitlist control (WL). IBPI offered 16 weeks
access to interactive self-management information concerning BD and parenting
issues. Feasibility was through recruitment, retention and web usage. Clinical
outcomes were assessed at baseline, 16, 24, 36 and 48 weeks. TRIAL REGISTRATION
NUMBER: ISRCTN75279027. RESULTS: Ninety seven participants were recruited with
98% retention to end of intervention and 90% to final follow-up (56%-94% data
analysed of retained participants; higher rates for observer measures). 77% of
IBPI participants accessed the website (53% accessed parenting modules). Child
behaviour, parenting sense of competence and parenting stress improved
significantly in IBPI compared to WL to end of intervention, sustained to 48
weeks. Impacts of IBPI on family functioning, parent mood and time to mood
relapse were not significant. CONCLUSIONS: Online self-management support for
parents with BD is feasible, with promising improvements in parenting and child
behaviour outcomes. A definitive clinical and cost-effectiveness trial is
required to confirm and extend these findings.
PMID- 28512922
TI - Effect of chemical immobilization of SDF-1alpha into muscle-derived scaffolds on
angiogenesis and muscle progenitor recruitment.
AB - The availability of three-dimensional bioactive scaffolds with enhanced
angiogenic capacity that have the capability to recruit tissue specific resident
progenitors is of great importance for the regeneration of impaired skeletal
muscle. Here, we have investigated whether introduction of chemoattractant
factors to tissue specific extracellular matrix promotes cellular behaviour in
vitro as well as muscle progenitor recruitment and vascularization in vivo. We
developed an interconnective macroporous sponge from decellularized skeletal
muscle with maintained biochemical traits of the intact muscle. SDF-1alpha, a
potent cell homing factor involved in muscle repair, was physically adsorbed or
chemically immobilized in these muscle-derived sponges. The immobilized sponges
showed significantly higher SDF-1alpha conjugation efficiency along with improved
metabolism and infiltration of muscle-derived stem cells in vitro, and thus
generated uniform cellular constructs. In vivo, femoral muscle implantation in
rats revealed a negligible immune response in all scaffold groups. We observed
enhanced engraftment, neovascularization, and infiltration of CXCR4+ cells in the
immobilized-SDF-1alpha sponge compared with nonimmobilized controls. Although
Pax7+ cells identified adjacent to the immobilized-SDF-1alpha implantation site,
other factors appear to be necessary for efficient penetration of Pax7+ cells
into the sponge. These findings suggest that immobilization of cell homing
factors via chemical mediators can result in recruitment of cells to the
microenvironment with subsequent improvement in angiogenesis.
PMID- 28512923
TI - The Braden Scale, A standard tool for assessing pressure ulcer risk, predicts
early outcomes after liver transplantation.
AB - The Braden Scale is a standardized tool to assess pressure ulcer risk that is
reported for all hospitalized patients in the United States per requirements of
the Center for Medicare and Medicaid Services. Previous data have shown the
Braden Scale can predict both frailty and mortality risk in patients with
decompensated cirrhosis. Our aim was to evaluate the association of the Braden
Scale score with short-term outcomes after liver transplantation (LT). We
performed a retrospective cohort study of deceased donor LT recipients at 2
centers and categorized them according to the Braden Scale at hospital admission
as low (>18), moderate (16-18), or high risk (<16) for pressure ulcer. We created
logistic and Poisson multiple regression models to evaluate the association of
Braden Scale category with in-hospital and 90-day mortality, length of stay
(LOS), nonambulatory status at discharge, and discharge to a rehabilitation
facility. Of 341 patients studied, 213 (62.5%) were low risk, 59 (17.3%) were
moderate risk, and 69 (20.2%) were high risk. Moderate- and high-risk patients
had a greater likelihood for prolonged LOS, nonambulatory status, and discharge
to a rehabilitation facility, as compared with low-risk patients. High-risk
patients additionally had increased risk for in-hospital and 90-day mortality
after LT. Multiple regression modeling demonstrated that high-risk Braden Scale
score was associated with prolonged LOS (IRR, 1.56; 95% confidence interval [CI],
1.47-1.65), nonambulatory status at discharge (odds ratio [OR], 4.15; 95% CI,
1.77-9.71), and discharge to a rehabilitation facility (OR, 5.51; 95% CI, 2.57
11.80). In conclusion, the Braden Scale, which is currently assessed in all
hospitalized patients in the United States, independently predicted early
disability-related outcomes and greater LOS after LT. Liver Transplantation 23
1153-1160 2017 AASLD.
PMID- 28512925
TI - Nitrogen-fixing tree abundance in higher-latitude North America is not
constrained by diversity.
AB - The rarity of nitrogen (N)-fixing trees in frequently N-limited higher-latitude
(here, > 35 degrees ) forests is a central biogeochemical paradox. One hypothesis
for their rarity is that evolutionary constraints limit N-fixing tree diversity,
preventing N-fixing species from filling available niches in higher-latitude
forests. Here, we test this hypothesis using data from the USA and Mexico. N
fixing trees comprise only a slightly smaller fraction of taxa at higher vs.
lower latitudes (8% vs. 11% of genera), despite 11-fold lower abundance (1.2% vs.
12.7% of basal area). Furthermore, N-fixing trees are abundant but belong to few
species on tropical islands, suggesting that low absolute diversity does not
limit their abundance. Rhizobial taxa dominate N-fixing tree richness at lower
latitudes, whereas actinorhizal species do at higher latitudes. Our results
suggest that low diversity does not explain N-fixing trees' rarity in higher
latitude forests. Therefore, N limitation in higher-latitude forests likely
results from ecological constraints on N fixation.
PMID- 28512931
TI - Characterization of a C60o unit at a secondary standard dosimetry laboratory:
Monte Carlo simulations compared to measurements and results from the literature.
AB - PURPOSE: To compare a Monte Carlo (MC) characterization of a C60o unit at the
Swedish Secondary Standard Dosimetry Laboratory (SSDL) with the results of both
measurements and literature with the aims of (1) resolving a change in the ratio
of air-kerma free in air Kair and absorbed dose to water Dw in a water phantom
noted experimentally after a source exchange in the laboratory and (2) reviewing
results from the literature on similar MC simulations. Although their use in
radiotherapy is decreasing, the characteristics of C60o beams are of interest
since C60o beams are utilized in calibrating ionization chambers for the absolute
dosimetry of radiotherapy beams and as reference radiation quality in evaluating
the energy dependence of radiation detectors and in studies on radiobiological
effectiveness. METHODS: The BEAMnrc MC code was used with a detailed geometrical
model of the treatment head and two models of the C60o source representing the
sources used before and after source exchange, respectively. The active diameters
of the C60o sources were 1.5 cm in pellet form and 2.0 cm in sintered form.
Measurements were performed on the actual unit at the Swedish SSDL. RESULTS:
Agreement was obtained between the MC and the measured results within the
estimated uncertainties for beam profiles, water depth-dose curve, relative air
kerma output factors, and for the ratios of Kair/Dw before and after source
exchange. The on-axis energy distribution of the photon fluence free in air for
the unit loaded with its present (1.5 cm in diameter) source agreed closely with
the results from the literature in which a source of the same make and active
diameter, inside a different treatment head, was simulated. The spectrum for the
larger (2.0 cm in diameter) source was in close agreement with another published
spectrum, also modeling a C60o source with an active diameter of 2.0 cm inside a
different treatment head. CONCLUSIONS: The reduction in the value of Kair/Dw
following source exchange was explained by the spectral differences between the
two sources that were larger in the free in-air geometry used for Kair
calibrations than at 5g/cm2 depth in the water phantom used for Dw calibrations.
Literature review revealed differences between published in-air C60o spectra
derived for sources of different active diameters, and investigators in need of
an accurately determined C60o in-air spectrum should be aware of differences due
to source active diameter.
PMID- 28512983
TI - A radiobiological investigation on dose and dose rate for permanent implant
brachytherapy of breast using I125 or P103d sources.
AB - PURPOSE: The present report addresses the question of what could be the
appropriate dose and dose rate for I125 and P103d permanent seed implants for
breast cancer as monotherapy for early stage breast cancer. This is addressed by
employing a radiobiological methodology, which is based on the linear quadratic
model, to identify a biologically effective dose (BED) to the prescription point
of the brachytherapy implant, which would produce equivalent cell killing (or
same cell survival) when compared to a specified external radiotherapy scheme.
METHODS: In the present analysis, the tumor and normal tissue BED ratios of
brachytherapy and external radiotherapy are examined for different combinations
of tumor proliferation constant (K), alpha/beta ratios, initial dose rate (R0),
and reference external radiotherapy scheme (50 or 60 Gy in 2 Gy per fraction).
The results of the radiobiological analysis are compared against other reports
and clinical protocols in order to examine possible opportunities of improvement.
RESULTS: The analysis indicates that physical doses of approximately 100-110 Gy
delivered with an initial dose rate of around 0.05Gyh-1 and 78-80 Gy delivered at
0.135Gyh-1 for I125 and P103d permanent implants, respectively, are equivalent to
50 Gy external beam radiotherapy (EBRT) in 2 Gy per fraction. Similarly, for
physical doses of approximately 115-127 Gy delivered with an initial dose rate of
around 0.059Gyh-1 and 92 Gy delivered at 0.157Gyh-1 for I125 and P103d,
respectively, are equivalent to 60 Gy EBRT in 2 Gy per fraction. It is shown that
the initial dose rate required to produce isoeffective tumor response with 50 or
60 Gy EBRT in 2 Gy per fraction increases as the repopulation factor K increases,
even though repopulation is also considered in EBRT. Also, the initial dose rate
increases as the value of the alpha/beta ratio decreases. The impact of the
different alpha/beta ratios on the ratio of the tumor BEDs is significantly large
for both the I125 and P103d implants with the deviation between the
alpha/beta=10.0Gy ratios and those using the 4.0 and 3.5 Gy values ranging
between 18% and 22% in most of the cases. CONCLUSIONS: For the cases of I125 and
P103d, the equivalent physical doses to 50 Gy EBRT in 2 Gy per fraction are
associated with an overdosage of the involved normal tissue in the range of 4%
16% and an underdosage by 10%-15% for a BED for normal tissue, using an
alpha/beta value of 3.0 Gy (BEDNT,3Gy) of 100 Gy. These values are lower by 10%
20% than the published value of 124 Gy for I125 and by about 13% when compared to
the published isoeffective dose of 90 Gy for P103d. Similarly, the equivalent
physical doses to 60 Gy EBRT in 2 Gy per fraction are associated with an
overdosage of the involved normal tissue by 10%-20% and an underdosage by 4%-10%
for BEDNT,3Gy of 110 Gy.
PMID- 28512986
TI - Work climate and the mediating role of workplace bullying related to job
performance, job satisfaction, and work ability: A study among hospital nurses.
AB - AIM: To increase understanding of workplace bullying and its relation to work
climate and different outcomes among nurses. Examine a proposed bullying model
including both job resource and job demands, as well as nurse outcomes reflected
in job performance, job satisfaction, and work ability. BACKGROUND: Workplace
bullying has been identified as some of the most damaging mechanisms in workplace
settings. It is important to increase understanding of workplace bullying in
relation to work climate and different outcomes among nurses. DESIGN: This study
adopted a cross-sectional web based survey design. METHOD: A sample of 2946
Registered Nurses from four public Norwegian hospitals were collected during
October 2014. We analysed data using descriptive statistics, correlations,
Cronbach's alpa, confirmatory factor analyses, and structural equation modelling.
RESULTS: The majority of work climate characteristics confirmed to influence
workplace bullying, and additionally had direct influence on nurse outcomes; job
performance, job satisfaction, and work ability. Bullying had a mediational role
between most of the work climate dimensions and nurse outcomes. CONCLUSION: This
study increases our understanding of organizational antecedent of bullying among
nurses. Workplace bullying among nurses functions as a mediator between the
majority of work climate dimensions and outcomes related to job satisfaction and
work ability. Strategies to reduce bullying should look at the study finding and
specifically job resources and job demands that influence bullying and nurse
outcomes.
PMID- 28512988
TI - Phytochemistry and Pharmacology of Phyllanthus niruri L.: A Review.
AB - Phyllanthus niruri, a typical member of family Euphorbiaceae, is a small annual
herb found throughout the tropical and subtropical regions of both hemispheres.
The genus Phyllanthus has been used in traditional medicine for its wide range of
pharmacological activities like antimicrobial, antioxidant, anticancer,
antiinflammatory, antiplasmodial, antiviral, diuretic and hepatoprotective. This
review summarizes the information about morphological, biochemical,
ethanobotanical, pharmacological, biological and toxicological activities with
special emphasis on mechanism of anticancer activity of P. niruri. Gaps in
previous studies such as taxonomic inconsistency of P. niruri, novel
phytochemicals and their therapeutic properties, especially mechanisms of
anticancerous activity and market products available, have been looked into and
addressed. Scientific information related to 83 phytochemicals (including many
novel compounds detected recently by the authors) has been provided in a very
comprehensive manner. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28512989
TI - The 'golden goddess' of spices: a potentially effective topical therapy for Bowen
disease?
PMID- 28512990
TI - Luminescence, circular dichroism and in silico studies of binding interaction of
synthesized naphthylchalcone derivatives with bovine serum albumin.
AB - Chalcones possess various biological properties, for example, antimicrobial, anti
inflammatory, analgesic, antimalarial, anticancer, antiprotozoal and
antitubercular activity. In this study, naphthylchalcone derivatives were
synthesized and characterized using 1 H NMR 13 C NMR, Fourier transform infrared
and mass techniques. Yields for all derivatives were found to be >90%. Protein
drug interactions influence the absorption, distribution, metabolism and
excretion (ADME) properties of a drug. Therefore, to establish whether the
synthesized naphthylchalcone derivatives can be used as drugs, their binding
interaction toward a serum protein (bovine serum albumin) was investigated using
fluorescence, circular dichroism and molecular docking techniques under
physiological conditions. Fluorescence quenching of the protein in the presence
of naphthylchalcone derivatives, and other derived parameters such as association
constants, number of binding sites and static quenching involving confirmed non
covalent binding interactions in the protein-ligand complex were observed.
Circular dichroism clearly showed changes in the secondary structure of the
protein in the presence of naphthylchalcones, indicating binding between the
derivatives and the serum protein. Molecular modelling further confirmed the
binding mode of naphthylchalcone derivatives in bovine serum albumin. A site
specific molecular docking study of naphthylchalcone derivatives with serum
albumin showed that binding took place primarily in the aromatic low helix and
then in subdomain II. The dominance of hydrophobic, hydrophilic and hydrogen
bonding was clearly visible and was responsible for stabilization of the complex.
PMID- 28512991
TI - Is parity a risk factor for excessive weight gain during pregnancy and postpartum
weight retention? A systematic review and meta-analysis.
AB - The aim of this study was to systematically review and meta-analyse the
associations between parity, pre-pregnancy body mass index (BMI), gestational
weight gain (GWG) and, when included, postpartum weight retention (PPWR). Papers
reporting associations between parity and BMI and/or GWG in adult women were
eligible: 2,195 papers were identified, and 41 longitudinal studies were included
in the narrative synthesis; 17 studies were included in a meta-analysis. Findings
indicated that parity was associated positively with pre-pregnancy BMI. In
contrast, the role of parity in GWG was less clear; both positive and negative
relationships were reported across studies. Parity was not associated directly
with PPWR. This pattern of results was supported by our meta-analysis with the
only significant association between parity and pre-pregnancy BMI. Overall,
parity was associated with higher pre-pregnancy BMI; however, the role of parity
in GWG and PPWR remains unclear, and it is likely that its influence is indirect
and complex. Further research to better understand the contribution of parity to
maternal obesity is warranted.
PMID- 28512992
TI - Association of CD8+ T-cells with bone erosion in patients with rheumatoid
arthritis.
AB - AIM: Bone erosion is a major problem worsening quality of rheumatoid arthritis
(RA) patients' lives. However, causal factors responsible for bone erosion in RA
have remained unclear. We aimed to examine genetic variants conferring bone
erosion in RA using a Korean genome-wide association study (GWAS) and to search
for possible biological mechanisms underlying the development of bone erosion.
METHOD: We obtained genome-wide single nucleotide polymorphism (SNP) data for 711
Korean RA patients using Illumina HapMap 550v3/660W arrays. Associations between
SNPs and bone erosion status based on the Steinbrocker staging system were
examined using multivariate logistic regression. Cell-type-specific enrichment of
the epigenomic chromatin annotation H3K4me3 at the bone erosion associated
variants was further investigated using National Institute of Health Roadmap
Epigenomics data. RESULTS: As we tested the associations between 439 289 SNPs and
bone erosion in 385 patients with erosive RA and 326 with non-erosive RA, none of
the tested SNPs reached the genome-wide significance threshold, although many
loci showed modest genetic effect on bone erosion status with suggestive
association (e.g., rs2741200 [P = 3.75 * 10-6 ] in the SLA-TG locus and
rs12422918 [P = 4.13 * 10-6 ] in SRGAP1). However, the top-ranked SNPs and their
linked proxies, which were mostly located in non-coding variants, were
significantly co-localized with the highly tissue-specific regulatory marker
H3K4me3 in CD8+ memory T-cells (P = 0.014). CONCLUSION: Although, there was no
large-effect variants associated with bone erosion in our GWAS, we have shown
that CD8+ memory T-cells may have relevance with bone erosion in patients with RA
through the analysis of ChiP-seq data.
PMID- 28512993
TI - HLA-Cw6-positive patients with psoriasis show improved response to methotrexate
treatment.
AB - It is well documented that patients with human leucocyte antigen (HLA)-Cw6+ (type
1) psoriasis have increased severity and reduced age of onset of psoriasis.
However, not much is known about any differential response of this genetic
subgroup to various treatments. We set out to determine if there was any genetic
association of the HLA-Cw6 allele with the first-line systemic treatment commonly
used in psoriasis, methotrexate. A cohort of patients from Tayside in Scotland
was recruited through a novel generic consenting process (GoShare); they were
extensively phenotyped and analysed for an association of their HLA-Cw6 genotype
status with treatment outcomes. HLA-Cw6+ patients showed notably improved
response to methotrexate (P = 0.05), and further analysis demonstrated an even
greater response in a subcohort of the HLA-Cw6+ patients, who did not have
concomitant psoriatic arthritis (P = 0.01). HLA-Cw6+ patients also exhibited
fewer treatment-limiting adverse events. In addition to these findings, the
methodology and primary clinical outcome phenotype, which we validate here, will
greatly facilitate replication of the present results in independent cohorts.
PMID- 28512994
TI - Erythema elevatum diutinum presenting with palmoplantar keratoderma.
PMID- 28512995
TI - Alpha-1-antitrypsin deficiency-related panniculitis: two cases with diverse
clinical courses.
AB - Alpha-1-antitrypsin deficiency (AATD)-related panniculitis is an extremely rare
and underdiagnosed entity, and there is a paucity of data on its treatment. We
report two cases of AATD-related panniculitis. The first was a 24-year-old woman
with known AATD who presented with painful leg ulcers refractory to treatment
with corticosteroids and colchicine. She had a good response to alpha1
antitrypsin infusions but required dose adjustment due to flares in disease
activity. The second case was a 38-year-old woman who presented with painful
nodules on the legs refractory to corticosteroid therapy. Laboratory
investigations revealed severe AATD. She had an excellent response to colchicine
therapy. In both these cases of AATD, panniculitis was the first clinical
manifestation of the disease. AATD-related panniculitis may have none of the
typical clinical clues for AATD, such as a family history, cirrhosis or
emphysema. Early identification may help prevent these complications from
developing.
PMID- 28512996
TI - ZL006 promotes migration and differentiation of transplanted neural stem cells in
male rats after stroke.
AB - New strategies must be developed to resolve the problems of stroke treatment. In
recent years, stem cell-based therapy after stroke has come into the public and
academic lens. Previously we have shown that uncoupling neuronal nitric oxide
synthase (nNOS) from the postsynaptic density protein-95 (PSD-95) by ZL006, a
small molecular compound, can ameliorate ischemic damage and promote neuronal
differentiation of endogenous neural stem cells (NSCs) in focal cerebral ischemic
male rats. In this study, we transplanted exogenous NSCs into the ipsilateral
hemisphere of male rats in combination with ZL006 treatment after ischemic
stroke. We show that ZL006 treatment facilitates the migration of transplanted
NSCs into the ischemia-injured area and promotes neuronal differentiation of
these cells, which is not due to a direct effect of ZL006 on exogenous NSCs but
is associated with increased phosphorylation of cAMP response element-binding
protein (CREB) in neurons and favorable microenvironment. Moreover, improved
functional outcome in the ZL006-treated group was also found. Taken together, our
data indicate that ZL006, uncoupling nNOS-PSD-95 in neurons, positively regulates
the fate of transplanted NSCs and benefits the functional outcome after stroke in
male rats.
PMID- 28512997
TI - Research publication performance of Australian Professors of Nursing & Midwifery.
PMID- 28512999
TI - In response to Otolaryngology workforce analysis.
PMID- 28512998
TI - Implementation of Treat-to-Target in Rheumatoid Arthritis Through a Learning
Collaborative: Results of a Randomized Controlled Trial.
AB - OBJECTIVE: Treat-to-target (TTT) is an accepted paradigm for the management of
rheumatoid arthritis (RA), but some evidence suggests poor adherence. The purpose
of this study was to test the effects of a group-based multisite improvement
learning collaborative on adherence to TTT. METHODS: We conducted a cluster
randomized quality-improvement trial with waitlist control across 11 rheumatology
sites in the US. The intervention entailed a 9-month group-based learning
collaborative that incorporated rapid-cycle improvement methods. A composite TTT
implementation score was calculated as the percentage of 4 required items
documented in the visit notes for each patient at 2 time points, as evaluated by
trained staff. The mean change in the implementation score for TTT across all
patients for the intervention sites was compared with that for the control sites
after accounting for intracluster correlation using linear mixed models. RESULTS:
Five sites with a total of 23 participating rheumatology providers were
randomized to intervention and 6 sites with 23 participating rheumatology
providers were randomized to the waitlist control. The intervention included 320
patients, and the control included 321 patients. At baseline, the mean TTT
implementation score was 11% in both arms; after the 9-month intervention, the
mean TTT implementation score was 57% in the intervention group and 25% in the
control group (change in score of 46% for intervention and 14% for control; P =
0.004). We did not observe excessive use of resources or excessive occurrence of
adverse events in the intervention arm. CONCLUSION: A learning collaborative
resulted in substantial improvements in adherence to TTT for the management of
RA. This study supports the use of an educational collaborative to improve
quality.
PMID- 28513000
TI - A hit to current "hit" wisdom: A century later, it's time for a change.
PMID- 28513001
TI - The frequency of urinary tract infection and subclinical bacteriuria in dogs with
allergic dermatitis treated with oclacitinib: a prospective study.
AB - BACKGROUND: Oclacitinib is a selective Janus kinase inhibitor for the treatment
of canine allergic pruritus and atopic dermatitis in dogs. Glucocorticoids and
ciclosporin increase urinary tract infection (UTI) frequency in dogs with
inflammatory skin disease. OBJECTIVE: Prospective study to evaluate the frequency
of UTI and subclinical bacteriuria in dogs with allergic dermatitis receiving
oclacitinib. METHODS: Client-owned dogs >=2 years of age with a history of
allergic dermatitis without apparent history of urinary tract disease or
predisposition to UTI were included. Prior to enrolment, urinalysis and
quantitative urine culture were performed after a washout period of at least 14
days from systemic antimicrobial drugs and 28 days for ciclosporin and systemic
glucocorticoids. Dogs received oclacitinib at labelled dosing for an intended
period of 180-230 days with a follow-up urinalysis and urine culture performed
regardless of urinary tract signs. Systemic antimicrobial and immune-modulating
drugs were not administered during the study. RESULTS: None of the 55 dogs in
this study developed UTI while receiving oclacitinib based on follow-up
urinalysis and urine culture performed during a range of 58-280 days (mean 195
days). Two dogs developed self-limiting abnormal urinary tract signs without
urine culture or urinalysis findings consistent with UTI. CONCLUSIONS AND
CLINICAL IMPORTANCE: These findings indicate that bacteriuria is not an expected
adverse effect in dogs treated with oclacitinib without a prior history of UTI or
predisposing condition during this treatment period. Therefore, routine urine
culture is not indicated for such dogs in the absence of abnormal urinalysis or
clinical signs of urinary tract disease.
PMID- 28513002
TI - One oxygen breath shortened the time to return of spontaneous circulation in
severely asphyxiated piglets.
AB - AIM: Asphyxiated neonates should be resuscitated with air, but it remains unclear
if oxygen supplementation is needed in ineffectively ventilated newborn infants.
We studied the return of spontaneous circulation (ROSC) with oxygen or air in an
experimental model of inadequate ventilation. METHODS: Asphyxia was induced in 16
newborn piglets until their heart rate was <60 bpm or mean arterial pressure
(MAP) <30 mmHg. During the first 10 minutes of resuscitation, they received one
breath per minute of oxygen (n = 8) or air (n = 8). Tidal volume was 7.5 mL/kg.
If MAP was <30 mmHg for 15 seconds, closed-chest cardiac massage (CCCM) was
performed for 45 seconds. From 10 minutes onward, all piglets received normal
ventilation with air. ROSC was defined as a heart rate >150 bpm, MAP >40 mmHg and
no subsequent CCCM. RESULTS: Before resuscitation, the median arterial pH was
6.73. At 10 minutes, no piglets in the oxygen group needed CCCM, while all did in
the air group (p < 0.001). The median time to ROSC was 60 seconds with oxygen and
845 seconds with air (p < 0.001). No brain tissue hyperoxia occurred. CONCLUSION:
When ventilation was inadequate, one oxygen breath reduced time to ROSC in
piglets with severe metabolic and respiratory acidosis.
PMID- 28513003
TI - Quantification of skin erythema response to topical alcohol in alcohol-intolerant
East Asians.
AB - BACKGROUND/PURPOSE: Severe alcohol intolerance characterized by flushing,
headache, nausea, and tachycardia even after very modest oral alcohol
consumption, is common among East Asians (Chinese, Japanese, Koreans) and has
been associated with the accumulation of acetaldehyde resulting from genetic
polymorphism of aldehyde dehydrogenase (ALDH). These individuals also display
erythema of the skin in response to exposure to topical alcohol. We have recently
observed that dietary phytochemicals such as sulforaphane can accelerate the
disposal of acetaldehyde from cells and animals by inducing ALDH. The goal of
this study was to quantify the erythema response of skin to topical alcohol
exposure. METHODS: The erythema response of the forearm skin of healthy Japanese
with unusual alcohol sensitivity evoked by a range of very low doses of alcohol
(2, 4, 8, and 16 MUmol/cm2 ) was determined by means of a chromometer, which
measures a* values (red-green scale). RESULTS: The magnitude of the a* response
(?a*) to alcohol was time- and dose-dependent, but differed considerably among
individuals. It was much higher in those individuals who claimed to be alcohol
intolerant, and ?a* was unrelated to the initial a* values of the skin prior to
alcohol challenge. CONCLUSION: The ?a* index is suitable for the quantitative
determination of topical alcohol-induced erythema response, and the evaluation of
effectiveness of protective strategies against erythema response.
PMID- 28513005
TI - Effects of argument quality, source credibility and self-reported diabetes
knowledge on message attitudes: an experiment using diabetes related messages.
AB - BACKGROUND: Previous studies have reported that credibility and content (argument
quality) are the most critical factors affecting the quality of health
information and its acceptance and use; however, this causal relationship merits
further investigation in the context of health education. Moreover, message
recipients' prior knowledge may moderate these relationships. OBJECTIVES: This
study used the elaboration likelihood model to determine the main effects of
argument quality, source credibility and the moderating effect of self-reported
diabetes knowledge on message attitudes. METHODS: A between-subjects experimental
design using an educational message concerning diabetes for manipulation was
applied to validate the effects empirically. A total of 181 participants without
diabetes were recruited from the Department of Health, Taipei City Government.
Four group messages were manipulated in terms of argument quality (high and low)
* source credibility (high and low). RESULTS: Argument quality and source
credibility of health information significantly influenced the attitude of
message recipients. The participants with high self-reported knowledge
participants exhibited significant disapproval for messages with low argument
quality. CONCLUSION: Effective health information should provide objective
descriptions and cite reliable sources; in addition, it should provide accurate,
customised messages for recipients who have high background knowledge level and
ability to discern message quality.
PMID- 28513004
TI - Effects of encapsulated porcine islets on glucose and C-peptide concentrations in
diabetic nude mice 6 months after intraperitoneal transplantation.
AB - BACKGROUND: In patients with type 1 diabetes, allogeneic islet transplantation
can provide normal HbA1c concentrations, but it requires immunosuppression.
Transplanting encapsulated islets into the peritoneal cavity could reduce or
eliminate the need for immunosuppression. One of the uncertain features of
intraperitoneal islet transplantation is the difficulty of measuring C-peptide
concentrations in peripheral blood, which is often used for the marker of islet
function. We hypothesized that secreted C-peptide from intraperitoneally
transplanted islets was mostly consumed in the peritoneal cavity, which resulted
in low C-peptide concentrations in peripheral blood. METHODS: In each of two
experiments, encapsulated neonatal porcine islets were intraperitoneally
transplanted into four nude mice with streptozotocin-induced diabetes. Three
diabetic nude mice without transplanted islets were used as diabetic controls,
and three untreated healthy nude mice were used as normal controls. Islet
functions were monitored for 2 months in the first experiment and 6 months in the
second experiment. Encapsulated islets were retrieved after each experiment and
evaluated by fluorescein diacetate/propidium iodide tests for the viability and
static glucose-stimulated insulin release tests for the function. C-peptide
concentrations from the blood and from the intraperitoneal cavity at 6 months
were compared. RESULTS: In both experiments, diabetes was reversed in all
transplanted mice, and oral glucose tolerance test showed improved profiles. In
general, retrieved islets were viable and functional. However, blood porcine C
peptide concentrations were low at both 2 and 6 months, and concentrations in the
ascites of peritoneal cavity were 40 times as high as those in blood.
CONCLUSIONS: The peripheral blood sampling for c-peptide, though highly
informative in vascularized grafts, may not be the primary tool for monitoring
the health and function of encapsulated products when transplanted into
intraperitoneal cavity. Our results might explain the clinical feature of the low
C-peptide blood concentrations after successful intraperitoneal encapsulated
islet transplantation.
PMID- 28513027
TI - Sci-Thurs PM: Delivery-02: Improving image quality produced by CCD cameras
exposed to stray radiation from a medical linac.
AB - PURPOSE: Charge coupled devices (CCDs) are increasingly used in radiation
therapy. CCDs are ideal for applications such as two-dimensional dosimetry of
scintillator sheets or to read arrays of miniature scintillation detectors.
However, CCDs are sensitive to stray radiation. Radiation-induced noise strongly
alters images and limits their quantitative analysis. We have characterized
radiation-induced noise and developed filtration algorithms to restore image
quality. METHOD AND MATERIALS: Two models of CCD cameras were used for
measurements in linac environments. Images were acquired with and without
radiation. The structure of the transient noise was characterized. Then, four
methods of noise filtration were compared: median filtering of a time series of
images, uniform median filtering of single images, an adaptive filter with
switching mechanism and a modified version of the adaptive filter. RESULTS: The
intensity distribution of noisy pixels was similar in both cameras. However, the
spatial distribution of the noise was different: the average noise cluster size
was 1.2+/-0.6 and 3.2+/-2.7 pixels for each of the two cameras. The median of a
time series of image resulted in the best filtration and minimal image
distortion. For applications where time series is impractical, adaptive
filtration must be used to reduce image distortion. CONCLUSION: We have
characterized the transient noise produced in CCDs by scattered radiation from a
linac and have developed an efficient filtration scheme to remove this noise and
restore image quality. Use of our filtration scheme allows detailed quantitative
analysis of an image even when subjected to scattered radiation.
PMID- 28513032
TI - COMS eye plaque brachytherapy dosimetry simulations for P103d, I125, and C131s.
AB - Monte Carlo (MC) simulations were performed to estimate brachytherapy dose
distributions for Collaborative Ocular Melanoma Study (COMS) eye plaques.
Brachytherapy seed models 200, 6711, and CS-1 Rev2 carrying P103d, I125, and
C131s radionuclides, respectively, were modeled and benchmarked against
previously published values. Calculated dose rate constants LambdaMC were 0.684,
0.924, and 1.052 cGy h-1 U-1 (+/-2.6%, k=1 uncertainty) for models 200, 6711, and
CS-1 Rev2, respectively. The seeds were distributed into 10, 12, 14, 16, 18, 20,
and 22 mm-diameter COMS eye plaques. Simulations were performed in both
heterogeneous and homogeneous environments, where the latter were in-water and
the former included the silastic seed carrier insert and gold-alloy plaque. MC
based homogenous central axis dose distributions agreed within 2%+/-1% (+/-1
s.d.) to hand-calculated values. For heterogeneous simulations, notable photon
attenuation was observed, with dose reduction at 5 mm of 19%, 11%, and 9% for
P103d, I125, and C131s, respectively. A depth-dependent correction factor was
derived to correct homogenous central-axis dose distributions for plaque
component heterogeneities, which were found to be significant at short radial
distances.
PMID- 28513039
TI - Sci-Thurs PM: Delivery-01: Sliding Window IMRT: Uncertainties of the leading edge
and plateau of the beam profile.
AB - The aim of this work is to analyze the dependence of the dose profile
uncertainties for the sliding window IMRT (SW-IMRT) beams under the condition of
an extreme dose rate (DR) and leaf velocity (LV). The deviations of the edges and
plateau for the beam profiles of small number of MUs delivered using the dynamic
MLC were studied. Field sizes with lengths of 5 and 10 cm were irradiated by
photon beams of 2-8 MU/beam, DR = 100-600 MU/min and LS = 1-5 cm/s. Kodak TL
radiographic films were used in the measurement. The photon beams (6 and 15 MV)
were produced by a Varian 21EX Linac with a 120-leaf MLC. It is found that the
MLC cannot keep the leaves moving with a proper speed continuously under a stable
DR when beam of small MUs are irradiated. For example, the dynamic MLC needs 1.2
s and 12 MU to irradiate a field of 5 cm length with 2 MU using DR = 600 MU/min
and LC = 5 cm/s. The plateau of the beam profile has several sinusoidal periods
of about 150 ms. The magnitude of the plateau uncertainties was about 7% and 15%
for the dose of the beam with DR = 400 and 600 MU/min (2 MU/beam), respectively.
It is concluded that SW-IMRT beams of more than 10 MUs, delivered with 1 cm/s ?
LV ? 5 cm/s and 100 MU/min ? DR ? 600 MU/min, have a good agreement between the
delivered and planned dose profiles.
PMID- 28513041
TI - Erratum: "Out-of-field dose equivalents delivered by proton therapy of prostate
cancer".
PMID- 28513050
TI - Sci-Thurs PM: Delivery-03: Optical imaging of microscopic radiation dose
gradients using a digital microscope.
AB - Using superior localization and immobilization methods, stereotactic radiosurgery
is capable of delivering spheres of dose as small as a few millimetres in
diameter to intracranial targets. For targets abutting critical structures, the
most conformal treatments minimize adverse radiation side effects and it is
important, therefore, to ensure proper quality assurance prior to delivering high
doses of radiation to eloquent brain locations in a single fraction. This work
examines the capability of a digital microscope, with translation stage and
associated software, to resolve dose gradients in Gafchromic EBTTM film at the
micron level. In order to validate the microscope-film system from a radiation
physics approach, films were irradiated to produce very steep penumbrae by using
very small fields, lower photon energies and minimal geometric penumbra
contribution. Orthovoltage film irradiations were done by placing films in
phantom beneath pinhole collimators. The experimentally determined off-axis dose
profiles were compared with Monte Carlo computer simulations which replicated the
irradiation geometry and served to validate our measured data. The measured 80% -
20% penumbral widths were 46 MUm +/- 26 MUm (100 kVp, 2 mm field size) and 69 MUm
+/- 27 MUm (300 kVp, 2 mm field size). In the energy range covered, the measured
penumbral widths agreed with Monte Carlo computer simulations within experimental
uncertainty. The effects of noise originating from both the film and the
microscope system are discussed and improvements to this system suggested.
PMID- 28513052
TI - Primary care and cancer: Facing the challenge of early diagnosis and
survivorship.
AB - With ageing populations and an increasing lifetime risk of cancer, primary care
will continue to play an increasingly important role in early diagnosis and
cancer survivorship, especially with the lowering of risk thresholds for referral
and diagnostic investigations. However, primary care in many countries is in
crisis with increasing workloads for primary care physicians. Potential solutions
to these challenges will be outlined including development of multidisciplinary
teams, diagnostic decision support, increasing access to diagnostics and cost
effective referral pathways.
PMID- 28513053
TI - High-frequency ultrasound quantification of acute radiation dermatitis: pilot
study of patients undergoing radiotherapy for breast cancer.
AB - BACKGROUND: Acute radiation dermatitis (ARD) is a frequent complication after
breast cancer radiotherapy and is usually assessed by semi-quantitative clinical
scores, which may be subject to inter-observer variability. High-frequency
ultrasound imaging of the skin can reliably quantify thickness and edema in
diseased skin. We aimed to compare the relative increase in dermal thickness of
the irradiated zone in breast-cancer patients undergoing radiotherapy, with
clinical severity. METHODS: A consecutive series of patients undergoing treatment
for breast cancer by lumpectomy and radiotherapy in a 6-month period also
underwent clinical and ultrasound evaluation of ARD. RESULTS: We included 34
female patients 17 had grade 1 (group 1), 17 had grade 2 or grade 3 ARD (group
2). The mean relative increase in dermal thickness in irradiated skin (RIDTIS)
was greater for group 2 than 1: 0.53 vs 0.29 mm (P=.023). On univariate analysis,
ARD was associated with skin phototype, breast volume and RIDTIS, and on
multivariable analysis, breast volume and age remained predictive of the disease.
CONCLUSION: Patients with more severe dermatitis showed significantly increased
dermal thickness. Dermal thickness is a quantitative variable that could help
quantify the efficacy of drugs and improve the treatment of this disease in
patients undergoing radiotherapy.
PMID- 28513054
TI - Is there a common motor dysregulation in sleepwalking and REM sleep behaviour
disorder?
AB - This study sought to determine if there is any overlap between the two major non
rapid eye movement and rapid eye movement parasomnias, i.e. sleepwalking/sleep
terrors and rapid eye movement sleep behaviour disorder. We assessed adult
patients with sleepwalking/sleep terrors using rapid eye movement sleep behaviour
disorder screening questionnaires and determined if they had enhanced muscle tone
during rapid eye movement sleep. Conversely, we assessed rapid eye movement sleep
behaviour disorder patients using the Paris Arousal Disorders Severity Scale and
determined if they had more N3 awakenings. The 251 participants included 64
patients with rapid eye movement sleep behaviour disorder (29 with idiopathic
rapid eye movement sleep behaviour disorder and 35 with rapid eye movement sleep
behaviour disorder associated with Parkinson's disease), 62 patients with
sleepwalking/sleep terrors, 66 old healthy controls (age-matched with the rapid
eye movement sleep behaviour disorder group) and 59 young healthy controls (age
matched with the sleepwalking/sleep terrors group). They completed the rapid eye
movement sleep behaviour disorder screening questionnaire, rapid eye movement
sleep behaviour disorder single question and Paris Arousal Disorders Severity
Scale. In addition, all the participants underwent a video-polysomnography. The
sleepwalking/sleep terrors patients scored positive on rapid eye movement sleep
behaviour disorder scales and had a higher percentage of 'any' phasic rapid eye
movement sleep without atonia when compared with controls; however, these
patients did not have higher tonic rapid eye movement sleep without atonia or
complex behaviours during rapid eye movement sleep. Patients with rapid eye
movement sleep behaviour disorder had moderately elevated scores on the Paris
Arousal Disorders Severity Scale but did not exhibit more N3 arousals (suggestive
of non-rapid eye movement parasomnia) than the control group. These results
indicate that dream-enacting behaviours (assessed by rapid eye movement sleep
behaviour disorder screening questionnaires) are commonly reported by
sleepwalking/sleep terrors patients, thus decreasing the questionnaire's
specificity. Furthermore, sleepwalking/sleep terrors patients have excessive
twitching during rapid eye movement sleep, which may result either from a higher
dreaming activity in rapid eye movement sleep or from a more generalised non
rapid eye movement/rapid eye movement motor dyscontrol during sleep.
PMID- 28513055
TI - Breastfeeding in the context of domestic violence-a cross-sectional study.
AB - AIMS: To determine the differences in breastfeeding among women who did and did
not experience domestic violence during pregnancy and postpartum in a Swedish
context. In addition, to identify possible differences regarding breastfeeding
between groups with or without a history of violence. Further, determine the
relationship between exclusive breastfeeding and symptoms of depression.
BACKGROUND: History of violence may increase the risk of depression and a
decrease in, or cessation of, breastfeeding. DESIGN: The study has a cross
sectional design. METHODS: Data were collected prospectively from March 2012 -
May 2015. A cohort of 731 mothers answered a questionnaire from a larger project
(1.5 years postpartum). RESULTS: Breastfeeding was reported by 93.7% of
participants. Women exposed to domestic violence during pregnancy and/or
postpartum (4.5%) were just as likely to breastfeed as women who had not reported
exposure to domestic violence. There were no statistically significant
differences between the groups with or without a history of violence regarding
exclusive breastfeeding. Women reporting several symptoms of depression breastfed
exclusively to a lesser extent compared with women who had a few symptoms of
depression. CONCLUSION: Domestic violence did not influence breastfeeding
prevalence or duration. Breastfeeding did not differ in women with or without a
history of violence. Symptoms of depression influenced duration of exclusive
breastfeeding. Beyond recognizing women who are exposed to violence, it is
important to identify and to support pregnant women and new mothers with symptoms
of depression as their health and the health of their infants depends on the
mothers' mental well-being.
PMID- 28513056
TI - Lessons learned from a pilot study of an Indigenous patient navigator
intervention in Queensland, Australia.
AB - Indigenous patient navigator (IPN) programmes show promise in addressing barriers
to cancer care and facilitation of patient self-efficacy. The purpose of this
paper is to describe and reflect upon the experience of training an IPN and
implementation of the intervention in the Australian context with Indigenous
cancer patients. Randomised clinical trial might provide the best available
evaluation measure of an intervention but caution should be taken in the
implementation process. Socio-cultural aspects and training can affect the
conduct of this type of intervention. We report here five issues needing
consideration prior to implementing such intervention. Specifically: (1)
recognition of the collective bonds within Indigenous community and understanding
by IPN of the degree of personal assistance perceived as not intrusive by the
patient; (2) conduct ongoing evaluation of the different role of an IPN involved
in this intervention care provider vs. researcher. (3) meaningful engagement
develops from a trusting/collaborative relationship between research team and
study site staff which may not occur in the study time frame; (4) existing skills
as well as training provided may not translate in the IPN understanding and
aligning with the study objectives/research values; (5) recruitment of
participants requires innovative and highly flexible strategies to be successful.
PMID- 28513057
TI - Systemic inflammation and alterations to cerebral blood flow in obstructive sleep
apnea.
AB - Systemic inflammation and alterations to regional cerebral blood flow (CBF) have
been reported previously in obstructive sleep apnea (OSA). This study utilized
arterial spin labelling (ASL) perfusion magnetic resonance imaging (MRI) to
evaluate CBF in OSA patients and determine its relationship with systemic
inflammation. Twenty male patients with moderate and severe OSA [apnea-hypopnea
index (AHI) >15] and 16 healthy male volunteers (AHI <5) were recruited. Early-
or late-phase changes in leucocyte apoptosis and its subsets were determined by
flow cytometry. Perfusion MRI data were acquired with a pulsed continuous ASL
technique. The CBF maps were compared using voxel-based statistics to determine
differences between the OSA and control groups. The differences in CBF, clinical
severity and leucocyte apoptosis were correlated. Exploratory groupwise
comparison between the two groups revealed that the OSA patients exhibited low
CBF values in the vulnerable regions. The lower regional CBF values were
correlated with higher clinical disease severity and leucocyte apoptosis. OSA
impairs cerebral perfusion in vulnerable regions, and this deficit is associated
with increased disease severity. The apparent correlation between systemic
inflammation and cerebral perfusion may be indicative of haemodynamic alterations
and their consequences in OSA.
PMID- 28513058
TI - Pro-myogenic and low-oxygen culture increases expression of contractile smooth
muscle markers in human fibroblasts.
AB - Smooth muscle cells (SMCs) are essential for tissue engineering strategies to
fabricate organs such as blood vessels, the oesophagus and bladder, and to create
disease models of these systems. In order for such therapies and models to be
feasible, SMCs must be sourced effectively to enable production of large numbers
of functional cells. In vitro, SMCs divide slowly and demonstrate short
proliferative lifespans compared with other types of cells, including stem cells
and fibroblasts, limiting the number of cells that can be derived from expansion
in culture of a primary isolation. As such, it would be beneficial to better
understand the factors underlying induction and maintenance of SMC phenotypes, in
order to produce new sources of SMCs for tissue engineering and disease
modelling. Here we report the ability of human dermal fibroblasts to display
patterns of gene expression resembling contractile SMCs when cultured under
conditions that are known to promote a contractile phenotype in SMCs, including
culture on collagen IV, low-serum culture, TGF-beta1 treatment and hypoxia. These
factors drive expression of the myogenic transcription factor myocardin, as well
as expression of several of its gene targets that are known contributors to
contractile phenotype in SMCs, including smooth muscle alpha actin, calponin, and
myosin heavy chain. Our results suggest that culture conditions associated with
culture of SMCs may be sufficient to induce myogenic gene expression patterns and
potential myogenic function in non-muscle cells.
PMID- 28513060
TI - Increased oral inflammation, leukocytes, and leptin, and lower adiponectin in
overweight or obesity.
AB - OBJECTIVES: The association between body mass index (BMI) and oral diseases was
investigated, and levels of obesity-related inflammatory mediators were
evaluated. SUBJECTS AND METHODS: Participants (n = 160) were clinically and
radiographically examined for oral diseases. Blood profiles were recorded. Levels
of adiponectin, leptin, and C-reactive protein (CRP) were measured. RESULTS: One
hundred and thirteen (70.6%) participants had overweight or obese status (BMI >=
23.0 kg/m2 ). Sum of dental diseases and severe periodontitis were higher in
overweight or obese individuals than in normal-weight participants (p = .037 and
p = .002, respectively). A significant difference in oral mucosal disorders
between normal weight and overweight or obesity was not found. Plasma leukocyte
counts, liver enzymes, leptin, and CRP levels were increased while adiponectin
levels were decreased in individuals with BMI>=23.0 kg/m2 compared with normal
weight participants. After adjusting for age, sex, fasting plasma glucose level,
smoking, and exercise, obesity was associated with sum of dental diseases (beta =
0.239, p = .013), severe periodontitis (OR=4.52; 95% CI 1.37, 14.95, p = .013),
adiponectin (beta = -0.359, p < .001), leptin (beta = 0.630, p < .001), and CRP
levels (OR=12.66; 95% CI 3.07, 52.21, p < .001). CONCLUSION: Overweight or obese
Thai people were related to an increase in inflammatory dental and periodontal
diseases with an altered health profile and plasma inflammatory mediators.
PMID- 28513061
TI - Disorder-specific versus generic cognitive-behavioral treatment of anxiety
disorders in children and young people: a systematic narrative review of evidence
for the effectiveness of disorder-specific CBT compared with the disorder-generic
treatment, Coping Cat.
AB - BACKGROUND: Coping Cat (CC), a generic cognitive-behavioral intervention for
anxiety disorders in children and young people, is recommended in the United
Kingdom for social anxiety disorder (SAD), generalized anxiety disorder,
separation anxiety (SA), and specific phobias (SP), with disorder-specific
approaches generally favored in treatment of anxiety disorders in adults.
OBJECTIVES: To compare CC with disorder-specific cognitive-behavioral therapy
(CBT) interventions based on anxiety-related treatment outcomes. STUDY SELECTION:
Primary research articles describing treatment of children and young people aged
7-17 for SAD, generalized anxiety disorder, SA, and SP, using CC or disorder
specific CBT. RESULTS: Ten studies implemented CC and four implemented disorder
specific CBT. One study compared CC with a disorder-specific approach. There was
a lack of data to support use of CC in treatment of SPs. However, CC was equally
effective as disorder-specific treatments for SA and SAD. CONCLUSIONS: A lack of
data exists for disorder-specific CBT interventions compared to CC.
PMID- 28513059
TI - Fluoxetine and congenital malformations: a systematic review and meta-analysis of
cohort studies.
AB - AIMS: To investigate the safety of fluoxetine use during pregnancy, and to better
understand the relationship between maternal fluoxetine use during the first
trimester and congenital malformations in infants. METHODS: PubMed and Web of
Science databases were systematically searched from inception to 21 March 2016.
Additional studies were identified in a manual search of the reference lists. Two
reviewers independently extracted data. A third reviewer checked the data.
Estimates were pooled using a random-effects model to calculate the summarized
relative ratios (RR) and 95% confidence intervals (CI). RESULTS: Among 1918
initially identified articles, 16 cohort studies were included. The offspring of
pregnant women exposed to fluoxetine during the first trimester had a
statistically increased risk of major malformations (RR = 1.18, 95% CI = 1.08
1.29), cardiovascular malformations (RR = 1.36, 95% CI = 1.17-1.59), septal
defects (RR = 1.38, 95% CI = 1.19-1.61), and non-septal defects (RR = 1.39, 95%
CI = 1.12-1.73) with low heterogeneity in infants. There were no significant
observations of other system-specific malformations in the nervous system, eye,
urogenital system, digestive system, respiratory system, or musculoskeletal
system, respectively. There was no indication of publication bias. CONCLUSIONS:
The results of this meta-analysis indicate maternal fluoxetine use is associated
with a slightly increased risk of cardiovascular malformations in infants. Health
care providers and pregnant women must weigh the risk-benefit potential of these
drugs when making decisions about whether to treat with fluoxetine during
pregnancy.
PMID- 28513063
TI - Challenges and opportunities for addressing adolescent cyberbullying within the
context of clinically meaningful psychological outcomes.
PMID- 28513062
TI - What are the family needs when a parent has mental health problems? Evidence from
a systematic literature review.
AB - PROBLEM: Little evidence exists showing how a given high-risk group of children
born to parents with poor mental health seek help and how care may be improved in
order to better reach and support their families. METHODS: A systematic
literature review was undertaken to identify the needs and help-seeking behaviors
of children and their parents. Through an analysis of both quantitative and
qualitative studies, published in German- and English-speaking research
literature, the needs of children and parents were identified and categorized.
Findings concerning their help-seeking behavior and the influence of demographic
variables on needs and help-seeking behaviors were also described. FINDINGS: In
the primary studies, the most identified parental needs were "the need for being
a good parent"; "worries about the child's well-being"; and "the need for
practical help." For children, the categories identified included "the need for
knowledge"; "worries about parent's well-being"; and "the need for normality."
However, information about help-seeking behaviors and influences of demographic
factors was fairly limited in the literature. CONCLUSIONS: In families with
parental mental health problems, it seems especially important to take a family
focused approach. The individual needs of children (and their families) should
shape the planning of treatment and nursing care.
PMID- 28513065
TI - Catalyst-Controlled Regiodivergent Alkyne Insertion in the Context of C-H
Activation and Diels-Alder Reactions: Synthesis of Fused and Bridged Cycles.
AB - Rhodium(III)- and cobalt(III)-catalyzed C-H activation of indoles and coupling
with 1,6-enynes is discussed. Under rhodium(III) catalysis, the alkyne insertion
follows 2,1-regioselectivity with a subsequent type-I intramolecular Diels-Alder
reaction (IMDA) to afford [6,5]-fused cycles. When catalyzed by the cobalt(III)
congener, 1,2-insertion of the alkyne is preferred, and followed by a rare type
II IMDA, thus leading to bridged [3,3,1]-cycles. This selectivity of the alkyne
insertion was mainly tuned by the steric sensitivity of the catalyst.
PMID- 28513064
TI - Autofluorescence of collagen fibres in scar.
AB - BACKGROUND/PURPOSE: Autofluorescence has become an important factor associated
with diagnosis and treatment of many diseases. METHODS: Full thickness skin
grafts and scar biopsies were obtained from five volunteers. The normal skin or
scar tissue paraffin-wax sections were stained with HE and the autofluorescence
of collagen fibres was viewed under fluorescence microscopy. RESULTS: In normal
skin, the autofluorescence was showed in dermis, specifically in collagen fibres.
There was very weak autofluorescence in epidermis. The spectrum was excited at
488 nm and the peak value of autofluorescence was significantly different between
reticular layer (169.24+/-9.18) and papillar layer of dermis (103.91+/-15.23). In
scar tissue, the autofluorescence was showed in collagen fibres and the peak
value was 176.71+/-20.69. The structure of collagen fibres in normal skin or scar
tissue was different in loose degree, thickness, boundle size, and morphology by
their autofluorescence. CONCLUSION: The different peak value of autofluorescence
between scar and normal skin may due to the different density of collagen fibtes
in them. This study may provide us a simple and effective assessment indicator
and method for diagnosis and treatment of scar.
PMID- 28513066
TI - Sexual selection, speciation and constraints on geographical range overlap in
birds.
AB - The role of sexual selection as a driver of speciation remains unresolved, not
least because we lack a clear empirical understanding of its influence on
different phases of the speciation process. Here, using data from 1306 recent
avian speciation events, we show that plumage dichromatism (a proxy for sexual
selection) does not predict diversification rates, but instead explains the rate
at which young lineages achieve geographical range overlap. Importantly, this
effect is only significant when range overlap is narrow (< 20%). These findings
are consistent with a 'differential fusion' model wherein sexual selection
reduces rates of fusion among lineages undergoing secondary contact, facilitating
parapatry or limited co-existence, whereas more extensive sympatry is contingent
on additional factors such as ecological differentiation. Our results provide a
more mechanistic explanation for why sexual selection appears to drive early
stages of speciation while playing a seemingly limited role in determining broad
scale patterns of diversification.
PMID- 28513067
TI - Interventions for cutaneous molluscum contagiosum.
AB - BACKGROUND: Molluscum contagiosum is a common skin infection that is caused by a
pox virus and occurs mainly in children. The infection usually resolves within
months in people without immune deficiency, but treatment may be preferred for
social and cosmetic reasons or to avoid spreading the infection. A clear evidence
base supporting the various treatments is lacking.This is an update of a Cochrane
Review first published in 2006, and updated previously in 2009. OBJECTIVES: To
assess the effects of specific treatments and management strategies, including
waiting for natural resolution, for cutaneous, non-genital molluscum contagiosum
in people without immune deficiency. SEARCH METHODS: We updated our searches of
the following databases to July 2016: the Cochrane Skin Group Specialised
Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched six trial registers
and checked the reference lists of included studies and review articles for
further references to relevant randomised controlled trials. We contacted
pharmaceutical companies and experts in the field to identify further relevant
randomised controlled trials. SELECTION CRITERIA: Randomised controlled trials of
any treatment of molluscum contagiosum in people without immune deficiency. We
excluded trials on sexually transmitted molluscum contagiosum and in people with
immune deficiency (including those with HIV infection). DATA COLLECTION AND
ANALYSIS: Two review authors independently selected studies, assessed
methodological quality, and extracted data from selected studies. We obtained
missing data from study authors where possible. MAIN RESULTS: We found 11 new
studies for this update, resulting in 22 included studies with a total of 1650
participants. The studies examined the effects of topical (20 studies) and
systemic interventions (2 studies).Among the new included studies were the full
trial reports of three large unpublished studies, brought to our attention by an
expert in the field. They all provided moderate-quality evidence for a lack of
effect of 5% imiquimod compared to vehicle (placebo) on short-term clinical cure
(4 studies, 850 participants, 12 weeks after start of treatment, risk ratio (RR)
1.33, 95% confidence interval (CI) 0.92 to 1.93), medium-term clinical cure (2
studies, 702 participants, 18 weeks after start of treatment, RR 0.88, 95% CI
0.67 to 1.14), and long-term clinical cure (2 studies, 702 participants, 28 weeks
after start of treatment, RR 0.97, 95% CI 0.79 to 1.17). We found similar but
more certain results for short-term improvement (4 studies, 850 participants, 12
weeks after start of treatment, RR 1.14, 95% CI 0.89 to 1.47; high-quality
evidence). For the outcome 'any adverse effect', we found high-quality evidence
for little or no difference between topical 5% imiquimod and vehicle (3 studies,
827 participants, RR 0.97, 95% CI 0.88 to 1.07), but application site reactions
were more frequent in the groups treated with imiquimod (moderate-quality
evidence): any application site reaction (3 studies, 827 participants, RR 1.41,
95% CI 1.13 to 1.77, the number needed to treat for an additional harmful outcome
(NNTH) was 11); severe application site reaction (3 studies, 827 participants, RR
4.33, 95% CI 1.16 to 16.19, NNTH over 40).For the following 11 comparisons, there
was limited evidence to show which treatment was superior in achieving short-term
clinical cure (low-quality evidence): 5% imiquimod less effective than cryospray
(1 study, 74 participants, RR 0.60, 95% CI 0.46 to 0.78) and 10% potassium
hydroxide (2 studies, 67 participants, RR 0.65, 95% CI 0.46 to 0.93); 10%
Australian lemon myrtle oil more effective than olive oil (1 study, 31
participants, RR 17.88, 95% CI 1.13 to 282.72); 10% benzoyl peroxide cream more
effective than 0.05% tretinoin (1 study, 30 participants, RR 2.20, 95% CI 1.01 to
4.79); 5% sodium nitrite co-applied with 5% salicylic acid more effective than 5%
salicylic acid alone (1 study, 30 participants, RR 3.50, 95% CI 1.23 to 9.92);
and iodine plus tea tree oil more effective than tea tree oil (1 study, 37
participants, RR 0.20, 95% CI 0.07 to 0.57) or iodine alone (1 study, 37
participants, RR 0.07, 95% CI 0.01 to 0.50). Although there is some uncertainty,
10% potassium hydroxide appears to be more effective than saline (1 study, 20
participants, RR 3.50, 95% CI 0.95 to 12.90); homeopathic calcarea carbonica
appears to be more effective than placebo (1 study, 20 participants, RR 5.57, 95%
CI 0.93 to 33.54); 2.5% appears to be less effective than 5% solution of
potassium hydroxide (1 study, 25 participants, RR 0.35, 95% CI 0.12 to 1.01); and
10% povidone iodine solution plus 50% salicylic acid plaster appears to be more
effective than salicylic acid plaster alone (1 study, 30 participants, RR 1.43,
95% CI 0.95 to 2.16).We found no statistically significant differences for other
comparisons (most of which addressed two different topical treatments). We found
no randomised controlled trial evidence for expressing lesions or topical
hydrogen peroxide.Study limitations included no blinding, many dropouts, and no
intention-to-treat analysis. Except for the severe application site reactions of
imiquimod, none of the evaluated treatments described above were associated with
serious adverse effects (low-quality evidence). Among the most common adverse
events were pain during application, erythema, and itching. Included studies of
the following comparisons did not report adverse effects: calcarea carbonica
versus placebo, 10% povidone iodine plus 50% salicylic acid plaster versus
salicylic acid plaster, and 10% benzoyl peroxide versus 0.05% tretinoin.We were
unable to judge the risk of bias in most studies due to insufficient information,
especially regarding concealment of allocation and possible selective reporting.
We considered five studies to be at low risk of bias. AUTHORS' CONCLUSIONS: No
single intervention has been shown to be convincingly effective in the treatment
of molluscum contagiosum. We found moderate-quality evidence that topical 5%
imiquimod was no more effective than vehicle in terms of clinical cure, but led
to more application site reactions, and high-quality evidence that there was no
difference between the treatments in terms of short-term improvement. However,
high-quality evidence showed a similar number of general side effects in both
groups. As the evidence found did not favour any one treatment, the natural
resolution of molluscum contagiosum remains a strong method for dealing with the
condition.
PMID- 28513069
TI - Predict pancreatic fistula after pancreaticoduodenectomy: ratio body
thickness/main duct.
AB - BACKGROUND: The occurrence of post-operative pancreatic fistula (POPF) after
pancreaticoduodenectomy is a challenging issue. The aim was to identify variables
on preoperative computed tomography (CT) scan, useful to predict clinically
significant POPF (grades B-C) after pancreaticoduodenectomy. METHODS: Patients
presented POPF after pancreaticoduodenectomy were included from two tertiary
referral centres. B/W ratio was defined by ratio of pancreas body thickness (B)
to main pancreatic duct (W). The predictive parameters of POPF on CT scan were
assessed with a receiving operator characteristics (ROC) curve and intrinsic
characteristics. RESULTS: Between 2010 and 2013, 186 patients who underwent
pancreaticoduodenectomy were included. POPF occurred in 25% of them, and was
clinically significant in 13%. After univariate analysis, endocrine tumours (P =
0.03), main pancreatic duct size (P < 0.01) and B/W ratio (P = 0.04) were
significantly associated with POPF. ROC curve showed a greater area under curve
for B/W ratio (0.68) than for main pancreatic duct size (0.33). A 3.8 threshold
displayed 80 and 51% for sensibility and specificity, respectively, and a
negative predictive value of 94%. A B/W ratio >3.8 increased the rates of post
operative haemorrhage (odds ratio = 4.3 (1.4-13.2), P = 0.01), and reintervention
(odds ratio = 3.4 (1.2-9.6), P = 0.02). CONCLUSIONS: B/W ratio superior to 3.8
assessed on preoperative CT scan may be an easy tool to predict clinically
significant POPF after pancreaticoduodenectomy.
PMID- 28513068
TI - A randomized controlled trial: branched-chain amino acid levels and glucose
metabolism in patients with obesity and sleep apnea.
AB - There is evidence that changes in branched-chain amino acid (BCAA) levels may
correlate with the efficacy of therapeutic interventions for affecting
improvement in metabolic control. The objective of this study was to evaluate
whether serum concentrations of BCAAs (leucine, isoleucine, valine) could mediate
in insulin sensitivity and glucose tolerance after continuous positive airway
pressure (CPAP) treatment in patients with obstructive sleep apnea (OSA). A
prospective randomized controlled trial of OSA patients with morbid obesity was
conducted. Eighty patients were randomized into two groups: 38 received
conservative treatment and 42 received CPAP treatment for 12 weeks. Plasma levels
of BCAA, glucose tolerance and insulin resistance were evaluated at baseline and
after treatment. After treatment, significant decreases of leucine levels were
observed in both groups when compared with baseline levels (P < 0.005). With
respect to patients with normal glucose tolerance (NGT), patients with impaired
glucose tolerance (IGT) had higher baseline levels of isoleucine (78 +/- 16
versus 70 +/- 13 MUmol L-1 , P = 0.014) and valine (286 +/- 36 versus 268 +/- 41
MUmol L-1 , P = 0.049), respectively. Changes in levels of leucine and isoleucine
after treatment were related negatively to changes in fasting plasma glucose and
glycosylated haemoglobin values only in the conservative group (P < 0.05). In
summary, we found that the treatment with CPAP for 12 weeks caused similar
changes in circulating BCAAs concentrations to conservative treatment and a
differential metabolic response of CPAP and conservative treatment was observed
between the relationship of BCAAs and glucose homeostasis. Additional studies are
needed to determine the interplay between branched-chain amino acids and glucose
metabolism in patients with sleep apnea.
PMID- 28513070
TI - Influence of quercetin on the interaction of gliclazide with human serum albumin
spectroscopic and docking approaches.
AB - Protein-binding interactions are displacement reactions which have been
implicated as the causative mechanisms in many drug-drug interactions. Thus, the
aim of presented study was to analyse human serum albumin-binding displacement
interaction between two ligands, hypoglycaemic drug gliclazide and widely
distributed plant flavonoid quercetin. Fluorescence analysis was used in order to
investigate the effect of substances on intrinsic fluorescence of human serum
albumin (HSA) and to define binding and quenching properties of ligand-albumin
complexes in binary and ternary systems, respectively. Both ligands showed the
ability to bind to HSA, although to a different extent. The displacement effect
of one ligand from HSA by the other one has been described on the basis of the
quenching curves and binding constants comparison for the binary and ternary
systems. According to the fluorescence data analysis, gliclazide presents a
substance with a lower binding capacity towards HSA compared with quercetin.
Results also showed that the presence of quercetin hindered the interaction
between HSA and gliclazide, as the binding constant for gliclazide in the ternary
system was remarkably lower compared with the binary system. This finding
indicates a possibility for an increase in the non-bound fraction of gliclazide
which can lead to its more significant hypoglycaemic effect. Additionally,
secondary and tertiary structure conformational alterations of HSA upon binding
of both ligands were investigated using synchronous fluorescence, circular
dichroism and FT-IR. Experimental data were complemented with molecular docking
studies. Obtained results provide beneficial information about possible
interference upon simultaneous co-administration of the food/dietary supplement
and drug.
PMID- 28513071
TI - Juvenile idiopathic arthritis in multiplex families: longitudinal follow-up.
AB - OBJECTIVE: To describe the physical, social, educational and employment status
and clinical outcomes of patients with juvenile idiopathic arthritis (JIA) from
multiplex families. METHODS: All familial JIA patients were treated and had
regular follow-up between 1990 and 2015 at King Faisal Specialist Hospital and
Research Center (KFSH-RC), Riyadh, were included. Demographic data, disease
duration, active arthritis and articular and extra-articular damage at last
follow-up visit were reviewed. Additionally, social, educational and employment
history were obtained via personal or phone interviews. RESULTS: Twenty-three
patients (20 females) belonging to 10 families were included. The mean age was
14.6 (+/-9) years with mean disease duration of 11.4 (+/-9) years and mean follow
up duration of 10.5 (+/-6). Fourteen patients had systemic JIA while eight
patients had polyarticular subtype, and one patient had psoriatic arthritis. All
patients received concomitant treatment. Twenty-one patients commenced biologic
agents; treatment switched to another agent in all of them because of inadequate
response. Most patients had progressive disease course. Twelve patients had
active polyarthritis and 22 patients showed evidence of articular damage. All
patients had raised inflammatory markers. Eighteen patients had short stature and
11 patients had delayed puberty. Two patients had lower limb lymphedema and one
patient had a single kidney with refractory hypertension. Three patients
underwent hip arthroplasty. Seventeen patients had satisfactory educational
achievement and four patients were in employment. Two patients died due to
infection. CONCLUSION: Our results showed the largest familial clusters of JIA in
the Middle East. Patients with familial JIA had refractory disease with
progressive disease course.
PMID- 28513072
TI - Self-Assembly and Local Manipulation of Au-Pyridyl Coordination Networks on Metal
Surfaces.
AB - Using scanning tunnelling microscopy (STM), we demonstrate that Au-pyridyl
coordination can be used to assemble two-dimensional coordination network
structures on metal surfaces. The polymorphism of the coordination network
structures can be manipulated at both the micro- and nanoscale. Using the same
organic ligand, we assembled two distinct polymorphic network structures, which
were assisted by threefold Au-pyridyl coordination on Ag(111) with predeposited
Au atoms (alpha-network), and by twofold Au-pyridyl coordination on Au(111) (beta
network), respectively. Specifically on the Au(111) surface, single-oriented beta
network domains as large as ~400 nm were selected by thermal annealing. We
ascribe this global control strategy to distinct Au bonding modes tuned by
molecule-substrate interactions. Using an STM tip, we succeeded in creating alpha
network domains (~10 nm) locally within the homogeneous beta-network domain areas
on Au(111) in a controlled manner.
PMID- 28513073
TI - Early neurocognitive improvements following parathyroidectomy for primary
hyperparathyroidism.
AB - OBJECTIVES: To establish a time frame for postoperative improvements in
neurocognitive function in patients who undergo parathyroidectomy for primary
hyperparathyroidism by utilizing repeat neuropsychological assessment at multiple
time points before and after surgery. STUDY DESIGN: Prospective cohort study.
METHODS: A prospective study was conducted at a tertiary academic medical center
between August 2014 and December 2015, including 50 patients with primary
hyperparathyroidism who underwent parathyroidectomy. A panel of neurocognitive
tests was administered at two separate time points: preoperative and 1-week
postoperative. Validated neuropsychological assessment tools were utilized,
including Rey Auditory-Verbal Learning Test, Trail Making Test A and B, Benton
Controlled Oral Word Association, WAIS-IV Digit Span, Hospital Anxiety and
Depression Scale, Positive and Negative Affect Schedule, and Insomnia Severity
Index. Barona Information Sheet was used to collect demographic data. Paired t
tests were to compare pre- and postoperative scores. RESULTS: Thirty-five
patients completed the preoperative and 1-week postoperative testing. In
cognitive testing, significant improvement was noted in immediate recall (P <
0.001), working memory (P = 0.011), and attention (P = 0.008) at 1-week
postoperative. In mood testing, depression (P < 0.001), anxiety (P < 0.001), and
negative affect (P = 0.001) scores were significantly improved at 1-week
postoperative. Insomnia scores also were significantly improved at 1 week (P <
0.001). CONCLUSION: Objective improvements in neurocognitive function following
parathyroidectomy for primary hyperparathyroidism were noted as early as 1 week
after surgery, which is earlier than previously reported. LEVEL OF EVIDENCE: 2b.
Laryngoscope, 128:775-780, 2018.
PMID- 28513074
TI - Delta-Myrtoxin-Mp1a is a Helical Heterodimer from the Venom of the Jack Jumper
Ant that has Antimicrobial, Membrane-Disrupting, and Nociceptive Activities.
AB - Delta-Myrtoxin-Mp1a (Mp1a), a 49-residue heterodimeric peptide from the venom of
Myrmecia pilosula, comprises a 26-mer A chain and a 23-mer B chain connected by
two disulfide bonds in an antiparallel arrangement. Combination of the individual
synthetic chains through aerial oxidation remarkably resulted in the self
assembly of Mp1a as a homogenous product without the need for directed disulfide
bond formation. NMR analysis revealed a well-defined, unique structure containing
an antiparallel alpha-helix pair. Dual polarization interferometry (DPI) analysis
showed strong interaction with supported lipid bilayers and insertion within the
bilayers. Mp1a caused non-specific Ca2+ influx in SH-SY5Y cells with a half
maximal effective concentration (EC50 ) of 4.3 MUm. Mp1a also displayed broad
spectrum antimicrobial activity, with the highest potency against Gram-negative
Acinetobacter baumannii (MIC 25 nm). Intraplantar injection (10 MUm) in mice
elicited spontaneous pain and mechanical allodynia. Single- and two-chain
mimetics of Mp1a revealed functional selectivity.
PMID- 28513075
TI - Using interpretation services during clerkships.
AB - BACKGROUND: Although using professional interpreters is known to improve health
outcomes for patients when language barriers are present, care providers often
hesitate to use them. Training in how to use interpreters has been effective in
increasing students' knowledge and self-efficacy, but little is known about how
students apply the competencies gained. We explored students' perspectives on how
they dealt with language barriers during their clerkships. METHOD: Students in
the Netherlands who received training (n = 8) and who did not receive training (n
= 8) were interviewed about their experiences during their clerkships with
regards to language barriers and the use of professional interpreters. RESULTS:
Students do not report using interpretation services during clerkships, even when
they have been trained. Students report that their supervisors and other staff
members provide barriers to the use of interpretation services. CONCLUSIONS: Not
only students but also staff need training in the use of professional
interpretation services, because staff serve as role models for the students.
Care providers often hesitate to use [professional interpreters].
PMID- 28513077
TI - Tuneable luminescence properties of EDTA-assisted ZnS:Mn nanocrystals from a
yellow-orange to a red emission band.
AB - Luminescence technology has been improved with the help of semiconductor
nanoparticles that possess novel optical and electrical properties compared with
their bulk counterpart. The aim of this study was to design semiconductor
nanocrystals in their pure (ZnS) or doped form (ZnS:Mn) with different
concentrations of Mn2+ ions by a wet chemical route stabilized by ethylenediamine
tetra-acetic acid (EDTA) and to evaluate their luminescence properties. The
nanocrystals were characterized by physicochemical techniques such as X-ray
diffraction (XRD), High-resolution transmission electron microscopy (HRTEM),
selected area electron diffraction (SEAD), EDS, and ultraviolet (UV)-visible
light and photoluminescence (PL) studies. These results showed the presence of
cubic phase and spherically shaped nanocrystals. A blue shift with respect to
their bulk counterpart was observed. PL emission spectra were observed with a
fixed blue peak and the yellow-orange bands were red shifted towards the red
region under the same excitation wavelength. The orange-red bands were attributed
to the radiation transition of electrons in 3d5 unfilled shells of Mn2+ ions [4
T1 (4 G)-6 A1 (6 S)]; the ZnS matrix varied with Mn2+ concentration. Shift and
increase in the intensity of the PL and absorption bands were observed with
increase in Mn content. The study showed that Mn2+ -doped ZnS nanocrystal
emission bands can be tuned from the yellow-orange to the red regions under a
controlled synthesis process and could be used as promising luminescent emitters
in the biology field upon functionalization with suitable materials. Further
studies on construction with various other materials will be useful for practical
applications.
PMID- 28513078
TI - Peripheral synucleinopathy in early Parkinson's disease: Submandibular gland
needle biopsy findings.
PMID- 28513076
TI - A computational assessment of the predicted structures of Human Macrophage
Migration Inhibitory Factor 1 orthologs in parasites and its affinity to human
CD74 receptor.
AB - The human macrophage migration inhibitory factor 1 (Hu-MIF-1) is a protein
involved in the inflammatory and immunology response to parasite infection. In
the present study, the existence of Hu-MIF-1 from parasites have been explored by
mining WormBase. A total of 35 helminths were found to have Hu-MIF-1 homologs,
including some parasites of importance for public health. Physicochemical,
structural, and biological properties of Hu-MIF-1 were compared with its
orthologs in parasites showing that most of these are secretory proteins, with
positive net charge and presence of the Cys-Xaa-Xaa-Cys motif that is critical
for its oxidoreductase activity. The inhibitor-binding site present in Hu-MIF-1
is well conserved among parasite MIFs suggesting that Hu-MIF inhibitors may
target orthologs in pathogens. The binding of Hu-MIF-1 to its cognate receptor
CD74 was predicted by computer-assisted docking, and it resulted to be very
similar to the predicted complexes formed by parasite MIFs and human CD74. More
than 1 plausible conformation of MIFs in the extracellular loops of CD74 may be
possible as demonstrated by the different predicted conformations of MIF
orthologs in complex with CD74. Parasite MIFs in complex with CD74 resulted with
some charged residues oriented to CD74, which was not observed in the Hu-MIF
1/CD74 complex. Our findings predict the binding mode of Hu-MIF-1 and orthologs
with CD74, which can assist in the design of novel MIF inhibitors. Whether the
parasite MIFs function specifically subvert host immune responses to suit the
parasite is an open question that needs to be further investigated. Future
research should lead to a better understanding of parasite MIF action in the
parasite biology.
PMID- 28513080
TI - Sleep Disorders and RBD: What Would James Parkinson Think?
PMID- 28513079
TI - REM Sleep Behavior Disorder in Parkinson's Disease and Other Synucleinopathies.
AB - Rapid eye movement sleep behavior disorder is characterized by dream enactment
and complex motor behaviors during rapid eye movement sleep and rapid eye
movement sleep atonia loss (rapid eye movement sleep without atonia) during
polysomnography. Rapid eye movement sleep behavior disorder may be idiopathic or
symptomatic and in both settings is highly associated with synucleinopathy
neurodegeneration, especially Parkinson's disease, dementia with Lewy bodies,
multiple system atrophy, and pure autonomic failure. Rapid eye movement sleep
behavior disorder frequently manifests years to decades prior to overt motor,
cognitive, or autonomic impairments as the presenting manifestation of
synucleinopathy, along with other subtler prodromal "soft" signs of hyposmia,
constipation, and orthostatic hypotension. Between 35% and 91.9% of patients
initially diagnosed with idiopathic rapid eye movement sleep behavior disorder at
a sleep center later develop a defined neurodegenerative disease. Less is known
about the long-term prognosis of community-dwelling younger patients, especially
women, and rapid eye movement sleep behavior disorder associated with
antidepressant medications. Patients with rapid eye movement sleep behavior
disorder are frequently prone to sleep-related injuries and should be treated to
prevent injury with either melatonin 3-12 mg or clonazepam 0.5-2.0 mg to limit
injury potential. Further evidence-based studies about rapid eye movement sleep
behavior disorder are greatly needed, both to enable accurate prognostic
prediction of end synucleinopathy phenotypes for individual patients and to
support the application of symptomatic and neuroprotective therapies. Rapid eye
movement sleep behavior disorder as a prodromal synucleinopathy represents a
defined time point at which neuroprotective therapies could potentially be
applied for the prevention of Parkinson's disease, dementia with Lewy bodies,
multiple system atrophy, and pure autonomic failure. (c) 2017 International
Parkinson and Movement Disorder Society.
PMID- 28513081
TI - Nomenclature of genetic movement disorders: Recommendations of the International
Parkinson and Movement Disorder Society task force.
PMID- 28513082
TI - Impact of Osteoarthritis on Difficulty Walking: A Population-Based Study.
AB - OBJECTIVE: To assess the relationship of hip and knee osteoarthritis (OA) to
walking difficulty. METHODS: A population cohort ages <=55 years recruited from
1996 to 1998 (n = 28,451) completed a standardized questionnaire assessing
demographics, health conditions, joint symptoms, and functional limitations,
including difficulty walking in the past 3 months. Survey data were linked to
health administrative databases; self-report and administrative data were used to
identify health conditions. Hip/knee OA was defined as self-reported swelling,
pain, or stiffness in a hip or knee lasting >=6 weeks in the past 3 months
without an inflammatory arthritis diagnosis. Using multivariable logistic
regression, we examined the determinants of walking difficulty and constructed a
clinical nomogram. RESULTS: A total of 18,490 cohort participants were eligible
(mean age 68 years, 60% women), and 25% reported difficulty walking. Difficulty
walking was significantly and independently associated with older age, female
sex, body mass index, and several health conditions. Of the conditions examined,
the likelihood of walking difficulty was greatest with hip and knee OA and
increased with the number of hip/knee joints affected. The predicted probability
of difficulty walking for a 60-year-old middle-income, normal-weight woman was 5
10% with no health conditions, 10-20% with diabetes mellitus and cardiovascular
(CV) disease, 40% with OA in 2 hips/knees, 60-70% with diabetes mellitus, CV
disease, and OA in 2 hips/knees, and 80% with diabetes mellitus, CV disease, and
OA in all hips/knees. CONCLUSION: In a population cohort, symptomatic hip/knee OA
was the strongest contributor to walking difficulty. Given the importance of
walking to engagement in physical activity for chronic disease management,
greater attention to OA is warranted.
PMID- 28513084
TI - Exploring the role of occupational therapy in caring for cancer survivors in
Australia: A cross sectional study.
AB - BACKGROUND/AIM: With increasing rates of cancer survival in Australia, more
people are living with long-term side effects of cancer and its treatment, and
cancer survivorship is now considered a distinct phase of cancer care. While
occupational therapists play an integral role in multidisciplinary care for
people with chronic conditions, there is little evidence documenting the
occupational therapy role for people living with chronic cancer-related
conditions. This study aimed to explore the views of Australian occupational
therapists about current practice and what constitutes best practice for cancer
survivors. METHODS: A cross-sectional online survey was developed and distributed
via emailed invitations to the Occupational Therapy Australia membership to
collect responses from occupational therapists in a range of locations and
practice settings around Australia. RESULTS: A total of 204 completed surveys
were returned (response rate of 4%). More than 70% (n = 143) of respondents
worked with people with cancer at least sometimes and most worked in acute
(13.8%, n = 28) or community (11.2%, n = 23) settings. Participants rated
equipment provision as the most common intervention (94%, n = 192), followed by
energy conservation (91%, n = 185) and pressure care (78%, n = 160). Lack of
funding for occupational therapy positions and a lack of recognition of the role
of occupational therapy by health professionals and consumers were identified as
key barriers to survivorship care. CONCLUSION: Research is needed to provide
evidence supporting the role and practice of occupational therapy with cancer
survivors. Collaborative work with multidisciplinary teams is needed to develop
long-term routine treatment pathways that include occupational therapy
interventions.
PMID- 28513083
TI - Screen-printed ambulatory electrode set enables accurate diagnostics of sleep
bruxism.
AB - Currently, definite diagnosis of sleep bruxism requires polysomnography. However,
it is restrictedly available, and too cumbersome and expensive for the purpose.
The aim of this study was to introduce an ambulatory electrode set and evaluate
its feasibility for more cost-effective diagnostics of sleep bruxism. Six self
assessed bruxers (one male, five females; aged 21-58 years) and six healthy
controls (four males, two females, aged 21-25 years) underwent a standard
polysomnographic study and a concurrent study with the ambulatory electrode set.
Bruxism events, cortical arousals and sleep stages were scored for the two
montages separately in a random order, and obtained sleep parameters were
compared. In addition, the significance of video recording and sleep stage
scoring for the diagnostic accuracy of ambulatory electrode set was determined.
Ambulatory electrode set yielded similar diagnoses as standard polysomnography in
all subjects. However, compared with standard polysomnography the median
(interquartile range) tonic bruxism event index was significantly higher in the
control group [+0.38 (+0.08 to +0.56) events per hour, P = 0.046], and the phasic
bruxism event index was significantly lower in the bruxer group [-0.44 (-1.30 to
+0.07) events per hour, P = 0.046]. Exclusion of video recording and both video
recording and sleep stage scoring from analysis increased overestimation of the
tonic bruxism event index in the control group +0.86 (+0.42 to +1.03) and +1.19
(+0.55 to +1.39) events per hour, P = 0.046 and P = 0.028, respectively],
resulting in one misdiagnosed control subject. To conclude, ambulatory electrode
set is a sensitive method for ambulatory diagnostics of sleep bruxism, and video
recording and sleep stage scoring help reaching the highest specificity of sleep
bruxism diagnostics.
PMID- 28513085
TI - Systematic review with meta-analysis: endoscopic dilation is highly effective and
safe in children and adults with eosinophilic oesophagitis.
AB - BACKGROUND: Oesophageal dilation is frequently used as an adjunct treatment to
alleviate symptoms that develop from fibrostenotic remodelling in eosinophilic
oesophagitis (EoE). Earlier reports described an increased risk of complications
associated with dilation. AIM: Perform a systematic review and meta-analysis to
assess the efficacy and safety of endoscopic dilation in children and adults with
EoE. METHODS: Professional librarians searched MEDLINE, EMBASE, the Cochrane
library, Scopus, and Web of Science for articles in any language describing
studies of dilation in EoE through December 2016. Studies were selected and data
were abstracted independently and in duplicate. Random effects modelling was used
to generate summary estimates for clinical improvement and complications
(haemorrhage, perforation, hospitalisation, and death). RESULTS: The search
resulted in 3495 references, of which 27 studies were included in the final
analysis. The studies described 845 EoE patients, including 87 paediatric
patients, who underwent a total of 1820 oesophageal dilations. The median number
of dilations was 3 (range: 1-35). Clinical improvement occurred in 95% of
patients (95% CI: 90%-98%, I2 : 10%, 17 studies). Perforation occurred in 0.38%
(95% CI: 0.18%-0.85%, I2 : 0%, 27 studies), haemorrhage in 0.05% (95% CI: 0%
0.3%, I2 : 0%, 18 studies), and hospitalisation in 0.67% (95% CI: 0.3%-1.1%, I2 :
44%, 24 studies). No deaths occurred (95% CI: 0%-0.2% I2 : 0%, 25 studies).
CONCLUSIONS: Endoscopic dilation is consistently effective in children and adults
with EoE, resulting in improvement in 95% of patients with very low rates (<1%)
of major complications.
PMID- 28513086
TI - Photoluminescent properties of novel design heteroleptic Zn(II) complexes.
AB - Three novel heteroleptic Zn(II) complexes containing 8-hydroxy quinoline and
various pyrazolone-based derivatives were synthesized and their structures
confirmed by 1 H-nuclear magnetic resonance, mass spectrometry, Fourier transform
infra-red spectroscopy, UV-vis analysis and element analysis. All three complexes
showed good photoluminescence properties in the solid state and in solution in
the maximum emission range from 475 to 490 nm with a quantum yield of 0.45 to
0.51. Absorption spectra revealed that the complexes possessed a maximum
absorption range of 272-281 nm with a band gap of 2.59-2.68 eV. The highest
occupied molecular orbital and lowest unoccupied molecular orbital of all the
complexes were determine by cyclic voltammetry. All complexes displayed high
thermal stability. These characteristics were assessed to find suitability for an
alternative cheap light emitter for organic light-emitting diodes.
PMID- 28513087
TI - Kangaroo mother care to reduce morbidity and mortality in low birth weight
infants.
PMID- 28513089
TI - Editorial overview: Celebrating the advances in cell biology from China.
PMID- 28513088
TI - Psoas muscle area is not representative of total skeletal muscle area in the
assessment of sarcopenia in ovarian cancer.
AB - BACKGROUND: Computed tomography measurements of total skeletal muscle area can
detect changes and predict overall survival (OS) in patients with advanced
ovarian cancer. This study investigates whether assessment of psoas muscle area
reflects total muscle area and can be used to assess sarcopenia in ovarian cancer
patients. METHODS: Ovarian cancer patients (n = 150) treated with induction
chemotherapy and interval debulking were enrolled retrospectively in this
longitudinal study. Muscle was measured cross sectionally with computed
tomography in three ways: (i) software quantification of total skeletal muscle
area (SMA); (ii) software quantification of psoas muscle area (PA); and (iii)
manual measurement of length and width of the psoas muscle to derive the psoas
surface area (PLW). Pearson correlation between the different methods was
studied. Patients were divided into two groups based on the extent of change in
muscle area, and agreement was measured with kappa coefficients. Cox-regression
was used to test predictors for OS. RESULTS: Correlation between SMA and both
psoas muscle area measurements was poor (r = 0.52 and 0.39 for PA and PLW,
respectively). After categorizing patients into muscle loss or gain, kappa
agreement was also poor for all comparisons (all kappa < 0.40). In regression
analysis, SMA loss was predictive of poor OS (hazard ratio 1.698 (95%CI 1.038
2.778), P = 0.035). No relationship with OS was seen for PA or PLW loss.
CONCLUSIONS: Change in psoas muscle area is not representative of total muscle
area change and should not be used to substitute total skeletal muscle to predict
survival in patients with ovarian cancer.
PMID- 28513090
TI - Benchmarking a computational design method for the incorporation of metal ion
binding sites at symmetric protein interfaces.
AB - The design of novel metal-ion binding sites along symmetric axes in protein
oligomers could provide new avenues for metalloenzyme design, construction of
protein-based nanomaterials and novel ion transport systems. Here, we describe a
computational design method, symmetric protein recursive ion-cofactor sampling
(SyPRIS), for locating constellations of backbone positions within oligomeric
protein structures that are capable of supporting desired symmetrically
coordinated metal ion(s) chelated by sidechains (chelant model). Using SyPRIS on
a curated benchmark set of protein structures with symmetric metal binding sites,
we found high recovery of native metal coordinating rotamers: in 65 of the 67
(97.0%) cases, native rotamers featured in the best scoring model while in the
remaining cases native rotamers were found within the top three scoring models.
In a second test, chelant models were crossmatched against protein structures
with identical cyclic symmetry. In addition to recovering all native placements,
10.4% (8939/86013) of the non-native placements, had acceptable geometric
compatibility scores. Discrimination between native and non-native metal site
placements was further enhanced upon constrained energy minimization using the
Rosetta energy function. Upon sequence design of the surrounding first-shell
residues, we found further stabilization of native placements and a small but
significant (1.7%) number of non-native placement-based sites with favorable
Rosetta energies, indicating their designability in existing protein interfaces.
The generality of the SyPRIS approach allows design of novel symmetric metal
sites including with non-natural amino acid sidechains, and should enable the
predictive incorporation of a variety of metal-containing cofactors at symmetric
protein interfaces.
PMID- 28513091
TI - Estimation of exposure distribution adjusting for association between exposure
level and detection limit.
AB - In environmental exposure studies, it is common to observe a portion of exposure
measurements to fall below experimentally determined detection limits (DLs). The
reverse Kaplan-Meier estimator, which mimics the well-known Kaplan-Meier
estimator for right-censored survival data with the scale reversed, has been
recommended for estimating the exposure distribution for the data subject to DLs
because it does not require any distributional assumption. However, the reverse
Kaplan-Meier estimator requires the independence assumption between the exposure
level and DL and can lead to biased results when this assumption is violated. We
propose a kernel-smoothed nonparametric estimator for the exposure distribution
without imposing any independence assumption between the exposure level and DL.
We show that the proposed estimator is consistent and asymptotically normal.
Simulation studies demonstrate that the proposed estimator performs well in
practical situations. A colon cancer study is provided for illustration.
Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28513092
TI - Pharmacokinetics and pharmacodynamics of meldonium in exercised thoroughbred
horses.
AB - Although developed as a therapeutic medication, meldonium has found widespread
use in human sports and was recently added to the World Anti-Doping Agency's list
of prohibited substances. Its reported abuse potential in human sports has led to
concern by regulatory authorities about the possible misuse of meldonium in
equine athletics. The potential abuse in equine athletes along with the limited
data available regarding the pharmacokinetics and pharmacodynamics of meldonium
in horses necessitates further study. Eight exercised adult thoroughbred horses
received a single oral dose of 3.5, 7.1, 14.3 or 21.4 mg/kg of meldonium. Blood
and urine samples were collected and analyzed using liquid chromatography tandem
mass spectrometry. Pharmacokinetic parameters were determined using non
compartmental analysis. Maximum serum concentrations ranged from 440.2 to 1147
ng/mL and the elimination half-life from 422 to 647.8 h. Serum concentrations
were below the limit of quantitation by days 4, 7, 12 and 12 for doses of 3.5,
7.1, 14.3 and 21.4 mg/kg, respectively. Urine concentrations were below the limit
of detection by day 44 following administration of 3.5 mg/kg and day 51 for all
other dose groups. No adverse effects were observed following meldonium
administration. While the group numbers were small, changes in heart rate were
observed in the 3.5 mg/kg dose group (n = 1). Glucose concentrations changed
significantly in all dose groups studied (n = 2 per dose group). Similar to that
reported for humans, the detection time of meldonium in biological samples
collected from horses is prolonged, which should allow for satisfactory
regulation in performance horses. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28513093
TI - Treatment and outcomes of patients presenting to an adult emergency department
involuntarily with substance misuse.
AB - Alcohol and other drug (AOD) use is common in our society. The use of these
substances flow throughout all areas of healthcare, and is especially prevalent
in patients presenting to the emergency department with signs of mental illness.
At the extreme end of these presentations patients present involuntarily with
either police or ambulance officers. The aim of this study was to identify and
describe the population presenting to the ED involuntarily with and without
substance misuse as a precipitating factor. Quantitative descriptive analysis was
used to describe this population between April and June 2015. In patients
presenting to one large inner city emergency department involuntarily, 30% had
alcohol or other drug misuse as a precipitating factor. Patients who
involuntarily presented with alcohol and other misuse stay longer in the
emergency department then others that do not have alcohol or other drug misuse.
These patients represent frequently, with over 50% representing at 90 days
however this was not associated with alcohol or other drug misuse. Almost all
patients who present involuntarily are discharged home post review by a mental
health team. Significant improvements in care can be made in this population if
the opportunistic treatment of both mental illness and AOD misuse is completed in
the emergency department.
PMID- 28513094
TI - Chemiluminescence detection of trace iodide with flow injection analysis of KMnO4
-carbon dots system.
AB - Ultra-weak chemiluminescence (CL) from the reaction of iodide and KMnO4 was
strongly enhanced by carbon nanodots (CNDs) in an acidic medium. The CL intensity
was directly proportional to the concentration of iodide in the solution.
Therefore, a flow-injection CL system with high sensitivity, selectivity and
reproducibility is proposed for the determination of iodide. The proposed method
exhibited advantages over a linear range of 3.0 * 10-6 -1.0 * 10-4 mol/L and had
a detection limit of 3.5 * 10-7 mol/L. The method was successfully applied to
the evaluation of iodide in food samples with recoveries of between 96 and 103%.
The relative standard deviations were 2.1 and 4.1% for intra- and inter-assay
precision, respectively.
PMID- 28513095
TI - Research of the master-slave robot surgical system with the function of force
feedback.
AB - BACKGROUND: Surgical robots lack force feedback, which may lead to operation
errors. In order to improve surgical outcomes, this research developed a new
master-slave surgical robot, which was designed with an integrated force sensor.
METHODS: The new structure designed for the master-slave robot employs a force
feedback mechanism. A six-dimensional force sensor was mounted on the tip of the
slave robot's actuator. Sliding model control was adopted to control the slave
robot. According to the movement of the master system manipulated by the surgeon,
the slave's movement and the force feedback function were validated. RESULTS: The
motion was completed, the standard deviation was calculated, and the force data
were detected. Hence, force feedback was realized in the experiment. CONCLUSIONS:
The surgical robot can help surgeons to complete trajectory motions with haptic
sensation.
PMID- 28513096
TI - Is the oral fungal pathogen Candida albicans a cariogen?
AB - Pathobiology of dental caries is complex. Data from recent molecular
microbiologic studies have further redefined the role of the oral microbiome in
the etiology of dental caries. This new information challenges the conventional
view on the hegemony of classic cariogenic prokaryotes such as Streptococcus
mutans in caries etiology, and raises the intriguing possibility of the
participation of the eukaryotic oral fungal pathogen Candida in the caries
process. The virulence attributes of Candida species such as their acidogenicity
and aciduric nature, the ability to develop profuse biofilms, ferment and
assimilate dietary sugars, and produce collagenolytic proteinases are all
indicative of their latent cariogenic potential. Based on the above, oral
candidal counts have been used by some as a caries risk indicator. On the
contrary, other studies suggest that Candida is merely a passenger extant in an
acidic cariogenic milieu, and not a true pathogen. In this review, we critically
examine the varying roles of Candida, and traditionally accepted cariogens such
as the mutans group of streptococci in the pathobiology of dental caries. The
weight of available data tends to imply that Candida may play a pivotal role as a
secondary agent perpetuating the carious process, especially in dentinal caries.
PMID- 28513098
TI - Non-alcoholic fatty liver disease and type 2 diabetes: Importance of glycemic
control.
PMID- 28513097
TI - Evidence for a peptidoglycan-like structure in Orientia tsutsugamushi.
AB - Bacterial cell walls are composed of the large cross-linked macromolecule
peptidoglycan, which maintains cell shape and is responsible for resisting
osmotic stresses. This is a highly conserved structure and the target of numerous
antibiotics. Obligate intracellular bacteria are an unusual group of organisms
that have evolved to replicate exclusively within the cytoplasm or vacuole of a
eukaryotic cell. They tend to have reduced amounts of peptidoglycan, likely due
to the fact that their growth and division takes place within an osmotically
protected environment, and also due to a drive to reduce activation of the host
immune response. Of the two major groups of obligate intracellular bacteria, the
cell wall has been much more extensively studied in the Chlamydiales than the
Rickettsiales. Here, we present the first detailed analysis of the cell envelope
of an important but neglected member of the Rickettsiales, Orientia
tsutsugamushi. This bacterium was previously reported to completely lack
peptidoglycan, but here we present evidence supporting the existence of a
peptidoglycan-like structure in Orientia, as well as an outer membrane containing
a network of cross-linked proteins, which together confer cell envelope
stability. We find striking similarities to the unrelated Chlamydiales,
suggesting convergent adaptation to an obligate intracellular lifestyle.
PMID- 28513099
TI - Syntheses, analytical and pharmacological characterizations of the 'legal high' 4
[1-(3-methoxyphenyl)cyclohexyl]morpholine (3-MeO-PCMo) and analogues.
AB - New psychoactive substances (NPS) are commonly referred to as 'research
chemicals', 'designer drugs' or 'legal highs'. One NPS class is represented by
dissociative anesthetics, which include analogues of the arylcyclohexylamine
phencyclidine (PCP), ketamine and diphenidine. A recent addition to the NPS
market was 4-[1-(3-methoxyphenyl)cyclohexyl]morpholine (3-MeO-PCMo), a morpholine
analogue of 3-MeO-PCP. Although suspected to have dissociative effects in users,
information about its pharmacological profile is not available. From clinical and
forensic perspectives, detailed analytical data are needed for identification,
especially when facing the presence of positional isomers, as these are
frequently unavailable commercially. This study presents the analytical and
pharmacological characterization of 3-MeO-PCMo along with five additional
analogues, namely the 2- and 4-MeO-PCMo isomers, 3,4-methylenedioxy-PCMo (3,4-MD
PCMo), 3-Me-PCMo and PCMo. All six arylcyclohexylmorpholines were synthesized and
characterized using chromatographic, mass spectrometric and spectroscopic
techniques. The three positional isomers could be differentiated and the identity
of 3-MeO-PCMo obtained from an internet vendor was verified. All six compounds
were also evaluated for affinity at 46 central nervous system receptors including
the N-methyl-d-aspartate receptor (NMDAR), an important target for dissociative
anesthetics such as PCP and ketamine. In vitro binding studies using (+)-[3-3 H]
MK-801 in rat forebrain preparations revealed moderate affinity for NMDAR in the
rank order of 3-Me >3-MeO > PCMo >3,4-MD > 2-MeO > 4-MeO-PCMo. 3-MeO-PCMo was
found to have moderate affinity for NMDAR comparable to that of ketamine, and had
an approximate 12-fold lower affinity than PCP. These results support the
anecdotal reports of dissociative effects from 3-MeO-PCMo in humans.
PMID- 28513100
TI - Function of bacteriophage G7C esterase tailspike in host cell adsorption.
AB - Bacteriophages recognize and bind to their hosts with the help of receptor
binding proteins (RBPs) that emanate from the phage particle in the form of
fibers or tailspikes. RBPs show a great variability in their shapes, sizes, and
location on the particle. Some RBPs are known to depolymerize surface
polysaccharides of the host while others show no enzymatic activity. Here we
report that both RBPs of podovirus G7C - tailspikes gp63.1 and gp66 - are
essential for infection of its natural host bacterium E. coli 4s that populates
the equine intestinal tract. We characterize the structure and function of gp63.1
and show that unlike any previously described RPB, gp63.1 deacetylates surface
polysaccharides of E. coli 4s leaving the backbone of the polysaccharide intact.
We demonstrate that gp63.1 and gp66 form a stable complex, in which the N
terminal part of gp66 serves as an attachment site for gp63.1 and anchors the
gp63.1-gp66 complex to the G7C tail. The esterase domain of gp63.1 as well as
domains mediating the gp63.1-gp66 interaction is widespread among all three
families of tailed bacteriophages.
PMID- 28513101
TI - Industrialization of a perfusion bioreactor: Prime example of a non
straightforward process.
AB - Bioreactors are essential enabling technologies for the translation of advanced
therapies medicinal products from the research field towards a successful
clinical application. In order to speed up the translation and the spread of
novel tissue engineering products into the clinical routine, tissue engineering
bioreactors should evolve from laboratory prototypes towards industrialized
products. In this work, we thus challenged the industrialization process of a
novel technological platform, based on an established research prototype of
perfusion bioreactor, following a GMP-driven approach. We describe how the
combination of scientific background, intellectual property, start-up factory
environment, wise industrial advice in the biomedical field, design, and
regulatory consultancy allowed us to turn a previously validated prototype
technology into an industrial product suitable for serial production with
improved replicability and user-friendliness. The solutions implemented enhanced
aesthetics, ergonomics, handling, and safety of the bioreactor, and they allowed
compliance with the fundamental requirements in terms of traceability,
reproducibility, efficiency, and safety of the manufacturing process of advanced
therapies medicinal products. The result is an automated incubator-compatible
device, housing 12 disposable independent perfusion chambers for seeding and
culture of any perfusable tissue. We validated the cell seeding process of the
industrialized bioreactor by means of the Design of Experiment approach, whilst
the effectiveness of perfusion culture was evaluated in the context of bone
tissue engineering.
PMID- 28513103
TI - A systematic review and meta-analysis of interval training versus moderate
intensity continuous training on body adiposity.
AB - Interval training (including high-intensity interval training [HIIT] and sprint
interval training [SIT]) is promoted in both scientific and lay media as being a
superior and time-efficient method for fat loss compared with traditional
moderate-intensity continuous training (MICT). We evaluated the efficacy of
HIIT/SIT when directly compared with MICT for the modulation of body adiposity.
Databases were searched to 31 August 2016 for studies with exercise training
interventions with minimum 4-week duration. Meta-analyses were conducted for
within-group and between-group comparisons for total body fat percentage (%) and
fat mass (kg). To investigate heterogeneity, we conducted sensitivity and meta
regression analyses. Of the 6,074 studies netted, 31 were included. Within-group
analyses demonstrated reductions in total body fat (%) (HIIT/SIT: -1.26 [95% CI:
1.80; -0.72] and MICT: -1.48 [95% CI: -1.89; -1.06]) and fat mass (kg) (HIIT/SIT:
-1.38 [95% CI: -1.99; -0.77] and MICT: -0.91 [95% CI: -1.45; -0.37]). There were
no differences between HIIT/SIT and MICT for any body fat outcome. Analyses
comparing MICT with HIIT/SIT protocols of lower time commitment and/or energy
expenditure tended to favour MICT for total body fat reduction (p = 0.09).
HIIT/SIT appears to provide similar benefits to MICT for body fat reduction,
although not necessarily in a more time-efficient manner. However, neither short
term HIIT/SIT nor MICT produced clinically meaningful reductions in body fat.
PMID- 28513102
TI - How bilingualism protects the brain from aging: Insights from bimodal bilinguals.
AB - Bilingual experience can delay cognitive decline during aging. A general
hypothesis is that the executive control system of bilinguals faces an increased
load due to controlling two languages, and this increased load results in a more
"tuned brain" that eventually creates a neural reserve. Here we explored whether
such a neuroprotective effect is independent of language modality, i.e., not
limited to bilinguals who speak two languages but also occurs for bilinguals who
use a spoken and a signed language. We addressed this issue by comparing bimodal
bilinguals to monolinguals in order to detect age-induced structural brain
changes and to determine whether we can detect the same beneficial effects on
brain structure, in terms of preservation of gray matter volume (GMV), for
bimodal bilinguals as has been reported for unimodal bilinguals. Our GMV analyses
revealed a significant interaction effect of age * group in the bilateral
anterior temporal lobes, left hippocampus/amygdala, and left insula where bimodal
bilinguals showed slight GMV increases while monolinguals showed significant age
induced GMV decreases. We further found through cortical surface-based
measurements that this effect was present for surface area and not for cortical
thickness. Moreover, to further explore the hypothesis that overall bilingualism
provides neuroprotection, we carried out a direct comparison of GMV, extracted
from the brain regions reported above, between bimodal bilinguals, unimodal
bilinguals, and monolinguals. Bilinguals, regardless of language modality,
exhibited higher GMV compared to monolinguals. This finding highlights the
general beneficial effects provided by experience handling two language systems,
whether signed or spoken. Hum Brain Mapp 38:4109-4124, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28513104
TI - Novelty seeking and reward dependence-related large-scale brain networks
functional connectivity variation during salience expectancy.
AB - A salience network (SN) anchored in the anterior insula (AI) and dorsal anterior
cingulate cortex (dACC) plays a key role in switching between brain networks
during salience detection and attention regulation. Previous fMRI studies have
associated expectancy behaviors and SN activation with novelty seeking (NS) and
reward dependence (RD) personality traits. To address the question of how
functional connectivity (FC) in the SN is modulated by internal (expectancy
related) salience assignment and different personality traits, 68 healthy
participants performed a salience expectancy task using functional magnetic
resonance imaging, and psychophysiological interaction analysis (PPI) was
conducted to determine salience-related connectivity changes during these
anticipation periods. Correlation was then evaluated between PPI and personality
traits, assessed using the temperament and character inventory of 32 male
participants. During high salience expectancy, SN-seed regions showed reduced FC
to visual areas and parts of the default mode network, but increased FC to the
central executive network. With increasing NS, participants showed significantly
increasing disconnection between right AI and middle cingulate cortex when
expecting high-salience pictures as compared to low-salience pictures, while
increased RD also predicted decreased right dACC and caudate FC for high salience
expectancy. Our findings suggest a direct link between personality traits and
internal salience processing mediated by differential network integration of the
SN. SN activity and coordination may therefore be moderated by novelty seeking
and reward dependency personality traits, which are associated with risk of
addiction. Hum Brain Mapp 38:4064-4077, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28513106
TI - Cholecystitis in situs inversus totalis.
PMID- 28513107
TI - Extramedullary leukaemia presenting as cardiac myeloid sarcoma.
PMID- 28513105
TI - Hair follicle specific ACVR1/ALK2 critically affects skin morphogenesis and
attenuates wound healing.
AB - The bone morphogenic protein signaling (BMP) is intricately involved in the
quiescence and regulation of stem cells through activation of BMP receptors. Hair
follicle stem cells play a critical role in cutaneous homeostasis and
regeneration. Here, we utilize a novel mouse model with targeted overexpression
of the BMP receptor ALK2/ACVR1 in hair follicle stem cells, to characterize its
role in skin development and postnatal wound healing. Initial histologic
evaluation demonstrated significant dysregulation in hair follicle morphogenesis
in mutant mice. These demonstrated increased numbers of individual hair follicles
with altered morphology and localization. Mutant follicles were found to exhibit
elevated proliferative activity as well as increased prevalence of CD34 and ITGA6
positive follicle stem cells. Interestingly, constitutive overexpression of ALK2
resulted in attenuation of cutaneous wound healing. These findings demonstrate
that hair follicle specific ALK2 is intricately involved in maintenance of the
stem cell niche and wound healing.
PMID- 28513108
TI - Dermatofibrosarcoma protuberans of the scalp: therapeutic challenges.
PMID- 28513109
TI - Separation and identification of mouse brain tissue microproteins using top-down
method with high resolution nanocapillary liquid chromatography mass
spectrometry.
AB - Microproteins and endogenous peptides in the brain contain important substances
that have critical roles in diverse biological processes, contributing to signal
transduction and intercellular signaling. However, variability in their physical
or chemical characteristics, such as molecule size, hydrophobicity, and charge
states, complicate the simultaneous analysis of these compounds, although this
would be highly beneficial for the field of neuroscience research. Here, we
present a top-down analytical method for simultaneous analysis of microproteins
and endogenous peptides using high-resolution nanocapillary LC-MS/MS. This method
is detergent-free and digestion-free, which allows for extracting and preserving
intact microproteins and peptides for direct LC-MS analysis. Both higher energy
collision dissociation and electron-transfer dissociation fragmentations were
used in the LC-MS analysis to increase the identification rate, and
bioinformatics tools ProteinGoggle and PEAKS Studio software were utilized for
database search. In total, we identified 471 microproteins containing 736
proteoforms, including brain-derived neurotrophic factor and a number of
fibroblast growth factors. In addition, we identified 599 peptides containing 151
known or potential neuropeptides such as somatostatin-28 and neuropeptide Y. Our
approach bridges the gap for the characterization of brain microproteins and
peptides, which permits quantification of a diversity of signaling molecules for
biomarker discovery or therapy diagnosis in the future.
PMID- 28513111
TI - Type 2 Diabetic Patients Fasting on Ramadan in Israel.
AB - BACKGROUND: Fasting during Ramadan is not mandatory for diabetic patients, but
the majority of type 2 diabetic patients insist on fasting despite the potential
risks. These patients represent a challenge not only for themselves, but also for
healthcare practitioners during this period. This review provides, for the first
time, healthcare practitioners in Israel with guidelines and recommendations that
fit the Muslim population for better management of diabetic patients who fast
during Ramadan, taking into consideration recently published recommendations and
therapies available in Israel.
PMID- 28513110
TI - Separation and purification of two minor typical diarrhetic shellfish poisoning
toxins from harmful marine microalgae via combined liquid chromatography with
mass spectrometric detection.
AB - A novel method was developed for the purification of two typical diarrhetic
shellfish poisoning toxins from toxin-producing marine microalgae using
macroporous resin, high-speed countercurrent chromatography-mass spectrometry,
and semipreparative high-performance liquid chromatography-mass spectrometry.
Analytical high-performance liquid chromatography-mass spectrometry was used for
identification and purity analysis of okadaic acid and dinophysistoxin-1 because
they exhibit no visible or ultraviolet absorption. First, four kinds of
macroporous resins were investigated, and HP-20 macroporous resin was selected
for the preenrichment and cleanup of the two target toxins. Second, the resin
purified sample was further purified using high-speed countercurrent
chromatography coupled with a mass spectrometer. The purities of the obtained
okadaic acid and dinophysistoxin-1 were 89.0 and 83.0%, respectively, as
determined through analytical high-performance liquid chromatography-mass
spectrometry. Finally, further purification was carried out using semipreparative
high-performance liquid chromatography with mass spectrometry, and the purities
of the final okadaic acid and dinophysistoxin-1 products were both over 98.0%
based on the analytical high-performance liquid chromatography-mass spectrometry
chromatograms and fraction spectra. This work demonstrates that the proposed
purification process is a powerful method for the preparation of high-purity
okadaic acid and dinophysistoxin-1 from toxin-producing marine microalgae.
Moreover, it is particularly important for the purification and preparation of
minor toxins that exhibit no visible or ultraviolet absorption from harmful
marine algae.
PMID- 28513112
TI - Risk of Overweight in Adolescence among Offspring of Diabetic Mothers.
PMID- 28513113
TI - Retina and Nerve Fiber Layer Thickness in Eyes with Thyroid-Associated
Ophthalmopathy.
AB - BACKGROUND: Thyroid-associated ophthalmopathy (TAO) is an inflammatory disease
that affects the thyroid gland and the eye orbit. Of patients with TAO, 3%-5%
have severe sight-threatening disease due to optic neuropathy Optical coherence
tomography (OCT), the non-invasive imaging technology that yields high-resolution
cross-sectional images of the retina, provides qualitative and quantitative data
on the retina. OBJECTIVES: To apply this technique to quantitatively assess
retinal nerve fiber layer (RNFL) and macular ring thicknesses in healthy subjects
and in patients with TAO to determine their relationship to the severity of the
orbital disease. METHODS: All patients in the ophthalmology clinic who were
diagnosed with TAO and underwent OCT imaging as part of their ocular examination
comprised the study group, and healthy patients who volunteered to undergo OCT
examination served as controls. Results of the complete ophthalmologic
examination and OCT findings were collected from medical files, including the
thickness of the RNFL and the macula. RESULTS: The study comprised 21 patients
and 41 healthy controls. TAO patients exhibited RNFL thickening and inner macula
thinning compared to healthy subjects. Mean RNFL thickness was correlated with
the severity of the orbital disease. CONCLUSIONS: The OCT findings suggest that
the retina is involved in TAO, probably as early as the subclinical stage. This
highlights the ability of OCT to identify retinal changes earlier and far more
accurately than is detected today, enabling earlier diagnosis and more timely
treatment to prevent severe visual sequelae.
PMID- 28513114
TI - When Cardioversion May Be Complicated.
AB - BACKGROUND: In recent years cardioversion of atrial fibrillation has become a
routine procedure, enabling symptomatic functional improvement in most cases.
However, some patients develop complications after cardioversion. Identifying
these individuals is an important step toward improving patient outcome.
OBJECTIVES: To characterize those patients who may not benefit from cardioversion
or who may develop complications following cardioversion. METHODS: We
retrospectively analyzed 186 episodes of cardioversion in 163 patients with
atrial fibrillation who were admitted to our cardiology department between 2008
and 2013 based on their clinical and echocardiographic data. Patients were
divided into two groups: those with uncomplicated cardioversion, and those who
developed complications after cardioversion. RESULTS: Of the 186 episodes,
cardioversion was done in 112 men (60%) and 74 women (40%), P < 0.00001.
Complications after cardioversion occurred in 25 patients (13%). These patients
were generally older (72 vs. 65 years, P < 0.01), were more often diabetic (52%
vs. 27%, P = 0.005), had undergone emergency cardioversion (64% vs. 40%, P =
0.01), had left ventricular hypertrophy (left ventricular mass 260 vs. 218 g, P =
0.01), had larger left atrium (left atrial volume 128 vs. 102 ml, P < 0.009), and
more often died from complications of cardioversion (48% vs. 16%). They had
significant mitral regurgitation (20% vs. 4%, P = 0.03) and higher pulmonary
artery pressure (50 vs. 42 mm Hg, P < 0.02). CONCLUSIONS: People with
complications after cardioversion tend to be older, are more often diabetic and
more often have severe mitral regurgitation. In these patients, the decision to
perform cardioversion should consider the possibility of complications.
PMID- 28513115
TI - Endarterectomy or Stenting in Severe Asymptomatic Carotid Stenosis.
AB - BACKGROUND: Stroke is a major cause of death in the western world, and carotid
endarterectomy has been shown to be effective in treating both symptomatic and
asymptomatic carotid stenosis. Carotid stenting is a relatively new form of
treatment for carotid stenosis and few studies have looked specifically at
asymptomatic patients. OBJECTIVES: To retrospectively examine short- and long
term results in the treatment of asymptomatic carotid artery stenosis with
surgery or stenting. METHODS: We retrospectively collected data of all patients
with asymptomatic carotid stenosis treated by carotid artery stenting or carotid
endarterectomy in our department from 2006-2007. The primary endpoints were
stroke, myocardial infarction, or death during the periprocedural period; or any
ipsilateral stroke, restenosis, or death within 4 years after the procedure.
RESULTS: The study comprised 409 patients who were treated by either stenting or
surgery. There was a low morbidity rate in both treatment groups with no
significant difference in morbidity or mortality between the treatment groups in
both in the short-term as well as long-term. CONCLUSIONS: Both treatment methods
have a low morbidity and mortality rate and should be considered for patients
with few risk factors and a long life expectancy. Treatment method should be
selected according to the patient's individual risk factors and imaging data.
PMID- 28513116
TI - Worse Outcome in Patients with Acute Stroke and Atrial Fibrillation Following
Thrombolysis.
AB - BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia and a common
cause of ischemic stroke. Stroke patients with AF have been shown to have a
poorer neurological outcome than stroke patients without AF. OBJECTIVES: To
determine the impact of pre-existing AF on residual degree of disability in
patients treated with IV thrombolysis. METHODS: In this case-control study, data
of 214 stroke patients (63 with AF and 151 without AF) were collected from the
National Acute Stroke Israeli Registry, a nationwide quadrennial stroke database.
Stroke severity and outcome were compared using the National Institute of Health
Stroke Scale (NIHSS) on admission and the modified Rankin Scale (mRS) on
admission and discharge. Demographics and stroke characteristics were also
compared between the groups. RESULTS: Stroke severity, as determined by NIHSS at
admission, was higher in the AF group than the non-AF. In the group of patients
who were treated with intravenous tissue plasminogen activator (tPA), more
patients had favorable outcomes (mRS = 0-1 on discharge) in the non-AF group than
in the AF group (P = 0.058, odds ratio = 2.217, confidence interval 0.973 to
5.05). CONCLUSIONS: Our study suggests worse outcome in thrombolized patients
with AF compared to non-AF stroke patients. Therefore, AF itself can be a poor
prognostic factor for tPA sensitivity regarding the chance of revascularization
and recovery after intravenous tPA.
PMID- 28513117
TI - Routine Laboratory Indices as Predictor of Neurological Recovery in Post
Resuscitation Syndrome Patients Treated with Therapeutic Hypothermia.
AB - BACKGROUND: Hypothermia is associated with improved outcome in selected survivors
of cardiac arrest but no single metric enables proper prediction of neurological
outcome. OBJECTIVES: To explored the association between routine laboratory
indices of patients treated by hypothermia for cardiac arrest and their
neurological outcome. METHODS: We retrospectively collected data from survivors
of cardiac arrest treated with hypothermia for 24 hours and grouped them
according to their neurological outcome to either "poor" or "favorable". Routine
laboratory indices were collected at constant time intervals up to one week of
admission. A comparison between the laboratory values in both groups was
performed. RESULTS: Between May 2008 to November 2011, 41 consecutive patients
with a mean age of 54.3 +/- 16.7 years were included in this study. No
significant correlation was found between routine laboratory indices and the
neurological outcome. The temporal trend of decay in the serum glucose values and
the ratio of polymorphonuclears to white blood cells during the first 72 hours
after admission was steeper in the favorable outcome group (P for trend < 0.05).
CONCLUSIONS: No single routine laboratory index was associated with neurological
outcome of survivors of cardiac arrest treated with hypothermia. The temporal
trends in both serum glucose and polymorphonuclear ratio signal a more intense
inflammatory response associated with poor outcome.
PMID- 28513118
TI - Metformin Does Not Induce Hyperlactatemia in Patients Admitted to Internal
Medicine Ward.
AB - BACKGROUND: Concerns about metformin-associated lactic acidosis (MALA) prohibit
the use of metformin in a large subset of diabetic patients, mostly in patients
with chronic kidney disease. Increasing evidence suggests that the current safety
regulations may be overly restrictive. OBJECTIVES: To examine the association
between chronic metformin treatment and lactate level in acute illness on the
first day of admission to an internal medicine ward. METHODS: We compared
diabetic and non-diabetic hospitalized patients treated or not treated with
metformin in different sets of kidney function. RESULTS: A total of 140 patients
participated in the study, 54 diabetic patients on chronic metformin treatment,
33 diabetic patients without metformin and 53 patients with no diabetes. Most
participants were admitted for conditions that prohibit metformin use, such as
heart failure, hypoxia and sepsis. Average lactate level was significantly higher
in the diabetes + metformin group compared to the diabetes non-metformin group.
Metformin treatment was not associated with higher than normal lactate level
(hyperlactatemia) or low pH. No patient was hospitalized for lactic acidosis as
the main diagnosis. CONCLUSIONS: Chronic metformin treatment mildly increases
lactate level, but does not induce hyperlactatemia or lactic acidosis in acute
illness on the first day of admission to an internal medicine ward. These data
support the expansion of metformin use.
PMID- 28513119
TI - Low Borderline Levels of Serum Vitamin B12 May Predict Cognitive Decline in
Elderly Hip Fracture Patients.
AB - BACKGROUND: The progression from cognitive impairment to dementia is a
multifactorial process that involves genetic and environmental factors. Vitamin
B12 deficiency can be an important factor in the progress from cognitive decline
to dementia. OBJECTIVES: To examine the relationship between borderline low level
of vitamin B12 (<= 350 pg/ml) and cognitive decline among a group of elderly hip
fracture patients. METHODS: This retrospective chart review study was conducted
in a geriatric rehabilitation ward of a university-affiliated referral hospital.
It comprised 91 elderly hip fracture patients. Cognition was assessed by the Mini
Mental State Examination (MMSE) tool. Fasting serum vitamin B12 levels were
measured within 24 hours after admission to the rehabilitation ward. RESULTS:
Twenty-two of the patients had vitamin B12 levels <= 350 pg/ml. In a multiple
linear regression analysis, after adjusting for confounding variables, serum
vitamin B12 levels <= 350 pg/ml were linked to a higher risk of developing
cognitive decline (beta coefficient = -0.28, P = 0.008). CONCLUSIONS: In our
study, serum vitamin B12 levels <= 350 pg/ml, were independently associated with
lower MMSE scores in elderly hip fracture patients. Serum vitamin B12 may assist
in identifying patients in the early stages of cognitive decline. This study
joins others that have reported on the association of low normal range vitamin
B12 blood levels and conditions like dementia, falls, fractures and frailty. We
suggest a reexamination of what is currently considered as the normal range of
vitamin B12 in the elderly.
PMID- 28513120
TI - Gestational Weight Gain and Its Relationship with Maternal Characteristics.
AB - BACKGROUND: Both high and insufficient weight gain during pregnancy have been
associated with adverse outcomes for mothers and their offspring. OBJECTIVES: To
describe self-reported weight gain during pregnancy, assess the concurrence of
this weight gain with issued recommendations, and investigate associations
between lifestyle factors and weight gain. METHODS: In this cross-sectional
study, 109 pregnant women hospitalized in one gynecological and obstetrics
department completed questionnaires related to weight gain and lifestyle factors
such as smoking, diet and exercise. Recommended weight gain was defined by the
American Congress of Obstetricians and Gynecologists and was compatible with the
Ministry of Health guidelines in Israel. RESULTS: Fifty-three (49%) participants
reported weight gain above the recommendation, 31 (28%) met the recommendations
and 25 (23%) reported weight gain below the recommendations. Characteristics
associated with high weight gain included past smoking and/or age above 36 years
and/or body mass index (BMI) above 25 kg/m2. Only 34 women (31%) reported seeking
professional nutritional counseling during pregnancy. An increased tendency to
consult a nutritionist was reported among diabetic women. CONCLUSIONS: Only a
minority of women gained the recommended weight during pregnancy. High BMI and/or
a history of smoking and/or older age were associated with weight gain above
recommendations. Particular effort should be directed toward counseling women at
high risk of weight gain during pregnancy.
PMID- 28513121
TI - Can Procalcitonin Contribute to the Diagnosis of Clostridium difficile Colitis?
AB - BACKGROUND: It is a challenge to diagnosis Clostridium difficile colitis.
OBJECTIVES: To determine, among patients who developed nosocomial diarrhea,
whether serum procalcitonin (PCT) can distinguish between C. difficile toxin
(CDT)-positive and CDT-negative patients. METHODS: This prospective study
included 50 adults (>18 years) who developed diarrhea during hospitalization, 25
with a positive fecal test for CDT (study group) and 25 CDT negative (control
group). RESULTS: Baseline demographic and underlying illnesses were similar in
both groups. Duration of diarrhea was 6 +/- 4 days and 3 +/- 1 in the study and
control groups, respectively (P = 0.001). Mean blood count was 20 +/- 15 and 9.9
+/- 4, respectively (P = 0.04). CRP level was higher in the study than in the
control group (10.9 +/- 7.4 and 6.6 +/- 4.8, P = 0.028). PCT level was higher in
the study group (4.4 +/- 4.9) than the control group (0.3 +/- 0.5, P = 0.102). A
PCT level > 2 ng/ml was found in 7/25 patients (28%) and 1/25 (4%), respectively
[odds ratio 9.33, 95% confidence interval (0.98 to 220), P = 0.049]. Multivariate
analysis showed that only duration of diarrhea and left shift of peripheral
leucocytes were significant indicators of CDT (P = 0.014 and P = 0.019,
respectively). The mortality rate was 12/25 (48%) vs. 5/25 (20%), respectively (P
= 0.04). CONCLUSIONS: We found a non-significant tendency to higher PCT levels in
patients with CDT-positive vs. CDT-negative nosocomial diarrhea. However, a PCT
level > 2 ng/ml may help distinguish between these patients.
PMID- 28513122
TI - The Many Faces of Non-Classic Congenital Adrenal Hyperplasia.
PMID- 28513123
TI - Urgent Endoscopic Stapler Zenker's Diverticulotomy in Acute Aphagia.
PMID- 28513124
TI - Definitive Endovascular Repair of a Brucellar Descending Thoracic Aortic
Aneurysm.
PMID- 28513125
TI - Pseudocirrhosis in Metastatic Breast Cancer.
PMID- 28513126
TI - Type 1 Gaucher disease with fatal outcome in a 17-year-old girl from Kazakhstan.
PMID- 28513129
TI - Electrodeposited Nickel-Cobalt-Sulfide Catalyst for the Hydrogen Evolution
Reaction.
AB - A novel Ni-Co-S-based material prepared by the potentiodynamic deposition from an
aqueous solution containing Ni2+, Co2+, and thiourea is studied as an
electrocatalyst for the hydrogen evolution reaction (HER) in a neutral phosphate
solution. The composition of the catalyst and the HER activity are tuned by
varying the ratio of the concentrations of Ni2+ and Co2+ ions in the
electrolytes. Under optimized deposition conditions, the bimetallic Ni-Co-S
exhibits higher electrocatalytic activity than its monometallic counterparts. The
Ni-Co-S catalyst requires an overpotential of 150 mV for the HER onset, and 10 mA
cm-2 current density is obtained at 280 mV overpotential. The catalyst exhibits
two different Tafel slopes (93 and 70 mV dec-1) indicating two dissimilar
mechanisms. It is proposed that the catalyst comprises two types of catalytic
active sites, and they contribute selectively toward HER in different potential
regions.
PMID- 28513127
TI - Shear-wave elastography in breast ultrasonography: the state of the art.
AB - Shear-wave elastography (SWE) is a recently developed ultrasound technique that
can visualize and measure tissue elasticity. In breast ultrasonography, SWE has
been shown to be useful for differentiating benign breast lesions from malignant
breast lesions, and it has been suggested that SWE enhances the diagnostic
performance of ultrasonography, potentially improving the specificity of
conventional ultrasonography using the Breast Imaging Reporting and Data System
criteria. More recently, not only has SWE been proven useful for the diagnosis of
breast cancer, but has also been shown to provide valuable information that can
be used as a preoperative predictor of the prognosis or response to chemotherapy.
PMID- 28513130
TI - Anisotropic Friction of Wrinkled Graphene Grown by Chemical Vapor Deposition.
AB - Wrinkle structures are commonly seen on graphene grown by the chemical vapor
deposition (CVD) method due to the different thermal expansion coefficient
between graphene and its substrate. Despite the intensive investigations focusing
on the electrical properties, the nanotribological properties of wrinkles and the
influence of wrinkle structures on the wrinkle-free graphene remain less
understood. Here, we report the observation of anisotropic nanoscale frictional
characteristics depending on the orientation of wrinkles in CVD-grown graphene.
Using friction force microscopy, we found that the coefficient of friction
perpendicular to the wrinkle direction was ~194% compare to that of the parallel
direction. Our systematic investigation shows that the ripples and "puckering"
mechanism, which dominates the friction of exfoliated graphene, plays even a more
significant role in the friction of wrinkled graphene grown by CVD. The
anisotropic friction of wrinkled graphene suggests a new way to tune the graphene
friction property by nano/microstructure engineering such as introducing
wrinkles.
PMID- 28513128
TI - Clinical features of recently diagnosed papillary thyroid carcinoma in elderly
patients aged 65 and older based on 10 years of sonographic experience at a
single institution in Korea.
AB - PURPOSE: The aim of this study was to assess the characteristics of papillary
thyroid carcinoma (PTC) in patients aged 65 and older in order to predict
postoperative recurrence based on the results of ultrasonographic surveillance.
METHODS: Among 1,494 patients (200 male and 1,294 female; mean age, 46.6+/-11.3
years) who underwent surgery for thyroid cancer at our institution between 2006
and 2015, we retrospectively enrolled 150 PTC patients (29 male and 121 female;
mean age, 69.4+/-4.2 years). To identify the risk factors for recurrence, we
analyzed age, gender, multiplicity, size, number, extrathyroidal extension (ETE)
of the tumor, lymph node metastasis (LNM), type of surgery, and the dose of
radioactive ablation using a Cox regression model to identify hazard ratios
(HRs). RESULTS: Among the 115 asymptomatic patients with PTCs detected by
screening ultrasonography (n=86), other cross-sectional imaging modalities
(computed tomography or positron emission tomography-computed tomography, n=13),
or incidentally through a surgical specimen (n=16), 78 patients were confirmed to
have papillary thyroid microcarcinomas (PTMCs). The other 35 patients presented
with palpable neck masses (n=25), vocal cord palsy (n=9) or blood-tinged sputum
(n=1). During the follow-up period (mean, 43.6 months), 17 patients (12.5%)
experienced recurrence in the neck. None of the patients died due to PTC-related
recurrence or distant metastasis during the follow-up period. Cox regression
analysis demonstrated that tumor size (HR, 2.12; P<0.001) and LNM (central LNM:
HR, 9.08; P=0.004; lateral LNM: HR, 14.71; P=0.002; both central and lateral LNM:
HR, 58.41; P<0.001) significantly increased the recurrence rate. ETE, LNM, and
recurrence were significantly less frequent in PTMCs than in non-PTMC (all
P<0.001). CONCLUSION: PTCs of small size and absent LNM showed significantly
better prognoses in patients 65 years and older.
PMID- 28513131
TI - Improved Oxidase Mimetic Activity by Praseodymium Incorporation into Ceria
Nanocubes.
AB - Ceria nanocubes (NC) modified with increasing concentrations of praseodymium (5,
10, 15, and 20 mol %) have been successfully synthesized by a hydrothermal
method. The as-synthesized Pr-modified ceria nanocubes exhibit an enhanced
oxidase-like activity on the organic dye TMB within a wide range of
concentrations and durations. The oxidase activity increases with increasing Pr
amounts in Pr-modified ceria nanocubes within the investigated concentration
range. Meanwhile, these Pr-modified ceria nanocubes also show higher reducibility
than pure ceria nanocubes. The kinetics of their oxidase mimetic activity is
fitted with the Michaelis-Menten equation. A mechanism has been proposed on how
the Pr incorporation could affect the energy level of the bands in ceria and
hence facilitate the TMB oxidation reaction. The presence of Pr3+ species on the
surface also contributes to the increasing activity of the Pr-modified ceria
nanocubes present higher oxidase activity than pure ceria nanocubes.
PMID- 28513132
TI - alpha-Amylase- and Redox-Responsive Nanoparticles for Tumor-Targeted Drug
Delivery.
AB - Paclitaxel (PTX) is an effective antineoplastic agent and shows potent antitumor
activity against a wide spectrum of cancers. Yet, the wide clinical use of PTX is
limited by its poor aqueous solubility and the side effects associated with its
current therapeutic formulation. To tackle these obstacles, we report, for the
first time, alpha-amylase- and redox-responsive nanoparticles based on
hydroxyethyl starch (HES) for the tumor-targeted delivery of PTX. PTX is
conjugated onto HES by a redox-sensitive disulfide bond to form HES-SS-PTX, which
was confirmed by results from NMR, high-performance liquid chromatography-mass
spectrometry, and Fourier transform infrared spectrometry. The HES-SS-PTX
conjugates assemble into stable and monodispersed nanoparticles (NPs), as
characterized with Dynamic light scattering, transmission electron microscopy,
and atomic force microscopy. In blood, alpha-amylase will degrade the HES shell
and thus decrease the size of the HES-SS-PTX NPs, facilitating NP extravasation
and penetration into the tumor. A pharmacokinetic study demonstrated that the HES
SS-PTX NPs have a longer half-life than that of the commercial PTX formulation
(Taxol). As a consequence, HES-SS-PTX NPs accumulate more in the tumor compared
with the extent of Taxol, as shown in an in vivo imaging study. Under reductive
conditions, the HES-SS-PTX NPs could disassemble quickly as evidenced by their
triggered collapse, burst drug release, and enhanced cytotoxicity against 4T1
tumor cells in the presence of a reducing agent. Collectively, the HES-SS-PTX NPs
show improved in vivo antitumor efficacy (63.6 vs 52.4%) and reduced toxicity in
4T1 tumor-bearing mice compared with those of Taxol. These results highlight the
advantages of HES-based alpha-amylase- and redox-responsive NPs, showing their
great clinical translation potential for cancer chemotherapy.
PMID- 28513133
TI - Antibacterial Property of a Polyethylene Glycol-Grafted Dental Material.
AB - Dental materials often cause bacterial adhesion and promote bacterial biofilm
formation, which brings a series of long-standing and significant problems in
oral health. However, the current development of antibacterial research in dental
devices is limited by the lack of materials endowed with good antibacterial
properties against oral bacteria. Here, we present a new strategy for reducing
the initial adhesion of bacterial on dental biomaterials by chemically bonding
long-chain polyethylene glycol. Our work represents an important step toward
solving the problem of bacterial accumulation on dental devices.
PMID- 28513134
TI - Silicon Quantum Dots in Dielectric Scattering Media: Broadband Enhancement of
Effective Absorption Cross Section by Light Trapping.
AB - We report strong enhancements of the effective absorption cross section and
photoluminescence (PL) intensity of silicon quantum dots (Si QDs) with 2.8-6.8 nm
in diameter in a highly scattering dielectric medium. The scattering medium is a
polymer thin film with submicrometer size pores inside, supporting the resonant
cavity modes in the visible range. By the scattering associated with the cavity
modes, efficient light trapping into a polymer film with ~1 MUm in thickness is
achieved, which leads to 30-40 times enhancement of the effective absorption
cross section of embedded Si QDs in a green-red wavelength range. The scattering
medium can also enhance up to 40 times the PL of QDs. Detailed analysis reveals
that the enhancements of the extraction efficiency as well as the excitation
efficiency contribute to the PL enhancement.
PMID- 28513135
TI - Porous MOF with Highly Efficient Selectivity and Chemical Conversion for CO2.
AB - A new Co(II)-based MOF, {[Co2(tzpa)(OH)(H2O)2].DMF}n (1) (H3tzpa = 5-(4-(tetrazol
5-yl)phenyl)isophthalic acid), was constructed by employing a tetrazolyl-carboxyl
ligand H3tzpa. 1 possesses 1D tubular channels that are decorated by MU3-OH
groups, uncoordinated carboxylate O atoms, and open metal centers generated by
the removal of coordinated water molecules, leading to high CO2 adsorption
capacity and significantly selective capture for CO2 over CH4 and CO in the
temperature range of 298-333 K. Moreover, 1 shows the chemical stability in
acidic and basic aqueous solutions. Grand canonical Monte Carlo simulations
identified multiple CO2-philic sites in 1. In addition, the activated 1 as the
heterogeneous Lewis and Bronsted acid bifunctional catalyst facilitates the
chemical fixation of CO2 coupling with epoxides into cyclic carbonates under
ambient conditions.
PMID- 28513137
TI - Hierarchical Porous Carbon Doped with Iron/Nitrogen/Sulfur for Efficient Oxygen
Reduction Reaction.
AB - Hierarchical porous Fe/N/S-doped carbon with a high content of graphitic nitrogen
(FeNS/HPC) has been successfully synthesized by a facile dual-template method.
FeNS/HPC shows not only macropores resulting from the dissolution of the SiO2
template, but abundant mesopores were also obtained after removing the in situ
generated Fe2O3 nanoparticles on the ultrathin (~4 nm) carbon shell of the
macropores. Moreover, micropores are produced during the thermal pyrolysis of the
carbon precursors. With respect to the electrochemical performance in the oxygen
reduction reaction (ORR), FeNS/HPC not only exceeds other prepared porous carbon
materials completely but also shows higher onset potential (0.97 vs 0.93 V), half
wave potentials (0.87 vs 0.83 V), and diffusion current density (5.5 vs 5.3 mA cm
2) than those of Pt/C. Furthermore, FeNS/HPC also exhibits outstanding stability
and methanol tolerance, making it a competent candidate for ORR. The following
aspects contribute to its excellent ORR performance. (1) High content of
graphitic N (5.1%) and codoping of pyridinic N species, thiophene-S, FeNx, and
graphitic carbon-encapsulated iron nanoparticles, providing highly active sites.
(2) The hierarchical porous mesh structure with micro-, meso-, and macroporosity,
accelerating the mass transfer and facilitating full utilization of the active
sites. (3) The high specific surface area (1148 m2 g-1) of the graphitic carbon
shell, assuring a large interface and rapid electron conduction for ORR.
PMID- 28513136
TI - Cold Chain-Free Storable Hydrogel for Infant-Friendly Oral Delivery of
Amoxicillin for the Treatment of Pneumococcal Pneumonia.
AB - Pneumonia is the major cause of death in children under five, particularly in
developing countries. Antibiotics such as amoxicillin greatly help in mitigating
this problem. However, there is a lack of an infant/toddler-friendly formulation
for countries with limited clean water orr electricity. Here, we report the
development of a shear-thinning hydrogel system for the oral delivery of
amoxicillin to infant/toddler patients, without the need of clean water and
refrigeration. The hydrogel formulation consists of metolose (hydroxypropyl
methylcellulose) and amoxicillin. It preserves the structural integrity of
antibiotics and their antibacterial activity over 12 weeks at room temperature.
Pharmacokinetic profiling of mice reveals that the hydrogel formulation increases
the bioavailability of drugs by ~18% compared to that with aqueous amoxicillin
formulation. More importantly, oral gavage of this formulation in a mouse model
of secondary pneumococcal pneumonia significantly ameliorates inflammatory
infiltration and tissue damage in lungs, with a 10-fold reduction in bacterial
counts compared to those in untreated ones. Given the remarkable antibacterial
efficacy as well as the use of FDA-regulated ingredients (metolose and
amoxicillin), the hydrogel formulation holds great promise for rapid clinical
translation.
PMID- 28513138
TI - In Situ Growth of Mesoporous Silica with Drugs on Titanium Surface and Its
Biomedical Applications.
AB - Mesoporous silica has been developed for the modification of titanium surfaces
that are used as implant materials. Yet, the traditional modification methods
failed to effectively construct mesoporous silica on the titanium surface evenly
and firmly, in which the interaction between mesoporous silica and titanium was
mainly physical. Here, in situ growth of mesoporous silica on a titanium surface
was performed using a simple evaporation-induced self-assembly strategy.
Meantime, in situ introduction of drugs (heparin and vancomycin) to mesoporous
silica was also adopted to improve the drug-loading amount. Both the above
mentioned processes were completed at the same time. Transmission electron
microscopy, N2 adsorption-desorption isotherms, Fourier transform infrared
spectroscopy, scanning electron microscopy, and water contact angle measurements
were used to characterize the structure of the mesoporous silica film. Results
indicated that the mesoporous silica film that in situ grew on the titanium
surface was smooth, thin, transparent, and stable. Cytotoxicity, proliferation
performance of osteoblast cells, and in vitro and in vivo studies of the
antibacterial activity of the coating were tested. This is the first study to
modify the titanium surface by the in situ growth of a mesoporous silica coating
with two kinds of drugs. The stability of the mesoporous silica coating can be
attributed to the chemical bonding between dopamine and silicon hydroxyl of the
mesoporous silica coating, and the smooth surface of mesoporous silica is a
result of the method of in situ growth. The large amount of drug-loading also
could be ascribed to the in situ introduction of drugs during the synthetic
process. The strategy proposed in this work will bring more possibilities for the
preparation of advanced functional materials based on the combination of
mesoporous structure and metallic materials.
PMID- 28513140
TI - Hybrid Prodrug Nanoparticles with Tumor Penetration and Programmed Drug
Activation for Enhanced Chemoresistant Cancer Therapy.
AB - Despite nanomedicine having shown great potential for reversing cancer cell
resistance, the suboptimal transport across multiple biological obstacles
seriously impedes its reaching targets at an efficacious level, which remains a
challenging hurdle for clinical success in resistant cancer therapy. Here, a
lipid-based hybrid nanoparticle was designed to efficiently deliver the
therapeutics to resistant cells and treat resistant cancer in vivo. The hybrid
nanoparticles (D-NPs/tetrandrine (TET)) are composed of a pH-responsive prodrug
1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE)-doxorubicin (DOX), an
efflux inhibitor TET, and a surfactant DSPE-[methoxy (poly(ethylene glycol))
2000] (DSPE-mPEG2000), which hierarchically combatted the sequential
physiological and pathological barriers of drug resistance and exhibited
prolonged blood circulation, high tumor accumulation, and deep tumor parenchyma
penetration. In the meantime, the programmed stepwise activation of encapsulated
TET and DOX suppressed the function of resistance-related P-glycoprotein in a
timely manner and facilitated the DOX sustained accommodation in tumor cells.
Through systematic studies, the results show that such a nanosystem dramatically
enhances drug potency and significantly overcomes the DOX resistance of breast
cancer with negligible systemic toxicities. These findings provide new strategies
to systemically combat chemoresistant cancers.
PMID- 28513139
TI - One-Step Facile Synthesis of Highly Magnetic and Surface Functionalized Iron
Oxide Nanorods for Biomarker-Targeted Applications.
AB - We report a one-step method for facile and sustainable synthesis of magnetic iron
oxide nanorods (or IONRs) with mean lengths ranging from 25 to 50 nm and mean
diameters ranging from 5 to 8 nm. The prepared IONRs are highly stable in aqueous
media and can be surface functionalized for biomarker-targeted applications. This
synthetic strategy involves the reaction of iron(III) acetylacetonate with
polyethyleneimine in the presence of oleylamine and phenyl ether, followed by
thermal decomposition. Importantly, the length and diameter as well as the aspect
ratio of the prepared IONRs can be controlled by modulating the reaction
parameters. We show that the resultant IONRs exhibit stronger magnetic properties
compared to those of the widely used spherical iron oxide nanoparticles (IONPs)
at the same iron content. The increased magnetic properties are dependent on the
aspect ratio, with the magnetic saturation gradually increasing from 10 to 75 emu
g-1 when increasing length of the IONRs, 5 nm in diameter, from 25 to 50 nm. The
magnetic resonance imaging (MRI) contrast-enhancing effect, as measured in terms
of the transverse relaxivity, r2, increased from 670.6 to 905.5 mM-1 s-1, when
increasing the length from 25 to 50 nm. When applied to the immunomagnetic cell
separation of the transferrin receptor (TfR)-overexpressed medulloblastoma cells
using transferrin (Tf) as the targeting ligand, Tf-conjugated IONRs can capture
92 +/- 3% of the targeted cells under a given condition (2.0 * 104 cells/mL, 0.2
mg Fe/mL concentration of magnetic materials, and 2.5 min of incubation time)
compared to only 37 +/- 2% when using the spherical IONPs, and 14 +/- 2% when
using commercially available magnetic beads, significantly improving the
efficiency of separating the targeted cells.
PMID- 28513141
TI - Application of Cu3InSnSe5 Heteronanostructures as Counter Electrodes for Dye
Sensitized Solar Cells.
AB - In this research, we reported the synthesis of quaternary Cu3InSnSe5
nanoparticles with uniform size distribution and morphology for the first time
through delicate controls over the chemical reaction kinetics. On the basis of
the preparation strategy of Cu3InSnSe5 nanoparticles, Pt-Cu3InSnSe5 and Au
Cu3InSnSe5 heteronanostructures were designed and yielded using a simple and
efficient seed growth method. These two heteronanostructures remained
monodispersed without presence of any Cu3InSnSe5 nanocrystal impurities. To
explore their application potentials for dye-sensitized solar cells, counter
electrodes consisting of individual Cu3InSnSe5, Pt-Cu3InSnSe5, or Au-Cu3InSnSe5
constituents were fabricated. Current density-voltage (J-V) characteristics
evaluation reveals that Cu3InSnSe5 nanoparticles, Pt-Cu3InSnSe5 and Au-Cu3InSnSe5
heterostructured nanoparticles display a comparative power conversion efficiency
(PCE) of 5.8%, 7.6%, and 6.5% to that of a Pt-based counter electrode (7.9%),
respectively. As such, we believe that the reported preparation strategy could
provide new insights to the design and manufacture of counter electrode materials
with controlled structure, morphology, and optimized power conversion efficiency
for dye-sensitized solar cells.
PMID- 28513142
TI - 12,13-Aziridinyl Epothilones. Stereoselective Synthesis of Trisubstituted
Olefinic Bonds from Methyl Ketones and Heteroaromatic Phosphonates and Design,
Synthesis, and Biological Evaluation of Potent Antitumor Agents.
AB - The synthesis and biological evaluation of a series of 12,13-aziridinyl
epothilone B analogues is described. These compounds were accessed by a
practical, general process that involved a 12,13-olefinic methyl ketone as a
starting material obtained by ozonolytic cleavage of epothilone B followed by
tungsten-induced deoxygenation of the epoxide moiety. The attachment of the
aziridine structural motif was achieved by application of the Ess-Kurti-Falck
aziridination, while the heterocyclic side chains were introduced via
stereoselective phosphonate-based olefinations. In order to ensure high (E)
selectivities for the latter reaction for electron-rich heterocycles, it became
necessary to develop and apply an unprecedented modification of the venerable
Horner-Wadsworth-Emmons reaction, employing 2-fluoroethoxyphosphonates that may
prove to be of general value in organic synthesis. These studies resulted in the
discovery of some of the most potent epothilones reported to date. Equipped with
functional groups to accommodate modern drug delivery technologies, some of these
compounds exhibited picomolar potencies that qualify them as payloads for
antibody drug conjugates (ADCs), while a number of them revealed impressive
activities against drug resistant human cancer cells, making them desirable for
potential medical applications.
PMID- 28513143
TI - Interactive Effects of Corrosion, Copper, and Chloramines on Legionella and
Mycobacteria in Hot Water Plumbing.
AB - Complexities associated with drinking water plumbing systems can result in
undesirable interactions among plumbing components that undermine engineering
controls for opportunistic pathogens (OPs). In this study, we examine the effects
of plumbing system materials and two commonly applied disinfectants, copper and
chloramines, on water chemistry and the growth of Legionella and mycobacteria
across a transect of bench- and pilot-scale hot water experiments carried out
with the same municipal water supply. We discovered that copper released from
corrosion of plumbing materials can initiate evolution of >1100 times more
hydrogen (H2) from water heater sacrificial anode rods than does presence of
copper dosed as soluble cupric ions. H2 is a favorable electron donor for
autotrophs and causes fixation of organic carbon that could serve as a nutrient
for OPs. Dosed cupric ions acted as a disinfectant in stratified stagnant pipes,
inhibiting culturable Legionella and biofilm formation, but promoted Legionella
growth in pipes subject to convective mixing. This difference was presumably due
to continuous delivery of nutrients to biofilm on the pipes under convective
mixing conditions. Chloramines eliminated culturable Legionella and prevented L.
pneumophila from recolonizing biofilms, but M. avium gene numbers increased by
0.14-0.76 logs in the bulk water and were unaffected in the biofilm. This study
provides practical confirmation of past discrepancies in the literature regarding
the variable effects of copper on Legionella growth, and confirms prior reports
of trade-offs between Legionella and mycobacteria if chloramines are applied as
secondary disinfectant residual.
PMID- 28513144
TI - Rapid Elemental Analysis of Aerosols Using Atmospheric Glow Discharge Optical
Emission Spectroscopy.
AB - A new, low-cost approach based on the application of atmospheric radio frequency
glow discharge (rf-GD) optical emission spectroscopy (OES) has been developed for
near real-time measurement of multielemental concentration in airborne
particulate phase. This method involves deposition of aerosol particles on the
tip of a cathode in a coaxial microelectrode system, followed by ablation,
atomization, and excitation of the particulate matter using the rf-GD. The
resulting atomic emissions are recorded using a spectrometer for elemental
identification and quantification. The glow discharge plasma in our system was
characterized by measuring spatially resolved gas temperatures (378-1438 K) and
electron densities (2-5 * 1014 cm-3). Spatial analysis of the spectral features
showed that the excitation of the analyte occurred in the region near the
collection electrode. The temporal analysis of spectral features in the rf-GD
showed that the collected particles were continuously ablated; the time for
complete ablation of 193 ng of sucrose particles was found to be approximately 2
s. The system was calibrated using 100 nm particles containing C, Cd, Mn, and Na,
respectively. The method provides limits of detection in the range of 0.055-1.0
ng, and a measurement reproducibility of 5-28%. This study demonstrates that the
rf-GD can be an excellent excitation source for the development of low-cost hand
held sensors for elemental measurement of aerosols.
PMID- 28513145
TI - Monodisperse Fiber-like Micelles of Controlled Length and Composition with an
Oligo(p-phenylenevinylene) Core via "Living" Crystallization-Driven Self
Assembly.
AB - We report the preparation of a series of fiber-like micelles of narrow length
distribution with an oligo(p-phenylenevinylene) (OPV)-core and a poly(N
isopropylacrylamide) (PNIPAM) corona via two different crystallization-driven
self-assembly (CDSA) strategies. The average length Ln of these micelles can be
varied up to 870 nm by varying the temperature in self-seeding experiments. In
addition, seeded growth was employed not only to prepare uniform micelles of
controlled length, but also to form fiber-like A-B-A triblock comicelles with an
OPV-core.
PMID- 28513146
TI - Insights into Antimony Adsorption on {001} TiO2: XAFS and DFT Study.
AB - Antimony (Sb) contamination poses an emerging environmental risk, whereas its
removal remains a contemporary challenge due to the lack of knowledge in its
surface chemistry and efficient adsorbent. In this study, self-assembly {001}
TiO2 was examined for its effectiveness in Sb removal, and the molecular level
surface chemistry was studied with X-ray absorption spectroscopy and density
functional theory calculations. The kinetics results show that Sb adsorption
followed the pseudo-second order reaction, and the Langmuir adsorption capacity
was 200 mg/g for Sb(III) and 156 mg/g for Sb(V). The PZC of TiO2, which was 6.6
prior to the adsorption experiment, shifted to 4.8 and <0 after adsorption of
Sb(III) and Sb(V), respectively, indicating the formation of negatively charged
inner-sphere complexes. EXAFS results suggest that Sb(III/V) adsorption exhibited
a bidentate binuclear surface complex. The orbital hybridizing of complexes was
studied by XANES, molecular orbital theory (MO), and density of states (DOS)
calculations. The change in orbital energy derived from orbital hybridizing of
adsorbed Sb on surfaces is the driving force underlining the Sb surface
chemistry. New bonds between Sb and TiO2 surface were formed with matched orbital
energies. Integrating the molecular and electronic structures into surface
complexation modeling reveals the nature of macroscopic Sb adsorption behaviors.
PMID- 28513147
TI - Four Specific Hapten Conformations Dominating Antibody Specificity: Quantitative
Structure-Activity Relationship Analysis for Quinolone Immunoassay.
AB - Antibody-based immunoassay methods have been important tools for monitoring drug
residues in animal foods. However, because of limited knowledge about the
quantitative structure-activity relationships between a hapten and its resultant
antibody specificity, antibody production with the desired specificity is still a
huge challenge. In this study, the three-dimensional quantitative structure
activity relationship (3D QSAR) was analyzed in accordance with the cross
reactivity of quinolone drugs reacting with the antibody raised by pipemidic acid
as the immunizing hapten and compared with the reported cross-reactivity data and
their hapten structures. It was found that the specificity of a quinolone
antibody was strongly related to the conformation of the hapten used and that
hapten conformations shaped like the letters "I", "P", and "Phi" were essential
for the desired high specificity with low cross-reactivity, but that the hapten
conformation shaped like the letter "Y" led to an antibody with broad specificity
and high cross-reactivity. Almost all of the antibodies against quinolones could
result from these four hapten conformations. It was first found that the concrete
conformations dominated the specificity of the antibody to quinolone, which will
be of significance for the accurate hapten design, predictable antibody
specificity, and better understanding the recognition mechanism between haptens
and the antibodies for immunoassays.
PMID- 28513148
TI - Correction to X-ray Absorption Spectroscopic Quantification and Speciation
Modeling of Sulfate Adsorption on Ferrihydrite Surfaces.
PMID- 28513149
TI - Vertical Profiles, Sources, and Transport of PFASs in the Arctic Ocean.
AB - The relative importance of atmospheric versus oceanic transport for poly- and
perfluorinated alkyl substances (PFASs) reaching the Arctic Ocean is not well
understood. Vertical profiles from the Central Arctic Ocean and shelf water, snow
and meltwater samples were collected in 2012; 13 PFASs (C6-C12 PFCAs; C6, 8, 10
PFSAs; MeFOSAA and EtFOSAA; and FOSA) were routinely detected (range: <5-343
pg/L). PFASs were only detectable above 150 m depth in the polar mixed layer
(PML) and halocline. Enhanced concentrations were observed in snow and meltpond
samples, implying atmospheric deposition as an important source of PFASs. Model
results suggested atmospheric inputs to account for 34-59% (~11-19 pg/L) of
measured PFOA concentrations in the PML (mean 32 +/- 15 pg/L). Modeled surface
and halocline measurements for PFOS based on North Atlantic inflow (11-36 pg/L)
agreed with measurements (mean, 17, range <5-41 pg/L). Modeled deep water
concentrations below 200 m (5-15 pg/L) were slightly higher than measurements (<5
pg/L), suggesting the lower bound of PFAS emissions estimates from wastewater and
rivers may provide the best estimate of inputs to the Arctic. Despite low
concentrations in deep water, this reservoir is expected to contain most of the
PFOS mass in the Arctic (63-180 Mg) and is projected to continue increasing to
2038.
PMID- 28513150
TI - Production of Caproic Acid from Mixed Organic Waste: An Environmental Life Cycle
Perspective.
AB - Caproic acid is an emerging platform chemical with diverse applications.
Recently, a novel biorefinery process, that is, chain elongation, was developed
to convert mixed organic waste and ethanol into renewable caproic acids. In the
coming years, this process may become commercialized, and continuing to improve
on the basis of numerous ongoing technological and microbiological studies. This
study aims to analyze the environmental performance of caproic acid production
from mixed organic waste via chain elongation at this current, early stage of
technological development. To this end, a life cycle assessment (LCA) was
performed to evaluate the environmental impact of producing 1 kg caproic acid
from organic waste via chain elongation, in both a lab-scale and a pilot-scale
system. Two mixed organic waste were used as substrates: the organic fraction of
municipal solid waste (OFMSW) and supermarket food waste (SFW). Ethanol use was
found to be the dominant cause of environmental impact over the life cycle.
Extraction solvent recovery was found to be a crucial uncertainty that may have a
substantial influence on the life-cycle impacts. We recommend that future
research and industrial producers focus on the reduction of ethanol use in chain
elongation and improve the recovery efficiency of the extraction solvent.
PMID- 28513151
TI - Acoustophoretic Mobility and Its Role in Optimizing Acoustofluidic Separations.
AB - In the separation sciences, sample species are separated according to their
physicochemical properties, the nature of the selective field, and, if present,
the properties of the medium in which they are dissolved or suspended.
Separations may be carried out on a continuous basis in microfluidic devices or
split-flow thin channel (SPLITT) devices by selectively transporting species in a
direction transverse to the direction of flow of the suspending fluid. Separation
is achieved in the so-called transport mode according to relative differences in
mobility of the species under the influence of the applied field. Gravitational,
centrifugal, thermal gradient, magnetic, electric, and dielectric fields may all
be used for continuous SPLITT fractionation. We present here the theory for
optimizing the operation of the relatively new technique of acoustic SPLITT
fractionation for the continuous separation of non-Brownian materials. The theory
is based on a quantitatively defined acoustophoretic mobility that is consistent
with the generalized concept of mobility proposed by Giddings. Until now,
acoustophoretic mobility has almost exclusively been used as a qualitative
descriptor for velocity induced by an acoustic field. The quantitative definition
presented here will contribute to the advancement of all forms of acoustofluidic
separations.
PMID- 28513154
TI - Role of Proton Tunneling and Metal-Free Organocatalysis in the Decomposition of
Methanediol: A Theoretical Study.
AB - Canonical variational transition state theory rate calculations have been
performed to assess the fate of methanediol in the troposphere. The calculations
suggest that proton tunneling plays a very important role in the gas-phase
decomposition of methanediol as it enhances the rate of the reaction by 1-9
orders of magnitude in the tropospherically relevant temperature range of 200-300
K. The effect of proton tunneling is greatest at 200 K; the rate constant is
enhanced up to 9 orders of magnitude. This is in stark contrast to previous
calculations suggesting that tunneling would not play any role in the alkanediol
decomposition under typical laboratory and interstellar conditions. Furthermore,
the results imply that though water is the most dominant trace component of the
troposphere, formic acid and the hydroperoxyl radical, which are relatively less
abundant, outcompete water in catalyzing the decomposition. Methanediol may also
catalyze its own decomposition below 280 K. However, this autocatalytic pathway
turns out to be less effective than the water-catalyzed one. These results may
play a crucial role in improving our understanding of alkanediol chemistry, which
has a broad appeal beyond the troposphere.
PMID- 28513153
TI - Sensitive Analysis of Protein Adsorption to Colloidal Gold by Differential
Centrifugal Sedimentation.
AB - It is demonstrated that the adsorption of bovine serum albumin (BSA) to aqueous
gold colloids can be quantified with molecular resolution by differential
centrifugal sedimentation (DCS). This method separates colloidal particles of
comparable density by mass. When proteins adsorb to the nanoparticles, both their
mass and their effective density change, which strongly affects the sedimentation
time. A straightforward analysis allows quantification of the adsorbed layer.
Most importantly, unlike many other methods, DCS can be used to detect
chemisorbed proteins ("hard corona") as well as physisorbed proteins ("soft
corona"). The results for BSA on gold colloid nanoparticles can be modeled in
terms of Langmuir-type adsorption isotherms (Hill model). The effects of surface
modification with small thiol-PEG ligands on protein adsorption are also
demonstrated.
PMID- 28513152
TI - A Molecular Mechanism for Nonphotochemical Quenching in Cyanobacteria.
AB - The cyanobacterial orange carotenoid protein (OCP) protects photosynthetic
cyanobacteria from photodamage by dissipating excess excitation energy collected
by phycobilisomes (PBS) as heat. Dissociation of the PBS-OCP complex in vivo is
facilitated by another protein known as the fluorescence recovery protein (FRP),
which primarily exists as a dimeric complex. We used various mass spectrometry
(MS)-based techniques to investigate the molecular mechanism of this FRP-mediated
process. FRP in the dimeric state (dFRP) retains its high affinity for the C
terminal domain (CTD) of OCP in the red state (OCPr). Site-directed mutagenesis
and native MS suggest the head region on FRP is a candidate to bind OCP. After
attachment to the CTD, the conformational changes of dFRP allow it to bridge the
two domains, facilitating the reversion of OCPr into the orange state (OCPo)
accompanied by a structural rearrangement of dFRP. Interestingly, we found a
mutual response between FRP and OCP; that is, FRP and OCPr destabilize each
other, whereas FRP and OCPo stabilize each other. A detailed mechanism of FRP
function is proposed on the basis of the experimental results.
PMID- 28513155
TI - Degradation Kinetics of 6'''-p-Coumaroylspinosin and Identification of Its
Metabolites by Rat Intestinal Flora.
AB - 6'''-p-Coumaroylspinosin (P-CS), a bioactive flavonoid, is typically extracted
from Semen Ziziphi Spinosae (SZS). In this study, a high-performance liquid
chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed to
determine P-CS for investigating the degradation characteristics of P-CS
incubated with rat feces. The results showed that P-CS degraded rapidly and the
degradation speeds varied depending upon the P-CS concentrations (3, 15, and 30
MUg/mL). The degradation of P-CS processes follow first-order kinetics. On the
basis of the mass spectrometry (MS) spectrum mode of the product ions, two main
metabolites of P-CS were identified. Swertisin was the main metabolite at 3 and
15 MUg/mL, while spinosin was produced when the P-CS concentration was 30 MUg/mL.
Spinosin and swertisin could improve mRNA transcription levels of glutamate
receptor K1, K2, and K3 (GluK1, GluK2, and GluK3) subunits in rat hippocampal
neurons. In addition, they showed an obvious synergistic effect in this respect.
Collectively, the results can be used to explain the metabolic and
pharmacological mechanisms of P-CS.
PMID- 28513156
TI - Quantum Chemical Investigation on Photochemical Reactions of Nonanoic Acids at
Air-Water Interface.
AB - Photoinduced chemical reactions of organic compounds at the marine boundary layer
have recently attracted significant experimental attention because this kind of
photoreactions has been proposed to have substantial impact on local new particle
formation and their photoproducts could be a source of secondary organic
aerosols. In this work, we have employed first-principles density functional
theory method combined with cluster models to systematically explore
photochemical reaction pathways of nonanoic acids (NAs) to form volatile
saturated and unsaturated C9 and C8 aldehydes at air-water interfaces. On the
basis of the results, we have found that the formation of C9 aldehydes is not
initiated by intermolecular Norrish type II reaction between two NAs but by
intramolecular T1 C-O bond fission of NA generating acyl and hydroxyl radicals.
Subsequently, saturated C9 aldehydes are formed through hydrogenation reaction of
acyl radical by another intact NA. Following two dehydrogenation reactions,
unsaturated C9 aldehydes are generated. In parallel, the pathway to C8 aldehydes
is initiated by T1 C-C bond fission of NA, which generates octyl and carboxyl
radicals; then, an octanol is formed through recombination reaction of octyl with
hydroxyl radical. In the following, two dehydrogenation reactions result into an
enol intermediate from which saturated C8 aldehydes are produced via NA-assisted
intermolecular hydrogen transfer. Finally, two dehydrogenation reactions generate
unsaturated C8 aldehydes. In these reactions, water and NA molecules are found to
play important roles. They significantly reduce relevant reaction barriers. Our
work has also explored oxygenation reactions of NA with molecular oxygen and
radical-radical dimerization reactions.
PMID- 28513157
TI - Shedding Light on the Accuracy of Optimally Tuned Range-Separated Approximations
for Evaluating Oxidation Potentials.
AB - There is a surge in the literature on the development of exchange-correlation
density functionals for a wide variety of physical and chemical properties. As a
recent endeavor toward the systematic and nonempirical design of density
functional approximations, optimally tuned range-separated hybrid (OT-RSH) models
have been introduced. In this work, we propose novel OT-RSH density functionals
for predicting the oxidation potentials of organic compounds from different
categories. In this regard, detailed analysis of the role of nonempirical
optimization of the range separation parameter and importance of short- and long
range exact-like exchange in OT-RSH calculations of the oxidation potential has
also been done. It is shown that the newly developed OT-RSH approximations not
only perform better than other standard long-range corrected functionals but also
in many cases outperform other conventional hybrid functionals with a fixed
amount of exact-like exchange. Plus, we find that the proposed functionals
describe well the oxidation potentials of compounds for which the tuning of the
range separation parameter was not performed. From a different perspective,
accountability of the computed frontier orbital energies from the OT-RSH density
functionals for estimation of oxidation potentials has also been evaluated. Our
results reveal that the negative highest occupied molecular orbital energies of
molecules and the negative lowest unoccupied molecular orbital energies of their
cations correlate remarkably with the observed oxidation potentials. Admittedly,
with more efforts along this line, modern OT-RSH functionals with broader
applicability can be released for computational electrochemistry.
PMID- 28513158
TI - Molecular Optimization Enables over 13% Efficiency in Organic Solar Cells.
AB - A new polymer donor (PBDB-T-SF) and a new small molecule acceptor (IT-4F) for
fullerene-free organic solar cells (OSCs) were designed and synthesized. The
influences of fluorination on the absorption spectra, molecular energy levels,
and charge mobilities of the donor and acceptor were systematically studied. The
PBDB-T-SF:IT-4F-based OSC device showed a record high efficiency of 13.1%, and an
efficiency of over 12% can be obtained with a thickness of 100-200 nm, suggesting
the promise of fullerene-free OSCs in practical applications.
PMID- 28513159
TI - Accurate Anharmonic Zero-Point Energies for Some Combustion-Related Species from
Diffusion Monte Carlo.
AB - Full-dimensional analytic potential energy surfaces based on CCSD(T)/cc-pVTZ
calculations have been determined for 48 small combustion-related molecules. The
analytic surfaces have been used in Diffusion Monte Carlo calculations of the
anharmonic zero-point energies. The resulting anharmonicity corrections are
compared to vibrational perturbation theory results based both on the same level
of electronic structure theory and on lower-level electronic structure methods
(B3LYP and MP2).
PMID- 28513160
TI - Formation of Free and Protein-Bound Heterocyclic Amines in Roast Beef Patties
Assessed by UPLC-MS/MS.
AB - The effect of different roasting temperatures on the amounts of 17 heterocyclic
amines (HAs) from seven categories of both free and protein-bound states in roast
beef patties was assessed using an ultraperformance liquid chromatography-tandem
mass spectrometry (UPLC-MS/MS) method. There were increased amounts and more
types of HAs detected at higher roasting temperatures. Nine free HAs were
detected at 250 degrees C, including PhIP (14.34 +/- 0.36 ng/g), DMIP (1.02 +/-
0.07 ng/g), 1,5,6-TMIP (1.70 +/- 0.08 ng/g), MeIQ (0.36 +/- 0.01 ng/g), IQx (0.37
+/- 0.04 ng/g), MeIQx (9.94 +/- 0.61 ng/g), 4,8-DiMeIQx (0.90 +/- 0.05 ng/g),
norharman (6.03 +/- 0.30 ng/g), and harman (2.60 +/- 0.09 ng/g). Also, 37.32 ng/g
of total free HAs was generated. Twelve protein-bound HAs were detected in roast
beef patties at 250 degrees C, including PhIP (1.70 +/- 0.13 ng/g), DMIP (2.33
+/- 0.25 ng/g), 1,5,6-TMIP (3.62 +/- 0.49 ng/g), MeIQ (5.47 +/- 0.18 ng/g),
IQ[4,5-b] (0.70 +/- 0.03 ng/g) MeIQx (4.03 +/- 0.41 ng/g), 4,8-DiMeIQx (0.67 +/-
0.09 ng/g), MeAalphaC (19.51 +/- 1.12 ng/g), AalphaC (2.91 +/- 0.45 ng/g),
norharman (1304.96 +/- 110.73 ng/g), harman (400.85 +/- 25.29 ng/g), and Phe-P-1
(0.81 +/- 0.06 ng/g). The highest amount of protein-bound HAs was 2913.31 ng/g at
175 degrees C. PhIP tended to exist in a free state, whereas MeIQ, harman, and
norharman tended to exist in a protein-bound state. Furthermore, Phe-P-1,
MeAalphaC, and AalphaC were detected only in a protein-bound state. These results
could be useful for evaluating the exposure to HAs in a daily diet.
PMID- 28513162
TI - Radical C-H Fluorination Using Unprotected Amino Acids as Radical Precursors.
AB - We report a unique example of utilizing unprotected amino acids for benzylic C-H
fluorination via a radical process. alpha-Aminoalkyl radicals are readily
generated via oxidative decarboxylation of unprotected amino acids using a simple
silver(I) catalyst and Selectfluor, which serves as both a mild oxidant and
source of electrophilic fluorine. Mechanistic investigation shows that
coordination of the unprotected amino acid plays a crucial role in lowering the
oxidation potential of Ag(I), enabling oxidation under mild conditions. Mono- or
difluorination is possible by controlling the stoichiometry of amino acid and
fluorine source.
PMID- 28513161
TI - Improved Synthesis for Modular Ascarosides Uncovers Biological Activity.
AB - A versatile synthesis of modular ascarosides, a family of signaling molecules
from Caenorhabditis elegans and other nematodes, via hydrogenolysis of a cyclic
sulfate derived from methyl-alpha-l-rhamnopyranoside is reported. The route
enables selective introduction of different side chains at the 1, 2, and 4
positions of the sugar, as demonstrated for ascarosides from C. elegans and
Pristionchus pacificus. Bioassays with synthetic samples of 4'-tigloyl ascaroside
mbas#3 revealed its role as an avoidance or dispersal signal.
PMID- 28513163
TI - Bronsted Base Mediated Stereoselective Diphosphination of Terminal Alkynes with
Diphosphanes.
AB - A Bronsted base mediated stereoselective diphosphination of terminal alkynes with
diphosphanes proceeds to deliver the corresponding (E)-1,2-diphosphinoethenes in
good yields. The reaction of aromatic alkynes occurs efficiently in the presence
of a catalytic amount of LiO-t-Bu while MN(TMS)2 (M = Li or Na) gave better
results in the case of aliphatic substrates. The Bronsted base mediated protocol
can offer a good alternative to precedented transition-metal-catalyzed or radical
promoted approaches to the 1,2-diphosphinoethene framework of potent interest in
catalysis and coordination chemistry.
PMID- 28513164
TI - Total Synthesis of Neomarchantin A: Key Bond Constructions Performed Using
Continuous Flow Methods.
AB - A synthesis of neomarchantin A has been achieved wherein key bond constructions
involving C-O or C-C bond formations were augmented via continuous flow
techniques. Of note, the synthesis of neomarchantin A represents the first
demonstration of catalytic macrocyclic olefin metathesis as a key step for the
synthesis of a macrocyclic bisbibenzyl natural product.
PMID- 28513165
TI - alpha-CASSCF: An Efficient, Empirical Correction for SA-CASSCF To Closely
Approximate MS-CASPT2 Potential Energy Surfaces.
AB - Because of its computational efficiency, the state-averaged complete active-space
self-consistent field (SA-CASSCF) method is commonly employed in nonadiabatic ab
initio molecular dynamics. However, SA-CASSCF does not effectively recover
dynamical correlation. As a result, there can be qualitative differences between
SA-CASSCF potential energy surfaces (PESs) and more accurate reference surfaces
computed using multistate complete active space second-order perturbation theory
(MS-CASPT2). Here we introduce an empirical correction to SA-CASSCF that scales
the splitting between individual states and the state-averaged energy. We call
this the alpha-CASSCF method, and we show here that it significantly improves the
accuracy of relative energies and PESs compared with MS-CASPT2 for the
chromophores of green fluorescent and photoactive yellow proteins. As such, this
method may prove to be quite valuable for nonadiabatic dynamics.
PMID- 28513166
TI - Bronsted Acid Catalyzed Nitrile Synthesis from Aldehydes Using Oximes via
Transoximation at Ambient Temperature.
AB - The Bronsted acid-catalyzed synthesis of nitriles is described via transoximation
under mild conditions using an O-protected oxime as a more stable equivalent of
explosive O-protected hydroxylamines. The nitrile was generated via an O
protected aldoxime produced from the aldehyde and an O-protected oxime through
transoximation. The reaction could be performed on a 1 g scale.
PMID- 28513168
TI - Influence of Rotator Design on the Speed of Self-Assembled Four-Component
Nanorotors: Coordinative Versus Dispersive Interactions.
AB - Four-component nanorotors are prepared by the self-assembly of stator [Cu4(4)]4+
with its four copper(I)-loaded phenanthroline stations and various rotators
carrying one, two, or three pyridine terminals. The fourth component, 1,4
diazabicyclo[2.2.2]octane, serves as a connecting axle between rotator and
stator. Capitalizing on the heteroleptic pyridyl and phenanthroline metal
complexes concept, the rotator's pyridine terminals are connected to the
copper(I)-loaded phenanthroline stations (Npy -> [Cu(phen)]+) in the STOP state
and disconnected in the transition state of rotation. As the barrier of the
thermally activated rotation, measured by variable-temperature 1H NMR, is mainly
governed by attractive forces between stator stations and rotator terminals, it
increases along the series Ea (monopyridine rotator) < Ea (dipyridine rotator) <
Ea (tripyridine rotator). However, there are even distinct differences in rate
between rotors with equal number of rotator terminals. The change from the 5,10
dipyridyl (cis) to 5,15-dipyridyl (trans) zinc porphyrin rotator enhances the
rotational frequency by almost 1000-fold. Density functional theory computational
results suggest that not only coordinative Npy -> [Cu(phen)]+ interactions but
also dispersive attraction influence the barrier of rotation.
PMID- 28513169
TI - Structural and Magnetic Properties of the Osmium Double Perovskites Ba2
xSrxYOsO6.
AB - The crystal and magnetic structures of double perovskites of the type Ba2
xSrxYOsO6 were studied by synchrotron X-ray and neutron powder diffraction
methods, bulk magnetic susceptibility measurements, and X-ray absorption
spectroscopy. The structures were refined using combined neutron and synchrotron
data sets based on an ordered array of corner-sharing YO6 and OsO6 octahedra,
with the Ba/Sr cations being completely disordered. The structure evolves from
cubic to monoclinic Fm3m (x ~ 0.6) -> I4/m (x ~ 1.0) -> I2/m (x ~ 1.6) -> P21/n
as the Sr content is increased, due to the introduction of cooperative tilting of
the octahedra. Bulk magnetic susceptibility measurements demonstrate the oxides
are all anti-ferromagnets. The decrease in symmetry results in a nonlinear
increase in the Neel temperature. Low-temperature neutron diffraction
measurements of selected examples show these to be type-I anti-ferromagnets. X
ray absorption spectra collected at the Os L3- and L2-edges confirm the Os is
pentavalent in all cases, and there is no detectable change in the covalency of
the Os cation as the A-cation changes. Analysis of the L3/L2 branching ratio
shows that the spin-orbit coupling is constant and insignificant across the
series.
PMID- 28513167
TI - Quercetin, Morin, Luteolin, and Phloretin Are Dietary Flavonoid Inhibitors of
Monocarboxylate Transporter 6.
AB - Monocarboxylate transporter 6 (MCT6; SLC16A5) has been recognized for its role as
a xenobiotic transporter, with characterized substrates probenecid, bumetanide,
and nateglinide. To date, the impact of commonly ingested dietary compounds on
MCT6 function has not been investigated, and therefore, the objective of this
study was to evaluate a variety of flavonoids for their potential MCT6-specific
interactions. Flavonoids are a large group of polyphenolic phytochemicals found
in commonly consumed plant-based products that have been recognized for their
dietary health benefits. The uptake of bumetanide in human MCT6 gene-transfected
Xenopus laevis oocytes was significantly decreased in the presence of a variety
of flavonoids (e.g., quercetin, luteolin, phloretin, and morin), but was not
significantly affected by flavonoid glycosides (e.g., naringin, rutin,
phlorizin). The IC50 values of quercetin, phloretin, and morin were determined to
be 25.3 +/- 3.36, 17.3 +/- 2.37, and 33.1 +/- 3.29 MUM, respectively. The
mechanism of inhibition of phloretin was reversible and competitive, with a Ki
value of 22.8 MUM. Furthermore, typical MCT substrates were also investigated for
their potential interactions with MCT6. Substrates of MCTs 1, 2, 4, 8, and 10 did
not cause any significant decrease in MCT6-mediated bumetanide uptake, suggesting
that MCT6 has distinct compound selectivity. In summary, these results suggest
that dietary aglycon flavonoids may significantly alter the pharmacokinetics and
pharmacodynamics of bumetanide and other MCT6-specific substrates, and may
represent potential substrates for MCT6.
PMID- 28513170
TI - Phospholipid-Biomimetic Fluorescent Mitochondrial Probe with Ultrahigh
Selectivity Enables In Situ and High-Fidelity Tissue Imaging.
AB - In situ and directly imaging mitochondria in tissues instead of isolated cells
can offer more native and accurate information. Particularly, in the clinical
diagnose of mitochondrial diseases such as mitochondrial myopathy, it is a
routine examination item to directly observe mitochondrial morphology and number
in muscle tissues from patients. However, it is still a challenging task because
the selectivity of available probes is inadequate for exclusively tissue imaging.
Inspired by the chemical structure of amphiphilic phospholipids in mitochondrial
inner membrane, we synthesized a phospholipid-biomimetic amphiphilic fluorescent
probe (Mito-MOI) by modifying a C18-alkyl chain to the lipophilic side of
carbazole-indolenine cation. Thus, the phospholipid-like Mito-MOI locates at
mitochondrial inner membrane through electrostatic interaction between its cation
and inner membrane negative charge. Simultaneously, the C18-alkyl chain, as the
second targeting group, is deeply embedded into the hydrophobic region of inner
membrane through hydrophobic interaction. Therefore, the dual targeting groups
(cation and C18-alkyl chain) actually endow Mito-MOI with ultrahigh selectivity.
As expected, high-resolution microscopic photos showed that Mito-MOI indeed
stained mitochondrial inner membrane. Moreover, in situ and high-fidelity tissue
imaging has been achieved, and particularly, four kinds of mitochondria and their
crystal-like structure in muscle tissues were visualized clearly. Finally, the
dynamic process of mitochondrial fission in living cells has been shown. The
strategy employing dual targeting groups should have reference value for
designing fluorescent probes with ultrahigh selectivity to various intracellular
membranous components.
PMID- 28513171
TI - Ni(II) Complexes of the Redox-Active Bis(2-aminophenyl)dipyrrin: Structural,
Spectroscopic, and Theoretical Characterization of Three Members of an Electron
Transfer Series.
AB - The sterically hindered bis(2-aminophenyl)dipyrrin ligand H3NL was prepared. X
ray diffraction discloses a bifurcated hydrogen bonding network involving the
dipyrrin and one aniline ring. The reaction of H3NL with one equivalent of
nickel(II) in the air produces a paramagnetic neutral complex, which absorbs
intensively in the Vis-NIR region. Its electron paramagnetic resonance spectrum
displays resonances at g1 = 2.033, g2 = 2.008, and g3 = 1.962 that are
reminiscent of an (S = 1/2) system having a predominant organic radical
character. Both the structural investigation (X-ray diffraction) and density
functional theory calculations on [NiII(NL*)] points to an unprecedented mixed
"pyrrolyl-anilinyl" radical character. The neutral complex [NiII(NL*)] exhibits
both a reversible oxidation wave at -0.28 V vs Fc+/Fc and a reversible reduction
wave at -0.91 V. The anion was found to be highly air-sensitive, but could be
prepared by reduction with cobaltocene and structurally characterized. It
comprises a Ni(II) ion coordinated to a closed-shell trianionic ligand and hence
can be formulated as [NiII(NL)]-. The cation was generated by reacting
[NiII(NL*)] with one equivalent of silver hexafluoroantimonate. By X-ray
diffraction we established that it contains an oxidized, closed-shell ligand
coordinated to a nickel(II) ion. We found that a reliable hallmark for both the
oxidation state of the ligand and the extent of delocalization within the series
is the bond connecting the dipyrrin and the aniline, which ranges between 1.391 A
(cation) and 1.449 A (anion). The cation and anion exhibit a rich Vis-NIR
spectrum, despite their nonradical nature. The low energy bands correspond to
ligand-based electronic excitations. Hence, the HOMO-LUMO gap is small, and the
redox processes in the electron transfer series are exclusively ligand-centered.
PMID- 28513172
TI - A Quantum Chemical Interpretation of Two-Dimensional Electronic Spectroscopy of
Light-Harvesting Complexes.
AB - Nonlinear electronic spectroscopies represent one of the most powerful techniques
to study complex multichromophoric architectures. For these systems, in fact,
linear spectra are too congested to be used to disentangle the many coupled
vibroelectronic processes that are activated. By using a 2D approach, instead, a
clear picture can be achieved, but only when the recorded spectra are combined
with a proper interpretative model. So far, this has been almost always achieved
through parametrized exciton Hamiltonians that necessarily introduce biases
and/or arbitrary assumptions. In this study, a first-principles approach is
presented that combines accurate quantum chemical descriptions with state-of-the
art models for the environment through the use of atomistic and polarizable
embeddings. Slow and fast bath dynamics, along with exciton transport between the
pigments, are included. This approach is applied to the 2DES spectroscopy of the
Light-Harvesting 2 (LH2) complex of purple bacteria. Simulations are extended
over the entire visible-near-infrared spectral region to cover both carotenoid
and bacteriochlorophyll signals. Our results provide an accurate description of
excitonic properties and relaxation pathways, and give an unprecedented insight
into the interpretation of the spectral signatures of the measured 2D signals.
PMID- 28513173
TI - Photophysics of Deoxycytidine and 5-Methyldeoxycytidine in Solution: A
Comprehensive Picture by Quantum Mechanical Calculations and Femtosecond
Fluorescence Spectroscopy.
AB - The study concerns the relaxation of electronic excited states of the DNA
nucleoside deoxycytidine (dCyd) and its methylated analogue 5-methyldeoxycytidine
(5mdCyd), known to be involved in the formation of UV-induced lesions of the
genetic code. Due to the existence of four closely lying and potentially coupled
excited states, the deactivation pathways in these systems are particularly
complex and have not been assessed so far. Here, we provide a complete
mechanistic picture of the excited state relaxation of dCyd/5mdCyd in three
solvents-water, acetonitrile, and tetrahydrofuran-by combining femtosecond
fluorescence experiments, addressing the effect of solvent proticity on the
relaxation dynamics of dCyd and 5mdCyd for the first time, and two complementary
quantum mechanical approaches (CASPT2/MM and PCM/TD-CAM-B3LYP). The lowest energy
pipi* state is responsible for the sub-picosecond lifetime observed for dCyd in
all the solvents. In addition, computed excited state absorption and transient IR
spectra allow one, for the first time, to assign the tens of picoseconds time
constant, reported previously, to a dark state (nOpi*) involving the carbonyl
lone pair. A second low-lying dark state, involving the nitrogen lone pair
(nNpi*), does significantly participate in the excited state dynamics. The 267 nm
excitation of dCyd leads to a non-negligible population of the second bright
pipi* state, which affects the dynamics, acting mainly as a "doorway" state for
the nOpi* state. The solvent plays a key role governing the interplay between the
different excited states; unexpectedly, water favors population of the dark
states. In the case of 5mdCyd, an energy barrier present on the main nonradiative
decay route explains the 6-fold lengthening of the excited state lifetime
compared to that of dCyd, observed for all the examined solvents. Moreover, C5
methylation destabilizes both nOpi* and nNpi* dark states, thus preventing them
from being populated.
PMID- 28513174
TI - Structure-Activity Relationship of Curcumin: Role of the Methoxy Group in Anti
inflammatory and Anticolitis Effects of Curcumin.
AB - Curcumin, a dietary compound from turmeric, has beneficial effects on
inflammatory diseases such as inflammatory bowel disease. Most previous studies
have focused on the structure-activity relationship of the thiol-reactive
alpha,beta-unsaturated carbonyl groups of curcumin, so little is known about the
roles of methoxy groups in biological activities of curcumin. Here we synthesized
a series of curcumin analogues with different substitution groups (R = H-, Br-,
Cl-, F-, NO2-, CH3-, and OH-) to replace the methoxy group and evaluated their
biological effects in vitro and in vivo. Curcumin, Cur-OH, and Cur-Br (25 MUM)
suppressed 74.91 +/- 0.88, 77.75 +/- 0.89, and 71.75 +/- 0.90% of LPS-induced NO
production, respectively (P < 0.05). Similarly, these compounds also decreased
iNOS expression, COX-2 expression, and NF-kappaB signaling in RAW 264.7
macrophage cells (P < 0.05). However, other analogues, especially Cur-NO2, were
inactive (P > 0.05). In the dextran sulfate sodium (DSS)-induced colitis mouse
model, the Cur-Br analogue also showed a beneficial effect the same as curcumin
(P < 0.05), whereas the Cur-NO2 analogue had no effect in the animal model (P >
0.05). Together, the analogues have dramatically different effects on
inflammation, supporting that the substitution group on the methoxy position
plays an important role in the anti-inflammatory effects of curcumin. The methoxy
group is a potential structural candidate for modification to design curcumin
based drugs for inflammatory diseases.
PMID- 28513175
TI - Effect of VOC Emissions from Vegetation on Air Quality in Berlin during a
Heatwave.
AB - The potential of emissions from urban vegetation combined with anthropogenic
emissions to produce ozone and particulate matter has long been recognized. This
potential increases with rising temperatures and may lead to severe problems with
air quality in densely populated areas during heat waves. Here, we investigate
how heat waves affect emissions of volatile organic compounds from urban/suburban
vegetation and corresponding ground-level ozone and particulate matter. We use
the Weather Research and Forecasting Model with atmospheric chemistry (WRF-Chem)
with emissions of volatile organic compounds (VOCs) from vegetation simulated
with MEGAN to quantify some of these feedbacks in Berlin, Germany, during the
heat wave in 2006. The highest ozone concentration observed during that period
was ~200 MUg/m3 (~101 ppbV). The model simulations indicate that the contribution
of biogenic VOC emissions to ozone formation is lower in June (9-11%) and August
(6-9%) than in July (17-20%). On particular days within the analyzed heat wave
period, this contribution increases up to 60%. The actual contribution is
expected to be even higher as the model underestimates isoprene concentrations
over urban forests and parks by 0.6-1.4 ppbv. Our study demonstrates that
biogenic VOCs can considerably enhance air pollution during heat waves. We
emphasize the dual role of vegetation for air quality and human health in cities
during warm seasons, which is removal and lessening versus enhancement of air
pollution. The results of our study suggest that reduction of anthropogenic
sources of NOx, VOCs, and PM, for example, reduction of the motorized vehicle
fleet, would have to accompany urban tree planting campaigns to make them really
beneficial for urban dwellers.
PMID- 28513177
TI - Hydrogen Bonded Structures of Confined Water Molecules and Electric Field Induced
Shift of Their Equilibrium Revealed by IR Electroabsorption Spectroscopy.
AB - Water confined on a nanometer scale plays an essential role in various chemical
and biological processes. Confined water molecules are often exposed to electric
fields as manifested by those that occur on protein surfaces or in electrical
double layers, but the electric field effects on confined water are not fully
understood. We used IR electroabsorption (EA) spectroscopy with unprecedented
sensitivity to observe electric-field-induced changes in the OH stretching
absorption of water (H2O) molecules dissolved in 1,4-dioxane, which constitute a
simple model system for confined water. A multivariate curve resolution analysis
of the normal IR spectra (without an electric field) of water in 1,4-dioxane at
different concentrations indicates the presence of the monomer and dimer of the
confined water molecules and equilibrium between them. We find that the IR EA
spectrum that is free from the contribution of field-induced molecular
reorientation is mainly attributable to a field-induced shift of the equilibrium
toward the dimer. This result demonstrates a possible control of the polarity of
confined water by simply applying an external electric field and the ability of
our method to elucidate how it is achieved.
PMID- 28513176
TI - Selective Inhibition of Escherichia coli RNA and DNA Topoisomerase I by Hoechst
33258 Derived Mono- and Bisbenzimidazoles.
AB - A series of Hoechst 33258 based mono- and bisbenzimidazoles have been synthesized
and their Escherichia coli DNA topoisomerase I inhibition, binding to B-DNA
duplex, and antibacterial activity has been evaluated. Bisbenzimidazoles with
alkynyl side chains display excellent E. coli DNA topoisomerase I inhibition
properties with IC50 values <5.0 MUM. Several bisbenzimidazoles (3, 6, 7, 8) also
inhibit RNA topoisomerase activity of E. coli DNA topoisomerase I.
Bisbenzimidazoles inhibit bacterial growth much better than monobenzimidazoles
for Gram-positive strains. The minimum inhibitory concentration (MIC) was much
lower for Gram positive bacteria (Enterococcus spp. and Staphylococcus spp.,
including two MRSA strains 0.3-8 MUg/mL) than for the majority of Gram negative
bacteria (Pseudomonas aeruginosa, 16-32 MUg/mL, Klebsiella pneumoniae > 32
MUg/mL). Bisbenzimidazoles showed varied stabilization of B-DNA duplex (1.2-23.4
degrees C), and cytotoxicity studies show similar variation dependent upon the
side chain length. Modeling studies suggest critical interactions between the
inhibitor side chain and amino acids of the active site of DNA topoisomerase I.
PMID- 28513178
TI - Decoupling the Effects of Mass Density and Hydrogen-, Oxygen-, and Aluminum-Based
Defects on Optoelectronic Properties of Realistic Amorphous Alumina.
AB - The search for functional materials is currently hindered by the difficulty to
find significant correlation between constitutive properties of a material and
its functional properties. In the case of amorphous materials, the diversity of
local structures, chemical composition, impurities and mass densities makes such
a connection difficult to be addressed. In this Letter, the relation between
refractive index and composition has been investigated for amorphous AlOx
materials, including nonstoichiometric AlOx, emphasizing the role of structural
defects and the absence of effect of the band gap variation. It is found that the
Newton-Drude (ND) relation predicts the refractive index from mass density with a
rather high level of precision apart from some structures displaying structural
defects. Our results show especially that O- and Al-based defects act as additive
local disturbance in the vicinity of band gap, allowing us to decouple the mass
density effects from defect effects (n = n[ND] + Deltandefect).
PMID- 28513179
TI - Consumption of Watermelon Juice Enriched in l-Citrulline and Pomegranate
Ellagitannins Enhanced Metabolism during Physical Exercise.
AB - l-Citrulline is a nonessential amino acid precursor of arginine and indirectly a
precursor of nitric oxide (NO), which is a vasodilator and increases
mitochondrial respiration. On the other hand, the antioxidant pomegranate
ellagitannins are precursors of urolithin A, which has been associated with
mitophagy and increased muscle function. To elucidate if a single dose of
watermelon enrichment with these compounds could have a positive effect after
high-intensity exercise (eight sets of eight repetitions of half-squat exercise),
a double-blind randomized crossover in vivo study was performed in healthy male
subjects (n = 19). Enrichment juices maintained basal levels of blood markers of
muscle damage, such as lactate dehydrogenase and myoglobin, and showed a
significant maintenance of force during the exercise and a significant decrease
in the rating of perceived exertion and muscle soreness after exercise. A
positive effect was observed between l-citrulline and ellagitannins, improving
the ergogenic effect of watermelon juice.
PMID- 28513180
TI - Infrared Spectra of Neutral Bent Carbon Dioxide.
AB - A combined ab initio and quantum dynamical study characterizes a family of bent
neutral carbon dioxide molecules in terms of their vibrational levels, electric
dipole moment surfaces, and infrared spectra in the gas phase. The considered
isomers include the dioxiranylidene form of CO2 with the equilibrium valence
angle of 72 degrees , belonging to the ground electronic state, and four open
structures with the valence angles of 118 degrees /119 degrees (they belong to
the singlet and triplet electronic states 21A' and 13A', respectively) and 127
degrees /128 degrees (states 11A" and 13A", respectively). All studied bent
structures possess permanent dipole moments. For all isomers, the antisymmetric
stretch fundamental is the strongest infrared transition. Individual bent
molecules can be distinguished on the basis of strong absorption bands in the
frequency window 1100-1800 cm-1 as well as isotopic shifts in the progression of
antisymmetric stretch mode. Excitation of bent neutral carbon dioxide near a
perfect metal surface is also briefly discussed. It is argued that the excitation
energy from the linear ground state exhibits a substantial red shift depending on
the molecule-metal distance.
PMID- 28513181
TI - Synthesis of [8]Cycloparaphenylene-octacarboxylates via Rh-Catalyzed Stepwise
Cross-Alkyne Cyclotrimerization.
AB - The synthesis of C4- and C2-symmetrical [8]cycloparaphenylene (CPP)
octacarboxylates has been achieved via macrocyclization by the rhodium-catalyzed
intermolecular stepwise cross-cyclotrimerization and subsequent reductive
aromatization. The C4-symmetrical octa-tert-butyl [8]CPP-octacarboxylate forms a
dimer in which eight ester moieties face each other. The dimers are aligned so as
to make a one-dimensional column with a channel structure inside. Both absorption
and fluorescence maxima of [8]CPP-octacarboxylates in CHCl3 were significantly
blue-shifted compared to those of [8]CPP due to the presence of eight electron
withdrawing ester moieties.
PMID- 28513182
TI - 'It just opens up their world': autism, empathy, and the therapeutic effects of
equine interactions.
AB - Experiences of autism-spectrum disorder are now increasingly studied by social
scientists. Human-animal relations have also become a major focus of social
inquiry in recent years. Examining horse-assisted therapy for autistic spectrum
disorders, this is the first paper that brings these fields together. Drawing on
participant observation and interviews at a UK horse therapy Centre, this article
examines how staff and the parents of riders account for the successes and
limitations of equine therapy. To the respondents, horses 'open up' autistic
children and make possible interactions that seemed impossible before. Horses
were regarded as facilitating the emergence of apparently social behaviours,
which included eye contact, pointing, and speech. Three key explanations emerged
for therapeutic success: the sensorial, embodied experience of riding the horse;
the specific movements and rhythms of the horse; and, the 'personality' of the
horse. Equine therapy can be regarded as enabling a form of multispecies
intersubjectivity, with the resonance between rider and horse seeming to make
possible a new attunement between humans. Practices of equine therapy, and
perceptions of its efficacy, serve in turn to attune social scientists to a
version of empathy constituted through lively and sensorial interactions, as
opposed to one that is restricted to particular kinds of humans.
PMID- 28513183
TI - Design and statistical analysis of method transfer studies for biotechnology
products.
PMID- 28513185
TI - Moderate dementia: relational social engagement (RSE) during family visits.
AB - OBJECTIVE: This qualitative study seeks evidence of retained social awareness in
individuals with moderate dementia residing in care-homes, when engaged in
interactive family visits. METHOD: Speech/non-speech data collected from 10/15
minute video-recorded family interactions of five family groups (12 individuals;
2 sessions per family group) were coded using thematic analysis. RESULTS:
Interactional patterns embedded in familiar bonds provided the context for the
superordinate theme: relational social engagement (RSE). This overarched two
subthemes: in-step and out-of-step; highlighting that RSE, can occur as a result
of both positive and negative familial communication patterns. When familial
communication was in-step, despite changed communication pathways, the resident's
attempts at social engagement appeared open, relaxed, and responsive. A sense of
trust, and familiarity appeared to facilitate reciprocal understanding and the
striving of resident family members to retain family group membership. When
familial communication was out-of-step, active attempts at reciprocity or open
engagement from visiting family members were not observed. At such times,
communication became discordant, and frustrated in their efforts to remain an
integral part of the family group, the resident appeared disinterested or guarded
often retorting with annoyance at visiting family members. CONCLUSION: The
construct of RSE appears specific to prior meaningful relationships, where
optimal social awareness and communication, positive and negative, can occur.
Currently, dementia assessment and care does not include RSE during family
interactions. Implications are discussed.
PMID- 28513186
TI - Initially intact neural responses to pain in autism are diminished during
sustained pain.
AB - Pain assessments typically depend on self-report of the pain experience. Yet, in
individuals with autism spectrum disorders, this can be an unreliable due to
communication difficulties. Importantly, observations of behavioral hypo- and
hyperresponsivity to pain suggest altered pain sensitivity in autism spectrum
disorder. Neuroimaging may provide insight into mechanisms underlying pain
behaviors. The neural pain signature reliably responds to painful stimulation and
is modulated by other outside regions, affecting the pain experience. In this
first functional magnetic resonance imaging study of pain in autism spectrum
disorder, we investigated neural responses to pain in 15 adults with autism
spectrum disorder relative to a typical comparison group (n = 16). We explored
temporal and spatial properties of the neural pain signature and its modulators
during sustained heat pain. The two groups had indistinguishable pain ratings and
neural pain signature responses during acute pain; yet, we observed strikingly
reduced neural pain signature response in autism spectrum disorder during
sustained pain and after stimulus offset. The posterior cingulate cortex, a
neural pain signature modulating region, mirrored this late signal reduction in
autism spectrum disorder. Intact early responses, followed by diminished late
responses to sustained pain, may reflect altered pain coping or evaluation in
autism spectrum disorder. Evidence of a dichotomous neural response to initial
versus protracted pain may clarify the coexistence of both hypo- and
hyperresponsiveness to pain in autism spectrum disorder.
PMID- 28513187
TI - Stress and Response to Treatment: Insights From a Pilot Study Using a 4-week
Contemplative Self-Healing Meditation Intervention for Posttraumatic Stress in
Breast Cancer.
AB - Along with symptoms of anxiety and depression, many breast cancer survivors
experience symptoms of posttraumatic stress disorder (PTSD) that may worsen in
the setting of other stressful life events. The aim of this pilot study was to
evaluate whether a 4-week version of our Contemplative Self-Healing program would
have different effects in reducing PTSD symptoms between breast cancer survivors
with or without chronic stress at baseline. PTSD symptoms were measured using the
Impact of Events scale (IES). A linear mixed model analysis was used to evaluate
within patients changes in IES score. Results showed that breast cancer patients
who were experiencing chronic stress reported greater improvement in IES score
than those without chronic stress. Our preliminary findings shed light on the
need to evaluate life stressors in breast cancer patients. Evaluating chronic
stress may be essential in predicting which cancer patients may benefit most from
a psychological intervention.
PMID- 28513188
TI - Late presentation of esophageal rupture following blunt thoracic trauma.
AB - Esophageal rupture following blunt thoracic trauma is extremely rare. A 30-year
old man sustained a road traffic accident causing blunt thoracic trauma that
resulted in lower esophageal rupture. He presented 24 h after the initial trauma
and was managed with primary repair and aggressive lavage with a drainage
procedure. Early identification and repair of esophageal rupture is vital for
preventing mediastinitis, but an aggressive surgical and postoperative management
strategy can prevent mortality even in late presentations.
PMID- 28513189
TI - Transcatheter aortic valve implantation: the transaortic approach.
AB - Background Transcatheter aortic valve implantation has been established as a safe
and effective treatment option for patients at high or prohibitive surgical risk.
However, some patients may not be suitable for the transfemoral approach due to
severe iliofemoral disease or aneurysmal disease of the thoracoabdominal aorta.
The aim of this case series was to evaluate the feasibility and clinical outcomes
of the transaortic approach. Methods From May 2015 to June 2016, 5 patients (mean
age 78.4 +/- 3.9 years) with severe symptomatic aortic stenosis underwent
transaortic transcatheter aortic valve implantation after a heart team
discussion. They were considered to be at high surgical risk and ineligible for
the transfemoral approach due to iliofemoral or thoracoabdominal aortic disease.
Results A CoreValve Evolut R was successfully deployed in all 5 patients. We
performed 4 right mini-parasternal incisions and one J-incision partial
sternotomy. None of the patients required permanent pacemaker implantation, one
required reopening of the mini-parasternal incision for postoperative bleeding.
Follow-up echocardiography one month after the procedure showed improvement in
the mean aortic gradient (from 63.2 to 8.3 mm Hg) and aortic valve area (from
0.62 to 2.2 cm2). None of the patients had more than mild paravalvular leakage.
There was no intraoperative or 30-day mortality. Conclusion Transaortic
transcatheter aortic valve implantation is a safe and feasible option for
patients with severe aortic stenosis who are considered unsuitable for
transfemoral aortic valve implantation.
PMID- 28513190
TI - Prevalence and correlates of bullying victimisation and perpetration in a
nationally representative sample of Australian youth.
AB - OBJECTIVE: Bullying prevalence studies are limited by varied measurement methods
and a lack of representative samples. This study estimated the national
prevalence of bullying victimisation, perpetration and combined victim
perpetration experiences in a representative population-based sample of
Australian youth. The relationships between the three types of bullying
involvement with a range of mental health symptoms and diagnoses were also
examined. METHODS: A randomly selected nationally representative sample aged 11
17 years ( N = 2967, Mage = 14.6 years; 51.6% male) completed the youth component
of the Second Australian Child and Adolescent Survey of Mental Health and
Wellbeing (Young Minds Matter). Parents or carers also completed a structured
face-to-face interview that asked questions about a single randomly selected
child in the household. The youth survey comprised self-reported bullying
victimisation and perpetration (Olweus Bully-Victim Questionnaire-adapted),
psychological distress (K10), emotional and behavioural problems (Strengths and
Difficulties Questionnaire), as well as self-harm, suicide attempts and substance
use. Modules from the Diagnostic Interview Schedule for Children Version IV were
administered to all youth and parents to assess for mental disorder diagnoses
(major depressive disorder, any anxiety disorder and any externalising disorder
[attention-deficit hyperactivity disorder, oppositional defiant disorder and
conduct disorder]). RESULTS: The 12-month prevalence of bullying victimisation
was 13.3%, perpetration 1.6% and victim-perpetration 1.9%. Logistic regression
models showed all forms of involvement in bullying were associated with increased
risk of psychological distress, emotional and behavioural problems, substance
use, self-harm and attempted suicide. Victimisation and victim-perpetration were
associated with youth-reported major depressive disorder. There were also
significant associations between bullying involvement and parent-reported
diagnoses of major depressive disorder, any anxiety disorder and any
externalising disorder. CONCLUSION: Bullying continues to be frequently
experienced by Australian adolescents. The current findings showed that
involvement in any bullying behaviour was associated with increased risk of
concurrent mental health problems. This evidence can be used to inform decisions
concerning the allocation of resources to address this important health issue.
PMID- 28513191
TI - The antecedents and outcomes of dyadic coping in close personal relationships: a
systematic review and narrative synthesis.
AB - BACKGROUND AND OBJECTIVES: Theories of dyadic coping and empirical literature
have intermittently and inconsistently highlighted antecedents and outcomes of
dyadic coping. The purpose of this review was to systematically identify the
antecedents and outcomes of dyadic coping in close personal relationships.
DESIGN: A PRISMA-guided systematic review and narrative synthesis. METHODS:
Literature searches were conducted using CINAHL, PubMed, PsycINFO, and citation
pearl growing to identify studies that were relevant to the aim of the review.
The search strategy and exclusion criteria led to a final sample of 46 studies
that each highlighted antecedents and outcomes of dyadic coping among married
couples. Each study was critically appraised and analyzed using narrative
synthesis. RESULTS: The narrative synthesis highlighted five antecedents
(learning, gender, relationship characteristics, relationship role, and cultural
influences) and two outcomes (relationship functioning and personal health) of
dyadic coping. CONCLUSION: The review exposes inconsistencies in the
conceptualization of dyadic coping, highlights a range of antecedents that
influence dyadic coping, and suggests that dyadic coping can have positive
benefits for relationship functioning and personal health. The findings have
implications for future research and practice (e.g. when working with couples to
improve relationship functioning).
PMID- 28513192
TI - The haemodynamic effect of an adjustable band in an arteriovenous fistula.
AB - A number of treatment approaches exist for excessive flowrate arteriovenous
fistulae. Banding has a number of advantages, yet there is concern over its use
due to reported high post-surgery thrombosis rates. A computational study is
conducted of a new technique, to elucidate the hemodynamics present in the
process. The key improvement involves the use of an adjustable band which can be
used to optimise the flowrate during the surgery. The pressure and flowrate
changes are apparent from the computational results and the computational results
also demonstrate that further optimization may be possible. We then present a
small cohort of five cases where the new banding procedure has been implemented
with success. The new technique was combined with intra-operative ultrasound flow
monitoring.
PMID- 28513193
TI - Impact of Health Literacy on Time Spent Seeking Hand Care.
AB - BACKGROUND: Patients with limited health literacy may have less knowledge and
fewer resources for efficient access and navigation of the health care system. We
tested the null hypothesis that there is no correlation between health literacy
and total time spent seeking hand surgery care. METHODS: New patients visiting a
hand surgery clinic at a suburban academic medical center were asked to complete
a questionnaire to determine demographics, total time spent seeking hand surgery
care, and outcomes. A total of 112 patients were included in this study. RESULTS:
We found health literacy levels did not correlate with total time seeking hand
surgery care or from booking an appointment to being evaluated in clinic.
CONCLUSIONS: In this suburban academic medical center, patients with low health
literacy do not spend more time seeking hand surgery care and do have longer
delays between seeking and receiving care. The finding that-at least in this
setting-health literacy does not impact patient time seeking hand care suggests
that resources to improve health disparities can be focused elsewhere in the care
continuum.
PMID- 28513195
TI - Binge drinking: Health impact, prevalence, correlates and interventions.
AB - OBJECTIVE: Binge drinking (also called heavy episodic drinking, risky single
occasion drinking etc.) is a major public health problem. This paper provides an
overview of recently published evidence concerning the definition and
measurement, prevalence rates, health impact, demographic and psychosocial
correlates of, and interventions for, binge drinking. DESIGN: Narrative review.
RESULTS: Mostly occurring among young people at weekends, binge drinking
increases the risk of both acute (e.g. injuries) and long-term negative
consequences (e.g. alcohol disorders). Binge drinkers tend to be extrovert,
impulsive and sensation-seeking. Stress, anxiety, traumatic events and depression
are also related to binge drinking. Both alcohol-related behaviour of parents and
general parenting (e.g. parenting styles, monitoring) are also important. Other
major risk factors for binge drinking are frequently spending time with friends
who drink, and the drinking norms observed in the wider social environment (e.g.
school, community, culture). Emergency departments, birthday parties,
fraternities and the workplace serve as settings for interventions; these are
increasingly delivered via digital and mobile technology. There is evidence of
small-sized effects across approaches (brief interventions, personalised
normative feedback, protective behavioural strategies etc.) and populations.
CONCLUSION: A more consistent terminology, investigating multi-level influences
and identifying the most effective intervention components are challenges for
future research.
PMID- 28513194
TI - Long noncoding RNAs: emerging regulators of tumor angiogenesis.
AB - Long noncoding RNAs (lncRNAs) participate in multiple biological processes
especially human diseases, of which, tumor seems to be one of the most
significant. Angiogenesis has been deemed to have a pivotal role in a series of
tumor biological behaviors in tumorigenesis, progression and prognosis. Emerging
evidences suggested that lncRNAs are involved in tumor angiogenesis and lncRNAs
have already been verified to be potential biomarkers and promising therapeutic
targets. This review summarized emerging angiogenesis-related lncRNAs, discussed
their mechanisms interacting with cytokines, cancer stem cells, miRNAs and tumor
hypoxia microenvironment, and demonstrated if lncRNAs could be new candidate
targets of antiangiogenesis therapy.
PMID- 28513196
TI - Synthesis and in vivo antimalarial activity of novel naphthoquine derivatives
with linear/cyclic structured pendants.
AB - AIM: Naphthoquine (NQ) was discovered by our institute as an antimalarial
candidate in 1980s, and currently employed as an artemisinin-based combination
therapy partner drug. Resistance to NQ was found in mouse model in laboratory,
and might emerge in future as widely used. METHODOLOGY: We herein report the
design and synthesis of NQ derivatives by replacing t-butyl moiety with
linear/cyclic structured pendants. All the target compounds 6a-l and
intermediates 5a-h were tested for their in vivo antimalarial activity against
Plasmodium berghei K173 strain in mice. RESULTS: Compounds 6a and 6j were found
to have a comparable or slightly more potent activity (the 50% effective dose
[ED50], which is required to decrease parasitemia by 50%: 0.38-0.43 mg/kg) than
NQ (ED50: 0.48 mg/kg). CONCLUSION: The newly designed compounds 6a and 6j might
be promising antimalarial candidates for further research.
PMID- 28513197
TI - Uptake of telehealth implementation for COPD patients in a high-poverty, inner
city environment: A survey.
AB - This study aimed to investigate computer and internet access and education
attained in patients with chronic obstructive pulmonary disease (COPD) as
potential barriers to implementation of telemedicine. We prospectively assessed
98 patients admitted with an acute exacerbation of COPD (mean age: 70.5 +/- 9.3
years; force expired volume in the first second: 0.75 +/- 0.39 L; 59% male)
recording educational level attained and home computer and internet access.
Hospital readmission surveillance occurred up to 2.7 (2.6-2.8) years following
the index hospital admission. Only 16% of patients had a computer and only 14%
had internet access; this group were younger and more educated than those without
a computer. There was no difference in hospital readmissions over 2 years between
those with and without access to a computer or internet. Only 12% of the whole
cohort were educated to a school leaving age of 16 years and this group were more
likely to be still working. School leaving age was directly associated with fewer
hospital readmissions ( r = 0.251, p = 0.031). In conclusion, these data
highlight the current challenges to the widespread implementation of telehealth
in COPD patients as there is limited availability of computer and internet access
with such patients demonstrating a lower level of education achievement.
PMID- 28513199
TI - Experience of exclusion: A framework analysis of socioeconomic factors affecting
cardiac rehabilitation participation among patients with acute coronary syndrome.
AB - BACKGROUND: The Danish public healthcare system provides comprehensive care based
on the principle of equal access. However, it is well documented that patients
with low socioeconomic position are less likely to participate in cardiac
rehabilitation. More knowledge is needed to understand this phenomenon. The aim
of the study was to explore the patient experience of barriers to completion of
phase II cardiac rehabilitation, and to investigate the impact of socioeconomic
factors on completion of cardiac rehabilitation. METHODS: The study had a
qualitative explorative design using semi-structured individual or dyadic
interviews with patients ( n = 24) and close relatives ( n = 12). Informants were
sampled from a quantitative prospective study of 302 patients with acute coronary
syndrome and data were analyzed using the framework method. RESULTS: Patients in
different socioeconomic groups were challenged by a rigid and non-individualized
rehabilitation program. A total of five themes were identified that might explain
non-participation in cardiac rehabilitation: exclusion by time and place,
exclusion by health beliefs, exclusion from counseling, exclusion by alienation,
and exclusion of relatives. The themes were described in a matrix of
socioeconomic factors of age, sex, education and employment. CONCLUSIONS:
Patients in various socioeconomic subgroups felt excluded from cardiac
rehabilitation for different reasons. This study supports earlier findings and
provides examples of real-life issues that need to be addressed to prevent
attrition and encourage participation. Equal access to cardiac rehabilitation can
only be reached if the physical and psychological needs of patient and family are
met by tailoring therapy to consider age, sex, education and employment groups.
PMID- 28513198
TI - Cleaning and infection control of airway clearance devices used by CF patients.
AB - Respiratory treatment for cystic fibrosis (CF) patients includes use of
respiratory devices. Contamination of airway clearance devices has not been
adequately explored. We aimed to determine whether airway clearance devices are
contaminated after use and whether cleaning guidelines for nebulizers are as
effective for airway clearance devices. Patients brought their airway clearance
devices to the clinic. Swabs from the devices were taken before and after
cleaning and were cultured for bacterial counts. Total colony-forming units (CFU)
was determined, and predominant colonies were identified using Matrix-Assisted
Laser Desorption Ionization Time-of-Flight Mass Spectrometry technology. Thirty
devices were collected from 23 patients. Most of the devices (28/30) were
contaminated when brought to the clinic. Complete bacterial eradication was
achieved in 15 (50%) samples and partial eradication in 9 (30%). The cleaning was
totally ineffective in four samples. Median CFU decreased significantly from 1250
(IQR 25-75% 175-10.000) to 0 (IQR 25-75% 0-700) before and after cleaning ( p <
0.0001). The predominant organisms were identified in five samples only, and
there was no concordance with sputum culture results. Airway clearance devices
are contaminated after use, and appropriate cleaning can reduce contamination.
The effect on disease progression in CF patients is unclear. There is a need for
infection prevention and control guidelines for the growing number of respiratory
devices.
PMID- 28513201
TI - Real-World Evolution of Robot Morphologies: A Proof of Concept.
AB - Evolutionary robotics using real hardware has been almost exclusively restricted
to evolving robot controllers, but the technology for evolvable morphologies is
advancing quickly. We discuss a proof-of-concept study to demonstrate real robots
that can reproduce. Following a general system plan, we implement a robotic
habitat that contains all system components in the simplest possible form. We
create an initial population of two robots and run a complete life cycle,
resulting in a new robot, parented by the first two. Even though the individual
steps are simplified to the maximum, the whole system validates the underlying
concepts and provides a generic workflow for the creation of more complex
incarnations. This hands-on experience provides insights and helps us elaborate
on interesting research directions for future development.
PMID- 28513202
TI - Abstraction, Sensory-Motor Coordination, and the Reality Gap in Evolutionary
Robotics.
AB - One of the major challenges of evolutionary robotics is to transfer robot
controllers evolved in simulation to robots in the real world. In this article,
we investigate abstraction of the sensory inputs and motor actions as a tool to
tackle this problem. Abstraction in robots is simply the use of preprocessed
sensory inputs and low-level closed-loop control systems that execute higher
level motor commands. To demonstrate the impact abstraction could have, we
evolved two controllers with different levels of abstraction to solve a task of
forming an asymmetric triangle with a homogeneous swarm of micro air vehicles.
The results show that although both controllers can effectively complete the task
in simulation, the controller with the lower level of abstraction is not
effective on the real vehicle, due to the reality gap. The controller with the
higher level of abstraction is, however, effective both in simulation and in
reality, suggesting that abstraction can be a useful tool in making evolved
behavior robust to the reality gap. Additionally, abstraction aided in reducing
the computational complexity of the simulation environment, speeding up the
optimization process. Preeminently, we show that the optimized behavior exploits
the environment (in this case the identical behavior of the other robots) and
performs input shaping to allow the vehicles to fly into and maintain the
required formation, demonstrating clear sensory-motor coordination. This shows
that the power of the genetic optimization to find complex correlations is not
necessarily lost through abstraction as some have suggested.
PMID- 28513200
TI - HIV-infected individuals who use alcohol and other drugs, and virologic
suppression.
AB - People living with HIV (PLWH) on antiretroviral therapy (ART) who use substances
were examined to (a) describe those with virologic control and (b) determine
which substance use-factors are associated with lack of virologic control.
Participants were adult PLWH taking ART with either past 12-month DSM-IV
substance dependence or past 30-day alcohol or illicit drug use. Substance use
factors included number of DSM-IV alcohol or drug dependence criteria and past 30
day specific substance use. Associations with HIV viral load (HVL) (<200 vs.
>=200 copies/mL) were tested using logistic regression models. Multivariable
analyses adjusted for age, sex, homelessness and anxiety or depression.
Participants (n = 202) were median age 50 years, 66% male, 51% African American
and 75% self-reported >=90% past 30-day ART adherence. Though HVL suppression
(HVL <200 copies/mL) was achieved in 78% (158/202), past 30-day substance use was
common among this group: 77% cigarette use; 51% heavy alcohol use; 50% marijuana;
27% cocaine; 16% heroin; and 15% illicit prescription opioid use. After adjusting
for covariates, specific substance use was not associated with a detectable HVL,
however number of past 12-month DSM-IV drug dependence criteria was (adjusted
odds ratio = 1.23 for each additional criterion, 95% CI: 1.04-1.46). Three
quarters of a substance-using cohort of PLWH receiving ART had virologic control
and >=90% ART adherence. Substance dependence criteria (particularly drug
dependence), not specifically substance use, were associated with lack of
virologic control. Optimal HIV outcomes can be achieved by individuals who use
alcohol or drugs and addressing symptoms of substance dependence may improve HIV
related outcomes.
PMID- 28513203
TI - Automating the Incremental Evolution of Controllers for Physical Robots.
AB - Evolutionary robotics is challenged with some key problems that must be solved,
or at least mitigated extensively, before it can fulfill some of its promises to
deliver highly autonomous and adaptive robots. The reality gap and the ability to
transfer phenotypes from simulation to reality constitute one such problem.
Another lies in the embodiment of the evolutionary processes, which links to the
first, but focuses on how evolution can act on real agents and occur
independently from simulation, that is, going from being, as Eiben, Kernbach, &
Haasdijk [2012, p. 261] put it, "the evolution of things, rather than just the
evolution of digital objects...." The work presented here investigates how fully
autonomous evolution of robot controllers can be realized in hardware, using an
industrial robot and a marker-based computer vision system. In particular, this
article presents an approach to automate the reconfiguration of the test
environment and shows that it is possible, for the first time, to incrementally
evolve a neural robot controller for different obstacle avoidance tasks with no
human intervention. Importantly, the system offers a high level of robustness and
precision that could potentially open up the range of problems amenable to
embodied evolution.
PMID- 28513204
TI - On Design Mining: Coevolution and Surrogate Models.
AB - Design mining is the use of computational intelligence techniques to iteratively
search and model the attribute space of physical objects evaluated directly
through rapid prototyping to meet given objectives. It enables the exploitation
of novel materials and processes without formal models or complex simulation. In
this article, we focus upon the coevolutionary nature of the design process when
it is decomposed into concurrent sub-design-threads due to the overall complexity
of the task. Using an abstract, tunable model of coevolution, we consider
strategies to sample subthread designs for whole-system testing and how best to
construct and use surrogate models within the coevolutionary scenario. Drawing on
our findings, we then describe the effective design of an array of six
heterogeneous vertical-axis wind turbines.
PMID- 28513205
TI - Introduction to the Evolution of Physical Systems Special Issue.
PMID- 28513206
TI - A General Architecture for Robotics Systems: A Perception-Based Approach to
Artificial Life.
AB - Departing from the conventional view of the reasons for the behavior of living
systems, this research presents a radical and unique view of that behavior, as
the observed side effects of a hierarchical set of simple, continuous, and
dynamic negative feedback control systems, by way of an experimental model
implemented on a real-world autonomous robotic rover. Rather than generating
specific output from input, the systems control their perceptual inputs by
varying output. The variables controlled do not exist in the environment, but are
entirely internal perceptions constructed as a result of the layout and
connections of the neural architecture. As the underlying processes are
independent of the domain, the architecture is universal and thus has significant
implications not only for understanding natural living systems, but also for the
development of robotics systems. The central process of perceptual control has
the potential to unify the behavioral sciences and is proposed as the missing
behavioral principle of Artificial Life.
PMID- 28513207
TI - Evolutionary Developmental Robotics: Improving Morphology and Control of Physical
Robots.
AB - Evolutionary algorithms have previously been applied to the design of morphology
and control of robots. The design space for such tasks can be very complex, which
can prevent evolution from efficiently discovering fit solutions. In this article
we introduce an evolutionary-developmental (evo-devo) experiment with real-world
robots. It allows robots to grow their leg size to simulate ontogenetic
morphological changes, and this is the first time that such an experiment has
been performed in the physical world. To test diverse robot morphologies, robot
legs of variable shapes were generated during the evolutionary process and
autonomously built using additive fabrication. We present two cases with evo-devo
experiments and one with evolution, and we hypothesize that the addition of a
developmental stage can be used within robotics to improve performance. Moreover,
our results show that a nonlinear system-environment interaction exists, which
explains the nontrivial locomotion patterns observed. In the future, robots will
be present in our daily lives, and this work introduces for the first time
physical robots that evolve and grow while interacting with the environment.
PMID- 28513208
TI - Self-Organization of Vocabularies under Different Interaction Orders.
AB - Traditionally, the formation of vocabularies has been studied by agent-based
models (primarily, the naming game) in which random pairs of agents negotiate
word-meaning associations at each discrete time step. This article proposes a
first approximation to a novel question: To what extent is the negotiation of
word-meaning associations influenced by the order in which agents interact?
Automata networks provide the adequate mathematical framework to explore this
question. Computer simulations suggest that on two-dimensional lattices the
typical features of the formation of word-meaning associations are recovered
under random schemes that update small fractions of the population at the same
time; by contrast, if larger subsets of the population are updated, a periodic
behavior may appear.
PMID- 28513210
TI - Alzheimer Europe's position on involving people with dementia in research through
PPI (patient and public involvement).
AB - This paper reflects Alzheimer Europe's position on PPI (patient and public
involvement) in the context of dementia research and highlights some of the
challenges and potential risks and benefits associated with such meaningful
involvement. The paper was drafted by Alzheimer Europe in collaboration with
members of INTERDEM and the European Working Group of People with Dementia. It
has been formally adopted by the Board of Alzheimer Europe and endorsed by the
Board of INTERDEM and by the JPND working group 'Dementia Outcome Measures -
Charting New Territory'. Alzheimer Europe is keen to promote the involvement of
people with dementia in research, not only as participants but also in the
context of PPI, by generating ideas for research, advising researchers, being
involved in consultations and being directly involved in research activities.
This position paper is in keeping with this objective. Topics covered include,
amongst others, planning involvement, establishing roles and responsibilities,
training and support, managing information and input from PPI, recognising the
contribution of people with dementia involved in research in this way, promoting
and protecting the rights and well-being of people with dementia, training and
support, and promoting an inclusive approach and the necessary infrastructure for
PPI in dementia research.
PMID- 28513209
TI - Caregiver determinants of patient clinical event risk in heart failure.
AB - BACKGROUND: Preventing hospitalization and improving event-free survival are
primary goals of heart failure (HF) treatment according to current European
Society of Cardiology guidelines; however, substantial uncertainty remains in our
ability to predict risk and improve outcomes. Although caregivers often assist
patients to manage their HF, little is known about their influence on clinical
outcomes. AIMS: To quantify the influence of patient and caregiver
characteristics on patient clinical event risk in HF. METHODS: This was a
secondary analysis of data using a sample of Italian adults with HF and their
informal caregivers ( n = 183 patient-caregiver dyads). HF patients were followed
over 12 months for the following clinical events: hospitalization for HF,
emergency room visit for HF or all-cause mortality. Influence of baseline
caregiver- and patient-level factors (patient and caregiver age; dyad
relationship type; patient New York Heart Association (NYHA) Class, cognition,
and comorbidities; and caregiver strain, mental health status, and contributions
to HF self-care) on patient risk of death or hospitalization/emergency room use
was quantified using Cox proportional hazards regression. RESULTS: Over the
course of follow up, 32.8% of patients died, 19.7% were hospitalized for HF and
10.4% visited the emergency room. Higher caregiver strain, better caregiver
mental health status and greater caregiver contributions to HF self-care
maintenance were associated with significantly better event-free survival. Worse
patient functional class and greater caregiver contributions to patient self-care
management were associated with significantly worse patient event-free survival.
CONCLUSION: Considering caregiving factors together with patient factors
significantly increases our understanding of patient clinical event risk in HF.
PMID- 28513211
TI - Image quality of low-radiation dose left atrial CT using filtered back projection
and an iterative reconstruction algorithm: intra-individual comparison in
unselected patients undergoing pulmonary vein isolation.
AB - Background Computed tomography (CT) of the left atrium (LA) is performed prior to
pulmonary vein isolation (PVI) to improve success of circumferential ablation for
atrial fibrillation. The ablation procedure itself exposes patients to
substantial radiation doses, therefore radiation dose reduction in pre-ablational
imaging is of concern. Purpose To assess and compare diagnostic performance of
low-radiation dose preprocedural CT in patients scheduled for PVI using two types
of reconstruction algorithms. Material and Methods Forty-six patients (61 +/- 10
years) scheduled for PVI were enrolled in this study irrespective of body-mass
index or cardiac rhythm at examination. An electrocardiographically triggered
dual-source CT scan was performed. Filtered back projection (FBP) and iterative
reconstruction (IR) algorithms were applied. Images were integrated into an
electroanatomic mapping (EAM) system. Subjective image quality was scored
independently by two readers on a five-point scale for both reconstruction
algorithms (1 = excellent to 5 = non-diagnostic). Signal-to-noise ratio (SNR),
contrast-to-noise ratio (CNR), and effective radiation dose were calculated.
Results Data acquisition and EAM integration were successful in all patients.
Median image quality score was 1 for both FBP (quartiles = 1, 1.62; range = 1-3)
and IR (quartiles = 1, 1.5; range = 1-3). Mean SNR was 7.61 +/- 2.14 for FBP and
9.02 +/- 2.69 for IR. Mean CNR was 5.92 +/- 1.80 for FBP and 6.95 +/- 2.29 for
IR. Mean effective radiation dose was 0.3 +/- 0.1 mSv. Conclusion At a radiation
dose of 0.3 +/- 0.1 mSv, high-pitch dual-source CT yields LA images of
consistently high quality using both FBP and IR. IR raises SNR and CNR without
significantly improving subjective image quality.
PMID- 28513213
TI - Remote Ischemic Conditioning: The Commercial Market? CellAegis Perspective.
AB - Remote ischemic conditioning (RIC) is at a pivotal point in its evolution, both
in terms of its adoption as a therapy and its viability commercially. The most
usual way of inducing RIC, with a standard blood pressure cuff and a stopwatch,
is time-consuming and potentially inaccurate and unsafe. Development of automated
devices have facilitated large-scale randomized trials and will make clinical
deployment of the technique more straightforward. Both the medical and commercial
future of RIC will depend on the results of upcoming phase 3 pivotal trials.
PMID- 28513212
TI - An Optical-Fiber-Based Smart Textile (Smart Socks) to Manage Biomechanical Risk
Factors Associated With Diabetic Foot Amputation.
AB - OBJECTIVE: This study aimed to validate a smart-textile based on fiber-optics for
simultaneous measurement of plantar temperature, pressure, and joint angles in
patients with diabetic peripheral neuropathy (DPN). METHODS: After in-vitro
validation in the laboratory, 33 eligible subjects with DPN were recruited (age:
58 +/- 8 years, BMI: 31.5 +/- 8 kg/m2) for assessing plantar pressure and
temperature during habitual gait-speed in a clinical-setting. All participants
were asked to walk at their habitual speed while wearing a pair of sensorized
socks made from highly flexible fiber optics (SmartSox). An algorithm was
designed to estimate temperature, pressure, and toe range of motion from optical
wavelength generated from SmartSox. To validate the device, results from thermal
stress response (TSR) using thermography and peak pressure measured by
computerized pressure insoles (F-Scan) were used as gold standards. RESULTS: In
laboratory and under controlled conditions, the agreements for parameters of
interest were excellent ( r > .98, P = .000), and no noticeable cross-talks
between measurements of temperature, angle, and pressure were observed. During
clinical data acquisition, a significant correlation was found for pressure
profile under different anatomical regions of interest between SmartSox and F
Scan ( r = .67, P < .050) as well as between thermography and SmartSox ( r = .55,
P < .050). CONCLUSION: This study demonstrates the validity of an innovative
smart textile for assessing simultaneously the key parameters associated with
risk of foot ulcers in patients with DPN. It may empower clinicians to
objectively stratify foot risk and provide timely care. Another study is
warranted to validate its clinical application in preventing limb threating
problems in patients with DPN.
PMID- 28513214
TI - The Future of Remote Ischemic Conditioning.
PMID- 28513215
TI - Presence of Air Trapping and Mosaic Attenuation on Chest Computed Tomography
Predicts Survival in Chronic Hypersensitivity Pneumonitis.
AB - RATIONALE: Significant heterogeneity of computed tomography (CT) presentation
exists within chronic hypersensitivity pneumonitis (HP). There are limited data
aimed at delineating the prognostic value of specific CT features, distribution,
and patterns in chronic HP. OBJECTIVES: To examine whether the presence of CT
mosaic attenuation (MA) and air trapping (AT), and the distribution or patterns
of fibrosis impact survival in subjects with chronic HP. METHODS: We
retrospectively identified 110 consecutively enrolled, well-characterized, biopsy
proven adult subjects with chronic HP between 1982 and 2015 from the National
Jewish Health interstitial lung disease research database. The first available CT
scan of diagnostic quality from each subject was formally evaluated for specific
CT findings associated with chronic HP and for overall CT pattern. A Cox
proportional hazards model was used to identify independent predictors in time-to
death analysis, and bootstrap analysis was performed for internal model
validation. RESULTS: Fibrotic HP (65%; 72/110) was most often peripheral in the
axial plane and lower lung preponderant. The distribution of lung disease in
those without fibrosis was most often axially and zonally diffuse. There was no
association between survival and CT distribution or CT pattern in the whole
cohort or within the fibrotic subset of subjects. After multivariate adjustment,
AT/MA was independently associated with survival in the whole cohort (HR = 0.26;
95% confidence interval = 0.07-0.97). Results were similar after restricting the
analyses to fibrotic HP cases. CONCLUSIONS: Among subjects with chronic HP, the
presence of CT AT/MA may identify subjects with better prognosis.
PMID- 28513216
TI - Efficacy of Syringe Filtration for the Selective Isolation of Campylobacter from
Chicken Carcass Rinse.
AB - We investigated the efficacy of syringe filtration for selective isolation of
Campylobacter from chicken carcass rinse by combining syringe filtration with the
conventional culture method. Whole chicken carcass rinses were incubated in
Bolton enrichment broth, set aside or subjected to syringe filtration, and
streaked on Campy-Cefex agar with or without cefoperazone antibiotic supplement.
Compared with the conventional method without filtration, 0.65-MUm-pore-size
syringe filtration resulted in a significantly higher number of Campylobacter
positive samples (23.8 to 37.5% versus 70.0 to 72.5%; P < 0.05), a lower number
of plates contaminated with non-Campylobacter (93.8% versus 6.3 to 26.3%), and a
lower growth index (1 = growth of a few colonies; 2 = growth of colonies on about
half of the plate; and 3 = growth on most of the plate) for competing microbiota
(2.9 to 3.0 versus 1.2 to 1.4). When syringe filtration was applied, agar plates
containing the antibiotic had significantly less contamination (6.3% versus
26.3%; P < 0.05) and a lower growth index (1.2 versus 1.4) compared with plates
without the antibiotic, although the Campylobacter isolation rate was similar (P
> 0.05). Syringe filtration combined with conventional enrichment improved the
rate and selectivity of Campylobacter isolation from chicken carcasses.
PMID- 28513217
TI - A Preliminary Study on the Effect of Computer-Aided Designed and Manufactured
Orthoses on Chronic Plantar Heel Pain.
AB - INTRODUCTION: Chronic plantar heel pain (CPHP) is a significant, painful
condition referring to a range of undifferentiated foot conditions that affect
the heel of the foot. METHOD: Participants presenting with CPHP of more than 6
months' duration were recruited on a first through the door basis. Computer-Aided
Design and Computer-Aided Manufactured (CAD-CAM) orthoses were designed and
constructed for each participant, then dispensed as per normal practice. Pre- and
postintervention assessment of pain was performed at baseline and after 6 weeks
of use, utilizing the pain subset of the Foot Function Index (FFI). RESULTS:
There was a significant reduction in the mean pain scores for all participants in
all constructs of the FFI. Total FFI score was also significant ( P = .003).
CONCLUSION: CAD-CAM orthoses have the potential to become a treatment modality of
choice in CPHP since they have resulted in a significant improvement in heel pain
after only 6 weeks' use. LEVELS OF EVIDENCE: Therapeutic, Level IV: Prospective,
comparative trial.
PMID- 28513218
TI - Three Cycles of Radiofrequency Ablation Are More Efficacious Than Two in the
Management of Morton's Neuroma.
AB - BACKGROUND: Morton's neuroma is a common cause of forefoot pain. Outcomes of
conservative therapy are mixed and many patients undergo operative intervention.
Radiofrequency ablation has recently gained favor as a treatment option, although
the optimal regime is unknown. This study investigates the effectiveness of 2
versus 3 cycles of radiofrequency ablation for the treatment of Morton's neuroma.
METHODS: We surveyed a cohort of patients with Morton's neuroma who had
progressed to radiofrequency ablation after failed conservative treatment.
Patients received either 2 or 3 cycles of radiofrequency ablation by a single
surgeon. We assessed patients based on their change in numerical pain rating
scale, symptom improvement, complications, and progression to surgical excision
through a series of telephone interviews. Outcomes between the 2 treatment arms
were compared by parametric tests. RESULTS: Twenty-eight patients were included
in the study. Eighteen patients with 21 neuromas received 2 cycles and 10
patients with 11 neuromas received 3 cycles. Mean time of follow-up was 12.9
months. Overall, 88% of patients were either very or moderately satisfied with
their outcome. In patients who received 2 cycles mean numerical pain scores
decreased from 7.9 +/- 1.1 to 3.4 +/- 2.4 postprocedure. Three patients
progressed to operative excision. In patients who received 3 cycles, numerical
pain scores decreased from 8.0 +/- 1.0 to 1.5 +/- 2.0 postprocedure. One patient
progressed to operative excision. Patients who received 3 cycles had reduced
medium-term pain postoperatively compared with 2 cycles (3.4 +/- 2.4 vs 1.5 +/-
2.0, P = .011). CONCLUSION: Radiofrequency ablation provides a high rate of
patient satisfaction in the treatment of Morton's neuroma with few side effects.
It appears that 3 cycles may be superior to 2 cycles but a randomized controlled
trial will be required to confirm these results. LEVELS OF EVIDENCE:
Intervention, Level III: Comparative study without concurrent controls.
PMID- 28513219
TI - A temporofrontal fascia flap that penetrated temporal muscle for the
reconstruction of an anterior skull base bone and dura: a technical case report.
AB - During skull base surgery, reconstruction of the dura is a very important
procedure. Here, the use of a temporofrontal pedicled fascia flap tunnelled
between temporal muscle fibres is described. This technique is easily performed
and has a low postoperative morbidity, including skin and temporal muscle
complications.
PMID- 28513220
TI - Corrigendum.
PMID- 28513221
TI - Sericins of mulberry and non-mulberry silkworms for eco-friendly synthesis of
silver nanoparticles.
AB - Green synthesis of silver nanoparticles (AgNPs) has received many interests as a
simple, cost-effective, and environmentally friendly method. This study reported
the use of sericins extracted from non-mulberry (Samia cynthia ricini) and
mulberry (Bombyx mori) silkworms for green syntheses of AgNPs. Both sericins
possessed the reducing activity, which the reducing activity of S. c. ricini
sericin was significantly higher than that of B. mori sericin. The formation of
AgNPs facilitated by S. c. ricini sericin was greater than B. mori sericin as
determined by the intensity of the surfacing plasmon resonance peak of silver at
412 nm. The synthesized AgNPs using both sericins were spherical and uniform in
size with the average diameter of ~13 nm. The silver component and the
crystalline structure was determined by energy-dispersive X-ray and X-ray
diffraction analyses. The synthesized AgNPs exhibited the antibacterial activity
against both Gram-positive Staphylococcus aureus and Gram-negative Escherichia
coli, suggesting their potential application as an effective antibacterial agent.
PMID- 28513222
TI - The contribution of CYP2C gene subfamily involved in epoxygenase pathway of
arachidonic acids metabolism to hypertension susceptibility in Russian
population.
AB - Numerous studies demonstrated an importance of cytochrome P-450 epoxygenase
pathway of arachidonic acids metabolism for the pathogenesis of essential
hypertension (EH). The present study was designed to investigate whether common
single-nucleotide polymorphisms (SNP) of CYP2C gene subfamily such as CYP2C8
(rs7909236 and rs1934953), CYP2C9 (rs9332242), and CYP2C19 (rs4244285) are
associated with susceptibility to EH in Russian population. A total of 816
unrelated Russian individuals comprising 425 EH patients and 391 normotensive
controls were included into the study. Genotyping of SNPs was performed using the
MassARRAY 4 system. SNP rs7909236 of CYP2C8 was significantly associated with
increased risk of EH (OR adjusted for sex and age was 2.99 95% CI 1.39-6.44, P =
0.005). SNPs rs1934953 CYP2C8 and rs4244285 of CYP2C19 showed association with EH
risk but at a borderline statistical significance (P <= 0.04). Combination of
genotypes CYP2C8 rs7909236 TT and CYP2C19 rs4244285 GG was associated with
increased EH risk (OR 3.34 95%CI 1.48-7.51, P = 0.004). Genotype-phenotype
correlation analysis showed that the levels of CYP2C8 mRNA were significantly
correlated with SNP rs7909236 (P = 0.01). in silico functional prediction
analysis revealed the functionality of majority of investigated SNPs. Thus, genes
of CYP2C subfamily are important genetic determinants of susceptibility to
essential hypertension in Russians.
PMID- 28513224
TI - Letter to the Editor.
PMID- 28513223
TI - Activation of thromboxane A2 receptors mediates endothelial dysfunction in
diabetic mice.
AB - BACKGROUND: Diabetes is one of high-risk factors for cardiovascular disease.
Improvement of endothelial dysfunction in diabetes reduces vascular
complications. However, the underlying mechanism needs to be uncovered. This
study was conducted to elucidate whether and how thromboxane A2 receptor (TPr)
activation contributes to endothelial dysfunction in diabetes. METHODS AND
RESULTS: Exposure of human umbilical vein endothelial cells (HUVECs) to either
TPr agonists, two structurally related thromboxane A2 (TxA2) mimetics,
significantly reduced phosphorylations of endothelial nitric oxide synthase
(eNOS) at Ser1177 and Akt at Ser473. These effects were abolished by
pharmacological or genetic inhibitors of TPr. TPr-induced suppression of eNOS and
Akt phosphorylation was accompanied by upregulation of PTEN (phosphatase and
tension homolog deleted on chromosome 10) and Ser380/Thr382/383 PTEN
phosphorylation. PTEN-specific siRNA restored Akt-eNOS signaling in the face of
TPr activation. The small GTPase, Rho, was also activated by TPr stimulation, and
pretreatment of HUVECs with Y27632, a Rho-associated kinase (ROCK) inhibitor,
rescued TPr-impaired Akt-eNOS signaling. In mice, streptozotocin-induced diabetes
was associated with aortic PTEN upregulation, PTEN-Ser380/Thr382/383
phosphorylation, and dephosphorylation of Akt (at Ser473) and eNOS (at Ser1177).
Importantly, administration of TPr antagonist blocked these changes. CONCLUSION:
We conclude that TPr activation impairs endothelial function by selectively
inactivating the ROCK-PTEN-Akt-eNOS pathway in diabetic mice.
PMID- 28513225
TI - Use of the augmentation index from applanation tonometry of the radial artery for
assessing the extent of coronary artery calcium as assessed by coronary computed
tomography.
AB - BACKGROUND: The augmentation index (AI) obtained from applanation tonometry of
the radial artery is technically the easiest and quickest of available methods
for assessing arterial stiffness. We tested the hypothesis that the radial AI is
associated with the extent of coronary artery calcium (CAC) as assessed by
coronary computed tomography (CCT). METHODS AND RESULTS: This study included 161
patients with known or suspected coronary artery disease undergoing central
hemodynamic measurements and CCT. Radial AI was recorded and was corrected in
accordance with heart rate (radial AI@75). Thirty-seven patients had no CAC (CAC
score = 0), 85 had low-grade CAC (CAC score = 1-399), and 39 had high-grade CAC
(CAC score >=400). Coronary risk factors, except for age and serum creatinine,
were similar among the three groups. There were significant differences in
brachial systolic blood pressure (SBP) (p = 0.011) and radial AI@75 (%) (p =
0.006). Multivariate analysis showed that age (beta = 0.27, p = 0.001), serum
creatinine (beta = 0.18, p = 0.03), and radial AI@75 (beta = 0.24, p = 0.005)
were significantly associated with ln (CAC score + 1), whereas brachial SBP was
not. Additionally, serum creatinine (odds ratio: 11.91, 95% confidence interval:
1.46-112.0, p = 0.02) and radial AI@75 (per 10%) (odds ratio: 1.76, 95%
confidence interval: 1.22-2.64, p = 0.002) were independent factors associated
with high-grade CAC. CONCLUSIONS: Our results suggest that the radial AI is
better for estimating CAC than brachial SBP in patients with known or suspected
coronary artery disease.
PMID- 28513226
TI - Application of proteomics to the study of Helicobacter pylori and implications
for the clinic.
AB - INTRODUCTION: Helicobacter pylori (H. pylori) is a gram-negative bacterium that
colonizes the gastric epithelium and mucous layer of more than half the world's
population. H. pylori is a primary human pathogen, responsible for the
development of chronic gastritis, peptic ulceration and gastric cancer.
Proteomics is impacting several aspects of medical research: understanding the
molecular basis of infection and disease manifestation, identification of
therapeutic targets and discovery of clinically relevant biomarkers. Areas
covered: The main aim of the present review is to provide a comprehensive
overview of the contribution of proteomics to the study of H. pylori infection
pathophysiology. In particular, we focused on the role of the bacterium and its
most important virulence factor, CagA, in the progression of gastric cells
transformation and cancer progression. We also discussed the proteomic approaches
aimed at the investigation of the host response to bacterial infection. Expert
commentary: In the field of proteomics of H. pylori, comprehensive analysis of
clinically relevant proteins (functional proteomics) rather than entire proteomes
will result in important medical outcomes. Finally, we provided an outlook on the
potential development of proteomics in H. pylori research.
PMID- 28513227
TI - Temporal Relationship of Sex Risk Behaviors and Substance Use Severity Among Men
in Substance Use Treatment.
AB - Sex risk behaviors and substance use are intertwined. Many men continue to engage
in high-risk sexual behaviors even when enrolled in substance use disorder (SUD)
treatment. We hypothesized that changes in sex risk behaviors would coincide with
changes in drug/alcohol use severity among men in SUD treatment. During an HIV
risk-reduction trial, men in methadone maintenance and outpatient drug-free
treatment (N = 359) completed assessments at baseline and six months after. We
assessed changes in sex risk and substance use severity, using the Addiction
Severity Index-Lite (ASI-Lite), controlling for treatment condition. In
multinomial logistic regressions, decreased alcohol severity was significantly
associated with decreases in reported sex partners, and increased alcohol
severity was significantly associated with increases in reported sex partners.
Increasing drug use severity was significantly associated with maintaining and
initiating sex with a high-risk partner, while decreasing alcohol use severity
was significantly associated with discontinuing sex under the influence. However,
changes in drug/alcohol use severity were not associated with changes in
unprotected sex. Substance use reductions may decrease HIV risk behaviors among
male substance users. Our findings highlight the importance of integrating
interventions in SUD treatment settings that address the intersection of sex risk
behaviors and substance use.
PMID- 28513228
TI - Relationship between CHOP/GADD153 and unstable human carotid atherosclerotic
plaque.
AB - BACKGROUND AND AIMS: The signaling protein C/EBP homologous protein (CHOP) and
corresponding growth-arrest-and-DNA-damage-inducible gene 153 (GADD153) is
associated with endoplasmic reticulum stress (ERS), which can lead to apoptosis.
Our study aims to elucidate the role of CHOP/GADD153 in unstable atherosclerotic
(AS) plaque formation isolated from confounding factors such as diabetes
mellitus, primary hyperlipidemia, autoimmune deficiencies/abnormalities,
essential hypertension, chronic heart failure, chronic kidney disease, and
smoking. MATERIAL AND METHODS: We collected carotid artery tissue samples from
patients aged 50-80 years-old who received carotid endarterectomies (CEA) at our
institution. We obtained fresh AS plaque samples during CEA and preserved the
specimens immediately in the operating room with liquid nitrogen. Samples were
categorized as stable or unstable AS plaques according to a six-stage histologic
classification. CHOP/GADD153 expression was then examined with
immunohistochemistry and reverse transcription polymerase chain reaction (RT
PCR). RESULTS: A total of 32 patients met our inclusion and exclusion criteria,
with 24 (75.0%) classified as unstable lesions. The mean optical density ratio
normalized to GAPDH for CHOP/GADD153 in stable and unstable groups was 0.357 +/-
0.025 and 0.490 +/- 0.027, respectively (p < .05). Positive immunostaining of
CHOP/GADD153 was found in macrophages and smooth muscle cells of unstable AS
plaques with a mean integrated optical density of 0.63 +/- 0.03, compared to 0.17
+/- 0.05 in the stable group (p < .05). CONCLUSIONS: In conclusion, we were able
to show significant elevation of CHOP/GADD153 in unstable plaques independent of
other confounding factors that induce ERS.
PMID- 28513229
TI - ABO blood group is a risk factor for coronary artery disease in patients with
poor blood pressure control.
AB - BACKGROUND: Few studies had examined the role of ABO blood groups on CAD in
hypertensive patients with different blood pressure (BP) controls. METHODS: A
total of 2708 patients with primary hypertension (HTN) were consecutively
enrolled and underwent coronary angiography (CAG) due to angina-like chest pain.
The severity of coronary artery stenosis was assessed by Gensini score (GS).
Patients were divided into two groups due to results of CAG: HTN with CAD (n =
2185) and HTN without CAD (n = 523). Poor BP control was defined as systolic BP
(SBP) >= mean in the study. Multivariable regression analysis was used to
determine the potential impact of ABO blood groups on risk of the presence and
severity of CAD. RESULTS: Compared to HTN without CAD group, the percentage of A
blood group was statistically higher and O blood group was significantly lower in
HTN with CAD group. Moreover, percentage of the angiography-proven CAD was higher
in A blood group than that in non-A blood group (p < 0.05). After adjusting for
confounding factors, A blood group was independently associated with CAD (odds
ratio (OR): 1.422; 95% confidence interval (CI): 1.017-1.987; p = 0.039) and GS
(beta = 0.055, p = 0.046) in patients with poor BP control. CONCLUSIONS: A blood
group was an independent risk factor for the presence and severity of CAD in
hypertensive patients with poor BP control.
PMID- 28513230
TI - Association of renin-angiotensin-aldosterone system gene polymorphisms with left
ventricular hypertrophy in patients with heart failure with preserved ejection
fraction: A case-control study.
AB - BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) has close ties
with hypertension, though risk factors to the development of HFpEF in
hypertensive patients are not fully understood. Left ventricular hypertrophy
(LVH) signifies the susceptibility toward diastolic heart dysfunction, and
genetic determinants of LVH as a result may serve as risk predictors for HFpEF in
hypertension. We investigated the role of three renin-angiotensin-aldosterone
system (RAAS) gene polymorphisms in the development of LVH in hypertensive
patients with a diagnosis of HFpEF. METHODS: A total of 176 hypertensive patients
with a diagnosis of HFpEF were divided to cases with LVH and controls without.
rs4343 and rs4291 of angiotensin-converting enzyme (ACE) and rs5186 of
angiotensin receptor type 1 were genotyped using PCR-RFLP method. RESULTS:
Genotypes and allele frequencies were significantly different between the case
and control groups for rs4343 and rs4291, whereas no difference was observed for
rs5186. CONCLUSION: Increased ACE activity explains the significant association
of rs4343 and rs4291 polymorphisms with LVH in the carriers. Furthermore,
findings support the pathophysiologic links between RAAS and increased LV mass in
hypertension and suggest a genetic susceptibility to HFpEF. Such polymorphisms
may serve as risk predictors of HFpEF in hypertensive patients.
PMID- 28513231
TI - Left atrial mechanical function and stiffness in patients with nondipper
hypertension: A speckle tracking study.
AB - BACKGROUND: Nondipper hypertension is associated with increased cardiovascular
morbidity and mortality. Speckle tracking echocardiography is a novel and
promising tool for detecting early changes in left atrial (LA) myocardial
dysfunction. Our aim was to evaluate the LA mechanical function and stiffness in
nondipper hypertensive patients by two-dimensional speckle tracking
echocardiography strain parameters. METHOD: This study included 80 hypertensive
patients. Hypertensive patients were divided into two groups: 50 dipper patients
(29 male, mean age 51.5 +/- 8 years) and 30 nondipper patients (17 male, mean age
50.6 +/- 5.4 years). LA volume indices, mitral annular velocities, and global
longitudinal LA strain were measured. The ratio of E/e' to LA strain was used as
an index of LA stiffness. RESULTS: Patients with nondipper hypertension showed
increased LA volume indices and decreased LA global strain (25.3 +/- 5.5 vs. 39.6
+/- 9.9%, P < 0.001). LA stiffness was increased in patients with nondipper than
in the dipper subjects (0.41 +/- 0.15 vs. 0.19 +/- 0.14, P < 0.001), and LA
strain and LA stiffness were related to LA volume indices. CONCLUSION: Patients
with nondipper hypertension have decreased LA global strain and increased
stiffness, in comparison with dipper group. LA stiffness and LA strain were
significantly related to LA volume indices. LA stiffness and LA strain can be
used for the assessment of LA function in patients with nondipper hypertension.
PMID- 28513232
TI - Right ventricular pressure elevated in one-kidney, one clip Goldblatt
hypertensive rats.
AB - Both renal and respiratory diseases are common with high mortality rate around
the world. This study was the first to compare effects of two kidneys, one clip
(2K1C) and one-kidney, one clip (1K1C) Goldblatt hypertension on right
ventricular pressure during normal condition and mechanical ventilation with
hypoxia gas. Male Sprague-Dawley rats were subjected to control, 2K1C, or 1K1C
groups. Twenty-eight days after the first surgery, animals were anesthetized, and
femoral artery and vein, and right ventricle cannulated. Systemic arterial
pressure and right ventricular systolic pressures (RVSP) were recorded during
ventilation the animals with normoxic or hypoxic gas. RVSP in the 1K1C group was
significantly more than the control and 2K1C groups during baseline conditions
and ventilation the animals with hypoxic gas. Administration of antioxidant
Trolox increased RVSP in the 1K1C and control groups compared with their
baselines. Furthermore, there was no alteration in RVSP during hypoxia in the
presence of Trolox. This study indicated that RVSP only increased after 28 days
induction of 1K1C but not 2K1C model. In addition, it seems that the response to
hypoxic gas and antioxidants in 1K1C is more than 2K1C. These data also suggest
that effects of 1K1C may partially be related to reactive oxygen species (ROS)
pathways.
PMID- 28513233
TI - Effect of statins on blood pressure: Analysis on adverse events released by FDA.
AB - OBJECTIVE: As a class of cholesterol-lowering drugs, statins have been reported
to cause unexpected decrease in blood pressure (BP). However, most studies in
this issue were subject to inadequate study design or very small sample size. The
present study was designed to examine the BP-lowering effect of various statins.
METHODS: Here we retrieved 5.9 million clinical reports submitted to FDA Adverse
Event Reporting System (FAERS) from 2004 to 2015. Meta-analysis was performed to
estimate the overall reporting odds ratio (ROR) of hypotension adverse events
concurrent with various statins (i.e., atorvastatin, simvastatin, and
rosuvastatin). RESULTS: Comparing the reporting rate of hypotension event between
statins and other drugs found that atorvastatin (pooled ROR = 1.26, adjusted p
value = 8.60 * 10-4) and simvastatin (pooled ROR = 1.94, adjusted p-value = 4.16
* 10-45) were significantly associated with reduction in BP. On the other hand,
the association between rosuvastatin and hypotension was observed to be
nonsignificant (adjusted p-value = 0.65). CONCLUSION: To our knowledge, this is
the first pooled analysis on large-scale data of adverse events to identify the
BP-lowering effect of statins. The results will contribute to the development of
novel statin-based antihypertensive therapies. In addition, the differential
effects of individual statins can warrant subsequent research on the underlying
mechanisms of BP control.
PMID- 28513234
TI - The development of the UK National Institute of Health and Care Excellence
evidence-based clinical guidelines on motor neurone disease.
AB - The care of people with motor neuron disease/amyotrophic lateral sclerosis is
often complex and involves a wide multidisciplinary team approach. The National
Institute for Health and Care Excellence (NICE) in the UK has produced an
evidence based guideline for the management of patients. This has made
recommendations, based on clear evidence or consensus discussion. The evidence is
often limited and areas for further research are suggested.
PMID- 28513235
TI - Impact of interaction between CYP1A1 genetic polymorphisms and smoking on
coronary artery disease in the Han of China.
AB - AIMS: To investigate the association of CYP1A1 genotype and additional gene
smoking interaction with coronary artery disease (CAD) risk based on a Chinese
case-control study. METHODS: A total of 1862 participants (1134 men, 728 women)
were selected, including 620 CAD patients and 1242 normal controls. Logistic
regression was performed to investigate association of CYP1A1 genotype, gene
gene, and gene-smoking interaction with CAD. Generalized multifactor
dimensionality reduction (GMDR) was used to screen the best gene-gene and gene
smoking interaction combination, cross-validation consistency, the testing
balanced accuracy, and the sign test, to assess if each selected interaction was
calculated. RESULTS: The carriers of homozygous mutant of rs4886605 polymorphism
and heterozygous of rs4646903 are associated with increased CAD risk than those
with wild-type homozygotes; OR (95% CI) was 1.98 (1.53-2.61) and 1.58 (1.24
1.96), respectively. The carriers of homozygous mutant of rs1048943 polymorphism
is associated with decreased CAD risk than those with wild-type homozygotes, OR
(95% CI) = 0.75 (0.60-0.93). GMDR model indicated a potential gene-gene
interaction between rs4886605 and rs4646903 and a potential gene-smoking
interaction between rs4886605 and smoking. Participants with rs4886605-CT or TT
and rs4646903-TC or CC genotype have the highest CAD risk, compared to
participants with rs4886605-CC and rs4646903-TT genotype; OR (95% CI) was 2.72
(2.03-3.61). In addition, we also found that smokers with rs4886605-CT or TT
genotype have the highest CAD risk, compared to nonsmokers with rs4886605-CC
genotype; OR (95% CI) was 3.07 (2.23-3.96). CONCLUSIONS: rs4886605 and rs4646903
are associated with increased CAD risk, but rs1048943 is associated with
decreased CAD risk; we also found gene-gene interaction between rs4886605 and
rs4646903 and gene-environment interaction between rs4886605 and smoking.
PMID- 28513236
TI - Enhanced gap junctional channel activity between vascular smooth muscle cells in
cerebral artery of spontaneously hypertensive rats.
AB - The aim of the present study is to investigate the effects of hypertension on the
gap junctions between vascular smooth muscle cells (VSMCs) in the cerebral
arteries (CAs) of spontaneously hypertensive rats (SHRs). The functions of gap
junctions in the CAs of VSMCs in SHRs and control normotensive Wistar-Kyoto (WKY)
rats were studied using whole-cell patch clamp recordings and pressure myography,
and the expression levels of connexins were analyzed using reverse transcription
quantitative polymerase chain reaction and Western blot analyses. Whole-cell
patch clamp measurements revealed that the membrane capacitance and conductance
of in situ VSMCs in the CAs were significantly greater in SHRs than in WKY rats,
suggesting that gap junction coupling is enhanced between VSMCs in the CAs of
SHRs. Application of the endothelium-independent vasoconstrictors KCl or
phenylephrine (PE) stimulated a greater vasoconstriction in the CAs of SHRs than
in those of WKY rats. The EC50 value of KCl was 24.9 mM (n = 14) and 36.9 mM
(n=12) for SHRs and WKY rats, respectively. The EC50 value of PE was 0.9 uM (n =
7) and 2.2 uM (n = 7) for SHRs and WKY rats, respectively. Gap junction
inhibitors 18beta-glycyrrhetinic acid (18beta-GA), niflumic acid (NFA), and 2
aminoethoxydiphenyl borate (2-APB) attenuated KCl-induced vasoconstriction in
SHRs and WKY rats. The mRNA and protein expression levels of the gap junction
protein connexin 45 (Cx45) were significantly higher in the CAs of SHRs than in
those of WKY rats. Phosphorylated Cx43 protein expression was significantly
higher in the CAs of SHRs than in those of WKY rats, despite the total Cx43 mRNA
and protein expression levels in the cerebral artery (CA) exhibiting no
significant difference between SHRs and WKY rats. Increases in the expression of
Cx45 and phosphorylation of Cx43 may promote gap junction communication among
VSMCs in the CAs of SHRs, which may enhance the contractile response of the CA to
vasoconstrictors.
PMID- 28513237
TI - T-cell subsets are associated with serum homocysteine concentration in patients
with essential hypertension.
AB - OBJECTIVE: To explore the association between serum homocysteine (Hcy)
concentration and T-cell subsets from patients with essential hypertension.
PATIENTS AND METHODS: A total of 218 essential hypertension patients were
recruited, of which 170 were H-type essential hypertensive and 48 were non-H-type
essential hypertensive. H-type essential hypertensive patients were divided into
three groups by concentration of serum Hcy. The peripheral blood T-cell subsets
(CD3+%, CD4+%, CD8+ T%, CD4+/CD8+) and clinical features including age, sex,
serum creatinine, uric acid, total cholesterol, triglycerides, low-density
lipoprotein cholesterol, and high-density lipoprotein cholesterol were recorded
and analyzed with T-cell subsets which were counted by fluorescence activated
cytometry. RESULTS: Compared with non-H-type hypertensive patients, CD4+ T-cell
percentage in peripheral blood was significantly decreased in H-type hypertensive
patients. Because of the increase of Hcy level, CD4+ T-cell percentage decreased.
Linear regression analysis showed that Hcy level was negatively correlated with
CD4+ T-cell percentage; however, it was positively correlated with CD3+ T-cell
percentage. CONCLUSION: A direct association between serum Hcy concentrations and
T-cell percentage was observed in patients with essential hypertension. This
observation indicates that T-cell subsets might play an important role in
hypertension.
PMID- 28513238
TI - Exercise and Dementia in Nursing Homes: Views of Staff and Family Carers.
AB - This paper reports the qualitative component of a randomized controlled trial
which evaluated the impact and feasibility of a physical exercise intervention on
individuals living with dementia in nursing homes. Interviews were conducted with
10 staff and nine family carers about their views and opinions of physical
exercise (n = 19). Thematic content analysis revealed both benefits and barriers
to physical exercise for individuals living with dementia in nursing homes.
Another theme was the influences of knowledge and understanding on individuals'
views of physical exercise. The involvement of staff and family carers in
research encourage their involvement in the implementation of research into
clinical practice. This can help to improve provisions of meaningful and
beneficial activities for individuals living with dementia in nursing homes. The
views and opinions of individuals living with dementia in nursing homes were not
considered, though it would be beneficial to include them in future research.
PMID- 28513239
TI - Multicenter evaluation of IV acyclovir use prior to, during, and after a national
shortage.
PMID- 28513240
TI - Prenatal diagnosis of monosomy 18p associated with holoprosencephaly: case
report.
PMID- 28513241
TI - Eric T MacKenzie, PhD (25 May 1950-2 March 2017).
PMID- 28513242
TI - Development of Physical Activity-Related Parenting Practices Scales for Urban
Chinese Parents of Preschoolers: Confirmatory Factor Analysis and Reliability.
AB - BACKGROUND: Valid instruments of parenting practices related to children's
physical activity (PA) are essential to understand how parents affect
preschoolers' PA. This study developed and validated a questionnaire of PA
related parenting practices for Chinese-speaking parents of preschoolers in Hong
Kong. METHODS: Parents (n = 394) completed a questionnaire developed using
findings from formative qualitative research and literature searches. Test-retest
reliability was determined on a subsample (n = 61). Factorial validity was
assessed using confirmatory factor analysis. Subscale internal consistency was
determined. RESULTS: The scale of parenting practices encouraging PA comprised 2
latent factors: Modeling, structure and participatory engagement in PA (23
items), and Provision of appropriate places for child's PA (4 items). The scale
of parenting practices discouraging PA scale encompassed 4 latent factors: Safety
concern/overprotection (6 items), Psychological/behavioral control (5 items),
Promoting inactivity (4 items), and Promoting screen time (2 items). Test-retest
reliabilities were moderate to excellent (0.58 to 0.82), and internal subscale
reliabilities were acceptable (0.63 to 0.89). CONCLUSION: We developed a theory
based questionnaire for assessing PA-related parenting practices among Chinese
speaking parents of Hong Kong preschoolers. While some items were context and
culture specific, many were similar to those previously found in other
populations, indicating a degree of construct generalizability across cultures.
PMID- 28513243
TI - Performance of Alpine Touring Boots When Used in Alpine Ski Bindings.
AB - Alpine touring (AT) equipment is designed for ascending mountains and snow skiing
down backcountry terrain. Skiers have been observed using AT boots in alpine (not
made for Alpine Touring) ski bindings. We tested the effect on the retention
release characteristics of AT boots used in alpine bindings. Ten AT ski boots and
5 alpine ski boots were tested in 8 models of alpine ski bindings using an ASTM
F504-05 (2012) apparatus. Thirty-one percent of the AT boots released
appropriately when used in alpine ski bindings. One alpine binding released
appropriately for all alpine and AT boots tested; 2 alpine ski bindings did not
release appropriately for any AT boots. Altering the visual indicator settings on
the bindings (that control the release torque of an alpine system) had little or
no effect on the release torque when using AT boots in alpine ski bindings. Many
combinations released appropriately in ski shop tests, but did not release
appropriately in the more complex loading cases that simulated forward and
backward falls; the simple tests performed by ski shops could produce a "false
negative" test result. These results indicate that using AT boots with alpine ski
bindings could increase the likelihood of lower leg injuries.
PMID- 28513244
TI - Different Relationship Between Physical Activity, Arterial Stiffness, and
Metabolic Status in Obese Subjects.
AB - BACKGROUND: Although the relationship between physical activity and arterial
stiffness has been shown in healthy persons, it remains controversial in obese
persons. METHODS: From January 2014 to September 2014, we evaluated 795 obese
subjects from 25 public health centers in Seoul, Korea. We compared physical
activity and brachial-ankle pulse wave velocity (baPWV) between obese subjects
with metabolic syndrome (MetS) (MO) and obese subjects without MetS (NMO).
RESULTS: The MO group had more men, higher body mass index (BMI), higher fasting
glucose level, lower high-density lipoprotein-cholesterol level, and higher
triglyceride level. The mean physical activity levels were similar between the 2
groups. baPWV was higher in the MO group than the NMO group. MO group showed
positive correlation between baPWV and physical activity (Ptrend = 0.04).
Interestingly, baPWV was significantly higher in the MO group than in the NMO
group in subjects with moderate and vigorous physical activity (1403.4 cm/sec vs
1349 cm/sec [95% CI 21.4 to 87.4], P < .05). Multivariate regression analysis
demonstrated that brachial-ankle pulse wave velocity was apparently associated
with age, BMI, blood pressure, and glucose level. CONCLUSIONS: In a community
based population, baPWV was higher in obese MetS group compared with obese non
MetS group. Physical activity showed different association with baPWV depending
on metabolic status.
PMID- 28513245
TI - Sit-Stand Desks To Reduce Workplace Sitting Time In Office Workers With Abdominal
Obesity: A Randomized Controlled Trial.
AB - BACKGROUND: Sit-stand desks reduce workplace sitting time among healthy office
workers; however, their metabolic and behavioral impact in higher risk
populations remains unknown. METHODS: 25 office workers with abdominal obesity
were randomized to an intervention (sit-stand workstation) or control group
(seated desk) for 12 weeks. Physical activity, sedentary behavior, and
cardiometabolic risk factors were assessed before and after the intervention
period in both groups. RESULTS: In comparison with the control group, which did
not change, the intervention group experienced significant reductions in workday
(344 +/- 107 to 186 +/- 101 min/day) and total (645 +/- 140 to 528 +/- 91
min/day) sitting time, as well as increases in workday standing time (154 +/- 108
to 301 +/- 101 min/day, P < .05). There were no changes in sitting or standing
time outside of work hours, steps taken each day, or any marker of
cardiometabolic risk in either group (all P > .05). CONCLUSION: Sit-stand desks
were effective in reducing workplace sedentary behavior in an at-risk population,
with no change in sedentary behavior or physical activity outside of work hours.
However, these changes were not sufficient to improve markers of cardiometabolic
risk in this population.
PMID- 28513247
TI - Use of nonbiologic treatments in antihistamine-refractory chronic urticaria: a
review of published evidence.
AB - BACKGROUND: Knowledge of effectiveness and safety of the nonbiologic,
nonantihistamine treatments used for chronic urticaria is important as in some
cases the principal guideline-recommended drug; omalizumab, has limited effect,
side effects or is too expensive or unavailable. Herein, we systematically review
the evidence for the use of the nonbiologic treatments in antihistamine
refractory chronic urticaria. METHODS: We performed a systematic review of the
literature using PubMed and Webofscience and identified studies that reported use
of one or more of the nonbiological, nonantihistamine treatment options for
chronic urticaria. The studies were evaluated based on study design, number of
patients, effect of treatment and safety. RESULTS: We identified 118 studies or
case series with 13 different treatments (azathioprine, chloroquine, colchicine,
cyclosporine, dapsone, intravenous immunoglobulin (IVIG), methotrexate,
montelukast, mycophenolate mofetil, plasmapheresis, sulfasalazine, tranexamic
acid and ultraviolet light (UV) A, UVB) totaling 1682 patients. There was a
paucity of controlled trials for most of the treatments reviewed albeit the
strongest evidence in favor of a beneficial effect in chronic urticaria was,
apart from montelukast and cyclosporine, seen for UV therapy and dapsone followed
by IVIG. CONCLUSION: The treatment options reviewed should be seen as potential
alternatives in treatment-resistant chronic urticaria where guideline-based
selections have failed. However, larger controlled trials are warranted to
advance the level of evidence, possibly supporting some treatments' future
recommendation in selected patients.
PMID- 28513248
TI - The Comparative Effects of Ankle Bracing on Functional Performance.
AB - Ankle sprains represent a common musculoskeletal injury that clinicians are
tasked with preventing and treating. Because of the prevalence of this injury,
ankle braces have been designed to prophylactically protect the joint and reduce
the incidence of repetitive sprains. Although an abundance of literature exists
focusing on the efficacy of braces in preventing ankle sprains in young, healthy,
and physically active populations, there is a scarcity of evidence specific to
the impact of these apparatuses on functional performance; therefore, the purpose
of this critically appraised topic (CAT) is to investigate the effects of ankle
braces on functional performance measures in such individuals. The outcomes of
this CAT will assist sport rehabilitation specialists with informed clinical
decision making in managing young, healthy, and physically active populations
using ankle braces. Do ankle braces hinder functional performance measures when
compared with an unbraced condition in a young, healthy, and physically active
population? A minimum of level II evidence research studies were surveyed for
this CAT. For this CAT, 1 randomized controlled trial and 3 prospective cohort
studies were selected. One study found a statistically significant main effect of
increased agility run times while participants wore ankle braces. Another study
demonstrated a statistically significant decrease in vertical jump height and
ankle range of motion while wearing braces. No other statistically significant
findings were reported among studies comparing unbraced with braced conditions.
Current data indicate that young, healthy, and physically active individuals may
experience varied performance effects when executing specific functional
performance tasks while wearing ankle braces. In general, bracing does not appear
to significantly impair performance on most functional tasks; however, decrements
were noted to increases in agility run time and decreases in vertical jump
height. Subsequent analysis indicated that a brace may result in decreased ankle
plantarflexion, dorsiflexion, eversion, and inversion range of motion, which may
underpin noted performance deficits.
PMID- 28513246
TI - Molecular composition and distribution of gap junctions in the sensory epithelium
of the human cochlea-a super-resolution structured illumination microscopy (SR
SIM) study.
AB - BACKGROUND: Mutations in the GJB2 gene, which encodes the Connexin26 (Cx26)
protein, are the most common cause of childhood hearing loss in American and
European populations. The cochlea contains a gap junction (GJ) network in the
sensory epithelium and two connective tissue networks in the lateral wall and
spiral limbus. The syncytia contain the GJ proteins beta 2 (GJB2/Cx26) and beta 6
(GJB6/Cx30). Our knowledge of their expression in humans is insufficient due to
the limited availability of tissue. Here, we sought to establish the molecular
arrangement of GJs in the epithelial network of the human cochlea using
surgically obtained samples. METHODS: We analyzed Cx26 and Cx30 expression in GJ
networks in well-preserved adult human auditory sensory epithelium using
confocal, electron, and super-resolution structured illumination microscopy (SR
SIM). RESULTS: Cx30 plaques (<5 MUm) dominated, while Cx26 plaques were subtle
and appeared as 'mini-junctions' (2-300 nm). 3-D volume rendering of Z-stacks and
orthogonal projections from single optical sections suggested that the GJs are
homomeric/homotypic and consist of assemblies of identical GJs composed of either
Cx26 or Cx30. Occasionally, the two protein types were co-expressed, suggesting
functional cooperation. CONCLUSIONS: Establishing the molecular composition and
distribution of the GJ networks in the human cochlea may increase our
understanding of the pathophysiology of Cx-related hearing loss. This information
may also assist in developing future strategies to treat genetic hearing loss.
PMID- 28513249
TI - Medicaid Expansion Produces Long-Term Impact on Insurance Coverage Rates in
Community Health Centers.
AB - BACKGROUND: It is crucial to understand the impact of the Affordable Care Act
(ACA). This study assesses changes in insurance status of patients visiting
community health centers (CHCs) comparing states that expanded Medicaid to those
that did not. METHODS: Electronic health record data on 875,571 patients aged 19
to 64 years with >= 1 visit between 2012 and 2015 in 412 primary care CHCs in 9
expansion and 4 nonexpansion states. We assessed changes in rates of total,
uninsured, Medicaid-insured, and privately insured primary care and preventive
care visits; immunizations administered, and medications ordered. RESULTS: Rates
of uninsured visits decreased pre- to post-ACA, with greater drops in expansion (
57%) versus nonexpansion (-20%) states. Medicaid-insured visits increased 60% in
expansion states while remaining unchanged in nonexpansion states. Privately
insured visits were 2.7 times higher post-ACA in nonexpansion states with no
increase in expansion states. Comparing 2015 with 2014: Uninsured visit rates
continued to decrease in expansion (-28%) and nonexpansion states (-19%),
Medicaid-insured rates did not significantly increase, and privately insured
visits increased in nonexpansion states but did not change in expansion states.
CONCLUSIONS: Medicaid expansion and subsidies to purchase private coverage likely
increased the accessibility of health insurance for patients who had previously
not been able to access coverage.
PMID- 28513251
TI - Comparison of the effects of 665 nm low level diode Laser Hat versus and a
combination of 665 nm and 808nm low level diode Laser Scanner of hair growth in
androgenic alopecia.
AB - BACKGROUND: This study aimed to evaluate the effectiveness of a combined set of
low level diode laser scanner (665 nm and 808nm) on hair growth, and assessment
of safety and effectiveness of a new laser scanner on hair growth treatment
procedure in androgenic alopecia. METHODS: 90 patients (18 to 70 years) with
androgenic alopecia were randomized into three groups. The first group (n=30)
received 655 nm red light using laser hat, the second group (n=30) received 655
nm red laser plus 808 nm infrared laser using a laser scanner of hair growth
device (with the patent number: 77733) and the third group (n=30) received no
laser as the control group. RESULTS: Patients in laser scanner group had better
results and showed a higher increase in terminal hair density compared with laser
hat group (mean of 9.61 versus 9.16 per cm2). We found significant decrease in
terminal hair density from baseline in control group (mean -1.8 per cm2,
p<0.0001). CONCLUSION: Results showed a statistically significant improvement in
the laser scanner of the hair growth group compared with laser hat and the
control group. The study showed that treatment with new laser devise had a
promising result without any observable adverse effects.
PMID- 28513250
TI - Combined measurements of fractional exhaled nitric oxide and nasal nitric oxide
levels for assessing upper airway diseases in asthmatic patients.
AB - BACKGROUND: Despite the close linkage between rhinitis, chronic rhinosinusitis
(CRS) and asthma, relevant biomarkers of both upper and lower airway inflammation
are rare. METHODS: Patients with asthma (without upper airway disease [UAD; n =
24], with rhinitis [n = 25], CRS [n = 24], and nasal polyps [n = 2]), isolated
rhinitis (n = 13), isolated CRS (n = 13), and 10 healthy controls were
prospectively recruited. Fractional exhaled nitric oxide (NO) levels at 50 mL/s
(FeNO50), nasal NO levels, Lund-Macay-scores of sinus computed tomography and an
asthma control questionnaire (ACQ) were evaluated. RESULTS: Asthma was associated
with higher FeNO50 levels irrespective of the UAD category. FeNO50 levels were
higher in asthmatics with CRS (median: 54.0 ppb) than those with rhinitis (35.2
ppb, p = 0.02) and those without UAD (34.3 ppb, p = 0.002). Nasal NO levels were
higher in rhinitis patients than other UAD categories, irrespective of the asthma
concomitance. Nasal NO levels were higher in asthmatics with rhinitis (112.8 ppb)
than those without UAD (67.2 ppb, p = 0.001) and those with CRS (57.6 ppb, p <
0.0001). A receiver-operating-characteristic curve analysis for detecting
comorbid allergic rhinitis (AR) in asthmatics showed a high area under the curve
(0.87). Nasal NO levels were positively correlated with FeNO50 levels (rho =
0.56, p = 0.003) in asthmatics with rhinitis. In contrast, they were negatively
correlated with the Lund-Macay (rho = -0.46, p = 0.03) and ACQ scores (rho =
0.52, p = 0.009) in asthmatics with CRS. CONCLUSIONS: Higher nasal NO levels
reflect the presence of AR, irrespective of asthma concomitance. Higher FeNO50
levels reflect the presence of CRS and asthma. These NO measurements are useful
for assessing comorbid UAD in asthmatics.
PMID- 28513252
TI - A novel model-based on FCM-LM algorithm for prediction of protein folding rate.
AB - The prediction of protein folding rates is of paramount importance in describing
the protein folding mechanism, which has broad applications in fields such as
enzyme engineering and protein engineering. Therefore, predicting protein folding
rates using the first-order of protein sequence, secondary structure and amino
acid properties has become a very active research topic in recent years. This
paper presents a new fuzzy cognitive map (FCM) model based on deep learning
neural networks which uses data obtained from biological experiments to predict
the protein folding rate. FCM extracts the important data features from the
protein sequence which then initializes the deep neural networks effectively. It
was found that the Levenberg-Marquardt (LM) algorithm for deep neural networks
can improve the prediction accuracy of the protein folding rates. The correlation
coefficient between the predicted values and those real values obtained from
experiments reached 0.94 and 0.9 in two independent numerical tests.
PMID- 28513253
TI - Synthesizing large-scale species trees using the strict consensus approach.
AB - Supertree problems are a standard tool for synthesizing large-scale species trees
from a given collection of gene trees under some problem-specific objective.
Unfortunately, these problems are typically NP-hard, and often remain so when
their instances are restricted to rooted gene trees sampled from the same
species. While a class of restricted supertree problems has been effectively
addressed by the parameterized strict consensus approach, in practice, most gene
trees are unrooted and sampled from different species. Here, we overcome this
stringent limitation by describing efficient algorithms that are adopting the
strict consensus approach to also handle unrestricted supertree problems.
Finally, we demonstrate the performance of our algorithms in a comparative study
with classic supertree heuristics using simulated and empirical data sets.
PMID- 28513254
TI - Peripapillary sparing in RDH12-associated Leber congenital amaurosis.
AB - BACKGROUND: Peripapillary sparing is a characteristic that is traditionally
described as pathognomonic for Stargardt disease. MATERIALS AND METHODS: We
present a multimodal assessment of four Leber congenital amaurosis (LCA) cases
with congenital macular atrophy and severely attenuated electroretinogram
findings caused by bilallelic mutations in RDH12. RESULTS: Fundus
autofluorescence imaging revealed a general loss of retinal pigment epithelium
across the macula except for the peripapillary region in both eyes of all
patients. Spectral domain-optical coherence tomography confirmed relative
preservation in this area along with retinal thinning and excavation throughout
the rest of the macula. LCA was diagnosed based on clinical exam and retinal
imaging, and subsequently confirmed with genetic testing. CONCLUSIONS:
Peripapillary sparing is a novel phenotypic feature of RDH12-associated LCA.
PMID- 28513255
TI - Successful mechanical thrombectomy in a comatose patient with cerebral venous
sinus thrombosis: A case report.
AB - Cerebral venous sinus thrombosis is a rare cause of stroke, which is routinely
treated with systemic heparin. Unfavourable outcome is often seen in severe
cases. Therefore alternative treatment methods should be explored in these
patients. Due to the risk of haemorrhagic complications, treatment without
administration of thrombolytics is of particular interest. This report presents a
case of successful mechanical thrombectomy, without the use of thrombolytics, in
a comatose patient with cerebral venous sinus thrombosis.
PMID- 28513256
TI - Do current OELs for silica protect from obstructive lung impairment? A critical
review of epidemiological data.
AB - Inhalation of respirable crystalline silica (RCS) can lead to serious health
effects such as silicosis and lung cancer. There also seems to be a general
consensus to consider that RCS exposure is associated with obstructive lung
impairment or chronic obstructive pulmonary disease (COPD), a leading cause of
mortality, morbidity, and disability worldwide. It is, however, not clear whether
occupational exposure levels (OELs), generally set to prevent silicosis, also
protect workers from developing an obstructive impairment. This review aims at
clarifying the potential relationship between RCS exposure and obstructive lung
impairment as defined by spirometry. Eleven studies that reported both silica
exposure levels and spirometry results were identified. We systematically
extracted data pertaining to (a) the population studied, (b) level of exposure to
RCS and other pollutants, (c) spirometry procedure and interpretation, and (d)
methodology used to investigate the relationship between RCS exposure and
spirometry. These studies add supporting evidence in favor of a qualitative
association between occupational activities exposing to RCS and obstructive lung
dysfunction. However, no well-founded quantitative estimate can be drawn from
these investigations; the available relevant literature does not allow defining a
RCS exposure threshold associated with an increased risk of obstructive lung
dysfunction, as defined by spirometry, in workers without silicosis. Further
research is needed, but, as highlighted in this review, conducting
epidemiological studies with both valid exposure and outcome measurements is a
real challenge.
PMID- 28513257
TI - Factors Associated With Levels of Physical Activity in Chronic Kidney Disease
Patients Undergoing Hemodialysis: The Role of Dialysis Versus Nondialysis Day.
AB - BACKGROUND: Patients on hemodialysis (HD) report lower physical activity (PA)
levels. We analyzed factors associated with low levels of PA in patients with
chronic kidney disease (CKD) and compared PA on HD day and non-HD. METHODS: 79
patients wore an accelerometer and were classified according to time spent on
moderate-to-vigorous PA (MVPA). Demographic data, BMI, comorbidities, clinical
status, and health-related quality of life (HRQoL) were checked for association
with PA. In addition, PA level was compared between days of HD and non-HD.
RESULTS: Accelerometer compliance was 78.5% [33 men and 29 women (53.96 +/- 15.71
yrs) were included in analysis]. 35.5% of sample achieved >=150min/week on MVPA.
Lower MVPA was associated with older age (OR = 5.80, 95% CI = 1.11 to 30.19, P =
.04), and lower score of physical function HRQoL (OR = 4.33, 95% CI = 1.23 to
15.23, P = .02). In addition, patients spent 9.73% more time on sedentary
behavior, 38.9% less on light PA and 74.9% less on MVPA on HD day versus non-HD
day. CONCLUSION: Age and physical function HRQoL were the main factors associated
to lower PA levels. In addition, lower time spent on PA during HD day suggest
that strategies for increasing physical activity levels during HD day such
exercising during HD session could help CKD patients to reach current PA
recommendations.
PMID- 28513258
TI - A Note from the Outgoing Editor.
PMID- 28513260
TI - Standing on the Shoulders of Nutrition's Giants: A Third Editor Assumes the Food
and Nutrition Bulletin.
PMID- 28513259
TI - Short Stature Is Associated With Overweight but Not With High Energy Intake in
Low-Income Quilombola Women.
AB - BACKGROUND: Population exposed to chronic undernutrition in early life seems to
be more susceptible to obesity in adulthood due to the development of mechanisms
that improve the efficiency of energy use. Therefore, these individuals have
relatively reduced energy requirements (thrifty phenotype). OBJECTIVE: To
investigate, among women living on severe socioeconomic vulnerability, whether
short stature, a marker for undernutrition in early life, is associated with
excess body weight but not with a high energy intake. METHODS: This cross
sectional study, carried out between July and November 2008, evaluated 1308 women
from all (N = 39) Quilombola communities of Alagoas. Adequacy of energy intake
was estimated by the ratio between energetic ingestion and the estimated energy
requirement (EER). RESULTS: The prevalence of short stature (<= 154.8 cm) was
43.0% and 52.4% had excess body weight (body mass index >= 25 kg/m2), being that
33.1% were overweight and 19.3% obese. Excess body weight was higher among women
with short stature (56.6% vs 49.2%; P = .008), even after adjusting for age,
energy intake, and per capita income (prevalence ratio = 1.16; 95% confidence
interval = 1.04; 1.28). The ratio of energy intake/EER was independent of women's
stature. CONCLUSION: Excess body weight among Quilombola women represents a
serious health problem. Short stature was significantly associated with excess
body weight but not with a high energy intake. "Thrifty phenotype" may be one of
the plausible explanations for this finding.
PMID- 28513261
TI - Rainer Gross Award Lecture 2016: A Laboratory in Your Pocket: Enabling Precision
Nutrition.
AB - The need for improving methods of nutritional assessment and delivering primary
health care globally cannot be overemphasized. While advances in medical
technology typically create more disparities because of access being limited to
resource-rich settings, a transition of health care to a mobile platform is
increasingly leveling the field. Technological advances offer opportunities to
scale laboratory procedures down to mobile devices, such as smartphones and
tablets. Globalization also provides the required infrastructure and network
capacity to support the use of mobile health devices in developing settings where
nutritional deficiencies are most prevalent. Here, we discuss some of the
applications and advantages provided by expanding markets of biomarker
measurement coupled with primary health care and public health systems and how
this is enhancing access and delivery of health services with significant global
impact.
PMID- 28513262
TI - Introduction to Rainer Gross.
PMID- 28513263
TI - Mortality Benefits of Vitamin A Are Not Affected by Varying Frequency, Total
Dose, or Duration of Supplementation.
AB - BACKGROUND: Although vitamin A supplementation reduces child mortality, it
remains unclear whether dosing frequency, total dose, or duration modifies
effectiveness. OBJECTIVE: Determine whether mortality effects of vitamin A vary
by dosing frequency, total dose, or duration. METHODS: Meta-analysis of
randomized controlled trials, identified by systematic review and expert opinion,
utilizing relatively standard World Health Organization doses in children <5
years. Meta-regression evaluated whether mortality effects varied by dosing
frequency, total dose, or supplementation duration. RESULTS: Identified 17
trials, including 1,180,718 children, mean (standard deviation [SD]) age 31.5
(15.4) months at baseline. Supplementation frequency ranged every 3 months-every
2 years, supplementation duration 4-60 months (mean = 15.4; SD = 12.8), and total
dose 134,361-2,200,000 IU (mean = 667,132 IU; SD = 540,795). Compared with
control, vitamin A reduced mortality 22% (95% confidence interval [CI] = 10-32; P
= 0.002). This protective effect was not modified by increasing supplementation
frequency (dose/year: relative risk [RR] = 1.02; 95% CI = 0.98-1.06; P = .22),
total dose (per 200,000 IU: RR = 1.02; 95% CI = 0.97-1.06; P = .31), nor
supplementation duration (per year: RR = 1.06; 95% CI = 0.97-1.15; P = 0.14).
Multivariate meta-regression showed similar results. Sensitivity analyses
excluding 1 controversial trial (Aswathi 2013) did not alter findings.
CONCLUSION: Results confirm benefits of vitamin A supplementation in children <5
years in nations with vitamin A deficiency, without influence of frequency, total
dose, or dosing duration within ranges evaluated. These findings inform design
and efficiency of vitamin A supplementation policies.
PMID- 28513265
TI - Perturbing Status of Vitamin B12 in Indian Infants and Their Mothers.
AB - BACKGROUND: Vitamin B12 deficiency in early life can adversely affect the growth
of developing brain with myriad of neurodevelopmental manifestations. At this
age, the deficiency is usually the result of low maternal levels. OBJECTIVES: To
assess the vitamin B12 status of healthy exclusively breast-fed Indian infants
aged 1 to 6 months and their mothers. METHODS: One hundred term exclusively
breast-fed infants aged 1 to 6 months attending pediatric outpatient department
were recruited. Hemogram, serum B12, folate, and ferritin levels were obtained
from each infant-mother pair. RESULTS: The prevalence of B12 deficiency in
infants was found to be 57%. Forty-six percent of mothers were deficient. There
was a positive correlation ( r = .23) between the B12 levels of the infants and
their mothers. CONCLUSION: There is a high prevalence of vitamin B12 deficiency
in Indian infants and their mothers. There is an urgent need to supplement our
population with vitamin B12, and the best time to do this would be antenatal.
PMID- 28513264
TI - Body Composition Analysis by Using Bioelectrical Impedance in a Young Healthy
Chinese Population: Methodological Considerations.
AB - OBJECTIVE: To develop a new bioelectrical impedance analysis (BIA) model for
analyzing body composition by using isotope dilution, magnetic resonance imaging
(MRI), and dual-energy X-ray absorptiometry (DEXA) as the reference methods in
young healthy Chinese populations. METHODS: Thirty healthy participants were
enrolled. Their body composition was analyzed using BIA and 3 reference methods.
We established a model that uniformed data from 3 references methods (isotope,
MRI, and DEXA) into 1 formula. This model was further validated with 209
participants. RESULTS: The following BIA body composition adjustment model was
developed: [Formula: see text], where X represents the impedance index; when K =
1, 2, and 3, Y represents total body water, fat mass, and bone mass,
respectively. The prediction accuracy of this formula was 93.3%. By incorporating
the data matrix, the protein mass was calculated using BIA: [Formula: see text].
In the verification part of this study, the lean body mass measured using DEXA
and BIA was 43.02 +/- 8.34 kg and 45.85 +/- 8.81 kg, respectively. Analysis
indicated that the model fit was extremely favorable ( R2 = .9997, P < .001).
CONCLUSIONS: The accuracy of BIA measurement on body composition and protein mass
is significantly improved by our work.
PMID- 28513266
TI - A Technical and Policy Case Study of Large-Scale Rescue and Redistribution of
Perishable Foods by the "Leket Israel" Food Bank.
AB - BACKGROUND: Food banks seeking to rescue and redistribute highly nutritious
perishable foods to simultaneously alleviate food insecurity and reduce food
waste often encounter practical, ethical, and political dilemmas. OBJECTIVES: We
present a case study of "Leket Israel," an Israeli food bank that uses an
effective large-scale logistical model for the rescue and redistribution of
perishable food and discuss the challenges and solutions it offers. RESULTS: The
organization operates in a rich country plagued with poverty and inequality,
where the government passively encourages nongovernmental organizations to
respond to the serious and growing problem of food insecurity. Operating under a
business-to-business model, Leket Israel distributes food via intermediary
nonprofit organizations (NPOs), enriching the food they provide with fresh
produce. Food is obtained through an Agricultural Gleaning project, Self-Growing
Farm project, and Meal Rescue project. The partnering NPOs then distribute the
food to people in need. Although the rescue and redistribution of highly
perishable food is more costly and complex than acquiring, storing, and
distributing dried and staple foods and it requires specialized knowledge and
infrastructure in order to maintain rigorous safety standards, it improves the
nutritional quality of the aid. In 2015, Leket Israel distributed 15 217 389 kg
of food, 90% of which was fruit and vegetables, to 180 partnering NPOs
nationwide, reaching an estimated 175 000 recipients. CONCLUSION: "Leket Israel"
offers a valuable model that can be studied and emulated by international
nutrition scientists, practitioners, and policy makers who are seeking to reduce
food insecurity and food waste in other countries.
PMID- 28513267
TI - Self-use of snake venom: The other side of the coin.
PMID- 28513268
TI - Effects of Volume Training on Strength and Endurance of Back Muscles: A
Randomized Controlled Trial.
AB - CONTEXT: Strength/resistance training volume has historically been supported in
the American College of Sports Medicine recommendations. However, for the back
muscles, exercise prescription related to the number of sets, such as single
versus multiple, is not well established in the literature. OBJECTIVE: The
purpose of this study was to compare the effects of 2 training volumes on
strength and endurance of back-extensor muscles in untrained young participants
with regard to a repeated-measures design. DESIGN: Randomized controlled trial.
SETTING: Laboratory of functional evaluation and human motor performance.
PARTICIPANTS: Forty-four untrained young participants (mean age = 21 y) were
randomized into single-set (n = 14), multiple-set (MSG, n = 15), and untrained
control (n = 15) groups. INTERVENTION: The single-set group and MSG underwent a
10-week progressive resistance training program (2 d/wk) using a 45 degrees
Roman chair. MAIN OUTCOME MEASURES: Back maximal strength (dynamometer) and
isometric and dynamic endurance (time limit, trunk extension-flexion cycles, and
electromyography muscle fatigue estimates). RESULTS: The results showed
differences between the MSG and control group for isometric endurance time (mean
= 19.8 s; 95% confidence interval, -44.1 to 4.8), but without time intervention
significance. Significant improvement after training (P < .05) was found
predominantly during dynamic endurance (number of repetitions) for both the MSG
(+61%) and single-set group (+26%) compared with preintervention, whereas the
control group reported no benefit. There was no significant (P > .05) difference
in either strength or electromyography estimates after training. CONCLUSIONS:
Both multiple and single volume training were efficient in promoting better back
endurance during dynamic performance based on mechanical variables (time and
number of repetitions).
PMID- 28513270
TI - Physiological and Performance Measures for Baseline Concussion Assessment.
AB - CONTEXT: Baseline testing is a common strategy for concussion assessment and
management. Research continues to evaluate novel measures for potential to
improve baseline testing methods. OBJECTIVES: The primary objective was to (1)
determine the feasibility of including physiological, neuromuscular, and mood
measures as part of baseline concussion testing protocol, (2) describe typical
values in a varsity athlete sample, and (3) estimate the influence of concussion
history on these baseline measures. DESIGN: Prospective observational study.
SETTING: Ryerson University Athletic Therapy Clinic. PARTICIPANTS: One hundred
varsity athletes. MAIN OUTCOME MEASURES: Frequency and domain measures of heart
rate variability, blood pressure, grip strength, profile of mood states-short
form, and the Sport Concussion Assessment Tool-2. RESULTS: Physiological,
neuromuscular performance, and mood measures were feasible at baseline.
Participants with a history of 2 or more previous concussions displayed
significantly higher diastolic blood pressure. Females reported higher total mood
disturbance compared with males. CONCLUSIONS: Physiological and neuromuscular
performance measures are safe and feasible as baseline concussion assessment
outcomes. History of concussion may have an influence on diastolic blood
pressure.
PMID- 28513271
TI - College Pitchers Demonstrate Directional Differences in Shoulder Joint Position
Sense Compared With Controls.
AB - CONTEXT: The relationship between overhead throwing and its effect on
proprioception is not well understood. It is important to gain a better
understanding of how these are related, to protect overhead athletes from an
increased risk of injury. OBJECTIVE: To investigate proprioceptive alterations in
the overhead thrower's shoulder. DESIGN: Cross-sectional study. Independent
variables are limb (dominant and nondominant), group (thrower or control), and
target angle. Dependent variables are joint position sense and range of motion.
SETTING: An orthopedic biomechanics lab and university athletic training
facility. PARTICIPANTS: Twelve Division I baseball pitchers and 13 nonthrowing
control subjects. INTERVENTION: Shoulder proprioception was assessed using an
active joint repositioning task administered with an iPod Touch. MAIN OUTCOME
MEASURE: Root mean square error and constant error of repositioning angles were
used to assess accuracy and directional patterns, respectively. RESULTS: Both
groups demonstrated significantly higher joint acuity at the 80 degrees external
rotation target angle compared with 60 degrees (1.5 degrees [0.5 degrees ], P =
.01). There were no differences in accuracy between groups. Constant error
revealed differing repositioning patterns between limbs for the pitchers and also
between groups for the dominant side. Although the throwing shoulder overshot the
target angles by 0.4 degrees , all nonthrowing shoulders undershot by an average
of 2.7 degrees . CONCLUSIONS: There is no difference in shoulder joint position
sense accuracy between throwers and nonthrowers, although both groups display
increased accuracy closer to their end range of external rotation. The throwing
shoulder demonstrates a different repositioning pattern, overshooting the desired
target angle, while all other shoulders undershoot.
PMID- 28513273
TI - The clinical value of Vav3 in peripheral blood for predicting lymphatic
metastasis of gastric cancer.
AB - BACKGROUND: Overexpression of Vav3, a gene involved in signal transduction,
promotes invasion and inhibits apoptosis in several cancers. The clinical value
of the protein product of this gene, Vav3, in the peripheral blood of gastric
cancer patients is unknown. We hypothesised increased serum Vav3 that related to
tissue levels and lymph node metastases. In addition, we further explored its
clinical value in respect of linked molecules Rac-1, MMP-7 and ICAM-1 Methods:
120 gastric cancer patients who had radical surgery were enrolled.
Immunohistochemistry was used to determine the expressions of Vav3, Rac-1, MMP-7
and ICAM-1 in gastric cancer mucosa and normal mucosa. ELISA was used to detect
these proteins in peripheral blood of gastric cancer patients and 100 age- and
sex-matched healthy controls. RESULTS: Vav3, Rac-1 and MMP-7 (P < 0.001), but not
ICAM-1 (P = 0.303) were more highly expressed by cancer tissues than normal
gastric mucosa. Serum levels of all molecules were higher than those in healthy
subjects (P < 0.001). Levels of Vav3, Rac-1 and MMP-7 decreased 2 weeks
postoperatively (all P < 0.001) but there was no change in ICAM-1 (P = 0.192).
Similarly, increased levels of Vav3, Rac-1 and MMP-7 were present in patients
with lymphatic metastasis than those without (all P < 0.001) but there was no
difference in ICAM-1 levels (P = 0.378). There were positive correlations between
Vav3 with Rac-1 and MMP-7 in cancer tissues (P < 0.001), and also between Vav3
and Rac-1 in pre-surgery blood (P = 0.003). CONCLUSIONS: Vav3 in peripheral blood
may serve as a biomarker for gastric cancer, and to predict the lymphatic
metastasis in gastric cancer.
PMID- 28513272
TI - Neuronal DNA Methyltransferases: Epigenetic Mediators between Synaptic Activity
and Gene Expression?
AB - DNMT3A and 3B are the main de novo DNA methyltransferases (DNMTs) in the brain
that introduce new methylation marks to non-methylated DNA in postmitotic
neurons. DNA methylation is a key epigenetic mark that is known to regulate
important cellular processes in neuronal development and brain plasticity.
Accumulating evidence disclosed rapid and dynamic changes in DNA methylation of
plasticity-relevant genes that are important for learning and memory formation.
To understand how DNMTs contribute to brain function and how they are regulated
by neuronal activity is a prerequisite for a deeper appreciation of activity
dependent gene expression in health and disease. This review discusses the
functional role of de novo methyltransferases and in particular DNMT3A1 in the
adult brain with special emphasis on synaptic plasticity, memory formation, and
brain disorders.
PMID- 28513275
TI - Relationship Between Lower-Extremity Strength and Subjective Function in
Individuals With Patellofemoral Pain.
AB - OBJECTIVE: Evaluate the relationship between subjective knee function and lower
extremity strength in individuals with patellofemoral pain (PFP). DESIGN: Cohort.
SETTING: Laboratory. PARTICIPANTS: Participants were 30 individuals with PFP (20
females and 10 males; 76.02 [17.88] kg, 173.04 [7.58] cm, and 24.9 [7] y). MAIN
OUTCOME MEASURES: Subjects completed the Activities of Daily Living Scale (ADLS)
and had lower-extremity hip and knee isometric strength assessed. Strength was
compared between low and high subjective functioning ADLS groups. Correlations
for strength and subjective function were assessed, with a linear regression
utilized to determine if strength predicted subjective function. RESULTS:
Quadriceps strength was significantly greater in the high subjective function
group (38.5 [13.9] percent body mass) than in the low subjective function group
(27.88 [8.96] percent body mass, P = .02). Significant correlations were seen
between the ADLS and all 5 lower-extremity strength measures (r = .376-.535).
Quadriceps strength was a strong predictor of subjective function in those with
PFP, explaining 28.6% of the total variance in the ADLS. CONCLUSIONS: Quadriceps
strength was a strong predictor of subjective function when assessed by the ADLS
in patients with PFP and significantly greater in those with higher subjective
function. A strong relationship exists between self-reported function and lower
extremity strength, suggesting the need to evaluate and treat lower-extremity
weakness.
PMID- 28513274
TI - Cognitive functioning and adjudicative competence: defendants referred for
neuropsychological evaluation in a psychiatric inpatient setting.
AB - OBJECTIVE: A paucity of peer-reviewed research exists regarding the relation
between cognitive functioning and adjudicative competence, despite increasing
awareness of cognitive deficits associated with serious mental illness. This
retrospective study sought to add to and expand upon existing research by
considering performance validity and court determinations of competence, when
available. METHOD: We compared demographic and cognitive variables of a group of
defendants with presumed valid testing admitted to an inpatient psychiatric
facility for evaluation of adjudicative competence and referred for
neuropsychological evaluation (n = 45) and compared individuals determined by the
evaluator and/or the court to be competent (n = 30) and incompetent (n = 15).
RESULTS: Defendants who were incompetent were more likely to be diagnosed with a
cognitive disorder, with a medium effect size. There was a difference in tests of
immediate and delayed memory as measured by the Repeatable Battery for the
Assessment of Neuropsychological Status (RBANS), with medium to large effects,
and high delayed memory scores were helpful in ruling out incompetence (Negative
predictive power = 85.71%). CONCLUSIONS: These results provide support for the
relationship between cognitive functioning and trial competence, particularly at
high and low levels of performance.
PMID- 28513276
TI - Attachment avoidance, but not anxiety, minimizes the joys of caregiving.
AB - Perhaps unlike other social roles that people may hold, caring for children
offers opportunities for both immense joy and incredible frustration. Yet what
predicts how parents will feel during caregiving experiences? In the current
study, we examined parents' (N = 152) positive emotion, negative emotion, and
felt meaning during caregiving using the Day Reconstruction Method. In addition,
we tested attachment anxiety and avoidance as predictors of parents' emotion
during caregiving relative to their other daily experiences. We found that
attachment avoidance was associated with elevated negative emotion and reduced
positive emotion and meaning in life across the entire day, whereas attachment
anxiety was associated with elevated negative emotion and marginally greater
meaning in life, but not positive emotion, across the entire day. Furthermore,
caregiving was associated with greater positive emotion and meaning, but not
negative emotion, compared to parents' other daily activities. Finally,
attachment avoidance, but not anxiety, was associated with lower levels of
positive emotion, negative emotion, and felt meaning during caregiving compared
to other daily activities. These findings are consistent with other evidence that
attachment avoidance is associated with deactivation of emotion in close
relationships and suggest that attachment avoidance minimizes the joys of
parenting.
PMID- 28513269
TI - Immune surveillance in melanoma: From immune attack to melanoma escape and even
counterattack.
AB - Pharmacologic inhibition of the cytotoxic T lymphocyte antigen 4 (CTLA4) and the
programmed death receptor-1 (PD1) has resulted in unprecedented durable responses
in metastatic melanoma. However, resistance to immunotherapy remains a major
challenge. Effective immune surveillance against melanoma requires 4 essential
steps: activation of the T lymphocytes, homing of the activated T lymphocytes to
the melanoma microenvironment, identification and episode of melanoma cells by
activated T lymphocytes, and the sensitivity of melanoma cells to apoptosis. At
each of these steps, there are multiple factors that may interfere with the
immune surveillance machinery, thus allowing melanoma cells to escape immune
attack and develop resistance to immunotherapy. We provide a comprehensive review
of the complex immune surveillance mechanisms at play in melanoma, and a detailed
discussion of how these mechanisms may allow for the development of intrinsic or
acquired resistance to immunotherapeutic modalities, and potential avenues for
overcoming this resistance.
PMID- 28513277
TI - Effect of Gastrocnemius Kinesio Taping on Countermovement Jump Performance and
Vertical Stiffness Following Muscle Fatigue.
AB - CONTEXT: Kinesio tape (KT) is a widely used intervention in the fields of sports
and rehabilitation. However, its effects on lower-extremity behavior during
functional activities are not entirely known. OBJECTIVE: To test the hypothesis
that application of KT can change performance and vertical stiffness (VS) during
the countermovement jump (CMJ) before and after a fatigue protocol. DESIGN: A
predesign and postdesign to study the effect of KT in 2 situations, prefatigue
and postfatigue. In each fatiguing condition, there were 2 conditions with and
without KT application on the gastrocnemius muscle. SETTING: Biomechanics
laboratory. PARTICIPANTS: Fifty healthy, nonathlete participants (26 females and
24 males). INTERVENTIONS: KT application on the gastrocnemius muscle and a
fatigue protocol to induce fatigue in plantar flexor muscles. MAIN OUTCOME
MEASURES: Various jumping parameters, including jump height, maximum force,
maximum power, rate of force development, eccentric lower-limb stiffness, and VS,
were calculated using the vertical ground reaction force data. Eccentric lower
limb stiffness and VS were calculated using a mass-spring model. The studied
variables can present lower-extremity elastic behavior and performance during
CMJ. RESULTS: The results of a 2-way repeated-measures analysis of variance
showed no significant effect for KT application. Fatigue resulted in lower values
of jump height, maximum power, and VS. Moreover, male subjects showed greater
values of jump height, maximum force, and maximum power than did females.
CONCLUSIONS: The main finding of this study was that gastrocnemius KT has no
effect on performance or elastic behavior of the lower-extremity during CMJ.
Moreover, KT cannot reduce the adverse effect of fatigue in a functional activity
such as CMJ. It seems that gastrocnemius KT is not effective for demanding
activities.
PMID- 28513278
TI - Infraspinatus Isolation During External Rotation Exercise at Varying Degrees of
Abduction.
AB - CONTEXT: External rotation (ER) strengthening exercises are a common component of
shoulder injury prevention and rehabilitation programs. They are primarily
intended to target the infraspinatus muscle, based on its role in glenohumeral
stabilization and inferior humeral glide. ER also recruits the posterior deltoid,
which can be undesirable due to its role in subacromial space narrowing.
OBJECTIVE: To determine the angle of humeral abduction that maximizes the
infraspinatus to posterior deltoid activation ratio (INFRA/PD) during ER. DESIGN:
Within-subjects repeated-measures controlled lab trial. PARTICIPANTS: A total of
10 healthy participants (5 males, 5 females) aged 21 (0.67) years participated in
the study. INTERVENTION: 7 consecutive repetitions of ER at 7 different abduction
angles ranging from 0 degrees to 90 degrees , with resistance normalized to 3%
body mass. MAIN OUTCOME MEASURES: Surface electromyography was performed on the
infraspinatus, middle deltoid, and posterior deltoid. Surface electromyography
data were processed to determine absolute muscle activation as well as INFRA/PD
at each abduction angle. Group means were compared between abduction angles using
1-way analysis of variance. RESULTS: Abduction significantly reduced overall
infraspinatus activity but increased posterior deltoid activity (P < .01).
Average and peak INFRA/PD decreased as the angle of abduction increased (P < .001
and P < .01, respectively). CONCLUSION: Our findings suggest that ER should be
performed in 0 degrees of abduction to maximize infraspinatus isolation. Slight
abduction, such as placing a towel under the humerus, as recommended by some
clinicians, may improve patient comfort, but did not increase infraspinatus
isolation in this study.
PMID- 28513280
TI - Application of Acoustic Radiation Force Impulse Elastography in Imaging of
Delayed Onset Muscle Soreness: A Comparative Analysis With 3T MRI.
AB - CONTEXT: Delayed onset muscle soreness is one of the most common reasons for
impaired muscle performance in sports and is associated with reduced muscle
strength and frequently observed both in professional and recreational athletes.
OBJECTIVE: To emphasize the diagnostic value of acoustic radiation force impulse
(ARFI) in imaging of delayed onset muscle soreness by comparing findings with
high-resolution 3T magnetic resonance imaging T2-weighted sequences. DESIGN: Case
series. SETTING: Laboratory environment. PARTICIPANTS: Fifteen healthy students
(7 females and 8 males; mean [SD]: age 24 [4] y, height 178 [10] cm, body weight
67 [12] kg). MAIN OUTCOME MEASURES: ARFI values, represented as shear wave
velocities of the gastrocnemius muscle and soleus muscle, as well as conventional
ultrasound, high-resolution 3T magnetic resonance imaging, creatine kinase
activity, extension range of the ankle joint, calf circumference, and muscle
soreness were assessed before (baseline) and 60 hours after (postintervention) a
standardized eccentric exercise. RESULTS: ARFI shear wave velocity values of the
gastrocnemius muscle revealed a statistically significant decrease of 19.1%
between baseline (2.2 [0.26] m/s) and postintervention (1.78 [0.24] m/s); P =
.01. At follow-up, the magnetic resonance imaging investigations showed
intramuscular edema for the gastrocnemius muscle in all participants
corresponding to a significant raise in T2 signal intensity (P = .001) and in T2
time values (P = .004). CONCLUSIONS: ARFI elastography seems to be an additional
sensitive diagnostic modality in the diagnostic workup of delayed onset muscle
soreness. Intramuscular shear wave velocities could represent an additional
imaging marker for the assessment and monitoring of ultrastructural muscle
injuries and therefore be helpful for individual training composition in elite
sports.
PMID- 28513281
TI - Short-Term Effects of Kinesio Taping on Muscle Recruitment Order During a
Vertical Jump: A Pilot Study.
AB - CONTEXT: Kinesio taping is commonly used in sports and rehabilitation settings
with the aim of prevention and treatment of musculoskeletal injuries. However,
limited evidence exists regarding the effects of 24 and 72 hours of kinesio
taping on trunk and lower limb neuromuscular and kinetic performance during a
vertical jump. OBJECTIVE: The purpose of this study was to analyze the short-term
effects of kinesio taping on height and ground reaction force during a vertical
jump, in addition to trunk and lower limb muscle latency and recruitment order.
DESIGN: Single-group pretest-posttest. SETTING: University laboratory.
PARTICIPANTS: Twelve male athletes from different sports (track and field,
basketball, and soccer). INTERVENTIONS: They completed a single squat and
countermovement jump at basal time (no kinesio taping), 24, and 72 hours of
kinesio taping application on the gluteus maximus, biceps femoris, rectus
femoris, gastrocnemius medialis, and longissimus. MAIN OUTCOME MEASURES: Muscle
onset latencies were assessed by electromyography during a squat and
countermovement jump, in addition to measurements of the jump height and
normalized ground reaction force. RESULTS: The kinesio taping had no effect after
24 hours on either the countermovement or squat jump. However, at 72 hours, the
kinesio taping increased the jump height (P = .02; d = 0.36) and normalized
ground reaction force (P = .001; d = 0.45) during the countermovement jump. In
addition, 72-hour kinesio taping reduced longissimus onset latency (P = .03; d =
1.34) and improved muscle recruitment order during a countermovement jump.
CONCLUSIONS: These findings suggest that kinesio taping may improve neuromuscular
and kinetic performance during a countermovement jump only after 72 hours of
application on healthy and uninjured male athletes. However, no changes were
observed on a squat jump. Future studies should incorporate a control group to
verify kinesio taping's effects and its influence on injured athletes.
PMID- 28513279
TI - w09, a novel autophagy enhancer, induces autophagy-dependent cell apoptosis via
activation of the EGFR-mediated RAS-RAF1-MAP2K-MAPK1/3 pathway.
AB - The EGFR (epidermal growth factor receptor) signaling pathway is frequently
deregulated in many malignancies. Therefore, targeting the EGFR pathway is
regarded as a promising strategy for anticancer drug discovery. Herein, we
identified a 2-amino-nicotinonitrile compound (w09) as a novel autophagy
enhancer, which potently induced macroautophagy/autophagy and consequent
apoptosis in gastric cancer cells. Mechanistic studies revealed that EGFR
mediated activation of the RAS-RAF1-MAP2K-MAPK1/3 signaling pathway played a
critical role in w09-induced autophagy and apoptosis of gastric cancer cells.
Inhibition of the MAPK1/3 pathway with U0126 or blockade of autophagy by specific
chemical inhibitors markedly attenuated the effect of w09-mediated growth
inhibition and caspase-dependent apoptosis. Furthermore, these conclusions were
supported by knockdown of ATG5 or knockout of ATG5 and/or ATG7. Notably, w09
increased the expression of SQSTM1 by transcription, and knockout of SQSTM1 or
deleting the LC3-interaction region domain of SQSTM1, significantly inhibited w09
induced PARP1 cleavage, suggesting the central role played by SQSTM1 in w09
induced apoptosis. In addition, in vivo administration of w09 effectively
inhibited tumor growth of SGC-7901 xenografts. Hence, our findings not only
suggested that activation of the EGFR-RAS-RAF1-MAP2K-MAPK1/3 signaling pathway
may play a critical role in w09-induced autophagy and apoptosis, but also imply
that induction of autophagic cancer cell death through activation of the EGFR
pathway may be a potential therapeutic strategy for EGFR-disregulated gastric
tumors.
PMID- 28513282
TI - Zanthoxylum alkylamides activate phosphorylated AMPK and ameliorate glycolipid
metabolism in the streptozotocin-induced diabetic rats.
AB - This study aimed to evaluate the effects of Zanthoxylum alkylamides on the
glycolipid metabolism of rats with streptozotocin (STZ)-induced diabetes.
Diabetic rats were given daily oral treatments of 2, 4, or 8 mg/kg bw alkylamides
for 28 days. Alkylamides significantly decreased fasting blood glucose and
fructosamine content, as well as relieved organ enlargement caused by diabetes.
The serum and liver triglyceride, malondialdehyde, and free fatty-acid contents
of rats with STZ-induced diabetes were significantly reduced. Total cholesterol
in the liver also significantly decreased. Quantitative polymerase chain reaction
(Q-PCR) and Western blot detected insignificantly increased (P > 0.05) mRNA
expression levels of adenosine monophosphate-activated protein kinase (AMPK) in
the skeletal muscle of diabetic rats. However, AMPK and p-AMPK (Thr172) protein
expression levels significantly increased. The mRNA and protein expression levels
of silencing information regulator 1 significantly increased. The mRNA expression
levels of acetyl-CoA-carboxylase (ACC) and protein p-ACC (Ser79) also increased.
The mRNA and protein expression levels of glucose transporter type 4 (GLUT4) were
significantly upregulated in the skeletal muscle cell membranes of diabetic rats.
Results indicated that alkylamides activated the AMPK-signaling pathway. Thus,
inhibiting ACC activity reduced fatty-acid synthesis. The rapid translocation of
GLUT4 mediated increased glucose transport rate and reduced blood glucose.
Therefore, alkylamides can ameliorate glucose and lipid metabolism disorders in
diabetic rats by activating the AMPK pathway.
PMID- 28513284
TI - Best Practices for Population Genetic Analyses.
AB - Population genetic analysis is a powerful tool to understand how pathogens emerge
and adapt. However, determining the genetic structure of populations requires
complex knowledge on a range of subtle skills that are often not explicitly
stated in book chapters or review articles on population genetics. What is a good
sampling strategy? How many isolates should I sample? How do I include positive
and negative controls in my molecular assays? What marker system should I use?
This review will attempt to address many of these practical questions that are
often not readily answered from reading books or reviews on the topic, but emerge
from discussions with colleagues and from practical experience. A further
complication for microbial or pathogen populations is the frequent observation of
clonality or partial clonality. Clonality invariably makes analyses of population
data difficult because many assumptions underlying the theory from which analysis
methods were derived are often violated. This review provides practical guidance
on how to navigate through the complex web of data analyses of pathogens that may
violate typical population genetics assumptions. We also provide resources and
examples for analysis in the R programming environment.
PMID- 28513283
TI - Molecular Characterization of Australian Isolates of Puccinia graminis f. sp.
tritici Supports Long-Term Clonality but also Reveals Cryptic Genetic Variation.
AB - Long-term surveys of pathogenicity in Puccinia graminis f. sp. tritici in
Australia have implicated mutation as a major source of virulence, at times
leading to the demise of stem-rust-resistant wheat cultivars and substantial
yield losses. Since 1925, these surveys have identified at least four occasions
on which exotic isolates of P. graminis f. sp. tritici appeared in Australia,
with each acting as a founding isolate that gave rise sequentially to derivative
pathotypes via presumed single-step mutation. The current study examined the
relationship between virulence and molecular patterns using simple-sequence
repeat (SSR) markers on selected isolates of P. graminis f. sp. tritici collected
in Australia during a 52-year period in order to propose an evolutionary pathway
involving these isolates. Studies of SSR variability among this collection of
isolates within a putative clonal lineage based on pathotype 21-0, first detected
in 1954 (the "21/34 lineage"), provided compelling evidence of clonality over the
52-year period, coupled with single-step acquisition of virulence for resistance
genes. It also supported the postulation that two triticale-attacking pathotypes
(34-2,12 and 34-2,12,13) detected in the early 1980s were derived from pathotype
21-0 via stepwise sequential acquisition of virulence for Sr5, Sr11, Sr27, and
then SrSatu. Some of the isolates examined that were regarded as members of the
race 21/34 lineage based on pathogenicity differed significantly in their SSR
genotypes, indicating that they may have originated from processes more complex
than simple mutation. This included two isolates of pathotype 21-0, which were
collected in 1994 and 2006. Given that sexual recombination in P. graminis is
rare or absent in Australia, the cryptic complexity observed could indicate that
one or more of these isolates arose as a consequence of asexual recombination.
PMID- 28513286
TI - Azelnidipine is a useful medication for the treatment of heart failure preserved
ejection fraction.
AB - BACKGROUND: The optimal therapy in patients with heart failure preserved ejection
fraction (HFpEF) and hypertension (HT) has not been revealed. The beta blocker
(BB) and the renin angiotensin aldosterone system inhibitor (RAAS-I) are
recommend as class IIa in patients with HFpEF. The calcium channel blocker (CCB),
a major anti-hypertensive drugs in Japan, is also recommend as class IIa in
patients with HFpEF. However, the difference between azelnidipine, an L type CCB,
and cilnidipine, an N type CCB, is unclear. We investigated the difference
between azelnidipine and cilnidipine in patients with HFpEF and HT. METHODS:
Twenty-five consecutive HFpEF patients treated with BB and RAAS-I from April 2013
to March 2015 were enrolled. Initially, cilnidipine was used, and then switched
to azelnidipine. Age, gender, blood pressure (BP), heart rate (HR), blood tests,
echocardiography, and cardiac-scintigraphy (123I-metaiodobenzylguanidine: MIBG)
were measured before and after six months from azelnidipine administration.
RESULTS: There was no statistically significant difference in BP. B type
natriuretic peptides were significantly reduced (pre-state: 195.4 +/- 209.7 pg/ml
and post-state: 140.7 +/- 136.4 pg/ml, p = 0.050). In echocardiography, the TEI
index tended to be decreased (pre-state: 0.47 +/- 0.15 and post-state: 0.42 +/-
0.08, p = 0.057). As for MIBG, there was no significant change in the
heart/mediastinum ratio. However, the washout rate was significantly reduced (pre
state: 44.7 +/- 12.2 and post-state: 40.7 +/- 12.1, p = 0.011). In addition,
there was no statistically significant change, although HR tended to decrease by
switching to azelnidipine (pre-state: 62.7 +/- 11.6 and post-state: 61.8 +/-
16.5, p = 0.373). CONCLUSIONS: In patients with HT and HFpEF, azelnidipine
improved the severity of HF and cardiac sympathetic nerve activity compared with
cilnidipine.
PMID- 28513285
TI - Hypertensive disorders of pregnancy increase the risk for chronic kidney disease:
A population-based retrospective study.
AB - Hypertensive disorders of pregnancy (HDP) and chronic kidney disease (CKD) are
well-known risk factors for cardiovascular disease (CVD) in later life. However,
few studies have investigated the association of HDP with CKD. Moreover, these
studies utilized either registry- or clinical-based data and did not include
subclinical CKD patients. To address this gap in the literature, we investigated
whether HDP is related to CKD, diagnosed based on the estimated glomerular
filtration rate (eGFR), in later life. We designed a population-based,
retrospective study, and reviewed the results of blood and physiological
examinations as well as the results of pregnancy data available in patients'
Maternity Health Record Books for 312 women. We identified 15 women with a
diagnosis of CKD based on the eGFR, and 14 women with HDP. We found that women
who experienced HDP had a high risk of CKD in later life compared with women
without HDP (odds ratio (OR): 4.854; 95% confidence interval (CI): 1.042-22.621).
Compared with normotensive women, those who were hypertensive at the time of the
examination were significantly associated with CKD (OR: 3.109; 95% CI: 1.213
11.510). Awareness regarding the risk for CKD and CVD in a relatively young age
can enable women to prevent diseases effectively.
PMID- 28513287
TI - Contact force technology integrated with 3D navigation system for atrial
fibrillation ablation: improving results?
AB - INTRODUCTION: Pulmonary veins isolation (PVI) by radiofrequency (RF) ablation is
currently an established treatment for symptomatic, drug-resistant paroxysmal
atrial fibrillation. Although the effectiveness of the therapy has been clearly
demonstrated, success rate after a single procedure is still sub-optimal. The
main reason for recurrences after PVI is electrical pulmonary vein-atrium
reconnection. In order to increase the likelihood of permanent PVI, the creation
of a transmural, durable lesion is mandatory. The main determinants of lesion
size and transmurality are power, stability, duration and contact-force during RF
application. In recent times, catheters with contact-force sensors have been
developed and released for clinical use. Areas covered: The present review
summarizes rational and clinical evidences for efficacy and safety of contact
force (CF) technology integrated into 3D navigation systems for AF ablation.
Expert commentary Although CF technology has a strong rational, clinical data on
the superior safety and efficacy of CF technology over traditional non-CF
catheters are still conflicting. The reason for that is very likely to rely on
the lack of definite data on how to optimize CF parameters and how to integrate
CF data with power, duration of RF applications and information on catheter
stability.
PMID- 28513288
TI - Growth arrest-specific protein 6 (Gas6) as a noninvasive biomarker for early
detection of diabetic nephropathy.
AB - BACKGROUND: To investigate the diagnostic level of cystatin C and growth arrest
specific gene 6 (Gas6) levels in elderly type 2 diabetic patients with different
degrees of diabetic nephropathy (DN). METHODS: Four hundred and eighty-two old
people, including 130 healthy controls, 130 normoalbuminuric diabetic patients,
122 with microalbuminuria, and 100 with macroalbuminuria, were recruited. Plasma
Gas6 and serum cystatin C levels were measured. RESULTS: Plasma Gas6
concentration was significantly lower in diabetic patients with microalbuminuria
or macroalbuminuria, as compared with diabetic subjects with normoalbuminuria;
while cystatin C was significantly higher. Gas6 was inversely correlated with
BMI, WHR, and HbA1c, while cystatin C was inversely correlated with urea nitrogen
and creatinine. Multivariate logistic regression analysis showed that, after
adjusted for established diabetes risk factors, higher plasma Gas6 was
significantly associated with a decreased risk of DN, while higher serum cystatin
C was significantly associated with an increased risk. Receiver operating
characteristic curve analysis showed that Gas6 was better than cystatin C as a
biomarker for early diagnosis and detection of DN, with a cutoff value of 9.435
ng/mL (86.1% sensitivity and 84.6% specificity). CONCLUSION: Compared to cystatin
C, Gas6 may be potentially a better noninvasive diagnostic biomarker for early
detection of DN.
PMID- 28513289
TI - Detection of meat species adulteration using high-resolution mass spectrometry
and a proteogenomics strategy.
AB - Due to the internationalisation of food production and distribution, there has
been a significant increase of food fraud in recent years. Food fraud can have
serious health implications, and it occurs when food manufacturers implement
unethical practices such as making false label claims as well as using additives
and fillers within their products to increase profitability. This has been a
serious concern. Meat adulteration was examined using a well-defined
proteogenomic annotation, carefully selected surrogate tryptic peptides and high
resolution mass spectrometry. Selected mammalian meat samples were homogenised
and the proteins extracted and digested with trypsin. Chromatography was achieved
using a 30-min linear gradient along with a BioBasic C8 100 * 1 mm column at a
flow rate of 75 ul min-1. The mass spectrometer was operated in full-scan high
resolution and accurate mass using resolving powers of 140,000 and 17,500 (FWHM)
in full-scan MS and MS/MS respectively. Data independent acquisition (DIA) mode
was used including 12 DIA MS/MS scans to cover the mass range 600-1200 m/z.
Methodically in silico analyses of myoglobin, myosin-1, myosin-2 and beta
haemoglobin sequences allow for the identification of a species-specific tryptic
peptide mass lists and theoretical MS/MS spectra. Following comprehensive MS,
MS/MS or DIA analyses, the method was capable of the detection and identification
of very specific tryptic peptides for all four targeted proteins for each animal
species tested with observed m/z below 3 ppm compared with the theoretical m/z.
The analyses were successfully performed with raw and cooked meat. Specifically,
the method was capable of detecting 1% (w/w) of pork or horse meat in a mixture
before and after cooking (71 degrees C internal temperature).
PMID- 28513290
TI - Examining the relationship between encouragement and health-related quality of
life among Muslims.
AB - This study examines the relationship between encouragement and health-related
quality of life (HRQOL) among a sample of American Muslims, in tandem with the
potential mediating effects of depression and spirituality. To conduct this cross
sectional study, a model was developed and tested using structural equation
modeling (SEM) with a community sample of Muslims (N = 284). The results indicate
that encouragement has a direct, positive effect on HRQOL. Neither depression nor
spirituality mediated the relationship between encouragement and HRQOL. Rather,
both variables exhibited a direct, independent effect on HRQOL. In addition,
spirituality exhibited an indirect effect on HRQOL through attenuating
depression. The findings underscore the importance of encouragement as a pathway
to enhance HRQOL among Muslims in post-9/11 America. The results also suggest
that spirituality can play a significant role in fostering HRQOL among Muslims,
both directly and indirectly by reducing the effects of depression on HRQOL.
PMID- 28513291
TI - Low-cost mobile air pollution monitoring in urban environments: a pilot study in
Lubbock, Texas.
AB - The complex nature of air pollution in urban areas prevents traditional
monitoring techniques from obtaining measurements representative of true human
exposure. The current study assessed the capability of low-cost mobile monitors
to acquire useful data in a city without a monitoring network in place (Lubbock,
Texas) using a bicycle platform. The monitoring campaign resulted in 30 days of
data along a 13.4 km fixed concentric route. Due to high sensitivities to
airflow, the apparent wind velocity was accounted for throughout the route. The
data were also normalized into percentiles in order to visualize spatial
patterns. The highest estimated pollution levels were located near frequently
busy intersections and roads; however, sensor issues resulted in lower
confidence. Additional research is needed concerning the appropriate use of low
cost metal oxide sensors for citizen science applications, as measurements can be
misleading if the user is unaware of sensors specifications. The simultaneous use
of several low-cost mobile platforms, rather than a single platform, as well as
the use of high-end cases, are recommended to create a more robust spatial
analysis. The issues addressed from this research are important to understand for
accurate and beneficial application of low-cost gaseous monitors for citizen
science.
PMID- 28513292
TI - Analysis of cutting-oil emulsion destabilization by aluminum sulfate.
AB - The destabilization mechanism of the high stable cutting-oil emulsion by aluminum
sulfate (Al2(SO4)3) was investigated since it can affect properties of aggregates
and following separation units. Al2(SO4)3 dosage and pH were key factors in the
destabilization. The effective separation occurred when precipitated Al(OH)3 is
dominated at the neutral pH of 6.5-7.0. The best separation can be achieved when
solid flocs were formed at 1.0 mM, which exceeded the dosage from the critical
coagulation concentration (CCC) of 0.75 mM. Two different mechanisms were proved
for the emulsion destabilization depending upon the Al3+ concentration under this
pH range. The first mechanism was the adsorption of Al(OH)3 on surface of oil
droplets, which led to the droplet coalescence. By increasing the Al3+ dosage,
the sweep flocculation by Al(OH)3 precipitates occurred. Al3+ dosage for
effective destabilization was increased in accordance with oil concentration. The
formation of aluminum hydroxide precipitates in bayerite structure was affirmed
by analyzing elemental composition and crystalline structure of flocs from the
destablization.
PMID- 28513293
TI - Effect of organic matter on mobilization of antimony from nanocrystalline
titanium dioxide.
AB - Antimony (Sb) is of increasing environmental concern worldwide. The sorption
behavior of Sb was investigated. Both Sb(III) and Sb(V) were likely to be sorbed
onto nanocrystalline titanium dioxide (TiO2). Sorption studies showed that the
Sb(V) sorption capacity and rate for TiO2 were greater than those of Sb(III). The
highest Sb(III) and Sb(V) sorption on TiO2, on the basis of the Langmuir
equation, were 333 and 588 mmol kg-1, respectively. The study suggested that TiO2
is an effective adsorbent for Sb removal. In addition, Sb mobilization in the
presence of humic acid (HA) was found to be highly pH-dependent. For pH values of
9-11, the addition of HA enhanced Sb mobilization significantly. The results
highlight the importance of organic matter in the mobilization of Sb in alkaline
contaminated environments.
PMID- 28513294
TI - Efficacy of propidium iodide and FUN-1 stains for assessing viability in
basidiospores of Rhizopogon roseolus.
AB - The use of spores in applications of ectomycorrhizal fungi requires information
regarding spore viability and germination, especially in genera such as
Rhizopogon with high rates of spore dormancy. The authors developed a protocol to
assess spore viability of Rhizopogon roseolus using four vital stains to quantify
spore viability and germination and to optimize storage procedures. They showed
that propidium iodide is an excellent stain for quantifying nonviable spores.
Observing red fluorescent intravacuolar structures following staining with 2
chloro-4-(2,3-dihydro-3-methyl-(benzo-1,3-thiazol-2-yl)-methylidene)-1
phenylquinolinium iodide (FUN-1) can help identify viable spores that are
activated. At 6 mo and 1 y, the spores kept in a water suspension survived better
than those left within intact, dry gasterocarps. Our work highlights the
importance of temperature, nutrients, and vitamins for maturation and germination
of spores of R. roseolus during 1 y of storage.
PMID- 28513296
TI - Confirmatory biopsy of men under active surveillance: extended versus saturation
versus multiparametric magnetic resonance imaging/transrectal ultrasound fusion
prostate biopsy.
AB - OBJECTIVE: The aim of this study was to evaluate the detection rate for
clinically significant prostate cancer (PCa) after multiparametric magnetic
resonance imaging (mpMRI)/transrectal ultrasound (TRUS) fusion biopsy versus
extended biopsy or saturation prostate biopsy (SPBx) in men enrolled on active
surveillance (AS). MATERIALS AND METHODS: From May 2013 to January 2016, 100 men
with very low-risk PCa were enrolled on AS. Eligible criteria were: life
expectancy greater than 10 years, cT1c, prostate-specific antigen (PSA) below 10
ng/ml, PSA density less than 0.20 ng/ml2, three or fewer unilateral positive
biopsy cores, Gleason score (GS) equal to 6 and greatest percentage of cancer in
a core 50% or lower. All patients underwent 3.0 T pelvic mpMRI before
confirmatory transperineal extended biopsy (20 cores) and SPBx (median 30 cores)
combined with mpMRI/TRUS fusion targeted biopsy (median four cores) of suspicious
lesions [Prostate Imaging Reporting and Data System (PI-RADS) 3-5]. Clinically
significant PCa was defined as the presence of at least one core with a GS of 4
or higher. RESULTS: After confirmatory biopsy, 16 out of 60 (26.6%) patients
showed significant PCa. Targeted biopsy of PI-RADS 4-5 versus PI-RADS 3-5 lesions
diagnosed six out of 16 (37.5%) and 12 out of 16 (87.5%) significant PCa,
respectively, with two false positives (5%). The detection rate for significant
PCa was equal to 68.8% on mpMRI/TRUS fusion biopsy, 75% on extended biopsy and
100% on SPBx. mpMRI/TRUS targeted biopsy and extended biopsy missed five out of
16 (31.2%) and four out of 16 (25%) PCa, respectively. CONCLUSIONS: Although
mpMRI may improve the diagnosis of significant PCa in men under AS, SPBx had a
higher detection rate for clinically significant PCa.
PMID- 28513298
TI - Cleaning of lead smelting flue gas scrubber sludge and recovery of lead, selenium
and mercury by the hydrometallurgical route.
AB - The expansion of the nonferrous metal smelting industry in the recent two decades
has resulted in the generation of massive quantities of flue gas scrubber sludge
containing hazardous heavy metals, such as cadmium, lead, arsenic, selenium and
mercury (Hg), posing a potential environmental threat. In this work, lead
smelting flue gas scrubber sludge was treated by a hydrometallurgical process to
achieve sludge cleaning and economic recovery of metal values lead, selenium and
mercury. The sludge was preliminarily leached by sodium chloride solution to
extract lead. Under the optimum conditions, 99.8% of lead was selectively leached
into the solution and subsequently precipitated by calcium oxide while almost the
entire selenium and mercury remained in residue. Ninety-eight percent of selenium
and 99.8% of mercury were further leached by hydrochloric acid solution with
sodium chlorate. 99.3% of mercury was precipitated as red mercuric oxide from the
Se-Hg leach liquor by adding sodium hydroxide. After the mercury was removed from
the solution, 97.5% of selenium was reduced and precipitated as crude selenium by
reduction with sodium sulfite. Recovery yields of lead, mercury and selenium by
this process were 99.6%, 98.9% and 95.5%, respectively.
PMID- 28513297
TI - Former food products safety: microbiological quality and computer vision
evaluation of packaging remnants contamination.
AB - The use of alternative feed ingredients in farm animal's diets can be an
interesting choice from several standpoints, including safety. In this respect,
this study investigated the safety features of selected former food products
(FFPs) intended for animal nutrition produced in the framework of the IZS PLV
06/14 RC project by an FFP processing plant. Six FFP samples, both mash and
pelleted, were analysed for the enumeration of total viable count (TVC) (ISO
4833), Enterobacteriaceae (ISO 21528-1), Escherichia coli (ISO 16649-1),
coagulase-positive Staphylococci (CPS) (ISO 6888), presumptive Bacillus cereus
and its spores (ISO 7932), sulphite-reducing Clostridia (ISO 7937), yeasts and
moulds (ISO 21527-1), and the presence in 25 g of Salmonella spp. (ISO 6579). On
the same samples, the presence of undesired ingredients, which can be identified
as remnants of packaging materials, was evaluated by two different methods:
stereomicroscopy according to published methods; and stereomicroscopy coupled
with a computer vision system (IRIS Visual Analyzer VA400). All FFPs analysed
were safe from a microbiological point of view. TVC was limited and Salmonella
was always absent. When remnants of packaging materials were considered, the
contamination level was below 0.08% (w/w). Of note, packaging remnants were found
mainly from the 1-mm sieve mesh fractions. Finally, the innovative computer
vision system demonstrated the possibility of rapid detection for the presence of
packaging remnants in FFPs when combined with a stereomicroscope. In conclusion,
the FFPs analysed in the present study can be considered safe, even though some
improvements in FFP processing in the feeding plant can be useful in further
reducing their microbial loads and impurity.
PMID- 28513299
TI - Anti-tumor effect of cisplatin in human oral squamous cell carcinoma was enhanced
by andrographolide via upregulation of phospho-p53 in vitro and in vivo.
AB - Oral squamous cell carcinoma is one of the most common neoplasm in the world.
Despite the improvements in diagnosis and treatment, the outcome is still poor
now. Thus, the development of novel therapeuticapproaches is needed. The aim of
this study is to assess the synergistic anti-tumor effect of andrographolide with
cisplatin (DDP) in oral squamous cell carcinoma CAL-27 cells in vitro and in
vivo. We performed Cell Counting Kit-8 proliferation assay, apoptosis assay, and
western blotting on CAL-27 cells treated with andrographolide, DDP or the
combination in vitro. In vivo, we also treated CAL-27 xenografts with
andrographolide or the combination, and performed terminal deoxynucleotidyl
transferase-mediated deoxyuridine triphosphate nick-end labeling assay and
immunohistochemical analysis of Ki-67. The results showed the combination of
andrographolide and DDP synergistically inhibited CAL-27 cell proliferation in
vitro and caused tumor regression in vivo in the CAL-27 xenografts. In addition,
the synergistic anti-tumor effect of andrographolide with synergistic was due to
an enhanced apoptosis. Moreover, the combination therapy upregulated the
expression level of p-p53 in vitro and decreased Ki-67 expression in vivo. Our
data indicate that the combination treatment of andrographolide and DDP results
in synergistic anti-tumor growth activity against oral squamous cell carcinoma
CAL-27 in vitro and in vivo. These results demonstrated that combination of
andrographolide with DDP was likely to represent a potential therapeutic strategy
for oral squamous cell carcinoma.
PMID- 28513301
TI - Modern strategies and capabilities for activation of the immune response against
tumor cells.
AB - Dendritic cells are professional antigen-presenting cells and the most potent
stimulators of various immune responses, such as antitumor responses. Modern
studies have not shown an effective antitumor immune response development in
patients with malignant tumors. The major cause is the decrease in functional
activity of dendritic cells in cancer patients through irregularities in the
maturation process to a functionally active form and in the antigen presentation
process to naive T lymphocytes. This review describes the main stages of cellular
antitumor immune response induction in vitro, aimed at resolving the problems
that are blocking the full functioning of dendritic cells, and additional
stimulation of antitumor immune response.
PMID- 28513300
TI - S100A11 regulates renal carcinoma cell proliferation, invasion, and migration via
the EGFR/Akt signaling pathway and E-cadherin.
AB - S100A11 is a S100 protein family member that contributes to cancer progression.
Upregulated in human renal cancer tissues, S100A11 may be a prognostic marker for
clear cell renal cell carcinoma, but how it functions in cancer is uncertain.
Thus, we studied S100A11 and noted knockdown of S100A11 using short hairpin RNA,
which inhibited proliferation, invasion, and migration of renal carcinoma cells
as well as increased expression of E-cadherin and decreased expression of
epidermal growth factor receptor/Akt in renal carcinoma cells. Therefore, S100A11
may be a key molecular target for treating renal carcinoma.
PMID- 28513302
TI - Controlled release of 1-methylcyclopropene from its functionalised electrospun
fibres under constant and linearly ramped humidity.
AB - The methodology to electrospin polystyrene (PS) fibres functionalised with the
inclusion complex between 1-methylcyclopropene (1-MCP) and alpha-cyclodextrin
(alpha-CD) has been developed successfully. Due to limited availability, alpha-CD
crystals instead of 1-MCP/alpha-CD complex were suspended in the electrospinning
(ES) solutions to investigate the ES process. The ES solutions were characterised
in terms of viscosity, conductivity and surface tension. Meanwhile, the fibres
were subjected to scanning electron microscopy. The average fibre diameter was
proportional to approximately one-sixth power of the capillary number of the ES
solution. Viscosity, which was a function of PS concentration and alpha-CD
loading, was the main property that dictated the spin ability of the ES
solutions. ES fibres with 1.5-4.4 MUm in diameter were produced with 12.5-20.0%
(w/w) PS in ES solution and an equal amount of the inclusion complex for PS. In
the case of the ES solutions of 20 wt% PS loaded with the inclusion complex from
0 to 100% (w/w) to PS, all the ES solutions were electrospinnable with the
average diameter ranging from 3.8 to 4.6 MUm. X-ray diffractometry indicated that
the alpha-CD crystals were homogeneously suspended on the fibre mats. Confocal
laser scanning microscopy showed that the crystals were suspended on the fibre
mats while being coated with a layer of PS. The complex-functionalised fibre was
formed from the ES solution of 20% PS and 50% (w/w) inclusion complex with the
ES. The release characteristics of 1-methylcyclopropene (1-MCP) from the
functionalised fibre and the inclusion complex were investigated real time under
linearly ramping humidity conditions at constant temperatures with a home-built
humidity regulating system coupled with gas chromatography. The irregular release
profiles were successfully modelled and the activation energies of release for
the functionalised fibre and inclusion complex were about 128 and 69 kJ/mol,
respectively..
PMID- 28513303
TI - Effects of Functional-Task Training on Older Adults With Alzheimer's Disease.
AB - The aim of this study was to verify the effects of functional-task training on
cognitive function, activities of daily living (ADL) performance, and functional
fitness in community-dwelling older adults with diagnosis of Alzheimer's disease
(AD). A total of 57 participants (22 functional-task training group [FTG], 21
social gathering group [SGG], 14 control group [CG]) were recruited. Participants
in both intervention groups carried out three 1-hr sessions per week of a
functional-task program and social gathering activities for 12 weeks. Significant
improvements were observed in executive functions (TMT, t-test, p = .03) in the
SGG and in upper limb strength (arm curl, t-test, p = .01) in the FTG. Functional
task training has no significant effect on cognitive function, ADL, and
functional fitness among people with AD, although it may contribute to slowing
down the process of deterioration this illness causes.
PMID- 28513304
TI - Using a sedimentation scanner to determine mangrove health responses to
sedimentation derived from dredging. An example from northwestern Australia.
AB - A sedimentation scanner was used to measure daily sediment height at 10 sites
associated with a 14 million cubic metre dredging project in Port Hedland
harbour, Western Australia, between July 2011 and May 2012. Data were collected
from seven potential impact sites, where up to 35 mm of additional sedimentation
was predicted via modelling to result from dredging and at three reference sites,
where background variation was monitored. A variety of mangrove habitat health
indices from each site (including leaf area and health, pneumatophore and faunal
burrow density) were collected before, during and after dredging. Despite
predictions, most impact sites received between 0 and 10 mm over the dredging
period, with one site experiencing a gain of 28 mm. Reference sites received
between 2 and 28 mm which was attributed to natural processes. It was concluded
that the health of Avicennia marina (Forssk.) Vierh. and Rhizophora stylosa
Griff., the most common mangroves, were neither affected by a net sedimentation
up to 28 mm of over a period of 11 months (i.e. 30.5 mm y-1) nor rapid changes
over shorter time periods such as 14 mm over two days. This technology could be
deployed in any tidally influenced sedimentary environment where short-term
processes were of interest.
PMID- 28513307
TI - Foundation for Veterinary Dentistry: Veterinary Dental Research Grant.
PMID- 28513311
TI - Scholarship Application.
PMID- 28513305
TI - Do Sitting, Standing, or Treadmill Desks Impact Psychobiological Indicators of
Work Productivity?
AB - BACKGROUND: This pilot study investigated the links between psychobiological
indicators of work productivity, prolonged desk sitting, and conditions whereby
office workers were able to interrupt sitting using a sit-stand or treadmill
desk. METHODS: Twenty participants visited our laboratory and completed their own
desk work in counterbalanced sit-only, sit-stand (Varidesk Pro Plus 48TM), and
sit-walk conditions (Infiniti TR1200-DTSTM). Steady-state visually evoked
potentials calculated from electroencephalography recordings during a set task at
the end of the workday assessed attentional resource. Salivary cortisol samples
were taken during the morning and afternoon to measure stress response. Within
subject analyses were used to compare work productivity indicators relative to
condition. RESULTS: No significant differences in mean steady-state visually
evoked potential amplitude were observed, although attentional resource
allocation was found to be the most effective following the sit-stand [1.01
(0.46) MUV] compared with the sit-walk [0.9 (0.28) MUV] and sit-only [0.91 (0.32)
MUV] conditions. The mean magnitude of decrease in cortisol was most apparent
when workers used treadmill (1.5 nmol/L; P = .007) and sit-stand (1.6 nmol/L; P =
.001) desks, and least evident in the sit-only condition (1.0 nmol/L; P = .146).
CONCLUSIONS: The findings highlight the potential benefits of standing or active
deskwork to the allocation of attentional resources and the regulation of stress.
PMID- 28513312
TI - Employment Opportunities.
PMID- 28513313
TI - Odontogenic Fibromyxoma in a Cat: First Confirmed Case in This Species.
AB - An inflammatory gingival mass surrounding resorbing teeth was diagnosed via
biopsy in a 9-year-old domestic shorthair cat. A dorsal rim excision was
performed to remove the entire mass with associated teeth and bone.
Histopathological diagnosis of the en bloc tissue revealed an odontogenic
fibromyxoma. Extensive literature review revealed few case reports of companion
animals with this neoplasm, and none in a feline patient. This report documents
the clinical presentation, diagnostic differentials, surgical therapy, and long
term follow-up of an odontogenic fibromyxoma in a cat.
PMID- 28513314
TI - Editorial.
PMID- 28513317
TI - Engagement in Physical Activity During Recess: Gender and Grade Level Differences
in the Elementary Grades.
AB - BACKGROUND: There are many purported benefits to recess including engaging in
physical activity, forming positive peer relationships, and taking a break from
the classroom. Current research, however, is inconclusive regarding the presence
of gender and developmental differences in physical activity that takes place
during recess. The purpose of this study was to examine differences in the amount
of physical activity that occurs during recess across gender and grade level.
METHODS: Students from first- and sixth-grade classrooms participated in the
study, and physical activity was measured using accelerometers to record the
number of steps taken during recess. RESULTS: A 2 * 2 factorial ANOVA indicated
sixth grade males engaged in more physical activity than sixth grade females,
first grade males, and first grade females. CONCLUSIONS: Because they are not
engaging in as much physical activity as their sixth grade male counterparts,
ways to help female and younger students take more steps during recess should be
explored.
PMID- 28513316
TI - Childhood Socioeconomic Disadvantage, Occupational, Leisure-Time, and Household
Physical Activity, and Diabetes in Adulthood.
AB - BACKGROUND: Regular physical activity is a key way to prevent disease. However,
we have a limited understanding of the socioeconomic precursors and
glucoregulatory sequelae of engaging in physical activity in different domains.
METHODS: We examined the associations among life course socioeconomic
disadvantage; meeting the physical activity guidelines with leisure-time physical
activity, occupational physical activity, or household physical activity; and
prediabetes and diabetes in the Midlife in the United States national study (N =
986). RESULTS: Childhood disadvantage was associated with lower odds of meeting
the guidelines with leisure-time physical activity (odds ratio = 0.75; 95%
confidence interval, 0.65-0.86). Adulthood disadvantage was associated with
higher odds of meeting the guidelines with occupational physical activity (odds
ratio = 1.94; 95% confidence interval, 1.49-2.53). Importantly, while meeting the
guidelines with leisure-time physical activity was associated with lower odds of
prediabetes and diabetes, we found no evidence for associations among
occupational physical activity, household physical activity, and glucoregulation.
CONCLUSION: Current US physical activity guidelines do not differentiate between
physical activity for leisure or work, assuming that physical activity in any
domain confers comparable health benefits. We documented important differences in
the associations among lifetime socioeconomic disadvantage, physical activity
domain, and diabetes, suggesting that physical activity domain potentially
belongs in the guidelines, similar to other characteristics of activity (eg,
type, intensity).
PMID- 28513318
TI - Neighborhood Built Environment and Socioeconomic Status in Relation to Active
Commuting to School in Children.
AB - BACKGROUND: The role of neighborhood type in active commuting to school (ACS) has
not been extensively studied in children. The purpose of this study was to
analyze the association between neighborhood built environment (walkability) and
neighborhood socioeconomic status (SES) with ACS among children. METHODS: A cross
sectional study of 310 Spanish children (aged 10-12 y; 51% male) was conducted in
2015. Walkability was defined as an index of 3 built environment characteristics
(ie, residential density, land-use mix, and street connectivity) based on
geographical information system data. Children's home and school neighborhoods
were evaluated. ACS was evaluated by questionnaire. Mixed model regression
analyses evaluated ACS in relation to neighborhood walkability and SES. RESULTS:
There were no significant SES-walkability interactions for ACS. Children living
in more walkable neighborhoods reported 2.5 more trips per week compared with
those living in less walkable neighborhoods (P < .001). Children attending
schools located in lower SES neighborhoods reported more ACS trips per week than
those attending schools in higher SES neighborhoods (P < .05). CONCLUSIONS: Home
neighborhood walkability and school-neighborhood SES were associated with ACS.
This study highlights the importance of assessing children's home environment and
school environment when ACS behavior is analyzed.
PMID- 28513319
TI - Effect of surface functionalizations of multi-walled carbon nanotubes on
neoplastic transformation potential in primary human lung epithelial cells.
AB - Functionalized multi-walled carbon nanotube (fMWCNT) development has been
intensified to improve their surface activity for numerous applications, and
potentially reduce toxic effects. Although MWCNT exposures are associated with
lung tumorigenesis in vivo, adverse responses associated with exposure to
different fMWCNTs in human lung epithelium are presently unknown. This study
hypothesized that different plasma-coating functional groups determine MWCNT
neoplastic transformation potential. Using our established model, human primary
small airway epithelial cells (pSAECs) were continuously exposed for 8 and 12
weeks at 0.06 MUg/cm2 to three-month aged as-prepared-(pMWCNT), carboxylated-(MW
COOH), and aminated-MWCNTs (MW-NHx). Ultrafine carbon black (UFCB) and
crocidolite asbestos (ASB) served as particle controls. fMWCNTs were
characterized during storage, and exposed cells were assessed for several
established cancer cell hallmarks. Characterization analyses conducted at 0 and 2
months of aging detected a loss of surface functional groups over time due to
atmospheric oxidation, with MW-NHx possessing less oxygen and greater lung
surfactant binding affinity. Following 8 weeks of exposure, all fMWCNT-exposed
cells exhibited significant increased proliferation compared to controls at 7 d
post-treatment, while UFCB- and ASB-exposed cells did not differ significantly
from controls. UFCB, pMWCNT, and MW-COOH exposure stimulated significant
transient invasion behavior. Conversely, aged MW-NHx-exposed cells displayed
moderate increases in soft agar colony formation and morphological transformation
potential, while UFCB cells showed a minimal effect compared to all other
treatments. In summary, surface properties of aged fMWCNTs can impact cell
transformation events in vitro following continuous, occupationally relevant
exposures.
PMID- 28513320
TI - CRISPR/Cas9-based Pten knock-out and Sleeping Beauty Transposon-mediated Nras
knock-in induces hepatocellular carcinoma and hepatic lipid accumulation in mice.
AB - Both Pten and Nras are downstream mediators of receptor tyrosine kinase
activation that plays important roles in controlling cell survival and
proliferation. Here, we investigated whether and how Pten loss cross-talks with
Nras activation in driving liver cancer development in mice. Somatic disruption
of hepatic Pten and overexpression of Nras were achieved in out-bred
immunocompetent CD-1 mice through a hydrodynamic delivery of plasmids carrying
Sleeping Beauty transposon-based integration of Nras and the CRISPR/Cas9-mediated
Pten knockout system. Concurrent Pten knockout and Nras knock-in induced
hepatocellular carcinoma, while individual gene manipulation failed. Tumor
development was associated with liver fibrosis, hyperlipidemia, hepatic
deposition of lipid droplets and glycogen, and hepatomegaly. At the molecular
level, lipid droplet formation was primarily contributed by upregulated
expression of genes responsible for lipogenesis and fatty acid sequestration,
such as Srebpf1, Acc, Pparg and its downstream targets. Our findings demonstrated
that Pten disruption was synergized by Nras overexpression in driving hepatocyte
malignant transformation, which correlated with extensive formation of lipid
droplets.
PMID- 28513322
TI - People with and without prosopagnosia have insight into their face recognition
ability.
PMID- 28513321
TI - Active Travel to and From School Among School-Age Children During 1997-2011 and
Associated Factors in China.
AB - BACKGROUND: Active travel to school (ATS) is positively associated with various
health indicators. The rapid social, economic, and environmental changes in China
provide a unique setting to study changes and predictors of ATS over time.
METHODS: Using logistic regression modeling, we analyzed data from the China
Health and Nutrition Survey during 1997 to 2011 (N = 9487, ages 6 to 17 years) to
estimate the change over time in ATS and to identify associated factors. RESULTS:
The prevalence of reported ATS among children dropped from 95.8% in 1997 to 69.3%
in 2011. ATS was common in children living closer to school, in middle school,
from low-income households, with low parental education status, and those without
a private vehicle. Children who were living in a metropolitan area and who had
more than 40 minutes of total PA per day were less likely to report ATS.
CONCLUSIONS: The decrease of ATS had been concurrent with the increase of the
children living at a longer distance from school and the increase of household
owning private vehicles which were associated with the rapid urbanization and
economic growth in China. Factors associated with the decreased ATS in China are
similar to other countries but the underlying reasons may be different.
PMID- 28513323
TI - Modulation of somatoparaphrenia following left-hemisphere damage.
AB - Somatoparaphrenic symptoms after left-hemisphere damage are rare. To verify the
potential role of body-related sensory (proprioceptive, visual, and
somatosensory) manipulation in patients experiencing sensations of hand
disownership, the symptoms of a patient suffering from right-hand
somatoparaphrenia were monitored and clinical and neuropsychological variables
were controlled. Four types of manipulation were administered: changes in spatial
position of the hand, multisensory stimulation, and self-observation using video
or mirrors. Multisensory visuo-tactile stimulation was efficacious in terms of
reducing somatoparaphrenia, and changes in the position of the hand produced some
positive effects. Third-person perspective self-observation did not, however,
result in any changes.
PMID- 28513324
TI - Biomechanical Comparison of Countermovement Jumps Performed on Land and in Water:
Age Effects.
AB - CONTEXT: The aquatic environment provides a low-impact alternative to land-based
exercise and rehabilitation in older adults. OBJECTIVE: Evaluate the biomechanics
of older adults and young adults performing jumping movements on land and in
water. DESIGN AND SETTING: Cross-sectional, mixed-factorial experiment;
adjustable-depth pool at sports medicine research facility. PARTICIPANTS: Fifty
six young adults (age = 22.0 [3.9] y) and 12 healthy older adults (age = 57.3
[4.4] y). INTERVENTIONS: Each participant performed 6 maximal effort
countermovement jumps: 3 jumps were performed on land, and 3 other jumps were
performed with participants immersed in chest-deep water. MAIN OUTCOME MEASURES:
Using data from the amortization and propulsive phases of jumping, the authors
computed the following kinetic and kinematic measures: peak and mean mechanical
power, peak force, amortization time and rate, unweighting and propulsive times,
and lower-extremity segment kinematics. RESULTS: Mechanical power outputs were
greater in younger adults (peak: 7322 [4035] W) versus older adults (peak:
5661.65 [2639.86] W) and for jumps performed in water (peak: 9387 [3981] W)
versus on land (peak: 4545.84 [1356.53] W). Peak dorsiflexion velocities were
greater for jumps performed in water (66 [34] deg/s) versus on land (4 [7]
deg/s). The amortization rate was 26% greater in water versus on land. The
amortization time was 20% longer in older adults versus young adults.
CONCLUSIONS: Countermovement jumps performed in water are mechanically specific
from those performed on land. Older adults jumped with longer unweighting times
and increased mechanical power in water. These results suggest that aquatic-based
exercise and rehabilitation programs that feature jumping movements may benefit
older adults.
PMID- 28513326
TI - The Effects of Blood Flow Restricted Electrostimulation on Strength and
Hypertrophy.
AB - CONTEXT: The combined effect of neuromuscular electrical stimulation (NMES) and
blood flow restriction (BFR) on muscle mass and strength has not been thoroughly
investigated. OBJECTIVE: To examine the effects of combined and independent BFR
and a low-intensity NMES on skeletal muscle adaptation. DESIGN: Exploratory
study. SETTING: Laboratory. PARTICIPANTS: Twenty recreationally active subjects.
MAIN OUTCOME MEASURES: Subjects had each leg randomly allocated to 1 of 4
possible intervention groups: (1) cyclic BFR alone, (2) NMES alone, (3) BFR +
NMES, or (4) control. Each leg was stimulated in its respective intervention
group for 32 minutes, 4 days per week for 6 weeks. Mean differences in size (in
grams) and isometric strength (in kilograms), between week 0 and week 6, were
calculated for each group. RESULTS: Leg strength increased 32 (19) kg in the BFR
+ NMES group, which differed from the 3 (11) kg change in the control group (P =
.03). The isolated NMES and BFR groups revealed increases of 16 (28) kg and 18
(17) kg, respectively, but these did not statistically differ from the control,
or one another. No alterations were statistically significant for leg size.
CONCLUSION: Compared with a control that received no treatment, the novel
combination of BFR and NMES led to increasing muscular strength of the knee
extensors, but not muscle mass which had a large interindividual variability in
response.
PMID- 28513325
TI - Developmental transitions in Arabidopsis are regulated by antisense RNAs
resulting from bidirectionally transcribed genes.
AB - Transcription terminators are DNA elements located at the 3' end of genes that
ensure efficient cleavage of nascent RNA generating the 3' end of mRNA, as well
as facilitating disengagement of elongating DNA-dependent RNA polymerase II.
Surprisingly, terminators are also a potent source of antisense transcription. We
have recently described an Arabidopsis antisense transcript originating from the
3' end of a master regulator of Arabidopsis thaliana seed dormancy DOG1. In this
review, we discuss the broader implications of our discovery in light of recent
developments in yeast and Arabidopsis. We show that, surprisingly, the key
features of terminators that give rise to antisense transcription are preserved
between Arabidopsis and yeast, suggesting a conserved mechanism. We also compare
our discovery to known antisense-based regulatory mechanisms, highlighting the
link between antisense-based gene expression regulation and major developmental
transitions in plants.
PMID- 28513327
TI - Dolphin Morbillivirus in a Fin Whale (Balaenoptera physalus) in Denmark, 2016.
AB - We studied the etiology of encephalitis in a fin whale (Balaenoptera physalus)
that stranded in 2016 on the coast of Denmark. Dolphin morbillivirus (DMV) was
detected in the brain and other organs. Phylogenetics showed close relation to
DMV isolated from a striped dolphin (Stenella coeruleoalba) from Spain in 2012.
PMID- 28513328
TI - TRYPANOSOMA CRUZI IN FREE-RANGING MAMMALIAN POPULATIONS IN SOUTH TEXAS, USA.
AB - Chagas disease, also known as American trypanosomiasis, is caused by the
flagellate protozoan Trypanosoma cruzi. It is a significant health concern in
South and Central America, where millions of people are infected or at risk of
infection, and is an emerging health concern in the US. The occurrence of Chagas
disease in natural environments is supported by mammal host species, but those
primary species may vary based on geographic location. In South Texas, the
primary host species for the disease is poorly understood, and required a field
study to determine the spatial distribution of T. cruzi prevalence in free
ranging mammals. Our study objectives were to determine the spatial distribution
and prevalence of T. cruzi parasites in free-ranging mammals. We compared T.
cruzi prevalence among species, among vegetative communities, and among different
topographies (i.e., floodplain versus upland). From December 2011 through
December 2013, 450 blood and tissue samples from geolocated free-ranging wildlife
mammal species were analyzed with the use of polymerase chain reaction to detect
protozoan T. cruzi DNA. We also calculated mammal abundance with the use of mark
recapture methodology and recorded capture-site characteristics such as
vegetation structure. We found that animals in grasslands had a significantly
lower infection rate when summed across all species compared with animals in
dense hardwoods and semi-improved woodlands (P=0.001). A higher percentage of
infections were found in the lower-elevation floodplain-65% (28/43) of animals
sampled, compared to upland areas-25% (9/36) of animals sampled. Our study
suggested that common free-ranging meso-mammals supported T. cruzi in natural
environments and are of public health concern in South Texas. Mitigation
strategies should consider a range of management activities to include vegetation
management, selective application of insecticides, and changes in human behavior
in high-risk areas.
PMID- 28513329
TI - Serologic Detection of Subtype-specific Antibodies to Influenza A Viruses in
Southern Sea Otters (Enhydra lutris nereis).
AB - There are approximately 3,000 southern sea otters (Enhydra lutris nereis) in the
nearshore environment along the California coast, US, and the species is
classified as Threatened under the Endangered Species Act. We tested sera from
661 necropsied southern sea otters sampled from 1997 to 2015 to determine overall
exposure to influenza A viruses (IAVs) and to identify subtype-specific antibody
responses. Using an enzyme-linked immunosorbent assay (ELISA), antibodies to IAV
nucleoproteins were detected in 160 (24.2%) otters, with seropositive animals
found in every year except 2008. When the ELISA-positive samples were tested by
virus microneutralization, antibody responses were detected to avian-origin
hemagglutinin subtypes H1, H3, H4, H5, H6, H7, H9, and H11. Strong antibody
responses to pandemic H1N1 (pdmH1N1) were also detected, indicating that
epizootic transmission of pdmH1N1 occurred among the southern sea otter
population after the emergence of this human-origin virus in 2009. We conclude
that southern sea otters are susceptible to infection with avian and human-origin
IAV and that exposure to a wide array of subtypes likely occurs during a given
otter's 10- to 15-yr life span. Important unanswered questions include what
effect, if any, IAV infection has on sea otter health, and how these animals
become infected in their nearshore environment.
PMID- 28513331
TI - Tracking cell proliferation using a nanotechnology-based approach.
AB - AIM: To develop an efficient nanotechnology fluorescence-based method to track
cell proliferation to avoid the limitations of current cell-labeling dyes.
MATERIAL & METHODS: Synthesis, PEGylation, bifunctionalization and labeling with
a fluorophore (Cy5) of 200 nm polystyrene nanoparticles (NPs) were performed.
These NPs were characterized and assessed for in vitro long-term monitoring of
cell proliferation. RESULTS: The optimization and validation of this method to
track long-term cell proliferation assays have been achieved with high
reproducibility, without cell cycle disruption. This method has been successfully
applied in several adherent and suspension cells including hard-to-transfect
cells and isolated human primary lymphocytes. CONCLUSION: A novel approach to
track efficiently cellular proliferation by flow cytometry using fluorescence
labeled NPs has been successfully developed. [Formula: see text].
PMID- 28513330
TI - THE PATHOGENESIS OF CLADE 2.3.4.4 H5 HIGHLY PATHOGENIC AVIAN INFLUENZA VIRUSES IN
RUDDY DUCK (OXYURA JAMAICENSIS) AND LESSER SCAUP (AYTHYA AFFINIS).
AB - Waterfowl are the natural hosts of avian influenza virus (AIV) and disseminate
the virus worldwide through migration. Historically, surveillance and research
efforts for AIV in waterfowl have focused on dabbling ducks. The role of diving
ducks in AIV ecology has not been well characterized. In this study, we examined
the relative susceptibility and pathogenicity of clade 2.3.4.4 H5 highly
pathogenic AIV (HPAIV) in two species of diving ducks. Juvenile and adult Ruddy
Duck (Oxyura jamaicensis) and juvenile Lesser Scaup (Aythya affinis) were
intranasally inoculated with A/Northern Pintail/WA/40964/2014 H5N2 HPAIV.
Additional groups of juvenile Lesser Scaups were inoculated with
A/Gyrfalcon/WA/41088/2014 H5N8 HPAIV. The approximate 50% bird infectious doses
(BID50) of the H5N2 isolate for adult Ruddy Ducks was <102 50% egg infectious
doses (EID50) and for the juvenile Lesser Scaups it was <104 EID50. There were
insufficient juvenile Ruddy Ducks to calculate the BID50. The BID50 for the
juvenile Lesser Scaups inoculated with the H5N8 isolate was 103 EID50. Clinical
disease was not observed in any group; however, mortality occurred in the
juvenile Ruddy Ducks inoculated with the H5N2 virus (three of five ducks), and
staining for AIV antigen was observed in numerous tissues from these ducks. One
adult Ruddy Duck also died and although it was infected with AIV (the duck was
positive for virus shedding and AIV antigen was detected in tissues), it was also
infected with coccidiosis. The proportion of ducks shedding virus was related to
the dose administered, but the titers were similar among dose groups. The group
with the fewest ducks shedding virus was the adult Ruddy Ducks. There was a trend
for the Lesser Scaups to shed higher titers of virus than the Ruddy Ducks. No
virus shedding was detected after 7 d postinoculation in any group. Similar to
dabbling ducks, Lesser Scaups and Ruddy Ducks are susceptible to infection with
this H5 HPAIV lineage, although they excrete lower titers of virus.
PMID- 28513332
TI - A fit-for-purpose method to monitor 16 European Union PAHs in food: results of
five years of official food control in two Italian regions.
AB - A gas-chromatographic single-quadrupole analytical method for the analysis of the
16 priority European Union (EU) polycyclic aromatic hydrocarbons (PAHs) in food
is presented. The method fulfils the request of Regulation EU 836/2011 for an
analytical procedure to be used for official control of PAHs in food in EU member
states. The sample preparation involves a pressurised liquid extraction (PLE)
with an in-cell clean-up step followed by a lipid removal using solid-phase
extraction (SPE) on a styrene divinylbenzene stationary phase (SDVB) and a final
gel-permeation chromatography (GPC) step. To reach a better sensitivity for all
the analytes, including the heaviest last eluting PAHs, 3 MUl of the purified
extract were injected in solvent vent mode using a programmable temperature
vaporization (PTV) injector. The isobaric PAH isomers were successfully separated
using an Agilent Technologies DB-17MS (20 m * 0.18 mm * 0.18 MUm) column. The
method was fully validated using an in-house approach and the sensitivity,
accuracy and precision obtained were satisfactory. The method expanded
uncertainty was estimated and it was verified that it was below the maximum
standard measurement uncertainty. Moreover, the results of 347 samples of meat
and meat products, fish and fish products and mussels collected from January 2012
to December 2016 in the Marche and Umbria regions of Italy are reported. None of
the samples exceed the maximum levels fixed by EU Regulation 835/2011, and clams
turned out to be the most contaminated among the food matrices analysed. Finally,
an estimate of the sum of four marker PAHs (benzo[a]anthracene,
benzo[b]fluoranthene, benzo[a]pyrene, chrysene) as indicator of the PAHs
contamination was done by comparison with the 16 carcinogenic PAHs sum.
PMID- 28513334
TI - Benefits of ion mobility for analysing monochloropropane-diol esters.
AB - This paper reports the first application and benefits of ion mobility in
combination with liquid chromatography and a transportable time-of-flight mass
spectrometer to the analysis of monochloropropane-diol esters (MCPDE) in
vegetable oils. The additional selectivity obtained with the ion mobility allowed
the quantitative analysis of MCPDEs as such in their intact form (direct
analysis) without any chemical derivatisation and, furthermore, without any
enrichment or purification step. This gain in selectivity manifests primarily in
the resolution of interferences originating, for example, from the diacylglycerol
components of palm oil. In silico calculations confirm that resolution of such
interferences would require mass resolutions higher than 200,000 at m/z 600,
e.g., in the case of signals of the 41K isotope of the PO DAG and the signals of
the sodiated PO MCPD. While such resolution can be obtained on certain state-of
the-art costly and laboratory-exhaustive research instruments, this study
demonstrates that even transportable time-of-flight MS can achieve the required
selectivity when combined with ion mobility. Further advantage of the described
approach is that the applied sample preparation is only dilution with minimum
consumable requirements and can be performed quickly even outside laboratories
directly in the field. The described results suggest that the application of ion
mobility in addition to LC-MS is likely to push the boundaries of contaminant
analysis especially for high-throughput screening investigations.
PMID- 28513333
TI - Atg9a deficiency causes axon-specific lesions including neuronal circuit
dysgenesis.
AB - Conditional knockout mice for Atg9a, specifically in brain tissue, were generated
to understand the roles of ATG9A in the neural tissue cells. The mice were born
normally, but half of them died within one wk, and none lived beyond 4 wk of age.
SQSTM1/p62 and NBR1, receptor proteins for selective autophagy, together with
ubiquitin, accumulated in Atg9a-deficient neurosoma at postnatal d 15 (P15),
indicating an inhibition of autophagy, whereas these proteins were significantly
decreased at P28, as evidenced by immunohistochemistry, electron microscopy and
western blot. Conversely, degenerative changes such as spongiosis of nerve fiber
tracts proceeded in axons and their terminals that were occupied with aberrant
membrane structures and amorphous materials at P28, although no clear-cut
degenerative change was detected in neuronal cell bodies. Different from
autophagy, diffusion tensor magnetic resonance imaging and histological
observations revealed Atg9a-deficiency-induced dysgenesis of the corpus callosum
and anterior commissure. As for the neurite extensions of primary cultured
neurons, the neurite outgrowth after 3 d culturing was significantly impaired in
primary neurons from atg9a-KO mouse brains, but not in those from atg7-KO and
atg16l1-KO brains. Moreover, this tendency was also confirmed in Atg9a-knockdown
neurons under an atg7-KO background, indicating the role of ATG9A in the
regulation of neurite outgrowth that is independent of autophagy. These results
suggest that Atg9a deficiency causes progressive degeneration in the axons and
their terminals, but not in neuronal cell bodies, where the degradations of
SQSTM1/p62 and NBR1 were insufficiently suppressed. Moreover, the deletion of
Atg9a impaired nerve fiber tract formation.
PMID- 28513335
TI - TiO2/UV-assisted rhodamine B degradation: putative pathway and identification of
intermediates by UPLC/MS.
AB - The present study was designed to evaluate the photocatalytic degradation of
Rhodamine B (Rh-B) in a self-assembled TiO2-assisted system under UV light
irradiation. Chemical oxygen demand, total organic carbon and high-performance
liquid chromatography analyses confirmed the elevated Rh-B degradation level. A
stepwise meticulous breakdown pathway based on the ultra-performance liquid
chromatography coupled with electrospray ionization mass spectrometry is
proposed. Results demonstrated that the degradation of Rh-B mainly occurred via N
de-ethylation process, and N-de-ethylated intermediate products were further
oxidized into acids and alcohols. Reduction in toxicity of the dye by the
formation of metabolites was measured using human cell lines (MTT assay) and
toxicity tests based on shrimp Artemia salina. Noticeably, the degraded
intermediates of Rh-B revealed low or non-toxicity than the original dye
molecule. Therefore, it can be inferred that the TiO2-assisted photocatalysis
could be beneficial for the degradation of recalcitrant compounds and textile
wastewater effluents, and for the elimination of toxicity therein.
PMID- 28513336
TI - Use of Tenax(r) films to demonstrate the migration of chemical contaminants from
cardboard into dry food.
AB - Contaminants in food packaging are a challenge of our time since the packaging
material itself has been found to represent a source of food contamination
through the migration of substances from it. Before first use, packaging
materials destined for the packaging of dry foods can be evaluated by performing
migration experiments with the simulant for dry foods, Tenax(r). This simulant is
commercially available as a powder that is more difficult to handle during the
migration experiments. This paper reports the development of a Tenax film. The
film can be applied to the cardboard surface to conduct the migration test. After
the migration is completed, the film can be easily extracted to determine the
concentration of the contaminants in the film. Finally, the performance of the
Tenax film was compared with the conventional Tenax powder for the evaluation of
15 model migrants.
PMID- 28513337
TI - Assessment of applicability index for better management of municipal solid waste:
a case study of Dhanbad, India.
AB - Selection of suitable municipal solid waste management (MSWM) options is one of
the major challenges in urban areas of the developing countries. Success of MSWM
requires accurate data of generation rate, composition and physico-chemical
characteristics of solid wastes. Improper handling of solid waste can have
significant environmental and aesthetical impacts. The present study proposes a
new method (applicability index - Pik values) for identifying the most
appropriate disposal option with the help of applicability values of Composting
CP, Incineration-IP and Landfill-LP for individual components of MSW based on the
results of the physico-chemical analysis of the collected representative solid
waste samples from the study area, Dhanbad, India. The mean values of moisture
content, carbon, hydrogen, oxygen, nitrogen, sulfur, volatile organic carbon,
fixed carbon, ash content, density and calorific values (CV) of individual
components were used as input values in this process. Based on the proposed
applicability index (Pik), the highest Pik values were obtained for incineration
(IP) for plastics, polythene, paper, coconut shell, wood, cardboard, textile,
thermocol (polystyrene), rubber, sugarcane bagasse, cow dung and leather wastes
(IP > CP > LP) due to high CV of these solid waste components; the highest Pik
values were obtained for composting (CP) of kitchen waste (CP > IP > LP); and the
highest Pik values for inert wastes were obtained for landfill option (LP > IP >
CP). The highest Pik value for a particular waste for a specific treatment option
signifies that the waste is suitable for treatment/disposal using that option.
PMID- 28513339
TI - Juggling thoughts and feelings: How do female patients with borderline
symptomology and substance use disorder experience change in mentalization-based
treatment?
AB - OBJECTIVE: The aim of this study was to explore the experience of central
psychological change processes for female patients with borderline symptomology
and substance use disorder in mentalization-based treatment. METHOD: Semi
structured qualitative interviews on experiences from mentalization-based
treatment with 13 participants were conducted. The interview material was
analysed within a hermeneutical-phenomenological epistemology, with emphasis on
researcher reflexivity. RESULTS: The following themes regarding central
psychological change processes were found: "by feeling the feeling," "by thinking
things through," "by walking in your shoes to see myself" and "by stepping
outside of own bad feelings in seeing you." Two of these themes dealt with intra
psychic modes of how to relate to own mind-states. First, they had a shift from
avoiding emotions into tolerating emotions. Second, they discovered the ability
to think mental states through. Two themes dealt with mental stances for dealing
with interpersonal situations, where one mode included a self-reflective stance
in difficult encounters, and the other mode entailed an empathic reflective
stance by exploring others' intentionality. CONCLUSIONS: The findings are in line
with theoretical assumptions that increasing mentalizing capacity is a central
change process for these patients. Furthermore, the findings demonstrate the
complex interaction between different modes of mentalizing.
PMID- 28513338
TI - Worldwide Surveillance, Policy, and Research on Physical Activity and Health: The
Global Observatory for Physical Activity.
AB - BACKGROUND: The Global Observatory for Physical Activity (GoPA!) was launched in
response to the physical inactivity pandemic. The aim of this article is to
present current information about surveillance, policy, and research on physical
activity (PA) and health worldwide. METHODS: Information was collected for 217
countries. For 139 of these nations we identified a contact who confirmed
information's accuracy and completeness. Associations were calculated among
surveillance, policy and research categories. RESULTS: Of the 139 countries,
90.6% reported having completed 1 or more PA survey, but less than one-third had
3 or more. 106 included PA on a national plan, but only one-quarter of these were
PA-specific. At least 1 peer reviewed publication was identified for 63.3% of the
countries. Positive associations (P < .001) were found between research and
policy (rho = 0.35), research and surveillance (rho = 0.41), and surveillance and
policy (rho = 0.31). Countries with a standalone plan were more likely to have
surveillance. Countries with more research were more likely to have a standalone
plan and surveillance. CONCLUSIONS: Surveillance, policy, and research indicators
were positively correlated, suggesting that action at multiple levels tends to
stimulate progress in other areas. Efforts to expand PA-related surveillance,
policy, and research in lower income countries are needed.
PMID- 28513341
TI - Adolescent Pregnancy and Increasing Body Mass Index: Risks and Benefits.
PMID- 28513340
TI - Questions About Cervical and Breast Cancer Screening Knowledge, Practice, and
Outcomes: A Review of Demographic and Health Surveys.
AB - United Nation's Sustainable Development Goals and the World Health Organization's
Global Monitoring Framework support a strong global commitment to reducing the
high burden of cervical and breast cancers among low- and middle-income
countries. Strategies include vaccination, screening, and early diagnosis.
Population-based surveys, such as those conducted by the Demographic and Health
Surveys (DHS) Program, can collect the information needed to guide cancer control
efforts in a standardized comparable manner. We identified and evaluated the
breadth of breast and cervical cancer screening information that was collected by
the DHS from 1984 through 2015. Then, we determined if these surveys currently
provide the specific and measurable data about both the quantity and quality of
cancer screening needed to guide national efforts to reduce the overall effects
of cervical and breast cancers. We searched the DHS website to identify surveys
conducted between the start of the DHS Program in 1984 and November 2015 that
included questions about breast and cervical cancer screening. The relevant
questions were extracted from the questionnaire, translated into English, and
grouped by themes. Of the 90 countries where DHS surveys have been implemented,
cervical cancer screening questions were included in 22 countries (24.4%) and
breast cancer screening questions in 18 countries (20.0%). The common themes
identified were disease knowledge, screening knowledge, screening practice, and
screening outcomes. Most countries with survey questionnaires available for
review addressed at least one aspect of screening practice (88.9% of cervical and
87.5% of breast), although few countries queried knowledge and outcomes.
Questions that assess varied aspects of breast and cervical cancer screening have
been incorporated into relatively few DHS surveys. The themes identified could
guide the design of a standard set of questions for use in future population
based surveys and enable evaluation beyond the existence of screening, which
would include assessment of the quality and impact of cervical and breast cancer
screening.
PMID- 28513342
TI - Integration in the Psychodynamic Psychotherapy of Severe Personality Disorders:
The Conversational Model.
AB - The psychotherapy of commonly occurring severe personality disorders-borderline,
narcissistic, avoidant, dependent, obsessive compulsive, and schizoid-presents
the therapist with a unique therapeutic challenge, as each personality disorder
rarely occurs alone. Integration of what is most useful and what works in each
model is being proposed to enable a more successful approach to the diversity of
presentations. We describe the conversational model, some outcome research, and
descriptive studies to illustrate this. Based in psychoanalytic theory, the
conversational model is integrated with trauma theory, findings in memory
research, linguistics, neurophysiological data, and, above all, on the
observations of clinical experiences. Our emphasis in this article is on the
treatment principles, methods, and techniques, along with case examples to
illustrate what we mean. Case material is taken from audio recordings for which
written informed consent was obtained for presentations and journal articles.
Some changes have been made to maintain confidentiality.
PMID- 28513343
TI - The Impact of Social Exclusion on "Reading the Mind in the Eyes" Performance in
Relation to Borderline Personality Disorder Features.
AB - In this study we used the Reading the Mind in the Eyes Test (RMET) to explore
facial emotion recognition in borderline personality disorder (BPD). We also used
Cyberball, a computerized task designed to mimic social ostracism, to examine the
response of BPD-feature participants to social exclusion. Seventeen individuals
with BPD features were compared to 16 healthy controls on RMET performance pre-
and post-exclusion via Cyberball. Our results revealed a significant interaction
between BPD-feature status and RMET performance in relation to neutral stimuli
following a social exclusion experience. BPD participants' ability to correctly
identify neutral faces significantly decreased following exclusion. This finding
suggests that once an individual with BPD features experiences a social exclusion
event, his or her objectivity decreases and affective valence is ascribed to
stimuli previously perceived as neutral. Our results may help to explain, in
part, the social instability seen in BPD.
PMID- 28513344
TI - Pathological Narcissism and Nonsuicidal Self-Injury.
AB - Few studies have examined associations between pathological narcissism and self
harm, but those that do indicate that narcissistic vulnerability (not
narcissistic grandiosity) relates to self-harm. The current study extends this
literature by investigating how facets of pathological narcissism assessed by the
Pathological Narcissism Inventory relate to specific nonsuicidal self-injury
(NSSI) behaviors assessed by the Inventory of Statements About Self-Injury using
statistical models appropriate for non-normally distributed count data. In a
sample of 1,023 undergraduate students, results revealed that facets of both
narcissistic vulnerability and narcissistic grandiosity were differentially
related to the endorsement and frequency of specific NSSI behaviors and higher
order latent NSSI factors (repetitive and impulsive), even after accounting for
levels of borderline pathology. The clinical implications of these results are
discussed.
PMID- 28513345
TI - Borderline Personality Disorder Features and Sensitivity to Injustice.
AB - Hypersensitivity to injustice has been proposed to contribute to interpersonal
dysfunction in borderline personality disorder (BPD). We investigated whether BPD
features are related to sensitivity to injustice and whether justice sensitivity
mediates the relationship between BPD features and aggressive behavior. In an
online survey, subjects reported justice sensitivity from the perspective of a
victim, an observer, a beneficiary, and a perpetrator as well as BPD features and
their own aggressive behavior. Justice sensitivity was higher in participants
with a clinically relevant degree of BPD features when they evaluated injustice
from the perspective of a victim or an observer. Victim sensitivity partially
mediated the relationship between BPD features and the frequency of aggressive
behavior. The present study provides first data on the important role of
sensitivity to injustice in those with marked BPD features. Particularly, victim
sensitivity with its close link to angry reactions may contribute to
interpersonal problems in BPD.
PMID- 28513347
TI - Development and Initial Validation of an Inconsistent Responding Scale for the
Youth Psychopathic Traits Inventory.
AB - The Youth Psychopathic Traits Inventory (YPI) is widely used in research, but
there currently exist no means to identify potentially invalid protocols
resulting from careless or random responding. We describe the development of an
inconsistent responding scale for the YPI using three archival samples of youths,
including two from the United States (juvenile justice and middle school) and one
from Germany (vocational training school). We first identified pairs of
correlated YPI items and then created a total score based on the sum of the
absolute value of the differences for each item pair. The resulting scale
strongly differentiated between genuine protocols and randomly generated YPI data
(n = 1,000) across samples (AUC values = .88-.92). It also differentiated between
genuine protocols and those same protocols after 50% of the original YPI items
were replaced with random data (AUCs = .77-.84). Scores on this scale also
demonstrated fairly consistent patterns of association with theoretically
relevant correlates.
PMID- 28513346
TI - Psychoeducation and Problem Solving (PEPS) Therapy for Adults With Personality
Disorder: A Pragmatic Randomized-Controlled Trial.
AB - We compared psychoeducation and problem solving (PEPS) therapy against usual
treatment in a multisite randomized-controlled trial. The primary outcome was
social functioning. We aimed to recruit 444 community-dwelling adults with
personality disorder; however, safety concerns led to an early cessation of
recruitment. A total of 154 people were randomized to PEPS and 152 to usual
treatment. Follow-up at 72 weeks was completed for 68%. PEPS therapy was no more
effective than usual treatment for improving social functioning (adjusted
difference in mean Social Functioning Questionnaire scores = -0.73; 95% CI [
1.83, 0.38]; p = 0.19). PEPS therapy is not an effective treatment for improving
social functioning of adults with personality disorder living in the community.
PMID- 28513348
TI - Measurement Invariance Between Genders on Two Measures of Borderline Personality
Disorder.
AB - Gender bias in the diagnosis and assessment of borderline personality disorder
(BPD) has been the subject of much controversy in the psychological research
literature. Evidence regarding differential prevalence rates and diagnostic rates
in clinical settings between genders has been mixed, and measurement bias is one
potential explanation for these mixed findings. A total of 340 participants were
recruited from a Midwestern university and four outpatient community mental
health clinics. They were administered two structured clinical interviews for BPD
that were then evaluated for measurement invariance. Both the SCID-II BPD scale
and the PDI-IV BPD scale were found to be measurement invariant between genders.
No significant differences were found on the SCID-II BPD scale in diagnosis or
overall number of criteria endorsed. However, in the rates of endorsement of
individual criteria, differences were found in the unstable relationships item.
PMID- 28513349
TI - Development and Psychometric Properties of the Standardized Assessment of
Severity of Personality Disorder (SASPD).
AB - Personality disorder (PD) is increasingly categorized according to its severity,
but there is no simple way to screen for severity according to ICD-11 criteria.
We set out to develop the Standardized Assessment of Severity of Personality
Disorder (SASPD). A total of 110 patients completed the SASPD together with a
clinical assessment of the severity of personality disorder. We examined the
predictive ability of the SASPD using the area under the ROC curve (AUC). Two to
four weeks later, 43 patients repeated the SASPD to examine reliability. The
SASPD had good predictive ability for determining mild (AUC = 0.86) and moderate
(AUC = 0.84) PD at cut points of 8 and 10, respectively. Test-retest reliability
of the SASPD was high (intraclass correlation coefficient = 0.93, 95% CI [0.88,
0.96]). The SASPD thus provides a simple, brief, and reliable indicator of the
presence of mild or moderate PD according to ICD-11 criteria.
PMID- 28513350
TI - Examining the Relationships Between the Triarchic Psychopathy Constructs and
Behavioral Deviance in a Community Sample.
AB - Few studies have examined the extent to which psychopathic traits relate to the
commission of mild to moderate acts of deviance, such as vandalism and minor
traffic violations. Given that psychopathy is now studied in community
populations, the relationship between psychopathic traits and less severe deviant
behaviors, which are more normative among noninstitutionalized samples, warrants
investigation. The current study examined the relationships between the triarchic
model of psychopathy (Patrick, Fowles & Krueger, 2009) and seven forms of deviant
behavior (drug use, alcohol use, theft, vandalism, school misconduct, assault,
and general deviance) in a nationally representative sample. Triarchic
disinhibition positively predicted each form of normative deviance. Boldness
positively predicted drug and alcohol use as well as general deviance, while
meanness negatively predicted school misconduct. Boldness and disinhibition also
positively predicted overall lifetime engagement in deviant behavior.
Implications are discussed, including support of the role of boldness within the
psychopathy construct.
PMID- 28513354
TI - Nurses' goodwill keeping NHS afloat, RCN warns.
AB - Four in five NHS nursing directors in the UK are worried that their hospitals
rely on the goodwill of staff to keep services running, according to research
from the RCN.
PMID- 28513351
TI - Mind the Fathers: Associations of Parental Childhood Adversities With Borderline
Personality Disorder Pathology in Female Adolescents.
AB - Previous research revealed significant relations between the experience of
childhood adversity (CA) and the development of borderline personality disorder
(BPD) in adulthood. However, it is still uncertain whether parental CA could have
a transgenerational association with adolescent BPD. We investigated associations
between parents' CA (antipathy, neglect, physical abuse) and BPD traits within a
clinical adolescent sample and tested for mediating variables. The sample
consists of 91 female inpatients, along with 84 mothers and 59 fathers.
Adolescent BPD traits were assessed using the BPD module of the Structured
Clinical Interview for DSM-IV Disorders (SCID-II). Adolescent and parental CA and
parental subclinical BPD traits were measured using validated self-report
questionnaires (CECA.Q; PSSI). The findings revealed significant associations
between parental CA and adolescent BPD traits, which were partially mediated by
parental subclinical BPD traits and by paternal but not maternal CA. The results
underline that early intervention of BPD must target the family environment,
including fathers.
PMID- 28513355
TI - Student-mentor friction debated.
AB - Nursing students' challenging behaviour towards mentors was the subject of a
debate at RCN congress.
PMID- 28513352
TI - What impact does antenatal and postnatal care have on neonatal deaths in low- and
lower-middle-income countries? Evidence from Bangladesh.
AB - We investigated the contribution of antenatal and postnatal care in reducing the
risk of neonatal deaths in Bangladesh. The effects of these services were
examined using adjusted Cox regression models and secondary data with 7,314 live
born infants. We observed that neonatal mortality was significantly decreased for
newborns whose mothers' attended antenatal care services but postnatal care did
not show any effect. Health promotion programs offering antenatal care in
Bangladesh and other low- and lower-middle-income countries may build awareness
about these practices. Further research is required to examine the reasons for
the lack of impact of postnatal care on mortality.
PMID- 28513356
TI - FamilyPlug.
AB - This is the first communication app for patients with severe physical
disabilities who are in an immobilised and semiconscious state. It allows the
user's voice to reach the patient to help reduce feelings of isolation.
PMID- 28513357
TI - Nursing students' experience of research during clinical placements.
AB - Aim To investigate pre-registration nursing students' experience of research
during clinical placements, and to identify any positive aspects or barriers to
gaining experience of research during clinical placements. Method Qualitative,
phenomenological, semi-structured interviews were undertaken with preregistration
degree-level nursing students. The students were attending one university in the
east of England, and were on clinical placements at one of three hospital sites
in two trusts. Data were reviewed using thematic analysis. Findings The main
themes that emerged from the interview data were: visibility, mentor influence,
placement culture, student mindset, and role of the university. The study
participants provided suggestions that could be adopted by universities and
trusts to improve nursing students' experience of research during clinical
placements, such as increasing opportunities to shadow research teams,
introducing research earlier in the pre-registration course, and including a
practical research module in the course. Conclusion Nursing students' experience
of research during their clinical placements varied. It is important for trusts
and universities to identify ways to improve nursing students' experience of
research and to enhance their research learning, since research activity drives
innovation and best practice.
PMID- 28513358
TI - Workplace violence is unacceptable.
AB - 'No one should feel threatened in the workplace for simply doing their job,' said
the newspaper report.
PMID- 28513359
TI - 'Innovations in your Specialty award winner helped save my life'.
AB - 'Diane has given me strength and courage when I had nothing more than suicidal
thoughts and, slowly but surely, she has helped me to piece together my life,'
says Simon Peacock. 'She did this by keeping her word. She believed in me. She
followed up referrals. She listened.'
PMID- 28513360
TI - Student life - Be an agent of compassion.
AB - [Figure: see text] The true definition of compassion is 'to be with suffering'.
But in reality, compassion demands much more than simply being with suffering. It
requires agency to help another get through it. Therefore, compassion requires an
agent. An agent is defined as 'a person who acts on behalf of another person',
and 'a person or thing that acts or has the power to act'.
PMID- 28513363
TI - Wales keeps a welcome for students.
AB - A campaign has been launched promoting Wales as a place for nurses to train, work
and live.
PMID- 28513361
TI - Readers' panel - Will the general election lead to a better deal for nurses?
AB - Our experts consider a hot topic of the day.
PMID- 28513364
TI - NHS Providers urges new government to address workforce shortages.
AB - Unsafe staffing levels and poor pay are compromising patient care, healthcare
providers have warned.
PMID- 28513365
TI - No safety net.
AB - What is the point of the royal family publicising mental health issues when care
services in this specialty are not there when needed?
PMID- 28513366
TI - Nurses wearing body cams.
AB - This is inconceivable in mental health settings. Can you imagine an acutely
unwell individual with paranoid and psychotic symptoms being seen by a nurse
wearing a body cam? Not to mention issues around confidentiality.
PMID- 28513367
TI - A sense of belonging unites Queen's Nurses.
AB - In 1893, Florence Nightingale said hospitals are 'only an intermediate stage of
civilization, never intended at all even to take in the whole sick population'.
PMID- 28513368
TI - Credit where it's due.
AB - Will staff in care homes ever receive thanks for their hard work and dedication?
PMID- 28513370
TI - Tick-box spirituality.
AB - The continued support for nurses in the delivery of spiritual care is to be
welcomed (opinion, 12 April; evidence & practice, 19 April). However, I remain
sceptical about the inclination to produce nursing process-type forms of
spiritual assessment. If you have to use a form to assess a patient's spiritual
needs, should you be asking at all?
PMID- 28513369
TI - Confidentiality issues.
AB - The first thing you need to do is seek approval from the relevant person at the
practice. This could be your line manager, the practice manager or one of the
partners. Once permission is in place, and if you want your son's friend to
observe you as you work, there are two main areas that could pose a problem:
patient consent and confidentiality.
PMID- 28513371
TI - Letter.
AB - There are many implications for patient dignity and confidentiality if staff wear
body cams, but if interactions are recorded it could help prevent difficult
situations from escalating.
PMID- 28513373
TI - Philip, a prince among men.
AB - Following the announcement that Prince Philip will withdraw from public duties, I
should like to place on record the gratitude of male nurses when, as patron of
the Society of Registered Male Nurses, he encouraged the career development of
men in the profession.
PMID- 28513375
TI - Helping victims of modern slavery.
AB - I was volunteering at a refugee centre when a woman told me she was the happiest
she could remember being. She said she had previously been a slave, and no matter
how bad I thought her situation was now, it was always better than her past.
PMID- 28513374
TI - Bursaries and safe staffing legislation top Corbyn's election pledges at
congress.
AB - Nursing student bursaries will be reinstated and NHS staff from the European
Union (EU) given the right to remain if Labour wins the general election, Jeremy
Corbyn has pledged.
PMID- 28513376
TI - People who speak up must be celebrated.
AB - From my own experience and conversations with other NHS whistleblowers, I am
acutely aware of the fear that can consume you before and after raising concerns.
Many health service staff believe they will lose their job, or at the very least
be prevented from progressing in their career if they speak out.
PMID- 28513377
TI - An important specialism.
AB - Inflammatory bowel disease (IBD) nurse specialists provide invaluable support and
expertise to patients to help improve their quality of life and give them more
control over their treatment.
PMID- 28513378
TI - Research identifies new way to attack breast cancer cells.
AB - A study has revealed a new method for attacking the growth of cancer cells, after
researchers discovered a protein that drives the spread of breast cancer.
PMID- 28513380
TI - Plain packaging for cigarettes 'could cut smoker numbers'.
AB - Plain cigarette packaging could reduce the number of people who smoke, research
suggests.
PMID- 28513379
TI - How to minimise the stress of relocating.
AB - When it comes to stability, security and routine, your home and your work are
vital. When you change the two at once, the stresses multiply.
PMID- 28513381
TI - Cancer Drugs Fund was not a cost-effective use of NHS funds.
AB - The NHS Cancer Drugs Fund (CDF) was not good value for patients or society and
may have led to unnecessary side effects, researchers have found.
PMID- 28513383
TI - Fructose intake in pregnancy linked to childhood obesity.
AB - A diet high in fructose-containing sugars during pregnancy or breastfeeding may
increase children's chances of developing obesity or type 2 diabetes, new
research results suggest.
PMID- 28513382
TI - Make nursing an election issue, Davies tells congress.
AB - UK-WIDE legislation on safe staffing is needed to protect patients and the
profession, RCN general secretary Janet Davies told this week's RCN congress.
PMID- 28513384
TI - Pedometer challenge.
AB - Nurses put their best feet forward for a pedometer challenge during RCN congress.
PMID- 28513385
TI - Scrap the cap or jeopardise patient safety.
AB - After the general election, for the sake of patient safety, the government must
scrap the cap on nurses' pay and help to fill the 40,000 vacant jobs. These are
not my words, but those of RCN general secretary Janet Davies, and summarise the
college's key message to the political parties in the run-up to polling day on 8
June.
PMID- 28513386
TI - 'Working with nurses in Myanmar opened my eyes'.
AB - When paediatric nurse Jennifer Sims decided in 2015 that she wanted to take on a
new career challenge overseas, she got more than she bargained for.
PMID- 28513387
TI - 'I wanted to be a Blue Peter presenter'.
AB - Ruth Butler qualified as a registered general nurse and registered sick
children's nurse in the 1980s, working at London's Great Ormond Street Hospital
for Children NHS Trust. Last year, she was crowned winner of the child health
award at the RCNi Nurse Awards, and has been in her current role as research
associate at Central London Community Healthcare NHS Trust since October 2016.
PMID- 28513388
TI - Cerebral palsy.
AB - New guidelines from the National Institute for Health and Care Excellence (NICE)
focus on children with cerebral palsy.
PMID- 28513389
TI - TB: not just a disease of the past.
AB - According to TB nurse manager Margaret Ogedengbe, getting the message across that
tuberculosis (TB) is still a real and present danger in the UK is tough, because
many people simply don't believe it.
PMID- 28513391
TI - Body cameras help to reduce violence on wards.
AB - Nurses who wore body cameras at work have praised the technology after a three
month trial.
PMID- 28513393
TI - Further study opens up career opportunities.
AB - In the 1970s, only about one in 20 nurses in the had a degree, and the necessity
of such an academic requirement was often viewed with derision. Now, as an all
graduate profession, the importance of a master's degree for career progression
takes on greater potency.
PMID- 28513395
TI - Children less physically active as they progress through school.
AB - Children spend less time doing physical activity as they progress through primary
school, research has found.
PMID- 28513396
TI - Acute pulmonary oedema.
AB - What was the nature of the CPD activity, practice-related feedback and/or event
and/or experience in your practice? The article provided information about the
pathology, recognition, assessment and management of acute pulmonary oedema.
PMID- 28513397
TI - Congress backs 'summer of protest' over pay.
AB - Nurses across the UK could be set for a historic summer of protest after an RCN
poll revealed strong support for strikes over pay restraint. The college warned
that unless the next government scraps the 1% pay cap it will hold a ballot on
industrial action later this year, threatening the first ever members' strikes in
the RCN's 100-year history.
PMID- 28513398
TI - 'Nurse believed in me and helped me piece my life back together'.
AB - While serving in the Royal Anglian Regiment in Afghanistan in 2007, I was
seriously injured by friendly fire. I was left with significant physical and
psychological injuries from the blast.
PMID- 28513399
TI - Reducing health inequalities for people with serious mental illness.
AB - People with serious mental illness (SMI) are at risk of dying many years earlier
than the general population. Providing an effective, cost-efficient healthcare
service requires a holistic approach, and improving the physical health of people
with SMI should be integral to all healthcare roles. It is important for nurses
to identify and understand the barriers that people with SMI may experience when
accessing physical healthcare. A range of factors contribute to reduced life
expectancy, including lifestyle factors, symptoms of mental illness and the side
effects of medications. This article discusses four areas of health that commonly
affect people with SMI: metabolic syndrome, smoking, oral health and sexual
health. Metabolic syndrome is a cluster of risk factors that increase an
individual's risk of cardiovascular disease, stroke and type 2 diabetes mellitus.
Smoking is increasingly prevalent in people with SMI, with rates remaining steady
despite a decline in smoking rates nationally. Oral health and sexual health can
negatively affect the physical health and well-being of people with SMI; however,
these aspects of health are often neglected. This article identifies ways that
nurses in all practice settings can use health promotion, assessment and
treatment to improve the physical health of people with SMI in relation to these
four areas.
PMID- 28513400
TI - Role of nurses in supporting patients to self-manage chronic conditions.
AB - The burden of chronic illness is increasing globally as a result of increased
life expectancy, unhealthy lifestyles, and advances in medical interventions and
treatments. Therefore, people living with chronic conditions, and their families,
will have to assume greater responsibility in managing such conditions. However,
to do so they require appropriate support from healthcare services. This article
explores some of the tensions that hinder the self-management of chronic
conditions. It emphasises the importance of individuals and their families having
the desire, and being enabled, to assume an active and decisive role in the
management of chronic conditions. Nurses have a role in enabling patients to
optimise their self-management skills, but organisational constraints in
healthcare services, as well as constraints in nurse training and nursing roles,
may mean that nurses are unable to fulfil this role. This article considers some
of the factors that may limit the development of patient and nursing roles in
relation to self-management of chronic conditions.
PMID- 28513401
TI - Brain natriuretic peptide: what the nurse needs to know.
AB - Rationale and key points Brain natriuretic peptide is a chemical secreted when
the heart is under strain. It is sampled by a blood test. This article informs
nurses about how brain natriuretic peptide can be used as a diagnostic and
prognostic marker for patients with cardiac conditions. " A brain natriuretic
peptide level within the normal range in a patient who is not receiving
treatment, almost certainly rules out a significant cardiac condition. " An
elevated brain natriuretic peptide level suggests an active cardiac condition and
further investigations are indicated, usually an electrocardiogram and
echocardiogram. " A highly elevated brain natriuretic peptide level is a marker
for a more severe prognosis.
PMID- 28513402
TI - Safeguarding Adults in Nursing Practice (Second edition) Northway Ruth Jenkins
Robert Safeguarding Adults in Nursing Practice (Second edition) 240pp L21.99
Learning Matters/Sage 9781473954847 1473954843 [Formula: see text].
AB - It is refreshing to find a book that explores nursing practice and adult
safeguarding in the manner that this one does.
PMID- 28513403
TI - Spirituality and Coping with Loss: End of Life Healthcare Practice Greenstreet
Wendy Spirituality and Coping with Loss: End of Life Healthcare Practice 160pp
L25.99 CRC Press 9781785231483 1785231480 [Formula: see text].
AB - Sometimes a book that seems at first more concerned with theory than practice can
turn out to be a fascinating and valuable text for all nurses.
PMID- 28513404
TI - [A bomb attack in the Netherlands; how would we provide hospital care?]
AB - - There is an ever-present threat of large-scale incidents and disasters, such as
terrorism and natural disasters.- Preparation and planning are the key to
successful response to major incidents and disasters, which is why education,
training sessions and exercises take place in the Netherlands.- Analysis of
recent large-scale incidents in Europe and the USA emphasises the importance of
adequate distribution of the wounded to centres where the correct care can be
provided.- A major step has been taken in the Netherlands to provide for such an
eventuality with the introduction of distribution plans for the wounded, and
other initiatives such as a regional hospital disaster plan.- If a large-scale
incident should take place the Netherlands also has a Major Incident Hospital at
its disposal; this is a unique facility that can guarantee availability of 200
spare beds to the Netherlands healthcare system within 30 minutes.
PMID- 28513405
TI - [A football player with an evident knee trauma].
AB - A 22-year-old male presented with medial sided instability of the right knee
three days after shooting a blocked ball. Physical examination, which is usually
feasible in the acute phase, showed grade 3 laxity of the superficial medial
collateral ligament. MRI confirmed a distal rupture, which needs repair within 2
weeks after onset.
PMID- 28513406
TI - [The court physician, the clergyman, a learned society and smallpox].
AB - Variolation was introduced in England in the first half of the 18th century. The
positive effects of this new method for preventing smallpox were already known in
the Netherlands around 1720, one of whom was the Dutch physician Boerhaave. In
spite of this, it took another 30 years before variolation was used in the
Netherlands. Despite receiving positive advice and information from his learned
English friends Sloane and Sherard, Boerhaave did not apply nor advise the use of
variolation. There were various arguments for this restrained approach. In 1754
Thomas Schwencke found that conditions were favourable for the introduction of
variolation in The Hague. There was support from the House of Orange-Nassau (the
current royal family in the Netherlands) and from a learned society; a highly
motivated clergyman acted as ambassador for the new technique and the court
physician Schwencke was willing to take the lead. A similar combination had
previously been effective in England, though the ambassador there was not a
clergyman but an influential noble lady.
PMID- 28513407
TI - [Cardiac resynchronization therapy: who is a candidate and who is not?]
AB - - Cardiac resynchronisation therapy (CRT) is a treatment for patients with
impaired cardiac pump function (left ventricular ejection fraction <= 35%) and a
wide QRS complex who, despite maximum tolerated medical therapy, remain
symptomatic.- In addition to reducing symptoms, CRT can reduce hospital
admissions and improve survival.- Selection of patients for CRT remains
difficult. Despite the fact that predicting and influencing success of CRT has
improved, ~30% of patients do not respond to the therapy.- Optimizing therapy and
follow-up of patients after implantation requires a multidisciplinary approach
tailored to the individual patient.- Cardiac rehabilitation with life style
advices and structured exercise training maximizes patient benefit from CRT.
PMID- 28513408
TI - [Legally capable care refuser has rights as well as responsibilities].
AB - It is hard to determine how a doctor should act when a patient with a somatic
condition refuses medical care. The Dutch law obliges a doctor to inform a
patient about his condition and the possible treatment options. This includes an
effort to reach out and make contact with the patient. But how far should a
doctor's responsibility reach when a patient refuses contact? We point out that
refusal of medical care can also be seen in the light of a patient's autonomy. We
thereby propose that falling ill gives responsibilities to a patient too, which
include making the effort to seek medical care and cooperate with treatment.
PMID- 28513409
TI - [A woman with acute bilateral vision loss].
AB - A 46-year-old woman presented to the emergency department with progressive
bilateral loss of vision followed by headache. She had been taking topiramate 25
mg daily for eight days before presentation. In the end, she was diagnosed with
topiramate-induced acute glaucoma for which she received appropriate treatment.
PMID- 28513410
TI - [What if the sperm donor has a hereditary disease? Informed consent needed for
sharing medical information].
AB - There are no regulations in the Netherlands regarding the exchange of important
genetic information that has become available after the birth of a child
conceived with donor gametes. This may lead to difficult situations such as when
the gamete donor is found to suffer from a genetic cancer-predisposition
disorder. Genetic information about the donor that becomes available later may be
of great importance to donor offspring. Genetic information uncovered in the
donor child may likewise be of importance to legal offspring of the gamete donor.
We propose an informed-consent procedure for both donors and recipients to take
better care of this issue.
PMID- 28513411
TI - [Injuries resulting from accidents and violence in the Netherlands; results of an
Emergency Department register].
AB - - Injuries from accidents and violence are amongst the most important public
health issues in the world, including in Europe and the Netherlands.- Using the
Dutch Injury Surveillance System and the Dutch Burden of Injury Model, we
describe the incidence and costs associated with injuries in the Netherlands that
are registered via Emergency Departments (ED). We also map the main causes of
injury by age category.- Annually, 700,000 patients attend the ED of a hospital
with an injury; 1 in 6 attendees is admitted.- The societal costs of these
injuries totals 3.2 billion euro per year. These costs consist of direct care
related costs and indirect costs through work absence.- Private injuries
contribute to more than half of the number of casualties. Injuries occur
relatively more often in children and the elderly.- The key underlying causes
differ per age category. Common causes in all ages are cycling accidents, falls
from heights, and other fall-related incidents.- The government should continue
to deliver the public health interventions for prevention of fall injuries and
cycling accidents.
PMID- 28513412
TI - [Multidisciplinary approach of facial injuries].
AB - BACKGROUND: Approximately one quarter of polytrauma patients has facial injuries,
which usually lead to loss of form and function. Several specialties are involved
in the acute and reconstructive phases of facial injuries, such as oral and
maxillofacial surgery, otorhinolaryngology, plastic surgery, ophthalmology and
dentistry. CASE DESCRIPTION: A 25-year-old man with severe facial injuries was
brought to the shock room after sustaining high-energy trauma. He had a panfacial
fracture that required reconstruction. This was done with two surgeries, with an
interval of 4 days. The patient recovered successfully after this. CONCLUSION:
Because of the complexity of facial trauma, many factors are involved in acute
care and treatment. It is therefore important to designate one coordinating
specialty to guide this process. The oral and maxillofacial surgeon plays a vital
role in this.
PMID- 28513413
TI - [NHG 'Traumatic wounds and bite wounds' treatment guideline].
AB - - The 'Traumatic wounds and bite wounds' treatment guideline by the NHG (Dutch
College of General Practitioners) has recommendations for treating traumatic
wounds, bite wounds and wound infection.- It is important to distinguish between
traumatic wounds and bite wounds because treatment of lacerations and cuts
differs from treatment of bites.- Clean a wound under a lukewarm water tap; avoid
using disinfectants.- Preferably close traumatic wounds within 12 hours, provided
that the wounds have been carefully cleaned and that there are no referral
indications. The strict limit of 6 hours has been abandoned because the age of
the wound does not seem to be related to increased infection risk.- Do not close
bite wounds unless there is a low estimated risk of infection, it is considered
cosmetically important, closure is possible within 8 hours, provided that the
wounds have been carefully cleaned, and there are no referral indications.
PMID- 28513414
TI - [Prehospital triage in trauma patients; ambulance care and deployment of a mobile
medical team].
AB - - The prehospital trauma triage system consisting of regional ambulance services
and overarching availability of mobile medical teams, the level criteria for
trauma centres and in-hospital care for trauma patients are well-organised in the
Netherlands.- However, the quality of prehospital triage in the Netherlands is
inadequate at the moment, with an average under-triage rate of more than 30%.
There is, thus, much room for improvement in the quality of prehospital triage.-
Research in this area is now taking off, partly because of the arrival of a new
quality indicator from the Netherlands National Health Care Institute, which
states that at least 90% of multiple-trauma patients should be primarily taken to
a level 1 trauma centre.
PMID- 28513415
TI - The Fungal Cell Wall: Structure, Biosynthesis, and Function.
AB - The molecular composition of the cell wall is critical for the biology and
ecology of each fungal species. Fungal walls are composed of matrix components
that are embedded and linked to scaffolds of fibrous load-bearing
polysaccharides. Most of the major cell wall components of fungal pathogens are
not represented in humans, other mammals, or plants, and therefore the immune
systems of animals and plants have evolved to recognize many of the conserved
elements of fungal walls. For similar reasons the enzymes that assemble fungal
cell wall components are excellent targets for antifungal chemotherapies and
fungicides. However, for fungal pathogens, the cell wall is often disguised since
key signature molecules for immune recognition are sometimes masked by
immunologically inert molecules. Cell wall damage leads to the activation of
sophisticated fail-safe mechanisms that shore up and repair walls to avoid
catastrophic breaching of the integrity of the surface. The frontiers of research
on fungal cell walls are moving from a descriptive phase defining the underlying
genes and component parts of fungal walls to more dynamic analyses of how the
various components are assembled, cross-linked, and modified in response to
environmental signals. This review therefore discusses recent advances in
research investigating the composition, synthesis, and regulation of cell walls
and how the cell wall is targeted by immune recognition systems and the design of
antifungal diagnostics and therapeutics.
PMID- 28513416
TI - The Role of ESX-1 in Mycobacterium tuberculosis Pathogenesis.
AB - In this article, we have described several cellular pathological effects caused
by the Mycobacterium tuberculosis ESX-1. The effects include induction of
necrosis, NOD2 signaling, type I interferon production, and autophagy. We then
attempted to suggest that these pathological effects are mediated by the
cytosolic access of M. tuberculosis-derived materials as a result of the
phagosome-disrupting activity of the major ESX-1 substrate ESAT-6. Such activity
of ESAT-6 is most likely due to its pore-forming activity at the membrane. The
amyloidogenic characteristic of ESAT-6 is reviewed here as a potential mechanism
of membrane pore formation. In addition to ESAT-6, the ESX-1 substrate EspB
interferes with membrane-mediated innate immune mechanisms such as efferocytosis
and autophagy, most likely through its ability to bind phospholipids. Overall,
the M. tuberculosis ESX-1 secretion system appears to be a specialized system for
the deployment of host membrane-targeting proteins, whose primary function is to
interrupt key steps in innate immune mechanisms against pathogens. Inhibitors
that block the ESX-1 system or block host factors critical for ESX-1 toxicity
have been identified and should represent attractive potential new
antituberculosis drugs.
PMID- 28513418
TI - Flagellar expression in clinical isolates of non-typeable Haemophilus influenzae.
AB - PURPOSE: Haemophilus influenzae is a commensal organism found in the upper
respiratory tract of humans. When H. influenzae becomes a pathogen, these
bacteria can move out of their commensal niche and cause multiple respiratory
tract diseases such as otitis media, sinusitis, conjunctivitis and bronchitis in
children, and chronic obstructive pulmonary disease in adults. However, H.
influenzae is currently considered a non-flagellate bacterium. METHODOLOGY AND
RESULTS: In this study, 90 clinical isolates of H. influenzae strains (typeable
and non-typeable) showed different degrees of the swarm-motility phenotype in
vitro.Keys findings. One of these strains, NTHi BUAP96, showed the highest
motility rate and its flagella were revealed using transmission electron
microscopy and Ryu staining. Moreover, the flagellar genes fliC and flgH
exhibited high homology with those of Actinobacillus pleuropneumoniae,
Escherichia coli and Shigella flexneri. Furthermore, Western blot analysis, using
anti-flagellin heterologous antibodies from E. coli, demonstrated cross-reaction
with a protein present in NTHi BUAP96. CONCLUSION: This study provides, for the
first time, information on flagellar expression in H. influenzae, representing an
important finding related to its evolution and pathogenic potential.
PMID- 28513417
TI - Carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae in HIV
infected children in Zimbabwe.
AB - BACKGROUND: Antimicrobial resistance is an emerging global health issue. Data on
the epidemiology of multidrug-resistant organisms are scarce for Africa,
especially in HIV-infected individuals who often have frequent contact with
healthcare. We investigated the prevalence of extended-spectrum beta-lactamase
producing Enterobacteriaceae (ESBL-E) carriage in stool among HIV-infected
children attending an HIV outpatient department in Harare, Zimbabwe. METHODS: We
recruited children who were stable on antiretroviral therapy (ART) attending a
HIV clinic from August 2014 to June 2015. Information was collected on antibiotic
use and hospitalization. Stool was tested for ESBL-E through combination disc
diffusion. API20E identification and antimicrobial susceptibility was performed
on the positive samples followed by whole genome sequencing. RESULTS: Stool was
collected from 175/202 (86.6 %) children. Median age was 11 [inter-quartile range
(IQR) 9-12] years. Median time on ART was 4.6 years (IQR 2.4-6.4). ESBL-Es were
found in 24/175 samples (13.7 %); 50 % of all ESBL-Es were resistant to
amoxicillin-clavulanate, 100 % to co-trimoxazole, 45.8 % to chloramphenicol, 91.6
% to ceftriaxone, 20.8 % to gentamicin and 62.5 % to ciprofloxacin. ESBL-Es
variously encoded CTX-M, OXA, TEM and SHV enzymes. The odds of ESBL-E carriage
were 8.5 times (95 % CI 2.2-32.3) higher in those on ART for less than one year
(versus longer) and 8.5 times (95 % CI 1.1-32.3) higher in those recently
hospitalized for a chest infection. CONCLUSION: We found a 13.7 % prevalence of
ESBL-E carriage in a population where ESBL-E carriage has not been described
previously. Antimicrobial resistance (AMR) in Africa merits further study,
particularly given the high HIV prevalence and limited diagnostic and therapeutic
options available.
PMID- 28513419
TI - Histological findings in severe Mycoplasma pneumoniae pneumonia.
PMID- 28513422
TI - 2017 Trauma Association of Canada Annual Scientific Meeting Abstracts.
PMID- 28513423
TI - Bethune Roundtable 2017 Abstracts.
PMID- 28513421
TI - Clinical and bacteriological characteristics associated with clustering of
multidrug-resistant tuberculosis.
AB - SETTING: The impact of the genetic characteristics of Mycobacterium tuberculosis
on the clustering of multidrug-resistant tuberculosis (MDR-TB) has not been
analyzed together with clinical and demographic characteristics. OBJECTIVE: To
determine factors associated with genotypic clustering of MDR-TB in a community
based study. DESIGN: We measured the proportion of clustered cases among MDR-TB
patients and determined the impact of clinical and demographic characteristics
and that of three M. tuberculosis genetic characteristics: lineage, drug
resistance-associated mutations, and rpoA and rpoC compensatory mutations.
RESULTS: Of 174 patients from California and Texas included in the study, the
number infected by East-Asian, Euro-American, Indo-Oceanic and East-African
Indian M. tuberculosis lineages were respectively 70 (40.2%), 69 (39.7%), 33
(19.0%) and 2 (1.1%). The most common mutations associated with isoniazid and
rifampin resistance were respectively katG S315T and rpoB S531L. Potential
compensatory mutations in rpoA and rpoC were found in 35 isolates (20.1%).
Hispanic ethnicity (OR 26.50, 95%CI 3.73-386.80), infection with an East-Asian M.
tuberculosis lineage (OR 30.00, 95%CI 4.20-462.40) and rpoB mutation S531L (OR
4.03, 95%CI 1.05-23.10) were independent factors associated with genotypic
clustering. CONCLUSION: Among the bacterial factors studied, East-Asian lineage
and rpoB S531L mutation were independently associated with genotypic clustering,
suggesting that bacterial factors have an impact on the ability of M.
tuberculosis to cause secondary cases.
PMID- 28513424
TI - A review of six methods for monitoring infliximab concentrations and antibodies
to infliximab?.
AB - Anti-TNF-alpha therapy, such as infliximab (IFX), has profoundly changed
treatment to induce and maintain remission for inflammatory bowel diseases
patients who do not respond to conventional therapies. Unfortunately, IFX, as a
chimeric protein, is potentially immunogenic, and antibodies to infliximab (ATI)
may interfere with the pharmacodynamics and pharmacokinetics of the drug, thus
resulting in a loss of response for a substantial proportion of patients. The
clinical efficacy of IFX is correlated with the levels of IFX and ATI. Therefore,
monitoring patients for the trough levels of IFX and the presence of ATI is very
important. The procedures and characteristics of six assays for monitoring IFX
and ATI are described in this review, and the comparisons between them are also
discussed. To date, there has been no optimal assay for monitoring IFX and ATI.
Therefore, many technical problems need to be solved to make therapeutic drug and
immunogenicity monitoring a part of routine clinical management.?.
PMID- 28513425
TI - Actual use of and adherence to ibuprofen 400 mg tablet dosing instructions in a
simulated OTC environment?.
AB - OBJECTIVE: Evaluate adherence of US consumers to proposed label directions for a
new 400 mg ibuprofen formulation. METHODS: In this single-arm, open-label,
multicenter, 30-day study simulating an over-the-counter (OTC)-like environment,
US analgesic consumers reviewed proposed product packaging for a new 400 mg
ibuprofen formulation and made a purchase decision. Purchasers used the product
as needed and recorded use over 30 days. Outcomes included the percentage of
participants who exhibited correct or acceptable product use for the primary
endpoint (not exceeding 1,200 mg/day > 2 times during the study) or secondary
endpoint (not exceeding 400 mg/dose > 2 times during the study) and adherence to
the labeled dosing interval of 6 - 8 hours. Primary endpoint success was met if
the lower bound of the 95% confidence interval (CI) was >= 85%. RESULTS: Of 685
purchasers providing use data, correct or acceptable use behavior occurred in
95.2% (95% CI: 93.6%, 96.8%) regarding total daily dose and in 84.4% (95% CI:
81.7%, 87.1%) regarding the number of tablets taken per dosing occasion. Most
participants (87.3%) never used > 1,200 mg/day or took > 1 tablet/dose (78.1%).
Nearly 43% of subjects re-dosed within 6 hours of the previous dose; of these, ~
82% re-dosed between the 4- and 6-hour time intervals. Adverse events were
consistent with prior ibuprofen 200 mg experience. CONCLUSION: This study
provides evidence that a majority of US consumers would be able to use OTC
ibuprofen 400 mg tablets in a manner consistent with product labeling. Misuse
rates were low and unlikely to generate an excess risk of clinically important
adverse events.?.
PMID- 28513426
TI - Pharmacokinetics and bioequivalence of a pregabalin 150-mg capsule in healthy
Thai subjects.
AB - OBJECTIVE: The purpose of the study was to evaluate the pharmacokinetics and
bioequivalence of pregabalin following administration of a 150-mg capsule of test
and reference products. METHOD: The study was designed as a randomized, two
treatment, two-period, two-sequence, single-dose crossover with 1-week washout
period between period I and period II dosing. 20 healthy male and female Thai
subjects were enrolled in the study. Each subject was in fasted state for ~ 10
hours prior to receiving a single oral 150-mg pregabalin capsule. Serial blood
samples were collected at pre-dose until 32 hours after drug administration.
Plasma samples were extracted by protein precipitation and derivatized with 4
chloro-7-nitrobenzofurazan. Pregabalin plasma concentrations were determined by
HPLC method, and pharmacokinetic parameters were calculated. For bioequivalence
assessment, the differences of Cmax, AUC0-t, and AUC0
inf means based on ln-transformed data were assessed by the 90% confidence
interval (CI). RESULTS: Pharmacokinetic parameters were determined that test and
reference products showed 0.96 +/- 0.35 and 1.04 +/- 0.96 hours for
tmax, 4,594.217 +/- 834.195 and 4,568.68 +/- 573.963 ng/mL for
Cmax, 30,048.150 +/- 2,998.920 and 29,315.722 +/- 2,747.396 ng*h/mL
for AUC0-t, 30,594.210 +/- 2,872.317 and 29,831.454 +/- 2,688.020
ng*h/mL for AUC0-inf, respectively. The 90% CIs of Cmax,
AUC0-t, and AUC0-inf for test and reference products were
assessed at 95.356 - 104.630%, 99.303 - 105.751%, and 99.373 - 105.788%,
respectively. The results were within the acceptance criteria of 80 - 125%.
CONCLUSION: Pharmacokinetic parameters of a single oral 150-mg pregabalin capsule
in healthy Thai subjects were evaluated and showed rapid absorption. 90% CI for
the differences of Cmax, AUC0-t, and AUC0-inf
were within the acceptable range of the criteria so that bioequivalence of the
test and reference products of pregabalin 150-mg capsule could be concluded.?.
PMID- 28513427
TI - Population pharmacokinetics of lyophilized recombinant glucagon-like peptide-1
receptor agonist (recombinant exendin-4, rE-4) in Chinese patients with type 2
diabetes mellitus?.
AB - OBJECTIVE: To investigate the population pharmacokinetics of lyophilized
recombinant glucagon-like peptide-1 receptor agonist (rE-4) in Chinese patients
with type 2 diabetes mellitus (T2DM) for plasma concentration estimation and
individualized treatment. METHODS: Twelve patients with T2DM were enrolled to
receive subcutaneous injections of rE-4 at 5 ug twice daily for 84 days.
Administration dosage was adjusted from 5 ug to 10 ug twice daily at day 29 in
case of glycated albumin (GA) >= 17%. The population pharmacokinetic model was
developed in the nonlinear mixed-effects modeling software NONMEM. RESULTS: The
data were best described by a two-compartment model with first-order absorption
and elimination. The outcome parameters were as follows: apparent clearance
(CL/F) 6.67 L/h, apparent distribution volume of central compartment
(Vc/F) 19.4 L, absorption rate constant (Ka) 1.39 h
1, apparent distribution volume of peripheral compartment (Vp/F)
22.6 L, intercompartmental clearance (Q/F) 1.28 L/h. The interindividual
variabilities for CL/F, Vc/F, Ka, and Q/F were 64.4%,
57.7%, 45.5%, and 153.3%, respectively. The intra-individual variability of
proportional error model was 41.7%. No covariate was screened out that showed
significant influence on the model parameters. CONCLUSIONS: The established two
compartment model with first-order absorption and elimination successfully
described the pharmacokinetic characteristics of rE-4 in Chinese patients with
T2DM.?.
PMID- 28513429
TI - Five-year publication rate of podium presentations at SICOT Annual Conference: an
observational study and new objective proposal of conference power.
AB - INTRODUCTION: The SICOT Conference Committee continually tries to improve the
quality of presentations at their annual international meetings. However to the
author's best knowledge, no previous study has been undertaken to determine
abstract quality. This study aimed to determine the five-year publication rate of
presentations made at the 2009 SICOT Annual International Conference (AIC),
recognise predictors of full-text publication, identify inconsistencies between
presentations and publications, and determine presentation-publication delay.
METHODS: We retrieved all 329 oral presentation abstracts from the 2009 SICOT
Conference, recorded fundamental study details and conducted a comprehensive,
electronic search of Medline and PubMed to determine publication status. For
subsequent publications, we examined for inconsistencies between presentation
abstracts and full-text publications, whether there were retrospectively
identifiable publication predictors and calculated presentation-publication
delay. RESULTS: The five-year publication rate for all presentations was 31.3%,
for oral presentations. The average presentation-publication delay was 23.4
months. Observational studies were the most commonly published studies.
Publications most commonly resulted from studies related to hip and knee
subspecialties. CONCLUSION: Our study shows that almost one third of all
abstracts presented at SICOT led to a full-text publication. This is a positive
outcome particularly when made in comparison to similar studies of other
reputable international conferences such as European Federation of Orthopaedics
and Traumatology (EFORT) and American Academy of Orthopaedic Surgeons (AAOS).
This study re-enforces SICOT's reputation as a world leading international
conference with a strict peer-review process yielding high-quality presentations.
PMID- 28513430
TI - Global clues to the nature of genomic mutations in humans.
AB - An analysis of worldwide human genetic variation reveals the footprints of
ancient changes in genomic mutation processes.
PMID- 28513428
TI - Slipped capital femoral epiphysis: a review of management in the hip impingement
era.
AB - Slipped capital femoral epiphysis (SCFE) remains the most common adolescent hip
disorder. Most cases present with stable slips, and in situ fixation is the most
commonly adopted treatment worldwide. The introduction of the concept of
femoroacetabular impingement and subsequent studies have revealed SCFE-related
hip impingement to be a significant pre-arthritic condition, and the previously
suggested remodeling of the proximal femur after in situ fixation has been called
into question. Complex proximal femoral osteotomies and more recently intra
articular procedures via surgical hip dislocation have been employed. The
literature is still lacking a strong evidence to undertake such aggressive
procedures. Moreover, the application of a particular procedure regarding the
nature of the slip, being stable or unstable, the degree of the slip, and the
condition of the physis has not been extensively described in the literature. The
purpose of this article is to outline the SCFE-related hip impingement, to review
the best evidence for the current treatment options for both stable and unstable
slips, and to develop an algorithm for decision making.
PMID- 28513432
TI - Keeping carbon dioxide in check.
AB - The response of the brainstem to increased levels of carbon dioxide in the blood
is coordinated with the response of the cardiovascular system.
PMID- 28513431
TI - Dissection of zebrafish shha function using site-specific targeting with a Cre
dependent genetic switch.
AB - Despite the extensive use of zebrafish as a model organism in developmental
biology and regeneration research, genetic techniques enabling conditional
analysis of gene function are limited. In this study, we generated Zwitch, a Cre
dependent invertible gene-trap cassette, enabling the establishment of
conditional alleles in zebrafish by generating intronic insertions via in vivo
homologous recombination. To demonstrate the utility of Zwitch, we generated a
conditional sonic hedgehog a (shha) allele. Homozygous shha mutants developed
normally; however, shha mutant embryos globally expressing Cre exhibited strong
reductions in endogenous shha and shha target gene mRNA levels and developmental
defects associated with null shha mutations. Analyzing a conditional shha mutant
generated using an epicardium-specific inducible Cre driver revealed unique roles
for epicardium-derived Shha in myocardial proliferation during heart development
and regeneration. Zwitch will extend the utility of zebrafish in organ
development and regeneration research and might be applicable to other model
organisms.
PMID- 28513433
TI - Distributing tasks via multiple input pathways increases cellular survival in
stress.
AB - Improving in one aspect of a task can undermine performance in another, but how
such opposing demands play out in single cells and impact on fitness is mostly
unknown. Here we study budding yeast in dynamic environments of hyperosmotic
stress and show how the corresponding signalling network increases cellular
survival both by assigning the requirements of high response speed and high
response accuracy to two separate input pathways and by having these pathways
interact to converge on Hog1, a p38 MAP kinase. Cells with only the less
accurate, reflex-like pathway are fitter in sudden stress, whereas cells with
only the slow, more accurate pathway are fitter in increasing but fluctuating
stress. Our results demonstrate that cellular signalling is vulnerable to trade
offs in performance, but that these trade-offs can be mitigated by assigning the
opposing tasks to different signalling subnetworks. Such division of labour could
function broadly within cellular signal transduction.
PMID- 28513436
TI - Drowning: a silent killer.
PMID- 28513437
TI - UK air pollution and public health.
PMID- 28513439
TI - Offline: The message of mental health.
PMID- 28513434
TI - A unifying mechanism for the biogenesis of membrane proteins co-operatively
integrated by the Sec and Tat pathways.
AB - The majority of multi-spanning membrane proteins are co-translationally inserted
into the bilayer by the Sec pathway. An important subset of membrane proteins
have globular, cofactor-containing extracytoplasmic domains requiring the dual
action of the co-translational Sec and post-translational Tat pathways for
integration. Here, we identify further unexplored families of membrane proteins
that are dual Sec-Tat-targeted. We establish that a predicted heme-molybdenum
cofactor-containing protein, and a complex polyferredoxin, each require the
concerted action of two translocases for their assembly. We determine that the
mechanism of handover from Sec to Tat pathway requires the relatively low
hydrophobicity of the Tat-dependent transmembrane domain. This, coupled with the
presence of C-terminal positive charges, results in abortive insertion of this
transmembrane domain by the Sec pathway and its subsequent release at the
cytoplasmic side of the membrane. Together, our data points to a simple unifying
mechanism governing the assembly of dual targeted membrane proteins.
PMID- 28513438
TI - Improving access to biosimilars in low-income countries.
PMID- 28513435
TI - A bioactive peptide amidating enzyme is required for ciliogenesis.
AB - The pathways controlling cilium biogenesis in different cell types have not been
fully elucidated. We recently identified peptidylglycine alpha-amidating
monooxygenase (PAM), an enzyme required for generating amidated bioactive
signaling peptides, in Chlamydomonas and mammalian cilia. Here, we show that PAM
is required for the normal assembly of motile and primary cilia in Chlamydomonas,
planaria and mice. Chlamydomonas PAM knockdown lines failed to assemble cilia
beyond the transition zone, had abnormal Golgi architecture and altered levels of
cilia assembly components. Decreased PAM gene expression reduced motile ciliary
density on the ventral surface of planaria and resulted in the appearance of
cytosolic axonemes lacking a ciliary membrane. The architecture of primary cilia
on neuroepithelial cells in Pam-/- mouse embryos was also aberrant. Our data
suggest that PAM activity and alterations in post-Golgi trafficking contribute to
the observed ciliogenesis defects and provide an unanticipated, highly conserved
link between PAM, amidation and ciliary assembly.
PMID- 28513440
TI - Luca Richeldi: high hopes for rare lung diseases.
PMID- 28513441
TI - The art of transplantation: Mend the Living.
PMID- 28513442
TI - Digitising the mind.
PMID- 28513443
TI - Health economics.
PMID- 28513444
TI - Essential medicines for universal health coverage.
PMID- 28513445
TI - Health economics - Authors' reply.
PMID- 28513446
TI - Health economics.
PMID- 28513447
TI - Essential medicines for universal health coverage - Authors' reply.
PMID- 28513448
TI - Child poverty: no future?
PMID- 28513449
TI - No psychotherapy monoculture for anxiety disorders.
PMID- 28513451
TI - Department of Error.
PMID- 28513450
TI - No psychotherapy monoculture for anxiety disorders - Authors' reply.
PMID- 28513452
TI - Department of Error.
PMID- 28513453
TI - Chronic obstructive pulmonary disease.
AB - Chronic obstructive pulmonary disease (COPD) kills more than 3 million people
worldwide every year. Despite progress in the treatment of symptoms and
prevention of acute exacerbations, few advances have been made to ameliorate
disease progression or affect mortality. A better understanding of the complex
disease mechanisms resulting in COPD is needed. Smoking cessation programmes,
increasing physical activity, and early detection and treatment of comorbidities
are further key components to reduce the burden of the disease. However, without
a global political and economic effort to reduce tobacco use, to regulate
environmental exposure, and to find alternatives to the massive use of biomass
fuel, COPD will remain a major health-care problem for decades to come.
PMID- 28513454
TI - Lysosomal dysfunction in neurodegenerative diseases.
AB - Dane literaturowe z ostatnich lat jednoznacznie wskazuja na udzial lizosomow w
programowanej smierci komorki. Dysfunkcje lizosomow uposledzaja fuzje
autofagosomow z lizosomami, co prowadzi do wakuolizacji cytoplazmy. Obecnosc
wakuoli autofagalnych obladowanych uszkodzonymi organellami i nieprawidlowymi
bialkami jest cecha charakterystyczna wielu chorob neurodegeneracyjnych.
Agregacja niezdegradowanego materialu zaburza homeostaze komorki powodujac smierc
neuronu w wyniku apoptozy i/lub nekrozy. Ponadto indukowany kalpainami lub
spowodowany mutacjami rozpad blony lizosomu uwalnia katepsyny, ktore indukuja
szlak smierci komorki. W artykule przedstawiono mechanizm smierci komorki
nerwowej, laczacy zaburzenie szlaku autofagalno-lizosomalnego z dysfunkcjami
lizosomow, zwany lizosomalnym szlakiem smierci neuronu.
PMID- 28513455
TI - Glucose tolerance disorders during treatment with glucocorticoids in patients
with inflammatory diseases of the musculoskeletal system - based on the analysis
of data from the literature and own research results.
AB - Glucocorticoids are among the most frequently used anti-inflammatory and
immunosuppressive drugs. They are widely used in the treatment of numerous
autoimmune disorders. However, the treatment with glucocorticoids is connected
with the risk of a number of side effects. Among them, glucose tolerance
disorders play an important role. The results of meta-analyses show that the risk
of diabetes is from 1.4 to 2.5 times higher in the case of treated patients in
comparison to the general population. Glucocorticoids can directly impair
pancreatic beta-cell secretion. Nevertheless, a crucial role in the hyperglycemic
activity seems to be played by a peripheral glucose uptake reduction, principally
in the skeletal muscle, which is responsible for the decrease of insulin
sensitivity, and can manifest itself in the increase of postprandial blood
glucose levels. If they are used in higher doses and for a prolonged period, they
can also reduce the inhibitory effect of insulin on hepatic glucose production,
which can lead to an increase of fasting plasma glucose. Numerous literature data
indicate that in the case of patients who suffer from inflammatory diseases of
the musculoskeletal system, the treatment with low to moderate doses of
glucocorticoids, for a short period, does not significantly increase the
metabolic risk. The beneficial role in this area may be connected with an anti
inflammatory and immunosuppressive effect. The regular assessment of the
postprandial glucose, especially in the afternoon and evening, has the highest
diagnostic sensitivity of glucocorticoid-induced glucose tolerance disorders. In
the case of patients without a prior diagnosis of diabetes, after discontinuation
of treatment, the oral glucose tolerance test should be considered in order to
identify the presence of persistent disorders.
PMID- 28513456
TI - Aflatoxins: characteristics and impact on human health.
AB - Some molds commonly occurring in the natural environment produce mycotoxins in
the process of secondary metabolism. Aspergillus flavus and A. parasiticus are
species of molds, which are responsible for the production of aflatoxins and are
crucial in the pathogenesis of human diseases. Aspergillus species present in
decaying plants, the soil and their spores are transferred via air currents and
insects to crops and food storages. Aflatoxins B1, B2, G1, G2, M1 and M2 are the
most common derivatives of aflatoxins. Ingestion of contaminated food is the main
source of exposure to aflatoxins, which adversely affect the health of both
humans and animals. The compounds can cause acute or chronic toxic effects of a
teratogenic, mutagenic, carcinogenic, immunotoxic or hepatotoxic character.
Molecular aflatoxins affect DNA mutations, postranslation peptids chains
modification, proteins and nucleic acids methylation and the formation of free
radicals. Due to aflatoxins carcinogenic features and frequent occurrence in food
and forages they are routinely examinated in some groceries and agricultural
products.
PMID- 28513457
TI - Bacteriocins from lactic acid bacteria as an alternative to antibiotics.
AB - Bacteriocins are ribosomally synthesized, proteinaceous substances that inhibit
the growth of closely related species through numerous mechanisms. The
classification system used in this review divided bacteriocins into four sub
groups based on their size. Currently, there is extensive research focused on
bacteriocins and their usage as a food preservative. The increasing incidence of
multidrug resistant bacterial pathogens is one of the most pressing medical
problems in recent years. Recently, the potential clinical application of LAB
(Lactic Acid Bacteria) bacteriocin has been the subject of investigations by many
scientists. Bacteriocins can be considered in a sense as antibiotic, although
they differ from conventional antibiotics in numerous aspects. The gene-encoded
nature of bacteriocins makes them easily amenable through bioengineering to
either increase their activity or specify target microorganism. Owing to this
feature of bacteriocins, antibiotic therapy would become less damaging to the
natural gut microflora, which is a common drawback of conventional antibiotic
use. Bacteriocins from lactic acid bacteria represent one of the most studied
microbial defense systems and the idea of subjecting them to bioengineering to
either increase antimicrobial activity or further specify their target
microorganism is now a rapidly expanding field. This review aimed to present
bacteriocins as a possible alternative to conventional antibiotics basic on
latest scientific data.
PMID- 28513458
TI - Cofilin - a protein controlling dynamics of actin filaments.
AB - Cofilins are evolutionary conserved proteins present in all Eukaryotic cells.
Their primary function is dynamic reorganization of actin cytoskeleton. Two
cofilin isoforms are known: cofilin 1, present in all studied non-muscle cells
and in embryonic muscle cells, and cofilin 2, which dominates in mature skeletal
and cardiac muscles. Polypeptide chains of both isoforms fold into a structure
homological to a conservative ADF (actin depolymerizing factor) domain, which is
characteristic of actin depolymerizing factor. In cofilin molecule two actin
binding sites were found. One site binds monomeric and filamentous actin, the
second one interacts only with the filament. Binding of cofilin to actin filament
causes a change in the orientation of subunits, which results in filament
severing. This increases number of ends which can either elongate or shorten the
filament, depending on the conditions. Cofilin interactions with monomeric actin
decreases availability of polymerization-competent actin subunits. Cofilin
activity is controlled by phosphorylation, binding membrane phospholipids, local
pH and oxidative stress. Under conditions of oxidative stress oxidation of
cysteine residues leads to formation of dimers, which are able to cross-link
actin filaments. Stable actin-cofilin rods save cellular ATP, which is not used
during active polymerization process. This facilitates faster cell recovery from
the stress. The final cellular reaction on the environmental stimuli is a
resultant of cofilin activity and activities of other actin-binding proteins,
which function either synergistically or antagonistically. Due to the central
role in the regulation of actin filaments dynamics, cofilin is involved in
development of cancer, neurodegenerative diseases, congenital myopathies and
cardiomyopathies.
PMID- 28513459
TI - Effects of Granulocyte Colony-Stimulating Factor on Opsonin Receptor Expression
and Neutrophil Antibacterial Activity in a Mouse Model of Severe Acute
Pancreatitis.
AB - The antimicrobial function of neutrophils, which is dependent on opsonin
receptors, deteriorates in severe acute pancreatitis (SAP). Granulocyte colony
stimulating factor (G-CSF) putatively enhanced levels of the opsonin receptors
CD11b and CD32/16 in healthy human subjects, and provided protection against
infection in animal models of SAP. A statistically convincing study of the effect
of G-CSF on CD32/16 expression in an SAP model is lacking. We used a mouse model
of SAP to investigate the association between G-CSF administration and CD32/16
levels on neutrophils and bacterial translocation. G-CSF or saline was
subcutaneously injected into SAP-induced mice. The pancreases were histologically
examined, and leukocytes were stained to count neutrophils. The expression of
CD11b and CD32/16 on neutrophils was measured by flow cytometry, and bacterial
translocation was observed by bacterial culture. The numbers of CD11b and CD32/16
positive neutrophils were significantly elevated in the SAP mice treated with G
CSF, and the mean fluorescence intensities of these receptors on neutrophils were
significantly elevated. Bacterial translocations to cavity organs were suppressed
from 17% to 6% by G-CSF treatment. Our results indicated that the number of
neutrophils significantly increased with increasing expression of CD11b and
CD32/16 and their mean fluorescence intensities (MFIs). This inhibited bacterial
translocation to other organs. These results are in accord with other studies in
SAP dogs and SAP mice. Our findings suggest that G-CSF was effective in
protecting against bacterial infection in SAP mice.
PMID- 28513460
TI - The role of oxidative stress in female infertility and in vitro fertilization.
AB - Infertility problem involves many couples of reproductive age. It has been
estimated that in Poland 0.7-1.0 million pairs require treatment, while for more
than half of them assisted reproduction is the only recommended and effective
method. Infertility affects 13 to 15% of the world's population. A major concern
is the age-related decline in female fertility even more that often a decision
about pregnancy is taken at later age. Recent studies show that increased
production of reactive oxygen species is an important factor in etiopathogenesis
of pregnancy and affects female reproduction. It was found that oxidative stress
may damage the oocytes and may impair their fertilization capacity. Oxidative
stress may also lead to embryo fragmentation and formation of numerous
developmental abnormalities, and is regarded to be one of the important reasons
of spontaneous and recurrent miscarriage. Moreover, overproduction of reactive
oxygen species has a significant impact on the success of in vitro fertilization
(IVF).
PMID- 28513461
TI - The importance of Bordetella pertussis strains which do not produce virulence
factors in the epidemiology of pertussis.
AB - Bordetella pertussis strains, which have lost the ability to produce antigens,
such as pertactin - Prn, pertussis toxin - Ptx, filamentous haemagglutinin - FHA,
fimbriae type 2 and 3 - Fim 2 and 3, tracheal colonization factor - TcfA, have
recently been isolated in countries with a high vaccination coverage. The
emergence of such isolates might have resulted from B. pertussis natural
evolution course or adaptive mechanisms, allowing increased circulation of the
pathogen in vaccinated populations. So far, the majority of described mutants
were deficient in the Prn production. Prn deficient isolates were found in
countries which use acellular pertussis vaccines (aP) in routine immunization
programmes. The increase of frequency of Prn- strains isolation was correlated
with the period of routine vaccination with aP vaccines. In most countries, the
spread of these isolates has resulted from independent mutations rather than from
the expansion of a single clone. Prn- isolates were collected from patients
showing typical clinical symptoms of pertussis found for Prn+ strains. Results of
in vitro and in vivo studies have shown that Prn-, Ptx- and FHA- isolates retain
cytotoxic properties, and besides Ptx- isolates, were lethal in intranasally
infected mice. Further explanation of the impact of antigen deficiencies on
virulence and transmission of B. pertussis in the context of the continuous
increase of pertussis incidence is necessary to develop a new, optimized strategy
of pertussis prevention.
PMID- 28513462
TI - Invasion and metastasis of tumour cells resistant to chemotherapy.
AB - Metastatic tumours resistant to chemotherapy are the major cause of the clinical
failure in the treatment of malignant diseases. It is observed often that drugs
active against primary tumours do not exhibit the same efficacy towards
metastatic tumour cells having modified signaling pathways. Among cellular
factors involved in the development of the metastatic potential of multidrug
resistant tumour cells are some oncoproteins, antiapoptotic proteins, mutated
suppressor proteins, integrins and CD44 receptor. It was also demonstrated that
numerous chemotherapeutics have the effect on the emergence of the metastatic
potential and multidrug resistance (MDR) phenomenon of tumour cells. The results
of numerous studies suggest that genes involved in the development of MDR and
metastatic phenotype of tumour cells are regulated by the same signaling
pathways. They lead to the activation of transcription factors e.g. HIF-1alpha,
NF-kappaB, Ets1 and AP-1 controlling the expression of genes involved in the
development of the metastatic potential of multidrug resistant tumour cells. The
identification of key cellular factors responsible for the emergence of the
metastatic potential of MDR tumour cells could lead to the development of new
efficient strategies for the treatment of metastatic tumours resistant to the
conventional chemotherapy.
PMID- 28513463
TI - Alzheimer's disease against peptides products of enzymatic cleavage APP protein:
Biological, pathobiological and physico-chemical properties of fibrillating
peptides.
AB - Various peptides products of enzymatic cleavage of key for Alzheimer's disease
Amyloid Precursor Protein (APP) are well known, but still are matter of
scientific debate. The Abeta type products are especially challenging for
experimental and medical research. This paper outlines several, still poorly
known, biological and medical processes such as peptides biology, i.e.,
formation, biodistribution, translocation, transport and finally removal from
brain compartments and body fluids like Intracellular Fluid (ICF), Cerebrospinal
Fluid (CSF), Interstitial Fluid (ISF), blood serum or urine. In addition, the
following studies concerning AD patients might prove challenging and
simultaneously promising: peptides translocation through Blood-Brain - Barrier
(BBB) and Blood-Cerebrospinal Fluid Barrier (BCSFB) and their removal from the
brain according to a new concept of glymphatic system; - diagnostic difficulties
that stem from physico-chemical properties and the nature of proteins or
fibrillating peptides itself like low concentration, short half-live and from
experimental-technical problems as well like high adsorption or low solubility of
Abeta, tau or amylin. The study of diagnostic parameters is very important, as it
may better reflect early changes before the disease develops; one such parameter
is the Abeta42/Abeta40 ratio, or the ratio with the total tau concentration
combination and other new biomarkers like Abeta1-38; other factors include
oxidative stress and inflammation process proteins, complement factor H, alpha-2
macroglobulin, or clusterin. The study of various forms of pathological amyloid
deposits that emerge in different but specific brain regions AD patients seems to
be crucial as well. The composition of the first initial pathological, pre
fibrillating monomers of fibrillating peptides and their role in AD development
and disease progression have been described as well. They are even more
challenging for science and simultaneously might be more promising in early
diagnosis for AD patients. As always in science, research leads to endless
discoveries and further inquiry. Fundamental problems in this field most probably
are still far from being definitively comprehended, and multiple crucial
questions await better answers. What we really need is to study more and deeper
into this matter.
PMID- 28513464
TI - Pharmacological features of osthole.
AB - Coumarins are a group of naturally occurring compounds common in the plant world.
These substances and their derivatives exhibit a broad range of biological
activities. One of the naturally occurring coumarins is osthole, which can most
frequently be found in plants of the Apiaceae family. Cnidium monnieri (L.)
Cusson ex Juss. Angelica pubescens Maxim. and Peucedanum ostruthium (L.). It has
anti-proliferative, anti-inflammatory, anti-convulsant, and antiallergic
properties; apart from that, inhibition of platelet aggregation has also been
proved. The impact of osthole on bone metabolism has been demonstrated; also its
hepatoprotective and neuroprotective properties have been confirmed. The
inhibitory effect of this metokcompound on the development of neurodegenerative
diseases has been proved in experimental models. Anticancer features of osthole
have been also demonstrated both in vitro on different cell lines, and in vivo
using animals xenografts. Osthole inhibited proliferation, motility and
invasiveness of tumor cells, which may be associated with the induction of
apoptosis and cell cycle slowdown. The exact molecular mechanism of osthole anti
cancer mode of action has not been fully elucidated. A synergistic effect of
osthole with other anti-tumor substances has been also reported. Modification of
its chemical structure led to the synthesis of many derivatives with significant
anticancer effects. To sum up, osthole is an interesting therapeutic option, due
to both its direct effect on tumor cells, as well as its neuroprotective or anti
inflammatory properties. Thus, there is a chance to use osthole or its synthetic
derivatives in the treatment of cancer.
PMID- 28513466
TI - Non-small cell lung cancer - mutations, targeted and combination therapy.
AB - Year after year, a growing number of cases of non-small cell lung cancer (NSCLC),
mostly caused by smoking, have been noted. Most patients die because of the late
detection of cancer and tumor resistance to treatment with cytostatics. Treatment
of patients with advanced NSCLC is impeded by the low sensitivity of the tumor to
cytostatic agents and the co-existence of many diseases, which substrate is, like
lung cancer, cigarette smoking. Along with the development of molecular biology,
targeted therapy has started to be used, affecting specific signaling pathways
involved in the processes of oncogenesis. Compounds that inhibit the activity of
receptor tyrosine kinases are very well examined and already used in clinical
practice. NSCLC is characterized by multiple mutations, including EGFR (epidermal
growth factor receptor) and KRAS. Rarer but clinically significant is the
rearrangement of the ALK gene. Currently, for NSCLC treatment a number of EGFR
inhibitors such as erlotinib, gefitinib, afatinib and two compounds targeted in
ALK kinase crizotinib and ceritinib are applied. Unfortunately, despite numerous
studies, we are still not able to improve the treatment effectiveness of patients
with KRAS mutations. The most efficient solution would be to use a combination of
the compounds exhibiting synergistic effects on tumor cells. The literature data
describes numerous examples of the combination treatment of NSCLC cells. Some
combinations of compounds are already in clinical trials. Most attempts relate to
tyrosine kinase inhibitors in combination with other types of pharmacologic
inhibitor or immunotherapy. This paper describes the mutations occurring in NSCLC
and drugs used in clinical practice as well as being in preclinical development.
PMID- 28513465
TI - The role of SRSF1 in cancer.
AB - SRSF1 jest wielofunkcyjnym bialkiem bioracym udzial w procesach zwiazanych z
metabolizmem RNA. Nastepstwem zaburzen ekspresji SRSF1, obserwowanych w wielu
typach nowotworow, sa nieprawidlowosci w skladaniu pre-mRNA, zmiany stabilnosci
transkryptow i poziomu translacji onkogenow oraz genow supresorowych. Regulujac
roznicowe skladanie transkryptow genow CCND1, RAC1, KLF6, BCL2L1, MCL1 oraz
CASP9, SRSF1 indukuje zmiany w cyklu komorkowym, proliferacji i apoptozie.
Czynnik SRSF1 wplywa takze na angiogeneze nowotworowa i przerzutowanie, m.in.
promujac powstawanie proangiogennych wariantow VEGF oraz wariantu splicingowego
genu RON, ktory aktywuje proces przejscia nablonkowo-mezenchymalnego. Ze wzgledu
na istotna role SRSF1 w rozwoju i progresji nowotworow, bialko to jest
obiecujacym celem terapii przeciwnowotworowych wykorzystujacych zwiazki hamujace
jego aktywnosc. W artykule przedstawiono najnowsze informacje o wplywie SRSF1 na
nowotworzenie oraz jego potencjalne znaczenie w opracowaniu nowych strategii w
leczeniu chorych z nowotworami.
PMID- 28513467
TI - Evolution of the Fermi surface of BiTeCl with pressure.
AB - We report measurements of Shubnikov-de Haas oscillations in the giant Rashba
semiconductor BiTeCl under applied pressures up to ~2.5 GPa. We observe two
distinct oscillation frequencies, corresponding to the Rashba-split inner and
outer Fermi surfaces. BiTeCl has a conduction band bottom that is split into two
sub-bands due to the strong Rashba coupling, resulting in two spin-polarized
conduction bands as well as a Dirac point. Our results suggest that the chemical
potential lies above this Dirac point, giving rise to two Fermi surfaces. We use
a simple two-band model to understand the pressure dependence of our sample
parameters. Comparing our results on BiTeCl to previous results on BiTeI, we
observe similar trends in both the chemical potential and the Rashba splitting
with pressure.
PMID- 28513468
TI - Structural evolution during calcination and sintering of a (La0.6Sr0.4)0.99CoO3
delta nanofiber prepared by electrospinning.
AB - Design of three-dimensional metal oxide nanofibers by electrospinning is being
widely explored. However, the impacts of calcination and sintering on the
resulting morphology remain unknown. For the first time, (La0.6Sr0.4)0.99CoO3
delta (LSC) nanofiber, which is among the most promising electrode materials for
solid oxide fuel cells, was synthesized by sol-gel electrospinning. By elevating
the temperature in oxygen using in situ transmission electron microscopy, we
discovered the structural transitions from nanofibers to nanotubes and then to
nano-pearl strings. This facile and up-scalable method can be widely applied to
design metal oxide one-dimensional nanomaterials with precise control in both
geometry (nanofiber, nanotube and nano-pearl string) and surface area (by varying
grain size).
PMID- 28513469
TI - Amplified excited state intramolecular proton transfer fluorescence of butterfly
shaped bis-2,6-dibenzothiazolylphenol.
AB - A butterfly-shaped benzothiazole derivative, bis-2,6-dibenzothiazolylphenol (2),
was synthesized via 4-methylene bridging two 2,6-dibenzothiazolylphenol (1)
molecules, and the excited-state intramolecular proton transfer (ESIPT)
fluorescence of 1 and 2 were comparably investigated by steady-state
spectroscopic experiments with the aid of theoretical simulations for structure
and energy. It was found that 2 showed similar ESIPT emissions to those of 1 in
solution and solid states, but the ESIPT fluorescence quantum yield was
substantially amplified in the case of the more 'integrated' 2. In both
tetrahydrofuran (THF) and CHCl3 solvents, ESIPT occurred and orange emissions at
580-590 nm from keto tautomers were observed, where the absolute fluorescence
quantum yield was measured to be 0.28 and 0.41 for 1, as well as 0.41 and 0.59
for 2, respectively. In the solid state, 2 showed an ESIPT emission at 570 nm
with an absolute fluorescence quantum yield of 0.38, which is substantially
shorter and larger than the corresponding values of 1 (592 nm and 0.26)
respectively. Furthermore, both 2 and 1 showed strongly blue-shifted green
emissions around 520 nm from the deprotonated anion species in N,N-dimethyl
formamide (DMF). A similar blue-shifted green emission was also found with the
addition of fluoride in the THF solution of 2 or 1, suggesting that the
competitive deprotonation makes the ESIPT impossible.
PMID- 28513470
TI - Phase diagram of the Shastry-Sutherland Kondo lattice model with classical
localized spins: a variational calculation study.
AB - We study the Shastry-Sutherland Kondo lattice model with additional
Dzyaloshinskii-Moriya (DM) interactions, exploring the possible magnetic phases
in its multi-dimensional parameter space. Treating the local moments as classical
spins and using a variational ansatz, we identify the parameter ranges over which
various common magnetic orderings are potentially stabilized. Our results reveal
that the competing interactions result in a heightened susceptibility towards a
wide range of spin configurations including longitudinal ferromagnetic and
antiferromagnetic order, coplanar flux configurations and most interestingly,
multiple non-coplanar configurations including a novel canted-flux state as the
different Hamiltonian parameters like electron density, interaction strengths and
degree of frustration are varied. The non-coplanar and non-collinear magnetic
ordering of localized spins behave like emergent electromagnetic fields and drive
unusual transport and electronic phenomena.
PMID- 28513471
TI - Dual-functional aniline-assisted wet-chemical synthesis of bismuth telluride
nanoplatelets and their thermoelectric performance.
AB - The wet-chemical approach is of great significance for the synthesis of two
dimensional (2D) bismuth telluride nanoplatelets as a potential thermoelectric
(TE) material. Herein, we proposed a simple and effective solution method with
the assistance of aniline for the fabrication of bismuth telluride nanoplatelets
at a low temperature of 100 degrees C. The choice of aniline with its dual
function avoided the simultaneous use of a capping regent and a toxic reductant.
The as-synthesized nanoplatelets have a large size of more than 900 * 500 nm2 and
a small thickness of 15.4 nm. The growth of bismuth telluride nanoplatelets are
related to the Bi/Te ratio of precursors indicating that a larger content of the
Bi precursor is more conducive to the formation of 2D nanoplatelets. The bismuth
telluride nanoplatelets pressed into a pellet show a smaller electrical
resistivity (~6.5 * 10-3 Omega . m) and a larger Seebeck coefficient (-135 MUV K
1), as well as a lower thermal conductivity (0.27 W m-1 K-1) than those of
nanoparticles. The next goal is to further reduce the electrical resistivity and
optimize the TE performance by disposing of the residual reactant of aniline
adsorbed on the surface of the nanoplatelets.
PMID- 28513472
TI - Experimental and numerical studies of beetle-inspired flapping wing in hovering
flight.
AB - In this paper, we measure unsteady forces and visualize 3D vortices around a
beetle-like flapping wing model in hovering flight by experiment and numerical
simulation. The measurement of unsteady forces and flow patterns around the wing
were conducted using a dynamically scaled wing model in the mineral-oil tank. The
wing kinematics were directly derived from the experiment of a real beetle. The
3D flow structures of the flapping wing were captured by using air bubble
visualization while forces were measured by a sensor attached at the wing base.
In comparison, the size and topology of spiral leading edge vortex, trailing edge
vortex and tip vortex are well matched from experimental and numerical studies.
In addition, the time history of forces calculated from numerical simulation is
also similar to that from theforce measurement. A difference of average force is
in order of 10 percent. The results indicate that the leading edge vortex due to
rotational acceleration at the end of the stroke during flapping wing causes
significant reduction of lift. The present study provides useful information on
hover flight to develop a beetle-like flapping wing Micro Air Vehicle.
PMID- 28513473
TI - A density functional approach to ferrogels.
AB - Ferrogels consist of magnetic colloidal particles embedded in an elastic polymer
matrix. As a consequence, their structural and rheological properties are
governed by a competition between magnetic particle-particle interactions and
mechanical matrix elasticity. Typically, the particles are permanently fixed
within the matrix, which makes them distinguishable by their positions. Over
time, particle neighbors do not change due to the fixation by the matrix. Here we
present a classical density functional approach for such ferrogels. We map the
elastic matrix-induced interactions between neighboring colloidal particles
distinguishable by their positions onto effective pairwise interactions between
indistinguishable particles similar to a 'pairwise pseudopotential'. Using Monte
Carlo computer simulations, we demonstrate for one-dimensional dipole-spring
models of ferrogels that this mapping is justified. We then use the
pseudopotential as an input into classical density functional theory of
inhomogeneous fluids and predict the bulk elastic modulus of the ferrogel under
various conditions. In addition, we propose the use of an 'external
pseudopotential' when one switches from the viewpoint of a one-dimensional dipole
spring object to a one-dimensional chain embedded in an infinitely extended bulk
matrix. Our mapping approach paves the way to describe various inhomogeneous
situations of ferrogels using classical density functional concepts of
inhomogeneous fluids.
PMID- 28513474
TI - Dielectric analysis based on spherical-shell model for cationic and anionic
spherical polyelectrolyte brushes.
AB - We report here a dielectric study on cationic and anionic spherical
polyelectrolyte brush (SPB) (consisting of a polystyrene (PS) core and poly (2
aminoethylmethacrylate hydrochloride (PAEMH) chains or poly (acrylic acid) (PAA)
chains grafted onto the core) suspensions over a frequency range of 40 Hz-110
MHz. The relaxation behavior of the suspensions shows significant changes in the
brush layer properties when changing the particle mass fraction or pH of the
system. After eliminating the electrode polarization effect at a low frequency,
two definite relaxations related to interfacial polarization, around 100 kHz and
10 MHz respectively, are observed. Based on a single layer spherical-shell model,
we developed a curve-fitting procedure to analyze such dielectric spectra for
soft particles, and then calculated the dielectric properties of the components
of the SPBs (such as the permittivities and conductivities of the layer and
solution phase), especially the layer thickness d s of the polyelectrolyte chain
(PE) layer. We also found a larger confinement degree of counterions in the PAEMH
brush due to the protonation of the amino group. Moreover, the repulsive force
between the SPB particles is evaluated by using the d s combined with the
relative theoretical formulas. We conclude that by raising (reducing) the acidity
of the system, the stability of the PAEMH-SPB (PAA-SPB) suspension was improved.
An increase in particle concentration can also improve the stability of these two
dispersions.
PMID- 28513475
TI - Self-assembling graphene-anthraquinone-2-sulphonate supramolecular nanostructures
with enhanced energy density for supercapacitors.
AB - Boosting the energy density of capacitive energy storage devices remains a
crucial issue for facilitating applications. Herein, we report a graphene
anthraquinone supramolecular nanostructure by self-assembly for supercapacitors.
The sulfonated anthraquinone exhibits high water solubility, a pi-conjugated
structure and redox active features, which not only serve as a spacer to interact
with and stabilize graphene but also introduce extra pseudocapacitance
contributions. The formed nest-like three-dimensional (3D) nanostructure with
further hydrothermal treatment enhances the accessibility of ion transfer and
exposes the redox-active quinone groups in the electrolytes. A fabricated all
solid-state flexible symmetric device delivers a high specific capacitance of
398.5 F g-1 at 1 A g-1 (1.5 times higher than graphene), superior energy density
(52.24 Wh kg-1 at about 1 kW kg-1) and good stability (82% capacitance retention
after 10 000 cycles).
PMID- 28513476
TI - The influence of magnetic order on the magnetoresistance anisotropy of Fe1 +
delta-x Cu x Te.
AB - We performed resistance measurements on [Formula: see text]Cu x Te with [Formula:
see text] in the presence of in-plane applied magnetic fields, revealing a
resistance anisotropy that can be induced at a temperature far below the
structural and magnetic zero-field transition temperatures. The observed
resistance anisotropy strongly depends on the field orientation with respect to
the crystallographic axes, as well as on the field-cooling history. Our results
imply a correlation between the observed features and the low-temperature
magnetic order. Hysteresis in the angle-dependence indicates a strong pinning of
the magnetic order within a temperature range that varies with the Cu content.
The resistance anisotropy vanishes at different temperatures depending on whether
an external magnetic field or a remnant field is present: the closing temperature
is higher in the presence of an external field. For [Formula: see text] the
resistance anisotropy closes above the structural transition, at the same
temperature at which the zero-field short-range magnetic order disappears and the
sample becomes paramagnetic. Thus we suggest that under an external magnetic
field the resistance anisotropy mirrors the magnetic order parameter. We discuss
similarities to nematic order observed in other iron pnictide materials.
PMID- 28513477
TI - Microtube array membrane bioreactor promotes neuronal differentiation and
orientation.
AB - An important challenge in neuronal tissue engineering is to create innovative
tools capable of promoting cellular response in terms of neuronal differentiation
and neurite orientation that may be used as investigational platforms for
studying neurobiological events and neurodegenerative disorders. A novel membrane
bioreactor was created to provide a 3D well-controlled microenvironment for
neuronal outgrowth. The bioreactor consisted of poly-L-lactic acid highly aligned
microtube array (PLLA-MTA) membranes assembled in parallel within a chamber that
establish an intraluminal and an extraluminal compartment whose communication
occurs through the pores of the MTA membrane walls. The bioreactor configuration
provided a wide surface area for cell adhesion in a small volume, and offered a
peculiar arrangement that directed neuronal orientation. The combination of an
appropriate membrane porosity, pore interconnectivity and very thin walls ensured
optimal indirect perfusion to cell compartment, and enhanced the mass transfer of
metabolites and catabolites protecting neurons from shear stress. The PLLA-MTA
membrane bioreactor promoted the growth and differentiation of SH-SY5Y cells
toward a neuronal phenotype, and guided neurite alignment giving rise to a 3D
neuronal tissue-like construct. It provides an innovative platform to study
neurobiological phenomena in vitro and by guiding neuronal orientation for repair
and/or regeneration.
PMID- 28513478
TI - A gaze independent hybrid-BCI based on visual spatial attention.
AB - OBJECTIVE: Brain-computer interfaces (BCI) use measures of brain activity to
convey a user's intent without the need for muscle movement. Hybrid designs,
which use multiple measures of brain activity, have been shown to increase the
accuracy of BCIs, including those based on EEG signals reflecting covert
attention. Our study examined whether incorporating a measure of the P3 response
improved the performance of a previously reported attention-based BCI design that
incorporates measures of steady-state visual evoked potentials (SSVEP) and alpha
band modulations. APPROACH: Subjects viewed stimuli consisting of two bi
laterally located flashing white boxes on a black background. Streams of letters
were presented sequentially within the boxes, in random order. Subjects were cued
to attend to one of the boxes without moving their eyes, and they were tasked
with counting the number of target-letters that appeared within. P3 components
evoked by target appearance, SSVEPs evoked by the flashing boxes, and power in
the alpha band are modulated by covert attention, and the modulations can be used
to classify trials as left-attended or right-attended. MAIN RESULTS: We showed
that classification accuracy was improved by including a P3 feature along with
the SSVEP and alpha features (the inclusion of a P3 feature lead to a 9% increase
in accuracy compared to the use of SSVEP and Alpha features alone). We also
showed that the design improves the robustness of BCI performance to individual
subject differences. SIGNIFICANCE: These results demonstrate that incorporating
multiple neurophysiological indices of covert attention can improve performance
in a gaze-independent BCI.
PMID- 28513479
TI - Producing lasting amphiphobic building surfaces with self-cleaning properties.
AB - Nowadays, producing building surfaces that prevent water and oil uptake and which
present self-cleaning activity is still a challenge. In this study, amphiphobic
(superhydrophobic and oleophobic) building surfaces were successfully produced. A
simple and low-cost process was developed, which is applicable to large-scale
building surfaces, according the following procedure: (1) by spraying a SiO2
nanocomposite which produces a closely-packed nanoparticle uniform topography;
(2) by functionalizing the previous coating with a fluorinated alkoxysilane,
producing high hydrophobicity and oleophobicity. The formation of a Cassie-Baxter
regime, in which air pockets could be trapped between the aggregates of
particles, was confirmed by topographic study. The building surface demonstrated
an excellent self-cleaning performance. Finally, the surface presented lasting
superhydrophobicity with high stability against successive attachment/detachment
force cycles. This high durability can be explained by the effective grafting of
the silica nanocomposite coating skeleton with the substrate, and with the
additional fluorinated coating produced by condensation reactions.
PMID- 28513480
TI - Highly sensitive and scalable AAO-based nano-fibre SERS substrate for sensing
application.
AB - Well-ordered periodic nanostructures are excellent substrates for many surface
enhanced Raman spectroscopy (SERS) applications. Conventional fabrication
approaches such as high precision electron beam lithography or focused ion beam
produce high resolution nano-features with great reproducibility at the expense
of low throughput. In this work, a highly sensitive and scalable AAO-nano-fibre
(ANF) SERS substrate is demonstrated by optimising the second anodisation time of
the standard two-step anodisation of aluminium and performing an additional wet
etching step on the resulting AAO substrate. The optimised ANF substrate exhibits
SERS sensitivity that surpasses the AAO nanoholes and the metal-film-on
nanoparticles substrates. A detection limit of 0.1 nM is achieved with a signal
to-noise ratio of 2.6-3 using a low excitation power of 0.1 mW. The ANF substrate
exhibits an enhancement factor of 9.28 * 106 and a standard deviation of no more
than 8%. The results indicate that the highly sensitive and scalable ANF
substrate is a promising substrate for commercial SERS application.
PMID- 28513481
TI - Recurrent painful lesions on the lower lip.
PMID- 28513482
TI - Trichosporon inkin causing subcutaneous sinus tract: Successfully treated by oral
and ultrasound-guided intralesional itraconazole therapy.
PMID- 28513484
TI - Bilateral subungual epidermoid inclusions of big toes.
PMID- 28513483
TI - A case of dermatomyositis with underlying unusual malignancy.
PMID- 28513485
TI - Acantholysis or the Auspitz sign? A revelation of the life of Carl Heinrich
Auspitz.
PMID- 28513486
TI - Pegylated liposomal doxorubicin-induced miliaria crystallina and lichenoid
follicular eruption.
PMID- 28513487
TI - Every ending is a new beginning.
PMID- 28513488
TI - Imaging in tuberculosis-associated uveitis.
AB - Intraocular tuberculosis (TB) can have several clinical presentations, affecting
nearly every tissue of the eye. These clinical signs have specific imaging
characteristics which help in associating them with tuberculous etiology. This
review enumerates the conventional and emerging imaging techniques for
intraocular TB and highlights their clinical application for diagnosis and
management of specific clinical presentations.
PMID- 28513489
TI - The influence of corneal collagen cross-linking on anterior chamber in
keratoconus.
AB - AIMS: This study aimed to evaluate the effect of the corneal changes following
corneal cross-linking (CXL) on the anterior chamber in keratoconus patients.
MATERIALS AND METHODS: Forty-five eyes of 32 patients who had been diagnosed with
progressive keratoconus and had undergone CXL were included in this retrospective
study. The thinnest corneal thickness of the progressive keratoconus patients
included in the study was >400 MU. The preoperative (T0), postoperative 6th month
(T1), and postoperative 1st year (T2) anterior chamber volume (ACV), anterior
chamber angle (ACA), and anterior chamber depth (ACD) scheimpflug imaging values
were obtained for each eye. RESULTS: The mean T0 ACV value was 182.79 +/- 36.68
mmwhile the T1 value was 201.25 +/- 41.73 mm3 and the T2 value was 208.40 +/-
42.69 mm3 with a statistically significant difference between the periods (P =
0.001). The mean T0 ACA value was 38.64 degrees +/-5.85 degrees , increasing to
41.45 degrees +/-4.83 degrees in the T1 and 42.10 degrees +/- 4.84 degrees in
the T2. The T0 value was significantly lower than the post-CXL values (P =
0.003). The mean ACD value was 3.73 +/- 0.29 mm at the T0 and 3.82 +/- 0.38 mm at
the T1 and 3.84 +/- 0.36 mm at the T2. The pre-CXL values were significantly
lower than the post-CXL values (P = 0.001). CONCLUSIONS: The improvement of
corneal parameters by CXL in keratoconus patients can have a positive effect on
anterior chamber parameters as well. This effect becomes marked at the
postoperative first 6-month evaluation.
PMID- 28513490
TI - Coexistence of herpes simplex virus infection in microsporidial stromal keratitis
associated with granulomatous inflammation.
AB - BACKGROUND: Microsporidial stromal keratitis poses several diagnostic challenges.
Patients may present with corneal ulceration, marked stromal thinning, or even as
a quite corneal scar. The presentation of microsporidial stromal keratitis
commonly mimics viral keratitis. Microbiology scrapings are usually helpful;
however, scraping and culture-negative cases pose a significant diagnostic
dilemma. Histopathological examination is diagnostic but shows varying degree of
inflammation, predominantly composed of polymorphonuclear leukocytes.
Granulomatous inflammation, in microsporidial stromal keratitis, is never well
described, and the authors in this article aim to describe the presence of
granulomatous inflammation in microsporidial stromal keratitis, in patients with
associated herpes simplex virus (HSV) keratitis. METHODS: This was a
retrospective and observational study conducted at a tertiary eye care center.
RESULTS: Of 263 patients who underwent therapeutic penetrating keratoplasty for
infectious keratitis, during 2011-2013, seven patients were diagnosed as
microsporidial stromal keratitis. Microsporidial spores could be demonstrated on
microbiological scrapings in 5/7 (71%) of cases, but identified on
histopathological examination and also confirmed on polymerase chain reaction
(PCR) for microsporidium in 100% of cases. There was evidence of diffuse stromal
necrosis with markedly severe degree of polymorphonuclear leukocytic infiltrates,
with granulomatous inflammation in 42% of cases. Interestingly, these were
positive for HSV-1 DNA on PCR. Review of medical records revealed much severe
clinical presentations in patients with granulomatous inflammation, in comparison
to cases without granulomatous inflammation. CONCLUSIONS: The authors hereby
recommend that severe clinical presentation in patients with microsporidial
stromal keratitis, markedly dense polymorphonuclear leukocytic infiltrates or the
presence of granulomatous inflammation on the histopathological examination,
should be investigated further for the presence of HSV-1 DNA for better patient
management and good visual outcome.
PMID- 28513491
TI - Results of a new "mirror tuck technique" for fixation of lacrimal bypass tube in
conjunctivodacryocystorhinostomy.
AB - CONTEXT: Conjunctivodacryocystorhinostomy (CDCR) is the procedure of choice for
proximal canalicular blocks. However, the complications of tube migration and
extrusion limit its widespread practice. AIM: The aim of this study is to
evaluate the efficacy and complications of the new "mirror tuck technique" for
fixation of lacrimal bypass glass tube without holes in proximal canalicular
blocks in laser CDCR. MATERIALS AND METHODS: A prospective interventional study
was conducted in forty consecutive eyes of adult patients, undergoing 980 nm
diode laser CDCR for proximal canalicular blocks. After creating the tract under
endoscopic guidance, the collar of the glass tube was fixed to the conjunctiva
with 6-0 prolene suture by "mirror tuck technique." Success was defined as the
absence of extrusion of tube with patent tract and relief in epiphora at 1 year
of follow-up. RESULTS: Both anatomical and functional success was achieved in 39
(97.5%) cases. Tube displacement occurred in one patient suffering from allergic
conjunctivitis in which the tube had to be removed. A temporary heaviness was
reported by 5 (12.5%) patients till about 2 weeks. Conjunctival overgrowth over
the tube occurred in 1 (2.5%) eye at 5 months which was excised and treated with
application of 0.02% mitomycin C with no subsequent recurrence. There were no
cases of suture abscess or suture intolerance warranting tube removal.
CONCLUSION: "Mirror tuck technique" is an effective method for tube fixation (for
tube without holes) in CDCR. However, it is important to position the
conjunctival opening so as to leave sufficient space for passage of sutures for
anchorage medially.
PMID- 28513492
TI - Repeatability and agreement of five imaging systems for measuring anterior
segment parameters in healthy eyes.
AB - PURPOSE: The purpose of this study is to assess the repeatability and agreement
of five imaging devices, namely, the Pentacam (Oculus), Sirius (CSO), Orbscan IIz
(Bausch and Lomb), Corvis (Oculus), and ultrasound pachymetry (UP, Tomey) in
measuring steep keratometry (sKm), flat keratometry (fKm), central corneal
thickness (CCT), thinnest corneal thickness (TCT), and anterior chamber depth
(ACD) in healthy individuals. DESIGN: This was prospective, comparative study.
SUBJECTS: Forty-six healthy Indian patients. MATERIALS AND METHODS: Forty-six
eyes of 46 healthy participants underwent three consecutive scans on each device
by a single examiner. Within-subject standard deviation, test-retest
repeatability (TRT), and coefficient of variation (COV) for assessing
repeatability and Bland-Altman plots for the agreement between the mean
measurements of each machine were analyzed. MAIN OUTCOME MEASURES: The
repeatability and agreement between the five devices for the measurements of sKm,
fKm, CCT, TCT, and ACD. RESULTS: The TRT of sKm measurements ranged between 0.23
diopter (D) (with Pentacam) and 0.83 D (with Orbscan). The same of fKm, TCT, ACD,
and CCT measurements ranged between 0.28 D (with Pentacam) and 0.74 D (with
Sirius), 7.78 MUm (Sirius) and 19.81 MUm (Orbscan), 0.05 mm (Orbscan) and 0.07
(Sirius), and 7.36 MUm (Sirius) and 18.02 MUm (Orbscan), respectively. The TRT of
sKm and fKm measurements with Pentacam was significantly lower than those with
Orbscan and Sirius. The TRT of TCT measurement with Sirius was significantly
lower than that with Pentacam (4.53 MUm) and Orbscan (7.15 MUm). There were
statistically significant differences in the mean measurements of all parameters
between the devices. The 95% limit of agreement on the Bland-Altman analysis was
wide for the measurement pairs with all the devices. Significant proportional
bias in the agreement was detected for TCT measurements with all the device pairs
and for the ACD measurements between Sirius and Pentacam. CONCLUSIONS: The
repeatability estimates of sKm, fKm, TCT, ACD, and CCT measurements with
Pentacam, Orbscan, Sirius, Corvis, and UP in Indian eyes were good. However, the
differences in the measurements between the devices were statistically
significant and the same cannot be used interchangeably for anterior segments
measurements.
PMID- 28513493
TI - Inflammatory choroidal neovascularization in Indian eyes: Etiology, clinical
features, and outcomes to anti-vascular endothelial growth factor.
AB - BACKGROUND AND OBJECTIVES: The aim was to study the clinical profile of
inflammatory choroidal neovascularization (CNV) and its treatment response to
intravitreal bevacizumab or ranibizumab on pro re nata (PRN) basis in Indian
eyes. MATERIALS AND METHODS: This was a retrospective case series of consecutive
patients with inflammatory CNV treated with anti-vascular endothelial growth
factor (anti-VEGF) in a tertiary eye care center in Eastern India between 2009
and 2014. The data about clinical features, investigations, treatment, and
outcomes were obtained from the medical records. We included patients with active
inflammatory CNV but with no evidence of inflammation and were treated with anti
VEGF alone, with a minimum follow-up of 6 months. Main outcome measures were a
clinical and etiological profile of inflammatory CNV in Indian eyes and their
response to treatment. RESULTS: Thirty eyes of 28 patients were included in the
study. The mean follow-up was 17.93 +/- 14.28 months (range 6-53 months). In our
cohort, seven (23.33%) eyes had inflammatory CNV secondary to idiopathic
choroiditis, four (13.33%) eyes had toxoplasmosis, idiopathic panuveitis, and
Vogt Koyanaki Harada's disease each. Three (10%) eyes had geographic helicoid
peripapillary choroidopathy and tubercular choroiditis each. Remaining two
(6.66%) eyes had punctate inner choroidopathy, while multifocal choroiditis with
panuveitis, resolved endogenous endophthalmitis and Hansen's diseases were the
etiology in one (3.33%) case of inflammatory CNV each. The mean number of
injections were 2.76 (range 1-5). Among thirty eyes of inflammatory CNV, 16
(53.3%) eyes showed improvement, eight (26.6%) maintained the same vision,
whereas six (20%) eyes showed deterioration of vision. Interpretations and
Conclusion: Idiopathic choroiditis was the most common cause of inflammatory CNV
and PRN intravitreal anti-VEGF (ranibizumab or bevacizumab) appears to have
effective treatment response.
PMID- 28513494
TI - Tear film and ocular surface dysfunction in diabetes mellitus in an Indian
population.
AB - PURPOSE: Ophthalmic complications in diabetes such as retinopathy, cataract, and
infections have been extensively studied. Recently, attention has been drawn
toward ocular surface changes in diabetes mellitus (DM). This study has been
carried out to investigate the tear film and ocular surface abnormalities in type
II DM patients. MATERIALS AND METHODS: A total of 83 participants (130 eyes) were
enrolled: 53 diabetics (80 eyes) and 30 healthy controls (50 eyes). Of the 53
diabetics, 24 patients (42 eyes) had some diabetic retinopathy. The tear film and
ocular surface were evaluated using Schirmer test, tear film break-up time
(TBUT), keratoepitheliopathy score (KES), Rose Bengal Staining (RBS) test, and
conjunctival impression cytology. RESULTS: When compared with the healthy
controls, diabetics showed significantly reduced Schirmer, TBUT measurements and
the higher grades of KES and RBS test (P < 0.001). Impression cytology analysis
showed goblet cell loss and conjunctival squamous metaplasia in diabetics.
CONCLUSION: Tear film abnormality is a significant feature of diabetic ocular
surface diseases. These abnormalities are likely on account of poor quality and
function of tears, combined with the subnormal ocular surface. Therefore, all
diabetic patients especially those with evidence of retinopathy changes should
undergo routine early examination and follow-up of tear function and ocular
surface parameters.
PMID- 28513495
TI - Effect of post crosslinking haze on the repeatability of Scheimpflug-based and
slit-scanning imaging devices.
AB - PURPOSE: The aim of this study was to analyze the effect of postcollagen
crosslinking (CXL) haze on the measurement and repeatability of pachymetry and
mean keratometry (Km) of four corneal topographers. MATERIALS AND METHODS: Sixty
eyes of sixty patients with progressive keratoconus who had undergone accelerated
CXL (ACXL) underwent imaging with a scanning slit imaging device (Orbscan II) and
three Scheimpflug imaging devices (Pentacam HR, Sirius, and Galilei). Post-ACXL
haze was measured using the densitometry software on the Pentacam HR. Readings of
the thinnest corneal thickness (TCT) and Km from three scans of each device were
analyzed. Effect of haze on the repeatability of TCT and Km measurements was
evaluated using regression models. Repeatability was assessed by coefficient of
variation. RESULTS: Corneal densitometry in different zones affected the
repeatability of TCT measurement of Orbscan (P < 0.05) significantly but not the
repeatability of TCT with Pentacam HR and Sirius (P = 0.03 and 0.05,
respectively). Km values were affected by haze when measured with the Pentacam HR
(P < 0.05). The repeatability of Km readings for all devices was unaffected by
haze. In the anterior 0-2 mm and 2-6 mm zone, TCT (P = 0.43 and 0.45,
respectively), Km values (P = 0.4 and 0.6, respectively), repeatability of TCT (P
= 0.1 in both zones), and Km (P = 0.5 and 0.1, respectively) with Galilei were
found to be the most reliable. CONCLUSION: Galilei measurements appear to be
least affected by post-ACXL haze when compared with other devices. Hence,
topography measurements in the presence of haze need to be interpreted with
caution.
PMID- 28513496
TI - Intra-arterial chemotherapy for retinoblastoma: Two-year results from tertiary
eye-care center in India.
AB - AIM: The aim of this study is to describe treatment outcomes and complications of
selective intra-arterial chemotherapy (IAC) for intraocular retinoblastoma (RB).
MATERIALS AND METHODS: A retrospective, interventional series of 10 eyes with RB
which underwent IAC using melphalan (5 mg/7.5 mg) and topotecan (1 mg), or
melphalan (5 mg/7.5 mg) alone. Treatment outcomes were evaluated in terms of
tumor control, vitreous seeds (VS) and subretinal seeds (SRS) control, and globe
salvage rates. RESULTS: Ten eyes of 10 patients underwent 38 IAC sessions (mean =
3.8; median = 4; range = 3-5 sessions). Following IAC, complete regression of
main tumor was seen in 9 eyes (90%) and partial regression in 1 (10%). All four
eyes with SRS showed complete regression (100%). Of 5 eyes with VS, 3 eyes (60%)
showed complete regression, 1 eye (20%) showed relapse, while 1 eye (20%) showed
no response. Globe salvage was achieved in 8 of 10 eyes (80%). Complications
included transient ophthalmic artery narrowing (n = 2), branched retinal vein
occlusion (n = 1), forehead skin pigmentation (n = 1), and vitreous hemorrhage (n
= 2). There was no case of stroke, hemiplegia, metastasis, or death. Transient
hematological changes included relative pancytopenia (n = 4), relative leukopenia
(n = 5), and relative thrombocytopenia (n = 4). Mean follow-up was 26 months
(median = 28, range = 13-36) from the initiation of first IAC. CONCLUSIONS: IAC
is an effective therapy for globe preservation in eyes with intraocular RB, in
the setting of a developing country like India. Larger studies with longer follow
up are required to validate these results.
PMID- 28513497
TI - Sialadenitis following blepharoplasty: An unusual sequelae.
PMID- 28513498
TI - Combination of phototherapeutic keratectomy and wavefront-guided photorefractive
keratectomy for the treatment of Thiel-Behnke corneal dystrophy.
AB - Phototherapeutic keratectomy (PTK) has been used to treat anterior corneal
dystrophy but may cause hyperopic shift or corneal high-order aberration. We
describe the successful treatment of a case of a 43-year-old female with Thiel
Behnke corneal dystrophy, using PTK followed by wavefront-guided photorefractive
keratectomy (PRK). The patient had high corneal aberration and hyperopic shift
after PTK in both eyes. The corneal surface regularity index and surface
asymmetric index increased after PTK and decreased after wavefront-guided PRK.
Vision improved from preoperative 20/400 and 20/60 to postoperative 20/20 and
20/25 in the right eye and the left eye, respectively. Additional wavefront
guided PRK may enhance the effects of PTK by reducing irregular corneal surfaces
and by correcting PTK-induced hyperopic shift.
PMID- 28513499
TI - Role of mini-scleral lens in mucous membrane pemphigoid.
AB - This study aims to report the use of mini-scleral contact lens in the management
of mucous membrane pemphigoid (MMP) with persistent epithelial defects. A 68-year
old male with a history of ocular pain and declining visual acuity was referred
to our clinic with a diagnosis of MMP. His corrected distance visual acuity
(CDVA) was 20/200 in the right eye and 20/100 in the left eye. Despite being on
lubricants, topical steroids and intravenous cyclophosphamide, the patient
developed persistent corneal epithelial defects in both eyes. He was then given a
trial of mini-scleral lenses. Within 4 weeks, corneal epithelial defects healed,
and at 6 months, the CDVA had improved to 20/50 in the right eye and 20/40 in the
left eye. By improving the corneal surface integrity and visual function, mini
scleral lenses can play a role in the visual rehabilitation of patients with MMP.
PMID- 28513500
TI - Rescue vitrectomy with blocked artery massage and bloodletting for branch retinal
artery occlusion.
AB - A 61-year-old male suffered from sudden blurred vision and superior visual field
defect oculus dexter. His vision was counting fingers at 20 cm. Fundoscopy
demonstrated inferior pale retina and a large embolus located at the proximal
inferior retinal artery. Branch retinal artery occlusion (BRAO) was diagnosed.
Initial paracentesis, topical brimonidine tartrate, oral pentoxifylline, and
hyperbaric oxygen therapy were performed but showed limited improvement. Hence,
he received 25-gauge vitrectomy, artificial posterior vitreous detachment,
blocked retinal artery massage, and bloodletting 5 days after onset. After the
surgery, his vision improved to 20/25. Fundoscopy showed reperfused retina, and
optical coherence tomography revealed resolved retinal edema. RAO is an
ophthalmological emergency; however, no standard guideline is available.
Vitrectomy with blocked retinal artery massage and bloodletting showed favorable
results in this case of BRAO with a large embolus. More prospective clinical
trials are needed for setting up the standard treatment.
PMID- 28513501
TI - Ocular surface burn secondary to smart phone battery blast.
PMID- 28513502
TI - Comment on: To assess survival outcomes of combined femtosecond laser-assisted
cataract surgery with 25-gauge vitrectomy surgery at a tertiary eye care center.
PMID- 28513503
TI - Authors' reply.
PMID- 28513504
TI - Fundus findings in a case of Joubert syndrome.
PMID- 28513505
TI - Practice of trabeculectomy by ophthalmologists in Nigeria.
AB - AIM: To assess the practice of trabeculectomy among ophthalmologists in Nigeria.
MATERIALS AND METHODS: This was a cross-sectional study in which structured, self
administered questionnaires were distributed to 80 consenting ophthalmologists
present during the 2010 annual scientific session of the Ophthalmological Society
of Nigeria. All consenting ophthalmologists treat glaucoma patients. Information
obtained were demographic characteristics, glaucoma outpatient load, number of
trabeculectomies performed in the preceding 1 year and during residency training,
and factors influencing trabeculectomy practice. Data were analyzed with
Statistical Package for Social Science version 16.0. Relationships between
variables were tested using the *2 test for statistical significance. RESULTS:
Sixty-five of the 80 consenting ophthalmologists responded to the questionnaires
(81.3% response rate); 32 (53.3%) were females and 28 (46.7%) were males (5 non
responders). Ages ranged from 30 to 60 years with a mean of 44 years +/- SD 7.7.
Only 36 (57.1%) performed trabeculectomy in the 1 year preceding the study. There
was an overall trabeculectomy rate of 0.9/ophthalmologist/month. Of the 15
respondents who performed more than 15 trabeculectomies during residency, 14
(93.3%) also performed the surgery in the year preceding this study (P = 0.001).
The main limitation to the practice of the procedure was patients' unwillingness
to accept surgery, as identified by 50 (89.3%) respondents. CONCLUSIONS: A low
trabeculectomy rate of 0.9/ophthalmologist/month was found in this study. It was
significantly associated with insufficient exposure to the surgery during
residency training and patients' poor acceptance of the surgery.
PMID- 28513506
TI - Surgical difficulties, success, and complication rates of orthodontic miniplate
anchorage systems: Experience with 382 miniplates.
AB - PURPOSE: The aim of this study was to evaluate the complications and success
rates of the miniplates using both maxilla and mandible for orthodontic anchorage
in growing patients. MATERIALS AND METHODS: One hundred and fifty-five
consecutive patients (range 8.7-13.8 years) with Class II and III malocclusion
without congenital or acquired deformities were included in this study. A total
of 382 titanium miniplates were placed by the same surgeon. All miniplates were
inserted under local anesthesia. Loading of the miniplates with a force of 200 g
with the help of elastics or functional devices were initiated 3 weeks after
surgery. RESULTS: The overall success rate of miniplate anchorage in terms of
stability was 96.8%. Twenty-one patients reported irritation of the mucosa of the
cheeks or lower lip after the surgery in the mandible group. Twelve miniplates
needed to be removed and were successfully replaced. CONCLUSION: Skeletal
anchorage miniplates is effective for correcting malocclusions. Success depends
on proper presurgical patient counseling, minimally invasive surgery, good
postsurgical instructions, and orthodontic follow-up.
PMID- 28513507
TI - Early pregnancy plasminogen activator inhibitor-1 levels in Nigerian women and
its relationship with preeclampsia.
AB - AIM: This study compared early plasma levels of plasminogen activator inhibitor-1
(PAI-1) in normal pregnancy and preeclampsia and determined its relationship with
disease severity. SUBJECTS AND METHODS: This was a prospective cohort study of
195 normotensive, aproteinuric pregnant women without prior history of
gestational hypertension. The women were attending the Antenatal Clinic at The
Lagos University Teaching Hospital and were within 24 weeks gestation at
recruitment. The outcome measures were PAI-1, systolic blood pressure (SBP),
diastolic blood pressure (DBP), and significant proteinuria. The endpoint of the
study was the development of preeclampsia. The diagnosis of preeclampsia was made
by the attending Obstetrician. The data were analyzed using the IBM SPSS
statistical software. Statistical significance was set at P < 0.05. RESULTS:
First trimester PAI-1 levels were significantly higher in the women who later
developed preeclampsia compared to those who had a normal pregnancy (P < 0.0001).
In these group of women who later developed preeclampsia, PAI-1 had an inverse
relationship with gestational age (r = 0.878) whereas in normal pregnancy, PAI-1
and gestational age had a direct relationship (r = 0.017). Second trimester
systolic and DBP values were also significantly higher in the women who later
developed preeclampsia compared to normal pregnancy, P = 0.007 and 0.004,
respectively. There was, however, no correlation between PAI-1 values and SBP,
DBP and proteinuria in the women who developed preeclampsia. CONCLUSION: Plasma
levels of PAI-1 are increased early in pregnancies complicated by preeclampsia,
but the lack of correlation of this marker with disease severity may limit its
clinical utility.
PMID- 28513508
TI - Harmful effects of formaldehyde and possible protective effect of Nigella sativa
on the trachea of rats.
AB - OBJECTIVE: We aimed in this study to investigate the harmful effects of
formaldehyde (FA) inhalation and possible protective effects of Nigella sativa
(NS) on rats' trachea. MATERIALS AND METHODS: In this study, 63 adult male rats
were used. Animals were divided into nine groups. Group I was used as control
group. All other groups were exposed to FA inhalation. Group III, V, VII, and IX
were administered NS by gavage. Tissues were examined histologically, and
immunohistochemical examination for Bax and caspase-3 immunoreactivity was
carried out. RESULTS: Our study demonstrated that FA caused apoptosis in the
tracheal epithelial cells. The most apoptotic activity occurred at a 10 ppm dose
in a 13-week exposure. Distortion of tracheal epithelium and cilia loss on
epithelial surface was present in all groups. However, NS treated Groups VII and
IX had decreased apoptotic activity and lymphoid infiltration and protected the
epithelial structure, despite some shedded areas. Difference of tracheal
epithelial thickness and histological score was statistically significant between
Group VI-VII and VIII-IX. CONCLUSION: FA induces apoptosis and tracheal
epithelial damage in rats, and chronic administration of NS can be used to
prevent FA-induced apoptosis and epithelial damage.
PMID- 28513509
TI - Relationship between alexithymia and chronic periodontitis.
AB - OBJECTIVE: The aim of this study was to investigate the potential relationship
between alexithymia and chronic periodontitis. MATERIALS AND METHODS: A case
control study of 222 male and female subjects aged 21-63 years was conducted. The
participants were divided into a chronic periodontitis group (n = 114) and a
control group (n = 108) with no history of periodontitis. The Toronto Alexithymia
Scale (TAS-20) was used to evaluate alexithymia status of the subjects. Clinical
data were collected on parameters such as the plaque index, bleeding on probing,
probing depth, and the clinical attachment level (CAL). Socioeconomic data on the
patients were also recorded. RESULTS: Chronic periodontitis group showed higher
frequency in alexithymic patients as compared to control group. The proportion of
high dental anxiety did not differ between the groups. The total TAS-20 score was
statistically significantly higher in male subjects than in female subjects (P <
0.05). The bivariate analyses of the psychometric measures and the periodontal
parameters revealed positive correlations with the severity of periodontal
disease/CAL and the total TAS-20 score (P < 0.05). CONCLUSION: The results of the
current study suggest that alexithymia is a possible risk factor for chronic
periodontitis. Further research is needed to identify the underlying mechanism.
PMID- 28513510
TI - Factors associated with blood pressure control in predialysis chronic kidney
disease patients: Short-term experience from a single center in Southern Nigeria.
AB - BACKGROUND: Hypertension is a leading cause of kidney disease worldwide, and
chronic kidney disease (CKD) is a known cause of secondary hypertension. Blood
pressure (BP) control is a main-stay in the management of CKD because it retards
the progression of established CKD. AIM: To determine BP control and its
associated factors in predialysis CKD patients in a tertiary hospital setting.
METHODOLOGY: CKD patients who attended the renal outpatient clinic during the
period from December 2013 to June 2014 were recruited into the study. Demographic
and clinical information were obtained from their case records. The average of
the three most recent clinic BPs was calculated for each patient. Good BP control
was taken as an average BP of <140/90 mmHg. RESULTS: One hundred and three
patients (53 males and 50 females) met inclusion criteria for the study. The mean
age of the patients was 40.6 +/- 17.4 years. Estimated glomerular filtration rate
was <60 ml/min in 49.5% of patients. Good BP control was seen in 57 (55.3%)
patients. Poor BP control was associated with middle age, proteinuric CKD, and
prescription of 3 or more BP medication. CONCLUSION: BP control in predialysis
CKD patients still needs to be optimized. Special attention should be given to
middle-aged patients who have proteinuric CKD and those on multiple BP drugs
without optimal BP control.
PMID- 28513511
TI - Comparison of elasticity values of the right lobe of the liver of normal weight
and morbidly obese Turkish patients.
AB - INTRODUCTION: Shear wave elastography is a method for the measurement of tissue
stiffness. The advantage of this method is that its outcome is not operator
dependent. Our aim was to compare the elastiscity values of the right lobe of the
liver of normal weighted and morbidly obese patients. MATERIALS AND METHODS: The
mean elastiscity values of the right lobe of the liver were calculated for 38
normal weighted and 37 morbidly obese patients. All the patients had no history
of liver disease. RESULTS: The mean elastiscity value was significantly higher in
morbidly obese patients than (25,7 +3,30 kPascal) in normal weighted patients for
the right lobe of liver (10,55 +2,20 kPascal). CONCLUSION: Morbidly obese
patients have a potential risk for liver fibrosis even in the absence of
hepatosteatosis.
PMID- 28513512
TI - Effects of laser etching on shear bond strengths of brackets bonded to fluorosed
enamel.
AB - AIM: To evaluate the effects of laser etching on the shear bond strengths (SBS)
and failure modes of brackets bonded to fluorosed enamel. MATERIALS AND METHODS:
This in vitro study included 34 fluorosed and 34 nonfluorosed teeth. Teeth were
divided into four subgroups according to the etching procedure: Group (A) normal
enamel etched with 37% phosphoric acid for 15 s, Group (B) nonfluorosed enamel
etched with erbium:yttrium aluminum garnet (Er: YAG) laser for 15 s, Group (C)
fluorosed enamel etched with 37% phosphoric acid for 30 s, Group (D) fluorosed
enamel etched with Er: YAG laser for 30 s. After bonding of the premolar metal
brackets, specimens were subjected to the thermal cycles. After SBS test,
modified adhesive remnant index (ARI) by using stereomicroscope and failure modes
with a scanning electron microscope (SEM) was determined. After bonding, one
specimen from each group was examined under SEM to identify enamel-resin
interfaces. ANOVA and Tukey post-hoc tests were used to compare the SBS values.
The Kruskal-Wallis and Chi-square tests were used to analyze the distribution of
ARI scores and failure modes of groups. RESULTS: The highest mean SBS value
(17.56 +/- 1.05 MPa) was found in Group A, while the lowest (12.25 +/- 0.96 MPa)
in Group D. Significant differences were found in the SBS test and failure modes
among all groups. The differences between ARI scores of the groups were not
significant. CONCLUSION: According to our findings, laser etching reduced the SBS
of brackets bonded to fluorosed teeth, but provided clinically acceptable SBS
values.
PMID- 28513513
TI - Electrocardiographic changes and troponin T levels in children with severe
malaria anemia and heart failure.
AB - BACKGROUND: Severe malaria anemia is a major cause of childhood heart failure in
malaria endemic countries. The resulting hypoxic-ischemic injuries may cause
myocardial damage detectable by electrocardiogram (ECG) and elevated troponin T
(cTnT) levels. OBJECTIVE: Evaluate the ECG changes and cTnT levels in children
with severe malaria anemia compared with those who had uncomplicated malaria
without anemia. METHODS: Consecutive children with severe malaria anemia were
recruited as subjects while controls were age- and gender-matched children with
uncomplicated malaria without anemia. ECG findings, cTnT levels, and the
proportion of children with elevated cTnT were compared between subjects and
controls. RESULTS: There were 43 subjects with a mean age of 25.7 +/- 22.9
months. Controls were forty children; mean age was 31.2 +/- 20.0 months. All the
subjects and 10 (25.0%) controls had ECG abnormalities. Five (11.6%) subjects and
no control had ST segment changes, P = 0.06. Twenty-three percent of subjects
compared to 5% of the controls had prolonged QTc, P = 0.027. Median cTnT of
subjects (131.8 ng/L) was not significantly higher than the 85.9 ng/L of
controls, P = 0.99. The median cTnT of subjects that died 208.9 ng/L was higher
than in survivors 99.6 ng/L, P = 0.51. CONCLUSION: Prolonged QTc was more
prevalent in children with severe malaria anemia compared to those without
anemia, suggesting that children with severe malaria anemia were more prone to
arrhythmias. The median cTnT value in the subjects was not significantly lower
than that in controls, suggesting that children with severe malaria anemia are
not prone to myocardial injury any more than those with uncomplicated malaria
without anemia.
PMID- 28513514
TI - Efficacy of polishing kits on the surface roughness and color stability of
different composite resins.
AB - OBJECTIVE: Different polishing kits may have different effects on the composite
resin surfaces. The aim of this study was to evaluate the surface roughness and
color stability of four different composites which was applied different
polishing technique. MATERIALS AND METHODS: Thirty specimens were made for each
composite resin group (nanohybrid, GrandioSo-GS; nanohybrid, Clearfil Majesty
Esthetic-CME; hybrid, Valux Plus-VP; micro-hybrid, Ruby Comp-RC; [15 mm in
diameter and 2 mm height]), with the different monomer composition and particle
size from a total of 120 specimens. Each composite group was divided into three
subgroups (n = 10). The first subgroup of the each composite subgroups served as
control (C) and had no surface treatment. The second subgroup of the each
composite resin groups was polished with finishing discs (Bisco Finishing Discs;
Bisco Inc., Schaumburg, IL, USA). The third subgroup of the each composite resin
was polished with polishing wheel (Enhance and PoGo, Dentsply, Konstanz,
Germany). The surface roughness and the color differences measurement of the
specimens were made and recorded. The data were compared using Kruskal-Wallis
test, and regression analysis was used in order to examine the correlation
between surface roughness and color differences of the specimens (alpha = 0.05).
RESULTS: The Kruskal-Wallis test indicated significant difference among the
composite resins in terms of DeltaE (P < 0.05), and there was no statistically
significant difference among composite resins in terms of surface roughness (P >
0.05). Result of the regression analysis indicated statistically significant
correlation between Ra and DeltaE values (P < 0.05, r2 = 0.74). CONCLUSION: The
findings of the present study have clinical relevance in the choice of polishing
kits used.
PMID- 28513515
TI - Relationship between knowledge and quality of asthma care among physicians in
South-West Nigeria.
AB - INTRODUCTION: Adequate knowledge of asthma management and adherence to
international guidelines are known to increase the quality of care offered by
Physicians. We conducted this study to assess the level of asthma knowledge and
quality of care among physicians practicing in Ondo State. METHODS: We conducted
a cross sectional survey of 96 physicians from various specialties participating
in a continuous professional development (CPD) lecture using adapted
questionnaires. RESULT: Respondents ranged in age from 23-62years (42.5+/-19.4).
There were more male (70%). The minority (17%) had additional postgraduate
medical qualifications. There was a high distribution of correct answers for
individual knowledge questions. The greatest areas of knowledge gaps appeared in
diagnostic instruments, asthma severity and drugs. We observed gaps regarding the
use of GINA guidelines (6%) and prescribing combined inhaled steroid and long
acting bronchodilator for patients who are not controlled on inhaled steroid
alone (29%). A large number of the respondents do not confirm the diagnosis of
asthma by spirometry (32%). Only 8% of the respondents with high knowledge
reported a corresponding high quality of Asthma care. CONCLUSION: We concluded
that although physicians in South-West Nigeria appear to have good knowledge,
there are areas of gap in the quality of asthma care with regards to standard
guideline. There is need for constant training and re-training of physicians in
order to keep them up to date with international guidelines. In addition,
increase access to diagnostic facilities and adapting international guideline to
local realities will help improve standard of Asthma care.
PMID- 28513516
TI - Admission hyperglycemia an independent predictor of outcome in acute ischemic
stroke: A longitudinal study from a tertiary care hospital in South India.
AB - BACKGROUND: Stroke is one of the important causes of long-term disability-related
deaths worldwide. Incidence and prevalence of stroke have been steadily
increasing in India. Increasing interest has been focused on the role of
admission hyperglycemia in the evolution of acute ischemic stroke. Very few
studies were conducted in south India; hence, we intended to do this study.
METHODS: A total of 198 patients with acute ischemic stroke were included in a
hospital-based longitudinal study to identify the independent factors
(demographic, clinical, and biochemical parameters) associated with poor outcome
(functional impairment-mRS >= 3 and mortality at 90 days of follow-up. RESULTS:
Nearly, 75% of the patients presented with moderate-to-severe stroke. Out of the
198 patients, 117 (59%) had severe disability at admission. At 90 days of follow
up, it was observed that only 10 (5.5%) had severe disability. Patients with
hyperglycemia exhibited greater functional impairment, that is, 96 out of 111
study subjects had modified Rankin score (mRS) >=3, than those with normoglycemia
(P < 0.0001). Mortality was high in hyperglycemics when compared with
normoglycemics, that is, out of the 20 deaths, 13 patients had hyperglycemia and
seven had normoglycemia at presentation (P < 0.015). Logistic regression analysis
predicted that higher capillary blood glucose at first presentation, moderate-to
severe stroke, poor drug compliance, stress hyperglycemia, and newly detected
diabetes mellitus were associated with poor functional outcome at 90 days of
follow-up. CONCLUSION: Stress hyperglycemia in stroke was associated with higher
risk of poor functional outcome in acute ischemic stroke. Hyperglycemia at stroke
onset without prior history of diabetes mellitus have particularly poor
prognosis, than those with hyperglycemia in known diabetes.
PMID- 28513517
TI - Comparison of arch width changes following orthodontic treatment with and without
extraction using three-dimensional models.
AB - OBJECTIVE: To compare the arch width changes in patients treated fixed
orthodontic mechanics without extraction (Group 1), with upper and lower first
premolar extractions (Group 2), and with upper first premolar extraction only
(Group 3). MATERIALS AND METHODS: The study was conducted with pre- and post
treatment digital models from 240 patients. Anterior, middle, and posterior
distances were measured on pre- and post-treatment models. At T1 measurements,
the distance among the canine cusp tips, the second premolar buccal cusp tips,
and the first molar mesiobuccal cusp tips were measured. In addition, the
distance (D) between the intercanine and intermolar lines and the distance (D')
between the interpremolar and intermolar lines were defined on the anatomic y
axis, and this distance was maintained in calculating posttreatment measurements
(T2). Mandibular and maxillary arch width changes were evaluated within and
between groups. RESULTS: Anterior, middle, and posterior arch widths increased
significantly in Groups 1 and 3. Maxillary anterior and middle arch widths also
increased in Group 2, but the increases were not statistically significant.
Changes in maxillary anterior and middle arch widths were higher in Groups 1 and
3 when compared to Group 2. However, there was no statistically significant
difference in mandibular arch changes between the groups. CONCLUSION: Extraction
treatment mechanics did not cause narrow dental arches, but nonextraction
treatment increased arch width in all 3 measurements. Treatments with only upper
arch extraction showed similar results with nonextraction treatment.
PMID- 28513518
TI - Firearm injuries received in emergency room of a Nigerian Teaching Hospital:
Aanalysis of pattern, morbidity, and mortality.
AB - BACKGROUND: The morbidity and mortality associated with civilian firearm injury
in developing countries is appreciable. The increasing incidence of gunshot
casualties received in hospital emergency rooms is an emerging concern. The aim
of this study was to determine the pattern and outcome of firearm injuries in a
civilian setting of a developing country. MATERIALS AND METHOD: This was a
retrospective analysis of data on the entire patients with firearm injury
received in the emergency room of Federal Teaching Hospital Abakaliki from
January 2005 to December 2014. RESULTS: There were 214 casualties, male-to-female
ratio was 8:1, and mean age was 31.7 +/- 0.80 years. The causes of injuries were
armed robbery (59.9%), assault (33.6%), and accidental (6.5%). The incidence of
armed robbery-related injury peaked in May and was higher in rainy season (P <
0.018), urban areas (P < 0.001) and at night-time (P < 0.033), whereas the
incidence of assault-related injury peaked in April and was higher in dry season
in rural areas and at day-time. Duration of hospital admission ranged from 1 to
184 days and mean was 16 days. Prolonged duration of hospital admission
correlated with perforating wound (P < 0.001), high-velocity gunshot (P < 0.001),
fractures (P < 0.001) and wound infection (P < 0.001). Preventable death rate was
high, although mortality rate was 5.6%. A high mortality rate correlated with
visceral injury (P < 0.001) and hypovolaemic shock (P < 0.001). CONCLUSION: The
temporal distribution of firearm injury varies in location and aetiology of
gunshot. This and the factors for relatively high morbidity and preventable death
rate observed call for preventive strategies as well as improvement in pre
hospital and emergency room care.
PMID- 28513519
TI - Attitude and knowledge of family medicine practitioners towards the association
between periodontal disease and obesity.
AB - OBJECTIVES: To assess the attitude and knowledge of family medicine practitioners
(FMPs) towards the association between periodontal disease and obesity. MATERIALS
AND METHODS: A cross-sectional study was performed and a 13-item survey
questionnaire was given to FMPs practicing in 12 different teaching hospitals in
Karachi, Pakistan. The questions were aimed at exploring the knowledge of FMP's
regarding the association of obesity and periodontal disease and their attitude
towards the association of obesity and periodontal disease. Chi-square and
Spearman co-efficient were conducted to compare subgroups and correlate factors
with the knowledge score of FMPs. RESULTS: A total of 314 questionnaires were
completed (response rate = 92%). Median age of participants was 41 years and 57%
were females. Almost 61% of FMPs answered all the knowledge questions correctly
and 64% reported moderate understanding of the association between periodontal
health and obesity. Nearly 73% FMPs inquired from obese patients regarding the
periodontal disease and more than half (58%) refer patients to a dentist for
evaluation. More than half of FMPs perform periodontal disease screening. Nearly
all FMPs considered informing obese patients regarding periodontal disease as one
of their roles. CONCLUSIONS: FMP's play an important role in the early diagnosis,
prevention and treatment of periodontal conditions in obese patients. More than
two thirds of FMPs showed good knowledge of the association of obesity and
periodontal disease. The attitudes of FMPs towards assessing and referring obese
patients at a risk of having periodontal disease were reassuring.
PMID- 28513520
TI - Clinical assessment of mineral trioxide aggregate in the treatment of deep
carious lesions.
AB - OBJECTIVE: This clinical study aimed to assess the effectiveness of mineral
trioxide aggregate (MTA) and calcium hydroxide (Ca[OH]2) in the treatment of deep
carious lesions using the direct complete caries excavation technique. SUBJECTS
AND METHODS: Hundred permanent molars/premolars were capped either with Ca (OH)2
(n = 49) or MTA (n = 51) and restored with composite resin in 73 patients.
Periapical radiographs were taken prior to the treatment, at 6 months and 12
months. Two calibrated examiners clinically and radiographically assessed the
periapical pathology and pulpal symptoms. Inter-group comparisons of the observed
values were analyzed using Fisher's exact test. Significance was predetermined at
alpha = 0.05. RESULTS: Recall rates were 100% at 6 and 12 months. Four teeth
capped with Ca(OH)2 (two each at the end of 6 and 12 months) and one tooth capped
with MTA (at the end of 12 months) received endodontic emergency treatment
because of symptoms of irreversible pulpitis that were clinically and/or
radiographically established. There was no significant difference between the
protection of the tooth vitality and pulp capping agents at 6 and 12 months (P =
0.238, P = 0.606, respectively). CONCLUSION: Both materials were clinically
applicable at the end of 12 months.
PMID- 28513521
TI - Otorhinolaryngological emergencies in a Tertiary Hospital in Port Harcourt.
AB - BACKGROUND: Emergencies are not uncommon in a typical otorhinolaryngological
(ORL) clinic. The knowledge of the profile and prevalence of these emergencies
will go a long way in helping to equip as well as aid proper and prompt
management of these conditions so as to reduce their morbidity and mortality.
PATIENTS AND METHODS: A descriptive retrospective 8 years review of all patients
that presented to the ENT Surgery Department from January 2004 to December 2012.
This includes referrals from the accident and emergency as well as the children
emergency ward. The patients case files, the ward, and theatre records were the
source of data. Data collected included; age, sex, presentations, diagnosis, and
management. RESULTS: There were a total number of 5660 patients that presented as
emergencies, however only 2160 cases were real emergencies. Males were 1328 and
females 832 with a ratio of 1.6:1. The age ranged from 6 months to 70 years. The
age range 0-10 years were the most affected 670 (31.02%) followed by age range 21
30 years 534 (24.72%). The least was 61-70 years 26 (1.20%). Foreign body
aspiration/ingestion/insertion was the commonest emergency 900 cases (41.7%)
followed by trauma 650 (30.09%). There were five cases (0.23%) of mortality
recorded. Respiratory distresses from upper airway obstruction, dysphagia, and
odynophagia were the common presentations. Direct laryngoscopy, esophagoscopy,
and tracheostomy were the commonest form of management. CONCLUSION: ORL
emergencies are common. The pediatric age group is the most affected; foreign
body and trauma comprise the commonest emergency in our environment.
PMID- 28513522
TI - Comparison between olfactory function of pregnant women and non-pregnant women in
reproductive age group in Ibadan, Nigeria.
AB - BACKGROUND: Pregnant women require normal olfactory function in order to develop
good appetite for healthy living and normal fetal development. This study was
carried out to investigate and compare olfactory function of pregnant women with
non-pregnant women. METHODS: This was a case control study of women in
reproductive age group at the University College Hospital, Ibadan, Nigeria from
July 2014 to February 2015. Consecutive 70 pregnant women and 70 non-pregnant
women (controls) without rhinologic symptoms were studied. A structured
questionnaire was administered to obtain participants' information on socio
demographics, pregnancy history, and ability to perceive smell. They subjectively
rated their olfactory function on a visual analogue scale of 0 - 100. Olfactory
threshold (OT), discrimination (OD), identification (OI) scores and TDI of both
groups were determined with"Sniffin' sticks"kits and compared. The level of
significance was P<0.05. RESULTS: The mean age of the pregnant women was 30.5+/
3.9years and control was 28.5+/-6.6years. There were more pregnant women (7.1%)
with hyposmia than the non-pregnant women (2.9%). The subjective rating of
olfactory function was 68.2+/-24.9 (median 70) and 72.3+/-21.6 (median 69) in
pregnant women and controls respectively. The mean OT, OD, OI, TDI scores were
higher in pregnant women than the controls. However, it was only in OI (P=0.000)
and TDI (P=0.012) that the differences were significant. CONCLUSIONS: Pregnant
women have olfactory dysfunction more than the non-pregnant women of reproductive
age group. Also, they have tendency to develop loss of cognitive olfactory
information more than the non-pregnant women.
PMID- 28513523
TI - The efficacy of sequential therapy in eradication of Helicobacter pylori in
Turkey.
AB - BACKGROUND AND AIM: Most of the studies about sequential therapy that have been
reported from Turkey were levofloxacin based. We aimed to compare the
Helicobacter pylori (H. pylori) eradication rates of standard triple, sequential
and quadruple therapies including claritromycin regimes in this study. MATERIALS
AND METHODS: A total of 160 patients with dyspeptic symptoms were enrolled to the
study. The patients were randomized to four groups of treatment protocols. And 40
patients received standard triple therapy for 2 weeks, 40 patients received
bismuth containing quadruple therapy for 2 weeks, 40 patients received 5 + 5
clarithromycin-based sequential therapy, and 40 patients received 7 + 7
clarithromycin-based sequential therapy. H. pylori eradication was assessed by C
14 urea breath test 4 weeks after therapy. RESULTS: Out of 160 patients with H.
pylori infection, 131 (81.9%) were eradicated successfully and 29 (18.1%) failed
to eradicate H. pylori infection. H. pylori eradication was achieved in 28 of 40
patients receiving standard triple therapy (70%), in 33 of 40 patients receiving
quadruple therapy (82.5%), in 37 of 40 patients receiving 5 + 5 sequential
therapy (92.5%), and in 33 of 40 patients receiving 7 + 7 sequential therapy (82.
5%). Statistics revealed that 5 + 5 sequential therapy led to significantly
higher H. pylori eradication rates compared with that of standard triple therapy
(P = 0.019). There was no statically difference between 5 + 5 sequential therapy
and the other therapy groups' eradication rates, but it was higher than all of
the protocols. H. pylori eradication rate with sequential therapy in our patients
with nonulcer dyspepsia was higher than those of patients with standard therapy
(93% versus 82%, respectively, P>0.05). CONCLUSION: 5 + 5 sequential therapy was
associated with significantly higher eradication rate of H. pylori compared with
standard triple therapy in our study cohort.
PMID- 28513524
TI - Ureterolithiasis: Management in an environment with limited facilities.
AB - BACKGROUND: In the past 2-3 decades, there has been a dramatic development in the
techniques of stone removal. This study highlights the management of symptomatic
ureteral stones in an environment without such facilities. MATERIALS AND METHODS:
Sixty-nine patients, comprising 53 (76.8%) males and 16 (23.2%) females,
diagnosed of symptomatic ureteric calculi within the study period in two tertiary
health institutions were included in the study. Thorough history taking and
physical examinations were performed. Extensive laboratory investigations using
blood and urine specimens were carried out. Imaging studies, ultrasonography,
intravenous urography, and computerized tomographic scan were used to locate the
position and size of the calculi. RESULTS: Forty-six (66.7%) patients presented
with excruciating flank ureteric colic radiating to the groin in 16 (23.2%)
patients and hematuria in 62 (89.9%) patients. Bilateral ureteric calculi
occurred in 3 (4.3%) patients. Eleven (15%) stones passed spontaneously. 33
(47.8%) patients had uneventful open surgery. The stones were mixed in nature.
CONCLUSION: Management of ureteric stones in our environment is affected by delay
in presentation, low level of awareness of urinary stone disease, lack of modern
endourological equipment, and paucity of urological surgeons. Finally, medical
treatment should be explored for stones below 10 mm in size.
PMID- 28513525
TI - Rehabilitation effect of exercise with soft tissue manipulation in patients with
lumbar muscle strain.
AB - OBJECTIVE: To study the rehabilitation effect of exercise with soft tissue
manipulation therapy for patients with lumbar muscle strain. METHODS: Patients
with lumbar muscle strain who met the inclusion criteria for study were randomly
divided into control and experimental groups. Conventional therapy (i.e., triple
therapy of needle, moxibustion, and cupping jar) was implemented for control
group patients with lumbar muscle strain, whereas the combination therapy of
exercise with manipulation was implemented for experimental group patients with
lumbar muscle strain. Pain levels of the two groups of patients were graded using
the VAS score, and finally, the rehabilitation effect of the two groups of
patients was evaluated. Comparative analysis was performed using SPSS17.0
software, t-test, variance and chi2 test, and other statistical methods. RESULTS:
After treatment, there is a significant difference in average visual analogue
scale (VAS) score between experimental group and control group, which meets P <
0.05; difference in joint range of motion between experimental group patients and
control group patients was P < 0.05; the total treatment efficiency of
experimental group patients was 99%, whereas that of control group was 79%.
CONCLUSION: Rehabilitation effect of exercise with soft tissue manipulation
therapy for lumbar muscle strain is more significant.
PMID- 28513526
TI - Cecal carcinoid tumor in a nigerian man: A case report and review of literature.
AB - Carcinoid tumors are rare neuroendocrine tumors that have been reported in a wide
range of organs but most commonly involve the gastrointestinal tract (stomach,
ileum, appendix, and colon), and rarely ovary and thymus. We present a case of a
56-year-old Nigerian man with a cecal carcinoid tumor that was surgically
removed. A 56-year-old Nigerian man, presented to our hospital with a year
history of right-sided lower abdominal fullness, audible bowel sounds, occasional
diarrhea, nausea, vomiting, and epigastric pain. There was no history of
hematochezia or passage of melena stool. Colonoscopy revealed a cecal mass
occupying more than two-thirds of the cecal lumen. Histology confirmed carcinoid
tumor (well-differentiated neuroendocrine tumor), which was surgically removed.
Carcinoid tumors are slow growing rare neuroendocrine tumors. Mortality is low if
it is diagnosed early.
PMID- 28513527
TI - Management of pediatric mandibular fracture using orthodontic vacuum-formed
thermoplastic splint: A case report and review of literature.
AB - Fractures of the mandible are relatively less frequent in children when compared
to adults. The anatomic features of children are protected. Children have a
higher adaptation to maxillofacial fractures compared to adults. Treatment
principles of mandibular fractures in children differ from that of adults due to
concerns regarding mandibular growth and the developing dentition. A case of a 6
year-old boy with fractured mandibular symphysis managed by closed reduction
using a vacuum formed thermoplastic splint and circummandibular wiring is
presented. This article also provides a review of the literature regarding the
management of mandibular fracture in young children.
PMID- 28513528
TI - Complete upper urinary tract obstruction caused by penetrating pellet injury of
the ureterintroduction.
AB - Ureteral injuries due to gunshots are tend to be misdiagnosed because of
concomitant vascular and intraabdominal organ wounds. Our case is a 23-year-old
man who was admitted to the hospital with multiple abdominal gunshot wounds.
Laboratory findings showed worsening anemia, and the computed tomography (CT)
scan showed multiple lead bullets inside the abdomen and retroperitoneum. Patient
was then taken to the operation room for laparatomy. There were many intestinal
injuries and also a stable retroperitoneal hematoma. There was no ureteral injury
mentioned in the operation note or the initial CT report. Two weeks after this
operation, the patient developed significant urine leakage from the abdominal
wounds. Ureteral J stent placement was our first choice of treatment. This was
complicated with a late ureteral obstruction. The final treatment was an
ureteroureterostomy. Diagnosing ureteral injuries due to traumatic causes can be
hard in most of the cases. Physicians should consider early evaluation of the
patient for ureteral leakage if there is suspicion about ureteral injury.
PMID- 28513529
TI - Total gastric necrosis: A case report and literature review.
AB - Total gastric necrosis is a rare disease and easy to misdiagnose. Here we report
a rare case of total gastric necrosis. The patient, an 89-year-old male, had
epigastric pain for 5 days. He was transferred to our hospital because of
intraperitoneal hemorrhage and hypovolemic shock. We performed an emergency
laparotomy. During the surgery, we found a total of 3500ml unclotted blood in the
abdomen, splenic infarction and gastric necrosis. Total gastrectomy with Roux-en
Y esophagojejunostromy and splenectomy was performed. However, the patient died
on the second day after the surgery. This case suggests that surgical treatment
should be performed as early as possible when ischemia of abdominal organs is
suspected.
PMID- 28513530
TI - An analysis of child deaths by suicide in Queensland Australia, 2004-2012. What
are we missing from a preventative health services perspective?
AB - BACKGROUND: This article analyzes case descriptions of child suicides from 2004
to 2012 to inform future policy and practice. METHODS: Quantitative data and case
descriptions for 159 child suicides (less than 18 years) in Queensland,
Australia, were analyzed quantitatively using SPSS and qualitatively using
automated content analysis (Leximancer). RESULTS: More than three quarters of
child suicides involved hanging and 81% of suicides occurred in the family home.
Less than 20% of the deceased left a note, however there was evidence of planning
in 54% of cases. Most common triggering events were family conflicts.
CONCLUSIONS: Effective suicide prevention interventions require a comprehensive
understanding of risk factors. Quality of case descriptions varied widely, which
can hamper injury prevention efforts through an incomplete understanding of
characteristics of and important factors in child suicide. Additional attention
and resources dedicated to this public health issue could enhance the development
and implementation of effective intervention strategies targeting child and
adolescent suicide.
PMID- 28513531
TI - Who should lead a trauma team: Surgeon or non-surgeon? A systematic review and
meta-analysis.
AB - BACKGROUND: Presence of a trauma team leader (TTL) in the trauma team is
associated with positive patient outcomes in major trauma. The TTL is
traditionally a surgeon who coordinates the resuscitation and ensures adherence
to Advanced Trauma Life Support (ATLS) guidelines. The necessity of routine
surgical leadership in the resuscitative component of trauma care has been
questioned by some authors. Therefore, it remains controversial who should lead
the trauma team. We aimed to evaluate outcomes associated with surgeon versus non
surgeon TTLs in management of trauma patients. METHODS: In accordance with
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
statement standards, we performed a systematic review. Electronic databases
MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials
(CENTRAL) were searched to identify randomized and non-randomized studies
investigating outcomes associated with surgeon versus non-surgeon TTL in
management of trauma patients. The Newcastle-Ottawa scale was used to assess the
methodological quality and risk of bias of the selected studies. Fixed-effect
model was applied to calculate pooled outcome data. RESULTS: Three retrospective
cohort studies, enrolling 2,519 adult major trauma patients were included. Our
analysis showed that there was no difference in survival [odds ratio (OR): 0.82,
95% confidence interval (CI) 0.61-1.10, P=0.19] and length of stay when trauma
team was led by surgeon or non-surgeon TTLs; however, fewer injuries were missed
when the trauma team was led by a surgeon (OR: 0.48, 95% CI 0.25-0.92, P=0.03).
CONCLUSIONS: Despite constant debate, the comparative evidence about outcomes
associated with surgeon and non-surgeon trauma team leader is insufficient. The
best available evidence suggests that there is no significant difference in
outcomes of surgeon or non-surgeon trauma team leaders. High quality randomized
controlled trials are required to compare the effectiveness of surgeon and non
surgeon trauma team leaders in order to resolve the controversy about who should
lead the trauma team. Clinically significant missed injuries should be considered
as important outcome in future studies.
PMID- 28513532
TI - Natural Killer Cells Response to IL-2 Stimulation Is Distinct between Ascites
with the Presence or Absence of Malignant Cells in Ovarian Cancer Patients.
AB - Peritoneal ascites are a distinguishable feature of patients with advanced
epithelial ovarian cancer (EOC). The presence of different lymphocyte subsets has
been reported in EOC-associated ascites, which also can or not contain malignant
cells. The goal of this study was to analyze the functional characteristics of
natural killer (NK) cells from EOC-associated ascites in terms of their
expression of activating receptors and ascites' contents of lymphocyte subtypes,
cytokine profile and presence of EOC cells. NK cell function was evaluated by the
expression of the degranulation marker CD107a in resting and interleukin (IL)-2
stimulated NK cells from ascites and blood. Degranulation of NK cells from EOC
cell-free ascites was significantly (p < 0.05) higher than all the other groups,
either in their resting state or after IL-2 stimulation, suggesting a previous
local stimulation. In contrast, treatment with IL-2 had no effect on NK cells
from ascites with EOC cells. The amount of regulatory T cells was significantly
higher in ascites with EOC cells compared to EOC cell-free ascites. Ascites with
EOC cells also had higher levels of tumor necrosis factor (TNF)-alpha, suggesting
inflammation related to the malignancy. In conclusion, the functional performance
of NK cells was distinct between EOC cell-free ascites and ascites with EOC
cells. The impairment of NK cell response to IL-2 in ascites with EOC cells was
consistent with an immunosuppressive tumor microenvironment.
PMID- 28513533
TI - Deleterious Metabolic Effects of High Fructose Intake: The Preventive Effect of
Lactobacillus kefiri Administration.
AB - Modern lifestyle and diets have been associated with metabolic disorders and an
imbalance in the normal gut microbiota. Probiotics are widely known for their
health beneficial properties targeting the gut microbial ecosystem. The aim of
our study was to evaluate the preventive effect of Lactobacillus kefiri (L.
kefiri) administration in a fructose-rich diet (FRD) mice model. Mice were
provided with tap water or fructose-added (20% w/v) drinking water supplemented
or not with L. kefiri. Results showed that probiotic administration prevented
weight gain and epidydimal adipose tissue (EAT) expansion, with partial reversion
of the adipocyte hypertrophy developed by FRD. Moreover, the probiotic prevented
the increase of plasma triglycerides and leptin, together with the liver
triglyceride content. Leptin adipocyte secretion was also improved by L. kefiri,
being able to respond to an insulin stimulus. Glucose intolerance was partially
prevented by L. kefiri treatment (GTT) and local inflammation (TNFalpha; IL1beta;
IL6 and INFgamma) was completely inhibited in EAT. L. kefiri supplementation
generated an impact on gut microbiota composition, changing Bacteroidetes and
Firmicutes profiles. Overall, our results indicate that the administration of
probiotics prevents the deleterious effects of FRD intake and should therefore be
promoted to improve metabolic disorders.
PMID- 28513536
TI - Resonance Rayleigh Scattering and SERS Spectral Detection of Trace Hg(II) Based
on the Gold Nanocatalysis.
AB - Mercury (Hg) is a heavy metal pollutant, there is an urgent need to develop
simple and sensitive methods for Hg(II) in water. In this article, a simple and
sensitive resonance Rayleigh scattering (RRS) method was developed for
determination of 0.008-1.33 umol/L Hg, with a detection limit of 0.003 MUmol/L,
based on the Hg(II) regulation of gold nanoenzyme catalysis on the HAuCl4-H2O2 to
form gold nanoparticles (AuNPs) with an RRS peak at 370 nm. Upon addition of
molecular probes of Victoria blue B (VBB), the surface-enhanced Raman scattering
(SERS) peak linearly decreased at 1612 cm-1 with the Hg(II) concentration
increasing in the range of 0.013-0.5 MUmol/L. With its good selectivity and good
accuracy, the RRS method is expected to be a promising candidate for determining
mercury ions in water samples.
PMID- 28513535
TI - Characterization of Chinese Unifloral Honeys Based on Proline and Phenolic
Content as Markers of Botanical Origin, Using Multivariate Analysis.
AB - The phenolic and proline content were determined in honey samples of different
floral origins (rapeseed, sunflower, buckwheat and Codonopsis) from five
different regions of China. The phenolic and proline profile of these samples
were used to construct a statistical model to distinguish honeys from different
floral origins. Significant differences were identified among the studied honey
samples from multivariate chemometric methods. The proline content varied among
the four types of honeys, with the values decreasing in the order: buckwheat >
Codonopsis > sunflower > rapeseed. Rapeseed honeys contained a high level of
benzoic acid, while rutin, p-coumaric acid, p-hydroxybenzoic acid were present at
relatively high levels in buckwheat honeys. Principal component analysis (PCA)
revealed that rapeseed honey could be distinguished from the other three
unifloral honeys, and benzoic acid, proline and kaempferol could serve as
potential floral markers. Using 18 phenolic compounds and proline the honey
samples were satisfactorily classified according to floral origin at 94% correct
prediction by linear discriminant analysis (LDA). The results indicated that
phenolic compounds and proline were useful for the identification of the floral
origin of the four type honeys.
PMID- 28513537
TI - Computational Predictions for Single Chain Chalcogenide-Based One-Dimensional
Materials.
AB - Exfoliation of multilayered materials has led to an abundance of new two
dimensional (2D) materials and to their fabrication by other means. These
materials have shown exceptional promise for many applications. In a similar
fashion, we can envision starting with crystalline polymeric (multichain)
materials and exfoliate single-chain, one-dimensional (1D) materials that may
also prove useful. We use electronic structure methods to elucidate the
properties of such 1D materials: individual chains of chalcogens, of silicon
dichalcogenides and of sulfur nitrides. The results indicate reasonable
exfoliation energies in the case of polymeric three-dimensional (3D) materials.
Quantum confinement effects lead to large band gaps and large exciton binding
energies. The effects of strain are quantified and heterojunction band offsets
are determined. Possible applications would entail 1D materials on 3D or 2D
substrates.
PMID- 28513534
TI - Unraveling Prion Protein Interactions with Aptamers and Other PrP-Binding Nucleic
Acids.
AB - Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative
disorders that affect humans and other mammals. The etiologic agents common to
these diseases are misfolded conformations of the prion protein (PrP). The
molecular mechanisms that trigger the structural conversion of the normal
cellular PrP (PrPC) into the pathogenic conformer (PrPSc) are still poorly
understood. It is proposed that a molecular cofactor would act as a catalyst,
lowering the activation energy of the conversion process, therefore favoring the
transition of PrPC to PrPSc. Several in vitro studies have described physical
interactions between PrP and different classes of molecules, which might play a
role in either PrP physiology or pathology. Among these molecules, nucleic acids
(NAs) are highlighted as potential PrP molecular partners. In this context, the
SELEX (Systematic Evolution of Ligands by Exponential Enrichment) methodology has
proven extremely valuable to investigate PrP-NA interactions, due to its ability
to select small nucleic acids, also termed aptamers, that bind PrP with high
affinity and specificity. Aptamers are single-stranded DNA or RNA
oligonucleotides that can be folded into a wide range of structures (from harpins
to G-quadruplexes). They are selected from a nucleic acid pool containing a large
number (1014-1016) of random sequences of the same size (~20-100 bases). Aptamers
stand out because of their potential ability to bind with different affinities to
distinct conformations of the same protein target. Therefore, the identification
of high-affinity and selective PrP ligands may aid the development of new
therapies and diagnostic tools for TSEs. This review will focus on the selection
of aptamers targeted against either full-length or truncated forms of PrP,
discussing the implications that result from interactions of PrP with NAs, and
their potential advances in the studies of prions. We will also provide a
critical evaluation, assuming the advantages and drawbacks of the SELEX
(Systematic Evolution of Ligands by Exponential Enrichment) technique in the
general field of amyloidogenic proteins.
PMID- 28513538
TI - Room-Temperature Ammonia Sensor Based on ZnO Nanorods Deposited on ST-Cut Quartz
Surface Acoustic Wave Devices.
AB - Using a seed layer-free hydrothermal method, ZnO nanorods (NRs) were deposited on
ST-cut quartz surface acoustic wave (SAW) devices for ammonia sensing at room
temperature. For a comparison, a ZnO film layer with a thickness of 30 nm was
also coated onto an ST-cut quartz SAW device using a sol-gel and spin-coating
technique. The ammonia sensing results showed that the sensitivity, repeatability
and stability of the ZnO NR-coated SAW device were superior to those of the ZnO
film-coated SAW device due to the large surface-to-volume ratio of the ZnO NRs.
PMID- 28513540
TI - Enterotoxigenic Escherichia coli Flagellin Inhibits TNF-Induced NF-kappaB
Activation in Intestinal Epithelial Cells.
AB - Enterotoxigenic Escherichia coli (ETEC) causes childhood diarrhea in developing
countries. ETEC strains produce the heat-labile enterotoxin (LT) and/or heat
stable enterotoxins (ST) and encode a diverse set of colonization factors used
for adherence to intestinal epithelial cells. We previously found that ETEC
secretes a heat-stable protein we designated as ETEC Secreted Factor (ESF) that
inhibits the extent of NF-kappaB activation normally induced by tumor necrosis
factor alpha (TNF). Here we fractionated ETEC supernatants using fast protein
liquid chromatography (FPLC) and determined that ETEC flagellin was necessary and
sufficient to protect IkappaBalpha from degradation in response to TNF
stimulation. These data suggest a potentially novel mechanism by which ETEC may
evade the host innate immune response by down-regulating NF-kappaB-dependent host
responses.
PMID- 28513541
TI - Promoting Healthy Lifestyle and Well-Being in Adolescents through Outdoor
Physical Activity.
AB - Health-enhancing physical activities (PA) performed outdoors could markedly
contribute to the adoption of a healthy lifestyle in adolescence. The differences
between PA preferences and actual opportunities for these PA are an issue that
has received frequent attention. To date, the extent to which these differences
are reflected in adolescents meeting PA recommendations and their well-being has
not been explored. In total, 10,086 respondents took part in an on-line research
project regarding PA preferences. Of them, 2446 also completed the International
Physical Activity Questionnaire (Long Form) and the World Health Organization
(WHO) W-5 questionnaire to assess well-being. Finally, 1278 of these respondents
were involved in objective PA monitoring using pedometers. The study aimed to
explore the prevalence and trends regarding outdoor PA. Moreover, we assessed
whether the agreement between preferred PA and PA actually undertaken was
associated with higher odds for meeting PA recommendations and achieving a higher
level of well-being. Of a selection of outdoor activities, Czech and Polish boys
preferred cycling, swimming, and downhill skiing, while girls preferred swimming
activities, skating, and cycling. The agreement between preferred and PA actually
undertaken was associated with higher odds for meeting the weekly PA
recommendations and higher levels of well-being both in boys and girls.
Evaluation of outdoor PA preferences and taking these preferred activities into
account when forming conditions for them was important in the efficient promotion
of the physical and mental health of adolescents.
PMID- 28513542
TI - Biomimetic Synthesis of Resveratrol Trimers Catalyzed by Horseradish Peroxidase.
AB - Biotransformation of trans-resveratrol and synthetic (+/-)-epsilon-viniferin in
aqueous acetone using horseradish peroxidase and hydrogen peroxide as oxidants
resulted in the isolation of two new resveratrol trimers (3 and 4), one new
resveratrol derivative (5) with a dihydrobenzofuran skeleton, together with two
known stilbene trimers (6 and 7), and six known stilbene dimers (8-13). Their
structures and relative configurations were identified through spectral analysis
and possible formation mechanisms were also discussed. Among these oligomers,
trimers 6 and 7 were obtained for the first time through direct transformation
from resveratrol. Results indicated that this reaction is suitable for the
preparation of resveratrol oligomers with a complex structure.
PMID- 28513539
TI - The Interplay between Oncogenic Signaling Networks and Mitochondrial Dynamics.
AB - Mitochondria are dynamic organelles that alter their organization in response to
a variety of cellular cues. Mitochondria are central in many biologic processes,
such as cellular bioenergetics and apoptosis, and mitochondrial network
morphology can contribute to those physiologic processes. Some of the biologic
processes that are in part governed by mitochondria are also commonly deregulated
in cancers. Furthermore, patient tumor samples from a variety of cancers have
revealed that mitochondrial dynamics machinery may be deregulated in tumors. In
this review, we will discuss how commonly mutated oncogenes and their downstream
effector pathways regulate the mitochondrial dynamics machinery to promote
changes in mitochondrial morphology as well as the physiologic consequences of
altered mitochondrial morphology for tumorigenic growth.
PMID- 28513543
TI - Chronic Exposure to Uranium from Gestation: Effects on Behavior and Neurogenesis
in Adulthood.
AB - Uranium exposure leads to cerebral dysfunction involving for instance
biochemical, neurochemical and neurobehavioral effects. Most studies have focused
on mechanisms in uranium-exposed adult animals. However, recent data on
developing animals have shown that the developing brain is also sensitive to
uranium. Models of uranium exposure during brain development highlight the need
to improve our understanding of the effects of uranium. In a model in which
uranium exposure began from the first day of gestation, we studied the
neurobehavioral consequences as well as the progression of hippocampal
neurogenesis in animals from dams exposed to uranium. Our results show that 2
month-old rats exposed to uranium from gestational day 1 displayed deficits in
special memory and a prominent depressive-like phenotype. Cell proliferation was
not disturbed in these animals, as shown by 5-bromo-2'deoxyuridine
(BrdU)/neuronal specific nuclear protein (NeuN) immunostaining in the dentate
gyrus. However, in some animals, the pyramidal cell layer was dispersed in the
CA3 region. From our previous results with the same model, the hypothesis of
alterations of neurogenesis at prior stages of development is worth considering,
but is probably not the only one. Therefore, further investigations are needed to
correlate cerebral dysfunction and its underlying mechanistic pathways.
PMID- 28513544
TI - Morphogenetically-Active Barrier Membrane for Guided Bone Regeneration, Based on
Amorphous Polyphosphate.
AB - We describe a novel regeneratively-active barrier membrane which consists of a
durable electrospun poly(epsilon-caprolactone) (PCL) net covered with a
morphogenetically-active biohybrid material composed of collagen and inorganic
polyphosphate (polyP). The patch-like fibrous collagen structures are decorated
with small amorphous polyP nanoparticles (50 nm) formed by precipitation of this
energy-rich and enzyme-degradable (alkaline phosphatase) polymer in the presence
of calcium ions. The fabricated PCL-polyP/collagen hybrid mats are characterized
by advantageous biomechanical properties, such as enhanced flexibility and
stretchability with almost unaltered tensile strength of the PCL net. The
polyP/collagen material promotes the attachment and increases the
viability/metabolic activity of human mesenchymal stem cells compared to cells
grown on non-coated mats. The gene expression studies revealed that cells,
growing onto polyP/collagen coated mats show a significantly (two-fold) higher
upregulation of the steady-state-expression of the angiopoietin-2 gene used as an
early marker for wound healing than cells cultivated onto non-coated mats. Based
on our results we propose that amorphous polyP, stabilized onto a collagen
matrix, might be a promising component of functionally-active barrier membranes
for guided tissue regeneration in medicine and dentistry.
PMID- 28513545
TI - A Study on Immersion and Presence of a Portable Hand Haptic System for Immersive
Virtual Reality.
AB - This paper proposes a portable hand haptic system using Leap Motion as a haptic
interface that can be used in various virtual reality (VR) applications. The
proposed hand haptic system was designed as an Arduino-based sensor architecture
to enable a variety of tactile senses at low cost, and is also equipped with a
portable wristband. As a haptic system designed for tactile feedback, the
proposed system first identifies the left and right hands and then sends tactile
senses (vibration and heat) to each fingertip (thumb and index finger). It is
incorporated into a wearable band-type system, making its use easy and
convenient. Next, hand motion is accurately captured using the sensor of the hand
tracking system and is used for virtual object control, thus achieving
interaction that enhances immersion. A VR application was designed with the
purpose of testing the immersion and presence aspects of the proposed system.
Lastly, technical and statistical tests were carried out to assess whether the
proposed haptic system can provide a new immersive presence to users. According
to the results of the presence questionnaire and the simulator sickness
questionnaire, we confirmed that the proposed hand haptic system, in comparison
to the existing interaction that uses only the hand tracking system, provided
greater presence and a more immersive environment in the virtual reality.
PMID- 28513548
TI - Towards System Calibration of Panoramic Laser Scanners from a Single Station.
AB - Terrestrial laser scanner measurements suffer from systematic errors due to
internal misalignments. The magnitude of the resulting errors in the point cloud
in many cases exceeds the magnitude of random errors. Hence, the task of
calibrating a laser scanner is important for applications with high accuracy
demands. This paper primarily addresses the case of panoramic terrestrial laser
scanners. Herein, it is proven that most of the calibration parameters can be
estimated from a single scanner station without a need for any reference
information. This hypothesis is confirmed through an empirical experiment, which
was conducted in a large machine hall using a Leica Scan Station P20 panoramic
laser scanner. The calibration approach is based on the widely used target-based
self-calibration approach, with small modifications. A new angular
parameterization is used in order to implicitly introduce measurements in two
faces of the instrument and for the implementation of calibration parameters
describing genuine mechanical misalignments. Additionally, a computationally
preferable calibration algorithm based on the two-face measurements is
introduced. In the end, the calibration results are discussed, highlighting all
necessary prerequisites for the scanner calibration from a single scanner
station.
PMID- 28513546
TI - Edible Plants and Their Influence on the Gut Microbiome and Acne.
AB - Acne vulgaris affects most people at some point in their lives. Due to unclear
etiology, likely with multiple factors, targeted and low-risk treatments have yet
to be developed. In this review, we explore the multiple causes of acne and how
plant-based foods and supplements can control these. The proposed causative
factors include insulin resistance, sex hormone imbalances, inflammation and
microbial dysbiosis. There is an emerging body of work on the human gut
microbiome and how it mediates feedback between the foods we eat and our bodies.
The gut microbiome is also an important mediator of inflammation in the gut and
systemically. A low-glycemic load diet, one rich in plant fibers and low in
processed foods, has been linked to an improvement in acne, possibly through gut
changes or attenuation of insulin levels. Though there is much interest in the
human microbiome, there is much more unknown, especially along the gut-skin axis.
Collectively, the evidence suggests that approaches such as plant-based foods and
supplements may be a viable alternative to the current first line standard of
care for moderate acne, which typically includes antibiotics. Though patient
compliance with major dietary changes is likely much lower than with medications,
it is a treatment avenue that warrants further study and development.
PMID- 28513547
TI - Epigenetic Regulation of Telomere Maintenance for Therapeutic Interventions in
Gliomas.
AB - High-grade astrocytoma of WHO grade 4 termed glioblastoma multiforme (GBM) is a
common human brain tumor with poor patient outcome. Astrocytoma demonstrates two
known telomere maintenance mechanisms (TMMs) based on telomerase activity (TA)
and on alternative lengthening of telomeres (ALT). ALT is associated with lower
tumor grades and better outcome. In contrast to ALT, regulation of TA in tumors
by direct mutation and epigenetic activation of the hTERT promoter is well
established. Here, we summarize the genetic background of TMMs in non-malignant
cells and in cancer, in addition to clinical and pathological features of
gliomas. Furthermore, we present new evidence for epigenetic mechanisms (EMs)
involved in regulation of ALT and TA with special emphasis on human diffuse
gliomas as potential therapeutic drug targets. We discuss the role of TMM
associated telomeric chromatin factors such as DNA and histone modifying enzymes
and non-coding RNAs including microRNAs and long telomeric TERRA transcripts.
PMID- 28513549
TI - Brain RNA-Seq Profiling of the Mucopolysaccharidosis Type II Mouse Model.
AB - Lysosomal storage disorders (LSDs) are a group of about 50 genetic metabolic
disorders, mainly affecting children, sharing the inability to degrade specific
endolysosomal substrates. This results in failure of cellular functions in many
organs, including brain that in most patients may go through progressive
neurodegeneration. In this study, we analyzed the brain of the mouse model for
Hunter syndrome, a LSD mostly presenting with neurological involvement. Whole
transcriptome analysis of the cerebral cortex and
midbrain/diencephalon/hippocampus areas was performed through RNA-seq. Genes
known to be involved in several neurological functions showed a significant
differential expression in the animal model for the disease compared to wild
type. Among the pathways altered in both areas, axon guidance, calcium
homeostasis, synapse and neuroactive ligand-receptor interaction, circadian
rhythm, neuroinflammation and Wnt signaling were the most significant.
Application of RNA sequencing to dissect pathogenic alterations of complex
syndromes allows to photograph perturbations, both determining and determined by
these disorders, which could simultaneously occur in several metabolic and
biochemical pathways. Results also emphasize the common, altered pathways between
neurodegenerative disorders affecting elderly and those associated with pediatric
diseases of genetic origin, perhaps pointing out a general common course for
neurodegeneration, independent from the primary triggering cause.
PMID- 28513550
TI - hCG Triggering in ART: An Evolutionary Concept.
AB - Human chorionic gonadotropin (hCG) is no longer a single, omnipotent ovulation
triggering option. Gonadotropin releasing hormone (GnRH) agonist, initially
presented as a substitute for hCG, has led to a new era of administering GnRH
agonist followed by hCG triggering. According to this new concept, GnRH agonist
enables successful ovum maturation, while hCG supports the luteal phase and
pregnancy until placental shift.
PMID- 28513552
TI - A Two-Echelon Cooperated Routing Problem for a Ground Vehicle and Its Carried
Unmanned Aerial Vehicle.
AB - In this paper, a two-echelon cooperated routing problem for the ground vehicle
(GV) and its carried unmanned aerial vehicle (UAV) is investigated, where the GV
travels on the road network and its UAV travels in areas beyond the road to visit
a number of targets unreached by the GV. In contrast to the classical two-echelon
routing problem, the UAV has to launch and land on the GV frequently to change or
charge its battery while the GV is moving on the road network. A new 0-1 integer
programming model is developed to formulate the problem, where the constraints on
the spatial and temporal cooperation of GV and UAV routes are included. Two
heuristics are proposed to solve the model: the first heuristic (H1) constructs a
complete tour for all targets and splits it by GV routes, while the second
heuristic (H2) constructs the GV tour and assigns UAV flights to it. Random
instances with six different sizes (25-200 targets, 12-80 rendezvous nodes) are
used to test the algorithms. Computational results show that H1 performs slightly
better than H2, while H2 uses less time and is more stable.
PMID- 28513551
TI - The Regulatory Capacity of Bivalent Genes-A Theoretical Approach.
AB - Bivalent genes are frequently associated with developmental and lineage
specification processes. Resolving their bivalency enables fast changes in their
expression, which potentially can trigger cell fate decisions. Here, we provide a
theoretical model of bivalency that allows for predictions on the occurrence,
stability and regulatory capacity of this prominent modification state. We
suggest that bivalency enables balanced gene expression heterogeneity that
constitutes a prerequisite of robust lineage priming in somatic stem cells.
Moreover, we demonstrate that interactions between the histone and DNA
methylation machineries together with the proliferation activity control the
stability of the bivalent state and can turn it into an unmodified state. We
suggest that deregulation of these interactions underlies cell transformation
processes as associated with acute myeloid leukemia (AML) and provide a model of
AML blast formation following deregulation of the Ten-eleven Translocation (TET)
pathway.
PMID- 28513554
TI - An Improved Model Predictive Current Controller of Switched Reluctance Machines
Using Time-Multiplexed Current Sensor.
AB - This paper presents a fixed-switching-frequency model predictive current
controller using multiplexed current sensor for switched reluctance machine (SRM)
drives. The converter was modified to distinguish currents from simultaneously
excited phases during the sampling period. The only current sensor installed in
the converter was time division multiplexing for phase current sampling. During
the commutation stage, the control steps of adjacent phases were shifted so that
sampling time was staggered. The maximum and minimum duty ratio of pulse width
modulation (PWM) was limited to keep enough sampling time for analog-to-digital
(A/D) conversion. Current sensor multiplexing was realized without complex
adjustment of either driver circuit nor control algorithms, while it helps to
reduce the cost and errors introduced in current sampling due to inconsistency
between sensors. The proposed controller is validated by both simulation and
experimental results with a 1.5 kW three-phase 12/8 SRM. Satisfied current
sampling is received with little difference compared with independent phase
current sensors for each phase. The proposed controller tracks the reference
current profile as accurately as the model predictive current controller with
independent phase current sensors, while having minor tracking errors compared
with a hysteresis current controller.
PMID- 28513553
TI - Antibacterial Activity of 7-Epiclusianone and Its Novel Copper Metal Complex on
Streptococcus spp. Isolated from Bovine Mastitis and Their Cytotoxicity in MAC-T
Cells.
AB - Mastitis is an inflammation of mammary gland parenchyma that adversely affects
bovine health and dairy production worldwide despite significant efforts to
eradicate it. The aim of this work was to characterize the antimicrobial activity
of 7-epiclusianone (7-epi), a compound extracted from the Rheedia brasiliensis
fruit, its complex with copper against Streptococcus spp. isolated from bovine
mastitis, and to assess their cytotoxicity to bovine mammary alveolar cells (MAC
T). The complex 7-epiclusianone-Cu (7-epi-Cu) was an amorphous green solid with
optical activity. Its vibrational spectrum in the infrared region showed
absorption bands in the high-frequency region, as well as bands that can be
attributed to the unconjugated and conjugated stretching of the free ligand. The
complex was anhydrous. One of the tested bacterial strains was not sensitive to
the compounds, while the other three had MIC values of 7.8 ug mL-1 and minimum
bactericidal concentration (MBC) values between 15.6 and 31.3 ug mL-1. These two
compounds are bacteriostatic, did not cause damage to the cell wall and, at sub
inhibitory concentrations, did not induce bacterial adhesion. The compounds were
not cytotoxic. Based on these results, 7-epi and 7-epi-Cu exhibited desirable
antimicrobial properties and could potentially be used in bovine mastitis
treatment.
PMID- 28513555
TI - Effect of Low-Dose Vitamin D Supplementation on Serum 25(OH)D in School Children
and White-Collar Workers.
AB - OBJECTIVE: Our study aimed to investigate the nutritional vitamin D status of
school children aged 9-15 years and white-collar workers in Zhejiang province,
and evaluate the efficacy of low-dose-oral vitamin D supplementation in both
populations. METHODS: We conducted a prospective controlled trial during March
2014 to November 2015, comparing the efficacy of vitamin D supplements (400
IU/day) with non-intervention for 18 months in school children aged 9-15 years.
Meanwhile, a before-after study was conducted among white-collar workers for 1
year. Serum 25(OH)D concentration was measured at baseline and after vitamin D
supplementation, respectively. RESULTS: At the baseline, 95% of school children
and 84% of adult participants had vitamin D deficiency (<20 ng/mL). In school
children, no difference was observed between the intervention and control groups
with regard to anthropometric data. Serum 25(OH)D concentrations of the school
children intervention group, school children control group and white-collar
workers were 12.77 +/- 3.01 ng/mL, 14.17 +/- 3.59 ng/mL and 16.58 +/- 3.66 ng/mL
at baseline and increased to 17.34 +/- 3.78 ng/mL, 18.04 +/- 4.01 ng/mL and 17.75
+/- 5.36 ng/mL after vitamin D supplementation, respectively. Although, after
adjusting for potential confounders, the 400 IU oral vitamin D supplementation
increased serum 25(OH)D concentration in school children (beta = 0.81, p =
0.0426) as well as in white-collar workers (p = 0.0839), the prevalence of
vitamin D deficiency was still very high among school children (79.23% in
intervention group and 72.38% in control group) and white-collar workers
(76.00%). CONCLUSIONS: High prevalence of vitamin D deficiency was common in
these two study populations. Daily doses of 400 IU oral vitamin D supplementation
was not able to adequately increase serum 25(OH)D concentrations. A suitable
recommendation regarding the level of vitamin D supplementation is required for
this Chinese population.
PMID- 28513556
TI - Microscale Quantitative Analysis of Polyhydroxybutyrate in Prokaryotes Using
IDMS.
AB - Poly(3-hydroxybutyrate) (PHB) is an interesting biopolymer for replacing
petroleum-based plastics, its biological production is performed in natural and
engineered microorganisms. Current metabolic engineering approaches rely on high
throughput strain construction and screening. Analytical procedures have to be
compatible with the small scale and speed of these approaches. Here, we present a
method based on isotope dilution mass spectrometry (IDMS) and propanolysis
extraction of poly(3-hydroxybutyrate) from an Escherichia coli strain engineered
for PHB production. As internal standard (IS), we applied an uniformly labeled
13C-cell suspension, of an E. coli PHB producing strain, grown on U-13C-glucose
as C-source. This internal 13C-PHB standard enables to quantify low
concentrations of PHB (LOD of 0.01 ug/gCDW) from several micrograms of biomass.
With this method, a technical reproducibility of about 1.8% relative standard
deviation is achieved. Furthermore, the internal standard is robust towards
different sample backgrounds and dilutions. The early addition of the internal
standard also enables higher reproducibility and increases sensitivity and
throughput by simplified sample preparation steps.
PMID- 28513557
TI - Calcium Supplement Derived from Gallus gallus domesticus Promotes BMP
2/RUNX2/SMAD5 and Suppresses TRAP/RANK Expression through MAPK Signaling
Activation.
AB - The present study evaluated the effects of a calcium (Ca) supplement derived from
Gallus gallus domesticus (GD) on breaking force, microarchitecture, osteogenic
differentiation and osteoclast differentiation factor expression in vivo in Ca
deficient ovariectomized (OVX) rats. One percent of Ca supplement significantly
improved Ca content and bone strength of the tibia. In micro-computed tomography
analysis, 1% Ca supplement attenuated OVX- and low Ca-associated changes in bone
mineral density, trabecular thickness, spacing and number. Moreover, 1% Ca
supplemented diet increased the expression of osteoblast differentiation marker
genes, such as bone morphogenetic protein-2, Wnt3a, small mothers against
decapentaplegic 1/5/8, runt-related transcription factor 2, osteocalcin and
collagenase-1, while it decreased the expression of osteoclast differentiation
genes, such as thrombospondin-related anonymous protein, cathepsin K and receptor
activator of nuclear factor kappa B. Furthermore, 1% Ca-supplemented diet
increased the levels of phosphorylated extracellular signal-regulated kinase and
c-Jun N-terminal kinase. The increased expression of osteoblast differentiation
marker genes and activation of mitogen-activated protein kinase signaling were
associated with significant increases in trabecular bone volume, which plays an
important role in the overall skeletal strength. Our results demonstrated that 1%
Ca supplement inhibited osteoclastogenesis, stimulated osteoblastogenesis and
restored bone loss in OVX rats.
PMID- 28513558
TI - From Cell to Beak: In-Vitro and In-Vivo Characterization of Chicken Bitter Taste
Thresholds.
AB - Bitter taste elicits an aversive reaction, and is believed to protect against
consuming poisons. Bitter molecules are detected by the Tas2r family of G-protein
coupled receptors, with a species-dependent number of subtypes. Chickens
demonstrate bitter taste sensitivity despite having only three bitter taste
receptors-ggTas2r1, ggTas2r2 and ggTas2r7. This minimalistic bitter taste system
in chickens was used to determine relationships between in-vitro (measured in
heterologous systems) and in-vivo (behavioral) detection thresholds. ggTas2r
selective ligands, nicotine (ggTas2r1), caffeine (ggTas2r2), erythromycin and (+)
catechin (ggTas2r7), and the Tas2r-promiscuous ligand quinine (all three
ggTas2rs) were studied. Ligands of the same receptor had different in-vivo:in
vitro ratios, and the ggTas2r-promiscuous ligand did not exhibit lower in-vivo:in
vitro ratios than ggTas2r-selective ligands. In-vivo thresholds were similar or
up to two orders of magnitude higher than the in-vitro ones.
PMID- 28513559
TI - Detecting and Discriminating Shigella sonnei Using an Aptamer-Based Fluorescent
Biosensor Platform.
AB - In this paper, a Whole-Bacteria SELEX (WB-SELEX) strategy was adopted to isolate
specific aptamers against Shigella sonnei. Real-time PCR amplification and post
SELEX experiment revealed that the selected aptmers possessed a high binding
affinity and specificity for S. sonnei. Of the 21 aptamers tested, the C(t)
values of the SS-3 and SS-4 aptamers (Ct = 13.89 and Ct = 12.23, respectively)
had the lowest value compared to other aptamer candidates. The SS-3 and SS-4
aptamers also displayed a binding affinity (KD) of 39.32 +/- 5.02 nM and 15.89 +/
1.77 nM, respectively. An aptamer-based fluorescent biosensor assay was designed
to detect and discriminate S. sonnei cells using a sandwich complex pair of SS-3
and SS-4. The detection of S. sonnei by the aptamer based fluorescent biosensor
platform consisted of three elements: (1) 5'amine-SS-4 modification in a 96-well
type microtiter plate surface (N-oxysuccinimide, NOS) as capture probes; (2) the
incubation with S. sonnei and test microbes in functionalized 96 assay wells in
parallel; (3) the readout of fluorescent activity using a Cy5-labeled SS-3
aptamer as the detector. Our platform showed a significant ability to detect and
discriminate S. sonnei from other enteric species such as E. coli, Salmonella
typhimurium and other Shigella species (S. flexneri, S. boydii). In this study,
we demonstrated the feasibility of an aptamer sensor platform to detect S. sonnei
in a variety of foods and pave the way for its use in diagnosing shigellosis
through multiple, portable designs.
PMID- 28513561
TI - The Effect of Physicochemical Modification on the Function of Antibodies Induced
by Anti-Nicotine Vaccine in Mice.
AB - Smoking remains one of the major causes of morbidity and mortality worldwide. One
approach to assisting smoking cessation is via anti-nicotine vaccines, composed
of nicotine-like haptens conjugated to a carrier protein plus adjuvant(s). We
have previously shown that the carrier, hapten, linker, hapten load, degree of
conjugate aggregation, and presence of adducts can each influence the function
(nicotine-binding capacity) of the antibody (Ab) induced. Herein, we extend those
findings and show that tertiary structure is also critical to the induction of
functional immune responses and that this can be influenced by conjugation
conditions. We evaluated immunogenicity in mice using six lots of NIC7-CRM, a
conjugate of 5-aminoethoxy-nicotine (Hapten 7), and a single point (glycine 52 to
glutamic acid) mutant nontoxic form of diphtheria toxin, cross-reactive material
197 (CRM197), which were synthesized under different reaction conditions
resulting in conjugates with equivalent molecular characteristics (hapten load,
aggregates, adducts), but a different tertiary structure. When tested in mice,
better functional responses (reduced nicotine in the brain of immunized animals
relative to non-immunized controls) were obtained with conjugates with a more
closed structure than those with an open conformation. These studies highlight
the need for a better understanding of the physicochemical properties of small
molecule conjugate vaccines.
PMID- 28513560
TI - Meta-Chirality: Fundamentals, Construction and Applications.
AB - Chiral metamaterials represent a special type of artificial structures that
cannot be superposed to their mirror images. Due to the lack of mirror symmetry,
cross-coupling between electric and magnetic fields exist in chiral mediums and
present unique electromagnetic characters of circular dichroism and optical
activity, which provide a new opportunity to tune polarization and realize
negative refractive index. Chiral metamaterials have attracted great attentions
in recent years and have given rise to a series of applications in polarization
manipulation, imaging, chemical and biological detection, and nonlinear optics.
Here we review the fundamental theory of chiral media and analyze the
construction principles of some typical chiral metamaterials. Then, the progress
in extrinsic chiral metamaterials, absorbing chiral metamaterials, and
reconfigurable chiral metamaterials are summarized. In the last section, future
trends in chiral metamaterials and application in nonlinear optics are
introduced.
PMID- 28513562
TI - Effects of Growth Media on the Diversity of Culturable Fungi from Lichens.
AB - Microscopic and molecular studies suggest that lichen symbioses contain a
plethora of associated fungi. These are potential producers of novel bioactive
compounds, but strains isolated on standard media usually represent only a minor
subset of these fungi. By using various in vitro growth conditions we are able to
modulate and extend the fraction of culturable lichen-associated fungi. We
observed that the presence of iron, glucose, magnesium and potassium in growth
media is essential for the successful isolation of members from different
taxonomic groups. According to sequence data, most isolates besides the lichen
mycobionts belong to the classes Dothideomycetes and Eurotiomycetes. With our
approach we can further explore the hidden fungal diversity in lichens to assist
in the search of novel compounds.
PMID- 28513563
TI - New Glycosides from the Fruits of Nicandra physaloides.
AB - Three new glycosides (1-3) and 15 known ones (4-18) were isolated and identified
from the fruits of Nicandra physaloides. The structures of these compounds were
established by 1D and 2D NMR spectra and HR-ESI-MS. The compounds (4-18) were the
first time isolated from the Nicandra genus and they (except 8, 10, 14) exhibited
inhibitions on the NO release of LPS-induced RAW 264.7 cells with IC50 values
from 26.9 to 47.5 MUM.
PMID- 28513564
TI - Tetrodotoxin-Producing Bacteria: Detection, Distribution and Migration of the
Toxin in Aquatic Systems.
AB - This review is devoted to the marine bacterial producers of tetrodotoxin (TTX), a
potent non-protein neuroparalytic toxin. In addition to the issues of the ecology
and distribution of TTX-producing bacteria, this review examines issues relating
to toxin migration from bacteria to TTX-bearing animals. It is shown that the
mechanism of TTX extraction from toxin-producing bacteria to the environment
occur through cell death, passive/active toxin excretion, or spore germination of
spore-forming bacteria. Data on TTX microdistribution in toxic organs of TTX
bearing animals indicate toxin migration from the digestive system to target
organs through the transport system of the organism. The role of symbiotic
microflora in animal toxicity is also discussed: despite low toxin production by
bacterial strains in laboratory conditions, even minimal amounts of TTX produced
by intestinal microflora of an animal can contribute to its toxicity. Special
attention is paid to methods of TTX detection applicable to bacteria. Due to the
complexity of toxin detection in TTX-producing bacteria, it is necessary to use
several methods based on different methodological approaches. Issues crucial for
further progress in detecting natural sources of TTX investigation are also
considered.
PMID- 28513566
TI - Neurophysiological Changes Induced by Chronic Toxoplasma gondii Infection.
AB - Although the parasite Toxoplasma gondii is one of the most pervasive neurotropic
pathogens in the world, the host-parasite interactions during CNS infection and
the consequences of neurological infection are just beginning to be unraveled.
The chronic stages of infection have been considered dormant, although several
studies have found correlations of infection with an array of host behavioral
changes. These may facilitate parasite transmission and impact neurological
diseases. During infection, in addition to the presence of the parasites within
neurons, host-mediated neuroimmune and hormonal responses to infection are also
present. T. gondii induces numerous changes to host neurons during infection and
globally alters host neurological signaling pathways, as discussed in this
review. Understanding the neurophysiological changes in the host brain is
imperative to understanding the parasitic mechanisms and to delineate the effects
of this single-celled parasite on health and its contribution to neurological
disease.
PMID- 28513567
TI - Mental Health Service Utilization among Black Youth; Psychosocial Determinants in
a National Sample.
AB - Racial disparity in mental health service utilization (MHSU) persists, and youths
are not an exception to the underutilization of services. Very limited research
has been conducted on the determinants of MHSU among Black youth. Using a
national sample of American Black youth, the current study investigated the
association between demographic factors, socioeconomic status, psychiatric
disorders, and self-rated health (SRH) on MHSU. We also tested the heterogeneity
of the effects of SRH and psychiatric disorders based on ethnicity, gender, and
their intersection. We used data from the National Survey of American Life
Adolescents supplement (NSAL-A), 2003-2004. The study enrolled 1170 Black youth
between 13 and 17 years old including 810 African Americans and 360 Caribbean
Blacks. Age, gender, ethnicity, socioeconomic status, SRH, 12-month psychiatric
disorders (Composite International Diagnostic Interview modified version), and
MHSU (last year) were measured. Logistic regressions were used for data analysis.
Ethnicity (odds ratio (OR) = 0.33, 95% confidence interval (CI) = 0.17-0.65),
subjective socioeconomic status (OR = 1.43, 95% CI = 1.09-1.88), SRH (OR = 2.45,
95% CI = 1.00-6.37), and psychiatric disorders (OR = 2.17, 95% CI = 1.05-4.48)
were associated with MHSU. Age, gender, and objective socioeconomic status were
not associated with MHSU. Gender and ethnicity did not interact with SRH and
psychiatric disorders on MHSU. Actual and perceived need both universally
influence Black youths' likelihood of MHSU, regardless of their ethnicity and
gender. Ethnicity and perceived socioeconomic status also play unique roles in
MHSU. Future research is needed to understand pathways to MHSU for Black youth
who both have and perceive mental health needs. There is also a need to find ways
to promote MHSU for those with a need for mental health services.
PMID- 28513568
TI - Using UPLC-MS/MS for Characterization of Active Components in Extracts of
Yupingfeng and Application to a Comparative Pharmacokinetic Study in Rat Plasma
after Oral Administration.
AB - Yupingfeng (YPF), a famous traditional Chinese medicine, which contains a large
array of compounds, has been effectually used in health protection. A two
dimensional liquid chromatography (2D-LC) combined with quadrupole time-of-flight
mass spectrometry (QTOF-MS) method was firstly established to separate and
identify chemical components in YPF. A total of 33 compounds were identified,
including 15 constituents (flavonoids and saponins) in Astragali radix; seven
constituents (sesquiterpenoids and polysaccharide) in Atractylodis rhizoma; and
11 constituents (chromone and coumarins) in Saposhnikoviae radix. The
corresponding fragmentation pathway of typical substances was investigated. Then,
seven active constituents (astragaloside, calycosin, formononetin,
cimicifugoside, 4-O-beta-d-glucosyl-5-O-methylvisamminol, sec-O-glucosylhamaudol,
and atractylenolide II) derived from three medicinal plants were chosen to
further investigate the pharmacokinetic behavior of YPF formula using ultrahigh
performance liquid chromatography with triple quadrupole mass spectrometry
system. The method was sensitive, accurate and reliable. We also used the area
under the plasma concentration-time curve from zero to infinity (AUC0-infinity)
as weighting factor to make an integrated pharmacokinetic curve. Results show
that the constituents of Saposhnikoviae radix have the best absorption and
pharmacokinetic behavior and may play important role in leading to the changes of
overall therapeutic effects of YPF. Further study is needed to confirm the
association between them.
PMID- 28513570
TI - A Study of the Protective Properties of Iraqi Olive Leaves against Oxidation and
Pathogenic Bacteria in Food Applications.
AB - There is an ancient and prodigious history of olive trees because of their
nutritional, medicinal, and traditional uses. Intensive studies have been
conducted on olive leaves because they have many positive and beneficial effects
for human health. In this study, different solvents were used to examine the
olive leaves for their antioxidant and antimicrobial activities and their
possible food applications. The obtained results showed that the amounts of
phenolic compounds of the olive leaf were 190.44 +/- 0.50, 173 +/- 1.72, 147.78
+/- 0.69, and 147.50 +/- 0.05 mg gallic acid/g extracts using methanol, ethanol,
diethyl ether, and hexanol, respectively. The statistical analysis revealed that
there was a significant difference in the phenolic contents in terms of the used
solvents. The stability of the olive leaves extraction was also studied and the
results indicated that increasing the storage temperature could negatively affect
and encourage the degradation of the phenolic compounds. Furthermore, the olive
leaf extraction was applied to raw sheep meat slides at 0.5%, 1.5%, and 2.5%
(w/v) in order to test its antioxidant and antimicrobial effects. The results
obviously showed that the sample treated with 2.5% olive leaf extract had the
significantly (p < 0.05) lowest Thiobarbituric Acid (TBA) values of 1.92 +/- 0.12
(mg Malonaldehyde MDA/kg) throughout 12 days of cold storage. Moreover, the
results showed that the sample, which was treated with 2.5% olive leaf extract,
had low total bacterial count and total coliform bacteria (6.23 +/- 0.05, 5.2 +/-
0.35 log colony forming unit (CFU)/g, respectively) among the control, 0.5%, and
1.5% olive leaf treated samples throughout 12 days of storage. The phenolic
extracts from the olive leaf extract had significant antioxidant and
antimicrobial activities, which could be used as a source of potential
antioxidant and antimicrobial agents.
PMID- 28513569
TI - Intravenous Arginine Administration Promotes Proangiogenic Cells Mobilization and
Attenuates Lung Injury in Mice with Polymicrobial Sepsis.
AB - This study investigated the influence of intravenous arginine (Arg)
administration on alteration of circulating proangiogenic cells and remote lung
injury in a model of polymicrobial sepsis. Mice were assigned to one normal
control group (NC) and two sepsis groups that were induced by cecal ligation and
puncture (CLP). One of the sepsis groups was injected with saline (SS), whereas
the other (SA) was administered with a single bolus of 300 mg Arg/kg body weight
via the tail vein 1 h after CLP. Septic mice were sacrificed at either 24 or 48 h
after CLP, with their blood and lung tissues collected for analysis. Results
showed that septic groups had higher proangiogenic cells releasing factors and
proangiogenic cells percentage in blood. Also, concentration of inflammatory
cytokines and expression of angiopoietin (Angpt)/Tie-2 genes in lung tissues were
upregulated. Arg administration promoted mobilization of circulating
proangiogenic cells while it downregulated the production of inflammatory
cytokines and expression of Angpt/Tie-2 genes in the lung. The results of this
investigation suggested that intravenous administration of Arg shortly after the
onset of sepsis enhanced the mobilization of circulating proangiogenic cells,
maintained the homeostasis of the Angpt/Tie-2 axis, and attenuated remote organ
injury in polymicrobial sepsis.
PMID- 28513572
TI - Synthesis and Antiradical Activity of Isoquercitrin Esters with Aromatic Acids
and Their Homologues.
AB - Isoquercitrin, (IQ, quercetin-3-O-beta-d-glucopyranoside) is known for strong
chemoprotectant activities. Acylation of flavonoid glucosides with carboxylic
acids containing an aromatic ring brings entirely new properties to these
compounds. Here, we describe the chemical and enzymatic synthesis of a series of
IQ derivatives at the C-6". IQ benzoate, phenylacetate, phenylpropanoate and
cinnamate were prepared from respective vinyl esters using Novozym 435 (Lipase B
from Candida antarctica immobilized on acrylic resin). The enzymatic procedure
gave no products with "hydroxyaromatic" acids, their vinyl esters nor with their
benzyl-protected forms. A chemical protection/deprotection method using Steglich
reaction yielded IQ 4-hydroxybenzoate, vanillate and gallate. In case of p
coumaric, caffeic, and ferulic acid, the deprotection lead to the saturation of
the double bonds at the phenylpropanoic moiety and yielded 4-hydroxy-, 3,4
dihydroxy- and 3-methoxy-4-hydroxy-phenylpropanoates. Reducing capacity of the
cinnamate, gallate and 4-hydroxyphenylpropanoate towards Folin-Ciocalteau reagent
was significantly lower than that of IQ, while other derivatives displayed
slightly better or comparable capacity. Compared to isoquercitrin, most
derivatives were less active in 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical
scavenging, but they showed significantly better 2,2'-azinobis-(3
ethylbenzothiazoline-6-sulfonic acid, ABTS) scavenging activity and were
substantially more active in the inhibition of tert-butylhydroperoxide induced
lipid peroxidation of rat liver microsomes. The most active compounds were the
hydroxyphenylpropanoates.
PMID- 28513571
TI - Fat, Sugar, and Bone Health: A Complex Relationship.
AB - With people aging, osteoporosis is expected to increase notably. Nutritional
status is a relatively easily-modified risk factor, associated with many chronic
diseases, and is involved in obesity, diabetes, and coronary heart disease (CHD),
along with osteoporosis. Nutrients, such as fats, sugars, and proteins, play a
primary function in bone metabolism and maintaining bone health. In Western
nations, diets are generally high in saturated fats, however, currently, the
nutritional patterns dominating in China continue to be high in carbohydrates
from starch, cereals, and sugars. Moreover, high fat or high sugar (fructose,
glucose, or sucrose) impart a significant impact on bone structural integrity.
Due to diet being modifiable, demonstrating the effects of nutrition on bone
health can provide an approach for osteoporosis prevention. Most researchers have
reported that a high-fat diet consumption is associated with bone mineral density
(BMD) and, as bone strength diminishes, adverse microstructure changes occur in
the cancellous bone compartment, which is involved with lipid metabolism
modulation disorder and the alteration of the bone marrow environment, along with
an increased inflammatory environment. Some studies, however, demonstrated that a
high-fat diet contributes to achieving peak bone mass, along with microstructure,
at a younger age. Contrary to these results, others have shown that a high
fructose diet consumption leads to stronger bones with a superior
microarchitecture than those with the intake of a high-glucose diet and, at the
same time, research indicated that a high-fat diet usually deteriorates
cancellous bone parameters, and that the incorporation of fructose into a high
fat diet did not aggravate bone mass loss. High-fat/high-sucrose diets have shown
both beneficial and detrimental influences on bone metabolism. Combined, these
studies showed that nutrition exerts different effects on bone health. Thus, a
better understanding of the regulation between dietary nutrition and bone health
might provide a basis for the development of strategies to improve bone health by
modifying nutritional components.
PMID- 28513573
TI - Nrf2 Inhibits Periodontal Ligament Stem Cell Apoptosis under Excessive Oxidative
Stress.
AB - The present study aimed to analyze novel mechanisms underlying Nrf2-mediated anti
apoptosis in periodontal ligament stem cells (PDLSCs) in the periodontitis
oxidative microenvironment. We created an oxidative stress model with H2O2
treated PDLSCs. We used real-time PCR, Western blotting, TUNEL staining,
fluorogenic assay and transfer genetics to confirm the degree of oxidative stress
and apoptosis as well as the function of nuclear factor-erythroid 2-related
factor 2 (Nrf2). We demonstrated that with upregulated levels of reactive oxygen
species (ROS) and malondialdehyde (MDA), the effect of oxidative stress was
obvious under H2O2 treatment. Oxidative molecules were altered after the H2O2
exposure, whereby the signaling of Nrf2 was activated with an increase in its
downstream effectors, heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1
(NQO1) and gamma-glutamyl cysteine synthetase (gamma-GCS). Additionally, the
apoptosis levels gradually increased with oxidative stress by the upregulation of
caspase-9, caspase-3, Bax and c-Fos levels in addition to the downregulation of
Bcl-2. However, there was no alterations in levels of caspase-8. The enhanced
antioxidant effect could not mitigate the occurrence of apoptosis. Furthermore,
Nrf2 overexpression effectively improved the anti-oxidative levels and increased
cell proliferation. At the same time, overexpression effectively restrained TUNEL
staining and decreased the molecular levels of caspase-9, caspase-3, Bax and c
Fos, but not that of caspase-8. In contrast, silencing the expression of Nrf2
levels had the opposite effect. Collectively, Nrf2 alleviates PDLSCs via its
effects on regulating oxidative stress and anti-intrinsic apoptosis by the
activation of oxidative enzymes.
PMID- 28513574
TI - Transcriptional and Physiological Responses to Nutrient Loading on Toxin
Formation and Photosynthesis in Microcystis Aeruginosa FACHB-905.
AB - An important goal of understanding harmful algae blooms is to determine how
environmental factors affect the growth and toxin formation of toxin-producing
species. In this study, we investigated the transcriptional responses of toxin
formation gene (mcyB) and key photosynthesis genes (psaB, psbD and rbcL) of
Microcystis aeruginosa FACHB-905 in different nutrient loading conditions using
real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR).
Three physio-biochemical parameters (malondialdehyde (MDA), superoxide dismutase
(SOD) and glutathione (GSH)) were also evaluated to provide insight into the
physiological responses of Microcystis cells. We observed an upregulation of mcyB
gene in nutrient-deficient conditions, especially in nitrogen (N) limitation
condition, and the transcript abundance declined after the nutrient were
resupplied. Differently, high transcription levels were seen in phosphorus (P)
deficient treatments for key photosynthesis genes throughout the culture period,
while those in N-deficient cells varied with time, suggesting an adaptive
regulation of Microsystis cells to nutrient stress. Increased contents of
antioxidant enzymes (SOD and GSH) were seen in both N and P-deficient conditions,
suggesting the presence of excess amount of free radical generation caused by
nutrient stress. The amount of SOD and GSH continued to increase even after the
nutrient was reintroduced and a strong correlation was seen between the MDA and
enzyme activities, indicating the robust effort of rebalancing the redox system
in Microcystis cells. Based on these transcriptional and physiological responses
of M. aeruginosa to nutrient loading, these results could provide more insight
into Microcystis blooms management and toxin formation regulation.
PMID- 28513575
TI - Adding Value to Goat Meat: Biochemical and Technological Characterization of
Autochthonous Lactic Acid Bacteria to Achieve High-Quality Fermented Sausages.
AB - Quality and safety are important challenges in traditional fermented sausage
technology. Consequently, the development of a tailored starter culture based on
indigenous microbiota constitutes an interesting alternative. In the present
study, spontaneously fermented goat meat sausages were created and analyzed using
a physicochemical and microbiological approach. Thereafter 170 lactic acid
bacteria (LAB) strains were isolated and preliminary characterized by phenotypic
assays. The hygienic and technological properties, and growth and fermentative
potential of isolates using a goat-meat-based culture medium were evaluated. All
strains proved to have bioprotective features due to their acidogenic metabolism.
Almost all grew optimally in meat environments. LAB isolates presented
proteolytic activity against meat proteins and enriched amino acid contents of
the goat-meat-based model. The most efficient strains were four different
Lactobacillus sakei isolates, as identified by genotyping and RAPD analysis. L.
sakei strains are proposed as optimal candidates to improve the production of
fermented goat meat sausages, creating a new added-value fermented product.
PMID- 28513565
TI - Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways.
AB - The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is
commonly upregulated in cancers such as in non-small-cell lung cancer, metastatic
colorectal cancer, glioblastoma, head and neck cancer, pancreatic cancer, and
breast cancer. Various mechanisms mediate the upregulation of EGFR activity,
including common mutations and truncations to its extracellular domain, such as
in the EGFRvIII truncations, as well as to its kinase domain, such as the L858R
and T790M mutations, or the exon 19 truncation. These EGFR aberrations over
activate downstream pro-oncogenic signaling pathways, including the RAS-RAF-MEK
ERK MAPK and AKT-PI3K-mTOR pathways. These pathways then activate many biological
outputs that are beneficial to cancer cell proliferation, including their chronic
initiation and progression through the cell cycle. Here, we review the molecular
mechanisms that regulate EGFR signal transduction, including the EGFR structure
and its mutations, ligand binding and EGFR dimerization, as well as the signaling
pathways that lead to G1 cell cycle progression. We focus on the induction of
CYCLIN D expression, CDK4/6 activation, and the repression of cyclin-dependent
kinase inhibitor proteins (CDKi) by EGFR signaling pathways. We also discuss the
successes and challenges of EGFR-targeted therapies, and the potential for their
use in combination with CDK4/6 inhibitors.
PMID- 28513577
TI - Optical determination of crystal phase in semiconductor nanocrystals.
AB - Optical, electronic and structural properties of nanocrystals fundamentally
derive from crystal phase. This is especially important for polymorphic II-VI,
III-V and I-III-VI2 semiconductor materials such as cadmium selenide, which exist
as two stable phases, cubic and hexagonal, each with distinct properties.
However, standard crystallographic characterization through diffraction yields
ambiguous phase signatures when nanocrystals are small or polytypic. Moreover,
diffraction methods are low-throughput, incompatible with solution samples and
require large sample quantities. Here we report the identification of unambiguous
optical signatures of cubic and hexagonal phases in II-VI nanocrystals using
absorption spectroscopy and first-principles electronic-structure theory. High
energy spectral features allow rapid identification of phase, even in small
nanocrystals (~2 nm), and may help predict polytypic nanocrystals from
differential phase contributions. These theoretical and experimental insights
provide simple and accurate optical crystallographic analysis for liquid
dispersed nanomaterials, to improve the precision of nanocrystal engineering and
improve our understanding of nanocrystal reactions.
PMID- 28513576
TI - Biofilm is a Major Virulence Determinant in Bacterial Colonization of Chronic
Skin Ulcers Independently from the Multidrug Resistant Phenotype.
AB - Bacterial biofilm is a major factor in delayed wound healing and high levels of
biofilm production have been repeatedly described in multidrug resistant
organisms (MDROs). Nevertheless, a quantitative correlation between biofilm
production and the profile of antimicrobial drug resistance in delayed wound
healing remains to be determined. Microbial identification, antibiotic
susceptibility and biofilm production were assessed in 135 clinical isolates from
87 patients. Gram-negative bacteria were the most represented microorganisms
(60.8%) with MDROs accounting for 31.8% of the total isolates. Assessment of
biofilm production revealed that 80% of the strains were able to form biofilm. A
comparable level of biofilm production was found with both MDRO and not-MDRO with
no significant differences between groups. All the methicillin-resistant
Staphylococcus aureus (MRSA) and 80% of Pseudomonas aeruginosa MDR strains were
found as moderate/high biofilm producers. Conversely, less than 17% of Klebsiella
pneumoniae extended-spectrum beta-lactamase (ESBL), Escherichia coli-ESBL and
Acinetobacter baumannii were moderate/high biofilm producers. Notably, those
strains classified as non-biofilm producers, were always associated with biofilm
producer bacteria in polymicrobial colonization. This study shows that biofilm
producers were present in all chronic skin ulcers, suggesting that biofilm
represents a key virulence determinant in promoting bacterial persistence and
chronicity of ulcerative lesions independently from the MDRO phenotype.
PMID- 28513579
TI - Electricity from methane by reversing methanogenesis.
AB - Given our vast methane reserves and the difficulty in transporting methane
without substantial leaks, the conversion of methane directly into electricity
would be beneficial. Microbial fuel cells harness electrical power from a wide
variety of substrates through biological means; however, the greenhouse gas
methane has not been used with much success previously as a substrate in
microbial fuel cells to generate electrical current. Here we construct a
synthetic consortium consisting of: (i) an engineered archaeal strain to produce
methyl-coenzyme M reductase from unculturable anaerobic methanotrophs for
capturing methane and secreting acetate; (ii) micro-organisms from methane
acclimated sludge (including Paracoccus denitrificans) to facilitate electron
transfer by providing electron shuttles (confirmed by replacing the sludge with
humic acids), and (iii) Geobacter sulfurreducens to produce electrons from
acetate, to create a microbial fuel cell that converts methane directly into
significant electrical current. Notably, this methane microbial fuel cell
operates at high Coulombic efficiency.
PMID- 28513580
TI - Global perturbation of organic carbon cycling by river damming.
AB - The damming of rivers represents one of the most far-reaching human modifications
of the flows of water and associated matter from land to sea. Dam reservoirs are
hotspots of sediment accumulation, primary productivity (P) and carbon
mineralization (R) along the river continuum. Here we show that for the period
1970-2030, global carbon mineralization in reservoirs exceeds carbon fixation
(PT, p.(T143M) and c.746C>T,
p.(P249L)) in ACPT, the gene encoding acid phosphatase, testicular, which
segregates with hypoplastic amelogenesis imperfecta in two unrelated families.
ACPT is reported to play a role in odontoblast differentiation and mineralisation
by supplying phosphate during dentine formation. Analysis by computerised
tomography and scanning electron microscopy of a primary molar tooth from an
individual homozygous for the c.746C>T variant revealed an enamel layer that was
hypoplastic, but mineralised with prismatic architecture. These findings
implicate variants in ACPT as a cause of early failure of amelogenesis during the
secretory phase.
PMID- 28513614
TI - Recurrent somatic JAK-STAT pathway variants within a RUNX1-mutated pedigree.
AB - Germline variants within the transcription factor RUNX1 are associated with
familial platelet disorder and acute leukemia in over 40% of carriers. At
present, the somatic events triggering leukemic transformation appear
heterogeneous and profiles of leukemia initiation across family members are
poorly defined. We report a new RUNX1 family where three sisters harboring a
germline nonsense RUNX1 variant, c.601C>T (p.(Arg201*)), developed acute
myelomonocytic leukemia (AML) at 5 years of age. Whole-exome sequencing of tumor
samples revealed all three siblings independently acquired variants within the
JAK-STAT pathway, specifically targeting JAK2 and SH2B3 (a negative regulator of
JAK2), while also sharing the 46/1 haplotype linked with sporadic JAK2-positive
myeloproliferative neoplasms. In-depth chromosomal characterization of tumors
revealed acquired copy number gains and uniparental disomy amplifying RUNX1, JAK2
and SH2B3 variants, highlighting the significance of co-operation between these
disrupted pathways. One sibling, presenting with myelodysplasia at 14 years, had
no evidence of clonal or subclonal JAK2 or SH2B3 variants, suggesting the latter
were specifically associated with leukemic transformation in her sisters.
Collectively, the clinical and molecular homogeneity across these three young
siblings provides the first notable example of convergent AML evolution in a
RUNX1 pedigree, with the recurrent acquisition of JAK-STAT pathway variants
giving rise to high-risk AML, characterized by chemotherapy resistance and
relapse.
PMID- 28513616
TI - Complementarity between medical geneticists and genetic counsellors: its added
value in genetic services in Europe.
AB - Clinical genetic services have progressed significantly the last few decades.
This has led to the need for non-medical health-care professionals working as
genetic counsellors in Europe and worldwide. However, there is no unified
approach to genetic counsellors' role in health-care services in Europe, as in
most countries the profession is still emerging and the educational backgrounds
diverge noticeably, within and between countries. This qualitative study aims to
describe the potential added value of genetic counsellors in clinical genetics
teams and to explore their tasks and responsibilities in different European
countries. A total of 143 participants providing genetic counselling in Europe at
the time of the survey responded. The results show differences in activities of
genetic counsellors, although there is a wide range of roles, which are similar.
The ability to establish a quality relationship with consultands was frequently
mentioned as one of the strengths of genetic counsellors, as well as a patient
centred approach. It is believed that genetic counsellors add a more holistic
approach of psychosocial and familial dimensions of genetic concerns to the
multidisciplinary teams. This study provides examples of successful integration
of genetic counsellors in teams, as complementariness with medical geneticist
became clear in several cases. Although the added value of genetic counsellors
was manifested, professional recognition of genetic counsellors across Europe is
still needed in order to support the quality of patients care and safety of
practice.
PMID- 28513615
TI - Exome sequencing of two Italian pedigrees with non-isolated Chiari malformation
type I reveals candidate genes for cranio-facial development.
AB - Chiari malformation type I (CMI) is a congenital abnormality of the cranio
cerebral junction with an estimated incidence of 1 in 1280. CMI is characterized
by underdevelopment of the occipital bone and posterior fossa (PF) and consequent
cerebellar tonsil herniation. The presence for a genetic basis to CMI is
supported by many lines of evidence. The cellular and molecular mechanisms
leading to CM1 are poorly understood. The occipital bone formation is dependent
on complex interactions between genes and molecules with pathologies resulting
from disruption of this delicate process. Whole-exome sequencing of affected and
not affected individuals from two Italian families with non-isolated CMI was
undertaken. Single-nucleotide and short insertion-deletion variants were
prioritized using KGGSeq knowledge-based platform. We identified three
heterozygous missense variants: DKK1 c.121G>A (p.(A41T)) in the first family, and
the LRP4 c.2552C>G (p.(T851R)) and BMP1 c.941G>A (p.(R314H)) in the second
family. The variants were located at highly conserved residues, segregated with
the disease, but they were not observed in 100 unaffected in-house controls. DKK1
encodes for a potent soluble WNT inhibitor that binds to LRP5 and LRP6, and is
itself regulated by bone morphogenetic proteins (BMPs). DKK1 is required for
embryonic head development and patterning. LRP4 is a novel osteoblast expressed
receptor for DKK1 and a WNT and BMP 4 pathways integrator. Screening of DKK1 in a
cohort of 65 CMI sporadic patients identified another missense variant, the
c.359G>T (p.(R120L)), in two unrelated patients. These findings implicated the
WNT signaling in the correct development of the cranial mesenchyme originating
the PF.
PMID- 28513618
TI - Age Increases Monocyte Adhesion on Collagen.
AB - Adhesion of monocytes to micro-injuries on arterial walls is an important early
step in the occurrence and development of degenerative atherosclerotic lesions.
At these injuries, collagen is exposed to the blood stream. We are interested
whether age influences monocyte adhesion to collagen under flow, and hence
influences the susceptibility to arteriosclerotic lesions. Therefore, we studied
adhesion and rolling of human peripheral blood monocytes from old and young
individuals on collagen type I coated surface under shear flow. We find that firm
adhesion of monocytes to collagen type I is elevated in old individuals. Pre
stimulation by lipopolysaccharide increases the firm adhesion of monocytes
homogeneously in older individuals, but heterogeneously in young individuals.
Blocking integrin alphax showed that adhesion of monocytes to collagen type I is
specific to the main collagen binding integrin alphaxbeta2. Surprisingly, we find
no significant age-dependent difference in gene expression of integrin alphax or
integrin beta2. However, if all integrins are activated from the outside, no
differences exist between the age groups. Altered integrin activation therefore
causes the increased adhesion. Our results show that the basal increase in
integrin activation in monocytes from old individuals increases monocyte adhesion
to collagen and therefore the risk for arteriosclerotic plaques.
PMID- 28513619
TI - Corrigendum: A brain-sparing diphtheria toxin for chemical genetic ablation of
peripheral cell lineages.
PMID- 28513617
TI - The perceived impact of the European registration system for genetic counsellors
and nurses.
AB - The aim of the European Board of Medical Genetics has been to develop and promote
academic and professional standards necessary in order to provide competent
genetic counselling services. The aim of this study was to explore the impact of
the European registration system for genetic nurses and counsellors from the
perspectives of those professionals who have registered. Registration system was
launched in 2013. A cross-sectional, online survey was used to explore the
motivations and experiences of those applying for, and the effect of registration
on their career. Fifty-five Genetic Nurses and Counsellors are registered till
now, from them, thirty-three agreed to participate on this study. The main
motivations for registering were for recognition of their work value and
competence (30.3%); due to the absence of a registration system in their own
country (15.2%) and the possibility of obtaining a European/international
certification (27.3%), while 27.3% of respondents registered to support
recognition of the genetic counselling profession. Some participants valued the
registration process as an educational activity in its own right, while the
majority indicated the greatest impact of the registration process was on their
clinical practice. The results confirm that registrants value the opportunity to
both confirm their own competence and advance the genetic counselling profession
in Europe.
PMID- 28513620
TI - Efficient hydrogen production on MoNi4 electrocatalysts with fast water
dissociation kinetics.
AB - Various platinum-free electrocatalysts have been explored for hydrogen evolution
reaction in acidic solutions. However, in economical water-alkali electrolysers,
sluggish water dissociation kinetics (Volmer step) on platinum-free
electrocatalysts results in poor hydrogen-production activities. Here we report a
MoNi4 electrocatalyst supported by MoO2 cuboids on nickel foam (MoNi4/MoO2@Ni),
which is constructed by controlling the outward diffusion of nickel atoms on
annealing precursor NiMoO4 cuboids on nickel foam. Experimental and theoretical
results confirm that a rapid Tafel-step-decided hydrogen evolution proceeds on
MoNi4 electrocatalyst. As a result, the MoNi4 electrocatalyst exhibits zero onset
overpotential, an overpotential of 15 mV at 10 mA cm-2 and a low Tafel slope of
30 mV per decade in 1 M potassium hydroxide electrolyte, which are comparable to
the results for platinum and superior to those for state-of-the-art platinum-free
electrocatalysts. Benefiting from its scalable preparation and stability, the
MoNi4 electrocatalyst is promising for practical water-alkali electrolysers.
PMID- 28513623
TI - Prevalence of malnutrition in a cohort of 509 patients with acute hip fracture:
the importance of a comprehensive assessment.
AB - : Backgrounds/objectives:Malnutrition is very common in acute hip fracture (HF)
patients. Studies differ widely in their findings, with reported prevalences
between 31 and 88% mainly because of small sample sizes and the use of different
criteria. The aim of this study was to learn the prevalence of malnutrition in a
large cohort of HF patients in an comprehensive way that includes the frequency
of protein-energy malnutrition, vitamin D deficiency and sarcopenia.
SUBJECTS/METHODS: A 1-year consecutive sample of patients admitted with fragility
HF in a 1300-bed public University Hospital, who were assessed within the first
72 h of admission. Clinical, functional, cognitive and laboratory variables were
included. Energy malnutrition (body mass index (BMI) <22 kg/m2), protein
malnutrition (serum total protein <6.5 g/dl or albumin <3.5 g/dl), vitamin D
deficiency (serum 25-OH-vitamin D <30 ng/dl) and sarcopenia (low muscle mass plus
low grip strength) were considered. RESULTS: Five hundred nine HF patients were
included. The mean age was 85.6+/-6.9 years and 79.2% were women. Ninety-nine
(20.1%) patients had a BMI <22 kg/m2. Four hundred nine patients (81.2%) had
protein malnutrition. Eighty-seven (17.1%) patients had both energy and protein
malnutrition. Serum vitamin D was <30 ng/ml in 466 (93%) patients. The prevalence
of sarcopenia was 17.1%. CONCLUSIONS: Protein malnutrition and vitamin D
deficiency are the rule in acute HF patients. Energy malnutrition and sarcopenia
are also common. A nutritional assessment in these patients should include these
aspects together.
PMID- 28513621
TI - Body mass index and mortality in lung cancer patients: a systematic review and
meta-analysis.
AB - Studies examining the relation of body mass index (BMI) and mortality in patients
with lung cancer have shown diverse results. We conducted a meta-analysis to
investigate the association using all available studies from January 1982 to
October 2016. PubMed and EMBASE were searched to identify relevant studies. We
calculated the summary hazard ratio (HR) and 95% confidence interval (CI) using
random effects model. The dose-response relationship was assessed by random
effects meta-regression model. Fifty-five articles from 51 studies involving 3
152 552 subjects (males, 54.8%) were included. The pooled results suggested that
on average a high BMI decreased risk of death from lung cancer or all-cause. Each
5 kg/m2 increase in BMI had a 12% lower risk of lung cancer-specific mortality
(HR=0.88, 95% CI: 0.75-1.02, P=0.09) and a 14% lower risk of all-cause mortality
(HR=0.86, 95% CI: 0.77-0.96, P<0.01). When stratifying by ethnicity, each 5 kg/m2
increase in BMI was associated with 22% and 28% reduction, respectively, in the
risk of lung cancer-specific mortality (P<0.01) and all-cause mortality (P<0.01)
in Asians, but no association was found in Westerners (P=0.51 and P=0.53,
respectively). In conclusion, lung cancer patients with a higher BMI have a
longer survival than those with a lower BMI. Considering the significant
heterogeneity between included studies, future studies are needed to confirm
these findings.
PMID- 28513622
TI - Human milk insulin is related to maternal plasma insulin and BMI: but other
components of human milk do not differ by BMI.
AB - BACKGROUND/OBJECTIVES: The impact of maternal BMI and insulin sensitivity on
bioactive components of human milk (HM) is not well understood. As the prevalence
of obesity and diabetes rises, it is increasingly critical that we understand how
maternal BMI and hormones associated with metabolic disease relate to
concentrations of bioactive components in HM. SUBJECTS/METHODS: This longitudinal
cohort design followed 48 breastfeeding mothers through the first four months of
lactation, collecting fasting morning HM samples at 2-weeks and 1, 2, 3 and 4
months, and fasting maternal blood at 2-weeks and 4-months. Insulin, glucose,
adipokines leptin and adiponectin, appetite regulating hormone ghrelin, marker of
oxidative stress 8OHdG and inflammatory cytokines (IL-6, IL-8, and TNF-a) were
measured in HM and maternal plasma. RESULTS: A total of 26 normal weight (NW)
(BMI=21.4+/-2.0 kg/m2) and 22 overweight/obese (OW/Ob) (BMI=30.4+/-4.2 kg/m2)
were followed. Of all HM analytes measured, only insulin and leptin were
different between groups - consistently higher in the OW/Ob group (leptin:
P<0.001; insulin: P<0.03). HM insulin was 98% higher than maternal plasma insulin
at 2-weeks and 32% higher at 4-months (P<0.001). Maternal fasting plasma insulin
and HOMA-IR were positively related to HM insulin at 2-weeks (P<0.001, R2?0.38,
n=31), and 4-months (P?0.005, R2?0.20, n=38). CONCLUSIONS: The concentrations of
insulin in HM are higher than in maternal plasma and are related to maternal BMI
and insulin sensitivity. With the exception of leptin, there were minimal other
differences observed in HM composition across a wide range in maternal BMI.
PMID- 28513624
TI - Type 2 diabetes mellitus in Malaysia: current trends and risk factors.
AB - This review discussed the prevalence of diabetes mellitus (DM) in Malaysia and
the associated major risk factors, namely overweight/obesity, dietary practices
and physical activity in both adults and school children. Detailed analyses of
such information will provide crucial information for the formulation and
implementation of programmes for the control and prevention of T2DM in the
country. National studies from 1996-2015, and other recent nation-wide studies
were referred to. The current prevalence of DM in 2015 is 17.5%, over double
since 1996. Females, older age group, Indians, and urban residents had the
highest risk of DM. The combined prevalence of overweight/obesity in 2015 is
47.7% for adults. Adults did not achieve the recommended intakes for majority of
the foods groups in the Malaysian Food Pyramid especially fruits and vegetables.
Adults also had moderate physical activity level. Three nation-wide studies
showed a prevalence ranging from 27 to 31% for combined overweight/obesity in
school children. The prevalence was higher among boys, primary school age, Indian
ethnicity, and even rural children are not spared. Physical activity level was
also low among school children. There must be serious systematic implementation
of action plans to combat the high prevalence of diabetes and associated risk
factors.
PMID- 28513625
TI - Diagnostic criteria for diabetes in China: are we pushing too much beyond
evidence?
PMID- 28513630
TI - IBD: Tofacitinib effective in ulcerative colitis.
PMID- 28513627
TI - Neuromorphic device architectures with global connectivity through electrolyte
gating.
AB - Information processing in the brain takes place in a network of neurons that are
connected with each other by an immense number of synapses. At the same time,
neurons are immersed in a common electrochemical environment, and global
parameters such as concentrations of various hormones regulate the overall
network function. This computational paradigm of global regulation, also known as
homeoplasticity, has important implications in the overall behaviour of large
neural ensembles and is barely addressed in neuromorphic device architectures.
Here, we demonstrate the global control of an array of organic devices based on
poly(3,4ethylenedioxythiophene):poly(styrene sulf) that are immersed in an
electrolyte, a behaviour that resembles homeoplasticity phenomena of the neural
environment. We use this effect to produce behaviour that is reminiscent of the
coupling between local activity and global oscillations in the biological neural
networks. We further show that the electrolyte establishes complex connections
between individual devices, and leverage these connections to implement
coincidence detection. These results demonstrate that electrolyte gating offers
significant advantages for the realization of networks of neuromorphic devices of
higher complexity and with minimal hardwired connectivity.
PMID- 28513626
TI - Fabrication of cerebral aneurysm simulator with a desktop 3D printer.
AB - Now, more and more patients are suffering cerebral aneurysm. However, long
training time limits the rapid growth of cerebrovascular neurosurgeons. Here we
developed a novel cerebral aneurysm simulator which can be better represented the
dynamic bulging process of cerebral aneurysm The proposed simulator features the
integration of a hollow elastic vascular model, a skull model and a brain model,
which can be affordably fabricated at the clinic (Fab@Clinic), under $25.00 each
with the help of a low-cost desktop 3D printer. Moreover, the clinical blood flow
and pulsation pressure similar to the human can be well simulated, which can be
used to train the neurosurgical residents how to clip aneurysms more effectively.
PMID- 28513628
TI - An integrated model for detecting significant chromatin interactions from high
resolution Hi-C data.
AB - Here we present HiC-DC, a principled method to estimate the statistical
significance (P values) of chromatin interactions from Hi-C experiments. HiC-DC
uses hurdle negative binomial regression account for systematic sources of
variation in Hi-C read counts-for example, distance-dependent random polymer
ligation and GC content and mappability bias-and model zero inflation and
overdispersion. Applied to high-resolution Hi-C data in a lymphoblastoid cell
line, HiC-DC detects significant interactions at the sub-topologically
associating domain level, identifying potential structural and regulatory
interactions supported by CTCF binding sites, DNase accessibility, and/or active
histone marks. CTCF-associated interactions are most strongly enriched in the
middle genomic distance range (~700 kb-1.5 Mb), while interactions involving
actively marked DNase accessible elements are enriched both at short (<500 kb)
and longer (>1.5 Mb) genomic distances. There is a striking enrichment of longer
range interactions connecting replication-dependent histone genes on chromosome
6, potentially representing the chromatin architecture at the histone locus body.
PMID- 28513631
TI - Paediatrics: Are human milk oligosaccharides the magic bullet for necrotizing
enterocolitis?
PMID- 28513629
TI - Post-infectious IBS, tropical sprue and small intestinal bacterial overgrowth:
the missing link.
AB - Evidence is emerging that IBS, a hitherto enigmatic disorder thought to be
predominantly related to psychological factors, has a microorganic basis in a
subset of patients with the disease. Post-infectious IBS (PI-IBS), commonly of
the diarrhoea-predominant subtype (defined as new development of IBS following
acute infectious diarrhoea), is one such condition known to occur in up to 10-30%
individuals after acute gastroenteritis. However, following acute infectious
gastroenteritis, patients can also develop post-infectious malabsorption syndrome
(PI-MAS), popularly known as tropical sprue. As no study on PI-IBS has rigorously
excluded tropical sprue by appropriate investigations, including small intestinal
biopsy, the frequency of tropical sprue among patients with PI-IBS is not known.
Small intestinal bacterial overgrowth (SIBO) has been suggested to be associated
with IBS in general, and in particular diarrhoea-predominant IBS, including PI
IBS. SIBO is also known to be associated with tropical sprue. As both IBS,
particularly the subset probably associated with SIBO, and tropical sprue improve
with antibiotic treatment, we provide evidence and an explanatory model to
support a link among these disorders.
PMID- 28513633
TI - NAFLD: A gut microbiome signature for advanced fibrosis diagnosis in NAFLD.
PMID- 28513634
TI - Mitochondria-targeted platinum(ii) complexes: dual inhibitory activities on tumor
cell proliferation and migration/invasion via intracellular trafficking of beta
catenin.
AB - Mitochondria-targeted therapy is an alternative strategy for cancer therapy and
may overcome the problems of metastasis and drug resistance that usually occur in
conventional treatment. In this work, we demonstrate the mitochondria-targeted
delivery of a cationic cyclometalated platinum(ii) complex, PIP-platin, in cancer
cells. PIP-platin showed selective delivery and accumulation in the mitochondria
and exhibited toxicity against a variety of tumor cell lines. The mitochondria
were disrupted by PIP-platin, along with the generation of reactive oxygen
species, depolarization of mitochondrial membrane potential, release of
cytochrome c and necrosis. Interestingly, PIP-platin can promote cell adhesion
within several hours and the cells became hard to dislodge from the culture
plate. A wound healing assay, transwell migration/invasion assay and 3D spheroid
migration assay all demonstrated that PIP-platin can inhibit cell
migration/invasion. To illustrate the associated mechanisms, we investigated the
intracellular trafficking of beta-catenin, a central protein in the regulation of
cell adhesion, and gene transcription for cell proliferation. Upon treatment with
PIP-platin, this protein can translocate onto the plasma membrane for increased
cell adhesion. In addition, PIP-platin was demonstrated to efficiently inhibit
Wnt signaling by blocking the translocation of beta-catenin into the nuclei,
thereby preventing cell proliferation. We demonstrate that, accordingly, PIP
platin has remarkable potential for intracellular delivery in mitochondria and
has inhibitory effects on cancer cell proliferation and migration/invasion
through beta-catenin, and may therefore be exploited as a dual-functional
antitumor drug candidate in cancer treatment.
PMID- 28513635
TI - The impact of dark chocolate intake on arterial elasticity in individuals with
HIV/AIDS undergoing ART: a randomized, double-blind, crossover trial.
AB - An increase in the frequency of cardiovascular diseases has been observed in the
HIV/AIDS population. Studies involving healthy subjects or subjects with other
diseases have shown benefits of chocolate supplementation on endothelial function
and vasodilation. We evaluate the impact of chocolate consumption on arterial
elasticity in people living with human immunodeficiency virus - PLHIV. A double
blind, crossover trial including 110 PLHIV (19 to 59 years) on antiretroviral
therapy - ART for at least 6 months and with a viral load of <500 copies per mL
was conducted. All subjects were randomly assigned to 15-d dietary supplements
containing dark chocolate or placebo with a 15-d washout period. Each participant
received one of the two sequences: A (dark chocolate, placebo chocolate); B
(placebo chocolate, dark chocolate). Arterial elasticity was measured using the
HDI/PulseWaveTM CR-2000 CardioVascular Profiling System(r). Body composition,
lipid profile, C-reactive protein, and thiobarbituric acid reactive substances
were also assessed. Analysis of variance (ANOVA) for repeated measures using the
Stata 11.0(r) program was used for cross-over analysis. Most subjects were men
(59.0%) and Caucasian (46.1%) and the mean age was 44.6 +/- 7.1 years. The mean
time since diagnosis of HIV infection was 13.7 +/- 5.3 years and the mean
duration of ART was 12.9 +/- 4.2 years. Chocolate consumption resulted in
significant alterations in the large artery elasticity index - LAEI (p = 0.049)
and the mean concentration of HDL-c was higher after supplementation with dark
chocolate (p = 0.045). This is the first study to evaluate the effect of
chocolate on arterial elasticity in PLHIV. The results showed that dark chocolate
consumption for 15 days improved the elastic properties of the LAEI in PLHIV.
These findings, added to the noninvasive method used, may expand the knowledge of
CVDs in this population.
PMID- 28513636
TI - Modular synthesis of self-assembling Janus-dendrimers and facile preparation of
drug-loaded dendrimersomes.
AB - Materials and methods aimed at the next generation of nanoscale carriers for
drugs and other therapeutics are currently in great demand. Yet, creating these
precise molecular arrangements in a feasible and straightforward manner
represents a remarkable challenge. Herein we report a modular synthetic route for
amphiphilic Janus-dendrimers via a copper-catalyzed click reaction (CuAAC) and a
facile procedure, using simple injection, to obtain highly uniform dendrimersomes
with efficient loading of the model drug compound propranolol. The resulting
assemblies were analyzed by dynamic light scattering and cryogenic transmission
electron microscopy revealing the formation of unilamellar and multilamellar
dendrimersomes. The formation of a bilayer structure was confirmed using cryo-TEM
and confocal microscopy visualization of an encapsulated solvatochromic dye (Nile
Red). The dendrimersomes reported here are tunable in size, stable over time and
display robust thermal stability in aqueous media. Our results expand the scope
of dendrimer-based supramolecular colloidal systems and offer the means for one
step fabrication of drug-loaded dendrimersomes in the size range of 90-200 nm,
ideal for biomedical applications.
PMID- 28513632
TI - How to stomach an epigenetic insult: the gastric cancer epigenome.
AB - Gastric cancer is a deadly malignancy afflicting close to a million people
worldwide. Patient survival is poor and largely due to late diagnosis and
suboptimal therapies. Disease heterogeneity is a substantial obstacle,
underscoring the need for precision treatment strategies. Studies have identified
different subgroups of gastric cancer displaying not just genetic, but also
distinct epigenetic hallmarks. Accumulating evidence suggests that epigenetic
abnormalities in gastric cancer are not mere bystander events, but rather promote
carcinogenesis through active mechanisms. Epigenetic aberrations, induced by
pathogens such as Helicobacter pylori, are an early component of gastric
carcinogenesis, probably preceding genetic abnormalities. This Review summarizes
our current understanding of the gastric cancer epigenome, highlighting key
advances in recent years in both tumours and pre-malignant lesions, made possible
through targeted and genome-wide technologies. We focus on studies related to DNA
methylation and histone modifications, linking these findings to potential
therapeutic opportunities. Lessons learned from the gastric cancer epigenome
might also prove relevant for other gastrointestinal cancers.
PMID- 28513637
TI - The synergy between atomically dispersed Pd and cerium oxide for enhanced
catalytic properties.
AB - We report a photochemical synthesis of Pd/CeO2 catalysts with atomically
dispersed Pd. Compared to atomically dispersed Pd/CeO2 with a cubic CeO2 support
(Pd/CeO2-CP), atomically dispersed Pd/CeO2 with a truncated octahedral CeO2
support (Pd/CeO2-TOP) exhibited higher activity and selectivity, owing to the
synergy between Pd atoms and the (111) surface of CeO2. When compared to Pd/CeO2
with Pd clusters and nanoparticles via chemical reduction, Pd/CeO2-TOP showed
excellent activity with an enhancement factor of 324 in CO oxidation, as well as
an activity enhancement by a factor of 344 in selective oxidation of benzyl
alcohol.
PMID- 28513638
TI - Automatic assignment of metal-containing peptides in proteomic LC-MS and MS/MS
data sets.
AB - Transition metal-containing proteins and enzymes are critical for the maintenance
of cellular function and metal-based (metallo)drugs are commonly used for the
treatment of many diseases, such as cancer. Detection and characterisation of
metallodrug targets is crucial for improving drug-design and therapeutic
efficacy. Due to the unique isotopic ratios of many metal species, and the
complexity of proteomic samples, standard MS data analysis of these species is
unsuitable for accurate assignment. Herein a new method for differentiating metal
containing species within complex LCMS data is presented based upon the Smart
Numerical Annotation Procedure (SNAP). SNAP-LC accounts for the change in
isotopic envelopes for analytes containing non-standard species, such as metals,
and will accurately identify, record, and display the particular spectra within
extended LCMS runs that contain target species, and produce accurate lists of
matched peaks, greatly assisting the identification and assignment of modified
species and tailored to the metals of interest. Analysis of metallated species
obtained from tryptic digests of common blood proteins after reactions with three
candidate metallodrugs is presented as proof-of-concept examples and demonstrates
the effectiveness of SNAP-LC for the fast and accurate elucidation of metallodrug
targets.
PMID- 28513639
TI - Strong enhancement of electrical conductivity in two-dimensional micrometer-sized
RuO2 nanosheets for flexible transparent electrodes.
AB - The enhancement in electrical transport properties of exfoliated individual RuO2
NSs was systemically investigated for their application in flexible electronics
and optoelectronics. Decoration of Ag NPs on the surface of the RuO2 NSs provides
donor electrons and dramatically increases the electrical conductivity of the
monolayer RuO2 NSs by up to 3700%. The n-type doping behavior was confirmed via
Hall measurement analysis of the doped RuO2 NSs. The layer number- and
temperature-dependence of the conductivity were also investigated. Moreover,
carrier concentration and mobility were obtained from Hall measurements,
indicating that the undoped RuO2 NSs had ambipolar transport and semi-metallic
characteristics. Moreover, the Ag-doped RuO2 NS multilayer films on polycarbonate
substrates were demonstrated by the Langmuir-Blodgett assembly methods, showing
one-third reduction in the sheet resistance and extraordinarily high bending
stability that the change in the resistance was less than 1% over 50 000 cycles.
PMID- 28513644
TI - Light induced cytotoxicity of nitrofurantoin toward murine melanoma.
AB - The cytotoxicity of nitrofurantoin (NFT) in the dark and after light exposure
(UVA irradiation, lambda = 385 nm) was evaluated in murine melanoma B16F10 cells.
NFT induces both cell proliferation and inhibition of cell viability. The
dominance of one or the other effect depends on the drug concentration,
incubation time (tinc) and irradiation dose. The uptake of NFT in these cells, as
well as its photocytotoxicity, reaches saturation after 24 hours of incubation.
The mechanism of cell death in the dark is associated with the enzymatic release
of nitric oxide (NO). The increase of NFT cytotoxicity under light irradiation is
associated with the increase of NO concentration due to photorelease. NO
photorelease by NFT in solution was confirmed by chemiluminescence, while NO
formation in cells was confirmed by fluorescence microscopy using DAF-2DA, a
specific indicator of NO in living cells. The NFT does not enter nuclei,
distributing preferentially in the cell cytoplasm, as shown by fluorescence
microscopy.
PMID- 28513645
TI - Electrode potential dependent desolvation and resolvation of germanium(100) in
contact with aqueous perchlorate electrolytes.
AB - The electrode potential dependence of the hydration layer on an n-Ge(100) surface
was studied by a combination of in situ and operando electrochemical attenuated
total reflection infrared (ATR-IR) spectroscopy and real space density functional
theory (DFT) calculations. Constant-potential DFT calculations were coupled to a
modified generalised Poisson-Boltzmann ion distribution model and applied within
an ab initio molecular dynamics (AIMD) scheme. As a result, potential-dependent
vibrational spectra of surface species and surface water were obtained, both
experimentally and by simulations. The experimental spectra show increasing
absorbance from the Ge-H stretching modes at negative potentials, which is
associated with an increased negative difference absorbance of water-related OH
modes. When the termination transition of germanium from OH to H termination
occurs, the surface switches from hydrophilic to hydrophobic. This transition is
fully reversible. During the switching, the interface water molecules are
displaced from the surface forming a "hydrophobic gap". The gap thickness was
experimentally estimated by a continuum electrodynamic model to be ~2 A. The
calculations showed a shift in the centre of mass of the interface water by ~0.9
A due to the surface transformation. The resulting IR spectra of the interfacial
water in contact with the hydrophobic Ge-H show an increased absorbance of free
OH groups, and a decreased absorbance of strongly hydrogen bound water.
Consequently, the surface transformation to a Ge-H terminated surface leads to a
surface which is weakening the H-bond network of the interfacial water in
contact.
PMID- 28513646
TI - Biocompatibility and therapeutic evaluation of magnetic liposomes designed for
self-controlled cancer hyperthermia and chemotherapy.
AB - Magnetic liposome-mediated combined chemotherapy and hyperthermia is gaining
importance as an effective therapeutic modality for cancer. However, control and
maintenance of optimum hyperthermia are major challenges in clinical settings due
to the overheating of tissues. To overcome this problem, we developed a novel
magnetic liposomes formulation co-entrapping a dextran coated biphasic suspension
of La0.75Sr0.25MnO3 (LSMO) and iron oxide (Fe3O4) nanoparticles for self
controlled hyperthermia and chemotherapy. However, the general apprehension about
biocompatibility and safety of the newly developed formulation needs to be
addressed. In this work, in vitro and in vivo biocompatibility and therapeutic
evaluation studies of the novel magnetic liposomes are reported. Biocompatibility
study of the magnetic liposomes formulation was carried out to evaluate the signs
of preliminary systemic toxicity, if any, following intravenous administration of
the magnetic liposomes in Swiss mice. Therapeutic efficacy of the magnetic
liposomes formulation was evaluated in the fibrosarcoma tumour bearing mouse
model. Fibrosarcoma tumour-bearing mice were subjected to hyperthermia following
intratumoral injection of single or double doses of the magnetic liposomes with
or without chemotherapeutic drug paclitaxel. Hyperthermia (three spurts, each at
3 days interval) with drug loaded magnetic liposomes following single dose
administration reduced the growth of tumours by 2.5 fold (mean tumour volume 2356
+/- 550 mm3) whereas the double dose treatment reduced the tumour growth by 3.6
fold (mean tumour volume 1045 +/- 440 mm3) compared to their corresponding
control (mean tumour volume 3782 +/- 515 mm3). At the end of the tumour efficacy
studies, the presence of MNPs was studied in the remnant tumour tissues and vital
organs of the mice. No significant leaching or drainage of the magnetic liposomes
during the study was observed from the tumour site to the other vital organs of
the body, suggesting again the potential of the novel magnetic liposomes
formulation for possibility of developing as an effective modality for treatment
of drug resistant or physiologically vulnerable cancer.
PMID- 28513647
TI - IF5 affects the final stage of the Cl-F exchange fluorination in the synthesis of
pentafluoro-lambda6-sulfanyl-pyridines, pyrimidines and benzenes with electron
withdrawing substituents.
AB - A difficult chlorine-fluorine (Cl-F) exchange fluorination reaction in the final
stage of the preparation of pentafluoro-lambda6-sulfanyl-(hetero)arenes having
electron-withdrawing substituents has now been elucidated through the use of
iodine pentafluoride. A major side-reaction of C-S bond cleavage was sufficiently
inhibited by the potential interaction between F and I with a halogen bonding.
PMID- 28513649
TI - Recent advances in the chemical transformations of functionalized
alkylidenecyclopropanes (FACPs).
AB - During the past several years, functionalized alkylidenecyclopropanes (FACPs)
have attracted intensive attention in synthetic chemistry. Many interesting
transformations of FACPs have been developed to synthesize a lot of structurally
diverse and valuable polycyclic and heterocyclic compounds. This review will
classify FACPs into aryl-FACPs, alkyl-FACPs and ring-FACPs for the first time,
and recent interesting chemical transformations in these research fields will be
included, respectively, from 2011. Moreover, we will pay more attention to the
clarification of the reaction mechanism, in which the C-C bond cleavage of
alkylidenecyclopropanes (ACPs) will be emphasized.
PMID- 28513648
TI - Radical-carbene coupling reaction: Mn-catalyzed synthesis of indoles from
aromatic amines and diazo compounds.
AB - An unprecedented coupling reaction between aromatic amines and diazo compounds
was well developed, which afforded a bridge connecting between radical chemistry
and metal carbene chemistry. This Mn-catalyzed tandem reaction also provided a
fundamentally different and practical approach to the indole skeleton under mild
conditions.
PMID- 28513650
TI - Photo-induced copper-catalyzed C-H chalcogenation of azoles at room temperature.
AB - Inexpensive copper catalysts enabled direct C-H chalcogenations at ambient
temperature by means of photo-induced catalysis. The expedient copper catalysis
set the stage for C-S and C-Se bond formation from readily accessible non
volatile elemental chalcogens. The photo-assisted copper catalysis manifold
proved suitable for a wide range of substrates with good functional group
tolerance and exhibited high catalytic efficacy even at a reaction temperature of
25 degrees C.
PMID- 28513651
TI - A tripeptide-based self-shrinking hydrogel for waste-water treatment: removal of
toxic organic dyes and lead (Pb2+) ions.
AB - A triphenylalanine-based superhydrogel shows automatic syneresis (self
compressing properties) with time and this self-shrinking behavior has been
successfully utilized to remove toxic lead ions and organic dyes from waste-water
efficiently with the ability to re-use for a few times.
PMID- 28513652
TI - An electrochemiluminescence assay for sensitive detection of methyltransferase
activity in different cancer cells by hybridization chain reaction coupled with a
G-quadruplex/hemin DNAzyme biosensing strategy.
AB - In this work, a highly sensitive electrochemiluminescence (ECL) assay was
fabricated for the detection of human DNA (cytosine-5)-methyltransferase1 (DNMT1)
activity in cancer cells. The ECL assay coupled hybridization chain reaction with
a G-quadruplex/hemin DNAzyme biosensing strategy. The ECL intensity changes
(DeltaI) allowed detection of DNMT1 activity down to 0.09 U mL-1, and DeltaI was
proportional to the logarithm of the activity of DNMT1 within the range of 1.0 to
30.0 U mL-1 in buffer solution. It also showed high sensitivity to DNMT1 activity
in A549 cells, with a detection limit of about 2 cells. This ECL assay provides a
promising platform for profiling of the mutational cells of tumors and shows a
great potential for application to DNA methylation-related clinical diagnostics.
PMID- 28513653
TI - 3D and 2D supramolecular assemblies and thermotropic behaviour of a carbo
benzenic mesogen.
AB - Hexaalkoxy-di(phenylethynyl)-tetraphenyl-carbo-benzenes bearing six CnH2n+1
aliphatic chains (n = 12, 18) have been synthesized and characterized, including
by single crystal XRD analysis. For n = 12, a liquid crystal behaviour was
observed in the range of 109-130 degrees C. DSC, POM and PXRD analyses evidenced
a rectangular columnar mesophase at 115 degrees C. The determined 3D lattice
constants are consistent with 2D STM images of the so-called "carbo-mesogen"
deposited on an HOPG surface.
PMID- 28513654
TI - Rhodium-catalyzed synthesis of 1,2-dihydropyridine by a tandem reaction of 4-(1
acetoxyallyl)-1-sulfonyl-1,2,3-triazole.
AB - A tandem reaction of 4-(1-acetoxyallyl)-1-sulfonyl-1,2,3-triazole including
formation of alpha-imino rhodium carbene, 1,2-migration of an acetoxy group and
six electron electrocyclic ring closure was reported. The migration of the OAc
group with excellent chemoselectivity was the crucial process, leading to the
formation of 1,2-dihydropyridine specifically in up to 90% yield. Several
transformations of the dihydropyridine product were also achieved illustrating
the potential of the protocol in organic synthesis. Based on the observation of
the intermediate, a plausible mechanism was proposed.
PMID- 28513655
TI - Boron difluoride hemicurcuminoid as an efficient far red to near-infrared
emitter: toward OLEDs and laser dyes.
AB - A hemicurcuminoid boron difluoride complex is used as an emitter in organic light
emitting diodes, showing far red/near-infrared electroluminescence with an
external quantum efficiency as high as 2.1%. This dye blended in CBP thin films
shows amplified spontaneous emission with a threshold of 22 MUJ cm-2 at 750 nm,
making this compound attractive for organic semiconductor lasers operating in the
near-infrared region.
PMID- 28513657
TI - Copper-catalyzed hydroallylation of allenes employing hydrosilanes and allyl
chlorides.
AB - The hydroallylation of allenes was developed by employing a hydrosilane and allyl
chlorides in the presence of a copper catalyst. The reaction provided (E)-1,5
dienes mainly in good to high yields.
PMID- 28513656
TI - Restoring the biophysical properties of decellularized patches through
recellularization.
AB - Various extracellular matrix (ECM) scaffolds, isolated through decellularization,
were suggested as ideal biomimetic materials for 'Functional tissue engineering'
(FTE). The decellularization process comprises a compromise between damaging and
preserving the ultrastructure and composition of ECM-previously shown to affect
cell survival, proliferation, migration, organization, differentiation and
maturation. Inversely, the effects of cells on the ECM constructs' biophysical
properties, under physiological-like conditions, remain still largely unknown. We
hypothesized that by re-cellularizing porcine cardiac ECM (pcECM, as a model
scaffold) some of the original biophysical properties of the myocardial tissue
can be restored, which are related to the scaffold's surface and the bulk
modifications consequent to cellularization. We performed a systematic
biophysical assessment of pcECM scaffolds seeded with human mesenchymal stem
cells (MSCs), a common multipotent cell source in cardiac regenerative medicine.
We report a new type of FTE study in which cell interactions with a composite
scaffold were evaluated from the perspective of their contribution to the
biophysical properties of the construct surface (FTIR, WETSEMTM) and bulk (DSC,
TGA, and mechanical testing). The results obtained were compared with acellular
pcECM and native ventricular tissue serving as negative and positive controls,
respectively. MSC recellularization resulted in an inter-fiber plasticization
effect, increased protein density, masking of acylated glycosaminoglycans (GAGs)
and active pcECM remodelling which further stabilized the reseeded construct and
increased its denaturation resistance. The systematic approach presented herein,
therefore, identifies cells as "biological plasticizers" and yields important
methodologies, understanding, and data serving both as a reference as well as
possible 'design criteria' for future studies in FTE.
PMID- 28513658
TI - Capillary zone electrophoresis-mass spectrometry with microliter-scale loading
capacity, 140 min separation window and high peak capacity for bottom-up
proteomics.
AB - Better peptide separation is required for bottom-up proteomics for further
improving the proteome coverage. The two-dimensional liquid chromatography (2D
LC) systems only explore differences among peptides in their hydrophobicity
(reversed-phase, RP) and charge (strong cation/anion exchange, SCX/SAX).
Alternative separation techniques with different separation mechanisms are
required to further improve the separation. Capillary zone electrophoresis (CZE)
is an attractive alternative because it has high efficiency for separation of
biomolecules and it separates analytes based on their size-to-charge ratios,
complementary with LC. However, the low loading capacity and narrow separation
window of CZE limit its wide application for large-scale proteomics. In this
manuscript, we present an automated CZE-mass spectrometry (MS) system for solving
those issues. The CZE-MS system can approach at least half-a-microliter loading
capacity with good robustness and reproducibility, can routinely use over 12% of
the available sample in the sample vial for analysis, and can generate a 140 min
separation window and high peak capacity (~380) for complex proteome analysis.
The results represent the highest peak capacity and the widest separation window
of CZE for peptide separation with a microliter-scale loading capacity. It is the
first time that CZE-MS approaches both the microliter-scale loading capacity and
over 2-hour separation window for analysis of complex samples. The automated CZE
MS system dramatically reduces the gap between CZE-MS and RPLC-MS in terms of
loading capacity, separation window and peak capacity. It truly opens the door
for large-scale bottom-up proteomics using CZE-MS.
PMID- 28513660
TI - Access to dihydropyridinones and spirooxindoles: application of N-heterocyclic
carbene-catalyzed [3+3] annulation of enals and oxindole-derived enals with 2
aminoacrylates.
AB - A strategy for the NHC-catalyzed synthesis of dihydropyridinones and
spirooxindoles has been developed via [3+3] annulation reactions of enals or
isatin-derived enals with 2-aminoacrylates under oxidative conditions. In this
efficient strategy, the 2-aminoacrylates served as nucleophiles. Modifying the
standard base switched the carbon-carbon double bond formation from 5,6-positions
to 3,4-positions to generate 5,6-dihydropyridinones and 3,4-dihydropyridinones,
respectively. Meanwhile, a diverse set of spirooxindole derivatives were also
synthesized in good to excellent yields.
PMID- 28513659
TI - Serum-resistant, reactive oxygen species (ROS)-potentiated gene delivery in
cancer cells mediated by fluorinated, diselenide-crosslinked polyplexes.
AB - The transfection performance of polycations is often hampered by various systemic
barriers that pose conflicting requirements for material design. Herein, we
developed fluorinated, ROS-cleavable polyethylenimine (PEI) for effective and
serum-resistant gene delivery to cancer cells, by harmonizing the inconsistency
between DNA condensation and release, and the inconsistency between cellular
internalization and serum stability. Low-molecular weight (MW) PEI was cross
linked with a diselenide-containing linker and further modified with fluorocarbon
chains. The obtained high-MW DSe-PEI-F has potent DNA condensation as well as
intracellular DNA delivery capabilities, while in the cytoplasm of cancer cells,
it can rapidly degrade into low-MW segments upon ROS treatment to promote DNA
release and reduce the material toxicity. As such, DSe-PEI-F showed high
transfection efficiencies in cancer cells in the presence of serum, outperforming
the commercial reagent PEI 25k by several orders of magnitude. This study thus
provides an effective approach to overcome various barriers against non-viral
gene delivery, which contributes to the development of a new class of gene
vectors with high efficiency and low toxicity.
PMID- 28513661
TI - A zwitterionic hydrocarbon-soluble borenium ion based on a beta-diketiminate
backbone.
AB - A versatile synthetic route has been developed to access strongly Lewis acidic
borenium cations (and heavier group 13 analogues) featuring a pendant weakly
coordinating borate function. The hydrocarbon-soluble borenium/borate zwitterion
is more strongly Lewis acidic than B(C6F5)3, despite featuring a pendant (non
fluorinated) aryl group and two flanking N-donors.
PMID- 28513662
TI - Chemical synthesis of dual labeled proteins via differently protected alkynes
enables intramolecular FRET analysis.
AB - We report a novel method for multisite protein conjugation by setting differently
silyl-protected alkynes as conjugation handles, which can remain intact through
the whole synthetic procedure and provide sequential and orthogonal conjugation.
This strategy enables efficient preparation of a dual dye-labeled protein and
structural analysis via an intramolecular FRET mechanism.
PMID- 28513663
TI - Reductive activation of O2 by a bioinspired Fe complex for catalytic epoxidation
reactions.
AB - Aerobic epoxidation of olefins catalyzed by iron complexes without the use of a
sacrificial coreductant is unknown. We report the reductive activation of O2 by a
bioinspired [(bTAML)FeIII(H2O)]- (1) complex to catalyze the epoxidation of
alkenes with TONs of up to 80. Spectroscopic and kinetic evidence indicates the
involvement of FeV(O) as the active oxidant during the reaction.
PMID- 28513664
TI - A resilient and luminescent stimuli-responsive hydrogel from a heterotopic 1,8
naphthalimide-derived ligand.
AB - A heterotopic naphthalimide ligand N-(4-picolyl)-4-(4'-carboxyphenoxy)-1,8
naphthalimide HL is utilised for the formation of self-assembled soft materials.
In the presence of K+ ions, L- forms a robust photoluminescent hydrogel 1 which
is reversible under thermal, mechanical or chemical stimuli.
PMID- 28513665
TI - A fully integrated microchip system for automated forensic short tandem repeat
analysis.
AB - We have successfully developed an integrated microsystem that combines two
plastic microchips for DNA extraction and PCR amplification with a glass
capillary array electrophoresis chip together in a compact control and detection
instrument for automated forensic short tandem repeat (STR) analysis. DNA
extraction followed by an "in situ PCR" was conducted in a single reaction
chamber of the microchip based on a filter paper-based extraction methodology.
PCR products were then mixed with sizing standards by an injection electrode and
injected into the electrophoresis chip for four-color confocal fluorescence
detection. The entire STR analysis can be completed in about two hours without
any human intervention. Since the 15-plex STR system has a more stringent
requirement for PCR efficiency, we optimized the structure of the plastic DNA
extraction and amplification chip, in which the reaction chamber was formed by
sandwiching a hollow structure layer with two blank cover layers, to reduce the
adsorption of PCR reagents to the surfaces. In addition, PCR additives, bovine
serum albumin, poly(ethylene glycol), and more magnesium chloride were included
into the on-chip multiplex STR system. The limit-of-detection study demonstrated
that our microsystem was able to produce full 15-plex STR profiles from 3.75 ng
standard K562 DNA. Buccal swab and whole blood samples were also successfully
typed by our system, validating the feasibility of performing rapid DNA typing in
a "sample-in-answer-out" manner for on-site forensic human identification.
PMID- 28513666
TI - High performance solution-processable tetrathienoacene (TTAR) based small
molecules for organic field effect transistors (OFETs).
AB - Three new organic semiconductors with alkyl chain-substituted tetrathienoacene
(TTAR) as the central core and both ends capped with thiophene (DT-TTAR),
thienothiophene (DTT-TTAR) and dithienothiophene (DDTT-TTAR) have been
synthesized and characterized for organic field effect transistor (OFET)
applications. A hole mobility of 0.81 cm2 V-1 s-1 was achieved for the DDTT-TTAR
film, which represents the highest mobility yet found for a solution-processable
p-type TTAR-based small molecular semiconductors.
PMID- 28513667
TI - Hierarchical self-supported ZnAlEu LDH nanotubes hosting luminescent CdTe quantum
dots.
AB - Self-supported oligo-layered ZnAlEu LDH nanotubes (? 20 nm) self-assemble upon
controlled hydrolysis of the metal ions (Zn2+, Al3+, Eu3+) in the presence of
1,3,5-benzenetricarboxylate anions and non-ionic worm-like micelles. Their high
surface area and easily accessible cylindrical mesopores (175 m2 g-1; 0.75 cm3 g
1) facilitate interaction with 5 nm CdTe quantum dots, enhancing the overall
luminescence behavior.
PMID- 28513668
TI - Computational analysis of site differences in selective aliphatic C-H
hydroxylation by nonheme iron-oxo complexes.
AB - Selective C-H hydroxylation by nonheme iron complexes offers a promising method
in the field of organic synthesis. Aliphatic C-H bond oxidation reactions of
pivalate (R) catalyzed by [Fe(S,S-PDP)(CH3CN)2]2+ (CAT1) were examined using the
density functional theory. Our calculations of the CH3CN solvent agree with the
experimental findings. However, it was observed that the gas-phase results did
not replicate selective C-H hydroxylation observed experimentally when CAT1
catalyzed hydrocarbon oxidations by H2O2via an HO-FeV[double bond, length as m
dash]O oxidant (CAT1a). We inferred that the difference was mainly from hydrogen
bonding formation, (CAT1a) O-HO[double bond, length as m-dash]C (R), in certain
gaseous H-abstraction transition states (TSH). Then, the appearance of the
stronger (CAT1a) O-HN[triple bond, length as m-dash]CCH3-solvent weakened the
aforementioned interaction, leading to C-H activation influenced primarily by
their electronic and steric properties. Such a deduction explained the same
selective C-H found in both phases of reactions with CAT1b, a cyclic ferric
peracetate oxidant, by the reason of TSH without the influence of H-bonding.
Another interesting finding was that the commonly recognized radical intermediate
was further isomerized by a favorable electron rearrangement. Thus, the
subsequent OH-rebound behavior proceeded by an electrostatic interaction. This
study provides mechanistic clues for modifying regioselective C-H hydroxylation
for molecule synthesis applications.
PMID- 28513670
TI - Effects of the asphaltene structure and the tetralin/heptane solvent ratio on the
size and shape of asphaltene aggregates.
AB - Asphaltene molecules, which consist of differently hydrogenated polyaromatic
cores grafted with side alkyl chains of different sizes and grafting densities,
were simulated with a solvent mixture of heptane and tetralin using coarse
grained force fields. Starting with the initial configuration of randomly
distributed asphaltene molecules and solvents, the asphaltene molecules aggregate
because of the attractive force between their polyaromatic cores, but their sizes
and shapes differ. The average aggregate size decreases with an increase in the
hydrogenated polycyclic core, side-chain length, and tetralin concentration,
which agree with experimental observations in the hydrocracking process. The
number of side chains also influences the aggregate size but only in the presence
of tetralin. In particular, the effect of tetralin addition occurs more
significantly for asphaltene molecules with more side chains because side chains
sterically block the intermolecular interactions between polyaromatic cores,
which makes it easier for the aromatic ring of tetralin to bind to the
polyaromatic core of asphaltene. These steric effects of side chains yield
different shapes of aggregates, showing parallel stacking (face-to-face) for
aromatic cores with many side chains, and T-shape (edge-to-face) or offset
parallel stacking for those with fewer side chains. These findings agree with the
experimental observation regarding the effect of tetralin on the solubility of
asphaltene, and indicate that the extent of the tetralin effect depends on the
number of side alkyl chains, implying that tetralin solvents need to be added
with consideration for the structural change of asphaltene under hydrogenation or
dealkylation conditions.
PMID- 28513669
TI - The open-cubane oxo-oxyl coupling mechanism dominates photosynthetic oxygen
evolution: a comprehensive DFT investigation on O-O bond formation in the S4
state.
AB - The dioxygen formation mechanism of biological water oxidation in nature has long
been the focus of argument; many diverse mechanistic hypotheses have been
proposed. Based on a recent breakthrough in the resolution of the electronic and
structural properties of the oxygen-evolving complex in the S3 state, our density
functional theory (DFT) calculations reveal that the open-cubane oxo-oxyl
coupling mechanism, whose substrates preferably originate from W2 and O5 in the
S2 state, emerges as the best candidate for O-O bond formation in the S4 state.
This is justified by the overwhelming energetic superiority of this mechanism
over alternative mechanisms in both the isomeric open and closed-cubane forms of
the Mn4CaO5 cluster; spin-dependent reactivity rooted in variable magnetic
couplings was found to play an essential role. Importantly, this oxygen evolution
mechanism is supported by the recent discovery of femtosecond X-ray free electron
lasers (XFEL), and the origin of the observed structural changes from the S1 to
S3 state has been analyzed. In this view, we corroborate the proposed water
binding mechanism during S2-S3 transition and correlate the theoretical models
with experimental findings from aspects of substrate selectivity according to
water exchange kinetics. This theoretical consequence for native metalloenzymes
may serve as a significant guide for improving the design and synthesis of
biomimetic materials in the field of photocatalytic water splitting.
PMID- 28513671
TI - Temporal analysis of blister evolution during anion intercalation in graphite.
AB - In the currently accepted picture, when graphite is immersed and polarized in a
diluted sulfuric acid electrolyte, the surface undergoes an invasive process due
to the intercalation of solvated sulphate anions inside the crystal. The
following evolution of CO, CO2 and O2 promotes the surface swelling and the
growth of blisters. Here, we give evidence that the appearance of blisters
affects the graphite surface as soon as the oxygen potential is reached, i.e.
before the traditionally accepted anion intercalation stage, which instead is
demonstrated slowing the blister development. These results suggest a new picture
of the solvated anion intercalation in graphite with respect to the current
interpretative model.
PMID- 28513672
TI - A computational study of the electronic properties, ionic conduction, and thermal
expansion of Sm1-xAxCoO3 and Sm1-xAxCoO3-x/2 (A = Ba2+, Ca2+, Sr2+, and x = 0.25,
0.5) as intermediate temperature SOFC cathodes.
AB - The substitutional doping of Ca2+, Sr2+, and Ba2+ on the Sm-site in the cubic
perovskite SmCoO3 is reported to improve both electronic and ionic conductivities
for applications as solid oxide fuel cell (SOFC) cathodes. Hence, in this study
we have used density functional theory (DFT) calculations to investigate dopant
configurations at two different dopant concentrations: 25 and 50%. To preserve
the electroneutrality of the system, we have studied two different charge
compensation mechanisms: the creation of oxygen vacancies, and electronic holes.
After examining the electronic structure, charge density difference, and oxygen
vacancy formation energies, we concluded that oxygen vacancy charge compensation
is the preferred mechanism to maintain the electroneutrality of the system.
Furthermore, we found that the improvement of the electronic conduction is not a
direct consequence of the appearance of electron holes, but a result of the
distortion of the material, more specifically, the distortion of the Co-O bonds.
Finally, molecular dynamics were employed to model ionic conduction and thermal
expansion coefficients. It was found that all dopants at both concentrations
showed high ionic conduction comparable to experimental results.
PMID- 28513673
TI - Stability, electronic structure, and optical properties of protected gold-doped
silver Ag29-xAux (x = 0-5) nanoclusters.
AB - In this work, we used density functional theory (DFT) and linear response time
dependent DFT (LR-TDDFT) to investigate the stability, electronic structure, and
optical properties of Au-doped [Ag29-xAux(BDT)12(TPP)4]3- nanoclusters (BDT: 1,3
benzenedithiol; TPP triphenylphosphine) with x = 0-5. The aim of this work is to
shed light on the most favorable doped structures by comparing our results with
previously published experimental data. The calculated relative energies, ranging
between 0.8 and 10 meV per atom, indicate that several doped Ag29-xAux
nanoclusters are likely to co-exist at room temperature. However, only the Au
doped [Ag29-xAux(BDT)12(TPP)4]3- nanoclusters that have direct bonding between Au
dopants and phosphines display an enhancement in the electronic transitions at
~450 nm. This agrees with the main spectral absorption features that have been
experimentally reported for the mixture of Au-doped silver Ag29-xAux
nanoclusters. In addition, the formation of the Au-TPP bond could prevent cluster
degradation starting from the detachment of the phosphine molecules, since the Au
TPP bond is stronger by ~0.4 eV than the analogous Ag-TPP one. Thus, the results
presented here show the important role of Au-TPP bonding in determining the
stability and optical properties of thiolate/phosphine-protected Ag29-xAux
nanoclusters.
PMID- 28513674
TI - Molecular organization in the twist-bend nematic phase by resonant X-ray
scattering at the Se K-edge and by SAXS, WAXS and GIXRD.
AB - Using a magnetically aligned liquid crystal mixture containing a novel Se
labelled dimer and the difluoroterphenyl dimer DTC5C7, the twist-bend nematic
phase (Ntb) was studied by the resonant scattering of hard X-rays and by
conventional small and wide-angle X-ray scattering (SAXS, WAXS). Resonant
diffraction spots indicated a helix with a 9-12 nm pitch in the Ntb phase and an
unprecedentedly high helix orientation. This enabled deconvolution of global and
local order parameters. These findings, combined with the simultaneously recorded
resonant and non-resonant SAXS and WAXS data, allowed us to construct a locally
layered molecular model of the Ntb phase, where the average twisted conformation
of each molecule was idealised as a helical segment, matching the local
heliconical director field. The dimers were found to be less bent in the Ntb
phase than in their minimum energy conformation, and straightening further with
increasing temperature. It is proposed that on further heating their low bend
angle allows the transition to the normal nematic phase, where the molecules can
freely move longitudinally, without the need to perform screw-like motion as in
the Ntb phase. At the low-temperature end, the increasing molecular twist becomes
unsustainable, leading to a transition to a smectic phase, where no twist is
required.
PMID- 28513675
TI - Photophysical properties and the NO photorelease mechanism of a ruthenium
nitrosyl model complex investigated using the CASSCF-in-DFT embedding approach.
AB - A complete state-averaged active space self-consistent field (SA-CASSCF)
calculation by means of the SA-CASSCF(18,14)-in-BP86 Miller-Manby embedding
approach was performed to explore the ground and excited electronic states of the
trans-[RuCl(NO)(NH3)4]2+ complex. Insights into the NO photodissociation
mechanism and Ru-NO bonding properties are provided. In addition, spin-orbit (SO)
interactions were taken into account to describe and characterize the spin
forbidden transitions observed at the low-energy regions of the trans
[RuCl(NO)(NH3)4]2+ UV-Vis spectrum. The SA-CASSCF(18,14)-in-BP86 electronic
spectrum is in great agreement with the experimental data of Schreiner [Schreiner
et al., Inorg. Chem., 1972, 11, 880].
PMID- 28513676
TI - Intermediate phases during solid to liquid transitions in long-chain n-alkanes.
AB - The solid to liquid phase transition of n-alkanes with more than ten carbon atoms
is an interesting phenomenon relevant to many fields, from cosmetics to
automotive. Here we report Raman spectroscopy of tetradecane, pentadecane and
hexadecane as a function of temperature. In order to gain information on the
structural changes that the hydrocarbons undergo during melting, and to determine
the temperature and the speed at which the phase change occurs, their temperature
dependent Raman spectra are acquired. The spectra are analysed not only with
respect to frequency shifts, band widths, and intensity ratio of certain bands,
but also using a principal component analysis. The spectroscopic data suggest
that the solid to liquid phase transition in hexadecane, differently from
tetradecane and pentadecane, is almost instantaneous. Tetradecane shows a
slightly faster transition than pentadecane. In addition, a rotator phase as an
intermediate state between the liquid and crystalline solid phases is identified
in pentadecane. Different characteristic features in the solid spectra of the
hydrocarbons relate tetradecane and hexadecane to a tryclinic crystalline
structure, and pentadecane to an orthorhombic structure.
PMID- 28513677
TI - Regular and red-shifted fluorescence of the donor-acceptor compound 5-(1H-pyrrole
1-yl)thiophenecarbonitrile (TCN) is efficiently quenched by internal modes of
thiophene.
AB - The photochemical properties of thiophene analogs of N-pyrrolobenzonitrile (PBN),
notably the two isomers 5-(1H-pyrrole-1-yl)thiophene-2-carbonitrile (2-TCN) and 5
(1H-pyrrole-1-yl)thiophene-3-carbonitrile (3-TCN) have been investigated. The aim
of this study is to reveal whether the donor-acceptor compound TCN shows a
fluorescence behavior similar to other benzonitrile derivatives like PBN and N,N
dimethylaminobenzonitrile (DMABN). For this purpose high-level ab initio methods
have been employed comprising approximate coupled cluster (CC2) methods, the
algebraic-diagramatic construction scheme for the polarization propagator (ADC(2)
and ADC(3)) as well as time-dependent density functional theory (TDDFT). Solvent
effects have been included using continuum solvation models. In the gas phase
excited TCN molecules most likely deactivate in a radiationless fashion to the
ground state via a low lying S1/S0 conical intersection. In polar solvents the
dark S(CT) (S2) state is stabilized below S(pipi*) (S1), however, despite this
stabilization radiationless decay to the ground state remains the most likely
deactivation pathway. Nevertheless, population of a twisted minimum of the S(CT)
state becomes energetically feasible. Hence it is predicted that TCN does not
show any fluorescence in the gas phase, and if at all only weak red-shifted
emission from a twisted intramolecular charge transfer (TICT) minimum may be
observable in polar solvents.
PMID- 28513678
TI - Mechanochemically induced sulfur doping in ZnO via oxygen vacancy formation.
AB - Surface defects of ZnO nanoparticles were induced via mechanical stressing using
a Turbula shaker mixer and a planetary ball mill, and the possibilities for
surface modification and functionalization of the ZnO nanoparticles were
exemplified by sulfur doping of activated ZnO. Raman spectroscopy reveals that
the formation of oxygen vacancies (VO) does not only occur under high stressing
conditions in a planetary ball mill but even upon rather 'mild stressing' in the
shaker mixer. The temporal evolution of the vacancy concentration in ZnO stressed
under different conditions can be described by a model that accounts for stress
number and vacancy diffusion with diffusion coefficients of VO of 3.7 * 10-21 m2
s-1 and 2.4 * 10-20 m2 s-1 for stressing in the shaker and the planetary ball
mill, respectively. The thickness of the VO layer was estimated to be about 1 nm.
Thiourea was mixed with defective ZnO particles, and then heated at various
temperatures for sulfur-doping. A linear relationship between the amount of
induced VO and the level of sulfur doping was found. Remarkably, mechanical
activation is indispensable in order to control the level of sulfur doping
quantitatively. High-angle annular dark field scanning transmission electron
microscopy (HAADF STEM) observations with energy dispersive X-ray spectroscopy
(EDX) analysis clearly revealed that the doped sulfur atoms are concentrated at
the particle surface. Thus, ZnO (core)/ZnS (shell) structures are obtained easily
via mechanochemical activation and subsequent thermal treatment.
PMID- 28513679
TI - A novel synthesis of an Fe3+/Fe2+ layered double hydroxide ('green rust') via
controlled electron transfer with a conducting polymer.
AB - This report examines the influence of a conducting polymer on the crystal growth
of labile green rust (GR) through hybridization with polypyrrole. All hybrids
used in this study were prepared via one-pot co-precipitation at neutral pH, with
specific stoichiometric ratios among all chemical species. The role of the
conducting polymer and the effective stoichiometric ratio were demonstrated to
facilitate the crystal growth of GR.
PMID- 28513680
TI - Molecular structures of various alkyldichlorosilanes in the solid state.
AB - A series of organodichlorosilanes RR'SiCl2 (R,R' = (CH2)3; (CH2)4; (CH2)5; Me,Me;
Me,H; Me,Cl) was studied by single-crystal X-ray diffraction analyses. At ambient
temperature liquid chlorosilanes (melting points in the range of 180-220 K) were
transferred into glass capillaries and crystallized in situ on a diffractometer.
In the solid state structure these chlorosilanes are monomeric, even in the case
of the sterically less demanding 1,1-dichlorosilacyclobutane (CH2)3SiCl2.
Interestingly, regardless the steric demand of the alkyl substituents, the
dialkyldichlorosilanes exhibit essentially the same Cl-Si-Cl angle (for
(CH2)3SiCl2, (CH2)4SiCl2, (CH2)5SiCl2, Me2SiCl2: 106.08(3) degrees , 106.07(4)
degrees /105.86(4) degrees , 106.91(2) degrees and 105.59(6) degrees ,
respectively). Replacement of one alkyl group by hydrogen has only a marginal
influence on the Cl-Si-Cl angle (MeHSiCl2 106.31(3) degrees ), whereas in MeSiCl3
slightly wider Cl-Si-Cl angles are found (ranging between 107.04(11) degrees and
107.86(11) degrees ), in accordance with VSEPR. Computational analyses, i.e.,
potential energy surface scans of the Cl-Si-Cl angle variation, of (CH2)3SiCl2,
Me2SiCl2, MeHSiCl2 and H2SiCl2 reveal essentially identical energy profiles for
the Cl-Si-Cl deformation in these four dichlorosilanes with basically
superimposed curves for (CH2)3SiCl2 and Me2SiCl2, whereas with increasing H
substitution the energetic minimum is shifted to a slightly wider Cl-Si-Cl angle.
In the crystal packing only MeHSiCl2 exhibits weak intermolecular SiCl van der
Waals contacts, whereas the Si-Cl moieties of the other five chlorosilanes engage
in intermolecular ClH and (for (CH2)3SiCl2, (CH2)4SiCl2 and MeSiCl3) ClCl
contacts.
PMID- 28513681
TI - Heteroleptic iron(iii) Schiff base spin crossover complexes: halogen
substitution, solvent loss and crystallite size effects.
AB - The influence of the halogen substituent on the qsal moiety of iron(iii)
heteroleptic compounds with the formulae [Fe(qsal-X)(thsa)].nMeCN, where qsal-X-
= X-substituted quinolylsalicylaldimine; thsa2- = thiosemicarbazone
salicylaldiminate; X = F; n = 2.5, 1.2.5MeCN and X = Cl 2, Br 3 and I 4, n = 1
(labelled 2.MeCN, 3.MeCN and 4.MeCN, respectively) has been systematically
investigated. Magnetic studies on solid samples show incomplete spin crossover in
1-3 which can be related to MeCN solvent loss. Complex 4.MeCN remains fully LS up
to 360 K. Single crystals have been examined at variable temperatures for samples
possessing different degrees of solvation. Intermolecular C-XH interactions are
present for X = F, Cl and Br while a C-Ipi interaction is uniquely observed in
4.MeCN. These preferential interactions result in different supramolecular
packings of the various halogen substituted compounds. However, as the LS
stability increases from F to I, the ligand field strength is then also suggested
to increase from F to I. Consequently, in this family, the electronic structure
resulting from halogen variation is believed to influence the magnetic properties
more than crystal packing effects. Mossbauer spectra, at variable temperatures,
confirm the presence of Fe(iii) and the magnetic properties in these compounds.
The effect of different drying methods as well as the crystal/powder effect on
the magnetic properties are discussed in the case of 2.MeCN.
PMID- 28513684
TI - Ultrafast IR spectroscopy of photo-induced electron transfer in self-assembled
donor-acceptor coordination cages.
AB - Photo-induced processes in self-assembled coordination cages were studied by
femtosecond infrared pump-probe spectroscopy. Densely packed, interpenetrated
double cages were constructed from eight bis-monodentate redoxactive ligands
bound to four Pd(ii) nodes. Two types of ligands consisting of electron rich
phenothiazine (PTZ) or electron deficient anthraquinone (ANQ) chromophores were
used to assemble either homo-octameric or mixed-ligand cages. Upon
photoexcitation the homo-octameric acceptor cage undergoes intersystem crossing
to a long-lived triplet state, similar to the free acceptor ligand. Excitation of
the free donor ligand leads to a fluorescent state with intramolecular charge
transfer character. This fluorescence is completely quenched in the homo
octameric donor double cage due to a ligand-to-metal charge transfer followed by
back electron transfer on a ps timescale. Only for the mixed-ligand cage
irradiation produces a charge separated state with an oxidized PTZ radical cation
and a reduced ANQ radical anion as proven by their vibrational fingerprints in
the transient IR spectra. In dichloromethane the lifetime of this charge
separated state extends from tens of ps to >1.5 ns which is attributed to the
broad distribution of mixed-ligand cages with different stoichiometry and/or
stereo configurations.
PMID- 28513683
TI - A theoretical study of low-lying singlet and triplet excited states of
quinazoline, quinoxaline and phthalazine: insight into triplet formation.
AB - Quinazoline, quinoxaline and phthalazine are nitrogen containing heterocyclic
aromatic molecules which belong to the class diazanaphthalenes. These isomers
have low-lying npi* and naphthalene-like pipi* states that interact via spin
orbit coupling. In this contribution, we study their structure and electronic
states by means of a coupled-cluster method. The computed properties are compared
to those of cinnoline which were obtained in our previous study [Etinski et al.,
Phys. Chem. Chem. Phys., 2014, 16, 4740]. The excited state features of these
isomers are dependent on the position of the nitrogen atoms. We find that
quinazoline and quinoxaline exhibit similarities in the ordering and character of
the excited states. In contrast, a marked difference in the electronic and
geometric structures of the lowest excited triplet states of cinnoline and
phthalazine is noticed, although both are orthodiazanaphthalenes. Our findings
suggest that the S1 [radiolysis arrow - arrow with voltage kink] T1 channel is
responsible for the rapid intersystem crossing in quinazoline and quinoxaline,
whereas the S1 [radiolysis arrow - arrow with voltage kink] T2 pathway is active
in phthalazine.
PMID- 28513687
TI - Modeling DNA oxidation in water.
AB - A novel set of hole-site energies and electronic coupling parameters to be used,
in the framework of the simplest tight-binding approximation, for predicting DNA
hole trapping efficiencies and rates of hole transport in oxidized DNA is
proposed. The novel parameters, significantly different from those previously
reported in the literature, have been inferred from reliable density functional
calculations, including both the sugar-phosphate ionic backbone and the effects
of the aqueous environment. It is shown that most of the experimental oxidation
free energies of DNA tracts and of oligonucleotides available from photoelectron
spectroscopy and voltammetric measurements are reproduced with great accuracy,
without the need for introducing sequence dependent parameters.
PMID- 28513686
TI - A tri-functional vanadium(iv) complex to detect cysteine oxidation.
AB - The development of effective molecular probes to detect and image the levels of
oxidative stress in cells remains a challenge. Herein we report the design,
synthesis and preliminary biological evaluation of a novel optical probe to
monitor oxidation of thiol groups in cysteine-based phosphatases (CBPs).
Following orthogonal protecting approaches we synthesised a new vanadyl complex
designed to bind to CBPs. This complex is functionalised with a well-known
dimedone derivative (to covalently trap sulfenic acids, SOHs) and a coumarin
based fluorophore for optical visualization. We show that this new probe
efficiently binds to a range of phosphatases in vitro with nanomolar affinity.
Moreover, preliminary flow cytometry and microscopy studies in live HCT116 cells
show that this probe can successfully image cellular levels of sulfenic acids -
one of the species resulting from protein oxidative damage.
PMID- 28513689
TI - Proton conduction in a hydrogen-bonded complex of copper(ii)-bipyridine
glycoluril nitrate.
AB - Bipyridine glycoluril (BPG), a urea-fused bipyridine tecton, forms a square
pyramidal secondary building unit with copper(ii) which further self-assembles to
give a porous hydrogen-bonded complex. This complex displays a high proton
conductivity of 4.45 * 10-3 S cm-1 at 90 degrees C and 95% relative humidity
(RH). Chains consisting of coordinated water, solvent water and nitrate anions
embedded in the complex are responsible for high proton conduction. The proton
conduction pathway was corroborated by ab initio electronic structure
calculations with molecular dynamics (MD) simulations using the Nudged Elastic
Band (NEB) method. The theoretical activation energy estimated to be 0.18 eV is
in close agreement with the experimental value of 0.15 eV which evidences a
Grotthuss proton hopping mechanism. We thus demonstrate that the hydrogen-bonded
complex encapsulating appropriate counter ions, coordinated water and solvent
water molecules exhibts superprotonic conductivity.
PMID- 28513688
TI - Solution-processed two-dimensional layered heterostructure thin-film with
optimized thermoelectric performance.
AB - Graphene-based two-dimensional (2D) heterostructures have ignited intensive
interest in recent years because of their excellent physical performance.
However, the most common method to prepare them uses chemical vapor deposition,
which has the drawback of a complex process unsuitable for large-scale
production. In this respect, reduced graphene oxide and transitional metal
dichalcogenides (rGO-TMDs) composite thin-films were fabricated by a simple
solution-processing method and their thermoelectric performance was investigated
systematically. Addition of rGO nanosheets (NSs) efficiently improved the
electrical conductivity of MoS2 and WS2 (MS2) NSs, due to the excellent electron
transport performance of rGO. Furthermore, it should be noted that an optimized
content of rGO can effectively avoid direct contact between TMDs NSs by forming a
rGO-TMDs heterojunction, leading to significantly increased electrical
conductivity and a slight variation in its Seebeck coefficient. Our work obtained
high thermoelectric performance heterostructures by inducing two kinds of layered
materials using a simple method that may potentially be applied to other 2D
layered materials to construct heterostructures for energy conversion.
PMID- 28513690
TI - Influence of the nature and environment of manganese in Mn-BEA zeolites on NO
conversion in selective catalytic reduction with ammonia.
AB - Manganese-containing BEA zeolites, MnxSiBEA (x = 1-4 wt%) and Mn(I.E.)AlBEA, were
prepared by a two-step post-synthesis method and a conventional wet ion-exchange,
respectively, and applied as catalysts in the selective catalytic reduction of NO
with ammonia (NH3-SCR). The physicochemical analysis of zeolite properties by
high-energy-resolution fluorescence-detected XANES (HERFD-XANES) and X-ray
emission spectroscopy (XES) uncovered that the coordination, geometry and
oxidation state of Mn species are strongly related to the preparation method.
Additionally, the study of catalyst acidity by FTIR spectroscopy with CO and
pyridine probe molecules provided important insight into the number and type of
acidic centres present on the catalyst surface. The catalytic results revealed
that NO conversion depended on the state and content of Mn. The zeolites obtained
by the two-step post-synthesis method and with a low Mn content were very active
in the medium temperature range (NO conversion ~100%) with simultaneous high
selectivity to N2 due to the presence of isolated, framework Mn(iii) and Mn(ii)
species. The N2O formation was especially high in the case of catalysts
containing extra-framework polynuclear Mn species and negligible in the case of
Mn(I.E.)AlBEA containing predominantly isolated, extra-framework Mn(ii) species.
PMID- 28513691
TI - Conformational behavior and stacking interactions of contorted polycyclic
aromatics.
AB - We present a systematic computational analysis of the conformations and stacking
interactions of a set of 18 saddle-shaped, contorted polycyclic aromatic
compounds at the B97-D3M(BJ)/TZV(2d,2p)//B97-D/TZV(2d,2p) level of theory. These
doubly-concave systems offer a means of tuning the strength of stacking
interactions through variations in molecular curvature, and understanding the
intermolecular non-covalent interactions exhibited by these systems will aid the
design of contorted polycyclic systems with precisely defined packing in the
solid state. Computations reveal wide variations in both the nature of the low
lying conformations and the stacking affinities of these systems. In particular,
the introduction of both thiophene rings around the periphery of these systems
and the incorporation of B and N atoms into the coronene core can greatly enhance
their tendency to form strongly stacked dimers. Overall, these data provide a
reminder that curvature does not always lead to stronger stacking interactions.
PMID- 28513692
TI - Odd-even effect in two dimensions induced by the bicomponent blends of isobutenyl
compounds.
AB - Scanning tunneling microscopy (STM) investigation was performed for the blends of
isobutenyl compounds, in which the long alkyl chains were connected with ester or
carbamoyl linkages. Each component by itself did not show the odd-even effect of
alkyl chain length, whereas after blending them, the 2D structures drastically
changed and modulated to exhibit odd-even effect. Star, lozenge, twist-like, and
linear structures were found, dependent on the blend ratio and alkyl chain
length. The blend ratio dependence of 2D structures was explained in terms of
homogeneous and heterogeneous dimerization due to the interdigitation of alkyl
chains.
PMID- 28513693
TI - Synthesis, characterization and in vitro and in vivo anticancer activity of
Pt(iv) derivatives of [Pt(1S,2S-DACH)(5,6-dimethyl-1,10-phenanthroline)].
AB - This report describes the synthesis, characterization and biological activity of
a series of platinum(iv) derivatives of [Pt(1S,2S-DACH)(5,6-dimethyl-1,10
phenanthroline)] (Pt56MeSS) with non-bioactive, lipophilic and bioactive axial
ligands. In an attempt to explore the anticancer activity potential of the Pt(iv)
derivatives, 2D and 3D cytotoxic screening and a preliminary in vivo study were
performed. The average IC50 values of the platinum(iv) derivatives ranged from
1.26 to 5.39 MUM, compared with 1.24 MUM for Pt56MeSS, suggesting that the axial
ligands have a relatively minor effect on the potency of the compounds.
Preliminary in vivo studies indicate that the platinum(iv) derivatives of
Pt56MeSS are active in vivo and can reduce the tumor to a similar extent to
cisplatin.
PMID- 28513694
TI - Atomic scale observation of a defect-mediated first-order phase transition in
VO2(A).
AB - The study of first-order structural transformations has attracted extensive
attention due to their significant scientific and industrial importance. However,
it remains challenging to exactly determine the nucleation sites at the very
beginning of the transformation. Here, we report the atomic scale real-time
observation of a unique defect-mediated reversible phase transition between the
low temperature phase (LTP) and the high temperature phase (HTP) of VO2(A). In
situ Cs-corrected scanning transmission electron microscopy (STEM) images clearly
indicate that both phase transitions (from the HTP to the LTP and from the LTP to
the HTP) start at the defect sites in parent phases. Intriguingly, the structure
of the defects within the LTP is demonstrated to be the HTP of VO2 (A), and the
defect in the HTP of VO2(A) is determined to be the LTP structure of VO2(A).
These findings are expected to broaden our current understanding of the first
order phase transition and shed light on controlling materials' structure
property phase transition by "engineering" defects in applications.
PMID- 28513695
TI - Surface passivation and self-regulated shell growth in selective area-grown GaN
(Al,Ga)N core-shell nanowires.
AB - The large surface-to-volume ratio of GaN nanowires implicates sensitivity of the
optical and electrical properties of the nanowires to their surroundings. The
implementation of an (Al,Ga)N shell with a larger band gap around the GaN
nanowire core is a promising geometry to seal the GaN surface. We investigate the
luminescence and structural properties of selective area-grown GaN-(Al,Ga)N core
shell nanowires grown on Si and diamond substrates. While the (Al,Ga)N shell
allows a suppression of yellow defect luminescence from the GaN core, an overall
intensity loss due to Si-related defects at the GaN/(Al,Ga)N interface has been
observed in the case of Si substrates. Scanning transmission electron microscopy
measurements indicate a superior crystal quality of the (Al,Ga)N shell along the
nanowire side facets compared to the (Al,Ga)N cap at the top facet. A nucleation
study of the (Al,Ga)N shell reveals a pronounced bowing of the nanowires along
the c-direction after a short deposition time which disappears for longer growth
times. This is assigned to an initially inhomogeneous shell nucleation. A
detailed study of the proceeding shell growth allows the formulation of a strain
driven self-regulating (Al,Ga)N shell nucleation model.
PMID- 28513696
TI - External electric field driving the ultra-low thermal conductivity of silicene.
AB - The manipulation of thermal transport is in increasing demand as heat transfer
plays a critical role in a wide range of practical applications, such as
efficient heat dissipation in nanoelectronics and heat conduction hindering in
solid-state thermoelectrics. It is well established that the thermal transport in
semiconductors and insulators (phonons) can be effectively modulated by structure
engineering or materials processing. However, almost all the existing approaches
involve altering the original atomic structure of materials, which would be
hindered due to either irreversible structure change or limited tunability of
thermal conductivity. Motivated by the inherent relationship between phonon
behavior and interatomic electrostatic interaction, we comprehensively
investigate the effect of external electric field, a widely used gating technique
in modern electronics, on the lattice thermal conductivity (kappa). Taking two
dimensional silicon (silicene) as a model, we demonstrate that by applying an
electric field (Ez = 0.5 V A-1) the kappa of silicene can be reduced to a record
low value of 0.091 W m-1 K-1, which is more than two orders of magnitude lower
than that without an electric field (19.21 W m-1 K-1) and is even comparable to
that of the best thermal insulation materials. Fundamental insights are gained
from observing the electronic structures. With an electric field applied, due to
the screened potential resulting from the redistributed charge density, the
interactions between silicon atoms are renormalized, leading to phonon
renormalization and the modulation of phonon anharmonicity through electron
phonon coupling. Our study paves the way for robustly tuning phonon transport in
materials without altering the atomic structure, and would have significant
impact on emerging applications, such as thermal management, nanoelectronics and
thermoelectrics.
PMID- 28513697
TI - Self-assembled nanohelix from a bolaamphiphilic diacetylene via hydrogelation and
selective responsiveness towards amino acids and nucleobases.
AB - A bolaamphiphile with diacteylene mesogen unit and l-glutamic acid as the
terminal group was newly designed and its self-assembly was investigated. The
compound formed hydrogels with water upon heating and cooling. The as-formed gel
could be switched to a dispersion upon mechanical shaking. Both the gel and the
water dispersion undergo polymerization upon UV irradiation. However, the gel
turned to blue and then purple red color, while the dispersion turned red
directly. Using AFM and SEM observations, it was found that nanohelix was formed
in the as-prepared gel and polymerized blue gels, while nanobelt was formed from
the water dispersion. The blue nanohelix was stable but showed selective response
to certain amino acids and nucleobases. It was found that the blue gel underwent
shrinkage when reacting with charged amino acids such as Glu, Asp, Lys, Arg and
His. In the shrunk gel, the solution phase further turned pink in the case of His
and Arg. In addition, the blue gel showed also shrinkage and color change when
reacting with cytosine.
PMID- 28513698
TI - Unzipping and shearing DNA with electrophoresed nanoparticles in hydrogels.
AB - We show electric control of unzipping and shearing dehybridization of a DNA
duplex anchored to a hydrogel. Tensile force is applied by electrophoresing (25 V
cm-1) gold nanoparticles pulling the DNA duplex. The pulled DNA strand is
gradually released from the hydrogel. The unzipping release rate is faster than
shearing; for example, 3-fold for a 15 base pair duplex, which helps to design
electrically driven DNA devices.
PMID- 28513700
TI - Outstanding reviewers for Lab on a Chip in 2016.
PMID- 28513699
TI - Multifunctional nanoprobes for both fluorescence and 19F magnetic resonance
imaging.
AB - Fluorescence is widely used for cell imaging due to its high sensitivity and rich
color choice but limited for in vivo imaging because of its low light
penetration. Meanwhile, magnetic resonance imaging (MRI) is widely applied for in
vivo diagnosis but not suitable for cell imaging because of its low resolution.
Compared to 1H-MRI, 19F-MRI is more suitable for clinical application due to its
high sensitivity but fabricating 19F-MRI probes is a great challenge. Therefore,
it is highly desirable to develop a dual-modal imaging probe for both cell
fluorescence imaging and in vivo19F-MRI with high sensitivity and deep
penetration. In this study, 19F moiety loaded nanocomposites with an organic
fluorescent core were successfully prepared via a facile strategy by
encapsulating organic dyes with oleylamine-functionalized polysuccinimide and
1H,1H,2H,2H-perfluorodecyltriethoxysilane (PDTES). The aggregation of organic
fluorescent dyes in the core results in significant fluorescence for optical
imaging, while the 19F moieties on PDTES allow for simultaneous 19F MRI.
Moreover, the nanocomposites exhibited high water dispersibility and excellent
biocompatibility. These properties make them promising for both cell imaging and
in vivo imaging applications.
PMID- 28513702
TI - Stretchable impedance sensor for mammalian cell proliferation measurements.
AB - This paper presents the fabrication and testing of a novel stretchable electric
cell-substrate impedance sensing (ECIS) lab on a chip device. This is the first
time that ECIS electrodes were fabricated on a stretchable polydimethylsiloxane
(PDMS) substrate and ECIS measurements were performed on mammalian cells exposed
to cyclic strain. The stretchable ECIS biosensors simulate in vitro the dynamic
environment of organisms, such as pulsation, bending and stretching, which
enables investigations on cell behavior that undergoes mechanical stimuli in
biological tissue. Usually cell-based assays used in cell mechanobiology rely on
endpoint cell tests, which provide a limited view on dynamic cellular mechanisms.
The ECIS technique is a label-free, real-time and noninvasive method to monitor
the cellular response to mechanical stimuli. Bovine aortic endothelial cells
(BAECs) have been used in this research because the BAECs are exposed in vivo to
cyclic physiologic elongation produced by blood circulation in the arteries.
These innovative stretchable ECIS biosensors were used to analyze the
proliferation of BAECs under different cyclic mechanical stimulations. The
results of fluorescence based cell proliferation assays confirmed that the
stretchable ECIS sensors were able to analyze in real-time the BAEC
proliferation. The novel stretchable ECIS sensor has the ability to analyse cell
proliferation, determine the cell number and density, and apply mechanical
stimulation at the same time.
PMID- 28513703
TI - Nonlinear photoluminescence in monolayer WS2: parabolic emission and excitation
fluence-dependent recombination dynamics.
AB - Recombination dynamics during photoluminescence (PL) in two-dimensional (2D)
semiconducting transition metal dichalcogenides (TMDs) are complicated and can be
easily affected by the surroundings because of their atomically thin structures.
Herein, we studied the excitation power and temperature dependence of the
recombination dynamics on the chemical vapor deposition-grown monolayer WS2via a
combination of Raman, PL, and time-resolved PL spectroscopies. We found a red
shift and parabolic intensity increase in the PL emission of the monolayer WS2
with the increasing excitation power and the decay time constants corresponding
to the recombination of trions and excitons from transient PL dynamics. We
attributed the abovementioned nonlinear changes in the PL peak positions and
intensities to the combination of increasing carrier interaction and band
structure renormalization rather than to the thermal effect from a laser.
Furthermore, the excitation power-dependent Raman measurements support our
conclusion. These findings and understanding will provide important information
for the development of TMD-based optoelectronics and photonics.
PMID- 28513704
TI - Modeling the formation of TiO2 ultra-small nanoparticles.
AB - The structures of TiO2 ultra-small nanoparticles (USNPs) at the atomistic level
have been predicted because of their potential importance in catalytic,
environmental, biological and energy applications. Low energy (TiO2)n clusters
and USNPs (n up to 80 at the B3LYP/DZVP2 level, and up to 384 at the PM6 level)
were found using a novel bottom-up global optimization approach that is based on
all-atom real-space calculations. These structures include USNPs that belong to 1
D, 2-D and 3-D USNP series where all the members share the same fragment types
and local translational symmetries. Most of the metastable 2-D and 3-D USNPs
contain tubular building blocks similar to the 1-D USNPs. The 3-D USNPs that
resemble the bulk anatase are predicted to be energetically favorable structures
for 64 <= n <= 384. A fragment-based model was developed to relate the energy
with geometry for the 1-D, 2-D and 3-D USNPs. Surface energy densities were
predicted for surface fragments at the different positions of the USNPs using
this new model. Based on the predicted surface energy densities and the partial
density of states, the most catalytically active sites for the anatase-like 3-D
USNPs were predicted to be the kink sites on Face-x surfaces consisting of an
octahedral-Ti, the step (edge) sites between the Face-x and Face-y surfaces
consisting of a square pyramidal-Ti (on Face-x), and the step sites consisting of
a trigonal bipyramidal Ti on the Face-y surfaces.
PMID- 28513705
TI - On-demand curing of polydimethylsiloxane (PDMS) using the photothermal effect of
gold nanoparticles.
AB - The photothermal effect of gold nanoparticles (AuNPs) produces extremely
localized heat that can be harnessed to drive large scale chemical reactions by
simultaneously generating many individual reactions on the nanoscale. We use the
photothermal effect to enhance the curing rate of polydimethylsiloxane (PDMS) by
a factor of 4.9 * 109. Photothermal curing occurs via crosslinking reactions
between vinyl and Si-H groups of the pre-polymer, and the course of the reaction
was followed by monitoring the disappearance of infrared bands associated with
these functional groups. Using mass spectroscopy, we verify that the major
polymer m/z peaks are identical for both traditionally and photothermally cured
polymers, indicating that the photothermal effect of AuNPs is an effective way in
which to supply on-demand curing of PDMS.
PMID- 28513706
TI - Control over the magnetism and transition between high- and low-spin states of an
adatom on trilayer graphene.
AB - Using density-functional theory, we investigate the electronic and magnetic
properties of an adatom (Na, Cu and Fe) on ABA- and ABC-stacked (Bernal and
rhombohedral) trilayer graphenes. In particular, we study the influence of an
applied gate voltage on magnetism, as it modifies the electronic states of the
trilayer graphene (TLG) as well as changes the adatom spin states. Our study
performed for a choice of three different adatoms (Na, Cu, and Fe) shows that the
nature of adatom-graphene bonding evolves from ionic to covalent in moving from
an alkali metal (Na) to a transition metal (Cu or Fe). Applying an external
electric field (EEF) to TLG systems with different stacking orders results in the
transition between high- and low-spin states in the latter case (Cu, Fe) and
induces a little of magnetism in the former (Na) without magnetism in the absence
of an external electric field. Our study would be useful for controlled adatom
magnetism and (organic) spintronic applications in nanotechnology.
PMID- 28513707
TI - Systematic study of interdependent relationship on gold nanorod synthesis
assisted by electron microscopy image analysis.
AB - Here, we systematically investigated the independent, multiple, and synergic
effects of three major components, namely, ascorbic acid (AA), seed, and silver
ions (Ag+), on the characteristics of gold nanorods (GNRs), i.e., longitudinal
localized surface plasmon resonance (LSPR) peak position, shape, size, and
monodispersity. To quantitatively assess the shape and dimensions of GNRs, we
used an automated transmission electron microscopy image analysis method using a
MATLAB-based code developed in-house and the concept of solidity, which is the
ratio between the area of a GNR and the area of its convex hull. The solidity of
a straight GNR is close to 1, while it decreases for both dumbbell- and dogbone
shaped GNRs. We found that the LSPR peak position, shape, and monodispersity of
the GNRs all altered simultaneously with changes in the amounts of individual
components. For example, as the amount of AA increased, both the LSPR peak and
solidity decreased, while the polydispersity increased. In contrast, as the
amount of seeds increased, both the LSPR and solidity increased, while the
monodispersity improved. More importantly, we found that the influence of each
component can actually change depending on the composition of the GNR growth
solution. For instance, the LSPR peak position red-shifted as the amount of AA
increased when the seed content was low, whereas it blue-shifted when the seed
content was high.
PMID- 28513708
TI - Symmetry-breaking charge transfer in the excited state of directly linked push
pull porphyrin arrays.
AB - Herein, we revealed a symmetry-breaking charge transfer (SBCT) process in the
excited state of a directly linked push-pull porphyrin dyad (AD) and triad (ADA)
via spectroscopic measurements including steady-state absorption and
fluorescence, time-resolved fluorescence (TRF), femtosecond transient absorption
(fs-TA), and time-resolved infrared (TRIR) measurements. Unprecedented broad
fluorescence spectra were observed for porphyrin arrays in polar solvents; these
were attributed to the existence of a charge transfer state as evidenced by the
TRF measurements. TA measurements also revealed emerging features of a CT state
for AD and ADA in polar solvents. These dynamics were also confirmed via TRIR
measurements, which provided further information on the solvation and structural
relaxation processes of the SBCT process. This is the first observation of an
SBCT process in porphyrin arrays, providing fundamental understanding of the
strongly coupled porphyrin arrays. Thus, the results of this study reveal the
potential of the porphyrin arrays in relevant applications requiring SBCT.
PMID- 28513709
TI - Correction: Optofluidic time-stretch imaging - an emerging tool for high
throughput imaging flow cytometry.
AB - Correction for 'Optofluidic time-stretch imaging - an emerging tool for high
throughput imaging flow cytometry' by Andy K. S. Lau et al., Lab Chip, 2016, 16,
1743-1756.
PMID- 28513710
TI - Are highly morphed peptide frameworks lurking silently in microbial genomes
valuable as next generation antibiotic scaffolds?
AB - Antibiotics are a therapeutic class that, once deployed, select for resistant
bacterial pathogens and so shorten their useful life cycles. As a consequence new
versions of antibiotics are constantly needed. Among the antibiotic natural
products, morphed peptide scaffolds, converting conformationally mobile, short
lived linear peptides into compact, rigidified small molecule frameworks, act on
a wide range of bacterial targets. Advances in bacterial genome mining,
biosynthetic gene cluster prediction and expression, and mass spectroscopic
structure analysis suggests many more peptides, modified both in side chains and
peptide backbones, await discovery. Such molecules may turn up new bacterial
targets and be starting points for combinatorial or semisynthetic manipulations
to optimize activity and pharmacology parameters.
PMID- 28513711
TI - A novel approach for fabricating highly tunable and fluffy bioinspired 3D
poly(vinyl alcohol) (PVA) fiber scaffolds.
AB - The excellent biocompatibility, biodegradability and chemo-thermal stability of
poly(vinyl alcohol) (PVA) have been harnessed in diverse practical applications.
These properties have motivated the fabrication of high performance PVA based
nanofibers with adequate control over the micro and nano-architectures and
surface chemical interactions. However, the high water solubility and
hydrophilicity of the PVA polymer limits the application of the electrospun PVA
nanofibers in aqueous environments owing to instantaneous dissolution. In this
work, we report a novel yet facile concept for fabricating extremely light,
fluffy, insoluble and stable three dimensional (3D) PVA fibrous scaffolds
with/without coating for multifunctional purposes. While the solubility,
morphology, fiber density and mechanical properties of nanofibers could be tuned
by optimizing the cross-linking conditions, the surface chemical reactivity could
be readily enhanced by coating with a polydopamine (pDA) bioinspired polymer
without compromising the stability and innate properties of the native PVA fiber.
The 3D pDA-PVA scaffolds exhibited super dye adsorption and constructive
synergistic cell-material interactions by promoting healthy adhesion and
viability of the human mesenchymal stem cells (hMSCs) within 3D micro-niches. We
foresee the application of tunable PVA 3D as a highly adsorbent material and a
scaffold material for tissue regeneration and drug delivery with close
consideration of realistic in vivo parameters.
PMID- 28513712
TI - Charge transport in C60-based single-molecule junctions with graphene electrodes.
AB - We investigate charge transport in C60-based single-molecule junctions with
graphene electrodes employing a combination of density functional theory (DFT)
electronic structure calculations and Landauer transport theory. In particular,
the dependence of the transport properties on the conformation of the molecular
bridge and the type of termination of the graphene electrodes is investigated.
Furthermore, electron pathways through the junctions are analyzed using the
theory of local currents. The results reveal, in agreement with previous
experiments, a pronounced dependence of the transport properties on the bias
polarity, which is rationalized in terms of the electronic structure of the
molecule. It is also shown that the edge states of zigzag-terminated graphene
induce additional transport channels, which dominate transport at low voltages.
The importance of the edge states for transport depends profoundly on the
interface geometry of the junctions.
PMID- 28513713
TI - One-step hydrothermal synthesis of photoluminescent carbon nanodots with
selective antibacterial activity against Porphyromonas gingivalis.
AB - Carbon dots (CDs) with high quantum yield (QY), low toxicity and good
biocompatibility are the major quests of biomedical research. In this paper, we
develop a green, simple hydrothermal approach to synthesize water-soluble,
nontoxic, highly photoluminescent carbon nanodots (CNDs) from Metronidazole,
which possess selective antibacterial activity against obligate anaerobes for the
first time. Metronidazole was used as a sole precursor to prepare CNDs at 250
degrees C (CNDs-250) for 8 h. After the CNDs-250 with an average size of 2.9 nm,
consisting of a highly carbon crystalline core and various surface groups were
obtained, the formation and fluorescence mechanisms of CNDs were further explored
by adjusting the reaction time and reaction temperatures, respectively.
Biological experimental data proved that CNDs-250 can only inhibit the growth of
obligate anaerobes, such as Porphyromonas gingivalis (P. gingivalis) directly,
instead of further functionalization. Besides, CNDs-250 with a QY around 28.1%
exhibit an obvious excitation-dependent emission, which will be conducive to
multicolor bioimaging. And it may not only develop a new approach for researchers
to prepare multifunctional CDs, but also provide a valuable strategy for the
theranostics of some diseases as well as other fields.
PMID- 28513714
TI - Highly water-stable rare ternary Ag-Au-Se nanocomposites as long blood
circulation time X-ray computed tomography contrast agents.
AB - X-ray computed tomography (CT) is a powerful and widely used medical non-invasive
technique that often requires intravenous administration of contrast agents (CAs)
to better visualize soft tissues. In this work, we have developed a novel CT
contrast agent based on ternary Ag-Au-Se chalcogenide nanoparticles (NP). A
facile ligand exchange by using a 3 kDa PEGylated ligand with a dithiol
dihydrolipoic acid as an anchor group resulted in highly water-soluble and
monodisperse nanoparticles. These PEGylated ternary NPs were tested in vivo in
mice, showing slow uptake by the mononuclear phagocyte system, long blood
circulation times, low toxicity, and very good X-ray contrast, thus being
promising candidates as CT contrast agents for clinical applications.
PMID- 28513715
TI - Heterogeneous Cu-Pd binary interface boosts stability and mass activity of atomic
Pt clusters in the oxygen reduction reaction.
AB - A ternary metallic CuPdPt nanocatalyst (NC) is synthesized using a wet chemical
reduction method, which is sequentially designed, in the presence of acid treated
carbon nanotubes. This NC is a nanocrystal with a configuration of a Cu@Pd core
and atomic Pt clusters (~9 wt%) on the top (Cu@Pd/Pt). A residual current of
92.6%, 5.2 times higher than that of commercial Pt catalysts (at 0.85 V vs. RHE),
is retained after 40 000 cycles of an accelerated degradation test (ADT). Atomic
and electronic structure analyses show that such exclusive stability mainly
results from electron localization at Pt clusters in heterogeneous interfaces of
the Cu-Pd core. Most importantly, we develop a robust ternary NC, which shows
outstanding MA, superior chemical durability, and ~90 wt% lower Pt loading than
commercial Pt NCs in the oxygen reduction reaction.
PMID- 28513716
TI - Combining light-harvesting with detachability in high-efficiency thin-film
silicon solar cells.
AB - Efforts to realize thin-film solar cells on unconventional substrates face
several obstacles in achieving good energy-conversion efficiency and integrating
light-management into the solar cell design. In this report a technique to
circumvent these obstacles is presented: transferability and an efficient light
harvesting scheme are combined for thin-film silicon solar cells by the
incorporation of a NaCl layer. Amorphous silicon solar cells in p-i-n
configuration are fabricated on reusable glass substrates coated with an
interlayer of NaCl. Subsequently, the solar cells are detached from the substrate
by dissolution of the sacrificial NaCl layer in water and then transferred onto a
plastic sheet, with a resultant post-transfer efficiency of 9%. The light
trapping effect of the surface nanotextures originating from the NaCl layer on
the overlying solar cell is studied theoretically and experimentally. The
enhanced light absorption in the solar cells on NaCl-coated substrates leads to
significant improvement in the photocurrent and energy-conversion efficiency in
solar cells with both 350 and 100 nm thick absorber layers, compared to flat
substrate solar cells. Efficient transferable thin-film solar cells hold a vast
potential for widespread deployment of off-grid photovoltaics and cost reduction.
PMID- 28513717
TI - In situ generation of less accessible Boc-imines from aldehydes: construction of
a quaternary carbon by the Mannich reaction or unprecedented aldol reaction.
AB - In situ generation of less accessible N-Boc-protected imines from aldehydes and
their application to the direct three-component Mannich reaction with beta
dicarbonyls were realized. The catalyst-free aldol reaction of ynals with beta
dicarbonyls was also developed.
PMID- 28513720
TI - Refinement of labile hydrogen positions based on DFT calculations of 1H NMR
chemical shifts: comparison with X-ray and neutron diffraction methods.
AB - Numerous gas phase electron diffraction, ultra-fast electron diffraction, X-ray
and neutron diffraction experiments on beta-dicarbonyl compounds exhibiting enol
enol tautomeric equilibrium, with emphasis on acetylacetone and dibenzoylmethane,
have so far been reported with conflicting results on the structural details of
the O-HO intramolecular hydrogen bond and resulted in alternative hypotheses on
the intramolecular hydrogen bond potential function either a double minimum
potential corresponding to two tautomeric forms in equilibrium or a single
symmetrical one. We demonstrate herein, firstly, that the DFT calculated OH 1H
NMR chemical shifts of acetylacetone and dibenzoylmethane exhibit a strong linear
dependence on the computed OO hydrogen bond length of ~-50 ppm A-1 and as a
function of the O-HO bond angle of ~1 ppm per degree, upon the transfer of the
hydrogen atom from the ground state toward the transition state. Secondly, the
refinement of labile hydrogen atomic positions in intramolecular hydrogen bonds
based on the root-mean-square deviation between experimentally determined and DFT
calculated 1H NMR chemical shifts in solution can provide high resolution
structures of O-H and O(H)O bond lengths and O-HO bond angles with an accuracy of
~10-2 A and ~0.5 degrees , respectively. Thirdly, the calculated 1H NMR chemical
shifts in solution of the two ground state tautomers in equilibrium of
acetylacetone and dibenzoylmethane are in excellent agreement with the
experimental value, even for moderate basis sets for energy minimization. In
contrast, the single symmetrical structure in a strongly delocalized system is a
transition state with calculated 1H NMR chemical shifts which strongly deviate
from the experimental value. Fourth, the DFT calculated ground state O-H bond
lengths of acetylacetone and dibenzoylmethane are in quantitative agreement with
the literature data which take into account the effect of quantum nuclear motion.
The DFT structural results are critically discussed with respect to the state-of
the-art variable temperature X-ray and neutron diffraction methods.
PMID- 28513721
TI - Programmable micrometer-sized motor array based on live cells.
AB - Trapping and transporting microorganisms with intrinsic motility are important
tasks for biological, physical, and biomedical applications. However, fast
swimming speed makes the manipulation of these organisms an inherently
challenging task. In this study, we demonstrated that an optoelectrical
technique, namely, optically induced dielectrophoresis (ODEP), could effectively
trap and manipulate Chlamydomonas reinhardtii (C. reinhardtii) cells swimming at
velocities faster than 100 MUm s-1. Furthermore, live C. reinhardtii cells
trapped by ODEP can form a micrometer-sized motor array. The rotating frequency
of the cells ranges from 50 to 120 rpm, which can be reversibly adjusted with a
fast response speed by varying the optical intensity. Functional flagella have
been demonstrated to play a decisive role in the rotation. The programmable cell
array with a rotating motion can be used as a bio-micropump to drive the liquid
flow in microfludic chips and may shed new light on bio-actuation.
PMID- 28513723
TI - Amphiphilic coatings for the protection of upconverting nanoparticles against
dissolution in aqueous media.
AB - Upconverting nanoparticles (UCNPs) of beta-NaYF4, co-doped with Yb3+ and Tm3+ and
21-36 nm large, were synthesized using a modified thermal decomposition method.
The as-synthesized UCNPs were coated with oleic acid and dispersed in nonpolar
media. Their morphology, size and crystal structure were analysed with
transmission electron microscopy and X-ray diffraction. The UCNPs showed a
fluorescence emission spectrum characteristic of Tm3+. Their dissolution in water
(pH ~ 4-5) and phosphate buffered saline (PBS, pH = 7.4) was determined from the
fraction of dissolved fluoride ions using a fluoride-ion-selective electrode. The
dissolution of bare UCNPs was much more prominent in PBS than in water. Two
amphiphilic coatings, poly(maleic anhydride-alt-1-octadecene)
bis(hexamethylene)triamine (PMAO-BHMT) and d-alpha-tocopheryl polyethylene glycol
succinate (TPGS) were tested for their effects on the dissolution of the UCNPs.
The coatings were formed directly on the as-synthesized UCNPs as was confirmed
with electrokinetic measurements, infrared spectroscopy and thermogravimetric
analyses. Both coatings enabled the dispersion of UCNPs in water, and improved
the fluorescence emission intensity with respect to the bare UCNPs. However, only
the PMAO-BHMT coating provided an effective protection against the dissolution of
the UCNPs and long-term colloidal stability in PBS, and did not show cytotoxicity
in EAhy926 endothelial cells.
PMID- 28513725
TI - Push-pull type meso-ester substituted BODIPY near-infrared dyes as contrast
agents for photoacoustic imaging.
AB - A series of push-pull type meso-ester substituted BODIPY dyes 1-4 with intense
near-infrared absorption, largely enhanced photoacoustic (PA) activity and
excellent photo-stability were synthesized. The impact of the electronic
structure on the PA activity was also discussed. Moreover, the in vitro and in
vivo PA imaging were investigated, which suggested a passive targeting capacity
in the tumor site.
PMID- 28513724
TI - Role of electronic correlations in photoionization of NO2 in the vicinity of the
2A1/2B2 conical intersection.
AB - We present the first ab initio multi-channel photoionization calculations for NO2
in the vicinity of the 2A1/2B2 conical intersection, for a range of nuclear
geometries, using our newly developed set of tools based on the ab initio
multichannel R-matrix method. Electronic correlation is included in both the
neutral and the scattering states of the molecule via configuration interaction.
Configuration mixing is especially important around conical intersections and
avoided crossings, both pertinent for NO2, and manifests itself via significant
variations in photoelectron angular distributions. The method allows for a
balanced and accurate description of the photoionization/photorecombination for a
number of different ionic channels in a wide range of photoelectron energies up
to 100 eV. Proper account of electron correlations is crucial for interpreting
time-resolved signals in photoelectron spectroscopy and high harmonic generation
(HHG) from polyatomic molecules.
PMID- 28513726
TI - Delocalized and localized donating-accepting Mn-C interactions in half-sandwich
cyclopentadienyl and pentadienyl complexes.
AB - The widely used cyclopentadienyl (Cp) ligand and the pentadienyl (Pdl) ligand
have very similar molecular orbitals (MOs) but they have significantly different
chemical behavior. The extensively mixing of the MOs in the Pdl ligand has
prevented a quantitative explanation of the observed differences between these
two ligands. In a series of synthesized close/open half sandwich manganese
phosphine carbonyls, the quantum theory of atoms in molecules and the interacting
quantum atom model allow us to quantify the accepting-donating capacities of both
ligands and to break down the M-dienyl bond into individual atomic interactions.
The Mn-Pdl bond is stronger, more localized and has a larger backbonding
contribution than the Mn-Cp bond. All carbon atoms in the Cp ring interact
similarly with the Mn center, whereas the Pdl's terminal carbon atoms exhibit a
strong donor and a moderate acceptor character, and C2 and C4 have an acceptor
character and C3 a donor character. Contrarily to the constrained five-membered
Cp ring, the stronger Mn-Pdl interaction can barely compensate for the large
destabilizing distortion of the backbone of the nonaromatic Pdl ligand.
PMID- 28513727
TI - Self-assembled air-stable magnesium hydride embedded in 3-D activated carbon for
reversible hydrogen storage.
AB - The rational design of stable, inexpensive catalysts with excellent hydrogen
dynamics and sorption characteristics under realistic environments for reversible
hydrogen storage remains a great challenge. Here, we present a simple and
scalable strategy to fabricate a monodispersed, air-stable, magnesium hydride
embedded in three-dimensional activated carbon with periodic synchronization of
transition metals (MHCH). The high surface area, homogeneous distribution of MgH2
nanoparticles, excellent thermal stability, high energy density, steric
confinement by carbon, and robust architecture of the catalyst resulted in a
noticeable enhancement of the hydrogen storage performance. The resulting MHCH-5
exhibited outstanding hydrogen storage performance, better than that of most
reported Mg-based hydrides, with a high storage density of 6.63 wt% H2, a rapid
kinetics loading in <5 min at 180 degrees C, superior reversibility, and
excellent long-term cycling stability over ~435 h. The significant reduction of
the enthalpy and activation energy observed in the MHCH-5 demonstrated
enhancement of the kinetics of de-/hydrogenation compared to that of commercial
MgH2. The origin of the intrinsic hydrogen thermodynamics was elucidated via
solid state 1H NMR. This work presents a readily scaled-up strategy towards the
design of realistic catalysts with superior functionality and stability for
applications in reversible hydrogen storage, lithium ion batteries, and fuel
cells.
PMID- 28513728
TI - A droplet-chip/mass spectrometry approach to study organic synthesis at nanoliter
scale.
AB - A droplet-based microfluidic device with seamless hyphenation to electrospray
mass spectrometry was developed to rapidly investigate organic reactions in
segmented flow providing a versatile tool for drug development. A chip-MS
interface with an integrated counterelectrode allowed for a flexible positioning
of the chip-emitter in front of the MS orifice as well as an independent
adjustment of the electrospray potentials. This was necessary to avoid
contamination of the mass spectrometer as well as sample overloading due to the
high analyte concentrations. The device was exemplarily applied to study the
scope of an amino-catalyzed domino reaction with low picomole amount of catalyst
in individual nanoliter sized droplets.
PMID- 28513729
TI - Stable small bubble clusters in two-dimensional foams.
AB - Key features of the mechanical response of amorphous particulate materials, such
as foams, emulsions, and granular media, to applied stress are determined by the
frequency and size of particle rearrangements that occur as the system
transitions from one mechanically stable state to another. This work describes
coordinated experimental and computational studies of bubble rafts, which are
quasi-two dimensional systems of bubbles confined to the air-water interface. We
focus on small mechanically stable clusters of four, five, six, and seven bubbles
with two different sizes with diameter ratio sigmaL/sigmaS ? 1.4. Focusing on
small bubble clusters, which can be viewed as subsystems of a larger system,
allows us to investigate the full ensemble of clusters that form, measure the
respective frequencies with which the clusters occur, and determine the form of
the bubble-bubble interactions. We emphasize several important results. First,
for clusters with N > 5 bubbles, we find using discrete element simulations that
short-range attractive interactions between bubbles give rise to a larger
ensemble of distinct mechanically stable clusters compared to that generated by
long-range attractive interactions. The additional clusters in systems with short
range attractions possess larger gaps between pairs of neighboring bubbles on the
periphery of the clusters. The ensemble of bubble clusters observed in
experiments is similar to the ensemble of clusters with long-range attractive
interactions. We also compare the frequency with which each cluster occurs in
simulations and experiments. We find that the cluster frequencies are extremely
sensitive to the protocol used to generate them and only weakly correlated to the
energy of the clusters.
PMID- 28513730
TI - Accurate measurement of the chirality of WS2 nanotubes.
AB - We describe the structural parameters and atomic positions of a single-walled WS2
nanotube. The structure factor is calculated in detail using analytic expressions
for both single-walled and multi-walled WS2 nanotubes. A zoning scheme has been
developed to obtain the ratio m/n from the electron diffraction patterns. The
procedure for determination of the chiral indices of both single-walled and multi
walled WS2 nanotubes and the tilt angle is illustrated in detail for either
normal incidence or inclined incidence. As an example of application, the
determination of the chiral indices of a five-shell WS2 nanotube was carried out
and the tilt angle was obtained as 17.7 degrees . The method developed here is
useful and valid to determine the atomic structure of WS2 nanotubes.
PMID- 28513732
TI - Reduced {001}-TiO2-x photocatalysts: noble-metal-free CO2 photoreduction for
selective CH4 evolution.
AB - The preparation of reduced TiO2 photocatalysts with high Ti3+ concentration is a
great challenge due to their instability in air. Here we report a new approach
for the synthesis of reduced TiO2 with {001} facets exposed via a hydrothermal
process. By the introduction of fluoride atoms, {001} and {101} facets are
formed, which act as hole and electron collectors, respectively, for charge
separation. By adjusting the volume of HF added, a rutile-anatase transition is
observed for the first time. EPR spectra confirm the generation of Ti3+ species
in the bulk of TiO2, and Ti3+ signals are studied in the anatase and rutile
phases separately. The quantified EPR shows that reduced TiO2 samples present 14
000-fold more spins compared to the pristine TiO2, and the intensity can reach as
high as 24.6 * 1019 spins per g. The obtained samples also have a unique
disordered layer with a thickness of 1-2 nm on their surfaces, which contributes
to the stabilization of the formed Ti3+ species by preventing their oxidation in
air. In addition, the synthesized reduced TiO2 samples also exhibit wide-spectrum
solar light absorption, especially in the near-infrared region. Owing to their
enhanced solar light absorption, improved electron-hole separation and special
facet exposure, these samples exhibit enhanced photocatalytic CO2 reduction
performance and high CH4 selectivity under solar light irradiation, in the
absence of a noble metal Pt as a co-catalyst.
PMID- 28513731
TI - Ag@Au nanoprism-metal organic framework-based paper for extending the glucose
sensing range in human serum and urine.
AB - In this work, we present a Ag@Au nanoprism-metal-organic framework-paper based
glucose sensor for rapid, sensitive, single-use and quantitative glucose
determination in human serum. To achieve painless measurement of glucose with a
non-invasive detection methodology, this biosensor was further tested in human
urine. In this approach, a new hybrid-Ag@Au nanoprism loaded in close proximity
to micrometer sized coordination polymers as phosphorescent luminophores
significantly enhanced the emission intensity due to metal-enhanced
phosphorescence and worked as reaction sites to support more dissolved oxygen.
Reports of enhanced phosphorescence intensity are relatively rare, especially at
room temperature. The true enhancement factor of Ag@Au-phosphorescent metal
organic frameworks on paper was deduced to be 110-fold, making it a better
optical type glucose meter. The results demonstrate the validity of the intensity
enhancement effect of the excitation of the overlap of the emission band of a
luminophore with the surface plasmon resonance band of Ag@Au nanoprisms. Ag@Au
nanoprisms were used not only to improve the detection limit of glucose sensing
but also to extend the glucose sensing range by enhancing the oxygen oxidation
efficiency. The oxidation of glucose as glucose oxidase is accompanied by oxygen
consumption, which increases the intensity of the phosphorescence emission. The
turn-on type paper-based biosensor exhibits a rapid response (0.5 s), a low
detection limit (0.038 mM), and a wide linear range (30 mM to 0.05 mM), as well
as good anti-interference, long-term longevity and reproducibility. Finally, the
biosensor was successfully applied to the determination of glucose in human serum
and urine.
PMID- 28513733
TI - Polylactic acid nano- and microchamber arrays for encapsulation of small
hydrophilic molecules featuring drug release via high intensity focused
ultrasound.
AB - Long term encapsulation combined with spatiotemporal release for a precisely
defined quantity of small hydrophilic molecules on demand remains a challenge in
various fields ranging from medical drug delivery, controlled release of
catalysts to industrial anti-corrosion systems. Free-standing individually sealed
polylactic acid (PLA) nano- and microchamber arrays were produced by one-step dip
coating a PDMS stamp into PLA solution for 5 s followed by drying under ambient
conditions. The wall thickness of these hydrophobic nano-microchambers is tunable
from 150 nm to 7 MUm by varying the PLA solution concentration. Furthermore,
small hydrophilic molecules were successfully in situ precipitated within
individual microchambers in the course of solvent evaporation after sonicating
the PLA@PDMS stamp to remove air-bubbles and to load the active substance
containing solvent. The cargo capacity of single chambers was determined to be in
the range of several picograms, while it amounts to several micrograms per cm2.
Two different methods for sealing chambers were compared: microcontact printing
versus dip-coating whereby microcontact printing onto a flat PLA sheet allows for
entrapment of micro-air-bubbles enabling microchambers with both ultrasound
responsiveness and reduced permeability. Cargo release triggered by external high
intensity focused ultrasound (HIFU) stimuli is demonstrated by experiment and
compared with numerical simulations.
PMID- 28513734
TI - Strained alkynes derived from 2,2'-dihydroxy-1,1'-biaryls; synthesis and copper
free cycloaddition with azides.
AB - A series of strained alkynes were prepared from 2,2'-dihydroxy-biaryls. Several
were characterised by X-ray crystallography, revealing strained C(sp)-C(sp)
C(sp3) bond angles in the range of 163-167 degrees . Their cycloadditions with
azides proceed without a catalyst. Functionalised versions of these reagents have
potential applications to materials synthesis and bioconjugations.
PMID- 28513735
TI - Highly efficient genome editing of human hematopoietic stem cells via a nano
silicon-blade delivery approach.
AB - Recently, the clustered regularly interspaced short palindromic repeats (CRISPR)
Cas9 bacterial immunity system has opened a promising avenue to treat genetic
diseases that affect the human hematopoietic stem cells (HSCs). Therefore,
finding a highly efficient delivery method capable of modifying the genome in the
hard-to-transfect HSCs, combined with the advanced CRISPR-Cas9 system, may meet
the challenges for dissecting the hematologic disease mechanisms and facilitate
future clinical applications. Here, we developed an effective HSC-specified
delivery microfluidic chip to disrupt the cell membrane transiently by inducing
rapid mechanical deformation that allowed the delivery of biomaterials into the
cytoplasm from the surrounding matrix. Compared with the previous designs, the
new nano-silicon-blade structure was specifically optimized for HSCs. Using the
silicon substrate, the sharpness and rigidity of the nano-blade constriction was
largely enhanced to improve the biomaterials delivery efficiency. We achieved
highly efficient delivery results by transporting various macro-molecules into
the HSCs. Moreover, the treated HSCs possess high viability and maintain inherent
pluripotency after the delivery via the Nano-Blade Chip (NB-Chip). Subsequently,
we disrupted the p42 isoform in C/EBPalpha on the NB-Chip and induced HSCs into a
myeloid proliferation behavior. In conclusion, the NB-Chip provides a harmless,
rapid and high-throughput gene editing approach for the HSC study and
therapeutics.
PMID- 28513736
TI - Photosensitization of CuI - the role of visible light induced CuI-> CuII
transition in photocatalytic degradation of organic pollutants and inactivation
of microorganisms.
AB - Bare and photosensitized copper iodides were tested in photocatalysed degradation
of an organic dye (Acid Red 1) and inactivation of fungi (Saccharomyces
cerevisiae). CuI, with the band gap energy slightly lower than that of TiO2,
appeared to be highly efficient in these processes. Sensitization of copper
iodide was achieved by surface modification with [Cu(SCN)2(phen)2]. The
photosensitization mechanism encompasses a metal to metal charge transfer, CuI->
CuII. The applied photosensitizer binds to CuI through thiocyanate ligands
resulting in the formation of an active CuII/CuI hybrid photocatalyst
([CuII(SCN)2(phen)2]@CuII). Its absorption edge is red shifted towards a lower
energy when compared with bare CuI, resulting in enhanced visible light induced
photocatalytic activity. The studied materials appeared to be photoactive in
current generation, degradation of organic compounds and inactivation of fungi.
PMID- 28513738
TI - Role of Ni in hetero-architectured NiO/Ni composites for enhanced catalytic
performance.
AB - A facile, one-step combustion synthesis in solution is reported for preparing
hetero-architectured NiO/Ni nanocomposites using different organic fuels. The
prepared nanocomposites were physicochemically characterized for crystal
structure, functional groups, and morphology. It was found that the content of Ni
in the nanocomposite varied due to different combustion fuels. A photocatalytic
(PC) investigation of these nanocomposites was performed using rhodamine 6G (RG)
under UV light. A citric acid combusted NiO/Ni (N-CA) composite containing 20% Ni
phase showed the highest photoactivity in comparison to pure NiO due to its large
porous channels and high surface area (~28 +/- 2 m2 g-1). The N-CA catalyst was
further evaluated for the degradation of cationic, anionic dyes and chloro/nitro
phenols under both UV and visible light. Photoelectrocatalysis (PEC) of RG with N
CA resulted in complete degradation of the dye. The mechanism governing the
catalytic processes was determined from the trapping experiments. The potential
reasons for the enhanced photoactivity of the NiO/Ni nanocomposite were that Ni
acted as an electron sink, and the applied bias of +1.0 V separated the electron
hole, reducing its rate of recombination.
PMID- 28513737
TI - Dimeric and trimeric derivatives of the azinomycin B chromophore show enhanced
DNA binding.
AB - To explore the utility of the azinomycin B chromophore as a platform for the
development of major-groove binding small molecules, we have prepared a series of
3-methoxy-5-methylnaphthalene derivatives containing diamine, triamine, and
carbohydrate linker moieties. All bis- and tris-azinomycin derivatives are
intercalators that display submicromolar binding affinities for calf-thymus DNA,
as revealed by viscometry measurements and fluorescent intercalator displacement
(FID) assays, respectively. Although the tightest binding ligand 1d (Ka = 2.42 *
107 M-1) has similar affinities for sequence diverse polynucleotides, competition
binding studies with methylated phage DNA and known major and minor groove
binding small molecules suggest that the tether moiety linking the naphthalene
chromophores may occupy the major groove of DNA.
PMID- 28513739
TI - Vapour-liquid interfacial properties of square-well chains from density
functional theory and Monte Carlo simulation.
AB - The statistical associating fluid theory for attractive potentials of variable
range (SAFT-VR) density functional theory (DFT) developed by [Gloor et al., J.
Chem. Phys., 2004, 121, 12740-12759] is used to predict the interfacial behaviour
of molecules modelled as fully-flexible square-well chains formed from
tangentially-bonded monomers of diameter sigma and potential range lambda =
1.5sigma. Four different model systems, comprising 4, 8, 12, and 16 monomers per
molecule, are considered. In addition to that, we also compute a number of
interfacial properties of molecular chains from direct simulation of the vapour
liquid interface. The simulations are performed in the canonical ensemble, and
the vapour-liquid interfacial tension is evaluated using the wandering interface
(WIM) method, a technique based on the thermodynamic definition of surface
tension. Apart from surface tension, we also obtain density profiles, coexistence
densities, vapour pressures, and critical temperature and density, paying
particular attention to the effect of the chain length on these properties.
According to our results, the main effect of increasing the chain length (at
fixed temperature) is to sharpen the vapour-liquid interface and to increase the
width of the biphasic coexistence region. As a result, the interfacial thickness
decreases and the surface tension increases as the molecular chains get longer.
The interfacial thickness and surface tension appear to exhibit an asymptotic
limiting behaviour for long chains. A similar behaviour is also observed for the
coexistence densities and critical properties. Agreement between theory and
simulation results indicates that SAFT-VR DFT is only able to predict
qualitatively the interfacial properties of the model. Our results are also
compared with simulation data taken from the literature, including the vapour
liquid coexistence densities, vapour pressures, and surface tension.
PMID- 28513740
TI - l-Ornithine stimulates growth hormone release in a manner dependent on the
ghrelin system.
AB - We found that intraduodenal administration of l-ornithine (l-Orn) stimulates
growth hormone (GH) secretion in Wistar rats, and then investigated its
mechanism. GH-releasing activity after intraduodenal administration of l-Orn was
blocked by [d-Lys3]-GHRP-6, an antagonist of the ghrelin receptor; however, l-Orn
(100 MUM) has no affinity for the ghrelin receptor, suggesting that the GH
releasing activity of l-Orn is mediated via ghrelin release and activation of the
ghrelin receptor. Intraduodenally administered l-Orn increased ghrelin mRNA
expression in the duodenum but not in the stomach or hypothalamus. In addition, l
Orn-induced GH-releasing activity was inhibited by propranolol, an antagonist of
beta-adrenergic receptor, which is known to be coupled to ghrelin release. In
conclusion, intraduodenally administered l-Orn stimulates GH secretion through
the sympathetic nervous and ghrelin systems.
PMID- 28513741
TI - Magneto-structural correlations in a family of di-alkoxo bridged chromium dimers.
AB - A series of di-alkoxo bridged Cr(iii) dimers have been synthesised using pyridine
alcohol ligands. The structures fall into four general categories and are of
formula: [Cr2(OMe)2(pic)4].1/2MeOH.1/2Et2O (1), [Cr2(hmp)2(pic)2X2] (where X = Cl
(2), Br (3)), [Cr2(L)2Cl4(A)2].2S (where L = hmp, A = H2O and S = Et2O (4); L =
hmp, A = pyridine and S = pyridine (5); L = hmp, A = 4-picoline and no S (6); L =
hep, A = H2O and S = MeCN (7)), and [Cr(hmp)(hmpH)Cl2].MeCN (8). Direct current
(DC) magnetic susceptibility measurements show relatively weak antiferromagnetic
exchange interactions between the Cr(iii) centres with J values <|15| cm-1 in all
of the complexes measured. DFT calculations performed on complexes 1-8 reproduce
both the sign and strength of the exchange interactions found experimentally, and
confirm that the magnitude and sign of the J value is strongly dependent upon the
orientation of the dihedral angle formed between the bridging Cr2O2 plane and the
O-R vector of the bridging group (theta), and the Cr-O-Cr-O dihedral angle (psi).
PMID- 28513742
TI - Structural stability and intriguing electronic properties of two-dimensional
transition metal dichalcogenide alloys.
AB - Based on the first-principles calculations, we systematically studied the
structures and electronic properties of two-dimensional (2D) transition metal
dichalcogenide (TMD) alloys with half-to-half mixing of S and Se. Using the
chemical potentials of S and Se, the energetic phase diagrams for both single
phases and mixed phases of TMD were constructed. A new heterolayer structure (for
Sc and Ti) and alternating structure (for Cr, Mn, Fe, Zr, Mo, and W) were
proposed for the first time, which were thermodynamically stable for MSSe alloys
under the S-poor (relatively low chemical potential of S) and Se-rich (relatively
high chemical potential of Se) conditions, and further compared with the
disordered structures. Moreover, band gaps, carrier effective mass, and work
functions were calculated for these stable mixed phases. Compared to the single
phases of MS2 and MSe2, MSSe alloys showed superior electronic properties
including tunable band gaps and work functions. Importantly, the significantly
reduced effective mass of the carriers in the MSSe alloys may induce higher
carrier mobility, providing better performance of TMD materials in electronic
devices.
PMID- 28513743
TI - Adsorption differences between low coverage enantiomers of alanine on the chiral
Cu{421}R surface.
AB - Chiral separation using heterogeneous methods has long been sought after. Chiral
metal surfaces have the potential to make it possible to model these systems
using small amino acids, the building blocks for proteins. A comparison of
submonolayer concentrations of alanine enantiomers adsorbed onto Cu{421}R has
revealed a large geometrical differences between the two molecules as compared to
the saturated coverage. Large differences were observed in HR-XPS and NEXAFS and
complemented by theoretical DFT calculations. At approximately one third of a
monolayer a comparison of the C1s XPS signal showed a shift in the methyl group
of more than 300 meV indicating that the two enantiomers are in different
chemical environments. NEXAFS spectroscopy confirmed the XPS variations and
showed large differences in the orientation of the adsorbed molecules. Our DFT
results show that the l-enantiomer is energetically the most stable in the {311}
microfacet configuration. In contrast to the full monolayer coverage, these lower
coverages showed enhanced selectivity.
PMID- 28513744
TI - High-affinity recognition of the human C-reactive protein independent of
phosphocholine.
AB - A high-affinity polypeptide conjugate 4-C25L22-DQ, has been developed for the
molecular recognition of the human C-reactive protein, CRP, a well-known
inflammation biomarker. CRP is one of the most frequently quantified targets in
diagnostic applications and a target in drug development. With the exception of
antibodies, most molecular constructs take advantage of the known affinity for
CRP of phosphocholine that depends on Ca2+ for its ability to bind. 4-C25L22-DQ
which is unrelated to phosphocholine binds in the absence of Ca2+ with a
dissociation constant of 760 nM, an order of magnitude lower than that of
phosphocholine, the KD of which is 5 MUM. The small organic molecule 2-oxo-1,2
dihydroquinoline-8-carboxylic acid (DQ) was designed based on the structural
similarities between three hits from a set of compounds selected from a building
block collection and evaluated with regards to affinity for CRP by NMR
spectroscopy. 4-C25L22-DQ was shown in a competition experiment to bind CRP three
orders of magnitude more strongly than DQ itself, and in a pull-down experiment 4
C25L22-DQ was shown to extract CRP from human serum. The development of a robust
and phosphocholine-independent recognition element provides unprecedented
opportunities in bioanalytical applications in vivo and in vitro under conditions
where the concentration of Ca2+ ions is low, or where Ca2+ binding agents such as
EDTA or heparin are needed to prevent blood coagulation. The identification from
a compound library of a small organic molecule and its conjugation to a small set
of polypeptides, none of which were previously known to bind CRP, illustrates a
convenient and general route to selective high-affinity binders for proteins with
dissociation constants in the MUM to nM range for which no small molecule ligands
are known.
PMID- 28513745
TI - In vivo fermentation of a Pleurotus eryngii polysaccharide and its effects on
fecal microbiota composition and immune response.
AB - A novel, homogeneous Pleurotus eryngii polysaccharide (PEP) (molecular weight 426
kDa, purity 91.25 +/- 3.14%) which mainly consisted of glucose with beta-type
glycosidic linkages was used to investigate in vivo fermentation behavior and
effects on immune response in mice. Different doses (0.2, 0.4, 0.8 g per kg body
weight) were orally administered to the mice for a period of six weeks. The
results showed that the SCFA concentration, pH value, and moisture contents of
cecum and colon contents were significantly altered with high-dose PEP treatment
compared to the control group (P < 0.05). Moreover, the fecal microbiota in the
PEP treated group was found to be structurally different compared to the control
group; especially, the Porphyromonadaceae, Rikenellaceae, Bacteroidaceae and
Lactobacillaceae abundances were all increased at the family level. In addition,
the exerted immune response was significantly altered after the high-dose PEP
oral administration. This exploratory study indicated that intake of PEP could
have a positive role in gastrointestinal tract health.
PMID- 28513746
TI - Structure-functionality relationship and pharmacological profiles of Pseudomonas
aeruginosa alkylquinolone quorum sensing modulators.
AB - An important paradigm in anti-infective research is the antivirulence concept.
Pathoblockers are compounds which disarm bacteria of their arsenal of virulence
factors. PqsR is a transcriptional regulator controlling the production of such
factors in Pseudomonas aeruginosa, most prominently pyocyanin. In this work, a
series of tool compounds based on the structure of the natural ligand 2-heptyl-4
quinolone (HHQ) were used for probing the structure-functionality relationship.
Four different profiles are identified namely agonists, antagonists, inverse
agonists and biphasic modulators. Molecular docking studies revealed that each
class of the PqsR modulators showed distinctive interactions in the PqsR binding
domain. It was found that the substituents in position 3 of the quinolone core
act as a switch between the different profiles, according to their ability to
donate or accept a hydrogen bond, or form a hydrophobic interaction. Finally, it
was shown that only inverse agonists were able to strongly inhibit pyocyanin
production.
PMID- 28513747
TI - Structural and electronic elucidation of a N-heterocyclic silylene vanadocene
adduct.
AB - The solid and solution state structure of the vanadium(ii) N-heterocyclic
silylene (NHSi) complex, [(SiIPr)V(Cp)2] (1) is reported (SiIPr: 1,3-bis(2,6
diisopropylphenyl)-1,3-diaza-2-silacyclopent-4-en-2-ylidene). The electronic
structure of 1 is probed using a combination of magnetic measurements, EPR
spectroscopy and computational studies. The V-Si bond strength and complex
forming mechanism between vanadocene and an NHSi ligand is elucidated using
computational methods.
PMID- 28513748
TI - Development of stable Pickering emulsions/oil powders and Pickering HIPEs
stabilized by gliadin/chitosan complex particles.
AB - In this paper, we demonstrate the use of gliadin/chitosan complex particles
(GCCPs) as particulate stabilizers of oil-in-water emulsions of natural oils and
water. For this purpose, we fabricated GCCPs through a facile anti-solvent
procedure and demonstrated their usage in the formation of Pickering emulsions
and Pickering high internal phase emulsions (HIPEs). The GCCPs can be used to
produce surfactant-free o/w Pickering emulsions and Pickering HIPEs;
unfortunately these emulsions were labile to coalescence. NaCl addition and/or pH
regulation, and the combination were used to modify the surface wettability of
the complex particles to achieve stable emulsions. The microstructures, e.g.,
interfacial frameworks, GCCP partition between the continuous phase and
interfacial region, and the state of the droplets, of Pickering emulsions were
visualized by confocal laser scanning microscopy (CLSM), confirming that the
inclusion of NaCl and slightly adjusting pH toward 4.0 and/or 5.0 benefited the
adsorption and accumulation of colloid particles at the droplet surface to form
an engineered interfacial structure, bridging droplets together through a
percolating layer of colloidal particles at the oil/water interface. A schematic
representation for the formation route of the emulsions is proposed to relate the
physical performance and rheological property with the interfacial structures and
aggregate behaviors in the Pickering system stabilized by the complex particles.
Interestingly, direct freeze-drying of the emulsions transformed unstable
Pickering emulsions into stable oil powders. This study opens a promising route
based on Pickering HIPEs or oil powders to structure liquid oils into solid-like
fats without artificial trans-fat, which outlines new directions for future
fundamental research.
PMID- 28513749
TI - Selective trihydroxylated azepane inhibitors of NagZ, a glycosidase involved in
Pseudomonas aeruginosa resistance to beta-lactam antibiotics.
AB - The synthesis of a series of d-gluco-like configured 4,5,6-trihydroxyazepanes
bearing a triazole, a sulfonamide or a fluorinated acetamide moiety at C-3 is
described. These synthetic derivatives have been tested for their ability to
selectively inhibit the muropeptide recycling glucosaminidase NagZ and to thereby
increase sensitivity of Pseudomonas aeruginosa to beta-lactams, a pathway with
substantial therapeutic potential. While introduction of triazole and sulfamide
groups failed to lead to glucosaminidase inhibitors, the NHCOCF3 analog proved to
be a selective inhibitor of NagZ over other glucosaminidases including human O
GlcNAcase and lysosomal hexosaminidases HexA and B.
PMID- 28513750
TI - Enantioselective magnesium-catalyzed transformations.
AB - This review updates the major progress in the field of enantioselective
transformations promoted by chiral magnesium catalysts, covering the literature
since 2007, illustrating the power of these mild Lewis acid catalysts to provide
a wide variety of novel asymmetric reactions.
PMID- 28513751
TI - Iodine-mediated synthesis of sulfur-bridged enaminones and chromones via double
C(sp2)-H thiolation.
AB - The reactions of various enaminones with elemental sulfur giving rise to both
sulfur-bridged enaminones and chromones have been realized via iodine promotion.
All products were furnished by means of double C(sp2)-H bond thiolation without
using any metal catalyst or sensitive oxidant, providing a simple and efficient
protocol for the synthesis of diverse sulfur derivatives of enaminones.
PMID- 28513752
TI - Comparison of PM2.5 carbonaceous pollutants between an urban site in Shanghai and
a background site in a coastal East China Sea island in summer: concentration,
composition and sources.
AB - Nine paired samples of atmospheric particulate matter with an aerodynamic
diameter less than or equal to 2.5 MUm (PM2.5) were collected concurrently from
an urban site in Shanghai, China and a background site in Huaniao Island (HNI) in
the coastal East China Sea (ECS) between July 21 and 29, 2011. The samples were
analyzed for 16 United States Environmental Protection Agency (USEPA) priority
polycyclic aromatic hydrocarbons (PAHs), n-alkanes (20 species, C14-C33), hopanes
(10 species, C29-C32), and steranes (12 species, C27-C29). These two sites,
approximately 66 km apart, are both on the pathway of land-based pollutants as
they are transported to the ECS by seasonal winds. As expected, concentrations in
Shanghai were higher (average: 8.4 and 67.8 ng m-3 for the 16 PAHs and n-alkanes,
respectively) than those in HNI (average: 1.8 and 8.5 ng m-3, respectively). The
dominant contributor to the 16 PAHs in Shanghai was 5-6-ring PAHs (60.0%),
whereas 2-3-ring PAHs contributed the most (72.5%) in HNI. Plant waxes
contributed 45.7% and 25.9% of the n-alkanes in Shanghai and HNI, respectively,
implying a relatively greater contribution from petroleum residues to the n
alkanes in HNI. Principal component analysis (PCA) and the compositions of
hopanes and steranes highlighted a prominent contribution from traffic emissions
to carbonaceous PM2.5 aerosols. This study provides comprehensive details about
the sources, formation, and transport of pollutants from eastern China to the
coastal ECS.
PMID- 28513753
TI - Two-step conversion of carboxylic esters into distally fluorinated ketones via
ring cleavage of cyclopropanol intermediates: application of sulfinate salts as
fluoroalkylating reagents.
AB - Tertiary cyclopropanols easily available from carboxylic esters have been used in
the synthesis of distally fluorinated ketones. Cyclopropane ring cleavage
reactions in methanol with aqueous tert-butyl hydroperoxide in the presence of a
copper(ii) acetate catalyst and sodium triflinate (Langlois reagent) afford beta
trifluoromethyl ketones in 16-74% isolated yields. Sodium triflinate serves as a
precursor of reactive trifluoromethyl copper species, enabling ring-opening
trifluoromethylation, as evidenced by mechanistic studies. We also demonstrate
here that other sulfinate salts, such as sodium 1,1-difluoroethanesulfinate,
sodium 2-(4-bromophenyl)-1,1-difluoroethanesulfinate and sodium 1
(trifluoromethyl)cyclopropanesulfinate, can be used as fluoroalkylation reagents,
resulting in the corresponding fluorinated ketones.
PMID- 28513754
TI - Structural heterogeneity in a parent ground-state structure of AnPixJg2 revealed
by theory and spectroscopy.
AB - We investigated the red absorbing, dark stable state (Pr state) of the second GAF
domain of the cyanobacteriochrome AnPixJ (AnPixJg2) by a molecular dynamics
simulation of 1 MUs duration. Our results reveal two distinct conformational
isoforms of the chromophore, from which only one was known from crystallographic
experiments. The interconversion between both isoforms is accompanied by
alterations in the hydrogen bond pattern between the chromophore and the protein
and the solvation structure of the chromophore binding pocket. The existence of
sub-states in the Pr form of AnPixJg2 is supported by the results from
experimental 13C MAS NMR spectroscopy. Our finding is consistent with the
observation of structural heterogeneity in other cyanobacteriochromes and
phytochromes.
PMID- 28513756
TI - Divergent synthesis of biflavonoids yields novel inhibitors of the aggregation of
amyloid beta (1-42).
AB - Biflavonoids are associated with a variety of biologically useful properties.
However, synthetic biflavonoids are poorly explored within drug discovery. There
is considerable structural diversity possible within this compound class and
large regions of potentially biologically relevant biflavonoid chemical space
remain untapped or underexplored. Herein, we report the development of a modular
and divergent strategy towards biflavonoid derivatives which enabled the step
economical preparation of a structurally diverse collection of novel unnatural
biflavonoids. Preliminary studies established that the strategy could also be
successfully extended to the preparation of very rare triflavonoids, which are
also expected to be useful tools for biological intervention. Prompted by
previous inhibitory studies with flavonoid libraries, amyloid anti-aggregation
screening was performed, which led to the identification of several structurally
novel inhibitors of the aggregation of the amyloid beta peptide (Abeta42).
Aggregated Abeta42 is a pathological hallmark of Alzheimer's disease and the use
of small molecules to inhibit the aggregation process has been identified as a
potentially valuable therapeutic strategy for disease treatment. Methylated
biaurones were associated with highest levels of potency (the most active
compound had an IC50 value of 16 MUM), establishing this scaffold as a starting
point for inhibitor development.
PMID- 28513755
TI - Re-assembled casein micelles improve in vitro bioavailability of vitamin D in a
Caco-2 cell model.
AB - The pandemic of vitamin D (VD) deficiency, and the global rise in obesity
stimulate a need for staple low-fat foods and beverages enriched with VD. In
light of consumer demand for a clean label, the use of natural endogenous food
ingredients as delivery vehicles is of great interest. To this end, re-assembled
casein micelles (rCM) have been shown to help retain VD during processing and
shelf life and provide high bioavailability in low-fat milk and non-fat yoghurt.
This follow-up study focused on the performance of VD-loaded rCM after drying and
reconstitution, considering VD retention during simulated digestion, and the
subsequent in vitro bioavailability of the vitamin. rCM conferred great
protection to VD3 during simulated digestion with a significant increase in
vitamin retention for 1 h under gastric conditions. This observation is believed
to arise from the vitamin-casein binding and the system's natural gelation (curd
formation) near the casein isoelectric point that seclude the vitamin from
environmental stressors and couple its release with digestive proteolysis of the
rCM matrix. Vitamin absorption by Caco-2 cells from digested rCM was not
significantly different from the absorption of the digested free VD. However,
thanks to the highly protective effect of the rCM, against VD gastric
degradation, the overall effect of the rCM was a 4-fold higher bioavailability,
compared to the free VD.
PMID- 28513757
TI - [New drugs for horses and production animals in 2016].
AB - In 2016, only one newly developed active pharmaceutical ingredient for horses and
food-producing animals was released on the German market for veterinary drug
products. The immunomodulator Pegbovigrastim is now available as an injection
solution for cattle (Imrestor(r)). Four established veterinary active
pharmaceutical ingredients are available for further species: the ectoparasitic
Amitraz (Apitraz(r)) from the triazapentadiene group was additionally authorized
for honeybees, the expectorant Bromhexine (Exflow(r) Vet) for chickens, turkeys
and ducks and the macrolide antibiotic Gamithromycin (Zactran(r)) for pigs. The
dopamine D2 receptor agonist Cabergolin (Velactis(r)) was released for dairy
cattle. However, the authorization was suspended a few months after market
introduction because of severe side effects. Additionally, one veterinary drug
with a new combination of active ingredients as well as one active substance in
mono-preparation have been launched on the market for horses and food producing
animals.
PMID- 28513758
TI - [New drugs for small animals in 2016].
AB - In 2016, two active pharmaceutical ingredients were released on the German market
for small animals: the mineralocorticoid Desoxycorticosterone (Zycortal(r)) and
Sarolaner (Simparica(r)), an ectoparasiticide of the isoxazoline group. One
substance has been authorized for an additional species; Fluralaner
(Bravecto(r)), also an ectoparasiticide of the isoxazoline group, is now
authorized for use in cats. Additionally, one veterinary drug with a new
combination of active ingredients, one active substance in mono-preparation and
two veterinary drugs with a new pharmaceutical form have been launched on the
market for small animals.
PMID- 28513759
TI - [Diagnosis of leptospirosis in dogs].
AB - Rapid confirmation of the diagnosis leptospirosis is important in order to apply
appropriate treatment; in addition, infected dogs are a zoonotic risk. Culture
and isolation of living leptospires from blood, urine, or tissues is considered
the reference standard of diagnosis. However, sensitivity are low, and
leptospires require weeks to months to grow. Therefore, diagnosis of
leptospirosis is most commonly based on antibody testing or the detection of
Leptospira spp. DNA by PCR. Microscopic agglutination test (MAT) is currently
still the recommended confirmatory test for canine leptospirosis, despite its
numerous limitations (e. g., negative results in early infection, positive
results due to vaccine-associated antibodies). ELISA can differentiate between
IgG and IgM antibodies and thus, discriminate current infections from previous
vaccination or exposure. Point-of-care tests and in-house-PCR tests have recently
been developed for use in private practice allowing easy and immediate diagnosis.
However, only few data on sensitivity and specificity of these tests exist so
far. A reliable diagnosis can only be established in case of a positive PCR
result or a fourfold titre increase in MAT.
PMID- 28513760
TI - Cell therapy in the treatment of bipolar mania in an animal model: a proof of
concept study.
AB - INTRODUCTION: The rationale of mesenchymal stem cells (MSCs) as a novel
therapeutic approach in certain neurodegenerative diseases is based on their
ability to promote neurogenesis. Hippocampal atrophy has been related to bipolar
disorder (BD) in preclinical, imaging and postmortem studies. Therefore, the
development of new strategies to stimulate the neurogenesis process in BD is
crucial. OBJECTIVES: To investigate the behavioral and neurochemical changes
induced by transplantation of MSCs in a model of mania-like behavior induced by
lisdexamfetamine dimesylate (LDX). METHODS: Wistar rats (n=65) received one oral
daily dose of LDX (10 mg/kg) or saline for 14 days. On the 8th day of treatment,
the animals additionally received intrahippocampal saline or MSC (1 uL containing
25,000 cells) or lithium (47.5 mg/kg) as an internal experimental control. Two
hours after the last administration, behavioral and neurochemical analyses were
performed. RESULTS: LDX-treated rats had increased locomotor activity compared to
saline-saline rats (p=0.004), and lithium reversed LDX-related hyperactive
behavior (p<0.001). In contrast, the administration of MSCs did not change
hyperlocomotion, indicating no effects of this treatment on LDX-treated rats
(p=0.979). We did not find differences between groups in BDNF levels (p>0.05) in
the hippocampus of rats. CONCLUSION: Even though these results suggest that a
single intrahippocampal injection of MSCs was not helpful to treat hyperactivity
induced by LDX and neither influenced BDNF secretion, we cannot rule out the
possible therapeutic effects of MSCs. Further research is required to determine
direct effects of LDX on brain structures as well as in other pathophysiological
targets related to BD.
PMID- 28513762
TI - Water fluoridation in Brazilian cities at the first decade of the 21st century.
AB - OBJECTIVE: To assess the coverage of the fluoridation of the public water supply
in Brazilian municipalities at the first decade of the 21st century, according to
population size and municipal human development index (MHDI). METHODS: We have
used data produced by national information agencies and the United Nations
Development Programme. Population size was separated into < 10,000, 10,000
50,000, and > 50,000 inhabitants. The MHDI was classified into < 0.600, 0.600
0.699, 0.700-0.799, and > 0.799. Absolute and relative inequalities between
categories were evaluated using indicators of effect and total impact. RESULTS:
We have obtained information for 5,558 municipalities. The coverage rate of water
fluoridation increased from 67.7% to 76.3%. Approximately 884 (15.9%)
municipalities and 29,600,000 inhabitants started being benefited by the measure.
We have observed a significant expansion in municipalities with < 10,000
inhabitants (increase of 21.0 percentage points) and low or very low MHDI (17.7
percentage points). CONCLUSIONS: Population coverage of the public policy has
increased 8.6%, and we can also see significant reductions in absolute and
relative inequality according to population size and MHDI. Regarding municipal
coverage rate, there was also a reduction in inequality in all comparisons except
for absolute inequality between the categories of MHDI. The public policy has
operated as a factor of health protection in the context of the ongoing social
protection policies in the country. OBJETIVO: Avaliar a cobertura da fluoretacao
da agua de abastecimento publico em municipios brasileiros na primeira decada do
seculo XXI, segundo porte demografico e nivel de desenvolvimento humano municipal
(IDH-M). METODOS: Foram utilizados dados produzidos por agencias nacionais de
informacao e pelo Programa das Nacoes Unidas para o Desenvolvimento. O porte
demografico foi separado em < 10 mil; 10-50 mil; > 50 mil habitantes. O IDH-M foi
classificado em < 0,600; 0,600-0,699; 0,700-0,799; > 0,799. As desigualdades
absoluta e relativa entre as categorias foram avaliadas por meio de indicadores
de efeito e de impacto total. RESULTADOS: Foram obtidas informacoes para 5.558
municipios. A taxa de cobertura da fluoretacao da agua aumentou de 67,7% para
76,3%. Passaram a ser beneficiados pela medida 884 (15,9%) municipios, e 29,6
milhoes de habitantes. Observou-se ampliacao expressiva em municipios com < 10
mil habitantes (aumento de 21,0 pontos percentuais) e com IDH-M baixo ou muito
baixo (17,7 pontos percentuais). CONCLUSOES: A cobertura populacional da politica
publica aumentou 8,6%, sendo expressivas as reducoes das desigualdades absoluta e
relativa segundo o porte demografico e o IDH-M. Quanto a taxa de cobertura
municipal, houve tambem reducao da desigualdade em todas as comparacoes com
excecao da desigualdade absoluta entre as categorias de IDH-M. A politica publica
operou como fator de protecao sanitaria no contexto das politicas de protecao
social em curso no pais.
PMID- 28513761
TI - Socioeconomic determinants of access to health services among older adults: a
systematic review.
AB - OBJECTIVE: The objective of this study was to analyze the association between the
socioeconomic characteristics and the access to or use of health services among
older adults. METHODS: This is a systematic review of the literature. The search
has been carried out in the databases PubMed, LILACS and Web of Science, without
restriction of dates and languages; however we have included only articles
published in Portuguese, English, and Spanish. The inclusion criteria were:
observational design, socioeconomic factors as variables of interest in the
analysis of the access to or use of health services among older adults,
representative sample of the target population, adjustment for confounding
factors, and no selection bias. RESULTS: We have found 5,096 articles after
deleting duplicates and 36 of them have been selected for review after the
process of reading and evaluating the inclusion criteria. Higher income and
education have been associated with the use and access to medical appointments in
developing countries and some developed countries. The same association has been
observed in dental appointments in all countries. Most studies have shown no
association between socioeconomic characteristics and the use of inpatient and
emergency services. We have identified greater use of home visits in lower-income
individuals, with the exception of the United States. CONCLUSIONS: We have
observed an unequal access to or use of health services in most countries,
varying according to the type of service used. The expansion of the health care
coverage is necessary to reduce this unequal access generated by social
inequities.
PMID- 28513764
TI - Vulnerability to the transmission of human visceral leishmaniasis in a Brazilian
urban area.
AB - OBJECTIVE: To analyze the determinants for the occurrence of human visceral
leishmaniasis linked to the conditions of vulnerability. METHODS: This is an
ecological study, whose spatial analysis unit was the Territorial Analysis Unit
in Araguaina, State of Tocantins, Brazil, from 2007 to 2012. We have carried out
an analysis of the sociodemographic and urban infrastructure situation of the
municipality. Normalized primary indicators were calculated and used to construct
the indicators of vulnerability of the social structure, household structure, and
urban infrastructure. From them, we have composed a vulnerability index. Kernel
density estimation was used to evaluate the density of cases of human visceral
leishmaniasis, based on the coordinates of the cases. Bivariate global Moran's I
was used to verify the existence of spatial autocorrelation between the incidence
of human visceral leishmaniasis and the indicators and index of vulnerability.
Bivariate local Moran's I was used to identify spatial clusters. RESULTS: We have
observed a pattern of centrifugal spread of human visceral leishmaniasis in the
municipality, where outbreaks of the disease have progressively reached central
and peri-urban areas. There has been no correlation between higher incidences of
human visceral leishmaniasis and worse living conditions. Statistically
significant clusters have been observed between the incidences of human visceral
leishmaniasis in both periods analyzed (2007 to 2009 and 2010 to 2012) and the
indicators and index of vulnerability. CONCLUSIONS: The environment in
circumscribed areas helps as protection factor or increases the local
vulnerability to the occurrence of human visceral leishmaniasis. The use of
methodology that analyzes the conditions of life of the population and the
spatial distribution of human visceral leishmaniasis is essential to identify the
most vulnerable areas to the spread/maintenance of the disease. OBJETIVO:
Analisar determinantes para a ocorrencia da leishmaniose visceral humana
vinculados as condicoes de vulnerabilidade. METODOS: Estudo ecologico, cuja
unidade de analise espacial foi a Unidade de Analise Territorial em Araguaina,
TO, de 2007 a 2012. Foi realizada analise da situacao sociodemografica e de
infraestrutura urbana no municipio. Indicadores primarios normalizados foram
calculados e utilizados na construcao de indicadores de vulnerabilidade de
estrutura social, de estrutura domiciliar e de infraestrutura urbana. A partir
deles, foi composto um indice de vulnerabilidade. A estimativa de Kernel foi
utilizada para avaliar a densidade de casos de leishmaniose visceral humana, com
base nas coordenadas dos casos. O I-Moran Global Bivariado foi empregado para
verificar a existencia de autocorrelacao espacial entre a incidencia de
leishmaniose visceral humana e os indicadores e indice de vulnerabilidade. I
Moran Local Bivariado foi utilizado para identificar clusters espaciais.
RESULTADOS: Foi observado um padrao de disseminacao centrifuga da leishmaniose
visceral humana no municipio, em que surtos da doenca atingiram progressivamente
areas centrais e periurbanas. Houve correlacao entre maiores incidencias de
leishmaniose visceral humana e piores condicoes de vida. Foram observados
clusters estatisticamente significativos entre as incidencias de leishmaniose
visceral humana nos dois periodos analisados (2007 a 2009 e 2010 a 2012) e os
indicadores e indice de vulnerabilidade. CONCLUSOES: O ambiente em areas
circunscritas contribui como fator de protecao ou aumenta a vulnerabilidade local
a ocorrencia de leishmaniose visceral humana. O uso de metodologia que analisa as
condicoes de vida da populacao e distribuicao espacial da leishmaniose visceral
humana e essencial na identificacao de areas mais vulneraveis a
disseminacao/manutencao da doenca.
PMID- 28513763
TI - Interaction between demand-control and social support in the occurrence of common
mental disorders.
AB - OBJECTIVE: To analyze the interaction between the psychosocial aspects of work
and the occurrence of common mental disorders among health workers. METHODS: This
is a cross-sectional study conducted with a representative sample of workers of
the primary health care of five municipalities of the State of Bahia, Brazil, in
2012. The variable of outcome were the common mental disorders evaluated by the
SRQ-20, and the variables of exposure were high demand (high psychological demand
and low control over the work) and low social support in the workplace.
Interaction was checked by the deviation of the additivity of the effects for the
factors studied from the calculation of excess risk from interaction, proportion
of cases attributed to interaction, and the synergy index. RESULTS: The global
prevalence of common mental disorders was 21%. The group of combined exposure has
shown higher magnitude (high demand and low social support), reaching 28% when
compared to the 17% in the situation of no exposure (low demand and high social
support). CONCLUSIONS: The results strengthen the hypothesis of interaction
between the factors investigated, directing to the synergy of the effects.
OBJETIVO: Analisar a interacao entre aspectos psicossociais do trabalho e a
ocorrencia de transtornos mentais comuns entre trabalhadores da saude. METODOS:
Estudo transversal conduzido em amostra representativa de trabalhadores da
atencao basica de cinco municipios da Bahia em 2012. As variaveis desfecho foram
os transtornos mentais comuns avaliados pelo SRQ-20, as de exposicao foram a alta
exigencia (alta demanda psicologica e baixo controle sobre o proprio trabalho) e
o baixo apoio social no trabalho. A interacao foi verificada pelo afastamento da
aditividade dos efeitos para fatores estudados a partir do calculo do excesso de
risco devido a interacao, proporcao de casos atribuida a interacao e indice de
sinergia. RESULTADOS: A prevalencia global de transtornos mentais comuns foi de
21%. Apresentou maior magnitude no grupo de exposicao combinada (alta exigencia e
baixo apoio social), chegando a 28% quando comparada a 17% na situacao de nenhuma
exposicao (baixa exigencia e alto apoio social). CONCLUSOES: Os resultados
fortalecem a hipotese de interacao entre os fatores investigados, com direcao
para a sinergia dos efeitos.
PMID- 28513765
TI - Factors associated with suicidal ideation among university students.
AB - Objective: to analyze the factors associated with suicidal ideation in a
representative sample of university students. Methods: cross-sectional study,
carried out with 637 students of the Federal University of Mato Grosso. The
presence of suicidal ideation, demographic and socioeconomic variables, use of
alcohol through the Alcohol, Smoking and Substance Involvement Screening Test,
and depressive symptoms (Major Depression Inventory) were investigated. Bivariate
analysis was performed with the Chi-square test and multivariate analysis using
the Poisson regression model. Results: it was found that 9.9% of the students had
suicidal thoughts in the previous 30 days and, in the bivariate analysis, the
variables economic class, sexual orientation, religious practice, suicide
attempts in the family and among friends, alcohol consumption and depressive
symptoms were associated with suicidal ideation. In the multivariate analysis
sexual orientation, suicide attempts in the family and the presence of depressive
symptoms remained as associated factors. Conclusion: these findings constitute a
situational diagnosis that enables the formulation of academic policies and
preventive actions to confront this situation on the university campus.
PMID- 28513767
TI - Capnography as a tool to detect metabolic changes in patients cared for in the
emergency setting.
AB - Objective:: to evaluate the usefulness of capnography for the detection of
metabolic changes in spontaneous breathing patients, in the emergency and
intensive care settings. Methods:: in-depth and structured bibliographical search
in the databases EBSCOhost, Virtual Health Library, PubMed, Cochrane Library,
among others, identifying studies that assessed the relationship between
capnography values and the variables involved in blood acid-base balance.
Results:: 19 studies were found, two were reviews and 17 were observational
studies. In nine studies, capnography values were correlated with carbon dioxide
(CO2), eight with bicarbonate (HCO3), three with lactate, and four with blood pH.
Conclusions:: most studies have found a good correlation between capnography
values and blood biomarkers, suggesting the usefulness of this parameter to
detect patients at risk of severe metabolic change, in a fast, economical and
accurate way. Objetivo:: avaliar a utilidade da capnografia para a deteccao de
alteracoes metabolicas em pacientes com respiracao espontanea, no contexto das
emergencias e dos cuidados intensivos. Metodo:: pesquisa bibliografica
estruturada aprofundada, nas bases de dados EBSCOhost, Biblioteca Virtual em
Saude, PubMed, Cochrane Library, entre outras, identificando estudos que
avaliavam a relacao entre os valores da capnografia e as variaveis envolvidas no
equilibrio acido-base sanguineo. Resultados:: foram levantados 19 estudos, dois
eram revisoes e 17 eram estudos observacionais. Em nove estudos, os valores
capnograficos foram correlacionados com o dioxido de carbono (CO2), em oito com o
bicarbonato (HCO3), em tres com o lactato, e em quatro com o pH sanguineo.
Conclusoes:: na maioria dos estudos foi observada uma correlacao adequada entre
os valores capnograficos e os biomarcadores sanguineos, sugerindo a utilidade
deste parametro para a identificacao de pacientes com risco de sofrer uma
alteracao metabolica grave, de uma forma rapida, economica e precisa. Objetivo::
explorar la utilidad de la capnografia para la deteccion de alteraciones
metabolicas ante pacientes en respiracion espontanea, en el ambito de las
emergencias y los cuidados criticos. Metodo:: busqueda bibliografica estructurada
en profundidad, en bases de datos EBSCOhost, Biblioteca Virtual de la Salud,
PubMed, Cochrane Library, entre otras, identificando estudios que evaluaban la
relacion entre valores de la capnografia y variables implicadas en el equilibrio
acido-base sanguineo. Resultados:: se recopilaron 19 estudios, dos eran
revisiones y 17 observacionales. En nueve estudios, se correlacionaron los
valores capnograficos junto al dioxido de carbono (CO2), en ocho con el
bicarbonato (HCO3), tres con el lactato, y cuatro con el pH sanguineo.
Conclusiones:: la mayoria de estudios han obtenido una correlacion adecuada entre
los valores capnograficos y biomarcadores sanguineos, sugiriendo la utilidad de
este parametro para la deteccion de pacientes en riesgo de padecer una alteracion
metabolica grave, de forma rapida, economica y precisa.
PMID- 28513766
TI - Intervening factors for the initiation of treatment of patients with stomach and
colorectal cancer.
AB - Objective: to identify the time between symptoms, the request for care and the
beginning of treatment in patients with stomach and colorectal cancer as well as
the factors that interfere in these processes. Method: correlational descriptive
study, including 101 patients diagnosed with stomach or colorectal cancer,
treated in a hospital specialized in oncology. Results: the 101 patients
investigated there was predominance of males, mean age of 61.7 years. The search
for medical care occurred within 30 days after the onset of symptoms, in most
cases. The mean total time between the onset of symptoms and the beginning of
treatment ranged from 15 to 16 months, and the mean time between the search for
medical care and the diagnosis was 4.78 months. The family history of cancer
(p=0.008) and the implementation of preventive follow-up (p<0.001) were
associated with shorter periods between the search for care and the beginning of
treatment. Nausea, vomiting, hematochezia, weight loss and pain were associated
with faster demand for care. Conclusion: the longer interval between the search
for medical care and the diagnosis was possibly due to the non-association
between the presented symptoms and the disease.
PMID- 28513768
TI - Microbiological testing of devices used in maintaining peripheral venous
catheters.
AB - Objective: to evaluate the use of peripheral venous catheters based on
microbiological analysis of devices (dressing and three-way stopcocks) and thus
contribute to the prevention and infection control. Methods: this was a
prospective study of microbiological analysis of 30 three-way stopcocks (external
surfaces and lumens) and 30 dressing used in maintaining the peripheral venous
catheters of hospitalized adult patients. Results: all external surfaces, 40% of
lumens, and 86.7% of dressing presented bacterial growth. The main species
isolated in the lumen were 50% coagulase-negative Staphylococcus, 14.3%
Staphylococcus aureus, and 14.3% Pseudomonas aeruginosa. Fifty nine percent of
multidrug-resistant bacteria were isolated of the three-way stopcocks, 42% of the
lumens, and 44% of the dressing with a predominance of coagulase-negative
Staphylococcus resistant to methicillin. Besides, 18% gram-negative bacteria with
resistance to carbapenems were identified from multidrug-resistant bacteria on
the external surfaces of the three-way stopcocks. Conclusion: it is important to
emphasize the isolation of coagulase-negative Staphylococcus and gram-negative
bacteria resistant to methicillin and carbapenems in samples of devices,
respectively, which reinforces the importance of nursing care in the maintenance
of the biologically safe environment as well as prevention and infection control
practices.
PMID- 28513769
TI - The situation of nursing education in Latin America and the Caribbean towards
universal health.
AB - Objective:: to assess the situation of nursing education and to analyze the
extent to which baccalaureate level nursing education programs in Latin America
and the Caribbean are preparing graduates to contribute to the achievement of
Universal Health. Method:: quantitative, descriptive/exploratory, cross-sectional
study carried out in 25 countries. Results:: a total of 246 nursing schools
participated in the study. Faculty with doctoral level degrees totaled 31.3%,
without Brazil this is reduced to 8.3%. The ratio of clinical experiences in
primary health care services to hospital-based services was 0.63, indicating that
students receive more clinical experiences in hospital settings. The results
suggested a need for improvement in internet access; information technology;
accessibility for the disabled; program, faculty and student evaluation; and
teaching/learning methods. Conclusion:: there is heterogeneity in nursing
education in Latin America and the Caribbean. The nursing curricula generally
includes the principles and values of Universal Health and primary health care,
as well as those principles underpinning transformative education modalities such
as critical and complex thinking development, problem-solving, evidence-based
clinical decision-making, and lifelong learning. However, there is a need to
promote a paradigm shift in nursing education to include more training in primary
health care. Objetivo:: avaliar a situacao da educacao em enfermagem e analisar o
quanto os programas de educacao em enfermagem, no nivel de Bacharelado na America
Latina e no Caribe, estao preparando graduados a contribuir para o alcance da
Saude Universal. Metodo:: estudo quantitativo, descritivo/exploratorio,
transversal, realizado em 25 paises. Resultados:: um total de 246 escolas de
enfermagem participaram do estudo. O corpo docente com nivel de Doutorado
totalizou 31,3%; sem o Brasil o numero fica reduzido a 8,3%. A razao entre
experiencias clinicas nos servicos de atencao primaria a saude e nos servicos
hospitalares foi de 0,63, indicando que os estudantes tem mais experiencias
clinicas nos cenarios hospitalares. Os resultados sugeriram necessidade de
aprimoramento relacionada ao acesso a Internet; tecnologia da informacao; acesso
para portadores de deficiencias; avaliacao do programa, do corpo docente e dos
estudantes; e aos metodos de ensino/aprendizagem. Conclusao:: ha heterogeneidade
na educacao em enfermagem na America Latina e no Caribe. Os curriculos de
enfermagem incluem, geralmente, os principios e valores da Saude Universal e da
atencao primaria a saude, bem como aqueles principios subjacentes as modalidades
de educacao transformativa, como o desenvolvimento de pensamento critico e
complexo, a solucao de problemas, a tomada de decisao clinica baseada em
evidencias, e aprendizagem continua. No entanto, e preciso promover uma mudanca
de paradigma na educacao em enfermagem que inclua mais treinamento na atencao
primaria a saude. Objetivo:: evaluar la situacion de la educacion en enfermeria y
analizar en que grado los programas de educacion de enfermeria a nivel de grado
en America Latina y el Caribe estan preparando a los graduados para contribuir al
logro de la Salud Universal. Metodo:: se llevo a cabo un estudio transversal,
cuantitativo, descriptivo y exploratorio en 25 paises. Resultados:: participaron
en el estudio 246 escuelas de enfermeria. El porcentaje de profesores con titulos
de doctorado fue de 31,3%; pero, si se excluye a Brasil esta cifra se reduce a
8,3%. La proporcion de la experiencia clinica adquirida en los servicios de
atencion primaria de salud en relacion con la adquirida en servicios
hospitalarios fue de 0,63, lo que indica que los estudiantes adquieren la mayor
parte de su experiencia clinica en entornos hospitalarios. Los resultados
mostraron una necesidad de mejorar el acceso a internet; la tecnologia de la
informacion; la accesibilidad para las personas discapacitadas; la evaluacion de
los programas, de los profesores y de los estudiantes; y los metodos de ensenanza
y aprendizaje. Conclusiones:: hay heterogeneidad en la educacion en enfermeria en
America Latina y el Caribe. En general, los programas de estudios de enfermeria
han adoptado los principios y los valores de la Salud Universal y la atencion
primaria de salud, asi como los principios que sustentan las modalidades de
educacion transformadora, como son el desarrollo del pensamiento critico y
complejo, la solucion de problemas, la toma de decisiones clinicas basadas en la
evidencia y el aprendizaje a lo largo de toda la vida. Sin embargo, hay necesidad
de promover un cambio en el paradigma de la educacion en enfermeria, a fin de que
abarque mas capacitacion en la atencion primaria de salud.
PMID- 28513770
TI - Association between MFN2 gene polymorphisms and the risk and prognosis of acute
liver failure: a case-control study in a Chinese population.
AB - This study aimed to determine the role of mitofusin 2 (MFN2) gene polymorphisms
in the risk and prognosis of acute liver failure (ALF). A total of 298 blood
samples were collected from 138 ALF patients (case group) and 160 healthy
participants (control group). Coagulation function, glutamic pyruvic transaminase
(GPT), glutamic oxaloacetic transaminase (GOT), total bilirubin (TB), blood
ammonia and lactic acid (LA) were measured. The predictive evaluation of MFN2
gene polymorphisms in the risk and prognosis of ALF patients was estimated using
Kaplan-Meier survival analysis, haplotype analysis, binary logistic regression
analysis and Cox regression analysis. Higher levels of GPT, GOT, TB, blood
ammonia and LA were observed in ALF patients with the GG genotype of rs873457 or
the TT genotype of rs4846085 than in those with the CC genotype of these two
SNPs. The GTACAGC and GTGTGGC haplotypes were a protective factor and a risk
factor for ALF, respectively. Blood ammonia and LA levels were independent risk
factors and the CC genotype of rs873457 and the CC genotype of rs4846085 were
protective factors for ALF. ALF patients with the GG genotype of rs873457 or the
TT genotype of rs4846085 had a lower survival rate than those with other
genotypes of these two SNPs. The rs4846085 and rs873457 polymorphisms were both
independent factors affecting the prognosis of ALF patients. MFN2 gene
polymorphisms (rs873457, rs2336384, rs1474868, rs4846085 and rs2236055) may be
associated with ALF and the rs873457 and rs4846085 polymorphisms are correlated
with the risk and prognosis of ALF.
PMID- 28513772
TI - Etanercept protects rat cardiomyocytes against hypertrophy by regulating
inflammatory cytokines secretion and cell apoptosis.
AB - We aimed to investigate the effect of etanercept, a tumor necrosis factor-alpha
(TNF-alpha) inhibitor, on rat cardiomyocyte hypertrophy and its underlying
mechanism. Primary neonatal rat cardiomyocytes were isolated from Sprague-Dawley
rats. The model of rat cardiomyocyte hypertrophy was induced by endothelin, and
then treated with different concentrations of etanercept (1, 10, and 50 MUM).
After treatment, cell counts, viability and cell apoptosis were evaluated. The
mRNA levels of myocardial hypertrophy marker genes, including atrial natriuretic
factor (ANF), matrix metalloproteinase (MMP)-9 and MMP-13, were detected by qRT
PCR, and the expressions of apoptosis-related proteins (Bcl-2 and Bax) were
measured by western blotting. The protein levels of transforming growth factor
beta1 (TGF-beta1), interleukin (IL)-1beta, IL-6, leukemia inhibitory factor (LIF)
and cardiotrophin-1 (CT-1) were determined using enzyme linked immunosorbent
assay (ELISA) kits. In the present study, TNF-alpha level in cardiomyocytes with
hypertrophy was significantly enhanced (P<0.05). Compared to the model group,
cell number and viability were significantly increased and ratio of apoptotic
cells was reduced by etanercept (P<0.05, P<0.01, or P<0.001). In addition,
etanercept remarkably reduced the mRNA levels of ANF, MMP-9 and MMP-13, inhibited
the expression of Bax, and increased the expression of Bcl-2 compared to the
model group (P<0.05). ELISA results further showed that etanercept lowered the
levels of IL-1beta, IL-6, LIF and CT-1 but not TGF-beta1 compared to the model
group (P<0.05). Etanercept may protect rat cardiomyocytes from hypertrophy by
inhibiting inflammatory cytokines secretion and cell apoptosis.
PMID- 28513771
TI - Species distribution and antifungal susceptibility patterns of Candida isolates
from a public tertiary teaching hospital in the Eastern Cape Province, South
Africa.
AB - Candida species are the leading cause of invasive fungal infections, and over the
past decade there has been an increased isolation of drug resistant Candida
species. This study aimed to identify the species distribution of Candida
isolates and to determine their unique antifungal susceptibility and resistance
patterns. During a cross-sectional study, 209 Candida isolates (recovered from
206 clinical samples) were collected and their species distribution was
determined using ChromAgar Candida. The Vitek-2 system (Biomerieux, South Africa)
was used to determine minimum inhibitory concentrations (MICs) to azoles
(fluconazole, voriconazole), echinocandins (caspofungin, micafungin), polyenes
(amphotericin B) and flucytosine. Four species of Candida were isolated, of which
C. albicans was the most frequent, isolated in 45.4% (95/209) of the isolates,
followed by C. glabrata: 31.1% (65/209). The MICs of the different antifungal
drugs varied amongst the species of Candida. From the 130 isolates tested for
MICs, 90.77% (112/130) were susceptible to all antifungal drugs and 6.9% (9/130)
of the isolates were multi-drug resistant. C. dubliniensis (n=2) isolates were
susceptible to all the above mentioned antifungal drugs. There was no significant
difference in species distribution amongst clinical specimens and between
patients' genders (P>0.05). An increase in MIC values for fluconazole and
flucytosine towards the resistance range was observed. To our knowledge, this is
the first report on surveillance of Candida species distribution and antifungal
susceptibility at a public tertiary teaching hospital in Eastern Cape, South
Africa.
PMID- 28513773
TI - Attenuation of renal ischemic reperfusion injury by salvianolic acid B via
suppressing oxidative stress and inflammation through PI3K/Akt signaling pathway.
AB - Salvianolic acid B (SAB) is one the major phytocomponents of Radix Salvia
miltiorrhiza and exhibit numerous health promoting properties. The objective of
the current study was to examine whether SAB exerts a renoprotective effect by
attenuating oxidative stress and inflammatory response through activating
phosphatidylinositol 3-kinase/serine-threonine kinase B (PI3K/Akt) signaling
pathway in a renal ischemic reperfusion rat model. Forty Sprague-Dawley male rats
(250-300 g) were obtained and split into four groups with ten rats in each group.
The right kidney of all rats was removed (nephrectomy). The rats of the Control
group received only saline (occlusion) and served as a sham control group,
whereas rats subjected to ischemic reperfusion (IR) insult by clamping the left
renal artery served as a postitive control group. The other 2 groups of rats were
pretreated with SAB (20 and 40 mg.kg-1.day-1) for 7 days prior IR induction and
served as treatment groups (SAB 20+IR; SAB 40+IR). Renal markers creatinine (Cr)
and blood urea nitrogen (BUN) were significantly lower in the groups that
received SAB. Pretreatment with SAB appears to attenuate oxidative stress by
suppressing the production of lipid peroxidation products like malondialdehyde as
well as elevating antioxidant activity. The concentration of inflammatory markers
and neutrophil infiltration (myeloperoxidase) were significantly decreased.
Meanwhile, PI3K protein expression and pAkt/Akt ratio were significantly
upregulated upon supplementation with SAB, indicating its renoprotective
activity. Taken together, these results indicate that SAB can therapeutically
alleviate oxidative stress and inflammatory process via modulating PI3K/Akt
signaling pathway and probably ameliorate renal function and thus act as a
renoprotective agent.
PMID- 28513774
TI - Hippocampal overexpression of Down syndrome cell adhesion molecule in amyloid
precursor protein transgenic mice.
AB - Down syndrome cell adhesion molecule (DSCAM) is located within the Down syndrome
critical region of chromosome 21. DSCAM is a broadly expressed neurodevelopmental
protein involved in synaptogenesis, neurite outgrowth, and axon guidance. We
previously demonstrated DSCAM overexpression in the cortex of amyloid precursor
protein (APP) transgenic mice, suggesting possible regulatory interactions
between APP and DSCAM. APP mice exhibit deficits in hippocampus-dependent
learning and memory. In this preliminary study, we examined age-related changes
in DSCAM expression within the hippocampus in 16 APP transgenic mice (1, 3, 6 and
12 months old). Hippocampus-dependent spatial memory was assessed in APP mice and
age-matched wild type littermates (WTs) using the Morris water maze (MWM). The
cellular distribution of hippocampal DSCAM and total expression at both mRNA and
protein levels were measured by immunohistochemistry, qRT-PCR, and western
blotting, respectively. APP mice exhibited spatial memory deficits in the MWM.
Intense DSCAM immunoreactivity was observed in the dentate gyrus granule cell
layer and hippocampal stratum pyramidale. Total hippocampal DSCAM mRNA and
protein expression levels were substantially higher in APP mice than WTs at 1 and
3 months of age. Expression decreased with age in both groups but remained higher
in APP mice. DSCAM is overexpressed in the hippocampus over the first 12 months
of life in APP mice, but especially during maturation to adulthood. In
conclusion, these results suggest an association between DSCAM and APP mice,
which is characterized by neuropathology and behavioral deficits. These results
provide some clues for future studies on the role of DSCAM overexpression in the
precocious cognitive decline observed in APP transgenic mice.
PMID- 28513776
TI - CHARACTERIZATION AND INFLUENCE OF SUBTROPICAL PERSIMMON CULTIVARS ON JUICE AND
JELLY CHARACTERISTICS.
AB - To increase the availability to consumers and add more value to persimmon
(Diospyros kaki L.), which is a very perishable and seasonal fruit and in order
to identify which cultivars grown in subtropical regions are more suitable for
processing in the form of juice and jelly, as well as understand what the
consumer profile is for these products, the objective of this study was to
evaluate the influence of different persimmon cultivars (Rama Forte, Mel, Guiombo
and Taubate) grown in subtropical regions of Brazil on the physicochemical
characteristics, rheological properties and sensory acceptance of the resulting
juice and jelly in order to identify cultivars with the greatest potential for
industrial use. The different studied persimmon cultivars had different physical
and physicochemical characteristics which resulted in juices and jellies with
different physicochemical, rheological and sensory characteristics. Based on
sensory acceptance and productivity/adaptability of persimmon crop in Brazil, the
most suitable persimmon cultivars for processing are Rama Forte and Guiombo. In
this study it was found that the consumer prefers a more acidic persimmon juice
and a less firm or softer, less sweet, clearer and more intense yellow color
persimmon jelly.
PMID- 28513775
TI - Adiponectin inhibits oxidization-induced differentiation of T helper cells
through inhibiting costimulatory CD40 and CD80.
AB - Adiponectin is a multifunctional adipokine that has several oligomeric forms in
the blood stream, which broadly regulates innate and acquired immunity.
Therefore, in this study, we aimed to observe the differentiation of T helper
(Th) cells and expression of costimulatory signaling molecules affected by
adiponectin. The mRNA and protein expression levels of adiponectin and its
receptors in oxidized low density lipoprotein cholesterol-treated endothelial
cells were assayed by real time PCR and immunofluorescence. The endothelial cells
were then treated with adiponectin with or without adipoR1 or adipoR2 siRNA and
co-cultured with T lymphocytes. The distribution of Th1, Th2 and Th17 subsets
were assayed by flow cytometry. The effects of adiponectin on costimulatory
signaling molecules HLA-DR, CD80, CD86 and CD 40 was also assayed by flow
cytometry. The results showed that endothelial cells expressed adiponectin and
its receptor adipoR1 and adipoR2, but not T-cadherin. Adiponectin suppressed Th1
and Th17 differentiation through adipoR1 receptor, contributed to the inhibition
of CD80 and CD40, and inhibited differentiation of Th1 and Th17 by inhibiting
antigen presenting action.
PMID- 28513777
TI - Population dynamics of Siderastrea stellata Verrill, 1868 from Rocas Atoll, RN:
implications for predicted climate change impacts at the only South Atlantic
atoll.
AB - Coral reefs are one of the most vulnerable ecosystems to ocean warming and
acidification, and it is important to determine the role of reef building species
in this environment in order to obtain insight into their susceptibility to
expected impacts of global changes. Aspects of the life history of a coral
population, such as reproduction, growth and size-frequency can contribute to the
production of models that are used to estimate impacts and potential recovery of
the population, acting as a powerful tool for the conservation and management of
those ecosystems. Here, we present the first evidence of Siderastrea stellata
planulation, its early growth, population size-frequency distribution and growth
rate of adult colonies in Rocas Atoll. Our results, together with the
environmental protection policies and the absence of anthropogenic pressures,
suggest that S. stellata population may have a good potential in the maintenance
and recovery in the atoll. However, our results also indicate an impact on
corals' recruitment, probably as a consequence of the positive temperature
anomaly that occurred in 2010. Thus, despite the pristine status of Rocas Atoll,
the preservation of its coral community seems to be threatened by current global
changes, such as more frequent thermal stress events.
PMID- 28513779
TI - The preventive effects of ascorbic acid supplementation on locomotor and
acetylcholinesterase activity in an animal model of schizophrenia induced by
ketamine.
AB - Studies have shown that schizophrenic patients seem to have nutritional
deficiencies. Ascorbic acid (AA) has an important antioxidant effect and
neuromodulatory properties. The aim of this study was to evaluate the effects of
AA on locomotor activity and the acetylcholinesterase activity (AChE) in an
animal model of schizophrenia (SZ). Rats were supplemented with AA (0.1, 1, or 10
mg/kg), or water for 14 days (gavage). Between the 9th and 15th days, the animals
received Ketamine (Ket) (25 mg/kg) or saline (i.p). After the last administration
(30 min) rats were subjected to the behavioral test. Brain structures were
dissected for biochemical analysis. There was a significant increase in the
locomotor activity in Ket treated. AA prevented the hyperlocomotion induced by
ket. Ket also showed an increase of AChE activity within the prefrontal cortex
and striatum prevented by AA. Our data indicates an effect for AA in preventing
alterations induced by Ket in an animal model of SZ, suggesting that it may be an
adjuvant approach for the development of new therapeutic strategies within this
psychiatric disorder.
PMID- 28513780
TI - Reduction of the DNA damages, Hepatoprotective Effect and Antioxidant Potential
of the Coconut Water, ascorbic and Caffeic Acids in Oxidative Stress Mediated by
Ethanol.
AB - Hepatic disorders such as steatosis and alcoholic steatohepatitis are common
diseases that affect thousands of people around the globe. This study aims to
identify the main phenol compounds using a new HPLC-ESI+-MS/MS method, to
evaluate some oxidative stress parameters and the hepatoprotective action of
green dwarf coconut water, caffeic and ascorbic acids on the liver and serum of
rats treated with ethanol. The results showed five polyphenols in the lyophilized
coconut water spiked with standards: chlorogenic acid (0.18 uM), caffeic acid
(1.1 uM), methyl caffeate (0.03 uM), quercetin (0.08 uM) and ferulic acid (0.02
uM) isomers. In the animals, the activity of the serum gamma
glutamyltranspeptidase (gamma-GT) was reduced to 1.8 I.U/L in the coconut water
group, 3.6 I.U/L in the ascorbic acid group and 2.9 I.U/L in the caffeic acid
groups, when compared with the ethanol group (5.1 I.U/L, p<0.05). Still in liver,
the DNA analysis demonstrated a decrease of oxidized bases compared to ethanol
group of 36.2% and 48.0% for pretreated and post treated coconut water group
respectively, 42.5% for the caffeic acid group, and 34.5% for the ascorbic acid
group. The ascorbic acid was efficient in inhibiting the thiobarbituric acid
reactive substances (TBARS) in the liver by 16.5% in comparison with the ethanol
group. These data indicate that the green dwarf coconut water, caffeic and
ascorbic acids have antioxidant, hepatoprotective and reduced DNA damage
properties, thus decreasing the oxidative stress induced by ethanol metabolism.
PMID- 28513781
TI - Mitochondria-rich cells changes induced by nitrite exposure in tambaqui
(Colossoma macropomum Cuvier, 1818).
AB - The gill mitochondria-rich cells of the juvenile Amazonian fish Colossoma
macropomum were analyzed using light and scanning and transmission electron
microscopy after 96 h exposure to 0.04 and 0.2 mM nitrite. Although the number of
mitochondria-rich cells decreased significantly in the lamellar epithelium, no
decrease was found in the interlamellar region of the gill filament. Nitrite
exposure caused significant reduction on the apical surface area of individual
mitochondria-rich cells (p < 0.05), with a resulting reduction of the fractional
area of these cells in both the lamellar and filament epithelium. Swelling of
endoplasmic reticulum cisternae, nuclear envelope and mitochondria were the main
changes found in the mitochondria-rich cells. Cristae lysis and matrix
vacuolization characterized the mitochondrial changes. The overall
ultrastructural changes indicated cellular functional disruption caused by
exposure to nitrite. The changes observed in the gill indicate that the cellular
structures involved in the process of energy production become severely damaged
by exposure to nitrite indicating irreversible damage conducting to cell death.
PMID- 28513782
TI - Soil-vegetation relationships and community structure in a "terra-firme"-white
sand vegetation gradient in Virua National Park, northern Amazon, Brazil.
AB - Virua National Park encompasses a vast and complex system of hydromorphic sandy
soils covered largely by the white sand vegetation ("Campinarana") ecosystem. The
purpose of this study was to investigate a vegetation gradient of "terra-firme"
white sand vegetation at the Virua National Park. Nine plots representing three
physiognomic units were installed for floristic and phytosociological surveys as
well as to collect composite soil samples. The data were subjected to assessments
of floristic diversity and similarity, phytosociological parameters and to
statistical analyses, focused on principal components (PC) and canonical
correspondence analysis (CCA). The vegetation of the Campinaranas types and
Forest differed in biomass and species density. Ten species, endemic to Brazil,
were particularly well-represented. PC and CCA indicated a clear distinction
between the studied plots, based on measured soil variables, especially base sum
and clay, which were the most differentiating properties between Campinarana and
Forest; For the separation of the Campinarana types, the main distinguishing
variable was organic matter content and cation exchange capacity. Higher
similarity of Campinaranas was associated to a monodominant species and the lower
similarity of Forest was related to the high occurrence of locally rare species.
PMID- 28513784
TI - Chlorhexidine with or without alcohol against biofilm formation: efficacy,
adverse events and taste preference.
AB - In recent years, different chlorhexidine formulations have been tested, including
an alcohol-free alternative, but the effect of this solution on early biofilm
formation is not clear. A crossover, randomized, double-blind clinical trial was
conducted to evaluate the effect of two chlorhexidine solutions against supra-
and subgingival biofilm formation (NCT#02656251). Thirty-five participants were
randomized and asked to rinse twice daily with 15 ml of an alcohol-containing
0.12% chlorhexidine solution, an alcohol-free 0.12% chlorhexidine solution, or
placebo. The study was conducted in three experimental periods of 4 days each,
with a 10-day washout between the periods. All the experimental periods followed
the same protocol, except that the solutions were switched. Biofilm distribution
was evaluated every 24 hours by the Plaque-Free Zone Index, during 96 hours.
Adverse events were self-reported and sensory evaluation was performed using a
hedonic scale. Compared to the placebo, the chlorhexidine solutions resulted in a
significantly higher number of surfaces free of plaque over 96 hours (p < 0.01),
and were able to prevent subgingival biofilm formation (p < 0.01). The alcohol
free chlorhexidine solution was associated with a lower incidence of adverse
events, compared with alcohol-containing chlorhexidine (p < 0.05); it also
received better sensory evaluation and acceptance by trial participants, compared
with the alcohol-containing chlorhexidine (p = 0.007), and had a similar
inhibitory effect on the formation of supra- and subgingival biofilms.
PMID- 28513783
TI - Influence of addition of [2-(methacryloyloxy)ethyl]trimethylammonium chloride to
an experimental adhesive.
AB - The aim of this study was to develop an experimental adhesive with addition of [2
(methacryloyloxy)ethyl]trimethylammonium chloride (METAC) and to evaluate its
mechanical and biological properties and its in vitro antibacterial activity. An
experimental adhesive resin was formulated with Bis-GMA, TEGDMA, and HEMA. The
antibacterial monomer was added at concentrations of 1%, 2.5%, and 5% (METAC
groups). A group without METAC addition was used as control. The experimental
adhesives were evaluated as to their antibacterial potential against
Streptococcus mutans, degree of conversion, and softening in ethanol for 2 hours.
The data were analyzed by one-way ANOVA, Tukey's post-hoc test, and the paired
Student's t-test (significance level of 0.05). METAC showed antibacterial
activity against S. mutans at all concentrations (p < 0.05). There was no
statistical difference across METAC groups (p > 0.05). The 1%, 2.5%, and 5%
groups yielded the highest mean values for degree of conversion (p < 0.05). The
1% group did not differ from the control group (p > 0.05). There was no
statistical difference in baseline microhardness values (p > 0.05) and
microhardness values after immersion in ethanol were lower than at baseline for
all groups (p < 0.05). There was no statistical difference in the reduction of
Knoop hardness number (KHN) after immersion in ethanol for any of the groups (p >
0.05). The results of the present study indicate that METAC is a promising
antibacterial agent when added to an adhesive system.
PMID- 28513785
TI - Microbiological outcomes from different periodontal maintenance interventions: a
systematic review.
AB - This study aimed to investigate the differences in the subgingival
microbiological outcomes between periodontal patients submitted to a
supragingival control (SPG) regimen as compared to subgingival scaling and root
planing performed combined with supragingival debridement (SPG + SBG)
intervention during the periodontal maintenance period (PMP). A systematic
literature search using electronic databases (MEDLINE and EMBASE) was conducted
looking for articles published up to August 2016 and independent of language. Two
independent reviewers performed the study selection, quality assessment and data
collection. Only human randomized or non-randomized clinical trials with at least
6-months-follow-up after periodontal treatment and presenting subgingival
microbiological outcomes related to SPG and/or SPG+SBG therapies were included.
Search strategy found 2,250 titles. Among these, 148 (after title analysis) and
39 (after abstract analysis) papers were considered to be relevant. Finally, 19
studies were selected after full-text analysis. No article had a direct
comparison between the therapies. Five SPG and 14 SPG+SBG studies presented
experimental groups with these respective regimens and were descriptively
analyzed while most of the results were only presented graphically. The results
showed that both SPG and SPG+SBG protocols of PMP determined stability in the
microbiological results along time. Nevertheless, new studies comparing these
interventions in PMP are needed, especially if the limitations herein discussed
could be better controlled.
PMID- 28513787
TI - Does the trait anxiety affect the dental fear?
AB - The aims of the present study were to evaluate possible associations between
trait anxiety, dental fear and the predictors of these interactions including
demographic characteristics and dental history of patients applied to the dental
care center in Ankara, Turkey. A sample of 607 participants (mean age: 21.02 +/-
2.32) responded to a Turkish version of the Modified Dental Fear Survey (MDFS),
the State-Trait Anxiety Inventory (STAI-T) and a questionnaire regarding previous
negative dental experience. Multiple logistic regression analysis was used to
identify the association between dental fear and the independent variables
including trait anxiety, age groups, education level, dental visit frequency,
experience and the source of dental knowledge. There was a trend for increasing
in trait anxiety scores with greater levels of dental fear in a medium level of
the dental fear group (OR = 1.055, 95%CI [1.025-1.086]; p < 0.001) and in a high
level of the dental fear group (OR = 1.090 [1.057-1.124]; p < 0.001). Comparing
to the low level of dental fear group; participants of medium dental fear level
intended more likely to go to the dentist when they have a complaint instead of
regularly going (odds ratio; OR = 3.177, 95%CI [1.304-7.741]; p = 0.011).
Participants of high dental fear level tended to be less likely to have
experienced no problem (OR = 0.476, 95%CI [0.284-0.795]; p = 0.005) than the low
level of the dental fear group. We strongly indicate that higher dental fear
scores have a predisposition of having high trait anxiety scores. Unpleasant
dental experiences increased the risk for high dental fear levels. Patients with
dental fear tended only to visit a dentist when necessary, avoiding regular
visits.
PMID- 28513786
TI - 3-year survival rates of retained composite resin and ART sealants using two
assessment criteria.
AB - The aim was to test the null-hypothesis that there is no difference in the
cumulative survival rate of retained composite resin (CR) sealants and a high
viscosity glass-ionomer Atraumatic Restorative Treatment (ART) sealant in first
permanent molars calculated according to the traditional and the modified
retention assessment criteria over a period of 3 years. This cluster-randomized
controlled clinical trial consisted of 123 schoolchildren, 6-7-years-old. At
baseline, high-caries risk pits and fissures of fully erupted first permanent
molars were treated with CR and ART sealants. Evaluations were performed after
0.5, 1, 2 and 3 years. Retention was scored for free-smooth surface and for each
of three sections into which the occlusal surface had been divided. The modified
criterion differed from the traditional in that it determined an occlusal sealant
to be a failure when at least one section contained no visible sealant material.
Data were analysed according to the PHREG model with frailty correction, Wald
test, ANOVA and t-test, using the Jackknife procedure. The cumulative survival
rates for retained CR and ART sealants in free-smooth and occlusal surfaces for
both criteria were not statistically significantly different over the 3 years. A
higher percentage of retained CR sealants on occlusal surfaces was observed at
longer evaluations. Cumulative survival rates were statistically significantly
lower for the modified criterion in comparison to the traditional. The modified
retention assessment criterion should be used in future sealant-retention
studies.
PMID- 28513788
TI - Comparisons of IgA response in saliva and colostrum against oral streptococci
species.
AB - The present study compared IgA specificity against oral streptococci in colostrum
and saliva samples. Sixty-two mother-and-child pairs were included; samples of
colostrum (C) and saliva (MS) were collected from the mothers and saliva samples
were collected from babies (BS). The specificity of IgA against Streptococcus
mutans and S. mitis were analyzed by western blot. Only 30% of babies' samples
presented IgA reactivity to S. mutans, while 74 and 80% of MS and C,
respectively, presented this response. IgA reactivity to S. mutans virulence
antigens (Ag I/II, Gtf and GbpB) in positive samples showed differences between
samples for Gtf and especially for GbpB (p < 0.05), but responses to Ag I/II were
similar (p > 0.05). The positive response of Gtf-reactive IgA was different
between C (90%) and MS (58%) samples (p < 0.05), but did not differ from BS (p >
0.05). GbpB was the least detected, with 48 and 26% of C and MS, and only 5% of
BS samples presenting reactivity (p > 0.05). Eight percent of MS and C samples
presented identical bands to SM in the same time-point. In conclusion, the
differences of IgA response found between C and MS can be due to the different
ways of stimulation, proliferation and transportation of IgA in those secretions.
The colostrum has high levels of IgA against S. mutans virulence antigens, which
could affect the installation and accumulation process of S. mutans, mainly by
supplying anti-GbpB IgA to the neonate.
PMID- 28513789
TI - Effect of final irrigation protocols on microhardness reduction and erosion of
root canal dentin.
AB - This study aimed to evaluate the effect of final irrigation protocols on
microhardness reduction and erosion of root canal dentin. Sixty root canals from
mandibular incisors were instrumented and randomly divided into six groups (n =
10) according to the irrigant used: QMiX, 17% EDTA, 10% citric acid (CA), 1%
peracetic acid (PA), 2.5% NaOCl (solution control), and distilled water (negative
control). The chelating solutions were used to irrigate the canal followed by
2.5% NaOCl as a final flush. After the irrigation protocols, all specimens were
rinsed with 10 mL of distilled water to remove any residue of the chemical
solutions. Before and after the final irrigation protocols, dentin microhardness
was measured with a Knoop indenter. Three indentations were made at 100 um and
500 um from the root canal lumen. Afterwards, the specimens were prepared for
scanning electron microscopic analysis and the amount of dentin erosion was
examined. Wilcoxon and Kruskal-Wallis tests were used to analyze the results with
a significance level set at 5%. At 100 um, all protocols significantly reduced
dentin microhardness (p < .05), while at 500 um, this effect was detected only in
the EDTA and QMiX groups (p < .05). CA was the irrigant that caused more
extensive erosion in dentinal tubules, followed by PA and EDTA. QMiX opened
dentinal tubules, but did not cause dentin erosion. Results suggest that QMiX and
17% EDTA reduced dentin microhardness at a greater depth. Additionally, QMiX did
not cause dentin erosion.
PMID- 28513791
TI - The prevalence of diabetes mellitus and its associated factors in the Brazilian
adult population: evidence from a population-based survey.
AB - Objective:: To estimate the prevalence of self-reported diabetes mellitus (DM)
and its associated factors among the Brazilian adult population. Methods:: The
prevalence of DM was assessed in the Survey on Social Dimensions of Inequalities,
a national survey with macro-regions representativeness carried out in 2008. Data
were collected by a personal face-to-face interview with 12,423 individuals of
both sexes, aged over 20 years. The chi2 test at 5.0% was performed in order to
identify associated factors, and logistic regression was used to estimate
adjusted odds ratios. Results:: The prevalence of DM in Brazil was 7.5%. After
adjusting for potential confounders, diabetes remained associated with age (>= 40
years), education (< 8 years of study), marital status (non-married), obesity,
sedentary lifestyle, comorbidity with hypertension and hypercholesterolemia, as
well as the demand for health services. Conclusion:: Results indicate a high
prevalence of DM and its associated preventable factors in Brazil. Thus, they
highlight the need for a behavioral change as a strategy for prevention and
control of diabetes and its complications.
PMID- 28513790
TI - [Sanitation and racial inequality conditions in urban Brazil: an analysis focused
on the indigenous population based on the 2010 Population Census].
AB - Objective:: The aims of this study were to analyze and describe the presence and
infrastructure of basic sanitation in the urban areas of Brazil, contrasting
indigenous with non-indigenous households. Methods: A cross-sectional study based
on microdata from the 2010 Census was conducted. The analyses were based on
descriptive statistics (prevalence) and the construction of multiple logistic
regression models (adjusted by socioeconomic and demographic covariates). The
odds ratios were estimated for the association between the explanatory variables
(covariates) and the outcome variables (water supply, sewage, garbage collection,
and adequate sanitation). The statistical significance level established was 5%.
Results:: Among the analyzed services, sewage proved to be the most precarious.
Regarding race or color, indigenous households presented the lowest rate of
sanitary infrastructure in Urban Brazil. The adjusted regression showed that, in
general, indigenous households were at a disadvantage when compared to other
categories of race or color, especially in terms of the presence of garbage
collection services. These inequalities were much more pronounced in the South
and Southeastern regions. Conclusion:: The analyses of this study not only
confirm the profile of poor conditions and infrastructure of the basic sanitation
of indigenous households in urban areas, but also demonstrate the persistence of
inequalities associated with race or color in the country.
PMID- 28513792
TI - Evaluation of the Brazilian population's intake of antioxidant nutrients and
their relation with the nutritional status.
AB - Introduction:: The study of dietary antioxidants has gained prominence owing to
the elucidation of the deleterious effects of oxidative stress to the human body.
Objective: To evaluate the Brazilian population's intake of antioxidant nutrients
and their association with the nutritional status. Methods:: A cross-sectional
study was carried out including secondary data on food consumption of 33,459
individuals from both sexes, aged 10 years or older, from all Brazilian regions
based on microdata of the "2008-2009 Household Budget Survey, Brazilian Dairy
Survey." The content of vitamins E, A, and C; zinc; manganese; copper; and
selenium from 188 food items, divided into 12 groups, according to the habitual
consumption form was analyzed. The means of antioxidant nutrient intake according
to the nutritional status were compared using Bonferroni's t-test. Results::
Higher percentages of insufficient intake of vitamins than antioxidant minerals
were seen. A significant difference in the intake of vitamin E as to the
nutritional status was noticed, wherein the intake in overweight individuals was
lower than in those with proper weight. Participants with low weight presented
lower intake of almost all antioxidant minerals, except for copper, in which the
intake of participants with low weight was equal to those with normal weight.
Conclusion:: High percentages of insufficient intake of antioxidant nutrients
were observed in the studied population, especially vitamins. It was also found
that the intake of antioxidant nutrients varied based on nutritional status,
gender, and life stage.
PMID- 28513793
TI - Social inequalities in the prevalence of common mental disorders in adults: a
population-based study in Southern Brazil.
AB - Objective:: This study aimed to investigate the prevalence and factors associated
with Common Mental Disorders (CMD) in adults in a capital city in Southern
Brazil. Methods:: Population-based survey conducted on 1,720 adults aged 20 - 59
years from Florianopolis, Southern Brazil. The CMD were investigated through the
Self-Reporting Questionnaire (SRQ-20). The independent variables were
demographic, socioeconomic, health-related behaviors, health conditions and use
of health services. Multivariable Poisson regression was used for the estimation
of prevalence ratios (PR) and 95%CI. Results:: The prevalence of CMD was 14.7%.
Adjusted analyses showed that the prevalence was higher among women, those self
reported as blacks, with lower educational level, poor,
divorced/separated/widowed, inactive in leisure time, heavy smokers, people with
chronic diseases, those who reported negative health self-rating, those who had
medical appointments and who were hospitalized before the interview. Conclusion::
CMD is relatively high among population subgroups most vulnerable to social
inequalities and with worse conditions related to health indicators.
PMID- 28513794
TI - Psychotropic drug use among older adults: prevalence and associated factors.
AB - Objective:: Investigating the prevalence of psychotropic drug use among older
adults and factors associated with it. Methods:: This study was based on the Belo
Horizonte Metropolitan Area Health Survey, conducted in 2003. It involved 1,635
elderly (60 years or older) citizens, who were residents of cities within the
Belo Horizonte Metropolitan Area and were selected using complex randomize
sampling. Logistic regression models were used to identify factors associated
with psychotropic drug use, with a 5.0% significance level. Results:: The
prevalence of psychotropic drug use in the sample was 13.4%; specifically, 8.3%
of individuals surveyed used benzodiazepines, whereas 5.0% used antidepressants.
The following factors were independently associated with the use of psychotropic
drugs: female gender (OR = 2.20; 95%CI 1.49 - 3.27), medical diagnosis of
depression (OR = 6.42; 95%CI 4.31 - 9.55), 5 or more medical appointments in the
last 12 months (OR = 2.15; 95%CI 1.32 - 3.53), and subscription to private health
insurance (OR = 2.69; 95%CI 1.86 - 3.88). Conclusion:: The prevalence observed
was similar to the one verified in other elderly Brazilian populations and the
pattern of associated factors was consistent with the one detected for older
populations of higher-income countries. Medical diagnosis of depression was the
factor most strongly associated with psychotropic drug use.
PMID- 28513795
TI - Balance of macronutrient intake among Brazilian elderly: analysis of the National
Dietary Survey 2008-2009.
AB - Objective:: This study aimed at evaluating the balance in the intake of protein,
carbohydrate, and fat among the Brazilian elderly population. Methods:: The data
analyzed were taken from the National Dietary Survey 2008-2009, from a total of
4,286 Brazilian elders (60-104 years old). Based on the dietary intake obtained
from two food records, the Multiple Source Method (MSM) was used to evaluate the
macronutrients and saturated fat. The AMDR (Acceptable Macronutrient Distribution
Range), by the Institute of Medicine (IOM), was used to evaluate the
macronutrient energy percentage (%E). Linear regression models identified
differences between macronutrients %E and household location (urban or rural),
Brazilian macro-regions and gender. Results:: Protein intake showed higher
agreement with the AMDR reference value (99.86%). It was observed that in 9.2% of
the population, fat intake was higher than the reference value, almost twice as
high as the carbohydrate-energy percentage (4.9%) and nine times higher than
protein (1.0%). Among those with low carbohydrate-energy percentage, 14.5% had
higher fat-energy percentage (beta = 8.19; p < 0.001), which means that 50% of
the elderly whose carbohydrate intake was above the recommendation presented an
overconsumption of fat. According to the macro-regions, the Midwest region was
the only one to show differences for carbohydrate-energy percentage, which was
lower than the others regions (51.6%; p < 0.05). The South region presented the
lowest protein-energy percentage (17.9%; p < 0.01) and the highest fat-energy
percentage (28.7%; p < 0.01). Conclusion:: Higher prevalence of inadequate fat
intake among the Brazilian elderly may indicate an important public health
problem that is associated with an increased risk of chronic diseases.
PMID- 28513796
TI - Adequacy of sphygmomanometer cuff to brachial circumference of people attended in
Primary Health Care Centers.
AB - Objective:: To evaluate the adequacy of sphygmomanometer cuff to brachial
circumference (BC) of individuals treated at Primary Health Care Centers.
Methods:: Epidemiological, observational, and quantitative cross-sectional study.
A total of 381 blood pressure (BP) readings conducted by nursing professionals
were observed at 18 service units selected by drawing, considering two modalities
of care centers. The correct use of the cuff was the main outcome variable. The
BC was measured using inelastic measuring tape. The tests used for statistical
analysis were Student's t-test, chi2, or Fisher's exact test. Results:: The
measurement of BC ranged from 19.5 to 45.0 cm (mean = 30.4; standard deviation -
SD = 4.3). Among the BP measurements, 218 (57.2%) of them were conducted with the
appropriately sized cuff, being more frequent in the units with Family Health
Teams (59.6 versus 40.4; p < 0.001). Ninety-three (24.2%) BC measurements were <
27 cm and 63 (16.5%) were > 34 cm. The adult cuff was used correctly 209 (59.4%)
times and the large adult cuff was used correctly 9 (31.0%) times. Conclusion::
The study found an inadequacy in the use of the cuff in 42.8% of blood pressure
readings in the Primary Health Care Centers. Similar studies should be performed
in other cities and areas to estimate the effect of this problem in the diagnosis
and monitoring of systemic arterial hypertension (SAH).
PMID- 28513797
TI - Oral health self-perception in quilombola communities in Rio Grande do Sul: a
cross-sectional exploratory study.
AB - Objective:: There's a shortage of evidence on the oral health of quilombolas.
This study aims to describe oral health self-perception, as well as to verify its
associated factors in quilombola communities in the state of Rio Grande do Sul.
Methods:: The data for this cross-sectional health survey were collected by
application of a questionnaire. Since this study was part of a survey on
nutritional security, the probabilistic cluster sample was estimated for the
outcome of nutritional insecurity, comprising 583 individuals across quilombola
communities in Rio Grande do Sul. The association between the outcome of negative
oral health self-perception and sociodemographic, general health, and oral health
variables was measured by prevalence ratios obtained through Poisson regressions
with robust variance and 95% confidence intervals. Results: : Negative self-rated
oral health was reported by 313 (53.1%) of the individuals. Satisfaction with
chewing ability and satisfaction with oral appearance were associated with a
higher prevalence of negative perception of oral health, while there was no
association between the outcome and number of teeth. Use of alcohol had a
borderline association with the outcome. Conclusion:: Satisfaction with
appearance and chewing ability are factors associated with oral-health self
perception of the quilombolas in Rio Grande do Sul.
PMID- 28513798
TI - Anemia and hemoglobin levels among Indigenous Xavante children, Central Brazil.
AB - Objective:: To evaluate the prevalence of anemia, mean hemoglobin levels, and the
main nutritional, demographic, and socioeconomic factors among Xavante children
in Mato Grosso State, Brazil. Methods:: A survey was conducted with children
under 10 years of age in two indigenous Xavante communities within the Pimentel
Barbosa Indigenous Reserve. Hemoglobin concentration levels, anthropometric
measurements, and socioeconomic/demographic data were collected by means of
clinical measurements and structured interviews. The cut-off points recommended
by the World Health Organization were used for anemia classification. Linear
regression analyses with hemoglobin as the outcome and Poisson regression with
robust variance and with the presence or absence of anemia as outcomes were
performed (95%CI). Results:: Lower mean hemoglobin values were observed in
children under 2 years of age, without a significant difference between sexes.
Anemia was observed among 50.8% of children overall, with the highest prevalence
among children under 2 years of age (77.8%). Age of the child was inversely
associated with the occurrence of anemia (adjusted PR = 0.60; 95%CI 0.38-0.95)
and mean hemoglobin values increased significantly with age. Greater height-for
age z-score values reduced the probability of having anemia by 1.8 times
(adjusted PR = 0.59; 95%CI 0.34-1.00). Presence of another child with anemia
within the household increased the probability of the occurrence of anemia by
52.9% (adjusted PR = 1.89; 95%CI 1.16-3.09). Conclusion:: Elevated levels of
anemia among Xavante children reveal a disparity between this Indigenous
population and the national Brazilian population. Results suggest that anemia is
determined by complex and variable relationships between socioeconomic,
sociodemographic, and biological factors.
PMID- 28513799
TI - Energy and nutrient intake according to away-from-home food consumption in the
Northeast Region: an analysis of the 2008-2009 National Dietary Survey.
AB - Introduction:: Away-from-home food consumption has increased in Brazil and is
associated with fewer nutritious food choices. Objective:: To describe energy and
specific nutrient intake among consumers and non-consumer of away-from-home food
in the Northeast Region. Methods:: A sample of 11,674 individuals from the
National Dietary Survey data, which is part of the 2008-2009 Household Budget
Survey, from the Northeast Region, was analyzed. Individuals provided two dietary
records in nonconsecutive days, informing the place where foods were consumed (at
home or away-from-home). Away-from-home food was defined as foods acquired and
consumed away from home. Linear regression models were developed to assess the
relationship between away-from-home food consumption in one of the two-day food
record and the energy and nutrient intake, adjusted for age, gender, and per
capita income. Results:: Away-from-home food consumption, in at least one of the
two-day food record, was reported by 42% of individuals in the Northeast Region.
Individuals who consumed food away from home in the Northeast Region presented
poor nutrient intake compared to those who did not report consumption away from
home, with higher intake of energy, free sugar, saturated fat, and trans fat and
lower intake of protein, iron, and dietary fiber, regardless of age, gender, and
income (p < 0.05). Conclusion:: Away-from-home food consumption in the Northeast
Region contributed to higher energy and poorer nutrient intake. Therefore, the
development of public policies and strategies that favor health food choices when
individuals eat away from home is necessary.
PMID- 28513800
TI - Sociodemographic factors and functional capacity of elderly affected by stroke.
AB - Introduction:: Diseases of old age have shown increasing prevalence in society.
One of them is stroke, which can be conceptualized as the interruption of
cerebral blood supply due to a leakage or blood vessel obstruction caused by
clots. Objective:: To verify the associations between sociodemographic factors
and the functional capacity of elderly affected by stroke. Methods:: This is an
epidemiological, cross-sectional, and quantitative study, including 118 elderly
people with paralyses due to stroke, who were registered in one of the Family
Health Strategies units of Campina Grande, Paraiba, Brazil. Data were collected
by means of home interviews. Two questionnaires were used, in which one was
directed for assessment of sociodemographic variables and the second was called
Barthel index for assessing the functional capacity of the subjects regarding the
activities of daily life. The analysis was conducted using the statistical
program SPSS. Results:: There was a predominance of the female gender, widowed,
without schooling, and with household income of up to one Brazilian minimum wage.
The average age was 65 years (+/- 9.63). The Barthel index internal consistency
was satisfactory, presenting values of Cronbach's alpha coefficient in the range
of 0.897-0.918. Total correlation of corrected items was greater than 0.4, and
Cronbach's alpha with a deleted item was also greater than 0.8. The activities
with higher level of achievement difficulty were urination and evacuation.
Association between functional capacity with race, age range, and schooling was
found. Conclusion:: It was seen that demographic factors might interfere with the
functional capacity of elderly affected by stroke. Hence, it is believed that
this investigation might have contributed to the reflection on this issue, thus
supporting the promotion of these people's access to health assistance programs.
PMID- 28513801
TI - Validity and reliability of a telephone survey of physical activity in Brazil.
AB - Introduction:: Physical activity in Brazil is assessed by the Telephone-based
Risk Factor Surveillance System for Chronic Diseases (VIGITEL). Objectives:: To
evaluate the reliability and concurrent validity of VIGITEL physical activity
indicators. Methods:: For the reliability study, 305 individuals responded to
VIGITEL interviews, which were repeated with intervals of 7 - 15 days, in Belo
Horizonte, 2013. The evaluated indicators included "sufficiently active on
leisure time," "active in transportation," "inactive in four domains of physical
activity (leisure, work, transportation, and housework)," and "watching TV for
long periods." Kappa coefficient (k) was used to measure agreement between both
interviews. For concurrent validity assessment, the same subjects also responded
to the Global Physical Activity Questionnaire (GPAQ), used as reference method
for comparison of VIGITEL indicators. Comparison was assessed by measures of
sensitivity, specificity, positive (PPV), and negative predictive values (NPV).
Results:: Reliability study showed substantial agreement for active individuals
in leisure time (k = 0.70) and inactive individuals (k = 0.64). The agreement of
watching TV for long periods was moderate (k = 0.56) and the activeness in
transportation showed fair agreement (k = 0.35). In comparison to the reference
method, sensitivity ranged from 54.8 to 67.7 in frequency of inactive, active in
leisure time and work. Transportation domain was represented by 11.9 of
sensitivity. Specificity ranged from 72.0 to 91.2 among four domains of physical
activity and inactive. Conclusion:: Physical activity questionnaire used by the
surveillance system seems to be reliable in all domains, except in transportation
questions. VIGITEL was considered comparable to GPAQ in most aspects of physical
activity evaluation.
PMID- 28513802
TI - Prevalence and factors associated with self-reported disability: a comparison
between genders.
AB - Objective:: To estimate the prevalence of disability and its association with
sociodemographic and health characteristics stratified by sex. Methods:: This is
a cross-sectional study with a probabilistic sample including 4,048 residents
aged >= 18 years in two health districts of Belo Horizonte (MG), Brazil, during
the period from 2008 to 2009. The outcome variable "disability" was established
based on self-reported problems in body functions or structures. Sociodemographic
characteristics ("sex," "age," "skin color," "marital status," "years of
schooling," and "family income") and health ("reported morbidity," "health self
assessment," "quality of life," and "life satisfaction") were the explanatory
variables. We applied the multivariate decision tree analysis by using the Chi
square Automatic Interaction Detector algorithm. Results:: The overall prevalence
of disability corresponded to 10.4% and it was higher in females (11.9%;
confidence interval - 95%CI 10.2 - 13.6) than in males (8.7%; 95%CI 6.8 - 10.5).
In the multivariate analysis, "age" and "morbidity" in females, and "low
educational level" and "poor health self-assessment" in males were the variables
that best discriminated disability. Disability self-reporting was more frequent
among women of working age (40 to 59 years-old) and with lower incomes, as well
as in men with lower educational levels and incomes. With regard to health
conditions, the highest disability percentages were seen among subjects of both
genders that reported three or more diseases and worsened perception of health.
Conclusion:: Results reinforce the need for a distinct approach, since women of
working age and men with lower educational level are more vulnerable to the
occurrence of disability.
PMID- 28513803
TI - Primary Health Care and tuberculosis: services evaluation.
AB - Introduction:: In order to control tuberculosis, the Brazilian Ministry of Health
recommends the decentralization of control actions directed to the Primary Health
Care, and there are few studies on the performance of the Tuberculosis Control
Program in decentralized contexts. Objective:: To evaluate the performance of
Primary Health Care services in tuberculosis treatment. Methods:: This is an
evaluative study with cross-sectional approach conducted in 2011. Two hundred and
thirty-nine health professionals from Primary Health Care units were interviewed
using a structured instrument based on the evaluation reference of the health
services quality (structure - process - results). The performance of these
services was analyzed applying techniques of descriptive statistics, validation,
and construction of indicators and by determining the reduced variable "Z".
Results:: The indicators "participation of professionals in tuberculosis
patients' care" (structure) and "reference and counterreference" (process) had
the best evaluations, whereas "professional training" (structure) and "external
actions for tuberculosis control" (process) had the worst results. Conclusion::
The decentralization of tuberculosis control actions has been taking place in a
vertical manner in Primary Health Care. The challenge of controlling tuberculosis
involves overcoming constraints related to the engagement, training, and turnover
rates among health professionals, which is a coordination between services and
monitoring of control actions in Primary Health Care.
PMID- 28513804
TI - The Brazilian Oral Health Survey (SBBrasil 2010) workflow from the coordinators'
perspective.
AB - Introduction:: Although the workflow of population health surveys may interfere
with the quality of the information produced, this aspect has not been
investigated in the context of oral health. Objective:: To identify the
perception of the Brazilian Oral Health Survey (SBBrasil 2010 Project)
coordinators regarding the survey's workflow. Methods:: Data was collected using
an electronic questionnaire sent to the coordinators after the national survey
was completed. The variables investigated were grouped into themes spanning the
various stages of the survey. Results:: The response rate was of 75.6% (n = 161).
The majority of respondents worked as municipal coordinators in the survey
(82.6%), were females (68%), worked as civil servants in the public health system
(65.2%), and occupied managerial positions (75.8%). The reported positive aspects
of the survey were: planning, training and calibration workshops; the logistic
support provided by both the health system and the survey's coordination team;
the positive relationship between staff members, as well as the survey's
acceptance by respondents and health professionals. The financial assistance
offered for transportation during the survey and issues related to the grants
received by coordinators were seen as negative aspects to be overcome. Most of
the respondents reported that the research experience was useful in qualifying
staff services and showed interest in participating in future oral health
surveys. Conclusion:: The coordinators' perception regarding their workflow in
the SBBrasil 2010 Project was mainly positive. The results may contribute to the
improvement of future oral health surveys.
PMID- 28513805
TI - Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative
Colitis. Part 2: Current Management.
PMID- 28513806
TI - Increased activity of vascular adenosine deaminase in atherosclerosis and
therapeutic potential of its inhibition.
AB - Aims: Extracellular nucleotides and adenosine that are formed or degraded by
membrane-bound ecto-enzymes could affect atherosclerosis by regulating the
inflammation and thrombosis. This study aimed to evaluate a relation between ecto
enzymes that convert extracellular adenosine triphosphate to adenine dinucleotide
phosphate, adenosine monophosphate, adenosine, and inosine on the surface of the
vessel wall with the severity or progression of experimental and clinical
atherosclerosis. Furthermore, we tested whether the inhibition of adenosine
deaminase will block the development of experimental atherosclerosis. Methods and
results: Vascular activities of ecto-nucleoside triphosphate diphosphohydrolase
1, ecto-5'-nucleotidase, and ecto-adenosine deaminase (eADA) were measured in
aortas of apolipoprotein E-/- low density lipoprotein receptor (ApoE-/-LDLR-/-)
and wild-type mice as well as in human aortas. Plaques were analysed in the
entire aorta, aortic root, and brachiocephalic artery by Oil-Red O and Orcein
Martius Scarlet Blue staining and vascular accumulation of macrophages. The
cellular location of ecto-enzymes was analysed by immunofluorescence. The effect
of eADA inhibition on atherosclerosis progression was studied by a 2-month
deoxycoformycin treatment of ApoE-/-LDLR-/- mice. The vascular eADA activity
prominently increased in ApoE-/-LDLR-/- mice when compared with wild type already
at the age of 1 month and progressed along atherosclerosis development, reaching
a 10-fold difference at 10 months. The activity of eADA correlated with
atherosclerotic changes in human aortas. High abundance of eADA in
atherosclerotic vessels originated from activated endothelial cells and
macrophages. There were no changes in ecto-nucleoside triphosphate
diphosphohydrolase 1 activity, whereas ecto-5'-nucleotidase was moderately
decreased in ApoE-/-LDLR-/- mice. Deoxycoformycin treatment attenuated plaque
development in aortic root and brachiocephalic artery of ApoE-/-LDLR-/- mice,
suppressed vascular inflammation and improved endothelial function. Conclusions:
This study highlights the importance of extracellular nucleotides and adenosine
metabolism in the atherosclerotic vessel in both experimental and clinical
setting. The increased eADA activity marks an early stage of atherosclerosis,
contributes to its progression and could represent a novel target for therapy.
PMID- 28513807
TI - The nuclear pore protein Nup153 associates with chromatin and regulates cardiac
gene expression in dystrophic mdx hearts.
AB - Aims: Beyond the control of nuclear-cytoplasmic trafficking nucleoporins regulate
gene expression and are involved in cardiac diseases. Notably, a number of
cardiovascular disorders have been linked to alterations in epigenetic
mechanisms. Here we aimed to determine the contribution of Nup153 to the
epigenetic alterations occurring in cardiomyopathy of dystrophin-deficient mdx
mice (C57BL/10ScSn-Dmd mdx /J). Methods and results: Nup153 was lysine-acetylated
and its expression was significantly increased at protein level in mdx hearts
compared with controls. Accordingly, lysine acetyl transferase (KAT) activity
associated with Nup153 was higher in mdx hearts paralleling increased binding
with the lysine acetylases P300/CBP-associated factor (PCAF) and p300.
Interestingly, Nup153 silencing in mdx organotypic heart tissue slices caused a
reduction in PCAF- and p300-specific activities. Remarkably, the level of nitric
oxide (NO), which is reduced in mdx mice, was important for KAT-dependent
regulation of Nup153. In fact, treatment of mdx heart tissue with an NO donor or
the KAT inhibitor anacardic acid normalized Nup153 protein expression. Nup153 was
recruited to chromatin and regulated the transcription of genes involved in
cardiac remodelling, including the actin-binding protein nexilin. Accordingly,
nexilin protein expression was abrogated by Nup153 silencing in mdx organotypic
cultures. Electrophysiological and molecular experiments revealed that Nup153
overexpression in normal cardiomyocytes increases Ca v 1.2 calcium channel
expression and function. Alterations in Nup153 protein expression and
intracellular localization were also found in dystrophic cardiomyocytes derived
from patient-specific induced pluripotent stem cells. Importantly, Nup153 up
regulation and increased acetylation were also found in the heart of Duchenne
muscular dystrophy patients. Conclusions: Our data indicate that Nup153 is an
epigenetic regulator which, upon altered NO signalling, mediates the activation
of genes potentially associated with early dystrophic cardiac remodelling.
PMID- 28513808
TI - Magnetic nanoparticle-enhanced PCR for the detection and identification of
Staphylococcus aureus and Salmonella enteritidis.
AB - This paper evaluated magnetic nanoparticle-enhanced PCR for the detection and
identification of Staphylococcus aureus and Salmonella enteritidis. Two different
types of magnetic nanoparticles designated MPIO (iron concentration 2.5 mg/ml,
size 1 um) and NP (iron concentration 8.7 mg/ml, size 60 nm), both conjugated
with S. aureus or S. enteritidis antibodies were evaluated as an enrichment
procedure for PCR-detection of the pathogens in Trypticase Soy Broth, milk, blood
and meat broth. Bacterial suspensions (1.5x108 cfu/ml) were prepared and serial
diluted 10-1. The MPIO and NP nanoparticles were added, followed by incubation
for 1 hour at room temperature, magnetic separation of the pellet, DNA extraction
and PCR, targeting the femA and invA sequences. The nanoparticle-free and the NP
supplemented dilutions were positive down to the 1.5x102 cfu/ml concentration for
both bacteria. The MPIO-supplemented dilutions were positive down to approx.
2x100 cfu/ml concentration, respectively. Bacteria-free TSB was negative by PCR.
MPIO nanoparticles (size 1 um) enhanced the detection of S. aureus and S.
enteritidis by PCR, whilst NP nanoparticles (size 60 nm) did not, thus indicating
that the size of the magnetic nanoparticles play a significant role in the
enrichment procedure.
PMID- 28513809
TI - Oral gentamicin therapy for Carbapenem-resistant Klebsiella pneumoniae gut
colonization in hematologic patients: a single center experience.
AB - The mortality for carbapenem-resistant Klebsiella pneumoniae (KPC-Kp) infection
ranges from 18 to 48% depending on the type of therapy. Mortality rates in
hematologic patients are even higher, up to 85%. Gut decontamination with oral
gentamicin might be an option to avoid a subsequent KPC-Kp infection in colonized
patients. We treated 14 hematologic patients with oral gentamicin, 80 mg four
times daily, for 7 to 25 days in order to eradicate KPC-Kp from the gut, starting
oral gentamicin therapy when possible after the discontinuation of systemic
antibiotic therapy. The overall decontamination rate in the entire study
population was 71% (10/14). Out of the 4 patients who did not respond to oral
gentamicin therapy, 1 KPC-Kp strain was gentamicin resistant and 4 patients
received concomitant systemic antibiotic therapy (CSAT). One of these patients
died from KPC-Kp sepsis. The decontamination rate was 90% (9/10) in patients
receiving oral gentamicin only, versus 25% (1/4) in those also treated with CSAT.
No new gentamicin-resistant KPC-Kp strain was isolated during oral gentamicin
therapy Oral gentamicin might be useful for gut decontamination and prevention of
KPC-Kp infection. This option should be considered in patients colonized by a
gentamicin-susceptible KPC-Kp strain and not receiving CSAT.
PMID- 28513810
TI - Epstein-Barr virus encephalitis in solid organ transplantation.
AB - Epstein-Barr virus (EBV) is typically associated with post transplant
lymphoproliferative disease (PTLD) after solid organ and stem cell
transplantation. However, it is rarely associated with neurological
complications. We report a case of severe encephalitis complicating primary EBV
infection six months post renal transplantation, and review the literature on EBV
encephalitis in solid organ transplantation in adults. A 55-year-old male
presented 6 months post cadaveric renal transplant with headache, fever and
confusion. Neuroimaging was unremarkable, but an electroencephalogram was
consistent with diffuse encephalopathy. EBV DNA was detected in both
cerebrospinal fluid (13,177 copies/ml), and plasma (14,166 copies/ml). Management
included reduction of immunosuppression, intravenous ganciclovir and intravenous
immunoglobulin, and resulted in a reduction in EBV viral load in both plasma and
cerebrospinal fluid. The patient made a full recovery with no long-term
neurological deficits and preservation of the graft. This case highlights the
importance of knowing donor and recipient EBV serostatus at time of transplant,
and closely monitoring EBV DNA when there is a mismatch. Ganciclovir or
valganciclovir prophylaxis has also been shown to reduce the incidence of primary
EBV infection in renal transplantation in these recipients. Treatment options for
EBV infection post-transplant include reduction of immunosuppression, antiviral
therapy, IVIg, and monoclonal antibody therapy directed toward infected B
lymphocytes.
PMID- 28513811
TI - An initially unidentified case of urinary tract infection due to Aerococcus
urinae.
AB - Aerococcus urinae is a microorganism responsible for urinary tract and blood
stream infections which are rarely reported in clinical practice. However, it has
been proposed that the infrequency of such reports may be partially due to
difficulties related to pathogen identification. We present here a case of an
elderly male patient with urinary tract infection where A. urinae was initially
not identified by a private microbiology laboratory. Our report highlights the
need to consider A. urinae as a causative agent of urinary tract infections
because if not identified and properly treated it may lead to endocarditis or
septicemia.
PMID- 28513812
TI - Common dermatophytes and in vitro anti-fungal susceptibility testing in patients
attending the Dermatological Clinic at the Hospital for Tropical Medicine,
Bangkok.
AB - Dermatophytes comprising the genera Trichophyton, Microsporum, and Epidermophyton
are important causes of superficial mycoses. The number of infected patients and
the distribution of species of these organisms in our hospital were unknown. We
therefore aimed to investigate the clinical pattern of dermatophyte infections
and to identify the species of these dermatophytes at the Dermatological Clinic
of the Hospital for Tropical Medicine, Faculty of Tropical Medicine, Mahidol
University, Bangkok in a 1-year period. Twenty-six patients who had typical
dermatophytosis lesions were recruited (27 specimens); 17 were female (65.38%)
and 9 (34.62%) were male. The age range of the patients was 16-92 years. In
total, nine dermatophyte isolates were identified by macroscopic and microscopic
morphological characteristics. We found Microsporum canis (four isolates),
Trichophyton mentagrophytes complex (one), Trichophyton rubrum (two),
Trichophyton verrucosum (one), and Trichophyton tonsurans (one). The in vitro
susceptibility profiles of seven antifungal agents against the nine dermatophytes
were as follows (minimum inhibitory concentration ranges in MUg/ml): The results
were as follows (MIC ranges in MUg/ml): ciclopirox, <=0.06-0.5, griseofulvin
<=0.06-0.5, itraconazole <=0.002-0.06, posaconazole <=0.015-0.03, voriconazole
<=0.02->=1, fluconazole <=0.08-8, and terbinafine <=0.01-0.125. This study
represents the current state of dermatophyte infections in a metropolitan area of
Bangkok, Thailand.
PMID- 28513814
TI - Zika virus isolation from semen.
AB - Zika virus (ZIKV) can be sexually transmitted and replicative particles were
first detected in a semen sample from a patient during the 2013-14 French
Polynesia outbreak. Here we describe the virus isolation from semen of a patient
returning to Italy from Brazil.
PMID- 28513813
TI - Hepatitis B virus reactivation after effective sofosbuvir and ribavirin treatment
in a patient with occult hepatitis B virus infection.
AB - Reactivation of the hepatitis B virus (HBV) has been reported in patients with
occult infection (OBI), i.e. HBV surface antigen (HBsAg) negative, HBV core
antibody (anti-HBc) positive +/- antibodies against HBsAg (anti-HBs) and
detectable HBV DNA in serum or liver, receiving immunosuppressive or cytotoxic
therapies. Recently, concerns have been raised regarding the risk of HBV
reactivation in OBI patients treated with direct acting antiviral agents (DAAs)
for chronic hepatitis C (CHC). Here we describe a case of HBV reactivation in a
72-year-old woman with OBI as a possible consequence of effective treatment with
sofosbuvir (SOF) and ribavirin (Rbv) for genotype 2a/2c CHC.
PMID- 28513815
TI - Epidemiology of paediatric meningitis in central Cote d'Ivoire after the
implementation of Haemophilus influenzae type b vaccination.
AB - Infectious meningitis accounts for enormous morbidity worldwide, but there is a
paucity of data on its regional epidemiology in resource-constrained settings of
sub-Saharan Africa. Here, we present a study on the aetiology of paediatric
meningitis in central Cote d'Ivoire. Between June 2012 and December 2013, all
cerebrospinal fluid (CSF) samples drawn at the University Teaching Hospital
Bouake were examined for the presence of bacterial and fungal pathogens. A
causative agent was detected in 31 out of 833 CSF specimens (3.7%), with the most
prevalent pathogens being Streptococcus pneumoniae (n=15) and Neisseria
meningitidis (n=5). With the exception of neonates, these two bacteria were the
most common agents in all age groups. Of note, only a single case of Haemophilus
influenzae meningitis was detected. Hence, this study reports a considerable
shift in the epidemiology of paediatric meningitis in central Cote d'Ivoire.
Following the implementation of a nation-wide childhood vaccination programme
against H. influenzae type b, this pathogen was much less frequently reported
than in previous studies. The integration of specific vaccines against S.
pneumoniae and N. meningitidis into the childhood vaccination programme in
Coted'Ivoire holds promise to further reduce the burden due to infectious
meningitis.
PMID- 28513817
TI - Loss of permanent employment and its association with suicidal ideation: a cohort
study in South Korea.
AB - Objective Precarious employment is associated with worse mental health, but it is
unclear whether changes in employment status are related to suicidal behaviors.
This study examined the association between change in employment status and
suicidal ideation among workers in South Korea. Methods To maximize power of the
analysis, we combined data from the ongoing Korean Welfare Panel Study. We
analyzed 3793 participants who were permanent workers at baseline (2011-2014) and
who either: (i) maintained permanent employment; (ii) became a full-time
precarious worker; (iii) became a part-time precarious worker; or (iv) became
unemployed in the following year (2012-2015). Suicidal ideation was assessed
annually by asking participants, "Have you ever seriously thought about dying by
suicide in the past year?" Logistic regression was applied to examine
associations between change in employment status and suicidal ideation, adjusting
for potential confounders such as lifetime suicidal ideation and depressive
symptoms at baseline. Results Participants who became part-time precarious
workers were more likely to have suicidal ideation [odd ratio (OR) 2.37, 95%
confidence interval (95% CI) 1.07-5.25, P=0.033] compared to those who remained
permanent workers. In analysis restricted to workers who never previously thought
about dying by suicide, suicidal ideation was more common among those who became
either full-time (OR 2.33, 95% CI 1.09-4.99, P=0.029) or part-time (OR 3.94, 95%
CI 1.46-10.64, P=0.007) precarious workers. Conclusions Our findings suggest that
change in employment status from permanent to precarious employment may increase
suicidal ideation among workers in South Korea.
PMID- 28513818
TI - The risk of melanoma associated with ambient summer ultraviolet radiation.
AB - BACKGROUND: Depletion of the ozone layer has meant that ambient ultraviolet
radiation (UVR) has increased in recent decades. At the same time, the incidence
of skin cancers, including melanoma, has risen. The relatively few large-scale
studies that linked ambient UVR to melanoma found a trend toward rising incidence
closer to the equator, where UVR estimates are highest. Similar research has not
been conducted in Canada, where ambient UVR is generally lower than in countries
further south. DATA AND METHODS: Modelled UVR data for the months of June through
August during the 1980-to-1990 period were spatially linked in Geographic
Information Systems to 2.4 million white members of the 1991 Canadian Census
Health and Environment Cohort and tracked for melanoma diagnosis over an 18-year
period (1992 to 2009). Standard Cox proportional hazards models were used to
estimate melanoma risk associated with increases of ambient summer UVR, assigned
by residence at baseline. Models were adjusted for age, sex and socioeconomic
(SES) characteristics. Separate analyses by body site of melanoma were conducted.
Effect modification of the association between ambient UVR and melanoma by sex,
age, outdoor occupation and selected SES characteristics was evaluated. RESULTS:
Differences of one standard deviation (446 J/m2, or 7% of the mean) in average
ambient summer UVR were associated with an increased hazard ratio (HR) for
melanoma of 1.22 (95% CI: 1.19 to 1.25) when adjusting for sex, age and SES
characteristics. The HR for melanoma in relative UVR (per 1 standard deviation)
was larger for men (HR = 1.26; 95% CI: 1.21 to 1.30) than for women (HR = 1.17;
95% CI: 1.13 to 1.22). INTERPRETATION: Ambient summer UVR is associated with a
greater risk of melanoma among the white population, even in a country where most
people live within a narrow latitudinal belt. A stronger association between
melanoma and ambient UVR was evident among men and among people of lower SES.
PMID- 28513819
TI - Sun exposure, sun protection and sunburn among Canadian adults.
AB - BACKGROUND: Ultraviolet radiation (UVR) exposure and a history of sunburn are
important risk factors for skin cancer. Sunburn is more common among men, younger
age groups, and people in higher income households. Sun protection measures also
vary by sex, age, and socioeconomic characteristics. Associations between ambient
UVR and sunburn and sun safety measures have not been quantified. DATA AND
METHODS: A total of 53,130 respondents aged 18 or older answered a Canadian
Community Health Survey (CCHS) module on sun safety, which was administered in
six provinces from 2005 to 2014. The module contained questions about sunburn,
time in the sun, and sun protection. These respondents were linked to an ambient
erythemal UVR dataset representing the June-to-August mean. Descriptive
statistics and logistic regression were used to examine associations between
population characteristics, sunburn, sun safety, time in the sun, and ambient
UVR. RESULTS: Sunburn was reported by 33% of respondents and was more common
among men, younger age groups, people who were not members of visible minorities,
residents of higher income households, and individuals who were employed. On a
typical summer day, a larger percentage of women than men sought shade and wore
sunscreen, whereas a larger percentage of men wore a hat or long pants. As
ambient summer UVR increased, women were more likely to apply sunscreen to their
face, seek shade, or wear a hat (OR~1.02 to 1.09 per increase of 187 J/m2 of
erythemally-weighted UVR, or 5.4% of the mean); these associations were not
observed among men. INTERPRETATION: Findings related to sunburn and sun
protection were similar to those of previous studies. The association between
ambient UVR and women's precautionary measures suggests that information about
UVR may influence their decision to protect their skin.
PMID- 28513816
TI - Italian guidelines for the use of antiretroviral agents and the diagnostic
clinical management of HIV-1 infected persons. Update 2016.
AB - The Italian Society of Infectious and Tropical Diseases (SIMIT) of the Technical
Health Committee, Ministry of Health (Sections L and M) of Italy have supported
recommendations for the Italian guidelines for the use of antiretroviral agents
and the diagnostic-clinical management of HIV-1 infected persons. This
publication summarizes the latest updates to the 2016 version of the Italian
Guidelines for the management of HIV-1 infected patients and the use of
antiretroviral drugs. In particular, new recommendations were released concerning
the following topics: estimate of the HIV continuum of care in Italy, optimal
timing and preferred drug combinations for starting antiretroviral therapy,
treatment optimization, and pre-exposure prophilaxis (PrEP). For a complete
review of clinical and therapeutic relevant topics we refer the reader to the
extended version of the Guidelines.
PMID- 28513820
TI - Intra-abdominal hypertension and abdominal compartment syndrome in acute
pancreatitis, hepato-pancreato-biliary operations and liver transplantation.
AB - Intra-abdominal hypertension, even preceding the onset of abdominal compartment
syndrome, is still recognized as an adverse prognostic factor. Unfortunately,
most of the current supporting evidence within the critical care environment
remains observational in nature. In acute pancreatitis, an active role for intra
abdominal hypertension early in the disease process follows a strong intuitive
basis, and it is corroborated by preliminary evidence from animal models.
Additional studies are needed to better characterize the optimal fluid
resuscitation strategy, as well as the importance of intra-abdominal hypertension
as an early therapeutic target. All critically ill patients with acute
pancreatitis should be considered for routine intra-abdominal pressure
monitoring. The prevalence and clinical relevance of intra-abdominal hypertension
after elective major abdominal operations are underestimated in the literature.
Hepato-pancreato-biliary surgery and liver transplantation represent high-risk
surgical subspecialties, and routine intra-abdominal hypertension risk assessment
to indicate postoperative intra-abdominal pressure monitoring can be recommended.
Conservative management of intra-abdominal hypertension should be promptly
initiated upon diagnosis. Although abdominal catheter drainage and decompressive
laparotomy may be required in refractory cases based on expert clinical judgment,
precise indications and timing are still unclear. Implementation of institutional
protocols based on the Abdominal Compartment Society reference standards is
crucial to optimize both clinical management and research in this evolving area.
PMID- 28513822
TI - Abdominal pressure and gastrointestinal function: an inseparable couple?
AB - Evaluating the degree of organ dysfunction is a cornerstone in distinguishing
patients with critical illness from those without. However, evaluation of the
gastrointestinal function in critically ill patients is not unified, and is still
largely based on subjective clinical evaluation. Although intra-abdominal
pressure has been proposed as a parameter to facilitate monitoring of abdominal
compartment in critical illness, the interactions between intra-abdominal
pressure and gastrointestinal function are poorly clarified. The aim of this
current review is to describe interactions and associations between
gastrointestinal dysfunction and intra-abdominal pressure from a
pathophysiological and clinical point of view.
PMID- 28513821
TI - Platelets in sepsis - are there any new aspects?
AB - Platelets display a number of properties besides the crucial function of
repairing a damaged vascular endothelium and stopping bleeding. Platelets
constitutively express molecules that are classically acknowledged to function in
primary haemostasis. Platelets specialize in pro-inflammatory activities, and can
secrete a large number of molecules, many of which display biological response
modifier functions. Recently, platelets expressing receptors for infectious and
possibly noninfectious danger signals were shown to be involved in
pathophysiological reactions including an immune-inflammatory response. In
sepsis, platelets play a key role in immunothrombosis, participate in the
formation of NETs (neutrophil extracellular trap) resulting in the trapping and
killing of pathogens and are one of the main factors influencing mortality.
PMID- 28513824
TI - How we treat germ cell cancers.
PMID- 28513823
TI - Adjuvant radiotherapy improves overall survival in patients with resected gastric
adenocarcinoma: A National Cancer Data Base analysis.
AB - BACKGROUND: For patients with resectable gastric adenocarcinoma, perioperative
chemotherapy and adjuvant chemoradiotherapy (CRT) are considered standard
options. In the current study, the authors used the National Cancer Data Base to
compare overall survival (OS) between these regimens. METHODS: Patients who
underwent gastrectomy for nonmetastatic gastric adenocarcinoma from 2004 through
2012 were divided into those treated with perioperative chemotherapy without RT
versus those treated with adjuvant CRT. Survival was estimated and compared using
univariate and multivariate models adjusted for patient and tumor
characteristics, surgical margin status, and the number of lymph nodes examined.
Subset analyses were performed for factors chosen a priori, and potential
interactions between treatment and covariates were assessed. RESULTS: A total of
3656 eligible patients were identified, 52% of whom underwent perioperative
chemotherapy and 48% of whom received postoperative CRT. The median follow-up was
47 months, and the median age of the patients was 62 years. Analysis of the
entire cohort demonstrated improved OS with adjuvant RT on both univariate
(median of 51 months vs 42 months; P = .013) and multivariate (hazard ratio,
0.874; 95% confidence interval, 0.790-0.967 [P = .009]) analyses. Propensity
score-matched analysis also demonstrated improved OS with adjuvant RT (median of
49 months vs 39 months; P = .033). On subset analysis, a significant interaction
was observed between the survival impact of adjuvant RT and surgical margins,
with a greater benefit of RT noted among patients with surgical margin-positive
disease (hazard ratio with RT: 0.650 vs 0.952; P for interaction <.001).
CONCLUSIONS: In this National Cancer Data Base analysis, the use of adjuvant RT
in addition to chemotherapy was associated with a significant OS advantage for
patients with resected gastric cancer. The survival advantage observed with
adjuvant CRT was most pronounced among patients with positive surgical margins.
Cancer 2017;123:3402-9. (c) 2017 American Cancer Society.
PMID- 28513826
TI - Noncontingent reinforcement without extinction plus differential reinforcement of
alternative behavior during treatment of problem behavior.
AB - The effects of noncontingent reinforcement (NCR) without extinction during
treatment of problem behavior maintained by social positive reinforcement were
evaluated for five individuals diagnosed with autism spectrum disorder. A
continuous NCR schedule was gradually thinned to a fixed-time 5-min schedule. If
problem behavior increased during NCR schedule thinning, a continuous NCR
schedule was reinstated and NCR schedule thinning was repeated with differential
reinforcement of alternative behavior (DRA) included. Results showed an immediate
decrease in all participants' problem behavior during continuous NCR, and problem
behavior maintained at low levels during NCR schedule thinning for three
participants. Problem behavior increased and maintained at higher rates during
NCR schedule thinning for two other participants; however, the addition of DRA to
the intervention resulted in decreased problem behavior and increased mands.
PMID- 28513825
TI - Loss of TET1 facilitates DLD1 colon cancer cell migration via H3K27me3-mediated
down-regulation of E-cadherin.
AB - Epigenetic modifications such as histone modifications and cytosine
hydroxymethylation are linked to tumorigenesis. Loss of 5-hydroxymethylcytosine
(5 hmC) by ten-eleven translocation 1 (TET1) down-regulation facilitates tumor
initiation and development. However, the mechanisms by which loss of TET1
knockdown promotes malignancy development remains unclear. Here, we report that
TET1 knockdown induced epithelial-mesenchymal transition (EMT) and increased
cancer cell growth, migration, and invasion in DLD1 cells. Loss of TET1 increased
EZH2 expression and reduced UTX-1 expression, thus increasing histone H3K27 tri
methylation causing repression of the target gene E-cadherin. Ectopic expression
of the H3K27 demethylase UTX-1 or EZH2 depletion both impeded EZH2 binding caused
a loss of H3K27 methylation at epithelial gene E-cadherin promoter, thereby
suppressing EMT and tumor invasion in shTET1 cells. Conversely, UTX-1 depletion
and ectopic expression of EZH2 enhanced EMT and tumor metastasis in DLD1 cells.
These findings provide insight into the regulation of TET1 and E-cadherin and
identify EZH2 as a critical mediator of E-cadherin repression and tumor
progression.
PMID- 28513827
TI - Using the dual-criteria methods to supplement visual inspection: An analysis of
nonsimulated data.
AB - The purpose of our study was to examine the probability of observing false
positives in nonsimulated data using the dual-criteria methods. We extracted data
from published studies to produce a series of 16,927 datasets and then assessed
the proportion of false positives for various phase lengths. Our results indicate
that collecting at least three data points in the first phase (Phase A) and at
least five data points in the second phase (Phase B) is generally sufficient to
produce acceptable levels of false positives.
PMID- 28513829
TI - An analysis of procedures that affect response variability.
AB - Response variability is sensitive to antecedent and consequent manipulations.
Researchers have investigated inducement, direct production through
reinforcement, and stimulus control of response variability. Recently,
researchers have shown that lag reinforcement schedules reliably increase
variability but may also produce higher-order stereotypy. There has been limited
investigation of appropriate variability levels and alternation between
repetition and variation. In a three-part study, we evaluated levels of
variability across a group of children, the effects of various procedures on
producing response variability and novelty, and the use of schedule-correlated
stimuli for producing rapid alternation between repetition and variation. In
Study 1, there was a nearly bimodal distribution of children emitting either low
or high variability. In Study 2, for most children, fixed lag 4 and variable lag
4 schedules produced the highest levels of variability and novelty. In Study 3,
responding was brought under control of schedule-correlated stimuli, allowing for
rapid alternation between repetition and variation.
PMID- 28513828
TI - Outcome of autologous hematopoietic stem cell transplantation in refractory
multiple myeloma.
AB - BACKGROUND: Despite the introduction of effective, novel agents, the outcome of
patients with refractory multiple myeloma remains poor, particularly those who
are refractory to both proteasome inhibitors (PIs) and immunomodulatory agents
(IMiDs). Limited data are available on the role of autologous hematopoietic stem
cell transplantation in this population. METHODS: Patients with refractory
myeloma who underwent first autologous hematopoietic stem cell transplantation
(auto-HCT) between March 2000 and October 2015 were retrospectively analyzed.
Those who had primary refractory disease and those with relapsed and refractory
disease were included. Disease that was refractory to at least 1 PI and at least
1 IMiD was classified as double-refractory multiple myeloma (DR-MM). RESULTS: In
total, 233 patients were identified, including 105 (45%) classified with DR-MM
and 128 (55%) classified with nondouble-refractory myeloma (NDR-MM). At a median
follow-up of 42 months for surviving patients, at least a partial response was
observed in 188 patients (81%; 83 patients in the DR-MM group [79%] and 105
patients in the NDR-MM [82%]; P = .77). A near complete response or better was
observed in 52 patients (22%; 25 patients in the DR-MM group [24%] and 27
patients in the NDR-MM group [21%]; P = .77). The median progression-free
survival was 17.6 months (14.4 months in the DR-MM group and 18.2 months in the
NDR-MM group), and the 2-year progression-free survival rate was 38% (35% in the
DR-MM group and 40% in the NDR-MM group; P = .40). The median overall survival
was 48 months (38.9 months in the DR-MM group and 56.6 months in the NDR-MM
group), and the 2-year overall survival rate was 74% (71% in the DR-MM group and
76% in the NDR-MM group; P = .27). CONCLUSIONS: The current findings indicate
that auto-HCT is an effective and safe therapy in patients with refractory
multiple myeloma, including those who are refractory to IMiDs and PIs. Cancer
2017;123:3568-75. (c) 2017 American Cancer Society.
PMID- 28513831
TI - Avoidance versus use of neuromuscular blocking agents for improving conditions
during tracheal intubation or direct laryngoscopy in adults and adolescents.
AB - BACKGROUND: Tracheal intubation during induction of general anaesthesia is a
vital procedure performed to secure a patient's airway. Several studies have
identified difficult tracheal intubation (DTI) or failed tracheal intubation as
one of the major contributors to anaesthesia-related mortality and morbidity. Use
of neuromuscular blocking agents (NMBA) to facilitate tracheal intubation is a
widely accepted practice. However, because of adverse effects, NMBA may be
undesirable. Cohort studies have indicated that avoiding NMBA is an independent
risk factor for difficult and failed tracheal intubation. However, no systematic
review of randomized trials has evaluated conditions for tracheal intubation,
possible adverse effects, and postoperative discomfort. OBJECTIVES: To evaluate
the effects of avoiding neuromuscular blocking agents (NMBA) versus using NMBA on
difficult tracheal intubation (DTI) for adults and adolescents allocated to
tracheal intubation with direct laryngoscopy. To look at various outcomes,
conduct subgroup and sensitivity analyses, examine the role of bias, and apply
trial sequential analysis (TSA) to examine the level of available evidence for
this intervention. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, BIOSIS,
International Web of Science, LILACS, advanced Google, CINAHL, and the following
trial registries: Current Controlled Trials; ClinicalTrials.gov; and
www.centerwatch.com, up to January 2017. We checked the reference lists of
included trials and reviews to look for unidentified trials. SELECTION CRITERIA:
We included randomized controlled trials (RCTs) that compared the effects of
avoiding versus using NMBA in participants 14 years of age or older. DATA
COLLECTION AND ANALYSIS: Two review authors extracted data independently. We
conducted random-effects and fixed-effect meta-analyses and calculated risk
ratios (RRs) and their 95% confidence intervals (CIs). We used published data and
data obtained by contacting trial authors. To minimize the risk of systematic
error, we assessed the risk of bias of included trials. To reduce the risk of
random errors caused by sparse data and repetitive updating of cumulative meta
analyses, we applied TSA. MAIN RESULTS: We identified 34 RCTs with 3565
participants that met our inclusion criteria. All trials reported on conditions
for tracheal intubation; seven trials with 846 participants described 'events of
upper airway discomfort or injury', and 13 trials with 1308 participants reported
on direct laryngoscopy. All trials used a parallel design. We identified 18 dose
finding studies that included more interventions or control groups or both. All
trials except three included only American Society of Anesthesiologists (ASA)
class I and II participants, 25 trials excluded participants with anticipated
DTI, and obesity or overweight was an excluding factor in 13 studies. Eighteen
trials used suxamethonium, and 18 trials used non-depolarizing NMBA.Trials with
an overall low risk of bias reported significantly increased risk of DTI with no
use of NMBA (random-effects model) (RR 13.27, 95% CI 8.19 to 21.49; P < 0.00001;
508 participants; four trials; number needed to treat for an additional harmful
outcome (NNTH) = 1.9, I2 = 0%, D2 = 0%, GRADE = moderate). The TSA-adjusted CI
for the RR was 1.85 to 95.04. Inclusion of all trials resulted in confirmation of
results and of significantly increased risk of DTI when an NMBA was avoided
(random-effects model) (RR 5.00, 95% CI 3.49 to 7.15; P < 0.00001; 3565
participants; 34 trials; NNTH = 6.3, I2 = 70%, D2 = 82%, GRADE = low). Again the
cumulative z-curve crossed the TSA monitoring boundary, demonstrating harmful
effects of avoiding NMBA on the proportion of DTI with minimal risk of random
error. We categorized only one trial reporting on upper airway discomfort or
injury as having overall low risk of bias. Inclusion of all trials revealed
significant risk of upper airway discomfort or injury when an NMBA was avoided
(random-effects model) (RR 1.37, 95% CI 1.09 to 1.74; P = 0.008; 846
participants; seven trials; NNTH = 9.1, I2 = 13%, GRADE = moderate). The TSA
adjusted CI for the RR was 1.00 to 1.85. None of these trials reported mortality.
In terms of our secondary outcome 'difficult laryngoscopy', we categorized only
one trial as having overall low risk of bias. All trials avoiding NMBA were
significantly associated with difficult laryngoscopy (random-effects model) (RR
2.54, 95% CI 1.53 to 4.21; P = 0.0003; 1308 participants; 13 trials; NNTH = 25.6,
I2 = 0%, D2= 0%, GRADE = low); however, TSA showed that only 6% of the
information size required to detect or reject a 20% relative risk reduction (RRR)
was accrued, and the trial sequential monitoring boundary was not crossed.
AUTHORS' CONCLUSIONS: This review supports that use of an NMBA may create the
best conditions for tracheal intubation and may reduce the risk of upper airway
discomfort or injury following tracheal intubation. Study results were
characterized by indirectness, heterogeneity, and high or uncertain risk of bias
concerning our primary outcome describing difficult tracheal intubation.
Therefore, we categorized the GRADE classification of quality of evidence as
moderate to low. In light of defined outcomes of individual included trials, our
primary outcomes may not reflect a situation that many clinicians consider to be
an actual difficult tracheal intubation by which the patient's life or health may
be threatened.
PMID- 28513830
TI - Association between mutations of critical pathway genes and survival outcomes
according to the tumor location in colorectal cancer.
AB - BACKGROUND: Colorectal cancer (CRC) develops through the alteration of several
critical pathways. This study was aimed at evaluating the influence of critical
pathways on survival outcomes for patients with CRC. METHODS: Targeted next
generation sequencing of 40 genes included in the 5 critical pathways of CRC
(WNT, P53, RTK-RAS, phosphatidylinositol-4,5-bisphosphate 3-kinase [PI3K], and
transforming growth factor beta [TGF-beta]) was performed for 516 patients with
stage III or high-risk stage II CRC treated with surgery followed by adjuvant
fluoropyrimidine and oxaliplatin chemotherapy. The associations between critical
pathway mutations and relapse-free survival (RFS) and overall survival were
analyzed. The associations were further analyzed according to the tumor location.
RESULTS: The mutation rates for the WNT, P53, RTK-RAS, PI3K, and TGF-beta
pathways were 84.5%, 69.0%, 60.7%, 30.0%, and 28.9%, respectively. A mutation in
the PI3K pathway was associated with longer RFS (adjusted hazard ratio [HR],
0.59; 95% confidence interval [CI], 0.36-0.99), whereas a mutation in the RTK-RAS
pathway was associated with shorter RFS (adjusted HR, 1.60; 95% CI, 1.01-2.52).
Proximal tumors showed a higher mutation rate than distal tumors, and the
mutation profile was different according to the tumor location. The mutation
rates of Kirsten rat sarcoma viral oncogene homolog (KRAS), phosphatidylinositol
4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and B-Raf proto
oncogene serine/threonine kinase (BRAF) were higher in proximal tumors, and the
mutation rates of adenomatous polyposis coli (APC), tumor protein 53 (TP53), and
neuroblastoma RAS viral oncogene homolog (NRAS) were higher in distal tumors. The
better RFS with the PI3K pathway mutation was significant only for proximal
tumors, and the worse RFS with the RTK-RAS pathway mutation was significant only
for distal tumors. CONCLUSIONS: A PI3K pathway mutation was associated with
better RFS for CRC patients treated with adjuvant chemotherapy, and an RTK-RAS
pathway mutation was associated with worse RFS. The significance of the
prognostic impact differed according to the tumor location. Cancer 2017;123:3513
23. (c) 2017 American Cancer Society.
PMID- 28513832
TI - Endless forms most hidden: katydids that masquerade as moss.
PMID- 28513833
TI - Potential role and prognostic importance of dishevelled-2 in epithelial ovarian
cancer.
AB - OBJECTIVE: To investigate the role and prognostic importance of Dvl2 in human
epithelial ovarian cancer (EOC). METHODS: A multimethod study was undertaken
including patients with pathologically confirmed non-metastatic EOC who underwent
surgery for maximum tumor resection at a center in China. Dvl2 expression was
assessed by western blot using fresh EOC tissues and normal ovarian tissues
obtained between June 2014 and January 2015. Additionally, retrospective data
were obtained for patients treated between April 2004 and September 2009. Their
tumor specimens were used in immunohistochemistry analysis. Kaplan-Meier survival
plots were constructed to estimate the overall survival by Dvl2 expression, and a
Cox proportional hazards model was used to analyze prognostic factors.
Alterations in Dvl2 expression during the cell cycle were assessed by a
starvation and refeeding assay. RESULTS: Dvl2 expression was higher in EOC
samples than in normal tissues on western blot. Overall, 124 patients were
included in immunohistochemistry analysis, and Dvl2 expression level was
significantly associated with the tumor grade and Ki-67 expression.
Overexpression of Dvl2 was correlated with poor prognosis. The pattern of Dvl2
expression throughout the cell cycle matched that of the cell proliferation
marker cyclin D1. CONCLUSION: Dvl2 could play a part in EOC progression and might
be an independent prognostic factor. Additionally, it might be a prospective
therapeutic target in the treatment of EOC.
PMID- 28513834
TI - The association between complications and quality of life after mastectomy and
breast reconstruction for breast cancer.
AB - BACKGROUND: Medical treatment for breast cancer is associated with substantial
toxicity and patient burden. There is less known about the impact of surgical
complications. Understanding this impact could provide important information for
patients when they are considering surgical options. METHODS: Between 2008 and
2009, the UK National Mastectomy and Breast Reconstruction Audit recorded
surgical complications for a prospective cohort of 17,844 women treated for
breast cancer at 270 hospitals; 6405 of these women were surveyed about their
quality of life 18 months after surgery. Breast appearance, emotional well-being,
and physical well-being were quantified on 0- to 100-point scales. Linear
multiple regression models, controlling for a range of baseline prognostic
factors, were used to compare the scores of patients who had complications with
the scores of those who did not. RESULTS: The overall complication rate was
10.2%. Complications were associated with little or no impairment in women
undergoing mastectomy without reconstruction or with delayed reconstruction. The
association was much larger for flap-related complications suffered during
immediate reconstruction. The breast-appearance scores (adjusted mean difference,
-23.8; 95% confidence interval [CI], -31.0 to -16.6) and emotional well-being
scores (adjusted mean difference, -14.0; 95% CI, -22.0 to -6.0) of these patients
were much lower than those of any other patient group. Implant-related
complications were not associated with a lower quality of life in any surgical
group. CONCLUSIONS: There is a strong case for prospectively collecting flap
complication rates at the surgeon and surgical unit level and for allowing
patients to access these data when they make choices about their breast cancer
surgery. Cancer 2017;123:3460-7. (c) 2017 American Cancer Society.
PMID- 28513835
TI - British Association of Dermatologists guidelines for biologic therapy for
psoriasis 2017.
PMID- 28513839
TI - Improving Specialty Care of Older Adults: Creating Champions, Supporting
Research, Fostering Partnerships.
PMID- 28513838
TI - The emerging role of NPNT in tissue injury repair and bone homeostasis.
AB - Nephronectin (NPNT), a highly conserved extracellular matrix protein, plays an
important role in regulating cell adhesion, differentiation, spreading, and
survival. NPNT protein belongs to the epidermal growth factor (EGF)-like
superfamily and exhibits several common structural determinants; including EGF
like repeat domains, MAM domain (Meprin, A5 Protein, and Receptor Protein
Tyrosine Phosphatase u), RGD motif (Arg-Gly-Asp) and a coiled-coil domain. It
regulates integrins-mediated signaling pathways via the interaction of its RGD
motif with integrin alpha8beta1. Recent studies revealed that NPNT is involved in
kidney development, renal injury repair, atrioventricular canal differentiation,
pulmonary function, and muscle cell niche maintenance. Moreover, NPNT regulates
osteoblast differentiation and mineralization, as well as osteogenic
angiogenesis. Altered expression of NPNT has been linked with the progression of
certain types of cancers, such as spontaneous breast tumor metastasis and
malignant melanoma. Interestingly, NPNT gene expression can be regulated by a
range of external factors such as tumor necrosis factor alpha (TNF-alpha),
transforming growth factor beta (TGF-beta), oncostatin M (OSM), bone morphogenic
protein 2 (BMP2), Wnt3a, Vitamin D3 , and microRNA-378 (miR378). Further
understanding the cellular and molecular mechanisms by which NPNT regulates
tissue homeostasis in an organ-specific manner is critical in exploring NPNT as a
therapeutic target for tissue regeneration and tissue engineering.
PMID- 28513836
TI - Facilitation of mossy fibre-driven spiking in the cerebellar nuclei by the
synchrony of inhibition.
AB - KEY POINTS: Large premotor neurons of the cerebellar nuclei (CbN cells) integrate
synaptic inhibition from Purkinje neurons and synaptic excitation from mossy
fibres to generate cerebellar output. We find that mossy fibre inputs to CbN
cells generate unitary AMPA receptor EPSCs of ~1 nS that decay in ~1 ms and
mildly voltage-dependent NMDA receptor EPSCs of ~0.6 nS that decay in ~7 ms. A
few hundred mossy fibres active at a few tens of spikes s-1 must converge on CbN
cells to generate physiological CbN spike rates (~60 spikes s-1 ) during
convergent inhibition from spontaneously active Purkinje cells. Dynamic clamp
studies in cerebellar slices from weanling mice demonstrate that synaptic
excitation from mossy fibres becomes more effective at increasing the rate of CbN
cell spiking when the coherence (synchrony) of convergent inhibition is
increased. ABSTRACT: Large projection neurons of the cerebellar nuclei (CbN
cells), whose activity generates movement, are inhibited by Purkinje cells and
excited by mossy fibres. The high convergence, firing rates and strength of
Purkinje inputs predict powerful suppression of CbN cell spiking, raising the
question of what activity patterns favour excitation over inhibition. Recording
from CbN cells at near-physiological temperatures in cerebellar slices from
weanling mice, we measured the amplitude, kinetics, voltage dependence and short
term plasticity of mossy fibre-mediated EPSCs. Unitary EPSCs were small and brief
(AMPA receptor, ~1 nS, ~1 ms; NMDA receptor, ~0.6 nS, ~7 ms) and depressed
moderately. Using these experimentally measured parameters, we applied
combinations of excitation and inhibition to CbN cells with dynamic clamp.
Because Purkinje cells can fire coincident simple spikes during cerebellar
behaviours, we varied the proportion (0-20 of 40) and precision (0-4 ms jitter)
of synchrony of inhibitory inputs, along with the rates (0-100 spikes s-1 ) and
number (0-800) of excitatory inputs. Even with inhibition constant, when
inhibitory synchrony was higher, excitation increased CbN cell firing rates more
effectively. Partial inhibitory synchrony also dictated CbN cell spike timing,
even with physiological rates of excitation. These effects were present with >=10
inhibitory inputs active within 2-4 ms of each other. Conversely, spiking was
most effectively suppressed when inhibition was maximally asynchronous. Thus, the
rate and relative timing of Purkinje-mediated inhibition set the rate and timing
of cerebellar output. The results suggest that increased coherence of Purkinje
cell activity can facilitate mossy fibre-driven spiking by CbN cells, in turn
driving movements.
PMID- 28513837
TI - Maternal near miss in low-resource areas.
AB - OBJECTIVE: To describe the Global Network Near-Miss Maternal Mortality System and
its application in seven sites. METHODS: In a population-based study, pregnant
women eligible for enrollment in the Maternal and Newborn Health Registry at
seven sites (Democratic Republic of the Congo; Guatemala; Belagavi and Nagpur,
India; Kenya; Pakistan; and Zambia) between January 2014 and April 2016 were
screened to identify those likely to have a near-miss event. The WHO maternal
near-miss criteria were modified for low-resource settings. The ratio of near
miss events to maternal deaths was calculated. RESULTS: Among 122 707 women
screened, 18 307 (15.0%) had a potential near-miss event, of whom 4866 (26.6%;
4.0% of all women) had a near-miss maternal event. The overall maternal mortality
ratio was 155 per 100 000 live births. The ratio of near-miss events to maternal
deaths was 26 to 1. The most common factors involved in near-miss cases were the
hematologic/coagulation system, infection, and cardiovascular system. CONCLUSION:
By using the Global Network Near-Miss Maternal Mortality System, large numbers of
women were screened for near-miss events, including those delivering at home or a
low-level maternity clinic. The 4.0% incidence of near-miss maternal mortality is
similar to previously reported data. The ratio of 26 near-miss cases to 1
maternal death suggests that near miss might evaluate the impact of interventions
more efficiently than maternal mortality.
PMID- 28513841
TI - Incorporating multiple secondary targets into learning trials for individuals
with autism spectrum disorder.
AB - The current study examined the outcome of presenting multiple secondary targets
in learning trials for individuals with autism spectrum disorder. We compared
conditions in which (a) a secondary target was presented in the antecedent and
consequence of trials, (b) two secondary targets were presented in the
consequence of trials, (c) one secondary target was presented in the consequence
of each trial, and (d) no additional targets were presented trials. The
participants acquired the majority of secondary targets. Presenting one or
multiple secondary targets per trial, regardless of the location of these
secondary targets, increased the efficiency of instruction in comparison to a
condition with no secondary target.
PMID- 28513842
TI - Expanding the Field of Surgical Researchers: The Jahnigen Career Development
Award.
AB - Under a long-standing collaboration with the John A. Hartford Foundation (JAHF),
the Atlantic Philanthropies (AP), and specialty societies in 10 targeted
specialties, the American Geriatrics Society (AGS) has been working to improve
quality of care provided to older adults by surgical and related medical
specialists. To support and nurture future academic leaders, the Geriatrics-for
Specialists Initiative (GSI) established the Dennis W. Jahnigen Career
Development Scholar Award (JCDA) program in 2002, with AP joining JAHF as a core
funder of the awards in 2003. Commencing in 2011, the National Institute on Aging
(NIA) launched the Grants for Early Medical/Surgical Specialists' Transition to
Aging Research (GEMSSTAR) program, using an RO3 mechanism. Recipients of the JCDA
and the GEMSSTAR are provided with 2 years of research support and networking
opportunities with other scholars; 79 JCDA and 26 surgical and related medical
specialty GEMSSTAR scholars have been funded through these award mechanisms, with
AGS, JAHF, and surgical and related medical specialty societies providing
matching support for 20 of the GEMSSTAR scholars for leadership development
programs. One of the primary criteria for judging the overall success of the
program was eventual transition of the award to a federally funded program, which
was achieved when NIA launched the GEMSSTAR program in 2011.
PMID- 28513840
TI - Histomorphology and innate immunity during the progression of osteoarthritis:
Does synovitis affect cartilage degradation?
AB - Osteoarthritis (OA) is a common chronic degenerative disease that affects all
joints. At present, the pathological processes and mechanisms of OA are still
unclear. Innate immunity, a key player in damage to the structure of the joint
and the mechanism by which the host attempts to repair OA, affects all
pathological stages of the disease. In the present study, our aim was to assess
changes in innate immunity during the pathological processes of OA in articular
cartilage (AC) and the synovial membrane (SM), which are the major structures in
joints, and to systematically examine the histological changes in AC and SM in
mild, moderate and severe cases of OA, in order to further speculate about the
manner in which the interactions of AC and SM are facilitated by innate immunity.
Histological methods (including HE and Safranin O-fast green staining),
immunofluorescent double staining, TUNEL stain, and Western blots were used to
assess the morphological changes within AC and SM tissues in healthy and mild,
moderate, or severe OA rats. Our results showed that the damage to AC and SM
within the joints progressively worsened in different degrees during the course
of the disease, and that the innate immune system was closely involved in the AC
and SM during each stage of OA. These findings also confirmed that SM may affect
the pathological changes in AC through the innate immune system, and therefore
affect the progress of OA.
PMID- 28513843
TI - Meeting the Need for Training in Geriatrics: The Geriatrics Education for
Specialty Residents Program.
AB - The imperative created by increasing numbers of aging Americans coupled with
increasing longevity has generated recognition and acceptance within american
medicine that education, from medical school through postgraduate training
through continuing medical education, must include appropriate knowledge and
skills in aging and geriatrics to provide for effective care of older adults.
Such education and training is necessary not only for traditional primary care
providers, but also for specialty physicians, including those in most surgical
specialties and in related fields such as anesthesiology, emergency medicine and
physical medicine and rehabilitation. To fill this demand, the American
Geriatrics Society Geriatrics for Specialist Initiative established the
Geriatrics Education for Specialty Residents Program (GSR). This article reviews
the process by which the GSR created a dynamic cohort of geriatric surgical
educators and researchers who in turn created a vibrant body of educational tools
and scientific works that continue to advance the cause of improving medical care
of older adults.
PMID- 28513845
TI - Claud S. Rupert (1919-2017): The Father of DNA Repair.
PMID- 28513846
TI - A calmodulin-like protein regulates plasmodesmal closure during bacterial immune
responses.
AB - Plants sense microbial signatures via activation of pattern recognition receptors
(PPRs), which trigger a range of cellular defences. One response is the closure
of plasmodesmata, which reduces symplastic connectivity and the capacity for
direct molecular exchange between host cells. Plasmodesmal flux is regulated by a
variety of environmental cues but the downstream signalling pathways are poorly
defined, especially the way in which calcium regulates plasmodesmal closure.
Here, we identify that closure of plasmodesmata in response to bacterial
flagellin, but not fungal chitin, is mediated by a plasmodesmal-localized Ca2+
binding protein Calmodulin-like 41 (CML41). CML41 is transcriptionally
upregulated by flg22 and facilitates rapid callose deposition at plasmodesmata
following flg22 treatment. CML41 acts independently of other defence responses
triggered by flg22 perception and reduces bacterial infection. We propose that
CML41 enables Ca2+ -signalling specificity during bacterial pathogen attack and
is required for a complete defence response against Pseudomonas syringae.
PMID- 28513848
TI - Aspergillus fumigatus in cystic fibrosis: An update on immune interactions and
molecular diagnostics in allergic bronchopulmonary aspergillosis.
AB - A wide spectrum of pathological conditions may result from the interaction of
Aspergillus fumigatus and the immune system of its human host. Allergic
bronchopulmonary aspergillosis is one of the most severe A. fumigatus-related
diseases due to possible evolution toward pleuropulmonary fibrosis and
respiratory failure. Allergic bronchopulmonary aspergillosis occurs almost
exclusively in cystic fibrosis or asthmatic patients. An estimated 8%-10% of
patients with cystic fibrosis experience this condition. The diagnosis of
allergic bronchopulmonary aspergillosis relies on criteria first established in
1977. Progress in the understanding of host-pathogen interactions in A. fumigatus
and patients with cystic fibrosis and the ongoing validation of novel laboratory
tools concur to update and improve the diagnosis of allergic bronchopulmonary
aspergillosis.
PMID- 28513847
TI - Transmission characteristics of a two dimensional antiscatter grid prototype for
CBCT.
AB - AIM: High fraction of scattered radiation in cone-beam CT (CBCT) imaging degrades
CT number accuracy and visualization of low contrast objects. To suppress scatter
in CBCT projections, we developed a focused, two-dimensional antiscatter grid
(2DASG) prototype. In this work, we report on the primary and scatter
transmission characteristics of the 2DASG prototype aimed for linac mounted,
offset detector geometry CBCT systems in radiation therapy, and compared its
performance to a conventional one-dimensional ASG (1DASG). METHODS: The 2DASG is
an array of through-holes separated by 0.1 mm septa that was fabricated from
tungsten using additive manufacturing techniques. Through-holes' focusing
geometry was designed for offset detector CBCT in Varian TrueBeam system. Two
types of ASGs were evaluated: (a) a conventional 1DASG with a grid ratio of 10,
(b) the 2DASG prototype with a grid ratio of 8.2. To assess the scatter
suppression performance of both ASGs, Scatter-to-primary ratio (SPR) and scatter
transmission fraction (Ts) were measured using the beam stop method. Scatter and
primary intensities were modulated by varying the phantom thickness between 10
and 40 cm. Additionally, the effect of air gap and bow tie (BT) filter on SPR and
Ts were evaluated. Average primary transmission fraction (TP ) and pixel specific
primary transmission were also measured for both ASGs. To assess the effect of
transmission characteristics on projection image signal-to-noise ratio (SNR), SNR
improvement factor was calculated. Improvement in contrast to noise ratio (CNR)
was demonstrated using a low contrast object. RESULTS: In comparison to 1DASG,
2DASG reduced SPRs by a factor of 3 to 6 across the range of phantom setups
investigated. Ts values for 1D and 2DASGs were in the range of 21 to 29%, and 5
to 14% respectively. 2DASG continued to provide lower SPR and Ts at increased air
gap and with BT filter. Tp of 1D and 2DASGs were 70.6% and 84.7% respectively.
Due to the septal shadow of the 2DASG, its pixel specific primary transmission
values varied between 32.5% and 99.1%. With respect to 1DASG, 2DASG provided up
to factor of 1.7 more improvement in SNR across the SPR range investigated.
Moreover, 2DASG provided improved visualization of low contrast objects with
respect to 1DASG and NOASG setups. CONCLUSIONS: When compared to a conventional
1DASG, 2DASG prototype provided noticeably lower SPR and Ts values, indicating
its superior scatter suppression performance. 2DASG also provided 19% higher
average primary transmission that was attributed to the absence of interseptal
spacers and optimized grid geometry. Our results indicate that the combined
effect of lower scatter and higher primary transmission provided by 2DASG may
potentially translate into more accurate CT numbers and improved contrast
resolution in CBCT images.
PMID- 28513849
TI - Surgical considerations for papillary thyroid microcarcinomas.
AB - We reevaluate current treatment recommendations of papillary thyroid
microcarcinomas taking into account the indolent behavior of these tumors, and
the potential morbidity that may result from an unnecessary surgery. The goals of
this communication are to: 1) provide surgeons and endocrinologists with the most
up-to-date evidence on management of microcarcinomas, 2) outline appropriate
instances for active surveillance, and 3) describe the role of surgical
interventions for microcarcinomas including lobectomy, total thyroidectomy, and
central neck dissection.
PMID- 28513850
TI - Small prey species' behaviour and welfare: implications for veterinary
professionals.
AB - People have obligations to ensure the welfare of animals under their care.
Offences under the UK Animal Welfare Act are acts, or failures of action, causing
unnecessary suffering. Veterinary professionals need to be able to provide
current, scientifically based prophylactic advice, and respect the limits of
their expertise. The ethical concept of a life worth living and the Five Freedoms
are core to welfare. Behaviour is a central component, both influencing and
influenced by physical health. Owners frequently misunderstand the behaviour of
small prey mammals and how to meet their needs. This review provides insight into
the physical-social (external) and the cognitive-emotional (internal)
environments of small prey mammals, contextualised within an evolutionary
perspective. This is extrapolated to captivity and practical suggestions given
for meeting behavioural freedoms and enhancing client understanding and enjoyment
of their animals, thereby improving welfare.
PMID- 28513851
TI - Population Pharmacokinetics of Brentuximab Vedotin in Patients With CD30
Expressing Hematologic Malignancies.
AB - Brentuximab vedotin, a CD30-directed antibody-drug conjugate (ADC), is approved
for treating certain patients with CD30-expressing hematologic malignancies. Its
primary mechanism of action is the targeted delivery of a microtubule-disrupting
agent, monomethyl auristatin E (MMAE), to CD30-expressing cells. A population
pharmacokinetic (PopPK) analysis was conducted to characterize the PK of ADC and
unconjugated MMAE in patients with CD30-expressing hematologic malignancies by
compartmental analysis and to evaluate the effects of covariates on PK of the
ADC. A nonlinear mixed-effects modeling approach was used to evaluate data from
314 patients in 5 clinical studies. ADC PK was described by a linear, 3
compartment model with first-order elimination. MMAE PK was described by a
semimechanistic, linear, 2-compartment model with first-order elimination. The
estimated typical values for a 75-kg male patient were 1.56 L/d and 4.29 L for
ADC systemic clearance (CL) and volume of central compartment (V1), respectively,
with weight effect exponents of 0.698 and 0.503, respectively. Typical V1 in 75
kg females was 87% of that in males, with no impact on systemic ADC exposure.
Typical values of MMAE clearance (CLM ) and volume of central compartment (V4)
were 55.7 L/d and 79.8 L, respectively, with weight effect exponents fixed to
0.75 and 1.0, respectively. This is the first PopPK model of brentuximab vedotin
to semimechanistically link the PK of ADC and that of the unconjugated small
molecule MMAE. Both ADC and MMAE PK data were adequately described by the final
integrated model, which supports weight-based dosing of brentuximab vedotin in
adult patients with CD30-expressing hematologic malignancies.
PMID- 28513852
TI - Effect of Pentoxifylline in Ameliorating Myocardial Injury in Patients With
Myocardial Infarction Undergoing Thrombolytic Therapy: A Pilot Randomized
Clinical Trial.
AB - Cell death following acute myocardial infarction (MI) is the hallmark pathology
of cardiovascular disease, leading to considerable mortality and morbidity.
Platelet and neutrophil activation and inflammatory cytokines, prominently TNF
alpha, play an important role in the development of cell death. Because
pentoxifylline inhibits platelet and neutrophil activation and reduces TNF-alpha,
this study was performed to assess the potential benefit of pentoxifylline in the
reduction of myocardial injury following acute MI. In this randomized clinical
trial, 98 patients with acute MI were randomly divided into 2 groups. The
intervention group received an oral dose of 1200 mg of pentoxifylline immediately
before thrombolytic therapy (TLT). All patients received the same standard
protocol for treatment of MI. Cardiac enzymes were checked over 48 hours. ST
resolution was measured over 90 minutes. Then all patients were followed up for a
1-month period to assess major adverse cardiac effects (MACEs). There were no
significant differences in peak levels of CPK (P = .18) and CK-MB (P = .33)
between the 2 groups, whereas peak level of troponin I was significantly lower in
the pentoxifylline group (16.8 +/- 10.4 vs 21.3 +/- 11.6; P = .048). No
significant change between the groups was observed in biomarkers levels, ST
segment resolution, cardiac ejection fraction, and MACEs. The results showed that
pentoxifylline significantly reduced the peak value of troponin I in patients
with acute MI receiving TLT. No significant change was observed in the other
studied parameters. Further outcome-based studies are needed to show the clinical
relevance of differences between the groups in troponin peak.
PMID- 28513853
TI - Association between textural and morphological tumor indices on baseline PET-CT
and early metabolic response on interim PET-CT in bulky malignant lymphomas.
AB - PURPOSE: We investigated whether metabolic, textural, and morphological tumoral
indices evaluated on baseline PET-CT were predictive of early metabolic response
on interim PET-CT in a cohort of patients with bulky Hodgkin and non-Hodgkin
malignant lymphomas. METHODS: This retrospective study included 57 patients
referred for initial PET-CT examination. In-house dedicated software was used to
delineate tumor contours using a fixed 30% threshold of SUV max and then to
compute tumoral metabolic parameters (SUV max, mean, peak, standard deviation,
skewness and kurtosis, metabolic tumoral volume (MTV), total lesion glycolysis,
and area under the curve of the cumulative histogram), textural parameters
(Moran's and Geary's indices, energy, entropy, contrast, correlation derived from
the gray-level co-occurrence matrix, area under the curve of the power spectral
density, auto-correlation distance, and granularity), and shape parameters
(surface, asphericity, convexity, surfacic extension, and 2D and 3D fractal
dimensions). Early metabolic response was assessed on interim PET-CT using the
Deauville 5-point scale and patients were ranked according to the Lugano
classification as complete or not complete metabolic responders. The impact of
the segmentation method (alternate threshold at 41%) and image resolution
(Gaussian postsmoothing of 3, 5, and 7 mm) was investigated. The association of
the proposed parameters with early response was assessed in univariate and
multivariate analyses. Their added predictive value was explored using supervised
classification by support vector machines (SVM). We evaluated in leave-one-out
cross-validation three SVMs admitting as input features (a) MTV, (b) MTV +
histological type, and (c) MTV + histology + relevant texture/shape indices.
RESULTS: Features associated with complete metabolic response were low MTV (P =
0.01), low TLG (P = 0.003), high power spectral density AUC (P = 0.007), high
surfacic extension (P = 0.006), low 2D fractal dimension (P = 0.007), and low 3D
fractal dimension (P = 0.003). The prognostic value of these metrics was optimal
with the 30% segmentation threshold and overall was progressively altered with
decreasing image resolution. In cross-validation, the SVM accounting for texture
and shape achieved the highest predictive value with ROC AUC of 0.82 and 80%
accuracy (compared with 0.68 and 61% for MTV, and 0.65 and 68% for MTV +
histology). CONCLUSIONS: The combination of usual prognostic factors with
appropriately chosen textural and shape parameters evaluated on baseline PET-CT
improves the prediction of early metabolic response in bulky lymphoma.
PMID- 28513854
TI - Verification of dose profiles generated by the convolution algorithm of the gamma
knife(r) radiosurgery planning system.
AB - PURPOSE: A convolution algorithm that takes into account electron-density
inhomogeneity was recently introduced to calculate dose distributions for the
Gamma Knife (GK) PerfexionTM treatment planning program. The accuracies of the
dose distributions computed using the convolution method were assessed using an
anthropomorphic phantom and film dosimetry. METHODS: Absorbed-dose distributions
inside a phantom (CIRS Radiosurgery Head Phantom, Model 605) were calculated
using the convolution method of the GK treatment-planning software (Leksell Gamma
Plan(r) version 10.1; LGP) for various combinations of collimator size, location,
direction of calculation plane, and number of shots. Computed tomography (CT)
images of the phantom and a data set of CT number versus electron density were
provided to the LGP. Calculated distributions were exported as digital-image
communications in medicine-radiation therapy (DICOM-RT) files. Three types of
radiochromic film (GafChromic(r) MD-V2-55, MD-V3, and EBT2) were irradiated
inside the phantom using GK PerfexionTM. Scanned images of the measured films
were processed following standard radiochromic film-handling procedures. For a
two-dimensional quantitative evaluation, gamma index pass rates (GIPRs) and
normalized agreement-test indices (NATIs) were obtained. Image handling and index
calculations were performed using a commercial software package (DoseLab Pro
version 6.80). RESULTS: The film-dose calibration data were well fitted with
third-order polynomials (R2 >= 0.9993). The mean GIPR and NATI of the 93
analyzed films were 99.3 +/- 1.1% and 0.8 +/- 1.3, respectively, using 3%/1.0 mm
criteria. The calculated maximum doses were 4.3 +/- 1.7% higher than the measured
values for the 4 mm single shots and 1.8 +/- 0.7% greater than those for the 8 mm
single shots, whereas differences of only 0.3 +/- 0.9% were observed for the 16
mm single shots. The accuracy of the calculated distribution was not
statistically related to the collimator size, number of shots, or centrality of
location (P > 0.05, independent-sample t-test). The plans in the axial planes
exhibited poorer agreement with the measured distributions than the plans in the
coronal or sagittal planes; however, their GIPR values (>= 96.9%) were clinically
acceptable. The plans for an arbitrary virtual target of volume 1.6 cm3 at an
axial plane close to the top of the phantom showed the worst agreement and the
greatest fluctuation (GIPR = 96.9 +/- 1.2%, NATI = 3.9 +/- 1.7). CONCLUSIONS: The
measured accuracies of the dose distributions calculated by the convolution
algorithm of the LGP were within the clinically acceptable range (GIPR >= 96.9%)
for various configurations of collimator size, location, direction of calculation
plane, and number of shots. Due to the intrinsic asymmetry in the dose
distribution along the z-axis, the treatment plan should also be verified in
coronal or sagittal plane.
PMID- 28513855
TI - Technical Note: System for evaluating local hypothermia as a radioprotector of
the rectum in a small animal model.
AB - PURPOSE: The protective effects of induced or even accidental hypothermia on the
human body are widespread with several medical uses currently under active
research. In vitro experiments using human cell lines have shown hypothermia
provides a radioprotective effect that becomes more pronounced at large, single
fraction doses common to stereotactic body radiotherapy (SBRT) and stereotactic
radiosurgery (SRS) treatments. This work describes the development of a system to
evaluate local hypothermia for a radioprotective effect of the rat rectum during
a large dose of radiation relevant to prostate SBRT. This includes the evaluation
of a 3D-printed small animal rectal cooling device and the integration with a
small animal irradiator. METHODS: A 3-cm long, dual-lumen rectal temperature
control apparatus (RTCA) was designed in SOLIDWORKS CAD for 3D printing. The RTCA
was capable of recirculating flow in a device small enough for insertion into the
rat rectum, with a metal support rod for strength as well as visibility during
radiation treatment planning. The outer walls of the RTCA comprised of thin heat
shrink plastic, achieving efficient heat transfer into adjacent tissues.
Following leak-proof testing, fiber optic temperature probes were used to
evaluate the temperature over time when placed adjacent to the cooling device
within the rat rectum. MRI thermometry characterized the relative temperature
distribution in concentric ROIs surrounding the probe. Integration with an image
guided small animal irradiator and associated treatment planning system included
evaluation for imaging artifacts and effect of brass tubing on dose calculation.
RESULTS: The rectal temperature adjacent to the cooling device decreased from
body temperature to 15 degrees C within 10-20 min from device insertion and was
maintained at 15 +/- 3 degrees C during active cooling for the evaluated time of
one hour. MR thermometry revealed a steep temperature gradient with increasing
distance from the cooling device with the desired temperature range maintained
within the surrounding few millimeters. CONCLUSIONS: A 3D-printed rectal cooling
device was fabricated for the purpose of inducing local hypothermia in the rat
rectum. The RTCA was simply integrated with an image-guided small animal
irradiator and Monte Carlo-based treatment planning system to facilitate an in
vivo investigation of the radioprotective effect of hypothermia for late rectal
toxicity following a single large dose of radiation.
PMID- 28513856
TI - The Utility of a Population Approach in Drug-Drug Interaction Assessments: A
Simulation Evaluation.
AB - This study aims at evaluating the utility of the population pharmacokinetics
approach in therapeutic protein drug-drug-interaction (DDI) assessment.
Simulations were conducted for 2 representative victim drugs, methotrexate and
trastuzumab, using a parallel-group design with and without the interaction drug.
The effect of a perpetrator on the exposure of the victim drug is described as
the ratio of clearance/apparent clearance of the victim drug given with or
without the perpetrator. The power of DDI assessment was calculated as the
percentage of runs with 90% confidence interval of the estimated DDI effect
within 80% to 125% for the scenarios of no DDI, benchmarked with the
noncompartmental approach with intensive sampling. The impact of the number of
subjects, the number of sampling points per subject, sampling time error, and
model misspecification on the power of DDI determination were evaluated. Results
showed that with equal numbers of subjects in each arm, the population
pharmacokinetics approach with sparse sampling may need about the same or a
higher number of subjects compared to a noncompartmental approach in order to
achieve similar power. Increasing the number of subjects, even if only in the
study drug alone arm, can increase the power. Sampling or dosing time error had
notable impacts on the power for methotrexate but not for trastuzumab. Model
misspecification had no notable impacts on the power for trastuzumab. Overall,
the population pharmacokinetics approach with sparse sampling built in phase 2/3
studies allows appropriate DDI assessment with adequate study design and analysis
and can be considered as an alternative to dedicated DDI studies.
PMID- 28513857
TI - Angiogenesis during pregnancy: all routes lead to MAPKs.
PMID- 28513858
TI - An adaptive Fuzzy C-means method utilizing neighboring information for breast
tumor segmentation in ultrasound images.
AB - PURPOSE: Ultrasound (US) imaging has been widely used in breast tumor diagnosis
and treatment intervention. Automatic delineation of the tumor is a crucial first
step, especially for the computer-aided diagnosis (CAD) and US-guided breast
procedure. However, the intrinsic properties of US images such as low contrast
and blurry boundaries pose challenges to the automatic segmentation of the breast
tumor. Therefore, the purpose of this study is to propose a segmentation
algorithm that can contour the breast tumor in US images. METHODS: To utilize the
neighbor information of each pixel, a Hausdorff distance based fuzzy c-means
(FCM) method was adopted. The size of the neighbor region was adaptively updated
by comparing the mutual information between them. The objective function of the
clustering process was updated by a combination of Euclid distance and the
adaptively calculated Hausdorff distance. Segmentation results were evaluated by
comparing with three experts' manual segmentations. The results were also
compared with a kernel-induced distance based FCM with spatial constraints, the
method without adaptive region selection, and conventional FCM. RESULTS: Results
from segmenting 30 patient images showed the adaptive method had a value of
sensitivity, specificity, Jaccard similarity, and Dice coefficient of 93.60 +/-
5.33%, 97.83 +/- 2.17%, 86.38 +/- 5.80%, and 92.58 +/- 3.68%, respectively. The
region-based metrics of average symmetric surface distance (ASSD), root mean
square symmetric distance (RMSD), and maximum symmetric surface distance (MSSD)
were 0.03 +/- 0.04 mm, 0.04 +/- 0.03 mm, and 1.18 +/- 1.01 mm, respectively. All
the metrics except sensitivity were better than that of the non-adaptive
algorithm and the conventional FCM. Only three region-based metrics were better
than that of the kernel-induced distance based FCM with spatial constraints.
CONCLUSION: Inclusion of the pixel neighbor information adaptively in segmenting
US images improved the segmentation performance. The results demonstrate the
potential application of the method in breast tumor CAD and other US-guided
procedures.
PMID- 28513859
TI - Identification of a plasma miRNA biomarker signature for allergic asthma: A
translational approach.
AB - BACKGROUND: Asthma is a heterogeneous chronic disease with different phenotypes
and treatment responses. Thus, there is a high clinical need for molecular
disease biomarkers to aid in differentiating these distinct phenotypes. As
MicroRNAs (miRNAs), that regulate gene expression at the post-transcriptional
level, are altered in experimental and human asthma, circulating miRNAs are
attractive candidates for the identification of novel biomarkers. This study
aimed to identify plasmatic miRNA-based biomarkers of asthma, through a
translational approach. METHODS: We prescreened miRNAs in plasma samples from two
different murine models of experimental asthma (ovalbumin and house dust mite);
miRNAs deregulated in both models were further tested in a human training cohort
of 20 asthma patients and 9 healthy controls. Candidate miRNAs were then
validated in a second, independent group of 26 asthma patients and 12 healthy
controls. RESULTS: Ten miRNA ratios consisting of 13 miRNAs were differentially
regulated in both murine models. Measuring these miRNAs in the training cohort
identified a biomarker signature consisting of five miRNA ratios (7 miRNAs). This
signature showed a good sensitivity and specificity in the test cohort with an
area under the receiver operating characteristic curve (AUC) of 0.92. Correlation
of miRNA ratios with clinical characteristics further revealed associations with
FVC % predicted, and oral corticosteroid or antileukotriene use. CONCLUSION:
Distinct plasma miRNAs are differentially regulated both in murine and in human
allergic asthma and were associated with clinical characteristics of patients.
Thus, we suggest that miRNA levels in plasma might have future potential to
subphenotype patients with asthma.
PMID- 28513861
TI - Regulatory and Ethical Issues in Pediatric Clinical Research: Recommendations
From a Panel Discussion.
PMID- 28513860
TI - Cortical contributions to sensory gating in the ipsilateral somatosensory cortex
during voluntary activity.
AB - KEY POINTS: It has long been known that the somatosensory cortex gates sensory
inputs from the contralateral side of the body. Here, we examined the
contribution of the ipsilateral somatosensory cortex (iS1) to sensory gating
during index finger voluntary activity. The amplitude of the P25/N33, but not
other somatosensory evoked potential (SSEP) components, was reduced during
voluntary activity compared with rest. Interhemispheric inhibition between S1s
and intracortical inhibition in the S1 modulated the amplitude of the P25/N33.
Note that changes in interhemispheric inhibition between S1s correlated with
changes in cortical circuits in the ipsilateral motor cortex. Our findings
suggest that cortical circuits, probably from somatosensory and motor cortex,
contribute to sensory gating in the iS1 during voluntary activity in humans.
ABSTRACT: An important principle in the organization of the somatosensory cortex
is that it processes afferent information from the contralateral side of the
body. The role of the ipsilateral somatosensory cortex (iS1) in sensory gating in
humans remains largely unknown. Using electroencephalographic (EEG) recordings
over the iS1 and electrical stimulation of the ulnar nerve at the wrist, we
examined somatosensory evoked potentials (SSEPs; P14/N20, N20/P25 and P25/N33
components) and paired-pulse SSEPs between S1s (interhemispheric inhibition) and
within (intracortical inhibition) the iS1 at rest and during tonic index finger
voluntary activity. We found that the amplitude of the P25/N33, but not other
SSEP components, was reduced during voluntary activity compared with rest.
Interhemispheric inhibition increased the amplitude of the P25/N33 and
intracortical inhibition reduced the amplitude of the P25/N33, suggesting a
cortical origin for this effect. The P25/N33 receives inputs from the motor
cortex, so we also examined the contribution of distinct sets of cortical
interneurons by testing the effect of ulnar nerve stimulation on motor-evoked
potentials (MEPs) elicited by transcranial magnetic stimulation over the
ipsilateral motor cortex with the coil in the posterior-anterior (PA) and
anterior-posterior (AP) orientation. Afferent input attenuated PA, but not AP,
MEPs during voluntary activity compared with rest. Notably, changes in
interhemispheric inhibition correlated with changes in PA MEPs. Our novel
findings suggest that interhemispheric projections between S1s and intracortical
circuits, probably from somatosensory and motor cortex, contribute to sensory
gating in the iS1 during voluntary activity in humans.
PMID- 28513862
TI - Liver transplantation for unresectable colorectal liver metastases: A systematic
review.
AB - The use of liver transplantation (LT) for liver metastases attempted in the early
1990's was associated with poor perioperative outcomes and unacceptably low
overall survival. Recently, there has been renewed interest in LT as a treatment
option for colorectal liver metastases (CLM) in countries where organ supply is
high. To date, no meticulous analysis about the efficacy, safety and outcomes of
LT in CLM patients has been published. We present the first systematic review on
the subject.
PMID- 28513863
TI - Relative contributions of maternal Western-type high fat, high sugar diets and
maternal obesity to altered metabolic function in pregnancy.
PMID- 28513864
TI - The influence of non-rigid anatomy and patient positioning on endoscopy-CT image
registration in the head and neck.
AB - PURPOSE: To assess the influence of non-rigid anatomy and differences in patient
positioning between CT acquisition and endoscopic examination on endoscopy-CT
image registration in the head and neck. METHODS: Radiotherapy planning CTs and
31-35 daily treatment-room CTs were acquired for nineteen patients. Diagnostic
CTs were acquired for thirteen of the patients. The surfaces of the airways were
segmented on all scans and triangular meshes were created to render virtual
endoscopic images with a calibrated pinhole model of an endoscope. The virtual
images were used to take projective measurements throughout the meshes, with
reference measurements defined as those taken on the planning CTs and test
measurements defined as those taken on the daily or diagnostic CTs. The influence
of non-rigid anatomy was quantified by 3D distance errors between reference and
test measurements on the daily CTs, and the influence of patient positioning was
quantified by 3D distance errors between reference and test measurements on the
diagnostic CTs. The daily CT measurements were also used to investigate the
influences of camera-to-surface distance, surface angle, and the interval of time
between scans. RESULTS: Average errors in the daily CTs were 0.36 +/- 0.61 cm in
the nasal cavity, 0.58 +/- 0.83 cm in the naso- and oropharynx, and 0.47 +/- 0.73
cm in the hypopharynx and larynx. Average errors in the diagnostic CTs in those
regions were 0.52 +/- 0.69 cm, 0.65 +/- 0.84 cm, and 0.69 +/- 0.90 cm,
respectively. All CTs had errors heavily skewed towards 0, albeit with large
outliers. Large camera-to-surface distances were found to increase the errors,
but the angle at which the camera viewed the surface had no effect. The errors in
the Day 1 and Day 15 CTs were found to be significantly smaller than those in the
Day 30 CTs (P < 0.05). CONCLUSIONS: Inconsistencies of patient positioning have a
larger influence than non-rigid anatomy on projective measurement errors. In
general, these errors are largest when the camera is in the superior pharynx,
where it sees large distances and a lot of muscle motion. The errors are larger
when the interval of time between CT acquisitions is longer, which suggests that
the interval of time between the CT acquisition and the endoscopic examination
should be kept short. The median errors found in this study are comparable to
acceptable levels of uncertainty in deformable CT registration. Large errors are
possible even when image alignment is very good, indicating that projective
measurements must be made carefully to avoid these outliers.
PMID- 28513865
TI - Diagnosis of Tuberculosis in HIV Co-infected Individuals: Current Status,
Challenges and Opportunities for the Future.
AB - Tuberculosis (TB) remains one of the most important causes of death among people
co-infected with human immunodeficiency virus (HIV). The diagnosis of TB remains
challenging in HIV co-infected individuals, due to a high frequency of smear
negative disease and high rates of extrapulmonary TB. Accurate, ease of use and
rapid diagnosis of active TB are critical to the World Health Organization (WHO)
End TB Strategy by 2050. Traditional laboratory techniques do not provide rapid
and accurate results to effectively manage HIV co-infected patients. Over the
last decade, molecular methods have provided significant steps in the fight
against TB. However, many HIV co-infected patients do not have access to these
molecular diagnostic tests. Given the costs closely related with confirming a TB
diagnosis in HIV patients, an overtreatment for TB is used in this patient
population. Nowadays, an estimated US $8 billion a year is required to provide TB
treatment, which is very high compared with making an important strategy to
improve the current diagnostic tests. This review focuses on current advances in
diagnosing active TB with an emphasis on the diagnosis of HIV-associated TB. Also
discussed are the main challenges that need to be overcome for improving an
adequate initial diagnosis of active TB in HIV-positive patients.
PMID- 28513866
TI - LncRNA PTCSC3/miR-574-5p Governs Cell Proliferation and Migration of Papillary
Thyroid Carcinoma via Wnt/beta-Catenin Signaling.
AB - The distance metastases of papillary thyroid carcinoma (PTC) were a major
threaten for PTC patients, thus, to study the potential mechanism for the
treatment of PTC was essential. Previous studies have shown that PTCSC3 (Thyroid
Carcinoma Susceptibility Candidate 3), miR-574-5p and Wnt/beta-catenin were
involved in PTC, but the potential pathogenic mechanism among them was still
unclear. Real-time PCR and Western blot were used to detect genes expression.
Luciferase reporter assay was used to detect the combination of miR-574-5p and
suppressor of cancer cell invasion (SCAI), as well as the ratio of TOP/FOP. RNA
Pull-down assay verified the bound of PTCSC3 and miR-574-5p. MTT assay, Transwell
assay, and wound scratch assay were used to detect cell viability and cell
migration. The expression of PTCSC3 and SCAI were decreased, while miR-574-5p and
beta-catenin were increased in PTC tissues and cells. Overexpressed PTCSC3
suppressed cell proliferation and migration, promoted the expression of SCAI, but
inhibited beta-catenin. PTCSC3 absorbed miR-574-5p, and miR-574-5p targeted to
SCAI; SCAI could regulate the activity of Wnt/beta-catenin. PTCSC3/miR-574-5p
regulated the activity of Wnt/beta-catenin via SCAI and mediated cell
proliferation and migration of PTC-1. In vivo experiments verified the fact that
overexpressed PTCSC3 inhibited tumor growth. The signaling PTCSC3-miR-574-5p-SCAI
Wnt/beta-catenin mediated the proliferation and migration of PTC-1 cells, which
was vital for the further PTC therapy and prognosis. J. Cell. Biochem. 118: 4745
4752, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28513867
TI - The Role of Circulating T Follicular Helper Cells and Regulatory Cells in Non
Small Cell Lung Cancer Patients.
AB - T follicular helper (Tfh) cells and T follicular regulatory (Tfr) cells are
identified as the new subset of immune cells. This study aims to investigate the
role of circulating Tfh cells (cTfh) and Tfr (cTfr) cells in the pathogenesis of
non-small cell lung cancer (NSCLC). A total of 27 NSCLC patients and 19 age and
sex-matched healthy controls were enrolled. The percentage of cTfh and cTfr was
detected by flow cytometric analysis. Compared to healthy controls, a
significantly higher percentage of both cTfh and cTfr cells were observed in
NSCLC patients (for cTfh, 18.88% +/- 16.84% versus 5.98% +/- 3.70%, P < 0.01; for
cTfr, 2.67% +/- 2.20% versus 1.14% +/- 0.76%, P < 0.01). Furthermore, there was a
positive correlation between cTfh/cTfr ratio and age in NSCLC patients (P <
0.05). When taking age 60 as a cut-off, the percentage of both cTfh cells and
cTfr cells were higher in older patients than younger patients. Moreover, our
data showed there was lower percentage of cTfh cells in NSCLC patients with early
stage disease (I and II) (12.10% +/- 12.22%) than that in advanced stage disease
(III and IV) (30.41% +/- 17.87%) (P < 0.01). However, no significant relationship
was observed between cTfr cells and clinical stage in NSCLC patients. A higher
percentage of cTfh cells was observed in patients with squamous cell carcinoma
compared with adenocarcinoma (31.70% +/- 20.73% versus. 13.48% +/- 11.78%, P <
0.05). Taken together, there was significantly higher percentage of cTfh and cTfr
cells in NSCLC patients. cTfh and cTfr cells might play an important role in the
pathogenesis of NSCLC patients.
PMID- 28513868
TI - HER2 assessment in locally advanced gastric cancer: comparing the results
obtained with the use of two primary tumour blocks versus those obtained with the
use of all primary tumour blocks.
AB - AIMS: HER2 is currently the only biomarker used to select eligible patients with
advanced gastric cancer (GC) for targeted therapy. The aims of this study were to
verify the value of dual-block HER2 assessment and to explore whether increasing
the block number is more beneficial by carrying out a randomized prospective
cohort study in which dual-block and all-block HER2 assessment were compared in
resected specimens of GC. METHODS AND RESULTS: Five hundred and forty-nine
resected GC specimens were randomly enrolled into two cohorts: a dual-block group
(n = 274) with two primary tumour blocks tested, and an all-block group (n = 275)
with all primary tumour blocks tested. Immunohistochemical staining of HER2 was
performed. For HER2-equivocal (2+) cases, fluorescence in-situ hybridization
(FISH) was performed. As compared with single-block assessment, dual-block
assessment increased the HER2 immunohistochemistry (IHC)-positive (3+) rate. The
rate with dual-block assessment (11.3%) was significantly higher than that with
block 1 assessment (8.8%) (P = 0.016) and block 2 assessment (9.1%) (P = 0.031).
Similarly, all-block assessment demonstrated a higher HER2 3+ rate (12.4%) than
single-block assessment (block 1, 6.5%; block 2, 6.2%; block 3, 7.2%; block 4,
8.7%) (P < 0.05). HER2 3+ rates of all-block and dual-block assessments showed no
significant difference (P = 0.703). After IHC and FISH results had been combined,
the HER2-positive rate with all-block assessment (13.5%) was slightly higher than
that with dual-block assessment (12.0%), although the difference was not
statistically significant (P = 0.62). CONCLUSIONS: Dual-block immunohistochemical
assessment is an effective, practical and economic approach that is suitable for
the preliminary screening of HER2. We recommend that dual-block HER2 assessment
be routinely performed on resected specimens of GC. All-block assessment can be a
supplement to dual-block assessment if necessary.
PMID- 28513869
TI - Transition of Intravenous Treprostinil to Oral Therapy in a Patient with
Functional Class IV Chronic Thromboembolic Pulmonary Hypertension.
AB - Chronic thromboembolic pulmonary hypertension (CTEPH) occurs when pulmonary
emboli fail to resolve with anticoagulation. For patients with inoperable or
residual CTEPH, riociguat is currently the only therapy approved by the United
States Food and Drug Administration. However, some patients with CTEPH may
require therapy beyond riociguat, such as intravenous prostacyclins, which can
present significant administration challenges in patients with complex comorbid
conditions. We describe a 42-year-old man with T12 paraplegia complicated by
CTEPH (functional class IV with substantial right ventricular dysfunction) and
severe pressure ulcers. In order to facilitate goals of care (hospital discharge
to a skilled nursing facility where parenteral prostanoids could not be
administered), he underwent rapid transition from intravenous treprostinil to
oral selexipag in the form of a cross-taper over 6 days. The patient required
readmission due to worsening symptoms and was transitioned back to intravenous
treprostinil; he tolerated conversion to oral treprostinil for approximately 4
months, but it was subsequently discontinued due to nausea and modified goals of
care. The patient underwent transition to hospice care 3 months later and
eventually died from clinical deterioration. To our knowledge, this is the first
report to describe transition from intravenous treprostinil to selexipag as well
as conversion from parenteral treprostinil to oral treprostinil in a patient with
CTEPH and illustrates the approaches to and potential issues with prostanoid
transitions. Additional observations are necessary to better understand the
relative roles of selexipag and oral treprostinil regarding comparative efficacy
and tolerability.
PMID- 28513870
TI - Activation of the Nrf2-ARE Signaling Pathway Prevents Hyperphosphatemia-Induced
Vascular Calcification by Inducing Autophagy in Renal Vascular Smooth Muscle
Cells.
AB - This study investigates the effect of nuclear factor erythroid 2-related factor 2
antioxidant response element (Nrf2-ARE) signaling pathway in vascular
calcification (VC) via inducing Autophagy in renal vascular smooth muscle cells
(VSMCs). VSMCs were assigned into six experimental groups: the normal control,
high phosphorus, si-negative control (si-NC), Nrf2-siRNA, over-expressed Nrf2,
and negative control (NC) groups. RT-PCR was applied to detect the mRNA
expressions of the desired Nrf2-ARE signaling pathway-related genes (Nrf2, NQO-1,
HO-1, gamma-GCS). The protein products of these genes: apoptosis-related genes
(LC3I and LC3II), osteogenic marker proetins (Runt-related transcription factor
2) Runx2 and BMP2 were all detected by Western blotting. Autophagosomes in VSMCs
were observed under a transmission electron microscope. We discovered an
increased calcium ion concentration and upregulated Runx2, BMP2, Nrf2, HO-1,
gamma-GCS, NQO-1, and LC3II/LC3I expressions in the high phosphorous, si-NC and
Nrf2-siRNA, and NC groups, compared with the normal control group. Compared to
the high phosphorus and si-NC groups, higher levels of Runx2 and BMP2 but
decreased Nrf2, HO-1, gamma-GCS, NQO-1, and LC3II/LC3I expressions were detected
in the Nrf2-siRNA group. The high phosphorus, si-NC and over-expressed Nrf2
experimental groups all had increased Nrf2, NQO-1, HO-1, gamma-GCS, and
LC3II/LC3I expressions as well as high numbers of autophagosomes compared with
the normal control group. Finally, we detected a lower amount of autophagosomes
presence and Nrf2, NQO-1, HO-1 gamma-GCS, and LC3II/LC3 protein expression of
Nrf2-siRNA group than that of the high phosphorus and si-NC groups. Activation of
Nrf2-ARE signaling pathway may prevent hyperphosphatemia-induced VC by inducing
autophagy in VSMCs. J. Cell. Biochem. 118: 4708-4715, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28513871
TI - Potential Role of Long Non-Coding RNA ANRIL in Pediatric Medulloblastoma Through
Promotion on Proliferation and Migration by Targeting miR-323.
AB - Medulloblastoma (MB) is a common primary tumor of the central nervous system
diagnosed in pediatric patients. Survivors of MB are frequently accompanied by
severe side effects, thus it is urgent to explore novel therapeutic target. First
of all, the level of antisense non-coding RNA in the INK4 locus (ANRIL) in normal
cerebellum and DAOY cells were evaluated. Then, the effect of ANRIL on DAOY cell
proliferation, migration, and apoptosis were tested. Then, qRT-PCR was performed
to explore whether ANRIL acted as a sponge of miR-323. The effects of miR-323
inhibition on ANRIL silence-induced alterations of cell proliferation, migration,
and apoptosis were estimated. Predicted by TargetScan, the possible target gene
of miR-323 was screened, followed by validation with luciferase assay. The
abnormally expressed BRI3 on cell proliferation, migration, apoptosis, and
signaling pathways were all evaluated. ANRIL was up-regulated in MB and its
silence significantly lowered cell viability and migration but promoted cell
apoptosis. ANRIL acted as a sponge of miR-323 and its silence functioned through
up-regulating miR-323. BRI3 and CDK6 were target genes of miR-323 and the effect
of BRI3 on DAOY cells was the same as ANRIL. Moreover, ANRIL suppression could
reduce phosphorylated levels of p38 MAPK, ERK and AKT, and inhibit Wnt signaling
pathway through positively regulating BRI3. ANRIL inhibition repressed cell
proliferation and migration but promoted cell apoptosis through miR-323-mediated
regulation of BRI3, which could activate p38 MAPK, ERK, and AKT as well as Wnt
signaling pathway. J. Cell. Biochem. 118: 4735-4744, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28513872
TI - Nucleophosmin Regulates Intracellular Oxidative Stress Homeostasis via
Antioxidant PRDX6.
AB - Reactive oxygen species (ROS) play both deleterious and beneficial roles in
cancer cells. Nucleophosmin (NPM) is heavily implicated in cancers of diverse
origins, being its gene over-expression in solid tumors or frequent mutations in
hematological malignancies. However, the role and regulatory mechanism of NPM in
oxidative stress are unclear. Here, we found that NPM regulated the expression of
peroxiredoxin 6 (PRDX6), a member of thiol-specific antioxidant protein family,
consequently affected the level and distribution of ROS. Our data indicated that
NPM knockdown caused the increase of ROS and its relocation from cytoplasm to
nucleoplasm. In contrast, overexpression or cytoplasmic localization of NPM
upregulated PRDX6, and decreased ROS. In addition, NPM knockdown decreased
peroxiredoxin family proteins, including PRDX1, PRDX4, and PRDX6. Co
immunoprecipitation further confirmed the interaction between PRDX6 and NPM.
Moreover, NSC348884, an inhibitor specifically targeting NPM oligomerization,
decreased PRDX6 and significantly upregulated ROS. These observations
demonstrated that the expression and localization of NPM affected the homeostatic
balance of oxidative stress in tumor cells via PRDX6 protein. The regulation axis
of NPM/PRDX/ROS may provide a novel therapeutic target for cancer treatment. J.
Cell. Biochem. 118: 4697-4707, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28513874
TI - beta3-Adrenergic Regulation of EPC Features Through Manipulation of the Bone
Marrow MSC Niche.
AB - Mesenchymal stem cells (MSCs) reside in a specific niche in the bone marrow,
however, biological features of this niche are still not fully understood. Given
the interactions of MSCs with endothelial cells in different tissues, bone marrow
MSC niche may influence the biological features of endothelial progenitor cells
(EPCs). To understand the role of the sympathetic nervous system in regulation of
the MSC niche, we examined whether the manipulation of the MSC niche via beta3
adrenergic signals will affect EPC features. A selective beta3 agonist (BRL37344)
or a beta3 antagonist (SR59230A) was administered in mice for 2 weeks to
determine the potential effects of these regimens on the population of CD133+
stem cells in the bone marrow. Then, bone marrow-derived MSCs and EPCs were
harvested and expanded from the mice to examine the effect of changes in the MSC
niche on EPC features. Improved MSC colony forming potency with increased bone
marrow stromal cell-derived factor 1 (SDF-1) (also known as C-X-C motif chemokine
12 [CXCL12]) expression was shown as a result of intensification of the bone
marrow adrenergic signals through BRL37344 injection. On the other hand, the
blockage of these signals limited the expression level of SDF-1 and resulted in
bone marrow enrichment of CD133+ cells. Manipulation of the MSC niche and
decreased SDF-1 expression via SR59230A injection also prompted EPCs to form more
colonies with augmented proliferation and differentiation capacity. Overall, our
results indicate that the beta3-adrenergic signals regulate the MSC niche,
thereby resulting in modulation of EPC biological features. J. Cell. Biochem.
118: 4753-4761, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28513875
TI - Incidence, clinicopathological features and fusion transcript landscape of
translocation renal cell carcinomas.
PMID- 28513873
TI - Myxoid fibroadenomas differ from conventional fibroadenomas: a hypothesis
generating study.
AB - AIMS: Breast myxoid fibroadenomas (MFAs) are characterized by a distinctive
hypocellular myxoid stroma, and occur sporadically or in the context of Carney
complex, an inheritable condition caused by PRKAR1A-inactivating germline
mutations. Conventional fibroadenomas (FAs) are underpinned by recurrent MED12
mutations in the stromal components of the lesions. The aim of this study was to
investigate the genomic landscape of MFAs and compare it with that of
conventional FAs. METHODS AND RESULTS: Eleven MFAs from patients without clinical
and/or genetic evidence of Carney complex were retrieved. DNA samples of tumour
and matching normal tissue were subjected to massively parallel sequencing using
the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer
Targets (MSK-IMPACT) assay, an assay targeting 410 cancer genes. Genetic
alterations detected by MSK-IMPACT were tested in samples in which the stromal
and epithelial components were separately laser capture-microdissected.
Sequencing revealed no germline PRKAR1A mutations and non-synonymous mutations in
six MFAs. Interestingly, in three of the MFAs in which the stromal and epithelial
components were separately microdissected, the mutations were found to be
restricted to the epithelial rather than the stromal component. The sole
exception was a lesion harbouring a somatic truncating PRKAR1A mutation. Upon
histological re-review, this case was reclassified as a breast myxoma, consistent
with the spectrum of tumous observed in Carney complex patients. In this case,
the PRKAR1A somatic mutation was restricted to the stromal component. CONCLUSION:
MFAs lack MED12 mutations, and their stromal components seem not to harbour
mutations in the 410 cancer genes tested. Whole-exome and/or whole-genome
analyses of MFAs are required to elucidate their genetic drivers.
PMID- 28513876
TI - The inter-play between facilitation and context in the promoting action on
research implementation in health services framework: A qualitative exploratory
implementation study embedded in a cluster randomized controlled trial to reduce
restraint in nursing homes.
AB - AIM: To explore the inter-play between external facilitation and nursing home
contexts relative to intervention outcomes. BACKGROUND: The Promoting Action on
Research Implementation in Health Services framework is frequently used to
theoretically inform implementation and research in nursing and recent reviews
indicate high face validity for health services. However, the inter-play and
relationship between framework sub-elements of evidence, context and facilitation
and the prospective utility in non-English speaking contexts warrant further
illumination. DESIGN: In an overarching single-blind cluster-randomized
controlled trial, we applied participatory action research and ethnography from
August 2011-June 2015 to evaluate a standardized education intervention to reduce
restraint and agitation in nursing home residents living with dementia. The trial
results are published elsewhere. METHODS: Prospectively informed by the PARIHS
framework, a research team and eight facilitators participating in dual roles as
action researchers designed, implemented, and evaluated the intervention. How
contextual factors influenced the facilitation processes were explored in focus
group interviews (1), reflection notes (84) written by the facilitators' after
each education session, ethnographic field studies (6 homes), and co-analysis
workshops (5). Directed content analysis was used to analyse data. RESULTS:
Clinical leaders taking roles of internal facilitator influenced the success of
implementation, while complex and fluctuating context elements determined whether
restraint use was reduced- or not. The PARIHS framework was found to be relevant
in a non-English nursing home setting, albeit some elements merit further
conceptualization. CONCLUSIONS: Our findings confirm the prospective utility of
the PARIHS framework for implementation in a non-English context, particularly
the notion of implementation processes as dynamic and multifaceted.
PMID- 28513877
TI - Heart rate and outcome in heart failure with reduced ejection fraction:
Differences between atrial fibrillation and sinus rhythm-A CIBIS II analysis.
AB - BACKGROUND: Heart rate has been associated with prognosis in patients with heart
failure with reduced ejection fraction (HFREF) and sinus rhythm; whether this
also holds true in patients with atrial fibrillation (AF) is unknown. HYPOTHESIS:
To evaluate cardiac rhythm and baseline heart rate and the influence of outcome
in patients with HFREF enrolled in the Cardiac Insufficiency Bisoprolol Study II.
METHODS: In total, 2539 patients were stratified according to their baseline
heart rhythm (AF or sinus rhythm) and into quartiles of heart rate (<=70 bpm, 71
78 bpm, 79-90 bpm, and >90 bpm). The primary outcome was all-cause mortality.
Mean follow-up was 1.3 years. RESULTS: Mean age was 61 years, mean left
ventricular ejection fraction was 28%, and 80% were male. A total of 521 (21%)
patients had AF at baseline. The risk associated with all-cause mortality for
each 5 bpm increase in heart rate in patients with sinus rhythm (hazard ratio
[HR]: 1.06, 95% confidence interval [CI]: 1.01-1.11, P = 0.012) was significantly
different from those with AF (HR: 1.00, 95% CI: 0.94-1.07, P = 0.90, P for
interaction = 0.041). The risk associated with higher heart rate in sinus rhythm
was primarily attributable to excess risk in the highest quartile (HR: 1.64, 95%
CI: 1.18-2.30, P = 0.003). Allocation to bisoprolol did not modify the
interaction between heart rate, rhythm and outcome. CONCLUSIONS: In HFREF
patients with AF, a higher heart rate is not associated with increased event
rates in contrast to HFREF patients with sinus rhythm.
PMID- 28513878
TI - Gene cloning, expression, and characterization of trehalose-6-phosphate synthase
from Pleurotus ostreatus.
AB - Trehalose-6-phosphate synthase (TPS; EC2.4.1.15) catalyzes the first step in
trehalose synthesis, which involves transfer of glucose from uridine diphosphate
glucose (UDPG) to glucose 6-phosphate (G6P) to form trehalose-6-phosphate. To
determine the gene and enzymatic characteristics of TPS in Pleurotus ostreatus,
we cloned and sequenced the cDNA of PoTPS1, which contains a 1665 bp open reading
frame that encodes a 554-amino acid protein with a predicted molecular weight of
62.01 kDa. This gene was expressed in Escherichia coli BL21 and then the
recombinant protein was purified and characterized. Results showed that the
optimum pH and temperature for the recombinant PoTPS1 were 7.4 and 30 degrees C,
respectively; the Km value against G6P and UDPG were 0.14 and 0.17 mM,
respectively, and the Vmax and Kcat values were 91.86 nkat/g and 5.89 s-1 ,
respectively. Trehalose content was as high as 158.88 mg g-1 dry weight after
heat treatment at 40 degrees C for 15 h, which was consistent with highest TPS1
activity at that time point. This result indicated that PoTPS1 was responsible
for trehalose synthesis in P. ostreatus.
PMID- 28513879
TI - The Therapeutic Potential of PI3K/Akt/mTOR Inhibitors in Breast Cancer: Rational
and Progress.
AB - Breast cancer (BC) is the most commonly diagnosed cancer in women. The
PI3K/AKT/mTOR pathway is among the most frequently dysregulated pathways in
patients with BC. The activation of this pathway is associated with increased
cell growth and clinical outcome, and its overexpression is associated with a
poor prognosis. It has been proposed that it may be of importance as a potential
therapeutic target in the treatment of BC. The aim of current review is to
provide an overview of the potential utility of PI3K/Akt/mTOR inhibitors in
patients with BC, with particular emphasis on recent preclinical and clinical
studies. J. Cell. Biochem. 119: 213-222, 2018. (c) 2017 Wiley Periodicals, Inc.
PMID- 28513880
TI - Unstable rocker shoes promote recovery from marathon-induced muscle damage in
novice runners.
AB - We recently reported that wearing unstable rocker shoes (Masai Barefoot
Technology: MBT) may enhance recovery from marathon race-induced fatigue.
However, this earlier study only utilized a questionnaire. In this study, we
evaluated MBT utilizing objective physiological measures of recovery from
marathon-induced muscle damages. Twenty-five university student novice runners
were divided into two groups. After running a full marathon, one group wore MBT
shoes (MBT group), and the control group (CON) wore ordinary shoes daily for 1
week following the race. We measured maximal isometric joint torque, muscle
hardness (real time tissue elastography of the strain ratio) in the lower limb
muscles before, immediately after, and 1, 3, and 8 days following the marathon.
We calculated the magnitude of recovery by observing the difference in each value
between the first measurement and the latter measurements. Results showed that
isometric torques in knee flexion recovered at the first day after the race in
the MBT group while it did not recover even at the eighth day in the CON group.
Muscle hardness in the gastrocnemius and vastus lateralis showed enhanced
recovery in the MBT group in comparison with the CON group. Also for muscle
hardness in the tibialis anterior and biceps femoris, the timing of recovery was
delayed in the CON group. In conclusion, wearing MBT shoes enhanced recovery in
lower leg and thigh muscles from muscle damage induced by marathon running.
PMID- 28513883
TI - Protein Reduction and Dialysis-Free Work-Up through Phosphines Immobilized on a
Magnetic Support: TCEP-Functionalized Carbon-Coated Cobalt Nanoparticles.
AB - Tris(2-carboxyethyl)phosphine (TCEP) is an often-used reducing agent in
biochemistry owing to its selectivity towards disulfide bonds. As TCEP causes
undesired consecutive side reactions in various analytical methods (e.g., gel
electrophoresis, protein labeling), it is usually removed by means of dialysis or
gel filtration. Here, an alternative method of separation is presented, namely
the immobilization of TCEP on magnetic nanoparticles. This magnetic reagent
provides a simple and rapid approach to remove the reducing agent after
successful reduction. A reduction capacity of 70 MUmol per gram of particles was
achieved by using surface-initiated atom transfer polymerization.
PMID- 28513881
TI - Base-Modified Nucleic Acids as a Powerful Tool for Synthetic Biology and
Biotechnology.
AB - The ability of various nucleoside triphosphate analogues of deoxyguanosine and
deoxycytidine with 7-deazadeoxyadenosine (A1 ) and 5-chlorodeoxyuridine (T1 ) to
serve as substrates for Taq DNA polymerase was evaluated. The triphosphate set
composed of A1 , T1 , and 7-deazadeoxyguanosine with either 5-methyldeoxycytidine
or 5-fluorodeoxycytidine was successfully employed in the polymerase chain
reaction (PCR) of 1.5 kb fragments as well as random oligonucleotide libraries.
Another effective combination of triphosphates for the synthesis of a 1 kb PCR
product was A1 , T1 , deoxyinosine, and 5-bromodeoxycytidine. In vivo experiments
using an antibiotic-resistant gene containing the latter set demonstrated that
the bacterial machinery accepts fully modified sequences as genetic templates.
Moreover, the ability of the base-modified segments to selectively protect DNA
from cleavage by restriction endonucleases was shown. This approach can be used
to regulate the endonuclease cleavage pattern.
PMID- 28513882
TI - Imaging Nanoscale Morphology of Semiconducting Polymer Films with Photoemission
Electron Microscopy.
AB - Photoemission electron microscopy in combination with polarized laser light is
presented as a tool permitting direct imaging of polymer-chain orientation and
local degree of order in semicrystalline samples of semiconducting polymers, a
promising class of materials for future electronics. The key advantages of this
imaging tool are its nondestructive and fast measurements, straightforward data
analysis, the low complexity of sample preparation, and the possibility of
performing measurements on a broad variety of technologically relevant
substrates. The high spatial resolution of the microscope provides insights into
the nanoscale morphology, which is relevant for the material's performance in
electronic devices.
PMID- 28513885
TI - Biomechanical function of a balloon nucleus pulposus replacement system: A human
cadaveric spine study.
AB - With recent advances in motion-sparing techniques in spine surgery, disc nucleus
replacement (DNR) has been introduced as a viable method to restore the
biomechanical functions of the spine. Several methods of DNR have been proposed
in the literature. However, the risk of device migration or extrusion is a major
issue that should be addressed for a successful DNR. DNR using a balloon nucleus
(BN) filled with pressurized fluid may be capable of reducing such risks while
preserving the advantages of DNR. The objective of this study was to investigate
the biomechanical functionalities of the human cadaveric lumbar motion segments
with a custom made BN filled with saline at internal fluid pressure of 0.3 or 0.6
MPa in terms of axial and rotational flexibilities of the L4-L5 motion segment.
Axial flexibility was quantified by the axial displacement resulting from an
axial compressive force of 400 N while the rotational flexibility by the range of
motions determined as the rotational angles in response to a pure moment of 6.0
Nm in flexion, extension, and right- and left-lateral bending directions. These
tests were performed successively on the motion segment in the following
conditions: intact, post nucleotomy, implanting BN with 0.3 MPa, and BN with 0.6
MPa. The nucleotomy was found to significantly increase both the axial and
rotational flexibilities while the implantation of the BN reduced the axial and
rotational flexibilities to those of the intact segment. The axial and rotational
flexibilities of the segment with the BN with 0.3 MPa were greater than those of
the segment with the BN with 0.6 MPa. (c) 2017 Orthopaedic Research Society.
Published by Wiley Periodicals, Inc. J Orthop Res 36:167-173, 2018.
PMID- 28513884
TI - Oxidized Quasi-Carbon Nitride Quantum Dots Inhibit Ice Growth.
AB - Antifreeze proteins (AFPs), a type of high-efficiency but expensive and often
unstable biological antifreeze, have stimulated substantial interest in the
search for synthetic mimics. However, only a few reported AFP mimics display
thermal hysteresis, and general criteria for the design of AFP mimics remain
unknown. Herein, oxidized quasi-carbon nitride quantum dots (OQCNs) are
synthesized through an up-scalable bottom-up approach. They exhibit thermal
hysteresis activity, an ice-crystal shaping effect, and activity on ice
recrystallization inhibition. In the cryopreservation of sheep red blood cells,
OQCNs improve cell recovery to more than twice that obtained by using a
commercial cryoprotectant (hydroxyethyl starch) without the addition of any
organic solvents. It is shown experimentally that OQCNs preferably bind onto the
ice-crystal surface, which leads to the inhibition of ice-crystal growth due to
the Kelvin effect. Further analysis reveals that the match of the distance
between two neighboring tertiary N atoms on OQCNs with the repeated spacing of O
atoms along the c-axis on the primary prism plane of ice lattice is critical for
OQCNs to bind preferentially on ice crystals. Here, the application of graphitic
carbon nitride derivatives for cryopreservation is reported for the first time.
PMID- 28513886
TI - Regulating Water-Reduction Kinetics in Cobalt Phosphide for Enhancing HER
Catalytic Activity in Alkaline Solution.
AB - Electrochemical water splitting to produce hydrogen renders a promising pathway
for renewable energy storage. Considering limited electrocatalysts have good
oxygen-evolution reaction (OER) catalytic activity in acid solution while
numerous economical materials show excellent OER catalytic performance in
alkaline solution, developing new strategies that enhance the alkaline hydrogen
evolution reaction (HER) catalytic activity of cost-effective catalysts is highly
desirable for achieving highly efficient overall water splitting. Herein, it is
demonstrated that synergistic regulation of water dissociation and optimization
of hydrogen adsorption free energy on electrocatalysts can significantly promote
alkaline HER catalysis. Using oxygen-incorporated Co2 P as an example, the
synergistic effect brings about 15-fold enhancement of alkaline HER activity.
Theory calculations confirm that the water dissociation free energy of Co2 P
decreases significantly after oxygen incorporation, and the hydrogen adsorption
free energy can also be optimized simultaneously. The finding suggests the
powerful effectiveness of synergetic regulation of water dissociation and
optimization of hydrogen adsorption free energy on electrocatalysts for alkaline
HER catalysis.
PMID- 28513887
TI - Geriatrics-for-Specialists Initiative: An Eleven-Specialty Collaboration to
Improve Care of Older Adults.
AB - In the early 1990s, visionary leaders at the American Geriatrics Society and The
John A. Hartford Foundation recognized that the marked and growing shortage of
geriatrics healthcare professionals would lead to a U.S. healthcare system ill
prepared to provide optimal care for the ever-increasing number of older
Americans. Led by the late Dennis W. Jahnigen, MD, they set forth a plan to
address this shortage by collaborating with surgical and related medical
specialists to create a series of programs to foster the highest quality care of
older adults. Their unique programmatic vision was that every physician, not just
geriatricians, would have basic knowledge and skills in geriatric care, because
geriatricians cannot and should not meet the need alone.
PMID- 28513889
TI - Mechanically induced bone formation is not sensitive to local osteocyte density
in rat vertebral cancellous bone.
AB - Osteocytes play an integral role in bone by sensing mechanical stimuli and
releasing signaling factors that direct bone formation. The importance of
osteocytes in mechanotransduction suggests that regions of bone tissue with
greater osteocyte populations are more responsive to mechanical stimuli. To
determine the effects of osteocyte population on bone functional adaptation we
applied mechanical loads to the 8th caudal vertebra of skeletally mature female
Sprague Dawley rats (6 months of age, n = 8 loaded, n = 8 sham controls). The
distribution of tissue stress/strain within cancellous bone was determined using
high-resolution finite element models, osteocyte distribution was determined
using nano-computed tomography, and locations of bone formation were determined
using three-dimensional images of fluorescent bone formation markers. Loading
increased bone formation (3D MS/BS 10.82 +/- 2.09% in loaded v. 3.17 +/- 2.05% in
sham control, mean +/- SD). Bone formation occurred at regions of cancellous bone
experiencing greater tissue stress/strain, however stress/strain was only a
modest predictor of bone formation; even at locations of greatest stress/strain
the probability of observing bone formation did not exceed 41%. The local
osteocyte population was not correlated with locations of new bone formation. The
findings support the idea that local tissue stress/strain influence the locations
of bone formation in cancellous bone, but suggest that the size of the osteocyte
population itself is not influential. We conclude that other aspects of
osteocytes such as osteocyte connectivity, lacunocanilicular nano-geometry,
and/or fluid pressure/shear distributions within the marrow space may be more
influential in regulating bone mechanotransduction than the number of osteocytes.
(c) 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J
Orthop Res 36:672-681, 2018.
PMID- 28513888
TI - Pain, Quality of Life, and Safety Outcomes of Kyphoplasty for Vertebral
Compression Fractures: Report of a Task Force of the American Society for Bone
and Mineral Research.
AB - The relative efficacy and harms of balloon kyphoplasty (BK) for treating
vertebral compression fractures (VCF) are uncertain. We searched multiple
electronic databases to March 2016 for randomized and quasi-randomized controlled
trials comparing BK with control treatment (nonsurgical management [NSM],
percutaneous vertebroplasty [PV], KIVA VCF treatment system [Benvenue Medical,
Inc., Santa Clara, CA, USA], vertebral body stenting, or other) in adults with
VCF. Outcomes included back pain, back disability, quality of life, new VCF, and
adverse events (AEs). One reviewer extracted data, a second checked accuracy, and
two rated risk of bias (ROB). Mean differences and 95% confidence intervals (CIs)
were calculated using inverse-variance models. Risk ratios of new VCF and AE were
calculated using Mantel-Haenszel models. Ten unique trials enrolled 1837
participants (age range, 61 to 76 years; 74% female), all rated as having high or
uncertain ROB. Versus NSM, BK was associated with greater reductions in pain,
back-related disability, and better quality of life (k = 1 trial) that appeared
to lessen over time, but were less than minimally clinically important
differences. Risk of new VCF at 3 and 12 months was not significantly different
(k = 2 trials). Risk of any AE was increased at 1 month (RR = 1.73; 95% CI, 1.36
to 2.21). There were no significant differences between BK and PV in back pain,
back disability, quality of life, risk of new VCF, or any AE (k = 1 to 3 trials).
Limitations included lack of a BK versus sham comparison, availability of only
one RCT of BK versus NSM, and lack of study blinding. Individuals with painful
VCF experienced symptomatic improvement compared with baseline with all
interventions. The clinical importance of the greater improvements with BK versus
NSM is unclear, may be due to placebo effect, and may not counterbalance short
term AE risks. Outcomes appeared similar between BK and other surgical
interventions. Well-conducted randomized trials comparing BK with sham would help
resolve remaining uncertainty about the relative benefits and harms of BK. (c)
2017 American Society for Bone and Mineral Research.
PMID- 28513890
TI - Risk of hospitalisation after early-revisit in the emergency department.
AB - AIM: Early-revisits are frequent in the paediatric emergency department (ED)
setting, but few data are available about early-revisited patients. The aim of
this study was to investigate the hospitalisation rate of a population of early
revisited patients and to detect if an early-revisited patient was at risk of a
more severe disease. METHODS: Between June 2014 and January 2015, we conducted a
retrospective cohort study, considering all patients presented to the ED of a
tertiary level children's hospital in Italy. We selected all patients who were
revisited within 72 h from the initial visit (study cohort), while all other
patients accessed in the same period were considered the control cohort. The two
cohorts were compared for age, gender, triage category, hospitalisation rate,
diagnosis at admission and hospital length of stay. RESULTS: In the study period,
we reviewed 10 750 visits, of which 430 (4%) were unplanned revisits for the same
chief complaint within 72 h from the initial visit. Hospitalisation rate of early
revisited patients was significantly higher compared to control patients (8.4 vs.
2.9%). Hospitalisation rate increases in parallel with the number of revisits,
but in many cases, it was not directly related to a worst triage category,
neither to a longer hospital length of stay. CONCLUSION: Early revisited patients
in the ED had a significantly higher risk of hospitalisation, but this risk was
only partially related to their clinical conditions.
PMID- 28513891
TI - Haematopoietic stem cell transplantation for severe combined immunodeficiency:
Long-term health outcomes and patient perspectives.
AB - AIM: To examine the long-term follow-up and health outcomes of patients who have
undergone haematopoietic stem cell transplant (HSCT) for severe combined
immunodeficiency (SCID). METHODS: Through a structured questionnaire, we examined
follow-up arrangements and long-term health outcomes in 22 children who have had
a successful HSCT for SCID during the period of 1984-2012 at the Sydney
Children's Hospital, Sydney, Australia. RESULTS: Most children considered
themselves healthy and 'cured' from SCID. Whilst many children enjoy relatively
good bio-social health outcomes, specific negative health outcomes and
absenteeism from school were perceived negatively. Two-thirds of children see
their general practitioner or specialist regularly; however, there did not appear
to be consistency with the nature of this follow-up. CONCLUSION: The findings
from our study highlight the complex bio-psychosocial health needs of post-HSCT
SCID children and encourage SCID centres to consider a multidisciplinary approach
to their follow-up. Further studies into the determinants of patients'
perceptions of their health are needed.
PMID- 28513892
TI - Assessment of nonarteritic anterior ischemic optic neuropathy with intravoxel
incoherent motion diffusion-weighted imaging using readout-segmented echo-planar
imaging, parallel imaging, and 2D navigator-based reacquisition.
AB - PURPOSE: To determine the feasibility of intravoxel incoherent motion (IVIM) for
characterizing perfusion properties and its potential diagnostic utility for
nonarteritic anterior ischemic optic neuropathy (NAION). IVIM diffusion-weighted
imaging is a promising technique that can measure perfusion and diffusion
characteristics simultaneously in a noninvasive manner. MATERIALS AND METHODS:
Orbital IVIM in a 3.0T scanner was performed on 33 patients with NAION and 15
controls using readout-segmented echo-planar imaging, parallel imaging, and 2D
navigator-based reacquisition (RESOLVE-IVIM). Both visual field (VF) and visual
acuity (VA) examinations were performed in 19 of the patients. The vascular
volume fraction (f), diffusion coefficient (D), and pseudodiffusion coefficient
(D*) were calculated for quantitative analysis. Additionally, correlation
analyses of IVIM parameters with visual function were also performed. RESULTS:
Affected optic nerves showed significantly lower f values than both unaffected
contralateral nerves of the patients and nerves of the controls (P < 0.0001), and
no significant difference for f was found between unaffected contralateral nerves
and nerves of the controls (P = 0.1602). In addition, D and D* values showed no
significant differences among the three groups (P = 0.0979, 0.0600, 0.6136 for D
and 0.1779, 0.6253, 0.4743 for D*). Correlation analysis only demonstrated
significant correlations between f values and the mean deviation of the visual
field (r = 0.576, P = 0.0051). CONCLUSION: RESOLVE-IVIM measurement may reflect
the perfusion abnormality and visual function impairment in NAION patients,
demonstrating its potential application for the diagnosis and clinical evaluation
of NAION. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson.
Imaging 2017;46:1760-1766.
PMID- 28513894
TI - The Dentoalveolar Prosthesis: A Novel Approach in the Reconstruction of Hard and
Soft Tissue Deficiencies.
AB - A clinical problem commonly encountered by the advanced restorative dentist is a
requirement to replace missing teeth and the supporting alveolus in areas
adjacent to healthy or manageable dentition. A potential solution could utilize a
dentoalveolar prosthesis fabricated on two or more implants in the edentulous
area. The implant substructure, or framework, may be cast, milled, or selectively
laser melted from a variety of metals. A superstructure, or ceramic overlay
incorporating a ceramic or composite resin gingival tissue component, is
constructed to fit over the implant substructure and luted to the substructure
with resin cement. This implant-supported fixed dental prosthesis identifies a
solution for the replacement of both teeth and supporting alveolar bone. It
restores comfort, function, and esthetics to the patient.
PMID- 28513893
TI - Relationship between iodine levels and papillary thyroid carcinoma: A systematic
review and meta-analysis.
AB - BACKGROUND: Iodine excess has been suggested as an exogenous risk factor of
papillary thyroid cancer (PTC). We performed a systematic review and meta
analysis to assess the relationship between iodine exposure measured in various
forms and PTC prevalence. METHODS: We searched MEDLINE, Embase, and the Cochrane
Library for case-control studies on iodine and PTC published up to December 2015.
Exposure to iodine was compared between PTC and control groups. RESULTS: From the
16 selected studies, the odds ratio (OR) for the overall effect size between high
iodine exposure and PTC risk was 1.418 (95% confidence interval [CI] 1.054
1.909). Based on 7 studies conducted in high iodinated regions, a positive
association between iodine exposure and PTC was observed (OR 2.200; 95% CI 1.389
3.483). CONCLUSION: This study demonstrated a higher exposure to iodine in
patients with PTC compared with controls, especially for patients from high
iodinated regions.
PMID- 28513895
TI - One-year quality of life and functional outcomes of transoral robotic surgery for
carcinoma of unknown primary.
AB - BACKGROUND: The purpose of this study was to assess the quality of life (QOL)
outcomes in patients who underwent transoral robotic surgery (TORS) for carcinoma
of unknown primary (CUP). METHODS: Twenty-nine patients with CUP were
administered the Head and Neck Cancer Inventory (HNCI) prospectively to evaluate
QOL preoperatively and postoperatively. RESULTS: There was statistically and
clinically significant deterioration in 2 of 4 domains (eating and social
disruption) in the immediate aftermath of TORS. There was statistically and
clinically meaningful deterioration in all 4 domains at 3 months relative to
baseline, and there remained statistically and clinically meaningful
deterioration in 2 of 4 domains at 6 months compared to baseline. These 2 domains
remained statistically and clinically worse than baseline at 12 months. Speech
and aesthetics domain scores were comparable at baseline and 12 months.
CONCLUSION: Patients reported difficulties with eating and social disruption over
the course of 1 year, but problems with speech and appearance abated.
PMID- 28513896
TI - Management and outcomes of patients with recurrent neuroendocrine liver
metastasis after curative surgery: An international multi-institutional analysis.
AB - OBJECTIVE: We sought to characterize the treatment, as well as define the long
term outcomes, of patients with recurrent neuroendocrine liver metastasis (NELM).
METHODS: Between 1990 and 2014, 322 patients undergoing curative intent liver
surgery for NELM were identified from a multi-institutional database. Recurrences
were classified as intrahepatic, extrahepatic, and both intra- and extra-hepatic.
RESULTS: Overall, median, 1-, 5-, 10-year DFS were 3.1 years, 75.5%, 40.4%, and
32.1%, respectively. After curative intent liver surgery, 209 patients (64.9%)
recurred within a median follow-up of 4.5 years, while 113 (35.1%) patients were
alive without disease with a follow-up time >=3 years. The site of recurrence was
intrahepatic only (n = 111, 65.7%), extrahepatic only (n = 19, 11.2%), or intra-
and extra-hepatic (n = 39, 23.1%). Compared with intrahepatic only recurrence,
extrahepatic only, and combined intra- and extra-hepatic recurrence were
associated with a worse long-term outcome (10-year OS: intrahepatic only, 42.5%,
95%CI, 24.9-59.0 vs extrahepatic only, 0% and combined intra- and extra-hepatic,
21.5%, 95%CI, 5.3-44.0) (P < 0.001). Most patients were treated with repeat
surgery (n = 49, 36.6%), while 34 (23.5%) patients received a somatostatin
analogue, 27 (18.6%) systemic cytotoxic chemotherapy, and 27 (21.4%) patients had
intra-arterial therapy. Ten-year OS among patients who underwent repeat surgery
or intra-arterial treatments was 60.3% (95%CI, 34.1-78.8) and 52.0% (95%CI, 30.6
69.9), respectively. Patients who received somatostatin analogues (45.9% 95%CI,
22.3-66.9) or systemic chemotherapy (0%) had a shorter long-term survival (P =
0.001). CONCLUSION: Recurrence after surgery for NELM occurred among half of
patients. Repeat liver resection for recurrence may offer a reasonable 5-year
survival benefit.
PMID- 28513897
TI - Quality and Survival of Direct Light-Activated Composite Resin Restorations in
Posterior Teeth: A 5- to 20-Year Retrospective Longitudinal Study.
AB - PURPOSE: To analyze the clinical success of direct light-activated composite
resin restorations in posterior teeth. The quality of the margins and occlusal
surfaces were evaluated, as well as their survival, according to their extensions
and locations. The clinical performance of posterior composite resin restorations
with different compositions were compared. All restorations were performed by the
first author in his private practice, in a 5- to 20-year period. MATERIALS AND
METHODS: Several types of composite resins, provided by different manufacturers,
were placed in posterior teeth, after isolation with rubber dams. To be included
in the study, the restorations had to have been in function for at least 5 years
and had to have been placed between October 1993 and October 2008 by the first
author. The established failure criteria were: tooth and/or restoration fracture,
secondary caries, endodontic treatment, or tooth loss. Included patients must
have been treated in the first author's office for at least 7 years and still in
the practice through 2013; all patients had complete dental arches. Patients with
removable dental prostheses or disabilities, who had moved, or who had died were
excluded. Of 210 patients who fulfilled the inclusion criteria, 138 randomly
selected subjects were clinically examined between November 2013 and April 2014.
Of these 138 patients, 61 had received 105 direct-light-activated composite resin
restorations in posterior teeth, which met the inclusion criteria. Twenty-nine
patients (47.5%) underwent annual maintenance therapy. The patient-based data
collected from clinical exams and personal records were recorded on a specially
designed form. Age, gender, period of clinical attendance, tooth preparation,
location, size, quality and longevity of the restorations, restorative materials,
adhesive systems, parafunctional habits, secondary caries, and maintenance
therapy were the variables evaluated. Authors were blinded to the clinical
assessments. Cohen's Kappa coefficient of the quality analysis of the margins and
occlusal surfaces of the restorations ranged from 0.78 to 1. Data processing was
performed using Epidat software, v3.1, developed by the Conselleria de Sanidade
de la Xunta de Galicia with the support of PAHO-WHO and SPSS software v13.0. If
the number of complete values was too small, a Kaplan-Meier curve could not be
used. Therefore the Fisher's exact test, Chi-square test, Kruskal-Wallis test,
and Mann-Whitney non-parametric test were indicated to analyze significant
differences. RESULTS: At the time of the examinations, 103 (98%) restorations
were in function, and 98 (95.1%) were rated as clinically successful. Two
restorations failed (2%). The observed mean survival time of restorations that
remained functional was 11 years and 7 months. CONCLUSIONS: In the present
report, direct light-activated composite resin restorations in posterior teeth
showed a high clinical success rate and long-term mean survival time. These
composite resins might be considered the material of choice to restore medium,
extended, and in some clinical situations, large preparations in posterior teeth.
PMID- 28513898
TI - Synthesis of BODIPY-Labeled Cholesterylated Glycopeptides by Tandem Click
Chemistry for Glycocalyxification of Giant Unilamellar Vesicles (GUVs).
AB - The glycocalyx cover membrane surfaces of all living cells. These complex
architectures render their interaction mechanisms on the membrane surface
difficult to study. Artificial cell-sized membranes with selected and defined
glycosylation patterns may serve as a minimalistic approach to systematically
study cell surface glycan interactions. The development of a facile general
synthetic procedure for the synthesis of BODIPY-labeled cholesterylated
glycopeptides, which can coat cell-size giant unilamellar vesicles (GUVs), is
described. These peptide constructs were synthesized by: 1) solid-phase peptide
synthesis (SPPS) using cholesterylated Fmoc-amino acids (Fmoc=9
fluorenylmethoxycarbonyl) followed by tandem click reactions, 2) attachment of a
BODIPY-bicyclononyne (BCN) (prepared by Mitsunobu chemistry via novel aryl BCN
ethers) in the absence of a catalyst, and 3) glycosylation by means of copper(I)
catalyzed click reaction of an azidoglycan. Seven different GUV-glycoforms were
prepared and four of these were evaluated with their corresponding four specific
anti-glycan binding lectins.
PMID- 28513900
TI - Unraveling the Coulombic Forces in Electronically Decoupled Bichromophoric
Systems during Two Successive Electron Transfers.
AB - Coulombic forces are vital in modulating the electron transfer dynamics in both
synthetic and biological polychromophoric assemblies, yet quantitative studies of
the impact of such forces are rare, as it is difficult to disentangle
electrostatic forces from simple electronic coupling. To address this problem,
the impact of Coulombic interactions in the successive removal of two electrons
from a model set of spirobifluorenes, where the interchromophoric electronic
coupling is nonexistent, is quantitatively assessed. By systematically varying
the separation of the bifluorene moieties using model compounds, ion pairing, and
solvation, these interactions, with energies up to about 0.4 V, are absent at
distances greater than about 9 A. These findings can be (quantitatively) applied
for the design of polychromophoric assemblies, whereby the redox properties of
donors and/or acceptors can be tuned by judicious positioning of the charged
groups to control the electron-transfer dynamics.
PMID- 28513899
TI - Surgical strategies and novel therapies for locally advanced pancreatic cancer.
AB - Many patients with pancreatic cancer are not candidates for surgical resection
due to involvement of critical mesenteric vascular structures. We compare and
contrast the commonly used classification systems for borderline resectable and
locally advanced pancreatic cancer. We describe the current strategies in
managing venous and arterial involvement, as well as the role of neoadjuvant
chemotherapy and chemoradiation, before explanding on a novel clinical trial in
this patient population.
PMID- 28513901
TI - Transcriptomic profiling reveals disordered regulation of surfactant homeostasis
in neonatal cloned bovines with collapsed lungs and respiratory distress.
AB - Respiratory distress is a major cause of mortality in cloned neonatal animals,
but its pathogenesis remains poorly understood. Here, we used necropsy and
histology procedures to evaluate the lungs of cloned neonatal bovines dying of
respiratory distress, finding incomplete lung dilation, alveolar collapse, and
thickened alveolar walls. Comparison of the transcriptomes between collapsed
lungs of cloned bovines and their normal counterparts revealed 1373
differentially expressed genes in collapsed lungs (p < 0.05, fold change >1.5 or
<1.5-1 ), many of which were associated with surfactant biosynthesis, secretion,
transport, recycling, and degradation. ERK/MAPK and Notch signaling pathways were
among the canonical pathways relevant to surfactant homeostasis. Expression of
the genes encoding Surfactant protein B (SPB) and Surfactant protein C (SPC)
which control surfactant lipid packing, spreading, and stability-were
significantly lower in collapsed lungs of cloned neonates at the transcript (p <
0.01) and protein levels (p < 0.05) relative to that in normal lungs. Thus, our
results provide an initial view into the changes in gene expression in cloned
newborns with lung collapse and respiratory distress, and present a valuable
resource for developing novel preventive or therapeutic strategies to reduce the
mortality rate of cloned animals and to improve the efficiency of somatic cell
nuclear transfer technology.
PMID- 28513902
TI - Prospective analysis of radiation oncology image and plan-driven peer review for
head and neck cancer.
AB - BACKGROUND: Departmental "chart rounds" is an established form of review in
radiation oncology, however, evidence is lacking that identifies links between
features of a more subspecialized disease site-specific review and the likelihood
and characteristics of recommendations made. We prospectively analyzed our head
and neck group's review process to identify associations that could guide future
practice. METHODS: Our group reviewed proposed management and treatment volumes
for radiation simulated patients on a weekly basis, and we collected data
encompassing recommendations made by individuals or group consensus. RESULTS:
Changes in management, prescribed dose, radiation fractionation, clinical target
volumes, or target contours were suggested in 85 of 182 cases. The most
frequently recommended changes were adjustment of regions treated or target
contours, and an inverse correlation was observed between the number of attending
physicians present and specific changes suggested to the gross tumor volume
(GTV). CONCLUSION: We find that site-specific head and neck peer review results
in frequent recommendations largely independent of the type of case reviewed.
PMID- 28513911
TI - Sperm capacitation pretreatment positively impacts bovine intracytoplasmic sperm
injection.
AB - The efficiency of intracytoplasmic sperm injection (ICSI) in bovines is low
compared to other species due in part to inadequate egg activation and sperm
nucleus decondensation after injection. We hypothesized that this low efficiency
is due to the lack of complete sperm capacitation, so we evaluated the effects of
isobutylmethylxanthine (IBMX) and methyl-beta-cyclodextrin (MbetaCD) on bovine
sperm capacitation and on the preimplantation developmental potential of bovine
embryos generated by ICSI. Treatment with IBMX and MbetaCD decreased sperm
viability (between 13-30%); nevertheless, 0.4 mM IBMX and 1 mM MbetaCD increased
(p < 0.05) capacitation metrics-that is, acrosome exocytosis, intracellular
calcium level, plasma membrane fluidity, and tyrosine phosphorylation-compared to
the control. After ICSI, embryos injected with IBMX- and MbetaCD-treated sperm
showed similar cleavage to the untreated group (range 82-88%). Pronucleus
formation rate was higher with MbetaCD-pretreatment (54%) compared to the control
group (25%), and blastocyst rate was significantly improved with MbetaCD
pretreatment (24%) compared to the IBMX (18%) and control (17%) groups.
Importantly, embryo quality-as assessed by the total number of cells, cell
allocation, and apoptotic cell index-was not affected by the sperm treatments. In
conclusion, MbetaCD pretreatment of sperm improved the efficiency of blastocyst
production in bovine ICSI.
PMID- 28513913
TI - Determination of role of ceruloplasmin in oral potentially malignant disorders
and oral malignancy-A cross-sectional study.
AB - OBJECTIVES: In the process of carcinogenesis, lipid peroxidation and increased
oxidative stress lead to changes in certain antioxidants. This study was aimed to
assess and co-relate serum levels of ceruloplasmin in oral premalignancies and
oral cancer so as to gauge its possible association with the process of
carcinogenesis and to determine its role as tumor marker. MATERIAL AND METHODS:
The study population comprised of 300 participants, equally divided into six
study groups, that is, oral submucous fibrosis (OSMF), oral leukoplakia (OL),
nicotina stomatitis (NS), oral malignancy (OM), controls (C), and healthy
controls (HC); 5 ml of blood was collected from ante cubital vein from each
participant. The serum was analyzed for ceruloplasmin levels using ERBA CHEM 5
PLUS semiautomated chemistry analyzer and diagnostic kit by turbidimetric
immunoassay. RESULTS: There were total 242 males and 58 females, who were between
18 and 82 years of age, with a mean of 45.31 +/- 13.97 years. The serum
ceruloplasmin levels were significantly increased in OM, OSMF, OL, and NS groups
as compared to C and HC groups (p < .001). No statistically significant
difference was found in intragroup analysis of the disease groups (p > .05).
CONCLUSION: Serum ceruloplasmin can be used as diagnostic marker for oral
premalignant and malignant lesions.
PMID- 28513914
TI - Competition versus Cooperation in Catalytic Hydrogelators for anti-Selective
Mannich Reaction.
AB - Chemical systems find similarities in different sociological and biological
processes, in which the entities compete or cooperate for a favorable outcome.
The structural and functional adaptations leading to emergent properties,
especially in catalysis, are based on factors such as abundance of substrates,
stability of the transition state, and structural/functional attributes of
catalysts. Proline and acid groups appended to catalytic fibers of two self
sorting hydrogelators compete for the Mannich reaction between aniline,
benzaldehyde, and cyclohexanone to give low overall selectivity (anti/syn 77:23).
In a sol-gel system of the same molecules, on the other hand, the soluble acid
appended molecules tend to cooperate with the fibers of proline-appended catalyst
to give improved selectivity (anti/syn 95:5). The available options for the
catalytic molecules are to carry out the reaction independently or in
cooperation. However, these options are chosen based on the efficiency,
selectivity, and mobility of catalysts as a result of their abilities to self
assemble.
PMID- 28513912
TI - Improving theranostics in pancreatic cancer.
AB - BACKGROUND: Pancreatic cancer is the fourth most deadly cancer in the United
States, and is expected to be the second most deadly by 2030. The major
difficulty in treating pancreatic cancer is the late onset of symptoms.
Generally, patients show metastatic disease by the time of diagnosis, with a
survival rate of 5% beyond 5 years. In patients without metastatic disease,
surgical resection increases 5 year survival rate to 25%. The remaining 75%
succumb to undetected metastases. Clearly, improvements to both detection,
surgical intervention, and therapeutic strategies will be needed to improve
patient outcome in pancreatic cancer. METHODS: Recent literature has been
surveyed and atomic models of new therapeutic approaches were generated. RESULTS
AND CONCLUSIONS: Here, we focus on the recent progress employing monoclonal
antibodies (mAbs) to target pancreatic cancer associated markers, and more
specifically on recent chemical and protein engineering efforts to improve the
homogeneity, stability, and administration of mAbs to precisely deliver imaging
agents and cytotoxins to sites of disease.
PMID- 28513915
TI - Impact of "a" determinant mutations on detection of hepatitis B surface antigen
(HBsAg) in HBV strains from Chinese patients with occult hepatitis B.
AB - This study was designed to detect mutations that occur within the "a" determinant
in the S gene of the hepatitis B virus (HBV) in patients with occult hepatitis B
(OHB), and to analyze the influence of these mutations on expression and
reactivity of the hepatitis B surface antigen (HBsAg). Twenty-three certified OHB
samples were compared to 32 HBsAg positive samples from patients with chronic
hepatitis B. The median HBV DNA levels in the OHB group were significantly lower
than those in the control group (P < 0.0001). Mutations within the "a"
determinant were analyzed by gene amplification and sequencing. This revealed
mixed infections in which clones within a sample displayed either different
mutations or mutations in association with clones that exhibited wild type amino
acid patterns. Sequencing analysis also showed a significant difference between
the proportions of amino acid mutations observed in the OHB and control groups.
Seven recombinant S (rS) proteins with corresponding OHB mutations and three wild
type alleles were expressed and purified in the Pichia pastoris expression system
to preserve conformational attributes, and their reactivity analyzed using six
commercial HBsAg assays. The OHB sera were HBsAg nonreactive while the rS
proteins with corresponding OHB mutations were universally reactive. Thus, we
postulate that the reduced binding affinity between mutated HBsAg and its
antibody may not be as important in defining OHB as is the effect of specific
mutations in the preS/S region of the genome that affect the synthesis and
secretion of the S protein and/or the virion.
PMID- 28513917
TI - Fragment Screening against the EthR-DNA Interaction by Native Mass Spectrometry.
AB - Native nanoelectrospray ionization mass spectrometry is an underutilized
technique for fragment screening. In this study, the first demonstration is
provided of the use of native mass spectrometry for screening fragments against a
protein-DNA interaction. EthR is a transcriptional repressor of EthA expression
in Mycobacterium tuberculosis (Mtb) that reduces the efficacy of ethionamide, a
second-line antitubercular drug used to combat multidrug-resistant Mtb strains. A
small-scale fragment screening campaign was conducted against the EthR-DNA
interaction using native mass spectrometry, and the results were compared with
those from differential scanning fluorimetry, a commonly used primary screening
technique. Hits were validated by surface plasmon resonance and X-ray
crystallography. The screening campaign identified two new fragments that disrupt
the EthR-DNA interaction in vitro (IC50 =460-610 MUm) and bind to the hydrophobic
channel of the EthR dimer.
PMID- 28513916
TI - Global forest carbon uptake due to nitrogen and phosphorus deposition from 1850
to 2100.
AB - Spatial patterns and temporal trends of nitrogen (N) and phosphorus (P)
deposition are important for quantifying their impact on forest carbon (C)
uptake. In a first step, we modeled historical and future change in the global
distributions of the atmospheric deposition of N and P from the dry and wet
deposition of aerosols and gases containing N and P. Future projections were
compared between two scenarios with contrasting aerosol emissions. Modeled fields
of N and P deposition and P concentration were evaluated using globally
distributed in situ measurements. N deposition peaked around 1990 in European
forests and around 2010 in East Asian forests, and both increased sevenfold
relative to 1850. P deposition peaked around 2010 in South Asian forests and
increased 3.5-fold relative to 1850. In a second step, we estimated the change in
C storage in forests due to the fertilization by deposited N and P (?Cnu dep ),
based on the retention of deposited nutrients, their allocation within plants,
and C:N and C:P stoichiometry. ?Cnu dep for 1997-2013 was estimated to be 0.27 +/
0.13 Pg C year-1 from N and 0.054 +/- 0.10 Pg C year-1 from P, contributing 9%
and 2% of the terrestrial C sink, respectively. Sensitivity tests show that
uncertainty of ?Cnu dep was larger from P than from N, mainly due to uncertainty
in the fraction of deposited P that is fixed by soil. ?CPdep was exceeded by
?CNdep over 1960-2007 in a large area of East Asian and West European forests due
to a faster growth in N deposition than P. Our results suggest a significant
contribution of anthropogenic P deposition to C storage, and additional sources
of N are needed to support C storage by P in some Asian tropical forests where
the deposition rate increased even faster for P than for N.
PMID- 28513918
TI - Cyclic Polysiloxanes with Linked Cyclotetrasiloxane Subunits.
AB - Cyclic polymers are an important class of macromolecules, but the structural
diversity of the backbone is limited. Herein we report the use of the Piers
Rubinsztajn reaction for the one-step synthesis of cyclic polysiloxanes with
novel structural features. Specifically, the B(C6 F5 )3 -catalyzed coupling of
various organic tris(dimethylsiloxy)silane and trialkoxysilane compounds
generated a series of cyclic polysiloxanes with cyclotetrasiloxane subunits. The
thiolated cyclic polymers were also shown to be effective in directing the
circular assembly gold nanoparticles. The presence of constrained rings in the
backbone is unprecedented and may offer opportunities for novel applications of
these cyclic polymers.
PMID- 28513919
TI - Functional status and mortality prediction in community-acquired pneumonia.
AB - BACKGROUND AND OBJECTIVE: Poor functional status (FS) has been suggested as a
poor prognostic factor in both pneumonia and severe pneumonia in elderly
patients. However, it is still unclear whether FS is associated with outcomes and
improves survival prediction in community-acquired pneumonia (CAP) in the general
population. METHODS: Data on hospitalized patients with CAP and FS, assessed by
the Eastern Cooperative Oncology Group (ECOG) scale were prospectively collected
between January 2008 and December 2012. The independent association of FS with 30
day mortality in CAP patients was evaluated using multivariable logistic
regression. Improvement in mortality prediction when FS was added to the CRB-65
(confusion, respiratory rate, blood pressure and age 65) score was evaluated for
discrimination, reclassification and calibration. RESULTS: The 30-day mortality
of study participants (n = 1526) was 10%. Mortality significantly increased with
higher ECOG score (P for trend <0.001). In multivariable analysis, ECOG >=3 was
strongly associated with 30-day mortality (adjusted OR: 5.70; 95% CI: 3.82-8.50).
Adding ECOG >=3 significantly improved the discriminatory power of CRB-65.
Reclassification indices also confirmed the improvement in discrimination ability
when FS was combined with the CRB-65, with a categorized net reclassification
index (NRI) of 0.561 (0.437-0.686), a continuous NRI of 0.858 (0.696-1.019) and a
relative integrated discrimination improvement in the discrimination slope of
139.8 % (110.8-154.6). CONCLUSION: FS predicted 30-day mortality and improved
discrimination and reclassification in consecutive CAP patients. Assessment of
premorbid FS should be considered in mortality prediction in patients with CAP.
PMID- 28513920
TI - Moisture-induced greening of the South Asia over the past three decades.
AB - South Asia experienced a weakening of summer monsoon circulation in the past
several decades, resulting in rainfall decline in wet regions. In comparison with
other tropical ecosystems, quantitative assessments of the extent and triggers of
vegetation change are lacking in assessing climate-change impacts over South Asia
dominated by crops. Here, we use satellite-based Normalized Difference Vegetation
Index (NDVI) to quantify spatial-temporal changes in vegetation greenness, and
find a widespread annual greening trend that stands in contrast to the weakening
of summer monsoon circulation particularly over the last decade. We further show
that moisture supply is the primary factor limiting vegetation activity during
dry season or in dry region, and cloud cover or temperature would become
increasingly important in wet region. Enhanced moisture conditions over dry
region, coinciding with the decline in monsoon, are mainly responsible for the
widespread greening trend. This result thereby cautions the use of a unified
monsoon index to predict South Asia's vegetation dynamics. Current climate-carbon
models in general correctly reproduce the dominant control of moisture in the
temporal characteristics of vegetation productivity. But the model ensemble
cannot exactly reproduce the spatial pattern of satellite-based vegetation change
mainly because of biases in climate simulations. The moisture-induced greening
over South Asia, which is likely to persist into the wetter future, has
significant implications for regional carbon cycling and maintaining food
security.
PMID- 28513921
TI - Chitin-induced and CHITIN ELICITOR RECEPTOR KINASE1 (CERK1) phosphorylation
dependent endocytosis of Arabidopsis thaliana LYSIN MOTIF-CONTAINING RECEPTOR
LIKE KINASE5 (LYK5).
AB - To detect potential pathogens, plants perceive the fungal polysaccharide chitin
through receptor complexes containing lysin motif receptor-like kinases (LysM
RLKs). To investigate the ligand-induced spatial dynamics of chitin receptor
components, we studied the subcellular behaviour of two Arabidopsis thaliana LysM
RLKs involved in chitin signalling, CHITIN ELICITOR RECEPTOR KINASE1 (CERK1) and
LYSIN MOTIF-CONTAINING RECEPTOR-LIKE KINASE5. We performed standard and
quantitative confocal laser scanning microscopy on stably transformed A. thaliana
plants expressing fluorescently tagged CERK1 and LYK5 from their native
promoters. Microscopy approaches were complemented by biochemical analyses in
plants and in vitro. Both CERK1 and LYK5 localized to the plasma membrane and
showed constitutive endomembrane trafficking. After chitin treatment, however,
CERK1 remained at the plasma membrane while LYK5 relocalized into mobile
intracellular vesicles. Detailed analyses revealed that chitin perception
transiently induced the internalization of LYK5 into late endocytic compartments.
Plants that lacked CERK1 or expressed an enzymatically inactive CERK1 variant did
not exhibit chitin-induced endocytosis of LYK5. CERK1 could phosphorylate LYK5 in
vitro and chitin treatment induced CERK1-dependent phosphorylation of LYK5 in
planta. Our results suggest that chitin-induced phosphorylation by CERK1 triggers
LYK5 internalization. Thus, our work identifies phosphorylation as a key
regulatory step in endocytosis of plant RLKs and also provides evidence for
receptor complex dissociation after ligand perception.
PMID- 28513922
TI - Impact of sampling interval in training data acquisition on intrafractional
predictive accuracy of indirect dynamic tumor-tracking radiotherapy.
AB - PURPOSE: To explore the effect of sampling interval of training data acquisition
on the intrafractional prediction error of surrogate signal-based dynamic tumor
tracking using a gimbal-mounted linac. MATERIALS AND METHODS: Twenty pairs of
respiratory motions were acquired from 20 patients (ten lung, five liver, and
five pancreatic cancer patients) who underwent dynamic tumor-tracking with the
Vero4DRT. First, respiratory motions were acquired as training data for an
initial construction of the prediction model before the irradiation. Next,
additional respiratory motions were acquired for an update of the prediction
model due to the change of the respiratory pattern during the irradiation. The
time elapsed prior to the second acquisition of the respiratory motion was 12.6
+/- 3.1 min. A four-axis moving phantom reproduced patients' three dimensional
(3D) target motions and one dimensional surrogate motions. To predict the future
internal target motion from the external surrogate motion, prediction models were
constructed by minimizing residual prediction errors for training data acquired
at 80 and 320 ms sampling intervals for 20 s, and at 500, 1,000, and 2,000 ms
sampling intervals for 60 s using orthogonal kV x-ray imaging systems. The
accuracies of prediction models trained with various sampling intervals were
estimated based on training data with each sampling interval during the training
process. The intrafractional prediction errors for various prediction models were
then calculated on intrafractional monitoring images taken for 30 s at the
constant sampling interval of a 500 ms fairly to evaluate the prediction accuracy
for the same motion pattern. In addition, the first respiratory motion was used
for the training and the second respiratory motion was used for the evaluation of
the intrafractional prediction errors for the changed respiratory motion to
evaluate the robustness of the prediction models. RESULTS: The training error of
the prediction model was 1.7 +/- 0.7 mm in 3D for all sampling intervals. The
intrafractional prediction error for the same motion pattern was 1.9 +/- 0.7 mm
in 3D for an 80 ms sampling interval, which increased larger than 1 mm in 10.0%
of prediction models trained at a 2,000 ms sampling interval with a significant
difference (P < 0.01) and up to 2.5% for the other sampling intervals without a
significant difference (P > 0.05). The intrafractional prediction error for the
changed respiratory motion pattern increased to 5.1 +/- 2.4 mm in 3D for an 80 ms
sampling interval; however, there was not a significant difference in the
robustness of the prediction model between the 80 ms sampling interval and other
sampling intervals (P > 0.05). CONCLUSIONS: Although the training error of the
prediction model was consistent for the all sampling intervals, the prediction
model using the larger sampling interval of the 2,000 ms increased the
intrafractional prediction error for the same motion pattern. The realistic
accuracy of the prediction model was difficult to estimate using the larger
sampling interval during the training process. It is recommended to construct the
prediction model at sampling interval <= 1,000 ms and to reconstruct the model
during treatment.
PMID- 28513923
TI - Histological variability and consequences in chronic bird-related
hypersensitivity pneumonitis.
AB - BACKGROUND AND OBJECTIVE: Lobar and temporal histological variability in chronic
bird-related hypersensitivity pneumonitis (BRHP) has not been clearly elucidated.
This study was designed to evaluate the spatio-temporal histopathological
variability in chronic BRHP. METHODS: Fifty-two patients with chronic BRHP who
underwent a surgical lung biopsy (SLB) between 1992 and 2008 were evaluated. The
histopathological characteristics of the lung biopsy specimens were classified by
the 2002 American Thoracic Society/European Respiratory Society (ATS/ERS)
consensus classification of idiopathic interstitial pneumonias (IIPs). Autopsy
specimens from seven patients were also evaluated to examine the serial changes
from SLB to autopsy. RESULTS: In a study of lobar histological variability based
on the findings of SLB, 7 patients were diagnosed with cellular nonspecific
interstitial pneumonia (NSIP) pattern, 16 with fibrotic NSIP pattern, 20 with
fibrotic NSIP pattern and usual interstitial pneumonia (UIP) (discordant UIP)
pattern and 9 with UIP (concordant UIP) pattern. In a study of sequential
changes, specimens of SLBs with fibrotic NSIP pattern changed to a
bronchiolocentric interstitial pneumonia (BIP) pattern or UIP pattern.
CONCLUSION: Interlobar and intralobar histological variability is present in
chronic BRHP. In several patients with chronic BRHP, a fibrotic NSIP pattern may
be an early lesion that progresses to a UIP pattern.
PMID- 28513924
TI - Glycan Fingerprinting via Cold-Ion Infrared Spectroscopy.
AB - The diversity of stereochemical isomers present in glycans and glycoconjugates
poses a formidable challenge for comprehensive structural analysis. Typically,
sophisticated mass spectrometry (MS)-based techniques are used in combination
with chromatography or ion-mobility separation. However, coexisting structurally
similar isomers often render an unambiguous identification impossible. Other
powerful techniques such as gas-phase infrared (IR) spectroscopy have been
limited to smaller glycans, since conformational flexibility and thermal
activation during the measurement result in poor spectral resolution. This
limitation can be overcome by using cold-ion spectroscopy. The vibrational
fingerprints of cold oligosaccharide ions exhibit a wealth of well-resolved
absorption features that are diagnostic for minute structural variations. The
unprecedented resolution of cold-ion spectroscopy coupled with tandem MS may
render this the key technology to unravel complex glycomes.
PMID- 28513937
TI - John R. Cameron.
PMID- 28513947
TI - Response to "Comment on 'Update of AAPM Task Group No. 43 Report: A revised AAPM
protocol for brachytherapy dose calculations' " [Med. Phys. 31, 633-674 (2004)].
PMID- 28513968
TI - The views of ethics committee members and medical researchers on the return of
individual research results and incidental findings, ownership issues and benefit
sharing in biobanking research in a South Indian city.
AB - The return of individual research results and incidental findings from biobanking
research is a much debated ethical issue globally but has extensive relevance in
India where the burden of out of pocket health care expenses is high for the
majority. The views of 21 ethics committee (EC) members and 22 researchers from
Bengaluru, India, concerning the ethics of biobanking research were sought
through in-depth interviews using an unfolding case vignette with probes. A
shared view among most was that individual research results which are
'actionable' or have 'clinical significance' should be returned to the sample
contributors through their treating physicians. This was seen as an ethical
obligation and a moral duty on the side of the researcher to "give back" to the
person who contributed to the research. The challenges foreseen were that of
resources, both financial and personnel, for the time and counseling needed to
accompany the disclosure of results. Perceptions of 'ownership' appear to
influence the concept of benefit sharing. While benefit sharing in financial
terms was considered ethically challenging, certain researchers and ethics
committee members made a case for "two way altruism" where the researcher in
return for the altruistic 'valuable contribution', shares with the contributor/
community, benefits of the research which could include research findings,
improved patient care, and more affordable access to the new diagnostic tests or
products arising from the research. This defines the emerging ethic of "giving
back" which goes beyond individual rights and ensures reciprocity and
distributive justice.
PMID- 28513969
TI - Effect of Steady-State Faldaprevir on Pharmacokinetics of Atorvastatin or
Rosuvastatin in Healthy Volunteers: A Prospective Open-Label, Fixed-Sequence
Crossover Study.
AB - Faldaprevir (FDV) is a potent, orally administered inhibitor of hepatitis C virus
protease. It inhibits multiple cytochrome P-450 enzymes and multiple membrane
transporters. The objective of this study was to evaluate the effect of steady
state faldaprevir on the pharmacokinetics (PK) of a single dose of atorvastatin
or rosuvastatin. In this single-center, open-label, fixed-sequence crossover
study, 33 healthy adult male and female volunteers were given either atorvastatin
10 mg (n = 16) or rosuvastatin 10 mg (n = 17) on day 1. Subjects subsequently
received 240 mg twice daily of faldaprevir (loading dose) on day 5, followed by
240 mg faldaprevir once daily from day 6 to day 10, with an additional single
dose of atorvastatin (10 mg) or rosuvastatin (10 mg) given on day 10. PK samples
for the statins were collected on days 1-3 and days 10-12. Concomitant
administration with faldaprevir led to approximately 9-fold and 34-fold increases
in AUC0-infinity and Cmax , respectively, of atorvastatin and approximately 15
fold and 33-fold increases in AUC0-infinity and Cmax , respectively, of
rosuvastatin, compared with the statins given alone. Exposure to the major
metabolites (ortho-hydroxyatorvastatin and N-desmethylrosuvastatin) was increased
to a similar magnitude as that of the parent compounds. The marked drug-drug
interaction observed is most likely related to the inhibitory effects of
faldaprevir on transporters, particularly hepatic uptake transporters such as
OTAP1B1 and OATP1B3. Given the significant increase in exposure to statins in
healthy volunteers, coadministration of faldaprevir with statins should be
avoided.
PMID- 28513970
TI - Cytomegalovirus infection and atherosclerosis risk: A meta-analysis.
AB - Human cytomegalovirus (HCMV) infection is an important risk factor for
atherosclerosis (AS). Numerous studies have been conducted to analyze the
association between HCMV infection and risk of AS, but no clear consensus has
been reached. So the objective of this paper was aimed to demonstrate the
relationship between HCMV and AS by doing a meta-analysis. Relative literature
was searched through the electronic databases PubMed, Embase, and CNKI. Data were
accurately assessed and analyzed independently by two investigators. Ultimately,
the 30 studies, involving 3328 cases and 2090 controls were included in our meta
analysis. The positive ratio of HCMV IgG, IgM, DNA and pp65 were, respectively,
63.26% (923/1459), 25.46% (69/271), 33.69% (381/1131), and 50.32% (158/314) in
case patients. Meanwhile the positive ratio of HCMV IgG, IgM, DNA, and pp65 were,
respectively, 52.12% (541/1038), 1.55% (3/194), 13.72% (79/576), and 12.26%
(28/229) in control subjects. The positive ratio of HCMV infection was higher in
atherosclerosis group than that in non-atherosclerosis group. Especially in Asian
group, calculated odds ratios for the presence of HCMV infection in IgG-based
HCMV tests, IgM-based tests, PCR-based tests, and pp65-based tests, expressed as
OR (95% confidence intervals, 95%CI), were 3.07(95%CI 2.09-4.51), 8.92(95%CI 3.17
25.11), 6.75 (95%CI 3.50-13.02), and 5.72(95%CI 1.51-21.58), respectively. The
meta-analysis results showed that HCMV infection is significant connected with an
increased risk for AS.
PMID- 28513971
TI - Predictors and the distal outcome of general Internet use: The identification of
children's developmental trajectories.
AB - This study examined the predictors and distal outcome in relation to the
frequency of online activities and investigated the presence of prototypical
trajectories following different patterns of general Internet use over 5 years.
The data set consisted of a nationally representative sample of 2,840 fourth
graders (Mage = 9.86 years) in South Korea at baseline. Analyses revealed rank
order stability in general Internet use with four latent classes: high stable
(5.8%), high quadratic (20.3%), moderate stable (32.7%), and low stable (41.2%).
Youth with higher levels of perceived parental monitoring knowledge, friendship
closeness, and depressed mood at baseline were more likely to belong to the high
stable class, while girls were more likely to be in the high quadratic or
moderate stable classes relative to the low stable class. The high stable class
had the greatest odds of reporting alcohol use at grade eight, whereas the low
stable class had the lowest odds. Statement of contribution What is already known
on this subject? Internet usage increases as children progress through to early
adolescence and then levels off Longitudinal data have shown that adolescents'
greater Internet use is predictive of their higher levels of drinking What does
this study add? To explore different developmental pathways of Internet use in
relation to its antecedents and distal outcome Early adolescents who spend more
time on the Internet have a greater chance of starting to drink The
interindividual rank-order stability of general Internet usage exists at least
before late childhood.
PMID- 28513972
TI - Stigma in science: the case of earthquake prediction.
AB - This paper explores how earthquake scientists conceptualise earthquake
prediction, particularly given the conviction of six earthquake scientists for
manslaughter (subsequently overturned) on 22 October 2012 for having given
inappropriate advice to the public prior to the L'Aquila earthquake of 6 April
2009. In the first study of its kind, semi-structured interviews were conducted
with 17 earthquake scientists and the transcribed interviews were analysed
thematically. The scientists primarily denigrated earthquake prediction, showing
strong emotive responses and distancing themselves from earthquake 'prediction'
in favour of 'forecasting'. Earthquake prediction was regarded as impossible and
harmful. The stigmatisation of the subject is discussed in the light of research
on boundary work and stigma in science. The evaluation reveals how mitigation
becomes the more favoured endeavour, creating a normative environment that
disadvantages those who continue to pursue earthquake prediction research.
Recommendations are made for communication with the public on earthquake risk,
with a focus on how scientists portray uncertainty.
PMID- 28513973
TI - Width/Length Ratio in Maxillary Anterior Teeth. Comparative Study of Esthetic
Preferences among Professionals and Laypersons.
AB - PURPOSE: Many studies have examined the esthetic preferences of professionals in
the maxillary anterior region; however, only a few have taken into account the
ratios that are more frequent within the population or other ratios suggested in
the literature as ideal. Previous studies also failed to compare them with the
esthetic preferences of the lay population with regards to the smile. The purpose
of this study is to highlight the differences when perceiving the esthetics of
smiles between general dentists and laypersons, and linking them with the
width/length of the maxillary anterior teeth. MATERIALS AND METHODS: Photographs
of the full face of a female subject were modified with Photoshop CS regarding
the length/width relationships of the 6 maxillary anterior teeth. The three
modifications made were: (a) 80% length/width, (b) 85%, length/width, and (c) 85%
length/width in central incisors, 80% length/width in lateral incisors and
canines. Three sequences of photograph pairs were created with different ratios
and presented in PowerPoint to a sample of 100 general dentists and 100
laypersons. RESULTS: The ratio considered as the most esthetic by the majority of
the judges was 85% for central incisors and 80% for lateral incisors and canines,
with a statistically significant difference (p < 0.01). There was no
statistically significant difference in the esthetic preferences of the studied
populations either due to gender or professional experience of the dentists (p >
0.01). CONCLUSIONS: According to the results obtained in this study,
professionals and laypersons considered a width/length ratio of 85% for maxillary
central incisors and 80% for lateral incisors and canines as the most esthetic
for maxillary anterior teeth. These results do not support findings from other
studies previously published with similar ratios in central incisors, lateral
incisors, and canines. CLINICAL IMPLICATION: Today clinicians practice in a
treatment environment where not only function and utility but also esthetics is
demanded in almost every procedure. Restoring/maintaining function is considered
essential in any restorative dentistry treatment, but the esthetic aspects of any
treatment should never be forgotten. This study was motivated by the increasing
importance of obtaining a better appreciation of the perception of smile beauty,
and of the role of maxillary teeth width/length ratio on the perception of dental
esthetics.
PMID- 28513974
TI - Fecal microbiota transplantation outcomes in immunocompetent and
immunocompromised patients: A single-center experience.
AB - BACKGROUND: Clostridium difficile infection (CDI) is a major infectious disease
focus for which fecal microbiota transplantation (FMT) has been used with success
in various patient populations. METHODS: We conducted a retrospective study of
FMT in immunocompetent and immunocompromised patients to review outcomes at our
center, with a focus on identifying risk factors for FMT failure in solid organ
transplant (SOT) patients. FMT was conducted using universal banked frozen stool
via naso-duodenal tube in patients with recurrent CDI of 3 or more episodes per
our institutional protocol. RESULTS: Thirteen patients were included in the
analysis, 6 who were immunocompetent and 7 who were immunocompromised. Of these,
6 patients had a history of SOT and were primarily abdominal organ recipients.
All immunocompetent patients experienced success with FMT, while 3
immunocompromised SOT patients experienced failure. Two patients who failed FMT
had a second FMT, which was successful in one patient and failed in the second
patient. No adverse events were noted with FMT administration. A predictor of FMT
failure was antimicrobial exposure pre-FMT. CONCLUSIONS: This study highlights
the safe use of FMT for recurrent CDI with variable efficacy in immunocompromised
patients. Antimicrobial exposure prior to FMT was an identified risk factor for
FMT failure. The use of sequential FMT in SOT patients may be considered but
ultimately requires further investigation.
PMID- 28513975
TI - Opioids for the Treatment of Pain: The Risk of Treating a Multivariate Symptom.
PMID- 28513977
TI - Use of High Performance Polymers as Dental Implant Abutments and Frameworks: A
Case Series Report.
AB - Dental implant abutments can be made of different materials including titanium,
gold, zirconia, alumina, and polymeric materials. Polyetheretherketone (PEEK) is
a high performance thermoplastic polymer that can be used as a dental implant
abutment material. It has an elastic modulus comparable to bone and can reduce
stress shielding. PEEK is a radiolucent material that can allow better
radiographic imaging of peri-implant tissues and can be veneered with composite
materials or bonded to ceramics. PEEK is widely used in orthopedic and spinal
surgeries, and it possesses mechanical and biological characteristics that
encourage its use as dental implant abutments. This article will review the use
of PEEK in dentistry and in particular as a dental implant abutment and over
implant framework. Clinical reports will be presented to suggest some uses of
PEEK materials in implant dentistry.
PMID- 28513978
TI - Unilateral nevoid telangiectasia in two adolescents.
PMID- 28513976
TI - Gingerenone A Attenuates Monocyte-Endothelial Adhesion via Suppression of I Kappa
B Kinase Phosphorylation.
AB - During the early stages of atherosclerosis, monocytes bind and migrate into the
endothelial layer, promoting inflammation within the aorta. In order to prevent
the development of atherosclerosis, it is critical to inhibit such inflammation.
The therapeutic effects of ginger have been investigated in several models of
cardiovascular disease. However, although a number of previous studies have
focused on specific compounds, the mechanisms of action responsible remain
unclear. Here, we investigated five major compounds present in ginger, and
observed that gingerenone A exhibited the strongest inhibitory effects against
tumor necrosis factor (TNF)-alpha and lipopolysaccharide (LPS) induced monocyte
endothelial adhesion. Furthermore, gingerenone A significantly suppressed the
expression of TNF-alpha and LPS-induced vascular cell adhesion molecule-1 (VCAM
1) and chemokine (C-C motif) ligand 2 (CCL2), key mediators of the interaction
between monocytes, and endothelial cells. Transactivation of nuclear factor
kappaB (NF-kappaB), which is a key transcription factor of VCAM-1 and CCL2, was
induced by TNF-alpha and LPS, and inhibited by treatment of gingerenone A.
Gingerenone A also inhibited the phosphorylation of NF-kappaB inhibitor (IkappaB)
alpha and IkappaB Kinase. Taken together, these results demonstrate that
gingerenone A attenuates TNF-alpha and LPS-induced monocyte adhesion and the
expression of adhesion factors in endothelial cells via the suppression of NF
kappaB signaling. J. Cell. Biochem. 119: 260-268, 2018. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28513979
TI - Identification of a de novo variant in CHUK in a patient with an EEC/AEC syndrome
like phenotype and hypogammaglobulinemia.
AB - The cardinal features of Ectrodactyly, Ectodermal dysplasia, Cleft lip/palate
(EEC), and Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) syndromes
are ectodermal dysplasia (ED), orofacial clefting, and limb anomalies. EEC and
AEC are caused by heterozygous mutations in the transcription factor p63 encoded
by TP63. Here, we report a patient with an EEC/AEC syndrome-like phenotype,
including ankyloblepharon, ED, cleft palate, ectrodactyly, syndactyly, additional
hypogammaglobulinemia, and growth delay. Neither pathogenic mutations in TP63 nor
CNVs at the TP63 locus were identified. Exome sequencing revealed de novo
heterozygous variants in CHUK (conserved helix-loop-helix ubiquitous kinase),
PTGER4, and IFIT2. While the variant in PTGER4 might contribute to the
immunodeficiency and growth delay, the variant in CHUK appeared to be most
relevant for the EEC/AEC-like phenotype. CHUK is a direct target gene of p63 and
encodes a component of the IKK complex that plays a key role in NF-kappaB pathway
activation. The identified CHUK variant (g.101980394T>C; c.425A>G; p.His142Arg)
is located in the kinase domain which is responsible for the phosphorylation
activity of the protein. The variant may affect CHUK function and thus contribute
to the disease phenotype in three ways: (1) the variant exhibits a dominant
negative effect and results in an inactive IKK complex that affects the canonical
NF-kappaB pathway; (2) it affects the feedback loop of the canonical and non
canonical NF-kappaB pathways that are CHUK kinase activity-dependent; and (3) it
disrupts NF-kappaB independent epidermal development that is often p63-dependent.
Therefore, we propose that the heterozygous CHUK variant is highly likely to be
causative to the EEC/AEC-like and additional hypogammaglobulinemia phenotypes in
the patient presented here.
PMID- 28513980
TI - Solid-State Carbon Dots with Red Fluorescence and Efficient Construction of Dual
Fluorescence Morphologies.
AB - Stable solid-state red fluorescence from organosilane-functionalized carbon dots
(CDs) with sizes around 3 nm is reported for the first time. Meanwhile, a novel
method is also first reported for the efficient construction of dual-fluorescence
morphologies. The quantum yield of these solid-state CDs and their aqueous
solution is 9.60 and 50.7%, respectively. The fluorescence lifetime is 4.82 ns
for solid-state CDs, and 15.57 ns for their aqueous solution. These CDs are
detailedly studied how they can exhibit obvious photoluminescence overcoming the
self-quenching in solid state. Luminescent materials are constructed with dual
fluorescence based on as-prepared single emissive CDs (red emission) and
nonfluorescence media (starch, Al2 O3 , and RnOCH3 COONa), with the
characteristic peaks located at nearly 440 and 600 nm. Tunable photoluminescence
can be successfully achieved by tuning the mass ratio of CDs to solid matrix
(such as starch). These constructed dual-fluorescence CDs/starch composites can
also be applied in white light-emitting diodes with UV chips (395 nm), and oxygen
sensing.
PMID- 28513981
TI - Exposure to fermentation supernatant of Staphylococcus aureus accelerated
dedifferentiation of chondrocytes and production of antimicrobial peptides.
AB - Staphylococcus aureus (S. aureus) is the most popular pathogen found in septic
arthritis. Despite bacteria was eradicated from joint cavity during acute
infection, destruction of articular cartilage often continues for years, leading
to permanent joint damage. The mechanism responsible for this consistent
catabolic reaction in septic arthritis remains unclear. Here, we found that
fermentation supernatant (FS) of S. aureus accelerated dedifferentiation of
chondrocytes and induced expression of catabolic factors including A Disintegrin
like and Metalloproteinase with Thrombospondin-1 motifs 5, NO synthase 2, matrix
metalloproteinase-3, -13. In response to FS of S. aureus stimulation, expression
of antimicrobial peptides (AMPs) including beta-defensin-1, -2, -3, -4,
cathelicidin antimicrobial peptide (CAMP) in dedifferentiated chondrocytes was
significantly higher than that in chondrocytes which maintained their
differentiated phenotype. Among AMPs detected, expression of CAMP in
dedifferentiated chondrocytes was observed to increase 170 times higher than that
in differentiated ones. When exposed to FS of S. aureus, expression of
interleukin (IL)-1beta, IL-17F, and IL-22 were remarkably increased in
dedifferentiated chondrocytes. These results indicated that dedifferentiation of
chondrocytes caused by exposure to S. aureus might be responsible for secondary
osteoarthritis (OA) after acute S. aureus infection in joint. While, one
potential benefit of dedifferentiation resulted from S. aureus exposure is that
chondrocytes initiates a self-protective responsiveness by producing more AMPs
against bacterial infection. (c) 2017 Orthopaedic Research Society. Published by
Wiley Periodicals, Inc. J Orthop Res 36:443-451, 2018.
PMID- 28513982
TI - Plasmon Enhanced Fluorescence Based on Porphyrin-Peptoid Hybridized Gold
Nanoparticle Platform.
AB - A porphyrin-peptoid-hybridized silica-coated gold nanoparticle is developed,
which is inspired by the protein-chlorophyll ensemble found in photosynthetic
antenna. In the natural antenna, chlorophylls are integrated into dense
assemblies that are supported by frameworks of proteins, which ensure optimal
pigment arrangement for effective light harvesting. In the subject platform,
porphyrins are conjugated to the peptoid helix scaffold in a structurally well
defined alignments and subsequently immobilized on the surface of nanoparticles.
This prevents intermolecular aggregation among porphyrins and allows high
resolution analysis of the effect of porphyrin configuration on the optical
properties of the system. Interestingly, under the influence of plasmon from the
gold nanoparticle core, the fluorescence of porphyrin is enhanced up to 24-fold
at the wavelength where the plasmon resonance matches the porphyrin excitation
wavelength. In addition, differences in porphyrin configuration result in
spectral modification of their fluorescence emissions. Particularly, the peptoid
bearing two porphyrins at a distance of 6 A shows the most significant alteration
in fluorescence. The platform can facilitate extensive studies on the
relationship between porphyrin arrangement design and their photophysical
interaction in antenna complexes.
PMID- 28513984
TI - sPD-L1 Expression is Associated with Immunosuppression and Infectious
Complications in Patients with Acute Pancreatitis.
AB - Acute pancreatitis (AP) with infectious complications has high mortality because
of early-stage immunosuppression. The programmed cell death-1 (PD-1)/programmed
cell death ligand 1 (PD-L1) pathway is an important host immunosuppression
mechanism. Soluble PD-L1 (sPD-L1) expression regulates co-inhibitory signals in
malignancies or autoimmune disorders; however, its effects in AP are unknown.
Here, we evaluated whether serum sPD-L1 is involved in immune dysfunction and
assessed its relationship with infectious complications in early AP. Blood
samples were obtained from 56 patients with acute pancreatitis and 21 healthy
individuals in this prospective study. Serum sPD-L1 levels within 48 h after AP
onset were tested by enzyme-linked immunosorbent assays. Relevant immune
parameters (human leucocyte antigen-DR, lymphocyte count) and inflammatory
markers (C-reactive protein, white blood cell count) were analysed. sPD-L1 was
significantly upregulated in patients with early AP, especially those with
infectious complications, compared to healthy controls. Significant negative
correlations were observed among monocyte HLA-DR expression, lymphocyte count and
sPD-L1 levels in AP. Multivariate regression indicated that sPD-L1 was an
independent risk factor for infectious complications in AP. The findings suggest
that increased sPD-L1 expression appears to be involved in the development of
immunosuppression in the early stage of AP and that sPD-L1 might be an early
parameter for prediction of infectious complications in patients with AP.
PMID- 28513986
TI - Pleiotropic Effects of Chronic Phorbol Ester Treatment to Improve Glucose
Transport in Insulin-Resistant Cardiomyocytes.
AB - Stimulation of glucose transport is an important determinant of myocardial
susceptibility to ischemia and reperfusion. Stimulation of glucose transport is
markedly impaired in cardiomyocytes exposed to free fatty acids (FFA).
Deactivation of the Focal Adhesion Kinase (FAK) by FFA contributes to glucose
transport impairment, and could be corrected by chronic treatment with the
phorbol ester TPA. However, TPA must have effects in addition to FAK reactivation
to restore stimulated glucose transport. Chronic treatment with TPA improved
basal and stimulated glucose transport in FFA-exposed, but not in control
cardiomyocytes. Chronic FFA exposure induced the activation of PKCdelta and
PKCepsilon. TPA markedly downregulated the expression of PKCalpha, PKCdelta, and
PKCepsilon, suggesting that PKCdelta or PKCepsilon activation could contribute to
inhibition of glucose transport by FFA. Rottlerin, a specific PKCdelta inhibitor,
improved glucose transport in FFA-exposed cardiomyocytes; and PKCdelta was
reduced in the particulate fraction of FFA + TPA-exposed cardiomyocytes. TPA also
activated Protein Kinase D 1(PKD1) in FFA-exposed cardiomyocytes, as assessed by
autophosphorylation of PKD1 on Y916. Pharmaceutical inhibition of PKD1 only
partially prevented the improvement of glucose transport by TPA. Chronic TPA
treatment also increased basal and stimulated glycolysis and favored accumulation
of lipid droplets in FFA-exposed cardiomyocytes. In conclusion, basal and
stimulated glucose transport in cardiomyocytes is reduced by chronic FFA
exposure, but restored by concomitant treatment with a phorbol ester. The
mechanism of action of phorbol esters may involve downregulation of PKCdelta,
activation of PKD1 and a general switch from fatty acid to glucose metabolism. J.
Cell. Biochem. 9999: 4716-4727, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28513985
TI - Self-assembled nanofiber coatings for controlling cell responses.
AB - Nanofibers are thought to enhance cell adhesion, growth, and function. We
demonstrate that the choice of building blocks in self-assembling nanofiber
systems can be used to control cell behavior. The use of 2 D-coated, self
assembled nanofibers in controlling lens epithelial cells, fibroblasts, and
mesenchymal stem cells was investigated, focusing on gene and protein expression
related to the fibrotic response. To this end, three nanofibers with different
characteristics (morphology, topography, and wettability) were compared with two
standard materials frequently used in culturing cells, TCPS, and a collagen type
I coating. Cell metabolic activity, cell morphology, and gene and protein
expression were analyzed. The most hydrophilic nanofiber with more compact
network consisting of small fibers proved to provide a beneficial 2 D environment
for cell proliferation and matrix formation while decreasing the fibrotic/stress
behavior in all cell lines when compared with TCPS and the collagen type I
coating. This nanofiber demonstrates the potential to be used as a biomimetic
coating to study the development of fibrosis through epithelial-to-mesenchymal
transition. This study also shows that nanofiber structures do not enhance cell
function by definition, because the physico-chemical characteristics of the
nanofibers influence cell behavior as well and actually can be used to regulate
cell behavior toward suboptimal performance. (c) 2017 Wiley Periodicals, Inc. J
Biomed Mater Res Part A: 105A: 2252-2265, 2017.
PMID- 28513987
TI - Dermatological diseases in palliative care patients: a prospective study of 271
patients.
AB - BACKGROUND: Numerous risk factors place palliative care patients at an increased
risk of skin infections, dermatitis, and pressure sores. Furthermore, worsening
of chronic skin disorders can be expected, as well as the development of
treatment-induced and malignancy-related dermatoses. The objective of the present
study was to investigate the prevalence and treatment of dermatological
conditions in patients receiving hospital-based palliative care. METHODS: Two
hundred seventy-one palliative patients were enrolled. All assessments were
conducted by dermatologists. Skin lesions were classified into seven categories:
infections, skin tumors, dermatitis, chronic wounds, nail and hair disorders,
pruritus, and other unclassified conditions. Treatment modalities were classified
as topical only or systemic. RESULTS: Overall, 1,267 dermatological conditions
were recorded, 49 % of which were hospital-acquired. All patients had at least
one dermatological condition, and more than 50 different dermatological disorders
were noted. The most common group of skin disorders was dermatitis (18.3 % of all
dermatological conditions), followed by nail and hair disorders (17.5 %). Almost
16 % of dermatological conditions were treated systemically. CONCLUSIONS:
Dermatological conditions are a common and clinically significant problem for
palliative patients. The inclusion of dermatologists in multidisciplinary
palliative teams should prove helpful in the management of these patients.
PMID- 28513988
TI - Aquagenic cutaneous disorders.
AB - Aquagenic cutaneous disorders, which include aquagenic urticaria, aquagenic
pruritus, and aquagenic acrokeratoderma, are a group of rare diseases
characterized by skin lesions or discomfort induced by brief contact with water.
Aquagenic urticaria is characterized by pruritic wheals that occur at the sites
of water contact, either immediately or within minutes, and disappear within 30
60 min after water removal. Aquagenic pruritus presents with severe pruritus or a
stinging, tingling, or burning sensation without any visible skin changes. These
symptoms occur immediately or within minutes after the skin is exposed to water,
lasting for one hour or longer. Aquagenic acrokeratoderma usually presents with
whitish papules and plaques, edema, and hyperwrinkling within 2-20 min after
brief exposure to water; symptoms disappear within minutes to one hour after
drying. The pathomechanisms of these diseases are not yet fully understood, and
their diagnosis is primarily based on clinical features. Treatment remains a
challenge. Herein, we review the literature regarding these unusual disorders.
PMID- 28513989
TI - Graphene/dodecanol floating solidification microextraction for the
preconcentration of trace levels of cinnamic acid derivatives in traditional
Chinese medicines.
AB - A novel graphene/dodecanol floating solidification microextraction followed by
HPLC with diode-array detection has been developed to extract trace levels of
four cinnamic acid derivatives in traditional Chinese medicines. Several
parameters affecting the performance were investigated and optimized. Also,
possible microextraction mechanism was analyzed and discussed. Under the optimum
conditions (amount of graphene in dodecanol: 0.25 mg/mL; volume of extraction
phase: 70 MUL; pH of sample phase: 3; extraction time: 30 min; stirring rate:
1000 rpm; salt amount: 26.5% NaCl; volume of sample phase: 10 mL, and without
dispersant addition), the enrichment factors of four cinnamic acid derivatives
ranged from 26 to 112, the linear ranges were 1.0 * 10-2 -10.0 MUg/mL for caffeic
acid, 1.3 * 10-3 -1.9 MUg/mL for p-hydroxycinnamic acid, 2.8 * 10-3 -4.1 MUg/mL
for ferulic acid, and 2.7 * 10-3 -4.1 MUg/mL for cinnamic acid, with r2 >=
0.9993. The detection limits were found to be in the range of 0.1-1.0 ng/mL, and
satisfactory recoveries (92.5-111.2%) and precisions (RSDs 1.1-9.5%) were also
achieved. The results showed that the approach is simple, effective and sensitive
for the preconcentration and determination of trace levels of cinnamic acid
derivatives in Chinese medicines. The proposed method was compared with
conventional dodecanol floating solidification microextraction and other
extraction methods.
PMID- 28513990
TI - Network Meta-Analysis on the Effects of DNA Damage Response-Related Gene
Mutations on Overall Survival of Breast Cancer Based on TCGA Database.
AB - The study was conducted for comparing the effects of 12 DNA damage response gene
mutations (CHEK1, CHEK2, RAD51, BRCA1, BRCA2, MLH1, MSH2, ATM, ATR, MDC1, PARP1,
and FANCF) on the overall survival (OS) of breast cancer (BC) patients. We
searched the Cancer Genome Atlas (TCGA) database from inception to September
2016. Studies that investigated the association between 12 DNA damage responses
related genes and BC consolidated into this Network meta-analysis, by comparing
directly or indirectly to evaluate the hazard rate (HR) value and the surface
under the cumulative sequence ranking curves (SUCRA). In total four articles were
involved. Our results demonstrated 12 DNA damage response gene mutations were
associated to the poor prognosis of BC patients (CHEK1: HR = 9.9, 95%CI = 3.6
26.0; CHEK2: HR = 6.9, 95%CI = 3.1-15.0; RAD51: HR = 5.8, 95%CI = 2.2-15.0;
BRCA1: HR = 2.8, 95%CI = 1.3-6.1; BRCA2: HR = 3.9, 95%CI = 2.0-7.7; MLH1: HR =
11.0, 95%CI = 3.4-33.0; MSH2: HR = 6.5, 95%CI = 2.1-20.0; ATM: HR = 5.6, 95%CI =
2.6-12.0; ATR: HR = 2.9, 95%CI = 1.3-6.9; MDC1: HR = 15.0, 95%CI = 5.0-45.0;
PARP1: HR = 3.4, 95%CI = 1.8-6.6; FANCF: HR = 6.0, 95%CI = 1.8-20.0). SUCRA
results revealed that the mutation of MDC1 gene was related to the worst
prognosis in patients with BC (SUCRA = 17.32%). DNA damage response gene
mutations were associated to the poor prognosis in patients with BC and the BC
patients with MDC1 gene mutation had the worst prognosis. J. Cell. Biochem. 118:
4728-4734, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28513992
TI - Immunoregulatory protein B7-H3 promotes growth and decreases sensitivity to
therapy in metastatic melanoma cells.
AB - B7-H3 (CD276) belongs to the B7 family of immunoregulatory proteins and has been
implicated in cancer progression and metastasis. In this study, we found that
metastatic melanoma cells with knockdown expression of B7-H3 showed modest
decrease in proliferation and glycolytic capacity and were more sensitive to
dacarbazine (DTIC) chemotherapy and small-molecule inhibitors targeting MAP
kinase (MAPK) and AKT/mTOR pathways: vemurafenib (PLX4032; BRAF inhibitor),
binimetinib (MEK-162; MEK inhibitor), everolimus (RAD001; mTOR inhibitor), and
triciribidine (API-2; AKT inhibitor). Similar effects were observed in melanoma
cells in the presence of an inhibitory B7-H3 monoclonal antibody, while the
opposite was seen in B7-H3-overexpressing cells. Further, combining B7-H3
inhibition with small-molecule inhibitors resulted in significantly increased
antiproliferative effect in melanoma cells, as well as in BRAFV600E mutated cell
lines derived from patient biopsies. Our findings indicate that targeting B7-H3
may be a novel alternative to improve current therapy of metastatic melanoma.
PMID- 28513991
TI - Immunoprotective Effect of Chitosan Particles on Hymenolepis nana - Infected
Mice.
AB - Hymenolepis nana is the most commonly known intestinal cestode infecting mainly
human. This study aimed to investigate the potential effect of chitosan particles
(CSP) to enhance the immune system against H. nana infection. Determination of
worm burden, egg output, histopathological changes, oxidative stress markers
(lipid peroxidation and reduced glutathione), goblet (GCs) and mucosal mast cells
(MMCs) counts in intestinal ileum was performed. In addition, levels of
intestinal mRNA expression of interleukin (IL)-4, IL-9, stem cell factor (SCF),
type I and II interferons (IFN)-alpha/ gamma, tumour necrosis factor (TNF)-alpha,
mucin 2 (MUC2) and inducible nitric oxide synthase (iNOs) were investigated using
real-time PCR. The results indicated induced reductions in adult worm and egg
counts in infected mice after CSP treatment. This was associated with improvement
in tissue morphometric measurements and oxidative stress which were altered after
infection. Expression levels of iNOs, IFN-alpha, IFN-gamma, TNF-alpha and IL-9
were decreased by CSP. Conversely, expression levels of MUC2, IL-4 and SCF
increased compared to infected untreated group. In addition, GCs and MMCs counts
were normalized by CSP. In conclusion, this study could indicate the
immunoprotective effect of CSP against H. nana infection. This was characterized
with Th2 anti-inflammatory responses.
PMID- 28513993
TI - Patient reported outcomes in orthopaedics.
AB - Patient reported outcome measures (PROMs) are key tools when performing clinical
research and PROM data are increasingly used to inform clinical decision-making,
patient-centered care, health policy and more recently, reimbursement decisions.
PROMs must possess particular properties before they are used. Thus purpose of
this paper is to give an overview of PROMs, their definition, how their evidence
can be assessed, how they should be reported in clinical research, how to choose
PROMs, the types of PROMs available in orthopaedics, where these measures can be
found, PROMs in orthopaedic clinical practice and what are some key next steps in
this field. If PROMs are used in accordance with the guidance in this article, I
believe we will gain considerable insight into PROMs in orthopaedics and will
advance this field in a way that can contribute to science, improve patient care
and save considerable resources. (c) 2017 Orthopaedic Research Society. Published
by Wiley Periodicals, Inc. J Orthop Res 35:2098-2108, 2017.
PMID- 28513994
TI - Ultrahigh-Conductivity Polymer Hydrogels with Arbitrary Structures.
AB - A poly(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS) hydrogel
is prepared by thermal treatment of a commercial PEDOT:PSS (PH1000) suspension in
0.1 mol L-1 sulfuric acid followed by partially removing its PSS component with
concentrated sulfuric acid. This hydrogel has a low solid content of 4% (by
weight) and an extremely high conductivity of 880 S m-1 . It can be fabricated
into different shapes such as films, fibers, and columns with arbitrary sizes for
practical applications. A highly conductive and mechanically strong porous fiber
is prepared by drying PEDOT:PSS hydrogel fiber to fabricate a current-collector
free solid-state flexible supercapacitor. This fiber supercapacitor delivers a
volumetric capacitance as high as 202 F cm-3 at 0.54 A cm-3 with an extraordinary
high-rate performance. It also shows excellent electrochemical stability and high
flexibility, promising for the application as wearable energy-storage devices.
PMID- 28513995
TI - Inner strength and its relationship to health threats in ageing-A cross-sectional
study among community-dwelling older women.
AB - AIM: To explore the relationship between inner strength and health threats among
community-dwelling older women. BACKGROUND: Inner strength is described as a
resource that promotes experiences of health, despite adversities. Inner strength
and its dimensions (i.e. connectedness, creativity, firmness and flexibility) can
be assessed using the Inner Strength Scale (ISS). Exploring attributes of weaker
inner strength may yield valuable information about areas to focus on in
enhancing a person's inner strength and may ultimately lead to the perception of
better health. DESIGN: Cross-sectional questionnaire survey. METHODS: The study
is based on responses from 1270 community-dwelling older women aged 65 years and
older; these were collected in the year 2010 and describe the situation that
still exists today for older women. The questionnaire included the ISS,
background characteristics and explanatory variables known to be health threats
in ageing. Data were analysed using descriptive and inferential statistics.
RESULTS: Poorer mental health was related to weaker inner strength in total and
in all the dimensions. Symptoms of depressive disorders and feeling lonely were
related to three of the dimensions, except firmness and creativity respectively.
Furthermore, poor physical health was associated with the dimensions firmness and
flexibility. Other health threats were significantly related to only one of the
dimensions, or not associated at all. CONCLUSION: Mental ill health has overall
the strongest association with weaker inner strength. Longitudinal studies are
recommended to confirm the results. However, the ISS does not only estimate inner
strength but can also be a tool for discovering where (i.e. dimension)
interventions may be most profitable.
PMID- 28513996
TI - Conformational Dynamics of mRNA in Gene Expression as New Pharmaceutical Target.
AB - Gene expression involves concurrent and consecutive events of unidirectional
nature, such as transcription occurring from 5' to 3' end and translation from N
to C terminus. Recent functional studies have shown the importance of kinetically
coupled nucleic acid folding events that influence gene expression processes. For
example, mRNA conformational dynamics during transcription and translation
regulate gene expression and subsequent protein functionalization. The structure,
stability, and kinetic properties of nucleic acids are sensitive to the
intracellular molecular environment and can be regulated by using artificially
developed molecules. Here, we review our current understanding of how mRNA
conformational dynamics affect the consecutive and concurrent processes involved
in gene expression and discuss how novel pharmaceutical agents designed to
influence RNA conformational dynamics, could be developed to treat various
diseases.
PMID- 28513997
TI - Efficient Fusion of Liposomes by Nucleobase Quadruple-Anchored DNA.
AB - Anchoring DNA via hydrophobic units into the membrane of vesicles allows tagging
of these nanocontainers with sequence information. Moreover, the hybridization of
DNA on the surface of liposomes enables sequence specific functionalization,
vesicle aggregation, and vesicle fusion. Specifically, DNA-hybridization-based
approaches for fusion employing oligonucleotides terminally modified with one or
two anchoring units were hindered by a limited degree of full fusion or by
significant leakage during fusion. The current work deals with a new strategy for
anchoring oligonucleotides on a membrane by lipid-modified nucleobases rather
than by attaching hydrophobic units to the 3'- or 5'-termini. The lipid anchors
were incorporated into the DNA sequence via phosphoramidite nucleotide building
blocks during automated solid-phase synthesis allowing variation of the number
and position of hydrophobic units along the DNA backbone. Single-stranded DNA
functionalized with four lipid-modified nucleobases was stably grafted onto the
membrane of lipid vesicles. It was found that the orientation of DNA
hybridization and the number of anchoring units play a crucial role in liposomal
fusion, which in the most efficient system reached remarkable 29 % content mixing
without notable leakage.
PMID- 28513998
TI - Inflammatory bowel disease caused by primary immunodeficiencies-Clinical
presentations, review of literature, and proposal of a rational diagnostic
algorithm.
AB - Inflammatory bowel diseases (IBD) including Crohn's disease (CD) and ulcerative
colitis have a multifactorial pathogenesis with complex interactions between
polygenetic predispositions and environmental factors. However, IBD can also be
caused by monogenic diseases, such as primary immunodeficiencies (PID). Recently,
an increasing number of these altogether rare diseases have been described to
present often primarily, or solely, as IBD. Early recognition of these conditions
enables adaption of therapies and thus directly benefits the course of IBDs.
Here, we discuss the different clinical presentations in IBD and characteristic
features of patient's history, clinical findings, and diagnostic results
indicative for a causative PID. Possible predictors are early onset of disease,
necessity of parenteral nutrition, failure to respond to standard
immunosuppressive therapy, parental consanguinity, increased susceptibility for
infections, certain histopathologic findings, and blood tests that are atypical
for classic IBD. We illustrate this with exemplary case studies of IBD due to
NEMO deficiency, chronic granulomatous disease, common variable immunodeficiency,
CTLA-4 and LRBA deficiency. Taking these factors into account, we propose a
diagnostic pathway to enable early diagnosis of IBD due to PID.
PMID- 28513999
TI - Microparticles of healthy origins improve endothelial progenitor cell dysfunction
via microRNA transfer in an atherosclerotic hamster model.
AB - AIM: In this study, we aimed: (i) to obtain and functionally characterize the
cultures of late endothelial progenitor cells (EPCs) from the animal blood; (ii)
to investigate the potential beneficial effects of circulating microparticles
(MPs) of healthy origins on EPC dysfunctionality in atherosclerosis as well as
involved mechanisms. METHODS: Late EPCs were obtained and expanded in culture
from peripheral blood isolated from two animal groups: hypertensive
hyperlipidaemic (HH) and control (C) hamsters. In parallel experiments, late EPC
cultures from HH were incubated with MPs from C group. RESULTS: The results
showed that late EPCs display endothelial cell phenotype: (i) have ability to
uptake 1,1-dioctadecyl-3,3,3,3 tetramethylindocarbocyanine-labelled acetylated
low-density lipoprotein and Ulex europaeus agglutinin lectin-1; (ii) express
CD34, CD133, KDR, CD144, vWF, Tie-2. Late EPCs from HH exhibited different
morphological and functional characteristics compared to control: (i) are smaller
and irregular in shape; (ii) present decreased endothelial surface marker
expression; (iii) display reduced proliferation, migration and adhesion; (iv)
lose ability to organize themselves into tubular structures and integrate into
vascular network; (v) have diminished function of inward rectifier potassium
channels. The incubation of late EPCs with MPs improved EPC functionality by miR
10a, miR-21, miR-126, miR-146a, miR-223 transfer and IGF-1 expression activation;
the kinetic study of MP incorporation into EPCs demonstrated MP uptake by EPCs
followed by the miRNA transfer. CONCLUSION: The data reveal that late EPCs from
atherosclerotic model exhibit distinctive features and are dysfunctional, and
their function recovery can be supported by MP ability to transfer miRNAs. These
findings bring a new light on the vascular repair in atherosclerosis.
PMID- 28514001
TI - Nutritional assessment of hospital patients: New methods and new opportunities.
AB - Recently, two new methods (total body electrical conductivity [TOBEC] and
bioelectrical impedance analysis [BIA]) have become available for the rapid,
safe, and convenient estimation of total body water in hospital patients. Despite
these clear advantages, the clinical usefulness of the TOBEC and BIA methods in
patient diagnosis and care is likely to be restricted by illness-related changes
in the hydration of the lean body and in the distribution of water between the
intracellular and extracellular water compartments. If these methods can be
refined so as to permit their measurement of extracellular water as rapidly as
they now measure total body water, the ability of clinicians to assess and
monitor the nutritional and metabolic status of their hospital patients will be
greatly enhanced.
PMID- 28514002
TI - Evidence for continuing secular increase in height within families in the United
States.
AB - Measures of mature heights of the second generation of longitudinal subjects in
the Fels Institute growth study are now becoming available. When augmented by the
heights of the parents who enrolled the first-generation children, these families
provide three-generation data for mature height. Heights of the first-generation
spouses are also available. The successive generations correspond approximately
to the following birth cohorts: 1886-1920, 1921-1949, and 1950-1968. Also
available in the Fels data are heights for two-generation families with parents
and offspring in successive cohorts. In the three-generation families, the mean
increases (cm) for 34 grandmothers, mothers, and daughters were 2.99 and 2.77,
both significant with P < 0.01; for 14 grandfathers, fathers and sons, 3.15 and
3.63, the latter significant with P < 0.05. In the first and second cohort two
generation families, the mean increase for 67 mothers and daughters was 4.01 (P <
0.01); for 62 fathers and sons, 3.84 (P < 0.01). In the second and third cohorts,
the corresponding figures for 53 and 52 pairs were 3.00 and 4.36, both P < 0.01.
In every case, the change in the rate of increase between the first and second
generation cohort, and that between the second and third, was not statistically
significant. There is no clear evidence that the secular increase in height is
decreasing in these families. The finding must be qualified, however, by the
observation that most of the first-generation subjects grew to maturity during
the Great Depression, when nutrition may have suffered relative to that of the
post-World War II years of the maturing second generation. Study of a third
generation of Fels subjects may be necessary before a decrease in the secular
trend becomes evident in this sample.
PMID- 28514000
TI - Long-term outcomes and recurrence patterns of standard versus extended
pancreatectomy for pancreatic head cancer: a multicenter prospective randomized
controlled study.
AB - BACKGROUND: Our previous randomized controlled trial revealed no difference in 2
year overall survival (OS) between extended and standard resection for pancreatic
adenocarcinoma. The present study evaluated the 5-year OS and recurrence patterns
according to the extent of pancreatectomy. METHODS: Between 2006 and 2009, 169
consecutive patients were prospectively enrolled and randomized to standard (n =
83) or extended resection (n = 86) groups to compare 5-year OS rate, long-term
recurrence patterns and factors associated with long-term survival. RESULTS: The
surgical R0 rate was similar between the standard and extended groups (85.5 vs.
90.7%, P = 0.300). Five-year OS (18.4 vs. 14.4%, P = 0.388), 5-year disease-free
survival (14.8 vs. 14.0%, P = 0.531), and overall recurrence rates (74.7 vs.
69.9%, P = 0.497) were not significantly different between the two groups,
although the incidence of peritoneal seeding was higher in the extended group (25
vs. 8.1%, P = 0.014). CONCLUSIONS: Extended pancreatectomy does not have better
short-term and long-term survival outcomes, and shows similar R0 rates and
overall recurrence rates compared with standard pancreatectomy. Extended
pancreatectomy does not have to be performed routinely for all cases of
resectable pancreatic adenocarcinoma, especially considering its associated
increased morbidity shown in our previous study.
PMID- 28514004
TI - Symposium in honor of Alex Roche.
PMID- 28514003
TI - Statistical estimation of skeletal maturity.
AB - Given a number of developing aspects of the skeletal system that may be used as
indicators of maturity, some combination rule is required to produce a single
numerical description of skeletal maturity from data on several such indicators.
In the RWT system for estimation of skeletal maturity from indicators in the
knee, a nonlinear statistical model for graded data is used for this purpose. In
the application of a similar model in the FELS system for the hand-wrist, the
estimation procedure was extended to include continuous as well as graded
indicators. This paper describes the statistical estimation procedure used, with
illustrations drawn from the hand-wrist system.
PMID- 28514005
TI - Discussion.
PMID- 28514006
TI - The FELS method of assessing the skeletal maturity of the hand-wrist.
AB - The FELS method of assessing the skeletal maturity of the hand-wrist differs from
the Greulich-Pyle and Tanner-Whitehouse methods in the observations made, the
provision of a range of shapes to which maturity indicator grades can be assigned
and in the statistical methods used to construct the scale of skeletal maturity.
The FELS method for the hand-wrist was developed using 13,823 serial radiographs
of the left hand-wrist of boys and girls in the Fels Longitudinal Study. One
hundred-thirty possible indicators were originally identified. Eighty-five graded
and 13 metric indicators were selected on the basis of an indicator's ability to
discriminate between children at the same chronological age, its universal
appearance, reliability, validity, and completeness. The subset of FEELS maturity
indicators assessed at a chronological age are analyzed with a microcomputer
program that provides the skeletal age and the standard error of the estimate for
that skeletal age. Comparison among hand-wrist skeletal age assessments for
children in the Fels Longitudinal Study by the FELS, Greulich-Pyle, and Tanner
Whitehouse methods indicate that the FELS method is the more appropriate method
for the present population of United States children.
PMID- 28514007
TI - Maturity and its relationship to plasma lipid and lipoprotein levels in
adolescents: The Fels longitudinal study.
AB - During adolescence, changes in lipid and lipoprotein levels have been reported to
be associated with changes in body composition and changes in endogenous
testosterone and estradiol. These hormone levels are directly correlated with
sexual and skeletal maturity levels. The purpose of the present study was to
determine if there are associations during pubescence and adolescence,
independent of chronological age, between measures of maturity and body
composition or plasma lipid and lipoprotein cholesterols. Skeletal maturity was
measured on the basis of skeletal assessments of the bones of the knee joint. Age
at peak height velocity was determined from serial stature measurements and, in
girls, age at menarche was recorded. These measures of maturity, as well as
measures of percent body fat, total body fat, total body fat mass, fat-free mass
from underwater weighing, and plasma cholesterol, triglyceride, highdensity
lipoprotein-cholesterol, and low-density lipoprotein-cholesterol levels from 502
observations on 174 boys and girls enrolled in the Fels Longitudinal Study were
used in the analysis. Within annual chronological age groups, no associations
were found between level of maturity and lipid and lipoprotein level or percent
body fat in boys or girls. However, changes in lipid and lipoprotein levels over
time appeared to be more apparent when age grouping were based on skeletal age
than when they were based on chronological age.
PMID- 28514008
TI - Resistant cross- age smoothing of age-specific percentiles for growth reference
data.
AB - Resistant delineation, a technique adapted from exploratory data analysis (Tukey,
Exploratory Data Analysis, 1977), was applied to smooth age-specific percentiles
for triceps skinfold thickness across ages from 1 to 20 years. Row percentiles
were transformed to logarithms to promote symmetry and to render variability more
nearly homogeneous across ages. The delineation involved smoothing resistantly
the sequences of age-specific log medians and the sequence of age-specific
positive differences between the "4253H, twice" (Velleman, J. Am. Statist.
Assoc., 75:609-615, 1980). The delineation concluded by recombining these
smoothed sequences to obtain smoothed percentiles in the log scale. Finally, the
logarithmic transformation was reversed, yielding the smoothed age-specific
percentiles. Comparisons of smoothed results from resistant, delineation with the
original data indicated a satisfactory fit. Comparisons with published smoothed
percentiles, obtained from the same data by a cubic-spline procedure, showed that
the resistant delineation captured the structure of the raw data better than the
cubic-spline procedure. The resistant delineation procedure makes few assumptions
of the underlying data, it ensures a proper order relationship among the smoothed
percentiles, it is relatively insensitive to isolated unusual data, and it is
available in a common software package.
PMID- 28514009
TI - Concept of chemical immaturity in body composition estimates: Implications for
estimating the prevalence of obesity in childhood and youth.
AB - This paper estimates the prevalence of obesity in 6-8-year-old children, 13-15
year-old youth, and 18-19-old adults by using skinfold data of the National
Nutrition and Health Examination Survey. Obesity is defined as above 25% fat in
males and above 32% fat in females. Skinfold equations used to estimate the fat
cotent at each age were based on a multicompontent approach that used body
density, body water, and bone mineral. The prevalence of obesity in the U.S.
population was found to be much lower in children than in youth and young adults
and to increase from 1 in 20 in childhood to 1 in 5 in adulthood.
PMID- 28514010
TI - Cohabitation, activity level, and energy intake in parent-child resemblance for
selected biological traits.
AB - Activity level and energy intake were estimated from 3-day records, including a
weekend day, in parents and children from families of French descent.
Subcutaneous fat from the summation of six skinfolds, fasting serum
triglycerides, total and high-density lipoprotein cholesterol, and submaximal
power output (PWC150 ) derived from a cycle ergometer test also were determined
in these subjects. Dependent variables were normalized through log10 or squre
root transformation, and scores were adjusted by generation for the effects of
age and gender. Correlations with residual scores were performed with pairs of
natural parents and child (N ? 1057) and pairs of foster parent and adopted child
(N ? 283). Coefficients were generally little affected by statistical control
over current activity level and energy intake. Pairs of biological relatives were
classified as either very similar (25% of pairs) or very dissimilar (25% of
pairs) in terms of energy intake or activity level. Correlations revealed that
similarity or discordance in energy intake or activity level had only a slight
effect on parent-child resemblance. In addition, duration of cohabitation had
little influence on parent-child covariation. It was concluded that parent-child
resemblance in subcutaneous fat, work capacity, and blood lipids are not
significantly affected by current patterns of energy intake, activity level, or
duration of cohabitation.
PMID- 28514011
TI - Method for analyzing complex two-dimensional forms: Elliptical Fourier functions.
AB - A generalized procedure, elliptical Fourier analysis, for accurately
characterizing the shape of complex morphological forms of the type commonly
encountered in the biological sciences, is described. Elliptical Fourier
functions are derived as a parametric formulation from conventional Fourier
analysis, i.e., as a pair of equations that are functions of a third variable.
The use of elliptical Fourier functions circumvents three restrictions that have
limited conventional Fourier analysis to certain classes of shapes. These
restrictions are (1) equal divisions over the interval or period; (2) dependency
on the coordinate system, i.e., conventional Fourier functions are not
"coordinate free"; and (3) the presence of shapes with outlines that curve back
on themselves, a common occurrence. These three limitations are effectively
removed with the utilization of elliptical Fourier functions, facilitating the
analysis of a much larger class of two-dimensional forms.
PMID- 28514012
TI - Growth and maturity status of black and white children classified as obese by
different criteria.
AB - Weight, stature, bicondylar and biepicondylar breadths, estimated midarm muscle
circumference, grip strength, and skeletal maturity were compared in 111 obese
Black and 120 obese White children, 6 through 12 years of age. The children were
classified as obese by the triceps skinfold (TSF), body mass index (BMI), or
both, and were labeled, respectively as TSF Obese, BMI Obese, and BMI+TSF Obese.
The anthropmetric dimensions, including grip strength, were transformed to z
scores on the basis of age-, sex-, and race-specific means and standard
deviations for a mixed longitudinal sample of children among whom the obese
children were indentified. Skeletal maturityu was expressed as the diference
between skeletal age (Tanner-Whitehouse II RUS method) and chronological age.
Within each racial group, BMI+TSF Obese are heavier and taller, have larger
extremity bone widths, have larger estimated midarm musculature, are stronger,
and are more advanced in skeletal maturity than TSF Obese and average nonobese
children. Although the number of children classified as BMI Obese is small, their
apparently unique characteristic is an especially large estimated midarm muscle
circumference compared to other obese children.
PMID- 28514015
TI - Preparation of Mesoporous Basic Oxides through Assembly of Monodispersed Mg-Al
Layered Double Hydroxide Nanoparticles.
AB - Mesoporous basic Mg-Al mixed metal oxides (MMOs) with a high surface area and
large pore size have been prepared through the assembly of monodispersed layered
double hydroxide nanoparticles (LDHNPs) with block copolymer templates. The
particle sizes of the LDHNPs were mainly controlled by varying the concentration
of tris(hydroxymethyl)aminomethane (THAM), which was used as a surface
stabilizing agent. LDHNPs and micelles of a block copolymer (Pluronic F127) were
assembled to form a composite. The composites were calcined to transform them
into mesoporous MMOs and to remove the templates. The Brunauer-Emmett-Teller
surface areas, mesopore sizes, and pore volumes increased as a result of using
the templates. Moreover, the pore sizes of the mesoporous MMOs could be
controlled by using LDHNPs of different sizes. The mesoporous MMOs prepared from
the LDHNPs showed much higher catalytic activity than a conventional MMO catalyst
for the Knovenagel condensation of ethyl cyanoacetate with benzaldehyde. The
mesoporous MMO catalyst prepared using the smallest LDHNPs, about 12 nm in size,
showed the highest activity. Therefore, the use of monodispersed LDHNPs and
templates is effective for preparing highly active mesoporous solid base
catalysts.
PMID- 28514014
TI - Repeatability of vessel density measurement in human skin by OCT-based
microangiography.
AB - PURPOSE: To investigate the repeatability of vessel density measurement at human
arm skin in healthy subjects with OCT-based microangiography (OMAG). METHODS:
Four locations including volar wrist, volar forearm, shoulder, and volar upper
arm were scanned using an optimized swept source OCT system, working at center
wavelength of 1300 nm and A-line rate of 100 kHz. Three scans were acquired at
each location at the same visit. Vascular images of papillary dermis, reticular
dermis, and the whole dermis layer were generated with OMAG processing and
automatic segmentation algorithms. The vessel density (VD) of each layer was
calculated based on vascular images, and the repeatability of the VD at the same
physiological location was thereafter assessed. RESULTS: Fifteen healthy
volunteers were included. High repeatability of VD was found for wrist, forearm,
shoulder, and upper arm (coefficient of variation (CV)=2.4, 2.7, 2.7, 2.0, and
intraclass correlation coefficient (ICC)=0.906, 0.854, 0.943, 0.916
respectively). The VD measurements showed no significant difference between the
four locations in any of the three layers, ie papillary layer (P=.1063),
reticular layer (P=.3371), and whole dermis layer (P=.3233). CONCLUSION:
Quantification of VD by using OCT/OMAG is repeatable when imaging skin tissue
beds in healthy individuals.
PMID- 28514013
TI - Antimicrobial Prescribing in Dogs and Cats in Australia: Results of the
Australasian Infectious Disease Advisory Panel Survey.
AB - BACKGROUND: Investigations of antimicrobial use in companion animals are limited.
With the growing recognition of the need for improved antimicrobial stewardship,
there is urgent need for more detailed understanding of the patterns of
antimicrobial use in this sector. OBJECTIVES: To investigate antimicrobial use
for medical and surgical conditions in dogs and cats by Australian veterinarians.
METHODS: A cross-sectional study was performed over 4 months in 2011. Respondents
were asked about their choices of antimicrobials for empirical therapy of
diseases in dogs and cats, duration of therapy, and selection based on culture
and susceptibility testing, for common conditions framed as case scenarios: 11
medical, 2 surgical, and 8 dermatological. RESULTS: A total of 892 of the 1,029
members of the Australian veterinary profession that completed the survey
satisfied the selection criteria. Empirical antimicrobial therapy was more common
for acute conditions (76%) than chronic conditions (24%). Overall, the most
common antimicrobial classes were potentiated aminopenicillins (36%),
fluoroquinolones (15%), first- and second-generation cephalosporins (14%), and
tetracyclines (11%). Third-generation cephalosporins were more frequently used in
cats (16%) compared to dogs (2%). Agreement with Australasian Infectious Disease
Advisory Panel (AIDAP) guidelines (generated subsequently) was variable ranging
from 0 to 69% between conditions. CONCLUSIONS AND CLINICAL IMPORTANCE: Choice of
antimicrobials by Australian veterinary practitioners was generally appropriate,
with relatively low use of drugs of high importance, except for the empirical use
of fluoroquinolones in dogs, particularly for otitis externa and 3rd-generation
cephalosporins in cats. Future surveys will determine whether introduction of the
2013 AIDAP therapeutic guidelines has influenced prescribing habits.
PMID- 28514017
TI - Isopimaric acid - a multi-targeting ion channel modulator reducing excitability
and arrhythmicity in a spontaneously beating mouse atrial cell line.
AB - AIM: Atrial fibrillation is the most common persistent cardiac arrhythmia, and it
is not well controlled by present drugs. Because some resin acids open voltage
gated potassium channels and reduce neuronal excitability, we explored the
effects of the resin acid isopimaric acid (IPA) on action potentials and ion
currents in cardiomyocytes. METHODS: Spontaneously beating mouse atrial HL-1
cells were investigated with the whole-cell patch-clamp technique. RESULTS: 1-25
MUmol L-1 IPA reduced the action potential frequency by up to 50%. The effect of
IPA on six different voltage-gated ion channels was investigated; most voltage
dependent parameters of ion channel gating were shifted in the negative direction
along the voltage axis, consistent with a hypothesis that a lipophilic and
negatively charged compound binds to the lipid membrane close to the positively
charged voltage sensor of the ion channels. The major finding was that IPA
inactivated sodium channels and L- and T-type calcium channels and activated the
rapidly activating potassium channel and the transient outward potassium channel.
Computer simulations of IPA effects on all of the ion currents were consistent
with a reduced excitability, and they also showed that effects on the Na channel
played the largest role to reduce the action potential frequency. Finally,
induced arrhythmia in the HL-1 cells was reversed by IPA. CONCLUSION: Low
concentrations of IPA reduced the action potential frequency and restored regular
firing by altering the voltage dependencies of several voltage-gated ion
channels. These findings can form the basis for a new pharmacological strategy to
treat atrial fibrillation.
PMID- 28514016
TI - Self-Adjusting, Polymeric Multilayered Roll that can Keep the Shapes of the Blood
Vessel Scaffolds during Biodegradation.
AB - A self-adjusting, blood vessel-mimicking, multilayered tubular structure with two
polymers, poly(epsilon-caprolactone) (PCL) and poly(dl-lactide-co-glycolide)
(PLGA), can keep the shape of the scaffold during biodegradation. The inner (PCL)
layer of the tube can expand whereas the outer (PLGA) layers will shrink to
maintain the stability of the shape and the inner space of the tubular shape both
in vitro and in vivo over months. This approach can be generally useful for
making scaffolds that require the maintenance of a defined shape, based on FDA
approved materials.
PMID- 28514018
TI - Salvage of postcranioplasty implant exposure using free tissue transfer.
AB - BACKGROUND: Refractory implant exposure is frustrating after cranioplasty. The
purpose of this study was for the authors to present their experience with free
tissue transfer for salvage of postcranioplasty implant exposure. METHODS: A
retrospective medical chart review was conducted on all free tissue transfers
performed for exposed implant coverage after cranioplasty between January 2004
and February 2016. RESULTS: Twelve free flaps were performed in 11 patients who
underwent postcranioplasty with implant exposure, and whose attempted implant
coverage using locoregional flaps had failed. The free flaps used included
anterolateral thigh flap, radial forearm flap, anteromedial thigh and rectus
femoris chimeric flap, latissimus dorsi flap, gracilis flap, and Juri flap. The
flap survival rate was 100%, and 10 of 11 implants (91%) were salvaged without
removal. CONCLUSIONS: Free tissue transfer should be considered as the preferred
reconstructive option for postcranioplasty exposed implant salvage. High rate of
implant salvage (>90%) is possible even with chronic implant exposure (>3
months).
PMID- 28514020
TI - Work-related stress factors and problem drinking with special reference to
measures of drinking.
PMID- 28514019
TI - Does dust-associated pulmonary alveolar proteinosis represent an autoimmune
disorder?
AB - The role of autoantibodies against granulocyte-macrophage colony-stimulating
factor (GM-CSF) in the development of secondary pulmonary alveolar proteinosis
(PAP) in patients exposed to occupational and environmental dust remains unclear.
Herein, we describe two cases of secondary PAP who had GM-CSF antibodies and
absence of STAT5 phosphorylation index, suggestive of a potential relationship
between the appearance of GM-CSF antibodies and environmental dust exposure.
However, whether the presence of GM-CSF antibodies is a part of the pathological
process or represents an epiphenomenon is currently unknown. In this report, we
would like to present two cases supporting these new data and briefly discuss the
possible role of autoimmune mechanisms in the development of secondary PAP. Am.
J. Ind. Med. 60:591-597, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28514022
TI - One-year weight change and long-term sickness absence in professional
firefighters.
AB - BACKGROUND: Little is known about the association between weight change
(particularly moderate weight loss, 5-10% in initial weight) and long-term
sickness absence (LSA) in working populations. METHODS: Three hundred and forty
professional firefighters reported their current and past (1 year ago) weights in
a cross-sectional survey, along with their LSA experience due to a severe
accident, injury, or illness during the previous 12 months. RESULTS: The
prevalence of LSA was 14.7%. In the non-smoking male firefighters, the prevalence
of LSA was 3.4% in those with moderate weight loss over the past year; 13.3% in
those who maintained their weight; and 21.7% in those who gained their weight
moderately: gamma coefficient, 0.44 (95%CI: 0.05, 0.66). The linear association
remained significant after further controlling for age and alcohol consumption.
And it was similar across the adiposity strata (normal weight, overweight, and
obesity) of the firefighters 1 year ago. CONCLUSIONS: One-year weight loss was
associated with decreased risk of LSA in professional firefighters.
PMID- 28514021
TI - An update systematic review of fetal death, congenital anomalies, and fertility
disorders among health care workers.
AB - BACKGROUND: Health care workers (HCWs) are occupationally exposed to various
hazards, some associated with adverse pregnancy outcomes in previous reviews.
This systematic review aims at synthesizing the recent literature on occupational
exposures among HCWs related to fetal death, congenital anomalies, and fertility
disorders. METHODS: We searched the Medline database from 2000 to 2015 for
articles about all potential occupational exposures of women and men working in
this sector. RESULTS: We retained 32 studies, most of them (n = 30) among women
HCWs. Studies based on job title reported excess risks of some congenital
anomalies (especially nervous and musculoskeletal systems) among HCWs compared to
non-HCWs but no evidence about fetal death. Excess risks associated with specific
exposures includes reports of some congenital anomalies for women exposed to
anesthetic gases. Exposure to some sterilizing agents and, with less evidence, to
antineoplastic drugs and to ionizing radiation, is associated with increased
risks of miscarriage but not stillbirth. Strenuous work schedules appear to be
associated with fertility disorders, but the evidence is limited. Only a few
studies have been published since 2000 about non-ionizing radiation, or about
fertility disorders related to chemical or physical agents, or about male HCWs.
CONCLUSIONS: Despite the establishment of recommendations to limit exposures of
HCWs, some excess risks of adverse pregnancy outcomes are still reported and need
to be explained.
PMID- 28514023
TI - Silicosis prevalence and risk factors in semi-precious stone mining in Brazil.
AB - BACKGROUND: Underground mining generates large amounts of dust and exposes
workers to silica. This study aims to determine the prevalence and predictor
factors for the development of silicosis among semi-precious-stone mineworkers in
southern Brazil working in a self-administered cooperative. METHODS: In a cross
sectional study of 348 current workers and retirees, demographic data, medical,
and occupational history were collected through an interview performed by a nurse
and medical record review. Risk factor associations were studied by Poisson
multivariate regression. RESULTS: The overall prevalence of silicosis was 37%,
while in current miners it was 28%. Several risk factors for silicosis were
identified in the univariate analysis. Inadequate ventilation in the underground
galleries combined with dry drilling, duration of silica exposure, and
(inversely) education remained significant in the multivariate analysis (P <
0.05). CONCLUSION: This study is unusual in studying semi-precious stone
mineworkers in a self-administered worker cooperative with limited resources. The
prevalence of silicosis was very high. A number of recommendations are made
including technical support for worker cooperatives, surveillance of silica
exposure and silicosis, exposure reduction measures, and benefits allowing
impaired miners to leave the industry.
PMID- 28514024
TI - Historical review of efforts to reduce noise-induced hearing loss in the United
States.
AB - BACKGROUND: Noise-induced hearing loss is a centuries-old problem that is still
prevalent in the United States and worldwide. AIM: To describe highlights in the
development of hearing loss prevention in the U.S. from World War II to the
present. METHODS: Literature review. RESULTS: Approaches to occupational noise
induced hearing loss prevention in the United States over the past seven decades
are described using a hierarchy of controls framework and an interdisciplinary
perspective. Historical timelines and developmental milestones related to
occupational noise-induced hearing loss prevention are summarized as a life
course. DISCUSSION: Lessons are drawn for other countries in their hearing
conservation efforts. CONCLUSION: Future developments building on the hearing
loss prevention work of the past 70 years can prevent the problem of occupational
NIHL in the 21st century. Am. J. Ind. Med. 60:569-577, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28514026
TI - Gambling with life: Masculinity, risk, and danger in the lives of unauthorized
migrant roofers.
AB - BACKGROUND: This paper examines the occupational experiences of unauthorized
immigrants employed in one of the most dangerous occupations in the United
States: roofing. METHODS: We draw on 40 in-depth interviews with return migrants
in Guanajuato, Mexico, to examine how the adoption of masculinity, dangerous
working conditions, the labor market structure, and absence of legal status
exacerbates injuries for unauthorized roofers. FINDINGS: Undocumented men return
to Mexico injured with chronic pain, health complications, and trauma. We find
that men "do gender" that is adopt masculine beliefs, when they skirt safety
practices, police each other's behaviors, withhold their emotions, experience
heightened stress, and engage in poor health behaviors. It is a combination of
dangerous working conditions, economic insecurity, and men seeking to fulfill
their masculine roles that all combine to create unsafe working conditions and
lead to injuries.
PMID- 28514027
TI - Maximum oxygen consumption in marginally malnourished Colombian boys and girls 6
16 years of age.
AB - Treadmill measurements of maximum oxygen intake were made in 218 boys and 136
girls 6-16 years of age who were classified as nutritionally normal or marginally
malnourished. max (1. min-1 )increased with age, was lower in the undernourished
than in the normal, and was significantly lower in girls than in boys. The sex
differences persisted when max was expressed in terms of body weight and lean
body mass, indicating that differences in physical activity between sexes may be
the cause. The lower values of absolute max have implications for the productive
ability of these children in heavy physical work when they are adults. When
expressed in terms of body weight there are no major differences between
Colombian and European children in the magnitude of their max values.
PMID- 28514025
TI - Acute joint pain in the emerging green collar workforce: Evidence from the linked
National Health Interview Survey and Occupational Information Network (O*NET).
AB - BACKGROUND: Green jobs are a rapidly emerging category of very heterogeneous
occupations that typically involve engagement with new technologies and changing
job demands predisposing them to physical stressors that may contribute to the
development of joint pain. METHODS: We estimated and compared the prevalence of
self-reported acute (past 30 days) joint pain between green and non-green collar
workers using pooled 2004-2012 National Health Interview Survey (NHIS) data
linked to the Occupational Information Network Database (O*NET). RESULTS: Green
collar workers have a higher prevalence of acute joint pain as compared to non
green collar workers. Green collar workers with pain in the upper extremity
joints were significantly greater than in the non-green collar workforce, for
example, right shoulder [23.2% vs 21.1%], right elbow [13.7% vs 12.0%], left
shoulder [20.1% vs 18.2%], and left elbow [12.0% vs 10.7%]. CONCLUSIONS: Acute
joint pain reported by the emerging green collar workforce can assist in
identifying at risk worker subgroups for musculoskeletal pain interventions.
PMID- 28514028
TI - Clustering of cardiovascular risk factors in association with indices of
adiposity and adipose tissue distribution in adults.
AB - The hypothesis, that clustering of elevated levels of blood pressures, plasma
lipids and lipoprotein cholesterols, and serum glucose in men and women was
associated with indices of adiposity and adipose tissue distributione was tested
while controlling for family membership, age, level of education, income, and
smoking as well as menopause (surgical and natural )and the use of oral
contraceptives and replacement estrogens in women. The study population included
146 white men and 171 white women, 18-88 years of age, from 4 large kindreds
residing in the Dayton, Ohio, metropolitan area. The data were collected between
1977 and 1980 as part of a study of genetic factors in essentials hypertension.
Four groups of individuals with similar levels for blood pressures, plasma lipids
and lipoprotein cholesterols, and serum glucose were defined for each sex by
using a k-means clustering algorithm. A group was identified in each sex that had
higher than average values for all of these risk factors. Membership in this
group was associated significantly with age and weight/stature2 in the men, and
with age, weight/stature2 and the interaction of age and weight/stature2 in the
women, after controlling for level of education, income, smoking, and, in the
women, also for menopause, use of oral contraceptives, and replacement estrogens.
Group membership was not associated significantly with family membership or with
an index of adipose tissue distribution.
PMID- 28514030
TI - Program of the 13th annual meeting of the Human Biology Council San Diego,
California, April 4-6, 1989.
PMID- 28514029
TI - Population decline in a Philippine Negrito hunter-gatherer society.
AB - The Casiguran Agta constitute a Negrito hunter-gatherer society in northeastern
Luzon. The hypothesis presented is that this population has suffered serious
decline over the last half -century. Demographic data collected over a 24-year
period are used to substantiate this hypothesis. Agta figures on crude death
rate, rate of natural decrease, infant mortality, life expectancy at birth, and
homicide are among the most extreme known for any human population. Reasons for
this decline are described, with emphasis on the factor of homicide.
PMID- 28514031
TI - Bylaws of the Human Biology Council.
PMID- 28514032
TI - Longitudinal growth in height, weight, and bone age of Guatemalan Ladino and
Indian schoolchildren.
AB - Three longitudinal samples of Guatemalan schoolchildren are compared for amounts
and rates of growth in height, weight, and bone age. The samples include children
of two ethnic backgrounds: Ladinos, Spanish-speaking people of, generally,
Western cultural orientation; and Indians, people of Mayan cultural descent. The
Indians are of very low socioeconomic status (SES) and attend a public school in
a rural village. The Ladinos come from two SES groups living in Guatemala City,
one of high SES attending a private school and the other of low SES attending a
public school. Graphical and statistical analyses show that for all samples of
boys and girls there are generally, significant differences between samples (high
SES>low SES>Indian) for amounts of growth in height, weight, and bone age. Boys
show significant differences in rates of growth between samples, with the high
SES sample growing more rapidly than the two low SES samples. Girls show
significant differences in the rate of growth in height, but not in the rate of
growth in weight or bone age. For Both boys and girls, rates of growth in height
and weight differ more between samples than does rate of Skeltal development.
These results demonstrate that (1) SES-related deficits in growth are cumulative
during childhood and early adolescence, that (2) rates of growth for boys are,
generally, more sensitive to the influence of SES than are the growth rates of
girls, and that (3) childhood growth deficits of low SES children of low SES
children are likely to carry over into adulthood.
PMID- 28514033
TI - Implementation of Hills' growth curve analysis for unequal-time intervals using
GAUSS.
AB - Longitudinal data are widely regarded as the most efficient and informative type
of data with which to investigate growth. Paradoxically, appropriate statistical
methods for analyzing longitudinal data have been unavailable; with the exception
of a computer program for executing Rao's (Biometrika 46:49-58, 1959) one-sample
polynomial growth curve analysis (Schneiderman and Kowalski, Am. J. Phys.
Anthropol. 67:323-333, 1985) and another applying the Preece-Baines function
(Brown and Townsend, Ann. Hum. Biol. 9:495-505, 1982), no programs for analyzing
longitudinal data are generally available to the scientific community. Whereas
much of the pediatrically oriented work has involved fitting growth curves for
individual children, the concern here is the estimation of growth trends for
populations. An Adequate understanding of average tendencies is a prerequisite to
understanding the growth of individuals. The present paper implements Hills'
(Biometrics 24:189-196, 1968) analysis, which is formally equivalent to Rao's but
uses finite differences instead of orthogonal polynomials. This method is
suitable for data collected at unequal time points and generates explicit
measures of velocity and acceleration. The polynomial specification of the curve
that best fits the data is also determined with this method. An additional
advantage of this approach is that it is conceptually simpler than the classic
model of Rao. An application of this method is given using the same craniofacial
growth data as in our earlier (1985) paper for comparability. We provide an easy
to use program written in GAU's (Edlefson and Jones, Kent, WA; Applied Technical
Systems, 1985), a matrix programming language that runs on PC-compatible
microcomputers. This implementation for PCs extends the accessibility to
investigators who may not have access to mainframe computers.
PMID- 28514034
TI - Environmental influences cause menstrual synchrony, not pheromones.
AB - To assess the influence of environmental conditions on the pattern of menstrual
variation among women, data on menstrual cycles were recorded longitudinally from
127 university women who lived in a group of houses surrounding a central
courtyard. Adequate follow-up was available on 76 women, among whom menstrual
synchrony occurred in a short period of time. During the first month of
coresidence, the day of menstrual onset deviated from the mean by an average of
13.7 days. During the next month, however, this average deviation declined to
2.6days. Moreover, it was found that menstrual synchrony occurred in the overall
sample regardless of the house of residence, although synchrony occurred to a
greater extent in some houses than in others. It would thus appear that common
environmental influences play an important role in the overall pattern of
menstrual cyclicity.
PMID- 28514035
TI - American Journal of Human Biology as the new official publication of the Human
Biology Council.
PMID- 28514036
TI - Validity of anthropometric regression equations for predicting changes in body
fat of obese females.
AB - The validity of ten popular anthropometric percent fat prediction equations for
estimating changes in percentage of body fat for obese females was studied.
Thirty-one obese females (mean +/- SEM, %fat = 36.7 +/- 1.1%, body mass = 75.6 +/
1.7 kg, age = 32.8 +/- 1.1 years) participated in a diet-only, diet-plus
exercise, or exercise-only program. Subjects lost 2.7 +/- 0.3 fat percentage
points and 3.0 +/- 0.3 kg body mass during the 8-week study. While many of the
equations had acceptable validity before and after body mass loss, when applied
to the prediction of changes in body fat none of the equations was acceptable. It
was concluded that use of anthropometric prediction equations to estimate
individual percent fat change scores results in large errors and is not
recommended.
PMID- 28514037
TI - Socioeconomic correlates of fertility, mortality, and child survival in mothers
from a disadvantaged, urban Guatemalan community.
AB - Social and economic determinants of fertility, mortality, and child survival were
studied in a sample of 519 mothers from EL Progreso, a disadvantaged community
located on the outskirts of Guatemala city. Fertility (children ever-born) and
mortality (number of children who had died postnatally) data were obtained from
interviews, along with data on the characteristics of the mothers, fathers, and
the households. Contraceptive use was recorded on a subsample of 167 mothers of 5
year old children. Following factor analyses, three variables were selected for
analysis: Years of schooling of the father and the mother and the type of fuel
used for cooking. Father's education and type of fuel were significantly related
to maternal fertility, while only the educational attainment of the mother was
related to child mortality and survival. When contraceptive use was included in
the ANCOVA in the subsample, it was a significant determinant of fertility, while
father's education became nonsignificant. In terms of mortality, contraceptive
use was a significant determinant, while the significance of the mother's
education fell to a borderline value (P = 0.084).
PMID- 28514038
TI - Editorial.
PMID- 28514039
TI - Sexual maturation of Mexican-American adolescents.
PMID- 28514040
TI - Salivary testosterone levels in males from the Ituri Forest of Zaire.
AB - Morning and evening testosterone levels were measured in the saliva of Efe
pygmies (N = 11) and Lese villagers (N = 18) living in the Ituri Forest of
northeast Zaire and compared with levels in Boston controls (N = 10). With one
exception, levels in the individual Zairois subjects fall within the normal
ranges reported for Western clinical populations. Daily variation in the Zairois
subjects (a.m./p.m. ratio = 1.32 for Efe, 1.22 for Lese) is also comparable to
both the Boston controls (1.61) and values reported by other researchers for
Western subjects. Average morning levels for the Zairois subjects (420 pmol/liter
for Efe, 341 pmol/liter for Lese), however, fall significantly below the average
for the Boston subjects (589 pmol/liter; Efe, P <0.05; Lese, P <0.01). A
correlation between morning testosterone level and height is observed for the
Lese sample (r=0.76, P <0.005). Similar correlations have not been reported for
Western subjects. Possible roles of acute and chronic environmental conditions in
generating these observations are noted. This study demonstrates the potential
utility of salivary steroid assays for investigating questions related to male
gonadal function under field conditions.
PMID- 28514041
TI - Gynoid and android fat patterning in Japanese-American men: Body build and
glucose metabolism.
AB - Subcutaneous fat patterning was investigated in a sample of 229 second generation
(Nisei) Japanese-American men enrolled in an epidemiological study of noninsulin
dependent diabetes mellitus. The study sample consisted of 78 men with diabetes,
72 with impaired glucose tolerance (IGT), and 79 with normal glucose tolerance,
classified by a 75 gm oral glucose tolerance test(OGTT) and world Health
Organization criteria. A combination of hierarchal cluster analysis and
logarithmic regression analysis using skinfold thickness at seven anatomical
sites yielded two distinctive fat pattern groups, viz, a gynoid fat pattern group
(n = 16), with a significantly greater percentage of fat on the extremities; and
an exaggerated android group (n = 34), with proportionately more fat on the trunk
than predicted from total skinfold fat thickness. The two fat pattern groups and
a sample of men of normal glucose tolerance (n = 53) were compared by analysis of
variance with respect to 12 somatometric variables and indices encompassing
length, breadth and muscle mass parameters. The three groups did not differ in
age or height. In weight and body mass index, the gynoid fat pattern group was
lowest, although there were no significant intergroup differences in total
skinfold fat (seven sites summed). The gynoid group was also significantly less
robust in body build than the android group, as judged by a lower intermembral
index, lower ratios of bony chest breadth and biacromial diameter to sitting
height, and reduced arm muscle mass. The prevalence of diabetes within each fat
pattern group was slightly less than expected on the basis of the prevalence of
IGT (44%) was found within the gynoid group; none of the differences were
statistically significant. During the OGTT, the gynoid and android groups, minus
diabetic men, differed significantly from men with normal glucose tolerance in
serum glucose levels at 1.5 and 2 hr but not from one another. The limitations of
cross-sectional data of this nature for determining a differential risk
fordisorders of glucose metabolism associated with type of fat deposition are
discussed.
PMID- 28514042
TI - Effect of Crystallization Firing on Marginal Gap of CAD/CAM Fabricated Lithium
Disilicate Crowns.
AB - PURPOSE: To evaluate the marginal gaps of CAD/CAM (CEREC 3) produced crowns made
from leucite-reinforced glass-ceramic (IPS Empress CAD) blocks (LG), and lithium
disilicate (IPS e.max CAD) blocks before (LD-B), and after (LD-A) crystallization
firing. MATERIALS AND METHODS: A human molar tooth (#19) was mounted with
adjacent teeth on a typodont and prepared for a full-coverage ceramic crown. The
typodont was assembled in the mannequin head to simulate clinical conditions.
After tooth preparation 15 individual optical impressions were taken by the same
operator using titanium dioxide powder and a CEREC 3 camera per manufacturer's
instructions. One operator designed and machined the crowns in leucite-reinforced
glass-ceramic blocks (n = 5) and lithium-disilicate blocks (n = 10) using the
CEREC 3 system. The crowns were rigidly seated on the prepared tooth, and
marginal gaps (MUm) were measured with an optical microscope (500*) at 12 points,
3 on each of the M, B, D, and L surfaces of the leucite-reinforced glass-ceramic
crowns and the lithium-disilicate crowns before and after crystallization firing.
Results were analyzed by two-way ANOVA followed by a Tukey's post hoc multiple
comparison test (alpha = 0.05). RESULTS: The overall mean marginal gaps (MUm) for
the crowns evaluated were: LG = 49.2 +/- 5.5, LD-B = 42.9 +/- 12.2, and LD-A =
57.2 +/- 16.0. The marginal gaps for LG and LD-B were not significantly
different, but both were significantly less than for LD-A. CONCLUSIONS: The type
of ceramic material did not affect the marginal gap of CAD/CAM crowns. The
crystallization firing process required for lithium-disilicate crowns resulted in
a significant increase in marginal gap size, likely due to shrinkage of the
ceramic during the crystallization process. CLINICAL RELEVANCE: The marginal gap
of CAD/CAM-fabricated lithium disilicate crowns increases following
crystallization firing. The marginal gap still remains within clinically
acceptable parameters.
PMID- 28514043
TI - Factors affecting a face-to-face learning event.
AB - BACKGROUND: Pharmacy professionals have multiple opportunities to attend learning
events run by a series of providers. However, there has never been a large-scale
evaluation of events. Currently, formats of learning sessions differ by provider
with no optimum model identified. Pharmacy Education South London was formed in
April 2014 for the provision of education and training for pharmacy professionals
in South London, running sessions multiple times across various locations.
OBJECTIVE: The objective of this work was to identify factors that influence the
perceived success of a face-to-face supplementary education and training event
from the perspective of attendees. METHODS: Evaluation forms from 600
participants at training events followed by semi-structured individual interviews
with 11 participants. KEY FINDINGS: Participants over 55 years were more likely
to attend lecture style events versus those aged under 25 years who attended more
workshops (P < 0.001); there was no correlation with gender. About 57.3% (n =
344) of participants agreed fully that the event increased their understanding of
the topics, although only 38.5% (n = 231) stated that it would change their
practice. Themes influencing an event fell into three broad themes: personal
reasons affecting attendance, success factors for the session and application of
learning, all with related subthemes. Subthemes included commitments,
convenience, awareness, topic and personal relevance, content and delivery and
reference, review and action. CONCLUSIONS: In publicising events, the topic,
including the driver for the topic and the skills that will be obtained, the
speaker and their experience plus how learning can be applied after the event
should be included.
PMID- 28514044
TI - Specific Identification of Glycoproteins Bearing the Tn Antigen in Human Cells.
AB - Glycoproteins contain a wealth of valuable information regarding the development
and disease status of cells. In cancer cells, some glycans (such as the Tn
antigen) are highly up-regulated, but this remains largely unknown for
glycoproteins with a particular glycan. Herein, an innovative method combining
enzymatic and chemical reactions was first designed to enrich glycoproteins with
the Tn antigen. Using synthetic glycopeptides with O-GalNAc (the Tn antigen) or O
GlcNAc, we demonstrated that the method is selective for glycopeptides with O
GalNAc and can distinguish between these two modifications. The diagnostic ions
from the tagged O-GalNAc further confirmed the effectiveness of the method and
confidence in the identification of glycopeptides with the Tn antigen by mass
spectrometry. Using this method, we identified 96 glycoproteins with the Tn
antigen in Jurkat cells. The method can be extensively applied in biological and
biomedical research.
PMID- 28514046
TI - Systematic review: Early infant feeding practices and the risk of wheat allergy.
AB - AIM: Wheat is a common allergen. Early feeding practices (breastfeeding,
potentially allergenic foods) might affect the risk of allergy. To systematically
evaluate the association between early feeding practices and the risk of wheat
allergy and sensitisation. METHODS: Five databases were searched for studies of
any design up to July 2015. RESULTS: We included seven studies (five
observational, low to moderate quality, two randomised controlled trials (RCTs),
high quality). The results come from observational studies unless stated
otherwise. Longer breastfeeding was associated with wheat allergy (two studies, n
= 1847) and sensitisation (one study, n = 3781). Evidence for exclusive
breastfeeding was contradictory; longer exclusive breastfeeding was associated
with either lower (one study, n = 408) or higher (one study, n = 3781) risk of
wheat sensitisation. Breastfeeding at gluten introduction did not affect the risk
of wheat allergy (two studies, n = 2581). Introducing cereal >=7 months of age
increased the risk of wheat allergy (one study, n = 1612), but results from an
RCT (n = 1303) showed no effect. Early introduction of gluten was associated with
a reduced risk of wheat sensitisation up to 5 years in one observational study (n
= 3781) but not in RCTs (n = 1303). CONCLUSIONS: Based on limited evidence, the
influence of breastfeeding and an early exposure to gluten on the risk of wheat
allergy remain uncertain. There is no evidence supporting breastfeeding at gluten
introduction as modifying the risk. Early introduction of gluten might reduce the
risk of sensitisation, but currently, no evidence exists that it affects the risk
of wheat allergy.
PMID- 28514047
TI - A Simplified Approach for Fabrication of a Lightweight Individualized Impression
Tray with the Aid of Existing Obturator Prosthesis Using Lost Salt Technique.
AB - Maxillary defects resulting from ablative oncologic surgery can be extensive and
usually have complex contours. Impression procedures for such defects can be time
consuming and cumbersome, challenging the skills of even the most-experienced
clinician. A well-oriented impression tray with proper extension and adequate
contour is essential for successfully capturing the relevant details in
impression. This article describes a method using the patient's existing
obturator prosthesis to simplify and expedite the fabrication of a lightweight
individualized impression tray directly on an irreversible hydrocolloid
impression, thus avoiding the preliminary impression procedure for the patient.
PMID- 28514045
TI - Contrast Extravasation versus Hemorrhage after Thrombectomy in Patients with
Acute Stroke.
AB - BACKGROUND AND PURPOSE: Intra-arterial recanalization postprocedural imaging in
stroke patients can result in diagnostic complications due to hyperdensities on
noncontrast computed tomography (CT), which may represent either contrast
extravasation or intracranial hemorrhage. If these lesions are hemorrhage, then
they are risk factors becoming symptomatic, which, if not distinguished, can
alter clinical management. We investigate the effects of iodinated contrast on
postprocedural magnetic resonance imaging (MRI) and prevalence of equivocal
imaging interpretations of postprocedural extravasated contrast versus hemorrhage
while identifying protocol pitfalls. METHODS: We identified 10 patients diagnosed
with ischemic stroke who underwent intra-arterial recanalization in a 5-year
period. These patients demonstrated a hyperdensity on a postprocedural CT within
24 hours, underwent an MRI within 48 hours, and an additional confirmatory
noncontrast CT at least 72 hours postprocedure. RESULTS: Postprocedural MRI in
all 10 stroke patients demonstrated T1 - and T2 -relaxation time changes due to
residual iodine contrast agents. This lead to false positive postprocedural
hemorrhage MRI interpretations in 2/10 patients, 3/10 false negative
interpretations of contrast extravasation, and 5/10 equivocal interpretations
suggesting extravasation or hemorrhage. Of these five cases, two were performed
with gadolinium. CONCLUSION: MRI done within 48 hours postprocedure can lead to
false positive hemorrhage or false negative contrast extravasation
interpretations in stroke patients possibly due to effects from the administered
angiographic contrast. Additionally, MRI should be done both after 72 hours for
confirmation and without gadolinium contrast as the effects of the gadolinium
contrast and residual angiographic contrast could lead to misdiagnosis.
PMID- 28514048
TI - Carbon-Doped BN Nanosheets for the Oxidative Dehydrogenation of Ethylbenzene.
AB - Carbon-based catalysts have demonstrated great potential for the aerobic
oxidative dehydrogenation reaction (ODH). However, its widespread application is
retarded by the unavoidable deactivation owing to the appearance of coking or
combustion under ODH conditions. The synthesis and characterization of porous
structure of BCN nanosheets as well as their application as a novel catalyst for
ODH is reported. Such BCN nanosheets consist of hybridized, randomly distributed
domains of h-BN and C phases, where C, B, and N were confirmed to covalent bond
in the graphene-like layers. Our studies reveal that BCN exhibits both high
activity and selectivity in oxidative dehydrogenation of ethylbenzene to styrene,
as well as excellent oxidation resistance. The discovery of such a simple
chemical process to synthesize highly active BCN allows the possibility of
carbocatalysis to be explored.
PMID- 28514050
TI - Photoredox-Controlled Mono- and Di-Multifluoroarylation of C(sp3 )-H Bonds with
Aryl Fluorides.
AB - A controllable mono- and di-multifluoroarylation of acyclic and cyclic N-aryl
amines with aryl fluorides by photocatalyzed dual C(sp3 )-H/C(sp2 )-F
functionalization has been developed, providing new access to a wide array of
valuable alpha-fluoroarylated amines. In addition, the one-pot consecutive hetero
di-multifluoroarylation of N-aryl pyrrolidines and N,N-dimethylanilines was
achieved with high to excellent diastereoselectivity. This new defluorinative
C(sp3 )-C(sp2 ) coupling is distinguished by a broad scope, good
regioselectivity, and mild conditions as well as gram-scale and late-stage
applicability, and thus constitutes a significant advance in the arylation of
unactivated C(sp3 )-H bonds with aryl fluorides.
PMID- 28514049
TI - Canine Cutaneous Plasmacytosis: 21 Cases (2005-2015).
AB - BACKGROUND: Cutaneous plasmacytosis (CP) is a syndrome of multiple cutaneous
plasma cell tumors, in the absence of multiple myeloma. Although rare in both
humans and dogs, treatment recommendations are usually extrapolated from multiple
myeloma protocols. To date, no case series of CP have been described in the
veterinary literature. HYPOTHESIS/OBJECTIVES: To describe clinical presentation,
determine treatment response rates and duration, and report overall survival of
dogs with CP. ANIMALS: Twenty-one client-owned dogs with CP. METHODS: Medical
records of 21 dogs with CP were reviewed. Diagnosis was based on histopathologic
evaluation of at least 1 representative cutaneous or subcutaneous lesion in dogs
with >=3 lesions. Dogs with suspicion of multiple myeloma were excluded. RESULTS:
The most commonly affected breeds were the golden (5/21) and Labrador retriever
(3/21). Fourteen of 21 dogs had >10 lesions, with some having >100. Lesions
commonly were described as round, raised, pink-to-red, and variably alopecic or
ulcerated. The most commonly used drug protocol was combined melphalan and
prednisone, with an overall response rate (ORR) of 73.7% (14/19 dogs). Single
agent lomustine was associated with a similar ORR of 71.4% (5/7 dogs). For all
treatments combined, the median progression-free interval after the first
treatment was 153 days. The median survival time from the first treatment was 542
days. CONCLUSIONS AND CLINICAL IMPORTANCE: Alkylating agents were effective in
inducing remission of CP; corticosteroids, melphalan, and lomustine were the most
commonly used drugs. Survival times were similar to those reported in dogs with
multiple myeloma treated with alkylating agents.
PMID- 28514052
TI - Shift in community structure in an early-successional Mediterranean shrubland
driven by long-term experimental warming and drought and natural extreme
droughts.
AB - Global warming and recurring drought are expected to accelerate water limitation
for plant communities in semiarid Mediterranean ecosystems and produce
directional shifts in structure and composition that are not easily detected, and
supporting evidence is scarce. We conducted a long-term (17 years) nocturnal
warming (+0.6 degrees C) and drought (-40% rainfall) experiments in an early
successional Mediterranean shrubland to study the changes in community structure
and composition, contrasting functional groups and dominant species, and the
superimposed effects of natural extreme drought. Species richness decreased in
both the warming and drought treatments. Responses to the moderate warming were
associated with decreases in herb abundance, and responses to the drought were
associated with decreases in both herb and shrub abundances. The drought also
significantly decreased community diversity and evenness. Changes in abundance
differed between herbs (decreases) and shrubs (increases or no changes). Both
warming and drought, especially drought, increased the relative species richness
and abundance of shrubs, favoring the establishment of shrubs. Both warming and
drought produced significant shifts in plant community composition. Experimental
warming shifted the community composition from Erica multiflora toward Rosmarinus
officinalis, and drought consistently shifted the composition toward Globularia
alypum. The responses in biodiversity (e.g., community biodiversity, changes of
functional groups and compositional shifts) were also strongly correlated with
atmospheric drought (SPEI) in winter-spring and/or summer, indicating sensitivity
to water limitation in this early-successional Mediterranean ecosystem,
especially to natural extreme droughts. Our results suggest that the shifts in
species assembles and community diversity and composition are accelerated by the
long-term nocturnal-warming and drought, combined with natural severe droughts,
and that the magnitude of the impacts of climate change is also correlated with
the successional status of ecosystem. The results thus highlight the necessity
for assessing the impacts on ecosystemic functioning and services and developing
effective measures for conserving biodiversity.
PMID- 28514053
TI - A cluster randomized theory-guided oral hygiene trial in adolescents-A latent
growth model.
AB - OBJECTIVES: (i) To test whether theory-guided interventions are more effective
than conventional dental instruction (CDI) for changing oral hygiene in
adolescents and (ii) to examine whether such interventions equally benefit both
genders and different socio-economic (SES) groups. METHODS: A total of 244
adolescents were recruited from three schools, and cluster randomization
allocated adolescents to one of the three types of interventions: two were theory
based interventions (Precaution Adoption Process Model or Authoritative Parenting
Model) and CDI served as an active control. Oral hygiene levels % (OH) were
assessed at baseline, after 3 months and after 12 months. RESULTS: A complete
data set was available for 166 adolescents (the total follow-up rate: 69%). There
were no significant differences in baseline OH between those who participated
throughout the study and those who dropped out. Bivariate and multivariate
analyses showed that theory-guided interventions produced significant
improvements in oral hygiene and that there were no significant gender or socio
economic differences. CONCLUSIONS: Theory-guided interventions produced more
positive changes in OH than CDI, and these changes did not differ between gender
and SES groups.
PMID- 28514051
TI - The PPARgamma-SETD8 axis constitutes an epigenetic, p53-independent checkpoint on
p21-mediated cellular senescence.
AB - Cellular senescence is a permanent proliferative arrest triggered by genome
instability or aberrant growth stresses, acting as a protective or even tumor
suppressive mechanism. While several key aspects of gene regulation have been
known to program this cessation of cell growth, the involvement of the epigenetic
regulation has just emerged but remains largely unresolved. Using a systems
approach that is based on targeted gene profiling, we uncovered known and novel
chromatin modifiers with putative link to the senescent state of the cells. Among
these, we identified SETD8 as a new target as well as a key regulator of the
cellular senescence signaling. Knockdown of SETD8 triggered senescence induction
in proliferative culture, irrespectively of the p53 status of the cells; ectopic
expression of this epigenetic writer alleviated the extent doxorubicin-induced
cellular senescence. This repressive effect of SETD8 in senescence was mediated
by directly maintaining the silencing mark H4K20me1 at the locus of the
senescence switch gene p21. Further in support of this regulatory link, depletion
of p21 reversed this SETD8-mediated cellular senescence. Additionally, we found
that PPARgamma acts upstream and regulates SETD8 expression in proliferating
cells. Downregulation of PPARgamma coincided with the senescence induction, while
its activation inhibited the progression of this process. Viewed together, our
findings delineated a new epigenetic pathway through which the PPARgamma-SETD8
axis directly silences p21 expression and consequently impinges on its senescence
inducing function. This implies that SETD8 may be part of a cell proliferation
checkpoint mechanism and has important implications in antitumor therapeutics.
PMID- 28514054
TI - How do educators in one New Zealand undergraduate Bachelor of Oral Health course
teach and nurture professionalism?
AB - INTRODUCTION: Research on integrated dental hygiene and dental therapy courses is
scarce; studies reporting on how staff in these combined scope courses teach
professionalism are even more scarce. This study aimed to partially fill these
research gaps. METHOD AND MATERIALS: In 2016, online surveys were sent to 34
staff members who taught into the integrated Bachelor of Oral Health (BOH) course
at the University of Otago's Faculty of Dentistry; 13 were returned. Two focus
groups were conducted with six BOH educators. RESULTS: Aspects of professionalism
were taught and nurtured in the formal curriculum, the clinic and the informal
curriculum. In the formal curriculum, policies outlining the professional
standards of behaviour expected of oral health practitioners and students in New
Zealand and the Faculty were discussed. In the clinic, educators taught
professionalism through modelling clinical skills, assessing students'
performance and commenting on their reflective logbooks. In the informal
curriculum, BOH teachers nurtured professionalism through discussions about
standards of behaviour outside of the university. Role modelling was the most
common method that participants reported they taught or nurtured professionalism
in their students. DISCUSSION: Professionalism is a complex concept that is
taught and nurtured in a number of ways over all aspects of the course.
CONCLUSION: Oral Health educators need to maintain a high standard of
professionalism when interacting with students and patients, as well as in public
spaces, in order to model professionalism to their students.
PMID- 28514056
TI - Ulcerative plaque within a tattoo in a 49-year-old man.
PMID- 28514057
TI - High-performance liquid chromatographic cartridge with gradient elution
capability coupled with UV absorbance detector and mass spectrometer for peptide
and protein analysis.
AB - We discuss the construction and performance of a high-performance liquid
chromatography cartridge that we developed that resulted from a culmination of
previous research. We have recently developed an innovative approach to creating
gradient elutions using dual electroosmotic pumps and a series of three valves.
This method has been proved to be the most reproducible and robust in producing
gradients compared to our previously tested methods. Using this approach, we have
assembled a high-performance liquid chromatography cartridge powered and
controlled via a computer. We have successfully coupled the cartridge with an
ultraviolet absorbance detector and a mass spectrometer for separating complex
protein/peptide samples. The cartridge is readily coupled with other detectors
such as electrochemical detector and laser-induced fluorescence detector.
PMID- 28514055
TI - Caveolin-1 deficiency induces premature senescence with mitochondrial
dysfunction.
AB - Paradoxical observations have been made regarding the role of caveolin-1 (Cav-1)
during cellular senescence. For example, caveolin-1 deficiency prevents reactive
oxygen species-induced cellular senescence despite mitochondrial dysfunction,
which leads to senescence. To resolve this paradox, we re-addressed the role of
caveolin-1 in cellular senescence in human diploid fibroblasts, A549, HCT116, and
Cav-1-/- mouse embryonic fibroblasts. Cav-1 deficiency (knockout or knockdown)
induced cellular senescence via a p53-p21-dependent pathway, downregulating the
expression level of the cardiolipin biosynthesis enzymes and then reducing the
content of cardiolipin, a critical lipid for mitochondrial respiration. Our
results showed that Cav-1 deficiency decreased mitochondrial respiration, reduced
the activity of oxidative phosphorylation complex I (CI), inactivated SIRT1, and
decreased the NAD+ /NADH ratio. From these results, we concluded that Cav-1
deficiency induces premature senescence via mitochondrial dysfunction and silent
information regulator 2 homologue 1 (SIRT1) inactivation.
PMID- 28514058
TI - In Situ Observation of Crystallization of Methylammonium Lead Iodide Perovskite
from Microdroplets.
AB - It is of great importance to investigate the crystallization of organometallic
perovskite from solution for enhancing performance of perovskite solar cells.
Here, this study develops a facile method for in situ observation of
crystallization and growth of the methylammonium lead iodide (MAPbI3 ) perovskite
from microdroplets ejected by an alternating viscous and inertial force jetting
method. It is found that there are two crystallization modes when MAPbI3 grows
from the CH3 NH3 I (MAI)/PbI2 /N,N-dimethylformamide (DMF) solution: needle
precursors and granular perovskites. Generally, needle Lewis adduct of MAPbI3
.DMF tends to nucleate and grow from the solution due to low solubility of PbI2 .
The growth of MAPbI3 .DMF depends on both the concentration of MAI and
temperature. It tends to form large perovskite domains on substrates at high
temperature. The MAPbI3 .DMF coverts to nanocrystalline perovskite due to lattice
shrinkage when DMF molecules escape from the Lewis adduct. Granular perovskite
can also directly nucleate from the solution at high concentration of MAI due to
compositional segregation.
PMID- 28514059
TI - [11 C]Fluoroform, a Breakthrough for Versatile Labeling of PET Radiotracer
Trifluoromethyl Groups in High Molar Activity.
AB - Positron-emission tomography (PET) is an immensely important imaging modality in
biomedical research and drug development but must use selective radiotracers to
achieve biochemical specificity. Such radiotracers are usually labeled with
carbon-11 (t1/2 =20 min) or fluorine-18 (t1/2 =110 min), but these are only
available from cyclotrons in a few simple chemical forms. [18 F]Fluoroform has
emerged for labeling tracers in trifluoromethyl groups but is severely limited in
utility by low radioactivity per mass (low molar activity). Here, the synthesis
of [11 C]fluoroform is described, based on CoF3 -mediated fluorination of
cyclotron-produced [11 C]methane. This process is efficient and repetitively
reliable. [11 C]Fluoroform shows versatility for labeling small molecules in very
high molar activity (>200 GBq MUmol-1 ), far exceeding that possible by using [18
F]fluoroform. Therefore, [11 C]fluoroform represents a major breakthrough for
labeling prospective PET tracers in trifluoromethyl groups at high molar
activity.
PMID- 28514060
TI - Improved in-tube electro-membrane extraction followed by high-performance liquid
chromatography for simple and selective determination of ionic compounds:
Optimization by central composite design.
AB - In this work, an efficient sample clean-up method, named in-tube electro-membrane
extraction, is modified to resolve the formation of bubbles in the extraction
process. This modified method is applied for the extraction of two model analytes
including tartrazine and sunset yellow from food samples. The method is based on
the electro-kinetic migration of ionized compounds by the application of an
electrical potential difference, and on this basis the analytes under
investigation, as anionic compounds, simply migrate from the donor phase and
concentrate in the acceptor phase. A thin polypropylene sheet placed in the tube
acts as a support for the membrane solvent, and it separates 30 MUL of the
aqueous acceptor from 1.2 mL of the aqueous donor. This setup can be used to
solve the problem of extracting highly hydrophilic analytes. Response surface
methodology is used for optimization of the experimental parameters so that under
the optimized conditions, the method provides a good linearity in the range of 50
1000 ng/mL, low limits of detection (15-25 ng/mL), good extraction
repeatabilities (relative standard deviations below 8.1%, n = 5), and high
extraction recoveries (54-76%).
PMID- 28514061
TI - Mapping intermediate degradation products of poly(lactic-co-glycolic acid) in
vitro.
AB - There is widespread interest in using absorbable polymers, such as poly(lactic-co
glycolic acid) (PLGA), as components in the design and manufacture of new
generation drug eluting stents (DES). PLGA undergoes hydrolysis to progressively
degrade through intermediate chemical entities to simple organic acids that are
ultimately absorbed by the human body. Understanding the composition and
structure of these intermediate degradation products is critical not only to
elucidate polymer degradation pathways accurately, but also to assess the safety
and performance of absorbable cardiovascular implants. However, analytical
approaches to determining the intermediate degradation products have yet to be
established and evaluated in a standard or regulatory setting. Hence, we
developed a methodology using electrospray ionization mass spectrometry to
qualitatively and quantitatively describe intermediate degradation products
generated in vitro from two PLGA formulations commonly used in DES. Furthermore,
we assessed the temporal evolution of these degradation products using time-lapse
experiments. Our data demonstrated that PLGA degradation products via
heterogeneous cleavage of ester bonds are modulated by multiple intrinsic and
environmental factors, including polymer chemical composition, degradants
solubility in water, and polymer synthesis process. We anticipate the
methodologies and outcomes presented in this work will elevate the mechanistic
understanding of comprehensive degradation profiles of absorbable polymeric
devices, and facilitate the design and regulation of cardiovascular implants by
supporting the assessments of the associated biological response to degradation
products. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl
Biomater, 106B: 1129-1137, 2018.
PMID- 28514063
TI - Where are you heading? Flexible integration of retinal and extra-retinal cues
during self-motion perception.
AB - As we move forward in the environment, we experience a radial expansion of the
retinal image, wherein the center corresponds to the instantaneous direction of
self-motion. Humans can precisely perceive their heading direction even when the
retinal motion is distorted by gaze shifts due to eye/body rotations. Previous
studies have suggested that both retinal and extra-retinal strategies can
compensate for the retinal image distortion. However, the relative contributions
of each strategy remain unclear. To address this issue, we devised a two
alternative-headings discrimination task, in which participants had either real
or simulated pursuit eye movements. The two conditions had the same retinal input
but either with or without extra-retinal eye movement signals. Thus, the
behavioral difference between conditions served as a metric of extra-retinal
contribution. We systematically and independently manipulated pursuit speed,
heading speed, and the reliability of retinal signals. We found that the levels
of extra-retinal contributions increased with increasing pursuit speed (stronger
extra-retinal signal), and with decreasing heading speed (weaker retinal signal).
In addition, extra-retinal contributions also increased as we corrupted retinal
signals with noise. Our results revealed that the relative magnitude of retinal
and extra-retinal contributions was not fixed but rather flexibly adjusted to
each specific task condition. This task-dependent, flexible integration appears
to take the form of a reliability-based weighting scheme that maximizes heading
performance.
PMID- 28514065
TI - Body size and form of black girls age 9 years living in central South Carolina
and eastern North Carolina.
AB - Somatic data were collected during 1986-1987 on 53 Black girls age 9 years living
in Calhoun County in rural central South Carolina. Measures of body size
(standing height, sitting height, upper limb length, lower limb height, arm
girth, hip width, and body weight), body from (lower limb height as a percentage
of sitting height, arm girth as a percentage of upper limb length, calf girth as
a percentage of lower limb height, hip width as a percentage of lower limb
height) and skin-fat thickness (over triceps and on abdomen) were analyzed for
central tendency and variability. Comparisons were made with earlier samples of
Black girls measured in rural regions of Richland County in central South
Carolina during 1975-1976 and in urban Greenville city and rural Pitt County in
eastern North Carolina during 1980-1981 as well as with earlier studies conducted
in various parts of the United States. The four same-age group samples yielded
similar means for standing height, sitting height, arm and calf girth, and body
weight. The Calhoun County girls exceeded their Pitt County, North Carolina,
peers in lower limb height, upper limb length, and lower limb height as a
percentage of sitting height. In each of the subgroups studied, the distribution
of measures for skin-fat thicknesses was, to some extent, skewed positively.
PMID- 28514064
TI - Brain-Inspired Photonic Neuromorphic Devices using Photodynamic Amorphous Oxide
Semiconductors and their Persistent Photoconductivity.
AB - The combination of a neuromorphic architecture and photonic computing may open up
a new era for computational systems owing to the possibility of attaining high
bandwidths and the low-computation-power requirements. Here, the demonstration of
photonic neuromorphic devices based on amorphous oxide semiconductors (AOSs) that
mimic major synaptic functions, such as short-term memory/long-term memory, spike
timing-dependent plasticity, and neural facilitation, is reported. The synaptic
functions are successfully emulated using the inherent persistent
photoconductivity (PPC) characteristic of AOSs. Systematic analysis of the
dynamics of photogenerated carriers for various AOSs is carried out to understand
the fundamental mechanisms underlying the photoinduced carrier-generation and
relaxation behaviors, and to search for a proper channel material for photonic
neuromorphic devices. It is found that the activation energy for the
neutralization of ionized oxygen vacancies has a significant influence on the
photocarrier-generation and time-variant recovery behaviors of AOSs, affecting
the PPC behavior.
PMID- 28514062
TI - Locoregional therapy with alpha-emitting trastuzumab against peritoneal
metastasis of human epidermal growth factor receptor 2-positive gastric cancer in
mice.
AB - Peritoneal metastasis of gastric cancer (PMGC) is incurable and thus has an
extremely poor prognosis. We have found, however, that locoregionally
administered trastuzumab armed with astatine-211 (211 At-trastuzumab) is
effective against human epidermal growth factor receptor 2 (HER2)-positive PMGC
in a xenograft mouse model. We first observed that 211 At-trastuzumab can
specifically bind and effectively kill NCI-N87 (N87) cells, which are HER2
positive human metastatic GC cells, both in vitro and in s.c. tumors. We
established a PMGC mouse model using N87 xenografts stably expressing luciferase
to test alpha-particle radioimmunotherapy with 211 At-trastuzumab against PMGC.
Biodistribution analysis in this PMGC mouse model revealed that the i.p.
administration of 211 At-trastuzumab (1 MBq) was a more efficient means of
delivery of 211 At into metastatic tumors than i.v. injection; the maximum tumor
uptake with i.p. administration was over 60% injected dose per gram of tissue
(%ID/g) compared to approximately 18%ID/g with i.v. injection. Surprisingly, a
single i.p. injection of 211 At-trastuzumab (1 MBq) was sufficient to completely
eradicate intraperitoneally disseminated HER2-positive GC xenografts in two of
six treated mice by inducing DNA double-strand breaks, and to drastically reduce
the tumor burden in another three mice. No bodyweight loss, leukocytopenia, or
significant biochemical changes in liver or kidney function were observed in the
treatment group. Accordingly, locoregionally administered 211 At-trastuzumab
significantly prolonged the survival time of HER2-positive PMGC mice compared
with control treatments. Our results provide a proof-of-concept demonstration
that locoregional therapy with 211 At-trastuzumab may offer a new treatment
option for HER2-positive PMGC.
PMID- 28514066
TI - Raymond Pearl memorial lecture, 1988: Evolution of mitochondrial DNA in human and
other organisms.
AB - Within the last ten years complete sequencing of mitochondrial DNA in human and
several other species, sequencing of nuclear and mitochondrial ribosomal and
transfer RNAs in many species of bacteria, fungi, plants, and animals, and
population studies of restriction enzyme polymorphism in the mtDNAs of insects,
mammals and sixteen species of primates produced a wide range of new data and
theory in molecular evolutionary genetics. These data support the endosymbiotic
origin of the eukaryotic cell, the evolution of the Genus Homo with Pan as the
closest related living genus, and the origin of modern Homo sapiens by
gradualistic, anagenetic, regional phyletic transformation from Homo erectus.
PMID- 28514067
TI - Fatness and fat distribution in Mexican-American children and youths from the
Hispanic health and nutrition examination survey.
AB - Mexican-American children are shorter but relatively heavier than non-Hispanic
white children. The excess relative weight is probably due to increased fat
rather than lean body mass and, more specifically, to increased fat deposition on
the upper trunk sites. The objective of this paper is to describe the level of
fatness and fat distribution in a large, representative sample of Mexican-
American children and adolescents from the recently completed Hispanic Health and
Nutrition Examination Survey (HHANES). As expected, Mexican-American children are
generally fatter than white children measured in previous national surveys
(National Health and Nutrition Examination Survey [NHANES] II, Health Examination
Survey [HES]). Differences are particularly evident for trunk skinfold
thicknesses and generally increase with age. Indices of fat distribution clearly
show a centralized, upper body adiposity pattern among Mexican-Americans, a cause
for concern since greater fat deposition on the trunk has been associated with
increased risk of certain chronic disease.
PMID- 28514069
TI - Introduction: Uses of molecular biology: Understanding the basis of genetic
disease, determining evolutionary pathways, and other applications.
PMID- 28514068
TI - DNA fingerprints in physical anthropology.
AB - Hypervariabal minisatellite DNA is a recently described class of nuclear
sequences with no known biological function. The minisatellites do form a subtype
of restricition fragment length polymorphisms possessing several characteristics
particularly intriguing to anthropologists interested in forensics, sociobiology,
primate conservation, genetic variability, and molecular evolution. The sequence
occupy at least five dozen loci scattered throughout the human genome. Unlike
many polymorphisms, many of the loci have numerous alleles each present at
similar frequencies. Such a genetic structure produces exceptionally high levels
of heterozygosity and thus provides a tool for the individualization of tissue
samples. Additionally, as the alleles are inherited in a Mendelian fashion, the
minisatellites provide a superb tool for the identification of paternity (or
maternity). Unlike standard blood groups, levels of variability are so high in
populations studied to data that parentage can be established by inclusion rather
than exclution. Homologous sequences are shown to exist in a variety of Old World
primates. Visualization of genetic fingerprints in nonhumans may allow for
determination of paternity where the pool of potential sires is available, while
also providing information on levels of genetic variability. These capabilities
will ultimately provide for better management of primate colonies. Used in
concert with behavioral data, a number of sociobiological will also become more
amenable to investigation.
PMID- 28514070
TI - Predicting smallpox epidemics: A statistical analysis of two Finnish populations.
AB - We analysis data on death due to smallpox in two subdivided Finish populations,
the relatively isolated Aland Islands and the mainland parish of Kitee. The data
span a 135-year time period (1750-1885). Logisitic regression and Cox
proportional hazards models are used to assess the effects of predictive
variables on (1) the probability that an individual subdivision experiences an
epidemic and (2) the length of the time period between two epidemics in each
subdivision. The predictive variables include population sizes, migration rates,
geographic distance, and presence or absence of vaccination. Vaccination was
found to be the single most important predicative variable (odds ratio = 6.3 in
Aland and 4.4 in Kitee). No other variable were significant predicators in Kitee,
while geographic distance was an additional significant predicator in Aland (odds
ratio = 1.05). As expected, vaccination and geographic distance were both
negatively associated with the probability of epidemic occurrence. The Mantel
regression approach was used to evaluate the effects of independent variables on
the probability that any two subdivisions experienced the same epidemic. Between
subdivision migration rates were the most important predictive variable here, and
population size was an important predictor in Aland but not in Kitee. The
differing results in these two populations are explained in terms of differences
in ecological setting and social organization.
PMID- 28514071
TI - Molecular micro- and macroevolution in the primate alpha-globin gene family.
AB - Because hemoglobin is among the most abundant and accessible proteins in the
human body, the molecular basis for its production is arguably the best-known
genetic system in any higher organism. The hemoglobin molecule is tetrameric and
consists all developmental stage of two copies of each of two components, alpha
like (141 amino acids) and beta-like (146 amino acids). The beta-like globins are
located in a tight cluster on chromosome 11 and the alpha-like globins on
chromosome 16. The alpha-globin cluster consists of several functional genes and
nonfunctional pseudogenes, each the product of an ancient duplication of
primordial genes. The cluster therefore affords us a window on the major features
of molecular evolution. Within human populations hypervariable regions exist
which may serve as useful genetic markers; and unequal crossing-over creates the
most prevalent genotypes of alpha-thalassemia. Recently a new member of the alpha
globin cluster was discovered in the orangutan genome and then subsequently in
other taxa, including Homo sapiens. It appears to encode a unique alpha-like
globin, and its protein product has yet to be isolated.
PMID- 28514072
TI - Sibling correlations for skeletal age assessments by the Fels method.
AB - Sibling correlations are reported for Fels skeletal ages from 2,622 mixed
longitudinal hand-wrist radiographs of 285 boys and 276 girls. Because the
observed correlations were irregular across age, they were smoothed by using
kernel regression. The brother-sister correlations were generally lower than
those for the other types of silbling pairs, but they were similar to the brother
brother correlations after 11 years. The sister-sister correlations were
considerably higher than the brother-brother and brother-sister correlations
after 12 years. The present data do not provide clear evidence of involvement of
the X chromosome in the timing of skeletal maturation, but after 12 years the
present data suggest such an involvement.
PMID- 28514073
TI - Application of molecular techniques to the study of human physiological
variation.
AB - Physiological differences between human populatios, manifest as apparent
adaptation to extreme environments, as differences in patterna of growth and
development, and as differences in prevalence of common disease, are a mofer
subject area of human biology. The approach of the geneticist interested in
understanding these difference has been largely that of the proverbial drunk
looking for has lost keys. We have characterized those genes whose products are
easily assayed from peripheral blood and sought post hoc statistical evidence for
a relationship between gene frequencies and physiological variables. With few
exceptions, this approach has failed to provide convincing evidence of the role
of genes in determining physiological differences between populations. This is
not unexpected since the genes which our knowledge of physiology would predict to
be important in determining physiological homeostasis. Recent advances in
molecular biology (particularly in the ability to isolate and clone specific
genes and to use these as probes to detect genomic variation-polymorphism
associated with these genes in human populations) and advances in our ability to
resolve and visualize genetic variation in protein products provide the tools for
a direct evaluation of the role of specific gene in determining physiological
differences between populations. I will review the "candidate genes" available
for the study of several physiological systems and present preliminary data from
my laboratory related to genetic determinants of lipid metabolism.
PMID- 28514074
TI - Association of adipose tissue distribution with relative skeletal age in boys:
The Fels longitudinal study.
AB - The association between relative skeletal age and fat patterning was analyzed by
using data from the Fels Longitudinal Study for boys at chronological ages 8 to
17 years. Fat patterning, as indicated by age-specific means for three skinfold
thickness indices adjusted for weight/stature2 , was peripheral between 8 and 12
years of chronological age but began to increase in a centripetal direction
towards a generalized distribution after 13 years. From 14 to 17 years of
chronological age, boys with advanced relative skeletal ages had more centripetal
fat patterns, as indicated by the ratio subscapular/(subscapular + triceps)
skinfolds, than did those with retarded skeletal ages. The mean annual increment
in this ratio was significantly greater from 13 to 14 years of chronological age
in boys with advanced relative skeletal ages than in those with retarded relative
skeletal ages. Fat pattern index scores at 17 years of chronological age,
however, could not be predicted from relative skeletal ages at 7, 11, or 14 years
after adjustment for baseline fat pattern index scores and weight/stature2 . It
was concluded that fat patterning, as quantified by the ratio indices used in
this study, was associated more strongly with other indicators of relative
maturity such as secondary sex characteristics in adolescent boys.
PMID- 28514075
TI - Comparison of different bioelectrical impedance analyzers in the prediction of
body composition.
AB - To investigate the influence of different bioelectrical impedance (BI) analyzers
on the prediction of body composition from bioelectrical resistive impedance (R),
146 healthy white adults (73 men; 73 women) were studied at two independent
laboratories: The University of Florida (UF) and the USDA, San Francisco. Whole
body R was measured on each subject with three different BI analyzers. AT UF
analyzers were: Valhalla Scientific model 1990-A (VH), RJL Systems model BIA-101
(RJL), and Medi-Fitness model 1000 (MF). At USDA analyzers were: VH, RJL, and
Bioelectrical Sciences model 200Z (BES). The largest difference in R (36 ohms, P
? 0.01) was noted between BES and VH at USDA. When applied to current BI
prediction equations, the observed differences among analyzers resulted in
differences in predicated % fat of up to 6.3% although most comparisons among
mean values (79%) showed differences below 3%. Crossvalidation of the selected BI
prediction equations with hydrostatistically determines body composition using
the different R values revealed total errors of prediction (E) ranging from 3.6
to 9.8% fat. The prediction equations were most accurate when used with data
collected on the same instrument that was to used to develop the equation (E =
3.6 to 5.3% fat). These findings indicate that different analyzers can be a
significant source of variation when predicting body composition from R. To
minimize this source of variation, it is recommended that BI prediction equations
be used with the same type of instrument as that with which they were developed.
PMID- 28514076
TI - Cellular and molecular mechanisms of neuronal degeneration: Amyotrophic lateral
sclerosis, parkinsonism-demantia, and Alzheimer disease.
AB - Hyperendemic Pacific foci of amyotrophic lateral sclerosis (ALS) and parkinsonism
dementia (PD) represent naturally occurring models of late-onset chronic
degenerative diseases that occur in different cultures, in different ecological
zones, and among genetically divergent populations. These diseases occur among
the Chamorros of the Mariana Islands, among the Auyu and Jakai of southern West
New Guinea, and among the Japanese from the Kill Peninsula of Honshu Island.
Accumulating evidence supports the hypothesis that a defect in mineral metabolism
may be etiologically involved. Toxic and essential elements, such as calcium
aluminum, and silicon cross the blood-brain barrier, deposit in affected neurons,
and disrupt the axonal transport system, resulting in the abnormal
copolymerization of cytoskeletal and amyloid beta-proteins in neurons. The
pathological accumulation of these and other proteins into neurofibrillary
tangles (the hallmark neuropathological lesion) causes neuronal dysfunction and
death. Recent immunocytochemical and biochemical studies indicate that the
amyloid beta-protein in Guamanian PD has an identical amino acid sequence, a
similar N-terminus heterogeneity (variation in polypeptide length), and a similar
immunoreactivity to those found in Alzheimer disease, suggesting a common
mechanism of pathogenesis. Investigations are now underway to determine whether
the abnormal accumulation of amyloid beta-protein in neurons of Guamanian
patients with ALS and PD is the result of an aberrant post-translational
modification of a larger precursor protein, an additional copy of the amyloid
gene, or an impairment of amyloid catabolism all of which may be mediated by
metal-enzyme or metal-gene interactions. The abnormal copolymerization of other
proteins such as neurofilament, microtubule-associated protein tau, and ubiquitin
in affected neurons suggests their interrelationship in the disease process.
PMID- 28514077
TI - Secular trends in physique and physical fitness in Japanese students during the
last 20 years.
AB - The secular trend of increase in physical size of children has often been
reported. Children today are bigger than before, but there is a question whether
their physical fitness has improved as well. Methodological differences make it
difficult to compare older and newer data. Data are presented from the tests and
measurements of physical fitness of collage students measured once a year from
1964 to 1987. Identical methods of measurement were used throughout. Sample sizes
are of about 500-2,300 for each year, and year to year changes are discussed.
Height, weight and chest grith measurements increased from 1964 to 1987 by 4.4
cm, 5.3 kg, and 3.7 cm, respectively, and their regression coefficients for the
years are .15, .24, and .15, respectively. The rate of increase of height is
greater in the first half of these years. Vital capacity, standing broad jump,
and 100 m dash records improved, but both right and left grip strength decreased.
Back strength, ball throwing, and push-up performance did not change
significantly. The results show that the size of young adults has increased, but
that their physical fitness does not always follow a similar course.
PMID- 28514078
TI - The silent zone of the lung in asthma under scrutiny again.
PMID- 28514079
TI - Bioinspired Total Synthesis of Homodimericin A.
AB - Homodimericin A is a remarkable fungal metabolite. This highly oxygenated racemic
unsaturated polyketide poses a significant synthetic challenge owing to its
sterically demanding central cagelike core containing eight contiguous
stereogenic centers (including three quaternary stereocenters) and several
carbonyl functionalities. On the basis of its proposed biogenetic synthesis, we
designed a total synthesis of homodimericin A that proceeds in seven steps and
features a double Michael reaction, an intramolecular Diels-Alder reaction, and
an ene reaction.
PMID- 28514080
TI - Methane emission from feather moss stands.
AB - Data from remote sensing and Eddy towers indicate that forests are not always net
sinks for atmospheric CH4 . However, studies describing specific sources within
forests and functional analysis of microorganisms on sites with CH4 turnover are
scarce. Feather moss stands were considered to be net sinks for carbon dioxide,
but received little attention to their role in CH4 cycling. Therefore, we
investigated methanogenic rates and pathways together with the methanogenic
microbial community composition in feather moss stands from temperate and boreal
forests. Potential rates of CH4 emission from intact moss stands (n = 60) under
aerobic conditions ranged between 19 and 133 pmol CH4 h-1 gdw-1 . Temperature and
water content positively influenced CH4 emission. Methanogenic potentials
determined under N2 atmosphere in darkness ranged between 22 and 157 pmol CH4 h-1
gdw-1 . Methane production was strongly inhibited by bromoethane sulfonate or
chloroform, showing that CH4 was of microbial origin. The moss samples tested
contained fluorescent microbial cells and between 104 and 105 copies per gram dry
weight moss of the mcrA gene coding for a subunit of the methyl CoM reductase.
Archaeal 16S rRNA and mcrA gene sequences in the moss stands were characteristic
for the archaeal families Methanobacteriaceae and Methanosarcinaceae. The
potential methanogenic rates were similar in incubations with and without methyl
fluoride, indicating that the CH4 was produced by the hydrogenotrophic rather
than aceticlastic pathway. Consistently, the CH4 produced was depleted in 13 C in
comparison with the moss biomass carbon and acetate accumulated to rather high
concentrations (3-62 mM). The delta13 C of acetate was similar to that of the
moss biomass, indicating acetate production by fermentation. Our study showed
that the feather moss stands contained active methanogenic microbial communities
producing CH4 by hydrogenotrophic methanogenesis and causing net emission of CH4
under ambient conditions, albeit at low rates.
PMID- 28514083
TI - Pustulobullous variant of SDRIFE (symmetrical drug-related intertriginous and
flexural exanthema).
PMID- 28514084
TI - The education of one spouse and the fatness of the other spouse.
AB - As shown in 702 wives with 9-12 years of education and 612 husbands similarly
educated, the summed skinfolds of one spouse are influenced by the educational
level of the other spouse, considerably so for the husbands. Women with 9-12
years of education married to men of lower educational attainment are higher in
the sum of four skinfolds while women of similar years of schooling married to
men of college education and beyond are leaner (P=0.001). Possible explanations
for the effect of the education of one spouse on the fatness level of the other
spouse include selective mating in the direction set by the husband's
socioeconomic milieu and fatness "drift" on the part of the wives, again in the
direction of the husband's socioeconomic status (SES). While these findings do
not lend themselves to a simple biological explanation, they do reiterate the
effects of socioeconomic variables on fatness level within populations and even
within families.
PMID- 28514082
TI - Universal label-free in-process quantification of influenza virus-like particles.
AB - Virus-like particles (VLPs) are becoming established as vaccines, in particular
for influenza pandemics, increasing the interest in the development of VLPs
manufacturing bioprocess. However, for complex VLPs, the analytical tools used
for quantification are not yet able to keep up with the bioprocess progress.
Currently, quantification for Influenza relies on traditional methods:
hemagglutination assay or Single Radial Immunodiffusion. These analytical
technologies are time-consuming, cumbersome, and not supportive of efficient
downstream process development and monitoring. Hereby we report a label-free tool
that uses Biolayer interferometry (BLI) technology applied on an Octet platform
to quantify Influenza VLPs at all stages of bioprocess. Human (alpha2,6-linked
sialic acid) and avian (alpha2,3-linked sialic acid) biotinylated receptors
associated with streptavidin biosensors were used, to quantify hemagglutinin
content in several mono- and multivalent Influenza VLPs. The applied method was
able to quantify hemagglutinin from crude samples up to final bioprocessing VLP
product. BLI technology confirmed its value as a high throughput analytical tool
with high sensitivity and improved detection limits compared to traditional
methods. This simple and fast method allowed for real-time results, which are
crucial for in-line monitoring of downstream processing, improving process
development, control and optimization.
PMID- 28514085
TI - Is poor early growth related to adult immune aging? A follow-up study.
PMID- 28514081
TI - Weight loss and improved metabolic outcomes amongst rural African American women
in the Deep South: six-month outcomes from a community-based randomized trial.
AB - BACKGROUND: Obesity is highly prevalent in African American women, especially
those in the rural southern USA, resulting in persistent health disparities.
OBJECTIVE: To test the effectiveness of an evidence-based behavioural weight loss
intervention delivered by community health advisors to African American women in
the rural south. DESIGN AND METHODS: Overweight or obese African American women
(30-70 years) from eight counties in Mississippi and Alabama participated in a 24
month randomized controlled trial of an evidence-based behavioural weight loss
programme augmented with community strategies to support healthy lifestyles
(Weight Loss Plus, N = 154) compared to the weight loss programme alone (Weight
Loss Only, N = 255). This study reports on 6-month outcomes on primary (weight
change) and secondary (waist circumference, blood pressure, lipids, fasting blood
glucose) outcomes, coinciding with the completion of the intensive weight loss
phase. RESULTS: Weight Loss Only participants lost an average of 2.2 kg (P <
0.001). Weight Loss Plus participants lost an average of 3.2 kg (P < 0.001). The
proportion of the total sample that lost at least 5% of their body weight was
27.1% with no difference between treatment groups. Similarly, we observed
statistically significant reductions in blood pressure, waist circumference and
triglycerides in each treatment group, with no statistical differences between
groups. CONCLUSION: Trained lay health staff and volunteers from the rural
southern USA were able to deliver a translation of a high-intensity behavioural
intervention targeted to African American women, resulting in clinically
meaningful weight loss and improvement in other metabolic outcomes in a
significant proportion of participants.
PMID- 28514086
TI - Selective migration as a bias in modernization studies: Premigration differences
in morphology and blood pressure among 15-30 year-old American Samoans.
AB - Premigration differences in anthorpometry and blood pressure are examined for
evidence of selective migration for biological characteristics. We conducted a 5
years follows-up of the migration status of 99 American Samoans 15-30 years old
who had been previously examined in 1981 and found that 33 had migrated. Analysis
of covariance of the baseline anthorpometry and blood pressures of the
nonmigrants (n = 58) and those who subsequently migrated (n = 29) indicates that
selective migration does occur among young American Samoan adults. Migrants of
both sexes tended to be younger and leaner and had significantly lower mean blood
pressures than nonmigrants even before migration. Selective migration of lean
individuals with lower blood pressures may contribute to the lower blood
pressures of migrants from American Samoa living in Hawaii or to the
heterogeneity in other Samoan populations. These results are one of the few
examples of biological selectivity demonstrated to date and illustrate the
dangers of assuming that the effects of selective migration are negligible in
studies of migration and health.
PMID- 28514087
TI - Amyotrophic lateral sclerosis and parkinsonism-dementia of Gaum: Clinical,
epidemiological, and genetic patterns.
AB - The strikingly high incidence of amyotrophic lateral sclerosis (ALS) and
parkinsonism-dementia (PD), two uniformly fatal neurodegenerative disorders which
often occur in the same families and occasionally in the same individual, was
recognized on Guam more than three decades ago. Since the first systematic
observations began, nearly 800 Guamanian Chamorro patients have been clinically
diagnosed as having either disease. The original incidence rates for ALS and PD
accounted for one in five deaths among Chamorros over ago 25. During the past 30
years, however, the incidence and mortality rates have dramatically declined and
today the risk to Guamanian chamorros is only several-fold higher than that for
non-Chamorro residents of the continental United States. The accumulating
epidemiological and genetic data strongly suggest that environmental factors are
primarily involved in the etiology and pathogenesis of these disorders. The high
incidence focus of ALS and PD on Guam and similar, but less well-studied, foci in
West New Guinea and the Kii Peninsula of Japan represent natural paradigms of
chronic degenerative disease that have provided new information and insights for
understanding not only ALS and PD, but other neurological disorders such as
classical ALS, Parkinson disease, Alzheimer disease, and early neuronal aging,
insights that might otherwise not have been forthcoming from studies of low
incidence sporadic disease in large cosmopolitan Western communities.
PMID- 28514088
TI - Dietary patterns of older adults in the United States, NHANES II 1976-1980.
AB - The second National Health and Nutrition Examination Survey (NHANES II) 1976-1980
provided detailed information concerning the dietary patterns of older Americans.
By using 24-hour dietary recall and food frequency questionnaires, the dietary
patterns of 2,615 adults aged 65-74 years were evaluated by types of living
arrangements (living alone, with a spouse, or with someone other than a spouse)
and income level (below poverty, at or above poverty). Analyzed indicators of
dietary quality were caloric and nutrient intake, food group intake and
frequency, and number of meals skipped. The most favorable dietary patterns of
elderly persons were associated with living with a spouse, especially for men.
Low-income men not living with a spouse were at highest risk of dietary
inadequacy. For women, income was more strongly associated with dietary patterns
than type of living arrangement. Results from NHANES II compare favorably to
those of the first National Health and Nutrition Examination Survey (NHANES I)
1971-1974.
PMID- 28514089
TI - Linear statistical model for growth in stature from birth to maturity.
AB - A model for the physical growth of individual children from birth to adulthood is
proposed which is linear in the model parameters. The advantages of linear over
nonlinear models include the relative ease and costs of fitting the model to data
of individuals and the fact that statistical methods are more readily available
for analysis of parameters from linear models than for nonlinear models. The
proposed linear model and the non-linear triple logistic model are both fit to
the measured lengths of two boys and two girl followed from birth to 18 years of
age.
PMID- 28514090
TI - Population biology and aging: The example of blood pressure.
AB - Cross-sectional studies of aging trends in traditional societies are open to
question because of widespread cohort trends, which can have different impacts on
different age groups. An illustration of this problem is taken from blood
pressures studies on the classic Framingham Heart Study, in which cross-sectional
results give a very different indication from longitudinal results of aging
trends in this modern population. Semilongitudinal studies of blood pressure in
Soloman Islands populations are reviewed to show the dramatic indicators in
modernising groups there of rapid blood pressure increases over approximately a
decade in adult cohorts of all ages. The partitioning of aging vs. cohort effects
is only possible with this technique.
PMID- 28514091
TI - Who gave whom hemoglobin S: The use of restriction site haplotype variation for
the interpretation of the evolution of the betaS -globin gene.
AB - The hypothesis that three separate mutations to the betaS -globin gene have
occurred in Africa in challenged. The distributions of the betaS and other beta
globin haplotypes and a simulation of the diffusion of the betaS gene are
presented and argued to be more in accord with the rapid diffusion of a single
mutant that by recombination and gene conversion now occurs on several different
haplotypes.
PMID- 28514092
TI - Are the known chronic diseases related to the human lifespan and its evolution?
AB - There is running debate in the gerontological research literature concerning the
relationship between causes of mortality and the human lifespan. Much of this
debate concerns whether we can, by biomedical intervention in known degenerative
diseases, square the human survivorship curve, at a point near some human
"maximum lifespan potential" (MLP) This paper examines the concepts of lifespan
and MLP and the relationship between the shape of the survivorship curve and the
pattern of age-specific mortality from chronic disease. The MLP need only be
viewed as a statistical phenomenon whose genetic determination relates to general
human metabolism rather than to programmed events occurring at the end of the
human lifespan. The available evidence suggests that slowing of underlying
senescence processes will not have the desired effects on survivorship, but
rather the opposite.
PMID- 28514093
TI - Development of protocols for the application of salivary steroid analysis to
field conditions.
AB - The simple and noninvasive nature of sample collection for salivary steroid assay
makes this technique well suited for anthropological field studies of human
reproduction function. In this study, a series of controlled experiments was done
to investigate the effects of modifying common clinical sample collection and
storage procedures for field use. Matched sets of samples were assayed for four
steroids to test the effects of using plastic, rather than glass, collection
tubes, of using a stimulant to aid collection, and of storing samples at ambient
temperature rather than frozen. Our work confirms the feasibility of collecting
samples for salivary steroid assay in field situations, while at the same time
emphasizing the importance of considering methodological issues in planning and
interpreting such studies. Our results show that it is acceptable to use
polystyrene collection tubes and a carefully chosen stimulant to aid collection,
and that samples can be stored at ambient temperature in the field when frozen
storage is not available. In addition, they demonstrate the necessity for
consistency in sample collection and storage procedures.
PMID- 28514094
TI - Cause-specific mortality, life expectancy, and debilitation in aging polynesians.
AB - Between 1950 and 1980 life expectancy among middle-aged American Samoan men
increased 22%; among women it increased 36%. The largest proportional increase
were observed after age 65% Men 29%, women 118%. This study examined whether
increasing longevity health of older Samoans. Cause-specific mortality data were
used to calculate multiple decrement life tables for American Samoa by decades
for both sexes from 1950 to 1979. Changes in two life table parameters were
examined: The probability of dying from, and the remaining life expectancy among
persons who would eventually die from, pneumonia/influenza, infections, cancer,
or cardiovascular disease (CVD) after birth and after age 45. Pneumonia and
infections may indicate frailty or delibitration in older individuals. The
probability of dying from a specific cause after a particular age reflects its
relative importance for survivors to that age. Residual life expectancy indicates
whether older individuals are succumbing at earlier ages or surviving longer the
risks of death from specific causes. Trends in the probability of dying from, and
life expectancy among those ultimately dying from, pneumonia and infections did
not suggest improved survival of debilitated individuals. Rather, they indicated
that older Samoans may have had greater average resistance to pneumonia and
infections in later cohorts. How much this was related to improved medical care
and availability was not clear from the available data. However, Samoans who died
from CVD and cancer did not survive longer than their counterparts had in earlier
decades. Thus, there was little opportunity for an increase in debilitation among
aging Samoans due to the longer-term survival of the chronically ill.
PMID- 28514095
TI - Relation of community size to endogamy in a traditional soceity: Patzcuaro,
Mexico, 1903-1932.
AB - Community endogamy is often a preferred cultural practice, although in
traditional populations small community size make universal endogamy difficult
for lack of appropriate mates. Using civil marriage records from an early 20th
century Tarascan Mexican population, the association of local community size,
transferred to long values, and endogamy is tested using 2,663 marriages for 40
locations situated in two municipios (counties) forming the Southwest rim of lake
Patzcuaro. The association is linear, with a correlation coefficient of 0.62 for
completely endogamous marriages and 0.55 for individual endogamy. If the two
municipio cabeceras (county seats) are removed, the r values improve to 0.83 and
0.80 (all at P < 0.001), respectively. Community size is thus important, but in a
complex settlement area central place locations, such as the cabeceras, also
exert a strong disruptive influence on the simple pattern.
PMID- 28514096
TI - Evolutionary, biosocial, and cross-cultural perspectives on the variability in
human biological aging.
AB - Because of our traditional emphasis on evolutionary processes and the causes of
variability, human biologists have contributed to the understanding of
variability in human biological aging. The shared interests of human
characterized by increased phenotypic variation in later stages of life and by
reduced adaptive capacity. The papers in this issue illustrate the unique blend
of evolutionary, biosocial, and cross-cultural perspectives used by human
biologists to study the variation in biological aging. The papers present
examples of common methodological paradigms such as theoretical/mathematical
models, epidemiological studies, natural experiments, and studies of isolated
foci of diseases. The principles of human adaptability and the premises of the
life-course perspective may provide the foundation for a conceptual framework
that integrates the study of biological, behavioral, and social aspects of human
aging. Human biologists can play an important role in refining the theoretical
and methodological tools that will be needed to understand the variability in
human aging in populations throughout the world.
PMID- 28514098
TI - Food restriction research: Its significance for human aging.
AB - The total lack of knowledge concerning the nature of the primary aging processes
coupled to the lack of biomarkers of aging has made it difficult to devise
fruitful approaches for the study of aging. Indeed, the only index of aging about
which there is general agreement is the life span of the species (i.e., the
maximum age attained by members of the species). Only one manipulation has been
found which extends the life span of a mammalian species and that is food
restriction in rodents. In addition to increasing life span, food restriction
also retards almost all age-associated physiological changes and diseases
processes. It is concluded that food restriction has these diverse actions
because it retards the primary aging processes. Recent research has been focused
on the mechanisms by which food restriction influences the primary aging
processes because it is believed that such knowledge will provide insight on the
basis nature of aging. Available evidence pints to the neural an endocrine system
as couplers of food restriction to the aging processes. Of particular current
interest are the effects of food restriction on protein turnover and free radical
metabolism. The importance of food restriction to human aging relates to the
information it is expected to yield on the nature of the primary aging processes
in all mammalian species and the database it should provide for interventions of
human aging.
PMID- 28514097
TI - Relationship between body composition and the components of somatotype.
AB - In a sample of 422 adults (200 females and 222 males) aged 18-73 years, the
relationship was determined between somatotype estimated by the Health-Carter
(Am. J. Phys. Anthropol. 27:57-74, 1967) method and body composition variables
determined by using hydrodensitometry (HD) and Bioelectrical Impedance Analysis
(BIA). The anthropometric (ANC) dimensions used to estimate somatotype were
positively correlated with the endomorphic and mesmorphic components and
negatively correlated with the ectomorphic component. For the BIA measurements,
resistance (R) was negatively correlated with the mesomorphic component; and
reactance (XC) was negatively correlated with the endomorphic component; both
measurements were positively correlated with the ectomorphic component. The HD
negative correlations were observed between mass in water and the endomorphic and
mesomorphic components, and positive correlations were observed with the
ectomorphic component. Body volume and surface area were positively correlated
with the endomorphic and mesomorphic components and negatively correlated with
the ectomorphic component. Percent fat and fat weight were related to each of the
three components of somatotype for males and females. Fat-free weight for males
was also related to the mesomorphic and the ectomorphic components.
PMID- 28514099
TI - Monthy growth increments from a longitudinal study of Canadian infants.
AB - Reference data for 1 month increments in weight, recumbent length, and head
circumference, at ages 1 to 12 months, have been derived from serial data for 351
full-term Canadian infants. This derivation was achieved by (1) fitting a family
of three parameter mathematical models to the data for each infant, (2) using
these models to estimate values 1 month apart (3) calculating 1 month increments
from the status values of 1 month intervals, (4) obtaining the distributions of
these increments, and (5) presenting the percentiles of these increments in
tables and in figures. The 1 month increments decreased with age during infancy
in each sex, and these increments tended to be more rapid for boys than for
girls. It is suggested that these reference data are suitable for the assessment
of growth rates in infants born at term in Canada or in the United States. They
can be used to assist the early identification of deviations from expected growth
rates for individuals and to compare population samples.
PMID- 28514101
TI - Rearrangement of a P4 Butterfly Complex-The Formation of a Homoleptic Phosphorus
Iron Sandwich Complex.
AB - The versatile coordination behavior of the P4 butterfly complex [{Cp'''Fe(CO)2 }2
(MU,eta1:1 -P4 )] (1, Cp'''=eta5 -C5 H2t Bu3 ) towards different iron(II)
compounds is presented. The reaction of 1 with [FeBr2 ?dme] (dme=dimethoxyethane)
leads to the chelate complex [{Cp'''Fe(CO)2 }2 (MU3 ,eta1:1:2 -P4 ){FeBr2 }] (2),
whereas, in the reaction with [Fe(CH3 CN)6 ][PF6 ]2 , an unprecedented
rearrangement of the P4 butterfly structural motif leads to the cyclo-P4 moiety
in {(Cp'''Fe(CO)2 )2 (MU3 ,eta1:1:4 -P4 )}2 Fe][PF6 ]2 (3). Complex 3 represents
the first fully characterized "carbon-free" sandwich complex containing cyclo-P4
R2 ligands in a homoleptic-like iron-phosphorus-containing molecule.
Alternatively, 2 can be transformed into 3 by halogen abstraction and subsequent
coordination of 1. The additional isolated side products, [{Cp'''Fe(CO)2 }2 (MU3
,eta1:1:2 -P4 ){Cp'''Fe(CO)}][PF6 ] (4) and [{Cp'''Fe(CO)2 }2 (MU3 ,eta1:1:4 -P4
){Cp'''Fe}][PF6 ] (5), give insight into the stepwise activation of the P4
butterfly moiety in 1.
PMID- 28514100
TI - MicroRNA-128 promotes apoptosis in lung cancer by directly targeting NIMA-related
kinase 2.
AB - BACKGROUND: MicroRNA-128 (miR-128) serves as a regulator by inducing cancer cell
apoptosis, differentiation, the epithelial-to-mesenchymal transition process, and
tumor growth by mediating different targets. NIMA-related kinase 2 (NEK2) is
aberrantly expressed in lung cancer. The miR-128/NEK2 pathway has been reported
to predict prognosis in colorectal cancer; however, the determination of a
relationship between miR-128 and NEK2 in lung cancer has remained elusive. We
explored the association between miR-128 and NEK2 in lung cancer. METHODS: MiR
128 and NEK2 expression were examined in 15 lung cancer tissues by real time-PCR.
Lung cancer SK-MES-1 cells were transfected with miR-128 mimic, an inhibitor or a
negative control. MiR-128 and NEK2 expression levels were detected using
quantitative real time-PCR and Western blot. SK-MES-1 cell apoptosis was
performed by flow cytometry. RESULTS: Compared to adjacent non-tumor tissues, miR
128 was downregulated and NEK2 was upregulated in 15 lung cancer tissues. Lung
cancer SK-MES-1 cells transfected with miR-128 mimic induced a higher apoptotic
rate than those transfected with the negative control. Dual luciferase assay
further confirmed that NEK2 was a direct target of miR-128 in lung cancer, and
transfection with miR-128 mimic could decrease the NEK2 protein level while the
miR-128 inhibitor increased NEK2 expression. Finally, the apoptotic effect of
lung cancer cells induced by miR-128 mimic could be reversed by NEK2
overexpression. CONCLUSIONS: NEK2 was regulated by miR-128 in lung cancer and miR
128 induced lung cancer cell apoptosis by mediating NEK2 expression.
PMID- 28514102
TI - Cutaneous squamous cell carcinoma treated with preoperative intraarterial
chemoradiation therapy.
PMID- 28514103
TI - Relative utility of carpal skeletal ages.
AB - The need to assess the carpal bones when a skeletal age is being obtained for a
handwrist radiograph has been determined. The mixed longitudinal data that were
analyzed had been obtained from 335 boys and 322 girls at 1, 4, 7, 10, 13, and 16
years of age. The FELS assessment method, which was used to obtain the skeletal
ages, provides the standard error of each assessment; each of these standard
errors is determined by the amount of relevant information available from a
radiograph. Utilizing the standard errors for paired assessments made with and
without the inclusion of the carpal bones, it was concluded that the carpal bones
should be assessed from 7 to 13 years in boys and from 4 to 10 years in girls,
but they need not be assessed before or after these age ranges.
PMID- 28514104
TI - Measurement of short-term growth with a new knee height measuring device.
AB - Information on short-term growth (growth over periods of 1 month or less) has
potential use in the clinic for treatment of children with growth disorders, and
knowledge about patterns of short-term growth may also contribute to an
understanding of growth control mechanisms. Limitations of measurement
reliability for most measurements of linear growth have generally confined us to
evaluation of growth over periods 3 month or longer. This report introduces the
Knee Height Measuring Device (KHMD) The Knee Height Measuring Device is available
from Intersciences Development Associates, 3508 Market St., Philadelphia, PA
19104 (215-662-0700), patent pending. , which can measure changes in size of the
lower leg of approximately 0.5 mm and thus assist in evaluation of short-term
growth. It is smaller, more portable, and less expensive than the Valk lower leg
measuring device (knemometer) and uses a less subjectively biased measurement
technique. Preliminary comparisons using a sample of 15 children measured twice
at a 28-day interval of the validity and reliability of a prototype KHMD and the
Valk knemometer. Yielded an intraobserver error of 0.295 for the KHMD and 0.206
for the knemometer. Agreement of the two instruments on the presence of
detectable growth was 90%. Pearson correlation of growth rates detected by the
two instruments was 0.73. After additional alterations improving the design and
measurement methodology of the KHMD, 103 children 6-10 years old were measured at
28-day intervals from January to June and then at 3-month intervals from June to
December of 1988 using the improved KHMD alone. Intraobserver error for these
measurements was 0.22 mm. This error was modestly associated with the weight of
the child (r=.31) but unrelated to sex, height, or growth in any dimension.
Interobserver error for 22 children measured by two observers was 0.33 mm. We
analyzed the knee height growth data primarily to test whether monthly growth
could be reliably detected by this instrument. Average 28-day knee height growth
was 1.76+/-0.3 mm, which is three times greater than the 0.5 mm growth detectable
with the KHMD. Over any given 1-month interval, fewer than 10% of the children
had growth less than that which could be detected with the instrument. We
conclude that the KHMD can reliably detect growth over a 1-month interval and has
potential clinical use for monitoring growth and for evaluating the
characteristics and associations of short-term growth.
PMID- 28514105
TI - Changes in anthropometric indices of body composition with age in a healthy
elderly population.
AB - Changes in body composition are known to occur with old age, but there is limited
knowledge of the normal values rates of change in anthropometric indices of body
composition or the distribution of these changes in the elderly. In the present
study, 98 elderly white men and 122 elderly white women were followed
prospectively for 6 years. These participants were divided into 5-years cohorts
on the basis of age at the start of the study in 1980. Separate linear
regressions of triceps skinfold thickness, midarm circumference, midarm muscle
area, and weight divided by stature squared on age were computed for each
participant. The mean annual changes or slopes for these indices were small for
each sex. A loss of subcutaneous adipose tissue was indicated with age, but the
effects of compression or measurement error may hamper the detection of changes
in indices of body composition in the elderly.
PMID- 28514106
TI - Semai Senoi mortality: Two-census method.
AB - The mortality pattern of a subpopulation of Semai Senoi of Malaysia is studied by
using a two-census method. The method yields abridged life tables for both sexes
as well as an estimate of the birth rate. The life tables show that Semai
mortality is reduced compared to estimates based on stable population methods for
the population prior to 1969. Increased health care availability seems to account
for this lower mortality.
PMID- 28514107
TI - Do reproductive patterns affect maternal nutritional status?: An analysis of
maternal depletion in Lesotho.
AB - Poor pregnancy outcomes in developing countries have often been blamed on
maternal depletion or on the cumulative nutritional drain of many closely spaced
pregnancies. Despite its widespread acceptance, the maternal depletion hypothesis
remains unproven. This study examines nutritional status and fertility history
for 873 women in highland Lesotho. Parity, age, pregnancy status, length of last
closed birth interval, open interval, and median birth interval were used to
predict nutritional status (BMI, triceps skinfold, arm muscle area). While there
is evidence that both short-term and long-term nutritional depletion are related
to lactation and pregnancy spacing, both BMI and triceps fat increase with
parity. For this population, then, the assumption of cumulative depletion due
simply to high fertility is not supported.
PMID- 28514108
TI - Validity of anthropometric percent fat prediction equations for use with pregnant
women.
AB - The purpose of this investigation was to determine the validity of five different
skinfold prediction equation for use in forecasting the percent body fat of
pregnant women. Twenty-one pregnant women underwent hydrostatic and skinfold
thickness determinations of percent body fat at 6-10, 16, and 28 weeks of
gestation. The correlations between hydrostatic and anthropometric determinations
of percent body fat were high during the three test periods (r= .78 to r = .89).
The slopes of the line of best fit between the criterion (hydrostatic weighing)
and predicted variable (prediction equation) decreased across pregnancy. The
anthropometric prediction equations tended to overestimate percent body fat
changes in comparison to the hydrostatically determined percent body fat changes.
Skinfold thickness measurements can be used as a prepregnancy aid in determining
recommended weight gain during pregnancy and as a measure of subcutaneous fat
status during pregnancy. However, anthropometric prediction equations should not
be used during the later stages of pregnancy to estimate percent fat or percent
fat changes.
PMID- 28514109
TI - The British, American NCHS, and Dutch weight standards compared using the LMS
method.
PMID- 28514110
TI - X-linked pattern of inheritance for serial measures of weight/stature2.
AB - The pattern of family resemblance for long-term serial measures of
weight/stature2 (W/S2 ) in approximately 500 individuals from the Fels
Longitudinal Growth Study suggests that X-linked genes may be contributing to the
variability in this trait among children, particularly during the prepubertal age
range of 2-9 years. In this data set, W/S2 was measured serially at the same ages
in all family members. Thus, a parent-child correlation at a specific age can be
determined even though the measurements were made on the child a generation later
than on the parent. The pattern of family resemblance at each annual age up to 10
years and at ages 14-18 years is consistent with the presence of an X-linked
genetic effect. Opposite-sex parent-child pairs are more similar than same-sex
pairs, and sister-sister pairs are more similar than brother-brother or brother
sister pairs at these ages. Furthermore, when the distribution of W/S2 is
examined separately in boys and girls, there is evidence of commingling in the
distribution of boys from 5 to 8 years of age but not in girls. This is
consistent with the existence of a major X-linked gene with a frequency of about
3%. This pattern of family resemblance and commingling suggestive of partial X
linkage for W/S2 has not been detected previously because cross-sectional family
studies generally compare individuals at different stages of growth.
PMID- 28514111
TI - Body weight/height relationship: Exponential solution.
AB - Regression of weight (W) on height (H) in all higher primates is of exponential
form W = a . exp(H . b) and is uniform for both nongrowing adults and growing
children. Parameter a values are always close to 2.0 and b to 0.02. The
exponential equation fits ontogenetic data better than the traditional allometric
power curve. The exponential nature of the W/H regression during growth may be
explained by mechanisms of cell proliferation: Arithmetic growth of the skeleton
at epiphyseal plates and geometric proliferation of many other tissues of the
body. Sexual dimorphism and interpopulational differences in a and b values are
interpretable: e.g., girls have lower initial weight (lower a values) than boys,
and Africans (low b values) grow "slimmer" than Eskimos. The effects of improved
environmental conditions can also be described. Children of the same ethnic group
have higher a and lower b values when growing in better condition because of
higher initial weights, but acquire elongated physiques during growth. Use of
exponential W/H relationship as growth standards and for reconstruction of body
build in fossil material is postulated.
PMID- 28514112
TI - Neonatal nutrition and longitudinal growth in baboons: Adiposity measured by
skinfold thickness.
AB - This paper reports the results of a 5 year longitudinal experiment that (1)
examined growth in adiposity of a group of 48 clinically normal olive savannah
baboons (Papio cynocephalus anubis) who were randomly assigned at birth to one of
three diet treatments that differed, during the first 16 weeks, in the amount of
nutrients they provided; (2) tested the hypothesis that different amounts of food
availability during the neonatal period (birth to 16 weeks) had a significant
effect on growth and development of adiposity in the subsequent infant, juvenile,
and adolescent periods; and (3) evaluated the extent to which underfed (LC) and
overfed (HC) subjects were capable of growth canalization. Each diet contained
different caloric densities but the same proportion of fat (34%), carbohydrate
(55%), and protein (11%). All animals were fed the same volume of formula;
however, HC subject were fed 40% more calories than MC subjects, who were fed 40%
more calories than the LC subjects. Growth and development of adiposity were
assessed by measuring neck, triceps, subscapular, and suprailiac skinfolds weekly
from birth to 16 weeks and at 13 week intervals from 26 to 260 weeks of age. We
found that during the first 16 weeks of the experiments, baboon growth was
strongly influenced by food shortages but not by excesses; however, when the
dietary treatment ceased, growth appeared to be strongly regulated by a genetic
component (developmental canalization) and tended to return to a more normal
growth pattern within a 26 week time frame. Males and females exhibited
differences in adipose development in that males did not exhibit residual
treatment effects while females tended to retain the effects of neonatal dietary
treatments through early adolescence.
PMID- 28514113
TI - Semai Senoi fertility and population dynamics: Two-census method.
AB - The fertility and parameters of population growth of the Semai Senoi of Malaysia
are studied by using a two-census method based on nonstable population theory.
Semai fertility is shown to be moderately high; female completed fertility is
7.42 children and the crude birth rate is greater than 0.050. Previous estimates
of Semai mortality rates are also moderately high but are insufficient to balance
birth; thus, the overall rate of growth is presently nearly 2%. Compared with an
earlier description of the pre-1969 Semai population, fertility has increased
markedly leading to a nearly threefold increase in the annual growth rate.
PMID- 28514114
TI - Finding Relevant Parameters for the Thin-film Photovoltaic Cells Production
Process with the Application of Data Mining Methods.
AB - A data mining approach is proposed as a useful tool for the control parameters
analysis of the 3-stage CIGSe photovoltaic cell production process, in order to
find variables that are the most relevant for cell electric parameters and
efficiency. The analysed data set consists of stage duration times, heater power
values as well as temperatures for the element sources and the substrate - there
are 14 variables per sample in total. The most relevant variables of the process
have been found based on the so-called random forest analysis with the
application of the Boruta algorithm. 118 CIGSe samples, prepared at Institut des
Materiaux Jean Rouxel, were analysed. The results are close to experimental
knowledge on the CIGSe cells production process. They bring new evidence to
production parameters of new cells and further research.
PMID- 28514115
TI - Rhodium-Catalyzed Regioselective Domino Azlactone-Alkyne Coupling/Aza-Cope
Rearrangement: Facile Access to 2-Allyl-3-oxazolin-5-ones and Trisubstituted
Pyridines.
AB - Rhodium-catalyzed regioselective addition of azlactones to internal alkynes
combined with aza-Cope rearrangement provides efficient atom economic access to 2
allyl-3-oxazolin-5-one derivatives. Extension to a triple domino process, in
which the above process is combined with in situ azlactone formation starting
from amino acids renders this process even more attractive. Subsequent
thermolysis of the 2-allyl-3-oxazolines enabled the de novo synthesis of
trisubstituted pyridines.
PMID- 28514117
TI - Tailored Ahp-cyclodepsipeptides as Potent Non-covalent Serine Protease
Inhibitors.
AB - The S1 serine protease family is one of the largest and most biologically
important protease families. Despite their biomedical significance, generic
approaches to generate potent, class-specific, bioactive non-covalent inhibitors
for these enzymes are still limited. In this work, we demonstrate that Ahp
cyclodepsipeptides represent a suitable scaffold for generating target-tailored
inhibitors of serine proteases. For efficient synthetic access, we developed a
practical mixed solid- and solution-phase synthesis that we validated through
performing the first chemical synthesis of the two natural products Tasipeptin A
and B. The suitability of the Ahp-cyclodepsipeptide scaffold for tailored
inhibitor synthesis is showcased by the generation of the most potent human HTRA
protease inhibitors to date. We anticipate that our approach may also be applied
to other serine proteases, thus opening new avenues for a systematic discovery of
serine protease inhibitors.
PMID- 28514118
TI - Anaphylactic shock caused by intradermal testing with cefuroxime.
PMID- 28514116
TI - Changes in main pulmonary artery diameter during follow-up have prognostic
implications in pulmonary arterial hypertension.
AB - BACKGROUND AND OBJECTIVE: A dilated pulmonary artery (PA) is a common finding in
patients with pulmonary arterial hypertension (PAH). Little is known on the
variations in PA size over time and whether these changes track with disease
severity and/or predict long-term survival. METHODS: We included patients with
PAH who had at least two computed tomography (CT) scans of the chest done on
different visits. Both scans matched the use of i.v. contrast. RESULTS: Pairs of
CT scans were compared in 113 PAH patients. During a median (interquartile range
(IQR)) time difference between scans of 8 (IQR: 3.5-20.0) months, we noted an
increase in main PA diameter of 0.5 +/- 1.8 mm (mean +/- SD) (P = 0.008). When CT
scans were performed >12 months apart (n = 47), the main PA diameter increased or
decreased by >1 mm in 40% and 13% of the patients, respectively. An increase in
main PA diameter was associated with lower PA compliance, higher right
ventricular (RV) systolic pressure, worse RV function and a decline in 6-min walk
distance. During a median (IQR) follow-up of 33 (IQR: 4.5-47) months, 53 (46.9%)
patients died. The change in PA diameter was a significant predictor of mortality
(hazard ratio (HR) per mm increase: 1.33 (95% CI: 1.11-1.61), P = 0.002) when
adjusted for difference in time and slice thickness between CT scans, age,
gender, PAH aetiology and pulmonary vascular resistance. CONCLUSION: In PAH
patients, an increase in CT-derived main PA diameter over time is associated with
progression in pulmonary pressures, RV dysfunction, a decline in functional
capacity and higher mortality.
PMID- 28514119
TI - Soft, slightly tender perianal nodules.
PMID- 28514121
TI - [SHIFT WORK AND ITS HEALTH HAZARDS].
AB - INTRODUCTION: Work in repeated changing shifts, in general, and night-shifts, in
particular, is considered a necessity, encompassing many professions, among them
physicians and nurses. This type of work has been shown to adversely affect the
normal function of the human body circadian rhythm. This negative influence in
turn, is considered to increase characteristic types of morbidity such as
metabolic syndrome, type 2 diabetes and increased rate of cardiovascular
morbidity. Women working in night-shifts in particular, have been found to face
increased rates of breast cancer, as well as menstrual disturbances and decreased
fertility. Despite many physiologic explanations for the deleterious effects of
changing or night-shifts on human's health, there is no clear notion for the
prevention or treatment of these health hazards. In light of the necessity for
such a mode of employment in our modern world, the issues of taking care of the
affected workers should be considered on a national scale.
PMID- 28514122
TI - [IS ANTI-THROMBOTIC PROPHYLAXIS WARRANTED IN FERTILITY AND IN-VITRO FERTILIZATION
TREATMENTS?]
AB - INTRODUCTION: Assisted reproductive technology (ART) treatments are potential
risk factors for thromboembolism (TE) due to excessive estrogen levels. Recently,
several studies have shed new light on this matter. AIMS: To review the
literature to assess the risk for TE during ART and to establish guidelines
regarding thrombophylaxis. METHODS: A search was conducted of PubMed, Medline,
Cochrane and clinicaltrials.gov. The search terms were fertility, assisted
reproductive technology, IVF, thromboembolism, thrombosis and anticoagulation.
Case reports and reviews were excluded. RESULTS: Three cohort studies and one
cross-sectional study were included; one examined the effect of ART on TE risk
after cycles not resulting in pregnancy. The others evaluated TE risk if
pregnancy was achieved. The rate of TE for 75,141 cycles not resulting in
pregnancy was not higher than controls in the general population. The three
studies which compared TE risk when pregnancies were achieved found that ART
increased the risk for TE primarily during the first trimester. If ovarian
hyperstimulation syndrome (OHSS) was present the risk increased further. The risk
for TE after frozen embryo replacement cycles was not increased. CONCLUSIONS: ART
posed a risk factor for TE during pregnancy, but not during ovarian stimulation
or in cycles not resulting in pregnancy. Thrombophylaxis is not indicated for all
women undergoing ART. Women with OHSS should be given thrombophylaxis during the
acute episode and throughout the first trimester. Caution is advised for patients
with combined risk factors and treatment should be individualized. Guidelines for
thromboprophylaxis are provided.
PMID- 28514123
TI - [Telemedicine: a novel service in pediatric emergency care].
AB - INTRODUCTION: Telemedicine is a field that deals with monitoring and caring for
patients who are physically apart from the caregivers, so they cannot communicate
without technological means. The use of telemedicine has been recognized by a
number of official organizations worldwide. This article reviews a unique
service, "pediatrician online", provided by Clalit HMO, through Medtrix Ltd, with
Schneider Children's Hospital specialists' supervision. With this service,
parents can receive medical consultation from pediatricians beyond community
clinic hours. The service is provided by telephone, computer or a mobile
application, and when possible video calls are made. AIMS: To describe and
analyze four years of telemedicine experience of the "pediatrician online"
service. METHODS: A retrospective study was performed including analysis of all
consultation calls conducted between November 2009 (the beginning of the project)
and December 2013. Every call to the service was recorded and documented.
Furthermore, analysis was conducted of follow-up calls to 4% of the applicants in
order to monitor medical outcome and satisfaction. RESULTS: During the first four
years approximately half a million consultation calls were provided. The average
time from referral to obtaining medical advice was eight minutes. The duration of
the consultation was four and a half minutes on average. Most of the calls were
related to young children under 4 years (74%), dealing with common pediatric
problems - fever (23%), respiratory complaints (17%), and gastrointestinal
problems (12%). One-third of the applicants intended to go to the emergency
department before they called the service, but only about one-sixth were referred
at the end of the consultation. Among those referred, only about 60% actually
went to the emergency department. The use of video-calls has been increasing, and
reached an average of 30% of the applications. Satisfaction with the service was
very high according to surveys, scoring 9.8 out of ten. Eighty-two percent of
patients sampled reported medical improvement on the next day. CONCLUSIONS: There
is a very high demand for consulting pediatricians beyond clinic hours. The use
of telemedicine, as provided by the "pediatrician online" service, addresses this
need safely and effectively with high patient satisfaction. Discussion: The use
of telemedicine is expected to expand. In order to ensure its proper use while
recognizing the capabilities and limitations, controlled studies should be
conducted, exploring the outcome of different approaches in various situations.
PMID- 28514120
TI - Mouth development.
AB - A mouth is present in all animals, and comprises an opening from the outside into
the oral cavity and the beginnings of the digestive tract to allow eating. This
review focuses on the earliest steps in mouth formation. In the first half, we
conclude that the mouth arose once during evolution. In all animals, the mouth
forms from ectoderm and endoderm. A direct association of oral ectoderm and
digestive endoderm is present even in triploblastic animals, and in chordates,
this region is known as the extreme anterior domain (EAD). Further support for a
single origin of the mouth is a conserved set of genes that form a 'mouth gene
program' including foxA and otx2. In the second half of this review, we discuss
steps involved in vertebrate mouth formation, using the frog Xenopus as a model.
The vertebrate mouth derives from oral ectoderm from the anterior neural ridge,
pharyngeal endoderm and cranial neural crest (NC). Vertebrates form a mouth by
breaking through the body covering in a precise sequence including specification
of EAD ectoderm and endoderm as well as NC, formation of a 'pre-mouth array,'
basement membrane dissolution, stomodeum formation, and buccopharyngeal membrane
perforation. In Xenopus, the EAD is also a craniofacial organizer that guides NC,
while reciprocally, the NC signals to the EAD to elicit its morphogenesis into a
pre-mouth array. Human mouth anomalies are prevalent and are affected by genetic
and environmental factors, with understanding guided in part by use of animal
models. WIREs Dev Biol 2017, 6:e275. doi: 10.1002/wdev.275 For further resources
related to this article, please visit the WIREs website.
PMID- 28514125
TI - [LETTERS TO THE EDITOR].
PMID- 28514124
TI - [PARTIAL BREAST RECONSTRUCTION BY MODIFIED BREAST REDUCTION TECHNIQUES].
AB - INTRODUCTION: Partial resections of the breast are more than 50% of breast
oncological surgery. The resulting defect can be substantial and cause meaningful
deformity that leads to reduced body image satisfaction of the patients,
affecting their ability to cope with the cancer. Parallel to the development of
breast oncology techniques, an evolution of breast reconstruction techniques
occurred. During the last decade, by using techniques from cosmetic breast
surgery (such as breast reductions, augmentations and mastopexies), we can
reconstruct extensive partial defects of the breasts at the immediate and delayed
setting and achieve symmetrical aesthetic results. Of the 350 oncological breast
surgeries a year performed in our center, 70% undergo partial breast resection
and only 10% of those surgeries exhibit a defect necessitating reconstruction.
The recovery and post-operative complications, especially in the immediate
setting, are significantly reduced in comparison to total breast reconstruction.
Our experience shows that by using plastic surgery techniques in those
operations, we can overcome the deformity created by large partial resection of
the breast and improve the mental recovery from breast cancer.
PMID- 28514126
TI - [HAPTOGLOBIN POLYMORPHISM AS AN INDEPENDENT PREDICTOR OF DIABETIC NEPHROPATHY AND
RETINOPATHY].
AB - INTRODUCTION: The antioxidant protein haptoglobin (Hp) plays a major role in the
development of diabetic complications such as diabetic nephropathy and
retinopathy. In humans, two alleles of Hp were identified: 1 and 2 with three
possible genotypes: 1-1, 2-1, and 2-2. The Hp protein products differ in their
biochemical and biophysical properties, such as their antioxidant capacity. The
Hp1 protein is superior to the Hp2 protein in binding to free hemoglobin and
neutralizing its oxidative potential and the accompanying renal and retinal
injury. Hence, diabetic patients with different Hp phenotypes have variable
susceptibility to developing diabetic nephropathy and retinopathy. In diabetes,
the kidney and the retinal injury progress gradually over time. Thus,
understanding the factors that mediate the aggravation and progression of these
complications is of critical importance. One of the latest hypotheses regarding
the involvement of haptoglobin in the development of diabetic complications is
its contribution to impaired vitamin D activation in the kidney. Over the last
few years, great efforts were made in the field to explore this notion and
decrypt the mechanism behind it. The goal in this area is that the research
findings will be translated into clinical practice and lead to the development of
a pharmacogenomics clinical approach that will deal with diabetic complications
by selective administration of vitamin D according to the Hp genotype.
PMID- 28514127
TI - [IS IT POSSIBLE TO REDUCE THE INCIDENCE OF CONGENITAL ANOMALIES? ANALYSIS OF
ADVERSE OBSTETRICS CLINICAL EVENTS].
PMID- 28514128
TI - [TREATMENT FOR OSTEOARTHRITIS OF THE KNEE].
AB - INTRODUCTION: Osteoarthritis is the most common joint disorder in the world and
its incidence is rising. In Western populations it is one of the most frequent
causes of pain, loss of function and disability in adults. The estimated lifetime
risk for knee osteoarthritis is approximately 40% in men and 47% in women. The
diagnosis of osteoarthritis is complex due to a lack of specific physical and/or
laboratorial findings. The American College of Rheumatology (ACR) has recommended
using the following criteria for the diagnosis of knee osteoarthritis: chronic
knee pain (lasting for more than 6 weeks) and at least three of the following: *
Age over 50 years old. * Morning knee stiffness lasting up to 30 minutes. *
Crepitus with active motion * Tenderness on bony palpation * Thickening or growth
of the bones * No local heat on palpation Treatment of osteoarthritis involves
alleviating pain, attempting to rectify mechanical misalignment, and identifying
and addressing manifestations of joint instability. The American Academy of
Orthopedic Surgeons (AAOS) has conducted a systematic review of the current
scientific and clinical research and has issued clinical practice guidelines
containing fifteen recommendations for the treatment of osteoarthritis of the
knee, and include only less invasive alternatives to total or partial knee
arthroplasty. This review presents the background, diagnosis, treatment and a
summary of the AAOS guidelines regarding "Treatment of Osteoarthritis of the
Knee".
PMID- 28514129
TI - [HAND INJURIES IN ROCK CLIMBERS].
AB - INTRODUCTION: Rock climbing, whether practiced in nature on cliffs and boulders
or indoors on walls made of resin and wood, has gained tremendous popularity in
recent decades. More people are exposed to injuries associated with the unique
biomechanical forces of rock climbing. A series of repetitive high torque
movements of the upper limbs are needed to ascend a wall or rockface. These
movements subject the hand and wrist to large forces, potentially resulting in
ligament and tendon sprains or rupture and even bone fracture. This review
describes the anatomy, biomechanics and the common hand injuries in rock
climbers.
PMID- 28514130
TI - [MEASURING ADHERENCE TO SELF-CARE GUIDELINES FOR PATIENTS WITH TYPE 2 DIABETES
WITH DIABETIC ULCERS ADMITTED to THE ORTHOPEDIC REHABILITATION DEPARTMENT AT TEL
HASHOMER HOSPITAL DURING 2012-2013].
AB - INTRODUCTION: Diabetic foot is a devastating complication of diabetes and
represents the major cause of lower limb amputations in the western world in the
21st century. The World Health Organization predicts a dramatic increase in the
number of diabetes patients over the next decade and by the year 2025, their
number is expected to increase to 300 million. AIMS: Examine whether training
leads to improving performance in the built-in self-care guidelines in patients
with type 2 diabetes who were hospitalized with diabetic ulcers in the Orthopedic
Rehabilitation Ward in Tel Hashomer between the years 2012-2013. METHODS: The
study included 68 type 2 diabetic patients with diabetic ulcer aged 30-80 years,
regardless of gender, who were hospitalized following a worsening ulcer. The
research tools included demographic, medical and self-care diligence
questionnaires and HbA1c measurements in a sugar balance report. RESULTS: Results
show significant change in eating habits, number of patient measurements
performed during the week and treatment of the diabetic foot between the
treatment group and the control group. In addition, support has been found to
positively affect self-care response. The only variable where no benefit changes
could be observed was the medicines consumption variable. DISCUSSION:
Prescriptive guidance, routinely performed, results in improvement in self-care
among diabetic patients. Mentoring is enabling people to understand the
importance of carrying out instructions received.
PMID- 28514131
TI - [TREATMENT OF ACHILLES TENDON RUPTURES].
AB - INTRODUCTION: Achilles tendon ruptures cause considerable morbidity and
functionality reduction. There is lack of consensus regarding the best option for
treatment following acute Achilles tendon rupture. Recent studies have failed to
show substantial difference in outcome following conservative or operative
treatment using an early active rehabilitation program. Meta-analyses have shown
that conservative management has increased the risk of re-rupture, whereas
operative intervention carries risks of complications related to the wound and
iatrogenic nerve injury. This article reviews the updated literature-based
guidelines for the treatment of Achilles tendon tears.
PMID- 28514132
TI - [ASSESSING THE SHORT AND LONG TERM EFFECT OF VIDEO-ASSISTED THORACIC SURGERY
LOBECTOMY IN OCTOGENARIAN PATIENTS].
AB - BACKGROUND: Lung cancer is a leading deadly malignancy, both in men and women,
with an increasing cancer diagnosis risk with age. Although thoracic surgery
techniques have evolved and now include Video Assisted Thoracic Surgery (VATS),
older operable lung cancer patients are still operated on less compared to the
younger population. This study aimed at investigating the postoperative
morbidity, mortality, and long-term quality of life in our pool of octogenarian
patients. METHODS: Octogenarians with newly diagnosed lung cancer at a clinical
operable stage undergoing VATS procedures were reviewed. All patients had a
clinical evaluation of their malignant stage. Patients' long-term quality of life
(QOL) and performance status were evaluated using an institutional telephone
questionnaire and the Karnofsky score at least 12 months postoperatively.
RESULTS: Between January 2009 to April 2012, 22 patients underwent VATS lobectomy
(median age: 82 years). In four cases (18%) the procedure was converted to open
thoracotomy. Patient follow-up periods ranged from 22 to 52 months. All but one
patient were released to their homes. Lung malignancy was diagnosed in 19
patients. Pathological staging ranged from IA to IIB. Three patients had a non
malignant lung lesion on final pathology. Median postoperative hospital stay was
6 days. During the first 18 months post-surgery, no mortalities were recorded in
this case study. The Karnofsky performance score yielded a median of 90. A
telephone questionnaire revealed that all patients were free of operation-related
physical limitations. All but one patient described the surgical experience as
nontraumatic. CONCLUSIONS: Current findings support the belief that today
surgeons should not deny octogenarian patients the possibility of oncological
lung surgery based solely on the patients' chronological age.
PMID- 28514133
TI - [THE INFLUENCE OF THE ISRAELI LEGISLATION ON THE RELATIONSHIP BETWEEN PHYSICIANS
AND PHARMACEUTICAL COMPANIES].
AB - INTRODUCTION: The relationship between physicians and pharmaceutical-companies
raises many dilemmas. There are two types of solutions to these dilemmas: self
regulation and government regulation. Our goal was to review in what way
legislative intervention and self-regulation standardize and affect the
relationship. In addition, we examined the positions of relevant stakeholders
regarding: 1. The relationship between physicians and pharmaceutical companies;
2. Future measures we should take to address the ethical dilemmas inherent in
this relationship. METHODS: 1. In-depth interviews with 42 senior representatives
of all the relevant stakeholders, with emphasis on their organizational identity,
since their points of view are influenced and shaped by organizational and
professional positioning. We analyzed the interviews using the Narralizer
program. 2. Analysis of three databases: The Ministry of Health, The Israel
Medical Association and Pharma-Israel, regarding donations made to various
parties in the health system. RESULTS: The influence of Israeli legislation on
the relationship between physicians and pharmaceutical companies is almost
imperceptible. However, in recent years, there have been changes in this
relationship stemming from international self-regulation, which leads to:
contractual relationships, decreases in hospitality and tighter internal control
over this relationship. CONCLUSIONS: Regulation in Israel is not achieving its
goal satisfactorily. Solutions to reduce the influence of this relationship
exist. However, the first step is for the regulator to decide to what extent, if
any, he wants to deal with this issue. If the regulator chooses to take the lead
on this issue, we will soon face additional legislation that might limit the
amount of money that the pharmaceutical companies can donate to healthcare
organizations.
PMID- 28514134
TI - [WELL-CHILD VISITS REGARDING GROWTH AND DEVELOPMENT OF INFANTS: A CROSS-CULTURAL
COMPARISON].
AB - AIMS: 1. To examine the rate of WCV among mothers in four ethno-cultural groups:
native-born Jewish, Bedouin and immigrants from the Former Soviet Union (FSU) and
Ethiopia; 2. to test the relationship between WCV in the first and second year of
the infant's life; 3. to assess the effect of sociodemographic variables on WCV.
BACKGROUND: Consistent infant well-child visits (WCV) have been found to be
related to better health status and a decrease in visits to the emergency room
and hospitalizations. METHODS: The data were collected in the Beer Sheva district
among community-dwelling women in the years 2010-2012. The quota sample comprised
of 400 mothers: 100 from each group. The inclusion criteria were: age (18-35
years old), either first or second child, or age of the youngest child between 18
24 months. Immigrant mothers lived in Israel for at least 10 years. The
monitoring of WCV was evaluated according to the registered number of visits in
the well-baby clinic registration card. RESULTS: Mothers from all groups
completed fewer WCV than the recommended number. The highest rate of visits was
observed among the immigrants from the FSU, and the lowest rate among the Bedouin
mothers (p<.001). Mothers of higher economic status had a higher rate of WCV (b =
0.38, p < 0.001). The rate of WCV in the second year was a function of the rate
of WCV in the first year (b = 0.51, p < 0.001). CONCLUSIONS: Medical personnel
treating infants should address the ethno-cultural and economic background of
mothers. It is important to give mothers information about preventive medicine at
an early stage in the infant's life and to encourage mothers in general and
Bedouin mothers in particular to comply with recommendations regarding WCV.
PMID- 28514135
TI - Three-Dimensional Hetero-Integration of Faceted GaN on Si Pillars for Efficient
Light Energy Conversion Devices.
AB - An important pathway for cost-effective light energy conversion devices, such as
solar cells and light emitting diodes, is to integrate III-V (e.g., GaN)
materials on Si substrates. Such integration first necessitates growth of high
crystalline III-V materials on Si, which has been the focus of many studies.
However, the integration also requires that the final III-V/Si structure has a
high light energy conversion efficiency. To accomplish these twin goals, we use
single-crystalline microsized Si pillars as a seed layer to first grow faceted Si
structures, which are then used for the heteroepitaxial growth of faceted GaN
films. These faceted GaN films on Si have high crystallinity, and their threading
dislocation density is similar to that of GaN grown on sapphire. In addition, the
final faceted GaN/Si structure has great light absorption and extraction
characteristics, leading to improved performance for GaN-on-Si light energy
conversion devices.
PMID- 28514136
TI - Highly Selective Volatile Organic Compounds Breath Analysis Using a Broadly
Tunable Vertical-External-Cavity Surface-Emitting Laser.
AB - A broadly tunable mid-infrared vertical-external-cavity surface-emitting laser
(VECSEL) is employed in a direct absorption laser spectroscopic setup to measure
breath acetone. The large wavelength coverage of more than 30 cm-1 at 3.38 MUm
allows, in addition to acetone, the simultaneous measurement of isoprene,
ethanol, methanol, methane, and water. Despite the severe spectral interferences
from water and alcohols, an unambiguous determination of acetone is demonstrated
with a precision of 13 ppbv that is achieved after 5 min averaging at typical
breath mean acetone levels in synthetic gas samples mimicking human breath.
PMID- 28514137
TI - Manifestation of Geometric and Electronic Shell Structures of Metal Clusters in
Intercluster Reactions.
AB - Monolayer protected clusters exhibit rich diversity in geometric and electronic
structures. However, structure-reactivity relationships in these clusters are
rarely explored. In this context, [Ag44(SR)30]4-, where -SR is an alkyl/aryl
thiolate, is an interesting system due to its geometrically and electronically
closed-shell structures and distinct charge states. We demonstrate that these
structural features of [Ag44(SR)30]4- are distinctly manifested in its solution
state reaction with another cluster, [Au25(SR)18]-. Through this reaction, an
alloy cluster anion, [Au12Ag32(SR)30]4-, evolves spontaneously as revealed by
high-resolution electrospray ionization mass spectrometry. Ultraviolet-visible
absorption spectroscopy and density functional theory calculations indicate that
[Au12Ag32(SR)30]4- is formed by the substitution of all of the Ag atoms in the
innermost icosahedral shell of [Ag44(SR)30]4- and the abundance is attributed to
its higher stability due to closed geometric as well as electronic shell
structure, similar to the reactant clusters. We further demonstrate that the
substitution of metal atoms in the middle dodecahedral shell and the outermost
mount sites are also possible, however such substitutions produce AuxAg44-x(SR)30
alloy clusters with geometrically and electronically open shells. Depending on
specific sites of substitution, an unexpected superatom-nonsuperatom transition
occurs in the distribution of AuxAg44-x(SR)30 alloy clusters formed in this
reaction. Our results present a unique example of a structure-reactivity
relationship in the metal atom substitution chemistry of monolayer protected
clusters, wherein a systematic trend, reflecting the geometric and the electronic
shell structures of the reactant as well as the product clusters, was observed.
PMID- 28514138
TI - Manipulating Ion Migration for Highly Stable Light-Emitting Diodes with Single
Crystalline Organometal Halide Perovskite Microplatelets.
AB - Ion migration has been commonly observed as a detrimental phenomenon in
organometal halide perovskite semiconductors, causing the measurement hysteresis
in solar cells and ultrashort operation lifetimes in light-emitting diodes. In
this work, ion migration is utilized for the formation of a p-i-n junction at
ambient temperature in single-crystalline organometal halide perovskites. The
junction is subsequently stabilized by quenching the ionic movement at a low
temperature. Such a strategy of manipulating the ion migration has led to
efficient single-crystalline light-emitting diodes that emit 2.3 eV photons
starting at 1.8 V and sustain a continuous operation for 54 h at ~5000 cd m-2
without degradation of brightness. In addition, a whispering-gallery-mode cavity
and exciton-exciton interaction in the perovskite microplatelets have both been
observed that can be potentially useful for achieving electrically driven laser
diodes based on single-crystalline organometal halide perovskite semiconductors.
PMID- 28514139
TI - Bioorthogonal Protein Conjugation: Application to the Development of a Highly
Sensitive Bioluminescent Immunoassay for the Detection of Interferon-gamma.
AB - Bioorthogonal conjugation eliminates the shortcomings of classical conjugation
methods. The conjugation of antibodies to reporter proteins, such as
bioluminescent protein, can be controlled with orthogonal conjugation methods.
Here we report a bioluminescent immunoassay for the sensitive detection of
interferon-gamma (IFN-gamma) that utilizes orthogonal conjugation of
bioluminescent protein, Gaussia luciferase to anti-IFN-gamma antibody. The IFN
gamma is produced by the immune system and the detection of the IFN-gamma is
pivotal for the detection of persistent viral and bacterial infections. A
bioorthogonal conjugation approach is used to conjugate an anti-IFN-gamma
antibody with a GLuc mutant containing the N-terminal tyrosine using
formylbenzene diazonium hexafluorophosphate reagent (FBDP) in hydrophilic mild pH
environment yielding high conjugation efficiency (60%). This reagent is shown to
be specific for tyrosine (Tyr) residues. Therefore, conjugation through Tyr was
orthogonal and not detrimental to the bioluminescence activity of GLuc. The
immunoassay described in this paper is a sandwich type assay and involves a
capture and a detection antibody. The assay was validated for its robustness,
precision, accuracy, limit of detection, and recovery.
PMID- 28514140
TI - Properties of Intermediates in the Catalytic Cycle of Oxalate Oxidoreductase and
Its Suicide Inactivation by Pyruvate.
AB - Oxalate:ferredoxin oxidoreductase (OOR) is an unusual member of the thiamine
pyrophosphate (TPP)-dependent 2-oxoacid:ferredoxin oxidoreductase (OFOR) family
in that it catalyzes the coenzyme A (CoA)-independent conversion of oxalate into
2 equivalents of carbon dioxide. This reaction is surprising because binding of
CoA to the acyl-TPP intermediate of other OFORs results in formation of a CoA
ester, and in the case of pyruvate:ferredoxin oxidoreductase (PFOR), CoA binding
generates the central metabolic intermediate acetyl-CoA and promotes a 105-fold
acceleration of the rate of electron transfer. Here we describe kinetic,
spectroscopic, and computational results to show that CoA has no effect on
catalysis by OOR and describe the chemical rationale for why this cofactor is
unnecessary in this enzymatic transformation. Our results demonstrate that, like
PFOR, OOR binds pyruvate and catalyzes decarboxylation to form the same
hydroxyethylidine-TPP (HE-TPP) intermediate and one-electron transfer to generate
the HE-TPP radical. However, in OOR, this intermediate remains stranded at the
active site as a covalent inhibitor. These and other results indicate that, like
other OFOR family members, OOR generates an oxalate-derived adduct with TPP
(oxalyl-TPP) that undergoes decarboxylation and one-electron transfer to form a
radical intermediate remaining bound to TPP (dihydroxymethylidene-TPP). However,
unlike in PFOR, where CoA binding drives formation of the product, in OOR, proton
transfer and a conformational change in the "switch loop" alter the redox
potential of the radical intermediate sufficiently to promote the transfer of an
electron into the iron-sulfur cluster network, leading directly to a second
decarboxylation and completing the catalytic cycle.
PMID- 28514142
TI - Nonmonotonic Self-Deformation of Cell Nuclei on Topological Surfaces with
Micropillar Array.
AB - Cells respond to the mechanical signals from their surroundings and integrate
physiochemical signals to initiate intricate mechanochemical processes. While
many studies indicate that topological features of biomaterials impact cellular
behaviors profoundly, little research has focused on the nuclear response to a
mechanical force generated by a topological surface. Here, we fabricated a
polymeric micropillar array with an appropriate dimension to induce a severe self
deformation of cell nuclei and investigated how the nuclear shape changed over
time. Intriguingly, the nuclei of mesenchymal stem cells (MSCs) on the
poly(lactide-co-glycolide) (PLGA) micropillars exhibited a significant initial
deformation followed by a partial recovery, which led to an "overshoot"
phenomenon. The treatment of cytochalasin D suppressed the recovery of nuclei,
which indicated the involvement of actin cytoskeleton in regulating the recovery
at the second stage of nuclear deformation. Additionally, we found that MSCs
exhibited different overshoot extents from their differentiated lineage,
osteoblasts. These findings enrich the understanding of the role of the cell
nucleus in mechanotransduction. As the first quantitative report on nonmonotonic
kinetic process of self-deformation of a cell organelle on biomaterials with
unique topological surfaces, this study sheds new insight into cell-biomaterial
interactions.
PMID- 28514141
TI - Subtype-Specific Agonists for NMDA Receptor Glycine Binding Sites.
AB - A series of analogues based on serine as lead structure were designed, and their
agonist activities were evaluated at recombinant NMDA receptor subtypes (GluN1/2A
D) using two-electrode voltage-clamp (TEVC) electrophysiology. Pronounced
variation in subunit-selectivity, potency, and agonist efficacy was observed in a
manner that was dependent on the GluN2 subunit in the NMDA receptor. In
particular, compounds 15a and 16a are potent GluN2C-specific superagonists at the
GluN1 subunit with agonist efficacies of 398% and 308% compared to glycine. This
study demonstrates that subunit-selectivity among glycine site NMDA receptor
agonists can be achieved and suggests that glycine-site agonists can be developed
as pharmacological tool compounds to study GluN2C-specific effects in NMDA
receptor-mediated neurotransmission.
PMID- 28514143
TI - Community-Level Sanitation Coverage More Strongly Associated with Child Growth
and Household Drinking Water Quality than Access to a Private Toilet in Rural
Mali.
AB - Sanitation access can provide positive externalities; for example, safe disposal
of feces by one household prevents disease transmission to households nearby.
However, little empirical evidence exists to characterize the potential health
benefits from sanitation externalities. This study investigated the effect of
community sanitation coverage versus individual household sanitation access on
child health and drinking water quality. Using a census of 121 villages in rural
Mali, we analyzed the association of community latrine coverage (defined by a 200
m radius surrounding a household) and individual household latrine ownership with
child growth and household stored water quality. Child height-for-age had a
significant and positive linear relationship with community latrine coverage,
while child weight-for-age and household water quality had nonlinear
relationships that leveled off above 60% coverage (p < 0.01; generalized additive
models). Child growth and water quality were not associated with individual
household latrine ownership. The relationship between community latrine coverage
and child height was strongest among households without a latrine; for these
households, each 10% increase in latrine coverage was associated with a 0.031 (p
value = 0.040) increase in height-for-age z-score. In this study, the level of
sanitation access of surrounding households was more important than private
latrine access for protecting water quality and child health.
PMID- 28514144
TI - Water Purification Using Functionalized Cellulosic Fibers with Nonleaching
Bacteria Adsorbing Properties.
AB - Portable purification systems are easy ways to obtain clean drinking water when
there is no large-scale water treatment available. In this study, the potential
to purify water using bacteria adsorbing cellulosic fibers, functionalized with
polyelectrolytes according to the layer-by-layer method, is investigated. The
adsorbed polyelectrolytes create a positive charge on the fiber surface that
physically attracts and bonds with bacteria. Three types of cellulosic materials
have been modified and tested for the bacterial removal capacity in water. The
time, material-water ratio and bacterial concentration dependence, as well as the
bacterial removal capacity in water from natural sources, have been evaluated.
Freely dispersed bacteria adsorbing cellulosic fibers can remove greater than
99.9% of Escherichia coli from nonturbid water, with the most notable reduction
occurring within the first hour. A filtering approach using modified cellulosic
fibers is desirable for purification of natural water. An initial filtration test
showed that polyelectrolyte multilayer modified cellulosic fibers can remove
greater than 99% of bacteria from natural water. The bacteria adsorbing
cellulosic fibers do not leach any biocides, and it is an environmentally
sustainable and cheap option for disposable water purification devices.
PMID- 28514145
TI - Versatile Construction of 6-Substituted cis-2,8-Dioxabicyclo[3.3.0]octan-3-ones:
Short Enantioselective Total Syntheses of Cheloviolenes A and B and Dendrillolide
C.
AB - A short enantioselective synthesis of 6-substituted cis-2,8
dioxabicyclo[3.3.0]octan-3-ones is described. The pivotal step is coupling of a
tertiary radical generated directly from a tertiary alcohol with a 3-chloro-5
alkoxybutenolide. This strategy is applied toward scalable 14-15 step syntheses
of three rearranged spongian diterpenoids: cheloviolenes A and B and
dendrillolide C.
PMID- 28514146
TI - Accuracy of Explicitly Correlated Local PNO-CCSD(T).
AB - In recent years PNO-based local correlation methods have gained popularity since
they allow Coupled Cluster (CC) calculations with reduced computational costs,
yet only a few systematic studies concerning their accuracy are available, in
particular for the explicitly correlated versions. In this work we take a deeper
look at the explicitly correlated local PNO-CCSD(F12*)(T0) and PNO-CCSD(F12*)(T)
methods. The first variant uses the so-called semicanonical triples correction
(T0) which neglects off-diagonal elements in the occupied block of the Fock
matrix. In PNO-CCSD(F12*)(T) this approximation is avoided by means of Laplace
transformation techniques and convergence to the canonical results in the limit
of no PNO truncation is restored. We assess the accuracy of both methods using
well established benchmark sets for reaction energies and weak molecular
interactions and take a look at a system with strong cooperative many-body
effects. For reaction energies a close agreement with canonical methods is
observed, and chemical accuracy can be reached. Also for weak intermolecular
interactions the accuracy is easily controlled, and the methods even allow for
improving existing benchmark data.
PMID- 28514147
TI - Fragmentation of Valence and Core-Shell (Cl 2p) Excited C2Cl4 Molecule.
AB - The dynamics of the photofragmentation pathways of tetrachloroethylene with
photon energies from 15 up to 250 eV encompassing the Cl 2p edge is presented. In
order to distinguish the fragmentation channels, the ionic fragments were
separated according to their mass-to-charge ratio, measured in coincidence with
the photoelectrons, and collected as a function of the incident photon energy.
Distinct minima or maxima are found in the partial ion yield in the region
between 40 and 50 eV. These features are believed to be associated with the
Cooper minimum which results from a molecular orbital with a strong atomic 3p
subshell character. In the shallow core region, some fragmentation patterns are
considered in terms of fast fragmentation of the C2Cl4 molecule, despite the
heavy mass of its fragments. In the present case, the fast fragmentation is
favored by the very strong antibonding character of the LUMO, understandable in
the frame of the core equivalent model for halogen-containing molecules. In
addition, ab initio calculations were performed to obtain states at the Cl 2p
edge. Singlet and triplet states at the Cl 2p edge of the C2Cl4 molecule,
corresponding to the Cl(2p -> 9b1u*) and Cl(2p -> 8b2u*) transitions, were
calculated in order to form a basis set of molecular states from which the spin
orbit splitting can be inferred. Multiconfigurational self-consistent field
(MCSCF) calculation followed by multireference configuration interaction (MRCI)
was the method chosen to establish a set of singlet and triplet states at the 2p
excitation edge in addition to the ground state.
PMID- 28514148
TI - Hirsutane-Type Sesquiterpenes with Inhibitory Activity of Microglial Nitric Oxide
Production from the Red Alga-Derived Fungus Chondrostereum sp. NTOU4196.
AB - The marine red alga Pterocladiella capillacea is an economic alga for the food
industry in Taiwan, and its associated highly diversified fungi have not been
investigated meticulously thus far. The EtOAc extract of the fermented broth of
Chondrostereum sp. NTOU4196, a fungal strain isolated from P. capillacea, was
found to exhibit significant nitric oxide (NO) production inhibitory activity in
lipopolysaccharide-activated murine RAW 264.7 cells at a concentration of 100
MUg/mL in the preliminary screening. Therefore, separation of the active
principles from the fermented broths was performed, and that has led to the
isolation of eight new 5,5,5-tricyclic hirsutane-type sesquiterpenes, namely,
chondroterpenes A-H (1-8), together with seven known analogues. They were
identified by analyses of spectroscopic data and comparison with literature
values. Among the new isolates, chondroterpene A (1) exhibited more significant
NO production inhibitory activity in murine BV-2 microglial cells, and of all the
isolated compounds, hirsutanol A (9) exerted limited cytotoxic effects and the
most potent inhibitory activity on NO production.
PMID- 28514149
TI - Structural and Optical Properties of Subporphyrinoids: A TD-DFT Study.
AB - Using ab initio approaches accounting for environmental effects, we investigate
the ground- and excited-state properties of four subporphyrinoids: subporphyrin,
subporphyrazine, tribenzosubporphyrin, and subphthalocyanine. We first show that
the selected level of theory, that is DFT(PBE0), is able to reproduce the
structure and NMR spectra of all compounds. The aromaticity of these four
macrocyclic entities are next quantified and it is showed that these bowl-shape
induced molecules present very strong aromatic characters. Next we analyze the
spectral signatures of all four compounds using an approach going beyond the
vertical approximation. The 0-0 energies are reproduced with a mean absolute
deviation smaller than 0.1 eV, and the very good agreement obtained between
experimental and theoretical band shapes allows us to unravel the vibronic
contributions responsible to the specific band shapes of these subporphyrinoids.
Finally, we investigate a large series of substituted subporphyrins, demonstrate
the quality of the trends that are obtained with theory and design new compounds
presenting red-shifted optical bands.
PMID- 28514150
TI - Correction to "Photocycle of Photoactive Yellow Protein in Cell-Mimetic
Environments: Molecular Volume Changes and Kinetics".
PMID- 28514151
TI - DeepPPI: Boosting Prediction of Protein-Protein Interactions with Deep Neural
Networks.
AB - The complex language of eukaryotic gene expression remains incompletely
understood. Despite the importance suggested by many proteins variants
statistically associated with human disease, nearly all such variants have
unknown mechanisms, for example, protein-protein interactions (PPIs). In this
study, we address this challenge using a recent machine learning advance-deep
neural networks (DNNs). We aim at improving the performance of PPIs prediction
and propose a method called DeepPPI (Deep neural networks for Protein-Protein
Interactions prediction), which employs deep neural networks to learn effectively
the representations of proteins from common protein descriptors. The experimental
results indicate that DeepPPI achieves superior performance on the test data set
with an Accuracy of 92.50%, Precision of 94.38%, Recall of 90.56%, Specificity of
94.49%, Matthews Correlation Coefficient of 85.08% and Area Under the Curve of
97.43%, respectively. Extensive experiments show that DeepPPI can learn useful
features of proteins pairs by a layer-wise abstraction, and thus achieves better
prediction performance than existing methods. The source code of our approach can
be available via http://ailab.ahu.edu.cn:8087/DeepPPI/index.html .
PMID- 28514153
TI - Efficient DLPNO-CCSD(T)-Based Estimation of Formation Enthalpies for C-, H-, O-,
and N-Containing Closed-Shell Compounds Validated Against Critically Evaluated
Experimental Data.
AB - An accurate and cost-efficient methodology for the estimation of the enthalpies
of formation for closed-shell compounds composed of C, H, O, and N atoms is
presented and validated against critically evaluated experimental data. The
computational efficiency is achieved through the use of the resolution-of
identity (RI) and domain-based local pair-natural orbital coupled cluster (DLPNO
CCSD(T)) approximations, which results in a drastic reduction in both the
computational cost and the number of necessary steps for a composite quantum
chemical method. The expanded uncertainty for the proposed methodology evaluated
using a data set of 45 thoroughly vetted experimental values for molecules
containing up to 12 heavy atoms is about 3 kJ.mol-1, competitive with those of
typical calorimetric measurements. For the compounds within the stated scope, the
methodology is shown to be superior to a representative, more general, and widely
used composite quantum chemical method, G4.
PMID- 28514152
TI - Hepatoprotective Properties of a Polyphenol-Enriched Fraction from Annona
crassiflora Mart. Fruit Peel against Diabetes-Induced Oxidative and Nitrosative
Stress.
AB - A polyphenol-enriched fraction from Annona crassiflora fruit peel (Ac-Pef)
containing chlorogenic acid, (epi)catechin, procyanidin B2, and caffeoyl
glucoside was investigated against hepatic oxidative and nitrosative stress in
streptozotocin-induced diabetic rats. Serum biochemical parameters, hepatic
oxidative and nitrosative status, glutathione defense system analysis, and in
silico assessment of absorption, distribution, metabolism, excretion, and
toxicity (ADMET) of the main compounds of Ac-Pef were carried out. Ac-Pef
treatment during 30 days decreased serum alanine aminotransferase, aspartate
aminotransferase, and alkaline phosphatase activities, as well as hepatic lipid
peroxidation, protein carbonylation and nitration, inducible nitric oxide
synthase level, and activities and expressions of glutathione peroxidase,
superoxide dismutase, and catalase. There were increases in antioxidant capacity,
glutathione reductase activity, and reduced glutathione level. ADMET predictions
of Ac-Pef compounds showed favorable absorption and distribution, with no
hepatotoxicity. A. crassiflora fruit peel showed hepatoprotective properties,
indicating a promising natural source of bioactive molecules for prevention and
therapy of diabetes complications.
PMID- 28514154
TI - Au-Catalyzed [2 + 3] Annulation of Enamides with Propargyl Esters: Total
Synthesis of Cephalotaxine and Cephalezomine H.
AB - A novel Au-catalyzed [2 + 3] annulation reaction of enamides with propargyl
esters has been developed, providing a new method for expeditious assembly of
synthetically useful functionalized 1-azaspiro[4.4]nonane building blocks. Based
on this key annulation, strategic installation of the pivotal azaspirocyclic
core, followed by constructing the benzazepine unit via Witkop cyclization, led
to the divergent total syntheses of cephalotaxine and cephalezomine H.
PMID- 28514155
TI - Influence of Monomer Connectivity, Network Flexibility, and Hydrophobicity on the
Hydrothermal Stability of Organosilicas.
AB - It is generally assumed that the hydrothermal stability of organically modified
silica networks is promoted by high monomer connectivity, network flexibility,
and the presence of hydrophobic groups in the network. In this study a range of
organosilica compositions is synthesized to explore the extent to which these
factors play a role in the hydrothermal dissolution of these materials.
Compositions were synthesized from hexafunctional organically bridged
silsesquioxanes (OR1)3Si-R-Si(OR1)3 (R = -CH2-, -C2H4-, -C6H12-, -C8H16-, -p-C6H4
; R1 = -CH3, -C2H5), tetrafunctional (OEt)2Si(CH3)-C2H4-Si(CH3)(OEt)2 and
Si(OEt)4, trifunctional silsesquioxanes R'-Si(OMe)3 (R'=CH3, n-C3H7, cyclo-C6H11,
phenyl), and bifunctional Si(i-C3H7)2(OMe)2. The bond strain, connectivity and
hydroxyl concentration of all networks were estimated using 29Si cross-polarized
magic angle spinning nuclear magnetic resonance and Fourier-transform infrared
spectroscopy. The hydrophilicity was characterized by monitoring the water uptake
of the materials in moisture treatments with thermogravimetric analysis,
differential scanning calorimetry, and Fourier-transform infrared spectroscopy.
The resistance of each network against hydrothermal dissolution in a water/1,5
pentanediol mixture at 80 degrees C and pH 1, 7, and 13 was analyzed with
inductively coupled plasma optical emission spectroscopy and X-ray fluorescence.
Bond strain appears to significantly increase the tendency to dissolve under
hydrothermal conditions. The stabilizing influences of increased connectivity and
hydrophobicity were found to be weak.
PMID- 28514156
TI - Self-Assembly, Hydrogelation, and Nanotube Formation by Cation-Modified
Phenylalanine Derivatives.
AB - Fluorenylmethoxycarbonyl-protected phenylalanine (Fmoc-Phe) derivatives are a
privileged class of molecule that spontaneously self-assemble into hydrogel
fibril networks. Fmoc-Phe-derived hydrogels are typically formed by dilution of
the hydrogelator from an organic cosolvent into water, by dissolution of the
hydrogelator under basic aqueous conditions followed by adjustment of the pH with
acid, or by other external triggering forces, including sonication and heating.
These conditions complicate biological applications of these hydrogels. Herein,
we report C-terminal cation-modified Fmoc-Phe derivatives that are positively
charged across a broad range of pH values and that can self-assemble and form
hydrogel networks spontaneously without the need to adjust pH or to use an
organic cosolvent. In addition, these cationic Fmoc-Phe derivatives are found to
self-assemble into novel sheet-based nanotube structures at higher
concentrations. These nanotube structures are unique to C-terminal cationic Fmoc
Phe derivatives; the parent Fmoc-Phe carboxylic acids form only fibril or worm
like micelle structures. Nanotube formation by the cationic Fmoc-Phe molecules is
dependent on positive charge at the C-terminus, since at basic pH where the
positive charge is reduced only fibrils/worm-like micelles are formed and
nanotube formation is suppressed. These studies provide an important example of
Fmoc-Phe derivatives that can elicit hydrogelation without organic cosolvent or
pH modification and also provide insight into how subtle modification of
structure can perturb the self-assembly pathways of Fmoc-Phe derivatives.
PMID- 28514158
TI - Preparation of Carbon Dots for Cellular Imaging by the Molecular Aggregation of
Cellulolytic Enzyme Lignin.
AB - Carbon dots, which are less than 10 nm in diameter, have been widely investigated
because of their unique luminescence properties and potential for use in
bioimaging. In the present work, natural carbon dots (L-CDs) were obtained by
molecular aggregation, using ethanol-extracted cellulolytic enzyme lignin. The
whole process for the preparation of L-CDs was green and simple to operate and
did not use toxic chemical reagents or harsh conditions. The newly prepared L-CDs
emitted multicolor photoluminescence following one- and two-photon excitation.
The L-CDs also showed good cellular biocompatibility, which is crucial for
biological applications. One- and two-photon cell-imaging studies demonstrated
the potential of L-CDs for bioimaging.
PMID- 28514157
TI - Polymersomes with Rapid K+-Triggered Drug-Release Behaviors.
AB - A novel type of smart polymersomes with rapid K+-triggered drug-release
properties is developed in this work. Block copolymers with biocompatible
poly(ethylene glycol) (PEG) as the hydrophilic block and poly(N
isopropylacrylamide-co-benzo-18-crown-6-acrylamide) (PNB) copolymer as the K+
responsive block are successfully synthesized. Because of the presence of 18
crown-6 units, the PEG-b-PNB block copolymers exhibit excellent K+-dependent
phase-transition behaviors, which show a hydrophilic-hydrophobic state in
simulated extracellular fluid and present a hydrophilic-hydrophilic state in
simulated intracellular fluid. Polymersomes with regular spherical shape and good
monodispersity are prepared by the self-assembly of the PEG-b-PNB block
copolymers. Both hydrophilic fluorescein isothiocyanate-dextran and hydrophobic
doxorubicin are selected as model drugs and are successfully encapsulated into
the PEG-b-PNB polymersomes. After being placed in a simulated intracellular fluid
with high K+ concentration, the PEG-b-PNB polymersomes immediately disassemble
accompanied by the rapid and complete release of drugs. Such K+-responsive
polymersomes with the desired drug-release properties provide a novel strategy
for advanced intracellular drug delivery and release, which can enhance the
safety and efficacy of cancer therapy.
PMID- 28514159
TI - Direct Observation of an Efficient Triplet Exciton Diffusion Process in a
Platinum-Containing Conjugated Polymer.
AB - We report the synthesis and characterization of a conjugated polymer incorporated
with cyclometalated platinum complexes on the main chain. The polymer may serve
as an efficient triplet sensitizer in light-harvesting systems. The photophysical
properties of the polymer were studied by nanosecond and femtosecond time
resolved transient absorption spectroscopies. After excitation, an energy
transfer process from the thiophene units on the conjugated main chain to the
singlet excited state of the Pt complex moieties occurred in less than 150 fs.
The subsequent intersystem crossing process resulted in the formation of a
triplet excited state at the Pt complex moieties in ~3.2 ps, which was then
followed by an efficient triplet diffusion process that led to the formation of
triplet excitons on the polymer main chain in ~283 ps. This proposed efficient
triplet sensitized polymer system not only enhances the exciton diffusion length
but also reduces energy loss in the process, which displays remarkable
implications in the design of novel materials for triplet sensitized solar cells.
PMID- 28514160
TI - Spatiotemporal Observation of Electron-Impact Dynamics in Photovoltaic Materials
Using 4D Electron Microscopy.
AB - Understanding light-triggered charge carrier dynamics near photovoltaic-material
surfaces and at interfaces has been a key element and one of the major challenges
for the development of real-world energy devices. Visualization of such dynamics
information can be obtained using the one-of-a-kind methodology of scanning
ultrafast electron microscopy (S-UEM). Here, we address the fundamental issue of
how the thickness of the absorber layer may significantly affect the charge
carrier dynamics on material surfaces. Time-resolved snapshots indicate that the
dynamics of charge carriers generated by electron impact in the electron-photon
dynamical probing regime is highly sensitive to the thickness of the absorber
layer, as demonstrated using CdSe films of different thicknesses as a model
system. This finding not only provides the foundation for potential applications
of S-UEM to a wide range of devices in the fields of chemical and materials
research, but also has impact on the use and interpretation of electron beam
induced current for optimization of photoactive materials in these devices.
PMID- 28514162
TI - Diastereoselective and Branched-Aldehyde-Selective Tandem Hydroformylation
Hemiaminal Formation: Synthesis of Functionalized Piperidines and Amino Alcohols.
AB - Starting from readily available allylglycine, a tandem hydroformylation
hemiaminal formation reaction has been developed for the synthesis of chiral
functionalized piperidines, with very good diastereoselectivity and branched
regioselectivity using Rh/(S,S,S)-BOBPHOS catalysts. Tandem hydroformylation
hemiacetal formation also proceeds with good diastereoselectivity (88:12), with
the hemiacetal product being hydrogenated with retention of stereochemistry to
give a chiral intermediate used in the synthesis of the new antibiotic
nemonoxacin.
PMID- 28514161
TI - Interdiffusion Reaction-Assisted Hybridization of Two-Dimensional Metal-Organic
Frameworks and Ti3C2Tx Nanosheets for Electrocatalytic Oxygen Evolution.
AB - Two-dimensional (2D) metal-organic framework (MOF) nanosheets have been recently
regarded as the model electrocatalysts due to their porous structure, fast mass
and ion transfer through the thickness, and large portion of exposed active metal
centers. Combining them with electrically conductive 2D nanosheets is anticipated
to achieve further improved performance in electrocatalysis. In this work, we in
situ hybridized 2D cobalt 1,4-benzenedicarboxylate (CoBDC) with Ti3C2Tx (the
MXene phase) nanosheets via an interdiffusion reaction-assisted process. The
resulting hybrid material was applied in the oxygen evolution reaction and
achieved a current density of 10 mA cm-2 at a potential of 1.64 V vs reversible
hydrogen electrode and a Tafel slope of 48.2 mV dec-1 in 0.1 M KOH. These results
outperform those obtained by the standard IrO2-based catalyst and are comparable
with or even better than those achieved by the previously reported state-of-the
art transition-metal-based catalysts. While the CoBDC layer provided the highly
porous structure and large active surface area, the electrically conductive and
hydrophilic Ti3C2Tx nanosheets enabled the rapid charge and ion transfer across
the well-defined Ti3C2Tx-CoBDC interface and facilitated the access of aqueous
electrolyte to the catalytically active CoBDC surfaces. The hybrid nanosheets
were further fabricated into an air cathode for a rechargeable zinc-air battery,
which was successfully used to power a light-emitting diode. We believe that the
in situ hybridization of MXenes and 2D MOFs with interface control will provide
more opportunities for their use in energy-based applications.
PMID- 28514163
TI - Palladium-Catalyzed alpha-Stereoselective O-Glycosylation of O(3)-Acylated
Glycals.
AB - Pd(MeCN)2Cl2 enables the alpha-stereoselective catalytic synthesis of 2,3
unsaturated O-glycosides from O(3)-acylated glycals without the requirement for
additives to preactivate either donor or nucleophile. Mechanistic studies suggest
that, unlike traditional (eta3-allyl)palladium-mediated processes, the reaction
proceeds via an alkoxy-palladium intermediate that increases the proton acidity
and oxygen nucleophilicity of the alcohol. The method is exemplified with the
synthesis of a range of glycosides and glycoconjugates of synthetic utility.
PMID- 28514165
TI - Hydrophobic alpha,alpha-Disubstituted Disilylated TESDpg Induces Incipient 310
Helix in Short Tripeptide Sequence.
AB - To evaluate the contribution of triethylsilyl alpha,alpha-di-n-propylglycine,
namely TESDpg, to induce a defined secondary structure, we have prepared model
tripeptides in which TESDpg was inserted in three different positions. Studies in
solid state and in solution with adapted techniques showed that TESDpg was able
to induce a nascent 310 helix in both crystal and solution states.
PMID- 28514166
TI - A Web Service Framework for Interactive Analysis of Metabolomics Data.
AB - Analyzing mass spectrometry-based metabolomics data presents a major challenge to
metabolism researchers, as it requires downloading and processing large data
volumes through complex "pipelines", even in cases where only a single metabolite
or peak is of interest. This presents a significant hurdle for data sharing,
reanalysis, or meta-analysis of existing data sets, whether locally stored or
available from public repositories. Here we introduce mzAccess, a software system
that provides interactive, online access to primary mass spectrometry data in
real-time via a Web service protocol, circumventing the need for bulk data
processing. mzAccess allows querying instrument data for spectra, chromatograms,
or two-dimensional MZ-RT areas in either profile or centroid modes through a
simple, uniform interface that is independent of vendor or instrument type. Using
a cache mechanism, mzAccess achieves response times in the millisecond range for
typical liquid chromatography-mass spectrometry (LC-MS) peaks, enabling real-time
browsing of large data sets with hundreds or even thousands of samples. By
simplifying access to metabolite data, we hope that this system will help enable
data sharing and reanalysis in the metabolomics field.
PMID- 28514164
TI - The Nonbulky DNA Lesions Spiroiminodihydantoin and 5-Guanidinohydantoin
Significantly Block Human RNA Polymerase II Elongation in Vitro.
AB - The most common, oxidatively generated lesion in cellular DNA is 8-oxo-7,8
dihydroguanine, which can be oxidized further to yield highly mutagenic
spiroiminodihydantoin (Sp) and 5-guanidinohydantoin (Gh) in DNA. In human cell
free extracts, both lesions can be excised by base excision repair and global
genomic nucleotide excision repair. However, it is not known if these lesions can
be removed by transcription-coupled DNA repair (TCR), a pathway that clears
lesions from DNA that impede RNA synthesis. To determine if Sp or Gh impedes
transcription, which could make each a viable substrate for TCR, either an Sp or
a Gh lesion was positioned on the transcribed strand of DNA under the control of
a promoter that supports transcription by human RNA polymerase II. These
constructs were incubated in HeLa nuclear extracts that contained active RNA
polymerase II, and the resulting transcripts were resolved by denaturing
polyacrylamide gel electrophoresis. The structurally rigid Sp strongly blocks
transcription elongation, permitting 1.6 +/- 0.5% nominal lesion bypass. In
contrast, the conformationally flexible Gh poses less of a block to human RNAPII,
allowing 9 +/- 2% bypass. Furthermore, fractional lesion bypass for Sp and Gh is
minimally affected by glycosylase activity found in the HeLa nuclear extract.
These data specifically suggest that both Sp and Gh may well be susceptible to
TCR because each poses a significant block to human RNA polymerase II
progression. A more general principle is also proposed: Conformational
flexibility may be an important structural feature of DNA lesions that enhances
their transcriptional bypass.
PMID- 28514168
TI - Regioselective Carbyne Transfer to Ring-Opening Alkyne Metathesis Initiators
Gives Access to Telechelic Polymers.
AB - Regioselective carbyne-transfer reagents derived from (3,3,3-trifluoroprop-1-yn-1
yl)benzene give access to functionalized ring-opening alkyne metathesis
polymerization (ROAMP) initiators [R-C6H4C=Mo(OC(CH3)(CF3)2)3] featuring electron
donating or -withdrawing substituents on the benzylidyne. Kinetic studies and
linear free-energy relationships reveal that the initiation step of the ring
opening alkyne metathesis polymerization of 5,6,11,12
tetradehydrobenzo[a,e][8]annulene exhibits a moderate positive Hammett reaction
constant (rho = +0.36). ROAMP catalysts featuring electron-withdrawing
benzylidynes not only selectively increase the rate of initiation (ki) over the
rate of propagation (kp) but also prevent undesired intra- and intermolecular
chain-transfer processes, giving access to linear poly-(o-phenylene ethynylene)
with narrow molecular weight distribution. The regioselective carbyne transfer
methodology and the detailed mechanistic insight enabled the design of a
bifunctional ROAMP-reversible addition-fragmentation chain-transfer (RAFT)
initiator complex. ROAMP followed by RAFT polymerization yields hybrid poly-(o
phenylene ethynylene)-block-poly-(methyl acrylate) block copolymers.
PMID- 28514169
TI - Engineering Interface Structure to Improve Efficiency and Stability of
Organometal Halide Perovskite Solar Cells.
AB - The rapid rise of power conversion efficiency (PCE) of low cost organometal
halide perovskite solar cells suggests that these cells are a promising
alternative to conventional photovoltaic technology. However, anomalous
hysteresis and unsatisfactory stability hinder the industrialization of
perovskite solar cells. Interface engineering is of importance for the
fabrication of highly stable and hysteresis free perovskite solar cells. Here we
report that a surface modification of the widely used TiO2 compact layer can give
insight into interface interaction in perovskite solar cells. A highest PCE of
18.5% is obtained using anatase TiO2, but the device is not stable and degrades
rapidly. With an amorphous TiO2 compact layer, the devices show a prolonged
lifetime but a lower PCE and more pronounced hysteresis. To achieve a high PCE
and long lifetime simultaneously, an insulating polymer interface layer is
deposited on top of TiO2. Three polymers, each with a different functional group
(hydroxyl, amino, or aromatic group), are investigated to further understand the
relation of interface structure and device PCE as well as stability. We show that
it is necessary to consider not only the band alignment at the interface, but
also interface chemical interactions between the thin interface layer and the
perovskite film. The hydroxyl and amino groups interact with CH3NH3PbI3 leading
to poor PCEs. In contrast, deposition of a thin layer of polymer consisting of an
aromatic group to prevent the direct contact of TiO2 and CH3NH3PbI3 can
significantly enhance the device stability, while the same time maintaining a
high PCE. The fact that a polymer interface layer on top of TiO2 can enhance
device stability, strongly suggests that the interface interaction between TiO2
and CH3NH3PbI3 plays a crucial role. Our work highlights the importance of
interface structure and paves the way for further optimization of PCEs and
stability of perovskite solar cells.
PMID- 28514170
TI - Discovery of Novel 11-Triazole Substituted Benzofuro[3,2-b]quinolone Derivatives
as c-myc G-Quadruplex Specific Stabilizers via Click Chemistry.
AB - The specificity of nucleic acids' binders is crucial for developing this kind of
drug, especially for novel G-quadruplexes' binders. Quindoline derivatives have
been developed as G-quadruplex stabilizers with good interactive activities. In
order to improve the selectivity and binding affinity of quindoline derivatives
as c-myc G-quadruplex binding ligands, novel triazole containing
benzofuroquinoline derivatives (T-BFQs) were designed and synthesized by using
the 1,3-dipolar cycloaddition of a series of alkyne and azide building blocks.
The selectivity toward c-myc G-quadruplex DNA of these novel T-BFQs was
significantly improved, together with an obvious increase on binding affinity.
Further cellular and in vivo experiments indicated that the T-BFQs showed
inhibitory activity on tumor cells' proliferation, presumably through the down
regulation of transcription of c-myc gene. Our findings broadened the
modification strategies of specific G-quadruplex stabilizers.
PMID- 28514171
TI - Selective Aerobic C-H Amination of Phenols with Primary Amines over Copper toward
Benzoxazoles.
AB - Using O2 as the oxidant, the benzoxazole frameworks can be directly constructed
from the readily available phenols and primary amines in the presence of NH4PF6
over copper under mild conditions. Mechanistic studies showed that a novel
mechanism involving biphenyldiols and o-quinones very possibly takes effect in
the reaction, because both can selectively give the benzoxazoles under the
reaction conditions. An unprecedented unstrained Caryl-Caryl bond cleavage takes
place in the reaction.
PMID- 28514167
TI - Quantum Dot-Peptide-Fullerene Bioconjugates for Visualization of in Vitro and in
Vivo Cellular Membrane Potential.
AB - We report the development of a quantum dot (QD)-peptide-fullerene (C60) electron
transfer (ET)-based nanobioconjugate for the visualization of membrane potential
in living cells. The bioconjugate is composed of (1) a central QD electron donor,
(2) a membrane-inserting peptidyl linker, and (3) a C60 electron acceptor. The
photoexcited QD donor engages in ET with the C60 acceptor, resulting in quenching
of QD photoluminescence (PL) that tracks positively with the number of C60
moieties arrayed around the QD. The nature of the QD-capping ligand also
modulates the quenching efficiency; a neutral ligand coating facilitates greater
QD quenching than a negatively charged carboxylated ligand. Steady-state
photophysical characterization confirms an ET-driven process between the donor
acceptor pair. When introduced to cells, the amphiphilic QD-peptide-C60
bioconjugate labels the plasma membrane by insertion of the peptide-C60 portion
into the hydrophobic bilayer, while the hydrophilic QD sits on the exofacial side
of the membrane. Depolarization of cellular membrane potential augments the ET
process, which is manifested as further quenching of QD PL. We demonstrate in
HeLa cells, PC12 cells, and primary cortical neurons significant QD PL quenching
(DeltaF/F0 of 2-20% depending on the QD-C60 separation distance) in response to
membrane depolarization with KCl. Further, we show the ability to use the QD
peptide-C60 probe in combination with conventional voltage-sensitive dyes (VSDs)
for simultaneous two-channel imaging of membrane potential. In in vivo imaging of
cortical electrical stimulation, the optical response of the optimal QD-peptide
C60 configuration exhibits temporal responsivity to electrical stimulation
similar to that of VSDs. Notably, however, the QD-peptide-C60 construct displays
20- to 40-fold greater DeltaF/F0 than VSDs. The tractable nature of the QD
peptide-C60 system offers the advantages of ease of assembly, large DeltaF/F0,
enhanced photostability, and high throughput without the need for complicated
organic synthesis or genetic engineering, respectively, that is required of
traditional VSDs and fluorescent protein constructs.
PMID- 28514172
TI - Synthesis of Gold Nanoparticles Using the Interface of an Emulsion Droplet.
AB - A facile and rapid method for synthesizing single crystal gold spherical or
platelet (nonspherical) particles is reported. The reaction takes place at the
interface of two immiscible liquids where the reducing agent decamethylferrocene
(DmFc) was initially added to hexane and gold chloride (AuCl4-) to an aqueous
phase. The reaction is spontaneous at room temperature, leading to the creation
of Au nanoparticles (AuNP). A flow focusing microfluidic chip was used to create
emulsion droplets, allowing the same reaction to take place within a series of
microreactors. The technique allows the number of droplets, their diameter, and
even the concentration of reactants in both phases to be controlled. The size and
shape of the AuNP are dependent upon the concentration of the reactants and the
size of the droplets. By tuning the reaction parameters, the synthesized
nanoparticles vary from nanometer to micrometer sized spheres or platelets. The
surfactant used to stabilize the emulsion was also shown to influence the
particle shape. Finally, the addition of other nanoparticles within the droplet
allows for core@shell particles to be readily formed, and we believe this could
be a versatile platform for the large scale production of core@shell particles.
PMID- 28514173
TI - Rh(III)-Catalyzed Regio- and Chemoselective [4 + 1]-Annulation of Azoxy Compounds
with Diazoesters for the Synthesis of 2H-Indazoles: Roles of the Azoxy Oxygen
Atom.
AB - A Rh(III)-catalyzed tandem C-H alkylation/intramolecular decarboxylative
cyclization of azoxy compounds with diazoesters for the synthesis of 3-acyl-2H
indazoles is disclosed. The azoxy instead of the azo group enables a distinct
approach for cyclative capture, leading to a [4 + 1]-annulation rather than a
classic [4 + 2] manner. The azoxy oxygen atom is traceless after annulation, and
further removal from the product is not required. This reaction features a
complete regioselectivity for unsymmetrical azoxybenzenes and a compatibility of
monoaryldiazene oxides.
PMID- 28514174
TI - Implications of Occupational Disorder on Ion Mobility in Li4Ti5O12 Battery
Materials.
AB - Lithium-titanium-oxide (Li4Ti5O12, LTO) is unique among battery materials due to
its exceptional cyclability and high rate capability. This performance is
believed to derive at least partly from the occupational disorder introduced via
mixed Li/Ti occupancy in the LTO spinel-like structure. We explore the vast
configuration space accessible during high-temperature LTO synthesis by Monte
Carlo sampling and indeed find lowest-energy structures to be characterized by a
high degree of microscopic inhomogeneity. Dynamical simulations in corresponding
configurations reveal the dominant fraction of Li ions to be immobile on
nanosecond time scales. However, Ti antisite-like defects stabilized by the
configurational disorder give rise to a novel correlated ion diffusion mechanism.
The resulting fast but localized diffusion could be a key element in the sudden
rise in conductivity found in LTO in the early stages of charging and questions
the validity of ion mobility measurements for this and other configurationally
disordered materials.
PMID- 28514175
TI - Hybrid Model Membrane Combining Micropatterned Lipid Bilayer and Hydrophilic
Polymer Brush.
AB - Substrate-supported planar lipid bilayers (SPBs) are being utilized as a
versatile model system of the biological membrane. However, the proximity between
the solid support and membrane limits utility of SPBs for the functional analyses
of membrane proteins. Here, we present a model membrane that can enlarge the
distance between the substrate surface and the membrane by combining a stable
scaffold of polymerized lipid bilayer with a hydrophilic polymer brush. A
micropatterned SPB was generated by the lithographic polymerization of
diacetylene lipids and subsequent incorporation of natural (fluid) lipid
bilayers. Hydrophilic polymer brush of poly-2-methacryloyloxyethyl
phosphorylcholine (poly(MPC)) was formed on the surface of polymeric bilayer by
the in situ atom transfer radical polymerization (ATRP) in aqueous solution, in
the presence of embedded fluid lipid bilayers. A model membrane protein
(Haloquadratum walsbyi bacteriorhodopsin: HwBR) could be reconstituted into the
polymer brush-supported bilayers with significantly reduced immobile molecules.
Furthermore, the polymer brush terminals could be functionalized by successively
polymerizing MPC and 2-aminoethyl methacrylate (AMA). The reactive amine moiety
of poly(AMA) enables to conjugate a wide range of biological molecules and
surfaces to the membrane. The combination of micropatterned bilayer and polymer
brush mimics the two- and three-dimensional structures of the biological
membrane, providing a platform to assay membrane proteins in a truly biomimetic
environment.
PMID- 28514176
TI - Transition-Metal-Free, Visible-Light-Enabled Decarboxylative Borylation of Aryl N
Hydroxyphthalimide Esters.
AB - Herein, we report a conceptually novel borylation reaction proceeding via a mild
photoinduced decarboxylation of redox-activated aromatic carboxylic acids. This
work constitutes the first application of cheap and easily prepared N
hydroxyphthalimide esters as aryl radical precursors and does not require the use
of expensive transition metals or ligands. The reaction is operationally simple,
scalable, and displays broad scope and functional group tolerance.
PMID- 28514177
TI - Rh(III)-Catalyzed [4 + 1]-Annulation of Azoxy Compounds with Alkynes: A
Regioselective Approach to 2H-Indazoles.
AB - A rhodium-catalyzed regioselective C-H activation/cyclization of azoxy compounds
with alkynes has been disclosed to construct a variety of 2H-indazoles. A [4 + 1]
cycloaddition rather than a normal [4 + 2] mode is observed in the process of
cyclative capture along with an oxygen-atom transfer and a C=C triple bond
cleavage. This protocol features a broad substrate scope, a good functional group
tolerance, and an exclusive regioselectivity.
PMID- 28514178
TI - Defect-Mediated Electron-Hole Separation in One-Unit-Cell ZnIn2S4 Layers for
Boosted Solar-Driven CO2 Reduction.
AB - The effect of defects on electron-hole separation is not always clear and is
sometimes contradictory. Herein, we initially built clear models of two
dimensional atomic layers with tunable defect concentrations, and hence directly
disclose the defect type and distribution at atomic level. As a prototype,
defective one-unit-cell ZnIn2S4 atomic layers are successfully synthesized for
the first time. Aberration-corrected scanning transmission electron microscopy
directly manifests their distinct zinc vacancy concentrations, confirmed by
positron annihilation spectrometry and electron spin resonance analysis. Density
functional calculations reveal that the presence of zinc vacancies ensures higher
charge density and efficient carrier transport, verified by ultrafast
photogenerated electron transfer time of ~15 ps from the conduction band of
ZnIn2S4 to the trap states. Ultrafast transient absorption spectroscopy manifests
the higher zinc vacancy concentration that allows for ~1.7-fold increase in
average recovery lifetime, confirmed by surface photovoltage spectroscopy and PL
spectroscopy analysis, which ensures promoted carrier separation rates. As a
result, the one-unit-cell ZnIn2S4 layers with rich zinc vacancies exhibit a
carbon monoxide formation rate of 33.2 MUmol g-1 h-1, roughly 3.6 times higher
than that of the one-unit-cell ZnIn2S4 layers with poor zinc vacancies, while the
former's photocatalytic activity shows negligible loss after 24 h photocatalysis.
This present work uncovers the role of defects in affecting electron-hole
separation at atomic level, opening new opportunities for achieving highly
efficient solar CO2 reduction performances.
PMID- 28514179
TI - Two-Incision Laparoscopic Cholecystectomy: Reducing Scars in a Simple Way.
AB - BACKGROUND: About 20% of the population has cholelithiasis and this is the main
abdominal cause of hospitalization in developed countries. Considering that only
in the United States about 700,000 cholecystectomies are done each year, it is
possible to estimate the importance of the problem for public health. OBJECTIVE:
To describe a two-incision laparoscopic cholecystectomy (TILC) technique using
only conventional material, without increasing complications or operative time.
MATERIALS AND METHODS: A consecutive and prospective case series compared to
another historical operated by conventional laparoscopic cholecystectomy (LC).
The TILC was performed with three trocars in two incisions, two trocars in
umbilical incision, and one in epigastrium. RESULTS: A total of 72 patients were
operated on by the same surgeon (36 in each group). There were no significant
differences between groups for gender, mean age, body mass index, or length of
hospital stay. The procedures were classified by the surgeon according to
surgical difficulty and 58.3% (n = 42) were considered low grade, 9.7% (n = 7)
difficult, and the other were intermediaries, with no difference between the
series (P < .05). There were minor complications in 6.94% (n = 5) procedures.
There were no differences between mean operative time (P = .989), which was 49
(95% confidence interval [CI] 42-56) minutes in LC and 40 (95% CI 35-44) min in
TILC. There was no need for additional trocars in any case or for conversion to
open surgery. CONCLUSIONS: TILC is feasible, safe, and with good aesthetic
result, using the same instruments of LC, without increasing operative time.
PMID- 28514180
TI - Molecular Typing of Vibrio parahaemolyticus Strains Isolated from Mollusks in the
North Adriatic Sea.
AB - BACKGROUND: Vibrio parahaemolyticus is an emerging foodborne pathogen in the
Mediterranean, usually associated with shellfish consumption. The increase in the
number of outbreaks in Europe is primarily associated with the global warming of
the ocean that has a great impact on the spread and genetic selection of
waterborne pathogens. The primary role of Italy in Europe's mollusk production,
together with the fact that cases of infections with V. parahaemolyticus are not
always notified to the European community, highlighted the necessity of acquiring
new information about the epidemiological involvement of shellfish products.
OBJECTIVE: The aim of the study was to provide useful insights into the first
steps of the Risk Assessment associated with V. parahaemolyticus through the
molecular characterization of isolates from commercialized mollusks. MATERIALS
AND METHODS: A total of 102 strains identified as V. parahaemolyticus were
investigated as part of a larger sampling (1-year survey) from several shellfish
species collected from the Venice lagoon and the North Adriatic sea. All strains
were characterized by multilocus sequence typing and tested for the presence of
virulence genes (trh and tdh). The study of sampling/environmental factors and
epidemiological analyses was performed to describe the behaviors of the different
genetic populations. RESULTS: The population structure analysis highlighted three
genetic clusters that could be subject to temperature selection during cold (<=15
degrees C) and warm (>16 degrees C) seasons. Moreover, other factors, such as
molluscan species (clams/mussels), probably played a role in the distribution of
genetic clusters. Although few strains carried the virulence factors (n = 6
trh+), epidemiological links with clinical isolates and a local dissemination of
some sequence types were underlined. CONCLUSION: This work provides a useful
background on the genotype spread as a first step in the Hazard Identification in
light of future climate changes.
PMID- 28514181
TI - Folic Acid Modulates DMBA/TPA-Induced Changes in Skin of Mice: A Study Relevant
to Carcinogenesis.
AB - The present study was aimed at investigating the modulatory effects of folic acid
(FA) on early stages of chemically induced skin cancer. For this, a two-stage
model of skin tumorigenesis was employed. 7,12-Dimethylbenz(a)anthracene (DMBA,
500 nmol/100 ul of acetone) was applied topically for two weeks (twice weekly),
followed by phorbol-12-myristate-13-acetate (TPA, 1.7 nmol/100 ul) twice weekly
for six weeks on the depilated skin of mice, and FA was administered orally at a
dose of 40 microgram/animal for 10 weeks daily. Balb/c mice were divided into
four groups depending upon the treatment they received (control, DMBA/TPA, FA,
and FA+DMBA/TPA). DMBA/TPA treatment led to the formation of papillomas in
DMBA/TPA and FA+DMBA/TPA groups. Ornithine decarboxylase (ODC), proliferating
cell nuclear antigen (PCNA), epidermal thickness, and cell count were evaluated
to assess the beneficial effects in the early stages. FA exhibited its
ameliorative potential as indicated by decreased epidermal thickness and cell
count in FA+DMBA/TPA group when compared to DMBA/TPA group. Concomitantly, FA
decreased the expression of ODC and PCNA in skin and activity of serum lactate
dehydrogenase, suggesting inhibitory effects on cell proliferation and cell
damage. Differential modulation in lipid peroxidation and reduced glutathione was
observed in response to DMBA/TPA treatment and its intervention with FA. Although
these findings suggest the inhibitory potential of FA during initial stages of
murine skin cancer, detailed studies are warranted considering the ambiguous
reports available in literature regarding the association of FA and cancer.
PMID- 28514182
TI - Aberrant Level of Skp2 and p27KIP1 in Intraductal Proliferative Lesions is
Associated with Tumorigenesis.
AB - Breast cancer is one of the leading causes of cancer-related death in women
worldwide. Here we aimed to examine the expression status of S-phase kinase
associated protein 2 (Skp2) and p27KIP1, and assess the significance of Skp2 plus
p27KIP1 expression in patients with intraductal proliferative lesions, including
ductal carcinoma in situ (DCIS) and atypical ductal hyperplasia (ADH). Skp2 and
p27KIP1 mRNA levels in DCIS, ADH, flat epithelial atypia, and usual ductal
hyperplasia (UDH) were evaluated by quantitative real-time reverse transcription
polymerase chain reaction and protein expression was evaluated
immunohistochemically in 60 fresh tissues and 120 paraffin-embedded tissues from
patients with the four subtypes above. We found that the protein and mRNA level
of Skp2 were significantly increased in DCIS and ADH as compared with that in
UDH. In contrast, p27KIP1 protein and mRNA levels were reduced. Based on the
above findings, abnormal levels of Skp2 and p27KIP1 have probably been involved
in the pathogenesis of ADH and DCIS. Thus, Skp2 and p27KIP1 may serve as
important diagnosis markers.
PMID- 28514184
TI - Maintenance Lenalidomide for Large-Cell Lymphoma: Who Really Benefits?
PMID- 28514183
TI - Multigene Panel Testing Provides a New Perspective on Lynch Syndrome.
AB - Purpose Most existing literature describes Lynch syndrome (LS) as a hereditary
syndrome leading to high risks of colorectal cancer (CRC) and endometrial cancer
mainly as a result of mutations in MLH1 and MSH2. Most of these studies were
performed on cohorts with disease suggestive of hereditary CRC and population
based CRC and endometrial cancer cohorts, possibly biasing results. We aimed to
describe a large cohort of mismatch repair (MMR) mutation carriers ascertained
through multigene panel testing, evaluate their phenotype, and compare the
results with those of previous studies. Methods We retrospectively reviewed
clinical histories of patients who had multigene panel testing, including the MMR
and EPCAM genes, between March 2012 and June 2015 (N = 34,981) and performed a
series of statistical comparisons. Results Overall, MSH6 mutations were most
frequent, followed by PMS2, MSH2, MLH1, and EPCAM mutations, respectively. Of 528
patients who had MMR mutations, 63 (11.9%) had breast cancer only and 144 (27.3%)
had CRC only. When comparing those with breast cancer only to those with CRC
only, MSH6 and PMS2 mutations were more frequent than MLH1 and MSH2 mutations ( P
= 2.3 * 10-5). Of the 528 patients, 22.2% met BRCA1 and BRCA2 ( BRCA1/2) testing
criteria and not LS criteria, and 5.1% met neither BRCA1/2 nor LS testing
criteria. MSH6 and PMS2 mutations were more frequent than MLH1 and MSH2 mutations
among patients who met BRCA1/2 testing criteria but did not meet LS testing
criteria ( P = 4.3 * 10-7). Conclusion These results provide a new perspective on
LS and suggest that individuals with MSH6 and PMS2 mutations may present with a
hereditary breast and ovarian cancer phenotype. These data also highlight the
limitations of current testing criteria in identifying these patients, as well as
the need for further investigation of cancer risks in patients with MMR
mutations.
PMID- 28514185
TI - Acute treatment of migraine: quo vadis?
PMID- 28514187
TI - Diphenhydramine inhibits voltage-gated proton channels (Hv1) and induces
acidification in leukemic Jurkat T cells- New insights into the pro-apoptotic
effects of antihistaminic drugs.
AB - An established characteristic of neoplastic cells is their metabolic
reprogramming, known as the Warburg effect, with greater reliance on
energetically less efficient pathways (such as glycolysis and pentose phosphate
shunt) compared with oxidative phosphorylation. This results in an overproduction
of acidic species that must be extruded to maintain intracellular homeostasis. We
recently described that blocking the proton currents in leukemic cells mediated
by Hv1 ion channels triggers a marked intracellular acidification and apoptosis
induction. Moreover, histamine H1-receptor antagonists were found to induce
apoptosis in tumoral cells but the mechanism is still unclear. By using Jurkat T
cells, we now show how diphenhydramine inhibits Hv1 mediated currents, inducing a
drop in intracellular pH and cellular viability. This provides evidence of a new
target structure responsible of the known pro-apoptotic action of antihistaminic
drugs.
PMID- 28514186
TI - APC/C-Cdc20 mediates deprotection of centromeric cohesin at meiosis II in yeast.
AB - Cells undergoing meiosis produce haploid gametes through one round of DNA
replication followed by 2 rounds of chromosome segregation. This requires that
cohesin complexes, which establish sister chromatid cohesion during S phase, are
removed in a stepwise manner. At meiosis I, the separase protease triggers the
segregation of homologous chromosomes by cleaving cohesin's Rec8 subunit on
chromosome arms. Cohesin persists at centromeres because the PP2A phosphatase,
recruited by the shugoshin protein, dephosphorylates Rec8 and thereby protects it
from cleavage. While chromatids disjoin upon cleavage of centromeric Rec8 at
meiosis II, it was unclear how and when centromeric Rec8 is liberated from its
protector PP2A. One proposal is that bipolar spindle forces separate PP2A from
Rec8 as cells enter metaphase II. We show here that sister centromere
biorientation is not sufficient to "deprotect" Rec8 at meiosis II in yeast.
Instead, our data suggest that the ubiquitin-ligase APC/CCdc20 removes PP2A from
centromeres by targeting for degradation the shugoshin Sgo1 and the kinase Mps1.
This implies that Rec8 remains protected until entry into anaphase II when it is
phosphorylated concurrently with the activation of separase. Here, we provide
further support for this model and speculate on its relevance to mammalian
oocytes.
PMID- 28514188
TI - The Invisibility of Mild Traumatic Brain Injury: Impaired Cognitive Performance
as a Silent Symptom.
AB - The present study was designed to tackle two notorious features of mild traumatic
brain injury (mTBI)-heterogeneity and invisibility-by characterizing the full
scope of mTBI symptoms. Mice were exposed to brain injuries of different
intensities utilizing a weight-drop model (10, 30, 50, and 70 g) and subsequently
subjected to a comprehensive battery of behavioral tests at different time points
and immunohistochemical examination of cortical slices. Whereas the
physiological, neurological, emotional, and motor function of mTBI mice (i.e.,
their well-being) remained largely intact, cognitive deficits were identified by
the y-maze and novel object recognition. Results from these two cognitive tests
were combined and a dose-response relationship was established between injury
intensity and cognitive impairment, ranging from an 85% decline after a 70-g
impact (p < 0.001) to a 20% decline after a 10-g impact (essentially no effect).
In addition, higher intensities of injury were accompanied by decreased
expression of axonal and synaptic markers. Thus, our mTBI mice showed a clear
discrepancy between performance (poor cognitive function) and appearance (healthy
demeanor). This is of major concern given that diagnosis of mTBI is established
on the presence of clinical symptoms and emphasizes the need for an alternative
diagnostic modality.
PMID- 28514189
TI - Effects of Vaccination with the C-Strain Vaccine on Immune Cells and Cytokines of
Pigs Against Classical Swine Fever Virus.
AB - The attenuated C-strain vaccine against classical swine fever virus (CSFV) is one
of the safest and most effective attenuated vaccines. However, little is known of
the host immune response after vaccination with the C-strain vaccine. Blood
samples from vaccinated pigs were collected to evaluate the number of immune
cells, the level of specific CSFV antibody, and related cytokines induced by the
vaccination of C-strain vaccine. The C-strain nucleic acid was gradually removed
and specific antibody to vaccine kept increasing; the amount of the lymphocyte,
Tc cell, and Th cell increased; some inflammatory cytokines such as interleukin
(IL)-1 and tumor necrosis factor-alpha mainly showed downregulated trends, but IL
6 and IL-8 were upregulated greatly; IL-2, IL-4, IL-5, IL-12p40, IL-13,
interferon (IFN)-I, and Toll-like receptors (TLRs) kept high expression level
after 28 days postvaccination (dpv); IFN-gamma was upregulated slightly at 5 and
9 dpv, respectively. These results suggest that the C-strain vaccine induces a
Th2 cell response to produce the specific antibody. The vaccine virus replicates
at very low level. C-strain vaccine burden has close relationship with the
expression of TLRs. The overexpression of TLRs initiates the innate immune system
to clear up the vaccine. Meanwhile, ILs expressed by immune system induce the
differentiation of B cells and produce specific antibody.
PMID- 28514191
TI - Commentary on Some Recent Theses Relevant to Combating Aging: June 2017.
PMID- 28514190
TI - Criterion-Referenced Fitness Standards Associated with Maintaining Functional
Capacity in Chilean Older Adults.
AB - The aim of the current study was to develop fitness standards associated with
maintaining physical capacity in older adults at two different levels-that needed
for advanced functioning and that needed for maintaining moderate (independent)
functional ability. This was a cross-sectional study of 406 Chilean adults aged
60 and more. Functional capacity was measured through the Composite Physical
Function (CPF) scale. A battery of validated fitness tests for this population
was used. Based on the results of the CPF, two variables were created: "advanced
physical capacity" (defined as those scoring 24 on the CPF scale) and "moderate
(independent) physical capacity," defined as those scoring between 14 and 23 on
the CPF scale. Fitness cut-off values were calculated for each of the two created
variables to evaluate the risk of losing the independence through Receiver
Operating Characteristic (ROC) curves analysis and logistic regression. The
developed cut-off points provide important information for professionals working
directly with older adults, to detect the risk of losing functionality and
independence.
PMID- 28514192
TI - Diagnostic and Treatment Patterns Among Children, Adolescents, and Young Adults
with Thyroid Cancer in Ontario: 1992-2010.
AB - BACKGROUND: Thyroid carcinoma is rare in young children, with a sharp increase in
incidence among adolescents and young adults between 15 and 29 years of age. The
incidence of thyroid carcinoma is increasing worldwide. Limited prospective
population-based data are available to describe diagnostic and treatment
practices in this age group. This study undertook a population-based review of
thyroid carcinoma among 0- to 29-year-old individuals in Ontario, Canada,
utilizing linked administrative data to describe the demographic and care
patterns over nearly two decades. METHODS: Cases from the Ontario Cancer Registry
were identified and linked to administrative data sources at the Institute for
Clinical Evaluative Sciences. Cases diagnosed prior to a patient's 30th birthday
between 1992 and 2010 were considered eligible. Billing records identified
ultrasonography, fine-needle aspiration biopsy, radioiodine therapy, and surgical
approach. RESULTS: A total of 2552 patients aged 0-29 years were diagnosed with
thyroid carcinoma during the study period. There was a 2.1-fold increase in
standardized incidence rate over the 19 years of this study. Thyroid carcinoma
was diagnosed subsequent to a prior malignancy in 47/2552 patients at a median
interval of 11.6 years after initial cancer diagnosis. Seventeen individuals
developed a second malignancy after treatment for thyroid carcinoma. Most
patients (90.44%) underwent preoperative ultrasound (ranging from 1 to 13
preoperative studies). Preoperative thyroid scintigraphy was used in 44% of
patients, with a significant decline in usage over the study period. Fine-needle
aspiration biopsy usage rose by 20% over the study period, although 26% of
patients had no biopsy prior to surgery. Primary total thyroidectomy followed by
two-stage thyroidectomy were the most frequently performed procedures, and 56% of
patients received therapeutic radioiodine. CONCLUSIONS: This study establishes a
foundation of diagnostic and practice patterns over nearly two decades. The study
corroborates, in the Ontario population, the rising incidence of thyroid
carcinoma in children and adolescents and young adults. Finally, it identifies
the use of multiple preoperative ultrasound studies, low rates of thyroid biopsy,
and thyroid scintigraphy as targets to improve efficiencies of care and to reduce
unnecessary healthcare expenditures through education, standardization of
diagnostic approach, and possibly regionalization of care.
PMID- 28514195
TI - Analysis of the Use and Impact of Twitter During American Society of Clinical
Oncology Annual Meetings From 2011 to 2016: Focus on Advanced Metrics and User
Trends.
AB - PURPOSE: The use of social media, in particular Twitter, has substantially
increased among health care stakeholders in the field of hematology and oncology,
with an especially sharp increase in the use of Twitter during times of major
national meetings. The most attended meeting in the oncology field is the ASCO
annual meeting. Little is known about the detailed metrics involved in the use,
volume, and impact of Twitter during the ASCO annual meeting. METHODS: We
conducted a retrospective review of tweets during the ASCO annual meetings from
2011 to 2016. The total data set encompassed 190,732 tweets from 39,745 authors
over six consecutive ASCO meetings from 2011 to 2016 (inclusive). Tweets, all
publically available, were collected by Nephrology On-Demand Analytics. RESULTS:
The number of individual authors increased from 1,429 during the 2011 ASCO
meeting to 15,796 during the 2016 ASCO meeting, an 11-fold increase over the
total 5-year period. There was a notable increase in tweets from the 2011 ASCO
meeting (n = 7,746) to the 2016 ASCO meeting (n = 72,698), a nine-fold increase
during the study period. The most commonly tweeted term or topic changed over
time, generally reflecting the breakthroughs of each designated year; these terms
were "melanoma" for both the 2011 and 2012 ASCO meetings; "breast cancer" for the
2013 ASCO meeting; "lung cancer" for the 2014 ASCO meeting; and "ImmunOnc" or
"immunotherapy/immuno-oncology" for both the 2015 and 2016 ASCO meetings.
CONCLUSION: The use of Twitter among health care stakeholders during the ASCO
meeting has markedly increased over time, demonstrating the increasing role of
social media in the dissemination of findings at the most highly attended
hematology and oncology conference of the year.
PMID- 28514196
TI - Interactions Between NS1 of Influenza A Viruses and Interferon-alpha/beta:
Determinants for Vaccine Development.
AB - Influenza A viruses (IAVs) cause mild to severe infections in humans with
considerable socioeconomic and global health consequences. The host interferon
(IFN)-alpha/beta response, critical as the first line of defense against foreign
pathogens, is induced upon detection of IAV genomic RNA in infected cells by host
innate pattern recognition receptors. IFN-alpha/beta production and subsequent
activation of cell signaling result in the expression of antiviral IFN-stimulated
genes whose products target various stages of the IAV life cycle to inhibit viral
replication and the spread of infection and establish an antiviral state. IAVs,
however, encode a multifunctional virulence factor, nonstructural protein 1
(NS1), that directly antagonizes the host IFN-alpha/beta response to support
viral replication. In this review, we highlight the mechanisms by which NS1
suppresses IFN-alpha/beta production and subsequent cell signaling, and consider,
therefore, the potential for recombinant IAVs lacking NS1 to be used as live
attenuated vaccines.
PMID- 28514193
TI - 90-90-90-Plus: Maintaining Adherence to Antiretroviral Therapies.
AB - Medication adherence is the "Plus" in the global challenge to have 90% of HIV
infected individuals tested, 90% of those who are HIV positive treated, and 90%
of those treated achieve an undetectable viral load. The latter indicates viral
suppression, the goal for clinicians treating people living with HIV (PLWH). The
comparative importance of different psychosocial scales in predicting the level
of antiretroviral adherence, however, has been little studied. Using data from a
cross-sectional study of medication adherence with an international convenience
sample of 1811 PLWH, we categorized respondent medication adherence as None (0%),
Low (1-60%), Moderate (61-94%), and High (95-100%) adherence based on self
report. The survey contained 13 psychosocial scales/indices, all of which were
correlated with one another (p < 0.05 or less) and had differing degrees of
association with the levels of adherence. Controlling for the influence of race,
gender, education, and ability to pay for care, all scales/indices were
associated with adherence, with the exception of Berger's perceived stigma scale.
Using forward selection stepwise regression, we found that adherence self
efficacy, depression, stressful life events, and perceived stigma were
significant predictors of medication adherence. Among the demographic variables
entered into the model, nonwhite race was associated with double the odds of
being in the None rather than in the High adherence category, suggesting these
individuals may require additional support. In addition, asking about self
efficacy, depression, stigma, and stressful life events also will be beneficial
in identifying patients requiring greater adherence support. This support is
essential to medication adherence, the Plus to 90-90-90.
PMID- 28514197
TI - Change of Serum IgG4 in Patients with Ocular Adnexal Marginal Zone B Cell
Lymphoma Associated with IgG4-Related Ophthalmic Disease After Treatment.
AB - PURPOSE: To investigate the change of serum IgG4 concentrations correlated with
clinical evolution in patients with ocular adnexal marginal zone B cell lymphoma
associated with IgG4-related ophthalmic disease (IgG4-ROD). METHODS: Three
consecutive patients with histopathologically confirmed ocular adnexal marginal
zone B cell lymphoma associated with IgG4-ROD were evaluated. Two patients
received radiotherapy and 1 patient received steroid therapy. Treatment outcome
was evaluated by clinical symptoms, radiologic examination, and change of serum
IgG4 level in these patients. RESULTS: All patients had elevated serum IgG4
before treatment (462, 338, and 780 mg/dL respectively.) The 2 patients who
received radiotherapy achieved complete remission and the serum IgG4 decreased to
345 and 92 mg/dL, respectively. The patient who underwent systemic steroid
achieved partial remission and the serum IgG4 decrease to 161 mg/dL. CONCLUSION:
Our study showed elevated serum IgG4 in all patients with ocular adnexal marginal
zone B cell lymphoma associated with IgG4-ROD. In addition, the elevated serum
IgG4 may decrease or keep stable after treatment, accompanied by improvement in
clinical symptoms and reduction of lesions.
PMID- 28514199
TI - Drawing asthma: An exploration of patients' perceptions and experiences.
AB - OBJECTIVE: As an art form, drawings can facilitate the tangible expression of
patients' inner images and feelings in a range of health conditions. However,
there are currently no published studies investigating adults' perspectives of
asthma using drawings. This study aimed to explore how adults' drawings
illustrate their perceptions and experiences of asthma. METHODS: Adults with
asthma participated in a one-on-one drawing activity. Analysis was grounded in
the participants' accounts of their drawing, which were examined alongside the
relevant image. A coding approach was used to cluster thematic material and map
the data according to the Common-Sense Model of Self-Regulation (CSM). RESULTS:
Eighteen participants took part. Three themes emerged: (1) asthma is constrictive
and restrictive, (2) feeling alone, feeling different, and (3) the life journey
of asthma. The drawings aligned with several domains of the CSM, in particular
consequences. The images drawn by the participants and their subsequent
discussions highlighted the prominence of the emotional burden of asthma.
CONCLUSIONS: The drawings provided powerful and evocative communication of the
experience of asthma. Future research using drawings can further both healthcare
professionals' and patients' understanding of the physical, social and emotional
demands of living with asthma, and support the development of asthma self
management practices.
PMID- 28514198
TI - Piceatannol Reduces Fat Accumulation in Caenorhabditis elegans.
AB - Excess fat accumulation and abnormal metabolism are involved in numerous diseases
and thus the research on identification of compounds that can regulate energy
homeostasis could significantly facilitate the current effort to prevent and/or
treat metabolic disorders. Piceatannol, one of the natural stilbenes, was
previously found to decrease lipid accumulation of 3T3-L1 adipocytes. However,
its role in fat metabolism in vivo is not known. Thus, Caenorhabditis elegans as
an animal model was used in the current study to determine the effect of
piceatannol on fat accumulation and its underlying mechanisms. The results showed
that 50 and 100 MUM piceatannol significantly reduced fat accumulation of wild
type worms grown in normal and high-glucose conditions without altering the
growth rate, worm length, pumping rate, or moving speed. The current study
further indicated that piceatannol decreased the expression of sbp-1 (encodes an
ortholog of mammalian sterol regulatory element-binding protein) and its target
gene fasn-1 (encodes an ortholog of fatty acid synthase) as well as increased the
expression of hosl-1 (encodes an ortholog of hormone-sensitive lipase) in glucose
treated worms. These data suggested that piceatannol reduced fat accumulation in
C. elegans by suppression of genes involved in lipid synthesis and possibly
through stimulation of lipolysis. Given that piceatannol exerts similar effects
in both C. elegans and 3T3-L1 cells, our finding could provide a mechanistic
insight into the role of piceatannol in lipid metabolism in mammals.
PMID- 28514200
TI - Culturally Competent Sexual Healthcare as a Prerequisite for Obtaining
Preexposure Prophylaxis: Findings from a Qualitative Study.
AB - PURPOSE: Men who have sex with men (MSM) experience stigma in healthcare
settings, which impedes disclosure of sexual behavior, potentially limiting
uptake of preexposure prophylaxis (PrEP). The purpose of this study was to
describe the context of this limitation and explore geographical variability.
METHODS: To understand how discomfort in healthcare settings affects PrEP
utilization, we conducted two online focus groups with geographically diverse
samples of MSM. RESULTS: Respondents identified primary care providers as
preferred sources for PrEP, but potential uptake was limited by barriers to
establishing nonjudgmental relationships with these providers. CONCLUSION:
Improved patient-provider communication about sexual behaviors might increase
PrEP use among MSM.
PMID- 28514202
TI - The physical characteristics of match-play in English schoolboy and academy rugby
union.
AB - The aim was to compare the physical characteristics of under-18 academy and
schoolboy rugby union competition by position (forwards and backs). Using a
microsensor unit, match characteristics were recorded in 66 players. Locomotor
characteristics were assessed by maximum sprint speed (MSS) and total, walking,
jogging, striding and sprinting distances. The slow component (<2 m . s-1) of
PlayerLoadTM (PLslow), which is the accumulated accelerations from the three axes
of movement, was analysed as a measure of low-speed activity (e.g., rucking). A
linear mixed-model was assessed with magnitude-based inferences. Academy forwards
and backs almost certainly and very likely covered greater total distance than
school forwards and backs. Academy players from both positions were also very
likely to cover greater jogging distances. Academy backs were very likely to
accumulate greater PLslow and the academy forwards a likely greater sprinting
distance than school players in their respective positions. The MSS, total,
walking and sprinting distances were greater in backs (likely-almost certainly),
while forwards accumulated greater PLslow (almost certainly) and jogging distance
(very likely). The results suggest that academy-standard rugby better prepares
players to progress to senior competition compared to schoolboy rugby.
PMID- 28514204
TI - Factors influencing influenza vaccination among South Korean adult asthma
patients: A nationwide population-based cross-sectional study.
AB - BACKGROUND: It is important to identify factors associated with influenza
vaccination. This study was performed to investigate factors associated with
vaccination coverage among asthma patients in Korea. METHODS: Data were obtained
from 229,121 participants (5,989 with asthma and 223,132 without asthma) in the
2010 Korean Community Health Survey. The demographic characteristics and
socioeconomic status of respondents with and without asthma were compared.
Univariate and multiple logistic regression analyses were used to evaluate
socioeconomic status and other demographic variables potentially related to
influenza vaccination in asthma patients. RESULTS: The vaccination rates of young
(19-49 years) and middle-aged (50-64 years) asthma patients were only 28.3 and
49.5%, respectively, whereas that of elderly (>=65 years) asthma patients was
81.5%. After regression, older age (odds ratio [OR], 5.53; 95% confidence
interval [95% CI], 3.56-8.59), poor self-rated health status (OR, 1.43; 95% CI,
1.01-2.03), and regular health check-ups (OR, 2.07, 95% CI, 1.64-2.60) were
associated with increased influenza vaccination rates in asthma patients.
CONCLUSIONS: It is important to improve influenza vaccination coverage for non
elderly patients with asthma, especially those who do not engage in regular
exercise or undergo regular health check-ups and those who consider themselves to
be healthy.
PMID- 28514205
TI - APJ Is Associated with Treatment Response in Gastric Cancer Patients Receiving
Concurrent Chemoradiotherapy and Endostar Therapy.
AB - BACKGROUND: Endostar combined with concurrent chemoradiotherapy (CRT) has been
used in patients with gastric cancers (GCs). However, there are no reliable
markers to predict the treatment response and prognosis of these patients. Apelin
and its receptor (APJ) are involved in angiogenesis in tumor tissues. We aimed to
study whether Apelin and Apelin receptor (APJ) tumor expression can predict the
treatment response of combination therapy of endostar and CRT. MATERIALS AND
METHODS: We enrolled patients with locally advanced GC receiving CRT only and
CRT+endostar combination therapy. Apelin receptor (APJ) in tumor samples was
determined by immunohistological staining and scored by measuring staining area
and signal intensity. RESULTS: The high APJ expression has significantly higher
rates of tumor invasion, local lymph node, and distant metastasis (all p <
0.001). In the CRT only group, the distribution of high and low APJ expression in
patients with good and poor treatment response to CRT is not significantly
different (p = 0.235). However, in the CRT+endostar group, the chance of having
poor response to combined treatment is 3.645-fold higher in those having high APJ
expression levels than those who have low APJ expression levels. Our prognostic
analysis shows that in the CRT+endostar group, high APJ expression had
significantly shorter overall survival (OS) period than those with low APJ
expression (p < 0.001). Furthermore, multivariate survival analysis reveals that
the APJ expression is an independent predictor for the OS period in GC patients
treated with CRT+endostar. CONCLUSION: Tumor APJ can be used to predict the
therapy response and prognosis in GC patients receiving CRT+endostar therapy.
PMID- 28514203
TI - Cost-effectiveness of MR Imaging-guided Strategies for Detection of Prostate
Cancer in Biopsy-Naive Men.
AB - Purpose To evaluate the cost-effectiveness of multiparametric diagnostic magnetic
resonance (MR) imaging examination followed by MR imaging-guided biopsy
strategies in the detection of prostate cancer in biopsy-naive men presenting
with clinical suspicion of cancer for the first time. Materials and Methods A
decision-analysis model was created for biopsy-naive men who had been recommended
for prostate biopsy on the basis of abnormal digital rectal examination results
or elevated prostate-specific antigen levels (age groups: 41-50 years, 51-60
years, and 61-70 years). The following three major strategies were evaluated: (a)
standard transrectal ultrasonography (US)-guided biopsy; (b) diagnostic MR
imaging followed by MR imaging-targeted biopsy, with no biopsy performed if MR
imaging findings were negative; and (c) diagnostic MR imaging followed by MR
imaging-targeted biopsy, with a standard biopsy performed when MR imaging
findings were negative. The following three MR imaging-guided biopsy strategies
were further evaluated in each MR imaging category: (a) biopsy with cognitive
guidance, (b) biopsy with MR imaging/US fusion guidance, and (c) in-gantry MR
imaging-guided biopsy. Model parameters were derived from the literature. The
primary outcome measure was net health benefit (NHB), which was measured as
quality-adjusted life-years (QALYs) gained or lost by investing resources in a
new strategy compared with a standard strategy at a willingness-to-pay (WTP)
threshold of $50 000 per QALY gained. Probabilistic sensitivity analysis was
performed by using Monte Carlo simulations. Results Noncontrast MR imaging
followed by cognitively guided MR biopsy (no standard biopsy if MR imaging
findings were negative) was the most cost-effective approach, yielding an
additional NHB of 0.198 QALY compared with the standard biopsy approach.
Noncontrast MR imaging followed by in-gantry MR imaging-guided biopsy (no
standard biopsy if MR imaging findings were negative) led to the highest NHB gain
of 0.251 additional QALY compared with the standard biopsy strategy. All MR
imaging strategies were cost-effective in 94.05% of Monte Carlo simulations.
Analysis by age groups yielded similar results. Conclusion MR imaging-guided
strategies for the detection of prostate cancer were cost-effective compared with
the standard biopsy strategy in a decision-analysis model. (c) RSNA, 2017 Online
supplemental material is available for this article.
PMID- 28514206
TI - First-in-Human PET/CT Imaging of Metastatic Neuroendocrine Neoplasms with
Cyclotron-Produced 44Sc-DOTATOC: A Proof-of-Concept Study.
AB - 44Sc is a promising positron emission tomography (PET) radionuclide (T1/2 = 4.04
hours, Ebeta+average = 632 keV) and can be made available, using a cyclotron
production route, in substantial quantities as a highly pure product. Herein, the
authors report on a first-in-human PET/CT study using 44Sc-DOTATOC prepared with
cyclotron-produced 44Sc. The production of 44Sc was carried out through the
44Ca(p,n)44Sc nuclear reaction at Paul Scherrer Institut, Switzerland. After
separation, 44Sc was shipped to Zentralklinik Bad Berka, Germany, where
radiolabeling was performed, yielding radiochemically pure 44Sc-DOTATOC. Two
patients, currently followed up after peptide receptor radionuclide therapy of
metastatic neuroendocrine neoplasms, participated in this proof-of-concept study.
Blood sampling was performed before and after application of 44Sc-DOTATOC. PET/CT
acquisitions, performed at different time points after injection of 44Sc-DOTATOC,
allowed detection of even very small lesions on delayed scans. No clinical
adverse effects were observed and the laboratory hematological, renal, and
hepatic profiles remained unchanged. In this study, cyclotron-produced 44Sc was
used in the clinic for the first time. It is attractive for theranostic
application with 177Lu, 90Y, or 47Sc as therapeutic counterparts. 44Sc-based
radiopharmaceuticals will be of particular value for PET facilities without
radiopharmacy, to which they can be shipped from a centralized production site.
PMID- 28514207
TI - Circadian Gene CLOCK Affects Drug-Resistant Gene Expression and Cell
Proliferation in Ovarian Cancer SKOV3/DDP Cell Lines Through Autophagy.
AB - Abnormal autophagy regulation affects the chemoresistance of ovarian cancer,
during which the circadian gene clock may play a major role. In this study, RNA
interference plasmid pSUPER-Clock and overexpression plasmid pcDNA3.1-Clock of
CLOCK were used to stably transfect the SKOV3/DDP cells by lipofection. Upon
screening, the in vitro transfected cell lines with pSUPER-Clock, the autophagy
level, and G0/G1 phase cells were significantly reduced, and the expression
levels of Clock, LC3, P-gp, and MRP2 were inhibited. In contrast, the autophagy
level and G0/G1 phase cells in cell lines transfected with pcDNA3.1-Clock were
significantly increased, and the expressions of Clock, LC3, P-gp, and MRP2 were
enhanced. In comparison with the untransfected control group showed the
percentage of apoptotic cells in SKOV3/DDP cell lines of Clock interfering
expression group after cisplatin treatment was significantly increased while the
survival was substantially reduced. These results indicated that inhibiting the
circadian gene Clock expression can reverse the cisplatin resistance of ovarian
cancer SKOV3/DDP cell lines by affecting the protein expression of drug
resistance genes during which autophagy plays an important role. The CLOCK gene
may be designated as a novel candidate for targeted gene therapy in drug
resistant ovarian cancer.
PMID- 28514208
TI - Clinical Significance and Tumor-Suppressive Function of miR-516b in Nonsmall Cell
Lung Cancer.
AB - BACKGROUND: MicroRNA-516b (miR-516b) has been recently reported to be
downregulated in nonsmall cell lung cancer (NSCLC). However, its clinical
significance and biological function in NSCLC remain to be clarified. MATERIALS
AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used
to detect the expression of miR-516b in 82 paired fresh primary tumor tissues and
NSCLC cell lines. The association of miR-516b expression with clinicopathological
factors and prognosis was statistically analyzed by SPSS 21.0 software, Kaplan
Meier method, and Cox regression analyses. Cell Counting Kit-8, colony formation,
flow cytometric, Transwell migration, and invasion assays were used to evaluate
the proliferation, cell cycle, apoptosis, migration, and invasion of NSCLC cells
after miR-516b mimics or negative control of mimics transfection. RESULTS: The
expression level of miR-516b was found to be significantly lower in NSCLC tissues
and cell lines than in corresponding normal tissues and cells. Decreased miR-516b
expression was significantly associated with tumor size (p = 0.004), Tumor Node
Metastasis (TNM) stage (p = 0.016), and shorter overall survival (p = 0.0039).
Multivariate analysis suggested that miR-516b was an independent risk factor for
NSCLC (hazard ratio = 2.435, 95% confidence interval: 1.423-2.457; p = 0.003).
Furthermore, overexpression of miR-516b could inhibit NSCLC cell proliferation,
cell cycle progression, migration and invasion, and promoted cell apoptosis. The
qRT-PCR results indicated that overexpressing miR-516b reduced the mRNA
expression of CDK2, MMP-2, and MMP-9, whereas increased BAX mRNA expression in
NSCLC cells. Their protein expression levels presented similar trends, as
confirmed by Western blotting. CONCLUSIONS: Findings in this study demonstrated
for the first time that miR-516b expression might be a novel diagnostic and
prognostic factor, as well as a promising target for NSCLC.
PMID- 28514209
TI - Cancer Biotherapy: More Than Immunotherapy.
PMID- 28514210
TI - Systemic Effects of Local Tumor Ablation: Oncogenesis and Antitumor Induced
Immunity.
PMID- 28514211
TI - Diagnostic Performance of Self-navigated Whole-Heart Contrast-enhanced Coronary 3
T MR Angiography.
PMID- 28514212
TI - Dynamic Contrast-enhanced MR Imaging of Advanced Hepatocellular Carcinoma:
Comparison with the Liver Parenchyma and Correlation with the Survival of
Patients Receiving Systemic Therapy.
PMID- 28514213
TI - Liver Surface Nodularity as a Biomarker for Detection and Evaluation of
Cirrhosis.
PMID- 28514214
TI - Imaging of Acute Capsuloligamentous Sports Injuries in the Ankle and Foot: Sports
Imaging Series.
AB - The ankle and foot are commonly injured during sporting activities. Clinical
diagnosis can at times be challenging, due to the complex anatomy and multiple
sites of potential injury. In the athlete, there is a reduced threshold for
imaging to clarify diagnosis, guide prognosis, and treatment. Diagnostic imaging
is also helpful in evaluating ongoing symptoms in the subacute or chronic
setting. (c) RSNA, 2017.
PMID- 28514215
TI - Risk Factors for Aneurysm Recurrence.
PMID- 28514217
TI - In Memoriam.
PMID- 28514218
TI - The Effect of Iodine-based Contrast Material on Radiation Dose at CT: It's
Complicated.
PMID- 28514219
TI - Science to Practice: Killing Dormant Cells-Is Targeting Autophagy the Key to
Complete Tumor Response in Transarterial Chemoembolization?
AB - In this issue of Radiology, Gade et al ( 1 ) describe a unique mechanism of
hepatocellular carcinoma (HCC) cells for surviving ischemia induced by
transarterial embolization (TAE)/transarterial chemoembolization (TACE) in a
state of cell cycle arrest-a function that may serve as a defensive shield
against conventional chemotherapeutic agents. This finding adds to our knowledge
and establishes a previously poorly understood mechanism of chemoresistance in
HCC. As the Achilles heel in terms of this process, a concurrent upregulation of
autophagic flux as an adaptive response to TAE-like ischemia was found by the
authors. This is a targetable mechanism that can potentially be exploited for
combined therapeutic approaches of embolotherapy and autophagy inhibition in HCC.
PMID- 28514220
TI - Case 242: Radiation-induced Angiosarcoma.
AB - History In 2004, this woman received a diagnosis of invasive mammillary
carcinoma, tubular variant, strongly positive for estrogen and progesterone
receptors. Her lesion was found at screening mammography performed at an outside
institution when she was 59 years old. She underwent partial mastectomy, with
partial axillary node dissection and sentinel node mapping. A 0.6 * 0.5 cm
Nottingham grade 1 infiltrating ductal carcinoma was removed from the right upper
outer quadrant, margins were free of tumor, and there was no angiolymphatic
invasion. The six dissected lymph nodes were negative for malignancy. Her
surgical history was otherwise unremarkable. Her medical history was positive for
hypercholesterolemia and depression. Pertinent family history included breast
cancer in both her mother and her sister. Given the patient's age, tumor size,
lack of nodal involvement, and clear surgical margins, she met recommended
MammoSite criteria, and she underwent accelerated partial breast radiation. She
subsequently received 340 cGy of radiation twice a day for a total dose of 3400
cGy in 10 administrations in February 2005. Accelerated partial breast radiation
treatment was completed in February 2005, and she received subsequent routine
care. Prior to 2014, the only postoperative complication was a chronic radiation
bed seroma, which required periodic percutaneous drainage. She did not develop
postsurgical lymphedema. In December 2013, 9 years after accelerated partial
breast radiation treatment, she experienced progressive painful pruritic breast
fullness, skin dimpling, and skin discoloration of the mastectomy scar and
radiation bed. She sought medical care in January 2014 after she noticed a
periareolar ulcerating skin plaque, more noticeable nipple retraction, and new
onset of retroareolar aching. At physical examination ( Fig 1 ), there was
generalized periareolar erythema, dimpling, firmness, and fixation involving the
central breast and right upper outer quadrant. There was more conspicuous
retraction of the nipple when compared with that seen at prior examinations.
Nipple discharge was not present. There was a 1-cm periareolar ulcerating skin
plaque. The only discrete palpable finding was lumpectomy bed seroma. There was
no palpable axillary adenopathy. [Figure: see text] A diagnostic mammogram was
obtained and compared with the most recent studies available. Ultrasonography
(US) and magnetic resonance (MR) imaging were performed. Her most recent
mammogram, obtained 3 months earlier in September 2013, reported Breast Imaging
Reporting and Data System (BI-RADS) category 2 findings (ie, stable postoperative
benign findings).
PMID- 28514221
TI - Tracking Eye Movements during CT Interpretation: Inferences of Reader Performance
and Clinical Competency Require Clinically Realistic Procedures for Unconstrained
Search.
PMID- 28514222
TI - Optimum Management of Pulmonary Nodules.
PMID- 28514223
TI - Hematogenous Osteomyelitis in Infants and Children: Imaging of a Changing
Disease.
AB - In children, hematogenous osteomyelitis is an infection that primarily affects
the most vascularized regions of the growing skeleton. The disease has increased
in frequency, virulence, and degree of soft-tissue involvement. The change in
clinical manifestations and management over the past 2 decades should be
reflected in the current imaging approach to the disease. Imaging of infection
must depict the location of a single focus or of multiple foci of involvement and
the presence of drainable collections. This review provides an overview of the
imaging implications directed by the changing epidemiology, the newer insights of
anatomy and pathophysiology, the imaging characteristics with emphasis on
specific locations and disease complications, and the differential diagnosis
considerations. In addition, basic imaging guidelines for appropriate extent of
area to image based on patient age are provided. (c) RSNA, 2017.
PMID- 28514224
TI - Case 246.
PMID- 28514225
TI - Vector and Serologic Survey for Crimean-Congo Hemorrhagic Fever Virus in Poland.
AB - In contrast to animals, Crimean-Congo hemorrhagic fever (CCHF) causes a severe
disease in humans with a high mortality rate. The etiological agent, CCHF virus
(CCHFV), can be transmitted by argasid and ixodid ticks, but arachnids of the
genus Hyalomma, followed by Rhipicephalus and Dermacentor serve as the major
vectors of this virus. The goal of the study was to assess the epidemiological
situation of CCHFV infection in cattle in south-east Poland, and survey for
potential tick vector species. A total of 592 bovine blood samples from animals
located in the southernmost region in Poland were tested by IgG sandwich enzyme
linked immunosorbent assay. Ticks (n = 993) from south-east Poland were collected
from dogs, cats, cattle, and horses and tested by RT-PCR. All 592 serum samples
were negative for IgG antibodies to CCHFV. Of the ticks collected, 125 were
Dermacentor reticulatus and 868 represented Ixodes ricinus, both species are
regarded as potential vectors of CCHFV. All tick samples were negative for the
presence of CCHFV. Considering the zoonotic nature, public health importance, and
the virus increasing spread, it was prudent to assess the seroprevalence of CCHFV
in the south-east area of Poland, bordering with CCHFV endemic areas. It seems
unlikely that CCHFV infection will suddenly spread in Poland, but considering the
multiple possibilities of the virus introduction, serosurveys and vector
biosurveillance should be conducted at regular intervals.
PMID- 28514226
TI - The March of Science - The True Story.
PMID- 28514227
TI - Real-Time Evolution of Zika Virus Disease Outbreak, Roatan, Honduras.
AB - A Zika virus disease outbreak occurred in Roatan, Honduras, during September 2015
July 2016. Blood samples and clinical information were obtained from 183 patients
given a clinical diagnosis of suspected dengue virus infection. A total of 79
patients were positive for Zika virus, 13 for chikungunya virus, and 6 for dengue
virus.
PMID- 28514228
TI - Outcomes for 2 Children after Peripartum Acquisition of Zika Virus Infection,
French Polynesia, 2013-2014.
AB - Congenital Zika virus infection is associated with severe brain anomalies and
impaired function. To determine outcomes, we followed 2 affected children for ~30
months. For 1 who was symptomatic at birth, transient hepatitis developed.
However, neurodevelopment for both children was age appropriate.
PMID- 28514229
TI - An open source, wireless capable miniature microscope system.
AB - OBJECTIVE: Fluorescence imaging through head-mounted microscopes in freely
behaving animals is becoming a standard method to study neural circuit function.
Flexible, open-source designs are needed to spur evolution of the method.
APPROACH: We describe a miniature microscope for single-photon fluorescence
imaging in freely behaving animals. The device is made from 3D printed parts and
off-the-shelf components. These microscopes weigh less than 1.8 g, can be
configured to image a variety of fluorophores, and can be used wirelessly or in
conjunction with active commutators. Microscope control software, based in Swift
for macOS, provides low-latency image processing capabilities for closed-loop, or
BMI, experiments. MAIN RESULTS: Miniature microscopes were deployed in the
songbird premotor region HVC (used as a proper name), in singing zebra finches.
Individual neurons yield temporally precise patterns of calcium activity that are
consistent over repeated renditions of song. Several cells were tracked over
timescales of weeks and months, providing an opportunity to study learning
related changes in HVC. SIGNIFICANCE: 3D printed miniature microscopes, composed
completely of consumer grade components, are a cost-effective, modular option for
head-mounting imaging. These easily constructed and customizable tools provide
access to cell-type specific neural ensembles over timescales of weeks.
PMID- 28514230
TI - Causes of Death of Residents in ACGME-Accredited Programs 2000 Through 2014:
Implications for the Learning Environment.
AB - PURPOSE: To systematically study the number of U.S. resident deaths from all
causes, including suicide. METHOD: The more than 9,900 programs accredited by the
Accreditation Council for Graduate Medical Education (ACGME) annually report the
status of residents. The authors aggregated ACGME data on 381,614 residents in
training during years 2000 through 2014. Names of residents reported as deceased
were submitted to the National Death Index to learn causes of death. Person-year
calculations were used to establish resident death rates and compare them with
those in the general population. RESULTS: Between 2000 and 2014, 324 individuals
(220 men, 104 women) died while in residency. The leading cause of death was
neoplastic disease, followed by suicide, accidents, and other diseases. For male
residents the leading cause was suicide, and for female residents, malignancies.
Resident death rates were lower than in the age- and gender-matched general
population. Temporal patterns showed higher rates of death early in residency.
Deaths by suicide were higher early in training, and during the first and third
quarters of the academic year. There was no upward or downward trend in resident
deaths over the 15 years of this study. CONCLUSIONS: Neoplastic disease and
suicide were the leading causes of death in residents. Data for death by suicide
suggest added risk early in residency and during certain months of the academic
year. Providing trainees with a supportive environment and with medical and
mental health services is integral to reducing preventable deaths and fostering a
healthy physician workforce.
PMID- 28514231
TI - Preoperative Pain Neuroscience Education Combined With Knee Joint Mobilization
for Knee Osteoarthritis: A Randomized Controlled Trial.
AB - OBJECTIVES: This study aimed to first compare the effects of a preoperative
treatment combining pain neuroscience education (PNE) with knee joint
mobilization versus biomedical education with knee joint mobilization on central
sensitization (CS) in patients with knee osteoarthritis, both before and after
surgery. Second, we wanted to compare the effects of both interventions on knee
pain, disability, and psychosocial variables. MATERIALS AND METHODS: Forty-four
patients with knee osteoarthritis were allocated to receive 4 sessions of either
PNE combined with knee joint mobilization or biomedical education with knee joint
mobilization before surgery. All participants completed self-administered
questionnaires and quantitative sensory testing was performed at baseline, after
treatment and at a 1 month follow-up (all before surgery), and at 3 months after
surgery. RESULTS: Significant and clinically relevant differences before and
after surgery were found after treatments for both knee pain and disability, and
some measures of CS (ie, widespread hyperalgesia, CS inventory), with no
significant between-group differences. Other indicators of CS (ie, conditioned
pain modulation, temporal summation) did not change over time following either
treatment, and in some occasions the observed changes were not in the expected
direction. Patients receiving PNE with knee joint mobilization achieved greater
improvements in psychosocial variables (pain catastrophizing, kinesiophobia) both
before and after surgery. DISCUSSION: Preoperative PNE combined with knee joint
mobilization did not produce any additional benefits over time for knee pain and
disability, and CS measures compared with biomedical education with knee joint
mobilization. Superior effects in the PNE with knee joint mobilization group were
only observed for psychosocial variables related to pain catastrophizing and
kinesiophobia.
PMID- 28514233
TI - Energy Balance over One Athletic Season.
AB - INTRODUCTION: Magnitude and variation in energy balance (EB) components over an
athletic season are largely unknown. PURPOSE: We investigated the longitudinal
changes in EB over one season and explored the association between EB variation
and change in the main fat-free mass (FFM) components in highly trained athletes.
METHODS: Eighty athletes (54 males; handball, volleyball, basketball, triathlete,
and swimming) were evaluated from the beginning of the season to the main
competition stage. Resting and total energy expenditure (REE and TEE,
respectively) were assessed by indirect calorimetry and doubly labeled water,
respectively. Physical activity energy expenditure was calculated as TEE - 0.1
TEE - REE. Fat mass (FM), FFM, and bone mineral were evaluated with dual-energy x
ray absorptiometry; changed body energy stores were calculated as
1.0(DeltaFFM/Deltatime) + 9.5(DeltaFM/Deltatime). Total-body water (TBW) and its
compartments were assessed through dilution techniques, and total-body protein
was calculated from a four-compartment model, with body volume assessed by air
displacement plethysmography. RESULTS: Although a negative EB of -17.4 +/- 72.7
kcal.d was observed (P < 0.05), EB varied widely among sports and across sex
groups resulting in a net weight increase (0.7 +/- 2.3 kg) that is attributable
to significant changes in FFM (1.2 +/- 1.6 kg) and FM (-0.7 +/- 1.5 kg) (P <
0.05). EB was related with TBW and intracellular water (r = 0.354, r = 0.257, P <
0.05, respectively), regardless of sex, sports, and age. CONCLUSIONS: The mean
negative EB observed over the season resulted from the rate of FM use and FFM
accretion, but with a large variation by sex and sports. TBW, but not total-body
protein or mineral balance, explained the magnitude of EB, which means that
athletes under a positive or a negative EB showed a TBW expansion or shrinkage,
respectively, specifically within the cells, over one athletic season.
PMID- 28514232
TI - PPARgamma Agonists Attenuate Trigeminal Neuropathic Pain.
AB - OBJECTIVES: The aim of this study is to investigate the role of peroxisome
proliferator-activated receptor-gamma isoform (PPARgamma), in trigeminal
neuropathic pain utilizing a novel mouse trigeminal inflammatory compression
(TIC) injury model. RESULTS: The study determined that the PPARgamma nuclear
receptor plays a significant role in trigeminal nociception transmission,
evidenced by: 1) Intense PPARgamma immunoreactivity is expressed 3 weeks after
TIC nerve injury in the spinal trigeminal caudalis, the termination site of
trigeminal nociceptive nerve fibers. 2) Systemic administration of a PPARgamma
agonist, pioglitazone (PIO), attenuates whisker pad mechanical allodynia at doses
of 300 mg/kg i.p. and 600 mg/kg p.o. 3) Administration of a PPARgamma antagonist,
GW9662 (30 mg/kg i.p.), prior to providing the optimal dose of PIO (300 mg/kg
i.p.) blocked the analgesic effect of PIO. DISCUSSION: This is the first study
localizing PPARgamma immunoreactivity throughout the brainstem trigeminal sensory
spinal nucleus (spV) and its increase three weeks after TIC nerve injury. This is
also the first study to demonstrate that activation of PPARgamma attenuates
trigeminal hypersensitivity in the mouse TIC nerve injury model. The findings
presented here suggest the possibility of utilizing the FDA approved diabetic
treatment drug, PIO, as a new therapeutic that targets PPARgamma for treatment of
patients suffering from orofacial neuropathic pain.
PMID- 28514234
TI - Associations Between Physical Pain, Pain Management, and Frequency of Nonmedical
Prescription Opioid Use Among Young Adults: A Sex-specific Analysis.
AB - OBJECTIVES: We sought to determine sex-specific associations between experiences
of physical pain, pain management, and frequency of nonmedical prescription
opioid (NMPO) use among young adults. METHODS: Among participants enrolled in the
Rhode Island Young Adult Prescription Drug Study, we identified associations
between physical pain in the past 6 months, pain history, pain management,
polysubstance use, and weekly NMPO use. In sex-specific models, independent
correlates of weekly NMPO use were identified via modified stepwise Poisson
regression. RESULTS: Of 199 participants, the mean age was 24.6, and 65.3% were
male. The racial composition was 16.6% black, 60.8% white, and 22.1% mixed or
other race. A total of 119 (59.8%) participants reported weekly or greater NMPO
use. The majority of male (86.2%) and female (84.1%) participants reported ever
experiencing severe pain. A majority of males (72.3%) and females (81.2%)
reported that they engaged in NMPO use to treat their physical pain, and one
quarter (26.9%) of males and one-third (36.2%) of females had been denied a
prescription from a doctor to treat severe pain. Among males, frequent NMPO use
was independently associated with white race (P < 0.001) and reporting greater
physical pain (P = 0.002). Among females, older age (P = 0.002) and monthly or
greater nonmedical benzodiazepine use (P = 0.001) were independently associated
with weekly NMPO use. CONCLUSIONS: Among young men in Rhode Island, physical pain
may be related to frequent NMPO use. More research is needed to identify sex
specific, pain-related factors that are linked with NMPO use to improve harm
reduction and pain management interventions.
PMID- 28514236
TI - A Kinked Epidural Needle Tip Preventing Placement of an Epidural Catheter.
PMID- 28514235
TI - Ondansetron Does Not Reduce Withdrawal in Patients With Physical Dependence on
Chronic Opioid Therapy.
AB - OBJECTIVES: Individuals taking opioids for an extended period of time may become
physically dependent, and will therefore experience opioid withdrawal should they
stop taking the medication. Previous work in animal and human models has shown
that the serotonin (5-HT3) receptor may be implicated in opioid withdrawal. In
this study, we investigated if ondansetron, a 5-HT3-receptor antagonist, could
reduce the symptoms of opioid withdrawal after chronic opioid exposure in humans.
METHODS: In this double-blinded, randomized, crossover study, 33 chronic back
pain patients (N = 33) were titrated onto sustained-release oral morphine for 30
days. After titration, participants attended 2 study sessions, 1 week apart, in
which opioid withdrawal was induced with intravenous naloxone, with or without 8
mg intravenous ondansetron pretreatment. Opioid withdrawal symptoms were assessed
by a blinded research assistant (objective opioid withdrawal score [OOWS]) and by
the research participant (subjective opioid withdrawal score [SOWS]). RESULTS:
Clinically significant signs of withdrawal were observed during both the
ondansetron (DeltaOOWS = 3.58 +/- 2.22, P < 0.0001; DeltaSOWS = 12.48 +/- 11.18,
P < 0.0001) and placebo sessions (DeltaOOWS = 3.55 +/- 2.39, P < 0.0001;
DeltaSOWS = 12.21 +/- 10.72, P < 0.0001), but no significant differences were
seen between the treatment sessions in either the OOWS or SOWS scores.
CONCLUSION: We hypothesized that ondansetron would reduce opioid withdrawal
symptoms in human subjects, but found no difference in withdrawal severity
between ondansetron and placebo sessions. These findings suggest that more
investigation may be necessary to determine if 5-HT3-receptor antagonists are
suitable treatment options for opioid withdrawal.
PMID- 28514237
TI - Oral Ketamine in Treatment-Resistant Depression: A Clinical Effectiveness Case
Series.
AB - PURPOSE: The aim of the study was to assess the effectiveness, tolerability, and
safety of oral ketamine as an antidepressant treatment in adults with treatment
resistant depression. METHODS: We reviewed retrospective data on 22 patients with
treatment-resistant depression, who failed at least 3 adequate antidepressant
treatment trials and 1 adequate trial of repetitive transcranial magnetic
stimulation; subsequently, they received open-label treatment with oral ketamine,
commenced at a dose of 50 mg every 3 days, titrated up by 25 mg every 3 days,
according to response and tolerability. The primary outcome measure was the Beck
Depression Inventory II, which was used to rate subjective mood improvement at
baseline and then at each follow-up visit. Data about adverse effects related to
ketamine and a self-harm risk assessment were also obtained. FINDINGS: Over the
course of treatment, 18% of the patients showed greater than 50% reduction in the
Beck Depression Inventory II scores, 14% reported partial improvement in mood
symptoms, while 45% had no response to ketamine and 23% showed a mild worsening
in their depressive symptoms. The most frequent adverse effects were acute
dissociation, dizziness, blurred vision, numbness and sedation. Neither serious
adverse effects, nor any cases of abuse or dependence were observed. CONCLUSIONS:
Although this case series found oral ketamine to be safe and well tolerated, the
findings also showed rather modest effectiveness of oral ketamine in treatment
resistant depression, with only approximately 30% reporting some benefit and
approximately 70% reporting no change or worsening of mood. However, bearing in
mind the limitations of this small, open-label case series, further exploration
of the effectiveness of oral ketamine is warranted.
PMID- 28514238
TI - The Influence of Maternal Pragmatics on the Language Skills of Children with
Autism.
AB - OBJECTIVE: This study examined the relationship between mothers' pragmatics and
child language in autism spectrum disorder (ASD) and non-ASD language delay (LD)
mother-child dyads. METHODS: Participants consisted of 20 dyads of mothers and
their toddlers aged 24 to 48 months, with ASD (n = 10) or non-ASD LD (n = 10).
Groups were matched on child chronological age, language, and cognition. Maternal
pragmatic language was qualified based on the degree of pragmatic violations
during a semistructured interview, and was examined in relation to both child
language, as measured by the Preschool Language Scale-4 and maternal use of
language facilitation strategies during play. RESULTS: Lower rates of maternal
pragmatic violations were associated with higher expressive language scores in
children with ASD, and with higher receptive language scores for children with
non-ASD LD. Within ASD dyads, maternal pragmatic violations were negatively
related to mothers' use of linguistic expansions. CONCLUSION: These findings
indicate that parental pragmatics likely contribute to early language learning,
and that the effects of maternal pragmatics on early language in ASD may be
indirect (e.g., through parents' use of facilitative strategies). Parent-mediated
language interventions for ASD should therefore consider parent pragmatics,
especially given that pragmatic differences have been identified in unaffected
family members of individuals with ASD.
PMID- 28514239
TI - Understanding Women's Sexual Behaviors That May Put Them at Risk for Human
Papillomavirus-Related Neoplasias: What Should We Ask?
AB - OBJECTIVES: Human papillomavirus is a multifocal infection that can involve the
cervix, vagina, vulva, anus, and oropharynx. Our study aimed to determine whether
standard sexual history questions regarding anal intercourse identify women
participating in anal-related sexual practices. MATERIALS AND METHODS: A cross
sectional survey was conducted at the dysplasia clinic of a large academic
medical center. Women presenting with human papillomavirus-related cervical,
vulvar, or vaginal abnormalities were eligible. Participants completed a self
administered sexual history questionnaire that included standard sexual history
questions and more detailed questions about sexual practices. Additional
demographic information was obtained from chart review. RESULTS: A total of 149
eligible women were approached, 125 (84%) consented and enrolled (ages = 21-65
years). Forty-seven (44%) reported participating in some type of anal-related
sexual practice: anal fingering, oral-anal penetration, or anal intercourse. Of
those participating in anal-related practices, 5 (11%) reported only anal
fingering or oral-anal penetration. Thus, adding the new anal questions detected
an additional 5% of women with high-risk anal behaviors that may have been missed
by the standard question (p = .06). Seventy-nine women (63%) reported receiving
oral penetration of the vagina, and 102 (82%) reported receiving vaginal
fingering. Fifty-nine women (47%) used sex toys: 58 (98%) used sex toys
vaginally, with 5 (8.5%) using them also anally. CONCLUSIONS: Women are willing
to report their participation in a range of sexual practices. Of those who
participated in anal practices, 11% did not have anal intercourse. Adding
additional sexual health questions to clinical intake forms may enable clinicians
to better counsel their patients on risky sexual behaviors.
PMID- 28514240
TI - Raising the Alarm on Brain Attacks in Surgical Patients: Are We Doing Enough to
Prevent and Treat Postoperative Strokes?
PMID- 28514241
TI - Phrenic Nerve Palsy and Regional Anesthesia for Shoulder Surgery: Anatomical,
Physiologic, and Clinical Considerations.
AB - Regional anesthesia has an established role in providing perioperative analgesia
for shoulder surgery. However, phrenic nerve palsy is a significant complication
that potentially limits the use of regional anesthesia, particularly in high-risk
patients. The authors describe the anatomical, physiologic, and clinical
principles relevant to phrenic nerve palsy in this context. They also present a
comprehensive review of the strategies for reducing phrenic nerve palsy and its
clinical impact while ensuring adequate analgesia for shoulder surgery. The most
important of these include limiting local anesthetic dose and injection volume
and performing the injection further away from the C5-C6 nerve roots. Targeting
peripheral nerves supplying the shoulder, such as the suprascapular and axillary
nerves, may be an effective alternative to brachial plexus blockade in selected
patients. The optimal regional anesthetic approach in shoulder surgery should be
tailored to individual patients based on comorbidities, type of surgery, and the
principles described in this article.
PMID- 28514242
TI - Risks of Cardiovascular Adverse Events and Death in Patients with Previous Stroke
Undergoing Emergency Noncardiac, Nonintracranial Surgery: The Importance of
Operative Timing.
AB - BACKGROUND: The outcomes of emergent noncardiac, nonintracranial surgery in
patients with previous stroke remain unknown. METHODS: All emergency surgeries
performed in Denmark (2005 to 2011) were analyzed according to time elapsed
between previous ischemic stroke and surgery. The risks of 30-day mortality and
major adverse cardiovascular events were estimated as odds ratios (ORs) and 95%
CIs using adjusted logistic regression models in a priori defined groups
(reference was no previous stroke). In patients undergoing surgery immediately
(within 1 to 3 days) or early after stroke (within 4 to 14 days), propensity
score matching was performed. RESULTS: Of 146,694 nonvascular surgeries
(composing 98% of all emergency surgeries), 5.3% had previous stroke (mean age,
75 yr [SD = 13]; 53% women, 50% major orthopedic surgery). Antithrombotic
treatment and atrial fibrillation were more frequent and general anesthesia less
frequent in patients with previous stroke (all P < 0.001). Risks of major adverse
cardiovascular events and mortality were high for patients with stroke less than
3 months (20.7 and 16.4% events; OR = 4.71 [95% CI, 4.18 to 5.32] and 1.65 [95%
CI, 1.45 to 1.88]), and remained increased for stroke within 3 to 9 months (10.3
and 12.3%; OR = 1.93 [95% CI, 1.55 to 2.40] and 1.20 [95% CI, 0.98 to 1.47]) and
stroke more than 9 months (8.8 and 11.7%; OR = 1.62 [95% CI, 1.43 to 1.84] and
1.20 [95% CI, 1.08 to 1.34]) compared with no previous stroke (2.3 and 4.8%
events). Major adverse cardiovascular events were significantly lower in 323
patients undergoing immediate surgery (21%) compared with 323 successfully
propensity-matched early surgery patients (29%; P = 0.029). CONCLUSIONS: Adverse
cardiovascular outcomes and mortality were greatly increased among patients with
recent stroke. However, events were higher 4 to 14 days after stroke compared
with 1 to 3 days after stroke.
PMID- 28514243
TI - Celiac Disease Symptom Resolution: Effectiveness of the Gluten-free Diet.
AB - OBJECTIVE: The aim of the study was to evaluate the efficacy of the gluten-free
diet (GFD) on gastrointestinal (GI) and extra-intestinal (EI) symptom resolution
and identify predictors for persistence of symptoms in all celiac patients at the
University of Chicago. METHODS: We conducted a retrospective chart review from
2002 to 2015. GI symptoms included abdominal pain, bloating, constipation,
diarrhea, failure to thrive/weight loss, nausea, reflux, and vomiting. EI
symptoms included abnormal liver enzymes, arthralgia/arthritis, dermatitis
herpetiformis, alopecia, fatigue, headache, anemia, stomatitis, myalgia,
psychiatric disorders, rashes, seizures, neuropathy, short stature, delayed
puberty, osteoporosis, and infertility. RESULTS: A total of 554 patients (227
children) with celiac disease (CeD) were included. Abdominal pain, diarrhea and
failure to thrive were the most common GI symptoms in children whereas diarrhea,
bloating, and abdominal pain were most common in adults. Short stature, fatigue,
and headache were the most common EI symptoms in children whereas iron deficiency
anemia, fatigue, and headache/psychiatric disorders were most common in adults.
Children had significantly higher rates of EI and GI symptom resolution as
compared to adults, with greater rates of improvements in GI versus EI symptoms
at more than 24 months. Long duration of symptoms, female sex, and non-adherence
to a GFD were the most important significant predictors of failure to clinically
improve. CONCLUSIONS: On a strict GFD, children report greater rates of both GI
and EI symptom resolution as compared to adults with greater rates of improvement
in GI over EI symptoms. Early recognition of CeD and close attention to diet
adherence may help in symptom resolution.
PMID- 28514245
TI - Comparison of Ocular Lubricant Osmolalities.
AB - PURPOSE: The aim of this study was to evaluate the osmolality of commercially
available ocular tear lubricants. METHODS: Thirty-seven (n = 37) ocular
lubricants, measured three times each, were evaluated for osmolality using a
vapor pressure osmometer (Wescor VAPRO 5520). The osmometer was calibrated before
each use, and the order of the lubricants was randomized. Ambient temperature and
humidity were monitored for stability. RESULTS: Of the 37 ocular lubricants
tested, 35 (94.6%) had an osmolality of less than 295 mmol/kg, one (2.7%) had
between 295 and 308 mmol/kg, and one (2.7%) had more than 308 mmol/kg. The
ambient room temperature was stable and ranged from 21.9 degrees C to 22.0
degrees C, and the relative humidity ranged from 21.2% to 25.6% during
experimentation. When ocular lubricants were grouped by ingredient
(carboxymethylcellulose and hydroxylpropyl methylcellulose, hyaluronic acid, and
hydroxypropyl guar), no significant difference in osmolality was noted between
groups (Mann-Whitney U test, P > .05). CONCLUSIONS: The majority of the ocular
lubricants tested had low osmolalities, mimicking the osmolarity of newly formed
tears (295 to 300 mOsm/L). Several factors need to be considered when choosing a
tear lubricant, which have more complex formulations than ever. Knowledge of
their osmolality may be an added parameter to consider when choosing therapeutic
options for dry eye.
PMID- 28514244
TI - The Safety of Soft Contact Lenses in Children.
AB - PURPOSE: There is increasing interest in fitting children with soft contact
lenses. This review collates data from a range of studies to estimate the
incidence of complications, specifically corneal infiltrative events and
microbial keratitis, in patients under the age of 18 years. METHODS: Peer-review
papers were identified using PubMed and the Web of Science. A broad range of
studies are summarized including large-scale epidemiological studies of contact
lens-related complications, hospital-based case series, long- and short-term
prospective studies, and multicenter retrospective studies. RESULTS: Nine
prospective studies representing 1800 patient years of wear in 7- to 19-year-olds
include safety outcomes. In three large prospective studies representing between
159 and 723 patient years of soft contact lens wear in patients 8 to 14 years,
the incidence of corneal infiltrative events is up to 136 per 10,000 years. Data
from a large retrospective study show similar rates of corneal infiltrative
events: 97 per 10,000 years in 8- to 12-year-olds (based on 411 patient years of
wear) and 335 per 10,000 years in 13- to 17-year-olds (based on 1372 patient
years of wear). None of the prospective studies report any cases of microbial
keratitis. Five clinical studies where safety data are not reported constitute a
further 493 patient years. One retrospective study found no cases of microbial
keratitis occurred in 8- to 12-year-olds (411 patient years) and an incidence of
15 per 10,000 patient years in 13- to 17-year-olds (1372 patient years)-no higher
than the incidence of microbial keratitis in adults wearing soft contact lenses
on an overnight basis. CONCLUSIONS: The overall picture is that the incidence of
corneal infiltrative events in children is no higher than in adults, and in the
youngest age range of 8 to 11 years, it may be markedly lower.
PMID- 28514246
TI - The Development of the Chinese Intermittent Exotropia Questionnaire.
AB - PURPOSE: The Intermittent Exotropia Questionnaire (IXTQ) is a child, proxy, and
parent report of health-related quality of life specific to children with
intermittent exotropia (IXT). The present study aimed to develop a Chinese
language version of the IXTQ (CIXTQ) and evaluate its validity and reliability
when used in Chinese IXT children and their parents. METHODS: The IXTQ was
translated into Chinese. One hundred seventy-five IXT children (2 to 17 years
old) and 151 orthotropic control children (2 to 17 years old) along with one of
their parents were recruited. Children 5 to 17 years old completed the 5- to 7
year-old or the 8- to 17-year-old child questionnaire of the CIXTQ according to
their age. Parents of all children (2 to 17 years old) completed the proxy and
parent questionnaires of the CIXTQ. Psychometric properties of the CIXTQ were
examined for floor and ceiling effects, construct validity, item-internal
consistency, discriminative validity, Cronbach alpha coefficient and test-retest
reliability. RESULTS: No items were found to have strong floor or ceiling
effects. Principal component analysis identified that the CIXTQ had a similar
structure to the original English version. The median scores of each
questionnaire in the CIXTQ among children with IXT and their parents were
significantly lower than those among control subjects (P < .001). Cronbach alpha
coefficients ranged from 0.869 to 0.931, and test-retest reliabilities ranged
from 0.898 to 0.981, for each questionnaire in the CIXTQ. CONCLUSIONS: The CIXTQ
is a useful tool to evaluate the influence of IXT on health-related quality of
life among Chinese IXT children and their parents.
PMID- 28514247
TI - Corneal Equilibrium Flux as a Function of Corneal Surface Oxygen Tension.
AB - PURPOSE: Oxygen is essential for aerobic mammalian cell physiology. Oxygen
tension (PO2) should reach a minimum at some position within the corneal stroma,
and oxygen flux should be zero, by definition, at this point as well. We found
the locations and magnitudes of this "corneal equilibrium flux" (xmin) and
explored its physiological implications. METHODS: We used an application of the
Monod kinetic model to calculate xmin for normal human cornea as anterior surface
PO2 changes from 155 to 20 mmHg. RESULTS: We find that xmin deepens, broadens,
and advances from 1.25 MUm above the endothelial-aqueous humor surface toward the
epithelium (reaching a position 320 MUm above the endothelial-aqueous humor
surface) as anterior corneal surface PO2 decreases from 155 to 20 mmHg.
CONCLUSIONS: Our model supports an anterior corneal oxygen flux of 9 MUL O2 . cm
. h and an epithelial oxygen consumption of approximately 4 MUL O2 . cm . h. Only
at the highest anterior corneal PO2 does our model predict that oxygen diffuses
all the way through the cornea to perhaps reach the anterior chamber. Of most
interest, corneal oxygen consumption should be supported down to a corneal
surface PO2 of 60 to 80 mmHg but declines below this range. We conclude that the
critical oxygen tension for hypoxia induced corneal swelling is more likely this
range rather than a fixed value.
PMID- 28514248
TI - Foveal Curvature and Asymmetry Assessed Using Optical Coherence Tomography.
AB - PURPOSE: The aims of this study were to use cross-sectional optical coherence
tomography imaging and custom curve fitting software to evaluate and model the
foveal curvature as a spherical surface and to compare the radius of curvature in
the horizontal and vertical meridians and test the sensitivity of this technique
to anticipated meridional differences. METHODS: Six 30-degree foveal-centered
radial optical coherence tomography cross-section scans were acquired in the
right eye of 20 clinically normal subjects. Cross sections were manually
segmented, and custom curve fitting software was used to determine foveal pit
radius of curvature using the central 500, 1000, and 1500 MUm of the foveal
contour. Radius of curvature was compared across different fitting distances.
Root mean square error was used to determine goodness of fit. The radius of
curvature was compared between the horizontal and vertical meridians for each
fitting distance. RESULTS: There radius of curvature was significantly different
when comparing each of the three fitting distances (P < .01 for each comparison).
The average radii of curvature were 970 MUm (95% confidence interval [CI], 913 to
1028 MUm), 1386 MUm (95% CI, 1339 to 1439 MUm), and 2121 MUm (95% CI, 2066 to
2183) for the 500-, 1000-, and 1500-MUm fitting distances, respectively. Root
mean square error was also significantly different when comparing each fitting
distance (P < .01 for each comparison). The average root mean square errors were
2.48 MUm (95% CI, 2.41 to 2.53 MUm), 6.22 MUm (95% CI, 5.77 to 6.60 MUm), and
13.82 MUm (95% CI, 12.93 to 14.58 MUm) for the 500-, 1000-, and 1500-MUm fitting
distances, respectively. The radius of curvature between the horizontal and
vertical meridian radii was statistically different only in the 1000- and 1500
MUm fitting distances (P < .01 for each), with the horizontal meridian being
flatter than the vertical. CONCLUSIONS: The foveal contour can be modeled as a
sphere with low curve fitting error over a limited distance and capable of
detecting subtle foveal contour differences between meridians.
PMID- 28514249
TI - Heart Transplantation From DCD donors: From the Bedside to the Bench.
PMID- 28514250
TI - Accept or Decline? An Analytics-Based Decision Tool for Kidney Offer Evaluation.
AB - BACKGROUND: When a deceased-donor kidney is offered to a waitlisted candidate,
the decision to accept or decline the organ relies primarily upon a
practitioner's experience and intuition. Such decisions must achieve a delicate
balance between estimating the immediate benefit of transplantation and the
potential for future higher-quality offers. However, the current experience-based
paradigm lacks scientific rigor and is subject to the inaccuracies that plague
anecdotal decision-making. METHODS: A data-driven analytics-based model was
developed to predict whether a patient will receive an offer for a deceased-donor
kidney at Kidney Donor Profile Index thresholds of 0.2, 0.4, and 0.6, and at
timeframes of 3, 6, and 12 months. The model accounted for Organ Procurement
Organization, blood group, wait time, DR antigens, and prior offer history to
provide accurate and personalized predictions. Performance was evaluated on data
sets spanning various lengths of time to understand the adaptability of the
method. RESULTS: Using United Network for Organ Sharing match-run data from March
2007 to June 2013, out-of-sample area under the receiver operating characteristic
curve was approximately 0.87 for all Kidney Donor Profile Index thresholds and
timeframes considered for the 10 most populous Organ Procurement Organizations.
As more data becomes available, area under the receiver operating characteristic
curve values increase and subsequently level off. CONCLUSIONS: The development of
a data-driven analytics-based model may assist transplant practitioners and
candidates during the complex decision of whether to accept or forgo a current
kidney offer in anticipation of a future high-quality offer. The latter holds
promise to facilitate timely transplantation and optimize the efficiency of
allocation.
PMID- 28514252
TI - Mechanisms of distraction in acute pain perception and modulation.
PMID- 28514251
TI - Hepatic Hemodynamics and Portal Flow Modulation: The A2ALL Experience.
AB - OBJECTIVE: A principal aim of the Adult-to-Adult Living Donor Liver
Transplantation Cohort Study was to study hepatic blood flow and effect of portal
flow modulation on graft outcomes in the setting of increasing use of smaller and
left lobe grafts. METHODS: Recipients of 274 living donor liver transplant were
enrolled in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study,
including 233 (85.0%) right lobes, 40 (14.6%) left lobes, and 1 (0.5%) left
lateral section. Hepatic hemodynamics were recorded after reperfusion. A total of
57 portal flow modulations were performed on 52 subjects. RESULTS: Modulation
lowered portal pressure in 68% of subjects with inconsistent effects on hepatic
arterial and portal flow. A higher rate of graft dysfunction was observed in
modulated vs. unmodulated subjects (31% vs. 18%; P = 0.03); however, graft
survival in modulated subjects was not different from unmodulated subjects at 3
years. CONCLUSIONS: These results suggest the need for a study using a
prespecified portal flow modulation protocol with defined indications to better
define the effects of these interventions.
PMID- 28514253
TI - Widespread effects of clinically unilateral focal nerve injuries.
PMID- 28514254
TI - Reply.
PMID- 28514255
TI - A conceptual framework for "updating the definition of pain".
PMID- 28514256
TI - Reply.
PMID- 28514257
TI - The effect of nothing? Time to abandon the concept of placebo.
PMID- 28514258
TI - Reply.
PMID- 28514259
TI - Does Type 1 Diabetes Mellitus Affect the Shear Wave Velocity of the Thyroid Gland
of Children Without Autoimmune Thyroiditis?
AB - OBJECTIVE: The aim of this study is to evaluate the shear wave velocity (SWV) of
the thyroid gland with acoustic radiation force impulse elastography in children
with type 1 diabetes mellitus (T1D). MATERIALS AND METHODS: Between November 2015
and April 2016, 35 T1D patients who were referred to our hospital's endocrinology
outpatient clinic (mean age, 11.88 +/- 4.1 years) and 30 children (mean age, 11.3
+/- 3.08 years) in the control group were enrolled in the study. Five acoustic
radiation force impulse elastography measurements from each lobe of the thyroid
gland in m/s were recorded. Diabetes age, hemoglobin A1c, and C-peptide levels
were recorded in T1D patients. Statistical analyses were performed using SPSS
version 21 (IBM Corporation, Armonk, NY). RESULTS: The mean SWV of the thyroid
gland in T1D patients and the control group was 1.11 +/- 0.21 and 1.29 +/- 0.23
m/s, respectively. The mean SWV of the thyroid gland in T1D patients was lower
than that in the control group and this was significant (P = 0.002). The mean SWV
of the thyroid gland was not correlated with hemoglobin A1c level, body mass
index, or the insulin dose in T1D patients. CONCLUSIONS: The present study showed
that T1D affects the thyroid gland stiffness even in patients without autoimmune
thyroiditis. Acoustic radiation force impulse elastography may be a useful method
in determining early changes in thyroid gland in T1D and may be used as a
screening tool.
PMID- 28514260
TI - Differential Diagnostic Value of Obstructive and Nonobstructive Azoospermia by
Scrotal Ultrasound.
AB - Our objective was to assess the differential diagnostic value of classification
of obstructive versus nonobstructive azoospermia by scrotal ultrasound. Forty
patients with azoospermia were selected for our study (ages, 23-35; average, 29
+/- 5.34 years). Patients were divided into the obstructive (17) or
nonobstructive (23) azoospermia category. Twenty "healthy" volunteers were
selected for the control group. We observed the testis, epididymis, and vas
deferens in all subjects. Testicular volumes were calculated and compared with
the control group for both obstructive and nonobstructive groups. Cystic or
tubular dilation of the epididymis was found in all patients with obstructive
azoospermia. The patients with nonobstructive azoospermia had no significant
abnormalities of the epididymis. There was no difference in the testicular
volumes between the patients with obstructive azoospermia and healthy controls (P
> 0.05). However, the testicular volumes of patients with nonobstructive
azoospermia were smaller than those of healthy volunteers (P < 0.05). It is
helpful to identify obstructive and nonobstructive azoospermia by scrotal
ultrasound, because it is a less invasive method that can be used to isolate
probable treatment options.
PMID- 28514261
TI - Doppler Ultrasound Evaluation of Circulatory Support Devices.
AB - In the setting of mechanical circulatory support devices, including ventricular
assist devices, extracorporeal membrane oxygenation, intraaortic balloon pumps,
and the total artificial heart, the spectral Doppler waveform is significantly
altered, reflecting systemic hemodynamic changes. As the prevalence of these
devices increases, a better understanding of both the devices themselves and
their associated Doppler ultrasound findings is necessary for accurate image
interpretation. This article reviews the clinical indications, pathophysiology,
and sonographic findings of these devices, with emphasis on the variation in
arterial Doppler waveforms that can be seen with normal function, as well as the
major complications.
PMID- 28514262
TI - Infection Control in Pediatric Spinal Deformity Surgery: A Systematic and
Critical Analysis Review.
PMID- 28514263
TI - Ventricular Energetics in Pediatric Left Ventricular Assist Device Patients: A
Retrospective Clinical Study.
AB - The aim of this study is to estimate the trend of right and left energetic
parameters in left ventricular assist device (LVAD) pediatric patients.
Echocardiographic data were retrospectively collected at the baseline, in the
acute phase after and at the monthly follow-ups till the LVAD explantation to
estimate left and right ventricular energetic parameters. A significant
relationship between the left and right ventricular energetic parameter trends
was found along all the study period. Left ventricular end-systolic pressure
volume relationship improved till the follow-up of 2 months and then
progressively decreases. Left arteroventricular coupling decreases after the
LVAD, and right arteroventricular coupling decreases at the short-term follow-up.
Left ventricular external work, potential energy, and pressure-volume area
decrease at the short-term follow-up and then increase progressively. Right
ventricular external work, potential energy, and pressure-volume area increase
after the LVAD implantation. Left (right) cardiac mechanical efficiency is
improved (worsened) by the LVAD. Energetic variables show that the LVAD benefits
could decrease over time. A continuous and patient tailored LVAD setting could
contribute to prolong LVAD benefits. The introduction of energetic parameters
could lead to a more complete evaluation of LVAD patients' outcome which is a
multiparametric process.
PMID- 28514264
TI - Breaks in Sitting Time: Effects on Continuously Monitored Glucose and Blood
Pressure.
AB - PURPOSE: We examined the effects of interrupting prolonged sitting with multiple
2-min walking breaks or one 30-min continuous walking session on glucose control
and ambulatory blood pressure (ABP). METHODS: Ten overweight/obese, physically
inactive participants (five men; 32 +/- 5 yr; BMI, 30.3 +/- 4.6 kg.m)
participated in this randomized four-trial crossover study, with each trial
performed on a separate, simulated workday lasting 9 h: 1) 30 min of continuous
moderate-intensity (30-min MOD) walking at 71% +/- 4% HRmax; 2) 21 * 2 min bouts
of moderate-intensity (2-min MOD) walking at 53% +/- 5% HRmax, each performed
every 20 min (42 min total); 3) 8 * 2 min bouts of vigorous-intensity (2-min VIG)
walking at 79% +/- 4% HRmax, each performed every hour (16 min total); 4) 9 h of
prolonged sitting (SIT). Participants underwent continuous interstitial glucose
monitoring and ABP monitoring during and after the simulated workday spent in the
laboratory, with primary data analysis from 12:30 h to 07:00 h the next morning.
RESULTS: Compared with SIT (5.6 +/- 1.1 mmol.L), mean 18.7-h glucose was lower
during the 2-min MOD (5.2 +/- 1.1 mmol.L) and 2-min VIG (5.4 +/- 0.9 mmol.L)
trials and mean 18.7-h glucose during the 30-min MOD trial (5.1 +/- 0.8 mmol.L)
was lower than all other trials (P < 0.001). Postprandial glucose was
approximately 7% to 13% lower during all trials compared with SIT (P < 0.001),
with 30-min MOD having the greatest effect. Only the 30-min MOD trial was
effective in reducing systolic ABP from 12:30 to 07:00 h (119 +/- 15 mm Hg) when
compared with SIT (122 +/- 16 mm Hg; P < 0.05). CONCLUSIONS: Replacing sitting
with 2-min MOD walking every 20 min or 2 min of vigorous-intensity walking every
hour during a simulated workday reduced 18.7 h and postprandial glucose, but only
30-min MOD walking was effective for reducing both glucose and systolic ABP.
PMID- 28514268
TI - Primary care perspectives in autosomal dominant polycystic kidney disease.
PMID- 28514265
TI - Television Viewing Time and Inflammatory-Related Mortality.
AB - PURPOSE: Television (TV) viewing time is associated with increased risk of all
cause, cardiovascular and cancer mortality. Although TV time is detrimentally
associated with key inflammatory markers, the associations of TV time with other
inflammatory-related mortality (with a predominant inflammatory, oxidative or
infectious component, but not attributable to cancer or cardiovascular causes),
are unknown. METHODS: Among 8933 Australian adults (4593 never-smokers) from the
baseline (1999-2000) Australian Diabetes, Obesity and Lifestyle Study (median
follow-up, 13.6 yr), we examined TV time in relation to noninflammatory and
inflammatory-related mortality (not attributable to cancer or cardiovascular
causes, hereafter "inflammatory-related" mortality). Because smoking has a
significant inflammatory component, we also examined this relationship in never
smokers. RESULTS: Of 896 deaths, 248 were attributable to cardiovascular disease,
346 to cancer, 130 to other inflammatory-related causes (71 for never-smokers),
and 172 to noninflammatory-related causes (87 for never-smokers). After
multivariate adjustment for age, sex, education, household income, smoking
status, alcohol intake, energy intake, diet, and cardiometabolic risk biomarkers
(model 3), every additional hours per day of TV time was associated with
increased risk of inflammatory-related mortality in the overall population
(hazard ratio, 1.12; 95% confidence interval, 1.00-1.25) and in never-smokers
(1.18; 1.00, 1.40). These results were attenuated after additional adjustment for
leisure-time physical activity. After multivariate adjustment (model 3), no
association was observed for noninflammatory mortality in the overall population
(0.95; 0.85, 1.07), but risk tended to decrease for never-smokers (0.85; 0.75,
1.02). CONCLUSIONS: In summary, before adjustment for leisure-time physical
activity, TV time was associated with increased risk of inflammatory-related
mortality. This is consistent with the hypothesis that high TV viewing may be
associated with a chronic inflammatory state.
PMID- 28514269
TI - Ensuring compliance with the HIPAA Security Rule: Think twice when e-mailing
protected health information.
PMID- 28514270
TI - Recognizing type 1 diabetes mellitus in children & adolescents.
PMID- 28514271
TI - Managing herpes zoster in older adults: Prescribing considerations.
PMID- 28514272
TI - Identifying delirium in older adults with pre-existing mental illness.
AB - Acute delirium complicates care and can be easily overlooked in older adults with
preexisting mental illness. Evidence-based measures have demonstrated that early
diagnosis, identification, and correction of modifiable factors can lead to
improved care and less morbidity in these patients.
PMID- 28514273
TI - Bronchopulmonary sequestration: Improving practice by evaluating for a missed
diagnosis.
AB - Bronchopulmonary sequestration (BPS) is a lung mass that does not communicate
with the tracheobronchial tree or the pulmonary arterial vasculature, and thus
does not play a role in oxygenation. This article discusses the etiology of BPS,
as well as its pathophysiology, signs and symptoms, imaging studies used to
diagnose, and treatment options in both pediatric and adult patients.
PMID- 28514275
TI - Acute exacerbation of COPD: Diagnosis and management.
PMID- 28514276
TI - Sexual network drivers of HIV and herpes simplex virus type 2 transmission.
AB - OBJECTIVES: HIV and herpes simplex virus type 2 (HSV-2) infections are sexually
transmitted and propagate in sexual networks. Using mathematical modeling, we
aimed to quantify effects of key network statistics on infection transmission,
and extent to which HSV-2 prevalence can be a proxy of HIV prevalence.
DESIGN/METHODS: An individual-based simulation model was constructed to describe
sex partnering and infection transmission, and was parameterized with
representative natural history, transmission, and sexual behavior data.
Correlations were assessed on model outcomes (HIV/HSV-2 prevalences) and multiple
linear regressions were conducted to estimate adjusted associations and effect
sizes. RESULTS: HIV prevalence was one-third or less of HSV-2 prevalence. HIV and
HSV-2 prevalences were associated with a Spearman's rank correlation coefficient
of 0.64 (95% confidence interval: 0.58-0.69). Collinearities among network
statistics were detected, most notably between concurrency versus mean and
variance of number of partners. Controlling for confounding, unmarried
mean/variance of number of partners (or alternatively concurrency) were the
strongest predictors of HIV prevalence. Meanwhile, unmarried/married
mean/variance of number of partners (or alternatively concurrency), and
clustering coefficient were the strongest predictors of HSV-2 prevalence. HSV-2
prevalence was a strong predictor of HIV prevalence by proxying effects of
network statistics. CONCLUSION: Network statistics produced similar and
differential effects on HIV/HSV-2 transmission, and explained most of the
variation in HIV and HSV-2 prevalences. HIV prevalence reflected primarily mean
and variance of number of partners, but HSV-2 prevalence was affected by a range
of network statistics. HSV-2 prevalence (as a proxy) can forecast a population's
HIV epidemic potential, thereby informing interventions.
PMID- 28514277
TI - A commitment contract to achieve virologic suppression in poorly adherent
patients with HIV/AIDS.
AB - OBJECTIVE: Assess whether a commitment contract informed by behavioral economics
leads to persistent virologic suppression among HIV-positive patients with poor
antiretroviral therapy (ART) adherence. DESIGN: Single-center pilot randomized
clinical trial and a nonrandomized control group. SETTING: Publicly funded HIV
clinic in Atlanta, Georgia, USA. INTERVENTION: The study involved three arms.
First, participants in the provider visit incentive (PVI) arm received $30 after
attending each scheduled provider visit. Second, participants in the incentive
choice arm were given a choice between the above arrangement and a commitment
contract that made the $30 payment conditional on both attending the provider
visit and meeting an ART adherence threshold. Third, the passive control arm
received routine care and no incentives. PARTICIPANTS: A total of 110 HIV
infected adults with a recent plasma HIV-1 viral load more than 200 copies/ml
despite ART. The sample sizes of the three groups were as follows: PVI, n = 21;
incentive choice, n = 19; and passive control, n = 70. MAIN OUTCOME MEASURE:
Virologic suppression (plasma HIV-1 viral load <=200 copies/ml) at the end of the
incentive period and at an unanticipated postincentive study visit approximately
3 months later. RESULTS: The odds of suppression were higher in the incentive
choice arm than in the passive control arm at the postincentive visit (adjusted
odds ratio 3.93, 95% confidence interval 1.19-13.04, P = 0.025). The differences
relative to the passive control arm at the end of the incentive period and
relative to the PVI arm at both points in time were not statistically
significant. CONCLUSION: Commitment contracts can improve ART adherence and
virologic suppression. TRIAL REGISTRATION: ClinicalTrials.gov identifier
NCT01455740.
PMID- 28514282
TI - Recent progress in anti-HIV broadly neutralizing antibody research.
PMID- 28514281
TI - Acute hyperinsulinemia effects on systemic markers of immune activation in HIV.
AB - : The well treated HIV population remains at risk for insulin resistance and
chronic immune activation. We tested the effects of acute hyperinsulinemia on
inflammation in HIV. Twenty HIV-infected and 10 non-HIV-infected individuals well
matched for BMI underwent oral glucose tolerance testing to stimulate insulin
secretion and assess for changes in circulating soluble CD163, soluble CD14, and
monocyte chemoattract protein 1. Soluble CD14 decreased significantly after
stimulation of hyperinsulinemia and no significant changes in soluble CD163 or
monocyte chemoattract protein 1 were demonstrated in HIV-infected and non-HIV
infected groups.
PMID- 28514279
TI - Impact of alemtuzumab on HIV persistence in an HIV-infected individual on
antiretroviral therapy with Sezary syndrome.
AB - OBJECTIVE: To study the effects of alemtuzumab on HIV persistence in an HIV
infected individual on antiretroviral therapy (ART) with Sezary syndrome, a rare
malignancy of CD4 T cells. DESIGN: Case report. METHODS: Blood was collected 30
and 18 months prior to presentation with Sezary syndrome, at the time of
presentation and during alemtuzumab. T-cell subsets in malignant (CD7-CD26-TCR
VBeta2+) and nonmalignant cells were quantified by flow cytometry. HIV-DNA in
total CD4 T cells, in sorted malignant and nonmalignant CD4 T cells, was
quantified by PCR and clonal expansion of HIV-DNA assessed by full-length next
generation sequencing. RESULTS: HIV-hepatitis B virus coinfection was diagnosed
and antiretroviral therapy initiated 4 years prior to presentation with Sezary
syndrome and primary cutaneous anaplastic large cell lymphoma. The patient
received alemtuzumab 10 mg three times per week for 4 weeks but died 6 weeks post
alemtuzumab. HIV-DNA was detected in nonmalignant but not in malignant CD4 T
cells, consistent with expansion of a noninfected CD4 T-cell clone. Full-length
HIV-DNA sequencing demonstrated multiple defective viruses but no identical or
expanded sequences. Alemtuzumab extensively depleted T cells, including more than
1 log reduction in total T cells and more than 3 log reduction in CD4 T cells.
Finally, alemtuzumab decreased HIV-DNA in CD4 T cells by 57% but HIV-DNA remained
detectable at low levels even after depletion of nearly all CD4 T cells.
CONCLUSION: Alemtuzumab extensively depleted multiple T-cell subsets and
decreased the frequency of but did not eliminate HIV-infected CD4 T cells.
Studying the effects on HIV persistence following immune recovery in HIV-infected
individuals who require alemtuzumab for malignancy or in animal studies may
provide further insights into novel cure strategies.
PMID- 28514283
TI - Addressing the Public Health Epidemic of Firearm-related Violence in America.
PMID- 28514284
TI - Comparison in anesthetic effects of propofol among patients with different ABO
blood groups.
AB - Our study was aimed to investigate anesthetic effects of propofol in patients
with different blood groups.A total of 72 participants were enrolled from
patients arranged for surgeries of cholecystectomy, tonsillectomy, and spinal
operation. Each blood group (A, B, AB, and O) contained 18 participants. Mean
arterial pressure (MAP), heart rate (HR), and bispectral index (BIS) were assayed
with Philips monitor. These indexes were observed before propofol anesthesia
(T0), and then were recorded when concentration of propofol was 1 MUg/mL (T1), 2
MUg/mL (T2), 3 MUg/mL (T3), and 4 MUg/mL (T4). The differences in MAP, HR, and
BIS at T0 among groups were compared with the chi test. Multiple comparisons were
adopted to calculate the differences in MAP, HR, and BIS between groups at T1,
T2, T3, and T4.No significant differences in age, sex, and weight of all groups
were found (P > .05). Before propofol anesthesia (T0), all the participants
exhibited no differences in MAP, HR, and BIS (P > .05). Subsequently, we found
obvious differences in DeltaMAP, DeltaHR, and DeltaBIS between groups. The
patients in the B blood group showed highest DeltaMAP and DeltaHR at each time
point (P < .05 for both). As for DeltaBIS, patients in A blood group exhibited
highest value at T3 and T4 (P < .05).The blood group remarkably affects the
anesthetic effects of propofol.
PMID- 28514285
TI - Association of ABCB1 C3435T polymorphism with the susceptibility to osteonecrosis
of the femoral head: A meta-analysis.
AB - BACKGROUND AND OBJECTIVE: The exploration for the etiology of osteonecrosis of
the femoral head (ONFH) has got some promising findings, but the morbidity of
ONFH is still not under control. The C3435T polymorphism of ATP-binding cassette
subfamily B member 1 (ABCB1) gene has been reported to possess significant
influence on ONFH onset, but relevant outcomes remain conflicting rather than
conclusive. Therefore, a meta-analysis was useful to pool these results together
for a more reliable conclusion. METHODS: The association of ABCB1 C3435T
polymorphism with ONFH susceptibility was estimated through calculated odds
ratios (ORs) with their 95% confidence intervals (95% CIs). The Q-test was
applied for detecting inter-study heterogeneity, whereas sensitivity analysis for
identifying any study owning substantial influence on pooled results. Begg's
funnel plot and Egger's test were employed to examine publication bias across
included studies. RESULTS: ABCB1 C3435T polymorphism significantly decreased the
risk of ONFH under TT vs CC (OR = 0.26, 95% CI = 0.13-0.50), TT+CT vs CC (OR =
0.72, 95% CI = 0.52-0.99), TT vs CC+CT (OR = 0.28, 95% CI = 0.15-0.52), and T vs
C (OR = 0.64, 95% CI = 0.50-0.81) contrasts. CONCLUSION: The variant C3435T in
the ABCB1 gene may offer protection against the attack of ONFH, and more studies
with larger sample sizes should be conducted to certify this issue.
PMID- 28514286
TI - Trends in diagnosis of painful neck and back conditions, 2002 to 2011.
AB - Neck and back pain are pervasive problems. Some have suggested that rising
incidence may be associated with the evidence of rising prevalence.To describe
the trends in diagnosis of painful neck and back conditions in a large national
healthcare system.A retrospective observational cohort study to describe the
incidence and prevalence of diagnosis of neck and back pain in a national
cohort.Patients were identified by International Classification of Diseases, 9
Revision (ICD-9) codes in Department of Veterans Affairs (VA) national
utilization datasets in calendar years 2002 to 2011.Descriptive statistics were
used to analyze the data. Prevalent cases were compared with all veterans who
sought health care in each year. Incident cases were identified following a 2
years clean period in which the patient was enrolled and received care, but not
services for any back or neck pain conditions.From 2004 to 2011, 3% to 4% of the
population was diagnosed with incident back pain problems, the rate increasing on
average, 1.75% per year. During the same period, 12.3% to 16.2% of the population
was diagnosed with a prevalent back pain problem, the rate increasing on average
4.09% per year.In a national population, the prevalence rate for diagnosis of
neck and back pain grew 1.8 to 2.3 times faster than the incidence rate. This
suggests that the average duration of episodes of care is increasing. Additional
research is needed to understand the influences on the differential rate of
change and to develop efficient and effective care systems.
PMID- 28514287
TI - Concurrent IgG4-related tubulointerstitial nephritis and IgG4 myeloperoxidase
anti-neutrophil cytoplasmic antibody positive crescentic glomerulonephritis: A
case report.
AB - RATIONALE: IgG4-related disease (IgG4-RD) is a newly recognized systemic disease.
The typical pathological finding in the kidney is abundant IgG4-positive plasma
cell infiltration with characteristic storiform fibrosis in the interstitium.
Antibodies of the IgG4 subclass have been linked to certain autoimmune diseases
including antiproteinase 3 (PR3) anti-neutrophil cytoplasmic antibody (ANCA) of
the IgG4 subclass. Here, we report a rare case of kidney injury with concurrent
typical IgG4-related tubulointerstitial nephritis and IgG4 subclass of
myeloperoxidase (MPO) ANCA-positive necrotizing crescentic glomerulonephritis.
PATIENT CONCERNS: A 42-year-old Chinese man presented with repeated epigastric
pain, sausage-shaped pancreas observed morphologically in computed tomography,
effectiveness of prednisone therapy and was diagnosed with autoimmune
pancreatitis. He subsequently developed acute kidney injury. DIAGNOSES: The
patient had an elevated serum IgG4, eosinophilia, and positive MPO-ANCA of IgG4
dominant subclass. Renal biopsy revealed necrotizing crescentic nephritis and
typical IgG4-related tubulointerstitial nephritis. INTERVENTIONS: The patient was
treated with a combination of corticosteroids and cyclophosphamide, and a course
of rituximab was later added to deplete peripheral B cells. OUTCOMES: The patient
responded well and his renal function improved. LESSONS: This is the first case
report of an IgG4-RD with concurrent IgG4-related tubulointerstitial nephritis
and IgG4 MPO-ANCA-associated necrotizing crescentic glomerulonephritis. It raises
the difficulty in differentiation diagnosis of the two separate diseases that is
worthy of further study.
PMID- 28514288
TI - Bordetella parapertussis outbreak in Southeastern Minnesota and the United
States, 2014.
AB - Whooping cough is traditionally ascribed to Bordetella pertussis; however,
Bordetella parapertussis can cause a similar clinical syndrome. This study
describes an outbreak of B. parapertussis in Southeastern Minnesota and the
United States (US) in 2014. This was a retrospective analysis of Mayo Clinic and
Mayo Medical Laboratories patients who tested positive for B. parapertussis from
2012 to 2014. The medical records of Mayo Clinic patients who tested positive in
2014 were reviewed for demographic information, presenting symptoms, disease
course, and vaccination history. In Southeast Minnesota, 81% of the 31 patients
who tested positive for B. parapertussis in 2014 were found to be positive from
October through December. Their mean age was 5.9 years. Five reported "exposure
to pertussis." Two pairs of siblings were affected. Patients reported having had
symptoms for an average of 2.6 weeks before nasopharyngeal specimen collection
for B. parapertussis testing. Cough was the primary symptom reported. Forty
percent reported posttussive vomiting, 40% coryza, 32% apnea/sleep disturbance,
and 12% sore throat. All were current with pertussis vaccination. Based on the
review of national data, an outbreak occurred nationally in the Northeast and
Midwest US over the same time period. In 2014, there was an outbreak of B.
parapertussis in Southeastern Minnesota and likely other parts of the US. The
presenting illness was similar to that of B. pertussis. All patients were
vaccinated against pertussis, suggesting that pertussis vaccination is
ineffective against B. parapertussis.
PMID- 28514289
TI - Anti-angiogenic therapy with contrast-enhanced ultrasound in colorectal cancer
patients with liver metastasis.
AB - The aim of the study was to evaluate the efficacy of anti-angiogenic therapy with
dynamic contrast-enhanced ultrasound (DCE-US) in colorectal cancer (CRC) patients
with liver metastasis.A total of 50 CRC patients with liver metastasis who
received bevacizumab (BEV)-based chemotherapy (BEV + FOLFOX6 protocol) were
recruited into the present study. Before the study (d0), and 3, 7, 14, and 42
days (d3, d7, d14, and d42) after chemotherapy, DCE-US was performed, and tumor
perfusion was evaluated quantitatively by retention time (RT), peak enhancement
(PE), and wash-in area under the curve (WiAUC) on the basis of a contrast-uptake
curve determined with original linear data.Routine ultrasonography was used to
evaluate metastatic foci in the liver at baseline. A metastatic focus was
selected for dynamic monitoring with ultrasound. The metastatic foci were 1.5 to
8 cm (median: 2.5 cm). The results of hemodynamics monitored at different time
points, including RT, PE, and WiAUC, showed that RT at baseline was significantly
different between groups (P < .001; Responder group: 10.54 seconds; nonresponder
group: 15.33 seconds). The2 groups had opposite changes in RT (continuous
increase in the responder group and transient reduction in the nonresponder). The
RT of metastatic foci was normalized to that of adjacent normal liver as standard
RT-quotient, a similar trend was observed, and no marked difference was noted in
the standard RT-quotient between the 2 groups. The median progression-free
survival was significantly higher in the increased-RT group (10.8 months) than
the decreased-RT group (2.5 months) (P = .002). There were no significant
differences in peak intensity and WiAUC between the 2 groups.DCE-US can be used
to quantitatively evaluate the hemodynamics of liver metastasis in CRC patients
who received bevacizumab-based chemotherapy.
PMID- 28514290
TI - The relationship between iodine intake and the risk of thyroid cancer: A meta
analysis.
AB - Thyroid cancer (TC) is the most common malignancy of the endocrine system. The
relationship between iodine intake and TC risk is controversial always. We aim to
figure out the relationship between iodine intake and TC using meta-analysis.
Literature research in MEDLINE, Embase, China National Knowledge Infrastructure,
and China BioMedicine was performed up to April 2016, searched for relevant case
control and cohort studies. The effect of iodine consumption on the risk of TC
was assessed using the pooled odds ratio (OR) and 95% confidence interval (CI).
The meta-analysis included 8 case-control studies (n = 4974; 2213 cases; 2761
controls). More than adequate or excess iodine intake (>300 MUg/d) decreased the
risk of TC (OR 0.74, 95% CI 0.60, 0.92). High consumption of saltwater fish or
shellfish decreased the risk of TC (OR 0.72, 95% CI 0.55, 0.95; OR 0.70, 95% CI
0.52, 0.96; respectively). A higher intake of dietary iodine was as a protective
factor for TC. However, the available data are very limited and more studies are
required.
PMID- 28514291
TI - Role of microRNA-130a in the pathogeneses of obstructive sleep apnea hypopnea
syndrome-associated pulmonary hypertension by targeting the GAX gene.
AB - OBJECTIVE: The purpose of this study was to elucidate the role of microRNA-130a
(miR-130a) in obstructive sleep apnea hypopnea syndrome (OSAHS)-associated
pulmonary hypertension (PHT) by targeting the growth arrest-specific homeobox
(GAX) gene. METHODS: A total of 108 patients with OSAHS-associated PHT were
recruited as the OSAHS-associated PHT group and 110 healthy individuals were
randomly selected as the normal control group. Human umbilical vein endothelial
cells (HUVECs) were selected and divided into the control, miR-130a mimic, mimic
negative control (NC), miR-130a inhibitor, and inhibitor-NC groups. The dual
luciferase reporter gene assay was used to identify the relationship between miR
130a and the GAX gene. The quantitative real-time polymerase chain reaction (qRT
PCR) and Western blotting were applied for the relative expressions of miR-130a
and the mRNA and protein expressions of GAX. Serum levels of endothelin-1 (ET-1),
vascular endothelial growth factor (VEGF), nitric oxide (NO), and super oxide
dismutase (SOD) were detected. Cell apoptosis and angiogenic activity were
analyzed by flow cytometry and cell tube formation assay. RESULTS: GAX was a
target gene of miR-130a. Compared with the normal control group, the relative
expression of miR-130a and the serum levels of ET-1 and VEGF were increased,
whereas the mRNA expression of GAX and the serum levels of NO and SOD were
decreased in the OSAHS-associated PHT group. Compared with the control, mimic-NC,
and inhibitor-NC groups, the relative expressions of miR-130a in the miR-130a
mimic group were enhanced, whereas the expression of miR-130a in the miR-130a
inhibitor group was reduced. However, the mRNA and protein expressions of GAX
showed an opposite trend in the miR-130a mimic and miR-130a inhibitor groups. In
comparison to the control, mimic-NC, and inhibitor-NC groups, the miR-130a mimic
group had an increase of ET-1 and VEGF expressions, whereas the expressions of NO
and SOD were reduced. However, the miR-130a inhibitor group exhibited an opposite
trend. The apoptosis rate and tube formation number in the miR-130a mimic group
were obviously increased, whereas the miR-130a inhibitor group showed an obvious
decrease. CONCLUSION: These data provided strong evidence that miR-130a may be
involved in the progression of OSAHS-associated PHT by down-regulating GAX gene.
PMID- 28514292
TI - Isolated olecranon fractures in children affected by osteogenesis imperfecta type
I treated with single screw or tension band wiring system: Outcomes and pitfalls
in relation to bone mineral density.
AB - The purpose of this study is to compare the results of 2 techniques, tension band
wiring (TBW) and fixation with screws, in olecranon fractures in children
affected with osteogenesis imperfecta (OI) type I. Between 2010 and 2014, 21
olecranon fractures in 18 children with OI (average age: 12 years old) were
treated surgically. Ten patients were treated with the screw fixation and 11 with
TBW. A total of 65% of olecranon fractures occurred as a result of a spontaneous
avulsion of the olecranon during the contraction of the triceps muscle. The
average follow-up was 36 months. Among the children treated with 1 screw, 5
patients needed a surgical revision with TBW due to a mobilization of the screw.
In this group, the satisfactory results were 50%. In patients treated with TBW,
the satisfactory results were 100% of the cases. The average Z-score, the last
one recorded in the patients before the trauma, was -2.53 in patients treated
with screw fixation and -2.04 in those treated with TBW. TBW represents the
safest surgical treatment for patients suffering from OI type I, as it helps to
prevent the rigidity of the elbow through an earlier recovery of the range of
motion, and there was no loosening of the implant. In analyzing the average Z
score before any fracture, the fixation with screws has an increased risk of
failure in combination with low bone mineral density.
PMID- 28514293
TI - The role of circulating miR-146a in patients with rheumatoid arthritis treated by
Tripterygium wilfordii Hook F.
AB - Rheumatoid arthritis (RA) is polygenic autoimmune disease with unclear etiology.
MicroRNAs (miRNAs) play a critical role in the pathogenesis of RA. The objective
of this study was to evaluate the role of miR-146a in patients with RA receiving
Tripterygium wilfordii Hook F (TwHF) treatment.In total, 69 patients with RA and
69 healthy controls (HC) were included in the study, and patients with RA
received TwHF treatment for 24 weeks. Blood samples were collected from RA
patients and HC, and peripheral blood mononuclear cells (PBMCs) were isolated.
Expression of miR-146a was analyzed in RA patients (baseline, 12 weeks and 24
weeks) and HC.Circulating miR-146a expression was markedly increased in patients
with RA compared with healthy controls (P < .001), ROC analysis of miR-146a for
diagnosis for RA showed that the AUC was 0.908 (95% CI: 0.862-0.955) with a
sensitivity of 87.0% and a specificity of 82.6% at best cutoff. And miR-146a
expression was positively associated with the DAS28 score and CRP level (P = .002
and P = .019). Moreover, miR-146a expression was markedly reduced after TwHF
therapy (P < .001), and baseline miR-146a level was observed to present an
increased tendency in responders compared with non-responders at 24 weeks (P =
.066).Our study presented that circulating miR-146a level was correlated with
risk and disease activity of RA patients by TwHF treatment, which could
strikingly decrease expression of miR-146a in RA patients, and miR-146a may have
a value in predicting clinical response of TwHF treatment. It indicates that
circulating miR-146a plays a prominent role in RA patients treated by TwHF.
PMID- 28514294
TI - TNFAIP3 gene rs7749323 polymorphism is associated with late onset myasthenia
gravis.
AB - In this study, we intended to genotype 2 single nucleotide polymorphisms (SNPs)
of tumor necrosis factor alpha-induced protein 3 (TNFAIP3) genes and explore an
association of TNFAIP3 genetic polymorphism with the patients of myasthenia
gravis (MG) at clinical level. In brief, 215 of adult MG patients were divided
into subgroups according to their clinical features, age of onset, thymic
pathology, and autoantibodies. Two hundred thirty-five of healthy controls were
also divided into subgroups with gender- and age-matched. The allele and genotype
frequencies of subgrouped patients were found to be higher than those of healthy
controls. The distribution of TNFAIP3 gene rs7749323*A allele of late onset MG
(LOMG, with positive acetylcholine receptor antibody and without thymoma)
subgrouped patients was also significantly higher than that of gender- and age
matched healthy controls (7.4% vs 2.4%, odds ratio [OR] = 3.27, 95% confidence
interval [CI] 1.01-10.6, P = .04). Furthermore, analysis to the genotype
frequencies indicates that the carriers of rs7749323*A allele of LOMG group
became more frequent than that of age-matched healthy controls (14.9% vs 4.8%, OR
= 3.47, 95% CI 1.04-11.6, dominant model: P = .03). It is interesting to notice
that there is no significant association between the rs7749323 and susceptibility
of other MG subgroups. Therefore, it is suggested that the SNPs in the 3'
flanking region (rs7749323) of TNFAIP3 gene and the genetic variations of TNFAIP3
gene may take an important role in the susceptibility of LOMG.
PMID- 28514295
TI - Cell death biomarker M65 is a useful indicator of liver inflammation and fibrosis
in chronic hepatitis B: A cross-sectional study of diagnostic accuracy.
AB - Cell death markers, M65 and M30, have been suggested to be sensitive markers of
liver inflammation and fibrosis in nonalcoholic fatty liver disease and chronic
hepatitis C. Our aim was to investigate whether these markers were useful in
diagnosing liver inflammation and fibrosis in chronic hepatitis B (CHB).We
examined 186 patients with CHB; 18 sex- and age-matched healthy subjects were
controls. The blood samples were collected from CHB patients within 1 week before
or after liver biopsy. According to METAVIR score system, liver inflammation was
graded from A0 to A3, and fibrosis from F0 to F4.Serum M65 and M30 levels were in
parallel with the grades of liver inflammation. M65, not M30, increased
significantly in patients with severe inflammation and normal alanine
aminotransferase. M65 is one of the independent predictors of severe liver
inflammation (>=A2). The levels of M65 and M30 levels significantly increased in
parallel with the degree of inflammation in F1 patients, whereas they showed no
statistical difference between different stages of fibrosis in A1 patients.Serum
M65 is a useful indicator of liver inflammation in CHB patients. Serum M65, not
M30, is valuable in the grading of liver fibrosis.
PMID- 28514296
TI - Clinicopathological features and differential diagnosis of aggressive angiomyxoma
of the female pelvis: 5 case reports and literature review.
AB - Aggressive angiomyxoma (AAM) is a rare mesenchymal tumor that usually occurs in
the pelvis and perineum of young females. AAM can simulate Bartholin's gland
cyst, abscess, lipoma, simple labial cyst, or other pelvic soft tissue tumors.
Here we present five cases of AAM with mean age of 42. The patients mainly
presented slow-growing mass in the abdomen and perineum (3 cases in the pelvis, 1
in the vulva, and 1 in the buttock). Color Doppler flow imaging revealed blood
flow for the 3 pelvic lesions. Enhanced computed tomography and magnetic
resonance imaging of the other 2 cases showed the typical "swirled" or "layered"
structure characteristic. Through the pathological examination, its positivity to
estrogen and progesterone receptors can justify enlargement and recurrence,
confirming the tumor is AAM. All 5 patients underwent local tumor resection. Two
patients recurred 8 and 15 months after surgery, respectively. The longest follow
up was 42 months. Although few cases are reported, early recognition demands high
index of suspicion for both gynaecologists and pathologists. Wide surgical
excision with tumor free margins is the basis of curative treatment. Adjuvant
therapy may be necessary for residual or recurrent tumors. Long-term follow-up is
recommended.
PMID- 28514297
TI - Association of single-nucleotide polymorphisms in toll-like receptor 2 gene with
asthma susceptibility: A meta-analysis.
AB - BACKGROUND: An increasing number of studies have been carried out on the
relationship between polymorphisms in toll-like receptor 2 (TLR2) gene and asthma
risk. However, the results were controversial. With the purpose of yielding a
more reliable estimation of the association, we conducted the present meta
analysis. METHODS: Multiple electronic databases up to August 22, 2016 were
searched for literature retrieval. The association between the asthma
susceptibility and the rs5743708 polymorphism, rs3804099 polymorphism, rs3804100
polymorphism, and rs4696480 polymorphism in TLR2 gene was appraised. The odds
ratios (ORs) with 95% confidence intervals (CIs) under different genetic models
were calculated. RESULTS: A total of 13 studies were eligible in our meta
analysis according to the predefined inclusion and exclusion criteria. There was
no significant association between asthma risk and rs5743708, rs3804099, and
rs3804100 polymorphisms in TLR2 gene under any genetic model. With respect to the
TLR2 rs4696480 polymorphism, significant association was detected between asthma
susceptibility and TLR2 rs4696480 polymorphism under dominant model (OR = 2.455,
95% CI = 1.235-4.88, P = .01) and codominant 3 model (OR = 2.776, 95% CI = 1.199
6.427, = 0.017). CONCLUSIONS: Our meta-analysis reveals that the TLR2 rs4696480
polymorphism is significantly associated with asthma susceptibility, and the TLR2
rs4696480 polymorphism is a risk factor for asthma.
PMID- 28514298
TI - Association between common polymorphisms in ERCC gene and glioma risk: A meta
analysis of 15 studies.
AB - BACKGROUND: A number of studies have investigated the roles of excision repair
cross complementation group 1 (ERCC1), ERCC2, and ERCC5 genes polymorphisms in
the development of glioma; however, the results were inconsistent. Here, we
performed a meta-analysis to investigate the association between 6 polymorphisms
in the ERCC genes (rs3212986, rs11615, rs13181, rs1799793, rs238406, rs17655) and
glioma risk. METHODS: The PubMed, Embase, and Web of science were searched up to
September 6, 2016, for studies on the association between ERCC polymorphisms and
glioma risk. A fixed-effects or random-effects model was used to calculate the
pooled odds ratios based on the results from the heterogeneity tests. Sensitivity
and cumulative meta-analyses were also performed. RESULTS: A total of 15 studies
were eligible for the pooled analysis, conducted in 2 populations of ethnic
descent: 8 Europeans and 7 Asians. The results showed that ERCC1 rs3212986
polymorphism was positively associated with glioma [AA vs CC: odds ratio (OR) =
1.298, 95% confidence interval (95% CI) = 1.043-1.230, P = .025]. Association of
the ERCC2 rs13181 and rs1799793 polymorphisms was only observed in Asians (CC vs
AA for rs13181: OR = 1.539, 95% CI = 1.122-2.109, P = .007; AA vs GG for
rs1799793: OR = 1.474, 95% CI = 1.090-1.994, P = .012). However, no association
was observed between glioma risk and ERCC1 rs11615, ERCC2 rs238406, and ERCC5
rs17655 polymorphisms. Moreover, sensitivity and cumulative meta-analyses
confirmed the stability of the results. CONCLUSIONS: Our meta-analysis indicated
that the ERCC1 rs3212986 polymorphism and 2 polymorphisms in ERCC2 gene (rs13181
and rs1799793) contributed to the susceptibility of glioma.
PMID- 28514299
TI - Application of a buprenorphine transdermal patch for the perioperative analgesia
in patients who underwent simple lumbar discectomy.
AB - This study aimed to investigate the perioperative analgesic effect of a
buprenorphine transdermal patch in patients who underwent simple lumbar
discectomy.In total, 96 patients were randomly divided into parecoxib intravenous
injection (Group A), oral celecoxib (Group B), and buprenorphine transdermal
patch groups (Group C). The pain status, degree of satisfaction, adverse effects,
and condition in which the patient received tramadol hydrochloride for
uncontrolled pain were recorded on the night before surgery, postoperative day 1,
postoperative day 3, and postoperative day 5.The degree of patient satisfaction
in Group C was higher than that in Groups A and B, with minimal adverse
effects.The buprenorphine transdermal patch had a better perioperative analgesic
effect in patients who underwent simple lumbar discectomy.
PMID- 28514300
TI - Increasing efficacy and reducing side effects in treatment of chronic anal
fissures: A study of topical diazepam therapy.
AB - This is a single institution nonexperimental study intended to analyze the
therapeutic efficacy of topical diazepam in treating symptoms of chronic anal
fissures.Anal fissures are a common cause of anal pain. Conventional treatments
include nonsteroidal anti-inflammatory drugs, topical creams, such as
nitroglycerin and nifedipine, and surgery. However, these treatments are usually
suboptimally efficacious or have deterring side effects.Patients at an outpatient
community center with a diagnosis of a chronic anal fissure were prescribed
either topical 2% (n = 19) or 4% (n = 18) diazepam cream between January 2013 and
February 2015. We retrospectively analyzed their responses to treatment.All 19
patients using 2% diazepam cream experienced a positive response in pain, whereas
47.4% experienced a complete response, with a numerical rating scale (NRS) score
of 0 (0-10). Eighty-eight percent of patients using 4% dose had a positive
response in pain, whereas 23.5% experienced a complete response. Ninety-four
percent of patients using 2% dose had a positive response in anal bleeding,
whereas 68.8% experienced a complete response with an anal bleeding score (ABS)
of 2 (2-9). Ninety-four percent of patients using 4% dose had a positive response
in anal bleeding, whereas 64.7% experienced a complete response. Only 1 patient
reported a side effect from diazepam cream-perianal pruritus.Both 2% and 4%
topical diazepam provided significant pain and bleeding relief from chronic anal
fissures that were refractory to conventional therapies. There were insignificant
differences when assessing independent comparisons for pain and bleeding between
the doses.
PMID- 28514301
TI - Unusual axillary metastasis of recurrent nasopharyngeal cancer: A case report.
AB - RATIONALE: Nasopharyngeal carcinoma (NPC) has a high propensity of metastasis.
The most commonly described sites of distant metastasis are the bones, lungs, and
liver, whereas axillary metastasis is seldom reported. PATIENT CONCERNS: We
hereby present the case of a 66-year-old man with NPC, cT2N2M0, at diagnosis. He
had completed chemoradiotherapy and been disease-free for 7 years. DIAGNOSES:
After that period, late recurrence in the form of a solitary axillary lymph node
metastasis was detected and confirmed by core-needle biopsy. INTERVENTIONS: The
lesion was chemoresistant but responded to salvage radiotherapy at a dose of 65
Gy in 21 fractions. OUTCOMES: Post-radiotherapy positron emission tomography scan
showed no evidence of disease. LESSONS: We suggested that long-term follow-up of
NPC patients is important because a late relapse may occur at an unusual site.
Aggressive management of solitary metastasis may achieve good outcome.
PMID- 28514302
TI - Safety and efficacy evaluation of pertuzumab in patients with solid tumors.
AB - BACKGROUND: The development of targeted therapies benefits patients with certain
markers in the treatment of breast cancer. Pertuzumab is a novel humanized
monoclonal antibody that blocks human epidermal growth factor receptor 2 (HER2)
dimerization. The Food and Drug Administration has approved pertuzumab in
combination with trastuzumab and docetaxel for the treatment of patients with
HER2-positive metastatic breast cancer. METHODS: To assess the safety and
efficacy profile of pertuzumab, we searched PubMed and Embase (articles from
January 1966 to January 2015) using the keyword "pertuzumab". RESULTS: Fourteen
eligible studies were included in our final analysis. From the results of our
analysis, diarrhea (56.9%, 95% confidence interval [CI] 49.6%-63.9%), nausea
(34.0%, 95% CI 27.7%-40.8%), and rash (25.6%, 95% CI 20.8%-31.0%) were the most
common adverse effects in pertuzumab alone and pertuzumab-based therapies. Based
on randomized controlled clinical trials, diarrhea (odds ratio [OR] 2.310, 95% CI
1.818-2.936), rash (OR 1.848, 95% CI 1.094-3.122), and febrile neutropenia (OR
1.672, 95% CI 1.130-2.474) were of statistical significance, which meant that
pertuzumab played a prominent role in the incidence of diarrhea. Meanwhile,
pertuzumab showed its effective role in cancer control and lifetime prolongation.
CONCLUSION: In conclusion, considering that the common adverse effects for
pertuzumab are gastrointestinal and skin toxicities, which are easier to handle
than other toxicities, pertuzumab is a safe and effective drug for patients with
solid tumors.
PMID- 28514303
TI - Continuous venovenous hemofiltration in the management of paraquat poisoning: A
meta-analysis of randomized controlled trials.
AB - BACKGROUND: Paraquat (PQ) poisoning is a widespread occurrence, especially in
underdeveloped areas. The treatment of PQ poisoning has always been difficult,
and there is currently no definite effective treatment. Continuous venovenous
hemofiltration (CVVH) treatment for PQ poisoning has been widely used in clinical
practice; however, its effect remains uncertain. Accordingly, the purpose of this
meta-analysis was to evaluate the efficacy of CVVH in the treatment of PQ
poisoning. METHODS: We searched for relevant trials using PubMed, Embase, the
Cochrane Library, and 3 Chinese databases, the Chinese BioMedical Literature
Database, National Knowledge Infrastructure Database, and Wanfang Database. We
included all qualified randomized controlled trials (RCTs) of CVVH treatment for
patients with PQ poisoning. The primary outcome was mortality, while the
secondary outcomes included the survival time and constituent ratios of death due
to respiratory failure and circulatory failure. RESULTS: Three RCTs involving 290
patients were included. The mortality rates of the intervention and control
groups were 57.9% and 61.0%, respectively. Pooled analysis demonstrated no
significant difference in mortality between the CVVH treatment and control groups
(risk ratio [RR] 0.94, 95% confidence interval [CI]: 0.78-1.15, P = .56), with a
low level of heterogeneity (X = 1.75, I = 0%). However, the CVVH group was
associated with a longer survival time compared to the control group (weighted
mean difference 1.73, 95% CI: 0.56-2.90, P = .004). Respiratory failure as the
cause of death was more common in the CVVH group, as compared with the control
group (RR 1.66, 95% CI: 1.24-2.23, P = .0008), whereas patients in the control
group were more likely to die from circulatory failure than in the CVVH group (RR
0.56, 95% CI: 0.40-0.81, P = .002). CONCLUSION: Although CVVH treatment might not
noticeably reduce mortality for patients with PQ poisoning, it can prolong the
survival time of the patients and improve the stability of the circulatory
system, thereby enabling further treatment.
PMID- 28514304
TI - Diagnostic and clinical application value of magnetic resonance imaging (MRI) for
progressive massive fibrosis of coal worker pneumoconiosis: Case reports.
AB - RATIONALE: Using magnetic resonance imaging (MRI), we diagnosed pneumoconiosis by
identifying the content and distribution of hydrogen protons in the water
molecules in different tissues and lesions. PATIENT CONCERNS: 25 cases of CWP
patients with progressive massive fibrosis (PMF) lesions. DIAGNOSES: Patients
were correctly diagnosed, with one case each of Phase I and II pneumoconiosis and
23 cases of Phase III pneumoconiosis. INTERVENTIONS: None. OUTCOMES: Through MRI,
39 PMF pneumoconiosis lesions exhibited equal, low or equally low, and uneven
signals on T2WI and fat suppression (SPIR) (38/39, 37/39). LESSONS: MRI has good
specificity to identify the characteristics of PMF lesions of CWP, as well as has
high application value for the differential diagnosis of lung cancer and other
lung tumor-like lesions.
PMID- 28514305
TI - Explaining trends and variation in timing of dialysis initiation in the United
States.
AB - The United States Renal Data System (USRDS) registry of end-stage renal disease
has often been used to study the timing of dialysis initiation, measured by
estimated glomerular filtration rate (eGFR) at dialysis initiation. We conducted
an observational study and examined how well variables in the USRDS database
explain the trends and variation in eGFR at dialysis initiation.We identified
971,481 patients who initiated dialysis between 1995 and 2012 in the USRDS
registry.The mean eGFR at dialysis initiation monotonically rose from 7.7 in 1995
to 11.1 in 2009, and then leveled off to 10.9 mL/min/1.73 m in 2012. The trend of
rising, then leveling off was similar across all subgroups studied. Substantial
variation in eGFR at dialysis initiation was observed, with standard deviation of
4.38 (95% CI: 2.0-18.4). A total of 11.4% of the total variation occurred across
physicians and 88.6% within physicians. Adjustment for measured factors only
modestly decreased the total variation. Of the total variance, 10.7% was
explained by measured patient-level variables and 1.2% by measured physician and
other factors, while 9.2% of physician-level variation and 78.9% of patient-level
variation remained unexplained. The extent of variation explained by measured
variables was similar over the entire study period.The finding that the majority
of variation in eGFR at dialysis initiation is unexplained by measured variables
casts doubt on how well eGFR serves as a measure for "timing" of dialysis
initiation, and it indicates the need to collect more focused data to gain
understanding of factors that affect timing of dialysis initiation in the US.
PMID- 28514306
TI - Unusual case of rapid growing intraabdominal abscess caused by Stenotrophomonas
maltophilia after laparoscopic appendectomy due to perforated appendicitis: A
case report.
AB - INTRODUCTION: An intraabdominal abscess due to Stenotrophomonas maltophilia (S
maltophilia) infection is a very rare clinical manifestation. S maltophilia is a
glucose nonfermentative, aerobic, gram-negative, mobile, and biofilm-forming
bacterium. It is an opportunistic pathogen and uncommon cause of infection.
Respiratory tract infections (pneumonia) and bloodstream infections (bacteremia)
are the most common clinical manifestations of S maltophilia infection.
CONCLUSIONS: This case report describes an unusual case of a rapidly growing,
extremely large intraabdominal abscess (within 1 week during antibiotic therapy),
which was detected 2 weeks after a laparoscopic appendectomy was performed for
perforated appendicitis and was caused by multidrug-resistant S maltophilia
infection.
PMID- 28514307
TI - Exome sequencing identifies a de novo mutation of CTNNB1 gene in a patient mainly
presented with retinal detachment, lens and vitreous opacities, microcephaly, and
developmental delay: Case report and literature review.
AB - RATIONALE: The CTNNB1 (beta-catenin) gene is well known for its crucial role in
cell adhesion and the Wnt-signaling pathway. Previous studies have shown that
gain-of-function mutations in the CTNNB1 gene contribute to the occurrence and
development of a variety of carcinomas in humans. Recently, de novo,
heterozygous, loss-of-function mutations of the CTNNB1 gene were found that
partially explain intellectual disability in some patients. Other major clinical
symptoms in these patients included microcephaly, abnormal facial features, motor
delays, speech impairments, and deformities of the hands and feet. In addition,
approximately 75% of these patients had mild visual defects, such as astigmatism,
hyperopia, or strabismus PATIENT CONCERNS:: A 15-month-old Chinese boy,
presenting with retinal detachment, lens and vitreous opacities, hypertonia of
the extremities, mild thumb adduction, microcephaly, and developmental delay, is
described. Targeted gene sequencing using an ophthalmic gene panel was performed
to test for familial exudative vitreoretinopathy; however, the pathogenic gene
was not found. INTERVENTIONS: Genomic DNA analysis was performed to search for
causing mutations. DIAGNOSES AND OUTCOMES: Whole-exome sequencing revealed a
novel nonsense variation in exon 11 of the CTNNB1 gene (c.1672C>T, p.Gln558X).
Sanger sequencing of the patient and his parent confirmed this mutation and
demonstrated it to be de novo. To the best of our knowledge, this is the first
case report of a loss-of-function mutation of the CTNNB1 gene in an Asian
population. LESSONS: Severe ophthalmic phenotype has not well been connected with
loss of functional mutation of CTNNB1 gene. Our finding expands the mutant
spectrum of CTNNB1 gene and adds new understanding of the phenotype.
PMID- 28514308
TI - Emotional exhaustion-induced latent autoimmune diabetes in adults in a young
lady: A CARE-compliant case report.
AB - RATIONALE: Latent autoimmune diabetes in adults (LADA) refers to an autoimmune
disorder characterized with detectable islets antibodies in the early diagnosis
and increased autoimmune beta-cell failure progression. Notably, this kind of
diabetes seems to be confused with other phenotypic diabetes. PATIENT CONCERNS: A
young woman suffered an emotional exhaustion-induced LADA, showing asthenia,
polydipsia, polyuria, and visible weight loss. The patient emotionally ended a 14
year romantic relationship, leading to the emotional flooding. DIAGNOSES: The
data from physical examination and laboratory tests exhibited as follows:
glutamic acid decarboxylase antibody (GADA) = 63.83 U/mL, the fasting blood
glucose (FBG) = 13.3 mmol/L, and glycated haemoglobin (HbA1c) = 10.9%. According
to levels of GADA, the patient was diagnosed as LADA. INTERVENTIONS: The patient
was clinically treated with insulin for 3-month. Then, running, diet-control, and
emotional treatment were combined, such as the patient started a new
relationship. OUTCOMES: An emotional recovery initiated from a new romantic
relationship and a baby, showing normal levels of GAD65 (27.007 IU/mL) and FBG
(5.46) mmol/L. LESSONS: The emotional exhaustion might play a significant role in
induction of LADA. It is important that individuals should maintain optimism,
cheer, and a positive attitude.
PMID- 28514309
TI - A randomized controlled trial of botulinum toxin A for treating neuropathic pain
in patients with spinal cord injury.
AB - BACKGROUND: To assess the effect of botulinum toxin A (BTA) for treating
neuropathic pain in patients with spinal cord injury (SCI). METHODS: A total of
44 patients with SCI with neuropathic pain were randomly divided into the
intervention group and the placebo group, each group 21 patients. The subjects in
the intervention group received BTA (200 U subcutaneous injection, once daily) at
the painful area, whereas those in the placebo group were administered a saline
placebo. This study was conducted from December 2014 to November 2016. The
primary outcome was measured using the visual analog scale (VAS). The secondary
outcomes were measured using the short-form McGill Pain Questionnaire (SF-MPQ),
and World Health Organization quality of life (WHOQOL-BREF) questionnaire. All
outcome measurements were performed before and after 4 and 8 weeks of
intervention. RESULTS: Forty-one participants completed the study. The
intervention with BTA showed greater efficacy than placebo in decreasing the VAS
score after week 4 and week 8 of treatment. Significant differences in the SF-MPQ
and WHOQOL-BREF were also found between the 2 groups. CONCLUSION: The results of
this study demonstrated that BTA might decrease intractable neuropathic pain for
patients with SCI.
PMID- 28514310
TI - Development and validation of a mortality risk model for pediatric sepsis.
AB - Pediatric sepsis is a burdensome public health problem. Assessing the mortality
risk of pediatric sepsis patients, offering effective treatment guidance, and
improving prognosis to reduce mortality rates, are crucial.We extracted data
derived from electronic medical records of pediatric sepsis patients that were
collected during the first 24 hours after admission to the pediatric intensive
care unit (PICU) of the Hunan Children's hospital from January 2012 to June 2014.
A total of 788 children were randomly divided into a training (592, 75%) and
validation group (196, 25%). The risk factors for mortality among these patients
were identified by conducting multivariate logistic regression in the training
group. Based on the established logistic regression equation, the logit
probabilities for all patients (in both groups) were calculated to verify the
model's internal and external validities.According to the training group, 6
variables (brain natriuretic peptide, albumin, total bilirubin, D-dimer, lactate
levels, and mechanical ventilation in 24 hours) were included in the final
logistic regression model. The areas under the curves of the model were 0.854
(0.826, 0.881) and 0.844 (0.816, 0.873) in the training and validation groups,
respectively.The Mortality Risk Model for Pediatric Sepsis we established in this
study showed acceptable accuracy to predict the mortality risk in pediatric
sepsis patients.
PMID- 28514311
TI - Trends in esophageal and esophagogastric junction cancer research from 2007 to
2016: A bibliometric analysis.
AB - BACKGROUND: This study aimed to analyze the scientific outputs of esophageal and
esophagogastric junction (EGJ) cancer and construct a model to quantitatively and
qualitatively evaluate pertinent publications from the past decade. METHODS:
Publications from 2007 to 2016 were retrieved from the Web of Science Core
Collection database. Microsoft Excel 2016 (Redmond, WA) and the CiteSpace (Drexel
University, Philadelphia, PA) software were used to analyze publication outcomes,
journals, countries, institutions, authors, research areas, and research
frontiers. RESULTS: A total of 12,978 publications on esophageal and EGJ cancer
were identified published until March 23, 2017. The Journal of Clinical Oncology
had the largest number of publications, the USA was the leading country, and the
University of Texas MD Anderson Cancer Center was the leading institution. Ajani
JA published the most papers, and Jemal A had the highest co-citation counts.
Esophageal squamous cell carcinoma ranked the first in research hotspots, and
preoperative chemotherapy/chemoradiotherapy ranked the first in research
frontiers. CONCLUSION: The annual number of publications steadily increased in
the past decade. A considerable number of papers were published in journals with
high impact factor. Many Chinese institutions engaged in esophageal and EGJ
cancer research but significant collaborations among them were not noted. Jemal
A, Van Hagen P, Cunningham D, and Enzinger PC were identified as good candidates
for research collaboration. Neoadjuvant therapy and genome-wide association study
in esophageal and EGJ cancer research should be closely observed.
PMID- 28514313
TI - Clinical and biological correlations in celiac disease in children: the
prospective single experience of a romanian tertiary center: A case-control study
(Strobe-Compliant study).
AB - Celiac disease-a chronic inflammatory disease of the intestine-is triggered by
gluten or associated protein consumption.The aim of our study was to assess the
sensitivity, specificity of the combined anti-transglutaminase 2 (TG2)/deamidated
gliadin peptide antibodies (DGP), and antiendomisium antibodies (EMA), to
determine the distribution of HLA-DQ2/DQ8 for the 140 tested patients, and also
to evaluate the clinical and laboratory characteristics of patients admitted with
the suspicion of celiac disease (CD). Children included in the study were divided
into: group 1, patients with confirmed CD; group 2, patients with "potential' CD;
group 3, control group, patients without CD. We assessed the standard laboratory
data, the level of TG2/DGP and EMA antibodies, as well as the distribution of HLA
molecules in the selected patients. Histopathological examination was considered
the criterion standard for diagnosis in most cases.The sensitivity of TG2/DGP was
85% and the specificity 92%. EMA showed a sensitivity of 82% and a specificity of
98%. The vast majority of patients diagnosed with CD were either HLA-DQ2.5
(encoded by DQA1*05 & DQB1*02) positive (87.5%) or HLA-DQ8 (encoded by
DQB1*03:02) positive (12.5%). One patient showed a positivity only for HLA-DQ2.2
(encoded by DQA1*02 & B1*02).Our study showed that the genetic risk for CD was
present in more than one-third of the cases without a confirmed diagnosis of CD.
Therefore, the awareness of genetic susceptibility for CD is essential because of
the fact that these individuals can develop the disease at any point of their
lives. The sensitivity of TG2/DGP and EMA were very similar, whereas EMA
presented a higher specificity as that of TG2/DGP.
PMID- 28514314
TI - Infected tibia defect fractures treated with the Masquelet technique.
AB - The treatment after open and infected fractures with extensive soft tissue damage
and bone deficit remains a challenging clinical problem. The technique described
by Masquelet, using a temporary cement spacer to induce a membrane combined with
reconstructive soft tissue coverage, is a possible solution. This study describes
the work-up, operative procedure, complications, and the outcome of a homogenous
group of patients with an open and infected tibia fracture and segmental bone
loss treated with the Masquelet technique (MT).This retrospective study evaluates
patients having sustained an open tibia fracture treated with the MT between 2008
and 2013 with a follow up of at least 1 year. The defect was either primary,
caused by a high-grade open fracture or secondary due to a non-union after an
open fracture. Prerequisite conditions prior to the procedure of the Masquelet
were a defect zone with eradicated infection, an intact soft tissue cover and
stability provided by an external fixation.Volume of the defect, time until the
implantation of the spacer, time of the spacer in situ and the time to clinical
and radiological union were evaluated. Patient records were screened for
reoperations and complications. The functional clinical outcome was
measured.Eight patients were treated with a follow up over 1 year. The spacer was
implanted after a median of 11 (2-70) weeks after the accident. The predefined
conditions for the Masquelet phase were reached after a median of 12 (7-34)
operations.Seven patients required reconstructive soft tissue coverage. The
volume of the defect had a median of 111 (53.9-621.6) cm, the spacer was in situ
for a median of 12 (7-26) weeks. Radiological healing was achieved in 7 cases
after a median time of 52 (26-93) weeks.Full weight bearing was achieved after a
median time of 16 (11-24) weeks. Four patients needed a reoperation. The lower
limb functional index was a median of 60% (32-92%).Seven out of 8 patients
treated in this group of severe open and infected tibia fractures did both
clinically and radiologically heal. Due to the massive destruction of the soft
tissue, patients needed several reoperations with soft tissue debridements and
reconstruction before the spacer and the bone graft could be implanted.
PMID- 28514312
TI - Treatment inferred from mutations identified using massive parallel sequencing
leads to clinical benefit in some heavily pretreated cancer patients.
AB - Molecular portraits of numerous tumors have flooded oncologists with vast amounts
of data. In parallel, effective inhibitors of central pathways have shown great
clinical benefit. Together, this promises potential clinical benefits to
otherwise end-stage cancer patients. Here, we report a clinical service offering
mutation detection of archived samples using the ion Ampliseq cancer panel
coupled with clinical consultation.A multidisciplinary think tank consisting of
oncologists, molecular-biologists, genetic counselors, and pathologists discussed
67 heavily pretreated, advanced cancer patient cases, taking into account
mutations identified using ion Ampliseq cancer panel, medical history, and
relevant literature.The team generated a treatment plan, targeting specific
mutations, for 41 out of 64 cases. Three patients died before results were
available. For 32 patients, the treating oncologists chose not to include the
panel recommendation in the treatment plan for various reasons. Nine patients
were treated as recommended by the panel, 5 with clinical benefit, and 4 with
disease progression.This study suggests that routine use of massive parallel
tumor sequencing is feasible and can judiciously affect treatment decisions when
coupled with multidisciplinary team-based decision making. Administration of
personalized based therapies at an earlier stage of disease, expansion of genetic
alterations examined, and increased availability of targeted therapies may lead
to further improvement in the clinical outcome of metastatic cancer patients.
PMID- 28514316
TI - New idea for treatment strategies for Barcelona Clinic Liver Cancer stages based
on a network meta-analysis.
AB - BACKGROUND: Currently, the Barcelona Clinic Liver Cancer staging (BCLC) system
still remains controversies in the management of hepatocellular carcinoma. We are
trying to determine the best therapeutic strategy for each BCLC stage through a
network meta-analysis and provide a new treatment idea. METHODS: We conducted a
systematic literature search of the PubMed, EMBASE, and Cochrane Library
databases and extracted data from randomized controlled trials (RCTs) that
compared various strategies. Network meta-analyses were conducted in ADDIS by
evaluating different overall survival of each stage. Cumulative probability was
used to rank the included strategies. A node-splitting model assessed whether
direct and indirect evidence on a specific node was in agreement. RESULTS: Of the
24 included RCTs, 3667 patients were included. Based on the probability P values,
the results showed that TACE plus surgical resection (SR) was the first choice
for BCLC Stage A (P = .38 and P = .52 for 3- and 5-year OS, respectively). The
application of SR was the best strategy for BCLC Stage B (P = .51 and P = .95 for
1- and 3-year OS, respectively). For Stage C, whole net connections could not be
established in this research, but combined therapy seemed to produce better
results based on 3 separated net connections (P = .92, P = .80, and P = .69 for 1
year OS). CONCLUSIONS: The updated therapy strategies discussed in this study are
recommended. More importantly, we deemed that the recommended strategy for each
patient may be subject to adjustment due to individual clinical factors. The
applicable scope of each strategy should also be evaluated before application.
PMID- 28514315
TI - Role of Cystatin C and glomerular filtration rate in diagnosis of kidney
impairment in hepatic cirrhosis patients.
AB - Hepatic cirrhosis is often accompanied by functional kidney impairment, which may
be reversed if early treatment is promptly administered. This study aimed to
investigate the role of Cystatin C and Cystatin C estimated glomerular filtration
rate in the diagnosis of kidney impairment in patients with hepatic
cirrhosis.Four hundred sixty five patients with hepatic cirrhosis were recruited.
Serum creatinine and Cystatin C were determined, and their estimated glomerular
filtration rates were calculated.The area under the receiver-operating
characteristic curve (area under curve [AUC]) of Cystatin C and Cystatin C
estimated glomerular filtration rate was significantly larger than that of serum
creatinine and serum creatinine estimated glomerular filtration rate,
respectively (P = .000). When the optimal cut-off value and upper reference limit
were used, similar sensitivity, misdiagnosis rate, and diagnostic consistency
were only observed in Cystatin C estimated glomerular filtration rate (P >
.05).Cystatin C and Cystatin C estimated glomerular filtration rate are superior
to serum creatinine and serum creatinine estimated glomerular filtration rate in
diagnosis of secondary kidney impairment, and Cystatin C estimated glomerular
filtration rate has a better performance as compared with Cystatin C. However, it
is not a measured parameter, and thus the lab should determine its own optimal
cut-off value.
PMID- 28514317
TI - Impact of age on short-term outcomes of liver surgery: Lessons learned in 10
years' experience in a tertiary referral hepato-pancreato-biliary center.
AB - We investigate the surgical outcomes of patients undergoing hepatectomy according
to different age intervals, identify the clinical factors related to surgical
outcomes, and propose clinical risk scores for severe morbidity and mortality
based on the clinical factors.Eight hundred three patients undergoing liver
resection were divided into 3 groups: young patients (YP), <65 years (n = 387),
elderly patients (EP), from 65 to 74 years (n = 279); very-elderly patients
(VEP), >=75 years (n = 137).Severe morbidity was 10.6%, 12.2%, and 17.5% (P =
.103), and mortality was 0.3%, 1.4%, and 4.4% (P = .002) in group YP, EP, and
VEP, respectively. Ischemic heart disease, cirrhosis, major hepatectomy, biliary
tract-associated procedure, and red blood cells (RBC) transfusion >=3 U were
related with severe morbidity. Ischemic heart disease, cirrhosis, major
hepatectomy, and RBC transfusion were independent risk factors for postoperative
mortality. Age did not result an independent factor related to mortality and
severe morbidity. Two different scores were developed and have proved to be
statistically related with severe morbidity and mortality. Moreover, in patients
with score >=2, severe morbidity increased from 24.2% in YP, to 29.3% in EP, and
to 40.0% in VEP, P = .047. Likewise, mortality increased from 2.3% in YP, to 7.0%
in EP, and to 22.7% in VEP, in patients with score >=2, P = .017.Age alone should
not be considered a contraindication for hepatectomy. We identified factors and
proposed 2 scores that can be useful to stratify the risk of morbidity and
mortality after hepatectomy. Moreover, severe morbidity and mortality increases
according to the different age intervals in patients with scores >=2.
PMID- 28514318
TI - Cerebral Oxygen Saturation in Children With Congenital Heart Disease and Chronic
Hypoxemia.
AB - BACKGROUND: Increased hemoglobin (Hb) concentration accompanying hypoxemia is a
compensatory response to maintain tissue oxygen delivery. Near infrared
spectroscopy (NIRS) is used clinically to detect abnormalities in the balance of
cerebral tissue oxygen delivery and consumption, including in children with
congenital heart disease (CHD). Although NIRS-measured cerebral tissue O2
saturation (ScO2) correlates with arterial oxygen saturation (SaO2), jugular bulb
O2 saturation (SjbO2), and Hb, little data exist on the interplay between these
factors and cerebral O2 extraction (COE). This study investigated the
associations of ScO2 and DeltaSaO2-ScO2 with SaO2 and Hb and verified the normal
range of ScO2 in children with CHD. METHODS: Children undergoing cardiac
catheterization for CHD were enrolled in a calibration and validation study of
the FORE-SIGHT NIRS monitor. Two pairs of simultaneous arterial and jugular bulb
samples were drawn for co-oximetry, calculation of a reference ScO2 (REF CX), and
estimation of COE. Pearson correlation and linear regression were used to
determine relationships between O2 saturation parameters and Hb. Data were also
analyzed according to diagnostic group defined as acyanotic (SaO2 >= 90%) and
cyanotic (SaO2 < 90%). RESULTS: Of 65 children studied, acceptable jugular bulb
samples (SjbO2 absolute difference between samples <=10%) were obtained in 57
(88%). The DeltaSaO2-SjbO2, DeltaSaO2-ScO2, and DeltaSaO2-REF CX were positively
correlated with SaO2 and negatively correlated with Hb (all P < .001). Although
by diagnostic group ScO2 differed statistically (P = .002), values in the
cyanotic patients were within the range considered normal (69% +/- 6%). COE
estimated by the difference between arterial and jugular bulb O2 content
(DeltaCaO2-CjbO2, mL O2/100 mL) was not different for cyanotic and acyanotic
patients (P = .10), but estimates using DeltaSaO2-SjbO2, DeltaSaO2-ScO2, or
DeltaSaO2-ScO2/SaO2 were significantly different between the cyanotic and
acyanotic children (P < .001). CONCLUSIONS: Children with adequately compensated
chronic hypoxemia appear to have ScO2 values within the normal range. The
DeltaSaO2-ScO2 is inversely related to Hb, with the implication that in the
presence of reduced Hb, particularly if coupled with a decreased cardiac output,
the ScO2 can fall to values associated with brain injury in laboratory studies.
PMID- 28514319
TI - Prospective External Validation of Three Preoperative Risk Scores for Prediction
of New Onset Atrial Fibrillation After Cardiac Surgery.
AB - BACKGROUND: Postoperative atrial fibrillation (POAF) is associated with early and
late morbidity and mortality of cardiac surgical patients. Prophylactic treatment
of atrial fibrillation (AF) has been recommended to improve outcome in cardiac
surgical patients at high risk of developing POAF. Reliable models for prediction
of POAF are needed to achieve that goal. This study attempted to externally
validate 3 risk models proposed for preoperative prediction of POAF in cardiac
surgical patients: the POAF score, the CHA2DS2-VASc score, and the Atrial
Fibrillation Risk Index. METHODS: This was a prospective cohort study of 1416
adult patients who underwent nonemergent coronary artery bypass graft and/or
valve surgery in a single cardiac surgical center between February 2014 and
September 2015. A risk score for each of the 3 prediction models was calculated
in each patient. All patients were followed for up to 2 weeks, or until hospital
discharge, to observe the primary outcome of new onset AF requiring treatment.
Discrimination was assessed using receiver operating characteristic curves.
Calibration was assessed using the Pearson chi goodness-of-fit test and
calibration plots. Utility of the score to implement AF prophylaxis based on the
risk of POAF, in comparison to strategies of treating all patients, or not
treating any patients, was assessed via a net benefit analysis. RESULTS: Of the
1416 patients included in this study, 478 had the primary outcome (33.8%). The
areas under the receiver operating characteristic curve for prediction of POAF in
the population subsets for which the scores were validated were as follows: 0.651
(95% confidence interval [CI], 0.621-0.681) for the POAF score, 0.593 (95% CI,
0.557-0.629) for the CHA2DS2-VASc score (P < .001 versus POAF score, P < .222
versus Atrial Fibrillation Risk Index), and 0.563 (95% CI, 0.522-0.604) for the
Atrial Fibrillation Risk Index (P < .001 versus POAF score). The calibration
analysis showed that the predictive models had a poor fit between the observed
and expected rates of POAF. Net benefit analysis showed that AF preventive
strategies based on these scores, and targeting patients with moderate or high
risk of POAF, improve decision-making in comparison to preventive strategies of
treating all patients. CONCLUSIONS: The 3 prediction scores evaluated in this
study have limited ability to predict POAF in cardiac surgical patients. Despite
this, they may be useful in preventive strategies targeting patients with
moderate or high risk of PAOF in comparison with preventive strategies applied to
all patients.
PMID- 28514320
TI - Preoperative Warming Versus no Preoperative Warming for Maintenance of
Normothermia in Women Receiving Intrathecal Morphine for Cesarean Delivery: A
Single-Blinded, Randomized Controlled Trial.
AB - BACKGROUND: Rates of hypothermia for women undergoing spinal anesthesia for
cesarean delivery are high and prevention is desirable. This trial compared the
effectiveness of preoperative warming versus usual care among women receiving
intrathecal morphine, which is thought to exacerbate perioperative heat loss.
METHODS: A prospective, single-blinded, randomized controlled trial compared 20
minutes of forced air warming (plus intravenous fluid warming) versus no active
preoperative warming (plus intravenous fluid warming) in 50 healthy American
Society of Anesthesiologists graded II women receiving intrathecal morphine as
part of spinal anesthesia for elective cesarean delivery. The primary outcome of
maternal temperature change was assessed via aural canal and bladder temperature
measurements at regular intervals. Secondary outcomes included maternal thermal
comfort, shivering, mean arterial pressure, agreement between aural temperature,
and neonatal outcomes (axillary temperature at birth, Apgar scores,
breastfeeding, and skin-to-skin contact). The intention-to-treat population was
analyzed with descriptive statistics, general linear model analysis, linear mixed
model analysis, chi test of independence, Mann-Whitney, and Bland-Altman
analysis. Full ethical approval was obtained, and the study was registered on the
Australia and New Zealand Clinical Trials Registry (Trial No: 367160, registered
at http://www.ANZCTR.org.au/). RESULTS: Intention-to-treat analysis (n = 50)
revealed no significant difference in aural temperature change from baseline to
the end of the procedure between groups: F (1, 47) = 1.2, P = .28. There were no
other statistically significant differences between groups in any of the
secondary outcomes. CONCLUSIONS: A short period of preoperative warming is not
effective in preventing intraoperative temperature decline for women receiving
intrathecal morphine. A combination of preoperative and intraoperative warming
modalities may be required for this population.
PMID- 28514321
TI - Patient Blood Management in Major Orthopedic Surgery: Less Erythropoietin and
More Iron?
AB - Erythropoietin (EPO) is proposed preoperatively to reduce blood transfusion in
anemic patients (hemoglobin < 13 g/dL) scheduled for a major orthopedic surgery.
New intravenous iron formulations allow infusion of higher doses, increasing EPO
response. In that context, we evaluated in a before-after study (n = 62 and 65
patients for each period) a new EPO administration protocol (2 injections 4 and 3
weeks before surgery, and a third if hemoglobin <13 g/dL instead of <15 g/dL 2
weeks before surgery). After this protocol implementation, the mean (standard
deviation) number of EPO injections decreased from 2.8 (0.5) to 2.2 (0.4)/patient
(P < .0001) without changing transfusion rates (3% in the 2 periods).
PMID- 28514322
TI - Relationship Between a Sepsis Intervention Bundle and In-Hospital Mortality Among
Hospitalized Patients: A Retrospective Analysis of Real-World Data.
AB - BACKGROUND: Sepsis is a systemic response to infection that can lead to tissue
damage, organ failure, and death. Efforts have been made to develop evidence
based intervention bundles to identify and manage sepsis early in the course of
the disease to decrease sepsis-related morbidity and mortality. We evaluated the
relationship between a minimally invasive sepsis intervention bundle and in
hospital mortality using robust methods for observational data. METHODS: We
performed a retrospective cohort study at the University of California, San
Francisco, Medical Center among adult patients discharged between January 1,
2012, and December 31, 2014, and who received a diagnosis of severe sepsis/septic
shock (SS/SS). Sepsis intervention bundle elements included measurement of blood
lactate; drawing of blood cultures before starting antibiotics; initiation of
broad spectrum antibiotics within 3 hours of sepsis presentation in the emergency
department or 1 hour of presentation on an inpatient unit; administration of
intravenous fluid bolus if the patient was hypotensive or had a lactate level >4
mmol/L; and starting intravenous vasopressors if the patient remained hypotensive
after fluid bolus administration. Poisson regression for a binary outcome
variable was used to estimate an adjusted incidence-rate ratio (IRR) comparing
mortality in groups defined by bundle compliance measured as a binary predictor,
and to estimate an adjusted number needed to treat (NNT). RESULTS: Complete
bundle compliance was associated with a 31% lower risk of mortality (adjusted
IRR, 0.69, 95% confidence interval [CI], 0.53-0.91), adjusting for SS/SS
presentation in the emergency department, SS/SS present on admission (POA), age,
admission severity of illness and risk of mortality, Medicaid/Medicare payor
status, immunocompromised host status, and congestive heart failure POA. The
adjusted NNT to save one life was 15 (CI, 8-69). Other factors independently
associated with mortality included SS/SS POA (adjusted IRR, 0.55; CI, 0.32-0.92)
and increased age (adjusted IRR, 1.13 per 10-year increase in age; CI, 1.03
1.24). CONCLUSIONS: The University of California, San Francisco, sepsis bundle
was associated with a decreased risk of in-hospital mortality across hospital
units after robust control for confounders and risk adjustment. The adjusted NNT
provides a reasonable and achievable goal to observe measureable improvements in
outcomes for patients diagnosed with SS/SS.
PMID- 28514323
TI - Perioperative Care of the Concussed Patient: Making the Case for Defining Best
Anesthesia Care.
PMID- 28514324
TI - Use of the Fluid Challenge in Critically Ill Adult Patients: A Systematic Review.
AB - The fluid challenge (FC) aims at identifying patients in whom fluid
administration improves hemodynamics. Although the FC has been extensively
studied, the implementation and definition of improvement are not standardized.
This systematic review of studies published between January 1, 1994 and December
31, 2014 characterizes these key components of the FC for critically ill adult
patients, as described in the medical literature in the last 20 years. A
literature search was performed using MEDLINE, Embase, and Cochrane. For each
study, data were collected on study design, study size, study setting, patient
population, and how the FC was administered. Eligibility criteria for FC were (1)
the infusion of a definite quantity of fluid, (2) of a specific type, (3) in a
fixed time period (expressed as either span or infusion rate), (4) with a defined
hemodynamic variable as the target, and (5) for a predetermined threshold. One
hundred fifty-seven full-text manuscripts were extracted from 870 potentially
relevant studies. The inclusion criteria were met by 71 studies including 3617
patients. Sixty-six studies were from a single center and 45 were prospective
observational in format. The most common amount infused was 500 cc, used by 55
(77.5%) studies. The most commonly infused fluids were colloids (62.0%). In 43
(60.5%) studies, the FC was administered between 20 and 30 minutes. A positive
response to fluid administration was defined as an increase >=15% of cardiac
index or cardiac output in 44 (62.6%) studies. Static or dynamic physiologic
indices were utilized in a minority of studies (16.9%) and safety limits for
interrupting the FC are adopted in 4 (5.6%) studies only. This systematic review
indicates that the FC most commonly consists in infusing 500 mL of crystalloids
or colloids in 20-30 minutes, and considered an increase in cardiac index >=15%
as a positive response. However, definite standards for FC administration and
evaluation remain undefined.
PMID- 28514325
TI - An Etomidate Analogue With Less Adrenocortical Suppression, Stable Hemodynamics,
and Improved Behavioral Recovery in Rats.
AB - BACKGROUND: ET-26 hydrochloride (ET-26HCl) is a novel etomidate analogue designed
to alleviate the adrenocortical suppression caused by etomidate while retaining
the rapid sedative-hypnotic onset and stable hemodynamic features of etomidate.
This study compared the anesthetic effect, hemodynamic stability, and recovery
profiles of ET-26HCl, etomidate, and the sedative-hypnotic drug propofol in rats.
METHODS: The metabolic half-life of ET-26HCl was determined in vitro using high
performance liquid chromatography analysis of samples of rat plasma and liver
homogenates taken from 3 animals. Hypnotic median effective doses (HD50) of ET
26HCl, etomidate, and propofol were determined by up-and-down methods. Anesthesia
effect and mean arterial pressure were estimated using equivalent intravenous
(IV) doses of propofol, etomidate, and ET-26HCl in the rats. Serum concentrations
of corticosterone were analyzed by enzyme-linked immunosorbent assay. The ability
of rats to recover from the sedative-hypnotic effects of the drugs was evaluated
using open field and Morris water maze tests at equipotent doses of propofol,
etomidate, ET-26HCl, and normal saline. RESULTS: The metabolic half-life of ET
26HCl was 81 +/- 6 minutes in rat plasma and 126 +/- 12 minutes in incubation
liver homogenate (mean +/- standard deviation), respectively. In vivo experiments
showed that the potency of ET-26HCl to cause a loss of righting reflex in rats
was 3 times lower than that of etomidate in the rats. IV propofol caused a
greater decrease in mean arterial pressure relative to the baseline (-27.9 mm Hg)
than did ET-26HCl (-10.7 mm Hg) and etomidate (-19.4 mm Hg) at equipotent doses.
Serum corticosterone levels after drug administration were significantly higher
in the ET-26HCl group than in the etomidate group at equivalent doses when
measured 15 (P < .001), 30 (P < .001), and 60 (P = .002) minutes after
stimulation with adrenocorticotropic hormone (ACTH1-24). Recovery of spatial
orientation from anesthesia induced by an IV bolus injection was faster with ET
26HCl than with propofol, but recovery of spontaneous activity was slower.
CONCLUSIONS: ET-26HCl has anesthetic potency and hemodynamic stability similar to
etomidate, but it caused less adrenocortical hormone synthesis suppression than
etomidate and faster spatial orientation recovery from anesthesia than propofol,
which was similar to etomidate.
PMID- 28514326
TI - Cancellation of Elective Cases in a Recently Opened, Tertiary/Quaternary-Level
Hospital in the Middle East.
AB - Case cancellations have a negative financial impact due to revenue loss and the
potential costs of underutilized time. The goals of this study at a recently
opened hospital in the Middle East were to measure the cancellation rates for
elective surgical or endoscopic cases and to identify the reasons for
cancellation. During the 1-month study period, 170 (22.4%) of the 760 scheduled
cases were cancelled. Cultural norms and patient no-shows on the day of surgery
accounted for the majority of case cancellations. Understanding local factors on
hospital functions may be vital for organizations expanding into new geographic
areas.
PMID- 28514328
TI - [An aging brain: morphofunctional aspects].
AB - A review of main results in the field that are relevant for understanding of the
clinical pathology developed in old age is presented. The authors focus attention
on the characteristics of atrophic processes and their severity in different
brain structures including cognitive impairment (memory etc). Correlations
between structural changes in brain tissues and neurochemical and bioelectrical
processes in the CNS are discussed.
PMID- 28514327
TI - Postoperative Assessment of Myocardial Function and Microcirculation in Patients
with Acute Coronary Syndrome by Myocardial Contrast Echocardiography.
AB - BACKGROUND Postoperative myocardial function and microcirculation of acute
coronary syndrome (ACS) was assessed by myocardial contrast echocardiography
(MCE). MATERIAL AND METHODS Eighty-nine ACS patients treated with percutaneous
coronary intervention (PCI) were detected by MCE and two-dimensional
ultrasonography before and a month later after PCI respectively. Their myocardial
perfusion was evaluated by myocardial contrast score (MSC) and contrast score
index (CSI); cross-sectional area of microvessel (A), average myocardial
microvascular impairment (beta), and myocardial blood flow (MBF) were analyzed by
cardiac ultrasound quantitative analysis (CUSQ), and fractional flow reserve
(FFR) change was observed. Left ventricular ejection fraction (LVEF), left
ventricular end-diastolic dimension (LVEDD), and left ventricular end-systolic
dimension (LVESD) were observed; the index of microcirculatory resistance (IMR),
FFR, and coronary flow reserve (CFR) were detected to evaluate coronary
microcirculation. RESULTS None of the 89 patients experienced no-reflow. Patients
with normal myocardial perfusion mostly had normal or slightly decreased
ventricular wall motion after PCI. A month after the operation, there was an
increase in A, beta, MBF, LVEF, E/A, IMR, FFR, and CFR (all P<0.05), while LVEDD,
LVESD, diastolic gallop A peak, E/Ea, E/Ea*S, and Tei decreased (all P<0.05).
LVEF and IMR were in positive correlations with A. LVEF, IMR, FFR and CFR were
positively correlated with b and MBF (both r>0, P<0.05), while E/Ea*Sa and Tei
were negatively correlated with b and MBF (r<0, P<0.05). CONCLUSIONS MCE can
safely assess post-PCI myocardial function and microcirculation of ASC.
PMID- 28514329
TI - [Brain plasticity: limitations and possibilities].
AB - Biological limitations related to the brain regeneration and stem cells
transplantation as well as the factors influencing the brain plasticity following
the brain injury, including epigenetic regulatory mechanisms, are presented. Non
invasive transcranial microelectrostimulation is considered as a perspective
method of polysystemic influence on endogenic mechanisms of brain recovery.
PMID- 28514330
TI - [MRI morphometry of neuroplastic changes in the brain after conservative
treatment of traumatic brachial plexopathy].
AB - AIM: To identify neuroplastic changes in the brain structures during treatment of
traumatic axonotomy of the brachial plexus (the pathology of peripheral nervous
system). MATERIAL AND METHODS: MRI morphometry of white and grey matter was
studied in 62 patients with traumatic axonotomy of the brachial plexus. RESULTS:
There were correlations between the thickness of sensorimotor cortex,
morphometric parameters (volume, diffusion, fractional anisotropy) of subcortical
formations (corticospinal tracts, the forceps minor), severity of neurological
deficit and dynamics of clinical course depending on the therapeutic strategy.
CONCLUSION: The results expand the current view on central mechanisms of
posttraumatic axon regeneration on the model of traumatic brachial plexopathy and
establish a neuromodulative effect of neuromidin and noofen. Some morphometric
parameters may be used as the markers of reactive neuroplastic processes in the
central nervous system.
PMID- 28514331
TI - [Diagnosis and treatment of migraine: Recommendations of the Russian experts].
AB - These recommendations on the diagnosis and treatment of migraine were elaborated
by Russian headache experts in accordance with the evidence-based practice.
Together with the latest classification, diagnostic principles and criteria of
different clinical sub-forms the consensus contains basic data on migraine
epidemiology, pathophysiological mechanisms, differential diagnosis and most
effective and evidence based approaches to pharmacological and non
pharmacological management of migraine patients.
PMID- 28514332
TI - [Clinical significance of nausea in migraine].
AB - AIM: To study the prevalence and intensity of nausea in pain, prodromal and
postdromal phases of migraine paroxysm, and in between the paroxysms in migraine
patients, depending on the type of migraine paroxysm and frequency of pain days,
and to evaluate an effect of nausea on the course of migraine. MATERIAL AND
METHODS: One hundred and four patients with migraine, aged from 18 to 60 years,
were examined. The intensity of nausea was evaluated by a 5-point verbal analogue
scale, and its intensity in between the paroxysms by the Gastrointestinal Symptom
Rating Scale. All of the patients underwent a complex examination of the
gastrointestinal tract. RESULTS AND CONCLUSION: Paroxysms with accompanying
nausea were found in 90% patients. Acute nausea was associated with older age,
earlier onset and longer experience of migraine. In a group of patients with
acute nausea, the frequency and intensity of migraine paroxysms, probability of
reoccuring pain in the first day and the severity of social disability were
higher. Development of nausea in between the paroxysms and its intensity was
significantly higher in patients with high intensity of nausea in migraine
paroxysms. Nausea in the prodrome was significantly associated with migraine
without aura and chronicity of the disorder. Patients with nausea in the prodrome
also had a longer painful phase and more severe social disability. No
relationship between organic diseases of the digestive tract and nausea was
found. Nausea can have its own pathological mechanisms not related to concomitant
diseases of the digestive tract that should be taken into account in therapeutic
interventions aimed at improving quality of life of the patients.
PMID- 28514333
TI - [Diagnosis of refractory forms of chronic primary headache].
AB - A number of patients with primary headaches remain insensitive or refractory to
treatment despite correctly selected drugs, adequate therapeutic dose and
duration of therapy. The importance of refractory problem is determined by the
fact that patients are completely maladjusted, disabled, and keeping these
patients is very difficult even for seasoned professionals. Determination of the
correct tactics and success of the treatment depends, in the first place, on the
correct diagnosis. This article discusses the diagnostic criteria for the most
important forms such as refractory chronic migraine or refractory chronic cluster
headache presented by experts of the European Headache Federation in two separate
Consensus.
PMID- 28514334
TI - [Anxiety and depressive disorders in Parkinson's disease].
AB - This review presents the most recent data of worldwide research on anxiety and
depressive disorders in patients with Parkinson's disease. Their characteristics
and epidemiology, pathogenetic and clinical features, methods of diagnosis and
treatment are presented. Depression occurs in 40-50% of patients with PD, anxiety
in 17-43% of patients. Pramipexole, a dopamine agonist, is only one drug
recommended for depression treatment. Nortriptyline and desipramine, belonging to
the group of tricyclic antidepressants (TCAs), are considered to be possibly
effective. There are no clear recommendations for treatment of anxiety. In
general, methods of therapy of anxiety and depressive disorders in PD are not
well understood which determines the conduct of large-scale studies in the
future.
PMID- 28514335
TI - [The quality of medical care and cooperation of patients with amyotrophic lateral
sclerosis in the Russian Federation].
AB - The quality of medical care for patients with amyotrophic lateral sclerosis (ALS)
in the Russian Federation is analyzed taking into account the cooperation of
patients. Two hundred and fifty-one patients with ALS were observed. Ninety-nine
patients, including 16 who were followed up, were examined. Other patients
(n=152) were consulted indirectly including 28 followed up. It has been shown
that 79,8% of the patients are characterized by the low level of cooperation with
neurologists regardless of the quality of medical care; 8.3% of patients are
managed in facilities (or by physicians), which don't use the International
standard of ALS management. Only 11.9% of patients receive medical care in
accordance with this standard and in these cases, the high level of cooperation
of the patients with medical services was recorded. A dual system that combines
the services provided by medical insurance, private treatment facilities, charity
organizations, structures of medical/social care with different levels of
availability and methods of consumer-provider interactions is the most effective.
PMID- 28514336
TI - [The quality of life in patients with a different types of myasthenia gravis].
AB - AIM: Researching quality of life in patients with myasthenia gravis at different
clinical variants of disease. MATERIAL AND METHODS: We studied 103 patients with
myasthenia gravis. A battery of tests and scales for assessment of neurological
deficit and quality of life was used. RESULTS AND CONCLUSION: Two types of
disease have been identified in myasthenia gravis: favorable and unfavorable. The
minimal duration of disease before thymectomy is the main determinant of the best
outcome. Favorable clinical type of myasthenia gravis was found in patients with
weakness in extraocular and limb muscles. Factors associated with a poor quality
of life included following: weakness in bulbar and respiratory muscles (p<0.003),
endocrine comorbidities (p<0.01) or thymoma (p<0.005).
PMID- 28514337
TI - [Sex differences in acute disturbances of cerebral blood circulation].
AB - It is shown that in the development of stroke observed sex differences, which
manifest themselves both clinically and by laboratory parameters. While men have
a higher incidence of stroke for most of his life, a woman in a more advanced age
have a higher risk for stroke. Sex differences in the development of stroke
depend on several factors, including genetic and hormonal changes throughout
life. Studies sex differences in the risk of stroke is only in the initial stage,
but the first results show that there are differences in neuronal cell death in
males and females after experimental ischemic stroke. A better understanding of
the mechanisms underlying the development of stroke in men and women will lead to
more appropriate treatment strategies for patients of both sexes.
PMID- 28514338
TI - [A comparative chemoreactome analysis of mexidol].
AB - AIM: To compare mexidol with control molecules (choline alfoscerate, piracetam,
glycine, semax) using chemoreactome analysis. MATERIAL AND METHODS: The chemical
structure of mexidol was compared to molecule metabolites extracted from the
Human Metabolome Database (HMDB) and a drug database. More than 40 000 of
metabolites from HMDB were used as a model of human metabolome. RESULTS AND
CONCLUSION: The chemoreactome analysis showed that mexidol may be (1) an agonist
of acetylcholine and GABA-A receptors; (2) an anti-inflammatory agent, the
effects of which are carried out by inhibiting the synthesis of pro-inflammatory
prostaglandins; (3) a neurotrophic agent with neuroprotective properties; (4) a
coagulation inhibitor; (5) a diabetes medication and (6) a hypolipidemic agent.
Compared to 'control' molecules, mexidol has a more pronounced safety profile (a
lower impact on serotonin, dopamine and adrenergic receptors, a lesser degree of
interaction with the potassium channels of the heart, MAO and P450 cytochromes).
The results of modeling allow to specify the mechanisms of action of mexidol at
the molecular level.
PMID- 28514339
TI - [Increased oral fluid remineraling function by endogenous and exogenous
saturation methods of its mineral complexes].
AB - RELEVANCE: One of the most common problems in modern caries prevention is the
development of techniques to increase tooth resistance to the effects of
cariogenic factors. Therefore, research is needed to study the chemical
composition of tissues like teeth and body fluids surrounding the tooth to
prevent demineralization process. The purpose of determining the effectiveness of
work- and correlation relationship between endo saturation exogenous methods oral
liquid mineral complexes. MATERIAL AND METHODS: In 95 patients analyzed the
chemical composition and structure of the oral fluid by IR spectroscopy. For the
collection of IR spectra used Verteh-70 spectrometer ('Bruker', Germany) and the
prefix of frustrated total internal reflection PLATINUM ATR diamond prism.
RESULTS AND DISCUSSION: A correlation between the use of endogenous and exogenous
methods of caries prevention, in favor of the former, as well as changes in the
mineral-organic and phosphate-carbon ratio in the dry residues of oral fluid.
PMID- 28514340
TI - [The impact of surgical and conservative treatment of periodontal disease on
structural and functional condition of major blood vessels].
AB - The study included 55 patients (24 men and 31 women aged 30-70 years) with
chronic periodontal disease and atherosclerosis of brachiocephalic arteries
(BCA). Patients in group 1 received only conservative treatment for periodontal
disease, while in group 2 both conservative and surgical treatment were
performed. The values were evaluated at baseline and 6 months after treatment.
Capillaroscopy and laser Doppler flowmetry showed an improvement in periodontal
regional vascular network. The level of IL-6 decreased by 3.7 pg/ml and 5.9
pg/ml, C-reactive protein - by 2.0 mg/l and 3.4 mg/l in groups 1 and 2
correspondingly. Dark-field microscopy showed the decrease in the thickness of
perfused boundary region by 0.05 mm and 0.28 mm, and the increase of red blood
cells filling by 1.2% and 7.8% correspondingly. According to the results of
ultrasound scanning of BCA after 6 months the number of atherosclerotic plaques
and lumen of the vessels in the area of the plaques has not changed. BCA tone has
not changed in group 1 and increased by 1-2% in group 2. Intima-media complex
thickness decreased in group 1 by 0.02-0.03 mm, in group 2 - by 0.04 mm. The
obtained data prove correlation of vascular status of periodontal and major blood
vessels.
PMID- 28514341
TI - [Endodontic treatment efficacy enhancement by means of instrumental
physiotherapy].
AB - The article describes in detail and examines the prospects of such methods as
electroodontodiagnosis, diathermocoagulation and apex-phoresis. It proves the
necessity of development and standardization of devices for the mentioned
treatment modalities that will improve the effectiveness an quality of caries
complications treatment.
PMID- 28514342
TI - [Evaluation of main and additional root canal curvature in maxillary molars].
AB - The aim of the study was to investigate the degree of the main and additional
root canal curvatures of the maxillary molars in Krasnoyarsk population. Main and
additional root canal curvature was measured in 48 maxillary first molars (M1)
and 122 second molars (M2) with cone beam computer tomography. In total 476
measurements were taken for M1 and 1038 for M2 (all measurements were doubled in
sagittal and coronal views). M2 showed more variety of root canal morphology and
significantly higher proportion of additional root canals. Curvature rates of M1
did not differ significantly from M2. Additional root canals had close or similar
curvature rates with the main ones. The obtained data are useful for the
improvement of root canal treatment efficacy and endodontic treatment planning.
PMID- 28514343
TI - [Effect of dexmedetomidine on perfusion of free flaps transferred to head and
neck].
AB - The paper presents the impact of perioperative care on feasibility of free fibula
flap transfer for facial reconstruction. Flaps vitality was measured by means of
somatic oximetry in 85 patients aged 20-74 years receiving reconstruction
procedures in midfacial and lower facial areas. The patients were divided in
three groups according to sedation agent used postoperatively. It has been
demonstrated that dexmedetomidine postoperative sedation significantly improved
free fibula flaps perfusion compared to propofol sedation.
PMID- 28514344
TI - [Erbium laser application for oral surgery in patients with platelet hemostatic
disorders].
AB - Hemostatic disorders are typically associated with prolonged bleeding after or
during surgical procedures. The aim of the study was to increase the efficiency
of oral surgery in these patients using erbium laser. Selected 46 patients
receiving oral surgery were randomly divided in 2 groups: 43 patients with
thrombocytopenia, trombocytemia and other platelet disorders treated with erbium
laser and a control group of 43 patients without concomitant pathology determined
for conventional surgical treatment. No postoperative bleeding was seen in group
1. Conventional procedures were associated with significantly more postoperative
pain and epithelization took 1-3 days longer. Erbium laser radiation is an up-to
date method which can be successfully used for oral surgery in patients with
hemostatic disorders.
PMID- 28514345
TI - [Immunohistochemical criteria for differential diagnostics of squamous epithelium
changes in pyogenic granuloma and squamous cell carcinoma of the oral mucosa].
AB - The paper presents an example of differential diagnostic studies for pyogenic
granuloma and oral squamous cell carcinoma (SCC). In the described case
immunohistochemistry with antibodies to Ki-67 and Gli1 was used as conventional
histological procedure proved to be inconvenient for adequate diagnostics. The
immunohistochemical study established increased proliferative activity of
epithelial cells specific both pyogenic granuloma and oral SCC, but intensive
Gli1 protein expression in membranes and cytoplasm of epithelial cells with
malignant transformation allowed differentiation of these neoplasms.
PMID- 28514346
TI - [Systemic toxicity of local anesthetics].
AB - The paper presents characteristics of local anesthetics used in dentistry and
maxillofacial surgery taking into account their effectiveness and toxicity. We
described the main clinical symptoms of manifestation of systemic toxicity and
measures for prevention of local anesthesia complications, as well as the
detailed protocol of 'lipid rescue' and resuscitation at manifestation of
systemic toxic reaction of local anesthetics with the mechanism of the fatty
emulsion action.
PMID- 28514347
TI - [Clinical and diagnostic rationale for the final stage of orthodontic treatment].
AB - The aim of the study was to improve the efficiency of the final stage of
orthodontic treatment. The study included 32 patients divided into two groups of
16. Orthodontic treatment was performed using a bracket system active self
ligation straight arc technique with step adjustment anthropometric quantitative
evaluation system (The ABO Model Grading System). Centric occlusion and centric
relation were analyzed at baseline and after treatment by mandible position
indicator MPI (Mandibular Position Indicator). The first group received treatment
according to conventional protocol, in the second group braces were readjusted by
indirect bonding after ABO anthropometric measurements. The efficiency of
orthodontic treatment using ABO system at the late stages of adjustment in the
second group was significantly higher than in the first group (p=0.002248;
p=0.023431, respectively). MPI analysis in the first group in 10 (62.5%) patients
showed mismatch of centric occlusion and centric relation not seen in the second
group. In 3 (18.75%) patients of group 2 the difference did not exceed 0.5 mm
which was considered normal. Thus, the application of ABO anthropometric system
followed by readjustment of incorrectly positioned brackets by indirect bonding
promotes MPI values improvement, which in turn allows getting the most accurate,
and stable results of orthodontic treatment.
PMID- 28514348
TI - [Dynamics of immunological features of oral liquid in children with chronic
catarrhal gingivitis living on polluted territories with fluoride and iodine
deficiency].
AB - The aim of the study was to assess the state of oral liquid (OL) immunity in
children with chronic catarrhal gingivitis (CCG) living in adverse environmental
conditions. 120 children aged 7-15 residing in ecologically unfavorable areas of
Lviv region were examined, while 75 children living in 'relatively clean' region
were involved in the control group. Chronic catarrhal gingivitis was diagnosed
according to Danilevskiy classification (1994). The level of cytokines in oral
liquid of 7-years-old children living in ecologically polluted region (EPR), was
(198.19+/-4.11).106/l, which was 1.4 times more than in the conditionally clean
region (CCR): (141.09+/-4.10).106/l (p<0.01). Analysis of cytokine profile in 7
years-old from EPR showed increased levels of IL-6 proinflammatory cytokines by
11.22% (13.78+/-0.38 pg/ml vs 12.39+/-0.50 pg/ml in controls, p<0.05) and the
decrease of IL-4 anti-inflammatory cytokine by 26.9% (7.12+/-0.62 pg/ml vs 9.74+/
0.58 pg/ml, p<0.01). In 12 years-old from EPR quantity of leukocytes in OL was
1.3 times higher than in controls ((246.81+/-4.16).106/l vs (190.02+/
4.11).106/l, p<0.01), the increase of the IL-6 content of 27.1% (p<0.01) and
reduce of the IL-4 of 21.5% (p<0.05) compared to controls was also seen. At the
age of 15 further increase of leucocytes in children from EPR was revealed:
(297.53+/-4.15).106/l, which was 1.2 times higher than in controls (p<0.01).
Changes of cytokine profile in this age group were characterized by increased
content of IL-6 of 26.41% (p<0.05) and IL-4 drop of 28.53% (p>0.05). Thus the age
dependent trend for the increase of leukocytes count in OL and pro-inflammatory
cytokine IL-6 with the decrease of anti-inflammatory cytokine IL-4 is noted in
children with CCG living in EPR.
PMID- 28514349
TI - [Elastic properties and porosity of dental blocks made from non-metal materials
used for chairside CAD/CAM crowns].
AB - Elastic properties and internal structure of glass-ceramic, feldspatic ceramic,
PMMA and hybrid blocks for chairside CAD/CAM dental crowns were assessed by
pulsed acoustic microscopy. Elastic modulus of hybrid ceramic was 1.5 times
inferior to feldspatic ceramic and glass-ceramic but almost 10 times higher than
those of polymer samples. We found the presence of pores from a few to hundreds
of microns in the bulk of inorganic materials samples, isolated point defects
were revealed in polymer materials while in hybrid material defects were not
found.
PMID- 28514350
TI - [Improvement of training quality in continuous medial education of dentists and
maxillofacial surgeons].
AB - The new concept of continuous medical education is based on individual learning
paths of each specialist in conjunction with the use of modern educational
technologies, including IT. The aim of this study was to undertake a review of
modern methods of health care professionals training in the framework of
continuous medical education profile introduced by the Ministry of Health. The
paper presents the best IT practices of Central Research Institute of Dentistry
and Maxillofacial Surgery in the training of dentists and maxillofacial surgeons
aimed for the modernization of medical education.
PMID- 28514351
TI - [Essential questions of training of dentists for accreditation].
AB - The paper presents sociological study aimed to analyze the conditions and
methodological rationale for the basic directions of optimization of
accreditation procedure for dentists. The study included 129 graduates of dental
faculties of educational institutions of Sechenov First Moscow State Medical
University. The material was collected by questionnaire survey and interviewing.
The obtained results show that the introduced system of professionals'
accreditation is an innovative educational technology allowing objectively assess
the level of theoretical and practical training of dentists. Much of its
effectiveness depends on the quality of produced and updated on a timely basis
uniform base of assessment tools, the selection of the most prepared members for
the accreditation commissions and creation of adequate conditions for its
implementation in educational and scientific organizations.
PMID- 28514352
TI - [Synthetic osteoplastic materials for alveolar bone augmentation before dental
implantation].
AB - The study presents scientific data about surgical preparation of the alveolar
bone before dental implantation by applying synthetic osteoplastic materials. The
review analyzed the results of experimental and clinical studies on structural
features and the efficiency of these materials, the time for replacement of new
formed bone tissue and contains comparative analysis of the efficiency of
synthetic bone substitutes and other types of osteoplastic materials.
PMID- 28514353
TI - [Mantle dentin as biomodel of materials for structural teeth restoration].
AB - The article describes a structural element of natural teeth - mantle dentin. It
has been shown that the presence of this element in the structure of a natural
tooth largely ensures its strength under the influence of repeated loads in a
functional oral environment and arrests crack growth at the enamel/dentine
interface. This later effect is explained by the influence of a thin layer of
mantle dentine, which has physical and mechanical characteristics different from
that of the main dentin.
PMID- 28514354
TI - [Out-patient dental care in patients with arterial hypertension].
AB - The aim of the study was to improve dental treatment quality in patients with
arterial hypertension. The study included 256 patients with arterial hypertension
(153 females, 103 males) aged 35 to 60 years. Anesthesia efficacy was assessed by
visual analog scale after treatment. Oral adverse effects caused by regular
intake of antihypertensive drugs and interrelation with articaine and mepivacaine
were described. The study proved high efficacy of 4% articaine 1:200 000. The
efficacy of 3% mepivacaine with no vasoconstriction agents was 86.4+/-2.3% but
may be enhanced to 93.3+/-2.3% by preventive non-steroid anti-inflammatory agents
taken 25-30 minutes before treatment in maximal daily dosage.
PMID- 28514355
TI - [The prevalence of tympanosclerosis and the effectiveness of its surgical
treatment].
AB - The objective of the present study was to characterize the epidemiological
variants of tympanosclerosis and the effectiveness of the surgical treatment of
the patients presenting with this condition. We have undertaken the analysis of
the results of 1965 surgical interventions on the patients suffering from
different forms of chronic otitis media (COM) performed during the period from
2009 till 2014 with a view to determining the frequency of tympanosclerosis
(TSC). In 542 cases, it proved possible to evaluate the intraoperative findings,
stages and methods of reconstructive surgery, the anatomical and functional
outcomes and effectiveness of the intervention. At present, the signs of
tympanosclerosis are identified in 27.6% of the patients presenting with chronic
otitis media including 88.7% and 11.3% suffering from the perforating and non
perforating forms of this pathology, respectively. In 74% of the cases its
manifestations are diagnosed in the patients having the tubotympanic form of COM.
In 53.3% of the patients TSC foci are responsible for the fixation of the
ossicular chain whereas in 46.7% of the cases the auditory ossicles retain
mobility. As many as 88.6% of the patients underwent the one-step surgical
intervention, 10.7% were managed using two-step surgery, and 0.7% of the patients
were given the three-stage treatment. Type I tympanoplasty was performed in 62%
of the patients, type III tympanoplasty in 30.4%, and various types of
stapedoplasty in 4.6% of the cases. The favourable anatomical and functional
outcomes at the first stage of the surgical intervention with the use of the
autogenous tissues for tympano- and ossiculoplastic surgery were achieved in
87.9% of the patients on the average (by means of the closure of the tympanic
defect in 92.2% and by re-fixation of the selected elements of the ossicular
chain in 17.3%of the cases). The anatomical and functional effectiveness of the
second-stage surgical intervention was estimated at 93.1%.
PMID- 28514356
TI - [The criteria for the relationship between hearing impairment and professional
occupation and the criteria for professional suitability in terms of hearing
among the aeronautical personnel engaged in civilian aviation].
AB - This article describes the main clinical features associated with the development
and manifestations of disturbed sound perception in the members of the
aeronautical personnel engaged in the Russian civilian aviation. The main expert
criteria for the relationship between the diseases of the organs of hearing (as
exemplified by chronic sensorineural hearing impairment) and professional
occupation have been developed based on the results of the clinical and
diagnostic examination with the use of whispered and loud speech acumetry, tonal
threshold audiometry, speech audiometry, impedancometry and evoked optoacoustic
emission. Civilian aviation sectoral approaches to the evaluation of professional
suitability in terms of hearing among the aeronautical personnel are considered
in accordance with the criteria adopted by the International Civil Aviation
Organization (ICAO), a specialized UN agency that sets the international
standards for the civilian aviation and co-ordinates its development with the
purpose of enhancing the safety and effectiveness of flights. The criteria are
formulated for the solution of the expert problems arising from the relationship
between the professional occupation and the diseases of the organs of hearing and
for the evaluation of the professional suitability in terms of hearing among the
aeronautical personnel engaged in civilian aviation.
PMID- 28514357
TI - [The results of universal audiological screening of newborn infants in the
Astrakhan region].
AB - We have evaluated the results of universal audiological screening of 93 352
newborn infants performed in the Astrakhan region of the Russian Federation
during the period from 2009 till 2015. The screening coverage amounted to 95%.
The prevalence of hearing disorders was estimated at 1:1111 and that of their
severe forms at 1:3000. The clinical significance of the examination during its
first stage consists of the exclusion of evoked otoacoustic emission. After the
completion of the second stage, it is necessary to carry out the regular medical
follow up observation of the children suffering from hearing impairment and to
undertake the early rehabilitative treatment based on the application of hearing
aids and prosthetic devices. Sensorineural hearing loss was found to be the
predominant form of hearing disorders in the children during the first year of
life (80%). The impairment of hearing was documented in 22.3% of the premature
children which suggests the necessity of long-term monitoring of evoked
otoacoustic emission in these patients.
PMID- 28514358
TI - [Ionizing radiation and laryngeal cancer].
AB - The cause behind the currently ever increasing number of patients presenting with
laryngeal cancer lies not only in the lack of the apprehensive attitude toward
oncological diseases among the medical profession but also in the changing
conditions of human life and environment. As many as 165 patients suffering from
laryngeal cancer of the 490 ones admitted to our clinic had undergone the
influence of ionizing radiation before they were allocated to the main study
group while the remaining 325 cases made up the control group. The former group
included 112 firefighters of the Chernobyl disaster. It was shown that the
progression rate of the disease among the patients of the main group was much
higher than among those comprising the control one. A similar difference was
documented in the occurrence of regional and remote metastases that were not
infrequently the earliest manifestations of the disease. All the patients of the
main study group were given the surgical treatment. The firefighters died within
one year after the onset of the treatment due to multifocal tumours, regional and
remote metastases.
PMID- 28514359
TI - [The mathematical approaches to differential diagnostics of acute pharyngeal
diseases].
AB - The objective of the present study was to elaborate the program for differential
diagnostics of acute pharyngeal diseases based on the 'ENT-Neuro' artificial
neuronal network. The study group was formed by means of sampling patients with
acute pharyngeal diseases from a set of case histories of the subjects presenting
with acute inflammatory diseases. The data thus obtained were employed to develop
the expert system to support the decision making process with the use of the 'ENT
Neuro' artificial neuronal network that allows to carry out diagnostics of
various inflammatory diseases of the pharynx including the following nosological
entities: paratonsillitis, parapharyngitis, acute tonsillitis, and acute
pharyngitis, with the minimal probability of erroneous diagnosis (4%). The
proposed expert system makes it possible to choose the optimal treatment strategy
for the management of various pharyngeal diseases taking into consideration the
severity of a concrete pathology and thereby to reduce to a minimum the risk of
the related complications.
PMID- 28514360
TI - [Preoperative MRI diagnostics of the topographic features of neck arteries in the
patients presenting with chronic tonsillitis].
AB - The objective of the present study was to determine the frequency of
abnormalities of the major neck vessels and elucidate the specific features of
blood supply of palatine tonsil based on the results of MRI performed in the
vasculature-targeting regimen. A total of 109 patients presenting with chronic
tonsillitis (including 64 women and 45 men at the age varying from 15 to 54
years) were available for the examination. All the patients underwent the MRI
diagnostic study of the neck vessels by way of the preliminary evaluation of
their condition at the pre-hospital stage. Abnormalities in the internal carotid
artery were documented in 11.9% of the cases (including C- and S-shaped
tortuosity of internal carotid artery in 6.88%, kinking and coiling of internal
carotid artery in 4.13% and 0.92% of the patients, respectively). The majority of
the detected abnormalities were located above the upper pole of the palatine
tonsil which allowed to avoid the risk of the injury to the main neck vessels and
prevented possible hemorrhage. One patient (0.46%) presented with kinking of the
right internal carotid artery located in the immediate proximity to the capsule
of the palatine tonsil close to its mid-third portion. There was no evidence that
the present study gave rise to any malformation of the internal carotid artery
and internal jugular vein. The proposed diagnostic method makes it possible to
detect a rare anatomical feature of the development of the internal carotid
artery discovered in a single patient (0.04%) out of the 2398 operated ones. This
finding is of clinical significance and needs to be borne in mind when preparing
the planned surgical intervention for the treatment of chronic tonsillitis. The
results of the present study should be taken into consideration when prescribing
the surgical treatment to the patients suffering not only from chronic
tonsillitis but also from other ENT diseases, in the first place pharyngotympanic
tube pathology.
PMID- 28514361
TI - [The complications of transethmoidal decompressive orbitotomy associated with
endocrine ophthalmopathy].
AB - The objective of the present study was the analysis of the results of
transethmoidal decompressive orbitotomy (TEDO) with the resection of the bone
matrix of the medial and inferior orbital walls in the patients presenting with
endocrine ophthalmopathy (EOP) with the purpose of reduction of the risk of
development of this pathological conditions. A total of 51 patient with EOP at
the stage of complete remission or pharmacotherapeutic compensation underwent
transethmoidal decompressive medial orbitotomy in the ENT Clinic of 1 I.M.
Sechenov First Moscow State Medical University during the period from 2006 to
2016. Twenty two of these patients presented with the unilateral process and 29
ones with bilateral exophthalmos. The surgical intervention was performed on the
total of 80 eye orbits. The main complaints of the treated patients during the
post-operative period included difficulties in nasal breathing (33%), dryness of
the nose and crust formation (43%), discharge from the nose and along the
posterior pharyngeal wall (15%), nasal bleeding (2%), pain in the forehead and
maxillary region (8%), headache (2%). As far as the state of eyes and sight is
concerned, 14 (27%) patients reported double vision at the primary gaze position
while 6 others (12%) complained of the appearance of diplopia upon a change in
the gaze position during the post-operative period. The post-operative endoscopic
study revealed synechiae of different localization in the nasal cavity (47%),
discharge from the maxillary sinuses (16%) and from the frontal sinus (2%). Eight
(16%) patients were found to suffer from maxillary sinusitis, one had acute
frontitis, and one sphenoidal sinus mucocelle. These complications were
eliminated by pharmacotherapy and additional surgical interventions (2%).
Analysis of the results of the study has demonstrated that the above
complications were associated with the inadequate post-operative care for the
nasal cavity, the excessively large size of the bone window formed during
transethmoidal decompressive orbitotomy, resection of the inferior orbital wall,
intrusion of the medial rectus muscle of the eye into the wide bone window. We
evaluated the possible influence of the orbital soft tissues on the physiological
parameters of the functioning of the paranasal sinuses in the post-operative
period including blockade of the paranasal drainage pathways by the prolapsed
orbital tissues. A few possible approaches to the reduction of the risk of post
operative complications are proposed. The authors emphasize the importance of the
further improvement of the surgical treatment of endocrine ophthalmopathy.
PMID- 28514362
TI - [The laryngeal condition in the patients presenting with euthyroid multinodular
goiter as evaluated by direct laryngoscopy].
AB - The objective of the present study was to improve diagnostics of disturbances in
the laryngeal condition of the patients presenting with euthyroid multinodular
goiter with special reference to the condition of the upper respiratory passages.
The preoperative characteristic of 398 patients included the description of the
predominant clinical syndrome (the neoplastic and compressive variants) and
specification of the morphological type of the disease to promote the decrease of
operative activity with respect to colloidal proliferative goiter. Direct
laryngoscopy was employed in addition to the traditional diagnostic techniques
during both the surgical operation and the follow-up observation. Hoarseness
developed in the postoperative period in 13.4% to 16.9% of the patients.
Postoperative transient and persistent laryngeal paresis was documented in 1.5%
and from 1.5% to 4.2% of the cases respectively. Direct laryngoscopy revealed the
symptoms of laryngitis and laryngotracheitis as well as foci of leukoplakia,
laryngeal cysts and nodules, besides disturbances in the mobility of the vocal
chordae. It is concluded that the above pathological changes in the laryngeal
structures should be identified during the preoperative examination of the
patients presenting with euthyroid multinodular goiter while direct laryngoscopy
must be included in the program of postoperative supervision.
PMID- 28514363
TI - [The immunological characteristics and enzymatic activity of lymphocytes from the
peripheral blood of the children presenting with pharyngeal tonsillar
hypertrophy].
AB - The objective of the present work was to study the immunological characteristics
and activity of NAD(P)-dependent dehydrogenases in peripheral blood lymphocytes
in the young children presenting with pharyngeal tonsil hypertrophy (PTH). A
total of 57 children at the age from 1 to 3 years with PTH were available for the
examination. The control group was comprised of 35 age-matched practically
healthy children. The amount of CD3+, CD4+, CD8+, CD16+/56-, and CD19+ cells in
the peripheral blood was determined with the use of the cytoflowmetric technique.
The activity of NAD(P)-dependent dehydrogenases in the peripheral blood
lymphocytes was quantified by the method of A.A. Savchenko and co-workers ([14].
Serum IgA, IgM, and IgG levels were measured as described by G. Mancini and co
workers [12], and the levels of the circulating immune complexes (CIC) by the
method of Haskova and co-workers [13]. The children presenting with pharyngeal
tonsil hypertrophy were found to undergo changes in the immune-phenotypic
spectrum of peripheral bloods lymphocytes, the decrease of serum IgA
concentration, and the increase in the serum CIC level. The activity of riboso-5
phpsphate- and NADH-dependent reactions of the macromolecular synthesis was
increased whereas the role of the malate-aspartate shunt in the cellular energy
metabolism and activity of glycolysis decreased. On the contrary, the substrate
flow in the tricarbonic acid cycle was rather high while glutathione reductase
activity was low. The present study has shown that the children presenting with
pharyngeal tonsil hypertrophy underwent changes in the immune and phenotypic
spectrum of peripheral bloods lymphocytes, the decrease of serum IgA
concentration, and the increase in the serum CIC level.
PMID- 28514364
TI - [Radiodiagnostics of odontogenic maxillary sinusitis].
AB - The objective of the present study was to analyze the potential of such
techniques as X-ray, multi-slice computed tomography (MSCT), and cone-beam
computed tomography (CBCT) for diagnostics of odontogenic maxillary sinusitis.
The secondary objective was to describe changes in maxillary sinuses identifiable
with the help of the above methods. The study included 166 patients at the age
varying from 21 to 81 years presenting with odontogenic maxillary sinusitis. All
of them underwent the roentgenological examination. The study has demonstrated
the low effectiveness of the projection radiography techniques. The use of
computed tomography made it possible to verify the diagnosis in 110 (66.2%) of
the 166 examined patients, to reveal the radiological characteristics of the
deyected changes suggesting their odontogenic etiology, and to choose the proper
strategy for the further treatment. It is concluded that MSCT and CBCT are the
most informative methods to be used for diagnostics of odontogenic maxillary
sinusitis.
PMID- 28514365
TI - [The detection of the human papilloma virus during hyperplastic processes in the
nose, ears and throat].
AB - The objective of the present work was to carry out the virological and
histological studies of various neoplastic and hyperplastic processes in the
nose, ears, and throat with a view to identifying the presence of human papilloma
virus and Epstein-Barr virus. The brush biopsies and remote neoplasms obtained
from 18 patients (including 2 children and 16 adults) presenting with various ENT
diseases and tumours were available for the virological investigation with the
use of the polymerase chain reaction (PCR) and a system MY09-MY11 degenerate
primers . The histological study of biopsies and remote neoplasms was carried out
by means of conventional light microscopy. The virological and histological
studies conducted in parallel confirmed the diagnostic significance of
morphological changes at the tissue and cellular levels caused by the human
papilloma virus.
PMID- 28514366
TI - [Applicability of antibacterial agents in chronic tonsillitis treatment].
AB - The purpose of the present study was to evaluate the effectiveness of
nitrofuranes applied for the treatment of chronic tonsillitis. A total of 92
subjects divided into three cohorts were involved in this study. Cohort 1
included 43 patients presenting with decompensated chronic tonsillitis and having
pathogens in palatine tonsil lacunae. Cohort 2 was comprised of 13 patients with
compensated chronic tonsillitis having pathogenic microflora of the same
localization, while Cohort 3 was composed of 36 patients resembling those of
cohort 1 in terms of clinical presentation, pathogen composition, and microbial
spectrum. While the patients of cohort 1 and cohort 2 were treated by rinsing
their tonsil lacunae with a furasol solution as a single-drug therapeutic
procedure, those comprising Cohort 3 underwent treatment with furacilinum for the
same purpose. The results of the study give evidence of the important advantages
of furasol therapy over other modalities for the conservative treatment of
chronic tonsillitis.
PMID- 28514367
TI - [The new possibilities for the treatment of chronic cough associated with
postnasal drip].
AB - Cough is considered to be one of the leading clinical symptoms associated with
the pathological changes in the respiratory system. Notwithstanding a great
variety of therapeutic pharmaceutical products possessed of the antitussive
action, physicians tend the give preference to the preparations producing the
combined effect. The present article reports the results of the clinical study
designed to evaluate the effectiveness and safety of the application of rengalin
exhibiting the combined antitussive, anti-inflammatory, and broncholytic action
in the patients presenting with the postnasal drip syndrome. The comparison of
the therapeutic effects of rengalin with those of other therapeutic modalities
frequently employed for the management of postnasal drip give evidence of the
high efficiency of this product for the optimization of the treatment of this
condition and the associated chronic cough.
PMID- 28514368
TI - [The use of modern topical medications for the stepwise treatment of allergic
rhinitis: the effectiveness and prospects for the further extension of their
application].
AB - The objective of the present work was to summarize the results of clinical
studies designed to evaluate the effectiveness of 'Momate Rhino Advance' in the
form of the nasal spray (based on the fixed combination of mometasone furoate and
azelastine) that finds an increasingly wide application for the treatment of
allergic rhinitis. The available data give evidence that this medication can be
prescribed to the patients presenting with the severe and moderate form of
allergic rhinitis. The treatment should be started with the use of the combined
preparation and continued, after the adequate control of the clinical symptoms of
allergic rhinitis is achieved, using 'Momate Rhino' during the next 2-4 weeks for
the reliable management of the disease. It is concluded that the proposed
strategy makes it possible to avoid the simultaneous application of multiple
medications (polypragmasy) and thereby reduce the intake of medicines by the
patients suffering from allergic rhinitis.
PMID- 28514369
TI - [The role of topical glucocorticoids in the treatment of rhinosinusitis].
AB - The guidelines of the European position paper on rhinosinusitis and nasal polyps
(EPOS, 2012) ascribe the highest strength and the most comprehensive evidence
based significance to the application of intranasal glucocorticosteroids (inGCS)
as the first-line therapy for the patients presenting with acute and polypous
rhinosinusitis; moreover they are recommended as the medications of choice for
the treatment of chronic rhinosinusitis in the absence of polyps. The author
presents the data concerning the mechanism of action, clinical effectiveness, and
safety of inGCS used for the treatment of acute, recurrent, and chronic
rhinosinusitis. It is shown that mometason furoate produces the favourable
therapeutic effect and is possessed of beneficial pharmacodynamic and
pharmacokinetic properties in the cases of its topical application. The
comparative randomized clinical study (RCS) of the new preparation of mometason
furoate in the form of the intranasal spray (manufactured by 'Teva' Ltd.)
registered in the Russian Federation in 2015 has demonstrated that it can be
considered as a therapeutic equivalent to nasonex.
PMID- 28514370
TI - [Acute otitis media in a 5 year-old child complicated by mastoiditis and abscess
of the temporomandibular joint].
AB - This article was designed to report a case of otogenic abscess of the
temporomandibular joint in a 5 year-old child. The specific feature of this
observation is a rare complication of acute otitis media (otogenic abscess of the
temporomandibular joint). Of crucial importance for the establishment of the
correct diagnosis was the timely evaluation of the state of the temporomandibular
bones by means of CT examination.
PMID- 28514371
TI - [IgG4-related sclerosing disease of the larynx].
AB - IgG4-related sclerosing disease of the larynx (IgG4-SD) is a recently described
immunodependent systemic pathology characterized by diffusive or focal
inflammatory infiltration of the affected organs and tissues by plasma cells
expressing IgG4; it is accompanied by the subsequent development of obliterative
phlebitis and fibrosclerosis associated with the increase of the serum IgG4
level. According to the recently published materials, the disease can also
develop in the respiratory system. The present article describes the first
documented case of IgG4-related sclerosing disease with the isolated lesion of
the larynx. The diagnosis was established based on the results of the
comprehensive examination that made it possible to exclude systemic lesions, to
determine the IgG4 level in the serum, and to carry out the immunohistochemical
study of the histological preparations stained for the detection of IgG4
releasing plasmocytes. After verification of the diagnosis, the patient underwent
a course of systemic hormonal therapy that resulted in the stable clinical and
roentgenological remission of the disease that persists up to the present time.
PMID- 28514372
TI - [Secondary closed rhinoplasty in the patient presenting with post-injurious
deformation of the external nose].
AB - The authors describe the process of the surgical treatment of a patient
presenting with the displaced fracture of the nasal bones involving the left
orbital wall. The correction was performed by means of secondary closed
rhinoseptoplastic surgery. The special emphasis is laid on the importance of
computer-assisted modeling for the planning and achievement of the favourable
surgical outcome.
PMID- 28514373
TI - [Acute otitis media in the children: etiology and the problems of antibacterial
therapy].
AB - The objective of the present review was to summarize the currently available
literature data on etiology of acute otitis media in the children, the role of
biofilms in the development of this pathology, and sensitivity of its principal
causative factors to various antibiotic medications. The secondary objective was
to elaborate the practical guidelines for the prevention of acute otitis media in
the children.
PMID- 28514374
TI - [The role of the vomeronasal system in the formation of the human sexual
behaviour].
AB - This review deals with the structure and function of the vomeronasal system and
evaluation of its influence on the sexual sphere of humans and animals. Special
attention is given to the role of pheromones in the regulation of the sexual
behaviour. The data concerning the function of the vomeronasal organ following
surgical interventions in the nasal cavity are discussed.
PMID- 28514376
TI - [Ray diagnostics and surgical tactics for chronic pancreatitis].
PMID- 28514375
TI - [The etiopathogenetic aspects of idiopathic sensorineural impairment of hearing].
AB - The objectives of the present work were the overview of the results of the modern
investigations concerning etiology of idiopathic sensorineural impairment of
hearing as well as the analysis of the theory of microthrombus formation and its
role in pathogenesis of hearing impairment.
PMID- 28514377
TI - [Iliac arteries and aortic repair in patients with retroperitoneal sarcoma].
AB - AIM: To evaluate the results of surgical treatment in patients with
retroperitoneal sarcoma and invasion into great vessels. MATERIAL AND METHODS:
For the period 2009-2016 fourteenth patients with retroperitoneal sarcoma
underwent resection and repair of great vessels at the abdominal department of
N.N. Blokhin Russian Cancer Research Center. In 12 cases circular resection of
infrarenal aorta, aortic bifurcation and iliac arteries followed by their
replacement was made. 2 patients underwent circular resection of iliac arteries.
RESULTS: Postoperative morbidity was 42.8%. There was no postoperative mortality.
10 of 14 patients are alive from 2 to 70 months after surgery. One patient died
in 2 months postoperatively from unknown reasons, 3 patients died in 18, 20 and
30 months respectively due to progression of the disease. CONCLUSION: Overall
survival and acceptable surgical risk underline the value of en block resection
of retroperitoneal sarcoma together with involvement blood vessels.
PMID- 28514378
TI - [Comparative analysis of static scintigraphy and computerized tomography in
assessment of remnant liver volume after advanced hepatic resection].
AB - AIM: To perform a comparative analysis of computerized tomographic volumetry and
scintigraphic liver volumetry in assessment of remnant liver volume after
advanced hepatic resection. MATERIAL AND METHODS: Static hepatobiliary
scintigraphy and CT volumetry were performed in 45 patients with various liver
tumors who underwent advanced hepatectomies (more than three segments). RESULTS:
There were no any significant differences in volumetric parameters obtained by CT
and scintigraphic volumetry. CONCLUSION: Scintigraphic volumetry data are similar
to those of CT volumetry in evaluation of future remnant liver volume.
Scintigraphic volumetry may be used as an alternative in assessment of future
remnant liver volume after advanced hepatic resections.
PMID- 28514379
TI - [Closed management of pancreatic necrosis complicated by diffuse peritonitis].
AB - AIM: To assess an efficiency of closed management of pancreatic necrosis
complicated by widespread peritonitis by using of elective laparoscopic sanations
with ultrasonic processing of an abdominal cavity and retroperitoneal space.
MATERIAL AND METHODS: Treatment of 111 patients with pancreatic necrosis
complicated by diffuse peritonitis was analyzed. Closed management was used in 41
patients (main group). Among them there were 12 patients who underwent
laparoscopic sanation with ultrasonic cavitation of abdominal cavity,
laparoscopic drainage of omental bag, US-assisted puncture drainage of
retroperitoneal space and 29 patients after laparotomy followed by laparoscopic
lavage and low-frequency ultrasound through retroperitoneal drains which were
deployed during lumbotomy or under US control. Control group included 70 patients
in whom open treatment of diffuse peritonitis was used (laparotomy, lumbotomy,
omentobursostomy). Monitoring of hepatonephric dysfunction, endogenic
intoxication was carried out. RESULTS: It was concluded that developed technique
is associated with better clinical and laboratory data due to less surgical
trauma and ultrasonic cavitation in early postoperative period. Rapid recovery of
liver function, decrease of endogenic intoxication and mortality rate were
observed. So, this method may be recommended for patients with pancreatic
necrosis complicated by diffuse peritonitis.
PMID- 28514380
TI - [Transcatheter embolization in prevention of recurrent bleeding from stomach
ulcers].
AB - AIM: To evaluate an efficacy of endovascular hemostasis in patients with gastric
ulcerative bleeding and high risk of recurrent bleeding and death. MATERIAL AND
METHODS: The work is based on a study of the results in 30 patients with gastric
ulcerative bleeding, high risk of recurrent bleeding (rebleeding forecast system
(RFS) score over 17) and high risk of death (SAPS II score over 30). We attempted
transcatheter embolization of left gastric artery to prevent rebleeding. The
control group consisted of 60 patients with gastric ulcerative bleeding and the
same RFS and SAPS II values in whom angiography and endovascular hemostasis were
not performed. RESULTS: Technical success of endovascular hemostasis was achieved
in 25 (83.3%) cases. In 5 cases embolization was not performed. Complications
after transcatheter angiography and embolization were absent. Recurrent bleeding
after technically successful embolization was observed in 3 (12.0%) patients. In
all cases PVA microemboli were used. Mortality was 11.1% (3 patients).
CONCLUSION: Endovascular hemostasis in patients with severe comorbidities (SAPS
II score over 30) and high risk of rebleeding (RFS score over 17) reduced
incidence of recurrent bleeding from 36.7% to 11.1%.
PMID- 28514381
TI - [Complications and long-term results of delayed esophagoezophagostomy for
esophageal atresia].
AB - AIM: To evaluate complications and long-term results of delayed
esophagoesophagostomy in children with esophageal atresia (EA). MATERIAL AND
METHODS: 165 EA children were operated at the Filatov Municipal Children's
Hospital #13 for the period 2006-2016. Primary esophageal anastomosis was
performed in 136 (82.4%) children with tracheoesophageal fistula. In 5 (3%)
neonates with non-fistulous EA esophago- and gastrostomy were made for further
coloesophagoplasty. Other 24 (14.5%) children underwent gastrostomy for delayed
esophagoesophagostomy. 6 (25%) of them died within 12 days after admission. 18
survivors with gastrostomy subsequently underwent delayed esophagoesophagostomy.
RESULTS: Postoperative complications occurred in 16 (88.9%) children. Esophageal
anastomosis failure occurred in 4 (22.2%) patients, stenosis of anastomosis in 11
(61.1%) children, gastroesophageal reflux in 14 (77.8%) children. Early
postoperative mortality was 16.7% (3 children). In remote period 92.3% of
children were not adapted to normal diet and only in 7.7% of patients eating
behavior corresponds to the age. 11 children underwent prolonged esophageal
bougienage. 9 children underwent re-operation after delayed anastomosis.
Esophageal extirpation was made in 4 children. CONCLUSION: Esophago- and
gastrostomy provides 100% survival if primary esophageal anastomosis is
impossible. Herewith, in children without esophagostomy mortality rate was 25%.
We still can not confirm that delayed esophageal anastomosis is a good
alternative for children with esophageal atresia. In view of our results the
number of candidates for delayed esophageal anastomosis should be reduced.
PMID- 28514382
TI - [Laser technologies in treatment of posttraumatic rectal fistulas].
AB - AIM: To assess the results of surgical treatment of posttraumatic rectal fistulas
using current laser technology. MATERIAL AND METHODS: Surgical treatment of 134
(10.9%) patients with posttraumatic rectal fistulas was analyzed. The control
group of conventional treatment included 58 (43.3+/-3.4%) patients, the main
group - 76 (56.7+/-3.4%) patients. In the main group we used carbon dioxide laser
device 'Lancet-2' (Russia) with a wavelength of 10.6 microns, capacity up to 20
W, and contact laser device 'Atkus-15' (Russia) with a wavelength of 0.81 microns
and output power up to 15W. In postoperative period all patients underwent daily
infrared laser irradiation of wound surface with an exposure of 5-10 min,
wavelength of 0.635+/-0.005 microns, output power 25 mW ('UZOR-3 KS' (Russia,
Kaluga)). RESULTS: The complex surgical treatment with modern laser technologies
have reduced the incidence of complications from 19.0+/-5.1% to 7.9+/-3.1%
(OR=0.37; 95% CI; 0.13-1.06, p<0.05). The long-term results improved in 50.0+/
13.4% of the control group and in 77.8+/-6.9% of the main group (chi2=5.22;
p<0.05). CONCLUSION: Thus, laser technology has reduced twice the number of
postoperative complications and improved long-ter. RESULTS: 98.2% of patients
achieved medical and social rehabilitation in main group and 96.4% of patients in
control group.
PMID- 28514383
TI - [Efficiency of combined methods of hemorroid treatment using hal-rar and laser
destruction].
AB - AIM: To develop the combined method of treatment of hemorrhoids with arterial
ligation under Doppler control and laser destruction of internal and external
hemorrhoids. MATERIAL AND METHODS: The study included 100 patients with chronic
hemorrhoids stage II and III. Combined method of HAL-laser was used in study
group, HAL RAR-technique in control group 1 and closed hemorrhoidectomy with
linear stapler in control group 2. Somparative evaluation of results in both
groups was performed. RESULTS: Combined method overcomes the drawbacks of
traditional surgical treatment and limitations in external components elimination
which are inherent for HAL-RAR. Moreover, it has a higher efficiency in treating
of hemorrhoids stage II-III compared with HAL-RAR and is equally safe and well
tolerable for patients. This method does not increase the risk of recurrence,
reduces incidence of complications and time of disability.
PMID- 28514385
TI - [The effects of diosmin and hesperidin on capillary blood flow of upper limbs in
patients with secondary Raynaud's syndrome].
AB - The article discusses the effects of diosmin and hesperidin on capillary blood
flow in patients with secondary Raynaud's syndrome (RS). Raynaud's syndrome a
difficult problem of modern angiology, since in its development there is a large
range of disorders of the capillary blood flow of the limbs. Currently, the main
way of therapy in patients with secondary Raynaud's syndrome is the use of either
calcium channel blockers (if angiospastic stage of the disease), or
prostaglandins of group E1 (with tropho-paralytic stage of secondary RS).
However, pharmacological effects of calcium channel blockers (vasodilation) and
prostaglandins (vasodilation, antiproliferative, anti-inflammatory etc.) do not
allow impact on all violations of capillary blood flow, occurs when the Raynaud's
syndrome. In this regard, the task was to study the reaction of capillary blood
flow of the fingers of the hands on the concomitant use of drugs based on diosmin
and hesperidin. A prerequisite for the use of a combination of diosmin and
hesperidin in the treatment of RS was based on data about their impact on the
state of the venous segment of the capillary bed and perivascular oedema. To
conduct the study was established two groups of patients (22 in each group). The
main criterion for inclusion of patients in the study was the presence of newly
identified Raynaud's syndrome of angiospastic or tropho-paralytic stage of the
disease. The main exclusion criteria was the presence of necrotic stage of the
disease. In the first group of patients therapy was carried out using only
vasodilators. In the second group (comparison group) with the addition of a
combination of diosmin and hesperidin (tablets Venarus used in a dose 500 mg 2
times per day). The condition of capillary blood flow in this study was estimated
by the method of videocapillaroscopy (VCS). Statistical data processing was
performed using a criterion of statistical significance (P-value). The study
revealed the significant impact of a combination of diosmin and hesperidin for
parameters of capillary blood flow that correlated with clinical improvements -
reduction of oedema of the fingers of the hands.
PMID- 28514384
TI - [Innovative endoscopic technologies in multi-field medical facility].
AB - The modern clinical practice is characterized by intensive introduction of
innovative technologies for improving treatment and diagnostic procedures,
minimizing their impact on the patient, complications rate and economic reasons.
One of the priorities in this area is both diagnostic and therapeutic endoscopy.
The degree of practical use of innovative endoscopic technologies depends on not
only the quality of care, but also their economic reasons. Endoscopic treatment
has become the method of choice for gastrointestional bleeding, extraction of
foreign bodies, obstructive jaundice, polyps of the gastrointestinal tract,
achalasia, esophageal strictures, etc. So, the current state of scientific and
technical advances have made minimally invasive surgical intervention one of the
main direction of development of surgery. The further improvement will be
considered integration of minimally invasive and information technologies. The
widespread introduction of minimally invasive surgical techniques in clinical
practice indicates their undoubted efficiency and availability, especially in the
multidisciplinary hospitals that provide various types of specialized high
technological medical care. This allows to embody the principle of
multidisciplinary and personalized approach in the treatment of patients. The
main result of such practices is to reduce the duration of inpatient treatment, a
significant reduction in the degree of invasive impact and risk of surgical
interventions, diagnostic interventions and operations in a 'one-day hospital',
with a total increase of efficiency of surgical treatment, and with high quality
of life of patients.
PMID- 28514386
TI - [Validity of test scales for neurocognitive and psychoemotional testing in
patients with surgical pathology of precerebral arteries].
PMID- 28514387
TI - [Postoperative abdominal hernia: a modern view on incidence and
etiopathogenesis].
PMID- 28514388
TI - [Conversion in laparoscopic surgery for colorectal cancer].
PMID- 28514389
TI - [Acute bleeding from upper gastrointestinal tract due to splenic artery
pseudoaneurysm in a cavity of pancreatic pseudocyst].
PMID- 28514390
TI - [Gangliocytic paraganglioma of the duodenum].
PMID- 28514391
TI - [Ectopic liver tissue in gallbladder's wall].
PMID- 28514392
TI - [Direct oral anticoagulants in atrial fibrillation patients aged 75 years or
older: Efficacy and safety balance].
AB - Atrial fibrillation (AF) is one of the most common heart rhythm disorders in the
population. Researchers revealed a direct relationship between their incidence
and a patient's age long ago. One of the most challenging issues of clinical
practice in patients with AF is anticoagulant therapy used in the so-called very
elderly patients aged 75 years and older when age itself is a risk factor for
developing both thromboembolic and hemorrhagic events due to anticoagulants,
regardless of the mechanism of action of the latter. However, scientific data
regarding the treatment and prevention of thromboembolic events in elderly and
senile patients with AF are very scarce and often uninformative. The data from
the EURObservational Research Programme-Atrial Fibrillation Registry Pilot Phase
(EORP-AF Pilot) and the randomized clinical studies RELY, ROCKET AF, ARISTOTLE,
and AVERROES were analyzed to identify the most safe and most effective
anticoagulant for elderly patients (over 75 years). Relying on the analyses of
literature data, the authors propose an algorithm based on clinical
characteristics for choosing the anticoagulant for patients older than 75 years.
PMID- 28514393
TI - [Subtraction CT angiopulmonographic assessment of the vascular bed and lung
perfusion in patients with chronic thromboembolic pulmonary hypertension: A pilot
study].
AB - AIM: To evaluate the vascular bed and lung perfusion in patients with chronic
thromboembolic pulmonary hypertension (CTEPH) by computed tomography (CT) and to
compare the severity of pulmonary arterial (PA) thrombotic lesions concurrent
with parenchymal perfusion disorders with angiopulmonographic findings and
clinical and hemodynamic characteristics. SUBJECTS AND METHODS: In the period
from November 2015 to May 2016, 22 patients (7 men, 15 women) aged 27 to 67 years
with a verified diagnosis of CTEPH were examined using an Aquilion ONE VISION
Edition 640 (Toshiba Medical Systems, Japan) CT scanner with a 320-row detector.
Perfusion defect in this study was evaluated with the new software allowing one
to combine contrast and contrast-free images by a subtraction method. CT data
analysis included visual assessment of the vascular bed and lung parenchyma and
quantitative assessment with perfusion map construction and semi-automatic
determination of the obstruction index (OI) and perfusion defect index (PDI). OI
was compared with PDI and mean LA pressure according to the data of right heart
catheterization and 6-minute walk test. RESULTS: A statistically significant
correlation was found between OI and PDI in patients with CTEPH (Pearson r=0.56;
p=0.0065). There were no relationships between mean LA pressure and vascular
perfusion indices (OI and PDI) or between vascular perfusion parameters and 6
minute walk test results. CONCLUSION: CT angiopulmonography in conjunction with
pulmonary perfusion assessment (within one study) allows evaluation of the
severity of vascular lesions and perfusion disorders and determination of the
efficiency of treatment in patients with CTEPH.
PMID- 28514394
TI - [The diagnostic value of measuring the momentary blood flow reserve versus non
invasive methods to detect myocardial ischemia in assessing the functional
significance of borderline coronary artery stenoses].
AB - AIM: To estimate the diagnostic value of measuring the momentary blood flow
reserve (MBFR) versus the surrogate non-invasive standard (SNS) for myocardial
ischemia verification (MIV) (a combination of stress echocardiography and single
photon emission computed tomography). SUBJECTS AND METHODS: The investigation
enrolled 50 patients with stable angina in the presence of chronic coronary heart
disease (CHD) or suspected CHD, in whom coronary angiography (CA) revealed
borderline coronary stenoses (50-70% lumen diameters). The examination algorithm
had two options. In one option, when included in the study, patients had already
CA results not older than 1 month, and MBFR was measured 4-7 days after non
invasive stress tests. In the other option, MBFR in the area of borderline
coronary artery stenosis was measured simultaneously with CA; and the noninvasive
stress tests were carried out in the following week. A total of 74 coronary
stenoses were examined. RESULTS: SNS for MIV was positive in 14 (28%) patients.
When comparing with the non-invasive methods of myocardial ischemia verification,
the area under the ROC curve for MBFR was 0.961+/-0.019 (95% confidence interval,
0.888-0.992). The optimal cut-point was 0.92, which is corresponded by a
sensitivity of 100% and a specificity of 84%. CONCLUSION: When compared with SNS
for MIV, the method for measuring MBFR has a high diagnostic accuracy.
PMID- 28514395
TI - [Impact of shock-wave therapy on the clinical and functional status of patients
with coronary heart disease].
AB - AIM: To study of the impact of shock-wave therapy (SWT) on the functional status
of patients with coronary heart disease (CHD). SUBJECTS AND METHODS: Thirty-four
CHD patients (including 33 men) with left ventricular (LV) asynergic segments, as
evidenced by echocardiography (EchoCG), were examined. Their mean age was 60.1+/
1.76 years. All the patients received a SWT cycle according to the standard
scheme. The patient examination protocol involved EchoCG, dobutamine EchoCG,
treadmill exercise EchoCG, and tissue Doppler EchoCG, which were performed at
baseline, immediately and one month after the end of a SWT cycle. RESULTS:
Following a SWT cycle, all the patients were noted to have a significant decrease
in mean angina pectoris and heart failure functional classes and in the frequency
of daily intake of nitrates. EchoCG showed that at baseline the LV ejection
fraction (EF) was 51.1+/-1.02%; end- diastolic volume index, 71.5+/-3.6 ml/m2;
end-systolic volume index, 34.4+/-2.2 ml/m2. According to exercise EchoCG, the
tolerance threshold was 6.4+/-0.1 Mets (Bruce protocol); the total exercise time
of 5.05+/-0.23 min was achieved in an average of 75.2+/-1.32%. Immediately and
one month after a SWT cycle, there was an increment in EF from 51.1+/-1.02 to
55+/-0.8 and 57+/-1.7%, respectively; a substantial increase in the tolerance
threshold to 8.17+/-0.24 and 9.45+/-0.34 Mets, as compared to the baseline
values. The exercise time increased up to 6.41+/-0.17 and 7.7+/-0.29 min
immediately and one month after SWT, respectively. The increment in EF in
response to exercise was 8.54+/-2.12, 14+/-1.5, and 16+/-1.2% at baseline,
immediately and one month after SWT, respectively. Moreover, myocardial
relaxation and diastolic function improved. CONCLUSION: Shock-wave therapy in
patients with CHD is accompanied by their improved functional status, which is
manifested by increased tolerance threshold and exercise duration, a rise in rest
and exercise LV EF, better relaxation of LV, and its diminished stiffness.
PMID- 28514396
TI - [Long-term results of different approaches to revascularization in non-ST-segment
elevation acute coronary syndrome and multiple coronary atherosclerosis].
AB - AIM: To assess the long-term results of different approaches to treating patients
with non-ST-segment elevation acute coronary syndrome (NSTE ACS) and multivessel
coronary artery disease (MVCAD). SUBJECTS AND METHODS: A total of 150 patients
with NSTE ACS, in whom coronary angiography revealed MVCAD, were examined. The
patients were divided into 3 groups according to the selected treatment policy:
1) percutaneous coronary intervention (PCI) (n=91 (60.6%)); 2) coronary artery
bypass grafting (CABG) (n=40 (26.6%)); and 3) only medical treatment (n=9 (6%)).
The mean follow-up was 27.6+/-3.5 months. RESULTS: The medical treatment policy
in this patient sample demonstrates the worst results, with the majority of
cardiovascular events developing in the hospital period. PCI in patients with
NSTE ACS and multiple coronary atherosclerosis has a number of objective
limitations in this patient sample, leading to suboptimal treatment outcome.
CONCLUSION: The use of CABG or PCI as a myocardial revascularization technique in
patients with NSTE ACS and MVCAD is characterized by a comparable satisfactory
survival in the hospital and long-term follow-up periods. 12% of patients do not
receive revascularization due to the extremely high risk from any of coronary
blood restoring methods, which results in very many deaths largely occurring
during the hospital period.
PMID- 28514397
TI - [Vascular permeability and intravascular erythrocyte aggregation in young people
after smoking cessation].
AB - AIM: To study the parameters of microcirculation and permeability of the
microvessels in young people who have ceased smoking. SUBJECTS AND METHODS: The
study enrolled 35 healthy young adults (male to female ratio, 20:15; mean age,
21.71+/-0.46 years) who had stopped smoking 1 month to 10 years (mean 2.63+/-0.43
years) ago. The compared group consisted of 16 smokers (male to female ratio,
6:10; mean age, 21.62+/-0.72 years) and 29 non-smokers (male to female ratio,
8:21; mean age, 21.62+/-0.48 years). Computer-assisted video biomicroscopy of the
bulbar conjunctiva was performed. When the results were assessed, attention was
drawn to a change in the degree and extent of intravascular erythrocyte
aggregation (IVEA) and vessel wall permeability. RESULTS: As compared to the
smokers, those who had quit smoking showed a decrease in the degree of IVEA in
the arterioles (p1=0. 044, van der Waerden test), its prevalence in the central,
transitional, and perilimbar regions (p1<0.0001), and a decline in the number of
conjunctival areas that exhibited IVEA (2.2 and 3.437; p1=0.0002). Those who had
given up smoking versus the smokers were found to have more rarely local foci of
conjunctival edema (formation of veils; p1=0.0217). CONCLUSION: In the young
people who have ceased smoking versus the smokers, IVEA decreases and
miscovascular permeability restores.
PMID- 28514398
TI - [Structural features of the lipid bilayer of the red blood cell membrane in
people with isolated hypercholesterolemia without coronary artery disease and in
patients with coronary artery disease].
AB - AIM: To identify the specific features of modifying the lipid composition of the
red blood cell membrane in people with isolated hypercholesterolemia without
coronary heart disease (CHD) and in CHD patients with different functional
classes of angina pectoris. SUBJECTS AND METHODS: 92 men with Functional Class II
IV stable angina, 22 men with isolated hypercholesterolemia (HC) without CHD, and
18 healthy men with normal cholesterol levels were examined. Blood plasma
cholesterol levels were determined in all the examinees. The erythrocyte membrane
was examined for the levels of lipid peroxidation (LPO) products, free
cholesterol, calcium, and phospholipid fractions and for the activity of Na+/K+-,
Mg2+- and Ca2+-ATPases; a bicycle exercise test was carried out. RESULTS: As
compared with persons with normal blood cholesterol levels, the examinees with HC
without CHD were found to have higher levels of LPO products, lower levels of
readily oxidizable phospholipid fractions, decreased activity of membrane-bound
Na+/K+-, Mg2+-, and Ca2+-ATPases, and elevated concentrations of free cholesterol
and calcium in the red blood cell membrane. Having the pronounced activity of
free radical oxidation, the patients with CHD were detected to have deeper
similar structural changes in the cell membrane, which became more severe with a
larger number of affected coronary arteries. CONCLUSION: The findings suggest
that the lipid structure of the cell membrane undergoes changes associated with
its functional depression just at the preclinical stage of atherogenesis.
Biomembrane structural modification in patients with angina pectoris progresses
in proportion to the number of affected coronary arteries, by limiting the
functional reserve of the cell and whole body.
PMID- 28514399
TI - [Disaccharidase deficiency and functional bowel diseases].
AB - AIM: To elucidate the role of intestinal carbohydrases (glucoamylase, maltase,
sucrose, and lactase) in the etiology and pathogenesis of functional bowel
diseases (FBD). SUBJECTS AND METHODS: 74 patients (36 men and 38 women) aged 18
to 50 years with FBD were examined. According to Rome IV criteria (2016), there
was diarrhea-predominant irritable bowel syndrome (IBS) in 21 patients,
functional diarrhea (FD) in 33, constipation-predominant IBS in 6, functional
constipation (FC) in 4, and mixed IBS in 10. The activity of carbohydrases in the
small intestine mucosa (SIM) was investigated by the Dahlquist method modified by
Trinder in the duodenal biopsy specimens obtained during
esophagogastroduodenoscopy. RESULTS: Lactase deficiency was identified in 87.8%
of the patients; maltase deficiency in 48.6%; sucrose deficiency in 51.3%; and
glucoamylase deficiency in 85.1%. The activity of all the investigated enzymes
was reduced in 23 (31.1%) patients with FBD; deficiency of 1-3 carbohydrases was
found in 47 (63.5%). Normal enzymatic activity was established in 4 (5.4%)
patients. CONCLUSION: In the majority of patients with FBD, the intestinal
symptoms are caused by the decreased activity of SIM carbohydrases. Therefore,
disaccharidase deficiency associated with an established damaging agent
(nonsteroidal anti-inflammatory drugs, antibiotics, acute intestinal infections,
etc.) should be considered to be a more precise diagnosis.
PMID- 28514400
TI - [Comparative characteristics of patients with gastroesophageal reflux disease in
the age aspect].
AB - AIM: To compare the characteristics of patients with gastroesophageal reflux
disease (GERD) by age groups, a wide range of clinical signs, including life-of
quality (QOL) indicators, and instrumental findings. SUBJECTS AND METHODS: A
total of 110 patients aged 18 to 86 years with GERD were examined in accordance
with the standard protocol. Two groups with equal numbers of patents were formed.
A study group included elderly and senile patients and a control group consisted
of young and adult ones. RESULTS: The elderly patients with GERD were observed to
have a number of age-related clinical features and age-unrelated symptoms. The
scores in the scales characterizing the physical health component and those in
the general health and vital activity scales were markedly decreased in patients
older than 60 years of age. No age-related statistically significant differences
were found in the esophageal, gastric, and duodenal mucosae. Daily pH-metry in
the elderly showed indirect evidence for esophageal hypomotor dyskinesia in the
predominance of alkaline refluxes. CONCLUSION: The cohort of elderly patients
with GERD was ascertained to have statistically significant clinical
characteristics, and QOL and pH-metry indicators, which will be able to improve
methods for diagnosis and early prevention in this age group.
PMID- 28514401
TI - [Differentiation therapy for non-acidic gastroesophageal reflux disease].
AB - AIM: To investigate the clinical and pathogenetic features of the non-acidic
types of gastroesophageal reflux disease (GERD) and to evaluate the impact of
combined therapy versus monotherapy on the course of this disease. SUBJECTS AND
METHODS: The investigation enrolled 62 patients with non-acidic GERD. The follow
up period was 6 weeks. The patients were divided into 2 groups: 1) weakly acidic
gastroesophageal refluxes (GER); 2) weakly alkaline GER. Then each group was
distributed, thus making up 4 groups: 1) 19 patients with weakly acidic GER who
received monotherapy with rabeprazole 20 mg/day; 2) 21 patients with weakly
acidic GER had combined therapy with rabeprazole 20 mg and itopride; 3) 8
patients with weakly alkaline GER who received ursodeoxycholic acid (UDCA)
monotherapy; and 4) 14 patients with weakly alkaline GER who had combined therapy
with UDCA and itopride, The clinical symptoms of the disease, the endoscopic
pattern of the upper gastrointestinal tract (GIT) mucosa, histological changes in
the esophageal and gastric mucosa, and the results of 24-hour impedance pH
monitoring were assessed over time. RESULTS: During differentiation therapy, the
majority of patients reported positive clinical changes and an improved or
unchanged endoscopic pattern. Assessment of impedance pH monitoring results
revealed decreases in the overall number of GERs, the presence of a bolus in the
esophagus, and the number of proximal refluxes. These changes were noted not only
in patients taking proton pump inhibitors (PPIs), but also in those treated with
UDCA monotherapy or combined PPI and prokinetic therapy. CONCLUSION: A
differentiated approach to non-acidic GER treatment contributes to its
efficiency. Adding the prokinetic itomed (itopride hydrochloride) to PPI therapy
in a patient with weakly acidic GER enhances the efficiency of treatment, by
positively affecting upper GIT motility. The mainstay of therapy for GERD with a
predominance of weakly alkaline refluxes is UDCA, the combination of the latter
and the prokinetic can exert a more pronounced effect on the clinical and
endoscopic pattern and upper GIT motility.
PMID- 28514402
TI - [Psychoemotional and autonomic states in patients with cholelithiasis].
AB - AIM: To investigate the psychoemotional and autonomic states of patients with
biliary system diseases and to determine their significance in the development of
cholelithiasis. SUBJECTS AND METHODS: A total of 396 patients with stage 1
cholelithiasis were examined. The results of hepatobiliary ultrasonography,
multifractional duodenal probing, followed by macroscopic, microscopic, and
biochemical examinations of bile (the total concentration of bile acids and
cholesterol, by subsequently calculating the cholate-cholesterol ratio) were used
to verify the diagnosis. The functional state of the hepatobiliary system was
evaluated by dynamic echocholecystography and dynamic hepatobiliscintigraphy. To
characterize the emotional state, the investigators applied indicators of the
motivational sphere and orientation of an individual and his/her mental state,
such as reactive anxiety, personal anxiety, the levels of depression and
neuroticism, and intra-, extraversion. The autonomic state was determined from
autonomic tone, autonomic reactivity, and autonomic support. RESULTS: Biliary
lithogenesis was found to be related to psychoemotional and autonomic states. In
cholelithiasis, there was an increase in reactive and personal anxiety and a
predominance of diminished parasympathetic and perverted sympathetic autonomic
reactivity. The signs of emotional instability and autonomic dystonia were shown
to increase with age and the degree of an autonomic response depended on the
severity of mental and emotional disorders. CONCLUSION: The results of these
comprehensive studies can reveal new pathophysiological patterns of lithogenic
bile formation and enhance our understanding of the pathogenesis of
cholelithiasis.
PMID- 28514403
TI - [Chronic constipation in the practice of a therapist: Features of therapy for
comorbidity].
AB - AIM: To evaluate the clinical efficacy of laxatives with different
pharmacological effects in the combination therapy in patients with chronic
constipation (CC) concurrent with obesity, hypertensive disease, and type 2
diabetes mellitus (DM). SUBJECTS AND METHODS: A total of 110 people (45 men, 65
women) aged 45 to 72 years with CC in the presence of concomitant diseases: grade
1 or 2 hypertensive disease + obesity + type 2 DM. The investigators determined
the severity of abdominal pain syndrome and flatulence, by indicating the mean
frequency of defecations per week and fecal consistency according to the Bristol
stool scale; anthropometric parameters; serum biochemistry tests; and serum
lipoprotein phenotyping. Quality of life was assessed by the SF-36 questionnaire.
The patients were divided into 3 groups according their use of agents: 1) dietary
fiber (psyllium); 2) osmotic laxatives (disaccharides); 3) osmotic laxatives
(polyethylene glycol). RESULTS: The patients taking psyllium to treat
constipation showed an increasing frequency of defecations and normalization of
stool consistency. Incorporating psyllium into combination therapy was
accompanied by a significant decrease in the levels of total cholesterol and low
density lipoprotein cholesterol. A similar trend was observed for serum
triglycerides. The patients receiving combination therapy including other
laxatives displayed no significant differences between lipid metabolic parameters
at the beginning and after the end of treatment. CONCLUSION: The whole complex of
properties of psyllium (Mucofalk) can be fully realized in patients with
comorbidity and chronic constipation, which is accompanied not only by the
normalization of bowel emptying, but also by marked positive changes in the main
lipid metabolic parameters and by a reduction in overweight.
PMID- 28514404
TI - [Emotional impairments and their correction in patients with migraine].
AB - AIM: To study emotional impairments in patients with migraine and to evaluate the
efficiency of Noophen therapy for this pathology. SUBJECTS AND METHODS: 63
patients aged 18 to 45 years with migraine without aura were examined. 56
patients used prophylactic antimigraine therapy: Group 1 (n = 26) received
metoprolol and Group 2 took metoprolol in combination with Noophen. RESULTS: The
patients with migraine had a significantly higher level of alexithymia than the
controls. Concomitant anxiety disorders were found in 47 (74.6%) cases. The study
provided evidence that the treatment was highly effective in Group 2 that
exhibited a more pronounced decrease in pain intensity, a greater reduction in
the levels of anxiety, and more vital activity. CONCLUSION: The results of this
study allow a conclusion that emotional impairments are implicated in the
pathogenesis and clinical presentations of migraine and that it is appropriate to
use Noophen for the treatment of this pathology.
PMID- 28514405
TI - [Stable high interleukin-17A concentration in patients with ankylosing
spondylitis treated with tumor necrosis factor-alpha inhibitors during a year].
AB - AIM: To assess changes in the concentration of interleukin-17A (IL-17A) in
patients with ankylosing spondylitis (AS) treated with tumor necrosis factor
alpha (TNFalpha) inhibitors during a year. SUBJECTS AND METHODS: Examinations
were made in 30 patients (22 (73.3%) men) aged 38.35+/-9.19 years with AS
(modified New-York criteria, BASDAI >=4.0; AS duration, 11.4+/-9.6 years) and in
20 healthy individuals (12 (60%) men) aged 40.1+/-7.7 years) (a control group).
All the patients were treated with infliximab (remicade, MSD) 5 mg/kg body weight
during a year according to the recommended regimen. BASDAI and ASDAS were
calculated; C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and
TNFalpha and IL-17A concentrations were measured before and 52+/-2 weeks after
TNFalpha inhibitors treatment. BASDAI/ASDAS improvement, ESR and CRP decreases;
ASAS20/40 responses, ASAS partial remission, and an ASDAS improvement were
estimated. RESULTS: In the patients with AS, the concentrations of TNFalpha and
IL-17A were higher than those in the healthy individuals (p < 0.000). Twelve
(40%) AS patients treated with TNFalpha inhibitors achieved ASAS partial
remission. The average estimated back pain, ASDAS and BASDAI scores, and CRP and
ESR substantially reduced (p<0.000 for all). The concentration of TNFalpha
decreased from 17.8+/-7.6 to 7.3+/-3.2 pg/ml (p<0.000). The IL-17A level was
28.4+/-14.4 and 32.1+/-12.2 pg/ml before and after the treatment, respectively.
The baseline level of IL-17A was lower in the patients with AS who had achieved
remission than that in those who had not (p=0.01). CONCLUSION: The improvement
due to one-year AS treatment with TNFalpha inhibitors is not associated with the
reduction of IL-17A concentrations. In the patients who failed to achieve ASAS
partial remission, the baseline and final serum concentrations of IL-17A were
higher than in those who achieved the remission.
PMID- 28514406
TI - [A case of primary diagnosis of patent ductus arteriosus at the age of 75 years].
AB - The paper describes a case of primary diagnosis of functioning patent ductus
arteriosus in a 75-year-old female patient.
PMID- 28514407
TI - [Osteoprotegerin is a new marker of cardiovascular diseases].
AB - Osteoprotegerin (OPG) is a glycoprotein that is a representative of the tumor
necrosis factor-alpha receptor superfamily. Information about the possible role
of OPG in the development of cardiovascular diseases has begun to appear in the
literature in recent years. This review discusses the role of increasing the
level of OPG in the development and progression of atherosclerosis and as a
consequence of coronary heart disease and chronic heart failure.
PMID- 28514408
TI - [Asymptomatic atherosclerosis of the brachiocephalic arteries: Current approaches
to diagnosis and treatment].
AB - Acute cerebrovascular accident (ACVA) and transient ischemic attack are among the
leading causes of morbidity, disability, and mortality in the Russian Federation
and the world. Ischemic strokes account for 70-80% of all ACVAs, with 20-30% of
them being associated with stenotic atherosclerosis of the brachiocephalic
arteries (BCA). The paper describes modern views on the problem of asymptomatic
BCA atherosclerosis and considers the possibilities of identifying risk groups
among the patients with asymptomatic atherosclerosis of the BCA.
PMID- 28514410
TI - [Cryoglobulinemic vasculitis in chronic hepatitis C: Genetic aspects].
AB - Cryoglobulinemia (CG) is detected in more than 50% of patients with chronic
hepatitis C (CHC); however, only 15-25% of them develop cryoglobulinemic
vasculitis (CV) that is a systemic vasculitis due to the formation of immune
deposits, which affects small (less than medium-sized) vessels and which is
frequently fatal for the patient. The causes of CG only in some patients with CHC
and the pathogenesis of CV remain unstudied; however, the accumulated data allow
one to identify the special contribution of the patient's genetic factors to the
development of the disease. The paper considers the genetic aspects of the
development of CG and CV in CHC.
PMID- 28514409
TI - [New opportunities for the prevention of gastric cancer].
AB - The approvals and provisions of the Management of Helicobacter pylori infection
the Maastricht V/ Florence Consensus Report and those of the Kyoto Global
Consensus Conference on H. pylori-associated gastritis, concerning with the
primary and secondary prevention of gastric cancer (GC), unambiguously suggest
that H. pylori infection is the most important risk factor of GC. Accordingly,
the basis for the primary and secondary prevention of GC is the optimization of
H. pylori eradication therapy. The clear direct relationship of the risk of GC to
the severity and extent of atrophic gastritis, intestinal metaplasia and
dysplasia and no reversal of intestinal metaplasia and dysplasia in the presence
of H. pylori eradication presume that gastroprotective agents should be used for
primary and secondary prevention. Experimental and clinical findings can lead to
the conclusion that rebamipide is a highly effective and safe agent for the
primary and secondary prevention of GC in patients with and without H. pylori
infection, by optimizing anti-Helicobacter therapy, its anti-inflammatory effect
and ability to restore the cellular structure of the gastric epithelium.
PMID- 28514411
TI - [Langerhans cell histiocytosis: Skin diseases and visceral lesions].
AB - Langerhans cell histiocytosis (LCH) is a rare clonal proliferative disorder that
belongs to class I histiocytoses and is characterized by infiltration of one or
many organs by Langerhans cells to form granulomas. The literature analysis could
identify a lot of etiological, pathogenetic, and trigger factors and mechanisms
for LCH development, which determine the diversity of the clinical picture and
course of the disease. The clinical manifestations of LCH are very variable and
depend on the severity of lesions and the age of patients. In addition to skin
lesions, there is involvement of one or more visceral organs. Difficulties in
diagnosing the disease lead to statistical variations of LCH in different
countries of the world and require more attention by physicians of all
specialties.
PMID- 28514413
TI - University spin-offs.
PMID- 28514412
TI - Therapeutic developments: Masters of medicine.
PMID- 28514414
TI - Clinical devices and services: Repair shops.
PMID- 28514416
TI - Energy: Powering change.
PMID- 28514415
TI - Materials and engineering: Rebuilding the world.
PMID- 28514417
TI - Software: Picture perfect.
PMID- 28514419
TI - Erratum: Full antagonism of the estrogen receptor without a prototypical ligand
side chain.
PMID- 28514421
TI - Small-molecule phenotypic screening with stem cells.
PMID- 28514422
TI - Shaping embryonic development.
PMID- 28514424
TI - Corrigendum: Full antagonism of the estrogen receptor without a prototypical
ligand side chain.
PMID- 28514418
TI - Small-molecule pheromones and hormones controlling nematode development.
AB - The existence of small-molecule signals that influence development in
Caenorhabditis elegans has been known for several decades, but only in recent
years have the chemical structures of several of these signals been established.
The identification of these signals has enabled connections to be made between
these small molecules and fundamental signaling pathways in C. elegans that
influence not only development but also metabolism, fertility, and lifespan.
Spurred by these important discoveries and aided by recent advances in
comparative metabolomics and NMR spectroscopy, the field of nematode chemistry
has the potential to expand dramatically in the coming years. This Perspective
will focus on small-molecule pheromones and hormones that influence developmental
events in the nematode life cycle (ascarosides, dafachronic acids, and
nemamides), will cover more recent work regarding the biosynthesis of these
signals, and will explore how the discovery of these signals is transforming our
understanding of nematode development and physiology.
PMID- 28514425
TI - Signal Transduction: Notch catches a Jagged edge.
PMID- 28514428
TI - Unraveling cell-to-cell signaling networks with chemical biology.
PMID- 28514429
TI - Optogenetics: Switching with red and blue.
PMID- 28514427
TI - Illuminating developmental biology through photochemistry.
AB - Developmental biology has been continually shaped by technological advances,
evolving from a descriptive science into one immersed in molecular and cellular
mechanisms. Most recently, genome sequencing and 'omics' profiling have provided
developmental biologists with a wealth of genetic and biochemical information;
however, fully translating this knowledge into functional understanding will
require new experimental capabilities. Photoactivatable probes have emerged as
particularly valuable tools for investigating developmental mechanisms, as they
can enable rapid, specific manipulations of DNA, RNA, proteins, and cells with
spatiotemporal precision. In this Perspective, we describe optochemical and
optogenetic systems that have been applied in multicellular organisms, insights
gained through the use of these probes, and their current limitations. We also
suggest how chemical biologists can expand the reach of photoactivatable
technologies and bring new depth to our understanding of organismal development.
PMID- 28514430
TI - Erratum: A Vibrio cholerae autoinducer-receptor pair that controls biofilm
formation.
PMID- 28514433
TI - The genetic microscope.
PMID- 28514434
TI - Q&A: Jim McCluskey.
PMID- 28514435
TI - Career guide Melbourne.
PMID- 28514436
TI - Q&A: Victoria Blair.
PMID- 28514432
TI - The perception of strigolactones in vascular plants.
AB - Small-molecule hormones play central roles in plant development, ranging from
cellular differentiation and organ formation to developmental response
instruction in changing environments. A recently discovered collection of related
small molecules collectively called strigolactones are of particular interest, as
these hormones also function as ecological communicators between plants and fungi
and between parasitic plants and their hosts. Advances from model plant systems
have begun to unravel how, as a hormone, strigolactone is perceived and
transduced. In this Review, we summarize this information and examine how
understanding strigolactone hormone signaling is leading to insights into
parasitic plant infections. We specifically focus on how the development of
chemical probes can be used in combination with model plant systems to dissect
strigolactone's perception in the parasitic plant Striga hermonthica. This
information is particularly relevant since Striga is considered one of the
largest impediments to food security in sub-Saharan Africa.
PMID- 28514437
TI - China's Silicon Valley.
PMID- 28514438
TI - Conversion of adult endothelium to immunocompetent haematopoietic stem cells.
AB - Developmental pathways that orchestrate the fleeting transition of endothelial
cells into haematopoietic stem cells remain undefined. Here we demonstrate a
tractable approach for fully reprogramming adult mouse endothelial cells to
haematopoietic stem cells (rEC-HSCs) through transient expression of the
transcription-factor-encoding genes Fosb, Gfi1, Runx1, and Spi1 (collectively
denoted hereafter as FGRS) and vascular-niche-derived angiocrine factors. The
induction phase (days 0-8) of conversion is initiated by expression of FGRS in
mature endothelial cells, which results in endogenous Runx1 expression. During
the specification phase (days 8-20), RUNX1+ FGRS-transduced endothelial cells
commit to a haematopoietic fate, yielding rEC-HSCs that no longer require FGRS
expression. The vascular niche drives a robust self-renewal and expansion phase
of rEC-HSCs (days 20-28). rEC-HSCs have a transcriptome and long-term self
renewal capacity similar to those of adult haematopoietic stem cells, and can be
used for clonal engraftment and serial primary and secondary multi-lineage
reconstitution, including antigen-dependent adaptive immune function. Inhibition
of TGFbeta and CXCR7 or activation of BMP and CXCR4 signalling enhanced
generation of rEC-HSCs. Pluripotency-independent conversion of endothelial cells
into autologous authentic engraftable haematopoietic stem cells could aid
treatment of haematological disorders.
PMID- 28514439
TI - Haematopoietic stem and progenitor cells from human pluripotent stem cells.
AB - A variety of tissue lineages can be differentiated from pluripotent stem cells by
mimicking embryonic development through stepwise exposure to morphogens, or by
conversion of one differentiated cell type into another by enforced expression of
master transcription factors. Here, to yield functional human haematopoietic stem
cells, we perform morphogen-directed differentiation of human pluripotent stem
cells into haemogenic endothelium followed by screening of 26 candidate
haematopoietic stem-cell-specifying transcription factors for their capacity to
promote multi-lineage haematopoietic engraftment in mouse hosts. We recover seven
transcription factors (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1 and SPI1) that are
sufficient to convert haemogenic endothelium into haematopoietic stem and
progenitor cells that engraft myeloid, B and T cells in primary and secondary
mouse recipients. Our combined approach of morphogen-driven differentiation and
transcription-factor-mediated cell fate conversion produces haematopoietic stem
and progenitor cells from pluripotent stem cells and holds promise for modelling
haematopoietic disease in humanized mice and for therapeutic strategies in
genetic blood disorders.
PMID- 28514440
TI - Extreme hydrothermal conditions at an active plate-bounding fault.
AB - Temperature and fluid pressure conditions control rock deformation and
mineralization on geological faults, and hence the distribution of earthquakes.
Typical intraplate continental crust has hydrostatic fluid pressure and a near
surface thermal gradient of 31 +/- 15 degrees Celsius per kilometre. At
temperatures above 300-450 degrees Celsius, usually found at depths greater than
10-15 kilometres, the intra-crystalline plasticity of quartz and feldspar
relieves stress by aseismic creep and earthquakes are infrequent. Hydrothermal
conditions control the stability of mineral phases and hence frictional
mechanical processes associated with earthquake rupture cycles, but there are few
temperature and fluid pressure data from active plate-bounding faults. Here we
report results from a borehole drilled into the upper part of the Alpine Fault,
which is late in its cycle of stress accumulation and expected to rupture in a
magnitude 8 earthquake in the coming decades. The borehole (depth 893 metres)
revealed a pore fluid pressure gradient exceeding 9 +/- 1 per cent above
hydrostatic levels and an average geothermal gradient of 125 +/- 55 degrees
Celsius per kilometre within the hanging wall of the fault. These extreme
hydrothermal conditions result from rapid fault movement, which transports rock
and heat from depth, and topographically driven fluid movement that concentrates
heat into valleys. Shear heating may occur within the fault but is not required
to explain our observations. Our data and models show that highly anomalous fluid
pressure and temperature gradients in the upper part of the seismogenic zone can
be created by positive feedbacks between processes of fault slip, rock fracturing
and alteration, and landscape development at plate-bounding faults.
PMID- 28514441
TI - PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour
immunity.
AB - Programmed cell death protein 1 (PD-1) is an immune checkpoint receptor that is
upregulated on activated T cells for the induction of immune tolerance. Tumour
cells frequently overexpress the ligand for PD-1, programmed cell death ligand 1
(PD-L1), facilitating their escape from the immune system. Monoclonal antibodies
that block the interaction between PD-1 and PD-L1, by binding to either the
ligand or receptor, have shown notable clinical efficacy in patients with a
variety of cancers, including melanoma, colorectal cancer, non-small-cell lung
cancer and Hodgkin's lymphoma. Although it is well established that PD-1-PD-L1
blockade activates T cells, little is known about the role that this pathway may
have in tumour-associated macrophages (TAMs). Here we show that both mouse and
human TAMs express PD-1. TAM PD-1 expression increases over time in mouse models
of cancer and with increasing disease stage in primary human cancers. TAM PD-1
expression correlates negatively with phagocytic potency against tumour cells,
and blockade of PD-1-PD-L1 in vivo increases macrophage phagocytosis, reduces
tumour growth and lengthens the survival of mice in mouse models of cancer in a
macrophage-dependent fashion. This suggests that PD-1-PD-L1 therapies may also
function through a direct effect on macrophages, with substantial implications
for the treatment of cancer with these agents.
PMID- 28514444
TI - Plant biology: An immunity boost combats crop disease.
PMID- 28514442
TI - Architecture of the human interactome defines protein communities and disease
networks.
AB - The physiology of a cell can be viewed as the product of thousands of proteins
acting in concert to shape the cellular response. Coordination is achieved in
part through networks of protein-protein interactions that assemble functionally
related proteins into complexes, organelles, and signal transduction pathways.
Understanding the architecture of the human proteome has the potential to inform
cellular, structural, and evolutionary mechanisms and is critical to elucidating
how genome variation contributes to disease. Here we present BioPlex 2.0
(Biophysical Interactions of ORFeome-derived complexes), which uses robust
affinity purification-mass spectrometry methodology to elucidate protein
interaction networks and co-complexes nucleated by more than 25% of protein
coding genes from the human genome, and constitutes, to our knowledge, the
largest such network so far. With more than 56,000 candidate interactions,
BioPlex 2.0 contains more than 29,000 previously unknown co-associations and
provides functional insights into hundreds of poorly characterized proteins while
enhancing network-based analyses of domain associations, subcellular
localization, and co-complex formation. Unsupervised Markov clustering of
interacting proteins identified more than 1,300 protein communities representing
diverse cellular activities. Genes essential for cell fitness are enriched within
53 communities representing central cellular functions. Moreover, we identified
442 communities associated with more than 2,000 disease annotations, placing
numerous candidate disease genes into a cellular framework. BioPlex 2.0 exceeds
previous experimentally derived interaction networks in depth and breadth, and
will be a valuable resource for exploring the biology of incompletely
characterized proteins and for elucidating larger-scale patterns of proteome
organization.
PMID- 28514443
TI - Cancer progression by reprogrammed BCAA metabolism in myeloid leukaemia.
AB - Reprogrammed cellular metabolism is a common characteristic observed in various
cancers. However, whether metabolic changes directly regulate cancer development
and progression remains poorly understood. Here we show that BCAT1, a cytosolic
aminotransferase for branched-chain amino acids (BCAAs), is aberrantly activated
and functionally required for chronic myeloid leukaemia (CML) in humans and in
mouse models of CML. BCAT1 is upregulated during progression of CML and promotes
BCAA production in leukaemia cells by aminating the branched-chain keto acids.
Blocking BCAT1 gene expression or enzymatic activity induces cellular
differentiation and impairs the propagation of blast crisis CML both in vitro and
in vivo. Stable-isotope tracer experiments combined with nuclear magnetic
resonance-based metabolic analysis demonstrate the intracellular production of
BCAAs by BCAT1. Direct supplementation with BCAAs ameliorates the defects caused
by BCAT1 knockdown, indicating that BCAT1 exerts its oncogenic function through
BCAA production in blast crisis CML cells. Importantly, BCAT1 expression not only
is activated in human blast crisis CML and de novo acute myeloid leukaemia, but
also predicts disease outcome in patients. As an upstream regulator of BCAT1
expression, we identified Musashi2 (MSI2), an oncogenic RNA binding protein that
is required for blast crisis CML. MSI2 is physically associated with the BCAT1
transcript and positively regulates its protein expression in leukaemia. Taken
together, this work reveals that altered BCAA metabolism activated through the
MSI2-BCAT1 axis drives cancer progression in myeloid leukaemia.
PMID- 28514445
TI - Blood: Education for stem cells.
PMID- 28514447
TI - Global translational reprogramming is a fundamental layer of immune regulation in
plants.
AB - In the absence of specialized immune cells, the need for plants to reprogram
transcription to transition from growth-related activities to defence is well
understood. However, little is known about translational changes that occur
during immune induction. Using ribosome footprinting, here we perform global
translatome profiling on Arabidopsis exposed to the microbe-associated molecular
pattern elf18. We find that during this pattern-triggered immunity, translation
is tightly regulated and poorly correlated with transcription. Identification of
genes with altered translational efficiency leads to the discovery of novel
regulators of this immune response. Further investigation of these genes shows
that messenger RNA sequence features are major determinants of the observed
translational efficiency changes. In the 5' leader sequences of transcripts with
increased translational efficiency, we find a highly enriched messenger RNA
consensus sequence, R-motif, consisting of mostly purines. We show that R-motif
regulates translation in response to pattern-triggered immunity induction through
interaction with poly(A)-binding proteins. Therefore, this study provides not
only strong evidence, but also a molecular mechanism, for global translational
reprogramming during pattern-triggered immunity in plants.
PMID- 28514446
TI - Identification of preoptic sleep neurons using retrograde labelling and gene
profiling.
AB - In humans and other mammalian species, lesions in the preoptic area of the
hypothalamus cause profound sleep impairment, indicating a crucial role of the
preoptic area in sleep generation. However, the underlying circuit mechanism
remains poorly understood. Electrophysiological recordings and c-Fos
immunohistochemistry have shown the existence of sleep-active neurons in the
preoptic area, especially in the ventrolateral preoptic area and median preoptic
nucleus. Pharmacogenetic activation of c-Fos-labelled sleep-active neurons has
been shown to induce sleep. However, the sleep-active neurons are spatially
intermingled with wake-active neurons, making it difficult to target the sleep
neurons specifically for circuit analysis. Here we identify a population of
preoptic area sleep neurons on the basis of their projection target and discover
their molecular markers. Using a lentivirus expressing channelrhodopsin-2 or a
light-activated chloride channel for retrograde labelling, bidirectional
optogenetic manipulation, and optrode recording, we show that the preoptic area
GABAergic neurons projecting to the tuberomammillary nucleus are both sleep
active and sleep promoting. Furthermore, translating ribosome affinity
purification and single-cell RNA sequencing identify candidate markers for these
neurons, and optogenetic and pharmacogenetic manipulations demonstrate that
several peptide markers (cholecystokinin, corticotropin-releasing hormone, and
tachykinin 1) label sleep-promoting neurons. Together, these findings provide
easy genetic access to sleep-promoting preoptic area neurons and a valuable entry
point for dissecting the sleep control circuit.
PMID- 28514448
TI - uORF-mediated translation allows engineered plant disease resistance without
fitness costs.
AB - Controlling plant disease has been a struggle for humankind since the advent of
agriculture. Studies of plant immune mechanisms have led to strategies of
engineering resistant crops through ectopic transcription of plants' own defence
genes, such as the master immune regulatory gene NPR1 (ref. 1). However, enhanced
resistance obtained through such strategies is often associated with substantial
penalties to fitness, making the resulting products undesirable for agricultural
applications. To remedy this problem, we sought more stringent mechanisms of
expressing defence proteins. On the basis of our latest finding that translation
of key immune regulators, such as TBF1 (ref. 3), is rapidly and transiently
induced upon pathogen challenge (see accompanying paper), we developed a 'TBF1
cassette' consisting of not only the immune-inducible promoter but also two
pathogen-responsive upstream open reading frames (uORFsTBF1) of the TBF1 gene.
Here we demonstrate that inclusion of uORFsTBF1-mediated translational control
over the production of snc1-1 (an autoactivated immune receptor) in Arabidopsis
thaliana and AtNPR1 in rice enables us to engineer broad-spectrum disease
resistance without compromising plant fitness in the laboratory or in the field.
This broadly applicable strategy may lead to decreased pesticide use and reduce
the selective pressure for resistant pathogens.
PMID- 28514449
TI - Human GLP-1 receptor transmembrane domain structure in complex with allosteric
modulators.
AB - The glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR)
are members of the secretin-like class B family of G-protein-coupled receptors
(GPCRs) and have opposing physiological roles in insulin release and glucose
homeostasis. The treatment of type 2 diabetes requires positive modulation of GLP
1R to inhibit glucagon secretion and stimulate insulin secretion in a glucose
dependent manner. Here we report crystal structures of the human GLP-1R
transmembrane domain in complex with two different negative allosteric
modulators, PF-06372222 and NNC0640, at 2.7 and 3.0 A resolution, respectively.
The structures reveal a common binding pocket for negative allosteric modulators,
present in both GLP-1R and GCGR and located outside helices V-VII near the
intracellular half of the receptor. The receptor is in an inactive conformation
with compounds that restrict movement of the intracellular tip of helix VI, a
movement that is generally associated with activation mechanisms in class A
GPCRs. Molecular modelling and mutagenesis studies indicate that agonist positive
allosteric modulators target the same general region, but in a distinct sub
pocket at the interface between helices V and VI, which may facilitate the
formation of an intracellular binding site that enhances G-protein coupling.
PMID- 28514450
TI - Evolutionary enhancement of Zika virus infectivity in Aedes aegypti mosquitoes.
AB - Zika virus (ZIKV) remained obscure until the recent explosive outbreaks in French
Polynesia (2013-2014) and South America (2015-2016). Phylogenetic studies have
shown that ZIKV has evolved into African and Asian lineages. The Asian lineage of
ZIKV was responsible for the recent epidemics in the Americas. However, the
underlying mechanisms through which ZIKV rapidly and explosively spread from Asia
to the Americas are unclear. Non-structural protein 1 (NS1) facilitates
flavivirus acquisition by mosquitoes from an infected mammalian host and
subsequently enhances viral prevalence in mosquitoes. Here we show that NS1
antigenaemia determines ZIKV infectivity in its mosquito vector Aedes aegypti,
which acquires ZIKV via a blood meal. Clinical isolates from the most recent
outbreak in the Americas were much more infectious in mosquitoes than the
FSS13025 strain, which was isolated in Cambodia in 2010. Further analyses showed
that these epidemic strains have higher NS1 antigenaemia than the FSS13025 strain
because of an alanine-to-valine amino acid substitution at residue 188 in NS1.
ZIKV infectivity was enhanced by this amino acid substitution in the ZIKV
FSS13025 strain in mosquitoes that acquired ZIKV from a viraemic C57BL/6 mouse
deficient in type I and II interferon (IFN) receptors (AG6 mouse). Our results
reveal that ZIKV evolved to acquire a spontaneous mutation in its NS1 protein,
resulting in increased NS1 antigenaemia. Enhancement of NS1 antigenaemia in
infected hosts promotes ZIKV infectivity and prevalence in mosquitoes, which
could have facilitated transmission during recent ZIKV epidemics.
PMID- 28514452
TI - Isotopic evidence of multiple controls on atmospheric oxidants over climate
transitions.
AB - The abundance of tropospheric oxidants, such as ozone (O3) and hydroxyl (OH) and
peroxy radicals (HO2 + RO2), determines the lifetimes of reduced trace gases such
as methane and the production of particulate matter important for climate and
human health. The response of tropospheric oxidants to climate change is poorly
constrained owing to large uncertainties in the degree to which processes that
influence oxidants may change with climate and owing to a lack of palaeo-records
with which to constrain levels of atmospheric oxidants during past climate
transitions. At present, it is thought that temperature-dependent emissions of
tropospheric O3 precursors and water vapour abundance determine the climate
response of oxidants, resulting in lower tropospheric O3 in cold climates while
HOx (= OH + HO2 + RO2) remains relatively buffered. Here we report observations
of oxygen-17 excess of nitrate (a proxy for the relative abundance of atmospheric
O3 and HOx) from a Greenland ice core over the most recent glacial-interglacial
cycle and for two Dansgaard-Oeschger events. We find that tropospheric oxidants
are sensitive to climate change with an increase in the O3/HOx ratio in cold
climates, the opposite of current expectations. We hypothesize that the observed
increase in O3/HOx in cold climates is driven by enhanced stratosphere-to
troposphere transport of O3, and that reactive halogen chemistry is also enhanced
in cold climates. Reactive halogens influence the oxidative capacity of the
troposphere directly as oxidants themselves and indirectly via their influence on
O3 and HOx. The strength of stratosphere-to-troposphere transport is largely
controlled by the Brewer-Dobson circulation, which may be enhanced in colder
climates owing to a stronger meridional gradient of sea surface temperatures,
with implications for the response of tropospheric oxidants and stratospheric
thermal and mass balance. These two processes may represent important, yet
relatively unexplored, climate feedback mechanisms during major climate
transitions.
PMID- 28514455
TI - Precision Psychiatry Meets Network Medicine: Network Psychiatry.
PMID- 28514456
TI - Correction of 95% CI in Table.
PMID- 28514457
TI - Omission in Funding/Support Section.
PMID- 28514453
TI - Chromatin states define tumour-specific T cell dysfunction and reprogramming.
AB - Tumour-specific CD8 T cells in solid tumours are dysfunctional, allowing tumours
to progress. The epigenetic regulation of T cell dysfunction and therapeutic
reprogrammability (for example, to immune checkpoint blockade) is not well
understood. Here we show that T cells in mouse tumours differentiate through two
discrete chromatin states: a plastic dysfunctional state from which T cells can
be rescued, and a fixed dysfunctional state in which the cells are resistant to
reprogramming. We identified surface markers associated with each chromatin state
that distinguished reprogrammable from non-reprogrammable PD1hi dysfunctional T
cells within heterogeneous T cell populations from tumours in mice; these surface
markers were also expressed on human PD1hi tumour-infiltrating CD8 T cells. Our
study has important implications for cancer immunotherapy as we define key
transcription factors and epigenetic programs underlying T cell dysfunction and
surface markers that predict therapeutic reprogrammability.
PMID- 28514451
TI - Structure of the full-length glucagon class B G-protein-coupled receptor.
AB - The human glucagon receptor, GCGR, belongs to the class B G-protein-coupled
receptor family and plays a key role in glucose homeostasis and the
pathophysiology of type 2 diabetes. Here we report the 3.0 A crystal structure of
full-length GCGR containing both the extracellular domain and transmembrane
domain in an inactive conformation. The two domains are connected by a 12-residue
segment termed the stalk, which adopts a beta-strand conformation, instead of
forming an alpha-helix as observed in the previously solved structure of the GCGR
transmembrane domain. The first extracellular loop exhibits a beta-hairpin
conformation and interacts with the stalk to form a compact beta-sheet structure.
Hydrogen-deuterium exchange, disulfide crosslinking and molecular dynamics
studies suggest that the stalk and the first extracellular loop have critical
roles in modulating peptide ligand binding and receptor activation. These
insights into the full-length GCGR structure deepen our understanding of the
signalling mechanisms of class B G-protein-coupled receptors.
PMID- 28514459
TI - Late-Life Depression and the Prodromes of Dementia.
PMID- 28514458
TI - Effect of Expedited Microneedle-Assisted Photodynamic Therapy for Field Treatment
of Actinic Keratoses: A Randomized Clinical Trial.
AB - Importance: Photodynamic therapy (PDT) is an effective and cosmetically favorable
treatment modality for actinic keratoses (AKs). However, prolonged incubation
times and pain associated with treatment are burdensome to the patient and a
hindrance to widespread use of PDT as standard field therapy for AK. Objective:
To evaluate efficacy and pain associated with microneedle expedited PDT. Design,
Setting, and Participants: The Microneedle Photodynamic Therapy II (MNPDT-II)
study was a randomized, single-blinded, split-face controlled, 2-arm clinical
trial. Thirty-three participants with AK on the face were recruited in a
university dermatology outpatient clinic from 2015 to 2016, and 32 participants
completed the study. Interventions: Participants were randomized into 2
incubations arms, either 10-minute or 20-minute aminolevulinic acid (ALA)
incubation times, after pretreatment with a microneedle roller (200 um) vs a sham
roller. They were blinded to the laterality of microneedle and sham roller
assignments. After incubation, they were exposed to blue light (Blu-U, Dusa
Pharmaceuticals) for 1000 seconds for a total fluence of 10 J/cm2. Main Outcomes
and Measures: The primary outcome was to quantitatively measure AK resolution,
and the secondary outcome was to assess pain associated with microneedle
pretreatment. Results: Thirty-three individuals were recruited and randomized to
either the 20-minute or the 10-minute incubation arm. Thirty-two participants
completed the study with a mean follow-up time of 34.5 days in the 20-minute
group, and 30.2 days in the 10-minute group. For the 20-minute incubation arm,
average AK clearance was 76% vs 58% on the sham side (P < .01), including 3
patients with complete clearance, although not statistically significant (P =
.25). Pain assessment on the visual analog scale (VAS) during blue light
illumination was not significantly different between the microneedle and sham
sides (0.7 and 0.4; P = .28), respectively. For the 10-minute incubation arm AK
clearance for the microneedle pretreated side was 43% compared with 38% on the
sham side (P = .66). Pain during the blue light exposure was not significantly
different between the microneedle and sham sides, 4.5 mm and 3.4 mm (P = .21),
respectively. Conclusions and Relevance: Photodynamic therapy with microneedle
pretreatment at a 20-minute ALA incubation time significantly improved AK
clearance with efficacy similar to that of a conventional 1-hour ALA incubation
time. The additional advantage to expedited treatment was that the procedure was
virtually painless. However, expedited exposure of a 10-minute ALA incubation
time did not reach significantly different AK clearance from the sham control.
Trial Registration: clinicaltrials.gov Identifier: NCT02594644.
PMID- 28514460
TI - Considering the Role of the Laparoscopic Adjustable Gastric Band: Do Not Throw
the Baby Out With the Bathwater.
PMID- 28514461
TI - Lessons to Be Learned From 22q11.2 Syndromes.
PMID- 28514462
TI - Lessons to be Learned From 22q2.11 Syndromes-Reply.
PMID- 28514464
TI - A Meta View on Meta-analyses.
PMID- 28514465
TI - Bicuspid Aortopathy-Reply.
PMID- 28514466
TI - How Microneedles Can Change Cutaneous Drug Delivery-Small Needles Make a Big
Difference.
PMID- 28514468
TI - Disseminated Erythematous Crusted and Pustular Plaques on the Trunk.
PMID- 28514467
TI - Novel Deceased Donor Perfusion Model for High-Fidelity Simulation in Vascular
Surgery.
PMID- 28514463
TI - Pediatric Psoriasis Comorbidity Screening Guidelines.
AB - Importance: Psoriasis is a complex inflammatory skin condition associated with
serious medical comorbidities in adults, including obesity, hypertension,
dyslipidemia, type 2 diabetes mellitus, psoriatic arthritis, nonalcoholic fatty
liver disease, depression, anxiety, and decreased quality of life. Because
psoriasis begins in childhood in almost one-third of patients, early
identification of risk may be critical to minimizing effects on future health.
Objective: To develop the first set of guidelines for comorbidity screening for
patients with pediatric psoriasis based on current evidence. Evidence Review: A
literature review was performed using PubMed from January 1999 through December
2015. Limiting the search to human studies published in English and removing
reviews and editorials produced 153 relevant manuscripts. An expert panel in
psoriasis, pediatric dermatology, pediatric rheumatology, pediatric
gastroenterology, pediatric endocrinology, and adult and pediatric cardiology
used the patient-centered Strength of Recommendation Taxonomy (SORT) method to
evaluate and grade the quality of evidence. Findings: Because of the limited
number of pediatric studies published on these topics, the strength of the
panel's recommendations is classified as SORT level C expert consensus
recommendations. The majority of recommendations coincide with those endorsed by
the American Academy of Pediatrics for the general pediatric patient but with
added attention to signs and symptoms of arthritis, depression, and anxiety. The
panel also identified key areas for further investigation. Conclusions and
Relevance: Patients with pediatric psoriasis should receive routine screening and
identification of risk factors for associated comorbidities. These guidelines are
relevant for all health care providers caring for patients with pediatric
psoriasis, including primary care clinicians, dermatologists, and pediatric
specialists. Because these are the first pediatric guidelines, re-review and
refinement will be necessary as studies further detail, and possibly stratify,
risk in affected children.
PMID- 28514471
TI - Addressing the Communication and Other Needs of Persons With Severe Disabilities
Through Engaged Interprofessional Teams: Introduction to a Clinical Forum.
AB - Purpose: Interprofessional collaborative practice (IPCP) is introduced as a
viable and preferred clinical methodology for speech-language pathologists and
others serving persons with severe disabilities. Contributions to this clinical
forum dedicated to IPCP and severe disabilities are described. Method: This
clinical focus article introduces IPCP and reviews literature specific to its
origins and effectiveness, defines severe disabilities, and proposes IPCP as a
vital tenet in effective communication-related and other service delivery for
this population. Conclusion: IPCP is supported as a recommended practice
methodology for speech-language pathologists and other team members providing
services to persons with severe disabilities.
PMID- 28514472
TI - The Trifocus Framework and Interprofessional Collaborative Practice in Severe
Disabilities.
AB - Purpose: Individuals with severe disabilities are a diverse group of learners
with complex communication needs. This article presents a synthesis of the
literature addressing the five strategies of the trifocus framework, with its
triadic structure of learner with disability, communication partner, and
environment. The application of interprofessional collaborative practice (IPCP)
to the implementation of trifocus framework communication strategies is
emphasized. Method: A literature search was conducted using Google Scholar and
EBSCO to identify literature and research studies on IPCP and communication
intervention for learners with severe disabilities, published 1994-2015, and then
organized within the trifocus framework. The trifocus strategies are enhancing
sensitivity, utilizing routines, increasing communication opportunities,
modifying the communication environment, and augmenting input. Studies that
included at least one participant with severe disabilities and their
communication partners were considered. A secondary search was then conducted by
reviewing the articles referenced in the original articles. Conclusion: Effective
IPCP in communication intervention considers the learner's characteristics, the
knowledge and skills required of communication partners, and effective
environmental arrangements to support communication. Future research should
include clear participant descriptions, documentation of fidelity measures, and
evidence of generalization to support professionals to know when findings are
relevant to the individuals they serve.
PMID- 28514470
TI - Noncontact spirometry with a webcam.
AB - We present an imaging-based method for noncontact spirometry. The method tracks
the subtle respiratory-induced shoulder movement of a subject, builds a
calibration curve, and determines the flow-volume spirometry curve and vital
respiratory parameters, including forced expiratory volume in the first second,
forced vital capacity, and peak expiratory flow rate. We validate the accuracy of
the method by comparing the data with those simultaneously recorded with a gold
standard reference method and examine the reliability of the noncontact
spirometry with a pilot study including 16 subjects. This work demonstrates that
the noncontact method can provide accurate and reliable spirometry tests with a
webcam. Compared to the traditional spirometers, the present noncontact
spirometry does not require using a spirometer, breathing into a mouthpiece, or
wearing a nose clip, thus making spirometry test more easily accessible for the
growing population of asthma and chronic obstructive pulmonary diseases.
PMID- 28514469
TI - Association of Very Low-Volume Practice With Vascular Surgery Outcomes in New
York.
AB - Importance: Little research has focused on very low-volume surgery, especially in
the context of decreasing vascular surgery volume with the adoption of
endovascular procedures. Objective: To investigate the existence and outcomes of
open abdominal aortic aneurysm repair (OAR) and carotid endarterectomy (CEA)
performed by very low-volume surgeons in New York. Design, Settings, and
Participants: This cohort study examined inpatient data of patients undergoing
elective OAR or CEA from 2000 to 2014 from all New York hospitals. Exposures:
Surgeons who performed 1 or less designated procedure per year on average were
considered very low volume, as opposed to higher-volume surgeons. Main Outcomes
and Measures: Temporal trends of the existence of very low-volume practice were
evaluated. Hierarchical logistic regression was used to compare in-hospital
outcomes and health care resource use between patients treated by very low-volume
surgeons and higher-volume surgeons for both OAR and CEA, adjusting for patient,
surgeon, and hospital characteristics. Results: There were 8781 OAR procedures
and 68 896 CEA procedures included in the study. The mean (SD) patient age was
71.7 (8.4) years for OAR and 71.5 (9.1) years for CEA. A total of 614 surgeons
performed OAR and 1071 performed CEA in New York during the study period. Of
these, 318 (51.8%) and 512 (47.8%), respectively, were very low-volume surgeons.
Very low-volume surgeons were less likely to be vascular surgeons. The number and
proportion of very low-volume surgeons decreased over years. Compared with
patients treated by higher-volume surgeons, those treated by very low-volume
surgeons were more likely to have higher in-hospital mortality (odds ratio [OR],
2.09; 95% CI, 1.41-3.08) following OAR and higher risks of postoperative
myocardial infarction (OR, 1.83; 95% CI, 1.03-3.26) and stroke (OR, 1.78; 95% CI,
1.21-2.62) following CEA. Patients treated by very low-volume surgeons also had
greater health care resource use following both surgeries, including prolonged
length of stay (OR, 1.37; 95% CI, 1.11-1.70) following OAR as well as higher
charges (OR, 1.28; 95% CI, 1.01-1.62) and increased 30-day readmission (OR, 1.30;
95% CI 1.04-1.62) following CEA. Conclusions and Relevance: The OAR and CEA
procedures performed by very low-volume surgeons resulted in worse postoperative
outcomes and greater lengths of stay. Although the percentage of very low-volume
surgeons declined from 2000 to 2014, it remains concerning, given ready access to
higher-volume surgeons. Future research is needed to understand the existence of
this practice pattern in other surgical fields. Efforts to eliminate this
practice pattern are warranted to ensure high-quality care for all patients.
PMID- 28514473
TI - Effective Team Practices: Interprofessional Contributions to Communication Issues
With a Parent's Perspective.
AB - Purpose: This clinical focus article contains a detailed description of how to
build effective teams that use interprofessional collaborative practice (IPCP)
with special-education professionals, speech-language pathologists, and families
of children with severe disabilities. Method: This clinical focus article
provides information on using the essential elements of team building and IPCP to
provide quality care to families who have children with severe disabilities. The
6 essential elements for team building are described, with suggestions for
including families in each: goal-setting, roles and responsibilities, effective
and efficient process, communication and interpersonal relationships,
collaborative problem solving, and evaluation. The 4 competency domains of IPCP
are embedded into each of the team-building elements to demonstrate how teams can
implement IPCP. Results: A case study illustrates the difficulty one parent
experienced working with a team across the 6 essential team-building elements
when seeking communication services for her child with severe disabilities.
Conclusions: Building teams with IPCP can be effective for including families and
creating high-quality outcomes for individuals with severe disabilities.
PMID- 28514475
TI - Cotreatment as a Vehicle for Interprofessional Collaborative Practice: Physical
Therapists and Speech-Language Pathologists Collaborating in the Care of Children
With Severe Disabilities.
AB - Purpose: This article defines interprofessional collaborative practice and links
its key features with accepted practice conceptualizations of physical therapy.
Cotreatment with speech-language pathology is described as a vehicle for
interprofessional collaborative practice for children with severe disabilities.
Method: The article reviews the International Classification of Functioning,
Disability, and Health (WHO, 2015) and the Hypothesis-Oriented Algorithm for
Clinicians II (Rothstein, Echternach, & Riddle, 2003) as existing service
delivery frameworks in physical therapy and discusses how interprofessional
collaborative practice between speech-language pathologists and physical
therapists can be useful within these practice guidelines. Results: A case
illustration featuring interprofessional collaborative practice during
cotreatment for a child with severe disabilities through physical therapy and
speech-language pathology showed more seamless care and better progress in the
pursuit of three main goals: physical movement, communication of needs, and
participation in classroom activities. Conclusions: Interprofessional
collaborative practice is supported as a recommended practice methodology for
physical therapists and speech-language pathologists serving persons with severe
disabilities.
PMID- 28514474
TI - Comprehensive Literacy Instruction, Interprofessional Collaborative Practice, and
Students With Severe Disabilities.
AB - Purpose: The purpose of this clinical focus article is to briefly describe
comprehensive emergent and conventional literacy instruction for students with
severe disabilities. Specific attention is given to interprofessional
collaborative practice and the roles of team members in planning and delivering
instruction. Method: A rationale for the delivery of comprehensive instruction
that balances skill and meaning emphases is provided with reference to new
college and career readiness standards, the literature on literacy acquisition
for students without disabilities, and, when possible, the literature on literacy
acquisition for students with severe disabilities. Specific instructional
approaches are presented to demonstrate how teams can actively engage students
with severe disabilities in instruction that is collaborative, participatory, and
interactive. Results/Conclusions: Successful provision of comprehensive literacy
instruction that allows students with severe disabilities to achieve conventional
literacy takes time and the efforts of a collaborative interprofessional team.
Speech-language pathologists play a critical role on these teams as they ensure
that students with severe disabilities have the language and communication
supports they need to be successful.
PMID- 28514476
TI - Mary's Case: An Illustration of Interprofessional Collaborative Practice for a
Child With Severe Disabilities.
AB - Purpose: The principles of interprofessional collaborative practice (IPCP) are
illustrated through the case of Mary, a child with severe disabilities. Method:
Mary's experiences from early childhood to young adulthood are highlighted by
both optimal and less-than-ideal examples of clinical services and collaborative
practice. The range of collaboration illustrates potential variations in service
delivery. Thematic comments and resources are provided by professionals
experienced with and committed to IPCP who represent the following four
disciplines: occupational therapy, physical therapy, special education, and
speech-language pathology. Conclusions: Although potentially challenging, IPCP is
a dynamic practice methodology appropriate for speech-language pathologists and
others serving persons with severe disabilities.
PMID- 28514481
TI - Outside the Door.
PMID- 28514478
TI - Trajectories of Depressive Symptoms Before Diagnosis of Dementia: A 28-Year
Follow-up Study.
AB - Importance: Neuropsychiatric symptoms, depressive symptoms in particular, are
common in patients with dementia but whether depressive symptoms in adulthood
increases the risk for dementia remains the subject of debate. Objective: To
characterize the trajectory of depressive symptoms over 28 years prior to
dementia diagnosis to determine whether depressive symptoms carry risk for
dementia. Design, Setting, and Participants: Up to 10 308 persons, aged 35 to 55
years, were recruited to the Whitehall II cohort study in 1985, with the end of
follow-up in 2015. Data analysis for this study in a UK general community was
conducted from October to December 2016. Exposures: Depressive symptoms assessed
on 9 occasions between 1985 and 2012 using the General Health Questionnaire. Main
Outcomes and Measures: Incidence of dementia (n = 322) between 1985 and 2015.
Results: Of the 10 189 persons included in the study, 6838 were men (67%) and
3351 were women (33%). Those reporting depressive symptoms in 1985 (mean follow
up, 27 years) did not have significantly increased risk for dementia (hazard
ratio [HR], 1.21; 95% CI, 0.95-1.54) in Cox regression adjusted for
sociodemographic covariates, health behaviors, and chronic conditions. However,
those with depressive symptoms in 2003 (mean follow-up, 11 years) had an
increased risk (HR, 1.72; 95% CI, 1.21-2.44). Those with chronic/recurring
depressive symptoms (>=2 of 3 occasions) in the early study phase (mean follow
up, 22 years) did not have excess risk (HR, 1.02; 95% CI, 0.72-1.44) but those
with chronic/recurring symptoms in the late phase (mean follow-up, 11 years) did
have higher risk for dementia (HR, 1.67; 95% CI, 1.11-2.49). Analysis of
retrospective depressive trajectories over 28 years, using mixed models and a
backward time scale, shows that in those with dementia, differences in depressive
symptoms compared with those without dementia became apparent 11 years
(difference, 0.61; 95% CI, 0.09-1.13; P = .02) before dementia diagnosis and
became more than 9 times larger at the year of diagnosis (difference, 5.81; 95%
CI, 4.81-6.81; P < .001). Conclusions and Relevance: Depressive symptoms in the
early phase of the study corresponding to midlife, even when chronic/recurring,
do not increase the risk for dementia. Along with our analysis of depressive
trajectories over 28 years, these results suggest that depressive symptoms are a
prodromal feature of dementia or that the 2 share common causes. The findings do
not support the hypothesis that depressive symptoms increase the risk for
dementia.
PMID- 28514482
TI - Breast Cancer Genetic Testing Among African Patients With Breast Cancer:
Deoxyribonucleic Acid Extraction From Tumor Tissue and International
Multidisciplinary Partnerships.
PMID- 28514485
TI - Occurrence of Acute Cerebellar Syndrome After Topical Application of
Fluorouracil.
PMID- 28514486
TI - Efficacy of 42 Pharmacologic Cotreatment Strategies Added to Antipsychotic
Monotherapy in Schizophrenia: Systematic Overview and Quality Appraisal of the
Meta-analytic Evidence.
AB - Importance: Limited treatment responses in schizophrenia prompted the testing of
combining an antipsychotic drug treatment with a second psychotropic medication.
A comprehensive evaluation of the efficacy of multiple medication combinations is
missing. Objective: To summarize and compare the meta-analytically determined
efficacy of pharmacologic combination strategies of antipsychotic drugs in adults
with schizophrenia. Data Sources: Systematic search of PubMed and PsycInfo until
May 13, 2016. Study Selection: Meta-analyses of randomized clinical trials
comparing the efficacy of antipsychotic drugs combined with other antipsychotic
or nonantipsychotic medications vs placebos or antipsychotic monotherapy among
adults with schizophrenia. Data Extraction and Synthesis: Independent reviewers
extracted the data and assessed the quality of the methods of the included meta
analyses using A Measurement Tool to Assess Systematic Reviews (AMSTAR), adding 6
new items to rate their quality. Effect sizes, expressed as standardized mean
difference /Hedges g or risk ratio, were compared separately for combinations
with any antipsychotic drug and for combinations with clozapine. Main Outcomes
and Measures: The primary outcome was total symptom reduction. Secondary outcomes
included positive and negative symptoms, treatment recommendations by authors,
study-defined inefficacies, cognitive and depressive symptoms, discontinuation of
treatment because of any cause, and inefficacies or intolerabilities. Results: Of
3397 publications, 29 meta-analyses testing 42 combination strategies in 381
individual trials and among 19 833 participants were included. For total symptom
reductions, 32 strategies that augmented any antipsychotic drug and 5 strategies
that augmented clozapine were examined. Fourteen combination treatments
outperformed controls (standard mean difference/Hedges g, -1.27 [95% CI, -2.35 to
-0.19] to -0.23 [95% CI, -0.44 to -0.02]; P = .05). No combination strategies
with clozapine outperformed controls. The quality of the methods of the meta
analyses was generally high (mean score, 9 of a maximum score of 11) but the
quality of the meta-analyzed studies was low (mean score, 2.8 of a maximum score
of 8). Treatment recommendations correlated with the effect size (correlation
coefficient, 0.22; 95% CI, 0.35-0.10; P < .001), yet effect sizes were inversely
correlated with study quality (correlation coefficient, -0.06; 95% CI, 0.01 to
0.12; P = .02). Conclusions and Relevance: Meta-analyses of 21 interventions
fully or partially recommended their use, with recommendations being positively
correlated with the effect sizes of the pooled intervention. However, the effect
sizes were inversely correlated with meta-analyzed study quality, reducing
confidence in these recommendations. Higher-quality trials and patient-based meta
analyses are needed to determine whether subpopulations might benefit from
combination treatment, as no single strategy can be recommended for patients with
schizophrenia based on the current meta-analytic literature.
PMID- 28514488
TI - Optimal vs Feasible Volume Thresholds in Vascular Surgery.
PMID- 28514489
TI - Nerve Conduction Studies for Carpal Tunnel Syndrome: Gold Standard or Unnecessary
Evil?
PMID- 28514487
TI - Reoperation and Medicare Expenditures After Laparoscopic Gastric Band Surgery.
AB - Importance: Following the US Food and Drug Administration approval for
laparoscopic gastric band surgery in 2001, as many as 96 000 devices have been
placed annually. The reported rates of reoperation range from 4% to 60% in short
term studies; however, to our knowledge, few long-term population-level data on
outcomes or expenditures are known. Objective: To describe the rate of device
related reoperations occurring after laparoscopic gastric band surgery as well as
the associated payments in a longitudinal national cohort. Design, Settings, and
Participants: This retrospective review of 25 042 Medicare beneficiaries who
underwent gastric band placement between 2006 and 2013 identifies gastric band
related reoperations, including device removal, device replacement, or revision
to a different bariatric procedure (eg, a gastric bypass or sleeve gastrectomy).
The rates of reoperation were risk adjusted using a multivariable logistic
regression model that included patient age, sex, race/ethnicity, Elixhauser
comorbidities, and the year that the operation was performed. Main Outcomes and
Measures: Rate of device-related reoperation nationally and across individual
hospital referral regions. Thirty-day total episode Medicare payments to
hospitals for the index operation and any subsequent reoperations. Results: Of
the 25 042 patients who underwent gastric band placement, 20 687 (82.61%) were
white, 18 143 (72.45%) were women, and the mean age was 57.56 years. Patients
(mean age, 57.5; 76.2% women) requiring reoperation had lower rates of
hypertension (64.9% vs 73.4%; P < .001) and diabetes (40.4% vs 44.6%; P < .001)
and were more likely to have their index operation at a for-profit hospital
(34.6% vs 22.0%; P < .001). With an average of 4.5-year follow-up, 4636 patients
(18.5%) underwent 17 539 reoperations (an average of 3.8 procedures/patient).
Hospital referral regions demonstrated a 2.9-fold variation in risk- and
reliability-adjusted rates of reoperation (lower quartile average, 13.3%; upper
quartile average, 39.1%). During the study period, Medicare paid $470 million for
laparoscopic gastric band associated procedures, of which $224 million (47.6%) of
the payments were for reoperations. From 2006 to 2013, the proportion of payments
from Medicare for reoperations increased from 16.4% to 77.3% of their annual
spending on the gastric band device. Conclusions and Relevance: Among Medicare
beneficiaries undergoing gastric band surgery, device-related reoperation was
common, costly, and varied widely across hospital referral regions. These
findings suggest that payers should reconsider their coverage of the gastric band
device.
PMID- 28514490
TI - Brain ultrasound rehearsal before surgery: A pilot cadaver study.
AB - It has been shown that brain ultrasonography (US) is an efficient tool for
improving three-dimensional (3D) spatial orientation during neurosurgical
interventions. However, it necessitates specific training as it is highly
operator-dependent. To date, neurosurgeons have relied solely on intraoperative
practice to improve their mastery of brain US; this has obvious limitations.
Herein, we consider whether a study of brain US on human cadavers could enable a
training platform for neurosurgeons and residents to be developed. Standard two
dimensional (2D) brain US was performed on two human cadavers (one fresh-frozen
and one Thiel-prepared) through left frontoparietal, left frontal, right
temporal, and left parietal craniotomies. US workflow and image quality were
assessed in both preparations. It was possible to assess US in both cadaver
preparations; however, the specimen prepared with Thiel-fixation performed
better, with superior image quality and specimen usability at room temperature.
US images were obtainable through all surgical corridors with the main
intracranial anatomical landmarks easily identifiable. US of cadaveric brains is
feasible and delivers good quality results. This technique could allow
neurosurgeons to develop the expertise required for a successful clinical
application preoperatively. Clin. Anat. 30:1017-1023, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28514492
TI - Ordering by the numbers in anatomy and by letters Too.
AB - Here, new rules of Latin anatomical nomenclature are proposed to deal with cases
not covered by existing or other recommended rules. Determiners (e.g., numerals,
letters, alphanumeric strings, and Latin names of Greek letters) should follow
the noun they specify or limit, just as it is recommended that adjectives should
follow the noun they modify. In general, Roman numerals, Latin letters, and Latin
names of Greek letters are preferable to Arabic numerals and Greek letters in
Latin anatomical terms. It is also noted that the word typus (type) appears to be
superfluous and unnecessary in the Latin anatomical nomenclature. Clin. Anat.
30:700-702, 2017. (c) 2017Wiley Periodicals, Inc.
PMID- 28514491
TI - 3D image-based morphometric analysis of the scapular neck length in subjects
undergoing reverse shoulder arthroplasty.
AB - Scapular notching after RSA may, in part, be related to a patient's scapular
morphology. The purpose of this study was to develop a novel 3 D measurement
technique to describe infraglenoid tubercle morphometry. We hypothesize that the
parameters describing infraglenoid tubercle would be normally distributed and
would correlate with individual's demographics and glenoid morphometry. A group
of 110 subjects treated with RSA were evaluated. Scapular geometry was obtained
from pre-operative CT scans. The scapular neck length was defined in anterior and
posterior view as the orthogonal distance between the glenoid surface and (a) the
point of most significant change of curvature on lateral pillar; (b) the most
lateral portion of the infraglenoid tubercle. Scapular neck angle, maximum
anatomical adduction angle, glenoid width, height and version were also measured.
Scapular neck length measured in the anterior and posterior view were normally
distributed with mean values of 17.6 +/- 2.8 mm and 7.9 +/- 2.5 mm, respectively.
Scapular neck angle was on average 112.4 +/- 10.6 degrees and maximal adduction
angle was 17.6 +/- 2.8 degrees . No significant associations between infraglenoid
tubercle morphometric parameters, demographic, glenoid size or version were
identified. Improved understanding of the patient-specific risk factors for
scapular notching will help surgeons with pre-surgical planning and implant
selection. Parametrization of the infraglenoid tubercle presented in this study
showed normal distribution in the population unrelated to gender, side or
demographics. The size of the infraglenoid tubercle is a unique trait, pre
operative evaluation of the scapular neck should be always warranted to decrease
the incidence of post-operative notching. Clin. Anat. 31:43-55, 2018. (c) 2017
Wiley Periodicals, Inc.
PMID- 28514493
TI - The Narrow Road to the Deep Past: In Search of the Chemistry of the Origin of
Life.
AB - The sequence of events that gave rise to the first life on our planet took place
in the Earth's deep past, seemingly forever beyond our reach. Perhaps for that
very reason the idea of reconstructing our ancient story is tantalizing, almost
irresistible. Understanding the processes that led to synthesis of the chemical
building blocks of biology and the ways in which these molecules self-assembled
into cells that could grow, divide and evolve, nurtured by a rich and complex
environment, seems at times insurmountably difficult. And yet, to my own
surprise, simple experiments have revealed robust processes that could have
driven the growth and division of primitive cell membranes. The nonenzymatic
replication of RNA is more complicated and less well understood, but here too
significant progress has come from surprising developments. Even our efforts to
combine replicating compartments and genetic materials into a full protocell
model have moved forward in unexpected ways. Fortunately, many challenges remain
before we will be close to a full understanding of the origin of life, so the
future of research in this field is brighter than ever!
PMID- 28514494
TI - Covalent Protein Labeling by SpyTag-SpyCatcher in Fixed Cells for Super
Resolution Microscopy.
AB - Labeling proteins with high specificity and efficiency is a fundamental
prerequisite for microscopic visualization of subcellular protein structures and
interactions. Although the comparatively small size of epitope tags makes them
less perturbative to fusion proteins, they require the use of large antibodies
that often limit probe accessibility and effective resolution. Here we use the
covalent SpyTag-SpyCatcher system as an epitope-like tag for fluorescent labeling
of intracellular proteins in fixed cells for both conventional and super
resolution microscopy. We also applied this method to endogenous proteins by gene
editing, demonstrating its high labeling efficiency and capability for isoform
specific labeling.
PMID- 28514495
TI - Protective effects of dioscin against cisplatin-induced nephrotoxicity via the
microRNA-34a/sirtuin 1 signalling pathway.
AB - BACKGROUND AND PURPOSE: Dioscin exhibits a range of pharmacological actions but
little is known of its effects on cisplatin (CDDP)-induced nephrotoxicity. Here,
we have assessed the effects and the possible mechanisms of dioscin against CDDP
induced nephrotoxicity. EXPERIMENTAL APPROACH: We used an in vivo model of CDDP
induced nephrotoxicity in rats and mice and, in vitro, cultures of NRK-52E and HK
2 cells. The dual luciferase reporter assay was used to demonstrate modulation,
by dioscin, of the targeting of sirtuin 1 (Sirt1) by microRNA (miR)-34a.
Molecular docking assays were used to analyse the effects of dioscin with Sirt1,
Keap1 and NF-kappaB. KEY RESULTS: Dioscin attenuated cell damage in vitro and
decreased renal injury in rats and mice, treated with CDDP. In terms of
mechanisms, dioscin reversed CDDP-induced up-regulation of miR-34a and thus up
regulated Sirt1 levels. In addition, dioscin altered levels of haem oxygenase 1,
glutathione-cysteine ligase subunits (GCLC, GCLM) and Keap1, along with increased
nuclear translocation of Nrf2, thus decreasing oxidative stress. Also, dioscin
affected levels of AP-1, COX-2, HMGB1, IkappaB-alpha, IL-1beta, IL-6 and TNF
alpha and decreased the ratio of acetylated NF-kappaB and normal NF-kappaB, to
suppress inflammation. From molecular docking assays, dioscin directly bound to
Sirt1, Keap1 and NF-kappaBp65 by hydrogen bonding and/or hydrophobic
interactions. CONCLUSIONS AND IMPLICATIONS: Our results have linked CDDP-induced
nephrotoxicity and the miR-34a/Sirt1 signalling pathway, which was modulated by
dioscin. This natural product could be developed as a new candidate to alleviate
CDDP-induced renal injury.
PMID- 28514496
TI - A reappraisal of pediatric thoracic surface anatomy.
AB - Accurate knowledge of surface anatomy is fundamental to safe clinical practice. A
paucity of evidence in the literature regarding thoracic surface anatomy in
children was identified. The associations between surface landmarks and internal
structures were meticulously analyzed by reviewing high quality computed
tomography (CT) images of 77 children aged from four days to 12 years. The
results confirmed that the sternal angle is an accurate surface landmark for the
azygos-superior vena cava junction in a plane through to the level of upper T4
from birth to age four, and to lower T4 in older children. The concavity of the
aortic arch was slightly below this plane and the tracheal and pulmonary artery
bifurcations were even lower. The cardiac apex was typically at the 5th
intercostal space (ICS) from birth to age four, at the 4th ICS and 5th rib in 4
12 year olds, and close to the midclavicular line at all ages. The lower border
of the diaphragm was at the level of the 6th or 7th rib at the midclavicular
line, the 7th ICS and 8th rib at the midaxillary line, and the 11th thoracic
vertebra posteriorly. The domes of the diaphragm were generally flatter and lower
in children, typically only one rib level higher than its anterior level at the
midclavicular line. Diaphragm apertures were most commonly around the level of
T9, T10, and T11 for the IVC, esophagus and aorta, respectively. This is the
first study to provide an evidence-base for thoracic surface anatomy in children.
Clin. Anat. 30:788-794, 2017. (c) 2017Wiley Periodicals, Inc.
PMID- 28514497
TI - Does mutational analysis influence the management of differentiated thyroid
cancers?
PMID- 28514498
TI - Decreased bed rest post-percutaneous coronary intervention with a 7-French
arterial sheath and its effects on vascular complications.
AB - AIMS AND OBJECTIVES: To compare the incidence of femoral access puncture site
complications in the control group, who underwent 6 hr of bed rest, with patients
in the case group, who underwent 4 hr of bed rest. BACKGROUND: The ideal bed rest
length after percutaneous coronary intervention with a 7-French arterial sheath
has been investigated by nursing practice. However, in this larger-sheath-size
group, best practices have not been determined, and bed rest time continues to
vary markedly among institutions. DESIGN: Retrospective study. METHODS: Data were
retrieved from the National Cardiovascular Data Registry and electronic health
records in this retrospective study. Sample size was 401 patients: 152 case
patients with 4-hr bed rest and 249 controls with 6-hr bed rest. Case group data
were obtained from 20 May 2013-31 December 2014; and control group data, 15 June
2011-20 May 2013. RESULTS: National Cardiovascular Data Registry event rates were
generally low in both groups: Only three patients in each group had a bleeding
event within 72 hr (2% vs. 1%) and no patient and only two controls had
arteriovenous fistula (0% vs. 1%). Complications documented in the electronic
health records with institutional femoral access puncture site complication
definitions identified bleeding at the access site in eight case patients (5%)
and nine controls (4%). Haematoma at the access site occurred in 21 case patients
(14%) and 25 controls (10%). CONCLUSIONS: The practice change of decreasing bed
rest from 6-4 hr for patients with 7-French arterial sheaths post-percutaneous
coronary intervention was associated with no significant change in femoral access
puncture site complications in either National Cardiovascular Data Registry data
or institutional electronic health records data. RELEVANCE TO CLINICAL PRACTICE:
This introduces expanded evidence of safety in decreasing bed rest length in
larger (7-French) arterial sheaths post-percutaneous coronary intervention.
PMID- 28514499
TI - Surface anatomy of major anatomical landmarks of the neck in an adult population:
A Ct Evaluation of Vertebral Level.
AB - To compare the projectional surface anatomy of healthy individuals in an adult
population with those with a thyroid mass, using computed tomography (CT).
Sixteen slice CT images of 101 individuals were analyzed using a 32-bit Radiant
DICOM viewer to establish the relationships among major anatomical landmarks in
the neck and their vertebral levels. The structures investigated included: hard
palate (HP), hyoid bone (HB) including body and lesser horns, soft palate (SP),
thyroid gland (TG) (both superior and inferior poles), thyroid gland
anteroposterior (APD) and superoinferior (SID) diameters, thyroid isthmus (TI)
superoinferior dimension, epiglottis, vertebral arteries (right and left), and
both right and left parotid glands (superior and inferior extents). The vertebral
levels noted most frequently were: body of hyoid bone (C4, 42.71%); lesser horns
of hyoid bone (C3, 36.46%); thyroid gland superior pole (C6, 31.25%); and thyroid
gland inferior pole (T2, 30.2%). TG-ID, TG-APD, and TG-SID were not significantly
different between males and females in the healthy group; however, there was a
significant gender difference in thyroid gland inferior diameter in the pathology
group [males 2.16(+/-1.16) vs. females 3.37(+/-1.30), P = 0.01, paired sample t
test]. Further studies are needed to determine whether neck pathology in those
with a thyroid mass affects the dimensions of the thyroid gland. Moreover, the
surface anatomy of the neck should be revisited using modern imaging techniques
to address inconsistencies in anatomy and clinical reference texts. Clin. Anat.
30:781-787, 2017. (c) 2017Wiley Periodicals, Inc.
PMID- 28514500
TI - Histology of the distal dural ring.
AB - The distal dural ring (DDR) is a conserved intracranial anatomic structure
marking the boundary point at which the internal carotid artery (ICA) exits the
cavernous sinus (CS) and enters the subarachnoid space. Although the CS has been
well described in a range of anatomic studies, to our knowledge no prior study
has analyzed the histologic relationship between the ICA and DDR.
Correspondingly, our objective was to assess the relationship of the DDR to the
ICA and determine whether the DDR can be dissected from the ICA and thus divided,
or can only be circumferentially trimmed around the artery. The authors examined
ten fresh-frozen, adult cadaveric specimens. A standard frontotemporal
craniotomy, orbito-optic osteotomy, and extradural anterior clinoidectomy was
performed bilaterally. The cavernous ICA, DDR, and supraclinoid ICA were
harvested as an en bloc specimen. Specimens formalin-fixed and paraffin-embedded
prior to routine histochemical staining with hematoxylin and eosin and Masson
trichrome. In all specimens, marked microscopic investment of the DDR throughout
the ICA adventitia was noted. Dural collagen fibers extensively permeated the
arterial layers superficial to the muscularis propria, with no evidence of a
clear separation between the DDR and arterial adventitia. Histologic analysis
suggests that the ICA and DDR are highly interrelated, continuous structures, and
therefore attempted intraoperative dissection between these structures may carry
an elevated risk of injury to the ICA. We correspondingly recommend careful
circumferential trimming of the DDR in lieu of direct dissection in cases
requiring mobilization of the clinoidal ICA. Clin. Anat. 30:742-746, 2017. (c)
2017Wiley Periodicals, Inc.
PMID- 28514501
TI - Intra-articular capacity of the elbow joint.
AB - The intra-articular capacity of the elbow joint is reported to be 23 +/- 4 ml on
cadaveric elbows. During years, this value was the standard. The aim of this
observational study was to reanalyze the volume of the elbow joint on live
patients. Measurement of the intra-articular capacity and pressure of the elbow
joint was performed on 30 patients (mean age: 43.8 years) undergoing elbow
arthroscopy. Intra-articular capacity was recorded when the elbow moved to the
maximum lose packed position and/or when there was a sudden drop in pressure,
indicating a capsular rupture (maximum capacity). Indications for arthroscopy
were loose bodies, osteoarthritis, synovitis, radial head resection, and lateral
collateral ligament repair. Mean intra-articular capacity and pressure were 35.8
ml and 557.5 mm Hg, respectively. Mean maximal capacity was 40.5 ml. We conclude
that the intra-articular capacity of the elbow joint is substantially greater
than reported in previous studies. Clin. Anat. 30:795-798, 2017. (c) 2017Wiley
Periodicals, Inc.
PMID- 28514503
TI - Slicing Diamond for More sp3 Group 14 Allotropes Ranging from Direct Bandgaps to
Poor Metals.
AB - Considerable interest in novel Si allotropes has led to intense investigation of
tetrahedral framework structures during the last years. Recently, a guide to
deriving sp3 -Si allotropes from atom slabs of the diamond structure enabled a
systematic deduction of several low-density modifications. Some of the Si
networks were recognized as experimentally known frameworks, that is, so-called
"chemi-inspired" structures. Herein we present nine novel Si networks obtained by
modifying three-atom-thick slabs of a cubic diamond structure after smooth
distortion by applying the same construction kit. Analysis of the structure
property relationships of these frameworks by using quantum-chemical methods
shows that several of them possess direct bandgaps in the range suitable for
light conversion. The construction kit was also applied to higher group 14
homologues Ge and Sn, and revealed interesting differences in the band structures
and relative energies of the homologues. A new modification of Sn was identified
as a poor metal, which denoted significant covalent-bond characteristics.
PMID- 28514504
TI - An anatomical variation of the eminentia hypothenaris.
PMID- 28514502
TI - Structural and functional characteristics of oestrogen receptor beta splice
variants: Implications for the ageing brain.
AB - Oestrogen receptor (ER)beta is a multifunctional nuclear receptor that mediates
the actions of oestrogenic compounds. Despite its well defined role in mediating
the actions of oestrogens, a substantial body of evidence demonstrates that
ERbeta has a broad range of physiological functions independent of those normally
attributed to oestrogen signalling. These functions can partly be achieved by the
activity of several alternatively spliced isoforms that have been identified for
ERbeta. This short review describes structural differences between the ERbeta
splice variants that are known to be translated into proteins. Moreover, we
discuss how these alternative structures contribute to functional differences in
the context of both healthy and pathological conditions. Our review also
describes the principal factors that regulate alternative RNA splicing. The
alternatively spliced isoforms of ERbeta are differentially expressed according
to brain region, age and hormonal milieu, emphasising the likelihood that there
are precise cell-specific mechanisms regulating ERbeta alternative splicing.
However, despite these correlative data, the molecular factors regulating
alternative ERbeta splicing in the brain remain unknown. We also review the basic
mechanisms that regulate alternative RNA splicing and use that framework to make
logical predictions about ERbeta alternative splicing in the brain.
PMID- 28514505
TI - The trajectory of experience of critical care nurses in providing end-of-life
care: A qualitative descriptive study.
AB - AIMS AND OBJECTIVES: To understand the perceptions of critical care nurses
towards providing end-of-life care. BACKGROUND: There has been an increasing
interest in end-of-life care in the critical care setting. In Singapore,
approximately half of deaths in the hospital occur during critical care. While
nurses are well positioned to provide end-of-life care to patients and their
family members, they faced barriers to providing end-of-life care. Also,
providing end-of-life care has profound positive and negative psychological
effects on nurses, with the latter being more prominent. DESIGN: Qualitative
descriptive design. METHOD: Data collection was performed in a medical intensive
care unit of a public tertiary hospital in Singapore. Ten registered nurses were
purposively sampled and interviewed individually using a semi-structured
interview guide. A codebook was developed to guide coding, and data were
thematically analysed. Rigour was maintained. RESULTS: Nurses went through a
trajectory of experience. They experienced the culture of care and developed
dissatisfaction with it. The tension shaped their perception and meaning of life
and death, and they developed mechanisms to reach resolution. CONCLUSION: This
study provides insight on nurses' perception as a trajectory of experience and
raised several implications on clinical practice, policy and research. There is a
need to alleviate the tension nurses face and to facilitate coming to terms with
the tension by improving the culture of care and supporting nurses. RELEVANCE TO
CLINICAL PRACTICE: Nurses could be involved more in decision-making and empowered
to start end-of-life care conversations within the team and with family members.
Communication with family members and between nurses and doctors could be
improved. Support for nurses providing end-of-life care could be enhanced through
promoting social networks, education and bereavement support. Further research is
needed to explore ways to support and empower nurses to provide end-of-life care
in critical care.
PMID- 28514507
TI - Hydrogen Bonds Involving Cavity NH Protons Drives Supramolecular Oligomerization
of Amido-Corroles.
AB - trans-A2 B-Corroles with amide substituents at different positions versus the
macrocyclic core have been synthesized. Their self-organizing properties have
been comprehensively evaluated both in solid-state and in solution. The rigid
arrangement of the amide functionality with the corrole ring led to the formation
of strong intramolecular interactions and precluded intermolecular interactions.
Replacement of sterically hindered C6 F5 substituents at positions 5 and 15 with
smaller electron-withdrawing CO2 Me groups resulted in significant changes in the
self-assembly pattern. With these substituents, tetramers formed in a crystalline
state, in which one of the H-pyrrole subunits is out of the corrole plane. This
allows the N-H group to form a hydrogen bond with a neighboring carbonyl group of
the n-butyl amide fragment. DOSY NMR studies showed that amido-corroles bearing
the OCH2 CONHnBu motif formed dimers in millimolar solutions in nonpolar solvents
and the dimers existed in equilibrium with monomers. However, the corroles
possessing meso-ester groups did not form dimers in polar tetrahydrofuran.
Comprehensive optical studies allowed the absorption and emission features of the
monomer corroles to be characterized in dilute solutions.
PMID- 28514506
TI - Human Adipose-Derived Mesenchymal Stem Cell-Secreted CXCL1 and CXCL8 Facilitate
Breast Tumor Growth By Promoting Angiogenesis.
AB - Autologous adipose tissue or adipose tissue with additive adipose-derived
mesenchymal stem cells (ADSCs) is used in the breast reconstruction of breast
cancer patients who undergo mastectomy. ADSCs play an important role in the
angiogenesis and adipogenesis, which make it much better than other materials.
However, ADSCs may promote residual tumor cells to proliferate or metastasize,
and the mechanism is still not fully understood. In this study, we demonstrated
that human ADSCs (hADSCs) could facilitate tumor cells growth after co-injection
with MCF7 and ZR-75-30 breast cancer cells (BCCs) by promoting angiogenesis, but
hADSCs showed limited effect on the growth of MDA-MB-231 BCCs. Intriguingly,
compared with ZR-75-30 tumor cells, MCF7 tumor cells were more potentially
promoted by hADSCs in the aspects of angiogenesis and proliferation. Consistent
with this, cytokine and angiogenesis array analyses showed that after co
injection with hADSCs, the CXCL1 and CXCL8 concentration were significantly
increased in MCF7 tumor, but only moderately increased in ZR-75-30 tumor and did
not increase in MDA-MB-231 tumor. Furthermore, we found that CXCL1/8 were mainly
derived from hADSCs and could increase the migration and tube formation of human
umbilical vein endothelial cells (HUVECs) by signaling via their receptors CXCR1
and CXCR2. A CXCR1/2-specific antagonist (SCH527123) attenuated the angiogenesis
and tumor growth in vivo. Our findings suggest that CXCL1/8 secreted by hADSCs
could promote breast cancer angiogenesis and therefore provide better
understanding of safety concerns regarding the clinical application of hADSCs and
suggestion in further novel therapeutic options. Stem Cells 2017;35:2060-2070.
PMID- 28514508
TI - Methadone for neuropathic pain in adults.
AB - BACKGROUND: This review replaces an earlier review, "Methadone for chronic non
cancer pain in adults". This review serves to update the original and includes
only studies of neuropathic pain. Methadone belongs to a class of analgesics
known as opioids, that are considered the cornerstone of therapy for moderate-to
severe postsurgical pain and pain due to life-threatening illnesses; however,
their use in neuropathic pain is controversial. Methadone has many
characteristics that differentiate it from other opioids, which suggests that it
may have a different efficacy and safety profile. OBJECTIVES: To assess the
analgesic efficacy and adverse events of methadone for chronic neuropathic pain
in adults. SEARCH METHODS: We searched the following databases: CENTRAL (CRSO),
MEDLINE (Ovid), and Embase (Ovid), and two clinical trial registries. We also
searched the reference lists of retrieved articles. The date of the most recent
search was 30 November 2016. SELECTION CRITERIA: We included randomised, double
blind studies of two weeks' duration or longer, comparing methadone (in any dose,
administered by any route, and in any formulation) with placebo or another active
treatment in chronic neuropathic pain. DATA COLLECTION AND ANALYSIS: We used
standard methodological procedures expected by Cochrane. Two review authors
independently considered trials for inclusion in the review, assessed risk of
bias, and extracted data. There were insufficient data to perform pooled
analyses. We assessed the overall quality of the evidence for each outcome using
GRADE and created a 'Summary of findings' table. MAIN RESULTS: We included three
studies, involving 105 participants. All were cross-over studies, one involving
19 participants with diverse neuropathic pain syndromes, the other two involving
86 participants with postherpetic neuralgia. Study phases ranged from 20 days to
approximately eight weeks. All administered methadone orally, in doses ranging
from 10 mg to 80 mg daily. Comparators were primarily placebo, but one study also
included morphine and tricyclic antidepressants.The included studies had several
limitations related to risk of bias, particularly incomplete reporting, selective
outcome reporting, and small sample sizes.There were very limited data for our
primary outcomes of participants with at least 30% or at least 50% pain relief.
Two studies reported that 11/29 participants receiving methadone achieved 30%
pain relief versus 7/29 participants receiving placebo. Only one study presented
data in a manner that allowed us to calculate the number of participants with at
least 50% pain relief. None of the 19 participants achieved a 50% reduction in
pain intensity, either when receiving methadone or when receiving placebo. No
study provided data for our other primary outcomes of Patient Global Impression
of Change scale (PGIC) much or very much improved (equivalent to at least 30%
pain relief) and PGIC very much improved (equivalent to at least 50% pain
relief).For secondary efficacy outcomes, one study reported maximum and mean pain
intensity and pain relief, and reported statistically significant improvements
versus placebo for all outcomes with 20 mg daily doses of methadone, but not with
10 mg daily doses. The second study reported differences in pain reduction
between methadone (n = 26) and morphine (n = 38) and found morphine to be
statistically superior. The third study reported the number of responders
(variously defined) for several pain and functional outcomes and found methadone
to be statistically superior to placebo for the outcomes of categorical pain
intensity and evoked pain. In the two studies that reported data, 0/29
participants withdrew due to lack of efficacy, whereas 4/29 participants withdrew
due to adverse events while taking methadone versus 3/29 while taking placebo.One
study reported incidences for several individual adverse events, but found a
statistically significant increased incidence for methadone over placebo for only
one event, dizziness. The other studies did not report data in a manner that
enabled us to analyze adverse events. There were no serious adverse events or
deaths reported.We assessed the quality of the evidence as very low for all
efficacy and safety outcomes using GRADE, primarily because of the heterogeneity
of study designs and populations, short durations, cross-over methodology, and
few participants and events. AUTHORS' CONCLUSIONS: The three studies provide very
limited, very low quality evidence of the efficacy and safety of methadone for
chronic neuropathic pain, and there were too few data for pooled analysis of
efficacy or harm, or to have confidence in the results of the individual studies.
No conclusions can be made regarding differences in efficacy or safety between
methadone and placebo, other opioids, or other treatments.
PMID- 28514510
TI - Injury to the infrapatellar branch of the saphenous nerve during tendon graft
harvesting for knee ligament reconstruction: An ultrasound simulation study.
AB - The clinical anatomy of the infrapatellar branch of the saphenous nerve (IPBSN)
is of particular importance during operations in the area of the knee, especially
when material for anterior cruciate ligament reconstruction is harvested. The
nerve can easily be injured during the harvesting procedure, leading to
postoperative complications that reduce quality of life. Three different skin
incisions are commonly used during hamstring tendon harvesting: horizontal,
vertical, and oblique. The aim of this ultrasound simulation study was to assess
the risk of IPBSN injury associated with the type of skin incision and the point
of-emergence of the IPBSN relative to the sartorius muscle. Thirty healthy
volunteers (60 lower limbs) were recruited for identification of the IPBSN. When
it was found, using a high-frequency ultrasound probe, three different 3 cm skin
incisions over the pes anserinus were simulated. Vertical, horizontal, or oblique
lines simulating incisions were marked over the pes anserinus and ultrasound was
used to visualize the structures that could be injured during the marked
incisions. The IPBSN was visualized in 58 lower limbs (96.7%). The results of the
simulation study indicated that the vertical incision should be avoided during
hamstring tendon harvesting, as it is associated with a significantly higher risk
of injury (25.9%) to the IPBSN than the horizontal (3.5%) or oblique (8.6%)
incisions. We recommend that a preoperative ultrasound assessment of IPBSN
anatomy be performed to minimize the risk of iatrogenic injury to the nerve and
associated complications. Clin. Anat. 30:868-872, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28514509
TI - The dimensions of the tarsal sinus and canal in different foot positions and its
clinical implications.
AB - This study presents a reference for the dimensions of the tarsal sinus and canal
in healthy adults in different foot positions to facilitate understanding of the
kinematics of the subtalar joint, the effect of an implant, and other clinical
issues. In a 3D CT stress test on 20 subjects, the right foot was forced into a
neutral and eight different extreme foot positions while CT scans were obtained.
The bones were segmented in the neutral foot position. The kinematics of the
bones in the extreme positions were determined relative to the neutral position.
The dimensions of the tarsal sinus and canal were calculated by determining the
radii of the maximal inscribed spheres at 20 equidistant locations along an axis
in 3D surface models of the tali and calcanei in each foot position. The radii
were small on the medial side and increased laterally. Medial from the middle,
the radii were small and not significantly different among the various foot
positions. At the lateral side, the dimensions were affected mainly by eversion
or inversion and less by dorsiflexion or plantarflexion. The pattern was
reproducible among subjects, but there were between-subject differences. The
dimensions are mostly determined by rotation in the frontal plane. A pivot point
was found medial from the middle. These data serve as a reference and model for
predicting the effect of sinus implants and understanding such clinical problems
as sinus tarsi syndrome. Between-subjects differences have to be taken into
account. Clin. Anat. 30:1049-1057, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28514511
TI - Experiences of xerostomia after radiotherapy in patients with head and neck
cancer: A qualitative study.
AB - AIMS AND OBJECTIVES: To describe the experiences of radiation-induced xerostomia
in patients with head and neck cancer. BACKGROUND: Xerostomia is the most
commonly occurring complication during and following radiotherapy. It can persist
for several months or years and can have a significant impact on patients'
quality of life. DESIGN: This was a qualitative descriptive study. METHODS: Semi
structured interviews were conducted with a sample of 20 participants. Inductive
content analysis was used to analyse the qualitative data. RESULTS: Analysis of
the manifest content identified five categories: communication problems, physical
problems, psychosocial problems, treatment problems and relief strategies. The
latent content was formulated into a theme: due to lack of information from
professionals, the patients had to find their own solutions for their problems.
CONCLUSIONS: Xerostomia is not only a biophysical symptom but also has a profound
effect on the emotional, intellectual and sociocultural dimensions of life. The
majority of patients continued to suffer from xerostomia and its associated
symptoms after radiotherapy, in part, because of a lack of professional support,
including the inability of nurses to provide oral health care. RELEVANCE TO
CLINICAL PRACTICE: Nurses need to be knowledgeable about the effects of
radiotherapy on oral mucosa and about appropriate interventions. The healthcare
system requires a symptom management platform for radiation-induced
complications, to help patients, their families and healthcare professionals
obtain information about self-care, treatments and relief strategies.
PMID- 28514512
TI - Prevalence of the aberrant right subclavian artery reported in a published
systematic review of cadaveric studies: The impact of an outlier.
AB - The aberrant or anomalous right subclavian artery (ARSA), which arises directly
from the aortic arch and crosses to the right side usually behind the esophagus,
is a rare but clinically important anatomical variant. A published systematic
review (SR) of 15 cadaveric studies on ARSA reported that prevalence ranged from
0.2% to 13.3% of the general population; the total unweighted prevalence of ARSA
was 325 cases in 13,208 bodies or 2.46%. The present review, however, found that
the 13.3% figure was for 133 cases from a larger case series without a
denominator. Three other studies either had an imprecise denominator or were
limited to congenital conditions associated with ARSA. After exclusions and
modifications, ARSA prevalence for the remaining 11 studies in the SR ranged from
0.19%, with a 95% confidence interval (CI) of 0.00-1.08%, to 2.52% (CI= 0.69
6.32%). The unweighted prevalence for all 11 studies combined was 1.23%, and the
pooled prevalence estimate from a meta-analysis was 1.30% (CI = 0.86-1.82%). In
conclusion, overall findings from SRs on the prevalence of rare anatomical
variants such as ARSA may be affected by outliers. Clin. Anat. 30:1024-1028,
2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28514513
TI - Comprehensive database of Manufactured Gas Plant tars. Part C. Heterocyclic and
hydroxylated polycyclic aromatic hydrocarbons.
AB - RATIONALE: Coal tars are a mixture of organic and inorganic compounds that were
by-products from the manufactured gas and coke making industries. The tar
compositions varied depending on many factors such as the temperature of
production and the type of retort used. For this reason a comprehensive database
of the compounds found in different tar types is of value to understand both how
their compositions differ and what potential chemical hazards are present. This
study focuses on the heterocyclic and hydroxylated compounds present in a
database produced from 16 different tars from five different production
processes. METHODS: Samples of coal tar were extracted using accelerated solvent
extraction (ASE) and derivatized post-extraction using N,O
bis(trimethylsilyl)trifluoroacetamide (BSTFA) with 1% trimethylchlorosilane
(TMCS). The derivatized samples were analysed using two-dimensional gas
chromatography combined with time-of-flight mass spectrometry (GCxGC/TOFMS).
RESULTS: A total of 865 heterocyclic compounds and 359 hydroxylated polycyclic
aromatic hydrocarbons (PAHs) were detected in 16 tar samples produced by five
different processes. The contents of both heterocyclic and hydroxylated PAHs
varied greatly with the production process used, with the heterocyclic compounds
giving information about the feedstock used. Of the 359 hydroxylated PAHs
detected the majority would not have been be detected without the use of
derivatization. CONCLUSIONS: Coal tars produced using different production
processes and feedstocks yielded tars with significantly different heterocyclic
and hydroxylated contents. The concentrations of the individual heterocyclic
compounds varied greatly even within the different production processes and
provided information about the feedstock used to produce the tars. The
hydroxylated PAH content of the samples provided important analytical information
that would otherwise not have been obtained without the use of derivatization and
GCxGC/TOFMS.
PMID- 28514514
TI - Alternation between short- and long photoperiod reveals hypothalamic gene
regulation linked to seasonal body weight changes in Djungarian hamsters
(Phodopus sungorus).
AB - Djungarian hamsters are able to reduce their body weight by more than 30% in
anticipation of the winter season. This particular adaptation to extreme
environmental conditions is primarily driven by a natural reduction in day length
and conserved under laboratory conditions. We used this animal model to
investigate hypothalamic gene expression linked to body weight regulation behind
this physiological phenomenon. After an initial collective short photoperiod (SP)
adaptation for 14 weeks from a preceding long photoperiod (LP), hamsters were re
exposed to LP for either 6 or 14 weeks, followed by a second re-exposure to SP
for 8 weeks. Our data showed that re-exposure to LP led to an increase in body
weight. In the hypothalamus Dio2, Vimentin, Crbp1 and Grp50 expression increased,
whereas expression of Dio3, Mct8 and Srif decreased. The changes in body weight
and gene expression were reversible in most hamsters after a further re-exposure
to SP following 6 or 14 weeks in LP. Interestingly, after 14 weeks in LP, body
weight loss was pronounced in six hamsters re-exposed to SP, but five hamsters
did not respond. In nonresponding hamsters, a different gene expression pattern
was manifested, with the exception of Dio2, which was reduced not only in SP re
exposed hamsters, but also in hamsters maintained in LP. Taken together, these
data suggest that body weight regulation appears to be tightly linked to a co
ordinated regulation of several genes in the hypothalamus, including those
involved in thyroid hormone metabolism.
PMID- 28514515
TI - Detailed anatomy of the abducens nerve in the lateral rectus muscle.
AB - The aims of this study were to elucidate the detailed anatomy of the abducens
nerve in the lateral rectus muscle (LRM) and the intramuscular innervation
pattern using Sihler staining. In this cohort study, 32 eyes of 16 cadavers were
assessed. Dissection was performed from the LRM origin to its insertion. The
following distances were measured: from LRM insertion to the bifurcation point of
the abducens nerve, from LRM insertion to the entry site of the superior branch
or inferior branch, from the upper border of the LRM to the entry site of the
superior branch, from the lower border of LRM to the entry site of inferior
branch, and the widths of the main trunk and superior and inferior branches. The
single trunk of the abducens nerve divided into two branches 37 mm from insertion
of the LRM, and 22 of 32 (68.8%) orbits showed only two superior and inferior
branches with no subdivision. The superior branch entered the LRM more anteriorly
(P = 0.037) and the superior branch was thinner than the inferior branch (P =
0.040). The most distally located intramuscular nerve ending was observed at 52.9
+/- 3.5% of the length of each muscle. Non-overlap between the superior and
inferior intramuscular arborization of the nerve was detected in 27 of 32 cases
(84.4%). Five cases (15.6%) showed definite overlap of the superior and inferior
zones. This study revealed the detailed anatomy of the abducens nerve in the LRM
and provides helpful information to understand abducens nerve palsy. Clin. Anat.
30:873-877, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28514516
TI - Which factors most influence referral for restorative dental treatment under
sedation and general anaesthesia in children with complex disabilities: caries
severity, child functioning, or dental service organisation?
AB - BACKGROUND: The UN Convention on the Rights of the Child gives all children right
to the highest standard of services for treatment and rehabilitation. For
children with disabilities, sedation and general anaesthesia (GA) are often
indicated for dental treatment; however, accessibility to this varies. The
International Classification of Functioning, Disability and Health - Child and
Youth version (ICF-CY) enables a biopsychosocial description of children
undergoing dental treatment. AIM: To investigate conscious sedation and GA in
children with complex disabilities and manifest caries and analyse how caries,
child functioning, and dental service organisation relate to dental GA (DGA),
comparing Argentina, France, and Sweden using the ICF-CY. DESIGN: Quantitative,
cross-sectional; data collected through structured interviews, observation, and
dental records. RESULTS: Sedation and DGA were common. Children with limitations
in interpersonal interactions and relationships were more likely to have had DGA
(OR: 5.3, P = 0.015). Level of caries experience was strongly correlated with
experience of DGA. There were significant differences between countries regarding
caries prevalence, sedation, DGA, and functional and environmental factors.
CONCLUSIONS: Although caries experience and child functioning are important,
dental health service organisation had the most impact on the incidence of DGA,
and for the use of conscious sedation, for children with complex disabilities.
PMID- 28514517
TI - Early childhood caries and psychological perceptions on child's oral health
increase the feeling of guilt in parents: an epidemiological survey.
AB - AIM: To assess whether parents feel guilty for their children's oral problems,
associating this feeling with socio-economic, demographic, and psychological
factors. DESIGN: We included 1313 parent-and-child pairs in this study. The
children were 2-4 years old. Parents answered questionnaires on socio-economic
and demographic data, and on psychological variables. Sixteen trained dentists
(kappa > 0.8) examined the children for oral hygiene (the presence and absence of
plaque), early childhood caries (ECC; no caries, low and high severity),
malocclusion (the presence and absence), and traumatic dental injuries (TDI; the
presence and absence). We analysed the data with a hierarchical regression.
RESULTS: Twenty-four percentage of parents reported feeling guilty for the oral
problems in their children; 26.3% of the children presented with caries, 39.8%
malocclusion, 22.9% TDI. Of the parents who felt guilty, 54% thought that their
children had problems in their teeth, and most of them (82%) thought that the
problem could have been avoided. The feeling of guilt in parents was
significantly associated with ECC and the psychological variables: the thought
that the child had problems in his/her teeth and the thought that the problem
could have been avoided. CONCLUSION: Parents feel more guilty with increased
caries severity in their children, and the likelihood of feeling guilty increases
when parents believe that their child has an oral problem or that this problem
could have been avoided.
PMID- 28514518
TI - A Retrosynthesis Approach for Biocatalysis in Organic Synthesis.
AB - For the planning of an organic synthesis route, the disconnection approach guided
by retrosynthetic analysis of possible intermediates and the chemical reactions
involved, back to ready available starting materials, is well established. In
contrast, such concepts just get developed for biocatalytic routes. In this
Review we highlight functional group interconversions catalyzed by enzymes. The
article is organized rather by chemical bonds formed-exemplified for C-N, C-O-
and C-C-bonds-and not by enzyme classes, covering a broad range of reactions to
incorporate the desired functionality in the target molecule. Furthermore, the
successful use of biocatalysts, also in combination with chemical steps, is
exemplified for the synthesis of various drugs and advanced pharmaceutical
intermediates such as Crispine A, Sitagliptin and Atorvastatin. This Review also
provides some basic guidelines to choose the most appropriate enzyme for a
targeted reaction keeping in mind aspects like commercial availability, cofactor
requirement, solvent tolerance, use of isolated enzymes or whole cell recombinant
microorganisms aiming to assist organic chemists in the use of enzymes for
synthetic applications.
PMID- 28514520
TI - Patient involvement in research - participants or collaborators?
PMID- 28514519
TI - Patient involvement vs. patient participation in qualitative research in the
development of PROMs.
PMID- 28514521
TI - Combining frozen-density embedding with the conductor-like screening model using
Lagrangian techniques for response properties.
AB - We present the explicit derivation of an approach to the multiscale description
of molecules in complex environments that combines frozen-density embedding (FDE)
with continuum solvation models, in particular the conductor-like screening model
(COSMO). FDE provides an explicit atomistic description of molecule-environment
interactions at reduced computational cost, while the outer continuum layer
accounts for the effect of long-range isotropic electrostatic interactions. Our
treatment is based on a variational Lagrangian framework, enabling rigorous
derivations of ground- and excited-state response properties. As an example of
the flexibility of the theoretical framework, we derive and discuss FDE + COSMO
analytical molecular gradients for excited states within the Tamm-Dancoff
approximation (TDA) and for ground states within second-order Moller-Plesset
perturbation theory (MP2) and a second-order approximate coupled cluster with
singles and doubles (CC2). It is shown how this method can be used to describe
vertical electronic excitation (VEE) energies and Stokes shifts for uracil in
water and carbostyril in dimethyl sulfoxide (DMSO), respectively. In addition,
VEEs for some simplified protein models are computed, illustrating the
performance of this method when applied to larger systems. The interaction terms
between the FDE subsystem densities and the continuum can influence excitation
energies up to 0.3 eV and, thus, cannot be neglected for general applications. We
find that the net influence of the continuum in presence of the first FDE shell
on the excitation energy amounts to about 0.05 eV for the cases investigated. The
present work is an important step toward rigorously derived ab initio multilayer
and multiscale modeling approaches. (c) 2017 Wiley Periodicals, Inc.
PMID- 28514522
TI - Use of Reversible Contraceptive Methods Among U.S. Women with Physical or Sensory
Disabilities.
AB - CONTEXT: Women with disabilities experience a higher rate of adverse pregnancy
outcomes than women without disabilities. Preventing or delaying pregnancy when
that is the best choice for a woman is a critical strategy to reducing pregnancy
related disparities, yet little is known about current contraceptive use among
women with disabilities. METHODS: A cohort of 545 reproductive-age women with
physical disabilities (i.e., difficulty walking, climbing, dressing or bathing)
or sensory disabilities (i.e., difficulty with vision or hearing) was identified
from among participants in the 2011-2013 National Survey of Family Growth. Those
at risk for unplanned pregnancy were categorized by whether they were using
highly effective reversible contraceptive methods (IUD, implant), moderately
effective ones (pill, patch, ring, injectable), less effective ones (condoms,
withdrawal, spermicides, diaphragm, natural family planning) or no method.
Multinomial regression was conducted to examine the association between
disability and type of contraceptive used. RESULTS: Some 39% of women with
disabilities were at risk of unplanned pregnancy, and 27% of those at risk were
not using contraceptives. The presence of disability was associated with
decreased odds of using highly effective methods or moderately effective methods,
rather than less effective ones (odds ratio, 0.6 for each), but had no
association with using no method. CONCLUSION: There is a significant need to
reduce contraceptive disparities related to physical or sensory disabilities.
Future research should explore the extent to which contraceptive use differs by
type and severity of disability, as well as identify contextual factors that
contribute to any identified differences.
PMID- 28514523
TI - The views of older people and health professionals about dignity in acute
hospital care.
AB - AIMS AND OBJECTIVES: To report the findings from interviews conducted as part of
a wider study on interventions to support dignified care in older people in acute
hospital care. The data in this study present the interview data. BACKGROUND:
Dignity is a complex concept. Despite a plethora of recommendations on how to
achieve dignified care, it remains unclear how to attain this in practice and
what the priorities of patients and staff are in relation to dignity. DESIGN: A
purposive sample of older patients and staff took part in semi-structured
interviews and gave their insight on the meaning of dignity and examples of what
sustains and breaches a patient's dignity in acute hospital care. METHOD:
Thirteen patients and 38 healthcare professionals in a single metropolitan
hospital in the UK interviewed. Interviews were transcribed verbatim and
underwent a thematic analysis. RESULTS: The meaning of dignity was broadly agreed
on by patients and staff. Three broad themes were identified: the meaning of
dignity, staffing level and its impact on dignity, and organisational culture and
dignity. Registered staff of all healthcare discipline and student nurses report
very little training on dignity or care of the older person. CONCLUSION: There
remain inconsistencies in the application of dignified care. Staff behaviour, a
lack of training and the organisational processes continue to result in breaches
to dignity of older people. Clinical nurses have a major role in ensuring
dignified care for older people in hospital. RELEVANCE TO CLINICAL PRACTICE:
There needs to be systematic dignity-related training with regular refreshers.
This education coupled with measures to change the cultural attitudes in an
organisation towards older peoples' care should result in long-term improvements
in the level of dignified care. Hospital managers have an important role in
changing system to ensure that staff deliver the levels of care they aspire to.
PMID- 28514524
TI - Transition from hospital to home: Parents' perception of their preparation and
readiness for discharge with their preterm infant.
AB - AIMS AND OBJECTIVES: To explore the experiences of parents with babies born
between 28-32 weeks' gestation during transition through the neonatal intensive
care unit and discharge to home. BACKGROUND: Following birth of a preterm baby,
parents undergo a momentous journey through the neonatal intensive care unit
prior to their arrival home. The complexity of the journey varies on the degree
of prematurity and problems faced by each baby. The neonatal intensive care unit
environment has many stressors and facilitating education to assist parents to
feel ready for discharge can be challenging for all health professionals. DESIGN:
Qualitative descriptive design. METHODS: The project included two phases, pre-
and postdischarge, to capture the experiences of 20 couples (40 parents), whilst
their baby was a neonatal intensive care unit inpatient and then after discharge.
Face-to-face interviews, an online survey and telephone interviews were employed
to gather parent's experiences. Constant comparative analysis was used to
identify commonalities between experiences. Recruitment and data collection
occurred from October 2014-February 2015. RESULTS/FINDINGS: Overlapping themes
from both phases revealed three overarching concepts: effective parent staff
communication; feeling informed and involved; and being prepared to go home.
CONCLUSION: Our findings can be used to develop strategies to improve the
neonatal intensive care unit stay and discharge experience for parents. Proposed
strategies would be to improve information transfer, promote parental contact
with the multidisciplinary team, encourage input from fathers to identify their
needs and facilitate parental involvement according to individual needs within
families. RELEVANCE TO CLINICAL PRACTICE: Providing information to parents during
their time in hospital, in a consistent and timely manner is an essential
component of their preparation when transitioning to home.
PMID- 28514525
TI - Responsiveness of the Arabic version of the ECOHIS to dental rehabilitation under
general anaesthesia.
AB - BACKGROUND: The Arabic version of the Early Childhood Oral Health Impact Scale (A
ECOHIS) has been validated, but its ability to detect change was not tested. AIM:
To evaluate the responsiveness of the A-ECOHIS to dental rehabilitation under
general anaesthesia (DRGA). DESIGN: A consecutive sample of 131 parents of
children aged 6 years or younger, scheduled for DRGA were recruited from three
public hospitals. The parents completed the A-ECOHIS before and 4 weeks following
DRGA. The responsiveness of the A-ECOHIS was assessed by evaluating changes in
scores before and after DRGA, and by measuring the change in scores in relation
to the global question. RESULTS: The A-ECOHIS scores were higher among parents
who reported poor oral health on the global question than those reporting better
oral health (P = 0.001). There was a significant reduction in the scores at
follow-up (P < 0.001). The effect size was 1.5 for the total scale, and 1.3 and
1.6 for the child and family impacts, respectively. After DRGA, the child and
family impact section scores decreased by 78.6% and 77.9%, respectively. The
majority of parents reported improvement in children's overall oral health
related quality of life post-operatively (94%). CONCLUSION: The A-ECOHIS was
responsive to DRGA.
PMID- 28514526
TI - Direct medial approach in surgical fixation of fractures in the posterior aspect
of the medial malleolus.
AB - Fractures in the posterior aspect of the medial malleolus form an important
subset of ankle fractures and the indications for fixation include involvement of
> 25% of the articular surface or an articular step off by > 2 mm. Several
approaches have been described but there has been no recent study on the direct
medial approach. Five fresh frozen cadaveric ankles were dissected using the
direct medial approach. A longitudinal incision of 10 cm was centered directly
over the medial malleolus and deepened straight down to the bone. The periosteum
was identified over the distal tibia and careful subperiosteal dissection yielded
access to the posterior aspect of the medial malleolus. We investigated the
relationship of the neurovascular bundle to the incision by measuring the
distance from the center of the medial malleolus to the closest aspect of the
bundle. The mean distance from the center of the medial malleolus to the
neurovascular bundle was only 2.64 cm (95% CI: 2.06 to 3.22 cm). We found that
the neurovascular bundle could be avoided if a periosteal sheath was developed
during the dissection and elevated off the posterior aspect of the medial
malleolus. The direct medial approach can be performed safely by creating a
periosteal sheath through subperiosteal dissection, and the distance of the
neurovascular bundle from the incision allows for a good margin of safety during
surgery. This approach can be extended proximally and distally and the medial
malleolus can be fixed concurrently. Clin. Anat. 31:605-607, 2018. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28514528
TI - Overcoming the Instability of Nanoparticle-Based Catalyst Films in Alkaline
Electrolyzers by using Self-Assembling and Self-Healing Films.
AB - Engineering stable electrodes using highly active catalyst nanopowders for
electrochemical water splitting remains a challenge. We report an innovative and
general approach for attaining highly stable catalyst films with self-healing
capability based on the in situ self-assembly of catalyst particles during
electrolysis. The catalyst particles are added to the electrolyte forming a
suspension that is pumped through the electrolyzer. Particles with negatively
charged surfaces stick onto the anode, while particles with positively charged
surfaces stick to the cathode. The self-assembled catalyst films have self
healing properties as long as sufficient catalyst particles are present in the
electrolyte. The proof-of-concept was demonstrated in a non-zero gap alkaline
electrolyzer using NiFe-LDH and Nix B catalyst nanopowders for anode and cathode,
respectively. Steady cell voltages were maintained for at least three weeks
during continuous electrolysis at 50-100 mA cm-2 .
PMID- 28514529
TI - The effect of repeated freeze-thaw cycles on human muscle tissue visualized by
postmortem computed tomography (PMCT).
AB - The aim of this study was to determine whether effects of repetitive freeze-thaw
cycles, with various thawing temperatures, on human muscle tissue can be
quantified using postmortem computed tomography (PMCT) technology. An additional
objective was to determine the preferred thawing temperature for muscle tissue in
this study. Human cadaver upper extremities were divided into two different
thawing temperature groups and underwent a series of four freeze-thaw cycles in
total. Axial CT scans were performed after each cycle. CT attenuation (in
Hounsfield units, HU) was measured in four muscles of the upper extremities. HU
values changed significantly with the introduction of each subsequent freeze-thaw
cycle. Moreover, the changes in HU values were different for each thawing group.
There was a significant increase of HU values in both groups between t0 and t1 .
Unfrozen tissue showed large variation of HU values in all samples. It was
possible to distinguish between samples thawed at different thawing temperatures
based on their respective HU values. It is advisable to keep the number of freeze
thaw cycles to just one, if the human cadaveric tissue is to be used for
educational purposes. The preferred thawing temperature in this study is 2
degrees C. Clin. Anat. 30:799-804, 2017. (c) 2017Wiley Periodicals, Inc.
PMID- 28514527
TI - Efficacy and Safety of Injectable Robenacoxib for the Treatment of Pain
Associated With Soft Tissue Surgery in Dogs.
AB - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are used routinely to
control pain and inflammation after surgery in dogs. Robenacoxib is a
cyclooxygenase-2 selective NSAID. HYPOTHESIS/OBJECTIVE: Assess the clinical
efficacy and safety of an injectable formulation of robenacoxib in dogs
undergoing surgery. ANIMALS: Three hundred and seventeen client-owned dogs (N =
159 robenacoxib or N = 158 placebo). METHODS: In this prospective, multicenter,
randomized, masked, placebo-controlled, parallel-group study, dogs received a SC
injection of either robenacoxib, at a target dose of 2.0 mg/kg, or placebo once
prior to surgery and for 2 additional days postoperatively. Pain assessments were
performed using the short form of the Glasgow Composite Measure Pain Scale (CMPS
SF). The primary efficacy variable was treatment success/failure, with failure
defined as the need for rescue therapy to control pain or withdrawal of the dog
from the study due to an adverse event. RESULTS: Significantly (P = .006) more
dogs administered robenacoxib were considered treatment successes (108 of 151,
73.7%) compared to dogs given placebo (85 of 152, 58.1%). Total pain scores (P <
.01), pain at the surgery sites (response to touch, P < .01), and
posture/activity (P < .05) were significantly improved at 3, 5, and 8 hours
postextubation in dogs receiving robenacoxib versus placebo. CONCLUSIONS AND
CLINICAL IMPORTANCE: Robenacoxib administered by SC injection prior to surgery
and for 2 additional days postoperatively was effective and well tolerated in the
control of postoperative pain and inflammation associated with soft tissue
surgery in dogs.
PMID- 28514530
TI - Curious, thoughtful and affirmative-Young children's meanings of participation in
healthcare situations when using an interactive communication tool.
AB - AIMS AND OBJECTIVES: To describe young children's demonstrated participation in
healthcare situations while using an interactive communication tool. BACKGROUND:
Participation is a multidimensional concept influenced by situational and
contextual issues. In child participation, verbal and nonverbal communicative
expressions are of interest, as both demonstrate the child's perspective.
Children have a right to participate in all situations that matter to them, for
instance healthcare situations. Children, understood as social actors, express a
wish and a need to participate in these situations to get information and to
enable preparation. DESIGN/METHOD: In a pilot study, video observations were used
to capture the children's use of the interactive communication tool in healthcare
situations. A hermeneutic analysis was conducted to achieve a deeper
understanding of the children's demonstrated cues of participation. RESULTS: The
expressed cues of participation were understood as having either a curious,
thoughtful or affirmative meaning of participation and there was a continuous
movement between them. Curious cues were expressed when introducing or
reintroducing the tool in the situation and demonstrated a wish to get knowledge
of the things shown on the screen or to perform the virtual tasks. Thoughtful
cues slowed down the progression of the situation when the children needed time
to think or adapt to the virtual procedures. Affirmative cues were self-rewarding
and demonstrated at successful task performance. CONCLUSION: An interactive
communication tool used in healthcare situations can promote young children's
understanding and facilitate their situated participation, which potentially
reduces feelings of distress or anxiety. This innovative use of interactive
technology within paediatric health care provides new ways of revealing the
child's perspective in the situation. RELEVANCE TO CLINICAL PRACTICE: Interactive
technology improves understanding and participation of children in healthcare
situations, which impact them positively, both in the present and for the future.
A communication tool enhances professionals' opportunities to adopt a child
centred approach by responding sensitively to the children's expressions.
PMID- 28514531
TI - Safety and service: Reframing the purpose of nursing to decision-makers.
PMID- 28514533
TI - Antecedents and consequences of workplace violence against nurses: A qualitative
study.
AB - AIMS AND OBJECTIVES: To explore Iranian nurses' perceptions of and experiences
with the antecedents and consequences of workplace violence perpetrated by
patients, patients' relatives, colleagues and superiors. BACKGROUND: Workplace
violence against nurses is a common problem worldwide, including in Iran.
Although many studies have reviewed the antecedents and consequences of workplace
violence, limited information is available on this topic. An understanding of the
predisposing factors for violence and the consequences of violence is essential
to developing programs to prevent and manage workplace violence. DESIGN:
Qualitative descriptive design. METHODS: In this qualitative study, 22
unstructured, in-depth interviews were conducted with registered nurses who had
experienced workplace violence and who were selecting using purposive sampling in
nine hospitals. Inductive content analysis was used to analyse the data. RESULTS:
Five categories emerged as predisposing factors: unmet expectations of
patients/relatives, inefficient organisational management, inappropriate
professional communication, factors related to nurses and factors related to
patients, patients' relatives and colleagues. Individual, familial and
professional consequences were identified as outcomes of workplace violence
against nurses. CONCLUSIONS: Workplace violence by patients/their relatives and
colleagues/superiors is affected by various complicated factors at the individual
and organisational levels. In addition to negatively affecting nurses' individual
and family lives, workplace violence may lead to a lower quality of patient care
and negative attitudes towards the nursing profession. RELEVANCE TO CLINICAL
PRACTICE: Identifying factors, which lead to workplace violence, could help
facilitate documenting and reporting such incidents as well as developing the
necessary interventions to reduce them. Furthermore, native instruments must be
developed to predict and monitor violence.
PMID- 28514534
TI - Anticipatory vigilance: A grounded theory study of minimising risk within the
perioperative setting.
AB - AIMS AND OBJECTIVES: To explore and explain how nurses minimise risk in the
perioperative setting. BACKGROUND: Perioperative nurses care for patients who are
having surgery or other invasive explorative procedures. Perioperative care is
increasingly focused on how to improve patient safety. Safety and risk management
is a global priority for health services in reducing risk. Many studies have
explored safety within the healthcare settings. However, little is known about
how nurses minimise risk in the perioperative setting. DESIGN: Classic grounded
theory. METHODS: Ethical approval was granted for all aspects of the study.
Thirty-seven nurses working in 11 different perioperative settings in Ireland
were interviewed and 33 hr of nonparticipant observation was undertaken.
Concurrent data collection and analysis was undertaken using theoretical
sampling. Constant comparative method, coding and memoing and were used to
analyse the data. RESULTS: Participants' main concern was how to minimise risk.
Participants resolved this through engaging in anticipatory vigilance (core
category). This strategy consisted of orchestrating, routinising and momentary
adapting. CONCLUSION: Understanding the strategies of anticipatory vigilance
extends and provides an in-depth explanation of how nurses' behaviour ensures
that risk is minimised in a complex high-risk perioperative setting. This is the
first theory situated in the perioperative area for nurses. RELEVANCE TO CLINICAL
PRACTICE: This theory provides a guide and understanding for nurses working in
the perioperative setting on how to minimise risk. It makes perioperative nursing
visible enabling positive patient outcomes. This research suggests the need for
training and education in maintaining safety and minimising risk in the
perioperative setting.
PMID- 28514535
TI - Analysis of mortality in individuals over 60 years of age in inner Mongolia
between 2008 and 2012.
AB - Our study was designed to determine the cause of death in people over 60 years of
age in Inner Mongolia. We performed quantitative analysis of mortality rate, with
a special focus on the population characteristics in the Inner Mongolia region of
China to provide a reference for future studies. Data were obtained from the
Centers for Disease Control from six monitoring points of Death Registry System
(DRS) in Inner Mongolia, covering the period 2008-2012 years. We calculated the
crude mortality rate over five years, as well as the causes of death and
potential-years of life lost (PYLL) by gender over the same time period. We also
calculated the crude mortality across different age-specific groups, and analyzed
cause of death across these groups. Between 2008 and 2012, the crude mortality
rate of individuals in Inner Mongolia aged 60 years or older was 3366,73 /100
000. The crude mortality rate was higher among males (4158,68/100 000) than among
females (2633,22/100 000), resulting in a male-female mortality ratio of 1,58 and
a total PYLL of 48 968 person-years for males and females combined. Diseases of
the circulatory system were the greatest contributor to mortality (1978,50/100
000) and PYLL (25 700 person-years).The frequency of deaths due to diseases of
the circulatory and respiratory systems increased with age, while the proportion
of neoplasms declined with age. The mortality of individuals in Inner Mongolia
over 60 years of age is moderate compared with studies of other Chinese
populations. Diseases of the circulatory system, neoplasms, and diseases of the
respiratory system were the leading causes of death. We therefore recommend that
healthy lifestyle choices be advocated among the elderly to reduce the incidence
of chronic, non-communicable diseases.
PMID- 28514532
TI - The Dickkopf1-cytoskeleton-associated protein 4 axis creates a novel signalling
pathway and may represent a molecular target for cancer therapy.
AB - : Dickkopf 1 (DKK1) is a secreted protein and antagonizes oncogenic Wnt
signalling by binding to the Wnt co-receptor, low-density lipoprotein receptor
related protein 6. DKK1 has also been suggested to regulate its own signalling,
associated with tumour aggressiveness. However, the underlying mechanism by which
DKK1 promotes cancer cell proliferation has remained to be clarified for a long
time. The cytoskeleton-associated protein 4 (CKAP4), originally identified as an
endoplasmic reticulum membrane protein, was recently found to act as a novel DKK1
receptor. DKK1 stimulates cancer cell proliferation when CKAP4 is expressed on
the cell surface membrane. Although there are no tyrosine residues in the
intracellular region of CKAP4, CKAP4 forms a complex with PI3K upon the binding
of DKK1, leading to the activation of Akt. Both DKK1 and CKAP4 are frequently
expressed in pancreatic and lung tumours, and their simultaneous expression is
negatively correlated with prognosis. Knockdown of CKAP4 in cancer cells and
treatment of mice with the anti-CKAP4 antibody inhibit Akt activity in cancer
cells and suppress xenograft tumour formation, suggesting that CKAP4 may
represent a therapeutic target for cancers expressing both DKK1 and CKAP4. This
review will provide details of the novel DKK1-CKAP4 signalling axis that promotes
cancer proliferation and discuss the possibility of targeting this pathway in
future cancer drug development. LINKED ARTICLES: This article is part of a themed
section on WNT Signalling: Mechanisms and Therapeutic Opportunities. To view the
other articles in this section visit
http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.24/issuetoc.
PMID- 28514536
TI - [Life span, longevity and incidence of violence death in writers and poets].
AB - The article provides information on the mean age of death (MAD) those
professionally involved in literary work (22 028 men and women 4 651) assigned to
one of three categories: novelists, poets and writers-poets. Women any of the
investigated categories authentically lived longer than men (p<0,02). Analysis of
dynamics of mean age of death (MAD), starting from the 15th century BC to the end
of the 20th century, showed that this ratio gradually increased but uneven among
fiction writers and novelists, poets of both sexes, however, remained unchanged
at poets and poetesses have declined. Among men the very old (90+ years) were
5,38 % and 3,01 % writers-poets, whereas among women - 12,35 and 8,96 %,
respectively. Centenarians have surpassed 1,62 % of women novelists and 0,61 %
poets, then among men - 0,31 % and 0,49 % of writers, novelists and poets,
respectively. The frequency of violent deaths (homicide, suicide, accidents) is
also varied and was highest among poets, novelists, poets have minimum-novelists
occupied an intermediate position for these indicators. Histogram of MAD had 2
peakes type, characteristic for heterogeneous populations, with a sample of
"writers" heterogeneity was weakly expressed, however in a sample of "poets" was
very noticeable. Suggests that MAD, longevity, as well as the frequency of
violent deaths are related to processes associated with creativity.
PMID- 28514537
TI - [Suppression of alternative telomere lengthening in cancer cells with reverse
transcriptase inhibitors].
AB - Telomerase is a ribonucleoprotein enzyme that elongates telomeres and therefore
maintains chromosomal stability in germline, and in the majority of cancer cells,
during cell doubling. However, up to 30 % of human tumors of different types do
not express telomerase, but instead use an alternative lengthening of telomeres
(ALT). Here authors show that human tumor-derived ALT cell lines express a LINE-1
(L1) retrotransposon, which suggests its participation in telomere maintenance,
possibly by a "slippage" mechanism of telomeric DNA synthesis. Moreover,
suppression of the L1 encoded reverse transcriptase activity using an antisense
strategy, or treatment of the ALT cells with the reverse transcriptase inhibitor
3'-azido-2',3'-dideoxythymidine (AZT), induces progressive telomere loss, arrest
in G2-phase of the cell cycle, and, eventually, in cancer cell death. This
finding suggests an exciting opportunity for the cure of up to 30 % of cancer
cases.
PMID- 28514538
TI - [Lamin B1 and lamin B2 in human skin in the process of aging].
AB - The aim of this work was to study B type lamins in human skin at different ages.
Lamins B1 and B2 were detected in sections of the skin by indirect
immunohistochemistry. There were 62,3 % of dermal fibroblasts with positive
staining for lamin B1 at the period from 20 to 40 weeks of gestation. From birth
to 40 years, 41-42 % of fibroblasts containing lamin B1 were found in the dermis.
In age interval from 41 to 85 years, 57-60 % of dermal fibroblasts had a positive
staining for lamin B1. The number of fibroblasts containing lamin B2 was
gradually decreased from 80,6 to 68,6 % from 20 weeks of gestation to 85 years
old. Expression of lamin B1 in the nuclei of fibroblasts was reduced from birth
to 40 years old. Content of lamin B2 in the nuclei of fibroblasts was almost
constant from 20 weeks of gestation to 85 years old. Number of fibroblasts in
dermis was diminished with age. The most significant decrease in the number of
fibroblasts was observed from 20 weeks of gestation to 20 years old. Results
allow to suggest the participation of lamin B1 in triggering age-dependent
decrease in the number of fibroblasts in the dermis in humans.
PMID- 28514539
TI - [The age changes of lymphoid organs structure: review of literature].
AB - Numerous and often contradictory research results specify that the mechanism of
increased susceptibility to diseases in old age has no satisfactory explanation
so far. Together with it in literature almost completely there are no comparative
data on features of surgery and injury influence on a structure and functions of
lymphoid organs at patients of different age groups. However, lymph nodes are a
marker of activity of inflammatory process in the region, on their changes it is
possible to estimate precisely productivity of different medical actions, to
predict development of many complications, and, thus, successfully to take
actions for their prophylaxis. All this is especially important and actual
because of constant increase in average age, in life expectancy of human
population and strengthening of surgical activity at patients of advanced and old
age.
PMID- 28514540
TI - [Age-related changes in biogenic amine content and oxidative stress profile in
the rat hypothalamus in hyperhomocysteinemia].
AB - The article presents a detailed analysis of correlations between the content of a
variety of biogenic amines in the hypothalamic structures responsible for the
luteinizing hormone releasing hormone synthesis and secretion (the medial
preoptic area and median eminence) and such independent factors as total L
homocysteine plasma level elevation induced by L-methionine loading and aging.
Both a nature and a pattern of changes in oxidative stress profile were
evaluated. It was shown that ageing, when compared to hyperhomocysteinemia, is a
determining factor influencing biogenic amine content in the studied hypothalamic
structures. Unlike antioxidant defense system profile, considerable changes in
macromolecule oxidative modification were not found, which evidences a balanced
activity of pro- and antioxidant systems in the hypothalamus.
PMID- 28514541
TI - [Age-related expression of calcium-binding proteins in autonomic ganglionic
neurons].
AB - Calbindin 28 kDa (CB), calretinin (CR) and parvalbumin (PB) are belonged to
calcium-binding proteins which are widely distributed in the nervous system and
selectively expressed in certain population of neurons. These proteins are
expressed not only in the central nervous system, but also in the autonomic
ganglia. CB and PB are found in the sympathetic ganglia of rodents, CB and CR are
found in metasympathetic intramural ganglia. Their functions are poor understood
but one can suggest their important role in regulation of the Ca2+ level in the
cell. Salcium-binding proteins are also play an important role in the development
of autonomic neurons. There is an increasing of the percentage of CB and CR in
the metasympathetic intramural ganglia of small intestine in the early postnatal
development, whereas in sympathetic ganglia the percentage of CB is decreased.
Possibly, the functional meaning of such changes can be explained by the role of
calcium currents in the development of neurons and the synaptic transmission.
PMID- 28514542
TI - [Neurohumoral changes in rats of different aged groups on the background of
injection of cryopreserved nucleated cells of cord blood].
AB - The application of the cryopreserved preparation of UCB NCs was accompanied by an
enhanced activity of all the neurohumoral regulation elements of heart rate,
although the absolute indices in 18- and 24-month-old animals did not reach
similar ones in younger age groups. Also we noted an increase of thyroid hormone
content in blood serum of aged rats, the level of which decreased with age. In
addition, there was shown that the introduction of UCB NCs during animal life
cycle (every 6 months) allowed keeping a functional state of the autonomic
nervous system at a "young" physiological level.
PMID- 28514543
TI - [The changes in hormonal status of the cardiovascular and the thyroid systems in
rats with 18-month type 2 diabetes mellitus].
AB - Among the most common complications of type 2 diabetes mellitus (DM2) are
disorders of the cardiovascular and the thyroid systems. The functions of these
systems may be weakened with increasing age. However, the mechanisms of these
disorders, including the role of alterations in the adenylyl cyclase signaling
system (ACSS), are not fully elucidated. Objective was to study thyroid status
and ACSS activity of the myocardium and the thyroid gland (TG) of rats with 8-
and 18-month DM2 (DM-8 and DM-18) as compared to control animals of the same age
(C-8 and C-18). In the myocardium of rats with DM2 an imbalance of beta
adrenergic regulation of ACSS was detected, and these disturbances were amplified
with increasing age. In the myocardium of rats of the C-18 group the disturbances
of ACSS hormonal regulation were also identified, but they were less pronounced.
In diabetic rats, the levels of free thyroxine and total triiodothyronine
decreased, the level of thyroid stimulating hormone (TSH) increased, and the
stimulatory effect of TSH on the ACSS in TG was attenuated, which indicates the
hypothyroid state in long-term DM2. In the C-18 group, these changes were absent.
Thus, in the myocardium and TG of rats with 18-month DM2 the hormonal regulation
of ACSS was violated, which may be one of the causes of cardiovascular pathology
and hypothyroid states in long-term DM2.
PMID- 28514544
TI - [Geriatric aspects in oncocoloproctology (review)].
AB - Severe comorbidity significantly limits the use of active surgical tactics in
patients of older age groups suffering from colorectal cancer (CRC), leading to
the abandonment of the necessary operations in 20 % of cases. The low use of
radical surgical tactics are not always related to objective difficulties, but
often can be due to the stereotypical approach to solving the question of the
treatment of the elderly patient, which leads to unreasonable refusal of surgical
intervention. Today is not defined by a single concept of surgical treatment of
patients with colon cancer in elderly and senile age. There is no universally
accepted system for determining the functional operability in this group of
patients, not developed specific algorithms for their preoperative preparation
and perioperative management. In this regard, the search for new approaches to
surgical treatment of geriatric patients with CRC, allowing, on the one hand, to
increase the percentage of completion radical surgery, and on the other, to
reduce the number of postoperative complications in this numerous group of
patients, is one of the priority tasks of Oncology.
PMID- 28514545
TI - [Diagnostics of the changes arising in an oral cavity at oncological sick senior
age groups (review)].
AB - Article is devoted to the changes happening in an oral cavity and in oral liquid
under the influence of preparations of the oncological diseases used for
treatment. Considering that research of oral liquid belongs to one of noninvasive
methods of diagnostics and can be used with success for definition and correction
of conditions of the mucous membrane of an oral cavity at the patients of
advanced and senile age passing polychemotherapeutic treatment, this type of
research is the extremely perspective for a gerontostomatology.
PMID- 28514546
TI - [Luzindol accelerates the aging of estrous function of female rats].
AB - In this paper, we investigated the dynamics of aging of the estrous function of
female rats kept in the conditions of standard vivarium lighting and receiving
luzindol - the blocker of melatonin receptors. Every three months, daily, for two
weeks, vaginal smears were taken from the animals and cytological examination of
the vaginal contents was conducted. Despite different mechanisms of the
development of melatonin system failure (a decreased production of melatonin and
a blockade of melatonin receptors), the effects of the influence on the ovulatory
function are similar. In case of the blockade of melatonin receptors, the
appearance of premature signs of aging of the reproductive function in rats was
observed. It was manifested by an increased duration of ovulatory cycle; a
decrease in the number of regular cycles; the emergence of irregular cycles; a
decrease in the number of short estrous cycles and an increase of long cycles;
the early development of persistent estrus.
PMID- 28514547
TI - [Evidence of feasibility etoricoxib therapy in osteoarthritis in elderly
patients].
AB - The article presents the results of a study of clinical efficacy in the treatment
of etorikoxib pain in patients with osteoarthritis of the knee and hip joints in
elderly patients. The study involved 296 patients with gonarthrosis and
coxarthrosis. It is shown that etoricoxib effectively relieves pain, has an
advantage over other NSAIDs speed and severity of the analgesic and anti
inflammatory effect, positive impact on laboratory signs of inflammation,
demonstrated good tolerability and a low incidence of side effects, does not
require discontinuation of therapy.
PMID- 28514548
TI - [The effect of vascular peptide bioregulator on the microcirculation in the brain
cortex of old rats].
AB - Using a TV device to study brain microcirculation, we found that after a course
of vascular peptide bioregulator the density of microvascular network of pia
matter of old rats (22-24 months) sensomotor cortex increased about 2,5-2,8 times
compared to control old rates; and noradrenaline-induced constriction reactions
and acetylcholine-induced dilative reactions of the pial arterioles increased
significantly. This perfusion in the tissue of the cerebral cortex is not
increased, but the degree of blood oxygen saturation in the microvasculature of
this tissue region raised.
PMID- 28514550
TI - [Screening tools for frailty in ambulatory care].
AB - The article gives a brief description of the frailty syndrome and comprehensive
geriatric assessment. We describe two classical models - a model of the phenotype
and the index of the frailty. The basic questionnaires for frailty syndrome
screening in outpatient practice, as well as research on the validation of these
questionnaires are presented. The results of comparative studies of
questionnaires for frailty screening are shown.
PMID- 28514549
TI - [Digoxin in elderly patients: therapeutic drug monitoring to increase the
efficiency of therapy (a review)].
AB - The focus of this review is on cardiac and non-cardiac effects of digoxin, a drug
used for treating the heart failure, and on link between these effects and the
serum digoxin concentration (SDC) in different dosing regimens. Elderly patients
are at the spotlight, as they are both at high risk and high potential benefit
from digoxin therapy, explaining potential usefulness from SDC monitoring in this
cohort of patients. The laboratory and clinical approaches used to prevent
digitalis intoxication are reviewed, with regard to their fidelity, clinical
value, and practical usefulness. The role of endogenous cardiotonic steroids,
sharing structural and functional similarity to digoxin and affecting the
diagnostic value of laboratory tests, is also discussed.
PMID- 28514551
TI - [Kidney function at patients of advanced and senile age before and in 24, 48, 120
hours after carrying out X-ray endovascular intervention].
AB - Research of a functional condition of kidneys at patients of advanced and senile
age before and in 24, 48, 120 hours after carrying out X-ray endovascular
intervention. Patients of age groups are examined: 34-59 years (49,7+/-7,8) - 35
people (group of control), 60-74 years (66,1+/-4,1) - 48 people and 75-82 years
(78,8+/-4,2) - 22 people. Sonclusion: it is confirmed the fact that at patients
of advanced and senile age dynamic control of a functional condition of kidneys
after 1st, 3rd and 5th days and till 3 weeks after carrying out X-ray
endovascular interventions is necessary.
PMID- 28514553
TI - [Significance of insulin resistance in the pathogenesis of sarcopenia and chronic
heart failure in elderly hypertensive patients].
AB - To determine the pathogenic role of insulin resistance in the formation of
involutive sarcopenia and chronic heart failure (CHF) were examined 88 elderly
patients with arterial hypertension (AH) and 32 elderly patients without
cardiovascular disease by methods of carbohydrate metabolism and the level of
brain natriuretic peptide precursor evaluation, muscle mass and strength
measuring, echocardiography, 6 minute walking test. It was found that in the
group of hypertensive patients with low mass and muscle strength significantly
increased indices of insulin resistance and more expressed signs of the left
ventricle myocardial dysfunction and functional class of heart failure, probably
as a result of disorders of energy homeostasis, resulting from the deterioration
of glucose into the muscle cells of the heart and skeletal muscles.
PMID- 28514552
TI - [Features of the periodontal pathology at patients with metabolic syndrome].
AB - The purpose of this article is to familiarize readers on the relationship between
metabolic syndrome and periodontitis, as well as common pathogenetic processes
underlying these diseases. The data of modern researches, devoted to the
correlation of lesions of periodontal and systemic diseases associated with
metabolic syndrome. In the article analyzed also the data of the original study
of the interaction of periodontitis and metabolic syndrome, which also used
special methods of examination like Doppler ultrasound microcirculatory
vasculature of the periodontal tissues and ultrasound densitometry. The possible
methods of diagnostics of a condition of periodontal tissues in patients with
metabolic syndrome are considered. Conclusions about the relationship of each
component of metabolic syndrome with periodontitis are made.
PMID- 28514554
TI - [Self-consciousness in elderly persons with cognitive impairment and vascular
dementia].
AB - Self-consciousness was compared in 17 elderly (aged 65-89 years old) persons with
cognitive impairment without dementia and 17 patients with vascular dementia.
Neurocognitive functions and mental health complaints were evaluated.
Neuropsychological assessment included evaluation of higher psychological
functions, such as attention, memory, conceptualization, gnosis (optic,
acoustic), manual skill, speech. Older persons with cognitive impairment assessed
their neurocognitive functions adequately. Patients with vascular dementia
usually denied cognitive deficit or explained it as a result of aging. Regardless
of physical health, older persons with cognitive impairment have active attitude
to aging. They could find ways of compensation of cognitive deficits without
assistance. Patients with vascular dementia could not compensate their cognitive
deficit even with support.
PMID- 28514555
TI - [The use of the gender dimorphism index of J. Tanner for assessing the physical
state of older women].
AB - Assessment of the physical status of older women conducted anthropometry and
bioimpendance analysis. Body type determined by the gender dimorphism index of J.
Tanner (1951). It was found that in the studied sample representative of
gynecomorphic and mesomorphic body types were determined in a high percentage of
cases: 46,15 and 49,11 %. Women andromorphic body type were found less frequently
- 4,74 %. Women with gynecomorphic body type were smaller mass and transverse
dimensions of the body, unlike representatives with andromorphic and
gynecomorphic body types. The absolute content of fat and lean body mass tended
to increase from gynecomorphic body types representatives to andromorphic. The
results of anthropometric measurements, bioimpedance analysis and determined by
the gender dimorphism index of J. Tanner provide results about adaptive
possibilities the human body and can serve as markers (predictors) of somatic
diseases.
PMID- 28514556
TI - [The syndrome of falls in the elderly].
AB - The purpose of the study was to examine the problem of falls in the elderly. A
prospective cohort study of 537 patients over 65 years using validated
questionnaires and functional tests. 56,58 % of patients had at least one fall
event in the 12 months prior to the observation. 82,76 % of all falls are over
the age of 85 years. Significantly more patients younger than 85 years fell in
the autumn and winter (to 17,64 and 25,93 %, respectively) and over the age of 85
years in 50 % of cases (95 % CI 28,2-71,8) fell summer. Polypharmacy and comorbid
conditions increases the risk of falls. 32,89 % of people over 65 years in the
fall received fractures. However, a fracture of the femoral neck in 60 % of cases
diagnosed over the age of 85 years. Hypodynamy observed in 69,77 % of cases.
PMID- 28514557
TI - [Systemic analysis of factors affecting the quality of life of elderly people
using different forms of social services].
AB - The satisfaction of the quality of life (QOL) in elderly age is discussed. There
have been considered the satisfaction of QOL depending on the form of social
service in urban and rural areas. The key factors influencing the QOL in various
forms of services is defined. They include: rural life satisfaction is largely
dependent on the availability of family than on the health and financial status;
in a special house for single elderly life satisfaction is determined only by the
state of health due to the large number of chronic diseases, in stationary social
services very important factor is loneliness, isolation that creates some feeling
of being tired of life, depression, provocation the abuse of alcohol.
PMID- 28514558
TI - [Aging-induced differences in relationships between intelligence and self
assessment of quality of life].
AB - Relationships between a self-assessment of quality of life and level of verbal,
figurative and social intelligence in three age groups of students (middle age
63,9+/-5,8, 32+/-7,2, and 19,7+/-1,5 years; 90 % women) are studied. The group of
elderly people differed from younger in low values of an integrated indicator
physical health according to SF-36 questionnaire, especially - on scales physical
and role functioning, and decreased figurative and social intelligence at
relative constancy of verbal IQ. The different age-associated forms of
interrelation of components of intelligence and quality of life are found:
positive correlation between social intelligence and role functioning scores at
senior persons; more numerous positive correlations between verbal and figurative
intelligence and indicators of quality of life including integrated indicator of
mental health in the thirty-year-old group; and positive correlation between
verbal intelligence and values on a scale physical functioning, but negative
correlations between figurative intelligence and role functioning and between
social intelligence and an integrated indicator physical health for the twenty
year-old group. Therefore, continuous education and IQ increasing during
professional activity and after retirement it is possible to consider as
prognostic valuable factors of "successful" aging.
PMID- 28514560
TI - [Organization of beds nursing care as a form of implementation of a comprehensive
strategy for health and social care elderly people].
AB - The article tells about one of the actual problem of the provision of medical and
social care for elderly and old aged people, through the organization of nursing
care beds in the Voronezh region. Since the beginning of 2014 there were
organized 320 such beds in 27 medical organizations of the region. Regular
surveys of patients and their relatives, as well as personnel involved in the
care service, made it possible to make the necessary adjustments and the further
expansion of services in other hospitals. Thus the end of 2014 the number of
nursing beds has been increased to 525, so more than a thousand patients have
received the necessary nursing care.
PMID- 28514559
TI - [Quality of life for men of different ages in the russian European North and its
relationship with self-reported health and hormonal status].
AB - Assessment of the quality of life for male inhabitants of the Russian European
North demonstrated decreased indices of physical health component (the scale of
role functioning determined by physical condition) and mental health component
(the scales of social functioning and role functioning determined by emotional
state and mental health) compared to the inhabitants of Siberia as a comparison
group. Men aged up to 29 had the highest values at all scales. The values
decreased with age. The most prominent decrease was observed for the scales of
general well-being and pain intensity. There was a moderate decrease for the
scales of physical functioning, role functioning determined by emotional state,
and role functioning determined by physical condition. Quality of life was
closely related to self-reported health of northerners, pathological index,
molecular marker of aging, and biological age. Negative correlation between these
values implies the deterioration of physical and mental health with biological
age. The quality of life for northerners also correlated with hormonal status.
There was a relationship between testosterone and three scales of physical health
components; between cortisol and one scale of physical component; and between
both dehydroepiandrosterone sulfate and insulin and the scales of physical and
mental components of health. The effect of various hormones on different age
groups of northerners was demonstrated.
PMID- 28514561
TI - [Changing health, activity and mood Department of day care clients comprehensive
social service center: training program, methods, results].
AB - The comparative analysis of changes in the self-assessment of health, activity
and mood of older clients (men and women) separating the daycare center of the
complex of social services. Used psychodiagnostic method of self-assessment of
the functional state of the differential "Test SAN" (V.A.Doskin, N.A. Lavrentiev,
V.B.Sphere, M.P.Miroshnikov). The study of these states conducted before and
after the implementation of targeted training programs, simulation and which goal
setting made from the standpoint of the system and subject-activity approach.
PMID- 28514562
TI - [Actual problems of social gerontology at the present stage of development of
Russia].
AB - The basic medico-demographic indices of aging population for Russia were
identified in this article. Special attention was given to the examination of the
demographic risks of a reduction in the population at the working ages, to an
increase in the demographic load on the labor forces. The "Strategy for Action
for the elderly persons until 2025", prepared by the Interdepartmental Working
Group at the Ministry of Labour and Social Protection of the Russian Federation,
was analyzed. The development and implementation of the professional longevity
management system is one of the timely and comprehensive solutions to the problem
of employment in the elderly. The need for further studies was proven, dedicated
to the use of innovative gerontotechnologies in order to prevent the premature
workability reduction, retarding of the aging processes, the level of mortality
decrease and the professional longevity increase, especially in the elderly.
PMID- 28514563
TI - Recent Trends in Kidney Transplant in the United States.
AB - The number of new wait list registrants has increased in the last decade but not
to the same magnitude as the increase in the number of end stage renal disease
patients in the United States. The number of wait list patients has increased at
a much higher pace due to the lack of kidney supply. The overall number of kidney
transplants only increased slightly. Paired exchange kidney transplant is a
viable source of increasing the availability of kidney transplant and also offers
access to transplant to patients with immunologic barriers to their intended
donors. Paired donor exchange results in similar outcomes despite recipients'
having a higher immunologic risk profile. The kidney allocation system (KAS) was
recently implemented and so far has resulted in more access for patients with
very high immunologic risk and allocation of lower kidney donor profile index
organs to younger recipients. Longer follow up is needed to determine the net
benefit of the KAS.
PMID- 28514564
TI - MELD Exceptions for Hepatocellular Carcinoma: Regional Variations in the Impact
of the Share 35 Liver Allocation Policy.
AB - Historically, the OPTN liver allocation policies have favored candidates listed
with MELD exception scores, and the use of exceptions has increased each year
since the inception of the MELD era. The implementation of Share 35 and other
recent changes in OPTN liver allocation policies have reduced the preference for
MELD exception candidates to some extent, but the nature and degree of the impact
appears to vary widely from one region to another. This report emphasizes the
geographic inequities and regional variations in transplant practices, with a
focus on liver transplant candidates with hepatocellular carcinoma exceptions,
and highlights the need for strategies to promote equitable organ distribution
across geographical regions and patient conditions.
PMID- 28514565
TI - An Update on Cardiac Transplantation in the United States Based on an Analysis of
the UNOS Registry.
AB - Cardiac transplantation remains a viable option for those with end-stage heart
disease. In the last few years, the number of heart transplants has begun to
increase slightly. Over the last 27 years, the major reasons for cardiac
transplant remain coronary artery disease and dilated cardiomyopathy. Currently,
heart transplants have an average lifespan of 10.5 years. The main United Network
for Organ Sharing characteristics correlating with poor allograft survival
include repeat transplantation, ischemic time, post-transplant dialysis, and age
at the time of transplant. Data over the last two decades shows that late graft
survival continues to improve slightly. This is primarily a result of a decrease
in early graft failure. In heart transplant patients, we still need to find ways
to stop late (>1 year post-transplant) graft loss.
PMID- 28514566
TI - Long-Term Pancreas Allograft Survival in Simultaneous Pancreas-Kidney
Transplantation by Era.
AB - Data collected by the United Network for Organ Sharing from all approved United
States transplant programs were analyzed; the data included 20,290 adult diabetic
patients who received primary pancreas transplants between October 1987 and
December 2014. Simultaneous pancreas-kidney (SPK) transplantation has become the
major therapeutic option for diabetes patients. The number of SPKs per year has
not increased since 1999; it leveled off or decreased slightly each year.
Recipients in the most recent period, 2010-2014, were more likely than recipients
in any of the other periods to be non-white, older, male, to have had diabetes
longer, to have higher body mass indices; and in this group there were more donor
recipient human leukocyte antigen mismatches. Donors in the 2010-2014 period were
more likely to be younger and male and less likely to be white. Pancreas graft
survival rates were highest in the 2010-2014 period (one-year graft survival
89.7%) vs. those for 1987-1989 (74.6%), 1990- 1994 (77.5%), 1995-1999 (82.9%),
2000-2004 (84.4%), and 2005-2009 (85.5%); the five-year rates were 72.7% for 2010
14 vs. 60.0%, 64.3%, 69.0%, 70.9%, and 73.9% for the other periods, respectively.
There was no decreased risk of graft failure for recent-era transplants compared
with those of 1987-1989, except for those in 2005-2009. By year of transplant,
the adjusted hazard ratios [with 95% confidence intervals (CI)] for overall loss
of grafts surviving over one year in eras 1990-1994, 1995-1999, 2000-2004, 2005
2009, and 2010-2014 were, respectively, 0.85 (CI 0.66-1.09), 0.85 (CI 0.66-
1.09), 0.87 (CI 0.67-1.13), 0.71 (CI 0.54-0.93), and 0.86 (CI 0.64-1.15). Chronic
rejection caused 44.9% of graft losses between one and five years and 51.5% after
five years. There is a need for a means to identify early markers of chronic
rejection-and to control it-to improve long-term survival.
PMID- 28514567
TI - Impact of Diabetes Mellitus on Survival Outcome of Lung Transplant Recipients: An
Analysis of OPTN/UNOS Data.
AB - BACKGROUND: There are limited data on the outcome of diabetic lung recipients,
especially in those with new-onset diabetes after transplantation (NODAT).
METHODS: We studied prevalence of pre-transplant diabetes mellitus (PDM) and
cumulative incidence of NODAT in lung recipients using the Organ Procurement and
Transplantation Network /United Network for Organ Sharing database. Between 2004
and 2011, adult (>=18 years old) recipients transplanted with either first single
or double-lung were included. Those who lacked a diabetes record or received
multi-organ transplants were excluded. Patient survival were studied in
recipients who had functioning grafts for at least one year. Results: There were
10,226 recipients who had at least one diabetes record, the prevalence of PDM was
18.25% and the cumulative incidence of NODAT during the five years post
transplant was 39.43%. Of 9,117 recipients who had functioning grafts for at
least one year, adjusted hazard ratios (HR) of PDM and NODAT, compared to the
diabetes-free group, were 1.12 (p=0.048) and 1.12 (p=0.025), respectively.
Independent risk factors for mortality included the presence of rejection in the
one year, cytomegalovirus serology donor positive/recipient negative, and
recipient age >60 years. Among recipients with cystic fibrosis, there was no
statistical difference in mortality between diabetic recipients and the diabetes
free group. Compared to the diabetes-free group, the adjusted HRs for mortality
of PDM and NODAT in recipients without cystic fibrosis were 1.15 (p=0.031) and
1.14 (p=0.011), respectively. CONCLUSIONS: Diabetes was associated with mortality
in lung transplant recipients overall and in lung recipients without cystic
fibrosis. However, there was no association between diabetes and mortality in
lung recipients with cystic fibrosis.
PMID- 28514568
TI - The 25th Anniversary of the National Transplantation Pregnancy Registry.
AB - The National Transplantation Pregnancy Registry (NTPR) is a unique resource for
comprehensive information about parenthood after transplantation. To date, 1461
female solid organ transplant recipients with 2609 pregnancies and 879 male
recipients who fathered 1358 pregnancies have participated in the NTPR. Over the
first 25 years of the NTPR, pregnancy after transplantation has progressed from a
situation where termination was once advised, to a topic of pre-transplant
counselling with likelihood for success if established criteria are met.
Pregnancy after transplantation remains high-risk; it should be carefully
considered, planned, and monitored by a multidisciplinary health care team.
Pregnancy and maternal outcomes vary based on multiple factors, especially on the
type of organ transplanted and the pre-pregnancy graft function. As an open-ended
condition-based study, the NTPR accumulates a vast amount of data that is used
for comparisons that measure the reliability and benefits of treatments and for
developing state-of-the-art management guidelines based on a review of current
practices at participating transplant centers. NTPR data analyses have
contributed to quantifying issues surrounding post-transplant parenthood such as
location of the transplanted organ in proximity to the developing fetus, the
safety of various immunosuppressive regimens for pregnancy and fatherhood, the
teratogenicity of maternal exposure to mycophenolate during pregnancy, the
advisability and timing of planning a posttransplant pregnancy, the dosing of
medications during pregnancy, the incidence and treatment of comorbidities during
pregnancy, and the effect of in utero or breast milk exposure to
immunosuppressants on the developing child. As the face of transplantation
evolves, the NTPR will continue to collect and disseminate information to assist
recipients and their healthcare providers in making informed decisions about the
advisability of pregnancy and care for those who choose to become parents after a
solid organ transplant. To insure the continued success of our study, all
transplant centers and recipients are encouraged to contact the NTPR to report
any post-transplant pregnancy.
PMID- 28514569
TI - Hepatitis C and Human Immunodeficiency Virus Kidney Transplantation: The Mount
Sinai Experience.
AB - Mount Sinai Hospital in New York has a long history in the field of organ
transplantation. The first kidney transplant at Mount Sinai was performed in 1967
by the late Dr. Lewis Burrows and the first laparoscopic donor nephrectomy in New
York was performed at Mount Sinai in 1996. Over 3000 kidney transplantations have
been performed at Mount Sinai. In the early 1990s, the first hepatitis C virus
(HCV) positive patient at Mount Sinai underwent a kidney transplant and the first
kidney transplant in a patient with human immunodeficiency virus (HIV) in New
York was performed at Mount Sinai in 2001. In general, these patients have done
well after renal transplantation, with outcomes similar to those seen in non
infected patients. This chapter will describe the evolution of immunosuppressive
regimens in HCV positive and HIV positive patients, and will describe the
outcomes of kidney transplantation in these patients. Given the favorable
outcomes, it is reasonable to continue to offer renal transplantation as a
treatment for end stage renal disease patients with HCV and/or HIV.
PMID- 28514570
TI - Liver Transplant at the University of Pennsylvania 2015.
AB - : In this brief report, we summarize activity and trends in liver transplantation
within the Penn Liver Transplant Program, including total program activity,
recipient characteristics, waitlist time to transplant, graft and patient
survival, rate of retransplantation, and multi-organ transplantation activity, as
well as post-transplant hospital length of stay. RESULTS: Penn Transplant has
performed 2478 total adult liver transplants to date, consisting of 2382 deceased
donor liver transplants and 96 living-donor liver transplants. Recipient race is
approximately 70% white, 20% black, and 10% "other" races including Hispanic,
Asian, and American Indian/Alaskan Native. Non-cholestatic cirrhosis is the
leading indication for liver transplantation, accounting for more than half of
all cases throughout the selected time interval. Most patients are not
hospitalized at the time of transplantation, and there has been a reduction in
the number of patients hospitalized in the intensive care unit at the time of
transplant in the past five years. The median time to transplant is 13.2 months.
Hazard ratios (HRs) for graft failure after one month, one year, and three years
post-transplant were reported as: 0.54, 1.05, 1.01 (adult deceased donor) and
0.58, 0.57, 1.16 (adult living donor); HRs for patient survival were reported as:
0.44, 1.03, 1.04 (adult deceased donor) and 0.73, 0.74, 0.69 (adult living donor)
for the same time increments. Penn averaged a 2.3% retransplantation rate and a
total multi-organ transplant volume of 13. The mean length of hospital stay
following transplantation was 8.83 days. CONCLUSION: Our program activity data
mirrors trends that are seen in many of the established busy liver transplant
centers in the United States. There is greater recognition that liver
transplantation can be offered to a larger number of candidates who are diagnosed
with progressive liver failure of primary cancer in the setting of liver
cirrhosis, and there is an increase in donor organs from either extended criteria
cadaveric donors or living donors. Despite more complex candidate populations and
increased utilization of extended criteria donors, Penn's outcomes continue to be
excellent. We postulate that the future depends on an increase in organ
procurement organization activity, redesign of the national organ allocation
system, and expansion of living donor activity.
PMID- 28514571
TI - ISMETT: An International Collaboration on Organ Transplantation.
AB - The Institute of the Mediterranean for Transplantation and High Specialty
Therapies (ISMETT) is a multi-organ transplant and high specialty center located
in Palermo, Italy and managed by the University of Pittsburgh Medical Center.
Clinical transplant activity started in 1999 and, herein, we illustrate the
outcomes achieved over the past 15 years. In total, ISMETT has performed 997
liver transplants (83.9% adults, 16.1% pediatrics) with a significant percentage
of liver transplants from cadaver split livers (17%) and partial grafts from
living donors (11.5%). Among liver transplant recipients, the overall five-year
graft survival was 74.3% in the adult population and 79% in the pediatric
population. ISMETT has also performed 419 kidney transplants in total: 211 from
cadaveric donors (22 double), 176 from living donors, and 32 combined (19 with
liver, 11 with pancreas, and 2 with heart). The 5-year renal graft survival was
82.2% (cadaveric donor) and 92.2% (living donor). More recently, in 2005, ISMETT
started pancreas, lung, and heart transplant programs. In total, 16 pancreas
transplants have been performed, of which 12 were simultaneous pancreas-kidney
transplants, 1 was pancreas after kidney, and 3 were pancreas alone transplants.
One pancreatic islet transplant was also performed in a patient who had already
undergone kidney transplantation. Patient and pancreas graft survivals at 1 year
were 86.7% and 73.3%, respectively, and 80% and 73.3% at five years (pancreas
survival is defined as normoglycemia and insulin-independence). Lung transplant
has been performed in 133 patients (116 double and 17 single lung). Eleven were
pediatric (8% of all transplants). The 1-month, 1-year, and 5-year overall graft
survivals were, 93.8%, 81.4%, and 75.6%, respectively. Heart transplantation has
been performed in 133 adults (85% were male). Coronary artery disease and
cardiomyopathy were the leading underlying heart disease diagnoses leading to
transplant. Mechanical support (ventricular assist device or extracorporeal
membrane oxygenation) as a bridge to transplant was used in 18% of the heart
transplant cases. One-year heart graft survival was 83% and 5-year heart graft
survival was 81%.
PMID- 28514572
TI - Liver Transplantation in Groningen, The Netherlands: A Single Center Status
Report.
AB - The liver transplantation program of the University Medical Center Groningen in
the Netherlands was started in 1979, making it one of the first programs
worldwide. During the past 36 years, a total of 1478 liver transplantations have
been performed, 459 of which were in children. One of the first patients
transplanted in 1979 is still alive and is one of the longest surviving patients
after liver transplantation worldwide. During the last decade, an increasing
number of donation after circulatory death (DCD) donor livers have been accepted
for transplantation. Over 30% of the livers transplanted in Groningen come from
DCD donors. These livers have an increased risk of developing biliary
complications, such as non-anastomotic biliary strictures (NAS). One of the main
research topics in Groningen has been the pathogenesis and prevention of NAS. In
an attempt to reduce the incidence of NAS after liver transplantation, machine
perfusion technology has been developed as an alternative to the traditional
method of static cold storage. Researchers of the Groningen liver transplant team
were the first in the world to report a method of ex situ normothermic machine
perfusion of human donor livers. The efficacy and safety of various types of
machine perfusion are currently studied in both animal models and clinical
trials. A second line of research in Groningen focuses on alterations in the
blood coagulation system in patients with liver disease and undergoing liver
transplantation. Groningen researchers were the first to describe a 'rebalanced
state' of the coagulation system in patients with liver disease, making them
prone to both bleeding and thrombo-embolic complications. Clinicians and
researchers at the Groningen liver transplant program will continue to
collaborate with a shared focus and the aim to provide innovation and the highest
level of care to patients with endstage liver disease.
PMID- 28514573
TI - Pancreas Transplant at the University of Maryland.
AB - The characteristic of our diabetic population has been ever changing. No longer
are our Type 1 diabetics young and thin; they too suffer from the obesity
epidemic and now present later with the complications of diabetes (renal
dysfunction, hypoglycemic unawareness, vision loss, neuropathy, etc.). Even with
all of our medical and technological advances to combat diabetes, there are many
who are not very well controlled. We evaluated the pancreas transplant recipients
in the last three years at the University of Maryland to study the outcomes of
these older and higher body mass index (BMI) recipients, as well as the impact of
using older and higher BMI donors. We saw no difference in the survival of the
patient or the allograft of recipients who were older or had higher BMIs. We also
saw no difference in morbidity for these patients. There also was no difference
when using older or higher BMI donor organs, longer cold ischemic times,
different types of donors (donation after cardiac death versus brain dead
donors), or different types of organs (simultaneous pancreas kidney, pancreas
transplant alone, or pancreas after kidney). In reviewing our waitlist, our
patients range widely in age and BMI. As long as they are fit for surgery, we
will continue to transplant our ever growing population of older and obese
diabetics without any more adverse outcomes than occur in our normal weight and
younger patients.
PMID- 28514574
TI - A Single Center 11 Year Experience with 202 Pancreas Transplants in the New
Millennium: Evolving Trends.
AB - : Our single center experience with pancreas transplantation (PTx) over an 11+
year period is reviewed. METHODS: We retrospectively studied outcomes in 202
consecutive PTxs in 192 patients at our center. All patients received either
rabbit anti-thymocyte globulin (rATG) or alemtuzumab (Alem) induction with
tacrolimus/mycophenolate mofetil and tapered steroids or early withdrawal. 179
PTxs (89%) were performed with portal-enteric and 23 with systemic-enteric
drainage. RESULTS: From 11/01 to 3/13, we performed 162 simultaneous kidney-PTxs
(SKPT), 35 sequential PTxs after kidney, and 5 PTx alone (40 solitary PTxs, SPT).
186 PTxs (92%) were primary and 16 were pancreas retransplants. With a mean
follow-up of 5.5 years, overall patient (86% SKPT versus 87% SPT), kidney (74%
SKPT versus 80% SPT), and pancreas graft survival (both 65%) rates were
comparable. Causes of PTx loss were also similar between SKPT and SPT; the rates
of early thrombosis were 8.6% and 5%, respectively. Acute rejection rates were
similar between groups (SKPT 29% versus SPT 28%, p= not significant). A
randomized trial of Alem versus rATG induction in SKPT demonstrated lower rates
of acute rejection and infection in the Alem group. Consequently, Alem induction
has been used exclusively in all PTxs since 2009. Early steroid elimination has
been feasible in most patients. Surveillance PTx biopsy-directed
immunosuppression has contributed to equivalent long-term outcomes in SKPT and
SPT. Good results have been achieved in African-American patients and in patients
with a type 2 diabetes phenotype. CONCLUSIONS: Excellent 5-year outcomes
following PTx can be achieved as >86% of patients are alive, >87% of surviving
patients are dialysis-free, 80% of surviving patients remain insulin-free, and
88% of surviving patients have detectable C-peptide levels.
PMID- 28514575
TI - Alloantibodies in Organ Transplant: A Review of Data Published in 2015.
AB - In recent years, there have been multiple studies published on longitudinal and
retrospective analysis of anti-human leukocyte antigen (anti-HLA) antibodies. The
focus of these reports was to determine specific characteristics of the impact of
donor specific anti-HLA antibodies (DSA) in organ transplantation. There has been
a growing concern about DSA in a multitude of organ transplants. Research efforts
are attempting to gain a better understanding of DSA and possible treatment
implications for patients with DSA. In 2015, many studies confirm and expand upon
both the understanding of the humoral theory and the clinical applications of DSA
in transplantation. This review highlights some of these publications and their
contributions to the humoral theory of transplantation.
PMID- 28514576
TI - Advances in Transplantation: Editorial.
PMID- 28514577
TI - A Review of the Management of Pregnancy After Cardiac Transplantation.
AB - Success and advances in the management of all aspects of heart disease and heart
transplantation have allowed for normalcy in life, including the question as to
the possibility of pregnancy in transplantation. With the growing young adult
population undergoing heart transplant, pregnancy and transplantation have become
an issue of importance. Despite the fact that nearly 50 years have passed since
the first heart transplant, there remains to be little evidence in regard to
management of pregnant heart transplant recipients. Thus, this review will
address issues related to pregnancy in this patient population, such as
preconception counseling, timing and optimization for pregnancy post transplant,
immunosuppression, cardiac assessment, and management of pregnant heart
transplant recipients, as well as hemodynamic effects of pregnancy on the
transplanted heart. Based on the available literature from registrar data, case
reports and series, with careful planning, monitoring, and appropriate therapies,
pregnancy in heart transplantation is a viable option in select patients. To
optimize maternal and fetal outcomes, recommendations are included in this review
to minimize complications including rejection, graft dysfunction, maternal
diabetes and hypertension, as well as appropriate changes in immunosuppression.
PMID- 28514578
TI - Strategies to Improve Novel Drug Development in Kidney Transplantation Through
the Clinical Trials Process.
AB - Kidney transplantation has emerged as the preferred treatment for end-stage renal
disease. Despite excellent short-term outcomes with standard T-cell centric
immunosuppression, long-term outcomes have not improved. Indeed, approximately
5,000 renal allografts fail in the United States each year. Until recently, the
focus on causes for late graft failures was on calcineurin inhibitor toxicity and
the effects of primary co-morbid conditions (i.e., diabetes and hypertension) or
recurrent glomerular diseases. However, several recent studies have identified
donor-specific antibodies and chronic antibody-mediated rejection as the primary
causes of late allograft failures. This finding has resulted in a renaissance of
interest in the development of new agents focused on modifying B cells and
alloantibody responses. In 2015, the Food and Drug Administration (FDA) held a
conference of experts focused on delineating a path forward for developing a more
streamlined clinical trials process to obtain labeling for novel agents in
transplantation. The particular focus was on developing new drugs to deal with
desensitization and prevention and treatment of antibody-mediated rejection since
there are currently no approved drugs in this area. In this manuscript, we will
discuss each of these important issues in depth, with particular focus on how to
improve the clinical trials process to obtain FDA approval for new drugs that
would be of benefit to our patients. It is also encouraging that since the FDA
meeting, two new labeling trials have gone forward and one has already begun
patient entry.
PMID- 28514579
TI - Should We Be Performing More Pancreas Transplants?
AB - Pancreas transplantation can provide insulin independence, improved survival, and
improved quality of life for patients with diabetes mellitus. However, there has
been a steady decline in the number of pancreas transplants (either alone or with
a kidney) performed in the United States over the past decade. This decline has
occurred despite a steady increase in the number of diabetic patients with end
stage renal disease on the kidney transplant alone waiting list. This paper will
review the current status of pancreas transplantation, suggest possible
explanations for the declining numbers of transplants, highlight current gaps in
knowledge, and suggest possible future studies and developments aimed at
increasing the application of this effective therapy.
PMID- 28514580
TI - Advancing Liver Transplantation.
AB - Donor organ scarcity remains a major limitation in liver transplantation and
accounts for a great proportion of wait list mortality. As a result, over the
past decade, significant efforts have been made to increase the existing donor
pool. These efforts have, in part, resulted in greater use of liver allografts
following donation after cardiac death (DCD) along with suboptimal (so-called
marginal) and extended criteria donors. Improved understanding of the
pathophysiology underlying the inferior outcomes of the liver allografts procured
after circulatory arrest has not only resulted in better selection and management
of DCD donors, but has also helped in the development of mechanical perfusion
strategies. Currently, there is much excitement surrounding the clinical
applicability of both hypothermic and normothermic perfusion and the potential to
impact patient survival and allograft function. Attempts to decrease late
mortality following liver transplantation have focused on minimization of and use
of new immunosuppressive medications with specific aims of reducing losses as a
result of infection, malignancy, and renal failure. Lastly, there has been
increased emphasis on gaining a better understanding of liver immunology and
redefining the impact of antibody-mediated rejection on allograft function and
patient survival.
PMID- 28514581
TI - Advancing Histocompatibility Testing for Solid Organ Transplantation - What is
Needed? A Personal Opinion.
AB - The field of histocompatibility testing has seen significant changes and
advancements in the past quarter of a century. The introduction of polymerase
chain reaction amplification into routine human leukocyte antigen (HLA) typing
has informed us on the magnitude of polymorphism among HLA alleles. Solid phase
testing for antibodies has provided unparalleled insight into antibody
specificity and the role of antibody mediated rejection in transplant outcomes.
Herein, we provide a brief overview of advancements in the field that are
currently in progress. We also provide our own personal opinion on what is on the
horizon and the direction in which we think the field should progress.
PMID- 28514582
TI - There is a Road, No Simple Highway: Envisioning a Path to Better Long-Term Organ
Transplant Survival.
AB - The current half-life of a transplanted organ has not improved in a very long
time. Historical reports on the causes of allograft failure have pointed to a
plethora of contributing issues. However, in recent years, alloantibody-mediated
injury has emerged as the major cause of allograft loss. As such, one road to
advance transplant is to address this problem. There is a hope that new
treatments can minimize the impact of alloantibody-mediated injury just as T-cell
directed therapies developed over the last few decades have minimized the impact
of T-cell mediated rejection on allograft survival. However, these new therapies
are at least a few years away. While we are unsure how to treat alloantibodies,
we can certainly do a better job at preventing them. This review will discuss the
current data surrounding alloantibody-mediated injury and how prevention of
alloantibodies may be one way to advance transplantation.
PMID- 28514583
TI - Modernization of Chronic Allograft Injury Research: Better Biomarkers, Better
Studies, Better Outcomes.
AB - Despite dramatic improvements in acute rejection rates and short-term allograft
survival, long-term allograft survival remains unchanged in the modern era,
largely due to chronic allograft injury, a progressive disease that is common
across all solid organ transplantation but has no proven treatment. Studies of
novel diagnostic and therapeutic strategies for chronic allograft injury have
been relatively sparse, in part due to the time and expense required to conduct
traditional long-term clinical studies of a variably progressive disease. In this
article, we review the pathophysiology of chronic allograft injury, including
recent insights into key mechanisms of the disease. We discuss the barriers to
progress in chronic allograft injury research and present alternative approaches
to study design that could accelerate improvements in diagnosis, prevention, or
treatment of the disease. We integrate these approaches with emerging biomarkers
and surrogate endpoints into a model clinical study of chronic renal allograft
injury, providing a framework for modern study design in solid organ
transplantation.
PMID- 28514585
TI - Advancing Lung Transplantation.
AB - Lung transplantation rapidly evolved from an experimental to a conventional
therapy for patients with end-stage lung disease. In recent years, approximately
4,000 lung transplants are performed annually worldwide. A shortage of suitable
donor organs remains the main obstacle to increasing transplant volume. In
addition, long-term outcomes remain disappointing, and the median survival after
transplantation is approximately 6 years. Chronic rejection has clearly emerged
as the leading obstacle to better outcomes beyond the first year after
transplantation. This generally follows a progressive and relentless course
culminating in allograft failure and death. Consequently, there is a critical
need for strategies that delay or prevent the development of chronic rejection,
and better treatments that halt the progression of chronic rejection. The impact
of novel interventions is best assessed in the context of multi-center randomized
controlled trials.
PMID- 28514584
TI - Kidney Transplant Survival: Transforming Early Post-Transplant Opportunities to
Long-Term Success.
AB - Substantial strides have been made in improving the short-term success after
kidney transplantation. Although there has been some progress, there has not been
a robust improvement with respect to long-term outcomes. However, there remain
many potentially modifiable transplant-specific risks to long-term patient and
graft survival. In this chapter, we detail the current state of five important
short-term transplant-specific clinical events. The early post-transplant events
that negatively impact long-term survival discussed in this chapter are: acute T
cell mediated rejection, acute antibody mediated rejection, delayed graft
function, post-transplant viral infections, and recurrent and de novo diseases
after transplantation. This chapter focuses on unmet needs and outlines important
goals, specific to each of the topics, that hold promise for achieving better
long-term graft survival in kidney transplant patients. Consistent across all
five areas are: the need for better standardization and improvement in diagnosis
and testing, identification of relevant clinical surrogate markers in the design
of new studies, newer immunosuppressive agents, anti-viral agents and targeted
therapy for certain diseases, and innovative newer clinical trials. A
multifaceted approach will further enhance long-term kidney transplant survival.
PMID- 28514586
TI - BKV Viremia and Development of De Novo DSA in Renal Transplant Recipients.
AB - BK virus (BKV) viremia is a common complication of kidney transplantation. In
2008, we enacted a screening protocol to detect BKV infection at our institution.
The cumulative incidence of BKV viremia at our center is 24%, with most cases
being detected in the first year post-transplant. We have previously identified
the development of de novo donor specific antibody as a consequence of BKV
infection treated with immunosuppression reduction; in this report, we confirm
our prior findings and extend them to include an association of both Class I and
Class II antibodies with BKV viremia. While with a median time of 4 years follow
up there was no difference in patient or allograft survival on the basis of BKV
viremia. Identification of treatment strategies for BKV that will prevent
complications such as donor specific antibodies should be a research priority in
this area.
PMID- 28514587
TI - BK Virus After Kidney Transplantation: A Review of Screening and Treatment
Strategies and a Summary of the Massachusetts General Hospital Experience.
AB - BK virus (BKV) is a common infection encountered after kidney transplantation.
BKV is associated with a spectrum of manifestations, starting with sub-clinical
viruria, followed by viremia and BKV-associated nephropathy. Standard of care
includes routine post-transplant screening for BK viruria and/or viremia. Both
the Kidney Disease Improving Global Outcomes and the American Society of
Transplantation Infectious Diseases Community of Practice have published
screening recommendations. Although they vary slightly, they both highlight the
importance of early detection with serial screening. Once BK viremia is detected,
the standard management approach includes a reduction of immunosuppression.
Guidelines differ slightly about the sequence of the immunosuppression reduction,
but the end result is the same: lowering the overall immunosuppressive burden in
the patient with BKV infection. At the Massachusetts General Hospital, from 2007
to 2009, there was no BKV screening protocol in place. The rate of screening
during this time period increased from 62% to 81%. A total of 29 of the 243
patients were diagnosed with BK viremia (11.9%), with 23 identified as a result
of screening and 6 as a result of testing for graft dysfunction. We developed a
BKV screening protocol consisting of BKV polymerase chain reaction testing in
blood starting 2 months after kidney transplantation and every 2 months
thereafter, continuing through month 24 regardless of the allograft function.
Additional screening for 6 more months is performed in patients who receive anti
lymphocyte globulin for the treatment of acute rejection. Finally, all patients
with otherwise unexplained allograft dysfunction are screened. Currently, work is
being done investigating the use of mammalian target of rapamycin inhibitors to
treat BKV infection. Trials are also ongoing evaluating cell-based therapies for
BKV. Research to develop a vaccine or a direct-acting antiviral agent is in
critical need and an area of research that should be given high priority.
PMID- 28514588
TI - Immunologic and Infectious Complications in Highly Sensitized Patients Post
Kidney Transplantation.
AB - Desensitization therapies evolved more than a decade ago to deal with the growing
numbers of highly human leukocyte antigen sensitized patients who have an
immunologic barrier to successful transplantation. Two protocols have evolved and
have been adopted for primary desensitization. These include high dose
intravenous immune globulin (IVIG), plasma exchange + low doses IVIG +/-
rituximab. These protocols have been very successful and have extended and
improved the lives of numerous sensitized patients who would otherwise languish
on dialysis. Despite these successes, problems do exist with desensitization.
These include the risks for antibody-mediated rejection (ABMR) and infections
related to increased immunosuppression. Here, we discuss current and evolving
therapies for the prevention and treatment of ABMR. In addition, we discuss
current data regarding infection risks, especially BK virus, that may predispose
patients to development of de novo donor specific antibodies and antibody
rejection. Novel therapies will also be discussed.
PMID- 28514589
TI - Complications in Transplantation: Medication Nonadherence.
AB - Following solid organ transplant, complex, lifelong medication regimens are
required to prevent allograft rejection. Estimates of medication nonadherence in
transplant recipients vary and may be as high as 70%. Poor medication adherence
post transplant has been recognized as a contributing factor to reduced outcomes,
including rejection, graft loss, and survival. Despite the numerous identified
approaches for adherence assessment, there remains no gold standard. Ongoing
efforts to identify optimal immunosuppressant adherence monitoring and measuring
tools in an attempt to identify at risk populations post transplantation
continue; however, the link between this information and outcomes remains to be
discovered. Future adherence studies within the transplant population should
focus on developing surrogate markers of immunosuppressant therapy adequacy and
exploring the association amongst this data, adherence interventions, and
outcomes so that optimal strategies may be identified. Immunosuppressant
adherence should not be assumed, and interventions aimed a priori will provide
opportunities to derail the movement of negative health outcomes resulting from
preventable causes.
PMID- 28514590
TI - C1q Assay Results in Complement-Dependent Cytotoxicity Crossmatch Negative Renal
Transplant Candidates with Donor-Specific Antibodies: High Specificity But Low
Sensitivity When Predicting Flow Crossmatch.
AB - In complement dependent cytotoxicity crossmatch negative renal transplant
candidates with human leukocyte antigen donor-specific antibodies (DSA), both the
presence of DSA C1q+ and the dominant DSA fluorescence were significantly
associated with a positive flow cytometry crossmatch (FXM+). The C1q+ assay was
highly specific, but had low sensitivity when predicting FXM+, so the clinical
significance of a FXM+ in the absence of DSA C1q+ remains to be clarified in
future studies.
PMID- 28514591
TI - Risk Stratification of Human Leukocyte Antigen Class II Donor Specific Antibody
Positive Patients by Immunoglobulin G Subclasses.
AB - BACKGROUND: Human leukocyte antigen (HLA) antibodies are a major cause of graft
loss in mismatched transplant recipients. However, the time to graft loss
resulting from antibody induced injury is unpredictable. The unpredictable nature
of antibodies may be related to the subclass of antibodies. In this study, HLA
immunoglobulin G (IgG) subclasses were investigated to determine whether a unique
IgG subclass composition could better identify those patients at eminent risk for
graft loss. METHODS: The serial serum samples from the 57 patients with post
transplant HLA class II donor specific antibodies (DSA) were tested for the three
IgG subclasses (IgG1, IgG3, and IgG4). RESULTS: IgG3 and IgG4 were highly
prevalent in failed patients compared to functioning patients (82 % vs. 34%, 45%
vs. 20%, respectively). IgG3 development showed a distinct subclass trend between
failed and functioning patients with poor graft survival (log rank p=0.0006).
IgG1 was almost equally abundant in both groups (100% and 97%, respectively). Of
the 5 patterns of IgG subclass combinations observed, IgG1+3+ showed the
strongest association with graft failure (hazard ratio 3.14, p=0.007).
CONCLUSION: Patients with IgG3 subclass HLA DSA showed lower graft survival. Post
transplant monitoring for IgG subclasses rather than total IgG monitoring may
identify patients at risk for graft failure.
PMID- 28514592
TI - Soft Skyrmions, Spontaneous Valence and Selection Rules in Nanoparticle
Superlattices.
AB - A number of bewildering paradoxes arise in the field of nanoparticle self
assembly: nominal low density superlattices, strong stability of low coordination
sites, and a clear but imperfect correlation between lattice stability and the
maximum of hard sphere packing, despite the fact that that nanocrystals
themselves are, through their ligands, very much compressible. In this study, I
show that by regarding nanocrystals as pseudotopological objects ("soft
skyrmions"), it is possible to identify and classify the ligand textures that
determine their bonding. These textures consist of interacting vortices, where
the total vorticity defines a spontaneous valence (coordination). Furthermore,
skyrmion interactions are governed by two simple assumptions, which lead to a set
of selection rules for superlattice structure. Besides resolving all the above
paradoxes, the predictions are completely supported by more than one hundred
sixty experiments gathered from the literature, including a wide range of
nanocrystal cores and ligands (saturated or unsaturated hydrocarbons, amines,
polystyrene, etc.). How those results can be used for addressing more complex
structures and guiding future experiments is also addressed.
PMID- 28514593
TI - Thickness Resonance Acoustic Microscopy for Nanomechanical Subsurface Imaging.
AB - A nondestructive scanning near-field thickness resonance acoustic microscopy
(SNTRAM) has been developed that provides high-resolution mechanical depth
sensitivity and sharp phase contrast of subsurface features. In SNTRAM
technology, we excited the sample at its thickness resonance, at which a sharp
change in phase is observed and mapped with a scanning probe microscopy stage in
near field to provide nanometer-scale nanomechanical contrast of subsurface
features/defects. We reported here the remarkable subsubsurface phase contrast
and sensitivity of SNTRAM by exciting the sample with a sinusoidal elastic wave
at a frequency equal to the thickness resonance of the sample. This results in a
large shift in phase component associated with the bulk longitudinal wave
propagating through the sample thickness, thus suggesting the usefulness of this
method for (a) generating better image contrast due to high S/N of the
transmitted ultrasound wave to the other side of the sample and (b) sensitive
detection of local variation in material properties at much better resolution due
to the sharp change in phase. We demonstrated that the sample excited at the
thickness resonance has a more substantial phase contrast and depth sensitivity
than that excited at off-resonance and related acoustic techniques. Subsurface
features down to 5-8 nm lateral resolution have been demonstrated using a
standard sample.
PMID- 28514595
TI - Flocculation and Dewatering of Mature Fine Tailings Using Temperature-Responsive
Cationic Polymers.
AB - Temperature-responsive copolymer with cationic charge was prepared with N
isopropylacrylamide (NIPAm) and 2-aminoethyl methacrylamide hydrochloride (AEMA)
by conventional free-radical polymerization. The flocculation performance of the
copolymer, poly(AEMA-st-NIPAm), was compared to five different mixture ratios of
polyNIPAm and cationic poly(acrylamide-st-diallyldimethylammonium chloride)
(poly(AAm-st-DADMAC)). The effects of polymer mixture ratios, polymer dosages,
and temperature on solid-liquid separation as a function of initial settling
rates (ISR), supernatant turbidity, sediment solid content, and water recovery
were investigated. Poly(NIPAm) can facilitate particles aggregation by bridging
and hydrogen bonding under lower critical solution temperature (LCST); whereas,
at temperature above LCST, the adsorption of poly(NIPAm) chains on particles can
be enhanced by hydrophobic interaction. A two-step (25 degrees C -> 50 degrees
C -> 25 degrees C) consolidation can further enhance the sediment solid content
by polyNIPAm. While the neutral property of polyNIPAm resulted in high turbidity
of supernatant, mixing with poly(AAm-st-DADMAC) increases the clarity of
supernatant by neutralization of fine particles. The copolymer poly(AEMA-st
NIPAm) functions as a polyelectrolyte to enhance the polymer adsorption onto
particles via electrostatic interactions, thus further improving ISR and
supernatant clarity.
PMID- 28514594
TI - Quantum Monte Carlo Calculations on a Benchmark Molecule-Metal Surface Reaction:
H2 + Cu(111).
AB - Accurate modeling of heterogeneous catalysis requires the availability of highly
accurate potential energy surfaces. Within density functional theory, these can
unfortunately-depend heavily on the exchange-correlation functional. High-level
ab initio calculations, on the other hand, are challenging due to the system size
and the metallic character of the metal slab. Here, we present a quantum Monte
Carlo (QMC) study for the benchmark system H2 + Cu(111), focusing on the
dissociative chemisorption barrier height. These computationally extremely
challenging ab initio calculations agree to within 1.6 +/- 1.0 kcal/mol with a
chemically accurate semiempirical value. Remaining errors, such as time-step
errors and locality errors, are analyzed in detail in order to assess the
reliability of the results. The benchmark studies presented here are at the
cutting edge of what is computationally feasible at the present time.
Illustrating not only the achievable accuracy but also the challenges arising
within QMC in such a calculation, our study presents a clear picture of where we
stand at the moment and which approaches might allow for even more accurate
results in the future.
PMID- 28514596
TI - Unraveling the Growth Mechanism of Silica Particles in the Stober Method: In Situ
Seeded Growth Model.
AB - In this work, we investigated the kinetic balance between ammonia-catalyzed
hydrolysis of tetraethyl orthosilicate (TEOS) and subsequent condensation over
the growth of silica particles in the Stober method. Our results reveal that, at
the initial stage, the reaction is dictated by TEOS hydrolysis to form silanol
monomers, which is denoted as pathway I and is responsible for nucleation and
growth of small silica particles via condensation of neighboring silanol monomers
and siloxane network clusters derived thereafter. Afterward, the reaction is
dictated by condensation of newly formed silanol monomers onto the earlier formed
silica particles, which is denoted as pathway II and is responsible for the
enlargement in size of silica particles. When TEOS hydrolysis is significantly
promoted, either at high ammonia concentration (>=0.95 M) or at low ammonia
concentration in the presence of LiOH as secondary catalyst, temporal separation
of pathways I and II makes the Stober method reminiscent of in situ seeded
growth. This knowledge advance enables us not only to reconcile the most
prevailing aggregation-only and monomer-addition models in literature into one
consistent framework to interpret the Stober process but also to grow
monodisperse silica particles with sizes in the range 15-230 nm simply but
precisely regulated by the ammonia concentration with the aid of LiOH.
PMID- 28514597
TI - A Blocked Linear Method for Optimizing Large Parameter Sets in Variational Monte
Carlo.
AB - We present a modification to variational Monte Carlo's linear method optimization
scheme that addresses a critical memory bottleneck while maintaining
compatibility with both the traditional ground state variational principle and
our recently introduced variational principle for excited states. For wave
function ansatzes with tens of thousands of variables, our modification reduces
the required memory per parallel process from tens of gigabytes to hundreds of
megabytes, making the methodology a much better fit for modern supercomputer
architectures in which data communication and per-process memory consumption are
primary concerns. We verify the efficacy of the new optimization scheme in small
molecule tests involving both the Hilbert space Jastrow antisymmetric geminal
power ansatz and real space multi-Slater Jastrow expansions. Satisfied with its
performance, we have added the optimizer to the QMCPACK software package, with
which we test a systematically convergent, nonperturbative approach to excitation
energies on the example of a Mott-insulating hydrogen ring.
PMID- 28514598
TI - The communal relation of MTHFR, MTR, ACE gene polymorphisms and
hyperhomocysteinemia as conceivable risk of coronary artery disease.
AB - Homocysteine and its modulating genes have strongly emerged as novel biomarkers
for coronary artery disease (CAD). In the present study, we investigated whether
polymorphisms in homocysteine pathway genes and the plasma levels of
homocysteine, folate, and vitamin B12, independently or in combination, are
associated with CAD risk. A total of 504 participants were recruited (cases, n =
254; controls, n = 250, respectively). Tetra primer allele refractory mutation
system polymerase chain reaction (PCR) was used for resolving the genotypes of
5'10' methylenetetrahydrofolate reductase 'MTHFR' polymorphisms (rs1801133,
rs1801131), 5' methyl tetrahydrofolate homocysteine methyltransferase 'MTR'
polymorphism (rs1805087), paroxanse1 'PON1' polymorphism (rs662), and
cystathionine beta synthase 'CBS' polymorphism (rs5742905). Conventional PCR
amplification was carried out for resolving angiotensin converting enzyme 'ACE'
insertion/deletion (I/D) polymorphism (rs4646994). ANOVA analysis, adjusted for
the covariates, revealed that rs1801133, rs1805087 polymorphisms and homocysteine
levels were associated with CAD. Logistic regression analysis (adjusted) revealed
similar findings. Logistic regression analysis after applying factorial design to
the studied single nucleotide polymorphisms (SNPs) revealed that homocysteine
levels and heterozygous and mutant alleles at rs1801133, rs1805087, along with
mutant alleles at rs1801131, rs4646994, conferred higher risk for CAD. Our
results provide insight into the multifactorial nature of coronary artery
disease. We highlight that SNPs in folate pathway genes and homocysteine have
role in disease causation and can be used in disease prediction strategies.
PMID- 28514599
TI - A bioenergetics systems evaluation of ketogenic diet liver effects.
AB - Ketogenic diets induce hepatocyte fatty acid oxidation and ketone body
production. To further evaluate how ketogenic diets affect hepatocyte
bioenergetic infrastructure, we analyzed livers from C57Bl/6J male mice
maintained for 1 month on a ketogenic or standard chow diet. Compared with the
standard diet, the ketogenic diet increased cytosolic and mitochondrial protein
acetylation and also altered protein succinylation patterns. SIRT3 protein
decreased while SIRT5 protein increased, and gluconeogenesis, oxidative
phosphorylation, and mitochondrial biogenesis pathway proteins were variably and
likely strategically altered. The pattern of changes observed can be used to
inform a broader systems overview of how ketogenic diets affect liver
bioenergetics.
PMID- 28514600
TI - Evaluating five different loci (rbcL, rpoB, rpoC1, matK, and ITS) for DNA
barcoding of Indian orchids.
AB - Orchidaceae, one of the largest families of angiosperms, is represented in India
by 1600 species distributed in diverse habitats. Orchids are in high demand owing
to their beautiful flowers and therapeutic properties. Overexploitation and
habitat destruction have made many orchid species endangered. In the absence of
effective identification methods, illicit trade of orchids continues unabated.
Considering DNA barcoding as a potential identification tool, species
discrimination capability of five loci, ITS, matK, rbcL, rpoB, and rpoC1, was
tested in 393 accessions of 94 Indian orchid species belonging to 47 genera,
including one listed in Appendix I of CITES and 26 medicinal species. ITS
provided the highest species discrimination rate of 94.9%. While, among the
chloroplast loci, matK provided the highest species discrimination rate of 85.7%.
None of the tested loci individually discriminated 100% of the species.
Therefore, multi-locus combinations of up to five loci were tested for their
species resolution capability. Among two-locus combinations, the maximum species
resolution (86.7%) was provided by ITS+matK. ITS and matK sequences of the
medicinal orchids were species specific, thus providing unique molecular
identification tags for their identification and detection. These observations
emphasize the need for the inclusion of ITS in the core barcode for plants,
whenever required and available.
PMID- 28514602
TI - Informed Consent.
PMID- 28514603
TI - Case 15-2017 - A 27-Year-Old Woman with Anemia, Thrombocytosis, and Skin Lesions
after Travel Abroad.
PMID- 28514605
TI - Physiological Effects of Chronic Hypoxia.
PMID- 28514606
TI - IDH2 Mutation in a Patient with Metastatic Colon Cancer.
PMID- 28514607
TI - Tuberous Sclerosis Complex.
PMID- 28514608
TI - The Committed Perspective - Policy Principles for Regional Health Plans.
PMID- 28514601
TI - Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis.
AB - BACKGROUND: Eosinophilic granulomatosis with polyangiitis is an eosinophilic
vasculitis. Mepolizumab, an anti-interleukin-5 monoclonal antibody, reduces blood
eosinophil counts and may have value in the treatment of eosinophilic
granulomatosis with polyangiitis. METHODS: In this multicenter, double-blind,
parallel-group, phase 3 trial, we randomly assigned participants with relapsing
or refractory eosinophilic granulomatosis with polyangiitis who had received
treatment for at least 4 weeks and were taking a stable prednisolone or
prednisone dose to receive 300 mg of mepolizumab or placebo, administered
subcutaneously every 4 weeks, plus standard care, for 52 weeks. The two primary
end points were the accrued weeks of remission over a 52-week period, according
to categorical quantification, and the proportion of participants in remission at
both week 36 and week 48. Secondary end points included the time to first relapse
and the average daily glucocorticoid dose (during weeks 48 through 52). The
annualized relapse rate and safety were assessed. RESULTS: A total of 136
participants underwent randomization, with 68 participants assigned to receive
mepolizumab and 68 to receive placebo. Mepolizumab treatment led to significantly
more accrued weeks of remission than placebo (28% vs. 3% of the participants had
>=24 weeks of accrued remission; odds ratio, 5.91; 95% confidence interval [CI],
2.68 to 13.03; P<0.001) and a higher percentage of participants in remission at
both week 36 and week 48 (32% vs. 3%; odds ratio, 16.74; 95% CI, 3.61 to 77.56;
P<0.001). Remission did not occur in 47% of the participants in the mepolizumab
group versus 81% of those in the placebo group. The annualized relapse rate was
1.14 in the mepolizumab group, as compared with 2.27 in the placebo group (rate
ratio, 0.50; 95% CI, 0.36 to 0.70; P<0.001). A total of 44% of the participants
in the mepolizumab group, as compared with 7% of those in the placebo group, had
an average daily dose of prednisolone or prednisone of 4.0 mg or less per day
during weeks 48 through 52 (odds ratio, 0.20; 95% CI, 0.09 to 0.41; P<0.001). The
safety profile of mepolizumab was similar to that observed in previous studies.
CONCLUSIONS: In participants with eosinophilic granulomatosis with polyangiitis,
mepolizumab resulted in significantly more weeks in remission and a higher
proportion of participants in remission than did placebo, thus allowing for
reduced glucocorticoid use. Even so, only approximately half the participants
treated with mepolizumab had protocol-defined remission. (Funded by
GlaxoSmithKline and the National Institute of Allergy and Infectious Diseases;
ClinicalTrials.gov number, NCT02020889 .).
PMID- 28514609
TI - Letter to a Young Female Physician.
PMID- 28514610
TI - Osimertinib in EGFR T790M-Positive Lung Cancer.
PMID- 28514611
TI - Osimertinib in EGFR T790M-Positive Lung Cancer.
PMID- 28514612
TI - Reversal of Autoimmune Toxicity and Loss of Tumor Response by Interleukin-17
Blockade.
PMID- 28514614
TI - Bariatric Surgery or Intensive Medical Therapy for Diabetes after 5 Years.
PMID- 28514615
TI - Bariatric Surgery or Intensive Medical Therapy for Diabetes after 5 Years.
PMID- 28514613
TI - KIT Inhibition by Imatinib in Patients with Severe Refractory Asthma.
AB - BACKGROUND: Mast cells are present in the airways of patients who have severe
asthma despite glucocorticoid treatment; these cells are associated with disease
characteristics including poor quality of life and inadequate asthma control.
Stem cell factor and its receptor, KIT, are central to mast-cell homeostasis. We
conducted a proof-of-principle trial to evaluate the effect of imatinib, a KIT
inhibitor, on airway hyperresponsiveness, a physiological marker of severe
asthma, as well as on airway mast-cell numbers and activation in patients with
severe asthma. METHODS: We conducted a randomized, double-blind, placebo
controlled, 24-week trial of imatinib in patients with poorly controlled severe
asthma who had airway hyperresponsiveness despite receiving maximal medical
therapy. The primary end point was the change in airway hyperresponsiveness,
measured as the concentration of methacholine required to decrease the forced
expiratory volume in 1 second by 20% (PC20). Patients also underwent
bronchoscopy. RESULTS: Among the 62 patients who underwent randomization,
imatinib treatment reduced airway hyperresponsiveness to a greater extent than
did placebo. At 6 months, the methacholine PC20 increased by a mean (+/-SD) of
1.73+/-0.60 doubling doses in the imatinib group, as compared with 1.07+/-0.60
doubling doses in the placebo group (P=0.048). Imatinib also reduced levels of
serum tryptase, a marker of mast-cell activation, to a greater extent than did
placebo (decrease of 2.02+/-2.32 vs. 0.56+/-1.39 ng per milliliter, P=0.02).
Airway mast-cell counts declined in both groups. Muscle cramps and
hypophosphatemia were more common in the imatinib group than in the placebo
group. CONCLUSIONS: In patients with severe asthma, imatinib decreased airway
hyperresponsiveness, mast-cell counts, and tryptase release. These results
suggest that KIT-dependent processes and mast cells contribute to the
pathobiologic basis of severe asthma. (Funded by the National Institutes of
Health and others; ClinicalTrials.gov number, NCT01097694 .).
PMID- 28514616
TI - Bariatric Surgery or Intensive Medical Therapy for Diabetes after 5 Years.
PMID- 28514617
TI - Scarlet Fever.
PMID- 28514619
TI - Targeting Eosinophils in Eosinophilic Granulomatosis with Polyangiitis.
PMID- 28514618
TI - Aerobic or Resistance Exercise, or Both, in Dieting Obese Older Adults.
AB - BACKGROUND: Obesity causes frailty in older adults; however, weight loss might
accelerate age-related loss of muscle and bone mass and resultant sarcopenia and
osteopenia. METHODS: In this clinical trial involving 160 obese older adults, we
evaluated the effectiveness of several exercise modes in reversing frailty and
preventing reduction in muscle and bone mass induced by weight loss. Participants
were randomly assigned to a weight-management program plus one of three exercise
programs - aerobic training, resistance training, or combined aerobic and
resistance training - or to a control group (no weight-management or exercise
program). The primary outcome was the change in Physical Performance Test score
from baseline to 6 months (scores range from 0 to 36 points; higher scores
indicate better performance). Secondary outcomes included changes in other
frailty measures, body composition, bone mineral density, and physical functions.
RESULTS: A total of 141 participants completed the study. The Physical
Performance Test score increased more in the combination group than in the
aerobic and resistance groups (27.9 to 33.4 points [21% increase] vs. 29.3 to
33.2 points [14% increase] and 28.8 to 32.7 points [14% increase], respectively;
P=0.01 and P=0.02 after Bonferroni correction); the scores increased more in all
exercise groups than in the control group (P<0.001 for between-group
comparisons). Peak oxygen consumption (milliliters per kilogram of body weight
per minute) increased more in the combination and aerobic groups (17.2 to 20.3
[17% increase] and 17.6 to 20.9 [18% increase], respectively) than in the
resistance group (17.0 to 18.3 [8% increase]) (P<0.001 for both comparisons).
Strength increased more in the combination and resistance groups (272 to 320 kg
[18% increase] and 288 to 337 kg [19% increase], respectively) than in the
aerobic group (265 to 270 kg [4% increase]) (P<0.001 for both comparisons). Body
weight decreased by 9% in all exercise groups but did not change significantly in
the control group. Lean mass decreased less in the combination and resistance
groups than in the aerobic group (56.5 to 54.8 kg [3% decrease] and 58.1 to 57.1
kg [2% decrease], respectively, vs. 55.0 to 52.3 kg [5% decrease]), as did bone
mineral density at the total hip (grams per square centimeter; 1.010 to 0.996 [1%
decrease] and 1.047 to 1.041 [0.5% decrease], respectively, vs. 1.018 to 0.991
[3% decrease]) (P<0.05 for all comparisons). Exercise-related adverse events
included musculoskeletal injuries. CONCLUSIONS: Of the methods tested, weight
loss plus combined aerobic and resistance exercise was the most effective in
improving functional status of obese older adults. (Funded by the National
Institutes of Health; LITOE ClinicalTrials.gov number, NCT01065636 .).
PMID- 28514620
TI - Registry-Based Surveillance of Medical-Device Safety.
PMID- 28514621
TI - Registry-Based Surveillance of Medical-Device Safety.
PMID- 28514622
TI - Mast Cells and KIT as Potential Therapeutic Targets in Severe Asthma.
PMID- 28514623
TI - A 21st-Century Health IT System - Creating a Real-World Information Economy.
PMID- 28514626
TI - Influence of Early Reproductive Success on Longevity and Late Reproductive
Success in an Alpine Ungulate.
AB - The life-history theories of aging predict lifetime trade-offs between early
reproductive allocation and late-life survival, reproduction, or both components
of fitness. Recent studies in wild populations have found evidence for these
early-late life trade-offs, but rarely have they been found across multiple
traits while exploring the additional effects of variation in environmental
conditions and individual quality. Benefiting from longitudinal data on adult
female mountain goats (Oreamnos americanus), we investigated the influence of age
at first reproduction (AFR) and early reproductive success (ERS) on longevity,
late reproductive success, and senescence rates while accounting for the
influence of natal environmental conditions and individual quality. Contrary to
predictions, we did not find evidence for early-late life trade-offs. Instead, an
earlier AFR and a greater ERS had positive but weak direct effects on late
reproductive success. Natal population density, however, was the strongest
determinant of all life-history traits, having a direct negative effect on female
longevity, late reproductive success, AFR, and ERS. Although natal density
reduced the probability of annual reproduction and annual survival during
adulthood, higher allocation to reproduction in early life and poorer natal
conditions did not lead to accelerated rates of senescence during adulthood. The
results of this investigation provide an integrated picture of early-late life
trade-offs, underscoring the importance of accounting for environmental
conditions because of their potentially strong implications for population
dynamics.
PMID- 28514625
TI - "Latitudinal Gradients in Species Diversity": Reflections on Pianka's 1966
Article and a Look Forward.
PMID- 28514628
TI - A Modest Proposal for Unifying Macroevolution and Ecosystem Ecology.
PMID- 28514627
TI - What Kind of Maternal Effects Can Be Selected For in Fluctuating Environments?
AB - Just as phenotypic plasticity can evolve when developing individuals get
informational cues about their future adult environment, deterministic maternal
effects, where offspring trait values depend on the maternal environment, can
evolve when mothers gain reliable information about the environments their
offspring will face. Randomizing maternal effects (a type of diversifying bet
hedging), where offspring trait values are randomized, can evolve by natural
selection even when information about future environments is unavailable. We
investigate selection on both randomizing and deterministic maternal effects in
environments that show correlated fluctuations between two environmental states.
We compare the strength of selection for deterministic and randomizing maternal
effects and explicitly consider maternal fitness costs of producing offspring
with different phenotypes. Only a small set of environmental parameters allow
randomizing maternal effects to outcompete deterministic maternal effects; not
only must there be little or no information available about future environments,
but the frequency of each environment must fall within a narrow range. By
contrast, deterministic maternal effects can always invade an ancestral state
lacking a maternal effect even if the amount of environmental information
available is low. The long-term outcome may involve offspring trait value
randomization but only if trait values first evolve to cause extreme differences
in environment-specific fitness. Overall, deterministic maternal effects are more
likely to evolve by natural selection than randomizing maternal effects.
PMID- 28514629
TI - The Emergent Properties of Conspecific Attraction Can Limit a Species' Ability to
Track Environmental Change.
AB - Multiple biotic, abiotic, and evolutionary constraints interact to determine a
species' range. However, most species are not present in all suitable and
accessible locations. Dispersal ability may explain why many species do not
occupy all suitable habitat, but highly mobile species also exhibit a mismatch.
Habitat selection behavior where individuals are site faithful and settle near
conspecifics could create a social pressure that make a species' geographic range
resistant to change. We investigated this possibility by using an individual
based model of habitat selection where habitat quality moved each year. Our model
demonstrated the benefits of conspecific attraction in relatively stable
environments and its detrimental influence when habitat quality shifted rapidly.
These results were most apparent when adult survival was high, because site
fidelity led to more individuals occupying poor-quality habitat areas as habitat
quality changed. These individuals attracted other dispersing individuals,
thereby decreasing the ability to track shifts in habitat quality, which we refer
to as "social inertia." Consequently, social inertia may arise for species that
exhibit site fidelity and conspecific attraction, which may have conservation
implications in light of climate change and widespread alteration of natural
habitats.
PMID- 28514630
TI - Speciation and the Latitudinal Diversity Gradient: Insights from the Global
Distribution of Endemic Fish.
AB - The nearly universal pattern that species richness increases from the poles to
the equator (the latitudinal diversity gradient [LDG]) has been of intense
interest since its discovery by early natural-history explorers. Among the many
hypotheses proposed to explain the LDG, latitudinal variation in (1)
productivity, (2) time and area available for diversification, and (3) speciation
and/or extinction rates have recently received the most attention. Because
tropical regions are older and were formerly more widespread, these factors are
often intertwined, hampering efforts to distinguish their relative contributions
to the LDG. Here we examine the global distribution of endemic lake fishes to
determine how lake age, area, and latitude each affect the probability of
speciation and the extent of diversification occurring within a lake. We analyzed
the distribution of endemic fishes worldwide (1,933 species and subspecies from
47 families in 2,746 lakes) and find that the probability of a lake containing an
endemic species and the total number of endemics per lake increase with lake age
and area and decrease with latitude. Moreover, the geographic locations of
endemics in 34 of 41 families are found at lower latitudes than those of
nonendemics. We propose that the greater diversification of fish at low latitudes
may be driven in part by ecological opportunities promoted by tropical climates
and by the coevolution of species interactions.
PMID- 28514631
TI - The Hawk-Eyed Songbird: Retinal Morphology, Eye Shape, and Visual Fields of an
Aerial Insectivore.
AB - Swallows are a unique group of songbirds because they are active-pursuit
predators that execute all aspects of hunting prey in flight: search, detection,
pursuit, and capture. We show that swallows have evolved a visual system that is
unlike that of any other studied songbird. Swallows have a bifoveate retina that
provides sharp lateral and frontal vision, an unusually long eye that enhances
spatial resolution, a large posterior blind area, and a narrow binocular field.
We also show that swallows and diurnal raptors (hawks and falcons) have converged
on a similar visual configuration but that, interestingly, predatory songbirds
that ambush prey (flycatchers) have not converged on the same suite of traits.
Despite the commonly held belief that predators rely on binocular vision, the
temporal (frontally projecting) fovea present in swallows-but not present in
other songbirds-is likely not involved in binocular vision. Instead, swallows
have four nonoverlapping foveae in a 100 degrees arc around the beak, which can
improve the tracking of frontally located aerial prey that are engaging in
evasive maneuvers. Overall, vision in pursuit predators reflects the complex
sensory demands of hunting in the air at high speeds and emphasizes the
importance of acute frontal vision in predators.
PMID- 28514632
TI - A Waterborne Pursuit-Deterrent Signal Deployed by a Sea Urchin.
AB - Selection by consumers has led to the evolution of a vast array of defenses in
animals and plants. These defenses include physical structures, behaviors, and
chemical signals that mediate interactions with predators. Some of the strangest
defensive structures in nature are the globiferous pedicellariae of the
echinoderms. These are small venomous appendages with jaws and teeth that cover
the test of many sea urchins and sea stars. In this study, we report a unique use
of these defensive structures by the collector sea urchin Tripneustes gratilla.
In both the laboratory and the field, globiferous pedicellariae were unpalatable
to fish consumers. When subject to simulated predator attack, sea urchins
released a cloud of pedicellaria heads into the water column. Flume experiments
established the presence of a waterborne cue associated with this release of
pedicellariae that is deterrent to predatory fish. These novel results add to our
understanding of how the ecosystem-shaping sea urchin T. gratilla is able to
reach high densities in many reef habitats, with subsequent impacts on algal
cover.
PMID- 28514633
TI - Why Have Multiple Plastic Responses? Interactions between Color Change and Heat
Avoidance Behavior in Battus philenor Larvae.
AB - Having multiple plastic responses to a change in the environment, such as
increased temperature, can be adaptive for two major reasons: synergy (the
plastic responses perform better when expressed simultaneously) or
complementarity (each plastic response provides a greater net benefit in a
different environmental context). We investigated these hypotheses for two forms
of temperature-induced plasticity of Battus philenor caterpillars in southern
Arizona populations: color change (from black to red at high temperatures) and
heat avoidance behavior (movement from host to elevated refuges at high host
temperatures). Field assays using aluminum models showed that the cooling effect
of the red color is greatly reduced in a refuge position relative to that on a
host. Field assays with live caterpillars demonstrated that refuge seeking is
much more important for survival under hot conditions than coloration; however,
in those assays, red coloration reduced the need to seek refuges. Our results
support the complementarity hypothesis: refuge seeking facilitates survival
during daily temperature peaks, while color change reduces the need to leave the
host over longer warm periods. We propose that combinations of rapid but costly
short-term behavioral responses and slow but efficient long-term morphological
responses may be common when coping with temperature change.
PMID- 28514634
TI - Convergent Reversion to Single Mating in a Wasp Social Parasite.
AB - While eusociality arose in species with single-mating females, multiple mating by
queens has evolved repeatedly across the social ants, bees, and wasps.
Understanding the benefits and costs of multiple mating of queens is important
because polyandry results in reduced relatedness between siblings, reducing kin
selected benefits of helping while also selecting for secondary social traits
that reduce intracolony conflict. The leading hypothesis for the benefits of
polyandry in social insects emphasizes advantages of a genetically diverse
workforce. Workerless social parasite species (inquilines) provide a unique
opportunity to test this hypothesis, since they are derived from social ancestors
but do not produce workers of their own. Such parasites are thus predicted to
evolve single mating because they would experience the costs of multiple mating
but not the benefits if such benefits accrue through the production of a
genetically diverse group of workers. Here we show that the workerless social
parasite Dolichovespula arctica, a derived parasite of wasps, has reverted to
obligate single mating from a facultatively polyandrous ancestor, mirroring a
similar reversion from obligate polyandry to approximate monandry in a social
parasite of fungus-farming ants. This finding and a comparison with two other
cases where inquilinism did not induce reversal to monandry support the
hypothesis that facultative polyandry can be costly and may be maintained by
benefits of a genetically diverse workforce.
PMID- 28514635
TI - Specialization to Extremely Low-Nutrient Soils Limits the Nutritional
Adaptability of Plant Lineages.
AB - Specialization to extreme selective situations promotes the acquisition of traits
whose coadaptive integration may compromise evolutionary flexibility and
adaptability. We test this idea in the context of the foliar stoichiometry of
plants native to the South African Cape. Whereas foliar concentrations of
nitrogen, phosphorus (P), potassium (K), calcium, magnesium, and sodium showed
strong phylogenetic signal, as did the foliar ratios of these nutrients to P, the
same was not true of the corresponding soil values. In addition, although foliar
traits were often related to soil values, the coefficients of determination were
consistently low. These results identify foliar stoichiometry as having a strong
genetic component, with variation in foliar nutrient concentrations, especially
[P] and [K], being identified as potentially adaptive. Comparison of
stoichiometric variation across 11 similarly aged clades revealed consistently
low foliar nutrient concentrations in lineages showing specialization to
extremely low-nutrient fynbos heathlands. These lineages also display lower rates
of evolution of these traits as well as a reduced tendency for foliar [P] to
track soil [P]. Reduced evolutionary lability and adaptability in the nutritional
traits of fynbos-specialist lineages may explain the floristic distinctness of
the fynbos flora and implies a reduced scope for edaphically driven ecological
speciation.
PMID- 28514637
TI - Re-examining the Causes and Meaning of the Risk Allocation Hypothesis.
AB - The risk allocation hypothesis has inspired numerous studies seeking to
understand how temporal variation in predation risk affects prey foraging
behavior, but there has been debate about its generality and causes. I examined
how imperfect information affects its predictions and sought to clarify the
causes of the predicted patterns. I first confirmed that my modeling approach
given a threshold or linear fitness function-produced the risk allocation
prediction that prey increase their foraging efforts during low and high risk as
the proportion of high-risk periods increases. However, the causes of this result
and its robustness differed for the two fitness functions. When prey that had
evolved to use perfect information received imperfect information, risk
allocation was reduced. However, prey that evolved to use imperfect information
in some cases reversed the risk allocation prediction. The model also showed that
risk allocation occurs even when prey have no knowledge that the proportions of
low- and high-risk periods have changed. I conclude that risk allocation is
largely not driven by prey expectations about future states of the environment
but rather by the prey's current energetic state and time remaining. I discuss
the consequences for experimental design and explanations for empirical results.
PMID- 28514636
TI - Eco-Evolutionary Theory and Insect Outbreaks.
AB - Eco-evolutionary theory argues that population cycles in consumer-resource
interactions are partly driven by natural selection, such that changes in
densities and changes in trait values are mutually reinforcing. Evidence that the
theory explains cycles in nature, however, is almost nonexistent. Experimental
tests of model assumptions are logistically impractical for most organisms, while
for others, evidence that population cycles occur in nature is lacking. For
insect baculoviruses in contrast, tests of model assumptions are straightforward,
and there is strong evidence that baculoviruses help drive population cycles in
many insects, including the gypsy moth that we study here. We therefore used
field experiments with the gypsy moth baculovirus to test two key assumptions of
eco-evolutionary models of host-pathogen population cycles: that reduced host
infection risk is heritable and that it is costly. Our experiments confirm both
assumptions, and inserting parameters estimated from our data into eco
evolutionary insect-outbreak models gives cycles closely resembling gypsy moth
outbreak cycles in North America, whereas standard models predict unrealistic
stable equilibria. Our work shows that eco-evolutionary models are useful for
explaining outbreaks of forest insect defoliators, while widespread observations
of intense selection on defoliators in nature and of heritable and costly
resistance in defoliators in the lab together suggest that eco-evolutionary
dynamics may play a general role in defoliator outbreaks.
PMID- 28514639
TI - Warming-Induced Changes to Body Size Stabilize Consumer-Resource Dynamics.
AB - Both body size and temperature directly influence consumer-resource dynamics.
There is also widespread empirical evidence for the temperature-size rule (TSR),
which creates a negative relationship between temperature and body size. However,
it is not known how the TSR affects community dynamics. Here we integrate
temperature- and size-dependent models to include indirect effects of warming,
through changes in body size, to answer the question, How does the TSR affect the
predicted response of consumer-resource systems to warming? We find that the TSR
is expected to maintain consumer-resource biomass ratios and buffer the community
from extinctions under warming. While our results are limited to conditions where
organisms are below their thermal optimum, they hold under a range of realistic
temperature-size responses and are robust to the type of functional response. Our
analyses suggest that the widely observed TSR may reduce the impacts of warming
on consumer-resource systems.
PMID- 28514638
TI - The Evolution of Cooperation: Interacting Phenotypes among Social Partners.
AB - Models of cooperation among nonkin suggest that social assortment is important
for the evolution of cooperation. Theory predicts that interacting phenotypes,
whereby an individual's behavior depends on the behavior of its social partners,
can drive such social assortment. We measured repeated indirect genetic effects
(IGEs) during cooperative predator inspection in eight populations of Trinidadian
guppies (Poecilia reticulata) that vary in their evolutionary history of
predation. Four broad patterns emerged that were dependent on river, predation
history, and sex: (i) current partner behavior had the largest effect on focal
behavior, with fish from low-predation habitats responding more to their social
partners than fish from high-predation habitats; (ii) different focal/partner
behavior combinations can generate cooperation; (iii) some high-predation fish
exhibited carryover effects across social partners; and (iv) high-predation fish
were more risk averse. These results provide the first large-scale comparison of
interacting phenotypes during cooperation across wild animal populations,
highlighting the potential importance of IGEs in maintaining cooperation.
Intriguingly, while focal fish responded strongly to current social partners,
carryover effects between social partners suggest generalized reciprocity (in
which one helps anyone if helped by someone) may contribute to the evolution of
cooperation in some, but not all, populations of guppies.
PMID- 28514640
TI - Digital disruption 'syndromes' in a hospital: important considerations for the
quality and safety of patient care during rapid digital transformation.
AB - The digital transformation of hospitals in Australia is occurring rapidly in
order to facilitate innovation and improve efficiency. Rapid transformation can
cause temporary disruption of hospital workflows and staff as processes are
adapted to the new digital workflows. The aim of this paper is to outline various
types of digital disruption and some strategies for effective management. A large
tertiary university hospital recently underwent a rapid, successful roll-out of
an integrated electronic medical record (EMR). We observed this transformation
and propose several digital disruption "syndromes" to assist with understanding
and management during digital transformation: digital deceleration, digital
transparency, digital hypervigilance, data discordance, digital churn and post
digital 'depression'. These 'syndromes' are defined and discussed in detail.
Successful management of this temporary digital disruption is important to ensure
a successful transition to a digital platform.
PMID- 28514641
TI - Mapping workforce configuration and operational models in Australian emergency
departments: a national survey.
AB - Objective Hospital emergency departments (ED) in Australia and internationally
have been experiencing increased demand, resulting in reduced hospital quality,
impaired access and adverse health outcomes. Effective evaluation of new ED
service models and their effect on outcomes is reliant on baseline measures of
the staffing configuration and organisational characteristics of the EDs being
studied. The aim of the present study was to comprehensively measure these
variables in Australian EDs. Methods Australian hospital EDs with 24-h medical
and nursing cover were identified and invited to participate in the study.
Telephone interviews were conducted with nursing or medical department managers
to collect data related to hospital characteristics, ED workforce and training
and ED service and operational models. Results Surveys were completed in 87% of
the population sample (n=135). Metropolitan EDs were significantly more likely to
retain higher full-time equivalents (FTEs) in several medical (staff specialist,
registrar, resident and intern) and nursing (nurse practitioner (NP), nurse
educator, nurse unit manager and registered nurse) positions. NPs were employed
by 52% of Australian EDs overall, but this ranged from 40% to 75% depending on
jurisdiction. The most commonly used operational models were FastTrack teams (72%
of EDs), short-stay/observational unit (59%) and patient liaison models for aged
care (84%) and mental health (61%). EDs that employed NPs were significantly more
likely to use FastTrack (P=0.002). Allied health services most frequently
available within these EDs were radiology (60%), social work (69%), physiotherapy
(70%) and pharmacy (65%). Conclusions The present study has established a
baseline measure of the staffing configuration and organisational characteristics
of Australian EDs. What is known about the topic? EDs are overcrowded due, in
part, to the combined effect of increased service demand and access block.
Innovative service and workforce models have been implemented by health
departments aiming to improve service and performance. National uptake of these
service and workforce innovations is unknown. What does this paper add? The
present study is the most comprehensive to date profiling Australian EDs covering
hospital characteristics, workforce configuration, operational models and NP
service patterns and practice. What are the implications for practitioners?
Information from the present study will assist health service planners to
evaluate workforce and service reform models, and to monitor trends in emergency
service development.
PMID- 28514642
TI - Congenital adrenal hyperplasia due to 11-hydroxylase deficiency-Compound
heterozygous mutations of a prevalent and two novel CYP11B1 mutations.
AB - 11beta-hydroxylase deficiency (11beta-OHD) occurs in about 5-8% of congenital
adrenal hyperplasia (CAH). In this study, we identified three CYP11B1 (encoding
Cytochrome P450 11B1) heterozygous mutations: c.1358G>C (p.R453Q), c.1229T>G
(p.L410R) and c.1231G>T (p.G411C) in a Chinese CAH patient due to classic 11beta
OHD. His parents were healthy and respectively carried the prevalent mutation
c.1358G>C (p.R453Q), and the two novel mutations c.1229T>G (p.L410R) and
c.1231G>T (p.G411C). In vitro expression studies, immunofluorescence demonstrated
that wild type and mutant (L410R and G411C) proteins of CYP11B1 were correctly
expressed on the mitochondria, and enzyme activity assay revealed the mutant
reduced the 11-hydroxylase activity to 10% (P<0.001) for the conversion of 11beta
deoxycortisol to cortisol. Subsequently, three dimensional homology models for
the normal and mutant proteins were built by using the x-ray structure of the
human CYP11B2 as a template. Interestingly, in the heme binding site I helix, a
change from helix to loop in four amino acide took place in the mutant model. In
conclusion, this study expands the spectrum of mutations in CYP11B1 causing to
11beta-OHD and provides evidence for prenatal diagnosis and genetic counseling.
In addition, our results confirm the two novel CYP11B1 mutations led to impaired
11-hydroxylase activity in vitro.
PMID- 28514644
TI - The importance of hormonal circadian rhythms in daily feeding patterns: An
illustration with simulated pigs.
AB - The interaction between hormonal circadian rhythms and feeding behaviour is not
well understood. This study aimed to deepen our understanding of mechanisms
underlying circadian feeding behaviour in animals, using pigs, Sus scrofa, as a
case study. Pigs show an alternans feeding pattern, that is, a small peak of feed
intake at the beginning of the day and a larger peak at the end of the day. We
simulated the feeding behaviour of pigs over a 24h period. The simulation model
contained mechanisms that regulate feeding behaviour of animals, including:
processing of feed in the gastrointestinal tract, fluctuation in energy balance,
circadian rhythms of melatonin and cortisol and motivational decision-making.
From the interactions between these various processes, feeding patterns (e.g.
feed intake, meal frequency, feeding rate) emerge. These feeding patterns, as
well as patterns for the underlying mechanisms (e.g. energy expenditure), fitted
empirical data well, indicating that our model contains relevant mechanisms. The
circadian rhythms of cortisol and melatonin explained the alternans pattern of
feeding in pigs. Additionally, the timing and amplitude of cortisol peaks
affected the diurnal and nocturnal peaks in feed intake. Furthermore, our results
suggest that circadian rhythms of other hormones, such as leptin and ghrelin, are
less important in circadian regulation of feeding behaviour than previously
thought. These results are relevant to animal species with a metabolic and
endocrine system similar to that of pigs, such as humans. Moreover, the modelling
approach to understand feeding behaviour can be applied to other animal species.
PMID- 28514645
TI - Oleanolic acid modulates the renin-angiotensin system and cardiac natriuretic
hormone concomitantly with volume and pressure balance in rats.
AB - Oleanolic acid is known to possess beneficial effects on the regulation of the
cardiovascular homeostasis. However, the exact nature of the role of oleanolic
acid on the regulation of body fluid balance and blood pressure homeostasis and
its mechanisms involved are not well defined. Experiments were performed to
identify the effects of oleanolic acid on the renin-angiotensin system and
cardiac natriuretic hormone (ANP) system, and also renal function and blood
pressure in normotensive and renovascular hypertensive rats. The change in the
plasma levels of hormones and the expressions of renin, angiotensin II receptors,
ANP, natriuretic peptide receptor-C, M2 muscarinic receptor and GIRK4 were
determined in the kidney, heart and aorta. Oleanolic acid was administered orally
for 1 or 3 weeks. Here, we found that oleanolic acid suppressed plasma levels of
renin activity and aldosterone and intrarenal levels of renin and angiotensin II
type 1 receptor expression and increased angiotensin II type 2 receptor in
normotensive and hypertensive rats. Also, oleanolic acid increased plasma levels
of ANP. Further, oleanolic acid suppressed angiotensin II type 1 receptor and
natriuretic peptide receptor-C expression and increased angiotensin II type 2
receptor and ANP expression in the heart and aorta. Along with these changes,
oleanolic acid accentuated urinary volume, electrolyte excretion and glomerular
filtration rate in normotensive rats and suppressed arterial blood pressure in
hypertensive rats. These findings suggest that beneficial effects of oleanolic
acid on the cardiorenal system are closely associated with its roles on the renin
angiotensin system and cardiac natriuretic hormone system.
PMID- 28514643
TI - Yorkie regulates epidermal wound healing in Drosophila larvae independently of
cell proliferation and apoptosis.
AB - Yorkie (Yki), the transcriptional co-activator of the Hippo signaling pathway,
has well-characterized roles in balancing apoptosis and cell division during
organ growth control. Yki is also required in diverse tissue regenerative
contexts. In most cases this requirement reflects its well-characterized roles in
balancing apoptosis and cell division. Whether Yki has repair functions outside
of the control of cell proliferation, death, and growth is not clear. Here we
show that Yki and Scalloped (Sd) are required for epidermal wound closure in the
Drosophila larval epidermis. Using a GFP-tagged Yki transgene we show that Yki
transiently translocates to some epidermal nuclei upon wounding. Genetic analysis
strongly suggests that Yki interacts with the known wound healing pathway, Jun N
terminal kinase (JNK), but not with Platelet Derived Growth Factor/Vascular
Endothelial Growth Factor receptor (Pvr). Yki likely acts downstream of or
parallel to JNK signaling and does not appear to regulate either proliferation or
apoptosis in the larval epidermis during wound repair. Analysis of actin
structures after wounding suggests that Yki and Sd promote wound closure through
actin regulation. In sum, we found that Yki regulates an epithelial tissue repair
process independently of its previously documented roles in balancing
proliferation and apoptosis.
PMID- 28514647
TI - The importance of bioinformatics for connecting data-driven lipidomics and
biological insights.
PMID- 28514648
TI - Determination of fenobucarb residues in animal and aquatic food products using
liquid chromatography-tandem mass spectrometry coupled with a QuEChERS extraction
method.
AB - A modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction
method coupled with liquid chromatography-electrospray ionization tandem mass
spectrometry (LC-ESI+/MS-MS) was developed for quantification of fenobucarb
residues in animal food products, such as porcine muscle, egg, and whole milk,
and aquatic food products, such as eel, flatfish, and shrimp. Acetonitrile with
the addition of 0.1% trifluoroacetic acid was employed as an extraction solvent
and was compared with acetonitrile alone and 0.1% formic acid in acetonitrile.
All extracted samples were purified using C18 sorbent. The best extraction
efficiencies, expressed as recovery at two spiking levels equivalent to 1- and 2
times the limit of quantification (LOQ=2MUg/kg) were achieved using 0.1%
trifluoroacetic acid in acetonitrile and ranged from 61.38 to 102.21% in all
matrices, with relative standard deviations (RSDs) < 13% (except for the low
spiking of porcine muscle and the high spiking of whole milk, for which the RSDs
were>20%). Six-point matrix-matched calibration was used for quantification and
the determination coefficients were good (R2>=0.9865). The method was verified by
application to samples purchased from local markets and none of the samples
tested positive. In conclusion, the developed method is simple and versatile and
can be used for the routine detection of fenobucarb in different animal food
products having varying protein and fat contents with satisfactory accuracy and
precision.
PMID- 28514646
TI - Heparin removal by ecteola-cellulose pre-treatment enables the use of plasma
samples for accurate measurement of anti-Yellow fever virus neutralizing
antibodies.
AB - Technological innovations in vaccinology have recently contributed to bring about
novel insights for the vaccine-induced immune response. While the current
protocols that use peripheral blood samples may provide abundant data, a range of
distinct components of whole blood samples are required and the different
anticoagulant systems employed may impair some properties of the biological
sample and interfere with functional assays. Although the interference of heparin
in functional assays for viral neutralizing antibodies such as the functional
plaque-reduction neutralization test (PRNT), considered the gold-standard method
to assess and monitor the protective immunity induced by the Yellow fever virus
(YFV) vaccine, has been well characterized, the development of pre-analytical
treatments is still required for the establishment of optimized protocols. The
present study intended to optimize and evaluate the performance of pre-analytical
treatment of heparin-collected blood samples with ecteola-cellulose (ECT) to
provide accurate measurement of anti-YFV neutralizing antibodies, by PRNT. The
study was designed in three steps, including: I. Problem statement; II. Pre
analytical steps; III. Analytical steps. Data confirmed the interference of
heparin on PRNT reactivity in a dose-responsive fashion. Distinct sets of
conditions for ECT pre-treatment were tested to optimize the heparin removal. The
optimized protocol was pre-validated to determine the effectiveness of heparin
plasma:ECT treatment to restore the PRNT titers as compared to serum samples. The
validation and comparative performance was carried out by using a large range of
serum vs heparin plasma:ECT 1:2 paired samples obtained from unvaccinated and
17DD-YFV primary vaccinated subjects. Altogether, the findings support the use of
heparin plasma:ECT samples for accurate measurement of anti-YFV neutralizing
antibodies.
PMID- 28514624
TI - Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease.
AB - BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib
substantially raises the high-density lipoprotein (HDL) cholesterol level,
reduces the low-density lipoprotein (LDL) cholesterol level, and enhances
cellular cholesterol efflux capacity. We sought to determine the effect of
evacetrapib on major adverse cardiovascular outcomes in patients with high-risk
vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo
controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the
following conditions: an acute coronary syndrome within the previous 30 to 365
days, cerebrovascular atherosclerotic disease, peripheral vascular arterial
disease, or diabetes mellitus with coronary artery disease. Patients were
randomly assigned to receive either evacetrapib at a dose of 130 mg or matching
placebo, administered daily, in addition to standard medical therapy. The primary
efficacy end point was the first occurrence of any component of the composite of
death from cardiovascular causes, myocardial infarction, stroke, coronary
revascularization, or hospitalization for unstable angina. RESULTS: At 3 months,
a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib
versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL
cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo.
After 1363 of the planned 1670 primary end-point events had occurred, the data
and safety monitoring board recommended that the trial be terminated early
because of a lack of efficacy. After a median of 26 months of evacetrapib or
placebo, a primary end-point event occurred in 12.9% of the patients in the
evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01;
95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the
cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on
established lipid biomarkers, treatment with evacetrapib did not result in a
lower rate of cardiovascular events than placebo among patients with high-risk
vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number,
NCT01687998 .).
PMID- 28514649
TI - Widespread Mitotic Bookmarking by Histone Marks and Transcription Factors in
Pluripotent Stem Cells.
AB - During mitosis, transcription is halted and many chromatin features are lost,
posing a challenge for the continuity of cell identity, particularly in fast
cycling stem cells, which constantly balance self-renewal with differentiation.
Here we show that, in pluripotent stem cells, certain histone marks and stem cell
regulators remain associated with specific genomic regions of mitotic chromatin,
a phenomenon known as mitotic bookmarking. Enhancers of stem cell-related genes
are bookmarked by both H3K27ac and the master regulators OCT4, SOX2, and KLF4,
while promoters of housekeeping genes retain high levels of mitotic H3K27ac in a
cell-type invariant manner. Temporal degradation of OCT4 during mitotic exit
compromises its ability both to maintain and induce pluripotency, suggesting that
its regulatory function partly depends on its bookmarking activity. Together, our
data document a widespread yet specific bookmarking by histone modifications and
transcription factors promoting faithful and efficient propagation of stemness
after cell division.
PMID- 28514650
TI - The INO80 Complex Removes H2A.Z to Promote Presynaptic Filament Formation during
Homologous Recombination.
AB - The INO80 complex (INO80-C) is an evolutionarily conserved nucleosome remodeler
that acts in transcription, replication, and genome stability. It is required for
resistance against genotoxic agents and is involved in the repair of DNA double
strand breaks (DSBs) by homologous recombination (HR). However, the causes of the
HR defect in INO80-C mutant cells are controversial. Here, we unite previous
findings using a system to study HR with high spatial resolution in budding
yeast. We find that INO80-C has at least two distinct functions during HR-DNA end
resection and presynaptic filament formation. Importantly, the second function is
linked to the histone variant H2A.Z. In the absence of H2A.Z, presynaptic
filament formation and HR are restored in INO80-C-deficient mutants, suggesting
that presynaptic filament formation is the crucial INO80-C function during HR.
PMID- 28514651
TI - Modeling Genomic Instability and Selection Pressure in a Mouse Model of Melanoma.
AB - Tumor evolution is an iterative process of selection for pro-oncogenic
aberrations. This process can be accelerated by genomic instability, but how it
interacts with different selection bottlenecks to shape the evolving genomic
landscape remains understudied. Here, we assessed tumor initiation and therapy
resistance bottlenecks in mouse models of melanoma, with or without genomic
instability. At the initiation bottleneck, whole-exome sequencing revealed that
drug-naive tumors were genomically silent, and this was surprisingly unaffected
when genomic instability was introduced via telomerase inactivation. We
hypothesize that the strong engineered alleles created low selection pressure. At
the therapy resistance bottleneck, strong selective pressure was applied using a
BRAF inhibitor. In the absence of genomic instability, tumors acquired a non
genomic drug resistance mechanism. By contrast, telomerase-deficient, drug
resistant melanomas acquired highly recurrent copy number gains. These proof-of
principle experiments demonstrate how different selection pressures can interact
with genomic instability to impact tumor evolution.
PMID- 28514654
TI - Crystal Structure of Tetrameric Arabidopsis MYC2 Reveals the Mechanism of
Enhanced Interaction with DNA.
AB - Jasmonates (JAs) are essential plant hormones that play important roles in the
regulation of plant growth and the response to environmental stress. In the JA
signaling pathway, the core transcription factors are a class of basic helix-loop
helix (bHLH) proteins, including MYC2, MYC3, and MYC4, that have different
regulatory capacities. Here, we report the 2.7 A crystal structure of the MYC2
bHLH domain complexed with G-box DNA, showing a cis-tetrameric structure.
Biochemical assays confirmed that full-length MYC2 forms a stable homo-tetramer
both in solution and in DNA-bound states, whereas MYC3 forms only a homodimer.
Isothermal titration calorimetry (ITC) assays demonstrated that tetramerization
enhanced DNA binding affinity, and fluorescence resonance energy transfer (FRET)
assay indicated DNA looping potential of tetrameric MYC2. Luciferase assay
further confirmed the importance of tetramerization in transcriptional
regulation. Our studies provide a mechanistic explanation for the regulatory
differences of MYC transcription factors.
PMID- 28514652
TI - Thymidine Catabolism as a Metabolic Strategy for Cancer Survival.
AB - Thymidine phosphorylase (TP), a rate-limiting enzyme in thymidine catabolism,
plays a pivotal role in tumor progression; however, the mechanisms underlying
this role are not fully understood. Here, we found that TP-mediated thymidine
catabolism could supply the carbon source in the glycolytic pathway and thus
contribute to cell survival under conditions of nutrient deprivation. In TP
expressing cells, thymidine was converted to metabolites, including glucose 6
phosphate, lactate, 5-phospho-alpha-D-ribose 1-diphosphate, and serine, via the
glycolytic pathway both in vitro and in vivo. These thymidine-derived metabolites
were required for the survival of cells under low-glucose conditions.
Furthermore, activation of thymidine catabolism was observed in human gastric
cancer. These findings demonstrate that thymidine can serve as a glycolytic
pathway substrate in human cancer cells.
PMID- 28514653
TI - The Presence of Interleukin-13 at Pancreatic ADM/PanIN Lesions Alters Macrophage
Populations and Mediates Pancreatic Tumorigenesis.
AB - The contributions of the innate immune system to the development of pancreatic
cancer are still ill defined. Inflammatory macrophages can initiate metaplasia of
pancreatic acinar cells to a duct-like phenotype (acinar-to-ductal metaplasia
[ADM]), which then gives rise to pancreatic intraepithelial neoplasia (PanIN)
when oncogenic KRas is present. However, it remains unclear when and how this
inflammatory macrophage population is replaced by tumor-promoting macrophages.
Here, we demonstrate the presence of interleukin-13 (IL-13), which can convert
inflammatory into Ym1+ alternatively activated macrophages, at ADM/PanIN lesions.
We further show that Ym1+ macrophages release factors, such as IL-1ra and CCL2,
to drive pancreatic fibrogenesis and tumorigenesis. Treatment of mice expressing
oncogenic KRas under an acinar cell-specific promoter with a neutralizing
antibody for IL-13 significantly decreased the accumulation of alternatively
activated macrophages at these lesions, resulting in decreased fibrosis and
lesion growth.
PMID- 28514655
TI - Inhibitory Control of Feature Selectivity in an Object Motion Sensitive Circuit
of the Retina.
AB - Object motion sensitive (OMS) W3-retinal ganglion cells (W3-RGCs) in mice respond
to local movements in a visual scene but remain silent during self-generated
global image motion. The excitatory inputs that drive responses of W3-RGCs to
local motion were recently characterized, but which inhibitory neurons suppress
W3-RGCs' responses to global motion, how these neurons encode motion information,
and how their connections are organized along the excitatory circuit axis remains
unknown. Here, we find that a genetically identified amacrine cell (AC) type, TH2
AC, exhibits fast responses to global motion and slow responses to local motion.
Optogenetic stimulation shows that TH2-ACs provide strong GABAA receptor-mediated
input to W3-RGCs but only weak input to upstream excitatory neurons. Cell-type
specific silencing reveals that temporally coded inhibition from TH2-ACs cancels
W3-RGC spike responses to global but not local motion stimuli and, thus, controls
the feature selectivity of OMS signals sent to the brain.
PMID- 28514656
TI - Endogenous Replication Stress in Mother Cells Leads to Quiescence of Daughter
Cells.
AB - Mammalian cells have two fundamentally different states, proliferative and
quiescent, but our understanding of how and why cells switch between these states
is limited. We previously showed that actively proliferating populations contain
a subpopulation that enters quiescence (G0) in an apparently stochastic manner.
Using single-cell time-lapse imaging of CDK2 activity and DNA damage, we now show
that unresolved endogenous replication stress in the previous (mother) cell cycle
prompts p21-dependent entry of daughter cells into quiescence immediately after
mitosis. Furthermore, the amount of time daughter cells spend in quiescence is
correlated with the extent of inherited damage. Our study thus links replication
errors in one cell cycle to the fate of daughter cells in the subsequent cell
cycle. More broadly, this work reveals that entry into quiescence is not purely
stochastic but has a strong deterministic component arising from a memory of
events that occurred in the previous generation(s).
PMID- 28514658
TI - CNS Macrophages Control Neurovascular Development via CD95L.
AB - The development of neurons and vessels shares striking anatomical and molecular
features, and it is presumably orchestrated by an overlapping repertoire of
extracellular signals. CNS macrophages have been implicated in various
developmental functions, including the morphogenesis of neurons and vessels.
However, whether CNS macrophages can coordinately influence neurovascular
development and the identity of the signals involved therein is unclear. Here, we
demonstrate that activity of the cell surface receptor CD95 regulates neuronal
and vascular morphogenesis in the post-natal brain and retina. Furthermore, we
identify CNS macrophages as the main source of CD95L, and macrophage-specific
deletion thereof reduces both neurovascular complexity and synaptic activity in
the brain. CD95L-induced neuronal and vascular growth is mediated through src
family kinase (SFK) and PI3K signaling. Together, our study highlights a
coordinated neurovascular development instructed by CNS macrophage-derived CD95L,
and it underlines the importance of macrophages for the establishment of the
neurovascular network during CNS development.
PMID- 28514657
TI - Huntington's Disease iPSC-Derived Brain Microvascular Endothelial Cells Reveal
WNT-Mediated Angiogenic and Blood-Brain Barrier Deficits.
AB - Brain microvascular endothelial cells (BMECs) are an essential component of the
blood-brain barrier (BBB) that shields the brain against toxins and immune cells.
While BBB dysfunction exists in neurological disorders, including Huntington's
disease (HD), it is not known if BMECs themselves are functionally compromised to
promote BBB dysfunction. Further, the underlying mechanisms of BBB dysfunction
remain elusive given limitations with mouse models and post-mortem tissue to
identify primary deficits. We undertook a transcriptome and functional analysis
of human induced pluripotent stem cell (iPSC)-derived BMECs (iBMEC) from HD
patients or unaffected controls. We demonstrate that HD iBMECs have intrinsic
abnormalities in angiogenesis and barrier properties, as well as in signaling
pathways governing these processes. Thus, our findings provide an iPSC-derived
BBB model for a neurodegenerative disease and demonstrate autonomous
neurovascular deficits that may underlie HD pathology with implications for
therapeutics and drug delivery.
PMID- 28514661
TI - Innate Recognition of Intracellular Bacterial Growth Is Driven by the TIFA
Dependent Cytosolic Surveillance Pathway.
AB - Intestinal epithelial cells (IECs) act as sentinels for incoming pathogens.
Cytosol-invasive bacteria, such as Shigella flexneri, trigger a robust pro
inflammatory nuclear factor kappaB (NF-kappaB) response from IECs that is
believed to depend entirely on the peptidoglycan sensor NOD1. We found that,
during Shigella infection, the TRAF-interacting forkhead-associated protein A
(TIFA)-dependent cytosolic surveillance pathway, which senses the bacterial
metabolite heptose-1,7-bisphosphate (HBP), functions after NOD1 to detect
bacteria replicating free in the host cytosol. Whereas NOD1 mediated a transient
burst of NF-kappaB activation during bacterial entry, TIFA sensed HBP released
during bacterial replication, assembling into large signaling complexes to drive
a dynamic inflammatory response that reflected the rate of intracellular
bacterial proliferation. Strikingly, IECs lacking TIFA were unable to
discriminate between proliferating and stagnant intracellular bacteria, despite
the NOD1/2 pathways being intact. Our results define TIFA as a rheostat for
intracellular bacterial replication, escalating the immune response to invasive
Gram-negative bacteria that exploit the host cytosol for growth.
PMID- 28514659
TI - The Intergenic Recombinant HLA-B*46:01 Has a Distinctive Peptidome that Includes
KIR2DL3 Ligands.
AB - HLA-B*46:01 was formed by an intergenic mini-conversion, between HLA-B*15:01 and
HLA-C*01:02, in Southeast Asia during the last 50,000 years, and it has since
become the most common HLA-B allele in the region. A functional effect of the
mini-conversion was introduction of the C1 epitope into HLA-B*46:01, making it an
exceptional HLA-B allotype that is recognized by the C1-specific natural killer
(NK) cell receptor KIR2DL3. High-resolution mass spectrometry showed that HLA
B*46:01 has a low-diversity peptidome that is distinct from those of its parents.
A minority (21%) of HLA-B*46:01 peptides, with common C-terminal characteristics,
form ligands for KIR2DL3. The HLA-B*46:01 peptidome is predicted to be enriched
for peptide antigens derived from Mycobacterium leprae. Overall, the results
indicate that the distinctive peptidome and functions of HLA-B*46:01 provide
carriers with resistance to leprosy, which drove its rapid rise in frequency in
Southeast Asia.
PMID- 28514660
TI - Absence of Specific Chlamydia trachomatis Inclusion Membrane Proteins Triggers
Premature Inclusion Membrane Lysis and Host Cell Death.
AB - Chlamydia trachomatis is a human pathogen associated with significant morbidity
worldwide. As obligate intracellular parasites, chlamydiae must survive within
eukaryotic cells for sufficient time to complete their developmental cycle. To
promote host cell survival, chlamydiae express poorly understood anti-apoptotic
factors. Using recently developed genetic tools, we show that three inclusion
membrane proteins (Incs) out of eleven examined are required for inclusion
membrane stability and avoidance of host cell death pathways. In the absence of
specific Incs, premature inclusion lysis results in recognition by
autophagolysosomes, activation of intrinsic apoptosis, and premature termination
of the chlamydial developmental cycle. Inhibition of autophagy or knockdown of
STING prevented host cell death and activation of intrinsic apoptosis.
Significantly, these findings emphasize the importance of Incs in the
establishment of a replicative compartment that sequesters the pathogen from host
surveillance systems.
PMID- 28514662
TI - A Murine Intestinal Intraepithelial NKp46-Negative Innate Lymphoid Cell
Population Characterized by Group 1 Properties.
AB - The Ly49E receptor is preferentially expressed on murine innate-like lymphocytes,
such as epidermal Vgamma3 T cells, intestinal intraepithelial CD8alphaalpha+ T
lymphocytes, and CD49a+ liver natural killer (NK) cells. As the latter have
recently been shown to be distinct from conventional NK cells and have innate
lymphoid cell type 1 (ILC1) properties, we investigated Ly49E expression on
intestinal ILC populations. Here, we show that Ly49E expression is very low on
known ILC populations, but it can be used to define a previously unrecognized
intraepithelial innate lymphoid population. This Ly49E-positive population is
negative for NKp46 and CD8alphaalpha, expresses CD49a and CD103, and requires T
bet expression and IL-15 signaling for differentiation and/or survival.
Transcriptome analysis reveals a group 1 ILC gene profile, different from NK
cells, iCD8alpha cells, and intraepithelial ILC1. Importantly, NKp46
CD8alphaalpha-Ly49E+ cells produce interferon (IFN)-gamma, suggesting that this
previously unrecognized population may contribute to Th1-mediated immunity.
PMID- 28514663
TI - Fatty Acid Oxidation in Zebrafish Adipose Tissue Is Promoted by 1alpha,25(OH)2D3.
AB - 1alpha,25(OH)2D3 (vitamin D3) is crucial for mineral homeostasis in mammals, but
the precise effects of 1alpha,25(OH)2D3 in adipose tissue remain to be clarified
in vivo. The initial 25-hydroxylation is catalyzed by liver microsomal cytochrome
P450 2R1 (CYP2R1), which is conserved in vertebrates. To probe the physiological
function(s) of 1alpha,25(OH)2D3 in teleosts, we generated two independent cyp2r1
deficient zebrafish lines. These mutants exhibit retarded growth and increased
obesity, especially in the visceral adipose tissue (VAT). These defects could be
rescued with 25(OH)D3 treatments. ChIP-PCR analyses demonstrated that pgc1a is
the target of the vitamin D receptor in the liver and VAT of zebrafish.
Significantly decreased protein levels of Pgc1a, impaired mitochondrial
biogenesis, and free fatty acid oxidation are also observed in the cyp2r1 mutant
VAT. Our results demonstrate that regulation of 1alpha,25(OH)2D3 during lipid
metabolism occurs through the regulation of Pgc1a for mitochondrial biogenesis
and oxidative metabolism within zebrafish VAT.
PMID- 28514665
TI - Systems Analysis Reveals High Genetic and Antigen-Driven Predetermination of
Antibody Repertoires throughout B Cell Development.
AB - Antibody repertoire diversity and plasticity is crucial for broad protective
immunity. Repertoires change in size and diversity across multiple B cell
developmental stages and in response to antigen exposure. However, we still lack
fundamental quantitative understanding of the extent to which repertoire
diversity is predetermined. Therefore, we implemented a systems immunology
framework for quantifying repertoire predetermination on three distinct levels:
(1) B cell development (pre-B cell, naive B cell, plasma cell), (2) antigen
exposure (three structurally different proteins), and (3) four antibody
repertoire components (V-gene usage, clonal expansion, clonal diversity,
repertoire size) extracted from antibody repertoire sequencing data (400 million
reads). Across all three levels, we detected a dynamic balance of high genetic
(e.g., >90% for V-gene usage and clonal expansion in naive B cells) and antigen
driven (e.g., 40% for clonal diversity in plasma cells) predetermination and
stochastic variation. Our study has implications for the prediction and
manipulation of humoral immunity.
PMID- 28514664
TI - Lack of MTTP Activity in Pluripotent Stem Cell-Derived Hepatocytes and
Cardiomyocytes Abolishes apoB Secretion and Increases Cell Stress.
AB - Abetalipoproteinemia (ABL) is an inherited disorder of lipoprotein metabolism
resulting from mutations in microsomal triglyceride transfer protein (MTTP). In
addition to expression in the liver and intestine, MTTP is expressed in
cardiomyocytes, and cardiomyopathy has been reported in several ABL cases. Using
induced pluripotent stem cells (iPSCs) generated from an ABL patient homozygous
for a missense mutation (MTTPR46G), we show that human hepatocytes and
cardiomyocytes exhibit defects associated with ABL disease, including loss of
apolipoprotein B (apoB) secretion and intracellular accumulation of lipids.
MTTPR46G iPSC-derived cardiomyocytes failed to secrete apoB, accumulated
intracellular lipids, and displayed increased cell death, suggesting intrinsic
defects in lipid metabolism due to loss of MTTP function. Importantly, these
phenotypes were reversed after the correction of the MTTPR46G mutation by
CRISPR/Cas9 gene editing. Together, these data reveal clear cellular defects in
iPSC-derived hepatocytes and cardiomyocytes lacking MTTP activity, including a
cardiomyocyte-specific regulated stress response to elevated lipids.
PMID- 28514667
TI - A Design Principle for an Autonomous Post-translational Pattern Formation.
PMID- 28514668
TI - Concurrent white matter bundles and grey matter networks using independent
component analysis.
AB - Developments in non-invasive diffusion MRI tractography techniques have permitted
the investigation of both the anatomy of white matter pathways connecting grey
matter regions and their structural integrity. In parallel, there has been an
expansion in automated techniques aimed at parcellating grey matter into distinct
regions based on functional imaging. Here we apply independent component analysis
to whole-brain tractography data to automatically extract brain networks based on
their associated white matter pathways. This method decomposes the tractography
data into components that consist of paired grey matter 'nodes' and white matter
'edges', and automatically separates major white matter bundles, including known
cortico-cortical and cortico-subcortical tracts. We show how this framework can
be used to investigate individual variations in brain networks (in terms of both
nodes and edges) as well as their associations with individual differences in
behaviour and anatomy. Finally, we investigate correspondences between
tractography-based brain components and several canonical resting-state networks
derived from functional MRI.
PMID- 28514669
TI - The relationship between cognition and depressive symptoms, and factors modifying
this association, in Alzheimer's disease: A multivariate multilevel model.
AB - OBJECTIVES: To examine whether there was a bidirectional association between
cognition and depressive symptoms in Alzheimer's disease (AD), and to explore the
role of socio-demographic factors and daily performance in this association.
METHODS: We conducted a longitudinal study of 104 community-dwelling patients
with confirmed AD from Taiyuan, China. We assessed cognition and depressive
symptoms (dependent variables) with the Montreal Cognitive Assessment (MoCA) and
the Geriatric Depression Scale-30 (GDS-30), respectively. Socio-demographic
information and daily performance were treated as explanatory variables. A
multivariate multilevel model was built to investigate the interrelationship
between patients' cognition and depression, as well as the effect of related
factors on both outcomes. RESULTS: MoCA scores were negatively correlated with
GDS-30 both at the subject level (correlation coefficient r3=-0.68, chi2=19.26,
P<0.001) and time point level (r2=-0.35, chi2=35.68, P<0.001) in patients with
AD. Multivariate analysis showed several significant factors for cognitive
function, including educational level, personality, hobbies, exercise, reading,
aluminum utensil use, dietary restriction and hypertension (regression
coefficients: 0.60, 0.52, 0.51, 0.48, 0.45, -0.48, 0.67, and -0.74,
respectively). Significant factors for depressive symptoms included family
status, employment before retirement, homemaking, reading, aluminum utensil use,
dietary restriction, and hypertension (regression coefficients: 3.09, -1.33,
1.62, -1.31, 0.96, -1.15, and 1.14, respectively). CONCLUSION: These findings
indicated that cognition was negatively associated with depression in patients
with AD, and both were influenced by reading, aluminum utensil use, dietary
restriction, and hypertension. Considering patient factors may help to slow the
progression of dementia.
PMID- 28514666
TI - A Temporal Proteomic Map of Epstein-Barr Virus Lytic Replication in B Cells.
AB - Epstein-Barr virus (EBV) replication contributes to multiple human diseases,
including infectious mononucleosis, nasopharyngeal carcinoma, B cell lymphomas,
and oral hairy leukoplakia. We performed systematic quantitative analyses of
temporal changes in host and EBV proteins during lytic replication to gain
insights into virus-host interactions, using conditional Burkitt lymphoma models
of type I and II EBV infection. We quantified profiles of >8,000 cellular and 69
EBV proteins, including >500 plasma membrane proteins, providing temporal views
of the lytic B cell proteome and EBV virome. Our approach revealed EBV-induced
remodeling of cell cycle, innate and adaptive immune pathways, including
upregulation of the complement cascade and proteasomal degradation of the B cell
receptor complex, conserved between EBV types I and II. Cross-comparison with
proteomic analyses of human cytomegalovirus infection and of a Kaposi-sarcoma
associated herpesvirus immunoevasin identified host factors targeted by multiple
herpesviruses. Our results provide an important resource for studies of EBV
replication.
PMID- 28514671
TI - Evaluation of improved IS6110 LAMP assay for diagnosis of pulmonary and extra
pulmonary tuberculosis.
AB - In the present study, IS6110 loop mediated isothermal amplification (LAMP) assay
was modified using dUTP-UNG (uracil-DNA N-glycosylase) strategy to prevent
carryover contamination, and was evaluated using clinical specimens. The clinical
specimens were collected from 236 suspected patients of pulmonary tuberculosis
and 315 specimens of suspected patients of extra pulmonary tuberculosis. DNA was
extracted from specimens and used as template for nucleic acid amplification. The
results were evaluated with culture method as gold standard. Modified IS6110 LAMP
assay showed high sensitivity (94.4%) and specificity (97.2%) in specimens
collected from suspected pulmonary tuberculosis patients. Sensitivity was
comparatively less (86.67%) in extra pulmonary specimens while specificity was
94.04%. In conclusion, IS6110 LAMP assay was modified to prevent carry over
contamination and it was validated to be rapid, sensitive and specific method
with prospective application in resource-limited settings.
PMID- 28514670
TI - Radiation Safety in Children With Congenital and Acquired Heart Disease: A
Scientific Position Statement on Multimodality Dose Optimization From the Image
Gently Alliance.
AB - There is a need for consensus recommendations for ionizing radiation dose
optimization during multimodality medical imaging in children with congenital and
acquired heart disease (CAHD). These children often have complex diseases and may
be exposed to a relatively high cumulative burden of ionizing radiation from
medical imaging procedures, including cardiac computed tomography, nuclear
cardiology studies, and fluoroscopically guided diagnostic and interventional
catheterization and electrophysiology procedures. Although these imaging
procedures are all essential to the care of children with CAHD and have
contributed to meaningfully improved outcomes in these patients, exposure to
ionizing radiation is associated with potential risks, including an increased
lifetime attributable risk of cancer. The goal of these recommendations is to
encourage informed imaging to achieve appropriate study quality at the lowest
achievable dose. Other strategies to improve care include a patient-centered
approach to imaging, emphasizing education and informed decision making and
programmatic approaches to ensure appropriate dose monitoring. Looking ahead,
there is a need for standardization of dose metrics across imaging modalities, so
as to encourage comparative effectiveness studies across the spectrum of CAHD in
children.
PMID- 28514672
TI - Biochemical Underpinnings of Immune Cell Metabolic Phenotypes.
AB - The metabolism of immune cells affects their function and influences host
immunity. This review explores how immune cell metabolic phenotypes reflect
biochemical dependencies and highlights evidence that both the metabolic state of
immune cells and nutrient availability can alter immune responses. The central
importance of oxygen, energetics, and redox homeostasis in immune cell
metabolism, and how these factors are reflected in different metabolic
phenotypes, is also discussed. Linking immune cell metabolic phenotype to
effector functions is important to understand how altering metabolism can impact
the way in which immune cells meet their metabolic demands and affect the immune
response in various disease contexts.
PMID- 28514676
TI - Human ILC1: To Be or Not to Be.
PMID- 28514674
TI - MenTORing Immunity: mTOR Signaling in the Development and Function of Tissue
Resident Immune Cells.
AB - Tissue-resident immune cells must balance survival in peripheral tissues with the
capacity to respond rapidly upon infection or tissue damage, and in turn couple
these responses with intrinsic metabolic control and conditions in the tissue
microenvironment. The serine/threonine kinase mammalian/mechanistic target of
rapamycin (mTOR) is a central integrator of extracellular and intracellular
growth signals and cellular metabolism and plays important roles in both innate
and adaptive immune responses. This review discusses the function of mTOR
signaling in the differentiation and function of tissue-resident immune cells,
with focus on the role of mTOR as a metabolic sensor and its impact on metabolic
regulation in innate and adaptive immune cells. We also discuss the impact of
metabolic constraints in tissues on immune homeostasis and disease, and how
manipulating mTOR activity with drugs such as rapamycin can modulate immunity in
these contexts.
PMID- 28514677
TI - Human Group 1 Innate Lymphocytes Are Negative for Surface CD3epsilon but Express
CD5.
PMID- 28514673
TI - Metabolic and Epigenetic Coordination of T Cell and Macrophage Immunity.
AB - Recognition of pathogens by innate and adaptive immune cells instructs rapid
alterations of cellular processes to promote effective resolution of infection.
To accommodate increased bioenergetic and biosynthetic demands, metabolic
pathways are harnessed to maximize proliferation and effector molecule
production. In parallel, activation initiates context-specific gene-expression
programs that drive effector functions and cell fates that correlate with changes
in epigenetic landscapes. Many chromatin- and DNA-modifying enzymes make use of
substrates and cofactors that are intermediates of metabolic pathways, providing
potential cross talk between metabolism and epigenetic regulation of gene
expression. In this review, we discuss recent studies of T cells and macrophages
supporting a role for metabolic activity in integrating environmental signals
with activation-induced gene-expression programs through modulation of the
epigenome and speculate as to how this may influence context-specific macrophage
and T cell responses to infection.
PMID- 28514678
TI - Toward Meaningful Definitions of Innate-Lymphoid-Cell Subsets.
PMID- 28514679
TI - Size Doesn't Matter: Shorter Antibody Loops Can Infiltrate HIV's Env Apex
Defenses.
AB - An HIV vaccine that elicits broadly neutralizing antibodies, which often have
unusual structural features, has not yet been developed. In Immunity this month,
Cale et al., 2017 describe how a new mode of binding allows a conventional
antibody to infiltrate HIV's armor.
PMID- 28514675
TI - Metabolic Regulation of the Immune Humoral Response.
AB - Productive humoral responses require that naive B cells and their differentiated
progeny move among distinct micro-environments. In this review, we discuss how
studies are beginning to address the nature of these niches as well as the
interplay between cellular signaling, metabolic programming, and adaptation to
the locale. Recent work adds evidence to the expectation that B cells at distinct
stages of development or functional subsets are influenced by the altered
profiles of nutrients and metabolic by-products that distinguish these sites.
Moreover, emerging findings reveal a cross-talk among the external milieu, signal
transduction pathways, and transcription factors that direct B cell fate in the
periphery.
PMID- 28514680
TI - Understanding Spontaneous Conversion: The Case of the Ly6C- Monocyte.
AB - Mouse blood monocytes include two main subsets usually discriminated by the
expression of the Ly6C surface marker. The study by Mildner et al. (2017) in this
issue of Immunity clarifies the transcriptional circuits controlling the
generation of Ly6C- cells from their obligate precursors, the Ly6C+ monocytes.
PMID- 28514681
TI - Only Two Can Tango: Mast Cells Displace Epithelial Cells to Dance with ILC2s.
AB - Mast cells have been implicated in protective immunity to helminth infection, but
the precise mechanism remains unclear. In this issue of Immunity, Shimokawa et
al., 2017 report that mast cells are a bridge linking dying epithelial cells with
effector type 2 innate lymphoid cells.
PMID- 28514682
TI - You Can Breathe Easy: IFNlambda Handles Flu without Triggering a Damaging
Inflammatory Response.
AB - Type III interferon (IFNlambda) and type I IFN (IFNalpha/beta) have overlapping
antiviral activities in the lung. In this issue of Immunity, Galani et al. (2017)
identify a critical early role for IFNlambda, not shared by IFNalpha/beta, in
protection of the lung following influenza virus infection.
PMID- 28514683
TI - Dengue Antibodies, then Zika: A Fatal Sequence in Mice.
AB - Anti-Dengue virus (DENV) antibodies can be either protective or pathogenic in
humans with prior DENV infection. In a recent issue of Science, Bardina et al.
(2017) demonstrated that passive transfer of immune plasma against DENV and West
Nile virus (WNV) can enhance Zika virus (ZIKV) infection and pathogenesis in
mice.
PMID- 28514684
TI - CD4+ T Cell Activation and Vascular Normalization: Two Sides of the Same Coin?
AB - Normalization of tumor blood vessels enhances the infiltration and functions of T
cells. Tian et al. (2017) report that effector CD4+ T cells, in turn, support
vascular normalization, highlighting intertwined roles for blood vessels and T
cells in cancer.
PMID- 28514686
TI - Glycine Substitution at Helix-to-Coil Transitions Facilitates the Structural
Determination of a Stabilized Subtype C HIV Envelope Glycoprotein.
AB - Advances in HIV-1 envelope glycoprotein (Env) design generate native-like trimers
and high-resolution clade A, B, and G structures and elicit neutralizing
antibodies. However, a high-resolution clade C structure is critical, as this
subtype accounts for the majority of HIV infections worldwide, but well-ordered
clade C Env trimers are more challenging to produce due to their instability.
Based on targeted glycine substitutions in the Env fusion machinery, we defined a
general approach that disfavors helical transitions leading to post-fusion
conformations, thereby favoring the pre-fusion state. We generated a stabilized,
soluble clade C Env (16055 NFL) and determined its crystal structure at 3.9 A.
Its overall conformation is similar to SOSIP.664 and native Env trimers but
includes a covalent linker between gp120 and gp41, an engineered 201-433
disulfide bond, and density corresponding to 22 N-glycans. Env-structure-guided
design strategies resulted in multiple homogeneous cross-clade immunogens with
the potential to advance HIV vaccine development.
PMID- 28514685
TI - Virus-like Particles Identify an HIV V1V2 Apex-Binding Neutralizing Antibody that
Lacks a Protruding Loop.
AB - Most HIV-1-specific neutralizing antibodies isolated to date exhibit unusual
characteristics that complicate their elicitation. Neutralizing antibodies that
target the V1V2 apex of the HIV-1 envelope (Env) trimer feature unusually long
protruding loops, which enable them to penetrate the HIV-1 glycan shield. As
antibodies with loops of requisite length are created through uncommon
recombination events, an alternative mode of apex binding has been sought. Here,
we isolated a lineage of Env apex-directed neutralizing antibodies, N90-VRC38.01
11, by using virus-like particles and conformationally stabilized Env trimers as
B cell probes. A crystal structure of N90-VRC38.01 with a scaffolded V1V2
revealed a binding mode involving side-chain-to-side-chain interactions that
reduced the distance the antibody loop must traverse the glycan shield, thereby
facilitating V1V2 binding via a non-protruding loop. The N90-VRC38 lineage thus
identifies a solution for V1V2-apex binding that provides a more conventional B
cell pathway for vaccine design.
PMID- 28514687
TI - Particulate Array of Well-Ordered HIV Clade C Env Trimers Elicits Neutralizing
Antibodies that Display a Unique V2 Cap Approach.
AB - The development of soluble envelope glycoprotein (Env) mimetics displaying
ordered trimeric symmetry has ushered in a new era in HIV-1 vaccination. The
recently reported native, flexibly linked (NFL) design allows the generation of
native-like trimers from clinical isolates at high yields and homogeneity. As the
majority of infections world-wide are of the clade C subtype, we examined
responses in non-human primates to well-ordered subtype C 16055 trimers
administered in soluble or high-density liposomal formats. We detected superior
germinal center formation and enhanced autologous neutralizing antibodies against
the neutralization-resistant (tier 2) 16055 virus following inoculation of
liposome-arrayed trimers. Epitope mapping of the neutralizing monoclonal
antibodies (mAbs) indicated major contacts with the V2 apex, and 3D electron
microscopy reconstructions of Fab-trimer complexes revealed a horizontal binding
angle to the Env spike. These vaccine-elicited mAbs target the V2 cap,
demonstrating a means to accomplish tier 2 virus neutralization by penetrating
the dense N-glycan shield.
PMID- 28514689
TI - Identification of a Human Clonogenic Progenitor with Strict Monocyte
Differentiation Potential: A Counterpart of Mouse cMoPs.
AB - Monocytes give rise to macrophages and dendritic cells (DCs) under steady-state
and inflammatory conditions, thereby contributing to host defense and tissue
pathology. A common monocyte progenitor (cMoP) that is strictly committed to the
monocyte lineage has been recently identified in mice. Here, we identified human
cMoPs as a CLEC12AhiCD64hi subpopulation of conventional granulocyte-monocyte
progenitors (cGMPs) in umbilical cord blood and in bone marrow. Human cMoPs gave
rise to monocyte subsets without showing any potential for differentiating into
myeloid or lymphoid cells. Within the cGMP population, we also identified revised
GMPs that completely lacked DC and lymphoid potential. Collectively, our findings
expand and revise the current understanding of human myeloid cell differentiation
pathways.
PMID- 28514688
TI - The E-Id Protein Axis Specifies Adaptive Lymphoid Cell Identity and Suppresses
Thymic Innate Lymphoid Cell Development.
AB - Innate and adaptive lymphoid development is orchestrated by the activities of E
proteins and their antagonist Id proteins, but how these factors regulate early T
cell progenitor (ETP) and innate lymphoid cell (ILC) development remains unclear.
Using multiple genetic strategies, we demonstrated that E proteins E2A and HEB
acted in synergy in the thymus to establish T cell identity and to suppress the
aberrant development of ILCs, including ILC2s and lymphoid-tissue-inducer-like
cells. E2A and HEB orchestrated T cell fate and suppressed the ILC transcription
signature by activating the expression of genes associated with Notch receptors,
T cell receptor (TCR) assembly, and TCR-mediated signaling. E2A and HEB acted in
ETPs to establish and maintain a T-cell-lineage-specific enhancer repertoire,
including regulatory elements associated with the Notch1, Rag1, and Rag2 loci. On
the basis of these and previous observations, we propose that the E-Id protein
axis specifies innate and adaptive lymphoid cell fate.
PMID- 28514690
TI - Genomic Characterization of Murine Monocytes Reveals C/EBPbeta Transcription
Factor Dependence of Ly6C- Cells.
AB - Monocytes are circulating, short-lived mononuclear phagocytes, which in mice and
man comprise two main subpopulations. Murine Ly6C+ monocytes display
developmental plasticity and are recruited to complement tissue-resident
macrophages and dendritic cells on demand. Murine vascular Ly6C- monocytes patrol
the endothelium, act as scavengers, and support vessel wall repair. Here we
characterized population and single cell transcriptomes, as well as enhancer and
promoter landscapes of the murine monocyte compartment. Single cell RNA-seq and
transplantation experiments confirmed homeostatic default differentiation of
Ly6C+ into Ly6C- monocytes. The main two subsets were homogeneous, but linked by
a more heterogeneous differentiation intermediate. We show that monocyte
differentiation occurred through de novo enhancer establishment and activation of
pre-established (poised) enhancers. Generation of Ly6C- monocytes involved
induction of the transcription factor C/EBPbeta and C/EBPbeta-deficient mice
lacked Ly6C- monocytes. Mechanistically, C/EBPbeta bound the Nr4a1 promoter and
controlled expression of this established monocyte survival factor.
PMID- 28514691
TI - Mast Cells Are Crucial for Induction of Group 2 Innate Lymphoid Cells and
Clearance of Helminth Infections.
AB - Mast cells are important for eradication of intestinal nematodes; however, their
precise mechanisms of action have remained elusive, especially in the early phase
of infection. We found that Spi-B-deficient mice had increased numbers of mast
cells and rapidly expelled the Heligmosomoides polygyrus (Hp) nematode. This was
accompanied by induction of interleukin-13 (IL-13)-producing group 2 innate
lymphoid cells (ILC2) and goblet cell hyperplasia. Immediately after Hp
infection, mast cells were rapidly activated to produce IL-33 in response to ATP
released from apoptotic intestinal epithelial cells. In vivo inhibition of the
P2X7 ATP receptor rendered the Spi-B-deficient mice susceptible to Hp,
concomitant with elimination of mast cell activation and IL-13-producing ILC2
induction. These results uncover a previously unknown role for mast cells in
innate immunity in that activation of mast cells by ATP orchestrates the
development of a protective type 2 immune response, in part by producing IL-33,
which contributes to ILC2 activation.
PMID- 28514692
TI - Interferon-lambda Mediates Non-redundant Front-Line Antiviral Protection against
Influenza Virus Infection without Compromising Host Fitness.
AB - Lambda interferons (IFNlambdas) or type III IFNs share homology, expression
patterns, signaling cascades, and antiviral functions with type I IFNs. This has
complicated the unwinding of their unique non-redundant roles. Through the
systematic study of influenza virus infection in mice, we herein show that
IFNlambdas are the first IFNs produced that act at the epithelial barrier to
suppress initial viral spread without activating inflammation. If infection
progresses, type I IFNs come into play to enhance viral resistance and induce pro
inflammatory responses essential for confronting infection but causing
immunopathology. Central to this are neutrophils which respond to both cytokines
to upregulate antimicrobial functions but exhibit pro-inflammatory activation
only to type I IFNs. Accordingly, Ifnlr1-/- mice display enhanced type I IFN
production, neutrophilia, lung injury, and lethality, while therapeutic
administration of PEG-IFNlambda potently suppresses these effects. IFNlambdas
therefore constitute the front line of antiviral defense in the lung without
compromising host fitness.
PMID- 28514693
TI - Drinking despite health problems among individuals with liver disease across the
United States.
AB - BACKGROUND: Heavy drinking is harmful for individuals with liver disease.
However, some of these individuals drink despite knowledge of the risks. The
current study aims to identify factors underlying drinking despite health
problems among individuals with liver disease. METHODS: The current study
utilizes a subsample of individuals reporting past-year liver disease and at
least one drink in the past year (n=331), taken from the National Epidemiologic
Survey on Alcohol and Related Conditions-III (NESARC-III), a large nationally
representative survey of the United States. Participants reported on drinking
despite health problems, symptoms of psychopathology, and family history of
alcohol problems in a cross-sectional survey. RESULTS: Drug use disorders
(Adjusted Odds Ratio [AOR]=2.68), as well as borderline, antisocial, and
schizotypal personality disorders (AORs=2.50-4.10), were associated with
increased likelihood of drinking despite health problems among individuals with
liver disease, all ps<0.05. Any anxiety disorder trended toward significance
(AOR=2.22), p=0.06, but major depressive disorder was not associated with
increased risk, (AOR=0.99), ps=0.97. Individuals with a family history of alcohol
problems were also more likely to drink despite health problems (AOR=2.79),
p<0.05. CONCLUSIONS: Several types of psychopathology, as well as a family
history of alcohol problems, increased the likelihood of drinking despite health
problems among individuals with liver disease. These findings highlight the need
to intervene with heavily drinking individuals with liver disease, who may be
drinking due to familial risk and/or comorbid psychopathology.
PMID- 28514694
TI - The association of prenatal cocaine exposure, externalizing behavior and
adolescent substance use.
AB - Prenatal cocaine exposure (PCE) may increase adolescent substance use through
alterations of neurotransmitter systems affecting fetal brain development. The
relationship between PCE and substance use at 15 and 17 years was examined.
Subjects (365: 186 PCE; 179 non-cocaine exposed (NCE)) supplied biologic and self
report data using the Youth Risk Behavior Surveillance System (YRBSS) and
Computerized Diagnostic Interview Schedule for Children (C-DISC 4) at ages 15 and
17. The relationship between PCE and substance use was assessed using General
Estimating Equation (GEE) analyses controlling for confounding factors including
violence exposure and preschool lead level. Teens with PCE vs. NCE teens were 2
times more likely to use tobacco (OR=2.1; 95% CI 1.21-3.63; p<.001) and marijuana
(OR=1.85; CI 1.18-2.91; p<.001) and have a substance use disorder at age 17
(OR=2.51; CI 1.00-6.28; p<.05). Evaluation of PCE status by gender revealed an
association between PCE and marijuana use that was more pronounced for boys than
girls at 17 years. Violence exposure was also a significant predictor of alcohol
(p<.001), tobacco (p<.05), and marijuana (p<.0006) use and substance
abuse/dependence (p<.01). Externalizing behavior at age 12 fully mediated the
effects of PCE on substance use disorder at age 17 and partially mediated effects
of PCE on tobacco use, but did not mediate effects on marijuana use. The
percentage of substance use reported increased between 15 and 17 years, with no
differences between the PCE and NCE groups. Data suggest specialized drug use
prevention measures for children with PCE may benefit this high risk group.
PMID- 28514695
TI - New product trial, use of edibles, and unexpected highs among marijuana and
hashish users in Colorado.
AB - OBJECTIVE: This study examines the relationships between trial of new marijuana
or hashish products and unexpected highs, and use of edible products and
unexpected highs. METHODS: We conducted an online survey of 634 adult, past-year
marijuana users in Colorado. We used logistic regression models to examine the
relationship between new product trial or edible use and unexpected highs.
RESULTS: In the first year that recreational marijuana was legal in Colorado,
71.4% of respondents tried a new marijuana or hashish product, and 53.6% used an
edible product. Trial of new products was associated with greater odds of
experiencing an unexpected high after controlling for age, gender, education,
mental health status, current marijuana or hashish use, and mean amount of
marijuana or hashish consumed in the past month (OR=2.13, p<0.001). Individuals
who reported having used edibles had greater odds of experiencing an unexpected
high, after controlling for the same set of variables (OR=1.56, p<0.05).
CONCLUSION: People who try new marijuana or hashish products, or use edible
marijuana or hashish products, are at greater risk for an unexpected high. It is
possible that some negative outcomes associated with marijuana use and unexpected
highs may be averted through a better understanding of how to use product
packaging to communicate with consumers.
PMID- 28514696
TI - Alcohol use disorders in Iran: Prevalence, symptoms, correlates, and comorbidity.
AB - BACKGROUND: For nearly four decades, alcohol production and consumption has been
banned in the Islamic country of Iran. However, little is known about the extent
of alcohol use and associated problems in the country. The paper aims to present
findings on the 12-month prevalence, symptoms, severity, correlates, and
comorbidity of alcohol use disorders in the Iranian population. METHODS: This
report is based on the 2011 Iranian household Mental Health survey (IranMHS), a
nationally representative face-to-face household survey with a multi-stage,
cluster sampling design. A total of 7840 individuals aged 15-64 responded to the
alcohol section. We assessed 12-month alcohol use disorders according to DSM-IV
and DSM-5 criteria and harmful use according to the ICD-10 criteria. RESULTS:
Weighted prevalence of using alcohol at least once in the past 12 months was
5.7%. The prevalence of 12-month alcohol use disorders was 1% according to DSM-IV
criteria and 1.3% according to DSM-5. Harmful use was reported in 0.6%. Alcohol
use disorders were markedly more common in men than women with an odds ratio (OR)
of 13.3. It was also more prevalent in never-married versus married individuals
(OR=2.5) and in those living in urban versus rural areas (OR=2.4). Among those
with alcohol use disorders, 46.3% had a concurrent mood or anxiety disorder.
Aggressive behaviors and injuries were more likely in those with alcohol use
disorders. CONCLUSION: Although Iran has a low level of alcohol use, its adverse
consequences including use disorders, aggression, and injuries are moderately
common and raise serious public health concerns.
PMID- 28514697
TI - Lipoprotein-associated phospholipase A2 and risks of coronary heart disease and
ischemic stroke in the general population: A systematic review and meta-analysis.
AB - BACKGROUND: This study investigated the associations between lipoprotein
associated phospholipase A2 (Lp-PLA2) and the risks of coronary heart disease
(CHD) and ischemic stroke (IS) in the general population. METHODS: PubMed,
Embase, and the Cochrane Library databases were searched for prospective cohort
studies published prior to June 2016. Multivariate-adjusted hazard ratios (HRs)
with 95% confidence intervals (CIs) for CHD and IS risks according to Lp-PLA2
activity or mass were extracted, pooled, and weighted using random-effects
modeling. RESULTS: Twelve studies examining Lp-PLA2 activity or mass and long
term risks of CHD and IS were included. Combined HRs for CHD and IS risks for the
highest category referring to lowest category of Lp-PLA2 were 1.46 (95% CI: 1.20
1.78, P<0.001) and 1.58 (95% CI: 1.21-2.07, P=0.001), respectively. The same
patterns were observed for both mass and activity, with the exception of those
for CHD. For every 1-standard deviation (SD) increase in Lp-PLA2 activity, CHD
risk increased by 12% (HR: 1.12, 95% CI: 1.05-1.22, P=0.002); no association
between 1-SD increases in Lp-PLA2 activity and IS was observed. Lp-PLA2 mass was
associated with CHD risk (HR: 1.02-1.24, 95% CI: 1.02-1.24, P=0.021). Lp-PLA2
mass per 1-SD increase was not associated with IS risk. CONCLUSIONS: Greater Lp
PLA2 activity or mass was associated with an increased risk of CHD and IS;
however, additional well-designed trials are warranted to confirm this
association.
PMID- 28514698
TI - Clinical outcomes and frontal plane two-dimensional biomechanics during the 30
second single leg stance test in patients before and after hip abductor tendon
reconstructive surgery.
AB - BACKGROUND: Hip abductor tendon tears are a common cause of Greater Trochanteric
Pain Syndrome. Conservative treatments are often ineffective and surgical
reconstruction may be recommended. This study investigated the improvement in
clinical outcomes and frontal plane two-dimensional biomechanics during a 30
second single leg stance test, in patients undergoing reconstruction. We
hypothesized that clinical scores and pertinent biomechanical variables would
significantly improve post-surgery, and these outcomes would be significantly
correlated. METHODS: Twenty-one patients with symptomatic tendon tears underwent
reconstruction. Patients were evaluated pre-surgery, and at 6 and 12months post
surgery, using patient-reported outcome measures, assessment of hip abductor
strength and six-minute walk capacity. Frontal plane, two-dimensional,
biomechanical variables including pelvis-on-femur angle, pelvic drop, trunk lean
and lateral pelvic shift, were evaluated throughout a 30-second single leg stance
test. ANOVA evaluated outcomes over time, while Pearson's correlations
investigated associations between clinical scores, pain, functional and
biomechanical outcome variables. FINDINGS: While clinical and functional measures
significantly improved (P<0.05) over time, no significant group differences
(P>0.05) were observed in biomechanical variables from pre- to post-surgery.
While five patients displayed a positive Trendelenburg sign pre-surgery, only one
was positive post-surgery. Clinical outcomes and biomechanical variables during
the single leg stance test were not correlated. INTERPRETATION: Despite
improvements in clinical and functional measures over time, biomechanical changes
during a weight bearing single leg stance test were not significantly different
following tendon repair. Follow up beyond 12months may be required, whereby
symptomatic relief may precede functional and biomechanical improvement.
PMID- 28514699
TI - Profiling of illicit cocaine seized in China by ICP-MS analysis of inorganic
elements.
AB - For the first time in China, the inorganic element profiling of cocaine specimens
was performed at the National Narcotics Laboratory. An inductive coupled plasma
mass spectrometry (ICP-MS) method was developed and validated for simultaneous
analysis of 26 inorganic elements, including sodium (Na), magnesium (Mg),
aluminuim (Al), potassium (K), calcium (Ca), vanadium (V), chromium (Cr),
manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn),
arsenic (As), selenium (Se), molybdenum (Mo), silver (Ag), cadmium (Cd), antimony
(Sb), barium (Ba), lanthanum (La), cerium (Ce), thallium (Tl), lead (Pb), thorium
(Th), and uranium (U) in illicit cocaine samples. Ultrasonic assisted dissolution
was applied for sample preparation. Minimum sample preparation and analysis time
were required, which was suitable for routine analysis. After the analysis of 183
cocaine samples seized from 2011 to 2015, the element concentration ranges of
cocaine sample were obtained. Based on the quantitative data set of 26 inorganic
elements in 131 linked/un-linked cocaine samples, fifty combinations of pre
treatment methods and distance/correlation measurements were tested for their
potential discrimination power for cocaine profiling, and
normalization+standardization+logarithm (N+S+L)/Cosine correlation exhibited the
best result. After hierarchical cluster analysis (HCA) analysis of 183 cocaine
samples, 21 groups of linked samples were found within and between provinces,
which provide intelligence for case connection and revealing of the distribution
networks.
PMID- 28514700
TI - A comparative in situ decomposition study using still born piglets and leaf
litter from a deciduous forest.
AB - A cadaver and dead plant organic matter, or litter, are rich energy sources that
undergo a complex decomposition process, which impact the surrounding
environmental microbiota. Advances in molecular microbiology techniques, with
study of the 16S RNA genes, in particular, have highlighted the application of
forensic ecogenomics in addressing key knowledge gaps. To investigate subsurface
microbiome shifts as a novel tool to establish "postmortem microbial clock" and
augment postmortem interval (PMI) and time-since-burial estimations, an in situ
study with triplicate underground burials of piglets as human taphonomic proxies
and Quercus robur leaf litter was monitored for 270 days. Changes in microbial
community structure and composition were related directly to changes in seasonal
temperature, with microbial shifts more pronounced during the summer. For
example, Methylococcaceae could be used as seasonal bacterial indicators, from
winter to summer, in establishing postmortem microbial clock for this site.
Furthermore, Methylophilaceae (Methylophilales order) and Anaerolineaceae would
differentiate for the piglet and leaf litter soils, respectively, 180 days after
internment.
PMID- 28514701
TI - A biased opinion: Demonstration of cognitive bias on a fingerprint matching task
through knowledge of DNA test results.
AB - One study is presented which explores the biasing effects of irrelevant
contextual information on a fingerprint matching task. Bias was introduced by
providing the outcomes of a DNA test relating to each fictitious case under
consideration. This was engineered to suggest either a match, no match, or an
inconclusive outcome, and was thus either consistent, misleading or unbiased
depending on the ground truth of each fingerprint pair. The results suggested
that, when the difficulty of the fingerprint matching task was measurably
increased, participants became more vulnerable to the biasing information. Under
such conditions, when performance was good, misleading evidence lowered accuracy,
and when performance was weaker, consistent evidence improved accuracy. As such,
the results confirmed existing demonstrations of cognitive bias from contextual
information in the fingerprint task. Moreover, by taking a process-based
approach, it became possible to articulate the concerns, and the potential
solutions, at each stage of the workflow. The results offer value for the
forensic science community in extending the evidence-base regarding cognitive
bias, and in articulating routes to improve the credibility of fingerprint
decisions.
PMID- 28514702
TI - Nanoscale morphological analysis of soft matter aggregates with fractal dimension
ranging from 1 to 3.
AB - While the widespread emergence of nanoscience and nanotechnology can be dated
back to the early eighties, the last decade has witnessed a true coming of age of
this research field, with novel nanomaterials constantly finding their way into
marketed products. The performance of nanomaterials being dominated by their
nanoscale morphology, their quantitative characterization with respect to a
number of properties is often crucial. In this context, those imaging techniques
able to resolve nanometer scale details are clearly key players. In particular,
atomic force microscopy can yield a fully quantitative tridimensional (3D)
topography at the nanoscale. Herein, we will review a set of morphological
analysis based on the scaling approach, which give access to important
quantitative parameters for describing nanomaterial samples. To generalize the
use of such morphological analysis on all D-dimensions (1D, 2D and 3D), the
review will focus on specific soft matter aggregates with fractal dimension
ranging from just above 1 to just below 3.
PMID- 28514703
TI - Bacterial infections and hepatic encephalopathy in liver cirrhosis-prophylaxis
and treatment.
AB - Infections are common among patients with liver cirrhosis. They occur more often
in cirrhotic patient groups than in the general population and result in higher
mortality. One reason for this phenomenon is bacterial translocation from the
intestinal lumen that occurs as a consequence of intestinal bacterial overgrowth,
increased permeability and decreased motility. The most common infections in
cirrhotic patients are spontaneous bacterial peritonitis and urinary tract
infections, followed by pneumonia, skin and soft tissue infections. Intestinal
bacterial overgrowth is also responsible for hyperammonemia, which leads to
hepatic encephalopathy. All of these complications make this group of patients at
high risk for mortality. The role of antibiotics in liver cirrhosis is to treat
and in some cases to prevent the development of infectious complications. Based
on our current knowledge, antibiotic prophylaxis should be administered to
patients with gastrointestinal hemorrhage, low ascitic fluid protein
concentration combined with liver or renal failure, and spontaneous bacterial
peritonitis as a secondary prophylaxis, as well as after hepatic encephalopathy
episodes (also as a secondary prophylaxis). In some cases, the use of non
antibiotic prophylaxis can also be considered. Current knowledge of the treatment
of infections allows the choice of a preferred antibiotic for empiric therapy
depending on the infection location and whether the source of the disease is
nosocomial or community-acquired.
PMID- 28514704
TI - Guillain-Barre Syndrome, variants & forms fruste: Reclassification with new
criteria.
AB - OBJECTIVES: This study aimed to evaluate the clinical and electrophysiological
characteristics of various distinctive classical and localised Guillain-Barre
syndrome (GBS) subtypes. PATIENTS AND METHODS: Clinical characteristics and
electrophysiological data of sixty-one consecutive patients admitted between 2012
and 2015 were systematically analysed and reclassified according to the new GBS
clinical classification. Neurophysiology was evaluated with Hadden et al.'s vs
recently proposed Rajabally et al.'s criteria. Functional severity and clinical
outcome of various GBS subtypes were ascertained. RESULTS: All patients initially
identified as GBS or related disorders can be sub-classified into having
classical GBS (41, 67%), classic Miller-Fisher Syndrome (MFS) (6, 10%),
Pharyngeal-cervical-brachial (PCB) (3, 5%), paraparetic GBS (4, 7%), bifacial
weakness with paresthesia (3, 5%), acute ophthalmoparesis (AO) (1, 2%) and
overlap syndrome (3, 5%): one (2%) with GBS/Bickerstaff brainstem encephalitis
overlap and 2 (3%) with GBS/MFS overlap. Greater proportion of axonal classical
GBS (67% vs 55%, p=0.372) seen with Rajabally et al.'s criteria and a
predominantly axonal form of paraparetic variant (75%) independent of
electrodiagnostic criteria were more representative of Asian GBS cohort.
Classical GBS patients had lowest admission and discharge Medical Research
Council Sum Score (MRCSS), greater functional disability and longest length of in
patient stay. Twenty (20/21, 95%) patients who needed mechanical ventilation had
classical GBS. Patients required repeated dose of intravenous immunoglobulin
(5/6, 3%) or plasma exchange (4/4, 100%) more frequently had axonal form of
classical GBS. CONCLUSION: Phenotype recognition based on new GBS clinical
classification, supported by electrodiagnostic study permits more precise
clinical subtypes determination and outcome prognostication.
PMID- 28514705
TI - A topologically diverse family of fluoride channels.
AB - Dual-topology proteins are likely evolutionary antecedents to a common motif in
membrane protein structures, the inverted repeat. A family of fluoride channels,
the Flucs, which protect microorganisms, fungi, and plants against cytoplasmic
fluoride accumulation, has representatives of all topologies along this
evolutionary trajectory, including dual-topology homodimers, antiparallel
heterodimers, and, in eukaryotes, fused two-domain proteins with an inverted
repeat motif. Recent high-resolution crystal structures of dual-topology
homodimers, coupled with extensive functional information about both the
homodimers and two-domain Flucs, provide a case study of the co-evolution of fold
and function.
PMID- 28514707
TI - Influence of fumigants on sunflower seeds: Characteristics of fumigant desorption
and changes in volatile profiles.
AB - Fumigation of transport containers is common practice to protect stored products
from pests. Yet little is known about the desorption times and effects of the
highly toxic gases used in this process. To shed light on the behavior of
fumigants in real food, we treated sunflower seeds (Helianthus annuus L.) with
100ppm phosphine (PH3), methyl bromide (MeBr) or 1,2-dichloroethane (DCE) for
72h. The compound concentrations in the air were then analyzed by thermal
desorption/2D gas chromatography coupled to mass spectrometry and flame
photometric detection (TD-2D-GC-MS/FPD). A desorption time of several months was
observed for DCE, whereas PH3 and MeBr were outgassed in a matter of days. To
investigate possible interactions between gases and constituents of the seeds,
non-fumigated, fumigated and outgassed samples were analyzed by headspace solid
phase microextraction GC-MS. We observed significantly different volatile
profiles in fumigated and subsequently outgassed seeds compared to non-fumigated
seeds. Whereas PH3-treated seeds released far more terpenoids, the volatile
pattern of seeds exposed to DCE revealed significantly fewer terpenoids but more
aldehydes. These changes are likely to affect food aroma characteristics.
PMID- 28514706
TI - Evaluation of behavioral change after adenotonsillectomy for obstructive sleep
apnea in children with autism spectrum disorder.
AB - BACKGROUND AND OBJECTIVE: Obstructive sleep apnea (OSA) may affect daily
cognitive functioning in children. The aims of our study were two-fold. The first
aim was to detect, using the Child Behavior Checklist (CBCL), whether
adenotonsillectomy (AT) for the treatment of OSA improved the behavior of
children with autism spectrum disorder (ASD). The second aim was to identify
characteristics for behavioral improvement following the treatment of OSA in
these children with ASD. METHODS: The behaviors of ASD children aged 5-14 years
diagnosed as having OSA (n=30) were evaluated using CBCL before and after AT.
CBCL evaluation of ASD children without OSA at two time points with the same
interval served as a control (n=24). We statistically examined the two groups. In
addition, we conducted a paired t-test to assess changes in CBCL Tscores between
the improved group and unchanged/deteriorated group to identify characteristics
that may affect behavioral changes following OSA treatment. RESULTS: After AT, T
scores of the CBCL scales were significantly improved in the OSA group, but no
change was observed in the control. A paired t-test revealed that the improved
group had significantly higher scores on the CBCL pre-AT than the
unchanged/deteriorated group in ASD children with OSA after OSA treatment.
CONCLUSIONS: Behavioral problems were significantly improved following AT in ASD
children with OSA. Early detection and treatment of children with OSA is
essential to prevent behavioral problems and to support mental development.
PMID- 28514708
TI - The effect of lamb carcase weight and GR depth on the production of value-added
cuts - A short communication.
AB - Times for the progressive breakdown of 95 lamb carcases were recorded to
determine the impact of carcase weight and GR tissue depth on the time and
therefore cost to produce value added retail cuts. Further analysis also assessed
the potential to use these carcase traits as predictors of fabrication times.
Regression modeling demonstrated there was a limited ability to predict the
difference in time to fabricate mid value-added (R2=0.18) and extreme value-added
(R2=0.12) cuts compared to traditional cuts, suggesting that other factors need
to be considered. However, this study highlighted the significant increases in
time required to fabricate more value-added cuts and to breakdown heavier
carcases. Furthermore, this study demonstrated the changes to the saleable meat
yield as the degree of fabrication increased, such that the average product
prices increased ($20.64/kg for mid value added and $28.72/kg for extreme value
added) compared to traditional retail cuts ($15/kg) to offset the increased
labour of fabricating value-added cuts.
PMID- 28514709
TI - Protein adsorption on implant metals with various deformed surfaces.
AB - The adsorption of proteins has great influence on the biocompatibility,
lubrication and corrosion properties of implantable metals. The subsurface
microstructure of metals can be easily changed during the manufacturing or
service processes and it is easily ignored. The same chemical composition but
with various surface microstructures can result in very different adsorption
behaviour. In this study, mechanical polishing, electrochemical polishing and
shot peening methods were used to generate different gradient deformed surfaces
for CoCrMo alloys. The increase of the residual compressive stress and the
decrease of grains to a nano-size on the deformed subsurface can effectively
enhance the activity of metal atoms and improve the element diffusion, that is
helpful in forming a more compact passive film. This can increase the contents of
oxides on the surface, and then enhance the electrostatic force and increase the
surface's positive charge density as well as adsorption sites. All of the above
facilitated the adsorption of the negatively charged albumin onto the alloy
surface.
PMID- 28514710
TI - Multi-layered nanogels with MMP-sheddable PEG masks: Preparation and promotion of
tumor cell uptake by controlling surface characteristics.
AB - We describe a facile and effective poly(ethylene glycol) (PEG) coating method
that has not been used previously for decoration of nanogels. Layer-by-layer
(LbL) assembly was the technique of choice to introduce PEG onto the surface of
multi-layered nanogels (MLNGs). Pegylated MLNGs were prepared simply by
sequentially dispersing nanogels in solutions of cationic polymer, anionic
polymer, and modified PEGs, and each coating step was validated by measuring
changes in size and surface charge. Particularly, a peptide linker that is
cleavable by matrix metalloproteinase-2 (MMP-2) in the tumor microenvironment was
introduced between PEG layer and nanogels because it is known that PEG reduces
the uptake of nanoparticles in tumor cells due to its high mobility. In vitro
cell studies demonstrated that MLNGs with MMP-cleavable PEGs enhanced the
particle uptake up to 3 times in tumor cells due to unmasking of PEG brushes as
compared to pegylated MLNGs without MMP-sensitive peptide linkers.
PMID- 28514711
TI - Self-assembly of DNA-porphyrin hybrid molecules for the creation of antimicrobial
nanonetwork.
AB - DNA derived well-controlled arrangement of porphyrins has emerged as promising
hybrid nanostructures. Exceptional biocompatibility and DNA-directed surface
addressability coupled with rich symmetry features of the porphyrin have made
these hybrid nanostructures attractive candidates for potential biomedical and
biotechnological applications. However, the noteworthy photophysical properties
of porphyrin and related molecules when present in DNA based nanostructures are
yet to be explored fully and should be a matter of intense research that may
unearth a plethora of interesting applications of these nanostructures. Herein,
we demonstrate the construction of novel self-assembled DNA-porphyrin hybrid
nanonetworks that utilize the porphyrin core for antibacterial applications.
Porphyrin derivative with four pendant NH2 groups was synthesized and conjugated
with the 5'-PO4 of ss-DNA by solution phase phosphoramidation coupling reaction.
The conjugation was followed by DNA hybridization mediated self-assembly to form
DNA-porphyrin hybrid nanonetwork. The enhanced antimicrobial property of the
nanonetwork was envisioned following light irradiation at relevant wavelength. In
line with this, comparative antimicrobial activities against gram-negative
(Escherichia coli BL-21) and gram-positive bacteria (Staphylococcus aureus) have
been studied. Interestingly, DNA-porphyrin nanonetwork afforded highly efficient
and coherent photoinduced reactive oxygen species (ROS) generation to display
antimicrobial activity against Staphylococcus aureus. The escalated and coherent
ROS generation from the nanonetworks was attributed to the ordered placement of
the porphyrins that inhibits self-quenching. Our work points out to a good
alternative for antibiotic free strategies for preservation of biological
materials and other applications.
PMID- 28514712
TI - Nitrogen doped carbon dots derived from Sargassum fluitans as fluorophore for DNA
detection.
AB - This work focused on the use of waste seaweed Sargassum fluitans (S. fluitans) as
carbon source precursor to prepare nitrogen doped carbon dots (NCDs) by
hydrothermal method. High resolution transmission electron microscopic (HR-TEM)
studies revealed that the synthesized water soluble NCDs are in the size range of
2-8nm and exhibits excellent fluorescent properties with a quantum yield of
18.2%. Elemental nitrogen in NCDs was evidenced by X-ray photoelectron
spectroscopy (XPS) and Fourier transformed infrared spectrum (FT-IR). The
phytochemical analysis of S. fluitans using 1H NMR and 13C NMR revealed the
presence of few amino acids which act as nitrogen source in the preparation of
NCDs. Application of NCDs as fluorophore for double stranded DNA, single stranded
DNA and RNA detection was highlighted in this study. Excellent fluorescent
tagging abilities of NCDs with the biological nucleic acids were evidenced using
gel electrophoresis. Significant increase in fluorescence was observed upon
tagging of NCDs with nucleic acids and this particular phenomenon helps better in
visualizing the nucleic acids. All three nucleic acids i.e. double stranded DNA,
single stranded DNA and RNA showed similar phenomenon upon tagging with NCDs.
Thus synthesized NCDs may be used as an alternate fluorophore for commercial
toxic organic staining agents to visualize nucleic acids.
PMID- 28514713
TI - Pattern recognition receptors and coordinated cellular pathways involved in
tuberculosis immunopathogenesis: Emerging concepts and perspectives.
AB - Pattern Recognition Receptors (PRRs) play a central role in the recognition of
numerous pathogens, including Mycobacterium tuberculosis, resulting in activation
of innate and adaptive immune responses. Besides Toll Like Receptors, C-type
Lectin Receptors and Nod Like Receptors are now being recognized for their
involvement in inducing immune response against M. tuberculosis infection.
Although, a functional redundancy of the PRRs has also been reported in many
studies, emerging evidences support the notion that a cooperative and coordinated
response generated by these receptors is critical to sustain the full immune
control of M. tuberculosis infection. Many of the PRRs are now found to be
involved in various cellular host defenses, such as inflammasome activation,
phagosome biogenesis, endosomal trafficking, and antigen processing pathways that
are all very critical for an effective immune response against M. tuberculosis.
In support, polymorphism in several of these receptors has also been found
associated with increased susceptibility to tuberculosis in humans. Nonetheless,
increasing evidences also show that in order to enhance its intracellular
survival, M. tuberculosis has also evolved multiple strategies to subvert and
reprogram PPR-mediated immune responses. In light of these findings, this review
analyzes the interaction of bacterial and host factors at the intersections of
PRR signaling pathways that could provide integrative insights for the
development of better vaccines and therapeutics for tuberculosis.
PMID- 28514714
TI - Calcitonin protects chondrocytes from lipopolysaccharide-induced apoptosis and
inflammatory response through MAPK/Wnt/NF-kappaB pathways.
AB - Calcitonin (CT) is an anti-absorbent, which has long been used for treatment of
osteoporosis. However, little information is available about the effects of CT on
osteoarthritis (OA). This study was mainly aimed to explore the effects of CT on
the treatment of OA, as well as the underlying mechanisms. Chondrocytes were
isolated from immature mice and then were incubated with lipopolysaccharide
(LPS), CT, small interfering (si) RNA against bone morphogenetic protein (BMP)-2,
and/or the inhibitors of MAPK/Wnt/NF-kappaB pathway. Thereafter, cell viability,
apoptosis, nitric oxide (NO) and inflammatory factors productions, and expression
levels of cartilage synthesis protein key factors, cartilage-derived
morphogenetic protein (CDMP) 1, SRY (sex-determining region Y)-box 9 protein
(SOX9), and MAPK/Wnt/NF-kappaB pathways key factors were determined. CT
significantly reversed LPS-induced cell viability decrease, apoptosis increase,
the inflammatory factors and NO secretion, the abnormally expression of cartilage
synthesis proteins and the activation of MAPK/Wnt/NF-kappaB pathways (P<0.05). In
addition, we observed that administration of the inhibitors of MAPK/Wnt/NF-kappaB
pathways statistically further increased the levels of CDMP1 and SOX9 (P<0.05).
Suppression of BMP-2 decreased the levels of CDMP1 and SOX9 and activated
MAPK/Wnt/NF-kappaB pathways, and could partially abolish CT-modulated the
expression changes in CDMP1 and SOX9, and MAPK/Wnt/NF-kappaB pathways key factors
(P<0.05). The results showed that CT protects chondrocytes from LPS-induced
apoptosis and inflammatory response by regulating BMP-2 and thus blocking
MAPK/Wnt/NF-kappaB pathways.
PMID- 28514715
TI - Impact of physician education and availability of parameters regarding esophageal
pressure and transpulmonary pressure on clinical decisions involving ventilator
management.
AB - PURPOSE: This study investigated the effects of physician education and the
availability of Peso and PL data on physicians' decisions regarding ventilator
management during specific simulated clinical conditions. MATERIALS AND METHODS:
The study was a prospective, before-after study using a case scenario-based
questionnaire and a case simulator device comprising an Avea ventilator and an
artificial lung and esophagus, which was connected to a Series 1101 Electronic
Breathing Simulator. The 99 physicians participating in the study were provided
with five simulated cases with on-time ventilator graphics without Peso and PL
and completed a questionnaire on decisions they would make regarding ventilator
management of the cases. Then, after receiving instruction on Peso and PL, they
were given the same cases along with ventilator graphics that included Peso and
PL. RESULTS: After receiving instruction and data on Peso and PL, statistically
significant numbers of physicians changed their answers regarding ventilator
management decisions in all five cases. CONCLUSIONS: Providing education and data
for Peso and PL had a significant effect on physician decisions regarding
ventilator management in simulated cases. The use of case scenario-based
education with simulator devices for physicians may hasten worldwide
understanding and clinical application of Peso and PL.
PMID- 28514716
TI - C-reactive protein, procalcitonin and interleukin-6 kinetics in pediatric
postoperative patients.
PMID- 28514717
TI - Quantification of active ingredients in semi-solid pharmaceutical formulations by
near infrared spectroscopy.
AB - Near infrared (NIR) spectroscopy is increasingly gaining significance in the
pharmaceutical industry for quality and in-process control. However, the
potential of this method for quantitative quality control in pharmacies has long
been neglected and little data is available on its application in analysis of
creams and ointments. This study evaluated the applicability of NIR spectrometer
with limited wavelength range (1000-1900nm) for quantitative quality control of
six different dermatological semi-solid pharmaceutical preparations. Each
contained a frequently used active ingredient in a common concentration either in
a water-free lipid base or in an aqueous cream matrix. Based on direct NIR
transflectance measurements through standardized glass beakers and partial least
squares (PLS) multivariate calibration, quantitative models were generated
comparing several data pre-processing methods Whereas difficulties were observed
for mixtures containing 2% (w/w) metronidazole or 4% (w/w) erythromycin, content
determination was possible with sufficient accuracy for salicylic acid (5 %
(w/w)) and urea (10% (w/w)) in hydrophilic as well as in lipophilic formulations
meeting the limit of a maximum deviation of+/-5% (relative) from the reference
values. Exemplarily, one of the methods was successfully validated according to
the EMA Guideline, determining several figures of merit such as specificity,
linearity, accuracy, precision and robustness.
PMID- 28514718
TI - Exploring the neuroprotective effects of ginkgolides injection in a rodent model
of cerebral ischemia-reperfusion injury by GC-MS based metabolomic profiling.
AB - Cerebral ischemia-reperfusion (I/R) injury usually contributes to mortality and
disability after ischemic stroke. Ginkgolides injection (GIn), a standard
preparation composed of ginkgo diterpene lactones extract, is clinically used for
neuroprotective treatment on reconvalescents of cerebral infarction. However, the
understanding about its therapeutic mechanism is still lacking. In this study, a
gas chromatography-mass spectrometry (GC-MS) based metabolomic approach coupled
with multivariate data analysis (MVDA) was applied to explore the neuroprotective
effects of GIn in a rodent model of focal ischemic stroke induced by transient
middle cerebral artery occlusion (tMCAO). Metabolomic profiling revealed a series
of metabolic perturbations that underlie the cerebral I/R pathological events.
GIn can reverse the I/R induced brain metabolic deviations by modulating multiple
metabolic pathways, such as glycolysis, Krebs cycle, pentose phosphate pathway
(PPP), gamma-aminobutyrate (GABA) shunt and lipid metabolism. Moreover, the main
bioactive components of GIn were distributed to brain tissue much more easily in
tMCAO rats than in normal rats after an intravenous administration, suggesting
that the increased cerebral exposure to ginkgolides in I/R pathological condition
potentially facilitated the neuroprotective effects of GIn by directly targeting
at brain. The present study provided valuable information for our understanding
about metabolic changes of cerebral I/R injury and clinical application of GIn.
PMID- 28514719
TI - Multiway analysis methods applied to the fluorescence excitation-emission dataset
for the simultaneous quantification of valsartan and amlodipine in tablets.
AB - In this study, excitation-emission matrix datasets, which have strong overlapping
bands, were processed by using four different chemometric calibration algorithms
consisting of parallel factor analysis, Tucker3, three-way partial least squares
and unfolded partial least squares for the simultaneous quantitative estimation
of valsartan and amlodipine besylate in tablets. In analyses, preliminary
separation step was not used before the application of parallel factor analysis
Tucker3, three-way partial least squares and unfolded partial least squares
approaches for the analysis of the related drug substances in samples. Three-way
excitation-emission matrix data array was obtained by concatenating excitation
emission matrices of the calibration set, validation set, and commercial tablet
samples. The excitation-emission matrix data array was used to get parallel
factor analysis, Tucker3, three-way partial least squares and unfolded partial
least squares calibrations and to predict the amounts of valsartan and amlodipine
besylate in samples. For all the methods, calibration and prediction of valsartan
and amlodipine besylate were performed in the working concentration ranges of
0.25-4.50MUg/mL. The validity and the performance of all the proposed methods
were checked by using the validation parameters. From the analysis results, it
was concluded that the described two-way and three-way algorithmic methods were
very useful for the simultaneous quantitative resolution and routine analysis of
the related drug substances in marketed samples.
PMID- 28514720
TI - New application for haplotype-specific extraction: Separation of mitochondrial
DNA mixtures.
AB - A particularly challenging aspect of forensic casework is the accurate
interpretation of samples that contain DNA from more than one contributor, since
DNA analysis of specific identification markers often results in ambiguous mixed
profiles. Physically separating the various haploid components of a diploid or
polyploid DNA sample or of a specimen containing DNA from multiple individuals
can resolve this problem. We adapted and combined previously developed methods of
haplotype-specific extraction (HSE) to separate and analyze mitochondrial DNA
(mtDNA) in samples containing DNA from two individuals. After optimizing
conditions and probes, we performed HSE to separate mitochondrial DNA mixtures,
which manifest as mixed nucleotide calls at single base positions. We were able
to subsequently identify the DNA of the two individuals by sequencing. Based on
our findings from this proof-of-concept experiment, this novel assay will be
useful for distinguishing among the mtDNA of individuals in mixed DNA samples.
PMID- 28514721
TI - Impact of GH administration on athletic performance in healthy young adults: A
systematic review and meta-analysis of placebo-controlled trials.
AB - OBJECTIVE: Illicit use of growth hormone (GH) as a performance-enhancing drug
among athletes is prevalent, although the evidence of such effects in healthy,
young subjects is sparse. We therefore performed a meta-analysis of published
studies on the effect of GH administration on body composition, substrate
metabolism, and athletic performance in healthy, young subjects. DESIGN: The
English-language based databases PubMed, EMBASE, and Cochrane Central Register of
Controlled Trials were searched, and eligible articles were reviewed in
accordance with the PRISMA guidelines. Fifty-four potentially relevant articles
were retrieved of which 11 were included in this analysis comprising 254
subjects. RESULTS: Administration of GH significantly increased lean body mass
(p<0.01) and decreased fat mass (p<0.01). In addition, GH increased the
exercising levels of glycerol (p=0.01) and free fatty acids (p<0.01), but did not
alter the respiratory quotient during exercise (p=0.30). GH significantly
increased anaerobic exercise capacity (p<0.01) in the only study which
investigated this, but did not over weeks to months improve muscle strength
(p=0.36) or maximum oxygen uptake (p=0.89). CONCLUSION: GH administration elicits
significant changes in body composition, but does not increase either muscle
strength or aerobic exercise capacity in healthy, young subjects.
PMID- 28514722
TI - The interventional effect of new drugs combined with the Stupp protocol on
glioblastoma: A network meta-analysis.
AB - OBJECTIVE: New therapeutic agents in combination with the standard Stupp protocol
(a protocol about the temozolomide combined with radiotherapy treatment with
glioblastoma was research by Stupp R in 2005) were assessed to evaluate whether
they were superior to the Stupp protocol alone, to determine the optimum
treatment regimen for patients with newly diagnosed glioblastoma. PATIENTS AND
METHODS: We implemented a search strategy to identify studies in the following
databases: PubMed, Cochrane Library, EMBASE, CNKI, CBM, Wanfang, and VIP, and
assessed the quality of extracted data from the trials included. Statistical
software was used to perform network meta-analysis. RESULTS: The use of novel
therapeutic agents in combination with the Stupp protocol were all shown to be
superior than the Stupp protocol alone for the treatment of newly diagnosed
glioblastoma, ranked as follows: cilengitide 2000mg/5/week, bevacizumab in
combination with irinotecan, nimotuzumab, bevacizumab, cilengitide 2000mg/2/week,
cytokine-induced killer cell immunotherapy, and the Stupp protocol. In terms of
serious adverse effects, the intervention group showed a 29% increase in the
incidence of adverse events compared with the control group (patients treated
only with Stupp protocol) with a statistically significant difference (RR=1.29;
95%CI 1.17-1.43; P<0.001). The most common adverse events were thrombocytopenia,
lymphopenia, neutropenia, pneumonia, nausea, and vomiting, none of which were
significantly different between the groups except for neutropenia, pneumonia, and
embolism. CONCLUSIONS: All intervention drugs evaluated in our study were
superior to the Stupp protocol alone when used in combination with it. However,
we could not conclusively confirm whether cilengitide 2000mg/5/week was the
optimum regime, as only one trial using this protocol was included in our study.
PMID- 28514723
TI - Genomic profiling of pelvic genital type leiomyosarcoma in a woman with a
germline CHEK2:c.1100delC mutation and a concomitant diagnosis of metastatic
invasive ductal breast carcinoma.
AB - We describe a woman with the known pathogenic germline variant CHEK2:c.1100delC
and synchronous diagnoses of both pelvic genital type leiomyosarcoma (LMS) and
metastatic invasive ductal breast carcinoma. CHEK2 (checkpoint kinase 2) is a
tumor-suppressor gene encoding a serine/threonine-protein kinase (CHEK2) involved
in double-strand DNA break repair and cell cycle arrest. The CHEK2:c.1100delC
variant is a moderate penetrance allele resulting in an approximately twofold
increase in breast cancer risk. Whole-genome and whole-transcriptome sequencing
were performed on the leiomyosarcoma and matched blood-derived DNA. Despite the
presence of several genomic hits within the double-strand DNA damage pathway
(CHEK2 germline variant and multiple RAD51B somatic structural variants), tumor
profiling did not show an obvious DNA repair deficiency signature. However, even
though the LMS displayed clear malignant features, its genomic profiling revealed
several characteristics classically associated with leiomyomas including a
translocation, t(12;14), with one breakpoint disrupting RAD51B and the other
breakpoint upstream of HMGA2 with very high expression of HMGA2 and PLAG1 This is
the first report of LMS genomic profiling in a patient with the germline
CHEK2:c.1100delC variant and an additional diagnosis of metastatic invasive
ductal breast carcinoma. We also describe a possible mechanistic relationship
between leiomyoma and LMS based on genomic and transcriptome data. Our findings
suggest that RAD51B translocation and HMGA2 overexpression may play an important
role in LMS oncogenesis.
PMID- 28514730
TI - Circulating microRNAs as novel biomarkers of ALK-positive nonsmall cell lung
cancer and predictors of response to crizotinib therapy.
AB - Circulating microRNAs are potential diagnostic and predictive biomarkers, but
have not been investigated for patients with anaplastic lymphoma kinase (ALK)
positive lung cancer. In this exploratory study, we sought to identify potential
plasma biomarkers for ALK-positive non-small cell lung cancer (NSCLC). A microRNA
microarray was used to select ALK-related microRNAs in ALK-positive NSCLC (n =
3), ALK-negative NSCLC (n = 3), and healthy subjects (n = 3). Plasma levels of 21
microRNAs were differentially expressed for ALK-positive and ALK-negative NSCLC,
including 14 down-regulated and 7 up-regulated microRNAs. We also identified 5s
rRNA as the most stable endogenous control gene using geNorm and NormFinder
algorithms. Candidate microRNAs in plasma from ALK-positive (n = 41) and ALK
negative NSCLC patients (n = 32) were quantified using real-time reverse
transcriptase quantitative polymerase chain reaction. The expression levels of
miR-28-5p, miR-362-5p, and miR-660-5p were all down-regulated in ALK-positive
NSCLC, compared with ALK-negative NSCLC. The areas under the receiver operating
characteristic curves of miR-28-5p, miR-362-5p, miR-660-5p, and 3-microRNAs panel
were 0.873, 0.673, 0.760, and 0.876, respectively. The positive predictive values
of miR-28-5p, miR-362-5p, and miR-660-5p were 96.43%, 80.77%, and 83.87%,
respectively. Increased plasma levels of miR-660-5p after crizotinib treatment
predicted good tumor response (p = 0.012). The pre-crizotinib levels of miR-362
5p were significantly associated with progression-free survival (p = 0.015).
Thus, in this preliminary investigation, we identified a potential panel of 3
microRNAs for distinguishing between patients with ALK-positive and ALK-negative
NSCLC. We also identified miR-660-5p and miR-362-5p as potential predictors for
response to crizotinib treatment.
PMID- 28514733
TI - Role of intravoxel incoherent motion MR imaging in preoperative assessing HER2
status of gastric cancers.
AB - PURPOSE: To explore the role of intravoxel incoherent motion (IVIM) magnetic
resonance (MR) imaging in evaluating human epidermal growth factor receptor 2
(HER2) status of gastric cancers preoperatively. RESULTS: The apparent diffusion
coefficient (ADC) and pure diffusion coefficient (D) values correlated positively
with HER2 scores of gastric cancers significantly (r = 0.276, P = 0.048; r =
0.481, P < 0.001, respectively). The ADC and D values of HER2 positive gastric
cancers were significantly higher than those of HER2 negative tumors (P = 0.033,
0.007, respectively). With a cut-off value of 1.321 and 1.123 * 10-3 mm2/sec, the
ADC and D values could distinguish HER2 positive gastric cancers from HER2
negative ones with an area under the curve of 0.733 and 0.762, respectively (P =
0.023, 0.011, respectively). MATERIALS AND METHODS: Fifty-three patients with
gastric cancers underwent IVIM MR imaging preoperatively. The values of ADC, D,
pseudo diffusion coefficient (D*) and perfusion related fraction (f) of the
lesions were obtained. Partial correlation test including tumor volume was
performed to analyze correlations between IVIM values and HER2 scores excluding
the impact of tumor size. IVIM parameters of gastric cancers with different HER2
status were compared using independent samples t test. Diagnostic performance of
IVIM parameters in distinguishing HER2 positive gastric cancers from negative
ones was tested with receiver operating characteristic analysis. CONCLUSIONS: We
confirmed the feasibility of IVIM MR imaging in preoperative assessment of HER2
status of gastric cancers, which might make up the shortfall of biopsy and
facilitate personalized treatment for patients with gastric cancers.
PMID- 28514734
TI - Inflammatory microRNA-194 and -515 attenuate the biosynthesis of chondroitin
sulfate during human intervertebral disc degeneration.
AB - Intervertebral disc degeneration (IDD) is characterized by dehydration and loss
of extracellular matrixes in the nucleus pulposus region. Chondroitin sulfate has
been found to be the water-binding molecule that played a key role in IDD.
Although investigators have reported that inflammatory cytokines are involved in
the reduction of chondroitin sulfate in IDD, but the underlying mechanism is
unrevealed. Since chondroitin sulfate synthesis is controlled by chondroitin
sulfate glycosyltransferases CHSY-1/2/3 and CSGALNACT-1/2, their functional role
and regulatory mechanism in IDD is not fully studied. Here, we set out to
investigate the function and regulatory roles of these factors during IDD
development. We found that among these chondroitin sulfate glycosyltransferases,
CHSY-1/2/3 are significantly down-regulated in severe IDD samples than mild IDD
samples. In vitro experiments revealed that Interleukin-1beta and Tumor Necrosis
Factor-alpha stimulation led to significant reduction of CHSY-1/2/3 at protein
level than mRNA level in NP cells, indicating a post-transcriptional regulatory
mechanisms are involved. By computational prediction and analysis, we found that
inflammatory cytokines stimulated microRNA-194 and -515 target CHSY-1/2/3 mRNA
and significantly interrupt their translation and downstream chondroitin sulfate
deposition. Inhibition of microRNA-194 and -515 however, significantly rescued
CHSY-1/2/3 expressions and chondroitin sulfate deposition. These findings
together demonstrated a vital role of inflammatory stimulated microRNAs in
promoting intervertebral disc degeneration by interrupt chondroitin sulfate
synthesis, which may provide new insights into the mechanism and therapeutic
approaches in IDD.
PMID- 28514744
TI - Characterization of mouse serum exosomal small RNA content: The origins and their
roles in modulating inflammatory response.
AB - In the last decade, although studies on exosomal microRNAs (miRNAs) derived from
serum and other body fluids have increased dramatically; the contents and
biological significance of serum exosomes under normal conditions remain unclear.
In the present study, we profiled the small RNA content of mouse serum exosomes
(mSEs) using small RNAseq and found that fragments of transfer RNAs (tRNAs) and
miRNAs were the two predominant exosomal RNA species, accounting for
approximately 60% and 10% of mapped reads, respectively. Moreover, 466 known and
5 novel miRNAs were identified from two independent experiments, among which the
five most abundant miRNAs (miR-486a-5p, miR-22-3p, miR-16-5p, miR-10b-5p and miR
27b-3p) accounted for approximately 60% of all the aligned miRNA sequences. As
inferred from the identities of the well known cell- or tissue-specific miRNAs,
mSEs were primarily released by RBCs, liver and intestinal cells. Bioinformatics
analysis revealed over half of the top 20 miRNAs by abundance were involved in
inflammatory responses and further in vitro experiments demonstrated that mSEs
potently primed macrophages towards the M2 phenotype. To the best of our
knowledge, this is the first study to profile small RNAs from mSEs. In addition
to providing a reference for future biomarker studies and extrapolating their
origins, our data also suggest the roles of mSEs in maintaining internal
homeostasis under normal conditions.
PMID- 28514745
TI - Combating acquired resistance to trastuzumab by an anti-ErbB2 fully human
antibody.
AB - Trastuzumab resistance is a common problem that impedes the effectiveness of
trastuzumab in ErbB2-amplified cancers. About 70% of ErbB2-amplified breast
cancers do not respond to trastuzumab (de novo resistance), and the majority of
the trastuzumab-responsive cancers progress within 1 year (acquired resistance).
Different mechanisms exist between de novo and acquired resistance. Innate
resistance mechanisms are mainly independent of ErbB2 receptor activity, and
acquired resistance involves with alterations depending on ErbB2 activity. We
previously reported H2-18, an ErbB2 domain I-specific antibody, which could
circumvent de novo resistance to trastuzumab. Here, we modeled the development of
acquired resistance by treating human gastric cancer cell line NCI-N87 with
trastuzumab to obtain the trastuzumab-resistant subline, NCI-N87-TraRT. Next, we
investigated the antitumor efficacy of H2-18 in NCI-N87-TraRT cell line. H2-18
exhibited a significantly greater antitumor activity in NCI-N87-TraRT tumor
bearing nude mice than pertuzumab and trastuzumab, either alone or in
combination. The unique ability of H2-18 to overcome acquired resistance may be
attributable to its potent programmed cell death-inducing activity, which was
probably mediated by RIP1-ROS-JNK-c-Jun pathway. In conclusion, H2-18 may have
the potential as an effective agent to circumvent acquired resistance to
trastuzumab in ErbB2-overexpressing cancers.
PMID- 28514746
TI - Diagnostic and prognostic values of endothelial-cell-specific molecule-1 with
malignant pleural effusions in patients with non-small cell lung cancer.
AB - Over-expressed endothelial-cell-specific molecule-1 (ESM-1) in tumor vascular
endothelium contributes to tumor angiogenesis, metastasis, and poor prognosis.
However, the content of ESM-1 in pleural effusion is unclear. A retrospective
study was carried out to investigate the diagnostic and prognostic values of ESM
1 with malignant pleural effusions in patients with non-small cell lung cancer
(NSCLC). ESM-1 levels in malignant pleural effusion (MPE) from 70 patients with
NSCLC and 50 cases of benign pleural effusion (BPE) were measured using enzyme
linked immunosorbent assay. Receiver operating characteristic (ROC) curve was
calculated to assess the diagnostic value of ESM-1. Survival curves were
performed by Kaplan-Meier method and survival characteristics were compared by
log-rank test. Univariable and multivariate Cox proportional hazards model were
carried out to analysis the significance of different prognostic factors for
overall survival (OS). ESM-1 levels were significantly higher in MPE than those
in BPE (p < 0.001). By ROC curve analysis, with a cutoff level of 19.58 ng/ml,
the accuracy, sensitivity, and specificity for ESM-1 diagnosis MPE were 82.5%,
81.4%, and 84.0%, respectively. Moreover, NSCLC patients with pleural fluid ESM-1
levels below 19.58 ng/ml had significant longer OS than those patients with
higher levels (22.09 months vs. 11.49 months, p = 0.003). Multivariate survival
analysis showed that high MPE ESM-1 level was an independent prognostic factor
(HR, 1.007; p = 0.039) for the OS of NSCLC patients. This study showed that ESM-1
level in pleural effusion could be a potential diagnostic and prognostic marker
in NSCLC patients with MPE.
PMID- 28514747
TI - Diagnostic value of using 18F-FDG PET and PET/CT in immunocompetent patients with
primary central nervous system lymphoma: A systematic review and meta-analysis.
AB - BACKGROUND: 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)
and PET/CT have become two of the most powerful tools for malignant lymphoma
exploration, but their diagnostic role in primary central nervous system lymphoma
(PCNSL) is still disputed. The purpose of our study is to identify the usefulness
of 18F-FDG PET and PET/CT for detecting PCNSL. RESULTS: A total of 129 patients,
obtained from eight eligible studies, were included for this systematic review
and meta-analysis. The performance of 18F-FDG PET and PET/CT for diagnosing PCNSL
were as follows: the pooled sensitivity was 0.88 (95% CI: 0.80-0.94), specificity
was 0.86 (95% CI: 0.73-0.94), positive likelihood ratio (PLR) was 3.99 (95% CI:
2.31-6.90), negative likelihood ratio (NLR) was 0.11 (95% CI: 0.04-0.32), and
diagnostic odds ratio (DOR) was 33.40 (95% CI: 10.40-107.3). In addition, the
area under the curve (AUC) and Q index were 0.9192 and 0.8525, respectively.
MATERIALS AND METHODS: PubMed/MEDLINE, Embase and Cochrane Library were
systematically searched for potential publications (last updated on July 16th,
2016). Reference lists of included articles were also checked. Original articles
that reported data on patients who were suspected of having PCNSL were considered
suitable for inclusion. The sensitivities and specificities of 18F-FDG PET and
PET/CT in each study were evaluated. The Stata software and Meta-Disc software
were employed in the process of data analysis. CONCLUSIONS: 18F-FDG PET and
PET/CT showed considerable accuracy in identifying PCNSL in immunocompetent
patients and could be a valuable radiological diagnostic tool for PCNSL.
PMID- 28514737
TI - Integration of phytochemicals and phytotherapy into cancer precision medicine.
AB - Concepts of individualized therapy in the 1970s and 1980s attempted to develop
predictive in vitro tests for individual drug responsiveness without reaching
clinical routine. Precision medicine attempts to device novel individual cancer
therapy strategies. Using bioinformatics, relevant knowledge is extracted from
huge data amounts. However, tumor heterogeneity challenges chemotherapy due to
genetically and phenotypically different cell subpopulations, which may lead to
refractory tumors. Natural products always served as vital resources for cancer
therapy (e.g., Vinca alkaloids, camptothecin, paclitaxel, etc.) and are also
sources for novel drugs. Targeted drugs developed to specifically address tumor
related proteins represent the basis of precision medicine. Natural products from
plants represent excellent resource for targeted therapies. Phytochemicals and
herbal mixtures act multi-specifically, i.e. they attack multiple targets at the
same time. Network pharmacology facilitates the identification of the complexity
of pharmacogenomic networks and new signaling networks that are distorted in
tumors. In the present review, we give a conceptual overview, how the problem of
drug resistance may be approached by integrating phytochemicals and phytotherapy
into academic western medicine. Modern technology platforms (e.g. "-omics"
technologies, DNA/RNA sequencing, and network pharmacology) can be applied for
diverse treatment modalities such as cytotoxic and targeted chemotherapy as well
as phytochemicals and phytotherapy. Thereby, these technologies represent an
integrative momentum to merge the best of two worlds: clinical oncology and
traditional medicine. In conclusion, the integration of phytochemicals and
phytotherapy into cancer precision medicine represents a valuable asset to
chemically synthesized chemicals and therapeutic antibodies.
PMID- 28514748
TI - A transcriptional complex composed of ER(alpha), GATA3, FOXA1 and ELL3 regulates
IL-20 expression in breast cancer cells.
AB - Interleukin-20 (IL-20) is a member of the IL-10 family. IL-20 expression is
regulated by a transcription elongation factor, Ell3, in estrogen receptor
positive (ER(+)) breast cancer cells. In this study, we demonstrated that
ER(alpha), GATA3 and FOXA1 form a transcriptional complex with Ell3 to regulate
IL-20 expression in ER(+) breast cancer cells. We also determined that GATA3 and
FOXA1 share a binding site with ER(alpha) in the interleukin-20 promoter.
Furthermore, we found that FOXA1 represses IL-20 expression, whereas GATA3 and
ER(alpha) activate it. In addition, we demonstrated that Ell3 associates with
ER(alpha) to increase its binding affinity to the IL-20 promoter, which may
prevent FOXA1 binding to the same region of this promoter. Our results expand
upon the current understanding of the regulatory mechanism of IL-20 in cancer.
PMID- 28514749
TI - A variant in SIRT2 gene 3'-UTR is associated with susceptibility to colorectal
cancer.
AB - SIRT2 is a member of sirtuin family and is associated with cell growth in various
cancers. In this study, we searched for variants in functional region of SIRT2
gene and identify rs2015 and rs2241703 in the 3'UTR with minor allele frequency
>0.05 in Chinese Han Beijing population from 1000 Genomes Project. We then
genotyped these two variants in 842 colorectal cancer (CRC) patients and 1,718
healthy controls using Taqman genotyping assay. Association between variants and
risk of CRC is calculated using logistic regression adjusted for sex and age. We
found that rs2015C was significantly associated with increased risk of CRC.
Compared with CC genotype carriers, CA genotype and AA genotype carriers were
associated with CRC susceptibility with OR being 0.79 (95% CI: 0.65-0.96, P =
0.019) and 0.73 (95% CI: 0.58-0.92, P = 0.009), respectively. When stratified by
sex and age, significant associations were observed only in males (OR = 0.82, 95%
CI: 0.71-0.96, P = 0.010) for rs2015, but not females (OR = 0.90, 95% CI: 0.73
1.10, P = 0.287). It is suggested that the sequence including rs2015C allele lies
within a binding site for the full seed region of hsa-miR-376a-5p. Through a
systematic interrogate of variants in the functional region of SIRT2 gene, we
identified rs2015 was significantly associated with CRC susceptibility, providing
new insights into the carcinogenesis of CRC.
PMID- 28514750
TI - Epigenome-wide association study in hepatocellular carcinoma: Identification of
stochastic epigenetic mutations through an innovative statistical approach.
AB - Hepatocellular carcinoma (HCC) results from accumulation of both genetic and
epigenetic alterations. We investigated the genome-wide DNA methylation profile
in 69 pairs of HCC and adjacent non-cancerous liver tissues using the Infinium
HumanMethylation 450K BeadChip array. An innovative analytical approach has been
adopted to identify Stochastic Epigenetic Mutations (SEMs) in HCC.HCC and
peritumoral tissues showed a different epigenetic profile, mainly characterized
by loss of DNA methylation in HCC. Total number of SEMs was significantly higher
in HCC tumor (median: 77,370) than in peritumoral (median: 5,656) tissues and
correlated with tumor grade. A significant positive association emerged between
SEMs measured in peritumoral tissue and hepatitis B and/or C virus infection
status. A restricted number of SEMs resulted to be shared by more than 90% of HCC
tumor samples and never present in peritumoral tissue. This analysis allowed the
identification of four epigenetically regulated candidate genes (AJAP1, ADARB2,
PTPRN2, SDK1), potentially involved in the pathogenesis of HCC.In conclusion, HCC
showed a methylation profile completely deregulated and very far from adjacent
non-cancerous liver tissues. The SEM analysis provided valuable clues for further
investigations in understanding the process of tumorigenesis in HCC.
PMID- 28514751
TI - Large-scale clinical validation of biomarkers for pancreatic cancer using a mass
spectrometry-based proteomics approach.
AB - We performed an integrated analysis of proteomic and transcriptomic datasets to
develop potential diagnostic markers for early pancreatic cancer. In the
discovery phase, a multiple reaction monitoring assay of 90 proteins identified
by either gene expression analysis or global serum proteome profiling was
established and applied to 182 clinical specimens. Nine proteins (P < 0.05) were
selected for the independent validation phase and quantified using stable isotope
dilution-multiple reaction monitoring-mass spectrometry in 456 specimens. Of
these proteins, four proteins (apolipoprotein A-IV, apolipoprotein CIII, insulin
like growth factor binding protein 2 and tissue inhibitor of metalloproteinase 1)
were significantly altered in pancreatic cancer in both the discovery and
validation phase (P < 0.01). Moreover, a panel including carbohydrate antigen 19
9, apolipoprotein A-IV and tissue inhibitor of metalloproteinase 1 showed better
performance for distinguishing early pancreatic cancer from pancreatitis (Area
under the curve = 0.934, 86% sensitivity at fixed 90% specificity) than
carbohydrate antigen 19-9 alone (71% sensitivity).Overall, we present the panel
of robust biomarkers for early pancreatic cancer diagnosis through bioinformatics
analysis that combined transcriptomic and proteomic data as well as rigorous
validation on a large number of independent clinical samples.
PMID- 28514753
TI - Impact of age on the diagnostic performances and cut-offs of APRI and FIB-4 for
significant fibrosis and cirrhosis in chronic hepatitis B.
AB - AIMS: Assessing the diagnostic performances of APRI and FIB-4 using age as a
categorical marker. METHODS: 822 chronic hepatitis B (CHB) patients were
included. Using METAVIR scoring system as a reference, the performances of APRI
and FIB-4 were compared between patients aged>=30 and patients aged<30 years.
RESULTS: The APRI AUROC in patients aged<30 years was lower than that in patients
aged>=30 years for significant fibrosis (0.61 vs 0.70, p<0.001) and cirrhosis
(0.64 vs 0.78, p<0.001). The FIB-4 AUROC in patients aged<30 years was lower than
that in patients aged>=30 years for significant fibrosis (0.57 vs 0.65, p<0.001)
and cirrhosis (0.63 vs 0.72, p<0.001). Using specificity>=90%, the APRI cut-off
in patients aged<30 years was lower than patients aged>=30 years for significant
fibrosis (1.0 vs 1.2) and cirrhosis (1.2 vs 1.5). Using sensitivity>=90%, the
APRI cut-off in patients aged<30 years was also lower than patients aged>=30
years for significant fibrosis (0.2 vs 0.4) and cirrhosis (0.3 vs 0.5). Using
specificity>=90%, the FIB-4 cut-off in patients aged<30 years was lower than that
in patients aged>=30 years for significant fibrosis (1.2 vs 2.1) and cirrhosis
(1.4 vs 2.6). Using sensitivity>=90%, the FIB-4 cut-off in patients aged<30 years
was also lower than that in patients aged>=30 years for significant fibrosis (0.5
vs 0.8) and cirrhosis (0.8 vs 1.2). CONCLUSIONS: Evaluation of the diagnostic
performances of APRI and FIB-4 should take age into consideration.
PMID- 28514752
TI - alphaMSH inhibits adipose inflammation via reducing FoxOs transcription and
blocking Akt/JNK pathway in mice.
AB - Alpha melanocyte stimulating hormone (alphaMSH) abates inflammation in multiple
tissues, while Forkhead box proteins O (FoxOs) stimulate inflammatory cascade.
However, the relationship between alphaMSH and FoxOs in adipose inflammation
remains unclear. In this study, we used LPS-induced inflammation model, attempted
to interpret the function of alphaMSH in inflammation and the interactions with
FoxOs. Results indicated that upon inflammatory situation, the secretion of
alphaMSH and the expression of its receptor MC5R were greatly decreased, but
FoxOs expressions were elevated. After the treatment with alphaMSH, LPS-induced
adipose inflammation together with FoxOs expressions was significantly reduced.
Conversely, when Foxo1, Foxo3a or Foxo4 overexpressed in alphaMSH treated
inflammatory mouse model, all the anti-inflammatory impacts of alphaMSH were
found disappeared. We further studied the mechanisms by which alphaMSH exerts its
anti-inflammatory impacts and how FoxOs reverse alphaMSH's function. Foxo4 was
found as a negative regulator for MC5R transcription in alphaMSH inhibited
inflammation. Moreover, a negative role was found of alphaMSH in regulating both
Akt and JNK signal pathways by observing the enhanced the anti-inflammatory
impacts of pathway-specific inhibitors with alphaMSH treatment. Our findings
demonstrate alphaMSH plays a key role in the prevention of adipose inflammation
and inflammatory diseases by down-regulating Akt/JNK signal pathway and
negatively interacting with FoxOs, which brings up alphaMSH as a novel candidate
factor in the adipose anti-inflammation process in obesity.
PMID- 28514754
TI - A hydrophobic residue in the TALE homeodomain of PBX1 promotes epithelial-to
mesenchymal transition of gastric carcinoma.
AB - Pre-B-cell leukemia homeobox 1 (PBX1) was originally identified as a proto
oncogene in human leukemia. Although this protein has been shown to contribute to
cellular development and tumorigenesis, the role of PBX1 in gastric carcinoma
(GC) remains unclear. In this study, we observed increased expression of PBX1 in
GC tissues compared with adjacent normal tissues. This increase in PBX1
expression levels negatively correlated with HOXB9 mRNA expression and was also
associated with malignancy and metastasis. PBX1 promoted proliferation and
metastasis of GC cells both in vitro and in vivo.These phenomena were also
accompanied by epithelial-to-mesenchymal transition (EMT). Additionally, we
observed that PBX1 promotes the expression of tumor growth and angiogenic
factors. A structural model of the PBX1-HOX complex revealed that hydrophobic
binding between PBX1 and the hexapeptide motif might be required for EMT
induction. This analysis also demonstrated that the Phe252 residue in the first
helix of the TALE homeodomain is involved in the latter hydrophobic binding
reaction. In vitro data from PBX1 mutants suggest that PBX1 cannot promote
tumorigenesis of GC cells via EMT induction when Phe252 residues lose
hydrophobicity. It is likely that the presence of this residue is essential in
facilitating hydrophobic binding with the hexapeptide motif. These findings
suggest that PBX1 may be a potential target for GC treatment and this study
provides a platform to elucidate the molecular mechanisms that underpin the role
of PBX1 in GC tumorigenesis.
PMID- 28514755
TI - A novel serum based biomarker panel has complementary ability to preclude
presence of early lung cancer for low dose CT (LDCT).
AB - Low Dosage Computerized Tomography (LDCT) has been shown to improve early
detection of lung cancer and mortality rates in high-risk individuals, which was,
however, limited by specifically coverage for heavy smokers and high rates of
false positivity. Here, we aim to investigate a novel biomarker for early
detection of lung cancer, and further extend to concentrate high-risk subjects
for increasing specificity and coverage of LDCT. We performed retrospective
blinded evaluation of lung cancer and healthy controls in training and validation
cohorts. Macrophage inhibitory cytokine 1 (MIC-1) alone and panel were assessed.
Our data showed the sensitivity of MIC-1 was 72.2% and 67.1% for lung cancer
diagnosis and early diagnosis respectively, at 96.6% specificity, which were
significantly higher than Cyfra21-1, NSE CA125, CEA and SCC. At 90% specificity,
the panel of MIC-1, Cyfra21-1, CA125 and CEA provided 89.5% sensitivity for early
diagnosis of lung cancer, which could be used to concentrate the high-risk
subjects for further LDCT screening. We conclude that MIC-1 have great capacity
in early lung cancer diagnosis. The algorithmic panel of MIC-1, Cyfra21-1, CA125
and CEA could be used to refine the preselection criteria of high-risk subjects,
and thus might facilitate the widespread implementation of LDCT screening.
PMID- 28514756
TI - Elevated CRP levels predict poor outcome and tumor recurrence in patients with
thymic epithelial tumors: A pro- and retrospective analysis.
AB - OBJECTIVE: Scarce information exists on the pathogenesis of thymic epithelial
tumors (TETs), comprising thymomas, thymic carcinomas (TCs) and neuroendocrine
tumors. C-reactive protein (CRP) increases during certain malignancies. We aimed
to investigate the clinical relevance of CRP in patients with TETs. RESULTS:
Pretreatment CRP serum concentrations were significantly elevated in patients
with TETs, particularly TCs and metastatic TETs. After complete tumor resection
CRP serum concentrations were decreased (p = 0.135) but increased significantly
in case of tumor recurrence (p = 0.001). High pretreatment CRP was associated
with significantly worse 5- and 10-year freedom-from recurrence (FFR) (p = 0.010)
and was a negative prognostic factor for FFR (HR 3.30; p = 0.015). IL-6 (not IL
1beta) serum concentrations were significantly elevated in patients with TETs but
we did not detect CRP tissue expression in TETs. MATERIALS AND METHODS:
Pretreatment CRP serum concentrations were retrospectively analyzed from 128
surgical patients (1990-2015). In a subset of 68 patients longitudinal analysis
of CRP was performed. Additionally, immunohistochemical tumor CRP expression and
serum concentrations of interleukin (IL)-6 and IL-1beta were measured.
CONCLUSIONS: Hence, diagnostic measurement of serum CRP might be useful to
indicate highly aggressive TETs and to make doctors consider tumor recurrences
during oncological follow-up.
PMID- 28514757
TI - Adhesion- and stress-related adaptation of glioma radiochemoresistance is
circumvented by beta1 integrin/JNK co-targeting.
AB - Resistance of cancer stem-like and cancer tumor bulk cells to radiochemotherapy
and destructive infiltration of the brain fundamentally influence the treatment
efficiency to cure of patients suffering from Glioblastoma (GBM). The interplay
of adhesion and stress-related signaling and activation of bypass cascades that
counteract therapeutic approaches remain to be identified in GBM cells. We here
show that combined inhibition of the adhesion receptor beta1 integrin and the
stress-mediator c-Jun N-terminal kinase (JNK) induces radiosensitization and
blocks invasion in stem-like and patient-derived GBM cultures as well as in GBM
cell lines. In vivo, this treatment approach not only significantly delays tumor
growth but also increases median survival of orthotopic, radiochemotherapy
treated GBM mice. Both, in vitro and in vivo, effects seen with beta1
integrin/JNK co-inhibition are superior to the monotherapy. Mechanistically, the
in vitro radiosensitization provoked by beta1 integrin/JNK targeting is caused by
defective DNA repair associated with chromatin changes, enhanced ATM
phosphorylation and prolonged G2/M cell cycle arrest. Our findings identify a
beta1 integrin/JNK co-dependent bypass signaling for GBM therapy resistance,
which might be therapeutically exploitable.
PMID- 28514758
TI - BCL2L10 positive cells in bone marrow are an independent prognostic factor of
azacitidine outcome in myelodysplastic syndrome and acute myeloid leukemia.
AB - Azacitidine (AZA), the reference treatment for most higher-risk myelodysplastic
(MDS) patients can also improve overall survival (OS) in elderly acute myeloid
leukemia (AML) patients ineligible for intensive chemotherapy, but reliable
biological markers predicting response and OS in patients treated with AZA are
lacking. In a preliminary study, we found that an increase of the percentage of
BCL2L10, an anti-apoptotic member of the bcl-2 family, was correlated with AZA
resistance. In this study, we assessed prospectively by flow cytometry the
prognostic value of BCL2L10 positive bone marrow mononuclear cells in 70 patients
(42 MDS and 28 AML), prior to AZA treatment.In patients with baseline marrow
blasts below 30%, the baseline percentage of bone marrow BCL2L10 positive cells
inversely correlated with response to AZA and OS independently of the
International Prognostic Scoring System (IPSS) and IPSS-revised (IPSS-R).
Specifically, OS was significantly lower in patients with more than 10% BCL2L10
positive cells (median 8.3 vs 22.9 months in patients with less than 10%
positivity, p = 0,001). In summary, marrow BCL2L10 positive cells may be a
biomarker for azacitidine response and OS, with a potential impact in clinical
practice.
PMID- 28514761
TI - Zbtb38 is a novel target for spinal cord injury.
AB - Spinal cord injury (SCI) is currently incurable since treatments applied to
clinic are limited to minimizing secondary complications and the mechanisms of
injury-induced spinal cord damage are poorly understood. Zbtb38, also called
CIBZ, is highly expressed in spinal cord and it functions as a negative regulator
in SCI-induced apoptosis. We show here that Zbtb38 is downregulated under
endoplasmic reticulum (ER) stress, which promotes ER stress-associated apoptosis
in human bone marrow neuroblastoma cells. In the traumatic SCI mice, ER stress
presented in injured spinal cord induced repression of Zbtb38 expression and
triggered Zbtb38-mediated apoptosis. ChIP-QPCR analysis revealed that ATF4, an ER
stress inducible transcription factor, directly activated Zbtb38 transcription by
binding to the Zbtb38 promoter. However, this binding was significantly reduced
following SCI, leading to a sharp decrease in Zbtb38 expression. Restoring Zbtb38
function in injured spinal cord by injection of lentivirus containing Zbtb38 into
SCI mice, significantly alleviated secondary damage of spinal cord with decreased
ER stress-associated apoptosis and partially recovered spinal cord functions.
These findings demonstrate that restoration of Zbtb38 expression can reduce
secondary tissue damage after SCI, and suggest that a therapeutic strategy for
targeting Zbtb38 may promote functional recovery of spinal cord for patients with
SCI.
PMID- 28514759
TI - Charge reversible calcium phosphate lipid hybrid nanoparticle for siRNA delivery.
AB - Bcl-2 gene is an important target to treat lung cancer. The small interference
RNA (siRNA) of Bcl-2 gene (siBcl-2) can specifically silence Bcl-2 gene. However,
naked siBcl-2 is difficult to accumulate in the tumor tissue to exert its
activity. In this paper, a calcium phosphate lipid hybrid nanoparticle that
possessed charge reversible property was prepared to enhance the activity of
siBcl-2 in vivo. The average diameter and zeta potential of siBcl-2 loaded
calcium phosphate lipid hybrid nanoparticles (LNPS@siBcl-2) were 80 nm and -13 mV
at pH7.4 whereas the diameter and zeta potential changed to 1506 nm and +9 mV at
pH5.0. LNPS@siBcl-2 could efficiently deliver siBcl-2 to the cytoplasm and
significantly decreased the expression of Bcl-2 in A549 cells. Moreover, the in
vivo experimental results showed that most of the Cy5-siBcl-2 accumulated in
tumor tissue after LNPS@Cy5-siBcl-2 was administered to tumor-bearing mice by
tail vein injection. Meanwhile, the expression of Bcl-2 was decreased but the
expression of the BAX and Caspase-3 was increased in tumor tissue. LNPS@siBcl-2
significantly inhibited the growth of tumor in tumor-bearing mice without any
obvious systemic toxicity. Thus, the charge reversible calcium phosphate lipid
hybrid nanoparticle was an excellent siBcl-2 delivery carrier to improve the
activity of siBcl-2 in vivo. LNPS@siBcl-2 has potential in the treatment of lung
cancer.
PMID- 28514762
TI - Novel circular RNA expression profiles reflect progression of patients with
hypopharyngeal squamous cell carcinoma.
AB - Circular RNAs (circRNAs), a novel class of endogenous noncoding RNAs, have been
shown to have important roles in a number of diseases, including several types of
cancers. We hypothesized that circRNAs are involved in the pathogenesis of
hypopharyngeal squamous cell carcinoma (HSCC). To test our hypothesis, we
initially compared the expression profiles of circRNAs in 4 paired HSCC and
adjacent normal tissue samples by using a circRNA microarray. The microarray data
showed that 2392 circRNAs, including 1304 upregulated and 1088 downregulated
circRNA transcripts, were significantly dysregulated in the HSCC tissues. The 10
most dysregulated circRNAs from the microarray analysis were further validated in
another 32 pairs of specimens using quantitative real-time polymerase chain
reaction assays. These circRNAs might sponge microRNAs (miRNAs) in predicted
circRNA-miRNA-mRNA networks. Bioinformatics analysis was also performed to
predict possible pathways in which these networks might be involved. Finally, we
analyzed the interaction between validated circRNAs and their potential cancer
related miRNA targets. We are the first to comprehensively delineate the
expression profiles of circRNAs in HSCC and to provide potential candidates for
future mechanism studies. Our study is potentially of critical significance in
uncovering the roles of circRNAs in HSCC.
PMID- 28514764
TI - TRIM32 affects the recovery of motor function following spinal cord injury
through regulating proliferation of glia.
AB - Both the extrinsic environmental factors and intrinsic neuronal mechanisms limit
the axonal regeneration after spinal cord injury (SCI). However, the underlying
molecular mechanisms remain unclear. In the present study, we identify tripartite
motif protein 32 (TRIM32), an E3 ubiquitin ligase, which is barely detected in
glial cells in the normal uninjured spinal cord, exhibits strong expression in
both astrocytes and microglia following SCI. We further observe that deficiency
of TRIM32 results in increased numbers of astrocytes and microglia, which is
accompanied by enhanced proliferation of both cells and increased secretion of
interleukin (IL)-1 and IL-10. The axonal regeneration is impaired in the spinal
cord of TRIM32-/- mice following SCI, which is indicated by increased distances
of the corticospinal tracts (CST) fiber to the lesion site and less axonal
sprouting. We further show that deficiency of TRIM32 results in delay motor
recovery following SCI. Therefore, TRIM32 is a novel essential positive factor
modulating axonal regeneration and the recovery of motor function following SCI,
possibly through suppressing proliferation of glial cells.
PMID- 28514765
TI - BMX/Etk promotes cell proliferation and tumorigenicity of cervical cancer cells
through PI3K/AKT/mTOR and STAT3 pathways.
AB - Bone marrow X-linked kinase (BMX, also known as Etk) has been reported to be
involved in cell proliferation, differentiation, apoptosis, migration and
invasion in several types of tumors, but its role in cervical carcinoma remains
poorly understood. In this study, we showed that BMX expression exhibits a
gradually increasing trend from normal cervical tissue to cervical cancer in situ
and then to invasive cervical cancer tissue. Through BMX-IN-1, a potent and
irreversible BMX kinase inhibitor, inhibited the expression of BMX, the cell
proliferation was significantly decreased. Knockdown of BMX in HeLa and SiHa
cervical cancer cell lines using two different silencing technologies, TALEN and
shRNA, inhibited cell growth in vitro and suppressed xenograft tumor formation in
vivo, whereas overexpression of BMX in the cell line C-33A significantly
increased cell proliferation. Furthermore, a mechanism study showed that
silencing BMX blocked cell cycle transit from G0/G1 to S or G2/M phase, and
knockdown of BMX inhibited the expression of p-AKT and p-STAT3. These results
suggested that BMX can promote cell proliferation through PI3K/AKT/mTOR and STAT3
signaling pathways in cervical cancer cells.
PMID- 28514772
TI - Risk of Onset of Hematological Malignancies in Patients Infected with the
Hepatitis B Virus: Results from a Large-Scale Retrospective Cohort Study in
China.
AB - The hepatitis B virus (HBV) is a major global issue, because an increased risk of
hepatocellular carcinoma among patients infected with HBV is well established.
Recently, it has been suggested that HBV is associated with other human cancers.
However, the association between HBV and the risk of onset of hematological
malignancies remains controversial. The aim of this large-scale retrospective
cohort study was to evaluate the association between HBV infection and
hematological malignancies. A retrospective analysis of 86,115 newly admitted
patients at Shanghai Ruijin Hospital was performed. A cohort of patients
previously exposed to HBV (n = 1,874) and a cohort of individuals without a
positive test for anti-hepatitis B core antigen (anti-HBc; n = 45,118) were
compared to assess the risk of hematological malignancies. Anti-HBc was positive
in 61.2% cases and 54.3% controls (p = 0.0001). The risk of B cell non-Hodgkin's
lymphoma, acute lymphoblastic leukemia, and multiple myeloma was higher in the
HBV-infected cohort than in the non-HBV-infected cohort. In conclusion, patients
infected with HBV have a substantially increased risk of hematological
malignancies.
PMID- 28514771
TI - Istaroxime, a potential anticancer drug in prostate cancer, exerts beneficial
functional effects in healthy and diseased human myocardium.
AB - : The current gold standard for prostate cancer treatment is androgen deprivation
therapy and antiandrogenic agents. However, adverse cardiovascular events
including heart failure can limit therapeutic use. Istaroxime, which combines Na+
K+-ATPase (NKA) inhibition with sarco/endoplasmic reticulum Ca2+-ATPase 2a
(SERCA2a) stimulation, has recently shown promising anti-neoplastic effects in
prostate cancer (PC) models and may also improve cardiac function. Considering
the promising anticancer effects of istaroxime, we aimed to assess its functional
effects on human myocardium. RESULTS: Istaroxime and strophanthidin elicited dose
dependent positive inotropic effects with a decline in developed force at
supraphysiological concentrations in human atrial, nonfailing, and failing
ventricular (ToF) myocardium. Diastolic force and RT50% did not change after
exposure to both drugs. The maximal developed force in our in-vitro model of
heart failure (ToF) was significantly higher after istaroxime administration.
Such a difference did not occur in atrial or nonfailing ventricular trabeculae
and was not applicable to the diastolic force. MATERIALS AND METHODS: Human
atrial and ventricular trabeculae were isolated from nonfailing hearts and hearts
of infants with tetralogy of Fallot (ToF), which were used as an in-vitro model
of heart failure. The samples were electrically stimulated and treated with
increasing concentrations of istaroxime and strophanthidin (10 nM-1 MUM).
Systolic and diastolic force development and relaxation parameters (RT50%) were
analyzed. CONCLUSIONS: Combined NKA inhibition/SERCA2a stimulation increases
contractility in atrial, nonfailing, and failing myocardium. Considering that
heart failure is a potential side effect of current PC treatments, especially in
elderly patients, istaroxime might combine beneficial cardiac and anti-cancer
properties.
PMID- 28514773
TI - A Feasibility Study of the Full Outpatient Conduction of Hematopoietic
Transplants in Persons with Multiple Sclerosis Employing Autologous Non
Cryopreserved Peripheral Blood Stem Cells.
AB - BACKGROUND: With the goal of achieving immune system reset, autologous
hematopoietic stem cell transplantations have been performed in patients with
multiple sclerosis (MS). MATERIAL AND METHODS: Two hundred and eighty-six
consecutive patients with MS were autografted in a single center using non-frozen
peripheral blood stem cells (PBSCs), on an outpatient basis and conditioning with
cyclophosphamide and rituximab. The protocol was registered in ClinicalTrials.gov
identifier NCT02674217. RESULTS: One hundred and ninety-four females and 92 males
were included; the median age was 47. All procedures were started on an
outpatient basis and only 8 persons needed to be admitted to the hospital during
the procedure. In order to obtain at least 1 * 106/kg viable CD34 cells, 1-4
aphereses were performed (median 1). The total number of viable CD34+ cells
infused ranged between 1 and 19.2 * 106/kg (median 4.6). Patients recovered above
0.5 * 109/L absolute granulocytes on median day 8 (range 0-12). Two individuals
needed red blood cells but none needed platelet transfusions. There were no
transplant-related deaths and the 128-month overall survival of the patients is
100%. In 82 persons followed up for 3 or more months, the Expanded Disability
Status Scale diminished from a mean of 5.2-4.9, the best results being obtained
in relapsing-remitting and primary progressive MS. CONCLUSIONS: It is possible to
conduct autotransplants for patients with MS employing non-frozen PBSCs and
outpatient conduction. Additional information is needed to assess the efficacy of
these procedures in the treatment of patients with MS.
PMID- 28514774
TI - Demonstration of 5-Methylcytosine-Rich DNA Sequences in Chiroptera.
AB - 5-Methylcytosine-rich heterochromatic regions were demonstrated in metaphase
chromosomes of 5 species of Chiroptera by indirect immunofluorescence using a
monoclonal anti-5-methylcytosine antibody. These species belong to 4 genera and 2
families and are characterized by divergent karyotypes. One species
(Glauconycteris beatrix) has an extremely low diploid chromosome number of 2n =
22 with only meta- to submetacentric elements and remarkably large amounts of
constitutive heterochromatin located in the centromeric and pericentromeric
regions of all chromosome pairs. Two species (G. beatrix and Neoromicia cf.
guineensis) possess X-autosome translocations. In all species, the
hypermethylated chromosome segments correspond to constitutive heterochromatin,
and the numbers and positions of hypermethylated chromosome segments in the
karyotypes are constant and species-specific. In some species (Pipistrellus
hesperidus, Neoromicia cf. somalicus), there are several smaller chromosome pairs
in which the bright anti-5-methylcytosine antibody labeling is not restricted to
constitutively heterochromatic regions but is observed along the whole lengths of
these chromosomes. The nature of these additional hypermethylated regions is
discussed. The analysis of 5-methylcytosine-rich chromosome regions elucidates
valuable data for chiropteran cytogenetics and reflects the high pace of
evolution of the repetitive DNA fraction in their genomes.
PMID- 28514775
TI - Metallic and Polymeric Scaffold: Too Soon to Pension the Drug-Eluting Stent.
PMID- 28514776
TI - Predictive Factors for Developing Venous Thrombosis during Cisplatin-Based
Chemotherapy in Testicular Cancer.
AB - BACKGROUND: Malignancies and cisplatin-based chemotherapy are both known to
correlate with a high risk of venous thrombotic events (VTT). In testicular
cancer, the information regarding the incidence and reason of VTT in patients
undergoing cisplatin-based chemotherapy is still discussed controversially.
Moreover, no risk factors for developing a VTT during cisplatin-based
chemotherapy have been elucidated so far. PATIENTS AND METHODS: We
retrospectively analyzed 153 patients with testicular cancer undergoing cisplatin
based chemotherapy at our institution for the development of a VTT during or
after chemotherapy. Clinical and pathological parameters for identifying possible
risk factors for VTT were analyzed. The Khorana risk score was used to calculate
the risk of VTT. Student t test was applied for calculating the statistical
significance of differences between the treatment groups. RESULTS: Twenty-six out
of 153 patients (17%) developed a VTT during chemotherapy. When we analyzed the
risk factors for developing a VTT, we found that Lugano stage >=IIc was
significantly (p = 0.0006) correlated with the risk of developing a VTT during
chemotherapy. On calculating the VTT risk using the Khorana risk score model, we
found that only 2 out of 26 patients (7.7%) were in the high-risk Khorana group
(>=3). CONCLUSION: Patients with testicular cancer with a high tumor volume have
a significant risk of developing a VTT with cisplatin-based chemotherapy. The
Khorana risk score is not an accurate tool for predicting VTT in testicular
cancer.
PMID- 28514777
TI - Direct Measurement of Tissue Oxygenation in Neonates via Resonance Raman
Spectroscopy: A Pilot Study.
AB - BACKGROUND: The ability to monitor tissue oxygenation in neonates remains a
challenge due to limited blood supply and the reliance on invasive procedures.
Resonance Raman spectroscopy noninvasively measures tissue oxygenation (RRS
StO2). Peripheral tissue oxygenation using this novel technology has not been
described in neonates. OBJECTIVES: To examine the relationship between short-term
RRS-StO2 measurements and central venous saturation (ScvO2) and pulse oximetry
(SpO2) in preterm and term neonates. METHODS: Ninety-seven term neonates had
buccal and plantar RRS-StO2 measurements performed. In 15 preterm neonates,
similar measurements were obtained in conjunction with ScvO2 in the first week of
life. Simultaneous SpO2 and heart rate were also recorded. RESULTS: In healthy
neonates, buccal RRS-StO2 values negatively correlated with the day of life. No
correlation existed between buccal and plantar RRS-StO2 values and ScvO2 or SpO2.
Greater intra-patient plantar RRS-StO2 variability was seen in preterm neonates
with increasing respiratory support. CONCLUSIONS: Neonatal RRS-StO2 measurements
are feasible short term but do not correlate with ScvO2 and SpO2. Healthy
neonates had greater differences and variability in RRS-StO2 values, illustrating
an evolving microcirculation not detected with pulse oximetry. Greater RRS-StO2
variability in sick neonates requiring respiratory support may indicate
microcirculatory instability despite being within target SpO2 ranges. Further
study is needed to establish if RRS-StO2 monitoring is an accurate representation
of tissue oxygenation.
PMID- 28514778
TI - Validation of the Five-Factor Model of the Arabic Version of the Positive and
Negative Syndrome Scale in Schizophrenia.
AB - BACKGROUND: The Positive and Negative Syndrome Scale (PANSS) is a widely used
assessment for patients with schizophrenia across clinical and research settings.
This scale allows the classification of the psychotic symptoms to better
understand the psychopathology in patients with schizophrenia. There are no
available data on the different components of psychopathology in Arab patients
with schizophrenia. OBJECTIVES: This study examined the factor structure of the
validated Arabic version of the PANSS in a sample of Arab patients with
schizophrenia. METHODS: The Arabic version of the PANSS was administered to 101
patients with schizophrenia, and principal component analysis (PCA) was carried
out after the cross-cultural adaptation and validation of this version. RESULTS:
This sample had more males (66.3%) than females (33.7%) with a mean age of 35.03
years (SD = 9.99). PCA showed that 28 items loaded on 5 components: cognitive,
negative, excited, depressed and positive. These factors explained 63.19% of
variance. The 2 remaining items, grandiosity and somatic concerns, did not load
well on any of these components. CONCLUSION: Our results support the common 5
dimension PANSS model shown in other cultures with different languages.
Nevertheless, there were minor differences, which could reflect cultural or
semantic differences.
PMID- 28514779
TI - Low Back Pain in Pregnancy: Investigations, Management, and Role of Neuraxial
Analgesia and Anaesthesia: A Systematic Review.
AB - BACKGROUND: Low back pain (LBP) is commonly experienced during pregnancy and is
often poorly managed. There is much ambiguity in diagnostic work-up, appropriate
management and decision-making regarding the use of neuraxial analgesia and
anaesthesia during labour and delivery in these patients. This systematic review
summarises the evidence regarding investigations, management strategies and
considerations around performing neuraxial blocks for pregnant women with LBP.
METHODS: We searched 3 databases and reviewed literature concerning LBP in
pregnancy with regards to diagnostic modalities, management strategies and use of
neuraxial techniques for facilitating labour and delivery. RESULTS: In all, we
included 78 studies in this review, with 32 studies concerning diagnostic
investigations, 56 studies involving management strategies, and 4 studies
regarding the use of neuraxial techniques for labour and delivery. SUMMARY: MRI
is the safest investigative modality for LBP in pregnancy. Antenatal educational
programmes, exercise and steroid injections into the epidural space or sacroiliac
joints may help with pain management. Worsening neurological deficits, vertebral
fractures and tumours may need surgical management. There is limited evidence on
challenges of performing neuraxial blocks in the peripartum period for analgesia
and anaesthesia, but there is a potential for increased risk of neurological
complications in parturients with pre-existing neurological deficits.
PMID- 28514780
TI - Two Distinct BCL2 Rearrangements, Each Observed in 2 Independent Subclones,
Evolving from a Founder Clone with Trisomy 12 in a Unique Case of Chronic
Lymphocytic Leukemia/Small Lymphocytic Lymphoma.
PMID- 28514781
TI - Hepcidin: Homeostasis and Diseases Related to Iron Metabolism.
AB - Iron is an essential metal for cell survival that is regulated by the peptide
hormone hepcidin. However, its influence on certain diseases is directly related
to iron metabolism or secondary to underlying diseases. Genetic alterations
influence the serum hepcidin concentration, which can lead to an iron overload in
tissues, as observed in haemochromatosis, in which serum hepcidin or defective
hepcidin synthesis is observed. Another genetic imbalance of iron is iron
refractory anaemia, in which serum concentrations of hepcidin are increased,
precluding the flow and efflux of extra- and intracellular iron. During the
pathogenesis of certain diseases, the resulting oxidative stress, as well as the
increase in inflammatory cytokines, influences the transcription of the HAMP gene
to generate a secondary anaemia due to the increase in the serum concentration of
hepcidin. To date, there is no available drug to inhibit or enhance hepcidin
transcription, mostly due to the cytotoxicity described in the in vitro models.
The proposed therapeutic targets are still in the early stages of clinical
trials. Some candidates are promising, such as heparin derivatives and
minihepcidins. This review describes the main pathways of systemic and genetic
regulation of hepcidin, as well as its influence on the disorders related to iron
metabolism.
PMID- 28514782
TI - A Systematic Review and Meta-Analysis of Influenza A Virus Infection During
Pregnancy Associated with an Increased Risk for Stillbirth and Low Birth Weight.
AB - BACKGROUND/AIMS: Impaired pregnancy outcomes, such as low birth weight are
associated with increased disease risk in later life, however little is known
about the impact of common infectious diseases during pregnancy on birth weight.
The study had two aims: a) to investigate risk factors of influenza virus
infection during pregnancy, and b) to analyze the impact of influenza virus
infection on pregnancy outcome, especially birth weight. METHODS: Prospective and
retrospective observational studies found in PubMed, MEDLINE, Embase, Google
Scholar, and WangFang database were included in this meta analysis. Data of
included studies was extracted and analyzed by the RevMan software. RESULTS:
Pregnant women with anemia (P=0.004, RR=1.46, 95% CI: 1.13-1.88), obesity
(P<0.00001, RR=1.35, 95% CI: 1.25-1.46) and asthma (P<0.00001, RR=1.99, 95% CI:
1.67-2.37) had higher rates of influenza virus infection. Regarding birth
outcomes, influenza A virus infection did not affect the likelihood for cesarean
section. Mothers with influenza had a higher rate of stillbirth (P=0.04, RR=2.36,
95% CI: 1.05-5.31), and their offspring had low 5-minute APGR Scores (P=0.009,
RR=1.39, 95% CI: 1.08-1.79). Furthermore, the rate for birth weight < 2500g
(P=0.04, RR=1.71, 95% CI: 1.03-2.84) was increased. CONCLUSION: Results of this
study showed that anemia, asthma and obesity during pregnancy are risk factors
influenza A virus infection during pregnancy. Moreover, gestational influenza A
infection impairs pregnancy outcomes and increases the risk for low birth weight,
a known risk factor for later life disease susceptibility.
PMID- 28514783
TI - Dialysis Access as an Area of Improvement in Elderly Incident Hemodialysis
Patients: Results from a Cohort Study from the International Monitoring Dialysis
Outcomes Initiative.
AB - BACKGROUND: Commencing hemodialysis (HD) using a catheter is associated with a
higher risk of adverse outcomes, and early conversion from central-venous
catheter (CVC) to arteriovenous fistula/graft (non-CVC) improves outcomes. We
investigated CVC prevalence and conversion, and their effects on outcomes during
the first year of HD in a multinational cohort of elderly patients. METHODS:
Patients >=70 years from the MONDO Initiative who commenced HD between 2000 and
2010 in Asia-Pacific, Europe, North-, and South-America and survived at least 6
months were included in this investigation. We stratified by age (70-79 years
[younger] vs. >=80 years [older]) and compared access types (at first and last
available date) and their changes. We studied the association between access at
initiation and conversion, respectively, and all-cause mortality using Kaplan
Meier curve and Cox regression, and predicted the absence of conversion from
catheter to non-CVC using adjusted logistic regression. RESULTS: In 14,966
elderly, incident HD patients, survival was significantly worse when using a CVC
at all times. In Europe, the conversion frequency from CVC to non-CVC was higher
in the younger fraction. Conversion from non-CVC to CVC was associated with
worsened outcomes only in the older fraction. CONCLUSION: These results
corroborate the need for early HD preparation in the elderly HD population.
Treatment of elderly patients who commence HD with a CVC should be planned
considering aspects of individual clinical risk assessment. Differences in
treatment practices in predialysis care specific to the elderly as a population
may influence access care and conversion rate.
PMID- 28514784
TI - Effects of Intensive Statin Therapy on Left Ventricular Function in Patients with
Myocardial Infarction and Abnormal Glucose Tolerance.
AB - OBJECTIVES: Abnormal glucose tolerance in patients with acute myocardial
infarction (AMI) is associated with greater mortality and adverse cardiovascular
effects. As statins possess a range of beneficial pleiotropic effects on the
cardiovascular system, we sought to assess the cardioprotective effects of
statins on left ventricular function in patients with AMI in relation to
glycometabolic state. METHODS: In a prospective, randomized trial, 140 patients
with AMI were randomized to intensive statin therapy receiving statin loading
with 80 mg of rosuvastatin followed by 40 mg daily or standard statin therapy.
Patients were assessed with an oral glucose tolerance test and their left
ventricular (LV) function was assessed with speckle-tracking echocardiography
measuring regional longitudinal systolic strain (RLSS) in the infarct area.
RESULTS: Overall RLSS in the infarct area improved by a mean (+/-SD) of -4.22%
(+/-5.19) in the intensive-care group and -2.48% (+/-4.01) in the usual-care
group after 1 month (p = 0.047). In patients with abnormal glucose tolerance,
RLSS improved by -5.01% (+/-5.28) in the intensive-care group and -2.15% (+/
4.22) in the usual-care group (p = 0.01). CONCLUSIONS: Early high-dose statin
treatment improved RLSS in the infarct area in patients with AMI, and a trend of
greater improvement was seen in patients with abnormal glucose tolerance.
PMID- 28514785
TI - Effect of Age on the Association of Vascular Access Type with Mortality in a
Cohort of Incident End-Stage Renal Disease Patients.
AB - BACKGROUND/AIMS: All hemodialysis (HD) patients are generally recommended to
create a fistula first; but to create a mature arteriovenous fistula (AVF) can be
challenging in elderly individuals. It is unclear if elderly incident HD patients
derive a survival benefit from an AVF over an arteriovenous graft (AVG) or a
tunneled central venous catheter (TDC). METHODS: We examined the association of
vascular access type (AVF, AVG, and TDC with and without a maturing AVF/AVG at
dialysis transition) at HD initiation with all-cause, cardiovascular (CV), and
infection-related mortality in 46,786 US veterans using Cox models with
adjustment for confounders. Effect modification by age was examined by examining
associations in pre-specified age subgroups (<60, 60-<70, 70-<80, and >=80 years
old), and by including interaction terms. RESULTS: Patients numbering 8,940 (19%)
started HD with an AVF, 1,090 (3%) with an AVG, 8,262 (18%) with a TDC and a
maturing AVF/AVG and 28,494 (61%) with a TDC without a maturing AVF/AVG. A total
of 13,303 all-cause, 4,392 CV, and 1,058 infection-related deaths were observed
in the first year after HD transition. Compared to patients with AVF, those with
AVG and TDC with and without maturing AVF/AVG had incrementally higher overall
risk of all-cause mortality and CV mortality. Only TDC use was associated with
higher infection-associated mortality. These associations were not modified by
age. CONCLUSION: Although most of our patients consisted of male veterans and the
results may not be generalized to the general population, the use of TDCs is
associated with poor outcomes even in the most elderly incident HD patients.
PMID- 28514786
TI - Vascular Proliferation of the Thyroid: Potential Histopathological Pitfalls as a
Consequence of Fine Needle Aspiration.
AB - OBJECTIVE: Fine needle aspiration biopsy (FNAB) can cause reactive
histopathological changes, commonly including haemorrhage and granulation tissue.
The literature describing vascular proliferation after FNAB is sparse. We aimed
to describe neovascularisation in thyroid gland specimens as a consequence of
FNAB. STUDY DESIGN: We analysed all thyroid histopathological specimens from the
Fimlab Laboratories collected between 2010 and 2013 for neovascularisation and
distortions in the accompanying tissue. We evaluated HE-stained slides and CD31-,
podoplanin-, and Ki-67-immunostained slides. RESULTS: We observed vascular
proliferation in 64 out of 787 specimens (8.1%). In these patients, the mean age
was 62 years, 43 were female and 21 were male. Previous FNAB data were available
in 49 cases (76.6%). In 51 cases (79.7%), the neovascularisation occupied less
than 5% of the thyroid gland area. The vessel dilatation was moderate in 28 cases
(43.8%) and low in 20 cases (31.3%). In tumours, neovessels were detected within
the tumour and in the surrounding tissue. CONCLUSIONS: Post-FNAB tissue samples
include dilated newly formed vessels, which pathologists should differentiate
from rare thyroid vascular tumours. The proposed mechanism is a traumatically
induced haemorrhage followed by haematoma and thrombosis that resolves by
recanalisation. A knowledge of tissue alteration is needed to avoid misdiagnoses.
PMID- 28514787
TI - Delayed Effect of Active Pressure Treatment on Endolymphatic Hydrops.
AB - OBJECTIVE: To identify eventual correlations between the effect of low-pressure
treatment and endolymphatic hydrops in Meniere patients. MATERIAL AND METHODS:
The study group consisted of subjects affected by definite Meniere disease (2015)
and a severe degree of disability, who received a ventilation tube with or
without a low-pressure treatment before undergoing a surgical procedure
(vestibular neurectomy). After the placement of the ventilation tube, the
subjects were either left alone with the tube or received 1 month of self
administered low-pressure therapy with a portable device. In all subjects, an
electrocochleography (ECochG) was performed and specific questionnaires -
Dizziness Handicap Inventory (DHI) and Functional Scale Level (FSL) - were
completed before starting either arm of treatment, at the end of treatment, and
then 3 and 6 months later. RESULTS: All selected subjects presented with an
ECochG pattern that was indicative of endolymphatic hydrops before starting
either treatment. At the end of pressure treatment, 80% showed symptomatic
improvement while maintaining the hydropic ECochG pattern. At the 3-month control
stage, the hydropic pattern resulted normalized (<0.5) in all the improved
subjects. CONCLUSIONS: Although 1 month of low-pressure treatment provided a
positive symptomatological outcome, normalization of the hydropic ECochG
parameters occurred only at a later time. Therefore, it is possible to assume
that endolymphatic hydrops could be concurrent with a non-symptomatic stage of
Meniere disease, and that the anti-hydropic effect of the low-pressure treatment,
if any, would present with a certain delay after its completion.
PMID- 28514788
TI - Embodied pain: grasping a thorny problem?
PMID- 28514789
TI - Growth hormone regulates the sensitization of developing peripheral nociceptors
during cutaneous inflammation: Erratum.
PMID- 28514790
TI - Neuropathic pain phenotyping by international consensus (NeuroPPIC) for genetic
studies: a NeuPSIG systematic review, Delphi survey, and expert panel
recommendations: Erratum.
PMID- 28514791
TI - Impact of targeting adenosine-induced transient venous reconnection in patients
undergoing pulmonary vein isolation for atrial fibrillation: a meta-analysis of
3524 patients.
AB - AIMS: Atrial fibrillation recurrences after pulmonary vein isolation (PVI) are
not uncommon and are frequently related to pulmonary vein reconnection.
Adenosine/ATP can reveal dormant pulmonary vein conduction after PVI. Previous
studies revealed that adenosine-guided Additional ablation could improve
arrhythmia-free survival. We performed a meta-analysis to assess the impact of
additional ablation to eliminate adenosine-induced transient pulmonary vein
reconnection in terms of atrial fibrillation recurrence at follow-up. METHODS:
MEDLINE/PubMed, Cochrane Library and references reporting atrial fibrillation
ablation and adenosine/ATP-following PVI were screened, and studies were included
if they matched inclusion and exclusion criteria. RESULTS: A total of 3524
patients were enrolled with a median follow-up of 13 (6-20) months. Overall, 70%
(60-85) of patients in ATP-guided ablation vs. 63% (48-79) in no ATP-guided
ablation were free of atrial fibrillation at follow-up. Pooled results revealed
that ATP-guided ablation reduced the risk of atrial fibrillation recurrence of
42% [odds ratio (OR) 0.58, 0.41-0.81], but this result was primary because of the
contribution of retrospective over-randomized studies [OR 0.48 (0.35-0.65) vs.
0.76 (0.42-1.40), respectively]. 3.2% of patients experienced an adverse event.
ATP-guided ablation is related to a nonsignificant increase in fluoroscopy time
(OR 1.71, 0.98-2.96) and to a significant increase in procedure time (OR 2.84,
1.32-6.09). CONCLUSION: Additional ablation aiming to eliminate adenosine-induced
transient pulmonary vein reconnection failed to reduce the risk of atrial
fibrillation recurrence at follow-up. Moreover, although adenosine-guided PVI is
not affected by an augmented risk of adverse events, it is associated with a NS
increased fluoroscopy exposure and significantly longer procedure duration.
Further studies are required to identify the actual role of adenosine in PVI.
PMID- 28514793
TI - Acute Treatment Patterns for Lower Extremity Trauma in the United States: Flaps
versus Amputation.
PMID- 28514794
TI - [Editor's Comment].
PMID- 28514792
TI - Autonomic dysregulation in burnout and depression: evidence for the central role
of exhaustion.
AB - Objectives Given the important role of the autonomic nervous system (ANS) in
stress regulation, astonishingly little is known about ANS functioning in
burnout, a condition arising after prolonged exposure to work-related stress. The
current study sought to investigate ANS modulation, as indexed by vagally
mediated heart rate variability (HRV), in relation to burnout symptomatology to
(i) distinguish associations between the three dimensions of burnout [emotional
exhaustion (EE), cynicism, reduced personal accomplishment] and (ii) investigate
overlap in associations with depressive symptomatology. Methods Assessments of
vagally-mediated HRV (ie, root mean square of successive differences, RMSSD) were
conducted in a large population-based sample from the Dresden Burnout Study
[N=410, mean age 42.2, standard deviation (SD) 11.2 years; 33.4% male]. Vagally
mediated HRV was assessed for 90 seconds during an emotionally-arousing situation
(venipuncture, recumbent), a 335-second recumbent recovery period, and a 335
second seated resting condition. Results Results from multiple linear regression
analyses revealed that EE was negatively related to RMSSD during venipuncture
(=beta -0.11, P=0.03) and the seated rest (beta= -0.09, P=0.04) even after
accounting for established ANS modulators (eg, age, body mass index). This
pattern was not observed for the other dimensions of burnout. Exploratory
analyses of depressive symptomatology further revealed that RMSSD was
significantly and inversely associated with burnout-related symptoms but not with
the core criteria of depression (eg, depressed mood). Conclusions This study
presents evidence for a link between exhaustion and reduced vagal function, both
in burnout and depression, suggesting that ANS modulations may not be disorder
specific but rather a psychophysiological correlate of an underlying feature
shared by both conditions.
PMID- 28514796
TI - ?
PMID- 28514795
TI - ?
PMID- 28514797
TI - ?
PMID- 28514798
TI - [Swallowing Disorders in Tracheo(s)tomized Patients].
AB - Objective Since many years it has been conjectured that tracheotomy/tracheostomy
interferes with swallowing and leads to a higher risk of aspiration. The aim of
this review was to contribute to the discussion whether there is a causal
relationship between tracheotomy/tracheostomy and dysphagia or only a
chronological concomitance. Material and Methods Citations for this review rest
upon a research in PubMed data base of the National Center for Biotechnology
Information (NCBI). Results Effects of tracheostomy/tracheotomy as well as
effects of different cannulas on motoric and sensory aspects of deglutition have
been reviewed. Most papers focused on aspiration. Reported data were extremely
heterogeneous. Finally no causal relationship between tracheotomy and dysphagia
could be demonstrated. Conclusions Tracheo(s)tomized patients require a special
awareness in respect to concomitant dysphagia. However, swallowing problems are
considered to be primarily caused rather by underlying diseases than by the
existence of the tracheostomy itself.
PMID- 28514799
TI - [Rare Differential Diagnosis of Tinnitus and Hearing Impairment].
PMID- 28514800
TI - [From the Experts Office: Hearing Impairment due Vibration, Infrasound,
Ultrasound and/or Bodysound?]
PMID- 28514802
TI - ?
PMID- 28514801
TI - [Psychooncological Treatment of Patients with Head and Neck Cancer].
AB - The aim of psychooncological interventions are to facilitate coping with the
disease, to improve the psychological well-being and quality of life of the
cancer patients as well as the strengthening of personal and social
resources.Apart from general strain going along with oncological diseases and its
treatment, patients with head and neck cancer often also suffer from impairment
of the most basic human functions (speech, swallowing, food intake).Patients with
head and neck cancer are one of the most distressed and burdened groups of cancer
patients.Psychooncological interventions apply proven psychological and
psychotherapeutic methods and techniques.Psychooncological treatment is based on
the close interdisciplinary cooperation of different professional groups.
PMID- 28514803
TI - ?
PMID- 28514804
TI - [Changes in the Use of Health Insurance Services before and after a Father-Child
Measure].
AB - Introduction Since 2002 inpatient preventive and rehabilitative measures for
fathers and their children (F-C-M) are available in the German health system (SS
24 and 41 SGB V). So far there is no data on health disorders of the fathers in F
C-M. The aim of this study is to examine whether participants of F-C-M are more
prone to health problems than fathers who are not participating in F-C-M and
whether participation in F-C-M contributes to improved health. To do so, the
change in the use of outpatient care services is examined and compared to the use
of mentioned services by fathers who are not participating in an F-C-M. The
research project is based on the routine data of AOK-Niedersachsen (AOKN).
Methods Outpatient diagnoses and medications that were billed one year before and
one year after the measure are used as outcome variables for outpatient use. The
test sample (N=179) includes all fathers who participated in a F-C-M in 2005-2009
and were insured throughout. For these fathers, a comparative group of fathers
who had not participated in a F-C-M (N=717) was formed in parallel. Results The
investigation has shown that the participants of the F-C-M received more
diagnoses and medications before and after the measure than fathers without F-C
M. Fathers under 40 years mostly got fewer diagnoses and medications after the
measure than before the measure, whereas older people showed a higher claim after
the measure. The participants of the F-C-M mainly have more F-diagnoses than
fathers without F-C-M. In addition to that the increase in I-diagnoses and the
increase in cardiovascular drugs are striking compared to the previous year.
Conclusion The increased use of the statutory health insurance benefits of
participants of the F-C-M compared to non-participants indicates that the F-C-M
is a health-impaired group of insured people. The high number of F-diagnoses
further illustrates that the participants are particularly affected in this
indication area. A positive effect of the measure is shown by the fact that
younger fathers made reduced use of health insurance benefits, while in the case
of older participants a treatment requirement was still predominant or was
revealed in the context of the measure.
PMID- 28514805
TI - Expression and Histopathological Significance of Disabled-2 in Aldosterone
Producing Adenoma.
AB - The current pathological diagnosis of aldosterone-producing adenoma (APA) is
challenging because no histological markers of aldosterone production are
available in routine practice. A previous study demonstrated that Disabled-2
(DAB2) is a specific marker of the zona glomerulosa (ZG) in rodents. The aim of
the present study was to investigate the significance of immunohistochemical
staining to detect DAB2 in the adrenal tissue of patients with APA. We
investigated the expression of DAB2 in 36 adrenal glands with APA, 23 adrenal
glands with cortisol-producing adenoma (CPA), and 33 adrenal glands with non
functioning adenoma (NFA). Immunohistochemical staining was performed using anti
DAB2 antibodies on paraffin-embedded sections. We analysed the expression of DAB2
semi-quantitatively by scoring staining intensity, and assessed the correlation
of this information with the clinical findings. DAB2 mRNA expression in adenoma
tissues was evaluated by RT-PCR. DAB2 was highly expressed in the ZG in normal
human adrenal glands. DAB2 expression was heterogeneous in APA, with spotted,
strong staining noted in most samples (25 of 36 APA). CPA and NFA also exhibited
extensive low or moderate DAB2 expression. DAB2 mRNA was significantly increased
and positively correlated with CYP11B2 in APA (p<0.05). In APA, the DAB2 score
adjusted for tumour volume was positively correlated with plasma aldosterone
(p<0.05). Patients with low or moderate DAB2 staining more frequently exhibited
high blood pressure and were diagnosed at a younger age compared with patients
with high DAB2 staining. The present study clearly demonstrates that DAB2 is a
specific marker of the ZG in normal human adrenal glands but that DAB2
immunostaining is not sufficiently powerful for histopathological diagnosis of
APA. DAB2 might be involved in excessive aldosterone biosynthesis and correlate
with specific clinical characteristics of APA patients.
PMID- 28514806
TI - Human Epicardial Fat Expresses Glucagon-Like Peptide 1 and 2 Receptors Genes.
AB - Epicardial adipose tissue (EAT) is an easily measurable visceral fat of the heart
with unique anatomy, functionality, and transcriptome. EAT can serve as a
therapeutic target for pharmaceutical agents targeting the fat. Glucagon-like
peptide-1 (GLP-1) and GLP-2 analogues are newer drugs showing beneficial
cardiovascular and metabolic effects. Whether EAT expresses GLP- 1 and 2
receptors (GLP-1R and GLP-2R) is unknown. RNA-seq analysis and quantitative real
time polymerase chain reaction (qRT-PCR) were performed to evaluate the presence
of GLP-1R and GLP-2R in EAT and subcutaneous fat (SAT) obtained from 8 subjects
with coronary artery disease and type 2 diabetes mellitus undergoing elective
cardiac surgery. Immunofluorescence was also performed on EAT and SAT samples
using Mab3f52 against GLP-1R. Our RNA-sequencing (RNA-seq) analysis showed that
EAT expresses both GLP-1R and GLP-2R genes. qRT-PCR analysis confirmed that GLP
1R expression was low but detected by 2 different sets of intron-spanning
primers. GLP-2R expression was detected in all patients and was found to be 5
fold higher than GLP-1R. The combination of accurately spliced reads from RNA-seq
and successful amplification using intron-spanning primers indicates that both
GLP-1R and GLP-2R are expressed in EAT. Immunofluorescence clearly showed that
GLP-1R is present and more abundant in EAT than SAT. This is the first time that
human EAT is found to express both GLP-1R and GLP-2R genes. Pharmacologically
targeting EAT may induce beneficial cardiovascular and metabolic effects.
PMID- 28514807
TI - Can Transcranial Direct Current Stimulation Modulate Psychophysiological Response
in Sedentary Men during Vigorous Aerobic Exercise?
AB - This study evaluated whether transcranial direct current stimulation (tDCS) could
change physiological and psychological responses during vigorous exercise with a
constant load. 13 sedentary males (23.0+/-4.2 years; 25.6+/-4.2 kg/m2) took part
in this randomized, crossed-over, sham-controlled, and double-blinded study.
Participants underwent 2 sessions with anodal or sham tDCS (2 mA, 20 min) applied
before exercise over the left temporal cortex targeting the left insular cortex.
The exercise was performed at vigorous intensity (%HRmax 81.68+/-6.37) for 30
min. Heart rate (HR), rating of perceived exertion (RPE) and affective responses
(pleasure/displeasure) were recorded at every 5 min. Additionally, heart rate
variability (HRV) was measured before, immediately after and 60 min after the end
of exercise. A 2-way repeated measure ANOVA showed that tDCS improved HRV neither
at rest nor after exercise (p>0.15). Similarly, HR, RPE, and affective responses
were not enhanced by tDCS during vigorous exercise (p>0.23). The findings of this
study suggest that tCDS does not modulate either HRV at rest nor HR, RPE and
affective responses during exercise. Transcranial direct current stimulation's
efficiency might depend on the participants' levels of physical fitness and
parameters of stimulation (e. g., duration, intensity, and arrangement of
electrodes).
PMID- 28514808
TI - Physiological Dynamic Apnea Responses in Relation to Apnea Capacity in
Triathletes.
AB - The aim was to assess the cardiac, arterial oxygen saturation, lactate, hormonal
and Borg rating of perceived exertion (RPE) responses to acute apnea in relation
to apnea capacity in 18 middle-aged triathletes. Subjects were monitored while
swimming two 50-m freestyle exercise trials with fins at maximal speed: with
normal frequency breathing (NB) and with complete apnea (Ap); the latter was used
to assess apnea capacity. The subjects with significant alteration in swimming
performance inducing a time increase greater than 2.5% during Ap vs. NB were put
in the group: bad apnea capacity (Bad Ap); the others, who showed no significant
alteration in performance, were put in the group: Good Ap. Under apnea, both
groups showed a decrease in arterial oxygen saturation (p<0.05). In Ap
conditions, only Bad Ap had a significant lower maximal heart rate vs. NB
(p<0.05), with lower blood lactate (p<0.05) and arm stroke frequency (p<0.01). No
change in saliva hormonal concentrations was found during the experiment for both
groups, whereas RPE responses were increased in the Good Ap group under Ap vs. NB
conditions. In conclusion, a good apnea capacity seems to be associated with
lower cardiovascular and metabolic apnea alterations in middle-aged
recreationally-trained triathletes.
PMID- 28514809
TI - ?
AB - Whilst Critical Speed (CS) has been successfully translated from the laboratory
into the field, this translation is still outstanding for the related maximum
running distance (D'). Using iso-duration exhaustive laboratory and field runs,
this study investigated the potential interchangeable use of both parameters, D'
and CS. After an incremental exercise test, 10 male participants (age: 24.9+/-2.1
yrs; height: 180.8+/-5.8 cm; body mass: 75.3+/-8.6 kg; V VO2peak 52.9+/-3.1
mL?min-1?kg-1) performed 3 time-to-exhaustion runs on a treadmill followed by 3
exhaustive time-trial runs on a-400 m athletics outdoor track. Field time-trial
durations were matched to their respective laboratory time-to-exhaustion runs. D'
and CS were calculated using the inverse-time model (speed=D'/t+CS). Laboratory
and field values of D' and CS were not significantly different (221+/-7 m vs.
225+/-72 m; P=0.73 and 3.75+/-0.36 m?s-1 vs. 3.77+/-0.35 m?s-1, P=0.68), and they
were significantly correlated (r=0.86 and 0.94). The 95% LoA were +/-75.5 m and
+/-0.24 m?s-1 for D' and CS, respectively. Applying iso-durations provides non
significant differences for D' and CS and a significant correlation between
conditions. This novel translation method can consequently be recommended to
coaches and practitioners, however a questionable level of agreement indicates to
use D' with caution.
PMID- 28514810
TI - Totally Minimally Invasive Esophagectomy and Gastric Pull-Up Reconstruction with
an Intrathoracic Circular Stapled Anastomosis with a Team of Two (Surgeon and
Assistant Only).
AB - Totally minimally invasive esophagectomy (MIE) is nowadays en vogue.1 2 3 4 5
There are several reports showing that already partial minimally invasive
esophagectomies (hybrid esophagectomies) with a laparoscopic approach and open
transthoracic resection are beneficial for patients due to the reduced operative
trauma. Also for total MIE several groups have reported benefits for patients in
terms of morbidity and quality of life.1 5 However, different approaches and
experiences of different esophageal surgery groups are hardly comparable and thus
do not allow a simple answer in favor of a specific total MIE technique. To
enlighten the field of total MIE, we present the technique as we perform this
procedure nearly weekly in our department. The described MIE technique is safe
and feasible. Changing to this demonstrating technique, we did not have any
mortality so far, even in the first 30 cases. Especially for surgeons who plan to
switch from the open surgical technique toward hybrid, MIE or robotic-assisted
MIE.
PMID- 28514812
TI - Prevention of Seroconversion after HIV-Infected Needle Stick.
PMID- 28514811
TI - Reply by the Authors of the Original Article.
PMID- 28514813
TI - ?
PMID- 28514814
TI - [Possibilities and Limitations of OCT-Angiography in Patients with Central Serous
Chorioretinopathy].
AB - Purpose Central serous chorioretinopathy (CSC) is a commonly acquired maculopathy
characterized by the accumulation of subretinal fluid at the posterior pole. This
study aims to analyze optical coherence tomography angiography (OCTA) findings in
patients with acute and chronic CSC and to compare them to conventional imaging
methods. Methods A series of 43 consecutive eyes of 29 patients diagnosed with
CSC and 18 eyes of 9 healthy control subjects were included in this retrospective
study. The OCTA images were assessed and compared to conventional fluorescence
(FAG) and indocyanine green angiography (ICG). Results All CSC patients
demonstrated abnormal areas of focal hypo- and hyperperfusion in the
choriocapillaris. These were particularly evident in patients with chronic
atrophic CSC. FAG and ICG imaging revealed leakage points in 10 of 43 eyes and
choroidal neovascularization (CNV) in 3 of 43 eyes. OCTA imaging confirmed
leakage points in 4 out of 10 cases and choroidal neovascularization in 2 out of
3 cases. In one case, OCTA demonstrated a CNV which was not detectable by
FAG/ICG. Conclusion OCTA reveals areas of focal hypo- and hyperperfusion in the
choriocapillaris in patients with CSC. Due to the inability to detect plasma
flow, OCTA is not suitable to detect leakage points in CSC with confidence.
However, OCTA reliably detects CNV in CSC even in the absence of exudative
activity and may, therefore, represent an important supplement in the diagnosis
of CSC.
PMID- 28514815
TI - [Otto Wichterle and Soft Contact Lenses].
PMID- 28514816
TI - [Novel Thixotropic Silicone Oils - The Ketchup Bottle Approach for Silicone Oil
Endotamponades].
AB - Silicone oil endotamponades need to be injected and removed in a reasonable time
and under moderate pressure conditions. However, due to ever-decreasing sizes of
incisions and trocars, injection and removal of highly viscous silicone oils is
very time-consuming. To address resulting problems like longer treatment times or
hypotony, thixotropic silicone oils were developed. These oils are characterized
by a diminished viscosity under constant mechanical stress; whilst there is
pressure or vacuum acting on it, the oils will become more fluid and, therefore,
much easier to be applied. Once the force is being removed from the oil, it will
automatically return to its initial viscosity after a short time.
PMID- 28514817
TI - [The Role of Intraocular Pressure Fluctuation in the Development and Progression
of Glaucoma].
AB - Intraocular pressure fluctuation has been discussed as a risk factor for glaucoma
development and glaucoma progression. Two clinical trials (Sweden and USA) have
evaluated the relationship between IOP and glaucoma progression. Both studies
will be discussed in this review. Additionally, some smaller studies exist that
are mentioned and discussed as well. This review summarizes the most important
studies.
PMID- 28514818
TI - [Diabetes - a Continually Increasing Challenge].
PMID- 28514819
TI - [39-year-old Woman with Eruptive Skin Lesions on the Face].
PMID- 28514821
TI - [The Way to Closed Loop - Dream and Reality].
AB - An old dream of patients with type 1 diabetes and medical teams alike is a fully
automated insulin therapy. Available sensor-augmented insulin-pumps are able to
intervene in insulin therapy by reducing the dose. Aim of several studies is to
add an algorithm to the interaction of pump and sensor, so that insulin doses can
be regulated fully automatically. Totally closed loop systems are currently not
yet available for outpatient use. Hybrid closed loop systems have been approved
in the US. They can improve the metabolic status of patients with type 1
diabetes. Risks are similar to sensor-augmented insulin-pump therapy. Patients'
detailed education will continue to be essential for success.
PMID- 28514820
TI - [Diagnostic Approach to Manifestation of Type 1 Diabetes mellitus].
AB - The incidence of type 1 and type 2 diabetes mellitus has been increasing
simultaneously. Formerly, these two patients' populations could be differentiated
easily, but now, due to the overlapping of both groups, specified diagnostics are
necessary. In order to substantiate a suspicion on diabetes, quantifying venous
plasma glucose is the gold standard in diagnostics. As a precaution,
determination of the HbA1c and OGTT is recommended. It is not necessary to
determinate antibodies in every new case of diabetes. In patients with a vague
constellation of clinical picture diagnosis can be ensured by findings of uric
ketones, BGA, IA-2- and GAD-antibodies and optionally C-peptide. Often T1DM is
associated with PGAS. Therefore, once manifestation of diabetes is detected,
screening autoimmune disorders is recommended directly and regularly every two
years.
PMID- 28514822
TI - [Cardiovascular Effects of Antidiabetic Therapies].
AB - Type 2- diabetes mellitus (T2DM) represents a major risk factor for
cardiovascular complications and mortality. Strict glucose control in the early
course of the disease prevents cardiovascular complications only in the long run.
Non-medical therapies (diet, exercise, body weight reduction) bear little
evidence for positive cardiovascular effects.Bariatric surgery is not number one
choice in therapy of T2DM. Metformin seems to provide positive cardiovascular
effects. Insulin seems to be cardiovascular neutral, as well as the DPP4
inhibitors Saxagliptin, Sitagliptin and Alogliptin. Concerning GLP-1-RAs,
Lixisenatide has a neutral cardiovascular effect, whereas Liraglutide and
Semaglutide reduce cardiovascular outcomes. The SGLT2-inhibitor Empagliflozin
reduces cardiovascular mortality, total mortality and hospitalization by heart
failure.
PMID- 28514823
TI - [Fulminant Course of a Clostridium Perfringens Infection with Pathognomonic CT
finding].
AB - History and clinical findings A 74-year old woman was accepted by the emergency
room with severe chest and abdominal pain. She complained about regurgitation
after ingestion of food followed by sharp pain in her breast. Investigations A
first examination of the patient showed a tachypnoea und tachycardia up to 122
beats per minute, the body temperature measured on admission was 38.7 degrees C.
Due to hemolysis only a few of the requested parameters could be evaluated. CRP
was increased with 8.32 mg/dl. The hemoglobin dropped from 12.0 g/dl to 10.3 g/dl
during 4 hours. A computed tomography scan was done because of severe worsening
of the patient's condition. The CT scan showed two cavities in the right lobe of
the liver filled with gas. Treatment and course Initial antibiotic therapy with
Ceftriaxon was immediately started. During her stay in the emergency room the
patient showed a severe worsening of her condition. Therefore a CT scan was
initiated after the abdominal ultrasound revealed nothing specific. During the CT
examination the patient stopped breathing sufficiently, followed by hematuria and
vomiting a large amount of blood. The patient died 8.5 hours of an irreversible
cardiovascular failure after admission to the hospital. Conclusion A rapid
decline of the patient's condition in addition to hemolysis and a gas-filled
liver necrosis are pathognomonic signs for an infection with clostridium
perfringens which requires immediate treatment. Only an immediate surgical
intervention in combination with an adapted antibiotic increases chances of
survival in patients with clostridia.
PMID- 28514825
TI - [The Pulmonary Vein Isolation is the Primary Therapy for Paroxysmal Atrial
Fibrillation].
PMID- 28514824
TI - [Attaching an Insulin Pump].
PMID- 28514826
TI - [Pulmonary Vein Isolation in Paroxysmal Atrial Fibrillation is - Still - not a
Primary Therapy of Paroxysmal Atrial Fibrillation].
PMID- 28514827
TI - ?
PMID- 28514828
TI - ?
PMID- 28514829
TI - Does Hofstetter's equation predict the real amplitude of accommodation in
children?
AB - PURPOSE: The aim was to determine the distribution and associated factors of
accommodative amplitude (AA) in six- to 12-year-old children and compare the
results with those calculated using Hofstetter's formula. METHODS: In a cross
sectional study in 2015, random sampling was done from urban and rural
populations of Shahroud, northern Iran. Participating schoolchildren were
examined for manifest, cycloplegic and subjective refraction, as well as
uncorrected vision and visual acuity. The AA was measured with Donders' push-up
method using a ruler. The near point of convergence (NPC) was also measured.
RESULTS: Of the 6,624 selected children, 5,620 participated in the study and
after applying the exclusion criteria, the final analyses were done on data from
5,444 schoolchildren. The mean age of the final sample was 9.24 +/- 1.71 years
(from six to 12 years) and 53.6 per cent (n = 2,919) were boys. Mean measured AA
was 14.44 D (95 per cent confidence interval [CI]: 14.33-14.55). In all age
groups, the mean measured AA was less than the predicted mean value calculated
with the Hofstetter's equation. Mean measured AA was 14.44 D (95 per cent CI:
14.28-14.59) and 14.45 D (95 per cent CI: 14.29-14.6) in boys and girls,
respectively (p = 0.926). AA significantly declined with age (coefficient: -0.18,
95 per cent CI: -0.23 to -0.12, p < 0.001). Mean AA in emmetropic, myopic and
hyperopic children was 14.31 D, 17.30 D and 14.87 D, respectively. Older age
(coefficient = -0.18), living in rural areas (coefficient = -0.48) and NPC
(coefficient = 0.47) inversely related with AA and higher AA was associated with
a shift of the spherical equivalent refraction toward myopia (coefficient =
0.41). CONCLUSION: The differences among groups with different types of
refractive error and high AA in children with myopia are important findings of
this study. The results of the present study suggest that Hofstetter's formula
provides inaccurate AA estimates in children and thus, the interpretation of this
index requires further population-based studies in different racial and ethnic
groups.
PMID- 28514830
TI - Association of maternal serum PAPP-A levels, nuchal translucency and crown-rump
length in first trimester with adverse pregnancy outcomes: retrospective cohort
study.
AB - OBJECTIVE: Are first trimester serum pregnancy-associated plasma protein-A (PAPP
A), nuchal translucency (NT) and crown-rump length (CRL) prognostic factors for
adverse pregnancy outcomes? METHOD: Retrospective cohort, women, singleton
pregnancies (UK 2011-2015). Unadjusted and multivariable logistic regression.
OUTCOMES: small for gestational age (SGA), pre-eclampsia (PE), preterm birth
(PTB), miscarriage, stillbirth, perinatal mortality and neonatal death (NND).
RESULTS: A total of 12 592 pregnancies: 852 (6.8%) PTB, 352 (2.8%) PE, 1824
(14.5%) SGA, 73 (0.6%) miscarriages, 37(0.3%) stillbirths, 73 perinatal deaths
(0.6%) and 38 (0.30%) NND. Multivariable analysis: lower odds of SGA [adjusted
odds ratio (aOR) 0.88 (95% CI 0.85,0.91)], PTB [0.92 (95%CI 0.88,0.97)], PE [0.91
(95% CI 0.85,0.97)] and stillbirth [0.71 (95% CI 0.52,0.98)] as PAPP-A increases.
Lower odds of SGA [aOR 0.79 (95% CI 0.70,0.89)] but higher odds of miscarriage
[aOR 1.75 95% CI (1.12,2.72)] as NT increases, and lower odds of stillbirth as
CRL increases [aOR 0.94 95% CI (0.89,0.99)]. Multivariable analysis of three
factors together demonstrated strong associations: a) PAPP-A, NT, CRL and SGA, b)
PAPP-A and PTB, c) PAPP-A, CRL and PE, d) NT and miscarriage. CONCLUSIONS:
Pregnancy-associated plasma protein-A, NT and CRL are independent prognostic
factors for adverse pregnancy outcomes, particularly PAPP-A and SGA with lower
PAPP-A associated with increased risk. (c) 2017 John Wiley & Sons, Ltd.
PMID- 28514833
TI - Antinociceptive effect of (-)-alpha-bisabolol in nanocapsules.
AB - This study aimed to develop and to evaluate the antinociceptive effect of a drug
delivery system containing (-)-alpha-bisabolol (BISA). Nanocapsules containing
BISA (BISA-NC) were prepared using acetylated galatomannan. Particle size
distribution was determined by atomic force microscopy, zeta potential
measurement and photon correlation spectroscopy. Corneal nociception was induced
by topical application of 5M NaCl and the nociceptive behavior was characterized
by eye wiping in mice. Molecular docking was conducted on the TRPV1 channel.
Nanocapsules showed mean particle sizes between 94.44 and 105.44nm and the zeta
potential of was -1.34mV. Animals pretreated with BISA-NC (200mg/mL) had a
significant reduction (**p<0.01) in the number of nociceptive behaviors. Docking
study indicated an interaction between BISA and TRPV1. This study indicates that
BISA-NC may be useful for producing eye drops for the treatment of ocular pain.
PMID- 28514831
TI - Hypericum perforatum extract attenuates behavioral, biochemical, and
neurochemical abnormalities in Aluminum chloride-induced Alzheimer's disease
rats.
AB - Alzheimer's disease (AD) is a progressive and ultimately fatal neurodegenerative
diseases. Aluminum, a neurotoxic metal, is considered as the pathological
hallmark and contributing factor of AD. Hypericum perforatum extract (HPE) is a
neuroprotective agent that can prevent neurodegenerative pathologies through
antioxidants, anti-inflammatory and regulating neurotransmitter release in animal
model of neuropathy. The present study aimed to identify the potential
neuroprotective of HPE on AlCl3-induced AD rats. Rats were treated with AlCl3 for
90days to induce behavioral, biochemical, and neurochemical similar to AD. From
31thday, the rats were treated with HPE for 60days. Our results showed HPE
improved cognitive function in AlCl3-induced AD rats, and attenuated AlCl3
induced increase in acetylcholinesterase activity and glutamic acid level as well
as decreased in noradrenaline and dopamine level. In addition, HPE reversed AlCl3
induced hippocampal pathology including amyloid-beta (Abeta) accumulation
(elevated Abeta42 level and amyloid plaques), oxidative stress (increased
reactive oxygen species level and thiobarbituric acid reactive substances level,
decreased glutathione level and superoxide dismutase activity) and
neuroinflammatory (increased mRNA expressions of Interleukin-1beta, Interleukin
6, Tumor necrosis factor-alpha and major histocompatibility complex class II) in
hippocampus of rats. Thus, HPE is conferred neuroprotection against AlCl3-induced
AD like pathology.
PMID- 28514832
TI - Anti-obesity effects of tea from Mangifera indica L. leaves of the Uba variety in
high-fat diet-induced obese rats.
AB - Due to the high content of bioactive compounds, herbal teas are being
investigated as adjuvant in chronic disease management. Studies have shown that
mango leaf tea contain mangiferin, total phenolics and antioxidants, compounds
with many functional properties. Therefore, this study aims to evaluate the anti
obesity effects of tea from Mangifera indica L. leaves, Uba variety (TML), in
obese rats fed a high-fat diet (HFD). For this, adult male Wistar rats were
divided into three groups (n=8): the control group (fed AIN-93 diet), obese group
(fed a HFD) and treated group (fed a HFD and supplemented with TML for 8 weeks).
We analysed biometric measures and serum biochemical parameters of metabolic
control, inflammation and oxidative stress biomarkers, histomorphometry of
visceral adipose tissue and mRNA expression of peroxisome proliferator-activated
receptor gamma co-activator 1 alpha (PPAR-gamma), lipoprotein lipase (LPL) and
fatty acid synthase (FAS). The consumption of TML (24.7+/-2.1mL/day) exerted
antioxidant and anti-inflammatory effects, increasing total antioxidant capacity
and interleukin-10 serum concentrations, reduced abdominal fat accumulation,
upregulated PPAR-gamma and LPL and downregulated FAS expression. Our data suggest
that TML has therapeutic potential in treating obesity and related diseases
through regulating the expression of transcriptional factors and enzymes
associated with adipogenesis.
PMID- 28514834
TI - Antitumor activity of Brazilian red propolis fractions against Hep-2 cancer cell
line.
AB - Continuous increases in the rates of tumor diseases have highlighted the need for
identification of novel and inexpensive antitumor agents from natural sources. In
this study, we investigated the effects of enriched fraction from hydroalcoholic
Brazilian red propolis extract against Hep-2 cancer cell line. Initially 201
fractions were arranged in 12 groups according to their chromatographic
characteristics (A-L). After an in vitro cell viability screening, J and L were
further selected as promising enriched fractions for this study. The chemical
characterization was performed and Biochanin A, Formononetin, and Liquiritigenin
compounds were quantified. Through MTT viability assay and morphological changes
observed by Giemsa and DAPI staining, the results showed that red propolis
inhibited cancer cells growth. Flow cytometry results indicated effects that were
partly mediated through programmed cell death as confirmed by externalization of
phosphatidylserine, DNA cleaved assay, increase at SUB G1-G0 phase in cell cycle
analysis and loss of mitochondrial membrane potential. In conclusion, our results
demonstrated that red propolis enriched fractions promoted apoptotic effects in
human cancer cells through the mechanisms involving mitochondrial perturbation.
Therefore, red propolis fractions contain candidate agents for adjuvant cancer
treatment, which further studies should elucidate the comprehensive mechanistic
pathways.
PMID- 28514835
TI - Genistein has beneficial effects on hepatic steatosis in high fat-high sucrose
diet-treated rats.
AB - Genistein, a kind of phytoestrogen abundant in soybeans, is beneficial for
alleviating non-alcoholic fatty liver disease (NAFLD), but the specific mechanism
was not clearly understood. This study was designed to determine the effect of
genistein on NAFLD and explore the possible mechanism. 36 male Sprague-Dawley
rats were divided into 4 groups: the control group, high fat-high sucrose diet
(HFS) group, HFS with 4mg/kg body weight genistein, and HFS with 8mg/kg body
weight genistein. 12 weeks later, serum and hepatic lipid profiles, liver
histopathological examination were characterized. The protein levels of liver AMP
activated protein kinase (AMPK), phosphorylation of AMPK (p-AMPK), acetyl-CoA
carboxylase (ACC), phosphorylation of ACC (p-ACC) and sterol regulatory element
binding protein 1 (SREBP-1) were determined by western blot. mRNA expressions of
fatty acid synthase gene (FAS) and glycerol-3-phosphate acyltransferase (GPAT),
peroxisome proliferator-activated receptor alpha (PPARalpha), carnitine palmitoyl
transfer enzyme-1 (CPT-1) and acyl-CoA oxidase (ACO) were measured by reverse
transcription polymerase chain reaction (RT-PCR). Results showed that genistein
effectively improved serum and hepatic lipid metabolism and diminished fat
accumulation in liver. And the protein level of hepatic p-AMPK and p-ACC were
increased, but SREBP-1 was decreased by genistein. Meanwhile, the mRNA levels of
FAS and GPAT were lower, but PPARalpha, CPT-1, ACO were higher in rats treated
with genistein compared with HFS group. Collectively, genistein can improve
hepatic steatosis via activating AMPK, thus promoting fatty acid oxidation and
inhibiting lipid synthesis in liver.
PMID- 28514836
TI - Oxidation of organic contaminant in a self-driven electro/natural
maghemite/peroxydisulfate system: Efficiency and mechanism.
AB - Electro-assisted iron-mediated persulfate (PS) activation process has been
successfully employed to oxidize organic contaminant. However, a majority of iron
based catalysts used for PS activation was synthesized through complicated or
demanding procedures and may have potential risks on environment during the
preparation process. Herein, natural maghemite (NM) which is abundant on the
earth was employed to activate peroxydisulfate (PDS) in an electrolytic cell. The
voltage was provided by microbial fuel cell (MFC) instead of external power as
reported in the previous studies, so as to establish a self-driven
electro/natural maghemite/PDS system (MFC/NM/PDS) for the oxidation of acid
orange 7 (AO7). The results showed that above 90% removal efficiency of AO7 was
achieved in a wide range of pH (3.0-9.0) after 100min reaction. Singlet oxygen
was identified for the first time during PDS activation and surface bound sulfate
radicals served as the dominant active species responsible for AO7 oxidation. The
underlying mechanism of AO7 elimination in the MFC/NM/PDS system was elucidated
through quenching tests, electron paramagnetic resonance (EPR) and X-ray
photoelectron spectroscopy (XPS) techniques. The variation of TOC and
cytotoxicity to Escherichia coli was explored. The intermediate products formed
were identified using LC-TOF-MS technique and a possible pathway of AO7
degradation was proposed.
PMID- 28514837
TI - Decomposing an urban soundscape to reveal patterns and drivers of variation in
anthropogenic noise.
AB - Continuous and intermittent noise may have different effects on humans and
wildlife, therefore distinguishing temporal patterns of noise and their drivers
is important for policy regarding both public health and wildlife management. We
visualized patterns and explored land-use drivers of continuous and high
amplitude intermittent sound pressure levels (SPLs) on an urban campus in
Michigan, U.S.A. To visualize patterns of SPLs, we introduce decibel duration
curves (DDCs), which show the cumulative frequency distribution of SPLs and aid
in the interpretation of statistical SPLs (Ln values) that reflect continuous
versus intermittent sounds. DDCs and Ln values reveal that our 24 recording
locations varied in the intensity of both continuous and intermittent noise, with
intermittent high-amplitude sound events in particular contributing to
variability in SPLs over the study site. Time of day influenced both continuous
and intermittent SPLs, as locations relatively close to manmade structures
(buildings, roads and parking lots) experienced higher SPLs as the day
progressed. Continuous SPLs increased with decreasing distance to manmade
structures, whereas intermittent SPLs increased with decreasing distance to roads
and increasing distance to buildings. Thus, different land-use factors influenced
patterns of continuous and intermittent noise, which suggests that different
policy and strategies may be needed to ameliorate their effects on the public and
wildlife.
PMID- 28514838
TI - Macroinvertebrate short-term responses to flow variation and oxygen depletion: A
mesocosm approach.
AB - In Mediterranean rivers, water scarcity is a key stressor with direct and
indirect effects on other stressors, such as water quality decline and inherent
oxygen depletion associated with pollutants inputs. Yet, predicting the responses
of macroinvertebrates to these stressors combination is quite challenging due to
the reduced available information, especially if biotic and abiotic seasonal
variations are taken under consideration. This study focused on the response of
macroinvertebrates by drift to single and combined effects of water scarcity and
dissolved oxygen (DO) depletion over two seasons (winter and spring). A factorial
design of two flow velocity levels - regular and low (vL) - with three levels of
oxygen depletion - normoxia, medium depletion (dM) and higher depletion (dH) -
was carried out in a 5-artificial channels system, in short-term experiments.
Results showed that both stressors individually and together had a significant
effect on macroinvertebrate drift ratio for both seasons. Single stressor effects
showed that macroinvertebrate drift decreased with flow velocity reduction and
increased with DO depletion, in both winter and spring experiments. Despite
single stressors opposing effects in drift ratio, combined stressors interaction
(vL*dM and vL*dH) induced a positive synergistic drift effect for both seasons,
but only in winter the drift ratio was different between the levels of DO
depletion. Stressors interaction in winter seemed to intensify drift response
when reached lower oxygen saturation. Also, drift patterns were different between
seasons for all treatments, which may depend on individual's life stage and
seasonal behaviour. Water scarcity seems to exacerbate the oxygen depletion
conditions resulting into a greater drifting of invertebrates. The potential
effects of oxygen depletion should be evaluated when addressing the impacts of
water scarcity on river ecosystems, since flow reductions will likely contribute
to a higher oxygen deficit, particularly in Mediterranean rivers.
PMID- 28514839
TI - Occurrence of brominated dioxins in a study using various firefighting methods.
AB - The use of different firefighting methods influences how fast a fire is
extinguished and how fast the temperature drops in the area affected by the fire.
These differences may also influence the formation of harmful pollutants during
firefighting of an accidental fire. The aim was to study occurrence of brominated
dibenzo-p-dioxins and furans (PBDD/Fs) in gas and soot during five fire scenarios
resembling a small apartment fire and where different firefighting methods were
used. Samples of gas and soot were taken both during the buildup of the fire and
during the subsequent extinguishing of the fire while using different
firefighting methods (nozzle, compressed air foam system, cutting extinguisher)
and an extinguishing additive. New containers equipped with identical sets of
combustible material were used for the five tests. The use of different
firefighting methods and extinguishing additive induced variations in
concentration and congener profiles of detected PBDD/Fs. The concentration range
of ?PBDD/Fs in gas was 4020-18,700pg/m3, and in soot 76-4092pg/m2. PBDFs were the
predominant congeners and 1,2,3,4,6,7,8-HpBDF was the most abundant congener.
Chlorinated dibenzo-p-dioxins and furans (PCDD/Fs) were also monitored. The
PBDD/Fs contributed with in average 97% to the total (PCDD/Fs plus PBDD/Fs) toxic
equivalents, in soot and gas. During extinguishing, the shorter time the
temperature was around 300 degrees C, the lower occurrence of PBDD/Fs. In the
study the firefighting methods showed a difference in how effectively they
induced a temperature decrease below 300 degrees C in the fire zone during
quenching, where cutting extinguishing using additive and the compressed air foam
system showed the fastest drop in temperature.
PMID- 28514840
TI - Plastics in the North Atlantic garbage patch: A boat-microbe for hitchhikers and
plastic degraders.
AB - Plastic is a broad name given to different polymers with high molecular weight
that impact wildlife. Their fragmentation leads to a continuum of debris sizes
(meso to microplastics) entrapped in gyres and colonized by microorganisms. In
the present work, the structure of eukaryotes, bacteria and Archaea was studied
by a metabarcoding approach, and statistical analysis associated with network
building was used to define a core microbiome at the plastic surface. Most of the
bacteria significantly associated with the plastic waste originated from non
marine ecosystems, and numerous species can be considered as hitchhikers, whereas
others act as keystone species (e.g., Rhodobacterales, Rhizobiales,
Streptomycetales and Cyanobacteria) in the biofilm. The chemical analysis
provides evidence for a specific colonization of the polymers.
Alphaproteobacteria and Gammaproteobacteria significantly dominated mesoplastics
consisting of poly(ethylene terephthalate) and polystyrene. Polyethylene was also
dominated by these bacterial classes and Actinobacteria. Microplastics were made
of polyethylene but differed in their crystallinity, and the majorities were
colonized by Betaproteobacteria. Our study indicated that the bacteria inhabiting
plastics harboured distinct metabolisms from those present in the surrounding
water. For instance, the metabolic pathway involved in xenobiotic degradation was
overrepresented on the plastic surface.
PMID- 28514841
TI - Endoscopic Management of Pancreatic Fluid Collections in Children.
AB - The incidence of acute pancreatitis in children has increased over the last few
decades. The development of pancreatic fluid collection is not uncommon after
severe acute pancreatitis, although its natural course in children and
adolescents is poorly understood. Asymptomatic fluid collections can be safely
observed without any intervention. However, the presence of clinically
significant symptoms warrants the drainage of these fluid collections. Endoscopic
management of pancreatic fluid collection is safe and effective in adults. The
use of endoscopic ultrasound (EUS)-guided procedure has improved the efficacy and
safety of drainage of pancreatic fluid collections, which have not been well
studied in pediatric populations, barring a scant volume of small case series.
Excellent results of EUS-guided drainage in adult patients also need to be
verified in children and adolescents. Endoprostheses used to drain pancreatic
fluid collections include plastic and metal stents. Metal stents have wider
lumens and become clogged less often than plastic stents. Fully covered metal
stents specifically designed for pancreatic fluid collection are available, and
initial studies have shown encouraging results in adult patients. The future of
endoscopic management of pancreatic fluid collection in children appears
promising. Prospective studies with larger sample sizes are required to establish
their definitive role in the pediatric age group.
PMID- 28514842
TI - Gender difference in radiotherapy-induced carotid stenosis.
AB - Radiotherapy (RT) is often the first choice of treatment for cancer of the
larynx. Studies have shown that the incidence of carotid stenosis (CS) after
radiotherapy of laryngeal cancer is increasing, and that gender difference in
radiotherapy-induced side effects exist. Thus, we examined the gender difference
in the incidence of CS and the impact of microinflammatory factors after
radiotherapy. We reported this study on patients who received radiotherapy as
part of the treatment for laryngeal cancer in the Jilin Province in China. One
hundred sixty-four males and 152 females were treated with radiotherapy between
2006 and 2016. The carotid diameter was determined by measuring carotid intima
media thickness in the common, external and internal carotid artery.
Microinflammatory conditions were assessed by measuring the level of high
sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis
factor-alpha (TNF-alpha). Other studied risk factors included age, treatment
modalities, radiation dose and energy, the height of the radiation field, and the
follow-up time. CS was detected in 161 (50.9%) of the 316 patients. Carotid
stenosis was mainly clinically unsuspected, two patients had anamnesis of
unconsciousness. Importantly, fewer women (36.1%) had CS than men (64.6%)
(p=0.004). Furthermore, male patients showed higher serum levels of hs-CRP, IL-6,
and TNF-alpha. Taken together, our study suggested that women underoing
radiotherapy of laryngeal cancer are less likely to have CS than men. Therefore,
routine assessment after irradiation of laryngeal cancer seems necessary for
clinical detection of asymptomatic CS, particularly in male patients.
PMID- 28514843
TI - Single-Cell Real-Time Visualization and Quantification of Perylene
Bioaccumulation in Microorganisms.
AB - Bioaccumulation of perylene in Escherichia coli and Staphylococcus aureus was
visualized and quantified in real time with high sensitivity at high temporal
resolution. For the first time, single-molecule fluorescence microscopy (SMFM)
with a microfluidic flow chamber and temperature control has enabled us to record
the dynamic process of perylene bioaccumulation in single bacterial cells and
examine the cell-to-cell heterogeneity. Although with identical genomes,
individual E. coli cells exhibited a high degree of heterogeneity in perylene
accumulation dynamics, as shown by the high coefficient of variation (C.V =
1.40). This remarkable heterogeneity was exhibited only in live E. coli cells.
However, the bioaccumulation of perylene in live and dead S. aureus cells showed
similar patterns with a low degree of heterogeneity (C.V = 0.36). We found that
the efflux systems associated with Tol C played an essential role in perylene
bioaccumulation in E. coli, which caused a significantly lower accumulation and a
high cell-to-cell heterogeneity. In comparison with E. coli, the Gram-positive
bacteria S. aureus lacked an efficient efflux system against perylene. Therefore,
perylene bioaccumulation in S. aureus was simply a passive diffusion process
across the cell membrane.
PMID- 28514844
TI - Measurement of the 30Si Mole Fraction in the New Avogadro Silicon Material by
Neutron Activation and High-Resolution gamma-Spectrometry.
AB - The use of new silicon single crystals highly enriched in 28Si recently produced
for the upcoming redetermination of the Avogadro constant requires knowledge of
their molar masses. The isotopic composition data are collected independently in
different laboratories but all using the virtual element technique with
multicollector inductively coupled plasma mass spectrometers. In this framework,
the comparison of the results with an independent measurement of the amount of at
least one of the depleted isotopes is useful to limit hidden systematic errors.
To this aim, the 30Si mole fraction of a sample of the new material was measured
using a relative measurement protocol based on instrumental neutron activation
analysis. The protocol is similar to that previously applied with the AVO28
silicon material used for the last determination of the Avogadro constant value
with the exception that unknown and standard samples are not coirradiated. The
x(30Si) = 5.701 * 10-7 mol mol-1 estimate is close to the expected one and is
given with a standard uncertainty of 8.8 * 10-9 mol mol-1. This value, if
adopted, gives a contribution to the relative standard uncertainty of the
Avogadro constant of 6.3 * 10-10.
PMID- 28514845
TI - In Vivo Mercury Demethylation in a Marine Fish (Acanthopagrus schlegeli).
AB - Mercury (Hg) in fish has attracted public attention for decades, and
methylmercury (MeHg) is the predominant form in fish. However, the in vivo MeHg
demethylation and its influence on Hg level in fish have not been well-addressed.
The present study investigated the in vivo demethylation process in a marine fish
(black seabream, Acanthopagrus schlegeli) under dietary MeHg exposure and
depuration and quantified the biotransformation and interorgan transportation of
MeHg by developing a physiologically based pharmacokinetic (PBPK) model. After
exposure, we observed a 2-fold increase of the whole-body inorganic Hg (IHg),
indicating the existence of an in vivo demethylation process. The results
strongly suggested that the intestine played a predominant role in MeHg
demethylation with a significant rate (6.6 +/- 1.7 day-1) during exposure,
whereas the hepatic demethylation appeared to be an extremely slow (0.011 +/-
0.001 day-1) process and could hardly affect the whole-fish Hg level. Moreover,
demethylation in the intestine served as an important pathway for MeHg
detoxification. Our study also pointed out that in vivo MeHg demethylation could
influence Hg level and speciation in fish although food is the major pathway for
Hg accumulation. Enhancing in vivo MeHg biotransformation (especially in the
intestine) could be a potential key solution in minimizing Hg contamination in
fish. The related factors involved in intestinal demethylation deserve more
attention in the future.
PMID- 28514846
TI - Natural Mutagenesis-Enabled Global Proteomic Study of Metabolic and Carbon Source
Implications in Mutant Thermoacidophillic Archaeon Sulfolobus solfataricus
PBL2025.
AB - The thermoacidophilic crenarchaeon Sulfolobus solfataricus has been widely used
as a model organism for archaeal systems biology research. Investigation using
its spontaneous mutant PBL2025 provides an effective metabolic baseline to study
subsequent mutagenesis-induced functional process shifts as well as changes in
feedback inhibitions. Here, an untargeted metabolic investigation using
quantitative proteomics and metabolomics was performed to correlate changes in S.
solfataricus strains P2 against PBL2025 and under both glucose and tryptone. The
study is combined with pathway enrichment analysis to identify prominent proteins
with differential stoichiometry. Proteome level quantification reveals that over
20% of the observed overlapping proteome is differentially expressed under these
conditions. Metabolic-induced differential expressions are observed along the
central carbon metabolism, along with 12 other significantly regulated pathways.
Current findings suggest that PBL2025 is able to compensate through the induction
of carbon metabolism, as well as other anabolic pathways such as Val, Leu and iso
Leu biosynthesis. Studying protein abundance changes after changes in carbon
sources also reveals distinct differences in metabolic strategies employed by
both strains, whereby a clear down-regulation of carbohydrate and nucleotide
metabolism is observed for P2, while a mixed response through down-regulation of
energy formation and up-regulation of glycolysis is observed for PBL2025. This
study contributes, to date, the most comprehensive network of changes in
carbohydrate and amino acid pathways using the complementary systems biology
observations at the protein and metabolite levels. Current findings provide a
unique insight into molecular processing changes through natural (spontaneous)
metabolic rewiring, as well as a systems biology understanding of the metabolic
elasticity of thermoacidophiles to environmental carbon source change,
potentially guiding more efficient directed mutagenesis in archaea.
PMID- 28514847
TI - Electric-Field Assisted Assembly of Colloidal Particles into Ordered Nonclose
Packed Arrays.
AB - Nonclose-packed colloidal arrays have many potential applications ranging from
plasmonic sensors, light trapping for photovoltaics, to transparent electrodes.
However, scalable fabrication of those structures remains a challenge. In this
Article, we investigate the robustness of an electric-field assisted approach
systematically. A monolayer of nonclose-packed crystalline array is first created
under a low-frequency alternating-current electric field in solution. We then
apply a sequence of direct-current pulses to fix the particle array onto the
substrate so that it remains intact even after both field removal and solvent
evaporation. Key process parameters such as the alternating-current field
strength, direct-current magnitude, particle concentration, and solvent
evaporation rate that affect both ordering and fixing of colloidal particles have
been studied systematically. We find that direct currents with an intermediate
magnitude induce electrophoretic motion of particles toward the substrate and
facilitate their permanent adhesion on the substrate due to strong van der Waals
attraction. A higher current, however, causes lateral aggregation of particles
arising from electroosmotic flow of solvent and destroys the periodic ordering
between particles. This approach, in principle, can be conveniently adapted into
the continuous convective assembly process, thus making the fabrication of
nonclose-packed colloidal arrays scalable.
PMID- 28514848
TI - Structure and Oxidation of Pyrrole Adducts Formed between Aflatoxin B2a and
Biological Amines.
AB - Aflatoxin B2a has been shown to bind to proteins through a dialdehyde
intermediate under physiological conditions. The proposed structure of this
adduct has been published showing a Schiff base interaction, but adequate
verification using structural elucidation instrumental techniques has not been
performed. In this work, we synthesized the aflatoxin B2a amino acid adduct under
alkaline conditions, and the formation of a new product was determined using high
performance liquid chromatography-time-of-flight mass spectrometry. The resulting
accurate mass was used to generate a novel proposed chemical structure of the
adduct in which the dialdehyde forms a pyrrole ring with primary amines rather
than the previously proposed Schiff base interaction. The pyrrole structure was
confirmed using 1H, 13C, correlation spectroscopy, heteronuclear single quantum
correlation, and heteronuclear multiple bond correlation NMR and tandem mass
spectrometry. Reaction kinetics show that the reaction is overall second order
and that the rate increases as pH increases. Additionally, this study shows for
the first time that aflatoxin B2a dialdehyde forms adducts with
phosphatidylethanolamines and does so through pyrrole ring formation, which makes
it the first aflatoxin-lipid adduct to be structurally identified. Furthermore,
oxidation of the pyrrole adduct produced a product that was 16 m/z heavier. When
the aflatoxin B2a-lysine (epsilon) adduct was oxidized, it gave a product with an
accurate mass, mass fragmentation pattern, and 1H NMR spectrum that match
aflatoxin B1-lysine, which suggest the transformation of the pyrrole ring to a
pyrrolin-2-one ring. These data give new insight into the fate and chemical
properties of biological adducts formed from aflatoxin B2a as well as possible
interferences with known aflatoxin B1 exposure biomarkers.
PMID- 28514850
TI - DNA Dendrimer-Streptavidin Nanocomplex: an Efficient Signal Amplifier for
Construction of Biosensing Platforms.
AB - We develop a DNA dendrimer-streptavidin (SA) nanocomplex as a novel signal
amplifier to create biosensing platforms for disease-related species. The DNA
dendrimer-SA nanocomplex is fabricated by cross-linking the nonlinear
hybridization chain reaction based DNA dendrimer with the SA-coupled linker DNA
and possesses multiple sticky ends, a high molecular weight, and a hyperbranched
nanostructure with large numbers of DNA duplexes. Taking advantage of the DNA
dendrimer-SA nanocomplex and a label-free quartz crystal microbalance (QCM)
technology, we first construct a mass-sensitive QCM biosensing platform for
nucleic acids, which displays high selectivity and sensitivity, with a detection
limit of 0.062 nM KRAS gene fragment. Then we present a fluorescent sensing
strategy toward HeLa cells by functionalizing the DNA dendrimer-SA nanocomplex
using the sgc8 aptamer and the SYBR Green I intercalating dye. The spiked
recoveries of targets in physiological media are greater than 90%, demonstrating
potential application of created biosensing platforms in clinical diagnosis. This
work expands the rule set of designing DNA nanomaterials for development of
biosensing strategies, and provides universal platforms for detecting disease
related species through simply altering the related capture and reporter DNA
sequences.
PMID- 28514851
TI - Blood-Brain Barrier Penetrating Biologic TNF-alpha Inhibitor for Alzheimer's
Disease.
AB - Tumor necrosis factor alpha (TNF-alpha) driven processes are involved at multiple
stages of Alzheimer's disease (AD) pathophysiology and disease progression.
Biologic TNF-alpha inhibitors (TNFIs) are the most potent class of TNFIs but
cannot be developed for AD since these macromolecules do not cross the blood
brain barrier (BBB). A BBB-penetrating TNFI was engineered by the fusion of the
extracellular domain of the type II human TNF receptor (TNFR) to a chimeric
monoclonal antibody (mAb) against the mouse transferrin receptor (TfR),
designated as the cTfRMAb-TNFR fusion protein. The cTfRMAb domain functions as a
molecular Trojan horse, binding to the mouse TfR and ferrying the biologic TNFI
across the BBB via receptor-mediated transcytosis. The aim of the study was to
examine the effect of this BBB-penetrating biologic TNFI in a mouse model of AD.
Six-month-old APPswe, PSEN 1dE9 (APP/PS1) transgenic mice were treated with
saline (n = 13), the cTfRMAb-TNFR fusion protein (n = 12), or etanercept (non-BBB
penetrating biologic TNFI; n = 11) 3 days per week intraperitoneally. After 12
weeks of treatment, recognition memory was assessed using the novel object
recognition task, mice were sacrificed, and brains were assessed for amyloid beta
(Abeta) load, neuroinflammation, BBB damage, and cerebral microhemorrhages. The
cTfRMAb-TNFR fusion protein caused a significant reduction in brain Abeta burden
(both Abeta peptide and plaque), neuroinflammatory marker ICAM-1, and a BBB
disruption marker, parenchymal IgG, and improved recognition memory in the
APP/PS1 mice. Fusion protein treatment resulted in low antidrug-antibody
formation with no signs of either immune reaction or cerebral microhemorrhage
development with chronic 12-week treatment. Chronic treatment with the cTfRMAb
TNFR fusion protein, a BBB-penetrating biologic TNFI, offers therapeutic benefits
by targeting Abeta pathology, neuroinflammation, and BBB-disruption, overall
improving recognition memory in a transgenic mouse model of AD.
PMID- 28514849
TI - Intramolecular Hydrogen Atom Transfer in Aminyl Radical at Room Temperature with
Large Kinetic Isotope Effect.
AB - We report a large kinetic isotope effect at 298 K, kH/kD ~ 150, associated with
an intramolecular 1,5-hydrogen atom transfer (1,5-HAT) in the decay of a
PEGylated carbazyl (aminyl) radical in solution. The experimental observations
surprisingly combine the hallmarks of tunneling, including large KIEs and unusual
activation parameters, with linear Arrhenius and Eyring plots over an
exceptionally wide temperature range of 116 K.
PMID- 28514852
TI - Separated Immobilization of Incompatible Enzymes on Polymer Substrate via Visible
Light Induced Living Photografting Polymerization.
AB - The use of the mixed catalytic system with several enzymes can provide multiple
benefits in terms of the cost, simplification of a multistep reaction, and
effectiveness of complex chemical reactions. Although study of different enzyme
coimmobilization systems has attracted increasing attention in recent years,
separately immobilizing enzymes which can not coexist on one support is still one
of the great challenges. In this paper, a simple and effective strategy was
introduced to separately encapsulate incompatible trypsin and transglutaminase
(TGase) into different poly(ethylene glycol) (PEG) network layer grafted on low
density polyethylene (LDPE) film via visible light induced living photografting
polymerization. As a proof of concept, this dual-enzyme separately loaded film
was used to catalyze the synthesis of a new target antitumor drug LTV
azacytidine. The final results demonstrated that this strategy could maintain
higher activities of both enzymes than the mixed coimmobilization method. And the
mass spectra analysis results demonstrated that LTV-azacytidine was successfully
synthesized. We believe that this facile and mild separately immobilizing
incompatible enzyme strategy has great application potential in the field of
biocatalysis.
PMID- 28514853
TI - Targeting the Central Nervous System (CNS): A Review of Rabies Virus-Targeting
Strategies.
AB - The transport of drugs across the blood-brain barrier is challenging. The use of
peptide sequences derived from viruses with a central nervous system (CNS)
tropism is one elegant option. A prominent example is the rabies virus
glycopeptide-29 (RVG-29), which is said to enable a targeted brain delivery.
Although the entry mechanism of the rabies virus into the CNS is very well
characterized, it is unknown whether RVG-29-functionalized drug delivery systems
(DDSs) follow this pathway. RVG-29-functionalized DDSs present themselves with
modifications of the RVG-29 peptide sequence and different physicochemical
properties compared to the rabies virus. To our surprise, the impact of these
changes on the functionality is completely neglected. This review explores virus
related CNS-targeting strategies by comparing RVG-29-functionalized DDSs with
regard to their peptide modification, physiochemical properties and their
behavior in cell culture studies with a special focus on the original pathway of
rabies virus entry into the CNS.
PMID- 28514854
TI - New Approach for the Synthesis of Nanozirconia Fortified Microcapsules.
AB - Robust poly(urea-formaldehyde) (PUF) microcapsules with composite shells
comprising zirconia (ZrO2) nanopowder incorporated in PUF were fabricated via a
novel and facile one-pot synthesis. ZrO2 nanopowder was chosen because it owns
one of the highest mechanical strengths among ceramics. The nanopowder was
predispersed in the core material to combine encapsulation and fortification into
a single process. In the core, the well-dispersed nanopowder migrated to the
interface, where PUF polymerization took place. The mechanical strength of the
microcapsule with nano-ZrO2 incorporated in the shell (42% by weight) is three
times greater than that of the microcapsule without ZrO2. In a preliminary
application wherein the microcapsules were embedded in a model of poly(vinyl
alcohol) (PVA) membrane, the PVA specimen exhibited a higher ultimate tensile
strength when fortified microcapsules were embedded than when unfortified
microcapsules were used.
PMID- 28514855
TI - Osmotic Stress Induced Desorption of Calcium Ions from Dipolar Lipid Membranes.
AB - The interaction between multivalent ions and lipid membranes with saturated tails
and dipolar (net neutral) headgroups can lead to adsorption of the ions onto the
membrane. The ions charge the membranes and contribute to electrostatic repulsion
between them, in a similar manner to membranes containing charged lipids. Using
solution X-ray scattering and the osmotic stress method, we measured and modeled
the pressure-distance curves between partially charged membranes containing
mixtures of charged (1,2-dilauroyl-sn-glycero-3-phospho-l-serine, DLPS) and
dipolar (1,2-dilauroyl-sn-glycero-3-phosphocholine, DLPC) lipids over a wide
range of membrane charge densities. We then compared these pressure-distance
curves with those of DLPC membranes in the presence of 10 mM CaCl2. Our data and
modeling show that when low osmotic stress is applied to the DLPC bilayers, the
membrane charge density is equivalent to that of a charged membrane containing
ca. 4 mol % DLPS and 96 mol % DLPC. As the osmotic stress increased, the charge
density of the DLPC membrane decreased and resembled that of a membrane
containing ca. 1 mol % DLPS. These data are consistent with desorption of the
calcium ions from the DLPC membrane with increasing osmotic stress.
PMID- 28514857
TI - Pathways for Gold Nucleation and Growth over Protein Cages.
AB - Proteins are widely utilized as templates in biomimetic synthesis of gold
nanocrystals. However, the role of proteins in mediating the pathways for gold
nucleation and growth is not well understood, in part because of the lack of
spatial resolution in probing the complicated biomimetic mineralization process.
Self-assembled protein cages, with larger size and symmetry, can facilitate in
the visualization of both biological and inorganic components. We have utilized
bacteriophage P22 protein cages of ~60 nm diameter for investigating the
nucleation and growth of gold nanocrystals. By adding a gold precursor into the
solution with preexisting protein cages and a reducing agent, gold
nuclei/prenucleation clusters form in solution, which then locate and attach to
specific binding sites on protein cages and further grow to form gold
nanocrystals. By contrast, addition of the reducing agent into the solution with
incubated gold precursor and protein cages leads to the formation of gold
nuclei/prenucleation clusters both in solution and on the surface of protein
cages that then grow into gold nanocrystals. Because of the presence of cysteine
(Cys) with strong gold-binding affinity, gold nanocrystals tend to bind at
specific sites of Cys, irrespective of the binding sites of gold ions. Analyzing
the results obtained using these alternate routes provide important insights into
the pathways of protein-mediated biomimetic nucleation of gold that challenge the
importance of incubation, which is widely utilized in the biotemplated synthesis
of inorganic nanocrystals.
PMID- 28514856
TI - Cell Adhesion on RGD-Displaying Knottins with Varying Numbers of Tryptophan Amino
Acids to Tune the Affinity for Assembly on Cucurbit[8]uril Surfaces.
AB - Cell adhesion is studied on multivalent knottins, displaying RGD ligands with a
high affinity for integrin receptors, that are assembled on CB[8]-methylviologen
modified surfaces. The multivalency in the knottins stems from the number of
tryptophan amino acid moieties, between 0 and 4, that can form a heteroternary
complex with cucurbit[8]uril (CB[8]) and surface-tethered methylviologen (MV2+).
The binding affinity of the knottins with CB[8] and MV2+ surfaces was evaluated
using surface plasmon resonance spectroscopy. Specific binding occurred, and the
affinity increased with the valency of tryptophans on the knottin. Additionally,
increased multilayer formation was observed, attributed to homoternary complex
formation between tryptophan residues of different knottins and CB[8]. Thus, we
were able to control the surface coverage of the knottins by valency and
concentration. Cell experiments with mouse myoblast (C2C12) cells on the self
assembled knottin surfaces showed specific integrin recognition by the RGD
displaying knottins. Moreover, cells were observed to elongate more on the
supramolecular knottin surfaces with a higher valency, and in addition, more
pronounced focal adhesion formation was observed on the higher-valency knottin
surfaces. We attribute this effect to the enhanced coverage and the enhanced
affinity of the knottins in their interaction with the CB[8] surface.
Collectively, these results are promising for the development of biomaterials
including knottins via CB[8] ternary complexes for tunable interactions with
cells.
PMID- 28514858
TI - Cholesterol Based Surface Active Ionic Liquid That Can Form Microemulsions and
Spontaneous Vesicles.
AB - In this article, we have reported the synthesis and physicochemical
characterization of a novel l-glycine amino acid derived cholesterol based
surface active ionic liquid (SAIL). This SAIL has been explored for the
preparation of ionic liquid (IL)-in-oil microemulsions and vesicles. The
formation of IL-in-oil microemulsion is characterized by construction of a
ternary phase diagram, dynamic light scattering (DLS) measurement, proton nuclear
magnetic resonance (1H NMR) study, fluorescence measurement using coumarin 480 (C
480) as a molecular probe, and also by recording the diffusion behavior of the
molecular probe rhodamine 6G (R6G) in microemulsion droplets through the
fluorescence correlation spectroscopy (FCS) technique. Similarly, the spontaneous
vesicle formation from the SAIL in water has been established using DLS,
transmission electron microscopy (TEM), cryogenic-transmission electron
microscopy (cryo-TEM), field emission scanning electron microscopy (FESEM),
atomic force microscopy (AFM), FCS, and fluorescence lifetime imaging microscopy
(FLIM) measurements. These aggregates may potentially serve as good biomimicking
models and possible drug carriers.
PMID- 28514859
TI - What Does "Important New Physical Insights" Mean? Tips for Writing Better Papers.
PMID- 28514860
TI - What Does "Important New Physical Insights" Mean? Tips for Writing Better Papers.
PMID- 28514861
TI - Spotlights: Volume 8, Issue 10.
PMID- 28514862
TI - Importance of Solvation for the Accurate Prediction of Oxygen Reduction
Activities of Pt-Based Electrocatalysts.
PMID- 28514863
TI - Surface dependent contact activation of factor XII and blood plasma coagulation
induced by mixed thiol surfaces.
AB - Studies of the activation of FXII in both platelet poor plasma and in neat buffer
solutions were undertaken for a series of mixed thiol self-assembled monolayers
spanning a broad range of water wettability. A wide spectrum of carboxyl/methyl-,
hydroxyl/methyl-, and amine/methyl-thiol modified surfaces were prepared,
characterized, and then utilized as the procoagulant materials in a series of
FXII activation studies. X-ray photoelectron spectroscopy was utilized to verify
the sample surface's thiol composition and contact angles measured to determine
the sample surface's wettability. These samples were then used in in vitro
coagulation assays using a 50% mixture of recalcified plasma in phosphate
buffered saline. Alternatively, the samples were placed into purified FXII
solutions for 30 min to assess FXII activation in neat buffer solution. Plasma
coagulation studies supported a strong role for anionic surfaces in contact
activation, in line with the traditional models of coagulation, while the
activation results in neat buffer solution demonstrated that FXIIa production is
related to surface wettability with minimum levels of enzyme activation observed
at midrange wettabilities, and no statistically distinguishable differences in
FXII activation seen between highly wettable and highly nonwettable surfaces.
Results demonstrated that the composition of the solution and the surface
properties of the material all contribute to the observation of contact
activation, and the activation of FXII is not specific to anionic surfaces as has
been long believed.
PMID- 28514865
TI - Therapeutic alliance in youth with autism spectrum disorder receiving cognitive
behavioral treatment for anxiety.
AB - Symptoms of autism spectrum disorder may influence alliance in psychotherapy.
This study examined therapeutic alliance and its relationship with child
characteristics and anxiety treatment outcomes in youth with autism spectrum
disorder. Youth ( N = 64) with autism spectrum disorder and co-occurring anxiety
(7-16 years, IQ > 70) received 16 sessions of modular cognitive-behavioral
therapy. Post-treatment therapist, youth and parent ratings of alliance as well
as pre- and post-treatment ratings of child behavior were gathered. Ratings of
alliance were commensurate to ratings seen in children without autism spectrum
disorder. Measures of treatment outcome, but not pretreatment characteristics,
were significantly associated with therapist ratings of alliance strength. Data
suggest that therapeutic alliance may not be impaired in anxious youth with
autism spectrum disorder and may be associated with treatment outcome.
PMID- 28514864
TI - Application of advanced sampling and analysis methods to predict the structure of
adsorbed protein on a material surface.
AB - The use of standard molecular dynamics simulation methods to predict the
interactions of a protein with a material surface have the inherent limitations
of lacking the ability to determine the most likely conformations and
orientations of the adsorbed protein on the surface and to determine the level of
convergence attained by the simulation. In addition, standard mixing rules are
typically applied to combine the nonbonded force field parameters of the solution
and solid phases the system to represent interfacial behavior without validation.
As a means to circumvent these problems, the authors demonstrate the application
of an efficient advanced sampling method (TIGER2A) for the simulation of the
adsorption of hen egg-white lysozyme on a crystalline (110) high-density
polyethylene surface plane. Simulations are conducted to generate a Boltzmann
weighted ensemble of sampled states using force field parameters that were
validated to represent interfacial behavior for this system. The resulting
ensembles of sampled states were then analyzed using an in-house-developed
cluster analysis method to predict the most probable orientations and
conformations of the protein on the surface based on the amount of sampling
performed, from which free energy differences between the adsorbed states were
able to be calculated. In addition, by conducting two independent sets of TIGER2A
simulations combined with cluster analyses, the authors demonstrate a method to
estimate the degree of convergence achieved for a given amount of sampling. The
results from these simulations demonstrate that these methods enable the most
probable orientations and conformations of an adsorbed protein to be predicted
and that the use of our validated interfacial force field parameter set provides
closer agreement to available experimental results compared to using standard
CHARMM force field parameterization to represent molecular behavior at the
interface.
PMID- 28514867
TI - Acute, Temporary, Unilateral Facial Nerve Palsy After Dermatologic Surgery: A
Report of 3 Cases.
AB - Facial nerve dysfunction can be functionally and cosmetically debilitating and is
commonly associated with high anxiety for patients. We report 3 cases of
temporary, unilateral facial nerve palsy following dermatologic surgery under
local anaesthesia over the preauricular cheek and mandibular angle, which, to our
knowledge, has not been reported in the literature. Given its frightening
presentation mimicking a stroke, it is essential for dermatologists to become
aware of this complication to inform their patients more thoroughly. Thus, when
performing facial surgery over these regions, we recommend that dermatologists
include this rare complication and its good prognosis in the consenting process
to minimise anxiety for those who experience it intra- or postoperatively.
PMID- 28514866
TI - Social support and amphetamine-type stimulant use among female sex workers in
China.
AB - BACKGROUND: Existing research has suggested a positive role of social support in
reducing drug use among female sex workers (FSWs). However, there is limited
research on the role of social support in amphetamine-type stimulant (ATS) use
among FSWs in China. This study explored the present situation of ATS use among
FSWs in Guangxi, China and examined the associations of different types of social
support from different sources with ATS use. METHOD: A sample of 1022 FSWs was
recruited from 56 commercial sex venues in Guangxi Autonomous Region in China.
Bivariate comparison was used to compare demographic characteristics and source
of emotional or tangible social support across frequency of ATS use among FSWs.
The relationship between social support and ATS use was examined using multiple
ordinal logistic regression models controlling for the potential confounding
effects of demographic variables. RESULTS: The multiple ordinal logistic
regression indicated that FSWs who were from younger age groups (aOR = 10.88 for
age group <20; aOR = 2.80 for age group 20-23), and from all higher-income venues
(aOR = 1.96 for venue level 1; aOR = 2.28 for venue level 2; aOR = 1.81 for venue
level 3) tended to use ATS more frequently. They also tended to use ATS more
frequently when they depended on their boyfriends (aOR = 1.08) for emotional
support or on their co-workers for tangible support (aOR = 1.17). CONCLUSIONS:
Different types of social support from different sources can be either positively
or negatively associated with ATS use among FSWs, therefore, the future
intervention efforts should differentiate and target different types and
different sources of social support in response to the living and work conditions
of FSWs.
PMID- 28514869
TI - Bullying-related behaviour in adolescents with autism: Links with autism severity
and emotional and behavioural problems.
AB - This study examined the association between peer-reported bullying-related
behaviours (bully, victim, outsider and defender), age, gender, autism severity
and teacher-rated emotional and behavioural problems in adolescents with autism
spectrum disorder, using a multi-informant approach. The sample comprised 120
adolescents (11% girls, Mage = 15.6 years, standard deviation = 1.89 years)
attending a special school for children with autism. Results show that bullying
decreased with age and was associated with behavioural problems, while
victimisation was only associated with peer problems - a pattern of results
comparable to studies exploring these associations in typically developing
children. However, there were few associations among study variables for outsider
or defender behaviours in this sample. Notably, children's autism severity did
not significantly predict bullying-related behaviours.
PMID- 28514868
TI - Phytochemical composition and in vitro screening of the antimicrobial activity of
essential oils on oral pathogenic bacteria.
AB - In this study, the activity of essential oils (EOs) against microorganisms
involved in oral diseases was evaluated. Fourteen EOs were selected and subjected
to gas chromatographic analysis, including Illicium verum, Eucaliptus globulus,
Eugenia caryophyllata, Leptospermum scoparium, Mentha arvensis, Mentha piperita,
Myrtus communis, Salvia officinalis, Melaleuca alternifolia, Rosmarinus
officinalis, Lavandula x intermedia, Thymus capitatus and Thymus vulgaris. These
EOs were tested for their antimicrobial activity on Streptococcus mutans and
Lactobacillus species clinically isolated from dental surgery patients. The
antibacterial activity was evaluated by means of the disc diffusion and the
minimum inhibitory concentration (MIC). Five EOs, having shown an interesting
antimicrobial activity, were selected for a second screening in combination
between them and with chlorhexidine. From the second assays, two EO-EO and three
EO-chlorhexidine associations gave interesting results as potential constituents
of mouthwashes, especially for the contribution of oxygenated monoterpenes,
including menthol, thymol and carvacrol.
PMID- 28514870
TI - Biomarker Profile of Sepsis-Associated Coagulopathy Using Biochip Assay for
Inflammatory Cytokines.
AB - Disseminated intravascular coagulation (DIC) is a major pathophysiological
mechanism of sepsis and greatly increases the risk of death in septic patients.
Disseminated intravascular coagulation is a complex physiological phenomenon that
involves inappropriate activation of coagulation, inflammation, and endothelial
processes. The purpose of this study was to analyze the levels of inflammatory
cytokines in the plasma of patients with DIC in order to compare the measured
levels with those from healthy individuals, draw correlations, and provide a
basis for further biomarker panel development. The inflammatory biomarkers
interleukin (IL) 1beta, IL-6, IL-8, IL-10, interferon (IFN) gamma, vascular
endothelial growth factor (VEGF), tumor necrosis factor (TNF) alpha, monocyte
chemoattractant protein (MCP)-1, and epidermal growth factor (EGF) showed
significant ( P < .05) elevation in patients with DIC. Interestingly, while
numerous correlations were present between IL-beta, IL-6, IL-8, IL-10, IFN-gamma,
TNF-alpha, MCP-1, and many of the inflammatory cytokines measured, VEGF and EGF
exhibited much less extensive correlation, suggesting that their involvement in
DIC may be independent of the other investigated inflammatory markers.
PMID- 28514871
TI - Pulse Wave Velocity: Retrospective Analysis in a Balkan Normotensive and
Hypertensive Population: A Study of 9923 Patients.
AB - We compared pulse wave velocity (PWV) between hypertensive patients and control
patients to identify demographics and patient characteristics related to PWV. We
retrospectively analyzed 9923 participants (3105 controls and 6818 hypertensive
patients) from 5 outpatient hypertensive clinics (in Serbia and Greece). Pulse
wave velocity had different distribution between controls and hypertensive
patients ( P < .001). The magnitude of PWV increase was related to blood pressure
(BP) category (from optimal to stage III hypertension; P < .001). Even in
hypertensive patients with systolic BP (SBP) <140 and/or diastolic BP (DBP) <90
mm Hg, PWV was greater than in control patients ( P < .001). Pulse wave velocity
was associated with almost all baseline characteristics of hypertensive patients
(body mass index [BMI], gender, age, SBP, DBP, smoking status, and heart rate; P
< .001). This association remained after adjustment of PWV confounders. There
were 2231 (32.7%) hypertensive patients who had reached SBP <140 mm Hg and DBP
<90 mm Hg. Pulse wave velocity was increased in hypertensive patients, and the
degree of PWV increase was associated with baseline BP as well as with
anthropometric parameters (eg, BMI, gender, age, heart rate, and smoking status).
PMID- 28514872
TI - Best Medical Treatment for Patients with Carotid Stenosis: Evidence-Based
Medicine or Wishful Thinking?
PMID- 28514873
TI - Unpacking community mobility: a preliminary study into the embodied experiences
of stroke survivors.
AB - PURPOSE: To enrich the discussion on mobility in stroke rehabilitation by
translating theoretical repertoires of mobility from the context of geography to
rehabilitation. METHOD: Qualitative research methodology was applied, and
included in-depth interviews with stroke survivors. RESULTS: This study revealed:
(a) social and material differences in clinical, private and public places; (b)
ambivalences and shifting tensions in bodily, family and community life; (c)
differences in access to resources to be used for mobility. Moving around safely
was not a matter of being physically able to walk independently, it also involved
dealing with different human actors - such as children, partners and shoppers,
and non-human actors - such as doorbells and traffic rules. Stroke survivors had
to balance exercise and training, family and working life, and leisure and
pleasure, and to renegotiate their mobility in each context. CONCLUSIONS: Our
study showed that mobility has many aspects that interact with each other in
multiple ways for stroke survivors when they return home and thereafter. The
current focus on adherence to mobility and exercise training at home needs to be
critically reviewed as it does not capture the multiplicities embodied in real
life settings. Implications for rehabilitation Rehabilitation medicine needs to
consider mobility as a way to connect places that are meaningful to individuals
rather than as movements from A to B. Clinical outcome measurement tools, such as
the 10-meter walk test, are inadequate for evaluating participation in the
mobility domain at home or in the community. Mobility issues at the participation
domain need to be considered in "how they hang together" rather than
distinguished in different disciplinary domains. Rehabilitation practitioners
should teach stroke survivors concrete strategies on how to creatively deal with
the ambivalences and tensions around mobility in home and community life.
PMID- 28514874
TI - Oncolytic Recombinant Vesicular Stomatitis Virus (VSV) Is Nonpathogenic and
Nontransmissible in Pigs, a Natural Host of VSV.
AB - Vesicular stomatitis virus (VSV) is a negative-stranded RNA virus that naturally
causes disease in livestock including horses, cattle and pigs. The two main
identified VSV serotypes are New Jersey (VSNJV) and Indiana (VSIV). VSV is a
rapidly replicating, potently immunogenic virus that has been engineered to
develop novel oncolytic therapies for cancer treatment. Swine are a natural host
for VSV and provide a relevant and well-established model, amenable to biological
sampling to monitor virus shedding and neutralizing antibodies. Previous reports
have documented the pathogenicity and transmissibility of wild-type isolates and
recombinant strains of VSIV and VSNJV using the swine model. Oncolytic VSV
engineered to express interferon-beta (IFNbeta) and the sodium iodide symporter
(NIS), VSV-IFNbeta-NIS, has been shown to be a potent new therapeutic agent
inducing rapid and durable tumor remission following systemic therapy in
preclinical mouse models. VSV-IFNbeta-NIS is currently undergoing clinical
evaluation for the treatment of advanced cancer in human and canine patients. To
support clinical studies and comprehensively assess the risk of transmission to
susceptible species, we tested the pathogenicity and transmissibility of
oncolytic VSV-IFNbeta-NIS using the swine model. Following previously established
protocols to evaluate VSV pathogenicity, intradermal inoculation with 107 TCID50
VSV-IFNbeta-NIS caused no observable symptoms in pigs. There was no detectable
shedding of infectious virus in VSV-IFNbeta-NIS in biological excreta of
inoculated pigs or exposed naive pigs kept in direct contact throughout the
experiment. VSV-IFNbeta-NIS inoculated pigs became seropositive for VSV
antibodies, while contact pigs displayed no symptoms of VSV infection, and
importantly did not seroconvert. These data indicate that oncolytic VSV is both
nonpathogenic and not transmissible in pigs, a natural host. These findings
support further clinical development of oncolytic VSV-IFNbeta-NIS as a safe
therapeutic for human and canine cancer.
PMID- 28514875
TI - Identification of novel Nicotinamide Phosphoribosyltransferase (NAMPT) inhibitors
using computational approaches.
AB - Nicotinamide Phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme in the
biosynthesis of NAD. Cancer cells have elevated poly [ADP-Ribose] polymerase 1
(PARP) activity as well as the immense necessity of ATP: thereby consuming NAD at
a higher rate than normal tissues. The perturbation of these intracellular
processes is more sensitive and highly dependent on NAMPT to maintain the
required NAD levels. Functional inhibition of NAMPT is, therefore, a promising
drug target in therapeutic oncology. In this study, the importance of
intermolecular contacts was realized based on contact occupancy and favorable
energetic from molecular dynamic simulation to discern non-critical contacts of
four different classes of potential NAMPT inhibitor bound complexes. Further,
pharmacophore modeling, molecular docking, a quantum mechanical properties and MD
simulation, as well as active site residual network communication were employed
to identify potential leads. Present studies identified two leads, 2 and 3 which
have better binding free energy compared to known inhibitors and showed stable
hydrogen bonding and hydrophobic contacts with beta barrel cavity lining residues
in the active site of the dimer interface (A'B). Lead 2 containing fluorene as
central core and lead 3 having phenyl-benzamide as a core showed stable moiety
which was observed from electronic property analysis. Active site residual
communication in identified leads bound complex also showed similarity to known
inhibitor complexes. Compounds containing these moieties were not reported until
now against NAMPT inhibition and can be considered as novel cores for future
development of drugs to inhibit NAMPT function.
PMID- 28514876
TI - Potential support ratios: Cohort versus period perspectives.
AB - The 'prospective potential support ratio' has been proposed by researchers as a
measure that accurately quantifies the burden of ageing, by identifying the
fraction of a population that has passed a certain measure of longevity, for
example, 17 years of life expectancy. Nevertheless, the prospective potential
support ratio usually focuses on the current mortality schedule, or period life
expectancy. Instead, in this paper we look at the actual mortality experienced by
cohorts in a population, using cohort life tables. We analyse differences between
the two perspectives using mortality models, historical data, and forecasted
data. Cohort life expectancy takes future mortality improvements into account,
unlike period life expectancy, leading to a higher prospective potential support
ratio. Our results indicate that using cohort instead of period life expectancy
returns around 0.5 extra younger people per older person among the analysed
countries. We discuss the policy implications implied by our cohort measures.
PMID- 28514877
TI - The assumptions of cognitive neuropsychology: Reflections on Caramazza (1984,
1986).
AB - Approximately 30 years ago, Caramazza (1984. The logic of neuropsychological
research and the problem of patient classification in aphasia. Brain and
Language, 21, 9-20; 1986. On drawing inferences about the structure of normal
cognitive systems from the analysis of patterns of impaired performance. Brain
and Language, 5, 41-66) proposed that cognitive neuropsychology needs to make
four assumptions in order for its inferences from pathological performance to the
structure of intact cognitive systems to be justifiable. These assumptions were:
fractionation, modularity, transparency and universality. Analysis of the current
status of these assumptions leads me to conclude that all four remain defensible
today.
PMID- 28514878
TI - Anticoagulant cessation following atrial fibrillation ablation: limits of the ECG
guided approach.
AB - INTRODUCTION: Long-term cessation of oral anticoagulation (OAC) following
successful catheter or surgical ablation of atrial fibrillation (AF) is debated.
Usually, in the presence of sinus rhythm at serial ECG recordings, the CHADS2,
CHA2DS2VASc, and HAS-BLED scores are adopted to guide decision regarding OAC
management. Areas covered: The safety of OAC cessation in patients without
recurrent AF but with historically elevated risk for thromboembolism remains
largely unknown. Taking the cue from two clinical cases, we provide an updated
summary of the latest evidence regarding how to manage OAC after a successful
atrial fibrillation ablation. Expert commentary: The present clinical perspective
suggests that, at least within patients with severely enlarged left atrium,
previous cardiac surgery and catheter or surgical AF ablation, especially if
repeated, assessment of atrial contractility by transthoracic echocardiography
should be performed before discontinuing OAC in patients who maintain sinus
rhythm, confirmed by serial ECG or Holter monitorings.
PMID- 28514879
TI - Growth restriction: identifying fetuses at risk.
AB - PURPOSE: Examine risks of intrauterine growth restriction (IUGR) and composite
perinatal outcomes with estimated fetal weights (EFW) 10-20th%, and compare
outcomes using umbilical artery Doppler (UAD). MATERIALS AND METHODS:
Retrospective, cohort evaluating ultrasound (US) EFW 10-20th%, between 2002 and
2012. Cases were identified with EFW % 10-20. Controls, EFW >20th% were obtained
for each case, matched by gestational age, and US date. Unadjusted and adjusted
logistic regression was used for outcomes. RESULTS: Seven hundred and sixty-seven
cases met criteria with matched controls. Fetuses having EFW 10-20th% (GA 33.6 +/
3.7 weeks) had increased IUGR on follow up ultrasound (OR 26.5[10.2-68.7], p <
.01), small for gestational age (SGA) (OR 9.2 [6.9-12.3], p < .01), neonatal
intensive care unit (NICU) admissions (OR 2.4 [1.6-3.6], p < .01), and composite
perinatal morbidity (OR 7.8 [6.0-10.1], p < .01) on adjusted analyses. Abnormal
UAD in cases had greater rates of 5 min Apgar <7, NICU admission and composite
morbidity (p < .05). CONCLUSIONS: Pregnancies with EFW 10-20th% at the time of
initial US are at increased risk for developing IUGR and being SGA at birth, with
more NICU admissions and composite perinatal outcomes; abnormal UAD evaluation in
cases conveyed further increase in outcomes.
PMID- 28514880
TI - The uterocervical angle and its relationship with preterm birth.
AB - OBJECTIVES: The objective of this study is to determine whether the uterocervical
angle (UCA) correlates with the risk of spontaneous preterm birth (sPTB) < 34
weeks and assess its interobserver variability. STUDY DESIGN: Case-control study
of 275 women including 34 who started labor spontaneously and gave birth before
34 weeks of gestation (preterm group) and 241 who gave birth at term (control
group). Images used to report cervical length were re-measured for UCA. RESULTS:
Mean UCA in the second trimester was wider in the preterm group (105.16 degrees )
compared with the control group (94.53 degrees ), p = .015. The intraclass
correlation coefficient was 0.821 (95% CI: 0.74-0.97) for masked interobserver
variability, which implies correct agreement among UCA measurements. Mean UCA
increased from the first to the second trimester (84.2 degrees versus 94.5
degrees ; p = .019). CONCLUSIONS: Wider UCA in the second trimester is related to
sPTB. UCA measurement is a reproducible technique. UCA appears to increase from
the first to the second trimester. Prospective studies, with ultrasound
examinations aimed at measuring UCA in vivo, are needed to accurately assess the
characteristics of this marker and its potential as a predictor of sPTB in
clinical practice.
PMID- 28514882
TI - Interventions in pain management for persons with an intellectual disability.
AB - Pain is a multidimensional and subjective experience, and an ideal pain
management regime needs to be comprehensive, integrative and involve all relevant
persons. Multimodal interventions may include pharmacological, physical, social,
psychological and spiritual approaches in order to address pain management at a
molecular, functional, behavioural, cognitive and affective levels. Pain
management interventions will vary according to pain aetiology, patient
characteristics and preferences. In keeping with best practice guidelines for
effective pain management, a structured approach incorporating an effective
assessment of pain by the healthcare professional, identification of the source
and type of pain and accurate documentation is essential. This article focuses on
pharmacological and non-pharmacological pain management for individuals with
intellectual disability.
PMID- 28514881
TI - Trisomy 13 and the risk of gestational hypertensive disorders: a population-based
study.
AB - PURPOSE: To describe the rate and severity of gestational hypertensive disorders
(GHDs) in pregnancies complicated by trisomy 13 (T13). MATERIALS AND METHODS:
Retrospective cohort study of singleton deliveries in California from 2005 to
2008 using vital statistics and ICD-9 data. We were interested in gestational
hypertension (gHTN), preeclampsia with and without severe features (sPREX and
PREX), and gestational age at delivery. Pregnancies and maternal complications
affected by prenatally diagnosed T13 were compared to unaffected pregnancies.
Regression models were used to compute adjusted odds ratios for pregnancy
outcomes by T13 status. RESULTS: Of the 2,029,004 deliveries, 142 women had
prenatally diagnosed T13. A diagnosis of GHD occurred in 26.8% of the T13
pregnancies versus 6% of the non-T13 pregnancies (p < .001). This remained true
for gHTN (9.2% versus 3.2%, p=.001), PREX (12% versus 2.2%, p < .001), and sPREX
(8.5% versus 0.9%, p < .001). After adjusting for confounders, T13 pregnancies
were 6.3-times more likely to be affected by GHD, and 12.5-times more likely to
have sPREX. Delivery <37 and <32 weeks in the setting of GHD was 14.1-times and
11.2-times likely among women with T13. CONCLUSIONS: Women with T13 pregnancies
were significantly more likely to have gHTN, preeclampsia, sPREX, and to deliver
<32 weeks.
PMID- 28514883
TI - Bioethical analysis to the therapeutic use of Cannabis: Integrative review.
AB - INTRODUCTION: Despite being considered as a contravention under some countries'
legislation, the therapeutic use of Cannabis sativa has been growing in Brazil,
due to the promising results observed in many pathologies. Such a scenario has
fostered the need to deepen discussions on the subject and possibly revise
legislation governing the substance use and access. OBJECTIVES: Identify the
types of stigma related to the therapeutic use of Cannabis and describe the
strategies people use to overcome stigma. METHODS: This integrative review was
carried out in the databases PubMed, Scopus, CINAHL, MEDLINE, PsycINFO, Web of
Science, and Cochrane Library, with 565 articles being retrieved. Triads' cross
check were done, first maintaining the "cannabis" and "therapeutic use" pair,
added by "stigma," "bioethics," "ethics," "social consequences," and "legal
consequences." The final selection resulted in six articles. Ethical
Consideration: However, the ethical issues that pervade and regulate decisions on
this subject must be considered. RESULTS: Different dimensions and types of
stigma related to the therapeutic use of Cannabis have been identified. The
bioethical principle of autonomy was an expression of citizenship and human
rights, mitigating internal conflicts related to self-stigma and the effects of
external stigma on the person's life. CONCLUSION: It was possible to identify the
types of stigma related to the therapeutic use of Cannabis is an internal
dimension represented (self-stigma) and an external dimension, represented
(social and structural stigmas) and to identify strategies adopted to face this
stigma: skills training group for users, elaboration of laws and specific
programs to clarify the therapeutic use of Cannabis with a greater social scope,
and support for family members. Thus, contributing to the building of people's
autonomy in a broader context of decision-making autonomy and executive autonomy
will provide the development of people's capacity to perform complex tasks of
self-management and, consequently, to continue promoting and preserving their
decision-making process and their capacity to plan and perform tasks associated
with managing their lives and their treatments.
PMID- 28514884
TI - The association of placenta previa and assisted reproductive techniques: a meta
analysis.
AB - BACKGROUND: Several epidemiological studies have determined that assisted
reproductive techniques (ART) can increase the risk of placenta previa. To date,
only a meta-analysis has been performed for assessing the relationship between
placenta previa and ART. This meta-analysis was conducted to estimate the
association between placenta previa and ART in singleton and twin pregnancies.
METHODS: A literature search was performed in major databases PubMed, Web of
Science, and Scopus from the earliest possible year to April 2017. The
heterogeneity across studies was explored by Q-test and I2 statistic. The
publication bias was assessed using Begg's and Egger's tests. The results were
reported using odds ratio (OR) and relative risk (RR) estimates with its 95%
confidence intervals (CI) using a random-effects model. RESULTS: The literature
search yielded 1529 publications until September 2016 with 1,388,592
participants. The overall estimate of OR was 2.67 (95%CI: 2.01, 3.34) and RR was
3.62 (95%CI: 0.21, 7.03) based on singleton pregnancies. The overall estimate of
OR was 1.50 (95%CI: 1.26, 1.74) based on twin pregnancies. CONCLUSIONS: We showed
based on odds ratio reports in observational studies that ART procedures are a
risk factor for placenta previa.
PMID- 28514886
TI - Physiological effects of prebiotics and its role in prevention of necrotizing
enterocolitis in preterm neonates.
AB - Necrotizing enterocolitis (NEC) is one of the most serious gastrointestinal
emergencies in very low birth weight (VLBW) preterm neonates, affecting 7-14% of
these neonates. Due to the seriousness of the disease, prevention of NEC is the
most important goal. Current evidence from systematic review and meta-analysis
revealed that probiotics are the most promising intervention in reduction of the
incidence of NEC in VLBW neonates. As per the evidence, prebiotics modulate the
composition of human intestine microflora to the benefit of the host by
suppression of colonization of harmful microorganism and/or the stimulation of
bifidobacterial growth, decreased stool viscosity, reduced gastrointestinal
transit time, and better feed tolerance. Prebiotics may be potential alternatives
or adjunctive therapies to probiotics, despite a lack of evidence supporting its
clinical efficacy in prevention of NEC. In this article, we discuss evidence
based physiological effects of prebiotics and its therapeutic role in prevention
of NEC.
PMID- 28514885
TI - Poorer maternal diet quality and increased birth weight.
AB - OBJECTIVE: Maternal diet and gestational weight gain (GWG) influence birth weight
and infant adiposity, which are important predictors of lifetime health. To
better understand these relationships, we studied associations between maternal
diet and GWG, adiposity, and birth weight in a well characterized cohort of
pregnant women. STUDY DESIGN: Data were obtained from 41 term (>37 weeks),
uncomplicated, singleton pregnancies according to pre-pregnancy BMI categories of
normal (n = 11), overweight (n = 15), or obese (n = 15). Daily consumption of
protein, fat, and carbohydrates and a Healthy Eating Index (HEI-2010) score were
determined from 24 h food recall collections. Associations were modeled using
multinomial logistic and linear regression. RESULTS: Neither the third trimester
maternal diet quality nor the macronutrient consumption was associated with GWG
after adjusting for pre-pregnancy BMI, maternal age, and parity. A ten-point
lower HEI-2010 score was associated with 200 g higher infant birth weight and a
1.0 cm longer length. However, maternal HEI-2010 and macronutrient composition
were unrelated to infant percent body fat, ponderal index, or abdominal
circumference. CONCLUSIONS: Poorer third trimester maternal diet quality was
associated with higher birth weight and longer length, but was unrelated to
markers of infant adiposity. GWG was independent of third trimester maternal diet
composition and quality.
PMID- 28514887
TI - Transanal Inspection and Management of Low Colorectal Anastomosis Performed With
a New Technique: the TICRANT Study.
AB - BACKGROUND: Anastomotic leakage is one of the most serious complications after
rectal cancer surgery. METHOD: A prospective multicenter interventional study to
assess a newly described technique of creating the colorectal and coloanal
anastomosis. The primary outcome was to access the safety and efficacy of this
technique in the reduction of anastomotic leak. RESULT: Fifty-three patients with
rectal cancer who underwent low or ultra-low anterior resection were included in
the study. There were 35 males and 18 females, with a median age of 68 years
(range = 49-89 years). The median tumor distance from the anal verge was 8 cm
(range = 4-12 cm), and the median body mass index was 24 kg/m2 (range = 20-35
kg/m2). Thirty patients underwent open, 16 laparoscopic, and 7 robotic surgeries.
Multiple firing (2-charges) was required in 30 patients to obtain a complete
rectal division. Forty-five patients had colorectal anastomosis, and 8 patients
had coloanal anastomosis. The protective ileostomy was created in 40 patients at
the time of initial surgery. There was no mortality in the first 30 days
postoperatively, and only 10 (19%) patients developed complications. There were 3
anastomotic leakages (6%); 2 of them were subclinical with ileostomy created at
initial operation and both were treated conservatively with transanal drainage
and intravenous antibiotics. One patient required reoperation and ileostomy. The
median length of hospital stay was 10 days (range = 4-20 days). CONCLUSION: Our
technique is a safe and efficient method of creation of colorectal anastomosis.
It is also a universal method that can be used in open, laparoscopic, and robotic
surgeries.
PMID- 28514888
TI - Seeing is believing - healthcare professionals' perceptions of a complex
intervention to improve care towards the end of life: A qualitative interview
study.
AB - BACKGROUND: Methods to improve care, trust and communication are important in
acute hospitals. Complex interventions aimed at improving care of patients
approaching the end of life are increasingly common. While evaluating outcomes of
complex interventions is essential, exploring healthcare professionals'
perceptions is also required to understand how they are interpreted; this can
inform training, education and implementation strategies to ensure fidelity and
consistency in use. AIM: To explore healthcare professionals' perceptions of
using a complex intervention (AMBER care bundle) to improve care for people
approaching the end of life and their understandings of its purpose within
clinical practice. DESIGN: Qualitative study of healthcare professionals.
Analysis informed by Medical Research Council guidance for process evaluations.
SETTING/PARTICIPANTS: A total of 20 healthcare professionals (12 nursing and 8
medical) interviewed from three London tertiary National Health Service
hospitals. Healthcare professionals recruited from palliative care, oncology,
stroke, health and ageing, medicine, neurology and renal/endocrine services.
RESULTS: Three views emerged regarding the purpose of a complex intervention
towards the end of life: labelling/categorising patients, tool to change care
delivery and serving symbolic purpose indirectly affecting behaviours of
individuals and teams. All impact upon potential utility of the intervention.
Participants described the importance of training and education alongside
implementation of the intervention. However, adequate exposure to the
intervention was essential to witness its potential added value or embed it into
practice. CONCLUSION: Understanding differing interpretations of complex
interventions is essential. Consideration of ward composition, casemix and
potential exposure to the intervention is critical for their successful
implementation.
PMID- 28514889
TI - Pain perception in NICU: a pilot questionnaire.
AB - PURPOSE: Neonatal pain management has made a great step forward over the last
several years. Despite the drafting of International guidelines, an under
treatment of neonatal pain is still reported. MATERIALS AND METHODS: Medical and
paramedical personnel working in five Italian NICUs were asked to complete a
questionnaire about pain management. The questionnaire was comprised of three
sections: (i) brief explanation of the purpose; (ii) demographic information,
including age, profession, religious beliefs, and hospital level; (iii)
questionnaire about pain management and prevention. RESULTS: One-hundred and
forty caregivers participated in this study. Non-pharmacological analgesia during
heel prick or venipuncture was used by 64% and 60% of them, respectively; topical
analgesia was performed in 13% of venipunctures; no analgesia was used in 30% of
cases for both heel prick and venipuncture. In the case of lumbar puncture, 35%
of participants used topical analgesia, 15% non-pharmacological approach, 10%
opioids, and 6% intravenous paracetamol. While 65% of participants gave a score
of 4 out of 5 about the importance of pain treatment, 39% of them reported that
in their department no pain scales were used. CONCLUSIONS: Pain treatment in
these NICUs is still far to be optimal. This nonetheless reflects a worldwide
trend, which requires more attention on pain prevention, assessment, and
treatment.
PMID- 28514891
TI - Synergistic Effect of Rapamycin and Metformin Against Age-Dependent Oxidative
Stress in Rat Erythrocytes.
AB - Erythrocytes are particularly vulnerable toward age-dependent oxidative stress
mediated damage. Caloric restriction mimetics (CRMs) may provide a novel strategy
for the maintenance of redox balance as well as effective treatment of age
associated diseases. Herein, we have investigated the beneficial effect of
cotreatment with CRM-candidate drugs, rapamycin (an immunosuppressant drug and
inhibitor of mammalian target of rapamycin) and metformin (an antidiabetic
biguanide and activator of adenosine monophosphate kinase), against aging-induced
oxidative stress in erythrocytes and plasma of aging rats. Male Wistar rats of
age 4 (young) and 24 months (old) were coexposed to rapamycin (0.5 mg/kg body
weight [b.w.]) and metformin (300 mg/kg b.w.), and data were compared with the
response of rats receiving an independent exposure to these chemicals at similar
doses. The exposure of individual candidate drugs significantly reversed the age
dependent alterations in the endpoints associated with oxidative stress such as
reactive oxygen species, ferric reducing ability of plasma, malondialdehyde,
reduced glutathione, plasma membrane redox system, plasma protein carbonyl, and
acetyl cholinesterase in erythrocytes and plasma of aging rats. However, the
cotreatment with rapamycin and metformin showed a significant augmented effect
compared with individual drug interventions on reversal of these age-dependent
biomarkers of oxidative stress, suggesting a synergistic response. Thus, the
findings open up further possibilities for the design of new combinatorial
therapies to prevent oxidative stress- and age-associated health problems.
PMID- 28514890
TI - Spatial recognition test: A novel cognition task for assessing topographical
memory in mice.
AB - Dysfunction in topographical memory is a core feature of several neurological
disorders. There is a large unmet medical need to address learning and memory
deficits as a whole in central nervous system disease. There are considerable
efforts to identify pro-cognitive compounds but current methods are either
lengthy or labour intensive. Our test used a two chamber apparatus and is based
on the preference of rodents to explore novel environments. It was used firstly
to assess topographical memory in mice at different retention intervals (RI) and
secondly to investigate the effect of three drugs reported to be beneficial for
cognitive decline associated with Alzheimer's disease, namely: donepezil,
memantine and levetiracetam. Animals show good memory performance at all RIs
tested under four hours. At the four-hour RI, animals show a significantly poorer
memory performance which can be rescued using donepezil, memantine and
levetiracetam. Using this test we established and validated a spatial recognition
paradigm to address topographical memory in mice by showing a decremental time
induced forgetting response and reversing this decrease in performance using
pharmacological tools. The spatial recognition test differs from more commonly
used visuospatial laboratory tests in both throughput capability and potentially
neuroanatomical substrate. This test has the potential to be used to assess
cognitive performance in transgenic animals, disease models and to screen
putative cognitive enhancers or depressors.
PMID- 28514892
TI - Single-case cognitive neuropsychology in the age of big data.
AB - Historically, single-case studies of brain-damaged individuals have contributed
substantially to our understanding of cognitive processes. However, the role of
single-case cognitive neuropsychology has diminished with the proliferation of
techniques that measure neural activity in humans. Instead, large-scale
informatics approaches in which data are gathered from hundreds of neuroimaging
studies have become popular. It has been claimed that utilizing these informatics
approaches can address problems found in single imaging studies. We first discuss
reasons for why cognitive neuropsychology is thought to be in decline. Next, we
note how these informatics approaches, while having benefits, are not
particularly suited for understanding functional architectures. We propose that
the single-case cognitive neuropsychological approach, which is focused on
developing models of cognitive processing, addresses several of the weaknesses
inherent in informatics approaches. Furthermore, we discuss how using neural data
from brain-damaged individuals provides data that can inform both cognitive and
neural models of cognitive processing.
PMID- 28514893
TI - Cytocompatible polyion complex gel of poly(Pro-Hyp-Gly) for simultaneous rat bone
marrow stromal cell encapsulation.
AB - Polyion complex (PIC) gel of poly(Pro-Hyp-Gly) was successfully fabricated by
simply mixing polyanion and polycation derivatives of poly(Pro-Hyp-Gly), a
collagen-like polypeptide. The polyanion, succinylated poly(Pro-Hyp-Gly), and the
polycation, arginylated poly(Pro-Hyp-Gly), contain carboxy (pKa = 5.2) and
guanidinium (pKa = 12.4) groups, respectively. Mixing the polyanion and the
polycation at physiological pH (pH = 7.4) resulted in PIC gel. The hydrogel
formation was optimum at an equimolar ratio of carboxy to guanidinium groups,
suggesting that ionic interaction is the main determinant for the hydrogel
formation. The hydrogel was successfully used for simultaneous rat bone marrow
stromal cell encapsulation. The encapsulated cells survived and proliferated
within the hydrogel. In addition, the cells exhibited different morphology in the
hydrogel compared with cells cultured on a tissue culture dish as a two
dimensional (2D) control. At day one, a round morphology and homogeneous single
cell distribution were observed in the hydrogel. In contrast, the cells spread
and formed a fibroblast-like morphology on the 2D control. After three days, the
cells in the hydrogel maintained their morphology and some of them formed
multicellular aggregates, which is similar to cell morphology in an in vivo
microenvironment. These results suggest that the PIC gel of poly(Pro-Hyp-Gly) can
serve as a cytocompatible three-dimensional scaffold for stem cell encapsulation,
supporting their viability, proliferation, and in vivo-like behavior.
PMID- 28514894
TI - Successful Repair of Acute Type B and Retrograde Type A Aortic Dissection With
Kidney Ischemia.
AB - Acute dissection of thoracic aorta carries a risk of renal ischemia followed by
the development of a kidney failure. The optimal surgical and nonsurgical
management of these patients, timing of intervention, and the factors predicting
renal recovery are not well delineated and remain controversial. We present a
case of acute type B thoracic aortic dissection with left kidney ischemia.
Evaluation of renal function was performed by the means of internationally
accepted Risk, Injury, Failure, Loss of kidney function, End stage kidney disease
and Acute Kidney Injury Network classifications for acute kidney injury, renal
duplex sonography, and intravascular ultrasound that demonstrated left renal
artery dissection with a flap completely compressing the true lumen. The patient
underwent thoracic endovascular aortic repair and left renal artery stent and
recovered well. Six months later, at the follow-up visit, retrograde type A
aortic dissection was found, which was successfully repaired. Reversal of renal
ischemia after aortic dissection depends on the precise assessment of renal
function and prompt intervention.
PMID- 28514895
TI - Outcomes After Use of Aortouniiliac Endoprosthesis Versus Modular or Unibody
Bifurcated Endoprostheses for Endovascular Repair of Ruptured Abdominal Aortic
Aneurysms.
AB - OBJECTIVES: Outcomes after endovascular repair (EVAR) of ruptured abdominal
aortic aneurysms (rAAAs) have been widely published. There is, however,
controversy on the role of the use of aortouniiliac endoprosthesis (AUI) versus
modular or unibody bifurcated endoprosthesis (MUB) for repair of rAAAs. We study
and compare 30-day outcomes after use of AUI and MUB for all rAAAs focusing
specifically on patients with instability. MATERIALS AND METHODS: Patients who
underwent EVAR for rAAA (n = 425) using AUI (n = 55; 12.9%) and MUB (n = 370;
87.1%) were identified from the American College of Surgeons' National Surgical
Quality Improvement Program (2005-2010) database. Univariable and multivariable
logistic regression analyses were performed. RESULTS: No significant difference (
P > .5) was seen in comorbidities between patients who underwent EVAR with AUI or
MUB; there was also no change in endoprosthesis use from 2005 to 2010 ( P = .7).
Patients who underwent EVAR with AUI more commonly had a history of peripheral
arterial procedure (10.9% vs 4.6%; P = .053) and preoperative transfusion of >4 U
packed red blood cells (18.2% vs 6.8%; P = .004). Use of AUI versus MUB was
associated with more 30-day wound complications (16.4% vs 6.2%; P = .01), return
to operating room (38.2% vs 20.0%; P = .003), and mortality (34.5% vs 21.4%; P =
.03). On multivariable analysis, use of AUI was associated with an increased risk
of 30-day mortality (odds ratio: 2.4; 95% confidence interval: 1.1-5.3). On
subanalysis of the cohort for only the patients with unstable rAAA (n = 159; AUI
= 29 and MUB = 130), 30-day mortality for AUI versus MUB was still higher but not
statistically significant (44.8% vs 32.3%; P = .2). CONCLUSION: Endovascular
repair for ruptured AAA using aortouniliac endoprosthesis is associated with
higher 30-day mortality than using modular or unibody bifurcated endoprosthesis.
PMID- 28514896
TI - "Snare-Ride": A Bailout Technique to Catheterize Target Vessels With Unfriendly
Anatomy in Branched Endovascular Aortic Repair.
AB - PURPOSE: To describe a novel endovascular bailout technique for successful
completion of target vessel stenting during branched stent-graft repair of
thoracoabdominal aortic aneurysms (TAAA) after encountering difficulties with
standard catheterization techniques. TECHNIQUE: Technical difficulties when using
fenestrated and branched grafts should be expected, especially in difficult
anatomy or when an off-the-shelf device (eg, standard 4-branch device) is used
that does not perfectly "match" the anatomy. The "snare-ride technique"
facilitates antegrade transaxillary side branch catheterization and stent
placement during TAAA branched grafting using a snare via a transfemoral
approach. The branch of the graft is catheterized from an axillary access. The
respective target vessel is then catheterized via a femoral access. An Indy snare
is advanced over the transfemoral wire and positioned near the entrance of the
target vessel. The transaxillary wire inside the branch of the graft is then
advanced, snared, and pushed inside the target vessel with the snare. The
procedure is thereafter continued with antegrade bridging of the target vessel in
routine fashion. CONCLUSION: The snare-ride technique can be a useful maneuver to
catheterize target vessels with difficult anatomy in TAAA branched stent-graft
repair. Early experience shows safety and feasibility.
PMID- 28514897
TI - Biomaterials and Bioactive Agents in Spinal Fusion.
AB - Management of degenerative spine pathologies frequently leads to the need for
spinal fusion (SF), where bone growth is induced toward stabilization of the
interventioned spine. Autologous bone graft (ABG) remains the gold-standard
inducer, whereas new bone graft substitutes attempt to achieve effective de novo
bone formation and solid fusion. Limited fusion outcomes have driven motivation
for more sophisticated and multidisciplinary solutions, involving new
biomaterials and/or biologics, through innovative delivery platforms. The present
review will analyze the most recent body of literature that is focused on new
approaches for consistent bone fusion of spinal vertebrae, including the
development of new biomaterials that pursue physical and chemical aptitudes; the
delivery of growth factors (GF) to accelerate new bone formation; and the use of
cells to improve functional bone development. Bone graft substitutes currently in
clinical practice, such as demineralized bone matrix and ceramics, are still used
as a starting point for the study of new bioactive agents. Polyesters such as
polycaprolactone and polylactic acid arise as platforms for the development of
composites, where a mineral element and cell/GF constitute the delivery system.
Exciting fusion outcomes were obtained in several small and large animal models
with these. On what regards bioactive agents, mesenchymal stem cells,
preferentially derived from the bone marrow or adipose tissue, were studied in
this context. Autologous and allogeneic approaches, as well as osteogenically
differentiated cells, have been tested. These cell sources have further been
genetically engineered for specific GF expression. Nevertheless, results on
fusion efficacy with cells have been inconsistent. On the other hand, the
delivery of GF (most commonly bone morphogenetic protein-2 [BMP-2]) has provided
favorable outcomes. Complications related to burst release and dosing are still
the target of research through the development of controlled release systems or
alternative GF such as Nel-like molecule-1 (NELL-1), Oxysterols, or COMP-Ang1.
Promising solutions with new biomaterial and GF compositions are becoming closer
to the human patient, as these evidence high-fusion performance, while offering
cost and safety advantages. The use of cells has not yet proved solid benefits,
whereas a further understanding of cell behavior remains a challenge.
PMID- 28514899
TI - Clinical Positioning Accuracy for Multisession Stereotactic Radiotherapy With the
Gamma Knife Perfexion.
AB - Multisession stereotactic radiation therapy is increasingly being seen as a
preferred option for intracranial diseases in close proximity to critical
structures and for larger target volumes. The objective of this study is to
investigate the reproducibility of the Extend system from Elekta. A retrospective
review was conducted for all patients treated with multisession Gamma Knife
between July 2010 and June 2015, including both malignant and benign lesions.
Eighty-four patients were treated in this 5-year span. The average residual daily
setup uncertainty was 0.48 (0.19) mm. We compare measurements of setup
uncertainty from the Extend system to measurements performed with a linac-based
approach previously used in our center. The Extend system has significantly
reduced setup uncertainty for fractionated intracranial treatments at our
institution. Positive results were observed in a small population of edentulous
patients. The Extend system compares favorably with other approaches to
delivering intracranial stereotactic radiotherapy and is a robust, simple-to-use,
and precise method for treating multisession intracranial lesions.
PMID- 28514898
TI - Assessment of Cryosurgical Device Performance Using a 3D Tissue-Engineered Cancer
Model.
AB - As the clinical use of cryoablation for the treatment of cancer has increased, so
too has the need for knowledge on the dynamic environment within the frozen mass
created by a cryoprobe. While a number of factors exist, an understanding of the
iceball size, critical isotherm distribution/penetration, and the resultant
lethal zone created by a cryoprobe are critical for clinical application. To this
end, cryoprobe performance is typically characterized based on the iceball size
and temperature penetration in phantom gel models. Although informative, these
models do not provide information as to the impact of heat input from surrounding
tissue nor give any information on the ablative zone created. As such, we
evaluated the use of a tissue-engineered tumor model (TEM) to assess cryoprobe
performance including iceball size, real-time thermal profile distribution, and
resultant ablative zone. Studies were conducted using an Endocare V-probe
cryoprobe, with a 10/5/10 double freeze-thaw protocol using prostate and renal
cancer TEMs. The data demonstrate the generation of a 33- to 38-cm3 frozen mass
with the V-Probe cryoprobe following the double freeze of which ~12.7 and 6.5 cm3
was at or below -20 degrees C and -40 degrees C, respectively. Analysis of
ablation zone using fluorescence microscopy 24 hours postthaw demonstrated that
the internal ~40% of the frozen mass was completely ablated, whereas in the
periphery of the iceball (outer 1 cm region), a gradient of partial to minimal
destruction was observed. These findings correlated well with clinical reports on
renal and prostate cancer cryoablation. Overall, this study demonstrates that
TEMs provide an effective model for a more complete characterization of
cryoablation device performance. The data demonstrate that while the overall
iceball size generated in the TEM was consistent with published reports from
phantom models, the integration of an external heat load, circulation, and
cellular components more closely reflect an in vivo setting and the impact of
penetration of the critical (-20 degrees C and -40 degrees C) isotherms into the
tissue. This is important as it is well appreciated in clinical practice that the
heat load of a tissue, cryoprobe proximity to vasculature, and so on, can impact
outcome. The TEM model provides a means of characterizing the impact on ablative
dose delivery allowing for a better understanding of probe performance and
potential impact on ablative outcome.
PMID- 28514900
TI - A QM/QTAIM detailed look at the Watson-Crick<->wobble tautomeric transformations
of the 2-aminopurine.pyrimidine mispairs.
AB - This work is devoted to the careful QM/QTAIM analysis of the evolution of the
basic physico-chemical parameters along the intrinsic reaction coordinate (IRC)
of the biologically important 2AP.T(WC)<->2AP.T*(w) and 2AP.C*(WC)<->2AP.C(w)
Watson-Crick(WC)<->wobble(w) tautomeric transformations obtained at each point of
the IRC using original authors' methodology. Established profiles reflect the
high similarity between the courses of these processes. Basing on the scrupulous
analysis of the profiles of their geometric and electron-topological parameters,
it was established that the dipole-active WC<->w tautomerizations of the Watson
Crick-like 2AP.T(WC)/2AP.C*(WC) mispairs, stabilized by the two classical N3H?N1,
N2H?O2 and one weak C6H?O4/N4 H-bonds, into the wobble 2AP.T*(w)/2AP.C(w) base
pairs, respectively, joined by the two classical N2H?N3 and O4/N4H?N1 H-bonds,
proceed via the concerted stepwise mechanism through the sequential intrapair
proton transfer and subsequent large-scale shifting of the bases relative each
other, through the planar, highly stable, zwitterionic transition states
stabilized by the participation of the four H-bonds - N1+H?O4-/N4-, N1+H?N3-,
N2+H?N3-, and N2+H?O2-. Moreover, it was found out that the 2AP.T(WC)<
>2AP.T*(w)/2AP.C*(WC)<->2AP.C(w) tautomerization reactions occur non
dissociatively and are accompanied by the consequent replacement of the 10 unique
patterns of the specific intermolecular interactions along the IRC. Obtained data
are of paramount importance in view of their possible application for the control
and management of the proton transfer, e.g. by external electric or laser fields.
PMID- 28514901
TI - Fixed-bed study for bone char adsorptive removal of refractory organics from
electrodialysis concentrate produced by petroleum refinery.
AB - Water reuse in industrial processes has been an increasing need encouraged in
recent years. However, as the streams are recycled, solutes accumulate, thus
requiring purification techniques. Membrane processes (reverse osmosis and
electrodialysis) have been implemented and in order to increase the reuse of
water at its highest level, crystallization has been evaluated to remove salts
from the concentrate produced and get a feasible disposal. Nevertheless,
contaminants affect the crystallization performance, thus making the removal of
residual organics important for both the efficiency of crystallization and the
increase of water reuse. In this context, aiming at establishing a sustainable
virtuous circle, bone char (0.5-1.4 mm particle size, mesoporous structure) was
used to remove refractory organics from an electrodialysis concentrate effluent
(C-EDR) from a Brazilian petroleum refinery, at a lab-scale, in a fixed-bed
adsorption column. Bone char selectively and partially removed the refractory
organics, a complex mixture of long-chain hydrocarbons, aromatic compounds,
carboxylic acids, amines and amides. The maximum adsorption capacity increased
with the increase in bed depth and reduction in flow rate. A maximum removal of
35.60 mg g-1 was achieved for the highest bed depth evaluated (12.9 cm). The
breakthrough curves indicated that bone char could adsorb part of the organic
compounds from the C-EDR. The scaling up was possible for the C/C0 ratios of
0.55, 0.60 and 0.65, providing a service time at about 16 days for 45% removal
efficiency for typical real operational conditions used in the refinery.
PMID- 28514902
TI - Performance of modified anaerobic inclining-baffled reactor treating recycled
paper mill effluent: effects of influent chemical oxygen demand concentration and
hydraulic retention time.
AB - The performance of modified anaerobic inclining-baffled reactor (MAI-BR) treating
recycled paper mill effluent (RPME) was investigated by varying the influent
chemical oxygen demand (CODin) concentration from 1000 to 4000 mg/L, and the
hydraulic retention time (HRT) from 3 to 1 day, corresponding to an organic
loading rate increase from 0.33 to 4 g COD/L day. Throughout 126 days of
operation, a maximum removal efficiency of up to 96% of chemical oxygen demand
(COD) and 99% of biological oxygen demand, methane (CH4) yield of 0.259 L CH4/g
COD, and a stable effluent pH of 6.5 were achieved. Furthermore, the
compartmental performance showed that most of the organic substrates were removed
in the initial two compartments, resulting in low pH and alkalinity levels and a
high concentration of volatile fatty acids. Overall, the results showed that the
MAI-BR successfully treated RPME, and the performance was affected by the
variation of HRT more than the CODin.
PMID- 28514903
TI - Utility of the central motor conduction time recorded from the abductor pollicis
brevis and the abductor digiti minimi muscles in patients with C6-7 myelopathy.
AB - OBJECTIVE: Central motor conduction time (CMCT) recorded from the abductor
pollicis brevis (CMCT-APB) and abductor digiti minimi (CMCT-ADM) muscles may
enable the evaluation of patients with C6-7 myelopathy. CMCT is more useful for
the evaluation of the function of spinal cord than magnetic resonance imaging
(MRI) findings. CMCT may be associated with age and height. However, there are
few reports regarding CMCT-APB in normal subjects. This study aimed to
investigate the relationships between age, height, and conduction parameters in
normal subjects to assess the effectiveness of using CMCT-APB and CMCT-ADM for
the evaluation of patients with C6-7 and C7-T1 myelopathy. DESIGN: Retrospective
study. METHODS: Fifteen patients with cervical compressive myelopathy at C6-7 (11
patients) or C7-T1 (4 patients) level were enrolled. The control group consisted
of 150 normal subjects (mean age 45.8+/-17.0 years; mean height 163.6+/-8.9 cm).
Motor evoked potentials induced by transcranial magnetic stimulation and F-waves
were used to determine CMCT. OUTCOME MEASURES: CMCT-APB, CMCT-ADM. RESULTS: The
normative values of CMCT-APB and CMCT-ADM were 5.3+/-0.7 ms and 5.2+/-0.8 ms,
respectively. CMCT-APB was significantly longer than CMCT-ADM for patients with
C6-7 myelopathy (P < 0.05). Neither of the CMCTs for those with C7-T1 myelopathy
were significantly different from those of controls, but CMCT-APB was more
prolonged than CMCT-ADM in patients with C6-C7 myelopathy. CONCLUSIONS: CMCTs
improve the accuracy of the diagnosis of myelopathy by pinpointing the lesion in
combination with MRI imaging. Selective CMCT-APB prolongation may be seen in
patients with C6-7 myelopathy but not C7-T1 myelopathy.
PMID- 28514905
TI - Evodiamine Prevents Glioma Growth, Induces Glioblastoma Cell Apoptosis and Cell
Cycle Arrest through JNK Activation.
AB - Evodiamine (EVO) is an active medicinal compound derived from the traditional
herbal medicine Evodia rutaecarpa. It has been reported that evodiamine has
several beneficial biological properties, including anticancer and anti
inflammatory activities. However, the in vitro and in vivo anticancer activities
of EVO against the growth of glioblastoma cells remain undefined. EVO induced
significant decreases in the viability of U87 and C6 glioma cells, but not of
primary astrocytes, according with the occurrence of apoptotic characteristics
including DNA ladders, caspase-3 and poly(ADP ribose) polymerase (PARP) protein
cleavage, and hypodiploid cells. The disruption of the mitochondrial membrane
potential (MMP) was detected, and it was found that the peptidyl caspase-9
inhibitor, Z-LEHD-FMK, significantly prevented glioma cells from EVO-induced
apoptosis. Increased c-Jun N-terminal kinase (JNK) protein phosphorylation by EVO
was observed, and the addition of JNK inhibitors, SP600125 and JNKI inhibited the
EVO-induced apoptosis was inhibited. Additionally, EVO treatment induced G2/M
arrest with increased polymerized tubulin protein expression in U87 and C6 cells.
Elevated expressions of the cyclin B1, p53, and phosphorylated (p)-p53 proteins
were detected in EVO-treated glioma cells, and these were inhibited by JNK
inhibitors. An in vivo study showed that EVO significantly reduced the growth of
gliomas elicited by the subcutaneous injection of U87 cells with increases in
cyclin B1, p53, and p-p53 protein expressions in tumors. An analysis of eight EVO
related chemicals showed that alkyl groups at position 14 in EVO are important
for its anti-glioma effects which involve both apoptosis and G2/M arrest.
Evidence is provided that supports EVO induction of apoptosis and G2/M arrest via
the activation of JNK-mediated gene expression and disruption of MMP in
glioblastoma cells. EVO was shown to penetrate the blood-brain barrier; EVO is
therefore predicted to be a promising compound for the chemotherapy of
glioblastomas and deserves further investigations.
PMID- 28514904
TI - Effects of Viola mandshurica on Atherosclerosis and Hepatic Steatosis in
ApoE[Formula: see text] via the AMPK Pathway.
AB - Atherosclerosis was previously thought to be a disease that primarily involves
lipid accumulation in the arterial wall. In this report, we investigated the
effect of Viola mandshurica W. Becker (V. mandshurica) water extract on
atherosclerosis in apolipoprotein E deficient (ApoE[Formula: see text]) mice. The
administration of V. mandshurica to high-fat diet-fed mice reduced body weight,
liver weight, and serum levels of lipids (total cholesterol, low-density
lipoprotein-cholesterol, triglycerides), glucose, alanine transaminase, and
aspartate transaminase. Histopathologic analyses of the aorta and liver revealed
that V. mandshurica attenuated atherosclerotic lesions and reduced lipid
accumulation, inflammatory responses and fatty acid synthesis. V. mandshurica
also increased phosphorylation of adenosine monophosphate-activated protein
kinase (AMPK), thereby reducing acetyl-CoA carboxylase (ACC) in liver tissue and
inhibiting sterol regulatory element-binding protein 1c (SREBP-1c). V.
mandshurica reduced protein expression levels of adhesion molecules
(intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E
selectin) as well as ACC, fatty acid synthase, and SREBP-1c. In addition,
quantitative analysis of V. mandshurica by high-performance liquid chromatography
revealed the presence of esculetin and scopoletin. Esculetin and scopoletin
reduced adhesion molecules in human aortic smooth muscle cells. Our results
indicate that the anti-atherosclerotic effects of V. mandshurica may be
associated with activation of the AMPK pathway. Therefore, AMPK-dependent
phosphorylation of SREBP-1c by V. mandshurica may be an effective therapeutic
strategy for combatting atherosclerosis and hepatic steatosis.
PMID- 28514906
TI - The Effects of Gymnema sylvestre in High-Fat Diet-Induced Metabolic Disorders.
AB - This study used an integrated approach to investigate the effects of Gymnema
sylvestre (GS) extract as a functional dietary supplement with a high-fat diet.
This approach examined insulin resistance, the dysfunction of adipose tissue, and
liver steatosis. Male C57BL/6J mice were fed a normal chow or high-fat diet (HFD)
for the acute and chronic study, in addition to GS in different doses (100, 250
and 500[Formula: see text]mg/kg body weight). Their body composition changes,
serum lipid and glucose parameters, adipose and liver tissue histology, and gene
expression were measured. It was found that GS significantly suppressed the
increase of body weight, serum levels of lipid, insulin and leptin, and adipose
tissue, and liver inflammation. GS also demonstrated hypoglycemic effects due to
the amylase inhibition activity. Our results support the existence of a
relationship between the HFD induced insulin resistance, adipose dysfunction and
liver steatosis. In conclusion, GS works as a functional dietary supplement with
preventative effects against metabolic disorder.
PMID- 28514907
TI - Nudging for Prevention in Occupational Health and Safety in South Africa Using
Fiscal Policies.
AB - Currently, in some countries occupational health and safety policy and practice
have a bias toward secondary prevention and workers' compensation rather than
primary prevention. Particularly, in emerging economies, research has not
adequately contributed to effective interventions and improvements in workers'
health. This article, using South Africa as a case study, describes a methodology
for identifying candidate fiscal policy interventions and describes the policy
interventions selected for occupational health and safety. It is argued that
fiscal policies are well placed to deal with complex intersectoral health
problems and to focus efforts on primary prevention. A major challenge is the
lack of empirical evidence to support the effectiveness of fiscal policies in
improving workers' health. A second challenge is the underprioritization of
occupational health and safety partly due to the relatively small burden of
disease attributed to occupational exposures. Both challenges can and should be
overcome by (i) conducting policy-relevant research to fill the empirical gaps
and (ii) reconceptualizing, both for policy and research purposes, the role of
work as a determinant of population health. Fiscal policies to prevent exposure
to hazards at work have face validity and are thus appealing, not as a
replacement for other efforts to improve health, but as part of a comprehensive
effort toward prevention.
PMID- 28514908
TI - Using action learning sets to support change in end-of-life care.
AB - Purpose The purpose of this paper is to describe the delivery of facilitated
action learning sets as an integral component of a multidisciplinary end-of-life
care course. Design/methodology/approach The educational intervention described
in this paper is delivered by specialist palliative care practitioners to those
working with dying patients and their families in non-specialist settings. The
programme consists of two components: the first taught/experience-based component
takes place in a hospice. The second integral component involves action learning
sets which are facilitated by specialist palliative care staff over a six-month
period. This paper reports the challenges, learning and benefits of using action
learning sets to improve end-of-life care. Findings Action learning sets provide
support which enables staff to implement changes to end-of-life care.
Participants in the successful action learning sets were motivated to change
practice and identified themselves as change agents. Management support was vital
to allow participants the authority to implement changes to practice. Practical
implications Facilitators need to gain participant and management commitment to
the action learning process before the programme begins if they are to be
successful in achieving changes to end-of-life care. Originality/value Hospices
and other health care organisations work in partnership to deliver this
programme, and this paper demonstrates how action learning sets can increase
mutual understanding and communication between specialist and non-specialist end
of-life care settings.
PMID- 28514909
TI - What can action learning offer a beleaguered system? A narrative representing the
relationship.
AB - Purpose This is an attempt to write an account of action learning that is as
close to the ground on which it was practised as the author can make it. In that
sense, the reader can read what follows below as a kind of autoethnography, a
"representation as relationship" as Gergen and Gergen (2002, p. 11) call it. This
is because in the opportunity of telling a story about his practice as an action
learning facilitator, the author hopes to evoke that which is more akin to the
contactful environment of quality action learning than any amount of abstract
theorising. Design/methodology/approach This is an example of "narrative
inquiry", best judged, according to Sparkes (2002), in terms of the ability of
such accounts to "contribute to sociological understanding in ways that, amongst
others are self-knowing, self-respecting, self-sacrificing and self-luminous".
Findings As the author re-tells this partial account, he has a sense of the
massive wider structures around him, but all he can see in his dim lamp is the
fleeting glimpse of the local strata. The author traces his hand along the seams,
not intending to dig them out, but simply to witness them, or even, in a spirit
of yearning, to give them a witnessing of themselves. Originality/value To the
author, this is about portraying what action learning feels like, rather than
thinks like, for his own and for the benefit of other practitioners.
PMID- 28514910
TI - Value-based healthcare measurement as a context for organizational learning.
AB - Purpose The purpose of this paper is to shed light on the potential of
organizational learning for developing effectiveness of care. Value-based
healthcare measurement recognizes patient value as a driver for improving health
outcomes at the societal and individual levels. By using the action learning
method, this paper examines the phases of organizational learning in a private
healthcare organization that has developed a novel Big Data screening tool for
the treatment of patients with type 2 diabetes mellitus (DM2).
Design/methodology/approach Relying on triple-loop learning as a conceptual
framework and by applying the action learning method to case study design, this
paper illustrates the phases of organizational learning and efforts to utilize
value-based measurement in healthcare. Findings The case organization was able to
identify patients at risk and to improve their care balance. Although the results
for the measurement of patient outcomes led to questioning of previous care
processes and practices in the organization, increasing value for all
stakeholders by incorporating social needs to business opportunities remains
under process. Originality/value With the focus on organizational learning and
organizational value creation processes, this paper demonstrates incorporation of
measuring patient outcomes in re-structuring care processes, enhancing
organizational performance and improving effectiveness as well as quality of
care.
PMID- 28514911
TI - Action learning across the decades.
AB - Purpose The purpose of this paper is to explore how action learning concepts were
used in two healthcare projects undertaken many decades apart. The specific
purpose in both cases was to examine how action learning can contribute to shared
learning across key stakeholders in a complex socio-technical system. In each
case study, action learning supported joint design programmes and the sharing of
perspectives about the complex system under investigation.
Design/methodology/approach Two action learning projects are described: first,
the Hospital Internal Communications (HIC) project led by Reg Revans in the
1960s. Senior staff in ten London hospitals formed action learning teams to
address communication issues. Second, in the Better Outcomes for People with
Learning Disabilities: Transforming Care (BOLDTC) project, videoconferencing
equipment enabled people with learning disabilities to increase their
opportunities to communicate. A mutual learning process was established to enable
stakeholders to explore the potential of the technical system to improve
individual care. Findings The HIC project demonstrated the importance of evidence
being shared between team members and that action had to engage the larger
healthcare system outside the hospital. The BOLDTC project confirmed the
continuing relevance of action learning to healthcare today. Mutual learning was
achieved between health and social care specialists and technologists.
Originality/value This work draws together the socio-technical systems tradition
(considering both social and technical issues in organisations) and action
learning to demonstrate that complex systems development needs to be undertaken
as a learning process in which action provides the fuel for learning and design.
PMID- 28514912
TI - Team sponsors in community-based health leadership programs.
AB - Purpose The purpose of this article is to share the lessons learned about the
role of team sponsors in action-learning teams as part of community-based health
leadership development programs. Design/methodology/approach This case study uses
program survey results from fellow participants, action learning coaches and team
sponsors to understand the value of sponsors to the teams, the roles they most
often filled and the challenges they faced as team sponsors. Findings The extent
to which the sponsors were perceived as having contributed to the work of the
action learning teams varied greatly from team to team. Most sponsors agreed that
they were well informed about their role. The roles sponsors most frequently
played were to provide the teams with input and support, serve as a liaison to
the community and serve as a sounding board, motivator and cheerleader. The most
common challenges or barriers team sponsors faced in this role were keeping
engaged in the process, adjusting to the role and feeling disconnected from the
program. Practical implications This work provides insights for program
developers and community foundations who are interested in building the capacity
for health leadership by linking community sponsors with emerging leaders engaged
in an action learning experience. Originality/value This work begins to fill a
gap in the literature. The role of team sponsors has been studied for single
organization work teams but there is a void of understanding about the role of
sponsors with multi-organizational teams working to improve health while also
learning about leadership.
PMID- 28514913
TI - Action learning: ripples within and beyond the set.
AB - Purpose This paper aims to explore the impact of action learning (AL) on an
individual and an organisation, particularly the process by which each affected
the other. The organisation is a UK National Health Service (NHS) Trust that
includes two hospitals. Design/methodology/approach This is a single person case
study involving a clinician, but the voice of an author can also be heard. It
involves the experience of the individual as they experience AL as part of a
leadership development programme leading to a postgraduate certificate. The
authors explain their caution of the case study approach and in doing so offer
their thoughts in how this paper could be read and impact on practice. Findings
The authors show a process whereby an AL set participant moves from being
confident about their project to one of uncertainty as the impact of the project
ripples throughout the organisation. Through this process of unsettlement, the
individual's unnoticed assumptions are explored in ways that enable practical
action to be taken. In doing so, the individual's leadership and identity
developed. Research limitations/implications This is a single person case study
in one organisation, thus affecting wider generalisation. Originality/value This
single case study contributes to the debate on critical AL and the use of AL in
the NHS.
PMID- 28514914
TI - Using action learning to reduce health inequity in Danish municipalities.
AB - Purpose The aim of this study is to clarify how action learning can be used as a
vehicle for promoting equal access to municipal health services for socially
disadvantaged groups in a Danish context. It is the purpose of this paper to
describe the methods for reducing health inequity developed in the study and to
discuss how action learning methodologically contributed to achieving these
results. Design/methodology/approach In the study, the front-line staff from 19
health and social service units in six different municipalities, in Denmark, each
formed an action learning group to develop methods for reducing health inequity
in a municipal health setting. Each group was guided by an external facilitator,
according to an Action Learning Action Research phase model (ALAR-model), which
structured the cyclical development of methods into four phases: diagnosing,
planning action, taking action and evaluating action. Findings Two types of
results of the study are reported in the paper. First, the authors present an
overview of the results the 19 participating municipal units have achieved in
their action learning processes, as well as two case examples of how two units
have worked with action learning and the concrete methods and tools they have
developed in this process. Second, they report the challenges and dilemmas the 19
units faced when working with action learning in the study. Originality/value
With its use of action learning techniques and the ALAR-model, this study
contributes to the development of practice-based methods to reduce unequal access
to municipal health services for socially disadvantaged groups. Through the
study, the front-line staff in the health and social service units has been
involved in the problem-solving process, to a much greater extent than it has
previously been adopted in a Danish municipal health setting.
PMID- 28514915
TI - Foreword.
PMID- 28514916
TI - Guest editorial.
PMID- 28514917
TI - Advancing health care quality and safety through action learning.
AB - Purpose The purpose of this study is to demonstrate how action learning can be
practically applied to quality and safety challenges at a large academic medical
health system and become fundamentally integrated with an institution's broader
approach to quality and safety. Design/methodology/approach The authors describe
how the fundamental principles of action learning have been applied to advancing
quality and safety in health care at a large academic medical institution. The
authors provide an academic contextualization of action learning in health care
and then transition to how this concept can be practically applied to quality and
safety by providing detailing examples at the unit, cross-functional and
executive levels. Findings The authors describe three unique approaches to
applying action learning in the comprehensive unit-based safety program, clinical
communities and the quality management infrastructure. These examples,
individually, provide discrete ways to integrate action learning in the
advancement of quality and safety. However, more importantly when combined, they
represent how action learning can form the basis of a learning health system
around quality and safety. Originality/value This study represents the broadest
description of action learning applied to the quality and safety literature in
health care and provides detailed examples of its use in a real-world context.
PMID- 28514918
TI - Does vitamin D deficiency affect placental inflammation or infections among very
low birth weight infants?
AB - OBJECTIVE: Examine the association between placental inflammation and neonatal
infections, and 25OH vitamin D (25OH D) levels at birth among very low birth
weight infants (VLBWI). STUDY DESIGN: Serum 25OH D levels were measured in 89
VLBWI (<=1250 g) and 47 mothers on day one, and in 78 infants on day 21.
Placentas were examined for maternal and fetal inflammation. Infants were divided
into deficient (<=10 ng/ml) and adequate (>10 ng/ml) groups based on 25OH D
levels on day 1. RESULTS: Mean +/- SD maternal levels of 25OH D (21 +/- 9 ng/ml)
correlated with infants' levels (15 +/- 8 ng/ml), (p < .001). 25OH D levels were
lower in deficient (32/89) than in adequate group (8 +/- 2 versus 20 +/- 7 ng/ml,
p = .011). Infants' 25OH D levels rose significantly by day 21 (p < .001).
Univariate analyses showed no differences between infant groups in maternal or
fetal inflammation, or neonatal infections (p > .05). Logistic regression
analyses revealed no association between deficient 25OH D levels and the odds of
maternal or fetal inflammation or other infections. Levels of 25OH D did not
correlate with severity of placental inflammation. CONCLUSIONS: Deficient levels
of 25OH D at birth are not associated with the occurrence of placental
inflammation or neonatal infections among VLBWI.
PMID- 28514919
TI - Periconceptional CMV infection prevention in Portugal: population subgroup study
in a tertiary perinatal care center.
AB - Currently in Portugal, universal screening of pregnant women for Cytomegalovirus
(CMV) infection is not performed. However, it is recommended to screen all women
attending preconception care. We aimed to assess women's attendance to
preconception care and if their serologic status regarding CMV was known and/or
investigated in that consultation. In this cross-sectional study, we interviewed
240 women admitted to the obstetrical ward of a hospital in the Metropolitan Area
of Porto (Portugal) about their adherence to preconception care and collected
data regarding their CMV serologic status and its investigation. We found that
71.3% of the women who attended preconception care were not screened for CMV
infection. Among primigravida, the screening rate was only of 30.4% (upper limit
of CI 95%: 44.8%). There were no statistically significant differences between
the private and public sectors of healthcare. We observed attendance to
preconception care is high (73.1%). For the population subgroup of the
metropolitan area of Porto, attendance to preconception care is at least 66%,
with a 95% confidence level. Portuguese guidelines stating a woman's serologic
status regarding CMV should be investigated in preconception care are not
properly implemented. This suggests guidelines should assure the screening of
previously non-screened women during pregnancy.
PMID- 28514920
TI - Predicting Factors of Zone 4 Attack in Volleyball.
AB - This study examined 142 volleyball games of the Men's Super League 2014/2015
seasons in Brazil from which we analyzed 24-26 games of each participating team,
identifying 5,267 Zone 4 attacks for further analysis. Within these Zone 4
attacks, we analyzed the association between the effect of the attack carried out
and the separate effects of serve reception, tempo and type of attack. We found
that the reception, tempo of attack, second tempo of attack, and power of
diagonal attack were predictors of the attack effect in Zone 4. Moreover, placed
attacks showed a tendency to not yield a score. In conclusion, winning points in
high-level men's volleyball requires excellent receptions, a fast attack tempo
and powerfully executed of attacks.
PMID- 28514921
TI - A Study of Relationships among Technical, Tactical, Physical Parameters and Final
Outcomes in Elite Soccer Matches as Analyzed by a Semiautomatic Video Tracking
System.
AB - The performance of a soccer team depends on many factors such as decision-making,
cognitive and physical skills, and dynamic ever-changing space-time interactions
between teammate and opponents in relation to the ball. Seventy ( n = 70) matches
of the Italian SERIE A season 2013-2014 were investigated to analyze the mean
performance of 360 players in terms of physical (physical efficiency index; PEI)
and technical-tactical (technical efficiency index; TEI) standpoints. Using a
semiautomatic video analysis system that has incorporated new parameters able to
measure technical-tactical and physical efficiency (Patent IB2010/002593, 2011
ISA), the correlation between these new variables and how much it relates to the
likelihood of winning were verified. Correlations between TEI and PEI were
significant ( n = 140, r = .60, p < .001), and TEI showed a higher likelihood of
winning than PEI factors ( p < .0001 vs. .0001, CI 95% [1.64, 3.00] vs. [1.28,
2.07]). Higher TEI and TEI + PEI differences between the teams were associated
with a greater likelihood of winning, but PEI differences were not. Key
performance indicators and this performance assessment method might be useful to
better understand what determines winning and to assist the overall training
process and match management.
PMID- 28514922
TI - Effects of Youth Participation in Extra-Curricular Sport Programs on Perceived
Self-Efficacy: A Multilevel Analysis.
AB - The present study examined extracurricular sport participation variables and
developmental context in relationship to perceived self-efficacy among
underserved adolescents. Participants ( n = 821, 13.6 +/- 1.5 years) completed
the Youth Experience in Sport questionnaire and General Self-Efficacy Scale. We
used the Human Development Index (HDI) to characterize developmental contexts.
Multilevel regression models were used to explore the relative contributions of
age, sex, years of participation in extracurricular sport, HDI, and perceived
positive experience in sport. Our results highlight that positive experience
alone and in interaction with length of participation in the program fostered
perceived self-efficacy. Participants from higher HDI contexts remained longer in
the program. An implication of our research is that variables linked to positive
sport experiences and perceived self-efficacy can be used as markers to evaluate
the outcomes and impact of sport participation programs aimed at promoting
positive youth development.
PMID- 28514923
TI - Object-Spatial Imagery and Verbal Cognitive Styles in High School Students.
AB - The present study investigated object-spatial imagery and verbal cognitive styles
in high school students. We analyzed the relationships between cognitive styles,
object imagery ability, spatial visualization ability, verbal-logical reasoning
ability, and preferred modes of processing math information. Data were collected
from 348 students at six high schools in two school districts. Spatial imagery
style was not correlated with object imagery style and was negatively correlated
with verbal style. Object imagery style did not correlate significantly with any
cognitive ability measure, whereas spatial imagery style significantly correlated
with object imagery ability, spatial visualization ability, and verbal-logical
reasoning ability. Lastly, spatial imagery style and verbal-logical reasoning
ability significantly predicted students' preference for efficient visual
methods. The results support the cognitive style model, in which visualizers are
characterized as two distinct groups who process visual-spatial information and
graphic tasks in different ways.
PMID- 28514924
TI - Rapid and annealing-free self-assembly of DNA building blocks for 3D hydrogel
chaperoned by cationic comb-type copolymers.
AB - The construction and self-assembly of DNA building blocks are the foundation of
bottom-up development of three-dimensional DNA nanostructures or hydrogels.
However, most self-assembly from DNA components is impeded by the mishybridized
intermediates or the thermodynamic instability. To enable rapid production of
complicated DNA objects with high yields no need for annealing process, herein
different DNA building blocks (Y-shaped, L- and L'-shaped units) were assembled
in presence of a cationic comb-type copolymer, poly (L-lysine)-graft-dextran (PLL
g-Dex), under physiological conditions. The results demonstrated that PLL-g-Dex
not only significantly promoted the self-assembly of DNA blocks with high
efficiency, but also stabilized the assembled multi-level structures especially
for promoting the complicated 3D DNA hydrogel formation. This study develops a
novel strategy for rapid and high-yield production of DNA hydrogel even derived
from instable building blocks at relatively low DNA concentrations, which would
endow DNA nanotechnology for more practical applications.
PMID- 28514925
TI - Factors affecting cell-free DNA fetal fraction and the consequences for test
accuracy.
AB - INTRODUCTION: Biological factors are known to influence the fetal fraction (FF)
of cell-free DNA and may also influence the accuracy of non-invasive prenatal
testing. MATERIAL AND METHODS: NIPT from 5267 mixed risk women across three
specialist clinics in Australia were analyzed. Multivariable regression analysis
was used to determine whether maternal characteristics, ultrasound, and placental
biomarkers affect FF and test accuracy. RESULTS: FF ranged from 4% to 37% (mean
11.6%). Body mass index (BMI), gestation, and placental biomarkers were found to
be significant factors associated with FF. For each unit increase in BMI, the
logarithmically transformed FF, (lnFF), mean value decreased by 0.027. Each week
increases in gestation, lnFF increased by 0.023. Each unit increase in free BhCG,
PAPPA, and PlGF, the lnFF increased by 0.065, 0.050, and 0.17, respectively.
There was no significant association between FF with either maternal age or
nuchal translucency. The false-positive cases and one false-negative case did not
have lower FF than the true-positive cases. DISCUSSION: The fetal fraction in
maternal plasma cfDNA increased with gestational age, serum pregnancy-associated
plasma protein A (PAPP-A), beta-hCG, and PlGF and decreased with increasing
maternal BMI. There was no significant correlation between low FF and test
accuracy, when FF was above 4%.
PMID- 28514927
TI - La vida normal: living with HIV in Santo Domingo, Dominican Republic.
AB - In this study, we explore how individuals living with HIV in the Dominican
Republic strive to live a 'normal' life and the consequences of this pursuit of
normalcy. We conducted qualitative in-depth interviews with men (n = 20) and
women (n = 20) living with HIV and receiving care at two urban clinics in Santo
Domingo. We analysed the data using a combination of narrative analysis and
thematic coding. We aimed to identify how fears and/or lived experiences with
social rejection and HIV-related stigma and discrimination shaped participants'
abilities to maintain social relationships, be economically productive and manage
HIV within the context of sexual relationships. Participants used the discourse
of una vida normal (a normal life) to frame their response to HIV. This pursuit
of normality was driven by the social and economic pressures of living with a
chronic condition in a context of HIV-related stigma; trying to keep things
'normal' further added to these pressures. We argue that the normal life
discourse fails to recognise the dynamic and complex nature of negotiating this
condition and may also create additional burdens for individuals living with HIV
that could impact their wellbeing and preventive behaviours.
PMID- 28514926
TI - Trunk muscle activity patterns and motion patterns of patients with motor
complete spinal cord injury at T8 and T10 walking with different un-powered
exoskeletons.
AB - OBJECTIVE: The aim of this study was to explore how neurological injured levels
of spinal cord affect the performance of patients walking with different un
powered exoskeletons. STUDY DESIGN: Case series observational study. SETTING:
Gait and Motion Analysis Laboratory at the National Research Center
Rehabilitation Technical Aids. METHODS: Electromyography and motion data from two
subjects with complete spinal cord injury at T10 and T8 walking with un-powered
exoskeletons were collected simultaneously. OUTCOME MEASURES: Surface
electromyography of trunk muscles and motion data including joint angle and
center of mass (COM). RESULTS: Compared to T10 subject, T8 subject activated
trunk muscles in higher levels walking with all tested un-powered exoskeletons
and had greater pelvic obliquity walking with reciprocating gait orthosis (RGO)
and energy-stored exoskeleton (ES-EXO). ES-EXO can redistribute muscle forces,
recruit trunk muscles evenly, increase walking speed and improve COM trajectory
in frontal plane. CONCLUSION: This study revealed differences in kinematics and
muscle activities in walking with three un-powered exoskeletons between two
patients with different neurological injured levels. ES-EXO had advantages over
conventional un-powered exoskeletons on recruiting muscles evenly and improving
walking speed, step length and COM trajectory.
PMID- 28514928
TI - Challenges in evaluation of screening for gastric cancer among men based on
nonrandomized design.
AB - BACKGROUND: Objective was to quantify biases in screening for gastric cancer when
comparing attenders to nonattenders using serum pepsinogen I (SPGI) level as
primary test. METHODS: In mid 1990s, all men aged 51-65 years from two Finnish
cities were invited to SPGI screening. Mortality and premature mortality in
attenders were compared to nonattenders. Efficacy of screening was studied by 15
years' follow-up of standardized mortality ratio (SMR) and potential years of
life lost (PYLL) due to gastric cancer. Bias due to selective attendance was
quantified using corrective coefficients based on total cancer incidence and
mortality, and gastric cancer-specific incidence and mortality for total
population and nonattenders. RESULTS: In 1994-1996, men aged 51-65 years (16,872)
were invited to SPGI assay and 12,175 men (72%) attended. SPGI was 25 microg/l or
less in 610 (5%) men, indicating severe atrophic gastritis (AG). Post-screening
gastroscopy was performed to 435 men with low SPGI. Of these, 168 men were
referred for treatment due to abnormal focal lesions. Attributable proportions in
reductions of SMR and PYLL from gastric cancer due to screening were 59% and 67%.
After correcting for selective participation, attributable proportions were
reduced to 23% and 39%. CONCLUSIONS: Biomarker screening by low SPGI among middle
aged men followed by upper gastrointestinal endoscopy decreased long-term and
premature mortality due to gastric cancer. However, in spite of methodological
corrections done, the results do not justify any firm conclusions or recommend
general screening programs. Randomized trials are warranted for this purpose.
PMID- 28514929
TI - Five-year outcomes from a prospective trial of image-guided accelerated
hypofractionated proton therapy for prostate cancer.
AB - PURPOSE: To report 5-year outcomes of a prospective trial of image-guided
accelerated hypofractionated proton therapy (AHPT) for prostate cancer. PATIENTS
AND METHODS: 215 prostate cancer patients accrued to a prospective institutional
review board-approved trial of 70Gy(RBE) in 28 fractions for low-risk disease (n
= 120) and 72.5Gy(RBE) in 29 fractions for intermediate-risk disease (n = 95).
This trial excluded patients with prostate volumes of >=60 cm3 or International
Prostate Symptom Scores (IPSS) of >=15, patients on anticoagulants or alpha
blockers, and patients in whom dose-constraint goals for organs at risk (OAR)
could not be met. Toxicities were graded prospectively according to Common
Terminology Criteria for Adverse Events (CTCAE), version 3.0. This trial can be
found on ClinicalTrials.gov (NCT00693238). RESULTS: Median follow-up was 5.2
years. Five-year rates of freedom from biochemical and clinical disease
progression were 95.9%, 98.3%, and 92.7% in the overall group and the low- and
intermediate-risk subsets, respectively. Actuarial 5-year rates of late radiation
related CTCAE v3.0 grade 3 or higher gastrointestinal and urologic toxicities
were 0.5% and 1.7%, respectively. Median IPSS before treatment and at 4+ years
after treatment were 6 and 5 for low-risk patients and 4 and 6 for intermediate
risk patients. CONCLUSIONS: Image-guided AHPT 5-year outcomes show high efficacy
and minimal physician-assessed toxicity in selected patients. These results are
comparable to the 5-year results of our prospective trials of standard
fractionated proton therapy for patients with low-risk and intermediate-risk
prostate cancer. Longer follow-up and a larger cohort are necessary to confirm
these findings.
PMID- 28514930
TI - Hypofractionated stereotactic body radiotherapy for localized prostate cancer -
first Nordic clinical experience.
AB - BACKGROUND: The use of hypofractionated stereotactic body radiotherapy (SBRT) as
primary treatment modality in clinically localized prostate cancer (PCa) is
emerging, because the low alpha/beta-ratio favors the use of high dose per
fraction in PCa. There is a need for more data about SBRT, especially in high
risk PCa patients. The purpose of this retrospective study was to evaluate the
safety and the short-term efficacy of robotic SBRT in a clinical patient cohort
with localized PCa including also high-risk patients (D'Amico risk
stratification). MATERIALS AND METHODS: A total of 240 consecutive patients with
clinically localized PCa were treated primarily with SBRT to total doses of 35 Gy
or 36.25 Gy in 5 fractions using a robotic SBRT device (CyberKnife(r)). All risk
groups (D'Amico risk stratification) were represented as follows: 48 (22%), 59
(27%) and 111 (51%) of the patients representing low-, intermediate- and high
risk group, respectively. Data on acute and intermediate-term toxicities and
early PSA responses were analyzed. RESULTS: Neither acute grade 3 or higher GU
nor rectal toxicity was observed. Regardless of the fact that 29 (13.3%) patients
experienced intermediate-term toxicity requiring diagnostic interventions, the
rates of intermediate-term grade 3 GU, rectal and infectious toxicity were low,
1.8%, 0.9% and 1.4%, respectively. A biochemical relapse was observed in ten
(4.6%) patients. With the median follow-up time of 23 months the biochemical
relapse-free survival (bRFS) rate was 100%, 96.6% and 92.8% in low-, intermediate
and high-risk group, respectively. CONCLUSIONS: The toxicity of robotic SBRT in
a large clinical cohort of PCa patients was tolerable and the early PSA response
was good in all risk groups. The hypofractionated SBRT offers a possibility to
high dose per fraction and to provide the whole radiotherapy treatment within two
to three weeks.
PMID- 28514931
TI - Lung cancer in never-smokers - what are the differences?
AB - INTRODUCTION: Characteristics of never-smokers with lung cancer are still not
fully clarified. The aim of this study was to compare never-smokers and ever
smokers with non-small cell lung cancer (NSCLC) regarding patient and tumor
characteristics. METHODS: All consecutive newly NSCLC patients with known smoking
status diagnosed between 2011 and 2015 were included in this retrospective cohort
study. Clinical, histological, and molecular characteristics were compared
between ever-smokers and never-smokers. RESULTS: Of the 558 included patients,
125 (22.4%) were never-smokers. These patients were more likely to be female (74%
vs. 7%, p < .001), older (67 vs. 66 years-old, p = .019), and have adenocarcinoma
(93% vs. 65%, p < .001). Never-smokers took longer to seek medical care after the
symptoms onset (3 vs. 2 months, p < .001), regardless of the symptoms,
histological type, or gender (OR: 1.2 [1.4-2.0]). The metastatic pattern was
different in never-smokers: pleural metastases were more frequent (OR: 2.1 [1.1
4.0]), regardless of the histological type and gender. Never-smokers had a higher
prevalence of ALK translocations (26% vs. 4%, p < .001) and EGFR mutations (36%
vs. 8%, p < .001). The type of EGFR mutation was also significantly different
between groups. CONCLUSIONS: Never-smokers with NSCLC present distinct
demographic and clinical characteristics. The characteristics of tumor also
differ between never-smokers and ever-smokers, which may suggest different
carcinogenic pathways.
PMID- 28514932
TI - Case report of severe maternal hyponatremia complicating preeclampsia.
AB - The incidence of preeclampsia associated maternal and neonatal hyponatremia is
reportedly rare and can be life threatening in severe cases. The timely diagnosis
and careful management requires a multidisciplinary approach between obstetric,
neonatal, endocrinology, and intensive care teams. We report firstly, on a case
of severe hyponatremia associated with preeclampsia, secondary to inappropriate
Anti-Diuretic Hormone secretion, followed by a review of cases over a one year
period at our institution.
PMID- 28514933
TI - Obituary notice: Dr John Moll.
PMID- 28514934
TI - A hypothesis: King Henry VIII's (1491-1547) personality change: A case of lead
poisoning?
AB - Henry VIII (1491-1547) became King of England in 1509. He started out as a good
monarch, sensible, reasonable and pleasant, but later his behaviour changed
drastically. He became irascible, intolerant, violent and tyrannical. In January
1536, Henry had a serious jousting accident and was unconscious for 2 h. It is
generally believed that this accident played a major role in his personality
change. Letters of that time, however, indicate that the change began insidiously
in 1534 and became most drastic in 1535, a year before the accident. Henry had
suffered from leg ulcers before and after the accident and had been constantly
treated for them for many years. Sloane MS1047, now in the British Library in
London, contains the prescriptions for the medications used to treat these
ulcers. Many of the medications contain a high proportion of lead in various
forms. Lead can be absorbed through skin, especially damaged skin. Absorbed lead
can affect the brain, causing psychiatric problems, especially those associated
with violence. The author presents a hypothesis that absorbed lead from his
medications might have been a major factor in King Henry's personality change.
PMID- 28514935
TI - Mesenchymal Stem Cell-Based Cartilage Regeneration Approach and Cell Senescence:
Can We Manipulate Cell Aging and Function?
AB - Aging is the most prominent risk factor triggering several degenerative diseases,
such as osteoarthritis (OA). Due to its poor self-healing capacity, once injured
cartilage needs to be reestablished. This process might be approached through
resorting to cell-based therapies and/or tissue engineering. Human mesenchymal
stem cells (MSCs) represent a promising approach due to their chondrogenic
differentiation potential. Presently, in vitro chondrogenic differentiation of
MSCs is limited by two main reasons as follows: aging of MSCs, which determines
the loss of cell proliferative and differentiation capacity and MSC-derived
chondrocyte hypertrophic differentiation, which limits the use of these cells in
cartilage tissue regeneration approach. The effect of aging on MSCs is
fundamental for stem cell-based therapy development, especially in older
subjects. In the present review we focus on homeostasis alterations occurring in
MSC-derived chondrocytes during in vitro aging. Moreover, we deal with potential
cell aging regulation approaches, such as cell stimulation through telomerase
activators, mechanical strain, and epigenetic regulation. Future investigations
in this field might provide new insights into innovative strategies for cartilage
regeneration and potentially inspire novel therapeutic approaches for OA
treatment.
PMID- 28514936
TI - Evaluation of an indirect oscillometric blood pressure monitor in anaesthetised
dogs at three different anatomical locations.
AB - AIMS: To evaluate the agreement between invasive and non-invasive measurements of
blood pressure (BP) using an oscillometer (PetTrust) at three different
anatomical locations in anaesthetised dogs under different haemodynamic
conditions. METHODS: Eight adult Greyhounds weighing 23.5-36.5 kg were
anaesthetised with isoflurane and positioned in dorsal recumbency. Systolic
arterial pressure (SAP), diastolic arterial pressure (DAP) and mean arterial
pressure (MAP) were measured invasively via a dorsal pedal artery and non
invasively using the oscillometer with cuffs placed above the carpus, above the
tarsus and around the tail base. Phenylephrine was administered to induce
vasoconstriction, dobutamine was used to increase cardiac output and increased
end-tidal concentrations of isoflurane were used to induce vasodilation.
Correlation between measurements was analysed by linear regression and agreement
was analysed using Bland-Altman plots. RESULTS: Seventy two representative
measurements were obtained. Mean differences (bias) between invasive and non
invasive measurements were <5 mmHg except for DAP measured on the tail, and SD
(precision) were <15 mm Hg except for SAP measured at the pelvic limb.
Correlation coefficients were >0.9 except for SAP on the pelvic limb and DAP on
the tail. More than 50 and 80% of values measured using oscillometry lay within
10 and 20 mmHg, respectively, of values measured invasively except for SAP on the
tail. SAP tended to be overestimated when measured non-invasively at low BP, and
be underestimated at high BP. DAP was underestimated during low BP and
overestimated during high BP. Hypotension (MAP <60 mmHg) was detected by the
oscillometer with a sensitivity >=83% and specificity >=98% at all locations.
CONCLUSIONS: This oscillometric device met the 2007 American College of
Veterinary Internal Medicine guidelines for measurement of BP on the thoracic
limb. There was good agreement between the oscillometer and invasive measurement
of MAP at all locations. CLINICAL RELEVANCE: MAP is the driving pressure for
tissue perfusion, thus MAP measurement is clinically essential. This
oscillometric device yields reliable MAP measurements at three anatomical
locations over a wide range of BP and can identify hypotension with high
sensitivity and specificity.
PMID- 28514937
TI - Removal of dibutyl phthalate from aqueous environments using a nanophotocatalytic
Fe, Ag-ZnO/VIS-LED system: modeling and optimization.
AB - An (Fe, Ag) co-doped ZnO nanostructure was synthesized by a simple chemical co
precipitation method and used for the degradation of dibutyl phthalate (DBP) in
aqueous solution under visible light-emitting diode (LED) irradiation. (Fe, Ag)
co-doped ZnO nanorods were characterized by powder X-ray diffraction, Fourier
transform infrared spectroscopy, UV-VIS diffuse reflectance spectroscopy,
elemental mapping, Field emission scanning electron microscopy, transmission
electron microscope and Brunauer-Emmett-Teller surface area analysis. A Central
Composite Design was used to optimize the reaction parameters for the removal of
DBP by the (Fe, Ag) co-doped ZnO nanorods. The four main reaction parameters
optimized in this study were the following: pH, time of radiation, concentration
of the nanorods and initial DBP concentration. The interaction between the four
parameters was studied and modeled using the Design Expert 10 software. A maximum
reduction of 95% of DBP was achieved at a pH of 3, a photocatalyst concentration
of 150 mg L-1 and a DBP initial DBP concentration of 15 mg L-1. The results
showed that the (Fe, Ag) co-doped ZnO nanorods under low power LED irradiation
can be used as an effective photocatalyst for the removal of DBP from aqueous
solutions.
PMID- 28514938
TI - Characterization and Standardization of Cultured Cardiac Fibroblasts for Ex Vivo
Models of Heart Fibrosis and Heart Ischemia.
AB - A full understanding of cardiac fibroblast (cFB) biology is essential to study
the adverse cardiac remodeling and recovery of myocardium infarction. However,
compared to cardiac myocytes, cFBs are less well characterized. Important
questions, including the variability introduced by cell age (neonatal vs. adult),
culture conditions (passage, plate coating, and culture medium), and responses to
stimuli (e.g., hypoxia and drug treatments), have not been well addressed and
standardization of techniques is lacking. This variability invites inconsistency
and the confounding of study conclusions. Thus, we here focus on characterizing
cell responses and standardizing procedures for cFB isolation and culture
conditions to provide reliable platforms to address important questions about cFB
proliferation, activation, collagen matrix formation, and responses to relevant
stimuli. Thirty litters of 1-3-day pups and 30 female (240-330 g) Sprague-Dawley
rats were used to isolate neonatal and adult cFBs. We detail and validate
procedures to isolate cFBs for the use of culture or direct analysis. We
characterize the differences between neonatal and adult cFBs, define the changes
of cFBs during serial passage, and identify the response of cFBs to different
culture conditions. We have also established models for the functional screening
of profibrotic and antifibrotic drugs based on cFB proliferation, myofibroblast
activation, and pericellular collagen matrix formation, and models of
hypoxia/reoxygenation with appropriate time course and media conditions to
achieve consistent cell injury. Our standardized procedures will ensure
consistency in assessing cFB function. This original contribution provides a
valid platform for the ex vivo investigation of the role of cFBs in cardiac
ischemia and fibrosis.
PMID- 28514939
TI - Antioxidant properties of drugs used in Type 2 diabetes management: could they
contribute to, confound or conceal effects of antioxidant therapy?
AB - OBJECTIVES: This is a narrative review, investigating the antioxidant properties
of drugs used in the management of diabetes, and discusses whether these
antioxidant effects contribute to, confound, or conceal the effects of
antioxidant therapy. METHODS: A systematic search for articles reporting trials,
or observational studies on the antioxidant effect of drugs used in the treatment
of diabetes in humans or animals was performed using Web of Science, PubMed, and
Ovid. Data were extracted, including data on a number of subjects, type of
treatment (and duration) received, and primary and secondary outcomes. The
primary outcomes were reporting on changes in biomarkers of antioxidants
concentrations and secondary outcomes were reporting on changes in biomarkers of
oxidative stress. RESULTS: Diabetes Mellitus is a disease characterized by
increased oxidative stress. It is often accompanied by a spectrum of other
metabolic disturbances, including elevated plasma lipids, elevated uric acid,
hypertension, endothelial dysfunction, and central obesity. This review shows
evidence that some of the drugs in diabetes management have both in vivo and in
vitro antioxidant properties through mechanisms such as scavenging free radicals
and upregulating antioxidant gene expression. CONCLUSION: Pharmaceutical agents
used in the treatment of type 2 diabetes has been shown to exert an antioxidant
effect..
PMID- 28514940
TI - The effect of initial teaching on evaluation of left ventricular volumes by
cardiovascular magnetic resonance imaging: comparison between complete and
intermediate beginners and experienced observers.
AB - BACKGROUND: High reproducibility and low intra- and interobserver variability are
important strengths of cardiac magnetic resonance (CMR). In clinical practice a
significant learning curve may however be observed. Basic CMR courses offer an
average of 1.4 h dedicated to lecturing and demonstrating left ventricular (LV)
function analysis. The purpose of this study was to evaluate the effect of
initial teaching on complete and intermediate beginners' quantitative
measurements of LV volumes and function by CMR. METHODS: Standard clinical cine
CMR sequences were acquired in 15 patients. Five observers (two complete
beginners, one intermediate, two experienced) measured LV volumes. Before initial
evaluation beginners read the SCMR guidelines on CMR analysis. After initial
evaluation, beginners participated in a two-hour teaching session including cases
and hands-on training, representative for most basic CMR courses, after which it
is uncertain to what extent different centres provide continued teaching and
feedback in-house. Dice Similarity Coefficient (DSC) assessed delineations.
Agreement, accuracy, precision, repeatability and reliability were assessed by
Bland-Altman, coefficient of variation, and intraclass correlation coefficient
methods. RESULTS: Endocardial DSC improved after teaching (+0.14 +/- 0.17;p <
0.001) for complete beginners. Low intraobserver variability was found before and
after teaching, however with wide limits of agreement. Beginners underestimated
volumes by up to 44 ml (EDV), 27 ml (ESV) and overestimated LVM by up to 53 g
before teaching, improving to an underestimation of up to 9 ml (EDV), 7 ml (ESV)
and an overestimation of up to 30 g (LVM) after teaching. For the intermediate
beginner, however, accuracy was quite high already before teaching. CONCLUSIONS:
Initial teaching to complete beginners increases accuracy for assessment of LV
volumes, however with high bias and low precision even after standardised
teaching as offered in most basic CMR courses. Even though the intermediate
beginner showed quite high accuracy already before teaching, precision did
generally not improve after standardised teaching. To maintain CMR as a technique
known for high accuracy and reproducibility and low intra- and inter-observer
variability for quantitative measurements, internationally standardised training
should be encouraged including high-quality feedback mechanisms. Objective
measurements of training methods, training duration and, above all, quality of
assessments are required.
PMID- 28514941
TI - Effects of marker density and population structure on the genomic prediction
accuracy for growth trait in Pacific white shrimp Litopenaeus vannamei.
AB - BACKGROUND: Due to the great advantages in selection accuracy and efficiency,
genomic selection (GS) has been widely studied in livestock, crop and aquatic
animals. Our previous study based on one full-sib family of Litopenaeus vannamei
(L. vannamei) showed that GS was feasible in penaeid shrimp. However, the
applicability of GS might be influenced by many factors including heritability,
marker density and population structure etc. Therefore it is necessary to
evaluate the major factors affecting the prediction ability of GS in shrimp. The
aim of this study was to evaluate the factors influencing the GS accuracy for
growth traits in L. vannamei. Genotype and phenotype data of 200 individuals from
13 full-sib families were used for this analysis. RESULTS: In the present study,
the heritability of growth traits in L. vannamei was estimated firstly based on
the full set of markers (23 K). It was 0.321 for body weight and 0.452 for body
length. The estimated heritability increased rapidly with the increase of the
marker density from 0.05 K to 3.2 K, and then it tended to be stable for both
traits. For genomic prediction on the growth traits in L. vannamei, three
statistic models (RR-BLUP, BayesA and Bayesian LASSO) showed similar performance
for the prediction accuracy of genomic estimated breeding value (GEBV). The
prediction accuracy was improved with the increasing of marker density. However,
the marker density would bring a weak effect on the prediction accuracy after the
marker number reached 3.2 K. In addition, the genetic relationship between
reference and validation population could influence the GS accuracy
significantly. A distant genetic relationship between reference and validation
population resulted in a poor performance of genomic prediction for growth traits
in L. vannamei. CONCLUSIONS: For the growth traits with moderate or high
heritability, such as body weight and body length, the number of about 3.2 K SNPs
distributed evenly along the genome was able to satisfy the need for accurate GS
prediction in the investigated L.vannamei population. The genetic relationship
between the reference population and the validation population showed significant
effects on the accuracy for genomic prediction. Therefore it is very important to
optimize the design of the reference population when applying GS to shrimp
breeding.
PMID- 28514942
TI - Corneal biomechanical properties in healthy children measured by corneal
visualization scheimpflug technology.
AB - BACKGROUND: The aim of this study was to evaluate corneal biomechanical
properties in a population of healthy children in China using corneal
visualization Scheimpflug technology (CST). METHODS: All children underwent
complete bi-ocular examinations. CST provided intraocular pressure (IOP) and
corneal biomechanical parameters, including time, velocity, length and
deformation amplitude at first applanation (A1T, A1V, A1L, A1DA), at second
applanation (A2T, A2V, A2L, A2DA), highest concavity time (HCT), maximum
deformation amplitude (MDA), peak distance (PD), and radius of curvature (RoC).
Pearson correlation analysis was used to assess the impacts of demographic
factors, central corneal thickness (CCT), spherical equivalent (SE), and IOP on
corneal biomechanics. RESULTS: One hundred eight subjects (32 girls and 76 boys)
with the mean age of 10.80 +/- 4.13 years (range 4 to18 years) were included in
the final analyses. The right and left eyes were highly symmetrical in SE (p =
0.082), IOP (p = 0.235), or CCT (p = 0.210). Mean A1T of the right eyes was 7.424
+/- 0.340 ms; the left eyes 7.451 +/- 0.365 ms. MDA was 0.993 +/- 0.102 mm in the
right eyes and 0.982 +/- 0.100 mm in the left eyes. Mean HCT of the right eyes
was 16.675 +/- 0.502 ms; the left eyes 16.735 +/- 0.555 ms. All CST parameters of
both eye were remarkably symmetrical with the exception of A2L (p = 0.006), A1DA
(p = 0.025). The majority of CST parameters of both eyes were significantly
correlated with CCT and IOP (p < 0.05). However, age, SE, and sex exert little
influence on the CST measurements. CONCLUSIONS: This study found interocular
symmetry in corneal biomechanics in healthy children eyes. Several CST
biomechanical parameters in children are modified by CCT and IOP.
PMID- 28514943
TI - Sex differences underlying orofacial varicella zoster associated pain in rats.
AB - BACKGROUND: Most people are initially infected with varicella zoster virus (VZV)
at a young age and this infection results in chickenpox. VZV then becomes latent
and reactivates later in life resulting in herpes zoster (HZ) or "shingles".
Often VZV infects neurons of the trigeminal ganglia to cause ocular problems,
orofacial disease and occasionally a chronic pain condition termed post-herpetic
neuralgia (PHN). To date, no model has been developed to study orofacial pain
related to varicella zoster. Importantly, the incidence of zoster associated pain
and PHN is known to be higher in women, although reasons for this sex difference
remain unclear. Prior to this work, no animal model was available to study these
sex-differences. Our goal was to develop an orofacial animal model for zoster
associated pain which could be utilized to study the mechanisms contributing to
this sex difference. METHODS: To develop this model VZV was injected into the
whisker pad of rats resulting in IE62 protein expression in the trigeminal
ganglia; IE62 is an immediate early gene in the VZV replication program. RESULTS:
Similar to PHN patients, rats showed retraction of neurites after VZV infection.
Treatment of rats with gabapentin, an agent often used to combat PHN, ameliorated
the pain response after whisker pad injection. Aversive behavior was
significantly greater for up to 7 weeks in VZV injected rats over control
inoculated rats. Sex differences were also seen such that ovariectomized and
intact female rats given the lower dose of VZV showed a longer affective response
than male rats. The phase of the estrous cycle also affected the aversive
response suggesting a role for sex steroids in modulating VZV pain. CONCLUSIONS:
These results suggest that this rat model can be utilized to study the mechanisms
of 1) orofacial zoster associated pain and 2) the sex differences underlying
zoster associated pain.
PMID- 28514944
TI - Short term visual outcomes of a new trifocal intraocular lens.
AB - BACKGROUND: Today, patients often expect to achieve spectacle independance after
cataract surgery. New trifocal intraocular lenses have been developed to try and
fullfill this demand. The purpose of this study is to report the short-term
visual outcomes of a new trifocal intraocular lens (AcrySof PanOptixTM). METHODS:
Consecutive adult patients undergoing cataract surgery with bilateral
implantation of the study intraocular lens in a private practice clinic were
considered for inclusion. Exclusion criteria were the presence of other ocular
pathologies or preoperative astigmatism >1.5 diopters (D). Patients with
intraoperative complications were excluded from analysis. One month after surgery
patients underwent: monocular defocus curve; monocular and binocular uncorrected
visual acuity in photopic and mesopic conditions, for far (4 m), intermediate (60
cm) and near (33 cm) distances and binocular contrast sensitivity. Patients
completed a visual satisfaction questionnaire between 9 and 12 months after
surgery. RESULTS: One hundred and sixteen eyes of fifty-eight patients receiving
bilateral implantation of the study intraocular lens were analysed. Mean
binocular uncorrected visual acuity in photopic conditions was 0.03 LogMAR for
far, 0.12 for intermediate and 0.02 for near distances. All patients achieved a
binocular uncorrected visual acuity better than 0.3 LogMAR (20/40 Snellen
equivalent) for distance and near vision and 94.8% of patients for intermediate
vision. Mesopic binocular uncorrected visual acuity values were similar to
photopic values. The monocular defocus curves showed that the best visual acuity
was reached at a vergence of 0.00D. Visual acuity dropped slightly at -1.00D and
peaked again at -2.00D. Visual acuities better than 0.2 LogMAR were maintained
between -2.50D and +0.50D. Contrast sensitivity was high and similar in photopic
and mesopic conditions. As regards patient-evaluated outcomes, only 2 patients
(3.4%) were fairly dissatisfied with their sight after surgery. Three patients
(5.1%) reported the need for spectacle correction for certain activities. All
other patients (94.8%) reported never using spectacle correction. CONCLUSIONS:
The PanOptix trifocal IOL provides good short-term visual outcomes, with good
intermediate performance and excellent patient-reported satisfaction. The similar
values achieved in mesopic and photopic conditions in binocular uncorrected
visual acuity and contrast sensitivity suggest low pupillary dependence for light
distribution. TRIAL REGISTRATION NUMBER: ISRCTN60143265 , retrospectively
registered on the 24th of April 2017.
PMID- 28514945
TI - TUmor-volume to breast-volume RAtio for improving COSmetic results in breast
cancer patients (TURACOS); a randomized controlled trial.
AB - BACKGROUND: Cosmetic result following breast conserving surgery (BCS) for cancer
influences quality of life and psychosocial functioning in breast cancer
patients. A preoperative prediction of expected cosmetic result following BCS is
not (yet) standard clinical practice and therefore the choice for either
mastectomy or BCS is still subjective. Recently, we showed that tumour volume to
breast volume ratio as well as tumour location in the breast are independent
predictors of superior cosmetic result following BCS. Implementation of a
prediction model including both factors, has not been studied in a prospective
manner. This study aims to improve cosmetic outcome by implementation of a
prediction model in the treatment decision making for breast cancer patients
opting for BCS. METHODS/DESIGN: Multicentre, single-blinded, randomized
controlled trial comparing standard preoperative work-up to a preoperative work
up with addition of the prediction model. Tumour volume to breast volume ratio
and tumour location in the breast will be used to predict cosmetic outcome in
invasive breast cancer patients opting for BCS. Three dimensional (3D)
ultrasonography will be used to measure the tumour volume to breast volume ratio
needed for the prediction model. Sample size was estimated based on a 14%
improvement in incidence of superior cosmetic result one year after BCS (71% in
the control group versus 85% in the intervention group). Primarily cosmetic
outcome will be evaluated by a 6-member independent panel. Secondary endpoints
include; (1) patient reported outcome measured by BREAST-Q, EORTC-QLQ-C30/BR23
and EQ-5D-5 L (2) cosmetic outcome as assessed through the BCCT.core software,
(3) radiation-induced reaction (4) surgical treatment performed, (5) pathological
result and (6) cost-effectiveness. Follow-up data will be collected for 3 years
after surgery or finishing radiotherapy. DISCUSSION: This randomized controlled
trial examines the value of a preoperative prediction model for the treatment
decision making. It aims for a superior cosmetic result in breast cancer patients
opting for BCS. We expect improvement of patients' quality of life and
psychosocial functioning in a cost-effective way. TRIAL REGISTRATION:
Prospectively registered, February 17th 2015, at 'Nederlands Trialregister -
NTR4997 '.
PMID- 28514946
TI - Open Questions: We don't really know anything, do we? Open questions in sensory
biology.
AB - Senses connect organisms to both the world and to each other, yet there is much
we don't know about them. Using examples drawn primarily from the author's
subfield of vision research, this article discusses five major open questions.
PMID- 28514947
TI - Enhanced chlorhexidine skin penetration with 1,8-cineole.
AB - BACKGROUND: Chlorhexidine (CHG) penetrates poorly into skin. The purpose of this
study was to compare the depth of CHG skin permeation from solutions containing
either 2% (w/v) CHG and 70% (v/v) isopropyl alcohol (IPA) or 2% (w/v) CHG, 70%
(v/v) IPA and 2% (v/v) 1,8-cineole. METHODS: An ex-vivo study using Franz
diffusion cells was carried out. Full thickness human skin was mounted onto the
cells and a CHG solution, with or without 2% (v/v) 1,8-cineole was applied to the
skin surface. After twenty-four hours the skin was sectioned horizontally in 100
MUm slices to a depth of 2000 MUm and the concentration of CHG in each section
quantified using high performance liquid chromatography (HPLC). The data were
analysed with repeated measures analysis of variance. RESULTS: The concentration
of CHG in the skin on average was significantly higher (33.3% [95%, CI 1.5% -
74.9%]) when a CHG solution which contained 1,8-cineole was applied to the skin
compared to a CHG solution which did not contain this terpene (P = 0.042).
CONCLUSIONS: Enhanced delivery of CHG can be achieved in the presence of 1,8
cineole, which is the major component of eucalyptus oil. This may reduce the
numbers of microorganisms located in the deeper layers of the skin which
potentially could decrease the risk of surgical site infection.
PMID- 28514948
TI - Demystification of animal symmetry: symmetry is a response to mechanical forces.
AB - : ?: Symmetry is an eye-catching feature of animal body plans, yet its causes are
not well enough understood. The evolution of animal form is mainly due to changes
in gene regulatory networks (GRNs). Based on theoretical considerations regarding
fundamental GRN properties, it has recently been proposed that the animal genome,
on large time scales, should be regarded as a system which can construct both the
main symmetries - radial and bilateral - simultaneously; and that the expression
of any of these depends on functional constraints. Current theories explain
biological symmetry as a pattern mostly determined by phylogenetic constraints,
and more by chance than by necessity. In contrast to this conception, I suggest
that physical effects, which in many cases act as proximate, direct, tissue
shaping factors during ontogenesis, are also the ultimate causes - i.e. the
indirect factors which provide a selective advantage - of animal symmetry, from
organs to body plan level patterns. In this respect, animal symmetry is a
necessary product of evolution. This proposition offers a parsimonious view of
symmetry as a basic feature of the animal body plan, suggesting that molecules
and physical forces act in a beautiful harmony to create symmetrical structures,
but that the concert itself is directed by the latter. REVIEWERS: This article
was reviewed by Eugene Koonin, Zoltan Varga and Michael Manuel.
PMID- 28514949
TI - Membrane of Candida albicans as a target of berberine.
AB - BACKGROUND: We investigated the mechanisms of anti-Candida action of isoquinoline
alkaloid berberine, active constituent of medically important plants of Barberry
species. METHODS: The effects on membrane, morphological transition, synthesis of
ergosterol and the consequent changes in membrane permeability have been studied.
Polarization and lipid peroxidation level of the membrane following berberine
treatment have been addressed. RESULTS: Minimal inhibitory concentration (MIC) of
berberine against C. albicans was 17.75 MUg/mL. Cytotoxic effect of berberine was
concentration dependent, and in sub-MIC concentrations inhibit morphological
transition of C. albicans cells to its filamentous form. Results showed that
berberine affects synthesis of membrane ergosterol dose-dependently and induces
increased membrane permeability causing loss of intracellular material to the
outer space (DNA/protein leakage). Berberine also caused membrane depolarization
and lipid peroxidation of membrane constituents indicating its direct effect on
the membrane. Moreover, ROS levels were also increased following berberine
treatment indicating further the possibility of membrane damage. CONCLUSION:
Based on the obtained results it seems that berberine achieves its anti-Candida
activity by affecting the cell membrane.
PMID- 28514951
TI - A computerized red glass test for quantifying diplopia.
AB - BACKGROUND: Accurate evaluation of diplopia during bedside physical examination
is challenging. We developed a new computerized red glass test (CRT) to detect,
localize, and quantify diplopia and investigated whether the CRT is useful and
feasible. METHODS: During the CRT, a white dot randomly appears on a monitor.
Because a red glass is applied on the right eye, a patient can see one white dot
and one red dot when diplopia is present. We defined the degree of diplopia as
the direct distance of the two points with the largest deviation and compared the
degree with the Hess score and Hess area ratio. RESULTS: We prospectively
enrolled 14 patients with binocular diplopia. Test-retest reliability of the CRT
was excellent (overall intraclass correlation coefficient = 0.948, 95% CI 0.939
0.956). The degree of diplopia in the CRT was well correlated with both the Hess
score (r = 0.719, p = 0.005) and the Hess area ratio (r = -0.620, p = 0.018).
CONCLUSIONS: The CRT can easily detect the presence of diplopia and provided the
quantitative values of the degree of diplopia. The CRT was useful and feasible
for improving routine bedside examination.
PMID- 28514950
TI - Lung function imaging methods in Cystic Fibrosis pulmonary disease.
AB - Monitoring of pulmonary physiology is fundamental to the clinical management of
patients with Cystic Fibrosis. The current standard clinical practise uses
spirometry to assess lung function which delivers a clinically relevant
functional readout of total lung function, however does not supply any visible or
localised information. High Resolution Computed Tomography (HRCT) is a well
established current 'gold standard' method for monitoring lung anatomical changes
in Cystic Fibrosis patients. HRCT provides excellent morphological information,
however, the X-ray radiation dose can become significant if multiple scans are
required to monitor chronic diseases such as cystic fibrosis. X-ray phase
contrast imaging is another emerging X-ray based methodology for Cystic Fibrosis
lung assessment which provides dynamic morphological and functional information,
albeit with even higher X-ray doses than HRCT. Magnetic Resonance Imaging (MRI)
is a non-ionising radiation imaging method that is garnering growing interest
among researchers and clinicians working with Cystic Fibrosis patients. Recent
advances in MRI have opened up the possibilities to observe lung function in real
time to potentially allow sensitive and accurate assessment of disease
progression. The use of hyperpolarized gas or non-contrast enhanced MRI can be
tailored to clinical needs. While MRI offers significant promise it still suffers
from poor spatial resolution and the development of an objective scoring system
especially for ventilation assessment.
PMID- 28514952
TI - Distributions and determinants of urinary biomarkers of organophosphate pesticide
exposure in a prospective Spanish birth cohort study.
AB - BACKGROUND: Prenatal exposure to organophosphate pesticides (OPs) has been
associated with impaired child development. Pesticide exposure determinants need
to be studied in order to identify sources and pathways of pesticide exposure.
The aim of this paper is to describe prenatal exposure to OPs and evaluate the
associated factors in pregnant women. METHODS: The study population consisted of
pregnant women (n = 573) who participated in the INMA birth cohort study in
Valencia (Spain, 2003-2006). OP metabolites were analyzed in maternal urine at
the 32nd week of gestation using a liquid chromatography-high resolution mass
spectrometry method. The analysis included non-specific (diethyl phosphate [DEP],
diethyl thiophosphate [DETP], dimethyl thiophosphate [DMTP], dimethyl
dithiophosphate [DMDTP]) and specific metabolites (2-diethylamino-6-methyl-4
pyrimidinol [DEAMPY], 2-isopropyl-4-methyl-6-hydroxypyrimidine [IMPY], para
nitrophenol [PNP], and 3,5,6-trichloro-2-pyridinol [TCPY]). Information about the
sociodemographic, environmental, and dietary characteristics was obtained by
questionnaire. The association between log-transformed OPs and covariates was
analyzed using multivariable interval censored regression. RESULTS: The detection
frequencies were low, DMTP and TCPY being the most frequently detected
metabolites (53.8% and 39.1%, respectively). All the OP metabolites were
positively associated with maternal intake of fruits and vegetables. Other
maternal characteristics related to the OPs were body mass index (BMI) before
pregnancy and smoking habit during pregnancy. Women with lower BMI and those who
did not smoke presented higher OP concentrations. Moreover, mothers who had a
yard or garden with plants at home or who lived in an urban area were also more
exposed to OPs. CONCLUSIONS: The OP detection frequencies and the concentrations
observed in our study population were low, compared with most of the previously
published studies. Given the high vulnerability of the fetus to neurotoxicant
exposure, further research on the determinants of the body burden of OPs during
pregnancy would be necessary. The knowledge gained from such studies would
enhance the effectiveness of public health control and future recommendations in
order to reduce the risk to both the health of pregnant women and the health and
development of their children.
PMID- 28514953
TI - Emergence of Babesia canis in southern England.
AB - BACKGROUND: The United Kingdom is considered free of autochthonous transmission
of canine babesiosis although cases are reported in dogs associated with recent
travel abroad. During the winter months of 2015/16, a cluster of cases of disease
in dogs with signs suggestive of canine babesiosis were reported in Harlow,
Essex. METHODS: Babesia species were detected in dog blood samples by Giemsa
staining of blood smears and by pan-piroplasm PCRs. Babesia species were also
detected in extracts of tick DNA using pan-piroplasm PCRs. DNA sequencing and
phylogenetic analysis was used to confirm the species of Babesia present in dog
blood and tick samples. Tick species were identified by PCR-sequencing based on
amplification of the cytochrome c oxidase subunit one (cox1) gene. Dermacentor
reticulatus ticks were sampled from field sites in England and Wales. RESULTS:
Blood smear analysis on samples taken from some of the affected dogs confirmed
the presence of a large Babesia species within erythrocytes. A tick recovered
from one of these cases was identified as Dermacentor reticulatus, a species with
a limited distribution in England and Wales, but a known vector of canine
babesiosis in continental Europe. Babesia canis was subsequently identified in
blood samples obtained from three clinical cases (all dogs) within the area and
from ticks associated with these dogs. A field survey detected 17 adult D.
reticulatus ticks from one area visited by the affected dogs. Fourteen of these
ticks were shown to be positive for the B. canis parasite, implicating them as a
potential source for babesiosis in Harlow. In order to assess whether the
parasite is present in more than one tick population, D. reticulatus ticks from
across England and Wales were screened for the presence of Babesia species. In
addition to the Harlow site, a further five locations where D. reticulatus is
present were screened for Babesia species. Babesia was not detected from most
sites tested but one tick from a single location in Wales was positive for B.
canis. CONCLUSIONS: Infection with B. canis was confirmed in a number of dogs in
Harlow, Essex, with no history of travel outside of the country. The same
pathogen was identified in field-caught D. reticulatus ticks in the same area and
is considered the likely source of infection. This highlights the need for
vigilance by veterinary surgeons for future outbreaks of tick-borne disease in
dogs.
PMID- 28514955
TI - Label-free biosensing of Salmonella enterica serovars at single-cell level.
AB - BACKGROUND: The emerging nanotechnologies have greatly facilitated the
development of label-free biosensors. The atomic force microscopy (AFM) has been
used to study the molecular mechanism of the reactions for protein and aptamers.
The surface plasmon resonance (SPR) have been used in fast detections of various
pathogens such as bacteria. This study used both AFM and SPR to investigate the
complex reactions between aptamers and outer membrane proteins (OMPs) on the
surface of S. typhimurium. RESULTS: Two DNA aptamers were used for the label-free
detections of S. typhimurium by AFM and SPR. The aptamers have specific binding
affinities to the OMPs of S. typhimurium. At single-molecule level, the high
resolution AFM topography and recognition images distinguished the OMPs on the
bacteria surface, which is the first time the location of individual outer
membrane protein have been determined on Salmonella surface. E. coli in the
control experiments didn't generate recognition signals, which proved the
specificity of these two aptamers to S. typhimurium. The off-rate values for the
interactions of these two aptamers to the OMPs were estimated as 5.2 * 10-3 and
7.4 * 10-3 s-1, respectively, by the AFM dynamic force microscopy (DFS). The
force and extension values form DFS measurements were used to distinguish the two
aptamers. The surface membrane model was proposed to explain the complex
correlations among force and extension values. Next, these two aptamers were used
in the bulk solution detections of S. typhimurium. The gold chips in SPR
experiments were modified with carboxymethylated-dextran (CD), followed by
aptamers immobilization, to reduce the non-specific binding signals. The limit of
detection (LOD) was determined as 3 * 104 CFU mL-1. CONCLUSIONS: The AFM single
molecule study revealed detailed information about the unbinding force and
extension of the aptamer in complex biological reactions. The careful analysis of
the experimental results provide better understanding of the molecular mechanism
of OMPs reactions. The single-molecule measurements are helpful in evaluating the
specificity of binding reagents, such as aptamers, in bulk solution detections.
The protocols used in the SPR detections can be expanded into the label-free
detections of other bacterial pathogens.
PMID- 28514954
TI - Needle exchange programs for the prevention of hepatitis C virus infection in
people who inject drugs: a systematic review with meta-analysis.
AB - BACKGROUND: Previous research on the effectiveness of needle exchange programs
(NEP) in preventing hepatitis C virus (HCV) in people who inject drugs (PWID) has
shown mixed findings. The purpose of this study was to use the meta-analytic
approach to examine the association between NEP use and HCV prevention in PWIDs.
METHODS: Study inclusion criteria were (1) observational studies, (2) PWIDs, (3)
NEP use, (4) HCV status ascertained by serological testing, (5) studies published
in any language since January 1, 1989, and (6) data available for measures of
association. Studies were located by searching four electronic databases and
cross-referencing. Study quality was assessed using the Newcastle Ottawa (NOS)
scale. A ratio measure of association was calculated for each result from cohort
or case-control studies and pooled using a random effects model. Odds ratio (OR)
and hazard ratio (HR) models were analyzed separately. Results were considered
statistically significant if the 95% confidence interval (CI) did not cross 1.
Heterogeneity was estimated using Q and I 2 with alpha values for Q <= 0.10
considered statistically significant. RESULTS: Of the 555 citations reviewed, 6
studies containing 2437 participants were included. Studies had an average NOS
score of 7 out of 9 (77.8%) stars. Concerns over participant representativeness,
unclear adjustments for confounders, and bias from participant nonresponse and
loss to follow-up were noted. Results were mixed with the odds ratio model
indicating no consistent association (OR, 0.51, 95% CI, 0.05-5.15), and the
hazard ratio model indicating a harmful effect (HR, 2.05, 95% CI, 1.39-3.03).
Substantial heterogeneity (p <= 0.10) and moderate to large inconsistency (I 2
>= 66%) were observed for both models. CONCLUSIONS: The impact of NEPs on HCV
prevention in PWIDs remains unclear. There is a need for well-designed research
studies employing standardized criteria and measurements to clarify this issue.
TRIAL REGISTRATION: PROSPERO CRD42016035315.
PMID- 28514956
TI - Transcriptome analysis for the identification of cellular markers related to
trabecular meshwork differentiation.
AB - BACKGROUND: Development of primary open-angle glaucoma (POAG) is associated with
the malfunctioning trabecular meshwork (TM). Cell therapy offers great potential
for the treatment of POAG, but requires the generation of functional TM cells in
vitro to replace the lost/dysfunctional cells. TM differentiation in vitro from
various stem cell types must be monitored by the expression of specific markers.
However, no single definitive marker of the TM has been identified. RESULTS: To
identify robust markers of TM differentiation, we performed global transcriptome
profiling using high-density oligonucleotide microarray on ex vivo TM tissue and
cultured TM progenitors. Corneal and scleral tissues were also used in the
analysis. After removal of genes expressed in the cornea and sclera, 18 genes
were identified that were differentially expressed in the TM relative to the
other samples. CDH23, F5, KCNAB1, FGF9, SPP1, and HEY1 were selected among the
genes highly expressed in the TM, together with BDNF which was repressed,
compared to progenitors for further investigation. Expression analysis by qPCR
verified the differential expression and immunofluorescence of the anterior
segment confirmed strong expression in the TM. CONCLUSIONS: Three independent
cohort of expression studies have identified novel markers, fitting in
identifying TM cells and in evaluating directed TM differentiation in vitro.
PMID- 28514957
TI - High lymphatic vessel density and presence of lymphovascular invasion both
predict poor prognosis in breast cancer.
AB - BACKGROUND: Lymphatic vessel density and lymphovascular invasion are commonly
assessed to identify the clinicopathological outcomes in breast cancer. However,
the prognostic values of them on patients' survival are still uncertain. METHODS:
Databases of PubMed, Embase, and Web of Science were searched from inception up
to 30 June 2016. The hazard ratio with its 95% confidence interval was used to
determine the prognostic effects of lymphatic vessel density and lymphovascular
invasion on disease-free survival and overall survival in breast cancer. RESULTS:
Nineteen studies, involving 4215 participants, were included in this study. With
the combination of the results of lymphatic vessel density, the pooled hazard
ratios and 95% confidence intervals were 2.02 (1.69-2.40) for disease-free
survival and 2.88 (2.07-4.01) for overall survival, respectively. For
lymphovascular invasion study, the pooled hazard ratios and 95% confidence
intervals were 1.81 (1.57-2.08) for disease-free survival and 1.64 (1.43-1.87)
for overall survival, respectively. In addition, 29.56% (827/2798) of
participants presented with lymphovascular invasion in total. CONCLUSIONS: Our
study demonstrates that lymphatic vessel density and lymphovascular invasion can
predict poor prognosis in breast cancer. Standardized assessments of lymphatic
vessel density and lymphovascular invasion are needed.
PMID- 28514958
TI - Neonatal respiratory morbidity following exposure to chorioamnionitis.
AB - BACKGROUND: There are conflicting results in the literature on the impact of
chorioamnionitis on neonatal respiratory morbidities. However, most studies are
based on small clinical samples and fail to account for the competing risk of
perinatal death. This study aimed to determine whether chorioamnionitis affects
the incidence of respiratory distress syndrome (RDS) and bronchopulmonary
dysplasia (BPD) after accounting for the increased risk of death. METHODS:
Retrospective cohort study using linked birth and infant death registration and
hospitalization records from Washington State between 2002 and 2011 (n = 763,671
singleton infants and n = 56,537 singleton preterm infants). Logistic regression
models based on the traditional and fetuses-at-risk approaches were used to model
two composite outcomes namely RDS and perinatal death and BPD and perinatal
death. Confounders adjusted for in the models included maternal age, race,
diabetes, hypertension, antenatal corticosteroids, mode of delivery and infant
sex. RESULTS: While models using the traditional approach found a significant
association only between chorioamnionitis and composite BPD and perinatal death
(OR = 1.23, 95% CI: 1.01-1.50); using the fetuses-at-risk approach, there was a
significant association between chorioamnionitis and both composite outcomes (RDS
and perinatal death OR = 2.74, 2.50-3.01; BPD and perinatal death OR = 5.18, 95%
CI: 4.39-6.11). CONCLUSION: The fetuses-at-risk approach models the causal impact
of chorioamnionitis on the development of the fetal lung and shows an increased
risk of RDS, BPD and perinatal death associated with such maternal infection.
PMID- 28514960
TI - Segmental testicular infarction: a case report.
AB - BACKGROUND: Segmental testicular infarction is a very rare condition, which can
mimic a testicular torsion or testicular cancer. Correct diagnosis is difficult
but it is important to avoid unnecessary radical treatment. CASE PRESENTATION: We
report a clinical case of a 36-year-old white man who presented at our emergency
department with subacute testicular pain. A urine analysis, Doppler ultrasound,
surgical exploration, blood analysis, and magnetic resonance imaging were
performed to diagnose his condition, to exclude a testicular torsion, and to
raise confidence in its non-malignancy. He was treated conservatively. At follow
up, a few months after the incident, he no longer had complaints. Ultrasonography
showed remaining hypo-echogenicity of the left upper pole, indicating a sequel of
ischemia. CONCLUSIONS: Segmental testicular infarction is a rare condition which
can be easily confused with a testicular torsion or a testicular tumor. This case
report can be helpful in recognizing and diagnosing this condition. Making the
right diagnosis is important since it can prevent an unnecessary radical
treatment.
PMID- 28514959
TI - Prevention of postpartum haemorrhage by community-based auxiliary midwives in
hard-to-reach areas of Myanmar: a qualitative inquiry into acceptability and
feasibility of task shifting.
AB - BACKGROUND: In Myanmar, postpartum haemorrhage is the leading cause of maternal
mortality and contributes to around 30% of all maternal deaths. The World Health
Organization recommends training and supporting auxiliary midwives to administer
oral misoprostol for prevention of postpartum haemorrhage in resource-limited
settings. However, use of misoprostol by auxiliary midwives has not formally been
approved in Myanmar. Our study aimed to explore community and provider
perspectives on the roles of auxiliary midwives and community-level provision of
oral misoprostol by auxiliary midwives. METHODS: A qualitative inquiry was
conducted in Ngape Township, Myanmar. A total of 15 focus group discussions with
midwives, auxiliary midwives, community members and mothers with children under
the age of three were conducted. Ten key informant interviews were performed with
national, district and township level health planners and implementers of
maternal and child health services. All audio recordings were transcribed
verbatim in Myanmar language. Transcripts of focus group discussions were fully
translated into English before coding, while key informants' data were coded in
Myanmar language. Thematic analysis was done using ATLAS.ti software. RESULTS:
Home births are common and auxiliary midwives were perceived as an essential care
provider during childbirth in hard-to-reach areas. Main reasons provided were
that auxiliary midwives are more accessible than midwives, live in the hard-to
reach areas, and are integrated in the community and well connected with
midwives. Auxiliary midwives generally reported that their training involved
instruction on active management of the third stage of labour, including use of
misoprostol, but not all auxiliary midwives reported using misoprostol in
practice. Supportive reasons for task-shifting administration of oral misoprostol
to auxiliary midwives included discussions around the good relationship and trust
between auxiliary midwives and midwives, whereby midwives felt confident
distributing misoprostol to auxiliary midwives. However, the lack of clear
government-level written permission to distribute the drug was perceived as a
barrier to task shifting. CONCLUSION: This study highlights the acceptability of
misoprostol use by auxiliary midwives to prevent postpartum haemorrhage, and
findings suggest that it should be considered as a promising intervention for
task shifting in Myanmar.
PMID- 28514961
TI - How many people will need palliative care in 2040? Past trends, future
projections and implications for services.
AB - BACKGROUND: Current estimates suggest that approximately 75% of people
approaching the end-of-life may benefit from palliative care. The growing numbers
of older people and increasing prevalence of chronic illness in many countries
mean that more people may benefit from palliative care in the future, but this
has not been quantified. The present study aims to estimate future population
palliative care need in two high-income countries. METHODS: We used mortality
statistics for England and Wales from 2006 to 2014. Building on previous
diagnosis-based approaches, we calculated age- and sex-specific proportions of
deaths from defined chronic progressive illnesses to estimate the prevalence of
palliative care need in the population. We calculated annual change over the 9
year period. Using explicit assumptions about change in disease prevalence over
time, and official mortality forecasts, we modelled palliative care need up to
2040. We also undertook separate projections for dementia, cancer and organ
failure. RESULTS: By 2040, annual deaths in England and Wales are projected to
rise by 25.4% (from 501,424 in 2014 to 628,659). If age- and sex-specific
proportions with palliative care needs remain the same as in 2014, the number of
people requiring palliative care will grow by 25.0% (from 375,398 to 469,305
people/year). However, if the upward trend observed from 2006 to 2014 continues,
the increase will be of 42.4% (161,842 more people/year, total 537,240). In
addition, disease-specific projections show that dementia (increase from 59,199
to 219,409 deaths/year by 2040) and cancer (increase from 143,638 to 208,636
deaths by 2040) will be the main drivers of increased need. CONCLUSIONS: If
recent mortality trends continue, 160,000 more people in England and Wales will
need palliative care by 2040. Healthcare systems must now start to adapt to the
age-related growth in deaths from chronic illness, by focusing on integration and
boosting of palliative care across health and social care disciplines. Countries
with similar demographic and disease changes will likely experience comparable
rises in need.
PMID- 28514962
TI - Revisiting annual screening for latent tuberculosis infection in healthcare
workers: a cost-effectiveness analysis.
AB - BACKGROUND: In North America, tuberculosis incidence is now very low and risk to
healthcare workers has fallen. Indeed, recent cohort data question routine annual
tuberculosis screening in this context. We compared the cost-effectiveness of
three potential strategies for ongoing screening of North American healthcare
workers at risk of exposure. The analysis did not evaluate the cost-effectiveness
of screening at hiring, and considered only workers with negative baseline tests.
METHODS: A decision analysis model simulated a hypothetical cohort of 1000
workers following negative baseline tests, considering duties, tuberculosis
exposure, testing and treatment. Two tests were modelled, the tuberculin skin
test (TST) and QuantiFERON(r)-TB-Gold In-Tube (QFT). Three screening strategies
were compared: (1) annual screening, where workers were tested yearly; (2)
targeted screening, where workers with high-risk duties (e.g. respiratory
therapy) were tested yearly and other workers only after recognised exposure; and
(3) post exposure-only screening, where all workers were tested only after
recognised exposure. Workers with high-risk duties had 1% annual risk of
infection, while workers with standard patient care duties had 0.3%. In an
alternate higher-risk scenario, the corresponding annual risks of infection were
3% and 1%, respectively. We projected costs, morbidity, quality-adjusted survival
and mortality over 20 years after hiring. The analysis used the healthcare system
perspective and a 3% annual discount rate. RESULTS: Over 20 years, annual
screening with TST yielded an expected 2.68 active tuberculosis cases/1000
workers, versus 2.83 for targeted screening and 3.03 for post-exposure screening
only. In all cases, annual screening was associated with poorer quality-adjusted
survival, i.e. lost quality-adjusted life years, compared to targeted or post
exposure screening only. The annual TST screening strategy yielded an incremental
cost estimate of $1,717,539 per additional case prevented versus targeted TST
screening, which in turn cost an incremental $426,678 per additional case
prevented versus post-exposure TST screening only. With the alternate "higher
risk" scenario, the annual TST strategy cost an estimated $426,678 per additional
case prevented versus the targeted TST strategy, which cost an estimated $52,552
per additional case prevented versus post-exposure TST screening only. In all
cases, QFT was more expensive than TST, with no or limited added benefit.
Sensitivity analysis suggested that, even with limited exposure recognition,
annual screening was poorly cost-effective. CONCLUSIONS: For most North American
healthcare workers, annual tuberculosis screening appears poorly cost-effective.
Reconsideration of screening practices is warranted.
PMID- 28514965
TI - Drug-based vector control: a potential new paradigm.
PMID- 28514964
TI - HELP! Problems in executing a pragmatic, randomized, stepped wedge trial on the
Hospital Elder Life Program to prevent delirium in older patients.
AB - BACKGROUND: A pragmatic, stepped wedge trial design can be an appealing design to
evaluate complex interventions in real-life settings. However, there are certain
pitfalls that need to be considered. This paper reports on the experiences and
lessons learned from the conduct of a cluster randomized, stepped wedge trial
evaluating the effect of the Hospital Elder Life Program (HELP) in a Dutch
hospital setting to prevent older patients from developing delirium. METHODS: We
evaluated our trial which was conducted in eight departments in two hospitals in
hospitalized patients aged 70 years or older who were at risk for delirium by
reflecting on the assumptions that we had and on what we intended to accomplish
when we started, as compared to what we actually realized in the different phases
of our study. Lessons learned on the design, the timeline, the enrollment of
eligible patients and the use of routinely collected data are provided
accompanied by recommendations to address challenges. RESULTS: The start of the
trial was delayed which caused subsequent time schedule problems. The requirement
for individual informed consent for a quality improvement project made the
inclusion more prone to selection bias. Most units experienced major difficulties
in including patients, leading to excluding two of the eight units from
participation. This resulted in failing to include a similar number of patients
in the control condition versus the intervention condition. Data on outcomes
routinely collected in the electronic patient records were not accessible during
the study, and appeared to be often missing during analyses. CONCLUSIONS: The
stepped wedge, cluster randomized trial poses specific risks in the design and
execution of research in real-life settings of which researchers should be aware
to prevent negative consequences impacting the validity of their results. Valid
conclusions on the effectiveness of the HELP in the Dutch hospital setting are
hampered by the limited quantity and quality of routine clinical data in our
pragmatic trial. Executing a stepped wedge design in a daily practice setting
using routinely collected data requires specific attention to ethical review,
flexibility, a spacious time schedule, the availability of substantial capacity
in the research team and early checks on the data availability and quality. TRIAL
REGISTRATION: Netherlands Trial Register, identifier: NTR3842 . Registered on 24
January 2013.
PMID- 28514963
TI - Patient-centered primary care for adults at high risk for AUDs: the Choosing
Healthier Drinking Options In primary CarE (CHOICE) trial.
AB - BACKGROUND: Most patients with alcohol use disorders (AUDs) never receive alcohol
treatment, and experts have recommended management of AUDs in primary care. The
Choosing Healthier Drinking Options In primary CarE (CHOICE) trial was a
randomized controlled effectiveness trial of a novel intervention for primary
care patients at high risk for AUDs. This report describes the conceptual and
scientific foundation of the CHOICE model of care, critical elements of the
CHOICE trial design consistent with the Template for Intervention Description and
Replication (TIDieR), results of recruitment, and baseline characteristics of the
enrolled sample. METHODS: The CHOICE intervention is a multi-contact, extended
counseling intervention, based on the Chronic Care Model, shared decision-making,
motivational interviewing, and evidence-based options for managing AUDs, designed
to be practical in primary care. Outpatients who received care at 3 Veterans
Affairs primary care sites in the Pacific Northwest and reported frequent heavy
drinking (>=4 drinks/day for women; >=5 for men) were recruited (2011-2014) into
a trial in which half of the participants would be offered additional alcohol
related care from a nurse. CHOICE nurses offered 12 months of patient-centered
care, including proactive outreach and engagement, repeated brief motivational
interventions, monitoring with and without alcohol biomarkers, medications for
AUDs, and/or specialty alcohol treatment as appropriate and per patient
preference. A CHOICE nurse practitioner was available to prescribe medications
for AUDs. RESULTS: A total of 304 patients consented to participate in the CHOICE
trial. Among consenting participants, 90% were men, the mean age was 51 (range 22
75), and most met DSM-IV criteria for alcohol abuse (14%) or dependence (59%).
Many participants also screened positive for tobacco use (44%), depression (45%),
anxiety disorders (30-41%) and non-tobacco drug use disorders (19%). At baseline,
participants had a median AUDIT score of 18 [Interquartile range (IQR) 14-24] and
a median readiness to change drinking score of 5 (IQR 2.75-6.25) on a 1-10 Likert
scale. CONCLUSION: The CHOICE trial tested a patient-centered intervention for
AUDs and recruited primary care patients at high risk for AUDs, with a spectrum
of severity, co-morbidity, and readiness to change drinking. Trial registration
The trial is registered at clinicaltrial.gov (NCT01400581).
PMID- 28514966
TI - Clinical applications of PD-L1 bioassays for cancer immunotherapy.
AB - Programmed death ligand 1 (PD-L1) has emerged as a biomarker that can help to
predict responses to immunotherapies targeted against PD-L1 and its receptor (PD
1). Companion tests for evaluating PD-L1 expression as a biomarker of response
have been developed for many cancer immunotherapy agents. These assays use a
variety of detection platforms at different levels (protein, mRNA), employ
diverse biopsy and surgical samples, and have disparate positivity cutoff points
and scoring systems, all of which complicate the standardization of clinical
decision-making. This review summarizes the current understanding and ongoing
investigations regarding PD-L1 expression as a potential biomarker for clinical
outcomes of anti-PD-1/PD-L1 immunotherapy.
PMID- 28514967
TI - AT1-receptor response to non-saturating Ang-II concentrations is amplified by
calcium channel blockers.
AB - BACKGROUND: Blockers of angiotensin II type 1 receptor (AT1R) and the voltage
gated calcium channel 1.2 (CaV1.2) are commonly used for treatment of
hypertension. Yet there is little information about the effect of physiological
concentrations of angiotensin II (AngII) on AT1R signaling and whether there is a
reciprocal regulation of AT1R signaling by CaV1.2. METHODS: To elucidate these
questions, we have studied the Ca2+ signaling response to physiological and
pharmacological AngII doses in HEK293a cells, vascular smooth muscle cells and
cardiomyocytes using a Ca2+ sensitive dye as the principal sensor. Intra-cellular
calcium recordings were performed in presence and absence of CaV1.2 blockers.
Semi-quantitative imaging methods were used to assess the plasma membrane
expression of AT1R and G-protein activation. RESULTS: Repeated exposure to
pharmacological (100 nM) concentrations of AngII caused, as expected, a down
regulation of the Ca2+ response. In contrast, repeated exposure to physiological
(1 nM) AngII concentration resulted in an enhancement of the Ca2+ response. The
up-regulation of the Ca2+ response to repeated 1 nM AngII doses and the down
regulation of the Ca2+ response to repeated 100 nM Angll doses were not
accompanied by a parallel change of the AT1R plasma membrane expression. The Ca2+
response to 1 nM of AngII was amplified in the presence of therapeutic
concentrations of the CaV1.2 blockers, nifedipine and verapamil, in vascular
smooth muscle cells, cardiomyocytes and HEK293a cells. Amplification of the AT1R
response was also observed following inhibition of the calcium permeable
transient receptor potential cation channels, suggesting that the activity of
AT1R is sensitive to calcium influx. CONCLUSIONS: Our findings have implications
for the understanding of hyperactivity of the angiotensin system and for use of
Ca2+ channel blockers as mono-therapy in hypertension.
PMID- 28514968
TI - Further evaluation of the NWF filter for the purification of Plasmodium vivax
infected erythrocytes.
AB - BACKGROUND: Isolation of Plasmodium-infected red blood cells (iRBCs) from
clinical blood samples is often required for experiments, such as ex vivo drug
assays, in vitro invasion assays and genome sequencing. Current methods for
removing white blood cells (WBCs) from malaria-infected blood are time-consuming
or costly. A prototype non-woven fabric (NWF) filter was developed for the
purification of iRBCs, which showed great efficiency for removing WBCs in a pilot
study. Previous work was performed with prototype filters optimized for
processing 5-10 mL of blood. With the commercialization of the filters, this
study aims to evaluate the efficiency and suitability of the commercial NWF
filter for the purification of Plasmodium vivax-infected RBCs in smaller volumes
of blood and to compare its performance with that of Plasmodipur(r) filters.
METHODS: Forty-three clinical P. vivax blood samples taken from symptomatic
patients attending malaria clinics at the China-Myanmar border were processed
using the NWF filters in a nearby field laboratory. The numbers of WBCs and iRBCs
and morphology of P. vivax parasites in the blood samples before and after NWF
filtration were compared. The viability of P. vivax parasites after filtration
from 27 blood samples was examined by in vitro short-term culture. In addition,
the effectiveness of the NWF filter for removing WBCs was compared with that of
the Plasmodipur(r) filter in six P. vivax blood samples. RESULTS: Filtration of 1
2 mL of P. vivax-infected blood with the NWF filter removed 99.68% WBCs. The
densities of total iRBCs, ring and trophozoite stages before and after filtration
were not significantly different (P > 0.05). However, the recovery rates of
schizont- and gametocyte-infected RBCs, which were minor parasite stages in the
clinical samples, were relatively low. After filtration, the P. vivax parasites
did not show apparent morphological changes. Culture of 27 P. vivax-infected
blood samples after filtration showed that parasites successfully matured into
the schizont stage. The WBC removal rates and iRBC recovery rates were not
significantly different between the NWF and Plasmodipur(r) filters (P > 0.05).
CONCLUSIONS: When tested with 1-2 mL of P. vivax-infected blood, the NWF filter
could effectively remove WBCs and the recovery rates for ring- and trophozoite
iRBCs were high. P. vivax parasites after filtration could be successfully
cultured in vitro to reach maturity. The performance of the NWF and
Plasmodipur(r) filters for removing WBCs and recovering iRBCs was comparable.
PMID- 28514969
TI - Endothelial progenitor cell number is not decreased in 34 children with Juvenile
Dermatomyositis: a pilot study.
AB - OBJECTIVE: A pilot study to determine endothelial progenitor cells (EPC) number
in children with Juvenile Dermatomyositis (JDM). METHODS: After obtaining
informed consent, the EPC number from 34 fasting children with definite/probable
JDM at various stages of therapy-initially untreated, active disease on
medication and clinically inactive, off medication-was compared with 13 healthy
fasting pediatric controls. The EPC number was determined by fluorescence
activated cell sorting (FACS), CD34+/VEGFR2+/CD45dim-, and assessed in
conjunction with clinical variables: disease activity scores (DAS), duration of
untreated disease (DUD), TNF-alpha allelic polymorphism (A/G) at the promoter
region of -308, number of nailfold capillary end row loop (ERL) and von
Willebrand factor antigen (vWF:Ag). Correlations of the EPC numbers with the
clinical and demographic variables, including DAS Skin (DAS SK), DAS Weakness
(DAS WK), DAS Total Score, DUD, Cholesterol, triglycerides, High-Density
Lipoprotein (HDL) and Low-Density Lipoprotein (LDL), and ERL were calculated
using the Pearson correlation coefficient. Tests of associations of EPC with
gender (boy vs girl), TNF-alpha-308A allele (GA/AA vs GG), vWF:Ag (categorized by
specific ABO type) as normal/abnormal were performed, using two-sample T- tests.
RESULTS: The EPC number for JDM was not significantly different from the healthy
controls and was not associated with any of the clinical or cardiovascular risk
factors tested. CONCLUSION: The EPC for JDM were in the normal range, similar to
adults with DM. These data support the concept that the normal EPC numbers in
DM/JDM, irrespective of age, differs from adult PM, where they are decreased,
perhaps reflecting a different pathophysiology.
PMID- 28514970
TI - Transmission of ST8-USA300 Latin American Variant Methicillin-Resistant
Staphylococcus aureus on a Neonatal Intensive Care Unit: Recurrent Skin and Soft-
Tissue Infections as a Marker for Epidemic Community-Associated-MRSA
Colonization.
PMID- 28514971
TI - Effects of organic complexed or inorganic Co, Cu, Mn and Zn supplementation
during a 45-day preconditioning period on productive and health responses of
feeder cattle.
AB - This experiment evaluated production and health parameters among cattle offered
concentrates containing inorganic or organic complexed sources of supplemental
Cu, Co, Mn and Zn during a 45-day preconditioning period. In total, 90
Angus*Hereford calves were weaned at 7 months (day -1), sorted by sex, weaning BW
and age (261+/-2 kg; 224+/-2 days), and allocated to 18 drylot pens (one heifer
and four steers per pen) on day 0; thus, all pens had equivalent initial BW and
age. Pens were randomly assigned to receive a corn-based preconditioning
concentrate containing: (1) Cu, Co, Mn and Zn sulfate sources (INR), (2) Cu, Mn,
Co and Zn complexed organic source (AAC) or (3) no Cu, Co, Mn and Zn
supplementation (CON). From day 0 to 45, cattle received concentrate treatments
(2.7 kg/animal daily, as-fed basis) and had free-choice access to orchardgrass
(Dactylis glomerata L.), long-stem hay and water. The INR and AAC treatments were
formulated to provide the same daily amount of Co, Cu, Mn and Zn at a 50-, 16-, 8
and ninefold increase, respectively, compared with the CON treatment. On day 46,
cattle were transported to a commercial feedlot, maintained as a single pen, and
offered a free-choice receiving diet until day 103. Calf full BW was recorded on
days -1 and 0, 45 and 46, and 102 and 103 for average daily gain (ADG)
calculation. Liver biopsy was performed on days 0 (used as covariate), 22 and 45.
Cattle were vaccinated against respiratory pathogens on days 15, 29 and 46. Blood
samples were collected on days 15, 29, 45, 47, 49, 53 and 60. During
preconditioning, mean liver concentrations of Co, Zn and Cu were greater (P?0.03)
in AAC and INR compared with CON. No treatment effects were detected (P?0.17) for
preconditioning feed intake, ADG or feed efficiency. No treatment effects were
detected (P?0.48) for plasma concentrations of antibodies against Mannheimia
haemolytica, bovine viral diarrhea types 1 and 2 viruses. Plasma haptoglobin
concentrations were similar among treatments (P=0.98). Mean plasma cortisol
concentration was greater (P?0.04) in CON compared with INR and AAC. No treatment
effects were detected (P?0.37) for cattle ADG during feedlot receiving. Hence,
INR and AAC increased liver concentrations of Co, Zn and Cu through
preconditioning, but did not impact cattle performance and immunity responses
during preconditioning and feedlot receiving.
PMID- 28514972
TI - The effect of Tetraneura ulmi L. galling process on the activity of amino acid
decarboxylases and the content of biogenic amines in Siberian elm tissues.
AB - Tetraneura ulmi (L.), a member of Eriosomatinae subfamily, is one of the gall
forming aphids occurring on elms. Sap-sucking behaviour of founding mothers
results in the formation of new plant organs. This study documents the changes in
the content of plant biogenic amines (putrescine, cadaverine, spermidine,
tryptamine, spermine and histamine) and key enzymes of their biosynthesis: lysine
decarboxylase (LDC), tyrosine decarboxylase and ornithine decarboxylase (ODC) in
galls and other parts of Siberian elm (Ulmus pumila L.) leaves during the galling
process. The direction and intensity of these changes for particular amines and
enzymes were dependent on the stage of gall development and part of the galling
leaf. Generally, the amine content tended to increase in gall tissues during the
1st and 2nd period of the galling process and decreased in later phases. LDC and
ODC activities were markedly enhanced, especially in gall tissues at the initial
stage of the galling process.
PMID- 28514973
TI - Olfactory evaluation of boar taint: effect of factors measured at slaughter and
link with boar taint compounds.
AB - There is a commitment by the European pig sector to ban surgical castration of
male piglets in the European Union in 2018. One alternative to castration is to
raise entire male pigs, with an increased risk of boar taint. A field study was
performed to: (1) evaluate inter- and intra-farm variation in boar taint
prevalence, (2) investigate factors measured at slaughter influencing boar taint
and (3) evaluate the relationship between sensorial scoring by a trained panel
and the concentration of boar taint components. From 34 farms, neck fat samples
were collected from all entire male pigs in at least two slaughter batches per
farm (78 batches; 9167 animals). In addition to olfactory boar taint analysis,
data were also collected on fresh skin lesions (score 0 to 3) at the slaughter
line, slaughter weight, lean meat percentage, duration of transport, time spent
in lairage, total delivery duration, day length, shortening of days and outdoor
mean temperature. Using the hot iron method, neck fat samples were scored (eight
point scale) for boar taint. Average boar taint prevalence (score >=3) was 5.6+/
2.5% and the mean difference between the maximum and minimum prevalence per farm
was 4.3+/-3.2%. Androstenone (AND), skatole (SKA) and indole concentrations were
measured for a subset (n=254) of the samples. According to binomial univariate
mixed models, entire male pigs with a higher skin lesion score had higher odds of
having boar taint (P=0.031), as did fatter entire male pigs (P<0.001). In the
binomial multivariate mixed model lean meat percentage (P<0.001) and outdoor mean
temperature (P=0.005) remained as only significant factors. Based on our results,
we can conclude that these statistically significant at least partially influence
the prevalence of boar taint. According to the binomial univariate mixed models
SKA concentration in liquid fat seems a better predictor for boar taint than AND.
There were no significant synergetic effects between boar taint compounds.
PMID- 28514974
TI - Additional thoughts on teaching and prescribing MAOIs.
PMID- 28514975
TI - Courttney Cooper: mapping the interior.
PMID- 28514976
TI - Working Despite Having Influenza-Like Illness: Results of An Anonymous Survey of
Healthcare Providers Who Care for Transplant Recipients.
AB - OBJECTIVE To compare the rates of and reasons for presenteeism associated with
influenza-like illness (ILI) among healthcare professionals (HCPs) caring for
hospitalized inpatient transplant recipients and internal medicine patients.
DESIGN We designed a 10-question anonymous survey in which ILI was defined as
fever (>37.8 degrees C) and cough and/or sore throat and ILI B was defined as
fever (>37.8 degrees C) or cough or sore throat; both definitions were considered
in the absence of another known cause. SETTING Tertiary-care center. PARTICIPANTS
Physicians, advanced practice providers (APPs) and nurses. INTERVENTION Survey
deployed at peak of influenza activity in 2016. MEASUREMENTS Rates of ILI,
presenteeism, wearing masks, and time away due to ILI. RESULTS Of 707 HCPs
surveyed, 286 (40%) responded; 15 (5.2%) reported having ILI, and 73 (25.5%)
reported having ILI B in the preceding 2 weeks. Presenteeism rates were 92% in
both groups of HCPs and were higher among women (adjusted odds ratio [AOR], 2.64;
95% CI, 1.23-5.71; P=.01) and those <=40 years old (AOR, 1.92; 95% CI, 1.03-3.68;
P=.04). Healthcare professionals who cared for transplant recipients and female
HCPs were more likely to wear masks (AOR, 2.13; 95% CI, 1.05-3.40; P=.04 for
transplant recipients and AOR, 3.96; 95% CI, 1.35-11.63; P=.01 for female HCPs).
Nurses were more likely than physicians and APPs to take time off (AOR, 3.33; 95%
CI, 1.10-10.09; P=.03.) CONCLUSIONS Presenteeism among HCPs with ILI is common,
including among those caring for transplant recipients. Nonpunitive systems
should encourage HCPs not to work with ILI and to wear masks to prevent spread of
infections. Infect Control Hosp Epidemiol 2017;38:966-969.
PMID- 28514977
TI - Cross-cultural adaptation and validation of the Newest Vital Sign (NVS) health
literacy instrument in general population and highly educated samples of
Brazilian adults.
AB - OBJECTIVE: The present work aimed at cross-cultural adaptation and validation of
the health literacy assessment tool Newest Vital Sign (NVS) in general population
(GP) and highly educated (HE) samples of Brazilian adults. DESIGN: An expert
committee reviewed the translation and back-translation processes and the
cultural adaptation. The construct validity was analysed with confirmatory factor
analysis and via associations with features of the study population. SETTING: The
final validation test was performed in two different populations from Londrina, a
large town in southern Brazil. SUBJECTS: Brazilian adults: GP (adult clients of
community pharmacies; n 189) and HE (public school teachers; n 301). RESULTS: The
tool under validation showed good cross-cultural adaptation and internal
consistency, with Cronbach's alpha of 0.75 for GP and 0.74 for HE. Confirmatory
factor analysis showed acceptable models and identified two independent factors
according to the relationship between components and numeracy for both GP and HE
data. According to the Brazilian Portuguese version of the NVS instrument (NVS
BR), 48.7 % of GP and 33.5 % of HE presented adequate health literacy; this
condition was inversely associated with age for both populations and directly
correlated with educational level for GP. CONCLUSIONS: The NVS-BR showed good
validity in two different populations of Brazilian adults and can be considered
an alternative in screening for inadequate health literacy.
PMID- 28514978
TI - Jugular-infused methionine, lysine and branched-chain amino acids does not
improve milk production in Holstein cows experiencing heat stress.
AB - Poor utilization of amino acids contributes to losses of milk protein yield in
dairy cows exposed to heat stress (HS). Our objective was to test the effect of
essential amino acids on milk production in lactating dairy cows exposed to short
term HS conditions. To achieve this objective, 12 multiparous, lactating Holstein
cows were assigned to two environments (thermoneutral (THN) or HS) from days 1 to
14 in a split-plot type cross-over design. All cows received 0 g/day of essential
amino acids from days 1 to 7 (negative control (NC)) followed by an intravenous
infusion of l-methionine (12 g/day), l-lysine (21 g/day), l-leucine (35 g/day), l
isoleucine (15 g/day) and l-valine (15 g/day, methionine, lysine and branched
chain amino acids (ML+BCAA)) from days 8 to 14. The basal diet was composed of
ryegrass silage and hay, and a concentrate mix. This diet supplied 44 g of
methionine, 125 g of lysine, 167 g of leucine, 98 g of isoleucine and 109 g of
valine per day to the small intestine of THN cows. Temperature-humidity index was
maintained below 66 for the THN environment, whereas the index was maintained
above 68, peaking at 76, for 14 continuous h/day for the HS environment. Heat
stress conditioning increased the udder temperature from 37.0 degrees C to 39.6
degrees C. Cows that received the ML+BCAA treatment had greater p.m. rectal and
vaginal temperatures (0.50 degrees C and 0.40 degrees C, respectively), and
respiration rate (8 breaths/min) compared with those on the NC treatment and
exposed to a HS environment. However, neither NC nor ML+BCAA affected rectal or
vaginal temperatures and respiration rates in the THN environment. Compared with
THN, the HS environment reduced dry matter intake (1.48 kg/day), milk yield (2.82
kg/day) and milk protein yield (0.11 kg/day). However, compared with NC, the
ML+BCAA treatment increased milk protein percent by 0.07 points. For the THN
environment, the ML+BCAA treatment increased concentrations of milk urea
nitrogen. For the HS environment, the ML+BCAA treatment decreased plasma
concentrations of arginine, ornithine and citrulline; however, differences were
not observed for the THN environment. In summary, HS elicited expected changes in
production; however, infusions of ML+BCAA failed to increase milk protein yield.
Lower dry matter intake and greater heat load in response to ML+BCAA contributed
to the lack of response in milk production in HS cows. The ML+BCAA treatment may
have reduced the breakdown of muscle protein in heat-stressed cows.
PMID- 28514979
TI - Determination of a Cutoff Time Point for Prophylactic Exchange of Central Venous
Catheters for Prevention of Central Venous Catheter-Related Bloodstream
Infections in Patients with Hematological Malignancies.
PMID- 28514980
TI - Evaluation of benzimidazole resistance status in Ascaridia galli.
AB - Susceptability of Ascaridia galli to benzimidazole (BZ) was investigated using
faecal egg count reduction test (FECRT), in ovo larval development test (LDT) and
genetic markers (mutations at codons 167, 198 and 200 of beta-tubulin gene). Six
flocks (F1-F6) of a commercial laying hen farm with different number of exposure
to BZ were recruited. The FECR was calculated by analyzing individual faeces (F1,
F2, F4 and F5) before and 10 days after treatment. The LDT was performed on
parasite eggs from pooled samples from F1 to F6 and LC50 and LC99 were
calculated. DNA was extracted from 120 worms and sequenced for beta-tubulin gene.
In all flocks, the FECRs were above 95% (lower CI above 90%). No significant
difference was observed (p > 0.05) among obtained LC50 (F1/F4 and F2/F5 vs F3/F6)
in the LDT. However, LC50 and LC99 were higher than suggested values for
declaration of resistance in other nematode species. No variation was observed in
codon positions involved in BZ resistance. Overall, our results indicated lack of
evidence of resistance to BZ in A. galli. More research is needed to confirm
these results and to further optimize the existing tools for detection and
monitoring of anthelmintic resistance in A. galli.
PMID- 28514981
TI - Essential Lessons in a Potential Sarin Attack Disaster Plan for a Resource
Constrained Environment.
AB - Sarin is a potent nerve agent chemical weapon that was originally designed for
military purposes as a fast-acting anti-personnel weapon that would kill or
disable large numbers of enemy troops. Its potent toxicity, ease of deployment,
and rapid degradation allow for rapid deployment by an attacking force, who can
safely enter the area of deployment a short while after its release. Sarin has
been produced and stockpiled by a number of countries, and large quantities of it
still exist despite collective agreements to cease manufacture and destroy
stockpiles. Sarin's ease of synthesis, which is easily disseminated across the
Internet, increases the risk that terrorist organizations may use sarin to attack
civilians. Sarin has been used in a number of terrorist attacks in Japan, and
more recently in attacks in the Middle East, where nonmilitary organizations have
led much of the disaster relief and provision of medical care. In the present
article, we examine and discuss the available literature on sarin's historical
use, delivery methods, chemical properties, mechanism of action, decontamination
process, and treatment. We present a management guideline to assist with the
recognition of an attack and management of victims by medical professionals and
disaster relief organizations, specifically in resource-constrained and austere
environments. (Disaster Med Public Health Preparedness. 2018;12:249-256).
PMID- 28514982
TI - EVALUATION CRITERIA OF PATIENT AND PUBLIC INVOLVEMENT IN RESOURCE ALLOCATION
DECISIONS: A LITERATURE REVIEW AND QUALITATIVE STUDY.
AB - OBJECTIVES: We developed specific evaluation criteria to assess patient and
public involvement in resource allocation decisions in health care. METHODS: We
reviewed the literature from health and other sectors relevant to stakeholder
involvement and conducted twenty-seven key informant interviews with stakeholders
knowledgeable about patient and public involvement in Canadian drug resource
allocation decisions. We used an inductive qualitative thematic approach to
analyze the interviews with codes and categories developed directly from
individuals' interview transcripts. RESULTS: Integrating respondents' comments
and the literature review, we identified nine evaluation criteria of patient and
the public involvement in healthcare resource allocation decision making: clarity
regarding rationale and roles of patient and public members, sufficient support,
adequate representation of relevant views, fair decision-making processes,
legitimacy of committee processes, adequate opportunity for participation,
meaningful degree of participation, noticeable effect on decisions, and
considerations of the efficiency of patient and public involvement. CONCLUSIONS:
Our results will help to develop methods to evaluate patient and public
involvement in healthcare decision making.
PMID- 28514983
TI - Adverse effects of consuming high fat-sugar diets on cognition: implications for
understanding obesity.
AB - There is increasing evidence for important roles of key cognitive processes,
including attention, memory and learning, in the short-term decision making about
eating. There is parallel evidence that people who are overweight or obese tend
to perform worse on a variety of cognitive tasks. In this review, the evidence
for these two ideas is summarised and then the idea that overconsumption of
Western-style high-fat (HF)-high-sugar diets may underlie the association between
obesity and poorer cognitive performance is explored. In particular, evidence in
animals and human subjects that repeated consumption of HF or HF and sugar (HFS)
diets leads to specific impairments in the functioning of the hippocampus, which
underpin the consequent changes in cognition is summarised. These findings lead
into the vicious cycle model (VCM), which suggests that these cognitive changes
have knock-on negative effects for future appetite control, and evidence that
altered hippocampal function is also associated with impaired appetite control is
explored. The review concludes that there is consistent evidence in the animal
literature and emerging evidence from human studies that supports this VCM. It is
also noted, however, that to date studies lack the nutritional specificity needed
to be able to translate these basic research findings into clear nutritional
effects, and concludes that there is an urgent need for additional research to
clarify the precise nature of the apparent effects of consuming HFS diets on
cognition.
PMID- 28514984
TI - Alternate Mediterranean diet score is positively associated with skeletal muscle
mass index in middle-aged adults.
AB - Researches have suggested Mediterranean diet might lower the risk of chronic
diseases, but data on skeletal muscle mass (SMM) are limited. This community
based cross-sectional study examined the association between the alternate
Mediterranean diet score (aMDS) and SMM in 2230 females and 1059 males aged 40-75
years in Guangzhou, China. General information and habitual dietary information
were assessed in face-to-face interviews conducted during 2008-2010 and 3 years
later. The aMDS was calculated by summing the dichotomous points for the items of
higher intakes of whole grain, vegetables, fruits, legumes, nuts, fish and ratio
of MUFA:SFA, lower red meat and moderate ethanol consumption. The SMM of the
whole body, limbs, arms and legs were measured using dual-energy X-ray
absorptiometry during 2011-2013. After adjusting for potential covariates, higher
aMDS was positively associated with skeletal muscle mass index (SMI, SMM/height2,
kg/m2) at all of the studied sites in males (all P trend<0.05). The multiple
covariate-adjusted SMI means were 2.70 % (whole body), 2.65 % (limbs), 2.50 %
(arms) and 2.70 % (legs) higher in the high (v. low) category aMDS in males (all
P<0.05). In females, the corresponding values were 1.35 % (P trend=0.03), 1.05,
0.52 and 1.20 %, (P trend>0.05). Age-stratified analyses showed that the
favourable associations tended to be more pronounced in the younger subjects aged
less than the medians of 59.2 and 62.2 years in females and males (P
interaction>0.10). In conclusion, the aMDS shows protective associations with SMM
in Chinese adults, particularly in male and younger subjects.
PMID- 28514985
TI - New technology in nutrition research and practice.
AB - Recent technology advancements are aiding the development of scientific
discoveries and changing the methods by which we perform research. In order to
gain full benefits for human health, it will be important to embrace these new
technologies in nutrition research while also acknowledging their limitations.
The present issue covers a range of technological approaches that impact on
public health nutrition and molecular nutrition. The critical appraisal of these
approaches in the context of nutrition research makes this issue a timely and
pertinent addition to the scientific literature.
PMID- 28514986
TI - Lorenz Oken (1779-1851): Naturphilosophie and the reform of natural history.
AB - The paper focuses on the work of Lorenz Oken (1779-1851) in an attempt to make
sense of the role played by Romantic Naturphilosophie in the development of
natural history in Germany at the turn of the nineteenth century. It first
focuses on the role played by Schelling and his Wurzburg circle in the
development of Oken's early views on natural history, then reconstructs Oken's
mature programme for a reform of animal classification.
PMID- 28514987
TI - A systematic review of the prevalence and predictors of the double burden of
malnutrition within households.
AB - Recently, increasing attention has been paid to the emergence of the double
burden of malnutrition within households. We provide an overview of the
literature regarding this phenomenon by reviewing previous studies of the
prevalence of double-burden households and associated factors together with the
research methods used. Studies were identified from the electronic databases
PubMed and Web of Science, using the same search terms for both. A total of
thirty-five articles met the eligibility criteria, and 367 sets of prevalence
data were extracted. In all, thirty-four articles were published in 2000 or
later; twenty-four used secondary data and twenty-five focused on mother-child
pairs. The ages of children varied from 0 to 19 years. All the studies used BMI
as a nutritional indicator for adults. For children, height-for-age was most
frequently used, whereas weight-for-age, weight-for-height and BMI-for-age were
also used in multiple studies. The reported national prevalence of double-burden
households varied from 0.0 to 26.8 % by country and year; however, few studies
were directly comparable, because of differences in the combinations of
undernourished and overweight persons, age ranges, nutritional indicators and cut
off points. Whereas many focused on African countries, a few involved Asian
countries. Although urban residence, income and education were frequently
assessed, the role of intermediate factors in nutritional status, such as diet
and physical activity, remains unclear. It is recommended that future studies use
comparable indicators and cut-off points, involve Asian countries, and
investigate individual diet and physical activity.
PMID- 28514988
TI - How Latina mothers navigate a 'food swamp' to feed their children: a photovoice
approach.
AB - OBJECTIVE: To understand how mothers who recently migrated from Central America
to the USA feed their children in a neighbourhood saturated with unhealthful food
choices ('food swamp') and to formulate a mother-driven plan of action to
facilitate their acquisition of foods. Design/Setting/Subjects We purposively
sampled mothers with children (<10 years old) who were recent immigrants/refugees
from Central America and lived in a 'food swamp' neighbourhood. We used the
photovoice approach to elicit textual data from thirty in-depth interviews, a
participatory workshop, and visual data from photographs. Analyses were guided by
the Social Ecological Framework and Social Cognitive Theory to identify barriers,
facilitators and strategies that support parents in feeding their children.
RESULTS: Mothers valued foods that they considered to be 'traditional' and
'healthful'. They navigated their food retail environment looking for these foods
(of good quality and well-priced). Food values were reinforced by pre-migration
food customs and culture, health professionals' advice and, in some cases, by the
desire to avoid conflict with their children. The neighbourhood food environment
could directly influence children's food preferences and often created conflict
between what the child wanted to eat and the foods that mothers valued. Mothers
in this 'food swamp' wanted to be engaged in addressing the selection of foods
offered in schools and in neighbourhood food venues to reflect their own food
values. CONCLUSIONS: These mothers' feeding choices were influenced directly by
their food values, and indirectly by the neighbourhood and school food
environments via their children's preferences.
PMID- 28514989
TI - Help-seeking intentions for anxiety among older adults.
AB - Mental health practices are not working for older people with anxiety in
residential care, as there is a persistent lack of recognition and treatment.
This suggests that alternative ways of reaching and meeting the needs of this
population need to be explored. One possibility involves enabling older adults
themselves to seek help. The current work explored various factors impacting on
help-seeking behaviours. In total, 105 participants from independent living units
in a residential care setting completed a questionnaire focusing on attitudes and
stigma towards anxiety, likelihood to seek help, help-seeking barriers and
literacy around the symptoms of anxiety. Participants in the main did not hold
negative attitudes towards other people with anxiety, despite concerns that other
people could view them negatively if they were experiencing anxiety. Barriers to
help-seeking included: difficulties recognising physical anxiety symptoms as
being indicative of anxiety; the effectiveness of treatments; costs;
misdiagnosis; privacy; medication usage and the associated side-effects; and,
uneasiness about the skills and knowledge of health professionals. Although
concerns were not held by all participants, the fact remains that anxiety is
largely undiagnosed and untreated for this population and these stoppages to
appropriate care must be addressed.
PMID- 28514990
TI - Prevalence of porA pseudogene deletion among Neisseria gonorrhoeae isolates
referred to the UK's Gonococcal Resistance to Antimicrobials Surveillance
Program.
AB - porA pseudogene-negative Neisseria gonorrhoeae isolates produce false-negative
results when examined by polymerase chain reaction (PCR) with porA pseudogene
targets. In the present study, 533 representative gonococcal isolates received in
2011 via the Gonococcal Resistance to Antimicrobials Surveillance Program were
examined to determine the prevalence of porA-negative isolates. Less than 0.4%
(2/533) of isolates were found to be reproducibly negative with the porA real
time PCR but were confirmed as N. gonorrhoeae with molecular, biochemical and
immunological confirmatory tests. Sequencing revealed both isolates contained the
Neisseria meningitidis porA gene. Low prevalence indicates that although these
isolates do not present a major public health problem, microbiologists should
remain vigilant.
PMID- 28514991
TI - Pregnant young women's attitudes about microbicides: the anticipated influence of
the grandmother and father of the baby on microbicide use.
AB - Grandmothers and fathers of the baby may influence pregnant women's microbicide
use. Pregnant young women's attitudes about grandmothers' and fathers' role in
decision-making and their involvement in microbicide use were assessed.
Participants (n=108) had a mean age of 20.2 years. The majority anticipated that
the grandmother, father or both would have a decision-making role. Greater
grandmother involvement in microbicide use was significantly associated with
being younger, having no reproductive tract infection or contraceptive-ring-use
history. Greater father involvement in use was associated with being in a
relationship with him. Strategies for engaging grandmothers and fathers in
microbicide use should be developed.
PMID- 28514992
TI - Sexual difficulties faced by men in the Solomon Islands: a mixed-methods study.
AB - : Background To date there has been little research into men's sexual and
reproductive health in Pacific Island countries. The aim of this study was to
describe men's sexual difficulties and barriers to their seeking reproductive
health care in the Solomon Islands. METHODS: The study included qualitative
inquiry (17 individual interviews and three focus group discussions with a total
of 21 men) and a quantitative quasi-randomised quota sample household survey
(n=400). The prevalence of sexual difficulties and potential risk factors, such
as chronic diseases, health risk behaviours, depression and psychological
distress were measured using standardised questions translated into pidgin.
RESULTS: The most commonly self-reported sexual difficulties were premature
ejaculation (39.5%), low sexual desire (29.0%), orgasm difficulty (27.3%) and
erectile difficulty (4.3%). More than half (56%) of the men experienced at least
one sexual difficulty. Relatively few men (7.3%) had ever sought professional
health care for reproductive health problems, and 15.4% of men preferred to use
kastom (traditional) medicine for sexual problems. Multivariate analysis revealed
that comorbid non-communicable diseases (NCDs), low health-related quality of
life and dissatisfaction with sexual relationships were independently correlated
with sexual difficulties. Contrary to expectations, self-reported psychological
distress was inversely associated with these difficulties. In general, the
insights gained from in-depth interviews validated the survey findings.
CONCLUSION: This study adds the first data on symptoms of sexual dysfunction
among men in the Solomon Islands and is one of few studies from the Pacific
region. The findings strongly suggest the need for comprehensive health services
that are gender-specific and sensitive to the sexual difficulties of Islander
men.
PMID- 28514993
TI - Beyond diagnosis and survivorship: findings from a mixed-methods study of a
community-based cancer support service.
AB - This consumer-led research investigated the client experiences and the individual
and community benefits of a community-based cancer support service operating in a
regional setting. The study included cross-sectional surveys, focus group
discussions and key-informant interviews. In total, 114 clients, 28 carers and 20
therapists were surveyed; three client focus groups were conducted and five
directors and staff were interviewed. For many clients and carers, the warm
welcome experienced at first contact sets the tone for a long-term association
with the organisation. The feeling of being cared for extends to the broader
community and living with cancer becomes more than survivorship. Integral to the
organisational model are opportunity (second-hand) shops that enable subsidised
complementary therapies and other services, offer a way of giving back and assist
disadvantaged community members. The organisational model has benefits, not only
for people living with cancer and their families, but also for the wider
community.
PMID- 28514994
TI - Active syphilis and its association with HIV and sexual risk behaviours in a
multicity sample of men who have sex with men and transgender women in Peru.
AB - : Background Syphilis in Peru is heavily concentrated in men who have sex with
men (MSM) and transgender women (TGW). The aim of the present study was to
understand the risk factors for active syphilis infection among MSM and TGW in
Peru. METHODS: Independent correlates suggestive of active syphilis infection
were examined to better understand risk factors for syphilis in MSM and TGW, with
separate analyses conducted based on location and among TGW. In 2011, 5101 MSM
and TGW completed both self-report surveys and HIV and syphilis testing in five
Peruvian cities. RESULTS: Overall, 261 (5.1%) MSM and TGW met the criteria for
active syphilis, with higher prevalence in Lima than elsewhere (7.0% vs 3.0%) and
in TGW than in MSM (10.7% vs 4.2%). Significant independent correlates of active
syphilis infection differed greatly by location. In Lima, they included being HIV
infected (aware or unaware of status), being a TGW, being a high school graduate,
engaging in receptive anal intercourse, no recent sex with a female partner and
having had any symptomatic sexually transmissible infection, including syphilis,
in the previous 6 months. Outside Lima, the independent correlates included being
HIV-infected and unaware of status, engaging in recent sex work, no recent sex
with a female partner and age 35-44 years. Among TGW, independent correlates of
active syphilis included being HIV-infected (aware or unaware of status), a
recent syphilis diagnosis in the previous 6 months and recent drug use.
CONCLUSION: The findings of the present study support the need not only for
combined HIV and syphilis screening, but also for increased screening and
treatment of syphilis in MSM and TGW populations. Stratified analyses suggest
different syphilis epidemics throughout the country and in TGW, yet being HIV
infected and aware were consistently associated with active syphilis, suggesting
higher syphilis risk in HIV-infected MSM and TGW.
PMID- 28514995
TI - Tobacco smoking and sexual difficulties among Australian adults: a cross
sectional study.
AB - : Background Few studies have examined smoking and female sexual difficulties.
The aim of this study was to investigate the association between current tobacco
smoking and sexual difficulties in Australian men and women. METHODS: Data for
this study came from the Second Australian Study of Health and Relationships
(2012-13), which includes a representative sample of 18427 sexually active
Australian adults (aged 16-69 years). The main study and outcome measures were
tobacco smoking and sexual difficulties. A multiple logistic regression analysis
was conducted to adjust for potential confounders. RESULTS: Male heavy smokers
(>20 cigarettes per day) were significantly more likely than non-smokers to have
trouble keeping an erection [adjusted odds ratio (AOR) 4.14, 95% confidence
interval (CI) 1.87-9.20; P<0.0001], lack interest in having sex (AOR 2.18, 95% CI
1.20-3.97; P=0.011), have anxiety about performance (AOR 2.46, 95% CI 1.24-4.86;
P=0.010) and be unable to come to orgasm (AOR=2.81, 95% CI 1.23-6.42; P=0.015).
Female smokers were also significantly more likely than non-smokers to not find
sex pleasurable (AOR 1.48, 95% CI 1.05-2.07; P=0.025); and light female smokers
were significantly more likely than non-smokers to be unable to come to orgasm
(AOR=1.44, 95% CI 1.05-1.98; P=0.025). CONCLUSIONS: Current tobacco smoking was
associated with sexual difficulties in both men and women. For women, even light
smoking was associated with not finding sex pleasurable and being unable to come
to orgasm.
PMID- 28514996
TI - Post-autopsy computed tomography. Pros and cons in a firearm death.
AB - Many studies have focused on the importance of post-mortem computed tomography
(PMCT) prior to or in substitution of standard forensic autopsies in case of
firearm death. However, due to the fact that PMCT is not routinely performed in
all countries, in cases of death abroad it can happen that a CT scan is performed
only after a first autopsy. A case of post-mortem re-examination, including the
external examination and a post-autopsy computed tomography (PACT), of a gunshot
victim of homicide in a foreign country is presented, and the pros and cons of
imaging in post-autopsy setting are discussed. PACT could be a tool for carrying
out more complete investigations and for obtaining information on bone injuries
and foreign bodies trapped within peripheral soft tissues that can be re-analyzed
after the arrival of the first autopsy report. Given that the value of
information derived may be strongly influenced by the previously performed
autopsy, in order to process the definitive considerations it is necessary to
compare and interpret the data obtained through PACT with the results of the
first autopsy, and to continue the international cooperation effort and the
application of international guidelines in order to share information at the
repatriation of the corpse.
PMID- 28514997
TI - The prevalence of food allergy and other allergic diseases in early childhood in
a population-based study: HealthNuts age 4-year follow-up.
AB - BACKGROUND: The HealthNuts study previously reported interim prevalence data
showing the highest prevalence of challenge-confirmed food allergy in infants
internationally. However, population-derived prevalence data on challenge
confirmed food allergy and other allergic diseases in preschool-aged children
remain sparse. OBJECTIVE: This study aimed to report the updated prevalence of
food allergy at age 1 year from the whole cohort, and to report the prevalence of
food allergy, asthma, eczema, and allergic rhinitis at age 4 years. METHODS:
HealthNuts is a population-based cohort study with baseline recruitment of 5276
one-year-old children who underwent skin prick test (SPT) to 4 food allergens and
those with detectable SPT results had formal food challenges. At age 4 years,
parents completed a questionnaire (81.3% completed) and those who previously
attended the HealthNuts clinic at age 1 year or reported symptoms of a new food
allergy were invited for an assessment that included SPT and oral food
challenges. Data on asthma, eczema, and allergic rhinitis were captured by
validated International Study of Asthma and Allergies in Childhood
questionnaires. RESULTS: The prevalence of challenge-confirmed food allergy at
age 1 and 4 years was 11.0% and 3.8%, respectively. At age 4 years, peanut
allergy prevalence was 1.9% (95% CI, 1.6% to 2.3%), egg allergy was 1.2% (95% CI,
0.9% to 1.6%), and sesame allergy was 0.4% (95% CI, 0.3% to 0.6%). Late-onset
peanut allergy at age 4 years was rare (0.2%). The prevalence of current asthma
was 10.8% (95% CI, 9.7% to 12.1%), current eczema was 16.0% (95% CI, 14.7% to
17.4%), and current allergic rhinitis was 8.3% (95% CI, 7.2% to 9.4%). Forty
percent to 50% of this population-based cohort experienced symptoms of an
allergic disease in the first 4 years of their life. CONCLUSIONS: Although the
prevalence of food allergy decreased between age 1 year and age 4 years in this
population-based cohort, the prevalence of any allergic disease among 4-year-old
children in Melbourne, Australia, is remarkably high.
PMID- 28514998
TI - Affibody Molecules in Biotechnological and Medical Applications.
AB - Affibody molecules are small (6.5-kDa) affinity proteins based on a three-helix
bundle domain framework. Since their introduction 20 years ago as an alternative
to antibodies for biotechnological applications, the first therapeutic affibody
molecules have now entered clinical development and more than 400 studies have
been published in which affibody molecules have been developed and used in a
variety of contexts. In this review, we focus primarily on efforts over the past
5 years to explore the potential of affibody molecules for medical applications
in oncology, neurodegenerative, and inflammation disorders, including molecular
imaging, receptor signal blocking, and delivery of toxic payloads. In addition,
we describe recent examples of biotechnological applications, in which affibody
molecules have been exploited as modular affinity fusion partners.
PMID- 28514999
TI - Severe hypovitaminosis D in active tuberculosis patients and its predictors.
AB - BACKGROUND & AIMS: Tuberculosis (TB) patients have a significant vitamin D
deficiency (VDD) endemic, which may be closely related to the onset and progress
of the disease. The comorbidity of diabetes (DM) and TB has posed an increasing
challenge in recent years. However, the influence of DM on TB and the possible
mechanism are still uncertain. We carried out this study to identify the
nutritional status of vitamin D (VD) in TB patients in a northern city in China
(latitude 36 degrees N) and investigate the possible predictors of severe
vitamin D deficiency (SVDD). METHODS: A cross-sectional study including 461
active TB patients (192 with and 269 without DM) were randomly selected from
Qingdao Chest Hospital from June 2015 to August 2016. We measured serum 25
hydroxyvitamin D [25(OH)D], and investigated the association between
sociodemographic, dietary intake, DM, body mass index (BMI), severity of initial
TB signs and symptoms (TB score) and VD status. Multivariate logistic regression
analysis was used to define the possible predictors of SVDD. RESULTS: The median
serum 25(OH)D concentration was 8.50 ng/mL. Of the 461 TB patients included, 383
(83.1%) had VDD [25(OH)D < 20 ng/mL], and 217 (47.1%) had SVDD [25(OH)D < 8
ng/mL]. The variables associated with serum 25(OH)D concentrations were DM,
outdoor activity level, TB score and BMI (p < 0.05). Patients with severe TB
score had nearly 5 fold higher risk of having SVDD compared with those in mild
subgroup [OR (95% CI) = 4.919 (2.644-9.150), p < 0.001]. Low outdoor activity
level also increased the odds of SVDD, while DM and high fish consumption showed
protect effects. CONCLUSIONS: Severe hypovitaminosis D is prevalent in active TB
patients, and the main predictors of SVDD were severe TB score, low outdoor
activity, inadequate fish consumption. Lowered serum 25(OH)D may be associated
with increased risk of TB in DM.
PMID- 28515000
TI - Mitochondrial and endoplasmic reticulum calcium homeostasis and cell death.
AB - The endoplasmic reticulum (ER) and mitochondria cannot be considered as static
structures, as they intimately communicate, forming very dynamic platforms termed
mitochondria-associated membranes (MAMs). In particular, the ER transmits proper
Ca2+ signals to mitochondria, which decode them into specific inputs to regulate
essential functions, including metabolism, energy production and apoptosis. Here,
we will describe the different molecular players involved in the transfer of Ca2+
ions from the ER lumen to the mitochondrial matrix and how modifications in both
ER-mitochondria contact sites and Ca2+ signaling can alter the cell death
execution program.
PMID- 28515001
TI - In vitro extracellular matrix accumulation of nasal and articular chondrocytes
for intervertebral disc repair.
AB - Chondrocyte based regenerative therapies for intervertebral disc repair such as
Autologous Disc Cell Transplantation (ADCT, CODON) and allogeneic juvenile
chondrocyte implantation (NuQu(r), ISTO Technologies) have demonstrated good
outcomes in clinical trials. However concerns remain with the supply demand
reconciliation and issues surrounding immunoreactivity which exist for allogeneic
type technologies. The use of stem cells is challenging due to high growth factor
requirements, regulatory barriers and differentiation towards a stable phenotype.
Therefore, there is a need to identify alternative non-disc cell sources for the
development and clinical translation of next generation therapies for IVD
regeneration. In this study, we compared Nasal Chondrocytes (NC) as a non-disc
alternative chondrocyte source with Articular Chondrocytes (AC) in terms of cell
yield, morphology, proliferation kinetics and ability to produce key
extracellular matrix components under 5% and 20% oxygen conditions, with and
without exogenous TGF-beta supplementation. Results indicated that NC maintained
proliferative capacity with high amounts of sGAG and lower collagen accumulation
in the absence of TGF-beta supplementation under 5% oxygen conditions.
Importantly, osteogenesis and calcification was inhibited for NC when cultured in
IVD-like microenvironmental conditions. The present study provides a rationale
for the exploration of nasal chondrocytes as a promising, potent and clinically
feasible autologous cell source for putative IVD repair strategies.
PMID- 28515002
TI - Electrocardiographic QRS-T angle and the risk of incident silent myocardial
infarction in the Atherosclerosis Risk in Communities study.
AB - BACKGROUND: Silent myocardial infarction (SMI) accounts for about half of the
total number of MIs, and is associated with poor prognosis as is clinically
documented MI (CMI). The electrocardiographic (ECG) spatial QRS/T angle has been
a strong predictor of cardiovascular outcomes. Whether spatial QRS/T angle also
is predictive of SMI, and the easy-to-obtain frontal QRS/T angle will show
similar association are currently unknown. METHODS: We examined the association
between the spatial and frontal QRS/T angles, separately, with incident SMI among
9498 participants (mean age 54years, 57% women, and 20% African-American), who
were free of cardiovascular disease at baseline (visit 1, 1987-1989) from the
Atherosclerosis Risk in Communities (ARIC) study. Incident SMI was defined as MI
occurring after the baseline until visit 4 (1996-1998) without CMI. The frontal
plane QRS/T angle was defined as the absolute difference between QRS axis and T
axis. Values greater than the sex-specific 95th percentiles of the QRS/T angles
were considered wide (abnormal). RESULTS: A total of 317 (3.3%) incident SMIs
occurred during a 9-year median follow-up. In a model adjusted for demographics,
cardiovascular risk factors and potential confounders, both abnormal frontal (HR
2.28, 95% CI 1.58-3.29) and spatial (HR 2.10, 95% CI 1.44-3.06) QRS/T angles were
associated with an over 2-fold increased risk of incident SMI. Similar patterns
of associations were observed when the results were stratified by sex.
CONCLUSIONS: Both frontal and spatial QRS/T angles are predicative of SMI
suggesting a potential use for these markers in identifying individuals at risk.
PMID- 28515003
TI - Reverse atrial electrical remodeling induced by cardiac resynchronization
therapy.
AB - PURPOSE: Cardiac resynchronization therapy (CRT) has been shown to improve left
atrial function; however the effect on reverse electrical remodeling has been
poorly evaluated. We hypothesized that CRT might induce reverse atrial electrical
remodeling manifesting in the surface ECG as a shortening in P-wave duration.
METHODS: Patients with CRT and more than 92% biventricular pacing at minimum
follow-up of 1 year were included in the analysis. Those with prior history of
atrial fibrillation (AF) were excluded. Data were recorded for clinical,
echocardiographic and ECG variables prior to implant and at least 12 months post
implantation. Semiautomatic calipers and scanned ECGs at 300 DPI maximized * 8
were used to measure P-wave duration and diagnose advanced interatrial block
(aIAB) during sinus rhythm. The occurrence of AF was assessed through analyses of
intracardiac electrograms and clinical presentations. RESULTS: 41 patients were
included in the study with mean age of 67.4 +/-9.6 years, 71% were male, left
atrial diameter 41.1 +/- 8.5 mm and LV EF 28.5 +/- 6.5%. Over a mean follow up of
55 months, a significant reduction in P-wave duration (142.7 ms vs. 133.1 ms; p <
0.001) was noted. The presence of aIAB was significantly reduced (36% vs. 17%; p
= 0.03). The incidence of new onset AF was 36%. Time to AF onset after CRT
implantation was not influenced by a reduction in P-wave duration. CONCLUSION:
CRT induces atrial reverse electrical remodeling manifested as a reduction in P
wave duration. Larger studies are needed to determine the impact on AF incidence
after CRT implantation.
PMID- 28515004
TI - Animal breeding strategies can improve meat quality attributes within entire
populations.
AB - The contribution of animal breeding to changes in animal performance is well
documented across a range of species. Once genetic variation in a trait exists,
then breeding to improve the characteristics of that trait is possible, if so
desired. Considerable genetic variation exists in a range of meat quality
attributes across a range of species. The genetic variation that exists for meat
quality is as large as observed for most performance traits; thus, within a well
structured breeding program, rapid genetic gain for meat quality could be
possible. The rate of genetic gain can be augmented through the integration of
DNA-based technologies into the breeding program; such DNA-based technologies
should, however, be based on thousands of DNA markers dispersed across the entire
genome. Genetic and genomic technologies can also have beneficial impact outside
the farm gate as a tool to segregate carcasses or meat cuts based on expected
meat quality features.
PMID- 28515005
TI - Dynamics of a True Moving Bed separation process: Linear model identification and
advanced process control.
AB - The control of Simulated Moving Bed (SMB) units is challenging due to their
complex dynamic behaviour and the difficulty of measuring their main properties.
Furthermore, for the SMB units, the transfer function identification when the
unit is operating at its optimal point is not easy to be done through the usual
way. This work presents the development of a novel strategy to identify transfer
functions of TMB/SMB and its application on classical linear model predictive
controllers (MPC). However, for the process in study, due its unique dynamics,
only the identification of the linear model is not enough to solve its control
problem. Therefore, it is proposed a modification in the MPC prediction, that
consists in a strategy based on a switching system where the most adequate
transfer function is employed in the controller to overcome the problems related
with the process dynamic behaviour. The results show that the used methodology
enables the easy identification of transfer functions at the process optimal
operating point and that the MPC can control the process in both the servo and
regulator problem cases. It is also showed that the transfer function identified
can be applied in the control of a SMB unit with four columns, under its optimal
conditions.
PMID- 28515006
TI - Two-dimensional multi-heart cutting centrifugal partition chromatography-liquid
chromatography for the preparative isolation of antioxidants from Edelweiss
plant.
AB - The Edelweiss plant has been recognized as a very valuable source of anti-aging
principles due to its composition of antioxidants compounds: leontopodic acid A
and 3,5-dicaffeoylquinic acid. In this work, off-line multi-heart cutting CPC-LC
separation was set up at industrial scale in order to isolate and produce new
high quality reference material of these two antioxidants from Edelweiss. For
this purpose, CPC and HPLC methods were developed and optimized at laboratory
scale and a comprehensive CPCxHPLC analysis of the crude extract was established.
Thereby, the CPC method led to a first separation of the target compounds
according to their partition coefficient in the solvent system and the HPLC
method was performed on the recovered fractions to lead to a second separation. A
2D CPCxHPLC plot was established in order to know the fractions to select at the
industrial scale. Then, the CPC and HPLC methods were transferred at industrial
scale and the multi-heart cutting CPC-LC was performed in off-line mode. Using
CPC with methyl ter-butyl ether-water 1:1 (v/v) solvent system and LC with Denali
C18 column, 2g of crude extract sample were injected and leontopodic acid A and
3,5-dicaffeoylquinic acid were recovered with purity over 97%. The compounds were
identified by MS and NMR.
PMID- 28515007
TI - Effects of maternal traumatic distress on family functioning and child mental
health: An examination of Southeast Asian refugee families in the U.S.
AB - BACKGROUND: The psychological effects of trauma are well-documented among refugee
adults and children alone, yet less research has attended to the
intergenerational transmission of trauma within refugee families. Additionally,
there is considerable diversity between refugee populations as well as within
group variation in the experiences and effects of refugee trauma. OBJECTIVE: The
current study examines the longitudinal effects of maternal traumatic distress on
family functioning and child mental health outcomes among Southeast Asian refugee
women and their adolescent children. Given the potential for variation in these
effects, we also explore group differences in these relationships by ethnicity
and child nativity. METHODS: Longitudinal data were collected from a random
sample of 327 Southeast Asian refugee mothers and their children in the United
States. We employed structural equation modeling to examine associations between
latent variables representing maternal traumatic distress, family functioning,
and child mental health outcomes (i.e., depressive symptoms, antisocial and
delinquent behavior, and school problems). We then tested for group differences
in these associations by ethnicity (Cambodian and Vietnamese subgroups) and child
nativity (U.S.-born and foreign-born children). RESULTS: We found maternal
traumatic distress was indirectly linked to child mental health outcomes, and
that child nativity was associated with these paths while ethnicity was not. For
foreign-born children, maternal traumatic distress was associated with diminished
family functioning a year later, which was associated with increased school
problems at the two-year mark. Maternal traumatic distress was indirectly
associated with depressive symptoms and antisocial and delinquent behavior,
respectively, after accounting for family functioning. For all children, weaker
family functioning was significantly associated with poorer mental health.
CONCLUSIONS: Findings suggest that refugee parents' trauma can adversely affect
family relationships and the mental health of children. Interventions that
address parental trauma and support intergenerational relationships may enhance
mental health within refugee communities for future generations.
PMID- 28515008
TI - Localization and distribution of gonadal proteins in the oviparous lizard
Sceloporus aeneus (Squamata: Phrynosomatidae).
AB - Among vertebrates, several specific proteins are involved in the function and
development of gonads. Several genes such as SOX9, FOXL2, DDX4, IFITM3, and
DPPA3, are active during embryonic differentiation and maintain their expression
in adult tissues, playing important roles in the function and development of the
line cell, where these are produced. Among reptiles, molecular mechanisms for sex
differentiation have been analyzed in turtles, crocodiles, and some lizards,
while in adult stages such studies are scarce. The aim of this study was to
locate and analyze the distribution of important gonadal proteins in adult and
embryonic ovaries and testes of the oviparous lizard Sceloporus aeneus (Squamata:
Phrynosomatidae). Adult specimens and embryos of the lizard S. aeneus were
collected in Milpa Alta, a suburb located Southwest of Mexico City. Expression of
gonadal proteins was analyzed using immunofluorescent staining and confocal
microscopy. Our results showed that SOX9 is located in Sertoli cells of embryonic
and adult testes. FOXL2 is expressed in follicular cells of adult ovaries. DDX4
and IFITM3 are located in germ line cells as well as in follicular cells of adult
ovaries. DPPA3 was observed in somatic and germ line cells of adult and embryonic
gonads. Our observations show that important molecules of vertebrate ovaries and
testes are conserved in S. aeneus and it is suggested that these may have a
similar role during gonadal development and function.
PMID- 28515009
TI - Transfer learning on fused multiparametric MR images for classifying
histopathological subtypes of rhabdomyosarcoma.
AB - This paper presents a deep-learning-based CADx for the differential diagnosis of
embryonal (ERMS) and alveolar (ARMS) subtypes of rhabdomysarcoma (RMS) solely by
analyzing multiparametric MR images. We formulated an automated pipeline that
creates a comprehensive representation of tumor by performing a fusion of
diffusion-weighted MR scans (DWI) and gadolinium chelate-enhanced T1-weighted MR
scans (MRI). Finally, we adapted transfer learning approach where a pre-trained
deep convolutional neural network has been fine-tuned based on the fused images
for performing classification of the two RMS subtypes. We achieved 85% cross
validation prediction accuracy from the fine-tuned deep CNN model. Our system can
be exploited to provide a fast, efficient and reproducible diagnosis of RMS
subtypes with less human interaction. The framework offers an efficient
integration between advanced image processing methods and cutting-edge deep
learning techniques which can be extended to deal with other clinical domains
that involve multimodal imaging for disease diagnosis.
PMID- 28515011
TI - Sustained Activity Encoding Working Memories: Not Fully Distributed.
AB - Working memory (WM) is the ability to remember and manipulate information for
short time intervals. Recent studies have proposed that sustained firing encoding
the contents of WM is ubiquitous across cortical neurons. We review here the
collective evidence supporting this claim. A variety of studies report that
neurons in prefrontal, parietal, and inferotemporal association cortices show
robust sustained activity encoding the location and features of memoranda during
WM tasks. However, reports of WM-related sustained activity in early sensory
areas are rare, and typically lack stimulus specificity. We propose that robust
sustained activity that can support WM coding arises as a property of association
cortices downstream from the early stages of sensory processing.
PMID- 28515010
TI - Aberrant Network Activity in Schizophrenia.
AB - Brain dynamic changes associated with schizophrenia are largely equivocal, with
interpretation complicated by many factors, such as the presence of therapeutic
agents and the complex nature of the syndrome itself. Evidence for a brain-wide
change in individual network oscillations, shared by all patients, is largely
equivocal, but stronger for lower (delta) than for higher (gamma) bands. However,
region-specific changes in rhythms across multiple, interdependent, nested
frequencies may correlate better with pathology. Changes in synaptic excitation
and inhibition in schizophrenia disrupt delta rhythm-mediated cortico-cortical
communication, while enhancing thalamocortical communication in this frequency
band. The contrasting relationships between delta and higher frequencies in
thalamus and cortex generate frequency mismatches in inter-regional connectivity,
leading to a disruption in temporal communication between higher-order brain
regions associated with mental time travel.
PMID- 28515012
TI - Breast cancer and exercise: The role of adiposity and immune markers.
AB - Currently, breast cancer accounts for a quarter of all cancers and 15% of cancer
specific deaths amongst females. The global occurrence of breast cancer has
increased in the last decade whilst the mortality rate has decreased. Exercise
can be beneficial to breast cancer patients through changes in adiposity and
immune responses. Even though there is some evidence supporting the improvement
of fat metabolism and immune function after an exercise program in breast cancer,
randomized controlled studies are limited and require further comprehensive
analysis in this population group. Herein, we identify the known effects of
exercise programs on adiposity and immunological markers which can improve breast
cancer outcomes.
PMID- 28515013
TI - Atomic force microscopy: From red blood cells to immunohaematology.
AB - Atomic force microscopy (AFM) offers complementary imaging modes that can provide
morphological and structural details of red blood cells (RBCs), and characterize
interactions between specific biomolecules and RBC surface antigen. This review
describes the applications of AFM in determining RBC health by the observation of
cell morphology, elasticity and surface roughness. Measurement of interaction
forces between plasma proteins and antibodies against RBC surface antigen using
the AFM also brought new information to the immunohaematology field. With
constant improvisation of the AFM in resolution and imaging time, the reaction of
RBC to changes in the physico-chemistry of its environment and the presence of
RBC surface antigen specific-biomolecules is achievable.
PMID- 28515015
TI - Collateral damage and the criminalisation of drug use.
PMID- 28515016
TI - Determination of the absolute configuration of a novel tetrasubstituted
isoindolinone by vibrational circular dichroism.
AB - The absolute configuration of a recently prepared asymmetric 3,3-disubstituted
isoindolinone (ethyl 2-benzyl-3-oxo-1-(3-oxobutyl)isoindoline-1-carboxylate),
possessing highly promising pharmaceutical activity, has been determined by means
of VCD spectroscopy and DFT calculations. The great flexibility of the molecule
reduces to a few relevant conformers, all contributing in the same way to the
shape of the VCD spectrum for the carbonyl stretching region. Two of the three CO
groups of the molecule interact with each other during the stretching vibration,
thus providing a non-conservative VCD couplet whose signature, together with the
VCD sign of the third CO stretching mode, unequivocally determines the absolute
configuration of the molecule, which is found to be (S) for the (-) optical
isomer.
PMID- 28515017
TI - Fatty acid-binding protein3 expression in BeWo cells, a human placental
choriocarcinoma cell line.
AB - Cellular uptake of long chain fatty acids in human placental trophoblasts is
thought to be mediated by several membrane- and cytoplasmic fatty acid-binding
proteins (FABP). FABP3 was shown to be involved in long chain polyunsaturated
fatty acids (LCPUFA) uptake in human trophoblastic choriocarcinoma cells, BeWo as
the uptake of arachidonic acid,20:4n-6 (ARA) was decreased in FABP3-knockdown
BeWo cells. However, the regulation of expression of FABP3 in these cells is not
yet well known. The aim of the present study was to examine the FABP3 expression
by LCPUFAs, insulin and LXR agonists in BeWo cells. Among all these fatty acids
tested, only ARA dose-dependently stimulated the expression of FABP3 protein in
these cells after 24h incubation while other fatty acids had no such effect. In
addition, LXR agonist and insulin dose-dependently increased FABP3 protein
expression in these cells after 24h incubation. Insulin-stimulated FABP3 protein
expression was accompanied with an increased arachidonic acid uptake.
Differentiated BeWo cells had lesser expression of FABP3 protein than in the
undifferentiated cells as the cellular differentiation state was measured by hCG
production. In preeclamptic placental tissue, lowered expression of FABP3 protein
was observed compared with those in normal pregnancy. All these data indicate
that FABP3 may in be part involved in ARA uptake in these cells and its
expression may be regulated by ARA, insulin, LXR and the state of cellular
differentiation.
PMID- 28515014
TI - HIV and the criminalisation of drug use among people who inject drugs: a
systematic review.
AB - BACKGROUND: Mounting evidence suggests that laws and policies prohibiting illegal
drug use could have a central role in shaping health outcomes among people who
inject drugs (PWID). To date, no systematic review has characterised the
influence of laws and legal frameworks prohibiting drug use on HIV prevention and
treatment. METHODS: Consistent with PRISMA guidelines, we did a systematic review
of peer-reviewed scientific evidence describing the association between
criminalisation of drug use and HIV prevention and treatment-related outcomes
among PWID. We searched MEDLINE, Embase, SCOPUS, PsycINFO, Sociological
Abstracts, CINAHL, Web of Science, and other sources. To be included in our
review, a study had to meet the following eligibility criteria: be published in a
peer-reviewed journal or presented as a peer-reviewed abstract at a scientific
conference; examine, through any study design, the association between an a
priori set of indicators related to the criminalisation of drugs and HIV
prevention or treatment among PWID; provide sufficient details on the methods
followed to allow critical assessment of quality; be published or presented
between Jan 1, 2006, and Dec 31, 2014; and be published in the English language.
FINDINGS: We identified 106 eligible studies comprising 29 longitudinal, 49 cross
sectional, 22 qualitative, two mixed methods, four mathematical modelling
studies, and no randomised controlled trials. 120 criminalisation indicators were
identified (range 1-3 per study) and 150 HIV indicators were identified (1-5 per
study). The most common criminalisation indicators were incarceration (n=38) and
street-level policing (n=39), while the most frequent HIV prevention and
treatment indicators were syringe sharing (n=35) and prevalence of HIV infection
among PWID (n=28). Among the 106 studies included in this review, 85 (80%)
suggested that drug criminalisation has a negative effect on HIV prevention and
treatment, 10 (9%) suggested no association, five (5%) suggested a beneficial
effect, one (1%) suggested both beneficial and negative effects, and five (5%)
suggested both null and negative effects. INTERPRETATION: These data confirm that
criminalisation of drug use has a negative effect on HIV prevention and
treatment. Our results provide an objective evidence base to support numerous
international policy initiatives to reform legal and policy frameworks
criminalising drug use. FUNDING: Canadian Institutes of Health Research and US
National Institutes of Health.
PMID- 28515018
TI - Plasma levels of the endocannabinoid anandamide, related N-acylethanolamines and
linoleic acid-derived oxylipins in patients with migraine.
AB - There is evidence that patients with migraine have deficient levels of the
endogenous cannabinoid receptor ligand anandamide (AEA). It is not known,
however, if this is a localised or generalised phenomenon. In the present study,
levels of AEA, related N-acylethanolamines (NAEs) and linoleic acid-derived
oxylipins have been measured in the blood of 26 healthy women and 38 women with
migraine (26 with aura, 12 without aura) who were matched for age and body-mass
index. Blood samples were taken on two occasions: the first sample near the start
of the menstrual cycle (when present) and the second approximately fourteen days
later. For a subset of migraine patients, two additional blood samples were
taken, one during a migraine attack and one approximately 1 month later (to be at
the same stage in the menstrual cycle, when present). NAEs and oxylipins were
measured by liquid chromatography coupled to mass spectrometry. Twenty-nine
lipids were quantified, of which 16 were found to have a high reproducibility of
measurement. There were no significant differences in the levels of AEA, the
related NAEs stearoylethanolamide and oleoylethanolamide or any of the nine
linoleic acid-derived oxylipins measured either between migraine patients with
vs. without aura, or between controls and migraine patients (after stratification
to take into account whether or not the individuals had regular menstruation
cycles) in either of the first two samples. Levels of linoleoylethanolamide were
lower in the patients with vs. without aura on the second sample but not in the
first sample, but the biological importance of this finding is unclear. Due to
time-dependent increases in their concentrations ex vivo prior to centrifugation,
AEA and oleoylethanolamide levels in the samples collected during migraine
attacks were not analysed, but for the other fourteen lipids, there were no
significant differences in plasma concentrations during migraine vs. one month
later. It is concluded that migraine is not associated with a generalised (as
opposed to localised) deficiency in these lipids.
PMID- 28515019
TI - Serum polyunsaturated fatty acid metabolites as useful tool for screening
potential biomarker of colorectal cancer.
AB - The biomarker identification of cancer is benefit for early detection and less
invasion. Polyunsaturated fatty acid (PUFA) metabolite as inflammatory mediators
can affect progression and treatment of cancer. In this work, the serum was
collected from colorectal cancer patients and healthy volunteers, and then we
tested the change of serum PUFA metabolites in both of them by ultra-high
performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Of the
158 PUFA and their metabolites, we found that abnormal change of 2, 3-dinor-8-iso
PGF2alpha, 19-HETE and 12-keto-LTB4 from arachidonic acid were observed in
colorectal cancer patients. Meanwhile, 9-HODE and 13-HODE from linoleic acid were
significant lower in colorectal cancer patients. Our data suggested that some
PUFA metabolites might be used as a potential biomarker of colorectal cancer,
which might provide assistance in clinical diagnosis and treatment.
PMID- 28515020
TI - Supplementation with high-dose docosahexaenoic acid increases the Omega-3 Index
more than high-dose eicosapentaenoic acid.
AB - BACKGROUND: Recent studies suggest that eicosapentaenoic (EPA) and
docosahexaenoic (DHA) acids have distinct effects on cardiometabolic risk
factors. The Omega-3 Index (O3I), which is calculated as the proportion of EPA
and DHA in red blood cell (RBC) membranes, has been inversely associated with the
risk of coronary heart diseases and coronary mortality. The objective of this
study was to compare the effects of EPA and DHA supplementation on the O3I in men
and women with abdominal obesity and subclinical inflammation. METHODS: In a
double-blind controlled crossover study, 48 men and 106 women with abdominal
obesity and subclinical inflammation were randomized to a sequence of three
treatment phases: 1-2.7g/d of EPA, 2-2.7g/d of DHA, and 3-3g/d of corn oil (0g of
EPA+DHA). All supplements were provided as 3*1g capsules for a total of 3g/d. The
10-week treatment phases were separated by nine-week washouts. RBC membrane fatty
acid composition and O3I were assessed at baseline and the end of each phase.
Differences in O3I between treatments were assessed using mixed models for
repeated measures. RESULTS: The increase in the O3I after supplementation with
DHA (+5.6% compared with control, P<0.0001) was significantly greater than after
EPA (+3.3% compared with control, P<0.0001; DHA vs. EPA, P<0.0001). Compared to
control, DHA supplementation decreased (-0.8%, P<0.0001) while EPA increased
(+2.5%, P<0.0001) proportion of docosapentaenoic acid (DPA) in RBCs (DHA vs. EPA,
P<0.0001). The baseline O3I was higher in women than in men (6.3% vs. 5.8%,
P=0.011). The difference between DHA and EPA in increasing the O3I tended to be
higher in men than in women (+2.6% vs. +2.2% respectively, P for the treatment by
sex interaction=0.0537). CONCLUSIONS: The increase in the O3I is greater with
high dose DHA supplementation than with high dose EPA, which is consistent with
the greater potency of DHA to modulate cardiometabolic risk factors. The extent
to which such differences between EPA and DHA in increasing the O3I relates to
long-term cardiovascular risk needs to be investigated in the future.
PMID- 28515021
TI - Sulforaphene, an isothiocyanate present in radish plants, inhibits proliferation
of human breast cancer cells.
AB - BACKGROUND: Isothiocyanates derived from the Brassicaceae plants possess
chemopreventive and anticancer activities. One of them is sulforaphene (SF),
which is abundant in Rhapanus sativus seeds. The underlying mechanism of its
anticancer activity is still underexplored. PURPOSE: SF properties make it an
interesting candidate for cancer prevention and therapy. Thus, it is crucial to
characterize the mechanism of its activity. STUDY DESIGN: We investigated the
mechanism of antiproliferative activity of SF in breast cancer cells differing in
growth factor receptors status and lacking functional p53. METHODS: Viability of
SKBR-3 and MDA-MB-231 breast cancer cells treated with SF was determined by SRB
and clonogenic assays. Cell cycle, cell death and oxidative stress were analyzed
by flow cytometry or microscopy. The levels of apoptosis and autophagy markers
were assessed by immunoblotting. RESULTS: SF efficiently decreased the viability
of breast cancer cells, while normal cells (MCF10A) were less sensitive to the
analyzed isothiocyanate. SF induced G2/M cell cycle arrest, as well as disturbed
cytoskeletal organization and reduced clonogenic potential of the cancer cells.
SF induced apoptosis in a concentration-dependent manner which was associated
with the oxidative stress, mitochondria dysfunction, increased Bax:Bcl2 ratio and
ADRP levels. SF also potentiated autophagy which played a cytoprotective role.
CONCLUSIONS: SF exhibits cytotoxic activity against breast cancer cells even at
relatively low concentrations (5-10uM). This is associated with induction of the
cell cycle arrest and apoptosis. SF might be considered as a potent anticancer
agent.
PMID- 28515023
TI - Corrigendum: Chikusetsusaponin IVa methyl ester induces G1 cell cycle arrest,
triggers apoptosis and inhibits migration and invasion in ovarian cancer cells.
Phytomedicine, 2016, 23(13): 1555-1565.
PMID- 28515022
TI - SOS response in bacteria: Inhibitory activity of lichen secondary metabolites
against Escherichia coli RecA protein.
AB - BACKGROUND: RecA is a bacterial multifunctional protein essential to genetic
recombination, error-prone replicative bypass of DNA damages and regulation of
SOS response. The activation of bacterial SOS response is directly related to the
development of intrinsic and/or acquired resistance to antimicrobials. Although
recent studies directed towards RecA inactivation via ATP binding inhibition
described a variety of micromolar affinity ligands, inhibitors of the DNA binding
site are still unknown. PURPOSE: Twenty-seven secondary metabolites classified as
anthraquinones, depsides, depsidones, dibenzofurans, diphenyl-butenolides,
paraconic acids, pseudo-depsidones, triterpenes and xanthones, were investigated
for their ability to inhibit RecA from Escherichia coli. They were isolated in
various Chilean regions from 14 families and 19 genera of lichens. METHODS: The
ATP hydrolytic activity of RecA was quantified detecting the generation of free
phosphate in solution. The percentage of inhibition was calculated fixing at
100uM the concentration of the compounds. Deeper investigations were reserved to
those compounds showing an inhibition higher than 80%. To clarify the mechanism
of inhibition, the semi-log plot of the percentage of inhibition vs. ATP and vs.
ssDNA, was evaluated. RESULTS: Only nine compounds showed a percentage of RecA
inhibition higher than 80% (divaricatic, perlatolic, alpha-collatolic, lobaric,
lichesterinic, protolichesterinic, epiphorellic acids, sphaerophorin and
tumidulin). The half-inhibitory concentrations (IC50) calculated for these
compounds were ranging from 14.2uM for protolichesterinic acid to 42.6uM for
sphaerophorin. Investigations on the mechanism of inhibition showed that all
compounds behaved as uncompetitive inhibitors for ATP binding site, with the
exception of epiphorellic acid which clearly acted as non-competitive inhibitor
of the ATP site. Further investigations demonstrated that epiphorellic acid
competitively binds the ssDNA binding site. Kinetic data were confirmed by
molecular modelling binding predictions which shows that epiphorellic acid is
expected to bind the ssDNA site into the L2 loop of RecA protein. CONCLUSION: In
this paper the first RecA ssDNA binding site ligand is described. Our study sets
epiphorellic acid as a promising hit for the development of more effective RecA
inhibitors. In our drug discovery approach, natural products in general and
lichen in particular, represent a successful source of active ligands and
structural diversity.
PMID- 28515024
TI - Knowledge, attitude, and practice towards blood donation among health care
providers in hospitals at Bahir Dar City, Ethiopia.
AB - Like other sub-Saharan Africa, in Ethiopia there is a shortage of adequate and
safe blood supplies. Health care providers are potential resource and promoter of
voluntary blood donation. This study was conducted to determine the knowledge,
attitude and practice towards blood donation among health care providers in Bahir
Dar City, Ethiopia. Paper based questionnaire was distributed to 276 health care
providers from May 01 to June 30, 2016. Overall, 42.8% had donated blood at least
once. Of these, males accounted for 60%. The median age of blood donors was 26
years. Voluntary-unpaid donation was 21.2%. Overall, 75.5% health care providers
were knowledgeable. The levels of knowledge were significantly different among
different disciplines (One-way ANOVA; F=69.7; P=0.004). Males were more
knowledgeable than females (P<0.05). The overall favorable attitude was 78.6%.
Previous practice of blood donation determined the odds of favorable attitude to
be a future regular voluntary-unpaid blood donor (OR: 5.7, 95% CI: 3.2-10.4).
Majority of health care providers had adequate knowledge and favorable attitude.
However, voluntary-unpaid donation practice (21.1%) was lower compared to 100%
target of voluntary-unpaid donation. There should be motivation packages to
enhance voluntary-unpaid blood donation among health care professionals.
PMID- 28515025
TI - Priority-setting and feasibility of health information exchange for primary care
patients with intellectual disabilities: A modified Delphi study.
AB - OBJECTIVE: Accurate health information exchange (HIE) is fragile in healthcare
for patients with intellectual disabilities (ID), threatening the health outcomes
for this patient group. In conjunction with a group of experts, we aimed to
identify the principal actions and organisational factors facilitating HIE for
primary care patients with ID and to assess their perceived feasibility in daily
practice. METHODS: We conducted a two-round modified Delphi study with Dutch GPs
(n=22), support workers (n=18) and ID physicians (n=20). In an extensive set of
61 items covering actions and organisational factors, experts ranked items in
order of importance and rated their feasibility. RESULTS: Agreement was reached
on the importance of 22 actions and eight organisational factors, of which 82%
were deemed (very) feasible in daily practice. Experts stressed the importance of
listed actions and factors being implemented simultaneously and remarked that
further priority should be based on contextual demands. CONCLUSION AND PRACTICE
IMPLICATIONS: This study indicates the principal actions and organisational
factors for HIE regarding primary care patients with ID. The set can be used as a
practical guide to optimise inter-professional cooperation and arrange the
distribution of HIE roles and responsibilities in relation to this patient group.
PMID- 28515026
TI - Corrigendum to ' Development of a prediction model for child maltreatment
recurrence in Japan: A historical cohort study using data from a Child Guidance
Center' Child Abuse & Neglect 59 (2016) 55-65.
PMID- 28515028
TI - Augmentation of the infraorbital rim in orthognathic surgery.
AB - Mid-face augmentation via a Le Fort I osteotomy is a commonly performed
operation. Advancement of the upper jaw and associated structures (nose, lower
cheek areas) can certainly improve function as well as facial aesthetics and
harmony. Often, in patients with severe mid-face deficiency, hypoplasia of the
maxilla extends all the way up to the infraorbital rims. The receding
infraorbital rim contributes to the negative vector of the globes. In patients
with this level of mid-face hypoplasia, while advancing the maxilla at the Le
Fort I level satisfies all of the requirements for orthognathic surgery, the
deficient infraorbital rim remains unchanged and can actually accentuate the
negative vector of the globes. This article explains our approach in augmentation
of the deficient infraorbital rim using alloplastic silicone implants at the time
of a Le Fort I osteotomy.
PMID- 28515027
TI - Early Versus Delayed Invasive Strategies in High-Risk Non-ST Elevation Acute
Coronary Syndrome Patients - A Systematic Literature Review and Meta-Analysis of
Randomised Controlled Trials.
AB - RATIONALE: It is unclear whether it is beneficial to perform angiography and/or
percutaneous coronary intervention (PCI) as an early or delayed invasive strategy
amongst high-risk non-ST elevation acute coronary syndrome (NSTEACS) patients.
OBJECTIVE: To determine whether an early invasive strategy could further reduce
recurrent myocardial infarction (MI) and early mortality compared to a delayed
invasive strategy. METHODS AND RESULTS: We searched MEDLINE, CINAHL and SCOPUS
and performed a meta-analysis of nine RCTs with a total of 5274 patients. No
statistically significant difference in recurrent MI (RR=0.56, 95% CI 0.17-1.87,
p=0.35), early mortality (RR=0.81, 95% CI 0.62-1.05, p=0.11) and major bleeding
(RR=0.85, 95% CI 0.66-1.09, p=0.21) was found between groups. A statistically
significant reduction in recurrent ischaemia was found amongst patients treated
with an early invasive strategy (RR 0.45, 95% CI 0.26-0.78, p=0.004). Subgroup
analysis for recurrent MI showed a statistically significant reduction in risk
amongst patients treated <24hours compared to>=24hours (RR=0.31, 95% CI 0.11
0.89, p=0.03). CONCLUSION: This study suggests that an early invasive strategy
may not further reduce recurrent MI and early mortality, but may significantly
reduce recurrent ischaemia. However, the recurrent MI endpoint was associated
with heterogeneity due to inconsistent MI definitions and strategy timings
amongst the included trials. Furthermore, subgroup analysis demonstrated a
significant reduction in recurrent MI amongst patients treated <24hours.
Therefore, large clinical trials with consistent inclusion criteria are required
to confirm whether intervention within 24hours reduces the rate of spontaneous
and post-discharge recurrent MI. Future studies with long-term follow-up data are
required to detect relevant differences in early mortality. Currently, it appears
that stabilised high-risk NSTEACS patients may be safely delayed up to 24hours
before undergoing an early invasive strategy.
PMID- 28515029
TI - Tolvaptan Treatment in Children with Chronic Hyponatremia due to Inappropriate
Antidiuretic Hormone Secretion: A Report of Three Cases
AB - Hyponatremia is the most common electrolyte disorder among hospitalized patients
and it is sometimes considered as a poor outcome predictor. Its correction is
thus indicated, even in asymptomatic patients. The conventional treatment
consists of fluid restriction in presence of euvolemia or hypervolemia; loop
diuretics are used in some hypervolemic conditions such as cardiac heart failure,
liver cirrhosis and nephrotic syndrome, while intravenous isotonic or hypertonic
solutions are administered in hypovolemic conditions. The utilization of
demeclocycline and urea is not indicated in pediatric ages due to lack of data on
their toxicity and poor tolerance. Recently, a new therapeutic option has been
developed, a class of non-peptide arginine vasopressin receptor antagonists
called vaptans. Tolvaptan is the only such agent approved in Europe for the
treatment of hyponatremia caused by syndrome of inappropriate antidiuretic
hormone secretion (SIADH) in adults. In USA, tolvaptan and conivaptan have been
approved for treatment of euvolemic and hypervolemic hyponatremia. Few data are
so far available in paediatric patients, since only one trial has been registered
in Europe which includes children and adolescents, but this trial is still
ongoing. Here, we report three children with chronic hyponatremia due to SIADH in
which tolvaptan has been used successfully.
PMID- 28515030
TI - Congenital Central Hypothyroidism Caused by a Novel Thyroid-Stimulating Hormone
Beta Subunit Gene Mutation in Two Siblings.
AB - Congenital central hypothyroidism (CCH) is a very rare disease. Alterations in
pituitary development genes as well as mutations of immunoglobulin superfamily
member 1 and transducin beta-like protein 1 can result in CCH and multiple
pituitary hormone deficiencies. However, mutations of the thyrotropin-releasing
hormone receptor or thyroid-stimulating hormone-beta (TSHB) gene are responsible
for isolated CCH. In this paper, we present the cases of two siblings with a
novel mutation of TSHB. Direct sequencing of the coding regions and exon/intron
boundaries of the TSHB gene revealed two homozygous nucleotides changes. One of
them was c.40A>G (rs10776792) which is a very common variation that is also seen
in healthy individuals, the other was c.94G>A at codon 32 of exon 2 which
resulted in a change from glutamic acid to lysine (p.E32K). Both patients were
homozygous and the parents were heterozygous.
PMID- 28515032
TI - WITHDRAWN: Bilateral painless testicular mass, acute uveitis and annular
cutaneous lesions: an unusual presentation of sarcoidosis and literature review.
AB - Ahead of Print article withdrawn by publisher.
PMID- 28515031
TI - Phenotypic Variability in a Family with Acrodysostosis Type 2 Caused by a Novel
PDE4D Mutation Affecting the Serine Target of Protein Kinase-A Phosphorylation.
AB - Acrodysostosis is a very rare congenital multisystem condition characterized by
skeletal dysplasia with severe brachydactyly, midfacial hypoplasia, and short
stature, varying degrees of intellectual disability, and possible resistance to
multiple G protein-coupled receptor signalling hormones. Two distinct subtypes
are differentiated: acrodysostosis type 1 resulting from defects in protein
kinase type 1-alpha regulatory subunit and acrodysostosis type 2 caused by
mutations in phosphodiesterase 4D (PDE4D). Most cases are sporadic. We report on
a rare multigenerational familial case of acrodysostosis type 2 due to a novel
autosomal dominantly inherited PDE4D mutation. A 3.5-year-old boy presented with
short stature, midfacial hypoplasia, severe brachydactyly, developmental delay,
and behavioural problems. Laboratory investigations revealed mild thyrotropin
resistance. His mother shared some characteristic features, such as midfacial
hypoplasia and severe brachydactyly, but did not show short stature, intellectual
disability or hormonal resistance. Genetic analysis identified the identical,
novel heterozygous missense mutation of the PDE4D gene c.569C>T (p.Ser190Phe) in
both patients. This case illustrates the significant phenotypic variability of
acrodysostosis even within one family with identical mutations. Hence, a specific
clinical diagnosis of acrodysostosis remains challenging because of great
interindividual variability and a substantial overlap of the two subtypes as well
as with other related Gsalpha-cAMP-signalling-linked disorders.
PMID- 28515033
TI - Acanthocytosis and HyperCKemia
PMID- 28515035
TI - Ray Dolan: Blues on the brain.
PMID- 28515034
TI - Wrist Circumference and Frame Size Percentiles in 6-17-Year-Old Turkish Children
and Adolescents in Kayseri.
AB - OBJECTIVE: The aim of the current study was to provide wrist circumference (WrC)
and body frame size (height/WrC) percentile values in Turkish children and
adolescents aged 6-17 years. METHODS: In this cross-sectional study, the data of
"Determination of Anthropometric Measures of Turkish Children and Adolescents"
(DAMTCA II) study in Kayseri/Turkey were used. A total of 4330 observations were
recorded (1931 boys, 2399 girls). The WrC and frame size reference values were
produced with generalized additive models for location, scale and shape. RESULTS:
The WrC percentiles (3rd-97th) were calculated. The frame size (height/WrC) was
estimated as small, medium, and large (<15th, 15-85th, and >=85th percentiles,
respectively). For both genders, WrC linearly increased with age (13.0-16.8 cm
for boys and 12.5-15.5 cm for girls). In boys and girls, the mean +/- standard
deviation of WrC is 13.00+/-0.89 cm and 12.48+/-0.93 cm (6 years) and increases
to 16.83+/-1.16 and 15.58+/-0.86 cm (17 years), respectively. The WrC values in
all age groups were higher in boys compared with girls. The increment in frame
size from 6 to 17 years were 1.25 cm in boys and 0.85 cm in girls. CONCLUSION:
WrC is a simple, easy-to-detect anthropometric index which is not subject to
measurement errors. Additionally, WrC can be used both to decide about frame size
and to determine metabolic risks related to obesity. We consider that this easy
to-get anthropometric index can be used both in screening procedures and clinical
assessment procedure for obesity-related metabolic consequences.
PMID- 28515038
TI - Simon Stevens uses art to sidestep purdah.
PMID- 28515037
TI - Labour's pledge to boost NHS funding by L30bn is "still not enough".
PMID- 28515040
TI - A systematic review of overlapping microRNA patterns in systemic sclerosis and
idiopathic pulmonary fibrosis.
AB - Lung fibrosis can be observed in systemic sclerosis and in idiopathic pulmonary
fibrosis, two disorders where lung involvement carries a poor prognosis. Although
much has been learned about the pathogenesis of these conditions, interventions
capable of reversing or, at the very least, halting disease progression are not
available. Recent studies point to the potential role of micro messenger RNAs
(microRNAs) in cancer and tissue fibrogenesis. MicroRNAs are short non-coding RNA
sequences (20-23 nucleotides) that are endogenous, evolutionarily conserved and
encoded in the genome. By acting on several genes, microRNAs control protein
expression. Considering the above, we engaged in a systematic review of the
literature in search of overlapping observations implicating microRNAs in the
pathogenesis of both idiopathic pulmonary fibrosis (IPF) and systemic sclerosis
(SSc). Our objective was to uncover top microRNA candidates for further
investigation based on their mechanisms of action and their potential for serving
as targets for intervention against lung fibrosis. Our review points to microRNAs
of the -29 family, -21-5p and -92a-3p, -26a-5p and let-7d-5p as having distinct
and counter-balancing actions related to lung fibrosis. Based on this, we
speculate that readjusting the disrupted balance between these microRNAs in lung
fibrosis related to SSc and IPF may have therapeutic potential.
PMID- 28515041
TI - Multidisciplinary evaluation of interstitial lung diseases: current insights:
Number 1 in the Series "Radiology" Edited by Nicola Sverzellati and Sujal Desai.
AB - Multidisciplinary team (MDT) diagnosis is regarded as the diagnostic reference
standard for interstitial lung disease (ILD). Several studies have reported that
MDT diagnosis is associated with higher levels of diagnostic confidence and
better interobserver agreement when compared to the individual components of the
MDT in isolation. Although this recommendation is widely accepted, no guideline
statement specifies what constitutes an MDT meeting and how its participants
should govern it. Furthermore, the precise role of an MDT meeting in the setting
of ILD may vary from one group to another. For example, in some cases, the
meeting will confine its discussion to characterising the disease and formulating
diagnosis. In others, management decisions may also be part of the discussion.
Surprisingly, there is no consensus on how MDT diagnosis is validated. As
multidisciplinary evaluation contains all the available clinical information on
an individual patient, there is no reference standard against which the veracity
of MDT diagnosis can be tested. Finally, many of these uncertainties surrounding
MDT meeting practice are unlikely to be answered by traditional evidence-based
studies, which create difficulties when generating guideline recommendations.
There is clearly a need for expert consensus on what constitutes acceptable MDT
meeting practice. This consensus will need to be flexible to accommodate the
variability in resources available to fledgling MDT groups and the variable
nature of patients requiring discussion.
PMID- 28515042
TI - Radiology in diffuse parenchymal lung disease and lung nodules.
PMID- 28515045
TI - Private sector should have same safety rigour as NHS, say surgeons after Paterson
conviction.
PMID- 28515044
TI - Exploring the Causal Pathway From Telomere Length to Coronary Heart Disease: A
Network Mendelian Randomization Study.
AB - RATIONALE: Observational studies have found shorter leukocyte telomere length
(TL) to be a risk factor for coronary heart disease (CHD), and recently the
association was suggested to be causal. However, the relationship between TL and
common metabolic risk factors for CHD is not well understood. Whether these risk
factors could explain pathways from TL to CHD warrants further attention.
OBJECTIVE: To examine whether metabolic risk factors for CHD mediate the causal
pathway from short TL to increased risk of CHD using a network Mendelian
randomization design. METHODS AND RESULTS: Summary statistics from several genome
wide association studies were used in a 2-sample Mendelian randomization study
design. Network Mendelian randomization analysis-an approach using genetic
variants as the instrumental variables for both the exposure and mediator to
infer causality-was performed to examine the causal association between telomeres
and CHD and metabolic risk factors. Summary statistics from the ENGAGE Telomere
Consortium were used (n=37 684) as a TL genetic instrument, CARDIoGRAMplusC4D
Consortium data were used (case=22 233 and control=64 762) for CHD, and other
consortia data were used for metabolic traits (fasting insulin, triglyceride,
total cholesterol, low-density lipoprotein cholesterol, fasting glucose, diabetes
mellitus, glycohemoglobin, body mass index, waist circumference, and waist:hip
ratio). One-unit increase of genetically determined TL was associated with -0.07
(95% confidence interval, -0.01 to -0.12; P=0.01) lower log-transformed fasting
insulin (pmol/L) and 21% lower odds (95% confidence interval, 3-35; P=0.02) of
CHD. Higher genetically determined log-transformed fasting insulin level was
associated with higher CHD risk (odds ratio, 1.86; 95% confidence interval, 1.01
3.41; P=0.04). CONCLUSIONS: Overall, our findings support a role of insulin as a
mediator on the causal pathway from shorter telomeres to CHD pathogenesis.
PMID- 28515043
TI - Brain Perivascular Macrophages Initiate the Neurovascular Dysfunction of
Alzheimer Abeta Peptides.
AB - RATIONALE: Increasing evidence indicates that alterations of the cerebral
microcirculation may play a role in Alzheimer disease, the leading cause of late
life dementia. The amyloid-beta peptide (Abeta), a key pathogenic factor in
Alzheimer disease, induces profound alterations in neurovascular regulation
through the innate immunity receptor CD36 (cluster of differentiation 36), which,
in turn, activates a Nox2-containing NADPH oxidase, leading to cerebrovascular
oxidative stress. Brain perivascular macrophages (PVM) located in the
perivascular space, a major site of brain Abeta collection and clearance, are
juxtaposed to the wall of intracerebral resistance vessels and are a powerful
source of reactive oxygen species. OBJECTIVE: We tested the hypothesis that PVM
are the main source of reactive oxygen species responsible for the
cerebrovascular actions of Abeta and that CD36 and Nox2 in PVM are the molecular
substrates of the effect. METHODS AND RESULTS: Selective depletion of PVM using
intracerebroventricular injection of clodronate abrogates the reactive oxygen
species production and cerebrovascular dysfunction induced by Abeta applied
directly to the cerebral cortex, administered intravascularly, or overproduced in
the brain of transgenic mice expressing mutated forms of the amyloid precursor
protein (Tg2576 mice). In addition, using bone marrow chimeras, we demonstrate
that PVM are the cells expressing CD36 and Nox2 responsible for the dysfunction.
Thus, deletion of CD36 or Nox2 from PVM abrogates the deleterious vascular
effects of Abeta, whereas wild-type PVM reconstitute the vascular dysfunction in
CD36-null mice. CONCLUSIONS: The data identify PVM as a previously unrecognized
effector of the damaging neurovascular actions of Abeta and unveil a new
mechanism by which brain-resident innate immune cells and their receptors may
contribute to the pathobiology of Alzheimer disease.
PMID- 28515046
TI - KIF1B and NF1 are the most frequently mutated genes in paraganglioma and
pheochromocytoma tumors.
PMID- 28515048
TI - Essential Function of the Serine Hydroxymethyl Transferase (SHMT) Gene During
Rapid Syncytial Cell Cycles in Drosophila.
AB - Many metabolic enzymes are evolutionarily highly conserved and serve a central
function in the catabolism and anabolism of cells. The serine hydroxymethyl
transferase (SHMT) catalyzing the conversion of serine and glycine and vice versa
feeds into tetrahydrofolate (THF)-mediated C1 metabolism. We identified a
Drosophila mutation in SHMT (CG3011) in a screen for blastoderm mutants. Embryos
from SHMT mutant germline clones specifically arrest the cell cycle in interphase
13 at the time of the midblastula transition (MBT) and prior to cellularization.
The phenotype is due to a loss of enzymatic activity as it cannot be rescued by
an allele with a point mutation in the catalytic center but by an allele based on
the SHMT coding sequence from Escherichia coli The onset of zygotic gene
expression and degradation of maternal RNAs in SHMT mutant embryos are largely
similar to that in wild-type embryos. The specific timing of the defects in SHMT
mutants indicates that at least one of the SHMT-dependent metabolites becomes
limiting in interphase 13, if it is not produced by the embryo. Our data suggest
that mutant eggs contain maternally-provided and SHMT-dependent metabolites in
amounts that suffice for early development until interphase 13.
PMID- 28515050
TI - The Mapping of Predicted Triplex DNA:RNA in the Drosophila Genome Reveals a
Prominent Location in Development- and Morphogenesis-Related Genes.
AB - Double-stranded DNA is able to form triple-helical structures by accommodating a
third nucleotide strand. A nucleic acid triplex occurs according to Hoogsteen
rules that predict the stability and affinity of the third strand bound to the
Watson-Crick duplex. The "triplex-forming oligonucleotide" (TFO) can be a short
sequence of RNA that binds to the major groove of the targeted duplex only when
this duplex presents a sequence of purine or pyrimidine bases in one of the DNA
strands. Many nuclear proteins are known to bind triplex DNA or DNA:RNA, but
their biological functions are unexplored. We identified sequences that are
capable of engaging as the "triplex-forming oligonucleotide" in both the pre
lncRNA and pre-mRNA collections of Drosophila melanogaster These motifs were
matched against the Drosophila genome in order to identify putative sequences of
triplex formation in intergenic regions, promoters, and introns/exons. Most of
the identified TFOs appear to be located in the intronic region of the analyzed
genes. Computational prediction of the most targeted genes by TFOs originating
from pre-lncRNAs and pre-mRNAs revealed that they are restrictively associated
with development- and morphogenesis-related gene networks. The refined analysis
by Gene Ontology enrichment demonstrates that some individual TFOs present genome
wide scale matches that are located in numerous genes and regulatory sequences.
The triplex DNA:RNA computational mapping at the genome-wide scale suggests broad
interference in the regulatory process of the gene networks orchestrated by TFO
RNAs acting in association simultaneously at multiple sites.
PMID- 28515051
TI - Understanding and supporting women with polycystic ovary syndrome: a qualitative
study in an ethnically diverse UK sample.
AB - OBJECTIVE: Polycystic ovary syndrome (PCOS) is a lifelong condition. Its symptoms
have been linked with psychological consequences, but less attention has been
given to the daily implications of living with PCOS. We aimed to explore women's
experiences living with PCOS, and the potential acceptability of group education
sessions for this target group. METHODS: Women with PCOS were recruited from an
ethnically diverse UK community. Twelve semi-structured interviews were
conducted. Analysis was underpinned by the constant comparative approach and
involved the identification and exploration of key themes. RESULTS: Participants
reported a range of symptoms linked with PCOS, including problems relating to
menstruation and weight difficulties. Hirsutism was reported as the most
distressing symptom. Emergent themes included perceptions about symptoms and
delays in receiving a diagnosis; psychological distress; practical implications
of living with the condition; coping with PCOS and perceived support needs. Some
findings were specific to cultural backgrounds. Participants were supportive of
the idea of group education for women with PCOS and suggested a need to provide
education within the community and health care providers. DISCUSSION: Women with
PCOS experience high psychological distress and difficulties with coping with
their condition. Suggested strategies to reduce the negative psychological impact
include education at various levels.
PMID- 28515049
TI - A Generalized Linear Model for Decomposing Cis-regulatory, Parent-of-Origin, and
Maternal Effects on Allele-Specific Gene Expression.
AB - Joint quantification of genetic and epigenetic effects on gene expression is
important for understanding the establishment of complex gene regulation systems
in living organisms. In particular, genomic imprinting and maternal effects play
important roles in the developmental process of mammals and flowering plants.
However, the influence of these effects on gene expression are difficult to
quantify because they act simultaneously with cis-regulatory mutations. Here we
propose a simple method to decompose cis-regulatory (i.e., allelic genotype),
genomic imprinting [i.e., parent-of-origin (PO)], and maternal [i.e., maternal
genotype (MG)] effects on allele-specific gene expression using RNA-seq data
obtained from reciprocal crosses. We evaluated the efficiency of method using a
simulated dataset and applied the method to whole-body Drosophila and mouse
trophoblast stem cell (TSC) and liver RNA-seq data. Consistent with previous
studies, we found little evidence of PO and MG effects in adult Drosophila
samples. In contrast, we identified dozens and hundreds of mouse genes with
significant PO and MG effects, respectively. Interestingly, a similar number of
genes with significant PO effect were detect in mouse TSCs and livers, whereas
more genes with significant MG effect were observed in livers. Further
application of this method will clarify how these three effects influence gene
expression levels in different tissues and developmental stages, and provide
novel insight into the evolution of gene expression regulation.
PMID- 28515047
TI - Centrosome amplification: a suspect in breast cancer and racial disparities.
AB - The multifaceted involvement of centrosome amplification (CA) in tumorigenesis is
coming into focus following years of meticulous experimentation, which have
elucidated the powerful abilities of CA to promote cellular invasion, disrupt
stem cell division, drive chromosomal instability (CIN) and perturb tissue
architecture, activities that can accelerate tumor progression. Integration of
the extant in vitro, in vivo and clinical data suggests that in some tissues CA
may be a tumor-initiating event, in others a consequential 'hit' in multistep
tumorigenesis, and in some others, non-tumorigenic. However, in vivo data are
limited and primarily focus on PLK4 (which has CA-independent mechanisms by which
it promotes aggressive cellular phenotypes). In vitro breast cancer models
suggest that CA can promote tumorigenesis in breast cancer cells in the setting
of p53 loss or mutation, which can both trigger CA and promote cellular tolerance
to its tendency to slow proliferation and induce aneuploidy. It is thus our
perspective that CA is likely an early hit in multistep breast tumorigenesis that
may sometimes be lost to preserve aggressive karyotypes acquired through
centrosome clustering-mediated CIN, both numerical and structural. We also
envision that the robust link between p53 and CA may underlie, to a considerable
degree, racial health disparity in breast cancer outcomes. This question is
clinically significant because, if it is true, then analysis of centrosomal
profiles and administration of centrosome declustering drugs could prove highly
efficacious in risk stratifying breast cancers and treating African American (AA)
women with breast cancer.
PMID- 28515052
TI - Exercise training improves free testosterone in lifelong sedentary aging men.
AB - As the impact of high-intensity interval training (HIIT) on systemic hormones in
aging men is unstudied to date, we investigated whether total testosterone (TT),
sex hormone-binding globulin (SHBG), free testosterone (free-T) and cortisol (all
in serum) were altered following HIIT in a cohort of 22 lifelong sedentary (62 +/
2 years) older men. As HIIT requires preconditioning exercise in sedentary
cohorts, participants were tested at three phases, each separated by six-week
training; baseline (phase A), following conditioning exercise (phase B) and post
HIIT (phase C). Each measurement phase used identical methods. TT was
significantly increased following HIIT (~17%; P < 0.001) with most increase
occurring during preconditioning (~10%; P = 0.007). Free-T was unaffected by
conditioning exercise (P = 0.102) but was significantly higher following HIIT
compared to baseline (~4.5%; P = 0.023). Cortisol remained unchanged from A to C
(P = 0.138). The present data indicate a combination of preconditioning, and HIIT
increases TT and SHBG in sedentary older males, with the HIIT stimulus accounting
for a small but statistically significant increase in free-T. Further study is
required to determine the biological importance of small improvements in free-T
in aging men.
PMID- 28515053
TI - Berberine reduced blood pressure and improved vasodilation in diabetic rats.
AB - Hyperglycemia and hypertension are considered to be the two leading risk factors
for vascular disease in diabetic patients. However, few pharmacologic agents
could provide a combinational therapy for controlling hyperglycemia and
hypertension at the same time in diabetes. The objectives of this study are to
investigate whether berberine treatment could directly reduce blood pressure and
identify the molecular mechanism underlying the vascular protection of berberine
in diabetic rats. Berberine was intragastrically administered with different
dosages of 50, 100 and 200 mg/kg/day to diabetic rats for 8 weeks since the
injection of streptozotocin. The endothelium-dependent/-independent relaxation in
middle cerebral arteries was investigated. The activity of large-conductance Ca2+
activated K+ channel (BKCa) was investigated by recording whole-cell currents,
analyzing single-channel activities and assessing the expressions of alpha- and
beta1-subunit at protein or mRNA levels. Results of the study suggest that
chronic administration of 100 mg/kg/day berberine not only lowered blood glucose
but also reduced blood pressure and improved vasodilation in diabetic rats.
Furthermore, berberine markedly increased the function and expression of BKCa
beta1-subunit in cerebral vascular smooth muscle cells (VSMCs) isolated from
diabetic rats or when exposed to hyperglycemia condition. The present study
provided initial evidences that berberine reduced blood pressure and improved
vasodilation in diabetic rats by activation of BKCa channel in VSMCs, which
suggested that berberine might provide a combinational therapy for controlling
hyperglycemia and blood pressure in diabetes. Furthermore, our work indicated
that activation of BKCa channel might be the underlying mechanism responsible for
the vascular protection of berberine in diabetes.
PMID- 28515054
TI - Longitudinal decline in lung function among older construction workers.
AB - BACKGROUND: Occupational exposures to vapours, gasses, dusts and fumes (VGDF) and
chest X-ray abnormalities by the International Labour Office (ILO) classification
system are associated with reduced lung function, with the majority of published
studies being cross-sectional. We examined the effects of VGDF exposures, as well
as ILO parenchymal changes, pleural plaque and diffuse pleural thickening (DPT)
on reduction in lung function in a longitudinal study. METHODS: Chest radiographs
and spirometry for 3150 ageing construction workers enrolled in a medical
screening programme with a baseline and at least one follow-up examination were
studied. Indices for VGDF exposure, parenchymal changes, pleural plaque and DPT
severity were developed and used in longitudinal mixed models of lung function.
RESULTS: Smoking and VGDF exposure were associated with decreased FEV1 and FVC at
baseline as well as accelerated rates of annual decline. High VGDF exposure was
associated with a yearly decline of -19.5 mL for FEV1 and -15.7 mL for FVC.
Parenchymal abnormalities, pleural plaque and DPT were more strongly associated
with reduced FVC. An increase of one unit in the pleural plaque severity index
resulted in approximately -5.3 mL loss of FVC and -3.3 mL loss of FEV1, with a
possible non-linear effect of plaque on FEV1. CONCLUSIONS: Increasing pleural
plaque severity was associated with progressively greater loss of FVC and FEV1,
supporting a causal association. VGDF exposures were associated with reduced FVC
and FEV1 at baseline as well as accelerated annual loss of lung function.
PMID- 28515056
TI - Reducing musculoskeletal injury and concussion risk in schoolboy rugby players
with a pre-activity movement control exercise programme: a cluster randomised
controlled trial.
AB - BACKGROUND: Injury risk in youth rugby has received much attention, highlighting
the importance of establishing evidence-based injury reduction strategies. AIM:
To determine the efficacy of a movement control exercise programme in reducing
injuries in youth rugby players and to investigate the effect of programme dose
on injury measures. METHODS: In a cluster-randomised controlled trial, 40
independent schools (118 teams, 3188 players aged 14-18 years) were allocated to
receive either the intervention or a reference programme, both of which were to
be delivered by school coaches. The intervention comprised balance training,
whole-body resistance training, plyometric training, and controlled rehearsal of
landing and cutting manoeuvres. Time-loss (>24 hours) injuries arising from
school rugby matches were recorded by coaches and medical staff. RESULTS: 441
time-loss match injuries (intervention, 233; control, 208) were reported across
15 938 match exposure-hours (intervention, 9083; control, 6855). Intention-to
treat results indicated unclear effects of trial arm on overall match injury
incidence (rate ratio (RR)=0.85, 90% confidence limits 0.61 to 1.17), although
clear reductions were evident in the intervention arm for concussion incidence
(RR=0.71, 0.48 to 1.05). When trial arm comparisons were limited to teams who had
completed three or more weekly programme sessions on average, clear reductions in
overall match injury incidence (RR=0.28, 0.14 to 0.51) and concussion incidence
(RR=0.41, 0.17 to 0.99) were noted in the intervention group. CONCLUSION: A
preventive movement control exercise programme can reduce match injury outcomes,
including concussion, in schoolboy rugby players when compared with a
standardised control exercise programme, although to realise the greatest effects
players should complete the programme at least three times per week.
PMID- 28515058
TI - Tissue-engineered cartilage constructed by a biotin-conjugated anti-CD44 avidin
binding technique for the repairing of cartilage defects in the weight-bearing
area of knee joints in pigs.
AB - OBJECTIVES: The lack of effective treatment for cartilage defects has prompted
investigations using tissue engineering techniques for their regeneration and
repair. The success of tissue-engineered repair of cartilage may depend on the
rapid and efficient adhesion of transplanted cells to a scaffold. Our aim in this
study was to repair full-thickness defects in articular cartilage in the weight
bearing area of a porcine model, and to investigate whether the CD44 monoclonal
antibody biotin-avidin (CBA) binding technique could provide satisfactory tissue
engineered cartilage. METHODS: Cartilage defects were created in the load-bearing
region of the lateral femoral condyle of mini-type pigs. The defects were
repaired with traditional tissue-engineered cartilage, tissue-engineered
cartilage constructed with the biotin-avidin (BA) technique, tissue-engineered
cartilage constructed with the CBA technique and with autologous cartilage. The
biomechanical properties, Western blot assay, histological findings and
immunohistochemical staining were explored. RESULTS: The CBA group showed similar
results to the autologous group in biomechanical properties, Moran's criteria,
histological tests and Wakitani histological scoring. CONCLUSIONS: These results
suggest that tissue-engineered cartilage constructed using the CBA technique
could be used effectively to repair cartilage defects in the weight-bearing area
of joints.Cite this article: H. Lin, J. Zhou, L. Cao, H. R. Wang, J. Dong, Z. R.
Chen. Tissue-engineered cartilage constructed by a biotin-conjugated anti-CD44
avidin binding technique for the repairing of cartilage defects in the weight
bearing area of knee joints in pigs. Bone Joint Res 2017;6:-295. DOI:
10.1302/2046-3758.65.BJR-2016-0277.
PMID- 28515057
TI - Delaying ACL reconstruction and treating with exercise therapy alone may alter
prognostic factors for 5-year outcome: an exploratory analysis of the KANON
trial.
AB - AIM: Identify injury-related, patient-reported and treatment-related prognostic
factors for 5-year outcomes in acutely ACL-ruptured individuals managed with
early reconstruction plus exercise therapy, exercise therapy plus delayed
reconstruction or exercise therapy alone. METHODS: Exploratory analysis of the
Knee Anterior Cruciate Ligament, Nonsurgical versus Surgical Treatment (KANON)
trial (ISRCTN84752559). Relationships between prognostic factors (baseline
cartilage, meniscus and osteochondral damage, baseline extension deficit,
baseline patient-reported outcomes, number of rehabilitation visits,
graft/contralateral ACL rupture, non-ACL surgery and ACL treatment strategy) and
5-year Knee Injury and Osteoarthritis Outcome Score (KOOS) pain, symptoms,
sport/recreation and quality of life (QOL) scores were explored using
multivariable linear regression. Estimates were adjusted for sex, age, body mass
index, preinjury activity level, education and smoking. RESULTS: For all
participants (n=118), graft/contralateral ACL rupture, non-ACL surgery and worse
baseline 36-item Short-Form Mental Component Scores were associated with worse
outcomes. Treatment with exercise therapy alone was a prognostic factor for less
knee symptoms compared with early reconstruction plus exercise therapy
(regression coefficient 10.1, 95% CI 2.3 to 17.9). Baseline meniscus lesion was
associated with worse sport/recreation function (-14.4, 95% CI -27.6 to -1.3) and
osteochondral lesions were associated with worse QOL (-12.3, 95% CI -24.3 to
0.4) following early reconstruction plus exercise therapy. In the same group,
undergoing additional non-ACL surgery and worse baseline KOOS scores were
prognostic for worse outcome on all KOOS subscales. Following delayed
reconstruction, baseline meniscus damage was a prognostic factor for less pain
(14.3, 95% CI 0.7 to 27.9). Following exercise therapy alone, undergoing non-ACL
surgery was prognostic for worse pain. CONCLUSIONS: Treatment-dependent
differences in prognostic factors for 5-year outcomes may support individualised
treatment after acute ACL rupture in young active individuals. TRIAL REGISTRATION
NUMBER: Current Controlled Trials ISRCTN84752559.
PMID- 28515055
TI - Exome Sequencing of African-American Prostate Cancer Reveals Loss-of-Function ERF
Mutations.
AB - African-American men have the highest incidence of and mortality from prostate
cancer. Whether a biological basis exists for this disparity remains unclear.
Exome sequencing (n = 102) and targeted validation (n = 90) of localized primary
hormone-naive prostate cancer in African-American men identified several gene
mutations not previously observed in this context, including recurrent loss-of
function mutations in ERF, an ETS transcriptional repressor, in 5% of cases.
Analysis of existing prostate cancer cohorts revealed ERF deletions in 3% of
primary prostate cancers and mutations or deletions in ERF in 3% to 5% of lethal
castration-resistant prostate cancers. Knockdown of ERF confers increased
anchorage-independent growth and generates a gene expression signature associated
with oncogenic ETS activation and androgen signaling. Together, these results
suggest that ERF is a prostate cancer tumor-suppressor gene. More generally, our
findings support the application of systematic cancer genomic characterization in
settings of broader ancestral diversity to enhance discovery and, eventually,
therapeutic applications.Significance: Systematic genomic sequencing of prostate
cancer in African-American men revealed new insights into prostate cancer,
including the identification of ERF as a prostate cancer gene; somatic copy
number alteration differences; and uncommon PIK3CA and PTEN alterations. This
study highlights the importance of inclusion of underrepresented minorities in
cancer sequencing studies. Cancer Discov; 7(9); 973-83. (c)2017 AACR.This article
is highlighted in the In This Issue feature, p. 920.
PMID- 28515059
TI - Antibiotic stability over six weeks in aqueous solution at body temperature with
and without heat treatment that mimics the curing of bone cement.
AB - OBJECTIVES: Thermal stability is a key property in determining the suitability of
an antibiotic agent for local application in the treatment of orthopaedic
infections. Despite the fact that long-term therapy is a stated goal of novel
local delivery carriers, data describing thermal stability over a long period are
scarce, and studies that avoid interference from specific carrier materials are
absent from the orthopaedic literature. METHODS: In this study, a total of 38
frequently used antibiotic agents were maintained at 37 degrees C in saline
solution, and degradation and antibacterial activity assessed over six weeks. The
impact of an initial supplementary heat exposure mimicking exothermically curing
bone cement was also tested as this material is commonly used as a local delivery
vehicle. Antibiotic degradation was assessed by liquid chromatography coupled to
mass spectrometry, or by immunoassays, as appropriate. Antibacterial activity
over time was determined by the Kirby-Bauer disk diffusion assay. RESULTS: The
heat exposure mimicking curing bone cement had minimal effect on stability for
most antibiotics, except for gentamicin which experienced approximately 25%
degradation as measured by immunoassay. Beta-lactam antibiotics were found to
degrade quite rapidly at 37 degrees C regardless of whether there was an initial
heat exposure. Excellent long-term stability was observed for aminoglycosides,
glycopeptides, tetracyclines and quinolones under both conditions. CONCLUSIONS:
This study provides a valuable dataset for orthopaedic surgeons considering local
application of antibiotics, and for material scientists looking to develop next
generation controlled or extended-release antibiotic carriers.Cite this article:
E. Samara, T. F. Moriarty, L. A. Decosterd, R. G. Richards, E. Gautier, P. Wahl.
Antibiotic stability over six weeks in aqueous solution at body temperature with
and without heat treatment that mimics the curing of bone cement. Bone Joint J
2017;6:296-306. DOI: 10.1302/2046-3758.65.BJR-2017-0276.R1.
PMID- 28515061
TI - Is there a better way to set population iron recommendations?
PMID- 28515060
TI - Barriers and facilitators experienced in collaborative prospective research in
orthopaedic oncology: A qualitative study.
AB - OBJECTIVES: As tumours of bone and soft tissue are rare, multicentre prospective
collaboration is essential for meaningful research and evidence-based advances in
patient care. The aim of this study was to identify barriers and facilitators
encountered in large-scale collaborative research by orthopaedic oncological
surgeons involved or interested in prospective multicentre collaboration.
METHODS: All surgeons who were involved, or had expressed an interest, in the
ongoing Prophylactic Antibiotic Regimens in Tumour Surgery (PARITY) trial were
invited to participate in a focus group to discuss their experiences with
collaborative research in this area. The discussion was digitally recorded,
transcribed and anonymised. The transcript was analysed qualitatively, using an
analytic approach which aims to organise the data in the language of the
participants with little theoretical interpretation. RESULTS: The 13 surgeons who
participated in the discussion represented orthopaedic oncology practices from
seven countries (Argentina, Brazil, Italy, Spain, Denmark, United States and
Canada). Four categories and associated themes emerged from the discussion: the
need for collaboration in the field of orthopaedic oncology due to the rarity of
the tumours and the need for high level evidence to guide treatment; motivational
factors for participating in collaborative research including establishing proof
of principle, learning opportunity, answering a relevant research question and
being part of a collaborative research community; barriers to participation
including funding, personal barriers, institutional barriers, trial barriers, and
administrative barriers and facilitators for participation including
institutional facilitators, leadership, authorship, trial set-up, and the support
of centralised study coordination. CONCLUSIONS: Orthopaedic surgeons involved in
an ongoing international randomised controlled trial (RCT) were motivated by many
factors to participate. There were a number of barriers to and facilitators for
their participation. There was a collective sense of fatigue experienced in
overcoming these barriers, which was mirrored by a strong collective sense of the
importance of, and need for, collaborative research in this field. The
experiences were described as essential educational first steps to advance
collaborative studies in this area. Knowledge gained from this study will inform
the development of future large-scale collaborative research projects in
orthopaedic oncology.Cite this article: J. S. Rendon, M. Swinton, N. Bernthal, M.
Boffano, T. Damron, N. Evaniew, P. Ferguson, M. Galli Serra, W. Hettwer, P.
McKay, B. Miller, L. Nystrom, W. Parizzia, P. Schneider, A. Spiguel, R. Velez, K.
Weiss, J. P. Zumarraga, M. Ghert. Barriers and facilitators experienced in
collaborative prospective research in orthopaedic oncology: A qualitative study.
Bone Joint Res 2017;6:-314. DOI: 10.1302/2046-3758.65.BJR-2016-0192.R1.
PMID- 28515062
TI - Changes in total energy intake and macronutrient composition after bariatric
surgery predict long-term weight outcome: findings from the Swedish Obese
Subjects (SOS) study.
AB - Background: Approximately 20-30% of obese patients do not achieve successful
weight outcomes after bariatric surgery.Objective: We examined whether short-term
changes (<=0.5 y postsurgery) in energy intake and macronutrient composition
after bariatric surgery could predict 10-y weight change.Design: Participants
were recruited from the Swedish Obese Subjects (SOS) study, which was a matched
(nonrandomized) prospective trial that compared bariatric surgery with usual care
for obese patients. A total of 2010 patients who underwent bariatric surgery were
included in the study. Physical examinations (e.g., weight) and questionnaires
(e.g., dietary questionnaire) were completed before and 0.5, 1, 2, 3, 4, 6, 8,
and 10 y after surgery. For the main analytic strategy, a linear mixed model was
implemented, which included repeated measures with a random intercept and an
unstructured covariance matrix.Results: Short-term changes in energy intake (P <
0.001) and in relative proportions of energy from carbohydrates (P < 0.001), fat
(P < 0.001), and protein (P < 0.05) were associated with 10-y weight change after
bariatric surgery. At the 10-y follow-up, men and women with the largest
reductions in energy intake had lost 7.3% and 3.9% more weight, respectively,
compared with that of subjects with the smallest intake reductions (P < 0.001).
Greater weight loss was achieved in men and women who favored protein and
carbohydrates over fat and in subjects who favored protein over carbohydrates
than in individuals who favored the opposite changes in macronutrient composition
(P < 0.05).Conclusions: The level of energy restriction that is achieved at 0.5 y
after bariatric surgery predicts long-term weight loss. Weight loss is also
associated with a changing dietary macronutrient composition. This trial was
registered at clinicaltrials.gov as NCT01479452.
PMID- 28515063
TI - Learning to like vegetables during breastfeeding: a randomized clinical trial of
lactating mothers and infants.
AB - Background: What lactating mothers eat flavors breast milk and, in turn, modifies
their infants' acceptance of similarly flavored foods.Objective: We sought to
determine the effects of the timing and duration of eating a variety of
vegetables during breastfeeding on the liking of vegetables in both members of
the dyad.Design: We conducted a randomized controlled study of 97 mother-infant
dyads. Lactating mothers drank vegetable, beet, celery, and carrot juices for 1
mo beginning at 0.5, 1.5, or 2.5 mo postpartum or for 3 mo beginning at 0.5 mo
postpartum. The control group drank equal volumes of water and avoided drinking
the juices. Mothers rated the tastes of the juices and self-reported dietary
intakes at each monthly visit (0.5-4.5 mo). After weaning, when 7.9 mo of age,
infants' acceptance of plain, carrot-flavor (exposed flavor), and broccoli-flavor
(nonexposed flavor) cereals was assessed on separate days.Results: The timing of
exposure affected the acceptance of the carrot flavor that did not generalize to
the novel broccoli flavor. A relatively brief experience (1 mo) with vegetable
flavors in mothers' milk, starting at 0.5 mo postpartum, was sufficient to shift
the hedonic tone, which resulted in a faster rate of eating carrot-flavored
cereal than that in infants who were exposed during subsequent months or not at
all. One month of exposure had a greater effect than 3 mo of exposure or no
exposure. Regardless of when exposure occurred, infants were less likely to
display facial expressions of distaste initially when eating the carrot cereal.
Over time, mothers liked the tastes of carrot, beet, and celery juices more, but
no changes in dietary intake of vegetables were observed.Conclusions: Early life
may be an optimum time for both infants and their mothers to learn to like the
taste of healthy foods. More research is needed to facilitate the liking and
eating of these foods by mothers, which will, in turn, increase the likelihood of
their feeding these foods to their children. This trial was registered at
clinicaltrials.gov as NCT01667549.
PMID- 28515065
TI - Neonatal vitamin D status from archived dried blood spots and future risk of
fractures in childhood: results from the D-tect study, a population-based case
cohort study.
AB - Background: Whether antenatal and neonatal vitamin D status have clinical
relevance in fracture prevention has not been examined extensively, although
observational studies indicate that fetal life may be a sensitive period in
relation to bone growth and mineralization during childhood.Objective: We
examined whether 25-hydroxyvitamin D3 [25(OH)D3] concentrations in stored
neonatal dried blood spot (DBS) samples are associated with pediatric fracture
risk. We hypothesized that in particular, low neonatal vitamin D status may be a
risk factor for fracture incidence among children.Design: In a register-based
case-cohort study design, the case group was composed of 1039 individuals who
were randomly selected from a total of 82,154 individuals who were born during
1989-1999 and admitted to a Danish hospital with a fracture of the forearm,
wrist, scaphoid bone, clavicle, or ankle at age 6-13 y. The subcohort was
composed of 1600 individuals randomly selected from all Danish children born
during 1989-1999. The neonatal 25(OH)D3 concentrations in DBS samples were
assessed by using highly sensitive chromatography-tandem mass
spectrometry.Results: The mean +/- SD 25(OH)D3 concentration for all subjects was
27.7 +/- 18.9 nmol/L [median (IQR): 23.5 nmol/L (13.3, 37.3 nmol/L)] and showed
significant monthly variation (P < 0.0001) with the highest values in July and
August. Individuals in the middle quintile of neonatal 25(OH)D3 had lower odds of
sustaining a fracture than did those in the lowest quintile (adjusted OR: 0.75;
95% CI: 0.58, 0.96), but a global test did not show any significant overall
association (adjusted P = 0.13).Conclusions: This study suggested that neonatal
vitamin D status does not influence subsequent fracture risk in childhood. This
is in accordance with studies that report no association between antenatal
maternal vitamin D status and childhood fractures. Further studies are needed to
examine fracture risk in relation to prenatal vitamin D status in a randomized
controlled setting.
PMID- 28515066
TI - Estimating salt intake in humans: not so easy!
PMID- 28515064
TI - Genetics of serum carotenoid concentrations and their correlation with obesity
related traits in Mexican American children.
AB - Background: Dietary intake of phytonutrients present in fruits and vegetables,
such as carotenoids, is associated with a lower risk of obesity and related
traits, but the impact of genetic variation on these associations is poorly
understood, especially in children.Objective: We estimated common genetic
influences on serum carotenoid concentrations and obesity-related traits in
Mexican American (MA) children.Design: Obesity-related data were obtained from
670 nondiabetic MA children, aged 6-17 y. Serum alpha- and beta-carotenoid
concentrations were measured in ~570 (alpha-carotene in 565 and beta-carotene in
572) of these children with the use of an ultraperformance liquid chromatography
photodiode array. We determined heritabilities for both carotenoids and examined
their genetic relation with 10 obesity-related traits [body mass index (BMI),
waist circumference (WC), high-density lipoprotein (HDL) cholesterol,
triglycerides, fat mass (FM), systolic and diastolic blood pressure, fasting
insulin and glucose, and homeostasis model assessment of insulin resistance] by
using family data and a variance components approach. For these analyses,
carotenoid values were inverse normalized, and all traits were adjusted for
significant covariate effects of age and sex.Results: Carotenoid concentrations
were highly heritable and significant [alpha-carotene: heritability (h2) = 0.81,
P = 6.7 * 10-11; beta-carotene: h2 = 0.90, P = 3.5 * 10-15]. After adjusting for
multiple comparisons, we found significant (P <= 0.05) negative phenotypic
correlations between carotenoid concentrations and the following traits: BMI, WC,
FM, and triglycerides (range: alpha-carotene = -0.19 to -0.12; beta-carotene =
0.24 to -0.13) and positive correlations with HDL cholesterol (alpha-carotene =
0.17; beta-carotene = 0.24). However, when the phenotypic correlations were
partitioned into genetic and environmental correlations, we found marginally
significant (P = 0.051) genetic correlations only between beta-carotene and BMI (
0.27), WC (-0.30), and HDL cholesterol (0.31) after accounting for multiple
comparisons. None of the environmental correlations were significant.Conclusions:
The findings from this study suggest that the serum carotenoid concentrations
were under strong additive genetic influences based on variance components
analyses, and that the common genetic factors may influence beta-carotene and
obesity and lipid traits in MA children.
PMID- 28515067
TI - Relative contribution of alpha-carotene to postprandial vitamin A concentrations
in healthy humans after carrot consumption.
AB - Background: Asymmetric alpha-carotene, a provitamin A carotenoid, is cleaved to
produce retinol (vitamin A) and alpha-retinol (with negligible vitamin A
activity). The vitamin A activity of alpha-carotene-containing foods is likely
overestimated because traditional analytic methods do not separate alpha-retinol
derivatives from active retinol.Objective: This study aimed to accurately
characterize intestinal alpha-carotene cleavage and its relative contribution to
postprandial vitamin A in humans after consumption of raw carrots.Design: Healthy
adults (n = 12) consumed a meal containing 300 g raw carrot (providing 27.3 mg
beta-carotene and 18.7 mg alpha-carotene). Triglyceride-rich lipoprotein
fractions of plasma were isolated and extracted, and alpha-retinyl palmitate
(alphaRP) and retinyl palmitate were measured over 12 h postprandially via high
performance liquid chromatography-tandem mass spectrometry. The complete profile
of all alpha-retinyl esters and retinyl esters was measured at 6 h, and total
absorption of alpha- and beta-carotene was calculated.Results: alphaRP was
identified and quantified in every subject. No difference in preference for
absorption of beta- over alpha-carotene was observed (adjusting for dose, 28%
higher, P = 0.103). After absorption, beta-carotene trended toward preferential
cleavage compared with alpha-carotene (22% higher, P = 0.084). A large range of
provitamin A carotenoid conversion efficiencies was observed, with alpha-carotene
contributing 12-35% of newly converted vitamin A (predicted contribution =
25.5%). In all subjects, a majority of alpha-retinol was esterified to palmitic
acid (as compared with other fatty acids).Conclusions: alpha-Retinol is
esterified in the enterocyte and transported in the blood analogous to retinol.
The percentage of absorption of alpha-carotene from raw carrots was not
significantly different from beta-carotene when adjusting for dose, although a
trend toward higher cleavage of beta-carotene was observed. The results
demonstrate large interindividual variability in alpha-carotene conversion. The
contribution of newly absorbed alpha-carotene to postprandial vitamin A should
not be estimated but should be measured directly to accurately assess the vitamin
A capacity of alpha-carotene-containing foods. This trial was registered at
clinicaltrials.gov as NCT01432210.
PMID- 28515068
TI - Low-fat dietary pattern and cardiovascular disease: results from the Women's
Health Initiative randomized controlled trial.
AB - Background: The influence of a low-fat dietary pattern on the cardiovascular
health of postmenopausal women continues to be of public health
interest.Objective: This report evaluates low-fat dietary pattern influences on
cardiovascular disease (CVD) incidence and mortality during the intervention and
postintervention phases of the Women's Health Initiative Dietary Modification
Trial.Design: Participants comprised 48,835 postmenopausal women aged 50-79 y;
40% were randomly assigned to a low-fat dietary pattern intervention (target of
20% of energy from fat), and 60% were randomly assigned to a usual diet
comparison group. The 8.3-y intervention period ended in March 2005, after which
>80% of surviving participants consented to additional active follow-up through
September 2010; all participants were followed for mortality through 2013. Breast
and colorectal cancer were the primary trial outcomes, and coronary heart disease
(CHD) and overall CVD were additional designated outcomes.Results: Incidence
rates for CHD and total CVD did not differ between the intervention and
comparison groups in either the intervention or postintervention period. However,
CHD HRs comparing these groups varied strongly with baseline CVD and hypertension
status. Participants without prior CVD had an intervention period CHD HR of 0.70
(95% CI: 0.56, 0.87) or 1.04 (95% CI: 0.90, 1.19) if they were normotensive or
hypertensive, respectively (P-interaction = 0.003). The CHD benefit among healthy
normotensive women was partially offset by an increase in ischemic stroke risk.
Corresponding HRs in the postintervention period were close to null. Participants
with CVD at baseline (3.4%) had CHD HRs of 1.47 (95% CI: 1.12, 1.93) and 1.61
(95% CI: 1.02, 2.55) in the intervention and postintervention periods,
respectively. However, various lines of evidence suggest that results in women
with CVD or hypertension at baseline are confounded by postrandomization use of
cholesterol-lowering medications.Conclusions: CVD risk in postmenopausal women
appears to be sensitive to a change to a low-fat dietary pattern and, among
healthy women, includes both CHD benefit and stroke risk. This trial was
registered at clinicaltrials.gov as NCT00000611.
PMID- 28515069
TI - Mendelian randomization shows sex-specific associations between long-chain PUFA
related genotypes and cognitive performance in Danish schoolchildren.
AB - Background: Dietary and endogenously formed long-chain polyunsaturated fatty
acids (LCPUFAs) are hypothesized to improve cognitive development, but results
are inconclusive, with suggestions of sex specificity. One study suggested that
single-nucleotide polymorphisms (SNPs) rs1535 and rs174448 in the fatty acid
desaturase (FADS) gene cluster have opposite effects on erythrocyte LCPUFAs at 9
mo.Objective: To explore whether SNPs in FADS and elongase (ELOVL) genes were
associated with school performance in a sex-specific manner, we performed a
Mendelian randomization study using data from the Optimal well-being, development
and health for Danish children through a healthy New Nordic Diet (OPUS) School
Meal Study with 765 Danish schoolchildren 8-11 y old.Design: Associations between
selected FADS1/2 SNPs (rs1535, rs174448, and rs174468) and ELOVL5 rs2397142,
whole-blood fatty acid composition, and performance in the d2 Test of Attention
and a reading test were analyzed in multiple regression models including all
SNPs, SNP-sex interactions, and covariates related to testing
conditions.Results:FADS, rs1535 minor allele carriage associated with lower whole
blood arachidonic acid (P <= 0.002), and minor alleles of rs174448 tended to
associate with lower docosahexaenoic acid (DHA) (P = 0.052). We identified sex
interactions in 50% of the SNP performance sets. Sex-dependent associations were
observed for rs174448 and rs1535 on the d2 Test of Attention outcomes (P < 0.03)
and for the associations between reading scores and rs174448 and rs2397142 (P <
0.01). All of the sex-specific analyses showed associations in opposite
directions in girls and boys. The minor allele carriage of rs174448 was
associated with lower d2 Test of Attention performance (P < 0.02) and reading
scores (P < 0.001) in boys but with better reading scores in girls (P <= 0.002).
The associations were consistently the opposite for rs1535 minor allele carriage
(P < 0.05). Associations with rs2397142 also appeared to be opposite of those of
rs174448, but only for reading and not significant after adjustment for parental
educational level and whole-blood DHA.Conclusions: This study showed associations
between rs1535 minor allele homozygosity and rs174448 major allele carriage and
improved performance in 8- to 11-y-old boys but not in girls, thereby
counteracting existing sex differences. This may be a consequence of increased
endogenous DHA synthesis in infancy but not at school-age. This trial was
registered at clinicaltrials.gov as NCT01457794.
PMID- 28515070
TI - Even mealtime distribution of protein intake is associated with greater muscle
strength, but not with 3-y physical function decline, in free-living older
adults: the Quebec longitudinal study on Nutrition as a Determinant of Successful
Aging (NuAge study).
AB - Background: Functional status declines with aging, thus impeding autonomy.
Recently, a more even mealtime distribution of dietary protein was positively
associated with muscle mass, but the relation of this distribution to physical
performance remains unknown.Objective: We examined the relation between mealtime
protein-intake distribution and physical performance and its 3-y decline in
community-dwelling older adults.Design: Three-year follow-up data from 827 men
and 914 women (67-84 y) in the longitudinal study on nutrition and aging [Quebec
longitudinal study on Nutrition as a Determinant of Successful Aging (NuAge
study); Quebec, Canada] were analyzed. Physical performance, which was measured
yearly, was grouped into the following 2 functional composite scores: muscle
strength (handgrip, arm, and leg) and mobility (timed-up-and-go, chair stand, and
walking speed). Dietary data were collected in 2 sets of three 24-h food recalls
at baseline and year 2. The individual mealtime protein distribution was
calculated as the CV (i.e., SD divided by the mean) of grams of protein per meal.
A mixed model analysis was used to examine trajectories of muscle strength and
mobility across time by sex as conditioned by the protein distribution and
adjusted for potential covariates.Results: Physical performance deteriorated over
3 y with muscle strength declining more than the mobility score in men (-1.51 +/-
1.68 compared with -0.66 +/- 2.81) and women (-1.35 +/- 1.77 compared with -0.78
+/- 2.63) (means +/- SD, P < 0.001). More-evenly distributed protein intake,
independent of the total quantity, was associated with a higher muscle-strength
score in both sexes throughout follow-up. It was also associated with a greater
mobility score, but only in men and only before adjustment for covariates.
Strength and mobility rates of decline were not affected by protein-intake
distribution in either sex.Conclusions: In addition to the previously observed
association with lean mass, an even distribution of daily protein intake across
meals is independently associated with greater muscle strength, but not with the
mobility score, in older adults. A longer-term investigation of the role of
protein intake and its distribution on physical performance is warranted, as are
intervention studies, to support future recommendations.
PMID- 28515071
TI - Challenges in defining the role of dietary protein in bone health.
PMID- 28515073
TI - Monsters and angels.
PMID- 28515074
TI - Immune checkpoints on innate lymphoid cells.
AB - In this issue of JEM, Taylor et al. (https://doi.org/10.1084/jem.20161653)
describe PD-1 as a critical negative regulator of group 2 innate lymphoid cells
(ILC-2s). PD-1 intrinsically controls proliferation and cytokine production of
both mouse and human ILC-2s. PD-1 signaling inhibits STAT5 phosphorylation and
the removal of this brake by knocking down PD-1 expression or by using anti-PD-1
blocking antibodies, translated in vivo into better clearance of helminth worm
infection in mice.
PMID- 28515076
TI - Vertically transmitted symbionts as mechanisms of transgenerational effects.
AB - PREMISE OF THE STUDY: A transgenerational effect occurs when a biotic or abiotic
environmental factor acts on a parental individual and thereby affects the
phenotype of progeny. Due to the importance of transgenerational effects for
understanding plant ecology and evolution, their underlying mechanisms are of
general interest. Here, we introduce the concept that inherited symbiotic
microorganisms could act as mechanisms of transgenerational effects in plants.
METHODS: We define the criteria required to demonstrate that transgenerational
effects are microbially mediated and review evidence from the well-studied,
vertically transmitted plant-fungal symbiosis (grass-Epichloe spp.) in support of
such effects. We also propose a basic experimental design to test for the
presence of adaptive transgenerational effects mediated by plant symbionts. KEY
RESULTS: An increasingly large body of literature shows that vertically
transmitted microorganisms are common in plants, with potential to affect the
phenotypes and fitness of progeny. Transgenerational effects could occur via
parental modification of symbiont presence/absence, symbiont load, symbiont
products, symbiont genotype or species composition, or symbiont priming. Several
of these mechanisms appear likely in the grass-Epichloe endophytic symbiosis, as
there is variation in the proportion of the progeny that carries the fungus, as
well as variation in concentrations of mycelia and secondary compounds (alkaloids
and osmolytes) in the seed. CONCLUSIONS: Symbiont-mediated transgenerational
effects could be common in plants and could play large roles in plant adaptation
to changing environments, but definitive tests are needed. We hope our
contribution will spark new lines of research on the transgenerational effects of
vertically transmitted symbionts in plants.
PMID- 28515075
TI - pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial
brain invasion.
AB - Streptococcus pneumoniae is the main cause of bacterial meningitis, a life
threating disease with a high case fatality rate despite treatment with
antibiotics. Pneumococci cause meningitis by invading the blood and penetrating
the blood-brain barrier (BBB). Using stimulated emission depletion (STED) super
resolution microscopy of brain biopsies from patients who died of pneumococcal
meningitis, we observe that pneumococci colocalize with the two BBB endothelial
receptors: polymeric immunoglobulin receptor (pIgR) and platelet endothelial cell
adhesion molecule (PECAM-1). We show that the major adhesin of the pneumococcal
pilus-1, RrgA, binds both receptors, whereas the choline binding protein PspC
binds, but to a lower extent, only pIgR. Using a bacteremia-derived meningitis
model and mutant mice, as well as antibodies against the two receptors, we
prevent pneumococcal entry into the brain and meningitis development. By adding
antibodies to antibiotic (ceftriaxone)-treated mice, we further reduce the
bacterial burden in the brain. Our data suggest that inhibition of pIgR and PECAM
1 has the potential to prevent pneumococcal meningitis.
PMID- 28515072
TI - omega-3 and omega-6 long-chain PUFAs and their enzymatic metabolites in
neovascular eye diseases.
AB - Neovascular eye diseases, including retinopathy of prematurity, diabetic
retinopathy, and age-related macular degeneration, threaten the visual health of
children and adults. Current treatment options, including anti-vascular
endothelial growth factor therapy and laser retinal photocoagulation, have
limitations and are associated with adverse effects; therefore, the
identification of additional therapies is highly desirable. Both clinical and
experimental studies show that dietary omega-3 (n-3) long-chain polyunsaturated
fatty acids (LC-PUFAs) reduce retinal and choroidal angiogenesis. The omega-3 LC
PUFA metabolites from 2 groups of enzymes, cyclooxygenases and lipoxygenases,
inhibit [and the omega-6 (n-6) LC-PUFA metabolites promote] inflammation and
angiogenesis. However, both of the omega-3 and the omega-6 lipid products of
cytochrome P450 oxidase 2C promote neovascularization in both the retina and
choroid, which suggests that inhibition of this pathway might be beneficial. This
review summarizes our current understanding of the roles of omega-3 and omega-6
LC-PUFAs and their enzymatic metabolites in neovascular eye diseases.
PMID- 28515077
TI - Toward principles of historical ecology.
PMID- 28515078
TI - Shifting Quaternary migration patterns in the Bahamian archipelago: Evidence from
the Zamia pumila complex at the northern limits of the Caribbean island
biodiversity hotspot.
AB - PREMISE OF THE STUDY: The Bahamas archipelago is formed by young, tectonically
stable carbonate banks that harbor direct geological evidence of global ice
volume changes. We sought to detect signatures of major changes on gene flow
patterns and reconstruct the phylogeographic history of the monophyletic Zamia
pumila complex across the Bahamas. METHODS: Nuclear molecular markers with both
high and low mutation rates were used to capture two different time scale
signatures and test several gene flow and demographic hypotheses. KEY RESULTS:
Single-copy nuclear genes unveiled apparent ancestral admixture on Andros,
suggesting a significant role of this island as main hub of diversity of the
archipelago. We detected demographic and spatial expansion of the Zamia pumila
complex on both paleo-provinces around the Piacenzian (Pliocene)/Gelasian
(Pleistocene). Populations evidenced signatures of different migration models
that have occurred at two different times. Populations on Long Island (Z.
lucayana) may either represent a secondary colonization of the Bahamas by Zamia
or a rapid and early-divergence event of at least one population on the Bahamas.
CONCLUSIONS: Despite changes in migration patterns with global climate, expected
heterozygosity with both marker systems remains within the range reported for
cycads, but with significant levels of increased inbreeding detected by the
microsatellites. This finding is likely associated with reduced gene flow between
and within paleo-provinces, accompanied by genetic drift, as rising seas enforced
isolation. Our study highlights the importance of the maintenance of the
predominant direction of genetic exchange and the role of overseas dispersion
among the islands during climate oscillations.
PMID- 28515079
TI - Impact of acetaminophen consumption and resistance exercise on extracellular
matrix gene expression in human skeletal muscle.
AB - Acetaminophen (APAP) given during chronic exercise reduces skeletal muscle
collagen and cross-linking in rats. We propose that the effect of APAP on muscle
extracellular matrix (ECM) may, in part, be mediated by dysregulation of the
balance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs
(TIMPs). The purpose of this study was to evaluate the impact of APAP consumption
during acute resistance exercise (RE) on several regulators of the ECM in human
skeletal muscle. In a double-blinded, placebo-controlled, randomized crossover
design, recreationally active men (n = 8, 25 +/- 2 yr) performed two trials of
knee extension. Placebo (PLA) or APAP (1,000 mg/6 h) was given for 24 h before
and immediately following RE. Vastus lateralis biopsies were taken at baseline
and 1 and 3 h post-RE. Quantitative RT-PCR was used to determine differences in
mRNA expression. MMP-2, type I collagen, and type III collagen mRNA expression
was not altered by exercise or APAP (P > 0.05). When compared with PLA, TIMP-1
expression was lower at 1 h post-RE during APAP conditions but greater than PLA
at 3 h post-RE (P < 0.05). MMP-9 expression and protein levels were elevated at 3
h post-RE independent of treatment (P < 0.05). Lysyl oxidase expression was
greater at 3 h post-RE during APAP consumption (P < 0.05) compared with PLA. MMP
2 and TIMP-1 protein was not altered by RE or APAP (P > 0.05). Phosphorylation of
ERK1/2 and p38-MAPK increased (P < 0.05) with RE but was not influenced by APAP.
Our findings do not support our hypothesis and suggest that short-term APAP
consumption before RE has a small impact on the measured ECM molecules in human
skeletal muscle following acute RE.
PMID- 28515080
TI - Effect of resistance exercise under conditions of reduced blood insulin on
AMPKalpha Ser485/491 inhibitory phosphorylation and AMPK pathway activation.
AB - Insulin stimulates skeletal muscle glucose uptake via activation of the protein
kinase B/Akt (Akt) pathway. Recent studies suggest that insulin downregulates AMP
activated protein kinase (AMPK) activity via Ser485/491 phosphorylation of the
AMPK alpha-subunit. Thus lower blood insulin concentrations may induce AMPK
signal activation. Acute exercise is one method to stimulate AMPK activation;
however, no study has examined the relationship between blood insulin levels and
acute resistance exercise-induced AMPK pathway activation. Based on previous
findings, we hypothesized that the acute resistance exercise-induced AMPK pathway
activation would be augmented by disruptions in insulin secretion through a
decrease in AMPKalpha Ser485/491 inhibitory phosphorylation. To test the
hypothesis, 10-wk-old male Sprague-Dawley rats were administered the toxin
streptozotocin (STZ; 55 mg/kg) to destroy the insulin secreting beta-cells. Three
days postinjection, the right gastrocnemius muscle from STZ and control rats was
subjected to resistance exercise by percutaneous electrical stimulation. Animals
were killed 0, 1, or 3 h later; activation of the Akt/AMPK and downstream
pathways in the muscle tissue was analyzed by Western blotting and real-time PCR.
Notably, STZ rats showed a significant decrease in basal Akt and AMPKalpha
Ser485/491 phosphorylation, but substantial exercise-induced increases in both
AMPKalpha Thr172 and acetyl-CoA carboxylase (ACC) Ser79 phosphorylation were
observed. Although no significant impact on resistance exercise-induced Akt
pathway activation or glucose uptake was found, resistance exercise-induced
peroxisome proliferator-activated receptor (PPAR)-gamma coactivator-1 alpha (PGC
1alpha) gene expression was augmented by STZ treatment. Collectively, these data
suggest that circulating insulin levels may regulate acute resistance exercise
induced AMPK pathway activation and AMPK-dependent gene expression relating to
basal AMPKalpha Ser485/491 phosphorylation.
PMID- 28515082
TI - Parkin-independent mitophagy-FKBP8 takes the stage.
AB - Although the Parkin/PINK1 pathway has received considerable attention in recent
years as a key regulator of mitophagy in mammals, it is important to recognize
that multiple mitophagy receptors like BNIP3, NIX, and FUNDC1 exist that can
promote the selective clearance of mitochondria in the absence of Parkin. In this
issue, Bhujabal et al expand the repertoire of Parkin-independent mitophagy
receptors to include the anti-apoptotic protein, FKBP8. The authors demonstrate
that FKBP8 interacts preferentially with LC3A via its LIR motif to destroy
damaged mitochondria. During the process, FKBP8 escapes from the destruction
presumably to prevent apoptosis during mitophagy [1].
PMID- 28515081
TI - Flexible ammonia handling strategies using both cutaneous and branchial epithelia
in the highly ammonia-tolerant Pacific hagfish.
AB - Hagfish consume carrion, potentially exposing them to hypoxia, hypercapnia, and
high environmental ammonia (HEA). We investigated branchial and cutaneous ammonia
handling strategies by which Pacific hagfish (Eptatretus stoutii) tolerate and
recover from high ammonia loading. Hagfish were exposed to HEA (20 mmol/l) for 48
h to elevate plasma total ammonia (TAmm) levels before placement into divided
chambers for a 4-h recovery period in ammonia-free seawater where ammonia
excretion (JAmm) was measured independently in the anterior and posterior
compartments. Localized HEA exposures were also conducted by subjecting hagfish
to HEA in either the anterior or posterior compartments. During recovery, HEA
exposed animals increased JAmm in both compartments, with the posterior
compartment comprising ~20% of the total JAmm compared with ~11% in non-HEA
exposed fish. Plasma TAmm increased substantially when whole hagfish and the
posterior regions were exposed to HEA. Alternatively, plasma TAmm did not elevate
after anterior localized HEA exposure. JAmm was concentration dependent (0.05-5
mmol/l) across excised skin patches at up to eightfold greater rates than in skin
sections that were excised from HEA-exposed hagfish. Skin excised from more
posterior regions displayed greater JAmm than those from more anterior regions.
Immunohistochemistry with hagfish-specific anti-rhesus glycoprotein type c (alpha
hRhcg; ammonia transporter) antibody was characterized by staining on the basal
aspect of hagfish epidermis while Western blotting demonstrated greater
expression of Rhcg in more posterior skin sections. We conclude that cutaneous
Rhcg proteins are involved in cutaneous ammonia excretion by Pacific hagfish and
that this mechanism could be particularly important during feeding.
PMID- 28515083
TI - Self-healing capacity of deep-sea ecosystems affected by petroleum hydrocarbons:
Understanding microbial oil degradation at hydrocarbon seeps is key to
sustainable bioremediation protocols.
PMID- 28515084
TI - Novel diagnostic technologies for clinical and frontline use: Advanced
diagnostics based on molecular markers and analysis technologies has been
improving diagnosis across a wide range of diseases.
PMID- 28515086
TI - Multi-omics and Alzheimer's disease: a slower but surer path to an efficacious
therapy?
PMID- 28515085
TI - Regulation of ATP production: dependence on calcium concentration and respiratory
state.
AB - Nanomolar free calcium enhances oxidative phosphorylation. However, the effects
over a broad concentration range, at different respiratory states, or on specific
energy substrates are less clear. We examined the action of varying [Ca2+] over
respiratory states ranging 4 to 3 on skeletal muscle mitochondrial respiration,
potential, ATP production, and H2O2 production using ADP recycling to clamp
external [ADP]. Calcium at 450 nM enhanced respiration in mitochondria energized
by the complex I substrates, glutamate/malate (but not succinate), at [ADP] of 4
256 uM, but more substantially at intermediate respiratory states and not at all
at state 4. Using varied [Ca2+], we found that the stimulatory effects on
respiration and ATP production were most prominent at nanomolar concentrations,
but inhibitory at 10 uM or higher. ATP production decreased more than respiration
at 10 uM calcium. However, potential continued to increase up to 10 uM;
suggesting a calcium-induced inability to utilize potential for phosphorylation
independent of opening of the mitochondrial permeability transition pore (MTP).
This effect of 10 uM calcium was confirmed by direct determination of ATP
production over a range of potential created by differing substrate
concentrations. Consistent with past reports, nanomolar [Ca2+] had a stimulatory
effect on utilization of potential for phosphorylation. Increasing [Ca2+] was
positively and continuously associated with H2O2 production. In summary, the
stimulatory effect of calcium on mitochondrial function is substrate dependent
and most prominent over intermediate respiratory states. Calcium stimulates or
inhibits utilization of potential for phosphorylation dependent on concentration
with inhibition at higher concentration independent of MTP opening.
PMID- 28515087
TI - FXYD5 (dysadherin) may mediate metastatic progression through regulation of the
beta-Na+-K+-ATPase subunit in the 4T1 mouse breast cancer model.
AB - FXYD5 is a Na+-K+-ATPase regulator, expressed in a variety of normal epithelia.
In parallel, it has been found to be associated with several types of cancer and
effect lethal outcome by promoting metastasis. However, the molecular mechanism
underlying FXYD5 mediated invasion has not yet been identified. In this study,
using in vivo 4T1 murine breast cancer model, we found that FXYD5-specific shRNA
significantly inhibited lung cancer metastasis, without having a substantial
effect on primary tumor growth. Our study reveals that FXYD5 participates in
multiple stages of metastatic development and exhibits more than one mode of E
cadherin regulation. We provide the first evidence that FXYD5-related
morphological changes are mediated through its interaction with Na+-K+-ATPase.
Experiments in cultured 4T1 cells have indicated that FXYD5 expression may
downregulate the beta1 isoform of the pump. This behavior could have implications
on both transcellular interactions and intracellular events. Further studies
suggest that differential localization of the adaptor protein Annexin A2 in FXYD5
expressing cells may correlate with matrix metalloproteinase 9 secretion and
adhesion changes in 4T1 wild-type cells.
PMID- 28515088
TI - Loss of NHERF-1 expression prevents dopamine-mediated Na-K-ATPase regulation in
renal proximal tubule cells from rat models of hypertension: aged F344 rats and
spontaneously hypertensive rats.
AB - Dopamine decreases Na-K-ATPase (NKA) activity by PKC-dependent phosphorylation
and endocytosis of the NKA alpha1. Dopamine-mediated regulation of NKA is
impaired in aging and some forms of hypertension. Using opossum (OK) proximal
tubule cells (PTCs), we demonstrated that sodium-hydrogen exchanger regulatory
factor-1 (NHERF-1) associates with NKA alpha1 and dopamine-1 receptor (D1R). This
association is required for the dopamine-mediated regulation of NKA. In OK cells,
dopamine decreases NHERF-1 association with NKA alpha1 but increases its
association with D1R. However, it is not known whether NHERF-1 plays a role in
dopamine-mediated NKA regulation in animal models of hypertension. We
hypothesized that defective dopamine-mediated regulation of NKA results from the
decrease in NHERF-1 expression in rat renal PTCs isolated from animal models of
hypertension [spontaneously hypertensive rats (SHRs) and aged F344 rats]. To test
this hypothesis, we isolated and cultured renal PTCs from 22-mo-old F344 rats and
their controls, normotensive 4-mo-old F344 rats, and SHRs and their controls,
normotensive Wistar-Kyoto (WKY) rats. The results demonstrate that in both
hypertensive models (SHR and aged F344), NHERF-1 expression, dopamine-mediated
phosphorylation of NKA, and ouabain-inhibitable K+ transport are reduced.
Transfection of NHERF-1 into PTCs from aged F344 and SHRs restored dopamine
mediated inhibition of NKA. These results suggest that decreased renal NHERF-1
expression contributes to the impaired dopamine-mediated inhibition of NKA in
PTCs from animal models of hypertension.
PMID- 28515090
TI - NF-kappaB p50 (nfkb1) contributes to pathogenesis in the EMU-TCL1 mouse model of
chronic lymphocytic leukemia.
PMID- 28515089
TI - The NH2 terminus regulates voltage-dependent gating of CALHM ion channels.
AB - Calcium homeostasis modulator protein-1 (CALHM1) and its Caenorhabditis elegans
(ce) homolog, CLHM-1, belong to a new family of physiologically important ion
channels that are regulated by voltage and extracellular Ca2+ (Ca2+o) but lack a
canonical voltage-sensing domain. Consequently, the intrinsic voltage-dependent
gating mechanisms for CALHM channels are unknown. Here, we performed voltage
clamp experiments on ceCLHM-1 chimeric, deletion, insertion, and point mutants to
assess the role of the NH2 terminus (NT) in CALHM channel gating. Analyses of
chimeric channels in which the ceCLHM-1 and human (h)CALHM1 NH2 termini were
interchanged showed that the hCALHM1 NT destabilized channel-closed states,
whereas the ceCLHM-1 NT had a stabilizing effect. In the absence of Ca2+o,
deletion of up to eight amino acids from the ceCLHM-1 NT caused a hyperpolarizing
shift in the conductance-voltage relationship with little effect on voltage
dependent slope. However, deletion of nine or more amino acids decreased voltage
dependence and induced a residual conductance at hyperpolarized voltages.
Insertion of amino acids into the NH2-terminal helix also decreased voltage
dependence but did not prevent channel closure. Mutation of ceCLHM-1 valine 9 and
glutamine 13 altered half-maximal activation and voltage dependence,
respectively, in 0 Ca2+ In 2 mM Ca2+o, ceCLHM-1 NH2-terminal deletion and point
mutant channels closed completely at hyperpolarized voltages with apparent
affinity for Ca2+o indistinguishable from wild-type ceCLHM-1, although the ceCLHM
1 valine 9 mutant exhibited an altered conductance-voltage relationship and
kinetics. We conclude that the NT plays critical roles modulating voltage
dependence and stabilizing the closed states of CALHM channels.
PMID- 28515092
TI - Human CD62Ldim neutrophils identified as a separate subset by proteome profiling
and in vivo pulse-chase labeling.
AB - During acute inflammation, 3 neutrophil subsets are found in the blood:
neutrophils with a conventional segmented nucleus, neutrophils with a banded
nucleus, and T-cell-suppressing CD62Ldim neutrophils with a high number of
nuclear lobes. In this study, we compared the in vivo kinetics and proteomes of
banded, mature, and hypersegmented neutrophils to determine whether these cell
types represent truly different neutrophil subsets or reflect changes induced by
lipopolysaccharide (LPS) activation. Using in vivo pulse-chase labeling of
neutrophil DNA with 6,6-2H2-glucose, we found that 2H-labeled banded neutrophils
appeared much earlier in blood than labeled CD62Ldim and segmented neutrophils,
which shared similar label kinetics. Comparison of the proteomes by cluster
analysis revealed that CD62Ldim neutrophils were clearly separate from
conventional segmented neutrophils despite having similar kinetics in peripheral
blood. Interestingly, the conventional segmented cells were more related at a
proteome level to banded cells despite a 2-day difference in maturation time. The
differences between CD62Ldim and mature neutrophils are unlikely to have been a
direct result of LPS-induced activation, because of the extremely low
transcriptional capacity of CD62Ldim neutrophils and the fact that neutrophils do
not directly respond to the low dose of LPS used in the study (2 ng/kg body
weight). Therefore, we propose CD62Ldim neutrophils are a truly separate
neutrophil subset that is recruited to the bloodstream in response to acute
inflammation. This trial was registered at www.clinicaltrials.gov as
#NCT01766414.
PMID- 28515091
TI - Angiotensin-converting enzyme enhances the oxidative response and bactericidal
activity of neutrophils.
AB - Angiotensin-converting enzyme (ACE) inhibitors are widely used to reduce blood
pressure. Here, we examined if an ACE is important for the antibacterial
effectiveness of neutrophils. ACE knockout mice or mice treated with an ACE
inhibitor were more susceptible to bacterial infection by methicillin-resistant
Staphylococcus aureus (MRSA). In contrast, mice overexpressing ACE in neutrophils
(NeuACE mice) have increased resistance to MRSA and better in vitro killing of
MRSA, Pseudomonas aeruginosa, and Klebsiella pneumoniae ACE overexpression
increased neutrophil production of reactive oxygen species (ROS) following MRSA
challenge, an effect independent of the angiotensin II AT1 receptor.
Specifically, as compared with wild-type (WT) mice, there was a marked increase
of superoxide generation (>twofold, P < .0005) in NeuACE neutrophils following
infection, whereas ACE knockout neutrophils decreased superoxide production.
Analysis of membrane p47-phox and p67-phox indicates that ACE increases reduced
NAD phosphate oxidase activity but does not increase expression of these
subunits. Increased ROS generation mediates the enhanced bacterial resistance of
NeuACE mice because the enhanced resistance is lost with DPI (an inhibitor of ROS
production by flavoenzymes) inhibition. NeuACE granulocytes also have increased
neutrophil extracellular trap formation and interleukin-1beta release in response
to MRSA. In a mouse model of chemotherapy-induced neutrophil depletion,
transfusion of ACE-overexpressing neutrophils was superior to WT neutrophils in
treating MRSA infection. These data indicate a previously unknown function of ACE
in neutrophil antibacterial defenses and suggest caution in the treatment of
certain individuals with ACE inhibitors. ACE overexpression in neutrophils may be
useful in boosting the immune response to antibiotic-resistant bacterial
infection.
PMID- 28515093
TI - Circulating soluble P-selectin must dimerize to promote inflammation and
coagulation in mice.
AB - Leukocyte adhesion to P-selectin on activated platelets and endothelial cells
induces shedding of the P-selectin ectodomain into the circulation. Plasma
soluble P-selectin (sP-selectin) is elevated threefold to fourfold in patients
with cardiovascular disease. Circulating sP-selectin is thought to trigger
signaling in leukocytes that directly contributes to inflammation and thrombosis.
However, sP-selectin likely circulates as a monomer, and in vitro studies suggest
that sP-selectin must dimerize to induce signaling in leukocytes. To address this
discrepancy, we expressed the entire ectodomain of mouse P-selectin as a monomer
(sP-selectin) or as a disulfide-linked dimer fused to the Fc portion of mouse
immunoglobulin G (sP-selectin-Fc). Dimeric sP-selectin-Fc, but not monomeric sP
selectin, triggered integrin-dependent adhesion of mouse leukocytes in vitro.
Antibody-induced oligomerization of sP-selectin or sP-selectin-Fc was required to
trigger formation of neutrophil extracellular traps. Injecting sP-selectin-Fc,
but not sP-selectin, into mice augmented integrin-dependent adhesion of
neutrophils in venules, generated tissue factor-bearing microparticles, shortened
plasma-clotting times, and increased thrombus frequency in the inferior vena
cava. Furthermore, transgenic mice that overexpressed monomeric sP-selectin did
not exhibit increased inflammation or thrombosis. We conclude that elevated
plasma sP-selectin is a consequence rather than a cause of cardiovascular
disease.
PMID- 28515096
TI - Leveraging Human Genetics to Understand the Relation of LDL Cholesterol with Type
2 Diabetes.
PMID- 28515095
TI - Prognostic index for chronic- and smoldering-type adult T-cell leukemia-lymphoma.
AB - Adult T-cell leukemia-lymphoma (ATL) has been divided into 4 clinical subtypes:
acute, lymphoma, chronic, and smoldering. The aim of this study is to develop a
novel prognostic index (PI) for chronic and smoldering ATL. We conducted a
nationwide retrospective survey on ATL patients, and 248 fully eligible
individuals were used in this analysis. In the univariate analysis, sex,
performance status, log10 (soluble interleukin-2 receptor [sIL-2R]), neutrophils
count, and lymphadenopathy showed values of P < .05 in training samples. A
multivariate analysis was performed on these factors, and only log10 (sIL-2R) was
identified as an independent prognostic factor in training samples. Using a
regression coefficient of this variable, a prognostic model was formulated to
identify different levels of risk: indolent ATL-PI (iATL-PI) = 1.51 * log10 (sIL
2R [U/mL]). The values calculated by iATL-PI were divided into 3 groups using a
quartile point. In the validation sample, median survival times (MSTs) were 1.6
years, 5.5 years, and not reached for patients in the high-, intermediate-, and
low-risk groups, respectively (P < .0001). To make the scoring system clinically
practicable, we simplified iATL-PI according to trichotomizing sIL-2R at 1000 and
6000 U/mL, using a quartile point. Patients with more than 6000 U/mL sIL-2R were
categorized into the high-risk group, less than and equal to 1000 U/mL into the
low-risk group, and the others into the intermediate-risk group, and MSTs were
1.6 years, not reached, and 5.5 years, respectively (P < .0001). iATL-PI has
potential as a novel tool for a risk-adapted therapeutic approach.
PMID- 28515097
TI - The Phoenix Rises: The Rebirth of Cancer Immunotherapy.
PMID- 28515094
TI - Inhibiting the osteocyte-specific protein sclerostin increases bone mass and
fracture resistance in multiple myeloma.
AB - Multiple myeloma (MM) is a plasma cell cancer that develops in the skeleton
causing profound bone destruction and fractures. The bone disease is mediated by
increased osteoclastic bone resorption and suppressed bone formation.
Bisphosphonates used for treatment inhibit bone resorption and prevent bone loss
but fail to influence bone formation and do not replace lost bone, so patients
continue to fracture. Stimulating bone formation to increase bone mass and
fracture resistance is a priority; however, targeting tumor-derived modulators of
bone formation has had limited success. Sclerostin is an osteocyte-specific Wnt
antagonist that inhibits bone formation. We hypothesized that inhibiting
sclerostin would prevent development of bone disease and increase resistance to
fracture in MM. Sclerostin was expressed in osteocytes from bones from naive and
myeloma-bearing mice. In contrast, sclerostin was not expressed by plasma cells
from 630 patients with myeloma or 54 myeloma cell lines. Mice injected with 5TGM1
eGFP, 5T2MM, or MM1.S myeloma cells demonstrated significant bone loss, which was
associated with a decrease in fracture resistance in the vertebrae. Treatment
with anti-sclerostin antibody increased osteoblast numbers and bone formation
rate but did not inhibit bone resorption or reduce tumor burden. Treatment with
anti-sclerostin antibody prevented myeloma-induced bone loss, reduced osteolytic
bone lesions, and increased fracture resistance. Treatment with anti-sclerostin
antibody and zoledronic acid combined increased bone mass and fracture resistance
when compared with treatment with zoledronic acid alone. This study defines a
therapeutic strategy superior to the current standard of care that will reduce
fractures for patients with MM.
PMID- 28515098
TI - Collagen Turnover Markers in Relation to Future Cardiovascular and
Noncardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis.
AB - BACKGROUND: Sustained remodeling of extracellular matrix can compromise organs
and tissues. Procollagen type III N-terminal propeptide (PIIINP) and collagen
type I carboxy-terminal telopeptide (ICTP) reflect collagen synthesis and
degradation. We studied their predictive value for future death and disease.
METHODS: A total of 3068 men and women in the Multi-Ethnic Study of
Atherosclerosis who were free of cardiovascular disease (CVD) and in generally
good health had a baseline blood sample taken for ICTP and PIIINP. Median follow
up was 13.0 years. Among 4 primary outcomes, CVD events (n = 697) were
adjudicated, death (n = 571) was by death certificate, and chronic inflammatory
related severe hospitalization and death (ChrIRD, n = 726) and total cancer (n =
327) were classified using International Classification of Diseases codes. We
used Poisson regression to study baseline ICTP and PIIINP relative to these
outcomes. RESULTS: Mean (SD) PIIINP was 5.47 (1.95) MUg/L and ICTP was 3.37
(1.70) MUg/L. PIIINP and ICTP were highly correlated with each other and with
estimated glomerular filtration rate (eGFR). Adjustment for age and eGFR
attenuated relative risks, remaining 20%-30% per SD of both PIIINP and ICTP in
prediction for total death and ChrIRD, and of PIIINP for cancer, with little
additional attenuation by adjusting for risk factors and inflammatory biomarkers.
CVD outcome was generally unrelated to PIIINP but became marginally inversely
related to ICTP in the most adjusted model. CONCLUSIONS: The collagen biomarkers
PIIINP and ICTP, in part through pathophysiologically parallel associations with
renal function, predicted ChrIRD and total death. Moreover, PIIINP predicted
future cancer. These collagen markers may help differentiate healthy from
unhealthy aging.
PMID- 28515101
TI - Laboratory Formulary: A Model for High-Value Evidence-Based Medicine.
PMID- 28515099
TI - Temporal Biomarker Profiling Reveals Longitudinal Changes in Risk of Death or
Myocardial Infarction in Non-ST-Segment Elevation Acute Coronary Syndrome.
AB - BACKGROUND: There are conflicting data on whether changes in N-terminal pro-B
type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hs
CRP) concentrations between time points (delta NT-proBNP and hs-CRP) are
associated with a change in prognosis. METHODS: We measured NT-proBNP and hs-CRP
at 3 time points in 1665 patients with non-ST-segment elevation acute coronary
syndrome (NSTEACS). Cox proportional hazards was applied to the delta between
temporal measurements to determine the continuous association with cardiovascular
events. Effect estimates for delta NT-proBNP and hs-CRP are presented per 40%
increase as the basic unit of temporal change. RESULTS: Median NT-proBNP was
370.0 (25th, 75th percentiles, 130.0, 996.0), 340.0 (135.0, 875.0), and 267.0
(111.0, 684.0) ng/L; and median hs-CRP was 4.6 (1.7, 13.1), 1.9 (0.8, 4.5), and
1.8 (0.8, 4.4) mg/L at baseline, 30 days, and 6 months, respectively. The deltas
between baseline and 6 months were the most prognostically informative. Every
+40% increase of delta NT-proBNP (baseline to 6 months) was associated with a 14%
greater risk of cardiovascular death (adjusted hazard ratio (HR) 1.14, 95% CI,
1.03-1.27) and with a 14% greater risk of all-cause death (adjusted HR 1.14, 95%
CI, 1.04-1.26), while every +40% increase of delta hs-CRP (baseline to 6 months)
was associated with a 9% greater risk of the composite end point (adjusted HR
1.09, 95% CI, 1.02-1.17) and a 10% greater risk of myocardial infarction
(adjusted HR 1.10, 95%, CI 1.00-1.20). CONCLUSIONS: Temporal changes in NT-proBNP
and hs-CRP are quantitatively associated with future cardiovascular events,
supporting their role in dynamic risk stratification of NSTEACS. CLINICAL TRIAL
REGISTRATION: ClinicalTrials.gov identifier NCT00699998.
PMID- 28515102
TI - American Liver Guidelines and Cutoffs for "Normal" ALT: A Potential for
Overdiagnosis.
PMID- 28515103
TI - Serial Measurement of Biomarkers after Acute Coronary Syndrome: Which One to
Choose?
PMID- 28515100
TI - Detection of Chromosomal Translocation in Hematologic Malignancies by a Novel DNA
Based Looped Ligation Assay (LOLA).
AB - BACKGROUND: Disease-defining chromosomal translocations are seen in various
neoplasms, especially in lymphomas and leukemias. Translocation detection at the
DNA level is often complicated by chromosomal breakpoints that are distributed
over very large regions. We have developed a ligation-based assay [the looped
ligation assay (LOLA)] to detect translocations from diseases with multiple
widely spaced breakpoint hot spots. METHODS: Oligonucleotide sets that probe
breakpoints of IGH-BCL2 (immunoglobulin heavy-apoptosis regulator) in follicular
lymphoma (FL), MYC-IGH (MYC proto-oncogene, bHLH transcription factor
immunoglobulin heavy) in Burkitt lymphoma (BL) and BCR-ABL1 (RhoGEF and GTPase
activating protein-ABL proto-oncogene 1, non-receptor tyrosine kinase) in chronic
myelogenous leukemia (CML) were designed. DNA from cell lines with these
translocations was mixed with oligonucleotides in a single-step ligation reaction
followed by PCR amplification. Detection was by capillary electrophoresis. We
also tested peripheral blood from 16 CML patients and frozen tissue from 17 FL
cases, and the results were compared to reverse transcription (RT)-PCR (CML) or
fluorescent in situ hybridization (FISH) and delta-PCR (FL). RESULTS: LOLA
produced signals of the expected sizes for the cell lines. Normal control DNA
yielded no signals. A dilution series yielded translocation-specific peaks at
dilutions as low as 1%. Signal intensity was log linear to the DNA concentration
(R2 = 0.94). Furthermore, we were able to detect a LOLA peak in DNA from 53.3% of
FL patients and 87.5% of CML patients. The concordance between LOLA, FISH, and
delta-PCR in FL was also excellent. CONCLUSIONS: Our results indicate that LOLA
is a simple method that is useful for DNA-based detection of translocations in
challenging situations, particularly where the breakpoints are not tightly
clustered. The assay also has the added benefit of permitting rapid mapping of
the breakpoints.
PMID- 28515104
TI - Pseudohypocalcemia in Cancer Patients: A Recommendation for the Postanalytical
Correction of Serum Calcium in Patients with Hypoalbuminemia.
PMID- 28515106
TI - Direct Comparison of 2 Rule-Out Strategies for Acute Myocardial Infarction: 2-h
Accelerated Diagnostic Protocol vs 2-h Algorithm.
AB - BACKGROUND: We compared 2 high-sensitivity cardiac troponin (hs-cTn)-based 2-h
strategies in patients presenting with suspected acute myocardial infarction
(AMI) to the emergency department (ED): the 2-h accelerated diagnostic protocol
(2h-ADP) combining hs-cTn, electrocardiogram, and a risk score, and the 2-h
algorithm exclusively based on hs-cTn concentrations and their absolute changes.
METHODS: Analyses were performed in 2 independent diagnostic cohorts [European
Advantageous Predictors of Acute Coronary Syndrome Evaluation (APACE) study,
Australian-New Zealand 2-h Accelerated Diagnostic Protocol to Assess patients
with chest Pain symptoms using contemporary Troponins as the only biomarker
(ADAPT) study] employing hs-cTnT (Elecsys) and hs-cTnI (Architect). The final
diagnosis was adjudicated by 2 independent cardiologists. RESULTS: AMI was the
final diagnosis in 16.5% (95% CI, 14.6%-18.6%) of the 1372 patients in APACE, and
12.6% (95% CI, 10.7%-14.7%) of 1153 patients in ADAPT. The negative predictive
value (NPV) and sensitivity for AMI were very high and comparable with both
strategies using either hs-cTnT or hs-cTnI in both cohorts (all statistical
comparisons nonsignificant). The percentage of patients triaged toward rule-out
was significantly lower with the 2h-ADP (36%-43%) vs the 2-h algorithm (55%-68%)
with both assays and in both cohorts (P < 0.001). The sensitivity of the 2h-ADP
was higher for 30-day major adverse cardiovascular events. CONCLUSIONS: Both
algorithms provided very high and comparable safety as quantified by the NPV and
sensitivity for AMI and major adverse cardiac events (MACE) at 30 days in
patients triaged toward rule-out, although sensitivity for MACE at 30 days was
lower with both algorithms in cohort 2. Although the 2-h algorithm was more
efficacious, not all patients ruled out for AMI by this algorithm were
appropriate candidates for early discharge. The 2h-ADP seems superior in the
selection of patients for early discharge from the ED. CLINICAL TRIAL
REGISTRATION: APACE: http://clinicaltrials.gov/show/NCT00470587ADAPT: Australia
New Zealand Clinical Trials Registry ACTRN12611001069943.
PMID- 28515107
TI - A Randomized Double-Blind Placebo-Controlled Trial of the Effect of Vitamin D3
Supplementation on Breast Density in Premenopausal Women.
AB - Background: This double-blind, placebo-controlled parallel group trial assessed
whether oral supplementation with 1,000, 2,000, or 3,000 IU/day vitamin D3 over
one year reduces percent mammographic breast density in premenopausal
women.Methods: The trial was conducted between October 2012 and June 2015, among
premenopausal female volunteers from Quebec City (Quebec, Canada). Women were
randomized with ratio 1:1:1:1 to one of four study arms (1,000, 2,000, or 3,000
IU/day vitamin D3 or placebo). The primary outcome was mean change in percent
mammographic breast density. Participants and research team were blinded to study
arm assignment.Results: Participants (n = 405) were randomized to receive 1,000
(n = 101), 2,000 (n = 104), or 3,000 IU/day (n = 101) vitamin D3, or a placebo (n
= 99). The primary analysis included 391 participants (96, 99, 100, and 96,
respectively). After the one-year intervention, mean +/- SE change in percent
breast density in the arms 1,000 IU/day (-5.5% +/- 0.5%) and 2,000 IU/day (-5.9%
+/- 0.5%) vitamin D3 was similar to that in the placebo arm (-5.7% +/- 0.5%) (P
values = 1.0). In the 3,000 IU/day vitamin D3 arm, percent breast density also
declined but slightly less (-3.8% +/- 0.5%) compared with placebo arm (P = 0.03).
Adherence to intervention was excellent (92.8%), and reporting of health problems
was comparable among study arms (P >= 0.95). All participants had normal serum
calcium.Conclusions: In premenopausal women, one-year supplementation with 1,000,
2,000, or 3,000 IU/day vitamin D3 resulted in a reduction of percent breast
density no greater than that seen with the placebo.Impact: At doses of 1,000
3,000 IU/day, vitamin D supplementation will not reduce breast cancer risk
through changes in breast density. Cancer Epidemiol Biomarkers Prev; 26(8); 1233
41. (c)2017 AACR.
PMID- 28515105
TI - Free-Circulating Methylated DNA in Blood for Diagnosis, Staging, Prognosis, and
Monitoring of Head and Neck Squamous Cell Carcinoma Patients: An Observational
Prospective Cohort Study.
AB - BACKGROUND: Circulating cell-free DNA methylation testing in blood has recently
received regulatory approval for screening of colorectal cancer. Its application
in other clinical settings, including staging, prognosis, prediction, and
recurrence monitoring is highly promising, and of particular interest in head and
neck squamous cell carcinomas (HNSCCs) that represent a heterogeneous group of
cancers with unsatisfactory treatment guidelines. METHODS: Short stature homeobox
2 (SHOX2) and septin 9 (SEPT9) DNA methylation in plasma from 649 prospectively
enrolled patients (training study: 284 HNSCC/122 control patients; testing study:
141 HNSCC/102 control patients) was quantified before treatment and
longitudinally during surveillance. RESULTS: In the training study, 59% of HNSCC
patients were methylation-positive at 96% specificity. Methylation levels
correlated with tumor and nodal category (P < 0.001). Initially increased
methylation levels were associated with a higher risk of death [SEPT9: hazard
ratio (HR) = 5.27, P = 0.001; SHOX2: HR = 2.32, P = 0.024]. Disease
recurrence/metastases were detected in 47% of patients up to 377 days earlier
compared to current clinical practice. The onset of second cancers was detected
up to 343 days earlier. In the testing study, sensitivity (52%), specificity
(95%), prediction of overall survival (SEPT9: HR = 2.78, P = 0.022; SHOX2: HR =
2.50, P = 0.026), and correlation with tumor and nodal category (P <0.001) were
successfully validated. CONCLUSIONS: Methylation testing in plasma is a powerful
diagnostic tool for molecular disease staging, risk stratification, and disease
monitoring. Patients with initially high biomarker levels might benefit from
intensified treatment and posttherapeutic surveillance. The early detection of a
recurrent/metastatic disease or a second malignancy could lead to an earlier
consecutive treatment, thereby improving patients' outcomes.
PMID- 28515109
TI - Updated Review of Prevalence of Major Risk Factors and Use of Screening Tests for
Cancer in the United States.
AB - Much of the suffering and death from cancer could be prevented by more systematic
efforts to reduce tobacco use and obesity, improve diet, and increase physical
activity and use of established vaccines and screening tests. Monitoring the
prevalence of cancer risk factors and preventive tests helps guide cancer
prevention and early detection efforts. We provide an updated review, using data
through 2015, of the prevalence of major risk factors, cancer screening, and
vaccination for U.S. adults and youth. Cigarette smoking among adults decreased
to 15.3% in 2015 but remains higher among lower socioeconomic persons (GED:
34.1%, graduate degree: 3.7%), with considerable state variation (Utah: 9.1%,
Kentucky: 26.0%). The prevalence of obesity among both adults (37.7%) and
adolescents (20.6%) remains high, particularly among black women (57.2%), and
ranges from 20.2% (Colorado) to 36.2% (Louisiana) among adults. Pap testing
remains the most commonly utilized cancer screening test (81.4%). While
colorectal cancer screening has increased, only 62.6% are up-to-date with
recommendations. Cancer screening is lowest among the uninsured and varies across
states. Despite some improvements, systematic efforts to further reduce the
suffering and death from cancer should be enhanced. Continued investment in
surveillance of cancer prevention and early detection metrics is also needed.
Cancer Epidemiol Biomarkers Prev; 26(8); 1192-208. (c)2017 AACR.
PMID- 28515108
TI - A Comparison of the Natural History of HPV Infection and Cervical Abnormalities
among HIV-Positive and HIV-Negative Women in Senegal, Africa.
AB - Background: There is evidence of an interaction between HIV and human
papillomavirus (HPV) resulting in increased HPV-associated morbidity and cancer
mortality among HIV-positive women. This study aims to determine how the natural
history of cervical HPV infection differs by HIV status.Methods: A total of 1,320
women (47% were positive for HIV-1 and/or HIV-2) were followed for an average of
two years in Senegal, West Africa between 1994 and 2010. Cytology (with a sub
sample of histology) and HPV DNA testing were performed at approximately 4-month
intervals yielding data from over 7,900 clinic visits. Competing risk modeling
was used to estimate rates for transitioning between three clinically relevant
natural history stages: Normal, HPV, and HSIL (high-grade squamous
intraepithelial lesions). Among HIV-positive women, exploratory univariate
analyses were conducted examining the impact of HPV type, infection with multiple
HPV types, HIV type, CD4+ count, and age.Results: HIV-positive women had higher
rates of progression and lower rates of regression compared with HIV-negative
women (i.e., adverse transitions). HIV-positive women had a 2.55 [95% confidence
interval (CI), 1.69-3.86; P < 0.0001] times higher rate of progression from HPV
to HSIL than HIV-negative women (with 24-month absolute risks of 0.18 and 0.07,
respectively). Among HIV-positive women, HPV-16/18 infection and CD4+ count
<200/mm3 were associated with adverse transitions.Conclusions: Adverse HIV
effects persist throughout HPV natural history stages.Impact: In the limited
resource setting of sub-Saharan Africa where cervical cancer screening is not
widely available, the high-risk population of HIV-positive women may be ideal for
targeted screening. Cancer Epidemiol Biomarkers Prev; 26(6); 886-94. (c)2017
AACR.
PMID- 28515110
TI - Do Men and Women Need to Be Screened Differently with Fecal Immunochemical
Testing? A Cost-Effectiveness Analysis.
AB - Background: Several studies suggest that test characteristics for the fecal
immunochemical test (FIT) differ by gender, triggering a debate on whether men
and women should be screened differently. We used the microsimulation model
MISCAN-Colon to evaluate whether screening stratified by gender is cost
effective.Methods: We estimated gender-specific FIT characteristics based on
first-round positivity and detection rates observed in a FIT screening pilot
(CORERO-1). Subsequently, we used the model to estimate harms, benefits, and
costs of 480 gender-specific FIT screening strategies and compared them with
uniform screening.Results: Biennial FIT screening from ages 50 to 75 was less
effective in women than men [35.7 vs. 49.0 quality-adjusted life years (QALY)
gained, respectively] at higher costs (?42,161 vs. -?5,471, respectively).
However, the incremental QALYs gained and costs of annual screening compared with
biennial screening were more similar for both genders (8.7 QALYs gained and
?26,394 for women vs. 6.7 QALYs gained and ?20,863 for men). Considering all
evaluated screening strategies, optimal gender-based screening yielded at most 7%
more QALYs gained than optimal uniform screening and even resulted in equal costs
and QALYs gained from a willingness-to-pay threshold of ?1,300.Conclusions: FIT
screening is less effective in women, but the incremental cost-effectiveness is
similar in men and women. Consequently, screening stratified by gender is not
more cost-effective than uniform FIT screening.Impact: Our conclusions support
the current policy of uniform FIT screening. Cancer Epidemiol Biomarkers Prev;
26(8); 1328-36. (c)2017 AACR.
PMID- 28515111
TI - Racial Differences in Adjuvant Endocrine Therapy Use and Discontinuation in
Association with Mortality among Medicare Breast Cancer Patients by Receptor
Status.
AB - Background: There are racial disparities in breast cancer mortality. Our purpose
was to determine whether racial/ethnic differences in use and discontinuation of
adjuvant endocrine therapy (AET) differed by hormone receptor status and whether
discontinuation was associated with mortality.Methods: We conducted a
retrospective cohort study with SEER/Medicare dataset of women age >=65 years
diagnosed with stage I-III breast cancer in Medicare Part-D from 2007 to 2009,
stratified by hormone receptor status. We performed multivariable logistic
regressions to assess racial differences for the odds of AET initiation and Cox
proportional hazards models to determine the risk of discontinuation and
mortality.Results: Of 14,902 women, 64.5% initiated AET <12 months of diagnosis.
Among those with hormone receptor-positive cancer, 74.8% initiated AET compared
with 5.6% of women with negative and 54.0% with unknown-receptor status. Blacks
were less likely to initiate [OR, 0.76; 95% confidence interval (CI), 0.66-0.88]
compared with whites. However, those with hormone receptor-positive disease were
less likely to discontinue (HR, 0.89; 95% CI, 0.80-0.98). Women who initiated
with aromatase inhibitors had increased risk of discontinuation compared with
women who initiated tamoxifen (HR, 1.12; 95% CI, 1.05-1.20). Discontinuation
within 12 months was associated with higher risk of all-cause (HR, 1.75; 95% CI,
1.74-2.00) and cancer-specific mortality (HR, 2.76; 95% CI, 1.74-4.38) after
controlling for race/ethnicity.Conclusions: There are racial/ethnic differences
in AET use and discontinuation. Discontinuing treatment was associated with
higher risk of all-cause and cancer-specific mortality regardless of hormone
receptor status.Impact: This study underscores the need to study factors that
influence discontinuation and the survival benefits of receiving AET for hormone
receptor-negative breast cancer. Cancer Epidemiol Biomarkers Prev; 26(8); 1266
75. (c)2017 AACR.
PMID- 28515112
TI - Impact of the Metabolic Syndrome on Mortality is Modified by Objective Short
Sleep Duration.
AB - BACKGROUND: To examine whether objective sleep duration is an effect modifier of
the impact of metabolic syndrome (MetS) on all-cause and cardiovascular
disease/cerebrovascular mortality. METHODS AND RESULTS: We addressed this
question in the Penn State Adult Cohort, a random, general population sample of
1344 men and women (48.8+/-14.2 years) who were studied in the sleep laboratory
and followed up for 16.6+/-4.2 years. MetS was defined by the presence of 3 or
more of obesity (>=30 kg/m2), elevated total cholesterol (>=200 mg/dL),
triglycerides (>=150 mg/dL), fasting glucose (>=100 mg/dL), and blood pressure
(>=130/85 mm Hg). Polysomnographic sleep duration was classified into clinically
meaningful categories. Among the 1344 participants, 22.0% of them died during the
follow-up. We tested the interaction between MetS and polysomnographic sleep
duration on mortality using Cox proportional hazard models controlling for
multiple potential confounders (P<0.05). The hazard ratios (95% CI) of all-cause
and cardiovascular disease/cerebrovascular mortality associated with MetS were
1.29 (0.89-1.87) and 1.49 (0.75-2.97) for individuals who slept >=6 hours and
1.99 (1.53-2.59) and 2.10 (1.39-3.16) for individuals who slept <6 hours.
Interestingly, this effect modification was primarily driven by the elevated
blood pressure and glucose dysregulation components of MetS. CONCLUSIONS: The
risk of mortality associated with MetS is increased in those with short sleep
duration. Short sleep in individuals with MetS may be linked to greater central
autonomic and metabolic dysfunction. Future clinical trials should examine
whether lengthening sleep improves the prognosis of individuals with MetS.
PMID- 28515113
TI - Force-Sensing Catheters During Pediatric Radiofrequency Ablation: The FEDERATION
Study.
AB - BACKGROUND: Based on data from studies of atrial fibrillation ablations, optimal
parameters for the TactiCath (TC; St. Jude Medical, Inc) force-sensing ablation
catheter are a contact force of 20 g and a force-time integral of 400 g.s for the
creation of transmural lesions. We aimed to evaluate TC in pediatric and
congenital heart disease patients undergoing ablation. METHODS AND RESULTS:
Comprehensive chart and case reviews were performed from June 2015 to March 2016.
Of the 102 patients undergoing electrophysiology study plus ablation, 58 (57%)
underwent ablation initially with a force-sensing catheter. Patients had an
average age of 14 (2.4-23) years and weight of 58 (18-195) kg with 15 patients
having abnormal cardiac anatomy. Electrophysiology diagnoses for the +TC group
included 30 accessory pathway-mediated tachycardia, 24 atrioventricular nodal
reentrant tachycardia, and 7 other. Baseline generator settings included a power
of 20 W, temperature of 40 degrees , and 6 cc/min flow during lesion creation
with 11 patients (19%) having alterations to parameters. Seventeen patients (30%)
converted to an alternate ablation source. A total of 516 lesions were performed
using the TC with a median contact force of 6 g, force-time integral of 149 g.s,
and lesion size index of 3.3. Median-term follow-up demonstrated 5 (10%)
recurrences with no acute or median-term complications. CONCLUSIONS: TactiCath
can be effectively employed in the treatment of pediatric patients with
congenital heart disease with lower forces than previously described in the
atrial fibrillation literature. Patients with atrioventricular nodal reentrant
tachycardia or atrioventricular reciprocating tachycardia may not require
transmural lesions and the TC may provide surrogate markers for success during
slow pathway ablation.
PMID- 28515114
TI - Cardiopulmonary Resuscitation Training Disparities in the United States.
AB - BACKGROUND: Bystander cardiopulmonary resuscitation (CPR) is associated with
increased survival from cardiac arrest, yet bystander CPR rates are low in many
communities. The overall prevalence of CPR training in the United States and
associated individual-level disparities are unknown. We sought to measure the
national prevalence of CPR training and hypothesized that older age and lower
socioeconomic status would be independently associated with a lower likelihood of
CPR training. METHODS AND RESULTS: We administered a cross-sectional telephone
survey to a nationally representative adult sample. We assessed the demographics
of individuals trained in CPR within 2 years (currently trained) and those who
had been trained in CPR at some point in time (ever trained). The association of
CPR training and demographic variables were tested using survey weighted logistic
regression. Between September 2015 and November 2015, 9022 individuals completed
the survey; 18% reported being currently trained in CPR, and 65% reported
training at some point previously. For each year of increased age, the likelihood
of being currently CPR trained or ever trained decreased (currently trained: odds
ratio, 0.98; 95% CI, 0.97-0.99; P<0.01; ever trained: OR, 0.99; 95% CI, 0.98
0.99; P=0.04). Furthermore, there was a greater then 4-fold difference in odds of
being currently CPR trained from the 30-39 to 70-79 year old age groups (95% CI,
0.10-0.23). Factors associated with a lower likelihood of CPR training were
lesser educational attainment and lower household income (P<0.01 for each of
these variables). CONCLUSIONS: A minority of respondents reported current
training in CPR. Older age, lesser education, and lower income were associated
with reduced likelihood of CPR training. These findings illustrate important gaps
in US CPR education and suggest the need to develop tailored CPR training efforts
to address this variability.
PMID- 28515115
TI - Impact of Antihypertensive Treatment on Maternal and Perinatal Outcomes in
Pregnancy Complicated by Chronic Hypertension: A Systematic Review and Meta
Analysis.
AB - BACKGROUND: Chronic hypertension complicates around 3% of all pregnancies. There
is evidence that treating severe hypertension reduces maternal morbidity. This
study aimed to systematically review randomized controlled trials of
antihypertensive agents treating chronic hypertension in pregnancy to determine
the effect of this intervention. METHODS AND RESULTS: Medline (via OVID), Embase
(via OVID) and the Cochrane Trials Register were searched from their earliest
entries until November 30, 2016. All randomized controlled trials evaluating
antihypertensive treatments for chronic hypertension in pregnancy were included.
Data were extracted and analyzed in Stata (version 14.1). Fifteen randomized
controlled trials (1166 women) were identified for meta-analysis. A clinically
important reduction in the incidence of severe hypertension was seen with
antihypertensive treatment versus no antihypertensive treatment/placebo (5
studies, 446 women; risk ratio 0.33, 95%CI 0.19-0.56; I2 0.0%). There was no
difference in the incidence of superimposed pre-eclampsia (7 studies, 727 women;
risk ratio 0.74, 95%CI 0.49-1.11; I2 28.1%), stillbirth/neonatal death (4
studies, 667 women; risk ratio 0.37, 95%CI 0.11-1.26; I2 0.0%), birth weight (7
studies, 802 women; weighted mean difference -60 g, 95%CI -200 to 80 g; I2 0.0%),
or small for gestational age (4 studies, 369 women; risk ratio 1.01, 95%CI 0.53
1.94; I2 0.0%) with antihypertensive treatment versus no treatment/placebo.
CONCLUSIONS: Antihypertensive treatment reduces the risk of severe hypertension
in pregnant women with chronic hypertension. A considerable paucity of data
exists to guide choice of antihypertensive agent. Adequately powered head-to-head
randomized controlled trials of commonly used antihypertensive agents are
required to inform prescribing.
PMID- 28515117
TI - Venous Thromboembolism Risk With Antidepressants: Driven by Disease or Drugs?
PMID- 28515116
TI - Antidepressants, Depression, and Venous Thromboembolism Risk: Large Prospective
Study of UK Women.
AB - BACKGROUND: Some investigators have reported an excess risk of venous
thromboembolism (VTE) associated with depression and with use of antidepressant
drugs. We explored these associations in a large prospective study of UK women.
METHODS AND RESULTS: The Million Women Study recruited 1.3 million women through
the National Health Service Breast Screening Programme in England and Scotland.
Three years after recruitment, women were sent a second questionnaire that
enquired about depression and regular use of medications in the previous 4 weeks.
The present analysis included those who responded and did not have prior VTE,
cancer, or recent surgery. Follow-up for VTE was through linkage to routinely
collected National Health Service statistics. Cox regression analyses yielded
adjusted hazard ratios and 95% CIs. A total of 734 092 women (mean age 59.9
years) were included in the analysis; 6.9% reported use of antidepressants, 2.7%
reported use of other psychotropic drugs, and 1.8% reported being treated for
depression or anxiety but not use of psychotropic drugs. During follow-up for an
average of 7.3 years, 3922 women were hospitalized for and/or died from VTE.
Women who reported antidepressant use had a significantly higher risk of VTE than
women who reported neither depression nor use of psychotropic drugs (hazard
ratio, 1.39; 95% CI, 1.23-1.56). VTE risk was not significantly increased in
women who reported being treated for depression or anxiety but no use of
antidepressants or other psychotropic drugs (hazard ratio, 1.19; 95% CI, 0.95
1.49). CONCLUSIONS: Use of antidepressants is common in UK women and is
associated with an increased risk of VTE.
PMID- 28515118
TI - Risk Factors for Heart Failure in Patients With Chronic Kidney Disease: The CRIC
(Chronic Renal Insufficiency Cohort) Study.
AB - BACKGROUND: Heart failure is common in patients with chronic kidney disease. We
studied risk factors for incident heart failure among 3557 participants in the
CRIC (Chronic Renal Insufficiency Cohort) Study. METHODS AND RESULTS: Kidney
function was assessed by estimated glomerular filtration rate (eGFR) using serum
creatinine, cystatin C, or both, and 24-hour urine albumin excretion. During an
average of 6.3 years of follow-up, 452 participants developed incident heart
failure. After adjustment for age, sex, race, and clinical site, hazard ratio
(95% CI) for heart failure associated with 1 SD lower creatinine-based eGFR was
1.67 (1.49, 1.89), 1 SD lower cystatin C-based-eGFR was 2.43 (2.10, 2.80), and 1
SD higher log-albuminuria was 1.65 (1.53, 1.78), all P<0.001. When all 3 kidney
function measures were simultaneously included in the model, lower cystatin C
based eGFR and higher log-albuminuria remained significantly and directly
associated with incidence of heart failure. After adjusting for eGFR,
albuminuria, and other traditional cardiovascular risk factors, anemia (1.37, 95%
CI 1.09, 1.72, P=0.006), insulin resistance (1.16, 95% CI 1.04, 1.28, P=0.006),
hemoglobin A1c (1.27, 95% CI 1.14, 1.41, P<0.001), interleukin-6 (1.15, 95% CI
1.05, 1.25, P=0.002), and tumor necrosis factor-alpha (1.10, 95% CI 1.00, 1.21,
P=0.05) were all significantly and directly associated with incidence of heart
failure. CONCLUSIONS: Our study indicates that cystatin C-based eGFR and
albuminuria are better predictors for risk of heart failure compared to
creatinine-based eGFR. Furthermore, anemia, insulin resistance, inflammation, and
poor glycemic control are independent risk factors for the development of heart
failure among patients with chronic kidney disease.
PMID- 28515119
TI - Pulse Wave Velocity Predicts Response to Renal Denervation in Isolated Systolic
Hypertension.
AB - BACKGROUND: Renal sympathetic denervation seems to be less effective as a
treatment for hypertension in patients with isolated systolic hypertension, a
condition associated with elevated central arterial stiffness. Because isolated
systolic hypertension can also be caused by wave reflection or increased cardiac
output, a more differentiated approach might improve patient preselection for
renal sympathetic denervation. We sought to evaluate the additional predictive
value of invasive pulse wave velocity for response to renal sympathetic
denervation in patients with combined versus isolated systolic hypertension.
METHODS AND RESULTS: Patients scheduled for renal sympathetic denervation
underwent additional invasive measurement of pulse wave velocity and pulse
pressure before denervation. Blood pressure was assessed via ambulatory
measurement at baseline and after 3 months. In total 109 patients (40 patients
with isolated systolic hypertension) were included in our analysis. After 3
months, blood pressure reduction was more pronounced among patients with combined
hypertension compared with patients with isolated systolic hypertension (systolic
24-hour average 9.3+/-10.5 versus 5.0+/-11.5 mm Hg, P=0.046). However, when
stratifying patients with isolated systolic hypertension by invasive pulse wave
velocity, patients in the lowest tertile of pulse wave velocity had comparable
blood pressure reduction (12.1+/-12.6 mm Hg, P=0.006) despite lower baseline
blood pressure than patients with combined hypertension (systolic 24-hour average
154.8+/-12.5 mm Hg in combined hypertension versus 141.2+/-8.1, 148.4+/-10.9, and
150.5+/-12.7 mm Hg, respectively, by tertiles of pulse wave velocity, P=0.002).
CONCLUSIONS: Extended assessment of arterial stiffness can help improve patient
preselection for renal sympathetic denervation and identify a subgroup of
isolated systolic hypertension patients who benefit from sympathetic modulation.
PMID- 28515122
TI - Sixty seconds on . . . pagers.
PMID- 28515120
TI - Remote Ischemic Perconditioning to Reduce Reperfusion Injury During Acute ST
Segment-Elevation Myocardial Infarction: A Systematic Review and Meta-Analysis.
AB - BACKGROUND: Remote ischemic conditioning (RIC) is a noninvasive therapeutic
strategy that uses brief cycles of blood pressure cuff inflation and deflation to
protect the myocardium against ischemia-reperfusion injury. The objective of this
systematic review was to determine the impact of RIC on myocardial salvage index,
infarct size, and major adverse cardiovascular events when initiated before
catheterization. METHODS AND RESULTS: Electronic searches of Medline, Embase, and
Cochrane Central Register of Controlled Trials were conducted and reference lists
were hand searched. Randomized controlled trials comparing percutaneous coronary
intervention (PCI) with and without RIC for patients with ST-segment-elevation
myocardial infarction were included. Two reviewers independently screened
abstracts, assessed quality of the studies, and extracted data. Data were pooled
using random-effects models and reported as mean differences and relative risk
with 95% confidence intervals. Eleven articles (9 randomized controlled trials)
were included with a total of 1220 patients (RIC+PCI=643, PCI=577). Studies with
no events were excluded from meta-analysis. The myocardial salvage index was
higher in the RIC+PCI group compared with the PCI group (mean difference: 0.08;
95% confidence interval, 0.02-0.14). Infarct size was reduced in the RIC+PCI
group compared with the PCI group (mean difference: -2.46; 95% confidence
interval, -4.66 to -0.26). Major adverse cardiovascular events were lower in the
RIC+PCI group (9.5%) compared with the PCI group (17.0%; relative risk: 0.57; 95%
confidence interval, 0.40-0.82). CONCLUSIONS: RIC appears to be a promising
adjunctive treatment to PCI for the prevention of reperfusion injury in patients
with ST-segment-elevation myocardial infarction; however, additional high-quality
research is required before a change in practice can be considered.
PMID- 28515125
TI - Britain without the EMA.
PMID- 28515124
TI - Your vote counts: how will a soft or hard Brexit affect health?
PMID- 28515123
TI - All-Trans Retinoic Acid Prevents Osteosarcoma Metastasis by Inhibiting M2
Polarization of Tumor-Associated Macrophages.
AB - M2-polarized tumor-associated macrophages (TAM) play a critical role in cancer
invasion and metastasis. Here, we report that M2 macrophages enhanced metastasis
of K7M2 WT osteosarcoma cells to the lungs in mice, thus establishing M2 TAMs as
a therapeutic target for blocking osteosarcoma metastasis. We found that all
trans retinoic acid (ATRA) inhibited osteosarcoma metastasis via inhibiting the
M2 polarization of TAMs. ATRA suppressed IL13- or IL4-induced M2-type
macrophages, and then inhibited migration of osteosarcoma cells as promoted by M2
type macrophages in vitro ATRA reduced the number of pulmonary metastatic nodes
of osteosarcoma and decreased expression of M2-type macrophages in metastatic
nodes both in intravenous injection and orthotopic transplantation models. ATRA's
effect was independent of conventional STAT3/6 or C/EBPbeta signaling, which
regulate M2-like polarization of macrophages. Quantitative genomic and functional
analyses revealed that MMP12, a macrophage-secreted elastase, was elevated in
IL13-skewed TAM polarization, whereas ATRA treatment downregulated IL13-induced
secretion of MMP12. This downregulation correlates with the antimetastasis effect
of ATRA. Our results show the role of TAM polarization in osteosarcoma
metastasis, identify a therapeutic opportunity for antimetastasis treatment, and
indicate ATRA treatment as an approach for preventing osteosarcoma metastasis via
M2-type polarization intervention. Cancer Immunol Res; 5(7); 547-59. (c)2017
AACR.
PMID- 28515127
TI - A retrospective analysis of mitral valve pathology in the setting of bicuspid
aortic valves.
AB - The therapeutic implications of bicuspid aortic valve associations have come
under scrutiny in the transcatheter aortic valve implantation era. We evaluate
the spectrum of mitral valve disease in patients with bicuspid aortic valves to
determine the need for closer echocardiographic scrutiny/follow-up of the mitral
valve. A retrospective analysis of echocardiograms done at a referral hospital
over five years was conducted in patients with bicuspid aortic valves with
special attention to congenital abnormalities of the mitral valve. One hundred
and forty patients with a bicuspid aortic valve were included. A congenital
mitral valve abnormality was present in eight (5.7%, P = 0.01) with a parachute
mitral valve in four (2.8%), an accessory mitral valve leaflet in one (0.7%),
mitral valve prolapse in one, a cleft in one and the novel finding of a
trileaflet mitral valve in one. Minor abnormalities included an elongated
anterior mitral valve leaflet (P < 0.001), the increased incidence of
physiological mitral regurgitation (P < 0.001), abnormal papillary muscles (P =
0.002) and an additional chord or tendon in the left ventricle cavity (P =
0.007). Mitral valve abnormalities occur more commonly in patients with bicuspid
aortic valves than matched healthy individuals. The study confirms that
abnormalities in these patients extend beyond the aorta. These abnormalities did
not have a significant functional effect.
PMID- 28515121
TI - AMPKalpha1-LDH pathway regulates muscle stem cell self-renewal by controlling
metabolic homeostasis.
AB - Control of stem cell fate to either enter terminal differentiation versus
returning to quiescence (self-renewal) is crucial for tissue repair. Here, we
showed that AMP-activated protein kinase (AMPK), the master metabolic regulator
of the cell, controls muscle stem cell (MuSC) self-renewal. AMPKalpha1-/- MuSCs
displayed a high self-renewal rate, which impairs muscle regeneration. AMPKalpha1
/- MuSCs showed a Warburg-like switch of their metabolism to higher glycolysis.
We identified lactate dehydrogenase (LDH) as a new functional target of
AMPKalpha1. LDH, which is a non-limiting enzyme of glycolysis in differentiated
cells, was tightly regulated in stem cells. In functional experiments, LDH
overexpression phenocopied AMPKalpha1-/- phenotype, that is shifted MuSC
metabolism toward glycolysis triggering their return to quiescence, while
inhibition of LDH activity rescued AMPKalpha1-/- MuSC self-renewal. Finally,
providing specific nutrients (galactose/glucose) to MuSCs directly controlled
their fate through the AMPKalpha1/LDH pathway, emphasizing the importance of
metabolism in stem cell fate.
PMID- 28515128
TI - Correction for Iwasaki et al., "Homolactic Acid Fermentation by the Genetically
Engineered Thermophilic Homoacetogen Moorella thermoacetica ATCC 39073".
PMID- 28515126
TI - Radiomanganese PET Detects Changes in Functional beta-Cell Mass in Mouse Models
of Diabetes.
AB - The noninvasive measurement of functional beta-cell mass would be clinically
valuable for monitoring the progression of type 1 and type 2 diabetes as well as
the viability of transplanted insulin-producing cells. Although previous work
using MRI has shown promise for functional beta-cell mass determination through
voltage-dependent Ca2+ channel (VDCC)-mediated internalization of Mn2+, the
clinical utility of this technique is limited by the cytotoxic levels of the Mn2+
contrast agent. Here, we show that positron emission tomography (PET) is
advantageous for determining functional beta-cell mass using 52Mn2+ (t1/2: 5.6
days). We investigated the whole-body distribution of 52Mn2+ in healthy adult
mice by dynamic and static PET imaging. Pancreatic VDCC uptake of 52Mn2+ was
successfully manipulated pharmacologically in vitro and in vivo using glucose,
nifedipine (VDCC blocker), the sulfonylureas tolbutamide and glibenclamide (KATP
channel blockers), and diazoxide (KATP channel opener). In a mouse model of
streptozotocin-induced type 1 diabetes, 52Mn2+ uptake in the pancreas was
distinguished from healthy controls in parallel with classic histological
quantification of beta-cell mass from pancreatic sections. 52Mn2+-PET also
reported the expected increase in functional beta-cell mass in the ob/ob model of
pretype 2 diabetes, a result corroborated by histological beta-cell mass
measurements and live-cell imaging of beta-cell Ca2+ oscillations. These results
indicate that 52Mn2+-PET is a sensitive new tool for the noninvasive assessment
of functional beta-cell mass.
PMID- 28515130
TI - Erratum for Pandey et al., "Intracellular pH Response to Weak Acid Stress in
Individual Vegetative Bacillus subtilis Cells".
PMID- 28515131
TI - Exenatide Improves HDL Particle Counts and Size Distribution in Patients With
Long-standing Type 1 Diabetes.
PMID- 28515132
TI - Inclusion of emergency department patients in early stages of sepsis in a quality
improvement programme has the potential to improve survival: a prospective dual
centre study.
AB - STUDY OBJECTIVE: Sepsis quality improvement programmes typically focus on severe
sepsis (ie, with acute organ failure). However, quality of ED care might be
improved if these programmes included patients whose progression to severe sepsis
could still be prevented (ie, infection without acute organ failure). We compared
the impact on mortality of implementing a quality improvement programme among ED
patients with a suspected infection with or without acute organ failure. METHODS:
This prospective observational study among ED patients hospitalised with
suspected infection was conducted in two hospitals in the Netherlands. After
stratification by sepsis category (with or without organ failure), in-hospital
mortality was compared between a full compliance (all quality performance
measures achieved) and an incomplete compliance group. Multivariable logistic
regression analysis was used to quantify the impact of full compliance on in
hospital mortality, adjusting for disease severity, disposition and hospital.
RESULTS: There were 1732 ED patients and 130 deaths. Full compliance was
independently associated with approximately two-thirds reduction in the odds of
hospital mortality (adjusted OR of 0.30 (95% CI 0.19 to 0.47), which was similar
in patients with and without organ failure. Among the 1379 patients with
suspected infection without acute organ failure, there were 64 deaths, 15 (1.1%)
in the full compliance group and 49 (3.6%) in the incomplete compliance group
(mortality difference 2.5% (95% CI 1.6% to 3.3%)). Among 353 patients with organ
failure, there were 66 deaths, 12 (3.4%) in the full compliance compared with 54
(15.3%) in the incomplete compliance group (mortality difference 11.9% (95% CI
8.5% to 15.3%)). Thus, there was a difference of 76 deaths between full and
incomplete compliance groups, and 34 (45%) who benefited were those without acute
organ failure. CONCLUSIONS: Sepsis quality improvement programmes should
incorporate ED patients in earlier stages of sepsis given the potential to reduce
in-hospital mortality among this population.
PMID- 28515133
TI - Development of a Novel Virus-Like Particle Vaccine Platform That Mimics the
Immature Form of Alphavirus.
AB - Virus-like particles (VLPs) are noninfectious multiprotein structures that are
engineered to self-assemble from viral structural proteins. Here, we developed a
novel VLP-based vaccine platform utilizing VLPs from the chikungunya virus. We
identified two regions within the envelope protein, a structural component of
chikungunya, where foreign antigens can be inserted without compromising VLP
structure. Our VLP displays 480 copious copies of an inserted antigen on the VLP
surface in a highly symmetric manner and is thus capable of inducing strong
immune responses against any inserted antigen. Furthermore, by mimicking the
structure of the immature form of the virus, we altered our VLP's in vivo
dynamics and enhanced its immunogenicity. We used the circumsporozoite protein
(CSP) of the Plasmodium falciparum malaria parasite as an antigen and
demonstrated that our VLP-based vaccine elicits strong immune responses against
CSP in animals. The sera from immunized monkeys protected mice from malaria
infection. Likewise, mice vaccinated with P. yoelii CSP-containing VLPs were
protected from an infectious sporozoite challenge. Hence, our uniquely engineered
VLP platform can serve as a blueprint for the development of vaccines against
other pathogens and diseases.
PMID- 28515134
TI - Identification of Novel Seroreactive Antigens in Johne's Disease Cattle by Using
the Mycobacterium tuberculosis Protein Array.
AB - Johne's disease, a chronic gastrointestinal inflammatory disease caused by
Mycobacterium avium subspecies paratuberculosis, is endemic in dairy cattle and
other ruminants worldwide and remains a challenge to diagnose using traditional
serological methods. Given the close phylogenetic relationship between M. avium
subsp. paratuberculosis and the human pathogen Mycobacterium tuberculosis, here,
we applied a whole-proteome M. tuberculosis protein array to identify
seroreactive and diagnostic M. avium subsp. paratuberculosis antigens. A genome
scale pairwise analysis of amino acid identity levels between orthologous
proteins in M. avium subsp. paratuberculosis and M. tuberculosis showed an
average of 62% identity, with more than half the orthologous proteins sharing
>75% identity. Analysis of the M. tuberculosis protein array probed with sera
from M. avium subsp. paratuberculosis-infected cattle showed antibody binding to
729 M. tuberculosis proteins, with 58% of them having >=70% identity to M. avium
subsp. paratuberculosis orthologs. The results showed that only 4 of the top 40
seroreactive M. tuberculosis antigens were orthologs of previously reported M.
avium subsp. paratuberculosis antigens, revealing the existence of a large number
of previously unrecognized candidate diagnostic antigens. Enzyme-linked
immunosorbent assay (ELISA) testing of 20 M. avium subsp. paratuberculosis
recombinant proteins, representing reactive and nonreactive M. tuberculosis
orthologs, further confirmed that the M. tuberculosis array has utility as a
screening tool for identifying candidate antigens for Johne's disease
diagnostics. Additional ELISA testing of field serum samples collected from dairy
herds around the United States revealed that MAP2942c had the strongest
seroreactivity with Johne's disease-positive samples. Collectively, our studies
have considerably expanded the number of candidate M. avium subsp.
paratuberculosis proteins with potential utility in the next generation of
rationally designed Johne's disease diagnostic assays.
PMID- 28515135
TI - Not All Antigens Are Created Equally: Progress, Challenges, and Lessons
Associated with Developing a Vaccine for Leishmaniasis.
AB - From experimental models and the analyses of patients, it is well documented that
antigen-specific T cells are critical for protection against Leishmania
infection. Effective vaccines require both targeting to the pathogen and an
immune stimulant to induce maturation of appropriate immune responses. While a
great number of antigens have been examined as vaccine candidates against various
Leishmania species, few have advanced to human or canine clinical trials. With
emphasis on antigen expression, in this minireview we discuss some of the vaccine
platforms that are currently being explored for the development of Leishmania
vaccines. It is clear that the vaccine platform of choice can have a significant
impact upon the level of protection induced by particular antigens, and we
provide and highlight some examples for which the vaccine system used has
impacted the protective efficacy imparted.
PMID- 28515136
TI - Loss of Humoral and Cellular Immunity to Invasive Nontyphoidal Salmonella during
Current or Convalescent Plasmodium falciparum Infection in Malawian Children.
AB - Invasive nontyphoidal Salmonella (iNTS) infections are commonly associated with
Plasmodium falciparum infections, but the immunologic basis for this linkage is
poorly understood. We hypothesized that P. falciparum infection compromises the
humoral and cellular immunity of the host to NTS, which increases the
susceptibility of the host to iNTS infection. We prospectively recruited children
aged between 6 and 60 months at a Community Health Centre in Blantyre, Malawi,
and allocated them to the following groups; febrile with uncomplicated malaria,
febrile malaria negative, and nonfebrile malaria negative. Levels of Salmonella
enterica serovar Typhimurium-specific serum bactericidal activity (SBA) and whole
blood bactericidal activity (WBBA), complement C3 deposition, and neutrophil
respiratory burst activity (NRBA) were measured. Levels of SBA with respect to S
Typhimurium were reduced in febrile P. falciparum-infected children (median,
0.20 log10 [interquartile range {IQR}, -1.85, 0.32]) compared to nonfebrile
malaria-negative children (median, -1.42 log10 [IQR, -2.0, -0.47], P = 0.052). In
relation to SBA, C3 deposition on S Typhimurium was significantly reduced in
febrile P. falciparum-infected children (median, 7.5% [IQR, 4.1, 15.0]) compared
to nonfebrile malaria-negative children (median, 29% [IQR, 11.8, 48.0], P =
0.048). WBBA with respect to S Typhimurium was significantly reduced in febrile
P. falciparum-infected children (median, 0.25 log10 [IQR, -0.73, 1.13], P =
0.0001) compared to nonfebrile malaria-negative children (median, -1.0 log10
[IQR, -1.68, -0.16]). In relation to WBBA, S Typhimurium-specific NRBA was
reduced in febrile P. falciparum-infected children (median, 8.8% [IQR, 3.7, 20],
P = 0.0001) compared to nonfebrile malaria-negative children (median, 40.5% [IQR,
33, 65.8]). P. falciparum infection impairs humoral and cellular immunity to S
Typhimurium in children during malaria episodes, which may explain the increased
risk of iNTS observed in children from settings of malaria endemicity. The
mechanisms underlying humoral immunity impairment are incompletely understood and
should be explored further.
PMID- 28515137
TI - Under the influence: examination of prevalence and correlates of alcohol and
marijuana consumption in relation to youth driving and passenger behaviours in
Canada. A cross-sectional study.
AB - BACKGROUND: Consequences of alcohol- and drug-impaired driving affect youth
disproportionately. We describe individual- and area-level characteristics
associated with risky driving and passenger behaviours among grade 9-12 students
in Canada. METHODS: The 2014-2015 Canadian Student Tobacco, Alcohol and Drug
Survey was administered to 24 650 students in provincially generalizable samples.
Dichotomous outcomes included ever and last-30-day driving after drinking
alcohol, ever and last-30-day driving after using marijuana, and ever and last-30
day reporting of being a passenger with a driver who had been drinking or using
marijuana. RESULTS: A total of 9.1% (99% confidence interval 7.9-10.3) of grade
11-12 students reported ever driving after drinking, and 9.4% (99% confidence
interval 8.3-10.4) reported ever driving after using marijuana. Almost half (48%)
of grade 11-12 students reported ever participating in any risky driving or
passenger behaviour. Over one-third (35%) of grade 9-12 students reported ever
riding with a driver who had been drinking, and 20% reported ever riding with a
driver who had been using marijuana. Logistic regression models showed that boys
had higher odds of risky driving behaviours relative to girls, whereas girls had
higher odds of risky passenger behaviours relative to boys. Students from rural
schools had higher odds of drinking and driving and of riding with a driver who
had drunk relative to students from urban schools. There were significant
differences in risky driving and passenger behaviours by province.
INTERPRETATION: A substantial number of Canadian youth reported risky driving and
passenger behaviours, which varied by individual and area-level characteristics.
Federal marijuana policy should aim to reduce the prevalence of drug-impaired
driving. Additional provincial policies to prevent impaired driving are needed.
PMID- 28515138
TI - Dalcetrapib and anacetrapib differently impact HDL structure and function in
rabbits and monkeys.
AB - Inhibition of cholesteryl ester transfer protein (CETP) increases HDL cholesterol
(HDL-C) levels. However, the circulating CETP level varies and the impact of its
inhibition in species with high CETP levels on HDL structure and function remains
poorly characterized. This study investigated the effects of dalcetrapib and
anacetrapib, the two CETP inhibitors (CETPis) currently being tested in large
clinical outcome trials, on HDL particle subclass distribution and cholesterol
efflux capacity of serum in rabbits and monkeys. New Zealand White rabbits and
vervet monkeys received dalcetrapib and anacetrapib. In rabbits, CETPis increased
HDL-C, raised small and large alpha-migrating HDL, and increased ABCA1-induced
cholesterol efflux. In vervet monkeys, although anacetrapib produced similar
results, dalcetrapib caused opposite effects because the LDL-C level was
increased by 42% and HDL-C decreased by 48% (P < 0.01). The levels of alpha- and
prebeta-HDL were reduced by 16% (P < 0.001) and 69% (P < 0.01), resulting in a
decrease of the serum cholesterol efflux capacity. CETPis modulate the plasma
levels of mature and small HDL in vivo and consequently the cholesterol efflux
capacity. The opposite effects of dalcetrapib in different species indicate that
its impact on HDL metabolism could vary greatly according to the metabolic
environment.
PMID- 28515139
TI - Changes in ceramide metabolism are essential in Madin-Darby canine kidney cell
differentiation.
AB - Ceramides (Cers) and complex sphingolipids with defined acyl chain lengths play
important roles in numerous cell processes. Six Cer synthase (CerS) isoenzymes
(CerS1-6) are the key enzymes responsible for the production of the diversity of
molecular species. In this study, we investigated the changes in sphingolipid
metabolism during the differentiation of Madin-Darby canine kidney (MDCK) cells.
By MALDI TOF TOF MS, we analyzed the molecular species of Cer, glucosylceramide
(GlcCer), lactosylceramide (LacCer), and SM in nondifferentiated and
differentiated cells (cultured under hypertonicity). The molecular species
detected were the same, but cells subjected to hypertonicity presented higher
levels of C24:1 Cer, C24:1 GlcCer, C24:1 SM, and C16:0 LacCer. Consistently with
the molecular species, MDCK cells expressed CerS2, CerS4, and CerS6, but with no
differences during cell differentiation. We next evaluated the different
synthesis pathways with sphingolipid inhibitors and found that cells subjected to
hypertonicity in the presence of amitriptyline, an inhibitor of acid
sphingomyelinase, showed decreased radiolabeled incorporation in LacCer and cells
did not develop a mature apical membrane. These results suggest that
hypertonicity induces the endolysosomal degradation of SM, generating the Cer
used as substrate for the synthesis of specific molecular species of
glycosphingolipids that are essential for MDCK cell differentiation.
PMID- 28515140
TI - Three-Year Impacts Of The Affordable Care Act: Improved Medical Care And Health
Among Low-Income Adults.
AB - Major policy uncertainty continues to surround the Affordable Care Act (ACA) at
both the state and federal levels. We assessed changes in health care use and
self-reported health after three years of the ACA's coverage expansion, using
survey data collected from low-income adults through the end of 2016 in three
states: Kentucky, which expanded Medicaid; Arkansas, which expanded private
insurance to low-income adults using the federal Marketplace; and Texas, which
did not expand coverage. We used a difference-in-differences model with a control
group and an instrumental variables model to provide individual-level estimates
of the effects of gaining insurance. By the end of 2016 the uninsurance rate in
the two expansion states had dropped by more than 20 percentage points relative
to the nonexpansion state. For uninsured people gaining coverage, this change was
associated with a 41-percentage-point increase in having a usual source of care,
a $337 reduction in annual out-of-pocket spending, significant increases in
preventive health visits and glucose testing, and a 23-percentage-point increase
in "excellent" self-reported health. Among adults with chronic conditions, we
found improvements in affordability of care, regular care for those conditions,
medication adherence, and self-reported health.
PMID- 28515141
TI - Glucagon-induced extracellular cAMP regulates hepatic lipid metabolism.
AB - Hormonal signals help to maintain glucose and lipid homeostasis in the liver
during the periods of fasting. Glucagon, a pancreas-derived hormone induced by
fasting, promotes gluconeogenesis through induction of intracellular cAMP
production. Glucagon also stimulates hepatic fatty acid oxidation but the
underlying mechanism is poorly characterized. Here we report that following the
acute induction of gluconeogenic genes Glucose 6 phosphatase (G6Pase) and
Phosphoenolpyruvate carboxykinase (Pepck) expression through cAMP-response
element-binding protein (CREB), glucagon triggers a second delayed phase of fatty
acid oxidation genes Acyl-coenzyme A oxidase (Aox) and Carnitine
palmitoyltransferase 1a (Cpt1a) expression via extracellular cAMP. Increase in
extracellular cAMP promotes PPARalpha activity through direct phosphorylation by
AMP-activated protein kinase (AMPK), while inhibition of cAMP efflux greatly
attenuates Aox and Cpt1a expression. Importantly, cAMP injection improves lipid
homeostasis in fasted mice and obese mice, while inhibition of cAMP efflux
deteriorates hepatic steatosis in fasted mice. Collectively, our results
demonstrate the vital role of glucagon-stimulated extracellular cAMP in the
regulation of hepatic lipid metabolism through AMPK-mediated PPARalpha
activation. Therefore, strategies to improve cAMP efflux could serve as potential
new tools to prevent obesity-associated hepatic steatosis.
PMID- 28515142
TI - Flow-induced endothelial cell alignment requires the RhoGEF Trio as a scaffold
protein to polarize active Rac1 distribution.
AB - Endothelial cells line the lumen of the vessel wall and are exposed to flow. In
linear parts of the vessel, the endothelial cells experience laminar flow,
resulting in endothelial cell alignment in the direction of flow, thereby
protecting the vessel wall from inflammation and permeability. In order for
endothelial cells to align, they undergo rapid remodeling of the actin
cytoskeleton by local activation of the small GTPase Rac1. However, it is not
clear whether sustained and local activation of Rac1 is required for long-term
flow-induced cell alignment. Using a FRET-based DORA Rac1 biosensor, we show that
local Rac1 activity remains for 12 h upon long-term flow. Silencing studies show
that the RhoGEF Trio is crucial for keeping active Rac1 at the downstream side of
the cell and, as a result, for long-term flow-induced cell alignment.
Surprisingly, Trio appears to be not involved in flow-induced activation of Rac1.
Our data show that flow induces Rac1 activity at the downstream side of the cell
in a Trio-dependent manner and that Trio functions as a scaffold protein rather
than a functional GEF under long-term flow conditions.
PMID- 28515143
TI - Cyclin C influences the timing of mitosis in fission yeast.
AB - The multiprotein Mediator complex is required for the regulated transcription of
nearly all RNA polymerase II-dependent genes. Mediator contains the Cdk8
regulatory subcomplex, which directs periodic transcription and influences cell
cycle progression in fission yeast. Here we investigate the role of CycC, the
cognate cyclin partner of Cdk8, in cell cycle control. Previous reports suggested
that CycC interacts with other cellular Cdks, but a fusion of CycC to Cdk8
reported here did not cause any obvious cell cycle phenotypes. We find that Cdk8
and CycC interactions are stabilized within the Mediator complex and the activity
of Cdk8-CycC is regulated by other Mediator components. Analysis of a mutant
yeast strain reveals that CycC, together with Cdk8, primarily affects M-phase
progression but mutations that release Cdk8 from CycC control also affect timing
of entry into S phase.
PMID- 28515144
TI - Transient activation of fission yeast AMPK is required for cell proliferation
during osmotic stress.
AB - The heterotrimeric kinase AMPK acts as an energy sensor to coordinate cell
metabolism with environmental status in species from yeast through humans. Low
intracellular ATP leads to AMPK activation through phosphorylation of the
activation loop within the catalytic subunit. Other environmental stresses also
activate AMPK, but it is unclear whether cellular energy status affects AMPK
activation under these conditions. Fission yeast AMPK catalytic subunit Ssp2 is
phosphorylated at Thr-189 by the upstream kinase Ssp1 in low-glucose conditions,
similar to other systems. Here we find that hyperosmotic stress induces strong
phosphorylation of Ssp2-T189 by Ssp1. Ssp2-pT189 during osmotic stress is
transient and leads to transient regulation of AMPK targets, unlike sustained
activation by low glucose. Cells lacking this activation mechanism fail to
proliferate after hyperosmotic stress. Activation during osmotic stress requires
energy sensing by AMPK heterotrimer, and osmotic stress leads to decreased
intracellular ATP levels. We observed mitochondrial fission during osmotic
stress, but blocking fission did not affect AMPK activation. Stress-activated
kinases Sty1 and Pmk1 did not promote AMPK activation but contributed to
subsequent inactivation. Our results show that osmotic stress induces transient
energy stress, and AMPK activation allows cells to manage this energy stress for
proliferation in new osmotic states.
PMID- 28515145
TI - Target RNA Secondary Structure Is a Major Determinant of miR159 Efficacy.
AB - In plants, microRNA (miRNA)-target complementarity has long been considered the
predominant factor determining the silencing outcome of the miRNA-target
interaction, although the efficacy of such interactions have rarely been
appraised in plants. Here, we perform in planta silencing efficacy assays on
seven Arabidopsis MYB genes, all of which contain conserved miR159-binding sites
of analogous complementarity. These genes were found to be differentially
silenced by miR159; MYB81, MYB97, MYB101, MYB104, and DUO1 were all poorly
silenced, whereas MYB33 and MYB65 were strongly silenced. Curiously, this is
consistent with previous genetic analysis defining MYB33 and MYB65 as the major
functional targets of miR159. Neither the free energy of miR159-target
complementarity, nor miRNA binding site accessibility, as determined by flanking
region AU content, could fully explain the discrepancy of miR159 silencing
efficacy. Instead, we found that MYB33 and MYB65 were both predicted to contain a
distinctive RNA secondary structure abutting the miR159 binding site. The
structure is composed of two stem-loops (SLs) that are predicted to form in
MYB33/65 homologs of species as evolutionary distant as gymnosperms. Functional
analysis found that the RNA structure in MYB33 correlated with strong silencing
efficacy; introducing mutations to disrupt either SL attenuated miR159 efficacy,
while introducing complementary mutations to restore the SLs, but not the
sequence, restored strong miR159-mediated silencing. Therefore, it appears that
this RNA secondary structure demarcates MYB33/65 as sensitive targets of miR159,
which underpins the narrow functional specificity of Arabidopsis miR159.
PMID- 28515147
TI - Increased T-cell Infiltration Elicited by Erk5 Deletion in a Pten-Deficient Mouse
Model of Prostate Carcinogenesis.
AB - Prostate cancer does not appear to respond to immune checkpoint therapies where T
cell infiltration may be a key limiting factor. Here, we report evidence that
ablating the growth regulatory kinase Erk5 can increase T-cell infiltration in an
established Pten-deficient mouse model of human prostate cancer. Mice that were
doubly mutant in prostate tissue for Pten and Erk5 (prostate DKO) exhibited a
markedly increased median survival with reduced tumor size and proliferation
compared with control Pten-mutant mice, the latter of which exhibited increased
Erk5 mRNA expression. A comparative transcriptomic analysis revealed upregulation
in prostate DKO mice of the chemokines Ccl5 and Cxcl10, two potent
chemoattractants for T lymphocytes. Consistent with this effect, we observed a
relative increase in a predominantly CD4+ T-cell infiltrate in the prostate
epithelial and stroma of tumors from DKO mice. Collectively, our results offer a
preclinical proof of concept for ERK5 as a target to enhance T-cell infiltrates
in prostate cancer, with possible implications for leveraging immune therapy in
this disease. Cancer Res; 77(12); 3158-68. (c)2017 AACR.
PMID- 28515148
TI - NEMO, a Transcriptional Target of Estrogen and Progesterone, Is Linked to Tumor
Suppressor PML in Breast Cancer.
AB - The beneficial versus detrimental roles of estrogen plus progesterone (E+P) in
breast cancer remains controversial. Here we report a beneficial mechanism of E+P
treatment in breast cancer cells driven by transcriptional upregulation of the
NFkappaB modulator NEMO, which in turn promotes expression of the tumor
suppressor protein promyelocytic leukemia (PML). E+P treatment of patient-derived
epithelial cells derived from ductal carcinoma in situ (DCIS) increased secretion
of the proinflammatory cytokine IL6. Mechanistic investigations indicated that
IL6 upregulation occurred as a result of transcriptional upregulation of NEMO,
the gene that harbored estrogen receptor (ER) binding sites within its promoter.
Accordingly, E+P treatment of breast cancer cells increased ER binding to the
NEMO promoter, thereby increasing NEMO expression, NFkappaB activation, and IL6
secretion. In two mouse xenograft models of DCIS, we found that RNAi-mediated
silencing of NEMO increased tumor invasion and progression. This seemingly
paradoxical result was linked to NEMO-mediated regulation of NFkappaB and IL6
secretion, increased phosphorylation of STAT3 on Ser727, and increased expression
of PML, a STAT3 transcriptional target. In identifying NEMO as a pivotal
transcriptional target of E+P signaling in breast cancer cells, our work offers a
mechanistic explanation for the paradoxical antitumorigenic roles of E+P in
breast cancer by showing how it upregulates the tumor suppressor protein PML.
Cancer Res; 77(14); 3802-13. (c)2017 AACR.
PMID- 28515146
TI - Transcriptome Profiling of Wheat Inflorescence Development from Spikelet
Initiation to Floral Patterning Identified Stage-Specific Regulatory Genes.
AB - Early reproductive development in cereals is crucial for final grain number per
spike and hence the yield potential of the crop. To date, however, no systematic
analyses of gene expression profiles during this important process have been
conducted for common wheat (Triticum aestivum). Here, we studied the
transcriptome profiles at four stages of early wheat reproductive development,
from spikelet initiation to floral organ differentiation. K-means clustering and
stage-specific transcript identification detected dynamically expressed homeologs
of important transcription regulators in spikelet and floral meristems that may
be involved in spikelet initiation, floret meristem specification, and floral
organ patterning, as inferred from their homologs in model plants. Small RNA
transcriptome sequencing discovered key microRNAs that were differentially
expressed during wheat inflorescence development alongside their target genes,
suggesting that miRNA-mediated regulatory mechanisms for floral development may
be conserved in cereals and Arabidopsis. Our analysis was further substantiated
by the functional characterization of the ARGONAUTE1d (AGO1d) gene, which was
initially expressed in stamen primordia and later in the tapetum during anther
maturation. In agreement with its stage-specific expression pattern, the loss of
function of the predominantly expressed B homeolog of AGO1d in a tetraploid durum
wheat mutant resulted in smaller anthers with more infertile pollens than the
wild type and a reduced grain number per spike. Together, our work provides a
first glimpse of the gene regulatory networks in wheat inflorescence development
that may be pivotal for floral and grain development, highlighting potential
targets for genetic manipulation to improve future wheat yields.
PMID- 28515149
TI - Pyruvate Kinase Inhibits Proliferation during Postnatal Cerebellar Neurogenesis
and Suppresses Medulloblastoma Formation.
AB - Aerobic glycolysis supports proliferation through unresolved mechanisms. We have
previously shown that aerobic glycolysis is required for the regulated
proliferation of cerebellar granule neuron progenitors (CGNP) and for the growth
of CGNP-derived medulloblastoma. Blocking the initiation of glycolysis via
deletion of hexokinase-2 (Hk2) disrupts CGNP proliferation and restricts
medulloblastoma growth. Here, we assessed whether disrupting pyruvate kinase-M
(Pkm), an enzyme that acts in the terminal steps of glycolysis, would alter CGNP
metabolism, proliferation, and tumorigenesis. We observed a dichotomous pattern
of PKM expression, in which postmitotic neurons throughout the brain expressed
the constitutively active PKM1 isoform, while neural progenitors and
medulloblastomas exclusively expressed the less active PKM2. Isoform-specific
Pkm2 deletion in CGNPs blocked all Pkm expression. Pkm2-deleted CGNPs showed
reduced lactate production and increased SHH-driven proliferation. 13C-flux
analysis showed that Pkm2 deletion reduced the flow of glucose carbons into
lactate and glutamate without markedly increasing glucose-to-ribose flux. Pkm2
deletion accelerated tumor formation in medulloblastoma-prone ND2:SmoA1 mice,
indicating the disrupting PKM releases CGNPs from a tumor-suppressive effect.
These findings show that distal and proximal disruptions of glycolysis have
opposite effects on proliferation, and that efforts to block the oncogenic effect
of aerobic glycolysis must target reactions upstream of PKM. Cancer Res; 77(12);
3217-30. (c)2017 AACR.
PMID- 28515151
TI - Assessing the satisfaction and burden within an academic animal care and use
program.
AB - Although animal research requires adherence to various regulations and standards,
the manner in which compliance is maintained and the degree of additional
constraints varies between institutions. Regulatory burden, particularly if
institutionally imposed, has become a concern for institutions as increased
regulatory expectations result in decreased resources available for research
efforts. Faculty, research staff, and support staff engaged in animal research
were surveyed to determine what institutional animal care and use committee
(IACUC) processes were considered burdensome, the perceived value of some
suggested modifications, and satisfaction with the IACUC administrative office
and the animal resource unit. Although the results revealed overwhelming
satisfaction with the IACUC administrative office and the animal resource unit,
several IACUC processes were deemed burdensome, and therefore there would be
value in modifying IACUC processes. When comparing the value of modifying IACUC
processes, different groups within the animal care and use program (ACUP) tended
to have different responses on many of the topics. This survey identified several
perceived burdensome IACUC processes that would likely benefit individuals if
modified. In today's environment of shrinking budgets for biomedical research,
minimizing regulatory burden-particularly unnecessary, self-imposed burden-in the
ACUP is particularly important to ensure that costs, time, and effort are
appropriate to achieve animal welfare and quality of research endeavors.-Norton,
J. N., Reynolds, R. P., Chan, C., Valdivia, R. H., Staats, H. F. Assessing the
satisfaction and burden within an academic animal care and use program.
PMID- 28515150
TI - Receptor for advanced glycation end products is targeted by FBXO10 for
ubiquitination and degradation.
AB - The receptor for advanced glycation end products (RAGE) is a highly expressed
cell membrane receptor serving to anchor lung epithelia to matrix components, and
it also amplifies inflammatory signaling during acute lung injury. However,
mechanisms that regulate its protein concentrations in cells remain largely
unknown. Here we show that RAGE exhibits an extended life span in lung epithelia
(t1/2 6 h), is monoubiquitinated at K374, and is degraded in lysosomes. The RAGE
ligand ODN2006, a synthetic oligodeoxynucleotide resembling pathogenic
hypomethylated CpG DNA, promotes rapid lysosomal RAGE degradation through
activation of protein kinase Czeta (PKCzeta), which phosphorylates RAGE. PKCzeta
overexpression enhances RAGE degradation, while PKCzeta knockdown stabilizes RAGE
protein levels and prevents ODN2006-mediated degradation. We identify that RAGE
is targeted by the ubiquitin E3 ligase subunit F-box protein O10 (FBXO10), which
associates with RAGE to mediate its ubiquitination and degradation. FBXO10
depletion in cells stabilizes RAGE and is required for ODN2006-mediated
degradation. These data suggest that modulation of regulators involved in
ubiquitin-mediated disposal of RAGE might serve as unique molecular inputs
directing RAGE cellular concentrations and downstream responses, which are
critical in an array of inflammatory disorders, including acute lung injury.
Evankovich, J., Lear, T., Mckelvey, A., Dunn, S., Londino, J., Liu, Y., Chen, B.
B., Mallampalli, R. K. Receptor for advanced glycation end products is targeted
by FBXO10 for ubiquitination and degradation.
PMID- 28515152
TI - Effects of deficiency of Kelch-like ECH-associated protein 1 on skeletal
organization: a mechanism for diminished nuclear factor of activated T cells
cytoplasmic 1 during osteoclastogenesis.
AB - Kelch-like ECH-associated protein 1 (Keap1) binds to nuclear factor E2 p45
related factor 2 (Nrf2), a transcription factor for antioxidant enzymes, to
suppress Nrf2 activation. The role of oxidative stress in many diseases supports
the possibility that processes that are associated with Nrf2 activation might
offer therapeutic potential. Nrf2 deficiency induces osteoclastogenesis, which is
responsible for bone loss, by activating receptor activator of NF-kappaB ligand
(RANKL)-mediated signaling; however, the effects of Keap1 deficiency remain
unclear. By using Keap1-deficient newborn mice, we observed that talus and
calcaneus bone formation was partially retarded and that osteoclast number was
reduced in vivo without severe gross abnormalities. In addition, Keap1-deficient
macrophages were unable to differentiate into osteoclasts in vitrovia attenuation
of RANKL-mediated signaling and expression of nuclear factor of activated T cells
cytoplasmic 1 (NFATc1), a key transcription factor that is involved in
osteoclastogenesis. Furthermore, Keap1 deficiency up-regulated the expression of
Mafb, a negative regulator of NFATc1. RANKL-induced mitochondrial gene expression
is required for down-regulation of IFN regulatory factor 8 (IRF-8), a negative
transcriptional regulator of NFATc1. Our results indicate that Keap1 deficiency
down-regulated peroxisome proliferator-activated receptor-gamma coactivator 1beta
and mitochondrial gene expression and up-regulated Irf8 expression. These results
suggest that the Keap1/Nrf2 axis plays a critical role in NFATc1 expression and
osteoclastogenic progression.-Sakai, E., Morita, M., Ohuchi, M., Kido, M. A.,
Fukuma, Y., Nishishita, K., Okamoto, K., Itoh, K., Yamamoto, M., Tsukuba, T.
Effects of deficiency of Kelch-like ECH-associated protein 1 on skeletal
organization: a mechanism for diminished nuclear factor of activated T cells
cytoplasmic 1 during osteoclastogenesis.
PMID- 28515153
TI - Differential regulation of renal Klotho and FGFR1 in normal and uremic rats.
AB - In renal failure, hyperphosphatemia occurs despite a marked elevation in serum
fibroblast growth factor (FGF)-23. Abnormal regulation of the FGFR1-Klotho
receptor complex may cause a resistance to the phosphaturic action of FGF23. The
purpose of the present study was to investigate the regulation of renal Klotho
and FGF receptor (FEFR)-1 in healthy and uremic rats induced by 5/6 nephrectomy.
In normal rats, the infusion of rat recombinant FGF23 enhanced phosphaturia and
increased renal FGFR1 expression; however, Klotho expression was reduced. Uremic
rats on a high-phosphate (HP) diet presented hyperphosphatemia with marked
elevation of FGF23 and an increased fractional excretion of phosphate (P) that
was associated with a marked reduction of Klotho expression and an increase in
FGFR1. After neutralization of FGF23 by anti-FGF23 administration, phosphaturia
was still abundant, Klotho expression remained low, and the FGFR1 level was
reduced. These results suggest that the expression of renal Klotho is modulated
by phosphaturia, whereas the FGFR1 expression is regulated by FGF23. Calcitriol
(CTR) administration prevented a decrease in renal Klotho expression. In HEK293
cells HP produced nuclear translocation of beta-catenin, together with a
reduction in Klotho. Wnt/beta-catenin inhibition with Dkk-1 prevented the P
induced down-regulation of Klotho. The addition of CTR to HP medium was able to
recover Klotho expression. In summary, high FGF23 levels increase FGFR1, whereas
phosphaturia decreases Klotho expression through the activation of Wnt/beta
catenin pathway.-Munoz-Castaneda, J. R., Herencia, C., Pendon-Ruiz de Mier, M.
V., Rodriguez-Ortiz, M. E., Diaz-Tocados, J. M., Vergara, N., Martinez-Moreno, J.
M., Salmeron, M. D., Richards, W. G., Felsenfeld, A., Kuro-O, M., Almaden, Y.,
Rodriguez, M. Differential regulation of renal Klotho and FGFR1 in normal and
uremic rats.
PMID- 28515155
TI - Building an Ideal Quality Metric for ESRD Health Care Delivery.
PMID- 28515154
TI - Progerin sequestration of PCNA promotes replication fork collapse and
mislocalization of XPA in laminopathy-related progeroid syndromes.
AB - Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder that is
caused by a point mutation in the LMNA gene, resulting in production of a
truncated farnesylated-prelamin A protein (progerin). We previously reported that
XPA mislocalized to the progerin-induced DNA double-strand break (DSB) sites,
blocking DSB repair, which led to DSB accumulation, DNA damage responses, and
early replication arrest in HGPS. In this study, the XPA mislocalization to DSBs
occurred at stalled or collapsed replication forks, concurrent with a significant
loss of PCNA at the forks, whereas PCNA efficiently bound to progerin. This PCNA
sequestration likely exposed ds-ssDNA junctions at replication forks for XPA
binding. Depletion of XPA or progerin each significantly restored PCNA at
replication forks. Our results suggest that although PCNA is much more
competitive than XPA in binding replication forks, PCNA sequestration by progerin
may shift the equilibrium to favor XPA binding. Furthermore, we demonstrated that
progerin-induced apoptosis could be rescued by XPA, suggesting that XPA
replication fork binding may prevent apoptosis in HGPS cells. Our results propose
a mechanism for progerin-induced genome instability and accelerated replicative
senescence in HGPS.-Hilton, B. A., Liu, J., Cartwright, B. M., Liu, Y., Breitman,
M., Wang, Y., Jones, R., Tang, H., Rusinol, A., Musich, P. R., Zou, Y. Progerin
sequestration of PCNA promotes replication fork collapse and mislocalization of
XPA in laminopathy-related progeroid syndromes.
PMID- 28515157
TI - Carboxyamidotriazole Synergizes with Sorafenib to Combat Non-Small Cell Lung
Cancer through Inhibition of NANOG and Aggravation of Apoptosis.
AB - Lung cancer is currently the leading cause of cancer-related deaths worldwide. In
this study, we investigated the combination of carboxyamidotriazole (CAI) and
sorafenib in non-small cell lung cancer (NSCLC) in vitro and in vivo to test
whether CAI enhances the antitumor effects of sorafenib and reduces its side
effects. The combination index (CI) showed that coadministration of CAI and
sorafenib synergistically inhibited the proliferation of NSCLC cells (Lewis lung
carcinoma, A549, and NCI-H1975 cells). Cell death as a result of the combination
treatment was attributed to apoptosis, which was accompanied by activation of
caspase-3 and poly(ADP-ribose) polymerase. In addition, combination therapy
induced the accumulation of mitochondrial-associated reactive oxygen species, as
well as depolarization of mitochondrial and reduced NANOG (homeobox protein
NANOG) mRNA and protein expression. Basic fibroblast growth factor, a stimulator
of NANOG, was applied to identify the possible mechanism. The addition of basic
fibroblast growth factor followed by combined treatment may stimulate NANOG
expression and synchronously rescue the accumulation of reactive oxygen species.
C57BL/6J mice bearing Lewis lung carcinoma were randomized to receive vehicle
(polyethylene glycol 400), CAI (30 mg/kg), low-dose sorafenib (SFB-L; 10 mg/kg),
high-dose sorafenib (SFB-H; 30 mg/kg), or a CAI and SFB-L combination. Tumor
growth was significantly suppressed in the combination group, and the efficacy of
combination treatment was equivalent to that of the SFB-H monotherapy group.
Furthermore, the combination group had reduced side effects compared with the SFB
H group, as indicated by weight preservation in mice. Our study illustrates that
CAI enhances the antitumor activity of sorafenib in NSCLC and provides a novel
strategy for NSCLC treatment.
PMID- 28515156
TI - Anti-Glomerular Basement Membrane Disease.
AB - Anti-glomerular basement membrane (anti-GBM) disease is a rare small vessel
vasculitis that affects the capillary beds of the kidneys and lungs. It is an
archetypic autoimmune disease, caused by the development of directly pathogenic
autoantibodies targeting a well characterized autoantigen expressed in the
basement membranes of these organs, although the inciting events that induce the
autoimmune response are not fully understood. The recent confirmation of spatial
and temporal clustering of cases suggests that environmental factors, including
infection, may trigger disease in genetically susceptible individuals. The
majority of patients develop widespread glomerular crescent formation, presenting
with features of rapidly progressive GN, and 40%-60% will have concurrent
alveolar hemorrhage. Treatment aims to rapidly remove pathogenic autoantibody,
typically with the use of plasma exchange, along with steroids and cytotoxic
therapy to prevent ongoing autoantibody production and tissue inflammation.
Retrospective cohort studies suggest that when this combination of treatment is
started early, the majority of patients will have good renal outcome, although
presentation with oligoanuria, a high proportion of glomerular crescents, or
kidney failure requiring dialysis augur badly for renal prognosis. Relapse and
recurrent disease after kidney transplantation are both uncommon, although de
novo anti-GBM disease after transplantation for Alport syndrome is a recognized
phenomenon. Copresentation with other kidney diseases such as ANCA-associated
vasculitis and membranous nephropathy seems to occur at a higher frequency than
would be expected by chance alone, and in addition atypical presentations of anti
GBM disease are increasingly reported. These observations highlight the need for
future work to further delineate the immunopathogenic mechanisms of anti-GBM
disease, and how to better refine and improve treatments, particularly for
patients presenting with adverse prognostic factors.
PMID- 28515158
TI - Anti-Psoriatic Drug Monomethylfumarate Increases Nuclear Factor Erythroid 2
Related Factor 2 Levels and Induces Aquaporin-3 mRNA and Protein Expression.
AB - Oxidative stress contributes to inflammatory skin diseases, including psoriasis.
Monomethylfumarate (MMF) is an antipsoriatic agent with a poorly understood
mechanism of action. In other cell types MMF increases the expression of nuclear
factor erythroid-derived 2-like 2 (Nrf2), a transcription factor that regulates
cellular antioxidant responses, to reduce oxidative stress like that observed in
inflammatory disorders such as multiple sclerosis. We tested the hypothesis that
MMF enhances Nrf2 activity in keratinocytes, thereby improving their capacity to
counteract environmental stresses. We used Western analysis, immunofluorescence,
and real-time quantitative reverse-transcription polymerase chain reaction to
examine the effect of MMF on the expression of Nrf2 and its targets. We also
measured intracellular reactive oxygen species (ROS) levels following MMF
treatment. Our data show that MMF increased total and nuclear Nrf2 levels in
primary mouse keratinocytes and enhanced mRNA expression of several Nrf2
downstream effectors, including heme oxygenase-1 and peroxiredoxin-6. Moreover,
MMF treatment attenuated the generation of ROS following hydrogen peroxide
treatment. On the other hand, the expression and membranous localization of
aquaporin-3 (AQP3), a glycerol channel implicated in keratinocyte
differentiation, was stimulated by MMF, which also enhanced keratinocyte glycerol
uptake. The Nrf2 activator sulforaphane also increased AQP3 levels, suggesting
that AQP3 expression may be regulated by Nrf2. We show for the first time that
MMF stimulates Nrf2 and AQP3 expression and function/activity in keratinocytes.
This effect may account, in part, for the previously observed ability of MMF to
inhibit proliferation and inflammatory mediator production and promote
differentiation in keratinocytes and to treat psoriasis.
PMID- 28515159
TI - Intermittent Fasting Pretreatment Prevents Cognitive Impairment in a Rat Model of
Chronic Cerebral Hypoperfusion.
AB - Background: Whether intermittent fasting (IF) pretreatment can prevent vascular
cognitive dysfunction remains unknown to our knowledge.Objective: We investigated
the effects and underlying mechanisms of IF pretreatment on cognitive dysfunction
in a permanent 2-vessel occlusion (2VO) vascular dementia rat model.Methods: Male
Wistar rats weighing 200 g were subjected to either IF or ad libitum feeding for
12 wk before 2VO surgery. Rats in the IF protocol underwent alternative-day feed
deprivation (FD). Memory of the animals was assessed by using the Morris water
maze (MWM) and the novel object recognition (NOR) test 6 wk after the surgery.
After behavioral testing, malondialdehyde and glutathione concentrations,
superoxide dismutase (SOD) activity, gene expression of antioxidative enzymes,
inflammatory protein concentrations, and microglia density were determined in the
hippocampus of rats.Results: 2-vessel occlusion operation ad libitum (2VO-AL)
rats had significantly longer escape latencies on day 4 of the training phase and
spent a lower percentage of time in the target quadrant (25% compared with 38%
and 41%) in the MWM, and had lower discrimination ratios (47% compared with 65%
and 67%) in the NOR test than 2-vessel operation and alternate-day feed
deprivation (2VO-FD) and sham operation ad libitum (Sham-AL) rats, respectively
(P < 0.05). This indicates that IF helps to prevent vascular cognitive deficits.
2VO-AL rats also had higher malondialdehyde (3.54 compared with 2.15 and 1.66
nmol/mg protein) and lower glutathione concentrations (53.25 compared with 66.41
and 91.71 nmol/mg protein), lower SOD activity (100.1 compared with 133.3 and
138.5 U/mg protein), lower gene expression of antioxidative enzymes, higher
expression of inflammatory proteins, and higher microglia density in the
hippocampus than 2VO-FD and Sham-AL rats, respectively (P < 0.05). This suggests
that IF has antioxidative and anti-inflammatory effects.Conclusions: IF
pretreatment provided sustained neuroprotection in a rat model of vascular
dementia. These effects were associated with reduced oxidative stress and
neuroinflammation.
PMID- 28515160
TI - Replacement of Refined Starches and Added Sugars with Egg Protein and Unsaturated
Fats Increases Insulin Sensitivity and Lowers Triglycerides in Overweight or
Obese Adults with Elevated Triglycerides.
AB - Background: Hypertriglyceridemia is a common condition in the United States and
is often associated with other metabolic disturbances, including insulin
resistance, metabolic syndrome, and a predominance of small dense LDL
particles.Objective: The objective of this trial was to evaluate the effects of a
combination of egg protein (Epro) and unsaturated fatty acids (UFAs) substituted
for refined starches and added sugars on insulin sensitivity (primary outcome)
and other cardiometabolic health markers in overweight or obese adults with
elevated triglyceride (TG) concentrations.Methods: Subjects with elevated TG
concentrations were given test foods prepared by using Epro powder (~8% of
energy) and vegetable oil (~8% of energy; Epro and UFA condition) or test foods
prepared by using refined starch and sugar (~16% of energy; carbohydrate
condition) in a randomized, double-blind, controlled-feeding, crossover trial (3
wk/condition, 2-wk washout). The Matsuda insulin sensitivity index (MISI),
fasting lipids, and other cardiometabolic health markers were assessed at
baseline and the end of each diet condition. Responses were compared by using
repeated-measures ANCOVA.Results: Twenty-five participants [11 men, 14 women;
mean +/- SEM: age, 46.3 +/- 2.4 y; body mass index (in kg/m2), 31.8 +/- 1.0] with
a median (interquartile range limits) fasting serum TG concentration of 173 mg/dL
(159, 228 mg/dL) completed the trial. The MISI value increased 18.1% +/- 8.7%
from baseline during the Epro and UFA condition and decreased 5.7% +/- 6.2% from
baseline during the carbohydrate condition (P < 0.001). The disposition index
increased 23.8% +/- 20.8% during the Epro and UFA condition compared with a
decrease of 16.3% +/- 18.8% during carbohydrate (P = 0.042) and LDL peak particle
size increased 0.12 nm (-0.12, 0.28 nm) with Epro and UFA compared with a
decrease of 0.15 nm (-0.33, 0.12 nm) with carbohydrate (P = 0.019). TG and VLDL
cholesterol concentrations were lowered by 18.5% (-35.7%, -6.9%) and 18.6% (
34.8%, -7.4%), respectively, after the Epro and UFA condition and by 2.5% (
13.4%, 17.0%) and 3.6% (-12.5%, 16.2%), respectively, after the carbohydrate diet
condition (P < 0.002).Conclusions: The replacement of refined carbohydrates with
a combination of Epro and UFA increased the MISI value and altered several
markers of cardiometabolic health in overweight or obese adults with elevated TG
concentrations. This trial was registered at clinicaltrials.gov as NCT02924558.
PMID- 28515161
TI - Suboptimal Maternal Iodine Intake Is Associated with Impaired Child
Neurodevelopment at 3 Years of Age in the Norwegian Mother and Child Cohort
Study.
AB - Background: Severe iodine deficiency in pregnancy has major effects on child
neurodevelopment, but less is known about the potential consequences of mild-to
moderate deficiency and iodine supplement use.Objective: We explored the
associations between maternal iodine intake and child neurodevelopment at 3 y of
age and the potential impact of maternal intake of iodine from supplements on the
same outcomes.Methods: This population-based prospective observational study
included 48,297 mother-child pairs recruited during pregnancy from 2002 to 2008.
Maternal iodine intake was calculated based on a validated food-frequency
questionnaire answered during midpregnancy that covered mean intake since the
beginning of pregnancy. Associations between iodine intake and maternal-reported
child language and motor development and behavior problems were explored by
multivariable regression analyses.Results: In 33,047 mother-child pairs,
excluding iodine supplement users, maternal iodine intake was associated with
child language delay (P = 0.024), externalizing and internalizing behavior
problems (both P < 0.001), and fine motor skills (P = 0.002) but not gross motor
skills or the risk of not walking unaided at 17 mo of age. In 74% of the
participants who had an iodine intake <160 MUg/d (Estimated Average Requirement),
suboptimal iodine intake was estimated to account for ~5% (95% CI: -5%, 14%) of
the cases of language delay, 16% (95% CI: 0%, 21%) of the cases of externalizing
behavior problems >1.5 SD, and 16% (95% CI: 10%, 21%) of the cases of
internalizing behavior problems >1.5 SD. In 48,297 mother-child pairs, including
iodine supplement users, we found no protective effects of supplemental iodine
during pregnancy on neurodevelopment.Conclusions: Maternal iodine intake below
the Estimated Average Requirement during pregnancy was associated with symptoms
of child language delay, behavior problems, and reduced fine motor skills at 3 y
of age. The results showed no evidence of a protective effect of iodine
supplementation during pregnancy.
PMID- 28515162
TI - Dietary Protein and the Health-Nutrition-Agriculture Connection in India.
AB - The connection between the production, availability, and consumption of high
quality food is becoming very important in developing countries. The requirement
of protein is linked to its quality, or its digestibility and ability to meet
human indispensable amino acid requirements. This requirement is particularly
relevant in India, where commonly consumed cereal-based diets and cereal-based
food subsidy programs offer low-quality protein and therefore pose a risk of
quality protein deficiency. The production of and access to sustainable sources
of high-quality protein will be important parts of mitigating risks to human
health. Although milk production has risen in India, its consumption by the poor
remains low. On the other hand, leguminous grain production, which has greater
climate resilience and soil improvement properties, has fallen, yet this can help
resource-poor farmers increase their intake of quality food. Nonetheless,
concerns about the nutritional quality of plant protein exist and may be more
relevant in settings where environmental enteric dysfunction already affects
nutrient absorption. With the use of nationally representative household protein
consumption data in India, the percentage of the population at risk of quality
protein deficiency was found to vary between 4% and 26% among different age
groups and between the urban or rural sector. Mitigating these risks requires a
greater intake of high-quality proteins, such as pulses and milk, and that food
subsidy policies move beyond cereals and become more quality conscious.
PMID- 28515163
TI - Assessment of Nitric Oxide Production in Mitochondrial Encephalomyopathy, Lactic
Acidosis, and Stroke-Like Episodes Syndrome with the Use of a Stable Isotope
Tracer Infusion Technique.
AB - Mitochondrial disorders result from dysfunctional mitochondria that are unable to
generate sufficient energy to meet the needs of various organs. Mitochondrial
encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is
one of the most frequent maternally inherited mitochondrial disorders. There is
growing evidence that nitric oxide (NO) deficiency occurs in MELAS syndrome and
results in impaired blood perfusion that contributes significantly to several
complications in this disease. NO is synthesized from arginine by NO synthase,
which catalyzes the conversion of arginine to NO and citrulline. Citrulline can
be recycled into arginine, and therefore, both arginine and citrulline support NO
synthesis. The use of 15N2-arginine and 13C-,2H4-citrulline stable isotope
infusion allows measuring arginine flux; citrulline flux; citrulline-to-arginine
flux, which represents the de novo arginine synthesis rate; and arginine-to
citrulline flux, which represents the NO production rate. The objective of this
review is to highlight the utility of this method in providing additional
evidence for NO deficiency in MELAS syndrome, adding more insight into the
potential mechanisms of NO deficiency in this syndrome, and allowing for the
assessment of the effects of supplementation with the NO donors, arginine and
citrulline, on improving NO production in MELAS syndrome.
PMID- 28515168
TI - The origin of the 'channel arrest' hypothesis.
PMID- 28515165
TI - Zinc Supplementation, via GPR39, Upregulates PKCzeta to Protect Intestinal
Barrier Integrity in Caco-2 Cells Challenged by Salmonella enterica Serovar
Typhimurium.
AB - Background: Zinc has been shown to improve intestinal barrier function against
Salmonella enterica serovar Typhimurium (S. typhimurium) infection, but the
mechanisms involved in this process remain undefined.Objective: We aimed to
explore the roles of G protein-coupled receptor (GPR)39 and protein kinase Czeta
(PKCzeta) in the regulation by zinc of intestinal barrier function.Methods: A
Transwell Caco-2 monolayer was pretreated with 0, 50, or 100 MUM Zn and then
incubated with S. typhimurium for 0-6 h. Afterward, cells silenced by the small
interfering RNA for GPR39 or PKCzeta were pretreated with 100 MUM Zn and
incubated with S. typhimurium for 3 h. Finally, transepithelial electrical
resistance (TEER), permeability, tight junction (TJ) proteins, and signaling
molecules GPR39 and PKCzeta were measured.Results: Compared with controls, S.
typhimurium decreased TEER by 62.3-96.2% at 4-6 h (P < 0.001), increased (P <
0.001) permeability at 6 h, and downregulated (P < 0.05) TJ protein zonula
occludens (ZO)-1 and occludin by 104-123%, as well as Toll-like receptor 2 and
PKCzeta by 35.1% and 75.2%, respectively. Compared with S. typhimurium-challenged
cells, 50 and 100 MUM Zn improved TEER by 26.3-60.9% at 4-6 h (P < 0.001) and
decreased (P < 0.001) permeability and bacterial invasion at 6 h. A total of 100
MUM Zn increased ZO-1, occludin, GPR39, and PKCzeta 0.72- to 1.34-fold (P <
0.05); however, 50 MUM Zn did not affect ZO-1 or occludin (P > 0.1). Silencing
GPR39 decreased (P < 0.05) zinc-activated PKCzeta and blocked (P < 0.05) the
promotion of zinc on epithelial integrity. Furthermore, silencing PKCzeta
counteracted the protective effect of zinc on epithelial integrity but did not
inhibit GPR39 (P = 0.138).Conclusion: We demonstrated that zinc upregulates
PKCzeta by activating GPR39 to enhance the abundance of ZO-1, thereby improving
epithelial integrity in S. typhimurium-infected Caco-2 cells.
PMID- 28515164
TI - mRNA Levels of Placental Iron and Zinc Transporter Genes Are Upregulated in
Gambian Women with Low Iron and Zinc Status.
AB - Background: The role of the placenta in regulating micronutrient transport in
response to maternal status is poorly understood.Objective: We investigated the
effect of prenatal nutritional supplementation on the regulation of placental
iron and zinc transport.Methods: In a randomized trial in rural Gambia [ENID
(Early Nutrition and Immune Development)], pregnant women were allocated to 1 of
4 nutritional intervention arms: 1) iron and folic acid (FeFol) tablets (FeFol
group); 2) multiple micronutrient (MMN) tablets (MMN group); 3) protein energy
(PE) as a lipid-based nutrient supplement (LNS; PE group); and 4) PE and MMN
(PE+MMN group) as LNS. All arms included iron (60 mg/d) and folic acid (400
MUg/d). The MMN and PE+MMN arms included 30 mg supplemental Zn/d. In a subgroup
of ~300 mother-infant pairs, we measured maternal iron status, mRNA levels of
genes encoding for placental iron and zinc transport proteins, and cord blood
iron levels.Results: Maternal plasma iron concentration in late pregnancy was 45%
and 78% lower in the PE and PE+MMN groups compared to the FeFol and MMN groups,
respectively (P < 0.001). The mRNA levels of the placental iron uptake protein
transferrin receptor 1 were 30-49% higher in the PE and PE+MMN arms than in the
FeFol arm (P < 0.031), and also higher in the PE+MMN arm (29%; P = 0.042) than in
the MMN arm. Ferritin in infant cord blood was 18-22% lower in the LNS groups (P
< 0.024). Zinc supplementation in the MMN arm was associated with higher maternal
plasma zinc concentrations (10% increase; P < 0.001) than in other intervention
arms. mRNA levels for intracellular zinc-uptake proteins, in this case zrt, irt
like protein (ZIP) 4 and ZIP8, were 96-205% lower in the PE+MMN arm than in the
intervention arms without added zinc (P < 0.025). Furthermore, mRNA expression of
ZIP1 was 85% lower in the PE+MMN group than in the PE group (P =
0.003).Conclusion: In conditions of low maternal iron and in the absence of
supplemental zinc, the placenta upregulates the gene expression of iron and zinc
uptake proteins, presumably in order to meet fetal demands in the face of low
maternal supply. The ENID trial was registered at www.controlled-trials.com as
ISRCTN49285450.
PMID- 28515169
TI - Osmoregulation, bioenergetics and oxidative stress in coastal marine
invertebrates: raising the questions for future research.
AB - Osmoregulation is by no means an energetically cheap process, and its costs have
been extensively quantified in terms of respiration and aerobic metabolism.
Common products of mitochondrial activity are reactive oxygen and nitrogen
species, which may cause oxidative stress by degrading key cell components, while
playing essential roles in cell homeostasis. Given the delicate equilibrium
between pro- and antioxidants in fueling acclimation responses, the need for a
thorough understanding of the relationship between salinity-induced oxidative
stress and osmoregulation arises as an important issue, especially in the context
of global changes and anthropogenic impacts on coastal habitats. This is
especially urgent for intertidal/estuarine organisms, which may be subject to
drastic salinity and habitat changes, leading to redox imbalance. How do
osmoregulation strategies determine energy expenditure, and how do these
processes affect organisms in terms of oxidative stress? What mechanisms are used
to cope with salinity-induced oxidative stress? This Commentary aims to highlight
the main gaps in our knowledge, covering all levels of organization. From an
energy-redox perspective, we discuss the link between environmental salinity
changes and physiological responses at different levels of biological
organization. Future studies should seek to provide a detailed understanding of
the relationship between osmoregulatory strategies and redox metabolism, thereby
informing conservation physiologists and allowing them to tackle the new
challenges imposed by global climate change.
PMID- 28515170
TI - Respiratory function and mechanics in pinnipeds and cetaceans.
AB - In this Review, we focus on the functional properties of the respiratory system
of pinnipeds and cetaceans, and briefly summarize the underlying anatomy; in
doing so, we provide an overview of what is currently known about their
respiratory physiology and mechanics. While exposure to high pressure is a common
challenge among breath-hold divers, there is a large variation in respiratory
anatomy, function and capacity between species - how are these traits adapted to
allow the animals to withstand the physiological challenges faced during dives?
The ultra-deep diving feats of some marine mammals defy our current understanding
of respiratory physiology and lung mechanics. These animals cope daily with lung
compression, alveolar collapse, transient hyperoxia and extreme hypoxia. By
improving our understanding of respiratory physiology under these conditions, we
will be better able to define the physiological constraints imposed on these
animals, and how these limitations may affect the survival of marine mammals in a
changing environment. Many of the respiratory traits to survive exposure to an
extreme environment may inspire novel treatments for a variety of respiratory
problems in humans.
PMID- 28515171
TI - Mutualistic damselfish induce higher photosynthetic rates in their host coral.
AB - Coral reefs are amongst the most diverse ecosystems on Earth where complex inter
specific interactions are ubiquitous. An example of such interactions is the
mutualistic relationship between damselfishes and branching corals in the
Northern Red Sea, where the fish use corals as shelter and provide them with
nutrients, enhance the flow between their branches, and protect them from
predators. By enhancing the flow between the coral branches, the fish ventilate
the coral's inner zone, mitigating hypoxic conditions that otherwise develop
within that zone during the night. Here, we tested, for the first time, the
effects of the damselfish Dascyllus marginatus on photosynthesis and respiration
in its host coral Stylophora pistillata Laboratory experiments using an
intermittent-flow respirometer showed that the presence of fish between the coral
branches under light conditions augmented the coral's photosynthetic rate. No
effect on the coral's respiration was found under dark conditions. When a fish
was allowed to enter the inner zone of a dead coral skeleton, its respiration was
higher than when it was in a live coral. Field observations indicated that
damselfish were present between coral branches 18-34% of the time during daylight
hours and at all times during the night. Considering the changes induced by the
fish together with the proportion of time they were found between coral branches
in the field, the effect of the fish amounted to an augmentation of 3-6% of the
coral's daily photosynthesis. Our findings reveal a previously unknown positive
contribution of coral-dwelling fish to their host's photosynthesis.
PMID- 28515173
TI - Heme oxygenase-1 mitigates ferroptosis in renal proximal tubule cells.
AB - Ferroptosis is an iron-dependent form of regulated nonapoptotic cell death, which
contributes to damage in models of acute kidney injury (AKI). Heme oxygenase-1
(HO-1) is a cytoprotective enzyme induced in response to cellular stress, and is
protective against AKI because of its antiapoptotic and anti-inflammatory
properties. However, the role of HO-1 in regulating ferroptosis is unclear. The
purpose of this study was to elucidate the role of HO-1 in regulating ferroptotic
cell death in renal proximal tubule cells (PTCs). Immortalized PTCs obtained from
HO-1+/+ and HO-1-/- mice were treated with erastin or RSL3, ferroptosis inducers,
in the presence or absence of antioxidants, an iron source, or an iron chelator.
Cells were assessed for changes in morphology and metabolic activity as an
indicator of cell viability. Treatment of HO-1+/+ PTCs with erastin resulted in a
time- and dose-dependent increase in HO-1 gene expression and protein levels
compared with vehicle-treated controls. HO-1-/- cells showed increased dose
dependent erastin- or RSL3-induced cell death in comparison to HO-1+/+ PTCs. Iron
supplementation with ferric ammonium citrate in erastin-treated cells decreased
cell viability further in HO-1-/- PTCs compared with HO-1+/+ cells. Cotreatment
with ferrostatin-1 (ferroptosis inhibitor), deferoxamine (iron chelator), or N
acetyl-l-cysteine (glutathione replenisher) significantly increased cell
viability and attenuated erastin-induced ferroptosis in both HO-1+/+ and HO-1-/-
PTCs. These results demonstrate an important antiferroptotic role of HO-1 in
renal epithelial cells.
PMID- 28515174
TI - Functional assessment of sodium chloride cotransporter NCC mutants in polarized
mammalian epithelial cells.
AB - The thiazide-sensitive sodium chloride cotransporter NCC is important for
maintaining serum sodium (Na+) and, indirectly, serum potassium (K+) levels.
Functional studies on NCC have used cell lines with native NCC expression,
transiently transfected nonpolarized cell lines, or Xenopus laevis oocytes. Here,
we developed the use of polarized Madin-Darby canine kidney type I (MDCKI)
mammalian epithelial cell lines with tetracycline-inducible human NCC expression
to study NCC activity and membrane abundance in the same system. In radiotracer
assays, induced cells grown on filters had robust thiazide-sensitive and chloride
dependent sodium-22 (22Na) uptake from the apical side. To minimize cost and
maximize throughput, assays were modified to use cells grown on plastic. On
plastic, cells had similar thiazide-sensitive 22Na uptakes that increased
following preincubation of cells in chloride-free solutions. NCC was detected in
the plasma membrane, and both membrane abundance and phosphorylation of NCC were
increased by incubation in chloride-free solutions. Furthermore, in cells exposed
for 15 min to low or high extracellular K+, the levels of phosphorylated NCC
increased and decreased, respectively. To demonstrate that the system allows
rapid and systematic assessment of mutated NCC, three phosphorylation sites in
NCC were mutated, and NCC activity was examined. 22Na fluxes in phosphorylation
deficient mutants were reduced to baseline levels, whereas phosphorylation
mimicking mutants were constitutively active, even without chloride-free
stimulation. In conclusion, this system allows the activity, cellular
localization, and abundance of wild-type or mutant NCC to be examined in the same
polarized mammalian expression system in a rapid, easy, and low-cost fashion.
PMID- 28515172
TI - Cross-sex transplantation alters gene expression and enhances inflammatory
response in the transplanted kidneys.
AB - Kidney transplantation (KTX) is a life-saving procedure for patients with end
stage renal disease. Expression levels of many genes in the kidney vary between
males and females, which may play an essential role in the sex differences in
graft function. However, whether these differences are affected after cross-sex
KTX is unknown. In the present study, we assessed postoperative changes in
genotype, function, and inflammatory responses of the grafts in same-sex- and
cross-sex-KTX. Single kidney transplants were performed between same and
different sex C57BL/6 mice paired into four combination groups: female
donor/female recipient (F/F); male donor/male recipient (M/M); female donor/male
recipient (F/M); and male donor/female recipient (M/F). The remnant native kidney
was removed 4 days posttransplant. Expression levels of genes related to the
contractility of the afferent arteriole and tubular sodium reabsorption were
assessed. Same-sex-KTX did not significantly alter the magnitude or sex
difference pattern of gene expression in male or female grafts. Cross-sex-KTX
showed an attenuated sex difference in gene expressions. The measurements of
endothelin 1, endothelin ETA receptor, Na+-K--2Cl cotransporter 2 (NKCC2), and
epithelial Na+ channels (ENaC) subunits exhibited decreases in M/F compared with
M/M and increases in F/M compared with F/F. There were no significant differences
in hemodynamics or sodium excretion in response to acute volume expansion for any
sex combinations. Cross-sex-KTX stimulated more robust inflammatory responses
than same-sex-KTX. IL-6 and KC mRNA levels elevated 5- to 20-fold in cross-sex
KTX compared with same-sex-KTX. In conclusion, cross-sex-KTX alters gene
expression levels and induces inflammatory responses, which might play an
important role in long-term graft function.
PMID- 28515175
TI - Role for reactive oxygen species in flow-stimulated inner medullary collecting
duct endothelin-1 production.
AB - Inner medullary collecting duct (IMCD)-derived endothelin-1 (ET-1) is stimulated
by volume expansion, in part through augmented luminal flow, whereupon it can
elicit natriuresis and diuresis. Since flow can alter nitric oxide (NO) and
reactive oxygen species (ROS), both of which can affect collecting duct salt
transport, we asked whether NO and/or ROS mediate flow-stimulated IMCD ET-1.
Mouse IMCD3 cells were exposed to flow, and ET-1/GAPDH mRNA was assessed. A shear
stress of 10 dyn/cm2 for 1 h increased ET-1 mRNA by fourfold compared with no
flow (ET-1 flow response). Global NO synthase (NOS) inhibition [NG-nitro-l
arginine methyl ester (l-NAME)] reduced the ET-1 flow response; however,
pharmacological inhibition of NOS1 or NOS2, inhibition of NOS3 siRNA, inhibition
of arginase inhibition, removal of media l-Arg, or inhibition of NO-dependent
signaling pathways (PKG, guanylyl cyclase, or NF-kappaB) did not affect the ET-1
flow response. Tempol reduced the ET-1 flow response; no further inhibition
occurred with l-NAME. Superoxide dismutase, but not catalase, reduced the ET-1
flow response. Inhibition of NAPDH oxidase (NOX) (apocynin), pharmacological
inhibition of NOX1/4, or NOX4 siRNA reduced the ET-1 flow response. Finally, flow
increased IMCD3 ROS production and this was inhibited by apocynin, NOX1/4
inhibition, and, to a small extent, by l-NAME. Taken together, these data suggest
that NOX4-derived ROS in general, and possibly superoxide in particular, are
involved in flow-stimulated IMCD ET-1 production. To our knowledge, this is the
first report of flow-stimulated ROS production by the CD, as well as the first
report of such flow-stimulated CD ROS exerting a biological effect.
PMID- 28515177
TI - Do beta3-adrenoceptor agonists cause urinary bladder smooth muscle relaxation by
inhibiting acetylcholine release?
PMID- 28515176
TI - Acute exercise does not impair renal function in nondialysis chronic kidney
disease patients regardless of disease stage.
AB - Exercise has been overlooked as a potential therapy in chronic kidney disease
(CKD), mainly because of a lack of understanding on its safety aspects. Notably,
there are no data on renal function after exercise in CKD considering its stages.
We investigated the acute effects of a 30-min moderate-intensity aerobic exercise
bout on glomerular filtration rate (GFR) and albuminuria in 22 nondialysis CKD
patients divided into: CKD stages 1 and 2 (CKD1-2) and CKD stages 3 and 4 (CKD3
4). Eleven body mass index-, age-, and sex-matched healthy individuals served as
control (CON). Blood and urine samples were collected before, immediately after,
and up to 90 min postexercise for creatinine and albumin assessments. GFR was
determined by creatinine clearance (GFRCr-Cl). All CKD patients had significantly
lower peak oxygen uptake than CON. CKD1-2 and CKD3-4 had increasingly higher
serum creatinine than CON (9.6 +/- 2.6, 25.6 +/- 1.01, and 7.5 +/- 1.4 mg/l,
respectively); however, no within-group changes in serum or urinary creatinine
were observed across time. GFRCr-Cl was decreased in CKD1-2 and CKD3-4 compared
with CON (91 +/- 17 ml.min-1.1.73 m-2; 34 +/- 15 ml.min-1.1.73 m-2; 122 +/- 20
ml.min-1.1.73 m-2, respectively). Most importantly, exercise did not affect GFRCr
Cl in none of the groups across time. Albuminuria was significantly higher in
CKD3-4 (297 +/- 284 ug/min) than in CON (5.4 +/- 1.4 ug/min), but no within-group
changes were observed after exercise. In conclusion, a single 30-min moderate
intensity aerobic exercise bout does not impair renal function in nondialysis CKD
patients, regardless of disease stage, supporting the notion that exercise
training can be safe in this disease.
PMID- 28515178
TI - A model-specific role of microRNA-223 as a mediator of kidney injury during
experimental sepsis.
AB - Sepsis outcomes are heavily dependent on the development of septic organ injury,
but no interventions exist to interrupt or reverse this process. microRNA-223
(miR-223) is known to be involved in both inflammatory gene regulation and host
pathogen interactions key to the pathogenesis of sepsis. The goal of this study
was to determine the role of miR-223 as a mediator of septic kidney injury. Using
miR-223 knockout mice and multiple models of experimental sepsis, we found that
miR-223 differentially influences acute kidney injury (AKI) based on the model
used. In the absence of miR-223, mice demonstrated exaggerated AKI in sterile
models of sepsis (LPS injection) and attenuated AKI in a live-infection model of
sepsis (cecal ligation and puncture). We demonstrated that miR-223 expression is
induced in kidney homogenate after cecal ligation and puncture, but not after LPS
or fecal slurry injection. We investigated additional potential mechanistic
explanations including differences in peritoneal bacterial clearance and host
stool virulence. Our findings highlight the complex role of miR-223 in the
pathogenesis of septic kidney injury, as well as the importance of differences in
experimental sepsis models and their consequent translational applicability.
PMID- 28515180
TI - Distribution and extent of electronic medical record utilisation in eye units
across the United Kingdom: a cross-sectional study of the current landscape.
AB - OBJECTIVES: Ophthalmology units across the UK vary widely in their adoption of
electronic medical records (EMR). There is a lack of evidence to show the extent
and progress of EMR adoption. The aim of this study was to capture a snapshot of
the current landscape of EMR use, as a baseline for comparison in future studies.
SETTING: An electronic survey questionnaire was sent to all NHS ophthalmology
Units in the UK. PARTICIPANTS: A total of 104 National Health Service (NHS)
ophthalmology units participated in the survey, which was carried out over 6
months from December 2013 to June 2014. PRIMARY AND SECONDARY OUTCOME MEASURES:
Respondents were asked about technology usage pertaining to specific processes in
the clinic workflow. This allowed us to determine the extent of EMR usage and
details about current use or planned implementation by each unit. RESULTS: 77.6%
(n=104) of NHS ophthalmology units responded. 45.3% (n=48) of units were
currently using an EMR and a further 26.4% (n=28) of units plan to implement EMR
within 2 years. 70.8% of units with a current EMR system use Medisoft. EMR is
used by all clinicians in 37.5% and by all subspecialties offered at the unit in
27.0%. In 56.3%, new clinical notes are entered into EMR only by clinicians. All
imaging devices are networked to EMR in 28.3%. In 46.7%, EMR is accessible by
other specialties within the same hospital. 71.1% would recommend EMR to a
colleague. CONCLUSIONS: EMR has the potential to address current limitations of
patient information transfer and sharing in ophthalmology. It is pleasing to see
a significant proportion of units already engaging with EMR or having plans to do
so in the near future. However, differing EMR systems and lack of remote access
mean further optimisation of these record systems are needed to allow data
transfer between units.
PMID- 28515181
TI - Measuring ability to assess claims about treatment effects: the development of
the 'Claim Evaluation Tools'.
AB - OBJECTIVES: To describe the development of the Claim Evaluation Tools, a set of
flexible items to measure people's ability to assess claims about treatment
effects. SETTING: Methodologists and members of the community (including
children) in Uganda, Rwanda, Kenya, Norway, the UK and Australia. PARTICIPANTS:
In the iterative development of the items, we used purposeful sampling of people
with training in research methodology, such as teachers of evidence-based
medicine, as well as patients and members of the public from low-income and high
income countries. Development consisted of 4 processes: (1) determining the scope
of the Claim Evaluation Tools and development of items; (2) expert item review
and feedback (n=63); (3) cognitive interviews with children and adult end-users
(n=109); and (4) piloting and administrative tests (n=956). RESULTS: The Claim
Evaluation Tools database currently includes a battery of multiple-choice items.
Each item begins with a scenario which is intended to be relevant across
contexts, and which can be used for children (from age 10 and above), adult
members of the public and health professionals. People with expertise in research
methods judged the items to have face validity, and end-users judged them
relevant and acceptable in their settings. In response to feedback from
methodologists and end-users, we simplified some text, explained terms where
needed, and redesigned formats and instructions. CONCLUSIONS: The Claim
Evaluation Tools database is a flexible resource from which researchers, teachers
and others can design measurement instruments to meet their own requirements.
These evaluation tools are being managed and made freely available for non
commercial use (on request) through Testing Treatments interactive
(testingtreatments.org). TRIAL REGISTRATION NUMBERS: PACTR201606001679337 and
PACTR201606001676150; Pre-results.
PMID- 28515179
TI - Arginase-2 mediates renal ischemia-reperfusion injury.
AB - Novel therapeutic interventions for preventing or attenuating kidney injury
following ischemia-reperfusion injury (IRI) remain a focus of significant
interest. Currently, there are no definitive therapeutic or preventive approaches
available for ischemic acute kidney injury (AKI). Our objective is to determine
1) whether renal arginase activity or expression is increased in renal IRI, and
2) whether arginase plays a role in development of renal IRI. The impact of
arginase activity and expression on renal damage was evaluated in male C57BL/6J
(wild type) and arginase-2 (ARG2)-deficient (Arg2-/- ) mice subjected to
bilateral renal ischemia for 28 min, followed by reperfusion for 24 h. ARG2
expression and arginase activity significantly increased following renal IRI,
paralleling the increase in kidney injury. Pharmacological blockade or genetic
deficiency of Arg2 conferred kidney protection in renal IRI. Arg2-/- mice had
significantly attenuated kidney injury and lower plasma creatinine and blood urea
nitrogen levels after renal IRI. Blocking arginases using S-(2-boronoethyl)-l
cysteine (BEC) 18 h before ischemia mimicked arginase deficiency by reducing
kidney injury, histopathological changes and kidney injury marker-1 expression,
renal apoptosis, kidney inflammatory cell recruitment and inflammatory cytokines,
and kidney oxidative stress; increasing kidney nitric oxide (NO) production and
endothelial NO synthase (eNOS) phosphorylation, kidney peroxisome proliferator
activated receptor-gamma coactivator-1alpha expression, and mitochondrial ATP;
and preserving kidney mitochondrial ultrastructure compared with vehicle-treated
IRI mice. Importantly, BEC-treated eNOS-knockout mice failed to reduce blood urea
nitrogen and creatinine following renal IRI. These findings indicate that ARG2
plays a major role in renal IRI, via an eNOS-dependent mechanism, and that
blocking ARG2 activity or expression could be a novel therapeutic approach for
prevention of AKI.
PMID- 28515182
TI - Health assets in older age: a systematic review.
AB - BACKGROUND: Finding ways to optimise health in older age is key to reducing the
impact of population ageing on health and social care systems. A salutogenic
approach takes into account an individual's health assets-internal or external
strengths or accessible resources which improve and preserve physical, social and
mental wellness, independence and quality of life. The aim of this narrative
systematic review was to provide a summary and appraisal of the evidence for
factors that act as health assets within personal, social, economic and
environmental domains. METHODS: Systematic searches of databases were conducted
for literature published in peer-reviewed journals between January 2000 and
November 2016. Selection criteria included community dwelling populations aged 65
years and over and publications written in English. Data on study population,
design, measures of health status, factors within the four previously stated
domains and results were extracted. Study quality was independently assessed
using an appraisal instrument. RESULTS: Twenty-three publications, including 78
422 participants, from more than 13 different countries were identified for
inclusion in this review. There was strong evidence that higher scores of self
rated health, psychological well-being and life satisfaction were associated with
better health in older age. Social network and contact with family and friends,
and engagement in leisure and social activities were important support
mechanisms. Education and financial resources consistently proved to be key
economic health assets for older adults. CONCLUSIONS: Implementing an asset-based
approach to health promotion uncovers the skills, knowledge, connections and
potential of the individual and the community. This approach is an ideal
opportunity for government health bodies and their partners to respond to the
challenges faced by global ageing.Factors are often interdependent and
cumulative, suggesting the potential for an instrument to measure the accumulated
effect of health assets on health status in older adults.
PMID- 28515183
TI - Modeling lifetime costs and health outcomes attributable to secondhand smoke
exposure at home among Korean adult women.
AB - PURPOSE: The aim of this research is to estimate lifetime costs and health
consequences for Korean adult women who were exposed to secondhand smoke (SHS) at
home. METHODS: A Markov model was developed to project the lifetime healthcare
costs and health outcomes of a hypothetical cohort of Korean women who are 40
years old and were married to current smokers. The Korean epidemiological data
were used to reflect the natural history of SHS-exposed and non-exposed women.
The direct healthcare costs (in 2014 US dollars) and quality-adjusted life years
(QALYs) were annually discounted at 5% to reflect time preference. The time
horizon of the analysis was lifetime and the cycle length was 1 year.
Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: In
the absence of SHS exposure, Korean women will live 41.32 years or 34.56 QALYs
before discount, which corresponded to 17.29 years or 15.35 QALYs after discount.
The SHS-exposed women were predicted to live 37.91 years and 31.08 QALYs before
discount and 16.76 years and 14.62 QALYs after discount. The estimated lifetime
healthcare cost per woman in the SHS non-exposed group was US$11 214 before the
discount and US$2465 after discount. The negative impact of SHS exposure on
health outcomes and healthcare costs escalated as the time horizon increased,
suggesting that the adverse impact of SHS exposure may have higher impact on the
later part of the lifetime. The result was consistent across a wide range of
assumptions. CONCLUSION: Life expectancy might underestimate the impact of SHS
exposure on health outcomes, especially if the time horizon of the analysis is
not long enough. Early intervention on smoking behaviour could substantially
reduce direct healthcare costs and improve quality of life attributable to SHS
exposure.
PMID- 28515184
TI - Trends and population-attributable risk estimates for predictors of early
neonatal mortality in Nigeria, 2003-2013: a cross-sectional analysis.
AB - OBJECTIVES: To assess trends in early neonatal mortality (ENM) and population
attributable risk (PAR) estimates for predictors of ENM in Nigeria. DESIGN,
SETTING AND PARTICIPANTS: A cross-sectional data on 63 844 singleton live births
within the preceding 5 years from the 2003, 2008 and 2013 Nigeria Demographic and
Health Surveys were used. Adjusted PARs were used to estimate the number of early
neonatal deaths attributable to each predictor in the final multivariable Cox
regression model. MAIN OUTCOME MEASURES: ENM, defined as the death of a live-born
singleton between birth and 6 days of life. RESULTS: The ENM rate slightly
declined from 30.5 (95% CI 26.1 to 34.9) to 26.1 (CI 24.3 to 27.9) during the
study period. Approximately 36 746 (CI 14 656 to 56 920) and 37 752 (CI 23 433 to
51 126) early neonatal deaths were attributable to rural residence and male sex,
respectively. Other significant predictors of ENM included small neonates
(attributable number: 25 884, CI 19 172 to 31 953), maternal age <20 years (11
708, CI 8521 to 17 042), caesarean section (6312, CI 4260 to 8521) and birth
order >=4 with a short birth interval (<=2 years) (18 929, CI 12 781 to 25 563)).
CONCLUSIONS: To improve early neonatal survival in Nigeria, community-based
interventions are needed for small neonates, and to promote delayed first
pregnancy, child spacing and timely referral for sick male neonates and caesarean
delivery.
PMID- 28515185
TI - The job content questionnaire in various occupational contexts: applying a latent
class model.
AB - OBJECTIVE: To evaluate Job Content Questionnaire(JCQ) performance using the
latent class model. METHODS: We analysed cross-sectional studies conducted in
Brazil and examined three occupational categories: petroleum industry workers
(n=489), teachers (n=4392) and primary healthcare workers (3078)and 1552 urban
workers from a representative sample of the city of Feira de Santana in Bahia,
Brazil. An appropriate number of latent classes was extracted and described each
occupational category using latent class analysis, a multivariate method that
evaluates constructs and takes into accountthe latent characteristics underlying
the structure of measurement scales. The conditional probabilities of workers
belonging to each class were then analysed graphically. RESULTS: Initially, the
latent class analysis extracted four classes corresponding to the four job types
(active, passive, low strain and high strain) proposed by the Job-Strain model
(JSM) and operationalised by the JCQ. However, after taking into consideration
the adequacy criteria to evaluate the number of extracted classes, three classes
(active, low strain and high strain) were extracted from the studies of urban
workers and teachers and four classes (active, passive, low strain and high
strain) from the study of primary healthcare and petroleum industry workers.
CONCLUSION: The four job types proposed by the JSM were identified among primary
healthcare and petroleum industry workers-groups with relatively high levels of
skill discretion and decision authority. Three job types were identified for
teachers and urban workers; however, passive job situations were not found within
these groups. The latent class analysis enabled us to describe the conditional
standard responses of the job types proposed by the model, particularly in
relation to active jobs and high and low strain situations.
PMID- 28515186
TI - Understanding determinants of unequal distribution of stillbirth in Tehran, Iran:
a concentration index decomposition approach.
AB - OBJECTIVE: The present inquiry set to determine the economic inequality in
history of stillbirth and understanding determinants of unequal distribution of
stillbirth in Tehran, Iran. METHODS: A population-based cross-sectional study was
conducted on 5170 pregnancies in Tehran, Iran, since 2015. Principal component
analysis (PCA) was applied to measure the asset-based economic status.
Concentration index was used to measure socioeconomic inequality in stillbirth
and then decomposed into its determinants. RESULTS: The concentration index and
its 95% CI for stillbirth was -0.121 (-0.235 to -0.002). Decomposition of the
concentration index showed that mother's education (50%), mother's occupation
(30%), economic status (26%) and father's age (12%) had the highest positive
contributions to measured inequality in stillbirth history in Tehran. Mother's
age (17%) had the highest negative contribution to inequality. CONCLUSIONS:
Stillbirth is unequally distributed among Iranian women and is mostly
concentrated among low economic status people. Mother-related factors had the
highest positive and negative contributions to inequality, highlighting specific
interventions for mothers to redress inequality.
PMID- 28515188
TI - Trends in socioeconomic inequalities in five major risk factors for
cardiovascular disease in the Korean population: a cross-sectional study using
data from the Korea National Health and Nutrition Examination Survey, 2001-2014.
AB - OBJECTIVES: To examine trends in socioeconomic inequalities in major
cardiovascular disease (CVD) risk factors among the Korean population. DESIGN:
Cross-sectional study. SETTING: A nationally representative population survey
database. PARTICIPANTS: A total of 42 725 Koreans, aged 25-64 years, who
participated in the Korean National Health and Nutrition Examination Survey
(KNHANES) II (2001) to VI (2013-2014). MAIN OUTCOME MEASURES: Trends in
socioeconomic inequalities in five major CVD risk factors (smoking, obesity,
diabetes, hypertension and hypercholesterolaemia). RESULTS: Gender differences
were noted in the time trends in socioeconomic inequalities in smoking, obesity,
diabetes and hypertension. Among men, low socioeconomic status (SES) was
associated with higher prevalence of smoking, but not with obesity, diabetes or
hypertension. The magnitudes of socioeconomic inequalities in smoking, obesity
and diabetes remained unchanged, and the magnitude of the inequality in
hypertension decreased over time. However, among women, low SES was associated
with higher prevalence of smoking, obesity, diabetes and hypertension. Time
trends towards increasing socioeconomic inequalities, measured by income, in
smoking, obesity and diabetes were found in women. Unlike the other CVD risk
factors, hypercholesterolaemia was not associated with socioeconomic inequality.
CONCLUSIONS: SES had a stronger impact on major CVD risk factors among Korean
women than men. Moreover, socioeconomic inequalities in smoking, obesity and
diabetes worsened among Korean women over time. Public policies to prevent
smoking, obesity and diabetes in women with lower SES are needed to address
inequalities.
PMID- 28515187
TI - Reducing social isolation and loneliness in older people: a systematic review
protocol.
AB - INTRODUCTION: Social isolation and loneliness affect approximately one-third to
one-half of the elderly population and have a negative impact on their physical
and mental health. Group-based interventions where facilitators are well trained
and where the elderly are actively engaged in their development seem to be more
effective, but conclusions have been limited by weak study designs. We aim to
conduct a systematic review to assess the effectiveness of health promotion
interventions on social isolation or loneliness in older people. METHODS AND
ANALYSIS: A systematic review was conducted in Medline, Embase, PsycINFO,
Cumulative Index to Nursing and Allied Health Literature, Applied Social Sciences
Index and Abstracts, LILACS, OpenGrey and the Cochrane Library on peer-reviewed
studies and doctoral theses published between 1995 and 2016 evaluating the impact
of health promotion interventions on social isolation and/or loneliness for
individuals aged 60 and over. Two reviewers will independently assess each study
for inclusion and disagreements will be resolved by a third reviewer. Data will
be extracted using a predefined pro forma following best practice. Study quality
will be assessed with the Effective Public Health Practice Project quality
assessment tool. A narrative synthesis of all studies will be presented by type
of outcome (social isolation or loneliness) and type of intervention. If
feasible, the effectiveness data will be synthesised using appropriate
statistical techniques. ETHICS AND DISSEMINATION: This systematic review is
exempt from ethics approval because the work is carried out on published
documents. The findings of the review will be disseminated in a related peer
reviewed journal and presented at conferences. They will also contribute to a
DPhil thesis. TRIAL REGISTRATION NUMBER: CRD42016039650.
PMID- 28515189
TI - 10-year trends in statin utilization in Taiwan: a retrospective study using
Taiwan's National Health Insurance Research Database.
AB - OBJECTIVE: Statins have been commonly used to treat patients with
hypercholesterolaemia and to prevent cardiovascular disease (CVD) worldwide. This
study examined trends in use of statins in Taiwan from 2002 to 2011. DESIGN: This
is a retrospective observational study focusing on the utilisation of statins.
SETTING: The monthly claims data for statins between 2002 and 2011 were retrieved
from Taiwan's National Health Insurance Research Database. MAIN OUTCOME MEASURES:
We calculated the yearly prescription rate per new user for each statin. Products
were classified as high-intensity/moderate-intensity/low-intensity statins by
type of statin and dosage. Users were also classified based on disease histories.
RESULTS: The number of statin users increased from 10 299 (~1.4% of adults) in
2002 to 50 687 (~6.3% of adults) in 2011. Atorvastatin was the most commonly used
agent (28.4%-36.7%) during the study period. After 2007, simvastatin ranked
second with 21.7% market share, followed by rosuvastatin, a newer agent that
exhibited a substantial growth in prescription rates (3.4% in 2005 and 19.5% in
2011). In 2011, 94.0% of new statin users used statin monotherapies, and 6.0%
used combination therapies. Use of moderate-intensity statins increased from
49.0% in 2002 to 71.0% in 2011, while high-intensity statins remained low.
Patients with history of coronary events or cerebrovascular events were more
likely to be prescribed higher intensity statins compared with those without.
Prescribing of higher intensity statins was not greater among people with
diabetes compared with those without during 2007-2011. Selection of statins did
not differ between people with versus without history of myopathy or liver
injury. CONCLUSION: Atorvastatin was the most commonly used statin in Taiwan
during 2002-2011. While patients with history of CVD were more likely to be
prescribed higher intensity statins compared with those without, this difference
was not found comparing those with and without diabetes.
PMID- 28515191
TI - Socially disparate trends in lifespan variation: a trend study on income and
mortality based on nationwide Danish register data.
AB - BACKGROUND: Social inequality trends in life expectancy are not informative as to
changes in social disparity in the age-at-death distribution. The purpose of the
study was to investigate social differentials in trends and patterns of adult
mortality in Denmark. METHODS: Register data on income and mortality from 1986 to
2014 were used to investigate trends in life expectancy, life disparity and the
threshold age that separates 'premature' and 'late' deaths. Mortality compression
was quantified and compared between income quartiles. RESULTS: Since 1986, male
life expectancy increased by 4.2 years for the lowest income quartile and by 8.4
years for the highest income quartile. The clear compression of mortality
apparent in the highest income quartile did not occur for the lowest income
quartile. Premature and late deaths accounted both by 2.1 years of the increase
in life expectancy in the lowest income quartile and by 6.0 and 2.4 years,
respectively, in the highest income quartile. Life expectancy increased by 5.2
years among women in the lowest income quartile, 2.4 years due to premature
deaths and 2.8 years due to late deaths. The gain in life expectancy among women
in the highest income quartile of 5.6 years was distributed by 5.0 and 0.6 years
due to premature and late deaths, respectively. CONCLUSION: The study
demonstrates that the increasing social gap in mortality appears differently in
the change of the age-at-death distribution. Thus, no compression of mortality
was seen in the lowest income quartile. The results do not provide support for a
uniformly extension of pension age for all.
PMID- 28515192
TI - Study protocol for a transversal study to develop a screening model for excessive
gambling behaviours on a representative sample of users of French authorised
gambling websites.
AB - INTRODUCTION: Since the legalisation of online gambling in France in 2010,
gambling operators must implement responsible gambling measures to prevent
excessive gambling practices. However, actually there is no screening procedure
for identifying problematic gamblers. Although several studies have already been
performed using several data sets from online gambling operators, the authors
deplored several methodological and clinical limits that prevent scientifically
validating the existence of problematic gambling behaviour. The aim of this study
is to develop a model for screening excessive gambling practices based on the
gambling behaviours observed on French gambling websites, coupled with a clinical
validation. METHODS AND ANALYSIS: The research is divided into three successive
stages. All analyses will be performed for each major type of authorised online
gambling in France. The first stage aims at defining a typology of users of
French authorised gambling websites based on their gambling behaviour. This
analysis will be based on data from the Authority for Regulating Online Gambling
(ARJEL) and the Francaise Des Jeux (FDJ). For the second stage aiming at
determining a score to predict whether a gambler is problematic or not, we will
cross answers from the Canadian Problem Gambling Index with real gambling data.
The objective of the third stage is to clinically validate the score previously
developed. Results from the screening model will be compared (using sensitivity,
specificity, area under the curve, and positive and negative predictive values)
with the diagnosis obtained with a telephone clinical interview, including
diagnostic criteria for gambling addiction. ETHICS AND DISSEMINATION: This study
was approved by the local Research Ethics Committee (GNEDS) on 25 March 2015.
Results will be presented in national and international conferences, submitted to
peer-reviewed journals and will be part of a PhD thesis. A final report with the
study results will be presented to the ARJEL, especially the final screening
model. TRIAL REGISTRATION NUMBER: NCT02415296.
PMID- 28515190
TI - Interaction of ACE genotype and salt intake on hypertension among Chinese
Kazakhs: results from a population-based cross-sectional study.
AB - OBJECTIVES: To explore the effect of interaction between ACE genotype and salt
intake on hypertension among Chinese Kazakhs, and to compare applications of
interactions between logistic model and generalised partially linear tree-based
regression (GPLTR) model. DESIGN: Population-based cross-sectional study.
SETTING: Hong Dun, North Xinjiang, China. PARTICIPANTS: Non-consanguineous
Chinese Kazakh participants (n=916, 342 men and 574 women) aged >=30 years. MAIN
OUTCOME MEASURES: Association between ACE genotype and hypertension, association
between salt intake and hypertension, and interaction of ACE genotype and salt
intake on hypertension in two models. RESULTS: Associations between salt intake
and hypertension were different in ACE genotype of II and ID+DD. Under the
logistic models, main and interaction effects were not observed for men, but
effects were present in opposite directions for women (main effect of ACE:
OR=0.20, p=0.003; interaction effect: OR=1.07, p=0.027). Under the GPLTR model,
Bayesian information criterion trees included both salt intake and ACE genotype
as split variables. Individuals with a salt intake >=19.5 g/day and ID+DD
genotypes had a 3.99-fold (p=0.004) higher risk of hypertension compared with the
II genotype for men, whereas salt intake <20.1 g/day and ID+DD genotypes had an
OR=0.55 (p=0.014) compared with the II genotype for women. CONCLUSIONS: An
interaction of ACE genotype and salt intake on hypertension was observed among
Chinese Kazakhs but in different ways according to sex. The GPLTR model appears
to be more suitable for an exploration of interactions in complex diseases.
PMID- 28515193
TI - Cost-effectiveness of telehealthcare to patients with chronic obstructive
pulmonary disease: results from the Danish 'TeleCare North' cluster-randomised
trial.
AB - OBJECTIVES: To investigate the cost-effectiveness of a telehealthcare solution in
addition to usual care compared with usual care. DESIGN: A 12-month cost-utility
analysis conducted alongside a cluster-randomised trial. SETTING: Community-based
setting in the geographical area of North Denmark Region in Denmark.
PARTICIPANTS: 26 municipality districts define randomisation clusters with 13
districts in each arm. 1225 patients with chronic obstructive pulmonary disease
were enrolled, of which 578 patients were randomised to telehealthcare and 647 to
usual care. INTERVENTIONS: In addition to usual care, patients in the
intervention group received a set of telehealthcare equipment and were monitored
by a municipality-based healthcare team. Patients in the control group received
usual care. MAIN OUTCOME MEASURE: Incremental costs per quality-adjusted life
years gained from baseline up to 12 months follow-up. RESULTS: From a healthcare
and social sector perspective, the adjusted mean difference in total costs
between telehealthcare and usual care was ?728 (95% CI -754 to 2211) and the
adjusted mean difference in quality-adjusted life-years gained was 0.0132 (95% CI
-0.0083 to 0.0346). The incremental cost-effectiveness ratio was ?55 327 per
quality-adjusted life-year gained. Decision-makers should be willing to pay more
than ?55 000 to achieve a probability of cost-effectiveness >50%. This conclusion
is robust to changes in the definition of hospital contacts and reduced
intervention costs. Only in the most optimistic scenario combining the effects of
all sensitivity analyses, does the incremental cost-effectiveness ratio fall
below the UK thresholds values (?21 068 per quality-adjusted life-year).
CONCLUSIONS: Telehealthcare is unlikely to be a cost-effective addition to usual
care, if it is offered to all patients with chronic obstructive pulmonary disease
and if the willingness-to-pay threshold values from the National Institute for
Health and Care Excellence are applied. TRIAL REGISTRATION: Clinicaltrials.gov,
NCT01984840, 14 November 2013.
PMID- 28515194
TI - Do patients and health care providers have discordant preferences about which
aspects of treatments matter most? Evidence from a systematic review of discrete
choice experiments.
AB - OBJECTIVES: To review studies eliciting patient and healthcare provider
preferences for healthcare interventions using discrete choice experiments (DCEs)
to (1) review the methodology to evaluate similarities, differences, rigour of
designs and whether comparisons are made at the aggregate level or account for
individual heterogeneity; and (2) quantify the extent to which they demonstrate
concordance of patient and healthcare provider preferences. METHODS: A systematic
review searching Medline, EMBASE, Econlit, PsycINFO and Web of Science for DCEs
using patient and healthcare providers. INCLUSION CRITERIA: peer-reviewed;
complete empiric text in English from 1995 to 31July 2015; discussing a
healthcare-related topic; DCE methodology; comparing patients and healthcare
providers. DESIGN: Systematic review. RESULTS: We identified 38 papers exploring
16 interventions in 26 diseases/indications. Methods to analyse results,
determine concordance between patient and physician values, and explore
heterogeneity varied considerably between studies. The majority of studies we
reviewed found more evidence of mixed concordance and discordance (n=28) or
discordance of patient and healthcare provider preferences (n=12) than of
concordant preferences (n=4). A synthesis of concordance suggested that
healthcare providers rank structure and outcome attributes more highly than
patients, while patients rank process attributes more highly than healthcare
providers. CONCLUSIONS: Discordant patient and healthcare provider preferences
for different attributes of healthcare interventions are common. Concordance
varies according to whether attributes are processes, structures or outcomes, and
therefore determining preference concordance should consider all aspects jointly
and not a binary outcome. DCE studies provide excellent opportunities to assess
value concordance between patients and providers, but assessment of concordance
was limited by a lack of consistency in the approaches used and consideration of
heterogeneity of preferences. Future DCEs assessing concordance should fully
report the framing of the questions and investigate the heterogeneity of
preferences within groups and how these compare.
PMID- 28515197
TI - Models for estimating and projecting global, regional and national prevalence and
disease burden of asthma: protocol for a systematic review.
AB - INTRODUCTION: Models that have so far been used to estimate and project the
prevalence and disease burden of asthma are in most cases inadequately described
and irreproducible. We aim systematically to describe and critique the existing
models in relation to their strengths, limitations and reproducibility, and to
determine the appropriate models for estimating and projecting the prevalence and
disease burden of asthma. METHODS: We will search the following electronic
databases to identify relevant literature published from 1980 to 2017: Medline,
Embase, WHO Library and Information Services and Web of Science Core Collection.
We will identify additional studies by searching the reference list of all the
retrieved papers and contacting experts. We will include observational studies
that used models for estimating and/or projecting prevalence and disease burden
of asthma regarding human population of any age and sex. Two independent
reviewers will assess the studies for inclusion and extract data from included
papers. Data items will include authors' names, publication year, study aims,
data source and time period, study population, asthma outcomes, study
methodology, model type, model settings, study variables, methods of model
derivation, methods of parameter estimation and/or projection, model fit
information, key findings and identified research gaps. A detailed critical
narrative synthesis of the models will be undertaken in relation to their
strengths, limitations and reproducibility. A quality assessment checklist and
scoring framework will be used to determine the appropriate models for estimating
and projecting the prevalence anddiseaseburden of asthma. ETHICS AND
DISSEMINATION: We will not collect any primary data for this review, and hence
there is no need for formal National Health Services Research Ethics Committee
approval. We will present our findings at scientific conferences and publish the
findings in the peer-reviewed scientific journal.
PMID- 28515196
TI - Cost-effectiveness of therapist-guided internet-delivered cognitive behaviour
therapy for paediatric obsessive-compulsive disorder: results from a randomised
controlled trial.
AB - OBJECTIVES: To evaluate the cost-effectiveness of a therapist-guided internet
delivered cognitive behaviour therapy (ICBT) intervention for adolescents with
obsessive-compulsive disorder (OCD) compared with untreated patients on a
waitlist. DESIGN: Single-blinded randomised controlled trial. SETTING: A research
clinic within the regular child and adolescent mental health service in
Stockholm, Sweden. PARTICIPANTS: Sixty-seven adolescents (12-17 years) with a
Diagnostic and Statistical Manual of Mental Disorders Fifth Edition diagnosis of
OCD. INTERVENTIONS: Either a 12-week, therapist-guided ICBT intervention or a
wait list condition of equal duration. PRIMARY OUTCOME MEASURES: Cost data were
collected at baseline and after treatment, including healthcare use, supportive
resources, prescription drugs, prescription-free drugs, school absence and
productivity loss, as well as the cost of ICBT. Health outcomes were defined as
treatment responder rate and quality-adjusted life years gain. Bootstrapped mixed
model analyses were conducted comparing incremental costs and health outcomes
between the groups from the societal and healthcare perspectives. RESULTS:
Compared with waitlist control, ICBT generated substantial societal cost savings
averaging US$-144.98 (95% CI -159.79 to -130.16) per patient. The cost reductions
were mainly driven by reduced healthcare use in the ICBT group. From the societal
perspective, the probability of ICBT being cost saving compared with waitlist
control was approximately 60%. From the healthcare perspective, the cost per
additional responder to ICBT compared with waitlist control was approximately
US$78. CONCLUSIONS: The results suggest that therapist-guided ICBT is a cost
effective treatment and results in societal cost savings, compared with patients
who do not receive evidence-based treatment. Since, at present, most patients
with OCD do not have access to evidence-based treatments, the results have
important implications for the increasingly strained national and healthcare
budgets. Future studies should compare the cost-effectiveness of ICBT with
regular face-to-face CBT. TRIAL REGISTRATION NUMBER: NCT02191631.
PMID- 28515195
TI - Cohort profile: internal migration in sub-Saharan Africa-The Migration and Health
in Malawi (MHM) study.
AB - PURPOSE: The Migration and Health in Malawi (MHM) study focuses on a key
challenge in migration research: although it has long been established that
migration and health are closely linked, identifying the effect of migration on
various health outcomes is complicated by methodological challenges. The MHM
study uses a longitudinal panel premigration and postmigration study design (with
a non-migrant comparison group) to measure and/or control for important
characteristics that affect both migration and health outcomes. PARTICIPANTS:
Data are available for two waves. The MHM interviewed 398 of 715 migrants in 2007
(55.7%) and 722 of 1013 in 2013 (71.3%); as well as 604 of 751 (80.4%) for a non
migrant reference group in 2013. The total interviewed sample size for the MHM in
both waves is 1809. These data include extensive information on lifetime
migration, socioeconomic and demographic characteristics, sexual behaviours,
marriage, household/family structure, social networks and social capital,
HIV/AIDS biomarkers and other dimensions of health. FINDINGS TO DATE: Our result
for the relationship between migration and health differs by health measure and
analytic approach. Migrants in Malawi have a significantly higher HIV prevalence
than non-migrants, which is primarily due to the selection of HIV-positive
individuals into migration. We find evidence for health selection; physically
healthier men and women are more likely to move, partly because migration selects
younger individuals. However, we do not find differences in physical or mental
health between migrants and non-migrants after moving. FUTURE PLANS: We are
preparing a third round of data collection for these (and any new) migrants,
which will take place in 2018. This cohort will be used to examine the effect of
migration on various health measures and behaviours, including general mental and
physical health, smoking and alcohol use, access to and use of health services
and use of antiretroviral therapy.
PMID- 28515198
TI - Post-authorisation passive enhanced safety surveillance of seasonal influenza
vaccines: protocol of a pilot study in England.
AB - AIM: To pilot enhanced safety surveillance of seasonal influenza vaccine meeting
the European Medicines Agency (EMA) requirement to rapidly detect a significant
increase in the frequency or severity of adverse events of interest (AEIs), which
may indicate risk from the new season's vaccine. STUDY DESIGN: A prospective
passive enhanced safety surveillance combining data collection from adverse drug
reaction (ADR) cards with automated collection of pseudonymised routinely
collected electronic health record (EHR) data. This study builds on a feasibility
study carried out at the start of the 2015/2016 influenza season. We will report
influenza vaccine exposure and any AEIs reported via ADR card or recorded
directly into the EHR, from the commencement of influenza vaccination and ends as
specified by EMA (30 November 2016). SETTING: Ten volunteer English general
practices, primarily using the GSK influenza vaccines. They had selected this
vaccine in advance of the study. PARTICIPANTS: People who receive a seasonal
influenza vaccine, in each age group defined in EMA interim guidance: 6 months to
5 years, 6-12 years, 13-17 years, 18-65 years and >65 years. OUTCOME MEASURES:
The primary outcome measure is the rate of AEIs occurring within 7 days
postvaccination, using passive surveillance of general practitioner (GP) EHR
systems enhanced by a card-based ADR reporting system. Extracted data will be
presented overall by brand (Fluarix Tetra vs others), by age strata and risk
groups. The secondary outcome measure is the vaccine uptake among the subjects
registered in the enrolled general practices. ETHICS AND DISSEMINATION: Ethical
approval was granted by the Proportionate Review Sub-committee of the North East
Newcastle & North Tyneside 2 on 5 August 2016. The study received approval from
the Health Research Authority on 1 September 2016. We will produce an interim
analysis within 8 weeks, and an end-of-study report, which will be submitted to
peer-reviewed journals.
PMID- 28515199
TI - Are healthcare aides underused in long-term care? A cross-sectional study on
continuing care facilities in Canada.
AB - OBJECTIVES: Over the last 10 years, appropriate workforce utilisation has been an
important discussion among healthcare practitioners and policy-makers. The role
of healthcare aides (HCAs) has also expanded to improve their utilisation. This
evolving role of HCAs in Canada has prompted calls for standardised training,
education and scope of practice for HCAs. The purpose of this research was to
examine the differences in HCAs training and utilisation in continuing care
facilities. DESIGN: From June 2014 to July 2015, we conducted a mixed-method
study on HCA utilisation in continuing care. This paper presents findings
gathered solely from the prospective cross-sectional survey of continuing care
facilities (long-term care (LTC) and supportive living (SL)) on HCA utilisation.
SETTING AND PARTICIPANTS: We conducted this study in a Western Canadian province.
The managers of the continuing care facilities (SL and LTC) were eligible to
participate in the survey. PRIMARY OUTCOME MEASURES: The pattern of HCAs
involvement in medication assistance and other care activities in SL and LTC
facilities. RESULTS: We received 130 completed surveys (LTC=64 and SL=52). Our
findings showed that approximately 81% of HCAs were fully certified. We found
variations in how HCAs were used in SL and LTC facilities. Overall, HCAs in SL
were more likely to be involved in medication management such as assisting with
inhaled medication and oral medication delivery. A significantly larger
proportion of survey respondents from SL facilities reported that medication
assistance training was mandatory for their HCAs (86%) compared with the LTC
facilities (50%) (p value <0.01). CONCLUSION: The utilisation of HCAs varies
widely between SL and LTC facilities. HCAs in SL facilities may be considered
better used according to their required educational training and competencies.
Expanding the role of HCAs in LTC facilities may lead to a cost-effective and
more efficient utilisation of workforce in continuing care facilities.
PMID- 28515200
TI - Impact of expedited partner therapy (EPT) implementation on chlamydia incidence
in the USA.
AB - OBJECTIVES: The diagnosis and treatment of Chlamydia trachomatis infection is
important in preventing persistent or recurrent infection. Expedited partner
therapy (EPT) is the favoured and supported method for STI treatment of the
Centers for Disease Control and Prevention when the provider cannot be assured
that all recent sexual partner(s) will seek therapy. EPT is legally permissible
in 38 states and is endorsed by healthcare organisations to decrease the rates of
chlamydia and gonorrhoea infection. Our study investigated the impact of EPT
legal status (permissible, potentially allowable or prohibited) on C. trachomatis
infection rates for each state. METHODS: Our ecological study modelled the number
of reported chlamydia cases from 2000 to 2013 as a function of year, legal status
and the interaction between year and legality. We used a negative binomial
regression model that included state fixed effects (including the District of
Columbia) to account for both the repeated measures per state and state-specific
characteristics that could not be measured for inclusion in this study. The
lagged number of C. trachomatis cases was included as a covariate and each
state's total population for a given year was included in the model as an
exposure parameter. States were designated Y (EPT permissible), N (EPT
prohibited) and M (EPT potentially allowable), and the legal status of each state
could vary over time. RESULTS: Each legal category saw an increase in the
incidence rate of C. trachomatis infection, but on average, the incidence rate
for states with prohibitive EPT legislation grew significantly faster over time
compared with the rate for the states where EPT was permissible. The average
increase in predicted incidence rates per year for states with Y, N and M legal
status were 14.1 (95% CI (12.0 to 16.2)), 17.5 (95% CI (15.9 to 19.2)) and 16.8
(95% CI (15.0 to 18.6)) cases per 100 000 persons per year, respectively, when
controlling for state-specific effects. CONCLUSIONS: Our model suggests that a
lack of EPT legislation is associated with an increase in STI rates. States with
potentially allowable EPT legislation as of 2013 (n=8) should consider permitting
EPT as a component of a multipronged strategy for treatment of sexual partners to
prevent C. trachomatis infection.
PMID- 28515201
TI - Pre- versus post-mass extinction divergence of Mesozoic marine reptiles dictated
by time-scale dependence of evolutionary rates.
AB - The fossil record of a major clade often starts after a mass extinction even
though evolutionary rates, molecular or morphological, suggest its pre-extinction
emergence (e.g. squamates, placentals and teleosts). The discrepancy is larger
for older clades, and the presence of a time-scale-dependent methodological bias
has been suggested, yet it has been difficult to avoid the bias using Bayesian
phylogenetic methods. This paradox raises the question of whether ecological
vacancies, such as those after mass extinctions, prompt the radiations. We
addressed this problem by using a unique temporal characteristic of the
morphological data and a high-resolution stratigraphic record, for the oldest
clade of Mesozoic marine reptiles, Ichthyosauromorpha. The evolutionary rate was
fastest during the first few million years of ichthyosauromorph evolution and
became progressively slower over time, eventually becoming six times slower.
Using the later slower rates, estimates of divergence time become excessively
older. The fast, initial rate suggests the emergence of ichthyosauromorphs after
the end-Permian mass extinction, matching an independent result from high
resolution stratigraphic confidence intervals. These reptiles probably invaded
the sea as a new ecosystem was formed after the end-Permian mass extinction. Lack
of information on early evolution biased Bayesian clock rates.
PMID- 28515202
TI - Does coevolution with a shared parasite drive hosts to partition their defences
among species?
AB - When mimicry imposes costs on models, selection may drive the model's phenotype
to evolve away from its mimic. For example, brood parasitism often drives hosts
to diversify in egg appearance among females within a species, making mimetic
parasitic eggs easier to detect. However, when a single parasite species exploits
multiple host species, parasitism could also drive host egg evolution away from
other co-occurring hosts, to escape susceptibility to their respective mimics.
This hypothesis predicts that sympatric hosts of the same parasite should
partition egg phenotypic space (defined by egg colour, luminance and pattern)
among species to avoid one another. We show that eggs of warbler species
parasitized by the cuckoo finch Anomalospiza imberbis in Zambia partition
phenotypic space much more distinctly than do eggs of sympatric but unparasitized
warblers. Correspondingly, cuckoo finch host-races better match their own
specialist host than other local host species. In the weaver family, parasitized
by the diederik cuckoo Chrysococcyx caprius, by contrast, parasitized species
were more closely related and overlapped extensively in phenotypic space;
correspondingly, cuckoos did not match their own host better than others. These
results suggest that coevolutionary arms races between hosts and parasites may be
shaped by the wider community context in which they unfold.
PMID- 28515203
TI - Wild birds respond to flockmate loss by increasing their social network
associations to others.
AB - Understanding the consequences of losing individuals from wild populations is a
current and pressing issue, yet how such loss influences the social behaviour of
the remaining animals is largely unexplored. Through combining the automated
tracking of winter flocks of over 500 wild great tits (Parus major) with removal
experiments, we assessed how individuals' social network positions responded to
the loss of their social associates. We found that the extent of flockmate loss
that individuals experienced correlated positively with subsequent increases in
the number of their social associations, the average strength of their bonds and
their overall connectedness within the social network (defined as summed edge
weights). Increased social connectivity was not driven by general disturbance or
changes in foraging behaviour, but by modifications to fine-scale social network
connections in response to losing their associates. Therefore, the reduction in
social connectedness expected by individual loss may be mitigated by increases in
social associations between remaining individuals. Given that these findings
demonstrate rapid adjustment of social network associations in response to the
loss of previous social ties, future research should examine the generality of
the compensatory adjustment of social relations in ways that maintain the
structure of social organization.
PMID- 28515204
TI - A genetic legacy of introgression confounds phylogeny and biogeography in oaks.
AB - Oaks (Quercus L.) have long been suspected to hybridize in nature, and widespread
genetic exchange between morphologically defined species is well documented in
two- to six-species systems, but the phylogenetic consequences of hybridization
in oaks have never been demonstrated in a phylogenetically diverse sample. Here,
we present phylogenomic analyses of a ca 30 Myr clade that strongly support
morphologically defined species and the resolution of novel clades of white oaks;
however, historical hybridization across clade boundaries is detectable and,
undiagnosed, would obscure the imprint of biogeographic history in the phylogeny.
Phylogenetic estimation from restriction-site-associated DNA sequencing data for
156 individuals representing 81 species supports two successive intercontinental
disjunctions of white oaks: an early vicariance between the Eurasian and American
white oaks, and a second, independent radiation represented by two relictual
species. A suite of subsampled and partitioned analyses, however, supports a more
recent divergence of the Eurasian white oaks from within the American white oaks
and suggests that historic introgression between the Eurasian white oaks and a
now-relictual lineage biases concatenated phylogenetic estimates. We demonstrate
how divergence and reticulation both influence our understanding of the timing
and nature of diversification and global colonization in these ecologically and
economically important taxa.
PMID- 28515205
TI - Family network size and survival across the lifespan of female macaques.
AB - Two decades of research suggest social relationships have a common evolutionary
basis in humans and other gregarious mammals. Critical to the support of this
idea is growing evidence that mortality is influenced by social integration, but
when these effects emerge and how long they last is mostly unknown. Here, we
report in adult female macaques that the impact of number of close adult female
relatives, a proxy for social integration, on survival is not experienced
uniformly across the life course; prime-aged females with a greater number of
relatives had better survival outcomes compared with prime-aged females with
fewer relatives, whereas no such effect was found in older females. Group size
and dominance rank did not influence this result. Older females were less
frequent targets of aggression, suggesting enhanced experience navigating the
social landscape may obviate the need for social relationships in old age. Only
one study of humans has found age-based dependency in the association between
social integration and survival. Using the largest dataset for any non-human
animal to date, our study extends support for the idea that sociality promotes
survival and suggests strategies employed across the life course change along
with experience of the social world.
PMID- 28515206
TI - Widespread ecomorphological convergence in multiple fish families spanning the
marine-freshwater interface.
AB - The theoretical definition and quantification of convergence is an increasingly
topical focus in evolutionary research, with particular growing interest on study
scales spanning deep phylogenetic divergences and broad geographical areas. While
much progress has recently been made in understanding the role of convergence in
driving terrestrial (e.g. anole lizards) and aquatic (e.g. cichlids) radiations,
little is known about its macroevolutionary effects across environmental
gradients. This study uses a suite of recently developed comparative approaches
integrating diverse aspects of morphology, dietary data, habitat affiliation and
phylogeny to assess convergence across several well-known tropical-temperate fish
families in the percomorph suborder Terapontoidei, a clade with considerable
phenotypic and ecological diversity radiating in both marine and freshwater
environments. We demonstrate significant widespread convergence across many
lineages occupying equivalent trophic niches, particularly feeding habits such as
herbivory and biting of attached prey off hard substrates. These include several
examples of convergent morphotypes evolving independently in marine and
freshwater clades, separated by deep evolutionary divergences (tens of millions
of years). The Terapontoidei present a new example of the macroevolutionary
dynamics of morphological and ecological coevolution in relation to habitat and
trophic preferences, at a greater phylogenetic and habitat scale than most well
studied adaptive radiations.
PMID- 28515208
TI - Glucocorticoid-responsive lymphocytic parathyroiditis and hypocalciuric
hypercalcemia due to autoantibodies against the calcium-sensing receptor: a case
report and literature review.
AB - OBJECTIVE: Autoimmune lymphocytic parathyroiditis and acquired hypocalciuric
hypercalcemia associated with autoantibodies against the calcium-sensing receptor
(anti-CaSR) are rare and poorly understood conditions. Here, we describe a
patient with acquired parathyroid hormone (PTH)-dependent hypercalcemia with
associated hypocalciuria, found to have true lymphocytic parathyroiditis on
histopathology, and circulating anti-CaSR antibodies in serum. DESIGN AND
METHODS: A 64-year-old woman was referred to our clinic for persistent
hypercalcemia after a subtotal parathyroidectomy. She was normocalcemic until the
age of 63 years when she was diagnosed with primary hyperparathyroidism. She
underwent subtotal parathyroidectomy with appropriate intraoperative PTH decline.
Two weeks post-parathyroidectomy, she presented with persistent hypercalcemia and
hyperparathyroidism. Urine studies revealed an inappropriately low 24-h urine
calcium (Ca)/creatinine clearance ratio. Surgical pathology was consistent with
true lymphocytic parathyroiditis with lymphoid follicles. The presence of
circulating anti-CaSR antibodies was detected by immunoprecipitation of CaSR by
the patient's serum. After a 4-week course of prednisone, serum Ca and PTH
normalized, and her anti-CaSR titers declined. She remains normocalcemic 10
months after the discontinuation of glucocorticoid therapy. We present this
patient in the context of the relevant published literature on lymphocytic
parathyroiditis and acquired hypocalciuric hypercalcemia related to anti-CaSR
antibodies. CONCLUSIONS: Autoimmune lymphocytic parathyroiditis and acquired
hypocalciuric hypercalcemia associated with anti-CaSR antibodies is a very rare
yet important condition to be considered in a patient with acquired PTH-dependent
hypercalcemia with inappropriate hypocalciuria. Although subtotal
parathyroidectomy is unlikely to correct the hypercalcemia, this entity may
respond to a short course of prednisone therapy.
PMID- 28515207
TI - Early social learning triggers neurogenomic expression changes in a swordtail
fish.
AB - Mate choice can play a pivotal role in the nature and extent of reproductive
isolation between species. Mating preferences are often dependent on an
individual's social experience with adult phenotypes throughout development. We
show that olfactory preference in a swordtail fish (Xiphophorus malinche) is
affected by previous experience with adult olfactory signals. We compare
transcriptome-wide gene expression levels of pooled sensory and brain tissues
between three treatment groups that differ by social experience: females with no
adult exposure, females exposed to conspecifics and females exposed to
heterospecifics. We identify potential functionally relevant genes and biological
pathways differentially expressed not only between control and exposure groups,
but also between groups exposed to conspecifics and heterospecifics. Based on our
results, we speculate that vomeronasal receptor type 2 paralogs may detect
species-specific pheromone components and thus play an important role in
reproductive isolation between species.
PMID- 28515209
TI - For a healthier future: a virtuous cycle for reducing exposure to persistent
organic pollutants.
AB - In the modern society, people are exposed to various pollutants during their
lifetime. Worldwide, the status of children's health has changed in recent
decades. Some studies have attempted to identify the causes of these changes and
whether they relate to pollutant exposure; however, such attempts have faced
major challenges because human life is complex, involving many social and
environmental factors. Several long-term cohort studies are being conducted to
determine the relationship between diseases and social and environmental factors
in children. Even before we establish complete proof of adverse effects, we
should attempt to decrease risk to future generations by adopting precautionary
principles. Environmental exposure to persistent organic pollutants can be
reduced throughout the stages of life-the fetal period, newborn and infant
periods, childhood, adolescence and adulthood (preconception) by individuals as
well as by society as a whole. Through reducing environmental exposure to
pollutants, adverse health effects can also be reduced, which will contribute to
healthier future generations. Here, we suggest a virtuous cycle for improving the
health of future generations through reduced exposure to persistent pollutants.
PMID- 28515211
TI - Functional Equivalence of the SOX2 and SOX3 Transcription Factors in the
Developing Mouse Brain and Testes.
AB - Gene duplication provides spare genetic material that evolution can craft into
new functions. Sox2 and Sox3 are evolutionarily related genes with overlapping
and unique sites of expression during embryogenesis. It is currently unclear
whether SOX2 and SOX3 have identical or different functions. Here, we use
CRISPR/Cas9-assisted mutagenesis to perform a gene-swap, replacing the Sox3 ORF
with the Sox2 ORF to investigate their functional equivalence in the brain and
testes. We show that increased expression of SOX2 can functionally replace SOX3
in the development of the infundibular recess/ventral diencephalon, and largely
rescues pituitary gland defects that occur in Sox3 null mice. We also show that
ectopic expression of SOX2 in the testes functionally rescues the spermatogenic
defect of Sox3 null mice, and restores gene expression to near normal levels.
Together, these in vivo data provide strong evidence that SOX2 and SOX3 proteins
are functionally equivalent.
PMID- 28515210
TI - Impact of perceived control on all-cause and cardiovascular disease mortality in
three urban populations of Central and Eastern Europe: the HAPIEE study.
AB - BACKGROUND: Inverse associations between perceived control and cardiovascular
disease (CVD) have been reported in studies from Western Europe and the USA. To
assess this relationship across different populations, we investigated the
association between perceived control and all-cause and CVD mortality in three
population-based cohorts of Eastern European countries. METHODS: We analysed data
from a prospective cohort study in random population samples in Krakow (Poland),
Novosibirsk (Russia) and six Czech towns. Baseline survey included structured
questionnaire and objective examination in a clinic. Perceived control was
assessed using an 11-item scale developed by the MacArthur Foundation Programme
on Successful Midlife. Information on vital status was obtained from death
registers. Effect of perceived control on mortality was assessed using Cox
proportional hazards models. RESULTS: A total of 2377 deaths (1003 from CVD)
occurred among 27 249 participants over a median 7-year follow-up. In the Czech
and Polish cohorts, perceived control was inversely associated with mortality;
the adjusted HRs for the lowest versus highest control quintiles were 1.71 (1.34
to 2.19) in men and 1.63 (1.14 to 2.35) in women for all-cause mortality and 2.31
(1.48 to 3.59) and 5.50 (2.14 to 14.13) for CVD deaths. There was no association
between perceived control and mortality in Russia; the adjusted HRs for all-cause
mortality were 1.03 (0.79 to 1.34) in men and 1.29 (0.82 to 2.02) in women.
CONCLUSIONS: Low perceived control was associated with increased risk of all
cause and CVD mortality in Czech and Polish cohorts but not in Russia. It is
possible that this inconsistency may partly reflect a different sociocultural
understanding of the concept of control in Russia.
PMID- 28515212
TI - Regulation of WNT Signaling at the Neuromuscular Junction by the Immunoglobulin
Superfamily Protein RIG-3 in Caenorhabditis elegans.
AB - Perturbations in synaptic function could affect the normal behavior of an animal,
making it important to understand the regulatory mechanisms of synaptic
signaling. Previous work has shown that in Caenorhabditis elegans an
immunoglobulin superfamily protein, RIG-3, functions in presynaptic neurons to
maintain normal acetylcholine receptor levels at the neuromuscular junction
(NMJ). In this study, we elucidate the molecular and functional mechanism of RIG
3. We demonstrate by genetic and BiFC (Bi-molecular Fluorescence Complementation)
assays that presynaptic RIG-3 functions by directly interacting with the
immunoglobulin domain of the nonconventional Wnt receptor, ROR receptor tyrosine
kinase (RTK), CAM-1, which functions in postsynaptic body-wall muscles. This
interaction in turn inhibits Wnt/LIN-44 signaling through the ROR/CAM-1 receptor,
and allows for maintenance of normal acetylcholine receptor, AChR/ACR-16, levels
at the neuromuscular synapse. Further, this work reveals that RIG-3 and ROR/CAM-1
function through the beta-catenin/HMP-2 at the NMJ. Taken together, our results
demonstrate that RIG-3 functions as an inhibitory molecule of the Wnt/LIN-44
signaling pathway through the RTK, CAM-1.
PMID- 28515213
TI - Rapid Identification of Five Classes of Carbapenem Resistance Genes Directly from
Rectal Swabs by Use of the Xpert Carba-R Assay.
AB - Carbapenemase-producing organisms (CPO) have been identified by global health
leaders as an urgent threat. Detection of patients with gastrointestinal carriage
of CPO is necessary to interrupt their spread within health care facilities. In
this multisite study, we assessed the performance of the Xpert Carba-R test, a
rapid real-time quantitative PCR (qPCR) assay that detects five families of
carbapenemase genes (blaIMP, blaKPC, blaNDM, blaOXA-48, and blaVIM) directly from
rectal swab specimens. Using dual swabs, specimens from 755 patients were
collected and tested prospectively. An additional 432 contrived specimens were
prepared by seeding well-characterized carbapenem-susceptible and -nonsusceptible
strains into a rectal swab matrix and inoculating them onto swabs prior to
testing. Antimicrobial susceptibility testing, broth enriched culture, and DNA
sequencing were performed by a central laboratory blind to the Xpert Carba-R
results. The Xpert Carba-R assay demonstrated a positive percentage of agreement
(PPA) between 60 and 100% for four targets (blaKPC, blaNDM, blaVIM, and blaOXA
48) and a negative percentage of agreement (NPA) ranging between 98.9 and 99.9%
relative to the reference method (culture and sequencing of any carbapenem
nonsusceptible isolate). There were no prospective blaIMP-positive samples.
Contrived specimens demonstrated a PPA between 95 and 100% and an NPA of 100% for
all targets. Testing of rectal swabs directly using the Xpert Carba-R assay is
effective for rapid detection and identification of CPO from hospitalized
patients.
PMID- 28515214
TI - Assessment of a New Lower-Cost Real-Time PCR Assay for Detection of High-Risk
Human Papillomavirus: Useful for Cervical Screening in Limited-Resource Settings?
AB - Inexpensive and easy-to-perform human papillomavirus (HPV) tests are needed for
primary cervical cancer screening in lower-resource regions. In a convenience
sample of 516 residual exfoliative cervical specimens from the Kaiser Permanente
Northern California and U.S. National Cancer Institute Persistence and
Progression Study, we assessed the agreement and clinical performance of a
simple, inexpensive real-time PCR assay for the detection of 13 carcinogenic HPV
types (the H13 assay; Hybribio, Hong Kong) that is marketed in limited-resource
settings compared to previous testing by the Hybrid Capture 2 assay (HC2; Qiagen,
Germantown, MD) and the Onclarity assay (BD Diagnostics, Sparks, MD). The test
set was chosen to include many HPV-positive specimens. The reference standard was
a combination of HC2 and Onclarity results for HPV detection and histologic
diagnosis of controls (less than cervical intraepithelial neoplasia grade 2
[=4 positive nodes and
should be strongly considered for 1 to 3 positive lymph nodes and select patients
with node-negative disease deemed at high risk for recurrence.
PMID- 28515244
TI - What, When, and How of Biomarker Testing in Non-Small Cell Lung Cancer.
AB - Biomarker testing is recommended for all patients diagnosed with non-small cell
lung cancer. At a minimum, testing should include the mutations/fusions EGFR,
ALK, ROS1, and the protein programmed death ligand-1 (PD-L1), because FDA
approved therapies are available for these alterations. Other actionable
molecular findings include RET rearrangements, BRAFV600E mutations, and MET exon
14 alterations. If adequate testing was not performed at treatment initiation,
molecular testing should be performed before administration of subsequent lines
of therapy. In patients with EGFR-mutant lung cancer, when resistance develops,
physicians should seek to identify the T790M mutation using plasma and tissue
assays, because osimertinib therapy is available for this mutation.
PMID- 28515245
TI - Biomarker-Based Treatment Selection in Non-Small Cell Lung Cancer.
AB - Patients with non-small cell lung cancer must be tested for biomarkers.
Currently, treatments directed against EGFR, ALK, and ROS1 mutations are standard
of care. A number of emerging new targets and treatments are on the horizon.
PMID- 28515246
TI - Immunotherapies for Lung Cancer.
AB - In 2017, immunotherapy is the standard of care for patients with non-small cell
lung cancer (NSCLC) either in the first or second line depending on programmed
death ligand-1 (PD-L1) and mutation status. For first-line therapy, pembrolizumab
is currently the standard of care for patients whose tumors express PD-L1 >50%.
All patients with NSCLC should undergo PD-L1 testing before initiating treatment
on pembrolizumab. For patients not eligible in the first line, immunotherapy is
the standard of care for most in the second line. Nivolumab and atezolizumab are
approved in all patients as second-line therapies after platinum-based doublet
failure regardless PD-L1 expression level, although pembrolizumab is approved as
second-line therapy for those whose tumors express PD-L1 >1%.
PMID- 28515247
TI - Keynote Address: When Breath Becomes Air-As Physician Becomes Patient.
AB - As part of the NCCN 22nd Annual Conference: Improving the Quality, Effectiveness,
and Efficiency of Cancer Care, Lucy Kalanithi, MD, wife of now-deceased best
selling author Paul Kalanithi (When Breath Becomes Air), and Heather Wakelee, MD,
Paul's oncologist, discussed-for the first time together in a public forum-Paul's
experience of going from a neurosurgery resident to a patient with cancer with a
terminal diagnosis. Robert Carlson, MD, moderated the discussion.
PMID- 28515248
TI - Systemic Management of Colorectal Cancer.
AB - Advances have been made in the systemic treatment of colorectal cancer, with
approximately 12 chemotherapy or biologic agents approved for use as a single
agent or in a combination. However, numerous gaps in our understanding of the
disease remain, such as the lack of benefit with biologics in the adjuvant
setting, the absence of biomarkers for most systemic therapies, and the reason
why left-sided and right-sided tumors behave differently. At the 22nd NCCN Annual
Conference, Dr. Wells A. Messersmith presented several impactful updates to the
2017 NCCN Clinical Practice Guidelines in Oncology for Colon Cancer and reviewed
the outcomes with a host of therapies used for both early-stage and metastatic
disease.
PMID- 28515249
TI - Incorporating New Systemic Therapies in Kidney Cancer Treatment.
AB - In 2017, pazopanib and sunitinib remain the mainstays of frontline therapy for
advanced renal cell carcinoma. Independent review of frontline cabozantinib
therapy may alter standard of care for patients at intermediate and poor risk.
Multiple agents show a survival advantage in the second-line setting, including
nivolumab, cabozantinib, and combination lenvatinib and everolimus. Selection of
subsequent therapy will depend on patient disease status, comorbidities, and
resource availability.
PMID- 28515250
TI - Challenges of Toxicity Management in Immuno-Oncology.
AB - Immunotherapies are conveying unprecedented efficacy in some tumor types, but
with this success comes challenges in managing toxicities that are distinct from
those of cytotoxic agents. Although most immune-related adverse events can be
ameliorated by temporarily withholding the drug and administering steroids, grade
3 to 4 toxicities can be challenging and some adverse effects can be long
lasting. NCCN has developed an immunotherapy teaching and monitoring tool that
can help in evaluating and managing these autoimmune-mediated inflammatory
conditions, which can affect virtually all organ systems.
PMID- 28515251
TI - New Treatment Options for the Management of Multiple Myeloma.
AB - Multiple myeloma (MM) is a complex disease characterized by considerable genetic
heterogeneity. The updated NCCN Guidelines for MM have added new "preferred"
regimens for transplant and nontransplant candidates, and have moved some
formerly "preferred" regimens to the "other" category. Supportive care has
improved outcomes for patients, and new treatments in combination have extended
survival for patients with MM. Novel agents on the horizon are poised to raise
the bar even further.
PMID- 28515252
TI - Chronic Lymphocytic Leukemia: Individualizing Treatment Approach.
AB - A host of new therapies are now available for treating patients with chronic
lymphocytic leukemia (CLL) in both the upfront and relapsed or refractory
settings. Although the optimal use of these agents is still being defined,
established and emerging prognostic markers aid in the selection of appropriate
treatment with the best chance of success. At the NCCN 22nd Annual Conference,
Dr. Andrew Zelenetz discussed the role of the CLL-International Prognostic Index
for risk stratification, reviewed optimal first-line therapy options, and then
presented updated clinical trial data on the novel agents being used in the
relapsed or refractory setting. The hope is that chronic therapy will be replaced
by combinations that provide high rates of minimal residual disease negativity
with durable remissions.
PMID- 28515253
TI - Strategies for Management of Relapsed or Refractory Hodgkin Lymphoma.
AB - The advent of effective therapies has improved outcomes for those with newly
diagnosed Hodgkin lymphoma (HL), with a resulting cure rate of at least 80%.
However, with limited data on therapeutic options in the setting of advanced
disease, individualized treatment is recommended, and potential long-term effects
of therapy remain a key consideration. At the NCCN 22nd Annual Conference, Dr.
Leo I. Gordon explored strategies for systemic therapy in the relapsed or
refractory setting, focusing primarily on the standard of high-dose
therapy/autologous stem cell rescue, the CD30-targeted antibody drug conjugate
brentuximab vedotin, and checkpoint inhibition.
PMID- 28515254
TI - NCCN Debuts New Guidelines for Myeloproliferative Neoplasms.
AB - For the first time, NCCN has published guidelines specifically geared toward
treating myeloproliferative neoplasms (MPNs). The first set of guidelines was
developed for myelofibrosis (MF), and was presented at the NCCN 22nd Annual
Conference. Future guidelines will be issued for polycythemia vera, essential
thrombocytopenia, and atypical MPNs. Patients with MF can have an unpredictable
course, one that is largely dependent on the presence of certain molecular
alterations. Models are currently emerging that take into account molecular
factors. Only one drug is currently approved for MF, the oral JAK1/2 inhibitor
ruxolitinib, which has been shown to significantly reduce splenomegaly and
improve symptoms.
PMID- 28515255
TI - Active Systemic Treatment of Pancreatic Cancer.
AB - By 2020, pancreatic cancer is expected to be the second most common cause of
cancer-related death, exceeded only by lung cancer. During her presentation at
the NCCN 22nd Annual Conference, Dr. Margaret Tempero offered an update on the
current state of systemic treatment of pancreatic cancer, focusing on
resectable/borderline resectable, locally advanced, and metastatic disease.
PMID- 28515256
TI - Opportunities and Challenges: Human Papillomavirus and Cancer.
AB - Mucosal exposure to human papillomavirus (HPV) can lead to anogenital and head
and neck (H&N) cancer. Vaccination at a young age can be almost 100% effective in
preventing HPV infection with the viral subtypes in both men and women, at least
for disease in the anogenital tract. Therapeutic strategies targeting HPV in
cervical dysplasia and cancer are showing promise as well in regressing dysplasia
and controlling disease. That HPV-positive H&N cancer is a different disease from
HPV-negative disease, with different molecular and clinical features and
prognosis, is becoming better appreciated. At this time, however, the NCCN
Guidelines for H&N Cancers do not distinguish between the types. This is expected
to change.
PMID- 28515257
TI - Minimally Invasive Techniques for Treating Gynecologic Malignancies.
AB - For many women with endometrial and cervical cancers, minimally invasive surgery
represents an alternative standard of care to open abdominal procedures, with
fewer complications, better postoperative quality of life, and overall lower
cost. At the NCCN 22nd Annual Conference, Amanda N. Fader, MD, reviewed several
minimally invasive strategies for treating gynecologic cancers, including
conventional laparoscopy, robotic-assisted laparoscopy, sentinel lymph node
technology, and single-port surgery; highlighted some of the contemporary
literature on the role of these procedures; and explored some of the challenges
and barriers to their successful performance.
PMID- 28515258
TI - Evolving Treatment of Soft Tissue Sarcoma.
AB - Soft tissue sarcomas comprise multiple histologic subtypes, occur at a number of
anatomic sites, and require individualized treatment. Over the past 5 years, 4
new drugs were approved for sarcoma, most of which are driven by histology or the
anticipated response to treatment. Surgical resection remains the primary
treatment for resectable tumors. For unresectable or metastatic disease,
doxorubicin remains the backbone of chemotherapy, but other agents have improved
on its single-agent efficacy. Chief among them is olaratumab, which, in
combination with doxorubicin, is preferred over doxorubicin alone in the updated
NCCN Clinical Practice Guidelines in Oncology for Soft Tissue Sarcoma.
PMID- 28515259
TI - Novel Treatment Options for Neuroendocrine Tumors.
AB - Neuroendocrine tumors (NETs) are not as rare as once thought, with a current
prevalence that is estimated to be higher than that of many other
gastrointestinal tumors. Multiple treatment options are available for these
tumors, which are categorized according to their histology and site of origin.
For patients with metastatic disease, somatostatin analogues are often the
initial treatment, with other options considered when these drugs fail.
PMID- 28515260
TI - Multigene Testing for Hereditary Cancer: When, Why, and How.
AB - Multigene testing is a complicated area, with advantages and disadvantages of
testing for hereditary cancer syndromes. Currently, NCCN does not endorse routing
multiplex testing outside of a research setting, and/or intensive genetic
counseling regarding risks and benefits. The 2017 NCCN Clinical Practice
Guidelines in Oncology for Genetic/Familial High-Risk Assessment: Breast and
Ovarian and Colorectal provide suggestions for mutation carriers identified by
panel tests.
PMID- 28515261
TI - Life After Treatment: Quality-of-Life Concerns in Patients Treated for Cancer.
AB - Traditionally, the physical, psychological, and psychosocial long-term needs of
cancer survivors have received little attention compared with screening for
cancer recurrence and secondary cancers. The NCCN Clinical Practice Guidelines in
Oncology (NCCN Guidelines) for Survivorship offer recommendations for various
survivorship concerns, and those for improving menopausal symptoms were presented
at the NCCN 22nd Annual Conference. Key considerations in managing menopausal
symptoms in cancer survivors were reviewed, with chemotherapy-induced amenorrhea,
fertility concerns, and both hormonal and nonhormonal therapeutic options
featured.
PMID- 28515262
TI - Smoking Cessation in Patients With Cancer: Treatment Advances and the
Oncologist's Role.
AB - The harms of smoking cigarettes are well-known, and the benefits of smoking
cessation are well-established. Smoking cessation is especially important for
patients with cancer, because smoking compromises the effects of cancer treatment
and shortens survival. Interventions to achieve tobacco abstinence include
pharmacotherapy and counseling, and these often must be repeated. Patients should
be encouraged at every juncture to continue attempts to stop smoking.
PMID- 28515263
TI - Ligand-induced activation of human TRPM2 requires the terminal ribose of ADPR and
involves Arg1433 and Tyr1349.
AB - TRPM2 (transient receptor potential channel, subfamily melastatin, member 2) is a
Ca2+-permeable non-selective cation channel activated by the binding of adenosine
5'-diphosphoribose (ADPR) to its cytoplasmic NUDT9H domain (NUDT9 homology
domain). Activation of TRPM2 by ADPR downstream of oxidative stress has been
implicated in the pathogenesis of many human diseases, rendering TRPM2 an
attractive novel target for pharmacological intervention. However, the structural
basis underlying this activation is largely unknown. Since ADP (adenosine 5'
diphosphate) alone did not activate or antagonize the channel, we used a chemical
biology approach employing synthetic analogues to focus on the role of the ADPR
terminal ribose. All novel ADPR derivatives modified in the terminal ribose,
including that with the seemingly minor change of methylating the anomeric-OH,
abolished agonist activity at TRPM2. Antagonist activity improved as the terminal
substituent increasingly resembled the natural ribose, indicating that gating by
ADPR might require specific interactions between hydroxyl groups of the terminal
ribose and the NUDT9H domain. By mutating amino acid residues of the NUDT9H
domain, predicted by modelling and docking to interact with the terminal ribose,
we demonstrate that abrogating hydrogen bonding of the amino acids Arg1433 and
Tyr1349 interferes with activation of the channel by ADPR. Taken together, using
the complementary experimental approaches of chemical modification of the ligand
and site-directed mutagenesis of TRPM2, we demonstrate that channel activation
critically depends on hydrogen bonding of Arg1433 and Tyr1349 with the terminal
ribose. Our findings allow for a more rational design of novel TRPM2 antagonists
that may ultimately lead to compounds of therapeutic potential.
PMID- 28515264
TI - Functional characterization of the copper transcription factor AfMac1 from
Aspergillus fumigatus.
AB - Although copper functions as a cofactor in many physiological processes, copper
overload leads to harmful effects in living cells. Thus, copper homeostasis is
tightly regulated. However, detailed copper metabolic pathways have not yet been
identified in filamentous fungi. In this report, we investigated the copper
transcription factor AfMac1 ( Aspergillus fumigatusMac1 homolog) and identified
its regulatory mechanism in A. fumigatus AfMac1 has domains homologous to the DNA
binding and copper-binding domains of Mac1 from Saccharomyces cerevisiae, and
AfMac1 efficiently complemented Mac1 in S. cerevisiae Expression of Afmac1
resulted in CTR1 up-regulation, and mutation of the DNA-binding domain of Afmac1
failed to activate CTR1 expression in S. cerevisiae The Afmac1 deletion strain of
A. fumigatus failed to grow in copper-limited media, and its growth was restored
by introducing ctrC We found that AfMac1 specifically bound to the promoter
region of ctrC based on EMSA. The AfMac1-binding motif 5'-TGTGCTCA-3' was
identified from the promoter region of ctrC, and the addition of mutant ctrC
lacking the AfMac1-binding motif failed to up-regulate ctrC in A. fumigatus
Furthermore, deletion of Afmac1 significantly reduced strain virulence and
activated conidial killing activity by neutrophils and macrophages. Taken
together, these results suggest that AfMac1 is a copper transcription factor that
regulates cellular copper homeostasis in A. fumigatus.
PMID- 28515265
TI - Clinical marker for Alzheimer disease pathology in logopenic primary progressive
aphasia.
AB - OBJECTIVE: To determine whether logopenic features of phonologic loop dysfunction
reflect Alzheimer disease (AD) neuropathology in primary progressive aphasia
(PPA). METHODS: We performed a retrospective case-control study of 34 patients
with PPA with available autopsy tissue. We compared baseline and longitudinal
clinical features in patients with primary AD neuropathology to those with
primary non-AD pathologies. We analyzed regional neuroanatomic disease burden in
pathology-defined groups using postmortem neuropathologic data. RESULTS: A total
of 19/34 patients had primary AD pathology and 15/34 had non-AD pathology (13
frontotemporal lobar degeneration, 2 Lewy body disease). A total of 16/19 (84%)
patients with AD had a logopenic spectrum phenotype; 5 met published criteria for
the logopenic variant (lvPPA), 8 had additional grammatical or semantic deficits
(lvPPA+), and 3 had relatively preserved sentence repetition (lvPPA-). Sentence
repetition was impaired in 68% of patients with PPA with AD pathology; forward
digit span (DF) was impaired in 90%, substantially higher than in non-AD PPA
(33%, p < 0.01). Lexical retrieval difficulty was common in all patients with PPA
and did not discriminate between groups. Compared to non-AD, PPA with AD
pathology had elevated microscopic neurodegenerative pathology in the
superior/midtemporal gyrus, angular gyrus, and midfrontal cortex (p < 0.01). Low
DF scores correlated with high microscopic pathologic burden in
superior/midtemporal and angular gyri (p <= 0.03). CONCLUSIONS: Phonologic loop
dysfunction is a central feature of AD-associated PPA and specifically correlates
with temporoparietal neurodegeneration. Quantitative measures of phonologic loop
function, combined with modified clinical lvPPA criteria, may help discriminate
AD-associated PPA.
PMID- 28515267
TI - Presurgical thalamic "hubness" predicts surgical outcome in temporal lobe
epilepsy.
AB - OBJECTIVE: To characterize the presurgical brain functional architecture
presented in patients with temporal lobe epilepsy (TLE) using graph theoretical
measures of resting-state fMRI data and to test its association with surgical
outcome. METHODS: Fifty-six unilateral patients with TLE, who subsequently
underwent anterior temporal lobectomy and were classified as obtaining a seizure
free (Engel class I, n = 35) vs not seizure-free (Engel classes II-IV, n = 21)
outcome at 1 year after surgery, and 28 matched healthy controls were enrolled.
On the basis of their presurgical resting-state functional connectivity, network
properties, including nodal hubness (importance of a node to the network; degree,
betweenness, and eigenvector centralities) and integration (global efficiency),
were estimated and compared across our experimental groups. Cross-validations
with support vector machine (SVM) were used to examine whether selective nodal
hubness exceeded standard clinical characteristics in outcome prediction.
RESULTS: Compared to the seizure-free patients and healthy controls, the not
seizure-free patients displayed a specific increase in nodal hubness (degree and
eigenvector centralities) involving both the ipsilateral and contralateral
thalami, contributed by an increase in the number of connections to regions
distributed mostly in the contralateral hemisphere. Simulating removal of
thalamus reduced network integration more dramatically in not seizure-free
patients. Lastly, SVM models built on these thalamic hubness measures produced
76% prediction accuracy, while models built with standard clinical variables
yielded only 58% accuracy (both were cross-validated). CONCLUSIONS: A thalamic
network associated with seizure recurrence may already be established
presurgically. Thalamic hubness can serve as a potential biomarker of surgical
outcome, outperforming the clinical characteristics commonly used in epilepsy
surgery centers.
PMID- 28515266
TI - Total small vessel disease score and risk of recurrent stroke: Validation in 2
large cohorts.
AB - OBJECTIVE: In patients with TIA and ischemic stroke, we validated the total small
vessel disease (SVD) score by determining its prognostic value for recurrent
stroke. METHODS: Two independent prospective studies were conducted, one
comprising predominantly Caucasian patients with TIA/ischemic stroke (Oxford
Vascular Study [OXVASC]) and one predominantly Chinese patients with ischemic
stroke (University of Hong Kong [HKU]). Cerebral MRI was performed and assessed
for lacunes, microbleeds, white matter hyperintensities (WMH), and perivascular
spaces (PVS). Predictive value of total SVD score for risk of recurrent stroke
was determined and potential refinements considered. RESULTS: In 2,002 patients
with TIA/ischemic stroke (OXVASC n = 1,028, HKU n = 974, 6,924 patient-years
follow-up), a higher score was associated with an increased risk of recurrent
ischemic stroke (adjusted hazard ratio [HR] per unit increase: 1.32, 1.16-1.51, p
< 0.0001; c statistic 0.61, 0.56-0.65, p < 0.0001) and intracerebral hemorrhage
(ICH) (HR 1.54, 1.11-2.13, p = 0.009; c statistic 0.65, 0.54-0.76, p = 0.006). A
higher score predicted recurrent stroke in SVD and non-SVD TIA/ischemic stroke
subtypes (c statistic 0.67, 0.59-0.74, p < 0.0001 and 0.60, 0.55-0.65, p <
0.0001). Including burden of microbleeds and WMH and adjusting the cutoff of
basal ganglia PVS potentially improved predictive power for ICH (c statistic
0.71, 0.60-0.81, phet = 0.45), but not for recurrent ischemic stroke (c statistic
0.60, 0.56-0.65, phet = 0.76) on internal validation. CONCLUSIONS: The total SVD
score has predictive value for recurrent stroke after TIA/ischemic stroke.
Prediction of recurrence in patients with nonlacunar events highlights the
potential role of SVD in wider stroke etiology.
PMID- 28515268
TI - Benefits, pitfalls, and future design of population-based registers in
neurodegenerative disease.
AB - Population-based disease registers identify and characterize all cases of
disease, including those that might otherwise be neglected. Prospective
population-based registers in neurodegeneration are necessary to provide
comprehensive data on the whole phenotypic spectrum and can guide planning of
health services. With the exception of the rare disease amyotrophic lateral
sclerosis, few complete population-based registers exist for neurodegenerative
conditions. Incomplete ascertainment, limitations and uncertainty in diagnostic
categorization, and failure to recognize sources of bias reduce the accuracy and
usefulness of many registers. Common biases include population stratification,
the use of prevalent rather than incident cases in earlier years, changes in
disease understanding and diagnostic criteria, and changing demographics over
time. Future registers are at risk of funding shortfalls and changes to privacy
legislation. Notwithstanding, as heterogeneities of clinical phenotype and
disease pathogenesis are increasingly recognized in the neurodegenerations, well
designed longitudinal population-based disease registers will be an essential
requirement to complete clinical understanding of neurodegenerative diseases.
PMID- 28515269
TI - Effect of omega-3 supplementation on neuropathy in type 1 diabetes: A 12-month
pilot trial.
AB - OBJECTIVE: To test the hypothesis that 12 months of seal oil omega-3
polyunsaturated fatty acids (omega-3 PUFA) supplementation will stop the known
progression of diabetic sensorimotor polyneuropathy (DSP) in type 1 diabetes
mellitus (T1DM). METHODS: Individuals with T1DM and evidence of DSP as determined
by a Toronto Clinical Neuropathy Score >=1 were recruited to participate in a
single-arm, open-label trial of seal oil omega-3 PUFA supplementation (10 mL.d-1;
750 mg eicosapentaenoic acid, 560 mg docosapentaenoic acid, and 1,020 mg
docosahexaenoic acid) for 1 year. The primary outcome was the 1-year change in
corneal nerve fiber length (CNFL) measured by in vivo corneal confocal
microscopy, with sensory and nerve conduction measures as secondary outcomes.
RESULTS: Forty participants (53% female), aged 48 +/- 14 years, body mass index
28.1 +/- 5.8 with diabetes duration of 27 +/- 18 years, were enrolled. At
baseline, 23 participants had clinical DSP and 17 did not. Baseline CNFL was 8.3
+/- 2.9 mm/mm2 and increased 29% to 10.1 +/- 3.7 mm/mm2 (p = 0.002) after 12
months of supplementation. There was no change in nerve conduction or sensory
function. CONCLUSIONS: Twelve months of omega-3 supplementation was associated
with increase in CNFL in T1DM. CLINICALTRIALSGOVIDENTIFIER: NCT02034266.
CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for
patients with T1DM and evidence of DSP, 12 months of seal oil omega-3
supplementation increases CNFL.
PMID- 28515271
TI - Imaging-based selection of patients for acute stroke treatment: Is it ready for
prime time?
PMID- 28515270
TI - Evaluation of hyperacute infarct volume using ASPECTS and brain CT perfusion core
volume.
AB - OBJECTIVE: To compare the accuracy of Alberta Stroke Program Early Computed
Tomography Score (ASPECTS) and CT perfusion to detect established infarction in
acute anterior circulation stroke. METHODS: We performed an observational study
in 59 acute anterior circulation ischemic stroke patients who underwent brain
noncontrast CT, CT perfusion, and MRI within 100 minutes from CT imaging. ASPECTS
scores were calculated by 4 blinded vascular neurologists. The accuracy of
ASPECTS and CT perfusion core volume to detect an acute MRI diffusion lesion of
>=70 mL was evaluated using receiver operating characteristics analysis and
optimum cutoff values were calculated using Youden J. RESULTS: Median ASPECTS
score was 8 (interquartile range [IQR] 5-9). Median CT perfusion core volume was
22 mL (IQR 10.4-71.9). Median MRI diffusion lesion volume was 24.5 mL (IQR 10
63.9). No significant difference was found between the accuracy of CT perfusion
and ASPECTS (c statistic 0.95 vs 0.87, p value for difference = 0.17). The
optimum ASPECTS cutoff score to detect a diffusion-weighted imaging lesion >=70
mL was <7 (sensitivity 0.74, specificity 0.86, Youden J = 0.60) and the optimum
CT perfusion core volume cutoff was >=50 mL (sensitivity 0.86, specificity 0.97,
Youden J = 0.84). The CT perfusion core lesion covered a median of 100% (IQR 86%
100%) of the acute MRI lesion volume (Pearson R = 0.88; R2 = 0.77). CONCLUSIONS:
We found no significant difference between the accuracy of CT perfusion and
ASPECTS to predict hyperacute MRI lesion volume in ischemic stroke.
PMID- 28515273
TI - Thalamus as a "hub" to predict outcome after epilepsy surgery.
PMID- 28515272
TI - Racial disparities in neurologic health care access and utilization in the United
States.
AB - OBJECTIVE: To evaluate racial and ethnic differences in the utilization of
neurologic care across a wide range of neurologic conditions in the United
States. METHODS: We analyzed nationally representative data from the 2006-2013
Medical Expenditure Panel Survey (MEPS), including information on demographics,
patient-reported health conditions, neurology visit rates, and costs. Using
diagnostic codes, we identified persons with any self-identified neurologic
disorder except back pain, as well as 5 subgroups (Parkinson disease, multiple
sclerosis, headache, cerebrovascular disease, and epilepsy). To assess
disparities in neurologic care utilization, we performed logistic regression
analyses of outpatient department neurologic care visit rates and expenditures
for each racial ethnic group controlling for age, sex, health status,
socioeconomic characteristics, and geographic region of care. RESULTS: Of the
279,103 MEPS respondents, 16,936 (6%) self-reported a neurologic condition; 5,890
(2%) received a total of 13,685 outpatient neurology visits. Black participants
were nearly 30% less likely to see an outpatient neurologist (odds ratio [OR]
0.72, confidence interval [CI] 0.64-0.81) relative to their white counterparts,
even after adjustment for demographic, insurance, and health status differences.
Hispanic participants were 40% less likely to see an outpatient neurologist (OR
0.61, CI 0.54-0.69). Among participants with known neurologic conditions, blacks
were more likely to be cared for in the emergency department, to have more
hospital stays, and to have higher per capita inpatient expenditures than their
white counterparts. CONCLUSIONS: Our findings highlight racial and ethnic
inequalities in the utilization of neurologic care in the United States.
PMID- 28515274
TI - Beyond clinical syndromes in primary progressive aphasia: Seeking etiologic
diagnoses.
PMID- 28515275
TI - Autophagy in the presynaptic compartment in health and disease.
AB - Synapses are functionally distinct neuronal compartments that are critical for
brain function, with synaptic dysfunction being an early pathological feature in
aging and disease. Given the large number of proteins needed for synaptic
function, the proliferation of defective proteins and the subsequent loss of
protein homeostasis may be a leading cause of synaptic dysfunction. Autophagic
mechanisms are cellular digestion processes that recycle cellular components and
contribute to protein homeostasis. Autophagy is important within the nervous
system, but its function in specific compartments such as the synapse has been
unclear. Evidence from research on both autophagy and synaptic function suggests
that there are links between the two and that synaptic homeostasis during aging
requires autophagy to regulate protein homeostasis. Exciting new work on
autophagy-modulating proteins that are enriched at the synapse has begun to link
autophagy to synapses and synaptic dysfunction in disease. A better understanding
of these links will help us harness the potential therapeutic benefits of
autophagy in combating age-related disorders of the nervous system.
PMID- 28515276
TI - Assembly of the U5 snRNP component PRPF8 is controlled by the HSP90/R2TP
chaperones.
AB - Splicing is catalyzed by the spliceosome, a complex of five major small nuclear
ribonucleoprotein particles (snRNPs). The pre-mRNA splicing factor PRPF8 is a
crucial component of the U5 snRNP, and together with EFTUD2 and SNRNP200, it
forms a central module of the spliceosome. Using quantitative proteomics, we
identified assembly intermediates containing PRPF8, EFTUD2, and SNRNP200 in
association with the HSP90/R2TP complex, its ZNHIT2 cofactor, and additional
proteins. HSP90 and R2TP bind unassembled U5 proteins in the cytoplasm, stabilize
them, and promote the formation of the U5 snRNP. We further found that PRPF8
mutants causing Retinitis pigmentosa assemble less efficiently with the U5 snRNP
and bind more strongly to R2TP, with one mutant retained in the cytoplasm in an
R2TP-dependent manner. We propose that the HSP90/R2TP chaperone system promotes
the assembly of a key module of U5 snRNP while assuring the quality control of
PRPF8. The proteomics data further reveal new interactions between R2TP and the
tuberous sclerosis complex (TSC), pointing to a potential link between growth
signals and the assembly of key cellular machines.
PMID- 28515279
TI - Regulatory Eosinophils Suppress T Cells Partly through Galectin-10.
AB - Eosinophils have the capacity to regulate the function of T cell subsets. Our aim
was to test the hypothesis of the existence of a regulatory subset of
eosinophils. Human eosinophils were incubated with T cells that were stimulated
with allogeneic leukocytes or CD3/CD28 cross-linking. After 2 d of coculture, 11%
of the eosinophils gained CD16 expression. A CD16hi subset of eosinophils,
encompassing 1-5% of all eosinophils, was also identified in the blood of healthy
subjects. FACS sorting showed that these CD16hi eosinophils were significantly
stronger suppressors of T cell proliferation than were conventional CD16neg
eosinophils. Human eosinophils contain stores of the immunoregulatory protein
galectin-10. We found that Ab-mediated neutralization of galectin-10 partially
abrogated the suppressive function of the eosinophils. Moreover, recombinant
galectin-10 by itself was able to suppress T cell proliferation. Finally, we
detected galectin-10-containing immune synapses between eosinophils and
lymphocytes. To conclude, we describe a subset of suppressive eosinophils
expressing CD16 that may escape detection because CD16-based negative selection
is the standard procedure for the isolation of human eosinophils. Moreover, we
show that galectin-10 functions as a T cell-suppressive molecule in eosinophils.
PMID- 28515278
TI - Critical Role of P2Y12 Receptor in Regulation of Th17 Differentiation and
Experimental Autoimmune Encephalomyelitis Pathogenesis.
AB - Adenosine 5'-diphosphate is a key endogenous cell-signaling molecule that can
activate P2 purinergic receptor family members. ADP-P2Y signaling is reported to
be associated with inflammation, but its function in T cell differentiation and
autoimmune diseases pathogenesis is unclear. In this study, we found that the
P2Y12 receptor was upregulated in the peripheral immune tissues of experimental
autoimmune encephalomyelitis (EAE) mice. Deficiency of P2Y12 led to a reduced
peak severity and cumulative disease score in EAE mice, followed by a dramatic
reduction of leukocyte infiltration and less extensive demyelination. The
percentage of Th17, one of the main pathogenic T cells in EAE, was sharply
decreased in P2Y12 knockout mice, accompanied by decreased IL-17A production and
a low mRNA level of Th17-related genes. In vitro culture assay further verified
that P2Y12 directly regulated Th17 differentiation. More interestingly,
clopidogrel and ticagrelor, two P2Y12-specific antagonists, effectively
alleviated the disease severity of EAE and inhibited Th17 differentiation both in
vivo and in vitro. Further study demonstrated that blocking the P2Y12 receptor
also ameliorated the symptoms of 2,4,6-trinitrobenzenesulfonic acid-induced
colitis and multiple low-dose streptozocin-induced type 1 diabetes. Our findings
not only revealed the critical role of P2Y12 in Th17 differentiation and EAE
pathogenesis, but also suggested the promising potential of P2Y12 antagonists in
the treatment of autoimmune diseases.
PMID- 28515280
TI - Airway Epithelial Cells Are Crucial Targets of Glucocorticoids in a Mouse Model
of Allergic Asthma.
AB - Although glucocorticoids (GCs) are a mainstay in the clinical management of
asthma, the target cells that mediate their therapeutic effects are unknown.
Contrary to our expectation, we found that GC receptor (GR) expression in immune
cells was dispensable for successful therapy of allergic airway inflammation
(AAI) with dexamethasone. Instead, GC treatment was compromised in mice
expressing a defective GR in the nonhematopoietic compartment or selectively
lacking the GR in airway epithelial cells. Further, we found that an intact GR
dimerization interface was a prerequisite for the suppression of AAI and airway
hyperresponsiveness by GCs. Our observation that the ability of dexamethasone to
modulate gene expression in airway epithelial cells coincided with its potency to
resolve AAI supports a crucial role for transcriptional regulation by the GR in
this cell type. Taken together, we identified an unknown mode of GC action in the
treatment of allergic asthma that might help to develop more specific therapies
in the future.
PMID- 28515277
TI - Histone chaperone HIRA regulates neural progenitor cell proliferation and
neurogenesis via beta-catenin.
AB - Histone cell cycle regulator (HIRA) is a histone chaperone and has been
identified as an epigenetic regulator. Subsequent studies have provided evidence
that HIRA plays key roles in embryonic development, but its function during early
neurogenesis remains unknown. Here, we demonstrate that HIRA is enriched in
neural progenitor cells, and HIRA knockdown reduces neural progenitor cell
proliferation, increases terminal mitosis and cell cycle exit, and ultimately
results in premature neuronal differentiation. Additionally, we demonstrate that
HIRA enhances beta-catenin expression by recruiting H3K4 trimethyltransferase
Setd1A, which increases H3K4me3 levels and heightens the promoter activity of
beta-catenin. Significantly, overexpression of HIRA, HIRA N-terminal domain, or
beta-catenin can override neurogenesis abnormities caused by HIRA defects.
Collectively, these data implicate that HIRA, cooperating with Setd1A, modulates
beta-catenin expression and then regulates neurogenesis. This finding represents
a novel epigenetic mechanism underlying the histone code and has profound and
lasting implications for diseases and neurobiology.
PMID- 28515281
TI - CXCL4 Exposure Potentiates TLR-Driven Polarization of Human Monocyte-Derived
Dendritic Cells and Increases Stimulation of T Cells.
AB - Chemokines have been shown to play immune-modulatory functions unrelated to
steering cell migration. CXCL4 is a chemokine abundantly produced by activated
platelets and immune cells. Increased levels of circulating CXCL4 are associated
with immune-mediated conditions, including systemic sclerosis. Considering the
central role of dendritic cells (DCs) in immune activation, in this article we
addressed the effect of CXCL4 on the phenotype and function of monocyte-derived
DCs (moDCs). To this end, we compared innate and adaptive immune responses of
moDCs with those that were differentiated in the presence of CXCL4. Already prior
to TLR- or Ag-specific stimulation, CXCL4-moDCs displayed a more matured
phenotype. We found that CXCL4 exposure can sensitize moDCs for TLR-ligand
responsiveness, as illustrated by a dramatic upregulation of CD83, CD86, and MHC
class I in response to TLR3 and TLR7/8-agonists. Also, we observed a markedly
increased secretion of IL-12 and TNF-alpha by CXCL4-moDCs exclusively upon
stimulation with polyinosinic-polycytidylic acid, R848, and CL075 ligands. Next,
we analyzed the effect of CXCL4 in modulating DC-mediated T cell activation.
CXCL4-moDCs strongly potentiated proliferation of autologous CD4+ T cells and
CD8+ T cells and production of IFN-gamma and IL-4, in an Ag-independent manner.
Although the internalization of Ag was comparable to that of moDCs, Ag processing
by CXCL4-moDCs was impaired. Yet, these cells were more potent at stimulating Ag
specific CD8+ T cell responses. Together our data support that increased levels
of circulating CXCL4 may contribute to immune dysregulation through the
modulation of DC differentiation.
PMID- 28515283
TI - Anisomorphic cortical reorganization in asymmetric sensorineural hearing loss.
AB - Acoustic trauma or inner ear disease may predominantly injure one ear, causing
asymmetric sensorineural hearing loss (SNHL). While characteristic frequency (CF)
map plasticity of primary auditory cortex (AI) contralateral to the injured ear
has been detailed, there is no study that also evaluates ipsilateral AI to
compare cortical reorganization across both hemispheres. We assess whether the
normal isomorphic mirror-image relationship between the two hemispheres is
maintained or disrupted in mild-to-moderate asymmetric SNHL of adult squirrel
monkeys. At week 24 after induction of acoustic injury to the right ear,
functional organization of the two hemispheres differs in direction and magnitude
of interaural CF difference, percentage of recording sites with spectrally
nonoverlapping binaural activation, and the concurrence of peripheral and central
activation thresholds. The emergence of this anisomorphic cortical reorganization
of the two hemispheres is replicated by simulation based on spike timing
dependent plasticity, where 1) AI input from the contralateral ear is dominant,
2) reestablishment of relatively shorter contralateral ear input timing drives
reorganization, and 3) only AI contralateral to the injured ear undergoes major
realignment of interaural frequency maps that evolve over months. Asymmetric SNHL
disrupts isomorphic organization between the two hemispheres and results in
relative local hemispheric autonomy, potentially impairing performance of tasks
that require binaural input alignment or interhemispheric processing.NEW &
NOTEWORTHY Mild-to-moderate hearing loss in one ear and essentially normal
hearing in the other triggers cortical reorganization that is different in the
two hemispheres. Asymmetry of cochlea sensitivities does not simply propagate to
the two auditory cortices in mirror-image fashion. The resulting anisomorphic
cortical reorganization may be a neurophysiological basis of clinical deficits in
asymmetric hearing loss, such as difficulty with hearing in noise, impaired
spatial hearing, and accelerated decline of the poorer ear.
PMID- 28515284
TI - Long-lasting increase in axonal excitability after epidurally applied DC.
AB - Effects of direct current (DC) on nerve fibers have primarily been investigated
during or just after DC application. However, locally applied cathodal DC was
recently demonstrated to increase the excitability of intraspinal preterminal
axonal branches for >1 h. The aim of this study was therefore to investigate
whether DC evokes a similarly long-lasting increase in the excitability of
myelinated axons within the dorsal columns. The excitability of dorsal column
fibers stimulated epidurally was monitored by recording compound action
potentials in peripheral nerves in acute experiments in deeply anesthetized rats.
The results show that 1) cathodal polarization (0.8-1.0 uA) results in a
severalfold increase in the number of epidurally activated fibers and 2) the
increase in the excitability appears within seconds, 3) lasts for >1 h, and 4) is
activity independent, as it does not require fiber stimulation during the
polarization. These features demonstrate an unexplored form of plasticity of
myelinated fibers and indicate the conditions under which it develops. They also
suggest that therapeutic effects of epidural stimulation may be significantly
enhanced if it is combined with DC polarization. In particular, by using DC to
increase the number of fibers activated by low-intensity epidural stimuli, the
low clinical tolerance to higher stimulus intensities might be overcome. The
activity independence of long-lasting DC effects would also allow the use of only
brief periods of DC polarization preceding epidural stimulation to increase the
effect.NEW & NOTEWORTHY The study indicates a new form of plasticity of
myelinated fibers. The differences in time course of DC-evoked increases in the
excitability of myelinated nerve fibers in the dorsal columns and in preterminal
axonal branches suggest that distinct mechanisms are involved in them. The
results show that combining epidural stimulation and transspinal DC polarization
may dramatically improve their outcome and result in more effective pain control
and the return of impaired motor functions.
PMID- 28515282
TI - Talin Plays a Critical Role in the Maintenance of the Regulatory T Cell Pool.
AB - Talin, a cytoskeletal protein essential in mediating integrin activation, has
been previously shown to be involved in the regulation of T cell proliferation
and function. In this study, we describe a role for talin in maintaining the
homeostasis and survival of the regulatory T (Treg) cell pool. T cell-specific
deletion of talin in Tln1fl/flCd4Cre mice resulted in spontaneous lymphocyte
activation, primarily due to numerical and functional deficiencies of Treg cells
in the periphery. Peripheral talin-deficient Treg cells were unable to maintain
high expression of IL-2Ralpha, resulting in impaired IL-2 signaling and
ultimately leading to increased apoptosis through downregulation of prosurvival
proteins Bcl-2 and Mcl-1. The requirement for talin in maintaining high IL
2Ralpha expression by Treg cells was due, in part, to integrin LFA-1-mediated
interactions between Treg cells and dendritic cells. Collectively, our data
suggest a critical role for talin in Treg cell-mediated maintenance of immune
homeostasis.
PMID- 28515285
TI - Cortical amplification models of experience-dependent development of selective
columns and response sparsification.
AB - The development of direction-selective cortical columns requires visual
experience, but the neural circuits and plasticity mechanisms that are
responsible for this developmental transition are unknown. To gain insight into
the mechanisms that could underlie experience-dependent increases in selectivity,
we explored families of cortical amplifier models that enhance weakly biased
feedforward signals. Here we focused exclusively on possible contributions of
cortico-cortical connections and took feedforward input to be constant. We
modeled pairs of interconnected columns that received equal and oppositely biased
inputs. In a single-element model of cortical columns, we found two ways that
cortical columns could receive biased feedforward input and exhibit strong but
unselective responses to stimuli: 1) within-column recurrent excitatory
connections could be strong enough to amplify both strong and weak feedforward
input, or 2) columns that received differently biased inputs could have strong
excitatory cross-connections that destroy selectivity. A Hebbian plasticity rule
combined with simulated experience with stimuli weakened these strong cross
connections across cortical columns, allowing the individual columns to respond
selectively to their biased inputs. In a model that included both excitatory and
inhibitory neurons in each column, an additional means of obtaining selectivity
through the cortical circuit was uncovered: cross-column suppression of
inhibition-stabilized networks. When each column operated as an inhibition
stabilized network, cross-column excitation onto inhibitory neurons forced
competition between the columns but in a manner that did not involve strong null
direction inhibition, consistent with experimental measurements of direction
selectivity in visual cortex. Experimental predictions of these possible
contributions of cortical circuits are discussed.NEW & NOTEWORTHY Sensory
circuits are initially constructed via mechanisms that are independent of sensory
experience, but later refinement requires experience. We constructed models of
how circuits that receive biased feedforward inputs can be initially unselective
and then be modified by experience and plasticity so that the resulting circuit
exhibits increased selectivity. We propose that neighboring cortical columns may
initially exhibit coupling that is too strong for selectivity. Experience
dependent mechanisms decrease this coupling so individual columns can exhibit
selectivity.
PMID- 28515286
TI - Responses of Purkinje cells in the oculomotor vermis of monkeys during smooth
pursuit eye movements and saccades: comparison with floccular complex.
AB - We recorded the responses of Purkinje cells in the oculomotor vermis during
smooth pursuit and saccadic eye movements. Our goal was to characterize the
responses in the vermis using approaches that would allow direct comparisons with
responses of Purkinje cells in another cerebellar area for pursuit, the floccular
complex. Simple-spike firing of vermis Purkinje cells is direction selective
during both pursuit and saccades, but the preferred directions are sufficiently
independent so that downstream circuits could decode signals to drive pursuit and
saccades separately. Complex spikes also were direction selective during pursuit,
and almost all Purkinje cells showed a peak in the probability of complex spikes
during the initiation of pursuit in at least one direction. Unlike the floccular
complex, the preferred directions for simple spikes and complex spikes were not
opposite. The kinematics of smooth eye movement described the simple-spike
responses of vermis Purkinje cells well. Sensitivities were similar to those in
the floccular complex for eye position and considerably lower for eye velocity
and acceleration. The kinematic relations were quite different for saccades vs.
pursuit, supporting the idea that the contributions from the vermis to each kind
of movement could contribute independently in downstream areas. Finally, neither
the complex-spike nor the simple-spike responses of vermis Purkinje cells were
appropriate to support direction learning in pursuit. Complex spikes were not
triggered reliably by an instructive change in target direction; simple-spike
responses showed very small amounts of learning. We conclude that the vermis
plays a different role in pursuit eye movements compared with the floccular
complex.NEW & NOTEWORTHY The midline oculomotor cerebellum plays a different role
in smooth pursuit eye movements compared with the lateral, floccular complex and
appears to be much less involved in direction learning in pursuit. The output
from the oculomotor vermis during pursuit lies along a null-axis for saccades and
vice versa. Thus the vermis can play independent roles in the two kinds of eye
movement.
PMID- 28515288
TI - Motor recovery beginning 23 years after ischemic stroke.
AB - It is widely believed that most stroke recovery occurs within 6 mo, with little
benefit of physiotherapy or other modalities beyond 1 yr. We report a remarkable
case of stroke recovery beginning 23 yr after a severe stroke due to embolization
from the innominate artery and subclavian artery, resulting from compression of
the right subclavian artery by a cervical rib. The patient had a large right
frontoparietal infarction with severe left hemiparesis and a totally
nonfunctional spastic left hand. He experienced some recovery of hand function
that began 23 yr after the stroke, 1 yr after he took up regular swimming. As a
result, intensive physiotherapy was initiated, with repetitive large muscle
movement and a spring-loaded mechanical orthosis that provides resistance to
finger flexors and supports finger extensors. Within 2 yr, he could pick up coins
with the previously useless left hand. Functional MRI studies document widespread
distribution of the recovery in both hemispheres. This case provides impetus not
only to more intensive and prolonged physiotherapy, but also to treatment with
emerging modalities such as stem cell therapy and exosome and microRNA
therapies.NEW & NOTEWORTHY Widespread bilateral activation of both sides of the
cerebrum and cerebellum are demonstrated on functional MRI after motor recovery
of a completely nonfunctional left hand that began 23 yr after a severe stroke.
This suggests that the generally accepted window of recovery beyond which further
therapy is not indicated should be entirely reconsidered. Physiotherapy and new
modalities in development might be indicated long after a stroke.
PMID- 28515287
TI - Context effects on smooth pursuit and manual interception of a disappearing
target.
AB - In our natural environment, we interact with moving objects that are surrounded
by richly textured, dynamic visual contexts. Yet most laboratory studies on
vision and movement show visual objects in front of uniform gray backgrounds.
Context effects on eye movements have been widely studied, but it is less well
known how visual contexts affect hand movements. Here we ask whether eye and hand
movements integrate motion signals from target and context similarly or
differently, and whether context effects on eye and hand change over time. We
developed a track-intercept task requiring participants to track the initial
launch of a moving object ("ball") with smooth pursuit eye movements. The ball
disappeared after a brief presentation, and participants had to intercept it in a
designated "hit zone." In two experiments (n = 18 human observers each), the ball
was shown in front of a uniform or a textured background that either was
stationary or moved along with the target. Eye and hand movement latencies and
speeds were similarly affected by the visual context, but eye and hand
interception (eye position at time of interception, and hand interception timing
error) did not differ significantly between context conditions. Eye and hand
interception timing errors were strongly correlated on a trial-by-trial basis
across all context conditions, highlighting the close relation between these
responses in manual interception tasks. Our results indicate that visual contexts
similarly affect eye and hand movements but that these effects may be short
lasting, affecting movement trajectories more than movement end points.NEW &
NOTEWORTHY In a novel track-intercept paradigm, human observers tracked a briefly
shown object moving across a textured, dynamic context and intercepted it with
their finger after it had disappeared. Context motion significantly affected eye
and hand movement latency and speed, but not interception accuracy; eye and hand
position at interception were correlated on a trial-by-trial basis. Visual
context effects may be short-lasting, affecting movement trajectories more than
movement end points.
PMID- 28515289
TI - Learning temporal context shapes prestimulus alpha oscillations and improves
visual discrimination performance.
AB - Time is an inseparable component of every physical event that we perceive, yet it
is not clear how the brain processes time or how the neuronal representation of
time affects our perception of events. Here we asked subjects to perform a visual
discrimination task while we changed the temporal context in which the stimuli
were presented. We collected electroencephalography (EEG) signals in two temporal
contexts. In predictable blocks stimuli were presented after a constant delay
relative to a visual cue, and in unpredictable blocks stimuli were presented
after variable delays relative to the visual cue. Four subsecond delays of 83,
150, 400, and 800 ms were used in the predictable and unpredictable blocks. We
observed that predictability modulated the power of prestimulus alpha
oscillations in the parieto-occipital sites: alpha power increased in the 300-ms
window before stimulus onset in the predictable blocks compared with the
unpredictable blocks. This modulation only occurred in the longest delay period,
800 ms, in which predictability also improved the behavioral performance of the
subjects. Moreover, learning the temporal context shaped the prestimulus alpha
power: modulation of prestimulus alpha power grew during the predictable block
and correlated with performance enhancement. These results suggest that the brain
is able to learn the subsecond temporal context of stimuli and use this to
enhance sensory processing. Furthermore, the neural correlate of this temporal
prediction is reflected in the alpha oscillations.NEW & NOTEWORTHY It is not well
understood how the uncertainty in the timing of an external event affects its
processing, particularly at subsecond scales. Here we demonstrate how a
predictable timing scheme improves visual processing. We found that learning the
predictable scheme gradually shaped the prestimulus alpha power. These findings
indicate that the human brain is able to extract implicit subsecond patterns in
the temporal context of events.
PMID- 28515290
TI - A Point Mutation in the Rhesus Rotavirus VP4 Protein Generated through a
Rotavirus Reverse Genetics System Attenuates Biliary Atresia in the Murine Model.
AB - Rotavirus infection is one of the most common causes of diarrheal illness in
humans. In neonatal mice, rhesus rotavirus (RRV) can induce biliary atresia (BA),
a disease resulting in inflammatory obstruction of the extrahepatic biliary tract
and intrahepatic bile ducts. We previously showed that the amino acid arginine
(R) within the sequence SRL (amino acids 445 to 447) in the RRV VP4 protein is
required for viral binding and entry into biliary epithelial cells. To determine
if this single amino acid (R) influences the pathogenicity of the virus, we
generated a recombinant virus with a single amino acid mutation at this site
through a reverse genetics system. We demonstrated that the RRV mutant (RRVVP4
R446G) produced less symptomatology and replicated to lower titers both in vivo
and in vitro than those seen with wild-type RRV, with reduced binding in
cholangiocytes. Our results demonstrate that a single amino acid change in the
RRV VP4 gene influences cholangiocyte tropism and reduces pathogenicity in
mice.IMPORTANCE Rotavirus is the leading cause of diarrhea in humans. Rhesus
rotavirus (RRV) can also lead to biliary atresia (a neonatal human disease) in
mice. We developed a reverse genetics system to create a mutant of RRV (RRVVP4
R446G) with a single amino acid change in the VP4 protein compared to that of
wild-type RRV. In vitro, the mutant virus had reduced binding and infectivity in
cholangiocytes. In vivo, it produced fewer symptoms and lower mortality in
neonatal mice, resulting in an attenuated form of biliary atresia.
PMID- 28515291
TI - Differential Disease Susceptibilities in Experimentally Reptarenavirus-Infected
Boa Constrictors and Ball Pythons.
AB - Inclusion body disease (IBD) is an infectious disease originally described in
captive snakes. It has traditionally been diagnosed by the presence of large
eosinophilic cytoplasmic inclusions and is associated with neurological,
gastrointestinal, and lymphoproliferative disorders. Previously, we identified
and established a culture system for a novel lineage of arenaviruses isolated
from boa constrictors diagnosed with IBD. Although ample circumstantial evidence
suggested that these viruses, now known as reptarenaviruses, cause IBD, there has
been no formal demonstration of disease causality since their discovery. We
therefore conducted a long-term challenge experiment to test the hypothesis that
reptarenaviruses cause IBD. We infected boa constrictors and ball pythons by
cardiac injection of purified virus. We monitored the progression of viral growth
in tissues, blood, and environmental samples. Infection produced dramatically
different disease outcomes in snakes of the two species. Ball pythons infected
with Golden Gate virus (GoGV) and with another reptarenavirus displayed severe
neurological signs within 2 months, and viral replication was detected only in
central nervous system tissues. In contrast, GoGV-infected boa constrictors
remained free of clinical signs for 2 years, despite high viral loads and the
accumulation of large intracellular inclusions in multiple tissues, including the
brain. Inflammation was associated with infection in ball pythons but not in boa
constrictors. Thus, reptarenavirus infection produces inclusions and inclusion
body disease, although inclusions per se are neither necessarily associated with
nor required for disease. Although the natural distribution of reptarenaviruses
has yet to be described, the different outcomes of infection may reflect
differences in geographical origin.IMPORTANCE New DNA sequencing technologies
have made it easier than ever to identify the sequences of microorganisms in
diseased tissues, i.e., to identify organisms that appear to cause disease, but
to be certain that a candidate pathogen actually causes disease, it is necessary
to provide additional evidence of causality. We have done this to demonstrate
that reptarenaviruses cause inclusion body disease (IBD), a serious transmissible
disease of snakes. We infected boa constrictors and ball pythons with purified
reptarenavirus. Ball pythons fell ill within 2 months of infection and displayed
signs of neurological disease typical of IBD. In contrast, boa constrictors
remained healthy over 2 years, despite high levels of virus throughout their
bodies. This difference matches previous reports that pythons are more
susceptible to IBD than boas and could reflect the possibility that boas are
natural hosts of these viruses in the wild.
PMID- 28515292
TI - Molluscum Contagiosum Virus MC159 Abrogates cIAP1-NEMO Interactions and Inhibits
NEMO Polyubiquitination.
AB - Molluscum contagiosum virus (MCV) is a dermatotropic poxvirus that causes benign
skin lesions. MCV lesions persist because of virally encoded immune evasion
molecules that inhibit antiviral responses. The MCV MC159 protein suppresses NF
kappaB activation, a powerful antiviral response, via interactions with the NF
kappaB essential modulator (NEMO) subunit of the IkappaB kinase (IKK) complex.
Binding of MC159 to NEMO does not disrupt the IKK complex, implying that MC159
prevents IKK activation via an as-yet-unidentified strategy. Here, we
demonstrated that MC159 inhibited NEMO polyubiquitination, a posttranslational
modification required for IKK and downstream NF-kappaB activation. Because MCV
cannot be propagated in cell culture, MC159 was expressed independent of
infection or during a surrogate vaccinia virus infection to identify how MC159
prevented polyubiquitination. Cellular inhibitor of apoptosis protein 1 (cIAP1)
is a cellular E3 ligase that ubiquitinates NEMO. Mutational analyses revealed
that MC159 and cIAP1 each bind to the same NEMO region, suggesting that MC159 may
competitively inhibit cIAP1-NEMO interactions. Indeed, MC159 prevented cIAP1-NEMO
interactions. MC159 also diminished cIAP1-mediated NEMO polyubiquitination and
cIAP1-induced NF-kappaB activation. These data suggest that MC159 competitively
binds to NEMO to prevent cIAP1-induced NEMO polyubiquitination. To our knowledge,
this is the first report of a viral protein disrupting NEMO-cIAP1 interactions to
strategically suppress IKK activation. All viruses must antagonize antiviral
signaling events for survival. We hypothesize that MC159 inhibits NEMO
polyubiquitination as a clever strategy to manipulate the host cell environment
to the benefit of the virus.IMPORTANCE Molluscum contagiosum virus (MCV) is a
human-specific poxvirus that causes persistent skin neoplasms. The persistence of
MCV has been attributed to viral downregulation of host cell immune responses
such as NF-kappaB activation. We show here that the MCV MC159 protein interacts
with the NEMO subunit of the IKK complex to prevent NEMO interactions with the
cIAP1 E3 ubiquitin ligase. This interaction correlates with a dampening of cIAP1
to polyubiquitinate NEMO and to activate NF-kappaB. This inhibition of cIAP1-NEMO
interactions is a new viral strategy to minimize IKK activation and to control
NEMO polyubiquitination. This research provides new insights into mechanisms that
persistent viruses may use to cause long-term infection of host cells.
PMID- 28515293
TI - Virus-Like Vesicles of Kaposi's Sarcoma-Associated Herpesvirus Activate Lytic
Replication by Triggering Differentiation Signaling.
AB - Virus-like vesicles (VLVs) are membrane-enclosed vesicles that resemble native
enveloped viruses in organization but lack the viral capsid and genome. During
the productive infection of tumor-associated gammaherpesviruses, both virions and
VLVs are produced and are released into the extracellular space. However, studies
of gammaherpesvirus-associated VLVs have been largely restricted by the technical
difficulty of separating VLVs from mature virions. Here we report a strategy of
selectively isolating VLVs by using a Kaposi's sarcoma-associated herpesvirus
(KSHV) mutant that is defective in small capsid protein and is unable to produce
mature virions. Using mass spectrometry analysis, we found that VLVs contained
viral glycoproteins required for cellular entry, as well as tegument proteins
involved in regulating lytic replication, but lacked capsid proteins. Functional
analysis showed that VLVs induced the expression of the viral lytic activator
RTA, initiating KSHV lytic gene expression. Furthermore, employing RNA
sequencing, we performed a genomewide analysis of cellular responses triggered by
VLVs and found that PRDM1, a master regulator in cell differentiation, was
significantly upregulated. In the context of KSHV replication, we demonstrated
that VLV-induced upregulation of PRDM1 was necessary and sufficient to reactivate
KSHV by activating its RTA promoter. In sum, our study systematically examined
the composition of VLVs and demonstrated their biological roles in manipulating
host cell responses and facilitating KSHV lytic replication.IMPORTANCE Cells
lytically infected with tumor-associated herpesviruses produce a high proportion
of virus-like vesicles (VLVs). The composition and function of VLVs have not been
well defined, largely due to the inability to efficiently isolate VLVs that are
free of virions. Using a cell system capable of establishing latent KSHV
infection and robust reactivation, we successfully isolated VLVs from a KSHV
mutant defective in the small capsid protein. We quantitatively analyzed proteins
and microRNAs in VLVs and characterized the roles of VLVs in manipulating host
cells and facilitating viral infection. More importantly, we demonstrated that by
upregulating PRDM1 expression, VLVs triggered differentiation signaling in
targeted cells and facilitated viral lytic infection via activation of the RTA
promoter. Our study not only demonstrates a new strategy for isolating VLVs but
also shows the important roles of KSHV-associated VLVs in intercellular
communication and the viral life cycle.
PMID- 28515294
TI - Deletion of the Vaccinia Virus B1 Kinase Reveals Essential Functions of This
Enzyme Complemented Partly by the Homologous Cellular Kinase VRK2.
AB - The vaccinia virus B1 kinase is highly conserved among poxviruses and is
essential for the viral life cycle. B1 exhibits a remarkable degree of similarity
to vaccinia virus-related kinases (VRKs), a family of cellular kinases,
suggesting that the viral enzyme has evolved to mimic VRK activity. Indeed, B1
and VRKs have been demonstrated to target a shared substrate, the DNA binding
protein BAF, elucidating a signaling pathway important for both mitosis and the
antiviral response. In this study, we further characterize the role of B1 during
vaccinia infection to gain novel insights into its regulation and integration
with cellular signaling pathways. We begin by describing the construction and
characterization of the first B1 deletion virus (vvDeltaB1) produced using a
complementing cell line expressing the viral kinase. Examination of vvDeltaB1
revealed that B1 is critical for the production of infectious virions in various
cell types and is sufficient for BAF phosphorylation. Interestingly, the severity
of the defect in DNA replication following the loss of B1 varied between cell
types, leading us to posit that cellular VRKs partly complement for the absence
of B1 in some cell lines. Using cell lines devoid of either VRK1 or VRK2, we
tested this hypothesis and discovered that VRK2 expression facilitates DNA
replication and allows later stages of the viral life cycle to proceed in the
absence of B1. Finally, we present evidence that the impact of VRK2 on vaccinia
virus is largely independent of BAF phosphorylation. These data support a model
in which B1 and VRK2 share additional substrates important for the replication of
cytoplasmic poxviruses.IMPORTANCE Viral mimicry of cellular signaling modulators
provides clear evidence that the pathogen targets an important host pathway
during infection. Poxviruses employ numerous viral homologs of cellular proteins,
the study of which have yielded insights into signaling pathways used by both
virus and cells alike. The vaccinia virus B1 protein is a homolog of cellular
vaccinia virus-related kinases (VRKs) and is needed for viral DNA replication and
likely other stages of the viral life cycle. However, much remains to be learned
about how B1 and VRKs overlap functionally. This study utilizes new tools,
including a B1 deletion virus and VRK knockout cells, to further characterize the
functional links between the viral and cellular enzymes. As a result, we have
discovered that B1 and VRK2 target a common set of substrates vital to productive
infection of this large cytoplasmic DNA virus.
PMID- 28515295
TI - Natural Variation of Epstein-Barr Virus Genes, Proteins, and Primary MicroRNA.
AB - Viral gene sequences from an enlarged set of about 200 Epstein-Barr virus (EBV)
strains, including many primary isolates, have been used to investigate variation
in key viral genetic regions, particularly LMP1, Zp, gp350, EBNA1, and the BART
microRNA (miRNA) cluster 2. Determination of type 1 and type 2 EBV in saliva
samples from people from a wide range of geographic and ethnic backgrounds
demonstrates a small percentage of healthy white Caucasian British people
carrying predominantly type 2 EBV. Linkage of Zp and gp350 variants to type 2 EBV
is likely to be due to their genes being adjacent to the EBNA3 locus, which is
one of the major determinants of the type 1/type 2 distinction. A novel
classification of EBNA1 DNA binding domains, named QCIGP, results from phylogeny
analysis of their protein sequences but is not linked to the type 1/type 2
classification. The BART cluster 2 miRNA region is classified into three major
variants through single-nucleotide polymorphisms (SNPs) in the primary miRNA
outside the mature miRNA sequences. These SNPs can result in altered levels of
expression of some miRNAs from the BART variant frequently present in Chinese and
Indonesian nasopharyngeal carcinoma (NPC) samples. The EBV genetic variants
identified here provide a basis for future, more directed analysis of association
of specific EBV variations with EBV biology and EBV-associated
diseases.IMPORTANCE Incidence of diseases associated with EBV varies greatly in
different parts of the world. Thus, relationships between EBV genome sequence
variation and health, disease, geography, and ethnicity of the host may be
important for understanding the role of EBV in diseases and for development of an
effective EBV vaccine. This paper provides the most comprehensive analysis so far
of variation in specific EBV genes relevant to these diseases and proposed EBV
vaccines. By focusing on variation in LMP1, Zp, gp350, EBNA1, and the BART miRNA
cluster 2, new relationships with the known type 1/type 2 strains are
demonstrated, and a novel classification of EBNA1 and the BART miRNAs is
proposed.
PMID- 28515296
TI - Hepatitis C Virus Lipoviroparticles Assemble in the Endoplasmic Reticulum (ER)
and Bud off from the ER to the Golgi Compartment in COPII Vesicles.
AB - Hepatitis C virus (HCV) exists as a lipoprotein-virus hybrid lipoviroparticle
(LVP). In vitro studies have demonstrated the importance of apolipoproteins in
HCV secretion and infectivity, leading to the notion that HCV coopts the
secretion of very-low-density lipoprotein (VLDL) for its egress. However, the
mechanisms involved in virus particle assembly and egress are still elusive. The
biogenesis of VLDL particles occurs in the endoplasmic reticulum (ER), followed
by subsequent lipidation in the ER and Golgi compartment. The secretion of mature
VLDL particles occurs through the Golgi secretory pathway. HCV virions are
believed to latch onto or fuse with the nascent VLDL particle in either the ER or
the Golgi compartment, resulting in the generation of LVPs. In our attempt to
unravel the collaboration between HCV and VLDL secretion, we studied HCV
particles budding from the ER en route to the Golgi compartment in COPII
vesicles. Biophysical characterization of COPII vesicles fractionated on an
iodixanol gradient revealed that HCV RNA is enriched in the highly buoyant COPII
vesicle fractions and cofractionates with apolipoprotein B (ApoB), ApoE, and the
HCV core and envelope proteins. Electron microscopy of immunogold-labeled
microsections revealed that the HCV envelope and core proteins colocalize with
apolipoproteins and HCV RNA in Sec31-coated COPII vesicles. Ultrastructural
analysis also revealed the presence of HCV structural proteins, RNA, and
apolipoproteins in the Golgi stacks. These findings support the hypothesis that
HCV LVPs assemble in the ER and are transported to the Golgi compartment in COPII
vesicles to embark on the Golgi secretory route.IMPORTANCE HCV assembly and
release accompany the formation of LVPs that circulate in the sera of HCV
patients and are also produced in an in vitro culture system. The pathway of HCV
morphogenesis and secretion has not been fully understood. This study
investigates the exact site where the association of HCV virions with host
lipoproteins occurs. Using immunoprecipitation of COPII vesicles and immunogold
electron microscopy (EM), we characterize the existence of LVPs that
cofractionate with lipoproteins, viral proteins, RNA, and vesicular components.
Our results show that this assembly occurs in the ER, and LVPs thus formed are
carried through the Golgi network by vesicular transport. This work provides a
unique insight into the HCV LVP assembly process within infected cells and offers
opportunities for designing antiviral therapeutic cellular targets.
PMID- 28515297
TI - Attenuation of Foot-and-Mouth Disease Virus by Engineered Viral Polymerase
Fidelity.
AB - Foot-and-mouth disease virus (FMDV) RNA-dependent RNA polymerase (RdRp) (3Dpol)
catalyzes viral RNA synthesis. Its characteristic low fidelity and absence of
proofreading activity allow FMDV to rapidly mutate and adapt to dynamic
environments. In this study, we used the structure of FMDV 3Dpol in combination
with previously reported results from similar picornaviral polymerases to design
point mutations that would alter replication fidelity. In particular, we targeted
Trp237 within conserved polymerase motif A because of the low reversion potential
inherent in the single UGG codon. Using biochemical and genetic tools, we show
that the replacement of tryptophan 237 with phenylalanine imparts higher
fidelity, but replacements with isoleucine and leucine resulted in lower-fidelity
phenotypes. Viruses containing these W237 substitutions show in vitro growth
kinetics and plaque morphologies similar to those of the wild-type (WT) A24
Cruzeiro strain in BHK cells, and both high- and low-fidelity variants retained
fitness during coinfection with the wild-type virus. The higher-fidelity W237F
(W237FHF) mutant virus was more resistant to the mutagenic nucleoside analogs
ribavirin and 5-fluorouracil than the WT virus, whereas the lower-fidelity W237I
(W237ILF) and W237LLF mutant viruses exhibited lower ribavirin resistance.
Interestingly, the variant viruses showed heterogeneous and slightly delayed
growth kinetics in primary porcine kidney cells, and they were significantly
attenuated in mouse infection experiments. These data demonstrate, for a single
virus, that either increased or decreased RdRp fidelity attenuates virus growth
in animals, which is a desirable feature for the development of safer and
genetically more stable vaccine candidates.IMPORTANCE Foot-and-mouth disease
(FMD) is the most devastating disease affecting livestock worldwide. Here, using
structural and biochemical analyses, we have identified FMDV 3Dpol mutations that
affect polymerase fidelity. Recombinant FMDVs containing substitutions at 3Dpol
tryptophan residue 237 were genetically stable and displayed plaque phenotypes
and growth kinetics similar to those of the wild-type virus in cell culture. We
further demonstrate that viruses harboring either a W237FHF substitution or
W237ILF and W237LLF mutations were highly attenuated in animals. Our study shows
that obtaining 3Dpol fidelity variants by protein engineering based on polymerase
structure and function could be exploited for the development of attenuated FMDV
vaccine candidates that are safer and more stable than strains obtained by
selective pressure via mutagenic nucleotides or adaptation approaches.
PMID- 28515298
TI - Crimean-Congo Hemorrhagic Fever Virus Nucleocapsid Protein Augments mRNA
Translation.
AB - Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne Nairovirus of the
Bunyaviridae family, causing severe illness with high mortality rates in humans.
Here, we demonstrate that CCHFV nucleocapsid protein (CCHFV-NP) augments mRNA
translation. CCHFV-NP binds to the viral mRNA 5' untranslated region (UTR) with
high affinity. It facilitates the translation of reporter mRNA both in vivo and
in vitro with the assistance of the viral mRNA 5' UTR. CCHFV-NP equally favors
the translation of both capped and uncapped mRNAs, demonstrating the independence
of this translation strategy on the 5' cap. Unlike the canonical host translation
machinery, inhibition of eIF4F complex, an amalgam of three initiation factors,
eIF4A, eIF4G, and eIF4E, by the chemical inhibitor 4E1RCat did not impact the
CCHFV-NP-mediated translation mechanism. However, the proteolytic degradation of
eIF4G alone by the human rhinovirus 2A protease abrogated this translation
strategy. Our results demonstrate that eIF4F complex formation is not required
but eIF4G plays a critical role in this translation mechanism. Our results
suggest that CCHFV has adopted a unique translation mechanism to facilitate the
translation of viral mRNAs in the host cell cytoplasm where cellular transcripts
are competing for the same translation apparatus.IMPORTANCE Crimean-Congo
hemorrhagic fever, a highly contagious viral disease endemic to more than 30
countries, has limited treatment options. Our results demonstrate that NP favors
the translation of a reporter mRNA harboring the viral mRNA 5' UTR. It is highly
likely that CCHFV uses an NP-mediated translation strategy for the rapid
synthesis of viral proteins during the course of infection. Shutdown of this
translation mechanism might selectively impact viral protein synthesis,
suggesting that an NP-mediated translation strategy is a target for therapeutic
intervention against this viral disease.
PMID- 28515299
TI - A Diverse Range of Novel RNA Viruses in Geographically Distinct Honey Bee
Populations.
AB - Understanding the diversity and consequences of viruses present in honey bees is
critical for maintaining pollinator health and managing the spread of disease.
The viral landscape of honey bees (Apis mellifera) has changed dramatically since
the emergence of the parasitic mite Varroa destructor, which increased the spread
of virulent variants of viruses such as deformed wing virus. Previous genomic
studies have focused on colonies suffering from infections by Varroa and virulent
viruses, which could mask other viral species present in honey bees, resulting in
a distorted view of viral diversity. To capture the viral diversity within
colonies that are exposed to mites but do not suffer the ultimate consequences of
the infestation, we examined populations of honey bees that have evolved
naturally or have been selected for resistance to Varroa This analysis revealed
seven novel viruses isolated from honey bees sampled globally, including the
first identification of negative-sense RNA viruses in honey bees. Notably, two
rhabdoviruses were present in three geographically diverse locations and were
also present in Varroa mites parasitizing the bees. To characterize the antiviral
response, we performed deep sequencing of small RNA populations in honey bees and
mites. This provided evidence of a Dicer-mediated immune response in honey bees,
while the viral small RNA profile in Varroa mites was novel and distinct from the
response observed in bees. Overall, we show that viral diversity in honey bee
colonies is greater than previously thought, which encourages additional studies
of the bee virome on a global scale and which may ultimately improve disease
management.IMPORTANCE Honey bee populations have become increasingly susceptible
to colony losses due to pathogenic viruses spread by parasitic Varroa mites. To
date, 24 viruses have been described in honey bees, with most belonging to the
order Picornavirales Collapsing Varroa-infected colonies are often overwhelmed
with high levels of picornaviruses. To examine the underlying viral diversity in
honey bees, we employed viral metatranscriptomics analyses on three
geographically diverse Varroa-resistant populations from Europe, Africa, and the
Pacific. We describe seven novel viruses from a range of diverse viral families,
including two viruses that are present in all three locations. In honey bees,
small RNA sequences indicate that these viruses are processed by Dicer and the
RNA interference pathway, whereas Varroa mites produce strikingly novel small RNA
patterns. This work increases the number and diversity of known honey bee viruses
and will ultimately contribute to improved disease management in our most
important agricultural pollinator.
PMID- 28515300
TI - A Novel A(H7N2) Influenza Virus Isolated from a Veterinarian Caring for Cats in a
New York City Animal Shelter Causes Mild Disease and Transmits Poorly in the
Ferret Model.
AB - In December 2016, a low-pathogenic avian influenza (LPAI) A(H7N2) virus was
identified to be the causative source of an outbreak in a cat shelter in New York
City, which subsequently spread to multiple shelters in the states of New York
and Pennsylvania. One person with occupational exposure to infected cats became
infected with the virus, representing the first LPAI H7N2 virus infection in a
human in North America since 2003. Considering the close contact that frequently
occurs between companion animals and humans, it was critical to assess the
relative risk of this novel virus to public health. The virus isolated from the
human case, A/New York/108/2016 (NY/108), caused mild and transient illness in
ferrets and mice but did not transmit to naive cohoused ferrets following
traditional or aerosol-based inoculation methods. The environmental persistence
of NY/108 virus was generally comparable to that of other LPAI H7N2 viruses.
However, NY/108 virus replicated in human bronchial epithelial cells with an
increased efficiency compared with that of previously isolated H7N2 viruses.
Furthermore, the novel H7N2 virus was found to utilize a relatively lower pH for
hemagglutinin activation, similar to human influenza viruses. Our data suggest
that the LPAI H7N2 virus requires further adaptation before representing a
substantial threat to public health. However, the reemergence of an LPAI H7N2
virus in the northeastern United States underscores the need for continuous
surveillance of emerging zoonotic influenza viruses inclusive of mammalian
species, such as domestic felines, that are not commonly considered intermediate
hosts for avian influenza viruses.IMPORTANCE Avian influenza viruses are capable
of crossing the species barrier to infect mammals, an event of public health
concern due to the potential acquisition of a pandemic phenotype. In December
2016, an H7N2 virus caused an outbreak in cats in multiple animal shelters in New
York State. This was the first detection of this virus in the northeastern United
States in over a decade and the first documented infection of a felid with an
H7N2 virus. A veterinarian became infected following occupational exposure to
H7N2 virus-infected cats, necessitating the evaluation of this virus for its
capacity to cause disease in mammals. While the H7N2 virus was associated with
mild illness in mice and ferrets and did not spread well between ferrets, it
nonetheless possessed several markers of virulence for mammals. These data
highlight the promiscuity of influenza viruses and the need for diligent
surveillance across multiple species to quickly identify an emerging strain with
pandemic potential.
PMID- 28515301
TI - Influenza A Virus NS1 Protein Promotes Efficient Nuclear Export of Unspliced
Viral M1 mRNA.
AB - Influenza A virus mRNAs are transcribed by the viral RNA-dependent RNA polymerase
in the cell nucleus before being exported to the cytoplasm for translation.
Segment 7 produces two major transcripts: an unspliced mRNA that encodes the M1
matrix protein and a spliced transcript that encodes the M2 ion channel. Export
of both mRNAs is dependent on the cellular NXF1/TAP pathway, but it is unclear
how they are recruited to the export machinery or how the intron-containing but
unspliced M1 mRNA bypasses the normal quality-control checkpoints. Using
fluorescent in situ hybridization to monitor segment 7 mRNA localization, we
found that cytoplasmic accumulation of unspliced M1 mRNA was inefficient in the
absence of NS1, both in the context of segment 7 RNPs reconstituted by plasmid
transfection and in mutant virus-infected cells. This effect was independent of
any major effect on steady-state levels of segment 7 mRNA or splicing but
corresponded to a ~5-fold reduction in the accumulation of M1. A similar defect
in intronless hemagglutinin (HA) mRNA nuclear export was seen with an NS1 mutant
virus. Efficient export of M1 mRNA required both an intact NS1 RNA-binding domain
and effector domain. Furthermore, while wild-type NS1 interacted with cellular
NXF1 and also increased the interaction of segment 7 mRNA with NXF1, mutant NS1
polypeptides unable to promote mRNA export did neither. Thus, we propose that NS1
facilitates late viral gene expression by acting as an adaptor between viral
mRNAs and the cellular nuclear export machinery to promote their nuclear
export.IMPORTANCE Influenza A virus is a major pathogen of a wide variety of
mammalian and avian species that threatens public health and food security. A
fuller understanding of the virus life cycle is important to aid control
strategies. The virus has a small genome that encodes relatively few proteins
that are often multifunctional. Here, we characterize a new function for the NS1
protein, showing that, as well as previously identified roles in antagonizing the
innate immune defenses of the cell and directly upregulating translation of viral
mRNAs, it also promotes the nuclear export of the viral late gene mRNAs by acting
as an adaptor between the viral mRNAs and the cellular mRNA nuclear export
machinery.
PMID- 28515302
TI - Transposon Mutagenesis of the Zika Virus Genome Highlights Regions Essential for
RNA Replication and Restricted for Immune Evasion.
AB - The molecular constraints affecting Zika virus (ZIKV) evolution are not well
understood. To investigate ZIKV genetic flexibility, we used transposon
mutagenesis to add 15-nucleotide insertions throughout the ZIKV MR766 genome and
subsequently deep sequenced the viable mutants. Few ZIKV insertion mutants
replicated, which likely reflects a high degree of functional constraints on the
genome. The NS1 gene exhibited distinct mutational tolerances at different stages
of the screen. This result may define regions of the NS1 protein that are
required for the different stages of the viral life cycle. The ZIKV structural
genes showed the highest degree of insertional tolerance. Although the envelope
(E) protein exhibited particular flexibility, the highly conserved envelope
domain II (EDII) fusion loop of the E protein was intolerant of transposon
insertions. The fusion loop is also a target of pan-flavivirus antibodies that
are generated against other flaviviruses and neutralize a broad range of dengue
virus and ZIKV isolates. The genetic restrictions identified within the epitopes
in the EDII fusion loop likely explain the sequence and antigenic conservation of
these regions in ZIKV and among multiple flaviviruses. Thus, our results provide
insights into the genetic restrictions on ZIKV that may affect the evolution of
this virus.IMPORTANCE Zika virus recently emerged as a significant human
pathogen. Determining the genetic constraints on Zika virus is important for
understanding the factors affecting viral evolution. We used a genome-wide
transposon mutagenesis screen to identify where mutations were tolerated in
replicating viruses. We found that the genetic regions involved in RNA
replication were mostly intolerant of mutations. The genes coding for structural
proteins were more permissive to mutations. Despite the flexibility observed in
these regions, we found that epitopes bound by broadly reactive antibodies were
genetically constrained. This finding may explain the genetic conservation of
these epitopes among flaviviruses.
PMID- 28515306
TI - Intermediate-Term Memory as a Bridge between Working and Long-Term Memory.
PMID- 28515304
TI - Reactive Oxygen Species-Mediated c-Jun NH2-Terminal Kinase Activation Contributes
to Hepatitis B Virus X Protein-Induced Autophagy via Regulation of the Beclin
1/Bcl-2 Interaction.
AB - Autophagy is closely associated with the regulation of hepatitis B virus (HBV)
replication. HBV X protein (HBx), a multifunctional regulator in HBV-associated
biological processes, has been demonstrated to be crucial for autophagy induction
by HBV. However, the molecular mechanisms of autophagy induction by HBx,
especially the signaling pathways involved, remain elusive. In the present
investigation, we demonstrated that HBx induced autophagosome formation
independently of the class I phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR
signaling pathway. In contrast, the class III PI3K(VPS34)/beclin-1 pathway was
revealed to be critical for HBx-induced autophagosome formation. Further study
showed that HBx did not affect the level of VPS34 and beclin-1 expression but
inhibited beclin-1/Bcl-2 association, and c-Jun NH2-terminal kinase (JNK)
signaling was found to be important for this process. Moreover, it was found that
HBx treatment led to the generation of reactive oxygen species (ROS), and
inhibition of ROS activity abrogated both JNK activation and autophagosome
formation. Of importance, ROS-JNK signaling was also revealed to play an
important role in HBV-induced autophagosome formation and subsequent HBV
replication. These data may provide deeper insight into the mechanisms of
autophagy induction by HBx and help in the design of new therapeutic strategies
against HBV infection.IMPORTANCE HBx plays a key role in diverse HBV-associated
biological processes, including autophagy induction. However, the molecular
mechanisms of autophagy induction by HBx, especially the signaling pathways
involved, remain elusive. In the present investigation, we found that HBx induced
autophagy independently of the class I PI3K/AKT/mTOR signaling pathway, while the
class III PI3K(VPS34)/beclin-1 pathway was revealed to be crucial for this
process. Further data showed that ROS-JNK activation by HBx resulted in the
release of beclin-1 from its association with Bcl-2 to form a complex with VPS34,
thus enhancing autophagosome formation. Of importance, ROS-JNK signaling was also
demonstrated to be critical for HBV replication via regulation of autophagy
induction. These data help to elucidate the molecular mechanisms of autophagy
induction by HBx/HBV and might be useful for designing novel therapeutic
approaches to HBV infection.
PMID- 28515303
TI - Spontaneous and Vaccine-Induced Clearance of Mus Musculus Papillomavirus 1
Infection.
AB - Mus musculus papillomavirus 1 (MmuPV1/MusPV1) induces persistent papillomas in
immunodeficient mice but not in common laboratory strains. To facilitate the
study of immune control, we sought an outbred and immunocompetent laboratory
mouse strain in which persistent papillomas could be established. We found that
challenge of SKH1 mice (Crl:SKH1-Hrhr) with MmuPV1 by scarification on their tail
resulted in three clinical outcomes: (i) persistent (>2-month) papillomas (~20%);
(ii) transient papillomas that spontaneously regress, typically within 2 months
(~15%); and (iii) no visible papillomas and viral clearance (~65%). SKH1 mice
with persistent papillomas were treated by using a candidate
preventive/therapeutic naked-DNA vaccine that expresses human calreticulin (hCRT)
fused in frame to MmuPV1 E6 (mE6) and mE7 early proteins and residues 11 to 200
of the late protein L2 (hCRTmE6/mE7/mL2). Three intramuscular DNA vaccinations
were delivered biweekly via in vivo electroporation, and both humoral and CD8 T
cell responses were mapped and measured. Previously persistent papillomas
disappeared within 2 months after the final vaccination. Coincident virologic
clearance was confirmed by in situ hybridization and a failure of disease to
recur after CD3 T cell depletion. Vaccination induced strong mE6 and mE7 CD8+ T
cell responses in all mice, although they were significantly weaker in mice that
initially presented with persistent warts than in those that spontaneously
cleared their infection. A human papillomavirus 16 (HPV16)-targeted version of
the DNA vaccine also induced L2 antibodies and protected mice from vaginal
challenge with an HPV16 pseudovirus. Thus, MmuPV1 challenge of SKH1 mice is a
promising model of spontaneous and immunotherapy-directed clearances of HPV
related disease.IMPORTANCE High-risk-type human papillomaviruses (hrHPVs) cause
5% of all cancer cases worldwide, notably cervical, anogenital, and oropharyngeal
cancers. Since preventative HPV vaccines have not been widely used in many
countries and do not impact existing infections, there is considerable interest
in the development of therapeutic vaccines to address existing disease and
infections. The strict tropism of HPV requires the use of animal papillomavirus
models for therapeutic vaccine development. However, MmuPV1 failed to grow in
common laboratory strains of mice with an intact immune system. We show that
MmuPV1 challenge of the outbred immunocompetent SKH1 strain produces both
transient and persistent papillomas and that vaccination of the mice with a DNA
expressing an MmuPV1 E6E7L2 fusion with calreticulin can rapidly clear persistent
papillomas. Furthermore, an HPV16-targeted version of the DNA can protect against
vaginal challenge with HPV16, suggesting the promise of this approach to both
prevent and treat papillomavirus-related disease.
PMID- 28515307
TI - Action Organization in Lateral Occipitotemporal Cortex.
PMID- 28515305
TI - Cell Cycle-Dependent Expression of Adeno-Associated Virus 2 (AAV2) Rep in
Coinfections with Herpes Simplex Virus 1 (HSV-1) Gives Rise to a Mosaic of Cells
Replicating either AAV2 or HSV-1.
AB - Adeno-associated virus 2 (AAV2) depends on the simultaneous presence of a helper
virus such as herpes simplex virus 1 (HSV-1) for productive replication. At the
same time, AAV2 efficiently blocks the replication of HSV-1, which would
eventually limit its own replication by diminishing the helper virus reservoir.
This discrepancy begs the question of how AAV2 and HSV-1 can coexist in a cell
population. Here we show that in coinfected cultures, AAV2 DNA replication takes
place almost exclusively in S/G2-phase cells, while HSV-1 DNA replication is
restricted to G1 phase. Live microscopy revealed that not only wild-type AAV2
(wtAAV2) replication but also reporter gene expression from both single-stranded
and double-stranded (self-complementary) recombinant AAV2 vectors preferentially
occurs in S/G2-phase cells, suggesting that the preference for S/G2 phase is
independent of the nature of the viral genome. Interestingly, however, a
substantial proportion of S/G2-phase cells transduced by the double-stranded but
not the single-stranded recombinant AAV2 vectors progressed through mitosis in
the absence of the helper virus. We conclude that cell cycle-dependent AAV2 rep
expression facilitates cell cycle-dependent AAV2 DNA replication and inhibits HSV
1 DNA replication. This may limit competition for cellular and viral helper
factors and, hence, creates a biological niche for either virus to
replicate.IMPORTANCE Adeno-associated virus 2 (AAV2) differs from most other
viruses, as it requires not only a host cell for replication but also a helper
virus such as an adenovirus or a herpesvirus. This situation inevitably leads to
competition for cellular resources. AAV2 has been shown to efficiently inhibit
the replication of helper viruses. Here we present a new facet of the interaction
between AAV2 and one of its helper viruses, herpes simplex virus 1 (HSV-1). We
observed that AAV2 rep gene expression is cell cycle dependent and gives rise to
distinct time-controlled windows for HSV-1 replication. High Rep protein levels
in S/G2 phase support AAV2 replication and inhibit HSV-1 replication. Conversely,
low Rep protein levels in G1 phase permit HSV-1 replication but are insufficient
for AAV2 replication. This allows both viruses to productively replicate in
distinct sets of dividing cells.
PMID- 28515311
TI - Control of Hsp90 chaperone and its clients by N-terminal acetylation and the N
end rule pathway.
AB - We found that the heat shock protein 90 (Hsp90) chaperone system of the yeast
Saccharomyces cerevisiae is greatly impaired in naa10Delta cells, which lack the
NatA Nalpha-terminal acetylase (Nt-acetylase) and therefore cannot N-terminally
acetylate a majority of normally N-terminally acetylated proteins, including
Hsp90 and most of its cochaperones. Chk1, a mitotic checkpoint kinase and a
client of Hsp90, was degraded relatively slowly in wild-type cells but was
rapidly destroyed in naa10Delta cells by the Arg/N-end rule pathway, which
recognized a C terminus-proximal degron of Chk1. Diverse proteins (in addition to
Chk1) that are shown here to be targeted for degradation by the Arg/N-end rule
pathway in naa10Delta cells include Kar4, Tup1, Gpd1, Ste11, and also,
remarkably, the main Hsp90 chaperone (Hsc82) itself. Protection of Chk1 by Hsp90
could be overridden not only by ablation of the NatA Nt-acetylase but also by
overexpression of the Arg/N-end rule pathway in wild-type cells. Split ubiquitin
binding assays detected interactions between Hsp90 and Chk1 in wild-type cells
but not in naa10Delta cells. These and related results revealed a major role of
Nt-acetylation in the Hsp90-mediated protein homeostasis, a strong up-regulation
of the Arg/N-end rule pathway in the absence of NatA, and showed that a number of
Hsp90 clients are previously unknown substrates of the Arg/N-end rule pathway.
PMID- 28515313
TI - Low temperature nullifies the circadian clock in cyanobacteria through Hopf
bifurcation.
AB - Cold temperatures lead to nullification of circadian rhythms in many organisms.
Two typical scenarios explain the disappearance of rhythmicity: the first is
oscillation death, which is the transition from self-sustained oscillation to
damped oscillation that occurs at a critical temperature. The second scenario is
oscillation arrest, in which oscillation terminates at a certain phase. In the
field of nonlinear dynamics, these mechanisms are called the Hopf bifurcation and
the saddle-node on an invariant circle bifurcation, respectively. Although these
mechanisms lead to distinct dynamical properties near the critical temperature,
it is unclear to which scenario the circadian clock belongs. Here we reduced the
temperature to dampen the reconstituted circadian rhythm of phosphorylation of
the recombinant cyanobacterial clock protein KaiC. The data led us to conclude
that Hopf bifurcation occurred at ~19 degrees C. Below this critical
temperature, the self-sustained rhythms of KaiC phosphorylation transformed to
damped oscillations, which are predicted by the Hopf bifurcation theory.
Moreover, we detected resonant oscillations below the critical temperature when
temperature was periodically varied, which was reproduced by numerical
simulations. Our findings suggest that the transition to a damped oscillation
through Hopf bifurcation contributes to maintaining the circadian rhythm of
cyanobacteria through resonance at cold temperatures.
PMID- 28515312
TI - Astrocytic glycogen-derived lactate fuels the brain during exhaustive exercise to
maintain endurance capacity.
AB - Brain glycogen stored in astrocytes provides lactate as an energy source to
neurons through monocarboxylate transporters (MCTs) to maintain neuronal
functions such as hippocampus-regulated memory formation. Although prolonged
exhaustive exercise decreases brain glycogen, the role of this decrease and
lactate transport in the exercising brain remains less clear. Because muscle
glycogen fuels exercising muscles, we hypothesized that astrocytic glycogen plays
an energetic role in the prolonged-exercising brain to maintain endurance
capacity through lactate transport. To test this hypothesis, we used a rat model
of exhaustive exercise and capillary electrophoresis-mass spectrometry-based
metabolomics to observe comprehensive energetics of the brain (cortex and
hippocampus) and muscle (plantaris). At exhaustion, muscle glycogen was depleted
but brain glycogen was only decreased. The levels of MCT2, which takes up lactate
in neurons, increased in the brain, as did muscle MCTs. Metabolomics revealed
that brain, but not muscle, ATP was maintained with lactate and other
glycogenolytic/glycolytic sources. Intracerebroventricular injection of the
glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-d-arabinitol did not
affect peripheral glycemic conditions but suppressed brain lactate production and
decreased hippocampal ATP levels at exhaustion. An MCT2 inhibitor, alpha-cyano-4
hydroxy-cinnamate, triggered a similar response that resulted in lower endurance
capacity. These findings provide direct evidence for the energetic role of
astrocytic glycogen-derived lactate in the exhaustive-exercising brain,
implicating the significance of brain glycogen level in endurance capacity.
Glycogen-maintained ATP in the brain is a possible defense mechanism for neurons
in the exhausted brain.
PMID- 28515314
TI - The mzIdentML Data Standard Version 1.2, Supporting Advances in Proteome
Informatics.
AB - The first stable version of the Proteomics Standards Initiative mzIdentML open
data standard (version 1.1) was published in 2012-capturing the outputs of
peptide and protein identification software. In the intervening years, the
standard has become well-supported in both commercial and open software, as well
as a submission and download format for public repositories. Here we report a new
release of mzIdentML (version 1.2) that is required to keep pace with emerging
practice in proteome informatics. New features have been added to support: (1)
scores associated with localization of modifications on peptides; (2) statistics
performed at the level of peptides; (3) identification of cross-linked peptides;
and (4) support for proteogenomics approaches. In addition, there is now improved
support for the encoding of de novo sequencing of peptides, spectral library
searches, and protein inference. As a key point, the underlying XML schema has
only undergone very minor modifications to simplify as much as possible the
transition from version 1.1 to version 1.2 for implementers, but there have been
several notable updates to the format specification, implementation guidelines,
controlled vocabularies and validation software. mzIdentML 1.2 can be described
as backwards compatible, in that reading software designed for mzIdentML 1.1
should function in most cases without adaptation. We anticipate that these
developments will provide a continued stable base for software teams working to
implement the standard. All the related documentation is accessible at
http://www.psidev.info/mzidentml.
PMID- 28515315
TI - The C-terminal peptide of Aquifex aeolicus riboflavin synthase directs
encapsulation of native and foreign guests by a cage-forming lumazine synthase.
AB - Encapsulation of specific enzymes in self-assembling protein cages is a hallmark
of bacterial compartments that function as counterparts to eukaryotic organelles.
The cage-forming enzyme lumazine synthase (LS) from Bacillus subtilis (BsLS), for
example, encapsulates riboflavin synthase (BsRS), enabling channeling of lumazine
from the site of its generation to the site of its conversion to vitamin B2
Elucidating the molecular mechanisms underlying the assembly of these
supramolecular complexes could help inform new approaches for metabolic
engineering, nanotechnology, and drug delivery. To that end, we investigated a
thermostable LS from Aquifex aeolicus (AaLS) and found that it also forms cage
complexes with the cognate riboflavin synthase (AaRS) when both proteins are co
produced in the cytosol of Escherichia coli A 12-amino acid-long peptide at the C
terminus of AaRS serves as a specific localization sequence responsible for
targeting the guest to the protein compartment. Sequence comparisons suggested
that analogous peptide segments likely direct RS complexation by LS cages in
other bacterial species. Covalent fusion of this peptide tag to heterologous
guest molecules led to their internalization into AaLS assemblies both in vivo
and in vitro, providing a firm foundation for creating tailored biomimetic
nanocompartments for medical and biotechnological applications.
PMID- 28515317
TI - Characterization of a secretory hydrolase from Mycobacterium tuberculosis sheds
critical insight into host lipid utilization by M. tuberculosis.
AB - Mycobacterium tuberculosis causes tuberculosis in humans and predominantly
infects alveolar macrophages. To survive inside host lesions and to evade immune
surveillance, this pathogen has developed many strategies. For example, M.
tuberculosis uses host-derived lipids/fatty acids as nutrients for prolonged
persistence within hypoxic host microenvironments. M. tuberculosis imports these
metabolites through its respective transporters, and in the case of host fatty
acids, a pertinent question arises: does M. tuberculosis have the enzyme(s) for
cleavage of fatty acids from host lipids? We show herein that a previously
uncharacterized membrane-associated M. tuberculosis protein encoded by Rv2672 is
conserved exclusively in actinomycetes, exhibits both lipase and protease
activities, is secreted into macrophages, and catalyzes host lipid hydrolysis. In
light of these functions, we annotated Rv2672 as mycobacterial secreted hydrolase
1 (Msh1). Furthermore, we found that this enzyme is up-regulated both in an in
vitro model of hypoxic stress and in a mouse model of M. tuberculosis infection,
suggesting that the pathogen requires Msh1 under hypoxic conditions. Silencing
Msh1 expression compromised the ability of M. tuberculosis to proliferate inside
lipid-rich foamy macrophages but not under regular culture conditions in vitro,
underscoring Msh1's importance for M. tuberculosis persistence in lipid-rich
microenvironments. Of note, this is the first report providing insight into the
mechanism of host lipid catabolism by an M. tuberculosis enzyme, augmenting our
current understanding of how M. tuberculosis meets its nutrient requirements
under hypoxic conditions.
PMID- 28515316
TI - DNA-damage-induced degradation of EXO1 exonuclease limits DNA end resection to
ensure accurate DNA repair.
AB - End resection of DNA double-strand breaks (DSBs) to generate 3'-single-stranded
DNA facilitates DSB repair via error-free homologous recombination (HR) while
stymieing repair by the error-prone non-homologous end joining (NHEJ) pathway.
Activation of DNA end resection involves phosphorylation of the 5' to 3'
exonuclease EXO1 by the phosphoinositide 3-kinase-like kinases ATM (ataxia
telangiectasia-mutated) and ATR (ATM and Rad3-related) and by the cyclin
dependent kinases 1 and 2. After activation, EXO1 must also be restrained to
prevent over-resection that is known to hamper optimal HR and trigger global
genomic instability. However, mechanisms by which EXO1 is restrained are still
unclear. Here, we report that EXO1 is rapidly degraded by the ubiquitin
proteasome system soon after DSB induction in human cells. ATR inhibition
attenuated DNA-damage-induced EXO1 degradation, indicating that ATR-mediated
phosphorylation of EXO1 targets it for degradation. In accord with these results,
EXO1 became resistant to degradation when its SQ motifs required for ATR-mediated
phosphorylation were mutated. We show that upon the induction of DNA damage, EXO1
is ubiquitinated by a member of the Skp1-Cullin1-F-box (SCF) family of ubiquitin
ligases in a phosphorylation-dependent manner. Importantly, expression of
degradation-resistant EXO1 resulted in hyper-resection, which attenuated both
NHEJ and HR and severely compromised DSB repair resulting in chromosomal
instability. These findings indicate that the coupling of EXO1 activation with
its eventual degradation is a timing mechanism that limits the extent of DNA end
resection for accurate DNA repair.
PMID- 28515318
TI - Molecular mechanism of activation of class IA phosphoinositide 3-kinases (PI3Ks)
by membrane-localized HRas.
AB - Class IA PI3Ks are involved in the generation of the key lipid signaling molecule
phosphatidylinositol 3,4,5-trisphosphate (PIP3), and inappropriate activation of
this pathway is implicated in a multitude of human diseases, including cancer,
inflammation, and primary immunodeficiencies. Class IA PI3Ks are activated
downstream of the Ras superfamily of GTPases, and Ras-PI3K interaction plays a
key role in promoting tumor formation and maintenance in Ras-driven tumors.
Investigating the detailed molecular events in the Ras-PI3K interaction has been
challenging because it occurs on a membrane surface. Here, using maleimide
functionalized lipid vesicles, we successfully generated membrane-resident HRas
and evaluated its effect on PI3K signaling in lipid kinase assays and through
analysis with hydrogen-deuterium exchange MS. We screened all class IA PI3K
isoforms and found that HRas activates both p110alpha and p110delta isoforms but
does not activate p110beta. The p110alpha and p110delta activation by Ras was
synergistic with activation by a soluble phosphopeptide derived from receptor
tyrosine kinases. Hydrogen-deuterium exchange MS revealed that membrane-resident
HRas, but not soluble HRas, enhances conformational changes associated with
membrane binding by increasing membrane recruitment of both p110alpha and
p110delta. Together, these results afford detailed molecular insight into the Ras
PI3K signaling complex, provide a framework for screening Ras inhibitors, and
shed light on the isoform specificity of Ras-PI3K interactions in a native
membrane context.
PMID- 28515319
TI - The h-region of twin-arginine signal peptides supports productive binding of
bacterial Tat precursor proteins to the TatBC receptor complex.
AB - The twin-arginine translocation (Tat) pathway transports folded proteins across
bacterial membranes. Tat precursor proteins possess a conserved twin-arginine
(RR) motif in their signal peptides that is involved in their binding to the Tat
translocase, but some facets of this interaction remain unclear. Here, we
investigated the role of the hydrophobic (h-) region of the Escherichia coli
trimethylamine N-oxide reductase (TorA) signal peptide in TatBC receptor binding
in vivo and in vitro We show that besides the RR motif, a minimal, functional h
region in the signal peptide is required for Tat-dependent export in Escherichia
coli Furthermore, we identified mutations in the h-region that synergistically
suppressed the export defect of a TorA[KQ]-30aa-MalE Tat reporter protein in
which the RR motif was replaced with a lysine-glutamine pair. Strikingly, all
suppressor mutations increased the hydrophobicity of the h-region. By
systematically replacing a neutral residue in the h-region with various amino
acids, we detected a positive correlation between the hydrophobicity of the h
region and the translocation efficiency of the resulting reporter variants. In
vitro cross-linking of residues located in the periplasmically-oriented part of
the TatBC receptor to TorA[KQ]-30aa-MalE reporter variants harboring a more
hydrophobic h-region in their signal peptides confirmed that unlike in TorA[KQ]
30aa-MalE with an unaltered h-region, the mutated reporters moved deep into the
TatBC-binding cavity. Our results clearly indicate that, besides the Tat motif,
the h-region of the Tat signal peptides is another important binding determinant
that significantly contributes to the productive interaction of Tat precursor
proteins with the TatBC receptor complex.
PMID- 28515320
TI - Recognition of nectin-2 by the natural killer cell receptor T cell immunoglobulin
and ITIM domain (TIGIT).
AB - T cell immunoglobulin and ITIM domain (TIGIT) is an inhibitory receptor expressed
on the surface of natural killer (NK) cells. TIGIT recognizes nectin and nectin
like adhesion molecules and thus plays a critical role in the innate immune
response to malignant transformation. Although the TIGIT nectin-like protein-5
(necl-5) interaction is well understood, how TIGIT engages nectin-2, a receptor
that is broadly over-expressed in breast and ovarian cancer, remains unknown.
Here, we show that TIGIT bound to the immunoglobulin domain of nectin-2 that is
most distal from the membrane with an affinity of 6 MUm, which was moderately
lower than the affinity observed for the TIGIT/necl-5 interaction (3.2 MUm). The
TIGIT/nectin-2 binding disrupted pre-assembled nectin-2 oligomers, suggesting
that receptor-ligand and ligand-ligand associations are mutually exclusive
events. Indeed, the crystal structure of TIGIT bound to the first immunoglobulin
domain of nectin-2 indicated that the receptor and ligand dock using the same
molecular surface and a conserved "lock and key" binding motifs previously
observed to mediate nectin/nectin homotypic interactions as well as TIGIT/necl-5
recognition. Using a mutagenesis approach, we dissected the energetic basis for
the TIGIT/nectin-2 interaction and revealed that an "aromatic key" of nectin-2 is
critical for this interaction, whereas variations in the lock were tolerated.
Moreover, we found that the C-C' loop of the ligand dictates the TIGIT binding
hierarchy. Altogether, these findings broaden our understanding of nectin/nectin
receptor interactions and have implications for better understanding the
molecular basis for autoimmune disease and cancer.
PMID- 28515321
TI - Flavin-containing monooxygenases in aging and disease: Emerging roles for ancient
enzymes.
AB - Flavin-containing monooxygenases (FMOs) are primarily studied as xenobiotic
metabolizing enzymes with a prominent role in drug metabolism. In contrast,
endogenous functions and substrates of FMOs are less well understood. A growing
body of recent evidence, however, implicates FMOs in aging, several diseases, and
metabolic pathways. The evidence suggests an important role for these well
conserved proteins in multiple processes and raises questions about the
endogenous substrate(s) and regulation of FMOs. Here, we present an overview of
evidence for FMOs' involvement in aging and disease, discussing the biological
context and arguing for increased investigation into the function of these
enzymes.
PMID- 28515322
TI - Gbetagamma directly modulates vesicle fusion by competing with synaptotagmin for
binding to neuronal SNARE proteins embedded in membranes.
AB - Gi/o-coupled G protein-coupled receptors can inhibit neurotransmitter release at
synapses via multiple mechanisms. In addition to Gbetagamma-mediated modulation
of voltage-gated calcium channels (VGCC), inhibition can also be mediated through
the direct interaction of Gbetagamma subunits with the soluble N-ethylmaleimide
attachment protein receptor (SNARE) complex of the vesicle fusion apparatus.
Binding studies with soluble SNARE complexes have shown that Gbetagamma binds to
both ternary SNARE complexes, t-SNARE heterodimers, and monomeric SNAREs,
competing with synaptotagmin 1(syt1) for binding sites on t-SNARE. However, in
secretory cells, Gbetagamma, SNAREs, and synaptotagmin interact in the lipid
environment of a vesicle at the plasma membrane. To approximate this environment,
we show that fluorescently labeled Gbetagamma interacts specifically with lipid
embedded t-SNAREs consisting of full-length syntaxin 1 and SNAP-25B at the
membrane, as measured by fluorescence polarization. Fluorescently labeled syt1
undergoes competition with Gbetagamma for SNARE-binding sites in lipid
environments. Mutant Gbetagamma subunits that were previously shown to be more
efficacious at inhibiting Ca2+-triggered exocytotic release than wild-type
Gbetagamma were also shown to bind SNAREs at a higher affinity than wild type in
a lipid environment. These mutant Gbetagamma subunits were unable to inhibit VGCC
currents. Specific peptides corresponding to regions on Gbeta and Ggamma shown to
be important for the interaction disrupt the interaction in a concentration
dependent manner. In in vitro fusion assays using full-length t- and v-SNAREs
embedded in liposomes, Gbetagamma inhibited Ca2+/synaptotagmin-dependent fusion.
Together, these studies demonstrate the importance of these regions for the
Gbetagamma-SNARE interaction and show that the target of Gbetagamma, downstream
of VGCC, is the membrane-embedded SNARE complex.
PMID- 28515324
TI - The diferric-tyrosyl radical cluster of ribonucleotide reductase and cytosolic
iron-sulfur clusters have distinct and similar biogenesis requirements.
AB - How each metalloprotein assembles the correct metal at the proper binding site
presents challenges to the cell. The di-iron enzyme ribonucleotide reductase
(RNR) uses a diferric-tyrosyl radical (FeIII2-Y*) cofactor to initiate nucleotide
reduction. Assembly of this cofactor requires O2, FeII, and a reducing
equivalent. Recent studies show that RNR cofactor biosynthesis shares the same
source of iron, in the form of [2Fe-2S]-GSH2 from the monothiol glutaredoxin
Grx3/4, and the same electron source, in the form of the Dre2-Tah18 electron
transfer chain, with the cytosolic iron-sulfur protein assembly (CIA) machinery
required for maturation of [4Fe-4S] clusters in cytosolic and nuclear proteins.
Here, we further investigated the interplay between the formation of the FeIII2
Y* cofactor in RNR and the cellular iron-sulfur (Fe-S) protein biogenesis
pathways by examining both the iron loading into the RNR beta subunit and the RNR
catalytic activity in yeast mutants depleted of individual components of the
mitochondrial iron-sulfur cluster assembly (ISC) and the CIA machineries. We
found that both iron loading and cofactor assembly in RNR are dependent on the
ISC machinery. We also found that Dre2 is required for RNR cofactor formation but
appears to be dispensable for iron loading. None of the CIA components downstream
of Dre2 was required for RNR cofactor formation. Thus, the pathways for RNR and
Fe-S cluster biogenesis bifurcate after the Dre2-Tah18 step. We conclude that RNR
cofactor biogenesis requires the ISC machinery to mature the Grx3/4 and Dre2 Fe-S
proteins, which then function in iron and electron delivery to RNR, respectively.
PMID- 28515323
TI - beta-Adrenergic induction of lipolysis in hepatocytes is inhibited by ethanol
exposure.
AB - In liver steatosis (i.e. fatty liver), hepatocytes accumulate many large neutral
lipid storage organelles known as lipid droplets (LDs). LDs are important in the
maintenance of energy homeostasis, but the signaling mechanisms that stimulate LD
metabolism in hepatocytes are poorly defined. In adipocytes, catecholamines
target the beta-adrenergic (beta-AR)/cAMP pathway to activate cytosolic lipases
and induce their recruitment to the LD surface. Therefore, the goal of this study
was to determine whether hepatocytes, like adipocytes, also undergo cAMP-mediated
lipolysis in response to beta-AR stimulation. Using primary rat hepatocytes and
human hepatoma cells, we found that treatment with the beta-AR agent
isoproterenol caused substantial LD loss via activation of cytosolic lipases
adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL). beta
Adrenergic stimulation rapidly activated PKA, which led to the phosphorylation of
ATGL and HSL and their recruitment to the LD surface. To test whether this beta
AR-dependent lipolysis pathway was altered in a model of alcoholic fatty liver,
primary hepatocytes from rats fed a 6-week EtOH-containing Lieber-DeCarli diet
were treated with cAMP agonists. Compared with controls, EtOH-exposed hepatocytes
showed a drastic inhibition in beta-AR/cAMP-induced LD breakdown and the
phosphorylation of PKA substrates, including HSL. This observation was supported
in VA-13 cells, an EtOH-metabolizing human hepatoma cell line, which displayed
marked defects in both PKA activation and isoproterenol-induced ATGL
translocation to the LD periphery. In summary, these findings suggest that beta
AR stimulation mobilizes cytosolic lipases for LD breakdown in hepatocytes, and
perturbation of this pathway could be a major consequence of chronic EtOH insult
leading to fatty liver.
PMID- 28515325
TI - Mutual regulation between Polo-like kinase 3 and SIAH2 E3 ubiquitin ligase
defines a regulatory network that fine-tunes the cellular response to hypoxia and
nickel.
AB - Elevated cellular response to hypoxia, which contributes to cell transformation
and tumor progression, is a prominent feature of malignant cells in solid tumors.
Polo-like kinase 3 (Plk3) is a serine/threonine protein kinase known to inhibit
the cellular response to hypoxia and tumorigenesis. Nickel compounds are well
established human carcinogens that induce tumorigenesis partly through their
hypoxia-mimicking effects. Despite previous research efforts, the role of Plk3 in
the hypoxic response induced by hypoxia or nickel is not completely understood.
Here, we show that NiCl2 (Ni(II)) or hypoxia reduces the protein level and
shortens the half-life of cytoplasmic Plk3 in a ubiquitin-proteasome-dependent
manner. We identify SIAH2, a RING finger E3 ubiquitin ligase associated with the
cellular hypoxic response, to be the ubiquitin E3 ligase that mediates the
degradation of Plk3. We show that SIAH2 binds to Plk3 and mediates its
ubiquitination primarily through its polo-box domain. We report that USP28, a
deubiquitinase known to be inhibitable by Ni(II) or hypoxia, may also contribute
to the suppression of the Plk3 protein by Ni(II). We also show that Plk3 in turn
suppresses the SIAH2 protein level in a kinase activity-dependent manner. Our
study revealed an interesting mutual regulation between Plk3 and SIAH2 and
uncovered a regulatory network that functions to fine-tune the cellular hypoxic
response. We propose that suppression of Plk3 expression contributes to
carcinogenesis and tumor progression induced by nickel compounds.
PMID- 28515326
TI - Semantic closure demonstrated by the evolution of a universal constructor
architecture in an artificial chemistry.
AB - We present a novel stringmol-based artificial chemistry system modelled on the
universal constructor architecture (UCA) first explored by von Neumann. In a UCA,
machines interact with an abstract description of themselves to replicate by
copying the abstract description and constructing the machines that the abstract
description encodes. DNA-based replication follows this architecture, with DNA
being the abstract description, the polymerase being the copier, and the ribosome
being the principal machine in expressing what is encoded on the DNA. This
architecture is semantically closed as the machine that defines what the abstract
description means is itself encoded on that abstract description. We present a
series of experiments with the stringmol UCA that show the evolution of the
meaning of genomic material, allowing the concept of semantic closure and
transitions between semantically closed states to be elucidated in the light of
concrete examples. We present results where, for the first time in an in silico
system, simultaneous evolution of the genomic material, copier and constructor of
a UCA, giving rise to viable offspring.
PMID- 28515327
TI - Minimum action principle and shape dynamics.
AB - In this paper, we propose a new method for computing a distance between two
shapes embedded in three-dimensional space. Instead of comparing directly the
geometric properties of the two shapes, we measure the cost of deforming one of
the two shapes into the other. The deformation is computed as the geodesic
between the two shapes in the space of shapes. The geodesic is found as a
minimizer of the Onsager-Machlup action, based on an elastic energy for shapes
that we define. Its length is set to be the integral of the action along that
path; it defines an intrinsic quasi-metric on the space of shapes. We illustrate
applications of our method to geometric morphometrics using three datasets
representing bones and teeth of primates. Experiments on these datasets show that
the variational quasi-metric we have introduced performs remarkably well both in
shape recognition and in identifying evolutionary patterns, with success rates
similar to, and in some cases better than, those obtained by expert observers.
PMID- 28515329
TI - Inference of facultative mobility in the enigmatic Ediacaran organism
Parvancorina.
AB - Establishing how Ediacaran organisms moved and fed is critical to deciphering
their ecological and evolutionary significance, but has long been confounded by
their non-analogue body plans. Here, we use computational fluid dynamics to
quantitatively analyse water flow around the Ediacaran taxon Parvancorina,
thereby testing between competing models for feeding mode and mobility. The
results show that flow was not distributed evenly across the organism, but was
directed towards localized areas; this allows us to reject osmotrophy, and
instead supports either suspension feeding or detritivory. Moreover, the patterns
of recirculating flow differ substantially with orientation to the current,
suggesting that if Parvancorina was a suspension feeder, it would have been most
efficient if it was able to re-orient itself with respect to current direction,
and thus ensure flow was directed towards feeding structures. Our simulations
also demonstrate that the amount of drag varied with orientation, indicating that
Parvancorina would have greatly benefited from adjusting its position to minimize
drag. Inference of facultative mobility in Parvancorina suggests that Ediacaran
benthic ecosystems might have possessed a higher proportion of mobile taxa than
currently appreciated from trace fossil studies. Furthermore, this inference of
movement suggests the presence of musculature or appendages that are not
preserved in fossils, but which would noneltheless support a bilaterian affinity
for Parvancorina.
PMID- 28515328
TI - Mechanotransmission in endothelial cells subjected to oscillatory and multi
directional shear flow.
AB - Local haemodynamics are linked to the non-uniform distribution of atherosclerosic
lesions in arteries. Low and oscillatory (reversing in the axial flow direction)
wall shear stress (WSS) induce inflammatory responses in endothelial cells (ECs)
mediating disease localization. The objective of this study is to investigate
computationally how the flow direction (reflected in WSS variation on the EC
surface over time) influences the forces experienced by structural components of
ECs that are believed to play important roles in mechanotransduction. A three
dimensional, multi-scale, multi-component, viscoelastic model of focally adhered
ECs is developed, in which oscillatory WSS (reversing or non-reversing) parallel
to the principal flow direction, or multi-directional oscillatory WSS with
reversing axial and transverse components are applied over the EC surface. The
computational model includes the glycocalyx layer, actin cortical layer, nucleus,
cytoskeleton, focal adhesions (FAs), stress fibres and adherens junctions (ADJs).
We show the distinct effects of atherogenic flow profiles (reversing
unidirectional flow and reversing multi-directional flow) on subcellular
structures relative to non-atherogenic flow (non-reversing flow). Reversing flow
lowers stresses and strains due to viscoelastic effects, and multi-directional
flow alters stress on the ADJs perpendicular to the axial flow direction. The
simulations predict forces on integrins, ADJ filaments and other substructures in
the range that activate mechanotransduction.
PMID- 28515331
TI - Cannibalism by damselflies increases with rising temperature.
AB - Trophic interactions are likely to change under climate warming. These
interactions can be altered directly by changing consumption rates, or indirectly
by altering growth rates and size asymmetries among individuals that in turn
affect feeding. Understanding these processes is particularly important for
intraspecific interactions, as direct and indirect changes may exacerbate
antagonistic interactions. We examined the effect of temperature on activity
rate, growth and intraspecific size asymmetries, and how these temperature
dependencies affected cannibalism in Lestes congener, a damselfly with marked
intraspecific variation in size. Temperature increased activity rates and
exacerbated differences in body size by increasing growth rates. Increased
activity and changes in body size interacted to increase cannibalism at higher
temperatures. We argue that our results are likely to be general to species with
life-history stages that vary in their temperature dependencies, and that the
effects of climate change on communities may depend on the temperature
dependencies of intraspecific interactions.
PMID- 28515330
TI - Post-fire recovery of torpor and activity patterns of a small mammal.
AB - To cope with the post-fire challenges of decreased availability of food and
shelter, brown antechinus (Antechinus stuartii), a small marsupial mammal,
increase the use of energy-conserving torpor and reduce activity. However, it is
not known how long it takes for animals to resume pre-fire torpor and activity
patterns during the recovery of burnt habitat. Therefore, we tested the
hypothesis that antechinus will adjust torpor use and activity after a fire
depending on vegetation recovery. We simultaneously quantified torpor and
activity patterns for female antechinus from three adjacent areas: (i) the area
of a management burn 1 year post-fire, (ii) an area that was burned 2 years
prior, and (iii) a control area. In comparison to shortly after the management
burn, antechinus in all three groups displayed less frequent and less pronounced
torpor while being more active. We provide the first evidence that only 1 year
post-fire antechinus resume pre-fire torpor and activity patterns, probably in
response to the return of herbaceous ground cover and foraging opportunities.
PMID- 28515332
TI - The unusual tracheal system within the wing membrane of a dragonfly.
AB - Some consider that the first winged insects had living tissue inside the wing
membrane, resembling larval gills or developing wing pads. However, throughout
the developmental process of the wing membrane of modern insects, cells and
tracheoles in the lumen between dorsal and ventral cuticle disappear and both
cuticles become fused. This process results in the rather thin rigid stable
structure of the membrane. The herewith described remarkable case of the
dragonfly Zenithoptera lanei shows that in some highly specialized wings, the
membrane can still be supplemented by tracheae. Such a characteristic of the wing
membrane presumably represents a strong specialization for the synthesis of
melanin-filled nanolayers of the cuticle, nanospheres inside the wing membrane
and complex arrangement of wax crystals on the membrane surface, all responsible
for unique structural coloration.
PMID- 28515333
TI - Effective cybersecurity is fundamental to patient safety.
PMID- 28515334
TI - Central-acting therapeutics alleviate respiratory weakness caused by heart
failure-induced ventilatory overdrive.
AB - Diaphragmatic weakness is a feature of heart failure (HF) associated with dyspnea
and exertional fatigue. Most studies have focused on advanced stages of HF,
leaving the cause unresolved. The long-standing theory is that pulmonary edema
imposes a mechanical stress, resulting in diaphragmatic remodeling, but stable HF
patients rarely exhibit pulmonary edema. We investigated how diaphragmatic
weakness develops in two mouse models of pressure overload-induced HF. As in HF
patients, both models had increased eupneic respiratory pressures and ventilatory
drive. Despite the absence of pulmonary edema, diaphragmatic strength
progressively declined during pressure overload; this decline correlated with a
reduction in diaphragm cross-sectional area and preceded evidence of muscle
weakness. We uncovered a functional codependence between angiotensin II and beta
adrenergic (beta-ADR) signaling, which increased ventilatory drive. Chronic
overdrive was associated with increased PERK (double-stranded RNA-activated
protein kinase R-like ER kinase) expression and phosphorylation of EIF2alpha
(eukaryotic translation initiation factor 2alpha), which inhibits protein
synthesis. Inhibition of beta-ADR signaling after application of pressure
overload normalized diaphragm strength, Perk expression, EIF2alpha
phosphorylation, and diaphragmatic cross-sectional area. Only drugs that were
able to penetrate the blood-brain barrier were effective in treating ventilatory
overdrive and preventing diaphragmatic atrophy. These data provide insight into
why similar drugs have different benefits on mortality and symptomatology,
despite comparable cardiovascular effects.
PMID- 28515337
TI - Hung over? Maybe it's your overactive microglia.
AB - Acute ethanol intake is associated with a mild suppression of microglial activity
followed by a more robust inflammatory reaction during the withdrawal period.
PMID- 28515335
TI - In situ bone tissue engineering via ultrasound-mediated gene delivery to
endogenous progenitor cells in mini-pigs.
AB - More than 2 million bone-grafting procedures are performed each year using
autografts or allografts. However, both options carry disadvantages, and there
remains a clear medical need for the development of new therapies for massive
bone loss and fracture nonunions. We hypothesized that localized ultrasound
mediated, microbubble-enhanced therapeutic gene delivery to endogenous stem cells
would induce efficient bone regeneration and fracture repair. To test this
hypothesis, we surgically created a critical-sized bone fracture in the tibiae of
Yucatan mini-pigs, a clinically relevant large animal model. A collagen scaffold
was implanted in the fracture to facilitate recruitment of endogenous mesenchymal
stem/progenitor cells (MSCs) into the fracture site. Two weeks later,
transcutaneous ultrasound-mediated reporter gene delivery successfully
transfected 40% of cells at the fracture site, and flow cytometry showed that 80%
of the transfected cells expressed MSC markers. Human bone morphogenetic protein
6 (BMP-6) plasmid DNA was delivered using ultrasound in the same animal model,
leading to transient expression and secretion of BMP-6 localized to the fracture
area. Micro-computed tomography and biomechanical analyses showed that ultrasound
mediated BMP-6 gene delivery led to complete radiographic and functional fracture
healing in all animals 6 weeks after treatment, whereas nonunion was evident in
control animals. Collectively, these findings demonstrate that ultrasound
mediated gene delivery to endogenous mesenchymal progenitor cells can effectively
treat nonhealing bone fractures in large animals, thereby addressing a major
orthopedic unmet need and offering new possibilities for clinical translation.
PMID- 28515338
TI - An "eye" for rhythm.
AB - A new analytical method allows reconstruction of circadian gene expression in
human biopsy samples.
PMID- 28515336
TI - The effects of micronutrient deficiencies on bacterial species from the human gut
microbiota.
AB - Vitamin and mineral (micronutrient) deficiencies afflict 2 billion people.
Although the impact of these imbalances on host biology has been studied
extensively, much less is known about their effects on the gut microbiota of
developing or adult humans. Therefore, we established a community of cultured,
sequenced human gut-derived bacterial species in gnotobiotic mice and fed the
animals a defined micronutrient-sufficient diet, followed by a derivative diet
devoid of vitamin A, folate, iron, or zinc, followed by return to the sufficient
diet. Acute vitamin A deficiency had the largest effect on bacterial community
structure and metatranscriptome, with Bacteroides vulgatus, a prominent
responder, increasing its abundance in the absence of vitamin A. Applying retinol
selection to a library of 30,300 B. vulgatus transposon mutants revealed that
disruption of acrR abrogated retinol sensitivity. Genetic complementation
studies, microbial RNA sequencing, and transcription factor-binding assays
disclosed that AcrR is a repressor of an adjacent AcrAB-TolC efflux system.
Retinol efflux measurements in wild-type and acrR-mutant strains plus treatment
with a pharmacologic inhibitor of the efflux system revealed that AcrAB-TolC is a
determinant of retinol and bile acid sensitivity in B. vulgatus Acute vitamin A
deficiency was associated with altered bile acid metabolism in vivo, raising the
possibility that retinol, bile acid metabolites, and AcrAB-TolC interact to
influence the fitness of B. vulgatus and perhaps other microbiota members. This
type of preclinical model can help to develop mechanistic insights about the
effects of, and more effective treatment strategies for micronutrient
deficiencies.
PMID- 28515339
TI - Chemotherapy-treated cells go up in flames.
AB - Apoptosis induced by chemotherapies can also trigger proinflammatory pyroptosis.
PMID- 28515340
TI - Turning back the clock.
AB - Increased DNA breaks in aging skeletal muscle activate the DNA-PK pathway,
whereas blocking this pathway improves mitochondrial density, physical fitness,
body weight, and insulin resistance in mice.
PMID- 28515342
TI - Clinical presentations and epidemiology of vascular dementia.
AB - Cerebrovascular and cardiovascular diseases cause vascular brain injury that can
lead to vascular cognitive impairment (VCI). VCI is the second most common
neuropathology of dementia and mild cognitive impairment (MCI), accounting for up
to one-third of the population risk. It is frequently present along with other
age-related pathologies such as Alzheimer's disease (AD). Multiple etiology
dementia with both VCI and AD is the single most common cause of later life
dementia. There are two main clinical syndromes of VCI: post-stroke VCI in which
cognitive impairment is the immediate consequence of a recent stroke and VCI
without recent stroke in which cognitive impairment is the result of covert
vascular brain injury detected only on neuroimaging or neuropathology. VCI is a
syndrome that can result from any cause of infarction, hemorrhage, large artery
disease, cardioembolism, small vessel disease, or other cerebrovascular or
cardiovascular diseases. Secondary prevention of further vascular brain injury
may improve outcomes in VCI.
PMID- 28515343
TI - Kidney, heart and brain: three organs targeted by ageing and glycation.
AB - Advanced glycation end-product (AGE) is the generic term for a heterogeneous
group of derivatives arising from a non-enzymatic reaction between reducing
sugars and proteins. In recent years, evidence has accumulated that incriminates
AGEs in pathogenic processes associated with both chronic hyperglycaemia and age
related diseases. Regardless of their exogenous or endogenous origin, the
accumulation of AGEs and their derivatives could promote accelerated ageing by
leading to protein modifications and activating several inflammatory signalling
pathways via AGE-specific receptors. However, it remains to be demonstrated
whether preventing the accumulation of AGEs and their effects is an important
therapeutic option for successful ageing. The present review gives an overview of
the current knowledge on the pathogenic role of AGEs by focusing on three AGE
target organs: kidney, heart and brain. For each of these organs we concentrate
on an age-related disease, each of which is a major public health issue: chronic
kidney disease, heart dysfunction and neurodegenerative diseases. Even though
strong connections have been highlighted between glycation and age-related
pathogenesis, causal links still need to be validated. In each case, we report
evidence and uncertainties suggested by animal or epidemiological studies on the
possible link between pathogenesis and glycation in a chronic hyperglycaemic
state, in the absence of diabetes, and with exogenous AGEs alone. Finally, we
present some promising anti-AGE strategies that are currently being studied.
PMID- 28515341
TI - BET bromodomain inhibition suppresses innate inflammatory and profibrotic
transcriptional networks in heart failure.
AB - Despite current standard of care, the average 5-year mortality after an initial
diagnosis of heart failure (HF) is about 40%, reflecting an urgent need for new
therapeutic approaches. Previous studies demonstrated that the epigenetic reader
protein bromodomain-containing protein 4 (BRD4), an emerging therapeutic target
in cancer, functions as a critical coactivator of pathologic gene transactivation
during cardiomyocyte hypertrophy. However, the therapeutic relevance of these
findings to human disease remained unknown. We demonstrate that treatment with
the BET bromodomain inhibitor JQ1 has therapeutic effects during severe,
preestablished HF from prolonged pressure overload, as well as after a massive
anterior myocardial infarction in mice. Furthermore, JQ1 potently blocks agonist
induced hypertrophy in human induced pluripotent stem cell-derived cardiomyocytes
(iPSC-CMs). Integrated transcriptomic analyses across animal models and human
iPSC-CMs reveal that BET inhibition preferentially blocks transactivation of a
common pathologic gene regulatory program that is robustly enriched for NFkappaB
and TGF-beta signaling networks, typified by innate inflammatory and profibrotic
myocardial genes. As predicted by these specific transcriptional mechanisms, we
found that JQ1 does not suppress physiological cardiac hypertrophy in a mouse
swimming model. These findings establish that pharmacologically targeting innate
inflammatory and profibrotic myocardial signaling networks at the level of
chromatin is effective in animal models and human cardiomyocytes, providing the
critical rationale for further development of BET inhibitors and other epigenomic
medicines for HF.
PMID- 28515344
TI - Kidney-brain axis inflammatory cross-talk: from bench to bedside.
AB - Epidemiologic data suggest that individuals at all stages of chronic kidney
disease (CKD) have a higher risk of developing neuropsychiatric disorders,
cognitive impairment, and dementia. This risk is generally explained by the high
prevalence of both symptomatic and subclinical ischemic cerebrovascular lesions.
However, other potential mechanisms, including cytokine/chemokine release,
production of reactive oxygen species (ROS), circulating and local formation of
trophic factors and of renin-angiotensin system (RAS) molecules, could also be
involved, especially in the absence of obvious cerebrovascular disease. In this
review, we discuss experimental and clinical evidence for the role of these
mechanisms in kidney-brain cross-talk. In addition, we hypothesize potential
pathways for the interactions between kidney and brain and their
pathophysiological role in neuropsychiatric and cognitive changes found in
patients with CKD. Understanding the pathophysiologic interactions between renal
impairment and brain function is important in order to minimize the risk for
future cognitive impairment and to develop new strategies for innovative
pharmacological treatment.
PMID- 28515345
TI - Genetic factors associated with risk of metabolic syndrome and hepatocellular
carcinoma.
AB - Although the metabolic syndrome is a commonplace topic, its potential threats to
public health is a problem that cannot be neglected. As the living conditions
improved significantly over the past few years, the morbidity of metabolic
syndrome has also steadily risen, and the onset age is becoming younger. The
hepatocellular carcinoma (HCC), is one of the most prevalent life-threatening
human cancers worldwide, incidence of which is also on the rise, gradually
occupied the top of the list associated with metabolic syndrome related
complication. Despite the advanced improvement of HCC management, the lifestyle,
environmental factors, obesity, hepatitis B virus (HBV) infection have been
recognized as risk factors for the development of liver cancer. In recent years,
genetic studies, especially the genome-wide association studies (GWASs) were
widely performed, a new era of the human genome research was created, which has
significantly promoted the study of complex disease genetics. These progresses
have contributed to the discovery of abundant number of genomic loci convincingly
linked with complex metabolic feature and HCC. In this review, we briefly
summarize the association between metabolic syndrome and HCC, focusing on the
genetic factors contributed to metabolic syndrome and HCC.
PMID- 28515348
TI - Relation of phosphodiesterase type 5 inhibitors and malignant melanoma: a meta
analysis and systematic review.
AB - Data on the association between using PDE5 inhibitors and malignant melanoma are
conflicting. To estimate the relation of using PDE5 inhibitors with risk of
malignant melanoma, Medline (Ovid) and Embase (Ovid) databases were searched up
to February 2017, and a random effects model was used to calculate the summary
risk estimates. Five observational studies were included. Five studies reports
encompassed a total of 15,979 melanoma cases occurring among 1, 188,414
participants. The pooled multivariable-adjusted RR of melanoma in patients with
using PDE5 inhibitors was 1.12 (95% CI: 1.03-1.21, I2 = 0.48). Findings from this
systematic review support that PDE5 inhibitor use is associated with increased
risk of melanoma in ED patients, the result remains inclusive and warrants
further study in the future.
PMID- 28515346
TI - The novel complex combination of alum, CpG ODN and HH2 as adjuvant in cancer
vaccine effectively suppresses tumor growth in vivo.
AB - Single-component adjuvant is prone to eliciting a specific type of Th1 or Th2
response. So, the development of combinatorial adjuvants inducing a robust mixed
Th1/Th2 response is a promising vaccination strategy against cancer. Here, we
describe a novel combination of aluminum salts (alum), CpG oligodeoxynucleotide
(CpG) and innate defense regulator peptide HH2 for improving anti-tumor immune
responses. The CpG-HH2 complex significantly enhanced the production of IFN
gamma, TNF-alpha and IL-1beta, promoted the uptake of antigen and strengthened
the activation of p38, Erk1/2 and NF-kappaB in vitro, compared to CpG or HH2
alone. Immunization with NY-ESO-1 antigen plus alum-CpG-HH2 combinatorial
adjuvant effectively inhibited tumor growth and reduced tumor burden in
prophylactic and therapeutic tumor models and even in passive serum or cellular
therapy. In addition, co-administration of NY-ESO-1 with alum-CpG-HH2
combinatorial adjuvant markedly activated NK cell cytotoxicity, induced antibody
dependent cellular cytotoxicity (ADCC), dramatically elicited cytotoxic T
lymphocytes (CTLs) response, and increased infiltrating lymphocytes in tumors.
Moreover, in vivo depletion of CD8+ T cells completely and depletion of NK cells
partially blocked the anti-tumor activity of NY-ESO-1-alum-CpG-HH2 immunization.
Overall, our results demonstrate a novel adjuvant combination for cancer vaccine
with efficient immunomodulation by stimulating innate immunity and mediating
adaptive immunity.
PMID- 28515349
TI - APC hypermethylation for early diagnosis of colorectal cancer: a meta-analysis
and literature review.
AB - Adenomatous polyposis coli (APC) promoter hypermethylation has been frequently
observed in colorectal cancer (CRC). The association between APC promoter
methylation and clinicopathological significance in CRC is under investigation.
We performed a meta-analysis to quantitatively evaluate the significance of APC
methylation in CRC. The study included a total of 24 articles and 2025 CRC
patients. The frequency of APC promoter hypermethylation was significantly higher
in colorectal adenoma than in normal colorectal tissue, OR was 5.76, 95% CI, 2.45
13.56; p<0.0001, I2=0%. APC promoter more frequently hypermethylated in CRC stage
I compared to normal colorectal tissue, OR was 13.42, 95% CI, 3.66-49.20;
p<0.0001, I2=31%. The risk of incidence of CRC was significantly correlated to
APC promoter hypermethylation, pooled OR was 9.80, 95%CI, 6.07-15.81; p<0.00001,
I2=43%. APC methylation was not associated with grade, stage of CRC as well as
tumor location, patients' gender, and smoking behavior. The results indicate that
APC promoter hypermethylation is an early event in carcinogenesis of CRC, could
be a valuable diagnostic marker for early-stage CRC. APC methylation is not
significantly associated with overall survival in patients with CRC. APC is a
potential drug target for development of personalized treatment.
PMID- 28515350
TI - FAM3A enhances adipogenesis of 3T3-L1 preadipocytes via activation of ATP-P2
receptor-Akt signaling pathway.
AB - FAM3A plays important roles in regulating hepatic glucose/lipid metabolism and
the proliferation of VSMCs. This study determined the role and mechanism of FAM3A
in the adipogenesis of 3T3-L1 preadipocytes. During the adipogenesis of 3T3-L1
preadipocytes, FAM3A expression was significantly increased. FAM3A overexpression
enhanced 3T3-L1 preadipocyte adipogenesis with increased phosphorylated Akt
(pAkt) level, whereas FAM3A silencing inhibited 3T3-L1 preadipocyte adipogenesis
with reduced pAkt level. Moreover, FAM3A silencing reduced the expression and
secretion of adipokines in 3T3-L1 cells. FAM3A protein is mainly located in
mitochondrial fraction of 3T3-L1 cells and mouse adipose tissue. FAM3A
overexpression increased, whereas FAM3A silencing decreased ATP production in 3T3
L1 preadipocytes. FAM3A-induced adipogenesis of 3T3-L1 preadipocytes was blunted
by inhibitor of P2 receptor. In white adipose tissues of db/db and HFD-fed obese
mice, FAM3A expression was reduced. One-month rosiglitazone administration
upregulated FAM3A expression, and increased cellular ATP content and pAkt level
in white adipose tissues of normal and obese mice. In conclusion, FAM3A enhances
the adipogenesis of preadipocytes by activating ATP-P2 receptor-Akt pathway.
Under obese condition, a decrease in FAM3A expression in adipose tissues plays
important roles in the development of adipose dysfunction and type 2 diabetes.
PMID- 28515351
TI - Local immune response depends on p16INK4a status of primary tumor in vulvar
squamous cell carcinoma.
AB - BACKGROUND: The p16Ink4a is not a surrogate marker for high-risk human papilloma
virus (HPV) genotypes but indicates better prognosis in vulvar squamous cell
carcinoma patients. Our recent study confirmed substantial mismatch between
p16Ink4a and high-risk HPV-status as well as revealed that p16Ink4a
overexpression itself is an independent prognostic factor for vulvar cancer. AIM:
To determine significance of the tumor infiltrating immune cells and p16Ink4a
status for better outcome of patients with vulvar cancer. METHODS:
Intraepithelial tumor infiltrating lymphocytes: CD8+, CD4+, FOXP3+, CD56+, tumor
associated macrophages: CD68+, and GZB+ cells were calculated in 85 vulvar
squamous cell carcinomas with previously defined p16Ink4a and high-risk HPV
status. Number of intraepithelial CD8+, CD4+, FOXP3+, CD56+, CD68+ and GZB+ cells
were compared between tumors with different p16INK4a status and overlapping high
risk HPV-status separately. Survival analyses included the Kaplan-Meier method,
log-rank test and Cox proportional hazards model. RESULTS: p16Ink4a-negative
tumors were more infiltrated by intraepithelial CD8+, CD4+ and GZB+ cells than
p16Ink4a-positive tumors (p=0.032, p=0.016 and p=0.007 respectively). High-risk
HPV-status did not correlate with the infiltration of immune cells. Median follow
up was 89.20 months (range 1.7-189.5). High CD4+ and CD56+ indices were
correlated with prognosis in p16Ink4a-positive cases (p=0.039 and p=0.013
respectively). Low CD68+ infiltrates were correlated with prognosis in p16Ink4a
negative cases (p=0.018). CONCLUSION: p16Ink4a-status impacts local immune
surveillance as represented by tumor infiltrating immune cells. Immunologic
effects contributing to clinical outcome might depend on p16Ink4a-overexpression.
PMID- 28515352
TI - Intensity-modulated radiotherapy provides better quality of life than two
dimensional conventional radiotherapy for patients with stage II nasopharyngeal
carcinoma.
AB - Two-dimensional conventional radiotherapy (2D-CRT) and intensity-modulated
radiotherapy (IMRT) are effective for control of nasopharyngeal carcinoma (NPC).
The purpose of this study was to compare the quality of life (QoL) of stage II
NPC patients treated with 2D-CRT versus IMRT. We conducted a cross-sectional
study of 106 patients with stage II NPC treated with 2D-CRT (n = 47) versus IMRT
(n = 59) between June 2008 and June 2013. For all subjects, disease-free survival
was more than 3 years. QoL was assessed using the European Organization for
Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ
C30) questions and the Head and Neck 35 (EORTC QLQ-H&N35) questions. Patients
receiving IMRT with or without concurrent chemotherapy had better outcomes in
head and neck related symptoms and general aspects of QoL than those receiving 2D
CRT with or without concurrent chemotherapy. Thus, IMRT improves the QoL of
patients with stage II NPC as compared to 2D-CRT.
PMID- 28515355
TI - Translational reprogramming of colorectal cancer cells induced by 5-fluorouracil
through a miRNA-dependent mechanism.
AB - 5-Fluorouracil (5-FU) is a widely used chemotherapeutic drug in colorectal
cancer. Previous studies showed that 5-FU modulates RNA metabolism and mRNA
expression. In addition, it has been reported that 5-FU incorporates into the
RNAs constituting the translational machinery and that 5-FU affects the amount of
some mRNAs associated with ribosomes. However, the impact of 5-FU on
translational regulation remains unclear. Using translatome profiling, we report
that a clinically relevant dose of 5-FU induces a translational reprogramming in
colorectal cancer cell lines. Comparison of mRNA distribution between polysomal
and non-polysomal fractions in response to 5-FU treatment using microarray
quantification identified 313 genes whose translation was selectively regulated.
These regulations were mostly stimulatory (91%). Among these genes, we showed
that 5-FU increases the mRNA translation of HIVEP2, which encodes a transcription
factor whose translation in normal condition is known to be inhibited by mir-155.
In response to 5-FU, the expression of mir-155 decreases thus stimulating the
translation of HIVEP2 mRNA. Interestingly, the 5-FU-induced increase in specific
mRNA translation was associated with reduction of global protein synthesis.
Altogether, these findings indicate that 5-FU promotes a translational
reprogramming leading to the increased translation of a subset of mRNAs that
involves at least for some of them, miRNA-dependent mechanisms. This study
supports a still poorly evaluated role of translational control in drug response.
PMID- 28515357
TI - E2F1 inhibits circulating cholesterol clearance by regulating Pcsk9 expression in
the liver.
AB - Cholesterol accumulation in the liver is an early event in nonalcoholic fatty
liver disease (NAFLD). Here, we demonstrate that E2F1 plays a crucial role in
maintaining cellular cholesterol homeostasis by regulating cholesterol uptake via
proprotein convertase subtilisin/kexin 9 (PCSK9), an enzyme that promotes low
density lipoprotein receptor (LDLR) degradation upon activation. E2f1-/- mice
display reduced total plasma cholesterol levels and increased cholesterol content
in the liver. In this study, we show that E2f1 deletion in cellular and mouse
models leads to a marked decrease in Pcsk9 expression and an increase in LDLR
expression. In addition to the upregulation of LDLR, we report that E2f1-/-
hepatocytes exhibit increased LDL uptake. ChIP-Seq and PCSK9 promoter reporter
experiments confirmed that E2F1 binds to and transactivates the PCSK9 promoter.
Interestingly, E2f1-/- mice fed a high-cholesterol diet (HCD) display a fatty
liver phenotype and liver fibrosis, which is reversed by reexpression of PCSK9 in
the liver. Collectively, these data indicate that E2F1 regulates cholesterol
uptake and that the loss of E2F1 leads to abnormal cholesterol accumulation in
the liver and the development of fibrosis in response to an HCD.
PMID- 28515356
TI - Licensing delineates helper and effector NK cell subsets during viral infection.
AB - Natural killer (NK) cells can be divided into phenotypic subsets based on
expression of receptors that bind self-MHC-I molecules, a concept termed
licensing or education. Here we show NK cell subsets with different migratory,
effector, and immunoregulatory functions in dendritic cell and antigen (ag)
specific CD8+ T cell responses during influenza and murine cytomegalovirus
infections. Shortly after infection, unlicensed NK cells localized in draining
lymph nodes and produced GM-CSF, which correlated with the expansion and
activation of dendritic cells, and resulted in greater and sustained ag-specific
T cell responses. In contrast, licensed NK cells preferentially migrated to
infected tissues and produced IFN-gamma. Importantly, human NK cell subsets
exhibited similar phenotypic characteristics. Collectively, our studies
demonstrate a critical demarcation between the functions of licensed and
unlicensed NK cell subsets, with the former functioning as the classical effector
subset and the latter as the stimulator of adaptive immunity helping to prime
immune responses.
PMID- 28515359
TI - T cell progenitor therapy-facilitated thymopoiesis depends upon thymic input and
continued thymic microenvironment interaction.
AB - Infusion of in vitro-derived T cell progenitor (proT) therapy with hematopoietic
stem cell transplant aids the recovery of the thymus damaged by total body
irradiation. To understand the interaction between proTs and the thymic
microenvironment, WT mice were lethally irradiated and given T cell-deficient
(Rag1-/-) marrow with WT in vitro-generated proTs, limiting mature T cell
development to infused proTs. ProTs within the host thymus led to a significant
increase in thymic epithelial cells (TECs) by day 21 after transplant, increasing
actively cycling TECs. Upon thymus egress (day 28), proT TEC effects were lost,
suggesting that continued signaling from proTs is required to sustain TEC cycling
and cellularity. Thymocytes increased significantly by day 21, followed by a
significant improvement in mature T cell numbers in the periphery by day 35. This
protective surge was temporary, receding by day 60. Double-negative 2 (DN2) proTs
selectively increased thymocyte number, while DN3 proTs preferentially increased
TECs and T cells in the spleen that persisted at day 60. These findings highlight
the importance of the interaction between proTs and TECs in the proliferation and
survival of TECs and that the maturation stage of proTs has unique effects on
thymopoiesis and peripheral T cell recovery.
PMID- 28515358
TI - IRF5 distinguishes severe asthma in humans and drives Th1 phenotype and airway
hyperreactivity in mice.
AB - Severe asthma (SA) is a significant problem both clinically and economically,
given its poor response to corticosteroids (CS). We recently reported a complex
type 1-dominated (IFN-gamma-dominated) immune response in more than 50% of severe
asthmatics despite high-dose CS treatment. Also, IFN-gamma was found to be
critical for increased airway hyperreactivity (AHR) in our model of SA. The
transcription factor IRF5 expressed in M1 macrophages can induce a Th1/Th17
response in cocultured human T cells. Here we show markedly higher expression of
IRF5 in bronchoalveolar lavage (BAL) cells of severe asthmatics as compared with
that in cells from milder asthmatics or healthy controls. Using our SA mouse
model, we demonstrate that lack of IRF5 in lymph node migratory DCs severely
limits their ability to stimulate the generation of IFN-gamma- and IL-17
producing CD4+ T cells and IRF5-/- mice subjected to the SA model displayed
significantly lower IFN-gamma and IL-17 responses, albeit showing a reciprocal
increase in Th2 response. However, the absence of IRF5 rendered the mice
responsive to CS with suppression of the heightened Th2 response. These data
support the notion that IRF5 inhibition in combination with CS may be a viable
approach to manage disease in a subset of severe asthmatics.
PMID- 28515360
TI - A human PSMB11 variant affects thymoproteasome processing and CD8+ T cell
production.
AB - The Psmb11-encoded beta5t subunit of the thymoproteasome, which is specifically
expressed in cortical thymic epithelial cells (cTECs), is essential for the
optimal positive selection of functionally competent CD8+ T cells in mice. Here,
we report that a human genomic PSMB11 variation, which is detectable at an
appreciable allele frequency in human populations, alters the beta5t amino acid
sequence that affects the processing of catalytically active beta5t proteins. The
introduction of this variation in the mouse genome revealed that the
heterozygotes showed reduced beta5t expression in cTECs and the homozygotes
further exhibited reduction in the cellularity of CD8+ T cells. No severe health
problems were noticed in many heterozygous and 5 homozygous human individuals.
Long-term analysis of health status, particularly in the homozygotes, is expected
to improve our understanding of the role of the thymoproteasome-dependent
positive selection of CD8+ T cells in humans.
PMID- 28515361
TI - Lupus and proliferative nephritis are PAD4 independent in murine models.
AB - Though recent reports suggest that neutrophil extracellular traps (NETs) are a
source of antigenic nucleic acids in systemic lupus erythematosus (SLE), we
recently showed that inhibition of NETs by targeting the NADPH oxidase complex
via cytochrome b-245, beta polypeptide (cybb) deletion exacerbated disease in the
MRL.Faslpr lupus mouse model. While these data challenge the paradigm that NETs
promote lupus, it is conceivable that global regulatory properties of cybb and
cybb-independent NETs confound these findings. Furthermore, recent reports
indicate that inhibitors of peptidyl arginine deiminase, type IV (Padi4), a
distal mediator of NET formation, improve lupus in murine models. Here, to
clarify the contribution of NETs to SLE, we employed a genetic approach to delete
Padi4 in the MRL.Faslpr model and used a pharmacological approach to inhibit PADs
in both the anti-glomerular basement membrane model of proliferative nephritis
and a human-serum-transfer model of SLE. In contrast to prior inhibitor studies,
we found that deletion of Padi4 did not ameliorate any aspect of nephritis, loss
of tolerance, or immune activation. Pharmacological inhibition of PAD activity
had no effect on end-organ damage in inducible models of glomerulonephritis.
These data provide a direct challenge to the concept that NETs promote
autoimmunity and target organ injury in SLE.
PMID- 28515362
TI - Insulin supplementation attenuates cancer-induced cardiomyopathy and slows tumor
disease progression.
AB - Advanced cancer induces fundamental changes in metabolism and promotes cardiac
atrophy and heart failure. We discovered systemic insulin deficiency in cachectic
cancer patients. Similarly, mice with advanced B16F10 melanoma (B16F10-TM) or
colon 26 carcinoma (C26-TM) displayed decreased systemic insulin associated with
marked cardiac atrophy, metabolic impairment, and function. B16F10 and C26 tumors
decrease systemic insulin via high glucose consumption, lowering pancreatic
insulin production and producing insulin-degrading enzyme. As tumor cells consume
glucose in an insulin-independent manner, they shift glucose away from
cardiomyocytes. Since cardiomyocytes in both tumor models remained insulin
responsive, low-dose insulin supplementation by subcutaneous implantation of
insulin-releasing pellets improved cardiac glucose uptake, atrophy, and function,
with no adverse side effects. In addition, by redirecting glucose to the heart in
addition to other organs, the systemic insulin treatment lowered glucose usage by
the tumor and thereby decreased tumor growth and volume. Insulin corrected the
cancer-induced reduction in cardiac Akt activation and the subsequent
overactivation of the proteasome and autophagy. Thus, cancer-induced systemic
insulin depletion contributes to cardiac wasting and failure and may promote
tumor growth. Low-dose insulin supplementation attenuates these processes and may
be supportive in cardio-oncologic treatment concepts.
PMID- 28515363
TI - Lung CD103+ dendritic cells restrain allergic airway inflammation through IL-12
production.
AB - DCs are necessary and sufficient for induction of allergic airway inflammation.
CD11b+ DCs direct the underlying Th2 immunity, but debate surrounds the function
of CD103+ DCs in lung immunity and asthma after an allergic challenge. We
challenged Batf3-/- mice, which lacked lung CD103+ DCs, with the relevant
allergen house dust mite (HDM) as a model to ascertain their role in asthma. We
show that acute and chronic HDM exposure leads to defective Th1 immunity in Batf3
deficient mice. In addition, chronic HDM challenge in Batf3-/- mice results in
increased Th2 and Th17 immune responses and exacerbated airway inflammation.
Mechanistically, Batf3 absence does not affect induction of Treg or IL-10
production by lung CD4+ T cells following acute HDM challenge. Batf3-dependent
CD103+ migratory DCs are the main source of IL-12p40 in the mediastinal lymph
node DC compartment in the steady state. Moreover, CD103+ DCs selectively
increase their IL-12p40 production upon HDM administration. In vivo IL-12
treatment reverts exacerbated allergic airway inflammation upon chronic HDM
challenge in Batf3-/- mice, restraining Th2 and Th17 responses without triggering
Th1 immunity. These results suggest a protective role for lung CD103+ DCs to HDM
allergic airway inflammation through the production of IL-12.
PMID- 28515365
TI - Ceramide synthesis regulates T cell activity and GVHD development.
AB - Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective
immunotherapy for a variety of hematologic malignances, yet its efficacy is
impeded by the development of graft-versus-host disease (GVHD). GVHD is
characterized by activation, expansion, cytokine production, and migration of
alloreactive donor T cells. Hence, strategies to limit GVHD are highly desirable.
Ceramides are known to contribute to inflammation and autoimmunity. However,
their involvement in T-cell responses to alloantigens is undefined. In the
current study, we specifically characterized the role of ceramide synthase 6
(CerS6) after allo-HCT using genetic and pharmacologic approaches. We found that
CerS6 was required for optimal T cell activation, proliferation, and cytokine
production in response to alloantigen and for subsequent induction of GVHD.
However, CerS6 was partially dispensable for the T cell-mediated antileukemia
effect. At the molecular level, CerS6 was required for efficient TCR signal
transduction, including tyrosine phosphorylation, ZAP-70 activation, and
PKCtheta/TCR colocalization. Impaired generation of C16-ceramide was responsible
for diminished allogeneic T cell responses. Furthermore, targeting CerS6 using a
specific inhibitor significantly reduced T cell activation in mouse and human T
cells in vitro. Our study provides a rationale for targeting CerS6 to control
GVHD, which would enhance the efficacy of allo-HCT as an immunotherapy for
hematologic malignancies in the clinic.
PMID- 28515364
TI - Nicotinamide metabolism regulates glioblastoma stem cell maintenance.
AB - Metabolic dysregulation promotes cancer growth through not only energy
production, but also epigenetic reprogramming. Here, we report that a critical
node in methyl donor metabolism, nicotinamide N-methyltransferase (NNMT), ranked
among the most consistently overexpressed metabolism genes in glioblastoma
relative to normal brain. NNMT was preferentially expressed by mesenchymal
glioblastoma stem cells (GSCs). NNMT depletes S-adenosyl methionine (SAM), a
methyl donor generated from methionine. GSCs contained lower levels of
methionine, SAM, and nicotinamide, but they contained higher levels of oxidized
nicotinamide adenine dinucleotide (NAD+) than differentiated tumor cells. In
concordance with the poor prognosis associated with DNA hypomethylation in
glioblastoma, depletion of methionine, a key upstream methyl group donor, shifted
tumors toward a mesenchymal phenotype and accelerated tumor growth. Targeting
NNMT expression reduced cellular proliferation, self-renewal, and in vivo tumor
growth of mesenchymal GSCs. Supporting a mechanistic link between NNMT and DNA
methylation, targeting NNMT reduced methyl donor availability, methionine levels,
and unmethylated cytosine, with increased levels of DNA methyltransferases, DNMT1
and DNMT3A. Supporting the clinical significance of these findings, NNMT
portended poor prognosis for glioblastoma patients. Collectively, our findings
support NNMT as a GSC-specific therapeutic target in glioblastoma by disrupting
oncogenic DNA hypomethylation.
PMID- 28515366
TI - Experimental lupus is aggravated in mouse strains with impaired induction of
neutrophil extracellular traps.
AB - Many effector mechanisms of neutrophils have been implicated in the pathogenesis
of systemic lupus erythematosus (SLE). Neutrophil extracellular traps (NETs) have
been assigned a particularly detrimental role. Here we investigated the
functional impact of neutrophils and NETs on a mouse model of lupus triggered by
intraperitoneal injection of the cell death-inducing alkane pristane. Pristane
induced lupus (PIL) was aggravated in 2 mouse strains with impaired induction of
NET formation, i.e., NOX2-deficient (Ncf1-mutated) and peptidyl arginine
deiminase 4-deficient (PAD4-deficient) mice, as seen from elevated levels of
antinuclear autoantibodies (ANAs) and exacerbated glomerulonephritis. We observed
a dramatically reduced ability to form pristane-induced NETs in vivo in both Ncf1
mutated and PAD4-deficient mice, accompanied by higher levels of inflammatory
mediators in the peritoneum. Similarly, neutropenic Mcl-1DeltaMyelo mice
exhibited higher levels of ANAs, which indicates a regulatory function in lupus
of NETs and neutrophils. Blood neutrophils from Ncf1-mutated and human
individuals with SLE exhibited exuberant spontaneous NET formation. Treatment
with specific chemical NOX2 activators induced NET formation and ameliorated PIL.
Our findings suggest that aberrant NET is one of the factors promoting
experimental lupus-like autoimmunity by uncontrolled release of inflammatory
mediators.
PMID- 28515367
TI - Association of impaired neuronal migration with cognitive deficits in extremely
preterm infants.
AB - Many extremely preterm infants (born before 28 gestational weeks [GWs]) develop
cognitive impairment in later life, although the underlying pathogenesis is not
yet completely understood. Our examinations of the developing human neocortex
confirmed that neuronal migration continues beyond 23 GWs, the gestational week
at which extremely preterm infants have live births. We observed larger numbers
of ectopic neurons in the white matter of the neocortex in human extremely
preterm infants with brain injury and hypothesized that altered neuronal
migration may be associated with cognitive impairment in later life. To confirm
whether preterm brain injury affects neuronal migration, we produced brain damage
in mouse embryos by occluding the maternal uterine arteries. The mice showed
delayed neuronal migration, ectopic neurons in the white matter, altered neuronal
alignment, and abnormal corticocortical axonal wiring. Similar to human extremely
preterm infants with brain injury, the surviving mice exhibited cognitive
deficits. Activation of the affected medial prefrontal cortices of the surviving
mice improved working memory deficits, indicating that decreased neuronal
activity caused the cognitive deficits. These findings suggest that altered
neuronal migration altered by brain injury might contribute to the subsequent
development of cognitive impairment in extremely preterm infants.
PMID- 28515369
TI - Effect of Reverse Vessel Remodeling on Regression of Coronary Atherosclerosis in
Patients Treated With Aggressive Lipid- and Blood Pressure-Lowering Therapy -
Insight From MILLION Study.
AB - BACKGROUND: The MILLION study, a prospective randomized multicenter study,
revealed that lipid and blood pressure (BP)-lowering therapy resulted in
regression of coronary plaque as determined by intravascular ultrasound (IVUS).
In the present study we performed additional analysis to investigate the
associated factors with regression of coronary plaque.Methods and Results:We
investigated serial 3D IVUS images from 68 patients in the MILLION study.
Standard IVUS parameters were assessed at both baseline and follow-up (18-24
months). Volumetric data were standardized by length as normalized volume. In
patients with plaque regression (n=52), plaque volumenormalizedsignificantly
decreased from 64.8 to 55.8 mm3(P<0.0001) and vessel
volumenormalizedsignificantly decreased from 135.0 to 127.5 mm3(P=0.0008). There
was no difference in lumen volumenormalizedfrom 70.1 to 71.8 mm3(P=0.27). There
were no correlations between % changes in vessel volume and cholesterol or BP. On
the other hand, negative correlations between % change in vessel volume and
vessel volumenormalizedat baseline (r=-0.352, P=0.009) or plaque
volumenormalizedat baseline (r=-0.336, P=0.01) were observed. CONCLUSIONS: The
current data demonstrated that in patients with plaque regression treated by
aggressive lipid and BP-lowering therapy, the plaque regression was derived from
reverse vessel remodeling determined by vessel volume and plaque burden at
baseline irrespective of decreases in lipids and BP.
PMID- 28515370
TI - Acute Kidney Injury Following Cardiopulmonary Bypass in Children - Risk Factors
and Outcomes.
AB - BACKGROUND: Acute kidney injury (AKI) is the most common and most serious
complication following heart surgery. We aimed to determine the prevalence of,
and risk factors for, AKI following pediatric cardiac surgery.Methods and
Results:We retrospectively analyzed 135 patients aged <=18 years who underwent
cardiac surgery for congenital heart defects; by RACHS-1 category, 58 patients
(43%) had an operative risk score >=3. AKI was defined and classified using the
pediatric pRIFLE criteria (Pediatric Risk, Injury, Failure, Loss, and End-stage
Kidney Disease); 19 patients (14.1%) developed AKI: 17 had AKI with a severity
classified as risk (R) and 2 had AKI classified as injury (I). Body weight,
height, body surface area, and preoperative mechanical ventilation were all
independently associated with AKI development (P=0.038, 0.040, 0.033 and 0.008,
respectively). Preoperative ventilation strongly correlated with AKI severity.
Higher pRIFLE classification positively correlated with increased incidence of
peritoneal dialysis, increased postoperative mechanical ventilation duration, and
longer hospital stay (P=0.009, 0.039 and 0.042, respectively). CONCLUSIONS: In
this study, we found a low prevalence of postoperative AKI in pediatric patients
undergoing severe cardiac surgery. AKI was associated with worse early
postoperative outcomes. Early prediction and appropriate treatment of AKI during
the postoperative period are emphasized.
PMID- 28515371
TI - Bilateral cervical ribs in a mixed breed dog.
AB - A 4-year-old intact female, mixed breed dog was presented with a complaint of
dyspnea. Clinical examination revealed symptoms related to disease of the upper
airways. Radiographic findings were consistent with tracheal collapse associated
with anomalies involving the seventh cervical vertebra and the first ribs
bilaterally. Radiographs were highly suggestive of cervical ribs; computed
tomography and ultrasound examination allowed complete characterization and
better localization of the anomalies with relationship to the adjacent muscle and
vasculature. Cervical ribs are malformations widely described in human medicine,
but only sporadically in dogs. Herein, we discuss etiological, clinical,
diagnostic and therapeutic aspects of cervical ribs and possible correlations
between the cervical ribs and other anatomical anomalies noted in this dog.
PMID- 28515372
TI - Spinal Arteriovenous Shunts: Angioarchitecture and Historical Changes in
Classification.
AB - The purposes of this study were to review historical changes in the
classification of spinal arteriovenous (AV) shunts and to propose a practical
classification system. The associated literature regarding the classification of
spinal AV shunts was reviewed in the angiography era between 1967 and 2015. The
classification systems of spinal AV shunts and a proposed classification system
were presented with neuroradiological imaging and medical illustrations. There
have been seven major classification systems based on the evolution of diagnostic
methods as well as treatments for spinal AV shunts: the first description of
spinal AV shunts diagnosed and classified using spinal angiography in 1971; the
second classification based on a case report of intradural direct perimedullary
arteriovenous fistulas (AVFs) treated by microsurgery in 1987; the third
classification based on a case series of intradural perimedullary AVFs treated by
endovascular interventions in 1993; the fourth and fifth classification systems
based on a case series of spinal AVFs and arteriovenous malformations (AVMs)
treated by microsurgery or endovascular interventions in 2002; the sixth
classification based on a case series of cranio-spinal dural AV shunts in 2009;
and the seventh classification based on a case series of extradural AVFs treated
by microsurgery and endovascular interventions in 2011. Based on historical
reports, the author proposed a classification system according to the sites
(dural, intradural, and extradural) and types (AVF and AVM) of AV shunts. By
learning the historical background, we may obtain a clearer understanding of the
complex and confusing classification system of spinal AV shunts.
PMID- 28515373
TI - How accurately does the Brief Job Stress Questionnaire identify workers with or
without potential psychological distress?
AB - OBJECTIVES: The manual for the Japanese Stress Check Program recommends use of
the Brief Job Stress Questionnaire (BJSQ) from among the program's instruments
and proposes criteria for defining "high-stress" workers. This study aimed to
examine how accurately the BJSQ identifies workers with or without potential
psychological distress. METHODS: We used an online survey to administer the BJSQ
with a psychological distress scale (K6) to randomly selected workers (n=1,650).
We conducted receiver operating characteristics curve analyses to estimate the
screening performance of the cutoff points that the Stress Check Program manual
recommends for the BJSQ. RESULTS: Prevalence of workers with potential
psychological distress defined as K6 score >=13 was 13%. Prevalence of "high
risk" workers defined using criteria recommended by the program manual was 16.7%
for the original version of the BJSQ. The estimated values were as follows:
sensitivity, 60.5%; specificity, 88.9%; Youden index, 0.504; positive predictive
value, 47.3%; negative predictive value, 93.8%; positive likelihood ratio, 6.0;
and negative likelihood ratio, 0.4. Analyses based on the simplified BJSQ
indicated lower sensitivity compared with the original version, although we
expected roughly the same screening performance for the best scenario using the
original version. CONCLUSIONS: Our analyses in which psychological distress
measured by K6 was set as the target condition indicate less than half of the
identified "high-stress" workers warrant consideration for secondary screening
for psychological distress.
PMID- 28515374
TI - Polyphyllin I Overcomes EMT-Associated Resistance to Erlotinib in Lung Cancer
Cells via IL-6/STAT3 Pathway Inhibition.
AB - Acquired resistance to epidermal growth factor receptor tyrosine kinase
inhibitors (EGFR-TKIs) is the most important limiting factor for treatment
efficiency in EGFR-mutant non-small cell lung cancer (NSCLC). Much work has
linked the epithelial-mesenchymal transition (EMT) to the emergence of drug
resistance, consequently, ongoing research has been focused on exploring the
therapeutic options to reverse EMT for delaying or preventing drug resistance.
Polyphyllin I (PPI) is a natural compound isolated from Paris polyphylla rhizomes
and displayed anti-cancer properties. In the current work, we aimed to testify
whether PPI could reverse EMT and overcome acquired EGFR-TKI resistance. We
exposed HCC827 lung adenocarcinoma cells to erlotinib which resulted in acquired
resistance with strong features of EMT. PPI effectively restored drug sensitivity
of cells that obtained acquired resistance. PPI reversed EMT and decreased
interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3)
signaling pathway activation in erlotinib-resistant cells. Moreover, addition of
IL-6 partially abolished the sensitization response of PPI. Furthermore, co
treatment of erlotinib and PPI completed abrogation of tumor growth in
xenografts, which was associated with EMT reversal. In conclusion, PPI serves as
a novel solution to conquer the EGFR-TKI resistance of NSCLC via reversing EMT by
modulating IL-6/STAT3 signaling pathway. Combined PPI and erlotinib treatment
provides a promising future for lung cancer patients to strengthen drug response
and prolong survival.
PMID- 28515376
TI - Carotenoids of Red, Brown, and Black Specimens of Plectropomus leopardus, the
Coral Trout (Suziara in Japanese).
AB - This study investigated the carotenoids occurring in the integument of
Plectropomus leopardus, the coral trout. For a red specimen, the major
carotenoids included astaxanthin diester and monoester, as well as alpha
cryptoxanthin ester, tunaxanthin diester, adonixanthin diester, adonirubin ester,
and adonirubin; for brown and black specimens, tunaxanthin diester was the main
carotenoid. 1H-NMR and MS spectral analyses showed that docosahexaenoic acid was
the sole fatty acid esterified with xanthophylls in the coral trout.
PMID- 28515375
TI - Modified Gas Chromatographic Method to Determine Monoacylglycerol and
Diacylglycerol Contents in Edible Fats and Oils.
AB - Monoacylglycerol (MAG) and diacylglycerol (DAG) are minor components of edible
fats and oils, and they relate to the quality of these foods. The AOCS official
method Cd 11b-91 has been used to determine MAG and DAG contents in fats and
oils. There are, however, difficulties in the determination of MAG and DAG using
this analytical procedure. Therefore, we improved this method by modifying the
trimethylsilyl derivatization procedure and replacing the internal standard (IS)
material. In our modified method, TMS-HT (mixture of hexamethyldisilazane and
trimethylchlorosilane) was used for derivatization of MAG and DAG, which was
followed by liquid-liquid extraction with water and n-hexane solution containing
the IS, tricaprin. Using the modified method, we demonstrated superior
repeatability in comparison with that of the AOCS method by reducing procedural
difficulties. The relative standard deviation of distearin peak areas was 1.8% or
2.9% in the modified method, while it was 5.6% in the AOCS method. In addition,
capillary columns, such as DB-1ht and DB-5ht could be used in this method.
PMID- 28515377
TI - High-fat Diet Increases Phospholipid Peroxidation in the Liver of Mature Fischer
344 Rats.
AB - Phospholipid peroxidation is considered to be involved in the pathophysiology of
various diseases. While dietary antioxidants are believed to help prevent these
diseases via inhibition of phospholipid peroxidation, further evaluation is
needed to prove this hypothesis. For this, it is crucial to establish an animal
model with accelerated phospholipid peroxidation. In this study, we hypothesized
that a combination of aging and high-fat diet feeding may accelerate phospholipid
peroxidation in vivo. High-fat diets were fed to mature and juvenile Fischer 344
rats for 12 weeks. The mature rats in particular accumulated body fat and liver
phosphatidylcholine hydroperoxide (PCOOH). Interestingly, the increase in PCOOH
levels was abrogated by the co-administration of antioxidants to mature rats.
This may be attributed to factors including the decrease in body fat, functions
of vitamin E, and/or the involvement of antioxidant-related genes, each caused by
antioxidant administration. These results indicate that the high-fat diet-fed
aging animal model may be suitable for investigation of the relationship between
phospholipid peroxidation, oxidative stress-related diseases, and dietary
antioxidants.
PMID- 28515378
TI - Direct Involvement of Arachidonic Acid in the Development of Ear Edema via TRPV3.
AB - Arachidonic acid (AA) plays a pivotal role in the development of edema via its
oxidized metabolites derived from cyclooxygenase (COX) and lipoxygenase (LOX),
and is recently recognized as an activator of TRPV3. However, it is not clear
whether AA plays some TRPV3-mediated pathological roles in the development of
edema. Pharmacological and histological studies using ICRTRPV3+/+ and ICRTRPV3-/-
mice indicated that higher ear edema responses to topical application of AA were
observed in ICRTRPV3+/+ mice compared with ICRTRPV3-/- mice. However, there was
no difference in the ear edema response to 12-O-tetradecanoylphorbol 13-acetate,
skin histology, and skin barrier function between these mouse strains.
Furthermore, oxidized fatty acids from the lesional site were analyzed to
elucidate the TRPV3-mediated pathological roles of AA, and the results revealed
that there were no differences in the level of COX or LOX metabolites derived
from AA between both mouse strains. We concluded that AA plays a role in the
development of TRPV3-mediated ear edema and that this result may contribute to
better understanding of the pathophysiological mechanisms involved in the
development of a certain type of edema.
PMID- 28515379
TI - Alternative Internal Standard Calibration of an Indirect Enzymatic Analytical
Method for 2-MCPD Fatty Acid Esters.
AB - An indirect enzymatic analysis method for the quantification of fatty acid esters
of 2-/3-monochloro-1,2-propanediol (2/3-MCPD) and glycidol was developed, using
the deuterated internal standard of each free-form component. A statistical
method for calibration and quantification of 2-MCPD-d5, which is difficult to
obtain, is substituted by 3-MCPD-d5 used for calculation of 3-MCPD. Using data
from a previous collaborative study, the current method for the determination of
2-MCPD content using 2-MCPD-d5 was compared to three alternative new methods
using 3-MCPD-d5. The regression analysis showed that the alternative methods were
unbiased compared to the current method. The relative standard deviation (RSDR)
among the testing laboratories was <= 15% and the Horwitz ratio was <= 1.0, a
satisfactory value.
PMID- 28515380
TI - Highly Selective and Considerable Subcritical Butane Extraction to Separate
Abamectin in Green Tea.
AB - We specially carried out the subcritical butane extraction to separate abamectin
from tea leaves. Four parameters, such as extraction temperature, extraction
time, number of extraction cycles, and solid-liquid ratio were studied and
optimized through the response surface methodology with design matrix developed
by Box-Behnken. Seventeen experiments with three various factors and three
variable levels were employed to investigate the effect of these parameters on
the extraction of abamectin. Besides, catechins, theanine, caffeine, and aroma
components were determined by both high-performance liquid chromatography and gas
chromatography-mass spectrometry to evaluate the tea quality before and after the
extraction. The results showed that the extraction temperature was the uppermost
parameter compared with others. The optimal extraction conditions selected as
follows: extraction temperature, 42 degrees C; number of extraction cycles and
extraction time, 1 and 30 min, respectively; and solid-liquid ratio, 1:10. Based
on the above study, the separation efficiency of abamectin was up to 93.95%. It
is notable that there has a quite low loss rate, including the negligible damage
of aroma components, the bits reduce of catechins within the range of 0.7%-13.1%,
and a handful lessen of caffeine and theanine of 1.81% and 2.6%, respectively.
The proposed method suggested subcritical butane possesses solubility for lipid
soluble pesticides, and since most of the pesticides are attached to the surfaces
of tea, thus the as-applied method was successfully effective to separate
abamectin because of the so practical and promising method.
PMID- 28515381
TI - Preliminary Evaluation of Glyceric Acid-producing Ability of Acidomonas
methanolica NBRC104435 from Glycerol Containing Methanol.
AB - Some acetic acid bacteria produce large amounts of glyceric acid (GA) from
glycerol in culture broth. However, methanol, which is a major contaminant of raw
glycerol derived from the biodiesel fuel industry, sharply decreases cell growth
and GA production [AMB Express, 3, 20, 2013]. Thus, we evaluated the
methylotrophic acetic acid bacterium Acidomonas methanolica NBRC104435 for its
ability to produce GA from glycerol containing methanol. This strain accumulated
GA in its culture broth when 1-3 wt% glycerol was available as a carbon source.
We observed improved cell growth and GA accumulation when 1 vol% methanol was
added to the 3-5 wt% glycerol medium. The maximum concentration of GA was 12.8
g/L in medium containing 3 wt% glycerol plus 1 vol% methanol. In addition, the
enantiomeric excess (ee) of the GA produced was revealed to be 44%, indicating
that this strain converted glycerol to d-GA with a lower enantioselectivity than
other acetic acid bacteria, which had 70-99% ee.
PMID- 28515382
TI - Screening Evaluation of the Interaction of Linear-Chain or Branched-Chain
Peptides with Multilamellar Vesicle, Using Confocal Laser Microscopy.
AB - In the present research, we prepared an acidic liposome as a cell model and used
confocal laser microscopy to evaluate its interaction with oligopeptides that had
high membrane permeability or affinity. The results showed that, for short
peptides of about ten residues, the positive charge peptides interacted with the
acidic liposome strongly. For peptides that interacted with the liposome, no
difference was found between linear-chain and branched-chain peptides due to
their structure.
PMID- 28515383
TI - A New Agonist for Peroxisome Proliferation-activated Receptor gamma (PPARgamma),
Fraglide-1 from Zhenjiang Fragrant Vinegar: Screening and Characterization Based
on Cell Culture Experiments.
AB - Zhenjiang fragrant vinegar (Kozu) is a black rice vinegar that has been used as a
traditional Chinese medicine and has various health benefits, including anti
obesity effects. In the present study, using luciferase reporter assays of
PPARgamma promoter activity, a novel ingredient from 8-year-old Kozu, 5-hydroxy-4
phenyl-butenolide, was isolated. The newly found agonist was named as "Fraglide
1". Moreover, in subsequent experiments, it was confirmed that fraglide-1 was an
PPARgamma agonist and it could increase expression level of the uncoupling
protein (UCP)-1. Fraglide-1 was chemically synthesized and it was verified that
expression of the PPARgamma was increased in dose dependent manner. Although Kozu
has been consumed globally as a functional food for thousands of years, the
mechanisms behind its health effects have not been characterized. The active
ingredient of Kozu was successfully found and the results unraveled a longtime
mystery about Kozu for its beneficial health effect.
PMID- 28515384
TI - Physicochemical and Antioxidant Properties of Rice Bran Oils Produced from
Colored Rice Using Different Extraction Methods.
AB - This study investigated the physicochemical and antioxidant properties of rice
bran oil (RBO) produced from the bran of three rice varities; Khao Dawk Mali 105
(white rice), Red Jasmine rice (red rice) and Hom-nin rice (black rice) using
three extraction methods including cold-press extraction (CPE), solvent
extraction (SE) and supercritical CO2 extraction (SC-CO2). Yields, color, acid
value (AV), free fatty acid (FFA), peroxide value (PV), iodine value (IV), total
phenolic compound (TPC), gamma-oryzanol, alpha-tocopherol and fatty acid profile
were analyzed. It was found that the yields obtained from SE, SC-CO2 and CPE
extractions were 17.35-20.19%, 14.76-18.16% and 3.22-6.22%, respectively. The RBO
from the bran of red and black rice samples exhibited high antioxidant
activities. They also contained higher amount of gamma-oryzanol and alpha
tocopherol than those of white rice sample. In terms of extraction methods, SC
CO2 provided better qualities of RBO as evidenced by their physicochemical and
antioxidant properties. This study found that RBO produced from the bran of black
rice samples using SC-CO2 extraction method showed the best physicochemical and
antioxidant properties.
PMID- 28515385
TI - Supercritical CO2 Extraction of Rice Bran Oil -the Technology, Manufacture, and
Applications.
AB - Rice bran is a good source of nutrients that have large amounts of phytochemicals
and antioxidants. Conventional rice bran oil production requires many processes
that may deteriorate and degrade these valuable substances. Supercritical CO2
extraction is a green alternative method for producing rice bran oil. This work
reviews production of rice bran oil by supercritical carbon dioxide (SC-CO2)
extraction. In addition, the usefulness and advantages of SC-CO2 extracted rice
bran oil for edible oil and health purpose is also described.
PMID- 28515386
TI - Autoxidation of Fish Oil Blended with Rice Bran Oil.
AB - Effects of rice bran oil on the oxidative and flavor stability of fish oil were
investigated by the gas liquid chromatography-head space method. When fish oil
blending with different ratio of rice bran oils was oxidized at room temperature
in the dark, volatile compounds produced during autoxidation was measured by gas
liquid chromatography. The amounts of volatile compounds were decreased with
increased the ratio of blended rice bran oil as well as peroxide value. The level
of propanal and acrolein which gave unpleasant flavor was also decreased with
increased the ratio of blended rice bran oil. Especially, the level of propanal
and acrolein and peroxide value were remarkably decreased when blending more than
75% of rice bran oil. Blending of rice bran oil improved the oxidative and flavor
stabilities of fish oil.
PMID- 28515387
TI - Functional polymorphisms affecting Th1 differentiation are associated with the
severity of autoimmune thyroid diseases.
AB - The prognosis for autoimmune thyroid diseases (AITDs), such as Hashimoto's
disease (HD) and Graves' disease (GD), varies among patients. Interleukin (IL)-12
and IL-18 also induce Th1 differentiation, and SOCS1 (Suppressor of cytokine
signaling 1) and TIM-3 (T cell immunoglobulin and mucin domain-3) are known to be
negative regulators of Th1 cells. To clarify the association of functional
polymorphisms in the IL12, IL12Rbeta1, IL18, SOCS1 and TIM3 genes with the
intractability and severity of autoimmune thyroid disease (AITD), we genotyped
these polymorphisms in 151 GD patients, including 61 patients with intractable GD
and 51 patients with GD in remission, in 140 HD patients, including 59 patients
with severe HD and 55 patients with mild HD, and in 74 healthy controls. The
frequency of the IL18 -607CC genotype which correlates with a high production of
IL-18, was significantly higher in patients with GD in remission than in those
with intractable GD (p=0.0178). The -607C allele was significantly higher in
patients with severe HD than in those with mild HD (p=0.0050). The -607CC
genotype in IL18 gene may be protective against the intractability of GD, and the
-607C allele may enhance the severity of HD.
PMID- 28515388
TI - Nitric oxide is critical for avoiding hepatic lipid overloading via IL-6
induction during liver regeneration after partial hepatectomy in mice.
AB - Nitric oxide (NO), generated from L-arginine by three different isoforms of
nitric oxide synthase (NOS), is a pleiotropic factor to regulate physiological
functions in almost every organ and tissue. Each knockout mouse of iNOS or eNOS
has been used to suggest that NO has a crucial role in liver regeneration after
partial hepatectomy (PH), for NO may inhibit caspase 3 activity and is required
for EGFR signaling. In previous reports, defective mitochondrial beta-oxidation
was observed in eNOS KO mice, and hepatic steatosis was often correlated to
deficient liver regeneration, so we focused on metabolic perspective and
hypothesized that NO depletion in PH mice would affect hepatocytic lipolysis and
impair hepatocytes proliferation. We inhibited all NOS isoforms by administrating
L-NG-nitroarginine methyl ester (L-NAME) to PH mice, and hepatocyte DNA synthesis
was severely inhibited at 40-44 h post PH in L-NAME (+) group. IL-6 was robustly
secreted into circulating blood in L-NAME (-) group, but not in L-NAME (+) group.
Down-regulation of carnitine palmytoyltransferase 1A, massive lipid accumulation
and elevated endoplasmic reticulum (ER) stress relative genes expression level
were observed in L-NAME (+) group mouse liver. The expression level of C/EBP
homologous protein, a mediator of ER stress induced apoptosis, significantly
increased in L-NAME (+) group. Our findings suggest the lack of NO affected IL-6
induction and hepatocyte lipolysis after PH, consequently leading to excessive
hepatic lipid accumulation, elevated ER stress and impaired hepatocyte
proliferation.
PMID- 28515389
TI - Ca2+ in Hybridization Solutions for Fluorescence in situ Hybridization
Facilitates the Detection of Enterobacteriaceae.
AB - Fluorescence in situ hybridization (FISH) has been employed to identify
microorganisms at the single cell level under a microscope. Extensive efforts
have been made to improve and extend the FISH technique; however, the development
of a widely applicable protocol is a continuing challenge. The present study
evaluated the effects of divalent cations in the hybridization solution on the
FISH-based detection of various species of bacteria and archaea with rRNA
targeted probes. A flow cytometric analysis after FISH with a standard
hybridization buffer detected positive signals from less than 30% of Escherichia
coli IAM 1264 cells. However, the number of cells with positive signals increased
to more than 90% after the addition of calcium chloride to the hybridization
buffer. Mn2+ also had positive effects, whereas Mg2+ did not. The positive
effects of Ca2+ were similarly observed for bacteria belonging to
Enterobacteriaceae, including Enterobacter sakazakii IAM 12660T, E. aerogenes IAM
12348, Klebsiella planticola IAM 14202, and Salmonella enterica subsp. enterica
serovar Typhimurium strain LT2. These results indicate that the supplementation
of Ca2+ to the hybridization buffer for FISH contributes to the efficient
detection of Enterobacteriaceae cells.
PMID- 28515390
TI - Biocontrol Potential of an Endophytic Streptomyces sp. Strain MBCN152-1 against
Alternaria brassicicola on Cabbage Plug Seedlings.
AB - In the present study, 77 strains of endophytic actinomycetes isolated from
cabbage were screened in order to assess their biocontrol potential against
Alternaria brassicicola on cabbage seedlings. In the first and second screening
trials, cabbage seedlings pretreated with mycelial suspensions of each isolate
were spray-inoculated with A. brassicicola. Strain MBCN152-1, which exhibited the
best protection in screening trials and had no adverse effects on seedling
growth, was selected for the greenhouse trial. In the greenhouse trial, cabbage
seedlings, which had been grown in plug trays filled with soil mix containing
spores of MBCN152-1 (1*108 spores g-1 of soil mix), were spray-inoculated with A.
brassicicola and grown in greenhouse conditions. MBCN152-1 reduced disease
incidence and significantly increased the number of viable seedlings. The
efficacy of MBCN152-1 against damping-off caused by seed-borne A. brassicicola
was then evaluated. Cabbage seeds, artificially infested with A. brassicicola,
were sown in soil mix containing MBCN152-1 spores. The disease was completely
suppressed when infested seeds were sown in a soil mix blended with MBCN152-1 at
1.5*107 spores g-1 of soil mix. These results strongly suggest that MBCN152-1 has
the potential to control A. brassicicola on cabbage plug seedlings. MBCN152-1 was
identified as a Streptomyces humidus-related species based on 16S rDNA
sequencing. Scanning electron microscopy showed that the hyphae of MBCN152-1
multiplied on the surface of the seedlings and penetrated their epidermal cells.
In conclusion, strain MBCN152-1 is a promising biocontrol agent against A.
brassicicola on cabbage plug seedlings.
PMID- 28515392
TI - Assessment of Left Ventricular Function and Mass on Free-Breathing Compressed
Sensing Real-Time Cine Imaging.
AB - BACKGROUND: Compressed sensing (CS) cine magnetic resonance imaging (MRI) has the
advantage of being inherently insensitive to respiratory motion. This study
compared the accuracy of free-breathing (FB) CS and breath-hold (BH) standard
cine MRI for left ventricular (LV) volume assessment.Methods and Results:Sixty
three patients underwent cine MRI with both techniques. Both types of images were
acquired in stacks of 8 short-axis slices (temporal/spatial resolution, 41
ms/1.7*1.7*6 mm3) and compared for ejection fraction, end-diastolic and systolic
volumes, stroke volume, and LV mass. Both BH standard and FB CS cine MRI provided
acceptable image quality for LV volumetric analysis (score >=3) in all patients
(4.7+/-0.5 and 3.7+/-0.5, respectively; P<0.0001) and had good agreement on LV
functional assessment. LV mass, however, was slightly underestimated on FB CS
cine MRI (median, IQR: BH standard, 83.8 mL, 64.7-102.7 mL; FB CS, 79.0 mL, 66.0
101.0 mL; P=0.0006). The total acquisition times for BH standard and FB CS cine
MRI were 113+/-7 s and 24+/-4 s, respectively (P<0.0001). CONCLUSIONS: Despite
underestimation of LV mass, FB CS cine MRI is a clinically useful alternative to
BH standard cine MRI in patients with impaired BH capacity.
PMID- 28515391
TI - Advanced glycation end products regulate interleukin-1beta production in human
placenta.
AB - Maternal obesity is a major risk factor for pregnancy complications, causing
inflammatory cytokine release in the placenta, including interleukin-1beta (IL
1beta), IL-6, and IL-8. Pregnant women with obesity develop accelerated systemic
and placental inflammation with elevated circulating advanced glycation end
products (AGEs). IL-1beta is a pivotal inflammatory cytokine associated with
obesity and pregnancy complications, and its production is regulated by NLR
family pyrin domain-containing 3 (NLRP3) inflammasomes. Here, we investigated
whether AGEs are involved in the activation of NLRP3 inflammasomes using human
placental tissues and placental cell line. In human placental tissue cultures,
AGEs significantly increased IL-1beta secretion, as well as IL-1beta and NLRP3
mRNA expression. In human placental cell culture, although AGE treatment did not
stimulate IL-1beta secretion, AGEs significantly increased IL-1beta mRNA
expression and intracellular IL-1beta production. After pre-incubation with AGEs,
nano-silica treatment (well known as an inflammasome activator) increased IL
1beta secretion in placental cells. However, after pre-incubation with
lipopolysaccharide to produce pro-IL-1beta, AGE treatment did not affect IL-1beta
secretion in placental cells. These findings suggest that AGEs stimulate pro-IL
1beta production within placental cells, but do not activate inflammasomes to
stimulate IL-1beta secretion. Furthermore, using pharmacological inhibitors, we
demonstrated that AGE-induced inflammatory cytokines are dependent on MAPK/NF
kappaB/AP-1 signaling and reactive oxygen species production in placental cells.
In conclusion, AGEs regulate pro-IL-1beta production and inflammatory responses,
resulting in the activation of NLRP3 inflammasomes in human placenta. These
results suggest that AGEs, as an endogenous and sterile danger signal, may
contribute to chronic placental cytokine production.
PMID- 28515394
TI - CROSS-TALK BETWEEN IMMUNE SYSTEM AND BRAIN.
PMID- 28515393
TI - PHENOTYPE OF ALLERGIC RHINITIS AND RHINOSINUSITIS.
PMID- 28515395
TI - THE INTERRELATIONSHIP BETWEEN ASTHMA AND BRAIN ACTIVITIES: PSYCHOLOGICAL STRESS
RELATED ASTHMA AS A NEW ASTHMA PHENOTYPE.
PMID- 28515396
TI - JAPANESE GUIDELINE FOR OCCUPATIONAL ALLERGIC DISEASES 2016.
PMID- 28515397
TI - AIRWAY INFLAMMATION IN ASTHMA.
PMID- 28515398
TI - EXPERIMENTAL EVIDENCES FOR LOCAL ALLERGIC RHINITIS.
PMID- 28515399
TI - CROSS TALK OF INNATE AND ACQUIRED IMMUNITY IN ALLERGY.
PMID- 28515400
TI - THE ROLE OF MyD88 SIGNALING IN IgE RESPONSES IN LUNGS.
PMID- 28515401
TI - BASIC ACT ON ALLERGIC DISEASES MEASURES AND EQUALIZATION OF MEDICAL CARE IN
ALLERGIC DISEASES THROUGHOUT THE JAPAN.
PMID- 28515402
TI - DIFFERENCES IN FRACTION OF EXHALED NITRIC OXIDE VALUES MEASURED BY TWO HAND
HELDED ANALYZERS (NObreath(r) AND NIOX Vero(r)).
AB - BACKGROUND: The fraction of exhaled nitric oxide (FENO) is a useful marker of
asthma control. The FENO measurement with two hand-helded analyzers (NObreath(r)
and NIOX Vero(r)) may be more affordable, no studies have examined the
differences in FENO values measured with those methods in adult. METHODS: The
study population comprised 44 subjects at our outpatient clinic. FeNO values
(FENOb and FENOv) were measured by two methods (NObreath(r) and NIOX Vero(r)).
RESULTS: FENOb values were significantly correlated with FENOv (r = 0.911, p <
0.001). However, FENOv values were high compared with FENOb (FENOv = 1.40 *
FENOb). CONCLUSION: Differences exist in the values of FENO measured by two hand
helded analyzers: conversion equations are needed to compare the FENO values
between these methods.
PMID- 28515403
TI - ANALYSIS OF WHEAT ALLERGEN DISPERSED IN AIR BY THE ACTION OF THREE TYPES OF FLOUR
SIFTER.
AB - BACKGROUND: Since wheat flour, a cause of food allergy, tends to disperse rapidly
in air, it can unintentionally mix other foods during the sieving process. Our
aim was to analyze the dispersal of wheat flour dust in air in order to prevent
unintentional mixing. METHODS: We measured particle size distribution of wheat
flour, photographed the scattered flour for 60 seconds every 10 seconds after
sieving through three types of flour sifter, constructed a velocity vector
diagram of flour dust dispersal by each type of sifter, and measured the distance
of wheat allergen dispersal over 20 minutes using a petri dish and
immunochromatographic test. RESULTS: The particles were mainly 14.2MUm and
60.4MUm in diameter and settled at terminal velocities of about 8mm/s and
150mm/s, respectively. Wheat flour particles of more than 60MUm (released in air
by sifting) dropped mainly in the perpendicular direction, while particles of
less than 30MUm remained suspended and traveled 5m after sifting by all flour
sifters. CONCLUSION: Our results suggested that wheat flour dust dispersed by
sifting (regardless of sifter) could unintentionally mix other foods. To prevent
contamination, it is necessary to control the flow of air or sift flour in a
separate room.
PMID- 28515404
TI - INSOLUBILITY AND ALTERATION OF ALLERGENIC ACTIVITY OF WHEAT PROTEINS IN PROCESSED
FOODS.
AB - BACKGROUND: Food processing causes decomposition, denaturation or polymerization
of protein, which may alter an allergic reaction. This study aimed to investigate
the insolubility and alteration of wheat allergens in processed foods and the
reactivity to patient sera. METHODS: We extracted proteins from wheat flour, udon
and bread using different extracts and conducted SDS-polyacrylamide gel
electrophoresis. IgE-immunoblotting was also conducted using sera from children
with wheat allergy. RESULTS: Soluble protein was extracted from wheat flour, and
gluten fractions were also extracted by adding SDS. However, no proteins were
able to be extracted from udon or bread witout severing the disulfide bonds under
reducing condition. Only trace amounts of protein were detected in the water
after boiling udon noodles. The reactivity of IgE antibody to the extracted
protein did not differ among the different processed food types. CONCLUSIONS:
Wheat allergens became strongly insolubilized after gluten formation and heating.
However, the reactivity of IgE antibody to each allergen was not affected by food
processing. Further studies are needed for the effects on clinical symptoms.
PMID- 28515406
TI - Innate lymphoid cell (ILC) 3.
PMID- 28515405
TI - A CASE OF BRONCHIAL ASTHMA WITH HYPEREOSINOPHILIA WITH EFFECTIVE SAIBOKUTOU
THERAPY.
AB - A 42 year old woman visited on our hospital because of cough, sputum, pruritus
and erythema. She showed peripheral blood eosinophilia, high level of FENO,
bronchial hyperresponsiveness. Diagnosis of bronchial asthma and atopic
dermatitis was made, but she rejected therapy except for Saibokutou, a Kampo
herbal medicine. After 1 year, her symptoms and her laboratory data were
improved.
PMID- 28515408
TI - Variable Distribution of Pseudolobules in Ovarian Sclerosing Stromal Tumors:
Utility of Diffusion-weighted Imaging for Differential Diagnosis.
PMID- 28515407
TI - Comparison of the OUTBACK(r) Elite Reentry Catheter and the Bi-directional
Approach after Failed Antegrade Approach for Femoro-popliteal Occlusive Disease.
AB - AIM: A successful antegrade wire crossing for femoro-popliteal chronic total
occlusion (FP-CTO) is still a technical challenge. We attempted to demonstrate
the safety and feasibility of the OUTBACK(r) Elite reentry catheter and the bi
directional approach for failed FP-CTO cases with the antegrade approach.
METHODS: Endovascular therapy for FP-CTO was performed in 219 lesions from May
2013 to December 2016 at Morinomiya Hospital. We retrospectively analyzed the
data of 43 consecutive lesions which underwent endovascular therapy using the bi
directional approach with distal access and the mono-directional approach with
the OUTBACK(r) Elite reentry catheter for FP-CTO lesions. The antegrade success
using a combination of traditional and Intravascular Ultrasound (IVUS) -guided
techniques was achieved in 170 lesions out of a total of 219 lesions. From May
2013 to June 2016 (phase 1), the bi-directional approach with distal access was
applied to 22 lesions after failed antegrade approaches. From July 2016 to
December 2016 (phase 2), the mono-directional approach with the OUTBACK(r) Elite
reentry catheter was applied to 21 lesions. RESULTS: Clinical and lesion
characteristics in phase 1 were not significantly different from those in phase
2. The overall initial technical success rate was 100% in both phases. The total
wire number and amount of contrast media were significantly less, and the total
procedure time and the total fluoroscopic time were significantly shorter in
phase 2 than in phase 1 (p<0.01). CONCLUSIONS: Endovascular therapy for FP-CTO
using the OUTBACK(r) Elite reentry catheter is feasible and safe after a failed
antegrade approach.
PMID- 28515409
TI - Saturation Recovery Myocardial T1 Mapping with a Composite Radiofrequency Pulse
on a 3T MR Imaging System.
AB - PURPOSE: To evaluate the effect of a composite radiofrequency (RF) pulse on
saturation recovery (SR) myocardial T1 mapping using a 3T MR system. MATERIALS
AND METHODS: Phantom and in vivo studies were performed with a clinical 3T MR
scanner. Accuracy and reproducibility of the SR T1 mapping using conventional and
composite RF pulses were first compared in phantom experiments. An in vivo study
was performed of 10 healthy volunteers who were imaged with conventional and
composite RF pulse methods twice each. In vivo reproducibility of myocardial T1
value and the inter-segment variability were assessed. RESULTS: The phantom study
revealed significant differences in the mean T1 values between the two methods,
and the reproducibility for the composite RF pulse was significantly smaller than
that for the conventional RF pulse. For both methods, the correlations of the
reference and measured T1 values were excellent (r2 = 0.97 and 0.98 for
conventional and composite RF pulses, respectively). The in vivo study showed
that the mean T1 value for composite RF pulse was slightly lower than that for
conventional RF pulse, but this difference was not significant (P = 0.06). The
inter-segment variability for the composite RF pulse was significantly smaller
than that for conventional RF pulse (P < 0.01). Inter-scan correlations of T1
measurements of the first and second scans were highly and weakly correlated to
composite RF pulses (r = 0.83 and 0.29, respectively). CONCLUSION: SR T1 mapping
using composite RF pulse provides accurate quantification of T1 values and can
lessen measurement variability and enable reproducible T1 measurements.
PMID- 28515410
TI - Differentiating between Central Nervous System Lymphoma and High-grade Glioma
Using Dynamic Susceptibility Contrast and Dynamic Contrast-enhanced MR Imaging
with Histogram Analysis.
AB - PURPOSE: We evaluated the diagnostic performance of histogram analysis of data
from a combination of dynamic susceptibility contrast (DSC)-MRI and dynamic
contrast-enhanced (DCE)-MRI for quantitative differentiation between central
nervous system lymphoma (CNSL) and high-grade glioma (HGG), with the aim of
identifying useful perfusion parameters as objective radiological markers for
differentiating between them. METHODS: Eight lesions with CNSLs and 15 with HGGs
who underwent MRI examination, including DCE and DSC-MRI, were enrolled in our
retrospective study. DSC-MRI provides a corrected cerebral blood volume (cCBV),
and DCE-MRI provides a volume transfer coefficient (Ktrans) for transfer from
plasma to the extravascular extracellular space. Ktrans and cCBV were measured
from a round region-of-interest in the slice of maximum size on the contrast
enhanced lesion. The differences in t values between CNSL and HGG for determining
the most appropriate percentile of Ktrans and cCBV were investigated. The
differences in Ktrans, cCBV, and Ktrans/cCBV between CNSL and HGG were
investigated using histogram analysis. Receiver operating characteristic (ROC)
analysis of Ktrans, cCBV, and Ktrans/cCBV ratio was performed. RESULTS: The 30th
percentile (C30) in Ktrans and 80th percentile (C80) in cCBV were the most
appropriate percentiles for distinguishing between CNSL and HGG from the
differences in t values. CNSL showed significantly lower C80 cCBV, significantly
higher C30 Ktrans, and significantly higher C30 Ktrans/C80 cCBV than those of
HGG. In ROC analysis, C30 Ktrans/C80 cCBV had the best discriminative value for
differentiating between CNSL and HGG as compared to C30 Ktrans or C80 cCBV.
CONCLUSION: The combination of Ktrans by DCE-MRI and cCBV by DSC-MRI was found to
reveal the characteristics of vascularity and permeability of a lesion more
precisely than either Ktrans or cCBV alone. Histogram analysis of these vascular
microenvironments enabled quantitative differentiation between CNSL and HGG.
PMID- 28515411
TI - Evaluating Myometrial Invasion in Endometrial Cancer: Comparison of Reduced Field
of-view Diffusion-weighted Imaging and Dynamic Contrast-enhanced MR Imaging.
AB - PURPOSE: To compare the diagnostic ability of reduced FOV diffusion-weighted (DW)
MR imaging with that of 3D dynamic contrast-enhanced (DCE) MR imaging in
evaluating the depth of myometrial invasion in patients with endometrial cancer.
METHODS: Three tesla MR images including T2-weighted imaging, reduced FOV DW
imaging and 3D DCE MR imaging in sagittal and oblique axial (short axis) planes
in 25 women with surgically proven endometrial cancer were retrospectively
evaluated. The depth of myometrial invasion (stage S: < 50% vs stage D: >= 50%)
on MR imaging was correlated with surgical pathology results. RESULTS: The 25
endometrial cancers included 16 stage S and 9 stage D tumors. The depth of
myometrial invasion could be accurately evaluated in 68% of the cases for T2
weighted imaging, 92% for 3D DCE MR imaging, and 96% for reduced FOV DW imaging.
In two patients with coexisting adenomyosis, both T2-weighted imaging and 3D DCE
MR imaging failed to reveal the deep myometrial invasion, and reduced FOV DW
imaging clearly demonstrated the tumor margin in the cases. Combination of
reduced FOV DW imaging reading together with T2-weighted imaging improved the
assessment of myometrial invasion with a diagnostic accuracy of up to 100%.
CONCLUSIONS: Addition of reduced FOV DW imaging may improve the staging accuracy
of MR imaging for endometrial cancer in assessing the depth of myometrial
invasion. Especially, reduced FOV DW imaging has an advantage in assessing the
depth of myometrial invasion for patients with coexisting adenomyosis. Reduced
FOV DW imaging can be an alternative to 3D DCE MR imaging in evaluating
myometrial invasion of endometrial cancer without the use of contrast medium.
PMID- 28515412
TI - Utility of a Hybrid IVIM-DKI Model to Predict the Development of Distant
Metastasis in Head and Neck Squamous Cell Carcinoma Patients.
AB - PURPOSE: To evaluate the diagnostic power of hybrid intravoxel incoherent motion
(IVIM)-diffusion kurtosis imaging (DKI) model parameters in pretreatment for the
prediction of future distant metastasis in head and neck squamous cell carcinoma
(HNSCC) patients. MATERIALS AND METHODS: We retrospectively evaluated 49 HNSCC
patients who underwent curative chemoradiation therapy. Diffusion-weighted image
(DWI) acquired by single-shot spin-echo echo-planar imaging with 12 b-values (0
2000) was performed in all patients before any treatment. We calculated the IVIM
DKI parameters and the conventional apparent diffusion coefficient (ADC) in the
ROI placed on the primary lesion. The presence of future distant metastasis was
determined by histological findings or clinical follow-up. RESULTS: A univariate
analysis revealed significant differences between the patients with distant
metastasis and those without in slow diffusion coefficient (D) and kurtosis value
(K). Highest diagnostic accuracy was obtained by the D value. In addition, a
multivariate analysis revealed that the D value was an independent predictor of
future distant metastasis. CONCLUSION: The D and K values obtained by this hybrid
IVIM-DKI model can be one of the diagnostic tools for the prediction of future
distant metastasis in HNSCC patients.
PMID- 28515414
TI - Mediastinal Solitary Fibrous Tumor Diagnosed by Endobronchial Ultrasound-Directed
Biopsy.
AB - BACKGROUND Solitary fibrous tumors of the middle mediastinal space are uncommon
and often not discovered until symptoms secondary to compression of adjacent
structures occur. Diagnosis requires surgical biopsy and histological tissue
analysis. We describe the ECHO appearance of the solitary fibrous tumor and
successful non-invasive EBUS diagnosis. This method of diagnosis allowed for
surgical planning for resection and allowed us to exclude non-surgical diseases,
such as small cell carcinoma. CASE REPORT A 32-year-old man presented to his
primary care physician with worsening intermittent chronic chest pain with recent
progressive dysphagia, cough, and dyspnea. Physical examination and routine
laboratory work-up were unrevealing. Chest radiograph and computed tomography
(CT) of the chest revealed a middle mediastinal mass. Flexible bronchoscopy
confirmed extrinsic compression of right and left bronchial trees. Endobronchial
ultrasound (EBUS) was used to biopsy the mass and the diagnosis of solitary
fibrous tumor was confirmed. The patient underwent successful tumor resection and
was discharged home after an uneventful postoperative period. CONCLUSIONS
Endobronchial ultrasound-directed tissue biopsy is an appropriate modality for
suspected solitary fibrous tumors of the mediastinum. To our knowledge, this is
only the second reported case of SFT diagnosed by EBUS-TBNA. Our case uniquely
demonstrates the advantages of pre-surgical diagnosis of mediastinal masses with
EBUS-TBNA when the diagnosis SFT is suggested on CT and US imaging.
PMID- 28515413
TI - Magnetic Susceptibility Changes in the Basal Ganglia and Brain Stem of Patients
with Wilson's Disease: Evaluation with Quantitative Susceptibility Mapping.
AB - OBJECTIVES: Wilson's disease (WD) is characterized with the accumulation of
copper in the liver and brain. The objective of this study is to quantitatively
measure the susceptibility changes of basal ganglia and brain stem of pediatric
patients with neurological WD using quantitative susceptibility mapping (QSM) in
comparison to healthy controls. METHODS: Eleven patients with neurological WD
(mean age 15 +/- 3.3 years, range 10-22 years) and 14 agematched controls were
prospectively recruited. Both groups were scanned on a 1.5 Tesla clinical
scanner. In addition to T1- and T2-weighted MR images, a 3D multi-echo spoiled
gradient echo (GRE) sequence was acquired and QSM images were derived offline.
The quantitative measurement of susceptibility of corpus striatum, thalamus of
each hemisphere, midbrain, and pons were assessed with the region of interest
analysis on the QSM images. The susceptibility values for the patient and control
groups were compared using twosample t-test. RESULTS: One patient with WD had T1
shortening in the bilateral globus pallidus. Another one had hyperintensity in
the bilateral putamen, caudate nuclei, and substantia nigra on T2-weighted
images. The rest of the patients with WD and all subjects of the control group
had no signal abnormalities on conventional MR images. The susceptibility
measures of right side of globus pallidus, putamen, thalamus, midbrain, and
entire pons were significantly different in patients compared to controls (P <
0.05). CONCLUSION: QSM method exhibits increased susceptibility differences of
basal ganglia and brain stem in patients with WD that have neurologic impairment
even if no signal alteration is detected on T1- and T2-weighted MR images.
PMID- 28515416
TI - Observational Evidence for Desert Amplification Using Multiple Satellite
Datasets.
AB - Desert amplification identified in recent studies has large uncertainties due to
data paucity over remote deserts. Here we present observational evidence using
multiple satellite-derived datasets that desert amplification is a real large
scale pattern of warming mode in near surface and low-tropospheric temperatures.
Trend analyses of three long-term temperature products consistently confirm that
near-surface warming is generally strongest over the driest climate regions and
this spatial pattern of warming maximizes near the surface, gradually decays with
height, and disappears in the upper troposphere. Short-term anomaly analyses show
a strong spatial and temporal coupling of changes in temperatures, water vapor
and downward longwave radiation (DLR), indicating that the large increase in DLR
drives primarily near surface warming and is tightly associated with increasing
water vapor over deserts. Atmospheric soundings of temperature and water vapor
anomalies support the results of the long-term temperature trend analysis and
suggest that desert amplification is due to comparable warming and moistening
effects of the troposphere. Likely, desert amplification results from the
strongest water vapor feedbacks near the surface over the driest deserts, where
the air is very sensitive to changes in water vapor and thus efficient in
enhancing the longwave greenhouse effect in a warming climate.
PMID- 28515417
TI - A generalized population dynamics model for reproductive interference with
absolute density dependence.
AB - Interspecific mating interactions, or reproductive interference, can affect
population dynamics, species distribution and abundance. Previous population
dynamics models have assumed that the impact of frequency-dependent reproductive
interference depends on the relative abundances of species. However, this
assumption could be an oversimplification inappropriate for making quantitative
predictions. Therefore, a more general model to forecast population dynamics in
the presence of reproductive interference is required. Here we developed a
population dynamics model to describe the absolute density dependence of
reproductive interference, which appears likely when encounter rate between
individuals is important. Our model (i) can produce diverse shapes of isoclines
depending on parameter values and (ii) predicts weaker reproductive interference
when absolute density is low. These novel characteristics can create conditions
where coexistence is stable and independent from the initial conditions. We
assessed the utility of our model in an empirical study using an experimental
pair of seed beetle species, Callosobruchus maculatus and Callosobruchus
chinensis. Reproductive interference became stronger with increasing total beetle
density even when the frequencies of the two species were kept constant. Our
model described the effects of absolute density and showed a better fit to the
empirical data than the existing model overall.
PMID- 28515415
TI - Evaluation of Mycophenolate Mofetil and Low-Dose Steroid Combined Therapy in
Moderately Severe Henoch-Schonlein Purpura Nephritis.
AB - BACKGROUND The most appropriate management of Henoch-Schonlein Purpura (HSP)
nephritis with nephrotic-range proteinuria remains uncertain. The aim of this
study was to evaluate the clinical therapeutic effects of mycophenolate mofetil
and low-dose steroid in Henoch-Schonlein purpura nephritis (HSPN) with nephrotic
range proteinuria and pathological classification less than IV in children.
MATERIAL AND METHODS The clinical effects of MMF and low-dose steroid therapy
were studied in children with Henoch-Schonlein purpura nephritis manifested with
nephrotic-range proteinuria, normal kidney function, and <50% crescents or
sclerosing lesions on renal biopsy. We enrolled 32 boys and 29 girls with
nephrotic-range proteinuria, normal kidney function, and pathological
classification less than IV on renal biopsy. We treated 41 cases (67.2%) with
mycophenolate mofetil and low-dose prednisone combined therapy and 20 cases
(32.8%) were treated with full-dose prednisone alone. RESULTS Short-term response
was significantly different between 2 groups (chi2=4.371, P=0.037), while no
significant difference was found in long-term prognosis (chi2=0.419, P=0.522)
after follow-up. The ROC curve showed that the most appropriate cutoff value was
30.67 MUg.h/ml for MPA-AUC and the area under the ROC curve was 0.731, with 85.2%
sensitivity and 64.3% specificity. CONCLUSIONS Mycophenolate mofetil and low-dose
prednisone combined therapy is a reasonable treatment choice which can promote
the remission of proteinuria without increasing obvious adverse reactions in
pediatric HSPN with nephrotic state and pathological classification less than
grade IV. MPA-AUC more than 30 MUg.h/ml was an appropriate value for MMF in the
combined therapy with MMF and steroid for treating children with HSPN.
PMID- 28515418
TI - Automatic Segmentation of Kidneys using Deep Learning for Total Kidney Volume
Quantification in Autosomal Dominant Polycystic Kidney Disease.
AB - Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited
disorder of the kidneys. It is characterized by enlargement of the kidneys caused
by progressive development of renal cysts, and thus assessment of total kidney
volume (TKV) is crucial for studying disease progression in ADPKD. However,
automatic segmentation of polycystic kidneys is a challenging task due to severe
alteration in the morphology caused by non-uniform cyst formation and presence of
adjacent liver cysts. In this study, an automated segmentation method based on
deep learning has been proposed for TKV computation on computed tomography (CT)
dataset of ADPKD patients exhibiting mild to moderate or severe renal
insufficiency. The proposed method has been trained (n = 165) and tested (n = 79)
on a wide range of TKV (321.2-14,670.7 mL) achieving an overall mean Dice
Similarity Coefficient of 0.86 +/- 0.07 (mean +/- SD) between automated and
manual segmentations from clinical experts and a mean correlation coefficient
(rho) of 0.98 (p < 0.001) for segmented kidney volume measurements in the entire
test set. Our method facilitates fast and reproducible measurements of kidney
volumes in agreement with manual segmentations from clinical experts.
PMID- 28515419
TI - New insights into ocean sunfish (Mola mola) abundance and seasonal distribution
in the northeast Atlantic.
AB - The ocean sunfish, Mola mola, is the largest teleost fish in the world. Despite
being found in all oceans of the world, little is known about its abundance and
factors driving its distribution. In this study we provide the first abundance
estimates for sunfish in offshore waters in the northeast Atlantic and the first
record of extensive sunfish presence in these waters year-round. Abundance
estimates and predictive distributions for sunfish in approximately 300,000 km2
of the northeast Atlantic were derived from large scale offshore aerial surveys
in 2015-2016 using distance sampling techniques. Generalized additive models of
sunfish density were fitted to survey data from 17,360 km of line transect effort
resulting in minimum abundance estimates of 12,702 (CI: 9,864-16,357) in the
summer (Density = 0.043 ind/km2) and 8,223 individuals (CI: 6,178-10,946)
(Density = 0.028 ind/km2) in the winter. Density surface models predicted
seasonal shifts in distribution and highlighted the importance of the mixed layer
depth, possibly related to thermoregulation following deep foraging dives. The
abundance estimate and estimated daily consumption of 2,600 tonnes of jellyfish
in the northeast Atlantic highlights the need to re-assess the importance of this
species in the pelagic ecosystem, and its role in top-down control of jellyfish
blooms.
PMID- 28515420
TI - Vascular Remodelling Relates to an Elevated Oscillatory Shear Index and Relative
Residence Time in Spontaneously Hypertensive Rats.
AB - Haemodynamic disorders are common clinical findings in hypertension and lead to
adverse cardiovascular events. However, the haemodynamic conditions in
hypertension models are poorly understood. This study aimed to observe the
characteristics of haemodynamics in spontaneously hypertensive rats (SHRs) and
antihypertensive-treated SHRs. Twenty-four adult male SHRs and Wistar-Kyoto rats
(WKYs) were randomly divided into four groups and treated for 7 days as follows:
WKY-CON (WKYs + saline), WKY-NIF (WKYs + nifedipine, 50 mg/kg/day), SHR-CON (SHRs
+ saline), and SHR-NIF (SHRs + nifedipine). Aortic computational fluid dynamics
(CFD) models were simulated to obtain the haemodynamic parameters. We found that
in the hypertensive (SHR-CON) and blood pressure-controlled (SHR-NIF) groups, the
oscillatory shear index (OSI) and relative residence time (RRT), which are key
haemodynamics indices, were markedly elevated. Furthermore, there was a
correlation between both the elevated OSI and RRT with the vascular wall
thickening in regions near the inner wall of the aortic arch. Our research
demonstrates that haemodynamics remains disturbed even if the blood pressure is
normalized. In addition, vascular remodelling may play an important role in
maintaining elevated OSI and RRT values.
PMID- 28515421
TI - Comparative transcriptome analysis of Rimicaris sp. reveals novel molecular
features associated with survival in deep-sea hydrothermal vent.
AB - Shrimp of the family Alvinocarididae are the predominant megafauna of deep-sea
hydrothermal vents. However, genome information on this family is currently
unavailable. In the present study, by employing Illumina sequencing, we performed
the first de novo transcriptome analysis of the gills of the shrimp Rimicaris sp.
from the hydrothermal vent in Desmos, Manus Basin. The analysis was conducted in
a comparative manner with the shrimp taken directly from the vent (GR samples)
and the shrimp that had been maintained for ten days under normal laboratory
condition (mGR samples). Among the 128,938 unigenes identified, a large number of
differentially expressed genes (DEGs) between the GR and mGR samples were
detected, including 2365 and 1607 genes significantly upregulated and
downregulated, respectively, in GR. The DEGs covered diverse functional
categories. Most of the DEGs associated with immunity were downregulated in GR,
while most of the DEGs associated with sulfur metabolism and detoxification were
upregulated in GR. These results provide the first comprehensive transcriptomic
resource for hydrothermal vent Rimicaris and revealed varied categories of genes
likely involved in deep-sea survival.
PMID- 28515422
TI - Up regulation and nuclear translocation of Y-box binding protein 1 (YB-1) is
linked to poor prognosis in ERG-negative prostate cancer.
AB - Y-box binding protein 1 (YB-1) is an RNA and DNA binding factor with potential
prognostic cancer. To evaluate the clinical impact of YB-1, a tissue microarray
with 11,152 prostate cancers was analysed by immunohistochemistry. Cytoplasmic
and nuclear staining was separately analysed. Cytoplasmic YB-1 was absent or weak
in normal epithelium but seen in 86,3% of carcinomas. Cytoplasmic staining was
weak, moderate, and strong in 29.6%, 43.7% and 13.0% of tumours and was
accompanied by nuclear YB-1 staining in 32.1% of cases. Particularly nuclear
staining was strongly linked to poor patient prognosis (p < 0.0001). YB-1 protein
was more abundant in ERG positive (95.1%) than in ERG negative cancers (80.4%; p
< 0.0001), but any prognostic impact of YB-1 staining was limited to the ERG
negative subset. Similarly, significant associations with pT stage and Gleason
grade (p < 0.0001 each) were driven by the ERG negative subset. The significant
association of YB-1 protein detection with deletions of PTEN, 5q21 and 6q15 fits
well in the protein's role as an inhibitor of DNA damage dependent cell cycle
arrest, a role that is likely to induce genomic instability. In summary, the data
show, that the prognostic impact of YB-1 expression is limited to ERG negative
prostate cancers.
PMID- 28515423
TI - MiR-520b as a novel molecular target for suppressing stemness phenotype of head
neck cancer by inhibiting CD44.
AB - Cancer stem cells preferentially acquire the specific characteristics of stress
tolerance and high mobility, allowing them to progress to a therapy-refractive
state. To identify a critical molecule to regulate cancer stemness is
indispensable to erratically cure cancer. In this study, we identified miR-520b
as a novel molecular target to suppress head-neck cancer (HNC) with stemness
phenotype. MiR-520b inhibited cellular migration and invasion via the mechanism
of epithelial-mesenchymal transition. It also sensitized cells to therapeutic
drug and irradiation. Significantly, miR-520b suppressed spheroid cell formation,
as well as reduced expressions of multiple stemness regulators (Nestin, Twist,
Nanog, Oct4). The CD44 molecule was identified as a direct target of miR-520b, as
shown by the reverse correlative expressions, the response to miR-520 modulation,
the luciferase reporter assay, and the functional rescue analyses. These cellular
results were confirmed by a tumor xenograft mice study. Administration of miR
520b dramatically restrained tumorigenesis and liver colonization. Conversely,
miR-520b silencing led to an acceleration of tumor growth. Taken together, our
study demonstrated that miR-520b inhibits the malignancy of HNC through
regulation of cancer stemness conversion by targeting CD44. MiR-520b may serve as
an emerging therapeutic target that may be further developed for the intervention
of refractory HNC.
PMID- 28515424
TI - A Split Ring Resonator Dielectric Probe for Near-Field Dielectric Imaging.
AB - A single split-ring resonator (SRR) probe for 2D surface mapping and imaging of
relative dielectric permittivity for the characterisation of composite materials
has been developed. The imaging principle, the analysis and the sensitivity of
the SRR surface dielectric probe data is described. The surface dielectric
properties of composite materials in the frequency range 1-3 GHz have been
measured based on the magnetic resonance frequency of the transmission loss of
the SRR dielectric probe when in contact with the surface. The SRR probe
performance was analysed analytically and using full-wave simulation, and
predictions showed close agreement with experiment for composite materials with
spatially varying dielectric permittivity manufactured by 3D printing. The
spatial and permittivity resolution of the SRR dielectric probe were controlled
by the geometrical parameters of the SRR which provided flexibility to tune the
SRR probe. The best accuracy of the dielectric permittivity measurements was
within 5%.
PMID- 28515425
TI - New Insight into the Ground State of FePc: A Diffusion Monte Carlo Study.
AB - We have applied DMC to evaluate relative stability of the possible electronic
configurations of an isolated FePc under D 4h symmetry, considering some fixed
nodes generated from different methods. They predict A 2g ground state
consistently, supporting preceding DFT studies, with confidence overcoming the
ambiguity about exchange-correlation (XC) functionals. By comparing DMC with
several XC, we clarified the importance of the short-range exchange to describe
the relative stability. We examined why the predicted A 2g is excluded from
possible ground states in the recent ligand field based model. Simplified
assumptions made in the superposition model are identified to give unreasonably
less energy gain for A 2g when compared with the reality. The state is found to
have possible reasons for the stabilization, reducing the occupations from an
unstable anti-bonding orbital, avoiding double occupation of a spatially
localized orbital, and gaining exchange energy by putting a triplet spin pair in
degenerate orbitals.
PMID- 28515428
TI - Cell morphology governs directional control in swimming bacteria.
AB - The ability to rapidly detect and track nutrient gradients is key to the
ecological success of motile bacteria in aquatic systems. Consequently, bacteria
have evolved a number of chemotactic strategies that consist of sequences of
straight runs and reorientations. Theoretically, both phases are affected by
fluid drag and Brownian motion, which are themselves governed by cell geometry.
Here, we experimentally explore the effect of cell length on control of swimming
direction. We subjected Escherichia coli to an antibiotic to obtain motile cells
of different lengths, and characterized their swimming patterns in a homogeneous
medium. As cells elongated, angles between runs became smaller, forcing a change
from a run-and-tumble to a run-and-stop/reverse pattern. Our results show that
changes in the motility pattern of microorganisms can be induced by simple
morphological variation, and raise the possibility that changes in swimming
pattern may be triggered by both morphological plasticity and selection on
morphology.
PMID- 28515426
TI - Tolerability of Opioid Analgesia for Chronic Pain: A Network Meta-Analysis.
AB - Aim of this study was to study the tolerability of opioid analgesia by performing
a network meta-analysis (NMA) of randomized-controlled trials (RCTs) which
investigated effectiveness of opioids for the management of chronic pain.
Research articles reporting outcomes of RCT/s comparing 2 or more opioid
analgesics for the management of chronic pain were obtained by database search.
Bayesian NMAs were performed to combine direct comparisons between treatments
with that of indirect simulated evidence. Study endpoints were: incidence of
adverse events, incidence of constipation, trial withdrawal rate, and patient
satisfaction with treatment. Outcomes were also compared with conventional meta
analyses. Thirty-two studies investigating 10 opioid drugs fulfilled the
eligibility criteria. Tapentadol treatment was top-ranking owing to lower
incidence of overall adverse events, constipation, and least trial withdrawal
rate. Tapentadol was followed by oxycodone-naloxone combination in providing
better tolerability and less trial withdrawal rate. Patient satisfaction was
found to be higher with oxycodone-naloxone followed by fentanyl and tapentadol.
These results were in agreement with those achieved with conventional meta
analyses. Tapentadol and oxycodone-naloxone are found to exhibit better
tolerability characteristics in comparison with other opioid drugs for the
management of chronic pain and are associated with low trial withdrawal rate and
better patient satisfaction.
PMID- 28515427
TI - Pediatric vision screening using the plusoptiX A12C photoscreener in Chinese
preschool children aged 3 to 4 years.
AB - This study evaluated the performance of plusoptiX A12C in detecting amblyopia
risk factors (ARFs) in Chinese children aged 3-to-4-year. PlusoptiX examination
was successfully conducted among 1,766 subjects without cycloplegia to detect
refractive error, asymmetry and media opacity. Cycloplegic retinoscopy (CR) was
conducted on 357 children suspected of having vision abnormalities. Statistical
differences between CR and the device were confirmed using the mean spherical
value (+1.41 +/- 0.87 D versus +1.14 +/- 0.81 D), cylindrical value (-0.47 +/-
0.64 versus -0.84 +/- 0.78) and spherical equivalent (SE) value (+1.17 +/- 0.84 D
versus +0.72 +/- 0.64 D) (all P < 0.0001). In the emmetropia group, the
differences were statistically significant for the cylinder and SE (all P <
0.0001) but not the sphere (P = 0.33). In the hyperopia group, the differences
were statistically significant for the sphere, cylinder and SE (all P < 0.0001).
For refractive and strabismic ARFs detection, the sensitivity, specificity,
positive predictive value, and negative predictive value were calculated,
respectively.
PMID- 28515429
TI - Endocytic uptake of monomeric amyloid-beta peptides is clathrin- and dynamin
independent and results in selective accumulation of Abeta(1-42) compared to
Abeta(1-40).
AB - Intraneuronal accumulation of amyloid-beta (Abeta) peptides represent an early
pathological feature in Alzheimer's disease. We have therefore utilized flow
cytometry and confocal microscopy in combination with endocytosis inhibition to
explore the internalisation efficiency and uptake mechanisms of Abeta(1-40) and
Abeta(1-42) monomers in cultured SH-SY5Y cells. We find that both variants are
constitutively internalised via endocytosis and that their uptake is proportional
to cellular endocytic rate. Moreover, SH-SY5Y cells internalise consistently
twice the amount of Abeta(1-42) compared to Abeta(1-40); an imaging-based
quantification showed that cells treated with 1 uM peptide for 8 h contained
800,000 peptides of Abeta(1-42) and 400,000 of Abeta(1-40). Both variants co
localised to >90% with lysosomes or other acidic compartments. Dynasore and
chlorpromazine endocytosis inhibitors were both found to reduce uptake,
particularly of Abeta(1-42). Overexpression of the C-terminal of the clathrin
binding domain of AP180, dynamin2 K44A, or Arf6 Q67L did however not reduce
uptake of the Abeta variants. By contrast, perturbation of actin polymerisation
and inhibition of macropinocytosis reduced Abeta(1-40) and Abeta(1-42) uptake
considerably. This study clarifies mechanisms of Abeta(1-40) and Abeta(1-42)
uptake, pinpoints differences between the two variants and highlights a common
and putative role of macropinocytosis in the early accumulation of intraneuronal
Abeta in AD.
PMID- 28515430
TI - A microfluidic chip for screening individual cancer cells via eavesdropping on
autophagy-inducing crosstalk in the stroma niche.
AB - Autophagy is a cellular homeostatic mechanism where proteins and organelles are
digested and recycled to provide an alternative source of building blocks and
energy to cells. The role of autophagy in cancer microenvironment is still poorly
understood. Here, we present a microfluidic system allowing monitoring of the
crosstalk between single cells. We used this system to study how tumor cells
induced autophagy in the stromal niche. Firstly, we could confirm that
transforming growth factor beta1 (TGFbeta1) secreted from breast tumor cells is a
paracrine mediator of tumor-stroma interaction leading to the activation of
autophagy in the stroma component fibroblasts. Through proof of concept
experiments using TGFbeta1 as a model factor, we could demonstrate real time
monitoring of autophagy induction in fibroblasts by single tumor cells. Retrieval
of individual tumor cells from the microfluidic system and their subsequent
genomic analysis was possible, allowing us to determine the nature of the factor
mediating tumor-stroma interactions. Therefore, our microfluidic platform might
be used as a promising tool for quantitative investigation of tumor-stroma
interactions, especially for and high-throughput screening of paracrine factors
that are secreted from heterogeneous tumor cell populations.
PMID- 28515431
TI - Early Onset of Nucleate Boiling on Gas-covered Biphilic Surfaces.
AB - For phase-change cooling schemes for electronics, quick activation of nucleate
boiling helps safeguard the electronics components from thermal shocks associated
with undesired surface superheating at boiling incipience, which is of great
importance to the long-term system stability and reliability. Previous
experimental studies show that bubble nucleation can occur surprisingly early on
mixed-wettability surfaces. In this paper, we report unambiguous evidence that
such unusual bubble generation at extremely low temperatures-even below the
boiling point-is induced by a significant presence of incondensable gas retained
by the hydrophobic surface, which exhibits exceptional stability even surviving
extensive boiling deaeration. By means of high-speed imaging, it is revealed that
the consequently gassy boiling leads to unique bubble behaviour that stands in
sharp contrast with that of pure vapour bubbles. Such findings agree
qualitatively well with numerical simulations based on a diffuse-interface
method. Moreover, the simulations further demonstrate strong thermocapillary
flows accompanying growing bubbles with considerable gas contents, which is
associated with heat transfer enhancement on the biphilic surface in the low
superheat region.
PMID- 28515432
TI - High-salt intake negatively regulates fat deposition in mouse.
AB - High-salt (HS) intake contributes to hypertension and cardiopathy, but the effect
of HS on fat deposition is controversial. Feed intake, fat mass, the percentage
of abdominal fat, heat production, rate of oxygen consumption and the respiratory
exchange ratio of mice on a HS diet were significantly decreased (P < 0.01 or
0.05) compared with mice on a normal-salt (NS) diet. An in vitro experiment with
differentiating pre-adipocytes showed reduced fat deposition in the presence of
high concentrations of NaCl (>0.05 M). Abdominal fat mRNA profiles and protein
measurements showed that 5 known genes involved in lipolysis were up-regulated
significantly and 9 genes related to lipogenesis were down-regulated in HS mice.
Abundant genes and some proteins (ATP2a1, AGT, and ANGPTL4) related to calcium
ion metabolism or the renin-angiotensin system (RAS) were differentially
expressed between HS and NS mice. Of special interest, CREB1 phosphorylation
(S133 and S142), a key factor involved in calcium signaling and other pathways,
was up-regulated in HS mice. By IPA analysis, a network mediated by calcium was
established providing the molecular mechanisms underlying the negative effect of
HS on fat deposition.
PMID- 28515435
TI - Genetic diversity of armored scales (Hemiptera: Diaspididae) and soft scales
(Hemiptera: Coccidae) in Chile.
AB - Scale insects (Sternorrhyncha: Coccoidea) are one of the most invasive and
agriculturally damaging insect groups. Their management and the development of
new control methods are currently jeopardized by the scarcity of identification
data, in particular in regions where no large survey coupling morphological and
DNA analyses have been performed. In this study, we sampled 116 populations of
armored scales (Hemiptera: Diaspididae) and 112 populations of soft scales
(Hemiptera: Coccidae) in Chile, over a latitudinal gradient ranging from 18
degrees S to 41 degrees S, on fruit crops, ornamental plants and trees. We
sequenced the COI and 28S genes in each population. In total, 19 Diaspididae
species and 11 Coccidae species were identified morphologically. From the 63 COI
haplotypes and the 54 28S haplotypes uncovered, and using several DNA data
analysis methods (Automatic Barcode Gap Discovery, K2P distance, NJ trees), up to
36 genetic clusters were detected. Morphological and DNA data were congruent,
except for three species (Aspidiotus nerii, Hemiberlesia rapax and Coccus
hesperidum) in which DNA data revealed highly differentiated lineages. More than
50% of the haplotypes obtained had no high-scoring matches with any of the
sequences in the GenBank database. This study provides 63 COI and 54 28S barcode
sequences for the identification of Coccoidea from Chile.
PMID- 28515433
TI - The sleep-deprived human brain.
AB - How does a lack of sleep affect our brains? In contrast to the benefits of sleep,
frameworks exploring the impact of sleep loss are relatively lacking.
Importantly, the effects of sleep deprivation (SD) do not simply reflect the
absence of sleep and the benefits attributed to it; rather, they reflect the
consequences of several additional factors, including extended wakefulness. With
a focus on neuroimaging studies, we review the consequences of SD on attention
and working memory, positive and negative emotion, and hippocampal learning. We
explore how this evidence informs our mechanistic understanding of the known
changes in cognition and emotion associated with SD, and the insights it provides
regarding clinical conditions associated with sleep disruption.
PMID- 28515436
TI - Nimbolide upregulates RECK by targeting miR-21 and HIF-1alpha in cell lines and
in a hamster oral carcinogenesis model.
AB - Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a potent
inhibitor of matrix metalloproteinases (MMPs) is a common negative target of
oncogenic signals and a potential therapeutic target for novel drug development.
Here, we show that sequential RECKlessness stimulates angiogenesis and Notch
signalling in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal
pouch (HBP) carcinogenesis model, a paradigm for oral oncogenesis and
chemointervention. We also report the chemotherapeutic effect of nimbolide, a
limonoid from the neem tree (Azadirachta indica) based on the upregulation of
RECK as well as modulation of the expression of key molecules involved in
invasion and angiogenesis. We demonstrate that nimbolide upregulates RECK by
targeting miR-21, and HIF-1alpha resulting in reduced MMP activity and blockade
of VEGF and Notch signalling. Nimbolide reduced microvascular density, confirming
its anti-angiogenic potential. Molecular docking analysis revealed interaction of
nimbolide with HIF-1alpha. Additionally, we demonstrate that nimbolide
upregulates RECK expression via downregulation of HIF-1alpha and miR-21 by
overexpression and knockdown experiments in SCC4 and EAhy926 cell lines. Taken
together, these findings provide compelling evidence that targeting RECK, a
keystone protein that regulates mediators of invasion and angiogenesis with
phytochemicals such as nimbolide may be a robust therapeutic approach to prevent
oral cancer progression.
PMID- 28515437
TI - CoCO3 from one-step micro-emulsion method as electrode materials for Faradaic
capacitors.
AB - Faradaic capacitor (FC) has been widely investigated during the past few decades,
and dozens of prototypes have been proposed. However, it has not reached its full
potential. In this work, we demonstrate a kind of FC comprising of a CoCO3
electrode. Synthesized through a micro-emulsion route, such CoCO3 shows low
crystallinity and porous wool-ball structures stacked by needle-like individuals.
It shows desirable electrochemical properties in terms of excellent high-rate
performance and high reversibility. Also, it could deliver a capacitance of 440
F.g-1 at 1 A.g-1, and shows no capacitance decay after 1000 cycles. Since metal
carbonate is capable of delivering good electrochemical performances and its
preparation is easier and more cost-efficient, it should be a feasible candidate
for electrode material of FC.
PMID- 28515434
TI - Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer
disease.
AB - Cerebral blood flow (CBF) regulation is essential for normal brain function. The
mammalian brain has evolved a unique mechanism for CBF control known as
neurovascular coupling. This mechanism ensures a rapid increase in the rate of
CBF and oxygen delivery to activated brain structures. The neurovascular unit is
composed of astrocytes, mural vascular smooth muscle cells and pericytes, and
endothelia, and regulates neurovascular coupling. This Review article examines
the cellular and molecular mechanisms within the neurovascular unit that
contribute to CBF control, and neurovascular dysfunction in neurodegenerative
disorders such as Alzheimer disease.
PMID- 28515438
TI - Mitochondrial retrograde signaling connects respiratory capacity to thermogenic
gene expression.
AB - Mitochondrial respiration plays a crucial role in determining the metabolic state
of brown adipose tissue (BAT), due to its direct roles in thermogenesis, as well
as through additional mechanisms. Here, we show that respiration-dependent
retrograde signaling from mitochondria to nucleus contributes to genetic and
metabolic reprogramming of BAT. In mouse BAT, ablation of LRPPRC (LRP130), a
potent regulator of mitochondrial transcription and respiratory capacity,
triggers down-regulation of thermogenic genes, promoting a storage phenotype in
BAT. This retrograde regulation functions by inhibiting the recruitment of
PPARgamma to the regulatory elements of thermogenic genes. Reducing cytosolic
Ca2+ reverses the attenuation of thermogenic genes in brown adipocytes with
impaired respiratory capacity, while induction of cytosolic Ca2+ is sufficient to
attenuate thermogenic gene expression, indicating that cytosolic Ca2+ mediates
mitochondria-nucleus crosstalk. Our findings suggest respiratory capacity governs
thermogenic gene expression and BAT function via mitochondria-nucleus
communication, which in turn leads to either a thermogenic or storage mode.
PMID- 28515439
TI - The Biomechanics Behind Extreme Osteophagy in Tyrannosaurus rex.
AB - Most carnivorous mammals can pulverize skeletal elements by generating tooth
pressures between occluding teeth that exceed cortical bone shear strength,
thereby permitting access to marrow and phosphatic salts. Conversely, carnivorous
reptiles have non-occluding dentitions that engender negligible bone damage
during feeding. As a result, most reptilian predators can only consume bones in
their entirety. Nevertheless, North American tyrannosaurids, including the giant
(13 metres [m]) theropod dinosaur Tyrannosaurus rex stand out for habitually
biting deeply into bones, pulverizing and digesting them. How this mammal-like
capacity was possible, absent dental occlusion, is unknown. Here we analyzed T.
rex feeding behaviour from trace evidence, estimated bite forces and tooth
pressures, and studied tooth-bone contacts to provide the answer. We show that
bone pulverization was made possible through a combination of: (1) prodigious
bite forces (8,526-34,522 newtons [N]) and tooth pressures (718-2,974 megapascals
[MPa]) promoting crack propagation in bones, (2) tooth form and dental arcade
configurations that concentrated shear stresses, and (3) repetitive, localized
biting. Collectively, these capacities and behaviors allowed T. rex to finely
fragment bones and more fully exploit large dinosaur carcasses for sustenance
relative to competing carnivores.
PMID- 28515441
TI - Fluorescence dynamics of the biosynthesized CdSe quantum dots in Candida utilis.
AB - Organisms served as factories of bio-assembly of nanoparticles attracted a lot of
attentions due to the safe, economic and environmental-benignity traits,
especially the fabrication of the super fluorescence properties quantum dots
(QDs). However, information about the developmental dynamics of QDs in living
organisms is still lacking. In this work, we synthesized cadmium-selenium (CdSe)
QDs in Candida utilis WSH02-08, and then tracked and quantitatively characterized
the developmental dynamics (photoactivation, photostable and photobleaching
processes) of bio-QDs by translating fluorescence microscopy movies into visual
quantitative curve. These findings shed light on the fluorescence properties of
the bio-assembled QDs and are expected to accelerate the applications of the
synthesized QDs in vivo. It provided a new way to screen bio-QDs and monitor the
quality of QDs in vivo.
PMID- 28515442
TI - Interplay between Alternative Splicing and Alternative Polyadenylation Defines
the Expression Outcome of the Plant Unique OXIDATIVE TOLERANT-6 Gene.
AB - Pre-mRNA alternative splicing and alternative polyadenylation have been
implicated to play important roles during eukaryotic gene expression. However,
much remains unknown regarding the regulatory mechanisms and the interactions of
these two processes in plants. Here we focus on an Arabidopsis gene OXT6
(Oxidative Tolerant-6) that has been demonstrated to encode two proteins through
alternative splicing and alternative polyadenylation. Specifically, alternative
polyadenylation at Intron-2 of OXT6 produces a transcript coding for AtCPSF30, an
Arabidopsis ortholog of 30 kDa subunit of the Cleavage and Polyadenylation
Specificity Factor. On the other hand, alternative splicing of Intron-2 generates
a longer transcript encoding a protein named AtC30Y, a polypeptide including most
part of AtCPSF30 and a YT521B domain. To investigate the expression outcome of
OXT6 in plants, a set of mutations were constructed to alter the splicing and
polyadenylation patterns of OXT6. Analysis of transgenic plants bearing these
mutations by quantitative RT-PCR revealed a competition relationship between
these two processes. Moreover, when both splice sites and poly(A) signals were
mutated, polyadenylation became the preferred mode of OXT6 processing. These
results demonstrate the interplay between alternative splicing and alternative
polyadenylation, and it is their concerted actions that define a gene's
expression outcome.
PMID- 28515440
TI - A Highly Potent Class of Halogenated Phenazine Antibacterial and Biofilm
Eradicating Agents Accessed Through a Modular Wohl-Aue Synthesis.
AB - Unlike individual, free-floating planktonic bacteria, biofilms are surface
attached communities of slow- or non-replicating bacteria encased within a
protective extracellular polymeric matrix enabling persistent bacterial
populations to tolerate high concentrations of antimicrobials. Our current
antibacterial arsenal is composed of growth-inhibiting agents that target rapidly
dividing planktonic bacteria but not metabolically dormant biofilm cells. We
report the first modular synthesis of a library of 20 halogenated phenazines
(HP), utilizing the Wohl-Aue reaction, that targets both planktonic and biofilm
cells. New HPs, including 6-substituted analogues, demonstrate potent
antibacterial activities against MRSA, MRSE and VRE (MIC = 0.003-0.78 uM). HPs
bind metal(II) cations and demonstrate interesting activity profiles when co
treated in a panel of metal(II) cations in MIC assays. HP 1 inhibited RNA and
protein biosynthesis while not inhibiting DNA biosynthesis using 3H-radiolabeled
precursors in macromolecular synthesis inhibition assays against MRSA. New HPs
reported here demonstrate potent eradication activities (MBEC = 0.59-9.38 uM)
against MRSA, MRSE and VRE biofilms while showing minimal red blood cell lysis or
cytotoxicity against HeLa cells. PEG-carbonate HPs 24 and 25 were found to have
potent antibacterial activities with significantly improved water solubility. HP
small molecules could have a dramatic impact on persistent, biofilm-associated
bacterial infection treatments.
PMID- 28515443
TI - Development of a Whole Organism Platform for Phenotype-Based Analysis of IGF1R
PI3K-Akt-Tor Action.
AB - Aberrant regulation of the insulin-like growth factor (IGF)/insulin (IIS)-PI3K
AKT-TOR signaling pathway is linked to major human diseases, and key components
of this pathway are targets for therapeutic intervention. Current assays are
molecular target- or cell culture-based platforms. Due to the great in vivo
complexities inherited in this pathway, there is an unmet need for whole organism
based assays. Here we report the development of a zebrafish transgenic line,
Tg(igfbp5a:GFP), which faithfully reports the mitotic action of IGF1R-PI3K-Akt
Tor signaling in epithelial cells in real-time. This platform is well suited for
high-throughput assays and real-time cell cycle analysis. Using this platform,
the dynamics of epithelial cell proliferation in response to low [Ca2+] stress
and the distinct roles of Torc1 and Torc2 were elucidated. The availability of
Tg(igfbp5a:GFP) line provides a whole organism platform for phenotype-based
discovery of novel players and inhibitors in the IIS-PI3K-Akt-Tor signaling
pathway.
PMID- 28515444
TI - Orbital angular momentum analysis for giant spin splitting in solids and
nanostructures.
AB - Giant spin splitting (GSS) of electronic bands, which is several orders of
magnitude greater than the standard Rashba effect has been observed in various
systems including noble-metal surfaces and thin films of transition-metal
dichalcogenides. Previous studies reported that orbital angular momentum (OAM) is
not quenched in some GSS materials and that the atomic spin-orbit interaction
(SOI) generates spin splitting in some solid states via the interorbital hopping.
Although the unquenched OAM may be closely related to the interorbital hopping,
their relationship is hardly studied in the aspect of using the unquenched OAM as
a control parameter of GSS. Here, we analyze OAM in GSS materials by using the
interorbital-hopping mechanism and first-principles calculations. We report that
the interatomic hopping between different-parity orbitals, which is generated by
specific broken mirror symmetry, produces k-dependent OAM, resulting in valley
dependent GSS in WSe2 monolayer, Rashba-type GSS in Au (111) surface, and
Dresselhaus-type GSS in bulk HgTe. We also demonstrate systematic control of OAM
by pressure, external fields, and substrates, thereby controlling the spin
splitting, and discuss the temperature dependence of OAM. Our results provide a
simplified picture for systematic design and control of GSS materials.
PMID- 28515445
TI - Protein kinase C inhibitor chelerythrine selectively inhibits proliferation of
triple-negative breast cancer cells.
AB - Triple-negative breast cancer (TNBC) is a subtype of breast cancer lacking
targeted therapy currently. Recent studies imply that protein kinase C may play
important roles in TNBC development and could be a specific target. In this
study, we evaluated the anti-proliferative activity of PKC inhibitor
chelerythrine on a panel of breast cancer cell lines. Chelerythrine selectively
inhibited the growth of TNBC cell lines compared to non-TNBC cell lines as
demonstrated by in vitro cell proliferation assay and colony formation assay, as
well as evidenced by in vivo xenograft assay. The selective anti-proliferative
effect of chelerythrine was associated with induction of apoptosis in TNBC cell
lines. We further demonstrated that PKN2, one of the PKC subtypes, was highly
expressed in TNBC cell lines, and knocking down PKN2 in TNBC cells inhibited
colony formation and xenograft growth. This indicates that PKN2 is required for
the survival of TNBC cells, and could be the target mediates the selective
activity of chelerythrine. Finally, combination of chelerythrine and chemotherapy
reagent taxol showed synergistic/additive effect on TNBC cell lines. Our results
suggest chelerythrine or other PKC inhibitors may be promising regimens for TNBC
tumors.
PMID- 28515446
TI - Phase-channel dynamics reveal the role of impurities and screening in a quasi-one
dimensional charge-density wave system.
AB - Charge density waves (CDWs), i.e. the periodic spatial modulation of coupled
electronic and lattice density, are ubiquitous in low-dimensional conductors and
have taken on renewed relevance due their role in state-of-the-art materials,
e.g. high-T c superconductors, topological insulators and low-dimensional carbon.
As CDWs are described by a complex order parameter to represent both the
amplitude and phase, they are formally analogous to BCS superconductors and spin
waves, providing a prototype of collective phenomena for the further development
of field theories and ab-initio calculations of complex solids. The low-energy
excitations are mixed electron-phonon quanta which ideally separate into an
amplitude and phase channel, and provide a sensitive probe of the ground state
and non-equilibrium dynamics, including ultrafast photoinduced phase transitions.
While recent studies of the amplitude modes have brought substantial progress
aided by a phenomenological Ginzburg-Landau framework, we focus here on the phase
modes using ultrafast terahertz spectroscopy. Experiments on K0.3MoO3 provide a
more complete picture, and reveal a high sensitivity to interactions with
impurities and screening effects from photogenerated carriers, both of which can
be accounted for by generalizations of the model. Moreover, our considerations
emphasize the need to revisit the treatment of inherent electronic damping in
quantum-mechanical CDW theories.
PMID- 28515447
TI - DLX3 interacts with GCM1 and inhibits its transactivation-stimulating activity in
a homeodomain-dependent manner in human trophoblast-derived cells.
AB - The placental transcription factors Distal-less 3 (DLX3) and Glial cell missing-1
(GCM1) have been shown to coordinate the specific regulation of PGF in human
trophoblast cell lines. While both factors independently have a positive effect
on PGF gene expression, when combined, DLX3 acts as an antagonist to GCM. Despite
this understanding, potential mechanisms accounting for this regulatory
interaction remain unexplored. We identify physical and functional interactions
between specific domains of DLX3 and GCM1 in human trophoblast-derived cells by
performing immunoprecipitation and mammalian one hybrid assays. Studies revealed
that DLX3 binding reduced the transcriptional activity of GCM1, providing a
mechanistic explanation of their functional antagonism in regulating PGF promoter
activity. The DLX3 homeodomain (HD) was essential for DLX3-GCM1 interaction, and
that the HD together with the DLX3 amino- or carboxyl-terminal domains was
required for maximal inhibition of GCM1. Interestingly, a naturally occurring
DLX3 mutant that disrupts the carboxyl-terminal domain leading to tricho-dento
osseous syndrome in humans displayed activities indistinguishable from wild type
DLX3 in this system. Collectively, our studies demonstrate that DLX3 physically
interacts with GCM1 and inhibits its transactivation activity, suggesting that
DLX3 and GCM1 may form a complex to functionally regulate placental cell function
through modulation of target gene expression.
PMID- 28515448
TI - Involvement Of Vascular Aldosterone Synthase In Phosphate-Induced Osteogenic
Transformation Of Vascular Smooth Muscle Cells.
AB - Vascular calcification resulting from hyperphosphatemia is a major determinant of
mortality in chronic kidney disease (CKD). Vascular calcification is driven by
aldosterone-sensitive osteogenic transformation of vascular smooth muscle cells
(VSMCs). We show that even in absence of exogenous aldosterone, silencing and
pharmacological inhibition (spironolactone, eplerenone) of the mineralocorticoid
receptor (MR) ameliorated phosphate-induced osteo-/chondrogenic transformation of
primary human aortic smooth muscle cells (HAoSMCs). High phosphate concentrations
up-regulated aldosterone synthase (CYP11B2) expression in HAoSMCs. Silencing and
deficiency of CYP11B2 in VSMCs ameliorated phosphate-induced osteogenic
reprogramming and calcification. Phosphate treatment was followed by nuclear
export of APEX1, a CYP11B2 transcriptional repressor. APEX1 silencing up
regulated CYP11B2 expression and stimulated osteo-/chondrogenic transformation.
APEX1 overexpression blunted the phosphate-induced osteo-/chondrogenic
transformation and calcification of HAoSMCs. Cyp11b2 expression was higher in
aortic tissue of hyperphosphatemic klotho-hypomorphic (kl/kl) mice than in wild
type mice. In adrenalectomized kl/kl mice, spironolactone treatment still
significantly ameliorated aortic osteoinductive reprogramming. Our findings
suggest that VSMCs express aldosterone synthase, which is up-regulated by
phosphate-induced disruption of APEX1-dependent gene suppression. Vascular
CYP11B2 may contribute to stimulation of VSMCs osteo-/chondrogenic transformation
during hyperphosphatemia.
PMID- 28515449
TI - The role of stride frequency for walk-to-run transition in humans.
AB - It remains unclear why humans spontaneously shift from walking to running at a
certain point during locomotion at gradually increasing velocity. We show that a
calculated walk-to-run transition stride frequency (70.6 +/- 3.2 strides min-1)
agrees with a transition stride frequency (70.8 +/- 3.1 strides min-1) predicted
from the two stride frequencies applied during treadmill walking and running at
freely chosen velocities and freely chosen stride frequencies. The agreement is
based on Bland and Altman's statistics. We found no essential mean relative
difference between the two transition frequencies, i.e. -0.5% +/- 4.2%, as well
as limits of agreement of -8.7% and 7.7%. The particular two freely chosen stride
frequencies used for prediction are considered behavioural attractors. Gait is
predicted to be shifted from walking to running when the stride frequency starts
getting closer to the running attractor than to the walking attractor. In
particular, previous research has focussed on transition velocity and
optimisation theories based on minimisation of, e.g., energy turnover or
biomechanical loadings of the legs. Conversely, our data support that the central
phenomenon of walk-to-run transition during human locomotion could be influenced
by behavioural attractors in the form of stride frequencies spontaneously
occurring during behaviourally unrestricted gait conditions of walking and
running.
PMID- 28515450
TI - Microfluidic Sorting of Cells by Viability Based on Differences in Cell
Stiffness.
AB - The enrichment of viable cells is an essential step to obtain effective products
for cell therapy. While procedures exist to characterize the viability of cells,
most methods to exclude nonviable cells require the use of density gradient
centrifugation or antibody-based cell sorting with molecular labels of cell
viability. We report a label-free microfluidic technique to separate live and
dead cells that exploits differences in cellular stiffness. The device uses a
channel with repeated ridges that are diagonal with respect to the direction of
cell flow. Stiff nonviable cells directed through the channel are compressed and
translated orthogonally to the channel length, while soft live cells follow
hydrodynamic flow. As a proof of concept, Jurkat cells are enriched to high
purity of viable cells by a factor of 185-fold. Cell stiffness was validated as a
sorting parameter as nonviable cells were substantially stiffer than live cells.
To highlight the utility for hematopoietic stem cell transplantation, frozen
samples of cord blood were thawed and the purity of viable nucleated cells was
increased from 65% to over 94% with a recovery of 73% of the viable cells. Thus,
the microfluidic stiffness sorting can simply and efficiently obtain highly pure
populations of viable cells.
PMID- 28515451
TI - HOXA7, HOXA9, and HOXA10 are differentially expressed in clival and sacral
chordomas.
AB - Chordomas are rare tumours of the bone arising along the spine from clivus to
sacrum. We compared three chordoma cell lines of the clivus region including the
newly established clivus chordoma cell line, U-CH14, with nine chordoma cell
lines originating from sacral primaries by morphology, on genomic and expression
levels and with patient samples from our chordoma tissue bank. Clinically,
chordomas of the clivus were generally smaller in size at presentation and
patients with sacral chordomas had more metastases and more often recurrent
disease. All chordoma cell lines had a typical physaliphorous morphology and
expressed brachyury, S100-protein and cytokeratin. By expression analyses we
detected differentially expressed genes in the clivus derived cell lines as
compared to the sacral cell lines. Among these were HOXA7, HOXA9, and HOXA10
known to be important for the development of the anterior-posterior body axis.
These results were confirmed by qPCR. Immunohistologically, clivus chordomas had
no or very low levels of HOXA10 protein while sacral chordomas showed a strong
nuclear positivity in all samples analysed. This differential expression of HOX
genes in chordomas of the clivus and sacrum suggests an oncofetal mechanism in
gene regulation linked to the anatomic site.
PMID- 28515452
TI - Trends and Outcomes of Surgical Treatment for Colorectal Cancer between 2004 and
2012- an Analysis using National Inpatient Database.
AB - Limited data are available for the epidemiology and outcome of colorectal cancer
in relation to the three main surgical treatment modalities (open, laparoscopic
and robotic). Using the US National Inpatient Sample database from 2004 to 2012,
we identified 1,265,684 hospitalized colorectal cancer patients. Over the 9 year
period, there was a 13.5% decrease in the number of hospital admissions and a
43.5% decrease in in-hospital mortality. Comparing the trend of surgical
modalities, there was a 35.4% decrease in open surgeries, a 3.5 fold increase in
laparoscopic surgeries, and a 41.3 fold increase in robotic surgeries.
Nonetheless, in 2012, open surgery still remained the preferred surgical
treatment modality (65.4%), followed by laparoscopic (31.2%) and robotic
surgeries (3.4%). Laparoscopic and robotic surgeries were associated with lower
in-hospital mortality, fewer complications, and shorter length of stays, which
might be explained by the elective nature of surgery and earlier tumor grades.
After excluding patients with advanced tumor grades, laparoscopic surgery was
still associated with better outcomes and lower costs than open surgery. On the
contrary, robotic surgery was associated with the highest costs, without
substantial outcome benefits over laparoscopic surgery. More studies are required
to clarify the cost-effectiveness of robotic surgery.
PMID- 28515453
TI - Validation of reference genes for the normalization of the RT-qPCR gene
expression of virulence genes of Erwinia amylovora in apple shoots.
AB - To study the expression of pathogenicity-related genes in Erwinia amylovora,
seven candidate reference genes (ffh, glyA, gyrA, proC, pykA, recA, rpoB) were
selected and validated with the following five different mathematic algorithms:
geNorm, NormFinder, BestKeeper, the delta CT method and the RefFinder web-based
tool. An overall comprehensive ranking output from each of the selected software
programs revealed that proC and recA, followed by ffh and pykA, were the most
stably expressed genes and can be recommended for the normalization of RT-qPCR
data. A combination of the three reference genes, proC, recA and ffh, allowed for
the accurate expression analysis of amsB and hrpN genes and the calculation of
their fold change in E. amylovora after its infection of susceptible and
resistant apple cultivars. To the best of our knowledge, this is the first study
presenting a list of the most suitable reference genes for use in the relative
quantification of target gene expression in E. amylovora in planta, selected on
the basis of a multi-algorithm analysis.
PMID- 28515454
TI - A quantitative shRNA screen identifies ATP1A1 as a gene that regulates
cytotoxicity by aurilide B.
AB - Genome-wide RNA interference (RNAi) with pooled and barcoded short-hairpin RNA
(shRNA) libraries provides a powerful tool for identifying cellular components
that are relevant to the modes/mechanisms of action (MoA) of bioactive compounds.
shRNAs that affect cellular sensitivity to a given compound can be identified by
deep sequencing of shRNA-specific barcodes. We used multiplex barcode sequencing
technology by adding sample-specific index tags to PCR primers during sequence
library preparation, enabling parallel analysis of multiple samples. An shRNA
library screen with this system revealed that downregulation of ATP1A1, an alpha
subunit of Na+/K+ ATPase, conferred significant sensitivity to aurilide B, a
natural marine product that induces mitochondria-mediated apoptosis. Combined
treatment with ouabain which inhibits Na+/K+ ATPase by targeting alpha-subunits
potentiated sensitivity to aurilide B, suggesting that ATP1A1 regulates
mitochondria-mediated apoptosis. Our results indicate that multiplex sequencing
facilitates the use of pooled shRNA library screening for the identification of
combination drug therapy targets.
PMID- 28515455
TI - Comparative genomic analysis reveals the environmental impacts on two
Arcticibacter strains including sixteen Sphingobacteriaceae species.
AB - How the genomic diversity of species is driven by geographical isolation and
environmental factors are not well understood for cold environments. Here, the
environmental stress responses of two phylogenetically close Arcticibacter
strains, A. eurypsychrophilus MJ9-5 and A. svalbardensis MN12-7, isolated from a
Tibetan Plateau glacier and Svalbard soil, were analyzed. The comparative genomic
analysis was performed with sixteen other related Sphingobacteriaceae species.
Analyses of the relationships between growth temperature and genome composition,
cold and heat shock genes showed that genomic adaption characteristics were more
obvious when the strains were grouped by their upper limit in growth temperature,
rather than by their minimal or optimal growth temperatures for
Sphingobacteriaceae species. The very divergent genetic distance of genome
fractions assigned to the functions of 'secondary metabolism', 'dormancy and
sporulation' and 'metabolism of aromatic compounds' indicated the heterogeneous
evolution of genes under different environmental pressures of the
Sphingobacteriaceae species. The greatest differences between strains MJ9-5 and
MN12-7 occurred in the genes devoted to the CRISPRs, osmotic adaption and
metabolism of monosaccharides, nitrogen and aromatic compounds. These
distinctions corresponded to two different environmental pressures, salinity and
nutritional level, in the glacier ice and Svalbard soil environments.
PMID- 28515456
TI - Metabolomic analysis shows differential hepatic effects of T2 and T3 in rats
after short-term feeding with high fat diet.
AB - Nonalcoholic fatty liver disease (NAFLD) is a major health problem worldwide, and
is often associated with lipotoxic injury, defective mitochondrial function, and
insulin resistance. Thyroid hormones (THs) are important regulators of hepatic
lipid metabolism. Among the THs, diiodothyronine (T2) and triiodothyronine (T3)
have shown promising results in lowering hepatic fat content in various models of
NAFLD. In this study, we used a targeted metabolomics approach to investigate the
differential effects of T2 and T3 on the early metabolic adaptation in the livers
of rats fed high fat diet (HFD), a period when hepatosteatosis is reversible. Our
results showed that both T2 and T3 strongly induced autophagy and intra-hepatic
acylcarnitine flux but prevented the generation of sphingolipid/ceramides in
animals fed HFD. Interestingly, although both T2 and T3 decreased hepatic fat
content, only T2 was able to rescue the impairment in AKT and MAPK/ERK pathways
caused by HFD. In summary, we have identified and characterized the effects of T2
and T3 on hepatic metabolism during short-term exposure to HFD. These findings
illuminate the common and divergent metabolic pathways by T2 and T3 that also may
be important in the prevention and treatment of NAFLD.
PMID- 28515457
TI - Crystal structure of TAZ-TEAD complex reveals a distinct interaction mode from
that of YAP-TEAD complex.
AB - The Hippo pathway is a tumor suppressor pathway that is implicated in the
regulation of organ size. The pathway has three components: the upstream
regulatory factors, the kinase core, and the downstream transcriptional
machinery, which consists of YAP, TAZ (transcription co-activators) and TEAD
(transcription factor). Formation of YAP/TAZ-TEAD complexes leads to the
transcription of growth-promoting genes. Herein, we report the crystal structure
of TAZ-TEAD4 complex, which reveals two binding modes. The first is similar to
the published YAP-TEAD structure. The second is a unique binding mode, whereby
two molecules of TAZ bind to and bridge two molecules of TEAD4. We validated the
latter using cross-linking and multi-angle light scattering. Using siRNA, we
showed that TAZ knockdown leads to a decrease in TEAD4 dimerization. Lastly,
results from luciferase assays, using YAP/TAZ transfected or knockdown cells,
give support to the non-redundancy of YAP/TAZ co-activators in regulating gene
expression in the Hippo pathway.
PMID- 28515458
TI - Floccular fossa size is not a reliable proxy of ecology and behaviour in
vertebrates.
AB - The cerebellar floccular and parafloccular lobes are housed in fossae of the
periotic region of the skull of different vertebrates. Experimental evidence
indicates that the lobes integrate visual and vestibular information and control
the vestibulo-ocular reflex, vestibulo-collic reflex, smooth pursuit and gaze
holding. Multiple paleoneuroanatomy studies have deduced the behaviour of fossil
vertebrates by measuring the floccular fossae (FF). These studies assumed that
there are correlations between FF volume and behaviour. However, these
assumptions have not been fully tested. Here, we used micro-CT scans of extant
mammals (47 species) and birds (59 species) to test six possible morphological
functional associations between FF volume and ecological/behavioural traits of
extant animals. Behaviour and ecology do not explain FF volume variability in
four out of six variables tested. Two variables with significant results require
further empirical testing. Cerebellum plasticity may explain the lack of
statistical evidence for the hypotheses tested. Therefore, variation in FF volume
seems to be better explained by a combination of factors such as anatomical and
phylogenetic evolutionary constraints, and further empirical testing is required.
PMID- 28515459
TI - Associations between Left Ventricular Cavity Size and Cardiac Function and
Overload Determined by Natriuretic Peptide Levels and a Covariance Structure
Analysis.
AB - The effects of left ventricular (LV) cavity size on cardiac function and overload
have not yet been fully elucidated. We performed a covariance structure analysis
and drew theoretical path models to clarify the effects of hemodynamic parameters
on the stroke volume index (SVI) as a marker of cardiac function and on the
plasma B-type natriuretic peptide (BNP) level as a marker of cardiac overload. We
simultaneously measured various hemodynamic parameters and the BNP levels during
cardiac catheterization in 1,715 inpatients of our institution. The current path
models tested the validity of the Frank-Starling law in patients with heart
failure using the SVI, the LV end-systolic volume index (LVESVI) and the LV end
diastolic volume index (LVEDVI). Using the BNP levels, the path models clearly
demonstrated that LVESVI substantially augmented cardiac overload, whereas LVEDVI
palliated this parameter. These volume indices exerted opposite effects on
cardiac function and overload. These results advance the understanding of the
relationships between LV cavity size and both cardiac function and overload and
indicate the increasing importance of LV diastolic volume in heart failure and
the utility of LVESVI as an important marker of cardiac remodeling for further
relevant studies.
PMID- 28515461
TI - Variation of Nanostructures, Molecular Interactions, and Anisotropic Elastic
Moduli of Lignocellulosic Cell Walls with Moisture.
AB - A combination of experimental, theoretical and numerical studies is used to
investigate the variation of elastic moduli of lignocellulosic (bamboo) fiber
cell walls with moisture content (MC). Our Nanoindentation results show that the
longitudinal elastic modulus initially increased to a maximum value at about 3%
MC and then decreased linearly with increasing MC. In contrast, the transverse
moduli decrease linearly with MC. We showed that amorphous materials in cell
walls have key roles in the variation of elastic modulus with increasing MC.
Elastic modulus of lignin, calculated by molecular dynamics simulations,
increases initially with increasing MC, and then decreases. In contrast, elastic
modulus of hemicellulose decreases constantly with MC. Below 10% MC, water
molecules tend to break hydrogen bonds between polymer chains and form new
hydrogen bond bridges between the polymer chains, while above 10% MC, water
molecules aggregate together and create nano-droplets inside the materials.
During the process of bridging, the fractional free volume of lignin decreases.
The free volume reduction along with formation of hydrogen bond bridges causes a
growth in elastic modulus of lignin at low MC. The constant increase of
hemicellulose free volume, however, causes the aggregation of voids in the system
and diminution of elastic properties.
PMID- 28515462
TI - Autoimmunity: HLA-mediated protection in Goodpasture disease.
PMID- 28515460
TI - Chlamydia trachomatis infection of human endometrial stromal cells induces
defective decidualisation and chemokine release.
AB - Miscarriage affects ~20% of pregnancies and maternal infections account for ~15%
of early miscarriages. Chlamydia trachomatis (Ct) has been associated with
miscarriage but the underlying mechanisms are unknown. Successful implantation
requires endometrial stromal cell (ESC) decidualisation. Maintenance of pregnancy
requires angiogenesis, establishment of the correct cellular milieu and
trophoblast invasion, all of which involve the action of chemokines. Our
objective was to determine whether Ct infection impacts upon ESC decidualisation
and chemokine secretion. Human primary ESC were decidualised in-vitro, infected
with Ct serovar E, and changes in expression of genes of interest were measured
using RT-PCR, proteomic array and ELISA. We demonstrate for the first time that
Ct can infect and proliferate in ESC. Expression of the decidualisation marker
prolactin was decreased in Ct-infected ESC at both mRNA and protein levels. Ct
infection altered the chemokine profile of decidualised ESC as shown by proteomic
array. Chemokines CXCL12 and CXCL16, important for trophoblast invasion, were
analysed further and expression was reduced in infected decidualised cells at
mRNA and protein levels. Our data indicate that Ct infection of ESC impairs
decidualisation and alters chemokine release. These findings at least partially
explain how Ct infection could result in adverse pregnancy outcomes.
PMID- 28515463
TI - Enzyme characteristics of pathogen-specific trehalose-6-phosphate phosphatases.
AB - Owing to the key role of trehalose in pathogenic organisms, there has recently
been growing interest in trehalose metabolism for therapeutic purposes. Trehalose
6-phosphate phosphatase (TPP) is a pivotal enzyme in the most prominent
biosynthesis pathway (OtsAB). Here, we compare the enzyme characteristics of
recombinant TPPs from five important nematode and bacterial pathogens, including
three novel members of this protein family. Analysis of the kinetics of trehalose
6-phosphate hydrolysis reveals that all five enzymes display a burst-like kinetic
behaviour which is characterised by a decrease of the enzymatic rate after the
pre-steady state. The observed super-stoichiometric burst amplitudes can be
explained by multiple global conformational changes in members of this enzyme
family during substrate processing. In the search for specific TPP inhibitors,
the trapping of the complex conformational transitions in TPPs during the
catalytic cycle may present a worthwhile strategy to explore.
PMID- 28515466
TI - Disentangling the intricate atomic short-range order and electronic properties in
amorphous transition metal oxides.
AB - Solid state materials with crystalline order have been well-known and
characterized for almost a century while the description of disordered materials
still bears significant challenges. Among these are the atomic short-range order
and electronic properties of amorphous transition metal oxides [aTMOs], that have
emerged as novel multifunctional materials due to their optical switching
properties and high-capacity to intercalate alkali metal ions at low voltages.
For decades, research on aTMOs has dealt with technological optimization.
However, it remains challenging to unveil their intricate atomic short-range
order. Currently, no systematic and broadly applicable methods exist to assess
atomic-size structure, and since electronic localization is structure-dependent,
still there are not well-established optical and electronic mechanisms for
modelling the properties of aTMOs. We present state-of-the-art systematic
procedures involving theory and experiment in a self-consistent computational
framework to unveil the atomic short-range order and its role for the electronic
properties. The scheme is applied to amorphous tungsten trioxide aWO3, which is
the most studied electrochromic aTMO in spite of its unidentified atomic-size
structure. Our approach provides a one-to-one matching of experimental data and
corresponding model structure from which electronic properties can be directly
calculated in agreement with the electronic transitions observed in the XANES
spectra.
PMID- 28515464
TI - Systems Immunology of Diabetes-Tuberculosis Comorbidity Reveals Signatures of
Disease Complications.
AB - Comorbid diabetes mellitus (DM) increases tuberculosis (TB) risk and adverse
outcomes but the pathological interactions between DM and TB remain incompletely
understood. We performed an integrative analysis of whole blood gene expression
and plasma analytes, comparing South Indian TB patients with and without DM to
diabetic and non-diabetic controls without TB. Luminex assay of plasma cytokines
and growth factors delineated a distinct biosignature in comorbid TBDM in this
cohort. Transcriptional profiling revealed elements in common with published TB
signatures from cohorts that excluded DM. Neutrophil count correlated with the
molecular degree of perturbation, especially in TBDM patients. Body mass index
and HDL cholesterol were negatively correlated with molecular degree of
perturbation. Diabetic complication pathways including several pathways linked to
epigenetic reprogramming were activated in TBDM above levels observed with DM
alone. Our data provide a rationale for trials of host-directed therapies in
TBDM, targeting neutrophilic inflammation and diabetic complication pathways to
address the greater morbidity and mortality associated with this increasingly
prevalent dual burden of communicable and non-communicable diseases.
PMID- 28515465
TI - Gender-specific differential expression of exosomal miRNA in synovial fluid of
patients with osteoarthritis.
AB - The pathogenesis of osteoarthritis (OA) is poorly understood, and therapeutic
approaches are limited to preventing progression of the disease. Recent studies
have shown that exosomes play a vital role in cell-to-cell communication, and
pathogenesis of many age-related diseases. Molecular profiling of synovial fluid
derived exosomal miRNAs may increase our understanding of OA progression and may
lead to the discovery of novel biomarkers and therapeutic targets. In this
article we report the first characterization of exosomes miRNAs from human
synovial fluid. The synovial fluid exosomes share similar characteristics (size,
surface marker, miRNA content) with previously described exosomes in other body
fluids. MiRNA microarray analysis showed OA specific exosomal miRNA of male and
female OA. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and
Genomes (KEGG) pathway analysis identified gender-specific target genes/signaling
pathways. These pathway analyses showed that female OA specific miRNAs are
estrogen responsive and target TLR (toll-like receptor) signaling pathways.
Furthermore, articular chondrocytes treated with OA derived extracellular
vesicles had decreased expression of anabolic genes and elevated expression of
catabolic and inflammatory genes. In conclusion, synovial fluid exosomal miRNA
content is altered in patients with OA and these changes are gender specific.
PMID- 28515467
TI - Thermal radiation of Er doped dielectric crystals: Probing the range of
applicability of the Kirchhoff's law.
AB - Kirchhoff's law of thermal radiation, relating emissivity and absorptance is
commonly formulated for opaque bodies in thermodynamic equilibrium with the
environment. However, in many systems of practical importance, both assumptions
are often not satisfied. We revisit the century-old law and examine the limits of
its applicability in an example of Er:YAG and Er:YLF dielectric crystals
potential radiation converters for thermophotovoltaic applications. The (80 at.%)
Er:YAG crystal is opaque between 1.45 MUm and 1.64 MUm. In this spectral range,
its absorptance alpha(lambda) is spectrally flat and differentiates from unity
only by a small amount of reflection. The shape of the emissivity spectrum
E(lambda) closely matches that of absorptance alpha(lambda), implying that the
Kirchhoff's law can adequately describe thermal radiation of opaque bodies, even
if thermodynamic equilibrium is not satisfied. The (20 at.%) Er:YLF crystal had
smaller size, lower concentration of Er ions, and it was not opaque.
Nevertheless, its spectrum of emissivity had almost the same shape (between 1.45
MUm and 1.62 MUm) as the absorptance derived from the transmission measurements.
Our results are consistent with the conclusion that the Kirchhoff's law of
thermal radiation can be extended (with caution) to not-opaque bodies away from
the thermodynamic equilibrium.
PMID- 28515468
TI - Cardiolipin content, linoleic acid composition, and tafazzin expression in
response to skeletal muscle overload and unload stimuli.
AB - Cardiolipin (CL) is a unique mitochondrial phospholipid that, in skeletal muscle,
is enriched with linoleic acid (18:2n6). Together, CL content and CL 18:2n6
composition are critical determinants of mitochondrial function. Skeletal muscle
is comprised of slow and fast fibers that have high and low mitochondrial
content, respectively. In response to overloading and unloading stimuli, these
muscles undergo a fast-to-slow oxidative fiber type shift and a slow-to-fast
glycolytic fiber type shift, respectively, with a concomitant change in
mitochondrial content. Here, we examined changes in CL content and CL 18:2n6
composition under these conditions along with tafazzin (Taz) protein, which is a
transacylase enzyme that generates CL lipids enriched with 18:2n6. Our results
show that CL content, CL 18:2n6 composition, and Taz protein content increased
with an overload stimulus in plantaris. Conversely, CL content and CL 18:2n6
composition was reduced with an unloaded stimulus in soleus. Interestingly, Taz
protein was increased in the unloaded soleus, suggesting that Taz may provide
some form of compensation for decreased CL content and CL 18:2n6 composition.
Together, this study highlights the dynamic nature of CL and Taz in skeletal
muscle, and future studies will examine the physiological significance behind the
changes in CL content, CL 18:2n6 and Taz.
PMID- 28515469
TI - The Topobiology of Chemical Elements in Seabird Feathers.
AB - The highly organized morphogenesis of bird feathers holds important phylo- and
ontogenetic information on the evolution of birds, organogenesis, tissue
regeneration, and the health status of individual animals. Altered topobiological
patterns are regularly used as retrospective evidence for disturbed developmental
trajectories due to the past exposure to environmental stressors. Using the most
advanced high-resolution (5-70 um) X-ray fluorescence microscopy (XFM), we
describe in the feathers from three species of Procellariiformes hitherto
unknown, depositions of elements (Zn, Ca, Br, Cu, Fe) that are independent of
pigmentation or any underlying variation in density or polymer structure. In the
case of Zn, the pattern across several species of Procellariiformes, but not
other species, consisted of highly regular bands of Zn numbering 30-32, which may
reflect the estimated number of days of active feather growth or the duration of
the moult period. Thus, speculatively, the highly consistent Zn pattern might be
the result of a so far unknown diurnal systemic regulation rather than local
heterogeneity amongst the follicular stem cells.
PMID- 28515470
TI - A novel missense mutation in the HECT domain of NEDD4L identified in a girl with
periventricular nodular heterotopia, polymicrogyria and cleft palate.
AB - We identified a novel de novo heterozygous missense mutation in the NEDD4L gene
(NM_015277: c.2617G>A; p.Glu873Lys) through whole-exome sequencing in a 3-year
old girl showing severe global developmental delay, infantile spasms, cleft
palate, periventricular nodular heterotopia and polymicrogyria. Mutations in the
HECT domain of NEDD4L have been reported in patients with a neurodevelopmental
disorder along with similar brain malformations. All patients reported with
NEDD4L HECT domain mutations showed periventricular nodular heterotopia, and most
had seizures, cortex anomalies, cleft palate and syndactyly. The unique
constellation of clinical features in patients with NEDD4L mutations might help
clinically distinguish them from patients with other genetic mutations including
FLNA, which is a well-known causative gene of periventricular nodular
heterotopia. Although mutations in the HECT domain of NEDD4L that lead to AKT
mTOR pathway deregulation in forced expression system were reported, our western
blot analysis did not show an increased level of AKT-mTOR activity in
lymphoblastoid cell lines (LCLs) derived from the patient. In contrast to the
forced overexpression system, AKT-mTOR pathway deregulation in LCLs derived from
our patient seems to be subtle.
PMID- 28515472
TI - Carrier frequency of Wilson's disease in the Korean population: a DNA-based
approach.
AB - Wilson's disease (WD) is an autosomal recessive disorder caused by ATP7B gene
mutation. The frequency of WD is about 1 in 30 000 worldwide. In the present
study, we screened 14 835 dried blood spots (DBSs) from asymptomatic Korean
neonates and retrospectively reviewed massively parallel sequencing of 1090
control individuals to estimate carrier frequency. TaqMan real-time PCR assays
were conducted to detect six mutations that account for 58.3% of mutations in
Korean WD patients: c.2333G>T (p.Arg778Leu), c.2621C>T (p.Ala874Val), c.3086C>T
(p.Thr1029Ile), c.3247C>T (p.Leu1083Phe), c.3556G>A (p.Gly1186Ser) and c.3809A>G
(p.Asn1270Ser). We also retrospectively reviewed data from 1090 individuals with
various indications other than WD for whom whole-exome or panel sequencing data
were available. Mutant allele frequency based on the six most common mutations
was 0.0067 among the total of 14 835 DBSs screened. Given that these six
mutations account for 58.3% of mutations in Korean WD patients, the corrected
mutant allele frequency is 0.0115 (95% confidence interval (CI): 0.0103-0.0128).
Corresponding incidence (q2) and carrier frequency (2pq) were estimated to be
1:7561 and 1:44, respectively. In retrospective data analysis of 1090 control
individuals, allele frequency of pathogenic or likely pathogenic variants was
0.0096 (95% CI: 0.0063-0.0146). Corresponding carrier frequency was estimated to
be 1:53. Estimated allele and carrier frequencies based on DNA screening were
relatively higher than those reported previously based on clinical ascertainment.
PMID- 28515471
TI - Clinical and molecular investigation of 14 Japanese patients with complete TFP
deficiency: a comparison with Caucasian cases.
AB - Mitochondrial trifunctional protein (TFP) deficiency is an inherited metabolic
disorder of mitochondrial fatty-acid oxidation. Isolated long-chain 3-hydroxyacyl
CoA dehydrogenase deficiency is often reported in Caucasian countries due to a
common mutation. However, the molecular and clinical basis of complete TFP
deficiency has not been extensively reported. In this study, 14 Japanese cases
(13 families) with complete TFP deficiency, including 9 previously reported
cases, were analyzed to clarify the clinical and molecular characteristics of TFP
deficiency. The clinical types of the 14 patients were as follows: 12 cases of
neonatal (n=7) or myopathic (n=5) types and 2 cases of intermediate type.
Peripheral neuropathy was found in four cases and hypocalcemia due to
hypoparathyroidism, which is rarely reported in Caucasian patients, had developed
in four cases. Maternal hemolysis, elevated liver enzymes and low platelet count
syndrome and acute fatty liver of pregnancy were noted in two and one mothers,
respectively. Fourteen mutations were identified in 26 alleles in Japanese
patients, including two novel mutations (HADHA: c.361C>T, and HADHA-HADHB:
g.26233880_ 26248855del), although no common mutations were found. This study
suggests that the molecular and clinical aspects of Japanese patients with TFP
deficiencies differ from those of Caucasian patients.
PMID- 28515473
TI - Placental O-GlcNAc-transferase expression and interactions with the
glucocorticoid receptor are sex specific and regulated by maternal corticosterone
exposure in mice.
AB - Maternal stress programs offspring disease in a sexually dimorphic manner with
males often more adversely affected. Previous studies of maternal glucocorticoid
exposure suggest male vulnerability may derive from placental alterations. The
hexosamine signalling pathway and O-linked glycosylation (O-GlcNAcylation) are
part of an essential adaptive survival response in healthy cells. The key enzyme
involved is O-linked-N-acetylglucosamine transferase (OGT), a gene recently
identified as a sex-specific placental biomarker of maternal stress. Using a
mouse model of maternal corticosterone (Cort) exposure, we examined components of
hexosamine biosynthesis/signalling and O-GlcNAcylation in whole placentae at
E14.5. Our results demonstrate sex-specific differences in OGT levels and O
GlcNAcylation during Cort exposure which impacts on key mediators of cell
survival, in particular AKT as well as the stress responsive OGT/GR
transrepression complex. In male placentae only, Cort exposure increased Akt O
GlcNacylation which correlated with decreased phosphorylation. Female placentae
had higher basal OGT and OGT/GR complex compared with male placentae. Cort
exposure did not alter these levels in female placentae but increased global O
GlcNacylation. In male placentae Cort increased OGT and OGT/GR complex with no
change in global O-GlcNacylation. These findings suggest that sex-specific
differences in placental OGT play a key role in the sexually dimorphic responses
to stress.
PMID- 28515475
TI - Distinguishing physical mechanisms using GISAXS experiments and linear theory:
the importance of high wavenumbers.
AB - In this work we analyze GISAXS measurements of the structure factor of Si
surfaces evolving during 1 keV Ar+ ion bombardment. Using newly-developed methods
sensitive to the full range of experimentally-available wavenumbers q, we extract
the linear amplification rate R(q) governing surface stability over a range of
wavenumbers 4-5 times larger than has previously been obtained. Comparing with
theoretical models also retaining full wavenumber-dependence, we find an
excellent fit of the experimental data over the full range of irradiation angles
and wavenumbers. Moreover, the fitted parameter values represent experimental
evaluation of the magnitudes of most physical mechanisms currently believed to be
important to the pattern-formation process. In all cases, the extracted values
agree well with direct observations or atomistic simulations of the same
quantities, suggesting that GISAXS analysis may allow more powerful comparison
between experiment and theory than had previously been thought.
PMID- 28515474
TI - Blunted Ambiguity Aversion During Cost-Benefit Decisions in Antisocial
Individuals.
AB - Antisocial behavior is often assumed to reflect aberrant risk processing.
However, many of the most significant forms of antisocial behavior, including
crime, reflect the outcomes of decisions made under conditions of ambiguity
rather than risk. While risk and ambiguity are formally distinct and
experimentally dissociable, little is known about ambiguity sensitivity in
individuals who engage in chronic antisocial behavior. We used a financial
decision-making task in a high-risk community-based sample to test for
associations between sensitivity to ambiguity, antisocial behavior, and arrest
history. Sensitivity to ambiguity was lower in individuals who met diagnostic
criteria for Antisocial Personality Disorder. Lower ambiguity sensitivity was
also associated with higher externalizing (but not psychopathy) scores, and with
higher levels of aggression (but not rule-breaking). Finally, blunted sensitivity
to ambiguity also predicted a greater frequency of arrests. Together, these data
suggest that alterations in cost-benefit decision-making under conditions of
ambiguity may promote antisocial behavior.
PMID- 28515476
TI - Spin-orbit-torque-induced magnetic domain wall motion in Ta/CoFe nanowires with
sloped perpendicular magnetic anisotropy.
AB - In materials with the gradient of magnetic anisotropy, spin-orbit-torque-induced
magnetization behaviour has attracted attention because of its intriguing
scientific principle and potential application. Most of the magnetization
behaviours microscopically originate from magnetic domain wall motion, which can
be precisely depicted using the standard cooperative coordinate method (CCM).
However, the domain wall motion in materials with the gradient of magnetic
anisotropy using the CCM remains lack of investigation. In this paper, by
adopting CCM, we established a set of equations to quantitatively depict the spin
orbit-torque-induced motion of domain walls in a Ta/CoFe nanotrack with weak
Dzyaloshinskii-Moriya interaction and magnetic anisotropy gradient. The equations
were solved numerically, and the solutions are similar to those of a
micromagnetic simulation. The results indicate that the enhanced anisotropy along
the track acts as a barrier to inhibit the motion of the domain wall. In
contrast, the domain wall can be pushed to move in a direction with reduced
anisotropy, with the velocity being accelerated by more than twice compared with
that for the constant anisotropy case. This substantial velocity manipulation by
anisotropy engineering is important in designing novel magnetic information
devices with high reading speeds.
PMID- 28515478
TI - Molecular phylogenetics and biogeography of the mint tribe Elsholtzieae
(Nepetoideae, Lamiaceae), with an emphasis on its diversification in East Asia.
AB - Elsholtzia and its allied genera such as Collinsonia and Perilla (tribe
Elsholtzieae, Lamiaceae) are an ecologically and economically important plant
group consisting of ~71 species, with most species distributed in East and
Southeast Asia, and several species in North America. Their phylogeny and
historical biogeography resulting in a distant intercontinental disjunction are
poorly understood. Here we use two nuclear (ETS, ITS) and five chloroplast (rbcL,
matK, trnL-F, ycf1, ycf1-rps15) fragments to reconstruct the phylogeny,
biogeographic history, and patterns of diversification of Elsholtzieae. The tribe
Elsholtzieae is monophyletic and divided into five clades. The woody Elsholtzia
species are nested within herbaceous ones and are inferred to have evolved from
herbaceous ancestors. Molecular dating shows that the five major clades were
established during the Eocene period, but most of the modern diversity did not
originate until the Miocene. The divergence between the New World Collinsonia and
the Old World Mosla-Keiskea-Perilla clade was dated to the mid-Miocene. Ancestral
area reconstructions suggest that the tribe originated in East Asia, and then
dispersed to Southeast Asia and North America. Overall, our findings highlight
the important roles of the uplifts of the Qinghai-Tibetan Plateau (QTP) and
climate changes from Middle Miocene onwards in promoting species diversification
of Elsholtzieae.
PMID- 28515477
TI - Cancer cachexia associates with a systemic autophagy-inducing activity mimicked
by cancer cell-derived IL-6 trans-signaling.
AB - The majority of cancer patients with advanced disease experience weight loss,
including loss of lean body mass. Severe weight loss is characteristic for cancer
cachexia, a condition that significantly impairs functional status and survival.
The underlying causes of cachexia are incompletely understood, and currently no
therapeutic approach can completely reverse the condition. Autophagy coordinates
lysosomal destruction of cytosolic constituents and is systemically induced by
starvation. We hypothesized that starvation-mimicking signaling compounds
secreted from tumor cells may cause a systemic acceleration of autophagy during
cachexia. We found that IL-6 secreted by tumor cells accelerates autophagy in
myotubes when complexed with soluble IL-6 receptor (trans-signaling). In lung
cancer patients, were cachexia is prevalent, there was a significant correlation
between elevated IL-6 expression in the tumor and poor prognosis of the patients.
We found evidence for an autophagy-inducing bioactivity in serum from cancer
patients and that this is clearly associated with weight loss. Importantly, the
autophagy-inducing bioactivity was reduced by interference with IL-6 trans
signaling. Together, our findings suggest that IL-6 trans-signaling may be
targeted in cancer cachexia.
PMID- 28515479
TI - Acquisition of virulence factors in livestock-associated MRSA: Lysogenic
conversion of CC398 strains by virulence gene-containing phages.
AB - Staphylococcus aureus MRSA strains belonging to the clonal complex 398 (CC398)
are highly prevalent in livestock and companion animals but may also cause
serious infections in humans. CC398 strains in livestock usually do not possess
well-known virulence factors that can be frequently found in other MRSA sequence
types (ST). Since many staphylococcal virulence genes are residing on the genomes
of temperate phages, the question arises why livestock-associated (LA-) CC398
strains are only rarely infected by those phages. We isolated and characterized
four temperate phages (P240, P282, P630 and P1105) containing genes of the immune
evasion cluster (IEC) and/or for the Panton-Valentine leucocidin (PVL). Sequence
analysis of the phage genomes showed that they are closely related to known
phages and that the DNA region encoding lysis proteins, virulence factors and the
integrase exhibits numerous DNA repeats which may facilitate genomic
rearrangements. All phages lysed and lysogenized LA-CC398 strains. Integration of
IEC phage P282 was detected at ten sites of the hosts' chromosome. The prophages
were stably inherited in LA-CC398 and enterotoxin A, staphylokinase and PVL toxin
were produced. The data demonstrate that lysogenic conversion of LA-CC398 strains
by virulence-associated phages may occur and that new pathotypes may emerge by
this mechanism.
PMID- 28515480
TI - Weak stromal Caveolin-1 expression in colorectal liver metastases predicts poor
prognosis after hepatectomy for liver-only colorectal metastases.
AB - Loss of stromal Caveolin-1 (CAV1) expression is associated with poor prognosis in
various cancers. We evaluated the prognostic value of CAV1 expression of both
cancer cells and stromal cells in colorectal liver metastases (CRLM) in patients
undergoing hepatectomy. In this retrospective study, 109 patients were enrolled.
CAV1 expression was studied by immunohistochemistry. The staining was scored
semiquantitatively as weak or strong. Disease-free survival (DFS) and overall
survival (OS) were calculated using both Kaplan-Meier and multivariate
Coxregression methods. Weak stromal CAV1 expression was associated with decreased
DFS and OS in univariate and in multivariate analysis (HR 2.00; 95% CI, 1.24
3.22; P = 0.004, and HR 2.47; 95% CI, 1.28-4.76; P = 0.007, respectively). Cancer
cell CAV1 expression was not associated with DFS and OS. Five-year DFS and OS
rates were 13% and 43%, respectively, in patients with weak stromal CAV1
expression and 40% and 71%, respectively, in patients with strong stromal CAV1
expression. In this study, we indicate that weak stromal CAV1 expression in CRLM
is an adverse prognostic factor in patients who undergo liver resection for liver
only colorectal metastases. We suggest validation of this finding in an
independent cohort and consideration of risk stratification for post-hepatectomy
adjuvant follow-up and therapy.
PMID- 28515482
TI - Precise and diffraction-limited waveguide-to-free-space focusing gratings.
AB - We present the design and characterization of waveguide grating devices that
couple visible-wavelength light at lambda = 674 nm from single-mode, high index
contrast dielectric waveguides to free-space beams forming micron-scale
diffraction-limited spots a designed distance and angle from the grating. With a
view to application in spatially-selective optical addressing, and in contrast to
previous work on similar devices, deviations from the main Gaussian lobe up to 25
microns from the focus and down to the 5 * 10-6 level in relative intensity are
characterized as well; we show that along one dimension the intensity of these
weak sidelobes approaches the limit imposed by diffraction from the finite field
extent in the grating region. Additionally, we characterize the polarization
purity in the focal region, observing at the center of the focus a low impurity
<3 * 10-4 in relative intensity. Our approach allows quick, intuitive design of
devices with such performance, which may be applied in trapped-ion quantum
information processing and generally in any systems requiring optical routing to
or from objects 10 s-100 s of microns from a chip surface, but benefitting from
the parallelism and density of planar-fabricated dielectric integrated optics.
PMID- 28515481
TI - Conserved presence of G-quadruplex forming sequences in the Long Terminal Repeat
Promoter of Lentiviruses.
AB - G-quadruplexes (G4s) are secondary structures of nucleic acids that
epigenetically regulate cellular processes. In the human immunodeficiency
lentivirus 1 (HIV-1), dynamic G4s are located in the unique viral LTR promoter.
Folding of HIV-1 LTR G4s inhibits viral transcription; stabilization by G4
ligands intensifies this effect. Cellular proteins modulate viral transcription
by inducing/unfolding LTR G4s. We here expanded our investigation on the presence
of LTR G4s to all lentiviruses. G4s in the 5'-LTR U3 region were completely
conserved in primate lentiviruses. A G4 was also present in a cattle-infecting
lentivirus. All other non-primate lentiviruses displayed hints of less stable
G4s. In primate lentiviruses, the possibility to fold into G4s was highly
conserved among strains. LTR G4 sequences were very similar among
phylogenetically related primate viruses, while they increasingly differed in
viruses that diverged early from a common ancestor. A strong correlation between
primate lentivirus LTR G4s and Sp1/NFkappaB binding sites was found. All LTR G4s
folded: their complexity was assessed by polymerase stop assay. Our data support
a role of the lentiviruses 5'-LTR G4 region as control centre of viral
transcription, where folding/unfolding of G4s and multiple recruitment of factors
based on both sequence and structure may take place.
PMID- 28515483
TI - Refuges and host shift pathways of host-specialized aphids Aphis gossypii.
AB - Polyphagous cotton-melon aphid populations usually comprise cotton- and cucurbit
specialized biotypes. Host-specialized aphids are prone to food shortages.
Cucumber, the favourite food of cucurbit-specialized aphids, is usually absent
during autumn and winter in Nanjing, China. Therefore, suboptimal host plants act
as refuges and govern the population dynamics of this aphid. The species, growth
stages and leaf ages of host plants that cotton- and cucurbit-specialized aphids
potentially could use were explored in this study. Cotton-specialized aphids were
found to use wild chrysanthemum, potato, zucchini, pumpkin and flowering cucumber
besides cotton, whilst cucurbit-specialized aphids were able to utilize potato,
zucchini, pumpkin and mature cotton besides cucumber. The population dynamics and
genotype frequencies of aphids on hibiscus, cotton, zucchini, cucumber and
pumpkin showed that cotton-melon aphids on cucumber could transfer onto mature
cotton. Aphids on zucchini shared microsatellite genotypes with aphids on cotton
and cucumber. The predominant genotype of aphids on cotton was found on hibiscus,
but the predominant genotype on cucumber was not found on hibiscus. Host
specialized aphids clearly have refuges during food shortages. Hibiscus is an
overwintering host for cotton-specialized aphids but not for cucurbit-aphids.
Removing refuges or managing aphids on refuges could potentially be an effective
method to control cotton-melon aphids.
PMID- 28515484
TI - The complex tibial organ of the New Zealand ground weta: sensory adaptations for
vibrational signal detection.
AB - In orthopteran insects, a complex tibial organ has evolved to detect substrate
vibrations and/or airborne sound. Species of New Zealand weta (Anostostomatidae)
with tympanal ears on the foreleg tibia use this organ to communicate by sound,
while in atympanate species (which communicate by substrate drumming) the organ
is unstudied. We investigated the complex tibial organ of the atympanate ground
weta, Hemiandrus pallitarsis, for vibration detection adaptations. This system
contains four sensory components (subgenual organ, intermediate organ, crista
acustica homolog, accessory organ) in all legs, together with up to 90
scolopidial sensilla. Microcomputed tomography shows that the subgenual organ
spans the hemolymph channel, with attachments suggesting that hemolymph
oscillations displace the organ in a hinged-plate fashion. Subgenual sensilla are
likely excited by substrate oscillations transmitted within the leg. Instead of
the usual suspension within the middle of the tibial cavity, we show that the
intermediate organ and crista acustica homolog comprise a cellular mass broadly
attached to the anterior tibial wall. They likely detect cuticular vibrations,
and not airborne sound. This atympanate complex tibial organ shows elaborate
structural changes suggesting detection of vibrational stimuli by parallel input
pathways, thus correlating well with the burrowing lifestyle and communication by
substrate-transmitted vibration.
PMID- 28515485
TI - E-cigarettes induce toxicological effects that can raise the cancer risk.
AB - Electronic cigarettes (e-cigs) are devices designed to deliver nicotine in a
vaping solution rather than smoke and without tobacco combustion. Perceived as a
safer alternative to conventional cigarettes, e-cigs are aggressively marketed as
lifestyle-choice consumables, thanks to few restrictions and a lack of regulatory
guidelines. E-cigs have also gained popularity among never-smokers and teenagers,
becoming an emergent public health issue. Despite the burgeoning worldwide
consumption of e-cigs, their safety remains largely unproven and it is unknown
whether these devices cause in vivo toxicological effects that could contribute
to cancer. Here we demonstrate the co-mutagenic and cancer-initiating effects of
e-cig vapour in a rat lung model. We found that e-cigs have a powerful booster
effect on phase-I carcinogen-bioactivating enzymes, including activators of
polycyclic aromatic hydrocarbons (PAHs), and increase oxygen free radical
production and DNA oxidation to 8-hydroxy-2'-deoxyguanosine. Furthermore, we
found that e-cigs damage DNA not only at chromosomal level in peripheral blood,
such as strand breaks in leucocytes and micronuclei formation in reticulocytes,
but also at gene level such as point mutations in urine. Our results demonstrate
that exposure to e-cigs could endanger human health, particularly among younger
more vulnerable consumers.
PMID- 28515486
TI - Prognostic significance of TCF21 mRNA expression in patients with lung
adenocarcinoma.
AB - Several prognostic indicators have shown inconsistencies in patients of different
genders with lung adenocarcinoma, indicating that these variations may be due to
the different genetic background of males and females with lung adenocarcinoma.
In this study, we first used the Gene-Cloud of Biotechnology Information (GCBI)
bioinformatics platform to identify differentially expressed genes (DEGs) that
eliminated gender differences between lung adenocarcinoma and normal lung
tissues. Then, we screened out that transcription factor 21 (TCF21) is a hub gene
among these DEGs by creating a gene co-expression network on the GCBI platform.
Furthermore, we used the comprehensive survival analysis platforms Kaplan-Meier
plotter and PrognoScan to assess the prognostic value of TCF21 expression in lung
adenocarcinoma patients. Finally, we concluded that decreased mRNA expression of
TCF21 is a predictor for poor prognosis in patients with lung adenocarcinoma.
PMID- 28515488
TI - Learning and memory: A state to remember.
PMID- 28515487
TI - Functional interaction between FUS and SMN underlies SMA-like splicing changes in
wild-type hFUS mice.
AB - Several of the identified genetic factors in Amyotrophic Lateral Sclerosis (ALS)
point to dysfunction in RNA processing as a major pathogenic mechanism. However,
whether a precise RNA pathway is particularly affected remains unknown. Evidence
suggests that FUS, that is mutated in familial ALS, and SMN, the causative factor
in Spinal Muscular Atrophy (SMA), cooperate to the same molecular pathway, i.e.
regulation of alternative splicing, and that disturbances in SMN-regulated
functions, either caused by depletion of SMN protein (as in the case of SMA) or
by pathogenic interactions between FUS and SMN (as in the case of ALS) might be a
common theme in both diseases. In this work, we followed these leads and tested
their pathogenic relevance in vivo. FUS-associated ALS recapitulates, in
transgenic mice, crucial molecular features that characterise mouse models of
SMA, including defects in snRNPs distribution and in the alternative splicing of
genes important for motor neurons. Notably, altering SMN levels by
haploinsufficiency or overexpression does not impact the phenotypes of mouse or
Drosophila models of FUS-mediated toxicity. Overall, these findings suggest that
FUS and SMN functionally interact and that FUS may act downstream of SMN
regulated snRNP assembly in the regulation of alternative splicing and gene
expression.
PMID- 28515489
TI - Brain evolution: Genetic layering.
PMID- 28515490
TI - Neuronal development: The source of the signal.
PMID- 28515493
TI - Sleep: Dream a little dream.
PMID- 28515494
TI - Ligand chain length drives activation of lipid G protein-coupled receptors.
AB - Sphingosine-1-phosphate (S1P) is a lipid mediator that can activate five cell
membrane G protein-coupled receptors (GPCRs) which carry a variety of essential
functions and are promising drug targets. S1P is composed of a polar zwitterionic
head-group and a hydrophobic alkyl chain. This implies an activation mechanism of
its cognate receptor that must be significantly different from what is known for
prototypical GPCRs (ie receptor to small hydrophilic ligands). Here we aim to
identify the structural features responsible for S1P agonism by combining
molecular dynamics simulations and functional assays using S1P analogs of
different alkyl chain lengths. We propose that high affinity binding involves
polar interactions between the lipid head-group and receptor side chains while
activation is due to hydrophobic interactions between the lipid tail and residues
in a distinct binding site. We observe that ligand efficacy is directly related
to alkyl chain length but also varies with receptor subtypes in correlation with
the size of this binding pocket. Integrating experimental and computational data,
we propose an activation mechanism for the S1P receptors involving agonist
induced conformational events that are conserved throughout class A GPCRs.
PMID- 28515491
TI - The emerging field of epigenetics in neurodegeneration and neuroprotection.
AB - Epigenetic mechanisms - including DNA methylation, histone post-translational
modifications and changes in nucleosome positioning - regulate gene expression,
cellular differentiation and development in almost all tissues, including the
brain. In adulthood, changes in the epigenome are crucial for higher cognitive
functions such as learning and memory. Striking new evidence implicates the
dysregulation of epigenetic mechanisms in neurodegenerative disorders and
diseases. Although these disorders differ in their underlying causes and
pathophysiologies, many involve the dysregulation of restrictive element 1
silencing transcription factor (REST), which acts via epigenetic mechanisms to
regulate gene expression. Although not somatically heritable, epigenetic
modifications in neurons are dynamic and reversible, which makes them good
targets for therapeutic intervention.
PMID- 28515495
TI - The Failure Envelope Concept Applied To The Bone-Dental Implant System.
AB - Dental implants interact with the jawbone through their common interface. While
the implant is an inert structure, the jawbone is a living one that reacts to
mechanical stimuli. Setting aside mechanical failure considerations of the
implant, the bone is the main component to be addressed. With most failure
criteria being expressed in terms of stress or strain values, their fulfillment
can mean structural flow or fracture. However, in addition to those effects, the
bony structure is likely to react biologically to the applied loads by
dissolution or remodeling, so that additional (strain-based) criteria must be
taken into account. While the literature abounds in studies of particular loading
configurations, e.g. angle and value of the applied load to the implant, a
general study of the admissible implant loads is still missing. This paper
introduces the concept of failure envelopes for the dental implant-jawbone
system, thereby defining admissible combinations of vertical and lateral loads
for various failure criteria of the jawbone. Those envelopes are compared in
terms of conservatism, thereby providing a systematic comparison of the various
failure criteria and their determination of the admissible loads.
PMID- 28515492
TI - The brain, sirtuins, and ageing.
AB - In mammals, recent studies have demonstrated that the brain, the hypothalamus in
particular, is a key bidirectional integrator of humoral and neural information
from peripheral tissues, thus influencing ageing both in the brain and at the
'systemic' level. CNS decline drives the progressive impairment of cognitive,
social and physical abilities, and the mechanisms underlying CNS regulation of
the ageing process, such as microglia-neuron networks and the activities of
sirtuins, a class of NAD+-dependent deacylases, are beginning to be understood.
Such mechanisms are potential targets for the prevention or treatment of age
associated dysfunction and for the extension of a healthy lifespan.
PMID- 28515496
TI - Do Different Methods for Modeling Age-Graded Trajectories Yield Consistent and
Valid Results?
AB - Data on age-sequenced trajectories of individuals' attributes are used for a
growing number of research purposes. However, there is no consensus about which
method to use to identify the number of discrete trajectories in a population or
to assign individuals to a specific trajectory group. We modeled real and
simulated trajectory data using "naive" methods, optimal matching, grade of
membership models, and three types of finite mixture models. We found that these
methods produced inferences about the number of trajectories that frequently
differ (1) from one another and (2) from the truth as represented by simulation
parameters. We also found that they differed in the assignment of individuals to
trajectory groups. In light of these findings, we argue that researchers should
interpret results based on these methods cautiously, neither reifying point
estimates about the number of trajectories nor treating individuals' trajectory
group assignments as certain.
PMID- 28515498
TI - Using Lean to Develop Frontline Clinical Staff Pharmacists as Residency Program
Primary Preceptors.
PMID- 28515499
TI - Comment on Tapentadol and Serotonin Syndrome.
PMID- 28515497
TI - Invasion dynamics of Asian hornet, Vespa velutina (Hymenoptera: Vespidae): a case
study of a commune in south-west France.
AB - Asian hornet, Vespa velutina Lepeletier nests were discovered in 2007 in Andernos
les-Bains on the south-west coast of France, 3 years after the first reported
sightings in France. The number of nests increased in the commune over the
following 7 years, despite local authorities enacting a destruction policy. The
nests existed in close proximity to one another leading to a high density of over
10 nests per square kilometre in urban areas. New information on the chosen
habitat for nests is presented, and the differences between primary and secondary
locations are evident, with primary nests mostly occupying buildings and man-made
structures, while secondary nests were found on trees. Using Bayesian inference
methods, we fit a basic model to the observational data, which allows us to
estimate key demographic parameters. This model fit is highly informative for
predicting V. velutina spread and colonisation of other at-risk regions, and
suggests that local control has a limited impact on the spread of V. velutina
once established within a region.
PMID- 28515500
TI - Comment on "Probable Tapentadol-Associated Serotonin Syndrome After Overdose".
PMID- 28515501
TI - ISMP Medication Error Report Analysis: Potential Issues with New Basal
Insulin/GLP-1 Fixed Combinations Hydroxyzine-Hydroxyurea Mix-up Concomitant Use
of Entresto and ACE Inhibitors Can Lead to Serious Outcomes More Outpatient Oral
Cancer Drugs Should Be in Blister Packs.
AB - These medication errors have occurred in health care facilities at least once.
They will happen again-perhaps where you work. Through education and alertness of
personnel and procedural safeguards, they can be avoided. You should consider
publishing accounts of errors in your newsletters and/or presenting them at your
inservice training programs. Your assistance is required to continue this
feature. The reports described here were received through the Institute for Safe
Medication Practices (ISMP) Medication Errors Reporting Program. Any reports
published by ISMP will be anonymous. Comments are also invited; the writers'
names will be published if desired. ISMP may be contacted at the address shown
below. Errors, close calls, or hazardous conditions may be reported directly to
ISMP through the ISMP Web site (www.ismp.org, by calling 800-FAIL-SAFE, or via e
mail at ismpinfo@ismp.org. ISMP guarantees the confidentiality and security of
the information received and respects reporters' wishes as to the level of detail
included in publications.
PMID- 28515502
TI - ISMP Adverse Drug Reactions: Pregabalin-Induced Stuttering Nitroglycerine-Induced
Bradycardia Progressing to Asystole Minocycline-Induced DRESS Leading to Liver
Transplantation and Type 1 Diabetes Increased Risk of Vertebral Fractures in
Women Receiving Thiazide or Loop Diuretics Gambling Disorder and Impulse Control
Disorder with Aripiprazole.
AB - The purpose of this feature is to heighten awareness of specific adverse drug
reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to
the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If
you have reported an interesting, preventable ADR to MedWatch, please consider
sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside
Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail:
mmancano@temple.edu). Your report will be published anonymously unless otherwise
requested. This feature is provided by the Institute for Safe Medication
Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple
University School of Pharmacy. ISMP is an FDA MedWatch partner.
PMID- 28515503
TI - Drug Monographs: Olaratumab and Rucaparib.
AB - The complexity of cancer chemotherapy requires pharmacists be familiar with the
complicated regimens and highly toxic agents used. This column reviews various
issues related to preparation, dispensing, and administration of antineoplastic
therapy, and the agents, both commercially available and investigational, used to
treat malignant diseases. Questions or suggestions for topics should be addressed
to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc., 4201
Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J.
Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology
Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander
Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net. The information
presented in this review is based on published data and clinical expertise and
includes information not included in the product labeling. Incorporation of such
published data provides a more robust assessment of the drugs and assists
pharmacists in evaluation of orders for off-label use of these agents.
PMID- 28515504
TI - 21st Century Cures Act.
PMID- 28515505
TI - Application of the Layered Learning Practice Model in an Academic Medical Center.
AB - The layered learning practice model (LLPM) is a teaching strategy designed to
train residents to precept students and other residents with the oversight of a
seasoned clinical pharmacist. This model serves as a tool for residency programs
to implement quality precepting opportunities and learning experiences as they
look for new ways to integrate multiple learners into the practice setting. The
levels of the LLPM include a senior preceptor, resident, and student. It is best
implemented through utilization of 4 steps: orientation to the LLPM,
preexperience planning, implementation, and postexperience evaluation.
Orientation introduces preceptors and residents to the LLPM and outlines
expectations for each precepting level. Preexperience planning allows the
resident to take a leadership role in developing calendars, rotation activities,
rubrics, and activities that match goals and objectives. For implementation, the
senior preceptor maintains an active role with all learners; the resident serves
as the student's primary preceptor and is responsible for incorporating the
student into clinical activities, evaluating student work, and providing
feedback. Postexperience evaluation is designed to solicit and provide feedback
to the resident and student and to identify recommendations for improvement of
the LLPM. Overall, the LLPM is a multilayered model incorporating the expertise
and unique learning positions of the senior preceptor, resident, and student.
Redistributing components of the senior preceptor's responsibility amongst
learners may result in expansion of patient care and clinical services and help
satisfy the increasing demands placed on pharmacists.
PMID- 28515506
TI - Impact of Pharmacy Practice Model Expansion on Pharmacokinetic Services:
Optimization of Vancomycin Dosing and Improved Patient Safety.
AB - Background: The impact of pharmacy interventions on optimizing vancomycin therapy
has been described, however interventions vary among studies and the most optimal
pharmacy practice model (PPM) for pharmacokinetic (PK) services has not been
established. Objective: The purpose of this study is to demonstrate the value of
24 hours a day, 7 days a week (24/7) PK services. Methods: New PK services were
implemented in 2 phases with institutional PPM expansion. Phase 1 included
universal monitoring by pharmacists with recommendations made to prescribers
during business hours. Phase 2 expanded clinical pharmacists' coverage to 24/7
and provided an optional 24/7 pharmacist-managed PK consult service. We compared
vancomycin therapeutic trough attainment, dosing, and clinical and safety
outcomes between phases 1 and 2 in adult inpatients receiving therapeutic
intravenous vancomycin. Results. One hundred and fifty patients were included in
each phase. Phase 2 had a greater proportion of vancomycin courses with
therapeutic initial trough concentrations (27.5% vs 46.1%; p = 0.002), higher
initial trough concentrations (10.9 mcg/mL vs 16.4 mcg/mL; p < 0.001), and
optimized initial vancomycin dosing (13.5 mg/kg vs 16.2 mg/kg; p < 0.001). Phase
2 also saw significant reduction in the incidence of vancomycin-associated
nephrotoxicity (21.1% vs 11.7%; p = 0.038). Dose optimization and improvement in
initial target trough attainment were most notable among intensive care unit
(ICU) patients. Conclusions. Our study demonstrated that 24/7 PK services
implemented with institutional PPM expansion optimized vancomycin target trough
attainment and improved patient safety.
PMID- 28515507
TI - Implementing a Tech-Check-Tech Program at a University Health System.
AB - Background: Tech-Check-Tech (TCT) allows a pharmacy technician to perform the
final check of medications prepared by another technician. The effect of a TCT
program on the time required to process medications in a hospital pharmacy has
not been previously reported. Objective: To evaluate the effect of implementing a
TCT program on the time required to prepare, check, and deliver medications to
automated medication supply systems (AMSS) located throughout an academic medical
center. Methods: The primary outcome was the difference in mean total time
required to process AMSS medications between pre- and post-implementation
periods. Forty-five days pre-TCT implementation was compared to 45 days post
implementation. To assess the effect of the TCT program on pharmacist-time
allocation, median times required to verify stat and routine medication orders in
the computerized physician order entry (CPOE) system were analyzed. Results: Mean
total time spent processing AMSS medications was 24.16 +/- 2.98 hours and 16.79
+/- 2.65 hours for the pre- and post-TCT implementation periods, respectively
(difference of 7.37 hours; 95% CI, 6.19-8.55 hours; p < 0.0001). Median
verification times for stat medication orders were 5 (interquartile range [IQR],
2-12) minutes before and 4 (IQR, 2-9) minutes after TCT implementation (p <
0.0001). For routine orders, median verification times were 12 (IQR, 4-30)
minutes before and 7 (IQR, 3-18) minutes after implementation (p < 0.0001).
Conclusions: The total time required to process AMSS medications was
significantly reduced after a TCT program was implemented in an academic medical
center. Pharmacist medication order verification times were also significantly
reduced.
PMID- 28515508
TI - Evaluating Sterility of Single Dose Vials on an Automated Compounding Device.
AB - Background: Current guidelines for sterile compounding require that single dose
vials of pharmaceuticals must be discarded after 6 hours when accessed in an ISO
Class 5 environment. At this time, no studies have evaluated the sterility of
single dose vials at any time after opening. Objective: The purpose of this study
is to evaluate the sterility of single dose vials attached to an automated
compounding device for up to 24 hours and accessed and maintained within a
cleanroom environment. Methods: This is a prospective, observational study
evaluating the sterility of 32 pooled samples of manufactured single dose
injectable drugs attached to an automated compounding device for up to 24 hours
and maintained within an ISO Class 5 environment in an ISO Class 7 buffer area.
Each pooled sample was comprised of the remaining contents of 10 single dose vial
additives that were used for total parenteral nutrition (TPN) and attached to the
compounder within the previous 24 hours. Samples were evaluated using membrane
filtration sterility testing and incubated for 14 days per USP <71> requirements.
Results: The results revealed zero failed sterility samples. Single dose vials
remained attached to the compounder for an average of 23.8 hours (+/-0.1 hours).
The average volume per sample was 879 mL (+/-105.1 mL). Manipulation of vials
during the compounding process included an average of 20.4 manipulations (+/
1.4). Conclusions: Single dose injectable drugs attached to an automated
compounding device within an ISO Class 5 cleanroom environment may remain sterile
for up to 24 hours. Future studies are needed with a larger sample size and under
continued dynamic working conditions to provide further evidence to extend the
beyond use date within USP <797>.
PMID- 28515510
TI - Eteplirsen.
AB - Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well
documented monographs on drugs that are newly released or are in late phase 3
trials. The monographs are targeted to Pharmacy & Therapeutics Committees.
Subscribers also receive monthly 1-page summary monographs on agents that are
useful for agendas and pharmacy/nursing in-services. A comprehensive target drug
utilization evaluation/medication use evaluation (DUE/MUE) is also provided each
month. With a subscription, the monographs are available online to subscribers.
Monographs can be customized to meet the needs of a facility. Through the
cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in
this column. For more information about The Formulary Monograph Service, contact
Wolters Kluwer customer service at 866-397-3433. The April 2017 monograph topics
are deflazacort, plecanatide, delafloxacin, oxymetazoline hydrochloride 1% cream,
and betrixaban. The DUE is on plecanatide.
PMID- 28515509
TI - Anti-Nuclear Cytoplasmic Antibody-Associated Vasculitis: A Probable Adverse
Effect of Sofosbuvir Treatment in Chronic Hepatitis C Patients.
AB - Background: Egypt has the largest hepatitis C virus (HCV) epidemic worldwide.
Sofosbuvir is an antiviral drug acting by inhibition of the HCV NS5B polymerase.
It has shown high efficacy in combination with several other drugs and has a low
reported rate of side effects. Objective: The aim of this prospective cohort
study was to assess the safety of sofosbuvir-based treatment regimens used to
treat chronic hepatitis C infections and to detect any side effects of sofosbuvir
not previously reported. Methods: We studied treatment side effects in 3,000
patients with chronic HCV infection treated with sofosbuvir and ribavirin for 24
weeks or treated by pegylated interferon, sofosbuvir, and ribavirin triple
therapy for 12 weeks. The endpoint of the study was the end of treatment.
Results: Hyperbilirubinemia occurred frequently during treatment in both groups.
Treatment was discontinued in 72 cases due to hepatic decompensation and drug
complications; 8 of the cases had deep vein thrombosis (DVT) and 7 had cerebral
ischemia. Surprisingly, 177/3,000 (5.9%) patients presented with abnormal
bleeding, 85 of whom had a vasculitic skin rash. Conclusion: We report the
occurrence of previously nonrecorded side effects with sofosbuvir, namely DVT and
bleeding disorders associated with anti-nuclear cytoplasmic antibody (ANCA)
associated vasculitis (AAV).We believe this to be the first report of sofosbuvir
induced AAV skin lesions and bleeding disorders.
PMID- 28515511
TI - Approvals, Submission, and Important Labeling Changes for US Marketed
Pharmaceuticals.
AB - This monthly feature will help readers keep current on new drug, new indications,
dosage forms and safety-related changes in labeling or use. Efforts have been
made to assure the accuracy of this information; however, if there are any
questions, please let us know at jgeneral@ku.edu.
PMID- 28515513
TI - Hospital Participation in Prescription Drug Monitoring Programs.
AB - The prescription drug abuse epidemic continues to grow. This multifaceted problem
requires a multifaceted solution. In this installment, we discuss prescription
drug monitoring programs and their relevance to hospital pharmacies.
PMID- 28515512
TI - A Just Culture Approach to Managing Medication Errors.
AB - Medication errors continue to be a concern of health care providers and the
public, in particular how to prevent harm from medication mistakes. Many health
care workers are afraid to report errors for fear of retribution including the
loss of professional licensure and even imprisonment. Most health care workers
are silent, instead of admitting their mistake and discussing it openly with
peers. This can result in further patient harm if the system causing the mistake
is not identified and fixed; thus self-denial may have a negative impact on
patient care outcomes. As a result, pharmacy leaders, in collaboration with
others, must put systems in place that serve to prevent medication errors while
promoting a "Just Culture" way of managing performance and outcomes. This culture
must exist across disciplines and departments. Pharmacy leaders need to
understand how to classify behaviors associated with errors, set realistic
expectations, instill values for staff, and promote accountability within the
workplace. This article reviews the concept of Just Culture and provides ways
that pharmacy directors can use this concept to manage the degree of error in
patient-centered pharmacy services.
PMID- 28515514
TI - 'Advances in understanding and management in obstetric anaesthesia': The great
myth of our times.
PMID- 28515515
TI - The parturient in the interventional radiology suite: New frontier in obstetric
anaesthesia.
AB - The anaesthesiologist's presence during interventional radiology (IR) is
increasing due to increasingly ill patients and intricate procedures. The
management of a parturient in IR suite is complex in terms of logistics of an
unfamiliar procedure in an unfamiliar area. The literature available is largely
written by radiologists with little attention paid to anaesthetic details and
considerations. In the Indian scenario, in the absence of hybrid operating rooms
(ORs), logistics involve transport of a parturient back and forth between the IR
suite and the OR. As members of a multidisciplinary team, anaesthesiologists
should utilise their expertise in fluid management, transfusion therapy and
critical care to prevent and treat catastrophic events that may accompany severe
peri-partum bleeding. Ensuring familiarity with the variety of IR procedures and
the peri-procedure requirements can help the anaesthesiologist provide optimum
care in the IR suite.
PMID- 28515516
TI - Changes in cardiac index during labour analgesia: A double-blind randomised
controlled trial of epidural versus combined spinal epidural analgesia - A
preliminary study.
AB - BACKGROUND AND AIMS: Combined spinal-epidural (CSE) analgesia for labour and
delivery is occasionally associated with foetal bradycardia. Decreases in cardiac
index (CI) and/or uterine hypertonia are implicated as possible aetiological
factors. No study has evaluated CI changes following combined spinal analgesia
for labour and delivery. This prospective, double-blind, randomised controlled
trial evaluates haemodynamic trends during CSE and epidural analgesia for labour.
METHODS: Twenty-six parturients at term requesting labour analgesia were
randomised to receive either epidural (E) or CSE analgesia. The Electrical
Cardiometry Monitor ICON(r) was used to continuously determine maternal CI non
invasively, heart rate (HR) and stroke volume at baseline and up to 60 min after
initiation of either intrathecal or epidural analgesia. In addition, maternal
systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded.
RESULTS: Both SBP and DBP had a similar, significant decrease following
initiation of either epidural or CSE analgesia. However, parturients in the CSE
group (n = 10) demonstrated a significant decrease in HR and CI compared to the
baseline measurements. On the other hand, the parturients in the E (n = 13) group
showed no decreases in either maternal HR or CI. Foetal heart changes were
observed in four patients following CSE and one patient following an epidural.
CONCLUSION: Labour analgesia with CSE is associated with a significant decrease
in HR and CI when compared to labour analgesia with epidural analgesia. Further
studies are necessary to determine whether a decrease in CI diminishes placental
blood flow.
PMID- 28515517
TI - A clinical comparison between 0.5% levobupivacaine and 0.5% levobupivacaine with
dexamethasone 8 mg combination in brachial plexus block by the supraclavicular
approach.
AB - BACKGROUND AND AIMS: Dexamethasone as an adjuvant to bupivacaine for
supraclavicular brachial plexus (SCBP) block prolongs motor and sensory blockade.
However, the effect of dexamethasone (8 mg) when added to levobupivacaine has not
been well studied. This study was conducted to find out analgesic efficacy of
dexamethasone as adjuvant to levobupivacaine in SCBP block. METHODS: Ultrasound-
guided SCBP block was given to sixty patients, randomly assigned into two groups.
Group S (thirty patients) received 2 mL normal saline with 25 mL levobupivacaine
(0.5%) and Group D (thirty patients) received 2 mL of dexamethasone (8 mg) with
25 mL of levobupivacaine (0.5%), respectively. Time for the first rescue
analgesia, number of rescue analgesics required in 24 h and different block
characteristics was assessed. Chi-square test and Student's t-test were used for
statistical analysis. RESULTS: Time for request of the first rescue analgesia was
396.13 +/- 109.42 min in Group S and 705.80 +/- 121.46 min in Group D (P <
0.001). The requirement for rescue analgesics was more in Group S when compared
to Group D. The onset of sensory and motor block was faster in Group D when
compared to Group S. The mean duration of sensory and motor block was
significantly longer in Group D than Group S. CONCLUSION: The addition of
dexamethasone to levobupivacaine in SCBP blockade prolonged time for first rescue
analgesia and reduced the requirement of rescue analgesics with faster onset and
prolonged duration of sensory and motor block.
PMID- 28515519
TI - Desflurane for ambulatory anaesthesia: A comparison with sevoflurane for recovery
profile and airway responses.
AB - BACKGROUND AND AIMS: Desflurane and sevoflurane have low blood gas solubility co
efficients, allowing a rapid awakening from anaesthesia. However, desfluraneis
pungent and may cause airway irritability. We compared desflurane and sevoflurane
with respect to recovery and occurrence of adverse airway responses in
spontaneously breathing patients while using the ProSealTM laryngeal mask airway
(LMA). METHODS: Ninety-four adult patients undergoing hysteroscopic procedures
were divided into sevoflurane (S) group or desflurane (D) group. Patients were
premedicated with midazolam 0.03 mg/kg and fentanyl 1MUg/kg. Anaesthesia was
induced with propofol 2.0-2.5 mg/kg, followed by insertion of a ProSealTM LMA.
Adverse airway responses such as cough, hiccups, laryngospasm and breathholding
were recorded. In the post-operative period: time to awakening, response to
verbal commands, orientation, ability to sit with support and the recovery room
Aldrete score were recorded. RESULTS: Three patients in group S (6.4%) and six
patients (13.3%) in Group D had adverse airway events. The mean time to eye
opening (Group S-10.75 +/- 7.54 min, Group D-4.94 +/- 1.74 min), obeying verbal
commands (Group S-13.13 +/- 8.75 min, Group D-6.55 +/- 1.75 min), orientation
(Group S-15.42 +/- 8.46 min, Group D-6.23 +/- 2.4 min) and to sit with support
(Group S-36.09 +/- 12.68 min, Group D-14.35 +/- 3.75 min) were found to be lesser
with desflurane than with sevoflurane (P < 0.001). The mean time to recovery was
delayed in Group S-46.00 +/- 12.86 min compared to Group D-26.44 +/- 5.33 min (P
< 0.001). CONCLUSION: Desflurane has faster awakening properties than sevoflurane
without an increase in adverse airway events when used during spontaneous
ventilation through a ProSealTM LMA along with propofol and fentanyl.
PMID- 28515518
TI - Is segmental epidural anaesthesia an optimal technique for patients undergoing
percutaneous nephrolithotomy?
AB - BACKGROUND AND AIMS: Neuraxial anaesthesia has recently become popular for
percutaneous nephrolithotomy (PCNL). We conducted a study comparing general
anaesthesia (GA) with segmental (T6-T12) epidural anaesthesia (SEA) for PCNL with
respect to anaesthesia and surgical characteristics. METHODS: Ninety American
Society of Anesthesiologists Physical Status-I and II patients undergoing PCNL
randomly received either GA or SEA. Overall patient satisfaction was the primary
end point. Intraoperative haemodynamics, epidural block characteristics, post
operative pain, time to rescue analgesic, total analgesic consumption, discharge
times from post-anaesthesia care unit, surgeon satisfaction scores and stone
clearance were secondary end points. Parametric data were analysed by Student's t
test while non-parametric data were compared with Mann-Whitney U-test. RESULTS:
Group SEA reported better patient satisfaction (P = 0.005). Patients in group GA
had significantly higher heart rates (P = 0.0001) and comparable mean arterial
pressures (P = 0.24). Postoperatively, time to first rescue analgesic and total
tramadol consumption was higher in Group GA (P = 0.001). Group SEA had lower pain
scores (P = 0.001). Time to reach Aldrete's score of 9 was shorter in group SEA
(P = 0.0001). The incidence of nausea was higher in group GA (P = 0.001);
vomiting rates were comparable (P = 0.15). One patient in group SEA developed
bradycardia which was successfully treated. Eight patients (18%) had hypertensive
episodes in group GA versus none in group SEA (P = 0.0001). One patient in GA
group had pleural injury and was managed with intercostal drain. Stone clearance
and post-operative haemoglobin levels were comparable in both groups. CONCLUSION:
PCNL under SEA has a role in selected patients, for short duration surgery and in
expert hands.
PMID- 28515520
TI - A comparative evaluation of Video Stylet and flexible fibre-optic bronchoscope in
the performance of intubation in adult patients.
AB - BACKGROUND AND AIMS: Video Stylet (VS) is a new intubating modality that provides
real-time video of endotracheal intubation (ETI). This device does not need
alignment of the oral, pharyngeal and tracheal axes to view glottis and can be
used in patients with limited mouth opening. The aim of this study was to compare
flexible fibre-optic (FO) bronchoscope with VS in elective surgical patients in
apparently normal airway patients requiring oral ETI. METHODS: Sixty patients
undergoing elective surgery under general anaesthesia of age group 20-60 years,
weight 40-70 kg, American Society of Anesthesiologist 1 and 2 and modified
Mallampatti I and II were included in the study. Patients in group FO (n = 30)
were intubated by flexible FO bronchoscope, whereas patients in group VS (n = 30)
were intubated by VS. Primary outcome measure was time taken for intubation
(TTI). Secondary outcome measures were successful intubation, haemodynamic
response and post-operative complications if any. RESULTS: Average TTI in cases
of FO group was 38.2 s (95% confidence interval [CI] 36-41) and in VS group was
19.7 s (95% CI 19-21; P = 0.0001). Three patients required a second attempt for
successful intubation in FO group compared to eight in VS group (P = 0.2), with
no failures in any group. Haemodynamic response and complications rate were
greater in VS group; however, the differences were not statistically significant.
CONCLUSION: VS takes lesser time to intubate than flexible FO bronchoscope.
PMID- 28515522
TI - Comparison of AirtraqTM, McCoyTM and Macintosh laryngoscopes for endotracheal
intubation in patients with cervical spine immobilisation: A randomised clinical
trial.
AB - BACKGROUND AND AIMS: The study aimed at comparing the performance of the novel
optical AirtraqTM laryngoscope with the McCoyTM and conventional Macintosh
laryngoscopes for ease of endotracheal intubation in patients with neck
immobilisation using manual inline axial cervical spine stabilisation (MIAS)
technique. METHODS: Ninety consenting American Society of Anaesthesiologist's
physical status I-II patients, aged 18-60 years, scheduled for various surgeries
requiring tracheal intubation were randomly assigned into three groups of thirty
each to undergo intubation with Macintosh, AirtraqTM, or McCoyTM laryngoscope
with neck immobilisation by MIAS technique. The ease of intubation based on
Intubation difficulty scale (IDS) score, Cormack-Lehane grade of glottic view,
optimisation manoeuvres and impact on haemodynamic parameters were recorded.
Statistical analysis was performed with ANOVA and Bonferroni correction for post
hoc tests. RESULTS: All patients in three groups had a comparable demographic
profile and were successfully intubated. The AirtraqTM laryngoscope significantly
reduced the IDS (mean - 0.43 +/- 0.81) as compared with both McCoyTM (mean - 1.63
+/- 1.49, P = 0.001) and Macintosh laryngoscope (mean -2.23 +/- 1.92, P < 0.001)
and improved the Cormack-Lehane glottic view (77% grade 1 view and no patients
with grade 3 or 4 view). There were less haemodynamic variations during
laryngoscopy with the AirtraqTM compared to the Macintosh laryngoscope, but there
was not between the AirtraqTM and McCoyTM laryngoscope groups. CONCLUSION: In
patients undergoing endotracheal intubation with cervical immobilisation,
AirtraqTM laryngoscope was superior to the McCoyTM and Macintosh laryngoscopes,
with greater ease of intubation and lower impact on haemodynamic variables.
PMID- 28515521
TI - Comparative evaluation of AirtraqTM optical Laryngoscope and Miller's blade in
paediatric patients undergoing elective surgery requiring tracheal intubation: A
randomized, controlled trial.
AB - BACKGROUND AND AIMS: The AirtraqTM optical laryngoscope is the only marketed
videolaryngoscope for paediatric patients besides the fibre-optic bronchoscope.
We hypothesized that intubation would be easier with AirtraqTM compared to Miller
blade. Hence, we compared AirtraqTM with the Miller laryngoscope as intubation
devices in paediatric patients. METHODS: This prospective, randomized study was
conducted in a tertiary care teaching hospital. Sixty children belonging to
American Society of Anesthesiologists' Grade I-II, aged 2-10 years, posted for
routine surgery requiring tracheal intubation were randomly allocated to undergo
intubation using a Miller (n = 30) or AirtraqTM (n = 30) laryngoscope. The
primary outcome measure was time of intubation. We also measured ease of
intubation, number of attempts, percentage of glottic opening score (POGO),
haemodynamic changes and airway trauma. Student t test was used to analyse
parametric data. RESULTS: Intubation time was comparable between Miller's
laryngoscope (15.13 +/- 1.33s) compared to AirtraqTM (11.53 +/- 0.49 s) (P =
0.29) The number of first and second attempts at intubation were 25 and 5 for the
Miller laryngoscope and 29 and 1 for the AirtraqTM. Median visual analogue score
(VAS) for ease of intubation was 5 in Miller group compared to 3 in AirtraqTM
group. The median POGO score was 75 in the Miller group and 100 in the AirtraqTM
group (P = 0.01). Haemodynamic changes were maximum and most significant
immediately and 1 min after intubation. Airway trauma occurred in three patients
(9.09%) in Miller group and one patient (3.33%) in AirtraqTM group. CONCLUSION:
The AirtraqTM reduced the difficulty of tracheal intubation and degree of
haemodynamic stimulation compared to the Miller laryngoscope in paediatric
patients.
PMID- 28515523
TI - Comparison of endotracheal intubation time in neutral position between C-Mac(r)
and Airtraq(r) laryngoscopes: A prospective randomised study.
AB - BACKGROUND AND AIMS: In the recent past, many novel devices such as AirTraq(r)
and C-MAC(r) video laryngoscope (VL) have been introduced in an attempt to reduce
anaesthetic morbidity and mortality associated with difficult intubation. In this
study, we aimed to evaluate and compare C-MAC(r) VL with a standard Macintosh
blade and the AirTraq(r) optical laryngoscope as a intubating devices with the
patient's head in neutral position. METHODS: Sixty American Society of
Anesthesiologist Physical Status I-II patients were randomly assigned to be
intubated with C-MAC(r) VL (Group CM; n = 30) or AirTraq(r) (Group AT; n = 30) in
the neutral position, with or without the application of optimization manoeuvres.
The primary outcomes of this study were the success rate and the time taken to
intubate. Glottic view, ease of tracheal intubation and haemodynamic responses
were considered as secondary end points. RESULTS: The incidence of successful
intubation was similar in both the groups (P = 1.00). However, the time for
intubation was significantly less with C-MAC(r) VL (Group CM = 14.9 +/- 12.89 s,
Group AT = 26.3 +/- 13.34 s; P = 0.0014). There was no significant difference
between the two groups in terms of ease of intubation and glottic view. However,
the haemodynamic perturbations were much less with C-MAC(r) VL. CONCLUSION: We
conclude that both the devices were similar in visualising larynx in the neutral
position with similar success rates of intubation. However, the C-MAC(r) VL was
better with respect to intubation time and haemodynamic stability.
PMID- 28515524
TI - Spinal anaesthesia for a caesarean section in a patient with paraneoplastic
cerebellar ataxia.
AB - Paraneoplastic cerebellar ataxia (PCA) is most frequently observed in
gynaecological cancers, small cell lung cancer, breast cancer, Hodgkin's
lymphoma, cancer testis or malignant thymoma. In the literature, there is no data
related to the effects of PCA during pregnancy or reports on the effects of
anaesthesia in patients with PCA. We present management of a pregnant woman with
PCA who was suddenly unable to walk with PCA and for whom effective spinal
anaesthesia was performed for an elective caesarean section with no
complications.
PMID- 28515525
TI - Management of an intraoperatively damaged endotracheal tube in a case of
difficult airway using fibre-optic bronchoscope with minimal apnoea period.
AB - Damage to the endotracheal tube (ETT) is common in head and neck surgeries,
especially in maxillary osteotomy. Airway management in such a crisis is crucial
as there is risk of aspiration of blood into lungs, hypoxia and apnoea. This case
illustrates a patient with an anticipated difficult airway who had an
intraoperative damage to the ETT and was successfully managed by re-intubation
with fiberoptic bronchoscope in a minimal apnoea period of <15 s using a new
technique.
PMID- 28515526
TI - Fentanyl or ketamine pre-treatment to prevent withdrawal response to rocuronium.
PMID- 28515527
TI - Can fluid resuscitation be a risk factor for laryngeal oedema in severe dengue?
PMID- 28515528
TI - Perioperative management of a patient with haemophilia-A for major abdominal
surgery.
PMID- 28515529
TI - Failing to learn from the past: Report of a patient with twice failed central
venous cannulation.
PMID- 28515531
TI - Anaesthetic management of a pregnant woman with preeclampsia and Eisenmenger's
syndrome: Role of advanced haemodynamic monitoring.
PMID- 28515530
TI - Maternal patent ductus arteriosus with bidirectional shunt: Obstetric anaesthesia
and its challenges.
PMID- 28515532
TI - Asystole during rigid bronchoscopic stenting under general anaesthesia in a
patient with tracheo-oesophageal fistula.
PMID- 28515533
TI - Bilateral quadratus lumborum block for post-caesarean analgesia.
PMID- 28515534
TI - Quadratus lumborum block for post-caesarean analgesia.
PMID- 28515536
TI - Estimation of the linear mixed integrated Ornstein-Uhlenbeck model.
AB - The linear mixed model with an added integrated Ornstein-Uhlenbeck (IOU) process
(linear mixed IOU model) allows for serial correlation and estimation of the
degree of derivative tracking. It is rarely used, partly due to the lack of
available software. We implemented the linear mixed IOU model in Stata and using
simulations we assessed the feasibility of fitting the model by restricted
maximum likelihood when applied to balanced and unbalanced data. We compared
different (1) optimization algorithms, (2) parameterizations of the IOU process,
(3) data structures and (4) random-effects structures. Fitting the model was
practical and feasible when applied to large and moderately sized balanced
datasets (20,000 and 500 observations), and large unbalanced datasets with (non
informative) dropout and intermittent missingness. Analysis of a real dataset
showed that the linear mixed IOU model was a better fit to the data than the
standard linear mixed model (i.e. independent within-subject errors with constant
variance).
PMID- 28515537
TI - Estimating spatially distributed turbulent heat fluxes from high-resolution
thermal imagery acquired with a UAV system.
AB - In this study, high-resolution thermal imagery acquired with a small unmanned
aerial vehicle (UAV) is used to map evapotranspiration (ET) at a grassland site
in Luxembourg. The land surface temperature (LST) information from the thermal
imagery is the key input to a one-source and two-source energy balance model.
While the one-source model treats the surface as a single uniform layer, the two
source model partitions the surface temperature and fluxes into soil and
vegetation components. It thus explicitly accounts for the different
contributions of both components to surface temperature as well as turbulent flux
exchange with the atmosphere. Contrary to the two-source model, the one-source
model requires an empirical adjustment parameter in order to account for the
effect of the two components. Turbulent heat flux estimates of both modelling
approaches are compared to eddy covariance (EC) measurements using the high
resolution input imagery UAVs provide. In this comparison, the effect of
different methods for energy balance closure of the EC data on the agreement
between modelled and measured fluxes is also analysed. Additionally, the
sensitivity of the one-source model to the derivation of the empirical adjustment
parameter is tested. Due to the very dry and hot conditions during the
experiment, pronounced thermal patterns developed over the grassland site. These
patterns result in spatially variable turbulent heat fluxes. The model comparison
indicates that both models are able to derive ET estimates that compare well with
EC measurements under these conditions. However, the two-source model, with a
more complex treatment of the energy and surface temperature partitioning between
the soil and vegetation, outperformed the simpler one-source model in estimating
sensible and latent heat fluxes. This is consistent with findings from prior
studies. For the one-source model, a time-variant expression of the adjustment
parameter (to account for the difference between aerodynamic and radiometric
temperature) that depends on the surface-to-air temperature gradient yielded the
best agreement with EC measurements. This study showed that the applied UAV
system equipped with a dual-camera set-up allows for the acquisition of thermal
imagery with high spatial and temporal resolution that illustrates the small
scale heterogeneity of thermal surface properties. The UAV-based thermal imagery
therefore provides the means for analysing patterns of LST and other surface
properties with a high level of detail that cannot be obtained by traditional
remote sensing methods.
PMID- 28515538
TI - Effects of Engaging in Repeated Mental Imagery of Future Positive Events on
Behavioural Activation in Individuals with Major Depressive Disorder.
AB - Depression is associated with decreased engagement in behavioural activities. A
wide range of activities can be promoted by simulating them via mental imagery.
Mental imagery of positive events could thus provide a route to increasing
adaptive behaviour in depression. The current study tested whether repeated
engagement in positive mental imagery led to increases in behavioural activation
in participants with depression, using data from a randomized controlled trial
(Blackwell et al. in Clin Psychol Sci 3(1):91-111, 2015.
doi:10.1177/2167702614560746). Participants (N = 150) were randomized to a 4-week
positive imagery intervention or an active non-imagery control condition,
completed via the internet. Behavioural activation was assessed five times up to
6 months follow-up using the Behavioural Activation for Depression Scale (BADS).
While BADS scores increased over time in both groups, there was an initial
greater increase in the imagery condition. Investigating mental imagery
simulation of positive activities as a means to promote behavioural activation in
depression could provide a fruitful line of enquiry for future research.
PMID- 28515539
TI - Why Does Positive Mental Health Buffer Against Psychopathology? An Exploratory
Study on Self-Compassion as a Resilience Mechanism and Adaptive Emotion
Regulation Strategy.
AB - Growing evidence suggests that positive mental health or wellbeing protects
against psychopathology. How and why those who flourish derive these resilient
outcomes is, however, unknown. This exploratory study investigated if self
compassion, as it continuously provides a friendly, accepting and situational
context for negative experiences, functions as a resilience mechanism and
adaptive emotion regulation strategy that protects against psychopathology for
those with high levels of positive mental health. Participants from the general
population (n = 349) provided measures at one time-point on positive mental
health (MHC-SF), self-compassion (SCS-SF), psychopathology (HADS) and negative
affect (mDES). Self-compassion significantly mediated the negative relationship
between positive mental health and psychopathology. Furthermore, higher levels of
self-compassion attenuated the relationship between state negative affect and
psychopathology. Findings suggest that especially individuals with high levels of
positive mental health possess self-compassion skills that promote resilience
against psychopathology. These might function as an adaptive emotion regulation
strategy and protect against the activation of schema related to psychopathology
following state negative affective experiences. Enhancing self-compassion is a
promising positive intervention for clinical practice. It will not only impact
psychopathology through reducing factors like rumination and self-criticism, but
also improve positive mental health by enhancing factors such as kindness and
positive emotions. This may reduce the future risk of psychopathology.
PMID- 28515540
TI - Opportunities and Challenges for the Emerging Field of Positive Emotion
Regulation: A Commentary on the Special Edition on Positive Emotions and
Cognitions in Clinical Psychology.
AB - The importance of developing a better understanding of positive emotion
regulation in both healthy and clinical populations is now recognised. This
special edition brings together leading figures in the positive emotion
regulation field and has contributions characterizing positive phenomena,
differentiating them from negative phenomena, and evaluating underlying
psychological mechanisms that drive these phenomena. This commentary reviews
these articles to highlight challenges and opportunities for this emerging field,
including the need to better characterize positive phenomena, to be more explicit
about how the links between negative and positive phenomena are conceptualised,
to evaluate more robustly underlying mechanisms, to standardize measurement of
positive constructs, and to ensure that these scientific findings lead to
meaningful changes in real-world policy and practice.
PMID- 28515541
TI - Automaticity of Attentional Bias to Threat in High and Low Worriers.
AB - Individuals with high levels of worry are more likely than others to attend to
possible threats, although the extent of top-down attentional control processes
on this bias is unknown. We compared the performance of high (n = 26) and low
worriers (n = 26) on a probe discrimination task designed to assess attention to
threat cues, under cognitive load or no-load conditions. The expected difference
between groups was confirmed, with high worriers being more likely to attend to
threat cues than low worriers. Importantly however, there were no significant
effects involving condition (cognitive load vs. no-load), nor any significant
association with self-perceived attentional control ability. These results
suggest that pathological worriers are more likely to attend to threat than are
individuals with low levels of worry, regardless of task demands on limited
cognitive control resources. This finding is consistent with the dominance of
habitual bottom-up influences over top-down control processes in biased attention
to threat.
PMID- 28515542
TI - The Role of Cognitive Factors in Childhood Social Anxiety: Social Threat Thoughts
and Social Skills Perception.
AB - Models of cognitive processing in anxiety disorders state that socially anxious
children display several distorted cognitive processes that maintain their
anxiety. The present study investigated the role of social threat thoughts and
social skills perception in relation to childhood trait and state social anxiety.
In total, 141 children varying in their levels of social anxiety performed a
short speech task in front of a camera and filled out self-reports about their
trait social anxiety, state anxiety, social skills perception and social threat
thoughts. Results showed that social threat thoughts mediated the relationship
between trait social anxiety and state anxiety after the speech task, even when
controlling for baseline state anxiety. Furthermore, we found that children with
higher trait anxiety and more social threat thoughts had a lower perception of
their social skills, but did not display a social skills deficit. These results
provide evidence for the applicability of the cognitive social anxiety model to
children.
PMID- 28515543
TI - Empirical Reality of Dialectical Behavioral Therapy in Borderline Personality.
PMID- 28515544
TI - The Importance of Cholesterol in Psychopathology: A Review of Recent
Contributions.
AB - AIM: The aim of this study was to describe systematically recent studies that
show the importance of cholesterol in psychopathology. METHODS: This study was a
review. The following databases were searched for relevant published articles on
human studies: MEDLINE, Web of Science, EBSCOhost Academic Search Complete, and
Psychology and Behavioral Sciences Collection (papers from January 2012 to March
2016). RESULTS: Eighteen recent papers were selected, and thematic dimensions
showing correlations between cholesterol and behavioral and psychopathological
variables were depression, suicide, personality, and aggression. CONCLUSION: This
paper demonstrates that recent research corroborates the idea that cholesterol
plays an important role in governing behavior and psychopathology in humans.
Deepening the studies in this field could be a promising avenue for future
research, with implications for treating people with behavior or mental health
problems.
PMID- 28515546
TI - Use of Jonkman et al. Score for Visual Quantification of Electroencephalography
as a Tool to Assess Disease Severity in Cortical Dementias.
AB - OBJECTIVES: To study electroencephalography (EEG) changes in patients with
cortical dementias (Alzheimer's disease [AD] and frontotemporal dementia (FTD).
(1) To correlate EEG changes with clinical severity of dementia as assessed by
rating scales. (2) To correlate global gray matter volume (GGMV) with EEG scores
and clinical severity rating scales. PATIENTS AND METHODS: This is a prospective
cross-sectional study involving patients fulfilling the criteria for Probable AD
and FTD. A total of thirty patients (20 = FTD, 10 = AD) underwent detailed
neuropsychological evaluation, dementia rating scales, EEG, and magnetic
resonance imaging. Five EEG parameters were acquired and each parameter is scaled
and the total score was compared with neuropsychological parameters and GGMV.
RESULTS: For FTD, the mean age of patients was 58.85 +/- 6.87, mean mini-mental
state examination score was 13.30 +/- 6.33, Hindi mental state examination: 14.35
+/- 6.28, mean grant total EEG score (GTES): 7.80 +/- 5.39, and mean GGMV:
464580.76 +/- 52127 mm3 and for AD, the same were 69.50 +/- 8.59, 12.90 +/- 5.56,
14.20 +/- 5.31, 9.80 +/- 5.29, and 483208 +/- 47371.5 mm3, respectively. GTES for
mild, moderate, and severe FTD are 2.33 +/- 1.528, 6.00 +/- 3.162, and 10.70 +/-
5.677 and for AD it is 4, 7.50 +/- 4.041, 15 +/- 1.414, respectively. The GGMV
for mild, moderate, and severe FTD was 511836 +/- 45005, 492693.1 +/- 50624, and
430725 +/- 30744 and for AD it is 527217.3 +/- 36171, 503598 +/- 3006, and 440812
+/- 33911. DISCUSSION: The most common EEG abnormalities in cortical dementias
are reduced frequency of rhythmic background activity. There is a significant
correlation between GTES and dementia severity and global gray matter volume but
the proportional correlation with GTES and volumetric scores is not significant.
CONCLUSION: EEG is a cheap and sensitive and easily available tool to assess
disease severity in patients with cortical dementias and thus helps in planning
the type of rehabilitatory interventions and prognostication.
PMID- 28515545
TI - Traumatic Brain Injury and Neuropsychiatric Complications.
AB - Traumatic brain injury (TBI) occurs when a blow or jolt to the head or a
penetrating injury results in damage to the brain. It is the most frequent cause
of hospitalization in young people with a higher prevalence in men. TBI is the
leading cause of disability and mortality between the ages 1 and 45. TBI can be
caused either by the direct result of trauma or due to a complication of the
primary injury. The most common etiological factors for TBI are falls, road
traffic accidents, violent physical assaults, and injuries associated with
athletic activities. Following TBI, significant neurologic complications may
occur which include seizures, dementia, Alzheimer's disease, and cranial nerve
injuries. In addition, people may suffer from various psychiatric complications
such as depression, posttraumatic stress disorder, generalized anxiety disorder,
obsessive-compulsive disorder, and other cognitive and behavioral sequel that
might significantly increase the comorbidity of the victims. Considering all of
the above complications, TBI is one of the significant public health burdens.
Literature has shown that only about 25% of people achieve long-term functional
independence following TBI. In this paper, we focused not only on the
epidemiology but also the etiology, complications following TBI and understanding
their underlying pathogenesis. Further, we focused on analyzing the options to
improve the treatment and rehabilitation following TBI in future.
PMID- 28515547
TI - A Randomized Pilot Study of Brief Intervention versus Simple Advice for Women
Tobacco Users in an Urban Community in India.
AB - AIM: The study aimed to assess the efficacy of providing brief intervention (BI)
for women tobacco users in a community-based setting. METHODS: In this open
labeled randomized study, a representative sample of women (n = 100) from a
community in East Delhi were screened using Alcohol, Smoking and Substance
Involvement Screening Test. Eligible women were randomized to BI or simple advice
(SA) arms. At baseline, they were assessed for tobacco use characteristics and
severity of nicotine dependence using Fagerstrom's test for nicotine dependence.
Intervention in the form of a single session of BI or SA to quit tobacco was
provided at baseline. All participants were assessed at 1 week and 3 months
following intervention. The principal outcome was self-reported abstinence from
tobacco use at 3 months follow-up. RESULTS: The mean age of the sample was 43
years (standard deviation = 13). Most women were married (80%), housewives (69%),
illiterate (61%), socioeconomically disadvantaged and were smokeless tobacco
users (94%). The subjects in the BI group were twice more likely to stop tobacco
use as compared to individuals in the SA group (odds ratio = 2.2, 95% confidence
interval: 0.962-5.197, P = 0.06). CONCLUSION: The study results are suggestive of
beneficial effect of BI. A larger study might provide more significant results.
PMID- 28515548
TI - Culturally Relevant Family Therapy Practice with Parents of Children and
Adolescents.
AB - BACKGROUND: India is diverse in culture, with multiple aspects that may not match
with the Western societal picture. Hence, it has often been seen that therapists
encounter unique aspects of therapy that is faced during actual practice, which
is never written in any textbook or research papers. Substantial information is
present through both outcome (efficacy and effectiveness) studies and process
research, but it has very little impact of actual Marital and Family Therapy
(MFT) practice. This paper throws light into "how" and "what" of family therapy
with parents of children/adolescents having psychiatric disorders. MATERIALS AND
METHODS: Focused group discussion was conducted with practicing family therapists
and mental health professionals working in Psychiatric Tertiary Hospital
(National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka,
India). Qualitative analysis was done to disseminate process issues in therapy.
RESULTS: Aspects that are vital for families having children and adolescent with
psychiatric disorders include: Academic decline and loss of parental control as
main reasons for seeking help, integration of models is noted to be beneficial,
therapeutic alliance, intake sessions, conjoint sessions and individual sessions
are important, cultural issues like gender of therapist, their cultural belief
model, therapist's cultural competence need to be taken into consideration.
CONCLUSIONS: Challenges and way-outs to overcome these has been mentioned and
implications discussed.
PMID- 28515549
TI - Evaluation of Modified Patient Health Questionnaire-9 Teen in South African
Adolescents.
AB - BACKGROUND: This report describes the findings of the survey conducted by South
African Depression and Anxiety Group (SADAG) in a cohort of disadvantaged South
African adolescent scholars in which PHQ-9 teen version was modified and adapted
(PHQ-9M) to improve the response rate. METHOD: PHQ-9M was administered to 2025
secondary students of 35 schools over 2 years in Gauteng Province, South Africa.
RESULTS: The mean age was 15.8 years. 23% of respondents scored 9 or above, 26.7%
reported suicidal ideations in last month, 21.8% reported lifetime suicide
attempts and 9.3% had severe functional impairment. PHQ-9M showed a fair internal
consistency and face validity in this study. CONCLUSION: The PHQ-9M could be
useful in conducting surveys in settings of low mental health literacy after
further evaluation of its psychometric properties. The high rates of suicidal
ideations, suicide attempts, and functional impairment in this population suggest
the need for preventive interventions.
PMID- 28515550
TI - Communication Impairments in Children with Inborn Errors of Metabolism: A
Preliminary Study.
AB - PURPOSE: Inborn Errors of Metabolism (IEMs) are a group of complex genetic
conditions, predominantly affecting the pediatric population. While the
understanding and identification of various IEMs has significantly improved over
recent times, not much is known about the communication disorders in this
population. The present study focused on identification and profiling of
communication impairments in children diagnosed with IEMs. METHODS: Data was
obtained retrospectively from medical records of children visiting a tertiary
care hospital over a period of ten years (2005 - 2014). Selected data was
reviewed to obtain demographic details, clinical signs/manifestations, laboratory
findings, risk factors, developmental disorders and reported communication
impairments. RESULTS: The findings of the study showed a variety of clinical
signs and laboratory findings in children with inborn errors of metabolism. A few
of the risk factors observed in the group were consanguinity, sibling death and
family history of other disorders. Many children with IEM displayed communication
disorders, most common as the delay in speech and language development.
CONCLUSIONS: The results of this study showed that various communication
disorders were seen in almost half of the children with a diagnosis of IEM.
Findings are discussed with implications for future research in this direction.
PMID- 28515551
TI - Combining Metacognitive Strategies with Traditional Cognitive Behavior Therapy in
Generalized Anxiety Disorder: A Case Illustration.
AB - CONTEXT: Generalized anxiety disorder (GAD) is a challenging clinical condition
to manage. Recent psychological models of GAD emphasis on the need to focus on
metacognitive processes in addition to symptom reduction. AIMS: We examined the
application of metacognitive strategies in addition to conventional cognitive
behaviour therapy (CBT) techniques in an adult patient with GAD. SETTINGS AND
DESIGNS: Asingle case design with pre- and post-assessments on clinician-rated
scales was adopted. MATERIALS AND METHODS: Twelve weekly sessions of therapy were
conducted on an outpatient basis. Assessments were carried out on clinical global
impressions scales, Hamilton's anxiety rating scale at pre- and post-therapy
points. STATISTICAL ANALYSIS: Pre- and post-therapy changes were examined using
the method of clinical significance. RESULTS: A combination of traditional CBT
with MCT was effective in addressing anxiety and worry in this patient with GAD.
The case illustrates the feasibility of matching therapeutic strategies to
patient's symptom list and demonstrates a blend of metacognitive strategies and
conventional CBT strategies. CONCLUSIONS: In clinical practice, matching
strategies to patient's problem list is important to be an effective approach.
PMID- 28515553
TI - Long Loop Reflex 2 in Patients with Cortical Dementias: A Pilot Study.
AB - INTRODUCTION: Dementia is a major public health problem and it appears to be a
global epidemic. The prevalence is doubling every 5 years and it is expected that
70% of persons above 60 years will live in developing countries by 2020 and 15%
of them are likely to suffer from dementia. Disease modifying treatments work
only if initiated very early; however, diagnostic tools are not always able to
clearly differentiate the different types in very early stage. Therefore,
inexpensive and easily available biomarkers are needed to know if collectively
they will improve the sensitivity of specific diagnosis. Therefore, in this pilot
study, we have tried to analyze if long loop reflex (LLR2) is differentially
affected in these two conditions early in the course of Alzheimer's dementia (AD)
and frontotemporal dementia (FTD) based on hypothesis taking into account the
anatomical substrates involved. PATIENTS AND METHODS: Mild cases of clinically
probable AD and FTD after appropriate inclusion criteria were subjected for LLR
testing in the upper limb at median nerve. The presence or absence of LLR was
assessed and also the latency, amplitude, and duration assessed. RESULTS AND
CONCLUSION: LLR 2 is differentially affected in both these conditions. Absence of
LLR2 was consistently seen in FTD which can be explained by early break down of
frontal subcortical circuits in this condition as against AD. This is likely to
serve as a very cheap and very early biomarker to differentiate the two common
types of cortical dementias.
PMID- 28515552
TI - The Influence of Psychosocial Dysfunctions in Chronic Schizophrenia Patients in
Remission: A Hospital-Based Study.
AB - BACKGROUND: Psychosocial dysfunctions in the various psychosocial areas in
chronic schizophrenic patients predict the long-term course, outcome, and quality
of life of these patients, which always varies with years of treatment.
OBJECTIVE: To know the influence and compare the level of psychosocial
dysfunctions and severity of disability burden in chronic schizophrenic patients
who are in remission with duration of 5 and 20 years. MATERIALS AND METHODS: The
sample was collected from the OPD of Mental Health Institute (COE), S.C.B.
Medical College, Cuttack, Odisha, India. This study is a cross-sectional study. A
total of 120 remitted schizophrenic patients (60 patients of each group with
duration of 5 and 20 years), who fulfilled Nancy Andreasen criteria for Remission
were selected for the study. Regional language of dysfunction analysis
questionnaire (DAQ) was used to assess the level of psychosocial dysfunctions in
personal, familial, social, vocational, and cognitive areas of each patient.
RESULTS: Qualitative data were analyzed using Chi-square and quantitative data
were analyzed using t-test and correlation as a test of significance.
Statistically significant differences (P < 0.05) were found in all five domains
of DAQ between two groups. Statistically significant difference (P < 0.05) was
found between the two groups with respect to severity of the disability.
CONCLUSION: This study confirms that there are definite and substantial
psychosocial dysfunctions in personal, familial, social, vocational, and
cognitive spheres with the advancement of the duration of illness in chronic
schizophrenic patients.
PMID- 28515554
TI - Personality Profile and Short-term Treatment Outcome in Patients with Alcohol
Dependence: A Study from South India.
AB - BACKGROUND: Studying personality profiles allows researchers to generate
important hypotheses in risk factors and correlates of alcohol use/misuse.
Studies examining the association between personality traits and treatment
outcome are limited in India. We studied the correlation between personality and
treatment outcome in patients with alcohol dependence. METHODS: Adult
participants with alcohol dependence were recruited from the inpatient and
outpatient wards of de-addiction unit of a tertiary care facility in India using
a prospective design and followed up after 3 months. Questionnaires administered
were revised NEO personality inventory (NEO-PI-R), alcohol use disorders
identification test, and advanced warning of alcohol relapse (AWARE). RESULTS:
Out of 99 recruited participants (92% males) with mean age of 37 (+/-8.36) years,
82 (82.8%) patients were followed up to 3 months. E4 (activity) facet of the
extraversion domain in the NEO-PI-R significantly correlated with the baseline
drinking scores (r = 0.204, P = 0.042, n = 99) and AWARE scores (r = 0.276, P =
0.043, n = 54). There was a significant negative correlation between the E2
(gregariousness) facet and satisfaction with life scores (r = -0.211, P = 0.036,
n = 99). Age at first drink was significantly lower among relapsers (P = 0.021).
CONCLUSION: Our study suggests that factors related to extraversion,
specifically, high activity might be associated with higher drinking as well as
higher risk of alcohol relapse. Predicting alcohol relapse by studying the
personality traits would help clinicians in improving treatment outcomes.
PMID- 28515556
TI - Subacute Noninfective Inflammatory Encephalopathy: Our Experience and Diagnostic
Problems.
AB - INTRODUCTION: Immune dysregulation associated encephalopathies present with
significant psychiatric manifestations and only a few soft neurological and
general systemic features. They are generally resistant to treatment with
psychiatric medications. Generalized orthostatic myoclonus and faciobrachial
dystonic seizures are mistaken as Creutzfeldt-Jakob disease and subacute
sclerosing panencephalitis. PATIENTS AND METHODS: Forty-two patients seen during
2010-2015 and diagnosed as noninfective encephalopathy were analyzed. Those
patients with infective causes and those who had significant features of systemic
manifestations of vasculitis and other disorders of central nervous system were
excluded from the study. They were investigated with cerebrospinal fluid imaging,
electroencephalogram (EEG), and antibody profile. RESULTS: More than 70% patients
had psychiatric manifestation as presenting features and reported to
psychiatrist. Three patients had paraneoplastic and others N-methyl-D-aspartate,
voltage-gated potassium channel, thyroid peroxidase, antinuclear antibody
related, and few were due to unknown antibody. CONCLUSION: Serious diagnostic
errors are common and early diagnosis is based on high degree suspicion in
patients presenting with new-onset refractory psychosis. Soft neurological
features should be looked for and EEG serves as a very sensitive tool in
establishing organicity.
PMID- 28515555
TI - Quantitative Balance and Gait Measurement in Patients with Frontotemporal
Dementia and Alzheimer Diseases: A Pilot Study.
AB - INTRODUCTION: Alzhiemers disease and Frontotemporal dementia are common
neurodegenerative dementias with a wide prevalence. Falls are a common cause of
morbidity in these patients. Identifying subclinical involvement of these
parameters might serve as a tool in differential analysis of these distinct
parameters involved in these conditions and also help in planning preventive
strategies to prevent falls. PATIENTS AND METHODS: Eight patients in age and
gender matched patients in each group were compared with normal controls.
Standardizes methods of gait and balance aseesment were done in all persons.
RESULTS: Results revealed subclinical involvement of gait and balancesin all
groups specially during divided attention. The parameters were significantly more
affected in patients. Patients with AD and FTD had involement of over all
ambulation index balance more affected in AD patients FTD patients showed step
cycle, stride length abnormalities. DISCUSSION: There is balance and gait
involvement in normal ageing as well as patients with AD and FTD. The pattern of
involvement in AD correlates with WHERE pathway involvement and FTD with frontal
subcortical circuits involvement. CONCLUSION: Identification the differential
patterns of involvement in subclinical stage might help to differentiate normal
ageing and the different types of cortical dementias. This could serve as an
additional biomarker and also assist in initiating appropriate training methods
to prevent future falls.
PMID- 28515557
TI - Dandy-Walker Variant with Schizophrenia: Comorbidity or Cerebellar Cognitive
Affective Syndrome?
AB - Dandy-Walker complex (DWC) is a series of neurodevelopmental anomalies involving
the posterior cranial fossa. The cerebellum has long been considered to be
involved in motor coordination and balance. However, it has now been noted to
play an important role in higher order cognitive, emotional, and behavioral
functions. The concept of cerebellar cognitive affective syndrome, describing a
coherent spectrum of cognitive and behavioral disturbances in adults following
cerebellar damage has long been proposed. There have been reported cases of co
occurring psychiatric symptoms and DWC in literature, but the conclusive evidence
for an association between the same remains lacking. Herein, we report a case of
schizophrenia presenting along with Dandy-Walker Variant.
PMID- 28515558
TI - A Rare Case of Complicated Opioid Withdrawal in Delirium Without Convulsions.
AB - Opioids are one of the commonly abused substances in India. Opioid withdrawal
symptoms classically include severe muscle cramps, bone aches, autonomic
symptoms, anxiety, restlessness, insomnia, and temperature dysregulation.
However, reports of cases with delirium during withdrawal are few. A 25-year-old
male with severe opioid withdrawal symptoms developed delirium. Investigations
were normal. There were no comorbidities, no significant past history and family
history. Patient treated for opioid dependence with tapering doses of lorazepam
and clonidine. He was discharged with naltrexone. Patient lapsed 3 months later
with similar presentation. Complications such as convulsions and delirium are
recognized in alcohol withdrawal. However, these are rare as a feature of opioid
withdrawal. This case illustrates the need for psychiatrists and physicians to be
aware of the possibilities of delirium with opioid withdrawal and monitoring for
the same is important because of its complications.
PMID- 28515559
TI - Arachnoid Cyst and Psychosis: The Troublemaker or Innocent Bystander.
AB - Organic underpinning of a psychotic disturbance is often missed. Arachnoid cysts
are considered a rare neurological tumor, few of which exhibit any
symptomatology. In most cases, they are diagnosed by accident. Literature
regarding the coexistence of arachnoid cysts with psychiatric disorders is
sparse. Here, we present a case who presented with a typical presentation of
psychosis which was not enough for suspecting for an organic etiology.
PMID- 28515560
TI - Pseudocyst Pancreas with Delirium in a Married Alcohol Dependent Male: A Rare
Presentation.
AB - We herein present a patient with a history of heavy alcohol abuse who developed
pseudocyst Pancreas and delirium, who came to our hospital for treatment. The
patient recovered well with treatment.
PMID- 28515561
TI - Efficacy of Myofascial Unwinding and Myofascial Release Technique in a Patient
with Somatic Symptoms - A Case Report.
AB - Depression is an aversion to activity disorder which could lead to somatic
dysfunctions such as insomnia, excessive sleeping, body aches, listlessness, and
irritable bowel syndrome. The World Health Organization has projected the
depression to be the second leading cause of disability worldwide by 2020. The
physical and mental ill effects of somatic depression can be addressed using the
osteopathic manipulative treatment. Therefore, the purpose of the present case
report is to explore the effect of myofascial release (MFR) technique and
myofascial unwinding (MFU) in the somatic depression. We reported a case of a 39
year-old female diagnosed as dysthymia with moderate depression with somatic
symptoms. She was treated with MFR and MFU for 4 weeks. Depression was scored
using Hamilton Depression Rating Scale (HDRS), and quality of life was measured
using the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q
LES-Q-SF). Both were administered preintervention and 6 weeks postintervention.
The application of MFR and MFU resulted in the improved scores on both HDRS and Q
LES-Q-SF. The present case positive results have proven the effectiveness of MFR
and MFU as an important adjunctive treatment strategy.
PMID- 28515562
TI - Leukodystrophy Presenting as Hyperactivity and Bipolarity with Uncommon Adverse
Drug Reaction.
AB - Leukodystrophy is a group of demyelinating neurodegenerative diseases of brain
with varied presentation and multiple etiologies. Prognosis is predominantly
dismal. Misdiagnosis and wrong treatment are common in this group of rare
neurological disorders, especially when it presents with psychiatric symptoms. In
this case, importance of neurological and radiological evaluation and need for
high diagnostic suspicion in treatment-resistant psychiatric disorders is
highlighted.
PMID- 28515563
TI - Secondary Eating Disorder: A Reality? Case Report of Post Brain Injury Sequelae.
AB - Traumatic brain injury (TBI) can lead to changes in eating behavior patterns.
This report describes the case of a patient with alcohol dependence presenting
with behavioral changes and eating disorder following frontal lobe trauma. A 42
year-old male, premorbidly well-adjusted presented with alcohol use in dependent
pattern for years. He sustained a subdural hematoma in the frontal lobe following
a road traffic accident 10 years back. Post-TBI, the patient, started having low
frustration tolerance, aggressive outbursts, disinhibition, difficulty in
persisting with tasks, apathy, amotivation, and craving for food with inability
to control intake on the sight of food. On testing, a deficit in frontal lobe
functions was seen. Magnetic resonance imaging scan showed large areas of gliosis
and encephalomalacia involving both frontal lobes with parenchymal loss. Eating
disorders have been reported after TBI. This case report underscores a major role
of frontal-subcortical circuits in regulation of eating habits.
PMID- 28515565
TI - Cushing's Syndrome and Treatment-Resistant Depression.
PMID- 28515564
TI - Delayed Stevens-Johnson Syndrome Secondary to the Use of Lamotrigine in Bipolar
Mood Disorder.
AB - Lamotrigine is a mood-stabilizing drug used in maintenance treatment of bipolar I
disease. There are adverse effects with lamotrigine such as a headache, blurred
vision, diplopia, somnolence, ataxia, dizziness, rash, Stevens-Johnson syndrome
(SJS), and toxic epidermal necrolysis. SJS is a life-threatening, blistering
mucocutaneous disease. SJS is characterized by the presence of flat, diffuse
erythematous maculopapular rashes with the involvement of <10% of the body
surface area. Standard trigger is drugs including anticonvulsants, antibiotics,
and Mycoplasma pneumoniae infection. We report a case where a patient developed
SJS secondary to delayed-type hypersensitivity reaction after 6 months of the use
of lamotrigine, while his initial response during the first 6 months did not show
any sign of SJS.
PMID- 28515566
TI - Autonomous Sensory Meridian Response: What is It? and Why Should We Care?
PMID- 28515567
TI - Asymmetric, Tender Gynecomastia Induced by Olanzapine in a Young Male.
PMID- 28515568
TI - Gender Differences in Persistent Delusional Disorder.
PMID- 28515569
TI - Salami Slicing of Data Set, Translational Plagiarism, and Self-plagiarism: The
Storyline.
PMID- 28515570
TI - Association between hemodynamic modifications and clinical outcome of
intracranial aneurysms treated using flow diverters.
AB - Treatment of intracranial aneurysms (IAs) has been revolutionized by the advent
of endovascular Flow Diverters (FDs), which disrupt blood flow within the
aneurysm to induce pro-thrombotic conditions, and serves as a scaffold for
endothelial ingrowth and arterial remodeling. Despite good clinical success of
FDs, complications like incomplete occlusion and post-treatment rupture leading
to subarachnoid hemorrhage have been reported. In silico computational fluid
dynamic analysis of the pre- and post-treated geometries of IA patients can shed
light on the contrasting blood hemodynamics associated with different clinical
outcomes. In this study, we analyzed hemodynamic modifications in 15 IA patients
treated using a single FD; 10 IAs were completely occluded (successful) and 5
were partially occluded (unsuccessful) at 12-month follow-up. An in-house virtual
stenting workflow was used to recapitulate the clinical intervention on these
cases, followed by CFD to obtain pre- and post-treatment hemodynamics. Bulk
hemodynamic parameters showed comparable reductions in both groups with average
inflow rate and aneurysmal velocity reduction of 40.3% and 52.4% in successful
cases, and 34.4% and 49.2% in unsuccessful cases. There was a substantial
reduction in localized parameter like vortex coreline length and Energy Loss for
successful cases, 38.2% and 42.9% compared to 10.1% and 10.5% for unsuccessful
cases. This suggest that for successfully treated IAs, the localized complex
blood flow is disrupted more prominently by the FD as compared to unsuccessful
cases. These localized hemodynamic parameters can be potentially used in
prediction of treatment outcome, thus aiding the clinicians in a priori
assessment of different treatment strategies.
PMID- 28515571
TI - Estimating yield gaps at the cropping system level.
AB - Yield gap analyses of individual crops have been used to estimate opportunities
for increasing crop production at local to global scales, thus providing
information crucial to food security. However, increases in crop production can
also be achieved by improving cropping system yield through modification of
spatial and temporal arrangement of individual crops. In this paper we define the
cropping system yield potential as the output from the combination of crops that
gives the highest energy yield per unit of land and time, and the cropping system
yield gap as the difference between actual energy yield of an existing cropping
system and the cropping system yield potential. Then, we provide a framework to
identify alternative cropping systems which can be evaluated against the current
ones. A proof-of-concept is provided with irrigated rice-maize systems at four
locations in Bangladesh that represent a range of climatic conditions in that
country. The proposed framework identified (i) realistic alternative cropping
systems at each location, and (ii) two locations where expected improvements in
crop production from changes in cropping intensity (number of crops per year)
were 43% to 64% higher than from improving the management of individual crops
within the current cropping systems. The proposed framework provides a tool to
help assess food production capacity of new systems (e.g. with increased cropping
intensity) arising from climate change, and assess resource requirements (water
and N) and associated environmental footprint per unit of land and production of
these new systems. By expanding yield gap analysis from individual crops to the
cropping system level and applying it to new systems, this framework could also
be helpful to bridge the gap between yield gap analysis and cropping/farming
system design.
PMID- 28515572
TI - A family of Fe-N-C oxygen reduction electrocatalysts for microbial fuel cell
(MFC) application: Relationships between surface chemistry and performances.
AB - Different iron-based cathode catalysts have been studied for oxygen reduction
reaction (ORR) in neutral media and then applied into microbial fuel cells (MFC).
The catalysts have been synthesized using sacrificial support method (SSM) using
eight different organic precursors named Niclosamide, Ricobendazole, Guanosine,
Succinylsulfathiazole, Sulfacetamide, Quinine, Sulfadiazine and Pyrazinamide.
Linear Sweep Voltammetry (LSV) curves were obtained for the catalysts using a O2
saturated in 0.1 M potassium phosphate buffer and 0.1 M KCl solution and a
Rotating Ring Disk Electrode (RRDE) setup in order to study the ORR
characteristics. Additionally, we analyze the peroxide yield obtained for each
catalyst which helps us determine the reaction kinetics. Those catalysts have
been mixed with activated carbon (AC), carbon black (CB) and PTFE and pressed on
a metallic mesh forming a pellet-like gas diffusion electrode (GDE). Results
showed that Fe-Ricobendazole, Fe-Niclosamide and Fe-Pyrazinamide had the highest
cathode polarization curves and highest power densities output that was above 200
MUWcm-2. Fe-Ricobendazole, Fe-Niclosamide, Fe-Pyrazinamide, Fe-Guanosine Fe
Succinylsulfathiazole and Fe-Sulfacetamide outperformed compared to Pt cathode.
Fe-Sulfadiazene and Fe-Quinine performed better than AC used as control but less
than Pt. Correlation of surface composition with performance showed that power
density achieved is directly related to the total amount of nitrogen, and in
particularly, N coordinated to metal and pyridinic and pyrrolic types while
larger amounts of graphitic nitrogen result in worse performance.
PMID- 28515573
TI - Problematisations of Complexity: On the Notion and Production of Diverse
Complexities in Healthcare Interventions and Evaluations.
AB - Within the literature on the evaluation of health (policy) interventions,
complexity is a much-debated issue. In particular, many claim that so-called
'complex interventions' pose different challenges to evaluation studies than
apparently 'simple interventions' do. Distinct ways of doing evaluation entail
particular ontologies and epistemologies of complexity. They differ in terms of
whether they define complexity as a quantitative trait of interventions, whether
they see evaluation as part of or outside the intervention, and whether
complexity can be regarded as an emergent property of the intervention and its
evaluation. In practice, evaluators and commissioners of large health care
improvement programmes rely on different, sometimes contradictory, repertoires
about what it means to conduct a 'good' evaluation. This is an ongoing matter
negotiated between and among commissioners, researchers, and-sometimes-programme
managers. In particular, notions of evaluability, usefulness and
distance/independence are problematised in different ways and with diverse
consequences, which, in turn, produce other notions and layers of complexity such
as temporal, institutional and affective complexities. When (social science)
researchers claim that one method or another is better able to grasp complexity,
they elide the issue that any methodological choice emphasises some complexities
and lets others fade into the background. Analysing the practicalities and
emotions involved in evaluation studies opens up the notion of complexity to
analytical scrutiny, and suggests a basis for co-theorising between biomedical,
public health and social scientists (including Science and Technology Studies
scholars).
PMID- 28515574
TI - Autistic Heterogeneity: Linking Uncertainties and Indeterminacies.
AB - Autism is a highly uncertain entity and little is said about it with any degree
of certainty. Scientists must, and do, work through these uncertainties in the
course of their work. Scientists explain uncertainty in autism research through
discussion of epistemological uncertainties which suggest that diverse methods
and techniques make results hard to reconcile, ontological uncertainties which
suggest doubt over taxonomic coherence, but also through reference to autism's
indeterminacy which suggests that the condition is inherently heterogeneous.
Indeed, indeterminacy takes two forms-an inter-personal form which suggests that
there are fundamental differences between individuals with autism and an intra
personal form which suggests that no one factor is able to explain all features
of autism within a given individual. What is apparent in the case of autism is
that scientists put uncertainty and indeterminacy into discussion with one
another and, rather than a well-policed epistemic-ontic boundary, there is a
movement between, and an entwinement of, the two. Understanding scientists'
dialogue concerning uncertainty and indeterminacy is of importance for
understanding autism and autistic heterogeneity but also for understanding
uncertainty and 'uncertainty work' within science more generally.
PMID- 28515576
TI - Quality program in radiology: Persue or perish.
PMID- 28515575
TI - Controls of primary production in two phytoplankton blooms in the Antarctic
Circumpolar Current.
AB - The Antarctic Circumpolar Current has a high potential for primary production and
carbon sequestration through the biological pump. In the current study, two large
scale blooms observed in 2012 during a cruise with R.V. Polarstern were
investigated with respect to phytoplankton standing stocks, primary productivity
and nutrient budgets. While net primary productivity was similar in both blooms,
chlorophyll a -specific photosynthesis was more efficient in the bloom closer to
the island of South Georgia (39 degrees W, 50 degrees S) compared to the open
ocean bloom further east (12 degrees W, 51 degrees S). We did not find evidence
for light being the driver of bloom dynamics as chlorophyll standing stocks up to
165 mg m-2 developed despite mixed layers as deep as 90 m. Since the two bloom
regions differ in their distance to shelf areas, potential sources of iron vary.
Nutrient (nitrate, phosphate, silicate) deficits were similar in both areas
despite different bloom ages, but their ratios indicated more pronounced iron
limitation at 12 degrees W compared to 39 degrees W. While primarily the supply
of iron and not the availability of light seemed to control onset and duration of
the blooms, higher grazing pressure could have exerted a stronger control toward
the declining phase of the blooms.
PMID- 28515577
TI - Presidential address.
PMID- 28515578
TI - Imaging in ductal plate malformations.
AB - Ductal plate malformations are a heterogenous group of congenital fibrocystic
liver diseases resulting from insult to the ductal plate at various stages of
embryogenesis. As a result various biliary malformations, cysts, hamartomas and
congenital hepatic fibrosis may be seen. We present a radiological pictorial of
ductal plate malformations, accurate diagnosis of which is important for clinical
management.
PMID- 28515579
TI - Multimodality imaging of adult gastric emergencies: A pictorial review.
AB - Acute gastric emergencies require urgent surgical or nonsurgical intervention
because they are associated with high morbidity and mortality. Imaging plays an
important role in diagnosis since the clinical symptoms are often nonspecific and
radiologist may be the first one to suggest a diagnosis as the imaging findings
are often characteristic. The purpose of this article is to provide a
comprehensive review of multimodality imaging (plain radiograph, fluoroscopy, and
computed tomography) of various life threatening gastric emergencies.
PMID- 28515580
TI - Infectious pneumonia in the immunocompetent host: What the radiologist should
know.
AB - Lung infections are an important cause of morbidity and mortality, particularly
because of the rising antimicrobial resistance. According to the clinical
setting, they can be categorized as community-acquired pneumonia and hospital
acquired pneumonia. Radiological patterns of lung infections are lobar
consolidation, bronchopneumonia, interstitial pattern, and nodular pattern. In
addition, typical imaging features of several infections serve as "red flag
signs" in reaching a diagnosis or altering the management. It would be prudent
for the radiologist to be well informed regarding these aspects of lung
infections to be able to make a valuable contribution to the management.
PMID- 28515581
TI - Castleman's disease: A rare indication for endovascular therapy for hemoptysis.
AB - Castleman's disease (CD) is a rare lympho-proliferative disorder due to faulty
immune regulation resulting in proliferation of lymphatic tissue. The vascular
supply to these lesions have been reported to arise from the bronchial, internal
mammary and the intercostal arteries. We report a case of hemoptysis secondary to
intrathoracic CD with vascular supply arising from the left inferior phrenic
artery which was successfully embolised with polyvinyl alcohol (PVA) particles.
PMID- 28515582
TI - Evaluation of MR perfusion abnormalities in organophosphorus poisoning and its
correlation with SPECT.
AB - AIM: Acute organophosphate (OP) pesticide poisoning causes substantial morbidity
and mortality worldwide. Many imaging modalities, such as computerized tomography
(CT), magnetic resonance imaging (MRI), and single photon emission computed
tomography (SPECT) of the brain, have been used for quantitative assessment of
the acute brain insult caused by acute OP poisoning. Perfusion defects on SPECT
in acutely poisoned patients with OPs have been described, however, MR perfusion
abnormalities have not been described in the literature. MR perfusion Imaging has
the advantage of having higher spatial resolution, no radiation, and better
availability. MATERIALS AND METHODS: In this prospective study, 20 patients who
ingested OP compounds were included. All the patients underwent brain SPECT on a
dual head SPECT gamma camera and MRI brain on a 1.5T MR system. Neurocognitive
tests were performed for all patients. RESULTS: SPECT showed perfusion defects in
7 patients and total number of perfusion defects were 29. On MR perfusion, based
on the cut-off values of normalized cerebral blood volume (nCBV) ratios and
normalized cerebral blood flow (nCBF) ratios, the total number of patients
showing perfusion defects were 6 and 8; and the total number of perfusion defects
were 29 and 45, respectively. There was significant difference of the nCBV ratios
and nCBF ratios between the control group (n = 20) and positive patients group (n
= 6 and n = 8, respectively) (P > 0.05). All the defects seen on SPECT were well
appreciated on nCBF maps (MRI perfusion) suggestive of 100% correlation.
CONCLUSION: MR perfusion imaging can be used as an effective modality for
evaluation in acute OP poisoning.
PMID- 28515583
TI - Cavernous sinus melanoma: A rare tumor.
AB - Primay melanoma of the cavernous sinus is very rare with only few cases reported
in the literature. We present the cross-sectional imaging findings of this rare
tumor. The differential diagnosis for cavernous sinus mass lesion is wide as it
contains vital neurovascular structures that may be affected by vascular,
neoplastic, infective, and infiltrative lesions arising in the cavernous sinus
proper or via extension from adjacent intra and/or extracranial regions.
Radiologic imaging can narrow the differential diagnosis, however, imaging cannot
definitely reach single diagnosis if they present in atypical form with hemorrage
and cystic degeneration. This case report illustrates that primary cavernous
sinus melanoma may present as a atypical tumor with diagnostic dilemma.
PMID- 28515584
TI - Frontal sinus osteoma with pneumocephalus: A rare cause of progressive
hemiparesis.
AB - Osteomas of paranasal sinuses are common benign tumors and are diagnosed
incidentally. However, osteomas complicated by pneumocephalus with air fluid
level presenting with progressive hemiparesis is rare. Here, we present a case
report of a 22-year-old male who presented with left-sided progressive
hemiparesis with history of generalized headache since 2 years.
PMID- 28515585
TI - Calcification of the submandibular gland in a patient with chickenpox.
AB - The pneumonia virus of chickenpox is now known to cause scattered calcified foci
in the lungs, however to our knowledge, recent literature has not discussed
calcification in the salivary glands. A 15-year-old boy consulted the department
of radiology because of a swelling on the right side of the submandibular area.
Radiological assessment included an ultrasonography and computerized tomography
scan of the neck area, which demonstrated intraparenchymal amorph calcification,
with approximately 13 mm diameter in the right submandibular gland. General
condition and oral intake was good without distress in the patient, and hence he
was discharged on the seventh day of follow-up treatment.
PMID- 28515586
TI - Utility of supplemental screening with breast ultrasound in asymptomatic women
with dense breast tissue who are not at high risk for breast cancer.
AB - OBJECTIVE: To assess the results of an initial round of supplemental screening
with hand-held bilateral breast ultrasound following a negative screening
mammogram in asymptomatic women with dense breast tissue who are not at high risk
for breast cancer. MATERIALS AND METHODS: A retrospective, Health Insurance
Portability and Accountability Act compliant, Institutional Research Board
approved study was performed at a single academic tertiary breast center.
Informed consent was waived. A systematic review of the breast imaging center
database was conducted to identify and retrieve data for all asymptomatic women,
who were found to have heterogeneously dense or extremely dense breast tissue on
screening bilateral mammograms performed from July 1, 2010 through June 30, 2012
and who received a mammographic final assessment American College of Radiology's
(ACR) Breast Imaging Reporting and Data System (BI-RADS) category 1 or BI-RADS
category 2. Hand-held screening ultrasound was performed initially by a
technologist followed by a radiologist. Chi-square and t-test were used and
statistical significance was considered at P < 0.05. RESULTS: A total of 1210
women were identified. Of these, 394 underwent the offered supplemental screening
ultrasound. BI-RADS category 1 or 2 was assigned to 323 women (81.9%). BI-RADS
category 3 was assigned to 50 women (12.9%). A total of 26 biopsies/aspirations
were recommended and performed in 26 women (6.6%). The most common finding for
which biopsy was recommended was a solid mass (88.5%) with an average size of 0.9
cm (0.5-1.7 cm). Most frequent pathology result was fibroadenoma (60.8%). No
carcinoma was found. CONCLUSION: Our data support the reported occurrence of a
relatively high number of false positives at supplemental screening with breast
ultrasound following a negative screening mammogram in asymptomatic women with
dense breast tissue, who are not at a high risk of developing breast cancer, and
suggests that caution is necessary in establishing wide implementation of this
type of supplemental screening for all women with dense breast tissue without
considering other risk factors for breast cancer.
PMID- 28515587
TI - Fetal intra abdominal umbilical vein varix: Case series and review of literature.
AB - Fetal intraabdominal umbilical vein varix (FIUV) is focal dilatation of the
intrabdominalumbilical vein of thefetus. It appears as a round or fusiform cystic
structure in thefetal abdomen, which shows continuity with the umbilical vein
ongrayscale andcolor Dopplerimaging. The diagnostic criteria include the FIUV
varix diameter at least 50% wider than the diameter of the intrahepatic umbilical
veinand an intraabdominal umbilical vein diameter exceeding 9 mm orgreater than
twostandard deviations above the mean for gestational age. We report three cases,
two cases with isolated FIUV and favorable outcome and the third case with FIUV
and atrioventricular septal defect, where trisomy 21 (Down syndrome) was
diagnosed.
PMID- 28515588
TI - Placental mesenchymal dysplasia: What every radiologist needs to know.
AB - Placental mesenchymal dysplasia (PMD) is an uncommon vascular anomaly of the
placenta characterized by placentomegaly with multicystic placental lesion on
ultrasonography and mesenchymal stem villous hyperplasia on histopathology.
Placental mesenchymal dysplasia should be considered in the differential
diagnosis of cases of multicystic placental lesion such as molar pregnancy,
chorioangioma, subchorionic hematoma, and spontaneous abortion with hydropic
placental changes. However, lack of high-velocity signals inside the lesion and a
normal karyotype favor a diagnosis of PMD. PMD must be differentiated from
gestational trophoblastic disease because management and outcomes differ. We
report the case of an 18-year-old female at 15 weeks of gestation with
sonographic findings suggestive of placental mesenchymal dysplasia. The diagnosis
was confirmed on histopathology.
PMID- 28515589
TI - Spectrum of pulmonary valve morphology and its relationship to pulmonary trunk in
tetralogy of Fallot.
AB - BACKGROUND: Tetralogy of Fallot (TOF) is a complex congenital heart disease with
anatomic variations. Although the pulmonary valve in TOF is abnormal, it has not
been studied well, especially on newer imaging modalities such as multidetector
computed tomography (CT), which gives excellent anatomic detail. AIMS: The aim of
this study was to assess the morphology of pulmonary valve in TOF on CT and
evaluate its association with the degree of hypoplasia of infundibulum and
pulmonary trunk. MATERIALS AND METHODS: The cardiac CT scans of 30 patients with
TOF were reviewed to evaluate the morphology of the pulmonary valve,
infundibulum, and pulmonary arteries. Fisher's exact test was performed to
examine the association between pulmonary valve morphology and degree of
hypoplasia of the infundibulum and pulmonary trunk. RESULTS: 16.7% of patients
with TOF had pulmonary atresia. The prevalence of tricuspid, bicuspid, and absent
valves were 10%, 53.3% and 6.7%, respectively. In another 13.3% of patients,
although valve tissue was present, exact morphology could not be determined on
CT. The commissures of 62.5% of the bicuspid valves were at 12 o'clock and 6
o'clock or slightly off the midline. There was statistically significant
association between valve morphology and degree of infundibular hypoplasia (P <
0.001) and calibre of pulmonary trunk (P < 0.001). CONCLUSION: Morphological
abnormality of the pulmonary valve is common in TOF. The most common type of
pulmonary valve in TOF patients is bicuspid valve with commissures at 12 o'clock
and 6 o'clock or slightly off the midline. Fewer cusps of the pulmonary valve are
associated with a more severe degree of pulmonary artery hypoplasia.
PMID- 28515590
TI - Prenatal diagnosis of a rare aortic arch anomaly with left aortic arch and right
ductus arteriosus: Cross ribbon sign.
AB - Here, we report a fetus with a rare aortic arch anomaly with left aortic arch and
right ductus arteriosus, which has not been reported so far. In this condition,
the aorta extends to the left of the trachea as in normal, while the ductus
arteriosus extends to the right of the trachea and joins the descending aorta
posterior to the trachea, with a cross-ribbon sign.
PMID- 28515591
TI - The current status of pediatric radiology in India: A conference-based survey.
AB - INTRODUCTION: Like most other developing countries, India has a large proportion
of children among its population. However, the facilities for adequate treatment
of this large population is inadequate. The development of pediatric radiology as
a subspecialty is still at an infant stage in India. The goal of our study was to
assess the awareness about the current status of pediatric radiology in India.
MATERIALS AND METHODS: A questionnaire was handed over to all attendees of a
pediatric radiology conference to assess their opinion regarding the adequacy of
pediatric training and practice in India. The questionnaire consisted of 10
multiple-choice and two descriptive questions. Descriptive statistical methods
were used for analyzing the results. RESULTS: Eighty-one out of 400 delegates
responded to the questionnaire. Among these 81 respondents, 50 (61.7%) felt that
exposure to pediatric cases during postgraduate course was inadequate. Sixty
three out of 81 (77.7%) respondents thought that specialized training is required
for practicing pediatric radiology, and 79 respondents (97%) felt that the number
of such training programmes should increase. Forty-five out of 81 respondents
(55.5%) were interested in pursuing pediatric radiology as a career. CONCLUSION:
According to the opinion of the respondents of our survey, pediatric radiology
remains an underdeveloped speciality in India. Considering the proportion of the
population in the pediatric age and the poor health indicators in this age group,
elaborate measures, as suggested, need to be implemented to improve pediatric
radiology training and the care of sick children in India.
PMID- 28515592
TI - Inguinoscrotal hernia in infants: Three case reports in ultrasound diagnosis.
AB - An inguinal hernia occurs when an intestinal loop or part of the omentum or
genital organs passes into the scrotal cavity or labia through an incompletely
obliterated processus vaginalis. Inguinal hernias are most common in preterm
neonates, especially at 32-weeks gestation. Content of hernia is mostly bowel and
ovary/testicles. Presence of uterus in herniated sac is rare, and only few cases
are reported in literature. Hernia is more frequently located on the right side
because the right processus vaginalis closes later than the left. Physical
examination is sufficient to enable diagnosis in most cases. Ultrasound
examination is indicated in patients with inconclusive physical findings, in
patients with acute scrotum, and to investigate contralateral involvement in
patients in whom only a unilateral hernia is clinically evident. Routinely, color
or power Doppler imaging is used in inguinal-scrotal hernia to investigate
intestinal and testicular/ovarian perfusion. Urgent surgery is indicated in
patients with an akinetic dilated bowel loop (a sign of strangulation) or
impaired testicular/ovarian perfusion.
PMID- 28515593
TI - Role of penumbra mechanical thrombectomy device in acute dural sinus thrombosis.
AB - BACKGROUND: In dural venous sinus thrombosis (DVST), the mortality ranges 5-30%.
Deep venous system involvement and septic dural sinus thrombosis have a higher
mortality rate. In acute occlusion, collateral flow may not be established, which
may result in significant edema and mass effect. Endovascular interventions may
be considered as a treatment option in appropriate high-risk patients with DVST.
MATERIALS AND METHODS: Eight patients with magnetic resonance imaging (MRI)
confirmed dural sinus thrombosis, who did not respond to the conventional
standard medical treatment, were subsequently treated with mechanical
thrombectomy using the Penumbra System(r). In all cases, medical treatment
including anticoagulants were continued following the procedure for a minimum
period of 1 year. RESULTS: Recanalization of the dural sinus thrombosis was
achieved in all 8 cases. There were no immediate or late endovascular-related
complications. One death occurred due to an unrelated medical event. At 6 months,
there was notable improvement in the modified Rankin Score (mRS), with 5/8 (62%)
patients achieving mRS of 2 or less. The follow-up ranged between 3 months and 26
months (mean: 14.5 months), and there were no new neurological events during the
follow-up period. CONCLUSION: Cerebral venous sinus thrombosis is a rare but life
threatening condition that demands timely diagnosis and therapy. In cases of
rapidly declining neurological status despite standard therapy with systemic
anticoagulation and anti-edema measures, mechanical thrombectomy could be a
lifesaving and effective option. In this study, good outcomes were observed in
the majority of patients at long-term follow up.
PMID- 28515594
TI - Radiofrequency ablation of osteoid osteoma in common and technically challenging
locations in pediatric population.
AB - CONTEXT: Percutaneous radiofrequency ablation (RFA) of osteoid osteoma has a high
technical and clinical success rate. However, there is limited data on its use in
the pediatric population, especially in technically challenging locations.
OBJECTIVE: To assess the safety and efficacy of computed tomography (CT)-guided
percutaneous RFA of osteoid osteoma in pediatric population. PATIENTS AND
METHODS: From June 2009 to May 2014, 30 patients with osteoid osteoma were
treated with CT-guided RFA in common (25 cases) and technically challenging (five
cases: four near articular surface and one in sacrum) locations. Therapy was
performed under general anesthesia with a three-array expandable RF probe for 6
min at 90 degrees C and power of 60-100 W. The patients were discharged next day
under instruction. The treatment success was evaluated in terms of pain relief
before and after (1 day, 1 month, and 6 months) treatment. RESULTS: Technical
success was achieved in all patients (100%). Primary clinical success was 96.66%
(29 of total 30 patients), despite the pediatric population and atypical
location. One patient had persistent pain after 1 month and was treated
successfully with a second procedure (secondary success rate was 100%). One
patient had immediate complication of weakness of right hand and fingers
extension. No delayed complications were observed. CONCLUSIONS: CT-guided RFA is
relatively safe and highly effective for treatment of osteoid osteoma in
pediatric population, even in technically difficult locations.
PMID- 28515595
TI - Percutaneous transhepatic techniques for management of biliary anastomotic
strictures in living donor liver transplant recipients.
AB - AIM: To retrospectively analyze the percutaneous transhepatic techniques and
their outcome in the management of biliary strictures in living donor liver
transplant (LDLT) recipients. MATERIALS AND METHODS: We retrieved the hospital
records of 400 LDLT recipients between 2007 and 2015 and identified 45 patients
with biliary strictures. Among them, 17 patients (37.8%) (Male: female = 13:4;
mean age, 36.1 +/- 17.5 years) treated by various percutaneous transhepatic
biliary techniques alone or in combination with endoscopic retrograde
cholangiopancreatography (ERCP) were included in the study. The technical and
clinical success of the percutaneous management was analyzed. RESULTS:
Anastomotic strictures associated with leak were found in 12/17 patients (70.6%).
Ten out of 12 (83.3%) patients associated with leak had more than one duct-duct
anastomoses (range, 2-3). The average duration of onset of stricture in patients
with biliary leak was 3.97 +/- 2.68 months and in patients with only strictures
it was 14.03 +/- 13.9 months. In 6 patients, endoscopic-guided plastic stents
were placed using rendezvous technique, plastic stent was placed from a
percutaneous approach in 1 patient, metallic stents were used in 2 patients,
cholangioplasty was performed in 1 patient, N-butyl- 2-cyanoacrylate embolization
was done in 1 child with biliary-pleural fistula, internal-external drain was
placed in 1 patient, and only external drain was placed in 5 patients. Technical
success was achieved in 12/17 (70.6%) and clinical success was achieved in 13/17
(76.5%) of the patients. Posttreatment mean time of follow-up was 19.4 +/- 13.7
months. Five patients (29.4%) died (two acute rejections, one metabolic acidosis,
and two sepsis). CONCLUSIONS: Percutaneous biliary techniques are effective
treatment options with good outcome in LDLT patients with biliary complications.
PMID- 28515596
TI - Balloon occluded retrograde transvenous obliteration for bleeding gastric
varices: Eyes see what the mind knows.
AB - Approximately one in six patients with portal hypertension who develop varices at
sites of portosystemic venous collaterals has gastric varices due to hepatofugal
flow into the gastric veins. Bleeding from gastric varices, though less common,
has a higher mortality and morbidity compared to bleeding esophageal varices,
which are easier to manage endoscopically. The efferent channel for gastric
varices is mostly the gastrorenal shunt (GRS) which opens into the left renal
vein. Balloon-occluded transvenous obliteration (BRTO) involves accessing the GRS
with an aim to temporarily occlude its outflow using a balloon catheter and at
the same time injecting sclerosant mixture within the varix so as to cause its
thrombosis and thereby obliteration. BRTO is one of the mainstays of minimally
invasive treatment for bleeding gastric varices. In the minority of cases where
the GRS is absent, conventional BRTO is technically not possible. However,
accessing the small alternate shunt from the inferior phrenic vein may be
possible if one is aware of its existence.
PMID- 28515598
TI - Gorham's syndrome vs generalized lymphagiomatosis: A close call.
PMID- 28515597
TI - Tibial periosteal ganglion cyst: The ganglion in disguise.
AB - Soft tissue ganglions are commonly encountered cystic lesions around the wrist
presumed to arise from myxomatous degeneration of periarticular connective
tissue. Lesions with similar pathology in subchondral location close to joints,
and often simulating a geode, is the less common entity called intraosseous
ganglion. Rarer still is a lesion produced by mucoid degeneration and cyst
formation of the periostium of long bones, rightly called the periosteal
ganglion. They are mostly found in the lower extremities at the region of pes
anserinus, typically limited to the periosteum and outer cortex without any
intramedullary component. We report the case of a 62 year-old male who presented
with a tender swelling on the mid shaft of the left tibia, which radiologically
suggested a juxtacortical lesion extending to the soft tissue or a soft tissue
neoplasm eroding the bony cortex of tibia. It was later diagnosed definitively as
a periosteal ganglion in an atypical location, on further radiologic work-up and
histopathological correlation.
PMID- 28515599
TI - Author's reply.
PMID- 28515600
TI - A novel presentation of tubular adenoma of the breast as an intraductal mass:
Diagnostic considerations and pathologic correlation.
PMID- 28515601
TI - Quality Indicators Compliance Survey in Indian Intensive Care Units.
AB - CONTEXT: The quality of health care and outcomes of Intensive Care Unit (ICU)
have been a major subject of discussion in the past decade. Quality indicators in
ICUs maintain an order of uniformity and standard care of delivery across ICUs.
AIMS: In this study, we tried to analyze the percentage compliance of quality
indicators in ICU across our country. METHODS: Four hundred complete
questionnaire forms were collected in two stages by means of conducting a survey
and through email responses to the survey questionnaire. Data were tabulated and
evaluated in percentage responses. RESULTS: Monitoring of infection control
measures such as hand hygiene (77%), monitoring of ICU-acquired infections
(>75%), and quality and policy measures (>70%) were promising. Improvements are
required in following end-of-life pathways (52%) and staffing patterns in ICU.
ICU discharge timings (41%), standardized mortality ratio monitoring (39%), and
multidisciplinary rounds (58%) in ICUs are few areas we need to develop further.
CONCLUSION: The future of critical care looks promising with growing number of
trained intensivists and hospitals functioning with an average ICU bed strength
of 30-40. Such surveys need to be performed regularly to improve the patient care
and safety across ICUs.
PMID- 28515602
TI - Respiratory Multiplex Polymerase Chain Reaction: An Important Diagnostic Tool in
Immunocompromised Patients.
AB - BACKGROUND: Viruses and atypical pathogens can cause significant respiratory
illness in immunocompromised patients. Multiplex polymerase chain reaction (MPCR)
has improved the diagnostic yield of pathogens, and it is easier to identify the
co-infections also. The present study was done to evaluate the performance of
MPCR on bronchoalveolar lavage (BAL) samples in immunocompromised patients.
METHODS: Atotal of 177 BAL specimens collected over a 19 months period from
immunocompromised patients with respiratory illness were analyzed with the MPCR
and aerobic culture. Patients were divided into four according to the pathogens.
Category V (only viral), Category NV (nonviral, i.e., bacteria and atypical),
Category M (mixed, i.e., both viral and nonviral pathogen), and Category UK
(unknown etiology). RESULTS: MPCR identified the causative pathogen in 59.3% of
patients while culture could identify only in 37.8% of patients. Most frequent
etiological agent was Klebsiella pneumoniae (32%), followed by cytomegalovirus
(21%), and Pneumocystis jirovecii (10%). Numbers of patients in each category
were Category V (9.6%), Category NV (43.5%), Category M (19.8%), and Category UK
(27.1%). Mortality was significantly higher in patients of Category M having
mixed infections. CONCLUSION: MPCR is highly sensitive and rapid tool which can
be considered in the routine diagnostic algorithm of respiratory illness in
immunocompromised patients.
PMID- 28515604
TI - Development and Psychometric Evaluation of the Pre-hospital Medical Emergencies
Early Warning Scale.
AB - INTRODUCTION: The number of requests for emergency medical services (EMSs) has
increased during the past decade. However, most of the transports are not
essential. Therefore, it seems crucial to develop an instrument to help EMS staff
accurately identify patients who need pre-hospital care and transportation. The
aim of this study was to develop and evaluate the psychometric properties of the
Pre-hospital Medical Emergencies Early Warning Scale (Pre-MEWS). MATERIALS AND
METHODS: This mixed-method study was conducted in two phases. In the first phase,
a qualitative content analysis study was conducted to identify the predictors of
medical patients' need for pre-hospital EMS and transportation. In the second
phase, the face and the content validity as well as the internal consistency of
the scale were evaluated. Finally, the items of the scale were scored and scoring
system was presented. RESULTS: The final version of the scale contained 22 items
and its total score ranged from 0 to 54. CONCLUSIONS: Pre-MEWS helps EMS staffs
properly understand medical patients' conditions in pre-hospital environments and
accurately identify their need for EMS and transportation.
PMID- 28515603
TI - Correlation of Serum Vitamin D Level with Mortality in Patients with Sepsis.
AB - BACKGROUND: Sepsis is the leading cause of mortality in the critically ill.
Recently, it has been found in many studies that many trace elements and
nutrients do have an effect on human body and if supplemented can improve the
prognosis in patients with sepsis. AIM AND OBJECTIVES: Primary objective: Whether
low Vitamin D is associated with mortality. Secondary objective: To find out
association of low Vitamin D levels and morbidity in terms of length of hospital
and Intensive Care Unit (ICU) stay. SUBJECTS AND METHODS: Following ethical
approval, consent will be sought from either the patient or assent from a near
relative. Successive patients admitted to the medical emergency and ICU at
tertiary care health center who fulfill the following criteria for sepsis, within
a 24 h time window, were included in the study. RESULTS: Among 88 patients
evaluated in our study 15 patients (18.2%) were found to have adequate Vitamin D
levels and seven patients (8%) were found insufficient and rest 52 patients
(73.9%) were found deficient in Vitamin D. Age of the patients ranged between 18
and 82 years with mean (+/-standard deviation) 45.02 +/- 17.69 years. Mean
Vitamin D level was found significantly higher among patients with positive
outcome than those with unfavorable outcome (expiry) (t = 2.075, P = 0.04). On
comparison of the length of hospital stay (morbidity) with Vitamin D levels, we
found statistically significant inverse relation between Vitamin D levels and
length of hospital stay. CONCLUSION: Vitamin D deficiency leads to increased risk
of mortality in the critically ill along with prolonged hospital stay.
PMID- 28515606
TI - Gender-based Assessment of Survival in Trauma-hemorrhagic Shock: A Retrospective
Analysis of Indian Population.
AB - INTRODUCTION: Trauma-hemorrhagic shock (THS) is a leading cause of death. Female
rats and women experience better outcomes in terms of survival after major trauma
as compared to males. There are limited data in Indian population. Authors
studied the gender-based outcome of patients with Class IV hemorrhagic shock due
to blunt trauma and the distribution of factors among males and females which are
known to affect outcome. MATERIALS AND METHODS: It was a retrospective study with
data of trauma victims between January 2008 and July 2013. Road traffic crash
(RTC), fall, or assault of all ages with Class IV hemorrhagic shock on arrival
was included in the study, and data were collected on demographic, clinical, and
laboratory parameters. Drowning, burns, penetrating injuries, and septic,
neurogenic, and cardiogenic shock were excluded from the study. RESULTS: Seven
hundred and eighty-one patients were analyzed under three groups: (i) overall
group including all patients (n = 781), (ii) male group (n = 609), and (iii)
female group (n = 172). After adjusting all variables, mortality was
significantly lower in females as compared to males following THS (P < 0.05).
Age, blood pressure, pulse, male gender, and fall and RTC as mode of injury (MOI)
were independent predictors of mortality (P < 0.05) in overall group. Among
males, age, pulse, and RTC as a MOI were significant (P < 0.05), while in
females, only systolic blood pressure (SBP) was independent predictor of
mortality. CONCLUSION: Females had better survival as compared to males following
THS. SBP was an independent predictor of mortality in females with THS.
PMID- 28515605
TI - Influence of Admission Source on the Outcome of Patients in an Intensive Care
Unit.
AB - AIM OF THE STUDY: The admission in the Intensive Care Unit (ICU) occurs from
various sources, and the outcome depends on a complex interplay of various
factors. This observational study was undertaken to describe the epidemiology and
compare the differences among patients admitted in a tertiary care ICU directly
from the emergency room, wards, and ICUs of other hospitals. MATERIALS AND
METHODS: A retrospective study was conducted on 153 consecutive patients admitted
from various sources in a tertiary care ICU between July 2014 and December 2015.
The primary endpoint of the study was the influence of the admission source on
ICU mortality. The secondary endpoints were the comparison of the duration of
mechanical ventilation, length of ICU stay, and the ICU complication rates
between the groups. RESULTS: Out of the 153 patients enrolled, the mortality of
patients admitted from the ICUs of other hospital were significantly higher than
the patients admitted directly from the emergency room or wards/operating rooms
(60.5% vs. 48.2% vs. 31.9%; P = 0.02). The incidence of ventilator-associated
lung injury was lower in the patients admitted directly from the emergency room
(23.4% vs. 50% vs. 50%; P = 0.03). Multivariate logistic regression analysis
revealed higher age, increased disease severity, longer duration of mechanical
ventilation, and longer ICU stay as independent predictors of mortality in the
patients shifted from the ICUs of other hospitals. CONCLUSION: The study
demonstrated a higher risk of ICU mortality among patients shifted from the ICUs
of other hospitals and identified the independent predictors of mortality.
PMID- 28515607
TI - Abrus precatorius Poisoning: A Retrospective Study of 112 Patients.
AB - Abrus precatorius is a rare but important cause of plant poisoning, especially in
tropical countries like India. Most of the published literature on Abrus is
limited a few case reports. Hence, we did a retrospective study the clinical
features and outcome of Abrus poisoning. Case records of patients admitted to
medicine wards during 7 years were included in the study. A total of 112 patients
were studied. The majority were females (78%), and most of the patients were
between 13 and 30 years (81%). Diarrhea was the most common symptom (66%), and
blood in stools was present in (33%). Six patients had died with a mortality rate
of (5.35%).
PMID- 28515608
TI - Thrombotic Thrombocytopenic Purpura in a Case of Dengue Fever: A Rare
Presentation.
AB - Here, we present an unusual occurrence of thrombotic thrombocytopenic purpura
(TTP) in a case of dengue fever. Both the conditions are fatal and can result in
significant mortality and morbidity if left untreated. In this case, as soon as,
we diagnosed the patient as having TTP, we treated her with plasma exchange
therapy, steroids, and monoclonal antibodies such as rituximab. The patient
responded very well to the treatment and completely recovered from neurological
symptoms and laboratory parameters also normalized. Hence, timely diagnosis and
starting appropriate treatment immediately are key factors for successful
outcome.
PMID- 28515609
TI - Not all febrile critical illness with rash is infective: Drug reaction may be a
mimic.
AB - We report a case of ciprofloxacin-related drug rash with eosinophilia and
systemic symptoms (DRESS) which was initially diagnosed and managed on the line
of tropical fever. Later, a diagnosis of definite case of DRESS was made
according to the RegiSCAR scoring system and the patient was managed with the
removal of ciprofloxacin along with steroids. DRESS is a great masquerader. The
diagnosis should be highly suspected in the presence of fever, skin rash, liver
involvement, and hypereosinophilia.
PMID- 28515610
TI - Hyperemia Causing Delayed Recovery in Traumatic Brain Injury.
AB - Subarachnoid hemorrhage is a common manifestation of traumatic brain injury. A
clinical deterioration in Glasgow Coma Scale score without an accompanying
radiological worsening is suggestive of vasospasm. However, hyperemia could be
another possibility which can easily be considered with corroborating
transcranial Doppler (TCD) features. This case report reiterates the value of TCD
in such instances.
PMID- 28515611
TI - Malposition of the Central Venous Catheter: A Diagnostic Dilemma.
AB - A 50-year-old male was admitted to Intensive Care Unit with head and chest injury
needed multiple central venous catheter (CVC) for the long-term intravenous
access. Right internal jugular vein was cannulated uneventfully, and the tip of
CVC was confirmed in the chest radiograph along the right border of the
mediastinum. After few days, left subclavian vein was cannulated and the
procedure was uneventful. However, the postprocedure Chest X-ray showed the CVC
along the left border of mediastinum rather than the right border. Possibility of
CVC in one of the tributaries of left brachiocephalic vein was thought. Due to
uncertainty in position of left CVC, we inserted CVC in right-sided subclavian
vein, which was in normal position along the right border of mediastinum. Left
subclavian CVC was removed. Reviewing the patient's thoracic computed tomography
scan revealed, patient had congenital anomaly and double superior vena cava that
explained the abnormal course of left subclavian CVC along the left border of
mediastinum.
PMID- 28515612
TI - Acute Yellow Phosphorus Poisoning Causing Fulminant Hepatic Failure with
Parenchymal Hemorrhages and Contained Duodenal Perforation.
AB - White phosphorus is well known as a potent hepatotoxin and a severe local and
systemic toxin causing damage to gastrointestinal, hepatic, cardiovascular, and
renal systems. It is used in the manufacture of matches, fireworks, rodenticide,
and fertilizers. Death results due to acute liver failure. Management of yellow
phosphorus (YP) poisoning is supportive with no antidote available. Here, we
present a case of acute YP poisoning in a 25-year-old female presenting with
fulminant hepatic failure and duodenal perforation.
PMID- 28515613
TI - Secondary Sjogren's Syndrome Presenting with Distal Tubular Acidosis and
Quadriparesis.
AB - A 52-year-old female patient was admitted to Intensive Care Unit with complaints
of quadriparesis. Investigations revealed distal renal tubular acidosis (DRTA)
secondary to Sjogren's syndrome with involvement of the parotid and thyroid
glands. Laboratory investigations showed hyperchloremic metabolic acidosis and an
alkaline urine pH with clinical signs of sicca syndrome. Sjogren's syndrome is
associated with DRTA and occurrences of quadriparetic hypokalemia,
nephrolithiasis, and osteomalacia can be prevented with early diagnosis and
lifelong treatment with potassium and alkali replacement.
PMID- 28515614
TI - Symmetrical Peripheral Gangrene in Severe Plasmodium vivax Malaria.
PMID- 28515615
TI - The Tissue Dilator: A Victim or the Aggressor?
PMID- 28515616
TI - Fourier series of sums of products of ordered Bell and poly-Bernoulli functions.
AB - In this paper, we study three types of sums of products of ordered Bell and poly
Bernoulli functions and derive their Fourier series expansion. In addition, we
express those functions in terms of Bernoulli functions.
PMID- 28515617
TI - A modified subgradient extragradient method for solving monotone variational
inequalities.
AB - In the setting of Hilbert space, a modified subgradient extragradient method is
proposed for solving Lipschitz-continuous and monotone variational inequalities
defined on a level set of a convex function. Our iterative process is relaxed and
self-adaptive, that is, in each iteration, calculating two metric projections
onto some half-spaces containing the domain is involved only and the step size
can be selected in some adaptive ways. A weak convergence theorem for our
algorithm is proved. We also prove that our method has [Formula: see text]
convergence rate.
PMID- 28515618
TI - Existence of entire solutions of some non-linear differential-difference
equations.
AB - In this paper, we investigate the admissible entire solutions of finite order of
the differential-difference equations [Formula: see text] and [Formula: see
text], where [Formula: see text], [Formula: see text] are two non-zero
polynomials, [Formula: see text] is a polynomial and [Formula: see text]. In
addition, we investigate the non-existence of entire solutions of finite order of
the differential-difference equation [Formula: see text], where [Formula: see
text], [Formula: see text] are two non-constant polynomials, [Formula: see text],
m, n are positive integers and satisfy [Formula: see text] except for [Formula:
see text], [Formula: see text].
PMID- 28515619
TI - Weighted inequalities for generalized polynomials with doubling weights.
AB - Many weighted polynomial inequalities, such as the Bernstein, Marcinkiewicz,
Schur, Remez, Nikolskii inequalities, with doubling weights were proved by
Mastroianni and Totik for the case [Formula: see text], and by Tamas Erdelyi for
[Formula: see text]. In this paper we extend such polynomial inequalities to
those for generalized trigonometric polynomials. We also prove the large sieve
for generalized trigonometric polynomials with doubling weights.
PMID- 28515620
TI - Stationary acceleration of Frenet curves.
AB - In this paper, the stationary acceleration of the spherical general helix in a 3
dimensional Lie group is studied by using a bi-invariant metric. The relationship
between the Frenet elements of the stationary acceleration curve in 4-dimensional
Euclidean space and the intrinsic Frenet elements of the Lie group is outlined.
As a consequence, the corresponding curvature and torsion of these curves are
computed. In Minkowski space, for the curves on a timelike surface to have a
stationary acceleration, a necessary and sufficient condition is refined.
PMID- 28515621
TI - Inequalities for alpha-fractional differentiable functions.
AB - In this article, we present an identity and several Hermite-Hadamard type
inequalities for conformable fractional integrals. As applications, we establish
some inequalities for certain special means of two positive real numbers and give
the error estimations for the trapezoidal formula.
PMID- 28515622
TI - The influence of genistein on free radicals in normal dermal fibroblasts and
keloid fibroblasts examined by EPR spectroscopy.
AB - Normal and keloid fibroblasts were examined using X-band (9.3 GHz) electron
paramagnetic resonance spectroscopy. The effect of genistein on the concentration
of free radicals in both normal dermal and keloid fibroblasts after ultraviolet
irradiation was investigated. The highest concentration of free radicals was seen
in keloid fibroblasts, with normal fibroblasts containing a lower concentration.
The concentration of free radicals in both normal and keloid fibroblasts was
altered in a concentration-dependent manner by the presence of genistein. The
change in intra-cellular free radical concentration after the ultraviolet
irradiation of both normal and keloid fibroblasts is also discussed. The
antioxidant properties of genistein, using its 1,1-Diphenyl-2-picrylhydrazyl
(DPPH) free radical-scavenging activity as a model, were tested, and the effect
of ultraviolet irradiation on its interaction with free radicals was examined.
The electron paramagnetic resonance spectra of DPPH showed quenching by
genistein. The interaction of genistein with DPPH free radicals in the absence of
ultraviolet irradiation was shown to be slow, but this interaction was much
faster under ultraviolet irradiation. Ultraviolet irradiation enhanced the free
radical-scavenging activity of genistein.
PMID- 28515623
TI - Antibacterial properties of 5-substituted derivatives of rhodanine-3-carboxyalkyl
acids.
AB - A series of rhodanine 3-carboxyalkanoic acid derivatives possessing 4'-(N,N
dialkyl-amino or diphenylamino)-benzylidene moiety as a substituent at the C-5
position were synthesised and their antibacterial activity was screened. All the
rhodanine derivatives showed bacteriostatic or bactericidal activity to the
reference gram-positive bacterial strains, but lack of activity to the reference
Gram-negative bacterial strains and yeast strains was observed.
PMID- 28515624
TI - Closing the gap between plant ecology and Quaternary palaeoecology.
AB - Ecology and Quaternary palaeoecology have largely developed as parallel
disciplines. Although both pursue related questions, information exchange is
often hampered by particularities of the palaeoecological data and a
communicational gap has been perceived between the disciplines. Based on selected
topics and developments mainly in Quaternary palaeoecology, we show that both
disciplines have converged somewhat during recent years, while we still see
untapped potential for closer interactions. Macroecology is probably the
discipline that most easily combines different time-scales and where co
operations between palaeoecologists, geneticists and vegetation modellers have
been inspiring. Quantitative vegetation reconstructions provide robust estimates
of tree composition and land cover at different spatial scales, suitable for
testing hypotheses about long-term vegetation changes or as quantitative
background data in studies on contemporary vegetation patterns. Palaeo-data also
hold yet unexplored potential to study the drivers of long-term diversity and
aspects of functional diversity may facilitate comparisons between continents and
over glacial-interglacial cycles.
PMID- 28515625
TI - Overview of the impact of Typhoid and Paratyphoid fever. Utility of Ty21a vaccine
(Vivotif(r)).
AB - Cases of diarrhoeal disease number from 1.7 to 5 billion per year worldwide. One
of the main causes of diarrhoeal disease is typhoid fever, which is a potentially
life-threatening multi-systemic illness. According to the most recent estimates,
a total of 26.9 million typhoid fever episodes occurred in 2010. The geographical
distribution of the disease differs widely; in developed countries, the incidence
rate per 100,000 per year varies from < 0.1 to 0.3, and the disease mainly
affects people who travel to endemic areas located in low- and middle-income
countries. Low- and middle-income countries are mainly affected owing to the lack
of clean water and proper sanitation. In the fight against this plague,
prevention is fundamental, and vaccination against typhoid is an effective
measure. Vivotif(r) is an oral live attenuated vaccine which contains a mutated
strain of Salmonella (Ty21a) and reproduces the natural infection. The vaccine
was first licensed in Europe in 1983 and in the US in 1989, and over the years it
has proved efficacious and safe. It is indicated for adults and children from 5
years of age upwards. Specifically, in the most developed countries, vaccination
is suggested for highrisk population groups and particularly for international
travellers to destinations where the risk of contracting typhoid fever is high.
It must also be borne in mind that international travel is increasing. Indeed,
international tourist arrivals totalled 1,184 million in 2015 and, on the basis
of current trends, international travel is expected to grow by 3-4% in 2017.
Vivotif(r) appears to be a powerful means of disease prevention, the importance
of which is highlighted by the spread of antibiotic-resistant strains of
Salmonella typhy (S. typhi).
PMID- 28515626
TI - The history of tuberculosis: from the first historical records to the isolation
of Koch's bacillus.
AB - Tuberculosis (TB) is a contagious, infectious disease, due to Mycobacterium
tuberculosis (MT) that has always been a permanent challenge over the course of
human history, because of its severe social implications. It has been
hypothesized that the genus Mycobacterium originated more than 150 million years
ago. In the Middle Ages, scrofula, a disease affecting cervical lymph nodes, was
described as a new clinical form of TB. The illness was known in England and
France as "king's evil", and it was widely believed that persons affected could
heal after a royal touch. In 1720, for the first time, the infectious origin of
TB was conjectured by the English physician Benjamin Marten, while the first
successful remedy against TB was the introduction of the sanatorium cure. The
famous scientist Robert Koch was able to isolate the tubercle bacillus and
presented this extraordinary result to the society of Physiology in Berlin on 24
March 1882. In the decades following this discovery, the Pirquet and Mantoux
tuberculin skin tests, Albert Calmette and Camille Guerin BCG vaccine, Selman
Waksman streptomycin and other anti-tuberculous drugs were developed.
PMID- 28515628
TI - Epidemiology of herpes simplex virus type 1 and 2 in Italy: a seroprevalence
study from 2000 to 2014.
AB - Herpes simplex viruses (HSV) are among the most widespread causative agents of
human viral infections. HSV-2 is one of the commonest causes of genital disease,
while HSV-1 is associated primarily with orolabial ulceration; however, recent
changes in HSV epidemiology showed an increase in genital and neonatal herpes
particularly caused by HSV-1. The main purpose of this study was to assess the
seroprevalence of HSV-1 and HSV-2 in a random population in Siena (central Italy)
in 2000, 2005 and 2013-2014 and in Bari (southern Italy) in 2005. Moreover, a
preliminary study was conducted to investigate the spread of HSV infection in a
population of pregnant women and infants in Bari in 2003, 2004 and 2005. Human
serum samples were tested for the presence of specific anti-HSV-1 and anti-HSV-2
IgG antibodies using a commercially available ELISA test. For the primary
purpose, seroprevalence rates observed in Siena were compared over the years
sampled and with the seroprevalence rate found in Bari. Results of seroprevalence
in Siena show a decreased trend for both viruses, especially in adolescents and
young adults; moreover, HSV-2 seroprevalence rates found in the two cities
suggest geographical differences. For the secondary purpose, prevalence rates
among pregnant women were compared with the seroprevalence found in women of the
general population. No significant difference in prevalence rates were found
among pregnant women, while results indicate both viruses are a source of
infection in infants.
PMID- 28515629
TI - Microbial competition in environmental nosocomial reservoirs and diffusion
capacity of OXA48-Klebsiella pneumoniae: potential impact on patients and
possible control methods.
AB - BACKGROUND: We have found clusters of Klebsiella pneumoniae with OXA48
carbepenemase cases in some hospital rooms, and decided to investigate whether
bathroom siphons could be a reservoir for OXA48 bacteria, as occurs with K.
oxytoca with other types of carbepenemases. METHODS: We evaluated the microbial
competition between strains with OXA48 and VIM carbepenemases, in diluted
nutrient-broth, on a slime germ-carrier. We compared the number of colonies at 5
and 10 days on the contaminated carriers with one or two strains. We evaluated
the dissemination of K. pneumoniae with carbepenemase OXA48 or VIM from thumbs
and index fingers of volunteers, to standard surfaces (20 glass germ-carrier by
each volunteer). After, we counted the number of microorganisms on each carrier.
Microbiological weekly studies of faecal microbiota of all patients were obtained
in Traumatology and Oncology. Moreover, we studied samples of the sink in their
rooms. PCR and MLST sequence-type was determined in all K. pneumoniae diagnosed
from patients and sinks. RESULTS: A large possibility of diffusion from
contaminated hands, which continue to transmit high numbers of microorganisms
after more than 10 successive surface contacts, was highlighted; OXA bacteria
were more persistent than VIM bacteria. Microbial competition studies showed that
VIM bacteria are inhibited by OXA ones. These observations can explain the
concentration of cases of K. pneumoniae OXA48 in some rooms in Traumatology and
Oncology, producing a significant OR between rooms with OXA48-bacteria
contaminated siphons and other rooms (3.1 and 3.3 respectively). Risk was lowered
after changing or disinfecting (heat plus chlorinated disinfectant) the
contaminated siphons. Siphon colonization by VIM bacteria was not related with
human infections by similar microorganisms. CONCLUSIONS: Bathroom siphons can be
a reservoir for K. pneumoniae OXA48 and lead to outbreaks. Outbreaks can be
controlled by replacement or heat plus chemical treatment of the sink-siphons.
PMID- 28515627
TI - Frequently asked questions on seven rare adverse events following immunization.
AB - Routine mass immunization programs have contributed greatly to the control of
infectious diseases and to the improvement of the health of populations. Over the
last decades, the rise of antivaccination movements has threatened the advances
made in this field to the point that vaccination coverage rates have decreased
and outbreaks of vaccine-preventable diseases have resurfaced. One of the
critical points of the immunization debate revolves around the level of risk
attributable to vaccination, namely the possibility of experiencing serious and
possibly irreversible adverse events. Unfortunately, the knowledge about adverse
events, especially rare ones, is usually incomplete at best and the attribution
of a causal relationship with vaccinations is subject to significant
uncertainties. The aim of this paper is to provide a narrative review of seven
rare or very rare adverse events: hypotonic hyporesponsive episode, multiple
sclerosis, apnea in preterm newborns, Guillain-Barre syndrome, vasculitides,
arthritis/ arthralgia, immune thrombocytopenic purpura. We have selected these
adverse events based on our experience of questions asked by health care workers
involved in vaccination services. Information on the chosen adverse events was
retrieved from Medline using appropriate search terms. The review is in the form
of questions and answers for each adverse event, with a view to providing useful
and actionable concepts while not ignoring the uncertainties that remain. We also
highlight in the conclusion possible future improvements to adverse event
detection and assessment that could help identify individuals at higher risk
against the probable future backdrop of ever-greater abandonment of compulsory
vaccination policies.
PMID- 28515630
TI - An exception to the rule "no association between antibiotic resistance and
decreased disinfectant microbicidal efficacy": Orthophthalaldehyde (OPA) and
Pseudomonas aeruginosa isolated from ICU and paraplegic patients.
AB - BACKGROUND: Antibiotic resistance and decreased susceptibility to disinfectants
are not usually associated in microorganisms, but we have found an exception to
this rule: P. aeruginosa versus orthophthalaldehyde (OPA). METHODS: Bactericidal
effect of OPA was measured at 10 minutes on endodoncy files contaminated with an
ATCC strain (control) or 206 strains of P. aeruginosa recently isolated from 206
ICU and paraplegic patients in a tertiary university hospital, in two consecutive
years. RESULTS: Differences in bactericidal effect of OPA were found between the
strains isolated each year (decreased susceptibility in the first period), but in
both years the statistical differences (p < 0.05) were maintained according to
whether the strains were "susceptible" to antibiotics, "resistant" (to one family
of antibiotics) or "multi-resistant" (resistant to more than one family of
antibiotics), exhibiting a reduction in their OPA susceptibility in parallel to
an increase of their antibiotic resistance. In contrast, there were no
differences depending on the type of sample (sputum, urine, faeces, pharynx) or
of patient (paraplegic or ICU: adult, newborn, burn). Finally we selected 15
strains with an OPA effect below 3.5 log10 at 10 minutes and repeated the study
with an OPA exposure of 15 minutes. In these conditions OPA showed a total
bactericidal effect on these P. aeruginosa strains. CONCLUSIONS: There was an
association between antibiotic resistance and decreased OPA susceptibility. This
normally does not require an increase in disinfection time, but, for endoscope
disinfection or instruments from colonized/infected patients with
resistant/multiresistant P. aeruginosa, we consider it better to use 15 min of
OPA. Regular tests (e.g., once every 12 months) with germ-carriers, should be
performed to assess ecological changes in susceptibility to high level
disinfectants and must include not only ATCC strains, but also recently isolated
microorganisms with different antibiotic sensitivities (susceptible, resistant
and multi-resistant).
PMID- 28515631
TI - Water and air ozone treatment as an alternative sanitizing technology.
AB - AIMS: We investigated the effectiveness of ozone (aqueous and gaseous) treatment
as an alternative sanitizing technology to common conventional disinfectants in
reducing the microbial contamination of both water and air. METHODS: Ozone was
added for 20 minutes to a well-defined volume of water and air by the system
named "Ozonomatic(r)". The effectiveness of ozonation was determined by counting
CFU/ m3 or ml of bacteria present in samples of air or water collected before
(T0) and after (T1) the addition of ozone and comparing the microbial load of
different bacteria present in ozonized and nonozonized samples. RESULTS: When the
ozonisation equipment was located at 30 cm from the surface of the water in the
bath tub in which the bacteria investigated were inoculated, the treatment was
able to reduce the total microbial load present in the aerosol by 70.4% at a
temperature of 36 degrees C for 48 hours. Conversely, at 22 degrees C for 5 days,
only a modest decrease (9.1%) was observed. Escherichia coli and Pseudomonas
aeruginosa were completely eliminated. A 93.9% reduction was observed for
Staphylococcus aureus, followed by Streptococcus faecalis (25.9%). The addition
of ozone to water was able to almost eliminate Staphylococcus aureus (98.9%
reduction) and also to exert a strong impact on Legionella pneumophila (87.5%
reduction). Streptococcus faecalis and Pseudomonas aeruginosa showed a decrease
of 64.2% and 57.4%, respectively. Conversely, only a 26.4% reduction was observed
for the bacterium Escherichia coli. This study showed that the addition of ozone
in the air exerted a modest reduction on microbial load at 36 degrees C, whereas
no effect was observed at 22 degrees C. CONCLUSIONS: Aqueous and gaseous ozone
treatments were effective against microbial contaminants, reducing the CFU of the
microorganisms studied. These results confirm the efficacy of the ozone
disinfection treatment of both water and air; particularly, it constitutes an
extremely promising alternative, allowing the possibility to reuse contaminated
water.
PMID- 28515632
TI - Effectiveness of hand hygiene education among a random sample of women from the
community.
AB - OBJECTIVE: The effectiveness of hand hygiene education was investigated by
studying the hand hygiene awareness and bacterial hand contamination among a
random sample of 170 women in the community. METHODS: Questionnaire was used to
assess the hand hygiene awareness score, followed by swabbing of the dominant
hand. Bacterial identification was done by conventional biochemical tests.
RESULTS: Better hand hygiene awareness score was significantly associated with
age, scarce bacterial growth and absence of potential pathogen (p < 0.05). Out of
the 170 hand samples, bacterial growth was noted in 155 (91.2%), which included
91 (53.5%) heavy growth, 53 (31.2%) moderate growth and 11 (6.47%) scanty growth.
The presence of enteric bacteria was associated with long nails (49.4% vs 29.2%;
p = 0.007; OR = 2.3; 95% CI: 1.25-4.44) while finger rings were associated with
higher bacterial load (p = 0.003). Coliforms was significantly higher among women
who had a lower hand hygiene awareness score, washed their hands at lower
frequency (59.0% vs 32.8%; p = 0.003; OR = 2.9; 95% CI: 1.41-6.13) and used
common soap as compared to antiseptic soaps (69.7% vs 30.3%, p = 0.000; OR =
4.11; 95% CI: 1.67-10.12). CONCLUSIONS: Level of hand hygiene awareness among the
participants was satisfactory but not the compliance of hand washing practice,
especially among the elders.
PMID- 28515633
TI - Association between type 2 diabetes mellitus and anthropometric measurements - a
case control study in South India.
AB - INTRODUCTION: Obesity is a major risk factor for type 2 diabetes mellitus (T2DM).
Clinical evidence indicates a stronger association of diabetes with central
obesity than general obesity. The present study aimed to compare the association
between type 2 diabetes mellitus and different anthropometric measurements and
evaluate the usefulness of these measurements in clinical practice. METHODS: A
case-control study was done among 102 individuals; of whom 51 cases included
diagnosed T2DM (>= 20 years age) patients attending the Medicine out-patient
consultation of a tertiary care hospital and 51 controls who were screen negative
for T2DM and recruited from the local community. Various anthropometric
measurements were used according to standard World Health Organization (WHO)
protocols. Data was entered and analyzed using Statistical Package for Social
Sciences (SPSS) version 15. RESULTS: The proportion of cases with Body Mass Index
(BMI) >= 25 kg/m2 was 55% as compared to 22% of controls and this association was
statistically significant (p < 0.05). The proportion of cases with high waist
circumference cut-offs (WC) was 74.5% as compared to 45.1% healthy individuals
and this association was also statistically significant (p < 0.05, OR = 3.56). A
Receiver Operating Characteristic (ROC) curve for both gender revealed highest
area under the curve for body mass index (area = 0.787). Body mass index had the
best discriminatory power. Waist to hip ratio was not a sensitive marker
especially for females. CONCLUSIONS: A strong association between obesity indices
and diabetes was identified. BMI and WC could be used in clinical practice for
suggesting life style modifications.
PMID- 28515634
TI - Difference in quality of life and associated factors among the elderly in rural
Vietnam.
AB - BACKGROUND: In Vietnam today, many generations remain living together in a
family. With escalating urbanization and population aging, mental health
disorders and the quality of life (QoL) among the elderly are gradually
presenting themselves as of great concern. The objective of this study was to
examine gender differences in QoL and some associated factors among the elderly
in rural Vietnam using the QoL scale of WHO (WHOQOL-BREF). METHODS: A cross
sectional study using quantitative methods. RESULTS AND CONCLUSIONS: The
proportion of the elderly men having higher level of QoL in physical health,
psychological health and environment was higher than that of their women
counterparts. Reversely, of those having medium and lower QoL, females made up a
larger proportion than males. The overall QoL score in elderly men (75.32) was
higher than that of women (72.32) and the same pattern was witnessed in all four
domains of QoL. While higher QoL in elderly men was significantly correlated with
5 factors, aged >= 80 years, following Buddhism and Christianity, having better
connection and without illness in the past 6 months, these among female
counterparts are aged >= 80 years, completing secondary level or above, having
medium and high socioeconomic status and without illness in the last 6 months.
PMID- 28515636
TI - Optic cup segmentation: type-II fuzzy thresholding approach and blood vessel
extraction.
AB - We introduce here a new technique for segmenting optic cup using two-dimensional
fundus images. Cup segmentation is the most challenging part of image processing
of the optic nerve head due to the complexity of its structure. Using the blood
vessels to segment the cup is important. Here, we report on blood vessel
extraction using first a top-hat transform and Otsu's segmentation function to
detect the curves in the blood vessels (kinks) which indicate the cup boundary.
This was followed by an interval type-II fuzzy entropy procedure. Finally, the
Hough transform was applied to approximate the cup boundary. The algorithm was
evaluated on 550 fundus images from a large dataset, which contained three
different sets of images, where the cup was manually marked by six
ophthalmologists. On one side, the accuracy of the algorithm was tested on the
three image sets independently. The final cup detection accuracy in terms of area
and centroid was calculated to be 78.2% of 441 images. Finally, we compared the
algorithm performance with manual markings done by the six ophthalmologists. The
agreement was determined between the ophthalmologists as well as the algorithm.
The best agreement was between ophthalmologists one, two and five in 398 of 550
images, while the algorithm agreed with them in 356 images.
PMID- 28515635
TI - Changing the smoking habit: prevalence, knowledge and attitudes among Umbrian
hospital healthcare professionals.
AB - BACKGROUND: Health care professionals should work against smoking habit to
promote a correct life style. This study aimed to evaluate smoking prevalence and
attitudes towards tobacco among Umbrian hospital professionals in a period
between 2006 and 2015, since the approbation of the law that ban smoking in
hospitals and all public areas in 2003. METHODS: A cross-sectional study was
carried out using a questionnaire administered in 2006, 2011 and 2015 to
healthcare professionals. It consists of 53 multiple-choice questions. Potential
predictors of current smoking habits were evaluated using univariate and
multivariate logistic regression. RESULTS: The sample included 475 healthcare
professionals. Current smokers constituted 34.53% of the sample and no
significant difference (p = 0.257) emerged in prevalence over time (33.74% in
2006; 36.02% in 2011 and 33.77% in 2015). The risk of being a smoker increased by
not considering the smoking habit as the main cause of preventable deaths (OR =
2.25; 95% CI: 1.47- 3.45). The strongest risk factor, which was significant in
both models (p < 0.01), was being against the "No Smoking" law (OR = 18.90; 95%
CI: 2.43-147.71; adjusted OR = 22.10; 95% CI: 1.85-264.78). CONCLUSIONS: The
hospital staff has higher prevalence of smoking than the general population. The
No Smoking law alone has been shown to be inadequate. Effective results can be
achieved only by a common strategy and shared intervention programmes that are
based on a workplace health promotion strategy. That for the moment has
demonstrated to give interesting outcomes in modifying deep-rooted behaviour
patterns.
PMID- 28515637
TI - Ultrasound biomicroscopy value in evaluation of restoration of ciliary muscles
contractility after cataract extraction.
AB - PURPOSE: To assess the changes in the contractility of the ciliary muscle in eyes
with presbyopia before and after phacoemulsification and intracapsular lens
implantation using ultrasound biomicroscopy (UBM). PATIENTS AND METHODS: This
prospective study included 50 eyes of 30 consecutive subjects operated at the
Department of Ophthalmology. Patients with any ocular disorder affecting visual
acuity, corneal surface irregularities, had posterior capsular perforation or
intensive postoperative corneal edema, or were <35 years of age, were excluded. A
clear corneal phacoemulsification and posterior chamber intraocular lens were
implanted. UBM was performed with and without instilling 2% pilocarpine. Ciliary
body axial length (CBAXL), anterior chamber depth, and angle were measured before
and 1 month after surgery. RESULTS: The CBAXL showed a greater contractile
shortening (P<0.5), with centripetal, contractile shift of ciliary muscle mass.
CONCLUSION: After phacoemulsification and intracapsular lens implantation,
ultrasonic biomicroscopy showed significant centripetal movement of the ciliary
body compared with that before surgery. This shows that a lenticular sclerotic
component may influence both lens movement and the contractility of the ciliary
muscle and is believed to be related to the presbyopia.
PMID- 28515638
TI - Fatty Acid Profiles, Meat Quality, and Sensory Palatability of Grain-fed and
Grass-fed Beef from Hanwoo, American, and Australian Crossbred Cattle.
AB - Fatty acid profiles in relation to meat quality traits and sensory palatability
of grain-fed and grass-fed beef from Hanwoo, American, and Australian crossbred
cattle were examined in this study. There were significant (p<0.001) differences
in fat content and fatty acid compositions between grain-fed and grass-fed beef.
Grain-fed Hanwoo had significantly (p<0.001) lower saturated fatty acid (SFA)
proportion but higher monounsaturated fatty acid (MUFA) proportion compared to
grass-fed cattle. The proportion of oleic acid in grain-fed Hanwoo was
significantly (p<0.001) higher than that in grass-fed Hanwoo, Australian
crossbred, or American crossbred cattle. Grain-fed Hanwoo had significantly
(p<0.001) lower percentages of drip loss and cooking loss compared to other
cattle. Overall palatability panel scores of grain-fed cattle were significantly
(p<0.001) higher than those of grass-fed cattle. Consequently, sensory overall
palatability was negatively correlated with proportions of SFA and
polyunsaturated fatty acid (PUFA), but positively correlated with the proportion
of MUFA. In particular, the proportion of oleic acid was strongly and positively
correlated with fat content (r=0.91, p<0.001) and overall palatability (r=0.92,
p<0.001). These results implied that high-concentrate grain-fed could increase
intramuscular fat (IMF) content and the proportion of oleic acid, thus increasing
the sensory palatability of Hanwoo beef.
PMID- 28515639
TI - Influence of Adding Recovered Protein from Processing Wastewater on the Quality
of Mechanically Separated Chicken Meat Surimi Like-Material.
AB - Functional and nutritional soluble proteins can be recovered from surimi (and
surimi-like material) processing wastewater, reducing environmental problems and
the cost of an irresponsible waste disposal. Recovered proteins may be added back
at a low percentage to surimi products. The aim of this work was to evaluate the
effect of the addition of soluble recovered proteins (RP), obtained from
mechanically separated chicken meat surimi-like material (MSCM-SLM) processing
wastewater by acidic pH-shifting, on the composition and texture of RP-MSCM-SLM,
with RP contents of 0, 10, 20 and 30% (w/w) in the mixture. For that, proximate
composition and gel properties were evaluated. The fat content of the MSCM-SLM
was significantly reduced to 11.98% and protein increased to 83.64% (dry basis)
after three washing cycles. The addition of 30% RP in the MSCM-SLM significantly
augmented the protein content to 93.45% and reduced fat content from to 2.78%. On
the other hand, the addition of RP was responsible for a drastic decrease in
texture parameters, reaching 252.36 g, 185.23 g.cm, and 6.97 N for breaking
force, gel strength and cutting strength, respectively, when 30% of RP was
included in the MSCM-SLM. It was concluded that the obtained intermediary product
(RP-MSCM-SLM) is a good option to applications in processed meat products where
high texture parameters are dispensable, e.g., emulsified inlaid frankfurter-type
sausages, but high protein content and low fat content desired.
PMID- 28515640
TI - Carcass and Meat Characteristics and Gene Expression in Intramuscular Adipose
Tissue of Korean Native Cattle Fed Finishing Diets Supplemented with 5% Palm Oil.
AB - We hypothesized that supplementing finishing diets with palm oil would promote
adipogenic gene expression but depress stearoyl-CoA desaturase (SCD) gene
expression in intramuscular (i.m.) adipose tissues of Hanwoo steers during
fattening period (from 16 to 32 mon of age). Fourteen Hanwoo steers were allotted
randomly to 2 groups of 7 steers based on initial BW and fed either a basal diet
(control) or the basal diet supplemented with 5% palm oil (BDSP). At slaughter,
i.m. adipose tissue was harvested for analysis of adipogenic gene expression and
fatty acid composition. There were no differences in BW or average daily gain
between treatment groups. Supplemental palm oil had no effect on carcass quality
traits (carcass weight, backfat thickness, loin muscle area, or marbling scores)
or meat color values. Palm oil increased (p<0.05) expression of AMP-activated
protein kinase-alpha and peroxisome proliferator-activated receptor-gamma, but
decreased (p<0.05) CAAT/enhancer binding protein-beta gene expression and tended
to decrease stearoyl-CoA desaturase gene expression in i.m. adipose tissue. Palm
oil increased total i.m. polyunsaturated fatty acids (p<0.05) compared to the
control i.m. adipose tissue, but had no effect on saturated or monounsaturated
fatty acids. Although there were significant effects of supplemental palm oil on
i.m. adipose tissue gene expression, the absence of negative effects on carcass
and meat characteristics indicates that palm oil could be a suitable dietary
supplement for the production of Hanwoo beef cattle.
PMID- 28515641
TI - Molecular Typing and Antimicrobial Susceptibility of Staphylococcus aureus
Strains Isolated from Raw Milk, Cheese, Minced Meat, and Chicken Meat Samples.
AB - The objectives of this study were: i) to detect the presence of Staphylococcus
aureus and methicillin-resistant S. aureus (MRSA) in raw milk, cheese, beef
minced meat, and chicken meat samples; ii) to evaluate the antimicrobial
susceptibility of the isolates; and iii) to determine clonal relation among the
isolates by using pulsed-field gel electrophoresis (PFGE) method. Therefore, a
total of 160 food samples were randomly collected between August 2014 and May
2015 in Hatay province, located in the southern Turkey. Twenty (12.5%) of the
samples were found to be contaminated with S. aureus. A total of 40 isolates from
the 20 positive samples were confirmed to be S. aureus by multiplex PCR based on
16S rRNA and nuc gene. The mec A gene was not detected in any of the S. aureus
strains. In the present study, 39 out of 40 (97.5%) isolates were found to be
resistant to one or more antibiotics. All of isolates were susceptible to
gentamicin, oxacillin, and vancomycin. The highest resistance rate was detected
in penicillin (95%) and ampicillin (92.5%), followed by tetracycline (30%),
erythromycin (20%), ciprofloxacin (12.5%). Nine major patterns were determined by
PFGE. In 6 of these patterns, thirty-six strains (90%) had identical PFGE
profiles.
PMID- 28515642
TI - Physicochemical and Functional Characterization of Blue-Shelled Eggs in Korea.
AB - The aim of this study was to compare the quality and physicochemical
characteristics of blue-shelled eggs (BE) and conventional eggs (CE). Proximate
composition, quality, pH value, shell color, collagen content, fatty acid
composition, total cholesterol, alpha-glucosidase inhibition activity, and
antioxidation activity were determined. The proximate composition, general
qualities, and pH values of CE and BE showed no significant differences, except
in moisture composition, weight, and shell thickness. Moisture content and weight
of BE were significantly lower than those of CE. However, shell thickness and
weight of BE were higher than those of CE (p<0.05). Lightness of BE was
significantly higher than that of CE (85.20 vs. 58.80), while redness (a*) and
yellowness (b*) of BE were lower than those of CE (a*: -4.75 vs. 14.20; b*: 10.45
vs. 30.63). The fatty acid [C18:1n7 (cis-vaccenic acid) and C18:3n6 (gamma
linolenic acid)] contents of BE were significantly higher than those of CE. The
total cholesterol contents of BE and CE were similar. DPPH radical scavenging
activity of BE was significantly higher than that of CE (40.78 vs. 35.35).
Interestingly, alpha-glucosidase inhibition activity of whole egg and egg yolk in
BE (19.27 and 36.06) was significantly higher than that of whole egg and egg yolk
in CE (13.95 and 32.46). This result indicated that BE could potentially be used
as a functional food material. Further studies are required to evaluate the
specific compounds that affect functional activity.
PMID- 28515643
TI - Quality of Frozen Pork from Pigs Fed Diets Containing Palm Kernel Meal as an
Alternative to Corn Meal.
AB - The objective of this study was to evaluate the effect of different levels of
palm kernel meal (PKM), an alternative to corn, on the quality of pork. A total
of 72 crossbred pigs ([Yorkshire * Landrace] * Duroc) were assigned into four
dietary treatments (PKM level of 0, 4, 8, or 12%). After 12 wk, one pig of median
weight in each pen was selected and slaughtered to analyze meat quality. The
color, free radical scavenging activity, lipid oxidation, texture, composition of
fatty acids, and sensory qualities of pork loin were evaluated post slaughter.
When the levels of PKM in the diet increased, the L*-value of pork loin
decreased, whereas a*-value and total saturated fatty acids increased. 2
Thiobarbituric acid reactive substance (TBARS) values of pork loin were lower in
groups treated with 8 and 12% PKM than in the control group at day 0; this
difference, however, was not observed at day 3 and 7. The results of texture
analysis showed that increasing the PKM ratio decreased hardness, chewiness, and
springiness at day 7. The sensory test, however, indicated no differences between
the control and treated groups. These findings show that finisher pigs could
tolerate PKM as a replacement for corn; PKM did not negatively affect the quality
of pork, indicating that it can be utilized as feed.
PMID- 28515644
TI - Effects of Bundle Type and Substitution with Spent Laying Hen Surimi on Quality
Characteristics of Imitation Crabsticks.
AB - The purpose of this study was to evaluate the effects of bundle type (BT) and
substitution with spent laying hen (SH) surimi on quality characteristics of
imitation crabsticks made from Alaska Pollack (AP) during 6 wk of cold storage.
Diagonally bundled samples had poorer gel characteristics and more lipid
oxidation when compared with straight bundled ones (p<0.05). The color of
diagonally bundled imitation crabsticks deteriorated with storage time (p<0.01).
However, BT did not affect sensory characteristics (p>0.05). SH substitution had
an effect on most quality characteristics of imitation crabsticks; darker and
poorer gel characteristics were observed and its effect on sensory evaluation was
seen at the initial storage. Thus, BT and SH substitution can be considered to
have a slight effect on eating quality of imitation crabsticks, despite their
negative effects on color, gel characteristics, and lipid oxidation.
PMID- 28515645
TI - Effect of Abalone Hydrolysates Encapsulated by Double Emulsion on the
Physicochemical and Sensorial Properties of Fresh Cheese.
AB - The intake of dietary salt through food now exceeds current nutritional
recommendations and is thought to have negative effects on human health, such as
the increasing prevalence of hypertension. This study was performed to
investigate whether W1/O/W2 double emulsions can be used to enhance the saltiness
of cheese without increasing the salt content (W1 is distilled water or 1%
abalone hydrolysate, and W2 is 1% NaCl or 1% abalone hydrolysate + 1% NaCl
solution). We also investigated the effect of adding abalone hydrolysate to the
double emulsion as a saltiness enhancer. The cheeses were physico-chemically
evaluated to determine curd yield, pH value, moisture content, color, texture,
salt release rate, and sensory properties. No significant differences were
observed in curd yield, pH value, moisture content, lightness, or redness between
the cheeses made with and without the double emulsion. However, in the evaluation
of salt release rate, fresh cheese made with double emulsion (W1 = distilled
water, W2 = 1% NaCl + 1% abalone hydrolysate) was detected earlier than the
control or the other treatments. In the sensory evaluation, fresh cheese made
with the double emulsion showed higher scores for saltiness and overall
preference than the control or the other treatments. We concluded that abalone
hydrolysate encapsulated in a double emulsion (W1 is water and W2 is abalone
hydrolysate and NaCl solution) could enhance the saltiness of fresh cheese while
maintaining the same salt concentration, without altering its physical
properties.
PMID- 28515647
TI - Comparative Study on Compositions and Functional Properties of Porcine, Chicken
and Duck Blood.
AB - Hematological, chemical and functional characteristics of porcine, chicken and
duck blood were evaluated. A porcine blood sample showed the most abundant red
blood cell, hemoglobin concentration, packed cell volume and plasma protein
content as well as its freeze-dried blood possessed the highest contents of
protein, fat, Cu and Cr with the highest percentage of heme iron (p<0.05). Unlike
porcine blood, chicken blood showed a well balance in some essential amino acids,
specifically for a higher isoleucine content (p<0.05). Furthermore, it possessed
the highest contents of carbohydrate, Zn and non-heme iron (p<0.05). The most
rapid response to form a strong gel, especially at 70 degrees C and 80 degrees C,
was found in chicken blood, followed by duck and porcine blood, respectively. The
result of emulsion activity index (EAI) and emulsion stability index (ESI) at the
low protein concentration indicated that chicken blood had the most superior
emulsion properties (p<0.05). Regarding duck blood, it exhibited the highest
content of Mg and Mn (p<0.05). Moreover, duck blood had similar foaming
properties to porcine blood in which they showed higher values than chicken blood
(p<0.05). Specific characteristics of blood were therefore diminished by animal
species in which this information could be used as food supplementation or
product development based on their potential applications.
PMID- 28515646
TI - Lotus (Nelumbo nucifera) Rhizome as an Antioxidant Dietary Fiber in Cooked
Sausage: Effects on Physicochemical and Sensory Characteristics.
AB - The objective of this study was to determine the physicochemical and sensory
properties of cooked emulsion sausages containing different levels of lotus
rhizome powder (0, 1, 2, and 3%, based on total weight). Lotus rhizome powder had
no significant (p>0.05) impact on pH, moisture, protein, or ash content of
sausage. However, fat content was slightly but significantly (p<0.05) decreased
when the level of lotus rhizome powder was increased in the sausages. The
addition of lotus rhizome powder to sausages at over 1% resulted in significantly
(p<0.05) darker and less red color of cooked sausage compared to control.
Increase in lotus rhizome level slightly improved the emulsion stability and
apparent viscosity. Significant (p<0.05) reduction in cooking loss was observed
when more than 1% of lotus rhizome powder was added to sausages. The textural
properties of sausages were unaffected by the inclusion of lotus rhizome except
for springiness and chewiness. On the manufacture day, control sausage had
significantly (p<0.05) higher TBARS value than treatments. Regarding sensory
characteristics, increased levels of lotus rhizome powder decreased (p<0.05)
color and juiciness scores. However, cooked sausages exhibited similar overall
acceptability regardless of the level of lotus rhizome powder added to sausages.
Therefore, lotus rhizome powder, an antioxidant dietary fiber, could be used as
an effective natural ingredient in meat products for the development of healthier
and functional food.
PMID- 28515648
TI - Evaluation of Antioxidative Activity of Various Levels of Ethanol Extracted
Tomato Powder and Application to Pork Patties.
AB - This study was performed to evaluate antioxidant activity of tomato powder
extracted by various concentrations of ethanol (0, 25, 50, 75, 100%) and to
evaluate the physicochemical properties and antioxidant activities of pork
patties with ethanol extracted tomato (EET) powder. No differences in the
contents of total of individual phenolic compounds including gallic acid and
catechin, were observed among the treatments (p>0.05). Among the various
concentrations, 50% and 75% EET powder showed the highest free radical scavenging
and iron chelating activities (p<0.05). Lipid peroxidation was retarded in
linoleic acid emulsion with the addition of 50% and 75% EET powder (0.1%). Based
on the model study, five pork patties were actually manufactured; control patty,
reference patty with 0.01% of butylated hydroxytoluene, patty with 1% of water
extracted tomato (WET), and patties with 0.5 and 1.0% of EET. Addition of 1% WET
and EET decreased pH value, and increased redness values of pork patties, as
compared to the control (p<0.05). Pork patties with WET (1.0%) and EET (0.5% and
1.0%) had lower 2-thiobarbituric acid reactive substances values compared with
control patties after 7 d of storage (p<0.05). Pork patties containing EET powder
showed lower total bacterial and Enterobacteriaceae counts than control patties
(p<0.05). In conclusion, WET and EET (50%) could be used as a natural antioxidant
and antimicrobial agent in meat products.
PMID- 28515649
TI - Effect of Persimmon Peel (Diospyros kaki Thumb.) Extracts on Lipid and Protein
Oxidation of Raw Ground Pork During Refrigerated Storage.
AB - The inhibition effect of persimmon peel extracts (PPE) (0.05(PPE-0.05), 0.1(PPE
0.1), and 0.2 g(PPE-0.2) per meat sample) on lipid and protein oxidation of pork
patties during chilled storage for 12 days were investigated and compared to
ascorbic acid (As-0.05) and butylhydroxytoluene (BHT) (BHT-0.01). The meat
samples treated with PPE had greater (p<0.05) a* values comparing control in raw
pork patties meat from day 4 of storage. The addition of PPE at all
concentrations on meat samples effectively inhibited the formation of oxidation
products as shown by decreasing conjugated dienes (CD), peroxide values (POVs),
thiobarbituric acid reaction substances (TBARS), and carbonyl content during
chilled storage for 12 d. The PPE-0.2 and BHT-0.01 had the lowest in decrease
rate of free thiol content (0.24 and 0.22 times) during chilled storage.
Therefore, results of this study suggest that PPE can be considered a potential
antioxidant against lipid and protein oxidation of raw meat products.
PMID- 28515650
TI - Prevalence and Comparing of Some Microbiological Properties, Somatic Cell Count
and Antibiotic Residue of Organic and Conventional Raw Milk Produced in Turkey.
AB - The aim of this study was to investigate the effects of production systems and
milk collection periods on the somatic cell count (SCC), some microbiological
properties, total aerobic mesophilic bacteria (TAMB), coliform, Staphylococcus
aureus (S. aureus), yeast and mould) and antibiotic residue of milk; in Turkey.
Milk samples were collected from 9 conventional farms and 9 organic farms during
one year time, at six different months (December 2013 to October 2014), and all
farms were selected from the same geographical locations. All organically managed
farms had organic production certificates given by the Republic of Turkey
Ministry of Food, Agriculture and Livestock. The count of TAMB, coliform, and
coagulase positive S. aureus were affected by production systems at the level of
p<0.01; yeast and mold, and somatic cell count (SCC) were affected at the level
of p<0.05. But, differences according to months were statistically significant
only on TAMB (p<0.01) and coliform (p<0.05) counts. The general means of TAMB,
coliform and yeast and mould counts of the organic milk (OM) were significantly
lower (p<0.05), while the general means of SCC and coagulase positive S. aureus
count of the OM was significantly higher (p<0.05) compared to conventional milk
(CM). Antibiotic residue was determined in one of the CM sample and in two of the
OM samples. Our study is the first research that compared conventional and
organic milk in Turkey. This study indicated that the microbiological quality of
OM was the higher in terms of TAMB, coliform and yeast and mould, whereas was the
lower in relation to SCC and coagulase positive S. aureus counts. But, the
quality of both milk types should be improved.
PMID- 28515651
TI - Effect of Gleditsia sinensis Lam. Extract on Physico-Chemical Properties of
Emulsion-Type Pork Sausages.
AB - This study was performed to investigate the effect of Gleditsia sinensis Lam.
extract on the physicochemical properties of emulsion-type pork sausages during
storage at 10 degrees C for 4 wk. Treatments were as follows: (C, control; T1,
sodium ascorbate 0.05%; T2, Gleditsia sinensis Lam. 0.05%; T3, Gleditsia sinensis
Lam. 0.1%; T4, Gleditsia sinensis Lam. 0.2%; T5, Gleditsia sinensis Lam. 0.1% +
sodium ascorbate 0.05%). The values of pH, moisture content, lightness, redness,
and sensory attributes were all significantly decreased, while the yellowness,
chroma, hue angle, and texture properties were increased during storage with
increase of the Gleditsia sinensis Lam. extract added. In addition, the
antioxidant activity and antimicrobial activity in the sausages displayed
significant increases (p<0.05). Therefore, although it was concluded that the
addition of Gleditsia sinensis Lam. extract is not effective for improvement of
the physical properties compared to chemical additives in sausages, it could be
applied to meat products as a natural preservatives.
PMID- 28515652
TI - Effects of Pre-Converted Nitrite from Red Beet and Ascorbic Acid on Quality
Characteristics in Meat Emulsions.
AB - We investigated the effects of fermented red beet extract and ascorbic acid on
color development in meat emulsions. The pH of meat emulsions containing red beet
extract decreased with an increase in the amount of extract added. The redness of
the treated meat emulsions was higher than that of the control with no added
nitrite or fermented red beet extract (p<0.05), though the redness of the meat
emulsions treated with fermented red beet extract only was lower than in that
treated with both fermented red beet extract and ascorbic acid (p<0.05). The
highest VBN, TBARS, and total viable count values were observed in the control,
and these values in the meat emulsions treated with fermented red beet extract
were higher than in that treated with both fermented red beet extract and
ascorbic acid (p<0.05). E. coli and coliform bacteria were not found in any of
the meat emulsions tested. Treatment T2, containing nitrite and ascorbic acid,
had the highest overall acceptability score (p<0.05); however, there was no
significant difference between the T2 treatment and the T6 treatment, which
contained 10% pre-converted nitrite from red beet extract and 0.05% ascorbic acid
(p>0.05). The residual nitrite content of the meat emulsions treated with
ascorbic acid was lower than in those treated without ascorbic acid (p<0.05).
Thus, the combination of fermented red beet extract and ascorbic acid could be a
viable alternative to synthetic nitrite for the stability of color development in
meat emulsions.
PMID- 28515653
TI - Assessment of Microbial and Radioactive Contaminations in Korean Cold Duck Meats
and Electron-Beam Application for Quality Improvement.
AB - Animal-origin food products pose serious threat to public food safety due to high
microbial loads. The microbial and radioactive contaminations in commercial cold
duck meat products were evaluated. Ten different lots of commercial samples (C1
C10) were classified based on type and smoking process. All samples were highly
contaminated (< 4-7 Log CFU/g) with total aerobic bacteria (TAB), yeasts and
molds (Y&M), and 7 samples (C1-C7) were positive for coliforms. Furthermore,
three samples were contaminated with Listeria monocytogenes (C4-C6) and one with
Salmonella typhimurium (C6). No radionuclides (131I, 137Cs, and 134Cs) were
detected in any sample. The results of DEFT (direct epifluorescent filter
technique)/APC (aerobic plate count), employed to screen pre-pasteurization
treatments of products, indicated that smoked samples were positive showing
DEFT/APC ratios higher than 4. Notably, the samples showed a serious threat to
microbial safety, thus were irradiated with electron-beam (e-beam). The D10
values for S. typhimurium and L. monocytogenes were 0.65 and 0.42 kGy,
respectively. E-beam application at 3 and 7 kGy resulted in reduction of initial
TAB, Y&M, and coliform populations by 3 and 6 log cycles, respectively. Thus, e
beam was proven to be a good decontamination approach to improve the hygiene of
cold duck meat.
PMID- 28515654
TI - Qualitative Characteristics and Determining Shelf-Life of Milk Beverage Product
Supplemented with Coffee Extracts.
AB - This study was conducted to establish the shelf-life of a milk beverage product
supplemented with coffee extracts. Qualitative changes including peroxide value
(PV), microorganism content, caffeine content, and sensory evaluation were
measured periodically in beverages kept at 10, 20, and 30 degrees C for 8 wk.
Lipid oxidation of the product was measured by peroxide value analysis, and
apparent changes were observed during a 4 wk storage period. Caffeine analysis
revealed that the changes in caffeine content were negligible during the storage
period. Total aerobic bacteria, Escherichia coli, yeast, and mold were not
detected in the products during an 8 wk storage period. Sensory evaluation
revealed that after 4 wk of storage overall acceptance was less than 3 points on
a 5-point scale. In this study, PV was used as an indicator of the shelf-life of
the milk beverage product. PV analysis revealed that a value of 20 meq/kg was the
end of the shelf-life using the Arrhenius equation and the accelerated shelf-life
test (ASLT). Assuming that the beverages are kept at 4 degrees C during
distribution, calculation of when the PV reached the quality limit point (20
meq/kg) was done with the equation ln(PV) = 0.3644X - 2.21834 and, using that
equation, PV = e0.3644X-2.21834 was calculated. Therefore, 14.3086 wk was
determined to be the shelf-life of the milk beverage supplemented with coffee
when stored at 4 degrees C.
PMID- 28515655
TI - Effect of Calcium Lactate on Physico-Chemical Characteristics of Shank Bone
Extract.
AB - This study was conducted to develop calcium-fortified shank bone extract (SBE)
and to determine the effect of adding calcium lactate on physico-chemical
characteristics of SBE during cold storage. The following five experiment groups
were used: Control (0%, no addition), T1 (0.05% calcium lactate), T2 (0.1%
calcium lactate), T3 (0.5% calcium lactate), and T4 (1% calcium lactate). When
the concentration of calcium lactate added to the SBE was increased, the pH,
redness, and yellowness values were significantly reduced, whereas the salinity,
sugar content, and turbidity of SBE were significantly increased. Sensory
parameters such as aroma, flavor, and overall acceptability in the control, T1,
and T2 had similar scores. The TBARS values of SBE was significantly increased
when 1% of calcium lactate was added, and the VBN values of SBE with calcium
lactate at day 7 were higher than that of control (p<0.05). However, the addition
of calcium lactate showed an inhibition effect on the growth of total microbial
counts in SBE until 4 d of storage. The calcium content of SBE was increased by
the addition of calcium lactate in a dose-dependently manner. The proper addition
level of calcium lactate in the SBE was determined to be 0.1%.
PMID- 28515657
TI - Symposium on visualization in high-performance computing at SIGGRAPH Asia 2015.
PMID- 28515656
TI - Isolation and Characterization of Listeria phages for Control of Growth of
Listeria monocytogenes in Milk.
AB - In this study, two Listeria bacteriophages, LMP1 and LMP7, were isolated from
chicken feces as a means of biocontrol of L. monocytogenes. Both bacteriophages
had a lytic effect on L. monocytogenes ATCC 7644, 15313, 19114, and 19115. Phages
LMP1 and LMP7 were able to inhibit the growth of L. monocytogenes ATCC 7644 and
19114 in tryptic soy broth at 10 degrees C and 30 degrees C. Nevertheless, LMP1
was more effective than LMP7 at inhibiting L. monocytogenes ATCC 19114. On the
contrary, LMP7 was more effective than LMP1 at inhibiting L. monocytogenes ATCC
7644. The morphology of LMP1 and LMP7 resembled that of members of the
Siphoviridae family. The growth of L. monocytogenes ATCC 7644 was inhibited by
both LMP1 and LMP7 in milk; however, the growth of L. monocytogenes ATCC 19114
was only inhibited by LMP1 at 30 degrees C. The lytic activity of bacteriophages
was also evaluated at 4 degrees C in milk in order to investigate the potential
use of these phages in refrigerated products. In conclusion, these two
bacteriophages exhibit different host specificities and characteristics,
suggesting that they can be used as a component of a phage cocktail to control L.
monocytogenes in the food industry.
PMID- 28515658
TI - Flow visualisation of a normal shock impinging over a rounded contour bump in a
Mach 1.3 free-stream.
AB - ABSTRACT: An experimental study has been conducted to visualise the instantaneous
streamwise and spanwise flow patterns of a normal shock wave impinging over a
rounded contour bump in a Mach 1.3 free-stream. A quartz-made transparent shock
generator was used, so that instantaneous images could be captured during the oil
flow visualisation experiments. Fluorescent oil with three different colours was
used in the surface oil-flow visualisation experiment to enhance the
visualisation of flow mixing and complicated flow features that present in the
flow field. Experimental data showed that the rounded contour bump could split
the impinging normal shock wave into a or a series of lambda-shaped shock wave
structure(s). In addition, it was found that the flow pattern and the shock wave
structures that appeared over the rounded contour bump depended highly on the
impinging location of the normal shock wave. The flow pattern shown in this study
agreed with the findings documented in literature. Moreover, it was observed from
the instantaneous oil streaks that the normal shock impinging location also
affected the size and the formation location of the spanwise counter-rotating
vortices downstream of the bump crest. Finally, it was concluded that the
terminating shock could distort the oil streaks that left over the surface of the
contour bump. Therefore, the use of the transparent normal shock wave generator
is recommended when conducting experiments with normal shock wave impingement
involved. GRAPHICAL ABSTRACT:
PMID- 28515659
TI - The flow separation delay in the boundary layer by induced vortices.
AB - ABSTRACT: A series of experiments involving the particle image velocimetry
technique are carried out to analyse the quantitative effectiveness of the
synthesized vortical structures towards actual flow separation control. The
streamwise vortices are synthesized from the synthetic jet actuator and
introduced into the attached and separating boundary layer developed on the flat
plate surface. Two types of actuators with different geometrical set-ups are used
to analyse the evolution of vortical structures in the near wall region and their
impact towards achieving separation delay in the boundary layer. First, a single
circular jet is synthesized by varying actuator operating parameters and issued
into the boundary layer to evaluate the dynamics of the interaction between the
vortical structures and the near wall low momentum fluid in the separated region.
Second, an array of jets has been issued into the artificially separated region
to assess the effectiveness of various vortical structures towards achieving the
reattachment of the separated flow in the streamwise direction. GRAPHICAL
ABSTRACT:
PMID- 28515661
TI - Improving Large Area Population Mapping Using Geotweet Densities.
AB - Many different methods are used to disaggregate census data and predict
population densities to construct finer scale, gridded population data sets.
These methods often involve a range of high resolution geospatial covariate
datasets on aspects such as urban areas, infrastructure, land cover and
topography; such covariates, however, are not directly indicative of the presence
of people. Here we tested the potential of geo-located tweets from the social
media application, Twitter, as a covariate in the production of population maps.
The density of geo-located tweets in 1x1 km grid cells over a 2-month period
across Indonesia, a country with one of the highest Twitter usage rates in the
world, was input as a covariate into a previously published random forests-based
census disaggregation method. Comparison of internal measures of accuracy and
external assessments between models built with and without the geotweets showed
that increases in population mapping accuracy could be obtained using the
geotweet densities as a covariate layer. The work highlights the potential for
such social media-derived data in improving our understanding of population
distributions and offers promise for more dynamic mapping with such data being
continually produced and freely available.
PMID- 28515660
TI - Environmental factors associated with the distribution of visceral leishmaniasis
in endemic areas of Bangladesh: modeling the ecological niche.
AB - BACKGROUND: Visceral leishmaniasis (VL) is a parasitic infection (also called
kala-azar in South Asia) caused by Leishmania donovani that is a considerable
threat to public health in the Indian subcontinent, including densely populated
Bangladesh. The disease seriously affects the poorest subset of the population in
the subcontinent. Despite the fact that the incidence of VL results in
significant morbidity and mortality, its environmental determinants are
relatively poorly understood, especially in Bangladesh. In this study, we have
extracted a number of environmental variables obtained from a range of sources,
along with human VL cases collected through several field visits, to model the
distribution of disease which may then be used as a surrogate for determining the
distribution of Phlebotomus argentipes vector, in hyperendemic and endemic areas
of Mymensingh and Gazipur districts in Bangladesh. The analysis was carried out
within an ecological niche model (ENM) framework using a maxent to explore the
ecological requirements of the disease. RESULTS: The results suggest that VL in
the study area can be predicted by precipitation during the warmest quarter of
the year, land surface temperature (LST), and normalized difference water index
(NDWI). As P. argentipes is the single proven vector of L. donovani in the study
area, its distribution could reasonably be determined by the same environmental
variables. The analysis further showed that the majority of VL cases were located
in mauzas where the estimated probability of the disease occurrence was high.
This may reflect the potential distribution of the disease and consequently P.
argentipes in the study area. CONCLUSIONS: The results of this study are expected
to have important implications, particularly in vector control strategies and
management of risk associated with this disease. Public health officials can use
the results to prioritize their visits in specific areas. Further, the findings
can be used as a baseline to model how the distribution of the disease caused by
P. argentipes might change in the event of climatic and environmental changes
that resulted from increased anthropogenic activities in Bangladesh and
elsewhere.
PMID- 28515662
TI - TEMPO functionalized C60 fullerene deposited on gold surface for catalytic
oxidation of selected alcohols.
AB - C60TEMPO10 catalytic system linked to a microspherical gold support through a
covalent S-Au bond was developed. The C60TEMPO10@Au composite catalyst had a
particle size of 0.5-0.8 MUm and was covered with the fullerenes derivative of
2.3 nm diameter bearing ten nitroxyl groups; the organic film showed up to 50 nm
thickness. The catalytic composite allowed for the oxidation under mild
conditions of various primary and secondary alcohols to the corresponding
aldehyde and ketone analogues with efficiencies as high as 79-98%, thus giving
values typical for homogeneous catalysis, while retaining at the same time all
the advantages of heterogeneous catalysis, e.g., easy separation by filtration
from the reaction mixture. The catalytic activity of the resulting system was
studied by means of high pressure liquid chromatography. A redox mechanism was
proposed for the process. In the catalytic cycle of the oxidation process, the
TEMPO moiety was continuously regenerated in situ with an applied primary
oxidant, for example, O2/Fe3+ system. The new intermediate composite components
and the final catalyst were characterized by various spectroscopic methods and
thermogravimetry. Graphical abstract?.
PMID- 28515668
TI - Nested soft-collinear subtractions in NNLO QCD computations.
AB - We discuss a modification of the next-to-next-to-leading order (NNLO) subtraction
scheme based on the residue-improved sector decomposition that reduces the number
of double-real emission sectors from five to four. In particular, a sector where
energies and angles of unresolved particles vanish in a correlated fashion is
redundant and can be discarded. This simple observation allows us to formulate a
transparent iterative subtraction procedure for double-real emission
contributions, to demonstrate the cancellation of soft and collinear
singularities in an explicit and (almost) process-independent way and to write
the result of a NNLO calculation in terms of quantities that can be computed in
four space-time dimensions. We illustrate this procedure explicitly in the simple
case of [Formula: see text] gluonic corrections to the Drell-Yan process of
[Formula: see text] annihilation into a lepton pair. We show that this framework
leads to fast and numerically stable computation of QCD corrections.
PMID- 28515664
TI - Search for massive long-lived particles decaying semileptonically in the LHCb
detector.
AB - A search is presented for massive long-lived particles decaying into a muon and
two quarks. The dataset consists of proton-proton interactions at centre-of-mass
energies of 7 and 8 TeV, corresponding to integrated luminosities of 1 and
2[Formula: see text], respectively. The analysis is performed assuming a set of
production mechanisms with simple topologies, including the production of a Higgs
like particle decaying into two long-lived particles. The mass range from 20 to
80 [Formula: see text] and lifetimes from 5 to 100[Formula: see text] are
explored. Results are also interpreted in terms of neutralino production in
different R-Parity violating supersymmetric models, with masses in the 23-198
GeV/[Formula: see text] range. No excess above the background expectation is
observed and upper limits are set on the production cross-section for various
points in the parameter space of theoretical models.
PMID- 28515671
TI - Likelihood analysis of the minimal AMSB model.
AB - We perform a likelihood analysis of the minimal anomaly-mediated supersymmetry
breaking (mAMSB) model using constraints from cosmology and accelerator
experiments. We find that either a wino-like or a Higgsino-like neutralino LSP,
[Formula: see text], may provide the cold dark matter (DM), both with similar
likelihoods. The upper limit on the DM density from Planck and other experiments
enforces [Formula: see text] after the inclusion of Sommerfeld enhancement in its
annihilations. If most of the cold DM density is provided by the [Formula: see
text], the measured value of the Higgs mass favours a limited range of [Formula:
see text] (and also for [Formula: see text] if [Formula: see text]) but the
scalar mass [Formula: see text] is poorly constrained. In the wino-LSP case,
[Formula: see text] is constrained to about [Formula: see text] and [Formula: see
text] to [Formula: see text], whereas in the Higgsino-LSP case [Formula: see
text] has just a lower limit [Formula: see text] ([Formula: see text]) and
[Formula: see text] is constrained to [Formula: see text] in the [Formula: see
text] ([Formula: see text]) scenario. In neither case can the anomalous magnetic
moment of the muon, [Formula: see text], be improved significantly relative to
its Standard Model (SM) value, nor do flavour measurements constrain the model
significantly, and there are poor prospects for discovering supersymmetric
particles at the LHC, though there are some prospects for direct DM detection. On
the other hand, if the [Formula: see text] contributes only a fraction of the
cold DM density, future LHC [Formula: see text]-based searches for gluinos,
squarks and heavier chargino and neutralino states as well as disappearing track
searches in the wino-like LSP region will be relevant, and interference effects
enable [Formula: see text] to agree with the data better than in the SM in the
case of wino-like DM with [Formula: see text].
PMID- 28515675
TI - Utility of intraoral stents in external beam radiotherapy for head and neck
cancer.
AB - AIM: This study aimed to assess the utility and stability of intraoral stent
during intensity-modulated radiation therapy (IMRT). BACKGROUND: The benefits of
intraoral stents in radiotherapy are unclear. MATERIALS AND METHODS: We analyzed
386 setup errors in 12 patients who received IMRT for head and neck cancers
without intraoral stents (intraoral stent [-]) and 183 setup errors in 6 patients
who received IMRT with intraoral stents (intraoral stent [+]). All patients were
matched according to the immobilization method (masks and boards). Setup errors
were measured as the distance from the initial setup based on the marking on the
skin and mask to the corrected position based on bone matching on cone beam
computed tomography. RESULTS: The mean interfractional setup errors in the right
left, craniocaudal, anterior-posterior (AP), and three-dimensional (3D)
directions were -0.33, 0.08, -0.25, and 2.75 mm in the intraoral stent (-) group
and -0.37, 0.24, -0.63, and 2.42 mm in the intraoral stent (+) group,
respectively (P = 0.50, 0.65, 0.01, and 0.02, respectively). The systematic
errors for the same directions were 0.89, 1.46, 1.15, and 0.88 mm in the
intraoral stent (-) group and 0.62, 1.69, 0.68, and 0.56 mm in the intraoral
stents (+) group, respectively. The random errors were 1.43, 1.43, 1.44, and 1.22
mm in the intraoral stent (-) group and 1.06, 1.11, 1.05, and 0.92 mm in the
intraoral stents (+) group, respectively. CONCLUSION: Setup errors can be
significantly reduced in the AP and 3D-directions by using intraoral stents.
PMID- 28515673
TI - Growth of MCF-7 breast cancer cells and efficacy of anti-angiogenic agents in a
hydroxyethyl chitosan/glycidyl methacrylate hydrogel.
AB - BACKGROUND: Breast cancer negatively affects women's health worldwide. The tumour
microenvironment plays a critical role in tumour initiation, proliferation, and
metastasis. Cancer cells are traditionally grown in two-dimensional (2D) cultures
as monolayers on a flat solid surface lacking cell-cell and cell-matrix
interactions. These experimental conditions deviate from the clinical situation.
Improved experimental systems that can mimic the in vivo situation are required
to discover new therapies, particularly for anti-angiogenic agents that mainly
target intercellular factors and play an essential role in treating some cancers.
METHODS: Chitosan can be modified to construct three-dimensional (3D) tumour
models. Here, we report an in vitro 3D tumour model using a hydroxyethyl
chitosan/glycidyl methacrylate (HECS-GMA) hydrogel produced by a series of
chitosan modifications. Parameters relating to cell morphology, viability,
proliferation, and migration were analysed using breast cancer MCF-7 cells. In a
xenograft model, secretion of angiogenesis-related growth factors and the anti
angiogenic efficacy of Endostar and Bevacizumab in cells grown in HECS-GMA
hydrogels were assessed by immunohistochemistry. RESULTS: Hydroxyethyl
chitosan/glycidyl methacrylate hydrogels had a highly porous microstructure,
mechanical properties, swelling ratio, and morphology consistent with a 3D tumour
model. Compared with a 2D monolayer culture, breast cancer MCF-7 cells residing
in the HECS-GMA hydrogels grew as tumour-like clusters in a 3D formation. In a
xenograft model, MCF-7 cells cultured in the HECS-GMA hydrogels had increased
secretion of angiogenesis-related growth factors. Recombinant human endostatin
(Endostar), but not Bevacizumab (Avastin), was an effective anti-angiogenic agent
in HECS-GMA hydrogels. CONCLUSIONS: The HECS-GMA hydrogel provided a 3D tumour
model that mimicked the in vivo cancer microenvironment and supported the growth
of MCF7 cells better than traditional tissue culture plates. The HECS-GMA
hydrogel may offer an improved platform to minimize the gap between traditional
tissue culture plates and clinical applicability. In addition, the anti
angiogenic efficacy of drugs such as Endostar and Bevacizumab can be more
comprehensively studied and assessed in HECS-GMA hydrogels.
PMID- 28515678
TI - Soluble Ectodomain of Neuroligin 1 Decreases Synaptic Activity by Activating
Metabotropic Glutamate Receptor 2.
AB - Synaptic cell adhesion molecules represent important targets for neuronal
activity-dependent proteolysis. Postsynaptic neuroligins (NLs) form trans
synaptic complexes with presynaptic neurexins (NXs). Both NXs and NLs are cleaved
from the cell surface by metalloproteases in an activity-dependent manner,
releasing a soluble extracellular fragment and membrane-tethered C-terminal
fragment. The cleavage of NL1 depresses synaptic transmission, but the mechanism
by which this occurs is unknown. Metabotropic glutamate receptor 2 (mGluR2) are
located primarily at the periphery of presynaptic terminals, where they inhibit
the formation of cyclic adenosine monophosphate (cAMP) and consequently suppress
the release of glutamate and decrease synaptic transmission. In the present
study, we found that the soluble ectodomain of NL1 binds to and activates mGluR2
in both neurons and heterologous cells, resulting in a decrease in cAMP
formation. In a slice preparation from the hippocampus of mice, NL1 inhibited the
release of glutamate from mossy fibers that project to CA3 pyramidal neurons. The
presynaptic effect of NL1 was abolished in the presence of a selective antagonist
for mGluR2. Thus, our data suggest that the soluble extracellular domain of NL1
functionally interacts with mGluR2 and thereby decreases synaptic strength.
PMID- 28515676
TI - Low-Dose Dose-Response for In Vitro Nrf2-ARE Activation in Human HepG2 Cells.
AB - Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-like
factor 2-related factor 2 (Nrf2), and the antioxidant response element (ARE) are
interacting components of a master regulatory signaling pathway that coordinates
redox homeostasis, cytoprotective responses, and shifts in stem cell state. This
study reexamined detailed dose-response (DR) data reported for in vitro Nrf2-ARE
activation in human hepatoblastoma HepG2 cell lines containing either a ARE-bla
or ARE-luc reporter at 12 different concentrations of each of 15 chemicals. The
normalized study data were combined among chemicals exhibiting a positive
response, yielding n = 531 (179) DR data for 9 (7) chemicals using the ARE-bla
(ARE-luc) assay. Three-parameter linear/kth-power regression fits obtained to
each combined set of ARE-bla- or ARE-luc-assay response data provided good fits
(R2 = .99 or .91, respectively, Pfit > .99) that each incorporate a highly
significant negative initial linear slope (P = 4 * 10-5 or .00025) and an overall
J-shaped DR pattern. Results from this reanalysis of high-resolution ARE response
data support the hypothesis that nonlinear ARE-mediated adaptive cellular
responses to oxidative stress are governed by an ultrasensitive molecular switch.
PMID- 28515677
TI - Brain Control of Plasma Cholesterol Involves Polysialic Acid Molecules in the
Hypothalamus.
AB - The polysialic acid (PSA) is a large glycan that is added to cell-surface
proteins during their post-translational maturation. In the brain, PSA modulates
distances between cells and controls the plasticity of the nervous system. In the
hypothalamus, PSA is involved in many aspects of energy balance including food
intake, osmoregulation, circadian rhythm, and sleep. In this work, we
investigated the role of hypothalamic PSA in the regulation of plasma cholesterol
levels and distribution. We report that HFD consumption in mice rapidly increased
plasma cholesterol, including VLDL, LDL, and HDL-cholesterol. Although plasma
VLDL-cholesterol was normalized within the first week, LDL and HDL were still
elevated after 2 weeks upon HFD. Importantly, we found that hypothalamic PSA
removal aggravated LDL elevation and reduced HDL levels upon HFD. These results
indicate that hypothalamic PSA controls plasma lipoprotein profile by
circumventing the rise of LDL-to-HDL cholesterol ratio in plasma during
overfeeding. Although mechanisms by which hypothalamic PSA controls plasma
cholesterol homeostasis remains to be elucidated, these findings also suggest
that low level of hypothalamic PSA might be a risk factor for dyslipidemia and
cardiovascular diseases.
PMID- 28515679
TI - Downregulation of the Repressor Element 1-Silencing Transcription Factor (REST)
Is Associated with Akt-mTOR and Wnt-beta-Catenin Signaling in Prion Diseases
Models.
AB - Prion diseases are a group of infectious diseases characterized by multiple
neuropathological changes, yet the mechanisms that preserve function and protect
against prion-associated neurodegeneration are still unclear. We previously
reported that the repressor element 1-silencing transcription factor (REST)
alleviates neurotoxic prion peptide (PrP106-126)-induced toxicity in primary
neurons. Here we confirmed the findings of the in vitro model in 263K infected
hamsters, an in vivo model of prion diseases and further showed the relationships
between REST and related signaling pathways. REST was depleted from the nucleus
in prion infected brains and taken up by autophagosomes in the cytoplasm, co
localizing with LC3-II. Importantly, downregulation of the Akt-mTOR and at least
partially inactivation of LRP6-Wnt-beta-catenin signaling pathways correlated
with the decreased levels of REST in vivo in the brain of 263K-infected hamsters
and in vitro in PrP106-126-treated primary neurons. Overexpression of REST in
primary cortical neurons alleviated PrP106-126 peptide-induced neuronal oxidative
stress, mitochondrial damage and partly inhibition of the LRP6-Wnt-beta-catenin
and Akt-mTOR signaling. Based on our findings, a model of REST-mediated
neuroprotection in prion infected animals is proposed, with Akt-mTOR and Wnt-beta
catenin signaling as the key pathways. REST-mediated neuronal survival signaling
could be explored as a viable therapeutic target for prion diseases and related
neurodegenerative diseases.
PMID- 28515682
TI - Nitric Oxide Synthase Inhibitor Attenuates the Effects of Repeated Restraint
Stress on Synaptic Transmission in the Paraventricular Nucleus of the Rat
Hypothalamus.
AB - Corticotropin-releasing hormone (CRH)-synthesizing parvocellular neuroendocrine
cells (PNCs) of the hypothalamic paraventricular nucleus (PVN) play a key role in
the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis. Several
studies have demonstrated that synaptic inputs to these cells may undergo stress
related enhancement but, on the other hand, it has been reported that exposition
to the same stressor for prolonged time periods may induce a progressive
reduction in the response of the HPA axis to homotypic stressors. In the present
study rats were subjected to 10 min restraint sessions, repeated twice daily for
3 or 7 days. Miniature excitatory and inhibitory postsynaptic currents (mEPSCs
and mIPSCs) were then recorded from PNCs in ex vivo hypothalamic slice
preparations obtained 24 h after the last restraint. Restraint stress repeated
over 3 days resulted in increased mean frequency and decreased rise time and
decay time constant of mEPSCs, accompanied by a decrease in the excitability of
PNCs, however, no such changes were evident in slices obtained from rats
subjected to restraint over 7 days. There were no changes in mIPSCs after
repeated restraint. Administration of the unspecific nitric oxide synthase (NOS)
blocker Nomega-Nitro-L-arginine (L-NNA) before each restraint, repeated over 3
days, prevented the occurrence of an increase in mEPSC frequency. However,
animals receiving L-NNA and subjected to repeated restraint had similar changes
in PNCs membrane excitability and mEPSC kinetics as stressed rats not receiving L
NNA. Comparison of the effects of a single 10 min restraint session followed by
either an immediate or delayed (24 h) decapitation revealed an increase in the
mean mEPSC frequency and a decrease in the mean mIPSC frequency in slices
prepared immediately after restraint, with no apparent effects when slice
preparation was delayed by 24 h. These results demonstrate that restraint,
lasting 10 min and repeated twice daily for 3 days, induces a selective and long
lasting enhancement of excitatory synaptic input onto PNCs, partially by a NOS
dependent mechanism, and reduces PNC excitability, whereas prolongation of
repeated stress for up to 7 days results in an adaptation.
PMID- 28515681
TI - The Activity-Induced Long Non-Coding RNA Meg3 Modulates AMPA Receptor Surface
Expression in Primary Cortical Neurons.
AB - Transcription of new RNA is crucial for maintaining synaptic plasticity, learning
and memory. Although the importance of synaptic plasticity-related messenger RNAs
(mRNAs) is well established, the role of a large group of long non-coding RNAs
(lncRNAs) in long-term potentiation (LTP) is not known. In this study, we
demonstrated the expression of a lncRNA cluster, namely maternally expressed gene
3 (Meg3), retrotransposon-like gene 1-anti-sense (Rtl1-AS), Meg8 and Meg9, which
is located in the maternally imprinted Dlk1-Dio3 region on mouse chromosome
12qF1, in primary cortical neurons following glycine stimulation in an N-Methyl-D
aspartate receptor (NMDAR)-dependent manner. Importantly, we also validated the
expression of Meg3, Meg8 and Meg9 in the hippocampus of mice following cued fear
conditioning in vivo. Interestingly, Meg3 is the only lncRNA that is expressed in
the nucleus and cytoplasm. Further analysis revealed that Meg3 loss of function
blocked the glycine-induced increase of the GluA1 subunit of AMPA receptors on
the plasma membrane, a major hallmark of LTP. This aberrant trafficking of AMPA
receptors correlated with the dysregulation of the phosphatidylinoside-3-kinase
(PI3K)/AKT signaling pathway and the downregulation of the lipid phosphatase and
tensin homolog (PTEN). These findings provide the first evidence for a functional
role of the lncRNA Meg3 in the intricate regulation of the PTEN/PI3K/AKT
signaling cascade during synaptic plasticity in neurons.
PMID- 28515680
TI - Trk Receptors and Neurotrophin Cross-Interactions: New Perspectives Toward
Manipulating Therapeutic Side-Effects.
AB - Some therapeutic side-effects result from simultaneous activation of homolog
receptors by the same ligand. Tropomyosin receptor kinases (TrkA, TrkB and TrkC)
play a major role in the development and biology of neurons through neurotrophin
signaling. The wide range of cross-interactions between Trk receptors and
neurotrophins vary in selectivity, affinity and function. In this study, we
discuss new perspectives to the manipulation of side-effects via a better
understanding of the cross-interactions at the molecular level, derived by
computational methods. Available crystal structures of Trk receptors and
neurotrophins are a valuable resource for exploitation via molecular mechanics
(MM) and dynamics (MD). The study of the energetics and dynamics of neurotrophins
or neurotrophic peptides interacting with Trk receptors will provide insight to
structural regions that may be candidates for drug targeting and signaling
pathway selection.
PMID- 28515674
TI - Perioperative management of patients on direct oral anticoagulants.
AB - Direct oral anticoagulants (DOACs) have been licensed worldwide for several years
for various indications. Each year, 10-15% of patients on oral anticoagulants
will undergo an invasive procedure and expert groups have issued several
guidelines on perioperative management in such situations. The perioperative
guidelines have undergone numerous updates as clinical experience of emergency
management has increased and perioperative studies including measurement of
residual anticoagulant levels have been published. The high inter-patient
variability of DOAC plasma levels has challenged the traditional recommendation
that perioperative DOAC interruption should be based only on the elimination half
life of DOACs, especially before invasive procedures carrying a high risk of
bleeding. Furthermore, recent publications have highlighted the potential danger
of heparin bridging use when DOACs are stopped before an invasive procedure. As
antidotes are progressively becoming available to manage severe bleeding or
urgent procedures in patients on DOACs, accurate laboratory tests have become the
standard to guide their administration and their actions need to be well
understood by clinicians. This review aims to provide a systematic approach to
managing patients on DOACs, based on recent updates of various perioperative
guidance, and highlighting the advantages and limits of recommendations based on
pharmacokinetic properties and laboratory tests.
PMID- 28515685
TI - Pupillary Response to Negative Emotional Stimuli Is Differentially Affected in
Meditation Practitioners.
AB - Clinically, meditative practices have become increasingly relevant, decreasing
anxiety in patients and increasing antibody production. However, few studies have
examined the physiological correlates, or effects of the incorporation of
meditative practices. Because pupillary reactivity is a marker for autonomic
changes and emotional processing, we hypothesized that the pupillary responses of
mindfulness meditation practitioners (MP) and subjects without such practices
(non-meditators (NM)) differ, reflecting different emotional processing. In a
group of 11 MP and 9 NM, we recorded the pupil diameter using video-oculography
while subjects explored images with emotional contents. Although both groups
showed a similar pupillary response for positive and neutral images, negative
images evoked a greater pupillary contraction and a weaker dilation in the MP
group. Also, this group had faster physiological recovery to baseline levels.
These results suggest that mindfulness meditation practices modulate the response
of the autonomic nervous system, reflected in the pupillary response to negative
images and faster physiological recovery to baseline levels, suggesting that
pupillometry could be used to assess the potential health benefits of these
practices in patients.
PMID- 28515683
TI - A Population of Projection Neurons that Inhibits the Lateral Horn but Excites the
Antennal Lobe through Chemical Synapses in Drosophila.
AB - In the insect olfactory system, odor information is transferred from the antennal
lobe (AL) to higher brain areas by projection neurons (PNs) in multiple AL tracts
(ALTs). In several species, one of the ALTs, the mediolateral ALT (mlALT),
contains some GABAergic PNs; in the Drosophila brain, the great majority of
ventral PNs (vPNs) are GABAergic and project through this tract to the lateral
horn (LH). Most excitatory PNs (ePNs), project through the medial ALT (mALT) to
the mushroom body (MB) and the LH. Recent studies have shown that GABAergic vPNs
play inhibitory roles at their axon terminals in the LH. However, little is known
about the properties and functions of vPNs at their dendritic branches in the AL.
Here, we used optogenetic and patch clamp techniques to investigate the
functional roles of vPNs in the AL. Surprisingly, our results show that specific
activation of vPNs reliably elicits strong excitatory postsynaptic potentials
(EPSPs) in ePNs. Moreover, the connections between vPNs and ePNs are mediated by
direct chemical synapses. Neither pulses of GABA, nor pharmagological, or genetic
blockade of GABAergic transmission gave results consistent with the involvement
of GABA in vPN-ePN excitatory transmission. These unexpected results suggest new
roles for the vPN population in olfactory information processing.
PMID- 28515686
TI - Innate and Cultural Spatial Time: A Developmental Perspective.
AB - We reviewed literature to understand when a spatial map for time is available in
the brain. We carefully defined the concepts of metrical map of time and of
conceptual representation of time as the mental time line (MTL) in order to
formulate our position. It is that both metrical map and conceptual
representation of time are spatial in nature. The former should be innate,
related to motor/implicit timing, it should represent all magnitudes with an
analogic and bi-dimensional structure. The latter MTL should be learned,
available at about 8-10 years-old and related to cognitive/explicit time. It
should have uni-dimensional, linear and directional structure (left-to-right in
Western culture). We bear the centrality of the development of number cognition,
of time semantic concepts and of reading/writing habits for the development of
ordinality and linearity of the MTL.
PMID- 28515684
TI - Selegiline Ameliorates Depression-Like Behavior in Mice Lacking the CD157/BST1
Gene, a Risk Factor for Parkinson's Disease.
AB - Parkinson's disease (PD), a neurodegenerative disorder, is accompanied by various
non-motor symptoms including depression and anxiety, which may precede the onset
of motor symptoms. Selegiline is an irreversible monoamine oxidase-B (MAO-B)
inhibitor, and is widely used in the treatment of PD and major depression.
However, there are few reports about the effects of selegiline on non-motor
symptoms in PD. The aim of this study was to explore the antidepressant and
anxiolytic effects of selegiline, using CD157/BST1 knockout (CD157 KO) mouse, a
PD-related genetic model displaying depression and anxiety, compared with other
antiparkinsonian drugs and an antidepressant, and was to investigate the effects
of selegiline on biochemical parameters in emotion-related brain regions. A
single administration of selegiline (1-10 mg/kg) dose-dependently reduced
immobility time in the forced swimming test (FST) in CD157 KO mice, but not
C57BL/6N wild-type (WT) mice. At 10 mg/kg, but not 3 mg/kg, selegiline
significantly increased climbing time in CD157 KO mice. A single administration
of the antiparkinsonian drugs pramipexole (a dopamine (DA) D2/D3 receptor
agonist) or rasagiline (another MAO-B inhibitor), and repeated injections of a
noradrenergic and specific serotonergic antidepressant (NaSSA), mirtazapine, also
decreased immobility time, but did not increase climbing time, in CD157 KO mice.
The antidepressant-like effects of 10 mg/kg selegiline were comparable to those
of 10 mg/kg rasagiline, and tended to be stronger than those of 1 mg/kg
rasagiline. After the FST, CD157 KO mice showed decreases in striatal and
hippocampal serotonin (5-HT) content, cortical norepinephrine (NE) content, and
plasma corticosterone concentration. A single administration of selegiline at 10
mg/kg returned striatal 5-HT, cortical NE, and plasma corticosterone levels to
those observed in WT mice. In the open field test (OFT), repeated administration
of mirtazapine had anxiolytic effects, and selegiline nonsignificantly
ameliorated anxiety-like behaviors in CD157 KO mice. In the social interaction
and preference tests, repeated mirtazapine ameliorated the high anxiety and low
sociability of CD157 KO mice, whereas selegiline did not. These results indicate
that selegiline has antidepressant and mild anxiolytic effects in CD157 KO mice,
and suggest that it is an effective antiparkinsonian drug for depressive and
anxiety symptoms in PD patients with a CD157 single nucleotide polymorphism
(SNP).
PMID- 28515687
TI - Effects of Passive Finger Movement on Cortical Excitability.
AB - This study examined the effects of joint angle and passive movement direction on
corticospinal excitability. The subjects were 14 healthy adults from whom consent
could be obtained. We performed two experiments. In Experiment 1, we measured
motor evoked potential (MEP) amplitude, F-wave and M-wave at 0 degrees and 20
degrees adduction during adduction or abduction movement, in the range of
movement from 10 degrees abduction to 30 degrees adduction. In Experiment 2,
MEPs were measured at static 0 degrees and 20 degrees adduction during passive
adduction from 10 degrees adduction to 30 degrees adduction and static 20
degrees adduction. MEP, F-waves and M-waves were recorded from the right first
dorsal interosseous (FDI) muscle. Experiment 1 revealed significantly increased
MEP amplitude at 0 degrees during passive adduction compared to static 0 degrees
(p < 0.01). No other significant differences in MEP, M-wave and F-wave
parameters were observed. In Experiment 2, MEP amplitude was significantly higher
at 20 degrees adduction during passive adduction compared with static 0 degrees
(p < 0.01). Based on these findings, it appears that fluctuations in MEP
amplitude values during passive movement are not influenced by joint angle, but
rather it is possible that it is due to intracortical afferent facilitation (AF)
dependent on afferent input due to the start of movement and interstimulus
interval (ISI) of transcranial magnetic stimulation (TMS).
PMID- 28515689
TI - Current Experimental Studies of Gene Therapy in Parkinson's Disease.
AB - Parkinson's disease (PD) was characterized by late-onset, progressive dopamine
neuron loss and movement disorders. The progresses of PD affected the neural
function and integrity. To date, most researches had largely addressed the
dopamine replacement therapies, but the appearance of L-dopa-induced dyskinesia
hampered the use of the drug. And the mechanism of PD is so complicated that it's
hard to solve the problem by just add drugs. Researchers began to focus on the
genetic underpinnings of Parkinson's disease, searching for new method that may
affect the neurodegeneration processes in it. In this paper, we reviewed current
delivery methods used in gene therapies for PD, we also summarized the primary
target of the gene therapy in the treatment of PD, such like neurotrophic factor
(for regeneration), the synthesis of neurotransmitter (for prolong the duration
of L-dopa), and the potential proteins that might be a target to modulate via
gene therapy. Finally, we discussed RNA interference therapies used in
Parkinson's disease, it might act as a new class of drug. We mainly focus on the
efficiency and tooling features of different gene therapies in the treatment of
PD.
PMID- 28515691
TI - Corrigendum: Identification of Cerebral Metal Ion Imbalance in the Brain of
Ageing Octodon degus.
AB - [This corrects the article on p. 66 in vol. 9, PMID: 28405187.].
PMID- 28515692
TI - Wu-Tou Decoction in Rheumatoid Arthritis: Integrating Network Pharmacology and In
Vivo Pharmacological Evaluation.
AB - Purpose: This study aimed to explore underlying action mechanism of Wu-Tou
decoction (WTD) in rheumatoid arthritis (RA) through network pharmacology
prediction and experimental verification. Methods: Chemical compounds and human
target proteins of WTD as well as RA-related human genes were obtained from TCM
Database @ Taiwan, PubChem and GenBank, respectively. Subsequently, molecular
networks and canonical pathways presumably involved in the treatment of WTD on RA
were generated by ingenuity pathway analysis (IPA) software. Furthermore,
experimental validation was carried out with MIP-1beta-induced U937 cell model
and collagen induced arthritis (CIA) rat model. Results: CCR5 signaling pathway
in macrophages was shown to be the top one shared signaling pathway associated
with both cell immune response and cytokine signaling. In addition, protein
kinase C (PKC) delta and p38 in this pathway were treated as target proteins of
WTD in RA. In vitro experiments indicated that WTD inhibited MIP-1beta-induced
production of TNF-alpha, MIP-1alpha, and RANTES as well as phosphorylation of
CCR5, PKC delta, and p38 in U937 cells. WTD treatment maintained the inhibitory
effects on production of TNF-alpha and RANTES in MIP-1beta-induced U937 cells
after CCR5 knockdown. In vivo experiments demonstrated that WTD ameliorated
symptoms in CIA rats, decreased the levels of IL-1beta, IL-2, IL-6, TNF-alpha,
MIP-1alpha, MIP-2, RANTES, and IP-10 in serum of CIA rats, as well as mRNA levels
of MIP-1alpha, MIP-2, RANTES, and IP-10 in ankle joints of CIA rats. Furthermore,
WTD also lowered the phosphorylation levels of CCR5, PKC delta and p38 in both
ankle joints and macrophages in ankle joints from CIA rats. Conclusion: It was
demonstrated in this research that WTD played a role in inhibiting inflammatory
response in RA which was closely connected with the modulation effect of WTD on
CCR5 signaling pathway in macrophages.
PMID- 28515688
TI - Insulin Resistance as a Link between Amyloid-Beta and Tau Pathologies in
Alzheimer's Disease.
AB - Current hypotheses and theories regarding the pathogenesis of Alzheimer's disease
(AD) heavily implicate brain insulin resistance (IR) as a key factor. Despite the
many well-validated metrics for systemic IR, the absence of biomarkers for brain
specific IR represents a translational gap that has hindered its study in living
humans. In our lab, we have been working to develop biomarkers that reflect the
common mechanisms of brain IR and AD that may be used to follow their engagement
by experimental treatments. We present two promising biomarkers for brain IR in
AD: insulin cascade mediators probed in extracellular vesicles (EVs) enriched for
neuronal origin, and two-dimensional magnetic resonance spectroscopy (MRS)
measures of brain glucose. As further evidence for a fundamental link between
brain IR and AD, we provide a novel analysis demonstrating the close spatial
correlation between brain expression of genes implicated in IR (using Allen Human
Brain Atlas data) and tau and beta-amyloid pathologies. We proceed to propose the
bold hypotheses that baseline differences in the metabolic reliance on
glycolysis, and the expression of glucose transporters (GLUT) and insulin
signaling genes determine the vulnerability of different brain regions to Tau
and/or Amyloid beta (Abeta) pathology, and that IR is a critical link between
these two pathologies that define AD. Lastly, we provide an overview of ongoing
clinical trials that target IR as an angle to treat AD, and suggest how
biomarkers may be used to evaluate treatment efficacy and target engagement.
PMID- 28515693
TI - Rolipram Improves Outcome in a Rat Model of Infant Sepsis-Induced Cardiorenal
Syndrome.
AB - While the mortality rate associated with sepsis in children has fallen over the
years, it still remains unacceptably high. The development of both acute cardiac
dysfunction and acute kidney injury during severe sepsis is categorized as type 5
cardiorenal syndrome (CRS) and is poorly understood in infants. To address this
lack of understanding and the need for an appropriate animal model in which to
conduct relevant preclinical studies, we developed a model of infant sepsis
induced CRS in rat pups then evaluated the therapeutic potential of the
phosphodiesterase (PDE) 4 inhibitor, rolipram. Rat pups at 17-18-days old were
subjected to cecal ligation and puncture (CLP) to induce fecal polymicrobial
sepsis. Uptake of Evans Blue dye was used to assess renal microvascular leakage.
Intravital videomicroscopy was used to assess renal microvascular perfusion and
oxidant generation. Glomerular filtration rate (GFR) was used to assess renal
function. Left ventricular (LV) catheterization and echocardiography were used to
assess cardiac function. Impairment of both cardiac and renal function developed
rapidly following CLP, indicating type 5 CRS. Most notable were the rapid decline
in LV diastolic function, the decline in cardiac output, renal microvascular
failure, and the decline in GFR. A dose-response study with rolipram determined
0.1 mg/kg, ip as the lowest most efficacious dose to protect the renal
microcirculation. Rolipram was then evaluated using a clinically relevant delayed
dosing paradigm (a single dose at 6 h post-CLP). With delayed dosing, rolipram
restored the renal microcirculation and reduced microvascular leakage but did not
reduce oxidant generation in the kidney nor restore GFR. In contrast, delayed
dosing with rolipram restored cardiac function. Rolipram also improved 4-days
survival. In summary, CLP in the rat pup produces a clinically relevant pediatric
model of sepsis-induced CRS. The PDE4 inhibitor rolipram was effective in
improving renal microvascular function and cardiac function, which improved
mortality. These findings suggest that rolipram should be evaluated further as
adjunctive therapy for the septic infant with CRS.
PMID- 28515694
TI - FAM20A Gene Mutation: Amelogenesis or Ectopic Mineralization?
AB - Background and objective:FAM20A gene mutations result in enamel renal syndrome
(ERS) associated with amelogenesis imperfecta (AI), nephrocalcinosis, gingival
fibromatosis, and impaired tooth eruption. FAM20A would control the
phosphorylation of enamel peptides and thus enamel mineralization. Here, we
characterized the structure and chemical composition of unerupted tooth enamel
from ERS patients and healthy subjects. Methods: Tooth sections were analyzed by
Scanning Electron Microscopy (SEM), Energy Dispersive Spectroscopy (EDS), X-Ray
Diffraction (XRD), and X-Ray Fluorescence (XRF). Results: SEM revealed that
prisms were restricted to the inner-most enamel zones. The bulk of the
mineralized matter covering the crown was formed by layers with varying electron
densities organized into lamellae and micronodules. Tissue porosity progressively
increased at the periphery, ending with loose and unfused nanonodules also
observed in the adjoining soft tissues. Thus, the enamel layer covering the
dentin in all ERS patients (except a limited layer of enamel at the dentino
enamel junction) displayed an ultrastructural globular pattern similar to one
observed in ectopic mineralization of soft tissue, notably in the gingiva of
Fam20a knockout mice. XRD analysis confirmed the existence of alterations in
crystallinity and composition (vs. sound enamel). XRF identified lower levels of
calcium and phosphorus in ERS enamel. Finally, EDS confirmed the reduced amount
of calcium in ERS enamel, which appeared similar to dentin. Conclusion: This
study suggests that, after an initial normal start to amelogenesis, the bulk of
the tissue covering coronal dentin would be formed by different mechanisms based
on nano- to micro-nodule aggregation. This evocated ectopic mineralization
process is known to intervene in several soft tissues in FAM20A gene mutant.
PMID- 28515700
TI - The Measurement of Aesthetic Emotion in Music.
PMID- 28515698
TI - How Will the Mild Encephalitis Hypothesis of Schizophrenia Influence
Stigmatization?
PMID- 28515699
TI - Active Involvement of End Users When Developing Web-Based Mental Health
Interventions.
AB - BACKGROUND: Although many web-based mental health interventions are being
released, the actual uptake by end users is limited. The marginal level of
engagement of end users when developing these interventions is recognized as an
important cause for uptake problems. In this paper, we offer our perceptive on
how to improve user engagement. By doing so, we aim to stimulate a discourse on
user involvement within the field of online mental health interventions. METHODS:
We shortly describe three different methods (the expert-driven method,
intervention mapping, and scrum) that were currently used to develop web-based
health interventions. We will focus to what extent the end user was involved in
the developmental phase, and what the additional challenges were. In the final
paragraph, lessons learned are summarized, and recommendations provided. RESULTS:
Every method seems to have its trade-off: if end users are highly involved,
availability of end users and means become problematic. If end users are less
actively involved, the product may be less appropriate for the end user. Other
challenges to consider are the funding of the more active role of technological
companies, and the time it takes to process the results of shorter development
cycles. CONCLUSION: Thinking about user-centered design and carefully planning,
the involvement of end users should become standard in the field of web-based
(mental) health. When deciding on the level of user involvement, one should
balance the need for input from users with the availability of resources such as
time and funding.
PMID- 28515701
TI - Commentary: From 'sense of number' to 'sense of magnitude' - The role of
continuous magnitudes in numerical cognition.
PMID- 28515702
TI - On the Tacit Aspects of Science Pedagogy in Higher Education.
AB - In this article, we examine the concept of tacit knowledge and its implications
for science education. We suggest that the history of scientific ideas and the
personal nature of learning imply that higher education in scientific fields,
wherein the generation of new knowledge, insights and understanding is paramount,
would greatly benefit by acknowledging the irreducible role of the non-formal and
the incidental in scientific innovation and advances.
PMID- 28515697
TI - TRPA1 Channels Modify TRPV1-Mediated Current Responses in Dorsal Root Ganglion
Neurons.
AB - The transient receptor potential vanilloid 1 (TRPV1) channel is highly expressed
in a subset of sensory neurons in the dorsal root ganglia (DRG) and trigeminal
ganglia of experimental animals, responsible for nociception. Many researches
have revealed that some TRPV1-positive neurons co-express the transient receptor
potential ankyrin 1 (TRPA1) channel whose activities are closely modulated by
TRPV1 channel. However, it is less investigated whether the activities of TRPV1
channel are modulated by the presence of TRPA1 channel in primary sensory
neurons. This study clarified the difference in electrophysiological responses
induced by TRPV1 channel activation between TRPA1-positive and TRPA1-negative
DRG. TRPV1 and TRPA1 channel activations were evoked by capsaicin (1 MUM), a
TRPV1 agonist, and allyl isothiocyanate (AITC; 500 MUM), a TRPA1 agonist,
respectively. Capsaicin perfusion for 15 s caused a large inward current without
a desensitization phase at a membrane potential of -70 mV in AITC-insensitive DRG
(current density; 29.6 +/- 5.6 pA/pF, time constant of decay; 12.8 +/- 1.8 s).
The capsaicin-induced currents in AITC-sensitive DRG had a small current density
(12.7 +/- 2.9 pA/pF) with a large time constant of decay (24.3 +/- 5.4 s). In
calcium imaging with Fura-2, the peak response by capsaicin was small and
duration reaching the peak response was long in AITC-sensitive neurons. These
electrophysiological differences were completely eliminated by HC-030031, a TRPA1
antagonist, in an extracellular solution or 10 mM EGTA, a Ca2+ chelator, in an
internal solution. Capsaicin perfusion for 120 s desensitized the inward currents
after a transient peak. The decay during capsaicin perfusion was notably slow in
AITC-sensitive DRG; ratio of capsaicin-induced current 60 s after the treatment
per the peak current in AITC-sensitive neurons (78 +/- 9%) was larger than that
in AITC-insensitive neurons (48 +/- 5%). The capsaicin-induced current in the
desensitization phase was attenuated by HC-030031 in AITC-insensitive DRG. These
results indicate that (1) TRPV1-mediated currents in TRPA1-positive neurons
characterize small current densities with slow decay, which is caused by TRPA1
channel activities and intracellular Ca2+ mobilization and (2) desensitization of
TRPV1-mediated current in TRPA1-positive neurons is apparently slow, due to
appending TRPA1-mediated current.
PMID- 28515695
TI - Chronic Endurance Exercise Impairs Cardiac Structure and Function in Middle-Aged
Mice with Impaired Nrf2 Signaling.
AB - Nuclear factor erythroid 2 related factor 2 (Nrf2) signaling maintains the redox
homeostasis and its activation is shown to suppress cardiac maladaptation.
Earlier we reported that acute endurance exercise (2 days) evoked antioxidant
cytoprotection in young WT animals but not in aged WT animals. However, the
effect of repeated endurance exercise during biologic aging (WT) characterized by
an inherent deterioration in Nrf2 signaling and pathological aging (pronounced
oxidative susceptibility-Nrf2 absence) in the myocardium remains elusive. Thus,
the purpose of our study was to determine the effect of chronic endurance
exercise-induced cardiac adaptation in aged mice with and without Nrf2. Age
matched WT and Nrf2-null mice (Nrf2-/-) (>22 months) were subjected to 6 weeks
chronic endurance exercise (25 meter/min, 12% grade). The myocardial redox status
was assessed by expression of antioxidant defense genes and proteins along with
immunochemical detection of DMPO-radical adduct, GSH-NEM, and total
ubiquitination. Cardiac functions were assessed by echocardiography and
electrocardiogram. At sedentary state, loss of Nrf2 resulted in significant
downregulation of antioxidant gene expression (Nqo1, Ho1, Gclm, Cat, and Gst
alpha) with decreased GSH-NEM immuno-fluorescence signals. While Nrf2-/- mice
subjected to CEE showed an either similar or more pronounced reduction in the
transcript levels of Gclc, Nqo1, Gsr, and Gst-alpha in relation to WT
littermates. In addition, the hearts of Nrf2-/- on CEE showed a substantial
reduction in specific antioxidant proteins, G6PD and CAT along with decreased
GSH, a pronounced increase in DMPO-adduct and the total ubiquitination levels.
Further, CEE resulted in a significant upregulation of hypertrophy genes (Anf,
Bnf, and beta-Mhc) (p < 0.05) in the Nrf2-/- hearts in relation to WT mice.
Moreover, the aged Nrf2-/- mice exhibited a higher degree of cardiac remodeling
in association with a significant decrease in fractional shortening, pronounced
ST segment, and J wave elevation upon CEE compared to age-matched WT littermates.
In conclusion, our findings indicate that while the aged WT and Nrf2 knockout
animals both exhibit hypertrophy after CEE, the older Nrf2 knockouts showed
ventricular remodeling coupled with profound cardiac functional abnormalities and
diastolic dysfunction.
PMID- 28515696
TI - The Reliability and Validity of a Four-Minute Running Time-Trial in Assessing
[Formula: see text]max and Performance.
AB - Introduction: Traditional graded-exercise tests to volitional exhaustion (GXTs)
are limited by the need to establish starting workloads, stage durations, and
step increments. Short-duration time-trials (TTs) may be easier to implement and
more ecologically valid in terms of real-world athletic events. The purpose of
the current study was to assess the reliability and validity of maximal oxygen
uptake ([Formula: see text]max) and performance measured during a traditional GXT
(STEP) and a four-minute running time-trial (RunTT). Methods: Ten recreational
runners (age: 32 +/- 7 years; body mass: 69 +/- 10 kg) completed five STEP tests
with a verification phase (VER) and five self-paced RunTTs on a treadmill. The
order of the STEP/VER and RunTT trials was alternated and counter-balanced.
Performance was measured as time to exhaustion (TTE) for STEP and VER and
distance covered for RunTT. Results: The coefficient of variation (CV) for
[Formula: see text]max was similar between STEP, VER, and RunTT (1.9 +/- 1.0, 2.2
+/- 1.1, and 1.8 +/- 0.8%, respectively), but varied for performance between the
three types of test (4.5 +/- 1.9, 9.7 +/- 3.5, and 1.8 +/- 0.7% for STEP, VER,
and RunTT, respectively). Bland-Altman limits of agreement (bias +/- 95%) showed
[Formula: see text]max to be 1.6 +/- 3.6 mL.kg-1.min-1 higher for STEP vs. RunTT.
Peak HR was also significantly higher during STEP compared with RunTT (P =
0.019). Conclusion: A four-minute running time-trial appears to provide more
reliable performance data in comparison to an incremental test to exhaustion, but
may underestimate [Formula: see text]max.
PMID- 28515690
TI - Brain Renin-Angiotensin System and Microglial Polarization: Implications for
Aging and Neurodegeneration.
AB - Microglia can transform into proinflammatory/classically activated (M1) or anti
inflammatory/alternatively activated (M2) phenotypes following environmental
signals related to physiological conditions or brain lesions. An adequate
transition from the M1 (proinflammatory) to M2 (immunoregulatory) phenotype is
necessary to counteract brain damage. Several factors involved in microglial
polarization have already been identified. However, the effects of the brain
renin-angiotensin system (RAS) on microglial polarization are less known. It is
well known that there is a "classical" circulating RAS; however, a second RAS
(local or tissue RAS) has been observed in many tissues, including brain. The
locally formed angiotensin is involved in local pathological changes of these
tissues and modulates immune cells, which are equipped with all the components of
the RAS. There are also recent data showing that brain RAS plays a major role in
microglial polarization. Level of microglial NADPH-oxidase (Nox) activation is a
major regulator of the shift between M1/proinflammatory and M2/immunoregulatory
microglial phenotypes so that Nox activation promotes the proinflammatory and
inhibits the immunoregulatory phenotype. Angiotensin II (Ang II), via its type 1
receptor (AT1), is a major activator of the NADPH-oxidase complex, leading to pro
oxidative and pro-inflammatory effects. However, these effects are counteracted
by a RAS opposite arm constituted by Angiotensin II/AT2 receptor signaling and
Angiotensin 1-7/Mas receptor (MasR) signaling. In addition, activation of
prorenin-renin receptors may contribute to activation of the proinflammatory
phenotype. Aged brains showed upregulation of AT1 and downregulation of AT2
receptor expression, which may contribute to a pro-oxidative pro-inflammatory
state and the increase in neuron vulnerability. Several recent studies have shown
interactions between the brain RAS and different factors involved in microglial
polarization, such as estrogens, Rho kinase (ROCK), insulin-like growth factor-1
(IGF-1), tumor necrosis factor alpha (TNF)-alpha, iron, peroxisome proliferator
activated receptor gamma, and toll-like receptors (TLRs). Metabolic reprogramming
has recently been involved in the regulation of the neuroinflammatory response.
Interestingly, we have recently observed a mitochondrial RAS, which is altered in
aged brains. In conclusion, dysregulation of brain RAS plays a major role in
aging-related changes and neurodegeneration by exacerbation of oxidative stress
(OS) and neuroinflammation, which may be attenuated by pharmacological
manipulation of RAS components.
PMID- 28515703
TI - Managing Contextual Complexity in an Experiential Learning Course: A Dynamic
Systems Approach through the Identification of Turning Points in Students'
Emotional Trajectories.
AB - This study adopts a dynamic systems approach to investigate how individuals
successfully manage contextual complexity. To that end, we tracked individuals'
emotional trajectories during a challenging training course, seeking qualitative
changes-turning points-and we tested their relationship with the perceived
complexity of the training. The research context was a 5-day higher education
course based on process-oriented experiential learning, and the sample consisted
of 17 students. The students used a five-point Likert scale to rate the intensity
of 16 emotions and the complexity of the training on 8 measurement points. Monte
Carlo permutation tests enabled to identify 30 turning points in the 272
emotional trajectories analyzed (17 students * 16 emotions each). 83% of the
turning points indicated a change of pattern in the emotional trajectories that
consisted of: (a) increasingly intense positive emotions or (b) decreasingly
intense negative emotions. These turning points also coincided with particularly
complex periods in the training as perceived by the participants (p = 0.003, and
p = 0.001 respectively). The relationship between positively-trended turning
points in the students' emotional trajectories and the complexity of the training
may be interpreted as evidence of a successful management of the cognitive
conflict arising from the clash between the students' prior ways of meaning
making and the challenging demands of the training. One of the strengths of this
study is that it provides a relatively simple procedure for identifying turning
points in developmental trajectories, which can be applied to various
longitudinal experiences that are very common in educational and developmental
contexts. Additionally, the findings contribute to sustaining that the assumption
that complex contextual demands lead unfailingly to individuals' learning is
incomplete. Instead, it is how individuals manage complexity which may or may not
lead to learning. Finally, this study can also be considered a first step in
research on the developmental potential of process-oriented experiential learning
training.
PMID- 28515704
TI - Two Trackers Are Better than One: Information about the Co-actor's Actions and
Performance Scores Contribute to the Collective Benefit in a Joint Visuospatial
Task.
AB - When humans collaborate, they often distribute task demands in order to reach a
higher performance compared to performing the same task alone (i.e., a collective
benefit). Here, we tested to what extent receiving information about the actions
of a co-actor, performance scores, or receiving both types of information impacts
the collective benefit in a collaborative multiple object tracking task. In a
between-subject design, pairs of individuals jointly tracked a subset of target
objects among several moving distractor objects on a computer screen for a 100
trials. At the end of a trial, pairs received performance scores (Experiment 1),
information about their partner's target selections (Experiment 2), or both types
of information (Experiment 3). In all experiments, the performance of the pair
exceeded the individual performances and the simulated performance of two
independent individuals combined. Initially, when receiving both types of
information (Experiment 3), pairs achieved the highest performance and divided
task demands most efficiently compared to the other two experiments. Over time,
performances and the ability to divide task demands for pairs receiving a single
type of information converged with those receiving both, suggesting that pairs'
coordination strategies become equally effective over time across experiments.
However, pairs' performances never reached a theoretical limit of performance in
all experiments. For distributing task demands, members of a pair predominantly
used a left-right division of labor strategy (i.e., the leftmost targets were
tracked by one co-actor while the rightmost targets were tracked by the other co
actor). Overall, findings of the present study suggest that receiving information
about actions of a co-actor, performance scores, or receiving both enables pairs
to devise effective division of labor strategies in a collaborative visuospatial
task. However, when pairs had both types of information available, the formation
of division of labor strategies was facilitated, indicating that pairs benefited
the most from having both types of information available (i.e., actions about the
co-actor and performance scores). Findings are applicable to circumstances in
which humans need to perform collaborative visuospatial tasks that are time
critical and/or only allow a very limited exchange of information between co
actors.
PMID- 28515705
TI - Control and Effort Costs Influence the Motivational Consequences of Choice.
AB - The act of making a choice, apart from any outcomes the choice may yield, has,
paradoxically, been linked to both the enhancement and the detriment of intrinsic
motivation. Research has implicated two factors in potentially mediating these
contradictory effects: the personal control conferred by a choice and the costs
associated with a choice. Across four experiments, utilizing a physical effort
task disguised as a simple video game, we systematically varied costs across two
levels of physical effort requirements (Low-Requirement, High-Requirement) and
control over effort costs across three levels of choice (Free-Choice, Restricted
Choice, and No-Choice) to disambiguate how these factors affect the motivational
consequences of choosing within an effortful task. Together, our results
indicated that, in the face of effort requirements, illusory control alone may
not sufficiently enhance perceptions of personal control to boost intrinsic
motivation; rather, the experience of actual control may be necessary to overcome
effort costs and elevate performance. Additionally, we demonstrated that
conditions of illusory control, while otherwise unmotivating, can through
association with the experience of free-choice, be transformed to have a positive
effect on motivation.
PMID- 28515707
TI - Validation of Repeated Endothelial Function Measurements Using EndoPAT in Stroke.
AB - BACKGROUND: Decreased endothelial function (EF) may be a prognostic marker for
stroke. Measuring pharmacological effects on EF may be of interest in the
development of personalized medicine for stroke prevention. In this study, we
assessed the reliability of repeated EF measurements using a pulse amplitude
tonometry technology in acute stroke patients. Similarly, reliability was tested
in healthy subjects devoid of vascular disease to estimate reactivity and
reliability in a younger non-stroke population. MATERIALS AND METHODS: EF was
assessed using the EndoPAT2000 in 20 healthy volunteers (men 50%, mean age 35.85
+/- 3.47 years) and 21 stroke patients (men 52%, mean age 66.38 +/- 2.85 years,
and mean NIHSS 4.09 +/- 0.53) under standardized conditions. EF was measured as
the reactive hyperemia index (RHI), logarithm of RHI (lnRHI), and Framingham RHI
(fRHI). Measurements were separated by 1.5 and 24 h to assess same-day and day-to
day reliability, respectively. RESULTS: Fair to moderate correlations of
measurements [intraclass correlation coefficient (ICC)same-day 0.29 and ICCday-to
day 0.52] were detected in healthy subjects. In stroke patients, we found
moderate to substantial correlation of both same-day and day-to-day repeated
measurements (ICCsame-day 0.40 and ICCday-to-day 0.62). fRHI compared with RHI
and lnRHI showed best reliability. CONCLUSION: Repeated measurements of fRHI in
stroke patients show moderate reliability on same-day and substantial on day-to
day measurements. Likewise, in healthy subjects there was substantial reliability
on day-to-day measurement, but only moderate on same-day measurements. In
general, day-to-day correlation of repeated EF measurements was far better than
that of same-day measurements, which ranged from poor to moderate depending on
the specific outcome measure of EF. A possible carryover effect should be
considered if same-day repeated testing of drug effects is applied in future
studies.
PMID- 28515708
TI - Disrupted Structural and Functional Networks and Their Correlation with Alertness
in Right Temporal Lobe Epilepsy: A Graph Theory Study.
AB - Previous studies have shown that temporal lobe epilepsy (TLE) involves abnormal
structural or functional connectivity in specific brain areas. However, limited
comprehensive studies have been conducted on TLE associated changes in the
topological organization of structural and functional networks. Additionally,
epilepsy is associated with impairment in alertness, a fundamental component of
attention. In this study, structural networks were constructed using diffusion
tensor imaging tractography, and functional networks were obtained from resting
state functional MRI temporal series correlations in 20 right temporal lobe
epilepsy (rTLE) patients and 19 healthy controls. Global network properties were
computed by graph theoretical analysis, and correlations were assessed between
global network properties and alertness. The results from these analyses showed
that rTLE patients exhibit abnormal small-world attributes in structural and
functional networks. Structural networks shifted toward more regular attributes,
but functional networks trended toward more random attributes. After controlling
for the influence of the disease duration, negative correlations were found
between alertness, small-worldness, and the cluster coefficient. However,
alertness did not correlate with either the characteristic path length or global
efficiency in rTLE patients. Our findings show that disruptions of the
topological construction of brain structural and functional networks as well as
small-world property bias are associated with deficits in alertness in rTLE
patients. These data suggest that reorganization of brain networks develops as a
mechanism to compensate for altered structural and functional brain function
during disease progression.
PMID- 28515710
TI - Resistant Hypertension after Hypertensive Intracerebral Hemorrhage Is Associated
with More Medical Interventions and Longer Hospital Stays without Affecting
Outcome.
AB - BACKGROUND: Hypertension (HTN) is the most common cause of spontaneous
intracerebral hemorrhage (ICH). The aim of this study is to investigate the role
of resistant HTN in patients with ICH. METHODS AND RESULTS: We conducted a
retrospective study of all consecutive ICH admissions at our medical center from
November 2013 to October 2015. The clinical features of patients with resistant
HTN (requiring four or more antihypertensive agents to keep systolic blood
pressure <140 mm Hg) were compared with those with responsive HTN (requiring
three or fewer agents). Of the 152 patients with hypertensive ICH, 48 (31.6%) had
resistant HTN. Resistant HTN was independently associated with higher body mass
index and proteinuria. Compared to the responsive group, patients with resistant
HTN had higher initial blood pressures and greater requirement for ventilator
support, hematoma evacuation, hypertonic saline therapy, and nicardipine
infusion. Resistant HTN increases length of stay (LOS) in the intensive care unit
(ICU) (4.2 vs 2.1 days; p = 0.007) and in the hospital (11.5 vs 7.0 days; p =
0.003). Multivariate regression analysis showed that the rate of systolic blood
pressure >140 mm Hg and duration of nicardipine infusion were independently
associated with LOS in the ICU. There was no significant difference in hematoma
expansion and functional outcome at hospital discharge between the two groups.
CONCLUSION: Resistant HTN in patients with ICH is associated with more medical
interventions and longer LOS without effecting outcome at hospital discharge.
PMID- 28515709
TI - Effects of 10 Hz Repetitive Transcranial Magnetic Stimulation of the Left
Dorsolateral Prefrontal Cortex in Disorders of Consciousness.
AB - BACKGROUND: While repetitive transcranial magnetic stimulation (rTMS) has been
applied in treatment of patients with disorders of consciousness (DOC), a
standardized stimulation protocol has not been proposed, and its therapeutic
effects are inconsistently documented. OBJECTIVES: To assess the efficacy of rTMS
in improving consciousness in patients with persistent minimally conscious state
(MCS) or unresponsive wakefulness syndrome (UWS), previously known as vegetative
state (VS). METHOD: A prospective single-blinded study, with selected subjects,
was carried out. In total, 16 patients (5 MCS and 11 VS/UWS) with chronic DOC
were included. All patients received active 10 Hz rTMS at the left dorsolateral
prefrontal cortex (DLPFC), at one session per day, for 20 consecutive days. A
single daily session of stimulation consisted of 1,000 pulses (10 s of 10 Hz
trains; repeated 10 times with an inter-train interval of 60 s; and 11 min and 40
s for total session). The main outcome measures were changes in the total score
on the JFK Coma Recovery Scale-Revised (CRS-R) scale. Additional measures were
the impressions of caregivers after the conclusion of the interventions, which
were assessed using the Clinical Global Impression-Improvement (CGI-I) scale.
RESULTS: The CRS-R scores were increased in all 5 MCS patients and 4 of 11 VS/UWS
patients, while a significant enhancement of CRS-R scores was observed compared
to the baseline in all participants (p = 0.007). However, the improvement was
more notable in MCS patients (p = 0.042) than their VS/UWS counterparts (p =
0.066). Based on the CGI-I scores, two patients improved considerably, two
improved, six minimally improved, six experienced no change, and none
deteriorated. Good concordance was seen between the CGI-I result and the
increases in CRS-R scores. CONCLUSION: Treatment of 10 Hz multisession rTMS
applied to the left DLPFC is promising for the rehabilitation of DOC patients,
especially those in MCS. Further validation with a cohort of a larger sample size
is required.
PMID- 28515706
TI - Research Priorities in Limb and Task-Specific Dystonias.
AB - Dystonia, which causes intermittent or sustained abnormal postures and movements,
can present in a focal or a generalized manner. In the limbs, focal dystonia can
occur in either the upper or lower limbs and may be task-specific causing
abnormal motor performance for only a specific task, such as in writer's cramp,
runner's dystonia, or musician's dystonia. Focal limb dystonia can be non-task
specific and may, in some circumstances, be associated with parkinsonian
disorders. The true prevalence of focal limb dystonia is not known and is likely
currently underestimated, leaving a knowledge gap and an opportunity for future
research. The pathophysiology of focal limb dystonia shares some commonalities
with other dystonias with a loss of inhibition in the central nervous system and
a loss of the normal regulation of plasticity, called homeostatic plasticity.
Functional imaging studies revealed abnormalities in several anatomical networks
that involve the cortex, basal ganglia, and cerebellum. Further studies should
focus on distinguishing cause from effect in both physiology and imaging studies
to permit focus on most relevant biological correlates of dystonia. There is no
specific therapy for the treatment of limb dystonia given the variability in
presentation, but off-label botulinum toxin therapy is often applied to focal
limb and task-specific dystonia. Various rehabilitation techniques have been
applied and rehabilitation interventions may improve outcomes, but small sample
size and lack of direct comparisons between methods to evaluate comparative
efficacy limit conclusions. Finally, non-invasive and invasive therapeutic
modalities have been explored in small studies with design limitations that do
not yet clearly provide direction for larger clinical trials that could support
new clinical therapies. Given these gaps in our clinical, pathophysiologic, and
therapeutic knowledge, we have identified priorities for future research
including: the development of diagnostic criteria for limb dystonia, more precise
phenotypic characterization and innovative clinical trial design that considers
clinical heterogeneity, and limited available number of participants.
PMID- 28515711
TI - The Impact of Glucagon-Like Peptide-1 on Bone Metabolism and Its Possible
Mechanisms.
AB - The impact of antidiabetic drugs on bone metabolism is drawing increasing
attention due to the discovery of a correlation between type 2 diabetes mellitus
(T2DM) and osteoporosis. Glucagon-like peptide-1 (GLP-1) receptor agonists are a
novel and promising class of drugs for T2DM, which may also have clinical
applications in bone tissue disorders. This review examines the impact of GLP-1
on bone metabolism, including enhancement of bone mineral density and improvement
of bone quality. However, the precise effect of GLP-1 on fracture risk has not
been unambiguously defined. This review also summarizes our current understanding
of the mechanisms by which GLP-1 affects bone metabolism. GLP-1 may act on bone
by promoting bone formation, inhibiting bone resorption, and affecting the
coordination of the two processes. We describe molecular pathways and proteins,
such as Wnt and calcitonin, that are associated with GLP-1 and bone tissue. The
specific processes and related molecular mechanisms of the effects of GLP-1 on
bone metabolism need to be further explored and clarified.
PMID- 28515713
TI - Energy Efficiency and Productivity Enhancement of Microbial Electrosynthesis of
Acetate.
AB - It was hypothesized that a lack of acetogenic biomass (biocatalyst) at the
cathode of a microbial electrosynthesis system, due to electron and nutrient
limitations, has prevented further improvement in acetate productivity and
efficiency. In order to increase the biomass at the cathode and thereby
performance, a bioelectrochemical system with this acetogenic community was
operated under galvanostatic control and continuous media flow through a
reticulated vitreous carbon (RVC) foam cathode. The combination of galvanostatic
control and the high surface area cathode reduced the electron limitation and the
continuous flow overcame the nutrient limitation while avoiding the accumulation
of products and potential inhibitors. These conditions were set with the
intention of operating the biocathode through the production of H2. Biofilm
growth occurred on and within the unmodified RVC foam regardless of vigorous H2
generation on the cathode surface. A maximum volumetric rate or space time yield
for acetate production of 0.78 g/Lcatholyte/h was achieved with 8 A/Lcatholyte
(83.3 A/m2projected surface area of cathode) supplied to the continuous
flow/culture bioelectrochemical reactors. The total Coulombic efficiency in H2
and acetate ranged from approximately 80-100%, with a maximum of 35% in acetate.
The overall energy efficiency ranged from approximately 35-42% with a maximum to
acetate of 12%.
PMID- 28515712
TI - Allelic Variation in Outer Membrane Protein A and Its Influence on Attachment of
Escherichia coli to Corn Stover.
AB - Understanding the genetic factors that govern microbe-sediment interactions in
aquatic environments is important for water quality management and reduction of
waterborne disease outbreaks. Although chemical properties of bacteria have been
identified that contribute to initiation of attachment, the outer membrane
proteins that contribute to these chemical properties still remain unclear. In
this study we explored the attachment of 78 Escherichia coli environmental
isolates to corn stover, a representative agricultural residue. Outer membrane
proteome analysis led to the observation of amino acid variations, some of which
had not been previously described, in outer membrane protein A (OmpA) at 10
distinct locations, including each of the four extracellular loops, three of the
eight transmembrane segments, the proline-rich linker and the dimerization
domain. Some of the polymorphisms within loops 1, 2, and 3 were found to
significantly co-occur. Grouping of sequences according to the outer loop
polymorphisms revealed five distinct patterns that each occur in at least 5% of
our isolates. The two most common patterns, I and II, are encoded by 33.3 and
20.5% of these isolates and differ at each of the four loops. Statistically
significant differences in attachment to corn stover were observed among isolates
expressing different versions of OmpA and when different versions of OmpA were
expressed in the same genetic background. Most notable was the increased corn
stover attachment associated with a loop 3 sequence of SNFDGKN relative to the
standard SNVYGKN sequence. These results provide further insight into the allelic
variation of OmpA and implicate OmpA in contributing to attachment to corn
stover.
PMID- 28515715
TI - Anti-Biofilm and Antivirulence Activities of Metabolites from Plectosphaerella
cucumerina against Pseudomonas aeruginosa.
AB - This study reported the efficacy of the metabolites of Plectosphaerella
cucumerina, one phyllosphere fungus from Orychophragmus violaceus, against
Pseudomonas aeruginosa quorum sensing (QS) and QS-regulated biofilms. The minimum
inhibitory concentration (MIC) of the ethyl acetate (EtOAc) extract from P.
cucumerina against P. aeruginosa PAO1 was 1.25 mg mL-1. At sub-MIC
concentrations, P. cucumerina extract (0.25-1 mg mL-1) not only inhibited biofilm
formation but also disrupted preformed biofilms of P. aeruginosa PAO1 without
affecting its growth. Fluorescence and scanning electron microscope (SEM) showed
architectural disruption of the biofilms when treated with P. cucumerina
metabolites. Further investigation demonstrated that metabolites in P. cucumerina
attenuated the QS-dependent virulence factors. LC-MS/MS spectra coupled with
experimentally standard samples suggested that patulin and emodin might act as
the principal components possessing anti-biofilm and antivirulence activities.
This is the first report of (1) the isolation of P. cucumerina from the
phyllosphere of O. violaceus and (2) anti-biofilm, antivirulence, and biofilm
disruption activities of this fungus. Thus, this study provides fascinating new
pathways for screening antipathogenic agents.
PMID- 28515716
TI - Antifungal Activity of the Biphosphinic Cyclopalladate C7a against Candida
albicans Yeast Forms In Vitro and In Vivo.
AB - Vulvovaginal and invasive candidiasis are frequent conditions in immunosuppressed
individuals caused by Candida albicans and non-albicans Candida spp. Fluconazole
and Amphotericin B are the main drugs used to fight the infection. However,
resistance to fluconazole and other azole antifungal drugs is an important
clinical problem that encourages the search for new therapeutic alternatives. In
this work, we evaluate the antifungal activity of the biphosphinic cyclopalladate
C7a in the in vitro and in vivo model. Our results showed fungicidal activity,
with low values of minimal inhibitory concentrations and minimum fungicidal
concentrations, even for fluconazole and/or miconazole resistant Candida
isolates. Fluorescence microscopy and transmission electron microscopy revealed
that the compound was able to inhibit the formation of hyphae/pseudohyphae and,
moreover, promoted morphological alterations in cellular organelles and
structures, such as disruption of cell wall, apparent mitochondrial swelling,
chromatin marginalization into the nuclei and increased numbers of electron
lucent vacuoles. C7a significantly decreased the biofilm formation and reduced
the viability of yeast cells in mature biofilms when tested against a virulent C.
albicans strain. In vivo assays demonstrated a significant decrease of fungal
burden in local (vaginal canal) and disseminated (kidneys) infection. In
addition, we observed a significant increase in the survival of the systemically
infected animals treated with C7a. Our results suggest C7a as a novel therapeutic
agent for vaginal and disseminated candidiasis, and an alternative for
conventional drug-resistant Candida.
PMID- 28515718
TI - Fungal Diversity in Field Mold-Damaged Soybean Fruits and Pathogenicity
Identification Based on High-Throughput rDNA Sequencing.
AB - Continuous rain and an abnormally wet climate during harvest can easily lead to
soybean plants being damaged by field mold (FM), which can reduce seed yield and
quality. However, to date, the underlying pathogen and its resistance mechanism
have remained unclear. The objective of the present study was to investigate the
fungal diversity of various soybean varieties and to identify and confirm the FM
pathogenic fungi. A total of 62,382 fungal ITS1 sequences clustered into 164
operational taxonomic units (OTUs) with 97% sequence similarity; 69 taxa were
recovered from the samples by internal transcribed spacer (ITS) region
sequencing. The fungal community compositions differed among the tested soybeans,
with 42 OTUs being amplified from all varieties. The quadratic relationships
between fungal diversity and organ-specific mildew indexes were analyzed,
confirming that mildew on soybean pods can mitigate FM damage to the seeds. In
addition, four potentially pathogenic fungi were isolated from FM-damaged soybean
fruits; morphological and molecular identification confirmed these fungi as
Aspergillus flavus, A. niger, Fusarium moniliforme, and Penicillium chrysogenum.
Further re-inoculation experiments demonstrated that F. moniliforme is dominant
among these FM pathogenic fungi. These results lay the foundation for future
studies on mitigating or preventing FM damage to soybean.
PMID- 28515714
TI - New Insights into Pathogenic Vibrios Affecting Bivalves in Hatcheries: Present
and Future Prospects.
AB - Hatcheries constitute nowadays the only viable solution to support the husbandry
of bivalve molluscs due to the depletion and/or overexploitation of their natural
beds. Hatchery activities include the broodstock conditioning and spawning,
rearing larvae and spat, and the production of microalgae to feed all stages of
the production cycle. However, outbreaks of disease continue to be the main
bottleneck for successful larval and spat production, most of them caused by
different representatives of the genus Vibrio. Therefore, attention must be paid
on preventive and management measures that allow the control of such undesirable
bacterial populations. The present review provides an updated picture of the
recently characterized Vibrio species associated with disease of bivalve molluscs
during early stages of development, including the controversial taxonomic
affiliation of some of them and relevant advances in the knowledge of their
virulence determinants. The problematic use of antibiotics, as well as its eco
friendly alternatives are also critically discussed.
PMID- 28515717
TI - The Leaderless Bacteriocin Enterocin K1 Is Highly Potent against Enterococcus
faecium: A Study on Structure, Target Spectrum and Receptor.
AB - Enterocin K1 (EntK1), enterocin EJ97 (EntEJ97), and LsbB are three sequence
related leaderless bacteriocins. Yet LsbB kills only lactococci while EntK1 and
EntEJ97 target wider spectra with EntK1 being particularly active against
Enterococcus faecium, including nosocomial multidrug resistant isolates. NMR
study of EntK1 showed that it had a structure very similar to LsbB - both having
an amphiphilic N-terminal alpha-helix and an unstructured C-terminus. The alpha
helix in EntK1 is, however, about 3-4 residues longer than that of LsbB.
Enterococcal mutants highly resistant to EntEJ97 and EntK1 were found to have
mutations within rseP, a gene encoding a stress response membrane-bound Zn
dependent protease. Heterologous expression of the enterococcal rseP rendered
resistant cells of Streptococcus pneumoniae sensitive to EntK1 and EntEJ97,
suggesting that RseP likely serves as the receptor for EntK1 and EntEJ97. It was
also shown that the conserved proteolytic active site in E. faecalis RseP is
partly required for EntK1 and EntEJ97 activity, since alanine substitutions of
its conserved residues (HExxH) reduced the sensitivity of the clones to the
bacteriocins. RseP is known to be involved in bacterial stress response. As
expected, the growth of resistant mutants with mutations within rseP was severely
affected when they were exposed to higher (stressing) growth temperatures, e.g.,
at 45 degrees C, at which wild type cells still grew well. These findings allow
us to design a hurdle strategy with a combination of the bacteriocin(s) and
higher temperature that effectively kills bacteriocin sensitive bacteria and
prevents the development of resistant cells.
PMID- 28515719
TI - Production of Japanese Encephalitis Virus Antigens in Plants Using Bamboo Mosaic
Virus-Based Vector.
AB - Japanese encephalitis virus (JEV) is among the major threats to public health in
Asia. For disease control and prevention, the efficient production of safe and
effective vaccines against JEV is in urgent need. In this study, we produced a
plant-made JEV vaccine candidate using a chimeric virus particle (CVP) strategy
based on bamboo mosaic virus (BaMV) for epitope presentation. The chimeric virus,
designated BJ2A, was constructed by fusing JEV envelope protein domain III
(EDIII) at the N-terminus of BaMV coat protein, with an insertion of the foot-and
mouth disease virus 2A peptide to facilitate the production of both unfused and
epitope-presenting for efficient assembly of the CVP vaccine candidate. The
strategy allowed stable maintenance of the fusion construct over long-term serial
passages in plants. Immuno-electron microscopy examination and immunization
assays revealed that BJ2A is able to present the EDIII epitope on the surface of
the CVPs, which stimulated effective neutralizing antibodies against JEV
infection in mice. This study demonstrates the efficient production of an
effective CVP vaccine candidate against JEV in plants by the BaMV-based epitope
presentation system.
PMID- 28515722
TI - Corrigendum: Agro-Industrial Wastes for Production of Biosurfactant by Bacillus
subtilis ANR 88 and Its Application in Synthesis of Silver and Gold
Nanoparticles.
AB - [This corrects the article on p. 492 in vol. 8, PMID: 28392783.].
PMID- 28515720
TI - Computational Exploration of Putative LuxR Solos in Archaea and Their Functional
Implications in Quorum Sensing.
AB - LuxR solos are unexplored in Archaea, despite their vital role in the bacterial
regulatory network. They assist bacteria in perceiving acyl homoserine lactones
(AHLs) and/or non-AHLs signaling molecules for establishing intraspecies,
interspecies, and interkingdom communication. In this study, we explored the
potential LuxR solos of Archaea from InterPro v62.0 meta-database employing
taxonomic, probable function, distribution, and evolutionary aspects to decipher
their role in quorum sensing (QS). Our bioinformatics analyses showed that
putative LuxR solos of Archaea shared few conserved domains with bacterial LuxR
despite having less similarity within proteins. Functional characterization
revealed their ability to bind various AHLs and/or non-AHLs signaling molecules
that involve in QS cascades alike bacteria. Further, the phylogenetic study
indicates that Archaeal LuxR solos (with less substitution per site) evolved
divergently from bacteria and share distant homology along with instances of
horizontal gene transfer. Moreover, Archaea possessing putative LuxR solos,
exhibit the correlation between taxonomy and ecological niche despite being the
inhabitant of diverse habitats like halophilic, thermophilic, barophilic,
methanogenic, and chemolithotrophic. Therefore, this study would shed light in
deciphering the role of the putative LuxR solos of Archaea to adapt varied
habitats via multilevel communication with other organisms using QS.
PMID- 28515721
TI - Efficacy of (+)-Lariciresinol to Control Bacterial Growth of Staphylococcus
aureus and Escherichia coli O157:H7.
AB - This study was undertaken to assess the antibacterial potential of a polyphenolic
compound (+)-lariciresinol isolated from Rubia philippinensis against selected
foodborne pathogens Staphylococcus aureus KCTC1621 and Escherichia coli O157:H7.
(+)-Lariciresinol at the tested concentrations (250 MUg/disk) evoked a
significant antibacterial effect as a diameter of inhibition zones (12.1-14.9 mm)
with minimum inhibitory concentration (MIC), and minimum bactericidal
concentration values of 125-250 and 125-250 MUg/mL, respectively. Furthermore,
(+)-lariciresinol at MIC showed reduction in bacterial cell viabilities, efflux
of potassium (K+) ions and release of 260 nm materials against E. coli O157:H7
and S. aureus KCTC1621. Moreover, deteriorated cell wall morphology of E. coli
O157:H7 and S. aureus KCTC1621 cells treated with (+)-lariciresinol at MIC
further confirmed its inhibitory effect against the tested pathogens, suggesting
it to be an alternative means of antimicrobials.
PMID- 28515723
TI - Different Somatic Hypermutation Levels among Antibody Subclasses Disclosed by a
New Next-Generation Sequencing-Based Antibody Repertoire Analysis.
AB - A diverse antibody repertoire is primarily generated by the rearrangement of V,
D, and J genes and subsequent somatic hypermutation (SHM). Class-switch
recombination (CSR) produces various isotypes and subclasses with different
functional properties. Although antibody isotypes and subclasses are considered
to be produced by both direct and sequential CSR, it is still not fully
understood how SHMs accumulate during the process in which antibody subclasses
are generated. Here, we developed a new next-generation sequencing (NGS)-based
antibody repertoire analysis capable of identifying all antibody isotype and
subclass genes and used it to examine the peripheral blood mononuclear cells of
12 healthy individuals. Using a total of 5,480,040 sequences, we compared
percentage frequency of variable (V), junctional (J) sequence, and a combination
of V and J, diversity, length, and amino acid compositions of CDR3, SHM, and
shared clones in the IgM, IgD, IgG3, IgG1, IgG2, IgG4, IgA1, IgE, and IgA2 genes.
The usage and diversity were similar among the immunoglobulin (Ig) subclasses.
Clonally related sequences sharing identical V, D, J, and CDR3 amino acid
sequences were frequently found within multiple Ig subclasses, especially between
IgG1 and IgG2 or IgA1 and IgA2. SHM occurred most frequently in IgG4, while IgG3
genes were the least mutated among all IgG subclasses. The shared clones had
almost the same SHM levels among Ig subclasses, while subclass-specific clones
had different levels of SHM dependent on the genomic location. Given the
sequential CSR, these results suggest that CSR occurs sequentially over multiple
subclasses in the order corresponding to the genomic location of IGHCs, but CSR
is likely to occur more quickly than SHMs accumulate within Ig genes under
physiological conditions. NGS-based antibody repertoire analysis should provide
critical information on how various antibodies are generated in the immune
system.
PMID- 28515724
TI - An Analysis of Trafficking Receptors Shows that CD44 and P-Selectin Glycoprotein
Ligand-1 Collectively Control the Migration of Activated Human T-Cells.
AB - Selectins guide the traffic of activated T-cells through the blood stream by
mediating their tethering and rolling onto inflamed endothelium, in this way
acting as beacons to help navigate them to sites of inflammation. Here, we
present a comprehensive analysis of E-selectin ligands expressed on activated
human T-cells. We identified several novel glycoproteins that function as E
selectin ligands. Specifically, we compared the role of P-selectin glycoprotein
ligand-1 (PSGL-1) and CD43, known E-selectin ligands, to CD44, a ligand that has
not previously been characterized as an E-selectin ligand on activated human T
cells. We showed that CD44 acts as a functional E-selectin ligand when expressed
on both CD4+ and CD8+ T-cells. Moreover, the CD44 protein carries a binding
epitope identifying it as hematopoietic cell E- and/or L-selectin ligand (HCELL).
Furthermore, by knocking down these ligands individually or together in primary
activated human T-cells, we demonstrated that CD44/HCELL, and not CD43,
cooperates with PSGL-1 as a major E-selectin ligand. Additionally, we
demonstrated the relevance of our findings to chronic autoimmune disease, by
showing that CD44/HCELL and PSGL-1, but not CD43, from T-cells isolated from
psoriasis patients, bind E-selectin.
PMID- 28515728
TI - Corrigendum: Increased Toll-Like Receptors Activity and TLR Ligands in Patients
with Autoimmune Thyroid Diseases.
AB - [This corrects the article on p. 578 in vol. 7, PMID: 28018345.].
PMID- 28515729
TI - Growth and Yield Responses of Cowpea to Inoculation and Phosphorus Fertilization
in Different Environments.
AB - Cowpea (Vigna unguiculata) is a major source of dietary protein and essential
component of the cropping systems in semi-arid regions of Sub-Saharan Africa.
However, yields are very low due to lack of improved cultivars, poor management
practices, and limited inputs use. The objectives of this study were to assess
the effects of rhizobia inoculant and P on nodulation, N accumulation and yield
of two cowpea cultivars in Mozambique. Field study was conducted in three
contrasting environments during the 2013/2014 and 2014/2015 seasons using
randomized complete block design with four replications and four treatments.
Treatments consisted of seed inoculation, application of 40 kg P2O5 ha-1,
inoculation + P, and a non-inoculated control. The most probable number (MPN)
technique was used to estimate the indigenous bradyrhizobia populations at the
experimental sites. The rhizobia numbers at the sites varied from 5.27 * 102 to
1.07 * 103 cells g-1 soil. Inoculation increased nodule number by 34-76% and
doubled nodule dry weight (78 to 160 mg plant-1). P application improved
nodulation and interacted positively with the inoculant. Inoculation, P, and
inoculant + P increased shoot dry weight, and shoot and grain N content across
locations but increases in number of pods plant-1, seeds pod-1, and 100-seed
weight were not consistent among treatments across locations. Shoot N content was
consistently high for the inoculated plants and also for the inoculated + P
fertilized plants, whereas the non-inoculated control plants had the lowest
tissue N content. P uptake in shoot ranged from 1.72 to 3.77 g kg-1 and was
higher for plants that received P fertilizer alone. Inoculation and P either
alone or in combination consistently increased cowpea grain yield across
locations with yields ranging from 1097 kg ha-1 for the non-inoculated control to
1674 kg ha-1 for the inoculant + P treatment. Grain protein concentration
followed a similar trend as grain yield and ranged from 223 to 252 g kg-1 but a
negative correlation between grain yield and protein concentration was observed.
Inoculation increased net returns by $104-163 ha-1 over that for the control. The
results demonstrate the potential of improving cowpea grain yield, quality and
profitability using inoculant, although the cost-benefit for using P at the
current fertilizer price is not attractive except when applied together with
inoculant at low P site.
PMID- 28515725
TI - Application of Zebrafish Models in Inflammatory Bowel Disease.
AB - Inflammatory bowel disease (IBD) is a chronic, recurrent, and remitting
inflammatory disease with unclear etiology. As a clinically frequent disease, it
can affect individuals throughout their lives, with multiple complications.
Unfortunately, traditional murine models are not efficient for the further study
of IBD. Thus, effective and convenient animal models are needed. Zebrafish have
been used as model organisms to investigate IBD because of their suggested highly
genetic similarity to humans and their superiority as laboratory models. The
zebrafish model has been used to study the composition of intestinal microbiota,
novel genes, and therapeutic approaches. The pathogenesis of IBD is still unclear
and many risk factors remain unidentified. In this review, we compare traditional
murine models and zebrafish models in terms of advantages, pathogenesis, and drug
discovery screening for IBD. We also review the progress and deficiencies of the
zebrafish model for scientific applications.
PMID- 28515727
TI - Basics of Radiation Biology When Treating Hyperproliferative Benign Diseases.
AB - For decades, low- and moderate-dose radiation therapy (RT) has been shown to
exert a beneficial therapeutic effect in a multitude of non-malignant conditions
including painful degenerative muscoloskeletal and hyperproliferative disorders.
Dupuytren and Ledderhose diseases are benign fibroproliferative diseases of the
hand/foot with fibrotic nodules and fascial cords, which determine debilitating
contractures and deformities of fingers/toes, while keloids are exuberant scar
formations following burn damage, surgery, and trauma. Although RT has become an
established and effective option in the management of these diseases,
experimental studies to illustrate cellular composites and factors involved
remain to be elucidated. More recent findings, however, indicate the involvement
of radiation-sensitive targets like mitotic fibroblasts/myofibroblasts as well as
inflammatory cells. Radiation-related molecular mechanisms affecting these target
cells include the production of free radicals to hamper proliferative activity
and interference with growth factors and cytokines. Moreover, an impairment of
activated immune cells involved in both myofibroblast proliferative and
inflammatory processes may further contribute to the clinical effects. We here
aim at briefly describing mechanisms contributing to a modulation of
proliferative and inflammatory processes and to summarize current concepts of
treating hyperproliferative diseases by low and moderate doses of ionizing
radiation.
PMID- 28515730
TI - Analysis of MADS-Box Gene Family Reveals Conservation in Floral Organ ABCDE Model
of Moso Bamboo (Phyllostachys edulis).
AB - Mini chromosome maintenance 1, agamous, deficiens, and serum response factor
(MADS)-box genes are transcription factors which play fundamental roles in flower
development and regulation of floral organ identity. However, till date,
identification and functions of MADS-box genes remain largely unclear in
Phyllostachys edulis. In view of this, we performed a whole-genome survey and
identified 34 MADS-box genes in P. edulis, and based on phylogeny, they were
classified as MIKCC, MIKC*, Malpha, and Mbeta. The detailed analysis about gene
structure and motifs, phylogenetic classification, comparison of gene divergence
and duplication are provided. Interestingly, expression patterns for most genes
were found similar to those of Arabidopsis and rice, indicating that the well
established ABCDE model can be applied to P. edulis. Moreover, we overexpressed
PheMADS15, an AP1-like gene, in Arabidopsis, and found that the transgenic plants
have early flowering phenotype, suggesting that PheMADS15 might be a regulator of
flowering transition in P. edulis. Taken together, this study provides not only
insightful comprehension but also useful information for understanding the
functions of MADS-box genes in P. edulis.
PMID- 28515726
TI - Comparative Analysis of Immune Checkpoint Molecules and Their Potential Role in
the Transmissible Tasmanian Devil Facial Tumor Disease.
AB - Immune checkpoint molecules function as a system of checks and balances that
enhance or inhibit immune responses to infectious agents, foreign tissues, and
cancerous cells. Immunotherapies that target immune checkpoint molecules,
particularly the inhibitory molecules programmed cell death 1 and cytotoxic T
lymphocyte-associated protein 4 (CTLA-4), have revolutionized human oncology in
recent years, yet little is known about these key immune signaling molecules in
species other than primates and rodents. The Tasmanian devil facial tumor disease
is caused by transmissible cancers that have resulted in a massive decline in the
wild Tasmanian devil population. We have recently demonstrated that the
inhibitory checkpoint molecule PD-L1 is upregulated on Tasmanian devil
(Sarcophilus harrisii) facial tumor cells in response to the interferon-gamma
cytokine. As this could play a role in immune evasion by tumor cells, we
performed a thorough comparative analysis of checkpoint molecule protein
sequences among Tasmanian devils and eight other species. We report that many of
the key signaling motifs and ligand-binding sites in the checkpoint molecules are
highly conserved across the estimated 162 million years of evolution since the
last common ancestor of placental and non-placental mammals. Specifically, we
discovered that the CTLA-4 (MYPPPY) ligand-binding motif and the CTLA-4 (GVYVKM)
inhibitory domain are completely conserved across all nine species used in our
comparative analysis, suggesting that the function of CTLA-4 is likely conserved
in these species. We also found that cysteine residues for intra- and
intermolecular disulfide bonds were also highly conserved. For instance, all 20
cysteine residues involved in disulfide bonds in the human 4-1BB molecule were
also present in devil 4-1BB. Although many key sequences were conserved, we have
also identified immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and
immunoreceptor tyrosine-based switch motifs (ITSMs) in genes and protein domains
that have not been previously reported in any species. This checkpoint molecule
analysis and review of salient features for each of the molecules presented here
can serve as road map for the development of a Tasmanian devil facial tumor
disease immunotherapy. Finally, the strategies can be used as a guide for
veterinarians, ecologists, and other researchers willing to venture into the
nascent field of wild immunology.
PMID- 28515731
TI - Ectopic Expression of CDF3 Genes in Tomato Enhances Biomass Production and Yield
under Salinity Stress Conditions.
AB - Cycling Dof Factor (CDF) transcription factors (TFs) are involved in multiple
processes related to plant growth and development. A member of this family, CDF3,
has recently been linked in Arabidopsis to the regulation of primary metabolism
and abiotic stress responses, but its role in crop production under stress is
still unknown. In this study, we characterized tomato plants overexpressing the
CDF3 genes from Arabidopsis and tomato and analyzed their effects on growth and
yield under salinity, additionally gaining deeper insights into the molecular
function of these TFs. Our results provide evidence for higher biomass production
and yield in the 35S::AtCDF3 and 35S::SlCDF3 plants, likely due to a higher
photosynthetic capacity resulting in increased sucrose availability.
Transcriptome analysis revealed that CDF3 genes regulate a set of genes involved
in redox homeostasis, photosynthesis performance and primary metabolism that lead
to enhanced biomass production. Consistently, metabolomic profiling revealed that
CDF3 evokes changes in the primary metabolism triggering enhanced nitrogen
assimilation, and disclosed that the amount of some protective metabolites
including sucrose, GABA and asparagine were higher in vegetative tissues of CDF3
overexpressing plants. Altogether these changes improved performance of
35S::AtCDF3 and 35S::SlCDF3 plants under salinity conditions. Moreover, the
overexpression of CDF3 genes modified organic acid and sugar content in fruits,
improving variables related to flavor perception and fruit quality. Overall, our
results associate the CDF3 TF with a role in the control of growth and C/N
metabolism, and highlight that overexpression of CDF3 genes can substantially
improve plant yield.
PMID- 28515732
TI - Osmotic Stress Induced Cell Death in Wheat Is Alleviated by Tauroursodeoxycholic
Acid and Involves Endoplasmic Reticulum Stress-Related Gene Expression.
AB - Although, tauroursodeoxycholic acid (TUDCA) has been widely studied in mammalian
cells because of its role in inhibiting apoptosis, its effects on plants remain
almost unknown, especially in the case of crops such as wheat. In this study, we
conducted a series of experiments to explore the effects and mechanisms of action
of TUDCA on wheat growth and cell death induced by osmotic stress. Our results
show that TUDCA: (1) ameliorates the impact of osmotic stress on wheat height,
fresh weight, and water content; (2) alleviates the decrease in chlorophyll
content as well as membrane damage caused by osmotic stress; (3) decreases the
accumulation of reactive oxygen species (ROS) by increasing the activity of
antioxidant enzymes under osmotic stress; and (4) to some extent alleviates
osmotic stress-induced cell death probably by regulating endoplasmic reticulum
(ER) stress-related gene expression, for example expression of the basic leucine
zipper genes bZIP60B and bZIP60D, the binding proteins BiP1 and BiP2, the protein
disulfide isomerase PDIL8-1, and the glucose-regulated protein GRP94. We also
propose a model that illustrates how TUDCA alleviates osmotic stress-related
wheat cell death, which provides an important theoretical basis for improving
plant stress adaptation and elucidates the mechanisms of ER stress-related plant
osmotic stress resistance.
PMID- 28515734
TI - Plant Growth under Natural Light Conditions Provides Highly Flexible Short-Term
Acclimation Properties toward High Light Stress.
AB - Efficient acclimation to different growth light intensities is essential for
plant fitness. So far, most studies on light acclimation have been conducted with
plants grown under different constant light regimes, but more recent work
indicated that acclimation to fluctuating light or field conditions may result in
different physiological properties of plants. Thale cress (Arabidopsis thaliana)
was grown under three different constant light intensities (LL: 25 MUmol photons
m-2 s-1; NL: 100 MUmol photons m-2 s-1; HL: 500 MUmol photons m-2 s-1) and under
natural fluctuating light (NatL) conditions. We performed a thorough
characterization of the morphological, physiological, and biochemical properties
focusing on photo-protective mechanisms. Our analyses corroborated the known
properties of LL, NL, and HL plants. NatL plants, however, were found to combine
characteristics of both LL and HL grown plants, leading to efficient and unique
light utilization capacities. Strikingly, the high energy dissipation capacity of
NatL plants correlated with increased dynamics of thylakoid membrane
reorganization upon short-term acclimation to excess light. We conclude that the
thylakoid membrane organization and particularly the light-dependent and
reversible unstacking of grana membranes likely represent key factors that
provide the basis for the high acclimation capacity of NatL grown plants to
rapidly changing light intensities.
PMID- 28515733
TI - Stable Internal Reference Genes for Normalizing Real-Time Quantitative PCR in
Baphicacanthus cusia under Hormonal Stimuli and UV Irradiation, and in Different
Plant Organs.
AB - Baphicacanthus cusia (Nees) Bremek, the plant source for many kinds of drugs in
traditional Chinese medicine, is widely distributed in South China, especially in
Fujian. Recent studies about B. cusia mainly focus on its chemical composition
and pharmacological effects, but further analysis of the plant's gene functions
and expression is required to better understand the synthesis of its effective
compounds. Real-time quantitative polymerase chain reaction (RT-qPCR) is a
powerful method for gene expression analysis. It is necessary to select a
suitable reference gene for expression normalization to ensure the accuracy of RT
qPCR results. Ten candidate reference genes were selected from the transcriptome
datasets of B. cusia in this study, and the expression stability was assessed
across 60 samples representing different tissues and organs under various
conditions, including ultraviolet (UV) irradiation, hormonal stimuli (jasmonic
acid methyl ester and abscisic acid), and in different plant organs. By employing
different algorithms, such as geNorm, NormFinder, and BestKeeper, which are
complementary approaches based on different statistical procedures, 18S rRNA was
found to be the most stable gene under UV irradiation and hormonal stimuli,
whereas ubiquitin-conjugating enzyme E2 was the best suitable gene for different
plant organs. This novel study aimed to screen for suitable reference genes and
corresponding primer pairs specifically designed for gene expression studies in
B. cusia, in particular for RT-qPCR analyses.
PMID- 28515736
TI - Expression of Key Structural Genes of the Phenylpropanoid Pathway Associated with
Catechin Epimerization in Tea Cultivars.
AB - Catechin epimerization is an important factor affecting tea catechin compositions
and thereby tea quality. However, a lack of tea germplasms with high non
epicatechins limits relative research. Here, a tea cultivar Y510 with high non
epicatechins was firstly reported and used for catechin and RNA sequencing (RNA
Seq) analysis. Results showed that the (-)-gallocatechin gallate and (+)-catechin
(C) contents in Y510 were at least 136 and 6 times higher than those in
Fudingdabaicha and 0306I, but the epicatechins (-)-epigallocatechin and (-)
epicatechin (EC) were significantly lower. Eleven unigenes potentially involved
in catechin epimerization were identified by RNA-Seq analysis. Based on a
combination of catechin and gene expression analysis, it was hypothesized that
two anthocyanidin reductase genes (CsANR1, CsANR2) and an anthocyanidin synthase
gene (CsANS) are the key genes affecting catechin epimerization in tea. Non
epicatechin formations were hypothesized to be mainly influenced by the
expression ratio of CsANR2 to CsANR1 and the expression of CsANS. Overexpression
of CsANS in an Arabidopsis mutant tds4-2 led to a significant increase of EC
accumulation in seeds, revealing CsANS is important for catechin epimerization.
These results shed new light on breeding tea cultivars with special catechin
compositions.
PMID- 28515737
TI - The Complete Plastome Sequences of Four Orchid Species: Insights into the
Evolution of the Orchidaceae and the Utility of Plastomic Mutational Hotspots.
AB - Orchidaceae (orchids) is the largest family in the monocots, including about
25,000 species in 880 genera and five subfamilies. Many orchids are highly valued
for their beautiful and long-lasting flowers. However, the phylogenetic
relationships among the five orchid subfamilies remain unresolved. The major
dispute centers on whether the three one-stamened subfamilies, Epidendroideae,
Orchidoideae, and Vanilloideae, are monophyletic or paraphyletic. Moreover,
structural changes in the plastid genome (plastome) and the effective genetic
loci at the species-level phylogenetics of orchids have rarely been documented.
In this study, we compared 53 orchid plastomes, including four newly sequenced
ones, that represent four remote genera: Dendrobium, Goodyera, Paphiopedilum, and
Vanilla. These differ from one another not only in their lengths of inverted
repeats and small single copy regions but also in their retention of ndh genes.
Comparative analyses of the plastomes revealed that the expansion of inverted
repeats in Paphiopedilum and Vanilla is associated with a loss of ndh genes. In
orchid plastomes, mutational hotspots are genus specific. After having carefully
examined the data, we propose that the three loci 5'trnK-rps16, trnS-trnG, and
rps16-trnQ might be powerful markers for genera within Epidendroideae, and clpP
psbB and rps16-trnQ might be markers for genera within Cypripedioideae. After
analyses of a partitioned dataset, we found that our plastid phylogenomic trees
were congruent in a topology where two one-stamened subfamilies (i.e.,
Epidendroideae and Orchidoideae) were sisters to a multi-stamened subfamily
(i.e., Cypripedioideae) rather than to the other one-stamened subfamily
(Vanilloideae), suggesting that the living one-stamened orchids are paraphyletic.
PMID- 28515735
TI - Time-Course Transcriptome Analysis of Compatible and Incompatible Pollen-Stigma
Interactions in Brassica napus L.
AB - Brassica species exhibit both compatible and incompatible pollen-stigma
interactions, however, the underlying molecular mechanisms remain largely
unknown. Here, RNA-seq technology was applied in a comprehensive time-course
experiment (2, 5, 10, 20, and 30 min) to explore gene expression during
compatible/incompatible pollen-stigma interactions in stigma. Moderate changes of
gene expression were observed both in compatible pollination (PC) and
incompatible pollination (PI) within 10 min, whereas drastic changes showed up by
30 min, especially in PI. Stage specific DEGs [Differentially Expressed Gene(s)]
were identified, and signaling pathways such as stress response, defense
response, cell wall modification and others were found to be over-represented. In
addition, enriched genes in all samples were analyzed as well, 293 most highly
expressed genes were identified and annotated. Gene Ontology and metabolic
pathway analysis revealed 10 most highly expressed genes and 37 activated
metabolic pathways. According to the data, downstream components were activated
in signaling pathways of both compatible and incompatible responses, and
incompatible response had more complicated signal transduction networks. This
study provides more detailed molecular information at different time points after
compatible and incompatible pollination, deepening our knowledge about pollen
stigma interactions.
PMID- 28515667
TI - Measurement of azimuthal correlations of D mesons with charged particles in pp
collisions at [Formula: see text] TeV and p-Pb collisions at [Formula: see text]
TeV.
AB - The azimuthal correlations of D mesons with charged particles were measured with
the ALICE apparatus in pp collisions at [Formula: see text] and p-Pb collisions
at [Formula: see text] at the Large Hadron Collider. [Formula: see text],
[Formula: see text], and [Formula: see text] mesons and their charge conjugates
with transverse momentum [Formula: see text] and rapidity in the nucleon-nucleon
centre-of-mass system [Formula: see text] (pp collisions) and [Formula: see text]
(p-Pb collisions) were correlated to charged particles with [Formula: see text].
The yield of charged particles in the correlation peak induced by the jet
containing the D meson and the peak width are compatible within uncertainties in
the two collision systems. The data are described within uncertainties by Monte
Carlo simulations based on PYTHIA, POWHEG, and EPOS 3 event generators.
PMID- 28515739
TI - Patterns of Inter-Chromosomal Gene Conversion on the Male-Specific Region of the
Human Y Chromosome.
AB - The male-specific region of the human Y chromosome (MSY) is characterized by the
lack of meiotic recombination and it has long been considered an evolutionary
independent region of the human genome. In recent years, however, the idea that
human MSY did not have an independent evolutionary history begun to emerge with
the discovery that inter-chromosomal gene conversion (ICGC) can modulate the
genetic diversity of some portions of this genomic region. Despite the study of
the dynamics of this molecular mechanism in humans is still in its infancy, some
peculiar features and consequences of it can be summarized. The main effect of
ICGC is to increase the allelic diversity of MSY by generating a significant
excess of clustered single nucleotide polymorphisms (SNPs) (defined as groups of
two or more SNPs occurring in close proximity and on the same branch of the Y
phylogeny). On the human MSY, 13 inter-chromosomal gene conversion hotspots
(GCHs) have been identified so far, involving donor sequences mainly from the X
chromosome and, to a lesser extent, from autosomes. Most of the GCHs are
evolutionary conserved and overlap with regions involved in aberrant X-Y crossing
over. This review mainly focuses on the dynamics and the current knowledge
concerning the recombinational landscape of the human MSY in the form of ICGC, on
how this molecular mechanism may influence the evolution of the MSY, and on how
it could affect the information enclosed within a genomic region which, until
recently, appeared to be an evolutionary independent unit.
PMID- 28515738
TI - Chloroplast ATP Synthase Modulation of the Thylakoid Proton Motive Force:
Implications for Photosystem I and Photosystem II Photoprotection.
AB - In wild type plants, decreasing CO2 lowers the activity of the chloroplast ATP
synthase, slowing proton efflux from the thylakoid lumen resulting in buildup of
thylakoid proton motive force (pmf). The resulting acidification of the lumen
regulates both light harvesting, via the qE mechanism, and photosynthetic
electron transfer through the cytochrome b6f complex. Here, we show that the cfq
mutant of Arabidopsis, harboring single point mutation in its gamma-subunit of
the chloroplast ATP synthase, increases the specific activity of the ATP synthase
and disables its down-regulation under low CO2. The increased thylakoid proton
conductivity (gH+) in cfq results in decreased pmf and lumen acidification,
preventing full activation of qE and more rapid electron transfer through the b6f
complex, particularly under low CO2 and fluctuating light. These conditions favor
the accumulation of electrons on the acceptor side of PSI, and result in severe
loss of PSI activity. Comparing the current results with previous work on the
pgr5 mutant suggests a general mechanism where increased PSI photodamage in both
mutants is caused by loss of pmf, rather than inhibition of CEF per se. Overall,
our results support a critical role for ATP synthase regulation in maintaining
photosynthetic control of electron transfer to prevent photodamage.
PMID- 28515741
TI - Respiratory functional status after conventional and minimally invasive aortic
valve replacement surgery - a propensity score analysis.
AB - INTRODUCTION: Reports describing respiratory function of patients after
conventional or minimally invasive cardiac surgery are infrequent. AIM: To
compare pulmonary functional status after conventional (AVR) and after minimally
invasive, through right anterior minithoracotomy, aortic valve replacement (RT
AVR). MATERIAL AND METHODS: This was an observational analysis of 212 patients
scheduled for RT-AVR and 212 for AVR between January 2011 and December 2014
selected using propensity score matching. Respiratory function based on
spirometry examinations is presented. RESULTS: Hospital mortality was 1.4% in RT
AVR and 1.9% in AVR (p = 0.777). Predicted mortality (EuroSCORE II) was 3.2 +/
1.1% in RT-AVR and 3.1 +/-1.6% in AVR (p = 0.298). Mechanical ventilation time in
intensive care unit (ICU) was 7.3 +/-3.9 h for RT-AVR and 9.6 +/-5.5 h for AVR
patients (p < 0.001). Seven days and 1 month after surgery, the reduction of
spirometry functional tests was greater in the AVR group than in the RT-AVR group
(p < 0.001). Three months after surgery, all spirometry parameters were still
reduced and had not returned to preoperative values in both RT-AVR and AVR
groups. However, the difference in spirometry values was no longer statistically
significant between RT-AVR and AVR groups. Presence of chronic obstructive
pulmonary disease and conventional AVR surgical technique were associated with
lower values of spirometry parameters after surgery in linear median regression.
CONCLUSIONS: Respiratory function based on spirometry examinations was less
impaired after minimally invasive RT-AVR surgery in comparison to conventional
AVR surgery through median sternotomy.
PMID- 28515742
TI - The use of intraoperative epiaortic ultrasonography in monitoring patients over
75 years old treated with aortic valve replacement.
AB - INTRODUCTION: Epiaortic ultrasound scanning (EAS) extended the use of ultrasound
to the intraoperative diagnosis of aortic pathology. Surgical palpation of the
ascending aorta underestimates the presence and severity of atherosclerotic
plaques. Epiaortic ultrasound scanning has been used as an adjunct to
transesophageal echocardiography (TEE) or as a primary direct diagnostic tool for
imaging the ascending aorta as well as the aortic arch, which gained prominence
as part of a multipronged intraoperative strategy to reduce atherosclerotic
emboli. AIM: To compare the epiaortic examination with transthoracic and
transesophageal echo (transthoracic echocardiography (TTE) and TEE), X-ray,
surgical intraoperative palpation, and postoperative neurological status.
MATERIAL AND METHODS: The analyzed group consisted of 35 patients (mean age: 81.3
years) treated with aortic valve replacement (AVR), either alone (60%) or
combined with coronary artery bypass grafting (CABG; 22.8%) or aortic aneurysm
replacement (11.42%). In 2 patients, only CABG was performed because
intraoperatively reevaluated strategy. Thierteen patients have got a history of
diabetes, 10 chronic renal failure and 3 of cerebral stroke. RESULTS: In more
than 80% of patients, positive EAS results had an influence on the choice of
aortic clamping site and in 50% of patients on the site of cannulation. Female
sex, peripheral vascular disease, history of previous stroke, and calcifications
in the ascending aorta in TTE have significant predictive value for recognizing
atherosclerotic changes in EAS and the risk of postoperative neurological
complications in octogenarians treated with AVR. CONCLUSIONS: Epiaortic
ultrasound scanning imaging is superior to TTE and manual palpation in the
detection and localization of ascending atherosclerosis. This technique should be
introduced as a standard perioperative examination in older patients at risk of
neurological complications.
PMID- 28515740
TI - Left atrial appendage occlusion procedures.
PMID- 28515744
TI - Mycobacterium chimaera - a new threat for cardiac surgical patients?
AB - An outbreak of invasive Mycobacterium chimaera infections associated with "heater
cooler" devices in patients treated with cardiac surgery has been described
worldwide. The authors summarize the current state of knowledge regarding the
epidemiology, diagnostics, treatment, and prevention of Mycobacterium chimaera
infections in patients after cardiothoracic surgery.
PMID- 28515745
TI - New aspects in the diagnosis and treatment of primary spontaneous pneumothorax.
AB - This paper provides a recapitulation of the position of the British Thoracic
Society and the American College of Chest Physicians based on a review of the
literature concerning the current methods of diagnosing and treating primary
spontaneous pneumothorax (PSP). The previously developed guidelines were re
evaluated in 2015 by a task force of the European Respiratory Society (ERS). They
are intended to be used by surgeons as well as emergency and pulmonary ward
physicians, and they apply largely to emergency procedures. In recent years, the
effectiveness of minimally invasive methods (punctures, drainage) in combination
with talc pleurodesis for the initial therapy of PSP has been recognized. The
efficacy of thoracoscopy (VATS) for the treatment of this disease has been proven
by the development of minimally invasive surgical techniques in thoracic surgery.
This paper also discusses the efficacy of the surgical methods available.
PMID- 28515743
TI - Acute-phase proteins and oxidative stress in patients undergoing coronary artery
bypass graft: comparison of cardioplegia strategy.
AB - INTRODUCTION: Several strategies are still being introduced to cardiac surgery
techniques to reduce the signs of the inflammatory response and oxidative stress.
Many efforts have been made to develop the best possible method for myocardial
protection. AIM: To assess the effect of the cardioplegia strategy on the
systemic inflammatory response and oxidative stress. MATERIAL AND METHODS: A
group of 238 consecutive, elective on-pump coronary artery bypass graft patients
(CABG; 183 men, aged 64.6 +/-8.1 years) were prospectively studied. Patients were
enrolled in two groups: with warm blood cardioplegia (n = 124) and with cold
crystalloid cardioplegia (n = 114). In each group, pre- and postoperative levels
of plasma C-reactive protein, fibrinogen, interleukin 6 and 8-iso-prostaglandin
F2alpha (8-iso-PGF2alpha) were measured. RESULTS: All studied markers
significantly increased 18-36 h following CABG and then decreased in 5-7
postoperative days but remained above baseline levels. No differences in terms of
studied markers and clinical outcomes were noted for the different types of
cardioplegia. Regression analysis showed a significant correlation between
preoperative level of oxidative stress measured by 8-iso-PGF2alpha and
postoperative myocardial infarction as well as in-hospital cardiovascular death
(p = 0.047 and p = 0.041 respectively). CONCLUSIONS: This study extends previous
reports by showing that the type of cardioplegia does not affect the systemic
inflammatory response or oxidative stress, which are associated with the CABG
procedure. It might be speculated that preoperative screening of oxidative stress
could be helpful in identifying patients at increased risk of an unfavorable
course after CABG.
PMID- 28515746
TI - Veno-arterial extracorporeal membrane oxygenation as cardiogenic shock therapy
support in adult patients after heart surgery.
AB - INTRODUCTION: The authors present their personal experience in qualifying and
treating adult patients using veno-arterial (VA) extracorporeal membrane
oxygenation (ECMO) in postcardiotomy cardiogenic shock. AIM: The aim of this
study was to analyze the results of VA ECMO in patients with postcardiotomy
cardiogenic shock. An analysis of the risk factors of postoperative mortality was
also performed. MATERIAL AND METHODS: We analyzed the perioperative results of
survivors and non-survivors of treatment using VA ECMO. We compared the number of
days on VA ECMO therapy, types of cardiac surgical procedures, and the frequency
of VA ECMO complications such as coagulation disorders, lower limb ischemia,
cardiac tamponade, and renal replacement therapy. RESULTS: There were 27 patients
treated with VA ECMO during the study period. The mean patient age was 45 +/-16
years. The hospital mortality rate of patients treated with VA ECMO therapy was
70% (19/27). There were no significant differences between the groups of
survivors and non-survivors regarding age, gender, admission type and coexisting
diseases. Type of cardiac surgical procedure had no influence on mortality or
complications of therapy using VA ECMO. CONCLUSIONS: The VA ECMO can be an
effective form of therapy in some patients in postcardiotomy cardiogenic shock.
PMID- 28515748
TI - Effects of propolis on warfarin efficacy.
AB - INTRODUCTION: Warfarin is commonly used to avoid thromboembolism, predominantly
for cardiovascular pathologies. However, the consumption of several herbal
products is not permitted during its use due to the associated interactions.
Propolis is a popular phytotherapy product made by honey bees. The use of
propolis has been dramatically increasing in recent times. AIM: To evaluate the
possible interactions between propolis and warfarin in a mouse model with
determination of the international normalized ratio (INR) values. MATERIAL AND
METHODS: CD-1 mice were employed in the experimental model. The mice were
warfarinized, and propolis was administered simultaneously. The INR values were
obtained. All animals were sacrificed at the end of the study. RESULTS: The
baseline INR value was 0.8 +/-0.1. After 72 h, the INR value increased as
expected. The INR value was 7.28 +/-1.08 in the control group and 5.8 +/-2.88 in
the propolis group. At the end of the study, the INR value was 1.3 +/-0.37.
Propolis interacted with warfarin and caused a decrease in the INR value.
CONCLUSIONS: Propolis interactions, especially with warfarin, should be kept in
mind and further studied. Healthcare specialists should be aware of this possible
interaction between warfarin and propolis and inform patients about it.
PMID- 28515747
TI - Revascularization in ischemic heart failure with reduced left ventricular
ejection fraction. The impact of complete revascularization.
AB - Heart failure is a growing problem worldwide, with coronary artery disease being
the underlying cause of over two-thirds of cases. Revascularization in this group
of patients may potentially inhibit the progressive damage to the myocardium and
lead to improved outcomes, but data in this area are scarce. This article
emphasizes the role of qualification for revascularization and selection of
method (percutaneous coronary intervention vs. coronary artery bypass grafting)
and subsequently focuses on the issue of completeness of revascularization in
this group of patients.
PMID- 28515751
TI - Malignant triton tumor of the lung, infiltrating the left atrium and left
ventricle, with metastasis to the small intestine.
AB - Malignant triton tumors are a rare subtype of malignant peripheral nerve sheath
tumors showing rhabdomyosarcomatous differentiation. We report the case of a 33
year-old patient who underwent an excision of such a tumor by thoracic and
cardiac surgery. He was reoperated on 1 month later because of a tumor of the
small intestine and received adjuvant radiation.
PMID- 28515749
TI - Thromboembolic complications after an ankle joint open fracture in a patient with
a history of deep vein thrombosis in the lower limbs.
AB - A 55-year-old patient was admitted to the Department of Orthopedics due to an
open fracture in the right ankle joint. On the seventh day of hospitalization the
patient experienced a transient ischemic attack. During the next day, dyspnea,
chest pain and a 'rider' type pulmonary embolism in the pulmonary trunk occluding
both pulmonary arteries and its branches were diagnosed. The patient was
transferred to the Department of Cardiac Surgery. He underwent pulmonary
embolectomy for massive pulmonary, right and left atrial embolism, and left
ventricular embolism. ASD II was closed during this procedure. Ultrasonography
with Doppler was performed 6 days after the surgery and revealed deep vein
thrombosis, so the patient was transferred to the Department of Vascular Surgery
for temporary inferior vena cava filter placement at the time of orthopedic
surgery. The next day after implantation of the filter, the lower limb was
operated on, and 14 days after orthopedic surgery, the vena cava filter was
removed.
PMID- 28515750
TI - Hiatal hernia after esophagectomy - a report of two cases.
AB - Postoperative hiatal hernia after esophagectomy occurs with a frequency of 0.4
6%, and the local conditions following esophagectomy promote its occurrence. In
the material presented here, hiatal hernia in the form of displacement of the
colon to the mediastinum was established in 0.78% (2/256) of all performed
esophagectomies. Both cases were reoperated successfully.
PMID- 28515752
TI - Extended resection of the trachea in a patient with cicatricial tracheal stenosis
after tracheostomy complicated with esophageal-tracheal fistula and extensive
defect of the frontal tracheal wall.
AB - We present a case of one-stage radical surgical treatment of a 24-year-old female
patient with cicatricial granulating tracheal stenosis after tracheostomy
complicated by esophageal-tracheal fistula and an extensive defect of the
anterior wall of the trachea after numerous unsuccessful attempts to correct the
narrowing of the trachea and eliminate the fistula by endoscopic and open
surgical techniques. The patient underwent extended tracheal resection with end
to-end anastomosis with liquidation of the esophageal-tracheal fistula and
elimination of the defect of the anterior wall of the trachea by cervical access.
PMID- 28515754
TI - Traumatic tension pneumopericardium and amputation of the left main bronchus.
AB - A 27-year-old woman sustained a blunt chest trauma after a car accident. Computed
tomography revealed tension pneumopericardium, bilateral pneumothorax, and a
suspected rupture of the left main bronchus. Emergent pericardial needle
aspiration was successfully performed. Bronchial amputation was confirmed by
bronchofiberoscopy. Despite total detachment of the distal part of the bronchial
tree, the ventilation of the left lung was maintained without air leakage by use
of pleural drains. Bronchial obturation resulted from the injury, and was
effectively treated by bronchoscopic sputum suction at the distal end of the
bronchus. Finally, the patient underwent a left thoracotomy with an end-to-end
bronchial anastomosis. The patient was discharged home on the 32nd day after the
trauma, and no complications were recorded during a 3-month follow-up period.
PMID- 28515755
TI - Common origin of all three coronary arteries from the right sinus of Valsalva -
first case study accompanied by mitral valve prolapse and vein anomaly, second
case study followed by successful percutaneous coronary intervention of right
coronary artery stenosis.
AB - Congenital anomalies of the coronary arteries can be divided into two broad
categories: those that alter myocardial perfusion and those that do not. In
coronary anomalies not altering myocardial perfusion, the coronary arteries
originate from the aorta, but their origins are in unusual positions. Although
myocardial perfusion is normal, the angiographer may have trouble locating them.
Patients with an anomalous left main coronary artery arising from the right sinus
of Valsalva are presented. The diagnosis was made by coronary angiography,
transesophageal echocardiography and multislice computed tomography (MSCT). We
present two cases: the first patient with coronary abnormalities had accompanying
venous anomaly of lower extremities and mitral valve prolapse as well. The second
patient had a history of anterior wall myocardial infarction and angioplasty with
stent implantation. The extraordinary passage of the left coronary artery between
the pulmonary trunk and sternum, undetectable in coronarography, was discovered
due to MSCT.
PMID- 28515756
TI - Left main bronchus separation after blunt trauma.
AB - Tracheobronchial damage is very rare in clinical practice and represents no more
than 1% of all injuries caused by blunt trauma. Nearly 80% of patients die before
reaching the hospital. Most ruptures are observed in the right main bronchus and
are located within 2 cm of the carina trachea. The highest mortality rate applies
to patients with bilateral bronchial injuries. Nonspecific symptoms, additionally
masked by complaints regarding other damaged organs, delay the diagnosis and
surgical treatment. The aim of this article is to present one particular clinical
case and to discuss it in conjunction with a literature review.
PMID- 28515753
TI - Traumatic pneumatocele in an 11-year-old boy - report of a rare case and review
of the literature.
AB - The authors present a case of a pneumatocele associated with blunt trauma in a
child. An 11-year-old boy was admitted to the emergency department after he was
knocked over and his chest was trapped under a soccer goal. Chest computed
tomography (CT) revealed several cavities in the lobes of both lungs. The CT of
the abdomen revealed traumatic laceration of the liver. The patient was treated
conservatively. His condition was stable and subsequently improved. He was
discharged 19 days later. After nine months, a chest radiograph showed complete
resolution of the pneumatocele, and abdominal ultrasound demonstrated complete
resolution of the liver hematoma. A traumatic pneumatocele is a benign lesion
resulting from blunt chest trauma, usually in children and young adults, which
typically requires only conservative treatment. The CT scanning is the most
sensitive method for the detection of traumatic pneumatoceles. All emergency
physicians should be familiar with the diagnosis and management of this
condition, to avoid unnecessary invasive procedures.
PMID- 28515757
TI - Emergency HeartWare Ventricular Assist Device (HVAD) exchange due to pump
thrombosis using minimally invasive technique.
AB - Left ventricular assist device (LVAD) thrombosis remains a dreadful complication
of mechanical circulatory support, with an incidence of 8-12% depending on the
pump type and patient's comorbidities. Fibrinolysis may be considered early in
pump thrombosis, but when contraindicated a pump exchange remains the only
alternative. This short report documents an emergency LVAD exchange in a 55-year
old man who underwent LVAD (HeartWare Inc) implantation in 2013 as a bridge to
transplantation. Four months after the initial surgery, he suffered from a
hemorrhagic stroke despite properly managed anticoagulation. On February 17th,
2017 he was re-admitted with LVAD pump thrombosis. As fibrinolysis was
contraindicated, an emergency pump exchange was performed via a limited thoracic
incision in order to minimize surgical trauma, reduce intraoperative
complications and facilitate immediate post-operative recovery. This report
documents the very first LVAD pump exchange as well as the first one performed
via a minimally invasive approach in Poland.
PMID- 28515758
TI - Medical robots in cardiac surgery - application and perspectives.
AB - Medical robots offer new standards and opportunities for treatment. This paper
presents a review of the literature and market information on the current
situation and future perspectives for the applications of robots in cardiac
surgery. Currently in the United States, only 10% of thoracic surgical procedures
are conducted using robots, while globally this value remains below 1%. Cardiac
and thoracic surgeons use robotic surgical systems increasingly often. The goal
is to perform more than one hundred thousand minimally invasive robotic surgical
procedures every year. A surgical robot can be used by surgical teams on a
rotational basis. The market of surgical robots used for cardiovascular and lung
surgery was worth 72.2 million dollars in 2014 and is anticipated to reach 2.2
billion dollars by 2021. The analysis shows that Poland should have more than 30
surgical robots. Moreover, Polish medical teams are ready for the introduction of
several robots into the field of cardiac surgery. We hope that this market will
accommodate the Polish Robin Heart robots as well.
PMID- 28515759
TI - Department of Pediatric Cardiac Surgery in Gdansk in its new location - previous
activity and perspectives for development.
AB - The Department of Pediatric Cardiac Surgery in Gdansk is the only pediatric
cardiac surgery center in northern Poland providing comprehensive treatment to
children with congenital heart defects. The Department of Pediatric Cardiac
Surgery in Gdansk currently offers a full spectrum of advanced procedures of
modern cardiac surgery and interventional cardiology dedicated to patients from
infancy to adolescence. January 19, 2016 marked the official opening of its new
location.
PMID- 28515760
TI - Retraction notice.
AB - [This retracts the article DOI: 10.5114/kitp.2016.61054.].
PMID- 28515762
TI - Biochemical and histopathological effects of green tea nanoparticles in ironized
mouse model.
AB - Transfusion in the treatment of thalassemia gives rise to iron deposits in many
organs. Since there are many obstacles in the use of deferoxamin (DFO) as an iron
chelating agent, it is important to find another alternative therapy that can act
as iron chelation. The study aims to compare the histopathological pictures of
the heart and spleen in iron-induced rats after administration of DFO and
nanoparticles of green tea extract. The research used experimental research
design with a post-test only control group. Experimental nano green teas were
divided into four treatment groups; no diet, DFO supplementation, nano green tea
supplementation, and a combination of both DFO and green tea. Ferritin and
glutathione peroxides were used as biochemical parameters, and histopathological
pictures of the heart and spleen were recorded. The study showed that there was
significant improvement in the rats receiving DFO and nanoparticles of green tea
compared with the rats in the no diet group. The study also reported that nano
green tea has an effect comparable to DFO.
PMID- 28515763
TI - Poly (ethylene-co-vinyl alcohol)-based polymeric thermo-responsive nanocarriers
for controlled delivery of epirubicin to hepatocellular carcinoma.
AB - In this study, poly(ethylene-co-vinyl alcohol) (EVOH) as a novel biocompatible
polymeric scaffold was surface modified by succinylation to get EVOHS and further
pegylated to improve structural properties using methoxypolyethylene glycol (5000
Da) succinate (PEGS) along with targeting with retinoic acid (RA) to get final
modified active and passive targeted conjugate (PEGS-EVOHS-RA) to evaluate its
ability in carrying and delivery of epirubicin to hepatocellular carcinoma cell
lines in response to varying temperatures. In this regard, the PEGS-EVOHS-RA
conjugate was prepared through the desired chemical reactions and its structure
was confirmed using 1H-NMR and FT-IR spectra. The micelles were prepared from
PEGS-EVOHS-RA by dialysis method. The Particle size and zeta potential were
measured, and entrapment efficacy along with in vitro release efficiency in
different temperatures were also studied. The structural morphology of optimized
nanomicelle was studied by transmission electron microscopy micrographs. The
desired final micelles were evaluated for their toxicity using MTT assay on HepG2
human hepatocellular carcinoma cell lines at normal (37 degrees C) and elevated
temperature (45 degrees C). The results revealed that, as the hydrophilicity of
micelles increased, all characteristic properties improved. Then, these micelles
can be considered as potentially effective thermo responsive delivery systems for
targeted delivery of cytotoxic agents to hepatocellular carcinoma.
PMID- 28515764
TI - The effect of epicatechin on oxidative stress and mitochondrial damage induced by
homocycteine using isolated rat hippocampus mitochondria.
AB - Oxidative stress and mitochondrial dysfunction are the main suggested mechanisms
for neurodegenerative diseases. In this study, we have evaluated the effects of
epicatechin (EC) on mitochondrial damage induced by homocycteine (Hcy) using
isolated rat hippocampus mitochondria in vivo. EC (50 mg/kg) was gavaged daily
for a period of 10 days, starting 5 days prior to Hcy (0.5 MUmol/MUL) intra
hippocampus injection in rats. Mitochondria were isolated from brain by different
centrifuge techniques. Mitochondrial function was assayed by MTT test. Also,
mitochondrial swelling and oxidative stress markers, such as reactive oxygen
species (ROS), lipid peroxidation and glutathione (GSH), were assayed. Hcy
induced mitochondrial dysfunction and swelling. Increase in ROS formation, lipid
peroxidation, and decreased GSH were observed after Hcy treatment in isolated
brain mitochondria. Furthermore, oral administration of EC significantly
decreased the lipid peroxidation and ROS levels and also increased GSH levels.
Also, EC treatment significantly improved mitochondrial function. As EC indicated
protective effects against oxidative stress and mitochondrial damage induced by
Hcy, it is suggested for further trials for prevention or treatments of
neurodegenerative disorders such as Alzheimer disease.
PMID- 28515761
TI - Oligonucleotide aptamers: potential novel molecules against viral hepatitis.
AB - Viral hepatitis, as an international public health concern, seriously affects
communities and health system. In recent years, great strides have been taken for
development of new potential tools against viral hepatitis. Among these efforts,
a valuable strategy introduced new molecules called "aptamers". Aptamers as
potential alternatives for antibodies could be directed against any protein in
infected cells and any components of viral particles. In this review, we will
focus on recent advances in the diagnosis and treatment of viral hepatitis based
on aptamer technology. In recent years, various types of aptamers including RNA
and DNA were introduced against viral hepatitis. Some of these aptamers can be
utilized for early and precise diagnosis of hepatitis infections and other group
selected as therapeutic tools against viral targets. Designing diagnostic and
therapeutic platforms based on aptamer technology is a promising approach in
viral infections. The obtained aptamers in the recent years showed obvious
potential for use as diagnostic and therapeutic tools against viral hepatitis.
Although some modifications to increase the biostability and half-life of
aptamers are underway, it seems these molecules will be a favorable substitute
for monoclonal antibody in near future.
PMID- 28515765
TI - Preparation and in vitro-in vivo evaluation of acyclovir floating tablets.
AB - In the current study, floating dosage form containing acyclovir was developed to
increase its oral bioavailability. Effervescent floating tablets containing 200
mg acyclovir were prepared by direct compression method with three different rate
controlling polymers including Hydroxypropyl methylcellulose K4M, Carbapol 934,
and Polyvinylpyrrolidone. Optimized formulation showed good floating properties
and in vitro drug release characteristics with mean dissolution time and
dissolution efficacy of about 4.76 h and 54.33%, respectively. X-ray radiography
exhibited that the tablet would reside in the stomach for about 5 +/- 0.7 h.
After oral administration of floating tablet containing 200 mg acyclovir, the
Cmax, Tmax , and AUC0-infinity of optimized gastroretentive formulation were
found to be 551 +/- 141 ng/mL, 2.75 +/- 0.25 h and 3761 +/- 909.6 ng/mL/h,
respectively.
PMID- 28515766
TI - Pancreatic protective and hypoglycemic effects of Vitex agnus-castus L. fruit
hydroalcoholic extract in D-galactose-induced aging mouse model.
AB - D-galactose induces pancreatic disorder along with aging mouse model. Vitex agnus
castus (VAC) has potential pancreatic protective effect. Hence, this study was
designed to evaluate the hypoglycemic and pancreas protective effects of VAC
hydroalcoholic extract in D-galactose-induced aging female mice. In the present
experimental study, 72 adult female Naval Medical Research Institute (NMRI) mice
(weighing 30-35 g) were divided into 6 groups of control, VAC hydroalcoholic
extract, D-galactose, D-galactose + VAC hydroalcoholic extract, aged, aged + VAC
hydroalcoholic extract. The aged model was prepared by subcutaneous injection of
D-galactose for 45 days and, VAC hydroalcoholic extract was gavaged twice a day
in the last 7 days. 24 h after the last drug and extract administrations, serum
samples and pancreatic tissues were removed to evaluate experimental and
histological determinations. Serum glucose level decreased in VAC, D-galactose
and, aged-treated groups compared to the control (P < 0.05). Insulin level
increased in VAC and decreased in D-galactose and aged VAC-treated mice compared
to the control (P < 0.05). Homeostasis model assessment-estimated insulin
resistance (HOMA-IR) increased in D-galactose, aging, and VAC hydroalcoholic
extract groups (P < 0.05) and, administration of VAC hydroalcoholic extract
improved HOMA-IR in D-galactose and aging treated animals. Despite the size of
pancreatic islets decreased in aged and D-galactose groups, VAC administration
recovered it. Present data showed that VAC hydroalcoholic extract has
hypoglycemic and pancreatic protective effects in natural aged and aging model
mice.
PMID- 28515767
TI - Cost-effectiveness evaluation of aspirin in primary prevention of myocardial
infarction amongst males with average cardiovascular risk in Iran.
AB - Aspirin is one of the certified medicines commonly used for the secondary
prevention of myocardial infarction (MI). Aspirin side effects and
gastrointestinal bleeding, in particular, have arisen debates on its use for the
primary prevention of MI. The present research evaluates the cost-effectiveness
of the use of aspirin in the primary prevention of MI among Iranian men with
average cardiovascular disease (CVD) risk, using Markov modeling technique. The
incremental cost-effectiveness ratios (ICERs) estimated to be 864 USA dollars
(USD) per quality-adjusted life years (QALY) gained and 782 USD per life years
gained (LYG) for each patient in the base-case scenario (public tariffs and no
discounting). This research proves cost-effectiveness of the use of aspirin in
the primary prevention of MI in targeted population, since the assessed ICERs are
quite under the recommended threshold by WHO which is one gross domestic product
(GDP) per capita ($5315.1 for Iran in 2015).
PMID- 28515769
TI - Inhibitory effects of different fractions of Nepeta satureioides on melanin
synthesis through reducing oxidative stress.
AB - Nepeta satureioides Boiss. has been used in traditional medicine of eastern
countries and is famous for its medicinal properties. The aim of this study was
to evaluate the effect of methanol (MeOH), n-hexane and dichloromethane (CH2Cl2)
fractions of the extract on melanin synthesis and oxidative stress in B16F10
melanoma cell line. The B16F10 cell line viability after treatment with
increasing concentrations of different fractions of the plant (5-60 MUg/mL) was
measured using MTT assay. The inhibitory effect on synthesis of melanin, mushroom
tyrosinase activity, cellular tyrosinase and oxidative stress were determined by
the colorimetric and fluorometric methods. The data showed that at concentrations
below 60 MUg/mL, fractions did not show significant toxicity on melanoma cells.
The amount of melanin synthesis by MeOH and CH2Cl2 fractions and mushroom
tyrosinase activity by the MeOH fraction declined in B16F10 cells. In addition to
the capacity of MeOH, n-hexane and CH2Cl2 fractions in decreasing the amount of
reactive oxygen species (ROS) in melanoma cells, all fractions revealed
remarkable antioxidant activity. The melanogenesis inhibitory and antioxidant
effects of N. satureioides on B16F10 cells may suggest this plant as a new
pharmaceutical agent in reducing skin pigment and skin aging in cosmetic
industry.
PMID- 28515768
TI - Effect of acute and long term potassium bromide administration on spatial working
memory in rat.
AB - Potassium bromide (KBr), an old antiepileptic agent, is illegally used in
pharmaceutical or food industries to improve the product appearance. KBr has been
proven to influence several pathways which are important in memory formation.
Therefore, the present study aimed to evaluate the effect of KBr on spatial
working memory using object recognition task (ORT). Rats received a single dose
of KBr (50, 100 or 150 mg/kg), per oral, in acute treatment. KBr long term
effects were also studied in animals receiving 50 mg/kg/day of KBr for 28
consecutive days. At the end of treatments, animals underwent two trials of ORT,
five min each. In the first trial (T1), animals encountered with two identical
objects for exploration. After 1 h, the animals were exposed to a familiar and an
unfamiliar object (T2). The exploration times for discrimination (D) and
recognition (R) as well as the frequency of exploration for any objects were
determined. Acute administration of 150 mg/kg of KBr significantly decreased the
discrimination and recognition indices (RI and DI) (P < 0.01) compared to the
control. However, lower doses failed to influence the animals' performance in the
test. In addition, long term administration of KBr remarkably diminished the DI
and RI and the frequency of exploration (P < 0.05). The results of this study
indicate that acute doses of KBr as high as 150 mg/kg are required to hamper
memory function in ORT. However, cognitive impairment occured with lower doses of
KBr when the duration of treatment is extended.
PMID- 28515771
TI - Erratum: The structural model of pain, cognitive strategies, and negative
emotions in functional gastrointestinal disorders.
AB - [This corrects the article on p. 107 in vol. 21, PMID: 28250784.].
PMID- 28515772
TI - Retrospective voting and party support at elections: credit and blame for
government and opposition.
AB - Retrospective voting is arguably one of the most important mechanisms of
representative democracy, and whether or not the public holds the government
accountable for its policy performance has been extensively studied. In this
paper, we test whether retrospective voting extends to parties in the opposition,
that is whether and how parties' past performance evaluations affect their vote,
regardless of whether they were in government or in opposition. Taking advantage
of a rich set of questions embedded in a representative German national elections
panel, we update our knowledge on the retrospective voting mechanism by modeling
retrospective voting at the party level. The findings indicate that the incumbent
status is not the only criterion for retrospective voting, ultimately suggesting
that both government and opposition parties can expect credit and blame for their
conduct and this should provide some impetus for responsive performance of all
parties.
PMID- 28515770
TI - High level expression of recombinant human growth hormone in Escherichia coli:
crucial role of translation initiation region.
AB - For high-throughput production of recombinant protein in Escherichia coli (E.
coli), besides important parameters such as efficient vector with strong promoter
and compatible host, other important issues including codon usage, rare codons,
and GC content specially at N-terminal region should be considered. In the
current study, the effect of decreasing the percentage of GC nucleotides and
optimizing codon usage at N-terminal region of human growth hormone (hGH) cDNA on
the level of its expression in E. coli were investigated. Mutation in cDNA of hGH
was performed through site-directed mutagenesis using PCR. Then, the mutant genes
were amplified and cloned into the expression vector, pET-28a. The new constructs
were transformed into the BL21(DE3) strain of E. coli and chemically induced for
hGH expression. At the final stage, expressed proteins were analyzed by sodium
dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), scanning gel
densitometry, and western blot. SDS-PAGE scanning gel densitometry assay and
western blot analysis revealed higher expression level of hGH by using the two
new expressions constructs (mutant genes vectors with decreasing GC content and
optimized-codon usage at N-terminal of cDNA) in comparison with wild gene
expression vector. Obtained results demonstrated that decreasing the GC
nucleotide content and optimization of codon usage at N-terminal of the hGH cDNA
could significantly enhance the expression of the target protein in E. coli. Our
results highlight the important role of both 5' region of the heterologous genes
in terms of codon usage and also GC content on non-host protein expression in E.
coli.
PMID- 28515774
TI - Complexity and algorithms for copy-number evolution problems.
AB - BACKGROUND: Cancer is an evolutionary process characterized by the accumulation
of somatic mutations in a population of cells that form a tumor. One frequent
type of mutations is copy number aberrations, which alter the number of copies of
genomic regions. The number of copies of each position along a chromosome
constitutes the chromosome's copy-number profile. Understanding how such profiles
evolve in cancer can assist in both diagnosis and prognosis. RESULTS: We model
the evolution of a tumor by segmental deletions and amplifications, and gauge
distance from profile [Formula: see text] to [Formula: see text] by the minimum
number of events needed to transform [Formula: see text] into [Formula: see
text]. Given two profiles, our first problem aims to find a parental profile that
minimizes the sum of distances to its children. Given k profiles, the second,
more general problem, seeks a phylogenetic tree, whose k leaves are labeled by
the k given profiles and whose internal vertices are labeled by ancestral
profiles such that the sum of edge distances is minimum. CONCLUSIONS: For the
former problem we give a pseudo-polynomial dynamic programming algorithm that is
linear in the profile length, and an integer linear program formulation. For the
latter problem we show it is NP-hard and give an integer linear program
formulation that scales to practical problem instance sizes. We assess the
efficiency and quality of our algorithms on simulated instances. AVAILABILITY:
https://github.com/raphael-group/CNT-ILP.
PMID- 28515775
TI - Retrospective mortality among refugees from the Central African Republic arriving
in Chad, 2014.
AB - BACKGROUND: The Central African Republic has known long periods of instability.
In 2014, following the fall of an interim government installed by the Seleka
coalition, a series of violent reprisals occurred. These events were largely
directed at the country's Muslim minority and led to a massive displacement of
the population. In 2014, we sought to document the retrospective mortality among
refugees arriving from the CAR into Chad by conducting a series of surveys.
METHODS: The Sido camp was surveyed exhaustively in March-April 2014 and a
systematic sampling strategy was used in the Gore camp in October 2014. The
survey recall period began November 1, 2013, just before the major anti-Balaka
offensive. Heads of households were asked to describe their household composition
at the beginning o f and throughout the recall period. For household members
reported as dying, further information about the date and circumstances of death
was obtained. RESULTS: In Sido, 3449 households containing 25 353 individuals
were interviewed. A total of 2599 deaths were reported, corresponding to a crude
mortality rate of 6.0/10000 persons/day, and 8% of the population present at the
beginning of the recall period died. Most (82.4%) deaths occurred among males,
most deaths occurred in December 2013 and January 2014, and 92% were due to
violence in the CAR. In Gore, 1383 households containing 8614 individuals were
interviewed. A total of 1203 deaths were reported, corresponding to a crude
mortality rate of 3.7/10000 persons/day [95%CI 3.5-3.9], and 12% of the
population present at the beginning of the recall period died. Most (77.1%)
deaths occurred among males. As in Sido, most deaths occurred in December 2013
and January 2014, and 86% of all deaths were due to violence in the CAR.
CONCLUSIONS: The results of these two surveys describe a part of the toll of the
violent events of December 2013 and January 2014 in the Central African Republic.
PMID- 28515773
TI - Building a multipurpose insertional mutant library for forward and reverse
genetics in Chlamydomonas.
AB - BACKGROUND: The unicellular green alga, Chlamydomonas reinhardtii, is a classic
model for studying flagella and biofuel. However, precise gene editing, such as
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR
associated protein (Cas9) system, is not widely used in this organism. Screening
of random insertional mutant libraries by polymerase chain reaction provides an
alternate strategy to obtain null mutants of individual gene. But building,
screening, and maintaining such a library was time-consuming and expensive.
RESULTS: By selecting a suitable parental strain, keeping individual mutants
using the agar plate, and designing an insertion cassette-specific primer for
library screening, we successfully generated and maintained ~150,000 insertional
mutants of Chlamydomonas, which was used for both reverse and forward genetics
analysis. We obtained 26 individual mutants corresponding to 20 genes and
identified 967 motility-defect mutants including 10 mutants with defective
accumulation of intraflagellar transport complex at the basal body. We also
obtained 929 mutants defective in oil droplet assembly after nitrogen
deprivation. Furthermore, a new insertion cassette with splicing donor sequences
at both ends was also constructed, which increased the efficiency of gene
interruption. CONCLUSION: In summary, this library provides a multifunctional
platform both for obtaining mutants of interested genes and for screening of
mutants with specific phenotype.
PMID- 28515776
TI - Hormonally active phytochemicals and vertebrate evolution.
AB - Living plants produce a diversity of chemicals that share structural and
functional properties with vertebrate hormones. Wildlife species interact with
these chemicals either through consumption of plant materials or aquatic
exposure. Accumulating evidence shows that exposure to these hormonally active
phytochemicals (HAPs) often has consequences for behavior, physiology, and
fecundity. These fitness effects suggest there is potential for an evolutionary
response by vertebrates to HAPs. Here, we explore the toxicological HAP
vertebrate relationship in an evolutionary framework and discuss the potential
for vertebrates to adapt to or even co-opt the effects of plant-derived chemicals
that influence fitness. We lay out several hypotheses about HAPs and provide a
path forward to test whether plant-derived chemicals influence vertebrate
reproduction and evolution. Studies of phytochemicals with direct impacts on
vertebrate reproduction provide an obvious and compelling system for studying
evolutionary toxicology. Furthermore, an understanding of whether animal
populations evolve in response to HAPs could provide insightful context for the
study of rapid evolution and how animals cope with chemical agents in the
environment.
PMID- 28515778
TI - Evolution of movement rate increases the effectiveness of marine reserves for the
conservation of pelagic fishes.
AB - Current debates about the efficacy of no-take marine reserves (MR) in protecting
large pelagic fish such as tuna and sharks have usually not considered the
evolutionary dimension of this issue, which emerges because the propensity to
swim away from a given place, like any other biological trait, will probably vary
in a heritable fashion among individuals. Here, based on spatially explicit
simulations, we investigated whether selection to remain in MRs to avoid higher
fishing mortality can lead to the evolution of more philopatric fish. Our
simulations, which covered a range of life histories among tuna species (skipjack
tuna vs. Atlantic bluefin tuna) and shark species (great white sharks vs. spiny
dogfish), suggested that MRs were most effective at maintaining viable population
sizes when movement distances were lowest. Decreased movement rate evolved
following the establishment of marine reserves, and this evolution occurred more
rapidly with higher fishing pressure. Evolutionary reductions in movement rate
led to increases in within-reserve population sizes over the course of the 50
years following MR establishment, although this varied among life histories, with
skipjack responding fastest and great white sharks slowest. Our results suggest
the evolution of decreased movement can augment the efficacy of marine reserves,
especially for species, such as skipjack tuna, with relatively short generation
times. Even when movement rates did not evolve substantially over 50 years (e.g.,
given long generation times or little heritable variation), marine reserves were
an effective tool for the conservation of fish populations when mean movement
rates were low or MRs were large.
PMID- 28515777
TI - Experimental evolution to increase the efficacy of the entomopathogenic fungus
Beauveria bassiana against malaria mosquitoes: Effects on mycelial growth and
virulence.
AB - Entomopathogenic fungi such as Beauveria bassiana are currently considered as a
potential control agent for malaria mosquitoes. The success of such strategies
depends among others on the efficacy of the fungus to kill its hosts. As B.
bassiana can use various resources for growth and reproduction, increasing the
dependency on mosquitoes as a nutritional source may be instrumental for reaching
this goal. Passage of entomopathogenic fungi through an insect host has been
shown to increase its virulence. We evaluated the virulence, fungal outgrowth,
mycelial growth rate, and sporulation rate of two B. bassiana isolates (Bb1520
and Bb8028) that underwent 10 consecutive selection cycles through malaria
mosquitoes (Anopheles coluzzii) using an experimental evolution approach. This
cycling resulted in an altered capacity of evolved B. Bassiana lineages to grow
on different substrates while maintaining the ability to kill insects. Notably,
however, there were no significant changes in virulence or speed of outgrowth
when comparing the evolved lineages against their unevolved ancestors. These
results suggest that fungal growth and sporulation evolved through successive and
exclusive use of an insect host as a nutritional resource. We discuss the results
in light of biocontrol and provide suggestions to increase fungal virulence.
PMID- 28515779
TI - Higher resource level promotes virulence in an environmentally transmitted
bacterial fish pathogen.
AB - Diseases have become a primary constraint to sustainable aquaculture, but
remarkably little attention has been paid to a broad class of pathogens: the
opportunists. Opportunists often persist in the environment outside the host, and
their pathogenic features are influenced by changes in the environment. To test
how environmental nutrient levels influence virulence, we used strains of
Flavobacterium columnare, an environmentally transmitted fish pathogen, to infect
rainbow trout and zebra fish in two different nutrient concentrations. To
separate the effects of dose and nutrients, we used three infective doses and
studied the growth of bacteria in vitro. High nutrient concentration promoted
both the virulence and the outside-host growth of the pathogen, most notably in a
low-virulence strain. The increase in virulence could not be exhaustively
explained by the increased dose under higher nutrient supply, suggesting
virulence factor activation. In aquaculture settings, accumulation of organic
material in rearing units can locally increase water nutrient concentration and
therefore increase disease risk as a response to elevated bacterial density and
virulence factor activation. Our results highlight the role of increased
nutrients in outside-host environment as a selective agent for higher virulence
and faster evolutionary rate in opportunistic pathogens.
PMID- 28515780
TI - Evolution and the duration of a doomed population.
AB - Many populations are doomed to extinction, but little is known about how
evolution contributes to their longevity. We address this by modeling an asexual
population consisting of genotypes whose abundances change independently
according to a system of continuous branching diffusions. Each genotype is
characterized by its initial abundance, growth rate, and reproductive variance.
The latter two components determine the genotype's "risk function" which
describes its per capita probability of extinction at any time. We derive the
probability distribution of extinction times for a polymorphic population, which
can be expressed in terms of genotypic risk functions. We use this to explore how
spontaneous mutation, abrupt environmental change, or population supplementation
and removal affect the time to extinction. Results suggest that evolution based
on new mutations does little to alter the time to extinction. Abrupt
environmental changes that affect all genotypes can have more substantial impact,
but, curiously, a beneficial change does more to extend the lifetime of thriving
than threatened populations of the same initial abundance. Our results can be
used to design policies that meet specific conservation goals or management
strategies that speed the elimination of agricultural pests or human pathogens.
PMID- 28515781
TI - Evolutionary restoration potential evaluated through the use of a trait-linked
genetic marker.
AB - Human-driven evolution can impact the ecological role and conservation value of
impacted populations. Most evolutionary restoration approaches focus on
manipulating gene flow, but an alternative approach is to manipulate the
selection regime to restore historical or desired trait values. Here we examined
the potential utility of this approach to restore anadromous migratory behavior
in coastal California steelhead trout (Oncorhynchus mykiss) populations. We
evaluated the effects of natural and anthropogenic environmental variables on the
observed frequency of alleles at a genomic marker tightly associated with
migratory behavior across 39 steelhead populations from across California, USA.
We then modeled the potential for evolutionary restoration at sites that have
been impacted by anthropogenic barriers. We found that complete barriers such as
dams are associated with major reductions in the frequency of anadromy-associated
alleles. The removal of dams is therefore expected to restore anadromy
significantly. Interestingly, accumulations of large numbers of partial barriers
(passable under at least some flow conditions) were also associated with
significant reductions in migratory allele frequencies. Restoration involving the
removal of partial barriers could be evaluated alongside dam removal and fishway
construction as a cost-effective tool to restore anadromous fish migrations.
Results encourage broader consideration of in situ evolution during the
development of habitat restoration projects.
PMID- 28515783
TI - Trans-generational plasticity in response to immune challenge is constrained by
heat stress.
AB - Trans-generational plasticity (TGP) is the adjustment of phenotypes to changing
habitat conditions that persist longer than the individual lifetime. Fitness
benefits (adaptive TGP) are expected upon matching parent-offspring environments.
In a global change scenario, several performance-related environmental factors
are changing simultaneously. This lowers the predictability of offspring
environmental conditions, potentially hampering the benefits of TGP. For the
first time, we here explore how the combination of an abiotic and a biotic
environmental factor in the parental generation plays out as trans-generational
effect in the offspring. We fully reciprocally exposed the parental generation of
the pipefish Syngnathus typhle to an immune challenge and elevated temperatures
simulating a naturally occurring heatwave. Upon mating and male pregnancy,
offspring were kept in ambient or elevated temperature regimes combined with a
heat-killed bacterial epitope treatment. Differential gene expression (immune
genes and DNA- and histone-modification genes) suggests that the combined change
of an abiotic and a biotic factor in the parental generation had interactive
effects on offspring performance, the temperature effect dominated over the
immune challenge impact. The benefits of certain parental environmental
conditions on offspring performance did not sum up when abiotic and biotic
factors were changed simultaneously supporting that available resources that can
be allocated to phenotypic trans-generational effects are limited. Temperature is
the master regulator of trans-generational phenotypic plasticity, which
potentially implies a conflict in the allocation of resources towards several
environmental factors. This asks for a reassessment of TGP as a short-term option
to buffer environmental variation in the light of climate change.
PMID- 28515782
TI - Ecotypic differentiation under farmers' selection: Molecular insights into the
domestication of Pachyrhizus Rich. ex DC. (Fabaceae) in the Peruvian Andes.
AB - Understanding the distribution of crop genetic diversity in relation to
environmental factors can give insights into the eco-evolutionary processes
involved in plant domestication. Yam beans (Pachyrhizus Rich. ex DC.) are
leguminous crops native to South and Central America that are grown for their
tuberous roots but are seed-propagated. Using a landscape genetic approach, we
examined correlations between environmental factors and phylogeographic patterns
of genetic diversity in Pachyrhizus landrace populations. Molecular analyses
based on chloroplast DNA sequencing and a new set of nuclear microsatellite
markers revealed two distinct lineages, with strong genetic differentiation
between Andean landraces (lineage A) and Amazonian landraces (lineage B). The
comparison of different evolutionary scenarios for the diversification history of
yam beans in the Andes using approximate Bayesian computation suggests that
Pachyrhizus ahipa and Pachyrhizus tuberosus share a progenitor-derivative
relationship, with environmental factors playing an important role in driving
selection for divergent ecotypes. The new molecular data call for a revision of
the taxonomy of Pachyrhizus but are congruent with paleoclimatic and
archeological evidence, and suggest that selection for determinate growth was
part of ecophysiological adaptations associated with the diversification of the
P. tuberosus-P. ahipa complex during the Mid-Holocene.
PMID- 28515784
TI - Improving Saccharomyces cerevisiae ethanol production and tolerance via RNA
polymerase II subunit Rpb7.
AB - BACKGROUND: Classical strain engineering methods often have limitations in
altering multigenetic cellular phenotypes. Here we try to improve Saccharomyces
cerevisiae ethanol tolerance and productivity by reprogramming its transcription
profile through rewiring its key transcription component RNA polymerase II (RNAP
II), which plays a central role in synthesizing mRNAs. This is the first report
on using directed evolution method to engineer RNAP II to alter S. cerevisiae
strain phenotypes. RESULTS: Error-prone PCR was employed to engineer the subunit
Rpb7 of RNAP II to improve yeast ethanol tolerance and production. Based on
previous studies and the presumption that improved ethanol resistance would lead
to enhanced ethanol production, we first isolated variant M1 with much improved
resistance towards 8 and 10% ethanol. The ethanol titers of M1 was ~122 g/L
(96.58% of the theoretical yield) under laboratory very high gravity (VHG)
fermentation, 40% increase as compared to the control. DNA microarray assay
showed that 369 genes had differential expression in M1 after 12 h VHG
fermentation, which are involved in glycolysis, alcoholic fermentation, oxidative
stress response, etc. CONCLUSIONS: This is the first study to demonstrate the
possibility of engineering eukaryotic RNAP to alter global transcription profile
and improve strain phenotypes. Targeting subunit Rpb7 of RNAP II was able to
bring differential expression in hundreds of genes in S. cerevisiae, which
finally led to improvement in yeast ethanol tolerance and production.
PMID- 28515786
TI - Evaluation of biomass quality in short-rotation bamboo (Phyllostachys pubescens)
for bioenergy products.
AB - BACKGROUND: In order to improve the availability of biomass, the concept of
growing high yield biomass with short rotations and intensive culture has been
introduced. Bamboo has become a feedstock of potential interest for future energy
production due to its high productivity and short rotation time. The growth age
of biomass is an important factor affecting the efficiency of bioconversion and
pretreatment for bioenergy production. In this regard, more information is
required on the morphology and chemical composition of bamboo for short-rotation
biomass production. In this study, we used a compositional assay to compare a
bamboo of two different growth ages. RESULTS: Bamboo of two different ages showed
characteristics patterns of morphology, chemical composition, and bioconversion.
In young-age (2-month-old) bamboo, the pattern of tissue organization was similar
to that of old-age (3-year-old) bamboo, indicating that the former had reached
its full height. There were significant differences between young-age and old-age
bamboo in terms of chemical composition. The glucose contents in old-age bamboo
did not differ significantly among its internodes. For young-age bamboo, the
lignin contents were 14.6-18.3%, whereas those of old-age bamboo were
considerably higher, ranging from 25.4 to 27.1% with increasing syringyl-to
guaiacyl ratio. The yield of total sugars following enzymatic hydrolysis of young
age bamboo was approximately eight times. However, following hydrogen peroxide
acetic acid pretreatment, the results of separate hydrolysis and fermentation and
simultaneous saccharification and fermentation did not differ significantly
between young- and old-age bamboo. However, ethanol production was higher in 2
month old than in 3-year old from initial raw biomass. CONCLUSION: Our data show
that the production of total sugar from raw material was high in young bamboo
with low lignin content. With respect to short-rotation biomass, bamboo culm
harvested after termination of height growth is more appropriate for use as a
biomass resource to achieve a high yield for bioconversion process.
PMID- 28515785
TI - Recombinant expression of thermostable processive MtEG5 endoglucanase and its
synergism with MtLPMO from Myceliophthora thermophila during the hydrolysis of
lignocellulosic substrates.
AB - BACKGROUND: Filamentous fungi are among the most powerful cellulolytic organisms
in terrestrial ecosystems. To perform the degradation of lignocellulosic
substrates, these microorganisms employ both hydrolytic and oxidative mechanisms
that involve the secretion and synergism of a wide variety of enzymes.
Interactions between these enzymes occur on the level of saccharification, i.e.,
the release of neutral and oxidized products, but sometimes also reflected in the
substrate liquefaction. Although the synergism regarding the yield of neutral
sugars has been extensively studied, further studies should focus on the oxidized
sugars, as well as the effect of enzyme combinations on the viscosity properties
of the substrates. RESULTS: In the present study, the heterologous expression of
an endoglucanase (EG) and its combined activity together with a lytic
polysaccharide monooxygenase (LPMO), both from the thermophilic fungus
Myceliophthora thermophila, are described. The EG gene, belonging to the
glycoside hydrolase family 5, was functionally expressed in the methylotrophic
yeast Pichia pastoris. The produced MtEG5A (75 kDa) featured remarkable thermal
stability and showed high specific activity on microcrystalline cellulose
compared to CMC, which is indicative of its processivity properties. The enzyme
was capable of releasing high amounts of cellobiose from wheat straw, birch, and
spruce biomass. Addition of MtLPMO9 together with MtEG5A showed enhanced
enzymatic hydrolysis yields against regenerated amorphous cellulose (PASC) by
improving the release not only of the neutral but also of the oxidized sugars.
Assessment of activity of MtEG5A on the reduction of viscosity of PASC and
pretreated wheat straw using dynamic viscosity measurements revealed that the
enzyme is able to perform liquefaction of the model substrate and the natural
lignocellulosic material, while when added together with MtLPMO9, no further
synergistic effect was observed. CONCLUSIONS: The endoglucanase MtEG5A from the
thermophilic fungus M. thermophila exhibited excellent properties that render it
a suitable candidate for use in biotechnological applications. Its strong
synergism with LPMO was reflected in sugars release, but not in substrate
viscosity reduction. Based on the level of oxidative sugar formation, this is the
first indication of synergy between LPMO and EG reported.
PMID- 28515789
TI - Towards Miscanthus combustion quality improvement: the role of flowering and
senescence.
AB - In commercially grown Miscanthus * giganteus, despite imposing a yield penalty,
postwinter harvests improve quality criteria for thermal conversion and crop
sustainability through remobilization of nutrients to the underground rhizome. We
examined 16 Miscanthus genotypes with different flowering and senescence times
for variation in N, P, K, moisture, ash, Cl and Si contents, hypothesizing that
early flowering and senescence could result in improved biomass quality and/or
enable an earlier harvest of biomass (in autumn at peak yield). Ideal crop
characteristics at harvest are low N and P to reduce future fertilizer inputs,
low K and Cl to reduce corrosion in boilers, low moisture to reduce spoilage and
transportation costs, and low Si and ash to reduce slagging and consequent
operational downtime. Stems and leaves were harvested during summer, autumn and
then the following spring after overwinter ripening. In spring, stem contents of
N were 30-60 mg kg-1, P were 203-1132 mg kg-1, K were 290-4098 mg kg-1, Cl were
10-23 mg kg-1 and moisture were 12-38%. Notably, late senescence resulted in
increased N, P, K, Cl, moisture and ash contents, and should therefore be avoided
for thermochemical conversion. Flowering and senescence led to overall improved
combustion quality, where flowered genotypes tended towards lower P, K, Cl and
moisture contents; marginally less, or similar, N, Si and ash contents; and a
similar higher heating value, compared to those that had not flowered. Such
genotypes could potentially be harvested in the autumn. However, one genotype
that did not flower in our trial exhibited sufficiently low N and K content in
autumn to meet the EN plus wood pellet standards for those traits, and some of
the lowest P, moisture and ash contents in our trial, and is thus a target for
future research and breeding.
PMID- 28515787
TI - A computational approach for the functional classification of the epigenome.
AB - BACKGROUND: In the last decade, advanced functional genomics approaches and deep
sequencing have allowed large-scale mapping of histone modifications and other
epigenetic marks, highlighting functional relationships between chromatin
organization and genome function. Here, we propose a novel approach to explore
functional interactions between different epigenetic modifications and extract
combinatorial profiles that can be used to annotate the chromatin in a finite
number of functional classes. Our method is based on non-negative matrix
factorization (NMF), an unsupervised learning technique originally employed to
decompose high-dimensional data in a reduced number of meaningful patterns. We
applied the NMF algorithm to a set of different epigenetic marks, consisting of
ChIP-seq assays for multiple histone modifications, Pol II binding and chromatin
accessibility assays from human H1 cells. RESULTS: We identified a number of
chromatin profiles that contain functional information and are biologically
interpretable. We also observe that epigenetic profiles are characterized by
specific genomic contexts and show significant association with distinct genomic
features. Moreover, analysis of RNA-seq data reveals that distinct chromatin
signatures correlate with the level of gene expression. CONCLUSIONS: Overall, our
study highlights the utility of NMF in studying functional relationships between
different epigenetic modifications and may provide new biological insights for
the interpretation of the chromatin dynamics.
PMID- 28515791
TI - Vildagliptin has the same safety profile as a sulfonylurea on bone metabolism and
bone mineral density in post-menopausal women with type 2 diabetes: a randomized
controlled trial.
AB - BACKGROUND: Several antidiabetic therapies affect bone metabolism. Sulfonylureas
have the lowest impact on bone among oral antidiabetics. The objective of this
study is to compare the effects of vildagliptin and gliclazide modified release
(MR) on bone turnover markers (BTMs) and bone mineral density (BMD) in
postmenopausal women with uncontrolled type 2 diabetes (T2D). METHODS: Forty-two
postmenopausal women with uncontrolled T2D were randomly allocated into
vildagliptin or gliclazide MR (control) groups. The primary endpoint was the
change in the BTMs in months 6 and 12 compared with the baseline. The secondary
endpoint was the variation in the BMD, which was assessed via dual-energy X-ray
absorptiometry at the lumbar spine, femoral neck and total hip at baseline and
month 12. RESULTS: After a 12-month treatment, the BTM serum carboxy-terminal
telopeptide of type 1 collagen increased 0.001 +/- 0.153 ng/mL in the
vildagliptin group versus 0.008 +/- 0.060 ng/mL in the gliclazide MR group (p =
0.858). The serum osteocalcin, serum amino-terminal propeptide of procollagen
type I and urinary amino-terminal telopeptide of type 1 collagen remained stable
in both groups, and there was no statistically significant difference between the
effect of vildagliptin and gliclazide MR on these variables. The lumbar spine BMD
did not change in the vildagliptin or gliclazide MR groups after a 12-month
treatment (0.000 +/- 0.025 g/cm2 versus -0.008 +/- 0.036, respectively, p =
0.434). Furthermore, there was a similar lack of change in the femoral neck and
total hip BMD values in both treatments. CONCLUSIONS: Bone turnover markers and
BMD remained unchanged after a 12-month treatment in both groups, which suggests
that vildagliptin has the same safety profile as gliclazide MR on bone
metabolism. Trial Registration ClinicalTrials.gov number NCT01679899.
PMID- 28515790
TI - Comparative genomic analysis reveals genetic features related to the virulence of
Bacillus cereus FORC_013.
AB - BACKGROUND: Bacillus cereus is well known as a gastrointestinal pathogen that
causes food-borne illness. In the present study, we sequenced the complete genome
of B. cereus FORC_013 isolated from fried eel in South Korea. To extend our
understanding of the genomic characteristics of FORC_013, we conducted a
comparative analysis with the published genomes of other B. cereus strains.
RESULTS: We fully assembled the single circular chromosome (5,418,913 bp) and one
plasmid (259,749 bp); 5511 open reading frames (ORFs) and 283 ORFs were predicted
for the chromosome and plasmid, respectively. Moreover, we detected that the
enterotoxin (NHE, HBL, CytK) induces food-borne illness with diarrheal symptom,
and that the pleiotropic regulator, along with other virulence factors, plays a
role in surviving and biofilm formation. Through comparative analysis using the
complete genome sequence of B. cereus FORC_013, we identified both positively
selected genes related to virulence regulation and 224 strain-specific genes of
FORC_013. CONCLUSIONS: Through genome analysis of B. cereus FORC_013, we
identified multiple virulence factors that may contribute to pathogenicity. These
results will provide insight into further studies regarding B. cereus
pathogenesis mechanism at the genomic level.
PMID- 28515788
TI - Genomic imprinting does not reduce the dosage of UBE3A in neurons.
AB - BACKGROUND: The ubiquitin protein E3A ligase gene (UBE3A) gene is imprinted with
maternal-specific expression in neurons and biallelically expressed in all other
cell types. Both loss-of-function and gain-of-function mutations affecting the
dosage of UBE3A are associated with several neurodevelopmental syndromes and
psychological conditions, suggesting that UBE3A is dosage-sensitive in the brain.
The observation that loss of imprinting increases the dosage of UBE3A in brain
further suggests that inactivation of the paternal UBE3A allele evolved as a
dosage-regulating mechanism. To test this hypothesis, we examined UBE3A
transcript and protein levels among cells, tissues, and species with different
imprinting states of UBE3A. RESULTS: Overall, we found no correlation between the
imprinting status and dosage of UBE3A. Importantly, we found that maternal Ube3a
protein levels increase in step with decreasing paternal Ube3a protein levels
during neurogenesis in mouse, fully compensating for loss of expression of the
paternal Ube3a allele in neurons. CONCLUSIONS: Based on our findings, we propose
that imprinting of UBE3A does not function to reduce the dosage of UBE3A in
neurons but rather to regulate some other, as yet unknown, aspect of gene
expression or protein function.
PMID- 28515794
TI - Influence of a home-based exercise program on the urine pH in elderly female
subjects: a secondary analysis of a randomized controlled trial.
AB - BACKGROUND: A low urine pH is a characteristic metabolic feature of metabolic
syndrome and type 2 diabetes. The purpose of the current study was to investigate
the effects of a 12-week home-based bench step exercise on the urine pH status of
elderly female subjects. METHODS: The current study is a secondary analysis of a
randomized controlled trial (RCT) in which 59 postmenopausal female subjects were
randomized to either the exercise group (n = 29) or the control group (n = 30).
The subjects in the exercise group were instructed to perform home-based
exercises using a bench step at the anaerobic threshold (AT), with a goal of
performing >=140 min/week at home for 12 weeks. The subjects in the control group
were instructed to not change their normal lifestyle. Urine was collected after
overnight fasting, and the urine pH was measured using a urinary test strip. The
inter-group-differences at baseline and the pre-post changes within groups were
assessed using the Mann-Whitney U test and Wilcoxon's signed-rank test,
respectively. Additionally, the difference in the post-intervention urine pH
levels of the two groups, adjusted for the pre-intervention values (the estimated
effect size) and the precision (95% confidence intervals) were investigated using
an analysis of covariance. RESULTS: The pre-post comparison of the urine pH data
using Wilcoxon's signed-rank test showed a significant increase in the urine pH
levels of the exercise group (p < 0.05); there was no significant change in the
urine pH levels of the control group. However, the estimated effect size (0.15)
was small and the confidence interval straddled 0 (-0.25-0.55). CONCLUSIONS:
Based on the results of the current secondary analysis of an RCT, we could not
clearly conclude that exercise has a beneficial effect on the urine pH. Further
well-designed RCTs should be conducted to determine whether aerobic exercise is
truly able to ameliorate urine acidification. TRIAL REGISTRATION: The study was
retrospectively registered in the University Hospital Medical Information Network
(UMIN) as "Effect of step exercise on aerobic fitness and progression of
atherosclerosis in the elderly" under the registration number UMIN 000026743 (the
date of registration: March 28, 2017).
PMID- 28515792
TI - Mesenchymal stem cell therapy in type 2 diabetes mellitus.
AB - Type 2 diabetes mellitus (T2DM), which is characterized by the combination of
relative insulin deficiency and insulin resistance, cannot be reversed with
existing therapeutic strategies. Transplantation of insulin-producing cells
(IPCs) was once thought to be the most promising strategy for treating diabetes,
but the pace from the laboratory to clinical application has been obstructed due
to its drawbacks. Mesenchymal stem cells (MSCs) harbor differentiation potential,
immunosuppressive properties, and anti-inflammatory effects, and they are
considered an ideal candidate cell type for treatment of DM. MSC-related research
has demonstrated exciting therapeutic effects in glycemic control both in vivo
and in vitro, and these results now have been translated into clinical practice.
However, some critical potential problems have emerged from current clinical
trials. Multi-center, large-scale, double-blind, and placebo-controlled studies
with strict supervision are required before MSC transplantation can become a
routine therapeutic approach for T2DM. We briefly review the molecular mechanism
of MSC treatment for T2DM as well as the merits and drawbacks identified in
current clinical trials.
PMID- 28515793
TI - Does the diurnal cycle of cortisol explain the relationship between physical
performance and cognitive function in older adults?
AB - BACKGROUND: Regular physical activity is a promising strategy to treat and
prevent cognitive decline. The mechanisms that mediate these benefits are not
fully clear but physical activity is thought to attenuate the harmful effects of
chronic psychological stress and hypercortisolism on cognition. However, the
circadian pattern of cortisol secretion is complex and it is not known which
aspects are most closely associated with increased cognitive function and better
physical performance. This is the first study to simultaneously measure cognitive
function, the diurnal cycle of salivary cortisol and physical performance in
older adults, without cognitive impairment (n = 30) and with amnestic Mild
Cognitive Impairment (aMCI) (n = 30). RESULTS: Regression analysis showed that
better cognitive function was associated with better physical performance. A
greater variance in cortisol levels across the day from morning to evening was
associated with better cognitive function and physical performance. CONCLUSIONS:
The results support the idea that a more dynamic cortisol secretion pattern is
associated with better cognitive function and physical performance even in the
presence of cognitive impairment, but our results could not confirm a mediating
role in this relationship.
PMID- 28515795
TI - A Theoretical Investigation on CO Oxidation by Single-Atom Catalysts M1/gamma
Al2O3 (M=Pd, Fe, Co, and Ni).
AB - Single-atom catalysts have attracted much interest recently because of their
excellent stability, high catalytic activity, and remarkable atom efficiency.
Inspired by the recent experimental discovery of a highly efficient single-atom
catalyst Pd1/gamma-Al2O3, we conducted a comprehensive DFT study on geometries,
stabilities and CO oxidation catalytic activities of M1/gamma-Al2O3 (M=Pd, Fe,
Co, and Ni) by using slab-model. One of the most important results here is that
Ni1/Al2O3 catalyst exhibits higher activity in CO oxidation than Pd1/Al2O3. The
CO oxidation occurs through the Mars van Krevelen mechanism, the rate-determining
step of which is the generation of CO2 from CO through abstraction of surface
oxygen. The projected density of states (PDOS) of 2p orbitals of the surface O,
the structure of CO-adsorbed surface, charge polarization of CO and charge
transfer from CO to surface are important factors for these catalysts. Although
the binding energies of Fe and Co with Al2O3 are very large, those of Pd and Ni
are small, indicating that the neighboring O atom is not strongly bound to Pd and
Ni, which leads to an enhancement of the reactivity of the O atom toward CO. The
metal oxidation state is suggested to be one of the crucial factors for the
observed catalytic activity.
PMID- 28515799
TI - Implementing Mindfulness in the Mainstream: Making the Path by Walking It.
AB - There is expanding interest in mindfulness-based programs (MBPs) within the
mainstream. While there are research gaps, there is empirical evidence for these
developments. Implementing new evidence into practice is always complex and
difficult. Particular complexities and tensions arise when implementing MBPs in
the mainstream. MBPs are emerging out of the confluence of different
epistemologies-contemplative teaching and practice, and contemporary Western
empiricism and culture. In the process of navigating implementation and
integrity, and developing a professional practice context for this emerging
field, the diverse influences within this confluence need careful attention and
thought. Both contemplative practices, and mainstream institutions and
professional practice have well-developed ethical understandings and integrity.
MBPs aim to balance fidelity to both. This includes the need to further develop
skillful expressions of the underpinning theoretical and philosophical framework
for MBPs; to sensitively work with the boundary between mainstream and religious
mindfulness; to develop organizational structures which support governance and
collaboration; to investigate teacher training, supervision models, and teaching
competence; to develop consensus on the ethical frameworks on which mainstream
MBPs rests; and to build understanding and work skillfully with barriers to
access to MBPs. It is equally important to attend to how these developments are
conducted. This includes the need to align with values integral to mindfulness,
and to hold longer-term intentions and directions, while taking small, deliberate
steps in each moment. The MBP field needs to establish itself as a new
professional field and stand on its own integrity.
PMID- 28515796
TI - Genetic heterogeneity of patients with suspected Silver-Russell syndrome: genome
wide copy number analysis in 82 patients without imprinting defects.
AB - BACKGROUND: Silver-Russell syndrome (SRS) is a rare congenital disorder
characterized by pre- and postnatal growth failure and dysmorphic features.
Recently, pathogenic copy number variations (PCNVs) and imprinting defects other
than hypomethylation of the H19-differentially methylated region (DMR) and
maternal uniparental disomy chromosome 7 have been reported in patients with the
SRS phenotype. This study aimed to clarify the frequency and clinical features of
patients with SRS phenotype caused by PCNVs. METHODS: We performed array
comparative genomic hybridization analysis using a catalog array for 54 patients
satisfying the Netchine-Harbison clinical scoring system (NH-CSS) (SRS
compatible) and for 28 patients presenting with three NH-CSS items together with
triangular face and/or fifth finger clinodactyly and/or brachydactyly (SRS-like)
without abnormal methylation levels of 9 DMRs related to known imprinting
disorders. We then investigated the clinical features of patients with PCNVs.
RESULTS: Three of the 54 SRS-compatible patients (5.6%) and 2 of the 28 SRS-like
patients (7.1%) had PCNVs. We detected 3.5 Mb deletion in 4p16.3, mosaic trisomy
18, and 3.77-4.00 Mb deletion in 19q13.11-12 in SRS-compatible patients, and 1.41
1.97 Mb deletion in 7q11.23 in both SRS-like patients. Congenital heart diseases
(CHDs) were identified in two patients and moderate to severe global
developmental delay was observed in four patients. CONCLUSIONS: Of the patients
in our study, 5.6% of SRS-compatible and 7.1% of SRS-like patients had PCNVs. All
PCNVs have been previously reported for genetic causes of contiguous deletion
syndromes or mosaic trisomy 18. Our study suggests patients with PCNVs, who have
a phenotype resembling SRS, show a high tendency towards CHDs and/or apparent
developmental delay.
PMID- 28515800
TI - Dimensions of Mindfulness and Their Relations with Psychological Well-Being and
Neuroticism.
AB - In this study we examined whether differences in the habitual use of mindfulness
skills were associated with specific well-being and neuroticism aspects. Two
hundred eleven volunteers aged 21-84 years completed measures of mindfulness,
neuroticism, psychological well-being (PWB), and subjective well-being (SWB).
Describing, observing, and acting with awareness (i.e., the mindfulness "what"
skills) were positively correlated with personal growth, purpose in life, and
autonomy (i.e., the "core" eudaimonic components of PWB). Nonreactivity and
nonjudging (i.e., the mindfulness "how" skills) were negatively associated with
neuroticism aspects, such as withdrawal (e.g., depression) and volatility (e.g.,
anger). Describing and nonreactivity were the only mindfulness skills
significantly correlated with the SWB measures. Acting with awareness mediated
the effect of both withdrawal and volatility on eudaimonic well-being outcomes.
Describing had consistent mediation effects across all well-being measures, but
only for the withdrawal aspect. Nonreactivity and nonjudging did not mediated
withdrawal when considering eudaimonic well-being as outcomes. Mediation effects
for nonjudging and nonreactivity were found between volatility and SWB markers as
well as between volatility and self-acceptance, environmental mastery, and
positive relations with others (i.e., the "other" eudaimonic PWB components). In
sum, the mindfulness "what" skills were important for eudaimonic well-being,
especially for internalizing individuals. Authors discuss the usefulness of a
facet-level analysis of mindfulness for examining incremental validity of some
facets over others in accounting for different well-being outcomes measures.
Clinical implications are also discussed.
PMID- 28515797
TI - Circulating nucleosomes as new blood-based biomarkers for detection of colorectal
cancer.
AB - BACKGROUND: Colonoscopy is currently widely accepted as the gold standard for
detection of colorectal cancer (CRC) providing detection of up to 95% of pre
cancerous lesions during the procedure. However, certain limitations exist in
most countries including cost and access to the procedure. Moreover, colonoscopy
is an invasive technique with risk inherent to the endoscopic procedure. For this
reason, alternative screening tests, in particular, fecal occult blood-based
tests, have been widely adopted for frontline screening. Limited compliance to
colonoscopy and fecal screening approaches has prompted research on blood-based
tests as an alternative approach to identifying individuals at risk who could
then be referred for colonoscopy. Increased total levels of nucleosomes in the
blood have been associated with tumor burden and malignancy progression. Here, we
report for the first time, CRC-associated epigenetic profiles of circulating cell
free nucleosomes (cf-nucleosomes). METHODS: Levels of 12 epigenetic cf-nucleosome
epitopes were measured in the sera of 58 individuals referred for endoscopic
screening for CRC. RESULTS: Multivariate analysis defined an age-adjusted panel
of four cf-nucleosomes that provided an AUC of 0.97 for the discrimination of CRC
from healthy controls with high sensitivity at early stages (sensitivity of 75
and 86 at 90% specificity for stages I and II, respectively). A second
combination of four cf-nucleosome biomarkers provided an AUC of 0.72 for the
discrimination of polyps from the healthy group. CONCLUSIONS: This study suggests
that a combination of different cf-nucleosome structures analyzed in serum
samples by a simple ELISA is a promising approach to identify patients at risk of
CRC.
PMID- 28515798
TI - Epigenome-wide association of myocardial infarction with DNA methylation sites at
loci related to cardiovascular disease.
AB - BACKGROUND: Development of cardiovascular disease (CVD), including coronary
artery disease, arrhythmia, and ischemic stroke, depends on environmental and
genetic factors. To investigate the epigenetic basis of myocardial infarction
(MI), we performed an epigenome-wide association study for this condition in
elderly Japanese subjects. A total of 192 case subjects with MI and 192 control
subjects were recruited from hospital attendees and the general population,
respectively. Genome-wide DNA methylation (DNAm) profiles for DNA isolated from
whole blood were obtained by analysis with an Infinium HumanMethylation450
BeadChip. The relation of DNAm sites found to be significantly associated with MI
to nearby single nucleotide polymorphisms (SNPs) previously shown to be
associated with CVD was assessed in the control group. FINDINGS: Three DNAm sites
(cg06642177, cg07786668, cg17218495) showed genome-wide significant associations
with MI (p = 4.33 * 10-8, 3.96 * 10-10, and 3.77 * 10-8, respectively). Two of
these sites (cg07786668, cg17218495) still showed such associations after
adjustment for classical risk factors of MI (p = 1.04 * 10-7 and 6.60 * 10-8,
respectively). The DNAm sites cg07786668 and cg17218495 are located in ZFHX3
(zinc finger homeobox 3) and SMARCA4 (SWI/SNF-related, matrix-associated, actin
dependent regulator of chromatin, subfamily a, member 4) genes, respectively.
SNPs in ZFHX3 or SMARCA4 that were previously found to be associated with CVD
were not significantly associated with these DNAm sites in our control subjects.
CONCLUSIONS: We identified two DNAm sites-cg07786668 in ZFHX3 and cg17218495 in
SMARCA4- that are independently and significantly associated with MI. Our results
suggest that the development of MI might be influenced by changes in DNAm at
these sites via a pathway that differs from that affected by CVD-associated SNPs
in these genes. The Kita-Nagoya Genomic Epidemiology (KING) study, which was the
source of control samples in the present study, was registered in
ClinicalTrials.gov (NCT00262691) on 6 December 2005.
PMID- 28515802
TI - From cue cards to code rot: In the end, it's not how you acquire the content,
it's what you do with it.
PMID- 28515803
TI - Don't miss your 2017 Canadian Urological Association annual meeting.
PMID- 28515801
TI - Effectiveness and Usability of a Web-Based Mindfulness Intervention for Families
Living with Mental Illness.
AB - Families living with mental illness express needs of support and experiences of
burden that may affect their own health detrimentally and hence also their
ability to support the patient. Mindfulness-based interventions have shown
beneficial health effects in both clinical and healthy populations. The aim of
the current study was to explore the effectiveness and usability of a web-based
mindfulness program for families living with mental illness, which was first
tested in a feasibility study. The study was designed as a randomized controlled
trial with an experiment group and a wait-list control group with assessments on
primary and secondary outcomes at baseline, post-intervention, and at a 3-month
follow-up. Significant positive improvements in mindfulness and self-compassion,
and significant decreases in perceived stress and in certain dimensions of
caregiver burden were found, with good program usability. Easily accessible
mindfulness-based interventions may be useful in addressing caregivers' needs of
support and in preventing further ill health in caregivers. Further studies are
needed, among others, to further customize interventions and to investigate the
cost-effectiveness of such programs.
PMID- 28515804
TI - Study habits of Canadian urology residents: Implications for development of a
competence by design curriculum.
AB - INTRODUCTION: The purpose of this study was to evaluate the study habits of
Canadian urology residents throughout their residency training. METHODS: A survey
was administered to all final-year Canadian urology residents over a two-year
period. Sixty-seven respondents answered a survey consisting of 54 questions
scored on a 10-point Likert score. The survey addressed study habits throughout
training, motivations for studying, and preferred resources used. RESULTS:
Dedication to studying was directly correlated with proximity to the Royal
College of Physicians and Surgeons of Canada (RCPSC) exam. Ninety-six percent of
residents reported studying over 10 hours per week during their chief year
compared to 0% during their junior year. As residents progressed in their
training, preparation for the Royal College exam became the greatest motivator
for studying. There was considerable variability in study methods and study
resources used throughout training. In their chief year, residents found such
resources as the textbook Campbell-Walsh, AUA updates, CUA and AUA guidelines,
and the study notes of former trainees to be valuable for their preparation.
Teaching rounds, journal clubs, and reading current urological literature were
found to be les helpful. Forty-six percent of all residents surveyed indicated
that they would prefer writing their RCPSC exam one year earlier than the current
timing. CONCLUSIONS: This study provides insight into study habits of Canadian
urology residents. This data may be helpful in shaping the future of urology
training programs and examinations within Canada and elsewhere.
PMID- 28515805
TI - Is computed tomography-defined obstruction a predictor of urological intervention
in emergency department patients presenting with renal colic?
AB - INTRODUCTION: Our objective was to determine whether unilateral calculus-induced
ureteric obstruction on computed tomography (CT) was independently associated
with the need for urological intervention and 30-day return to the emergency
department (ED). METHODS: We performed a retrospective cohort study of patients
with symptomatic urinary calculi diagnosed by unenhanced helical CT. Stepwise
regression analysis was used to determine the predictors of urological
intervention and 30-day return to the ED. Potential predictors assessed included:
patient demographics, calculus size, calculus location, degree of obstruction,
analgesic doses, signs and symptoms of infection, serum creatinine, cumulative
intravenous fluid administered, and the prescription of medical expulsive
therapy. RESULTS: Of 195 patients, 81 (41.5%) underwent urological intervention.
The size of the calculus, its location, and the cumulative opioid dose were all
independent predictors for urological intervention. Every 1 mm increase in
calculus size increased the likelihood of intervention 2.2 times (odds ratio [OR]
2.17; 95% confidence interval [CI] 1.67-2.85). Proximal stones were 4.7 times
more likely to require intervention than distal calculi (OR 0.21; 95% CI 0.09
0.49). Every 10 mg increase in morphine was associated with a 30% increase in the
odds of intervention (OR 1.30; 95% CI 1.07-1.58). Degree of obstruction was not
associated with the need for urological intervention. Finally, none of the
variables were predictors for 30-day return to the ED. CONCLUSIONS: Although
stone size, proximal location, and severe pain, as indicated by higher opioid
doses, were associated with the need for intervention, the degree of obstruction
did not influence the management of patients with CT-defined urinary calculi.
PMID- 28515806
TI - Larger proximal ureteral stones with severe pain, rather than computed tomography
defined ureteral obstruction, are associated with urological intervention.
PMID- 28515808
TI - Clinical risk-stratification for prostate cancer: Where are we, and where do we
need to go?
PMID- 28515807
TI - External validation of the ProCaRS nomograms and comparison of existing risk
stratification tools for localized prostate cancer.
AB - INTRODUCTION: The purpose of this study was to perform a direct comparison of
several existing risk-stratification tools for localized prostate cancer in terms
of their ability to predict for biochemical failure-free survival (BFFS). Two
large databases were used and an external validation of two recently developed
nomograms on an independent cohort was also performed in this analysis. METHODS:
Patients who were treated with external beam radiotherapy (EBRT) and/or
brachytherapy for localized prostate cancer were selected from the multi
institutional Genitourinary Radiation Oncologists of Canada (GUROC) Prostate
Cancer Risk Stratification (ProCaRS) database (n=7974) and the Centre Hospitalier
de l'Universite de Montreal (CHUM) validation database (n=2266). The primary
outcome was BFFS using the Phoenix definition. Concordance index (C-index)
reported from Cox proportional hazards regression using 10-fold cross validation
and decision curve analysis (DCA) were used to predict BFFS. RESULTS: C-index
identified Cancer of the Prostate Risk Assessment (CAPRA) score and ProCaRS as
superior to the historical GUROC and National Comprehensive Cancer Network (NCCN)
risk-stratification systems. CAPRA modeled as five and three categories were
superior to GUROC and NCCN only for the CHUM database. C-indices for CAPRA score,
ProCaRS, GUROC, and NCCN were 0.72, 0.72, 0.71, and 0.72, respectively, for the
ProCaRS database, and 0.66, 0.63, 0.57, and 0.60, respectively, for the CHUM
database. However, many of these comparisons did not demonstrate a clinically
meaningful difference. DCA identified minimal differences across the different
risk-stratification systems, with no system emerging with optimal net benefit.
External validation of the ProCaRS nomograms yielded favourable calibrations of
R2=0.778 (low-dose rate [LDR]-brachytherapy) and R2=0.868 (EBRT). CONCLUSIONS:
This study externally validated two ProCaRS nomograms for BFFS that may help
clinicians in treatment selection and outcome prediction. A direct comparison
between existing risk-stratification tools demonstrated minimal clinically
significant differences in discriminative ability between the systems, favouring
the CAPRA and ProCaRS systems. The incorporation of novel prognostic variables,
such as genomic markers, is needed.
PMID- 28515809
TI - Prospective evaluation of anxiety, pain, and embarrassment associated with
cystoscopy and urodynamic testing in clinical practice.
AB - INTRODUCTION: We sought to prospectively assess anxiety, pain, and embarrassment
associated with diagnostic cystoscopy and multi-channel urodynamic study (UDS).
METHODS: All consecutive patients undergoing diagnostic cystoscopy or UDS in our
department over a period of nine months were asked to participate. Two anonymous
auto-administered questionnaires were specifically designed to collect basic
epidemiological data, document medical history, and assess the quality of
information provided, along with prevalence and level (0-10 numerical visual
analog rating scale) of anxiety, pain, and embarrassment experienced before
and/or during the procedures. Statistical analysis was carried out to identify
underlying factors that could have influenced patients' experience and ascertain
potential correlations between anxiety, pain, and embarrassment. RESULTS: 101 and
185 patients were respectively evaluated immediately after cystoscopy and UDS.
Multivariate analysis repeatedly showed statistical correlations between anxiety,
pain, and embarrassment, with regard to prevalence and level of intensity in both
cystoscopy and UDS populations. Males and young patients were more likely to
present anxiety, pain, or embarrassment during cystoscopy and UDS. Interestingly,
patients who reported having received complete information before cystoscopy were
significantly more likely to experience anxiety (62.6% vs. 20.0%; p=0.009).
CONCLUSIONS: The present study demonstrated the major impact of gender and age on
patients' experience. Interestingly, information provided before cystoscopy was
reported to have a negative impact on patients' perception of anxiety; this could
be partly prevented by optimizing the way information is provided to patients.
PMID- 28515810
TI - Avoid the embarrassment: Use the right tools for the right job.
PMID- 28515811
TI - First-line sunitinib or pazopanib in metastatic renal cell carcinoma: The
Canadian experience.
AB - INTRODUCTION: Clinical trial data has shown pazopanib to be non-inferior in
overall survival (OS) compared to sunitinib as first-line treatment for
metastatic renal cell carcinoma (mRCC). The purpose of this study was to evaluate
outcomes and compare dose-modifying toxicities of mRCC patients treated with
suntinib or pazopanib in the real-world setting. METHODS: Data were collected on
mRCC patients using the prospective Canadian Kidney Cancer Information System
(CKCis) database from January 2011 to November 2015. Statistical analyses were
performed using Cox regression adjusted for several risk factors and the Kaplan
Meier method. RESULTS: We identified 670 patients treated with sunitinib (n=577)
and pazopanib (n=93). There were no significant differences in International
Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups (p=0.807).
Patients treated with sunitinib had improved OS compared with pazopanib (median
31.7 vs. 20.6 months, p=0.028; adjusted hazard ratio [aHR] 0.60; 95% confidence
interval [CI] 0.38-0.94). Time to treatment failure (TTF) was numerically, but
not statistically, improved with sunitinib (medians 11.0 vs. 8.4 months, p=0.130;
aHR 0.87; 95% CI 0.59-1.28). Outcomes with individualized dosing on sunitinib
were unavailable for this analysis. Patients treated with sunitinib had a higher
incidence of mucositis, hand-foot syndrome, and gastroesophageal reflux disease;
patients treated with pazopanib had a higher incidence of hepatotoxicity.
CONCLUSIONS: In Canadian patients with mRCC, treatment with sunitinib appears to
be associated with an improved OS compared to pazopanib in the first-line
setting. Patient selection factors and the contemporary practice of
individualized dosing with sunitinib may contribute to these real-world outcomes
and warrant further investigation.
PMID- 28515812
TI - Cost-effectiveness of mirabegron compared to tolterodine ER 4 mg for overactive
bladder in Canada.
AB - INTRODUCTION: This analysis compared the cost-effectiveness of once-daily
regimens of mirabegron 50 mg and generic tolterodine ER 4 mg in a hypothetical
cohort of previously treated patients with overactive bladder (OAB) in Canada.
METHODS: A Markov model was developed to represent different health states
according to OAB symptoms (frequency, incontinence), presence/absence of adverse
events (AEs; dry mouth, constipation, blurred vision), and treatment status (on
treatment, discontinue treatment, restart previous treatment). The time horizon
used was one year, with monthly transitions between health states. The model was
populated using data from a phase 3, placebo-controlled trial of mirabegron that
included tolterodine as an active comparator (SCORPIO), as well as other
published literature and expert opinion. Cost-effectiveness was calculated from
Canadian public payer (based on Quebec list prices) and societal perspectives.
RESULTS: The incremental one-year cost per patient for mirabegron over
tolterodine was $182 CAD and $157 CAD from the payer and societal perspectives,
respectively. The incremental quality-adjusted life year (QALY) gain for
mirabegron was 0.0066 when using EQ-5D health-state utilities. Mirabegron was
cost-effective compared with tolterodine, from both payer and societal
perspectives, and remained cost-effective vs. tolterodine across the majority of
sensitivity analyses. The model was based on limited clinical trial evidence
supplemented with expert opinion and assumptions; a select number of OAB
symptoms, AEs, and direct and indirect medical costs associated with OAB; and a
timeframe of only one year. CONCLUSIONS: From the payer and societal
perspectives, the health economic model indicates that in Canada, mirabegron is a
cost-effective treatment strategy compared with tolterodine, leading to improved
health outcomes (QALYs) at an acceptable incremental cost.
PMID- 28515813
TI - Transperitoneal laparoscopic nephrectomy: Assessing complication risk in cases of
previous abdominal surgery.
AB - INTRODUCTION: We aimed to assess the effect of previous abdominal surgery on
perioperative outcomes in patients undergoing transperitoneal laparoscopic
partial (LPN) or radical (LRN) nephrectomy for renal masses. METHODS: We
retrospectively reviewed all cases of LPN and LRN for renal masses at our
institution between 2008 and 2014. Patients were divided in two groups, those
with and without prior abdominal surgery. Four perioperative outcomes were
compared, namely, operative time (OT), estimated blood loss (EBL), length of stay
(LOS), and 30-days complications rate. A subanalysis was performed to address the
impact of previous open cholecystectomy on right LPN or LRN. RESULTS: Of 293
patients identified, 146 (49.8%) had previous abdominal surgery. In univariate
analysis, no differences in operative time (136 vs. 144 minutes; p=0.154), EBL
(88 vs. 100 mL; p=0.211), or 30-day complication rate (24 vs. 14%; p=0.069) were
recorded between the groups. Only LOS favoured patients without previous
abdominal surgery (3 vs. 4 days; p=0.001). In multivariate analysis, prior
abdominal surgery was not associated with an increased OT, EBL, LOS, or
complication rate. The analysis of right nephrectomies showed increased OT (148
vs. 128 minutes; p=0.049) and complication rate (42 vs. 16%; p=0.004) for
patients with past open cholecystectomy compared to those without. Multivariate
analysis revealed that prior open cholecystectomy was associated with a longer
LOS (ORmedian=2.7 [1.2-8.0]) and an increased risk of complications (ORmedian=4.5
[1.6-10.5]). CONCLUSIONS: In this cohort, previous abdominal surgery was not
associated with worse perioperative outcomes after transperitoneal LPN and LRN
for renal masses. However, previous open cholecystectomy resulted in a higher
risk of complication and a longer LOS in patients undergoing right laparoscopic
nephrectomy.
PMID- 28515815
TI - ?
PMID- 28515814
TI - A review of routinely collected data studies in urology: Methodological
considerations, reporting quality, and future directions.
AB - Studies using routinely collected data (RCD) are common in the urological
literature; however, there are important considerations in the creation and
review of RCD discoveries. A recent reporting guideline (REporting of studies
Conducted using Observational Routinely-collected health Data, RECORD) was
developed to improve the reporting of these studies. This narrative review
examines important considerations for RCD studies. To assess the current level of
reporting in the urological literature, we reviewed all the original research
articles published in Journal of Urology and European Urology in 2014, and
determined the proportion of the RECORD checklist items that were reported for
RCD studies. There were 56 RCD studies identified among the 608 articles. When
the RECORD items were considered applicable to the specific study, they were
reported in 52.5% of cases. Studies most consistently (>80% of them) reported the
names of the data sources, the study time frame, the extent to which the authors
could access the database source, the patient selection, and discussed missing
data. Few studies (<25%) discussed validation of key coding elements, details on
data-linkage, data-cleaning, the impact of changing eligibility over time, or
provided the complete list of coding elements used to define key study variables.
Reporting factors specifically relevant in RCD studies may serve to increase the
quality of these studies in the urological literature. With increased
technological integration in healthcare and the proliferation of electronic
medical records, RCD will continue to be an important source for urological
research.
PMID- 28515816
TI - Impact of smartphone digital photography, email, and media communication on
emergency room visits post-hypospadias repair.
AB - INTRODUCTION: Advances in communication technology are shaping our medical
practice. To date, there is no clear evidence that this mode of communication
will have any effect on unnecessary postoperative emergency room (ER) visits. We
aim to evaluate the effect of email and media communication with application of
smartphone digital photography on post-hypospadias repair ER visit rates.
METHODS: This prospective cohort study included all patients who underwent
hypospadias repair performed by a single surgeon from October 2014 to November
2015. Patients were categorized into two groups: Group A consented for smartphone
photography and email communication and Group B declined. Reason for ER visits
within 30 days postoperatively was assessed by another physician, who was blinded
of patient group assignment. The reasons were categorized as: unnecessary ER
visit, indicated ER visit, or visit unrelated to hypospadias surgery. Chi-square
test and T-test were used for statistical analysis. Relative risk (RR) and
corresponding 95% confidence interval (CI) were also calculated. Statistical
significance was set at p<0.05. RESULTS: Over a 14-month period, 96 patients
underwent hypospadias repair (81 in Group A, 15 in Group B 5). No significant
difference was noted between groups for overall ER return rate (RR 0.46, 95% CI
0.21, 1.0). However, the number of ER visits for wound check not requiring
intervention was significantly lower in Group A than in Group B (RR 0.14, 95% CI
0.035, 0.56); likewise, a higher number of ER visits requiring intervention was
noted in Group A compared with Group B, although statistically this was not
significant (RR 1.67, 95% CI 0.23, 12.21). CONCLUSIONS: Email communication with
the use of smartphone digital photography significantly reduced the number of
unnecessary ER visits for post-hypospadias wound checks.
PMID- 28515817
TI - Systematic review of the potential role of cannabinoids as antiproliferative
agents for urological cancers.
AB - INTRODUCTION: The palliative effects of cannabis sativa (marijuana), which
include appetite stimulation, attenuation of nausea and emesis, and pain relief,
are well known. The active components of cannabis sativa (cannabinoids) and their
derivatives have received growing interest due to their diverse pharmacological
activities, such as cell growth inhibition and tumour regression. The aim of this
review is to look at the current evidence on the antiproliferative effects of
cannabinoids in urological malignancies, including renal, prostate, bladder, and
testicular cancers. METHODS: We conducted a systematic review of studies
exploring the effect of cannabinoids on tumour activity, including all study
types except expert opinions. A formal search was run on Medline database from
1946 to September 2016, along with a hand-search on PubMed for relevant studies.
RESULTS: The search yielded a total of 93 studies from Medline and PubMed, of
which 23 studies were included in the final analysis. To date, there are various
in vitro studies elucidating the potential mechanism of action of cannabinoids
for urological cancers, along with population-based studies specifically for
testicular malignancies. To date, no clinical trials have been conducted for
urological cancer patients. CONCLUSIONS: These results demonstrate that the role
of endocannabinoids for urological malignancies is an area of active research.
Further research is required not only to evaluate the crosstalk between cancer
signaling pathways and cannabinoids, but also large randomized clinical studies
with urological patients need to be conducted before cannabinoids can be
introduced as potential therapeutic options for urological neoplasms.
PMID- 28515818
TI - Pharmacogenomic Testing for Psychotropic Medication Selection: A Systematic
Review of the Assurex GeneSight Psychotropic Test.
AB - BACKGROUND: A large proportion of the Ontario population lives with a diagnosed
mental illness. Nearly 5% of Ontarians have major depressive disorder, and
another 5% have another type of depressive disorder, bipolar disorder,
schizophrenia, anxiety, or some other disorder not otherwise specified.
Medications are commonly used to treat mental illness, but choosing the right
medication for each patient is challenging, and more than 40% of patients
discontinue their medication within 90 days because of adverse effects or lack of
response. The Assurex GeneSight Psychotropic test is a pharmacogenomic panel that
provides clinicians with a report to guide medication selection that is unique to
each patient based on their individual genetic profile. However, it is uncertain
whether guided treatment using GeneSight is effective compared with unguided
treatment (usual care). METHODS: We performed a systematic review to identify
English-language studies published before February 22, 2016, that compared
GeneSight-guided care and usual care among people with mood disorders, anxiety,
or schizophrenia. Primary outcomes of interest were prevention of suicide,
remission of depression symptoms, response to depression therapy, depression
score, and quality of life. Secondary outcomes of interest were impact on
therapeutic decisions and patient and clinician satisfaction. Risk of bias was
evaluated, and the quality of the evidence was assessed using the Grading of
Recommendations Assessment, Development, and Evaluation (GRADE) working group
criteria. RESULTS: Four studies met the inclusion criteria. These studies used a
version of GeneSight that included the CYP2D6, CYP2C19, CYP1A2, SLC6A4, and HTR2A
genes; one of the studies also included CYP2C9. Patients who received the
GeneSight test to guide psychotropic medication selection had improved response
to depression treatment, greater improvements in measures of depression, and
greater patient and clinician satisfaction compared with patients who received
treatment as usual. We observed no differences in rates of complete remission
from depression. The findings were based on GRADE assessment of low to very low
quality evidence, and the body of evidence had several limitations: the included
studies used an older version of GeneSight and were limited to a population with
major depression, so results may not be generalizable to other versions of the
test or different populations such as patients with anxiety or schizophrenia.
CONCLUSIONS: There is uncertainty about the use of GeneSight Psychotropic
pharmacogenomic genetic panel to guide medication selection. It was associated
with improvements in some patient outcomes, but not others. As well, our
confidence in these findings is low because of limitations in the body of
evidence.
PMID- 28515819
TI - Sub-Clinical Hypothyroidism and Its Association With Increased Cardiovascular
Mortality: Call for Action.
AB - Thyroid hormones play an important role in regulating different functions
regarding metabolism and performance in multiple organs. Any change in the
thyroid hormones axis can lead to profound effect on the vital organ stability
especially the cardiovascular system. Hypothyroidism is classified according to
the clinical presentation as overt and subclinical. Currently, there exists a
paucity of evidence on the beneficial effects of thyroxine hormone replacement on
cardiovascular mortality outcomes in subclinical hypothyroidism. Also, the
clinical relevance of measuring and treating supra-normal thyroid-stimulating
hormone levels in newly diagnosed heart failure patients with preserved ejection
fraction requires further study. Here we review the current evidence regarding
the prognostic significance of sub-clinical hypothyroidism in patients with heart
failure with preserved ejection fraction.
PMID- 28515820
TI - Arterial Velocity Pulse Index as a Novel Marker of Atherosclerosis Using Pulse
Wave Analysis on High Sensitivity Troponin T in Hypertensive Patients.
AB - BACKGROUND: The arterial velocity pulse index (AVI) is explored as a novel marker
of atherosclerosis using pulse wave analysis in clinical settings. Recent
clinical studies have reported that the level of high-sensitivity troponin T (hs
cTnT) is an important biomarker in hypertensive patients. The aim of this study
was to clarify the impact of AVI on hs-cTnT in these patients. METHODS: This
study enrolled 455 hypertensive outpatients (181 males and 274 females; mean age,
65 +/- 11 years (mean +/- standard deviation)) without a history of
cardiovascular events. AVI and hs-cTnT levels were measured using a commercial
device, and relations among various clinical parameters, including AVI and hs
cTnT, were examined. RESULTS: Hs-cTnT was detected in 405 patients (89.0%). AVI
was significantly higher in patients with detectable hs-cTnT than in those
without (28 +/- 7 vs. 24 +/- 8, respectively, P < 0.001). In patients with
detectable hs-cTnT, there was a significant positive correlation between AVI and
hs-cTnT (r = 0.42, P < 0.001). Furthermore, multiple regression analyses revealed
that AVI was an independent variable when hs-cTnT was used as a subordinate
factor. On the other hand, hs-cTnT age, Cornell electrocardiographic voltage,
height, urinary albumin excretion, pulse rate, and derivatives of reactive oxygen
metabolites test were independent variables when AVI was used as a subordinate
factor. CONCLUSION: The results of this study indicate that AVI reflects features
of arterial wave reflection and is an important factor for hs-cTnT elevation in
hypertensive patients.
PMID- 28515822
TI - Primary Percutaneous Coronary Intervention Angioplasty of Occluded Twin
Circumflex Coronary Artery in a Patient of Acute Inferior Wall Myocardial
Infarction: A Rare Anomaly.
AB - Anomalies of the coronary arteries are reported in 1-2% of patients among
diagnostic angiogram. Dual origin of a circumflex from both sinuses is extremely
rare among them. We report a case of a patient who underwent primary percutaneous
coronary intervention for acute inferior wall myocardial infarction where left
coronary injection demonstrated normal obtuse marginal and right coronary
injection demonstrated normal right coronary artery (RCA). On further probing, an
anomalous left circumflex (LCx) artery was seen arising from RCA ostium which was
subsequently cannulated and revascularized by deployment of 2.75 * 26 mm Xience
Prime drug-eluting stent (Abott Vascular, USA). Herein, we report for the first
time primary percutaneous coronary intervention of twin circumflex and also
illustrate that anomalous circumflex can be missed if it arises from RCA ostium
and if not probed carefully.
PMID- 28515821
TI - Left Ventricular Velocity of Propagation: A Useful Non-Invasive Measurement When
Assessing Hemodynamic Alterations in Pulmonary Arterial Hypertension.
AB - BACKGROUND: Left ventricular (LV) velocity of propagation (Vp) has been shown to
be inversely related to the LV relaxation time constant. We sought to examine Vp
from a group of chronic pulmonary hypertension (cPH) patients and compare these
values to Vp obtained in normal individuals and patients with known LV diastolic
dysfunction (LVDD). METHODS: Echo-Doppler data and Vp measurements were
retrospectively collected from all patients. The studied population was divided
into four groups. Group I comprised of 15 patients with normal LV diastole, group
II included 27 patients with stage 1 LVDD, group III was made up of 27 patients
with stage 2 LVDD, and group IV included 66 patients with cPH. RESULTS: In the
cPH population studied, patients had smaller end-diastolic LV cavities with the
highest Vp values but their early mitral inflow to Vp ratios were not different
from healthy controls. In addition, Vp values and pulmonary wedge capillary
pressures were significantly associated in patients with LV dysfunction or
pulmonary hypertension (P < 0.01). CONCLUSIONS: LVVp might be a useful non
invasive measurement to be routinely obtained in cPH patients as it probably not
only reflects the compressive forces being exerted on the LV, known to increase
Vp, but also might be quite useful for the non-invasive assessment of pulmonary
capillary wedge pressures in these patients.
PMID- 28515823
TI - Lupus-Negative Libman-Sacks Endocarditis Complicated by Catastrophic
Antiphospholipid Syndrome.
AB - Libman-Sacks endocarditis is characterized by sterile and verrucous lesions that
predominantly affect the aortic and mitral valves. In most cases, patients do not
have significant valvular dysfunction. However, patients with significant
valvular dysfunction may present with serious complications such as cardiac
failure, arrhythmias, and thromboembolic events. Recently, association of Libman
Sacks endocarditis with antiphospholipid antibody syndrome (APS) has been made.
APS is most commonly defined by venous and arterial thrombosis, recurrent
pregnancy loss, and thrombocytopenia. While the syndrome can be a primary
syndrome, it is usually secondary to systemic lupus erythematosus. Catastrophic
antiphospholipid syndrome (CAPS) can be a life-threatening presentation of APS
and can occur in 1% of patients with antiphospholipid syndrome. We present a very
rare case of a young female patient with lupus-negative Libman-Sacks endocarditis
complicated by CAPS.
PMID- 28515824
TI - Cardiogenic Shock, Acute Severe Mitral Regurgitation and Complete Heart Block
After Cavo-Tricuspid Isthmus Atrial Flutter Ablation.
AB - Radiofrequency (RF) ablation is the first-line management of cavo-tricuspid
isthmus dependent atrial flutter. It has been performed with 95% success rate.
Adverse events are very rare. We report the first case of acute severe mitral
regurgitation (MR) and complete heart block developed after successful atrial
flutter ablation. A 62-year-old female with mild MR presented with palpitations.
Surface electrocardiogram was suggestive of isthmus dependent atrial flutter. A
duodecapolar mapping catheter showed an atrial flutter with cycle length of 280
ms. An 8 mm tipped Thermistor RF ablation catheter was placed at the cavo
tricuspid isthmus. RF energy was delivered as the catheter was dragged to the
inferior vena cava. Temperature limit was 60 degrees C; the power output limit
was 60 W. The patient converted to sinus rhythm with the first ablation line. Bi
directional block was recorded. Two additional ablation lines lasting 60 - 120 s
were delivered. The patient started having chest pain and developed complete
heart block with no escape rhythm. She became hypotensive and was immediately
paced from the right ventricle. There were no signs of pericardial tamponade.
Emergent bedside echo demonstrated severe MR with a retracted posteromedial
mitral valve leaflet. She was 100% paced and EKG changes could not be assessed.
Based on the sudden onset chest pain, hypotension, complete heart block and acute
severe MR after ablation, the right coronary artery occlusion was suspected. She
was immediately transferred to the catheterization laboratory. Coronary
angiography revealed a total occlusion of the posterolateral branch from the
right coronary artery. Balloon angioplasty and coronary artery stenting was
performed. Complete heart block subsequently resolved. Subsequent bedside
echocardiogram showed marked improvement of the MR. Patients with smaller body
size have smaller hearts and more likely to have injury from RF current. Higher
energy penetrates deeper and causes more tissue damage. The use of lower
temperature limits (55 degrees C) and lower energy (60 W) for small, elderly,
and female patients is encouraged.
PMID- 28515825
TI - Late Presentation of Aortic Aneurysm and Dissection Following Cardiac
Catheterization.
AB - We report a 63-year-old female with hypertension, hyperlipidemia, and prior
pacemaker insertion for atrial fibrillation with symptomatic bradycardia, who was
admitted with substernal chest pressure and diaphoresis. Her electrocardiogram
revealed atrial fibrillation with demand ventricular pacing and her cardiac
biomarkers were negative for acute coronary syndrome. Echocardiogram revealed
normal left ventricular systolic function and normal aortic root diameter.
Coronary angiography revealed 60-70% obtuse marginal lesion, otherwise mild
disease. She was treated medically and discharged in stable condition. She was
readmitted 1 month later with recurring chest pain, and shortness of breath which
started shortly after her most recent discharge. Blood pressure was 152/93 mm Hg,
and heart rate was 105 bpm. BNP was elevated at 1,400 pg/mL, and other cardiac
biomarkers were negative. She was treated with diuretics, which resulted in
decrease of her blood pressure to 81/51 mm Hg. Repeat echocardiogram revealed
severely dilated aortic root, measuring 6.7 cm, with aortic dissection flap and
moderate to severe aortic regurgitation. CT angiogram revealed aortic dissection
extending proximally to the aortic root above the coronary ostia and distally to
the left subclavian artery takeoff. She underwent surgery; she, however, could
not be weaned off from cardiopulmonary bypass and died in the operating room.
This case illustrates the importance of having a high index of suspicion for
iatrogenic aortic dissection following cardiac catheterization as a cause of
recurrence of cardiac symptoms, as early detection may help avert a catastrophic
outcome, as we report in our patient.
PMID- 28515826
TI - Successful Restoration of Complete Heart Block to Normal Sinus Rhythm by Primary
Angioplasty of Dual Left Anterior Descending Artery.
AB - Dual left anterior descending (LAD) artery is a rare coronary anomaly. We present
a patient with a rare case of dual LAD, smaller one arising from the left main
coronary stem and larger one from right coronary artery who presented with acute
anterior wall myocardial infarction with complete heart block (CHB). Temporary
pacemaker was implanted and coronary angiogram revealed critical occlusion of
proximal LAD which was subsequently revascularized by primary angioplasty using
drug-eluting stent (Xience prime, 2.75 * 23 mm) leading to recovery of CHB and
restoration to normal rhythm. To the best of our knowledge, this is the first
reported case of dual LAD presenting with CHB treated by primary angioplasty
reported in the literature.
PMID- 28515827
TI - Transient Left Bundle Branch Block due to Severe Hyperkalemia.
AB - Hyperkalemia is a potentially life-threatening electrolyte imbalance that can
lead to sudden death from cardiac arrhythmias and asystole. We present a case of
transient left bundle branch block pattern on an electrocardiogram (ECG)
secondary to hyperkalemia in a patient with history of end-stage renal disease. A
52-year-old man presented to the emergency room (ER) with chief complaints of
weakness and lethargy after missing his regularly scheduled session of
hemodialysis. A 12-lead ECG in the ER showed sinus tachycardia at 118 beats/min,
wide QRS complexes, peaked T waves and left bundle branch block-like pattern. The
initial basic metabolic panel revealed a serum potassium level of 8.8 mEq/L.
Subsequently, the patient underwent emergent hemodialysis. Serum chemistry after
hemodialysis showed improvement in serum potassium to 4.3 mEq/L. Repeat ECG
performed after correcting potassium showed dissolution of left bundle branch
block finding.
PMID- 28515828
TI - Primary Percutaneous Coronary Intervention Using BaLloon-Assisted Sliding and
Tracking (BLAST) of Diagnostic Catheter to Negotiate Double Hairpin Loop of
Radial Artery.
AB - During transradial intervention, sharp edge of the guide catheter tip may act
like a "razor-blade" and can prevent the catheter navigation especially in
situation like double hair pin loop. Here, we report primary percutaneous
coronary intervention (PCI) through diagnostic catheter using an innovative
technique, balloon-assisted sliding and tracking (BLAST), to overcome this double
hairpin loop, thus saving time and contrast volume.
PMID- 28515829
TI - Semiparametric Random Effects Models for Longitudinal Data with Informative
Observation Times.
AB - Longitudinal data frequently arise in many fields such as medical follow-up
studies focusing on specific longitudinal responses. In such situations, the
responses are recorded only at discrete observation times. Most existing
approaches for longitudinal data analysis assume that the observation or follow
up times are independent of the underlying response process, either completely or
given some known covariates. We present a joint analysis approach in which
possible correlations among the responses, observation and follow-up times can be
characterized by time-dependent random effects. Estimating equations are
developed for parameter estimation and the resulting estimates are shown to be
consistent and asymptotically normal. A simulation study is conducted to assess
the finite sample performance of the approach and the method is applied to data
arising from a skin cancer study.
PMID- 28515831
TI - The Relationship of Living Environment with Behavioral and Fitness Outcomes by
Sex: an Exploratory Study in College-aged Students.
AB - Although physical activity (PA) is associated with several health benefits, there
is a marked decline during college years, which is an influential period for the
development of health behaviors. This study examined the relationship of
neighborhood and living environment with behavioral (PA and sedentary behavior)
and fitness outcomes by sex. Participants were college students that participated
in a fitness assessment, followed by a survey that measured self-reported
exercise and perception of one's environment (sidewalks, crime, traffic, access
to PA resources in their neighborhood and/or apartment complex). Pearson
correlations examined the relationship between behavioral (moderate and vigorous
PA, sedentary behavior, active travel) and fitness outcomes (VO2max, percent body
fat, body mass index, push-ups, curl-ups, blood lipids and glucose) with
environmental measures separately by sex. Among participants (n=444; female=211,
male n=234) environment was significantly related to PA and fitness, with noted
differences by sex. For males, seeing others exercising in the neighborhood and
in their apartment complex, using neighborhood bike lanes, crime and the number
of PA resources at their apartment complex were associated with behavioral and
fitness outcomes. Among females, sidewalks in the neighborhood, seeing others
exercising, using neighborhood bike lanes and number of PA apartment complex
resources were significantly correlated with fitness and behavioral outcomes.
These findings suggest a possible relationship between students' objectively
measured fitness and their environment for PA. Future implications include the
development of policies to create student housing that supports physical activity
and expansion of campus wellness initiatives to off-campus locations.
PMID- 28515832
TI - A Low Dose Caffeine and Carbohydrate Supplement does not Improve Athletic
Performance during Volleyball Competition.
AB - Dietary supplements are widely used to enhance sport performance and the
combination of carbohydrate and caffeine (CHO+CAF) has yielded particularly high
performance gains. Though the effects of a CHO+CAF supplement have been studied
in a laboratory environment, little research exists on the effects of
supplementation during competition. Therefore, the purpose of this study was to
determine the effects of a CHO+CAF supplement on athletic performance in
competition. Eight female collegiate volleyball players completed three testing
sessions under three different conditions separated by approximately one week
each: CHO+CAF supplement, placebo (PBO), and control (CTL) using a randomized,
cross-over design. Blood glucose (BG) was assessed prior to supplementation and
immediately after set three. The supplement and PBO were administered prior to
play and between sets two and three. Following three sets of play, three
performance tests were completed: vertical jump (VJ), agility (AGL), and repeated
30-m sprint ability (RSA). While CHO+CAF supplementation significantly increased
BG, the performance tests were not different (p>.05) among the testing
conditions. These findings suggest that the amount of the supplement used in this
study is not beneficial to VJ, AGL, and RSA in female volleyball players. As
these performance tests were largely anaerobic and non-glycolytic in nature, the
ergogenicity of the supplement may have been underutilized. Additionally, coaches
and athletes should not only be aware of what ingredients are in the supplements
they choose, but the amount of those ingredients as they may modify the efficacy
of the supplement to impact performance.
PMID- 28515834
TI - Better Health-Related Fitness in Youth: Implications for Public Health
Guidelines.
AB - Public health guidelines for physical activity (PA) behaviors are being updated
with 2018 as a proposed release date. Currently, >=60 minutes of daily PA are
recommended for youth. Thus, the purpose of this study was to investigate the
association between reported days of aerobic PA and health-related fitness (HRF).
Participants included 4448 students in grades 6-8. Self-reported days of >=60
minutes of aerobic PA was obtained. HRF was assessed with FitnessGram.
Discriminant analysis indicated that weekly days of aerobic PA related to HRF.
Adolescents who participated in >=5 days of weekly aerobic PA generally had
better fitness results than those with <=4 days. Chi-square analyses indicated
the highest percentages of adolescents in the FitnessGram Healthy Fitness ZoneTM
(HFZ) for each test item were those with >=5 days of aerobic PA. These findings
provided initial support that the impact of aerobic PA on HRF plateaus at 5 days
per week. Thus, adolescents may be able to improve HRF even if they do not meet
the currently recommended guidelines for daily PA.
PMID- 28515833
TI - Time Course of Changes in Neuromuscular Responses at 30% versus 70% 1 Repetition
Maximum during Dynamic Constant External Resistance Leg Extensions to Failure.
AB - The purpose of the current study was to examine the time course of changes in
neuromuscular responses from the vastus medialis (VM) during low versus high
intensity dynamic constant external resistance (DCER) leg extension muscle
actions to failure. Thirteen men performed DCER leg extensions to failure at 30%
and 70% 1-repetition maximum (1-RM) as well as 1-RM measurements pretest and
posttest. Electromyogaphy and mechanomyographic signals were measured from the
VM. There were no differences in neuromuscular responses pretest versus posttest
1-RM. There were time-dependent differences between the 30% and 70% 1-RM
protocols. The initial phase of the 30% 1-RM protocol exhibited increases in
electromyographic-amplitude and mechanomyographic amplitude, but no changes at
70% 1-RM. The middle phases indicated decreases in mechanomyographic amplitude at
30% 1-RM, but increases in mechanomyographic amplitude at 70% 1-RM. The 70% 1-RM
protocol had earlier decrease in mechanomyographic frequency than 30% 1-RM. Both
protocols in the final phases exhibited increases in electromyographic amplitude
and mechanomyogrpahic-amplitude, but decreases in electromyographic frequency and
mechanomyographic frequency. Low and high intensity DCER leg extensions to
failure have time-dependent differences in neuromuscular responses during the
process of fatigue which suggested that motor unit activation strategies may by
influenced by the intensity of a fatiguing workbout. Thus, examining the time
course of changes in neuromuscular responses during a fatiguing workbout allowed
for the identification of the time-points associated with the onset of fatigue.
PMID- 28515835
TI - The Effect of Acute Hyperglycemia on Muscular Strength, Power and Endurance.
AB - The purpose of this study was to elucidate the impact of acute hyperglycemia on
skeletal muscle strength, power, and endurance. Ten male collegiate athletes (age
21.5 +/- 1.5 years, height 186 +/- 2.03 cm, body mass 108.8 +/- 7.6 kg)
participated in 2 testing sessions, separated by 7 days and randomized for either
high glucose (HG) or control (C) treatment conditions. HG consumed a high glucose
drink (2 g glucose/kg body weight) while controls consumed an isocaloric
nutrition bar (40% protein, 30% fat, and 30% carbohydrate). Blood glucose (BC)
levels for HG and C were tested at 0 (basal) and 30, 60, 90, and 120 minutes
(mins) post consumption. At 30 mins post consumption, HG and C muscular strength
was assessed by a 1RM bench press (BP) test followed by lower body power at 60
mins via vertical jump test. Muscular endurance was examined with a 3-set-to
failure BP test at 90 mins. HG exhibited significantly greater BC values (p<0.05)
at the 30, 60, 90, and 120 minute time points. HG glucose area under the curve
was significantly greater (p<0.05) than C and was positively correlated with
%body fat, a finding that trended towards significance, r = 0.587, n= 10, p =
0.074. There were no between group differences in maximal strength, power or
muscular endurance. Although performance measures were unaffected by acute
hyperglycemia, acute hyperglycemia can be induced and maintained in healthy,
active and young subjects. Despite regular physical activity, excess body fat
negatively impacts glucose metabolism.
PMID- 28515830
TI - How Different Respiratory Rate Patterns affect Cardiorespiratory Variables and
Performance.
AB - This study aims to elucidate how respiratory rate (RR) patterns may affect
respiratory gas exchange variables and performance during incremental intensity-
exercise. 10 healthy young men (mean +/- SD, age: 20.7 +/- 0.5 years, height:
174.3 +/- 5.7 cm, and body mass: 72.6 +/- 10.4 kg) performed three incremental
tests on a cycle ergometer at three different RR (60, 45 and 30 breaths per min)
in each trial. During the tests, tidal volume (TV), minute ventilation (VE),
fractional content of oxygen (FeO2), fractional content of carbon dioxide
(FeCO2), oxygen uptake (VO2), expiratory carbon dioxide (VCO2), equivalent of
oxygen (EqO2), VE/VCO2, and respiratory exchange ratio (RER) were determinate
breath-by-breath. Additionally, exercise time (as a performance marker) was
measured. Statistical analyses for the results were carried out to determine
significant differences between the three trials. VCO2, VO2, and exercise time
did not show statistical differences in the three trials. Therefore, we concluded
that RR affects some respiratory gas exchange variables but does not influence
the VO2max and endurance performance.
PMID- 28515836
TI - College Students' Knowledge of Recovery Beverage Serving Sizes.
AB - Previous research suggests that chocolate milk may be a beneficial recovery
beverage, yet little is known about how athletes and students training for
careers in sports science or health-related fields interpret recommended recovery
beverage serving sizes. This study examined college students' ability to
correctly apply serving size recommendations for chocolate milk and protein
powder used during post-exercise recovery and assessed usual consumption of milk
as a recovery beverage. College students (34 women, 39 men) poured the amount of
chocolate milk they would consume within 90 minutes after exercise unaided and
with the use of a serving size guide. They scooped the amount of protein powder
they would use after exercising. Participants reported consuming about 1.3+/-1.8
glasses of milk and drinking a recovery beverage besides milk an average of
0.95+/-1.3 times in the past three days. The majority poured less than
recommended. Student athletes poured significantly closer to the recommendation
than non-athletes (436+/-128 ml versus 418+/-127 ml, p=0.016) and poured
significantly closer to the recommendation after reviewing a serving size guide
(p=0.038). Athletes and men served themselves significantly more protein powder
than non-athletes (13.0+/-5.6 g versus 10.3+/-5.2 g, p=0.047) and women (12.5+/
6.0 g versus 9.8+/-4.4 g, p=0.041). Most participants reported that the serving
size guide was easy to read and helpful. Nutrition education specific to post
exercise recovery beverages may help students improve accuracy when interpreting
serving size recommendations.
PMID- 28515837
TI - Resistance Training Contribute to the Aerobic Components of an Exercise Session
in Adults but not as Much in Older Adults.
AB - Previous research has indicated that active adults are able to achieve moderate
intensity as measured via heart rate during a typical resistance training (RT)
session. The main objective was to identify if overweight adults and older adults
can reach aerobic moderate intensity at a rate comparable to adults displaying a
recommended body mass index. Twenty participants in each group were asked to
visit a fitness facility twice if they self-reported doing RT for a minimum two
days per week. At the first session baseline characteristics and maximal lifting
capacity for each RT exercise. At the second, intensity was monitored via heart
rate monitor during a RT exercise program composed of 10 exercises targeting
major muscle groups. Three sets of 10 repetitions at 70% of maximal load were
completed for each exercise. Moderate intensity was defined as a minimum of 40%
of heart rate reserve. The proportion of time spent at moderate to vigorous
intensity between the comparison group and the overweight adult group was not
significantly different, with a median (25th-75th) proportion time of 82.6% (69.2
94.6) versus 92.5% (73.3-99.1); p=.54 or an average time of 42 minutes versus 45
minutes. The older adults group, however, spent a lower proportion of time at
moderate to vigorous intensity compared with the comparison group, 51.5% (22.0
86.6) or 24 minutes; p<.01 compared with the comparison group. This study
suggests that a good proportion of time spent doing RT can contribute to an
aerobic component of the international guidelines, and therefore reduce the
weekly time commitment especially for men and women age below 60 years old.
PMID- 28515838
TI - Passion for Academics and Problematic Health Behaviors.
AB - According to the Dualistic Model of Passion (39), passion entails valuing,
liking, and spending time on an activity. The Dualistic Model also posits two
types of passion for activities: harmonious passion (individual voluntarily
engages in the activity) and obsessive passion (individual is compelled to engage
in the activity). The purpose of the present study was to examine the possible
links between college students' passion for academic activities and problematic
health behaviors including smoking, excessive drinking, exercise addiction,
disordered eating, and sleepiness, which is a possible indicator of sleep
deprivation. Participants (n = 502) completed a survey gauging passion type and
health behaviors. Regression analyses revealed obsessive passion for academic
activities was positively associated with scores on measures of excessive
drinking (beta = .15, p= .008), exercise addiction (beta = .19, p<.001), and
disordered eating (beta = .17, p < .001) but was not associated with sleep
deprivation (beta = .07, p = .15). Harmonious passion for academic activities, in
contrast, was negatively associated with excessive drinking behavior (beta =
.16, p = .002) and sleep deprivation (beta = -.13, p = .007) but was not
associated with exercise addiction (beta = .002, p = .97) and disordered eating
(beta = -.04, p = .37). These findings provide further support for the Dualistic
Model of Passion. Students who are obsessively passionate about their academic
activities are more likely to engage in poor health behaviors and, in turn, may
experience greater negative outcomes than students who are harmoniously
passionate about their academics.
PMID- 28515839
TI - Hypotensive Responses of Reciprocal Supersets versus Traditional Resistance
Training in Apparently Healthy Men.
AB - The purpose of this study was to compare the hypotensive responses of reciprocal
supersets (SS) versus traditional training (TRAD) methods. Thirteen men with at
least five years of recreational experience in resistance training (RT)
volunteered for the study. When completing the TRAD protocol, participants
performed the following exercises separately in sequence: chest press (CP), low
row (LR), leg extension (LE), leg curl (LC), pull down (PD), and shoulder press
(SP). The SS method required participants to complete the same exercises as in
the TRAD protocol, but exercises were coupled such that muscles sequentially
served both as an agonist for lift one and then antagonist for lift two and vice
versa. Exercise order used was CP and LR, LE and LC, and PD and SP with 10
repetition maximum loads. Blood pressure (BP) was measured before and for every
10 minutes for one hour after training. There was significantly more total work
(TW) done in the TRAD condition compared to SS. Post exercise hypotension was
evident only after the TRAD session at minutes 30 and 40 for systolic BP.
Significant differences between the TRAD and SS methods were found at 20 minutes,
30 minutes, and 40 minutes for systolic BP. There was no significant two-way
interaction for group * time for diastolic BP. There was a significant two-way
interaction for group * time for mean arterial pressure. Significant reductions
for mean arterial pressure (MAP) occurred only in the TRAD method after 30 to 40
minutes compared to the baseline values. Therefore, a TRAD RT method was
sufficient to cause a hypotensive effect after the training session whereas the
SS method did not reveal significant decreases in BP after the session. However,
these findings are important to elucidate concerns regarding the post-exercise
hypotension after RT and showed that TW might be the key to promote these changes
because the volume of training was shown to be an important training variable to
manipulate and might be associated with BP hypotension after RT.
PMID- 28515840
TI - Self-optimization of Stride Length Among Experienced and Inexperienced Runners.
AB - Experienced runners appear to naturally select a stride length which is optimal
for minimizing oxygen uptake. However, whether this ability is naturally built
into the human body or whether it is learned through experience has not been
previously tested. This study investigated whether inexperienced runners are as
capable as experienced runners of self-optimizing stride length to minimize
oxygen uptake. Thirty-three subjects (nineteen experienced and fourteen
inexperienced) ran for twenty-minutes while preferred and economical stride
lengths were measured. A t-test checked for differences between the experienced
and inexperienced groups in the percent increase of oxygen uptake due to not
running at the most economical stride length. No difference was found between
groups with the increase in oxygen uptake due to not being optimized (p=0.47).
The average percent increase in oxygen uptake above the most economical for
inexperienced and experienced runners was 1.8% and 1.2% respectively. We
concluded that inexperienced and experienced runners are equally capable of
matching preferred stride length to economical stride length, thus athletes and
coaches do not need to alter runner's stride length when economy is the main
concern.
PMID- 28515842
TI - Casein Protein Supplementation in Trained Men and Women: Morning versus Evening.
AB - The purpose of this investigation was to determine the effects of casein
supplementation (54 grams) in the morning (Casein-MOR) or evening (Casein-EVE)
(90 minutes or less prior to sleep) on measures of body composition and exercise
performance in trained men and women. Twenty-six healthy men and women who had
been training regularly for greater than 12 months completed this 8-week study
(mean+/-SD; Casein-MOR group [n=14, seven male, seven female]: 30.0+/-8.2 yr;
170.7+/-9.5 cm; 70.9+/-13.9 kg. Casein-EVE group [n=12, nine male, three female]:
28.9+/-9.5 yr; 172.9+/-7.3 cm; 72.6+/-10.9 kg). Subjects in each group
supplemented with casein protein (54 grams) either in the morning (prior to
12:00pm) or evening (~90 minutes or less prior to sleep). Subjects were advised
to not significantly alter their training program as well as to keep a diary of
their workouts. Body composition was assessed via the Bod Pod(r). In addition,
subjects provided dietary self-reports via MyFitnessPal(r). Approximately 24
daily dietary self-reports were provided from each subject that self-monitored
their diet. The investigators monitored their diet throughout the study. Both the
Casein-MOR and Casein-EVE groups consumed significantly more protein (post versus
pre; p<0.05); however, there were no between-group differences regarding protein
intake. Furthermore, there were no within- or between-group differences for any
other measure. In trained subjects who did not significantly alter their training
program, the addition of 54 grams of casein protein in the morning or evening had
no significant effects on body composition. Furthermore, the additional
consumption of protein calories did not result in an increase in fat mass despite
the fact that exercise volume did not change.
PMID- 28515841
TI - Demands of Simulated Commuting Using an Electrically Assisted Bicycle.
AB - The American College of Sports Medicine (ACSM) recommends adults participate in
weekly aerobic activity for a minimum of 30 minutes moderate intensity exercise 5
days per week or 20 minutes of vigorous activity 3 days per week. The
electrically assisted bicycle may help individuals achieve the ACSM's aerobic
recommendations and introduce inactive individuals to physical activity. To
compare the physiological requirements of riding a bicycle with electric pedal
assist versus non-assist among healthy active young adults. 6 males and 6 females
completed two randomized cycling trials using electric pedal assist (PAB) and non
assist (NON). Cycling trials were completed over a 3.54 km course with varying
terrain. Time to completion was faster in the PAB (12.5 +/- 0.3 min) than the NON
(13.8 +/- 0.3 min, p=0.01). Rating of Perceived Exertion (RPE) was lower in the
PAB (12.0 +/- 0.4) than the NON (14.8 +/- 0.5, p < 0.001). There was no
difference in mean VO2 between PAB (2.3 +/- 0.1 L.min-1) and NON (2.5 +/- 0.1
L.min-1, p=0.45). There was no difference in mean power output when comparing PAB
(115 +/- 11 Watts) to NON (128 +/- 11 Watts, p=0.38). There was no difference in
heart rate between PAB (147 +/- 5 bpm) and NON (149 +/- 5 bpm, p=0.77).
Recreationally active younger (college age) individuals may self-select a similar
physiological intensity of physical activity regardless of mechanical assistance,
resulting in quicker completion of a commuting task with PAB. Both the PAB and
NON exercise bouts met ACSM criteria for vigorous exercise.
PMID- 28515844
TI - Role of circulating microRNAs in liver diseases.
AB - MicroRNAs (miRNAs) are small RNAs regulate gene expression by inhibiting the
turnover of their target mRNAs. In the last years, it became apparent that miRNAs
are released into the circulation and circulating miRNAs emerged as a new class
of biomarkers for various diseases. In this review we summarize available data on
the role of circulating miRNAs in the context of acute and chronic liver diseases
including hepatocellular and cholangiocellular carcinoma. Data from animal models
are compared to human data and current challenges in the field of miRNAs research
are discussed.
PMID- 28515845
TI - Diagnosis of morbid obesity may not impact healthcare utilization for orthotopic
liver transplantation: A propensity matched study.
AB - AIM: To study mortality, length of stay, and total charges in morbidly obese
adults during index hospitalization for orthotopic liver transplantation.
METHODS: The Nationwide Inpatient Sample was queried to obtain demographics,
healthcare utilization, post orthotopic liver transplantation (OLT)
complications, and short term outcomes of OLT performed from 2003 to 2011 (n =
46509). We divided patients into those with [body mass index (BMI) >= 40] and
without (BMI < 40) morbid obesity. Multivariable logistic regression analysis was
performed to characterize differences in in-hospital mortality, length of stay
(LOS), and charges for OLT between patients with and without morbid obesity after
adjusting for significant confounders. Additionally, propensity matching was
performed to further validate the results. RESULTS: Of the 46509 patients who
underwent OLT during the study period, 818 (1.8%) were morbidly obese. Morbidly
obese recipients were more likely to be female (46.8% vs 33.4%, P = 0.002),
Caucasian (75.2% vs 67.8%, P = 0.002), in the low national income quartile (32.3%
vs 22.5%, P = 0.04), and have >= 3 comorbidities (modified Elixhauser index;
83.9% vs 45.0%, P < 0.001). Morbidly obese patient also had an increase in
procedure related hemorrhage (P = 0.028) and respiratory complications (P =
0.043). Multivariate and propensity matched analysis showed no difference in
mortality (OR: 0.70; 95%CI: 0.27-1.84, P = 0.47), LOS (beta: -4.44; 95%CI: -9.93,
1.05, P = 0.11) and charges for transplantation (beta: $15693; 95%CI: -51622
83008, P = 0.64) between the two groups. Morbidly obese patients were more likely
to have transplants on weekdays (81.7%) as compared to those without morbid
obesity (75.4%, P = 0.029). CONCLUSION: Morbid obesity may not impact in-hospital
mortality and health care utilization in OLT recipients. However, morbidly obese
patients may be selected after careful assessment of co-morbidities.
PMID- 28515846
TI - Passive expansion of sub-maximally dilated transjugular intrahepatic
portosystemic shunts and assessment of clinical outcomes.
AB - AIM: To assess for passive expansion of sub-maximally dilated transjugular
intrahepatic portosystemic shunts (TIPS) and compare outcomes with maximally
dilated TIPS. METHODS: Polytetrafluoroethylene covered TIPS (Viatorr) from July
2002 to December 2013 were retrospectively reviewed at two hospitals in a single
institution. Two hundred and thirty patients had TIPS maximally dilated to 10 mm
(mTIPS), while 43 patients who were at increased risk for hepatic encephalopathy
(HE), based on clinical evaluation or low pre-TIPS portosystemic gradient (PSG),
had 10 mm TIPS sub-maximally dilated to 8 mm (smTIPS). Group characteristics
(age, gender, Model for End-Stage Liver Disease score, post-TIPS PSG and clinical
outcomes were compared between groups, including clinical success (ascites or
varices), primary patency, primary assisted patency, and severe post-TIPS HE. A
subset of fourteen patients with smTIPS underwent follow-up computed tomography
imaging after TIPS creation, and were grouped based on time of imaging (< 6 mo
and > 6 mo). Change in diameter and cross-sectional area were measured with 3D
imaging software to evaluate for passive expansion. RESULTS: Patient
characteristics were similar between the smTIPS and mTIPS groups, except for pre
TIPS portosystemic gradient, which was lower in the smTIPS group (19.4 mmHg +/-
6.8 vs 22.4 mmHg +/- 7.1, P = 0.01). Primary patency and primary assisted patency
between smTIPS and mTIPS was not significantly different (P = 0.64 and 0.55,
respectively). Four of the 55 patients (7%) with smTIPS required TIPS reduction
for severe refractory HE, while this occurred in 6 of the 218 patients (3%) with
mTIPS (P = 0.12). For the 14 patients with follow-up computed tomography (CT)
imaging, the median imaging follow-up was 373 d. There was an increase in median
TIPS diameter, median percent diameter change, median area, and median percent
area change in patients with CT follow-up greater than 6 mo after TIPS placement
compared to follow-up within 6 mo (8.45 mm, 5.58%, 56.04 mm2, and 11.48%,
respectively, P = 0.01). CONCLUSION: Passive expansion of smTIPS does occur but
clinical outcomes of smTIPS and mTIPS were similar. Sub-maximal dilation can
prevent complications related to over-shunting in select patients.
PMID- 28515665
TI - Measurement of the WZ production cross section in pp collisions at [Formula: see
text] and 8[Formula: see text] and search for anomalous triple gauge couplings at
[Formula: see text].
AB - The WZ production cross section is measured by the CMS experiment at the CERN LHC
in proton-proton collision data samples corresponding to integrated luminosities
of 4.9[Formula: see text] collected at [Formula: see text], and 19.6[Formula: see
text] at [Formula: see text]. The measurements are performed using the fully
leptonic WZ decay modes with electrons and muons in the final state. The measured
cross sections for [Formula: see text] are [Formula: see text] [Formula: see
text] and [Formula: see text] [Formula: see text]. Differential cross sections
with respect to the [Formula: see text] boson [Formula: see text], the leading
jet [Formula: see text], and the number of jets are obtained using the [Formula:
see text] data. The results are consistent with standard model predictions and
constraints on anomalous triple gauge couplings are obtained.
PMID- 28515848
TI - Coronary artery disease detection - limitations of stress testing in left
ventricular dysfunction.
AB - Incidental diagnosis of left ventricular systolic dysfunction (LVD) is common in
clinical practice. The prevalence of asymptomatic LVD (Ejection Fraction, EF <
50%) is 6.0% in men and 0.8% in women and is twice as common as symptomatic LVD.
The timely and definitive exclusion of an ischemic etiology is central to
optimizing care and reducing mortality in LVD. Advances in cardiovascular imaging
provide many options for imaging of patients with left ventricular dysfunction.
Clinician experience, patient endurance, imaging modality characteristics, cost
and safety determine the choice of testing. In this review, we have compared the
diagnostic utility of established tests - nuclear and echocardiographic stress
testing with newer techniques like coronary computerized tomography and cardiac
magnetic resonance imaging and highlight their inherent limitations in patients
with underlying left ventricular dysfunction.
PMID- 28515847
TI - Pacemaker recycling: A notion whose time has come.
AB - The purpose of this paper is to summarize the need, feasibility, safety,
legality, and ethical perspectives of pacemaker reutilization in low- and middle
income countries (LMICs). It will also describe, in-depth, Project My Heart Your
Heart (PMHYH) as a model for pacemaker reuse in LMICs. The primary source of the
discussion points in this paper is a collection of 14 publications produced by
the research team at the University of Michigan and its collaborative partners.
The need for pacemaker reutilization in LMICs is evident. Numerous studies show
that the concept of pacemaker reutilization in LMICs is feasible. Infection and
device malfunction are the main concerns in regard to pacemaker reutilization,
yet many studies have shown that pacemaker reuse is not associated with increased
infection risk or higher mortality compared with new device implantation. Under
the right circumstances, the ethical and legal bases for pacemaker reutilization
are supported. PMHYH is a proof of concept pacemaker donation initiative that has
allowed funeral home and crematory directors to send explanted devices to an
academic center for evaluation and re-sterilization before donation to
underserved patients in LMICs. The time is now to pursue large-scale studies and
trials of pacemaker reuse for the betterment of society. PMHYH is leading the way
in the effort and is poised to conduct a prospective randomized, non-inferiority,
multicenter study to confirm the clinical efficacy and safety of pacemaker reuse,
for clinical and legal support.
PMID- 28515843
TI - Emerging concepts in alcoholic hepatitis.
AB - Severe alcoholic hepatitis is implicated as a costly, worldwide public health
issue with high morbidity and mortality. The one-month survival for severe
alcoholic hepatitis is low with mortality rates high as 30%-50%. Abstinence from
alcohol is the recommended first-line treatment. Although corticosteroids remain
as the current evidence based option for selected patients with discriminant
function > 32, improvement of short-term survival rate may be the only benefit.
Identification of individuals with risk factors for the development of severe
alcoholic hepatitis may provide insight to the diverse clinical spectrum and
prognosis of the disease. The understanding of the complex pathophysiologic
processes of alcoholic hepatitis is the key to elucidating new therapeutic
treatments. Newer research describes the use of gut microbiota modification,
immune modulation, stimulation of liver regeneration, caspase inhibitors,
farnesoid X receptors, and the extracorporeal liver assist device to aid in
hepatocellular recovery. Liver transplantation can be considered as the last
medical option for patients failing conventional medical interventions. Although
the preliminary data is promising in patients with low risk of recividism,
controversy remains due to organ scarcity. This review article comprehensively
summarizes the epidemiology, pathophysiology, risk factors, and prognostic
indicators of severe alcoholic hepatitis with a focus on the current and emerging
therapeutics.
PMID- 28515849
TI - Feature tracking cardiac magnetic resonance imaging: A review of a novel non
invasive cardiac imaging technique.
AB - Cardiovascular disease is a leading cause of morbidity and mortality globally.
Early diagnostic markers are gaining popularity for better patient care disease
outcomes. There is an increasing interest in noninvasive cardiac imaging
biomarkers to diagnose subclinical cardiac disease. Feature tracking cardiac
magnetic resonance imaging is a novel post-processing technique that is
increasingly being employed to assess global and regional myocardial function.
This technique has numerous applications in structural and functional
diagnostics. It has been validated in multiple studies, although there is still a
long way to go for it to become routine standard of care.
PMID- 28515850
TI - Dissection of Z-disc myopalladin gene network involved in the development of
restrictive cardiomyopathy using system genetics approach.
AB - AIM: To investigate the regulation of Myopalladin (Mypn) and identify its gene
network involved in restrictive cardiomyopathy (RCM). METHODS: Gene expression
values were measured in the heart of a large family of BXD recombinant inbred
(RI) mice derived from C57BL/6J and DBA/2J. The proteomics data were collected
from Mypn knock-in and knock-out mice. Expression quantitative trait locus (eQTL)
mapping methods and gene enrichment analysis were used to identify Mypn
regulation, gene pathway and co-expression networks. RESULTS: A wide range of
variation was found in expression of Mypn among BXD strains. We identified
upstream genetic loci at chromosome 1 and 5 that modulate the expression of Mypn.
Candidate genes within these loci include Ncoa2, Vcpip1, Sgk3, and Lgi2. We also
identified 15 sarcomeric genes interacting with Mypn and constructed the gene
network. Two novel members of this network (Syne1 and Myom1) have been confirmed
at the protein level. Several members in this network are already known to relate
to cardiomyopathy with some novel genes candidates that could be involved in RCM.
CONCLUSION: Using systematic genetics approach, we constructed Mypn co-expression
networks that define the biological process categories within which similarly
regulated genes function. Through this strategy we have found several novel genes
that interact with Mypn that may play an important role in the development of
RCM.
PMID- 28515852
TI - Bilateral vs unilateral internal mammary revascularization in patients with left
ventricular dysfunction.
AB - AIM: To investigate the survival benefit of bilateral internal mammary artery
(BIMA) grafts in patients with left ventricular dysfunction. METHODS: Between
1996 and 2009, we performed elective, isolated, primary, multiple cardiac
arterial bypass grafting in 430 consecutive patients with left ventricular
ejection fraction <= 40%. The early and long-term results were compared between
167 patients undergoing BIMA grafting and 263 patients using left internal
mammary artery (LIMA)-saphenous venous grafting (SVG). RESULTS: The mean age of
the overall population was 60.1 +/- 15 years. In-hospital mortality was not
different between the two groups (7.8% vs 10.3%, P = 0.49). Early postoperative
morbidity included myocardial infarction (4.2% vs 3.8%, P = 0.80), stroke (1.2%
vs 3.8%, P = 0.14), and mediastinitis (5.3% vs 2.3%, P = 0.11). At 8-year follow
up, Kaplan-Meier-estimated survival (74.2% vs 58.9%, P = 0.02) and Kaplan-Meier
estimated event-free survival (all cause deaths, myocardial infarction, stroke,
target vessel revascularization, heart failure) (61.7% and 41.1%, P < 0.01) were
significantly higher in the BIMA group compared with the LIMA-SVG group in
univariate analysis. The propensity score matching analysis confirmed that BIMA
grafting is a safe revascularization procedure but there was no long term
survival (P = 0.40) and event-free survival (P = 0.13) in comparison with LIMA
SVG use. CONCLUSION: Our longitudinal analysis suggests that BIMA grafting can be
performed with acceptable perioperative mortality in patients with left
ventricular dysfunction.
PMID- 28515851
TI - Blood conservation pediatric cardiac surgery in all ages and complexity levels.
AB - AIM: To demonstrate the feasibility of blood conservation methods and practice
across all ages and risk categories in congenital cardiac surgery. METHODS: We
retrospectively analyzed a collected database of 356 patients who underwent
cardiac surgery using cardiopulmonary bypass (CPB) from 2010-2015. The patients
were grouped into blood conservation (n = 138) and non-conservation (n = 218)
groups and sub-grouped based on their ages and procedural complexity scores.
RESULTS: There were no statistical differences in gender, weight, pre-operative
and pre-CPB hematocrit levels in both groups. Despite equivalent hematocrit
levels during and after CPB for both groups, there was significantly less
operative homologous blood utilized in blood conservation group across all ages
and complexity levels. CONCLUSION: Blood conservation surgery can be performed in
congenital patients needing cardiac surgery in all age groups and complexity
categories. The above findings in addition to attendant risks and side effects of
blood transfusion and the rising cost of safer blood products justify blood
conservation in congenital cardiac surgery.
PMID- 28515856
TI - Inter-ethnic marriages and severity of coronary artery disease: A multicenter
study of Arabian Gulf States.
AB - AIM: To assess the association of inter-ethnic vs intra-ethnic marriage with
severity of coronary artery disease (CAD) in men undergoing angiography. METHODS:
We conducted a prospective multicenter, multi-ethnic, cross sectional
observational study at five hospitals in Saudi Arabia and the United Arab
Emirates, in which we used logistic regression analysis with and without
adjustment for baseline differences. RESULTS: Data were collected for 1068
enrolled patients undergoing coronary angiography for clinical indications during
the period of April 1st, 2013 to March 30th, 2014. Ethnicities of spouses were
available only for male patients. Of those enrolled, 687 were married men and
constituted the cohort for the present analysis. Intra-ethnic marriages were
reported in 70% and inter-ethnic marriages in 30%. After adjusting for baseline
differences, inter-ethnic marriage was associated with lower odds of having
significant CAD [adjusted odds ratio 0.52 (95%CI: 0.33, 0.81)] or multi-vessel
disease (MVD) [adjusted odds ratio 0.57 (95%CI: 0.37, 0.86)]. The adjusted
association with left main disease showed a similar trend, but was not
statistically significant [adjusted odds ratio 0.74 (95%CI: 0.41, 1.32)]. The
association between inter-ethnic marriage and the presence of significant CAD and
MVD was not modified by number of concurrent wives (P interaction > 0.05 for
both). CONCLUSION: Among married men undergoing coronary angiography, inter
ethnic, as compared to intra-ethnic, marriage is associated with lower odds of
significant CAD and MVD.
PMID- 28515853
TI - QT prolongation is associated with increased mortality in end stage liver
disease.
AB - AIM: To determine the prevalence of QT prolongation in a large series of end
stage liver disease (ESLD) patients and its association to clinical variables and
mortality. METHODS: The QT interval was measured and corrected for heart rate for
each patient, with a prolonged QT cutoff defined as QT > 450 ms for males and QT
> 470 ms for females. Multiple clinical variables were evaluated including sex,
age, serum sodium, international normalized ratio, creatinine, total bilirubin,
beta-blocker use, Model for End-Stage Liver Disease (MELD), MELD-Na, and etiology
of liver disease. RESULTS: Among 406 ESLD patients analyzed, 207 (51.0%) had QT
prolongation. The only clinical variable associated with QT prolongation was male
gender (OR = 3.04, 95%CI: 2.01-4.60, P < 0.001). During the study period, 187
patients (46.1%) died. QT prolongation was a significant independent predictor of
mortality (OR = 1.69, 95%CI: 1.03-2.77, P = 0.039). In addition, mortality was
also associated with viral etiology of ESLD, elevated MELD score and its
components (P < 0.05 for all). No significant reversibility in the QT interval
was seen after liver transplantation. CONCLUSION: QT prolongation was commonly
encountered in an ESLD population, especially in males, and served as a strong
independent marker for increased mortality in ESLD patients.
PMID- 28515858
TI - Three-dimensional optical coherence tomography reconstruction of bifurcation
stenting using the Szabo anchor-wire technique.
AB - Ostial lesions present unique challenges for percutaneous coronary intervention
(PCI). These lesions are often more calcified, fibrotic, rigid, and more prone to
elastic recoil. Intervention on these lesions is associated with higher
procedural complications and higher rates of restenosis. Ostial lesions require
precise stent placement in the ostium with the absence of side branch compromise.
Accurate stent placement in the ostium without side branch compromise is
difficult to accomplish with angiography alone. The Szabo technique uses two
coronary guidewires for the correct placement in the aorto-ostial or bifurcation
lesion. One guidewire is passed through the final cell of the stent strut and
acts as the anchor wire. It helps to prevent migration of the stent beyond the
ostium and facilitates the precise stenting at the ostium. This technique has
several advantages including less reliance on angiography, lower rates of stent
malposition and lower rates of incomplete stent coverage. Potential disadvantages
include stent distortion and dislodgement from stent manipulation. We describe
two cases of successful PCI to bifurcation lesions using the Szabo technique and
confirmation of correct placement in the ostium with optical coherence
tomography.
PMID- 28515857
TI - Contrast use in relation to the arterial access site for percutaneous coronary
intervention: A comprehensive meta-analysis of randomized trials.
AB - AIM: To compare the amount of contrast used during percutaneous coronary
intervention (PCI) via trans-radial access (TRA) vs trans-femoral access (TFA).
METHODS: Scientific databases and websites were searched
for:randomizedcontrolledtrials (RCTs). Data were extracted by two independent
reviewers and was summarized as the weighted mean difference (WMD) of contrast
used with a 95%CI using a random-effects model. RESULTS: The meta-analysis
included 13 RCTs with a total of 3165 patients. There was no difference between
the two strategies in the amount of contrast used (WMD = - 0.65 mL, 95%CI: -10.94
9.46 mL; P = 0.901). CONCLUSION: This meta-analysis shows that in patients
undergoing PCI, the amount of contrast volume used was not different between TRA
and TFA.
PMID- 28515855
TI - Speckle tracking echocardiography to assess regional ventricular function in
patients with apical hypertrophic cardiomyopathy.
AB - AIM: To explore regional systolic strain of midwall and endocardial segments
using speckle tracking echocardiography in patients with apical hypertrophic
cardiomyopathy (HCM). METHODS: We prospectively assessed 20 patients (mean age 53
+/- 16 years, range: 18-81 years, 10 were male), with apical HCM. We measured
global longitudinal peak systolic strain (GLPSS) in the midwall and endocardium
of the left ventricle. RESULTS: The diastolic thickness of the 4 apical segments
was 16.25 +/- 2.75 mm. All patients had a normal global systolic function with a
fractional shortening of 50% +/- 8%. In spite of supernormal left ventricular
(LV) systolic function, midwall GLPSS was decreased in all patients, more in the
apical (-7.3% +/- -8.8%) than in basal segments (-15.5% +/- -6.93%), while
endocardial GLPPS was significantly greater and reached normal values (apical:
22.8% +/- -7.8%, basal: -17.9% +/- -7.5%). CONCLUSION: This study shows that two
dimensional strain was decreased mainly confined to the mesocardium, while
endocardium myocardial deformation was preserved in HCM and allowed to identify
subclinical LV dysfunction. This transmural heterogeneity in systolic strain had
not been previously described in HCM and could be explained by the distribution
of myofibrillar disarray in deep myocardial areas. The clinical application of
this novel finding may help further understanding of the pathophysiology of HCM.
PMID- 28515859
TI - Conservative management of aortic root rupture complicated with cardiac tamponade
following transcatheter aortic valve implantation.
AB - Aortic root rupture and cardiac tamponade during transcatheter aortic valve
implantation is a frightening complication with high mortality rate. A
conservative management of this complication could represent an initial strategy,
especially in high-risk patients, to avoid emergent cardiac surgery. This
conservative management includes: Immediate detection of pericardial effusion by
echocardiography, a fast instauration of pericardial drainage, auto-transfusion
and anticoagulation reversal. We describe two cases of patients who suffered this
complication and were treated successfully with this initial approach.
PMID- 28515854
TI - Determinants of percutaneous coronary intervention success in repeat chronic
total occlusion procedures following an initial failed attempt.
AB - AIM: To investigate the rates and determinants of success of repeat percutaneous
coronary intervention (PCI) following an initial failed attempt at recanalising
the chronic total occlusions (CTO) percutaneously. METHODS: In 445 consecutive
first attempt CTO-PCI procedures in our institution, procedural failure occurred
in 149 (33.5%). Sixty-four re-PCI procedures were performed in 58 patients (39%)
all had a single CTO. Procedural and outcome data in the re-PCI population was
entered into the institutional database. A retrospective analysis of clinical,
angiographic and procedural data was performed. RESULTS: Procedural success was
achieved in 41 (64%) procedures. Univariate analysis of clinical and angiographic
characteristics showed that re-PCI success was associated with intravascular
ultrasound (IVUS) guidance (19.5% vs 0%, P = 0.042), while failure was associated
with severe calcification (30.4% vs 9.7%, P = 0.047) and a JCTO score > 3 (56.5%
vs 17.1% P = 0.003). Following multiple regression analysis the degree of lesion
complexity (J-CTO score > 3), IVUS use, involvement of an experienced CTO
operator and LAD CTO location were significant predictors of successful re-PCI.
Overall the complication rate was low, with the only MACCE two periprocedural
MI's neither of which required intervention. CONCLUSION: Re-PCI substantially
increases the overall success rate of CTO revascularization. Predictors of re-PCI
success included the use of IVUS, the involvement of an experienced CTO operator
in the repeat attempt and the location of the CTO.
PMID- 28515860
TI - Cardiotoxicity occurred in aged C57BL/6nia mice given a formulation containing
poloxamer 407 hydrogel.
PMID- 28515861
TI - The emerging role of geropathology in preclinical aging studies.
PMID- 28515862
TI - Guidelines for collection and processing of lungs from aged mice for histological
studies.
AB - Pulmonary inflammation and the development of spontaneous lung tumors are
important age-related lesions in mice. Therefore, gross and histological
examination of the respiratory system is a critical component of geropathology
research studies for translating surrogate endpoints to clinical aging studies.
Collection, trimming, and processing of lung tissue from aged mice require a high
quality sequential process since aged mice are irreplaceable resource-intensive
animal models. This protocol provides a basic technique that provides excellent
sections for histological evaluation of the respiratory system of old mice
suitable for most research applications. The points of emphasis are infusing the
lungs at necropsy with formalin through the airways to prevent atelectasis
artifacts that can preclude accurate histological evaluation, and embedding of
anatomically oriented in toto lung lobes to allow for complete and thorough
evaluation of all lung regions.
PMID- 28515863
TI - Structural Segmentation of Toru Takemitsu's Piece, Itinerant, by Advanced Level
Music Graduate Students.
AB - This work attempts to study the way higher music graduate students segment a
contemporary music work, Itinerant, and to understand the influence of musical
feature on segmentation. It attempts to test the theory stating that saliences
contribute to organising the music surface. The 42 students listened to the work
several times and, in real time, they were requested to indicate the places on
the score where they perceived structural boundaries. This work is characterised
by its linearity, which could hinder identification of saliences and thereby, the
establishment of structural boundaries. The participants show stability in the
points of segmentation chosen. The results show significant coincidences among
the participants in strategic places of the work, which leads us to conclude, in
line with other researches, although in a work with different characteristics,
that listeners can find a structural organisation in contemporary music that
could allow them to understand it.
PMID- 28515864
TI - The Planispheric Optic Array.
AB - The "planispheric optic array" is a full-horizon Mercator projection of the optic
array. Such pictures of the environment are coming in common use with the
availability of cheap full-view cameras of reasonable quality. This introduces
the question of whether the public will actually profit from such pictorial
information in terms of an understanding of the spatial layout of the depicted
scene. Test images include four persons located at the corners of a square
centered at the camera. The persons point at each other in various combinations.
Participants in the experiment judge who is pointing at whom in a number of such
photographs. It is found that certain very systematic and huge errors are the
rule, indicating that naive viewers are quite unable to parse such planispheric
representations.
PMID- 28515865
TI - Innocent Body-Shadow Mimics Physical Body.
AB - The paradigm of the rubber hand illusion was applied to a shadow to determine
whether the body-shadow is a good candidate for the alternative belonging to our
body. Three kinds of shadows, a physical hand, a hand-shaped cloth, and a
rectangle cloth, were tested for this purpose. The questionnaire results showed
that both anatomical similarity and visuo-proprioception correlation were
effective in enhancing illusory ownership of the shadow. According to the
proprioceptive drift measurement, whether the shadow purely originated from the
physical body was a critical factor in yielding the significantly positive drift.
Thus, results demonstrated that the shadow can distort illusory ownership with
the rubber hand illusion paradigm, but the proprioception was clearly distorted
only when the body-shadow was purely applied. This implies the presence of
special cognitive processing to discriminate the self-body shadow from the
others.
PMID- 28515866
TI - Effect of Different Display Types on Vection and Its Interaction With Motion
Direction and Field Dependence.
AB - Illusory self-motion (vection) can be generated by visual stimulation. The
purpose of the present study was to compare behavioral vection measures including
intensity ratings, duration, and onset time across different visual display
types. Participants were exposed to a pattern of alternating black-and-white
horizontal or vertical bars that moved either in vertical or horizontal
direction, respectively. Stimuli were presented on four types of displays in
randomized order: (a) large field of view dome projection, (b) combination of
three computer screens, (c) single computer screen, (d) large field of view flat
projection screen. A Computer Rod and Frame Test was used to measure field
dependence, a cognitive style indicating the person's tendency to rely on
external cues (i.e., field dependent) or internal cues (i.e., field independent)
with respect to the perception of one's body position in space. Results revealed
that all four displays successfully generated at least moderately strong vection.
However, shortest vection onset, longest vection duration, and strongest vection
intensity showed for the dome projection and the combination of three screens.
This effect was further pronounced in field independent participants, indicating
that field dependence can alter vection.
PMID- 28515867
TI - The evolution of the major histocompatibility complex in upstream versus
downstream river populations of the longnose dace.
AB - Populations in upstream versus downstream river locations can be exposed to
vastly different environmental and ecological conditions and can thus harbor
different genetic resources due to selection and neutral processes. An
interesting question is how upstream-downstream directionality in rivers affects
the evolution of immune response genes. We used next-generation amplicon
sequencing to identify eight alleles of the major histocompatibility complex
(MHC) class II beta exon 2 in the cyprinid longnose dace (Rhinichthys cataractae)
from three rivers in Alberta, upstream and downstream of municipal and
agricultural areas along contaminant gradients. We used these data to test for
directional and balancing selection on the MHC. We also genotyped microsatellite
loci to examine neutral population processes in this system. We found evidence
for balancing selection on the MHC in the form of increased nonsynonymous
variation relative to neutral expectations, and selection occurred at more amino
acid residues upstream than downstream in two rivers. We found this pattern
despite no population structure or isolation by distance, based on microsatellite
data, at these sites. Overall, our results suggest that MHC evolution is driven
by upstream-downstream directionality in fish inhabiting this system.
PMID- 28515869
TI - Implications of guppy (Poecilia reticulata) life-history phenotype for mosquito
control.
AB - Guppies (Poecilia reticulata) are frequently introduced to both natural and
artificial water bodies as a mosquito control. Laboratory studies have
demonstrated that guppies can consume large numbers of larval mosquitoes. Our
study investigates how intraspecific variability in guppy phenotype affects their
importance as a mosquito biocontrol and how habitat conditions (natural ponds vs.
water storage containers) may influence insect biomass and guppy feeding. Using a
blocked experimental design, we established stream-side mesocosm ponds with half
receiving gravel substrate to simulate pond-bottom habitat. To provide realistic
diet choices and insect abundances, we allowed the mesocosms to colonize
naturally with aquatic insect larvae for 1 month before introducing guppies. We
tested two distinct guppy phenotypes (from high- and low-predation streams)
alongside fish-free controls. After 1 month, we measured insect biomass in the
mesocosms and examined guppy gut contents to document direct predation. While
overall insect biomass was not significantly different across the three fish
treatments, we observed a significant reduction in mosquito biomass in fish
treatments compared to fish-free controls, as well as intraspecific differences
in feeding. Overall insect biomass was significantly higher in mesocosms without
gravel, while habitat condition had no effect on mosquito biomass. As guppy
phenotype responds to changes in their environments, it is an important
consideration for biocontrol policy to anticipate potential ecosystem effects. We
close by relating our findings to other studies and by discussing the
implications and potential risks of using guppies to control mosquitoes.
PMID- 28515868
TI - Postglacial recolonization shaped the genetic diversity of the winter moth
(Operophtera brumata) in Europe.
AB - Changes in climate conditions, particularly during the Quaternary climatic
oscillations, have long been recognized to be important for shaping patterns of
species diversity. For species residing in the western Palearctic, two commonly
observed genetic patterns resulting from these cycles are as follows: (1) that
the numbers and distributions of genetic lineages correspond with the use of
geographically distinct glacial refugia and (2) that southern populations are
generally more diverse than northern populations (the "southern richness,
northern purity" paradigm). To determine whether these patterns hold true for the
widespread pest species the winter moth (Operophtera brumata), we genotyped 699
individual winter moths collected from 15 Eurasian countries with 24 polymorphic
microsatellite loci. We find strong evidence for the presence of two major
genetic clusters that diverged ~18 to ~22 ka, with evidence that secondary
contact (i.e., hybridization) resumed ~ 5 ka along a well-established hybrid zone
in Central Europe. This pattern supports the hypothesis that contemporary
populations descend from populations that resided in distinct glacial refugia.
However, unlike many previous studies of postglacial recolonization, we found no
evidence for the "southern richness, northern purity" paradigm. We also find
evidence for ongoing gene flow between populations in adjacent Eurasian
countries, suggesting that long-distance dispersal plays an important part in
shaping winter moth genetic diversity. In addition, we find that this gene flow
is predominantly in a west-to-east direction, suggesting that recently debated
reports of cyclical outbreaks of winter moth spreading from east to west across
Europe are not the result of dispersal.
PMID- 28515870
TI - Behavioral responses to encounter of fishing boats in wandering albatrosses.
AB - Animals are attracted to human food subsidies worldwide. The behavioral response
of individuals to these resources is rarely described in detail, beyond chances
of encounters. Seabirds for instance scavenge in large numbers at fishing boats,
triggering crucial conservation issues, but how the response to boats varies
across encounters is poorly known. Here we examine the behavioral response of
wandering albatrosses (Diomedea exulans), equipped with GPS tags, to longline
fishing boats operating near their colony for which we had access to vessel
monitoring system data. We distinguish between encounters (flying within 30 km of
a boat) and attendance behavior (sitting on the sea within 3 km of a boat), and
examine factors affecting each. In particular, we test hypotheses that the
response to encountered boats should vary with sex and age in this long-lived
dimorphic species. Among the 60% trips that encountered boats at least once, 80%
of them contained attendance (but attendance followed only 60% of each single
encounter). Birds were more attracted and remained attending longer when boats
were hauling lines, despite the measures enforced by this fleet to limit food
availability during operations. Sex and age of birds had low influence on the
response to boats, except the year when fewer boats came fishing in the area, and
younger birds were attending further from boats compared to older birds. Net mass
gain of birds was similar across sex and not affected by time spent attending
boats. Our results indicate albatrosses extensively attend this fishery, with no
clear advantages, questioning impacts on foraging time budgets. Factors
responsible for sex foraging segregation at larger scale seem not to operate at
this fleet near the colony and are not consistent with predictions of optimal
foraging theory on potential individual dominance asymmetries. This approach
complements studies of large-scale overlap of animals with human subsidies.
PMID- 28515871
TI - Wolf in sheep's clothing: Model misspecification undermines tests of the neutral
theory for life histories.
AB - Understanding the processes behind change in reproductive state along life
history trajectories is a salient research program in evolutionary ecology. Two
processes, state dependence and heterogeneity, can drive the dynamics of change
among states. Both processes can operate simultaneously, begging the difficult
question of how to tease them apart in practice. The Neutral Theory for Life
Histories (NTLH) holds that the bulk of variations in life-history trajectories
is due to state dependence and is hence neutral: Once previous (breeding) state
is taken into account, variations are mostly random. Lifetime reproductive
success (LRS), the number of descendants produced over an individual's
reproductive life span, has been used to infer support for NTLH in natura.
Support stemmed from accurate prediction of the population-level distribution of
LRS with parameters estimated from a state dependence model. We show with Monte
Carlo simulations that the current reliance of NTLH on LRS prediction in a null
hypothesis framework easily leads to selecting a misspecified model, biased
estimates and flawed inferences. Support for the NTLH can be spurious because of
a systematic positive bias in estimated state dependence when heterogeneity is
present in the data but ignored in the analysis. This bias can lead to spurious
positive covariance between fitness components when there is in fact an
underlying trade-off. Furthermore, neutrality implied by NTLH needs a
clarification because of a probable disjunction between its common understanding
by evolutionary ecologists and its translation into statistical models of life
history trajectories. Irrespective of what neutrality entails, testing hypotheses
about the dynamics of change among states in life histories requires a multimodel
framework because state dependence and heterogeneity can easily be mistaken for
each other.
PMID- 28515872
TI - Increasing copper alters cellular elemental composition (Mo and P) of marine
diatom.
AB - The elemental composition (surface adsorbed and internalized fraction of Cu, Mo
and P) in marine phytoplankton was first examined in cultures of the diatom
Phaeodactylum tricornutum which were exposed to various levels of Cu
concentrations ranging from 0.25 to 16 MUmol/L with equivalent free [Cu2+]
concentrations of 0.4-26 nmol/L. We observed an acceleration of algal growth
rates (20-40%) with increasing ambient Cu levels, as well as slightly increased
levels of internalized Cu in cells (2-13 * 10-18 mol/cell) although cellular Cu
mostly accumulated onto the cell surface (>50% of the total: intracellular +
surface adsorbed). In particular, we documented for the first time that the
elemental composition (Mo and P) in algal cells varies dynamically in response to
increased Cu levels: (1) Cellular P, predominantly in the intracellular
compartment (>95%), shows with a net consumption as indicated by a gradual
decrease with increasing [Cu2+] (120->50 * 10-15 mol P/cell) probably due to the
fact that P, a backbone bioelement, is largely required in forming biological
compartments such as cell membranes; and (2) cellular Mo, predominantly
encountered in the intracellular compartment, showed up to tenfold increase in
concentration in the cultures exposed to Cu, with a peak accumulation of 1.1 * 10
18 mol Mo/cell occurring in the culture exposed to [Cu2+] at 3.7 nmol/L. Such a
net cellular Mo accumulation suggests that Mo might be specifically required in
biological processes, probably playing a counteracting role against Cu.
PMID- 28515873
TI - Brain morphology of the threespine stickleback (Gasterosteus aculeatus) varies
inconsistently with respect to habitat complexity: A test of the Clever Foraging
Hypothesis.
AB - The Clever Foraging Hypothesis asserts that organisms living in a more spatially
complex environment will have a greater neurological capacity for cognitive
processes related to spatial memory, navigation, and foraging. Because the
telencephalon is often associated with spatial memory and navigation tasks, this
hypothesis predicts a positive association between telencephalon size and
environmental complexity. The association between habitat complexity and brain
size has been supported by comparative studies across multiple species but has
not been widely studied at the within-species level. We tested for covariation
between environmental complexity and neuroanatomy of threespine stickleback
(Gasterosteus aculeatus) collected from 15 pairs of lakes and their parapatric
streams on Vancouver Island. In most pairs, neuroanatomy differed between the
adjoining lake and stream populations. However, the magnitude and direction of
this difference were inconsistent between watersheds and did not covary strongly
with measures of within-site environmental heterogeneity. Overall, we find weak
support for the Clever Foraging Hypothesis in our study.
PMID- 28515874
TI - Universal expressions of population change by the Price equation: Natural
selection, information, and maximum entropy production.
AB - The Price equation shows the unity between the fundamental expressions of change
in biology, in information and entropy descriptions of populations, and in
aspects of thermodynamics. The Price equation partitions the change in the
average value of a metric between two populations. A population may be composed
of organisms or particles or any members of a set to which we can assign
probabilities. A metric may be biological fitness or physical energy or the
output of an arbitrarily complicated function that assigns quantitative values to
members of the population. The first part of the Price equation describes how
directly applied forces change the probabilities assigned to members of the
population when holding constant the metrical values of the members-a fixed
metrical frame of reference. The second part describes how the metrical values
change, altering the metrical frame of reference. In canonical examples, the
direct forces balance the changing metrical frame of reference, leaving the
average or total metrical values unchanged. In biology, relative reproductive
success (fitness) remains invariant as a simple consequence of the conservation
of total probability. In physics, systems often conserve total energy.
Nonconservative metrics can be described by starting with conserved metrics, and
then studying how coordinate transformations between conserved and nonconserved
metrics alter the geometry of the dynamics and the aggregate values of
populations. From this abstract perspective, key results from different subjects
appear more simply as universal geometric principles for the dynamics of
populations subject to the constraints of particular conserved quantities.
PMID- 28515875
TI - Seasonal abundance and habitat use of bird species in and around Wondo Genet
Forest, south-central Ethiopia.
AB - The habitat use and seasonal migratory pattern of birds in Ethiopia is less
explored as compared to diversity studies. To this end, this study aimed at
investigating the patterns of distribution related to seasonality and the effect
of habitat characteristics (elevation, slope, and average vegetation height) on
habitat use of birds of Wondo Genet Forest Patch. A stratified random sampling
design was used to assess the avian fauna across the four dominant habitat types
found in the study area: natural forest, wooded grassland, grassland, and
agroforestry land. A point transect count was employed to investigate avian
species richness and abundance per habitat type per season. Ancillary data, such
as elevation above sea level, latitude and longitude, average vegetation height,
and percent slope inclination, were recorded with a GPS and clinometers per plot.
A total of 33 migratory bird species were recorded from the area, of which 20
species were northern (Palearctic) migrants while 13 were inter-African migrants.
There was a significant difference in the mean abundance of migratory bird
species between dry and wet seasons (t = 2.13, p = .038, df = 44). The variation
in mean abundance per plot between the dry and wet seasons in the grassland
habitat was significant (t = 2.35, p = .051, df = 7). In most habitat types
during both dry and wet seasons, omnivore birds were the most abundant. While
slope was a good predictor for bird species abundance in the dry season, altitude
and average vegetation height accounted more in the wet season. The patch of
forest and its surrounding is an important bird area for migratory, endemic, and
global threatened species. Hence, it is conservation priority area, and the study
suggests that conservation coupled with ecotourism development is needed for its
sustainability.
PMID- 28515876
TI - Population genomics reveals a candidate gene involved in bumble bee pigmentation.
AB - Variation in bumble bee color patterns is well-documented within and between
species. Identifying the genetic mechanisms underlying such variation may be
useful in revealing evolutionary forces shaping rapid phenotypic diversification.
The widespread North American species Bombus bifarius exhibits regional variation
in abdominal color forms, ranging from red-banded to black-banded phenotypes and
including geographically and phenotypically intermediate forms. Identifying
genomic regions linked to this variation has been complicated by strong, near
species level, genome-wide differentiation between red- and black-banded forms.
Here, we instead focus on the closely related black-banded and intermediate forms
that both belong to the subspecies B. bifarius nearcticus. We analyze an RNA
sequencing (RNAseq) data set and identify a cluster of single nucleotide
polymorphisms (SNPs) within one gene, Xanthine dehydrogenase/oxidase-like, that
exhibit highly unusual differentiation compared to the rest of the sequenced
genome. Homologs of this gene contribute to pigmentation in other insects, and
results thus represent a strong candidate for investigating the genetic basis of
pigment variation in B. bifarius and other bumble bee mimicry complexes.
PMID- 28515877
TI - Sex-specific repeatabilities and effects of relatedness and mating status on
copulation duration in an acridid grasshopper.
AB - In species with direct sperm transfer, copulation duration is a crucial trait
that may affect male and female reproductive success and that may vary with the
quality of the mating partner. Furthermore, traits such as copulation duration
represent the outcome of behavioral interactions between the sexes, for which it
is important-but often difficult-to determine which sex is in phenotypic control.
Using a double-mating protocol, we compared copulation durations between (1)
virgin and nonvirgin and (2) sibling and nonsibling mating pairs in rufous
grasshoppers Gomphocerippus rufus. Nonvirgin copulations took on average
approximately 30% longer than virgin copulations, whereas relatedness of mating
partners was not a significant predictor of copulation duration. Longer nonvirgin
copulations may represent a male adaptation to sperm competition if longer
copulations allow more sperm to be transferred or function as postinsemination
mate guarding. The absence of differences between pairs with different degrees of
relatedness suggests no precopulatory or preinsemination inbreeding avoidance
mechanism has evolved in this species, perhaps because there is no inbreeding
depression in this species, or because inbreeding avoidance occurs after
copulation. Controlling for the effects of male and female mating status (virgin
vs. nonvirgin) and relatedness (sibling vs. nonsibling), we found significant
repeatabilities (R) in copulation duration for males (R = 0.33; 95% CI: 0.09
0.55) but not for females (R = 0.09; 95% CI: 0.00-0.30). Thus, copulation
durations of males more strongly represent a nontransient trait expressed in a
consistent manner with different mating partners, suggesting that some aspect of
the male phenotype may determine copulation duration in this species. However,
overlapping confidence intervals for our sex-specific repeatability estimates
indicate that higher sampling effort is required for conclusive evidence.
PMID- 28515878
TI - A multispecies dependent double-observer model: A new method for estimating
multispecies abundance.
AB - Conservation of biological communities requires accurate estimates of abundance
for multiple species. Recent advances in estimating abundance of multiple
species, such as Bayesian multispecies N-mixture models, account for multiple
sources of variation, including detection error. However, false-positive errors
(misidentification or double counts), which are prevalent in multispecies data
sets, remain largely unaddressed. The dependent-double observer (DDO) method is
an emerging method that both accounts for detection error and is suggested to
reduce the occurrence of false positives because it relies on two observers
working collaboratively to identify individuals. To date, the DDO method has not
been combined with advantages of multispecies N-mixture models. Here, we derive
an extension of a multispecies N-mixture model using the DDO survey method to
create a multispecies dependent double-observer abundance model (MDAM). The MDAM
uses a hierarchical framework to account for biological and observational
processes in a statistically consistent framework while using the accurate
observation data from the DDO survey method. We demonstrate that the MDAM
accurately estimates abundance of multiple species with simulated and real
multispecies data sets. Simulations showed that the model provides both precise
and accurate abundance estimates, with average credible interval coverage across
100 repeated simulations of 94.5% for abundance estimates and 92.5% for detection
estimates. In addition, 92.2% of abundance estimates had a mean absolute percent
error between 0% and 20%, with a mean of 7.7%. We present the MDAM as an
important step forward in expanding the applicability of the DDO method to a
multispecies setting. Previous implementation of the DDO method suggests the MDAM
can be applied to a broad array of biological communities. We suggest that
researchers interested in assessing biological communities consider the MDAM as a
tool for deriving accurate, multispecies abundance estimates.
PMID- 28515879
TI - Sexual signals reflect telomere dynamics in a wild bird.
AB - Telomere dynamics in natural populations have been linked to survival,
reproduction, and energetic investment. Given their putative role in mediating
life-history trade-offs, telomeres are also a likely candidate for maintaining
honesty in sexually selected signals; few studies to date, however, have
demonstrated a correlation between sexual signals and telomere dynamics. Here, we
show that plumage coloration in male common yellowthroats (Geothlypis trichas) is
correlated with both relative telomere length and with the rate of telomere loss
between years. Elevated antioxidant capacity is also associated with reduced
telomere loss, but only among older males. Previous work in this population has
demonstrated that males with brighter plumage are in better condition, have
higher reproductive success, and are more likely to survive over winter. Thus,
the signal attribute associated with mate choice in this system also conveys
reliable information about telomere dynamics. At present, it is unclear whether
telomere maintenance plays a causal role in maintaining signal honesty or whether
the correlation arises due to underlying variation in individual resources or
genotypes. We suggest that subsequent work should consider the possibility that
fundamental trade-offs between signal investment and cell-level processes that
influence aging and reproductive senescence may provide a foundation for
understanding the maintenance of sexual signal honesty.
PMID- 28515880
TI - Resistance and resilience of root fungal communities to water limitation in a
temperate agroecosystem.
AB - Understanding crop resilience to environmental stress is critical in predicting
the consequences of global climate change for agricultural systems worldwide, but
to date studies addressing crop resiliency have focused primarily on plant
physiological and molecular responses. Arbuscular mycorrhizal fungi (AMF) form
mutualisms with many crop species, and these relationships are key in mitigating
the effects of abiotic stress in many agricultural systems. However, to date
there is little research examining whether (1) fungal community structure in
agroecosystems is resistant to changing environmental conditions, specifically
water limitation and (2) resilience of fungal community structure is moderated by
agricultural management systems, namely the integration of trees into cropping
systems. Here, we address these uncertainties through a rainfall reduction field
experiment that manipulated short-term water availability in a soybean-based
(Glycine max L. Merr.) agroforest in Southern Ontario, Canada. We employed
terminal restriction fragment length polymorphism analysis to determine the
molecular diversity of both general fungal and AMF communities in soybean roots
under no stress, stress (rainfall shelters added), and poststress (rainfall
shelters removed). We found that general fungal and AMF communities sampled from
soybean roots were resistant to rainfall reduction in a monoculture, but not in
an agroforest. While AMF communities were unchanged after stress removal, general
fungal communities were significantly different poststress in the agroforest,
indicating a capacity for resiliency. Our study indicates that generalist fungi
and AMF are responsive to changes in environmental conditions and that
agroecosystem management plays a key role in the resistance and resilience of
fungal communities to water limitation.
PMID- 28515883
TI - Correlating species and spectral diversities using hyperspectral remote sensing
in early-successional fields.
AB - Advances in remote sensing technology can help estimate biodiversity at large
spatial extents. To assess whether we could use hyperspectral visible near
infrared (VNIR) spectra to estimate species diversity, we examined the
correlations between species diversity and spectral diversity in early
successional abandoned agricultural fields in the Ridge and Valley ecoregion of
north-central Virginia at the Blandy Experimental Farm. We established plant
community plots and collected vegetation surveys and ground-level hyperspectral
data from 350 to 1,025 nm wavelengths. We related spectral diversity (standard
deviations across spectra) with species diversity (Shannon-Weiner index) and
evaluated whether these correlations differed among spectral regions throughout
the visible and near-infrared wavelength regions, and across different spectral
transformation techniques. We found positive correlations in the visible regions
using band depth data, positive correlations in the near-infrared region using
first derivatives of spectra, and weak to no correlations in the red-edge region
using either of the two spectral transformation techniques. To investigate the
role of pigment variability in these correlations, we estimated chlorophyll,
carotenoid, and anthocyanin concentrations of five dominant species in the plots
using spectral vegetation indices. Although interspecific variability in pigment
levels exceeded intraspecific variability, chlorophyll was more varied within
species than carotenoids and anthocyanins, contributing to the lack of
correlation between species diversity and spectral diversity in the red-edge
region. Interspecific differences in pigment levels, however, made it possible to
differentiate these species remotely, contributing to the species-spectral
diversity correlations. VNIR spectra can be used to estimate species diversity,
but the relationships depend on the spectral region examined and the spectral
transformation technique used.
PMID- 28515881
TI - Effect of Bursaphelenchus xylophilus infection on leaf photosynthetic
characteristics and resource-use efficiency of Pinus massoniana.
AB - Pine wilt disease (PWD) is considered as the most destructive forest-invasive
alien species in China. We measured gas exchange parameters and foliar carbon
isotope ratios (delta13C) of different infection phases of Masson pine in order
to investigate the effect of Bursaphelenchus xylophilus infection on
photosynthetic responses and resource-use efficiency. The results showed that net
photosynthetic rate (Pn), transpiration rate (T), stomatal conductance (gs), and
internal CO 2 concentrations (Ci) decreased in the infested trees at
photosynthetic photon flux density (PPFD) levels from 0 to 2,000 MUmol m-2 s-1
compared with controls. The maximum net photosynthetic rate (Pmax) was
significantly declined in the infected trees than in controls (p < .05). There
also exist significant differences in dark respiration rate (Rd) among different
infection phases (p < .05), but the value is highest in the middle infection
phase, followed by the control and then the terminal infection phase. This
indicates that Pinus massoniana plants need to consume more photosynthetic
products during the middle infection phase in order to defend against pine sawyer
beetle feeding and PWD infection. Isotopic analysis revealed a significant
decrease of the foliar delta13C (p < .05), as much as 2.50/00 lower in the
infected trees. The mean leaf N content was about 12.94% less in the middle
infection phase and 27.06% less in the terminal infection phase, causing a
significant increase of the foliar C:N ratio in infested trees. Both of the net
photosynthetic rates and foliar delta13C were linearly correlated with the foliar
N content. We also found a significant decrease (p < .05) of resource-use
efficiency in PWD-induced P. massoniana plants, which can be attributed to the
closure of stomatal pores and the inactivation or loss of both Rubisco and other
key Calvin cycle enzymes. This study highlights the impact of photosynthetic
characteristics, foliar carbon isotope ratios, and resource-use efficiency of PWD
induced trees, which can help identify PWD infestations at the photosynthetic and
physiological levels so as to better facilitate management actions.
PMID- 28515882
TI - Different categories of biodiversity explain productivity variation after
fertilization in a Tibetan alpine meadow community.
AB - The relationship between productivity and biodiversity has long been an important
issue in ecological research. However, in recent decades, most ecologists have
primarily focused on species diversity while paying little attention to
functional diversity and phylogenetic diversity (PD), especially in alpine meadow
communities following fertilization. In this study, a fertilization experiment
involving the addition of nitrogen, phosphorus, and a mixture of both was
implemented in an alpine meadow on the Tibetan Plateau. Species diversity,
functional diversity, and PD were measured, and the responses of these parameters
to the variation in productivity were analyzed. We found that the productivity of
alpine plant communities was colimited by N and P, with N being the principal and
P being the secondary limiting nutrient. Our results supported the prediction of
both the mass ratio hypothesis and niche complementarity hypothesis in fertilized
communities, but these hypotheses were not mutually exclusive. The combination of
different aspects of biodiversity not only provides a crucial tool to explain the
variation in productivity and to understand the underlying mechanisms but also
plays an important role in predicting the variation in productivity of alpine
meadow communities, which are sensitive to nutrient enrichment in the context of
global change.
PMID- 28515885
TI - Evaluating morphometric and metabolic markers of body condition in a small
cetacean, the harbor porpoise (Phocoena phocoena).
AB - Mammalian body condition is an important individual fitness metric as it affects
both survival and reproductive success. The ability to accurately measure
condition has key implications for predicting individual and population health,
and therefore monitoring the population-level effects of changing environments.
No consensus currently exists on the best measure to quantitatively estimate body
condition in many species, including cetaceans. Here, two measures of body
condition were investigated in the harbor porpoise (Phocoena phocoena). First,
the most informative morphometric body condition index was identified. The
mass/length2 ratio was the most appropriate morphometric index of 10 indices
tested, explaining 50% of the variation in condition in stranded, male porpoises
with different causes of death and across age classes (n = 291). Mass/length2 was
then used to evaluate a second measure, blubber cortisol concentration, as a
metabolic condition marker. Cortisol is the main glucocorticoid hormone involved
in the regulation of lipolysis and overall energy balance in mammals, and
concentrations could provide information on physiological state. Blubber cortisol
concentrations did not significantly vary around the girth (n = 20), but there
was significant vertical stratification through the blubber depth with highest
concentrations in the innermost layer. Concentrations in the dorsal, outermost
layer were representative of concentrations through the full blubber depth,
showed variation by sex and age class, and were negatively correlated with
mass/length2. Using this species as a model for live cetaceans from which
standard morphometric measurements cannot be taken, but from which blubber biopsy
samples are routinely collected, cortisol concentrations in the dorsal, outermost
blubber layer could potentially be used as a biomarker of condition in free
ranging animals.
PMID- 28515884
TI - Cooperative breeding shapes post-fledging survival in an Afrotropical forest
bird.
AB - For avian group living to be evolutionary stable, multiple fitness benefits are
expected. Yet, the difficulty of tracking fledglings, and thus estimating their
survival rates, limits our knowledge on how such benefits may manifest
postfledging. We radio-tagged breeding females of the Afrotropical cooperatively
breeding Placid greenbul (Phyllastrephus placidus) during nesting. Tracking these
females after fledging permitted us to locate juvenile birds, their parents, and
any helpers present and to build individual fledgling resighting datasets without
incurring mortality costs or causing premature fledging due to handling or
transmitter effects. A Bayesian framework was used to infer age-specific
mortality rates in relation to group size, fledging date, maternal condition, and
nestling condition. Postfledging survival was positively related to group size,
with fledglings raised in groups with four helpers showing nearly 30% higher
survival until independence compared with pair-only offspring, independent of
fledging date, maternal condition or nestling condition. Our results demonstrate
the importance of studying the early dependency period just after fledging when
assessing presumed benefits of cooperative breeding. While studying small, mobile
organisms after they leave the nest remains highly challenging, we argue that the
telemetric approach proposed here may be a broadly applicable method to obtain
unbiased estimates of postfledging survival.
PMID- 28515886
TI - Aquatic microfauna alter larval food resources and affect development and biomass
of West Nile and Saint Louis encephalitis vector Culex nigripalpus (Diptera:
Culicidae).
AB - Ciliate protists and rotifers are ubiquitous in aquatic habitats and can comprise
a significant portion of the microbial food resources available to larval
mosquitoes, often showing substantial declines in abundance in the presence of
mosquito larvae. This top-down regulation of protists is reported to be strong
for mosquitoes inhabiting small aquatic containers such as pitcher plants or tree
holes, but the nature of these interactions with larval mosquitoes developing in
other aquatic habitats is poorly understood. We examined the effects of these two
microbial groups on lower trophic level microbial food resources, such as
bacteria, small flagellates, and organic particles, in the water column, and on
Culex larval development and adult production. In three independent laboratory
experiments using two microeukaryote species (one ciliate protist and one
rotifer) acquired from field larval mosquito habitats and cultured in the
laboratory, we determined the effects of Culex nigripalpus larval grazing on
water column microbial dynamics, while simultaneously monitoring larval growth
and development. The results revealed previously unknown interactions that were
different from the top-down regulation of microbial groups by mosquito larvae in
other systems. Both ciliates and rotifers, singly or in combination, altered
other microbial populations and inhibited mosquito growth. It is likely that
these microeukaryotes, instead of serving as food resources, competed with early
instar mosquito larvae for microbes such as small flagellates and bacteria in a
density-dependent manner. These findings help our understanding of the basic
larval biology of Culex mosquitoes, variation in mosquito production among
various larval habitats, and may have implications for existing vector control
strategies and for developing novel microbial-based control methods.
PMID- 28515888
TI - Unpacking brown food-webs: Animal trophic identity reflects rampant microbivory.
AB - Detritivory is the dominant trophic paradigm in most terrestrial, aquatic, and
marine ecosystems, yet accurate measurement of consumer trophic position within
detrital (="brown") food webs has remained unresolved. Measurement of detritivore
trophic position is complicated by the fact that detritus is suffused with
microbes, creating a detrital complex of living and nonliving biomass. Given that
microbes and metazoans are trophic analogues of each other, animals feeding on
detrital complexes are ingesting other detritivores (microbes), which should
elevate metazoan trophic position and should be rampant within brown food webs.
We tested these hypotheses using isotopic (15N) analyses of amino acids extracted
from wild and laboratory-cultured consumers. Vertebrate (fish) and invertebrate
detritivores (beetles and moths) were reared on detritus, with and without
microbial colonization. In the field, detritivorous animal specimens were
collected and analyzed to compare trophic identities among laboratory-reared and
free-roaming detritivores. When colonized by bacteria or fungi, the trophic
positions of detrital complexes increased significantly over time. The magnitude
of trophic inflation was mediated by the extent of microbial consumption of
detrital substrates. When detrital complexes were fed to vertebrate and
invertebrate animals, the consumers registered similar degrees of trophic
inflation, albeit one trophic level higher than their diets. The wild-collected
detritivore fauna in our study exhibited significantly elevated trophic
positions. Our findings suggest that the trophic positions of detrital complexes
rise predictably as microbes convert nonliving organic matter into living
microbial biomass. Animals consuming such detrital complexes exhibit similar
trophic inflation, directly attributable to the assimilation of microbe-derived
amino acids. Our data demonstrate that detritivorous microbes elevate metazoan
trophic position, suggesting that detritivory among animals is, functionally,
omnivory. By quantifying the impacts of microbivory on the trophic positions of
detritivorous animals and then tracking how these effects propagate "up" food
chains, we reveal the degree to which microbes influence consumer groups within
trophic hierarchies. The trophic inflation observed among our field-collected
fauna further suggests that microbial proteins represent an immense contribution
to metazoan biomass. Collectively, these findings provide an empirical basis to
interpret detritivore trophic identity, and further illuminate the magnitude of
microbial contributions to food webs.
PMID- 28515887
TI - Bottom-up and top-down effects of tree species diversity on leaf insect
herbivory.
AB - The diversity of plant neighbors commonly results in direct, bottom-up effects on
herbivore ability to locate their host, and in indirect effects on herbivores
involving changes in plant traits and a top-down control by their enemies. Yet,
the relative contribution of bottom-up and top-down forces remains poorly
understood. We also lack knowledge on the effect of abiotic constraints such as
summer drought on the strength and direction of these effects. We measured leaf
damage on pedunculate oak (Quercus robur), alone or associated with birch, pine
or both in a long-term tree diversity experiment (ORPHEE), where half of the
plots were irrigated while the other half remained without irrigation and
received only rainfall. We tested three mechanisms likely to explain the effects
of oak neighbors on herbivory: (1) Direct bottom-up effects of heterospecific
neighbors on oak accessibility to herbivores, (2) indirect bottom-up effects of
neighbors on the expression of leaf traits, and (3) top-down control of
herbivores by predators. Insect herbivory increased during the growth season but
was independent of neighbor identity and irrigation. Specific leaf area, leaf
toughness, and thickness varied with neighbor identity while leaf dry matter
content or C:N ratio did not. When summarized in a principal component analysis
(PCA), neighbor identity explained 87% of variability in leaf traits. PCA axes
partially predicted herbivory. Despite greater rates of attack on dummy
caterpillars in irrigated plots, avian predation, and insect herbivory remained
unrelated. Our study suggests that neighbor identity can indirectly influence
insect herbivory in mixed forests by modifying leaf traits. However, we found
only partial evidence for these trait-mediated effects and suggest that more
attention should be paid to some unmeasured plant traits such as secondary
metabolites, including volatile organic compounds, to better anticipate the
effects of climate change on plant-insect interactions in the future.
PMID- 28515889
TI - Phenotypic plasticity in female mate choice behavior is mediated by an
interaction of direct and indirect genetic effects in Drosophila melanogaster.
AB - Female mate choice is a complex decision-making process that involves many
context-dependent factors. In Drosophila melanogaster, a model species for the
study of sexual selection, indirect genetic effects (IGEs) of general social
interactions can influence female mate choice behaviors, but the potential
impacts of IGEs associated with mating experiences are poorly understood. Here,
we examined whether the IGEs associated with a previous mating experience had an
effect on subsequent female mate choice behaviors and quantified the degree of
additive genetic variation associated with this effect. Females from 21 different
genetic backgrounds were housed with males from one of two distinct genetic
backgrounds for either a short (3 hr) or long (48 hr) exposure period and their
subsequent mate choice behaviors were scored. We found that the genetic identity
of a previous mate significantly influenced a female's subsequent interest in
males and preference of males. Additionally, a hemiclonal analysis revealed
significant additive genetic variation associated with experience-dependent mate
choice behaviors, indicating a genotype-by-environment interaction for both of
these parameters. We discuss the significance of these results with regard to the
evolution of plasticity in female mate choice behaviors and the maintenance of
variation in harmful male traits.
PMID- 28515890
TI - Sex-dependent infection causes nonadditive effects on kissing bug fecundity.
AB - The influence of parasites on host reproduction has been widely studied in
natural and experimental conditions. Most studies, however, have evaluated the
parasite impact on female hosts only, neglecting the contribution of males for
host reproduction. This omission is unfortunate as sex-dependent infection may
have important implications for host-parasite associations. Here, we evaluate for
the first time the independent and nonindependent effects of gender infection on
host reproductive success using the kissing bug Mepraia spinolai and the
protozoan Trypanosoma cruzi as model system. We set up four crossing treatments
including the following: (1) both genders infected, (2) both genders uninfected,
(3) males infected-females uninfected, and (4) males uninfected-females infected,
using fecundity measures as response variables. Interactive effects of infection
between sexes were prevalent. Uninfected females produced more and heavier eggs
when crossed with uninfected than infected males. Uninfected males, in turn,
sired more eggs and nymphs when crossed with uninfected than infected females.
Unexpectedly, infected males sired more nymphs when crossed with infected than
uninfected females. These results can be explained by the effect of parasitism on
host body size. As infection reduced size in both genders, infection on one sex
only creates body size mismatches and mating constraints that are not present in
pairs with the same infection status. Our results indicate the fitness impact of
parasitism was contingent on the infection status of genders and mediated by body
size. As the fecundity impact of parasitism cannot be estimated independently for
each gender, inferences based only on female host infection run the risk of
providing biased estimates of parasite-mediated impact on host reproduction.
PMID- 28515892
TI - Timing and body condition of dichromatic Black Redstarts during autumn migration.
AB - Individual variation in postjuvenile molt in male Black Redstart is pronounced
with about 90% of young males retaining female-like coloration (cairei plumage
type) and about 10% acquiring adult male-like feathers (paradoxus plumage type).
We examined whether autumn migration timing and body condition differed between
individuals of the two plumage types. We used the data of 10,977 Black Redstarts
captured during autumn at a ringing site in northern Switzerland where a protocol
to record plumage types of captures has been applied since 1980. As cairei
individuals cannot be distinguished from young females while sexing is
comparatively easy for paradoxus individuals, the proportion of missing data on
sex was likely to be higher for cairei individuals than for paradoxus
individuals. We formally accounted for captures with unidentified sex using a
Bayesian approach and conducted a simulation study to show that our approach was
able to provide unbiased results even if the proportion of unsexed captures was
high. Applying the method to the Black Redstart data, we found that the
proportion of individuals with paradoxus plumage type increased from 7.6% in 1980
to 18.1% in 2013. Individuals with the paradoxus plumage type were on average
0.25 g heavier and had 0.62 mm longer third primaries than individuals with the
cairei plumage type. However, we found no support for our expectation of later
migration of paradoxus males compared to cairei individuals based on the
assumption that paradoxus individuals should occupy autumn territories like adult
males. Our results shed new light on the understudied timing of autumn migration
in birds and are in line with available studies on Black Redstarts, suggesting a
molt-constraint that allows only young males in good body condition to molt into
adult-like plumages.
PMID- 28515894
TI - Reproductive ecology of interior least tern and piping plover in relation to
Platte River hydrology and sandbar dynamics.
AB - Investigations of breeding ecology of interior least tern (Sternula antillarum
athalassos) and piping plover (Charadrius melodus) in the Platte River basin in
Nebraska, USA, have embraced the idea that these species are physiologically
adapted to begin nesting concurrent with the cessation of spring floods. Low use
and productivity on contemporary Platte River sandbars have been attributed to
anthropomorphically driven changes in basin hydrology and channel morphology or
to unusually late annual runoff events. We examined distributions of least tern
and piping plover nest initiation dates in relation to the hydrology of the
historical central Platte River (CPR) and contemporary CPR and lower Platte River
(LPR). We also developed an emergent sandbar habitat model to evaluate the
potential for reproductive success given observed hydrology, stage-discharge
relationships, and sandbar height distributions. We found the timing of the late
spring rise to be spatially and temporally consistent, typically occurring in mid
June. However, piping plover nest initiation peaks in May and least tern nest
initiation peaks in early June; both of which occur before the late spring rise.
In neither case does there appear to be an adaptation to begin nesting concurrent
with the cessation of spring floods. As a consequence, there are many years when
no successful reproduction is possible because emergent sandbar habitat is
inundated after most nests have been initiated, and there is little potential for
successful renesting. The frequency of nest inundation, in turn, severely limits
the potential for maintenance of stable species subpopulations on Platte River
sandbars. Why then did these species expand into and persist in a basin where the
hydrology is not ideally suited to their reproductive ecology? We hypothesize the
availability and use of alternative off-channel nesting habitats, like sandpits,
may allow for the maintenance of stable species subpopulations in the Platte
River basin.
PMID- 28515893
TI - Evolutionary stability and the rarity of grandmothering.
AB - The provision of intergenerational care, via the Grandmother Hypothesis, has been
implicated in the evolution of postfertile longevity, particularly in humans.
However, if grandmothering does provide fitness benefits, a key question is why
has it evolved so infrequently? We investigate this question with a combination
of life-history and evolutionary game theory. We derive simple eligibility and
stability thresholds, both of which must be satisfied if intergenerational care
is first to evolve and then to persist in a population. As one threshold becomes
easier to fulfill, the other becomes more difficult, revealing a conflict between
the two. As such, we suggest that, in fact, we should expect the evolution of
grandmothering to be rare.
PMID- 28515891
TI - Longevity is associated with relative brain size in birds.
AB - Brain size of vertebrates has long been recognized to evolve in close association
with basic life-history traits, including lifespan. According to the cognitive
buffer hypothesis, large brains facilitate the construction of behavioral
responses against novel socioecological challenges through general cognitive
processes, which should reduce mortality and increase lifespan. While the
occurrence of brain size-lifespan correlation has been well documented in
mammals, much less evidence exists for a robust link between brain size and
longevity in birds. The aim of this study was to use phylogenetically controlled
comparative approach to test for the relationship between brain size and
longevity among 384 avian species from 23 orders. We used maximum lifespan and
maximum reproductive lifespan as the measures of longevity and accounted for a
set of possible confounding effects, such as allometry, sampling effort,
geographic patterns, and life-history components (clutch size, incubation length,
and mode of development). We found that both measures of longevity positively
correlated with relative (residual) brain size. We also showed that major
diversification of brain size preceded diversification of longevity in avian
evolution. In contrast to previous findings, the effect of brain size on
longevity was consistent across lineages with different development patterns,
although the relatively low strength of this correlation could likely be
attributed to the ubiquity of allomaternal care associated with the altricial
mode of development. Our study indicates that the positive relationship between
brain size and longevity in birds may be more general than previously thought.
PMID- 28515895
TI - Disruptive natural selection predicts divergence between the sexes during
adaptive radiation.
AB - Evolution of sexual dimorphism in ecologically relevant traits, for example, via
resource competition between the sexes, is traditionally envisioned to stall the
progress of adaptive radiation. An alternative view is that evolution of
ecological sexual dimorphism could in fact play an important positive role by
facilitating sex-specific adaptation. How competition-driven disruptive
selection, ecological sexual dimorphism, and speciation interact during real
adaptive radiations is thus a critical and open empirical question. Here, we
examine the relationships between these three processes in a clade of salamanders
that has recently radiated into divergent niches associated with an aquatic life
cycle. We find that morphological divergence between the sexes has occurred in a
combination of head shape traits that are under disruptive natural selection
within breeding ponds, while divergence among species means has occurred
independently of this disruptive selection. Further, we find that adaptation to
aquatic life is associated with increased sexual dimorphism across taxa,
consistent with the hypothesis of clade-wide character displacement between the
sexes. Our results suggest the evolution of ecological sexual dimorphism may play
a key role in niche divergence among nascent species and demonstrate that
ecological sexual dimorphism and ecological speciation can and do evolve
concurrently in the early stages of adaptive radiation.
PMID- 28515896
TI - A worldwide phylogeography of the whiteworm lichens Thamnolia reveals three
lineages with distinct habitats and evolutionary histories.
AB - Thamnolia is a lichenized fungus with an extremely wide distribution, being
encountered in arctic and alpine environments in most continents. In this study,
we used molecular markers to investigate the population structure of the fungal
symbiont and the associated photosynthetic partner of Thamnolia. By analyzing
molecular, morphological, and chemical variation among 253 specimens covering the
species distribution range, we revealed the existence of three mycobiont
lineages. One lineage (Lineage A) is confined to the tundra region of Siberia and
the Aleutian Islands, a second (Lineage B) is found in the high alpine region of
the Alps and the Carpathians Mountains, and a third (Lineage C) has a worldwide
distribution and covers both the aforementioned ecosystems. Molecular dating
analysis indicated that the split of the three lineages is older than the last
glacial maximum, but the distribution ranges and the population genetic analyses
suggest an influence of last glacial period on the present-day population
structure of each lineage. We found a very low diversity of Lineage B, but a
higher and similar one in Lineages A and C. Demographic analyses suggested that
Lineage C has its origin in the Northern Hemisphere, possibly Scandinavia, and
that it has passed through a bottleneck followed by a recent population
expansion. While all three lineages reproduce clonally, recombination tests
suggest rare or past recombination in both Lineages A and C. Moreover, our data
showed that Lineage C has a comparatively low photobiont specificity, being found
associated with four widespread Trebouxia lineages (three of them also shared
with other lichens), while Lineages A and B exclusively harbor T. simplex s. lat.
Finally, we did not find support for the recognition of taxa in Thamnolia based
on either morphological or chemical characters.
PMID- 28515897
TI - Exploitation promotes earlier sex change in a protandrous patellid limpet,
Patella aspera Roding, 1798.
AB - Exploitation of organisms can prompt the reduction in the number and size of
target populations consequently affecting reproductive output and replenishment.
Here, we investigated the effects of exploitation on the population structure of
a protandrous patellid limpet, Patella aspera, an overexploited Macaronesian
endemic. Timed dives were used to collect animals across eleven islands of
Macaronesia. Individuals were inspected for sex, size, and gonad stage. Using
catch effort (time per person) per island coastal perimeter as a surrogate for
exploitation intensity, we found that limpet abundance (CPUE) and mean size
tended to decrease with exploitation intensity. When considering the sex of
animals separately, the size of the largest male, but not females, decreased with
exploitation. In contrast, the size of the smallest male remained relatively
consistent, whereas the size of the smallest female decreased significantly with
exploitation. As exploitation is mostly targeting larger individuals, results
suggest that males are compensating the removal of larger females, by undergoing
sex change at smaller and presumably earlier sizes. These results have wider
implications for the conservation of P. aspera, as a reduction in female size
will likely affect the numbers of oocytes produced, hence fecundity. Regulations
promoting the protection of the larger-sized animals should be enforced to
safeguard the replenishment of the population.
PMID- 28515898
TI - Fungal-host diversity among mycoheterotrophic plants increases proportionally to
their fungal-host overlap.
AB - The vast majority of plants obtain an important proportion of vital resources
from soil through mycorrhizal fungi. Generally, this happens in exchange of
photosynthetically fixed carbon, but occasionally the interaction is
mycoheterotrophic, and plants obtain carbon from mycorrhizal fungi. This process
results in an antagonistic interaction between mycoheterotrophic plants and their
fungal hosts. Importantly, the fungal-host diversity available for plants is
restricted as mycoheterotrophic interactions often involve narrow lineages of
fungal hosts. Unfortunately, little is known whether fungal-host diversity may be
additionally modulated by plant-plant interactions through shared hosts. Yet,
this may have important implications for plant competition and coexistence. Here,
we use DNA sequencing data to investigate the interaction patterns between
mycoheterotrophic plants and arbuscular mycorrhizal fungi. We find no
phylogenetic signal on the number of fungal hosts nor on the fungal hosts shared
among mycoheterotrophic plants. However, we observe a potential trend toward
increased phylogenetic diversity of fungal hosts among mycoheterotrophic plants
with increasing overlap in their fungal hosts. While these patterns remain for
groups of plants regardless of location, we do find higher levels of overlap and
diversity among plants from the same location. These findings suggest that
species coexistence cannot be fully understood without attention to the two sides
of ecological interactions.
PMID- 28515899
TI - Corrigendum.
AB - [This corrects the article DOI: 10.1002/ece3.1910.].
PMID- 28503295
TI - Building the infrastructure to make science metrics more scientific.
AB - Research leaders, policy makers and science strategists need evidence to support
decision-making around research funding investment, policy and strategy. In
recent years there has been a rapid expansion in the data sources available that
shed light onto aspects of research quality, excellence, use, re-use and
attention, and engagement. This is at a time when the modes and routes to share
and communicate research findings and data are also changing. In this opinion
piece, we outline a series of considerations and interventions that are needed to
ensure that research metric development is accompanied by appropriate scrutiny
and governance, to properly support the needs of research assessors and decision
makers, while securing the confidence of the research community. Key among these
are: agreed 'gold standards' around datasets and methodologies; full transparency
around the calculation and derivation of research-related indicators; and a
strategy and roadmap to take the discipline of scientific indicators and research
assessment to a more robust and sustainable place.
PMID- 28515902
TI - Sites of colonization in hospitalized patients with infections caused by extended
spectrum beta-lactamase organisms: a prospective cohort study.
AB - BACKGROUND: The objective of this study was to determine whether patients
infected with extended-spectrum beta-lactamase (ESBL)-producing organisms are
colonized at multiple body sites. METHODS: This was a prospective cohort study at
a tertiary care center in Beirut, Lebanon. Hospitalized patients with infections
caused by ESBL-producing organisms were included. Cultures were obtained from the
primary site of infection as well as from other sites (skin, nasopharynx, urine,
rectum). Molecular analysis was performed on isolates to determine clonal
relatedness. RESULTS: One hundred patients were included in the study. Only 22
patients had positive cultures from sites other than the primary site of
infection. The most common ESBL gene was CTX-M-15 followed by TEM-1. In 11 of 22
patients, isolates collected from the same patient were 100% genetically related,
while in the remaining patients, genomic relatedness ranged from 42.9% to 97.1%.
CONCLUSIONS: Colonization at sites other than the primary site of infection was
not common among our patient population infected with ESBL-producing organisms.
The dynamics of transmission of these bacterial strains should be studied in
further prospective studies to determine the value of routine active surveillance
and the need for expanded precautions in infected and colonized patients.
PMID- 28515901
TI - Experimental identification and computational characterization of a novel
extracellular metalloproteinase produced by Clostridium sordellii.
AB - Clostridium sordellii is a lethal pathogen for both animals and humans. Severe
capillary leakage, toxic shock syndrome, and an extreme leukemoid reaction (LR),
are hallmark features of C. sordellii infections and contribute to its high
mortality rate. Here we report the discovery of a previously unknown and
uncharacterized metalloproteinase of C. sordellii (referred as Mcs1) that cleaves
human vascular cell adhesion molecule (VCAM)-1 in vitro, an adhesion molecule
critical to hematopoietic precursor retention and leukocyte diapedesis. We
successfully identified the open reading frame encoding Mcs1 within the ATCC 9714
genome and developed an Deltamcs1 mutant strain using the ClosTron mutagenesis
technology. No VCAM-1 proteolysis was observed from exotoxins collected from
mutant strain cultures. Using advanced protein structural modeling and molecular
dynamics simulation techniques, the 3D molecular structure and conformational
features of Mcs1 were also characterized. Our data demonstrates that Mcs1
proteolytic activity is controlled by the electrostatic interactions between
Glu113 and Arg227 residues and the gating motions within its cleft region. This
pilot interdisciplinary investigation provided crucial experimental evidence of
the existence of Mcs1 in C. sordellii and molecular insights into its 3D
structure and proteolytic activity. These findings have the potential to help
advance new therapeutics and diagnostics against deadly C. sordellii infections.
Follow-up in vitro and in vivo work is under way to further characterize Mcs1
enzymatic kinetics and its role in C. sordellii pathogenesis.
PMID- 28515904
TI - Weekly screening supports terminating nosocomial transmissions of vancomycin
resistant enterococci on an oncologic ward - a retrospective analysis.
AB - BACKGROUND: To investigate the impact of weekly screening within the bundle of
infection control measures to terminate vancomycin-resistant enterococci (VRE)
transmissions on an oncologic ward. METHODS: A cluster of 12 VRE colonisation and
five infections was detected on an oncologic ward between January and April 2015.
Subsequently, the VRE point prevalence was detected and, as part of a the bundle
of infection control strategies to terminate the VRE cluster, we isolated
affected patients, performed hand hygiene training among staff on ward, increased
observations by infection control specialists, intensified surface disinfection,
used personal protective equipment and initiated an admission screening in May
2015. After a further nosocomial VRE infection in August 2015, a weekly screening
strategy of all oncology patients on the respective ward was established while
admission screening was continued. Whole genome sequencing (WGS)-based typing was
applied to determine the clonal relationship of isolated strains. RESULTS:
Initially, 12 of 29 patients were VRE colonised; of these 10 were hospital
acquired. During May to August, on average 7 of 40 patients were detected to be
VRE colonised per week during the admission screening, showing no significant
decline compared to the initial situation. WGS-based typing revealed five
different clusters of which three were due to vanB- and two vanA-positive
enterococci. After an additional weekly screening was established, the number of
colonised patients significantly declined to 1/53 and no further nosocomial cases
were detected. CONCLUSIONS: Weekly screening helped to differentiate between
nosocomial and community-acquired VRE cases resulting in earlier infection
control strategies on epidemic situations for a successful termination of
nosocomial VRE transmissions.
PMID- 28515903
TI - The threat of antimicrobial resistance in developing countries: causes and
control strategies.
AB - The causes of antimicrobial resistance (AMR) in developing countries are complex
and may be rooted in practices of health care professionals and patients'
behavior towards the use of antimicrobials as well as supply chains of
antimicrobials in the population. Some of these factors may include inappropriate
prescription practices, inadequate patient education, limited diagnostic
facilities, unauthorized sale of antimicrobials, lack of appropriate functioning
drug regulatory mechanisms, and non-human use of antimicrobials such as in animal
production. Considering that these factors in developing countries may vary from
those in developed countries, intervention efforts in developing countries need
to address the context and focus on the root causes specific to this part of the
world. Here, we describe these health-seeking behaviors that lead to the threat
of AMR and healthcare practices that drive the development of AMR in developing
countries and we discuss alternatives for disease prevention as well as other
treatment options worth exploring.
PMID- 28515906
TI - Measurement accuracy of total cell volume by automated dialyzer reprocessing: A
prospective cohort study.
AB - INTRODUCTION: Dialyzer reprocessing machines have replaced human labor in
preparing re-usable dialyzers. It also made the process of total cell volume
(TCV) measurement become faster. Nevertheless, there has been a lack of data on
efficacy of weight evaluation on TCV by machine compared to volume evaluation by
the conventional method. The aim of this study was to evaluate the efficacy of
TCV measurement performed by Kidney-Kleen(r) reprocessing machine, produced by
MEDITOP Company in Thailand, compared to that of the conventional method.
METHODS: This prospective cohort study was performed during September 2014 to
December 2015.The low-flux (N = 101) and high-flux dialyzers (N = 100) were
included for TCV evaluation. Reused times were up to 5 in the low-flux and 20 in
the high-flux dialyzers. The Bland Altman analysis was used to evaluate value
measured by different methods. RESULTS: The values measured by weight evaluation
(by machine) were higher than those obtained by volumetric evaluation of the
conventional method in the low-flux (0.81 +/- 0.20%) and high-flux (1.32 +/-
0.39%) dialyzers. The correlation of TCV values of the two methods were r = 0.98,
p < 0.001 and r = 0.71, p < 0.001 for the low- and high-flux dialyzers. Moreover,
there was robust association and agreement between the two methods, confirmed by
the Bland-Altman Analysis, which suggested that the values acquired by machine
were within the limits of agreement, indicating acceptable accuracy of equipment.
CONCLUSION: The approach of measurement differed from that of the conventional
method (weight evaluation was used instead of volumetric evaluation), the
reprocessing machine could offer accurate results.
PMID- 28515905
TI - Colonization of long term care facility patients with MDR-Gram-negatives during
an Acinetobacter baumannii outbreak.
AB - BACKGROUND: We aimed to determine the prevalence of colonization by multidrug
resistant Gram-negative bacteria including ESBL-producing enterobacteriaceae,
carbapenem-resistant enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter
baumannii at two wards caring long term for patients with disorder of
consciousness at the Geriatric Health Centers Graz, Austria. During our study we
detected two A. baumannii outbreaks. METHODS: In August 2015, we conducted a
point-prevalence study. Inguinal and perianal swabs were taken from 38 patients
and screened for multidrug-resistant Gram-negative rods using standard
procedures. Six months after the initial investigation all patients were sampled
again and use of antibiotics during the past 6 months and mortality was
registered. Genetic relatedness of bacteria was evaluated by DiversiLab system.
RESULTS: Fifty percent of patients were colonized by multidrug-resistant Gram
negative isolates. Five patients harboured ESBL-producing enterobacteriaceae. No
carbapenem-resistant enterobacteriaceae were detected. 13/38 patients were
colonized by A. baumannii isolates (resistant to ciprofloxacin but susceptible to
carbapenems). There was a significant difference in the prevalence of
colonization by A. baumannii between ward 2 and ward 1 (60% vs. 5.6%, p < 0.001).
Two clusters of A. baumannii isolates were identified including one isolate
detected on a chair in a patient's room. CONCLUSIONS: We detected a high
prevalence of two multidrug-resistant A. baumannii strains in patients with
disorder of consciousness at a LTCF in Graz, Austria. Our findings strongly
suggest nosocomial cross-transmission between patients. An active surveillance
strategy is warranted to avoid missing newly emerging pathogens.
PMID- 28515663
TI - Measurement of jet activity produced in top-quark events with an electron, a muon
and two b-tagged jets in the final state in pp collisions at [Formula: see text]
TeV with the ATLAS detector.
AB - Measurements of jet activity in top-quark pair events produced in proton-proton
collisions are presented, using 3.2 fb[Formula: see text] of pp collision data at
a centre-of-mass energy of 13 TeV collected by the ATLAS experiment at the Large
Hadron Collider. Events are chosen by requiring an opposite-charge [Formula: see
text] pair and two b-tagged jets in the final state. The normalised differential
cross-sections of top-quark pair production are presented as functions of
additional-jet multiplicity and transverse momentum, [Formula: see text]. The
fraction of signal events that do not contain additional jet activity in a given
rapidity region, the gap fraction, is measured as a function of the [Formula: see
text] threshold for additional jets, and is also presented for different
invariant mass regions of the [Formula: see text] system. All measurements are
corrected for detector effects and presented as particle-level distributions
compared to predictions with different theoretical approaches for QCD radiation.
While the kinematics of the jets from top-quark decays are described well, the
generators show differing levels of agreement with the measurements of
observables that depend on the production of additional jets.
PMID- 28515907
TI - Factors influencing risky single occasion drinking in Canada and policy
implications.
AB - BACKGROUND: Misuse of alcohol, including single risky occasion drinking (RSOD) is
associated with a number of health, social and economic consequences. While
research demonstrates that many factors contribute to individuals' drinking
practices, little is known about risk factors that contribute to RSOD in the
Canadian population. The objectives of this study are to examine the patterns of
RSOD in Canada, to identify factors associated with RSOD, and to explore policy
implications. METHODS: The Canadian Community Health Survey (CCHS) 2009-2010
annual component was used to conduct all the analyses in this paper. We used two
models: (1) a binary logistic regression model, and (2) a multinomial logistic
regression model, to identify factors that were significantly associated with our
dependent variables, RSOD engagement and frequency of RSOD, respectively.
RESULTS: Daily smokers were 6.20 times more likely to engage in frequent RSOD
than those who never smoke. Males were 4.69 times more likely to engage in risky
RSOD. We also found significant associations between the frequency of RSOD and
Province/Territory of residence, income and education, marital status and
perceived health status. Finally, stress was associated with engaging in
infrequent RSOD. CONCLUSIONS: Our finding associating daily smoking with risk
alcohol intake specifically suggests the possibility of combining public health
interventions for both. The study findings also indicate that education is a
protective factor, further supporting the role of education as a major
determinant of health. The significant provincial variation we found also point
to the need to study this issue further and understand the links between
provincial level policies and RSOD.
PMID- 28515908
TI - Renal manifestations of primary mitochondrial disorders.
AB - The aim of the present review was to summarize and discuss previous findings
concerning renal manifestations of primary mitochondrial disorders (MIDs). A
literature review was performed using frequently used databases. The study
identified that primary MIDs frequently present as mitochondrial multiorgan
disorder syndrome (MIMODS) at onset or in the later course of the MID.
Occasionally, the kidneys are affected in MIDs. Renal manifestations of MIDs
include renal insufficiency, nephrolithiasis, nephrotic syndrome, renal cysts,
renal tubular acidosis, Bartter-like syndrome, Fanconi syndrome, focal segmental
glomerulosclerosis, tubulointerstitial nephritis, nephrocalcinosis, and benign or
malign neoplasms. Among the syndromic MIDs, renal involvement has been most
frequently reported in patients with mitochondrial encephalomyopathy, lactic
acidosis, and stroke-like episodes syndrome, Kearns-Sayre syndrome, Leigh
syndrome and mitochondrial depletion syndromes. Only in single cases was renal
involvement also reported in chronic progressive external ophthalmoplegia,
Pearson syndrome, Leber's hereditary optic neuropathy, coenzyme-Q deficiency, X
linked sideroblastic anemia and ataxia, myopathy, lactic acidosis, and
sideroblastic anemia, pyruvate dehydrogenase deficiency, growth retardation,
aminoaciduria, cholestasis, iron overload, lactacidosis, and early death, and
hyperuricemia, pulmonary hypertension, renal failure in infancy and alkalosis
syndrome. The present study proposes that the frequency of renal involvement in
MIDs is probably underestimated. Diagnosis of renal involvement follows general
guidelines and treatment is symptomatic. Thus, renal manifestations of primary
MIDs require recognition and appropriate management, as they determine the
outcome of MID patients.
PMID- 28515909
TI - Metabolic role of fibroblast growth factor 21 in liver, adipose and nervous
system tissues.
AB - The hepatokine fibroblast growth factor 21 (FGF21) is a novel polypeptide ligand,
which is involved in glucose and lipid metabolism, and contributes significantly
to lowering body weight and enhancing insulin sensitivity. A large number of pre
clinical and clinical results demonstrate that FGF21 is a potential drug target
for treating obesity and type 2 diabetes mellitus. In the present review, the
tissue specific actions and molecular mechanisms of FGF21 are discussed with a
focus on the liver, adipose tissue and nervous system, as well as investigating
the outcomes of clinical trials of FGF21, with the aim of interpreting and
delineating the complexity physiology of FGF21.
PMID- 28515910
TI - Biocompatibility of biological material polylactic acid with stem cells from
human exfoliated deciduous teeth.
AB - To investigate the biocompatibility of the biomaterial, polylactic acid (PLA)
with stem cells from human exfoliated deciduous teeth (SHED) and its induction of
mineralization as a type of scaffold material. To determine the impacts of
biomaterial PLA on proliferation and mineralization of SHED, the expression of
surface molecules of SHED isolated and cultured in vitro was detected by flow
cytometry. In addition, cell proliferation was measured using MTT and Edu assays,
and the evaluation of mineralized differentiation was performed using Alizarin
Red S staining. In addition, the expression levels of osteogenic marker genes
were measured by reverse transcription-quantitative polymerase chain reaction (RT
qPCR) and western blot analysis. SHED were successfully isolated and identified.
The MTT and Edu results indicated that the proliferation of SHED cultured in PLA
and normal medium was not significantly different. The Alizarin Red S staining
demonstrated that the mineralization capability was significantly higher in the
SHED that were cultured in PLA medium. Furthermore, RT-qPCR and western blot
analyses indicated that the expression levels of osteogenic marker genes were
higher in the SHED cultured in PLA medium. These results suggested that PLA
possesses good biocompatibility with SHED and may effectively induce the
mineralization of SHED and serve as a scaffold material.
PMID- 28515912
TI - Accelerated carcinogenesis following liver resection in chronically inflamed
livers: A window of opportunity for treatment.
AB - The long-term prognosis following resection of hepatocellular carcinoma (HCC)
remains unsatisfactory as a result of a high incidence of recurrence. Prevention
of recurrence is the most important strategy to improve the long-term survival
results. The role of hepatectomy itself, as an accelerator of carcinogenesis, has
not been adequately evaluated in HCC patients. Studies in animal models have
revealed a link between liver regeneration under chronic inflammation and hepatic
tumorigenesis. Inhibiting different signal transduction pathways during liver
regeneration without compromising the ability of the liver to regenerate appears
to be a rational strategy and may decrease HCC development and recurrence. If
this hypothesis is proven using animal models, this strategy could be evaluated
in future clinical trials in humans.
PMID- 28515916
TI - ECOG is as independent predictor of the response to chemotherapy, overall
survival and progression-free survival in carcinoma of unknown primary site.
AB - The aim of the present study was to determine whether age, gender, functional
status, histology, tumor location, number of metastases, and levels of the tumor
markers, lactate dehydrogenase (LDH) and albumin, are poor prognostic factors for
the response to chemotherapy in patients with carcinoma of unknown primary site.
A total of 149 patients diagnosed with carcinoma of unknown primary site that was
histologically confirmed, and treated with chemotherapy in the Oncology Hospital,
National Medical Center, 'Century XXI' IMSS, Mexico City, Mexico during the
period between January 2002 to December 2009, were carefully selected for the
present study. The analysis of 149 patients diagnosed with carcinoma of unknown
primary site revealed that the liver was the organ with the highest frequency of
metastases (33.5%). The objective response rates to chemotherapy were ~30.2%.
Notably, ECOG was an important predictor of response to chemotherapy (P=0.008).
The median progression-free survival was 7.1 months. Upon multivariate analysis,
the Eastern Cooperative Oncology Group (ECOG) Scale of Performance Status was
observed as an independent predictor of progression (P<0.0001). The median
overall survival was 14.2 months. The ECOG was also an independent predictor of
mortality (P<0.0001). In conclusion, the data from the present study have
demonstrated that ECOG is an independent predictor of a poor response to
chemotherapy, lower overall survival and progression-free survival in carcinoma
of unknown primary site.
PMID- 28515922
TI - Primary primitive neuroectodermal tumor of the cervix: A report of two cases and
review of the literature.
AB - Peripheral primitive neuroectodermal tumor (PNET) of the cervix uteri is
extremely rare. Two cases of PNET of the cervix are presented herein. Two female
patients, aged 48 and 43 years, presented with irregular uterine bleeding over
the course of 1 year, and increased urinary frequency for 1 month, respectively.
On gynecological examination, a mass in the cervix was palpated and a biopsy
performed. The findings of the initial biopsy revealed small-cell carcinoma in
both patients. Following neoadjuvant chemotherapy and radiotherapy, radical
hysterectomy was performed in both patients. One patient received 5 courses of
consolidation chemotherapy and postoperative radiotherapy, whereas the other
patient received 1 course of consolidation chemotherapy. At the time of the
article submission, both patients remained disease-free at 27 and 12 months,
respectively, after their initial diagnosis. Only a limited number of cases of
PNET of the cervix uteri have been reported in the literature to date. Multimodal
therapies, including total excision, adjuvant chemotherapy and/or radiotherapy,
have been adopted to treat patients with PNET of the cervix.
PMID- 28515918
TI - Synchronous primary malignant neoplasms of the cervix and endometrium.
AB - Synchronous multiple malignant neoplasms of the female genital tract are rare,
particularly in the uterus. We herein present the case of a patient with
synchronous cervical squamous epithelial carcinoma and endometrial
adenocarcinoma, and discuss the diagnosis, treatment and prognosis. The patient
underwent a cervical biopsy and fractional curettage of the endometrium, followed
by abdominal staging surgery, including radical hysterectomy, bilateral salpingo
oophorectomy, pelvic and para-aortic lymphadenectomy. The diagnosis was stage Ib1
cervical cancer and stage Ia endometrial cancer, without lymph node metastases.
There has been no recurrence during 1 year of followup. Synchronous genital tract
neoplasms are more clinically complex compared with single neoplasms and it is
crucial to focus on the differential diagnosis between primary and metastatic
tumors during the diagnostic process. The treatment of synchronous genital tract
neoplasms also differs significantly from that of single neoplasms, although the
prognosis of patients with synchronous gynecological malignancies does not appear
to be worse.
PMID- 28515921
TI - Association between periodontitis and prognosis of pancreatobiliary tract cancer:
A pilot study.
AB - Several studies have indicated that periodontitis is a risk factor for cancer.
However, the association between periodontitis and the prognosis of
pancreatobiliary tract cancer remains unclear. The aim of this pilot study was to
investigate the association between periodontitis and prognosis of
pancreatobiliary tract cancer. A total of 22 patients diagnosed with
pancreatobiliary tract cancer were analyzed. Oral health status, including
severity of periodontitis, general health status and biochemical serum markers
were evaluated. The Kaplan-Meier method and Cox proportional hazards model were
used to assess factors affecting the prognosis of pancreatobiliary tract cancer.
The Kaplan-Meier analysis demonstrated that low body mass index, high
concentration of serum C-reactive protein (CRP) and severe periodontitis were
significant prognostic factors for survival rate. The Cox proportional hazards
model revealed that serum carbohydrate antigen 19-9 concentration [hazard ratio
(HR)=1.002; 95% confidence interval (CI): 1.000-1.004] and serum CRP
concentration (HR=2.57; 95% CI: 1.15-5.74) were significantly associated with the
prognosis of pancreatobiliary tract cancer. In addition, cancer patients with
severe periodontitis had higher serum CRP concentrations compared with those
without severe periodontitis. Therefore, severe periodontitis indirectly affected
the prognosis of pancreatobiliary tract cancer through promoting systemic
inflammation.
PMID- 28515917
TI - Total laparoscopic hysterectomy for large uterine cervical myoma.
AB - Ureterolysis is a surgical method with a high level of difficulty, which may be
necessary when performing total laparoscopic hysterectomy (TLH) for large
cervical myoma, despite the benign nature of this tumor. The aim of the present
study was to introduce techniques that are commonly applied in malignant tumor
surgery in order to safely perform TLH for large cervical myoma. Between 2014 and
2016, TLH was performed at the Shimane University Hospital (Izumo, Japan) in 153
patients with benign tumors, including 25 cases with a large uterus (uterine
weight >=500 g). The surgical methods applied in 3 of these large uterine
cervical myoma cases were investigated in detail, including techniques devised by
our department. TLH was performed without enucleating myomectomy in all 3 cases;
however, all 3 cases required ureterolysis, transection of the anterior layer of
the vesicouterine ligament and isolation of the ureter. In conclusion, although
radical laparoscopic hysterectomy is commonly performed for cervical cancer at
our department, techniques used for malignant tumor surgery may prove useful for
benign cases with a high level of difficulty.
PMID- 28515913
TI - Promoter polymorphisms of the vascular endothelial growth factor gene are
associated with metabolic syndrome susceptibility in Koreans.
AB - Vascular endothelial growth factor (VEGF) is a potent regulator of angiogenesis.
Patients with metabolic syndrome (MetS) have elevated plasma VEGF levels. The aim
of the present study was to investigate the association between promoter
polymorphisms (the -2578C>A and -1154G>A) of the VEGF gene and MetS
susceptibility. A total of 640 subjects were enrolled in the study including 320
patients with MetS and 320 healthy controls. Genotyping of the VEGF single
nucleotide polymorphisms was performed by polymerase chain reaction-restriction
fragment length polymorphism analysis. The CA and AA genotypes of the -2578C>A
polymorphism were associated with decreased risk of MetS (P=0.018, P=0.003,
respectively). For the -1154G>A polymorphism, although the GA genotype was more
significantly frequent in MetS patients (P=0.022), the AA genotype and recessive
model (GG+GA vs. AA) were protective against MetS susceptibility (P=0.016, 0.007,
respectively). The A-G haplotype frequency composed of the -2578C>A and -1154G>A
polymorphisms also differed between the 2 groups (P=0.011). The presented data
suggested that the A alleles and A-G haplotype of the VEGF -2578C>A and -1154G>A
polymorphisms are associated with decreased MetS susceptibility. To the best of
the authors' knowledge, the current study is the first to investigate the
associations between the VEGF -2578C>A and -1154G>A polymorphisms and MetS
patients. Further evaluation is necessary to explore the associations between the
VEGF polymorphisms and MetS patients in larger samples of other ethnic or racial
populations.
PMID- 28515911
TI - Expression of tubulin folding cofactor B in mouse hepatic ischemia-reperfusion
injury.
AB - The aim of the present study was to investigate the association between tubulin
folding cofactor B (TBCB) expression and ischemia-reperfusion injury (IRI) in
mice. A total of 48 C57BL/6 mice were randomly divided into a control group
(Sham, n=6) and an ischemia-reperfusion group (n=42). The ischemia-reperfusion
group was further divided into 6 subgroups as per different times after
reperfusion (2, 4, 6, 8, 12 and 24 h), with 7 mice per subgroup. A hepatic IRI
model was established in mice by clamping the hepatic hilum. Morphology, serum
levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST),
interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), and the
expression level of TBCB were detected. Compared with the control group, the
livers from the ischemia-reperfusion group were significantly changed,
particularly at 12 h following ischemia-reperfusion, with obvious hepatic cell
degeneration and necrosis. The ALT, AST, IL-6 and TNF-alpha levels in the sera of
the mice in the hepatic ischemia-reperfusion group were increased at all time
points following ischemia-reperfusion, and were the highest at 12 h,
demonstrating statistically significant differences when compared with the
control group (P<0.05). Furthermore, the expression levels of TBCB, TNF-alpha and
IL-6 were significantly increased at all time-points following ischemia
reperfusion, and were the most significant at 12 h. At 24 h following ischemia
reperfusion, the expression levels had decreased. The present study indicated
that TBCB expression is associated with TNF-alpha and IL-6 expression levels in
mice with hepatic ischemia-reperfusion, and may be key in the development of
liver injury during ischemia-reperfusion in mice.
PMID- 28515914
TI - Analysis of the function of microRNA-375 in humans using bioinformatics.
AB - MicroRNA-375 (miR-375) is expressed at low levels in many types of solid tumor,
particularly in gastrointestinal tumors. It is considered to be important in the
development of cancer and certain diseases. Thus, more detailed knowledge is
required on the particular functions of miR-375. miRs function by regulating
target genes. Therefore, in the current study, miRWalk (which includes the data
from 10 prediction software programs) was used to predict the target genes of miR
375. The genes, which were co-predicted using five different software programs
were further analyzed using Database for Annotation, Visualization and Integrated
Discovery online software [including gene ontology (GO) and Kyoto Encyclopedia of
Genes and Genomes (KEGG) pathway analysis]. Subsequently, the online tool, Search
Tool for the Retrieval of Interacting Genes, was used to analyze the protein
protein interaction and construct modules using Cytoscape. The result
demonstrated 6,574 predicted genes, 1,325 of which were co-predicted. The GO
analysis result indicated that, in biological processes, the co-predicted genes
were significantly enriched in the regulation of nervous system development and
cell differentiation, and the highest enrichment of molecular function was ion
binding. In KEGG analysis, the genes were enriched in the Hippo signaling
pathway, glutamatergic synapse, circadian entrainment and the phosphoinositide 3
kinase (PI3K)-Akt signaling pathway. The top 10 hub proteins were mechanistic
target of rapamycin, PH domain and leucine rich repeat protein phosphatase 1,
ubiquitously transcribed tetratricopeptide repeat containing, Y-linked, histone
deacetylase 2, F-box and leucine rich repeat protein 19, KIT proto-oncogene
receptor tyrosine kinase, angiotensinogen, Janus kinase 2, fibroblast growth
factor 2 and RNA polymerase II subunit A. These proteins predominantly regulate
the development and progression of cancer, hypertension, essential
thrombocythemia and inflammation. The genes in the top seven modules selected
were identified to be primarily enriched in chemokines, extracellular matrix
receptor interaction, focal adhesion, the PI3K-Akt signaling pathway, amoebiasis
and protein processing signaling pathway. Thus, the target genes and hub proteins
that were predicted in the current study were identified to be important in
regulating the development and progression of cancer and certain diseases.
Furthermore, they present potential novel biomarkers for tumor diagnosis and
candidate targets for treatment, and indicate that further research is required
to establish the functions of miR-375.
PMID- 28515915
TI - Superior effects of quetiapine compared with aripiprazole and iloperidone on MK
801-induced olfactory memory impairment in female mice.
AB - Cognitive dysfunction is commonly observed in schizophrenic patients and the
administration of antipsychotic treatments results in different outcomes.
Although the typical antipsychotic treatments, such as haloperidol, appear to be
unable to improve cognition dysfunction, the atypical antipsychotic drugs
(quetiapine, aripiprazole and iloperidone) exert a beneficial effect. The purpose
of the current study was to investigate the effects of atypical antipsychotics on
olfactory memory in mice, utilizing the social transmission of food preference
(STFP) tests to evaluate the effects of drugs on MK-801-induced cognitive
dysfunction. Female BALB/c mice were treated with quetiapine (5 and 10 mg/kg),
aripiprazole (3 and 6 mg/kg), iloperidone (0.5 and 1 mg/kg) or MK-801 (0.1 mg/kg)
alone or concurrently prior to retention sessions of STFP tests. In the STFP
tests, quetiapine (10 mg/kg; P<0.05), aripiprazole (3 and 6 mg/kg; P<0.01 and
P<0.001, respectively), iloperidone (0.5 and 1 mg/kg; P<0.01 and P<0.001,
respectively) and MK-801 (P<0.001) significantly decreased cued/total food eaten
(%). Quetiapine (5 mg/kg; P<0.05) significantly increased MK-801-induced
decreases in cued/total food eaten (%), while aripiprazole and iloperidone
demonstrated no significant effects. The results revealed that all of the drugs
disturbed olfactory memory in the naive mice; however, only quetiapine reversed
MK-801-induced memory impairment in the STFP test.
PMID- 28515920
TI - Predictive value of the modified Glasgow Prognostic Score for the therapeutic
effects of molecular-targeted drugs on advanced renal cell carcinoma.
AB - Inflammation is considered to be a prognostic factor for renal cell carcinoma
(RCC). An inflammation-based prognostic score (modified Glasgow Prognostic Score;
mGPS) is widely used for preoperative patients; however, little information is
available regarding its prognostic value in patients with RCC treated with
molecular-targeted drugs. A total of 32 advanced and recurrent RCC patients
initially treated with molecular-targeted drugs from October, 2009 to August,
2015 were retrospectively investigated. Information on patient characteristics
prior to treatment initiation and the clinical course were retrieved from
clinical records. The correlation between survival and patient variables was
analyzed. Survival was compared among patient groups according to the mGPS score.
The median patient age was 66 years. The percentage of patients with an Eastern
Cooperative Oncology Group performance status of 0 or 1 was 87.5, and 65.6% of
the RCCs were clear cell carcinomas. A Memorial Sloan-Kettering Cancer Center
index of good or intermediate was determined for 75% of the patients. Sunitinib,
pazopanib or sorafenib was administered to 56, 22 and 13% of the cases,
respectively. An mGPS score of 0, 1 and 2 was calculated for 66, 9 and 25% of the
cases, respectively. Patients in the mGPS low group (score 0) exhibited
significantly better progression-free survival (PFS) and overall survival (OS)
compared with patients in the mGPS high group (score 1 or 2) (median PFS, 307 vs.
70 days and median OS, 1,081 vs. 140 days, respectively). In conclusion,
inflammatory status as assessed by the mGPS score was closely associated with the
prognosis of RCC patients treated with molecular-targeted therapy.
PMID- 28515923
TI - Expression of CXCR-4 and IDO in human colorectal cancer: An immunohistochemical
approach.
AB - C-X-C chemokine receptor type 4 (CXCR4), the receptor for the chemokine stromal
cell-derived factor (SDF)-1 [also known as C-X-C motif chemokine 12 (CXCL12)], is
involved in lymphocyte trafficking. Recent studies have demonstrated that, during
pregnancy, a placental enzyme called indoleamine 2, 3-dioxygenase (IDO) exerts a
key role in suppressing the maternal T-cell response against the fetus. In the
present study, the significance of CXCR4 and IDO expression in human colorectal
cancer (CRC) has been investigated by immunohistochemical assay, and their
association with survival was analyzed. Tumor specimens (n=60) from patients with
different American Joint Committee on Cancer (AJCC) stages of CRC (I or IV) were
assessed. In the stage IV group, 23 of 30 cases (77%) stained positive for CXCR4,
and 9 of 30 (30%) were positive for IDO. By contrast, in the stage I group, 7 of
30 cases (23%) stained positive for CXCR4, and 15 of 30 cases (50%) were positive
for IDO. The 5-year survival rate of those with high CXCR4 expression in tumor
specimens (n=30) was significantly worse compared with those with negative CXCR4
expression (16.3 vs. 60.7%, P=0.02). By contrast, the 5-year survival rate of
those with high IDO expression in tumor specimens (n=24) was not significantly
different compared with those with negative IDO expression (36.4 vs. 56.8%). In
the stage I group, 4 patients in the high IDO expression group (n=15) had distant
metastases (2 in the liver 1 in the brain, and 1 in the lung). Taken together,
CXCR4 appears to be a novel predictive indicator of survival, and IDO expression
in the early stage may be a predictor of distant metastasis.
PMID- 28515919
TI - Programmed death-ligand 1 expression is associated with fibrosarcomatous
transformation of dermatofibrosarcoma protuberans.
AB - Dermatofibrosarcoma protuberans (DFSP) is a locally invading tumor, characterized
by the presence of the collagen type I alpha 1 (COL1A1)-platelet-derived growth
factor (PDGF) beta fusion gene. We herein report the case of a 31-year-old man
with a history of resection of an abdominal wall DFSP. The patient presented with
chest pain and a computed tomography scan revealed a large mass in the posterior
mediastinum and another mass in the right lung. The mediastinal mass was a
sarcomatous lesion expressing the COL1A1-PDGFbeta fusion gene, suggesting that it
represented a metastasis of the DFSP following fibrosarcomatous (FS)
transformation. Following resection of the mediastinal metastasis and subsequent
radiotherapy, the mass in the right lung was also resected. Due to the emergence
of pleural and pancreatic tail metastases, the patient was treated with a
combination therapy of adriamycin and ifosfamide. After five courses, the disease
progressed and the patient was subsequently treated with pazopanib for ~2 months
until further progression. Three years after the diagnosis of the mediastinal
metastasis of DFSP, the patient was referred to another hospital for palliative
care. The expression of programmed cell death 1 ligand (PD-L1) in the primary and
metastatic tumors was investigated: PD-L1 expression was detected in the
metastasis but not in the primary tumor. Given that the metastatic tumor
exhibited FS transformation (DFSP-FS), PD-L1 expression may be induced by FS
transformation, contributing to the metastasis through escape from immune
surveillance. Further investigation of the PD-L1 pathway in DFSP and DFSP-FS in
primary as well as metastatic sites is required to evaluate the clinical efficacy
of therapies targeting the PD-L1 signaling cascade.
PMID- 28515925
TI - Nipple-sparing mastectomies: Clinical outcomes from a single academic
institution.
AB - Nipple-sparing mastectomies (NSMs) are increasingly used in the surgical
treatment of patients with breast cancer and for prevention of breast cancer. The
present study was performed to review the outcomes of patients undergoing NSMs at
a single large university setting. A retrospective chart review was performed on
all patients undergoing NSMs from 2008-2014. Charts were reviewed for demographic
data and patient characteristics. Tumor and breast size, cancer recurrence and
complications were also evaluated. Descriptive statistics were utilized to
summarize the findings. From 2008-2014, 110 patients underwent 197 NSMs. The mean
patient age was 44.4 years (range, 20-77). The average body mass index was 24
(range, 18-47). Breast weight was available for 106 specimens, with a mean weight
of 475.5 g (range, 124.1-1,625.0 g). Seventy-three NSMs were performed for cancer
and 124 were performed prophylactically. The mean tumor width was 1.38 cm (range,
0-6.0 cm), with an average nipple to tumor distance of 5.87 cm (range, 2.93-10.0
cm). Three (4%) patients required removal of the nipple areolar complex (NAC) due
to pathological extension of the tumor. A total of 34 (17.2%) complications
occurred, including infections, hematomas and nipple necrosis, with 9 requiring
removal of the NAC and 13 requiring removal of the tissue expander or implant.
Smokers had a 36.0% (9/25) complication rate, compared with 14.5% (25/172) of
nonsmokers (P<0.05). During follow-up, one recurrence was noted, located on the
chest wall. There were no recurrences in the NAC group. Therefore, NSMs may
safely be performed without compromising oncologic outcomes or increasing
complication rates in properly selected patients.
PMID- 28515926
TI - Cisplatin-based chemoradiotherapy with 5-fluorouracil or pemetrexed in patients
with locally advanced, unresectable esophageal squamous cell carcinoma: A
retrospective analysis.
AB - Treatment with 5-fluorouracil (5-FU) and cisplatin (PF regimen) remains the most
frequently used chemotherapy for esophageal squamous cell carcinoma (SCC). The
aim of the present study was to assess the efficacy and safety of
pemetrexed/cisplatin (PP regimen) as definitive treatment compared with PF. A
total of 60 patients with locally advanced, unresectable SCC of the esophagus
receiving concomitant chemoradiotherapy were recruited in this study; of those
patients, 29 received four cycles (two concomitant and two post-radiotherapy) of
the PF regimen (arm A, cisplatin 25 mg/m2/day i.v. on days 1-3 plus 5-FU 800
mg/m2/24 h by continuous infusion on days 1-5) and 31 received four cycles of the
PP regimen (arm B, cisplatin 25 mg/m2/day i.v. on days 1-3 plus pemetrexed 500
mg/m2 on day 1). All the patients in both arms received a total radiation dose of
59.6 Gy. The two arms were well-matched for age, gender, Karnofsky performance
status, TNM stage, tumor location and length. The overall response rate was 89.7%
in arm A vs. 93.5% in arm B (P>0.05). The median overall survival was 26.1 months
[95% confidence interval (CI): 15.3-36.8 months] in arm A vs. 28.7 months (95%
CI: 9.4-48.0 months) in arm B (P>0.05). Severe esophagitis occurred in 31.0%
(9/29) of the patients in arm A vs. 12.9% (4/31) of the patients in arm B; the
difference was statistically significant (P=0.036). Grade 3/4 leukopenia and
thrombocytopenia occurred in 4 (13.8%) and 1 (3.4%) patients, respectively, in
arm A vs. 12 (38.7%) and 6 (19.4%) patients, respectively, in arm B; the
differences were statistically significant (P=0.029 and 0.041, respectively).
Therefore, chemoradiotherapy with the PP regimen achieved therapeutic results
comparable with those of the PF regimen; in terms of toxicity, the incidence of
hematological toxicity was higher and that of esophagitis was lower with the PP
regimen.
PMID- 28515924
TI - Effect of serum interleukin-1 receptor antagonist level on survival of patients
with non-small cell lung cancer.
AB - Due to poor prognosis in advanced non-small cell lung cancer (NSCLC), new
effective markers are required in the monitoring of the disease. The present
study aimed to investigate the association between the serum IL-1 receptor
antagonist (IL-1Ra) level, overall survival (OS), and treatment response in
NSCLC, and to evaluate the usefulness of the serum IL-1Ra level as a prognostic
marker for NSCLC. Eighty patients (72 men and 8 women) and 40 healthy volunteers
(13 men and 27 women) were included in the present study. The median progression
free survival was 16 weeks for patients with high serum IL-1Ra levels, and 35
weeks for patients with low serum IL-1Ra levels (P=0.027). The median OS was 38
weeks in patients with a high serum IL-1Ra level, and 62 weeks in patients with a
low serum IL-1Ra level (P=0.065). The results of the present study have
demonstrated that there was a significant correlation between IL-1Ra levels and
NSCLC progression and survival, although the correlation between IL-1Ra levels
and the response to treatment was not statistically significant. Therefore, the
pre-treatment IL-1Ra level has been identified as a putative prognostic factor
for NSCLC.
PMID- 28515927
TI - Body mass index as a classifier to predict biochemical recurrence after radical
prostatectomy in patients with lower prostate-specific antigen levels.
AB - Prostate cancer, one of the most common malignant tumors among men, is closely
associated with obesity and, thus far, several studies have suggested the
association between obesity and aggressive pathological characteristics in the
United States. However, the effect of obesity on prostate cancer mortality is
controversial, and it remains unclear whether obesity contributes to the
aggressiveness of prostate cancer in Asian patients. The aim of the present study
was to investigate the association between body mass index (BMI) and the
clinicopathological characteristics of prostate cancer in 2,003 Japanese patients
who underwent radical prostatectomy. There was a significant association between
higher BMI and higher Gleason score (GS). The multivariate analysis also revealed
that BMI was an independent indicator for GS >=8 at surgery. Moreover, among
patients with lower prostate-specific antigen levels, biochemical recurrence-free
survival was significantly worse in those with higher BMI. These results suggest
that BMI may be a classifier for predicting adverse pathological findings and
biochemical recurrence after radical prostatectomy in Japanese patients.
PMID- 28515928
TI - Single-institutional experience of clinicopathological analysis and treatment for
lung cancer patients with human immunodeficiency virus infection.
AB - The advent of antiretroviral therapy has changed the disease spectrum
constitution among patients living with human immunodeficiency virus (HIV), while
the incidence of death due to non-AIDS-defining cancers, particularly lung
cancer, continues to increase in the USA and Europe. However, the availability of
detailed reports of the clinical characteristics of lung cancer among Asian
populations is limited. The present study retrospectively analyzed the clinical
characteristics, treatment regimens and outcomes of lung cancer patients with HIV
who were treated in a single institution between 1988 and 2013. Of the 20 lung
cancer patients living with HIV included in this study, 90% were diagnosed since
1996 in the post-antiretroviral era. The median CD4+ cell count was 373.5/ul,
whereas 65% of the patients were diagnosed with adenocarcinoma and 30% with
squamous cell carcinoma. Epidermal growth factor receptor mutations were detected
in 3 (27%) of the 11 specimens for which data were available, of which 65% had
advanced-stage disease. Of the 20 patients, 9 underwent surgery, 6 received
radiotherapy and 5 received chemotherapy as a first-line treatment. Treatment was
generally well-tolerated. The median survival period was 35.8 months for all
stages and 14.0 months for advanced stages. The treatment outcomes in our
institution were favorable in comparison with previous studies from the USA and
Europe, although these findings may be due to ethnic differences or the efficacy
of treatment for HIV and lung cancer.
PMID- 28515930
TI - Determination of adequate pelvic lymph node dissection range for Japanese males
undergoing radical prostatectomy.
AB - The present study aimed to determine the adequate pelvic lymph node dissection
(PLND) range for Japanese males undergoing radical prostatectomy. A total of 467
Japanese patients who underwent antegrade radical prostatectomy at the National
Kyushu Cancer Center (Fukuoka, Japan) were retrospectively reviewed. The patients
were divided into two groups according to the PLND extent: The standard
(obturator + internal iliac nodes) group and the expanded (standard + additional
nodes) group, which accounted for 64.5% (301/467) and 35.5% (166/467) of the
patients, respectively. No differences were observed in the preoperative and
postoperative characteristics of the two groups. In addition, there was no
difference in PSA recurrence between the two groups. There were no differences
between the standard and expanded groups in the low-, intermediate- and high-risk
groups (P=0.1456, P=0.1581, P=0.2125, respectively). The median number of lymph
node dissection was 13 and 19, in the standard and expanded groups respectively
(P<0.0001). However, regarding the number of lymph node metastases and the rate
of patients with lymph node metastasis, no significant difference was observed
between the standard and expanded groups (P=0.4219 and P=0.4257, respectively).
According to multivariate analysis, a significant difference in the presence of
lymph node metastasis (hazard ratio 3.547; P=0.0247), but not in the PLND extent,
was detected in patients with prostate specific antigen failure (P=0.0655). When
expanding the dissection extent, the number of dissected lymph nodes increases,
but is not associated with the number or rate of positive lymph nodes. Thus, the
current dissection range is considered to be appropriate for Japanese men
undergoing radical prostatectomy.
PMID- 28515929
TI - Clinical outcome of posterior fixation surgery in patients with vertebral
metastasis of lung cancer.
AB - Vertebral metastasis of non-small-cell lung cancer (NSCLC) often leads to
neurological paralysis, with deterioration of the patients' activities of daily
living (ADL). Surgical treatments for the symptoms are unlikely to be recommended
due to the poor prognosis of patients with advanced NSCLC. The aim of the present
study was to retrospectively evaluate the clinical outcome of posterior spinal
fixation surgery in patients with neurological paralysis resulting from vertebral
metastasis of NSCLC. Between April, 2007 and March, 2012, 4 patients (3 men and 1
woman; median age, 56.5 years) underwent fixation surgery at the Shiga University
of Medical Science Hospital (Otsu, Japan). The mean preoperative Tokuhashi and
Tomita scores of the patients were high (8.25 and 7.0, respectively). However,
the Frankel grade functional score and performance status of the patients
improved following fixation surgery, after which all patients received
chemoradiotherapy. Postoperatively, the median paralysis-free time was 41 months
(range, 17-42 months) and the median survival time was 42.5 months (range, 22-43
months). According to the functional scores, the patients had a poor prognosis,
which may have been a contraindication for fixation surgery. In these cases,
however, surgical treatment improved the patients' ADL and increased the
likelihood of receiving anticancer therapy, contributing to the prolongation of
survival. Therefore, fixation surgery may be beneficial for patients with
neurological paralysis following vertebral metastasis of advanced NSCLC.
PMID- 28515931
TI - Pharmaco-economic analysis of adjuvant chemotherapy for stage II and III
colorectal cancer.
AB - Comparison of the costs of capecitabine plus oxaliplatin (CapeOX) with that of
FOLFOX6 (5-fluorouracil/leucovorin [LV] + oxaliplatin) as an adjuvant
chemotherapy for stage II or III colorectal cancer has previously been reported.
However, there are no reports comparing uracil and tegafur (UFT)/LV with
capecitabine. Therefore, the current study compared the costs of adjuvant
chemotherapy regimens including CapeOX, FOLFOX6, capecitabine and UFT/LV. The
costs of chemotherapeutic drugs and for the prevention and treatment of adverse
events were evaluated, as these account for the bulk of the treatment costs.
Costs were expressed in Japanese Yen (US dollars). The mean costs of the
chemotherapeutic drugs per patient, for an entire course of treatment, were
Y882,632 ($8,406) for UFT/LV, Y353,290 ($3,365) for capecitabine, Y1,436,218
($13,678) for FOLFOX6 and Y1,255,630 ($11,958) for CapeOX. The mean costs
associated with adverse events per patient were Y2,210 ($21) for UFT/LV, Y6,749
($64) for capecitabine, Y173,432 ($1,652) for FOLFOX6 and Y107,430 ($1,023) for
CapeOX. Therefore, the capecitabine regimen contributes to reducing costs for the
management of patients with colorectal cancer who have had surgery.
PMID- 28515932
TI - Single-stage laparoscopic adrenalectomy for pheochromocytoma and enucleation of a
pancreatic neuroendocrine tumor in Von Hippel-Lindau disease: A case report.
AB - Von Hippel-Lindau (VHL) disease is an inherited syndrome with autosomal-dominant
transmission, characterized by central nervous system and retinal
hemangioblastomas, visceral cysts and tumors. Optimal surgical treatment,
including its timing, remains a controversial topic. The present study reports
the case of a 67-year-old female patient with adrenal and pancreatic
manifestations of VHL. A laparoscopic cortex-sparing left adrenalectomy for a 4
cm pheochromocytoma and pancreatic enucleation for pancreatic polypeptidoma of
the pancreas tail were performed during the same operative procedure. The total
operative time was 240 min. There were no operative complications, and the
surgery was completed laparoscopically with minimal blood loss. A prolonged
hospital stay was necessary to treat a grade C postoperative pancreatic fistula.
The histopathological result was an adrenal pheochromocytoma and a well
differentiated neuroendocrine tumor, secreting pancreatic polypeptides. In
conclusion, organ-sparing laparoscopic surgery is an important option for
treating simultaneous lesions in several abdominal solid viscera, such as VHL
disease, and the present case study represents, to the best of the authors'
knowledge, the first report of single-stage laparoscopic adrenalectomy and
pancreatic tumor enucleation.
PMID- 28515933
TI - Evaluation of a multiprofessional, nonsurgical obesity treatment program: which
parameters indicated life style changes and weight loss?
AB - BACKGROUND: According to the current evidence, behavior modifications are an
effective part of a non-surgical multiprofessional obesity treatment program
(MOTP). The purpose of the present study was to report changes in weight as well
in psychological variables during a one year MOTP. We aimed to identify the
associations of emotional state and patients' emotion regulation skills with
weight change. METHODS: Prospective interventional study. Data of participants
attending the one year obesity treatment in either a group or individual
structured MOTP were analyzed. Weight, BMI (Body Mass Index) and measures on
psychosomatic variables, emotion regulation skills, affective state, shame and
guilt were collected at baseline, after three months and after one year. Mixed
effects models were used for the statistical analysis of BMI. RESULTS: We
included 238 patients at baseline (t1), 234 after three months (t2) and 179 after
one year (t3). A drop in BMI measurements of at least 5% was observed in 20.6% of
participants at t2 and 41.4% of participants at t3. After three months,
participants showed significant improvements in the following psychosomatic
variables: somatisation (p < 0.001), interpersonal sensitivity (p < 0.001),
emotion regulation skills (p < 0.01), and attention to emotions (p < 0.05). Most
of the improvements could be maintained after one year. BMI reduction was
associated with a positive change in emotions, improvements in emotion regulation
skills, and a reduction of depressive symptoms, disgust and shame. CONCLUSIONS:
The results indicate that the assessment and treatment of psychological aspects
like depression, emotion regulation skills, body awareness, and acceptance should
be a vital part of an interdisciplinary MOPT. TRIAL REGISTRATION: Ethical
approval for the present study was obtained from the Bern Kantonal Ethics
Committee (KEK-Bern-Study Nr 258/14), Bern, Switzerland.
PMID- 28515934
TI - Zolpidem prescribing practices before and after Food and Drug Administration
required product labeling changes.
AB - BACKGROUND: Women have higher morning serum zolpidem concentrations than men
after taking an evening dose, potentially leading to increased risk of harm. On
19 April 2013, the United States Food and Drug Administration required labeling
changes for zolpidem, recommending an initial dose of no greater than 5 mg
(immediate release) or 6.25 mg (controlled release) per night in women.
OBJECTIVES: The primary objective of this study was to compare prescribing
practices before and after the 2013 zolpidem labeling change. A secondary
objective was to evaluate serious adverse events potentially related to zolpidem.
METHODS: Electronic medical records of adults receiving care through the
University of Colorado Health system were accessed for study inclusion if
patients were provided a first-time prescription for zolpidem either prior to or
after the Food and Drug Administration labeling change. Patients were randomly
chosen from eight strata based on age, gender, and date of zolpidem initiation
(before/after the labeling change). Demographic and zolpidem prescribing data
were collected. Low-dose zolpidem was considered 5 mg (immediate release) or 6.25
mg (controlled release) daily or less. Documentation of potentially related
serious adverse events within the patients' records was also evaluated. RESULTS:
A total of 400 patients were included in the study. The overall percentage of
patients prescribed low-dose zolpidem increased from 44% to 58% after the
labeling change (p = 0.0020). In a pre-specified subgroup analysis, the
percentage of patients prescribed low-dose zolpidem increased in all groups,
including young men (38%-50%, p = 0.23), elderly men (34%-40%, p = 0.53), and
elderly women (60%-74%, p = 0.14), but the change was only significant in young
women (42%-70%, p = 0.0045). CONCLUSION: After Food and Drug Administration
mandated labeling changes for zolpidem in 2013, the percentage of overall
patients in our health system, and specifically young women, with initial
prescriptions for low-dose zolpidem significantly increased as compared to before
the labeling change.
PMID- 28515935
TI - Methotrexate encephalopathy: Two cases in adult cancer patients, who recovered
with pathophysiologically based therapy.
AB - BACKGROUND/OBJECTIVES: Neurotoxicity is a serious and sometimes fatal adverse
effect that can occur following methotrexate treatment. We describe two adult
patients with hematological malignancies with methotrexate encephalopathy who
recovered with dextromethorphan therapy. RESULTS: Case 1: A 24-year-old male with
acute lymphoblastic leukemia developed the acute onset of bilateral facial
weakness and slurred speech after his first treatment with high-dose intravenous
methotrexate. The clinical scenario and a head magnetic resonance imaging
supported a diagnosis of methotrexate encephalopathy. Treatment with
dextromethorphan was coincident with recovery. Case 2: A 65-year-old female with
recurrent diffuse large B-cell lymphoma was treated with high-dose intravenous
methotrexate. Two weeks after a cycle, she developed hypoactive delirium, marked
lethargy, ocular ataxia, and a right-sided facial weakness. Within 2 days of
starting dextromethorphan, there was improvement with clinical recovery.
CONCLUSIONS: These two cases suggest that N-methyl d-aspartate receptor
activation by homocysteine may play an important role in the pathogenesis of
methotrexate neurotoxicity.
PMID- 28515669
TI - Suppression and azimuthal anisotropy of prompt and nonprompt [Formula: see text]
production in PbPb collisions at [Formula: see text][Formula: see text].
AB - The nuclear modification factor [Formula: see text] and the azimuthal anisotropy
coefficient [Formula: see text] of prompt and nonprompt (i.e. those from decays
of b hadrons) [Formula: see text] mesons, measured from PbPb and pp collisions at
[Formula: see text] [Formula: see text] at the LHC, are reported. The results are
presented in several event centrality intervals and several kinematic regions,
for transverse momenta [Formula: see text] [Formula: see text] and rapidity
[Formula: see text], extending down to [Formula: see text] [Formula: see text] in
the [Formula: see text] range. The [Formula: see text] of prompt [Formula: see
text] is found to be nonzero, but with no strong dependence on centrality,
rapidity, or [Formula: see text] over the full kinematic range studied. The
measured [Formula: see text] of nonprompt [Formula: see text] is consistent with
zero. The [Formula: see text] of prompt [Formula: see text] exhibits a
suppression that increases from peripheral to central collisions but does not
vary strongly as a function of either y or [Formula: see text] in the fiducial
range. The nonprompt [Formula: see text] [Formula: see text] shows a suppression
which becomes stronger as rapidity or [Formula: see text] increases. The
[Formula: see text] and [Formula: see text] of open and hidden charm, and of open
charm and beauty, are compared.
PMID- 28515936
TI - Pulse dose steroids in severe pulmonary arterial hypertension secondary to
systemic lupus erythematosus.
AB - OBJECTIVE: The pulmonary vascular targeted treatment for systemic lupus
erythematosus-associated pulmonary arterial hypertension is similar to other
connective tissue disease-associated pulmonary arterial hypertension. In
addition, there also appears to be a role for immunosuppression in the overall
management. However, the optimal immunosuppressive regimen and what patients will
respond to treatments are currently not clearly elucidated given the lack of
randomized controlled trials on the subject. Our objective is to highlight the
importance of early immunosuppression in systemic lupus erythematosus-associated
pulmonary arterial hypertension and the role of pulse dose steroids in
management. METHODS: This case describes a 23-year-old woman who presented with
pulmonary arterial hypertension diagnosed by right heart catheterization with
mean pulmonary artery pressure of 74 mmHg, pulmonary capillary wedge pressure of
12 mmHg, and a pulmonary vascular resistance of 1908 dyne s cm-5. Due to the
aggressive nature of her disease, she declined despite management with
epoprostenol and sildenafil. Because of coexisting systemic lupus erythematosus
with hemolytic anemia and worsening pulmonary arterial hypertension, intensive
immunosuppressive therapy with pulse dose steroids was initiated. RESULTS:
Shortly after initiation of pulse dose steroids and maintenance
immunosuppression, she had a dramatic symptomatic and hemodynamic response with a
decrease in her pulmonary vascular resistance from 1908 to 136 dyne sec cm-5 and
improvement in her mean pulmonary artery pressure from 74 to 27 mmHg on repeat
right heart catheterization. CONCLUSION: Early immunosuppression is important to
consider in those with systemic lupus erythematosus-associated pulmonary arterial
hypertension. Limited studies are available, but most have focused on the use of
cyclophosphamide. Pulse dose steroids may be a potentially less toxic but equally
effective manner to aid in the treatment of systemic lupus erythematosus
pulmonary arterial hypertension when intensive immunosuppression is being
considered.
PMID- 28515937
TI - Dicyano- and tetracyanopentacene: foundation of an intriguing new class of easy
to-synthesize organic semiconductors.
AB - Cyanated pentacenes are very promising candidate materials for ambipolar and n
type transistors. However, only a few examples have been obtained to date - all
requiring lengthy, multi-step processes. Herein, we present the first preparation
of 5,7,12,14-tetracyanopentacene (TCP) and a facile, scaled-up preparation of
6,13-dicyanopentacene (DCP). Both compounds are prepared by a one-pot synthesis
using cheap quinones as starting materials. Detailed crystallographic
investigations evince that the bulk assemblies of both cyanated pentacenes are
dominated by non-covalent interactions, resulting in a dense, stable, face-to
face packing and in an intriguing packing motif for TCP. Very low frontier
molecular orbital energy levels and a reversible bleaching of TCP are revealed by
cyclic voltammetry. Finally, both cyanated pentacenes are used in proof-of
concept organic thin-film transistors (OTFTs) operating under ambient conditions.
This work highlights the potential of cyanation for larger acenes and presents a
straightforward route to the rational design of this promising class of
materials.
PMID- 28515938
TI - Accounting for adjuvant-induced artifacts in the characterization of vaccine
formulations by polyacrylamide gel electrophoresis.
AB - OBJECTIVES: Several vaccine adjuvants comprise complex nano- or micro-particle
formulations, such as oil-in-water emulsions. In order to characterize
interactions and compatibility of oil-in-water emulsion adjuvants with protein
antigens in vaccines, effective protein characterization methods that can
accommodate potential interference from high concentrations of lipid-based
particles are needed. METHODS: Sodium dodecyl sulfate polyacrylamide gel
electrophoresis (SDS-PAGE) is a standard protein characterization technique which
is affected by the presence of adjuvants such as oil-in-water emulsions. In this
article, we investigate variations in SDS-PAGE methods that result in a reduction
of adjuvant-induced staining artifacts. We have investigated whether the SDS
method or the adjuvant composition were the reason for these artifacts and
succeeded in reducing the artifacts with a modified sample preparation and
different staining procedures. RESULTS: The best results were obtained by using
gold staining or silver staining instead of a Coomassie Blue staining procedure.
Moreover, the replacement of the dilution buffer (20% SDS to disrupt emulsion) by
alternative detergents such as Tween(r) 80 and Triton(r) X-100 removed adjuvant
induced streaking artifacts at the top of the gel. CONCLUSIONS: These methods may
be useful for improving characterization approaches of antigen-adjuvant mixtures
by SDS-PAGE.
PMID- 28515666
TI - Performance of algorithms that reconstruct missing transverse momentum in
[Formula: see text]= 8 TeV proton-proton collisions in the ATLAS detector.
AB - The reconstruction and calibration algorithms used to calculate missing
transverse momentum ([Formula: see text] ) with the ATLAS detector exploit energy
deposits in the calorimeter and tracks reconstructed in the inner detector as
well as the muon spectrometer. Various strategies are used to suppress effects
arising from additional proton-proton interactions, called pileup, concurrent
with the hard-scatter processes. Tracking information is used to distinguish
contributions from the pileup interactions using their vertex separation along
the beam axis. The performance of the [Formula: see text] reconstruction
algorithms, especially with respect to the amount of pileup, is evaluated using
data collected in proton-proton collisions at a centre-of-mass energy of 8
[Formula: see text] during 2012, and results are shown for a data sample
corresponding to an integrated luminosity of [Formula: see text]. The simulation
and modelling of [Formula: see text] in events containing a Z boson decaying to
two charged leptons (electrons or muons) or a W boson decaying to a charged
lepton and a neutrino are compared to data. The acceptance for different event
topologies, with and without high transverse momentum neutrinos, is shown for a
range of threshold criteria for [Formula: see text] , and estimates of the
systematic uncertainties in the [Formula: see text] measurements are presented.
PMID- 28515941
TI - Tissue-resident lymphocytes: sentinel of the transformed tissue.
AB - Tumor cells can be detected and cleared by lymphocytes in a process termed cancer
immunosurveillance. However, the contributing cell types had not been fully
characterized. Using oncogene-induced murine models of epithelial cancer, a
recent study showed that cell transformation triggers expansion of tissue
resident lymphocytes derived from innate, T cell receptor (TCR) alphabeta and
TCRgammadelta lineages. These type-1-like innate lymphoid cells (ILC1ls) and type
1 innate-like T cells (ILTC1s) share a gene expression program distinct from
those of conventional lymphocytes, and exhibit cytolytic activities against tumor
cells. Further deciphering such a tumor-elicited immunosurveillance mechanism may
1 day be harnessed for novel cancer immunotherapy.
PMID- 28515940
TI - Nivolumab-induced autoimmune diabetes mellitus presenting as diabetic
ketoacidosis in a patient with metastatic lung cancer.
AB - BACKGROUND: Advances in cancer immunotherapy have generated encouraging results
in multiple malignancies refractory to standard chemotherapies. As the use of
immune checkpoint inhibitors (ICI) proliferates, the incidence of autoimmune side
effects associated with these agents, termed immune related adverse events
(irAE), is expected to increase. The frequency of significant irAE in ICI treated
patients is about 10-20% and early recognition is critical to prevent serious
morbidity and even mortality. New onset autoimmune diabetes mellitus (DM)
associated with immune checkpoint inhibitor treatment is extremely rare,
occurring in less than 1% of patients. Autoimmune DM often presents as diabetic
ketoacidosis, a medical emergency requiring immediate treatment. We describe the
first reported case of a patient with lung cancer who developed autoimmune
diabetes after nivolumab treatment and was found to have three diabetes related
(islet) autoantibodies present before ICI treatment and seroconversion of another
after ICI treatment and onset of autoimmune DM. CASE PRESENTATION: A 34 year old
African American woman with metastatic non-small cell lung cancer (NSCLC) was
treated with nivolumab in the second line setting after disease progression
following standard chemoradiation therapy. After receiving two doses of
nivolumab, the patient developed abrupt onset of hyperglycemia and diabetic
ketoacidosis. Autoimmune diabetes was diagnosed on the basis of undetectable C
peptide levels, seropositivity of three diabetes related (islet) autoantibodies
and absolute insulin dependence. The patient eventually required use of
continuous subcutaneous insulin infusion (insulin pump) due to erratic glycemic
excursions and multiple readmissions for DKA. Human leucocyte antigen (HLA)
genoyping revealed none of the high risk haplotypes associated with the
development of type 1 diabetes. Interestingly, a frozen blood sample obtained
prior to treatment with nivolumab tested positive for three of the four diabetes
related (islet) autoantibodies despite no prior history of diabetes and no family
history of diabetes. Notably, at the time of manuscript preparation, the patient
is without evidence of NSCLC recurrence with no further treatment since the
nivolumab therapy. CONCLUSION: New onset autoimmune diabetes mellitus associated
with nivolumab has been described only in case reports and occurs at rates of <
1% in the large clinical trials which garnered FDA approval in the second line
setting for NSCLC. As ICI use continues to expand across a wide variety of
malignancies, clinicians must maintain a high index of suspicion for irAE,
including autoimmune DM and other endocrinopathies. A multidisciplinary team and
thorough education of the patient are recommended to optimize management of new
onset adult autoimmune DM. Our patient may have been at greater risk for the
development of ICI related autoimmune diabetes due to the presence of three
diabetes related autoantibodies prior to therapy; however, about half of the
reported cases of autoimmune DM after anti-PD-1 therapy occurred in patients with
no detectable diabetes related autoantibodies. Further studies are needed to
delineate genetic and immunologic biomarkers that may be useful in identifying
patients at risk of developing ICI related autoimmune DM.
PMID- 28515939
TI - Vaccine against arteriosclerosis: an update.
AB - Substantial data from experimental and clinical investigation support the role of
immune-mediated mechanisms in atherogenesis, with immune systems responding to
many endogenous and exogenous antigens that play either proatherogenic or
atheroprotective roles. An active immunization strategy against many of these
antigens could potentially alter the natural history of atherosclerosis. This
review mainly focuses on the important studies on the search for antigens that
have been tested in vaccine formulations to reduce atherosclerosis in preclinical
models. It will also address the opportunities and challenges associated with
potential clinical application of this novel therapeutic paradigm.
PMID- 28515943
TI - Evaluation of dosing strategy for pembrolizumab for oncology indications.
AB - BACKGROUND: Traditionally, most monoclonal antibodies (mAbs) have been dosed
based on body weight because of perceived contribution of body size in
pharmacokinetic variability. The same approach was used in the initial
pembrolizumab studies; however, following availability of PK data, the need for
weight-based dosing for pembrolizumab was reassessed. METHODS: A previously
established population PK (popPK) model as well as exposure-response results from
patients with advanced melanoma or non-small cell lung cancer (NSCLC) were used
to evaluate the potential application of a fixed dosing regimen with the aim of
maintaining pembrolizumab exposures within the range demonstrated to provide near
maximal efficacy and acceptable safety. Individual PK exposures for the selected
fixed dosing regimen from recently completed trials with head and neck cancer,
NSCLC, microsatellite instability high (MSI-H) in colorectal cancer (CRC) and
urothelial cancer were used to confirm acceptability. To determine whether fixed
dosing would maintain exposures within the range of clinical experience, the
individual AUC distributions with fixed dosing were compared with the range of
exposures from the pembrolizumab doses that were evaluated in early studies (2
mg/kg Q3W, 10 mg/kg Q3W/Q2W). RESULTS: Body-weight dependence of clearance was
characterized by a power relationship with an exponent of 0.578, a value
consistent with fixed- and weight-based dosing providing similar control of PK
variability. A fixed dose of 200 mg Q3W was investigated in trials based on
predicted exposures maintained within the established exposure range in all
patients. Mean (% CV, n) AUCss, 6-weeks was 1.87 (37%, 830), 1.38 (38%, 760) and
7.63 (35%, 1405) mg*day/mL in patients receiving 200 mg, 2 mg/kg and 10 mg/kg Q3W
pembrolizumab. High-weight patients had the lowest exposures with 200 mg Q3W;
however, exposures in this group (>90 kg) were within the range of prior clinical
experience at 2 mg/kg Q3W associated with near maximal efficacy. CONCLUSIONS:
Doses of 200 mg and 2 mg/kg provide similar exposure distributions with no
advantage to either dosing approach with respect to controlling PK variability.
These findings suggest that weight-based and fixed-dose regimens are appropriate
for pembrolizumab.
PMID- 28515945
TI - Exposure to occupational hazards for pregnancy and sick leave in pregnant
workers: a cross-sectional study.
AB - BACKGROUND: This study aimed to investigate the association between exposure to
occupational hazards for pregnancy and sick leave (SL) in pregnant workers.
METHODS: A cross-sectional study was performed in French occupational health
services in 2014. Occupational hazards for pregnancy were assessed by
occupational health physicians (OHPs). After delivery and at the time of
returning to work, 1,495 eligible workers were interviewed by OHPs. Information
on SL was self-reported. Risk ratios (RRs) were calculated from multivariable
analyses based on a generalized linear model with a Bernoulli distribution and a
log link adjusted for selected confounders for binary outcomes or zero-inflated
negative binomial regression for count outcomes. RESULTS: Among recruited
workers, 74.9% presented "at least one SL" during pregnancy. After adjustment,
the cumulative index of occupational hazards (0, 1-2, 3-4, >= 5 risks) for
pregnancy was significantly associated with "at least one SL" during pregnancy in
a dose-response relationship. This gradient was also observed with "early SL"
(<15 week gestation): from 1 to 2 risks, RR = 1.48 (95% confidence intervals
(CIs): 0.92-2.38); from 3 to 4 risks, RR = 2.03 (95% CI: 1.25-3.30); equal to or
higher than five risks, RR = 2.90 (95% CI: 1.89-4.44); with "duration of absence"
(adjusted mean): from 1 to 2 risks, m = 38.6 days; from 3 to 4 risks, m = 46.8
days; equal to or higher than five risks, m = 53.8 days. We also found that
deprivation, pregnancy at risk, assisted reproductive therapy, work-family
conflicts, home-work commuting felt as difficult and young age are associated
with a higher risk of SL. CONCLUSIONS: Our results support the assertion that
pregnant workers exposed to occupational hazards for pregnancy without medical
complications are also at risk of taking SL during pregnancy. More prevention in
the workplace for pregnant workers exposed to occupational hazards could reduce
SL.
PMID- 28515942
TI - A tandem CD19/CD20 CAR lentiviral vector drives on-target and off-target antigen
modulation in leukemia cell lines.
AB - BACKGROUND: Clinical success with chimeric antigen receptor (CAR)- based
immunotherapy for leukemia has been accompanied by the associated finding that
antigen-escape variants of the disease are responsible for relapse. To target
hematologic malignancies with a chimeric antigen receptor (CAR) that targets two
antigens with a single vector, and thus potentially lessen the chance of leukemic
escape mutations, a tandem-CAR approach was investigated. METHODS: Antigen
binding domains from the FMC63 (anti-CD19) and Leu16 (anti-CD20) antibodies were
linked in differing configurations to transmembrane and T cell signaling domains
to create tandem-CARs. Expression on the surface of primary human T cells was
induced by transduction with a single lentiviral vector (LV) encoding the tandem
CAR. Tandem-CARs were compared to single antigen targeting CARs in vitro and in
vivo, and to an admixture of transduced cells expressing each CAR in vivo in
immunodeficient (NSG) disease-bearing mice. RESULTS: Tandem constructs efficient
killed the Raji leukemia cell line both in vitro and in vivo. Tandem CARs
generated less cytokine than the CD20 CAR, but similar to CD19 CARs, on their
own. In co-culture experiments at low effector to target ratios with both single-
and tandem- CAR-T cells, a rapid down-modulation of full-length CD19 expression
was seen on leukemia targets. There also was a partial down-modulation of CD22,
and to a lesser degree, of CD20. Our data also highlight the extreme sensitivity
of the NALM-6 cell line to general lymphocyte-mediated cytotoxicity. While single
and tandem constructs were effective in vivo in a standard setting, in a high
disease burden setting, the tandem CAR proved both effective and less toxic than
an admixture of transduced T cell populations expressing single CARs. CONCLUSION:
Tandem CARs are equally effective in standard disease models to single antigen
specificity CARs, and may be both more effective and less toxic in a higher
disease burden setting. This may be due to optimized cell killing with more
moderate cytokine production. The rapid co-modulation of CD19, CD20, and CD22 may
account for the ability to rapidly evolve escape mutants by selecting for
leukemic clones that not require these target antigens for continued expansion.
PMID- 28515944
TI - Identifying baseline immune-related biomarkers to predict clinical outcome of
immunotherapy.
AB - As cancer strikes, individuals vary not only in terms of factors that contribute
to its occurrence and development, but as importantly, in their capacity to
respond to treatment. While exciting new therapeutic options that mobilize the
immune system against cancer have led to breakthroughs for a variety of
malignancies, success is limited to a subset of patients. Pre-existing
immunological features of both the host and the tumor may contribute to how
patients will eventually fare with immunotherapy. A broad understanding of
baseline immunity, both in the periphery and in the tumor microenvironment, is
needed in order to fully realize the potential of cancer immunotherapy. Such
interrogation of the tumor, blood, and host immune parameters prior to treatment
is expected to identify biomarkers predictive of clinical outcome as well as to
elucidate why some patients fail to respond to immunotherapy. To approach these
opportunities for progress, the Society for Immunotherapy of Cancer (SITC)
reconvened the Immune Biomarkers Task Force. Comprised of an international
multidisciplinary panel of experts, Working Group 4 sought to make
recommendations that focus on the complexity of the tumor microenvironment, with
its diversity of immune genes, proteins, cells, and pathways naturally present at
baseline and in circulation, and novel tools to aid in such broad analyses.
PMID- 28515672
TI - Measurement of prompt and nonprompt [Formula: see text] production in [Formula:
see text] and [Formula: see text] collisions at [Formula: see text].
AB - This paper reports the measurement of [Formula: see text] meson production in
proton-proton ([Formula: see text]) and proton-lead ([Formula: see text])
collisions at a center-of-mass energy per nucleon pair of [Formula: see text] by
the CMS experiment at the LHC. The data samples used in the analysis correspond
to integrated luminosities of 28[Formula: see text] and 35[Formula: see text] for
[Formula: see text] and [Formula: see text] collisions, respectively. Prompt and
nonprompt [Formula: see text] mesons, the latter produced in the decay of
[Formula: see text] hadrons, are measured in their dimuon decay channels.
Differential cross sections are measured in the transverse momentum range of
[Formula: see text], and center-of-mass rapidity ranges of [Formula: see text]
([Formula: see text]) and [Formula: see text] ([Formula: see text]). The nuclear
modification factor, [Formula: see text], is measured as a function of both
[Formula: see text] and [Formula: see text]. Small modifications to the [Formula:
see text] cross sections are observed in [Formula: see text] relative to
[Formula: see text] collisions. The ratio of [Formula: see text] production cross
sections in [Formula: see text]-going and Pb-going directions, [Formula: see
text], studied as functions of [Formula: see text] and [Formula: see text], shows
a significant decrease for increasing transverse energy deposited at large
pseudorapidities. These results, which cover a wide kinematic range, provide new
insight on the role of cold nuclear matter effects on prompt and nonprompt
[Formula: see text] production.
PMID- 28515946
TI - The responses of subjective feeling, task performance ability, cortisol and HRV
for the various types of floor impact sound: a pilot study.
AB - BACKGROUND: Recently, noise coming from the neighborhood via floor wall has
become a great social problem. The noise between the floors can be a cause of
physical and psychological problems, and the different types of floor impact
sound (FIS) may have the different effects on the human's body and mind. The
purpose of this study is to assess the responses of subjective feeling, task
performance ability, cortisol and HRV for the various types of floor impact.
METHODS: Ten men and 5 women were enrolled in our study, and the English
listening test was performed under the twelve different types of FIS, which were
made by the combinations of bang machine (B), tapping machine (T), impact ball
(I) and sound-proof mattress (M). The 15 subjects were exposed to each FIS for
about 3 min, and the subjective annoyance, performance ability (English listening
test), cortisol level of urine/saliva and heart rate variability (HRV) were
examined. The sound pressure level (SPL) and frequency of FIS were analyzed.
Repeated-measures ANOVA, paired t-test, Wilcoxon signed rank test were performed
for data analysis. RESULTS: The SPL of tapping machine (T) was reduced with the
soundproof mattress (M) by 3.9-7.3 dBA. Impact ball (I) was higher than other FIS
in low frequency (31.5-125 Hz) by 10 dBA, and tapping machine (T) was higher than
other FIS in high frequency (2-4 k Hz) by 10 dBA. The subjective annoyance is
highest in the combination of bang machine and tapping machine (BT), and next in
the tapping machine (T). The English listening score was also lowest in the BT,
and next in T. The difference of salivary cortisol levels between various types
of FIS was significant (p = 0.003). The change of HRV parameters by the change of
FIS types was significant in some parameters, which were total power (TP) (p =
0.004), low frequency (LF) (p = 0.002) and high frequency (HF) (p = 0.011).
CONCLUSIONS: These results suggest that the human's subjective and objective
responses were different according to FIS types and those combinations.
PMID- 28515952
TI - Potential role of high-stress employment in hypertension.
AB - We report a patient with a reduction in blood pressure through cessation of high
stress employment.
PMID- 28515950
TI - Factors associated with poor self-reported health within the UK military and
comparisons with the general population: a cohort study.
AB - OBJECTIVE: To investigate the self-rated health of the UK military and explore
factors associated with poor self-rated health. Compare self-rated health of the
military to the general population. DESIGN: A cohort study. PARTICIPANTS: A total
of 7626 serving and ex-serving UK military personnel, aged between 25 and 49;
19,452,300 civilians from England and Wales. SETTING: United Kingdom (military),
England and Wales (civilians). MAIN OUTCOME MEASURES: Self rated health for both
populations. Additional data for the military sample included measures of
symptoms of common mental disorder (General Health Questionnaire-12), probable
post-traumatic stress disorder (post-traumatic stress disorder checklist Civilian
Version), alcohol use (Alcohol Use Disorders Identification Test), smoking
behaviour, history of self-harm and body mass index. RESULTS: In the military
sample, poor self-rated health was significantly associated with: common mental
disorders and post-traumatic stress disorder symptomology, a history of self
harm, being obese, older age (ages 35-49) and current smoking status. However,
the majority of military personnel report good health, with levels of poor self
rated health (13%) not significantly different to those reported by the general
population (12.1%). CONCLUSIONS: Self-rated health appears to relate to aspects
of both physical and psychological health. The link between poor self-rated
health and psychological ill-health emphasises the need for military support
services to continue addressing mental health problems.
PMID- 28515948
TI - Cerebral air embolism associated with penetrating lung injury: a case report and
review of the literature.
AB - CASE: A 44-year-old man intentionally stabbed himself in the anterior neck and
left thorax with a fruit knife. Physical examination revealed two open wounds
entering the thoracic cavity in the front chest, and a stab wound entering the
trachea at the neck. Two chest tubes were initially inserted for the left lung
injury with open hemopneumothorax. Nevertheless, the worsening oxygenation
required positive pressure ventilation (PPV) with endotracheal intubation.
OUTCOME: Right hemiparesis was found during weaning from PPV. Magnetic resonance
imaging revealed multiple infarctions in the area of the bifrontal and right
temporal lobes. Cerebral air embolism (CAE) was strongly suspected from the
imaging findings and clinical course. CONCLUSION: We concluded that mechanical
ventilation was strongly involved in the occurrence of CAE. If delayed abnormal
neurological findings are observed in patients with penetrating lung injuries
receiving PPV management, CAE should be considered.
PMID- 28515953
TI - An autopsy of intravascular large B-cell lymphoma with hemophagocytic syndrome.
AB - Intravascular large B-cell lymphoma presents with highly variable symptoms caused
by the occlusion of small vessels by neoplastic cells in a variety of organs.
PMID- 28515947
TI - The impact of body armor on physical performance of law enforcement personnel: a
systematic review.
AB - BACKGROUND: The law enforcement officer profession requires performance of
arduous occupational tasks while carrying an external load, consisting of, at
minimum, a chest rig, a communication system, weaponry, handcuffs, personal
protective equipment and a torch. The aim of this systematic review of the
literature was to identify and critically appraise the methodological quality of
published studies that have investigated the impacts of body armour on task
performance and to synthesize and report key findings from these studies to
inform law enforcement organizations. METHODS: Several literature databases
(Medline, CINAHL, SPORTDiscus, EMBAS) were searched using key search words and
terms to identify appropriate studies. Studies meeting the inclusion criteria
were critically evaluated using the Downs and Black protocol with inter-rater
agreement determined by Cohen's Kappa. RESULTS: Sixteen articles were retained
for evaluation with a mean Downs and Black score of 73.2 +/- 6.8% (k = 0.841).
Based on the research quality and findings across the included studies, this
review determined that while effects of body armour on marksmanship and
physiological responses have not yet been adequately ascertained, body armour
does have significant physical performance and biomechanical impacts on the
wearer, including: a) increased ratings of perceived exertion and increased time
to complete functional tasks, b) decreased work capability (indicated by
deterioration in fitness test scores), c) decreased balance and stability, and d)
increased ground reaction forces. CONCLUSIONS: Given the physical performance and
biomechanical impacts on the wearer, body armour should be carefully selected,
with consideration of the physical fitness of the wearers and the degree to which
the armour systems can be ergonomically optimized for the specific population in
question.
PMID- 28515954
TI - A prospective cohort study of thoracic ultrasound in acute respiratory failure:
the C3PO protocol.
AB - OBJECTIVES: This study was performed to assess the clinical utility of a
standardised thoracic ultrasound examination when added to standard care in
patients with acute respiratory failure admitted to an intermediate care unit.
This study aimed to assess the impact on clinical diagnosis, clinician confidence
and management. Ultrasound has been shown to have utility in patients admitted to
intensive care and emergency; however, utility in a ward setting is unknown.
DESIGN: Prospective cohort study. SETTING: Tertiary hospital in Melbourne,
Australia. PARTICIPANTS: 50 patients with acute respiratory failure requiring
admission to an intermediate care unit. MAIN OUTCOME MEASURES: (1) Change in
clinical diagnosis or additional clinical diagnosis following thoracic
ultrasound. (2) Change in diagnostic confidence following thoracic ultrasound.
(3) Change to management following thoracic ultrasound. RESULTS: In 34% of
patients, ultrasound detected unexpected findings that changed or added to the
clinical diagnosis. Diagnostic confidence was increased in 44%, and the treating
clinician altered the management plan in 30% as a result of the ultrasound.
Ultrasound was particularly useful in clarifying the diagnosis in patients with
multiple initial diagnoses, reducing to a single diagnosis in 69%. CONCLUSIONS:
Thoracic ultrasound has clinical utility in non-intubated adults with acute
respiratory failure managed outside intensive care settings. It changed
aetiological diagnosis, increases diagnostic confidence and altered clinical
management in one out of three patients scanned. Our results suggest extended
utility of thoracic ultrasound in acute respiratory failure to a broader context
outside the intensive care unit population.
PMID- 28515955
TI - Effects of resistant dextrin for weight loss in overweight adults: a systematic
review with a meta-analysis of randomized controlled trials.
AB - BACKGROUND: Randomized controlled trials (RCTs) reported that resistant dextrin
(RD) exerted pleiotropic effects on humans. However, limited information is
available on the effects of RD for weight loss. We conducted a systematic review
with a meta-analysis to summarize the available literature and compare the
efficacy of RD for weight loss with that of a placebo in overweight adults.
METHODS: We searched the electronic databases MEDLINE, EMBASE, The Cochrane
Central Register of Controlled Trials (CENTRAL), CINAHL, Web of Science,
ClincalTrials.gov, and Japana Centra Revuo Medicina (Ichushi-web) for studies
from their onset to November 2016, and there was no language restriction. Trials
were included if they were RCTs (1) comparing the effects of RD with a placebo in
adults (18 years or older), (2) reporting body mass index, and (3) including
overweight/obese subjects as defined by the authors of RCTs. The weighted mean
difference with a 95% confidence interval (CI) was calculated using a random
effects model. RESULTS: Of the 484 studies retrieved, 3 RCTs involving 275
subjects were included in our review. The durations of RCTs ranged between 8 and
12 weeks. All RCTs were conducted in Asian countries. RD significantly improved
body mass index [mean difference -0.39 (95% CI -0.57 to -0.21) kg/m2, p < 0.01]
and body weight [mean difference -0.81 (95% CI -0.93 to -0.69) kg, p < 0.01] in
overweight adults. CONCLUSION: Our review suggests that RD exerts beneficial
effects for weight loss in overweight adults. More RCTs with different
populations and longer follow-ups are needed in order to confirm that
supplementation with RD has beneficial effects for weight loss in overweight
adults. We consider this review to provide important information for the future
submission of food with health claims.
PMID- 28515951
TI - Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and
zinc gluconate, and the role of zinc dosage.
AB - OBJECTIVE: To compare the efficacy of zinc acetate lozenges with zinc gluconate
lozenges in common cold treatment and to examine the dose-dependency of the
effect. DESIGN: Meta-analysis. SETTING: Placebo-controlled zinc lozenge trials,
in which the zinc dose was > 75 mg/day. The pooled effect of zinc lozenges on
common cold duration was calculated by using inverse-variance random-effects
method. PARTICIPANTS: Seven randomised trials with 575 participants with
naturally acquired common colds. MAIN OUTCOME MEASURE: Duration of the common
cold. RESULTS: The mean common cold duration was 33% (95% CI 21% to 45%) shorter
for the zinc groups of the seven included trials. Three trials that used lozenges
composed of zinc acetate found that colds were shortened by 40% and four trials
that used zinc gluconate by 28%. The difference between the two salts was not
significant: 12 percentage points (95% CI: -12 to + 36). Five trials used zinc
doses of 80-92 mg/day, common cold duration was reduced by 33%, and two trials
used zinc doses of 192-207 mg/day and found an effect of 35%. The difference
between the high-dose and low-dose zinc trials was not significant: 2 percentage
points (95% CI: -29 to + 32). CONCLUSIONS: Properly composed zinc gluconate
lozenges may be as effective as zinc acetate lozenges. There is no evidence that
zinc doses over 100 mg/day might lead to greater efficacy in the treatment of the
common cold. Common cold patients may be encouraged to try zinc lozenges for
treating their colds. The optimal lozenge composition and dosage scheme need to
be investigated further.
PMID- 28515949
TI - Cerebellum: An explanation for dystonia?
AB - Dystonia is a movement disorder that is characterized by involuntary muscle
contractions, abnormal movements and postures, as well as by non-motor symptoms,
and is due to abnormalities in different brain areas. In this article, we focus
on the growing number of experimental studies aimed at explaining the
pathophysiological role of the cerebellum in dystonia. Lastly, we highlight gaps
in current knowledge and issues that future research studies should focus on as
well as some of the potential applications of this research avenue. Clarifying
the pathophysiological role of cerebellum in dystonia is an important concern
given the increasing availability of invasive and non-invasive stimulation
techniques and their potential therapeutic role in this condition.
PMID- 28515958
TI - Attitudes and preferences for the clinical management of hypertension and
hypertension-related cerebrovascular disease in the general practice: results of
the Italian hypertension and brain survey.
AB - BACKGROUND: The aim of this survey was to evaluate attitudes and preferences for
the clinical management of hypertension and hypertension-related cerebrovascular
diseases (CVD) in Italy. METHODS: A predefined 16-item survey questionnaire was
anonymously administered to a large community sample of general practitioners
(GPs), trained by specialized physicians (SPs), who have been included in an
educational program between January and November 2015. RESULTS: A total of 591
physicians, among whom 48 (8%) training SPs and 543 (92%) trained GPs, provided
12,258 valid answers to the survey questionnaire. Left ventricular hypertrophy
was considered the most frequent marker of hypertension-related organ damage,
whereas atrial fibrillation and carotid atherosclerosis were considered
relatively not frequent (10-20%). The most appropriate blood pressure (BP)
targets to be achieved in hypertensive patients with CVD were <140/90 mmHg for
SPs and <135/85 mmHg for GPs. To achieve these goals, ACE inhibitors were
considered the most effective strategies by GPs, whereas SPs expressed a
preference for ARBs, both in monotherapies and in combination therapies with beta
blockers. CONCLUSIONS: This survey demonstrates that Italian physicians
considered left ventricular hypertrophy frequently associated to CVD and that
drugs inhibiting the renin-angiotensin system the most appropriate therapy to
manage hypertension and hypertension-related CVD.
PMID- 28515956
TI - Effects of phosalone consumption via feeding with or without sodium bentonite on
performance, blood metabolites and its transition to milk of Iranian Baluchi
sheep.
AB - BACKGROUND: Transfer of pesticides from environment to animal products is
inevitable, so the purpose of the present work was to evaluate phosalone
consumption via feeding with or without sodium bentonite (SB) on performance,
blood metabolites and its transition to milk of Iranian Baluchi sheep. METHODS:
Twenty Baluchi ewes were divided into four treatments (P1 as control, P2, P3, and
P4) of five animals in which phosalone, an organophosphate pesticide, was given
via diet (only for P2 and P3) at a dose of 280 mg/sheep/day for 63 consecutive
days. The SB (32 g/sheep/day; for P3 and P4) was also evaluated for its ability
to reduce deleterious effects of phosalone in the sheep diets. The control group
(P1) did not receive any phosalone and SB during the experiment. Sampling was
conducted in two periods of time including weeks 5 and 9. RESULTS: Phosalone
residues were observed in the milk samples of P2 and P3 groups during two
sampling periods. During period 1, the transfer rate of phosalone from feed to
milk was 0.23 and 0.02%, respectively for the contaminated diets (P2 and P3),
which is relatively similar to period 2 (0.22 and 0.02%). Only 0.34 (period 1)
and 0.36% (period 2) of phosalone residue are excreted in the feces of P2 group
following its daily consumption. Transfer of phosalone from feed to milk was
affected (P < 0.05) by the dietary inclusion of a commercial SB, as it (SB)
decreased excretion of phosalone via milk (P3). The phosalone and SB alone or
together had no significant effect (P > 0.05) on the dry matter intake (DMI) and
body weight (BW) gain, but feed efficiency, milk production, milk fat, dry matter
(DM) and organic matter (OM) digestibility, acetylcholinesterase (AChE)
inhibitory activity, hemoglobin (Hb), red blood cell (RBC), serum glutamic
pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT),
albumin and mean corpuscular hemoglobin concentration (MCHC) affected by the
treatments in period 1 or 2 (P < 0.05). The Hb, RBC, and MCHC were significantly
decreased (P < 0.05) by about 9.72, 20.77, and 9.71%, respectively in the group
P2 as compared to those of the control group during period 1. The AChE inhibitory
activity (period 1 and 2) significantly increased when phosalone administered via
the diet (P < 0.05). CONCLUSIONS: Although there were no adverse effects on the
performance of sheep following the intake of phosalone alone (P2 vs. P1), but
other research on the long and short times to the phosalone in high and low doses
with more animals is suggested. Overall, compared to the control group, addition
of SB in the diet of sheep improved nutrient digestibility, animal performance,
and milk health.
PMID- 28515957
TI - A psychologically informed, audiologist-delivered, manualised intervention for
tinnitus: protocol for a randomised controlled feasibility trial (Tin Man study).
AB - BACKGROUND: Chronic tinnitus is a common incurable condition often associated
with depression, anxiety, insomnia and reduced quality of life. Within National
Health Service (NHS) audiology in the United Kingdom (UK), no standard protocol
currently exists for the treatment of tinnitus. Counselling is only available in
less than half of audiology departments, and there is no agreed standard for what
constitutes tinnitus counselling. There is substantial evidence from systematic
reviews for the clinical benefit of cognitive behaviour therapy (CBT) for
tinnitus delivered by clinical psychologists or psychiatrists, but no studies
have sufficiently evidenced the NHS model of tinnitus care where management is
increasingly being delivered by audiology professionals. In a pilot randomised
controlled trial (RCT), this study aims to evaluate the feasibility of comparing
a psychologically informed guidance manual developed to support audiologist
management of tinnitus with usual treatment. METHODS/DESIGN: Phase 1 consisted of
three development stages: (1) a scoping review to generate a comprehensive set of
tinnitus counselling components, (2) a Delphi survey involving expert patients (n
= 18) and clinicians (n = 21) to establish consensus on the essential core
attributes of tinnitus counselling, and (3) incorporation of these elements into
a manualised care protocol. In phase 2, following training in a dedicated
workshop, the manualised intervention will be delivered by three experienced
audiologists across three different sites. Patients (n = 30) will be randomly
allocated to receive either (1) psychologically informed management from an
audiologist trained to deliver the manualised intervention or (2) treatment as
usual (TAU) from an audiologist who has not received this training. Quantitative
outcome measures will be administered at baseline, discharge and 6-month follow
up. Qualitative interviews with participating patients and clinicians will be
conducted to gather perspectives on the feasibility and acceptability of the
manualised intervention. DISCUSSION: The feasibility of proceeding to a
definitive RCT will be assessed via compliance with the manual, willingness to be
randomised, number of eligible participants, rate of recruitment, retention and
collection of quantitative outcome measures. This research offers an important
first step to an evidence-based, standardised and accessible approach to tinnitus
care. TRIAL REGISTRATION: ISRCTN13059163. Date of registration: 6 May 2016.
PMID- 28515962
TI - Analyses of publicly available genomics resources define FGF-2-expressing bladder
carcinomas as EMT-prone, proliferative tumors with low mutation rates and high
expression of CTLA-4, PD-1 and PD-L1.
AB - FGF-2 is overexpressed in a subset of invasive bladder carcinomas and its
overexpression correlates with poor prognosis. Analyses of publicly available
databases addressing the molecular mechanisms that may be responsible for the
poor prognosis of these tumors, revealed that FGF-2 expression correlates
positively with the expression of EMT-promoting transcription factors and with
changes in gene expression that are characteristic of EMT. The same analyses also
revealed that FGF-2 correlates negatively with the expression, mutation and copy
number variations of FGFR-3, all of which are associated with non-invasive
bladder carcinomas. Finally, they showed that FGF-2 expression correlates with
the expression of FGFR-1, the expression of the IIIc variant of FGFR-2 and with
the expression of Akt3. The latter observation is significant because our earlier
studies had shown that Akt3 regulates FGFR-2 alternative splicing, shifting the
balance toward the IIIc relative to the IIIb FGFR-2 splice variant. Since the
IIIc variant is recognized by FGF-2, while the IIIb variant is not, we conclude
that Akt3 may facilitate the FGF-2 response. FGF-2 is known to promote the
expression of KDM2B, which functions in concert with EZH2 to repress the EZH2
targeting microRNA miR-101, activating a switch, which stably upregulates EZH2.
TCGA data showing a correlation between KDM2B and EZH2 expression and Oncomine
data, showing a correlation between KDM2B and tumor progression, strongly support
the role of the FGF-2/KDM2B/miR-101/EZH2 pathway in bladder cancer. These
observations combined, suggest a model according to which FGF-2 induces EMT, cell
proliferation and cancer stem cell self-renewal by coupling the Akt3 and KDM2B
controlled pathways outlined above, in bladder carcinomas. Further analyses of
publicly-available databases, revealed that FGF-2-expressing bladder carcinomas
carry fewer genetic alterations and they tend to express high levels of CTLA-4,
PD-1 and PD-L1, which suggests immune blockade by checkpoint activation. EMT,
enhanced proliferation and immune checkpoint activation combined, may be
responsible for the poor prognosis of FGF-2-expressing bladder carcinomas.
PMID- 28515959
TI - Impact of image quality on OCT angiography based quantitative measurements.
AB - BACKGROUND: To study the impact of image quality on quantitative measurements and
the frequency of segmentation error with optical coherence tomography angiography
(OCTA). METHODS: Seventeen eyes of 10 healthy individuals were included in this
study. OCTA was performed using a swept-source device (Triton, Topcon). Each
subject underwent three scanning sessions 1-2 min apart; the first two scans were
obtained under standard conditions and for the third session, the image quality
index was reduced using application of a topical ointment. En face OCTA images of
the retinal vasculature were generated using the default segmentation for the
superficial and deep retinal layer (SRL, DRL). Intraclass correlation coefficient
(ICC) was used as a measure for repeatability. The frequency of segmentation
error, motion artifact, banding artifact and projection artifact was also
compared among the three sessions. RESULTS: The frequency of segmentation error,
and motion artifact was statistically similar between high and low image quality
sessions (P = 0.707, and P = 1 respectively). However, the frequency of
projection and banding artifact was higher with a lower image quality. The vessel
density in the SRL was highly repeatable in the high image quality sessions (ICC
= 0.8), however, the repeatability was low, comparing the high and low image
quality measurements (ICC = 0.3). In the DRL, the repeatability of the vessel
density measurements was fair in the high quality sessions (ICC = 0.6 and ICC =
0.5, with and without automatic artifact removal, respectively) and poor
comparing high and low image quality sessions (ICC = 0.3 and ICC = 0.06, with and
without automatic artifact removal, respectively). CONCLUSIONS: The frequency of
artifacts is higher and the repeatability of the measurements is lower with lower
image quality. The impact of image quality index should be always considered in
OCTA based quantitative measurements.
PMID- 28515963
TI - Eliminating Racial/Ethnic Disparities in AIDS Clinical Trials in the United
States: A Qualitative Exploration of an Efficacious Social/Behavioral
Intervention.
AB - BACKGROUND: African American/Black and Hispanic persons living with HIV (AABH
PLWH) are under-represented in AIDS clinical trials (ACTs) in the United States.
Barriers AABH-PLWH experience to ACTs are multi-faceted, including distrust of
medical research, low levels of knowledge, unsupportive social norms, lack of
referral, and challenges navigating ACT systems. In past research we found a
multi-component peer-driven intervention was efficacious in boosting rates of
screening for/enrollment into ACTs. The present qualitative study seeks to
understand AABH-PLWH's perspectives on which specific intervention features or
components had utility. Interventions features explored included structural
elements (e.g., small group sessions, individual sessions on the ACT research
unit); approaches (e.g., Motivational Interviewing); and specific components
(e.g., small-group discussion of historical and cultural factors reducing
participation among AABH-PLWH). METHODS: A total of 37 AABH-PLWH (mean age 50.6
years, SD=7.5 years; 48.6% female; 62.2% African American/Black, 27.0% Hispanic)
were purposively selected from a larger study for in-depth interviews, which were
audio-recorded, transcribed verbatim, and analyzed using systematic content
analysis. RESULTS: We found the intervention improved knowledge and positive
attitudes toward ACTs, and triggered social-level facilitators such as altruism
and more positive social norms. Discussions of cultural/historical barriers to
ACTs associated with race/ethnicity had utility. Holding a session on the ACT
research unit reduced fear and increased motivation. Results highlighted the
value of Motivational Interviewing, and several components were perceived as less
useful (e.g., involving social network members in ACT decisions). CONCLUSION:
Findings can inform future intervention designs to address racial/ethnic
disparities in ACTs and have implications for trials of other conditions where
racial/ethnic disparities persist.
PMID- 28515960
TI - Patient-Centered Network of Learning Health Systems: Developing a resource for
clinical translational research.
AB - INTRODUCTION: The Learning Health System Network clinical data research network
includes academic medical centers, health-care systems, public health
departments, and health plans, and is designed to facilitate outcomes research,
pragmatic trials, comparative effectiveness research, and evaluation of
population health interventions. METHODS: The Learning Health System Network is 1
of 13 clinical data research networks assembled to create, in partnership with 20
patient-powered research networks, a National Patient-Centered Clinical Research
Network. RESULTS AND CONCLUSIONS: Herein, we describe the Learning Health System
Network as an emerging resource for translational research, providing details on
the governance and organizational structure of the network, the key milestones of
the current funding period, and challenges and opportunities for collaborative
science leveraging the network.
PMID- 28515961
TI - Has Adolescent Childbearing Been Eclipsed by Nonmarital Childbearing?
AB - Adolescent childbearing has received decreasing attention from academics and
policymakers in recent years, which may in part reflect the decline in its
incidence. Another reason may be its uncoupling from nonmarital childbearing.
Adolescent childbearing became problematized only when it began occurring
predominantly outside marriage. In recent decades, there have been historic rises
in the rate of nonmarital childbearing, and importantly, the rise has been
steeper among older mothers than among adolescent mothers. Today, two out of five
births are to unmarried women, and the majority of these are to adults, not
adolescents. Nonmarital childbearing is in and of itself associated with lower
income and poorer maternal and child outcomes. However, unmarried adolescent
mothers might face more difficulties than unmarried adult mothers due to their
developmental status, education, living arrangements, and long-term prospects for
work. If this is true, then the focus on adolescent mothers ought to continue. We
suggest several facets of adolescent motherhood deserving of further study, and
recommend that future research use unmarried mothers in their early 20s as a
realistic comparison group.
PMID- 28515966
TI - Predicting students' happiness from physiology, phone, mobility, and behavioral
data.
AB - In order to model students' happiness, we apply machine learning methods to data
collected from undergrad students monitored over the course of one month each.
The data collected include physiological signals, location, smartphone logs, and
survey responses to behavioral questions. Each day, participants reported their
wellbeing on measures including stress, health, and happiness. Because of the
relationship between happiness and depression, modeling happiness may help us to
detect individuals who are at risk of depression and guide interventions to help
them. We are also interested in how behavioral factors (such as sleep and social
activity) affect happiness positively and negatively. A variety of machine
learning and feature selection techniques are compared, including Gaussian
Mixture Models and ensemble classification. We achieve 70% classification
accuracy of self-reported happiness on held-out test data.
PMID- 28515965
TI - Anatomic Variations of the Right Portal Vein: Prevalence, Imaging Features, and
Implications for Successful Transjugular Intrahepatic Portosystemic Shunt
Creation.
AB - Given the widespread use of transjugular intrahepatic portosystemic shunt (TIPS)
creation for the treatment of portal hypertensive complications, a working
knowledge of portal venous anatomy is critical for interventional radiologists.
The right portal vein - which is most commonly accessed during TIPS - is subject
to various anatomic variants that may potentially impact procedure success. This
pictorial essay characterizes the anatomic patterns of the right portal vein
branching in terms of type and frequency based on case series review. The work
also explains the potential procedural implications of the right portal vein
anatomic variations as they pertain to TIPS technical success.
PMID- 28515964
TI - Radiologic-Pathologic Correlation: Acellular Dermal Matrix (Alloderm(r)) Used in
Breast Reconstructive Surgery.
AB - Acellular dermal matrix (ADM) such as Alloderm(r) is sometimes used in tissue
reconstruction in primary and reconstructive breast surgeries. As ADM is
incorporated into the native tissues, the evolving imaging findings that would
correlate with varying degrees of host migration and neoangiogenesis into the
matrix can be challenging to recognize. In the setting of a palpable or clinical
area of concern after breast reconstructive surgery following breast cancer,
confident diagnosis of a mass representing ADM rather than recurring or
developing disease can be challenging. Such diagnostic imaging uncertainties
generally result in short-term imaging and clinical follow-up, but occasionally,
biopsy is performed for histopathological confirmation of benignity. A case of
biopsy-proven Alloderm(r) is described. To the best of our knowledge, this is the
first radiologic-pathologic correlation of ADM in the literature.
PMID- 28515967
TI - Unintended Pregnancies in Brazil - A Challenge for the Recommendation to Delay
Pregnancy Due to Zika.
AB - Because of the potential link between the ongoing Zika virus outbreak and a surge
in the number of cases of congenital microcephaly, officials in Latin America
have recommended that women postpone pregnancy until this association is firmly
established or the outbreak subsides. However, in all these countries a large
proportion of babies are still born out of unplanned pregnancies. Teenage girls
are particularly at high risk, as they often lack access to preventive
contraception methods, or the knowledge to use them appropriately. To gauge the
magnitude of the barriers preventing the implementation of such a recommendation
in Brazil, the country so far most affected by the Zika epidemic, we evaluated
pregnancy rates in teenage girls, and their spatial heterogeneity in the country,
in recent years (2012-2014). Nearly 20% of children born in Brazil today
(~560,000 live births) are by teenage mothers. Birth incidence is far higher in
the tropical and poorer northern states. However, in absolute terms most births
occur in the populous southeastern states, matching to a large extent the
geographic distribution of dengue (an indicator of suitable climatic and
sociodemographic conditions for the circulation of Aedes mosquitoes). These
findings indicate that recommendation to delay pregnancy will leave over half a
million pregnant adolescents in Brazil vulnerable to infection every year if not
accompanied by effective education and real access to prevention.
PMID- 28515969
TI - Application of Selective Bronchial Intubation versus Neurally Adjusted
Ventilatory Assist in the Management of Unilateral Pulmonary Interstitial
Emphysema: An Illustrative Case and the Literature Review.
AB - In the treatment of left-sided pulmonary interstitial emphysema (PIE) in a 23
week neonate, we used two ventilatory strategies: selective bronchial intubation
from day 10 to 15 and neurally adjusted ventilatory assist (NAVA) from day 18 to
26. We compared the effects and adverse effects of these two strategies. On
selective bronchial intubation, desaturation was frequent. Fentanyl infusion was
required. There was an episode of carbon dioxide retention coupled with
hypotension. On NAVA, the neonate was clinically stable without the requirement
of sedation. On selective bronchial intubation, ventilator setting in terms of
mean airway pressure and oxygen requirement was higher, which came down on the
first day of NAVA. Radiologically unilateral PIE did not resolve and became
localized in the left middle zone of lung field on selective bronchial
intubation. Also, the lobar collapse of ipsilateral, as well as contralateral
lungs occurred. On NAVA, unilateral PIE resolved. NAVA might be a good option for
the management of unilateral PIE.
PMID- 28515968
TI - How Really Ancient Is Paulinella Chromatophora?
AB - The ancestor of Paulinella chromatophora established a symbiotic relationship
with cyanobacteria related to the Prochloroccocus/Synechococcus clade. This event
has been described as a second primary endosymbiosis leading to a plastid in the
making. Based on the rate of pseudogene disintegration in the endosymbiotic
bacteria Buchnera aphidicola, it was suggested that the chromatophore in P.
chromatophora has a minimum age of ~60 Myr. Here we revisit this estimation by
using a lognormal relaxed molecular clock on the 18S rRNA of P. chromatophora.
Our time estimates show that depending on the assumptions made to calibrate the
molecular clock, P. chromatophora diverged from heterotrophic Paulinella spp. ~
90 to 140 Myr ago, thus establishing a maximum date for the origin of the
chromatophore.
PMID- 28515970
TI - TWO-DIMENSIONAL VIDEO ANALYSIS IS COMPARABLE TO 3D MOTION CAPTURE IN LOWER
EXTREMITY MOVEMENT ASSESSMENT.
AB - BACKGROUND: Although 3D motion capture is considered the "gold standard" for
recording and analyzing kinematics, 2D video analysis may be a more reasonable,
inexpensive, and portable option for kinematic assessment during pre
participation screenings. Few studies have compared quantitative measurements of
lower extremity functional tasks between 2D and 3D. PURPOSE: To compare kinematic
measurements of the trunk and lower extremity in the frontal and sagittal planes
between 2D video camera and 3D motion capture analyses obtained concurrently
during a SLS. STUDY DESIGN: Descriptive laboratory study. METHODS: Twenty-six
healthy, recreationally active adults volunteered to participate. Participants
performed three trials of the single leg squat on each limb, which were recorded
simultaneously by three 2D video cameras and a 3D motion capture system.
Dependent variables analyzed were joint displacement at the trunk, hip, knee, and
ankle in the frontal and sagittal planes during the task compared to single leg
quiet standing. RESULTS: Dependent variables exhibited moderate to strong
correlations between the two measures in the sagittal plane (r = 0.51-.093), and
a poor correlation at the knee in the frontal plane (r = 0.308) at (p <= 0.05)
All other dependent variables revealed non-significant results between the two
measures. Bland-Altman plots revealed strong agreement in the average mean
difference in the amount of joint displacement between 2D and 3D in the sagittal
plane (trunk = 1.68 o, hip = 2.60 o, knee = 0.74 o, and ankle = 3.12 o).
Agreement in the frontal plane was good (trunk = 7.92 degrees , hip = -8.72 o,
knee = -6.62 o, and ankle = 3.03 degrees ). CONCLUSION: Moderate to strong
relationships were observed between 2D video camera and 3D motion capture
analyses at all joints in the sagittal plane, and the average mean difference was
comparable to the standard error of measure with goniometry. The results suggest
that despite the lack of precision and ability to capture rotations, 2D
measurements may provide a pragmatic method of evaluating sagittal plane joint
displacement for assessing gross movement displacement and therein risk of lower
extremity injury. LEVEL OF EVIDENCE: 3.
PMID- 28515971
TI - PREDICTION OF FUNCTIONAL MOVEMENT SCREENTM PERFORMANCE FROM LOWER EXTREMITY RANGE
OF MOTION AND CORE TESTS.
AB - BACKGROUND: There are varied reports in the literature regarding the association
of the Functional Movement ScreenTM (FMSTM) with injury. The FMSTM has been
correlated with hamstring range of motion and plank hold times; however, limited
research is available on the predictability of lower extremity range of motion
(ROM) and core function on FMSTM performance. PURPOSE/HYPOTHESES: The purpose of
this study was to examine whether active lower extremity ROM measurements and
core functional tests predict FMSTM performance. The authors hypothesized that
lower extremity ROM and core functional tests would predict FMSTM composite score
(CS) and performance on individual FMSTM fundamental movement patterns. STUDY
DESIGN: Descriptive cohort study. METHODS: Forty recreationally active
participants had active lower extremity ROM measured, performed two core
functional tests, the single leg wall sit hold (SLWS) and the repetitive single
leg squat (RSLS), and performed the FMSTM. Independent t tests were used to
assess differences between right and left limb ROM measures and outcomes of core
functional tests. Linear and ordinal logistic regressions were used to determine
the best predictors of FMSTM CS and fundamental movement patterns, respectively.
RESULTS: On the left side, reduced DF and SLWS significantly predicted lower
FMSTM CS. On the right side only reduced DF significantly predicted lower FMSTM
CS. Ordinal logistic regression models for the fundamental movement patterns
demonstrated that reduced DF ROM was significantly associated with lower
performance on deep squat. Reduced left knee extension was significantly
associated with better performance in left straight leg raise; while reduced
right hip flexion was significantly associated with reduced right straight leg
raise. Lower SLWS was associated with reduced trunk stability performance.
CONCLUSIONS: FMSTM movement patterns were affected by lower extremity ROM and
core function. Researchers should consider lower FMSTM performance as indicative
of underlying issues in ROM and core function. Clinicians may consider ROM
interventions and core training strategies to improve FMSTM CS. LEVEL OF
EVIDENCE: Level 2B.
PMID- 28515972
TI - DETERMINATION OF CLINICALLY RELEVANT DIFFERENCES IN FRONTAL PLANE HOP TESTS IN
WOMEN'S COLLEGIATE BASKETBALL AND SOCCER PLAYERS.
AB - BACKGROUND: ACL injury prevention programs are less successful in female
basketball players than in soccer players. Previous authors have identified
anthropometric and biomechanical differences between the athletes and different
sport-specific demands, including a higher frequency of frontal plane activities
in basketball. Current injury risk screening and preventive training practices do
not place a strong emphasis on frontal plane activities. The medial and lateral
triple hop for distance tests may be beneficial for use in the basketball
population. HYPOTHESIS/PURPOSE: To 1) establish normative values for the medial
and lateral triple hop tests in healthy female collegiate athletes, and 2)
analyze differences in test scores between female basketball and soccer players.
It was hypothesized that due to the frequent frontal plane demands of their
sport, basketball players would exhibit greater performance during these frontal
plane performance tests. STUDY DESIGN: Cross-sectional. METHODS: Thirty-two NCAA
Division-1 female athletes (20 soccer, 12 basketball) performed three trials each
of a medial and lateral triple hop for distance test. Distances were normalized
to height and mass in order to account for anthropometric differences. Repeated
measures ANOVAs were performed to identify statistically significant main effects
of sport (basketball vs. soccer), and side (right vs. left), and sport x side
interactions. RESULTS: After accounting for anthropometric differences, soccer
players exhibited significantly better performance than basketball players in the
medial and lateral triple hop tests (p < 0.05). Significant side differences (p =
0.02) were identified in the entire population for the medial triple hop test,
such that participants jumped farther on their left (400.3 +/- 41.5 cm) than
right (387.9 +/- 43.4 cm) limbs, but no side differences were identified in the
lateral triple hop. No significant side x sport interactions were identified.
CONCLUSIONS: Women's basketball players exhibit decreased performance of frontal
plane hop tests when compared to women's soccer players. Additionally, the medial
triple hop for distance test may be effective at identifying side-to-side
asymmetries. LEVEL OF EVIDENCE: 3.
PMID- 28515976
TI - THE ACUTE EFFECTS OF CONCENTRIC VERSUS ECCENTRIC MUSCLE FATIGUE ON SHOULDER
ACTIVE REPOSITIONING SENSE.
AB - PURPOSE/BACKGROUND: Shoulder proprioception is essential in the activities of
daily living as well as in sports. Acute muscle fatigue is believed to cause a
deterioration of proprioception, increasing the risk of injury. The purpose of
this study was to evaluate if fatigue of the shoulder external rotators during
eccentric versus concentric activity affects shoulder joint proprioception as
determined by active reproduction of position. STUDY DESIGN: Quasi-experimental
trial. METHODS: Twenty-two healthy subjects with no recent history of shoulder
pathology were randomly allocated to either a concentric or an eccentric exercise
group for fatiguing the shoulder external rotators. Proprioception was assessed
before and after the fatiguing protocol using an isokinetic dynamometer, by
measuring active reproduction of position at 30 degrees of shoulder external
rotation, reported as absolute angular error. The fatiguing protocol consisted of
sets of fifteen consecutive external rotator muscle contractions in either the
concentric or eccentric action. The subjects were exercised until there was a 30%
decline from the peak torque of the subjects' maximal voluntary contraction over
three consecutive muscle contractions. RESULTS: A one-way analysis of variance
test revealed no statistical difference in absolute angular error (p > 0.05)
between concentric and eccentric groups. Moreover, no statistical difference (p >
0.05) was found in absolute angular error between pre- and post-fatigue in either
group. CONCLUSIONS: Eccentric exercise does not seem to acutely affect shoulder
proprioception to a larger extent than concentric exercise. LEVEL OF EVIDENCE:
2b.
PMID- 28515974
TI - The Effect of Fatigue on Upper Quarter Y-Balance Test Scores in Recreational
Weightlifters: A Randomized Controlled Trial.
AB - BACKGROUND: A paucity of research currently exists for upper extremity return to
sport testing. The Upper Quarter Y-Balance Test (YBT-UQ) is a clinical test of
closed kinetic chain performance with demonstrated reliability. Prior
investigations of the YBT-UQ were conducted with individuals in a resting state
and no comparison to performance in a fatigued state has been conducted. PURPOSE:
To examine the effect of upper extremity fatigue on the performance of the YBT-UQ
in recreational weightlifters. STUDY DESIGN: Randomized controlled trial.
METHODS: 24 participants who participated in recreational weight training three
days per week were randomly allocated to a control or experimental group.
Individuals in the control group were tested using the YBT-UQ and re-tested after
a 20-minute rest period. Participants in the experimental group were tested with
the YBT-UQ, performed an upper extremity exercise fatigue protocol, and
immediately re-tested. Examiners were blinded to participant allocation. RESULTS:
Differences from pre- to post-fatigue YBT-UQ testing revealed score reductions
between 2.04cm - 12.16cm for both composite scores and individual reach
directions. The repeated measures ANOVA revealed significant differences when
comparing the pre- and post-testing results between the fatigue and non-fatigue
groups for all individual directions (p <= .006) and composite scores both limbs
(p<.035). CONCLUSION: The performance of an upper body fatigue protocol
significantly reduces YBT-UQ scores in recreational weightlifters. LEVEL OF
EVIDENCE: 1b.
PMID- 28515973
TI - INTRA-RATER RELIABILITY OF THE MULTIPLE SINGLE-LEG HOP-STABILIZATION TEST AND
RELATIONSHIPS WITH AGE, LEG DOMINANCE AND TRAINING.
AB - BACKGROUND: Balance is a complex construct, affected by multiple components such
as strength and co-ordination. However, whilst assessing an athlete's dynamic
balance is an important part of clinical examination, there is no gold standard
measure. The multiple single-leg hop-stabilization test is a functional test
which may offer a method of evaluating the dynamic attributes of balance, but it
needs to show adequate intra-tester reliability. PURPOSE: The purpose of this
study was to assess the intra-rater reliability of a dynamic balance test, the
multiple single-leg hop-stabilization test on the dominant and non-dominant legs.
DESIGN: Intra-rater reliability study. METHODS: Fifteen active participants were
tested twice with a 10-minute break between tests. The outcome measure was the
multiple single-leg hop-stabilization test score, based on a clinically assessed
numerical scoring system. Results were analysed using an Intraclass Correlations
Coefficient (ICC2,1) and Bland-Altman plots. Regression analyses explored
relationships between test scores, leg dominance, age and training (an alpha
level of p = 0.05 was selected). RESULTS: ICCs for intra-rater reliability were
0.85 for the dominant and non-dominant legs (confidence intervals = 0.62-0.95 and
0.61-0.95 respectively). Bland-Altman plots showed scores within two standard
deviations. A significant correlation was observed between the dominant and non
dominant leg on balance scores (R2=0.49, p<0.05), and better balance was
associated with younger participants in their non-dominant leg (R2=0.28, p<0.05)
and their dominant leg (R2=0.39, p<0.05), and a higher number of hours spent
training for the non-dominant leg R2=0.37, p<0.05). CONCLUSIONS: The multiple
single-leg hop-stabilisation test demonstrated strong intra-tester reliability
with active participants. Younger participants who trained more, have better
balance scores. This test may be a useful measure for evaluating the dynamic
attributes of balance. LEVEL OF EVIDENCE: 3.
PMID- 28515977
TI - ESTABLISHING NORMATIVE CHANGE VALUES IN VISUAL ACUITY LOSS DURING THE DYNAMIC
VISUAL ACUITY TEST.
AB - BACKGROUND: Baseline visual acuity (VA) loss from static to dynamic head
conditions assessed using the Dynamic Visual Acuity Testing (DVAT) have not been
established in NCAA football players. DVAT assesses the Vestibulo-Ocular Reflex
(VOR) which is measured in Logarithm of the Minimum Angle of Resolution (logMAR).
Decreased VA beyond baseline measures may detect VOR impairment and impact
treatment protocols and assist in return to play decisions post-concussion.
HYPOTHESIS/PURPOSE: To establish normative VA mean scores during a static head
posture as well as dynamically during the DVAT with a head speed of 150 deg/s in
the pitch (vertical) and yaw (horizontal) planes rotating 20 degrees in each
direction. STUDY DESIGN: Descriptive study, Diagnostic Tests. METHODS: Sixty
seven, NCAA Division I College football players (age = 19.68 +/- 1.53) completed
static VA and DVAT assessment in the pitch and yaw planes during baseline
concussion testing at the beginning of the 2014 regular football season.
Comparison of VA was evaluated by calculating the difference in players' static
and dynamic VA values using the DVAT. RESULTS: Static VA for all participants
(n=67) was -0.232 +/- 0.109 logMAR. Dynamic VA for participants (n=67) was 0.0845
+/- 0.159 in pitch and -0.007 +/- 0.141 in yaw at 150 deg/sec. Mean losses in VA
during pitch and yaw at 150 deg/sec were 0.317 +/- 0.140 and 0.227 +/- 0.133,
respectively. CONCLUSIONS: VA diminishes during head movement at 150 degrees/sec.
Loss of acuity beyond established normative values from baseline may be
indicative of VOR dysfunction, especially secondary to head trauma. The
assessment of visual acuity function with head movements of 150 deg/sec can
potentially identify concussion and subsequent sequelae. Further research is
recommended. LEVEL OF EVIDENCE: 2b.
PMID- 28515978
TI - VARIATION IN MEDIAL AND LATERAL GASTROCNEMIUS MUSCLE ACTIVITY WITH FOOT POSITION.
AB - BACKGROUND: The gastrocnemius has two heads, medial gastrocnemius (MG) and
lateral gastrocnemius (LG); little is known how they contract with different foot
positions. The MG is more frequently strained than the LG; and gastrocnemius
activation pattern altered by foot position may play a role in injury. Leg
exercises often use a toe-in versus toe-out foot position to isolate one
gastrocnemius head over another. PURPOSE: The purpose of this study was to
determine the electromyographic gastrocnemius muscle activity in the toe-out and
toe-in foot positions during weight bearing and non-weight bearing activities.
The hypothesis was that a toe-out foot position would elicit greater MG than LG
activity; while the toe-in position would elicit greater activity in LG than MG
in both weight bearing and non-weight bearing (NWB) positions. STUDY DESIGN: A
cross-sectional study of young adults. METHODS: Thirty-three participants were
recruited. Surface electrodes were placed on the bellies of the MG and LG. The
gastrocnemius muscle was tested in toe-in and toe-out foot positions using two
different tests: a standing heel-rise and resisted knee flexion while prone.
Electromyographic activity was normalized against a MVIC during a heel raise with
a neutral foot position. A 2x2x2 (Foot Position x Test Position x Muscle) ANOVA
was used to determine if differences exist in activity between the MG and LG for
toe-in versus toe-out standing and prone test positions. RESULTS: Significant
test position main effect (F [1,32] = 86.9; p < .01), significant muscle main
effect (F [1,32]=5.5; p < .01), and significant foot position x muscle
interaction (F [1,32] = 14.58; p < .01) were found. Post hoc tests showed
differences between MG and LG in toe-out position (t = 3.10; p < .01) but not in
the toe-in for both test positions (t = 1.27; p = 0.21). CONCLUSIONS: With toe
out, the MG was more active than LG in standing and prone; no difference was
noted between MG and LG in toe-in for either position. LEVEL OF EVIDENCE: Level
2.
PMID- 28515979
TI - COMPARISON OF VIDEO-GUIDED, LIVE INSTRUCTED, AND SELF-GUIDED FOAM ROLL
INTERVENTIONS ON KNEE JOINT RANGE OF MOTION AND PRESSURE PAIN THRESHOLD: A
RANDOMIZED CONTROLLED TRIAL.
AB - BACKGROUND: The use of foam rollers to provide tissue massage is a commonly used
intervention by rehabilitation professionals for their patients and clients.
Currently, there is no consensus on the optimal foam rolling treatment approach.
Of particular interest are the effects of different instructional methods of foam
rolling, as individuals ultimately perform these interventions independently
outside of formal care. Finding the optimal instructional method may help improve
the individual's understanding of the technique, allowing for a safe and
effective intervention. PURPOSE: The purpose of this study was to compare the
effects of video-guided, live instructed, and self-guided foam roll interventions
on knee flexion Range of Motion (ROM) and pressure pain thresholds. METHODS:
Forty-five healthy adults were recruited and randomly allocated to one of three
intervention groups: video-guided, live-instructed, and self-guided. Each foam
roll intervention lasted a total of 2 minutes. Dependent variables included knee
flexion ROM and pressure pain threshold of the left quadriceps. Statistical
analysis included subject demographic calculations and appropriate parametric and
non-parametric tests to measure changes within and between intervention groups.
RESULTS: Each intervention group showed significant gains in knee flexion ROM (p
<= 0.003) and pressure pain thresholds (p < 0.001). An approximate 5 degree
increase of knee flexion and a 150 kPa increase in pressure pain threshold was
observed at the posttest measure for all groups. There was no significant
difference (p=0.25) found between intervention groups. CONCLUSION: All three foam
roll interventions showed short-term increases in knee flexion ROM and pressure
pain thresholds. The two instructional methods (video and live instruction) and
the self-guided method produced similar outcomes and can be used interchangeably.
Individuals can benefit from various types of instruction and in cases of limited
resources video may offer an alternative or adjunct to live instruction or an
existing self-guided program. LEVEL OF EVIDENCE: 2c.
PMID- 28515975
TI - PROSPECTIVE FUNCTIONAL PERFORMANCE TESTING AND RELATIONSHIP TO LOWER EXTREMITY
INJURY INCIDENCE IN ADOLESCENT SPORTS PARTICIPANTS.
AB - BACKGROUND: Due to the high number of adolescent athletes and subsequent lower
extremity injuries, improvements of injury prevention strategies with emphasis on
clinic-based and practical assessments are warranted. PURPOSE: The purpose of
this study was to prospectively investigate if a battery of functional
performance tests (FPT) could be used as a preseason-screening tool to identify
adolescent athletes at risk for sports-related acute lower extremity injury via
comparison of injured and uninjured subjects. METHODS: One hundred adolescent
volleyball, basketball and soccer athletes (female, n=62; male, n=38; mean age =
14.4 +/- 1.6) participated. The FPT assessment included: triple hop for distance,
star excursion balance test, double leg lowering maneuver, drop jump video test,
and multi-stage fitness test. Composite scores were calculated using a derived
equation. Subjects were monitored throughout their designated sport season(s),
which consisted of a six-month surveillance period. The schools certified
athletic trainer (ATC) recorded all injuries. Subjects were categorized into
groups according to sex and injury incidence (acute lower extremity injury vs.
uninjured) for analysis. RESULTS: Mean FPT composite scores were significantly
lower for the injured compared to the uninjured groups in both sexes (males:
19.06 +/- 3.59 vs. 21.90 +/- 2.44; females: 19.48 +/- 3.35 vs. 22.10 +/- 3.06
injured and uninjured, respectively)(p < .05). The receiver-operator
characteristic analysis determined the cut-off score at <= 20 for both genders
(sensitivity=.71, specificity=.81, for males; sensitivity=.67, specificity=.69,
for females)(p<.05) for acute noncontact lower extremity injuries. Significant
positive correlations were found between the FPT composite score and the multi
stage fitness test in male subjects (r=.474, p=.003), suggesting a relationship
between functional performance, aerobic capacity, and potential injury risk.
CONCLUSION: A comprehensive assessment of functional performance tests may be
beneficial to identify high-injury risk adolescents prior to athletic
participation.
PMID- 28515984
TI - IMPROVING THE REPORTING OF THERAPEUTIC EXERCISE INTERVENTIONS IN REHABILITATION
RESEARCH.
AB - : The foundation of evidence-based practice lies in clinical research, which is
based on the utilization of the scientific method. The scientific method requires
that all details of the experiment be provided in publications to support
replication of the study in order to evaluate and validate the results. More
importantly, clinical research can only be translated into practice when
researchers provide explicit details of the study. Too often, rehabilitation
exercise intervention studies lack the appropriate detail to allow clinicians to
replicate the exercise protocol in their patient populations. Therefore, the
purpose of this clinical commentary is to provide guidelines for optimal
reporting of therapeutic exercise interventions in rehabilitation research. LEVEL
OF EVIDENCE: 5.
PMID- 28515980
TI - INVESTIGATING THE EFFECTIVENESS OF KINESIO(r) TAPING SPACE CORRECTION METHOD IN
HEALTHY ADULTS ON PATELLOFEMORAL JOINT AND SUBCUTANEOUS SPACE.
AB - BACKGROUND: Limited quantitative, physiological evidence exists regarding the
effectiveness of Kinesio(r) Taping methods, particularly with respect to the
potential ability to impact underlying physiological joint space and structures.
To better understand the impact of these techniques, the underlying physiological
processes must be investigated in addition to the examination of more subjective
measures related to pain in unhealthy tissues. HYPOTHESIS/PURPOSE: The purpose of
this study was to determine whether the Kinesio(r) Taping Space Correction Method
created a significant difference in patellofemoral joint space, as quantified by
diagnostic ultrasound. STUDY DESIGN: Pre-test/post-test prospective cohort study.
METHODS: Thirty-two participants with bilaterally healthy knees and no past
history of surgery took part in the study. For each participant, diagnostic
ultrasound was utilized to collect three measurements: the patellofemoral joint
space, the distance from the skin to the superficial patella, and distance from
the skin to the patellar tendon. The Kinesio(r) Taping Space Correction Method
was then applied. After a ten-minute waiting period in a non-weight bearing
position, all three measurements were repeated. Each participant served as his or
her own control. RESULTS: Paired t tests showed a statistically significant
difference (mean difference = 1.1 mm, t[3,1] = 2.823, p = 0.008, g = .465)
between baseline and taped conditions in the space between the posterior surface
of the patella to the medial femoral condyle. Neither the distance from the skin
to the superficial patella nor the distance from the skin to the patellar tendon
increased to a statistically significant degree. CONCLUSIONS: The application of
the Kinesio(r) Taping Space Correction Method increases the patellofemoral joint
space in healthy adults by increasing the distance between the patella and the
medial femoral condyle, though it does not increase the distance from the skin to
the superficial patella nor to the patellar tendon. LEVEL OF EVIDENCE: 3.
PMID- 28515981
TI - A SIX-WEEK SUPERVISED EXERCISE AND EDUCATIONAL INTERVENTION AFTER TOTAL HIP
ARTHROPLASTY: A CASE SERIES.
AB - BACKGROUND AND PURPOSE: Most rehabilitation interventions after total hip
arthroplasty (THA) are not designed to return patients to high-levels of physical
activity and, thus, low levels of physical activity and residual weakness are
common. The purpose of this case series was to describe the feasibility and
preliminary efficacy of an exercise and education intervention for patients after
THA who have already completed formal outpatient physical therapy. STUDY DESIGN:
Case series. CASE DESCRIPTION: Two participants underwent unilateral THA seven
(case A) or eight (case B) months prior to the intervention. Individuals
participated in 18 treatment sessions that included progressive aerobic and
strengthening exercises and meetings with a health coach. Change in function,
strength, and self-reported physical activity were measured. Outcomes 12 months
after surgery were compared to a historical cohort of patients after THA.
OUTCOME: There were no adverse events during the intervention. At the end of the
intervention, hip and knee strength on the surgical side increased approximately
30% compared to baseline in both cases. Activity level, and recreational
performance, including walking up stairs and hiking uphill (case A), and running
and golfing (case B), improved by the end of the intervention. Most changes were
maintained at follow-up, although hip strength for case B decreased 27% after
discharge from the intervention. Outcomes for both cases exceeded historical
averages for patients 12 months after THA, with the exception of strength in case
B. DISCUSSION: The exercise intervention was well tolerated and without negative
effects in two participants. Both participants increased their ability to
complete demanding recreational and sports-related activities, physical activity,
and demonstrated improved hip abductor and knee extensor strength. Further
research is needed to evaluate the implementation and effectiveness of similar
interventions after THA. LEVEL OF EVIDENCE: Level 4.
PMID- 28515985
TI - Epidemiological trends in skin cancer.
AB - Skin cancer, including melanoma and non-melanoma skin cancer (NMSC), represents
the most common type of malignancy in the white population. The incidence rate of
melanoma is increasing worldwide, while the associated mortality remains stable,
or is slightly decreasing. On the other hand, the incidence for NMSC varies
widely, with the highest rates reported in Australia. In the current review, we
highlight recent global trends in epidemiology of skin cancer. We discuss
controversial issues raised in current epidemiological data, we analyze the most
important risk factors associated with the development of melanoma and NMSC and
the impact of skin cancer on health care services. Furthermore, we underline the
pressing need for improved registration policies, especially for NMSC, and
lastly, we refer to the ongoing primary and secondary prevention strategies and
their outcomes so far.
PMID- 28515986
TI - Use of and intentions to use dermoscopy among physicians in the United States.
AB - BACKGROUND: Dermatologists routinely use dermoscopy to improve diagnostic
accuracy of skin cancers. Much less is known about its use among other physicians
who routinely examine the skin, such as family physicians, internists and plastic
surgeons. OBJECTIVES: To document the use of dermoscopy in a sample of US
physicians and to examine physician and practice characteristics associated with
ever having used a dermascope and having some intentions to incorporate
dermoscopy into clinical practice during the next 12 months. METHODS: From
September 2015 to February 2016, we recruited 1,466 practicing physicians in
person and online to complete an anonymous survey that assessed: demographic
factors; physicians and practice characteristics; confidence differentiating skin
lesions; knowledge and use of dermoscopy; and intentions and barriers to use
dermoscopy. We conducted bivariate analysis to examine the relationship between
key factors and the outcomes and entered the significant predictors into two
separate logistic regressions. RESULTS: Fifteen percent of participants had ever
used a dermascope and 6% were currently using it. Factors significantly
associated with ever having used a dermascope (Model 1) and having intentions to
use (Model 2) at the multivariate level were: recent graduation from medical
school (strongest predictor in both models), identifying as a family physician,
seeing a higher number of patients with skin cancer and having a higher level of
confidence differentiating skin lesions. Both models were highly significant.
CONCLUSION: Use of dermoscopy was low. Promotional efforts to increase dermoscopy
use in the US are needed.
PMID- 28515988
TI - The value of pre-surgical photography in the management of melanoma.
PMID- 28515982
TI - CURRENT CONCEPTS ON THE GENETIC FACTORS IN ROTATOR CUFF PATHOLOGY AND FUTURE
IMPLICATIONS FOR SPORTS PHYSICAL THERAPISTS.
AB - CONTEXT: Recent advances within the field of genetics are currently changing many
of the methodologies in which medicine is practiced. These advances are also
beginning to influence the manner in which physical therapy services are
rendered. Rotator cuff pathology is one of the most common diagnoses treated by
the sports physical therapist. The purpose of this commentary is to educate
sports physical therapists on the recent advances regarding how genetics
influences rotator cuff pathology, including rotator cuff tears, and provide a
perspective on how this information will likely influence post-operative shoulder
rehabilitation in the near future. EVIDENCE ACQUISITION: A comprehensive review
of the literature was completed using the Medline database along with individual
searches of relevant physical therapy, surgical, cell biology, and sports
medicine journals. Search terms included: shoulder, rotator cuff pathology,
genetics, apoptosis, and physical therapy. Search results were compiled and
evaluated; relevant primary studies and review articles were gathered; the
results from this comprehensive review are summarized here. STUDY DESIGN:
Clinical Commentary, Review of the Literature. RESULTS: Recent advances within
the understanding of rotator cuff pathology have further elucidated the cellular
and molecular mechanisms associated with rotator cuff tears. There appears to be
a hypoxic-induced apoptotic cellular pathway that contributes to rotator cuff
tears. Activation of specific proteins termed matrix metalloproteinases appear to
be involved in not only primary rotator cuff tears, but also may influence the re
tear rate after surgical intervention. Further advancements in the understanding
of the cellular mechanisms contributing to rotator cuff tears and postoperative
techniques to help prevent re-tears, may soon influence the methodology in which
physical therapy services are provided to patients sustaining a rotator cuff
injury. CONCLUSIONS: At this time continued research is required to more fully
develop a comprehensive understanding of the role of genetic variables both
within primary rotator cuff tears and their influences on post-operative
rehabilitation from rotator cuff repair surgery. LEVEL OF EVIDENCE: Level 5.
PMID- 28515983
TI - A CONCEPTUAL MODEL FOR PHYSICAL THERAPISTS TREATING ATHLETES WITH PROTRACTED
RECOVERY FOLLOWING A CONCUSSION.
AB - : Sports-related concussions are receiving growing attention in healthcare. Most
concussions resolve spontaneously with little or no treatment, but twenty percent
of concussions take longer than three weeks to resolve. In some cases, symptoms
can last for five years following a traumatic brain injury. Physical Therapists
have unique skills that can assist patients experiencing protracted recovery. The
purpose of this clinical commentary is to describe a new conceptual model that
provides a framework for Physical Therapy management of patients with protracted
recovery following a sports-related concussion. The end product is a visual
diagram that represents the full scope of clinical practice that Physical Therapy
can provide to an athlete following a concussion. LEVEL OF EVIDENCE: 5.
PMID- 28515987
TI - The need for improved dermoscopy training in residency: a survey of US
dermatology residents and program directors.
AB - BACKGROUND: Inadequate dermoscopy training represents a major barrier to proper
dermoscopy use. OBJECTIVE: To better understand the status of dermoscopy training
in US residency programs. METHODS: A survey was sent to 417 dermatology residents
and 118 program directors of dermatology residency programs. RESULTS: Comparing
different training times for the same training type, residents with 1-10 hours of
dedicated training had similar confidence using dermoscopy in general (p = 1.000)
and satisfaction with training (p = .3224) than residents with >10 hours of
dedicated training. Comparing similar training times for different training
types, residents with 1-10 hours of dedicated training had significantly
increased confidence using dermoscopy in general (p = .0105) and satisfaction
with training (p = .0066) than residents with 1-10 hours of only bedside
training. Lastly, residents with 1-10 hours of dedicated training and >10 hours
of dedicated training had significantly increased confidence using dermoscopy in
general (p = .0002, p = .2471) and satisfaction with training (p <.0001, p <
.0001) than residents with no dermoscopy training at all. CONCLUSIONS: Dermoscopy
training in residency should include formal dermoscopy training that is overseen
by the program director and is possibly supplemented by outside dermoscopy
training.
PMID- 28515990
TI - Topical mycophenolate mofetil in the treatment of vitiligo: a pilot study.
AB - BACKGROUND: Vitiligo is a multifactorial disease that is characterized by
circumscribed depigmented macules and patches. Autoimmune reactions may play an
important role in the pathogenesis of the disease. Mycophenolate mofetil is a
drug that inhibits DNA synthesis in lymphocytes and has been used in autoimmune
diseases such as immunobullous skin diseases, lupus erythematosus, and autoimmune
hepatitis. OBJECTIVES: The objective of this study was to show the efficacy of
topical mycophenolate mofetil in the treatment of vitiligo. METHODS: Thirty
patients with limited vitiligo were enrolled in this study. The patients applied
a topical preparation of mycophenolate mofetil 15% twice daily for three months
and at the end of every month, repigmentation was assessed using the Vitiligo
Area Scoring Index (VASI). RESULTS: At the end of the third month, 36.6 % (n=11)
of the patients showed about 25% repigmentation of the lesions. No side effects
were observed throughout the study. CONCLUSION: This study showed that topical
mycophenolate mofetil can be somewhat effective in the treatment of vitiligo;
however, it seems to be inferior to potent topical steroids in inducing
repigmentation.
PMID- 28515989
TI - Laugier-Hunziker syndrome: a case of asymptomatic mucosal and acral
hyperpigmentation.
AB - Laugier-Hunziker syndrome (LHS) is a rare condition characterized by acquired
hyperpigmentation involving the lips, oral mucosa, acral surfaces, nails and
perineum. While patients with LHS may manifest pigmentation in all of the
aforementioned areas, most present with pigmentation localized to only a few of
these anatomical sites. We herein report a patient exhibiting the characteristic
pigment distribution pattern associated with LHS. Since LHS is a diagnosis based
on exclusion, we discuss the differential diagnosis of mucocutaneous
hyperpigmentation. Due to the benign nature of the disease, it is critical to
differentiate this disorder from conditions with similar mucocutaneous pigmentary
changes with somatic abnormalities that require medical management. We also
explore potential mechanisms that may explain the pathogenesis of LHS.
PMID- 28515991
TI - Non-follicular milky globules-dermoscopy saves the day.
AB - Acute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous
adverse reaction caused mostly by medication. Early diagnosis is important as
initiation of supportive treatment and avoidance of drug is of prime importance.
A young male presented with an erythematous rash after taking diclofenac for
pain. Polarized dermoscopy revealed milky globules on a uniform reddish
background sparing the follicles, which confirmed the diagnosis of AGEP.
PMID- 28515992
TI - Dermoscopy of cutaneous lymphangioma circumscriptum.
AB - Lymphangiomas are congenital lymphatic malformations. They are clinically
characterized by clusters of translucent vesicles, and on dermoscopy, yellow
lacunae surrounded by pale septa as well as reddish to bluish lacunae have been
described. A young male presented with a seven-year history of a vesicular
lesion. Dermoscopy revealed multiple white-yellowish well-circumscribed roundish
areas (lacunae) surrounded by pale septa. A few lacunae contained blood, which
was characteristically accumulated in the lowest part of the lacuna, resulting in
an appearance similar to the so-called "hypopyon" of the eye. We suggest a new
"dermatologic" metaphoric term to desrcibe this peculiar feature (half-and-half
lacuna).
PMID- 28515993
TI - Triage amalgamated dermoscopic algorithm (TADA) for skin cancer screening.
AB - IMPORTANCE: Dermoscopic triage algorithms have been shown to improve beginners'
abilities for identifying pigmented skin lesions requiring biopsy. OBJECTIVE: To
estimate the diagnostic accuracy of the Triage Amalgamated Dermoscopic Algorithm
(TADA) for pigmented and nonpigmented skin cancers. Secondarily, to compare TADAs
performance to those of existing triage algorithms for the identification of
pigmented skin cancers. DESIGN: Cross-sectional, observational, reader study that
took place at a beginner and intermediate level dermoscopy course. PARTICIPANTS:
Two hundred medical professionals of various specialties attended the course and
120 voluntarily joined the study (60% participation rate). EXPOSURES: After
receiving basic dermoscopy training, participants evaluated 50 polarized,
dermoscopic images of pigmented (22 benign, 18 malignant) and nonpigmented (1
benign, 9 malignant) skin lesions using TADA. Pigmented lesions were also
evaluated using the Three-Point Checklist and AC Rule. With TADA, participants
first determined if a lesion was an unequivocal angioma, dermatofibroma, or
seborrheic keratosis, which would exclude it from further evaluation. All other
lesions were assessed for architectural disorder, starburst pattern, blue-black
or gray color, shiny white structures, negative network, ulcer/erosion, or
vessels. Any one feature indicated suspicion for malignancy. RESULTS: Most
participants were dermatologists (n=64, 53.3%) or primary care physicians (n=41,
34.2%), and many lacked previous dermoscopy training (n=52, 43.3%). TADA's
sensitivity and specificity for all skin cancers was 94.6% (95% CI=93.4-95.7%)
and 72.5% (95% CI=70.1-74.7%), respectively. For pigmented skin cancers, the
sensitivity and specificity were 94.0% (95% CI=92.9-95.0%) and 75.5% (95% CI=73.8
77.2%). This compared to 71.9% (95%CI=69.8-73.9%) and 81.4% (95%CI=79.7-83.0%)
for the Three-Point Checklist and 88.6% (95%CI=87.1-89.9%) and 78.7% (95%CI=76.9
80.3%) for the AC Rule. CONCLUSIONS: These results suggest that TADA compares
favorably to existing triage algorithms and might be a useful triage tool with
high sensitivity and specificity for pigmented and nonpigmented skin cancers.
Further studies are needed to validate these preliminary observations.
PMID- 28515994
TI - In vivo reflectance confocal microscopy: a useful non-invasive tool to assess the
response to isolated limb perfusion for superficial pigmented melanoma in-transit
metastatic disease. Report of a case.
AB - Complete response can be difficult to assess after isolated limb perfusion (ILP)
for metastatic in-transit melanoma, especially when numerous and unresectable
post-necrotic persisting pigmented lesions occur. These residual lesions are
mainly seen in the more superficial and pigmented types of metastatic disease and
correspond to the residual melanophage granuloma that persists after tumor
tissues undergo complete necrosis. Reflectance confocal microscopy (RCM) is a non
invasive technique that allows the exploration of the superficial dermis. Here,
we present the case of a patient in whom numerous post-ILP limb residual
pigmented lesions were explored using combined RCM and histological examination
of sample lesions and could be characterized as non-active. This approach allowed
us to avoid additional excisions.
PMID- 28515996
TI - Dermoscopy of alopecia areata-a retrospective analysis.
AB - BACKGROUND: Dermoscopy devices can overcome the refractive properties of stratum
corneum by interface medium or cross polarization such that the lesion can be
easily seen. AIM: To examine the dermoscopic feature in alopecia areata and
correlate the severity of disease with dermoscopic features. MATERIALS AND
METHODS: Retrospective analysis of 72 patients suffering from alopecia areata
(AA), irrespective of age and sex, who visited the dermatology outpatient
department of a tertiary care center in Eastern India was carried out. The most
recently developed cases of AA were examined dermoscopically. Variables included
yellow dots (YDs), black dots (BDs), broken hair (BH), short vellus hair (SVH),
and exclamation mark hair (EMH) on the basis of available literature and
expertise. RESULTS: Yellow dots was the most common finding seen in 57 cases
(79.16%), black dots in 51 cases (70.8%). Short vellus hair was seen in 32 cases
(44.44%), broken hair was seen in 31 cases (43.05%), and exclamation mark hair in
23 cases (31.9%). YDs per field of vision was considered as the most common
finding with increased severity of AA. CONCLUSION: YDS, in increased number per
field of vision, is the most consistent finding seen in severe cases of AA, as
they are in progressive AA and alopecia universalis. An increased number of SVH
and terminal hairs were seen in patients who were being treated.
PMID- 28515995
TI - Dermoscopy and reflectance confocal microscopy in pedunculated basal cell
carcinoma.
AB - There have been limited cases of pedunculated basal cell carcinoma (BCC) reported
in the literature. The dermoscopic features were described in only one of them.
However, not one of them described the confocal microscopy features. In this
report we presented a case of pedunculated basal cell carcinoma (BCC) with
dermoscopic and reflectance confocal microscopy features.
PMID- 28515997
TI - Primary myxoid melanoma with dermoscopic findings.
AB - Myxoid melanoma is a rare variant of melanoma, which is characterized by atypical
spindle cells and dense mucin deposition in dermis. This tumor is usually seen in
elderly people with a similar progress in other variants of melanoma. A 28-year
old male presented to our outpatient clinic with a 6-month history of a slowly
growing asymptomatic pink lesion on his arm. Dermoscopic examination revealed
pink-white cristalline structures and blue-grayish ovoid globules. The lesion was
totally excised with initial diagnosis of basosquamous carcinoma, amelanotic
melanoma and basal cell carcinoma. Histopathological examination was consistent
with myxoid melanoma. We present this case due to the rarity of myxoid melanoma
and occurrence at such a young age.
PMID- 28515998
TI - Dermoscopy of histoid leprosy: a case report.
PMID- 28515999
TI - Acute onset of a severe rash on the face and dorsal hands.
PMID- 28516001
TI - Validity, Usefulness and Cost of RETeval System for Diabetic Retinopathy
Screening.
AB - PURPOSE: We studied the validity, usefulness, and relative cost to detect
diabetic retinopathy (DR) and sight-threatening DR (STDR) by using a hand-held
electrophysiologic tool compared to digital fundus photography. METHOD: Patients
with diabetes attending the screening unit of King Khaled Eye Specialist
Hospital, Riyadh, Saudi Arabia were evaluated by "RETeval", Amsler grid, and
digital dilated fundus photography. Fundus images were evaluated by a retina
specialist to determine grade of DR. The sensitivity and specificity of STDR and
DR screening compared to photography were calculated, as well as "RETeval"
combined with Amsler grid testing. The area under the curve (AUC) of "RETeval"
screening outcome was calculated. RESULT: We analyzed data of 400 diabetic
patients. The prevalence of DR of any grade was 48.8% (95% confidence interval
[CI], 43.9-53.7) while the prevalence of STDR was 27% (95% CI, 22.6-31.4). The
outcome of RETeval test was "fail" (based on 20 MUV or more amplitude of
electrophysiologic spikes) in 351 (87.8%; 95% CI, 84.5-91.0) eyes. The
sensitivity of the device was 95.4% and the specificity was 17.5%. Thus, the
sensitivity of sequential testing with RETeval and Amsler grid test was 30.1% and
the specificity was 80.1%. The AUCs for STDR and DR in general were 76.6% and
50.6%, respectively. CONCLUSIONS: "RETeval" is a rapid screening device with
excellent sensitivity for detecting STDR. It has potential as a first level
screening tool to detect patients who require further evaluation. TRANSLATIONAL
RELEVANCE: Retinal function, such as electrophysiology, can be used as a new
concept for screening for DR.
PMID- 28516002
TI - Transplantation of Human Embryonic Stem Cell-Derived Retinal Cells into the
Subretinal Space of a Non-Human Primate.
AB - PURPOSE: Previous studies have demonstrated the ability of retinal cells derived
from human embryonic stem cells (hESCs) to survive, integrate into the host
retina, and mediate light responses in murine mouse models. Our aim is to
determine whether these cells can also survive and integrate into the retina of a
nonhuman primate, Saimiri sciureus, following transplantation into the subretinal
space. METHODS: hESCs were differentiated toward retinal neuronal fates using our
previously published technique and cultured for 60 to 70 days. Differentiated
cells were further treated with 20 MUM N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S
phenylglycine t-butyl ester (DAPT) for a period of 5 days immediately prior to
subretinal transplantation. Differentiated cells were labeled with a lentivirus
expressing GFP. One million cells (10,000 cells/MUL) were injected into the
submacular space into a squirrel monkey eye, using an ab externo technique.
RESULTS: RetCam imaging demonstrated the presence and survival of human donor
cells 3 months after transplantation in the S. sciureus eye. Injected cells
consolidated in the temporal macula. GFP+ axonal projections were observed to
emanate from the central consolidation of cells at 1 month, with some projecting
into the optic nerve by 3 months after transplantation. CONCLUSIONS: Human ES
cell-derived retinal neurons injected into the submacular space of a squirrel
monkey survive at least 3 months postinjection without immunosuppression. Some
donor cells appeared to integrate into the host inner retina, and numerous donor
axonal projections were noted throughout, with some projecting into the optic
nerve. TRANSLATIONAL RELEVANCE: These data illustrate the feasibility of hESC
derived retinal cell replacement in the nonhuman primate eye.
PMID- 28516000
TI - Role of a Dual Splicing and Amino Acid Code in Myopia, Cone Dysfunction and Cone
Dystrophy Associated with L/M Opsin Interchange Mutations.
AB - PURPOSE: Human long (L) and middle (M) wavelength cone opsin genes are highly
variable due to intermixing. Two L/M cone opsin interchange mutants, designated
LIAVA and LVAVA, are associated with clinical diagnoses, including red-green
color vision deficiency, blue cone monochromacy, cone degeneration, myopia, and
Bornholm Eye Disease. Because the protein and splicing codes are carried by the
same nucleotides, intermixing L and M genes can cause disease by affecting
protein structure and splicing. METHODS: Genetically engineered mice were created
to allow investigation of the consequences of altered protein structure alone,
and the effects on cone morphology were examined using immunohistochemistry. In
humans and mice, cone function was evaluated using the electroretinogram (ERG)
under L/M- or short (S) wavelength cone isolating conditions. Effects of LIAVA
and LVAVA genes on splicing were evaluated using a minigene assay. RESULTS: ERGs
and histology in mice revealed protein toxicity for the LVAVA but not for the
LIAVA opsin. Minigene assays showed that the dominant messenger RNA (mRNA) was
aberrantly spliced for both variants; however, the LVAVA gene produced a small
but significant amount of full-length mRNA and LVAVA subjects had correspondingly
reduced ERG amplitudes. In contrast, the LIAVA subject had no L/M cone ERG.
CONCLUSIONS: Dramatic differences in phenotype can result from seemingly minor
differences in genotype through divergent effects on the dual amino acid and
splicing codes. TRANSLATIONAL RELEVANCE: The mechanism by which individual
mutations contribute to clinical phenotypes provides valuable information for
diagnosis and prognosis of vision disorders associated with L/M interchange
mutations, and it informs strategies for developing therapies.
PMID- 28516005
TI - Caffey's Disease Sans Mandibular and Clavicular Involvement: A Rare Case Report.
AB - Caffey's disease, also known as Infantile Cortical Hyperostosis, is a rare, self
limited, benign, inflammatory gene-related disorder of infants that causes bone
changes, soft tissue swelling, and irritability. The mandible (75%), clavicles,
and ulnae are the bones most frequently involved, others being long bones,
lateral ribs, ilia with skull being the rarest. However, we report a case of a 5
month-old male diagnosed with Infantile cortical hyperostosis but with absent
mandibular and clavicular involvement, thus depicting the unusual presentation of
this disease.
PMID- 28516004
TI - Endoscopic Ultrasound: Reaching Where Others Can't.
AB - Endoscopic ultrasound (EUS) has been increasingly used for the diagnosis and
staging of pancreatic cancer. It has recently become the modality of choice in
assessing pancreatic lesions overcoming other traditional modalities. Typically
lesions located at the tail of the pancreas are best accessed through the
stomach. We present a patient with pancreatic tail mass occurring in the setting
of a large hiatal hernia, intrathoracic stomach, and severe lumbar levoscoliosis.
Due to altered anatomy and extensive vascular connections of the mass, any
surgical or radiological intervention was considered high risk for the patient.
EUS was the only modality capable of providing a pancreatic mass tissue sample in
this patient with challenging thoraco-abdominal anatomy. Moreover, pancreatic
tail lesions are traditionally best accessed through the gastric fundus; however,
in view of the patient's altered anatomy, EUS-fine needle aspiration (FNA) had to
be performed through the duodenum. This case raises the importance of EUS when
surgical and radiological interventions are restricted.
PMID- 28516003
TI - Mode of action of the 2-phenylquinoline efflux inhibitor PQQ4R against
Escherichia coli.
AB - Efflux pump inhibitors are of great interest since their use as adjuvants of
bacterial chemotherapy can increase the intracellular concentrations of the
antibiotics and assist in the battle against the rising of antibiotic-resistant
bacteria. In this work, we have described the mode of action of the 2
phenylquinoline efflux inhibitor (4-(2-(piperazin-1-yl)ethoxy)-2-(4
propoxyphenyl) quinolone - PQQ4R), against Escherichia coli, by studding its
efflux inhibitory ability, its synergistic activity in combination with
antibiotics, and compared its effects with the inhibitors phenyl-arginine-beta
naphthylamide (PAbetaN) and chlorpromazine (CPZ). The results showed that PQQ4R
acts synergistically, in a concentration dependent manner, with antibiotics known
to be subject to efflux in E. coli reducing their MIC in correlation with the
inhibition of their efflux. Real-time fluorometry assays demonstrated that PQQ4R
at sub-inhibitory concentrations promote the intracellular accumulation of
ethidium bromide inhibiting its efflux similarly to PAbetaN or CPZ, well-known
and described efflux pump inhibitors for Gram-negative bacteria and whose
clinical usage is limited by their levels of toxicity at clinical and
bacteriological effective concentrations. The time-kill studies showed that
PQQ4R, at bactericidal concentrations, has a rapid antimicrobial activity
associated with a fast decrease of the intracellular ATP levels. The results also
indicated that the mode of action of PQQ4R involves the destabilization of the E.
coli inner membrane potential and ATP production impairment, ultimately leading
to efflux pump inhibition by interference with the energy required by the efflux
systems. At bactericidal concentrations, membrane permeabilization increases and
finally ATP is totally depleted leading to cell death. Since drug resistance
mediated by the activity of efflux pumps depends largely on the proton motive
force (PMF), dissipaters of PMF such as PQQ4R, can be regarded as future
adjuvants of conventional therapy against E. coli and other Gram-negative
bacteria, especially their multidrug resistant forms. Their major limitation is
the high toxicity for human cells at the concentrations needed to be effective
against bacteria. Their future molecular optimization to improve the efflux
inhibitory properties and reduce relative toxicity will optimize their potential
for clinical usage against multi-drug resistant bacterial infections due to
efflux.
PMID- 28516006
TI - Hydrogel formation by multivalent IDPs: A reincarnation of the microtrabecular
lattice?
AB - Based on high-voltage electron microscopic (HVEM) data of fixed cultured cells,
an elaborate three-dimensional network of filaments, including and
interconnecting other elements of the cytoskeleton, was observed in cells some
half a century ago. Despite many attempts and comparative studies, this
"microtrabecular lattice" (MTL) of the cytoplasmic ground substance could not be
established as a genuine component of the eukaryotic cell, and is mostly
considered today as a sample-preparation artifact of protein adherence and cross
linking to the cytoskeleton. Here we elaborate on the provocative idea that
recent observations of hydrogel-forming phase transitions of repetitive regions
of intrinsically disordered proteins (IDPs) bear resemblance in creation,
organization and physical appearance to the MTL. We review this phenomenon in
detail, and suggest that phase transitions of actin regulatory proteins,
neurofilament side-arms and other proteins could generate non-uniform spatial
distribution of cytoplasmic material in the vicinity of the cytoskeleton that
might even give rise to fixation phenomena resembling the MTL. Whether such
hydrogel formation by IDPs is a general physical phenomenon, will remain to be
seen, nevertheless, the underlying organizational principle provokes novel
experimental studies to uncover the ensuing higher-level regulation of cell
physiology, in which the despised and long-forgotten concept of MTL might give
some interesting leads.
PMID- 28516007
TI - What's in a name? Why these proteins are intrinsically disordered: Why these
proteins are intrinsically disordered.
AB - "What's in a name? That which we call a rose By any other name would smell as
sweet." From "Romeo and Juliet", William Shakespeare (1594) This article opens a
series of publications on disambiguation of the basic terms used in the field of
intrinsically disordered proteins. We start from the beginning, namely from the
explanation of what the expression "intrinsically disordered protein" actually
means and why this particular term has been chosen as the common denominator for
this class of proteins characterized by broad structural, dynamic and functional
characteristics.
PMID- 28516009
TI - MFDp2: Accurate predictor of disorder in proteins by fusion of disorder
probabilities, content and profiles.
AB - Intrinsically disordered proteins (IDPs) are either entirely disordered or
contain disordered regions in their native state. IDPs were found to be abundant
in complex organisms and implicated in numerous cellular processes. Experimental
annotation of disorder lags behind the rapidly growing sizes of the protein
databases, and thus computational methods are used to close this gap and to
investigate the disorder. MFDp2 is a novel content-rich and user-friendly web
server for sequence-based prediction of protein disorder that builds upon our
residue-level disorder predictor MFDp and chain-level disorder content predictor
DisCon. It applies novel post-processing filters and uses sequence alignment to
improve predictive quality. Using a new benchmark data set, which has reduced
sequence identity to corresponding training data sets, MFDp2 is shown to provide
competitive predictive quality when compared with MFDp and a comprehensive set of
13 other state-of-the-art predictors, including publicly available versions of
the top predictors from CASP9. Our server obtains the highest Mathews Correlation
Coefficient (MCC) and the second best Area Under the receiver operating
characteristic Curve (AUC). In addition to the disorder predictions, our server
also outputs well-described sequence-derived information that allows profiling
the predicted disorder. We conveniently visualize sequence conservation,
predicted secondary structure, relative solvent accessibility and alignments to
chains with annotated disorder. We allow predictions for multiple proteins at the
same time and each prediction can be downloaded as text-based (parsable) file.
The web server, which includes help pages and tutorial, is freely available at
biomine.ece.ualberta.ca/MFDp2/.
PMID- 28516008
TI - The alphabet of intrinsic disorder: I. Act like a Pro: On the abundance and roles
of proline residues in intrinsically disordered proteins.
AB - A significant fraction of every proteome is occupied by biologically active
proteins that do not form unique three-dimensional structures. These
intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) have essential
biological functions and are characterized by extensive structural plasticity.
Such structural and functional behavior is encoded in the amino acid sequences of
IDPs/IDPRs, which are enriched in disorder-promoting residues and depleted in
order-promoting residues. In fact, amino acid residues can be arranged according
to their disorder-promoting tendency to form an alphabet of intrinsic disorder
that defines the structural complexity and diversity of IDPs/IDPRs. This review
is the first in a series of publications dedicated to the roles that different
amino acid residues play in defining the phenomenon of protein intrinsic
disorder. We start with proline because data suggests that of the 20 common amino
acid residues, this one is the most disorder-promoting.
PMID- 28516011
TI - Functional fragments of disorder in outer membrane beta barrel proteins.
AB - The traditional view of "sequence-structure-function" has been amended by the
discovery of intrinsically disordered proteins. Almost 50% of PDB structures are
now known to have one or more regions of disorder, which are involved in diverse
functions. These regions typically possess low aromatic content and sequence
complexity as well as high net charge and flexibility. In this study, we examined
the composition and contribution of intrinsic disorder in outer membrane beta
barrel protein functions. Our systematic analysis to find the dual personality
(DP) fragments, which often function by disorder-order transitions, revealed the
presence of 61 DP fragments with 234 residues in beta barrel trans membrane
protein structures. It was found that though the disorder is more prevalent in
the periplasmic regions, most of the residues which undergo disorder-order
transitions are found in the extracellular regions. For example, the calcium
binding sites in BtuB protein are found to undergo disorder to order transition
upon binding calcium. The conformational change in the cell receptor binding site
of the OpcA protein, which is important in host cell interactions of N.
meningitidis, was also found to be due to the disorder-order transitions
occurring in the presence of the ligand. The natively disordered nature of DP
fragments makes it more appropriate to call them "functional fragments of
disorder." The present study provides insight into the roles played by
intrinsically disordered regions in outer membrane protein functions.
PMID- 28516013
TI - SS-map: Visualizing cooperative secondary structure elements in protein
ensembles.
AB - We present SS-map, a tool to visualize the secondary structure content of
ensembles of proteins. When generating ensembles of intrinsically disordered
proteins, we lose the understanding a single native structure gives for folded
proteins. It then becomes difficult to visualize the composition of the ensembles
or to detect transient helices such as MoRFs. Conformational propensities for
single residues also hide the nature of cooperative structures. Here we show how
SS-map describes folded and unfolded ensembles of some peptides and gives a new
view of the ensembles used to describe intrinsically disordered proteins with
residual structure in computational and NMR experiments. This tool is implemented
in an open-source python code located at code.google.com/p/ss-map.
PMID- 28516014
TI - A method to trap transient and weak interacting protein complexes for structural
studies.
AB - Several key biological events adopt a "hit-and-run" strategy in their transient
interactions between binding partners. In some instances, the disordered nature
of one of the binding partners severely hampers the success of co
crystallization, often leading to the crystallization of just one of the
partners. Here, we discuss a method to trap weak and transient protein
interactions for crystallization. This approach requires the structural details
of at least one of the interacting partners and binding knowledge to dock the
known minimum binding region (peptide) of the protein onto the other using an
optimal-sized linker. Prior to crystallization, the purified linked construct
should be verified for its intact folding and stability. Following structure
determination, structure-guided functional studies are performed with
independent, full-length unlinked proteins to validate the findings of the linked
complex. We designed this approach and then validated its efficacy using a 24
amino acid minimum binding region of the intrinsically disordered, neuron
specific substrates, Neurogranin and Neuromodulin, joined via a Gly-linker to
their interacting partner, Calmodulin. Moreover, the reported functional studies
with independent full-length proteins confirmed the findings of the linked
peptide complexes. Based on our studies, and in combination with the supporting
literature, we suggest that optimized linkers can provide an environment to mimic
the natural interactions between binding partners, and offer a useful strategy
for structural studies to trap weak and transient interactions involved in
several biological processes.
PMID- 28516010
TI - The alphabet of intrinsic disorder: II. Various roles of glutamic acid in ordered
and intrinsically disordered proteins.
AB - The ability of a protein to fold into unique functional state or to stay
intrinsically disordered is encoded in its amino acid sequence. Both ordered and
intrinsically disordered proteins (IDPs) are natural polypeptides that use the
same arsenal of 20 proteinogenic amino acid residues as their major building
blocks. The exceptional structural plasticity of IDPs, their capability to exist
as heterogeneous structural ensembles and their wide array of important disorder
based biological functions that complements functional repertoire of ordered
proteins are all rooted within the peculiar differential usage of these building
blocks by ordered proteins and IDPs. In fact, some residues (so-called disorder
promoting residues) are noticeably more common in IDPs than in sequences of
ordered proteins, which, in their turn, are enriched in several order-promoting
residues. Furthermore, residues can be arranged according to their "disorder
promoting potencies," which are evaluated based on the relative abundances of
various amino acids in ordered and disordered proteins. This review continues a
series of publications on the roles of different amino acids in defining the
phenomenon of protein intrinsic disorder and concerns glutamic acid, which is the
second most disorder-promoting residue.
PMID- 28516016
TI - Structural characterizations of phosphorylatable residues in transmembrane
proteins from Arabidopsis thaliana.
AB - Phosphorylation is a common post-translational modification that plays important
roles in a wide range of biochemical and cellular processes. Many enzymes and
receptors can be switched "on" or "off" by conformational changes induced by
phosphorylation. The phosphorylation process is mediated by a family of enzymes
called kinase. Currently, more than 1,000 different kinases have been identified
in Arabidopsis thaliana proteome. Kinases interact with each other and with many
regulatory proteins forming phosphorylation networks. These phosphorylation
networks modulate the signaling processes and control the functions of cells.
Normally, kinases phosphorylate serines, threonines, and tyrosines. However, in
many proteins, not all of these 3 types of amino acids can be phosphorylated.
Therefore, identifying the phosphorylation sites and the possible phosphorylation
events is very important in decoding the processes of regulation and the function
of phosphorylation networks. In this study, we applied computational and
bioinformatics tools to characterize the association between phosphorylation
events and structural properties of corresponding proteins by analyzing more than
50 trans-membrane proteins from Arabidopsis thaliana. In addition to the
previously established conclusion that phosphorylation sites are closely
associated with intrinsic disorder, we found that the phosphorylation process may
also be affected by solvent accessibility of phosphorylation sites and further
promoted by neighboring modification events.
PMID- 28516012
TI - Extracting structural information from charge-state distributions of
intrinsically disordered proteins by non-denaturing electrospray-ionization mass
spectrometry.
AB - Intrinsically disordered proteins (IDPs) exert key biological functions but tend
to escape identification and characterization due to their high structural
dynamics and heterogeneity. The possibility to dissect conformational ensembles
by electrospray-ionization mass spectrometry (ESI-MS) offers an attracting
possibility to develop a signature for this class of proteins based on their
peculiar ionization behavior. This review summarizes available data on charge
state distributions (CSDs) obtained for IDPs by non-denaturing ESI-MS, with
reference to globular or chemically denatured proteins. The results illustrate
the contributions that direct ESI-MS analysis can give to the identification of
new putative IDPs and to their conformational investigation.
PMID- 28516015
TI - Digested disorder: Quarterly intrinsic disorder digest (January/February/March,
2013).
AB - The current literature on intrinsically disordered proteins is blooming. A simple
PubMed search for "intrinsically disordered protein OR natively unfolded protein"
returns about 1,800 hits (as of June 17, 2013), with many papers published quite
recently. To keep interested readers up to speed with this literature, we are
starting a "Digested Disorder" project, which will encompass a series of reader's
digest type of publications aiming at the objective representation of the
research papers and reviews on intrinsically disordered proteins. The only two
criteria for inclusion in this digest are the publication date (a paper should be
published within the covered time frame) and topic (a paper should be dedicated
to any aspect of protein intrinsic disorder). The current digest covers papers
published during the period of January, February and March of 2013. The papers
are grouped hierarchically by topics they cover, and for each of the included
paper a short description is given on its major findings.
PMID- 28516019
TI - Hydrogen skeleton, mobility and protein architecture.
AB - The mobility of the proton-proton radial vectors is introduced as a quantitative
measure for the structural dynamics of organic materials, especially protein
molecules. As defined for the entire molecule, the hydrogen mobility (HM) is
proposed as an "order parameter," which describes the effect of motional
narrowing on inter-proton dipole-dipole interactions. HM satisfies all
requirements of an order parameter in the Landau molecular field theory of phase
transitions. The wide-line NMR second moments needed to obtain HM are exactly
defined and measurable physical quantities, which are not produced by
mathematical fitting and do not carry the limitations and restrictions of any
model (theoretical formalism). We first demonstrate the usefulness of HM on small
organic molecules with data taken form the literature. We outline its link with
structural and functional characteristics on a range of proteins: HM provides a
model-free parameter based on first principles that can clearly distinguish
between globular and intrinsically disordered proteins, and can also provide
insight into the behavior of disease-related mutants.
PMID- 28516020
TI - Understanding the molecular mechanisms underlying complex cancer genome
rearrangements.
AB - In their recent paper, Malhotra et al. performed a comprehensive analysis of the
structural variation breakpoints in 64 cancer genomes from 7 tumor types to find
the prevalence and origins of complex genomic rearrangements.1 Since this work
represents a breakthrough in understanding of the molecular mechanisms underlying
complex cancer genome rearrangements, we provide a brief overview of this
outstanding study.
PMID- 28516017
TI - Distribution and cluster analysis of predicted intrinsically disordered protein
Pfam domains.
AB - The Pfam database groups regions of proteins by how well hidden Markov models
(HMMs) can be trained to recognize similarities among them. Conservation pressure
is probably in play here. The Pfam seed training set includes sequence and
structure information, being drawn largely from the PDB. A long standing
hypothesis among intrinsically disordered protein (IDP) investigators has held
that conservation pressures are also at play in the evolution of different kinds
of intrinsic disorder, but we find that predicted intrinsic disorder (PID) is not
always conserved across Pfam domains. Here we analyze distributions and clusters
of PID regions in 193024 members of the version 23.0 Pfam seed database. To
include the maximum information available for proteins that remain unfolded in
solution, we employ the 10 linearly independent Kidera factors1-3 for the amino
acids, combined with PONDR4 predictions of disorder tendency, to transform the
sequences of these Pfam members into an 11 column matrix where the number of rows
is the length of each Pfam region. Cluster analyses of the set of all regions,
including those that are folded, show 6 groupings of domains. Cluster analyses of
domains with mean VSL2b scores greater than 0.5 (half predicted disorder or more)
show at least 3 separated groups. It is hypothesized that grouping sets into
shorter sequences with more uniform length will reveal more information about
intrinsic disorder and lead to more finely structured and perhaps more accurate
predictions. HMMs could be trained to include this information.
PMID- 28516018
TI - Hypothesis: The unfolding power of protein dielectricity.
AB - A hypothesis is proposed on a potential role of protein dielectricity as an
unfolding factor in protein-protein interactions. It is suggested that large
protein complexes and aggregation seeds can unfold target proteins by virtue of
their effect on the dielectric properties of water at the protein-solvent
interface. Here, similar to the effect of membrane surfaces, protein surface can
cause decrease in the local dielectric constant of solvent and thereby induce
structural changes in a target protein approaching this surface. Some potential
implementations of this hypothetical mechanism are also discussed.
PMID- 28516022
TI - A NAD(P) reductase like protein is the salicylic acid receptor in the appendix of
the Sauromatum guttatum inflorescence.
AB - The mode of action of the thermogenic inducers (salicylic acid, aspirin, and 2,6
dihydroxybenzoic acid) in the appendix of the Sauromatum guttatum inflorescence
is poorly understood. Using ESI-MS and light scattering analysis, we have
demonstrated that NAD(P) reductase like protein (RL) is the salicylic acid
receptor in the Sauromatum appendix. RL was self-assembled in water into a large
unit with a hydrodynamic diameter of 800 nm. In the presence of 1 pM salicylic
acid, RL exhibited discontinuous and reversible volume phase transitions. The
volume phase changed from 800 to 300 nm diameter and vice versa. RL stayed at
each volume phase for ~4-5 min with a fast relaxation time between the 2 phases.
ESI-MS analysis of RL extracted from appendices treated with salicylic acid,
aspirin, and 2,6-DHBA at a micromolar range demonstrated that these compounds are
capable of inducing graded conformational changes that are concentration
dependent. A strong correlation between RL conformations and heat-production
induced by salicylic acid was also observed. These preliminary findings reveal
structural and conformational roles for RL by which plants regulate their
temperature and synchronize their time keeping mechanisms.
PMID- 28516021
TI - Multiple fuzzy interactions in the moonlighting function of thymosin-beta4.
AB - Thymosine beta4 (Tbeta4) is a 43 amino acid long intrinsically disordered protein
(IDP), which was initially identified as an actin-binding and sequestering
molecule. Later it was described to have multiple other functions, such as
regulation of endothelial cell differentiation, blood vessel formation, wound
repair, cardiac cell migration, and survival.1 The various functions of Tbeta4
are mediated by interactions with distinct and structurally unrelated partners,
such as PINCH, ILK, and stabilin-2, besides the originally identified G-actin.
Although the cellular readout of these interactions and the formation of these
complexes have been thoroughly described, no attempt was made to study these
interactions in detail, and to elucidate the thermodynamic, kinetic, and
structural underpinning of this range of moonlighting functions. Because Tbeta4
is mostly disordered, and its 4 described partners are structurally unrelated
(the CTD of stabilin-2 is actually fully disordered), it occurred to us that this
system might be ideal to characterize the structural adaptability and ensuing
moonlighting functions of IDPs. Unexpectedly, we found that Tbeta4 engages in
multiple weak, transient, and fuzzy interactions, i.e., it is capable of
mediating distinct yet specific interactions without adapting stable folded
structures.
PMID- 28516024
TI - Disorder in the lifetime of a protein.
AB - Intrinsic disorder is everywhere and is inevitable. The non-folding propensity is
inherent for numerous natural polypeptide chains, and many functional proteins
and protein regions are intrinsically disordered. Furthermore, at particular
moments in their life, most notably during their synthesis and degradation, all
ordered proteins are at least partially unfolded (disordered). Also, there is a
widely spread phenomenon of conditional (functional or transient) disorder, where
functions of many ordered proteins require local or even global unfolding of
their unique structures. Finally, extrinsic disorder (i.e., intrinsic disorder in
functional partners of ordered proteins) should be taken into account too.
Therefore, even if a protein is completely devoid of intrinsically disordered
regions in its mature form (which is a rather exceptional situation), it faces
different forms of disorder (intrinsic, extrinsic, or induced disorder) at all
the stages of its functional life, from birth to death. The goal of this article
is to briefly introduce this concept of disorder in the lifetime of a protein.
PMID- 28516023
TI - Transient disorder: Calcineurin as an example.
AB - How intrinsically disordered proteins and regions evade degradation by cellular
machinery evolved to recognize unfolded and misfolded chains remains a vexing
question. One potential means by which this can occur is the disorder is
transient in nature. That is, the disorder exists just long enough for it to be
bound by a partner biomolecule and fold. A review of 30 y of studies of
calmodulin's activation of calcineurin suggests that the regulatory domain of
this vital phosphatase is a transiently disordered region. During activation, the
regulatory domain progresses from a folded state, to disordered, followed by
folding upon being bound by calmodulin. The transient disordered state of this
domain is part of a critical intermediate state that facilitates the rapid
binding of calmodulin. Building upon "fly-casting" as a means of facilitating
partner binding, the mechanism by which calcineurin undergoes activation and
subsequent deactivation could be considered "catch and release."
PMID- 28516027
TI - Evolutionary journey of the Gc protein (vitamin D-binding protein) across
vertebrates.
AB - With so many diverse functions such as transporter of vitamin D metabolites and
fatty acids, actin scavenger and macrophage activating factor, Gc must have been
one of the most conserved proteins in animal kingdom. Our objective was to
investigate the evolution of Gc by analyzing its differences at protein level.
Using BLAST (Basic Local Alignment Search Tool) searches, Gc amino acid sequences
were analyzed for homology. Clustal W2 and Jalview were used for multiple
sequence alignment analysis, phylogenetic tree by PhyML 3.0 while Batch Web CD
Search Tool was used for identification for conserved domains within protein
sequences. Gc protein percent identity between human and rabbit was 83%, which
decreased to 81% with cow, 78% with mouse, 76% with rat, 51% with chicken, 41%
with frog and 28% with zebrafish. Phylogram showed that rat Gc was the most
diverged, while chicken Gc was the most conserved protein. Analysis also
indicated high homology among mammals (human, rabbit, cow, rat, and mouse). Gc is
a highly conserved protein in chicken and zebrafish. However, the distance from
ancestral protein gradually increased in amphibian (frog) and mammals (human,
rabbit, cow, rat, and mouse). Human Gc and rabbit Gc appear to be recently
evolved proteins. There appears to be an interesting evolutionary pattern-
chicken Gc has the least distance from the ancestral protein, while rat Gc is the
most diverged. There is no vertebrate devoid of Gc which is suggestive of its
important role in vitamin D metabolism in vertebrates.
PMID- 28516026
TI - Strain phenomenon in protein aggregation: Interplay between sequence and
conformation.
AB - Studies of yeast and mammalian prions introduced the idea that the protein
aggregates can exist in multiple stable conformations that can be propagated by
seeding. These conformational states (aka strains) were shown to have distinct
physical (secondary structure, stability) and biological (cytotoxicity,
infectivity) properties. For mammalian prions they were also tied to differences
in disease pathology and incubation time. It was later shown that this phenomenon
is not limited to prion proteins, and distinct conformational states of amyloid
fibrils and oligomers derived from a variety of proteins can be propagated both
in vitro and in vivo. Moreover, in some cases these conformations were preserved
even when propagated into a protein with a different sequence. There is now an
increasing body of evidence that strain phenomenon is a generic feature of
protein aggregation, and characteristic features of amyloid strains can be
transmitted between unrelated sequences.
PMID- 28516025
TI - Designing disorder: Tales of the unexpected tails.
AB - Protein tags of various sizes and shapes catalyze progress in biosciences. Well
folded tags can serve to solubilize proteins. Small, unfolded, peptide-like tags
have become invaluable tools for protein purification as well as protein-protein
interaction studies. Intrinsically Disordered Proteins (IDPs), which lack unique
3D structures, received exponentially increasing attention during the last
decade. Recently, large ID tags have been developed to solubilize proteins and to
engineer the pharmacological properties of protein and peptide pharmaceuticals.
Here, we contrast the complementary benefits and applications of both folded and
ID tags based on predictions of ID. Less structure often means more function in a
shorter tag.
PMID- 28516029
TI - The power of vertical geolocation of atmospheric profiles from GNSS radio
occultation.
AB - High-resolution measurements from Global Navigation Satellite System (GNSS) radio
occultation (RO) provide atmospheric profiles with independent information on
altitude and pressure. This unique property is of crucial advantage when
analyzing atmospheric characteristics that require joint knowledge of altitude
and pressure or other thermodynamic atmospheric variables. Here we introduce and
demonstrate the utility of this independent information from RO and discuss the
computation, uncertainty, and use of RO atmospheric profiles on isohypsic
coordinates-mean sea level altitude and geopotential height-as well as on
thermodynamic coordinates (pressure and potential temperature). Using
geopotential height as vertical grid, we give information on errors of RO-derived
temperature, pressure, and potential temperature profiles and provide an
empirical error model which accounts for seasonal and latitudinal variations. The
observational uncertainty of individual temperature/pressure/potential
temperature profiles is about 0.7 K/0.15%/1.4 K in the tropopause region. It
gradually increases into the stratosphere and decreases toward the lower
troposphere. This decrease is due to the increasing influence of background
information. The total climatological error of mean atmospheric fields is, in
general, dominated by the systematic error component. We use sampling error
corrected climatological fields to demonstrate the power of having different and
accurate vertical coordinates available. As examples we analyze characteristics
of the location of the tropopause for geopotential height, pressure, and
potential temperature coordinates as well as seasonal variations of the
midlatitude jet stream core. This highlights the broad applicability of RO and
the utility of its versatile vertical geolocation for investigating the vertical
structure of the troposphere and stratosphere.
PMID- 28516030
TI - An Algorithm to detect balancing of iterated line sigraph.
AB - A signedgraph (or sigraph in short) S is a graph G in which each edge x carries a
value [Formula: see text] called its sign denoted specially as [Formula: see
text]. Given a sigraph S, H = L(S) called the line sigraph of S is that
sigraph in which edges of S are represented as vertices, two of these vertices
are defined to be adjacent whenever the corresponding edges in S have a vertex in
common and any such edge ef is defined to be negative whenever both e and f are
negative edges in S. Here S is called root sigraph of H. Iterated signed line
graphs [Formula: see text] = [Formula: see text] k [Formula: see text] [Formula:
see text], S:= [Formula: see text] is defined similarly. In this paper, we give
an algorithm to obtain iterated line sigraph and detect for which value of 'k' it
is balanced and determine its complexity. In the end we will propose a technique
that will use adjacency matrix of S and adjacency matrix of [Formula: see text]
which is balanced for some 'k' as a parameter to encrypt a network and forward
the data in the form of balanced [Formula: see text] and will decrypt it by
applying inverse matrix operations.
PMID- 28516031
TI - Identifying appropriate protected areas for endangered fern species under climate
change.
AB - The management of protected areas (PAs) is widely used in the conservation of
endangered plant species under climate change. However, studies that have
identified appropriate PAs for endangered fern species are rare. To address this
gap, we must develop a workflow to plan appropriate PAs for endangered fern
species that will be further impacted by climate change. Here, we used endangered
fern species in China as a case study, and we applied conservation planning
software coupled with endangered fern species distribution data and distribution
modeling to plan conservation areas with high priority protection needs under
climate change. We identified appropriate PAs for endangered fern species under
climate change based on the IUCN protected area categories (from Ia to VI) and
planned additional PAs for endangered fern species. The high priority regions for
protecting the endangered fern species were distributed throughout southern
China. With decreasing temperature seasonality, the priority ranking of all
endangered fern species is projected to increase in existing PAs. Accordingly, we
need to establish conservation areas with low climate vulnerability in existing
PAs and expand the conservation areas for endangered fern species in the high
priority conservation regions.
PMID- 28516032
TI - A case of respiratory infection possibly caused by Mycobacterium triviale:
Current problems on diagnostic and therapeutic strategies.
AB - Mycobacterium triviale is a subspecies of the Mycobacterium terrae complex, which
rarely causes disease in humans. We encountered a case of respiratory infection,
possibly caused by M. triviale, which was successfully treated by levofloxacin
and clarithromycin. Although DNA-DNA hybridization identified M. triviale in one
of three samples, clinical validations convinced us that it was the pathogen. 16s
ribosomal RNA sequencing would have been reliable and ideal to perform in this
case, although it is not covered by the insurance system in Japan. Nevertheless,
this experience remains to be instructive because the clinical course, guidelines
on the diagnosis, and therapeutic strategies for respiratory infections caused by
M. triviale are not well-known or have not been established. Awareness of the
possibility of respiratory infections caused by M. triviale and further
collection and analysis of its predisposing conditions are essential.
PMID- 28516028
TI - Digested disorder: Quarterly intrinsic disorder digest (April-May-June, 2013).
AB - The current literature on intrinsically disordered proteins is overwhelming. To
keep interested readers up to speed with this literature, we continue a "Digested
Disorder" project and represent a series of reader's digest type articles
objectively representing the research papers and reviews on intrinsically
disordered proteins. The only 2 criteria for inclusion in this digest are the
publication date (a paper should be published within the covered time frame) and
topic (a paper should be dedicated to any aspect of protein intrinsic disorder).
The current digest issue covers papers published during the period of April, May,
and June of 2013. The papers are grouped hierarchically by topics they cover, and
for each of the included paper a short description is given on its major
findings.
PMID- 28516034
TI - Synergistic but independent: The role of corticospinal and alternate motor fibers
for residual motor output after stroke.
AB - BACKGROUND: Brain imaging has shown that not only the cortico-spinal tract (CST),
but also alternate corticofugal motor fibers (aMF), such as the cortico-rubro
spinal and cortico-reticulo-spinal tract, influence residual motor output after
stroke. So far, studies mainly have investigated each tract separately. A
combined analysis of CST and aMF with assessment of their interactive role, i.e.,
that structural integrity of one tract influences the functional role of the
structural integrity of the other, is pending. METHODS: 39 late subacute stroke
patients (aged 59.4 +/- 12.0 years, 100 +/- 11 days after stroke) were included.
Probabilistic tractography was used to reconstruct CST and aMF. Fractional
anisotropy (FA) was calculated as a measure of microstructural integrity.
Multiple-linear-regression analysis was used to associate tract-related FA with
residual motor output and to determine interactions between CST and aMF. RESULTS:
Both CST (coefficient = 3.93, p < 0.0001) and aMF (coefficient = - 4.43, p =
0.003) of the affected hemisphere significantly contributed to residual motor
output. An interaction of their impacts with a consecutive influence on motor
output was not detected (p = 0.882). Thus, these data suggest that aMF and CST
explain residual motor output in stroke patients in a synergistic, but mainly
independent manner. CONCLUSIONS: The structural states of the CST and also - to a
smaller degree - of the aMF correlate with residual motor output in late subacute
stroke patients. Based on this statistical modeling with all inherent
limitations, the novel finding of an absence of a significant interaction between
both tracts in regard of their functional role, suggests that both corticofugal
pathways act synergistically but largely independently. These findings add to the
understanding of the functional role of different corticofugal motor fibers and
their interactions for motor output after stroke.
PMID- 28516035
TI - DNA shotgun sequencing analysis of Garcinia mangostana L. variety Mesta.
AB - Mangosteen (Garcinia mangostana Linn.) is an ultra-tropical tree characterized by
its unique dark purple fruits with white flesh. The xanthone-rich purple pericarp
tissue contains valuable compounds with medicinal properties. Following
previously reported genome sequencing of a common variety of mangosteen [1], we
performed another whole genome sequencing of a commercially popular variety of
this fruit species (var. Mesta) for comparative analysis of its genome
composition. Raw reads of the DNA sequencing project were deposited to SRA
database with the accession number SRX2709728.
PMID- 28516036
TI - Transcriptome analysis of Carica papaya embryogenic callus upon De-etiolated 1
(DET1) gene suppression.
AB - Papaya is considered to be one of the most nutritional fruits. It is rich in
vitamins, carotenoids, flavonoids and other phytonutrient which function as
antioxidant in our body [1]. Previous studies revealed that the suppression of a
negative regulator gene in photomorphogenesis, De-etiolated 1 (DET1) can improve
the phytonutrient in tomato and canola without affecting the fruit quality [2],
[3]. This report contains the experimental data on high-throughput 3' mRNA
sequencing of transformed papaya callus upon DET1 gene suppression.
PMID- 28516037
TI - Zika virus infection in a newly married Greek couple.
AB - Zika virus (ZIKV) is a member of the Flaviviridae family causing asymptomatic or
mildly symptomatic infections with fever, rash, arthralgia and headache. It is
transmitted by the Aedes species mosquitoes and also sexually and
transplacentally, and has been recently associated with congenital neurologic
birth defects in South and Central America. We report the case of a newly married
couple from Greece who travelled to Cuba for their honeymoon and developed mild
symptoms consistent with arboviral infection. After returning to Greece, they
were found to have been infected by Zika virus during their honeymoon. These are
the first two cases of Zika virus infection in Greece, the southeastern border of
Europe, denoting that Zika virus infection poses a threat for public health
worldwide, since returning travelers could be asymptomatic carriers of the virus,
not only leading to risk of neurologic birth defects for their offspring but also
the real risk of transmission of the virus in their country by local Aedes
mosquitoes.
PMID- 28516033
TI - The impact of large structural brain changes in chronic stroke patients on the
electric field caused by transcranial brain stimulation.
AB - Transcranial magnetic stimulation (TMS) and transcranial direct current
stimulation (TDCS) are two types of non-invasive transcranial brain stimulation
(TBS). They are useful tools for stroke research and may be potential adjunct
therapies for functional recovery. However, stroke often causes large cerebral
lesions, which are commonly accompanied by a secondary enlargement of the
ventricles and atrophy. These structural alterations substantially change the
conductivity distribution inside the head, which may have potentially important
consequences for both brain stimulation methods. We therefore aimed to
characterize the impact of these changes on the spatial distribution of the
electric field generated by both TBS methods. In addition to confirming the
safety of TBS in the presence of large stroke-related structural changes, our aim
was to clarify whether targeted stimulation is still possible. Realistic head
models containing large cortical and subcortical stroke lesions in the right
parietal cortex were created using MR images of two patients. For TMS, the
electric field of a double coil was simulated using the finite-element method.
Systematic variations of the coil position relative to the lesion were tested.
For TDCS, the finite-element method was used to simulate a standard approach with
two electrode pads, and the position of one electrode was systematically varied.
For both TMS and TDCS, the lesion caused electric field "hot spots" in the
cortex. However, these maxima were not substantially stronger than those seen in
a healthy control. The electric field pattern induced by TMS was not
substantially changed by the lesions. However, the average field strength
generated by TDCS was substantially decreased. This effect occurred for both head
models and even when both electrodes were distant to the lesion, caused by
increased current shunting through the lesion and enlarged ventricles. Judging
from the similar peak field strengths compared to the healthy control, both TBS
methods are safe in patients with large brain lesions (in practice, however,
additional factors such as potentially lowered thresholds for seizure-induction
have to be considered). Focused stimulation by TMS seems to be possible, but
standard tDCS protocols appear to be less efficient than they are in healthy
subjects, strongly suggesting that tDCS studies in this population might benefit
from individualized treatment planning based on realistic field calculations.
PMID- 28516039
TI - A plane screw fixation is a nidus for Paecilomyces sinusitis in a patient with
aspirin exacerbated respiratory disease.
AB - Titanium plane screw fixation of the frontal sinus is an approach used by
otolaryngologists to obliterate this space in an attempt to reduce sinus
infections. In this case, however, the titanium used became a nidus of infection
which cultured the fungus Paecilomyces. The patient also had a hypersensitivity
reaction to mold with positive skin tests and IgE, as well as eosinophilic
esophagitis. Treatment entailed anti-fungals, anti-IgE, and fungal immunotherapy
to multiple fungal antigens prevalent to the geographic region. The patient also
had aspirin exacerbated respiratory disease which responded to aspirin
desensitization. Her symptoms resolved after 3 months.
PMID- 28516040
TI - A newborn case with carnitine palmitoyltransferase II deficiency initially judged
as unaffected by acylcarnitine analysis soon after birth.
AB - Carnitine palmitoyltransferase II (CPT-2) deficiency, an autosomal recessive
disorder of fatty acid oxidation, can be detected by newborn screening using
tandem mass spectrometry (TMS). Our case was a boy born at 38 weeks and 6 days of
gestation via normal vaginal delivery; his elder sister was affected with CPT-2
deficiency. Acylcarnitine (AC) was analyzed in both dried blood spots (DBS) and
serum 2 h after birth to determine whether the boy was also affected. His C16 and
C18:1 AC levels in DBS were in the normal range, while his serum long-chain AC
levels were marginally increased but lower than those of his sister. After the
samples were taken, he was treated with glucose infusion to prevent any
catabolism for 2 days. On day 4, the long-chain AC levels in both DBS and serum
obtained were higher than those on day 0 and were equivalent to those of his
sister. Genetic testing confirmed the presence of the same mutation found in his
sister, a homozygous F383Y mutation in the CPT2 gene, thus leading to the
diagnosis of CPT-2 deficiency. The sample for TMS should be taken between days 1
and 7. If the sample is not obtained at an appropriate time, correct diagnosis
may not be made, as in our case. Although early diagnosis is required, samples
taken within 24 h after birth should not be used for TMS.
PMID- 28516038
TI - Detection of Fusobacterium nucleatum in culture-negative brain abscess by broad
spectrum bacterial 16S rRNA Gene PCR.
AB - BACKGROUND: Fusobacterium nucleatum is a strict anaerobic microorganism commensal
to the human oropharynx and gastrointestinal tract, which causes a wide spectrum
of human diseases and it is an important pathogen in abscesses. CASE
PRESENTATION: We report the case of a previously healthy 64-year-old woman with
multiple abscesses due to Fusobacterium nucleatum, involving liver, pleura and
brain. Fusobacterium was not recovered from blood cultures nor from culture of
hepatic, pleural and brain drain fluid. The diagnosis was obtained by polymerase
chain reaction amplification of bacterial deoxyribonucleic acid in brain abscess
drain. CONCLUSIONS: Fusobacterium spp., should be considered in patients with any
organ abscess, especially in case of invasive disease with multiple secondary
site involving brain. MOLECULAR: techniques might be of special usefulness in
cases that remain negative in culture to obtain the diagnosis and perform
adequate treatment.
PMID- 28516041
TI - Birth weight in patients with mucopolysaccharidosis type II: Data from the Hunter
Outcome Survey (HOS).
AB - There is a need to identify early disease markers to facilitate diagnosis of
mucopolysaccharidosis type II (MPS II; Hunter syndrome). Mean birth weight and
its association with disease severity was investigated in 609 patients enrolled
in the Hunter Outcome Survey (HOS). This analysis indicated that birth weight is
not an early marker of MPS II and is not associated with disease severity. It
remains important to investigate the utility of other factors for early/pre
symptomatic diagnosis.
PMID- 28516042
TI - Sensitivity enhancement of traveling wave MRI using free local resonators: an
experimental demonstration.
AB - BACKGROUND: Traveling wave MR uses the far fields in signal excitation and
reception, therefore its acquisition efficiency is low in contrast to the
conventional near field magnetic resonance (MR). Here we show a simple and
efficient method based on the local resonator to improving sensitivity of
traveling wave MR technique. The proposed method utilizes a standalone or free
local resonator to amplify the radio frequency magnetic fields in the interested
target. The resonators have no wire connections to the MR system and thus can be
conveniently placed to any place around imaging simples. METHODS: A rectangular
loop L/C resonator to be used as the free local resonator was tuned to the proton
Larmor frequency at 7T. Traveling wave MR experiments with and without the
wireless free local resonator were performed on a living rat using a 7T whole
body MR scanner. The signal-to-noise ratio (SNR) or sensitivity of the images
acquired was compared and evaluated. RESULTS: In vivo 7T imaging results show
that traveling wave MR with a wireless free local resonator placed near the head
of a living rat achieves at least 10-fold SNR gain over the images acquired on
the same rat using conventional traveling wave MR method, i.e. imaging with no
free local resonators. CONCLUSIONS: The proposed free local resonator technique
is able to enhance the MR sensitivity and acquisition efficiency of traveling
wave MR at ultrahigh fields in vivo. This method can be a simple solution to
alleviating low sensitivity problem of traveling wave MRI.
PMID- 28516043
TI - Quantification of regional deformation of the lungs by non-rigid registration of
three-dimensional contrast-enhanced magnetic resonance imaging.
AB - BACKGROUND: Assessment of lung function is vital for the diagnosis of a variety
of pathological conditions. Research has been proposed to study pulmonary
mechanics and kinematics using two-dimensional (2D) magnetic resonance imaging
(MRI). This allows estimation of regional lung tissue mechanics but is limited to
2D information. An approach based on three-dimensional (3D) contrast-enhanced MR
angiogram of pulmonary blood vessels and a non-rigid image registration technique
is proposed for quantification of lung regional deformations, which can
potentially be used for assessment of pulmonary parenchymal mechanics and
regional ventilation for disease diagnosis without ionizing radiation. METHODS:
On three volunteers, an end-expiration scan and end-inspiration scan was acquired
successively for each volunteer using a 3D breath-hold contrast-enhanced MRI
sequence several minutes after gadolinium injection. Subsequently, a rectangle
box lung mask is manually selected for each end-expiration scan, applying non
rigid registration algorithms using cubic B-splines as transformations to align
each pair of images. This incorporates the Normalized Correlation Coefficient
similarity with the bending energy term as cost function with a multi-resolution
multi-grid approach. Finally, the lung regional 3D deformations were obtained
using the transformations obtained by registration. The alignment accuracy after
non-rigid registration was estimated by using a set of branch points of pulmonary
blood vessels as anatomical landmarks for each pair of images. RESULTS: With
contrast enhancement, the pulmonary blood vessel signal was enhanced, which
greatly facilitated the non-rigid registration in the lung parenchyma. The
average landmarks distances in three pairs of datasets are reduced from 17.9,
20.3 and 16.3 mm, to 1.0, 1.6 and 1.2 mm, respectively, by non-rigid
registration. After registration, the average distances error of each pair of
datasets was less than 0.6 mm in the right-to-left (RL) direction, less than 0.9
mm in the inferior-to-superior (IS) direction, and less than 1.2 mm in the
anterior-to-posterior (AP) direction. CONCLUSIONS: Results demonstrated that the
proposed method can accurately register lungs with large deformations to evaluate
lung regional deformation. It may be used for quantitative assessment of 3D lung
regional ventilation avoiding ionizing radiation.
PMID- 28516044
TI - Design of catheter radio frequency coils using coaxial transmission line
resonators for interventional neurovascular MR imaging.
AB - BACKGROUND: It is technically challenging to design compact yet sensitive
miniature catheter radio frequency (RF) coils for endovascular interventional MR
imaging. METHODS: In this work, a new design method for catheter RF coils is
proposed based on the coaxial transmission line resonator (TLR) technique. Due to
its distributed circuit, the TLR catheter coil does not need any lumped
capacitors to support its resonance, which simplifies the practical design and
construction and provides a straightforward technique for designing miniature
catheter-mounted imaging coils that are appropriate for interventional
neurovascular procedures. The outer conductor of the TLR serves as an RF shield,
which prevents electromagnetic energy loss, and improves coil Q factors. It also
minimizes interaction with surrounding tissues and signal losses along the
catheter coil. To investigate the technique, a prototype catheter coil was built
using the proposed coaxial TLR technique and evaluated with standard RF testing
and measurement methods and MR imaging experiments. Numerical simulation was
carried out to assess the RF electromagnetic field behavior of the proposed TLR
catheter coil and the conventional lumped-element catheter coil. RESULTS: The
proposed TLR catheter coil was successfully tuned to 64 MHz for proton imaging at
1.5 T. B1 fields were numerically calculated, showing improved magnetic field
intensity of the TLR catheter coil over the conventional lumped-element catheter
coil. MR images were acquired from a dedicated vascular phantom using the TLR
catheter coil and also the system body coil. The TLR catheter coil is able to
provide a significant signal-to-noise ratio (SNR) increase (a factor of 200 to
300) over its imaging volume relative to the body coil. CONCLUSIONS: Catheter
imaging RF coil design using the proposed coaxial TLR technique is feasible and
advantageous in endovascular interventional MR imaging applications.
PMID- 28516045
TI - Exploration of highly accelerated magnetic resonance elastography using high
density array coils.
AB - BACKGROUND: Magnetic resonance elastography (MRE) measures tissue mechanical
properties by applying a shear wave and capturing its propagation using magnetic
resonance imaging (MRI). By using high density array coils, MRE images are
acquired using single echo acquisition (SEA) and at high resolutions with
significantly reduced scan times. METHODS: Sixty-four channel uniplanar and 32*32
channel biplanar receive arrays are used to acquire MRE wave image sets from agar
samples containing regions of varying stiffness. A mechanical actuator triggered
by a stepped delay time introduces vibrations into the sample while a motion
sensitizing gradient encodes micrometer displacements into the phase. SEA imaging
is used to acquire each temporal offset in a single echo, while multiple echoes
from the same array are employed for highly accelerated imaging at high
resolutions. Additionally, stiffness variations as a function of temperature are
studied by using a localized heat source above the sample. A custom insertable
gradient coil is employed for phase compensation of SEA imaging with the biplanar
array to allow imaging of multiple slices. RESULTS: SEA MRE images show a
mechanical shear wave propagating into and across agar samples. A set of 720
images was obtained in 720 echoes, plus a single reference scan for both harmonic
and transient MRE. A set of 2,950 wave image frames was acquired from pairs of
SEA images captured during heating, showing the change in mechanical wavelength
with the change in agar properties. A set of 240 frames was acquired from two
slices simultaneously using the biplanar array, with phase images processed into
displacement maps. Combining the narrow sensitivity patterns and SNR advantage of
the SEA array coil geometry allowed acquisition of a data set with a resolution
of 156 um * 125 um * 1,000 um in only 64 echoes, demonstrating high resolution
and high acceleration factors. CONCLUSIONS: MRE using high-density arrays offers
the unique ability to acquire a single frame of a propagating mechanical
vibration with each echo, which may be helpful in non-repeatable or destructive
testing. Highly accelerated, high resolution MRE may be enabled by the use of
large arrays of coils such as used for SEA, but at lower acceleration rates
supporting the higher resolution than provided by SEA imaging.
PMID- 28516046
TI - Image quality assessment of a 1.5T dedicated magnetic resonance-simulator for
radiotherapy with a flexible radio frequency coil setting using the standard
American College of Radiology magnetic resonance imaging phantom test.
AB - BACKGROUND: A flexible RF coil setting has to be used on an MR-simulator (MR-sim)
in the head and neck simulation scan for radiotherapy (RT) purpose, while the
image quality might be compromised due to the sub-optimized flexible coil
compared to the normal diagnostic radiological (DR) head coil. In this study, we
assessed the image quality of an MR-sim by conducting the standard American
College of Radiology (ACR) MRI phantom test on a 1.5T MR-sim under RT-setting and
comparing it to DR-setting. METHODS: A large ACR MRI phantom was carefully
positioned, aligned and scanned 9 times for each under RT- and DR-setting on a
1.5T MR-sim, following the ACR scanning instruction. Images were analyzed
following the ACR guidance. Measurement results under two coil settings were
quantitatively compared. Inter-observer disagreements under RT-setting between
two physicists were compared using Bland-Altman (BA) analysis and intra-class
correlation coefficient (ICC). RESULTS: The MR-sim with RT-setting obtained
sufficiently good image quality to pass all ACR recommended criteria. No
significant difference was found in phantom length accuracy, high-contrast
spatial resolution, slice thickness accuracy, slice position accuracy, and
percent-signal ghosting. RT-setting significantly under-performed in low-contrast
object detectability, while better performed in image intensity uniformity. BA
analysis showed that 95% limit of agreement and biases of phantom test
measurement under RT-setting between two observers were very small. Excellent
inter-observer agreement (ICC >0.75) was achieved in all measurements except for
slice thickness accuracy (ICC =0.42, moderate agreement) under RT-setting.
CONCLUSIONS: Very good and highly reproducible image quality could be achieved on
a 1.5T MR-sim with a flexible coil setting as revealed by the standard ACR MRI
phantom test. The flexible RT-setting compromised in image signal-to-noise ratio
(SNR) compared to the normal DR-setting, and resulted in reduced low-contrast
object detectability.
PMID- 28516047
TI - Prospective cardiac motion self-gating.
AB - BACKGROUND: To develop a prospective cardiac motion self-gating method that
provides robust and accurate cardiac triggers in real time. METHODS: The proposed
self-gating method consists of an "imaging mode" that acquires the k-space
segments and a "self-gating mode" that captures the cardiac motion by repeatedly
sampling the k-space centerline. A training based principal component analysis
algorithm is utilized to process the self-gating data where the projection onto
the first principal component was used as the self-gating signal. Retrospective
studies using a sequence with self-gating mode only was performed on 8 healthy
subjects to validate the accuracy and reliability of the self-gating triggers.
Prospective studies using both ECG-gated and self-gated cardiac CINE sequences
were conducted on 6 healthy subjects to compare the image quality. RESULTS: Using
the ECG as the reference, the proposed method was able to detect self-gating
triggers within +/-10 ms accuracy on all 8 subjects in the retrospective study.
The prospectively self-gated CINE sequence successfully detected 100% of the
cardiac triggers and provided excellent CINE image quality without using ECG
signals. CONCLUSIONS: The proposed cardiac self-gating method is a robust and
accurate alternative to conventional ECG-based gating method for a number of
cardiac MRI applications.
PMID- 28516049
TI - Analysis of phase error effects in multishot diffusion-prepared turbo spin echo
imaging.
AB - BACKGROUND: To characterize the effect of phase errors on the magnitude and the
phase of the diffusion-weighted (DW) signal acquired with diffusion-prepared
turbo spin echo (dprep-TSE) sequences. METHODS: Motion and eddy currents were
identified as the main sources of phase errors. An analytical expression for the
effect of phase errors on the acquired signal was derived and verified using
Bloch simulations, phantom, and in vivo experiments. RESULTS: Simulations and
experiments showed that phase errors during the diffusion preparation cause both
magnitude and phase modulation on the acquired data. When motion-induced phase
error (MiPe) is accounted for (e.g., with motion-compensated diffusion encoding),
the signal magnitude modulation due to the leftover eddy-current-induced phase
error cannot be eliminated by the conventional phase cycling and sum-of-squares
(SOS) method. By employing magnitude stabilizers, the phase-error-induced
magnitude modulation, regardless of its cause, was removed but the phase
modulation remained. The in vivo comparison between pulsed gradient and flow
compensated diffusion preparations showed that MiPe needed to be addressed in
multi-shot dprep-TSE acquisitions employing magnitude stabilizers. CONCLUSIONS: A
comprehensive analysis of phase errors in dprep-TSE sequences showed that
magnitude stabilizers are mandatory in removing the phase error induced magnitude
modulation. Additionally, when multi-shot dprep-TSE is employed the inconsistent
signal phase modulation across shots has to be resolved before shot-combination
is performed.
PMID- 28516048
TI - Image interpolation improves the zonal analysis of cartilage T2 relaxation in
MRI.
AB - BACKGROUND: This project aimed to investigate the improvement in the detection of
osteoarthritis (OA) in cartilage by the interpolation of T2 images, in the
situation when the native MRI resolution is insufficient to resolve the depth
dependent T2 characteristics in articular cartilage (AC). METHODS: Eighteen
intact canine knee joints that were healthy or had mild (contralateral) or severe
OA were T2-imaged in a 7T/20 cm MRI system at 200 um/pixel resolution (macro
MRI). Two image analysis methods were used to interpolate the images to 100
um/pixel, i.e., by Fourier-transforming the time-domain FID (Free Induction
Decay) signal using the Varian NMR software and by interpolating the 2D T2 image
using the ImageJ software. RESULTS: The T2 profiles from 30 individual ROI of
each healthy [6], mild [6] and OA [6] cartilage at 200 um and the interpolated
100 um resolutions were subdivided into two equal-thickness regions and three
equal thickness regions based on clinical MRI protocols. A new method divided the
T2 profiles into three-unequal thickness zones according to the T2 profiles at
17.6 um/pixel from the same cartilage imaged in a 7 Tesla/9 cm uMRI system. Both
interpolation methods improved the depth-dependent T2 images/profiles in macro
MRI. The unequal zone division in T2 had better OA sensitivity than the equal
zone division. The three-equal zone division of T2 profiles had better OA
sensitivity than the two-equal zone division. The statistical significant
difference between the healthy and mild OA cartilage is detected (P=0.0018) only
by the unequal zone division method at 100 um resolution. CONCLUSIONS: Data
interpolation improves the T2 sensitivity in MRI of cartilage OA. Unequal
division of tissue thickness enables better early stage of OA detection than the
equal division.
PMID- 28516050
TI - Towards MRI temperature mapping in real time-the proton resonance frequency
method with undersampled radial MRI and nonlinear inverse reconstruction.
AB - BACKGROUND: Optimal control of minimally invasive interventions by hyperthermia
requires dynamic temperature mapping at high temporal resolution. METHODS: Based
on the temperature-dependent shift of the proton resonance frequency (PRF), this
work developed a method for real-time MRI thermometry which relies on highly
undersampled radial FLASH MRI sequences with iterative image reconstruction by
regularized nonlinear inversion (NLINV). As a first step, the method was
validated with use of a temperature phantom and ex vivo organs (swine kidney)
subjected to heating by warm water or a pulsed laser source. RESULTS: The
temperature maps obtained by real-time PRF MRI demonstrate good accuracy as
independently controlled by fiber-optic temperature sensors. Moreover, the
dynamic results demonstrate both excellent sensitivity to single laser pulses (20
ms duration, 6 J energy output) and high temporal resolution, i.e., 200 ms
acquisition times per temperature map corresponding to a rate of 5 frames per
second. In addition, future extensions to in vivo applications were prepared by
addressing the breathing-related motion problem by a pre-recorded library of
reference images representative of all respiratory states. CONCLUSIONS: The
proposed method for real-time MRI thermometry now warrants further developments
towards in vivo MRI monitoring of thermal interventions in animals.
PMID- 28516051
TI - Evaluation of MR thermometry with proton resonance frequency method at 7T.
AB - Quantitative and non-invasive temperature mapping using magnetic resonance
imaging (MRI) provides a unique way to measure temperature evolution inside
biological tissues. The method is widely used in thermal ablation procedures with
magnetic fields at or below 3T. In this paper, the sensitivity of the MRI
thermometry at 7T was studied using a proton resonance frequency (PRF)-based
technique. We first used an agarose gel phantom with MR-compatible thermometry to
calibrate the temperature coefficient, and then this temperature coefficient was
employed to measure the internal temperature in both ex vivo (beef muscle) and in
vivo (rat) experiments using focused ultrasound heating. The temperature
coefficient calibrated by the phantom was 0.0095 ppm/ degrees C, and both the ex
vivo and in vivo experiments exhibited clear temperature evolution. This
quantitative study confirmed the sensitivity (<1 degrees C) of MR temperature
mapping at 7T.
PMID- 28516053
TI - Implication of pulmonary-systemic flow information in the management of complex
presentation of pulmonary arterial hypertension: exploring role of phase contrast
MRI technique.
PMID- 28516054
TI - Current trends in bone tissue regeneration.
PMID- 28516052
TI - Whole body MRI of the non-human primate using a clinical 3T scanner: initial
experiences.
AB - With the advent of parallel imaging MRI techniques, whole-body MRI is being
increasingly used in clinical diagnosis. However, its application in preclinical
research using large animals remains very limited. In the present study, the
whole-body MRI techniques for adult macaque monkeys were explored using a
conventional clinic 3T scanner. The T1, T2 anatomical images, and MR angiography
of adult macaque whole bodies were illustrated. The preliminary results suggest
whole-body MRI can be a robust tool to examine multiple organs of non-human
primate (NHP) models from head to toe non-invasively and simultaneously using a
conventional clinical setting. As NHPs are intensely used in biomedical research
such as HIV/AIDS and vaccine discovery, whole body MRI techniques can have a wide
range of applications in translational research using NHPs.
PMID- 28516055
TI - Antimicrobial and enzymatic activity of actinomycetes isolated from soils of
coastal islands.
AB - Microbiological investigation of unexplored ecosystems is crucial for discovering
of antibiotic producing actinomycetes. The present study was conducted to
determine antimicrobial activity and identify the most active strains.
Actinomycetes were isolated using the spread plate technique following by serial
dilution of samples on starch casein agar. The screening method consists of
primary and secondary testing. The most active isolates were identified based on
molecular and cultural methods. 42 out of 66 isolates displayed antimicrobial
potential. 63% exhibited antibacterial activity, 16% antifungal activity, and 16%
displayed both activities. Identified isolates, Streptomyces scabrisporus,
Streptomyces sparsogenes, Streptomyces misakiensis, Streptomyces cirratus,
Streptomyces lincolnensis, Streptomyces endophyticus, Streptomyces chartreusis,
and Streptomyces alboniger showed a broad spectrum of enzymatic activities. The
results indicated that these isolates may serve as antibiotic and enzyme
producing microbes.
PMID- 28516056
TI - Simultaneous micronization and purification of bioactive fraction by
supercritical antisolvent technology.
AB - Simultaneous micronization and purification of DLBS3233 bioactive fraction, a
combination of two Indonesian herbals Lagerstroemia speciosa and Cinnamomum
burmannii has been successfully performed via supercritical anti-solvent (SAS)
technology. The objective of the present study was to investigate the
effectiveness of SAS technology to micronize and reduce coumarin content of
DLBS3233. The effects of four SAS process parameters, i.e. pressure, temperature,
concentration and solution flow rate on particle formation were investigated. In
SAS process, DLBS3233 was dissolved in dimethylformamide (DMF) as the liquid
solvent. The solution was then pumped through a nozzle into a chamber
simultaneously with supercritical carbon dioxide (SC-CO2) which acts as the anti
solvent, resulting in DLBS3233 precipitation. Physicochemical properties of
unprocessed DLBS3233 and SAS-processed DLBS3233 particles were analyzed using
scanning electron microscopy (SEM) and high pressure liquid chromatography
(HPLC). Total polyphenol content (TPC) was also analyzed. Particles with mean
particle size ranging from 0.107+/-0.028 MUm to 0.298+/-0.138 MUm were obtained
by varying the process parameters. SAS-processed DLBS3233 particles showed no
coumarin content in all experiments studied in this work. Results of TPC analysis
revealed no significant change in SAS-processed DLBS3233 particles compared to
unprocessed DLBS3233. Nano-sized DLBS3233 particles with no coumarin content have
been successfully produced using SAS process. This study demonstrates the ability
of SAS for processing herbal medicine in single step process.
PMID- 28516057
TI - Comparison of atracurium and methocarbamol for preventing succinylcholine-induced
muscle fasciculation: A randomized controlled trial.
AB - Fasciculation is a minor adverse effect of succinylcholine and may be an
unpleasant experience for patient. The aim of this study was to compare the use
of atracurium and methocarbamol to decrease the occurrence and severity of
succinylcholine-induced muscle fasciculation. Fifty-nine adults with American
Society of Anesthesiologists I or II hospitalized for elective surgery were
randomly assigned to two groups: Group A (n = 29) who received succinylcholine 1
mg/kg body weight (BW) intravenously followed by 0.2-0.5 mg/kg BW atracurium and
patients in Group B (n= 29) who received succinylcholine 1 mg/kg BW intravenously
followed by methocarbamol 0.2-0.5 mg/kg BW. Anesthesia was induced in all
patients with thiopental sodium 3-5 mg/kg. Fasciculation was scored on a four
point (0-4) Likert scale. There were no statistically significant differences in
demographic variables between two groups, whereas in Group A, 27 patients (93.1%)
suffered from mild fasciculation and two (6.9%) from moderate fasciculation. In
Group B, twenty patients (68.9%) suffered from mild fasciculation, five (17.2%)
from moderate fasciculation, and four (13.9%) from severe fasciculation. The
difference between the groups was statistically significant (P < 0.05).
Atracurium is more effective than methocarbamol in decreasing the occurrence and
severity of succinylcholine-induced fasciculations. In addition, the use of
methocarbamol before succinylcholine administration can decrease the incidence of
severe fasciculation.
PMID- 28516058
TI - Comparison of amoxicillin and metronidazole effect on three-drug regimen for the
treatment of Helicobacter pylori infection in children.
AB - Helicobacter pylori is an important risk factor for chronic gastritis, peptic
ulcer, and gastric cancer. Three-drug regimen is the first-line treatment for
this infection, but the response rate to treatment varies in different
geographical regions. This study was conducted to comparatively determine the
effect of amoxicillin and metronidazole on three-drug regimen to treat H. pylori
infection in 1-15-year-old children. This clinical trial was conducted on 82
patients aged 1-15 years with convenience sampling referring to the Endoscopy
Unit of Hajar Hospital, Shahrekord. Group 1 was administered with clarithromycin,
amoxicillin, and omeprazole (CAO), and Group 2 with, clarithromycin,
metronidazole, and omeprazole (CMO). One month after completion of the treatment,
stool antigen test was used to study the eradication of H. pylori. Data were
analyzed using SPSS software by Chi-square test. Three of the 82 patients were
excluded from the study because of side effects caused by drugs. Nearly 87.2% of
the patients in CAO-treated group and 92.5% in CMO-treated group had response to
treatment. There was no significant difference in eradication rate between the
two regimens (P = 0.43). The two regimens displayed no superiority over each
other for eradicating H. pylori infection and response rate to treatment in
children aged 1-15 years.
PMID- 28516059
TI - The effects of cognitive behavioral therapy and drug therapy on quality of life
and symptoms of patients with irritable bowel syndrome.
AB - Psychotherapy and drug therapy are considered useful in quality of life (QOL) and
symptoms of patients with irritable bowel syndrome (IBS). The aim of this study
was to examine the effects of cognitive behavioral therapy (CBT) associated with
drug therapy in comparison to drug therapy alone on the QOL and symptoms of IBS
patients with diarrhea predominance. This study was a randomized clinical trial
on 64 IBS patients. The patients were selected according to Rome III criteria and
were assigned into two groups. Bowel symptom severity and frequency scale and QOL
IBS were used to investigate the patients' symptoms. The first group underwent
CBT with medication therapy, and the second group received only medication. Data
were analyzed using analysis of multiple covariance. The two groups showed a
significant difference in the QOL-IBS in posttreatment and follow-up stages (P <
0.05). There were significant differences in the severity and frequency of IBS
symptoms between the two groups after the intervention (P < 0.05). However, no
significant difference was observed at follow-up stage between the two groups (P
> 0.05). CBT accompanied by drug therapy can be useful for IBS patients with
diarrhea predominance. However, discontinuing this treatment may lead to
recurrence of the symptoms.
PMID- 28516061
TI - The effect of vaginal cream containing ginger in users of clotrimazole vaginal
cream on vaginal candidiasis.
AB - Vulvovaginal candidiasis is one of the most common infections of the genital
tract in women that causes many complications. Therefore, we examined the
clinical effect of ginger cream along with clotrimazole compared to vaginal
clotrimazole alone in this study. This double-blind clinical trial was conducted
on 67 women admitted to the Gynecology Clinic of Hajar Hospital with vaginal
candidiasis. The patients were divided randomly into two groups of 33 and 34
people. The diagnosis was made according to clinical symptoms, wet smear, and
culture. Ginger-clotrimazole vaginal cream 1% and clotrimazole vaginal cream 1%
were administered to groups 1 and 2, respectively, once a day for 7 days and
therapeutic effects and symptoms were evaluated in readmission. Data analysis was
performed using SPSS version 22, t-test and Chi-square. The mean value of
variables itching (P > 0.05), burning (P > 0.05), and cheesy secretion (P < 0.05)
in users of ginger-clotrimazole was less than the other group after the
treatment. Recurrence in clotrimazole group was 48.5% and in ginger-clotrimazole
group 51.2% during the 1-month follow-up with no significant difference. Study
results showed that cream containing ginger and clotrimazole 1% was more
effective and may be more useful than the clotrimazole to treat vaginal
candidiasis.
PMID- 28516060
TI - The effects of Vitamin C on sperm quality parameters in laboratory rats following
long-term exposure to cyclophosphamide.
AB - Cyclophosphamide is a widely used medication and can cause oxidative stress. This
study was conducted to investigate the effects of Vitamin C on reproductive
organs' weight and the quality of sperm parameters in laboratory rats. In this
experimental study, 40 rats were randomly assigned into five groups of eight
each. Distilled water (DW) group received only food and water, Group 2 was
administered with drug solvent (DW) by gavage, Group 3 intraperitoneally
administered with 1.6 mg/kg cyclophosphamide, Group 4 gavaged Vitamin C at 0.88
mg/kg, and Group 5 administered with effective doses of Vitamin C and
cyclophosphamide by gavage with 1-h intervals. Sperm parameters of the samples
were taken from distal epididymis and tissues were studied, and the data were
analyzed by SPSS version 22. The lowest weight of testicles and epididymis was
seen in cyclophosphamide-exposed rats and the highest weight of testicles and
epididymis in Vitamin C-exposed rats (P < 0.05). The highest motility,
progression, viability, and count of sperm were seen in the Vitamin C-treated
group and the lowest in the cyclophosphamide-exposed group. The highest
proportion of sperm anomalies was seen in the cyclophosphamide-exposed group.
Vitamin C, as an antioxidant, can be effective on some of the sperm parameters
and can reduce cyclophosphamide-induced complications in animal model.
PMID- 28516062
TI - Endoplasmic Reticulum-Mitochondrial Ca2+ Fluxes Underlying Cancer Cell Survival.
AB - Calcium ions (Ca2+) are crucial, ubiquitous, intracellular second messengers
required for functional mitochondrial metabolism during uncontrolled
proliferation of cancer cells. The mitochondria and the endoplasmic reticulum
(ER) are connected via "mitochondria-associated ER membranes" (MAMs) where ER
mitochondria Ca2+ transfer occurs, impacting the mitochondrial biology related to
several aspects of cellular survival, autophagy, metabolism, cell death
sensitivity, and metastasis, all cancer hallmarks. Cancer cells appear addicted
to these constitutive ER-mitochondrial Ca2+ fluxes for their survival, since they
drive the tricarboxylic acid cycle and the production of mitochondrial substrates
needed for nucleoside synthesis and proper cell cycle progression. In addition to
this, the mitochondrial Ca2+ uniporter and mitochondrial Ca2+ have been linked to
hypoxia-inducible factor 1alpha signaling, enabling metastasis and invasion
processes, but they can also contribute to cellular senescence induced by
oncogenes and replication. Finally, proper ER-mitochondrial Ca2+ transfer seems
to be a key event in the cell death response of cancer cells exposed to
chemotherapeutics. In this review, we discuss the emerging role of ER
mitochondrial Ca2+ fluxes underlying these cancer-related features.
PMID- 28516063
TI - Modulation of Ca2+ Signaling by Anti-apoptotic B-Cell Lymphoma 2 Proteins at the
Endoplasmic Reticulum-Mitochondrial Interface.
AB - Mitochondria are important regulators of cell death and cell survival.
Mitochondrial Ca2+ levels are critically involved in both of these processes. On
the one hand, excessive mitochondrial Ca2+ leads to Ca2+-induced mitochondrial
outer membrane permeabilization and thus apoptosis. On the other hand,
mitochondria need Ca2+ in order to efficiently fuel the tricarboxylic acid cycle
and maintain adequate mitochondrial bioenergetics. For obtaining this Ca2+, the
mitochondria are largely dependent on close contact sites with the endoplasmic
reticulum (ER), the so-called mitochondria-associated ER membranes. There, the
inositol 1,4,5-trisphosphate receptors are responsible for the Ca2+ release from
the ER. It comes as no surprise that this Ca2+ release from the ER and the
subsequent Ca2+ uptake at the mitochondria are finely regulated. Cancer cells
often modulate ER-Ca2+ transfer to the mitochondria in order to promote cell
survival and to inhibit cell death. Important regulators of these Ca2+ signals
and the onset of cancer are the B-cell lymphoma 2 (Bcl-2) family of proteins. An
increasing number of reports highlight the ability of these Bcl-2-protein family
members to finely regulate Ca2+ transfer from ER to mitochondria both in healthy
cells and in cancer. In this review, we focus on recent insights into the dynamic
regulation of ER-mitochondrial Ca2+ fluxes by Bcl-2-family members and how this
impacts cell survival, cell death and mitochondrial energy production.
PMID- 28516067
TI - COGNITOMICS: a new approach for the evaluation of the relationship between
diseases and cognition to be designed based on normal behavioral tendencies in
real life, a conceptual framework.
AB - The relationship between medical diseases and cognition has been a point of
interest in the last decades. In recent years studies in this field have
developed significantly applying various tools such as cognitive tests using
psychometric assessments and brain imaging techniques. The main focus of
cognitive function in this studies is the process through which this cognition is
obtained. It seems a novel methodology is needed while assessing the impact of
diseases such as diabetes on cognition based on heavenly religious teachings in
which cognition is believed to be the main source of human bliss and not just
some measurable quantitative components.
PMID- 28516064
TI - A Novel Role of Listeria monocytogenes Membrane Vesicles in Inhibition of
Autophagy and Cell Death.
AB - Bacterial membrane vesicle (MV) production has been mainly studied in Gram
negative species. In this study, we show that Listeria monocytogenes, a Gram
positive pathogen that causes the food-borne illness listeriosis, produces MVs
both in vitro and in vivo. We found that a major virulence factor, the pore
forming hemolysin listeriolysin O (LLO), is tightly associated with the MVs,
where it resides in an oxidized, inactive state. Previous studies have shown that
LLO may induce cell death and autophagy. To monitor possible effects of LLO and
MVs on autophagy, we performed assays for LC3 lipidation and LDH sequestration as
well as analysis by confocal microscopy of HEK293 cells expressing GFP-LC3. The
results revealed that MVs alone did not affect autophagy whereas they effectively
abrogated autophagy induced by pure LLO or by another pore-forming toxin from
Vibrio cholerae, VCC. Moreover, Listeria monocytogenes MVs significantly
decreased Torin1-stimulated macroautophagy. In addition, MVs protected against
necrosis of HEK293 cells caused by the lytic action of LLO. We explored the
mechanisms of LLO-induced autophagy and cell death and demonstrated that the
protective effect of MVs involves an inhibition of LLO-induced pore formation
resulting in inhibition of autophagy and the lytic action on eukaryotic cells.
Further, we determined that these MVs help bacteria to survive inside eukaryotic
cells (mouse embryonic fibroblasts). Taken together, these findings suggest that
intracellular release of MVs from L. monocytogenes may represent a bacterial
strategy to survive inside host cells, by its control of LLO activity and by
avoidance of destruction from the autophagy system during infection.
PMID- 28516065
TI - miR-142-5p Disrupts Neuronal Morphogenesis Underlying Porcine Hemagglutinating
Encephalomyelitis Virus Infection by Targeting Ulk1.
AB - Porcine hemagglutinating encephalomyelitis virus (PHEV) invades the central
nervous system (CNS) and causes neurodegenerative disease in suckling piglets,
but the understanding of its neuropathogenicity for neurological dysfunction
remains limited. Here, we report that miR-142-5p is localized to neurons and
negatively regulates neuronal morphogenesis in porcine hemagglutinating
encephalomyelitis (PHE). This phenotype was mediated by miR-142-5p inhibition of
an mRNA encoding unc-51-like-kinase1 (Ulk1), which controls axon outgrowth and
dendrite formation. Modulating miR-142-5p activity by microRNA mimics or
inhibitors induced neurodegeneration, including stunted axon elongation, unstable
dendritic spine formation, and irregular swelling and disconnection in neurites.
Relieving Ulk1 mRNA repression in primary cortical neurons by miR-142-5p
antagomirs or replication-deficient adenoviruses encoding Ulk1 (Ad5-Ulk1), which
improved rescue of nerve injury, restricted viral replication, and increased
survival rate in mice underlying PHEV infection. In contrast, disrupting Ulk1 in
RNAi-expressing neurons mostly led to significantly shortened axon elongation
and/or an abnormally large number of branched dendrites. Taken together, we
demonstrated that the abnormal neuronal morphogenesis underlying PHEV infection
was mainly caused by functional mRNA repression of the miR-142-5p target Ulk1.
Our data revealed that PHEV adapted to use spatiotemporal control of host
microRNAs to invade CNS, and provided new insights into the virus-associated
neurological dysfunction microenvironment.
PMID- 28516069
TI - Is it Necessary to Perform Nephrostography before Tube Removal after Percutaneous
Nephrolithotomy.
AB - BACKGROUND: The aim of this study is the caparison of the complications rate
among the patients which underwent nephrostomy removal with and without
performing nephrostography. MATERIALS AND METHODS: Between October 2010 and
November 2011, 200 patients who underwent standard percutaneous nephrolithotomy
(PCNL) procedures were included in this study. The patients were randomly
assigned into two groups, Group A (n = 100) did not undergo the antegrade
nephrostography on postoperative day 2 and the patients were discharged keeping
the nephrostomy until postoperative day 3, while in Group B (n = 100) the
nephrostomy tube was removed on postoperative day 3 after antegrade
nephrostography demonstrating ureteral drainage down to the bladder.
Postoperative complications in both groups were recorded and compared between two
groups. RESULTS: A total of 200 patients were treated with standard PCNL. The
persistent leakage of urine after removal of the nephrostomy tube was encountered
in 5 (5.0%) and 3 (3%) of patients in Groups 1 and 2, respectively. Urinary
leakage was resolved with conservative management in 3 and 2 patients of Groups 1
and 2, respectively, but a double-J stent was inserted in 2 and 1 patients in
each group because of persistent leakage of urine more than 1-week. The two
groups show comparable complications such as prolonged urinary leakage which
managed in a similar manner, however, postoperative hospital stay was lesser in
Group 1. CONCLUSION: Our results revealed postoperative performing nephrostogramy
before tube removal changed the planning of complications such as prolonged
urinary leakage and could be omitted in cases.
PMID- 28516068
TI - A Comparison of Betamethasone Valerate 0.1% Cream Twice Daily Plus Oral
Simvastatin Versus Betamethasone Valerate 0.1% Cream Alone in the Treatment of
Vitiligo Patients.
AB - BACKGROUND: Vitiligo, a common disorder of depigmentation, is often difficult to
treat. Corticosteroids are known to be effective, but with modest results.
Although simvastatin has been reported to be effective for immunorelated
dermatologic disorders including vitiligo, controlled trials are lacking. This
study was conducted to compare the efficacy of topical betamethasone valerate
0.1% cream (as a standard method of treatment for vitiligo) versus a combination
of betamethasone valerate plus oral simvastatin in the treatment of vitiligo.
MATERIALS AND METHODS: Eighty-eight subjects with symmetric vitiligo who had body
surface involvement up to 20% were divided randomly into two groups. Group A were
treated with betamethasone valerate 01% cream twice daily and Group B with
betamethasone valerate 01% cream twice daily and oral simvastatin 80 mg daily for
12 weeks. Finally, 46 patients completed treatment after 12 weeks in both groups.
The results were evaluated by a blind dermatologist using Vitiligo Area Scoring
Index (VASI) score at baseline, 4th, 8th, and 12th week of treatment. In a
similar way, subjective assessment performed by patients based on photo
evaluation at the end of the study. RESULTS: Despite a continuous reduction in
VASI score in both groups, according to both physician (P = 0.13) and patient (P
= 0.374) assessment oral simvastatin was not statistically more effective than
conventional treatment of vitiligo. CONCLUSION: This study indicates that oral
simvastatin is not associated with significant impacts in the treatment of
vitiligo as compared to other inflammatory dermatologic conditions such as
psoriasis. Indeed, other studies should be initiated regarding exact molecular
and cellular effects of statins in the treatment of vitiligo.
PMID- 28516066
TI - The Alpha-Tocopherol Form of Vitamin E Boosts Elastase Activity of Human PMNs and
Their Ability to Kill Streptococcus pneumoniae.
AB - Despite the availability of vaccines, Streptococcus pneumoniae remains a leading
cause of life-threatening infections, such as pneumonia, bacteremia and
meningitis. Polymorphonuclear leukocytes (PMNs) are a key determinant of disease
course, because optimal host defense requires an initial robust pulmonary PMN
response to control bacterial numbers followed by modulation of this response
later in infection. The elderly, who manifest a general decline in immune
function and higher basal levels of inflammation, are at increased risk of
developing pneumococcal pneumonia. Using an aged mouse infection model, we
previously showed that oral supplementation with the alpha-tocopherol form of
vitamin E (alpha-Toc) decreases pulmonary inflammation, in part by modulating
neutrophil migration across lung epithelium into alveolar spaces, and reverses
the age-associated decline in resistance to pneumococcal pneumonia. The objective
of this study was to test the effect of alpha-Toc on the ability of neutrophils
isolated from young (22-35 years) or elderly (65-69 years) individuals to migrate
across epithelial cell monolayers in response to S. pneumoniae and to kill
complement-opsonized pneumococci. We found that basal levels of pneumococcal
induced transepithelial migration by PMNs from young or elderly donors were
indistinguishable, suggesting that the age-associated exacerbation of pulmonary
inflammation is not due to intrinsic properties of PMNs of elderly individuals
but rather may reflect the inflammatory milieu of the aged lung. Consistent with
its anti-inflammatory activity, alpha-Toc treatment diminished PMN migration
regardless of donor age. Unexpectedly, unlike previous studies showing poor
killing of antibody-opsonized bacteria, we found that PMNs of elderly donors were
more efficient at killing complement-opsonized bacteria ex vivo than their
younger counterparts. We also found that the heightened antimicrobial activity in
PMNs from older donors correlated with increased activity of neutrophil elastase,
a serine protease that is required to kill pneumococci. Notably, incubation with
alpha-Toc increased PMN elastase activity from young donors and boosted their
ability to kill complement-opsonized pneumococci. These findings demonstrate that
alpha-Toc is a potent modulator of PMN responses and is a potential nutritional
intervention to combat pneumococcal infection.
PMID- 28516070
TI - Bone Density in Postmenopausal Women with or without Breast Arterial
Calcification.
AB - BACKGROUND: Identification of osteoporosis in women in order to prevent its
related morbidity and mortality is considered a priority. Routine mammography is
performed on all menopausal women as a screening tool. Determination of the
relation between breast arterial calcification (BAC) on mammography and the bone
density of this high-risk population could help us to determine those with
osteoporosis. The aim of this study was to investigate the mentioned probable
relation between BAC and osteoporosis. MATERIALS AND METHODS: In this cross
sectional study, menopausal women referred for annual screening mammography were
enrolled. According to the results of mammography, they were classified into two
groups: menopausal women with and without calcification of breast arteries. The
selected women were referred for bone mineral density (BMD) evaluation by dual
energy x-ray absorptiometry (DXA). The results of BMD were compared between the
two studied groups. RESULTS: In this study, BMD was measured in 43 and 45
menopausal women with and without BAC, respectively. After age adjustment the
difference between BMD measurements were not statistically significantly
different (P > 0.05). There was a significant negative correlation between age
and lumbar (P = 0.002, r = -0.42) and hip bone (P = 0.000, r = -0.67) density in
menopausal women with BAC. CONCLUSION: The results of the current study indicated
that there was no significant relationship between BAC and BMD in our studied
population, but it seems that increasing age has an important role in both
developing BAC and reducing BMD. For obtaining more conclusive results, further
studies with larger sample sizes and considering the severity of BAC is
recommended.
PMID- 28516071
TI - Levamisole as an Adjuvant to Short-Course Therapy in Newly Diagnosed Pulmonary
Tuberculosis Patients.
AB - BACKGROUND: The estimated incidence and prevalence of tuberculosis in India are
2.1 and 2.6 million cases respectively. Immunotherapy may shorten tuberculosis
treatments and improve the immunity of individuals as well. Hence we study the
efficacy of levamisole (LVM) (immunomodulator) as an adjuvant to chemotherapy of
pulmonary tuberculosis patients. MATERIALS AND METHODS: A randomized, double
blind, placebo-controlled clinical trial was conducted for 21 months in newly
diagnosed sputum positive pulmonary tuberculosis patients. Patients were
subjected initially to clinical examination, sputum acid-fast bacilli smear and
culture, tuberculin skin test and weight record. During follow-up, above
investigations were repeated. Sixty-five patients were randomly assigned into two
groups to receive either tab LVM 100 mg once in a day or matching placebo, orally
as a single dose, thrice a week, for 2 months with short-course antituberculosis
chemotherapy. RESULTS: Sputum negativity at 1 week was observed in 11 (44%)
patients in LVM group whereas only 3 (12%) in placebo group. All the patients 25
(100%) in LVM group were sputum negative compared to 14 (56%) in placebo group by
the end of 3 weeks. In LVM group, 24 (96%) and 11 (44%) patients in placebo group
show radiological improvement at 2 months. A direct correlation existed between
quantum of immune response and weight gain with LVM. LVM rendered all anergic
patients to positive tuberculin reactors. In LVM group, patients with initial
Mantoux >=20 mm and advanced cavitary disease, there was decrease in tuberculin
reaction size. CONCLUSION: Adjuvant immunomodulation with levamisole has the
potential of shortening the total duration of antitubercular therapy.
PMID- 28516072
TI - Bevacizumab in Recurrent Glioma: Patterns of Treatment Failure and Implications.
AB - Glioblastoma, the most common primary malignant brain tumor in adults, is highly
aggressive and associated with a poor prognosis. Bevacizumab, a monoclonal
antibody against the vascular endothelial growth factor receptor, has
increasingly been used in the treatment of recurrent glioblastoma. It has
achieved excellent rates of radiographic response, but most patients will
progress after only a few months. Upon recurrence, tumors may not enhance,
secondary to vascular normalization. We describe four patterns of radiographic
progression commonly associated with Bevacizumab failure: 1) Distant enhancing
tumor, 2) Local tumor progression without enhancement, 3) Diffuse gliomatosis
like infiltration, and 4) Local or multifocal progression, with enhancement. Some
have noted an increased incidence of distant or diffuse disease upon recurrence,
suggestive of a transition to a more aggressive phenotype, but a review of the
literature suggests there is no conclusive evidence that Bevacizumab treatment is
associated with an increased rate of distant or diffuse recurrence.
PMID- 28516074
TI - An Updated Nationwide Epidemiology of Primary Brain Tumors in Republic of Korea,
2013.
AB - BACKGROUND: This report aims to provide accurate nationwide epidemiologic data on
primary brain and central nervous system (CNS) tumors in the Republic of Korea.
We updated the data by analyzing primary brain and CNS tumors diagnosed in 2013
using the data from the national cancer incidence database. METHODS: Data on
primary brain and CNS tumors diagnosed in 2013 were collected from the Korean
Central Cancer Registry. Crude and age-standardized rates were calculated in
terms of gender, age, and histological type. RESULTS: A total of 11,827 patients
were diagnosed with primary brain and CNS tumors in 2013. Brain and CNS tumors
occurred in females more often than in males (female:male, 1.70:1). The most
common tumor was meningioma (37.3%). Pituitary tumors (18.0%), gliomas (12.7%),
and nerve sheath tumors (12.3%) followed in incidence. Glioblastomas accounted
for 41.8% of all gliomas. In children (<19 years), sellar region tumors
(pituitary and craniopharyngioma), embryonal/primitive/medulloblastoma, and germ
cell tumors were the most common tumors. CONCLUSION: This study should provide
valuable information regarding the primary brain tumor epidemiology in Republic
of Korea.
PMID- 28515670
TI - Measurement of the W boson polarisation in [Formula: see text] events from pp
collisions at [Formula: see text] = 8 TeV in the lepton + jets channel with
ATLAS.
AB - This paper presents a measurement of the polarisation of W bosons from [Formula:
see text] decays, reconstructed in events with one high-[Formula: see text]
lepton and at least four jets. Data from pp collisions at the LHC were collected
at [Formula: see text] = 8 TeV and correspond to an integrated luminosity of 20.2
fb[Formula: see text]. The angle [Formula: see text] between the b-quark from the
top quark decay and a direct W boson decay product in the W boson rest frame is
sensitive to the W boson polarisation. Two different W decay products are used as
polarisation analysers: the charged lepton and the down-type quark for the
leptonically and hadronically decaying W boson, respectively. The most precise
measurement of the W boson polarisation via the distribution of [Formula: see
text] is obtained using the leptonic analyser and events in which at least two of
the jets are tagged as b-quark jets. The fitted fractions of longitudinal, left-
and right-handed polarisation states are [Formula: see text], [Formula: see text]
and [Formula: see text], and are the most precisely measured W boson polarisation
fractions to date. Limits on anomalous couplings of the Wtb vertex are set.
PMID- 28516073
TI - Systematic Analysis of Clinical Outcomes Following Stereotactic Radiosurgery for
Central Neurocytoma.
AB - Central neurocytoma (CN) typically presents as an intraventricular mass causing
obstructive hydrocephalus. The first line of treatment is surgical resection with
adjuvant conventional radiotherapy. Stereotactic radiosurgery (SRS) was proposed
as an alternative therapy for CN because of its lower risk profile. The objective
of this systematic analysis is to assess the efficacy of SRS for CN. A systematic
analysis for CN treated with SRS was conducted in PubMed. Baseline patient
characteristics and outcomes data were extracted. Heterogeneity and publication
bias were also assessed. Univariate and multivariate linear regressions were used
to test for correlations to the primary outcome: local control (LC). The
estimated cumulative rate of LC was 92.2% (95% confidence interval: 86.5-95.7%,
p<0.001). Mean follow-up time was 62.4 months (range 3-149 months). Heterogeneity
and publication bias were insignificant. The univariate linear regression models
for both mean tumor volume and mean dose were significantly correlated with
improved LC (p<0.001). Our data suggests that SRS may be an effective and safe
therapy for CN. However, the rarity of CN still limits the efficacy of a
quantitative analysis. Future multi-institutional, randomized trials of CN
patients should be considered to further elucidate this therapy.
PMID- 28516075
TI - Fourth Ventricular Lesions in Metastatic Gliomas: A Rare Predilection?
AB - Over the course of five years, a total of ten cases were collected of glioma
patients in whom a distant lesion at the fourth ventricle was noted. A 'distant
lesion' was defined as a lesion with a normal appearing tissue bridge at imaging
between the primary and secondary locations. Previous imaging of these patients
was reviewed along with clinical history, course of therapy, and available
histology. A review of the literature was performed with respect to present
knowledge on patterns of glioma proliferation and dissemination. This case series
is the first to describe the fourth ventricle as a location that may be prone to
secondary lesions in glioma patients. Further investigation on this subject may
yield deeper insights into the mechanisms by which glial tumors spread within the
brain, with the hope of developing or improving therapeutic targets.
PMID- 28516076
TI - Primary Central Nervous System Vasculitis Mimicking a Cortical Brain Tumor: A
Case Report.
AB - We report a case of primary central nervous system vasculitis (PCNSV) mimicking a
cortical brain tumor. A 25-year-old woman presented with a 2-week history of
headache and transient right hemiparesis. Brain magnetic resonance imaging (MRI)
revealed a cortical-involving lesion on the left frontal lobe. The 6-cm sized
lesion showed low signal intensity on T1-weighted images and high signal
intensity on T2-weighted images. The lesion had continual linear enhancement on
the subcortical white matter and leptomeninges. There was no evidence of
hemorrhage on susceptibility-weighted images and no diffusion restriction on
diffusion-weighted images. The regional cerebral blood volume was decreased on
the MR perfusion images, and spectroscopy showed increased lactate and lipid
peaks. The symptoms were aggravated by fever and seizures. Biopsy was performed
to rule out tumorous or inflammatory lesions. Pathologically, lymphocytes were
infiltrated on the vessels, and the arachnoid membrane was thickened with
inflammatory cells. The patient did not have any underlying diseases, including
immune disorders. After high-dose steroid administration, her symptoms improved.
Two months later, brain MRI showed a reduction in the infiltration of the T2
hyperintensity lesion with subtle subcortical enhancement. We present a case of
PCNSV involving the left frontal lobe, showing vasogenic edema, mass effect, and
subcortical linear contrast enhancement without hemorrhage or infarction.
PMID- 28516077
TI - Toxoplasmic Encephalitis in Patient with Acquired Immunodeficiency Syndrome.
AB - Toxoplasmic encephalitis (TE) is an opportunistic infection found in
immunocompromised patients and TE related cerebral mass lesion is often reported
in acquired immunodeficiency acquired immunodeficiency syndrome (AIDS) patients.
However, incidence of TE related AIDS in Korea is still rare and is unfamiliar to
neurosurgeons. Differential diagnosis is needed to rule out other brain lesions.
A 39-year-old man visited the emergency room with rapid progressive left
hemiparesis. Magnetic resonance imaging showed a ring-enhanced mass lesion in his
right frontal lobe. Human immunodeficiency virus and Toxoplasma gondii
immunoglobulin G were tested positive by a serologic test. We report here a rare
case of patient with TE related AIDS.
PMID- 28516079
TI - Fourth Ventricle Neurenteric Cyst Mimicking Hemangioblastoma.
AB - This report presents a case of fourth ventricle neurenteric cyst (NE cyst)
mimicking hemangioblastoma, which developed in a 50-year-old woman. A tiny
enhancing mural portion of the fourth ventricle in MRI suggested that the cyst
was hemangioblastoma, but pathological evidence showed that the cyst was in fact
NE cyst in the fourth ventricle. In order to make proper decision on to what
extent of surgical resection should be done, considering every possibility in
differential diagnosis might be helpful. This case reports an unusual pathology
in 4th ventricle, considering the patient's age, and demonstrates that a rarer
disease may share radiological features of a common disease.
PMID- 28516084
TI - Editorial: Health Disparities-An Important Public Health Policy Concern.
PMID- 28516078
TI - Subependymal Giant Cell Astrocytoma Presenting with Tumoral Bleeding: A Case
Report.
AB - We report a rare case of subependymal giant cell astrocytoma (SEGA) associated
with tumoral bleeding in a pediatric patient without tuberous sclerosis complex
(TSC). A 10-year-old girl presented with a 2-week history of an increasingly
aggravating headache. Brain magnetic resonance imaging revealed an approximately
3.6-cm, well-defined, heterogeneously enhancing mass with multistage hemorrhages
on the right-sided foramen of Monro. The tumor was completely resected using a
transcallosal approach. Intraoperatively, the mass presented as a gray-colored
firm tumor associated with acute and subacute hemorrhages. The origin of the mass
was identified as the ventricular septum adjacent to the foramen of Monro. A
pathological analysis revealed pleomorphic multinucleated eosinophilic tumor
cells with abundant cytoplasm. These cells showed positive staining for the glial
fibrillary acidic protein and S100 protein. A diagnosis of SEGA was established.
The patient recovered without any neurological symptoms. There was no evidence of
TSC. The radiological follow-up showed no recurrence for 2 years. This was a case
of SEGA with intratumoral hemorrhage, for which a favorable outcome was achieved,
without any neurological deficit after tumoral resection.
PMID- 28516080
TI - Cutaneous Anaplastic Large T-Cell Lymphoma with Invasion of the Central Nervous
System: A Case Report.
AB - Anaplastic large T-cell lymphoma (ALCL) encompasses different clinical entities
that can be aggressive or localized. Scalp anaplastic lymphoma kinase (ALK)
negative ALCL is considered a localized lymphoma, and usually extends to the
regional lymph nodes; intracranial invasion is rare. A 74-year-old woman was
diagnosed with scalp ALK-negative ALCL, but did not exhibit invasion of the lymph
nodes. Computed tomography and magnetic resonance imaging revealed intracranial
masses with bony erosions. We treated the patient using CHOP chemotherapy and
achieved short-term regression of the scalp and intracranial lesions. However,
the patients ultimately died of pneumonia during the pancytopenic period.
Therefore, caution must be exercised when treating scalp ALK-negative ALCL with
intracranial invasion.
PMID- 28516081
TI - A Case of Coincidental Intrasellar Chordoma and Pituitary Adenoma.
AB - Although chordomas are midline tumors, primarily intrasellar chordomas are
extremely rare. In this report, the authors describe the case of a 68-year-old
female with partial abducens nerve palsy in the right eye due to the intrasellar
cystic tumor. After endonasal trans-sphenoidal surgery, intraoperative and
histopathological findings confirmed the co-occurrence of an entirely intrasellar
chordoma and pituitary adenoma. To our knowledge, the present case is the third
reported case of an intrasellar chordoma with a pituitary adenoma.
PMID- 28516082
TI - Multifocal Recurrent Osteomyelitis and Hemophagocytic Lymphohistiocytosis in a
Boy with Partial Dominant IFN-gammaR1 Deficiency: Case Report and Review of the
Literature.
AB - Mutations in the genes coding for cytokines, receptors, second messengers, and
transcription factors of interferon gamma (IFN-gamma) immunity cause Mendelian
susceptibility to mycobacterial disease (MSMD). We report the case of a 7-year
old male patient with partial dominant (PD) IFN-gamma receptor 1 deficiency who
had suffered from multifocal osteomyelitis attributable to bacille Calmette
Guerin vaccination since the age of 18 months. He developed hemophagocytic
lymphohistiocytosis (HLH), a hyper-inflammatory complication, and died with
multiorgan dysfunction, despite having been diagnosed and treated relatively
early. Patients with PD IFN-gammaR1 deficiency usually have good prognosis and
might respond to human recombinant subcutaneous IFN-gamma. Several monogenic
congenital defects have been linked to HLH, a catastrophic "cytokine storm" that
is usually ascribed to lymphocyte dysfunction and thought to be triggered by
interferon gamma. This is the sixth patient with both MSMD and HLH of whom we are
aware. The fact that patients with macrophages that cannot respond to IFN-gamma
still develop HLH, bring these assumptions into question.
PMID- 28516083
TI - How to Study Chronic Diseases-Implications of the Convention on the Rights of
Persons with Disabilities for Research Designs.
AB - BACKGROUND: The Convention on the Rights of Persons with Disabilities (CRPD) has
been received considerable attention internationally. METHODS: The Convention's
main arguments are conceptually analyzed. Implications for the development of
research designs are elaborated upon. RESULTS: The Convention entails both a
human rights and a sociopolitical dimension. Advancing a relational notion of
disability, it enters a rather foreign terrain to medical sciences. Research
designs have to be changed accordingly. CONCLUSION: Research designs in
accordance with the CRPD should employ and further develop context-sensitive
research strategies and interdisciplinary collaboration. Complex designs that
allow for a relational analysis of personalized effects have to be established
and evaluated, thereby systematically integrating qualitative methods.
PMID- 28516089
TI - Distinguished Lecture Given at the Opening of the 5th International Meeting on
Aortic Disease, Liege, Belgium (September 15, 2016).
PMID- 28516087
TI - DNA Sequence Analysis in Clinical Medicine, Proceeding Cautiously.
AB - Delineation of underlying genomic and genetic factors in a specific disease may
be valuable in establishing a definitive diagnosis and may guide patient
management and counseling. In addition, genetic information may be useful in
identification of at risk family members. Gene mapping and initial genome
sequencing data enabled the development of microarrays to analyze genomic
variants. The goal of this review is to consider different generations of
sequencing techniques and their application to exome sequencing and whole genome
sequencing and their clinical applications. In recent decades, exome sequencing
has primarily been used in patient studies. Discussed in some detail, are
important measures that have been developed to standardize variant calling and to
assess pathogenicity of variants. Examples of cases where exome sequencing has
facilitated diagnosis and led to improved medical management are presented. Whole
genome sequencing and its clinical relevance are presented particularly in the
context of analysis of nucleotide and structural genomic variants in large
population studies and in certain patient cohorts. Applications involving
analysis of cell free DNA in maternal blood for prenatal diagnosis of specific
autosomal trisomies are reviewed. Applications of DNA sequencing to diagnosis and
therapeutics of cancer are presented. Also discussed are important recent
diagnostic applications of DNA sequencing in cancer, including analysis of tumor
derived cell free DNA and exosomes that are present in body fluids. Insights
gained into underlying pathogenetic mechanisms of certain complex common
diseases, including schizophrenia, macular degeneration, neurodegenerative
disease are presented. The relevance of different types of variants, rare,
uncommon, and common to disease pathogenesis, and the continuum of causality, are
addressed. Pharmogenetic variants detected by DNA sequence analysis are gaining
in importance and are particularly relevant to personalized and precision
medicine.
PMID- 28516090
TI - Lower Aorto-Iliac Bifurcation Position and Incident Cardiovascular Disease: A
Multi-Ethnic Study of Atherosclerosis (MESA).
AB - BACKGROUND: With increasing age, a downward shift of the aorto-iliac bifurcation
relative to the lumbar spine occurs. A lower bifurcation position is an
independent marker for adverse vascular aging and is associated with increased
burden of cardiovascular disease (CVD) risk factors; however, the associations
between lower bifurcation position and CVD events remain unknown. METHODS:
Abdominal computed tomography scans were used to measure the aorto-iliac
bifurcation distance (AIBD, distance from the aorto-iliac bifurcation to the
L5/S1 disc space). Cox proportional hazard analysis was used to determine the
independent hazard of a lower bifurcation position (smaller AIBD) for incident
coronary heart disease (CHD, defined as myocardial infarction, resuscitated
cardiac arrest, or sudden cardiac death), CVD (CHD plus stroke or stroke death),
and all-cause mortality (ACM). RESULTS: In the 1,711 study participants (51%
male), the mean AIBD was 26 +/- 15 mm. After a median follow-up of 10 years, 63
(3.7%) developed CHD, 100 (5.8%) developed CVD, and 129 (7.5%) were deceased.
Compared to the 4th quartile of AIBD (highest bifurcation position), participants
in the 1st quartile (lowest bifurcation position) had increased risk for CHD
(hazard ratio (HR) = 1.5, 95% confidence interval (CI): 0.8-3.0, P = 0.2), CVD
(HR = 1.8, 95% CI: 0.9-2.7, P = 0.1), and ACM (HR = 2.2, 95% CI: 1.3-3.6, P =
0.01). After adjustments for CVD risk factors, the HR for ACM was no longer
significant. CONCLUSION: Despite being an independent marker for adverse vascular
changes in the aorta, a lower aorto-iliac bifurcation position was not
independently associated with future CVD events. The opposing effects of
atherosclerosis and stiffness in the aorta may, in part, explain our null
findings.
PMID- 28516085
TI - Analysis of Septin Reorganization at Cytokinesis Using Polarized Fluorescence
Microscopy.
AB - Septins are conserved filament-forming proteins that act in diverse cellular
processes. They closely associate with membranes and, in some systems, components
of the cytoskeleton. It is not well understood how filaments assemble into higher
order structures in vivo or how they are remodeled throughout the cell cycle. In
the budding yeast S. cerevisiae, septins are found through most of the cell cycle
in an hourglass organization at the mother-bud neck until cytokinesis when the
collar splits into two rings that disassemble prior to the next cell cycle.
Experiments using polarized fluorescence microscopy have suggested that septins
are arranged in ordered, paired filaments in the hourglass and undergo a
coordinated 90 degrees reorientation during splitting at cytokinesis. This
apparent reorganization could be due to two orthogonal populations of filaments
disassembling and reassembling or being preferentially retained at cytokinesis.
In support of this idea, we report a decrease in septin concentration at the
mother-bud neck during cytokinesis consistent with other reports and the timing
of the decrease depends on known septin regulators including the Gin4 kinase. We
took a candidate-based approach to examine what factors control reorientation
during splitting and used polarized fluorescence microscopy to screen mutant
yeast strains deficient in septin interacting proteins. Using this method, we
have linked known septin regulators to different aspects of the assembly,
stability, and reorganization of septin assemblies. The data support that ring
splitting requires Gin4 activity and an anillin-like protein Bud4, and normal
accumulation of septins at the ring requires phosphorylation of Shs1. We found
distinct regulatory requirements for septin organization in the hourglass
compared to split rings. We propose that septin subpopulations can vary in their
localization and assembly/disassembly behavior in a cell-cycle dependent manner
at cytokinesis.
PMID- 28516093
TI - Iatrogenic Supravalvular Aortic Stenosis.
AB - We describe a case of hemolytic anemia and proximal anastomotic site stenosis
following emergency repair of a Type A aortic dissection. This rare complication
led to a reoperation to correct the iatrogenic aortic stenosis and cure the
consequent hemolysis. A "sandwich" technique (with two Teflon strips on the
outside and inside of the aortic wall) was used in the initial repair to
reinforce the suture line and prevent bleeding from the aortic anastomoses. At
the time of reoperation, the inner Teflon strip at the proximal aortic
anastomosis was found to have inverted into the aortic lumen, as suggested by the
preoperative magnetic resonance imaging. Surgical treatment consisted of
resecting the portion of inner Teflon that had turned in and tacking the
remaining part back onto the aortic wall. The observed hemolysis was likely due
to the turbulent flow associated with the supra-aortic stenosis and the collision
of red cells with the internal Teflon strip. The patient made an uncomplicated
recovery with no further hemolysis and was discharged on postoperative day 8.
PMID- 28516094
TI - Combined Transapical Transcatheter Aortic Valve Replacement and Thoracic
Endovascular Aortic Repair for Severe Aortic Stenosis and Arch Aneurysm.
AB - An 83-year-old male with multiple comorbidities presented with critical aortic
stenosis and a saccular aortic arch aneurysm. Through a mini thoracotomy, a
balloon expandable transcatheter aortic valve was delivered transapically. A
thoracic stent graft was then delivered through the prosthetic valve and deployed
in the arch, while a covered stent was deployed in the left common carotid
artery. Three-year postoperative computed tomography showed a thrombosed arch
aneurysm with decreased size. This case demonstrates the feasibility of using
combined transapical transcatheter technologies to treat multicomponent disease
in a high-risk patient during a single operation.
PMID- 28516088
TI - The Candida albicans Biofilm Matrix: Composition, Structure and Function.
AB - A majority of infections caused by Candida albicans-the most frequent fungal
pathogen-are associated with biofilm formation. A salient feature of C. albicans
biofilms is the presence of the biofilm matrix. This matrix is composed of
exopolymeric materials secreted by sessile cells within the biofilm, in which all
classes of macromolecules are represented, and provides protection against
environmental challenges. In this review, we summarize the knowledge accumulated
during the last two decades on the composition, structure, and function of the C.
albicans biofilm matrix. Knowledge of the matrix components, its structure, and
function will help pave the way to novel strategies to combat C. albicans biofilm
infections.
PMID- 28516095
TI - David-V Procedure in a Patient with Aortic Dilation and Competent Quadricuspid
Aortic Valve: Are Genetics to Blame?
AB - Quadricuspid aortic valves (QAVs) are extremely rare. In this case study, we
report a David-V valve-sparing aortic root replacement with reimplantation of a
native QAV in a patient with aortic dilation, normal valve function, and a family
history of aortic dissection. Microscopic pathological examination of the excised
section of the aorta revealed scattered small foci of cystic medical degeneration
throughout. A genetic predisposition for aortic dilation may be present in
patients with QAV, even in the setting of a competent valve. Regular screening
for aortic dilation in patients with known QAV should therefore be considered.
PMID- 28516091
TI - Treatment of Dacron Grafting Dilatation with Endovascular Stent Grafting.
AB - Dacron grafts are frequently used during surgical revascularization procedures.
Complications including graft thrombosis and infection are well known; however,
aneurysm formation is extremely rare. In this report, we describe dilatation of a
Dacron graft detected four years after aortobifemoral bypass procedure in a 50
year-old male patient who was treated with endovascular stent grafting.
PMID- 28516092
TI - Frozen Elephant Trunk and Antegrade Visceral Debranching in the Surgical
Treatment of Type B Aortic Dissection: An Alternative Method.
AB - Intervention is inevitable in complicated Type B aortic dissections. Classical
surgical procedures and endovascular interventions are far from ideal treatments
due to their high risk of periprocedural complications and mortality. There is
often a need for alternative method in cases of difficult anatomy. We present the
combined use of frozen elephant trunk and antegrade visceral debranching methods
in the treatment of a 54-year-old male patient with complicated Type B aortic
dissection.
PMID- 28516096
TI - Page for the General Public.
PMID- 28516086
TI - Can Synovial Pathobiology Integrate with Current Clinical and Imaging Prediction
Models to Achieve Personalized Health Care in Rheumatoid Arthritis?
AB - Although great progress has been made in the past decade toward understanding the
pathogenesis of rheumatoid arthritis (RA), clinicians remain some distance from a
goal of personalized health care. The capacity to diagnose RA early, predict
prognosis, and moreover predict response to biologic therapies has been a
research focus for many years. How currently available clinical prediction models
can facilitate such goals is reviewed in this article. In addition, the role of
current imaging techniques in this regard is also discussed. Finally, the authors
review the current literature regarding synovial biomarkers and consider whether
integration of synovial pathobiology into clinical prediction algorithms may
enhance their predictive value.
PMID- 28516097
TI - Asymmetric Dimethylarginine in Patients with Ascending Aortic Aneurysms.
AB - BACKGROUND: Ascending thoracic aortic aneurysm (aTAA) is a heterogeneous group of
disorders that involve impaired endothelial function. The nitric oxide (NO)
synthase inhibitor asymmetric dimethylarginine (ADMA) serves as an endothelial
dysfunction marker. Thus, we investigated ADMA levels in patients with aTAA.
METHODS: Eighty-six patients with aTAA and 18 healthy individuals were enrolled.
All patients underwent echocardiography. Plasma ADMA levels were measured using
high-performance liquid chromatography. RESULTS: ADMA levels were higher in aTAA
patients than in control patients (p = 0.034). According to the multivariable
regression model, higher ADMA levels were associated with ascending aortic
diameter (p = 0.017), smoking (p = 0.016), and log-transformed estimated
glomerular filtration rate (eGFR, p = 0.005). CONCLUSION: This pilot study
demonstrates an association of ADMA with ascending aortic dilatation; however,
further studies are needed to investigate whether increased ADMA levels underlie
aTAA development.
PMID- 28516098
TI - Spontaneous Regression of a Large Iatrogenic Dissection of the Ascending Aorta.
AB - A 74-year-old woman was admitted for right coronary angioplasty. During the
procedure, she complained about chest pain, and contrast injection showed an
iatrogenic dissection of the ascending aorta. A contrast computed tomography (CT)
scan confirmed the diagnosis via visualization of a large non-circulating false
lumen, which involved nearly the entire ascending aorta. The patient remained
hemodynamically stable and asymptomatic while receiving medical therapy alone.
Another CT scan performed 3 days later showed complete regression of the false
lumen. This case suggests that uncomplicated iatrogenic dissection of the
ascending aorta, even when large, may be managed successfully by medical therapy.
PMID- 28516099
TI - Conservative Management of Extensive Iatrogenic Aortic Dissection.
AB - Iatrogenic aortic dissection (IAD) is a rare complication of percutaneous
coronary interventions (PCI). There are no clear guidelines for IAD management,
and limited data are available. Registry data and case series combined with
extrapolations from our experience with spontaneous Type-A dissections suggest
that very limited dissections are often managed conservatively with coronary
stenting of the entry tear when possible, while more extensive dissections are
managed surgically. We present a case report of a 50-year-old woman who underwent
PCI for an ST-elevation myocardial infarction that resulted in an extensive IAD
from the ostium of the right coronary artery to the aortic root, ascending aorta,
and aortic arch. While the current evidence strongly supports surgical management
of such extensive dissection, our patient was successfully managed conservatively
with complete resolution according to short-term computed tomography imaging.
This case suggests that conservative management may be a reasonable approach for
select patients with extensive IAD.
PMID- 28516100
TI - Transient Aortic Intramural Hematoma Complicating Transaortic Valve Replacement.
AB - Acute aortic intramural hematoma, which is a variant of acute aortic syndromes,
most frequently occurs spontaneously and typically is treated similar to classic
aortic dissection. Here, we describe a case in which an iatrogenic aortic
intramural hematoma occurs shortly after transaortic valve replacement. The
patient was managed conservatively, and the hematoma quickly resolved as
demonstrated by serial imaging.
PMID- 28516101
TI - Early Spontaneous Resolution of an Iatrogenic Acute Type A Aortic Dissection.
AB - Acute aortic dissection is a rare but devastating complication during cardiac
catheterization. We present the case of an elderly female who incurred a Stanford
Type A/DeBakey Type I acute aortic dissection extending into the arch vessels and
descending aorta likely occurring during right coronary artery engagement for
angioplasty. The patient was treated successfully by immediately sealing the
entrance of the dissection via the placement of a stent and anti-impulse therapy.
Follow-up computed tomography scan showed complete resolution of the dissection
within one month.
PMID- 28516102
TI - Iatrogenic Aortic Dissection: Review of the Literature.
PMID- 28516103
TI - Simplified Approach for Repair of Early Pseudoaneurysm of the Left Coronary
Button Following Composite Graft Due to Acute Type A Aortic Dissection.
AB - We present a simplified surgical technique that was performed on a 37-year-old
man who presented with a pseudoaneurysm of the left coronary ostium two months
after repair of acute Type A aortic dissection with a composite graft.
Intraoperatively, the surgical sites showed extreme adhesions. The leakage at the
level of the coronary suture line was exposed from inside the aortic graft.
Repair was performed using 7.0 polypropylene sutures, and the postoperative
course was uneventful. The patient was discharged on postoperative day six
without further complications.
PMID- 28516104
TI - Minimalist' Trans-Aneurysmal Approach to Coronary Button Pseudoaneurysm.
PMID- 28516105
TI - Page for the General Public.
PMID- 28516106
TI - A Cost-Effectiveness Analysis of Surgical Treatment Modalities for Chondral
Lesions of the Knee: Microfracture, Osteochondral Autograft Transplantation, and
Autologous Chondrocyte Implantation.
AB - BACKGROUND: Numerous surgical options exist to treat chondral lesions in the
knee, including microfracture (MFx), osteochondral autograft transplantation
(OAT), first-generation autologous chondrocyte implantation (ACI-1), and next
generation ACI (ACI-2). PURPOSE: To compare the cost-effectiveness of MFx, OAT,
and ACI-1. The secondary purpose of this study was to compare the functional
outcomes of MFx, OAT, ACI-1, and ACI-2. STUDY DESIGN: Systematic review; Level of
evidence, 2. METHODS: Two independent reviewers conducted an online literature
search of 2 databases for level 1 and 2 studies using the Lysholm, International
Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score
(KOOS), and/or Hospital for Special Surgery (HSS) Knee Score. A weighted mean
difference in pre- to postoperative functional outcome score was calculated for
each treatment. The mean per-patient costs associated with MFx, OAT, and ACI-1
were determined from a recent publication based on review of a national private
insurance database. The cost for each procedure was then divided by the weighted
mean difference in functional outcome score to give the cost-per-point change in
outcome score. RESULTS: A total of 12 studies (6 level 1, 6 level 2) met the
inclusion criteria for the functional outcome analysis, including 730 knees (MFx,
n = 300; OAT, n = 90; ACI-1, n = 68; ACI-2, n = 272). The mean follow-up was not
significantly different between groups (MFx, 29.4 months; OAT, 38.3 months; ACI
1, 19.0 months; ACI-2, 26.7 months). The mean increase in functional outcome
score was 23 for MFx, 19 for OAT, 20 for ACI-1, and 35 for ACI-2. The change in
functional outcome score was significantly greater for ACI-2 when compared with
all other treatments (P < .0001). The cost-per-point change in functional outcome
score was $200.59 for MFx, $313.84 for OAT, and $536.59 for ACI-1. CONCLUSION:
MFx, OAT, ACI-1, and ACI-2 are effective surgical procedures for the treatment of
cartilage defects in the knee. All 4 treatments led to an increase in functional
outcome scores postoperatively with a short-term follow-up. ACI-2 had a
statistically greater improvement in functional outcome scores as compared with
the other 3 procedures. MFx was found to be the most cost-effective treatment
option and ACI-1 the least cost-effective.
PMID- 28516107
TI - Building a central nervous system: The neural stem cell lineage revealed.
AB - Neural stem cells (NSCs) are a multipotent, self-renewing source of
undifferentiated cells in the periventricular region of the mammalian central
nervous system (CNS). Since their original discovery 25 years ago, much has been
learned about their development, persistence, localization, properties and
potential. Herein we discuss the current state of knowledge pertaining to neural
stem cells with a focus on the lineage relationship between two NSC populations
along the neuraxis and their regionally distinct niches in the CNS.
PMID- 28516109
TI - Serum-Derived Bovine Immunoglobulin as Novel Adjunct in Complicated Clostridium
difficile Colitis Treatment.
AB - Clostridium difficile infection (CDI) is a well-known complication of antibiotic
therapy. It is associated with significant morbidity, mortality, and cost in the
hospital setting. The main symptoms include watery diarrhea, abdominal pain, and
distension, but CDI can also present as toxic megacolon, bowel perforation with
peritonitis, sepsis and renal failure. Therapy includes metronidazole and oral
vancomycin, with rectal vancomycin and fecal transplant reserved for more
complicated cases. Adjunctive treatments such as probiotics have been tried with
mixed results. We present a patient with complicated CDI treated with adjuvant
serum-derived bovine immunoglobulin, a novel approach in this context.
PMID- 28516110
TI - Large Bowel Obstruction following Endoscopic Spray Cryotherapy for Palliation of
Rectal Cancer Bleeding.
AB - We report a unique case of a 79-year-old woman with metastatic rectal cancer who
developed bowel obstruction following endoscopic cryotherapy with liquid nitrogen
for palliation of bleeding in the rectum. She developed abdominal distention and
pain following the procedure. Computed tomography of the abdomen revealed a
paraumbilical hernia containing a segment of transverse colon resulting in
partial bowel obstruction. It appears that the recurrent freeze-thaw cycles with
poor decompression of the colon despite active venting suction during cryotherapy
may have resulted in bowel distention and collapse, causing conformational
changes resulting in partial bowel obstruction due to a paraumbilical hernia.
PMID- 28516108
TI - What is CAR doing in the middle of the adult neurogenic road?
AB - The molecular and cellular basis of adult neurogenesis has attracted considerable
attention for fundamental and clinical applications because neural stem cells and
newborn neurons may, one day, be harnessed to replace neurons and allow cognitive
improvement in the diseased brain. In rodents, neural progenitors are located in
the dentate gyrus and the sub/periventricular zone. In the dentate gyrus the
generation of newborn neurons is associated with plasticity, including regulation
of memory. The role of subventricular zone neural precursors that migrate to the
olfactory bulb is less characterized. Identifying factors that impact neural stem
cell proliferation, migration and differentiation is therefore sine qua non
before we can harness their potential. Here, we expand upon our recent results
showing that CAR, the coxsackievirus and adenovirus receptor, is among the
developing list of key players when it comes to the complex process of
integrating newborn neurons into existing circuits in the mature brain.
PMID- 28516111
TI - Transhiatal Herniation of the Pancreas: A Rare Cause of Acute Pancreatitis.
AB - Transhiatal herniation of the pancreas is rare. Acute pancreatitis secondary to
this phenomenon is particularly unusual. A 102-year-old woman presented with 1
day of severe chest pain, vomiting, dyspnea, and diaphoresis. Serum lipase was
elevated, and computed tomography angiogram of the chest and magnetic resonance
cholangiopancreatography revealed a hiatal hernia containing the pancreas, with
associated findings of pancreatitis. Pancreatitis in this setting may be due to
repetitive trauma or ischemia from sliding, intermittent folding of the
pancreatic duct, or pancreatic incarceration. Mild cases can be managed
supportively, with surgery being reserved for severe cases or for younger
patients with low surgical risk.
PMID- 28516112
TI - Hemorrhagic Cystitis in a Liver Transplant Recipient Secondary to BK Virus.
AB - The association between BK virus infection and hemorrhagic cystitis (HC) in
hematopoietic stem cell transplant (HSCT) recipients is well established.
However, BK virus-associated HC has not been described in liver transplant (LT)
recipients. We present a case of BK virus-associated HC in a LT recipient. Our
patient presented with worsening liver function tests 2 years after
transplantation and was found to have acute cellular rejection. He was treated
with increased immunosuppression and subsequently developed hematuria. He was
eventually diagnosed with BK virus-associated HC.
PMID- 28516113
TI - Pit Assay to Measure the Bone Resorptive Activity of Bone Marrow-derived
Osteoclasts.
AB - Although it is possible to use a tartrate-resistant acid phosphatase (TRAP) stain
to assist in identifying osteoclasts, a separate method is needed to determine
the bone resorption activity of osteoclasts. Since osteoclasts leave "pits" after
bone matrix resorption (Charles et al., 2014), it is possible to stain pits as a
method of measuring osteoclast bone resorption activity. The pit assay protocol
enables researchers to stain bony slices that were co-cultured with osteoclasts
with toluidine blue in order to allow the visualization, capture, and analysis of
osteoclast resorptive activity based on the number, size and depth of pits (Zhou
et al., 2015). The pit assay protocol is separated into three sequential stages:
Preparation of bone slices (1); preparation of osteoclast precursors (Ross et
al., 2006; Teitelbaum et al., 2000) (2), and bone resorption pit assay (3).
PMID- 28516114
TI - Measurement of mRNA Decay in Mouse Embryonic Fibroblasts.
AB - mRNA stability control is a critical step in the post-transcriptional regulation
of gene expression. Actinomycin D, an antibiotic initially used as an anti-cancer
drug, has turned out to be a convenient tool for studying the turnover rates of
transcripts in cells, due to its inhibition of mRNA synthesis. Here, we describe
a protocol for the measurement of mRNA decay after adding actinomycin D into the
medium of stable fibroblast cell lines derived from wild-type and tristetraprolin
(TTP)-deficient mouse embryonic fibroblast (MEF) cultures, as well as a protocol
for determining the relative transcript abundance using semi-quantitative real
time RT-PCR. Northern blotting or NanoString n-Counter are alternative methods to
measure mRNA abundance, which is quantified using a phosphorimager in the former
case. This protocol is suitable for studying primary cultured cells and stable
cell lines derived from transgenic mice and their respective controls, and
provides for direct comparisons of mRNA decay rates in otherwise identical cells
with and without the gene of interest.
PMID- 28516115
TI - A Modified Chromogenic Assay for Determination of the Ratio of Free Intracellular
NAD+/NADH in Streptococcus mutans.
AB - Nicotinamide adenine dinucleotide is a coenzyme present in all kingdoms of life
and exists in two forms: oxidized (NAD+) and reduced (NADH). NAD(H) is involved
in a multitude of essential metabolic redox reactions, providing oxidizing or
reducing equivalents. The ratio of free intracellular NAD+/NADH is fundamentally
important in the maintenance of cellular redox homeostasis (Ying, 2008). Various
chromogenic cycling assays have been used to determine the ratio of NAD+/NADH in
both bacterial and mammalian cells for more than forty years (Bernofsky and Swan,
1973; Nisselbaum and Green, 1969). Here, we describe in detail an assay to
determine the ratio of free intracellular NAD+ to NADH in Streptococcus mutans.
This cycling assay is a modified version of the protocol first described by
Bernofsky and Swan (Bernofsky and Swan, 1973), using the extraction buffer
described by Frezza et al. (2011), followed by the reduced MTT precipitation
described by Gibbon and Larher (Gibon and Larher, 1997). As depicted in Figure 1,
alcohol dehydrogenase is used to drive a series of redox reactions utilizing
exogenously added ethanol and NAD+ from sample extracts as initial substrates,
phenazine ethosulfate (PES) as an electron carrier, and thiazolyl blue
tetrazolium bromide (MTT) as a terminal electron acceptor. 6 M NaCl is used to
stop the reaction. The reduced MTT (formazan dye) is purple in color and can be
quantified by measuring absorbance at 570 nm. This protocol is divided into three
steps: A. Preparation of cell pellets of S. mutans; B. Preparation of
deproteinated cell extracts containing NADtotal or NADH; C. NAD+/NADH cycling
assay. This method has proven robust in measuring the NAD+/NADH ratio in S.
mutans under a variety of conditions, and should be applicable to other Gram
positive bacteria.
PMID- 28516116
TI - ASC-particle-induced Peritonitis.
AB - In response to pathogen infection and tissue damage, inflammasome sensors such as
NLRP3 and AIM2 are activated, which triggers PYRIN domain (PYD)-mediated ASC
nucleation, followed by self-perpetuating ASC polymerization, which ultimately
culminates in caspase-1 activation, interleukin (IL)-1beta and IL-18 processing
and release and pyroptosis (Ratsimandresy et al., 2013; Cai et al., 2014).
Inflammasomes release not only cytokines, but also the polymeric ASC danger
particles (pASC) by pyroptosis, which perpetuate and propagate inflammasome
responses to bystander cells to engage cell intrinsic ASC and caspase-1 (Baroja
Mazo et al., 2014; Franklin et al., 2014). In this protocol we describe
intraperitoneal injection of polymeric ASC particles as a danger signal and
measure neutrophil infiltration and levels of the pro-inflammatory cytokine IL
1beta by ELISA in the peritoneal lavage (de Almeida et al., 2015).
PMID- 28516117
TI - Reconstruction of the Mouse Inflammasome System in HEK293T Cells.
AB - The NLRP3 (NLR family, Pyrin domain containing 3) inflammasome is a multiprotein
complex comprised of NLRP3, pro-caspase-1, the adaptor protein apoptosis
associated speck-like protein containing a CARD (ASC), and the protein kinase
NIMA related kinase 7 (NEK7) (Shi et al., 2016; He et al., 2016; Schmid-Burgk et
al., 2016). When cells are exposed to microbes and/or danger signals, the
inflammasome assembles and serves as a platform for the activation of caspase-1.
Caspase-1 activation promotes the processing and secretion of the pro
inflammatory cytokines interleukin-1beta (IL-1beta), IL-18, and IL-33 as well as
pyroptosis induction (Gross et al., 2011; Arend et al., 2008), which elicit
inflammatory responses. Here, we describe how to co-transfect the NLRP3
inflammasome components into HEK293T cells, which enables inflammasome activation
and the production of IL-1beta upon stimulation with nigericin.
PMID- 28516118
TI - Quantitative Measurements of HIV-1 and Dextran Capture by Human Monocyte-derived
Dendritic Cells (MDDCs).
AB - : The aim of this protocol is to describe how to measure and quantify the amount
of HIV-1 particles and dextran molecules internalized in human monocyte derived
dendritic cells (MDDCs), using three different techniques: flow cytometry,
quantitative PCR and confocal microscopy. BACKGROUND: This protocol was developed
in order to assess the changes of HIV-1 internalization upon disruption of actin
nucleation in human monocyte derived dendritic cells. Following a shRNA screen to
identify genes important for HIV-1 transfer from dendritic cells to T cells, we
observed that a disruption of actin nucleation leads to a switch from actin rich
dendrites to blebs, due to an excess of actomyosin contraction. As a consequence,
a decrease of HIV-1 transfer and an increase of HIV-1 internalization due to bleb
retraction-driven macropinocytosis were observed. We concluded that effectors of
actin nucleation and stabilization were key to maintain HIV-1 on actin-rich
dendrites and to limit its endocytosis, for efficient transfer to T lymphocytes
(Menager and Littman, 2016).
PMID- 28516119
TI - Affinity Pulldown of Biotinylated RNA for Detection of Protein-RNA Complexes.
AB - RNA-binding proteins (RBPs) have recently emerged as crucial players in the
regulation of gene expression. The interactions of RBPs with target mRNAs control
the levels of gene products by altering different regulatory steps, including pre
mRNA splicing and maturation, nuclear mRNA export, and mRNA stability and
translation (Glisovic et al., 2008). There are several methodologies available
today to identify RNAs bound to specific RBPs; some detect only recombinant
molecules in vitro, others detect recombinant and endogenous molecules, while
others detect only endogenous molecules. Examples include systematic evolution of
ligands by exponential enrichment (SELEX), biotinylated RNA pulldown assay, RNA
immunoprecipitation (RIP) assay, electrophoretic mobility shift assay (EMSA), RNA
footprinting analysis, and various UV crosslinking and immunoprecipitation (CLIP)
methods such as CLIP, PAR-CLIP, and iCLIP (Popova et al., 2015). Here, we
describe a simple and informative method to study and identify the RNA region of
interaction between an RBP and its target transcript (Panda et al., 2014 and
2016). Its reproducibility and ease of use make this protocol a fast and useful
method to identify interactions between RBPs and specific RNAs.
PMID- 28516120
TI - Abeta Extraction from Murine Brain Homogenates.
AB - This protocol details beta-amyloid (Abeta) extraction from transgenic murine
brain homogenates. Specifically, mechanical homogenization of brain tissue and
sequential extraction of both soluble and insoluble proteins are detailed. DEA
extracts soluble proteins, such as Abeta isoforms and APP. Formic acid enables
extraction of insoluble protein aggregates, such as Abeta isoforms associated
with plaques. This procedure produces soluble and insoluble extracts that are
amenable to analysis of Abeta species via western blotting and/or enzyme-linked
immunosorbent assays (ELISAs), and these results help assess amyloidogenic burden
in animals.
PMID- 28516121
TI - Simultaneous Intranasal/Intravascular Antibody Labeling of CD4+ T Cells in Mouse
Lungs.
AB - CD4+ T cell responses have been shown to be protective in many respiratory virus
infections. In the respiratory tract, CD4+ T cells include cells in the airway
and parenchyma and cells adhering to the pulmonary vasculature. Here we discuss
in detail the methods that are useful for characterizing CD4+ T cells in
different anatomic locations in mouse lungs.
PMID- 28516123
TI - Polysome Fractionation to Analyze mRNA Distribution Profiles.
AB - Eukaryotic cells adapt to changes in external or internal signals by precisely
modulating the expression of specific gene products. The expression of protein
coding genes is controlled at the transcriptional and post-transcriptional
levels. Among the latter steps, the regulation of translation is particularly
important in cellular processes that require rapid changes in protein expression
patterns. The translational efficiency of mRNAs is altered by RNA-binding
proteins (RBPs) and noncoding (nc)RNAs such as microRNAs (Panda et al., 2014a and
2014b; Abdelmohsen et al., 2014). The impact of factors that regulate selective
mRNA translation is a critical question in RNA biology. Polyribosome (polysome)
fractionation analysis is a powerful method to assess the association of
ribosomes with a given mRNA. It provides valuable information about the
translational status of that mRNA, depending on the number of ribosomes with
which they are associated, and identifies mRNAs that are not translated (Panda et
al., 2016). mRNAs associated with many ribosomes form large polysomes that are
predicted to be actively translated, while mRNAs associated with few or no
ribosomes are expected to be translated poorly if at all. In sum, polysome
fractionation analysis allows the direct determination of translation
efficiencies at the level of the whole transcriptome as well as individual mRNAs.
PMID- 28516122
TI - Two-electrode Voltage-clamp Recordings in Xenopus laevis Oocytes: Reconstitution
of Abscisic Acid Activation of SLAC1 Anion Channel via PYL9 ABA Receptor.
AB - Two-Electrode Voltage-Clamp (TEVC) recording in Xenopus laevis oocytes provides a
powerful method to investigate the functions and regulation of ion channel
proteins. This approach provides a well-known tool to characterize ion channels
or transporters expressed in Xenopus laevis oocytes. The plasma membrane of the
oocyte is impaled by two microelectrodes, one for voltage sensing and the other
one for current injection. Here we list a protocol that allows robust
reconstitution of multi-component signaling pathways. This protocol has been used
to study plant ion channels, including the SLAC1 channel (SLOW ANION CHANNEL
ASSOCIATED 1), in particular SLAC1 activation by either the protein kinase OST1
(OPEN STOMATA 1), Ca2+-dependent protein kinases (CPKs) or the GHR1 (GUARD CELL
HYDROGEN PEROXIDE-RESISTANT 1) transmembrane receptor-like protein. Data are
presented showing reconstitution of abscisic acid activation of the SLAC1 anion
channel by the 'monomeric' ABA (abscisic acid) receptor RCAR1/PYL9 (PYRABACT
INRESISTANCE1 [PYR1]/PYR1-LIKE [PYL]/REGULATORYCOMPONENTS OF ABA RECEPTORS
[RCAR]) by co-expressing four components of the abscisic acid signaling core.
This protocol is also suitable for studying other ion channel functions and
regulation mechanisms, as well as transporter proteins.
PMID- 28516124
TI - Bioinformatic Analysis for Profiling Drug-induced Chromatin Modification
Landscapes in Mouse Brain Using ChlP-seq Data.
AB - Chromatin immunoprecipitation followed by massively parallel sequencing (ChIP
seq) is a powerful technology to profile genome-wide chromatin modification
patterns and is increasingly being used to study the molecular mechanisms of
brain diseases such as drug addiction. This protocol discusses the typical
procedures involved in ChIP-seq data generation, bioinformatic analysis, and
interpretation of results, using a chronic cocaine treatment study as a template.
We describe an experimental design that induces significant chromatin
modifications in mouse brain, and the use of ChIP-seq to derive novel information
about the chromatin regulatory mechanisms involved. We describe the bioinformatic
methods used to preprocess the sequencing data, generate global enrichment
profiles for specific histone modifications, identify enriched genomic loci, find
differential modification sites, and perform functional analyses. These ChIP-seq
analyses provide many details into the chromatin changes that are induced in
brain by chronic exposure to cocaine, and generates an invaluable source of
information to understand the molecular mechanisms underlying drug addiction. Our
protocol provides a standardized procedure for data analysis and can serve as a
starting point for any other ChIP-seq projects.
PMID- 28516125
TI - Determination of the in vitro Sporulation Frequency of Clostridium difficile.
AB - The anaerobic, gastrointestinal pathogen, Clostridium difficile, persists within
the environment and spreads from host-to-host via its infectious form, the spore.
To effectively study spore formation, the physical differentiation of vegetative
cells from spores is required to determine the proportion of spores within a
population of C. difficile. This protocol describes a method to accurately
enumerate both viable vegetative cells and spores separately and subsequently
calculate a sporulation frequency of a mixed C. difficile population from various
in vitro growth conditions (Edwards et al., 2016b).
PMID- 28516126
TI - An HPLC-based Method to Quantify Coronatine Production by Bacteria.
AB - Coronatine is a polyketide phytotoxin produced by several pathovars of the plant
pathogenic bacterium Pseudomonas syringae. It is one of the most important
virulence factors determining the success of bacterial pathogenesis in the plant
at both epiphytic and endophytic stages of the disease cycle. This protocol
describes an optimized procedure to culture bacterial cells for coronatine
production and to quantify the amount of coronatine secreted in the culture
medium using an HPLC-based method.
PMID- 28516127
TI - A Pilot Study for Linking Adolescent Patients to an Interactive Tobacco
Prevention Program.
AB - CONTEXT: The American Academy of Pediatrics and professional guidelines recommend
intervening with adolescents about avoiding tobacco use in the health-care
setting. Barriers in the clinical setting limit consistent provision of this
critical service. OBJECTIVES: This pilot study compared 2 approaches for
referring adolescents to an evidence-based tobacco prevention and cessation
program in the outpatient setting. Secondary aims assessed tobacco use,
knowledge, and program evaluation. DESIGN SETTING AND PARTICIPANTS: The study
setting was a medical and dental clinic. Participants aged 13 to 18 received
tobacco advice and instructions to work through "A Smoking Prevention Interactive
Experience." The program addresses health concerns of adolescents about tobacco
use and is founded on behavioral change theories. The link to access it is
featured on the website of the National Cancer Institute's Research-Tested
Interventions. Participants (N = 197) were randomized to 1 of 2 approaches (ie, a
program link via e-mail or referral by a printed card). RESULTS: The program was
accessed by 57% (112 of 197) of participants. Both referral approaches were
equally effective. Non-Hispanics were twice as likely to access the program as
Hispanics (adjusted odds ratio = 2.1, 95% confidence interval = 1.2-3.8, P <
.05). Over 95% of participants identified themselves as nonusers of tobacco and
evaluated the program as beneficial in increasing knowledge and motivation to
remain tobacco-free. CONCLUSION: Linking adolescent patients to an evidence-based
tobacco prevention/cessation program at a community health clinic was highly
promising and feasible. We present conclusions for future research.
PMID- 28516128
TI - Parental Experiences of Raising a Child With Medium Chain Acyl-CoA Dehydrogenase
Deficiency.
AB - Newborn screening enabling early diagnosis of medium chain acyl-CoA dehydrogenase
deficiency (MCADD) has dramatically improved health outcomes in children with
MCADD. Achieving those outcomes depends on effective management by parents.
Understanding parental management strategies and associated anxieties and
concerns is needed to inform provision of appropriate care and support.
Semistructured interviews were conducted with a purposive sample of parents of
children aged 2 to 12 years. Thematic analysis identified two main themes.
Managing dietary intake examined how parents managed day-to-day dietary intake to
ensure adequate intake and protection of safe fasting intervals. Managing and
preventing illness events explored parental experiences of managing illness
events and their approach to preventing these events. Management strategies were
characterized by caution and vigilance and influenced by a lack of confidence in
others to manage the condition. The study identifies the need for increased
awareness of the condition, particularly in relation to emergency treatment.
PMID- 28516129
TI - Enhanced Recovery After Colorectal Surgery (ERAS) in Elderly Patients Is Feasible
and Achieves Similar Results as in Younger Patients.
AB - Aim: Enhanced recovery after surgery (ERAS) is a multimodal approach that aims to
optimize perioperative treatment. Whether elderly patients receiving colorectal
surgery can adhere to and benefit from an ERAS approach is uncertain. The aim of
this study was to compare patients in different age groups participating in an
ERAS program. Method: In this substudy of a randomized controlled trial, we
analyzed the interventional ERAS arm of adult patients eligible for laparoscopic
or open colorectal resection with regard to the importance of age. Patients were
divided into three groups based on age: <=65 years (n = 79), 66-79 years (n =
56), and >=80 years (n = 19). The primary end point was total postoperative
hospital stay (THS). Secondary end points were postoperative hospital stay,
postoperative complications, postoperative C-reactive protein levels, readmission
rate, mortality, and patient adherence to the different ERAS elements. All
parameters and measuring the adherence to the ERAS protocol were recorded before
surgery, on the day of the operation, and daily until discharge. Results: There
were no significant differences in length of THS between age groups (<=65 years,
median 5 [range 2-47] days; 66-79 years, median 5.5 [range 2-36] days; >=80
years, median 7 [range 3-50] days; p = .53). All secondary outcomes were similar
between age groups. Patient adherence to the ERAS protocol was as good in the
elderly as it was in the younger patients. Conclusion: Elderly patients adhered
to and benefited from an ERAS program, similar to their younger counterparts.
PMID- 28516130
TI - Nutritional Status and Body Composition of Independently Living Older Adults in a
Snowy Region of Japan.
AB - Lifestyle diseases, which are associated with nutrition, account for 30% of
elderly requiring long-term care. To increase health expectancy among Japan's
rapidly aging population, we investigated the nutritional status and body
composition of elderly adults living in a region subject to heavy snowfall, to
identify pertinent health indicators. The dietary habits of 288 local residents
aged >=50 years were analyzed using body composition and a brief-type self
administered diet history questionnaire. Body mass index of all residents was
normal. Basal metabolic rate (BMR) and muscle mass were reduced in the older
group. Dietary habits did not differ with age among men, but older women had
significantly higher dietary intake. BMR and muscle mass declined with age, even
when dietary intake was sustained. Despite sufficient dietary intake,
independently living older adults demonstrate less efficient use of food with
age. Interventions to reduce excessive sodium and protein intake are required.
PMID- 28516131
TI - The Cardiac Sympathetic Nerve Activity in the Elderly Is Attenuated in the Right
Lateral Decubitus Position.
AB - Objectives: The aim of this study was to evaluate the effect of the supine, left
lateral decubitus, and right lateral decubitus positions on autonomic nervous
activity in elderly adults by using spectral analysis of heart rate variability
(HRV). Method: Forty-five adults aged 73.6 +/- 5.7 years were enrolled. After
lying in the supine position, all participants moved to the lateral decubitus
positions in a random order and maintained the positions for 10 min, while
electrocardiographic data were recorded to measure HRV. Results: The lowest heart
rate continued for 10 min when participants were in the left lateral decubitus
position compared with the other two positions (p < .001), while the HRV indexes
remained unchanged. The low-frequency HRV to high-frequency HRV ratio (LF/HF) for
the right lateral decubitus position was significantly lower than that for the
other positions. Discussion: The right lateral decubitus position may attenuate
sympathetic nerve activity in elderly adults.
PMID- 28516133
TI - Transcatheter arterial chemoembolization of hepatocellular carcinoma in patients
with celiac axis occlusion using pancreaticoduodenal arcade as a challenging
alternative route.
AB - INTRODUCTION: Celiac axis occlusion is a challenging condition when
catheterization of the hepatic artery is required for chemoembolization of
hepatocellular carcinoma (HCC). As a result, the hepatic artery has to be
catheterized through the pancreaticoduodenal arcades (PDA) and the gastroduodenal
artery (GDA) from the superior mesenteric artery (SMA) which is a tortuous course
with acute angles and small caliber branches. OBJECTIVE: To assess new techniques
for facilitating catheterization of the tortuous PDA and the GDA to reach the
proper hepatic artery (PHA) and tumor-feeding branches in patients with celiac
axis occlusion undergoing chemoembolization of HCC. METHODS AND MATERIALS: The
study included eleven patients all admitted to do transcatheter arterial
chemoembolization (TACE) for treatment of unresectable HCC. During angiography
occlusion of the celiac axis was diagnosed and hypertrophied PDA and GDA was
noted in SMA angiography. Catheterization of the PDA was performed by preshaping
of the micro-guide wire into a wide curve. Catheterization of the PHA was a
challenge and was achieved by reshaping of the micro-guide wire or by looping
technique. TACE was done after super selective catheterization of the tumor
feeding artery using a mixture of 50 mg of adriamycin, 7cc of lipiodol and
gelfoam. RESULTS: In the eleven patients with celiac artery occlusion, DSA showed
complete celiac axis occlusion in all patients. Collateral arteries supplying the
liver were readily evident via PDA and GDA from SMA. Successful catheterization
of the PHA was achieved in all patients. Chemoembolization was performed to all
patients after super selective catheterization of the feeding artery. Follow-up
triphasic CT was performed in all patients, 9 patients showed good lipiodol
trapping with no residual tumor enhancement. Two patients required another
session of TACE. CONCLUSION: Chemoembolization of HCC through the PDA and the GDA
using micro-guide wire preshaping technique and the microcatheter looping
technique in patients with celiac axis occlusion is a challenging but effective
treatment for HCC.
PMID- 28516132
TI - Life-Threatening Hypercalcemia During Prodrome of Pneumocystis jiroveci Pneumonia
in an Immunocompetent Infant.
AB - Severe hypercalcemia in infants is usually attributed to genetic etiologies and
less commonly to acquired ones. An 8-week-old girl presented with failure to
thrive, mild respiratory distress, and life-threatening hypercalcemia (23.5
mg/dL). Serum 1,25(OH)2-vitamin D (1,25(OH)2-D) level was elevated and
parathyroid hormone undetectable. Evaluation for genetic mutations and malignant
etiologies of hypercalcemia was negative. Treatment with intravenous hydration,
loop diuretic, and calcitonin failed to correct the hypercalcemia, which was
subsequently controlled with bisphosphonate therapy. Due to progressive
respiratory deterioration, a bronchopulmonary lavage was done on day 17 of her
hospitalization disclosing Pneumocystis jiroveci infection. The subsequent
immunological investigation showed no abnormalities. She was treated with
trimethoprim/sulfamethoxazole resulting in gradual clearing of her lungs and
normalization of serum 1,25(OH)2-D level. A year later, she remains healthy with
normal biochemical parameters of mineral metabolism. We conclude that in a child
with hypercalcemia with suppressed parathyroid hormone and elevated 1,25(OH)2-D,
once the genetic etiology for elevated 1,25(OH)2-D and malignancy are ruled out,
one should investigate closely for a chronic granulomatous disease. Among the
latter Pneumocystis jiroveci pneumonia infection should be considered even in an
immunocompetent child.
PMID- 28516134
TI - Data on metals biomonitoring in the body of schoolchildren in the vicinity of a
heavily industrialized site.
AB - This data is obtained from analyzing the concentration of metals include Al, Co,
Cr, Cu, Fe, Mo, Pb, and Zn in the urine of schoolchildren in Asalouyeh city in
vicinity to a heavily industrialized site and comparison with a reference city.
The significance of sex groups on urine metal level was evaluated through this
data. The urinary content of metals was measured by inductively coupled plasma
atomic emission spectroscopy (ICP-OES). Statistical analyze of data were done by
Mann-Whitney test. The herein presented date could beneficial for health
assessment of gas and petrochemical companies.
PMID- 28516135
TI - Data for the synthesis of resorcinol-formaldehyde aerogels in acidic and basic
media.
AB - The aim of this research is to synthesise carbon aerogels and to compare the
differences in their textural, morphological and chemical properties when
synthesised in basic and acidic media, and with two different types of
pretreatment carbonization and activation with CO2. Four samples are prepared and
characterised using TGA-DTA, SEM, DRX, isotherm determination of N2 adsorption
desorption at -196 degrees C and immersion calorimetry. The data for pore
distribution are reported using non-local density functional theory and quenched
solid density functional theory. Finally, with the immersion calorimetry data,
the consistency between the results using this technique and those obtained using
the nitrogen isotherms is analysed.
PMID- 28516136
TI - Primers and probe design and precision assessment of the real time RT-PCR assay
in Coxsackievirus A10 and enterovirus detection.
AB - This data article contains data related to the research article entitled "Rapid
detection of enterovirus and Coxsackievirus A10 by a TaqMan based duplex one-step
real time RT-PCR assay" (Chen at al., 2017) [1]. Primers and probe sequence
design are among the most critical factors in real-time polymerase chain reaction
(PCR) assay optimization. Linearity, sensitivity, specificity and precision are
the crucial criteria which are used to evaluate the performance of a new method.
This data article report the primers and probe design and precision assessment of
the new assay. VP1 gene of Coxsackievirus A10 (CV-A10) and 5'-NCR of different
enterovirus (EV) serotypes were retrieved from GenBank database and aligned. The
intra- and inter-assay variation were assessed using high, medium and low
concentration of control plasmid DNA and viral RNA samples.
PMID- 28516137
TI - A curated dataset of complete Enterobacteriaceae plasmids compiled from the NCBI
nucleotide database.
AB - Thousands of plasmid sequences are now publicly available in the NCBI nucleotide
database, but they are not reliably annotated to distinguish complete plasmids
from plasmid fragments, such as gene or contig sequences; therefore, retrieving
complete plasmids for downstream analyses is challenging. Here we present a
curated dataset of complete bacterial plasmids from the clinically relevant
Enterobacteriaceae family. The dataset was compiled from the NCBI nucleotide
database using curation steps designed to exclude incomplete plasmid sequences,
and chromosomal sequences misannotated as plasmids. Over 2000 complete plasmid
sequences are included in the curated plasmid dataset. Protein sequences produced
from translating each complete plasmid nucleotide sequence in all 6 frames are
also provided. Further analysis and discussion of the dataset is presented in an
accompanying research article: "Ordering the mob: insights into replicon and MOB
typing..." (Orlek et al., 2017) [1]. The curated plasmid sequences are publicly
available in the Figshare repository.
PMID- 28516138
TI - Data on metabolic-dependent antioxidant response in the cardiovascular tissues of
living zebrafish under stress conditions.
AB - In this article we used transgenic zebrafish lines that express compartment
specific isoforms of the roGFP2-Orp1 and Grx1-roGFP2 biosensors, described in
Panieri et al (2017) [1], to test the contribute of the pentose phosphate pathway
and of the glutathione biosynthesis in the antioxidant capacity of myocardial and
endothelial cells in vivo. The transgenic zebrafish embryos were subdued to
metabolic inhibition and subsequently challenged with H2O2 or the redox-cycling
agent menadione to respectively mimic acute or chronic oxidative stress. Confocal
time-lapse recordings were performed to follow the compartmentalized H2O2 and
EGSH changes in the cardiovascular tissues of zebrafish embryos at 48 h post
fertilization. After sequential excitation at 405 nm and 488 nm the emission was
collected between 500-520 nm every 2 min for an overall duration of 60 min. The
405/488 nm ratio was normalized to the initial value obtained before oxidants
addition and plotted over time. The analysis and the interpretation of the data
can be found in the associated article [1].
PMID- 28516139
TI - Dataset of two experiments of the application of gamified peer assessment model
into online learning environment MeuTutor.
AB - In this dataset, we present the collected data of two experiments with the
application of the gamified peer assessment model into online learning
environment MeuTutor to allow the comparison of the obtained results with others
proposed models. MeuTutor is an intelligent tutoring system aims to monitor the
learning of the students in a personalized way, ensuring quality education and
improving the performance of its members (Tenorio et al., 2016) [1]. The first
experiment evaluated the effectiveness of the peer assessment model through
metrics as final grade (result), time to correct the activities and associated
costs. The second experiment evaluated the gamification influence into peer
assessment model, analyzing metrics as access number (logins), number of
performed activities and number of performed corrections. In this article, we
present in table form for each metric: the raw data of each treatment; the
summarized data; the application results of the normality test Shapiro-Wilk; the
application results of the statistical tests T-Test and/or Wilcoxon. The
presented data in this article are related to the article entitled "A gamified
peer assessment model for on-line learning environments in a competitive context"
(Tenorio et al., 2016) [1].
PMID- 28516140
TI - Comprehensive list of metabolites measured by DI-FTICR mass spectrometry in thyme
plants with contrasting tolerance to drought.
AB - This article contains data related to the main research entitled "Metabolomic
approach reveals the biochemical mechanisms underlying drought stress tolerance
in Thyme" (Moradi et al., 2017) [1]. Two thyme populations with contrasting
drought tolerance were subjected to long term water deficit. Leaf samples
harvested at the end of stress period and bi-phasic extraction carried out to get
polar and non-polar fractions. Extracted samples were analyzed through Direct
Infusion FT-ICR mass spectrometry. Date files comprise of four separate tables
for all the putatively identified metabolites and their intensities in watered
and droughted plants. P-values beside each m/z values indicate significances of
difference between peak intensities of stressed and control conditions.
PMID- 28516141
TI - WST-assay data reveal a pH dependence of the mitochondrial succinate reductase in
osteoblast-like cells.
AB - The data presented in this article are related to the research article entitled
"Increased osteoblast viability at alkaline pH in vitro provides a new
perspective on bone regeneration" (doi: 10.1016/j.bbrep.2017.02.001; (Galow et
al., 2017) [1]). The water soluble tetrazolium (WST) proliferation assay detects
the metabolic activity of the respiratory chain of cultured cells. The assay is
based on changes in the light absorbance resulting from the metabolism of WST-1
into formazane by mitochondrial succinate reductase. We present data of three
different tests that were carried out to check whether WST assay readouts are pH
dependent. In a first test, a possible pH effect on the photometric measurements,
for example by shifting the absorbance spectrum of the pH indicator of the cell
culture medium, was excluded. Because the second test revealed a significant pH
dependence of the activity of the mitochondrial succinate reductase, a third long
term test was conducted to analyze possible changes of the pH dependence over
time. The higher absorbance per one million cells at alkaline pH, which was
approximately four-fold at pH 8.4 compared to the pH-7.4 reference on day one
decayed gradually, with the pH-differences equilibrating over six days.
PMID- 28516142
TI - Survey data on factors affecting negotiation of professional fees between Estate
Valuers and their clients when the mortgage is financed by bank loan: A case
study of mortgage valuations in Ikeja, Lagos State, Nigeria.
AB - In this article, two sets of questionnaires were administered to professionals
and clients (commercial banks) on their willingness to negotiate the professional
fees charged by the Estate Valuers assuming that the mortgage in valuation was
financed by bank loan. A range of fees options were provided. Other factors such
as the business environment and mortgage valuation can influence the negotiated
fees when the data obtained from the survey data is analyzed.
PMID- 28516143
TI - Change-point analysis data of neonatal diffusion tensor MRI in preterm and term
born infants.
AB - The data presented in this article are related to the research article entitled
"Mapping the Critical Gestational Age at Birth that Alters Brain Development in
Preterm-born Infants using Multi-Modal MRI" (Wu et al., 2017) [1]. Brain
immaturity at birth poses critical neurological risks in the preterm-born
infants. We used a novel change-point model to analyze the critical gestational
age at birth (GAB) that could affect postnatal development, based on diffusion
tensor MRI (DTI) acquired from 43 preterm and 43 term-born infants in 126 brain
regions. In the corresponding research article, we presented change-point
analysis of fractional anisotropy (FA) and mean diffusivities (MD) measurements
in these infants. In this article, we offered the relative changes of axonal and
radial diffusivities (AD and RD) in relation to the change of FA and FA-based
change-points, and we also provided the AD- and RD-based change-point results.
PMID- 28516144
TI - Geospatial datasets in support of high-resolution spatial assessment of
population vulnerability to climate change in Nepal.
AB - We present a geographic information system (GIS) dataset with a nominal spatial
resolution of one-kilometer composed of grid polygons originally derived and
utilized in a high-resolution climate vulnerability model for Nepal. The
different data sets described and shared in this article are processed and
tailored to the specific objectives of our research paper entitled "High
resolution Spatial Assessment of Population Vulnerability to Climate Change in
Nepal" (Mainali and Pricope, In press) [1]. We share these data recognizing that
there is a significant gap in regards to data availability, the spatial patterns
of different biophysical and socioeconomic variables, and the overall population
vulnerability to climatic variability and disasters in Nepal. Individual
variables, as well as the entire set presented in this dataset, can be used to
better understand the spatial pattern of different physical, biological,
climatic, and vulnerability characteristics in Nepal. The datasets presented in
this article are sourced from different national and global databases and have
been statistically treated to meet the needs of the article. The data are in GIS
ready ESRI shapefile file format of one-kilometer grid polygon with various
fields (columns) for each dataset.
PMID- 28516145
TI - Zinc, nickel, and cobalt ions removal from aqueous solution and plating plant
wastewater by modified Aspergillus flavus biomass: A dataset.
AB - The biomass of Aspergillus flavus was modified by calcium chloride to achieve a
bioadsorbent for treating nickel, cobalt, and zinc ions from aqueous solutions.
The information of pH, bioadsorbent dose, contact time, and temperature effect on
the removal efficiency are presented. The data of Freundlich and Langmuir
isotherm and pseudo-first-order and pseudo-second-order kinetic models are also
depicted. The data showed that the maximum bioadsorption capacity of nickel,
cobalt, and zinc ions is 32.26, 31.06 and 27.86 mg/g, respectively. The
suitability of the bioadsorbent in heavy metals removal at field condition was
tested with a real wastewater sample collected from a plating plant in the final
part of this dataset. Based on the findings, the bioadsorbent was shown to be an
affordable alternative for the removal of metals in the wastewater.
PMID- 28516146
TI - Interactive effects of gallic/ferulic/caffeic acids and anthocyanins on pigment
thermal stabilities.
AB - The data presented in this article are related to the research article entitled
"The effects of gallic/ferulic/caffeic acids on colour intensification and
anthocyanin stability" (Qian et al., 2017) [1]. This paper described preparation
and isolation of anthocyanins from purple sweet potatoes (PSP) and the time
course of anthocyanin profiles treated with gallic, ferulic, or caffeic acids at
95 degrees C. The color appearance of PSPanthocyanins alone, or with gallic,
ferulic, or caffeic acids was described after the 15 h of thermal treatment. The
high resolution mass spectrographs of PSP anthocyanins were determined using UPLC
ESI-HRMS. The spatial interaction of peonidin 3-O-(2-O-beta-D-glucopyranocyl-beta
D-glucopyranoide)-5-O-beta-D-glucopyranoside and gallic/ferulic/caffeic acids was
illustrated by molecular dynamic simulation.
PMID- 28516147
TI - Buyer and seller data from pay what you want and name your own price laboratory
markets.
AB - Pay What You Want (PWYW) and Name Your Own Price (NYOP) are customer-driven
pricing mechanisms that give customers (some) pricing power and that have been
used in service industries with high fixed costs to price discriminate without
setting a reference price. This paper describes buyer and seller data in a series
of induced-value laboratory experiments that compare PWYW and NYOP in monopoly
and competitive situations. Sellers are in a one-shot interaction with buyers.
Sellers using customer-driven pricing mechanisms may exogenously or endogenously
receive additional promotional benefits, for instance through word-of-mouth
effects. The major findings based on the data presented here are reported in the
paper "Delegating Pricing Power to Customers: Pay What You Want or Name Your Own
Price?" (Kramer et al., 2017) [3].
PMID- 28516148
TI - Data of the Modified Somatic Perception Questionnaire (MSPQ) administered to a
sample of immigrants in Genoa (Italy).
AB - This article reports the data of the Modified Somatic Perception Questionnaire
(MSPQ) administered to a sample of 143 immigrants accessing an outpatient clinic
or the general practitioners offices in Genoa (Italy) compared with 186 Italian
patients. For further details and for the interpretation of the data, the reader
is referred to the original publication "Somatic perception, cultural differences
and immigration: results from administration of the Modified Somatic Perception
Questionnaire (MSPQ) to a sample of immigrants" by Bragazzi et al. (2014) [1].
PMID- 28516149
TI - Dataset for acrylate/silica nanoparticles formulations and photocured composites:
Viscosity, filler dispersion and bulk Poisson's ratio.
AB - UV-curable polymer composites are of importance in industry, biomedical
applications, scientific fields, and daily life. Outstanding physical properties
of polymer composites were achieved with nanoparticles as filler, primarily in
enhancing mechanical strength or barrier properties. Structure-property
relationships of the resulting nanocomposites are dictated by the polymer-filler
molecular architecture, i.e. interactions between polymer matrix and filler, and
high surface area to volume ratio of the filler particles. Among monomers,
acrylates and methacrylates attracted wide attention due to their ease of
polymerization and excellent physicochemical and mechanical properties of the
derived polymers. We prepared and photopolymerized two series of formulations
containing hydrophobized silica nanofiller (Aerosil R7200) dispersed in 2
hydroxyethyl acrylate (HEA) or polyethylene glycol diacrylate (PEGDA) monomers.
We compared selected physical properties of the formulations, both before and
after photocuring; specifically the viscosity of formulations and dispersion of
the filler in the polymer matrices. Additionally, we estimated the bulk Poisson's
ratio of the investigated nanocomposites. This article contains data related to
the research article entitled "Nanoscale Young's modulus and surface morphology
in photocurable polyacrylate/nanosilica composites" (Gojzewski et al., 2017) [1].
PMID- 28516150
TI - Proteome dataset of subcutaneous adipose tissue obtained from late pregnant dairy
cows during summer heat stress and winter seasons.
AB - Adipose tissue has a central role in the regulation of metabolism in dairy cows,
and many proteins expressed in this tissue are involved in metabolic responses to
stress (Peinado et al., 2012) [1]. Environmental heat stress is one of the main
stressors limiting production in dairy cattle (Fuquay, 1981; West, 2003) [2],
[3], and there is a complex interaction between heat stress and the transition
period from late pregnancy to onset of lactation, which is manifested in heat
stressed late-gestation cows (Tao and Dahl, 2013) [4]. We recently defined the
proteome of adipose tissue in peripartum dairy cows, identifying 586 proteins of
which 18.9% were differentially abundant in insulin-resistant compared to insulin
sensitive adipose tissue (Zachut, 2015) [5]. That study showed that proteomic
techniques constitute a valuable tool for identifying novel biomarkers in adipose
tissue that are related to metabolic adaptation to stress in dairy cows. The
objective of the present work was to examine the adipose tissue proteome under
thermo-neutral or seasonal heat stress conditions in late pregnant dairy cows. We
have collected subcutaneous adipose tissue biopsies from 10 late pregnant dairy
cows during summer heat stress and from 8 late pregnant dairy cows during winter
season, and identified and quantified 1495 proteins in the adipose tissues. This
dataset of adipose tissue proteome from dairy cows adds novel information on the
variety of proteins that are abundant in this tissue during late pregnancy under
thermo-neutral as well as heat stress conditions. Differential abundance of 107
(7.1%) proteins was found between summer and winter adipose. These results are
discussed in our recent research article (Zachut et al., 2017) [6].
PMID- 28516151
TI - Transport, mechanical and global migration data of multilayer copolyamide
nanocomposite films with different layouts.
AB - Transport, mechanical and global migration data concern multilayer food packaging
films with different layouts, all incorporating a layered silicate/polyamide
nanocomposite as oxygen barrier layer, and a low-density polyethylene (LDPE) as
moisture resistant layer in direct contact with food. The data are related to
"Tuning of co-extrusion processing conditions and film layout to optimize the
performances of PA/PE multilayer nanocomposite films for food packaging" by
Garofalo et al. (2017) [1]. Nanocomposite multilayer films, with different
relative layer thicknesses and clay types, were produced using a laboratory scale
co-extrusion blown-film equipment and were analyzed in terms of transport to
oxygen and water vapor, mechanical properties and overall migration. The results
have shown that all the multilayer hybrid films, based on the copolyamide layer
filled with Cloisite 30B, displayed the most significant oxygen barrier
improvements and the best mechanical properties compared to the unfilled films.
No significant alteration of the overall migration values was observed, as
expectable [2], [3], [4]. The performance improvement was more relevant in the
case of the film with the thinner nanocomposite layer.
PMID- 28516153
TI - Neutrophil to Lymphocyte Ratio (NLR) at the Time of Transurethral Resection of
Bladder Tumor: A Large Retrospective Study and Analysis of Racial Differences.
AB - Introduction: Neutrophil/lymphocyte ratio (NLR) is an indicator of systemic
inflammation and has been proven to be associated with an increased risk of
extravesical disease, decreased cancer specific survival and overall survival in
bladder cancer patients. A large proportion of healthy African Americans have a
WBC count that is persistently lower than the normal range defined for
individuals of European ancestry, this condition has been called "benign ethnic
neutropenia". The purpose of our study was to determine if NLR was different in
patients of African ancestry (AA) vs European ancestry (EA) across different
tumor grades and stages at the time of transurethral resection of bladder
tumor(s) (TURBT). Materials and Methods: The records of consecutive patients who
underwent TURBT were reviewed from the University of Wisconsin and the Atlanta
Veterans' Administration Medical Center (2000-2012). NLR was compared across
tumor stage, tumor grade and ethnicity. Results: 297 consecutive patients met
study criteria. 89% and 86%, were males and of European ancestry (EA)
respectively. NLRs were different across T-stages (Ta-2.5, T1-3.9, T2-3.8; p =
0.001). but not across tumor grades in Ta (LG-2.5 vs HG-3.9, p = 0.57). EA had
higher NLRs than AA (3.4 vs 1.9; p < 0.001). Conclusions: Higher NLRs appear to
be associated with more advanced tumor stage at the time of TURBT. Patients of
African ancestry have lower NLRs across all tumor stages compared to patients of
European ancestry. Ethnicity should be taken into account when interpreting the
NLR in patients with bladder cancer.
PMID- 28516152
TI - CDK4/6 Inhibitors in Cancer Therapy: A Novel Treatement Strategy for Bladder
Cancer.
AB - Patients with metastatic bladder cancer (mBC) treated with cisplatin-based
chemotherapy have a limited median survival of only around 14 months [1]. Despite
over 30 years of basic and clinical research, until recently no therapeutic
options beyond cisplatin-based therapy had entered clinical routine and, at least
in the US, none of the tested agents had been approved for second-line treatment.
This has changed with the advent of immune checkpoint blockade, including
especially PD-1/PD-L1 inhibitors. The high response rates of 24% over a 14.4
month follow up led to the first US Food and Drug Administration (FDA) approval
for a second line therapy for these patients, and it is likely that this marks
the beginning of a new era in the systemic treatment of muscle-invasive bladder
cancer [2-4]. The strong clinical need to improve the medical management of this
disease for those patients, not responding to current therapy has led to an
increased molecular understanding of bladder cancer and has forstered the
development of many potential molecular manipulations and targeted strategies
beyond the new immune-oncologic approaches. Among the molecular alterations
indentified in bladder cancer, cell cycle deregulation appears to be a key driver
of disease progression. Target-directed therapy against CDK4/6 is an emerging
strategy to regain control of cell cycle deregulation. Here, we provide an
overview of the current status of CDK4/6 inhibitors in cancer therapy, their
potential use in mBC and the challenges for their clinical use.
PMID- 28516154
TI - WBC Associates with Readmission Following Cystectomy.
AB - Background: Radical cystectomy is associated with perioperative complication
rates exceeding 50% in some series. Readmission rates are increasingly used as a
surgical quality metric. White blood cell count is a crude surrogate for
physiologic processes which may reflect postoperative complications leading to
readmission. Objective: We assessed the association between final white blood
cell count at discharge and risk of readmission following radical cystectomy.
Methods: Records on 477 patients undergoing radical cystectomy from 2006-2013
were reviewed. Final white blood cell count was defined as the last documented
value during index admission. Univariate analysis was performed using Fisher's
exact, Wilcoxon rank sum test, and Spearman's coefficient tests where
appropriate. Multivariable logistic regression models were used to test the
associations between final white blood cell count and readmission. Results: 34%
of patients were readmitted within 90 days of surgery. Amongst this cohort, a
cutoff final white blood cell count of 9000/mm3 was identified, with a
significantly higher proportion of patients with values >9000/mm3 experiencing
readmission than those with values<=9000/mm3 (42% vs 28%, p = 0.004). Other
perioperative variables associated with an increased readmission rate included
initial hospital length of stay<=10 days, and receipt of a continent diversion.
Following adjustment, final white blood cell count >9000/mm3 was associated with
increased risk of readmission (OR 2.09, 95% CI 1.23-3.53, p = 0.006).
Conclusions: Final white blood cell count is associated with hospital readmission
following radical cystectomy. This metric may provide important guidance in
discharge algorithms.
PMID- 28516155
TI - Phase I Clinical Trial of Everolimus Combined with Trimodality Therapy in
Patients with Muscle-Invasive Bladder Cancer.
AB - Background: Local control following trimodality therapy (TMT) for muscle-invasive
bladder cancer (MIBC) requires further optimization. Objective: Evaluating the
biologic endpoint, feasibility, and toxicity of integrating everolimus to TMT in
patients with MIBC. Methods: This was a phase I trial in patients with MIBC who
were not surgical candidates or who refused cystectomy. Following maximal
transurethral tumor resection, patients were treated by radiotherapy (50 Gy/20
fractions), gemcitabine (100 mg/m2/weekly) and escalating doses of everolimus
(2.5-5.0 mg/day). Everolimus was given daily for one month prior to radiation,
during treatment, and one month post-radiation. Toxicity assessment followed the
Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring Criteria.
Biologic endpoint with downregulation of phospho-S6 (pS6) was assessed using
immunohistochemistry. Local response was evaluated with imaging and bladder
biopsy post-therapy. Results: 10 patients were recruited; 8 males, 2 females.
Median age was 78 years (range: 63-85). Four patients entered everolimus 2.5 mg
cohort. Six other patients entered everolimus 5.0 mg cohort. Toxicities were
encountered in 2 patients (Grade I), 6 patients (Grade II), 9 patients (Grade
III) and 1 patient (Grade IV), with some experiencing more than one toxicity.
Most Grade III and IV toxicities were encountered from everolimus alone prior to
combination testing. Trial was terminated early due to toxicity. Interestingly,
6/10 patients (60%) achieved a complete response with negative post-treatment
biopsies. Significant decrease of pS6 was demonstrated post-therapy (p = 0.03).
Conclusions: Although combining everolimus with TMT achieved a biological
endpoint and complete response in a significant number of patients with MIBC and
negative prognostic factors, it was associated with unacceptable increased
toxicity.
PMID- 28516156
TI - Single Arm Phase I/II Study of Everolimus and Intravesical Gemcitabine in
Patients with Primary or Secondary Carcinoma In Situ of the Bladder who failed
Bacillus Calmette Guerin (NCT01259063).
AB - Background: Standard treatment for BCG-refractory urothelial cancer is radical
cystectomy. Identification of active agents is clearly warranted. Objective: To
determine a safe dose of oral everolimus in combination with standard
intravesical gemcitabine and to evaluate the efficacy of this combination.
Methods: Patients with carcinoma in situ refractory to intravesical bacillus
Calmette-Guerin and refusing cystectomy were eligible. Patients in the phase I
part of the trial received one of three dose levels of oral everolimus. Patients
also received a fixed dose of intravesical gemcitabine. Maintenance everolimus
was given for 12 months in patients achieving a complete response confirmed by
cystoscopy and cytology. Patients in phase II received continuous everolimus
administered at 10 mg daily with intravesical gemcitabine followed by everolimus
maintenance for 12 months of total therapy. The enrollment goal for the phase II
was 33 patients. Results: 14 patients were enrolled in phase I of the trial. 23
patients were enrolled in phase II of the trial and 19 were evaluable for primary
and secondary endpoints. Four patients withdrew consent prior to treatment
initiation. Of the 19 patients evaluable for response, 3 (16%, 95% confidence
interval [CI] 3% - 40%) were disease free at 1 yr. The probability of RFS was 20%
(95% CI 5% - 42%) at 12 months. Ten patients out of 19 had grade 3 or greater
toxicity events. Seven withdrew consent or were taken off study. Conclusions:
Many patients withdrew, and enrollment was halted. Continuous oral everolimus
plus intravesical gemcitabine was not well tolerated in this patient population
where the threshold for tolerability is low.
PMID- 28516158
TI - A Management Algorithm for Mitomycin C Induced Cystitis.
AB - Background/Objective: A post-bladder tumor resection dose of MMC can reduce non
invasive papillary (pTa) bladder cancer recurrences by up to 40%; this treatment
is recommended in both the AUA and EUA non-muscle-invasive bladder cancer
guidelines. A common complication of this treatment is eosinophilic cystitis.
Symptoms range from mild urinary frequency and urgency to debilitating pain and
dysuria. Currently, there is no established treatment algorithm for MMC-induced
cystitis. Methods: Members of the Urologic Surgery Quality Collaborative (USQC),
a group composed of over 160 private and academic urologists, met to discuss the
management of patients with cystitis following MMC therapy. They devised a
treatment algorithm based on experiences of urologic oncologists and
neurourologists to aid in the diagnosis and management of MMC-induced cystitis.
Results: The assessment begins with urinalysis and culture, followed by
cystoscopy. For mild symptoms, behavioral therapy, including timed voids, fluid
restriction and Kegel exercises are trialed. If symptoms have not resolved,
treatment with an antihistamine, followed by a combination of anticholinergic and
alpha-blocker medications. For persistent symptoms or severe symptoms at
presentation, a course of prednisone plus antihistamine is prescribed. If
symptoms are improving but have not resolved, this treatment is extended for a
full 4 weeks prior to steroid taper. If symptoms do not improve, any visible
bladder ulcerations are resected intraoperatively followed by an additional
course of prednisone and antihistamine. Intravesical DMSO instillations and intra
ulcer steroid injection can be used as a final effort to treat this condition.
Conclusion: We present the first formal management algorithm with escalating
treatment intensity tailored to patient symptoms.
PMID- 28516157
TI - Survival after Metastasectomy for Metastatic Urothelial Carcinoma: A Systematic
Review and Meta-Analysis.
AB - Background: Cisplatin-based combination chemotherapy is standard treatment for
metastatic urothelial carcinoma; however, the vast majority of patients
experience disease progression. As systemic therapy alone is rarely curative for
the treatment of metastatic urothelial cancer, not only are new therapies needed
but also refinement of general treatment principles. Herein, we conducted a
systematic review and meta-analysis to explore the role of metastasectomy in
metastatic urothelial carcinoma. Methods: We conducted a systematic review of the
literature regarding local treatment for metastatic urothelial carcinoma. An
online electronic search of the PubMed/MEDLINE and EMBASE databases was performed
to identify peer-reviewed articles. All procedures were performed according to
the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
guidelines. Information was then extracted including number of patients, gender,
the site of the primary urothelial tumor, site of metastasis, chemotherapy before
or after metastasectomy, overall survival (OS), and disease specific survival
(DSS) after metastasectomy. A meta-analysis was performed with those studies with
sufficient survival data to obtain pooled overall survival. The article quality
was assessed using the Cochrane Handbook "risk of bias" tool. Results: Seventeen
out of 3963 articles were eligible for review between 1990-2015, including a
total of 412 patients. The mean time to recurrence after metastasectomy was 14.25
months. The overall survival from time of metastasectomy ranged from 2 to 60
months. Pooled analyses of studies reported survival data revealed an improved
overall survival for patients treated with metastasectomy compared with non
surgical treatment of metastatic lesions (HR 0.63; 95% CI, 0.49-0.81). All,
except for three studies, were retrospective and non-randomized, leading to a
high risk of bias associated with patient selection, patient attrition, and
reporting. Such high potential of selection bias may lead to higher OS than
expected. Additionally, treatment and outcome details reported across studies was
highly variable. Conclusions: Limited conclusions can be drawn from the available
literature exploring the role of metastasectomy in the management of metastatic
urothelial cancer due to lack of uniform reporting elements and multiple sources
of bias particularly related to a lack of prospective randomized trials. As a
subset of patients treated with metastasectomy achieve durable disease control,
this approach may be considered for select patients.
PMID- 28516159
TI - Challenging Cases in Urothelial Cancer.
PMID- 28516160
TI - Clinical Trials Corner.
PMID- 28516161
TI - Biallelic TOR1A variants in an infant with severe arthrogryposis.
PMID- 28516162
TI - Recognizing Academic Performance, Sleep Quality, Stress Level, and Mental Health
using Personality Traits, Wearable Sensors and Mobile Phones.
AB - What can wearable sensors and usage of smart phones tell us about academic
performance, self-reported sleep quality, stress and mental health condition? To
answer this question, we collected extensive subjective and objective data using
mobile phones, surveys, and wearable sensors worn day and night from 66
participants, for 30 days each, totaling 1,980 days of data. We analyzed daily
and monthly behavioral and physiological patterns and identified factors that
affect academic performance (GPA), Pittsburg Sleep Quality Index (PSQI) score,
perceived stress scale (PSS), and mental health composite score (MCS) from SF-12,
using these month-long data. We also examined how accurately the collected data
classified the participants into groups of high/low GPA, good/poor sleep quality,
high/low self-reported stress, high/low MCS using feature selection and machine
learning techniques. We found associations among PSQI, PSS, MCS, and GPA and
personality types. Classification accuracies using the objective data from
wearable sensors and mobile phones ranged from 67-92%.
PMID- 28516164
TI - Engineered ligand-based VEGFR antagonists with increased receptor binding
affinity more effectively inhibit angiogenesis.
AB - Pathologic angiogenesis is mediated by the coordinated action of the vascular
endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2
(VEGFR2) signaling axis, along with crosstalk contributed by other receptors,
notably alphavbeta3 integrin. We build on earlier work demonstrating that point
mutations can be introduced into the homodimeric VEGF ligand to convert it into
an antagonist through disruption of binding to one copy of VEGFR2. This inhibitor
has limited potency, however, due to loss of avidity effects from bivalent VEGFR2
binding. Here, we used yeast surface display to engineer a variant with VEGFR2
binding affinity approximately 40-fold higher than the parental antagonist, and
14-fold higher than the natural bivalent VEGF ligand. Increased VEGFR2 binding
affinity correlated with the ability to more effectively inhibit VEGF-mediated
signaling, both in vitro and in vivo, as measured using VEGFR2 phosphorylation
and Matrigel implantation assays. High affinity mutations found in this variant
were then incorporated into a dual-specific antagonist that we previously
designed to simultaneously bind to and inhibit VEGFR2 and alphavbeta3 integrin.
The resulting dual-specific protein bound to human and murine endothelial cells
with relative affinities of 120 +/- 10 pM and 360 +/- 50 pM, respectively, which
is at least 30-fold tighter than wild-type VEGF (3.8 +/- 0.5 nM). Finally, we
demonstrated that this engineered high-affinity dual-specific protein could
inhibit angiogenesis in a murine corneal neovascularization model. Taken
together, these data indicate that protein engineering strategies can be combined
to generate unique antiangiogenic candidates for further clinical development.
PMID- 28516163
TI - Engineered heparins as new anticoagulant drugs.
AB - Heparin is an anionic polysaccharide that is widely used as a clinical
anticoagulant. This glycosaminoglycan is prepared from animal tissues in metric
ton quantities. Animal-sourced heparin is also widely used in the preparation of
low molecular weight heparins that are gaining in popularity as a result of their
improved pharmacological properties. The recent contamination of pharmaceutical
heparin together with concerns about increasing demand for this life saving drug
and the fragility of the heparin supply chain has led the scientific community to
consider other potential sources for heparin. This review examines progress
toward the preparation of engineered heparins through chemical synthesis,
chemoenzymatic synthesis, and metabolic engineering.
PMID- 28516165
TI - Host- and pathogen-derived adjuvant coatings on protein nanoparticle vaccines.
AB - Nanoparticulate and molecular adjuvants have shown great efficacy in enhancing
immune responses, and the immunogenic vaccines of the future will most likely
contain both. To investigate the immunostimulatory effects of molecular adjuvants
on nanoparticle vaccines, we have designed ovalbumin (OVA) protein nanoparticles
coated with two different adjuvants-flagellin (FliC) and immunoglobulin M (IgM).
These proteins, derived from Salmonella and mice, respectively, are
representatives of pathogen- and host-derived molecules that can enhance immune
responses. FliC-coated OVA nanoparticles, soluble FliC (sFliC) admixed with OVA
nanoparticles, IgM-coated nanoparticles, and OVA-coated nanoparticles were
assessed for immunogenicity in an in vivo mouse immunization study. IgM coatings
on nanoparticles significantly enhanced both antibody and T cell responses, and
promoted IgG2a class switching but not affinity maturation. FliC-coated
nanoparticles and FliC-admixed with nanoparticles both triggered IgG2a class
switching, but only FliC-coated nanoparticles enhanced antibody affinity
maturation. Our findings that affinity maturation and class switching can be
directed independently of one another suggest that adjuvant coatings on
nanoparticles can be tailored to generate specific vaccine effector responses
against different classes of pathogens.
PMID- 28516166
TI - Onset and remodeling of coronal imbalance after selective posterior thoracic
fusion for Lenke 1C and 2C adolescent idiopathic scoliosis (a pilot study).
AB - BACKGROUND: Postoperative coronal imbalance is a significant problem after
selective thoracic fusion for primary thoracic and compensatory lumbar curves in
adolescent idiopathic scoliosis (AIS). However, longitudinal studies on
postoperative behavior of coronal balance are lacking. This multicenter
retrospective study was conducted to analyze factors related to onset and
remodeling of postoperative coronal imbalance after posterior thoracic fusion for
Lenke 1C and 2C AIS. METHODS: Twenty-one Lenke 1C or 2C AIS patients, who
underwent posterior thoracic fusion ending at L3 or above, were included with a
minimum 2-year follow-up. The mean patients' age was 15.1 years at the time of
surgery. Radiographic measurements were performed on Cobb angles of the main
thoracic (MT) and thoracolumbar/lumbar (TLL) curves and coronal balance. Factors
related to the onset of immediately postoperative coronal decompensation (IPCD)
and postoperative coronal balance remodeling (PCBR), defined as an improvement of
coronal balance during postoperative follow-up, were investigated using
comparative and correlation analyses. RESULTS: Mean Cobb angles for the MT and
TLL curves were 57.3 degrees and 42.3 degrees preoperatively and were corrected
to 22.8 degrees and 22.5 degrees at final follow-up, respectively. Mean
preoperative coronal balance of -3.8 mm got worse to -21.2 mm postoperatively,
and regained to -12.0 mm at final follow-up. Coronal decompensation was observed
in two patients preoperatively, in ten patients immediately postoperatively, and
in three patients at final follow-up. The preoperative coronal balance and lowest
instrumented vertebra (LIV) selection relative to stable vertebra (SV) were
significantly different between patients with IPCD and those without. PCBR had
significantly negative correlation with immediately postoperative coronal
balance. CONCLUSIONS: IPCD after posterior thoracic fusion for Lenke 1C and 2C
AIS was frequent and associated with preoperative coronal balance and LIV
selection. However, most patients with IPCD regained coronal balance through
PCBR, which was significantly associated with immediately postoperative coronal
balance. A fixation more distal to SV shifted the coronal balance further to the
left postoperatively.
PMID- 28516167
TI - Standardization of the modified Rodnan skin score for use in clinical trials of
systemic sclerosis.
AB - The modified Rodnan skin score (mRSS) is a measure of skin thickness and is used
as a primary or secondary outcome measure in clinical trials of systemic
sclerosis (scleroderma). This state-of-art review provides a historical
perspective of the development of the mRSS, summarizes the performance of mRSS as
an outcome measure, provides guidance on assessing mRSS, and makes
recommendations for incorporation of the mRSS into clinical trials.
PMID- 28516170
TI - Mott physics beyond Brinkman-Rice scenario.
AB - The main flaw of the well-known Brinkman-Rice description, obtained through the
Gutzwiller approximation, of the paramagnetic Mott transition in the Hubbard
model is in neglecting high-energy virtual processes that generate for instance
the antiferromagnetic exchange J ~ t2/U. Here we propose a way to capture those
processes by combining the Brinkman-Rice approach with a variational Schrieffer
Wolff transformation, and apply this method to study the single-band metal-to
insulator transition in a Bethe lattice with infinite coordination number, where
the Gutzwiller approximation becomes exact. We indeed find for the Mott
transition a description very close to the real one provided by dynamical mean
field theory; an encouraging result in view of possible applications to more
involved models.
PMID- 28516169
TI - Hybrid Pixel-Waveform (HPWF) Enabled CdTe Detectors for Small Animal Gamma-Ray
Imaging Applications.
AB - This paper presents the design and preliminary evaluation of small-pixel CdTe
gamma ray detectors equipped with a hybrid pixel-waveform (HPWF) readout system
for gamma ray imaging applications with additional discussion on CZT due to its
similarity. The HPWF readout system utilizes a pixelated anode readout circuitry
which is designed to only provide the pixel address. This readout circuitry works
in coincidence with a high-speed digitizer to sample the cathode waveform which
provides the energy, timing, and depth-of-interaction (DOI) information. This
work focuses on the developed and experimentally evaluated prototype HPWF-CdTe
detectors with a custom CMOS pixel-ASIC to readout small anode pixels of 350 MUm
in size, and a discrete waveform sampling circuitry to digitize the signal
waveform induced on the large cathode. The intrinsic timing, energy, and spatial
resolution were experimentally evaluated in this paper in conjunction with
methods for depth of interaction (DOI) partitioning of the CdTe crystal. While
the experimental studies discussed in this paper are primarily for evaluating
HPWF detectors for small animal PET imaging, these detectors could find their
applications for ultrahigh-resolution SPECT and other imaging modalities.
PMID- 28516168
TI - Selective Surface PEGylation of UiO-66 Nanoparticles for Enhanced Stability, Cell
Uptake, and pH-Responsive Drug Delivery.
AB - The high storage capacities and excellent biocompatibilities of metal-organic
frameworks (MOFs) have made them emerging candidates as drug-delivery vectors.
Incorporation of surface functionality is a route to enhanced properties, and
here we report on a surface-modification procedure-click modulation-that controls
their size and surface chemistry. The zirconium terephthalate MOF UiO-66 is (1)
synthesized as ~200 nm nanoparticles coated with functionalized modulators, (2)
loaded with cargo, and (3) covalently surface modified with poly(ethylene glycol)
(PEG) chains through mild bioconjugate reactions. At pH 7.4, the PEG chains endow
the MOF with enhanced stability toward phosphates and overcome the "burst
release" phenomenon by blocking interaction with the exterior of the
nanoparticles, whereas at pH 5.5, stimuli-responsive drug release is achieved.
The mode of cellular internalization is also tuned by nanoparticle surface
chemistry, such that PEGylated UiO-66 potentially escapes lysosomal degradation
through enhanced caveolae-mediated uptake. This makes it a highly promising
vector, as demonstrated for dichloroacetic-acid-loaded materials, which exhibit
enhanced cytotoxicity. The versatility of the click modulation protocol will
allow a wide range of MOFs to be easily surface functionalized for a number of
applications.
PMID- 28516171
TI - Boundary Negotiating Artifacts in Personal Informatics: Patient-Provider
Collaboration with Patient-Generated Data.
AB - Patient-generated data is increasingly common in chronic disease care management.
Smartphone applications and wearable sensors help patients more easily collect
health information. However, current commercial tools often do not effectively
support patients and providers in collaboration surrounding these data. This
paper examines patient expectations and current collaboration practices around
patient-generated data. We survey 211 patients, interview 18 patients, and re
analyze a dataset of 21 provider interviews. We find that collaboration occurs in
every stage of self-tracking and that patients and providers create boundary
negotiating artifacts to support the collaboration. Building upon current
practices with patient-generated data, we use these theories of patient and
provider collaboration to analyze misunderstandings and privacy concerns as well
as identify opportunities to better support these collaborations. We reflect on
the social nature of patient-provider collaboration to suggest future development
of the stage-based model of personal informatics and the theory of boundary
negotiating artifacts.
PMID- 28516172
TI - Supporting Patient-Provider Collaboration to Identify Individual Triggers using
Food and Symptom Journals.
AB - Patient-generated data can allow patients and providers to collaboratively
develop accurate diagnoses and actionable treatment plans. Unfortunately,
patients and providers often lack effective support to make use of such data. We
examine patient-provider collaboration to interpret patient-generated data. We
focus on irritable bowel syndrome (IBS), a chronic illness in which particular
foods can exacerbate symptoms. IBS management often requires patient-provider
collaboration using a patient's food and symptom journal to identify the
patient's triggers. We contribute interactive visualizations to support
exploration of such journals, as well as an examination of patient-provider
collaboration in interpreting the journals. Drawing upon individual and
collaborative interviews with patients and providers, we find that collaborative
review helps improve data comprehension and build mutual trust. We also find a
desire to use tools like our interactive visualizations within and beyond clinic
appointments. We discuss these findings and present guidance for the design of
future tools.
PMID- 28516173
TI - Reconsidering the Device in the Drawer: Lapses as a Design Opportunity in
Personal Informatics.
AB - People stop using personal tracking tools over time, referred to as the lapsing
stage of their tool use. We explore how designs can support people when they
lapse in tracking, considering how to design data representations for a person
who lapses in Fitbit use. Through a survey of 141 people who had lapsed in using
Fitbit, we identified three use patterns and four perspectives on tracking.
Participants then viewed seven visual representations of their Fitbit data and
seven approaches to framing this data. Participant Fitbit use and perspective on
tracking influenced their preference, which we surface in a series of contrasts.
Specifically, our findings guide selecting appropriate aggregations from Fitbit
use (e.g., aggregate more when someone has less data), choosing an appropriate
framing technique from tracking perspective (e.g., ensure framing aligns with how
the person feels about tracking), and creating appropriate social comparisons
(e.g., portray the person positively compared to peers). We conclude by
discussing how these contrasts suggest new designs and opportunities in other
tracking domains.
PMID- 28516174
TI - When Personal Tracking Becomes Social: Examining the Use of Instagram for Healthy
Eating.
AB - Many people appropriate social media and online communities in their pursuit of
personal health goals, such as healthy eating or increased physical activity.
However, people struggle with impression management, and with reaching the right
audiences when they share health information on these platforms. Instagram, a
popular photo-based social media platform, has attracted many people who post and
share their food photos. We aim to inform the design of tools to support healthy
behaviors by understanding how people appropriate Instagram to track and share
food data, the benefits they obtain from doing so, and the challenges they
encounter. We interviewed 16 women who consistently record and share what they
eat on Instagram. Participants tracked to support themselves and others in their
pursuit of healthy eating goals. They sought social support for their own
tracking and healthy behaviors and strove to provide that support for others.
People adapted their personal tracking practices to better receive and give this
support. Applying these results to the design of health tracking tools has the
potential to help people better access social support.
PMID- 28516177
TI - Insight into the phase evolution of a NiMgAl catalyst from the reduction stage to
the post-reaction stage during the dry reforming of methane.
AB - Herein, phase evolution of a NiMgAl oxide catalyst at the reduction stage was
qualitatively analysed and quantitatively determined by employing the continuous
changes in its XRD intensity and TPR information. The stable crystallite size of
both the active metal and spinel support was responsible for the long stability
of the NiMgAl catalyst without carbon deposition during the DRM reaction.
PMID- 28516175
TI - TummyTrials: A Feasibility Study of Using Self-Experimentation to Detect
Individualized Food Triggers.
AB - Diagnostic self-tracking, the recording of personal information to diagnose or
manage a health condition, is a common practice, especially for people with
chronic conditions. Unfortunately, many who attempt diagnostic self-tracking have
trouble accomplishing their goals. People often lack knowledge and skills needed
to design and conduct scientifically rigorous experiments, and current tools
provide little support. To address these shortcomings and explore opportunities
for diagnostic self-tracking, we designed, developed, and evaluated a mobile app
that applies a self-experimentation framework to support patients suffering from
irritable bowel syndrome (IBS) in identifying their personal food triggers.
TummyTrials aids a person in designing, executing, and analyzing self-experiments
to evaluate whether a specific food triggers their symptoms. We examined the
feasibility of this approach in a field study with 15 IBS patients, finding that
participants could use the tool to reliably undergo a self-experiment. However,
we also discovered an underlying tension between scientific validity and the
lived experience of self-experimentation. We discuss challenges of applying
clinical research methods in everyday life, motivating a need for the design of
self-experimentation systems to balance rigor with the uncertainties of everyday
life.
PMID- 28516176
TI - Examining Menstrual Tracking to Inform the Design of Personal Informatics Tools.
AB - We consider why and how women track their menstrual cycles, examining their
experiences to uncover design opportunities and extend the field's understanding
of personal informatics tools. To understand menstrual cycle tracking practices,
we collected and analyzed data from three sources: 2,000 reviews of popular
menstrual tracking apps, a survey of 687 people, and follow-up interviews with 12
survey respondents. We find that women track their menstrual cycle for varied
reasons that include remembering and predicting their period as well as informing
conversations with healthcare providers. Participants described six methods of
tracking their menstrual cycles, including use of technology, awareness of their
premenstrual physiological states, and simply remembering. Although women find
apps and calendars helpful, these methods are ineffective when predictions of
future menstrual cycles are inaccurate. Designs can create feelings of exclusion
for gender and sexual minorities. Existing apps also generally fail to consider
life stages that women experience, including young adulthood, pregnancy, and
menopause. Our findings encourage expanding the field's conceptions of personal
informatics.
PMID- 28516178
TI - A multi-walled carbon nanotube-zinc oxide nanofiber based flexible chemiresistive
biosensor for malaria biomarker detection.
AB - We report the fabrication of a flexible, lightweight and disposable multi walled
carbon nanotube (MWCNT)-zinc oxide (ZnO) nanofiber based chemiresistive biosensor
for label free detection of the malaria biomarker, histidine rich protein II
(HRP2). The sensing platform is formed by depositing nanofibers in between the
source and drain electrodes patterned on a thin, flexible polyethylene
terephthalate (PET) substrate. MWCNT-ZnO nanofibers are synthesized via the
electrospinning technique followed by a calcination process. This approach
creates functional groups on the nanofiber surface that are used for the one step
immobilization of HRP2 antibodies without further surface modification. The
device exhibits a good sensitivity of 8.29 kOmega g-1 mL and a wide detection
range of 10 fg mL-1-10 ng mL-1, and it is specific towards the targeted HRP2
biomarker. To the best of our knowledge, this is the first report on a flexible
chemiresistive biosensor explored for the detection of the malaria biomarker and
can be extended in the future to several other biomarker detection systems
towards smart point-of-care (POC) diagnostics.
PMID- 28516179
TI - alpha-Diazo oxime ethers for N-heterocycle synthesis.
AB - This Feature Article introduces the preparation and synthetic utility of alpha
diazo oxime ethers. alpha-Oximino carbenes are useful synthons for N
heterocycles, and can be easily prepared from alpha-diazo oxime ethers as
precursors. We begin with the preparation of alpha-diazo oxime ethers and their
application in [3+2] cycloaddition. It turns out that the nature of metals bound
to carbenes plays a crucial role in modulating the reactivity of alpha-oximino
carbenes, in which copper carbenes smoothly react with enamines, whereas the less
reactive enol ethers and nitriles require gold carbenes. In Section 3.2, a
discussion on N-O and C-H bond activation is presented. Carbenes derived from
diazo oxime ethers show unique reactivity towards N-O and C-H bond activation, in
which the proximity of the two functionalities, carbene and oxime ether, dictates
the preferred reaction pathways toward pyridines, pyrroles, and 2H-azirines. In
Section 3.3, the development of tandem reactions based on alpha-diazo oxime
ethers is discussed. The nature of carbenes in which whether free carbenes or
metal complexes are involved dissects the pathway and forms different types of 2H
azirines. The 2H-azirine formation turned out to be an excellent platform for the
tandem synthesis of N-heterocycles including pyrroles and pyridines. In the last
section, we describe the electrophilic activation of 2H-azirines with vinyl
carbenes and oximino carbenes. The resulting azirinium species undergo rapid ring
expansion rearrangements to form pyridines and pyrazines.
PMID- 28516180
TI - Near infrared two photon imaging using a bright cationic Yb(iii) bioprobe
spontaneously internalized into live cells.
AB - An Yb(iii) complex based on a dimethyl cyclen macrocyclic ligand functionalized
by charge transfer antennae was prepared. This cationic [YbL3]+ complex is stable
and soluble in water and presents interesting photophysical nonlinear properties.
It is spontaneously internalized and accumulates in live cells. High quality
images have been obtained both in a classical NIR-to-vis configuration and in the
more challenging NIR-to-NIR one.
PMID- 28516181
TI - A pulse electrosynthesized nanoporous nickel oxyhydroxide-borate thin film in
electro- and photoelectro-reforming of methanol for selective production of
formate.
AB - An nanoporous nickel oxyhydroxide-borate (NiBi) thin film, consisting of an
aggregate of spherical particles self-assembled from NiBi nanopetals, has been
synthesized using a simple and cost-effective pulse electrodeposition method
without the addition of any surfactant, and demonstrated as an efficient,
selective, and robust electrocatalyst in the electrochemical and
photoelectrochemical reforming of methanol into formate.
PMID- 28516182
TI - Intracellular accumulation and immunological responses of lipid modified magnetic
iron nanoparticles in mouse antigen processing cells.
AB - Understanding the effects of magnetic iron nanoparticles (MINPs) on the immune
response is vitally important for biomedical applications such as cancer therapy,
disease diagnosis and novel cancer imaging. In this study, lipid modified MINPs
were designed and prepared by introducing the neutral lipid DSPE-PEG or the
zwitterionic lipid DSPE-PCB into hydrophobic MINPs through hydrophobic
interaction (L-MINPs and ZL-MINPs, respectively). The effect of L-MINPs and ZL
MINPs on the intracellular accumulation and immune responses of three kinds of
antigen processing cells was examined. The results indicated that the high
cellular uptake efficiency of surface coated MINPs was strongly related to the
nature of the coating lipid, with the zwitterionic lipid being more effective
than PEGylated ones. Besides, the results from flow cytometry (FCM), confocal
laser scanning microscopy (CLSM) and Prussian blue staining demonstrated a time-
and concentration-dependent MINP internalization. The uptake of zwitterionic
lipid modified MINPs (ZL-MINPs) induced very low cytotoxicity and a strong mixed
Th1/Th2 type immune response. L-MINPs could induce a strong increase in pro
inflammatory cytokines with a slight secretion of Th2 cytokines. Besides, no IL
10 was observed in both groups, indicating that MINPs with lipid modification
were absence of immunosuppression. In conclusion, this study addresses an
important implication of the lipid type and Fe concentration on the immune
stimulation of cells and supports the potential for further development of
biomedical applications.
PMID- 28516187
TI - [The aged scalp : A dermato-oncological focus point].
AB - Non-melanoma skin cancer and its precursor lesions are common diagnoses in
dermatological practice, due to rising incidence and prevalence. Diagnosis is
often clinical with subsequent histological confirmation. First-choice treatment
for invasive carcinomas is complete surgical excision. Other therapeutic options,
such as radiation or systemic therapies, should only be considered when excision
is impossible. Mostly located on parts of the scalp that are poorly visible and
accessible, particularly for elderly patients, these lesions are a challenge for
physicians and patients alike. Especially regarding precursor lesions, the
therapeutic options are numerous and should be adapted to the individual patient.
The main risk factor for development of non-melanoma skin cancer and its
precursor lesions is chronic UV exposure. A possible occupational context should
always be considered. Preventative methods based on patient education and
adequate sun protection behavior are particularly important. The prognosis of non
melanoma skin cancer improves significantly with early diagnosis, as well as with
guideline-compatible treatment and follow-up.
PMID- 28516190
TI - [Is there still a role for active surveillance in prostate cancer?]
AB - Long-term data demonstrate a higher oncological risk associated with active
surveillance (AS) than initially anticipated. In particular, patients with more
than two tumor-involved biopsy cores and/or Gleason-7a foci must be regarded as
having an increased risk of developing an incurable stage of disease after an
initial attempt of AS. For patients with Gleason-7a foci, the 15-year risk of
suffering from an incurable tumor stage is reported as high as 60%. Furthermore,
life expectancy must be regarded as one of the major risk factors to finally
develop symptomatic incurable disease. A discussion has therefore started as to
whether a high life expectancy should be regarded as an exclusion criterion
against AS. An estimated life expectancy exceeding 15 or 20 years has been
proposed for patients suffering from Gleason 7a or 6 foci at initial biopsy,
respectively. Furthermore, it must be expected that a number of molecular risk
factors will gain importance in the near future for the decision-making process
for or against AS.
PMID- 28516191
TI - [Unexpected finding in a case of oculomotor nerve paresis].
PMID- 28516188
TI - Management of bilateral Wilms tumours.
AB - Wilms tumour is named after Max Wilms. It is an embryonal tumour derived from the
metanephros. It is the commonest childhood renal tumour and the third commonest
paediatric malignancy. Synchronous bilateral Wilms tumours (BWT) represent 4-7%
of all Wilms tumours (WT) and present at a younger age than unilateral Wilms
tumours. At least 10% of synchronous BWTs have unfavourable histology, and up to
22% are associated with genitourinary abnormalities, aniridia, WAGR syndrome,
Denys-Drash syndrome, hemihypertrophy, or one of the other overgrowth syndromes.
The long-term disease-free survival rate for patients with unilateral WT is
approaching 90%, and is around 70% for those with metastatic disease. For both
synchronous and metachronous Wilms tumours the prognosis is less favourable with
reported cure rates approaching 80% in the best centres and lower in resource
poor settings. There is potential for a reduced quality of life due to renal
insufficiency and the possible need for renal transplantation. The major clinical
challenge in BWTs is preservation of functioning renal tissue using nephron
sparing surgical techniques, while achieving cure with minimum therapy-related
morbidity. Mortality is generally associated with progressive disease of
anaplastic tumours. Chemotherapy followed by nephron-sparing surgery has been
able, in most cases, to eradicate the tumour while preserving renal function.
Radiotherapy has largely been avoided because of fears of long-term radiation
injury to the residual functioning renal mass. Patient selection, appropriate pre
and post-operative chemotherapy and skilled surgical techniques all contribute
to excellent outcomes where these are achievable.
PMID- 28516189
TI - Improving the rigour of VACTERL screening for neonates with anorectal
malformations.
AB - PURPOSE: Screening investigations for the vertebral, anorectal, cardiac, tracheo
oesophageal, renal and limb (VACTERL) association form an important part of the
management of neonates with anorectal malformations (ARMs). We developed a
proforma to define investigations and indications for referral. The aim of the
current study was to determine if the proforma could improve screening rigour.
METHODS: Four centres performed a 3-year retrospective audit of neonates with
ARM. Following introduction of a proforma, the same data were collected
prospectively for consecutive neonates over a further 2 years. The appropriate
investigation of each component of the VACTERL association and the corresponding
referral required for each abnormal result were defined. The proportion of
patients undergoing appropriate investigation and referral was compared against
these standards. An audit standard of 90% was set for each criteria. RESULTS:
Prior to implementation of the proforma, 86 patients were audited, with a further
69 patients after. The audit standard was met in 7 criteria before introduction
of the proforma in comparison to 10 criteria afterwards. CONCLUSION: The
completeness of VACTERL screening and its documentation improved following
introduction of the proforma. Performance remains imperfect. Review of specific
criteria (such as definition of vertebral body screening) will help address this.
PMID- 28516192
TI - The value of Gesell score in predicting the outcome of cochlear implantation in
children.
AB - The purpose is to determine the value of preoperative evaluation on developmental
levels using Gesell score in predicting the postoperative outcome in pediatric
cochlear implantation (CI) recipients. 78 children who underwent CI were included
in our study. Age at the time of CI ranged from 6 to 67 months. The Gesell score
including adaptability, fine motor, gross motor, language, and social skill was
used for evaluating the patients' developmental levels before the CI, and a
developmental quotient (DQ) was calculated by the following formula:
(developmental age/actual age) * 100. The auditory perception and speech
production abilities were evaluated using the categories of auditory performance
(CAP) and speech intelligibility rating (SIR) before CI and at 1 year after CI.
The associations between the preoperative Gesell score/DQ and the improvement of
postoperative CAP/SIR outcomes were analyzed. Preoperative developmental
evaluation of CI candidates suggested that the developmental delay was common in
children with profound hearing loss. The mean of language DQ (46.72 +/- 17.59)
was significantly decreased than the mean of others' ability DQ in the enrolled
children. The older the pediatric CI candidates were, the lower the DQ were.
Age/adaptability DQ and improvement of postoperative CAP/SIR 1 year after CI were
related. Age was negative correlation with the CI outcome and adaptability DQ was
positive correlation with the CI outcome. The mean of CAP 1 year after CI was
4.16, and the mean of SIR 1 year after CI was 2.03. The first logistics
regression equation was Y1 = exp (-18.123 + 0.199 * adaptability DQ - 0.163 *
age), and Y1 was the possibility which CAP was lower than 5 1 year after CI. The
sensitivity of first regression equation was 84.2% and specificity was 70.8%. The
second logistics regression equation was Y2 = exp (-23.347 + 0.268 * adaptability
DQ - 0.164 * age), and Y2 was the possibility which SIR was lower than 3 1 year
after CI. The sensitivity of second regression equation was 85.7% and specificity
was 72.7%. Preoperative Gesell score may be value in predicting the postoperative
outcome in pediatric CI recipients. The older children are more serious
developmental delay occur, so the CI operation should be finished as early as
possible. Adaptability DQ combined with age has predictive effect on the
postoperative outcome of cochlear implantation in children.
PMID- 28516194
TI - [Current legal and jurisdictional questions from the perspective of the German
Federal Association for Geriatrics : Practical report].
AB - The article discusses the questions of the arbitration bodies according to S 111b
SGB V (Volume V of the Social Insurance Code) in the individual federal states
from the perspective of geriatric rehabilitation hospitals. The content of the
agreement of reimbursement between a rehabilitation hospital and health insurance
will be targeted as well as the question whether the entire content of the
agreements of reimbursement can be negotiated at the arbitration body. In
addition, the authors describe the consequences of the jurisprudence of the
Federal Social Court on S 301 I. S. 1 no. 8 SGB V and the reaction of the
lawgiver. Furthermore the authors describe the effects of the jurisprudence of
the Federal Social Court regarding the minimum age associated with complex
geriatric treatment (OPS 8-550).
PMID- 28516193
TI - Co-mutated CALR and MPL driver genes in a patient with myeloproliferative
neoplasm.
PMID- 28516195
TI - [10-year anniversary of the Long-term Care Charter : Time to take stock].
AB - Ten years ago, the Charter for People in Need of Long-term Care was published in
Germany. The Charter contains a series of basic rights for people in need of long
term care. At the initiative of the Federal Ministry for Family Affairs, Senior
Citizens, Women and Youth (BMFSFJ), this was developed in a complex consensus
process together with the Federal Ministry of Health (BMG) and representatives
from all areas of care. Since then, the Charter has gained practical relevance in
various areas of care and has entered into legislation. The article looks at the
dissemination and impact of the Charter following a review of the social and
legal environment. Further implementation requirements and the revision of the
charter are discussed.
PMID- 28516197
TI - Optimized immunohistochemistry using the D5F3 antibody provides a reliable test
for identification of ALK-positive lung adenocarcinomas.
AB - We used optimized immunohistochemistry (IHC) with the D5F3 antibody for detection
of tumours in a prospective study of 307 pulmonary adenocarcinomas. Cases
positive by IHC (1+, 2+, 3+) were further investigated by fluorescent in situ
hybridization (FISH). Of 307 cases, 22 (7.2%) were moderately intensely positive
(2+/3+); 18 of these (82%) were also positive by FISH. Of the four IHC
positive/FISH-negative cases, one was unsuitable for FISH and three had
abnormalities of the ALK gene. All cases with weak reactivity with D5F3 (1+) were
FISH-negative. The FISH positive/IHC-positive cases with moderately intense
reactivity had the typical clinicopathologic features of ALK-positive patients
(younger age, p < 0.01; higher frequency in metastatic sites, p < 0.01;
cribriform/mucinous/signet histology, p < 0.01; stage IV disease, p < 0.01). In
conclusion, our findings indicate that optimized IHC using the D5F3 antibody
provides a reliable and inexpensive test for identification of ALK-positive
adenocarcinomas. Inclusion of this information in the pathology report at the
time of the histological diagnosis might significantly shorten time to treatment.
PMID- 28516198
TI - [Local consolidative therapy improves progression-free survival in patients with
oligometastatic NSCLC : Results of a randomized phase II study].
PMID- 28516196
TI - Coupling dynamics in speech gestures: amplitude and rate influences.
AB - Speech is a complex oral motor function that involves multiple articulators that
need to be coordinated in space and time at relatively high movement speeds. How
this is accomplished remains an important and largely unresolved empirical
question. From a coordination dynamics perspective, coordination involves the
assembly of coordinative units that are characterized by inherently stable
coupling patterns that act as attractor states for task-specific actions. In the
motor control literature, one particular model formulated by Haken et al. (Biol
Cybern 51(5):347-356, 1985) or HKB has received considerable attention in the way
it can account for changes in the nature and stability of specific coordination
patterns between limbs or between limbs and external stimuli. In this model (and
related versions), movement amplitude is considered a critical factor in the
formation of these patterns. Several studies have demonstrated its role for
bimanual coordination and similar types of tasks, but for speech motor control
such studies are lacking. The current study describes a systematic approach to
evaluate the impact of movement amplitude and movement duration on coordination
stability in the production of bilabial and tongue body gestures for specific
vowel-consonant-vowel strings. The vowel combinations that were used induced a
natural contrast in movement amplitude at three speaking rate conditions (slow,
habitual, fast). Data were collected on ten young adults using electromagnetic
articulography, recording movement data from lips and tongue with high temporal
and spatial precision. The results showed that with small movement amplitudes
there is a decrease in coordination stability, independent from movement
duration. These findings were found to be robust across all individuals and are
interpreted as further evidence that principles of coupling dynamics operate in
the oral motor control system similar to other motor systems and can be explained
in terms of coupling mechanisms between neural oscillators (organized in
networks) and effector systems. The relevance of these findings for understanding
motor control issues in people with speech disorders is discussed as well.
PMID- 28516199
TI - Cloning and Stress-Induced Expression Analysis of Calmodulin in the Antarctic
Alga Chlamydomonas sp. ICE-L.
AB - Calmodulin (CaM) is a Ca2+-binding protein that plays a role in several Ca2+
signaling pathways, which dynamically regulates the activities of hundreds of
proteins. The ice alga Chlamydomonas sp. ICE-L, which has the ability to adapt to
extreme polar conditions, is a crucial primary producer in Antarctic ecosystem.
This study hypothesized that Cam helps the ICE-L to adapt to the fluctuating
conditions in the polar environment. It first verified the overall length of Cam,
through RT-PCR and RACE-PCR, based on partial Cam transcriptome library of ICE-L.
Then, the nucleotide and predicted amino acid sequences were, respectively,
analyzed by various bioinformatics approaches to gain more insights into the
computed physicochemical properties of the CaM. Potential involvements of Cam in
responding to certain stimuli (i.e., UVB radiation, high salinity, and
temperature) were investigated by differential expression, measuring its
transcription levels by means of quantitative RT-PCR. Results showed that CaM was
indeed inducible and regulated by high UVB radiation, high salinity, and
nonoptimal temperature conditions. Different conditions had different expression
tendencies, which provided an important basis for investigating the adaptation
mechanism of Cam in ICE-L.
PMID- 28516200
TI - Respiratory viral infections are underdiagnosed in patients with suspected
sepsis.
AB - The study aim was to investigate the prevalence and clinical relevance of viral
findings by multiplex PCR from the nasopharynx of clinically septic patients
during a winter season. During 11 weeks of the influenza epidemic period in
January-March 2012, consecutive adult patients suspected to be septic (n = 432)
were analyzed with cultures from blood and nasopharynx plus multiplex PCR for
respiratory viruses on the nasopharyngeal specimen. The results were compared
with those from microbiology analyses ordered as part of standard care. During
the winter season, viral respiratory pathogens, mainly influenza A virus, human
metapneumovirus, coronavirus, and respiratory syncytial virus were clinically
underdiagnosed in 70% of patients positive by the multiplex PCR assay. During the
first four weeks of the influenza epidemic, few tests for influenza were ordered
by clinicians, indicating low awareness that the epidemic had started.
Nasopharyngeal findings of Streptococcus pneumoniae and Haemophilus influenzae by
culture correlated to pneumonia diagnosis, and in those patients laboratory signs
of viral co-infections were common but rarely suspected by clinicians. The role
of respiratory viral infections in patients presenting with a clinical picture of
sepsis is underestimated. Specific antiviral treatment might be beneficial in
some cases and may reduce spread in a hospital setting. Diagnosing viral
infections may promote reduction of unnecessary antibiotic use. It can also be a
tool for decisions concerning patient logistics, in order to minimize exposure of
susceptible patients and personnel.
PMID- 28516201
TI - Budget impact and cost-effectiveness analyses of direct-acting antivirals for
chronic hepatitis C virus infection in Hong Kong.
AB - The purpose of this investigation was to evaluate the budget impact and cost
effectiveness of direct-acting antivirals (DAAs) for the treatment of hepatitis C
virus (HCV) infection in Hong Kong. A decision analytic model was developed to
compare short-term costs and health outcomes of patients with chronic HCV
genotype 1 infection in Hong Kong who were treated with an interferon (INF)-based
treatment (dual therapy of pegylated interferon and ribavirin) or DAA-based
treatments (sofosbuvir or ledipasvir/sofosbuvir or
ombitasvir/paritaprevir/ritonavir plus dasabuvir). Compared to INF-based
treatment, DAA-based treatments yielded an incremental cost of $24,677-$31,171
per course while improving the rate of sustained virologic response (SVR) from 59
66% to 82.3-99.8%. The incremental cost-effective ratios of DAA-based treatments
ranged from $9724 to $29,189 per treatment success, which were all below the cost
effectiveness threshold of local GDP per capita ($42,423 in 2015). Introducing
DAAs resulted in a 126.1% ($383.7 million) budget increase on HCV infection
management over 5 years. A 50% change in DAA medication costs reflected a change
in the incremental budget from $55.2 to $712.3 million. DAA-based treatments are
cost-effective alternatives to INF-based treatment in Hong Kong. Introducing DAAs
to the public hospital formulary yields a considerable budget increase but is
still economically favorable to the local government.
PMID- 28516203
TI - [Erratum to: Surgical anatomy of the abdominal wall].
PMID- 28516202
TI - [Plastic reconstruction of radiation injuries].
AB - In addition to surgical and drug therapy, radiotherapy (or radiation therapy) is
one of the three mainstays of modern oncological therapy regimes. It uses
ionizing radiation to control tumors by damaging the DNA of cancerous tissue
leading to cellular death. Although advances have been made in recent years
resulting in a reduced dosage to the surrounding tissues, radiation injuries and
tissue-related side effects cannot be completely avoided. Knowledge of the
pathophysiology, treatment modalities and interdisciplinary treatment approaches
are essential for effective therapy whilst limiting side effects. Surgery within
the irradiated area is technically demanding due to tissue alterations and
unpredictable wound healing. The plastic reconstructive surgeon either faces the
challenge of delayed wound healing following neoadjuvant radiation or chronic
radiation-linked changes following previous radiotherapy, which can also occur
after a latency period of many years. Reconstructive interventions can be
essential to repair deficits of a functional and/or aesthetic nature in order to
maintain a high quality of life for oncology patients. This can also be of
benefit to patients in a palliative oncological setting to improve daily
functions and quality of life.
PMID- 28516205
TI - Applications of white rot fungi in bioremediation with nanoparticles and
biosynthesis of metallic nanoparticles.
AB - White rot fungi (WRF) are important environmental microorganisms that have been
widely applied in many fields. To our knowledge, the application performance of
WRF in bioremediation can be greatly improved by the combination with
nanotechnology. And the preparation of metallic nanoparticles using WRF is an
emerging biosynthesis approach. Understanding the interrelation of WRF and
nanoparticles is important to further expand their applications. Thus, this mini
review summarizes the currently related reports mainly from the two different
point of views. We highlight that nanoparticles as supports or synergistic agents
can enhance the stability and bioremediation performance of WRF in wastewater
treatment and the biosynthesis process and conditions of several important
metallic nanoparticles by WRF. Furthermore, the potential toxicity of
nanoparticles on WRF and challenges encountered are also discussed. Herein, we
deem that this mini-review will strengthen the basic knowledge and provide
valuable insight for the applications of WRF and nanoparticles.
PMID- 28516204
TI - A Novel, Dynamic Statistical Model for Predicting Patient Satisfaction with
Fundoplication Based on Pre-Operative Symptom Patterns.
AB - BACKGROUND: Fundoplication provides excellent control of gastro-oesophageal
reflux disease (GORD), but there remain a number of unsatisfied patients who have
proven difficult to identify pre-operatively. We hypothesised that pre-operative
symptom patterns can predict of the risk of post-operative dissatisfaction.
METHODS: Pre-operative symptoms and post-operative satisfaction were measured
using standardised questionnaires along with routine investigations. These data
were used to calculate our novel pre-operative risk of dissatisfaction (PROD)
score. Potential pre-operative prognostic markers were tested against the post
operative satisfaction data, including the objective investigations and the PROD
score. The prognostic utility of the PROD score and the Society of American
Gastrointestinal and Endoscopic Surgeons (SAGES) guideline was tested using
receiver operating characteristic analysis to determine the area under the curve
(AUC). RESULTS: An association was found between our PROD score and each of the
satisfaction measures (n = 225, p < 0.001) which is likely to be of prognostic
utility (AUC = 0.67-0.79). No such association was found between the routine
investigations and post-operative satisfaction. The PROD score was found to be of
greater prognostic utility than the SAGES guideline (n = 166, p < 0.001).
CONCLUSIONS: The PROD score is a novel, easy-to-use test that can predict
individual patient satisfaction with fundoplication.
PMID- 28516206
TI - Identification, expression and characterization of an R-omega-transaminase from
Capronia semiimmersa.
AB - Chiral amines are essential precursors in the production of biologically active
compounds, including several important drugs. Among the biocatalytic strategies
that have been developed for their synthesis, the use of omega-transaminases
(omega-TA) appears as an attractive alternative allowing the stereoselective
amination of prochiral ketones. However, the problems associated with narrow
substrate specificity, unfavourable reaction equilibrium and expensive amine
donors still hamper its industrial application. The search for novel enzymes from
nature can contribute to expand the catalytic repertoire of omega-TA and help to
circumvent some of these problems. A genome mining approach, based on the work
described by Hohne et al., was applied for selection of potential R-omega-TA.
Additional criteria were used to select an enzyme that differs from previously
described ones. A candidate R-omega-TA from Capronia semiimmersa was selected,
cloned and expressed in Escherichia coli. Interestingly, alignment of this enzyme
with previously reported TA sequences revealed the presence of two additional
amino acid residues in a loop close to the active site. The impact of this change
was analysed with a structural model based on crystallized R-omega-TAs. Analysis
of the substrate specificity of R-omega-TA from C. semiimmersa indicates that it
accepts a diversity of ketones as substrates yielding the corresponding amine
with good yields and excellent enantioselectivity. The expressed enzyme accepts
isopropylamine as amine donor what makes it suitable for industrial processes.
PMID- 28516207
TI - Enhancing H2O2 resistance of an esterase from Pyrobaculum calidifontis by
structure-guided engineering of the substrate binding site.
AB - Green technologies are attracting increasing attention in industrial chemistry
where enzymatic reactions can replace dangerous and environmentally unfriendly
chemical processes. In situ enzymatic synthesis of peroxycarboxylic acid is an
attractive alternative for several industrial applications although concentrated
H2O2 can denature the biocatalyst, limiting its usefulness. Herein, we report the
structure-guided engineering of the Pyrobaculum calidifontis esterase (PestE)
substrate binding site to increase its stability and perhydrolysis activity. The
L89R/L40A PestE mutant showed better tolerance toward concentrated H2O2 compared
with wild-type PestE, and retained over 72% of its initial activity after 24-h
incubation with 2 M H2O2. Surprisingly, the half-life (t 1/2, 80 degrees C) of
PestE increased from 28 to 54 h. The k cat/K m values of the mutant increased 21-
and 3.4-fold toward pentanoic acid and H2O2, respectively. This work shows how
protein engineering can be used to enhance the H2O2 resistance and catalytic
efficiency of an enzyme.
PMID- 28516208
TI - Safety and efficiency of active immunization with detoxified antigen against
scorpion venom: side effect evaluation.
AB - OBJECTIVE: The efficiency and safety of vaccine are the most important
properties, however, as any medication, it can induce side effects. This
prophylactic therapy could be used to prevent the lethal and pathophysiological
effects induced after scorpion envenomation. METHODS: In this study, detoxified
venom associated to alum adjuvant (V*alum) is used as a vaccine against scorpion
venom for immunization of mice. We evaluate the safety and the inflammatory
response of this vaccine. We also investigated the protective effect of this
formulation against the toxicity of native Androctonus australis hector venom.
RESULTS: Results showed no adverse events occurred after immunization of animals.
This active immunization of animals did not cause change in vascular
permeability, no edema formation in the studied organs. Furthermore, there are no
IgE production in sera, nor change in the morphology of the mast cells in skin
tissues. However, low inflammatory response triggered by activating the
recruitment of eosinophils associated to IL-4 and IL-5 release was observed. All
immunized animals are protected from the toxic effects of native venom until 6
LD50 and to 7 LD50 after the second challenge. CONCLUSION: This safe vaccine
preparation seems to induce a long-term protection without any risk of
deleterious inflammatory response.
PMID- 28516209
TI - Foreign Language Effect and Psychological Distance.
AB - Does using a foreign language result in forming different moral decisions than
using our mother tongue? Two studies were conducted to investigate whether there
is a relationship between foreign language effects (differences between native
vs. foreign language conditions) and psychological distance. Study 1 tested four
moral dilemmas adapted from Greene et al. (Cognition 107: 1144-1155, 2008). Non
fluent Korean-English bilingual participants (N = 161) indicated decisions
regarding four moral dilemmas in either Korean or English languages. The study
found that for personal moral conflict situations, in which emotion and automatic
intuition were more important than deliberation, there were significant
differences in ratios of utilitarian decisions between the native language (L1)
and the foreign language (L2) conditions. The participants tended to make more
utilitarian decisions in L2 than in L1, which implies reduced emotionality in L2.
Study 2 examined whether the psychological distance increased using the foreign
language (English) utilizing an automatic self-test. Nonproficient Korean-English
bilinguals (N = 26) formed associations between three kinds of geometric shapes
(ellipses, rectangles and triangles) and three kinds of labels ('me', 'friends'
and 'others'). The results of the study found the self-bias effect decreased when
labels were presented in the foreign language (in English). This implies that the
foreign language effect resulted from the reduced emotional response, and
deliberation in decision making which may result from increased psychological
distance.
PMID- 28516210
TI - Antibiotic resistance genes in surface water of eutrophic urban lakes are related
to heavy metals, antibiotics, lake morphology and anthropic impact.
AB - Urban lakes are impacted by heavy human activities and represent potential
reservoirs for antibiotic resistance genes. In this study, six urban lakes in
Wuhan, central China were selected to analyze the distribution of sulfonamide
resistance (sul) genes, tetracycline resistance (tet) genes and quinolone
resistance (qnr) genes and their relationship with heavy metals, antibiotics,
lake morphology and anthropic impact. sul1 and sul2 were detected in all six
lakes and dominated the types of antibiotic resistance genes, which accounted for
86.28-97.79% of the total antibiotic resistance gene abundance. For eight tested
tet genes, antibiotic efflux pumps (tetA, tetB, tetC, and tetG) genes were all
observed in six lakes and had higher relative abundance than ribosomal protection
protein genes (tetM and tetQ). For 4 plasmid mediated quinolone resistance genes,
only qnrD is found in all six lakes. The class I integron (intI1) is also found
to be a very important media for antibiotic resistance gene propagation in urban
lakes. The results of redundancy analysis and variation partitioning analysis
showed that antibiotic and co-selection with heavy metals were the major factors
driving the propagation of antibiotic resistance genes in six urban lakes. The
heavily eutrophic Nanhu Lake and Shahu Lake which located in a high density
building area with heavy human activities had the higher relative abundance of
total antibiotic resistance genes. Our study could provide a useful reference for
antibiotic resistance gene abundance in urban lakes with high anthropic impact.
PMID- 28516211
TI - Early endothelialization associated with a biolimus A9 bioresorbable polymer
stent in a porcine coronary model.
AB - Although Nobori(r), with a bioresorbable polymer and biolimus A9 abluminal
coating, has unique characteristics, few data exist regarding endothelialization
early after implantation. Fifteen Nobori(r) and 14 control bare-metal stents (S
stentTM) were implanted in 12 pigs. Histopathology of stented segments,
inflammation, and intimal fibrin content was evaluated on the 2nd and 14th day
after implantation. On the 2nd day, endothelial cells were morphologically and
immunohistologically confirmed on the surface of both stents, although some
inflammatory cells might be involved. Stent surface endothelialization evaluated
with a scanning electron microscope showed partial cellular coverage in both
stents. On the 14th day, neointimal thickness and percentage of the neointimal
area were significantly lower in Nobori(r) than in S-stentTM (51.4 +/- 4.5 vs.
76.4 +/- 23.6 um, p < 0.05 and 10.8 +/- 2.6 vs. 14.1 +/- 4.2%, p < 0.01). No
significant differences were found in these parameters on the 2nd day (17.3 +/-
14.9 vs. 26.7 +/- 13.6 um and 3.7 +/- 3.0 vs. 6.7 +/- 3.7%), in inflammatory and
intimal fibrin content scores. These results demonstrate that endothelialization
could occur early after Nobori(r) implantation with similar inflammatory reaction
to bare-metal stents, probably contributing to low frequency of in-stent
thrombosis and restenosis.
PMID- 28516213
TI - Expression of Concern: Aspirin attenuates insulin resistance in muscle of diet
induced obese rats by inhibiting inducible nitric oxide synthase production and S
nitrosylation of IRbeta/IRS-1 and Akt.
PMID- 28516212
TI - Anatomical visualization of neural course and distribution of anterior ascending
aortic plexus.
AB - The aim of this study was to document the detailed anatomy of neural course and
distribution on the anterior ascending aorta, to identify the high and low
density areas of the anterior ascending aortic plexus for further understandings
in cardiovascular surgery. The embalmed hearts of 42 elderly individuals were
submacroscopically and microscopically examined, after excluding any that were
macroscopically abnormal. With its origins in the anterior ascending aortic
plexus, the right coronary plexus substantially innervated the right coronary
artery, the right atrium and ventricle, and the sinus node. The intensive neural
area extending from 10 mm lateral to the interatrial groove below the pericardial
reflection as far as the right coronary artery opening contained almost all the
right coronary plexus in 61.3% of patients, and more than 40.9% of the total
nerve volume of the anterior ascending aortic plexus. Our findings suggest that
the most superior and lateral area on the ascending aorta show the lowest neural
density of right coronary component in the anterior ascending aortic plexus and
the high density areas are invisible in right lateral field of view as seen in
the right trans-axillary MICS approach.
PMID- 28516214
TI - Interactions of cisplatin and the copper transporter CTR1 in human colon cancer
cells.
AB - There is much interest in understanding the mechanisms by which platinum-based
anticancer agents enter cells, and the copper transporter CTR1 has been the focus
of many recent studies. While there is a clinical correlation between CTR1 levels
and platinum efficacy, cellular studies have provided conflicting evidence
relating to the relationship between cisplatin and CTR1. We report here our
studies of the relationship between cisplatin and copper homeostasis in human
colon cancer cells. While the accumulation of copper and platinum do not appear
to compete with each other, we did observe that cisplatin perturbs CTR1
distribution within 10 min, a far shorter incubation time than commonly employed
in cellular studies of cisplatin. Furthermore, on these short time-scales,
cisplatin caused an increase in the cytoplasmic labile copper pool. While the
predominant focus of studies to date has been on CTR1, these studies highlight
the importance of investigating the interaction of cisplatin with other copper
proteins.
PMID- 28516216
TI - The role of intrauterine magnetic resonance in the management of myelomenigocele.
AB - OBJECTIVE: To assess the role of magnetic resonance imaging (MRI) in the
management of myelomenigocele. BACKGROUND: Spinal dysraphism or neural tube
defects (NTD) encompass a heterogeneous group of congenital spinal anomalies that
result from the defective closure of the neural tube early in gestation.
Myelomeningocele is the most common type of NTD that is compatible with life,
with high survival rates but lifelong physical impairments. CONCLUSION: MRI is an
important adjunct to ultrasound in assessing NTD, as it pertains to pre-surgical
planning and perinatal management. However, it should not be considered a
replacement for ultrasonography, which continues to be the gold standard for
fetal anatomic evaluation.
PMID- 28516215
TI - Are clinical findings of systemic titanium dispersion following implantation
explained by available in vitro evidence? An evidence-based analysis.
AB - Although the presence of titanium wear particles released into tissues is known
to induce local inflammation following the therapeutic implantation of titanium
devices into humans, the role that titanium ions play in adverse tissue responses
has received little attention. Support that ongoing titanium ion release occurs
is evidenced by the presence of ionic titanium bound to transferrin in blood, and
ongoing excretion in the urine of patients with titanium devices. However, as
reports documenting the presence of titanium within tissues do not distinguish
between particulate and ionic forms due to technical challenges, the degree to
which ionic titanium is released into tissues is unknown. To determine the
potential for titanium ion release into tissues, this study evaluates available
in vitro evidence relating to the release of ionic titanium under physiological
conditions. This is a systematic literature review of studies reporting titanium
ion release into solutions from titanium devices under conditions replicating the
interstitial pH and constituents. Inclusion and exclusion criteria were defined.
Of 452 articles identified, titanium ions were reported in nine media relevant to
human biology in seventeen studies. Only one study, using human serum replicated
both physiological pH and the concentration of constituents while reporting the
presence of titanium ions. While there is insufficient information to explain the
factors that contribute to the presence of titanium ions in serum of humans
implanted with titanium devices, currently available information suggests that
areas of future inquiry include the role of transferrin and organic acids.
PMID- 28516217
TI - Prenatal surgery for myelomeningocele: review of the literature and future
directions.
AB - Open spina bifida or myelomeningocele (MMC) is one of the most common serious
congenital malformations. Historically, this condition has been treated with
closure of the MMC defect shortly after birth. The goal of postnatal closure is
to cover the exposed spinal cord and prevent infection. However, postnatal
surgery does not reverse or prevent the neurologic injury seen in MMC, reverse
hindbrain herniation, or prevent hydrocephalus. The neurologic defects result
from primary incomplete neurulation and secondary chronic prenatal damage to the
exposed neural elements through mechanical and chemical trauma. In a hope to
reduce the numerous surgical procedures, medical complications, and lifelong
disabilities associated with MMC, the proposal of prenatal closure was put forth
more than two decades ago. After promising results in animal models and some
clinical series, a randomized controlled trial, the Management of
Myelomeningocele Study (MOMS), was conducted. The MOMS trial demonstrated that
closure during the prenatal period could be performed relatively safely and can
result in significant benefit to the child. Specifically, prenatal closure
results in improved motor function, reduced hindbrain herniation, and reduced
need for a cerebral spinal fluid diversion. Long-term outcomes of the patients in
the MOMS trial continues in the MOMS 2 study as these children grow.
Additionally, investigations are underway on modifications to the open fetal MMC
closure techniques.
PMID- 28516218
TI - A high-fat diet can affect bone healing in growing rats.
AB - A high-fat diet (HFD) can have a negative effect on bone quality in young and old
people. Although bone healing in children is normally efficient, there is no
evidence that children who have a diet rich in fat have compromised bone fracture
regeneration compared with children with recommended dietary fat levels. The
purpose of the present study was to evaluate the effects of an HFD on bone
healing in growing female rats. Twenty-six postweaning female Wistar rats were
divided into two groups (13 animals per group): a standard diet (SD) group and an
HFD (with 60% of energy from fat) group. The rats received the assigned diets for
5 weeks, and in the third week they were submitted to an osteotomy procedure of
the left tibia. Body mass and feed intake were recorded during the experiment.
One day before euthanasia, an insulin tolerance test was performed. After
euthanasia, the tibiae were removed and analyzed by densitometry, mechanical
testing, histomorphometry, stereology and immunohistochemistry. An HFD caused an
adaptive response to maintain energetic balance by decreasing feed intake and
causing insulin insensitivity. There was no change in bone mineral density,
collagen amount and immunostaining for bone formation, but maximal load and
stiffness were decreased in the HFD group. In addition, bone volume had a
tendency to be higher in the SD group than in the HFD group. Compared with rats
receiving an SD, growing rats receiving an HFD for 5 weeks had similar bone
mineral density but altered mechanical properties at the osteotomy defect site.
PMID- 28516219
TI - Decreased sensory nerve excitation and bone pain associated with mouse Lewis lung
cancer in TRPV1-deficient mice.
AB - Bone pain is one of the most common and life-limiting complications of cancer
metastasis to bone. Although the mechanism of bone pain still remains poorly
understood, bone pain is evoked as a consequence of sensitization and excitation
of sensory nerves (SNs) innervating bone by noxious stimuli produced in the
microenvironment of bone metastases. We showed that bone is innervated by
calcitonin gene-related protein (CGRP)+ SNs extending from dorsal root ganglia
(DRG), the cell body of SNs, in mice. Mice intratibially injected with Lewis lung
cancer (LLC) cells showed progressive bone pain evaluated by mechanical allodynia
and flinching with increased CGRP+ SNs in bone and augmented SN excitation in DRG
as indicated by elevated numbers of pERK- and pCREB-immunoreactive neurons.
Immunohistochemical examination of LLC-injected bone revealed that the tumor
microenvironment is acidic. Bafilomycin A1, a selective inhibitor of H+ secretion
from vacuolar proton pump, significantly alleviated bone pain, indicating that
the acidic microenvironment contributes to bone pain. We then determined whether
the transient receptor potential vanilloid 1 (TRPV1), a major acid-sensing
nociceptor predominantly expressed on SNs, plays a role in bone pain by
intratibially injecting LLC cells in TRPV1-deficient mice. Bone pain and SN
excitation in the DRG and spinal dorsal horn were significantly decreased in
TRPV1 -/- mice compared with wild-type mice. Our results suggest that TRPV1
activation on SNs innervating bone by the acidic cancer microenvironment in bone
contributes to SN activation and bone pain. Targeting acid-activated TRPV1 is a
potential therapeutic approach to cancer-induced bone pain.
PMID- 28516221
TI - Small bowel obstruction due to ingestion of rubber balls.
AB - We report a case of a 10-month-old girl who presented with a 10-day history of
emesis that became bilious on the last day. The initial evaluation suggested
small bowel obstruction. An upper gastrointestinal study confirmed the normal
location of the duodenojejunal junction with normal rotation and no evidence of
midgut volvulus. Ultrasound (US) evaluation demonstrated two intraluminal lesions
that do not follow the typical features of solid or cystic lesions. Two rubber
balls were found at surgery to be responsible for the small bowel obstruction.
Foreign body ingestion is common in children, but this case demonstrates a
unusual foreign object to be ingested as well as the US appearance of this
particular foreign body.
PMID- 28516220
TI - Prevalence and factors associated with supportive care needs among newly
diagnosed Mexican breast cancer patients.
AB - PURPOSE: Mexican breast cancer patients are generally diagnosed in advanced
stages of the disease and often experience delays in cancer treatment delivery.
Currently, little is known about these patients' psychological care needs. This
study assessed levels and correlates of supportive care needs of Mexican breast
cancer patients around the time of cancer diagnosis. METHODS: One hundred seventy
three newly diagnosed Mexican breast cancer patients participated in the study.
Supportive care needs, anxiety, depression, and patients' sociodemographic and
clinical characteristics were assessed. Multiple regression analyses were used to
examine factors associated with care needs. RESULTS: Up to 44% of patients showed
unmet care needs. Health system/information needs were the most prevalent (68%),
while physical/daily living needs the least (19%). Level of depressive symptoms
was most consistently related to care needs. Patients with higher levels of
depressive symptoms had higher psychological (beta = 0.38), physical/daily living
(beta = 0.43), patient care/support (beta = 0.17), and additional unmet care
needs (beta = 0.30), than patients with lower levels of depressive symptoms.
CONCLUSIONS: This study suggests that mainly health system/information needs
arise at the time of cancer diagnosis among Mexican breast cancer patients.
Patients suffering high levels of depressive symptoms reported the highest levels
of unmet needs. Future studies should be conducted to elucidate the care needs
throughout the disease trajectory, as such information can inform health care
professionals and policy makers and lead to improvements in the organization and
provision of health care services for Mexican breast cancer patients.
PMID- 28516222
TI - Population data of 17 Y-STRs (Yfiler) from Punjabis and Kashmiris of Pakistan.
AB - Pakistan harbors 16 major ethnic groups including Punjabis (56% of total
population) and Kashmiri (6% of total population). Here, we report data of 17 Y
chromosomal short tandem repeats (Y-STRs) genotyped with the AmpFlSTR Y-filerTM
PCR Amplification kit in 94 Punjabis and 101 Kashmiris. The estimated haplotype
diversity was higher in Punjabis (0.996) than that in Kashmiris (0.983).
Furthermore, we performed population genetic analyses by including data from six
other Pakistani groups. The presented haplotype data were recently included in
the Y-Chromosome Haplotype Reference Database (YHRD) for future forensic and
other usage.
PMID- 28516225
TI - A case of bilateral keratitis caused by Providencia alcalifaciens: a rarely
encountered ocular pathogen.
AB - PURPOSE: To report a case of keratitis caused by Providencia alcalifaciens.
METHODS: A 70-year-old man presented with pain, redness, and decreased vision in
both of his eyes. On initial presentation, the visual acuity in both of his eyes
was hand motion, and slit lamp examination showed diffuse infiltrates and total
epithelial defects of the cornea, conjunctival hyperemia, and severe anterior
chamber reactions with 2-mm-height hypopyon. The results of laboratory studies
revealed elevated liver function tests, which indicated the presence of alcoholic
liver disease. RESULTS: The culture result was positive for P. alcalifaciens and
showed sensitivity to ceftazidime and amikacin but resistant to cefazolin,
gentamicin, fluoroquinolone, and ampicillin. He was treated with topical
application and intravenous injection of ceftazidime. His keratitis resolved
gradually over 3 months as the treatment dose was tapered and the treatment was
eventually discontinued. His final visual acuity was 20/200 in the right eye and
20/60 in the left eye because of the remaining central corneal opacity.
CONCLUSIONS: We report a first case of keratitis due to P. alcalifaciens in a
chronic heavy alcohol drinker. Ophthalmologists should consider this bacterium as
a potential pathogen of corneal ulceration, when clinically suspect gram-negative
bacterial keratitis especially in immunocompromised state.
PMID- 28516223
TI - Two stage revision hip arthroplasty in periprosthetic joint infection. Comparison
study: with or without the use of a spacer.
AB - PURPOSE: The aim of this study was to compare two methods of two-stage surgery
for PJI (periprosthetic joint infection) after THA (total hip arthroplasty): one
with and one without the use of an antibiotic-loaded cement spacer. METHODS: This
retrospective study was performed on 99 consecutive patients (99 hips) with a
minimum follow-up of 24 months. Patients were divided into two groups: (1) in
whom the operation was performed using a spacer, and (2) for whom a spacer was
not used. RESULTS: For the whole cohort, the results improved between pre
operative and final follow-up. Recurrence of infection was found in nine out of
98 patients (9.2%) and was not significantly different between the two groups.
Patients treated with a spacer had better functional improvement in the interim
period, but the VAS score was better in the non-spacer group. The improvement in
final function was better in the spacer group with regard to HHS, but not
according to WOMAC score or VAS at final follow-up. CONCLUSION: The resection
arthroplasty should be awarded particular consideration in cases of poor soft
tissue quality, bone stock deficiency, when complications related to spacer use
are expected or chances of new hip endoprosthesis implantation are low.
PMID- 28516226
TI - Benefit of adding digital breast tomosynthesis to digital mammography for breast
cancer screening focused on cancer characteristics: a meta-analysis.
AB - PURPOSE: We evaluated the benefit of adding digital breast tomosynthesis (DBT) to
full-field digital mammography (FFDM) compared to FFDM alone for breast cancer
detection, focusing on cancer characteristics. METHODS: We searched electronic
databases and relevant references for published studies comparing DBT plus FFDM
to FFDM alone for breast cancer screening. Pooled risk ratios (RRs) for various
pathologic findings were determined using random effects models. RESULTS: Eleven
eligible studies were included. Pooled RRs showed a greater cancer detection for
DBT plus FFDM than for FFDM alone for invasive cancer (1.327; 95% CI, 1.168
1.508), stage T1 (1.388; 95% CI, 1.137-1.695), nodal-negative (1.451; 95% CI,
1.209-1.742), all histologic grades (grade I, 1.812; grade II/III, 1.403), and
histologic types of invasive cancer (ductal, 1.437; lobular, 1.901). However,
adding DBT did not increase for detection of carcinoma in situ (1.198; 95% CI,
0.942-1.524), stage >=T2 (1.391; 95% CI, 0.895-2.163), or nodal-positive cancer
(1.336; 95% CI, 0.921-1.938). Heterogeneity among studies was not significant in
any subset analysis. CONCLUSIONS: Adding DBT to FFDM enabled detection of early
invasive breast cancer that might have been missed with FFDM alone. Knowing which
cancer characteristic DBT detects may allow it to play a complementary role in
predicting long-term patient outcomes and facilitate treatment planning.
PMID- 28516227
TI - Impairment in Mismatch Negativity but not Repetition Suppression in
Schizophrenia.
AB - Schizophrenia is characterized by impaired auditory-evoked potentials (AEPs),
mismatch negativity (MMN), and sensory gating of AEPs to repeated stimuli
(repetition suppression, RS). In the predictive modeling framework, MMN and RS
reflect encoding of prediction error and model sharpening, respectively. We
compared P50, N100, P200 RS, and pitch and duration MMN in 26 participants
diagnosed with schizophrenia (SZ) and 26 matched healthy controls (HC), and
assessed relationships between MMN, RS, and SZ diagnosis. RS was measured by
comparing responses to individual tones presented as 5-tone groups (1 kHz, 75 dB,
50 ms, 5 ms rise/fall times, 330 ms SOA), separated by a 750 ms inter-trial
interval. For MMN, the same tones were presented, with occasional pitch (1.2 kHz,
10%) or duration deviants (100 ms, 10%) interspersed. Pitch and duration MMN were
reduced in SZ (p < 0.01). There were no group differences in P50 RS, N100 RS, or
P200 RS (p's > 0.1). Importantly, although pitch and duration MMN both correlated
with RS of AEPs within the MMN time range (p's < 0.01), SZ diagnosis predicted
MMN over and above RS (p < 0.05) and shared little variance with RS in prediction
of MMN amplitude (tolerance > 0.93). We suggest that reduced MMN in SZ is related
to deficits in encoding prediction error but not repetition suppression.
PMID- 28516228
TI - Great sandeel (Hyperoplus lanceolatus) as a putative transmitter of parasite
Contracaecum osculatum (Nematoda: Anisakidae).
AB - In the Baltic Sea, the great sandeel (Hyperoplus lanceolatus), a common fish
species that inhabits sandy substrates, is an important element in the diet of
marine mammals, sea birds, and piscivorous fish. It can also act as a transmitter
of parasites to its predators, but parasitological studies on this species are
limited. We sampled great sandeels in April 2016 in two areas of the southern
Baltic Sea (SB-south of Bornholm and GG-the Gulf of Gdansk) and found parasitic
anisakid nematodes in both locations. The only one species of nematode parasites
has been detected: liver worm (Contracaecum osculatum) with average prevalence of
infection 8.96%. This is the first study to report on infection of H. lanceolatus
with anisakid nematodes in the southern Baltic Sea and our results suggest that
the great sandeel may play a role in the transmission of liver worm in the food
web of this marine environment.
PMID- 28516229
TI - Letter to the Editor concerning "The effect of total hip arthroplasty on sagittal
spinal-pelvic-leg alignment and low back pain in patients with severe hip
osteoarthritis" by W. Weng et al. Eur Spine J (2016);25(11):3608-3614.
PMID- 28516224
TI - Psychiatric behaviors associated with cytoskeletal defects in radial neuronal
migration.
AB - Normal development of the cerebral cortex is an important process for higher
brain functions, such as language, and cognitive and social functions.
Psychiatric disorders, such as schizophrenia and autism, are thought to develop
owing to various dysfunctions occurring during the development of the cerebral
cortex. Radial neuronal migration in the embryonic cerebral cortex is a complex
process, which is achieved by strict control of cytoskeletal dynamics, and
impairments in this process are suggested to cause various psychiatric disorders.
Our recent findings indicate that radial neuronal migration as well as
psychiatric behaviors is rescued by controlling microtubule stability during the
embryonic stage. In this review, we outline the relationship between psychiatric
disorders, such as schizophrenia and autism, and radial neuronal migration in the
cerebral cortex by focusing on the cytoskeleton and centrosomes. New treatment
strategies for psychiatric disorders will be discussed.
PMID- 28516230
TI - Diverse roles of Dpb2, the non-catalytic subunit of DNA polymerase epsilon.
AB - Timely progression of living cells through the cell cycle is precisely regulated.
This involves a series of phosphorylation events which are regulated by various
cyclins, activated in coordination with the cell cycle progression.
Phosphorylated proteins govern cell growth, division as well as duplication of
the genetic material and transcriptional activation of genes involved in these
processes. A subset of these tightly regulated genes, which depend on the MBF
transcription factor and are mainly involved in DNA replication and cell
division, is transiently activated at the transition from G1 to S phase. A
Saccharomyces cerevisiae mutant in the Dpb2 non-catalytic subunit of DNA
polymerase epsilon (Polepsilon) demonstrates abnormalities in transcription of
MBF-dependent genes even in normal growth conditions. It is, therefore, tempting
to speculate that Dpb2 which, as described previously, participates in the early
stages of DNA replication initiation, has an impact on the regulation of
replication-related genes expression with possible implications for genomic
stability.
PMID- 28516231
TI - Molecular evolution of type II MAGE genes from ancestral MAGED2 gene and their
phylogenetic resolution of basal mammalian clades.
AB - Type II melanoma-associated antigens (MAGE) are a subgroup of about a dozen
proteins found in various locations in the genome and expressed in normal
tissues, thus are not related to cancer as the type I MAGE genes. This gene
family exists as a single copy in non-mammals and monotremata, but found as two
copies in metatherians and occur as a diverse group in all eutherians. Our
studies suggest MAGED2 as the ancestor of this subfamily and the most likely
evolutionary history of eutherian type II MAGE genes is hereby proposed based on
synteny conservation, phylogenetic relations, genome location, homology
conservation, and the protein and gene structures. Type II genes can be divided
into two: those with 13 exons (MAGED1, MAGED2, TRO, and MAGED4) and those with
only one exon (MAGEE1, MAGEE2, MAGEF1, NSMCE3, MAGEH1, MAGEL2, and NDN) with
different evolutionary patterns. Our results suggest a need to change the gene
nomenclature to MAGE1 (the ancestral gene), currently designated as LOC103095671
and LOC100935086, in opossum and Tasmanian devil, respectively, and MAGE2 (the
duplicated one), currently designated as LOC100617402 and NDNL2, respectively, to
avoid confusion. We reconstructed the phylogenetic relationships among 23
mammalian species using the combined sequences of MAGED1, MAGED2, MAGEL2, and
NDN, because of their high divergence, and found high levels of support, being
able to resolve the phylogenetic relationships among Euarchontoglires,
Laurasiatheria, Afrotheria, and Xenarthra, as an example that small, but
phylogenetically informative sequences, can be very useful for resolving basal
mammalian clades.
PMID- 28516232
TI - [CNS metabolism in high-risk drug abuse, German version : Insights gained from 1H
and 31P MRS and PET].
AB - BACKGROUND: High-risk drug consumption is a considerable problem for public
health actors in industrialised countries. The latest trends show a market
tendency towards diversification and increasing demand for high-purity synthetic
drugs. Whilst most consumers seek medical help after cannabis use, it is high
risk drugs like cocaine, heroin and amphetamines that account for most of the
1000 drug-related deaths that occur in Germany every year. PURPOSE: This article
presents the most prominent in vivo cerebral metabolic information in cocaine,
heroin and methamphetamine users provided by MRI spectroscopy and PET imaging.
MATERIALS AND METHODS: We reviewed the literature reporting neuroimaging studies
of in vivo metabolic data for methamphetamine, cocaine and heroin consumption
published up to March 2017. The search was conducted using PubMed with the
following key words: methamphetamine, cocaine, heroin, MR spectroscopy, PET.
CONCLUSION: MRI and PET are indispensable tools in gauging brain metabolic
response to illegal drug abuse. Future breakthroughs in this field will most
likely come from the investigation of novel neurotransmitter systems in PET and
imaging phosphorus and carbon metabolites in MRI.
PMID- 28516233
TI - Medical Image Data and Datasets in the Era of Machine Learning-Whitepaper from
the 2016 C-MIMI Meeting Dataset Session.
AB - At the first annual Conference on Machine Intelligence in Medical Imaging (C
MIMI), held in September 2016, a conference session on medical image data and
datasets for machine learning identified multiple issues. The common theme from
attendees was that everyone participating in medical image evaluation with
machine learning is data starved. There is an urgent need to find better ways to
collect, annotate, and reuse medical imaging data. Unique domain issues with
medical image datasets require further study, development, and dissemination of
best practices and standards, and a coordinated effort among medical imaging
domain experts, medical imaging informaticists, government and industry data
scientists, and interested commercial, academic, and government entities. High
level attributes of reusable medical image datasets suitable to train, test,
validate, verify, and regulate ML products should be better described. NIH and
other government agencies should promote and, where applicable, enforce, access
to medical image datasets. We should improve communication among medical imaging
domain experts, medical imaging informaticists, academic clinical and basic
science researchers, government and industry data scientists, and interested
commercial entities.
PMID- 28516235
TI - Clinical, imaging and genotypical features of three deceased and five surviving
cases with ADA2 deficiency.
AB - Deficiency of adenosine deaminase type 2 (DADA2) is a rare form of
autoinflammatory disorder with limited reported cases. In this paper, we have
presented the clinico-immunological, radiological and genetic characteristics of
five surviving and three deceased childhood-onset DADA2 patients. We aimed to
compare surviving and deceased patients in terms of clinical features and
treatment modalities. Moreover, we have evaluated the causes of death in our
DADA2 subjects together with the previously reported cases. Demographic features,
clinical characteristics, imaging findings, mutations and pharmacological
treatments of DADA2 subjects were noted from patient records of pediatric and
adult rheumatology clinics in a retrospective and longitudinal nature. Eight
patients from seven families were enrolled. While five of them were surviving,
three of them had died due to various reasons. Median age of the patients at
disease onset and diagnosis was 7 years (range 0.5-13 years) and 14 years (range
5-27 years), respectively. The main clinical manifestations were cutaneous
findings (7/8), recurrent low-grade fever (6/8), neurological involvement (6/8)
and gastrointestinal involvement (5/8). All patients had increased acute phase
reactants at presentation and also during the disease flares. Until the diagnosis
of DADA2 was confirmed, five patients have been followed-up with the diagnosis of
PAN: two patients both with PAN and FMF, and one patient with CAPS and
vasculitis. Demographic, clinical, neurological features and genetic mutations
did not differ in surviving and deceased DADA2 patients. Deceased and surviving
subjects differed in terms of treatment modalities after the diagnosis of DADA2.
Anti-TNF alpha treatment has been initiated in five surviving patients as soon as
the diagnosis of DADA2 was established. However, three patients who have died
were not able to use sufficient doses of anti-TNF alpha treatment; in one case
due to reluctance of patient and in two cases due to establishment of the
definite diagnosis by genetic analysis at the same time with the last fatal DADA2
episode. Despite limited number of patients, this case series for the first time
compares the phenotypic, genotypic and medication differences between surviving
and deceased DADA2 patients. Anti-TNF alpha treatment seems to be efficient and
lifesaving in DADA2 patients.
PMID- 28516234
TI - Assessing long-term return to play after hip arthroscopy in football players
evaluating risk factors for good prognosis.
AB - PURPOSE: Groin pain is the third most common disease in football players and has
often been associated with hip pathology such as femoroacetabular impingement and
labral lesions. Hip arthroscopy offers possibilities of function restoration via
minimally invasive procedures. The aim of this study is to evaluate professional
football player's injuries and their return to play after hip arthroscopy for FAI
and labral injuries. METHODS: Patients that underwent hip arthroscopy between
2009 and 2014 were selected retrospectively. From this population, only
professional soccer players competing at national level were included (Tegner
10). Arthroscopic surgery was proposed in patients with persistent pain. All
patients were assessed for VAS score preoperatively and at 3, 6, 12 and 24 months
post-op. HOS (sport and DLA) and mHHS tests were performed at the same time
periods. RESULTS: All patients were men with a mean age of 26.5 +/- 7.1 years
old. Preoperative VAS (7.4 +/- 1.3), HOS ADL (67.7 +/- 5.5), HOS sport (37.6 +/-
18.7) and mHHS (72.5 +/- 8.8) showed improved scores during long-term follow-up.
Time to return to play was 10.8 months (SD +/- 4.3), with range between 4 and 20
months. Mean follow-up was 45.4 +/- 15.6 months (range from 26 to 72 months). No
differences were observed between non-active and active patients at final follow
up with respect to chondral lesions, but significant differences were observed
with reference to management of the labrum (p = 0.031), where a higher rate of
labrectomies existed among inactive patients and a higher rate of suture among
active patients. CONCLUSIONS: Hip arthroscopy is a safe procedure with very good
return to play results, but for optimized return to football one should consider
patient age at the time of surgery, the condition of the labrum and low scores on
the Harris Hip Score (mHHS) and HOS (sport version) as predictive factors for
poor prognosis. Level of evidence IV.
PMID- 28516236
TI - Identification of patients at risk of non-adherence to oral antirheumatic drugs
in rheumatoid arthritis using the Compliance Questionnaire in Rheumatology: an
ARCO sub-study.
AB - The ARCO study (Study on Adherence of Rheumatoid Arthritis patients to
SubCutaneous and Oral Drugs), a multicenter, non-interventional retrospective
study, was primarily designed to assess the percentage of patients [aged >=18
years with an established rheumatoid arthritis (RA) diagnosis] with non-adherence
to prescribed subcutaneous biologicals. This paper reports data for the secondary
objective from a subset of patients, namely to evaluate non-adherence to
prescribed oral antirheumatic drugs in RA patients in Spain using the validated
Compliance Questionnaire Rheumatology (CQR). Patients also completed the Morisky
Green Medication Adherence Questionnaire, Beliefs about Medicines Questionnaire,
and a questionnaire (developed and validated in Spain) on patient satisfaction
with RA treatment and preferences. A total of 271 patients (76.7% females; mean
age 55.6 years) were being treated with oral drugs for RA, of which 234 completed
the CQR questionnaire. Non-adherence was reported in 49/234 (20.9%) patients. The
proportion of non-adherence in younger patients (aged <=48 years; 37.5%) was
double that recorded in patients aged >48 years (p = 0.006). Patients with a
perception of lower efficacy also had a higher risk of non-adherence (p = 0.012).
Multivariable analysis showed that younger age and male gender were independently
associated with risk of non-adherence. There was only slight agreement between
the CQR and Morisky-Green assessment tools (kappa coefficient = 0.186), possibly
reflecting the fact that both questionnaires measure slightly different aspects
of medication adherence. In conclusion, one out of five RA patients was
identified as at risk for non-adherence with the CQR, and this was more frequent
in younger patients and in males.
PMID- 28516239
TI - Regulation of endogenous brakes to kidney fibrosis: turning the view upside down.
PMID- 28516238
TI - Foot pain severity is associated with the ratio of visceral to subcutaneous fat
mass, fat-mass index and depression in women.
AB - Body composition and poor mental health are risk factors for developing foot
pain, but the role of different fat deposits and psychological features related
to chronic pain are not well understood. The aim of this study was to investigate
the association between body composition, psychological health and foot pain.
Eighty-eight women participated in this study: 44 with chronic, disabling foot
pain (mean age 55.3 SD 7.0 years, BMI 29.5 SD 6.7 kg/m2), and 44 age and BMI
matched controls. Disabling foot pain was determined from the functional
limitation domain of the Manchester Foot Pain and Disability Index. Body
composition was measured using dual X-ray absorptiometry and psychological health
(catastrophisation, central sensitisation and depression) was measured using
three validated questionnaires. Between-group analyses found that foot pain was
not significantly associated with body composition variables, but was
significantly associated with all psychological health measures (P < 0.001
0.047). Within-group analyses found that the severity of foot pain was
significantly correlated with body composition measures: fat mass (total,
android, gynoid, and visceral), fat-mass ratios [visceral/subcutaneous (VAT/SAT),
visceral/android], fat-mass index (FMI), and depression. In multivariable
analysis, VAT/SAT (beta 1.27, 95% CI 0.28-2.27), FMI (beta 0.14, 95% CI 0.02
0.25) and depression (beta 0.06, 95% CI 0.00-0.12) were independently associated
with foot pain severity. Psychological health, not body composition, was
associated with prevalent foot pain. For women with foot pain, VAT/SAT, FMI and
depression were associated with severity. Further work is needed to determine if
a reduction in fat mass reduces the severity of foot pain.
PMID- 28516237
TI - Rheumatoid factor positivity increases all-cause and cancer mortality: a cohort
study.
AB - The aim of this study was to determine whether rheumatoid factor (RF) is
associated with mortality from all-cause, cardiovascular disease (CVD), and
cancer in the healthy adults. We recruited South Korean health check-up examinees
without rheumatoid arthritis (RA). A cohort study was performed in 295,837
participants presumably free of osteoarthritis or RA, and who had undergone
health screening between 2002 and 2012 and been followed up to determine the risk
of all-cause, CVD, and cancer-specific mortality with respect to the presence or
titer of RF. To determine whether the participants were deceased, we used
National Death Index death certificates. The prevalence of RF positivity (>=20
IU/mL) was 4.4%. During 1,447,403 person-years of follow-up, 1402 participants
died. Comparing subjects negative for RF with those positive for RF, the
multivariable adjusted hazard ratio (HR; 95% CI) for all-cause and cancer
mortality in subjects with RF-positivity was 1.50 (1.19-1.90) and 1.56 (1.12
2.16), respectively. Also, all-cause and cancer mortality risk was significantly
greater in subjects with an RF titer greater than 100 IU/mL than in those with RF
negativity (HR = 2.68, 95% CI = 1.72-4.19; HR = 2.89, 95% CI = 1.58-5.28,
respectively) after adjusting for multiple confounders. However, the HR for
cardiovascular mortality was not higher in subjects with RF positivity than in
those with RF negativity (HR = 0.98, 95% CI = 0.45-2.11). In Korean healthy
adults, presumably without RA, RF was associated with a greater risk of all-cause
and cancer mortality.
PMID- 28516242
TI - Defining and understanding the relationship between professional identity and
interprofessional responsibility: implications for educating health and social
care students.
AB - This paper is concerned with exploring the relationship between perceptions of
professional identities, interprofessional education (IPE) and collaborative
practice. It seeks to introduce the concept of interprofessional responsibility
as both a shift in the way in which to conceptualise the professional identity of
Health and Social Care (H&SC) staff and as a new set of practices that help to
inform the way in which students are prepared for collaborative working. The
presented research, undertaken as part of a Ph.D. study, is based upon semi
structured interviews (n = 33) with H&SC staff who were recruited from both the
United Kingdom (UK) Health Service and UK universities. Drawing upon thematic
analysis of the data, the results of the research identified that previous
conceptualisations of professional identity aligned to a whole profession do not
relate to the way in which professionals perceive their identities. Senior
professionals claimed to be more comfortable with their own professional
identity, and with working across professional boundaries, than junior
colleagues. Academic staff also identified that much IPE currently taught in
universities serves the purpose of box-ticking rather than being delivered in
meaningful way. It is proposed that the findings have implications for the way in
which IPE is currently taught, and that adoption of the proposed concept of
'interprofessional responsibility' may help address some of the concerns these
findings raise.
PMID- 28516240
TI - In vivo PET imaging of neuroinflammation in Alzheimer's disease.
AB - Increasing evidence suggests that neuroinflammation contributes to the
pathophysiology of many neurodegenerative diseases, especially Alzheimer's
disease (AD). Molecular imaging by PET may be a useful tool to assess
neuroinflammation in vivo, thus helping to decipher the complex role of
inflammatory processes in the pathophysiology of neurodegenerative diseases and
providing a potential means of monitoring the effect of new therapeutic
approaches. For this objective, the main target of PET studies is the 18 kDa
translocator protein (TSPO), as it is overexpressed by activated microglia. In
the present review, we describe the most widely used PET tracers targeting the
TSPO, the methodological issues in tracer quantification and summarize the
results obtained by TSPO PET imaging in AD, as well as in neurodegenerative
disorders associated with AD, in psychiatric disorders and ageing. We also
briefly describe alternative PET targets and imaging modalities to study
neuroinflammation. Lastly, we question the meaning of PET imaging data in the
context of a highly complex and multifaceted role of neuroinflammation in
neurodegenerative diseases. This overview leads to the conclusion that PET
imaging of neuroinflammation is a promising way of deciphering the enigma of the
pathophysiology of AD and of monitoring the effect of new therapies.
PMID- 28516243
TI - Clinical characteristics, risk factors and long-term outcome of 114 patients with
folliculotropic mycosis fungoides.
AB - Folliculotropic mycosis fungoides (FMF) is a distinct variant of mycosis
fungoides (MF) where atypical T-cells invade the hair follicles. The objective
was to assess the clinical features, risk factors for progression, long-term
outcome and response to treatment modalities in a large cohort of FMF patients.
We, therefore, conducted a single-center retrospective study, reviewing 114
patients with FMF seen from 1987 to 2015 at the cutaneous T-cell lymphoma clinic
of the MD Anderson Cancer Center. The mean age at diagnosis of FMF was 57.1 +/-
13.5 years. The male to female ratio was 1.2:1. MF stage IA (n = 50, 43.9%) was
the most common diagnosed stage, followed equally by stages IB and IIB (n = 23,
20.2%, respectively). Eighty-six patients (75.4%) suffered from pruritus.
Concomitant hair loss was observed in 37 (32.5%) subjects. The median number of
different treatment modalities used per patient was 4 (range 1-12). Low-dose
radiation was beneficial in clearing therapy refractory lesions. The overall
survival was influenced by several factors, including advanced age (>65), late
stages and the presence of large cell transformation (LCT). Thirty-three of 113
patients (29.2%) progressed to more advanced stages and 26 (23.0%) died, with the
cause of death being MF in 11 (9.7%) subjects. In conclusion, patients with FMF
have a worse overall 10-year survival rate compared with other MF variants.
Several factors, including stage, advanced age and the presence of LCT impact
survival. Multiple different treatment approaches may be needed to achieve a good
clinical response and to prevent disease progression.
PMID- 28516241
TI - Innate immunity in Alzheimer's disease: the relevance of animal models?
AB - The mouse is one of the organisms most widely used as an animal model in
biomedical research, due to the particular ease with which it can be handled and
reproduced in laboratory. As a member of the mammalian class, mice share with
humans many features regarding metabolic pathways, cell morphology and anatomy.
However, important biological differences between mice and humans exist and must
be taken into consideration when interpreting research results, to properly
translate evidence from experimental studies into information that can be useful
for human disease prevention and/or treatment. With respect to Alzheimer's
disease (AD), much of the experimental information currently known about this
disease has been gathered from studies using mainly mice as models. Therefore, it
is notably important to fully characterise the differences between mice and
humans regarding important aspects of the disease. It is now widely known that
inflammation plays an important role in the development of AD, a role that is not
only a response to the surrounding pathological environment, but rather seems to
be strongly implicated in the aetiology of the disease as indicated by the
genetic studies. This review highlights relevant differences in inflammation and
in microglia, the innate immune cell of the brain, between mice and humans
regarding genetics and morphology in normal ageing, and the relationship of
microglia with AD-like pathology, the inflammatory profile, and cognition. We
conclude that some noteworthy differences exist between mice and humans regarding
microglial characteristics, in distribution, gene expression, and states of
activation. This may have repercussions in the way that transgenic mice respond
to, and influence, the AD-like pathology. However, despite these differences,
human and mouse microglia also show similarities in morphology and behaviour,
such that the mouse is a suitable model for studying the role of microglia, as
long as these differences are taken into consideration when delineating new
strategies to approach the study of neurodegenerative diseases.
PMID- 28516244
TI - A comparison of basilar artery diameters measured by T2WI and TOF MR angiography.
AB - PURPOSE: The purpose of our study is to compare basilar artery diameters (BAD)
measured by T2WI to diameters measured by TOF MR angiography (MRA). By doing
this, we hope to understand how compatible these two methodologies are with each
other. METHODS: We used data from 100 patients (59 females, 41 males) who
underwent a session of both T2W MRI and TOF MRA at the same time (ages between 18
and 83). We measured BAD by both T2WI and TOF MRA in three different levels. We
then compared these diameters measured by two different methodologies to each
other. RESULTS: In an area between the vertebrobasilar junction and posterior
cerebral artery, all data measured by T2WI and TOF MRA in three different levels
were analyzed. Average diameters measured by T2WI and TOF MRA turned out to be
79.5% correlated with each other. As a result of our mathematical model that we
came up with through regression analysis, we calculated that measurements taken
by T2WI on mid-pontine levels could predict TOF MRA measures with 78.3% accuracy.
In T2WI and TOF MRA, average diameters measured were 2.982 +/- 0.4717 and 3.205
+/- 0.4281 mm, respectively. Statistical analyses showed that images measured by
T2W series were significantly smaller than those measured by TOF MRA (p < 0.05).
CONCLUSION: Our study showed that BAD measured by T2WI were smaller than those
measured by TOF MRA. We think that it will be beneficial to refer our results to
avoid T2WI and TOF MRA mismatch when evaluating BAD.
PMID- 28516245
TI - Municipal solid waste-derived biochar for the removal of benzene from landfill
leachate.
AB - The potential of biochar, produced from fibrous organic fractions of municipal
solid waste (MSW), for remediation of benzene, one of the frequently found toxic
volatile organic compounds in landfill leachate, was investigated in this study
based on various environmental conditions such as varying pH, benzene
concentration, temperature and time. At the same time, landfill leachate quality
parameters were assessed at two different dump sites in Sri Lanka: Gohagoda and
Kurunegala. MSW biochar (MSW-BC) was produced by slow temperature pyrolysis at
450 degrees C, and the physiochemical characteristics of the MSW-BC were
characterized. All the leachate samples from the MSW dump sites exceeded the
World Health Organization permissible level for benzene (5 ug/L) in water.
Removal of benzene was increased with increasing pH, with the highest removal
observed at ~pH 9. The maximum adsorption capacity of 576 ug/g was reported at
room temperature (~25 degrees C). Both Freundlich and Langmuir models fitted
best with the equilibrium isotherm data, suggesting the involvement of both
physisorption and chemisorption mechanisms. Thermodynamic data indicated the
feasibility of benzene adsorption and its high favorability at higher
temperatures. The values of [Formula: see text] suggested physical interactions
between sorbate and sorbent, whereas kinetic data implied a significant
contribution of chemisorption. Results obtained from FTIR provided clear evidence
of the involvement of functional groups in biochar for benzene adsorption. This
study suggests that MSW biochar could be a possible remedy for benzene removal
from landfill leachate and at the same time MSW can be a potential source to
produce biochar which acts as a prospective material to remediate its pollutants
while reducing the volume of waste.
PMID- 28516247
TI - Genetic heterogeneity among slow acetylator N-acetyltransferase 2 phenotypes in
cryopreserved human hepatocytes.
AB - Genetic polymorphisms in human N-acetyltransferase 2 (NAT2) modify the metabolism
of numerous drugs and carcinogens. These genetic polymorphisms modify both drug
efficacy and toxicity and cancer risk associated with carcinogen exposure.
Previous studies have suggested phenotypic heterogeneity among different NAT2
slow acetylator genotypes. NAT2 phenotype was investigated in vitro and in situ
in samples of human hepatocytes obtained from various NAT2 slow and intermediate
NAT2 acetylator genotypes. NAT2 gene dose response (NAT2*5B/*5B > NAT2*5B/*6A >
NAT2*6A/*6A) was observed towards the N-acetylation of the NAT2-specific drug
sulfamethazine by human hepatocytes both in vitro and in situ. N-acetylation of 4
aminobiphenyl, an arylamine carcinogen substrate for both N-acetyltransferase 1
and NAT2, showed the same trend both in vitro and in situ although the
differences were not significant (p > 0.05). The N-acetylation of the N
acetyltransferase 1-specific substrate p-aminobenzoic acid did not follow this
trend. In comparisons of NAT2 intermediate acetylator genotypes, differences in N
acetylation between NAT2*4/*5B and NAT2*4/*6B hepatocytes were not observed in
vitro or in situ towards any of these substrates. These results further support
phenotypic heterogeneity among NAT2 slow acetylator genotypes, consistent with
differential risks of drug failure or toxicity and cancer associated with
carcinogen exposure.
PMID- 28516248
TI - Environmental toxicants, incidence of degenerative diseases, and therapies from
the epigenetic point of view.
AB - Epigenotoxicology is an emerging field of study that investigates the non
genotoxic epigenetic effects of environmental toxicants resulting in alteration
of normal gene expression and disruption of cell function. Recent findings on the
role of toxicant-induced epigenetic modifications in the development of
degenerative diseases have opened up a promising research direction to explore
epigenetic therapy approaches and related prognostic biomarkers. In this review,
we presented comprehensive data on epigenetic alterations identified in various
diseases, including cancer, autoimmune disorders, pulmonary conditions as well as
cardiovascular, gastrointestinal and bone disease. Although data on abnormalities
of DNA methylation and their role in the development of diseases are abundant,
less is known about the impact of histone modifications and microRNA expressions.
Further, we discussed the effects of selected common environmental toxicants on
epigenetic modifications and their association with particular abnormalities. A
number of different environmental toxicants have been identified for their role
in aberrant DNA methylation, histone modifications, and microRNA expression. Such
epigenetic effects were shown to be tissue-type specific and highly associated
with the level and duration of exposure. Finally, we described present and future
therapeutic strategies, including medicines and dietary compounds for combating
the toxicant-induced epigenetic alterations. There are currently seven histone
deacetylase inhibitors and two DNA methyltransferase inhibitors approved for
clinical use and many other promising candidates are in preclinical and clinical
testing. Dietary compounds are thought to be the effective and safe strategies
for treating and prevention of epigenetic pathophysiological conditions. Still
more concentrated epigenetic researches are required for evaluation of chemical
toxicity and identifying the causal association between key epigenetic alteration
and disease.
PMID- 28516249
TI - [A 67-year-old man with fever, night sweat and ascites].
AB - A 67-year-old man presented with fever, night sweat and abdominal complaints for
about 4 weeks. Ultrasound and a computed tomography scan showed distinct ascites
as the main finding, presenting as exsudate with predominating lymphoid cells.
Because of long-term immunosuppressive therapy with the tumor necrosis factor
(TNF)-alpha inhibitor golimumab for psoriasis, the suspicion for a possible
tuberculous peritonitis arose. This was confirmed with an enzyme-linked
immunospot assay, a high level of adenosine deaminase in the ascites and a
peritoneum which was studded with multiple whitish nodules, corresponding to
granulomas with giant cells. With a standard antituberculous regimen the symptoms
were quickly relieved and finally complete restitution was achieved.
PMID- 28516246
TI - Aspergillus Species in Bronchiectasis: Challenges in the Cystic Fibrosis and Non
cystic Fibrosis Airways.
AB - Bronchiectasis is a chronic irreversible airway abnormality associated with
infectious agents that either cause or superinfect the airways. While the role of
bacteria is well studied, much remains to be determined about fungi in both
cystic fibrosis- and non-cystic fibrosis-related bronchiectasis. The airway is
constantly exposed to inhaled ambient moulds of which Aspergillus represent the
most ubiquitous. In a normal healthy host, this situation is of little
consequence. The presence of anatomical or immunological abnormalities such as
those in bronchiectasis leads to a range of fungal-related pathologies from
asymptomatic airway colonization to fungal sensitization, allergic
bronchopulmonary aspergillosis or chronic pulmonary aspergillosis. These entities
are difficult to recognize, diagnose and treat due in part to a lack of validated
biomarkers. Our true understanding of the complex relationships that regulate
fungal-host interactions is still in its infancy and, several questions remain.
This includes if fungal epidemiology in bronchiectasis is uniform across
countries, and to what extent immunopathological mechanisms-related to fungal
airway infections-occurs in different disease states. Specific triggers to
allergic or infectious responses to Aspergillus require further exploration. How
transition occurs between allergic and invasive phenotypes and their respective
biomarkers is also important. Whether anti-fungal treatment is warranted in all
cases and what the optimal management strategy is, particularly when treatment
should commence and its expected duration remains unclear. Further research is
clearly necessary and should be prioritized to better understand the clinical
effects and impact of Aspergillus in the setting of bronchiectasis.
PMID- 28516250
TI - [Choosing wisely recommendations in angiology].
AB - BACKGROUND: The Choosing wisely initiative addresses measures of high medical
impact which are frequently not appropriately performed according to expert
opinion. OBJECTIVE: To increase the quality of indications by providing
supportive information on diagnostic and therapeutic measures in the field of
angiology. MATERIALS AND METHODS: As part of the Choosing wisely initiative, the
German Society of Angiology has constructed five positive recommendations on
underused measures and five negative recommendations concerning those possibly
overused. The recommendations were validated by the twelve professional societies
of the German Society of Internal Medicine in a consensus conference. RESULTS AND
DISCUSSION: The recommendations cover a broad spectrum of diagnostic and
therapeutic modalities, such as the role of ultrasound examinations in vascular
diseases, screening for abdominal aortic aneurysms, diagnosis and therapy of
peripheral artery disease (PAD), investigation of chronic ulcers, therapy of
varicosis, and finally, the problems associated with using anticoagulants in PAD
or thrombosis. By discussing the evidence, we aim to demonstrate that not all
medically possible measures are actually appropriate in every situation.
PMID- 28516251
TI - [Severe hypertriglyceridemia : Diagnostics and new treatment principles].
AB - Severe hypertriglyceridemia is defined at a plasma triglyceride (TG)
concentration of >885 mg/dl and may result - in particular when clinical symptoms
appear before the age of 40 - from "large variant" mutations in genes which
influence the function of the lipoprotein lipase (LPL). For diagnosis, secondary
factors have to be excluded and treated before further genetic tests are
considered. Typical symptoms in almost all patients are recurrent, sometimes
severe abdominal pain attacks, which can result in acute pancreatitis, the most
important, sometimes life-threatening complication. To minimize the risk of
severe pancreatitis, the aim is to maintain the plasma TG concentration <1000
mg/dl. Other clinical manifestations which can occur and are reversible are
eruptive xanthomas, lipemia retinalis, hepatosplenomegaly, dyspnea syndrome, and
impaired neurocognitive function. The hyperviscosity syndrome caused by
chylomicronemia is seen as the underlying reason for some of the symptoms.
Patients with mild-to-moderate hypertriglyceridemia have an increased
cardiovascular risk. To lower this is the primary treatment goal here. Treatment
mainly consists of a life-long, strict fat- and carbohydrate-restricted diet and
the abstention from alcohol. Omega-3-Fatty acids and fibrates can be used to
lower plasma TG levels. Recently, new gene therapy approaches for LPL-deficient
patients have become available in Germany.
PMID- 28516252
TI - Chronic eccentric arm cycling improves maximum upper-body strength and power.
AB - INTRODUCTION: Eccentric leg cycling (cycle ergometry adapted to impose muscle
lengthening contractions) offers an effective exercise for restoring lower-body
muscular function, maintaining health, and improving performance in clinical and
athletic populations. PURPOSE: We extended this model to the upper body and
evaluated the effectiveness of a 7-week eccentric arm cycling (ECCarm)
intervention to improve upper-body muscular function. We also explored whether
ECCarm would alter arterial function. METHODS: Participants performed ECCarm (n =
9) or concentric arm cycling (CONarm; n = 8) 3*/week while training intensity
increased (5-20 min, 60-70% upper-body peak heart rate). Maximum elbow extensor
strength, upper-body concentric power, and peripheral and central arterial
stiffness were assessed before and after training. RESULTS: During training,
heart rates and perceived exertion did not differ between groups (~68% upper-body
peak heart rate, ~12 Borg units, both P > 0.05), whereas power during ECCarm was
~2* that for CONarm (122 +/- 43 vs. 59 +/- 20 W, P < 0.01). Muscle soreness for
ECCarm was greater than CONarm (P = 0.02), however, soreness was minimal for both
groups (<0.50 cm). Following training, ECCarm exhibited greater changes in elbow
extensor strength (16 +/- 10 vs. 1 +/- 9%, P = 0.01) and upper-body power (6 +/-
8 vs. -3 +/- 7%, P < 0.01) compared to CONarm. Peripheral and central arterial
stiffness did not change for either group (both P > 0.05). CONCLUSION: Upper-body
eccentric exercise improved dynamic muscular function while training at low
exertion levels. Results occurred with minimal soreness and without compromising
arterial function. ECCarm findings parallel eccentric leg cycling findings and
indicate that eccentric cycle ergometry offers a robust model for enhancing upper
body muscular function. ECCarm could have applications in rehabilitation and
sport training.
PMID- 28516254
TI - Use of Muscular Cholinesterase of Astyanax bifasciatus (Teleostei, Characidae) as
a Biomarker in Biomonitoring of Rural Streams.
AB - Cholinesterase (ChE) activity was measured in Astyanax bifasciatus maintained in
controlled conditions. Muscle ChE activity of individuals collected in field
conditions in two seasons was compared among specimens collected in seven streams
(forest and rural) of the lower Iguacu river basin in association with physical,
chemical, pesticides and biological factors. Significant differences in muscle
ChE activity between control fish and fish collected in streams in both seasons
were found, with higher activity in natural conditions. This the first time that
differences in muscle ChE activity have been found among fish collected from
different streams, suggesting synergism among multiple factors (e.g. temperature,
pH, animal weight) and ecological attributes (richness and abundance) as
influencing the variation in biomarkers. It is necessary to evaluate the quality
of aquatic environments for a more accurate biomonitoring approach.
PMID- 28516253
TI - Comparison of the effects of three different Baccaurea angulata whole fruit juice
doses on plasma, aorta and liver MDA levels, antioxidant enzymes and total
antioxidant capacity.
AB - PURPOSE: Baccaurea angulata (common names: belimbing dayak or belimbing hutan) is
a Malaysian underutilized fruit. The preliminary work on B. angulata fruit juice
showed that it possesses antioxidant properties. Therefore, further work is
needed to confirm the efficacy and proper dosage of B. angulata as a potential
natural antioxidant. The present study was thus carried out to compare the
effects of three different B. angulata whole fruit (WF) juice doses administered
at nutritional doses of 0.50, 1.00 and 1.50 ml/kg/day on plasma, aorta and liver
malondialdehyde (MDA) levels, antioxidant enzymes (superoxide dismutase,
glutathione peroxidase and catalase) as well as total antioxidant capacity in
rabbits fed high-cholesterol diet. METHODS: Thirty-five male rabbits of New
Zealand strain were randomly assigned to seven groups. For 12 weeks, group CH was
fed 1% cholesterol diet only; group C1 was fed 1% cholesterol diet and 0.50
ml/kg/day B. angulata WF juice; group C2 was fed 1% cholesterol diet and 1.00
ml/kg/day B. angulata WF juice; group C3 was fed 1% cholesterol diet and 1.50
ml/kg/day B. angulata WF juice; group N was fed standard pellet only; group N1
was fed standard pellet and 0.50 ml/kg/day B. angulata WF juice; and group N2 was
fed standard pellet and 1.00 ml/kg/day B. angulata WF juice. RESULTS: The three
doses reduced the formation of MDA and enhanced the expression of endogenous
antioxidant enzymes. The highest dose used (1.50 ml/kg/day) was, however, seen as
the most potent. CONCLUSION: Higher doses of B. angulata juice exerted better
antioxidant activity.
PMID- 28516255
TI - Water Quality Interaction with Alkaline Phosphatase in the Ganga River:
Implications for River Health.
AB - Carbon, nitrogen and phosphorus inputs through atmospheric deposition, surface
runoff and point sources were measured in the Ganga River along a gradient of
increasing human pressure. Productivity variables (chlorophyll a, gross primary
productivity, biogenic silica and autotrophic index) and heterotrophy
(respiration, substrate induced respiration, biological oxygen demand and
fluorescein diacetate hydrolysis) showed positive relationships with these
inputs. Alkaline phosphatase (AP), however, showed an opposite trend. Because AP
is negatively influenced by available P, and eutrophy generates a feedback on P
fertilization, the study implies that the alkaline phosphatase can be used as a
high quality criterion for assessing river health.
PMID- 28516257
TI - [Plant-derived contaminants in food : Occurrence, effects and risk assessment].
AB - Among the various contaminants, the group of natural plant-derived substances in
the modern food chain has been generating increasing concern in recent years. The
adverse effects encountered may be diverse and pose risks of acute, subchronic or
chronic toxicity. The underlying mechanisms of toxicity may be thresholded or be
based on interactions with DNA, as for genotoxic carcinogens, for which the
existence of a threshold cannot be assumed. This article gives an overview of the
major plant-derived contaminants of present concern in the modern food chain and
describes their mode of action and adverse effects.
PMID- 28516256
TI - [Skin diseases associated with environmental factors].
AB - BACKGROUND: Multiple environmental exposures may derange the regulatory and
repair mechanisms of the skin and lead to dermatological disease. OBJECTIVES:
Provide an overview of non-allergic skin diseases associated with environmental
factors. MATERIALS AND METHODS: Review of current scientific evidence for
associations of non-allergic skin diseases with environmental exposures:
irritation, chemicals, infection, UV-radiation, temperature. RESULTS:
Predisposition (constitution e. g. for atopic dermatitis, psoriasis and filaggrin
gene mutations) and exposure (environment) are crucial for disease development or
maintenance of health in an individual. Specific chemical and contagious agents
lead to characteristic skin diseases (e. g. halogen acne) which under certain
conditions may be recognized as occupational disease. The most frequent cause for
irritant contact dermatitis is water (wet work). Natural optical radiation of
different wavelength may cause light-induced inflammatory skin diseases.
Phototoxic reactions due to psoralens, furocoumarins and drugs are frequent. The
polymorphous light eruption is not an exogenous delayed type allergy, but seems
to be a reaction against a UV-induced neoantigen of the skin. UVB exhibits direct
mutagenic effects on DNA. Sun exposure and defective DNA-repair mechanisms are
risk factors for skin tumors. Heat/cold exposure under specific conditions also
triggers skin diseases (primary: congelations, frostbite, heat burn, scalding,
chronic-inducible urticaria; secondary: deterioration of preexisting inflammatory
diseases (e. g. systemic sclerosis)). CONCLUSIONS: To keep the skin healthy, an
early identification and elimination of harmful environmental factors and
treatment of early disease stages is necessary. This requires strategies of
environmental prevention and behavioral prevention, as well as global action (e.
g. with regard to increasing incidence of skin cancer).
PMID- 28516258
TI - [Biomarkers of internal exposure to toxicologically relevant contaminants in
food].
AB - The assessment of health risks resulting from the intake of genotoxic carcinogens
in food depends essentially on a valid exposure assessment. The reliability of
the external exposure estimation is restricted by various factors, e. g.
inaccurate data from dietary protocols and variations of food contaminant
contents. As an alternative, the individual internal exposure to genotoxic
substances may be described by specific biomarkers in different matrices. For
example, mercapturic acids formed after glutathione conjugation of electrophilic
metabolites can be detected in the urine. This typically reflects the exposure to
the parent compound over a period of one to two days. The determination of
adducts in the blood proteins serum albumin (SA) and hemoglobin (Hb) allows for
conclusions to be drawn about the external exposure within the last three weeks
(SA) or within the last four months (Hb). Protein adducts are used routinely in
occupational medicine as biomarkers of internal exposure to substances in the
ambient air of the workplace. The availability of increasingly sensitive
analytical techniques also makes it possible to detect numerous adducts in
proteins from human blood samples that are formed after the continuous intake of
very small doses of toxic substances from foods. Here, we present the current
state of science exemplified by protein adducts of the food contaminants
acrylamide, aflatoxin B1 and glycidol. The biomarker can be used in the future to
investigate previously unknown relationships between internal exposure and
disease incidences.
PMID- 28516259
TI - [Poisoning caused by marine biotoxins].
AB - This paper presents a short summary of the knowledge on marine biotoxins. As
toxins are known for their acute effects, they have been classified here
according to the effects they cause in acute human poisoning incidents. Toxins
may thus be distinguished into those that affect the nervous system (paralytic
and other neurotoxins), memory (amnesic poisons), and the digestive system
(diarrhetic toxins). Furthermore, newly emerging toxins, such as ciguatoxins or
shark toxins, and factors that lead to the introduction of toxins in new areas,
are presented. Relevant suggestions for further reading are given.
PMID- 28516260
TI - [Dietary exposure assessment of substances in foods : The BfR MEAL study - the
first German total diet study].
AB - The dietary exposure of a population to chemical substances is estimated based on
representative consumption data and data on the occurrence of substances in
foods. Consumption data in Germany for different age groups are provided by the
National Nutrition Survey ll, VELS, EsKiMo and the ongoing KiESEL study. The data
for the levels of substances in foods is currently obtained from the German food
monitoring programme (Lebensmittel-Monitoring) and the German Food Composition
Table (Bundeslebensmittelschlussel) and is not sufficient for a comprehensive
evaluation of dietary exposure in Germany. More data is needed and, in
particular, the range of analysed substances should be broadened to reduce the
uncertainties of the exposure assessment. A representative data basis for
concentrations of substances in foods will be established with the first German
total diet study, called the BfR MEAL study. The study will markedly reduce major
uncertainties in the dietary exposure assessment through its wide coverage of
substances in food groups, the inclusion of prepared foods, the orientation on
low measurement limits as well as the analysis of substances without a reliable
data basis.
PMID- 28516261
TI - [Metals and their compounds as contaminants in food : Arsenic, cadmium, lead and
aluminum].
AB - Metals and their compounds are ubiquitously distributed in the environment, thus
reaching plant and animal derived food. While actual exposure levels in Europe do
not give rise to concern for acute toxicity, chronic toxicity of some metals and
metalloids cannot be completely ruled out. Thus, in the case of inorganic
arsenic, an elevated risk of carcinogenicity in different organs cannot be
excluded even under actual dietary exposure conditions. In the case of cadmium,
nephrotoxicity may be a particular problem for certain subgroups, such as
children. Regarding lead, exposure levels have dropped considerably during the
last two decades; nevertheless, developmental neurotoxicity may still be a
problem during prenatal development and early childhood. Also in the case of
aluminum current dietary exposure levels are close to the tolerable weekly intake
(TWI) value derived by the European Food Safety Authority (EFSA). Taken together,
for all four examples, further reductions in exposure levels are required.
PMID- 28516262
TI - [Nanomaterials in foodstuffs - toxicological properties and risk assessment].
AB - Nanomaterials measure below 100 nm in size in at least one dimension. In general,
organic and inorganic nanoparticles can be distinguished. In addition, nanosized
structures may differ substantially with regard to their shape, chemical
composition and physical properties. They may originate either from natural
processes or can be manufactured intentionally. The possible specific
toxicological properties of nanoparticles that might be based on their enhanced
reactivity due to an increased surface-to-volume ratio, as compared to larger
particles, or which might result from preferential uptake in cells and tissues,
are the subject of current toxicological research. Consumers are exposed to
nanomaterials via the oral route by foodstuffs containing naturally formed,
unknowingly incorporated or intentionally added nanoparticles. In the course of
this work, an overview of the occurrence of nanomaterials in foodstuffs,
including the legal definition and labeling requirements, will be given.
Furthermore, specific characteristics of the oral uptake of nanomaterials will be
presented alongside challenges for experimental investigation of gastrointestinal
uptake and the effects of nanoscaled particles. These will be discussed in
relation to potentially relevant toxicological properties and modes of action.
Despite a plethora of available experimental studies, there are still knowledge
gaps with regard to the exposure against orally ingested nanoparticles and with
regard to possible toxicological consequences of such particles in order to allow
for accurate risk assessment of the materials in foodstuffs and food packaging.
PMID- 28516263
TI - [Social inequalities in the prevalence of chronic back pain among adults in
Germany].
AB - BACKGROUND: Back pain is a common cause for health care utilization and inability
to work and associated with corresponding costs. The aim of the study was to
investigate socioeconomic inequalities in chronic back pain in the adult general
population. METHODS: The analyses were based on pooled data of three waves (2009,
2010, 2012) of the nationwide German Health Update (GEDA) study carried out by
the Robert Koch Institute (n = 62,606 aged 18 years and older). Self-reported
back pain symptoms persisting at least three months were used to determine
lifetime and 12-month prevalence. For analyzing socioeconomic differences in the
prevalence of chronic back pain, a multidimensional SES index and its three
individual components - educational level, occupational status and income - were
used. RESULTS: About every sixth man (17.1%) and every fourth woman (24.4%)
reported chronic back pain in the past twelve months. With decreasing SES, the 12
month prevalence of chronic back pain increased (Relative Index of Inequality
(RII) [95% CI], men = 2.29 [2.04-2,56], women=1.92 [1.76-2.09]). Similar results
were observed for lifetime prevalence. For both men and women, educational level,
occupational status and income each had independent effects on chronic back pain
prevalence. CONCLUSION: In Germany, back pain is widely prevalent. Our finding
that different aspects of SES are independently associated with chronic back pain
prevalence is a challenge but also a chance for treatment and preventive
strategies combining behavioral and setting-oriented measures.
PMID- 28516264
TI - A Response to Commentaries on "Beyond Sexual Orientation: Integrating Gender/Sex
and Diverse Partnered Sexualities via Sexual Configurations Theory" (van Anders,
2015).
PMID- 28516265
TI - The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and
prevention.
AB - Vitamin D deficiency and insufficiency is a global health issue that afflicts
more than one billion children and adults worldwide. The consequences of vitamin
D deficiency cannot be under estimated. There has been an association of vitamin
D deficiency with a myriad of acute and chronic illnesses including preeclampsia,
childhood dental caries, periodontitis, autoimmune disorders, infectious
diseases, cardiovascular disease, deadly cancers, type 2 diabetes and
neurological disorders. This review is to put into perspective the controversy
surrounding the definition for vitamin D deficiency and insufficiency as well as
providing guidance for how to treat and prevent vitamin D deficiency.
PMID- 28516268
TI - GPNA inhibits the sodium-independent transport system L for neutral amino acids.
AB - L-gamma-Glutamyl-p-nitroanilide (GPNA) is widely used to inhibit the glutamine
transporter ASCT2, although it is known that it also inhibits other sodium
dependent amino acid transporters. In a panel of human cancer cell lines, which
express the system L transporters LAT1 and LAT2, GPNA inhibits the sodium
independent influx of leucine and glutamine. The kinetics of the effect suggests
that GPNA is a low affinity, competitive inhibitor of system L transporters. In
Hs683 human oligodendroglioma cells, the incubation in the presence of GPNA, but
not ASCT2 silencing, lowers the cell content of leucine. Under the same
conditions the activity of mTORC1 is inhibited. Decreased cell content of
branched chain amino acids and mTORC1 inhibition are observed in most of the
other cell lines upon incubation with GPNA. It is concluded that GPNA hinders the
uptake of essential amino acids through system L transporters and lowers their
cell content.
PMID- 28516269
TI - beta-Alanine intercede metabolic recovery for amelioration of human cervical and
renal tumors.
AB - beta-Alanine is a non-essential amino acid and presents as a major component of
various sports supplements. It is a non-proteogenic amino acid, formed in vivo by
degradation of carnosine, anserine, balenine, and dihydrouracil. The present
study was aimed at investigating the anti-tumor effects of beta-alanine in renal
and cervical tumor cells. Sulforhodamine-B assay and flow cytometric analysis
were used to measure cell viability. Lactate dehydrogenase (LDH) expression was
analyzed using FITC-conjugated fluorescent antibody. The cellular adenosine
triphosphate (ATP) content was measured using bioluminescence method. Cell
migration was determined by the simple standard-scratch method. beta-Alanine
reduced renal and cervical cell growth significantly. Percentage of inhibition of
renal and cervical tumor cells was increased at higher concentration of beta
alanine. LDH expression and ATP content were significantly reduced in renal and
cervical tumor cells in a dose-dependent manner. Renal and cervical tumor cell
migration were significantly reduced following 10 and 100 mM of beta-alanine
treatment. In our study, beta-alanine exerts no significant effect on normal MDCK
cells except a marginal effect at the highest concentration (100 mM). In summary,
our experimental data suggest that beta-alanine may be a potential anti-tumor
agent exhibiting several anti-cancer effects in renal and cervical tumor cells.
PMID- 28516266
TI - Constitutive calcium entry and cancer: updated views and insights.
AB - Tight control of basal cytosolic Ca2+ concentration is essential for cell
survival and to fine-tune Ca2+-dependent cell functions. A way to control this
basal cytosolic Ca2+ concentration is to regulate membrane Ca2+ channels
including store-operated Ca2+ channels and secondary messenger-operated channels
linked to G-protein-coupled or tyrosine kinase receptor activation. Orai, with or
without its reticular STIM partner and Transient Receptor Potential (TRP)
proteins, were considered to be the main Ca2+ channels involved. It is well
accepted that, in response to cell stimulation, opening of these Ca2+ channels
contributes to Ca2+ entry and the transient increase in cytosolic Ca2+
concentration involved in intracellular signaling. However, in various
experimental conditions, Ca2+ entry and/or Ca2+ currents can be recorded at rest,
without application of any experimental stimulation. This led to the proposition
that some plasma membrane Ca2+ channels are already open/activated in basal
condition, contributing therefore to constitutive Ca2+ entry. This article
focuses on direct and indirect observations supporting constitutive activity of
channels belonging to the Orai and TRP families and on the mechanisms underlying
their basal/constitutive activities.
PMID- 28516267
TI - Methods of Candida dubliniensis identification and its occurrence in human
clinical material.
AB - Candida dubliniensis was reported as a new species in 1995. This species is often
misidentified as Candida albicans. The aims of this work were to determine the
occurrence of C. dubliniensis in various clinical materials, to evaluate several
ways to identify it and to examine the genetic variability of isolates. Among
7706 isolates originally identified as C. albicans, 237 were identified as C.
dubliniensis (3.1%). Most of the C. dubliniensis isolates were obtained from the
upper and lower respiratory tract (61.4 and 22.9%). Five phenotypic methods
including latex agglutination were used (cultivation on CHROMagar Candida, on
Staib agar, at 42 degrees C and in medium with 6.5% NaCl), but only cultivation
on the medium with an increased concentration of NaCl and latex agglutination
gave reliable results. Species-specific polymerase chain reaction was used as the
confirmation method. Matrix-assisted laser desorption ionization time-of-flight
mass spectrometry provided less reliable results. In fact, 78.9% of C.
dubliniensis isolates had scores above 1.7. However, the rest of them (21.1%)
were also identified as C. dubliniensis even when the scores were lower than 1.7.
Divergences among C. dubliniensis strains were evaluated by means of pulsed-field
gel electrophoresis. Eighty-six selected C. dubliniensis isolates showed a 69.6%
level of similarity. The results of this study expand the knowledge of the
incidence, means of identification and genotypic divergence of C. dubliniensis
isolates.
PMID- 28516270
TI - [Ocular sarcoidosis].
AB - Ocular manifestation of sarcoidosis occurs in up to 60% of patients with
confirmed systemic sarcoidosis and represents one of the most common forms of
noninfectious uveitis. In known pulmonary sarcoidosis, ocular involvement can
occur in up to 80% of cases. Sarcoidosis can also present only in the eye,
without a systemic manifestation (ocular sarcoidosis). Typically, ocular
sarcoidosis shows bilateral granulomatous uveitis and can involve all parts of
the eye. Apart from an acute anterior uveitis, chronic intermediate or posterior
uveitis can be found. In order to prevent a severe reduction of visual acuity
leading to blindness, early diagnosis and treatment is essential. For diagnosis,
specific clinical signs involving the eye (bilateral granulomatous changes in all
parts of the eye) and typical laboratory investigations (angiotensin-converting
enzyme, ACE; lysozyme; soluble interleukin 2 receptor, sIL2R; chest X-ray; chest
CT) have to be taken into account, since biopsy to prove noncaseating granulomas
is not performed with changes restricted to the eye due to the high risk of
vision loss. Ocular sarcoidosis mostly responds well to local or systemic steroid
treatment. If the therapeutic effect is insufficient, immunosuppressive agents
and biologics can be applied.
PMID- 28516272
TI - Uterine Artery Embolization for Symptomatic Adenomyosis: 7-Year Clinical Follow
up Using UFS-Qol Questionnaire.
AB - PURPOSE: The purpose of this study was to assess clinical outcomes 7 years after
uterine artery embolization (UAE) in the treatment of symptomatic adenomyosis.
MATERIALS AND METHODS: In this prospective cohort study, one specialized hospital
in the Netherlands recruited patients with symptomatic adenomyosis or adenomyosis
in combination with fibroids for UAE. The 7-year post-intervention outcomes were
health-related quality of life (HRQOL), symptom severity scores (SSS),
satisfaction, menopause and re-interventions. RESULTS: Twenty-nine patients with
adenomyosis (15 with fibroids) were treated with UAE between September 2006 and
January 2010. The 7-year questionnaire was mailed in November 2016. The mean
follow-up was 95 months (SD 9.0) at a mean age of 50 (SD 5.4). Questionnaires
were returned by 24/29 patients (83%). The remaining five patients were contacted
through telephone. One of these patients was untraceable. Seven years after
treatment 5 of 28 patients (18%) underwent a secondary hysterectomy. The HRQOL
and SSS scores as measured by UFS-QOL at 3 months after UAE showed significant
improvement of -57 points (score: 15) and +40 points (score: 91), respectively.
These scores remained comparable stable up unto 7 years. The SSS showed a
significant difference of 17 points (0-100) in favor of the adenomyosis in
combination with fibroids group (p = 0.020). Menopause was reported by 10/28
patients (36%). Twenty-one of 29 (72%) patients declared to be at least fairly
satisfied about UAE. CONCLUSIONS: After 7 years of follow-up, in 82% of UAE
treated patients with symptomatic adenomyosis a hysterectomy was avoided.
PMID- 28516271
TI - Three-dimensional Image Fusion Guidance for Transjugular Intrahepatic
Portosystemic Shunt Placement.
AB - INTRODUCTION: To assess the safety, feasibility and effectiveness of image fusion
guidance with pre-procedural portal phase computed tomography with
intraprocedural fluoroscopy for transjugular intrahepatic portosystemic shunt
(TIPS) placement. MATERIALS AND METHODS: All consecutive cirrhotic patients
presenting at our interventional unit for TIPS creation from January 2015 to
January 2016 were prospectively enrolled. Procedures were performed under general
anesthesia in an interventional suite equipped with flat panel detector, cone
beam computed tomography (CBCT) and image fusion technique. All TIPSs were placed
under image fusion guidance. After hepatic vein catheterization, an unenhanced
CBCT acquisition was performed and co-registered with the pre-procedural portal
phase CT images. A virtual path between hepatic vein and portal branch was made
using the virtual needle path trajectory software. Subsequently, the 3D virtual
path was overlaid on 2D fluoroscopy for guidance during portal branch
cannulation. Safety, feasibility, effectiveness and per-procedural data were
evaluated. RESULTS: Sixteen patients (12 males; median age 56 years) were
included. Procedures were technically feasible in 15 of the 16 patients (94%).
One procedure was aborted due to hepatic vein catheterization failure related to
severe liver distortion. No periprocedural complications occurred within 48 h of
the procedure. The median dose-area product was 91 Gy cm2, fluoroscopy time 15
min, procedure time 40 min and contrast media consumption 65 mL. Clinical benefit
of the TIPS placement was observed in nine patients (56%). CONCLUSION: This study
suggests that 3D image fusion guidance for TIPS is feasible, safe and effective.
By identifying virtual needle path, CBCT enables real-time multiplanar guidance
and may facilitate TIPS placement.
PMID- 28516274
TI - Evaluation of a New Esophageal Stent for the Treatment of Malignant and Benign
Esophageal Strictures.
AB - PURPOSE: To evaluate the efficacy and safety of the EGIS esophageal stent for
treating malignant and benign esophageal strictures. MATERIALS AND METHODS: Data
of 73 patients (mean age 63.0 +/- 11.9 years; 66 males) with malignant esophageal
stricture and 16 patients (mean age 63.7 +/- 9.5 years; 13 males) with benign
esophageal stricture who received the EGIS esophageal stent (S&G Biotech,
Seongnam, Korea) between October 2010 and April 2016 were obtained from a
prospectively maintained electronic database. RESULTS: Technical and clinical
success rates were 100% (89/89). Stent malfunction (i.e., tumor/tissue
overgrowth, stent migration, and food impaction) occurred in 20.5% (15/73) and
37.5% (6/16) of patients with malignant and benign esophageal strictures,
respectively. Stent migration occurred in five (6.8%) and four (25%) patients
with malignant and benign esophageal strictures, respectively. The median follow
up durations in patients with malignant and benign esophageal strictures were 130
[interquartile range (IQR) 76-322] days and 486 (IQR 315-736) days, respectively.
Recurrent dysphagia occurred in 14.1% (10/73) and 87.5% (14/16) of patients with
malignant and benign esophageal strictures, respectively. The median recurrence
free durations in patients with malignant and benign esophageal strictures were
126 (IQR 69-259) days and 100 (IQR 40-182) days, respectively. CONCLUSION: The
EGIS esophageal stent appears to be effective for malignant esophageal
strictures, with relatively low rate of stent migration, whereas, for benign
esophageal strictures, it seems to be associated with a high rate of recurrent
dysphagia, mainly due to stent migration.
PMID- 28516273
TI - A Comparative Study of Ablation Boundary Sharpness After Percutaneous
Radiofrequency, Cryo-, Microwave, and Irreversible Electroporation Ablation in
Normal Swine Liver and Kidneys.
AB - PURPOSE: To compare ablation boundary sharpness after percutaneous radiofrequency
ablation (RFA), cryoablation (CA), microwave ablation (MWA) and irreversible
electroporation (IRE) ablation in normal swine liver and kidney. MATERIALS AND
METHODS: Percutaneous CT-guided RFA (n = 5), CA (n = 5), MWA (n = 5) and IRE (n =
5) were performed in the liver and kidney of four Yorkshire pigs. Parameters were
chosen to produce ablations 2-3 cm in diameter with a single ablation probe.
Contrast-enhanced CT imaging was performed 24 h after ablation, and animals were
killed. Treated organs were removed and processed for histologic analysis with
hematoxylin and eosin, and terminal deoxynucleotidyl transferase dUTP nick end
labeling (TUNEL). Three readers independently analyzed CT, H&E and TUNEL stained
images of the ablation boundary to delineate regions of (1) viable cells, (2)
complete necrosis or (3) mixture of viable and necrotic cells which was defined
as the transition zone (TZ). The width of TZ was compared across the techniques
and organs. RESULTS: Ablations appeared as non-contrast-enhancing regions on CT
with sharp transition to enhancing normal tissue. On TUNEL stained slides, the
mean width (MUm) of the TZ after MWA was 319 +/- 157 in liver and 267 +/- 95 in
kidney, which was significantly lower than RFA (811 +/- 477 and 938 +/- 429); CA
(452 +/- 222 and 700 +/- 563); and IRE (1319 +/- 682 and 1570 +/- 962) (all p <
0.01). No significant differences were observed between the organs. CONCLUSION:
Under similar conditions, the width of the TZ at the ablation boundary varies
significantly between different ablation techniques.
PMID- 28516275
TI - The Role of Cardiac Biomarkers in Pregnancy.
AB - OPINION STATEMENT: Cardiovascular disease (CVD) is the leading cause of pregnancy
associated mortality, with an increasingly complex pregnant population. While our
understanding of CVD in pregnancy continues to evolve, there remains a need to
develop widely accessible tools to follow pregnant women both with and without
preexisting disease with respect to cardiovascular risk, particularly for those
presenting with symptoms suggestive of cardiovascular pathology. Thus, research
is emerging with respect to the potential role of novel and established cardiac
biomarkers in diagnosing and following CVD in pregnancy. Here, we review the
normal hemodynamics of pregnancy and the behavior of various biomarkers in both
normal and complicated pregnancies.
PMID- 28516277
TI - Analysis of cellular autofluorescence in touch samples by flow cytometry:
implications for front end separation of trace mixture evidence.
AB - The goal of this study was to survey optical and biochemical variation in cell
populations deposited onto a surface through touch or contact and identify
specific features that may be used to distinguish and then sort cell populations
from separate contributors in a trace biological mixture. Although we were not
able to detect meaningful biochemical variation in touch samples deposited by
different contributors through preliminary antibody surveys, we did observe
distinct differences in red autofluorescence emissions (650-670 nm), with as much
as a tenfold difference in mean fluorescence intensities observed between certain
pairs of donors. Results indicate that the level of red autofluorescence in touch
samples can be influenced by a donor's contact with specific material prior to
handling the substrate from which cells were collected. In particular, we
observed increased red autofluorescence in cells deposited subsequent to handling
laboratory gloves, plant material, and certain types of marker ink, which could
be easily visualized microscopically or using flow cytometry, and persisted after
hand washing. To test whether these observed optical differences could
potentially be used as the basis for a cell separation workflow, a controlled two
person touch mixture was separated into two fractions via fluorescence-activated
cell sorting (FACS) using gating criteria based on intensity of 650-670 nm
emissions and then subjected to DNA analysis. Genetic analysis of the sorted
fractions provided partial DNA profiles that were consistent with separation of
individual contributors from the mixture suggesting that variation in
autofluorescence signatures, even if driven by extrinsic factors, may nonetheless
be a useful means of isolating contributors to some touch mixtures. Graphical
Abstract Conceptual workflow diagram. Trace biological mixtures containing cells
from multiple individuals are analyzed by flow cytometry. Cells are then
physically separated into two populations based on intensity of red
autofluorescence using Fluorescence Activated Cell Sorting. Each isolated cell
fraction is subjected to DNA analysis resulting in a DNA profile for each
contributor.
PMID- 28516276
TI - P2X7 receptor-pannexin 1 interaction mediates extracellular alpha-synuclein
induced ATP release in neuroblastoma SH-SY5Y cells.
AB - Abnormalities of alpha-synuclein (ASN), the main component of protein deposits
(Lewy bodies), were observed in Parkinson's disease (PD), dementia with Lewy
bodies, Alzheimer's disease, and other neurodegenerative disorders. These
alterations include increase in the levels of soluble ASN oligomers in the
extracellular space. Numerous works have identified several mechanisms of their
toxicity, including stimulation of the microglial P2X7 receptor leading to
oxidative stress. While the significant role of purinergic signaling
particularly, P2 family receptors-in neurodegenerative disorders is well known,
the interaction of extracellular soluble ASN with neuronal purinergic receptors
is yet to be studied. Therefore, in this study, we have investigated the effect
of ASN on P2 purinergic receptors and ATP-dependent signaling. We used
neuroblastoma SH-SY5Y cell line and rat synaptoneurosomes treated with exogenous
soluble ASN. The experiments were performed using spectrofluorometric,
radiochemical, and immunochemical methods. We found the following: (i) ASN
induced intracellular free calcium mobilization in neuronal cells and nerve
endings depends on the activation of purinergic P2X7 receptors; (ii) activation
of P2X7 receptors leads to pannexin 1 recruitment to form an active complex
responsible for ATP release; and (iii) ASN greatly decreases the activity of
extracellular ecto-ATPase responsible for ATP degradation. Thus, it is concluded
that purinergic receptors might be putative pharmacological targets in the
molecular mechanism of extracellular ASN toxicity. Interference with P2X7
signaling seems to be a promising strategy for the prevention or therapy of PD
and other neurodegenerative disorders.
PMID- 28516280
TI - Optimization of an ultrasound-assisted derivatization for GC/MS analysis of
oxygenated organic species in atmospheric aerosol.
AB - A novel ultrasound-assisted derivatization followed by GC/MS analysis was
developed for the quantification of oxygenated organic species in ambient
aerosol. Derivatization parameters mostly influencing the analytical response
were investigated, i.e., solvent type, reagent concentration, and reaction
duration. Response surface methodology was used to design experiments and a
quadratic model was utilized to predict the variables and establish the optimal
conditions. The study was performed on standard solutions of 30 compounds
representing the major classes of oxygenated compounds typically found in ambient
aerosol, i.e., low molecular weight carboxylic acids, sugars, and phenols. In
comparison with conventional methods, the optimized procedure uses mild reaction
temperature (room temperature instead of 70 degrees C), reduces the amount of
silyl reagent (24 vs. 40 MUL), and shortens derivatization times (45 vs. 70 min),
participating in the current trend of analytical chemistry towards clean, green
methods that reduce costs and decrease pollution. Once optimized, the ultrasound
procedure was validated by assessing for repeatability, linearity, detection
limits, and derivative stability. For all oxygenated organic species, the
proposed method showed a good reproducibility-as the relative standard deviations
(RSDs%, n = 5) of intra-day analysis were <=7% - a good linearity with the
correlation coefficients of calibration curves R 2 >= 99.8, and low detection
limits, ranging from 0.34 to 6.50 ng MUL-1; thus it is suitable for its
applicability in air quality monitoring. Finally, this method was successfully
applied to determine 30 oxygenated organic species in three ambient PM2.5 samples
collected at an urban site in Northern Italy in three different seasons.
Graphical abstract Ultrasound-assisted derivatization is a green alternative
method for GC/MS analysis of oxygenated organic species in atmospheric aerosol
towards reduction of energy and reactive consumption.
PMID- 28516279
TI - A new carbon-based magnetic material for the dispersive solid-phase extraction of
UV filters from water samples before liquid chromatography-tandem mass
spectrometry analysis.
AB - Magnetic solid-phase extraction is one of the most promising new extraction
methods for liquid samples before ultra-high-performance liquid chromatography
tandem mass spectrometry (UHPLC-MS/MS) analysis. Several types of materials,
including carbonaceous ones, have been prepared for this purpose. In this paper,
for the first time, the preparation, characterization, and sorption capability of
Fe3O4-graphitized carbon black (mGCB) composite toward some compounds of
environmental interest were investigated. The synthesized mGCB consisted of
micrometric GCB particles with 55 m2 g-1 surface area bearing some carbonyl and
hydroxyl functionalities and the surface partially decorated by Fe3O4
microparticles. The prepared mGCB was firstly tested as an adsorbent for the
extraction from surface water of 50 pollutants, including estrogens,
perfluoroalkyl compounds, UV filters, and quinolones. The material showed good
affinity to many of the tested compounds, except carboxylates and glucoronates;
however, some compounds were difficult to desorb. Ten UV filters belonging to the
chemical classes of benzophenones and p-aminobenzoates were selected, and
parameters were optimized for the extraction of these compounds from surface
water before UHPLC-MS/MS determination. Then, the method was validated in terms
of linearity, trueness, intra-laboratory precision, and detection and
quantification limits. In summary, the method performance (trueness, expressed as
analytical recovery, 85-114%; RSD 5-15%) appears suitable for the determination
of the selected compounds at the level of 10-100 ng L-1, with detection limits in
the range of 1-5 ng L-1. Finally, the new method was compared with a published
one, based on conventional solid-phase extraction with GCB, showing similar
performance in real sample analysis. Graphical Abstract Workflow of the
analytical method based on magnetic solid-phase extraction followed by LC-MS/MS
determination.
PMID- 28516278
TI - Molecularly imprinted polymers based stir bar sorptive extraction for
determination of cefaclor and cefalexin in environmental water.
AB - Although stir bar sportive extraction was thought to be a highly efficiency and
simple pretreatment approach, its wide application was limited by low
selectivity, short service life, and relatively high cost. In order to improve
the performance of the stir bar, molecular imprinted polymers and magnetic carbon
nanotubes were combined in the present study. In addition, two monomers were
utilized to intensify the selectivity of molecularly imprinted polymers. Fourier
transform infrared spectroscopy, scanning electron microscopy, and selectivity
experiments showed that the molecularly imprinted polymeric stir bar was
successfully prepared. Then micro-extraction based on the obtained stir bar was
coupled with HPLC for determination of trace cefaclor and cefalexin in
environmental water. This approach had the advantages of stir bar sportive
extraction, high selectivity of molecular imprinted polymers, and high sorption
efficiency of carbon nanotubes. To utilize this pretreatment approach, pH,
extraction time, stirring speed, elution solvent, and elution time were
optimized. The LOD and LOQ of cefaclor were found to be 3.5 ng . mL-1 and 12.0 ng
. mL-1, respectively; the LOD and LOQ of cefalexin were found to be 3.0 ng . mL-1
and 10.0 ng . mL-1, respectively. The recoveries of cefaclor and cefalexin were
86.5 ~ 98.6%. The within-run precision and between-run precision were acceptable
(relative standard deviation <7%). Even when utilized in more than 14 cycles, the
performance of the stir bar did not decrease dramatically. This demonstrated that
the molecularly imprinted polymeric stir bar based micro-extraction was a
convenient, efficient, low-cost, and a specific method for enrichment of cefaclor
and cefalexin in environmental samples.
PMID- 28516281
TI - ToF-SIMS study of differentiation of human bone-derived stromal cells: new
insights into osteoporosis.
AB - Lipids have numerous important functions in the human body, as they form the
cells' plasma membranes and play a key role in many disease states, presumably
also in osteoporosis. Here, the fatty acid composition of the outer plasma
membranes of cells differentiated into the osteogenic and adipogenic direction is
studied with surface-sensitive time-of-flight secondary ion mass spectrometry
(ToF-SIMS). For data evaluation, principal component analysis (PCA) is applied.
Human (bone-derived) mesenchymal stromal cells (hMSCs) from an osteoporotic donor
and a control donor are compared to reveal differences in the fatty acid
composition of the membranes. The chemical information is correlated to staining
and real-time quantitative polymerase chain reaction (rt-qPCR) results to provide
insight into the gene expression of several differentiation markers on the RNA
level. Adipogenic differentiation of hMSCs from a non-osteoporotic donor
correlates with increased relative intensities of all fatty acids under
investigation. After osteogenic differentiation of non-osteoporotic cells, the
relative mass signal intensities of unsaturated fatty acids such as oleic and
linoleic acids are increased. However, the osteoporotic cells show increased
levels of palmitic acid in the plasma membrane after exposure to osteogenic
differentiation conditions, which correlates to an immature differentiation state
relative to non-osteoporotic osteogenic cells. This immature differentiation
state is confirmed by increased early osteogenic differentiation factor Runx2 on
RNA level and by less calcium mineralization spots seen in von Kossa staining and
ToF-SIMS images. Graphical abstract Time-of-flight secondary ion mass
spectrometry is applied to analyze the fatty acid composition of the outer plasma
membranes of cells differentiated into the adipogenic and osteogenic direction.
Cells from an osteoporotic and a control donor are compared to reveal differences
due to differentiation and disease stage of the cells.
PMID- 28516282
TI - Region-Specific Iron Measured by MRI as a Biomarker for Parkinson's Disease.
AB - The identification of sensitive and specific biomarkers for Parkinson's disease
(PD) poses an important clinical challenge. A potential biomarker for early
diagnosis and disease monitoring of PD is region-specific iron. Iron accumulation
in the substantia nigra pars compacta is considered a main characteristic of PD.
However, questions remain, such as the relationship between nigral iron and
clinical indices of PD (motor impairment or disease duration). Further, previous
studies have suggested the influence of iron on other nuclei. Iron quantification
using magnetic resonance imaging (MRI) allows for studies of the relationship
between regional iron and clinical symptoms in vivo. Thus, in this review we
discuss the following topics: the technological development of MRI in measuring
brain iron, nigral iron as a potential marker for PD in both clinical and
prodromal stages, other influences of regional iron on PD, and clinical
translation and future perspectives.
PMID- 28516283
TI - Developmental window of sensorineural deafness in biotinidase-deficient mice.
AB - Biotinidase deficiency is an autosomal recessively inherited disorder that
results in the inability to recycle the vitamin, biotin. If untreated, the
disorder can result in a range of neurological and cutaneous symptoms, including
sensorineural deficits and deafness. To understand early mechanistic
abnormalities that may precede more generalized and nonspecific effects of
metabolic deficits such as weight loss and acidosis, we have analyzed auditory
brainstem responses (ABRs) in biotinidase-deficient knockout (Btd -/- ) mice in
the periweaning period with or without dietary biotin supplementation. We find
significant increases in the latency of wave V of the ABR elicited by pure tone
stimuli at one octave intervals, which precede substantial increases in ABR
thresholds. Finer interpeak latency analyses of these changes indicate they are
confined to the latter ABR waves associated with the CNS and likely reflect
slowed brainstem transmission time. In contrast, peripheral nervous system
conduction velocity appears normal. Further, we find that biotin-supplementation
after the onset of symptoms reverses the latency shifts, which has significant
relevance for early treatment in patients. Finally, ABR latencies in Btd -/- mice
fed a biotin-supplemented diet for the first month of life appear refractory to
transmission time slowing during a subsequent bout of biotin deficiency. These
data suggest a transient vulnerability window for biotin deficiency in the
auditory brainstem. Finally, we also observe a developmental vulnerability window
involving follicular melanosome production or melanocyte survival. Sensorineural
deafness precedes peripheral hearing loss in developmental biotinidase deficiency
and is transient if rescued by dietary biotin within a short developmental
window.
PMID- 28516285
TI - Intracellular morphological changes in Staphylococcus aureus induced by treatment
with sodium hypochlorite.
AB - Sodium hypochlorite (NaOCl) is commonly used as a disinfectant; however, its
bactericidal mechanism has not yet been clarified. In the present study, the
bactericidal mechanism of NaOCl was examined using microscopy and gel
electrophoresis techniques with Staphylococcus aureus strain 209P. S. aureus
cells treated with 500 and 1000 ppm NaOCl for 5 and 15 min were observed by SEM
and TEM. SEM images of the bacterial cells treated with NaOCl showed an irregular
surface, with cells being partially invaginated. TEM images of the bacterial
cells showed cytoplasmic alterations, accompanied by a partially irregular
cellular surface. Under a fluorescence microscope, we clearly observed
fluorescence quenching in the 1000 ppm NaOCl-treated cells. Based on these
observations, which indicated that NaOCl damaged chromosomal DNA, we next
extracted chromosomal DNA from bacterial cells treated with NaOCl and performed
agarose gel electrophoresis. Chromosomal DNA was absent in the DNA sample from
the bacterial cells treated with 500 ppm NaOCl. From these biochemical results,
it was strongly suggested that NaOCl degrades the chromosomal DNA of S. aureus.
We consider that the morphological changes in the cytoplasm induced by NaOCl may
be related to NaOCl-induced degradation of S. aureus chromosomal DNA.
PMID- 28516284
TI - Short-chain acyl-CoA dehydrogenase deficiency: from gene to cell pathology and
possible disease mechanisms.
AB - Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is an inherited disorder of
mitochondrial fatty acid oxidation that is characterized by the presence of
increased butyrylcarnitine and ethylmalonic acid (EMA) concentrations in plasma
and urine. Individuals with symptomatic SCADD may show relatively severe
phenotype, while the majority of those who are diagnosed through newborn
screening by tandem mass spectrometry may remain asymptomatic. As such, the
associated clinical symptoms are very diverse, ranging from severe metabolic or
neuromuscular disabilities to asymptomatic. Molecular analysis of affected
individuals has identified rare gene variants along with two common gene
variants, c.511C > T and c.625G > A. In vitro studies have demonstrated that the
common variants as well as the great majority of rare variants, which are
missense variants, impair folding, that may lead to toxic accumulation of the
encoded protein, and/or metabolites, and initiate excessive production of ROS and
chronic oxidative stress. It has been suggested that this cell toxicity in
combination with yet unknown factors can trigger disease development. This
association and the full implications of SCADD are not commonly appreciated.
Accordingly, there is a worldwide discussion of the relationship of clinical
manifestation to SCADD, and whether SCAD gene variants are disease associated at
all. Therefore, SCADD is not part of the newborn screening programs in most
countries, and consequently many patients with SCAD gene variants do not get a
diagnosis and the possibilities to be followed up during development.
PMID- 28516287
TI - Spread of poxviruses in livestock in Brazil associated with cases of double and
triple infection.
AB - The objective of this work is to describe the distribution of outbreaks of
vaccinia virus (VACV), pseudocowpox virus (PCPV), and bovine papular stomatitis
virus (BSPV) in Brazil. The Official Laboratory of the Brazilian Ministry of
Agriculture received 89 samples from different locations in Brazil in 2015 and
2016 for diagnosis of vesicular and exanthematous disease. Poxvirus coinfections
occurred in 11 out of 33 outbreaks, including the first reported triple infection
by BPSV, PCPV, and VACV. This occurrence may be associated with the circulation
of these viruses in Brazilian cattle.
PMID- 28516286
TI - Establishment of a tumor sphere cell line from a metastatic brain neuroendocrine
tumor.
AB - Neuroendocrine tumors are rare, and little is known about the existence of cancer
stem cells in this disease. Identification of the tumorigenic population will
contribute to the development of effective therapies targeting neuroendocrine
tumors. Surgically resected brain metastases from a primary neuroendocrine tumor
of unknown origin were dissociated and cultured in serum-free neurosphere medium.
Stem cell properties, including self-renewal, differentiation potential, and stem
cell marker expression, were examined. Tumor formation was evaluated using
intracranial xenograft models. The effect of temozolomide was measured in vitro
by cell viability assays. We established the neuroendocrine tumor sphere cell
line ANI-27S, which displayed stable exponential growth, virtually unlimited
expansion in vitro, and expression of stem-cell markers such as CD133, nestin,
Sox2, and aldehyde dehydrogenase. FBS-induced differentiation decreased Sox2 and
nestin expression. On the basis of real-time PCR, ANI-27S cells expressed the
neuroendocrine markers synaptophysin and chromogranin A. Intracranial
xenotransplanted brain tumors recapitulated the original patient tumor and
temozolomide exhibited cytotoxic effects on tumor sphere cells. For the first
time, we demonstrated the presence of a sphere-forming, stem cell-like population
in brain metastases from a primary neuroendocrine tumor. We also demonstrated the
potential therapeutic effects of temozolomide for this disease.
PMID- 28516288
TI - Efficacy and Safety of Ibuprofen in Infants Aged Between 3 and 6 Months.
AB - Ibuprofen is a non-steroidal anti-inflammatory drug frequently administered to
children of various ages for relief of fever and pain and is approved as an over
the-counter medication in many countries worldwide. Although there are extensive
data on its efficacy and safety in children and adults, there are divergent
dosing recommendations for analgesia and treatment of fever in infants,
especially in the age group between 3 and 6 months of age. In this article, we
have assessed the safety and efficacy of ibuprofen use in infants in an attempt
to find the optimal method of pain and fever management in this specific age
group. Based on the current evidence, short-term use of ibuprofen is considered
safe in infants older than 3 months of age having a body weight above 5-6 kg when
special attention is given to the hydration of the patient. Ibuprofen should be
prescribed based on body weight using a dose of 5-10 mg/kg. This dose can be
administered 3-4 times a day resulting in a maximum total daily dose of 30-40
mg/kg. The rectal route has been shown to be less reliable because of erratic
absorption, especially in young infants. Since most efficacy and safety data have
been derived from trials in infants with fever, future studies should focus on
the efficacy of ibuprofen in young infants with pain.
PMID- 28516289
TI - Understanding the Stability of Dopamine and Dobutamine Over 24 h in Simulated
Neonatal Ward Conditions.
AB - OBJECTIVES: Our objectives were to investigate the possible effects of
temperature and light on the stability of dopamine and dobutamine continuous
infusions over 24 h when prepared in a variety of dilution vehicles. METHODS:
Syringe-driver infusion apparatuses were set up for dopamine and dobutamine
diluted with either 0.9% sodium chloride (NaCl) or 5% glucose delivering 3 and 5
MUg/kg/min, respectively, via 206-cm extension sets. All infusions were prepared
for a neonate weight of 1 kg. Infusions were run over 24 h with approximately
half the tubing within an incubator set at 35 degrees C. Cyclic voltammetry was
used to monitor the concentration of the inotrope within the syringe and at the
end of the extension set, both initially and after 24 h. RESULTS: The variation
in the concentration of dopamine and dobutamine in the vials (n = 6) was 3.58 and
1.22%, respectively. This variation increased to 10.88% for dopamine and 5.76%
for dobutamine in the syringe. After 24 h, a significant reduction in the
concentration of dopamine was observed at the end of the extension set when
prepared in 0.9% NaCl versus 5% glucose (p < 0.001; n = 6-7) and in dobutamine
when prepared in 0.9% NaCl (p < 0.001; n = 6-7). No differences in the
concentration of dopamine prepared in 0.9% NaCl were observed after 24 h in light
exposed and light-protected extension sets (n = 6-7). CONCLUSIONS: Dobutamine is
more stable in dilution vehicles than dopamine, and inotropes are more stable in
the 5% glucose dilution vehicle than in 0.9% NaCl. Such findings will provide
guidance on the choice of inotropes.
PMID- 28516290
TI - Comparison of Long-Term Outcomes After Non-curative Endoscopic Resection in Older
Patients with Early Gastric Cancer.
AB - BACKGROUND: Limited data exist that describe the long-term outcomes from
additional surgery following non-curative endoscopic resection (ER) of early
gastric cancer (EGC) in older people. This study aimed to determine the
appropriate treatment strategy for these patients. METHODS: We analyzed data from
2895 patients who underwent ER for EGC, of whom 451 (15.6%) had non-curative
resections followed by curative surgery or surveillance only. Of these patients,
138 were older (aged >=70 years). We compared the long-term outcomes of the
different treatment strategies in the older patients with non-curative resections
for EGC, and the outcomes of each treatment strategy, with those in younger
patients. RESULTS: The older patients underwent curative resections, non-curative
resections with surgery, or non-curative resections with surveillance, and the 5
year disease-specific survival (DSS) rates were 100, 100, and 73%, respectively.
There was a trend toward significance for DSS in favor of the non-curative
resections with surgery group compared with the non-curative resections with
surveillance-only group (p = 0.069). Among those who did not undergo additional
surgery, the older patients had worse DSS than the younger patients, and patients
who underwent additional surgery had better DSS, irrespective of their ages.
Multivariable analysis adjusted for other-cause mortality generated similar
results. Overall survival and recurrence-free survival did not differ according
to treatment strategy, and perioperative morbidity and mortality did not differ
significantly according to age. CONCLUSIONS: In older patients with non
curatively resected EGC, additional surgery demonstrated a trend toward better
DSS, and perioperative complications did not increase significantly.
PMID- 28516291
TI - Downstaging in Stage IV Pancreatic Cancer: A New Population Eligible for Surgery?
AB - BACKGROUND: Recent papers consider surgery as an option for synchronous liver
oligometastatic patients [metastatic pancreatic ductal adenocarcinoma (mPDAC)].
In this study, we present our series of resected mPDACs after neoadjuvant
chemotherapy (nCT). PATIENTS AND METHODS: All patients resected after downstaging
of mPDAC were included in this study. Downstaging criteria were disappearance of
liver metastasis and a decrease in cancer antigen (CA) 19-9. The type and
duration of nCT, last nCT surgery interval, histology, morbidity, and mortality
were recorded, and overall survival (OS) and disease-free survival (DFS) were
analyzed. RESULTS: Overall, 24 of 535 patients (4.5%) observed with mPDAC were
included. These patients received gemcitabine alone (5/24), gemcitabine +
nanoparticle albumin-bound (nab)-paclitaxel (3/24), and FOLFIRINOX (16/24).
Primary tumor size decreased from 31 to 19 mm (p < 0.001), and serum CA19-9
decreased from 596 to 18 U/mL (p < 0.001). In 14/24 patients, the tumor was
located in the head. Median interval nCT surgery was 2 months, there were no
mortalities, and the postoperative course was uneventful in 34% of cases. Grade
B/C pancreatic fistula, postoperative bleeding, and sepsis occurred in 17/4, 4,
and 12% of cases, respectively, and reoperation rate was 4%. R0 resection was
achieved in 88% of cases, with 17% complete pathological response. Positive nodes
were found in 9/24 patients with a median node ratio of 0.37, and OS and DFS was
56 and 27 months, respectively. CONCLUSIONS: Patients with mPDAC who were fully
responsive to nCT may be cautiously considered for surgery, with potential
benefit in survival compared with palliative chemotherapy alone. This is
supported by results of our retrospective study, which is the largest ever
reported.
PMID- 28516292
TI - LiMAx Test Improves Diagnosis of Chemotherapy-Associated Liver Injury Before
Resection of Colorectal Liver Metastases.
AB - BACKGROUND: Chemotherapy of colorectal liver metastases (CLMs) prior to liver
resection implies the risk of chemotherapy-associated liver injury, leading to
increased postoperative morbidity and mortality OBJECTIVE: The aim of this study
was to evaluate the LiMAx (liver maximum capacity) test for diagnosis of
chemotherapy-associated liver injury. METHODS: This was a retrospective analysis
of patients with CLMs, prior to liver resection. We performed preoperative
assessment of liver function using biochemical parameters and the LiMAx test. The
individual history of chemotherapy within 12 months, including regimen, number of
cycles, and therapy-free interval were collected, and histopathological
evaluation of tumor-free liver tissue was performed in resected patients.
RESULTS: A total of 204 patients were included, of whom 127 (62%) had received
previous chemotherapy. The LiMAx test was worse after chemotherapy (340 +/- 95
vs. 391 +/- 82 ug/kg/h; p < 0.001). Impaired LiMAx results (<315 ug/kg/h) were
determined in 49% of patients after chemotherapy, and no effects of chemotherapy,
liver steatosis or fibrosis on biochemical parameters were observed. LiMAx
impairment was dependent on the number of oxaliplatin cycles, the therapy-free
interval, and obesity in multivariate analysis. In addition, the LiMAx test was
worse in patients with relevant steatosis, fibrosis and steatohepatitis. Patients
with an impaired LiMAx showed sufficient regeneration during chemotherapy
cessation when surgery was postponed (272 +/- 57 - 348 +/- 72 ug/kg/h; p =
0.003). CONCLUSION: The LiMAx test enables non-invasive preoperative diagnosis of
chemotherapy-associated liver injury. Preoperative performance of the LiMAx test
can augment surgical strategy and timing of surgery after previous chemotherapy,
thus avoiding increased postoperative morbidity.
PMID- 28516294
TI - Does seeing an Asian face make speech sound more accented?
AB - Prior studies have reported that seeing an Asian face makes American English
sound more accented. The current study investigates whether this effect is
perceptual, or if it instead occurs at a later decision stage. We first
replicated the finding that showing static Asian and Caucasian faces can shift
people's reports about the accentedness of speech accompanying the pictures. When
we changed the static pictures to dubbed videos, reducing the demand
characteristics, the shift in reported accentedness largely disappeared. By
including unambiguous items along with the original ambiguous items, we
introduced a contrast bias and actually reversed the shift, with the Asian-face
videos yielding lower judgments of accentedness than the Caucasian-face videos.
By changing to a mixed rather than blocked design, so that the ethnicity of the
videos varied from trial to trial, we eliminated the difference in accentedness
rating. Finally, we tested participants' perception of accented speech using the
selective adaptation paradigm. After establishing that an auditory-only accented
adaptor shifted the perception of how accented test words are, we found that no
such adaptation effect occurred when the adapting sounds relied on visual
information (Asian vs. Caucasian videos) to influence the accentedness of an
ambiguous auditory adaptor. Collectively, the results demonstrate that visual
information can affect the interpretation, but not the perception, of accented
speech.
PMID- 28516295
TI - Judgments of differences and ratios of subjective heaviness.
AB - Experimental instructions to judge differences or ratios of subjective heaviness
numerically are generally assumed to produce judgments linearly proportional to
the respective heaviness differences or heaviness ratios. In this study,
participants were instructed to numerically judge the difference or ratio of
heaviness between two weights being lifted separately, either unimanually or
bimanually. Weight values were combined factorially. Patterns of factorial curves
revealed that unimanual lifting triggered linear judgments of heaviness
differences, whereas bimanual lifting triggered nonlinear judgments of heaviness
ratios. Lifting conditions produced these judgments independently of the
instruction specifications to judge differences or ratios. These results suggest
the interpretation that unimanual lifting triggers linear judgments of heaviness
differences by default, whereas bimanual lifting triggers nonlinear judgments of
heaviness ratios learned through experience. Implications for sensory measurement
are noted.
PMID- 28516293
TI - The dominant allele Aft induces a shift from flavonol to anthocyanin production
in response to UV-B radiation in tomato fruit.
AB - MAIN CONCLUSION: The introgression of the A ft allele into domesticated tomato
induced a shift from flavonol to anthocyanin production in response to UV-B
radiation, while the hp - 1 allele negatively influenced the response of
flavonoid biosynthesis to UV-B. Introgression of the dominant allele Anthocyanin
fruit (Aft) from Solanum chilense induces anthocyanin accumulation in the peel of
tomato (Solanum lycopersicum L.) fruit. UV-B radiation can influence plant
secondary metabolism regulating the expression of several genes, among which
those involved in flavonoid biosynthesis. Here, we investigated whether post
harvest UV-B treatment could up-regulate flavonoid production in tomato fruits
and whether the Aft allele could affect flavonoid biosynthesis under UV-B
radiation. Mature green fruits of an anthocyanin-rich tomato mutant line (SA206)
and of its wild-type reference, cv. Roma, were daily subjected to post-harvest UV
B treatment until full ripening. Up-regulation of CHS and CHI transcription by UV
B treatment induced flavonoid accumulation in the peel of cv. Roma. Conversely,
UV-B decreased the total flavonoid content and CHS transcript levels in the SA206
peel. SA206 being a double mutant containing also hp-1 allele, we investigated
also the behavior of hp-1 fruit. The decreased peel flavonoid accumulation and
gene transcription in response to UV-B suggest that hp-1 allele is involved in
the marked down-regulation of the flavonoid biosynthesis observed in SA206 fruit.
Interestingly, in SA206, UV-B radiation promoted the synthesis of delphinidin,
petunidin, and malvidin by increasing F3'5'H and DFR transcription, but it
decreased rutin production, suggesting a switch from flavonols to anthocyanins.
Finally, although UV-B radiation does not reach the inner fruit tissues, it down
regulated flavonoid biosynthesis in the flesh of both genotypes. This study
provides, for the first time, evidence that the presence of the functional Aft
allele, under UV-B radiation, redirects flavonoid synthesis towards anthocyanin
production and suggests that the hp-1 allele negatively influences the response
of flavonoid biosynthesis to UV-B.
PMID- 28516296
TI - Substrate-Coated Illumination Droplet Spray Ionization: Real-Time Monitoring of
Photocatalytic Reactions.
AB - Real-time monitoring of photocatalytic reactions facilitates the elucidation of
the mechanisms of the reactions. However, suitable tools for real-time monitoring
are lacking. Herein, a novel method based on droplet spray ionization named
substrate-coated illumination droplet spray ionization (SCI-DSI) for direct
analysis of photocatalytic reaction solution is reported. SCI-DSI addresses many
of the analytical limitations of electrospray ionization (ESI) for analysis of
photocatalytic-reaction intermediates, and has potential for both in situ
analysis and real-time monitoring of photocatalytic reactions. In SCI-DSI-mass
spectrometry (MS), a photocatalytic reaction occurs by loading sample solutions
onto the substrate-coated cover slip and by applying UV light above the modified
slip; one corner of this slip adjacent to the inlet of a mass spectrometer is the
high-electric-field location for launching a charged-droplet spray. After both
testing and optimizing the performance of SCI-DSI, the value of this method for
in situ analysis and real-time monitoring of photocatalytic reactions was
demonstrated by the removal of cyclophosphamide (CP) in TiO2/UV. Reaction times
ranged from seconds to minutes, and the proposed reaction intermediates were
captured and identified by tandem mass spectrometry. Moreover, the free hydroxyl
radical (.OH) was identified as the main radicals for CP removal. These results
show that SCI-DSI is suitable for in situ analysis and real-time monitoring of CP
removal under TiO2-based photocatalytic reactions. SCI-DSI is also a potential
tool for in situ analysis and real-time assessment of the roles of radicals
during CP removal under TiO2-based photocatalytic reactions.Graphical Abstract.
PMID- 28516299
TI - IPCAI 2017 Special Issue: Information Processing for Computer-Assisted
Interventions, 8th International Conference 2017-Part 1.
PMID- 28516297
TI - Subcritical Water Hydrolysis of Peptides: Amino Acid Side-Chain Modifications.
AB - Previously we have shown that subcritical water may be used as an alternative to
enzymatic digestion in the proteolysis of proteins for bottom-up proteomics.
Subcritical water hydrolysis of proteins was shown to result in protein sequence
coverages greater than or equal to that obtained following digestion with
trypsin; however, the percentage of peptide spectral matches for the samples
treated with trypsin were consistently greater than for those treated with
subcritical water. This observation suggests that in addition to cleavage of the
peptide bond, subcritical water treatment results in other hydrolysis products,
possibly due to modifications of amino acid side chains. Here, a model peptide
comprising all common amino acid residues (VQSIKCADFLHYMENPTWGR) and two further
model peptides (VCFQYMDRGDR and VQSIKADFLHYENPTWGR) were treated with subcritical
water with the aim of probing any induced amino acid side-chain modifications.
The hydrolysis products were analyzed by direct infusion electrospray tandem mass
spectrometry, either collision-induced dissociation or electron transfer
dissociation, and liquid chromatography collision-induced dissociation tandem
mass spectrometry. The results show preferential oxidation of cysteine to
sulfinic and sulfonic acid, and oxidation of methionine. In the absence of
cysteine and methionine, oxidation of tryptophan was observed. In addition, water
loss from aspartic acid and C-terminal amidation were observed in harsher
subcritical water conditions. Graphical Abstract ?.
PMID- 28516298
TI - Modeled traffic noise at the residence and colorectal cancer incidence: a cohort
study.
AB - PURPOSE: Traffic noise has become an increasing public health concern, associated
with pervasive negative health effects, most likely through pathways of sleep
disruption and stress. Both sleep disruption and stress have been associated with
colorectal cancer. The purpose of this study was to investigate the association
between residential traffic noise and colorectal cancer incidence. METHODS:
Traffic noise was calculated for all residential addresses from 1987 to 2012 for
51,283 Danes in the Diet, Cancer and Health Cohort. We used Cox proportional
hazard models to investigate the association between residential traffic noise 5
and 10 years before diagnosis, and overall colorectal cancer incidence, as well
as subtypes (rectal, proximal, and distal colon). Hazard ratios (HRs) were
calculated as crude and adjusted for potential confounders. RESULTS: During
follow-up, 1,134 colorectal cancers developed (737 colon, 397 rectal). We found
no association between residential road traffic noise and rectal cancer. We
observed an association with distal colon cancer: HR 1.18, 95% CI 1.00-1.40, but
not for proximal colon cancer: 0.99 (0.83-1.18), per 10 dB, 10 years preceding
diagnosis. There was no association between railway noise and colorectal cancer,
or any subtype. CONCLUSION: The present study suggested that long-term exposure
to residential road traffic noise might increase the risk for colon cancer,
especially distal colon cancer.
PMID- 28516300
TI - Predicting surgical skill from the first N seconds of a task: value over task
time using the isogony principle.
AB - PURPOSE: Most evaluations of surgical workflow or surgeon skill use simple,
descriptive statistics (e.g., time) across whole procedures, thereby
deemphasizing critical steps and potentially obscuring critical inefficiencies or
skill deficiencies. In this work, we examine off-line, temporal clustering
methods that chunk training procedures into clinically relevant surgical tasks or
steps during robot-assisted surgery. METHODS: Features calculated from the
isogony principle are used to train four common machine learning algorithms from
dry-lab laparoscopic data gathered from three common training exercises. These
models are used to predict the binary or ternary skill level of a surgeon. K-fold
and leave-one-user-out cross-validation are used to assess the accuracy of the
generated models. RESULTS: It is shown that the proposed scalar features can be
trained to create 2-class and 3-class classification models that map to
fundamentals of laparoscopic surgery skill level with median 85 and 63% accuracy
in cross-validation, respectively, for the targeted dataset. Also, it is shown
that the 2-class models can discern class at 90% of best-case mean accuracy with
only 8 s of data from the start of the task. CONCLUSION: Novice and expert skill
levels of unobserved trials can be discerned using a state vector machine trained
with parameters based on the isogony principle. The accuracy of this
classification comes within 90% of the classification accuracy from observing the
full trial within 10 s of task initiation on average.
PMID- 28516303
TI - Erratum to: Theoretical study of the H + HCN -> H + HNC process.
PMID- 28516302
TI - The minimally acceptable classification criterion for surgical skill: intent
vectors and separability of raw motion data.
AB - PURPOSE: Minimally invasive surgery requires objective methods for skill
evaluation and training. This work presents the minimally acceptable
classification (MAC) criterion for computational surgery: Given an obvious novice
and an obvious expert, a surgical skill evaluation classifier must yield 100%
accuracy. We propose that a rigorous motion analysis algorithm must meet this
minimal benchmark in order to justify its cost and use. METHODS: We use this
benchmark to investigate two concepts: First, how separable is raw,
multidimensional dry laboratory laparoscopic motion data between obvious novices
and obvious experts? We utilized information theoretic techniques to analytically
address this. Second, we examined the use of intent vectors to classify surgical
skill using three FLS tasks. RESULTS: We found that raw motion data alone are not
sufficient to classify skill level; however, the intent vector approach is
successful in classifying surgical skill level for certain tasks according to the
MAC criterion. For a pattern cutting task, this approach yields 100% accuracy in
leave-one-user-out cross-validation. CONCLUSION: Compared to prior art, the
intent vector approach provides a generalized method to assess laparoscopic
surgical skill using basic motion segments and passes the MAC criterion for some
but not all FLS tasks.
PMID- 28516301
TI - Application fields for the new Object Management Group (OMG) Standards Case
Management Model and Notation (CMMN) and Decision Management Notation (DMN) in
the perioperative field.
AB - PURPOSE: Medical processes can be modeled using different methods and notations.
Currently used modeling systems like Business Process Model and Notation (BPMN)
are not capable of describing the highly flexible and variable medical processes
in sufficient detail. METHODS: We combined two modeling systems, Business Process
Management (BPM) and Adaptive Case Management (ACM), to be able to model non
deterministic medical processes. We used the new Standards Case Management Model
and Notation (CMMN) and Decision Management Notation (DMN). RESULTS: First, we
explain how CMMN, DMN and BPMN could be used to model non-deterministic medical
processes. We applied this methodology to model 79 cataract operations provided
by University Hospital Leipzig, Germany, and four cataract operations provided by
University Eye Hospital Tuebingen, Germany. Our model consists of 85 tasks and
about 20 decisions in BPMN. We were able to expand the system with more complex
situations that might appear during an intervention. CONCLUSION: An effective
modeling of the cataract intervention is possible using the combination of BPM
and ACM. The combination gives the possibility to depict complex processes with
complex decisions. This combination allows a significant advantage for modeling
perioperative processes.
PMID- 28516304
TI - Strategy for designing stable and powerful nitrogen-rich high-energy materials by
introducing boron atoms.
AB - One of the most important aims in the development of high-energy materials is to
improve their stability and thus ensure that they are safe to manufacture and
transport. In this work, we theoretically investigated open-chain N4B2 isomers
using density functional theory in order to find the best way of stabilizing
nitrogen-rich molecules. The results show that the boron atoms in these isomers
are aligned linearly with their neighboring atoms, which facilitates close
packing in the crystals of these materials. Upon comparing the energies of nine
N4B2 isomers, we found that the structure with alternating N and B atoms had the
lowest energy. Structures with more than one nitrogen atom between two boron
atoms had higher energies. The energy of N4B2 increases by about 50 kcal/mol each
time it is rearranged to include an extra nitrogen atom between the two boron
atoms. More importantly, our results also show that boron atoms stabilize
nitrogen-rich molecules more efficiently than carbon atoms do. Also, the
combustion of any isomer of N4B2 releases more heat than the corresponding isomer
of N4C2 does under well-oxygenated conditions. Our study suggests that the three
most stable N4B2 isomers (BN13, BN24, and BN34) are good candidates for high
energy molecules, and it outlines a new strategy for designing stable boron
containing high-energy materials. Graphical abstract The structural
characteristics, thermodynamic stabilities, and exothermic properties of nitrogen
rich N4B2 isomers were investigated by means of density functional theory.
PMID- 28516305
TI - Arsenic toxicity and epimutagenecity: the new LINEage.
AB - Global methylation pattern regulates the normal functioning of a cell. Research
have shown arsenic alter these methylation landscapes within the genome leading
to aberrant gene expression and inducts various pathophysiological outcomes. Long
interspersed nuclear elements (LINE-1) normally remains inert due to heavy
methylation of it's promoters, time and various environmental insults, they lose
these methylation signatures and begin retro-transposition that has been
associated with genomic instability and cancerous outcomes. Of the various high
throughput technologies available to detect global methylation profile,
development of LINE-1 methylation index shall provide a cost effect-screening
tool to detect epimutagenic events in the wake of toxic exposure in a large
number of individuals. In the present review, we tried to discuss the state of
research and whether LINE-1 methylation can be considered as a potent epigenetic
signature for arsenic toxicity.
PMID- 28516306
TI - Peritoneal metastasis from pancreatic cancer treated with pressurized
intraperitoneal aerosol chemotherapy (PIPAC).
AB - Patients with peritoneal metastasis (PM) from pancreatic cancer have a short life
expectancy. Systemic combination chemotherapy leads to a median overall survival
of 7-8 months. Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is a
treatment alternative, where studies in patients with PM from ovarian, gastric
and colorectal cancer show a high safety profile and interesting results. This
case study report data on the PIPAC treatment in patients with PM from pancreatic
cancer. In a standard laparoscopy, chemotherapeutics (cisplatin and doxorubicin)
are nebulized within the peritoneal cavity. After 30 min, the chemotherapeutics
are evacuated through a closed system. The PIPAC procedure is repeated every 4-6
weeks. Five patients with PM from pancreatic cancer were treated with a total of
16 PIPAC procedures. All patients received >1 PIPAC and were eligible for
evaluation of histological regression. Four patients demonstrated histological
regression, and one patient had stable disease. Three patients are still alive,
and the median overall survival is 14 months (range 10-20) since the diagnosis of
PM. The histological regression and survival figures in this pilot study suggest
activity of PIPAC with low-dose cisplatin and doxorubicin in pretreated
peritoneal metastasis of pancreatic origin. This should now be evaluated in
prospective studies.
PMID- 28516307
TI - Appropriate control time constant in relation to characteristics of the
baroreflex vascular system in 1/R control of the total artificial heart.
AB - 1/R control is a physiological control method of the total artificial heart (TAH)
with which long-term survival was obtained with animal experiments. However, 1/R
control occasionally diverged in the undulation pump TAH (UPTAH) animal
experiment. To improve the control stability of the 1/R control, appropriate
control time constant in relation to characteristics of the baroreflex vascular
system was investigated with frequency analysis and numerical simulation. In the
frequency analysis, data of five goats in which the UPTAH was implanted were
analyzed with first Fourier transform technique to examine the vasomotion
frequency. The numerical simulation was carried out repeatedly changing
baroreflex parameters and control time constant using the elements-expanded
Windkessel model. Results of the frequency analysis showed that the 1/R control
tended to diverge when very low frequency band that was an indication of the
vasomotion frequency was relative high. In numerical simulation, divergence of
the 1/R control could be reproduced and the boundary curves between the
divergence and convergence of the 1/R control varied depending on the control
time constant. These results suggested that the 1/R control tended to be unstable
when the TAH recipient had high reflex speed in the baroreflex vascular system.
Therefore, the control time constant should be adjusted appropriately with the
individual vasomotion frequency.
PMID- 28516308
TI - The Charlie Sheen Effect on Rapid In-home Human Immunodeficiency Virus Test
Sales.
AB - One in eight of the 1.2 million Americans living with human immunodeficiency
virus (HIV) are unaware of their positive status, and untested individuals are
responsible for most new infections. As a result, testing is the most cost
effective HIV prevention strategy and must be accelerated when opportunities are
presented. Web searches for HIV spiked around actor Charlie Sheen's HIV-positive
disclosure. However, it is unknown whether Sheen's disclosure impacted offline
behaviors like HIV testing. The goal of this study was to determine if Sheen's
HIV disclosure was a record-setting HIV prevention event and determine if Web
searches presage increases in testing allowing for rapid detection and reaction
in the future. Sales of OraQuick rapid in-home HIV test kits in the USA were
monitored weekly from April 12, 2014, to April 16, 2016, alongside Web searches
including the terms "test," "tests," or "testing" and "HIV" as accessed from
Google Trends. Changes in OraQuick sales around Sheen's disclosure and prediction
models using Web searches were assessed. OraQuick sales rose 95% (95% CI, 75-117;
p < 0.001) of the week of Sheen's disclosure and remained elevated for 4 more
weeks (p < 0.05). In total, there were 8225 more sales than expected around
Sheen's disclosure, surpassing World AIDS Day by a factor of about 7. Moreover,
Web searches mirrored OraQuick sales trends (r = 0.79), demonstrating their
ability to presage increases in testing. The "Charlie Sheen effect" represents an
important opportunity for a public health response, and in the future, Web
searches can be used to detect and act on more opportunities to foster prevention
behaviors.
PMID- 28516309
TI - Assessing the Process of Retirement: a Cross-Cultural Review of Available
Measures.
AB - Retirement research is now expanding beyond the post-World War II baby boomers'
retirement attitudes and plans to include the nature of their workforce exit and
how successfully they adjust to their new life. These elements are collectively
known as the process of retirement. However, there is insufficient research in
developing countries to inform the management of their ageing populations
regarding this process. This review aims to facilitate national and cross
cultural research in developing and non-English speaking countries by reviewing
the existing measures of the retirement process published in English and
Portuguese. The review identified 28 existing measures assessing retirement
attitudes, planning, decision making, adjustment and satisfaction with
retirement. Information on each scale's item structure, internal reliability,
grammatical structure and evidence of translations to other languages is
presented. Of the 28 measures, 20 assessed retirement attitudes, plans and
decision-making, 5 assessed adjustment to retirement and only two assessed
retirement satisfaction. Only eight of the 28 scales had been translated into
languages other than English. There is scope to translate measures of retirement
attitudes and planning into other languages. However there is a paucity of
translated measures of retirement decision-making and adjustment, and measures of
retirement satisfaction in general. Within the limitations of this review,
researchers are provided with the background to decide between translating
existing measures or developing of more culturally appropriate assessment tools
for addressing their research questions.
PMID- 28516310
TI - Natural History of Patients Followed Radiographically with Mucinous Cysts of the
Pancreas.
AB - OBJECTIVE: The aim of this study was to evaluate the outcome of patients presumed
to have mucinous cysts of the pancreas who were initially selected for
radiographic surveillance. METHODS: Patients with a pancreatic cyst and a
measured cyst fluid carcinoembryonic antigen (CEA) >=192 ng/mL were included.
Patients were stratified by those who underwent initial resection and those who
were recommended for radiographic surveillance. The natural history of these two
groups was examined. RESULTS: From 1999 to 2014, 227 patients were identified who
had a cyst fluid CEA >=192 ng/mL (median 961, range 192-300,000 ng/mL). Immediate
resection was performed on 63 patients (28%). Initial radiographic surveillance
was recommended for 164 patients; 87% did not have main pancreatic duct dilation,
and 87% met consensus criteria for radiographic surveillance. After a median
follow-up of 56 months, 48 of the 164 patients (29%) had undergone resection.
Ultimately, there were three cases (2%) of high-grade dysplasia and two cases of
invasive carcinoma (1%) within these 164 patients selected for observation. Three
of the five cases of either high-grade dysplasia or invasive carcinoma were among
the 22 patients followed outside of consensus guidelines. CONCLUSIONS:
Appropriately selected patients with mucinous pancreatic cysts can be safely
followed with serial surveillance with a low risk of malignant progression.
PMID- 28516311
TI - Duodenal and Ampullary Carcinoid Tumors: Size Predicts Necessity for
Lymphadenectomy.
AB - BACKGROUND: Unlike other neuroendocrine tumors of the gastrointestinal tract,
management of duodenal and periampullary carcinoids remains controversial. We
aimed to determine the metastatic potential and optimal choice of therapy for
these neoplasms. METHODS: A retrospective review of all patients treated at the
Johns Hopkins Hospital between 1996 and 2012 was conducted. Clinicopathologic
factors associated with lymph nodal involvement and clinical outcomes were
evaluated. RESULTS: A total of 101 patients were identified. Eighty (79.2%)
tumors arose from the duodenum and 21 (20.8%) from the periampullary area. Thirty
five (34.7%) patients underwent pancreaticoduodenectomy (PD), 12 (11.9%) local
resection, 38 (37.6%) endoscopic excision, and 16 (15.8%) patients harbored
incidental tumors identified in the specimen after PD for another indication.
Lymph node (LN) pathologic evaluation was done in 56 patients, among which 27
(48%) had positive LN. Specifically, LN positivity (LN+) for tumors <1 cm in size
was 4.5% (1/22), for tumors 1-2 cm 72% (13/18), and for tumors >2 cm 81% (13/16).
Tumor size was the only factor associated with LN+ (p = 0.029). CONCLUSION: Lymph
nodal involvement is common for duodenal and periampullary carcinoid tumors,
particularly among those >1 cm in size; therefore, resection with
lymphadenectomyfor these larger tumors is recommended.
PMID- 28516312
TI - Macroinvertebrate Taxonomic and Functional Trait Compositions within Lotic
Habitats Affected By River Restoration Practices.
AB - The widespread degradation of lotic ecosystems has prompted extensive river
restoration efforts globally, but many studies have reported modest ecological
responses to rehabilitation practices. The functional properties of biotic
communities are rarely examined within post-project appraisals, which would
provide more ecological information underpinning ecosystem responses to
restoration practices and potentially pinpoint project limitations. This study
examines macroinvertebrate community responses to three projects which aimed to
physically restore channel morphologies. Taxonomic and functional trait
compositions supported by widely occurring lotic habitats (biotopes) were
examined across paired restored and non-restored (control) reaches. The
multivariate location (average community composition) of taxonomic and functional
trait compositions differed marginally between control and restored reaches.
However, changes in the amount of multivariate dispersion were more robust and
indicated greater ecological heterogeneity within restored reaches, particularly
when considering functional trait compositions. Organic biotopes (macrophyte
stands and macroalgae) occurred widely across all study sites and supported a
high alpha (within-habitat) taxonomic diversity compared to mineralogical
biotopes (sand and gravel patches), which were characteristic of restored
reaches. However, mineralogical biotopes possessed a higher beta (between
habitat) functional diversity, although this was less pronounced for taxonomic
compositions. This study demonstrates that examining the functional and
structural properties of taxa across distinct biotopes can provide a greater
understanding of biotic responses to river restoration works. Such information
could be used to better understand the ecological implications of rehabilitation
practices and guide more effective management strategies.
PMID- 28516314
TI - Harmonic subtraction for evaluating right ventricle ejection fraction from planar
equilibrium radionuclide angiography.
AB - We report an initial investigation of a subtraction-based method to estimate
right ventricle ejection fraction (RVEF) from ECG-gated planar equilibrium
radionuclide angiography (ERNA) data. Twenty-six consecutive patients referred
for scintigraphic evaluation of cardiac function prior to chemotherapy had ECG
gated first-pass (FP) imaging and ERNA imaging performed following the same
radiotracer injection. RVEF was computed from FP images (RVEFFP) and separately
from ERNA images (RVEFERNA). Standard methods for computing ejection fractions
were used to obtain RVEFFP values. RVEFERNA values were obtained using harmonic
subtraction of the left ventricular contribution from a biventricular region of
interest contoured on the equilibrium images acquired in the shallow right
anterior oblique projection. Clinically acquired chest CT data were used to
derive information regarding the relative position of the left and right
ventricle and about the presence of pulmonary artery enlargement. Computation of
RVEFERNA was successful for each of the 26 patients. Computation of RVEFFP failed
for four patients. For the 22 patients for which RVEF was computed using both
methods, the average RVEFFP was 49% and the average RVEFERNA was 51%, with
coefficients of variation of 11 and 7.5%, respectively. Low RVEFERNA values were
associated with pulmonary artery dilation. Estimation of RVEFERNA, using a
harmonic subtraction-based method of computation is clinically feasible and
accurate in the patient population studied. The results support further
investigation in patients with frank heart failure.
PMID- 28516313
TI - Dynamic changes in aortic impedance after transcatheter aortic valve replacement
and its impact on exploratory outcome.
AB - Valvulo-arterial impedance (Zva) has been shown to predict worse outcome in
medically managed aortic stenosis (AS) patients. We aimed to investigate the
association between Zva and left ventricular (LV) adaptation and to explore the
predictive value of Zva for cardiac functional recovery and outcome after
transcatheter aortic valve replacement (TAVR). We prospectively enrolled 128
patients with AS who underwent TAVR. Zva was calculated as: (systolic blood
pressure + mean transaortic gradient)/stroke volume index). Echocardiographic
assessment occurred at baseline, 1-month and 1-year after TAVR. The primary
endpoints were to investigate associations between Zva and global longitudinal
strain (GLS) at baseline as well as GLS change after TAVR. The secondary was to
compare all-cause mortality after TAVR between patients with pre-defined Zva (=5
mmHg m2/ml), stroke volume index (=35 ml/m2), and GLS (=-15%) cutoffs. The mean
GLS was reduced (-13.0 +/- 3.2%). The mean Zva was 5.2 +/- 1.6 mmHg*m2/ml with
55% of values >=5.0 mmHg*m2/ml, considered to be abnormally high. Higher Zva
correlated with worse GLS (r = -0.33, p < 0.001). After TAVR, Zva decreased
significantly (5.1 +/- 1.6 vs. 4.5 +/- 1.6 mmHg*m2/ml, p = 0.001). A reduction of
Zva at 1-month was associated with GLS improvement at 1-month (r = -0.31, p =
0.001) and at 1-year (r = -0.36 and p = 0.001). By Kaplan-Meier analysis,
patients with higher Zva at baseline had higher mortality (Log-rank p = 0.046),
while stroke volume index and GLS did not differentiate outcome (Log-rank p =
0.09 and 0.25, respectively). As a conclusion, Zva is correlated with GLS in AS
as well as GLS improvement after TAVR. Furthermore, a high baseline Zva may have
an additional impact to traditional parameters on predicting worse mortality
after TAVR.
PMID- 28516316
TI - Venous thromboembolism after nephrectomy: incidence, timing and associated risk
factors from a national multi-institutional database.
AB - PURPOSE: To evaluate the rate of venous thromboembolism (VTE) after nephrectomy
with specific focus on event timing and location (before or after hospital
discharge) in order to identify modifiable risk factors and establish benchmarks
for preventive interventions. METHODS: Using the ACS-NSQIP database, we
identified patients undergoing nephrectomy from 2006 to 2012. Patients were
analyzed in two cohorts: collectively and by surgical approach [open vs.
lap/robotic (MIS)]. Rates of deep vein thrombosis (DVT) and pulmonary embolus
(PE) were assessed and time to each event was established in relation to
discharge status. Logistic regression analysis was performed to assess
association between preoperative risk factors, surgical variables, and VTE.
RESULTS: In total, 13,208 patients met inclusion criteria. The overall rate of
VTE was 1.2% (PE = 0.5% and DVT = 0.8, 0.1% DVT and PE). Using regression
analysis, diabetes, dependent functional status, and longer operative time were
associated with higher odds of DVT. For PE, dyspnea, disseminated cancer, and
longer operative time were significant associations. The rate of VTE was higher
in open surgery compared to MIS (2 vs. 0.8%, p < 0.001). Median times to DVT and
PE were 8.5 and 6 days, respectively, with 53.3% of DVTs and 63.1% of PEs
occurring prior to discharge. CONCLUSIONS: The overall rate of VTE after
nephrectomy is low, occurs roughly one week after surgery, and is associated with
longer hospital stays. Certain patient factors, open surgical approach, and
longer operative times were associated with higher odds of post-operative VTE;
these patients may benefit from more aggressive prophylaxis.
PMID- 28516315
TI - "Finding the needle in a haystack": oncologic evaluation of patients treated for
LUTS with holmium laser enucleation of the prostate (HoLEP) versus transurethral
resection of the prostate (TURP).
AB - PURPOSE: To evaluate oncologic parameters of men with bothersome LUTS undergoing
surgical treatment with HoLEP or TURP. METHODS: Five hundred and eighteen
patients undergoing HoLEP (n = 289) or TURP (n = 229) were retrospectively
analyzed for total PSA, prostate volume, PSA density, history of prostate biopsy,
resected prostate weight, and histopathological features. Univariate and
multivariate logistic regression models were used to identify independent
predictors of incidental PCa (iPCa). RESULTS: Men undergoing HoLEP had a
significantly higher total PSA (median 5.5 vs. 2.3 ng/mL) and prostate volume
(median 80 vs. 41 cc), and displayed a greater reduction of prostate volume after
surgery compared to TURP patients (median 71 vs. 50%; all p < 0.001). With a
prevalence of incidental PCa (iPCa) of 15 and 17% for HoLEP and TURP,
respectively, the choice of procedure had no influence on the detection of iPCa
(p = 0.593). However, a higher rate of false-negative preoperative prostate
biopsies was noted among iPCa patients in the HoLEP arm (40 vs. 8%, p = 0.007).
In multivariate logistic regression, we identified patient age (OR 1.04; 95% CI
1.01-1.07, p = 0.013) and PSA density (OR 2.13; 95% CI 1.09-4.18, p = 0.028) as
independent predictors for the detection of iPCa. CONCLUSIONS: Despite
differences in oncologic parameters, the choice of technique had no influence on
the detection of iPCa. Increased patient age and higher PSA density were
associated with iPCa. A higher rate of false-negative preoperative prostate
biopsies was noted in HoLEP patients. Therefore, diagnostic assessment of LUTS
patients requires a more adapted approach to exclude malignancy, especially in
those with larger prostates.
PMID- 28516317
TI - CD95-CD95L interaction mediates the growth control of MHV68 immortalized B cells
by cytotoxic T cells.
PMID- 28516319
TI - Quantitative prediction of drug side effects based on drug-related features.
AB - MOTIVATION: Unexpected side effects of drugs are great concern in the drug
development, and the identification of side effects is an important task.
Recently, machine learning methods are proposed to predict the presence or
absence of interested side effects for drugs, but it is difficult to make the
accurate prediction for all of them. METHODS: In this paper, we transform side
effect profiles of drugs as their quantitative scores, by summing up their side
effects with weights. The quantitative scores may measure the dangers of drugs,
and thus help to compare the risk of different drugs. Here, we attempt to predict
quantitative scores of drugs, namely the quantitative prediction. Specifically,
we explore a variety of drug-related features and evaluate their discriminative
powers for the quantitative prediction. Then, we consider several feature
combination strategies (direct combination, average scoring ensemble combination)
to integrate three informative features: chemical substructures, targets, and
treatment indications. Finally, the average scoring ensemble model which produces
the better performances is used as the final quantitative prediction model.
RESULTS: Since weights for side effects are empirical values, we randomly
generate different weights in the simulation experiments. The experimental
results show that the quantitative method is robust to different weights, and
produces satisfying results. Although other state-of-the-art methods cannot make
the quantitative prediction directly, the prediction results can be transformed
as the quantitative scores. By indirect comparison, the proposed method produces
much better results than benchmark methods in the quantitative prediction. In
conclusion, the proposed method is promising for the quantitative prediction of
side effects, which may work cooperatively with existing state-of-the-art methods
to reveal dangers of drugs.
PMID- 28516318
TI - Effect of Apixaban on All-Cause Death in Patients with Atrial Fibrillation: a
Meta-Analysis Based on Imputed Placebo Effect.
AB - PURPOSE: Vitamin K antagonists (VKAs) are the standard of care for stroke
prevention in patients with atrial fibrillation (AF); therefore, there is not
equipoise when comparing newer oral anticoagulants with placebo in this setting.
METHODS: To explore the effect of apixaban on mortality in patients with AF, we
performed a meta-analysis of apixaban versus placebo using a putative placebo
analysis based on randomized controlled clinical trials that compared warfarin,
aspirin, and no antithrombotic control. We used data from two prospective
randomized controlled trials for our comparison of apixaban versus warfarin
(Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial
Fibrillation) and apixaban versus aspirin (Apixaban Versus Acetylsalicylic Acid
to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are
Unsuitable for Vitamin K Antagonist Treatment). Using meta-analysis approaches,
we indirectly compared apixaban with an imputed placebo with respect to the risk
of death in patients with AF. We used results from meta-analyses of randomized
trials as our reference for the comparison between warfarin and placebo/no
treatment, and aspirin and placebo/no treatment. RESULTS: In these meta-analyses,
a lower rate of death was seen both with warfarin (odds ratio [OR] 0.74, 95%
confidence interval [CI] 0.57-0.97) and aspirin (OR 0.86, 95% CI 0.69-1.07)
versus placebo/no treatment. Using data from ARISTOTLE and AVERROES, apixaban
reduced the risk of death by 34% (95% CI 12-50%; p = 0.004) and 33% (95% CI 6
52%; p = 0.02), respectively, when compared with an imputed placebo. The pooled
reduction in all-cause death with apixaban compared with an imputed placebo was
34% (95% CI 18-47%; p = 0.0002). CONCLUSIONS: In patients with AF, indirect
comparisons suggest that apixaban reduces all-cause death by approximately one
third compared with an imputed placebo.
PMID- 28516320
TI - How does the presence of a conspecific individual change the behavioral game that
a predator plays with its prey?
AB - Behavioral games predators play among themselves may have profound effects on
behavioral games predators play with their prey. We studied the behavioral game
between predators and prey within the framework of social foraging among
predators. We tested how conspecific interactions among predators (little egret)
change the predator-prey behavioral game and foraging success. To do so, we
examined foraging behavior of egrets alone and in pairs (male and female) in a
specially designed aviary consisting of three equally spaced pools with identical
initial prey (comet goldfish) densities. Each pool was comprised of a risky
microhabitat, rich with food, and a safe microhabitat with no food, forcing the
fish to trade off food and safety. When faced with two versus one egret, we found
that fish significantly reduced activity in the risky habitat. Egrets in pairs
suffered reduced foraging success (negative intraspecific density dependence) and
responded to fish behavior and to their conspecific by changing their visiting
regime at the different pools-having shorter, more frequent visits. The time
egret spent on each visit allowed them to match their long-term capture success
rate across the environment to their capture success rate in the pool, which
satisfies one aspect of optimality. Overall, egrets in pairs allocated more time
for foraging and changed their foraging tactics to focus more on fish under cover
and fish 'peeping' out from their shelter. These results suggest that both prey
and predator show behavioral flexibility and can adjust to changing conditions as
needed in this foraging game.
PMID- 28516321
TI - Evaluating local adaptation of a complex phenotype: reciprocal tests of pigmy
rattlesnake venoms on treefrog prey.
AB - Theory predicts that predator-prey interactions can generate reciprocal selection
pressures on species pairs, which can result in local adaptation, yet the
presence and pattern of local adaptation is poorly studied in vertebrate predator
prey systems. Here, we used a reciprocal common garden (laboratory) experimental
design involving comparisons between local and foreign populations to determine
if local adaptation was present between a generalist predator-the pigmy
rattlesnake (Sistrurus miliarius)-and a co-occurring prey-the squirrel treefrog
(Hyla squirella). We conducted toxicity trials using snake venom from two
populations separated by 340 km tested on prey from sympatric and allopatric
populations, resulting in data from four venom origin-frog origin combinations.
We assessed venom effectiveness using two measures (frog mortality at 24 h and
time to frog death) and then used regression analyses to look for a signal of
local adaptation with either measure. We found evidence for local adaptation for
one measure (time to death), but not the other (frog mortality). We argue that in
this system, the time to death of a prey item is a more ecologically relevant
measure of venom effectiveness than is frog mortality at 24 h. Our results
document an example of local adaptation between two interacting vertebrates using
a whole-organism assay and a local versus foreign criteria and provide evidence
that population-level variation in snake venom is adaptive.
PMID- 28516323
TI - Diffusion tensor imaging findings of the brainstem in subjects with tonsillar
ectopia.
AB - We aimed to evaluate the differences between apparent diffusion coefficient
(ADC), fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity
(RD) values obtained from different cranial sites in subjects with Chiari I
Malformation (CM-I) and borderline tonsillar ectopia (BTE), and to determine
correlations between diffusion tensor imaging (DTI) metrics and the severity of
tonsillar ectopia. A total of 73 subjects with CM-I and BTE and 35 control
underwent MRI and DTI. In our study, ADC values measured from the level of
medulla oblongata and the RD values measured in middle cerebellar peduncles,
thalamus, and globus pallidus were higher in CM-I patients than in controls. FA
values at the medulla oblongata level and AD values at the medulla oblongata and
pons level higher in patients with CM-I. ADC and AD values measured at the pons
level were higher in BTE subjects than in controls. Compared with BTE, the CM-I
subjects' ADC values at the medulla oblongata and AD values at the pons level
were higher. In addition, FAs at the pons and medulla oblongata level were
higher. At the medulla oblongata level, a positive correlation was observed
between ADC and the size of tonsillar ectopia. AD and FA values measured at the
level of medulla oblongata and pons were positively correlated with the size of
tonsillar ectopia. These findings may be related to the severity of
microstructural changes involving neuronal tracts at the brainstem level due to
tonsillar ectopia. DTI may be useful in determining the extent of microstructural
changes at the tissue level in subjects with tonsillar ectopia.
PMID- 28516322
TI - Do functional diversity and trait dominance determine carbon storage in an
altered tropical landscape?
AB - Altered landscapes play a major role in biodiversity conservation and carbon (C)
storage in the tropics. There is increasing evidence that C storage potential is
controlled by tree functional diversity, but underlying mechanisms are debated.
We analyzed the effects of trait dominance (mass-ratio hypothesis), species
diversity, and trait variation (species complementarity) on C storage in the
soils and vegetation of 20 agroforestry systems (AFS) and seven forested sites in
Costa Rica. AFS consisted of organic and conventional coffee farms and pastures
with trees. We used the community weighted mean (CWM) to measure trait dominance,
and functional divergence (FDvar) to evaluate trait variation of wood densities
(WD) and maximum heights (H max) of woody plants at each site. Species richness,
the number of woody plants per hectare, and slope of the terrain were also
considered as independent variables. Soil organic carbon (SOC) increased with
higher CWMWD and with higher variability of H max ([Formula: see text]) across
land-use types. Aboveground carbon (AGC) was controlled by the number of woody
plants per hectare and by species richness. Our results suggest that dominant
traits as well as species complementarity play an important role in determining C
storage. Diverse, multilayered AFS which incorporate trees with high WD, combined
with the conservation of remnant forests, can maximize C storage in the soils and
vegetation of altered tropical landscapes.
PMID- 28516326
TI - Capsule Commentary on Steinman et al., Epidemic Use of Benzodiazepines among
Older Adults in Israel: Epidemiology and Leverage Points for Improvement.
PMID- 28516325
TI - Capsule Commentary on Bennett et al., Engaging Stakeholders to Inform Clinical
Practice Guidelines that Address Multiple Chronic Conditions.
PMID- 28516324
TI - Bacterial intelligence: imitation games, time-sharing, and long-range quantum
coherence.
AB - Bacteria are far more intelligent than we can think of. They adopt different
survival strategies to make their life comfortable. Researches on bacterial
communication to date suggest that bacteria can communicate with each other using
chemical signaling molecules as well as using ion channel mediated electrical
signaling. Though in past few decades the scopes of chemical signaling have been
investigated extensively, those of electrical signaling have received less
attention. In this article, we present a novel perspective on time-sharing
behavior, which maintains the biofilm growth under reduced nutrient supply
between two distant biofilms through electrical signaling based on the
experimental evidence reported by Liu et al., in 2017. In addition, following the
recent work by Humphries et al. Cell 168(1):200-209, in 2017, we highlight the
consequences of long range electrical signaling within biofilm communities
through spatially propagating waves of potassium. Furthermore, we address the
possibility of two-way cellular communication between artificial and natural
cells through chemical signaling being inspired by recent experimental
observation (Lentini et al. 2017) where the efficiency of artificial cells in
imitating the natural cells is estimated through cellular Turing test. These
three spectacular observations lead us to envisage and devise new classical and
quantum views of these complex biochemical networks that have never been realized
previously.
PMID- 28516328
TI - Chronic traumatic encephalopathy: identifying those at risk and understanding
pathogenesis.
PMID- 28516327
TI - Long-term outcomes of epilepsy surgery in tuberous sclerosis complex.
AB - Approximately 50% of patients with tuberous sclerosis complex (TSC) present
intractable epilepsy, and surgery is an option for those patients. Hereby, we
analyze long-term seizure control and neuropsychological outcomes of epilepsy
surgery in patients with TSC. Clinical data were retrospectively collected from
66 patients with TSC and epilepsy followed up over 5 years, 51 of whom underwent
epilepsy surgery between 2001 and 2011. Reductions in the number of seizures were
analyzed at 1-year (1FU), 5-year (5FU), and 10-year (10FU) follow-ups visits
after the operation. Influential factors on postoperative seizure free and
intelligence quotient (IQ) and quality-of-life (QOL) outcomes were evaluated at
5FU. Resective procedures included 26 tuber resections, 15 lobectomies, and 10
tuber resections and lobectomies. Corpus callosotomies were performed as the
adjunctive approach in 11 cases with low IQ. The percentages of seizure-free
cases were 74.5% at 1FU, 58.8% at 5FU, and 47.8% at 10FU, and the predictive
factor for long-term postoperative seizure freedom was the history of
preoperative seizures and preoperative full-scale IQ. Significant improvements
were found in performance IQ, full-scale IQ, and QOL in patients from the surgery
group, particularly those who were seizure free after the operation. Our study
showed that epilepsy surgery in TSC with epilepsy rendered improvements in
seizure control, full-scale IQ, and QOL. Satisfactory long-term seizure control
was often achieved with an early operation and without mental retardation, and
improvements in QOL and IQ were frequently observed in postoperative patients who
remained seizure free.
PMID- 28516330
TI - Why antisense could make sense for neurodegeneration.
PMID- 28516329
TI - Screening for lipoprotein receptor-related protein 4-, agrin-, and titin
antibodies and exploring the autoimmune spectrum in myasthenia gravis.
AB - In autoimmune myasthenia gravis (MG), the identification of antibodies and
characterization of serological subgroups is of great importance for diagnosis
and management of the disease. Our aims were to study the frequency of antibodies
against lipoprotein-related protein 4 (LRP4), agrin, and titin using the most
recent techniques, and to characterize corresponding clinical features and
autoimmune diseases (AID) in 100 MG-patients. The antibody frequencies in the 55
AChR-antibody positive patients were 7% LRP4, 5% agrin, 53% titin, and in the 45
AChR-antibody negative patients 2% MuSK, 2% LRP4, 2% agrin, and 27% titin. LRP4
MG presented late-onset age, mild symptoms, good therapeutic response, and no
thymic changes. Agrin-MG showed early onset age, mild-to-severe symptoms, and
moderate treatment response. The phenotype of titin-MG depended on AChR
antibodies: AChR-antibody negative patients presented with mostly mild limb
muscle weakness, whereas AChR-antibody positive patients showed more frequently
severe symptoms, including myasthenic crisis, bulbar predominance, and thymoma.
Additional AID were detected in 32% of MG-patients, most frequently Hashimoto's
thyroiditis (21%). Based on our data, we recommend the detection of LRP4
antibodies for at least AChR-antibody negative MG-patients and titin-antibodies
for all MG-patients. We propose taking an accurate medical history for typical
symptoms of Hashimoto's thyroiditis in MG-patients.
PMID- 28516332
TI - Prevalence and mortality of patients with multiple sclerosis in France in 2012: a
study based on French health insurance data.
AB - Data on the prevalence of multiple sclerosis (MS) in France are scarce. National
and regional updated estimates are needed to better plan health policies. In this
nationwide study, we provided estimates of the prevalence of MS in France in 2012
and mortality rate in 2013. MS cases were identified in the French national
health insurance database (SNIIRAM-PMSI) using reimbursement data for disease
modifying treatment, long-term disease status for MS, disability pension for MS,
and hospitalisation for MS (MS ICD-10 code: G35). We identified 99,123 MS cases,
corresponding to an overall crude prevalence rate of 151.2 per 100,000
inhabitants [95% confidence interval (CI) 150.3-152.2]: 210.0 per 100,000 in
women (95% CI 208.4-211.5) and 88.7 per 100,000 in men (95% CI 87.6-89.7). The
overall prevalence rate was 155.6 per 100,000 inhabitants (95% CI 154.7-156.6)
after standardization on the 2013-European population. We observed a prevalence
gradient with a higher prevalence (190-200 per 100,000) in North-Eastern France
and a lower prevalence in Southern and Western France (126-140). The crude
mortality rate in 2013 was 13.7 per 1,000 MS cases (11.4 in women and 20.3 in
men). The standardized mortality ratio was 2.56 (95% CI 2.41-2.72). Our results
revise upwards the estimation of MS prevalence in France and confirm the excess
mortality of MS patients compared to the general population.
PMID- 28516331
TI - Burden of herpes simplex virus encephalitis in the United States.
AB - Herpes simplex virus encephalitis (HSVE) is a disease of public health concern,
but its burden on the healthcare of United States has not been adequately
assessed recently. We aimed to define the incidence, complications and outcomes
of HSVE in the recent decade by analyzing data from a nationally representative
database. Healthcare Cost and Utilization Project databases were utilized to
identify patients with primary discharge diagnosis of HSVE. Annual
hospitalization rate was estimated and several preselected inpatient
complications were identified. Regression analyses were used to identify
mortality predictors. Key epidemiological factors were compared with those from
other countries. Total 4871 patients of HSVE were included in our study. The
annual hospitalization rate was 10.3 +/- 2.2 cases/million in neonates, 2.4 +/-
0.3 cases/million in children and 6.4 +/- 0.4 cases/million in adults. Median age
was 57 years and male:female incidence ratio was 1:1. Rates of some central
nervous system complications were seizures (38.4%), status epilepticus (5.5%),
acute respiratory failure (20.1%), ischemic stroke (5.6%) and intracranial
hemorrhage (2.7%), all of which were significantly associated with mortality. In
hospital mortality in neonates, children and adults were 6.9, 1.2 and 7.7%,
respectively. HSVE still remains a potentially lethal infectious disease with
high morbidity and mortality. Most recent epidemiological data in this study may
help understanding this public health disease, and the patient outcome data may
have prognostic significance.
PMID- 28516333
TI - Risk of Hip Fracture in Older People Using Selective Serotonin Reuptake
Inhibitors and Other Psychoactive Medicines Concurrently: A Matched Case-Control
Study in Australia.
AB - BACKGROUND: Few studies have assessed the risk of hip fracture following
concurrent use of psychoactive medicines, and none has investigated combinations
with selective serotonin reuptake inhibitors. OBJECTIVES: To assess the risk of
hip fracture in older people as a result of concurrent use of selective serotonin
reuptake inhibitors and other psychoactive medicines. METHODS: A matched case
control design was employed. Cases were Australian Government Department of
Veterans' Affairs beneficiaries aged over 65 years who experienced a hip fracture
between 2009 and 2012. Each case was matched with up to four randomly selected
controls of the same age (+/-2 years) and sex. Medicine-hip fracture associations
were estimated via conditional logistic regression. The relative excess risk due
to interaction (RERI) was calculated to determine whether combined effects
differed from the sum of individual effects. RESULTS: There were 8828 cases and
35,310 controls. The median age of subjects was 88 years and 63% were women. The
risk of hip fracture was elevated for all medicines assessed individually, most
notably selective serotonin reuptake inhibitors (initiation: odds ratio [OR] =
2.7, 95% confidence interval [CI] 2.1, 3.6) and opioids (initiation: OR = 2.3,
95% CI 1.9, 2.9). Combinations associated with an increased odds of hip fracture
included addition of benzodiazepines to selective serotonin reuptake inhibitor
therapy (OR = 3.0, 95% CI 1.9, 4.8; RERI = 0.9, 95% CI -0.5, 2.3), concurrent use
of both opioids and selective serotonin reuptake inhibitors (OR = 2.2, 95% CI
1.9, 2.6; RERI = 0.1, 95% CI -0.3, 0.5), addition of opioids to selective
serotonin reuptake inhibitor therapy (OR = 3.2, 95% CI 1.8, 5.5; RERI = -0.1, 95%
CI -2.0, 1.7), and initiation of both benzodiazepines and selective serotonin
reuptake inhibitors (OR = 4.7, 95% CI 1.7, 13; RERI = 1.3, 95% CI -3.8, 6.3). The
RERI results suggested that the effect of each of these medicine combinations
equalled the sum of the effects of individual medicine use. CONCLUSIONS: In older
people, the concurrent use of selective serotonin reuptake inhibitors and other
psychoactive medicines increased the risk of hip fracture as much as the sum of
the risks owing to individual medicine use. Our results highlight the need for
prescribers to consider the sedative burden of medicines in each older patient as
well as the potential for an additive risk of hip fracture when initiating
additional psychoactive therapy.
PMID- 28516334
TI - In the Real-World, Kids Use Medications and Devices.
AB - In the real world, we lack evidence guiding the use of medications and devices in
children. This lack of evidence arose out of the challenges of conducting
clinical trials in children and other vulnerable populations and the historical
decision (reversed in recent decades) to exclude children from clinical trials.
The recent focus on the potential of real-world evidence (RWE) to guide approval
and use of new treatments may provide a much-needed solution. A broad definition
of RWE includes prospective observational data and data from electronic health
records and claims, as well as other sources. For the most part, it is reasonable
to expect that considerations around the use of RWE in adult populations will
apply to its use in children. However, a number of issues around the use of RWE
are unique to studying children. These fall into at least four categories: (1)
identification of databases with adequate numbers of children in the age sub
groups of interest, (2) access to critical variables such as birth date, birth
weight, and gestational age, (3) linkage to parental records for information
about pre-natal exposures, family history, and socio-economic status, and (4)
linkage to school records for information about outcomes such as missed school
days, academic progress, and behavioral issues. Addressing the needs of children
in developing methodologies for use of RWE ensures that ongoing efforts will
benefit children as well as other sectors of the population.
PMID- 28516337
TI - Mesoscopic organization in ionic liquids.
AB - We discuss some published results and provide new observations concerning the
high level of structural complexity that lies behind the nanoscale correlations
in ionic liquids (ILs) and their mixtures with molecular liquids. It turns out
that this organization is a consequence of the hierarchical construction on both
spatial (from angstrom to several nanometer) and temporal (from fraction of
picosecond to hundreds of nanosecond) scales, which requires joint use of
experimental and computational tools.
PMID- 28516335
TI - Prognostic value of pre-treatment 18F-FDG-PET uptake in small-cell lung cancer.
AB - PURPOSE: Small-cell lung cancer (SCLC) is an aggressive disease, despite an
initially favorable response to treatment, and its prognosis is still poor.
Multiple parameters have been studied as possible prognostic factors, but none of
them are reliable enough to change the treatment approach. 18F-fluorodeoxyglucose
positron emission tomography (FDG-PET) is a novel imaging technique for staging
of SCLC. The aim of this study was to evaluate the prognostic value of pre
treatment FDG-PET parameters on clinical outcome in limited stage (LS) SCLC
patients treated with curative thoracic radiotherapy (RT) and chemotherapy.
METHODS: Clinical records of 46 LS-SCLC patients with pre-treatment FDG-PET
imaging were retrospectively reviewed. Patients were treated with definitive RT
for a total dose of 50-60 Gy and chemotherapy. The clinical endpoints were
progression-free survival (PFS) and overall survival (OS). RESULTS: The median
age was 59 (range 30-82) years, and median follow-up time was 23.2 months (range
5-82.8 months). Median OS was 30.9 months for pre-treatment tumor maximum
standardized uptake value (SUVmax) <9.3 and 20.6 months for SUVmax >=9.3 (p =
0.027) and PFS was 55.6 months for SUVmax <9.3 and 38.6 months for SUVmax >=9.3
(p = 0.16). Median OS was 73 months for pre-treatment lymph node SUVmax <5.8 and
21 months for >=5.8 (p = 0.01) and PFS was 38.6 months (range 6.8-70.3 months)
for SUVmax-LN >=5.8; all patients with SUVmax-LN <5.8 were alive (p = 0.07).
Median survival time was 28.2 months (range 21.7-34.7 months) for patients
younger than 65 and 8.7 months (range 5.7-11.8 months) for those >=65 years (p =
0.00). CONCLUSIONS: Pre-treatment FDG-PET uptake may be a valuable tool to
evaluate prognosis in SCLC patients. Patients with a higher pre-treatment FDG
uptake may be considered at increased risk of failure and may benefit from more
aggressive treatment approaches.
PMID- 28516336
TI - Changes of functional connectivity of the anterior cingulate cortex in women with
primary dysmenorrhea.
AB - Primary dysmenorrhea (PDM), a common gynecological disorder, is associated with
structural and functional alterations in several subregions of the anterior
cingulate cortex (ACC). However, systematic functional connectivity of the ACC
subregions in PDM has not been clarified. In this study, we used resting-state
functional magnetic resonance imaging (fMRI) data from forty-eight PDM patients
and thirty-eight matched female healthy controls to investigate the functional
connectivity of ACC subregions in PDM. Compared to healthy controls, PDM patients
exhibited increased connectivity between the caudal ACC (cACC) and primary
somatosensory cortex (SI), between the perigenual ACC (pACC) and caudate, and
between the subgenual ACC (sACC) and medial prefrontal cortex (mPFC). PDM
patients also showed decreased connectivity between the pACC and precuneus. In
PDM group, the connectivity of the right pACC-right caudate positively correlated
with disease duration, and the connectivity of the left pACC-left precuneus
negatively correlated with disease severity. These present findings reveal that
abnormal ACC connectivity may be implicated in the PDM-related disturbances in
pain sensory, modulation, and affection. We hope that our study could enhance the
understanding of the pathophysiology underlying PDM.
PMID- 28516339
TI - Holding Manufacturers of Defective Firearms to Account: Does Restricting
Liability Lawsuits Violate the Second Amendment?
AB - Judicial and statutory developments since 2005 have placed considerable
roadblocks in the way of legal efforts against the epidemic of gun violence in
the United States. Although the Second Amendment is most often cited by those
opposed to gun control, it offers a potential opportunity to be invoked in
support of harm minimization.
PMID- 28516338
TI - Intergroup variation in robbing and bartering by long-tailed macaques at Uluwatu
Temple (Bali, Indonesia).
AB - Robbing and bartering (RB) is a behavioral practice anecdotally reported in free
ranging commensal macaques. It usually occurs in two steps: after taking inedible
objects (e.g., glasses) from humans, the macaques appear to use them as tokens,
returning them to humans in exchange for food. While extensively studied in
captivity, our research is the first to investigate the object/food exchange
between humans and primates in a natural setting. During a 4-month study in 2010,
we used both focal and event sampling to record 201 RB events in a population of
long-tailed macaques (Macaca fascicularis), including four neighboring groups
ranging freely around Uluwatu Temple, Bali (Indonesia). In each group, we
documented the RB frequency, prevalence and outcome, and tested the underpinning
anthropogenic and demographic determinants. In line with the environmental
opportunity hypothesis, we found a positive qualitative relation at the group
level between time spent in tourist zones and RB frequency or prevalence. For two
of the four groups, RB events were significantly more frequent when humans were
more present in the environment. We also found qualitative partial support for
the male-biased sex ratio hypothesis [i.e., RB was more frequent and prevalent in
groups with higher ratios of (sub)adult males], whereas the group density
hypothesis was not supported. This preliminary study showed that RB is a
spontaneous, customary (in some groups), and enduring population-specific
practice characterized by intergroup variation in Balinese macaques. As such, RB
is a candidate for a new behavioral tradition in this species.
PMID- 28516340
TI - Social studying and learning among medical students: a scoping review.
AB - INTRODUCTION: Medical students study in social groups, which influence their
learning, but few studies have investigated the characteristics of study groups
and the impacts they have on students' learning. A scoping review was conducted
on the topic of informal social studying and learning within medical education
with the aim of appraising what is known regarding medical student attitudes to
group study, the impact of group study on participants, and the methods that have
been employed to study this. METHODS: Using Arksey and O'Malley's scoping review
principles, MEDLINE, EMBASE and CINAHL were searched, along with hand-searching
and a targeted search of the grey literature; 18 peer reviewed and 17 grey
literature records were included. RESULTS: Thematic conceptual analysis
identified a number of themes, including: the nature of group study; the utility
and value of group studying including social learning facilitating student
engagement, social learning as a source of motivation and accountability, and
social learning as a source of wellbeing; and student preferences related to
group studying, including its homophilic nature, transgressiveness, and
effectiveness. Despite these emerging factors, the evidence base for this
phenomenon is small. DISCUSSION: The findings in this scoping review demonstrate
a clear role for social interaction outside of the classroom, and encourage us to
consider the factors in student networking, and the implications of this on
medical students' academics. We also highlight areas in need of future research
to allow us to better situate informal social learning within medical education
and to enable educators to support this phenomenon.
PMID- 28516341
TI - Fairness: the hidden challenge for competency-based postgraduate medical
education programs.
AB - Competency-based medical education systems allow institutions to individualize
teaching practices to meet the needs of diverse learners. Yet, the focus on
continuous improvement and individualization of curricula does not exempt
programs from treating learners in a fair manner. When learners fail to meet key
competencies and are placed on probation or dismissed from training programs,
issues of fairness may form the basis of their legal claims. In a literature
search, we found no in-depth examination of fairness. In this paper, we utilize a
systems lens to examine fairness within postgraduate medical education contexts,
focusing on educational opportunities, assessment practices, decision-making
processes, fairness from a legal standpoint, and fairness in the context of the
learning environment. While we provide examples of fairness issues within US
training programs, concerns regarding fairness are relevant in any medical
education system which utilizes a competency-based education framework.Assessment
oversight committees and annual programmatic evaluations, while recommended, will
not guarantee fairness within postgraduate medical education programs, but they
can provide a window into 'hidden' threats to fairness, as everything from
training experiences to assessment practices may be examined by these committees.
One of the first steps programs can take is to recognize that threats to fairness
may exist in any educational program, including their own, and begin
conversations about how to address these issues.
PMID- 28516342
TI - Pharmacokinetic Bioequivalence Studies of an Extended-Release Oxycodone
Hydrochloride Tablet in Healthy Japanese Subjects Under Fasting and Fed
Conditions Without an Opioid Antagonist.
AB - Oxycodone is a semisynthetic opioid used for the treatment of moderate to severe
pain. Two separate studies were conducted to assess the pharmacokinetic
bioequivalence of a newly formulated oxycodone hydrochloride extended-release
tablet to a marketed oxycodone product in Japan under fasting and fed conditions.
Each study was a randomized, open-label, single-dose, single-center, two-period,
two-way crossover study. Healthy male Japanese subjects received the oxycodone 10
mg products under fasting and fed conditions. Blood samples were collected at
specified time intervals, and plasma concentrations of oxycodone were analyzed
using a validated liquid chromatography tandem mass spectrometry assay method.
The pharmacokinetic parameters were determined via non-compartmental analysis.
Pharmacokinetic metrics used for bioequivalence assessment were the maximum
observed plasma concentration (C max) and the area under the concentration-time
curve up to the last sampling time (AUC t ). A total of 24 healthy subjects were
enrolled in each study. One subject withdrew after completion of the first
sequence under fed conditions. The ratios of geometric least square means for C
max and AUC t under fasting conditions were 1.1110 (90% confidence interval [CI]
1.0562-1.1687) and 0.9946 (90% CI 0.9670-1.0231), respectively. The ratios of
geometric least square means for C max and AUCt under fed conditions were 1.1417
(90% CI 1.0959-1.1895) and 1.0135 (90% CI 0.9810-1.0470), respectively. The 90%
CIs were within the predefined range (0.80-1.25). Both treatments were well
tolerated when taken without an opioid antagonist in healthy Japanese subjects.
Pharmacokinetic bioequivalence between test and reference formulations under
fasting and fed conditions was concluded in terms of both rate and extent of
absorption.
PMID- 28516343
TI - Therapeutic dormancy to delay postsurgical glioma recurrence: the past, present
and promise of focal hypothermia.
AB - Surgery precedes both radiotherapy and chemotherapy as the first-line therapy for
glioma. However, despite multimodal treatment, most glioma patients die from
local recurrence in the resection margin. Glioma surgery is inherently lesional,
and the response of brain tissue to surgery includes hemostasis, angiogenesis,
reactive gliosis and inflammation. Unfortunately, these processes are also
associated with tumorigenic side-effects. An increasing amount of evidence
indicates that the response to a surgery-related brain injury is hijacked by
residual glioma cells and participates in the local regeneration of tumor tissues
at the resection margin. Inducing therapeutic hypothermia in the brain has long
been used to treat the secondary damage, such as neuroinflammation and edema,
that are caused by accidental traumatic brain injuries. There is compelling
evidence to suggest that inducing therapeutic hypothermia at the resection margin
would delay the local recurrence of glioma by (i) limiting cell proliferation,
(ii) disrupting the pathological connection between inflammation and glioma
recurrence, and (iii) limiting the consequences of the functional heterogeneity
and complexity inherent to the tumor ecosystem. While the global whole-body
cooling methods that are currently used to treat stroke in clinical practice may
not adequately treat the resection margin, the future lies in implantable focal
microcooling devices similar to those under development for the treatment of
epilepsy. Preclinical and clinical strategies to evaluate focal hypothermia must
be implemented to prevent glioma recurrence in the resection margin. Placing the
resection margin in a state of hibernation may potentially provide such a long
awaited therapeutic breakthrough.
PMID- 28516345
TI - Performance and cost evaluation of health information systems using micro-costing
and discrete-event simulation.
AB - Innovation and health-care funding reforms have contributed to the deployment of
Information and Communication Technology (ICT) to improve patient care. Many
health-care organizations considered the application of ICT as a crucial key to
enhance health-care management. The purpose of this paper is to provide a
methodology to assess the organizational impact of high-level Health Information
System (HIS) on patient pathway. We propose an integrated performance evaluation
of HIS approach through the combination of formal modeling using the Architecture
of Integrated Information Systems (ARIS) models, a micro-costing approach for
cost evaluation, and a Discrete-Event Simulation (DES) approach. The methodology
is applied to the consultation for cancer treatment process. Simulation scenarios
are established to conclude about the impact of HIS on patient pathway. We
demonstrated that although high level HIS lengthen the consultation, occupation
rate of oncologists are lower and quality of service is higher (through the
number of available information accessed during the consultation to formulate the
diagnostic). The provided method allows also to determine the most cost-effective
ICT elements to improve the care process quality while minimizing costs. The
methodology is flexible enough to be applied to other health-care systems.
PMID- 28516344
TI - Defining optimal cutoff value of MGMT promoter methylation by ROC analysis for
clinical setting in glioblastoma patients.
AB - Resistance to temozolomide (TMZ) chemotherapy poses a significant challenge in
the treatment of glioblastoma (GBM). Hypermethylation in O6-methylguanine-DNA
methyltransferase (MGMT) promoter is thought to play a critical role in this
resistance. Pyrosequencing (PSQ) has been shown to be accurate and robust for
MGMT promoter methylation testing. The unresolved issue is the determination of a
cut-off value for dichotomization of quantitative MGMT PSQ results into "MGMT
methylated" and "MGMT unmethylated" patient subgroups as a basis for further
treatment decisions. In this study, receiver operating characteristic (ROC) curve
analysis was used to identify an optimal cutoff of MGMT promoter methylation by
testing mean percentage of methylation of 4 CpG islands (76-79) within MGMT exon
1. The area under the ROC (AUC) as well as the best cutoff to classify the
methylation were calculated. Positive likelihood ratio (LR+) was chosen as a
diagnostic parameter for defining an optimal cut-off. Meanwhile, we also analyzed
whether mean percentage of methylation at the investigated CpG islands could be
regarded as a marker for evaluating prognostication. ROC analysis showed that the
optimal threshold was 12.5% (sensitivity: 60.87%; specificity: 76%) in response
to the largest LR+ 2.54. 12.5% was established to distinguish MGMT promoter
methylation, which was confirmed using validation set. According to the cutoff
value, the MGMT promoter methylation was found in 58.3% of GBM. Mean methylation
level of the investigated CpG sites strong correlated with overall survival (OS),
which means GBM patients with a high level of methylation survived longer than
those with low level of methylation(log-rank test, P = 0.017). In conclusion, ROC
curve analysis enables the best cutoff for discriminating MGMT promoter
methylation status. LR+ can be used as a key factor that evaluates cutoff. The
promoter methylation level of MGMT by PSQ in GBM patients had prognostic value.
PMID- 28516346
TI - Site, Sector, Scope: Mapping the Epistemological Landscape of Health Humanities.
AB - This essay presents a critical appraisal of the current state of baccalaureate
Health Humanities, with a special focus on the contextual differences currently
influencing the implementation of this field in Canada and, to a lesser extent,
the United States and United Kingdom. I argue that the epistemological bedrock of
Health Humanities goes beyond that generated by its written texts to include
three external factors that are especially pertinent to undergraduate education:
site (the setting of Health Humanities education), sector (the disciplinary
eligibility for funding) and scope (the critical engagement with a program's
local context alongside an emergent "core" of Health Humanities knowledge,
learning, and practice). Drawing largely from the Canadian context, I discuss how
these differences can inform or obstruct this field's development, and offer
preliminary recommendations for encouraging the growth of baccalaureate Health
Humanities-in Canada and elsewhere-in light of these factors.
PMID- 28516347
TI - Uniting the Pre-Health Humanities with the Introductory Composition Course.
AB - Drawing on my experiences at a teaching-focused university, I show how locating
the health humanities in first-year or introductory composition courses improves
learning and offers an economical, flexible, and far-reaching approach to
bringing a health humanities education to all baccalaureate-level learners,
regardless of whether they aspire to careers in the health professions. In terms
of improving learning, health humanities composition courses support the
disciplinary aims of both fields. Accessible, relevant issues in the health
humanities, such as interventions in health debates or representations of illness
and healthcare settings, nourish the cognitive and social conditions needed to
develop college-level writing skills. The health humanities' emphases on
interdisciplinarity and suspending judgment also inform students' writing
abilities. Composition trains students to write rhetorically by considering
purpose, context, genre, mode, and other factors when addressing an audience.
This approach to writing helps pre-health humanists communicate intentionally and
compassionately about health topics as well as the larger issues they call into
question. Because students enroll in health humanities composition courses at an
early, formative moment in their studies, they are poised to carry or "transfer"
their knowledge to other courses, including those that might prepare them for the
workforce.
PMID- 28516348
TI - Sclerosing Mucoepidermoid Carcinoma of the Submandibular Gland Presenting as
Chronic Sialadenitis: A Case Report and Review of Literature.
AB - Sclerosing mucoepidermoid carcinoma of the salivary gland (SMEC) is a rare
subtype of mucoepidermoid carcinoma (MEC), first described in 1987 by Chan and
Saw. As far as we are aware, only 30 cases have been published since then. Most
cases were located in the parotid gland with some cases described in the
submandibular and minor salivary glands. SMEC typically presents as a long
standing mass, with a non-specific enhancing appearance on imaging and is often
non-diagnostic on fine needle aspiration, making pre-operative diagnosis very
difficult. It is characterised by dense sclerosis within an otherwise typical
MEC, frequently with lymphoid proliferation and eosinophils at the periphery. The
histological diagnosis of SMEC can be challenging, as the sclerosis may obscure
the other morphological features, which can lead to misdiagnosis. Grading can
also be difficult, and the prognostic value of grading for SMEC remains unclear.
Herein is described a new case of SMEC, presenting clinically as chronic
sialadenitis in the left submandibular gland of a 41 year old male. A brief
literature review and the issues surrounding diagnosis and grading are also
discussed.
PMID- 28516349
TI - Anthropogenic activities and coastal environmental quality: a regional
quantitative analysis in southeast China with management implications.
AB - Regional analysis of environmental issues has always been a hot topic in the
field of sustainable development. Because the different levels of economic
growth, urbanization, resource endowments, etc. in different regions generate
apparently different ecological responses, a better description and comparison
across different regions will provide more valuable implications for ecological
improvement and policymaking. In this study, seven typical bays in southeast
China that are a rapid developing area were selected to quantitatively analyze
the relationship between socioeconomic development and coastal environmental
quality. Based on the water quality data from 2007 to 2015, the multivariate
statistical method was applied to analyze the potential environmental risks and
to classify the seven bays based on their environmental quality status. The
possible variation trends of environmental indices were predicted based on the
cross-regional panel data by Environmental Kuznets Curve. The results showed that
there were significant regional differences among the seven bays, especially
Quanzhou, Xiamen, and Luoyuan Bays, suffered from severer artificial disturbances
than other bays, despite their different development patterns. Socioeconomic
development level was significantly associated with some water quality indices
(pH, DIN, PO4-P); the association was roughly positive: the areas with higher GDP
per capita have some worse water quality indices. In addition, the decreasing
trend of pH values and the increasing trend of nutrient concentration in the
seven bays will continue in the foreseeable future. In consideration of the
variation trends, the limiting nutrient strategy should be implemented to
mitigate the deterioration of the coastal environments.
PMID- 28516350
TI - Evaluation of vascular effect of arsenic using in vivo assays.
AB - Arsenic (As) is an abundant toxicant present in groundwater and soil in various
parts of the world including eastern part of India. The epidemiological studies
have shown that arsenic exposure is linked to developmental defects and
miscarriage. Placenta is known to utilize vasculogenesis to develop its
vasculature circulation. The effects of four different doses of sodium meta
arsenite (0, 10, 20, 75, and 150 ppm) were assessed on the vascular structure
using two different in vivo models, i.e., Matrigel and chorioallantoic membrane
(CAM) assay. For the Matrigel assay, mice were exposed to different doses of
arsenic through drinking water for 1 month. Placenta and Matrigel plug (which was
inserted on gestational day (GD 0.5)) were removed on GD 14. Similar arsenic
concentration was used in CAM assay to observe the effect of vessel development
in hen's eggs. The CAM assay outcome evaluated by Angiosys software showed that
arsenic exposure reduced the total and mean tubule length in all the arsenic
treated groups. The percentage tubule inhibition was declined significantly in
20, 75, and 150 ppm arsenic-treated groups as evaluated by ImageJ software.
Analysis of the CAM outcome by both the image analysis software indicated the
adverse effect of arsenic on the tubules. Further, a significant higher blood
vessel density in 10 ppm and lower vessel density in 20, 75, and 150 ppm arsenic
exposed mice were also observed in Matrigel plug assay. The placental hypertrophy
and dysplasia especially in the labyrinth zone (vasculature) were noted in
placenta of arsenic-treated mice. The study indicated that higher arsenic
exposures inhibited the angiogenesis which was dose-dependent in both CAM and
Matrigel assay and altered structural morphology of placenta. However, no
inhibition of blood vessels was noted at lower, i.e., 10 ppm of arsenic-treated
group.
PMID- 28516353
TI - Physical hazard safety awareness among healthcare workers in Tanta university
hospitals, Egypt.
AB - Hospital workers are exposed to many occupational hazards that may threaten their
health and safety. Physical hazards encountered in hospital working environment
include temperature, illumination, noise, electrical injuries, and radiation. To
assess the awareness of healthcare workers (HCWs) about physical hazards in Tanta
university hospitals, this cross-sectional study included 401 HCWs (physicians,
nurses, technicians, and workers) from seven departments (general surgery,
orthopedics, radiology, ophthalmology, kitchen, incinerator, and laundry). Data
were collected through interview questionnaire to assess six types of physical
hazards (noise, electric hazards, temperature, radiation, fire, and lighting,).
Most of the physicians (63.7%) were aware of the level of noise. All physicians,
nurses, technicians, and majority of workers reported that hearing protective
devices were not available, and all HCWs reported that periodic hearing
examination was not performed. Most of the nurses (75.2%) and workers (68.5%) did
not attended emergency training, and more than two thirds of all HCWs were not
briefed about emergency evacuation. Most HCWs were not given appropriate
radiation safety training before starting work (88% of workers, 73.7% of nurses,
65.7% of physicians, and 68.3% of technicians). The majority of physicians,
nurses, and technicians (70.5, 65.4, and 53.7%) denied regular environmental
monitoring for radiation level inside work place. Health education programs on
health and safety issues regarding physical hazards should be mandatory to all
healthcare workers to improve their awareness and protect them from undue
exposures they may face due to lack of adequate awareness and knowledge. There is
urgent need of expanding the occupational healthcare services in Egypt to cover
all the employees as indicated by the international recommendations and the
Egyptian Constitution, legislation, and community necessity.
PMID- 28516351
TI - Analysis of some metallic elements and metalloids composition and relationships
in parasol mushroom Macrolepiota procera.
AB - The aim of the study was to characterise the multi-elemental composition and
associations between a group of 32 elements and 16 rare earth elements collected
by mycelium from growing substrates and accumulated in fruiting bodies of
Macrolepiota procera from 16 sites from the lowland areas of Poland. The elements
were quantified by inductively coupled plasma quadrupole mass spectrometry using
validated method. The correlation matrix obtained from a possible 48 * 16 data
matrix has been used to examine if any association exits between 48 elements in
mushrooms foraged from 16 sampling localizations by multivariate approach using
principal component (PC) analysis. The model could explain up to 93% variability
by eight factors for which an eigenvalue value was >=1. Absolute values of the
correlation coefficient were above 0.72 (significance at p < 0.05) for 43
elements. From a point of view by consumer, the absolute content of Cd, Hg, Pb in
caps of M. procera collected from background (unpolluted) areas could be
considered elevated while sporadic/occasional ingestion of this mushroom is
considered safe. The multivariate functional analysis revealed on associated
accumulation of many elements in this mushroom. M. procera seem to possess some
features of a bio-indicative species for anthropogenic Pb but also for some
geogenic metals.
PMID- 28516352
TI - Air pollution and respiratory health among diabetic and non-diabetic subjects in
Pune, India-results from the Wellcome Trust Genetic Study.
AB - Diabetics may be more vulnerable to the harmful effects of ambient air pollutants
than healthy individuals. But, the risk factors that lead to susceptibility to
air pollution in diabetics have not yet been identified. We examined the effect
of exposure to ambient PM10 on chronic symptoms and the pulmonary function tests
(PFT) in diabetic and non-diabetic subjects. Also, to investigate possible
determinants of susceptibility, we recruited 400 type 2 diabetic and 465 healthy
subjects who were investigated for chronic respiratory symptoms (CRSs) and then
underwent measurement of forced vital capacity (FVC) and forced expiratory volume
1 (FEV1) according to standard protocol. Percent predicted FEV1 and FVC (FEV1%
and FVC%, respectively) for each subject were calculated. Particulate matter
(PM10) concentrations at residence place of subjects were estimated using AERMOD
dispersion model. The association between PM10 and CRSs was explored using
logistic regression. We also used linear regression models controlling for
potential confounders to study the association between chronic exposure to PM10
and FEV1% and FVC%. Prevalence of current wheezing, allergy symptom, chest
tightness, FEV1/FVC <70%, and physician-diagnosed asthma and COPD was
significantly higher among diabetic subjects than non-diabetics. There was no
significant difference between percent predicted value of PFT among diabetic and
non-diabetic subjects (P < 0.05). We estimated that 1 SD increase in PM10
concentration was associated with a greater risk of having dyspnea by 1.50-fold
(95% CI, 1.12-2.01). Higher exposure to PM10 concentration was also significantly
associated with lower FVC%. The size of effect for 1 SD MUg/m3 (=98.38) increase
in PM10 concentration was 3.71% (95% CI, 0.48-4.99) decrease in FVC%. In
addition, we indicated that strength of these associations was higher in
overweight, smoker, and aged persons. We demonstrated a possible contribution of
air pollution to reduced lung function independent of diabetes status. This study
suggests that decline in exposure may significantly reduce disease manifestation
as dyspnea and impaired lung function. We conduct that higher BMI, smoking, and
older age were associated with higher levels of air pollution effects.
PMID- 28516354
TI - Characterization, partitioning, and potential ecological risk quantification of
trace elements in coal fly ash.
AB - Coal-based thermal power plants are the major source of power generation in
India. Combustion of coal gives rise to by-products such as fly ash (FA) in huge
quantities. The current study focuses on physico-chemical and mineralogical
characterization and risk evaluation of FA, generated from five thermal power
plants (TPPs) of India. The coal, and corresponding FA and bottom ash (BA) were
further analyzed for trace elements in order to observe the enrichment and
partitioning behavior of elements. The environmental risk assessment of trace
elements in FA was performed in accordance with geoaccumulation index (I geo) and
potential ecological risk index (PERI). The results demonstrated that FA was
enriched predominantly in SiO2, Al2O3, and Fe2O3 along with small concentrations
of CaO and MgO. The mineral phases identified in FA were quartz, mullite,
hematite, and magnetite. Elemental characterization indicated that the metals
were more enriched in FA as compared to coal and BA. The concentrations of trace
elements, Cr, Pb, Hg, and As in FA (TPPs), varied from 12.59-24.28, 22.68-43.19,
<0.0001-2.29, and 0.08-3.39 mg/kg, respectively. Maximum enrichment ratio (ER)
was observed for Pb (5.21) in TPP3 FA. Hg in TPP1 showed the highest partition
ratio (PR) value. I geo values for metals were mostly below zero. The PERI values
indicated moderate risk from TPP4 FA and low risk from TPP1, TPP2, TPP3, and TPP5
FA to the environment, according to the threshold values provided.
PMID- 28516355
TI - Valve movement of three species of North American freshwater mussels exposed to
elevated carbon dioxide.
AB - Freshwater mussels are at-risk taxa and may be exposed to high levels of carbon
dioxide (CO2) because of the potential use of CO2 to control the movement of
invasive aquatic fish species. One potential behavioral response to a change in
the partial pressure of CO2 (pCO2) may be altered valve movement. In this study,
three species of mussels were fitted with modified sensors and exposed to two
regimes of pCO2 to define thresholds of impaired valve movement. The first
experiment demonstrated that Pyganodon grandis were much more tolerant to rising
pCO2 relative to Lampsilis siliquoidea (acute closure at ~200,000 MUatm in
comparison to ~80,000 MUatm). The second experiment consisted of monitoring
mussels for 6 days and exposing them to elevated pCO2 (~70,000 MUatm) over a 2
day period. During exposure to high pCO2, Lampsilis cardium were open for nearly
the entire high pCO2 period. Conversely, P. grandis were closed for most of the
period following exposure to high pCO2. For L. siliquoidea, the number of
closures decreased nearly 40-fold during high pCO2. The valve movement responses
observed suggest species differences, and exposure to elevated pCO2 requires a
reactive response.
PMID- 28516356
TI - Morphology, ultrastructure, and element uptake in Calophyllum brasiliense
Cambess. (Calophyllaceae J. Agardh) seedlings under cadmium exposure.
AB - Cadmium (Cd) is a metal known for its genotoxicity and cytotoxicity, much
concerned for its potential environmental and human health impacts. This study
evaluates the toxic effect of Cd in Calophyllum brasiliense plants. The plants
were cultivated for 30 days in full nutrient solution in order to adapt, and for
15 days in nutrient solution without Cd or with 4, 8, 16, and 32 MUmol Cd L-1.
Anatomical analysis of the leaf showed no significant effects of Cd on epidermal
thickness in abaxial and adaxial sides, palisade, and spongy parenchyma.
Contrastingly, changes were noticed in the ultrastructural level in the leaf
mesophyll cells as rupture of the membrane of chloroplasts and disorganization of
the thylakoid membranes, in starch grains and in mitochondria with rupture of the
membrane and invagination of the nuclear membrane. Electron dense materials into
cells of the cortex and vascular bundle were also observed. In the cells of the
root system, the observed ultrastructural changes were disruption of the cell
wall and electron dense material deposition in the cortex cells and vascular
region. Cd accumulated in roots with low translocation into shoot. Cd toxicity
also affected the photosynthetic activity, inducing stomatal closure and
photosynthetic assimilation reduction and the instantaneous carboxylation
efficiency, drastically reducing the leaf transpiration. The nutrient content in
the stem and root was variable, according to Cd increase in nutrient solution.
Based on the experimental evidence, it can be concluded that C. brasiliense has
potential to bioconcentrate high Cd levels in the root system.
PMID- 28516357
TI - Reducing greenhouse gas emissions: a duopoly market pricing competition and
cooperation under the carbon emissions cap.
AB - This article studies the price competition and cooperation in a duopoly that is
subjected to carbon emissions cap. The study assumes that in a departure from the
classical Bertrand game, there is still a market for both firms' goods regardless
of the product price, even though production capacity is limited by carbon
emissions regulation. Through the decentralized decision making of both firms
under perfect information, the results are unstable. The firm with the lower
maximum production capacity under carbon emissions regulation and the firm with
the higher maximum production capacity both seek market price cooperation. By
designing an internal carbon credits trading mechanism, we can ensure that the
production capacity of the firm with the higher maximum production capacity under
carbon emissions regulation reaches price equilibrium. Also, the negotiation
power of the duopoly would affect the price equilibrium.
PMID- 28516358
TI - Mechanistic Modeling of the Pharmacodynamic and Pharmacokinetic Relationship of
Tissue Factor Pathway Inhibitor-Neutralizing Antibody (BAY 1093884) in Cynomolgus
Monkeys.
AB - BAY 1093884 is a fully human monoclonal antibody against the tissue factor
pathway inhibitor (TFPI) in development as prophylaxis in patients with
hemophilia with or without inhibitors. In vitro, BAY 1093884 binds to human,
mouse, and monkey TFPI. The objective of this study was to find a pharmacodynamic
(PD) biomarker after administration of BAY 1093884 to normal monkeys. In monkey
plasma, BAY 1093884 exhibited an IC50 (concentration that inhibits 50%) of 4.65
and 6.19 nM for free TFPI and diluted prothrombin time (dPT), respectively. The
BAY 1093884 pharmacokinetic (PK) profile and its PD effects on dPT and free TFPI
levels were assessed after intravenous and subcutaneous administration of BAY
1093884 (5 and 20 mg/kg) to female cynomolgus monkeys. Free TFPI concentrations
in plasma decreased rapidly and increased to baseline in a dose-dependent manner.
dPT clotting time was shortened and correlated with free TFPI levels and drug
concentration in plasma, demonstrating the relationship between PD activities
(dPT clotting time and free TFPI levels) and drug concentration. BAY 1093884
exhibited nonlinear PK, and a target-mediated drug disposition model was used to
characterize the BAY 1093884 versus TFPI concentration-response relationship. We
concluded that a mechanism-based PK/PD binding model could be useful for
predicting human response to BAY 1093884. For the first-in-human study,
measurement of free TFPI will be included as part of the dose-escalation design.
PMID- 28516360
TI - Gilteritinib, a FLT3/AXL inhibitor, shows antileukemic activity in mouse models
of FLT3 mutated acute myeloid leukemia.
AB - Advances in the understanding of the molecular basis for acute myeloid leukemia
(AML) have generated new potential targets for treatment. Fms-like tyrosine
kinase 3 (FLT3) is one of the most frequently mutated genes in AML and mutations
in this gene are associated with poor overall survival. AXL plays a role in the
activation of FLT3 and has been implicated in the pathogenesis of AML. The
studies reported here evaluated the ability of a novel FLT3/AXL inhibitor,
gilteritinib, to block mutated FLT3 in cellular and animal models of AML. Initial
kinase studies showed that gilteritinib, a type I tyrosine kinase inhibitor, was
highly selective for both FLT3 and AXL while having weak activity against c-KIT.
Gilteritinib demonstrated potent inhibitory activity against the internal tandem
duplication (FLT3-ITD) and FLT3-D835Y point mutations in cellular assays using
MV4-11 and MOLM-13 cells as well as Ba/F3 cells expressing mutated FLT3.
Gilteritinib also inhibited FLT3-F691 mutations, although to a lesser degree, in
these assays. Furthermore, gilteritinib decreased the phosphorylation levels of
FLT3 and its downstream targets in both cellular and animal models. In vivo,
gilteritinib was distributed at high levels in xenografted tumors after oral
administration. The decreased FLT3 activity and high intratumor distribution of
gilteritinib translated to tumor regression and improved survival in xenograft
and intra-bone marrow transplantation models of FLT3-driven AML. No overt
toxicity was seen in mouse models treated with gilteritinib. These results
indicate that gilteritinib may be an important next-generation FLT3 inhibitor for
use in the treatment of FLT3 mutation-positive AML.
PMID- 28516359
TI - Evolution of Choice of Solubility and Dissolution Media After Two Decades of
Biopharmaceutical Classification System.
AB - The introduction of the biopharmaceutics drug classification system
(Biopharmaceutics Classification System (BCS)), in 1995, provided a simple way to
describe the biopharmaceutics behavior of a drug. Solubility and permeability are
among the major parameters, which determine the fraction dose absorbed of a drug
substance and consequently its chances to be bioavailable. The purpose of this
review is to summarize the evolution of the media used for determining solubility
and dissolution and how this can be used in modern drug development. Over the
years, physiologically adapted media and buffers were introduced with the
intention to better predict the in vivo solubility and dissolution of drug
substances. Water, buffer solutions, compendial media, micellar solubilization
media, and biorelevant media are reviewed. At this time point, there is no
universal medium available which can be used to predict every drug substance's
solubility or a drug product's in vivo dissolution behavior. However, there have
been many improvements and additions made to media to optimize their in vivo
predictability; for example, the current phosphate concentrations in buffers seem
to be too high to correlate with the carbonate buffer concentrations in vivo.
Biorelevant media were updated to correlate them better with the composition of
human intestinal fluids. The BCS was introduced into regulatory sciences as a
scientific risk management tool to waive bioequivalence studies under certain
conditions. Today's different guidance documents define the dose-solubility ratio
differently. As shown for amoxicillin, this can cause more confusion than
certainty for globally operating companies. Harmonization of BCS guidelines is
highly desirable.
PMID- 28516362
TI - Evidence for the existence of a communication between the eye and the brain?
PMID- 28516361
TI - Familiarity with Own Population's Appearance Influences Facial Preferences.
AB - Previous studies have found that individuals from rural areas in Malaysia and in
El Salvador prefer heavier women than individuals from urban areas. Several
explanations have been proposed to explain these differences in weight
preferences but no study has explored familiarity as a possible explanation. We
therefore sought to investigate participants' face preferences while also
examining the facial characteristics of the actual participants. Our results
showed that participants from rural areas preferred heavier-looking female faces
than participants from urban areas. We also found that the female faces from the
rural areas were rated as looking heavier than the female faces from the urban
areas. Our findings are consistent with the hypothesis that familiarity may be
contributing to the differences found in face preferences between rural and urban
areas given that people from rural and urban areas are exposed to different
faces.
PMID- 28516363
TI - Posterior reversible encephalopathy syndrome presenting in the anterior
circulation with malignant intracranial hypertension requiring surgical
decompression: a case report and literature review.
AB - Posterior reversible encephalopathy syndrome (PRES) is thought to result from
endothelial dysfunction and breakdown of the blood-brain barrier with subsequent
vasogenic edema. Abrupt hypertension has been identified as one of its risk
factors. We present a rare case of PRES in the anterior circulation with sudden
onset of left hemiparesis and rapid neurological deterioration on the basis of
hypertensive crisis. Due to refractory intracranial hypertension, the patient
required emergent right decompressive craniectomy. Further investigations,
including a biopsy, revealed an atypical form of PRES. This case illustrates the
importance of aggressive medical and early surgical management to prevent
permanent neurological deficits.
PMID- 28516365
TI - Clipping of ruptured intracranial aneurysms in a hybrid room environment-a case
control study.
AB - BACKGROUND: Hybrid room treatment (HRT) provides the surgeon immediate
intraoperative angiography control of aneurysm occlusion and vessel patency.
Since it is relatively resource demanding, in clinical routine HRT is reserved
for elective cases. However, since its introduction in our department in 2008,
several random cases of ruptured intracranial aneurysms (IAs) have been treated
in the HR. This study aims to compare the clinical and radiological outcomes of
these cases with cases treated conventionally using a matched pair analysis.
METHODS: Twenty (20%) consecutive patients with ruptured IA treated by
microsurgical clipping in the HR between 2009 and 2015 were retrospectively
matched with "conventionally" (C) treated patients (overall n = 101). Clinical
and radiological outcome variables were assessed and compared. RESULTS: Despite a
trend in favor of the HR group, no significant difference between both matched
groups (HR vs. C) could be demonstrated regarding the functional outcome
(upper/lower good recovery 16/20 vs. 17/20, p > 0.05), frequency of clipping
related vascular insults on CT scans (0/20 vs. 3/20, p > 0.05), aneurysm remnant
rate on postoperative angiography (1/20 vs. 4/20, p > 0.05) and retreatment rate
(0/20 vs. 1/20, p > 0.05). When cumulating all outcome events by a scoring
system, however, the HR cohort showed a significantly lower occurrence of events
(p < 0.05). In three cases co-treatment by an endovascular approach was performed
in the HR cohort. CONCLUSION: In this relatively small cohort, a matched pair
analysis revealed a discrete but not significant tendency toward a lower
frequency of aneurysm remnants and clipping-related vascular insults in the HR
cohort. However, HR cohort patients benefited from direct endovascular co
treatment in selected cases.
PMID- 28516367
TI - Appropriate or inappropriate ICD shock; what is the post-shock rhythm?
PMID- 28516364
TI - Preserving normal facial nerve function and improving hearing outcome in large
vestibular schwannomas with a combined approach: planned subtotal resection
followed by gamma knife radiosurgery.
AB - OBJECTIVE: To perform planned subtotal resection followed by gamma knife surgery
(GKRS) in a series of patients with large vestibular schwannoma (VS), aiming at
an optimal functional outcome for facial and cochlear nerves. METHODS: Patient
characteristics, surgical and dosimetric features, and outcome were collected
prospectively at the time of treatment and during the follow-up. RESULTS: A
consecutive series of 32 patients was treated between July 2010 and June 2016.
Mean follow-up after surgery was 29 months (median 24, range 4-78). Mean
presurgical tumor volume was 12.5 cm3 (range 1.47-34.9). Postoperative status
showed normal facial nerve function (House-Brackmann I) in all patients. In a
subgroup of 17 patients with serviceable hearing before surgery and in which
cochlear nerve preservation was attempted at surgery, 16 (94.1%) retained
serviceable hearing. Among them, 13 had normal hearing (Gardner-Robertson class
1) before surgery, and 10 (76.9%) retained normal hearing after surgery. Mean
duration between surgery and GKRS was 6.3 months (range 3.8-13.9). Mean tumor
volume at GKRS was 3.5 cm3 (range 0.5-12.8), corresponding to mean residual
volume of 29.4% (range 6-46.7) of the preoperative volume. Mean marginal dose was
12 Gy (range 11-12). Mean follow-up after GKRS was 24 months (range 3-60).
Following GKRS, there were no new neurological deficits, with facial and hearing
functions remaining identical to those after surgery in all patients. Three
patients presented with continuous growth after GKRS, were considered failures,
and benefited from the same combined approach a second time. CONCLUSION: Our data
suggest that large VS management, with planned subtotal resection followed by
GKRS, might yield an excellent clinical outcome, allowing the normal facial nerve
and a high level of cochlear nerve functions to be retained. Our functional
results with this approach in large VS are comparable with those obtained with
GKRS alone in small- and medium-sized VS. Longer term follow-up is necessary to
fully evaluate this approach, especially regarding tumor control.
PMID- 28516366
TI - Patient-Centered Outcomes in Food Allergy.
AB - PURPOSE OF REVIEW: Food allergy prevalence is increasing very rapidly, causing a
significant disease burden. The threat of severe allergic reactions occurring
unexpectedly and in settings that are not equipped to recognize and treat
anaphylaxis is a constant source of worry for individuals and families with food
allergies. Inadequate knowledge and understanding in the community significantly
impairs the overall quality of life of these individuals and families.
Additionally, families face challenges in finding and affording appropriate
allergen-free foods. RECENT FINDINGS: Advancements have been made in
understanding the impact of food allergies on patient-centered outcomes such as
quality of life and economic impact, and attempts have been made to develop tools
to assess patient-centered variables. Innovative national and regional
initiatives are helping to spread awareness of the disease condition and to
create resources, including access to allergen-free foods. While there is a
growing momentum toward recognition of food allergic disorders as a condition
that profoundly impacts activities of daily living, greater effort needs to be
expounded to develop validated tools and interventions that can adequately
address these issues.
PMID- 28516368
TI - Appropriate or inappropriate ICD shock; what is the post-shock rhythm?
PMID- 28516370
TI - Health literacy skills and the benefits of cardiovascular disease prevention.
PMID- 28516369
TI - Management of elderly patients with a non-ST-segment-elevation acute coronary
syndrome.
AB - Elderly patients with an acute coronary syndrome are underrepresented in
randomised controlled trials. Neither the European Society of Cardiology nor the
American Heart Association/American College of Cardiology acute coronary syndrome
guidelines provide specific recommendations for elderly patients. However,
elderly patients are at higher thrombotic and bleeding risk compared with younger
patients leading to difficulties in choosing the optimal treatment. In this
review, we discuss the uncertainties we encounter in treating elderly patients
with non-ST-elevation acute coronary syndrome and suggest treatment options based
on the existing literature.
PMID- 28516371
TI - Perforated emphysematous cholecystitis managed by endoscopic transpapillary
gallbladder drainage.
AB - An 88-year-old woman with dementia was diagnosed as having perforated
emphysematous cholecystitis with localized peritonitis. Because she was at high
risk for surgery, gallbladder drainage was required before surgery. Endoscopic
transpapillary gallbladder drainage instead of percutaneous transhepatic biliary
drainage was performed because bile could leak from the puncture site to free
space around the perforated gallbladder. After the insertion of a nasobiliary
drainage tube, the gallbladder was drained and cleaned with saline solution.
Subsequently, a nasobiliary drainage tube was replaced with a double-pigtail
stent because she was at high risk of dislodging the nasobiliary drainage tube.
Although clinical improvement was observed, she was treated conservatively
without surgery. She was followed up for 6 months without developing
cholecystitis. For perforated cholecystitis without developing panperitonitis,
endoscopic transpapillary gallbladder drainage would be an effective option as a
bridge to surgery for the initial treatment and as an alternative to surgery for
long-term management for a later treatment. This is the first reported case of
perforated emphysematous cholecystitis with localized peritonitis treated with
endoscopic transpapillary gallbladder drainage.
PMID- 28516372
TI - Does thyroid dysfunction increase the risk of breast cancer? A systematic review
and meta-analysis.
AB - PURPOSE: To investigate the relationship between hypothyroidism, hyperthyroidism,
thyroid hormone replacement, and the risk of breast cancer. METHODS: We searched
the PubMed, Cochrane Library, EMbase, Web of Science, and China Biology Medicine
(CBM) databases through June 2016 to identify researches that assessed the
relationship between thyroid dysfunction and the risk of breast cancer together
with the impact of thyroid hormone substitution treatment on incidence of breast
cancer. Quality of evidence was assessed per outcome, using GRADE. RESULTS: A
total of 13 population-based studies including 24,808 participants were
identified as eligible for this meta-analysis. A meta-analysis of 12 researches
illustrated that hypothyroidism was not related to the risk for breast cancer
[odds ratio (OR) = 0.83, 95% confidence interval (CI) 0.64-1.08, P = 0.162]. 10
researches illustrated that hyperthyroidism was also not related to the risk of
breast cancer (OR = 1.03, 95% CI 0.83-1.30, P = 0.767). The impact of therapy was
evaluated in six researches; there was no proof of a relationship between thyroid
hormone substitution treatment and breast cancer with an overall OR of 0.83 (95%
CI 0.57-1.21, P = 0.965). CONCLUSIONS: Our meta-analysis illustrated that thyroid
dysfunction may not be related to increased risk of breast cancer as well as the
thyroid hormone substitution treatment did not reduce the incidence of breast
cancer; while this study has some confounders that might weaken the results of
this meta-analysis, we believe that the findings provide valuable information for
stakeholders concerned with outcomes in patients with thyroid dysfunction.
PMID- 28516373
TI - Class side effects: decreased pressure in the lower oesophageal and the pyloric
sphincters after the administration of dopamine antagonists, neuroleptics, anti
emetics, L-NAME, pentadecapeptide BPC 157 and L-arginine.
AB - The ulcerogenic potential of dopamine antagonists and L-NAME in rats provides
unresolved issues of anti-emetic neuroleptic application in both patients and
experimental studies. Therefore, in a 1-week study, we examined the pressures
within the lower oesophageal and the pyloric sphincters in rats [assessed
manometrically (cm H2O)] after dopamine neuroleptics/prokinetics, L-NAME, L
arginine and stable gastric pentadecapeptide BPC 157 were administered alone
and/or in combination. Medication (/kg) was given once daily intraperitoneally
throughout the 7 days, with the last dose at 24 h before pressure assessment.
Given as individual agents to healthy rats, all dopamine antagonists (central
[haloperidol (6.25 mg, 16 mg, 25 mg), fluphenazine (5 mg), levomepromazine (50
mg), chlorpromazine (10 mg), quetiapine (10 mg), olanzapine (5 mg), clozapine
(100 mg), sulpiride (160 mg), metoclopramide (25 mg)) and peripheral(domperidone
(10 mg)], L-NAME (5 mg) and L-arginine (100 mg) decreased the pressure within
both sphincters. As a common effect, this decreased pressure was rescued, dose
dependently, by BPC 157 (10 ug, 10 ng) (also note that L-arginine and L-NAME
given together antagonized each other's responses). With haloperidol, L-NAME
worsened both the lower oesophageal and the pyloric sphincter pressure, while L
arginine ameliorated lower oesophageal sphincter but not pyloric sphincter
pressure, and antagonized L-NAME effect. With domperidone, L-arginine originally
had no effect, while L-NAME worsened pyloric sphincter pressure. This effect was
opposed by L-arginine. All these effects were further reversed towards a stronger
beneficial effect, close to normal pressure values, by the addition of BPC 157.
In addition, NO level was determined in plasma, sphincters and brain tissue.
Thiobarbituric acid reactive substances (TBARS) were also assessed. Haloperidol
increased NO levels (in both sphincters, the plasma and brain), consistently
producing increased TBARS levels in the plasma, sphincters and brain tissues.
These effects were all counteracted by BPC 157 administration. In conclusion, we
revealed that BPC 157 counteracts the anti-emetic neuroleptic class side effect
of decreased pressure in sphincters and the dopamine/NO-system/BPC 157
relationship.
PMID- 28516375
TI - Effects of Bothrops alternatus venom in zebrafish: a histopathological study.
AB - Zebrafish is an excellent model organism for studying tissue alterations caused
by Bothrops alternatus venom (BAV) and for screening new anti-venom drugs. To
study tissue alterations following exposure to BAV and the roles that
glucocorticoids play in these tissue reactions, zebrafish were randomly divided
into five groups: the free injection control group (FIC), the phosphate-buffered
saline injection control group (PIC), the venom injected group (VI), the group
treated with dexamethasone 1 h before venom injection (D1hBVI) and the group
treated with dexamethasone 1 h after venom injection (D1hAVI). The concentration
of BAV injected was 0.13 mg/mL and each fish received an injection of 20 MUL.
Body weight measurements and histopathological characteristics of the gills,
kidneys, liver, and intestine were determined. Histopathological analyses showed
necrosis, inflammation and weight gain in animals that received BAV. The
histological alteration indices of the gills, liver, kidneys, and intestines were
statistically higher in the animal groups treated with BAV. These alteration
indices were lower in the D1hBVI and D1hAVI groups compared to the group treated
with BAV alone. The D1hBVI group is presented with minor alterations. A
significant difference in the histological alterations index was observed in the
intestinal tissue of the FIC group compared to the PIC group. Cumulatively,
zebrafish may serve as a useful biomarker for alterations induced by BAV.
Interestingly, dexamethasone reduced the damage caused by BAV in the organs
studied, which suggests that zebrafish might be useful for screening new drugs
that can mitigate tissue damage caused by snakebites.
PMID- 28516377
TI - The Influence of Sitagliptin on Treatment-Related Quality of Life in Patients
with Type 2 Diabetes Mellitus Receiving Insulin Treatment: A Prespecified Sub
Analysis.
AB - INTRODUCTION: Treatment-related quality of life (QOL) is an important aspect of
diabetes management. Here, we investigated the influence of sitagliptin, a
dipeptidyl peptidase-4 inhibitor, on treatment-related QOL in patients with type
2 diabetes mellitus treated with insulin. METHODS: This was a prespecified sub
analysis of the Sitagliptin Preventive Study of Intima-Media Thickness Evaluation
(SPIKE). The study population consisted of 71 subjects in the sitagliptin group,
and 62 subjects in the conventional group who were treated with insulin. Patients
of the sitagliptin group were started on sitagliptin in addition to ongoing
insulin therapy. In the conventional group, either increasing the dose of current
insulin therapy or the addition of oral hypoglycemic agents other than dipeptidyl
peptidase-4 inhibitors was allowed to achieve glycemic control. Treatment-related
QOL was evaluated before and 104 weeks after the initiation of the study using
the Diabetes Therapy-Related QOL Questionnaire 7 (DTR-QOL7). RESULTS: Forty-five
out of 71 subjects in the sitagliptin group and 41 out of 62 subjects in the
conventional group filled out the QOL questionnaire at week 104. The DTR-QOL7
score at week 104 was significantly increased from baseline in the sitagliptin
group, while that in the conventional group was not changed. However, the changes
in score did not differ between the two groups. Change in HbA1c was negatively
associated with change in score. CONCLUSIONS: Our data suggest that sitagliptin
added to insulin treatment was comparable to other treatments in terms of its
impact on treatment-related QOL. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov
identifier: UMIN000007396. FUNDING: Mitsubishi Tanabe Pharma Co., Ono
Pharmaceutical Co., and Novo Nordisk.
PMID- 28516374
TI - Role of LPS-elicited signaling in triggering gastric mucosal inflammatory
responses to H. pylori: modulatory effect of ghrelin.
AB - Infection with Helicobacter pylori is a primary culprit in the etiology of
gastric disease, and its cell-wall lipopolysaccharide (LPS) is recognized as a
potent endotoxin responsible for triggering a pattern of the mucosal inflammatory
responses. The engagement by the LPS of gastric mucosal Toll-like receptor 4
(TLR4) leads to initiation of signal transduction events characterized by the
activation of mitogen-activated protein kinase (MAPK) cascade, induction of
phosphoinositide-specific phospholipase C (PLC)/protein kinase C
(PKC)/phosphatidylinositol 3-kinase (PI3K) pathway, and up-regulation in Src/Akt.
These signaling events in turn exert their influence over H. pylori-elicited
excessive generation of NO and PGE2 caused by the disturbances in nitric oxide
synthase and cyclooxygenase isozyme systems, increase in epidermal growth factor
receptor transactivation, and the induction in matrix metalloproteinase-9 (MMP-9)
release. Interestingly, the extent of gastric mucosal inflammatory response to H.
pylori is influenced by a peptide hormone, ghrelin, the action of which relays on
the growth hormone secretagogue receptor type 1a (GHS-R1a)-mediated mobilization
of G-protein dependent transduction pathways. Yet, the signals triggered by TLR-4
activation as well as those arising through GHS-R1a stimulation converge at MAPK
and PLC/PKC/PI3K pathways that form a key integration node for proinflammatory
signals generated by H. pylori LPS as well as for those involved in modulation of
inflammation by ghrelin. Hence, therapeutic targeting these signals' convergence
and integration node could provide a novel and attractive opportunities for
developing more effective treatments of H. pylori-related gastric disease.
PMID- 28516378
TI - HIV Prevalence and Related Risk Factors in Men Who Have Sex with Men in Bamako,
Mali: Findings from a Bio-behavioral Survey Using Respondent-Driven Sampling.
AB - Using respondent driven sampling, we conducted a cross-sectional bio-behavioral
survey among men who have sex with men (MSM) in Bamako, Mali. Eligibility
criteria included age >=18 years and having had sex with another man in the last
6 months. We enrolled 552 MSM, 99.6% were tested for HIV. MSM in Bamako were
young (69.6% <=24 years) and educated (63.7% >=secondary). HIV prevalence among
MSM in Bamako was 13.7; 90.1% of HIV-infected men were unaware of their HIV
status. Almost one-third had never been tested for HIV. Factors associated with
higher odds of HIV included younger age, being receptive with last partner,
condom breaking during anal sex in last 6 months, talking to peer educator about
HIV, and having sexually transmitted infection symptoms in past year. The results
suggest the need for enhanced HIV prevention and treatment services targeted at
MSM in Bamako, with emphasis on repeated HIV testing.
PMID- 28516376
TI - An Update on the Approach to the Imaging of Brain Tumors.
AB - PURPOSE OF REVIEW: Neuroimaging plays a critical role in diagnosis of brain
tumors and in assessment of response to therapy. However, challenges remain,
including accurately and reproducibly assessing response to therapy, defining
endpoints for neuro-oncology trials, providing prognostic information, and
differentiating progressive disease from post-therapeutic changes particularly in
the setting of antiangiogenic and other novel therapies. RECENT FINDINGS: Recent
advances in the imaging of brain tumors include application of advanced MRI
imaging techniques to assess tumor response to therapy and analysis of imaging
features correlating to molecular markers, grade, and prognosis. This review aims
to summarize recent advances in imaging as applied to current diagnostic and
therapeutic neuro-oncologic challenges.
PMID- 28516379
TI - Panobinostat Enhances Growth Suppressive Effects of Progestin on Endometrial
Carcinoma by Increasing Progesterone Receptor and Mitogen-Inducible Gene-6.
AB - Although progestin has been used to treat endometrial hyperplasia and endometrial
carcinoma (EC), its therapeutic efficacy is limited. In order to improve this,
the underlining mechanisms of the effects of progestin need to be elucidated in
more detail. In the present study, we examined the involvement of mitogen
inducible gene-6 (MIG6), a negative regulator of the EGF receptor, in the
progestin-mediated growth suppression of endometrial epithelia. The
immunohistochemical expression of MIG6 was elevated in the early to mid-secretory
phases of normal endometrium and also with endometrial hyperplasia after
medroxyprogesterone acetate (MPA) therapy. The addition of progesterone (P4) to
progesterone receptor (PR)-positive EC cells reduced the viability and induced
MIG6 messenger RNA (mRNA) and protein expression. The silencing of MIG6 using
siRNA eliminated the P4-mediated reduction of EC cell viability, indicating that
MIG6 is an essential downstream component of PR-mediated growth suppression. In
order to enhance PR-driven signals, we examined the effects of histone
deacetylase (HDAC) inhibitors because histone acetylation has been shown to
increase the expression of PR. The addition of three HDAC inhibitors
(panobinostat, LBH589; trichostatin A, TSA; suberoylanilide hydroxamic acid,
SAHA) decreased the viability of EC cells and up-regulated the expression of PR
and MIG6, and these effects were the strongest with LBH589. The addition of
LBH589 and MPA synergistically decreased the viability and increased apoptosis in
EC cells. These results indicate that LBH589 has potential as an enhancer of
progestin therapy via the up-regulation of PR and MIG6.
PMID- 28516380
TI - Polymyalgia rheumatica in a melanoma patient due to nivolumab treatment.
PMID- 28516381
TI - Listening to music during shock wave lithotripsy decreases anxiety, pain, and
dissatisfaction : A randomized controlled study.
AB - BACKGROUND: We analyzed the effects of music on pain, anxiety, and overall
satisfaction in patients undergoing a shock wave lithotripsy (SWL) procedure.
METHODS: A total of 200 patients scheduled to undergo SWL were included in this
study. Group 1 consisted of 95 patients who listened to music during the SWL
session while group 2 included 105 patients who did not listen music during the
procedure. State-Trait Anxiety Inventory (STAI) was used to assess state and
trait anxiety (STAI-S/T). A visual analog scale (VAS) was used at the end of the
session in order to assess pain, willingness to repeat the procedure, and overall
patient satisfaction. Hemodynamic parameters including systolic blood pressure
(SBP), diastolic blood pressure (DBP), and heart rate (HR) were recorded before
and after the session. RESULTS: No statistically significant difference was found
between the two groups in terms of stone characteristics, SWL parameters, pre-SWL
STAI-T/S scores, and pre-SWL hemodynamic parameters. Post-SWL STAI-S scores were
found to be lower in patients who listened to music (p = 0.006). At the end of
the SWL, VAS scores of pain, satisfaction, and willingness to repeat procedure
were significantly different in favor of the music group (p = 0.007, p = 0.001, p
= 0.015, respectively). SBP, DBP, and HR were significantly higher in patients
who did not listen to music (p = 0.002, p = 0.024, p = 0.001, respectively).
CONCLUSION: Music can be an ideal adjunctive treatment modality for patients
undergoing SWL treatment. It has the potential to enhance patient compliance and
treatment satisfaction by reducing the procedure-related anxiety and pain
perception.
PMID- 28516383
TI - Genetic analysis of the Lf1 gene that controls leaflet number in soybean.
AB - KEY MESSAGE: A high-resolution genetic map that was constructed for the Lf1
residing region will provide valuable information for map-based cloning and
genetic improvement efforts in soybean. Changes in leaf architecture as
photosynthesis factories remain a major challenge for the improvement of crop
productivity. Unlike most soybeans, which have compound leaves comprising three
leaflets, the soybean Lf1 mutant has a high frequency of compound leaves with
five leaflets in a partially dominant manner. Here, we generated a fine genetic
map to determine the genetic basis of this multifoliolate leaf trait. A five
leaflet variant Dusam was found in a recently collected landrace cultivar.
Phenotypic data were collected from the F2 population of a cross between the
Dusam and three-leaflet cultivar V94-5152. The mapping results generated using
public markers indicated that the five-leaflet determining gene in Dusam is an
allele of the previously studied Lf1 gene on chromosome 8. A high-resolution map
delimited the genomic region controlling the leaflet number trait to a sequence
length of 49 kb. AP2 domain-containing Glyma.08g281900 annotated in this 49 kb
region appeared to be a strong candidate for the Lf1-encoding gene, as members of
the AP2-type transcription factor family regulate lateral organ development.
Dusam additionally exhibits visually distinct phenotypes for shattering and seed
coat cracking traits. However, the two traits were clearly unlinked to the Lf1
gene in our mapping population. Interestingly, the mapping results suggest that
the Lf1 gene most likely exerts a pleiotropic effect on the number of seeds per
pod. Thus, our results provide a strong foundation towards the cloning of this
compound leaf development gene and marker-assisted selection of the seeds per pod
trait.
PMID- 28516382
TI - Early postoperative growth in non-functioning pituitary adenomas; A tool to
tailor safe follow-up.
AB - PURPOSE: Non-functioning pituitary adenomas are common, and the treatment and
follow-up of these patients represent a multidisciplinary challenge. First line
treatment is transphenoidal surgery, with debulking or total removal of tumour. A
substantial portion of the tumours relapse after surgery, and there is no
consensus of how to follow these patients postoperatively. Our aim was to
characterize the postoperative growth of non-functioning pituitary adenomas and
correlate it to clinical and paraclinical data. METHODS: We retrospectively
registered 52 patients operated for non-functioning pituitary adenomas, with four
or more consecutive MR-investigations not interrupted by secondary treatment.
Adenoma volumes were estimated by the Cavalieri principle with summation of
manually drawn areas multiplied by slice interval. Growth curves were modelled
and tumour volume doubling time was calculated for 39 tumours with regrowth after
surgery. RESULTS: A total of 13 tumours showed exponential growth, 10 linear
growth and 16 logistic growth after surgery. The remaining 13 did not show
regrowth of tumour. Seven of the exponential growing tumours underwent secondary
surgery, compared to one and two of linear and logistic growing tumours (p =
0.03), respectively. Initial tumour volume doubling time was significantly lower
in logistic growing tumours than in exponential growing tumours (p < 0.01). Men
had tumours with lower tumour volume doubling time than women (p = 0.03). None of
the tumours demonstrated signs of accelerated growth. CONCLUSION: Residual
tumours following surgery frequently grow. The logistic growing tumours had the
fastest initial growth in our cohort. We found no indication of accelerated
growth, whereby the tumour volume doubling time might be used to predict a "worst
case" scenario when planning follow-up of these patients.
PMID- 28516384
TI - A mutant in the CsDET2 gene leads to a systemic brassinosteriod deficiency and
super compact phenotype in cucumber (Cucumis sativus L.).
AB - KEY MESSAGE: A novel dwarf cucumber mutant, scp-2, displays a typical BR
biosynthesis-deficient phenotype, which is due to a mutation in CsDET2 for a
steroid 5-alpha-reductase. Brassinosteroids (BRs) are a group of plant hormones
that play important roles in the development of plant architecture, and extreme
dwarfism is a typical outcome of BR-deficiency. Most cucumber (Cucumis sativus
L.) varieties have an indeterminate growth habit, and dwarfism may have its value
in manipulation of plant architecture and improve production in certain
production systems. In this study, we identified a spontaneous dwarf mutant,
super compact-2 (scp-2), that also has dark green, wrinkle leaves. Genetic
analyses indicated that scp-2 was different from two previously reported dwarf
mutants: compact (cp) and super compact-1 (scp-1). Map-based cloning revealed
that the mutant phenotype was due to two single nucleotide polymorphism and a
single-base insertion in the CsDET2 gene that resulted in a missense mutation in
a conserved amino acid and thus a truncated protein lacking the conserved
catalytic domains in the predicted steroid 5alpha-reductase protein. Measurement
of endogenous hormone levels indicated a reduced level of brassinolide (BL, a
bioactive BR) in scp-2, and the mutant phenotype could be partially rescued by
the application of epibrassinolide (EBR). In addition, scp-2 mutant seedlings
exhibited dark-grown de-etiolation, and defects in cell elongation and vascular
development. These data support that scp-2 is a BR biosynthesis-deficient mutant,
and that the CsDET2 gene plays a key role in BR biosynthesis in cucumber. We also
described the systemic BR responses and discussed the specific BR-related
phenotypes in cucumber plants.
PMID- 28516385
TI - Conservative/surgical treatment predictors of maternal hydronephrosis: results of
a single-center retrospective non-randomized non-controlled observational study.
AB - PURPOSE: To determine the parameters that may help the clinicians decide the best
suitable treatment method for the pregnant women with symptomatic hydronephrosis
which will be based on the easily accessible laboratory tests, monitoring methods
and clinical symptoms. METHODS: Digital data and documents of 246 pregnant women
with symptomatic hydronephrosis who were hospitalized in our clinic between the
dates of January 2011 and January 2016 were retrospectively evaluated. All
patients were statistically evaluated in terms of age, symptomatic maximal
anterior-posterior diameter of the renal pelvis (MADP), parity, C-reactive
protein (CRP) level, white blood cell count (WBC), presence of pyuria, growth of
urine culture, fever, serum urine and creatinine levels, visual analog scale
(VAS) score of pre- and post-therapy and threatened preterm labor. RESULTS: The
study includes a total of 211 pregnant women with symptomatic hydronephrosis. In
the second and third trimester groups, the surgical treatment group statistically
provided higher levels of CRP, WBC and VAS. Mean MADP in the second trimester of
the conservative and surgical groups where symptomatic hydronephrosis was on the
right side was 16.67 +/- 4.67 and 28.68 +/- 7.70 mm, respectively. Mean MADP in
the third trimester group of the conservative and surgical groups where
symptomatic hydronephrosis was on the right side was 16.96 +/- 5.96 and 28.85 +/-
7.64 mm, respectively. CONCLUSIONS: In patients with symptomatic pregnancy
hydronephrosis, the likelihood of surgical treatment for CRP levels, WBC counts
and VAS is high.
PMID- 28516387
TI - A diffusion-weighted imaging informed continuum model of the rabbit triceps surae
complex.
AB - The NZ white rabbit is the animal of choice for much experimental work due to its
muscular frame and similar response to human diseases, and is one of the few
mammals that have had their genome sequenced. However, continuum-level
computational models of rabbit muscle detailing fibre architecture are limited in
the literature, especially the triceps surae complex (gastrocnemius, plantaris
and soleus), which has similar biomechanics and translatable findings to the
human. This study presents a geometrical model of the rabbit triceps surae
informed with diffusion-weighted imaging (DWI)-based fibres. Passive rabbit
specific material properties are estimated using known muscle deformation
inferred from magnetic resonance imaging data and dorsiflexion force measured
with a custom-built rabbit rig and transducer. Muscle shape prediction is
evaluated against a second rabbit. This study revealed that the triceps surae
steady-state force post-rigor is close to post-mortem for small deformations but
increases by a fixed ratio as the deformation increases and can be used to
evaluate the passive behaviour of muscle. DWI fibre orientation significantly
influences shape and mechanics during simulated computational muscle contraction.
The presented triceps surae force and material properties may be used to inform
the constitutive behaviour of continuum rabbit muscle models used to investigate
pathology and musculotendon treatments that may be translated to the human
condition.
PMID- 28516386
TI - Intergenerational Transmission of Depressive Symptoms: The Role of Parental
Negative Perceptions and Behaviors.
AB - This study examined parental proximal processes involving in the
intergenerational transmission of depressive symptoms from parents to their
children. Extant literature has predominantly focused on maternal depressive
symptoms. Yet, the mechanisms that may underlie the transmission of paternal
depressive symptoms is less often studied. Participants were Chinese parents of
first-graders (N = 2282). Results of structural equation modeling suggested that
maternal and paternal depressive symptoms may be transmitted to their children
through differential processes. Depressive symptoms in mothers, but not in
fathers, were associated with their negatively-biased perceptions and
dysfunctional parenting practices, which then predicted depressive symptoms in
children. Moreover, mothers' depressive symptoms were associated with children's
depressive symptoms regardless of child gender, whereas fathers' depressive
symptoms were associated with boys', but not girls', depressive symptoms.
Findings expand the understandings on parental processes in the intergenerational
transmission of depressive symptoms in families, the role of paternal depressive
symptoms in promoting children's depressive symptoms, and who may be at
particular risks for psychopathology in the face of parental depressive symptoms.
PMID- 28516388
TI - Effects of Different Selenium Sources on Growth Performance, Antioxidant Capacity
and Meat Quality of Local Chinese Subei Chickens.
AB - Despite increasing evidence indicating the essential involvement of selenium (Se)
on growth performance, antioxidant capacity, and meat quality of commercial
broilers, the effects of different Se sources on local Chinese Subei chickens is
unclear. A total of 360 50-day-old male chickens were individually weighed and
randomly allocated to four treatment groups. Chickens in each of the four groups
were fed diets supplemented with 0.3 mg Se/kg as sodium Se (SS), Se-enriched
yeast (SY), selenomethionine (Met-Se), or nano red element Se (Nano-Se) for 40
days. At the end of the experiment, one bird of approximately average weight from
each cage was selected and slaughtered, and blood and breast muscles samples were
collected. The results showed that there was no significant difference in feed
intake, body weight gain, or feed to gain ratio among treatments (P > 0.05).
Dietary SY, Met-Se, and Nano-Se supplementation increased the activity of
glutathione peroxidase in serum and breast muscles and decreased the
concentration of malondialdehyde in serum and carbonyl in breast muscles compared
with the SS group (P < 0.05). Moreover, SY, Met-Se, and Nano-Se supplementation
increased pH45min, total protein solubility, and myofibrillar protein solubility,
as well as decreased the shear force value compared with the SS group (P < 0.05).
In addition, birds in the SY and Met-Se groups exhibited lower cooking loss
compared with the SS group (P < 0.05). In conclusion, organic Se and Nano-Se
supplementation resulted in an improvement of antioxidant capacity and meat
quality in local Chinese Subei chickens relative to inorganic Se.
PMID- 28516389
TI - Microenvironmental Scenario of the Bone Marrow of Inorganic Arsenic-Exposed
Experimental Mice.
AB - Exposure to arsenic on a regular basis, mainly through drinking water,
agricultural pesticide, and sometimes therapeutic dose, results in various
diseases of different tissues including the bone marrow hematopoietic system.
Hematopoiesis is a dynamic process by which bone marrow (BM) hematopoietic
stem/progenitor cells (HSPCs) generate a relatively constant pool of functionally
mature blood cells by the support of microenvironmental components. The present
study has been aimed to understand stem cell microenvironmental status during
arsenic toxicity and the consequent reflection of dysregulation involving the
hematopoietic machinery in experimental mice. Swiss albino mice were
experimentally exposed to 10 MUg arsenic trioxide/g body weight through oral
gavage and 5 MUg arsenic trioxide/g body weight intraperitoneally for a period of
30 days. Altered hemogram values in peripheral blood reflected the impaired
hematopoiesis which was further validated by the reduced BM cellularity along
with the deviated BM cell morphology as observed by scanning electron microscopy
post arsenic exposure. The stromal cells were unable to establish a healthy
matrix and the sustainability of hematopoietic progenitors was drastically
affected in arsenic-exposed mouse groups, as observed in in vitro explant
culture. The inability of stromal cells to establish supportive matrix was also
explained by the decreased adherent colony formation in treated animals.
Furthermore, the flow cytometric characterization of CXCR4+ and Sca-1+ CD44+
receptor expressions confirmed the dysregulation in the hematopoietic
microenvironment. Thus, considering the importance of microenvironment in the
maintenance of HSPC, it can be concluded that arsenic toxicity causes
microenvironmental damage, leading to niche derangement and impaired
hematopoiesis.
PMID- 28516390
TI - The Identity of "Chromium Malate".
AB - Recently, several studies on the effects of a compound named "chromium malate,"
with the proposed formula "Cr2malate3.xH2O" where x = 3.5 or 5, on the health of
healthy and diabetic rats have appeared. However, the compound is poorly
characterized, and knowing the identity of this material could be important in
the interpretation of the previous and of future studies on the effects of this
compound in animals. Consequently, the synthesis, characterization, and identity
of this material were explored. A combination of spectroscopic, magnetic, and
elemental analyses and mass spectral studies reveal that the compound is probably
a polymer, not a discrete molecule, and does not have the composition previously
reported. The repeating unit of the polymer possesses an antiferromagnetically
coupled trinuclear Cr(III) core. The current study suggests that previous reports
on chromium malate and its effects in animals must be viewed with caution.
PMID- 28516391
TI - Denial of a sleep deprivation message: situational and dispositional influences
on message rejection.
AB - Two studies investigated situational and dispositional influences on rejection of
a sleep deprivation warning message for young adults. The hassle of protection
(Study 1) and the self-relevance of the problem (Study 2) were manipulated; the
disposition to use denial (threat orientation) for warning messages was measured.
In both studies, it was found that both dispositional denial and the situational
manipulation (more protection-hassle or self-relevance) showed at least one
denial effect by reducing perceived susceptibility, perceived severity, or
credibility. Indirect (mediational) effects were tested with the bootstrap
method. In Study 1, judgments of credibility and severity mediated the effects of
the hassle manipulation and denial orientation on message outcomes. In Study 2,
credibility mediated the effects of the self-relevance manipulation and denial
orientation on message outcomes of intentions to change and priority given to
sleep. These studies show that both situational and dispositional sources of
denial work in similar ways by lowering key message judgments and that the lower
judgments lead to less priority given to a health risk and lower intentions to
protect oneself.
PMID- 28516392
TI - Cavernous sinus thrombosis in a patient with nephrotic syndrome.
PMID- 28516395
TI - Thoracoscopic partial resection without using a stapler. (complete
republication).
AB - Thoracoscopic partial pulmonary resection for small peripheral nodules without
using a stapler has been introduced to our hospital. After partial resection was
performed with electrocautery, two different methods of surface sealing were
used: a coagulation method (C method) with Soft Coagulation alone, and a
coagulation-suturing method (CS method) with Soft Coagulation combined with
continuous suturing. The clinical outcomes of the two methods were
retrospectively compared in this study. The C method was used in 19 lesions of 18
cases, and the CS method was used in 20 lesions of 19 cases. Primary lung cancer
was the most frequent diagnosis (22 lesions of 21 cases). There were no
differences between the two groups in the size and depth of the lesions.
Operative time was longer with the CS method than with the C method.
Postoperative air leakage was a complication in 4 cases with the C method, and
one of them required re-do surgery, whereas only one case with the CS method had
temporary air leakage. Postoperative computed tomography showed cavitation in 3 C
method cases and 5 CS method cases, all without related symptoms. There were no
local recurrences at resected sites. In conclusion, the C method was technically
easy to perform, but air leakage may be prolonged after surgery. The CS method
may have the advantage of causing less air leakage than the C method, but
mastering the technique is important to shorten operative time.
PMID- 28516393
TI - Plasma MMP2/TIMP4 Ratio at Follow-up Assessment Predicts Disease Progression of
Idiopathic Pulmonary Arterial Hypertension.
AB - PURPOSE: Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs)
are of particular interest in the remodeling processes of pulmonary hypertension.
The aim of this study was to investigate MMP/TIMP ratios of selected biomarkers
(MMP2, MMP9, TIMP1, TIMP4) at follow-up examination (V2) and their prognostic
value in patients with idiopathic pulmonary arterial hypertension (iPAH).
METHODS: Blood samples were taken from iPAH patients during right heart
catheterization at diagnosis (V1, from 2003 to 2012) and first follow-up
examination (V2). MMP2, MMP9, TIMP1, and TIMP4 plasma levels at V2 were
determined by ELISA. Coincident with sample collection hemodynamic, laboratory,
and clinical parameters were acquired. Additionally, death and clinical worsening
(CW) events were listed until July 2015. RESULTS: MMP2/TIMP1 and MMP9/TIMP1 did
not correlate with hemodynamic and clinical parameters. MMP2/TIMP4 showed a good
correlation with mean pulmonary arterial pressure (mPAP), pulmonary vascular
resistance, estimated glomerular filtration rate (eGFR), and tricuspid annular
plain systolic excursion (TAPSE). MMP9/TIMP4 shows good correlation with mPAP and
eGFR. MMP2/TIMP4 showed significant results in the receiver operating
characteristics analysis predicting death (AUC = 0.922; p = 0.005) and CW event
(AUC = 0.818; p = 0.026). Patients above the cut-off values had a significantly
higher probability to die or experience CW, respectively, estimated by log-rank
test (p = 0.010 for death; p = 0.032 for CW). CONCLUSIONS: MMP2/TIMP4 ratio was
detected as a marker of disease severity and right ventricular function as well
as a predictor for survival and time to clinical worsening and therefore might
help for guidance of disease progression in iPAH patients at V2.
PMID- 28516396
TI - Body Sanctification and Sleep in Adolescents with Cystic Fibrosis: A Pilot Study.
AB - Imbuing one's body with divine significance is associated with health-protective
behaviors. The purpose of this study was to determine whether adolescents with a
life-shortening, chronic disease (cystic fibrosis) who sanctified their bodies
also received adequate sleep. Data from Daily Phone Diaries and questionnaire
replies from 45 adolescents with cystic fibrosis (ages 11-19 years) were
analyzed. A significant relationship between body sanctification and sleep was
found, with between-gender differences. Body sanctification is an understudied
construct which is associated with healthy behaviors.
PMID- 28516397
TI - Perspective of Islamic Self: Rethinking Ibn al-Qayyim's Three-Heart Model from
the Scope of Dynamical Social Psychology.
AB - The present article proposes the perspective of Islamic self (PIS), which is
guided by three core principles. First, the Islamic self is shaped by the God's
predicament: The life test. Second, the structure of the self and its spiritual
virtues represent means to succeed the life test. Third, the complex dynamics of
the self can be mathematically formalized into a parsimonious framework.
Specifically, the PIS considers the self as a dynamical system characterized by
the emergence of self-organized stable and unstable patterns taking the form of
positive ("illuminating heart") or negative ("darkened heart") dynamics.
PMID- 28516394
TI - Linguistic asymmetry, egocentric anchoring, and sensory modality as factors for
the observed association between time and space perception.
AB - Temporal and spatial representations have been consistently shown to be
inextricably intertwined. However, the exact nature of time-space mapping remains
unknown. On the one hand, the conceptual metaphor theory postulates unilateral,
asymmetric mapping of time onto space, that is, time is perceived in spatial
terms but the perception of space is relatively independent of time. On the other
hand, a theory of magnitude assumes bilateral and symmetric interactions between
temporal and spatial perceptions. In the present paper, we argue that the
concepts of linguistic asymmetry, egocentric anchoring, and sensory modality
provide potential explanations for why evidences favoring both asymmetry and
symmetry have been obtained. We first examine the asymmetry model and suggest
that language plays a critical role in it. Next, we discuss the symmetry model in
relation to egocentric anchoring and sensory modality. We conclude that since
these three factors may jointly account for some conflicting past results
regarding the strength and directionality of time-space mapping, they should be
taken into serious consideration in future test designs.
PMID- 28516399
TI - Hangeshashinto (TJ-14) prevents radiation-induced mucositis by suppressing
cyclooxygenase-2 expression and chemotaxis of inflammatory cells.
AB - PURPOSE: Radiation-induced oral mucositis is the most common side effect of
radiotherapy in head and neck cancer; however, effective modalities for its
prevention have not been established. In this study, we evaluated the
effectiveness of Hangeshashinto (TJ-14), a Japanese herbal medicine, for
preventing radiation-induced mucositis and elucidated its effect on inflammatory
responses, including inflammatory cell chemotaxis and cyclooxygenase-2 (COX2)
expression, in an animal model. METHODS: Syrian hamsters, 8-9 weeks old, were
enrolled in this study. Animals were irradiated with a single 40 Gy dose to the
buccal mucosa. Hamsters freely received a treatment diet mixed with 2% TJ-14 or a
normal diet daily. The therapeutic effect was determined based on the visual
mucositis score, body weight, and histological examination of infiltrated
neutrophils and COX2 expression. RESULTS: TJ-14 significantly reduced the
severity of mucositis. The percentage with severe mucositis (score >=3) was 100%
in the untreated group and 16.7% in the TJ-14 group (P < 0.05). There was no
difference in body weight change between the groups; however, weight gain in the
untreated group tended to be suppressed compared to that in the TJ-14 group
during the peak period of mucositis. In addition, TJ-14 inhibited the
infiltration of neutrophils and COX2 expression in irradiated mucosa (P < 0.05).
CONCLUSIONS: TJ-14 reduced the severity of mucositis in an animal model by
suppressing the inflammatory response. Because TJ-14 is inexpensive and its
safety is established, it is a promising candidate for the standard treatment of
radiation-induced mucositis in cancer patients.
PMID- 28516398
TI - Gynecological brachytherapy for postoperative endometrial cancer: dosimetric
analysis (Ir-192 vs Co-60).
AB - INTRODUCTION: Endovaginal brachytherapy treatment dosimetry differences were
studied using Ir-192 or Co-60 sources for postoperative endometrial cancer.
MATERIALS AND METHODS: A prospective descriptive study was conducted. Thirty-six
dosimetry plans of different patients were studied (15 by Ir-192 and 21 by Co
60). Variables studied included D2cc Rectum, D2cc Bladder, D2cc Sigmoid, dose
percentage at point 0 (applicator surface on the top of the cylinder) and dose
percentage at point 1 (5 mm deep on the top of the cylinder). A comparative
analysis was performed of the values obtained from each variable between Ir-192
and Co-60 treatments. We compared average of each variables between Iridium and
Cobalt by T Student for independent samples (SPSS 22). RESULTS: There were no
significant differences on using Ir-192 or Co-60 by variables, except for dose
percentage at point 1 in which we detected significant differences (Table 1).
Table 1 The results Variables Sources Iridium 192 Cobalt 60 D2cc Rectum (mean
dose) [rank] 6.01 Gy [3.99-7.90] 5.28 Gy [3.87-6,34] D2cc Bladder (mean dose)
[rank] 5.82 Gy [4.20-8.38] 5.05 Gy [2.23-6.95] D2cc Sigmoid (mean dose) [rank]
4.43 Gy [1.66-6.67] 2.33 Gy [0.60-4.28] Dose percentage at point 0a (mean) [rank]
210.74% [120.90-234.90] 204.75% [177.10-223] Dose percentage at point 1b (mean)
[rank] 93.49% [87.30-100.60] 100.11% [96.70-102] aPoint 0: point to the
applicator surface bPoint 1: point to 5 mm applicator surface DISCUSSION:
Brachytherapy treatment dosimetry plans are similar using Ir-192 or Co-60, except
dose percentage at point 1. In the scientific literature, some differences exist
and there are some advantages in using cobalt.
PMID- 28516401
TI - Endovascular Crossing of Chronic Total Occlusions Using an Impulse: An
Explorative Design Study.
AB - In this study we investigated whether exerting an impulse on a Chronic Total
Occlusion (CTO) improves the success rate of CTO crossing as compared to the
currently used method of statically pushing the guidewire against the CTO. A
prototype (O2 mm) was developed that generates translational momentum using a
spring-loaded indenter and converts it to an impulse during impact. Mechanical
performance was evaluated by measuring the peak force and momentum for different
spring compressions and strike distances in air and blood-mimicking fluid.
Puncture performance, in terms of number of punctures, number of strikes to
puncture, and energy transfer from the indenter to the CTO, was assessed for six
tip shapes (stamp, wedge, spherical, pointed, hollow spherical, and ringed) on
three CTO models with different weight percentages of gelatin and calcium. As a
control, a O0.4 mm rigid rod was tested. A maximum indenter momentum of 1.3 mNs
(velocity of 3.4 m/s), a peak force of 19.2 N (vs. 1.5 N reported in literature
and 2.7 N for the control), and CTO displacement of 1.4 mm (vs. 2.7 mm for the
control) were measured. The spherical and ringed tips were most effective, with
on average 2.3 strikes to puncture the most calcified CTO model. The prototype
generated sufficient peak forces to puncture highly calcified CTO models, which
are considered most difficult to cross during PCI. Furthermore, CTO displacement
was minimized, resulting in a more effective procedure. In future, a smaller,
faster, and flexible clinical prototype will be developed.
PMID- 28516400
TI - Systematic Investigation of the Role of Surfactant Composition and Choice of oil:
Design of a Nanoemulsion-Based Adjuvant Inducing Concomitant Humoral and CD4+ T
Cell Responses.
AB - PURPOSE: Induction of cell-mediated immune (CMI) responses is crucial for vaccine
mediated protection against difficult vaccine targets, e.g., Chlamydia
trachomatis (Ct). Adjuvants are included in subunit vaccines to potentiate immune
responses, but many marketed adjuvants stimulate predominantly humoral immune
responses. Therefore, there is an unmet medical need for new adjuvants, which
potentiate humoral and CMI responses. The purpose was to design an oil-in-water
nanoemulsion adjuvant containing a synthetic CMI-inducing mycobacterial
monomycoloyl glycerol (MMG) analogue to concomitantly induce humoral and CMI
responses. METHODS: The influence of emulsion composition was analyzed using a
systematic approach. Three factors were varied: i) saturation of the oil phase,
ii) type and saturation of the applied surfactant mixture, and iii) surfactant
mixture net charge. RESULTS: The emulsions were colloidally stable with a droplet
diameter of 150-250 nm, and the zeta-potential correlated closely with the net
charge of the surfactant mixture. Only cationic emulsions containing the
unsaturated surfactant mixture induced concomitant humoral and CMI responses upon
immunization of mice with a Ct antigen, and the responses were enhanced when
squalene was applied as the oil phase. In contrast, emulsions with neutral and
net negative zeta-potentials did not induce CMI responses. The saturation degree
of the oil phase did not influence the adjuvanticity. CONCLUSION: Cationic, MMG
analogue-containing nanoemulsions are potential adjuvants for vaccines against
pathogens for which both humoral and CMI responses are needed.
PMID- 28516402
TI - Effects of calcineurin inhibitors on sodium excretion in recipients of allogeneic
hematopoietic stem cell transplantation.
AB - Calcineurin inhibitors (CIs) such as cyclosporine A (CSA) and tacrolimus often
cause renal dysfunction, resulting in increased serum creatinine, hyperkalemia,
and hyperuricemia. However, the effects of CIs on sodium excretion have not been
fully elucidated. We retrospectively evaluated the effects of CI administration
on sodium excretion in recipients of allogeneic hematopoietic stem cell
transplantation (HSCT). Fifty consecutive recipients each of allogeneic HSCT
receiving either CSA or tacrolimus (100 patients in total) with available data
for weekly fractional excretion of sodium (FENa) for a 4-week period after
transplantation were enrolled in this retrospective analysis. No significant
differences in patient characteristics were observed between CSA and tacrolimus
groups except for the type of donor. FENa was significantly higher at the 3rd
(1.25 +/- 0.80) and 4th weeks (1.53 +/- 1.06) after transplantation as compared
with that at the 1st week (0.93 +/- 0.51; P < 0.01, P < 0.001, respectively) in
the tacrolimus group, but not at any time point in the CSA group. In addition,
FENa was significantly higher in the tacrolimus group than the CSA group at the
4th week (1.53 +/- 1.06 vs. 1.13 +/- 0.80; P < 0.05). These results suggest that
tacrolimus increases sodium excretion after allogeneic HSCT, and that this effect
is minimal with CSA.
PMID- 28516404
TI - Screening for Diabetic Eye Disease among Samoan Adults: A Pilot Study.
AB - INTRODUCTION: The purpose of this study was to determine the prevalence of
diabetic retinopathy in Samoa by piloting a retinal photography screening
programme. METHODS: We performed a cross-sectional study of patients with
diabetes who presented to the Tupua Tamasese Meaole eye clinic in Apia, Samoa,
between May 2011 and September 2011. Study approval was granted by the National
Health Service Board of Samoa, the Monash University Human Research Ethics
Committee, and the study adhered to the Tenets of the Declaration of Helsinki.
Following informed consent, data collection included patient demographics [age,
area of residence (rural or urban)], type of diabetes, length of time since
diagnosis, most recent random blood sugar and blood pressure levels. The subjects
had three 45-degree retinal photographs taken in each eye with the Canon CR6-45NM
camera. All gradable photographs were assessed for the presence of diabetic
retinopathy or macular oedema using the International Clinical Diabetic
Retinopathy Severity Scale and the International Clinical Diabetic Macular Oedema
Severity scale, respectively. RESULTS: Two hundred and fourteen eyes from 107
subjects were examined during the study period, all of whom had type 2 diabetes
mellitus. Diabetic retinopathy was present in 53.3% (114/214) of eyes, with 14.5%
having proliferative retinopathy and 7.5% with severe non-proliferative
retinopathy. Also, 25.2% (54/214) had some evidence of macular oedema with 11.7%
(25/214) requiring treatment. A statistically significant relationship existed
between the length of time since diagnosis and the severity of both retinopathy
(p < 0.001) and macular oedema (p = 0.031). Blood pressure more than 150/85 mmHg
was associated with higher levels of diabetic retinopathy (p = 0.03) and macular
oedema (p = 0.02). CONCLUSION: A comprehensive diabetic retinopathy screening
programme is much needed in Samoa given the high prevalence of diabetic eye
disease.
PMID- 28516403
TI - Long-term clinical outcome of spinal Langerhans cell histiocytosis in children.
AB - Spinal involvement of Langerhans cell histiocytosis (LCH) affects morbidity, but
outcomes are not well understood. We analyzed long-term outcomes following
uniform treatment at a single institution. Clinical characteristics and outcomes
of spinal LCH patients were retrospectively analyzed. Height ratios were
calculated using the anterior height of the involved vertebral body on magnetic
resonance imaging (MRI) and the expected normal vertebral height. Twenty-two
(22.4%) of 98 patients diagnosed with LCH had spinal involvement. The median age
at diagnosis was 4.1 (range 0.6-12.3) years. Thirty-one spinal lesions were
identified in 22 patients; the thoracic spine (n = 17) was most commonly
affected. Eight lesions with minimal collapse, which appeared normal on plain
radiography, were detected with MRI. All patients received vinblastine-based
chemotherapy. Fourteen (70%) of 20 evaluable vertebral body collapses, including
eight severe lesions, showed improvement in vertebral body height at a median
follow-up of 6.0 (range 2.8-12.0) years. All traceable patients were alive
without disease. Long-term follow-up of vertebral body collapse revealed
vertebral height improvement in approximately 70% of spinal LCH patients, even in
severe cases. MRI at diagnosis detected spinal lesions earlier with higher
sensitivity than plain radiography.
PMID- 28516407
TI - Components of sustainability considerations in management of petrochemical
industries.
AB - Sustainability comprises three pillars of social, environmental, and economic
aspects. Petrochemical industry has a great inter-related complex impact on
social and economic development of societies and adverse impact on almost all
environmental aspects and resource depletion in many countries, which make
sustainability a crucial issue for petrochemical industries. This study was
conducted to propose components of sustainability considerations in management of
petrochemical industries.A combination of exploratory study-to prepare a
preliminary list of components of sustainable business in petrochemical
industries based on review of literature and Delphi-to obtain experts' view on
this preliminary list and provide a detailed list of components and sub
components that should be addressed to bring sustainability to petrochemical
industries, were used.Two sets of components were provided. First general
components, which include stakeholders (staffs, society, and environment) with
four sub-components, financial resources with 11 sub-components, improvement of
design and processes with nine sub-components, policy and strategy of cleaner
production with seven sub-components and leadership with seven sub-components.
The second operational components included raw material supply and preparation
with five, synthesis with ten, product separation and refinement with nine,
product handling and storage with five, emission abatement with eight, and
improvement of technology and equipment with 16 sub-components.
PMID- 28516406
TI - Degradation and adsorption of tralkoxydim in Chinese soils and water-sediment
environments.
AB - Tralkoxydim is a cyclohexanedione herbicide primarily used for gramineous weed
control in China. In this paper, we present results of a tralkoxydim laboratory
environmental fate study characterizing its degradation, adsorption, and mobility
behavior in three different soils and two water-sediment systems (river and lake)
in China. Degradation half-life of tralkoxydim in soil under aerobic conditions
was 5.1, 7.7, and 7.9 days in Jiangxi red soil, Taihu paddy soil, and Northeast
China black soil, respectively. Under anaerobic and flooding conditions, half
life values were 6.2, 15.1, and 19.8 days for the same three soils, respectively.
Soil pH was the major factor effecting tralkoxydim degradation. In the aerobic
water-sediment experiments, tralkoxydim degraded faster in the river system
(total system half-life 43.3 days) than the lake system (total system half-life
99.0 days). Correspondingly, its anaerobic degradation half-life values were 46.2
and 53.3 days for the river and lake systems, respectively. Tralkoxydim
adsorption in the three soils was found to follow the empirical Freundlich
isotherm. The adsorption coefficient (K d ) was 8.60, 1.00, and 1.57 for Jiangxi
red soil, Taihu paddy soil, and Northeast China black soil, respectively. Soil pH
was the major factor effecting tralkoxydim adsorption. Adsorption free energy
change was less than 40 kJ mol-1 in all three soils, indicating a physical
mechanism in the process. Thin-layer chromatography (TLC) tests showed that
relative to the solvent transport to 11.5 cm, the travel distance of tralkoxydim
was 8-10 cm in the three soils, corresponding Rf values at 0.05, 0.35, and 0.75
for Jiangxi red soil, Taihu paddy soil, and Northeast China black soil,
respectively. Results of this work suggest that under alkaline conditions,
tralkoxydim adsorption becomes smaller; thus, assessments on its mobility and
potential groundwater impact should focus on these soil types.
PMID- 28516405
TI - Characterization of dissolved organic matter in an urbanized estuary located in
Northeastern Brazil.
AB - The Sal River estuary, which is located in the state of Sergipe, Northeastern
Brazil, stands out as an urban estuary, anthropogenically impacted by untreated
and treated wastewater discharge. Synchronous fluorescence spectroscopy and
measurement of dissolved organic carbon (DOC) were used for characterization of
dissolved organic matter (DOM) in the estuarine water. Dissolved organic carbon
concentrations ranged from 7.5 to 19.0 mg L-1 and, in general, the highest values
were recorded during dry season. For both seasons (dry and rainy), DOC presented
an inverse linear relationship with salinity, which indicates a conservative
dilution of organic matter coming into the estuary. During rainy season,
anthropogenic organic constituents and humic substances from land-based sources
predominated in DOM composition, carried by river flow. Whereas during the dry
season, it has been observed a significant increase of products generated by
microbial degradation of anthropogenic organic matter. The relationships between
fluorescence intensity and salinity suggest a conservative behavior during rainy
season and a non-conservative behavior during dry season, with addition of
fluorescent organic matter into the intermediate zone of the estuary.
Photodegradation by action of sunlight caused a decrease in fluorescence
intensity of humic and tryptophan-like constituents and the release of
photoproducts, resulting in an increase in fluorescence intensity of protein-like
constituents.
PMID- 28516408
TI - The Poisoning Severity Score: If It Did Not Exist, We Would Have To Invent It.
PMID- 28516410
TI - Silymarin-Loaded Eudragit Nanoparticles: Formulation, Characterization, and
Hepatoprotective and Toxicity Evaluation.
AB - The objectives of this study were to formulate, characterize silymarin-loaded
Eudragit nanoparticles (SNPs) and evaluate their hepatoprotective and cytotoxic
effects after oral administration. SNPs were prepared by nanoprecipitation
technique and were evaluated for particle size, entrapment efficiency, TEM, solid
state characterization, and in vitro drug release. The hepatoprotective activity
was evaluated after oral administration of selected SNPs in carbon tetrachloride
intoxicated rats. Potential in vivo acute cytotoxicity study was also assessed.
The selected SNPs contained 50 mg silymarin and 50 mg Eudragit polymers (1:1 w/w
Eudragit RS 100 & Eudragit LS 100). Morphology of the selected SNPs (particle
size of 84.70 nm and entrapment efficiency of 83.45% with 100% drug release after
12 h) revealed spherical and uniformly distributed nanoparticles. DSC and FT-IR
studies suggested the presence of silymarin in an amorphous state and absence of
chemical interaction. The hepatoprotective evaluation of the selected SNPs in
CCl4-intoxicated rats revealed significant improvement in the activities of
different biochemical parameters (P <= 0.01) compared to the marketed product.
The histopathological studies suggested that the selected SNPs produced better
hepatoprotective effect in CCl4-intoxicated rats compared with the commercially
marketed product. Toxicity study revealed no evident toxic effect for blank or
silymarin-loaded nanoparticles at the dose level of 50 mg/kg body weight. The
obtained results suggested that the selected SNPs were safe and potentially
offered enhancement in the pharmacological hepatoprotective properties of
silymarin.
PMID- 28516409
TI - Survival After Severe Rhabdomyolysis Following Monensin Ingestion.
AB - INTRODUCTION: Monensin is a veterinary antibiotic with a narrow therapeutic
window that has led to lethal intoxication in many animal species. Only two prior
cases of human toxicity have been reported, both fatal. We present the first case
of survival from severe toxicity following monensin ingestion. CASE: A 58-year
old man presented with 8 days of vomiting and abdominal pain. Due to delusions of
central nervous system toxoplasmosis, he ingested 300 mg of monensin. His
laboratory studies revealed severe rhabdomyolysis without renal dysfunction.
Total creatine kinase (CK) peaked above 100,000 U/L. His CK decreased to 5192 U/L
after 15 days of aggressive hydration and sodium bicarbonate therapy. His
ejection fraction on echocardiogram decreased from 69 to 56%. DISCUSSION: Reports
on acute clinical effects after human exposure to monensin are limited. Ingestion
is known to cause skeletal and cardiac muscle rhabdomyolysis and necrosis. Animal
studies demonstrate that monensin's toxicity is due to increases in intracellular
sodium concentrations and Ca2+ release. To date, no effective antidotal treatment
has been described. CONCLUSIONS: Monensin is a veterinary medication not approved
for human use by the US Food and Drug Administration. Though poorly studied in
humans, this case demonstrates the severe harm that may occur following
ingestion.
PMID- 28516411
TI - Preparation of Essential Oil-Based Microemulsions for Improving the Solubility,
pH Stability, Photostability, and Skin Permeation of Quercetin.
AB - Quercetin can bring many benefits to skin based on its various bioactivities.
However, the therapeutic effect of quercetin is limited due to the poor water
solubility, pH instability, light instability, and skin permeation. The aim of
the present work was applying essential oil-based microemulsions to improve the
solubility, pH stability, photostability, and skin permeation of quercetin for
topical application. Peppermint oil (PO-ME), clove oil (CO-ME), and rosemary oil
(RMO-ME) were selected as model essential oils. Microemulsions composed of
Cremophor EL/1,2-propanediol/essential oils (47:23:30, w/w) were selected as
model formulations, based on the pseudo-ternary phase diagram and the
characterizations. In the solubility study, the solubility of quercetin was
improved dozens of times by microemulsions. Quercetin was found instable under
alkaline condition, with 50% degraded in the solution of pH 13. However, PO-ME,
CO-ME, and RMO-ME could protect quercetin from the hydroxide ions, with 47, 9,
and 12% of quercetin degraded. In the photostability study, the essential oil
based microemulsions showed the capability of protecting quercetin from
degradation under UV radiation. Where more than 67% of quercetin was degraded in
aqueous solution, while less than 7% of quercetin degraded in microemulsions. At
last, the in vitro skin permeation study showed that the essential oil-based
microemulsions could enhance the permeation capacity of quercetin by 2.5-3 times
compared to the aqueous solution. Hence, the prepared essential oil
microemulsions could improve the solubility, pH stability, photostability, and
skin permeation of quercetin, which will be beneficial for its topical
application.
PMID- 28516412
TI - Optimization of Adhesive Pastes for Dental Caries Prevention.
AB - Dental caries prevention products available on the market contain only
remineralizing agents or antibacterial agents. This study aimed to develop
adhesive pastes containing calcium phosphate and alpha-mangostin for dental
caries prevention using the optimization technique. Calcium phosphate was used as
a remineralizing agent, and extracted alpha-mangostin was used as an
antibacterial agent. The effect of the independent variables, which were fumed
silica, Eudragit(r) EPO, polyethylene glycol, and ethyl alcohol, on the responses
was investigated. The drying time, erosion rate, calcium release rate, and alpha
mangostin release rate were established as the measured responses. An equation
and a model of the relationship were constructed. An optimal formulation was
obtained, and its effect on dental caries prevention was investigated using the
pH-cycling model. The quadratic equation revealed that the drying time, calcium
release rate, and alpha-mangostin release rate tended to decrease when increasing
the fumed silica and decreasing other factors. The erosion rate tended to
increase when decreasing Eudragit(r) EPO and increasing other factors. The
observed responses of the optimal adhesive pastes were not significantly
different from the predicted responses. This result demonstrated that
optimization is an efficient technique in the formulation development of the
adhesive pastes. In addition, the optimal adhesive pastes could enhance acid
resistance activity to the tooth enamel.
PMID- 28516413
TI - Self-emulsification of Lipidic Drug Delivery System in Pure Water and in
Concentrated Glycerol Solution.
AB - Self-emulsifying drug delivery systems (SEDDS), often intended for oral delivery,
are normally explored in biorelevant aqueous media. The high complexity of these
multi-component systems leaves the understanding of self-emulsification poor,
hindering formulation rationalization. In this work, we aimed to fill this gap by
studying the effects of glycerol on the self-emulsification of a ternary
component formulation made of 20% w/w Tween 80, 15% w/w Span 80, and 65% w/w
Captex 300 Low C6. The behavior of SEDDS in pure water and a binary mixture of
water and glycerol (58.8% w/w) were investigated by optical microscopy, SAXS
(small angle X-ray scattering), dynamic light scattering, and surface tension
measurements. The presence of glycerol, at 58.8% w/w, altered the self
emulsification behavior by suppressing the formation of lamellar structures
observed in the presence of water, reducing the droplet mean diameter from 0.2 to
0.1 MUm and changing the mechanism of self-emulsification. As co-surfactant,
glycerol may intercalate within the polyoxyethylene chains of the surfactant at
the palisade layer, increasing the interface flexibility and expanding it. Since
no free water is available at the investigated glycerol concentration, glycerol,
which is also a co-solvent, may additionally modify long-range interactions by
reducing Van-der-Waals attractions or giving rise to repulsive surface-solvent
mediated forces of entropic origin. These effects could be exploited to
rationalize SEDDS formulations, widening their use within the pharmaceutical
industry.
PMID- 28516414
TI - Optimized Mucoadhesive Coated Niosomes as a Sustained Oral Delivery System of
Famotidine.
AB - The objective of this study is to develop an oral formulation of famotidine
niosomes coated with a mucoadhesive polymer, chitosan. Famotidine (FMT) has low
oral bioavailability of 40-45% and short half-life between 2.5 to 4 h. Famotidine
is classified as class IV in BCS because of its low aqueous solubility (0.1% w/v)
and low permeability. Thus, FMT was loaded to the bioadhesive coated niosomes to
improve its solubility, enhance its oral bioavailability, and sustain FMT release
pattern. Different formulations were prepared by thin-film hydration method and
characterized in terms of entrapment efficiency, morphological features, vesicle
size, and zeta potential. In vitro release and ex vivo permeability of famotidine
from the formulations were evaluated. The optimized formula was coated with
chitosan and its mucoadhesion and stability in bile salt was tested. The
optimized formula showed a high entrapment efficiency of 74%, as well sustained
the in vitro release of FMT in the simulated gastric medium and enhanced its
permeation through an excised goat's intestinal membrane by 1.4 fold in
comparison to FMT control suspension. The mucoadhesive coated formula exhibited a
significantly higher (p < 0.05) mucoadhesive efficiency and more stability in the
bile salt as compared to the uncoated formula. Therefore, it could be considered
as an efficient delivery system to maintain the prolonged release of FMT and
improve its oral bioavailability.
PMID- 28516415
TI - Signal Amplification Technologies for the Detection of Nucleic Acids: from Cell
Free Analysis to Live-Cell Imaging.
AB - Due to their unique properties, such as programmability, ligand-binding
capability, and flexibility, nucleic acids can serve as analytes and/or
recognition elements for biosensing. To improve the sensitivity of nucleic acid
based biosensing and hence the detection of a few copies of target molecule,
different modern amplification methodologies, namely target-and-signal-based
amplification strategies, have already been developed. These recent signal
amplification technologies, which are capable of amplifying the signal intensity
without changing the targets' copy number, have resulted in fast, reliable, and
sensitive methods for nucleic acid detection. Working in cell-free settings,
researchers have been able to optimize a variety of complex and quantitative
methods suitable for deploying in live-cell conditions. In this study, a
comprehensive review of the signal amplification technologies for the detection
of nucleic acids is provided. We classify the signal amplification methodologies
into enzymatic and non-enzymatic strategies with a primary focus on the methods
that enable us to shift away from in vitro detecting to in vivo imaging. Finally,
the future challenges and limitations of detection for cellular conditions are
discussed.
PMID- 28516416
TI - Anaerobic Digestion of Sugarcane Vinasse Through a Methanogenic UASB Reactor
Followed by a Packed Bed Reactor.
AB - The anaerobic treatment of raw vinasse in a combined system consisting in two
methanogenic reactors, up-flow anaerobic sludge blanket (UASB) + anaerobic packed
bed reactors (APBR), was evaluated. The organic loading rate (OLR) was varied,
and the best condition for the combined system was 12.5 kg COD m-3day-1 with
averages of 0.289 m3 CH4 kg COD r-1for the UASB reactor and 4.4 kg COD m-3day-1
with 0.207 m3 CH4 kg COD r-1 for APBR. The OLR played a major role in the
emission of H2S conducting to relatively stable quality of biogas emitted from
the APBR, with H2S concentrations <10 mg L-1. The importance of the sulphate to
COD ratio was demonstrated as a result of the low biogas quality recorded at the
lowest ratio. It was possible to develop a proper anaerobic digestion of raw
vinasse through the combined system with COD removal efficiency of 86.7% and
higher CH4 and a lower H2S content in biogas.
PMID- 28516417
TI - Microbial Lipid Production from Enzymatic Hydrolysate of Pecan Nutshell
Pretreated by Combined Pretreatment.
AB - Biodiesel is a fuel composed of monoalkyl esters of long-chain fatty acids
derived from renewable biomass sources. In this study, biomass waste pecan
nutshell (PS) was attempted to be converted into microbial oil. For effective
utilization of PS, sequential pretreatment with ethylene glycol-H2SO4-water
(78:2:20, wt:wt:wt) at 130 degrees C for 30 min and aqueous ammonia (25 wt%) at
50 degrees C for 24 h was used to enhance its enzymatic saccharification.
Significant linear correlation was obtained about delignification
saccharification (R 2 = 0.9507). SEM and FTIR results indicated that combination
pretreatment could effectively remove lignin and xylan in PS for promoting its
enzymatic saccharification. After 72 h, the reducing sugars from the hydrolysis
of 50 g/L pretreated PS by combination pretreatment could be obtained at 73.6%
yield. Using the recovered PS hydrolysates containing 20 g/L glucose as carbon
source, microbial lipids produced from the PS hydrolysates by Rhodococcus opacus
ACCC41043. Four fatty acids including palmitic acid (C16:0; 23.1%), palmitoleic
acid (C16:1; 22.4%), stearic acid (C18:0; 15.3%), and oleic acid (C18:1; 23.9%)
were distributed in total fatty acids. In conclusion, this strategy has potential
application in the future.
PMID- 28516418
TI - Improvement of the Stabilization and Activity of Protocatechuate 3,4-Dioxygenase
Isolated from Rhizobium sp. LMB-1 and Immobilized on Fe3O4 Nanoparticles.
AB - Protocatechuate 3,4-dioxygenase (P34O), which is isolated from Rhizobium sp. LMB
1, catalyzes the ring cleavage step in the metabolism of aromatic compounds, and
has great potential for environmental bioremediation. However, its structure is
very sensitive to different environmental factors, which weaken its activity.
Immobilization of the enzyme can improve its stability, allow reusability, and
reduce operation costs. In this work, the relative molecular mass of the native
P34O enzyme was determined to be 500 kDa by gel filtration chromatography on
Sephadex G-200, and the enzyme was immobilized onto (3-aminopropyl)
triethoxysilane-modified Fe3O4 nanoparticles (NPs) by the glutaraldehyde method.
The optimum pH of immobilized and free P34O was unaffected, but the optimum
temperature of immobilized P34O increased from 60 to 70 degrees C, and the
thermal stability of immobilized P34O was better than that of the free enzyme and
showed higher enzymatic activity at 60 and 70 degrees C. In addition, with the
exception of Fe3+, most metal ions and organic chemicals could not improve the
activity of free and immobilized P34O. The kinetic parameters of the immobilized
P34O were higher than those of the free enzyme, and immobilized P34O on Fe3O4 NPs
could be reused ten times without a remarkable decrease in enzymatic activity.
PMID- 28516420
TI - Event models and the fan effect.
AB - The current study explored the persistence of event model organizations and how
this influences the experience of interference during retrieval. People in this
study memorized lists of sentences about objects in locations, such as "The
potted palm is in the hotel." Previous work has shown that such information can
either be stored in separate event models, thereby producing retrieval
interference, or integrated into common event models, thereby eliminating
retrieval interference. Unlike prior studies, the current work explored the
impact of forgetting up to 2 weeks later on this pattern of performance. We
explored three possible outcomes across the various retention intervals. First,
consistent with research showing that longer delays reduce proactive and
retroactive interference, any retrieval interference effects of competing event
models could be reduced over time. Second, the binding of information into events
models may weaken over time, causing interference effects to emerge when they had
previously been absent. Third, and finally, the organization of information into
event models could remain stable over long periods of time. The results reported
here are most consistent with the last outcome. While there were some minor
variations across the various retention intervals, the basic pattern of event
model organization remained preserved over the two-week retention period.
PMID- 28516422
TI - A Mixed Methods Study of Barriers to Formal Diagnosis of Autism Spectrum Disorder
in Adults.
AB - Delayed diagnosis of autism spectrum disorder (ASD) into adulthood is common, and
self-diagnosis is a growing phenomenon. This mixed methods study aimed to explore
barriers to formal diagnosis of ASD in adults. In a qualitative strand, secondary
analysis of data on the experiences of 114 individuals who were self-diagnosed or
formally diagnosed with ASD in adulthood was used to identify barriers. In a
quantitative strand, 665 individuals who were self-diagnosed or formally
diagnosed in adulthood were surveyed online to examine incidence and severity of
barriers. Fear of not being believed by professionals was identified as the most
frequently occurring and most severe barrier. Professionals must strategize to
build trust with individuals with ASD, particularly when examining the accuracy
of self-diagnosis.
PMID- 28516421
TI - Differential Fairness Decisions and Brain Responses After Expressed Emotions of
Others in Boys with Autism Spectrum Disorders.
AB - Little is known about how emotions expressed by others influence social decisions
and associated brain responses in autism spectrum disorders (ASD). We
investigated the neural mechanisms underlying fairness decisions in response to
explicitly expressed emotions of others in boys with ASD and typically developing
(TD) boys. Participants with ASD adjusted their allocation behavior in response
to the emotions but reacted less unfair than TD controls in response to
happiness. We also found reduced brain responses in the precental gyrus in the
ASD versus TD group when receiving happy versus angry reactions and autistic
traits were positively associated with activity in the postcentral gyrus. These
results provide indications for a role of precentral and postcentral gyrus in
social-affective difficulties in ASD.
PMID- 28516424
TI - Differing Developmental Trajectories in Heart Rate Responses to Speech Stimuli in
Infants at High and Low Risk for Autism Spectrum Disorder.
AB - We investigated heart rate (HR) in infants at 3, 6, 9, and 12 months of age, at
high (HRA) and low (LRC) familial risk for ASD, to identify potential
endophenotypes of ASD risk related to attentional responses. HR was extracted
from functional near-infrared spectroscopy recordings while infants listened to
speech stimuli. Longitudinal analysis revealed that HRA infants and males
generally had lower baseline HR than LRC infants and females. HRA infants showed
decreased HR responses to early trials over development, while LRC infants showed
increased responses. These findings suggest altered developmental trajectories in
physiological responses to speech stimuli over the first year of life, with HRA
infants showing less social orienting over time.
PMID- 28516423
TI - Exploring the Components of Advanced Theory of Mind in Autism Spectrum Disorder.
AB - Performance of a group of 35 youth and adults with High-Functioning Autism (HFA)
was compared with a typical developing (TD) group on three Advanced Theory of
Mind tests. The distinction between the social-cognitive and social-perceptual
components of Theory of Mind was also explored. The HFA group had more
difficulties in all tasks. Performance on the two social-cognitive tests was
highly correlated in the HFA group, but these were not related with the social
perceptual component. These results suggest that the youth with HFA have
difficulties on all the components of social knowledge but may be using different
underlying cognitive abilities depending on the nature of the task.
PMID- 28516425
TI - A Screening Tool to Measure Eye Contact Avoidance in Boys with Fragile X
Syndrome.
AB - We examined the reliability, validity and factor structure of the Eye Contact
Avoidance Scale (ECAS), a new 15-item screening tool designed to measure eye
contact avoidance in individuals with fragile X syndrome (FXS). Internal
consistency of the scale was acceptable to excellent and convergent validity with
the Social Responsiveness Scale, Second Edition (SRS-2) and the Anxiety,
Depression, and Mood Scale (ADAMS) was good. Boys with a comorbid ASD diagnosis
obtained significantly higher scores on the ECAS compared to boys without ASD,
when controlling for communication ability. A confirmatory factor analysis
indicated that a two-factor model (avoidance and aversion) provided an excellent
fit to the data. The ECAS appears to be a promising reliable and valid tool that
could be employed as an outcome measure in future pharmacological/behavioral
treatment trials for FXS.
PMID- 28516427
TI - The organism strikes back: Chlorella algae and their impact on photosynthesis
research, 1920s-1960s.
AB - Historians and philosophers of twentieth-century life sciences have demonstrated
that the choice of experimental organism can profoundly influence research
fields, in ways that sometimes undermined the scientists' original intentions.
The present paper aims to enrich and broaden the scope of this literature by
analysing the career of unicellular green algae of the genus Chlorella. They were
introduced for the study of photosynthesis in 1919 by the German cell
physiologist Otto H. Warburg, and they became the favourite research objects in
this field up to the 1960s. The paper argues that dealing with Chlorella's high
metabolic flexibility was crucial for the emergence of a new conception of
photosynthesis, as a plastic, integrated system of pathways. At the same time, it
led to new collaborations between physiologists and phycologists, both of whom
started to re-orient their studies in ecologically informed directions. Following
Chlorella's trail, hence, not only elucidates how experimental organisms forced
scientists to change their conceptual approaches and techniques, but also
provides insight into the interaction of different lines of research of mid
twentieth century plant sciences.
PMID- 28516428
TI - Cerebrovascular Angiogenic Reprogramming upon LRP1 Repression: Impact on
Sphingosine-1-Phosphate-Mediated Signaling in Brain Endothelial Cell
Chemotactism.
AB - Switches in sphingolipid metabolism have recently been associated with oncogenic
transformation, and a role for the low-density lipoprotein receptor-related
protein 1 (LRP1) in sphingosine-1-phosphate (S1P) proangiogenic signaling
inferred. S1P signaling crosstalk with LRP1 in brain microvascular endothelial
cells (HBMEC) is however unclear. Transient in vitro siLRP1 gene silencing was
compared to stable shLRP1 knockdown. We observed decreased expression of
CCAAT/enhancer binding protein beta (C/EBPbeta), a transcription factor for which
multiple binding sites are found within the promoter sequences of all five S1P
receptor members, upon stable but not transient LRP1 repression. Chemotactic
migration of brain EC isolated from Lrp1(EC)-/- mice and of stable shLRP1 HBMEC
became unresponsive to S1P, partly due to altered ERK and p38 MAPK pathways,
whereas chemotactism remained unaltered following transient in vitro siLRP1
repression. Diminished S1P1, S1P3, and S1P5 expression were observed in stable
shLRP1 HBMEC and in brain EC isolated from Lrp1(EC)-/- mice. Overexpression of
LRP1 cluster IV rescued S1P-mediated cell migration through increased S1P3
transcription in shLRP1 HBMEC. Our study highlights an adaptive signaling
crosstalk between LRP1 and specific S1P receptors which may regulate the
angiogenic response of brain EC and be targeted at the blood-brain barrier in
future therapeutic strategies.
PMID- 28516426
TI - Characterization of Medication Use in a Multicenter Sample of Pediatric
Inpatients with Autism Spectrum Disorder.
AB - Nearly 11% of youth with Autism Spectrum Disorder (ASD) undergo psychiatric
hospitalization, and 65% are treated with psychotropic medication. Here we
characterize psychotropic medication usage in subjects enrolled in the Autism
Inpatient Collection. Participant psychotropic medication usage rates topped 90%
at admission and discharge, though there was a decline at 2-month follow-up.
Antipsychotics, ADHD medications, and sleep aids were the most commonly reported
classes of medications. The impact of age, gender, and non-verbal IQ on
medication usage rates was minimal, though age and IQ may play a role in
prescribing practices. Future work is indicated to explore medication usage
trends, the impact of clinical factors on medication use rates, and the safety of
psychotropic medications in youth with ASD.
PMID- 28516419
TI - Abstracts of the 52nd Workshop for Pediatric Research : Frankfurt, Germany. 27-28
October 2016.
PMID- 28516429
TI - Cardinal Epigenetic Role of non-coding Regulatory RNAs in Circadian Rhythm.
AB - Circadian rhythm which governs basic physiological activities like sleeping,
feeding and energy consumption is regulated by light-controlled central clock
genes in the pacemaker neuron. The timekeeping machinery with unique
transcriptional and post-transcriptional feedback loops is controlled by
different small regulatory RNAs in the brain. Roles of the multiple neuronal
genes, especially post-transcriptional regulation, splicing, polyadenylation,
mature mRNA editing, and stability of translation products, are controlled by
epigenetic activities orchestrated via small RNAs. Collectively, these mechanisms
regulate clock and light-controlled genes for effecting pacemaker activity and
entrainment. Regulatory small RNAs of the circadian circuit, timekeeping
mechanism, synchronization of regular entrainment, oscillation, and rhythmicity
are regulated by diversified RNA molecules. Regulatory small RNAs operate
critical roles in brain activities including the neuronal clock activity. In this
report, we propose the emergence of the earlier unexpected small RNAs for a
historic perspective of epigenetic regulation of the brain clock system.
PMID- 28516430
TI - Ramelteon Improves Post-traumatic Stress Disorder-Like Behaviors Exhibited by
Fatty Acid-Binding Protein 3 Null Mice.
AB - We previously reported that fatty acid-binding protein 3 (FABP3) knockout (Fabp3
/-) mice exhibit abnormal dopamine-related behaviors such as enhanced dopamine D2
receptor antagonist-induced catalepsy behaviors. Here, we report that Fabp3 null
mice exhibit cognitive deficits, hyperlocomotion and impaired fear extinction,
and thus show post-traumatic stress disorder (PTSD)-like behaviors. Notably,
chronic administration of ramelteon (1.0 mg/kg, p.o.), a melatonin receptor
agonist, improved all PTSD-like behaviors tested in Fabp3 -/- mice. Relevant to
mechanisms underlying impaired fear extinction, we observed significantly reduced
levels of Ca2+/calmodulin-dependent protein kinase II (CaMKII)
autophosphorylation without changes in ERK phosphorylation in the anterior
cingulate cortex (ACC). Inversely, CaMKII autophosphorylation increased in the
basolateral amygdala (BLA) but remained relatively unchanged in hippocampus of
Fabp3 -/- mice. Likewise, the number of c-Fos-positive neurons in BLA
significantly increased after exposure to contextual fear conditions but remained
unchanged in the central nucleus of the amygdala (CeA). Importantly, chronic
ramelteon administration (1.0 mg/kg, p.o.) restored abnormal c-Fos expression and
CaMKII autophosphorylation in the ACC and BLA of Fabp3 -/- mice. Finally, the
melatonin receptor antagonist luzindole (2.5 mg/kg, i.p.) blocked ramelteon
dependent improvements. Taken together, Fabp3 -/- mice show PTSD-like behaviors,
and ramelteon is a likely attractive candidate for PTSD therapy.
PMID- 28516432
TI - Measurement of piperacillin plasma concentrations in cancer patients with
suspected infection.
AB - BACKGROUND: Piperacillin (PIP) in combination with tazobactam is commonly used
for anti-infective treatment in cancer patients. PIP exerts a time-dependent
killing. Thus, the maintenance of plasma concentrations above a pre-defined
target concentration for a pre-defined time may be relevant for optimal efficacy.
It is assumed that PIP-plasma concentrations above the clinical breakpoint of the
target pathogen [Pseudomonas aeruginosa, clinical breakpoint at minimal
inhibitory concentration (MIC) 16 mg/L] should be reached for 100% of the dosing
interval or >4xMIC (64 mg/L) for 50% of the dosing interval. Whereas studies in
the intensive-care setting have shown underdosing in patients with sepsis, little
is known about PIP-plasma concentrations in cancer patients. METHODS: Data of 56
cancer patients who received piperacillin/tazobactam (PIP/TAZ, 4.5 g three times
daily) as empiric therapy for suspected infection were analysed at baseline and 4
h after the infusion. RESULTS: Median trough concentrations in steady state
[median 3 days (IQR 3-5) after start of PIP/TAZ] were 4.6 mg/L (95% CI 0.3-136.3)
and median PIP-plasma concentrations 4 h after infusion were 46.2 mg/L (95% CI
10.1-285.6). A second evaluation 5 days (IQR 4-7) after start of PIP/TAZ
confirmed these results: trough concentrations were 2.7 mg/L (95% CI 0.5-6.3),
concentrations after 4 h 28.0 mg/L (95% CI 1.7-47.3). A good renal function was
associated with lower plasma concentrations (r = -0.388, p < 0.003). Detailed
pharmacokinetic measurements in six patients showed low maximum plasma
concentration (median 165 mg/L) and a rapid decline of plasma concentrations
(median plasma half time 1.38 h). CONCLUSION: In conclusion, piperacillin plasma
concentrations in cancer patients are below target levels warranting prospective
trials to investigate therapeutic drug monitoring.
PMID- 28516433
TI - With Decades of Perspective, Craig Henderson Observes That Treatment of Breast
Cancer Has Come a Long Way.
PMID- 28516434
TI - Gross Hematuria and Suspicious Bladder Lesions in a 52-Year-Old North African
Immigrant.
PMID- 28516435
TI - Management Considerations in Cancer Patients With Rheumatoid Arthritis.
AB - Rheumatoid arthritis is a common inflammatory disease that requires treatment
with immunosuppressants to control symptoms and avoid joint destruction. Managing
cancer in patients with concomitant rheumatoid arthritis poses special challenges
that require close coordination of care between oncologists and rheumatologists.
Potential clinical issues needing special consideration include: 1) perioperative
management in patients undergoing cancer surgery, which often requires
discontinuation of antirrheumatic therapy; 2) use of immunosuppressant therapies
for rheumatoid arthritis, especially biologic agents that inhibit cytokine and
immune pathways, which conceivably could affect immune-mediated antitumor
responses (the issues are different in patients with active cancer vs those with
a past history of cancer and no recurrences); 3) management in the palliative
care setting; and 4) use of cancer immunotherapy, such as checkpoint inhibitor
agents, in patients with pre-existing rheumatoid arthritis. We explore these
clinical issues in case-based scenarios. In all cases, clinical decision making
must include a careful weighing of risks and benefits of both cancer treatments
and antirrheumatic therapies, with attention given to prognosis and life
expectancy, quality of life, and patient preferences.
PMID- 28516436
TI - The Growing Challenge of Young Adults With Colorectal Cancer.
AB - Although the incidence of colorectal cancer is declining in the overall US
population, the rates of colorectal cancer are rising among adolescent and young
adult (AYA) patients-defined as individuals under 45 years of age. This
population includes patients deemed too young for routine colorectal cancer
screening, which in the United States is typically initiated at age 50 for men
and women at average risk. Clinicopathologic differences have long been observed
between AYAs and older patients with colorectal cancer. In addition, recently
available high-throughput DNA sequencing techniques have revealed different rates
of genetic alterations between these two groups, indicating potential molecular
differences in the disease state and suggesting the need for alternative
treatment strategies in younger patients. AYA patients with colorectal cancer
often receive more aggressive treatment regimens than their older counterparts,
without a corresponding improvement in survival. Furthermore, these younger
patients have particular survivorship issues that warrant attention from the
oncology community. In this review, we address specific issues pertaining to AYA
patients with colorectal cancer, including evaluation for hereditary colorectal
cancer syndromes, clinicopathologic and biologic features unique to AYA patients
with colorectal cancer, treatment outcomes, and survivorship.
PMID- 28516437
TI - Point/Counterpoint: Is Lymphadenectomy Required in Endometrial Cancer for
Adequate Surgical Staging?
PMID- 28516438
TI - Point/Counterpoint: Is Lymphadenectomy Required in Endometrial Cancer for
Adequate Surgical Staging?
PMID- 28516439
TI - Reassessment of Anti-CD20 Therapy in Lymphoid Malignancies: Impact, Limitations,
and New Directions.
AB - The addition of anti-CD20 monoclonal antibodies to the treatment of B-cell
malignancies has dramatically affected the field as well as the lives of
patients. Rituximab in particular has been combined safely with conventional
chemotherapy and has resulted in improved overall survival in major histologic
subtypes of B-cell lymphoma and chronic lymphocytic leukemia. It is incorporated
into the standard initial treatment of nearly all of these diseases. Novel anti
CD20 antibodies are currently under development. Two of these agents, ofatumumab
and obinutuzumab, have been approved for use in certain clinical settings.
Research comparing these newer antibodies with rituximab is ongoing. As these
newer antibodies are further studied and developed, improvements in response and
progression-free survival need to be considered in the context of clinical
benefit as well as toxicity, especially in indolent diseases. Research involving
rituximab biosimilars is ongoing as well, and recent preliminary data demonstrate
similar efficacy and tolerability when compared with rituximab. An additional
focus of ongoing research is the use of extended schedules of anti-CD20
monoclonal antibodies, as the optimal duration of therapy remains ill-defined in
many histologic subtypes. To maximize the use of these agents, well-validated
clinical trial endpoints will need to be carefully considered.
PMID- 28516440
TI - The Uncertainties of Rituximab and Related Therapies, 20 Years After Approval.
PMID- 28516441
TI - Decision Making in the Surgical Management of Invasive Breast Cancer-Part 2:
Expanded Applications for Breast-Conserving Surgery.
AB - Treatment of early-stage invasive breast cancer with breast-conserving surgery
plus radiation therapy (RT) yields overall survival outcomes equivalent to those
achieved with mastectomy. Further, breast-conserving surgery is endorsed by the
National Comprehensive Cancer Network as being supported by the highest-level,
category 1 evidence. Advances in pathologic evaluation, management of multiple
tumors, oncoplastic lumpectomy techniques, neoadjuvant chemotherapy, and
hypofractionated RT can expand the pool of patients eligible for breast
conserving surgery. Selected patients (for example, patients older than 70 years
of age with hormone receptor-positive T1 tumors who are willing to commit to
receiving adjuvant endocrine therapy) may be able to forgo RT completely. This
article will detail current management approaches to achieving breast
conservation in patients with invasive breast cancer, including cases of bulky
tumors and/or multiple tumors.
PMID- 28516431
TI - A Comparison of Neuroimaging Abnormalities in Multiple Sclerosis, Major
Depression and Chronic Fatigue Syndrome (Myalgic Encephalomyelitis): is There a
Common Cause?
AB - There is copious evidence of abnormalities in resting-state functional network
connectivity states, grey and white matter pathology and impaired cerebral
perfusion in patients afforded a diagnosis of multiple sclerosis, major
depression or chronic fatigue syndrome (CFS) (myalgic encephalomyelitis).
Systemic inflammation may well be a major element explaining such findings. Inter
patient and inter-illness variations in neuroimaging findings may arise at least
in part from regional genetic, epigenetic and environmental variations in the
functions of microglia and astrocytes. Regional differences in neuronal
resistance to oxidative and inflammatory insults and in the performance of
antioxidant defences in the central nervous system may also play a role.
Importantly, replicated experimental findings suggest that the use of high
resolution SPECT imaging may have the capacity to differentiate patients afforded
a diagnosis of CFS from those with a diagnosis of depression. Further research
involving this form of neuroimaging appears warranted in an attempt to overcome
the problem of aetiologically heterogeneous cohorts which probably explain
conflicting findings produced by investigative teams active in this field.
However, the ionising radiation and relative lack of sensitivity involved
probably preclude its use as a routine diagnostic tool.
PMID- 28516442
TI - Vaccines for the common cold.
AB - BACKGROUND: The common cold is a spontaneously remitting infection of the upper
respiratory tract, characterised by a runny nose, nasal congestion, sneezing,
cough, malaise, sore throat, and fever (usually < 37.8o C). The widespread
morbidity caused by the common cold worldwide is related to its ubiquitousness
rather than its severity. The development of vaccines for the common cold has
been difficult because of antigenic variability of the common cold virus and the
indistinguishable multiple other viruses and even bacteria acting as infective
agents. There is uncertainty regarding the efficacy and safety of interventions
for preventing the common cold in healthy people. This is an update of a Cochrane
review first published in 2011 and previously updated in 2013. OBJECTIVES: To
assess the clinical effectiveness and safety of vaccines for preventing the
common cold in healthy people. SEARCH METHODS: We searched the Cochrane Central
Register of Controlled Trials (CENTRAL) (September 2016), MEDLINE (1948 to
September 2016), Embase (1974 to September 2016), CINAHL (1981 to September
2016), and LILACS (1982 to September 2016). We also searched three trials
registers for ongoing studies and four websites for additional trials (February
2017). We included no language or date restrictions. SELECTION CRITERIA:
Randomised controlled trials (RCTs) of any virus vaccines compared with placebo
to prevent the common cold in healthy people. DATA COLLECTION AND ANALYSIS: Two
review authors independently evaluated methodological quality and extracted trial
data. We resolved disagreements by discussion or by consulting a third review
author. MAIN RESULTS: We found no additional RCTs for inclusion in this update.
This review includes one RCT dating from the 1960s with an overall high risk of
bias. The RCT included 2307 healthy participants, all of whom were included in
analyses. This trial compared the effect of an adenovirus vaccine against
placebo. No statistically significant difference in common cold incidence was
found: there were 13 (1.14%) events in 1139 participants in the vaccines group
and 14 (1.19%) events in 1168 participants in the placebo group (risk ratio 0.95,
95% confidence interval 0.45 to 2.02; P = 0.90). No adverse events related to the
live vaccine were reported. The quality of the evidence was low due to
limitations in methodological quality and a wide 95% confidence interval.
AUTHORS' CONCLUSIONS: This Cochrane Review was based on one study with low
quality evidence. We found no conclusive results to support the use of vaccines
for preventing the common cold in healthy people compared with placebo. We
identified a need for well-designed, adequately powered RCTs to investigate
vaccines for the common cold in healthy people. Any future trials on medical
treatments for preventing the common cold should assess a variety of virus
vaccines for this condition. Outcome measures should include common cold
incidence, vaccine safety, and mortality related to the vaccine.
PMID- 28516443
TI - Multiple red blood cell transfusions and iron overload in very low birthweight
infants.
AB - BACKGROUND AND OBJECTIVES: To estimate the risk of iron overload in very low
birthweight (VLBW) infants who receive more than two red blood cell (RBC)
transfusions, in comparison with those who receive two or less during their
hospital stay. MATERIALS AND METHODS: Prospective open cohort study in VLBW
infants with >2 (exposed) and <=2 (non-exposed) RBC transfusions. Ferritin,
alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured
at birth and after each RBC transfusion. The incidence of iron overload was
determined. Risk factors were analysed using a logistic regression model. RBC
transfusion volume correlations with ferritin, ALT and AST were calculated with
Spearman's rank correlation coefficient, as well as correlations between ferritin
and aminotransferases. RESULTS: A total of 63 patients were enrolled, 18 of which
were exposed and 45 non-exposed. Twelve patients developed severe iron overload,
eight exposed (44.5%) vs. four (8.8%) non-exposed (RR: 5, 95% CI: 1.7-14.6).
Multivariate analysis showed that the number of transfusions increased the risk
of iron overload (OR: 2.07, 95% CI: 1.36-2.14) while a higher one-minute Apgar
score was associated with a lower risk (OR: 0.56, 95% CI: 0.32-0.99). Severe iron
overload mainly occurred with a transfusion volume higher than 120 ml/kg. There
was a positive correlation between ferritin and transfusion (r = 0.53; P <
0.001). CONCLUSION: There was a higher risk of iron overload in exposed infants
in comparison with non-exposed infants. Severe iron overload in VLBW infants may
occur with a total transfusion volume >120 ml/kg.
PMID- 28516444
TI - Toxicological Analysis of Opiates from Alternative Matrices Collected from an
Exhumed Body.
AB - In this case study, the body of a 45-year-old man was exhumed after 1 year at the
request of the public prosecutor to assess whether the death was caused by drug
consumption. Toxicological analyses were performed on several matrices, including
liver, kidney, and the alternative matrices hair and teeth. The systematic
toxicological analysis (STA), which consisted of basic and acid liquid/liquid
extraction and gas chromatography-mass spectrometry (GC-MS) analysis, showed the
presence of opiates in each of the matrices analyzed. Subsequently, to confirm
and quantify the presence of opioids, samples of each of the matrices were
subjected to solid-phase extraction and specific GC-MS analysis. The case
presented demonstrates the possibility of drug detection in an exhumed body that
has been buried for 1 year, despite the problems of quantitative interpretation
of the data, and that toxicological results could be useful along with other
forensic evidence.
PMID- 28516447
TI - Metacarpophalangeal joint injury patterns on magnetic resonance imaging: A
comparison in racing Standardbreds and Thoroughbreds.
AB - The metacarpal condyle has received extensive attention as a predominant site of
overload arthropathy in racehorses. However, detailed descriptions of MRI lesion
patterns for the metacarpophalangeal joint and comparisons between types of
racing horses are currently lacking. Aims of this retrospective, cross-sectional
study were to describe and compare standing low-field magnetic resonance findings
in the metacarpophalangeal joints for groups of Standardbreds and Thoroughbreds
using systematic semiquantitative scores. Data archives at the Clinique
Veterinaire Equine de Chantilly and Imavet were searched during the period from
June 2010 to February 2016. Images were retrieved and reviewed by one reader. A
total of 30 Standardbreds and 77 Thoroughbreds were sampled. The Thoroughbreds
developed a much higher rate of stress fractures (40.3% vs. 10%) and overall more
severe scores of subchondral sclerosis and bone marrow lesions than
Standardbreds. The Standardbreds had more sites of subchondral bone defect and
resorption, as well as higher synovitis and joint capsule thickening scores. Both
Standardbreds and Thoroughbreds frequently developed multifocal subchondral
lesions not limited to the distal palmar condyle. The Standardbreds had a higher
tendency to develop dorsomedial joint pole subchondral injuries. Both
Standardbreds and Thoroughbreds developed a noticeably high rate of periarticular
soft tissue injuries (36.7% in Standardbreds and 20.8% in Thoroughbreds), which
were rarely considered as the main contributors to the lameness. Findings
supported the use of low-field MRI as a whole-organ assessment tool for
Standardbreds and Thoroughbreds with suspected metacarpophalangeal joint
injuries.
PMID- 28516445
TI - Role of the endocannabinoid system in vertebrates: Emphasis on the zebrafish
model.
AB - The endocannabinoid system (eCBs), named after the plant Cannabis sativa,
comprises cannabinoid receptors, endogenous ligands known as "endocannabinoids",
and enzymes involved in the biosynthesis and degradation of these ligands, as
well as putative transporters for these ligands. ECBs proteins and small
molecules have been detected in early embryonic stages of many vertebrate models.
As a result, cannabinoid receptors and endogenous as well as exogenous
cannabinoids influence development and behavior in many vertebrate species.
Understanding the precise mechanisms of action for the eCBs will provide an
invaluable guide towards elucidation of vertebrate development and will also help
delineate how developmental exposure to marijuana might impact health and
cognitive/executive functioning in adulthood. Here we review the developmental
roles of the eCBs in vertebrates, focusing our attention on the zebrafish model.
Since little is known regarding the eCBs in zebrafish, we provide new data on the
expression profiles of eCBs genes during development and in adult tissue types of
this model organism. We also highlight exciting areas for future investigations,
including the synaptic regulation of eCBs, its role in reward and addiction, and
in nervous system development and plasticity.
PMID- 28516446
TI - Primary Human Lung Alveolus-on-a-chip Model of Intravascular Thrombosis for
Assessment of Therapeutics.
AB - Pulmonary thrombosis is a significant cause of patient mortality; however, there
are no effective in vitro models of thrombi formation in human lung microvessels
that could also assess therapeutics and toxicology of antithrombotic drugs. Here,
we show that a microfluidic lung alveolus-on-a-chip lined by human primary
alveolar epithelium interfaced with endothelium and cultured under flowing whole
blood can be used to perform quantitative analysis of organ-level contributions
to inflammation-induced thrombosis. This microfluidic chip recapitulates in vivo
responses, including platelet-endothelial dynamics and revealed that
lipopolysaccharide (LPS) endotoxin indirectly stimulates intravascular thrombosis
by activating the alveolar epithelium, rather than acting directly on
endothelium. This model is also used to analyze inhibition of endothelial
activation and thrombosis due to a protease activated receptor-1 (PAR-1)
antagonist, demonstrating its ability to dissect complex responses and identify
antithrombotic therapeutics. Thus, this methodology offers a new approach to
study human pathophysiology of pulmonary thrombosis and advance drug development.
PMID- 28516448
TI - Management and outcome of clinically evident neck recurrence in patients with
papillary thyroid cancer.
AB - BACKGROUND: The aim of this study was to report our incidence of clinically
evident neck recurrence, salvage neck management and subsequent outcomes in
patients with papillary thyroid cancer. This is important to know so that
patients with thyroid cancer can be properly counselled about the implications of
recurrent disease and subsequent outcome. METHODS: An institutional database of
3664 patients with thyroid cancer operated between 1986 and 2010 was reviewed.
Patients with nonpapillary histology and gross residual disease and those with
distant metastases at presentation or distant metastases prior to nodal
recurrence were excluded from the study. Of these, 99 (3.0%) patients developed
clinically evident nodal recurrence. Details of recurrence and subsequent therapy
were recorded for each patient. Subsequent disease-specific survival (sDSS),
distant recurrence-free survival (sDRFS) and nodal recurrence-free survival
(sNRFS) were determined from the date of first nodal recurrence using the Kaplan
Meier method. RESULTS: Of the 99 patients, 59% were female and 41% male. The
median age was 41 years (range 5-91). The majority of patients had pT3/4 primary
tumours (63%) and were pN+ (78%) at initial presentation. The median time to
clinically evident nodal recurrence was 28 months (range: 3-264). Nodal
recurrence occurred in the central neck in 15 (15%) patients, lateral neck in 74
(75%) patients and both in 10 (10%) patients. After salvage treatment, the 5-year
sDSS was 97.4% from time of nodal recurrence. The 5-year sDRFS and sNRFS were
89.2% and 93.7%, respectively. CONCLUSION: In our series, isolated clinically
evident nodal recurrence occurred in 3.0% of patients. Such patients are
successfully salvaged with surgery and adjuvant therapy with sDSS of 97.4% at 5
years.
PMID- 28516450
TI - Synthesis and multi-spectroscopic study on DNA-binding, cleavage and biological
properties of M(II) complexes based on N2 O2 donor Schiff base ligand.
AB - A novel Schiff base, (S,Z)-4-(methylthio)-2-((3-oxo-2,3-dihydro-1H-inden-1
ylidene)amino)butanoic acid (L) and four M(II) complexes (where M = Co, Cu, Ni
and Zn) were synthesized and characterized. The DNA-binding characteristics of
the complexes were investigated using various spectroscopic methods and viscosity
measurements. Analysis of the results suggests that all the complexes bind to
calf thymus DNA via intercalation. Among the four, Cu(II) complex was found to
promote the photocleavage of plasmid DNA pBR322 under irradiation at 365 nm.
These complexes also exhibit good antioxidant activities against 2,2-diphenyl-1
picrylhydrazyl radical. In vitro antibacterial and antifungal assay indicates
that these complexes are good antimicrobial agents.
PMID- 28516451
TI - Evidence that eating baked egg or milk influences egg or milk allergy resolution:
a systematic review.
AB - BACKGROUND: It has been proposed that the frequent ingestion of baked hen's egg
or cow's milk accelerates the resolution of hen's egg or cow's milk allergy. This
practice is being introduced into clinical practice. OBJECTIVE: To systematically
review the evidence to determine whether the introduction of baked hen's egg or
cow's milk into the diet of children with hen's egg or cow's milk allergies
respectively leads to a larger proportion of children outgrowing these allergies
than expected. METHODS: A systematic review of the literature was conducted in
Medline, Embase and CINAHL. The inclusion criteria were as follows: randomized
control trials, case-control or cohort studies; children aged 0-18 years with
hen's egg or cow's milk allergy; baked hen's egg or cow's milk intervention with
or without a comparator; and resolution of the hen's egg or cow's milk allergy as
determined by food challenge as the outcome. Studies were critically appraised
using the quality assessment tool for quantitative studies. PROSPERO reference
CRD42015026029. RESULTS: We identified 851 and 2816 hen's egg and cow's milk
articles respectively. Only three hen's egg and three cow's milk studies
fulfilled our pre-specified inclusion criteria. The studies concluded that baked
products either increased the likelihood of the resolution of allergy or
accelerated resolution. However, when critiqued, all studies were classified as
weak because they were observational, lacking an appropriate control group; this
brings into doubt the study's conclusions. There were a number of examples of
severe reactions to baked products. CONCLUSION: There is little evidence to
address the hypothesis that the ingestion of baked hen's egg or cow's milk
results in more patients outgrowing their hen's egg or cow's milk allergy
respectively. Data are required from a trial comparing the resolution rates of
baked-tolerant participants who are randomized to ingest or avoid baked products
to assess the accuracy of this hypothesis.
PMID- 28516453
TI - DBA/2J mouse model for experimental glaucoma: pitfalls and problems.
AB - BACKGROUND: The DBA/2J mouse has been described as a model for congenital
experimental glaucoma. It develops anterior segment anomalies with synechiae and
pigment dispersion leading to raised intraocular pressure and glaucomatous
damage. However, there are serious practical considerations when using this model
in longitudinal studies. METHODS: We followed 118 mice from 12-48 weeks of age in
a pharmaceutical trial. Here we report on the findings in control animals (n =
37). Intraocular pressure was measured weekly, electrophysiology and optical
coherence tomography every 6 weeks. A subset also had invasive intraocular
pressure measurements performed prior to euthanasia. RESULTS: Although
intraocular pressure eventually rose by 9 months in most animals, tonometry was
complicated by corneal calcification in the majority of animals rendering
intraocular pressure measurement unreliable. Invasive intraocular pressure did
not correlate with non-invasive measures. Loss of scotopic threshold response and
thinning of inner retinal layers on optical coherence tomography was observed
over time, suggesting glaucomatous damage, but this occurred in some animals
without raised intraocular pressure. Poor pupil dilation significantly affected
electrophysiology, optical coherence tomography and fundus imaging; 22% of
animals developed major systemic complications leading to high dropout rate.
CONCLUSIONS: The DBA/2J experimental glaucoma model shows variability in
expression, and its pathological changes cause major difficulties in assessing
disease progression. From our experience, the model presents significant
challenges for drug studies in glaucoma, as there are many confounding factors:
difficulty with accurate intraocular pressure measurement, in vivo imaging, and
electrophysiology recording and a high dropout rate. In addition, there may be an
underlying neurodegenerative process independent of intraocular pressure.
PMID- 28516452
TI - Correlation between socio-economic status and atopic dermatitis in Korean adults:
the Korea national health and nutrition examination survey (2007-2014).
AB - INTRODUCTION: Atopic dermatitis (AD) is one of the most common allergic diseases.
Its prevalence has been increasing in recent decades. Socio-economic status is
well-known risk factor of allergic diseases. OBJECTIVE: This study was performed
to investigate the relationship between socio-economic status and AD in Korean
adults. METHODS: Data were acquired from 47 351 men and women, >=19 years of age
who participated in the Korea National Health and Nutrition Examination Surveys
(KNHANES) conducted from 2007 to 2014. The presence of AD was based on self
reported physician diagnosis of AD in the Health Interview Surveys. RESULTS: The
prevalence of AD was 3.1%, which decreased with increasing age. In univariate
analysis, adults with AD were prone to be female, younger, never-married, well
educated, lower household members, and urban dwelling (all P < 0.01). Monthly
family income and smoking status were not associated with the presence of AD. The
prevalence of hypertension, diabetes mellitus and asthma was higher in AD
subjects (all P < 0.01), while obesity was not associated with adult AD. After
adjusting for confounders, logistic regression analysis showed female sex
(adjusted odds ratio [aOR]: 1.483, 95% CI: 1.268-1.734), age (P < 0.01), marital
status (Single: aOR: 1.307, 95% CI: 1.012-1.690; Never-married: aOR: 1.938, 95%
CI: 1.513-2.482), urban residence (aOR: 1.281, 95% CI: 1.045-1.569) and asthma
(aOR: 1.788, 95% CI: 1.416-2.258) were associated with higher prevalence of AD
(all P < 0.01). CONCLUSION: Female sex, age, marital status, urban residence, and
the presence of asthma are important risk factors of the prevalence of AD in
Korean adults.
PMID- 28516456
TI - Description of embryonic development and ultrastructure in miracidia of
Cardiocephaloides longicollis (Digenea, Strigeidae) in relation to active host
finding strategy in a marine environment.
AB - The functional ultrastructure and embryonic development of miracidia in naturally
released eggs of the trematode Cardiocephaloides longicollis were studied using
light and transmission electron microscopy. This species has operculated eggs and
embryogenesis occurs in the marine environment before an actively infecting
ciliated miracidium hatches. Six different developmental stages were identified.
The lack of pores in the eggshell indicates its impermeability and the
miracidium's dependency on glycogen nutritive reserves, contained in numerous
vitellocytes in early embryos. As the development advances, these merge into
larger vitelline vacuoles that encircle the miracidium and may aid its hatching.
Tissue and primary organ differentiation were observed in advanced stages, i.e.,
terebratorium, glands, cerebral ganglion, peripheral sensory endings, and
eyespots. The anterior part of the body contains a single apical and paired
lateral glands, as well as two types of sensory endings, which permit location,
adhesion, and penetration of the host. No previous studies describe the embryonic
development and ultrastructure of miracidia in strigeids, however, some of the
structural features shared with other, well described species with unknown life
cycles are emphasised. This study highlights that ultrastructural data have to be
interpreted in relation to parasite biology to understand the structural
requirements of specific parasite strategies.
PMID- 28516455
TI - Heterogeneity of Purkinje cell simple spike-complex spike interactions: zebrin-
and non-zebrin-related variations.
AB - KEY POINTS: Cerebellar Purkinje cells (PCs) generate two types of action
potentials, simple and complex spikes. Although they are generated by distinct
mechanisms, interactions between the two spike types exist. Zebrin staining
produces alternating positive and negative stripes of PCs across most of the
cerebellar cortex. Thus, here we compared simple spike-complex spike interactions
both within and across zebrin populations. Simple spike activity undergoes a
complex modulation preceding and following a complex spike. The amplitudes of the
pre- and post-complex spike modulation phases were correlated across PCs. On
average, the modulation was larger for PCs in zebrin positive regions.
Correlations between aspects of the complex spike waveform and simple spike
activity were found, some of which varied between zebrin positive and negative
PCs. The implications of the results are discussed with regard to hypotheses that
complex spikes are triggered by rises in simple spike activity for either motor
learning or homeostatic functions. ABSTRACT: Purkinje cells (PCs) generate two
types of action potentials, called simple and complex spikes (SSs and CSs). We
first investigated the CS-associated modulation of SS activity and its
relationship to the zebrin status of the PC. The modulation pattern consisted of
a pre-CS rise in SS activity, and then, following the CS, a pause, a rebound, and
finally a late inhibition of SS activity for both zebrin positive (Z+) and
negative (Z-) cells, though the amplitudes of the phases were larger in Z+ cells.
Moreover, the amplitudes of the pre-CS rise with the late inhibitory phase of the
modulation were correlated across PCs. In contrast, correlations between
modulation phases across CSs of individual PCs were generally weak. Next, the
relationship between CS spikelets and SS activity was investigated. The number of
spikelets/CS correlated with the average SS firing rate only for Z+ cells. In
contrast, correlations across CSs between spikelet numbers and the amplitudes of
the SS modulation phases were generally weak. Division of spikelets into likely
axonally propagated and non-propagated groups (based on their interspikelet
interval) showed that the correlation of spikelet number with SS firing rate
primarily reflected a relationship with non-propagated spikelets. In sum, the
results show both zebrin-related and non-zebrin-related physiological
heterogeneity in SS-CS interactions among PCs, which suggests that the cerebellar
cortex is more functionally diverse than is assumed by standard theories of
cerebellar function.
PMID- 28516454
TI - A multiscale computational modelling approach predicts mechanisms of female sex
risk in the setting of arousal-induced arrhythmias.
AB - KEY POINTS: This study represents a first step toward predicting mechanisms of
sex-based arrhythmias that may lead to important developments in risk
stratification and may inform future drug design and screening. We undertook
simulations to reveal the conditions (i.e. pacing, drugs, sympathetic
stimulation) required for triggering and sustaining reentrant arrhythmias. Using
the recently solved cryo-EM structure for the Eag-family channel as a template,
we revealed potential interactions of oestrogen with the pore loop hERG mutation
(G604S). Molecular models suggest that oestrogen and dofetilide blockade can
concur simultaneously in the hERG channel pore. ABSTRACT: Female sex is a risk
factor for inherited and acquired long-QT associated torsade de pointes (TdP)
arrhythmias, and sympathetic discharge is a major factor in triggering TdP in
female long-QT syndrome patients. We used a combined experimental and
computational approach to predict 'the perfect storm' of hormone concentration,
IKr block and sympathetic stimulation that induces arrhythmia in females with
inherited and acquired long-QT. More specifically, we developed mathematical
models of acquired and inherited long-QT syndrome in male and female ventricular
human myocytes by combining effects of a hormone and a hERG blocker, dofetilide,
or hERG mutations. These 'male' and 'female' model myocytes and tissues then were
used to predict how various sex-based differences underlie arrhythmia risk in the
setting of acute sympathetic nervous system discharge. The model predicted
increased risk for arrhythmia in females when acute sympathetic nervous system
discharge was applied in the settings of both inherited and acquired long-QT
syndrome. Females were predicted to have protection from arrhythmia induction
when progesterone is high. Males were protected by the presence of testosterone.
Structural modelling points towards two plausible and distinct mechanisms of
oestrogen action enhancing torsadogenic effects: oestradiol interaction with hERG
mutations in the pore loop containing G604 or with common TdP-related blockers in
the intra-cavity binding site. Our study presents findings that constitute the
first evidence linking structure to function mechanisms underlying female
dominance of arousal-induced arrhythmias.
PMID- 28516457
TI - Computed tomography or necropsy diagnosis of multiple bullae and the treatment of
pneumothorax in rhesus macaques (Macaca mulatta).
AB - Pulmonary bullae and pneumothorax have various etiologies in veterinary medicine.
We diagnosed multiple pulmonary bullae combined with or without pneumothorax by
computed tomography (CT) or necropsy in seven rhesus macaques (Macaca mulatta)
imported from China. Two of seven rhesus macaques accompanied by pneumothorax
were cured by fixation of ruptured lung through left or right 3rd intercostal
thoracotomy. Pneumonyssus simicola, one of the etiologies of pulmonary bullae,
was not detected from tracheobronchiolar lavage. To the best of our knowledge,
this is the first case report on the CT-aided diagnosis of pulmonary bullae and
the successful treatment of combined pneumothorax by thoracotomy in non-human
primates (NHPs).
PMID- 28516458
TI - YH12852, a potent and highly selective 5-HT4 receptor agonist, significantly
improves both upper and lower gastrointestinal motility in a guinea pig model of
postoperative ileus.
AB - BACKGROUND: Postoperative ileus (POI) is a transient gastrointestinal (GI)
dysmotility that commonly develops after abdominal surgery. YH12852, a novel,
potent and highly selective 5-hydroxytryptamine 4 (5-HT4 ) receptor agonist, has
been shown to improve both upper and lower GI motility in various animal studies
and may have applications for the treatment of POI. Here, we investigated the
effects and mechanism of action of YH12852 in a guinea pig model of POI to
explore its therapeutic potential. METHODS: The guinea pig model of POI was
created by laparotomy, evisceration, and gentle manipulation of the cecum for 60
seconds, followed by closure with sutures under anesthesia. Group 1 received an
oral administration of vehicle or YH12852 (1, 3, 10 or 30 mg/kg) only, while POI
Group 2 was intraperitoneally pretreated with vehicle or 5-HT4 receptor
antagonist GR113808 (10 mg/kg) prior to oral dosing of vehicle or YH12852 (3 or
10 mg/kg). Upper GI transit was evaluated by assessing the migration of a
charcoal mixture in the small intestine, while lower GI transit was assessed via
measurement of fecal pellet output (FPO). KEY RESULTS: YH12852 significantly
accelerated upper and lower GI transit at the doses of 3, 10, and 30 mg/kg and
reached its maximal effect at 10 mg/kg. These effects were significantly blocked
by pretreatment of GR113808 10 mg/kg. CONCLUSION AND INFERENCES: Oral
administration of YH12852 significantly accelerates and restores delayed upper
and lower GI transit in a guinea pig model of POI. This drug may serve as a
useful candidate for the treatment of postoperative ileus.
PMID- 28516460
TI - Taxane-Grafted Metal-Oxide Nanoparticles as a New Theranostic Tool against
Cancer: The Promising Example of Docetaxel-Functionalized Titanate Nanotubes on
Prostate Tumors.
AB - The combination of anticancer drugs and metal oxide nanoparticles is of great
interest in cancer nanomedicine. Here, the development of a new nanohybrid,
titanate nanotube-docetaxel (TiONts-DTX) is reported, the two parts of which are
conjugated by covalent linkages. Unlike most nanoparticles currently being
developed for biomedical purposes, TiONts present a needle-shaped morphology. The
surface of TiONts is linked with 3-aminopropyl triethoxysilane and with a hetero
bifunctional polymer (polyethylene glycol) to create well-dispersed and
biocompatible nanovectors. The prefunctionalized surface of this scaffold has
valuable attachments to graft therapeutic agents (DTX in our case) as well as
chelating agents (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) to
monitor the nanohybrids. To evaluate drug efficacy, in vitro tests have
demonstrated that the association between TiONts and DTX shows cytotoxic activity
against a hormone-refractory prostate cancer cell line (22Rv1) whereas TiONts
without DTX do not. Finally, the first in vivo tests with intratumoral injections
show that more than 70% of TiONts nanovectors are retained within the tumor for
at least 7 d. Moreover, tumor growth in mice receiving TiONts-DTX is
significantly slower than that in mice receiving free DTX. This nanohybrid can
thus become a promising new tool in biomedicine to fight against prostate cancer.
PMID- 28516461
TI - Effects of High-g Impact on Physical, Electrical, and Optical Characteristics of
Light-Emitting Diodes.
AB - Previously, one of the tools available in automotive or aircraft accident
analysis was the examination of the indicator bulbs. Currently, indicator bulbs
have been largely replaced by light-emitting diodes (LEDs). Here a series of
studies was carried out on impact effects on LEDs to determine whether their
properties change after impact, and whether it is related to its working status
(lit or unlit). The LEDs were measured before mechanical shock with a series of
tests, including current-voltage, current-light, bandwidth, subject to impact
ranging from 450 g to 2000 g, and then retested. The tests showed consistent
slight but statistically significant increases in forward voltages at a given
current after impact, which could be used to estimate the impact. Some LEDS were
imaged before and after impact with thermal and X-ray imaging, but no mechanical
changes were seen. It was not possible to determine the LED's working status from
these test results.
PMID- 28516459
TI - PP2A deactivation is a common event in oral cancer and reactivation by FTY720
shows promising therapeutic potential.
AB - Protein phosphatase 2A (PP2A) is a tumor suppressor gene, that has been
frequently deactivated in many types of cancer. However, its molecular and
clinical relevance in oral squamous cell carcinoma (OSCC) remain unclear. Here we
show that, PP2A deactivation is a common event in oral cancer cells and
hyperphosphorylation in its tyrosine-307 (Y307) residue contributes to PP2A
deactivation. PP2A restoration by FTY720 treatment reduced cell growth and
decreased GSK-3beta phosphorylation without significantly altering other PP2A
targets. We further detected PP2A phosphorylation in 262 OSCC tissues. Increased
expression of p-PP2A in the tumor tissues was significantly correlated with
higher N2/N3-stage (aOR = 2.1, 95%CI: 1.2-3.8). Patients with high p-PP2A
expression had lower overall survival rates than those with low expression.
Hazard ratio analysis showed that, high p-PP2A expression was significantly
associated with mortality density (aOR = 2.2, 95%CI: 1.2-4.0) and lower 10-year
overall survival (p = 0.027) in lymph node metastasis. However, no interaction
was observed between p-PP2A expression and lymph node metastasis. All our results
suggest that PP2A is frequently deactivated in oral cancer and determines poor
outcome, restoring its expression by FTY720 can be an alternative therapeutic
approach in OSCC.
PMID- 28516463
TI - Novel mutation of OCRL1 in Lowe syndrome with multiple epidermal cysts.
PMID- 28516462
TI - Metastatic right atrial hepatoma.
PMID- 28516464
TI - The Blood Donation Ambivalence Survey: measuring conflicting attitudes about
giving blood.
AB - OBJECTIVES: This study was designed to develop and conduct initial validation
testing for a novel measure of ambivalence about donating blood. BACKGROUND:
Previous studies of living organ, bone marrow and stem cell donors have
identified donation-related ambivalence as a predictor of decisions about
donation and post-donation outcomes. Ambivalence about blood donation has not
received the same attention. METHODS: In Study 1, a sample of young adults (N =
396) were administered test items of ambivalence, and exploratory (EFA) and
confirmatory factor analyses (CFA) were performed to identify the Blood Donation
Ambivalence Survey. In Study 2, a separate sample of young adults (N = 241)
completed the Blood Donation Ambivalence Survey in addition to questionnaires
assessing known predictors of blood donation. RESULTS: Exploratory and
confirmatory factor analyses indicated a two-factor structure reflecting
commitment to donating blood and indecision about giving blood. The commitment
subscale was positively related to known predictors of increased donation
behaviour (e.g. donation intention, self-efficacy), whereas the indecision
subscale was positively related to known predictors of decreased donation
behaviour (e.g. donation anxiety, negative affect). Furthermore, a history of
blood donation was associated with greater commitment and less indecision.
CONCLUSIONS: The present findings provide strong initial support for the
reliability and validity of a novel measure of blood donor ambivalence.
PMID- 28516465
TI - MAKINGtheLINK: A school-based intervention to improve help-seeking for substance
use problems.
AB - BACKGROUND: Many young people are reluctant to seek professional help for alcohol
and other substance use problems, preferring to rely on family and friends.
MAKINGtheLINK is a school-based intervention that teaches adolescents how to help
their peers overcome barriers to engaging with professional help. The current
study examined the effect of the MAKINGtheLINK programme in a sample of 12- to 15
year-old students. METHODS: Participants included 247 Grade 8 students (49% male,
51% female) recruited from 3 schools in Victoria, Australia. Participants
completed questionnaires measuring barriers to professional help-seeking, help
seeking intentions and confidence to seek help at 3 time points (pre
intervention, post-intervention and 6-week follow-up). A non-controlled repeated
measures design was used to assess the effect of the programme on help-seeking
across time points. RESULTS: The programme decreased barriers, increased
intentions to seek help from formal sources, decreased intentions to seek help
from family and increased confidence to seek help for a peer. The decrease in
barriers was maintained at the 6-week follow-up, as were decreased intentions to
seek help from family members, and increased intentions to seek help from school
counsellors and alcohol and drug workers. The effects of the intervention did not
differ substantially between males and females. CONCLUSIONS: The MAKINGtheLINK is
the first intervention to focus on overcoming barriers to help-seeking for
substance use problems by helping adolescents develop skills to support their
peers. The intervention has promise as a means of facilitating help-seeking
during adolescence, although further research is needed to test its effectiveness
in a more rigorous design.
PMID- 28516466
TI - Bioinspired Synthesis of Cu2+ -Modified Covalent Triazine Framework: A New Highly
Efficient and Promising Peroxidase Mimic.
AB - Artificial enzymes is an emerging field of research owing to the remarkable
advantages of enzyme mimics over their natural counterpart, including tunable
catalytic efficiencies, lower cost, ease of preparation, and excellent tolerance
to variations of the reaction system. Herein, we report an efficient peroxidase
mimic based on a copper-modified covalent triazine framework (CCTF). Owing to its
unique specific surface area, atomically dispersed active Cu sites, efficient
electron transfer, and enhanced photo-assisted enzyme-like activity, the CCTF
showed enhanced peroxidase-like enzyme activity. Therefore, copper modification
represents an effective route to tailor the peroxidase-like activity of the
covalent triazine frameworks. Furthermore, the mechanism of the enhanced
peroxidase-like activity and stability of the CCTF were investigated. As a proof
of concept, the CCTF was used for the colorimetric detection of H2 O2 and
decomposition of organic pollutants. This work provides a new strategy for the
design of enzyme mimics with a broad range of potential applications.
PMID- 28516467
TI - Lymph Vessel Thrombus Detection in Cervical Lymphedema: A Case Series.
AB - Although thrombosis in the terminal part of thoracic duct has been described in
patients with head and neck cancer and upper vein thrombosis, normally medical
imaging is not successful in depicting such lymphatic thrombosis. This case
series is about three patients with acute onset of cervical lymphedema following
minor trauma or exceptional physical strain. Using high-resolution ultrasound, it
was possible to detect a thrombus formation in the terminal parts of the thoracic
duct or the lymph duct. Within a few weeks all patients recovered without relapse
for several years.
PMID- 28516468
TI - Association between the frequency and autonomy of social participation and self
rated health.
AB - AIM: Although numerous studies have reported that social participation (SP) has
favorable effects on older people's health, no studies have focused on the
autonomy of SP. We investigated the cross-sectional relationship between the
type, frequency, and autonomy of SP and self-rated health (SRH). METHODS: A
postal survey was mailed to 19 354 citizens born between 1945 and 1949 in a city
in Nara prefecture (response rate: 65.9%). A total of 12 157 respondents (5114
men and 7043 women) with independent basic activities of daily living made up the
analytical participants. Six types of SP were measured: volunteer groups, sports
groups, hobby groups, senior citizens' clubs, neighborhood community associations
and cultural groups. Using multiple logistic regressions, we calculated the odds
ratio for poor SRH, with non-participation as the reference. Covariates included
age, family size, body mass index, comorbidities, smoking, drinking, walking,
depression and cognitive function. RESULTS: Adjusted odds ratios for poor SRH
decreased with more frequent SP or with more voluntary SP among both sexes, but
this dose-response relationship was stronger in women than in men. After mutual
adjustment for the frequency and autonomy of SP, voluntary SP had stronger
effects on SRH than frequent SP, especially in sports and hobby groups among men,
and in volunteer and hobby groups among women. For cultural groups, women with
frequent and voluntary SP had positive effects on SRH, but frequent and
obligatory SP had negative effects on men. CONCLUSIONS: The present results imply
that encouraging voluntarily chosen SP rather than frequent SP might be a key
point for successful aging. Geriatr Gerontol Int 2017; 17: 2537-2544.
PMID- 28516469
TI - Doxycycline as an anti-inflammatory agent: updates in dermatology.
AB - Doxycycline, a tetracycline antibiotic, is widely used in the field of
dermatology for its antibiotic properties, anti-inflammatory properties and good
safety profile. Over the past decades, numerous studies have clarified some of
the anti-inflammatory mechanisms of doxycycline. In this review article, we aimed
to provide an update on recent data on the anti-inflammatory properties of
doxycycline and its potential role in cutaneous inflammatory diseases. Better
understanding of these mechanisms might offer the practicing clinicians a better
use of this therapeutic tool. In addition, research in this field could help
clarify pathogenic aspects of inflammatory dermatologic diseases responsive to
this medication. Further research is needed to fully elucidate the potential of
doxycycline as an anti-inflammatory agent, and the development of new topical
vehicles could open ways to new therapeutic possibilities for dermatologists.
PMID- 28516470
TI - Survived so what? Identifying priorities for research with children and families
post-paediatric intensive care unit.
AB - The involvement of patients and the public in the development, implementation and
evaluation of health care services and research is recognized to have tangible
benefits in relation to effectiveness and credibility. However, despite >96% of
children and young people surviving critical illness or injury, there is a
paucity of published reports demonstrating their contribution to informing the
priorities for aftercare services and outcomes research. We aimed to identify the
service and research priorities for Paediatric Intensive Care Unit survivors with
children and young people, their families and other stakeholders. We conducted a
face-to-face, multiple-stakeholder consultation event, held in the Midlands (UK),
to provide opportunities for experiences, views and priorities to be elicited.
Data were gathered using write/draw and tell and focus group approaches. An
inductive content analytical approach was used to categorize and conceptualize
feedback. A total of 26 individuals attended the consultation exercise, including
children and young people who were critical care survivors; their siblings;
parents and carers; health professionals; academics; commissioners; and service
managers. Consultation findings indicated that future services, interventions and
research must be holistic and family-centred. Children and young people advisors
reported priorities that focused on longer-term outcomes, whereas adult advisors
identified priorities that mapped against the pathways of care. Specific
priorities included developing and testing interventions that address unmet
communication and information needs. Furthermore, initiatives to optimize the
lives and longer-term functional and psycho-social outcomes of Paediatric
Intensive Care Unit survivors were identified. This consultation exercise
provides further evidence of the value of meaningful patient and public
involvement in identifying the priorities for research and services for
Paediatric Intensive Care Unit survivors and illuminates differences in proposed
priorities between children, young people and adult advisors.
PMID- 28516471
TI - Topical non-steroidal anti-inflammatory drugs for analgesia in traumatic corneal
abrasions.
AB - BACKGROUND: Traumatic corneal abrasions are relatively common and there is a lack
of consensus about analgesia in their management. It is therefore important to
document the clinical efficacy and safety profile of topical ophthalmic non
steroidal anti-inflammatory drugs (NSAIDs) in the management of traumatic corneal
abrasions. OBJECTIVES: To identify and evaluate all randomised controlled trials
(RCTs) comparing the use of topical NSAIDs with placebo or any alternative
analgesic interventions in adults with traumatic corneal abrasions (including
corneal abrasions arising from foreign body removal), to reduce pain, and its
effects on healing time. SEARCH METHODS: We searched the Cochrane Central
Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and
Vision Trials Register) (2017, Issue 2), MEDLINE Ovid (1946 to 30 March 2017),
Embase Ovid (1947 to 30 March 2017), LILACS (Latin American and Caribbean Health
Sciences Literature Database) (1982 to 30 March 2017), OpenGrey (System for
Information on Grey Literature in Europe) (www.opengrey.eu/); searched 30 March
2017, ZETOC (1993 to 30 March 2017), the ISRCTN registry
(www.isrctn.com/editAdvancedSearch); searched 30 March 2017, ClinicalTrials.gov
(www.clinicaltrials.gov); searched 30 March 2017 and the WHO International
Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched
30 March 2017. We did not use any date or language restrictions in the electronic
searches for trials.We checked the reference lists of identified trials to search
for further potentially relevant studies. SELECTION CRITERIA: RCTs comparing
topical NSAIDs to placebo or any alternative analgesic interventions in adults
with traumatic corneal abrasions. DATA COLLECTION AND ANALYSIS: Two review
authors independently performed data extraction and assessed risks of bias in the
included studies. We rated the certainty of the evidence using GRADE. MAIN
RESULTS: We included nine studies that met the inclusion criteria, reporting data
on 637 participants.The studies took place in the UK, USA, Israel, Italy, France
and Portugal. These studies compared five types of topical NSAIDs (0.1%
indomethacin, 0.03% flurbiprofen, 0.5% ketorolac, 1% indomethacin, 0.1%
diclofenac) to control (consisting of standard care and in four studies used
placebo eye drops). Overall, the studies were at an unclear or high risk of bias
(particularly selection and reporting bias). None of the included studies
reported the primary outcome measures of this review, namely participant-reported
pain intensity reduction of 30% or more or 50% or more at 24 hours. Four trials,
that included data on 481 participants receiving NSAIDs or control
(placebo/standard care), reported on the use of 'rescue' analgesia at 24 hours as
a proxy measure of pain control. Topical NSAIDs were associated with a reduction
in the need for oral analgesia compared with control (risk ratio (RR) 0.46, 95%
confidence interval (CI) 0.34 to 0.61; low-certainty evidence). Approximately 4
out of 10 people in the control group used rescue analgesia at 24 hours. No data
were available on the use of analgesia at 48 or 72 hours.One trial (28
participants) reported on the proportion of abrasions healed after 24 and 48
hours. These outcomes were similar in both arms of the trial. (at 24 hours RR
1.00 (0.81 to 1.23); at 48 hours RR 1.00 (0.88 to 1.14); low-certainty evidence).
In the control group nine out of 10 abrasions were healed within 24 hours and all
were healed by 48 hours. Complications of corneal abrasions were reported in 6
studies (609 participants) and were infrequently reported (4 complications, 1 in
NSAID groups (recurrent corneal erosion) and 3 in control groups (2 recurrent
corneal erosions and 1 corneal abscess), very low-certainty evidence). Possible
drug-related adverse events (AEs) were reported in two trials (163 participants),
with the number of adverse events low (4 AEs, 3 in NSAID group, including
discomfort/photophobia on instillation, conjunctival hyperaemia and urticaria,
and 1 in the control group, corneal abscess) very low-certainty evidence.
AUTHORS' CONCLUSIONS: The findings of the included studies do not provide strong
evidence to support the use of topical NSAIDs in traumatic corneal abrasions.
This is important, since NSAIDs are associated with a higher cost compared to
oral analgesics. None of the trials addressed our primary outcome measure of
participant-reported pain intensity reduction of 30% or more or 50% or more at 24
hours.
PMID- 28516472
TI - Nasal decontamination for the prevention of surgical site infection in
Staphylococcus aureus carriers.
AB - BACKGROUND: Surgical site infection rates in the month following surgery vary
from 1% to 5%. Due to the large number of surgical procedures conducted annually,
the costs of these surgical site infections (SSIs) can be considerable in
financial and social terms. Nasal decontamination using antibiotics or
antiseptics is performed to reduce the risk of SSIs by preventing organisms from
the nasal cavity being transferred to the skin where a surgical incision will be
made. Staphylococcus aureus (S aureus) colonises the nasal cavity and skin of
carriers and can cause infection in open or unhealed surgical wounds. S aureus is
the leading nosocomial (hospital-acquired) pathogen in hospitals worldwide. The
potential effectiveness of nasal decontamination of S aureus is thought to be
dependent on both the antibiotic/antiseptic used and the dose of application;
however, it is unclear whether nasal decontamination actually reduces
postoperative wound infection in S aureus carriers. OBJECTIVES: To assess the
effects of nasal decontamination on preventing surgical site infections (SSIs) in
people who are S aureus carriers undergoing surgery. SEARCH METHODS: In September
2016 we searched the Cochrane Wounds Specialised Register, the Cochrane Central
Register of Controlled Trials (CENTRAL) (the Cochrane Library), Ovid MEDLINE,
Ovid MEDLINE (In-Process & Other Non-Indexed Citations), Ovid Embase, and EBSCO
CINAHL Plus. We also searched three clinical trial registries and the references
of included studies and relevant systematic reviews. There were no restrictions
based on language, date of publication or study setting. SELECTION CRITERIA:
Randomised controlled trials (RCTs) which enrolled S aureus carriers with any
type of surgery and assessed the use of nasal decontamination with
antiseptic/antibiotic properties were included in the review. DATA COLLECTION AND
ANALYSIS: Two review authors independently performed study selection, data
extraction, risk of bias assessment and GRADE assessment. MAIN RESULTS: We
located two studies (291 participants) for inclusion in this review. The trials
were clinically heterogeneous with differences in duration of follow-up, and
nasal decontamination regimens. One study compared mupirocin (2% contained in a
base of polyethylene glycol 400 and polyethylene glycol 3350) with a placebo in
elective cardiac surgery patients; and one study compared Anerdian (iodine 0.45%
to 0.57% (W/V), chlorhexidine acetate 0.09% to 0.11% (W/V)) with no treatment
also in cardiac surgery patients. The trials reported limited outcome data on
SSI, adverse events and secondary outcomes (e.g. S aureus SSI, mortality).
Mupirocin compared with placeboThis study found no clear difference in SSI risk
following use of mupirocin compared with placebo (1 trial, 257 participants);
risk ratio (RR) 1.60, 95% confidence interval (CI) 0.79 to 3.25 based on 18/130
events in the mupirocin group and 11/127 in the control group; low-certainty
evidence (downgraded twice due to imprecision). Anerdian compared with no
treatmentIt is uncertain whether there is a difference in SSI risk following
treatment with Anerdian compared with no treatment (1 trial, 34 participants); RR
0.89, 95% CI 0.06 to 13.08 based on 1/18 events in the Anerdian group and 1/16 in
the control group; very low certainty evidence (downgraded twice due to
imprecision and once due to risk of bias). AUTHORS' CONCLUSIONS: There is
currently limited rigorous RCT evidence available regarding the clinical
effectiveness of nasal decontamination in the prevention of SSI. This limitation
is specific to the focused question our review addresses, looking at nasal
decontamination as a single intervention in participants undergoing surgery who
are known S aureus carriers. We were only able to identify two studies that met
the inclusion criteria for this review and one of these was very small and poorly
reported. The potential benefits and harms of using decontamination for the
prevention of SSI in this group of people remain uncertain.
PMID- 28516473
TI - A ratiometric fluorescent chemosensor for the detection of cysteine in aqueous
solution at neutral pH.
AB - A ratiometric fluorescent chemosensor 2-(2'-hydroxy-3'-formyl-5'
methoxyphenyl)benzothiazole (1) was developed for the detection of cysteine
(Cys). In aqueous solution at neutral pH, 1 exhibited a ratiometric fluorescent
response to Cys with a remarkable red-to-green shift in the emission wavelength.
This fluorescence change was attributed to the cyclization reaction between the
formyl group in 1 and the amino and sulfhydryl group in Cys in a stoichiometry of
1: 1 according to the proposed mechanism. At neutral pH, 1 displayed a
significant fluorescence ratio signal enhancement with the addition of Cys.
Furthermore, 1 showed good selectivity toward Cys. The detection limit and linear
range were 5.6 and 0-100 MUmol/L, respectively, which demonstrated that 1 could
recognize relatively low concentrations of Cys and is a good candidate for
applications in detecting Cys.
PMID- 28516475
TI - Evaluation of detection distance-dependent reflectance spectroscopy for the
determination of the sun protection factor using pig ear skin.
AB - Determination of sun protection factors (SPFs) is currently an invasive method,
which is based on erythema formation (phototest). Here we describe an optical
setup and measurement methodology for the determination of SPFs based on diffuse
reflectance spectroscopy, which measures UV-reflectance spectra at 4 distances
from the point of illumination. Due to a high spatial variation of the
reflectance data, most likely due to inhomogeneities of the sunscreen
distribution, data of 50 measurement positions are averaged. A dependence of the
measured SPF on detection distance is significant for 3 sunscreens, while being
inconclusive for 2 sunscreens due to high inter-sample variations. Using pig ear
skin samples (n=6), the obtained SPF of 5 different commercial sunscreens
corresponds to the SPF values of certified test institutes in 3 cases and is
lower for 2 sunscreens of the same manufacturer, suggesting a formulation
specific reason for the discrepancy. The results demonstrate that the measurement
can be performed with a UV dose below the minimal erythema dose. We conclude the
method may be considered as a potential noninvasive in vivo alternative to the
invasive in vivo phototest, but further tests on different sunscreen formulations
are still necessary.
PMID- 28516476
TI - Massive retinal gliosis with episcleral extension.
PMID- 28516474
TI - Relationship between pain and motor and non-motor symptoms in Parkinson's
disease.
AB - BACKGROUND AND PURPOSE: Although female gender, depressive symptoms and medical
conditions predisposing to pain are more common in patients with Parkinson's
disease (PD) with pain, no study has yet explored the relationship between pain
and other non-motor symptoms (NMS). METHODS: A total of 321 consecutive patients
with PD [190 men/131 women aged 68.3 (SD 9.2) years] attending four Italian
movement disorder clinics were studied. Demographic/clinical data were obtained
by a standardized interview and the NMS scale. The association of pain with motor
and NMS was assessed by multivariable logistic regression models. RESULTS: At the
time of the study, 180 patients with PD (56%) reported chronic pain that, in most
cases, was described as being muscular or arthralgic pain. Pain preceded the
onset of motor signs in 36/180 patients. In the main-effect model, factors
independently associated with pain were female sex [odds ratio (OR), 2.1; P =
0.01], medical conditions predisposing to pain (OR, 2.9; P < 0.001), Hoehn-Yahr
staging (OR, 1.9; P = 0.04), motor complications (OR, 4.7; P = 0.04) and NMS
belonging to the sleep/fatigue (OR, 1.6; P = 0.04) and mood/cognition (OR, 1.6; P
= 0.03) domains. Most explanatory variables in the multivariable analysis were
similarly distributed in patients in whom pain may have been related to PD or to
a cause other than PD. CONCLUSIONS: We confirm that pain in PD is more frequent
in women and in subjects with medical conditions predisposing to painful
symptoms. Moreover, this strengthens the association between pain and motor
severity measures and NMS domains, particularly sleep and mood disturbances.
PMID- 28516477
TI - A prospective observational study on effects of fever on red cell transfusion
outcome.
AB - The effects of fever on red cell transfusions are not well documented. In this
pilot study, we have compared the outcome of red-blood-cell transfusions in
haematologic patients with and without fever. The results indicate that
haemoglobin increment per unit is significantly lower in febrile patients
receiving red cell transfusions than in patients without fever. These findings
are in line with earlier findings in preclinical studies. Larger studies are
necessary to confirm our results, and laboratory studies should be conducted to
investigate the underlying mechanisms.
PMID- 28516478
TI - Determination of oral bioavailability of curcuminoid dispersions and
nanoemulsions prepared from Curcuma longa Linnaeus.
AB - BACKGROUND: Curcuminoid from Curcuma longa Linnaeus has been demonstrated to be
effective in anti-cancer and anti-inflammation. The objectives of the present
study were to prepare curcuminoid dispersion and nanoemulsion from C. longa and
determine their oral bioavailabilities in rats. RESULTS: After curcuminoid
extraction using 99.5% ethanol, bisdemethoxycurcumin (BDMC), demethoxycurcumin
(DMC) and curcumin were separated within 10 min by high-performance liquid
chromatography using an Eclipse XDB-C18 column (Agilent, Palo Alto, CA, USA) and
a gradient mobile phase of 0.1% aqueous formic acid and acetonitrile, with a flow
rate of 1 mL min-1 , column temperature of 35 degrees C and detection wavelength
of 425 nm. Curcuminoid nanoemulsion at a particle size of 12.1 nm and
encapsulation efficiency 98.8% was prepared using lecithin, Tween 80 and water. A
pharmacokinetic study in rats revealed that the parameters including Tmax , Cmax
, t1/2 and the area under the curve were higher for curcuminoid nanoemulsions
than for curcuminoid dispersion at the same dose employed for gavage
administration, whereas, for intravenous injection, an opposite trend was shown.
The oral bioavailabilities of BDMC, DMC, curcumin and total curcuminoids in
nanoemulsion and dispersion were 34.39 and 4.65%, 39.93 and 5.49%, 47.82 and
9.38%, and 46 and 8.7%, respectively. CONCLUSION: The results of the present
study demonstrate a higher oral bioavailability after incorporation of
curcuminoid into nanoemulsion, facilitating its application as a botanic drug.
(c) 2017 Society of Chemical Industry.
PMID- 28516480
TI - Development and feasibility of smartphone application for cognitive-behavioural
case management of individuals with early psychosis.
AB - BACKGROUND: This article describes the development of the smartphone application
for cognitive-behavioural case management of young individuals with early
psychosis and examines the acceptance and potential clinical benefits of this
application through a pilot survey. METHODS: Gwangju Bukgu-Community Mental
Health Center developed and launched a smartphone application (Heal Your Mind
[HYM]) for cognitive-behavioural case management and symptom monitoring. The HYM
application for clients includes 6 main modules including thought record, symptom
record, daily life record, official notices, communication and scales. The key
module is the "thought record" for self-directed cognitive-behavioural treatment.
When the client writes and sends the self-cognitive-behavioural therapy sheet to
the case manager, the latter receives a notification and can provide feedback in
real time. We conducted a survey to investigate the acceptance and feasibility of
this approach among young clients with early psychosis. RESULTS: A total of 24
clients with early psychosis participated in this survey. More than 80% of
participants reported that it was easy to learn to use this application, and no
one described this application as very complicated or reported that they needed a
long time to learn how to use it. About 80% of participants were satisfied with
this application, and 70% reported that they received help as a result of using
this application. CONCLUSIONS: This study suggests that this smartphone
application is useful for young individuals with early psychosis and that it may
contribute to the development of both young customer- and case manager-friendly
systems for this clinical population.
PMID- 28516481
TI - Massive mediastinal enlargement due to extramedullary haematopoiesis in a patient
with MYH9-related thrombocytopenia.
PMID- 28516482
TI - Multiple boli arterial spin labeling for high signal-to-noise rodent brain
perfusion imaging.
AB - PURPOSE: A systematic method is proposed for optimizing a promising preclinical
arterial spin labeling (ASL) sequence based on the use of a train of adiabatic
radiofrequency pulses labeling successive boli of blood water. METHODS: The
sequence optimization is performed and evaluated using brain imaging experiments
in mice and in rats. It involves the investigation of several parameters, ranging
from the number of adiabatic pulses and labeling duration to the properties of
the adiabatic hyperbolic secant pulses (ie, amplitude and frequency modulation).
RESULTS: Species-dependent parameters are identified, allowing for robust fast
optimization protocols to be introduced. The resulting optimized multiple boli
ASL (mbASL) sequence provides with significantly higher average signal-to-noise
ratios (SNR) per voxel volume than currently encountered in ASL studies (278 mm-3
in mice and 172 mm-3 in rats). Comparing with the commonly used flow-sensitive
alternating inversion recovery technique (FAIR), mbASL-to-FAIR SNR ratios reach
203% for mice and 725% for rats. CONCLUSION: When properly optimized, mbASL can
offer a robust, high SNR ASL alternative for rodent brain perfusion studies Magn
Reson Med 79:1020-1030, 2018. (c) 2017 International Society for Magnetic
Resonance in Medicine.
PMID- 28516479
TI - Galphas signalling of the CB1 receptor and the influence of receptor number.
AB - BACKGROUND AND PURPOSE: CB1 receptor signalling is canonically mediated through
inhibitory Galphai proteins, but occurs through other G proteins under some
circumstances, Galphas being the most characterized secondary pathway.
Determinants of this signalling switch identified to date include Galphai
blockade, CB1 /D2 receptor co-stimulation, CB1 agonist class and cell background.
Hence, we examined the effects of receptor number and different ligands on CB1
receptor signalling. EXPERIMENTAL APPROACH: CB1 receptors were expressed in HEK
cells at different levels, and signalling characterized for cAMP by real-time
BRET biosensor -CAMYEL - and for phospho-ERK by AlphaScreen. Homogenate and whole
cell radioligand binding assays were performed to characterize AM6544, a novel
irreversible CB1 receptor antagonist. KEY RESULTS: In HEK cells expressing high
levels of CB1 receptors, agonist treatment stimulated cAMP, a response not known
to be mediated by receptor number. Delta9 -THC and BAY59-3074 increased cAMP only
in high-expressing cells pretreated with pertussis toxin, and agonists
demonstrated more diverse signalling profiles in the stimulatory pathway than the
canonical inhibitory pathway. Pharmacological CB1 receptor knockdown and Galphai
1 supplementation restored canonical Galphai signalling to high-expressing cells.
Constitutive signalling in both low- and high-expressing cells was Galphai
mediated. CONCLUSION AND IMPLICATIONS: CB1 receptor coupling to opposing G
proteins is determined by both receptor and G protein expression levels, which
underpins a mechanism for non-canonical signalling in a fashion consistent with
Galphas signalling. CB1 receptors mediate opposite consequences in endpoints such
as tumour viability depending on expression levels; our results may help to
explain such effects at the level of G protein coupling.
PMID- 28516484
TI - Incidental finding of recent parvovirus infection.
PMID- 28516483
TI - Capabilities and limitations of DGGE for the analysis of hydrocarbonoclastic
prokaryotic communities directly in environmental samples.
AB - Prokaryotic communities in pristine and oil-contaminated desert soil, seawater,
and hypersaline coastal soil were analyzed using culture-dependent and culture
independent approaches. The former technique was the dilution-plating method. For
the latter, total genomic DNA was extracted and the 16S rRNA genes were amplified
using a universal bacterial primer pair and primer pairs specific for
Actinobacteria, Gammaproteobacteria, and Archaea. The amplicons were resolved
using denaturing gradient gel electrophoresis (DGGE) and sequenced, and the
sequences were compared to those in GenBank. The plating method offered the
advantages of capturing the targeted hydrocarbonoclastic microorganisms, counting
them and providing cultures for further study. However, this technique could not
capture more than a total of 15 different prokaryotic taxa. Those taxa belonged
predominantly to the genera Alcanivorax, Pseudoxanthomonas, Bosea, Halomonas, and
Marinobacter. The individual isolates in culture consumed between 19 and 50% of
the available crude oil in 10 days. Although the culture-independent approach
revealed much more microbial diversity, it was not problem-free. The subdivision
primers exhibited satisfactory specificity, but they failed to capture all the
available taxa. The universal bacterial primer pair ignored Actinobacteria
altogether, although the primer pair specific for Actinobacteria captured many of
them, for example, the genera Geodermatophilus, Streptomyces, Mycobacterium,
Pontimonas, Rhodococcus, Blastococcus, Kocuria, and many others. Because most
researchers worldwide use universal primers for PCR, this finding should be
considered critically to avoid misleading interpretations.
PMID- 28516488
TI - Aged care nurses' job control influence satisfaction and mental health.
AB - BACKGROUND: Relationships exist between aged care nurses' perceptions of
psychosocial work characteristics, job satisfaction and mental health, suggesting
these characteristics may be important for the management of aged care services.
AIM: An expanded demand-control-support model that included justice perceptions
was examined to determine its impact on multiple types of psychological and
organisational well-being outcomes (i.e. job satisfaction, psychological distress
and depression). METHOD: Data were collected from a sample of 173 aged care
nurses using a self-report survey and analysed using hierarchical multiple
regression. RESULTS: A significant proportion (27-28%) of the variance in aged
care nurses' satisfaction, depression and psychological distress was explained by
the psychosocial factors included in the model. Job control had the most
consistent impact with direct effects on job satisfaction, psychological distress
and depression. Informational justice was associated with both psychological
distress and depression. CONCLUSIONS: Targeting job control may provide the
biggest response for nurse managers in aged care, as it is likely to influence
nurses' job satisfaction, psychological distress and depression. IMPLICATIONS FOR
NURSING MANAGEMENT: Facility managers should implement organisational policies
and procedures that promote higher levels of control over how nurses perform
their work in order to improve nurse well-being in aged care settings.
PMID- 28516485
TI - Simultaneous measurement of T2 and apparent diffusion coefficient (T2 +ADC) in
the heart with motion-compensated spin echo diffusion-weighted imaging.
AB - PURPOSE: To evaluate a technique for simultaneous quantitative T2 and apparent
diffusion coefficient (ADC) mapping in the heart (T2 +ADC) using spin echo (SE)
diffusion-weighted imaging (DWI). THEORY AND METHODS: T2 maps from T2 +ADC were
compared with single-echo SE in phantoms and with T2 -prepared (T2 -prep)
balanced steady-state free precession (bSSFP) in healthy volunteers. ADC maps
from T2 +ADC were compared with conventional DWI in phantoms and in vivo. T2 +ADC
was also demonstrated in a patient with acute myocardial infarction (MI).
RESULTS: Phantom T2 values from T2 +ADC were closer to a single-echo SE reference
than T2 -prep bSSFP (-2.3 +/- 6.0% vs 22.2 +/- 16.3%; P < 0.01), and ADC values
were in excellent agreement with DWI (0.28 +/- 0.4%). In volunteers, myocardial
T2 values from T2 +ADC were significantly shorter than T2 -prep bSSFP (35.8 +/-
3.1 vs 46.8 +/- 3.8 ms; P < 0.01); myocardial ADC was not significantly (N.S.)
different between T2 +ADC and conventional motion-compensated DWI (1.39 +/- 0.18
vs 1.38 +/- 0.18 mm2 /ms; P = N.S.). In the patient, T2 and ADC were both
significantly elevated in the infarct compared with remote myocardium (T2 : 40.4
+/- 7.6 vs 56.8 +/- 22.0; P < 0.01; ADC: 1.47 +/- 0.59 vs 1.65 +/- 0.65 mm2 /ms;
P < 0.01). CONCLUSION: T2 +ADC generated coregistered, free-breathing T2 and ADC
maps in healthy volunteers and a patient with acute MI with no cost in accuracy,
precision, or scan time compared with DWI. Magn Reson Med 79:654-662, 2018. (c)
2017 International Society for Magnetic Resonance in Medicine.
PMID- 28516487
TI - The petrosal and bony labyrinth of Diplobune minor, an enigmatic Artiodactyla
from the Oligocene of Western Europe.
AB - Anoplotheriinae are Paleogene European artiodactyls that present a unique
postcranial morphology with a tridactyl autopodium and uncommon limb orientation.
This peculiar morphology led to various hypotheses regarding anoplotheriine
locomotion from semiaquatic to partly arboreal or partly bipedal. The petrosal
bone, housing the organs of balance, and hearing, offers complementary
information to postcranial morphology on the ecology of this uncommon
artiodactyl. Here, we investigate the middle ear and bony labyrinth of the small
anoplotheriine Diplobune minor based on four specimens from the Early Oligocene
locality of Itardies (Quercy, France). A macroscopic study coupled with a MUCT
scan investigation of the petrosal anatomy provides novel information on the bony
labyrinth, stapes, and innervation and vasculature of the inner ear of this
enigmatic taxon. The petrosal of D. minor exhibits a mosaic of plesiomorphic
characters and peculiar features that shed new light into the anatomy of this
poorly studied taxon of an obscure taxonomic clade. We can confidently reject
that D. minor was a semiaquatic species based on the petrosal morphology:
presence of a large mastoid process and nonpachyostotic tegmen tympani do not
support underwater hearing. On the other hand, the average semicircular canal
radius points to a slow or medium slow agility for D. minor, and fully rejects it
was a fast moving animal, which is congruent with its postcranial anatomy.
PMID- 28516489
TI - Comment on "Three-dimensional ultrasonographic depiction of fetal brain blood
vessels".
PMID- 28516490
TI - Termination of pregnancy due to renal tract abnormalities: survey of 97 fetuses
from a single medical center.
PMID- 28516491
TI - Letter to the Editor: Professional nursing introductions: key to
interprofessional collaboration.
PMID- 28516492
TI - Telemedicine in dermatology: findings and experiences worldwide - a systematic
literature review.
AB - Telemedicine has become an important element of health care in many countries and
profited from the technological progress of the last two decades. Due to the
visual character of the dermatological specialty, teledermatology in particular
participated in that development and is becoming a major tool in dermatological
consultation. The objective of this article was to identify the use of
teledermatology across the world based on published original articles. A
systematic literature search of the MEDLINE and Embase databases for eligible
publications (predefined inclusion and exclusion criteria) and a cross-validation
search were conducted. Search results were reviewed systematically. The search
resulted in 204 publications meeting the inclusion criteria for analysis. The
highest number of published studies on teledermatology was performed in the
United States, followed by the United Kingdom, Spain, the Netherlands, Italy and
Austria. The majority of dermatological indications for telemedical consultations
were not specified or included various kinds of skin diseases, followed by skin
cancer and wounds. Research questions predominantly focused on concordance,
effectiveness and cost-effectiveness to determine the value. Teledermatology
proved to be a reliable consultation tool in the majority of studies. If
specified, telemedicine was used in daily dermatological routine for patient
management purposes, to consult patients in peripheral locations, or for medical
support in nursing homes or home care settings. The application of
teledermatology worldwide is highest in North American and European countries,
while countries with poor geographical distribution of physicians seem to be
under-represented in teledermatological use, as concluded from publication
output. Regarding indications, comparison with classic consultation and area of
application, most studies were of general nature. For precise determination of
the value, systematic studies would be needed. However, teledermatology is
already accepted as a valid tool.
PMID- 28516493
TI - Diagnosis and treatment of dermatophytosis in dogs and cats.: Clinical Consensus
Guidelines of the World Association for Veterinary Dermatology.
AB - BACKGROUND: Dermatophytosis is a superficial fungal skin disease of cats and
dogs. The most common pathogens of small animals belong to the genera Microsporum
and Trichophyton. It is an important skin disease because it is contagious,
infectious and can be transmitted to people. OBJECTIVES: The objective of this
document is to review the existing literature and provide consensus
recommendations for veterinary clinicians and lay people on the diagnosis and
treatment of dermatophytosis in cats and dogs. METHODS: The authors served as a
Guideline Panel (GP) and reviewed the literature available prior to September
2016. The GP prepared a detailed literature review and made recommendations on
selected topics. The World Association of Veterinary Dermatology (WAVD) provided
guidance and oversight for this process. A draft of the document was presented at
the 8th World Congress of Veterinary Dermatology (May 2016) and was then made
available via the World Wide Web to the member organizations of the WAVD for a
period of three months. Comments were solicited and posted to the GP
electronically. Responses were incorporated by the GP into the final document.
CONCLUSIONS: No one diagnostic test was identified as the gold standard.
Successful treatment requires concurrent use of systemic oral antifungals and
topical disinfection of the hair coat. Wood's lamp and direct examinations have
good positive and negative predictability, systemic antifungal drugs have a wide
margin of safety and physical cleaning is most important for decontamination of
the exposed environments. Finally, serious complications of animal-human
transmission are exceedingly rare.
PMID- 28516494
TI - Recommendations for approaches to meticillin-resistant staphylococcal infections
of small animals: diagnosis, therapeutic considerations and preventative
measures.: Clinical Consensus Guidelines of the World Association for Veterinary
Dermatology.
AB - BACKGROUND: Multiple drug resistance (MDR) in staphylococci, including resistance
to the semi-synthetic penicillinase-resistant penicillins such as meticillin, is
a problem of global proportions that presents serious challenges to the
successful treatment of staphylococcal infections of companion animals.
OBJECTIVES: The objective of this document is to provide harmonized
recommendations for the diagnosis, prevention and treatment of meticillin
resistant staphylococcal infections in dogs and cats. METHODS: The authors served
as a Guideline Panel (GP) and reviewed the literature available prior to
September 2016. The GP prepared a detailed literature review and made
recommendations on selected topics. The World Association of Veterinary
Dermatology (WAVD) provided guidance and oversight for this process. A draft of
the document was presented at the 8th World Congress of Veterinary Dermatology
(May 2016) and was then made available via the World Wide Web to the member
organizations of the WAVD for a period of three months. Comments were solicited
and posted to the GP electronically. Responses were incorporated by the GP into
the final document. CONCLUSIONS: Adherence to guidelines for the diagnosis,
laboratory reporting, judicious therapy (including restriction of use policies
for certain antimicrobial drugs), personal hygiene, and environmental cleaning
and disinfection may help to mitigate the progressive development and
dissemination of MDR staphylococci.
PMID- 28516495
TI - Introduction to the World Association for Veterinary Dermatology and the Clinical
Consensus Guidelines.
PMID- 28516496
TI - The Impact of Childhood Obesity on Health and Health Service Use.
AB - OBJECTIVE: To test the impact of obesity on health and health care use in
children, by the use of various methods to account for reverse causality and
omitted variables. DATA SOURCES/STUDY SETTING: Fifteen rounds of the Health
Survey for England (1998-2013), which is representative of children and
adolescents in England. STUDY DESIGN: We use three methods to account for reverse
causality and omitted variables in the relationship between BMI and health/health
service use: regression with individual, parent, and household control variables;
sibling fixed effects; and instrumental variables based on genetic variation in
weight. DATA COLLECTION/EXTRACTION METHODS: We include all children and
adolescents aged 4-18 years old. PRINCIPAL FINDINGS: We find that obesity has a
statistically significant and negative impact on self-rated health and a positive
impact on health service use in girls, boys, younger children (aged 4-12), and
adolescents (aged 13-18). The findings are comparable in each model in both boys
and girls. CONCLUSIONS: Using econometric methods, we have mitigated several
confounding factors affecting the impact of obesity in childhood on health and
health service use. Our findings suggest that obesity has severe consequences for
health and health service use even among children.
PMID- 28516497
TI - Total Synthesis of O-GalNAcylated Antifreeze Glycoprotein using the Switchable
Reactivity of Peptidyl-N-pivaloylguanidine.
AB - Antifreeze glycoprotein (AFGP) is an O-glycoprotein that displays antifreeze
activity through depression of the freezing point of water. GalNAc is a core
sugar structure of AFGP, and contributes to induce antifreeze activity of this
glycoprotein. However, the general functional role that this sugar plays at the
molecular level is still unknown. To elucidate this, it is essential to determine
the relationship between structure and activity of O-GalNAcylated AFGP using
homogeneous glycoproteins. Thus, the total synthesis of homogeneous O
GalNAcylated AFGP was conducted by using a unique peptide derivative: peptidyl-N
pivaloylguanidine. It was found that peptidyl-N-pivaloylguanidine is an
"unreactive" peptide in peptide coupling reactions but is interconvertible with a
"reactive" peptide-alpha-thioester by means of a simple treatment under buffer
condition at pH=7 to 8. The unique switchable reactivity of peptidyl-N
pivaloylguanidine enabled an efficient sequential peptide coupling strategy. By
using this strategy, various lengths of homogeneous O-GalNAcylated AFGP were
synthesized, including one that was 120 amino acids in length, with 40 O
GalNAcylation sites. The structural analysis by circular dichroism spectroscopy
and evaluation of the antifreeze activity of the synthetic AFGP(GalNAc)s revealed
that the simple O-glycosylation with GalNAc is essential for both structural and
functional basis of AFGP to exhibit antifreeze activity.
PMID- 28516498
TI - Non-parallel divergence across freshwater and marine three-spined stickleback
Gasterosteus aculeatus populations.
AB - This work investigated whether multiple freshwater populations of three-spined
stickleback Gasterosteus aculeatus in different freshwater catchments in the
Jutland Peninsula, Denmark, derived from the same marine populations show
repeated adaptive responses. A total of 327 G. aculeatus collected at 13 sampling
locations were screened for genetic variation using a combination of 70 genes
putatively under selection and 26 neutral genes along with a marker linked to the
ectodysplasin gene (eda), which is strongly correlated with plate armour morphs
in the species. A highly significant genetic differentiation was found that was
higher among different freshwater samples than between marine-freshwater samples.
Tests for selection between marine and freshwater populations showed a very low
degree of parallelism and no single nucleotide polymorphism was detected as
outlier in all freshwater-marine pairwise comparisons, including the eda. This
suggests that G. aculeatus is not necessarily the prime example of parallel local
adaptation suggested in much of the literature and that important exceptions
exist (i.e. the Jutland Peninsula). While marine populations in the results
described here showed a high phenotype-genotype correlation at eda, a low
association was found for most of the freshwater populations. The most extreme
case was found in the freshwater Lake Hald where all low-plated phenotypes were
either homozygotes for the allele supposed to be associated with completely
plated morphs or heterozygotes, but none were homozygotes for the putative low
plated allele. Re-examination of data from seven G. aculeatus studies agrees in
showing a high but partial association between phenotype-genotype at eda in G.
aculeatus freshwater populations and that mismatches occur everywhere in the
European regions studied (higher in some areas, i.e. Denmark). This is
independent of the eda marker used.
PMID- 28516499
TI - Spectrofluorometric determination of clonazepam in dosage forms: Application to
content uniformity testing and human plasma.
AB - The present paper describes a developed and validated simple, highly sensitive
and cost-effective spectrofluorometric method for determination of clonazepam
(CNP). The proposed method depends on forming a highly fluorescent product
through the reduction of CNP with Zn/HCl. The produced fluorophore exhibits a
strong fluorescence at lambdaem 350 nm after excitation at lambdaex 250 nm. The
use of carboxymethylcellulose (CMC) greatly enhanced the fluorescence intensity
of the produced fluorophore to the extent of about 100%. Calibration curve showed
good linear regression (r2 > 0.9998) within test ranges of 20-400 ng ml-1 with a
lower detection limit of 0.67 ng ml-1 and lower quantification limit of 2.22 ng
ml-1 upon using CMC. The method was successfully applied to the analysis of CNP
in its pharmaceutical formulations and the results were in agreement with those
obtained using a reference method. Furthermore, the content uniformity testing of
the tablets was also performed. The application of the proposed method was
extended to determine CNP in spiked human plasma sample as a preliminary
investigation and the results were satisfactory.
PMID- 28516500
TI - Healthcare utilisation, induced labour and caesarean section in the pregnancy
after stillbirth: a prospective study.
AB - OBJECTIVE: To investigate healthcare utilisation, induced labour and caesarean
section (CS) in the pregnancy after stillbirth and assess anxiety and dread of
childbirth as mediators for these outcomes. DESIGN: Population-based pregnancy
cohort study. SETTING: The Norwegian Mother and Child Cohort Study. SAMPLE: A
total of 901 pregnant women; 174 pregnant after stillbirth, 362 pregnant after
live birth and 365 previously nulliparous. METHODS: Data from questionnaires
answered in the second and third trimesters of pregnancy and information from the
Medical Birth Registry of Norway. MAIN OUTCOME MEASURES: Self-reported assessment
of antenatal care, register-based assessment of onset and mode of delivery.
RESULTS: Women with a previous stillbirth had more frequent antenatal visits
(mean 10.0; 95% CI 9.4-10.7) compared with women with a previous live birth (mean
6.0; 95% CI 5.8-6.2) and previously nulliparous women (mean 6.3; 95% CI 6.1-6.6).
Induced labour and CS, elective and emergency, were also more prevalent in the
stillbirth group. The adjusted odds ratio for elective CS was 2.5 (95% CI 1.3
5.0) compared with women with previous live birth and 3.7 (1.8-7.6) compared with
previously nulliparous women. Anxiety was a minor mediator for the association
between stillbirth and frequency of antenatal visits, whereas dread of childbirth
was not a significant mediator for elective CS. CONCLUSIONS: Women pregnant after
stillbirth were more ample users of healthcare services and more often had
induced labour and CS. The higher frequency of antenatal visits and elective CS
could not be accounted for by anxiety or dread of childbirth. TWEETABLE ABSTRACT:
Women pregnant after stillbirth are ample users of healthcare services and
interventions during childbirth.
PMID- 28516501
TI - The histone acetyltranseferase KAT8 regulates cell differentiation by suppression
of MN1 in AML.
PMID- 28516502
TI - Differential effects of exposure to parasites and bacteria on stress response in
turbot Scophthalmus maximus simultaneously stressed by low water depth.
AB - The stress response of turbot Scophthalmus maximus was evaluated in fish
maintained 8 days under different water depths, normal (NWD, 30 cm depth, total
water volume 40 l) or low (LWD, 5 cm depth, total water volume 10 l), in the
additional presence of infection-infestation of two pathogens of this species.
This was caused by intraperitoneal injection of sublethal doses of the bacterium
Aeromonas salmonicida subsp. salmonicida or the parasite Philasterides
dicentrarchi (Ciliophora:Scuticociliatida). The LWD conditions were stressful for
fish, causing increased levels of cortisol in plasma, decreased levels of
glycogen in liver and nicotinamide adenine dinucleotide phosphate (NADP) and
increased activities of G6Pase and GSase. The presence of bacteria or parasites
in fish under NWD resulted in increased cortisol levels in plasma whereas in
liver, changes were of minor importance including decreased levels of lactate and
GSase activity. The simultaneous presence of bacteria and parasites in fish under
NWD resulted a sharp increase in the levels of cortisol in plasma and decreased
levels of glucose. Decreased levels of glycogen and lactate and activities of
GSase and glutathione reductase (GR), as well as increased activities of glucose
6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH) and
levels of nicotinamide adenine dinucleotide phosphate (NADPH) occurred in the
same fish in liver. Finally, the presence of pathogens in S. maximus under
stressful conditions elicited by LWD resulted in synergistic actions of both type
of stressors in cortisol levels. In liver, the presence of bacteria or parasites
induced a synergistic action on several variables such as decreased activities of
G6Pase and GSase as well as increased levels of NADP and NADPH and increased
activities of GPase, G6PDH and 6PGDH.
PMID- 28516503
TI - Sonovaginography: A Useful Technique in the Assessment of the Lower Genital
Tract.
AB - Conventional sonographic evaluation of the cervix and vagina is compromised by
inattention, poor subject contrast, and obscuring artifacts. We describe a
technique involving distention of the vaginal canal and fornices with ultrasound
gel, providing an acoustic window for improved definition of the cervix and
vagina. This exam is usually performed in concert with transvaginal sonography,
but a transabdominal or transperineal approach may be more useful in selected
scenarios. A wide variety of formerly sonographically inconspicuous conditions
are demonstrable with this technique, many of which were undetected or
inadequately characterized on the physical exam. Cervical polyps were the most
commonly seen abnormality.
PMID- 28516504
TI - Prognostic potential of midregional pro-adrenomedullin following decompensation
for systolic heart failure: comparison with cardiac natriuretic peptides.
AB - AIMS: Whereas guidelines recommend the routine use of natriuretic peptides (NPs)
in heart failure (HF) care, the clinical relevance and prognostic potential of
midregional pro-adrenomedullin (MR-proADM) is less well established. We aimed to
compare the prognostic potential of MR-proADM after acute decompensation for
systolic HF with that of N-terminal pro-B-type natriuretic peptide (NT-proBNP)
and midregional pro-atrial NP (MR-proANP), to investigate the significance of
high/rising MR-proADM, and to evaluate the incremental prognostic yield of repeat
measurements. METHODS AND RESULTS: The Interdisciplinary Network Heart Failure
(INH) programme enrolled patients hospitalized for acute systolic HF and followed
them for 18 months (100% complete). Of 1022 INH participants, 917 (68 +/- 12
years, 28% female) who had biomaterials available were enrolled. High MR-proADM
was associated with more impaired left ventricular function, higher comorbidity
burden, lower doses of HF medications, and lower likelihood of left ventricular
reverse remodelling. Compared with NPs, MR-proADM had superior prognostic
significance (concordance index 0.72 for all-cause mortality), improved Cox
regression models including NPs (P < 0.001), and was the only biomarker also
predicting non-cardiac death (hazard ratio 1.8 vs. 1.0). In the setting of low
NPs, patients with high MR-proADM experienced non-cardiac death more often. Six
month MR-proADM enhanced models including baseline MR-proADM (P < 0.001) for
prediction of all-cause death (net reclassification index: 0.48, 95% confidence
interval 0.19-0.78). CONCLUSION: MR-proADM was found to correlate with the global
disease burden in HF and proved a potent prognostic indicator, capturing the risk
for both cardiac and non-cardiac death. Serial MR-proADM measurements further
enhanced risk assessment, thus facilitating substantial reclassification.
PMID- 28516505
TI - Associations between nursing home performance and hospital 30-day readmissions
for acute myocardial infarction, heart failure and pneumonia at the healthcare
community level in the United States.
AB - OBJECTIVES: To evaluate community-specific nursing home performance with
community-specific hospital 30-day readmissions for Medicare patients discharged
with acute myocardial infarction, heart failure or pneumonia. DESIGN: Cross
sectional study using 2009-2012 hospital risk-standardised 30-day readmission
data for Medicare fee-for-service patients hospitalised for all three conditions
and nursing home performance data from the Centers for Medicare & Medicaid
Services Five-Star Quality Rating System. SETTING: Medicare-certified nursing
homes and acute care hospitals. PARTICIPANTS: 12,542 nursing homes and 3,039
hospitals treating 30 or more Medicare fee-for-service patients for all three
conditions across 2,032 hospital service areas in the United States.
MEASUREMENTS: Community-specific hospital 30-day risk-standardised readmission
rates. Community-specific nursing home performance measures: health inspection,
staffing, Registered Nurses and quality performance; and an aggregated
performance score. Mixed-effects models evaluated associations between nursing
home performance and hospital 30-day risk-standardised readmission rates for all
three conditions. RESULTS: The relationship between community-specific hospital
risk-standardised readmission rates and community-specific overall nursing home
performance was statistically significant for all three conditions. Increasing
nursing home performance by one star resulted in decreases of 0.29% point (95%
CI: 0.12-0.47), 0.78% point (95% CI: 0.60-0.95) and 0.46% point (95% CI: 0.33
0.59) of risk-standardised readmission rates for AMI, HF and pneumonia,
respectively. Among the specific measures, higher performance in nursing home
overall staffing and Registered Nurse staffing measures was statistically
significantly associated with lower hospital readmission rates for all three
conditions. Notable geographic variation in the community-specific nursing home
performance was observed. CONCLUSION: Community-specific nursing home performance
is associated with community-specific hospital 30-day readmission rates for
Medicare fee-for-service patients for acute myocardial infarction, heart failure
or pneumonia. IMPLICATIONS FOR PRACTICE: Coordinated care between hospitals and
nursing homes is essential to reduce readmissions. Nursing homes can improve
performance and reduce readmissions by increasing registered nursing homes.
Further, communities can work together to create cross-continuum care teams
comprised of hospitals, nursing homes, patients and their families, and other
community-based service providers to reduce unplanned readmissions.
PMID- 28516506
TI - Diversity of Chemical Bonding and Oxidation States in MS4 Molecules of Group 8
Elements.
AB - The geometric and electronic ground-state structures of 30 isomers of six MS4
molecules (M=Group 8 metals Fe, Ru, Os, Hs, Sm, and Pu) have been studied by
using quantum-chemical density functional theory and correlated wavefunction
approaches. The MS4 species were compared to analogous MO4 species recently
investigated (W. Huang, W.-H. Xu, W. H. E. Schwarz, J. Li, Inorg. Chem. 2016, 55,
4616). A metal oxidation state (MOS) with a high value of eight appeared in the
low-spin singlet Td geometric species (Os,Hs)S4 and (Ru,Os,Hs)O4 , whereas a low
MOS of two appeared in the high-spin septet D2d species Fe(S2 )2 and (slightly
excited) metastable Fe(O2 )2 . The ground states of all other molecules had
intermediate MOS values, with S2- , S22- , S21- (and O2- , O1- , O22- , O21- )
ligands bonded by ionic, covalent, and correlative contributions. The known
tendencies toward lower MOS on going from oxides to sulfides, from Hs to Os to
Ru, and from Pu to Sm, and the specific behavior of Fe, were found to arise from
the different atomic orbital energies and radii of the (n-1)p core and (n-1)d and
(n-2)f valence shells of the metal atoms in row n of the periodic table. The
comparative results of the electronic and geometric structures of the MO4 and MS4
species provides insight into the periodicity of oxidation states and bonding.
PMID- 28516507
TI - An All-Plastic Field-Effect Nanofluidic Diode Gated by a Conducting Polymer
Layer.
AB - The design of an all-plastic field-effect nanofluidic diode is proposed, which
allows precise nanofluidic operations to be performed. The fabrication process
involves the chemical synthesis of a conductive poly(3,4-ethylenedioxythiophene)
(PEDOT) layer over a previously fabricated solid-state nanopore. The conducting
layer acts as gate electrode by changing its electrochemical state upon the
application of different voltages, ultimately changing the surface charge of the
nanopore. A PEDOT-based nanopore is able to discriminate the ionic species
passing through it in a quantitative and qualitative manner, as PEDOT nanopores
display three well-defined voltage-controlled transport regimes: cation
rectifying, non-rectifying, and anion rectifying regimes. This work illustrates
the potential and versatility of PEDOT as a key enabler to achieve
electrochemically addressable solid-state nanopores. The synergism arising from
the combination of highly functional conducting polymers and the remarkable
physical characteristics of asymmetric nanopores is believed to offer a promising
framework to explore new design concepts in nanofluidic devices.
PMID- 28516508
TI - Near-infrared photodynamic inactivation of S. pneumoniae and its interaction with
RAW 264.7 macrophages.
AB - Pneumonia is the main cause of children mortality worldwide, and its major
treatment obstacle stems from the microorganisms increasing development of
resistance to several antibiotics. Photodynamic therapy has been presenting, for
the last decades, promising results for some subtypes of cancer and infections.
In this work we aimed to develop a safe and efficient in vitro protocol for
photodynamic inactivation of Streptococcus pneumoniae, one of the most commonly
found bacteria in pneumonia cases, using two near-infrared light sources and
indocyanine green, a FDA approved dye. Photodynamic inactivation experiments with
bacteria alone allowed to determine the best parameters for microbial
inactivation. Cytotoxicity assays with RAW 264.7 macrophages evaluated the safety
of the PDI. To determine if the photodynamic inactivation had a positive or
negative effect on the natural killing action of macrophages, we selected and
tested fewer indocyanine green concentrations and 10 J/cm2 on macrophage-S.
pneumoniae co-cultures. We concluded that ICG has potential as a photosensitizer
for near-infrared photodynamic inactivation of S. pneumoniae, producing minimum
negative impact on RAW 264.7 macrophages and having a positive interaction with
the immune cell's microbicidal action.
PMID- 28516510
TI - Proteomic analysis of Lupinus angustifolius (var. Zeus and Bojar) and Lupinus
luteus (var. Lord and Parys) seed proteins and their hydrolysates.
AB - BACKGROUND: Proteins enzymatic digestion is a very complex process, during which
some components are degraded, whereas others remain in an unchanged form.
Moreover, enzymatic hydrolysis is one of the most popular methods used to reduce
the allergenicity of food proteins. In the present study, the efficiency of
enzymatic hydrolysis of lupin seed proteins was assessed by proteomic analysis as
performed by two-dimensional gel electrophoresis (2-DE) coupled with mass
spectrometry identification. Two digestion systems were used: oriented digestion
carried out by trypsin and model in vitro digestion mimicking the conditions
present in the gastrointestinal tract. RESULTS: The comparisons of 2-DE maps of
proteins isolated form different lupin seed species revealed that the differences
in proteins expression were observed mainly in the central parts of gels (i.e. in
the molecular weight range from 20 to 70 kDa, and the pH range 5-7). In total, 27
differentially expressed proteins spots were successfully identified by mass
spectrometry analysis. An important reduction in the number of proteins spots on
2-DE maps was observed when trypsin and the in vitro digestion model were
applied. The protein spot insensitive to digestion in both hydrolysis systems was
identified as beta-conglutin. CONCLUSIONS: The results of the present study
provide insight into the nature of the digestion process that may take place
after lupin seed protein intake and highlight the important fact that some of the
proteins are insensitive to digestive enzyme activity. Moreover, evaluation of
digestion activity of trypsin towards lupin seed proteins may be used for the
development of specific processes with respect to hypoallergenic food production.
(c) 2017 Society of Chemical Industry.
PMID- 28516511
TI - An Electrochemically Treated BiVO4 Photoanode for Efficient Photoelectrochemical
Water Splitting.
AB - BiVO4 films with (040) facet grown vertically on fluorine doped SnO2 (FTO) glass
substrates are prepared by a seed-assisted hydrothermal method. A simple
electrochemical treatment process drastically enhances the photocatalytic
activity of BiVO4 , exhibiting a remarkable photocurrent density of 2.5 mA cm-2
at 1.23 V vs. reversible hydrogen electrode (RHE) under AM 1.5 G illumination,
which is approximately 10-fold higher than that of the pristine photoanode.
Loading cobalt borate (CoBi) as cocatalyst, the photocurrent density of the BiVO4
photoanode can be further improved to 3.2 mA cm-2 , delivering an applied bias
photon-to-current efficiency (ABPE) of 1.1 %. Systematic studies reveal that
crystal facet orientation also synergistically boosts both charge separation and
transfer efficiencies, resulting in remarkably enhanced photocurrent densities.
These findings provide a facile and effective approach for the development of
efficient photoelectrodes for photoelectrochemical water splitting.
PMID- 28516509
TI - The incidence and predictors of depressive and anxiety symptoms in older adults
with vision impairment: a longitudinal prospective cohort study.
AB - PURPOSE: Depression and anxiety are highly prevalent in older adults with vision
impairment. Because symptoms of depression and anxiety appear to fluctuate, it is
important to identify patients who are at risk of developing these symptoms for
early diagnosis and treatment. Therefore, the aim of this study was to determine
the incidence of subthreshold depression and anxiety, and to investigate
predictors of developing symptoms of depression and anxiety in older adults with
vision impairment who had no subthreshold depression or anxiety at baseline.
METHODS: A longitudinal prospective cohort study with a follow-up of 24 months in
540 older adults with vision impairment (mean age 75 years, 56% female, 48%
macular degeneration, 15% glaucoma) from outpatient low-vision rehabilitation
organisations was performed. The cumulative incidences of subthreshold depression
and anxiety were calculated and linear mixed models with maximum likelihood
estimation were used to determine two prediction models. Main outcome measures
were: fluctuations in (i) depressive symptoms (Center for Epidemiologic Studies
Depression Scale, CES-D) and (ii) anxiety symptoms (Hospital Anxiety and
Depression Scale-Anxiety subscale, HADS-A). RESULTS: The annual cumulative
incidences of subthreshold depression and anxiety were 21.3% (95% Confidence
Interval (CI) 18.7-23.9%) and 9.5% (95% CI 7.4-11.6%), respectively. Risk factors
for developing depressive symptoms were: living alone, having just enough money
to cover expenses, having macular degeneration, having problems with adaptation
to vision loss, reduced health related quality of life, and experiencing symptoms
of anxiety. For developing anxiety symptoms, a relatively younger age,
experiencing symptoms of depression, not living alone and experiencing hindrance
at work proved to be risk factors. CONCLUSIONS: This study shows that the
incidence of subthreshold depression and anxiety in older adults with vision
impairment is twice as high compared with older adults in general and confirms
that depression and anxiety symptoms fluctuate over time. It is of great
importance that low vision rehabilitation staff monitor older adults with vision
impairment who are most vulnerable for developing these symptoms, based on the
risk factors that were found in this study, to be able to offer early
interventions to prevent and treat mental health problems in this population.
PMID- 28516512
TI - Defective alpha2 antiplasmin cross-linking and thrombus stability in a case of
acquired factor XIII deficiency.
AB - Acquired factor XIII (FXIII) deficiency is a rare and life-threatening condition
that is often misdiagnosed or missed completely. A 72-year-old woman presented
with symptoms of major unprovoked bleeding but routine coagulation screening
tests and platelet count were normal. Low activated FXIII (FXIIIa) activity
levels and abnormal urea clot stability led to diagnosis of acquired FXIII
deficiency. A modified Bethesda inhibitor titre of 1.6 Bethesda units/ml
indicated the presence of a FXIII inhibitor. Bleeding responded to a single dose
of FXIII concentrate and immunosuppression with prednisolone induced remission. A
subsequent relapse was treated with combined prednisolone and Rituximab resulting
in a prolonged, ongoing remission. Here we analyse the mechanisms underlying this
idiopathic case of acquired FXIII deficiency. Prospective analysis of patient
plasma revealed minimal FXIIIa activity and antigen in presentation and relapse
samples. Thrombi formed from these samples lysed rapidly and showed an absence of
cross-linked alpha2 AP. Western blotting revealed the presence of FXIII-B,
indicating only FXIII-A and FXIII-A2 B2 were affected. FXIII activity and antigen
levels normalised on remission. Our data suggest the presence of inhibitor
induced clearance of FXIII from plasma. As a consequence, reduced thrombus
stability was evident due to defective alpha2 AP cross-linking, thereby
explaining symptoms of excessive bleeding.
PMID- 28516513
TI - Evaluating an educational intervention to alleviate distress amongst men with
newly diagnosed prostate cancer and their partners.
AB - OBJECTIVE: To determine whether an education session alleviates distress for both
patients with prostate cancer and their partners; and whether their partner's
attendance at the session; and disease, treatment, and sociodemographic
characteristics affect changes in distress levels. PATIENTS, SUBJECTS AND
METHODS: We identified men with untreated prostate cancer at the Vancouver
Prostate Centre between February 2015 and March 2016 who agreed to attend our
education session. The session consisted of a didactic presentation covering the
biology of prostate cancer, treatment options, and side-effects, followed by a
private joint session with a urologist and radiation oncologist. We assessed
distress using the Distress Thermometer (DT) and compared pre- and post-session
distress, and change in distress between patients and partners using matched and
unmatched t-tests, respectively. We also assessed pre-session anxiety using the
seven-item Generalised Anxiety Disorder measure, and decisional certainty using
the Decisional Conflict Scale. RESULTS: In all, 71 patients and 48 partners
participated in the study. Attending the session led to a significant reduction
in the median DT score for patients (4.0-3.0, P < 0.01) and partners (5.0-4.0, P
= 0.02). Partners reported higher distress both before and after the session (4.9
vs 3.8, P = 0.03 pre-session and 4.2 vs 3.2, P = 0.03 post-session). The presence
of a partner at the session did not affect patients' pre- or post-session
distress or the success of the session at alleviating distress. Sociodemographic
and clinical characteristics had little effect on distress levels. CONCLUSIONS:
An interdisciplinary education session is equally effective at alleviating
distress for both patients with prostate cancer and their female partners.
PMID- 28516514
TI - Single-incision totally extraperitoneal inguinal hernia repair is feasible and
safe in patients on antithrombotic therapy: A single-center experience of 92
procedures.
AB - INTRODUCTION: The aim of this study was to evaluate the feasibility and safety of
SILS for totally extraperitoneal inguinal hernia repair for patients on
antithrombotic therapy. METHODS: A total of 365 patients who underwent SILS for
totally extraperitoneal inguinal hernia repair between January 2011 and November
2015 were analyzed retrospectively. Antithrombotic drugs were stopped
preoperatively, and bridging intravenous heparin therapy was given according to
the operative risk of each patient. Data on the patients' characteristics and
perioperative outcomes were collected from their medical records. RESULTS: Ninety
two patients (25%, 92/365) were treated with antithrombotic drugs preoperatively.
The mean operative times for unilateral and bilateral hernia repairs were 96 min
and 94 min (P = 0.5), respectively, in the antithrombotic therapy group and 140
min and 130 min (P = 0.2), respectively, in the control group. Bleeding volume
was minimal in all patients. There was no significant difference in the
conversion rate. The mean postoperative hospital stay was 2.5 days in the
antithrombotic therapy group and 2.1 days in the control group (P = 0.1).
Postoperative complications were seen in 16% (15/92) of patients in the
antithrombotic therapy group and in 11% (29/273) of patients in the control group
(P = 0.2). Pulmonary embolism was seen in one patient (0.4%, 1/273) in the
control group. CONCLUSIONS: SILS for totally extraperitoneal inguinal hernia
repair with bridging heparin therapy can be performed safely for patients on
antithrombotic therapy.
PMID- 28516515
TI - Interaction of lincRNA ROR and p53/miR-145 correlates with lung cancer stem cell
signatures.
AB - ROR is one of large intergenic non-coding RNAs (lincRNAs) and acts as a strong
negative regulator of p53 and a sponge for miR-145 to regulate diverse cancer
progression. However, the interaction of ROR, p53 and miR-145 in lung cancer and
its correlation with lung cancer stem cell (LCSC) signatures were not fully
understood. Here, qRT-PCR analysis revealed that p53 and ROR were upregulated
while miR-145 was downregulated in non-small cell lung cancer (NSCLC) tissues and
LCSCs compared to their paired adjacent normal tissues and lung cancer cells
(LCCs). Besides, high p53 level, low miR-145 level, and high ROR level were
associated with poor prognosis in NSCLC. Then, we found that silencing ROR failed
to change p53 mRNA level but promoted p53 protein level, suggesting a
posttranscriptional regulation mechanism involved in si-ROR-mediated promotion of
p53. While silencing p53 moderately downregulated ROR. Additionally, silencing
ROR or p53 upregulated miR-145. However, silencing both ROR and p53 failed to
make obvious change to miR-145 mRNA level and p53 protein level. And
interestingly, miR-145 negatively regulated Oct4 and Sox2. We also found that
silencing ROR and (or) p53 suppressed in vitro cell proliferation, migration and
invasion in LCSCs and LCCs. And suppression of endogenous ROR reduced the in vivo
tumor growth and metastasis of LCSCs. Our study demonstrated that ROR and p53/miR
145 correlated with prognosis in NSCLC as well as cell proliferation, migration,
invasion, and tumorigenicity of LCSCs, shedding new light on novel therapeutic
options in lung cancer. This article is protected by copyright. All rights
reserved.
PMID- 28516516
TI - Toward Long-Term Stable and Efficient Large-Area Organic Solar Cells.
AB - Here, we report that long-term stable and efficient organic solar cells (OSCs)
can be obtained through the following strategies: i) combination of rapid-drying
blade-coating deposition with an appropriate thermal annealing treatment to
obtain an optimized morphology of the active layer; ii) insertion of interfacial
layers to optimize the interfacial properties. The resulting devices based on
poly[4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)benzo[1,2-b;4,5-b']dithiophene-2,6
diyl-alt-(4-(2-ethylhexyl)-3-fluorothieno[3,4-b]thiophene-2-carboxylate-2,6
diyl)] (PBDTTT-EFT):[6,6]-phenyl C71 butyric acid methyl ester (PC71 BM) blend as
the active layer exhibits a power conversion efficiency (PCE) up to 9.57 %, which
represents the highest efficiency ever reported for blade-coated OSCs.
Importantly, the conventional structure devices based on poly(3-hexylthiophene)
(P3HT):phenyl-C61 -butyric acid methyl ester (PCBM) blend can retain
approximately 65 % of their initial PCE for almost 2 years under operating
conditions, which is the best result ever reported for long-term stable OSCs
under operational conditions. More encouragingly, long-term stable large-area
OSCs (active area=216 cm2 ) based on P3HT:PCBM blend are also demonstrated. Our
findings represent an important step toward the development of large-area OSCs
with high performance and long-term stability.
PMID- 28516520
TI - Poster - Thur Eve - 04: Online review of beam output and profile constancy using
statistical process control.
AB - The objective of this work was to create a comprehensive online tool to evaluate
and review the performance of quality assurance measurements that assess beam
output and profile constancy as soon as they are acquired using statistical
process control. As part of routine quality assurance: output, flatness and
symmetry measurements are acquired daily and weekly with DQA3 and the Matrix and
symmetry and flatness are acquired on a monthly basis with Profiler2. An
individuals control chart and a moving range control chart was plotted for each
set of data. Upper and lower control limits were calculated using measurements
acquired during a several month period when the linear accelerators were
operating optimally. The existing action levels, established according to TG142
and CAPCA guidelines were compared with the calculated statistical control
limits. Tighter tolerance limits were recommended for output, symmetry and
flatness Matrix measurements and DQA3 flatness measurements.
PMID- 28516518
TI - meta-C-H Arylation and Alkylation of Benzylsulfonamide Enabled by a
Palladium(II)/Isoquinoline Catalyst.
AB - Palladium(II)-catalyzed meta-C-H arylation and alkylation of benzylsulfonamide
using 2-carbomethoxynorbornene (NBE-CO2 Me) as a transient mediator are realized
by using a newly developed electron-deficient directing group and isoquinoline as
a ligand. This protocol features broad substrate scope and excellent functional
group tolerance. The meta-substituted benyzlsulfonamides can be readily
transformed into sodium sulfonates, sulfonate esters, and sulfonamides, as well
as styrenes by Julia-type olefination. The unique impact of the isoquinoline
ligand underscores the importance of subtle matching between ligands and the
directing groups.
PMID- 28516519
TI - Exercise training in Diastolic Heart Failure (Ex-DHF): rationale and design of a
multicentre, prospective, randomized, controlled, parallel group trial.
AB - Heart failure with preserved ejection fraction (HFpEF) is a common disease with
high incidence and increasing prevalence. Patients suffer from functional
limitation, poor health-related quality of life, and reduced prognosis. A pilot
study in a smaller group of HFpEF patients showed that structured, supervised
exercise training (ET) improves maximal exercise capacity, diastolic function,
and physical quality of life. However, the long-term effects of ET on patient
related outcomes remain unclear in HFpEF. The primary objective of the Exercise
training in Diastolic Heart Failure (Ex-DHF) trial is to investigate whether a 12
month supervised ET can improve a clinically meaningful composite outcome score
in HFpEF patients. Components of the outcome score are all-cause mortality,
hospitalizations, NYHA functional class, global self-rated health, maximal
exercise capacity, and diastolic function. After undergoing baseline assessments
to determine whether ET can be performed safely, 320 patients at 11 trial sites
with stable HFpEF are randomized 1:1 to supervised ET in addition to usual care
or to usual care alone. Patients randomized to ET perform supervised
endurance/resistance ET (3 times/week at a certified training centre) for 12
months. At baseline and during follow-up, anthropometry, echocardiography,
cardiopulmonary exercise testing, and health-related quality of life evaluation
are performed. Blood samples are collected to examine various biomarkers. Overall
physical activity, training sessions, and adherence are monitored and documented
throughout the study using patient diaries, heart rate monitors, and
accelerometers. The Ex-DHF trial is the first multicentre trial to assess the
long-term effects of a supervised ET programme on different outcome measures in
patients with HFpEF.
PMID- 28516521
TI - Poster - Thur Eve - 14: The effect of fluence and detector size on image quality
in multi-projection compton scatter tomography.
AB - PURPOSE: To assess how radiation dose and size of energy sensitive detectors
affects image quality in multi-projection Compton scatter tomography. METHODS AND
MATERIALS: A Compton scatter tomography system was simulated in Maltab. The
system consists of a point source generated x-ray fan beam and energy sensitive
photon counting detectors, placed along a line with the source outside the
periphery of the primary beam. Single scattered photons from a low contrast
phantom simulating breast tissues were simulated. Simulation parameters are dose
limited and closely matched to typical breast CT. Poisson distributed noise was
added to simulate quantum noise. RESULTS: We have successfully reconstructed
electron density images in a clinical fan-beam breast CT system, in the presence
of noise. The reconstruction illustrates accurate spatial alignment of the
structures of interest in the phantom. The increase in MSE due to noise was ~11%.
The optimal detector size of 2 * 2 mm2 is a trade off between the increased
noise, that is present when smaller detector sizes are used, and the blurring of
the image that occurs as larger detectors are employed. CONCLUSIONS: For breast
CT dose of 4-12 mGy, the optimal detector size for a Compton scatter
reconstruction using 360 projections and 1000 eV energy resolution was found to
be 2 * 2 mm2 . The ability to visualize large low contrast (9%) and small (2 mm
diameter) high contrast objects was demonstrated.
PMID- 28516522
TI - Sci-Thur PM: YIS - 07: Monte Carlo simulations to obtain several parameters
required for electron beam dosimetry.
AB - When current dosimetry protocols were written, electron beam data were limited
and had uncertainties that were unacceptable for reference dosimetry. Protocols
for high-energy reference dosimetry are currently being updated leading to
considerable interest in accurate electron beam data. To this end, Monte Carlo
simulations using the EGSnrc user-code egs_chamber are performed to extract
relevant data for reference beam dosimetry. Calculations of the absorbed dose to
water and the absorbed dose to the gas in realistic ion chamber models are
performed as a function of depth in water for cobalt-60 and high-energy electron
beams between 4 and 22 MeV. These calculations are used to extract several of the
parameters required for electron beam dosimetry - the beam quality specifier, R50
, beam quality conversion factors, kQ and kR50 , the electron quality conversion
factor, k'R50 , the photon-electron conversion factor, kecal , and ion chamber
perturbation factors, PQ . The method used has the advantage that many important
parameters can be extracted as a function of depth instead of determination at
only the reference depth as has typically been done. Results obtained here are in
good agreement with measured and other calculated results. The photon-electron
conversion factors obtained for a Farmer-type NE2571 and plane-parallel PTW Roos,
IBA NACP-02 and Exradin A11 chambers are 0.903, 0.896, 0.894 and 0.906,
respectively. These typically differ by less than 0.7% from the contentious TG-51
values but have much smaller systematic uncertainties. These results are valuable
for reference dosimetry of high-energy electron beams.
PMID- 28516523
TI - Poster - Thur Eve - 07: CNSC Update: "What's New in Class II".
AB - The Accelerators and Class II Facilities Division (ACFD) of the Canadian Nuclear
Safety Commission (CNSC), is responsible for the oversight of radiotherapy
facilities containing Class II prescribed equipment in Canada. This poster will
highlight a number of new initiatives that the CNSC has implemented recently that
have an impact on radiotherapy facility licensees. The presentation will discuss
the recent policy decision to regulate particle accelerators of above 1 MeV.
Challenges and progress with respect to the implementation of the policy will be
presented. Other initiatives which will be described include: * The new ACFD
webspace on the CNSC website, with direct links to relevant information on
licensing, compliance and Class II prescribed equipment * The improved structure
of the Appendix of Licence Documents that is part of every Class II licence *
Updated licence application guides * Changes to Annual Compliance reporting
requirements and progress on the ACR-Online initiative * Changes to some
regulatory expectations related to medical accelerator facilities * Consolidation
of Class II facility licences The poster will also include other initiatives that
may be of particular interest to COMP membership.
PMID- 28516524
TI - Sci-Thur AM: Planning - 07: A fast and accurate source model for energy and
intensity modulated electron beams.
AB - The purpose of this study is to develop a highly accurate and fast method for
calculating electron beam dose distributions in Modulated Electron Radiation
Therapy (MERT). An algorithm has been developed for creating phase-space files at
the exit of a linear accelerator for any arbitrary intensity and energy electron
beam without the need of full Monte Carlo simulations. The model assigns each
particle to one of the 3 following sources: primary, secondary collimator and
electron collimator scatter. The primary component is derived by fast MC
transport in air. The scatter components are derived by the use of MC pre
calculated leaf kernels. Each kernel includes the fluence distribution, energy
distribution and scatter probability of generating an electron from a leaf. The
original position is sampled from tunable Gaussian or uniform distributions. The
direction is estimated by geometrical means. According to the projection of the
direction a particle is rejected if it is expected to suffer a leaf-hit. A leaf
hit counter is used to calculate the output of scatter particles based on the pre
calculated scatter probabilities. To account for multiple coulomb scattering in
air a MC-corrected version of the Fermi-Eyges scattering theory was implemented.
Depth and profile dose distributions were derived for the largest and smallest
square field sizes, as well as for irregular and off-axis fields. The model
agreed with full MC dose distributions within 3 % in all cases. Output at the
depth of maximum dose exhibited discrepancies less than 2.6 % in all cases. The
model was 16-22 times faster in generating a phase-space file than a full MC
simulation with the BEAMnrc code.
PMID- 28516526
TI - Poster - Thur Eve - 01: Development of simple and fast EBT2 film calibration
procedure using PDD table.
AB - Standard calibration procedure for EBT films is laborious and time-consuming. The
objective of this work was to develop a simple and fast approach of EBT2 film
calibration using PDD tables. EBT2 sheet is cut into 3 stripes of 5*25.5cm2 . The
strips were exposed to dose of 600, 200 and 70cGy at dmax each while placed
horizontally in the middle of a 30*30*30cm3 solid water phantom. Varian 21EX 6MV
10*10cm2 beam was used with the gantry rotated to 90 degrees and SSD of 100cm to
the phantom surface. After at least 24 hours, the films were digitized with
flatbed scanner (Epson10000XL), according to a modified ISP scanning protocol.
All images were analysed using an in-house Matlab code and ImageJ software. The
net-optical densities against depths in the solid phantom were calibrated using
PDD tables measured with ionization chamber for same machine. For verification,
another calibration curve was generated for the same film batch following the
same calibration protocol. Seven pieces of films were exposed to known doses and
these doses were reconstructed using two derived calibration curves. The proposed
approach was 3.6 times faster than the standard considering the number of films
used in each methods, 3 stripes compared to11 pieces. The mean relative dose
difference calculated for these films using the PDD calibration and the standard
methods was 1.0+/-1.2% and 0.5+/-2.2% with maximum relative differences of 3.0%
and 4.7% respectively. Our results show that PDD calibration approach is much
easier, faster and predicts dose more reproducibly and accurately than the
standard approach.
PMID- 28516527
TI - Poster - Thur Eve - 11: A realistic respiratory trace generator and its
application to respiratory management techniques.
AB - Respiratory motion complicates radiotherapy treatment of thoracic and abdominal
tumours. Simplified respiratory motions such as sinusoidal and single patient
traces are often used to determine the impact of motion on respiratory management
techniques in radiotherapy. Such simplifications only accurately model a small
portion of patients, as most patients exhibit variability and irregularity beyond
these models. We have preformed a comprehensive analysis of respiratory motion
and developed a software tool that allows for explicit inclusion of variability.
We utilize our realistic respiratory generator to customize respiratory traces to
test the robustness of the estimate of internal gross target volumes (IGTV) by
4DCT and CBCT. We confirmed that good agreement is found between 4DCT and CBCT
for regular breathing motion. When amplitude variability was introduced the
accuracy of the estimate slightly, but the absolute differences were still < 3 mm
for both modalities. Poor agreement was shown with the addition of baseline
drifts. Both modalities were found to underestimate the IGTV by as much as 30%
for 4DCT and 25% for CBCT. Both large and small drifts deteriorated the estimate
accuracy. The respiratory trace generator was advantageous for examining the
difference between 4DCT and CBCT IGTV estimation under variable motions. It
provided useful implementation abilities to test specific attributes of
respiratory motion and detected issues that were not seen with the regular motion
studies. This is just one example of how the respiratory trace generator can be
utilized to test applications of respiratory management techniques.
PMID- 28516528
TI - Sci-Thur AM: Planning - 11: The impact of distributed calculation framework
settings on plan calculation time.
AB - Some treatment planning system can divide a treatment plan calculation into
multiple threads and allow both local and network computing resources to perform
the calculation concurrently, which significantly reduces the calculation time
for a calculation-demanding planning such as Volumetric Modulated Arc Therapy
(VMAT) or electron Monte Carlo (eMC). This study tested in Eclipse (Varian,
V10.0.39) the impact of Distributed Calculation Framework (DCF, V10.0.0.757)
settings on calculation time in a planning environment that consists of 20
workstations with 8 core processors and 16GB RAMs installed on most of them. It
is found that for an arc plan increasing the control point field parallelization
factor reduces the total calculation time at beginning but lengthens the total
calculation time after a certain level as a result of data sending time increase.
Further increasing the factor may cause a serious net work traffic or even
failure of a calculation. For an eMC plan the calculation time decreases
monotonously with the increase of Monte carlo field parallelization factor, and
the data sending time is insignificant compared to the calculation time.
Increasing the local servant numbers reduces the data sending time but raises the
calculation time for arc and eMC plans. The calculation time increment is more
and more significant with the increase of local servants. The optimal DCF setting
for a facility depends on the total number of calculation workstations available,
the hardware configuration of the workstations, and the data transfer rate of the
network. No conflict of interest exists in the study.
PMID- 28516529
TI - Sci-Thur AM: Planning - 04: Evaluation of the fluence complexity, solution
quality, and run efficiency produced by five fluence parameterizations
implemented in PARETO multiobjective radiotherapy treatment planning software.
AB - PURPOSE: PARETO (Pareto-Aware Radiotherapy Evolutionary Treatment Optimization)
is a novel multiobjective treatment planning system that performs beam
orientation and fluence optimization simultaneously using an advanced
evolutionary algorithm. In order to reduce the number of parameters involved in
this enormous search space, we present several methods for modeling the beam
fluence. The parameterizations are compared using innovative tools that evaluate
fluence complexity, solution quality, and run efficiency. METHODS: A PARETO run
is performed using the basic weight (BW), linear gradient (LG), cosine transform
(CT), beam group (BG), and isodose-projection (IP) methods for applying fluence
modulation over the projection of the Planning Target Volume in the beam's-eye
view plane. The solutions of each run are non-dominated with respect to other
trial solutions encountered during the run. However, to compare the solution
quality of independent runs, each run competes against every other run in a round
robin fashion. Score is assigned based on the fraction of solutions that survive
when a tournament selection operator is applied to the solutions of the two
competitors. To compare fluence complexity, a modulation index, fractal
dimension, and image gradient entropy are calculated for the fluence maps of each
optimal plan. RESULTS: We have found that the LG method results in superior
solution quality for a spine phantom, lung patient, and cauda equina patient. The
BG method produces solutions with the highest degree of fluence complexity. Most
methods result in comparable run times. CONCLUSION: The LG method produces
superior solution quality using a moderate degree of fluence modulation.
PMID- 28516530
TI - Measurement and Detection of Radiation.
PMID- 28516533
TI - Poster - Thur Eve - 03: LDR to HDR: RADPOS applications in brachytherapy.
AB - The RADPOS in vivo dosimetry system combines an electromagnetic positioning
sensor and either one or five MOSFET dosimeters. The feasibility of using the
system for quality control has been explored for a range of radiotherapy
treatment techniques including most recently transperineal interstitial permanent
prostate brachytherapy and high dose rate (HDR) treatments. Dose and position
information was collected by a RADPOS array detector inside a Foley catheter
within patients' urethra during permanent seed implantation. Ten patients were
studied, and average displacement during implantation was Deltar = (1.4-5.1) mm,
with movements up to 9.7 mm due to the removal of the transrectal ultrasound
probe. Maximum integral dose in the prostatic urethra ranged from 110-195 Gy, and
it was found that the dose can change up to 63 cGy (62.0%) depending on whether
the rectal probe is in place. For HDR, a RADPOS detector was first calibrated
with an Ir-192 source. A treatment was then simulated using a total of 50 dwell
positions in 5 catheters in an acrylic phantom. Dwell positions ranged from 1 to
10 cm away from the RADPOS detector and dose was measured for each source
position. An average calibration coefficient of 0.74+/-0.11 cGy/mV was calculated
for the detector and the average absolute difference between measured values and
expected dose was 0.7+/-5.4 cGy (5+/-20%). The demonstrated accuracy of RADPOS
dose measurements along with its ability to simultaneously measure displacement
makes it a powerful tool for brachytherapy treatments, where high dose gradients
can present unique in vivo dosimetry challenges.
PMID- 28516535
TI - Sci-Thur PM: YIS - 06: Effect of the k-space sampling pattern on the MTF of
compressed sensing MRSI.
AB - Compressed Sensing MRSI (CS-MRSI) offers the ability to accelerate MRSI sequences
while suffering minimal artifacts compared to conventional fast MRSI techniques.
CS-MRSI exploits the inherent sparsity of MRSI images and incoherent artifacts of
pseudo-random sub-Nyquist sampling of k-space combined with non-linear
reconstruction to produces MRSI images. CS-MRSI can be used as an acceleration
tool to decrease the scan time while maintaining acceptable spatial definition or
to enable the acquisition of higher resolution scans while minimizing the
associated time penalty. In this work we adopt the compressed sensing technique
to accelerate a clinically relevant 2-D point resolved spectroscopy sequence.
However, the process of weighing the cost and benefit of applying such a fast
imaging technique is complicated due to the unique non-linear nature of the
reconstruction process and has largely relied on qualitative assessments.
Moreover, pseudo-random sub-Nyquist sampling of k-space can have unwanted effects
on the modulation transfer function. In this work we set out to quantify the loss
in image quality associated with CS-MRSI. We used simulations of a phantom based
method to investigate the MTF behaviour of CS-MRSI with regard to different k
space sampling patterns. As expected, the k-space sampling patterns tested were
found to have a direct effect on the MTFs. Moreover, limiting the deviation of
the resulting k-space sampling pattern from the prescribed probability
distribution function had a positive effect on the MTF overall. Not only was low
resolution response improved, but we also noticed an improvement of ~ 26% in
resolution at 0.1 MTF.
PMID- 28516534
TI - Poster - Thur Eve - 13: Quantifying specific absorption rate of shielded RF coils
through electromagnetic simulations for 7-T MRI.
AB - Ultra-high field MRI has many advantages such as increasing spatial resolution
and exploiting contrast never before seen in-vivo. This contrast has been shown
to be beneficial for many applications such as monitoring early and late effect
to radiation therapy and transient changes during disease to name a few. However,
at higher field strengths the RF wave, needed to for transmitting and receiving
signal, approaches that of the head. This leads to constructive and
deconstructive interference and a non -uniform flip angle over the volume being
imaged. A transmit or transceive RF surface coil arrays is currently a method of
choice to overcome this problem; however, mutual inductance between elements
poses a significant challenge for the designer. A method to decouple elements in
such an array is by using circumferential shielding; however, the potential
benefits and/or disadvantages have not been investigated. This abstract primarily
focuses on understanding power deposition - measured through Specific Absorption
Rate - in the sample using circumferentially shielded RF coils. Various
geometries of circumferentially shielded coils are explored to determine the
behaviour of shield width and its effect on required transmit power and power
deposition to the sample. Our results indicate that there is an optimization on
shield width depending on the imaging depth. Additionally, the circumferential
shield focuses the field more than unshielded coils, meaning that slight SAR may
even be lower for circumferential shielded RF coils in array.
PMID- 28516536
TI - Poster - Thur Eve - 17: Control point analysis comparison of three different
treatment planning and delivery complexity levels using a commercial three
dimensional diode array.
AB - PURPOSE: To use Control Point Analysis (Sun Nuclear Corporation, Melbourne,
Florida, USA) to analyze and compare delivered VMAT plans for three different
treatment planning complexity levels. METHODS: Nineteen patients were chosen and
fully anonymized for the purpose of this study. Ten SBRT, six H&N, one breast and
two prostate VMAT plans were generated on Pinnacle3 and delivered on a Varian
LINAC. The delivered dose was measured using ArcCHECKTM. Each plan was analyzed
using SNC Patient 6 and Control Point Analysis. Gamma passing percentage was used
to assess the differences between the measured and planned dose distributions and
to assess the role of various control point binning scenarios. RESULTS: The
prostate cases reported the highest gamma passing percentages for SNC Patient 6
(99.3%-99.5%,3%/3mm) and Control Point Analysis (99.1--99.3%,3%/3mm). The mean
percentage of passing control point sectors for the prostate cases increased from
48.9+/-3.1% for individual control points to 69.5 +/- 3.9% for 5 control points
binned together to 100+/-0% for 10 control points binned together. Over all,
there was a trend in the percentage of sectors passing gamma analysis increasing
with the increase of the number of control points binned together in one sector
for both passing criteria considered (48.9+/-3.1% for individual control points
to 69.5+/-3.9% for 5 control points binned together in one sector to 100+/-0% for
10 control points binned together in one sector for the prostate). CONCLUSION:
The delivery accuracy per control point depends on the MU/control point (SBRT)
and the plan degree of modulation (H&N).
PMID- 28516537
TI - Sci-Thur AM: Planning - 06: Planning target volume margin suitability in lung
stereotactic body radiation therapy: A preliminary evaluation using cone-beam
computed tomography.
AB - Stereotactic body radiation therapy (SBRT) requires precise delivery of radiation
to the target; intra- and inter-fraction lung tumour motion may adversely impact
local tumour control. The purpose of this study was to retrospectively evaluate
the impact of planning target volume (PTV) margin size on the coverage of the
internal target volume (ITV) as localized in pre- and post-treatment cone-beam
computed tomography (CBCT) images. Data from two patients undergoing SBRT were
evaluated. For planning, free-breathing and 4DCT scans were performed, and used
to contour the ITV. A 5mm margin was added to create the PTV. During treatment,
14 CBCTs were collected pre- and post-beam delivery. A data set comprising the
average 4DCT intensities where available and treatment planning CT intensities
for voxels that were beyond the field of view of the 4DCT was constructed.
Registration of the combined planning image to each CBCT was performed using a
deformable image registration algorithm. The transformations aligning the
combined planning image with the CBCTs were applied to the planning ITV to obtain
the treatment ITVs. For each CBCT, the fraction of treatment ITV within the PTV
was determined using Boolean logic. This was repeated for various PTV margins
ranging from 0 to 10 mm at 1mm intervals. The 3 and 5 mm PTV margins covered 95.1
+/- 5.9% and 99.0 +/- 2.0% of the ITV, respectively. Analysis of additional
patients will be performed to confirm these preliminary results, which reinforce
the use of a 5mm PTV margin for lung SBRT.
PMID- 28516538
TI - Sci-Thur PM: YIS - 10: A new optically encoded single-fiber plastic scintillation
detector for multi-point radiation dosimetry.
AB - PURPOSE: To develop a new multi-point plastic scintillation detector (mPSD) that
allows for simultaneous dose measurements at multiple points and uses a single
optical guide. MATERIALS AND METHODS: Two different prototypes were built. A two
point mPSD was built and light discrimination was based on the use of multiple
color filters at the outputs of a network of optical fiber splitters. Light
intensity was measured by an EMCCD camera. For the three-point mPSD, the light
discrimination setup was replaced by a low-noise spectrometer. Depth-dose and
profiles measurements were obtained on a 6 MV photon beam with the mPSDs inside a
water phantom. An ion chamber was also used for comparison purpose. Finally, the
three-point mPSD was tested under an Ir-192 high-dose-rate (HDR) brachytherapy
dose delivery and compared to the treatment planning system. RESULTS: A good
agreement was found between the measured and expected dose for both mPSDs. The
average relative differences to the ion chamber measurement for the two-point
mPSD were of (2.4 +/- 1.6)% and (1.3 +/- 0.8)%. For the three-point mPSD, these
differences were of (2.3+/-1.1)%, (1.6+/-0.4)% and (0.32+/-0.19)%. The latter
mPSD was shown very versatile, being able to measure dose from HDR brachytherapy
with an average accuracy of (2.3+/-1.0)% per catheter. CONCLUSIONS: The practical
feasibility of mPSDs using a single optical guide has been demonstrated under
irradiation from a 6 MV photon beam and an Ir-192 HDR brachytherapy source. Their
application for pre-treatment quality assurance and in vivo dosimetry will be
various.
PMID- 28516539
TI - Poster - Thur Eve - 10: Long term stability of VMAT quality assurance parameters
using an EPID.
AB - The rapidly growing use of volumetric modulated arc therapy (VMAT) treatments in
radiation therapy calls for a quantitative, automated, and reliable quality
assurance (QA) procedure that can be used routinely in the clinical setting. In
this work, we present a series VMAT QA procedures used to assess dynamic multi
leaf collimator (MLC) positional accuracy, variable dose-rate accuracy, and MLC
leaf speed accuracy. The QA procedures were performed using amorphous silicon
electronic portal imaging devices (EPID) to determine the long term stability of
the measured parameters on two Varian linear accelerators. The measurements were
repeated weekly on both linear accelerators for a period of three months and the
EPID images were analyzed using custom Matlab software. The results of the picket
fence tests indicate that MLC leaf positions can be identified to within 0.11 mm
and 0.15 mm for static gantry delivery and VMAT delivery respectively. In
addition, the dose-rate, gantry speed and MLC leaf speed tests both show very
good stability over the measurement period. The measurements thus far, suggest
that a number of the dosimetry tests may be suitable for quarterly QA for Varian
iX and Trilogy linacs. However, additional measurements are required to confirm
the frequency with which each test is required for safe and reliable VMAT
delivery at our centre.
PMID- 28516540
TI - Sci-Thur AM: Planning - 10: Improved dosimetric accuracy for patient specific
quality assurance using a dual-detector measurement method for cyberknife output
factors.
AB - The measurement of output factors for small fields is challenging and can lead to
large dose errors in patient treatments if corrections for detector size and
scatter from high-Z material are not applied. Due to its high spatial resolution
and near tissue equivalence, GAFCHROMIC(r) film potentially provides a correction
free measure of output factors but it can be challenging to obtain high quality
dosimetric results using this film. We propose minimizing errors in the clinical
determination of small field output factors by employing diode measurements with
Monte-Carlo generated corrections for small fields <=10 mm diameter and using
small volume ion chambers for apertures >10 mm diameter with independent
validation using radiochromic film. We performed patient specific quality
assurance (QA) measurements for 9 patients using GAFCHROMIC(r) film and an A16
small volume ion chamber in a head-shaped phantom, employing this hybrid dual
detector method for relative output factor measurements within the Multiplan
treatment planning system. Our results suggest that consistent output factors can
be determined using this method with experimental verification using
GAFCHROMIC(r) film dosimetry. For the patient specific QA using film, we achieve
good dosimetric agreement (<2sigma) of the measured and calculated average dose
for pixels within the 80% isodose line. For patient specific QA using the micro
ion chamber, we get good agreement (<3%) for cone sizes greater than 5 mm. The
differences observed for the 5 mm cone plans are consistent with a 1 mm radial
setup uncertainty for patient positioning using the Cyberknife system.
PMID- 28516541
TI - Sci-Thur AM: Planning - 03: Extensive patient specific QA for field junction
regions for craniospinal irradiation with Jagged-Junction IMRT approach without
beam edge matching for field junctions.
AB - PURPOSE: Jagged-Junction IMRT was developed for craniospinal irradiation. An
extensive QA was performed for the field junction regions. METHODS AND MATERIALS:
The Jagged-Junction IMRT plan employed three field sets, each with unique
isocentres (Iso1,2,3). Fields from adjacent sets were overlapped and the dose was
smoothly integrated inside the overlapped junction. The delivered dose in the
junction regions were verified with film and ion chamber measurements on
phantoms. An anthropomorphic-wax phantom was created for verifying the cranio
spinal junction. For measuring at the spinal-spinal junction, a solid water
phantom was used. The influence of beam mismatching due to setup and mechanical
inaccuracy was investigated by shifting all the fields from Iso1 and Iso3
superiorly and inferiorly by 3 mm and at the same time keeping all the fields
from Iso2 without any shift. RESULTS: The patient-averaged difference between the
measured dose with ion chamber and planned dose in the cranio-spinal junction is
0.34 % +/- 0.40% and in the spinal-spinal junction this difference is 0.03% +/-
0.71%. The dose profile comparison shows that measured and planned dose profiles
match well to each other over a junction region. The patient-averaged dose
difference discrepancy between the film measurement and the planned is 1.1% +/-
1.3% at the cranio-spinal junction and -0.14% +/- 1.8% at the spinal junction.
CONCLUSIONS: Jagged-Junction IMRT planning provided smooth dose coverage to the
target in the field junction region. The junction dose for the Jagged-Junction
IMRT plan is not sensitive to the setup error during the treatment.
PMID- 28516542
TI - Sci-Thur PM: YIS - 02: A validated approach for clinical linacs to accurately
determine the photon spectra and the incident electron energy.
AB - In clinical photon beams, independent determination of the photon spectra and the
incident electron energy is useful for beam (re)commissioning and for detector
response modelling. In this study, an approach is developed for that purpose, and
validated on a research linac whose photon spectra and electron beams are
directly and independently known. In this approach, an optimized combination of
transmission curves is measured using multiple attenuators and detectors to
maximize energy differentiation. For validation, transmission measurements are
made for 8 beams from 10-30 MV, with bremsstrahlung targets from Be to Pb. A
protocol is established to account for many influence quantities including linac
drifts (2%), polarity (6%), ion recombination (0.2%), leakage (0.3%), room
scatter (0.8%), non-ideal attenuation (1.5%), attenuator mass thickness (4%), and
photonuclear effect (5.6%). The experimental accuracy on the smallest signals is
0.4%. EGSnrc is upgraded to model photonuclear attenuation (without tracking
secondary particles), and then used to model the full experiment. For direct
transmission comparisons, the agreement is 2%. This allows for an estimate of
0.5% on the upper limit of photon cross section uncertainties, which is much
better than the current estimate of 1-2%. The unfolded spectra agree with the
benchmark ones within 4.5%. The incident electron energy is accurate within 5%,
with 95% confidence. The overall improvement over the commonly used methods is a
factor of 3. This transmission study is the first to independently determine the
incident electron energy, and to recognize the significant role of the
photonuclear effect at higher energies.
PMID- 28516544
TI - Poster - Thur Eve - 12: Dosimetric manifestation of harmonic mode imaging for
seed implant brachytherapy.
AB - PURPOSE: To demonstrate the dosimetric effects of observer variability in
defining the prostate and critical organs, using Tissue Harmonic (H) ultrasound
imaging mode for permanent seed implant brachytherapy. METHODS: Images were
acquired using a B -K medical 8848 probe with Brightness (B) and H mode for ten
prostate brachytherapy patients. The prostate, rectum and urethra were contoured
independently by five observers. The clinically used treatment plans based on B
mode imaging fulfilling the dosimetric criteria were applied on these contours.
Dosimetric parameters (prostate: D90, V100 and V200; rectum: V100; urethra: V140,
V150 and V160) were computed using SPOT PROTM planning system. Interobserver
variability in dosimetric parameters was tested using standard deviations as
percentages of means. RESULTS: Two-factor analysis of variances showed
significant (p<0.05) interobserver variability in all dosimetric parameters for
both modes. Interobserver agreement in dosimetric parameters improves in H mode
due to improved interobserver consistency in contouring these organs on H mode
images compared to B mode. There is no significant difference observed (paired
student t test, p>0.05) in the mean values of dosimetric parameters in H and B
mode for prostate and critical organs. CONCLUSIONS: H mode due to its better
image quality helped to improve the interobserver agreement in contouring the
prostate and critical organs and hence better interobserver consistency in all
dosimetric parameter. Because the difference in the mean value of dosimetric
parameters between two imaging modes is not statistically significant, H mode
does not appear to offer any clinical advantages in terms of improving the
dosimetric outcome.
PMID- 28516545
TI - Sci-Thur PM: YIS - 05: Tomographic dosimetry using scintillating fibers and its
application to 2D and 3D dosimetry.
AB - PURPOSE: To present the proof of concept and the experimental validation of
tomographic dosimetry (tomodosimetry), where a tomographic acquisition of the
incident deposited dose is performed using long scintillating fibers. METHOD: 2D
tomodosimetry: 50 long scintillating fibers were aligned on a 20cm diameter disk
inside a 30cm diameter masonite phantom. 3D tomodosimetry: 128 long scintillating
fibers of various orientation were simulated on the surface of two cylindrical
regions of radius 7.5 and 3.75cm inside a 20cm diameter, 20cm long cylindrical
phantom. In both case, the dose projections were acquire each 5 degrees over a
180 degrees (2D) or 360 degrees (3D) rotation of the device, and the dose in each
scintillating fiber plane was reconstructed using a total variation minimization
reconstruction iterative algorithm at a resolution of 1*1mm2 . The 3D dose was
obtained by interpolating between in each cylindrical plane in the 3D prototype.
RESULTS: 3%/3mm gamma tests conducted in the isocentre plane for both
configurations achieved a success rate of more than 99% of the dose pixels in the
region over 50% of the maximum dose. Absolute dose differences in the high dose
low gradient region of each scintillating fiber plane were on average below 1%
for the 2D configuration and below 1.3% for the 3D configuration. CONCLUSIONS:
This work illustrates the potential and capacity of scintillating fiber based 2D
and 3D tomodosimeters. The presented methodology allows for millimeter resolution
dosimetry in a whole 2D plane or 3D volumes in real-time using only a limited
number of detectors.
PMID- 28516546
TI - Poster - Thur Eve - 06: Comparison of an open source genetic algorithm to the
commercially used IPSA for generation of seed distributions in LDR prostate
brachytherapy.
AB - In early stage prostate cancer, low dose rate (LDR) prostate brachytherapy is a
favorable treatment modality, where small radioactive seeds are permanently
implanted throughout the prostate. Treatment centres currently rely on a
commercial optimization algorithm, IPSA, to generate seed distributions for
treatment plans. However, commercial software does not allow the user access to
the source code, thus reducing the flexibility for treatment planning and
impeding any implementation of new and, perhaps, improved clinical techniques. An
open source genetic algorithm (GA) has been encoded in MATLAB to generate seed
distributions for a simplified prostate and urethra model. To assess the quality
of the seed distributions created by the GA, both the GA and IPSA were used to
generate seed distributions for two clinically relevant scenarios and the quality
of the GA distributions relative to IPSA distributions and clinically accepted
standards for seed distributions was investigated. The first clinically relevant
scenario involved generating seed distributions for three different prostate
volumes (19.2 cc, 32.4 cc, and 54.7 cc). The second scenario involved generating
distributions for three separate seed activities (0.397 mCi, 0.455 mCi, and 0.5
mCi). Both GA and IPSA met the clinically accepted criteria for the two
scenarios, where distributions produced by the GA were comparable to IPSA in
terms of full coverage of the prostate by the prescribed dose, and minimized dose
to the urethra, which passed straight through the prostate. Further, the GA
offered improved reduction of high dose regions (i.e hot spots) within the
planned target volume.
PMID- 28516547
TI - Poster - Thur Eve - 16: Four-dimensional x-ray computed tomography and
hyperpolarized 3 He magnetic resonance imaging of gas distribution in lung
cancer.
AB - Dynamic imaging methods such as four-dimensional computed tomography (4DCT) and
static imaging methods such as noble gas magnetic resonance imaging (MRI) deliver
direct and regional measurements of lung function even in lung cancer patients in
whom global lung function measurements are dominated by tumour burden. The
purpose of this study was to directly compare quantitative measurements of gas
distribution from static hyperpolarized 3 He MRI and dynamic 4DCT in a small
group of lung cancer patients. MRI and 4DCT were performed in 11 subjects prior
to radiation therapy. MRI was performed at 3.0T in breath-hold after inhalation
1L of hyperpolarized 3 He gas. Gas distribution in 3 He MRI was quantified using
a semi-automated segmentation algorithm to generate percent-ventilated volume
(PVV), reflecting the volume of gas in the lung normalized to the thoracic cavity
volume. 4DCT pulmonary function maps were generated using deformable image
registration of six expiratory phase images. The correspondence between identical
tissue elements at inspiratory and expiratory phases was used to estimate
regional gas distribution and PVV was quantified from these images. After
accounting for differences in lung volumes between 3 He MRI (1.9+/-0.5L
ipsilateral, 2.3+/-0.7 contralateral) and 4DCT (1.2+/-0.3L ipsilateral, 1.3+/
0.4L contralateral) during image acquisition, there was no statistically
significant difference in PVV between 3 He MRI (72+/-11% ipsilateral, 79+/-12%
contralateral) and 4DCT (74+/-3% ipsilateral, 75+/-4% contralateral). Our results
indicate quantitative agreement in the regional distribution of inhaled gas in
both static and dynamic imaging methods. PVV may be considered as a regional
surrogate measurement of lung function or ventilation.
PMID- 28516549
TI - Sci-Thur PM: YIS - 09: Development of a graphite probe calorimeter for absolute
clinical dosimetry: Numerical design optimization, prototyping and experimental
proof-of-concept.
AB - In this work, the feasibility of absolute dose to water measurements using a
small-scale graphite probe calorimeter (GPC) in a clinical environment is
established. A numerical design optimization study was conducted by simulating
the heat transfer in the GPC resulting from irradiation using a finite element
method software package. The choice of device shape, dimensions and materials was
made to minimize the heat loss in the sensitive volume of the GPC. The resulting
design, which incorporates a novel aerogel-based thermal insulator, was built in
house. Absorbed dose to water measurements were made under standard conditions in
a 6 MV 1000 MU/min photon beam and subsequently compared against TG-51 derived
values. The average measured dose to water was 95.7 +/-1.4 cGy/100 MU, as
compared to an expected value of 96.6 cGy/100 MU. The Monte Carlo-calculated
graphite to water dose conversion factor was 1.099, while the derived heat loss
correction factors varied between 1.005 and 1.013. The most significant sources
of uncertainty were the repeatability (type A, 1.4%) and thermistor calibration
(type B, 2.1%). The contribution of these factors to the overall uncertainty is
expected to decrease significantly upon the implementation of active thermal
stabilization provided by a temperature controller and direct electrical
calibration, respectively. This work demonstrates the feasibility of using the
GPC as a practical clinical absolute photon dosimeter and will serve as the basis
for a miniaturized version applicable to small and composite fields.
PMID- 28516548
TI - Sci-Thur AM: Planning - 05: Lung SBRT: Dosimetric accuracy of the Analytical
Anisotropic Algorithm (AAA) for 6MV FFF RapidArc planning.
AB - PURPOSE: Stereotactic Body Radiation Therapy (SBRT) requires the delivery of a
high biologically effective dose in only a few fractions. These large doses per
fraction can necessitate long treatment times. The Varian Truebeam is capable of
RapidArc delivery and also has the optional Flattening Filter Free (FFF) modes
which greatly increase the dose rate. We have commissioned the 6MV FFF beam (1400
MU/min) for RapidArc lung SBRT, and verified heterogeneous dose calculations with
Monte Carlo (MC). METHODS: The standard commissioning data was acquired for
Varian's Analytical Anisotropic Algorithm (AAA) beam model. Measurements were
acquired with the IBA Blue Phantom, using the CC13 and CC01 ion chambers and PTW
diode. MLC-defined fields were also acquired for model verification. The
Dosimetric Leaf Gap (DLG) was measured and then optimized using RapidArc lung
SBRT plans, matching Eclipse with ion chamber measurements. Heterogeneous dose
calculations were independently verified using MC. RESULTS: There were some
discrepancies regarding leaf transmission and penumbra, but the AAA model was
generally well within 2% and 2 mm. A nominal DLG value of 1.6 mm was chosen. A
representative lung SBRT case utilizing FFF RapidArc was calculated with MC. For
the high dose region, 99% matched Eclipse within 3% and 3 mm. The mean dose
difference of the PTV was 0.7%. CONCLUSIONS: Although we have observed some minor
infield discrepancies between the AAA and Monte Carlo calculations in
heterogeneous media, the Eclipse AAA is reasonably accurate for complex FFF,
RapidArc, SBRT lung planning.
PMID- 28516550
TI - Poster - Thur Eve - 09: Novel radiation safety challenges of a brachytherapy
redevelopment at the Credit Valley Hospital.
AB - Carlo Fidani Peel Regional Cancer Center at the Credit Valley Site of the Credit
Valley Hospital and Trillium Health Center is currently undergoing a
redevelopment to build a brachytherapy suite and associated areas with a
projected start date of April 2013. The new brachytherapy suite will be located
in the PRCC, and is a redevelopment of office area into clinical space. The
workload for the full brachytherapy program is expected to be 20 patients per
week, in cervix, prostate, skin, lung and other sites. There were challenges for
shielding due services in the slab to the renal clinic located above the
redevelopment area. The presence of over 30 voids in the slab and upper walls
made the solution to add shielding to the underside of the current slab
unsuitable. To overcome this, a second ceiling built below the slab to allow for
an uninterrupted shielding for the brachytherapy suite. The additional ceiling
allows for a crawl space between slab and shielding allowing for servicing if
needed for the drains from the renal clinic. The appropriate finalized shielding
design is 69mm of lead brick supported by steel plate and steel beams. Final
shielding for the walls is 690mm of concrete that allows public access to all
hallways around the facility. The final design for the new brachytherapy site at
the PRCC all services for the room are located within the shielding and all
services for areas outside the room are located outside the shielding.
PMID- 28516552
TI - Sci-Thur AM: Planning - 09: Assessing dynamic IMRT field modulation in prostate
plans.
AB - In a previous study, the variogram fractal dimension (FD) method was found to be
very accurate at identifying planned head and neck IMRT fields that are overly
modulated. In the current study, the authors used MATLAB(r) to develop FracMod, a
graphical user interface (GUI) and variogram FD analysis tool to assess
modulation complexity of dynamic IMRT fields designed for treatments of the
prostate alone and prostate plus pelvic nodes. A set of 5 prostate plans (25
fields) and 5 prostate plus pelvic node plans (35 fields) were used to choose FD
cut-points that ensure no false positives (100% specificity) in distinguishing
between moderate field modulation (typical modulation used clinically at the
authors' institution) and high modulation. Field modulation was controlled by
adjusting fluence smoothing parameters in the EclipseTM treatment planning
system. The area under the curve (AUC) from receiver operating characteristic
(ROC) analysis was used to quantitatively compare the ability of FD and the
number of monitor units (MUs) for distinguishing between the moderate and high
modulation fields. The variogram FD method gave AUCs of 0.96 (almost perfect
classification) and 1.00 (perfect classification) for the prostate alone and the
prostate plus pelvic node fields, respectively. The variogram FD method is an
accurate metric; performing better than the number of MUs at identifying high
modulation IMRT fields planned for the treatment of prostatic carcinoma. Hence,
FracMod will enable Radiotherapy Physicists to easily and accurately quantify the
degree of modulation of IMRT fields and adjust overly-modulated fields at the
treatment planning stage.
PMID- 28516553
TI - Sci-Thur AM: Planning - 02: Validation of XiO's eMC module using Gafchromic EBT3
films and triple channel dosimetry.
AB - The aim of this study is to validate the electron Monte Carlo module implemented
in XiO, a treatment planning system commercialized by Elekta CMS inc. Two types
of phantoms were investigated: homogeneous water phantoms with irregular surfaces
and phantoms containing slab and 3D heterogeneities. The phantoms were CT
scanned, and dose to water calculations were performed in the eMC module using 2
*2 * 2 mm2 voxels and a mean relative statistical uncertainty of 0.5%.
Concurrently, Gafchromic EBT3 film measurements were performed in the same
phantoms. To obtain reliable absolute dose readings from the films, a new method
using triple channel dosimetry in the Film QA Pro software was developed. The
accuracy of the proposed method was determined empirically and an uncertainty of
+/-1.5% was found over the range [75, 800] cGy. Dose comparisons between film and
simulations were done using an in-house MATLAB program. XiO's eMC module provides
accurate dose distributions in the presence of surface irregularities and slab
heterogeneities for 12 MeV beams. In the presence of 3D heterogeneities, the
percent dose difference comparisons highlighted the need to perform 3D gamma
comparisons. In conclusion, the electron Monte Carlo module offered in the XiO
treatment planning system is promising and could greatly improve the accuracy of
clinical dose calculations. The validation of the software is ongoing, notably
concerning more complex phantom geometries. Small field calculations, oblique
incidences and cutout factors will also be investigated.
PMID- 28516554
TI - Sci-Thur PM: YIS - 01: Inverse treatment planning for modulated electrons and
mixed photon and electron radiotherapy.
AB - Modulated electron radiotherapy (MERT) takes advantage of the low distal dose of
electrons to reduce dose to healthy tissue. The dosimetric advantage of MERT is
clear when compared against single-field electron irradiation where MERT
demonstrates superior target homogeneity and sparing; however the dosimetric
advantage is unclear when comparing MERT with photon intensity-modulated
radiotherapy (IMRT) where MERT techniques struggle to match the IMRT target
homogeneity but with less total energy delivered to healthy tissues. In an effort
to improve dosimetric benefits of MERT, this study investigated an inverse
planning technique for the creation of hybrid MERT-IMRT mixed beam radiotherapy
(MBRT) plans. The optimization process decouples the photon and electron beamlets
for combined modality optimization. The input to the optimization algorithm was a
series of patient-specific 3D dose distributions for the corresponding electron
and photon beamlets, while the output was a list of weights that satisfied the
optimization constraints. A photon IMRT Eclipse (Varian, Palo Alto, CA) plan and
a MERT plan were created for a patient-specific sarcoma irradiation. The MERT
plan was competitive in its ability to reduce dose to organs at risk and total
body dose; however, the plan suffered from poorer target conformity compared with
the IMRT plan. The MBRT plan was created by adding two photon fields, divided
into beamlets, to the electron beamlets of the MERT plan for reoptimization. The
MBRT plan improved MERT target coverage with only minimal cost to healthy tissue
dose. The MBRT plan provided clear dosimetric advantages over the IMRT and MERT
plan.
PMID- 28516556
TI - Erratum: "Enhanced dosimetry procedures and assessment for EBT2 radiochromic
media" [Med. Phys. 39(4), pp. 2147-2155 (2012)].
PMID- 28516557
TI - Sci-Thur PM: YIS - 04: Forcing lateral electron disequilibrium to spare lung
tissue: A novel technique for SBRT of small lung tumours.
AB - Stereotactic body radiation therapy(SBRT), a technique that uses tightly
conformed Megavoltage(MV) x-ray fields, improves local control of lung cancer.
However, small MV x-ray fields can cause lateral electron disequilibrium(LED),
which reduces the dose within lung. These effects are difficult to predict and
are presently a cause of alarm for the radiotherapy community. Previously, we
developed The Relative Depth Dose Factor(RDDF), which is an indicator of the
extent of LED (RDDF < 1). We propose a positive application of LED for lung
sparing in SBRT: LED can be exploited to irradiate a small tumor while greatly
reducing the dose in surrounding lung tissue. The Monte Carlo code, DOSXYZnrc,
was employed to calculate dose within a cylindrical lung phantom. The phantom's
diameter and height were set to 25 cm, and consisted of water and lung (density =
0.25g/cm3 ) shells surrounding a small water tumor (volume = 0.8 cm3 ). Two 180
degrees 6MV arcs were focused onto the tumor with field sizes of 1*1cm2
(RDDF~0.5) and 3*3cm2 (RDDF~1). Analyzing dose results, the 1*1cm2 arc reduced
dose within lung and water tissues by 70% and 80% compared to the 3*3cm2 arc.
Although, central tumor dose was also reduced by 15% using the 1*1cm2 arc, these
reductions can be offset by escalating the prescription dose appropriately. Using
the RDDF as a guideline, it's possible to design a SBRT treatment plan that
reduces lung dose while maintaining relatively high tumor dose levels. Clinical
application requires an accurate dose algorithm and may lower SBRT dose-induced
toxicity levels in patients.
PMID- 28516558
TI - Poster - Thur Eve - 05: Safety systems and failure modes and effects analysis for
a magnetic resonance image guided radiation therapy system.
AB - INTRODUCTION: An online Magnetic Resonance guided Radiation Therapy (MRgRT)
system is under development. The system is comprised of an MRI with the
capability of travel between and into HDR brachytherapy and external beam
radiation therapy vaults. The system will provide on-line MR images immediately
prior to radiation therapy. The MR images will be registered to a planning image
and used for image guidance. With the intention of system safety we have
performed a failure modes and effects analysis. METHODS: A process tree of the
facility function was developed. Using the process tree as well as an initial
design of the facility as guidelines possible failure modes were identified, for
each of these failure modes root causes were identified. For each possible
failure the assignment of severity, detectability and occurrence scores was
performed. Finally suggestions were developed to reduce the possibility of an
event. RESULTS/DISCUSSION: The process tree consists of nine main inputs and each
of these main inputs consisted of 5 - 10 sub inputs and tertiary inputs were also
defined. The process tree ensures that the overall safety of the system has been
considered. Several possible failure modes were identified and were relevant to
the design, construction, commissioning and operating phases of the facility. The
utility of the analysis can be seen in that it has spawned projects prior to
installation and has lead to suggestions in the design of the facility.
PMID- 28516559
TI - Poster - Thur Eve - 15: Production and assessment of astatine-211 for targeted
alpha therapy.
AB - Biologically-targeted alpha-particle radiation is the basis of new and promising
treatments for eliminating disseminated micrometastases and the residual
microscopic malignancies that remain after surgery or radiation therapy. The
short-range alpha-particles are highly cytotoxic and capable of inactivating
single, isolated cancer cells which may otherwise cause recurrence. Astatine-211
is a promising alpha emitter for therapy; the 7.2 hour half-life of 211 At
provides sufficient time for biological-targeting to take place. However, this
radionuclide is in short supply and future treatment strategies still require
extensive preclinical evaluation. The present work aims to develop technologies
that (1) increase the world-wide availability of 211 At for clinical use, and (2)
assess the risks of 211 At-based therapies by quantifying the activity
distributions in animal models. At TRIUMF (Vancouver, BC), the feasibility of a
novel generator system for 211 At is under investigation which would allow
distribution of 211 At across Canada and internationally. Briefly, a longer-lived
parent radionuclide of 211 At, radon-211, would be produced and allowed to decay
in containment to yield 211 At in solution. Additionally, a supplementary study
is underway in collaboration with the University of Washington to evaluate the
sub-organ biodistributions of astatinated targeting biomolecules, with cell-level
resolution. These measurements involve high resolution quantitative alpha
particle imaging in thin tissue samples and can be done for a selection of
applications (eg. lymphoma, metastatic prostate cancer, etc) using animal models.
The planned alpha-camera measurements are primarily designed to predict and
assess the risk of toxicity associated with 211 At-based therapies and aid in
developing the future clinical applications.
PMID- 28516560
TI - Sci-Thur PM: YIS - 08: The effect of copper conversion plates on low-Z target
image quality.
AB - Current generation electronic portal imaging devices (EPID) contain a 1.0 mm
copper conversion plate to increase detection efficiency of a therapeutic
megavoltage spectrum. When using these EPIDs for low-Z target imaging, the
conversion plate largely attenuates the large populations of diagnostic energy
photons, thereby decreasing the benefits of low-Z target imaging. In this work we
measure directly the effect the variation in thickness of a copper conversion
plate has on image quality in planar and cone beam computed tomography imaging.
Monte Carlo modeling was used to quantify changes to the diagnostic spectrum and
detector response for low-Z target beams generated with 2.35 and 7.00 MeV
electrons incident on a carbon target. Planar contrast-to-noise ratio (CNR)
measurements were made as a function of copper thickness. Cone beam computed
tomography (CBCT) image CNR measurements were made as a function of dose both
with and without the copper plate present in the EPID. The presence of copper in
the EPID decreased the diagnostic photon population by up to 20% and suppressed
the peak detector response at 60 kV by a factor of 6.4. Planar CNR was increased
by a factor ranging from 1.4 to 4.0 with no copper present compared to 1.0 mm
thickness. Increases in CBCT image CNR ranged from a factor of 1.3 to 2.1 with
the copper plate removed. As a result of this we suggest that the copper
conversion plate be removed from the EPID when used for low-Z target planar or
CBCT imaging.
PMID- 28516561
TI - Poster - Thur Eve - 08: A1SL ion chamber charged particle disequilibrium
corrections for lung dose measurements using Monte Carlo.
AB - An in house inhomogeneous insert for use with ArcCHECK TM was developed for dose
calculation verification of Stereotactic Body Radiation Therapy (SBRT) lung
plans. The inhomogeneous insert has various ion chamber inserts for different
geometrical configurations (lung, soft tissue, bone, air). However, the insertion
of an ion chamber in a low density medium perturbs the dose to that region by
creating Charged Particle Disequilibrium (CPD), limiting the accuracy of ion
chamber measurements. By simulating the ion chamber and phantom using Monte
Carlo, a correction factor could be calculated and measured to verify the dose
difference caused by CPD. BEAMnrc was used to generate a phase space input file
for DOSXYZnrc with beam characteristics that matched clinical commissioning data.
A model of the A1SL ion chamber geometry (shell, collector, stem, guard) was
simulated in a simple water-lung-water slab phantom. Dose to the active area of
the ion chamber was measured in several locations throughout the phantom. The
active area of the ion chamber was replaced by the surrounding medium; i.e.,
water or lung within the phantom, and the dose to the same voxels was calculated.
The dose was measured on a Linac and the results agreed within 3% and confirmed
that the presence of the ion chamber in low density lung perturbs the dose
measured in the field by over 31%.
PMID- 28516562
TI - Sci-Thur AM: Planning - 08: Validation of a commercial Monte Carlo code used for
stereotactic radiosurgery and stereotactic body radiation therapy.
AB - Our project consisted of validating the BrainLab iPlan Monte Carlo algorithm,
used in conjunction with the stereotactic radiosurgery (SRS) mode of the Varian
Novalis TX linear accelerator, for clinical use. Our approach was to "benchmark"
the iPlan algorithm by comparing dose distributions with those obtained using a
BEAMnrc model of the Novalis SRS mode. The BEAMnrc model was obtained by
modifying an existing accelerator model to include the SRS flattening filter and
source characteristics of the Novalis TX, and by reprogramming a component module
to model the high definition 120-leaf multi-leaf collimator. The free parameters
of interleaf air gap and leaf density were adjusted by matching to interleaf
leakage profiles measured with EBT2 film. The BEAMnrc model was used to perform
comparisons of depth dose curves and planar distributions for fields in
homogeneous and heterogeneous slab phantoms between both MC codes and film. The
source parameters of electron beam energy, size and angular spread were
determined to be 6.6 MeV, 0.7 mm and 0.8 mm (cross and in-plane), and 1.27
degrees , respectively. Comparisons between iPlan and EGSnrc MC codes show
agreement within 2% for PDD curves, and a high pass rate (>98%) on gamma analysis
(3%/3mm) for planar distributions, when the scored quantity is dose to medium.
Discrepancies between both MC codes and film measurements were seen near bone
inhomogeneities, where the film trend agrees somewhat with iPlan MC reporting
dose-to-water. Further work is being performed to understand these differences
and how film is used to measure dose near bone.
PMID- 28516563
TI - Reply to "Comment on the 'Report of AAPM TG 204: Size-specific dose estimates
(SSDE) in pediatric and adult body CT examinations'" [AAPM Report 204, 2011].
PMID- 28516564
TI - Poster - Thur Eve - 02: Regulatory oversight of the robotic radiosurgery
facilities.
AB - Following a recent review of the Class II Nuclear Facilities and Prescribed
Equipment Regulations and regulatory oversight of particle accelerators, the
Canadian Nuclear Safety Commission (CNSC) has changed its policy concerning the
regulation of particle accelerators. In November 2011, the CNSC began to exercise
its regulatory authority with respect to all particle accelerators operating at a
beam energy of 1 (one) MeV or greater. The CNSC already licences and inspects
particle accelerators capable of operating at or above 10 MeV. The decision to
now include low energy particle accelerators (i.e., those operating at or above 1
MeV) ensures adequate, uniform and consistent regulatory oversight for all Class
II accelerators. The CNSC expects these facilities to comply with CNSC
requirements by December 2013. Besides conventional linear accelerators of lower
energy (6 MeV or below) typically found in cancer clinics, two types of equipment
now fall under the CNSC's regulatory oversight as a result of the above change:
robotic radiosurgery and tomotherapy equipment and facilities. A number of
clinics in Canada already operates these types of equipment and facilities. The
safety aspects of radiosurgery equipment differ slightly from those for
conventional linear accelerators. This poster aims to present an approach taken
by the CNSC to regulate robotic radiosurgery equipment and facilities. The
presentation will explain how to meet regulatory requirements of the Class II
Nuclear Facilities and Prescribed Equipment Regulations by licensees operating or
planning to acquire these types of equipment and facilities.
PMID- 28516565
TI - Sci-Thur AM: Planning - 01: Experimental and Monte Carlo verification of Acuros
XB calculations near low and high density heterogeneities.
AB - The purpose of this study was to examine the accuracy of AcurosXB and AAA
algorithms near low and high density heterogeneities of different densities using
EBT2 film, MOSFET detector "MOSkin" and Monte Carlo calculations using
BEAMnrc/DOSXYZnrc. Three different interfaces were used that included a solid
water phantom with 2*2*30cm3 rectangular air gap, rectangular steel insert, and a
slab of water embedded between two slabs of lung material. 6MV photon beam with
field size of 10*10cm2 was used for the first two geometries and a 3*3cm2 -field
was used for the third. Percentage Depth Doses were measured and calculated at
the beam central axis. Calculation voxel of 0.1*0.1*0.1cm3 was used by all three
algorithms. For all configurations, AcurosXB and AAA agreed to within +/-1.3%
with MC before the inhomogeneity. The PDD measurements using MOSkin and EBT2 in
water, apart from 0.2cm layer near heterogeneity, agreed with the MC within +/
2.2%. Within 0.1cm before the water-air interface AcurosXB and AAA overestimated
the dose by 4.7% and 1.6%, respectively. Whereas, in the 0.1cm beyond the air
water interface, AcurosXB and AAA overestimated the dose by 2.4% and 16.2%
respectively. In the 0.1cm before the water-steel interface, AcurosXB
overestimated the dose by 4.7% and AAA underestimated the dose by 9.5%; beyond
the steel-water interface AcurosXB and AAA overestimated the dose by 3.6% and
7.7% respectively. For the lung phantom configuration, AcurosXB and AAA were in
agreement with MC within 2% throughout the phantom. These results demonstrate
improved performance of AcurosXB as compared to AAA in considered conditions.
PMID- 28516566
TI - Sci-Thur AM: Planning - 12: Comparative study of SBRT lung dose calculation using
Eclipse and Monte Carlo.
AB - Stereotactic Body Radiation Therapy (SBRT) is an option for early stage non-small
cell lung cancer treatment. In SBRT treatment, high biological effective dose is
delivered to the patient within a small number of fractions. High level of
confidence in accuracy is required in the entire treatment procedure, from
patient setup, tumour delineation, treatment simulation and planning, to the
final dose delivery. SBRT lung treatment utilizes small fields that are incident
on large tissue inhomogeneities within the patient. It is difficult for
commercially available treatment planning systems (TPS) to model the lack of
charged particle equilibrium and the dose near tissue-lung interfaces accurately.
The Monte Carlo (MC) technique calculates the dose distribution from the first
principles thereby providing a feasible tool for verifying the dose distribution
computed from TPS. In this study, we compared the SBRT dose distribution between
Eclipse 8.9 and BEAMnrc/DOSXYZnrc for both conformal and RapidArc plans.
Calculation results for five clinical SBRT conformal lung plans were compared.
Eclipse and MC results for each plan showed good agreement in dose received by
organs at risk. MC simulation predicted uniformly hotter or similar PTV coverage
for three cases with tumor either small or attached to the chest wall. When tumor
is inside lung and at relatively medium to larger size for SBRT, MC predicted
lower PTV coverage. The variation in dose coverage may depend on the tumour size
and its position within the lung. Dose comparison for RapidArc plans shows
similar dependence.
PMID- 28516568
TI - Sci-Thur PM: YIS - 03: Comparing 4D-VMAT, Gated-VMAT and 3D-VMAT in SBRT
treatment of lung cancer.
AB - PURPOSE: To evaluate the treatment plan qualities of 4D-VMAT, gated-VMAT and 3D
VMAT in the treatment of non-small cell lung cancer (NSCLC) in stereotactic body
radiation therapy (SBRT). METHODS: 4D-VMAT is a motion compensation strategy that
aims to exploit relative target and OAR motion to increase OAR sparing over 3D
VMAT without the long treatment times associated with gated-VMAT. The 4D-VMAT
algorithm incorporates the entire patient respiratory cycle and 4D-CT in the
optimization process. Resulting treatment plans synchronize the delivery of each
MLC aperture to a specific phase of the target motion. Using software developed
in MatlabTM, SBRT treatment plans for 4D-VMAT, gated-VMAT and 3D-VMAT were
generated on 3 patients with NSCLC. Tumour motion ranged from 1.4-3.4 cm. The
fractionation scheme was 48Gy in 4 fractions with the GTV receiving 100% of the
prescribed dose. For gated-VMAT, the treatment window constrained residual tumour
motion to 3 mm or less corresponding to duty cycles of 40-60%. In 3D-VMAT, the
ITV was generated by merging the GTV from all phases. A b-spline transformation
model was used to register the 4D-CT images and DVHs were calculated from total
dose accumulated on the max expiration phase. RESULTS AND CONCLUSION: For the
majority of OARs, gated-VMAT provided the greatest radiation sparing but
significantly extended treatment times (25-35 gantry interruptions/arc). For 3D
VMAT, only 2 patients had clinically acceptable plans that met all the strict
dose limits. OAR sparing in 4D-VMAT was comparable to gated-VMAT but with
significantly improved delivery efficiency.
PMID- 28516569
TI - STAT4 expression and activation is increased during mitosis in vitro and in vivo
in skin- and mucosa-derived cell types: implications in neoplastic and
inflammatory skin diseases.
AB - BACKGROUND: The signal transducer and activator of transcription-4 (STAT4/Stat4)
is a transcription factor known to convey signals from interleukin-12,
interleukin-23, and interferon-alpha/beta to the nucleus, resulting in activation
of dendritic cells, T-helper cell differentiation and production of interferon
gamma. OBJECTIVE: To demonstrate a novel role for STAT4 in cell mitosis. RESULTS:
Phosphoserine STAT4 (pSerSTAT4) is increased in cells undergoing mitosis and is
distributed throughout the cytoplasm during this stage of the cell cycle, whilst
phosphotyrosine STAT4 (pTyrSTAT4) is confined to the chromosomal compartment.
This distinct pattern of pSerSTAT4 during mitosis is seen in vitro in human
keratinocytes and in other cell types. This is also present in vivo in cells
undergoing mitosis in normal skin, psoriasis and squamous cell carcinoma.
Inhibition of STAT4 phosphorylation by lisofylline and depletion of STAT4 by RNA
interference results in a delay in progression of mitosis and leads to a
reduction in cells completing cytokinesis. CONCLUSION: Our data demonstrate that
STAT4 plays a role in enabling the normal and timely division of cells undergoing
mitosis.
PMID- 28516570
TI - Proposal of size-based surgical indication criteria for liver hemangioma based on
a nationwide survey in Japan.
AB - BACKGROUND: Surgical indications for liver hemangioma remain unclear. METHODS: Of
510 patients undergoing surgical resection for liver hemangioma in 118 Japanese
centers between 1998 and 2012, abdominal symptoms, diagnostic accuracy, and
surgical outcomes were analyzed to propose size-based surgical indications.
Patients were classified into four groups based on tumor size: Group A <=5 cm (n
= 122, 24%), Group B 5-10 cm (n = 164, 32%), Group C 10-15 cm (n = 124, 24%), and
Group D >15 cm (n = 100, 20%). RESULTS: Hemangiomas in Group A were most
frequently diagnosed as malignant tumors (43.5%) due to the absence of typical
imaging findings and with highest incidence of positive HBV (15.7%). Diagnostic
accuracy was 98.4% in Groups B to D. Liver failure after hepatectomy was higher
in Group D than in Groups A to C (3.0% vs. 0.5%, P = 0.02). Only one operative
death was observed (0.2%) in Group D. CONCLUSIONS: In patients with <=5 cm
hemangioma, surgical resection can be indicated when a malignant tumor cannot be
ruled out. However, surgery for 5-10 cm asymptomatic hemangiomas should be
limited. Experienced hepatic surgeons should conduct hepatectomy for tumors >15
cm to avoid serious morbidity or mortality.
PMID- 28516622
TI - Abstracts of the XVII GISMAD Congress, Milan, Italy, 9-11 March 2017.
PMID- 28516572
TI - Identification of ageing biomarkers in human dermis biopsies by thermal analysis
(DSC) combined with Fourier transform infrared spectroscopy (FTIR/ATR).
AB - BACKGROUND/PURPOSE: The purpose of this clinical study was to identify suitable
biomarkers for a better understanding of the molecular and organizational changes
in human dermis during intrinsic and extrinsic ageing. METHODS: Sun-exposed and
non-exposed skin biopsies were collected from twenty-eight women devised in two
groups (20-30 and >=60 years old). The hydric organization and thermal
transitions were determined by Differential Scanning Calorimetry (DSC). Fourier
Transform Infrared spectroscopy (FTIR) was used to identify the absorption bands
of the dermis and to quantify the different absorbance ratio. RESULTS: The
amounts of total, freezable and unfreezable water were determined. A significant
increasing amount of freezable water is evidenced in sun-exposed area skin of
aged group compared with young group (P=.0126). Another significant effect of
extrinsic ageing (P=.0489) is the drastic decrease of fibrillary collagen, the
main protein component of dermis. The only significant effect of intrinsic ageing
(P=.0184) is an increase of the heat-stable fraction of collagens in dermis.
CONCLUSION: DSC and FTIR are well-suited techniques to characterize human skin,
giving accurate results with a high reproducibility. The combination of these
techniques is useful for a better understanding of human skin modifications with
intrinsic and extrinsic ageing.
PMID- 28516571
TI - FSOCA-induced switchable footpad skin optical clearing window for blood flow and
cell imaging in vivo.
AB - The mouse footpad for its feature of hairlessness provides an available window
for imaging vascular and cellular structure and function in vivo. Unfortunately,
the strong scattering of its skin limits the penetration of light and reduces the
imaging contrast and depth. Herein, an innovative footpad skin optical clearing
agent (FSOCA) was developed to make the footpad skin transparent quickly by
topical application. The results demonstrate that FSOCA treatment not only
allowed the cutaneous blood vessels and blood flow distribution to be monitored
by laser speckle contrast imaging technique with higher contrast, but also
permitted the fluorescent cells to be imaged by laser scanning confocal
microscopy with higher fluorescence signal intensity and larger imaging depth. In
addition, the physiological saline-treatment could make the footpad skin recover
to the initial turbid status, and reclearing would not induce any adverse effects
on the distributions and morphologies of blood vessels and cells, which
demonstrated a safe and switchable window for biomedical imaging. This switchable
footpad skin optical clearing window will be significant for studying blood flow
dynamics and cellular immune function in vivo in some vascular and immunological
diseases. Picture: Repeated cell imaging in vivo before (a) and after (b) FSOCA
treatment. (c) Merged images of 4 h (cyan border) or 72 h (magenta border) over 0
h. (d) Zoom of ROI in 4 h (yellow rectangle) or 72 h (red rectangle).
PMID- 28516623
TI - Sci-Sat AM: Brachy - 05: Comprehensive web-based QA in radiation oncology.
AB - Innovation/Impact: We describe the web-based QA infrastructure under development
and in use within our paperless radiation oncology clinic. Our framework
comprises a centralized web-server that facilitates simultaneous and seamless
access to multiple databases within the clinic. All activities, including
treatment planning, patient appointments and machine quality control/maintenance,
are accessible via a single internal webpage with various software tools and
metrics employed for QA and monitoring. We believe that our framework is
representative of the direction in which modern radiation oncology departments
are moving; namely paperless operation with centralized data access for patient
specific QA and statistical process control.
PMID- 28516624
TI - Sci-Fri PM: Delivery - 10: Megavoltage x-ray imaging detector based on cerenkov
effect.
AB - A Monte Carlo simulation was used to study imaging and dosimetric characteristics
of a novel design of a megavoltage (MV) x-ray imaging detector. The proposed
detector consists of a matrix of optical fibers aligned with the incident x-rays
and coupled to an active matrix flat-panel imager (AMFPI) for image readout. The
new design relies on Cerenkov effect for MV x-ray imaging and is named CPID (for
Cerenkov Portal Imaging Device). When MV x-rays are incident on CPID, they
interact within the volume of the detector primarily via Compton effect and pair
production, resulting in electrons and positrons. From these charged particles,
those with sufficient energy, trigger production of optical light via Cerenkov
effect. The light that is generated in the optical fibre cores within the
acceptance angle of the fibers is guided towards the AMFPI. Properties, such as
detection efficiency, modulation transfer function, zero frequency detective
quantum efficiency (DQE), and energy response of the detector, have been
investigated. It has been shown that the proposed detector can have a zero
frequency DQE more than an order of magnitude higher than that of current
electronic portal imaging device (EPID) systems and yet a spatial resolution
comparable to that of video-based EPIDs. In additional the proposed detector is
less sensitive to scattered x-rays than current EPIDs.
PMID- 28516625
TI - Sci-Sat AM: Brachy - 09: Permanent seed re-implantation using image guidance for
composite dose planning.
AB - Treatment outcome has been associated with dosimetric implant quality assessed in
a postplan. Uncertainties during the implant and in the period before postplan
evaluation lead to dosimetric deviations from the original treatment plan. The
observed range of postplan results can include patients with dosimetry below
recommended levels. Further treatment options may be considered to boost the
delivered dose and a second seed implant is one way to accomplish this. This work
describes the development of a procedure to plan and deliver a second seed
implant and an evaluation of the dosimetric improvement. A patient with a post
plan D90 of 124 Gy was offered a second seed implant 21 weeks after the initial
implant. A total dose of 163 Gy was prescribed due to radiobiological
considerations for the time between implants. A volume study was performed 2
weeks before the implant and variable angle images of the seeds from the first
implant were obtained to reconstruct the original seed coordinates. The second
implant was planned considering the total composite physical dose distribution by
forward planning additional seeds onto the original implant coordinates. The
additional seeds were manually added to a new plan on the volume study images at
the planned coordinates and delivered as a typical preplanned implant. Post-plan
evaluation four weeks after the second implant showed a D90 of 177 Gy and a V100
of 92.7%. These results demonstrate the effective use of a second seed implant
with image guided composite planning to improve dosimetric implant quality.
PMID- 28516626
TI - Poster - Thur Eve - 73: Prediction of risks of cardiac mortality and secondary
cancers after radiotherapy for Hodgkin's lymphoma, non-Hodgkin's lymphoma, and
breast cancer.
AB - PURPOSE: To predict the risks of late, radiation-induced effects for young
patients with Hodgkin's lymphoma (HL), non-Hodgkin's lymphoma (NHL), or breast
cancer (BC) if treated with intensity modulated proton therapy (IMPT) compared to
3D conformal photon radiotherapy (3D-CRT). Late effects considered were cardiac
mortality and secondary cancer in the lungs and breasts (for female patients).
METHODS: Patient data were acquired for twenty-six patients (ages 12-29) who were
treated with 3D-CRT for HL, NHL, or BC in 2010. Original CT simulation images
were used to re-plan the patients with IMPT using commercially-available
treatment planning software. The contours of the organs at risk were reviewed by
a single physician and modified for consistency. The dose-volume data of the 3D
CRT plans and the new IMPT plans were analyzed to model the risks of late
effects. The relative seriality model was used to predict excess risk of cardiac
mortality at fifteen years post-irradiation. A modified linear quadratic model
was used to predict the Excess Absolute Risk (EAR) for induction of lung cancer
and breast cancer at thirty years post-irradiation. RESULTS: For 3D-CRT and IMPT
respectively, the mean excess risks of cardiac mortality were 0.9% and 0.5%. Mean
EARs for lung cancer were 17.5 cases per 10,000 persons per year (PY) and 10.1
PY. Mean EARs for breast cancer were 8.2 PY and 2.8 PY. CONCLUSIONS: IMPT may
significantly reduce the risks of radiation-induced cardiac mortality and
secondary cancer in the lungs and breasts of young patients receiving
radiotherapy for HL, NHL, or breast cancer.
PMID- 28516627
TI - Sci-Fri AM: Imaging - 07: Symmetric geometric transfer matrix partial volume
correction technique for emission tomography: Principle, validation, and
robustness.
AB - Partial volume correction (PVC) is often needed to correct for limited spatial
resolution in quantitative Positron Emission Tomography (PET) and Single Photon
Emission Computed Tomography (SPECT) studies. In conventional region-based PVC
methods, spill over between regions segmented from coregistered computed
tomography (CT) or magnetic resonance (MR) images is accounted for by calculating
regional spread functions (RSFs) in a geometric transfer matrix (GTM) framework.
This paper describes a new analytically derived symmetric GTM (sGTM) method that
considers spill over between RSFs rather than between regions. The sGTM is
mathematically equivalent to Labbe's method, however it is region-based rather
than voxel-based and it avoids handling large matrices. The sGTM method was
validated using an MR-based 3D digital brain phantom and a physical phantom
containing spheres 5 mm to 30 mm in diameter. The sGTM method was compared to the
GTM method in terms of accuracy, precision, noise propagation, and robustness,
i.e. effects of mis-registration or point spread function (PSF) estimation
errors. The results showed that the sGTM method has accuracy similar to that of
the GTM method, and within 5% of the true value. However, the sGTM method showed
better precision and noise propagation than the GTM method, especially for
spheres smaller than 13 mm. Moreover, the sGTM method was more robust than the
GTM method when misregistration or errors in estimates of PSF occurred. In
conclusion, the sGTM method was analytically derived and validated and shown to
exhibit better noise characteristics and robustness compared to the GTM method.
PMID- 28516628
TI - Sci-Sat AM: Brachy - 02: Extracting Wair from the 1976 electron beam measurements
of domen and lamperti.
AB - The average energy expended by an energetic electron to create an ion pair in
air, Wair is an important quantity in radiation dosimetry. The data obtained by
Domen and Lamperti using electron beams in the energy range from 15 to 50 MeV can
be used to extract a value for Wair if the electron stopping powers of graphite
and air are assumed to be known. We use Monte Carlo techniques to reanalyze these
data and obtain a new estimate for the value of Wair Using the EGSnrc Monte Carlo
and its associated user codes, as well as the best availabl-e stopping power data
for graphite, we calculate the perturbation effects due to the calorimeter and
ionization chamber and the effect of extrapolating from scattered to plane
parallel beams. Without further adjustments, the extracted values of Wair show a
significant trend as the mean electron energy decreases. We show that part of
this trend can be attributed to an incorrect value of the density assigned to the
graphite absorbers and part to the likelihood that the nominal energy assigned to
the low-energy electron beams is not correct. Using all the data, we obtain a
value for Wair of 33.84 eV per ion pair with a relative standard uncertainty of
0.4 %. This result serves to complement values obtained using 60 Co gamma-rays,
for which the value of the mean excitation of graphite contributes significantly
to the uncertainty.
PMID- 28516629
TI - Poster - Thur Eve - 67: Clinical results of deep inspiration breath hold
radiation treatment for the left breast patients.
AB - Adjuvant radiotherapy for left breast cancers increases local tumor control, but
also increases the risk of radiation-induced cardiac disease. Deep Inspiration
Breath Hold (DIBH) can minimize dose to the heart for left breast patients where
the heart is within the tangential field. In this study, we evaluated the
dosimetric benefit of DIBH technique comparing to free breathing (FB)
radiotherapy for left breast cancer patients. Five patients with left breast
cancer treated with DIBH technique were selected randomly. The CT scans of breath
hold (BH) and FB were taken for every DIBH patient. Standard clinical DIBH
intensity-modulated radiotherapy (IMRT) plans were generated with BH scan dataset
using the Varian Eclipse TP system. The prescription dose is 4250 cGy in 16
fractions. The BH plan was copied to the FB scan dataset and shifted accordingly
to have the same coverage for the breast tissue, and the dose was re-calculated.
Dose-volume histograms (DVH) of the heart and lung; mean dose and maximum dose of
the heart were calculated and compared from the BH and FB plans for every
patient. The lung volume is increased during BH and hence the heart is moved out
of the field, resulting in the lower heart maximum dose. The mean dose is almost
less than 1 Gy for all BH plans. The average mean heart dose is 0.8 Gy for BH
plan compared to 1.6 Gy for FB plan. Patients benefit significantly from DIBH
technique due to the very low heart dose.
PMID- 28516630
TI - Poster - Thur Eve - 77: Coordinate transformation from DICOM to DOSXYZnrc.
AB - DICOM format is the de facto standard for communications between therapeutic and
diagnostic modalities. A plan generated by a treatment planning system (TPS) is
often exported to DICOM format. BEAMnrc/DOSXYZnrc is a widely used Monte Carlo
(MC) package for beam and dose simulations in radiotherapy. It has its own
definition for beam orientation, which is not in compliance with the one defined
in DICOM standard. Dose simulations using TPS generated plans require
transformation of beam orientations to DOSXYZnrc coordinate system (c.s.) after
extracting the necessary parameters from DICOM RP files. The transformation is
nontrivial. There have been two studies for the coordinate transformations. The
transformation equation sets derived have been helpful to BEAMnrc/DOSXYZnrc
users. However, both the transformation equation sets are complex mathematically
and not easy to program. In this study, we derive a new set of transformation
equations, which are more compact, better understandable, and easier for
computational implementation. The derivation of polar angle theta and azimuthal
angle phi is similar to the existing studies by applying a series of rotations to
a vector in DICOM patient c.s. The derivation of beam rotation Phicol for
DOSXYZnrc, however, is different. It is obtained by a direct combination of the
actual collimator rotation with the projection of the couch rotation to the
collimator rotating plane. Verification of the transformation has been performed
using clinical plans created with Eclipse. The comparison between Eclipse and MC
results show exact geometrical agreement for field placements, together with good
agreement in dose distributions.
PMID- 28516631
TI - Sci-Fri PM: Delivery - 02: CT image guidance strategies for dose-adaptive IMRT of
the prostate.
AB - On-line CT imaging in the radiotherapy room has become the norm for targeted
intensity-modulated radiotherapy (IMRT), enabling precise adjustments of the
daily patient setup based on soft tissue visualization. Corrections for
plasticity of the anatomy and dose deformation are within technological reach but
will require more on-line resources. We have developed a computer model that
allows exploration of "what if" scenarios for assessing the benefits of Image
Guidance strategies in terms of the multi-fraction dose distribution and DVH
metrics (Target D95 and rectum V70). In this work we report on changes in anatomy
and resultant dose distribution as observed in 35 daily megavoltage CT (MVCT)
scans of the pelvis during prostate therapy for 13 patients. Our goal is to
assess the effectiveness and efficiency of various adaptive strategies involving
imaging schedule with and without dose re-planning of 5-field IMRT with 18 MV x
rays. Our research questions are: To what extent do radiation dose distributions
delivered to individual patients (in vivo) diverge from the planned dose
distributions (in silico)? Is there a robust schedule of CT image guidance, with
or without dose re-planning that will mitigate discrepancies? For prostate IMRT,
we conclude that image guidance schedule can be relaxed when generous GTV margins
(10/7mm) are used. Tighter margins (isotropic 5 mm) reduce the dose to the rectum
as expected. However, daily re-planning may be required to maintain adequate
target coverage as planned when tighter margins are used.
PMID- 28516632
TI - Poster - Thur Eve - 70: Quantification of tumour dose enhancement at kilo-voltage
energies due to the presence of gold nanoparticles during radiation therapy:
EGSnrcMP Monte Carlo study.
AB - One of the greatest challenges in radiation therapy is the ability to deliver a
lethal dose of radiation to a tumour while sparing the surrounding normal
tissues. In theory, the dose delivered to a tumour during photon-based radiation
therapy can be enhanced by loading high atomic number (Z) materials into the
tumour, which results in greater photoelectric absorption and hence increased
photoelectron fluence within the tumour than in surrounding tissues. The EGSnrcMP
Monte Carlo code, together with DOSXYZnrc, a three-dimensional voxel dose
calculation module has been used to study the macroscopic dose enhancement factor
(MDEF) in a tumour infused with gold nanoparticles at the kilo-voltage energies.
We observed that gold nanoparticles infused in a tumour irradiated with kilo
voltage energies has the potential to enhance the tumour dose by a factor ranging
from 0.25 to about 5 depending on the mean energy of the beam and the
concentration of gold nanoparticles in the tumour. The increase in dose can be
attributed to the significant increase in the photoelectron fluence within the
tumour loaded with gold particles during the irradiation. Future studies will
involve the characterization of the MDEF at megavoltage energies.
PMID- 28516633
TI - Sci-Fri PM: Delivery - 05: A complete set of VMAT machine-specific QA tests using
EPID.
AB - During a VMAT (Volumetric Modulated Arc Therapy) radiation delivery, various
machine parameters (gantry position and speed, MLC leaves position, dose rate,
etc) have to be highly synchronized and coordinated. To ensure that all of the
machine components are effectively operating together requires unique machine
specific quality assurance (QA) tests. The purpose of this work is to describe a
complete set of VMAT machine-specific QA tests using Electronic Portal Imaging
Device (EPID). To address the need for VMAT machine-specific QA tests, Varian has
recommended 6 EPID-based tests for commissioning and QA of RapidArcTM capable
machines. Recent studies have identified that these Varian tests do not define a
complete set of tests needed for adequate commissioning and machine-specific QA
of RapidArc machines. The goal of this work is twofold: a) to report and discuss
the results of the original 6 Varian's EPID-based tests, and b) to extend the
original set by adding 2 more EPID-based tests, which results in a more complete
and comprehensive set of tests. We have demonstrated that the Varian EPID-based
QA tests can be used to verify that the synchronization of Dose Rate, Gantry
Speed and MLC Leaves speed is generally to within 1.5% during a RapidArc
delivery. Also, the gantry rotation does not have any significant effect on MLC
leaves positional accuracy during a RapidArc delivery. Finally, we have
introduced a new EPID-based QA test, which can be used to verify that the angular
accuracy of the gantry position during a RapidArc delivery is to within ~1
degree.
PMID- 28516634
TI - Sci-Sat AM: Brachy - 04: Neutron production around a radiation therapy linac
bunker - monte carlo simulations and physical measurements.
AB - Photoneutrons are a major component of the equivalent dose in the maze and near
the door of linac bunkers. Physical measurements and Monte Carlo (MC)
calculations of neutron dose are key for validating bunker design with respect to
health regulations. We attempted to use bubble detectors and a 3 He neutron
spectrometer to measure neutron equivalent dose and neutron spectra in the maze
and near the door of one of our bunkers. We also ran MC simulations with MCNP5 to
measure the neutron fluence in the same region. Using a point source of neutrons,
a Clinac 1800 linac operating at 10 MV was simulated and the fluence measured at
various locations of interest. We describe the challenges faced when measuring
dose with bubble detectors in the maze and the complexity of photoneutron
spectrometry with linacs operating in pulsed mode. Finally, we report on the
development of a userfriendly GUI for shielding calculations based on the NCRP
151 formalism.
PMID- 28516635
TI - Sci-Fri PM: Delivery - 09: Response of a tumor xenograft model to radiation
therapy using magnetic resonance spectroscopy.
AB - 9.4T 1 H magnetic resonance spectroscopy (MRS) was utilized to track the response
of mouse xenograft glioblastoma multiform (GBM) brain tumors to single fraction
radiation therapy. Six metabolites were analyzed with LCModel: alanine (Ala), myo
inositol (Ins), taurine (Tau), creatine and phosphocreatine (Cr + PCr), glutamine
and glutamate (Glu + Gln), and total choline (glycerophosphocholine +
phosphocholine) (GPC + PCh). 11 mice received 800 cGy of 200 kVp x-rays, 5 were
untreated controls. PRESS spectra (27 MUL volumes) were acquired at multiple time
points for treated and control animals. In treated animals, all metabolite :
water ratios decreased 3 days post-treatment, with further decreases at day 7,
and then increases at day 14 relative to the 7 day mark. Concentrations on day 7
relative to pre-treatment were as follows: 0.42 (Ala), 0.43 (Ins), 0.68 (Tau),
0.52 (GPC+PCh), 0.49 (Cr + PCr) and 0.78 (Glu + Gln). Metabolite ratios did not
correlate with tumor volume in control animals, suggesting a real therapeutic
response was observed. Our 1 H MRS data suggests that perturbations in the
metabolic signature of GBM cancers occur in response to irradiation. Such changes
in the metabolite : water concentration ratios could potentially be exploited for
the improvement of radiotherapy.
PMID- 28516636
TI - Sci-Sat AM: Brachy - 08: MRI-guided planning and maximum achievable HR-CTV doses
in cervix brachytherapy.
AB - PURPOSE: To present an institutional experience with MRI-based intracavitary
brachytherapy planning for cervix cancer treatments using the EMBRACE protocol
and to evaluate maximum HR-CTV doses that can be achieved when OAR (bladder,
rectum, and sigmoid) doses are allowed to equal GECESTRO recommended thresholds.
METHOD: Dose metrics from treatment plans for 20 patients created using MR images
(for contouring HR-CTV and OARs) fused with CT images (for applicator
reconstruction) are presented. Starting with a standard Manchester loading, plans
were manually optimized (MO) by adjusting dwell positions and times to obtain the
desired HR-CTV D90 target coverage of 35 Gy while limiting OAR doses to below
recommended tolerances. In addition, retrospective planning was done using: (i)
volume optimization (VO) to compare differences with MO in obtaining the desired
target coverage; and (ii) MO and VO techniques to get the highest possible HR-CTV
coverage by allowing OAR doses to equal tolerance values. The latter plans are
referred to as MAX plans. RESULTS AND CONCLUSIONS: 3D MRI-guided treatment
planning for cervix brachytherapy was shown to improve dose-volume coverage of
the target and OARs. MO could conform HR-CTV D90 to the prescribed dose similar
to the VO technique. Sigmoid was often the dose limiting structure. With respect
to the prescribed HR-CTV D90 dose of 35 Gy, MAX plans could increase the
prescribed dose by about 22% and 30% for MO and VO plans, respectively, without
exceeding OAR thresholds. Consequently, dose escalation for MRI-guided cervix
brachytherapy appears feasible should clinical circumstances warrant.
PMID- 28516637
TI - Poster - Thur Eve - 72: Conversion of helical tomotherapy plans into clinically
favourable step-and-shoot IMRT plans deliverable on a c-arm linac.
AB - The treatment planning software SharePlan is designed to convert dose
distributions generated by the TomoTherapy planning station into step-and-shoot
IMRT plans deliverable on a c-arm linear accelerator. Five anal canal patients
who were planned for TomoTherapy treatments were exported into a SharePlan system
and plans were generated for delivery on an Elekta Synergy unit. A total of 80
plans were generated for those five patients, with either seven, nine, eleven or
twenty-one gantry angles and different priorities between focusing on matching
either the target doses or healthy tissue sparing of the TomoTherapy plan. The
plans generated by SharePlan, while often not matching target coverage at
prescription, matched well the TomoTherapy coverage at 95% and 105% of the
prescription dose. Organ at risk dose, when heavily emphazied in the SharePlan
calculations matched or bettered the TomoTherapy dose due to the placement of the
beams and the sharper sup-inf fall off of the dose distribution on a linac. For
one of the patients, it was possible to produce a better DVH with SharePlan than
the original TomoTherapy plan for those reasons. The TomoTherapy plans boasted
significantly shorter delivery times than the plans generated with SharePlan.
PMID- 28516638
TI - Sci-Fri AM: Imaging - 06: The role of body mass and gender in atlas construction
for attenuation correction in PET/MRI.
AB - Attenuation correction (AC) in PET/MRI is difficult as there is no clear
relationship between MR signal and 511 keV attenuation coefficients (MU) as there
is with CT. One approach is to register a pre-defined atlas of MU to the PET/MRI
for AC. However, the design of the atlas may strongly influence the quantitative
accuracy of the AC. Here we compare 3 different atlas design approaches and
evaluate their performance in an oncology patient population. The 3 strategies
were: use of BMI-dependent atlases; use of gender-dependent atlases, and use of a
gender- and sex-independent atlas. Seventeen patients were imaged with FDG PET/CT
and subsequently scanned with 3T MRI. MR and PET/CT images were coregistered, CT
scans converted to MU-maps, and the resulting MRI/MU-map paired data were used to
construct 6 atlases: averaged male and female atlases, averaged BMI-specific
atlases (obese >30, overweight 25-29.9, Normal 18.5-24.9), and a single atlas
comprised of all patients averaged together. The atlases were then used for PET
AC for patients not included in the construction of the atlas in a leave-one-out
manner. Resulting PET images were compared to each other and to the gold-standard
CT-based PET reconstructions across all voxels and tissue-specific regions (soft
tissue, bone, lung). Sex-specific atlases yielded best results (average relative
percent error over the 3 VOIs = 0.4509) & BMI-based atlases yielded highest
average relative percent error at 0.9340. In all cases, highest errors were in
the VOIs located in the livers.
PMID- 28516639
TI - Sci-Sat AM: Brachy - 01: Evaluation of dose-volume metrics for microbeam
radiation therapy.
AB - Microbeam radiation therapy (MRT) is an experimental technique delivering an
array of high dose synchrotron X-ray microbeams. Development of metrics to
predict the biological efficacy of MRT dose distributions is needed to guide
further MRT research and for potential translation to human trials. The most
commonly used metric is the peak-to-valley-dose ratio (PVDR) relating the dose at
the microbeam center to that between two microbeams. We investigate three
additional metrics that characterize dose distributions from a more volumetric
perspective - the peak-to-mean-valley-dose ratio (PMVDR), mean dose, and
percentage volume below a threshold. The metrics are evaluated for Monte Carlo
simulations of dose distributions in three cubic head phantoms (2, 4 and 8 cm
side lengths) for microbeam widths of 25, 50, and 75 MUm and centre-to-centre
spacings of 100, 200 and 400 MUm. The ratio of the PMVDR to the PVDR varied from
0.24 to 0.80 for the different configurations, indicating a difference in the
predicted geometric dependence of outcome for these two metrics. The mean dose
was 102, 79, and 42 % of the mean skin dose for the 2, 8, and 16 cm head
phantoms, respectively. The percentage volume below a 10% dose threshold was
highly dependent on geometry, with ranges for the different collimation
configurations of 2 - 87% and 33 - 96% for the 2 and 16 cm heads, respectively.
Different dose-volume metrics exhibit different dependencies on MRT geometry
parameters, suggesting that reliance on PVDR as a predictor of therapeutic
outcome may be insufficient.
PMID- 28516640
TI - Poster - Thur Eve - 66: A planning comparison between RapidArc and intensity
modulated radiotherapy for head and neck cancer.
AB - Volumetric modulated arc therapy (VMAT) has recently been used to improve the
dose distribution and efficiency of treatment delivery over the standard
intensity-modulated radiotherapy (IMRT) technique. This study compares the
dosimetry between RapidArc plan and standard IMRT plan for head and neck cancer.
Three head and neck patients treated clinically with sliding window intensity
modulated radiotherapy (IMRT) technique at Grand River Regional Cancer Center
were selected randomly and re-planned using RapidArc technique with 6 MV photon
beams generated by a Varian 21EX linac with 120-leaf multileaf collimator. Three
dose prescriptions were used to deliver 70 Gy, 63 Gy and 58.1 Gy to the regions
of the primary tumors, intermediate-risk nodes and low-risk nodal level,
respectively, in 35 fractions. Dosimetric comparison based on the dose-volume
histogram, target coverage, organ at risk (OAR) dose sparing were studied between
the RapidArc plan and IMRT plan. RapidArc technique from Varian Medical Systems
showed superior target coverage, better OAR sparing, fewer monitor units per
fraction with less treatment time over IMRT technique for head and neck cancers.
The average homogeneity index, defined as the difference between the percentage
dose covering 5% and 95% of the PTV, is 9.5 for RapidArc plan and 10.5 for IMRT
plan. All RapidArc plans met the dose objectives for the primary OAR: spinal
cord, brainstem, brain etc. Both parotid mean dose and D50% are lower for
RapidArc plan than those of the IMRT plan. The technique is currently being used
clinically at our cancer center.
PMID- 28516641
TI - Sci-Sat AM: Brachy - 12: Resolving the olefinic lipid resonance from water in
proton magnetic resonance spectra of vertebral bone marrow at 3 T.
AB - Proton magnetic resonance spectroscopy (MRS) of vertebral lipids has been shown
to be relevant in the study of cancer. The olefinic resonance (~ 5.4 ppm) yields
a measure of lipid unsaturation. However, its measurement with standard short
echo time (TE) MRS sequences is difficult due to the large overlapping water
signal. The purpose of this work is to optimize the TE of a PRESS (Point RESolved
Spectroscopy) sequence to measure the olefinic resonance from spinal bone marrow
with minimal losses due to J-coupling and minimal contamination from water at 3
T, a field strength becoming more common in the clinic. Experiments were
conducted on nine oils and on L4 vertebral bone marrow in vivo at 3 T. The
methylene (or methyl + methylene), and olefinic resonances were measured with
PRESS using multiple TEs. The effects of J-coupling evolution of the olefinic
protons appeared to be minimal when TE = 200 ms. The TE = 200 ms
olefinic/methylene peak area ratios calculated for each oil correlated well with
ratios deduced from oil compositions in the literature (R2 = 0.92). The TE = 200
ms PRESS spectra obtained from vertebra of four volunteers showed negligible
contribution from water to the olefinic resonance, thereby enabling the olefinic
peak area to be quantified more accurately. The results of this work demonstrate
that a PRESS sequence with TE = 200 ms is suitable for measuring relative levels
of lipid unsaturation and for resolving the olefinic resonance from contaminating
water signal in spinal bone marrow.
PMID- 28516642
TI - Poster - Thur Eve - 76: A quality control to achieve planning consistency in arc
radiotherapy of the prostate.
AB - PURPOSE: To report a quality control program in prostate radiation therapy at our
center that includes semi-automated planning process to generate high quality
plans and in-house software to track plan quality in the subsequent clinical
application. MATERIAL AND METHODS: Arc planning in Eclipse v10.0 was preformed
for both intact prostate and post-prostatectomy treatments. The planning focuses
on DVH requirements and dose distributions being able to tolerate daily setup
variations. A modified structure set is used to standardize the optimization,
including short rectum and bladder in the fields to effectively tighten dose to
target and a rectum expansion with 1cm cropped from PTV to block dose and shape
posterior isodose lines. Structure, plan and optimization templates are used to
streamline plan generation. DVH files are exported from Eclipse to a quality
tracking software with GUI written in Matlab that can report the dose-volume data
either for an individual patient or over a patient population. RESULTS: For 100
intact prostate patients treated with 78Gy, rectal D50, D25, D15 and D5 are
30.1+/-6.2Gy, 50.6+/-7.9Gy, 65.9+/-6.0Gy and 76.6+/-1.4Gy respectively, well
below the limits 50Gy, 65Gy, 75Gy and 78Gy respectively. For prostate bed with
prescription of 66Gy, rectal D50 is 35.9+/-6.9Gy. In both sites, PTV is covered
by 95% prescription and the hotspots are less than 5%. CONCLUSION: The semi
automated planning method can efficiently create high quality plans while the
tracking software can monitor the feedback from clinical application. It is a
comprehensive and robust quality control program in radiation therapy.
PMID- 28516643
TI - Sci-Fri PM: Delivery - 01: Approach to evaluate the accuracy of individual
control-points of a VMAT delivery measured by an EPID.
AB - A unique approach that uses Monte Carlo (MC) methods to validate time-resolved
measured dose by an electronic portal imaging device (EPID) during delivery of
volumetric modulated arc therapy (VMAT) treatments was investigated. Time
resolved dose is simultaneously scored in both the patient and EPID geometries. A
RapidArc(c) verification plan was generated and delivered on a homogeneous
cylindrical phantom. Portal images were collected using an aS1000 amorphous
silicon EPID attached to a Varian Clinac 2100ix. The images were acquired in the
continuous acquisition mode and in-house analysis software was used to obtain
images for each control point. We performed MC simulation and dose calculation of
the verification plan using the EGSnrc MC package. The MC phantom file contains
both the EPID model and the cylindrical phantom derived from the CT data sets.
For the individual control point simulation, we rotate the phantom only using the
gantry angle information. For this work, we calculated dose distributions for
five control points (out of a total of 177) in the verification plan. The
normalized measured and calculated data were compared using the chi comparison
(computationally efficient implementation of gamma). The chi comparison between
measured and calculated doses for the five control points using criteria of 3%
and 3mm revealed an average of 88.7% of all pixels having chi<1. The agreement
will improve when the measured portal images are corrected for flood field and
support-arm backscatter effects. This approach allows us to obtain both the EPID
dose and the phantom/patient dose. These preliminary results demonstrate
promising accuracy. With further improvements, this approach will be useful for
benchmarking of time-resolved EPID dose applications intended for rotational IMRT
QA and adaptive radiation therapy.
PMID- 28516644
TI - Poster - Thur Eve - 69: Electron beam dosimetry in heterogeneous phantoms using
the MAGIC normoxic polymer gel.
AB - Recently, radiation sensitive polymer gels are being used as a reliable dosimetry
method for three-dimensional (3D) verification of radiation doses in clinical
use. Some properties of gel dosimeters have made them useful in verifying complex
situations in electron therapy. The aim of this study was to experimentally
evaluate the influence of tissue inhomogeneities on electron beam dose
distributions by use of polymer gel dosimetry. Another purpose was to evaluate
the appropriateness of polymer gels for electron beam dosimetry applications. A
cylindrical phantom filled with MAGIC polymer gel with a polyacrilic wall (rho =
1.18 g.cm-3 ) was placed in a Perspex water-filled tank exactly underneath the
bone inhomogeneity region .Then, the slab phantom was irradiated with a dose of
5Gy of 8MeV electrons to measure the dose distribution beyond the heterogeneity
region. Afterwards, another cylindrical gel phantom similar to the above was used
and irradiated with the same dose of 15 MeV electrons to measure the dose
distribution beyond the same heterogeneity region. The same mentioned setup was
repeated for measurement of the dose distribution beneath the air heterogeneity
and homogenous phantom. The results of gel dosimetry under bone inhomogeneity
have shown a reduction in dose. This is related to the high mass stopping and
mass scattering powers of bone tissue. In addition, dose enhancement is seen
laterally near the bone-tissue interface, due to increased side scattering of
electrons. Hot and cold scatter lobes under heterogeneity regions are other
effects that can be seen. The results of gel dosimetry under the air
inhomogeneity have shown an increase in dose. This is related to the low mass
stopping and mass scattering powers of the air cavity. When a high energy beam
passes through a low-density medium or an air cavity, electronic equilibrium is
lost along the central axis of the beam .The dose rebuild up is a consequence of
this electronic disequilibrium. An overall good agreement was found between
measurements with gel and with a diode detector for the single beam experiment.
Electron dose distributions are significantly altered in the presence of tissue
inhomogeneities such as bone and air cavities which are related to mass stopping
and mass scattering powers of heterogeneous materials.
PMID- 28516645
TI - Sci-Fri AM: Imaging - 03: Temperature dependence of a SiPM detector for an MR
compatible PET system.
AB - Silicon photomultiplier (SiPM) detectors are rapidly becoming the detector of
choice for research and development of new detectors for positron emission
tomography (PET) due to their combination of high gain, fast timing, compact form
factor and ability to function in a magnetic field. We are investigating using
SiPM based detectors in a compact PET system designed to be inserted into a 7T
animal MRI system and enable simultaneous PET/MRI imaging. In order to understand
the level of thermal stability required for this PET system, we examined the
stability of a prototype SiPM detector vs. temperature. A detector was
constructed using a SensL SPMArray4 SiPM array coupled to a LYSO scintillator
crystal array. The temperature of the detector was varied between 23 and 60
degrees C in 5 degrees C steps. At each temperature setting data were collected
to characterize the detector flood histogram, photopeak amplitude and energy
resolution at 511 keV, timing resolution and signal arrival time. While the flood
image showed no noticeable changes with temperature, the 511 keV photopeak
amplitude showed a linear decrease of 1.5%/ degrees C and the energy resolution
degraded by 0.08%/ degrees C. The timing resolution degraded by 1.5 ns, from 3.5
ns to 5 ns when the temperature changed from 23 to 60 degrees C. Over this
temperature range there was a shift in the signal arrival time of approximately 3
ns. These results demonstrate that the detector can be operated over a wide range
of temperature, giving a large degree of flexibility in choosing an operating
temperature set-point for our PET system.
PMID- 28516646
TI - Sci-Sat AM: Brachy - 03: Feasibility study of the determination of absorbed dose
to water using a fricke based system.
AB - By measuring the dose to water directly a metrology standard, independent of air
kerma, can be developed to make the basis of HDR brachytherapy dosimetry
consistent with current dosimetry methods for external radiation beams. The
Fricke dosimeter system, a liquid chemical dosimeter, provides a means of
measuring the absorbed dose rate to water directly by measuring the radiation
induced change in absorption of the Fricke solution. In an attempt to measure the
absorbed dose to water directly for a 192 Ir HDR brachytherapy source a ring
shaped Fricke holder was constructed from PMMA, essentially following the work of
Austerlitz et al. (Med. Phys. 2008). Benchmark measurements conducted in a 60 Co
beam yielded a standard uncertainty in the absorption reading of 0.16 %,
comparable with previous results in the literature. Measurements of the standard
uncertainty of the control (unirradiated) solution using the holder yielded 0.2
%, indicating good process control and minimal contamination from the holder
itself. However, it was found that the holder sealing method (to allow
measurements in a water phantom) significantly contaminated the Fricke solution,
resulting in an excessive background reading. Irradiations were therefore
conducted in air to determine the feasibility of the procedure. Irradiations with
a 17 GBq source gave a standard uncertainty of approximately 0.5 %, indicating
that the target uncertainty of 1.5% for the measurement of absorbed dose to water
using a Fricke-based primary standard is achievable. This would be comparable
with calorimeter-based systems currently being developed.
PMID- 28516647
TI - Sci-Fri PM: Delivery - 08: Characterizing the spatially varying fluence and
spectra of a kV imaging source for dose calculations.
AB - Kilovoltage (kV) daily image-guided radiotherapy (IGRT) procedures accumulate
radiation dose within the patient that is currently not routinely incorporated in
the treatment plan. As part of the process of developing a patient-specific kV
dose computation tool, the kV x-ray source must be characterized. We propose a
simple, clinically feasible experimental characterization method using in-air
dose measurements along the transverse axis. We determine half-value layer (HVL)
along the transverse axis, from which we derive the HVL-specific mass-absorption
coefficient, which is used to determine beam fluence. These values are
interpolated over the entire field. The spectrum at each interpolation point in
the field is found from HVL and accelerating potential (kVp) using third-party
software Spektr. We use this method to characterize the spatially varying fluence
and spectra of a Varian(r) On-Board Imaging(r) source for energies 80, 100 and
125 kVp. This characterization is used to compute dose within a heterogeneous
phantom, using our previously validated in-house dose computation software, which
we compare with relative dose measurements. We show that for a 10*10 cm2 field
size using no added filtration, the agreement for all three energies is within 2%
for the central depth-dose profile and within 2.6% for the transverse profiles.
This clinically feasible experimental characterization method for kV imaging
sources represents a crucial step in the development of a patient-specific dose
computation tool.
PMID- 28516648
TI - Sci-Sat AM: Brachy - 07: Plastic scintillation detector validation for kV
dosimetry.
AB - PURPOSE: To characterize the plastic scintillation detectors (PSDs) response in
the diagnostic energy range. A fast and adaptable method for real-time dosimetry
in superficial x-ray therapy and interventional radiology is proposed. METHOD: A
PSD (1 mm diameter and 10 mm long) is coupled to a 5 m long optical fiber.
Scintillation photons are guided to a polychromatic photodiode which provides an
electrical current proportional to the input light signal. If the incident energy
spectrum is known, the dose measured in the PSD's polystyrene sensitive volume
can be converted to score dose in any other media such as air, water or soft
tissues using the large cavity theory (LCT). A software simulating x-ray tube
spectra and filtration has been benchmarked and is used for analysis. The method
is confirmed by Monte Carlo simulations. RESULTS: PSDs cannot be assumed energy
independent with low-energy photons as a factor 2 has been observed in the energy
response between 80 kVp and 150 kVp. When the dose is converted to the desired
medium, the PSD's energy dependence is compensated and a 2.1% standard deviation
was observed upon the studied energy ranges, which is inside the measurement and
calculation uncertainties. Percent depth dose (PDD) measurements are in good
agreement with Monte Carlo simulations and results can be improved if the
proposed method is applied to compensate beam hardening. CONCLUSION: PSDs present
great potential for real-time dose measurements with radiologic photon energy.
PMID- 28516649
TI - Poster - Thur Eve - 71: Improved dose accuracy for plan checking IMRT breast
plans.
AB - Dose verification as part of plan checking is a critical component of high
quality patient care. IMSure QA is a software platform used at the BC Cancer
Agency that facilitates dose verification for both conformal and IMRT plans. We
have recently initiated treating breast tangents using IMRT at the Fraser Valley
Centre and noted increased dose discrepancies (mean difference of -3%) between
Eclipse and IMSure's QA module. We identified two potential sources of error: air
flash and tissue heterogeneity. We extend our generated fluences 3cm past the
breast contour and into air to account for breathing, set-up uncertainties and
swelling. IMSure does not account for the fluence in air or air flash. We present
an air-flash-correction factor based on the ratios of TMRs and Phantom Scatter
Factors which use the field sizes of fields with and without the air flash. In
addition, we present a method to improve the heterogeneity correction used by
IMSure to better match that used by AAA. Effectively we remove the IMSure's
inherent heterogeneity correction and manually apply a AAA-based heterogeneity
correction factor. We evaluated our correction factors on a sample of 8 patients
(32 fields) using ANOVA methods to determine which dose corrections most
accurately reproduce Eclipse's values. We found the air-flash correction coupled
with IMSure's inherent-heterogeneity correction has the best dose accuracy (mean
difference improved from -3% to 0.3%). The AAA-heterogeneity correction alone
also improved the accuracy (mean difference improved from -3% to - 1.5%), which
is acceptable for plan checking purposes.
PMID- 28516650
TI - Sci-Fri AM: Imaging - 05: Cone-beam computed tomography for breast biopsy
analysis: Simulations.
AB - PURPOSE: To determine the feasibility and potential utility of cone beam CT on
breast biopsies. METHODS: CBCT simulations were done with a setup which emulates
an MX-20 digital specimen radiography system (Faxitron X-Ray Corporation,
Chicago, IL), albeit a DQE = 1 was assumed. The phantom consisted of a 5mm
diameter cylinder with a length of 5mm, made up of a homogeneous 50:50 mixture of
fibrous and fatty tissue. Small cancerous spheres (lesions) with diameters
ranging from 5 to 500 MUm were embedded. Projections were acquired at
magnification 5 using 26 kV-0.3 mA-3.8 sec beams. Images were reconstructed using
a varied number of projections (50, 100, 150, 300). Values of contrast and SNR
were calculated between the lesions and nearby regions. Noise was estimated by
generating 10 images for each task. Scatter was found to be negligible. RESULTS:
The 50 MUm spheres were only visible when at least 150 projections were used, but
the 100 MUm ones were visible regardless of the number. SNR increased with the
number of projections, whereas contrast was insensitive. For >=100 MUm spheres
contrast ranged from 0.26 on the outer radial edge to 0.28 nearer the center. The
SNRs for 100 MUm spheres were above 5 for reconstructions composed of >=100
projections. Cancerous lesions within a fibrous biopsy may be detectable.
CONCLUSIONS: The findings from this simulation study suggest that CBCT for breast
biopsy characterization via the MX-20 system could be of potential use to see
structures on the order of 100 MUm.
PMID- 28516651
TI - Sci-Fri PM: Delivery - 12: Scatter-B-Gon: Implementing a fast Monte Carlo cone
beam computed tomography scatter correction on real data.
AB - A fast and accurate MC-based scatter correction algorithm was implemented on real
cone-beam computed tomography (CBCT) data. An ACR CT accreditation phantom was
imaged on a Varian OBI CBCT scanner using the standard-dose head protocol (100
kVp, 151 mAs, partial-angle). A fast Monte Carlo simulation developed in the
EGSnrc framework was used to transport photons through the uncorrected CBCT scan.
From the simulation output, the contribution from both primary and scattered
photons for each projection image was estimated. Using these estimates, a
subtractive scatter correction was performed on the CBCT projection data.
Implementation of the scatter correction algorithm on real CBCT data was shown to
help mitigate scatter-induced artifacts, such as cupping and streaking. The
scatter corrected images were also shown to have improved accuracy in
reconstructed attenuation coefficient values. In three regions of interest
centered on material inserts in the ACR phantom, the reconstructed CT numbers
agreed with clinical CT scan data to within 35 Hounsfield units after scatter
correction. These results suggest that the proposed scatter correction algorithm
is successful in improving image quality in real CBCT images. The accuracy of the
attenuation coefficients extracted from the corrected CBCT scan renders the data
suitable for adaptive on the fly dose calculations on individual fractions, as
well as vastly improved image registration.
PMID- 28516652
TI - Sci-Sat AM: Brachy - 11: Improving treatment planning for I-125 lung
brachytherapy using Monte Carlo methods.
AB - 125 I brachytherapy used in conjunction with sublobar resection to treat stage I
non-small cell lung cancer has been reported to improve disease-free and overall
survival rates compared with resection alone. Treatments are planned intra
operatively using seed spacing nomograms or tables to achieve a prescription dose
defined 5 mm above the implant plane. Dose distributions for patients treated
with this technique at the Mayo Clinic Rochester were reanalyzed using a Monte
Carlo (MC) calculation; significant differences were observed between the
standard TG-43 dose calculations and the actual dose delivered as determined by
MC. This work investigates differences between TG-43 calculated prescription
doses and those calculated in more accurate models. Monte Carlo calculations are
performed using the EGSnrc user-code BrachyDose with a number of lung tissue
phantom models including patient CT-derived phantoms. Seed spacing nomograms
using these models are recalculated by determining the dose to the prescription
point using the activities per seed required to produce a prescription dose of
100 Gy with the TG-43 point source formalism. Models using nominal density lung
or CT-derived density lung tissue result in a significant increase in dose to the
prescription point (up to approximately 25%) compared to TG-43 calculated doses.
The differences observed suggest that patients routinely receive significantly
higher doses than planned using TG-43 derived nomograms. Additionally, deviation
from TG-43 increases as seed spacing increases. Media heterogeneities
significantly affect dose distributions and prescription doses for 125 I lung
brachytherapy, underlining the importance of using model-based dose calculation
algorithms to plan and analyze these treatments.
PMID- 28516653
TI - Poster - Thur Eve - 75: Towards MR only simulation: MR based digitally
reconstructed radiograph of head and neck.
AB - PURPOSE: To develop a practical method to obtain bony structures from Magnetic
Resonance (MR) images and to create MR- based digitally reconstructed radiographs
(DRR) for MR only simulation. METHODS AND MATERIALS: Using T1-weighted MR images,
air regions including the sinuses and the airway in the head and neck were
manually contoured. The bone and soft tissue masks were automatically generated
based on the statistical data calculated from the air contour and MR intensities.
"CT like" MR images were generated by mapping the MR intensities of the voxels
within these masks into the CT number ranges of these tissues. The MR-based DRRs
created from "CT like" MR images were quantitatively evaluated using the co
registered MR and CT images of 10 stereotactic radiosurgery CNS patients. Ten
anatomical control points, set on the contours of the skull segmented using a
threshold of 300 HU were used to determine the differences in distance between MR
based DRRs and CT-based DRRs, and to evaluate the geometrical accuracy of MR
based DRRs. RESULTS: The bony structures were visible in the MR-based DRRs. The
mean geometric difference and standard deviation between the ten anatomical
control points on MR- based and CT-based DRRs were -0.03+/-1.11 mm (including
uncertainty of image fusion). The maximum distance difference was 1.67mm.
CONCLUSIONS: The study provides a practical method to generate MR- based DRRs
from MR-only simulations of the head and neck regions. The image quality and
anatomical accuracy of MR-based DRRs is comparable to that of CT-based DRRs.
PMID- 28516655
TI - Poster - Thur Eve - 68: Evaluation and analytical comparison of different 2D and
3D treatment planning systems using dosimetry in anthropomorphic phantom.
AB - PURPOSE: The aim of this study was to evaluate and analytically compare different
calculation algorithms applied in our country radiotherapy centers base on the
methodology developed by IAEA for treatment planning systems (TPS) commissioning
(IAEA TEC-DOC 1583). MATERIAL & METHODS: Thorax anthropomorphic phantom (002LFC
CIRS inc.), was used to measure 7 tests that simulate the whole chain of external
beam TPS. The dose were measured with ion chambers and the deviation between
measured and TPS calculated dose was reported. This methodology, which employs
the same phantom and the same setup test cases, was tested in 4 different
hospitals which were using 5 different algorithms/ inhomogeneity correction
methods implemented in different TPS. The algorithms in this study were divided
into two groups including correction based and model based algorithms. RESULTS: A
total of 84 clinical test case datasets for different energies and calculation
algorithms were produced, which amounts of differences in inhomogeneity points
with low density (lung) and high density (bone) was decreased meaningfully with
advanced algorithms. The number of deviations outside agreement criteria was
increased with the beam energy and decreased with advancement of the TPS
calculation algorithm. CONCLUSION: Large deviations were seen in some correction
based algorithms, so sophisticated algorithms, would be preferred in clinical
practices, especially for calculation in inhomogeneous media. Use of model based
algorithms with lateral transport calculation, is recommended. Some systematic
errors which were revealed during this study, is showing necessity of performing
periodic audits on TPS in radiotherapy centers.
PMID- 28516654
TI - Sci-Fri AM: Imaging - 09: Serial estimation of cross-talk for correction in dual
isotope imaging with dynamic tracers.
AB - The recent radioisotope shortage has led to interest in non-Tc99m-based tracers.
We have developed a novel I-123-labelled myocardial perfusion imaging tracer. We
compare the I123-tracer to the clinical standard of Tc99m tetrofosmin in vivo in
a rat model using a small-animal SPECT/CT camera. SPECT distinguishes different
isotopes based on the different energies of the emitted gamma rays and thus
allows simultaneous comparison of two tracer distributions in the same animal.
Dual-isotope imaging is complicated by cross-talk between the energy windows of
the isotopes. Standard energy-window-based correction methods are difficult to
employ because of the proximity in energy of Tc99m (140keV) and I123 (159keV).
Imaging the second tracer's energy window prior to its injection provides an
estimate of the cross-talk. However, this estimate is only accurate if the tracer
distribution is static. We use serial imaging prior to the introduction of the
second tracer to estimate the dynamics of the first tracer and interpolate the
cross-talk images to provide a more accurate correction. We used rat models of
myocardial disease (n=3). I123 tracer was injected and imaged for one hour at
20min intervals. The Tc99m tetrofosmin was then injected and 30min later, a dual
isotope image was obtained. The impact of this approach is assessed by comparing
the differences in the Tc99m-tetrofosmin image using this method with correction
by simple correction for physical decay. The interpolative approach improves the
accuracy of the correction by 2%-5% and thereby enhances the comparison of the
two tracers.
PMID- 28516656
TI - Sci-Fri AM: Imaging - 02: High resolution detectors for PET mammography.
AB - PURPOSE: With high specificity for malignant breast lesions, dedicated-breast
molecular imaging systems such as positron emission mammography (PEM) have
potential to improve the sensitivity of cancer in women with radio-dense breasts
and to reduce the false-positive rate of breast screening when used as a
diagnostic adjunct. For high signal-to-noise ratio and to minimize the patient
dose, scintillation detectors in a PEM system must have high annihilation photon
detection efficiency. This efficiency can be increased by accepting annihilation
photons from wider incident angles and by using depth-of-interaction (DOI)
measurement within a scintillation crystal to minimize parallax blurring. We have
developed a dual-ended readout block (DERB) detector that uses asymmetry of
signals from photodetectors on either end of a scintillation array to measure DOI
and uses Anger Logic with light sharing to identify interacting crystal elements
while minimizing the number of photodetectors required. METHODS: A prototype DERB
detector was constructed from two arrays of silicon photomultipliers (SiPM), two
glass optical diffusers, and an array of LYSO scintillation crystals. Assembled,
each of the 2 * 2 SiPM arrays detect photons that are dispersed via the optical
light diffusers originating from either end of 3 * 3 scintillation crystal
elements. We evaluated the ability of the detector to identify the crystal index,
resolve DOI, and discriminate energy. RESULTS: The DERB detector was able to
clearly identify interacting crystal elements, to measure DOI with 5mm resolution
in 2mm * 2mm * 20mm crystals, and to achieve an average energy resolution of 20%.
CONCLUSIONS: The DERB detector characteristics suggest that it can be used to
reduce the parallax effect in PEM systems without increasing the number of
required photodetectors. Further investigation is warranted to improve
performance with high optical photon detection efficiency photodetectors.
PMID- 28516657
TI - Sci-Fri PM: Delivery - 04: Quantitative air communication testing of ion chambers
for megavoltage dosimetry.
AB - The valid application of the standard correction for air density (PTP in the TG
51 protocol) requires that for a vented ion chamber (basically all reference
class ion chambers) the air cavity does indeed communicate directly with the
external environment. However, this assumption is not tested by users, and not
universally verified by calibration laboratories. A system has therefore been
developed at the National Research Council to test air communication of
cylindrical and parallel-plate ion chambers. The systems is based on measurements
in a vacuum vessel with a Sr-90 check source; the procedure is simple and quick
and can measure ionization currents over the pressure range 0 kPa (atmospheric)
to -20kPa (0.8 atm) with an uncertainty better than 0.2%. Investigation of a wide
range of chamber types shows that for a coarse check on chamber performance
(i.e., that the chamber is vented to atmosphere) measurement at a single polarity
is sufficient (total test time less than 15 minutes) but for accurate
characterization of the chamber performance, data at both polarities must be
acquired. The accuracy of the system means that it can potentially be used to
investigate: i) the validity of the pressure correction, and ii) the source of
the polarity correction in cylindrical and parallel-plate chambers. The air
communication test will be implemented as part of the standard calibration
services provided by NRC for external beam radiotherapy.
PMID- 28516658
TI - Sci-Fri PM: Delivery - 07: Cyberknife relative output factor measurements using
fiber-coupled luminescence, MOSFETS and RADPOS dosimetry system.
AB - Novel dosimetry systems based on Al2 O3 :C radioluminescence (RL) and a 4D
dosimetry system (RADPOS) from Best Medical Canada were used to measure the
relative output factor (ROF) on Cyberknife. Measurements were performed in a
solid water phantom at the depth of 1.5 cm and SSD = 78.5 cm for cones from 5 to
60 mm. ROFs were also measured using a mobileMOSFET system (Best Medical Canada)
and EBT1 and EBT2 GAFCHROMIC(r) (ISP, Ashland) radiochromic films. For cone sizes
12.5-60 mm all detector results were in agreement within the measurement
uncertainty. The microMOSFET/RADPOS measurements (published corrections applied)
yielded ROFs of 0.650 +/- 1.9%, 0.811 +/- 0.9% and 0.843 +/- 1.7% for the 5, 7.5
and 10 mm cones, respectively, and were in excellent agreement with radiochromic
film values (averaged for EBT1 and EBT2) of 0.645 +/- 1.4%, 0.806 +/- 1.1% and
0.859 +/- 1.1%. Monte-Carlo calculated correction factors were applied to the RL
readings to correct for excessive scatter due to the relatively high effective
atomic number of Al2 O3 (Z=10.2) compared to water for the 5, 7.5 and 10 mm
cones. When these corrections are applied to our RL detector measurements, we
obtain ROFs of 0.656 +/- 0.3% and 0.815 +/- 0.3% and 0.865 +/- 0.3% for 5, 7.5
and 10 mm cones. Our study shows that the microMOSFET/RADPOS and optical fiber
coupled RL dosimetry system are well suited for Cyberknife cone output factors
measurements over the entire range of field sizes, provided that appropriate
correction factors are applied for the smallest cone sizes (5, 7.5 and 10 mm).
PMID- 28516659
TI - Sci-Sat AM: Brachy - 06: Monte carlo DNA damage simulations of kV cbct radiation.
AB - When performed daily, cone beam CT (CBCT) images can accumulate radiation dose to
non-negligible levels. Because kV x-rays have a larger relative biological
effectiveness (RBE) than its MV x-rays, the accumulated absorbed dose needs to be
multiplied by an appropriate RBE to better evaluate the impact of CBCT dose in a
treatment planning context. We investigated this question using PENLEOPE
simulations to look in detail at the electron energy spectra produced by kV x
rays and Co-60 gamma-rays in biologically motivated geometries. The electron
spectra were input into the published Monte Carlo Damage Simulation (MCDS) and
used to estimate the average number of double strand breaks (DSBs) per Gy per
cell. Our results suggest an approximately 10% increase in the RBE for DSB
induction. For the majority of treatment planning scenarios where imaging dose is
only a small fraction of the total delivered dose to target volumes and organs at
risk, the increase in RBE is not critical to be factored in, however for it may
play a significant role in predicting the induction of secondary cancers.
PMID- 28516661
TI - Sci-Fri PM: Delivery - 11: Accuracy considerations in modern radiation oncology:
An update.
AB - The most recent reviews of accuracy requirements in radiation oncology were
published in the 1990s, primarily in an era that was transitioning from 2-D to 3
D conformal radiation therapy (CRT). Since then, the technology associated with
radiation oncology has changed dramatically. The combination of various forms of
imaging for radiation therapy planning, treatment planning software, dose
delivery technology including 4-D considerations as well as in-room daily image
guidance has resulted in new perspectives on accuracy considerations. The
underlying hypothesis for the use of these advanced technologies is that loco
regional control of cancer remains a significant barrier to cancer cure for many
common cancers and that better dose distributions will translate into better
outcomes. However, further clinical gain using these new technologies may be
limited by single or compounded uncertainties associated with the entire
treatment process. Thus, it is important to understand what factors should be
considered in determining accuracy requirements as well as the realistic
expectations of uncertainties that exist within the total treatment process. The
need for accuracy is based on clinical requirements such as the steepness of dose
response curves, inherent heterogeneity in patient response to treatment, and the
level of accuracy that is practically achievable. Statements on accuracy are
dependent on the technology used and the reality of what is practically
achievable and necessary. This review highlights some of the major differences
between accuracy requirements as determined in the 2-D RT and 3-D CRT era versus
the modern era of intensity modulated, image-guided, 4-D radiation therapy.
PMID- 28516660
TI - Sci-Fri AM: Imaging - 04: SPECT-based functional lung imaging in the prediction
of radiation pneumonitis: A retrospective clinical and dosimetric correlation.
AB - PURPOSE: To investigate whether functionally-weighted dose-volume histogram (DVH)
parameters are more predictive of radiation-induced pneumonitis (RP) than
standard parameters such as V20 and mean lung dose (MLD). MATERIALS AND METHODS:
A retrospective chart review identified 26 patients who received curative-intent
radiation therapy for primary carcinoma of the lung. Prior to treatment, all
patients received single photon emission computed tomography (SPECT) to assess
both lung ventilation and lung perfusion. Patients were assessed for clinical RP
using standard criteria and were separated into a non-RP group (RP grade < 2) and
an RP-group (RP grade >= 2). Standard DVH parameters (V10, V20, V30, MLD) and
their function-weighted counterparts (for perfusion: pF10, pF20, pF30, pMLD; for
ventilation: vF10, vF20, vF30, vMLD) were evaluated for each group. Receiver
operating characteristics (ROC) curves were created and the area under the curve
(AUC) computed. RESULTS: 7 of 26 patients had grade >= 2 pneumonitis. Both pF20
(p=0.022) and vF20 (p=0.036) were significantly different between the 2 groups;
V20 was not (p=0.06). Both pF30 (p=0.008) and vF30 (p=0.025) were significantly
different between groups while V30 failed to reach significance (p=0.072).
Standard MLD (p=0.011), pMLD (p=0.001), and vMLD (p=0.011) were all significantly
different. The ROC curves indicated that both the perfusion-weighted parameters
and the ventilation-weighted parameters outperformed the standard DVH parameters
as predictors of RP grade >=2. CONCLUSIONS: SPECT-based, function-weighted DVH
parameters appear to be useful as predictors of RP.
PMID- 28516662
TI - Sci-Sat AM: Brachy - 10: Adaptation of the CVT algorithm for catheter
optimization in high dose rate brachytherapy.
AB - INTRODUCTION: In interstitial high dose rate (HDR) brachytherapy, the number and
positions of the catheter are usually fixed by the use of a template, without
considering tumor size and shape. In this work, we present a simple and fast
method to optimize both the number and position of catheters, using a modified
version of the Centroidal Voronoi Tessellations (CVT) algorithm. METHODS: 8
prostate HDR clinical cases were chosen randomly to test our method. The
treatment plan was obtained from a research version of IPSA. Clinically relevant
dosimetric parameters were computed to evaluate our method and help optimizing
the CVT algorithm parameters. Plans were generated with a specified number of
catheters ranging from 9 to 18 and compared to the clinical cases with 17
catheters. RESULTS: The computation time to optimize the positions of a specific
number of catheters was 1.5 s. The prostate V100 was better than the clinical
case up to 12 catheters. Plans with 9 or less catheters would not be clinically
acceptable in terms of prostate V100 and D90. High conformity is achieved whether
the number of catheters used. The V75 of the bladder seems slightly higher, but
not significant clinically. All other dosimetric indices are as good as the
clinical plan. CONCLUSION: We have devised a simple, fast and efficient method to
optimize the number and position of catheters in HDR brachytherapy. Ultimately,
this catheter optimization algorithm could be coupled with a 3D ultrasound system
to allow real-time guidance and planning for any interstitial brachytherapy
sites.
PMID- 28516663
TI - Poster - Thur Eve - 74: A set of tests designed for electron dose calculation
algorithm verification during a treatment planning system upgrade.
AB - A set of tests were designed to verify an electron algorithm effectively and
quickly during a treatment planning system upgrade. Based on TG-53 report's
suggestion and the assumption that the algorithm is well commissioned before the
upgrade, the tests spot-check the output factors, depth doses, off-axis doses and
treatment field sizes. The field sizes of 4*4, 6*6, 10*10, 15*15, 20*20 and 25*25
are to be tested. Four test plans are created for each field size, i.e., for open
field, for extended SSD, for shaped field, and for bolus field. Fixed MU setting
is recommended to avoid a possible plan normalization issue. The parameters to be
recorded and compared include doses at dmax , R50 and Rp along central axis,
which contain output and depth dose information, doses at four off-axis points in
dmax plane, which contain off-axis dose and beam symmetry information, and FWHMs
at dmax . For the plans other than open field only doses at dmax are checked. The
tests were performed successfully during a planning system upgrade. The whole
test can be completed in approximately 12 hours if the workload is distributed
into multiple task carriers. It was found that most of the data agree very well
between the old and the new version of the algorithm while some of the Rp or R50
doses deviated more than other data, which prompted a depth dose check. PDD
comparisons were performed for the involved fields and it was found there were
less than 0.5 mm PDD shifts occurred.
PMID- 28516664
TI - Sci-Fri AM: Imaging - 08: Comparison of single and dual layer detector blocks for
pre-clinical MRI-PET.
AB - Our group is developing a small animal PET scanner which would fit in a 7 Tesla
MRI scanner to provide simultaneous PET and MR acquisitions and images. There is
very little room for the PET detectors and we must use nonmagnetic materials.
This presentation describes preliminary work with two PET detectors consisting of
LYSO blocks each with two crystal layers: 49 1.67*1.67*6.0 mm on the bottom layer
and 36 4.0 mm deep crystals on the top layer. These are mounted on SensL 4*4
arrays of silicon photo-multipliers whose outputs are multiplexed to provide
three signals: Energy, X, Y. These detectors were mounted on translation stages
and scanned past a 0.25 mm diameter 370 MBq Na-18 source embedded in tissue
equivalent plastic. The results were compared with similar single layer crystal
blocks with 10 mm deep crystals to assess the advantage of dual layer crystals to
reduce radial blurring in a PET scanner with a diameter of only 64 mm. The
ability to identify correctly each crystal is reported as its resolvability
index, (RI), defined as the (crystal response FWHM)/(crystal's separation) in the
crystal identification matrix. For the dual layer block RI =0.44, and for dual
layer block RI=0.22. The coincidence response resolution for the single layer
block varied from 1.23+/-0.05 mm at the centre of the scanner to 3.09+/-0.10 mm
at 15.8 mm radius, while the dual layer block varied from 1.31+/-0.06 to 1.96+/
0.51 mm over the same range, confirming the Monte-Carlo simulations showing
reduced radial blurring.
PMID- 28516665
TI - Fifty-Eighth Annual Meeting of the Canadian Organization of Medical Physicists
and the Canadian College of Physicists in Medicine.
PMID- 28516666
TI - Sci-Fri AM: Imaging - 01: Feasibility of estimating choline kinase activity with
kinetic modeling of 18F-fluorocholine pet imaging of prostate cancer.
AB - Prostate cancer (PCa) detection and delineation remains a challenge for medical
imaging. Studies have shown 18 F-Fluorocholine (FCH) PET imaging to be a
promising modality in the detection of recurrent PCa. Detection of denovo PCa is
more challenging, as lesions such as benign prostatic hyperplasia (BPH) may
adversely affect the sensitivity and specificity of the modality. PCa and BPH
have been shown to exhibit similar uptake of FCH, yet it has been shown that
phosphocholine levels are much more elevated in PCa compared to BPH. Therefore,
it would be useful to measure the activity of phosphorylation via choline kinase
(k3 ) in order to differentiate PCa from BPH. This work examines the feasibility
of using a compartmental model to estimate k3 with dynamic 18 F-Fluorocholine PET
imaging. JSim software [1] was used to simulate the compartmental model for FCH
exchange. A simulated tissue curve was generated using predefined parameters and
the model's ability to estimate these parameters through fitting of the simulated
tissue curve with and without noise was investigated. The fitting procedure was
performed using the non-negative least squares algorithm in MATLAB after the
equation governing fitting was linearized. In the noiseless case, the model was
able to accurately identify the values of each rate parameter. For the noisy case
with an SNR of 10:1, the mean estimated k3 for 10,000 runs had a coefficient of
variation of 14.9%. The kinetic model shows promise for quantifying k3 , which
would allow the differentiation of malignant and benign tumours of the prostate.
PMID- 28516667
TI - Sci-Fri PM: Delivery - 03: Spine SBRT: Treating multiple vertebrae using cone
beam CT image-guidance and the hexapod robotic couch.
AB - PURPOSE: The intent of spinal SBRT is to maximize the biological effective dose
and improve local control, while sparing the adjacent spinal cord. We report on
the spinal SBRT positional accuracy for multiple, consecutive vertebrae in a
single course, using the Elekta Synergy-S and BodyFIX immobilization systems.
METHODS: After initial patient adjustment, verification cone-beam CT (CBCT)
images were acquired before, during and after treatment. These images were used
to assess immobilization and correct any misalignment exceeding 1 mm or 1 degrees
, in all six degrees-of-freedom using the HexaPOD robotic couch. This analysis is
based on 415 verification images from 67 consecutive courses of treatment. These
treatment courses comprised 25 single thoracic vertebrae, 16 multiple thoracic
vertebrae, 20 single lumbar vertebrae and 6 multiple lumbar vertebrae. RESULTS:
The absolute intra-fraction motion averaged over all directions (+/-std dev.) for
the T-single, T-multiple, L-Single and L-Multiple was 0.54 (+/-0.73) mm, 0.54 (+/
0.88) mm, 0.36 (+/-0.57) mm, and 0.47 (+/-0.63) mm respectively. The percentage
that exceeded the 1.5 mm planning margin was 3.8%, 4.0%, 1.0% and 0.85%
respectively. T-spine treatments were out-of-tolerance more frequently than the L
spine. There was a statistically significant difference between single and
multiple lumbar treatments (unpaired t-test, p<0.01), but this was not clinically
significant as 99% were within our 1.5 mm margin. CONCLUSIONS: Near-rigid
immobilization with the acquisition of intra-fraction CBCT images and the
correction of misalignments in all six degrees-of-freedom provides the necessary
precision to safely perform SBRT of consecutive spinal metastases within one
course of treatment.
PMID- 28516668
TI - Sci-Fri PM: Delivery - 06: A generalized solution to the wide field array
calibration method.
AB - Multi detector arrays are commonly used in radiation oncology for IMRT and Linac
QA. The calibration of detector arrays is usually based on the wide field
calibration technique. Unfortunately small beam changes between measurements will
result in large error propagation. The present work introduces a generalized
modified version of the wide field calibration method, robust against measurement
to measurement variation. Our generalized framework uses an unlimited number of
measurement pairs, n geometric positions providing n(n-1)/2 pairs. We solve this
large over determined linear system using least squares with gradient method.
Measurements were made on an Elekta synergy 6 MV beam with two IBA Matrixx
detectors, each containing a 32 * 32 array (1024) of vented pixel ionization
chambers. Data acquisition was by the IBA Omnipro Advance software, version 1.2
running in the "ONLINE" cine mode with a 10 sec integration time. Continuous beam
sampling (10 seconds long) measured over 10 minutes demonstrated why consistent
calibration using the conventional wide field calibration is a challenge. Overall
signal changes of 1.6%, flatness changes of 0.3% and the beam symmetry changes of
0.2% over the full 10 minute beam-on time were observed. For the purpose of
testing and demonstration of our method, we have chosen to make measurements in 5
geometric orientations relative to the beam, including 1 reference position, 2
rotations and 2 translations. With our method we were able to calibrate all 1024
detectors to better than 0.6% total uncertainty as demonstrated against inter and
intra MatriXX comparison.
PMID- 28516669
TI - State of the Art: Novel Applications for Deep Brain Stimulation.
AB - OBJECTIVES: Deep brain stimulation (DBS) is a rapidly developing field of
neurosurgery with potential therapeutic applications that are relevant to
conditions traditionally viewed as beyond the limits of neurosurgery. Our
objective, in this review, is to highlight some of the emerging applications of
DBS within three distinct but overlapping spheres, namely trauma,
neuropsychiatry, and autonomic physiology. REVIEW METHODS: An extensive
literature review was carried out in MEDLINE, to identify relevant studies and
review articles describing applications of DBS in the areas of trauma,
neuropsychiatry and autonomic neuroscience. RESULTS: A wide range of applications
of DBS in these spheres was identified, some having only been tested in one or
two cases, others much better studied. CONCLUSIONS: We have identified various
avenues for DBS to be applied for patient benefit in cases relevant to trauma,
neuropsychiatry and autonomic neuroscience. Further developments in DBS
technology and clinical trial design will enable these novel applications to be
effectively and rigorously assessed and utilized most effectively.
PMID- 28516670
TI - Endoscopic versus open radial artery harvesting: A meta-analysis of randomized
controlled and propensity matched studies.
AB - BACKGROUND: We sought to investigate the impact of radial artery harvesting
techniques on clinical outcomes using a meta-analytic approach limited to
randomized controlled trials and propensity-matched studies for clinical
outcomes, in which graft patency was analyzed. METHODS: A systematic literature
review was conducted using PubMed and MEDLINE to identify publications containing
comparisons between endoscopic radial artery harvesting (ERAH) and open
harvesting (ORAH). Only randomized controlled trials and propensity-matched
series were included. Data were extracted and analyzed with RevMan. The primary
endpoint was wound complication rate, while secondary endpoints were patency
rate, early mortality, and long-term cardiac mortality. RESULTS: Six studies
comprising 743 patients were included in the meta-analysis. Of them 324 (43.6%)
underwent ERAH and 419 (56.4%) ORAH. ERAH was associated with a lower incidence
of wound complications (odds ratio: 0.33, confidence interval 0.14-0.77; p =
0.01). There were no differences in graft patency, and early and long-term
cardiac mortality between the two techniques. CONCLUSION: ERAH reduces wound
complications and does not affect graft patency, or short- and long-term
mortality compared to ORAH.
PMID- 28516671
TI - The aggressive peripheral T-cell lymphomas: 2017.
AB - BACKGROUND: T-cell lymphomas make up approximately 10%-15% of lymphoid
malignancies. The frequency of these lymphomas varies geographically, with the
highest incidence in parts of Asia. DIAGNOSIS: The diagnosis of aggressive
peripheral T-cell lymphoma (PTCL) is usually made using the World Health
Organization classification. The ability of hematopathologists to reproducibly
diagnose aggressive PTCL is lower than that for aggressive B-cell lymphomas, with
a range of 72%-97% for the aggressive PTCLs. Risk Stratification: Patients with
aggressive PTCL are staged using the Ann Arbor Classification. Although somewhat
controversial, positron emission tomography scans seem to be useful as they are
in aggressive B-cell lymphomas. The specific subtype of aggressive PTCL is an
important risk factor with the best survival seen in anaplastic large-cell
lymphoma-particularly young patients with the anaplastic lymphoma kinase positive
subtype. RISK-ADAPTED THERAPY: Anaplastic large-cell lymphoma is the only
subgroup to have a good response to a CHOP-like regimen. Angioimmunoblastic T
cell lymphoma has a prolonged disease-free survival in only ~20% of patients, but
younger patients who have an autotransplant in remission seem to do better. PTCL
not otherwise specified is not one disease. Anthracycline-containing regimens
have disappointing results, and a new approach is needed. Natural killer/T-cell
lymphoma localized to the nose and nasal sinuses seems to be best treated with
radiotherapy-containing regimens and the majority of patients are cured.
Enteropathy-associated PTCL and hepatosplenic PTCL are rare disorders with a
generally poor response to therapy although selected patients with enteropathy-
associated PTCL seem to benefit from intensive therapy.
PMID- 28516672
TI - Two-photon imaging of fiber-coupled neurons.
AB - Optical coupling between a single, individually addressable neuron and a properly
designed optical fiber is demonstrated. Two-photon imaging is shown to enable a
quantitative in situ analysis of such fiber-single-neuron coupling in the live
brain of transgenic mice. Fiber-optic interrogation of single pyramidal neurons
in mouse brain cortex is performed with the positioning of the fiber probe
relative to the neuron accurately mapped by means of two-photon imaging. These
results pave the way for fiber-optic interfaces to single neurons for a
stimulation and interrogation of individually addressable brain cells in chronic
in vivo studies on freely behaving transgenic animal models, as well as the
integration of fiber-optic single-neuron stimulation into the optical imaging
framework.
PMID- 28516673
TI - Choice among two and three alternatives.
AB - Although choice between two alternatives has been widely researched, fewer
studies have examined choice across multiple (more than two) alternatives. Past
models of choice behavior predict that the number of alternatives should not
affect relative response allocation, but more recent research has found
violations of this principle. Five pigeons were presented with three concurrently
scheduled alternatives. Relative reinforcement rates across these alternatives
were assigned 9:3:1. In some conditions three keys were available; in others,
only two keys were available. The number of available alternatives did not affect
relative response rates for pairs of alternatives; there were no significant
differences in behavior between the two and three key conditions. For two birds
in the three-alternative conditions and three birds in the two-alternative
conditions, preference was more extreme for the pair of alternatives with the
lower overall pairwise reinforcer rate (3:1) than the pair with higher overall
reinforcer rate (9:3). However, when responding during the changeover was removed
three birds showed the opposite pattern in the three-alternative conditions;
preference was more extreme for the pair of alternatives with the higher overall
reinforcer rate. These findings differ from past research and do not support
established theories of choice behavior.
PMID- 28516674
TI - Selection by consequences, behavioral evolution, and the price equation.
AB - Price's equation describes evolution across time in simple mathematical terms.
Although it is not a theory, but a derived identity, it is useful as an
analytical tool. It affords lucid descriptions of genetic evolution, cultural
evolution, and behavioral evolution (often called "selection by consequences") at
different levels (e.g., individual vs. group) and at different time scales (local
and extended). The importance of the Price equation for behavior analysis lies in
its ability to precisely restate selection by consequences, thereby restating, or
even replacing, the law of effect. Beyond this, the equation may be useful
whenever one regards ontogenetic behavioral change as evolutionary change,
because it describes evolutionary change in abstract, general terms. As an
analytical tool, the behavioral Price equation is an excellent aid in
understanding how behavior changes within organisms' lifetimes. For example, it
illuminates evolution of response rate, analyses of choice in concurrent
schedules, negative contingencies, and dilemmas of self-control.
PMID- 28516676
TI - Retention of pigment stem cells in Rhododenol-induced leukoderma: Pathological
investigation of 11 patients.
PMID- 28516677
TI - Poster - Thur Eve - 42: Dynamic delivery quality assurance on Elekta linacs.
AB - Introduction Recently, Elekta linacs have gained the capability to deliver
dynamic fields, such as sliding window IMRT or VMAT fields. Because of the
potential complexity of such delivery modes, linac QA and patient-specific QA are
of prime importance. The aim of this paper is to explain the fundamental concepts
of this new mode of operation on Elekta linacs as well as to introduce the linear
alpha slit, a novel dynamic QA sequence which allows the performance of the
delivery system to be objectively aassessed against dosimetric measurements. In
the Elekta dynamic mode, dose rate can only take a limited number of
discontinuous values. We have used the uniform slit, a simple slit moving at a
constant speed across the field to verify how the linac selects leaf speed and
dose rate for a given MU setting. Based on this, we expose the principles behind
the linear-alpha slit, which exhibits two main characteristics: 1) it exercises
the linac over a range of dose rates and 2) it produces a dose distribution which
is theoretically equivalent to the uniform slit. Discrepancies between
measurements of the linear-alpha slit and the uniform slit directly reflects
problems with the delivery. The linear-alpha slit has been recently introduced in
our routine monthly linac QA. We hope it will nicely complement patient-specific
QA, and exising linac-QA.
PMID- 28516675
TI - Analysis of platelet-reactive alloantibodies and evaluation of cross-match
compatible platelets for the management of patients with transfusion
refractoriness.
AB - BACKGROUND: Cross-match-compatible platelets can improve corrected count
increments (CCIs) in alloimmunised patients with transfusion refractoriness.
However, only a few studies mentioned that the specificities of platelet-reactive
alloantibodies can predict high reactivity in cross-match assays among these
patients. METHODS: A total of 204 medical records of patients who were refractory
to random single-donor apheresis platelets between January 2014 and December 2014
were enrolled. Platelet-reactive antibodies in patients' serum were screened by
an enzyme-linked immunosorbent assay (ELISA).The platelet cross-match assays were
performed by a solid-phase adherence assay. The specificities of human leukocyte
antigen (HLA) class I and human platelet antigens (HPAs) alloantibodies were
determined by Luminex Single Antigen and Monoclonal Antibody-specific
Immobilization of Platelet Antigens (MAIPA) assays, respectively. RESULTS: Anti
HLA and anti-HPA alloantibodies were found in 114 of 204 (55.88%) patients,
including 110 (96.49%) with anti-HLA alloantibodies only, 2 (1.75%) with anti-HPA
alloantibodies (anti-GPIIb/IIIa) only and 2 (1.75%) with both anti-HLA and anti
HPA alloantibodies (anti-HPA-3a and anti-HPA-5b). The most common HLA class I
alloantibody phenotypes in cross-match-incompatible patients were HLA-A23
(59.38%), -A24 (50.00%), -A02 (43.75%), -B27 (65.63%), -B40 (50.00%), -B18
(46.88%) and -B07 (43.75%). A total of 480 cross-matched platelet units were
administered in 82 of 114 alloimmunised patients with a mean CCI of 7800 +/-
5200, a significant improvement over random platelet units (P < 0.001).
CONCLUSIONS: No development of additional platelet alloantibodies was observed
during this platelet transfusion regiment. This study showed that transfusion of
cross-match-compatible platelet units offers effective and safe management of
platelet transfusion refractoriness (PTR). The finding of alloantibodies among
cross-match-incompatible cases can be used as predictors for platelet donor
selection.
PMID- 28516678
TI - Poster - Thur Eve - 53: Analysis of the distribution of dose delivery during
respiratory-gated step-and-shoot IMRT for lung cancer radiotherapy.
AB - Respiratory motion is a large source of dosimetric error when treating lung
cancer with Intensity Modulated Radiation Therapy (IMRT). The asynchronicity of
the tumour motion and the multileaf collimator (MLC) used to modulate the
radiation beam intensity, leads to the interplay effect. One method to account
for this effect is respiratory gating. Treatment planning optimization for gated
IMRT is performed on a subset average 4D-CT which includes the phases surrounding
end exhalation. However, this assumes that the beam delivery will be evenly
distributed amongst those phases. This study investigates the distribution of
beam delivery during gated step-and-shoot IMRT (SS-IMRT) for both early and late
stage non-small cell lung cancer (NSCLC). Four Stage I NSCLC patients, prescribed
a dose of 54 Gy in 3 fractions, and five Stage III NSCLC patients, prescribed a
dose of 60 Gy in 30 fractions, were retrospectively planned with high and low
modulation beams-IMRT, and delivered using the QUASARTM Programmable Respiratory
Motion Platform with 15 mm and 20 mm peak-to-peak sinusoidal motion and real
patient breathing motion. The percent monitor units delivered at each phase were
compared. For Stage I patients, the monitor units delivered were evenly
distributed over the gating window due to a high number of monitor units
delivered per control point. For Stage III patients, as the complexity of SS-IMRT
increases, there were more monitor units delivered in the initial gating phase.
This dose discrepancy could potentially lead to geographic miss of the tumour and
should be taken into account during treatment planning.
PMID- 28516679
TI - Poster - Thur Eve - 24: Clinical application of the new dosimetry formalism for
composite nonstandard beams.
AB - The IAEA-AAPM new dosimetry formalism [Med. Phys. 35, 5179 (2008)] was applied to
clinical IMRT quality assurance (QA). Twenty different IMRT QA fields were
created on the CT images of a 30*30*17 cm3 Solid WaterTM phantom. Two Farmer-type
chambers, Exradin A12 and NE2571, and a smaller Exradin A1SL ionization chamber
were cross-calibrated against a reference detector, the PTW micro liquid ion
chamber (microLion), in the lowest dose gradient region in each IMRT QA field
delivery. Based on the new dosimetry formalism, the clinical correction factor
was measured in a fully-rotated delivery and a delivery at a single gantry angle,
a collapsed delivery. For the calibrated Exradin A12, the measured dose with the
clinical correction factor was compared with a calculated dose using Monte Carlo
(MC) methods. The clinical correction factor deviated from unity by up to 2.4%
and 3.7% in the fully-rotated and collapsed deliveries, respectively, depending
on the dose distribution in the chamber collecting volume. For the Exradin A1SL,
the correction factor was generally closer to unity due to the reduced dose
gradient on the smaller collecting volume. In the fully-rotated delivery, the
measured dose with the clinical correction factor is different from the MC
calculated dose to within 4%; while the discrepancy was greater, up to 8%, in the
collapsed delivery due to the much heterogeneous dose distribution in the chamber
collecting volume. This work proves that the suggested dosimetry technique is
effective to improve the dosimetric consistency of clinical IMRT QA.
PMID- 28516681
TI - Poster - Thur Eve - 35: Characterization of performance of two deformable
registration software.
AB - PURPOSE: To evaluate the performance of two deformable registration softwares (a
commercial and an open source software) using cone-beam computed tomography
(CBCT) images. METHODS: We used a set of 34 lung patients with generally large
tumors each having between 1 and 20 CBCT scans. A radiation oncologist resident
contoured GTVs on each CBCTs using planning CT contours as reference. Deformable
registrations were performed on CT scans to adapt it to the first CBCT of each
patient independently with both software. Then each CBCT was registered to the
next CBCT. Contour structures have been deformed in the process for the
commercial software and for the open source software contours have been drawn
manually on deformed images. RESULTS: Mean remaining volume (+/-SD) for manual
GTV contours was 59 +/- 32 %. GTVs obtained with the open source software were
closer to the manual GTV in size than the commercial software. Mean relative
errors on volume were 45 +/- 60 % for the commercial system (33 patients) and 9
+/- 2 % for the open source software (6 patients). Relative errors for the
commercial software increased exponentially with the volume reduction but were
constant over all CBCT for the open source software. Mean Jaccard and Dice's
index were 0.57 and 0.71 for the commercial software (24 patients) and 0.80 and
0.88 for the open source software (6 patients). CONCLUSION: Open source software
shown tendency to give better results than commercial software but was slower
than the commercial software.
PMID- 28516680
TI - Poster - Thur Eve - 64: Evaluation of SmartArc and RapidArc for lung SBRT
treatment planning and delivery.
AB - OBJECTIVES: To evaluate the performance of RapidArc(r) (Eclipse 10.0.28) and
SmartArc(r) (Pinnacle 9.0) radiotherapy plans for lung stereotactic body
radiation therapy (SBRT) in terms of dosimetric plan quality, delivery
efficiency, inhomogeneity corrections and accuracy of dose delivery using a
custom-built heterogeneity insert for ArcCHECKTM (Sun Nuclear Corp., FL, USA).
METHODS: SmartArc(r) and RapidArc(r) plans were generated for 10 patients. The
quality of the plans was evaluated in terms of conformity indices (R100 and R50 )
and the dose to the organs at risk. The efficiency was evaluated in terms of the
monitor units (MUs) required for a given prescription dose. For dose
verification, we designed and manufactured a heterogeneity insert for ArcCHECKTM
with densities that simulate soft tissue, lung, bone, and air and having multiple
locations for point dose measurements. Accuracy of dose delivery was assessed
using gamma analysis. RESULTS: The overall plan quality was similar when
comparing SmartArc(r) with RapidArc(r). However, RapidArc(r) plans required
significantly more MUs-up to 72%TMcompared with SmartArc(r) plans (p<0.001).
ArcCHECKTM measurements in the presence of inhomogeneities showed better
agreement for SmartArc(r) plans. CONCLUSION: Plan quality for SmartArc(r) and
RapidArc(r) was comparable. However, SmartArc(r) plans were more efficient,
requiring significantly fewer monitor units, and were delivered more accurately
in a non-homogeneous phantom. With the custom-built heterogeneity insert,
ArcCHECKTM can be used efficiently to verify inhomogeneity corrections and dose
delivery accuracy for lung SBRT plans.
PMID- 28516682
TI - Poster - Thur Eve - 46: The upcoming international code of practice for small
static photon field dosimetry.
AB - The increased use of small photon fields in stereotactic and intensity-modulated
radiotherapy has raised the need for standardizing the dosimetry of such fields
using procedures consistent with those for conventional radiotherapy. An
international working group, established by the IAEA in collaboration with AAPM
and IPEM, is finalising a Code of Practice for the dosimetry of small static
photon fields. Procedures for reference dosimetry in nonstandard machine specific
reference (msr) fields are provided following the formalism of Alfonso et al.
(Med. Phys. 35: 5179; 2008). Reference dosimetry using ionization chambers in
machines that cannot establish a conventional 10 cm * 10 cm reference field is
based on either a direct calibration in the msr field traceable to primary
standards, a calibration in a reference field and a generic correction factor or
the product of a correction factor for a virtual reference field and a correction
factor for the difference between the msr and virtual fields. For the latter
method, procedures are provided for determining the beam quality in non-reference
conditions. For the measurement of field output factors in small fields,
procedures for connecting large field measurements using ionization chambers to
small field measurements using high-resolution detectors such as diodes, diamond,
liquid ion chambers, organic scintillators and radiochromic film are given. The
Code of Practice also presents consensus data on correction factors for use in
conjunction with measured, detector-specific output factors. Further research to
determine missing data according to the proposed framework will be strongly
encouraged by publication of this document.
PMID- 28516684
TI - Poster - Thur Eve - 28: Optimization of a prostate cancer IGRT protocol.
AB - Our image-guided radiation therapy (IGRT) protocol for post-prostatectomy
patients involves acquiring a kV cone beam computed tomography (CBCT) dataset at
each fraction and shifting the treatment couch to align the surgical clips. This
IGRT strategy requires significant resources, and delivers non-negligible dose to
normal tissues. The objective of this work is to evaluate this IGRT protocol
against two alternative strategies in terms of the dose-volume statistics for
target and organ at risk regions. Our method involves deforming the planning CT
to the CBCT dataset acquired at each fraction, computing dose on the deformed
dataset, and inversely transforming the dose back onto the original planning CT
dataset. The treatments of six patients were evaluated assuming three IGRT
scenarios: no IGRT, daily IGRT using the clinically employed couch shifts, and
alternating day IGRT. The doses delivered to the clinical target volumes are
within approximately 3.2, 1.3, and 2.1% of the plan for the non-IGRT, daily, and
alternating day IGRT protocols, respectively. Doses to relevant portions of the
organs at risk deviate from the plan by up to 10.5, 13.1 and 10.7% for non-IGRT,
daily IGRT, and alternating day IGRT protocols, respectively. Some cases do not
differ significantly between IGRT and non-IGRT protocols in terms of cumulative
DVHs, highlighting the difficult task of correcting prostate bed deformations via
the treatment couch translations. In general, the alternating day IGRT protocol
was found to result in a clinically insignificant deviation in delivered dose
while providing a significant reduction in resource use and patient imaging dose.
PMID- 28516683
TI - Poster - Thur Eve - 57: Craniospinal irradiation with jagged-junction IMRT
approach without beam edge matching for field junctions.
AB - PURPOSE: Craniospinal irradiation were traditionally treated the central nervous
system using two or three adjacent field sets. A intensity-modulated radiotherapy
(IMRT) plan (Jagged-Junction IMRT) which overcomes problems associated with field
junctions and beam edge matching, improves planning and treatment setup
efficiencies with homogenous target dose distribution was developed. METHODS AND
MATERIALS: Jagged-Junction IMRT was retrospectively planned on three patients
with prescription of 36 Gy in 20 fractions and compared to conventional treatment
plans. Planning target volume (PTV) included the whole brain and spinal canal to
the S3 vertebral level. The plan employed three field sets, each with a unique
isocentre. One field set with seven fields treated the cranium. Two field sets
treated the spine, each set using three fields. Fields from adjacent sets were
overlapped and the optimization process smoothly integrated the dose inside the
overlapped junction. RESULTS: For the Jagged-Junction IMRT plans vs conventional
technique, average homogeneity index equaled 0.08+/-0.01 vs 0.12+/-0.02, and
conformity number equaled 0.79+/-0.01 vs 0.47+/-0.12. The 95% isodose surface
covered (99.5+/-0.3)% of the PTV vs (98.1+/-2.0)%. Both Jagged-Junction IMRT
plans and the conventional plans had good sparing of the organs at risk.
CONCLUSIONS: Jagged-Junction IMRT planning provided good dose homogeneity and
conformity to the target while maintaining a low dose to the organs at risk.
Jagged-Junction IMRT optimization smoothly distributed dose in the junction
between field sets. Since there was no beam matching, this treatment technique is
less likely to produce hot or cold spots at the junction in contrast to
conventional techniques.
PMID- 28516685
TI - Poster - Thur Eve - 39: SBRT imaging analysis - patient results and QA of imaging
systems.
AB - Our centre began offering stereotactic body radiation therapy (SBRT) treatments
for peripheral lung lesions in 2011. As a high-precision technique, SBRT requires
precise positioning of the target, and precise quality assurance (QA) of the
imaging systems; these may be dependent on local equipment and procedures. We
aimed to maintain target position within 3 mm throughout each treatment, and
imaging and mechanical systems to at least 2 mm accuracy. A retrospective
analysis was done of patient cone-beam (CB) data, and of our imaging system QA,
to assess our spatial objectives and look for opportunities for improvement. The
data indicated that, using our immobilization and imaging procedures, target
position was maintained within 3 mm 96% of the time, and 75% within 2 mm, similar
to results from other centres. Imaging system QA using the standard ball-bearing
test showed system accuracy was maintained well within 1 mm. These results were
compared with a simpler daily QA procedure using a Pentaguide phantom. The mean
and standard deviation of the radial difference in the kV-MV isocenter
coincidence for the two techniques was 0.62mm +/- 0.23mm. With appropriate choice
of tolerance and action level, the morning QA was sufficient for identifying
outliers requiring further investigation. This analysis gives us confidence in
understanding the performance of our SBRT lung treatments, and gives baselines
for analyzing changes to patient immobilization or imaging procedures.
PMID- 28516686
TI - Poster - Thur Eve - 50: Planning and delivery accuracy of stereotactic
radiosurgery with Tomotherapy as compared to linear-accelerator and robotic based
radiosurgery.
AB - This study includes planning and delivery comparison of three stereotactic
radiosurgery techniques : Helical Tomotherapy (HT), circular collimator-based
Linear-accelerator and robotic-radiosurgery. Plans were generated for two
spherical targets of diameter 6 mm and 10 mm contoured at the center of a Lucite
phantom, using similar planning constrains. Planning comparison showed that
average conformality (0-1best) for Linear-accelerator, robotic-radiosurgery and
HT was 1.43, 1.24, and 1.77 and gradient index (less is better) was 2.72, 4.50
and 13.56 respectively. For delivery comparison, plans were delivered to
radiochromic film and measured dose was compared with the planned dose. For
Linear-accelerator and robotic-radiosurgery more than 99% pixels-passing a gamma
criteria of 3% dose difference and 1 mm distance to agreement where as for HT
this value was as low as 40% for off-axis targets. Further investigation of the
delivery accuracy as a function of the location of the target with in the bore
was initiated using small volume A1SL (0.057 cm3 ) and MicroLion liquid ion
chamber (0.0017 cm3 ). Point dose measurements for targets located at the center
and 10 cm away from the center of the bore showed that delivered dose varied by
more than 15% for targets placed away from the center of the bore as opposed to
at the center. In conclusion, Linear-accelerator and the robotic-radiosurgery
techniques showed preferable gradient and conformality. For HT, point dose
measurements were significantly lower than predicted by the TPS when the target
was positioned away from the isocenter, while they were found to be higher at
isocenter.
PMID- 28516687
TI - Poster - Thur Eve - 21: ROC analysis in patient specific quality assurance.
AB - INTRODUCTION: Many institutions rely on a patient specific measurement for
IMRT/VMAT patient QA. In diagnostic imaging, radiologists use Receiver Operator
Curves (ROC) to help quantify the value of a diagnostic imaging test. The purpose
of this work is to investigate the value or ROC methodology for patient specific
IMRT QA. METHODS AND MATERIALS: Beam fluences for 34 prostate IMRT patients were
analyzed using gamma analysis. For half of these, measurements were done using
the planned beam fluences. For the rest, perturbations to the MLC leaf positions
were introduced. Gamma analysis was then used to measure fluence differences.
Assuming that the unperturbed fluencies were positive measurements, distributions
of true positive and false negatives were calculated. RESULTS: For poorly
performing beam delivery systems the choice of gamma-DTA criterion has little
effect on test sensitivity and specificity. The AUC is increased by about 10% for
high performance beam delivery systems. For a 3%/3mm gamma-DTA condition, ideal
cut off values are reasonably independent of MLC performance. At a tighter gamma
DTA condition of 2%/2mm, then the optimal sensitivity and specificity of the test
is more dependent on MLC performance. DISCUSSION: For a pass-fail test such as
the gamma-DTA map is, it is important to choose an optimal cut off value to
maximize the sensitivity and specificity of the test. ROC methodology allows
users to follow a prescriptive method to obtain ideal cut-off values for gamma
analysis, and to assess improvements in sensitivity and specificity for higher
performing beam delivery system.
PMID- 28516688
TI - Poster - Thur Eve - 61: A dosimetric comparison between single-arc and double-arc
prostate VMAT plans.
AB - This study compared the dosimetry between prostate plans using the single-arc and
double-arc technique in volumetric modulated arc therapy (VMAT). Single-arc and
double-arc prostate VMAT plans were created in five patients with prostate
volumes ranging from 39.0-68.1 cm3 . 6 MV photon beams generated by a Varian 21EX
linac with 120-leaf multileaf collimator, and prescription dose of 78 Gy with 39
fractions were used. Dose-volume histograms of the target and critical organs,
dose criteria such as the planning target volume (PTV) D99%, rectum D30% and
rectum D50%, and dose profiles along the anterior-posterior and lateral
directions crossing the isocenter were determined using the Eclipse treatment
planning system with RapidArc optimization. It is found that the double-arc
technique provided a better PTV coverage and rectal sparing compared to the
single-arc for all patients. For dose profiles crossing the isocenter, it is seen
that the dose in the anterior-posterior direction was shifted to the lateral,
when the single-arc technique was replaced by the double-arc. This dosimetric
change made the dose in the rectal position shift laterally to the femoral head,
resulting in a lower rectal dose. The calculated monitor units (MUs) were 471-600
for the single-arc plans and 587-730 for the double-arc. Although the double-arc
plans on average required more MUs of about 20%, and almost twice the treatment
time compared to the single-arc, it is worthwhile to be considered particularly
in some cases, where the dose criteria are difficult to achieve using the single
arc technique.
PMID- 28516689
TI - Poster - Thur Eve - 52: Clinical use of nanoDots: In-vivo dosimetry and treatment
validation for stereotactic targets with VMAT techniques.
AB - A newly acquired nanoDot In-Light system was compared with TLD-100 dosimeters to
confirm the treatment dose in the multiple cases: an electron eye treatment, H&N
IMRT and VMAT validation for small targets. Eye tumour treatment with 9 MeV
electrons A dose of 1.8 Gy per fraction was prescribed to the 85% isodose. The
average dose measured by three TLDs and three Dots was 1.90 and 1.97 Gy. Both
detectors overestimated dose, by 2.9% and 6.7% respectively. H&N IMRT treatment
of skin cancer with 6 MV photons Dose per fraction is 2.5 Gy. The average doses
measured by two TLDs and two Dots were 2.48 and 2.56 Gy, which represent errors
of -0.8% and 2.2%, respectively. VMAT validation for small targets using an
Agarose phantom, dose 15 Gy A single-tumour brain treatment was delivered using
two coplanar arcs to an Agarise phantom containing a large plastic insert holding
3 nanoDots and 4 TLDs. The difference between the average Pinnacle dose and the
average dose of the corresponding detectors was -0.6% for Dots and -1.7% for
TLDs. A two-tumour brain treatment was delivered using three non-coplanar arcs.
Small and large plastic inserts separated by 5 cm were used to validate the dose.
The difference between the average Pinnacle dose and the average dose of the
corresponding detectors was the following; small phantom 0.7% for Dots and 0.3%
for TLDs, large phantom-1.9% for Dots and -0.6% for TLDs. In conclusion, nanoDot
detectors are suitable for in-vivo dosimetry with photon and electron beams.
PMID- 28516690
TI - Poster - Thur Eve - 23: Statistical analysis and verification of the percentage
depth dose calculation based on the tissue maximum ratio in external beam
radiotherapy.
AB - The aim of this study is to perform a statistical analysis to verify the
calculated percentage depth dose (PDD) based on the tissue maximum ratio (TMR)
with the PDD measurements taken in water. 6 and 15 MV photon beams produced by a
Varian linear 2100 C/D accelerator were used. PDDs and TMRs were measured at
various depths and field sizes (5 * 5, 10 * 10, 15 * 15, 20 * 20 and 30 * 30 cm2
) using a PTW 31006 ionization chamber and a scanning water tank. By comparing
the calculated and measured PDD results, it was seen that for larger field sizes
the deviation between the calculated and measured PDD was smaller. Deviations
between the calculated and measured results were found to be higher in the build
up regions of the 6 and 15 MV photon beams. For the statistical analyses, t-tests
were performed using the measured and calculated PDDs for each field size but
showed insignificant deviations for the 6 and 15 MV photon beams. The mean t-test
values are 0.952 and 0.970 for the 6 and 15 MV photon beams, respectively. The
difference between the calculated and measured PDD is within the acceptable range
according to the ICRU reports (ICRU Report No. 24, 1976). We conclude that
accurate calculation of the PDD using the measured TMR data is possible, which is
useful as the PDD cannot be measured directly.
PMID- 28516691
TI - Poster - Thur Eve - 63: Dosimetric impact of breathing motion in lung SBRT: Dual
vs single volumetric modulated arc therapy.
AB - Volumetric modulated arc therapy (VMAT) is a time efficient treatment delivery
platform capable of producing highly conformal dose distributions with a single
360 degrees arc. However, additional arcs can be used to further improve the
conformal dose distribution. For these reasons, VMAT is often used for
stereotactic body radiation therapy (SBRT) in which the treatment deliveries are
hypofractionated. The dosimetric impact of tumour motion, especially in lung SBRT
where tumour motion is most significant and treatments are hypofractionated, has
always been a clinical concern. Through the use of 4-dimensional computed
tomography (4D-CT), 4D dose distributions can be calculated that account for
dosimetric errors due to motion and temporal variation in lung density that are
not accounted for in clinical treatment plans. The purpose of this study was to
quantify the dosimetric differences that arise due to tumour motion and
variations in lung density between single and dual VMAT SBRT treatment plans. Six
patients previously treated for stage I/II non-small-cell lung cancer with SBRT
were included in this retrospective study. 3D and 4D dose distributions were
calculated for both single and dual arc plans for each of the six patients. Dose
volume histogram metrics are reported for the target and critical structures. The
results show significant differences (p <= 0.05) between the 3D and 4D dose
distributions for the ratio of the prescription isodose volume to the primary
target volume (PTV). This result was consistent for both single and dual arc VMAT
plans.
PMID- 28516692
TI - Poster - Thur Eve - 34: Evaluation of 4DCT on the GE lightspeed RT16 using a
respiratory motion phantom.
AB - PURPOSE: This study encompasses several quality assurance tests performed during
the commissioning of the 4DCT technique on the GE Lightspeed RT16 CT scanner for
SBRT at the Cancer Centre of Southeastern Ontario. The main purpose is to assess
geometric position and volumetric delineation accuracy. A limited assessment of
the image quality and dose was performed. METHODS: The Quasar Respiratory Motion
with a modified cylindrical moving insert was used. Clinically relevant breathing
motion patterns analyzed were: sinusoidal with amplitudes of 5 and 15 mm, and
periods of 3 s and 6 s; and a typical respiratory breathing motion of amplitude
of 10 mm and period of 4 s. RESULTS: Couch position errors were <= 1mm for
maximum inspiration (Ph 0%) and expiration (Ph 50%) phases. errors were greater
for mid-phases, the largest being 8.1 mm (Ph 20%) for the typical respiratory
pattern. MIP volume deviations ranged from -0.3 to -3.2 cm3 ; the greater
deviations corresponding to larger amplitudes and shorter periods, where image
distortion is also more severe. SUP and INF position error of MIP on coronal
views for the lung window and level used in our centre ranged from -0.07 to 1.4
mm and from -0.04 to 1 mm on the SUP and INF direction respectively. The dose
from a 4DCT acquisition was 2.8 times higher than in a free breading scan, while
the noise was comparable. CONCLUSIONS: Although higher doses are obtained, 4DCT
is a sufficiently accurate approach that could be used safely to account for
breathing motion.
PMID- 28516693
TI - Poster - Thur Eve - 45: Commissioning of the Varian ECLIPSE eMC algorithm for
clinical electron treatment planning.
AB - Fast electron Monte Carlo systems have been developed commercially, and
implemented for clinical practice in radiation therapy clinics. In this work the
Varian eMC (electron Monte Carlo) algorithm was commissioned for clinical
electron beams of energies between 6 MeV and 20 MeV. Beam outputs, PDDs and
profiles were measured for 29 regular and irregular cutouts using the IC-10
(Wellhofer) ionization chamber. Detailed percentage depth dose comparisons showed
that the agreement between measurement and eMC for different characteristic
points on the PDD are generally less than 1 mm and always less than 2 mm, with
the eMC calculated values being lower than the measured values. Of the 145
measured output factors, 19 cases fail a +/-2% agreement but only 8 cases fail a
+/-3% agreement between calculation and measurement. Comparison of central axis
dose distributions for two electron energies (9, and 20 MeV) for a 10 * 10 cm2
field, centrally shielded with Pb of width 0 cm (open), 1, 2 and 3 cm, shows
agreement to within 3% except near the surface. Comparison of central axis dose
distributions for 9 MeV in heterogeneous phantoms including bone and lung inserts
showed agreement of 1 mm and 3 mm respectively with measured TLD data. The
overall agreement between measurement and eMC calculation has enabled us to begin
implementing this calculation model for clinical use.
PMID- 28516694
TI - Poster - Thur Eve - 56: Verification of buildup region dose calculation of a
treatment planning system.
AB - Buildup region dose calculation of Pinnacle3 (version 9.0), a treatment planning
system (TPS) commissioned using cylindrical ionization chamber measurements, have
been verified experimentally. Dose values measured using Attix parallel plate
ionization chamber were compared with those calculated by Pinnacle3 for a variety
of clinical setups involving: 6 MV and 15 MV photon beams, open fields, enhanced
dynamic wedges, physical wedges, block tray, 85, 100 and 120 cm source-to-surface
distances, and square field sizes ranging from 3 * 3 to 30 * 30 cm2 . The dose
difference (DD) and distance-to-agreement (DTA) techniques were used to evaluate
the discrepancy between measured and calculated dose values. Based on the
criteria of DD less than 2% or DTA less than 2mm, 93.7% of 1,710 dose points for
the 6 MV and 96.1% of 2,244 dose points for 15 MV passed. Dose points that failed
were mostly for open fields, block tray fields, and physical wedges (15 and 30
degrees) fields; this is attributed to high electron contamination (EC)
associated with these fields. The levels of discrepancies between measured and
calculated dose values were greatly reduced after remodeling the EC in Pinnacle3
using Attix chamber measurements, an indication that the EC equation in Pinnacle3
may be adequate for modeling EC in the dose buildup region, and the commissioning
of a TPS using cylindrical ionization chamber measurements may not provide
accurate buildup region dose calculation. Attix chamber measurements were
validated using GafChromic EBT2 film; the disagreement was less than 3% for 89.9%
of dose values compared.
PMID- 28516695
TI - Poster - Thur Eve - 27: Scattering foil redesign for modulated electron
radiotherapy.
AB - This work serves to build on existing work that discussed the advantages of
removing the scattering foil from the beamline for modulated electron
radiotherapy (MERT) much like flattening filter-free beams in photon IMRT. Due to
concerns about the ability of the accelerators transmission ionization chamber to
function normally with narrow, minimally-scattered beams as well as a limited
maximum field size, this study focused on the design of a new custom scattering
foil that was optimized for MERT applications. Different foil parameters such as
material, thickness and shape were investigated to produce a minimally scattered
beam, as opposed to a flat beam in the case of the clinical foil, while
preserving the dosimetric benefits of a reduced thickness foil such as
dramatically higher dose rate and reduced photon contamination in the
bremsstrahlung tail. Using a Monte Carlo model that was verified against measured
data, fluence profiles at the level of the transmission ionization chamber were
produced and analyzed for all foil configurations, as well as PDDs and profiles
in a water phantom. It was found that a simple foil of slab geometry made of low
to medium Z material with the thickness determined by the maximum desirable field
size and chosen electron energy produced a sufficiently scattered beam that
maintained the dosimetric advantages of a scattering-foil-free beamline. These
new foils, when applied to MERT, have the advantage of reducing treatment time
due to higher dose rates and reducing dose to healthy tissue due to reduced dose
in the bremsstrahlung tail.
PMID- 28516696
TI - Poster - Thur Eve - 38: Review of couch parameters using an FMEA.
AB - To improve patient safety during positioning, we undertook a systematic review of
the processes used by our center to obtain couch positions. We used a Failure
Mode and Effects Analysis (FMEA) framework and fifteen different possible
failures were identified and rated. The three major failures were 1) Loss of
planned couch position and bias from the previous day's couch position, 2) DICOM
origin or isocenter is different between two plans (imaging or treatment), and 3)
Patient shift in opposite direction than intended. The main effect of these
failures was to cause an override of couch parameters. Based on these results, we
modified our processes, introduced new QA and software checks and developed new
tolerance tables so as to improve system robustness and increase our success rate
at catching failures before they can affect the patient. It has been a year since
we made these modifications. Based on our results, we have reduced the number of
overrides at our center from a maximum of 20.5% to a maximum of 6.3%, with an
average at 4% of daily treatments. Our results suggest that FMEA is an effective
tool in improving treatment quality that could be used in other centers.
PMID- 28516697
TI - Poster - Thur Eve - 49: Application of plastic scintillating detectors to
orthovoltage x-ray measurements.
AB - Plastic scintillating detectors (PSDs) have found numerous dosimetric
applications in radiotherapy due to their approximate water equivalence at high
energies and their small physical size. At low photon energies, however, the
ratio of mass attenuation coefficients (PSD : water) deviates from unity, which
potentially limits their utility in this range. In this work, measurements of
orthovoltage cutout factors were made with PSDs and and ion chamber. Results were
compared to Monte Carlo simulations of the same geometry. Results indicated that
the PSDs performed better than the IC in almost all field sizes. Further work is
required to more thoroughly characterize the Monte Carlo model of the x-ray unit
and to investigate any discrepancies that might have resulted from slight
differences in the effective point of measurement of the two detector systems.
PMID- 28516698
TI - Poster - Thur Eve - 20: Serial FDG 4DPET imaging during radiotherapy in advanced
lung cancer patients.
AB - The availability of respiratory synchronized PET (4DPET) imaging has enabled more
accurate analysis of metabolic response since motion blur is minimized. We
present our preliminary analysis of serial FDG 4DPET images acquired at weeks 0,
2, 4, and 7 during radiotherapy of seven stage II-III NSCLC patients. The tumor
and nodal PTV of the week 0 images restrained a 4DPET image thresholding
algorithm to automatically contour SUV levels ranging from 20 to 80% of the
maximum SUV, creating an intensity volume histogram (IVH) for each week. These
contours allowed analysis of PET volumes and standard PET metrics such as SUVmax
and SUVmean . We found a trend for decreasing SUVmax and SUVmean over a treatment
course in both the tumor and nodal regions. On average, the SUVmax within the
tumor decreased by 17+/-13% (1 SD) after 2 weeks, 30+/-13% after 4 weeks, and
39+/-19% after 7 weeks of radiotherapy. Decreasing volume trends were also
observed in the 20 to 80% max SUV autocontours, ranging from 26+/-29% to 50+/-40%
respectively, over 7 weeks of treatment. Only one patient demonstrated an
increase in FDG uptake within the tumor volume between week 0 and week 2 of
treatment, and was also the only patient to recur locally at 3 months following
treatment. Changes in tumor metabolism over the course of advanced NSCLC
radiotherapy are quantifiable with serial FDG 4DPET imaging. Preliminary analysis
suggests that variations in these trends could be useful in identifying non
responding patients that may require an alternative radiotherapeutic approach.
PMID- 28516699
TI - Poster - Thur Eve - 60: Physical and dynamic wedges in radiotherapy for rectal
cancer: A dosimetric comparison.
AB - The aim of this study is to compare the dosimetry of the physical wedge (PW) and
enhanced dynamic wedge (EDW) in radiotherapy of rectal cancer. Two wedge angles
of 45 degrees and 60 degrees were used in the comparison due to the size of the
pelvis contour. 6 and 15 MV photon beams produced from a Varian 21 CD linear
accelerator were used. Thirty rectum patients were investigated using the three
field technique. Treatment plans using the PWs and EDWs were created using the
Eclipse treatment planning system. Monitor units, plan normalization value,
maximum and minimum doses in the planning target volume (PTV), dose conformity
index, dose homogeneity index and uniformity index were determined for each
treatment plan. The average dose coverage for the PTV with EDW and PW plans were
compared. The PTV received prescription doses of 100.9+/-0.74%, 101.01+/-1.63%
for the EDW (45 degrees , 60 degrees ) compared to 101.2+/-1.65%, 101.3+/-1.33%
for the PW (45 degrees , 60 degrees ). Homogeneity indices were (0.11+/-0.02%,
0.11+/-0.05%) for the EDW (45 degrees , 60 degrees ), and (0.15+/-0.1%, 0.16+/
0.11%) for the PW (45 degrees , 60 degrees ), respectively. The EDW at 45 degrees
had better target coverage with higher conformity index value of 0.98 +/- 0.01
compared to the other wedges. A statistically significant (p < 0.01) change in
plan normalization values and fewer monitor units were found using the EDW at 45
degrees . We conclude that the EDW at 45 degrees results in an improvement to
the plan evaluation parameters presented and thus increases dose efficacy for
radiotherapy of rectal cancer.
PMID- 28516700
TI - Poster - Thur Eve - 31: RapidArc total body photon irradiation: A feasibility
study.
AB - Total body photon irradiation (TBI) may be delivered with a number of standard
techniques, typically using extended SSD geometries to obtain large field sizes.
Since 1982 we have treated over 620 patients (adult and pediatric) mostly in the
floor-located prone/supine treatment position with AP/PA beams using a column
mounted 4 MV linac, and more recently with a fixed field, extended SSD, Cobalt
teletherapy unit. This treatment position has many advantages for TBI including
ease of delivery (especially for pediatric or compromised patients), improved
dose uniformity, simplicity for partial or complete organ shielding, and imaging
capabilities to name a few. In an effort to transfer this technique to a
conventional isocentric linac, we have undertaken a feasibility study for
RapidArc based extended SSD total body irradiation. Proof of principle was first
explored using the DBD (Dynamic Beam Delivery) toolbox to configure a 6 MV beam
with an 80 degree arc, centered on the 12 o'clock gantry angle with a sliding
window beam. This was followed by the development of an ECLIPSE generated 80
degree RapidArc plan. Initial measurements were conducted with a Varian 21EX
using the 6 MV DBD beam to explore characteristics such as PDD, surface dose, off
axis ratios, output, dose per MU, and linearity. Subsequently ECLIPSE generated
RapidArc TBI plans using similar partial arcs were also evaluated. Encouraged by
our results, we believe this technique shows potential for making floor-located
AP/PA total body photon irradiation possible for any standard RapidArc enabled
isocentric linac.
PMID- 28516701
TI - Poster - Thur Eve - 22: Bone heterogeneity in kV x-ray radiotherapy.
AB - This study evaluated the dosimetric impact of bone heterogeneity on the surface
dose and dose prescription, when dose is assumed to be prescribed on a
homogeneous medium in kV x-ray radiotherapy. A heterogeneous phantom containing a
thin water layer (thickness = 1-5 mm) over a bone (thickness =1 cm) was used to
mimic treatment sites of forehead, knee and chest wall. The phantom was
irradiated by a 220 kVp photon beam with field size of 5 cm diameter. Percentage
depth dose, surface dose and photon energy spectrum with different thicknesses of
water were determined using Monte Carlo simulations (the EGSnrc code) with
experimental verifications using parallel-plate ionization chamber and
radiochormatic film. Our results (treatment cone of 5 cm diameter) showed that
the surface dose increased in a range of 2.5-3.7% when the water layer above the
bone was increased from 1 to 5 mm. However, the surface dose did not increase
linearly with the increase of water thickness, and the maximum increase of
surface dose was found at a water thickness of 3 mm. Results of the percentage
depth dose showed that the maximum bone dose was about 210% higher than the
surface dose in the heterogeneous phantom. It is concluded that in treatment
sites having a thin layer of tissue over a bone in kV x-ray radiotherapy, if
increased surface dose due to bone heterogeneity is not considered, this will
result in an additional dosimetric uncertainty narrowing down the total error
margin (5%).
PMID- 28516702
TI - Poster - Thur Eve - 62: Assessing the clinical application of the van Herk margin
formula for lung radiotherapy.
AB - According to a margin recipe developed by van Herk et al. the Planning Target
Volume (PTV) margin to ensure the Clinical Target Volume is covered by at least
95% of the prescribed dose can be calculated by applying the following formula: M
= 2.5Sigma + 1.64sigma2 - 1.64sigmap. In the van Herk Margin formula (VHMF),
Sigma is the standard deviation (SD) of all systematic errors; sigma is the SD of
random errors and sigmap is the width of the penumbra. This formula is based on
an idealized dose profile model that may not account for factors that vary
significantly in lung radiotherapy such as tumour size and tissue density. The
purpose of this study was to use accurate dose calculation algorithms and
respiratory motion modeling to investigate the validity of the VHMF for lung
radiotherapy. Random and systematic errors were simulated in treatment planning
software using dose accumulation techniques for clinically relevant 3DCRT and
IMRT treatment plans constructed on virtual phantoms. Phantom parameters such as
target size, peak-to-peak motion amplitude and tissue density were varied to
investigate their impact on the systematic and random error components of the
margin formula. The VHMF was found to provide adequate dose coverage for all
plans generated on different target sizes and motion amplitudes. Although
discrepancies existed between idealized and realistic dose profiles in water and
lung, the dose coverage defined by the V95 was not affected. The margin formula
was found to be robust; however, further investigation of the influence of plan
conformity is needed.
PMID- 28516703
TI - Poster - Thur Eve - 33: A comprehensive analysis of the effect of respiratory
motion on the delivery of IMRT to advanced stage non-small cell lung cancer.
AB - The goal of this work was to quantify the interplay effect of various IMRT
delivery techniques in the treatment of Stage III non-small cell lung cancer.
Five patients with significant tumour motion were retrospectively planned on the
average 4D-CT dataset with eight different IMRT techniques: three Tomotherapy
techniques with different beam-widths, two step-and-shoot (SS-IMRT) with
different complexity, one sliding-window (SW-IMRT), and two VMAT techniques
(RapidArc and SmartArc). Each plan was calculated on a delivery verification
phantom that was mounted on a programmable respiratory motion platform and
delivered under the following motion conditions: 1) Static; 2) sinusoidal with 4
different amplitudes; 3) Real Patient Breathing. A standard 3%/3mm gamma analysis
compared the sum of all 30 fractions to their corresponding 60Gy/30fx plan. One
way ANOVA was conducted for respiratory motion amplitude and IMRT modality,
separately. There were no significant differences amongst the modalities at any
amplitude level. However, for individual modalities, there were significant
differences amongst different amplitudes except for Tomo-2.5cm (p=0.260). Post
hoc Tukey tests determined that detectable significant differences amongst any
motion level, including real-patient breathing, were observed when compared to
the 20mm amplitude for all modalities except Tomo-2.5cm and SmartArc. SW-IMRT
showed significant differences at 15mm when compared to both static (p=0.033) and
5mm (p=0.008). All methods except for RapidArc averaged out to clinically
acceptable gamma pass rates up to 15mm. In conclusion, for motion levels above
15mm, the interplay effect can be clinically unacceptable. However, the interplay
effect at these motion levels does not appear to be modality dependent.
PMID- 28516704
TI - Poster - Thur Eve - 44: Digital tomosynthesis image quality in a Co-60 treatment
beam.
AB - Image guidance capability is an important feature of modern radiotherapy
machines. Cobalt-60 units will require some form of image guidance if they are to
be brought up to modern standards. Imaging in the treatment beam is an appealing
option, for reasons of simplicity and cost, but the dose needed to produce cone
beam CT images in a Co-60 treatment beam is too high for this modality to be
clinically useful. Digital tomosynthesis (DT) offers a quasi-3D image, of
sufficient quality to identify bony anatomy or fiducial markers, while delivering
a much lower dose than CBCT. A series of experiments were conducted on a
prototype Co-60 cone beam imaging system to quantify the resolution, selectivity,
geometric accuracy and contrast sensitivity of Co-60 DT. Although the resolution
was severely limited by the penumbra cast by the ~2cm diameter source, it was
possible to identify high contrast objects on the order of 1 mm in width, and
bony anatomy in anthropomorphic phantoms was clearly recognizable. Low contrast
sensitivity down to electron density differences of 3% was obtained, for uniform
features of similar thickness. The conventional shift-and-add algorithm was
compared to the FDK filtered backprojection algorithm using several different
spatial filters. The Co-60 DT images were obtained with a total dose of 5 to 15
cGy. We conclude that, should Co-60 radiotherapy units be upgraded with image
guidance capabilities, filtered backprojection DT in the treatment beam is a
versatile and promising modality that would be well suited to the task of patient
positioning.
PMID- 28516706
TI - Poster - Thur Eve - 26: Interfraction reproducibility of heart position during
breast irradiation using Active Breathing Control.
AB - The moderate deep-inspiration breath hold (mDIBH) technique using the Active
Breathing Coordinator (ABC) from Elekta is used in our clinic to lower the heart
dose during left breast irradiations. The purpose of this work was to investigate
the interfraction reproducibility of the heart to chest distance during these
treatments and to evaluate the dosimetric effect of any changes in the heart
position. Daily CBCT images were available for 5 patients who had been treated
with ABC tangents and a cavity boost. On these images, one-dimensional
measurements of the distance between the heart and the chest wall were taken at
two anatomical locations corresponding roughly with the location where the
radiation field most likely intercepts the heart. The average change in this
distance was interpreted as a shift of the heart position. To assess the effect
of this shift on the delivered heart dose, the heart contours in the clinical
plans of the corresponding patients were shifted towards the treatment field
using standard Pinnacle tools. Although the ABC device allows good
reproducibility of the volume of air held, this does not warrant reproducibility
of heart position for all patients during treatment. The largest average heart
shift extracted from CBCT images in this study was 6.2mm. The heart dose
reconstructed using this shift for the corresponding patient also showed the
largest effect. However, even in the presence of a systematic heart shift of this
magnitude, the ABC plan still showed superior heart dose reduction compared to
the free-breathing plan.
PMID- 28516705
TI - Poster - Thur Eve - 55: Monte Carlo simulations of variations in planned dose
distributions in a prostate patient population.
AB - Clinical outcome studies with clear and objective endpoints are necessary to make
informed radiotherapy treatment decisions. Commonly, clinical outcomes are
established after lengthy and costly clinical trials are performed and the data
are analyzed and published. One the challenges with obtaining meaningful data
from clinical trials is that by the time the information gets to the medical
profession the results may be less clinically relevant than when the trial began,
An alternative approach is to estimate clinical outcomes through patient
population modeling. We are developing a mathematical tool that uses Monte Carlo
techniques to simulate variations in planned and delivered dose distributions of
prostate patients receiving radiotherapy. Ultimately, our simulation will
calculate a distribution of Tumor Control Probabilities (TCPs) for a population
of patients treated under a given protocol. Such distributions can serve as a
metric for comparing different treatment modalities, planning and setup
approaches, and machine parameter settings or tolerances with respect to outcomes
on broad patient populations. It may also help researchers understand differences
one might expect to find before actually doing the clinical trial. As a first
step and for the focus of this abstract we wanted to see if we could answer the
question: "Can a population of dose distributions of prostate patients be
accurately modeled by a set of randomly generated Gaussian functions?" Our
results have demonstrated that using a set of randomly generated Gaussian
functions can simulate a distribution of prostate patients.
PMID- 28516708
TI - Poster - Thur Eve - 48: An inexpensive and convenient phantom for quality
assurance in image guidance based radiosurgery.
AB - This work describes the design and use of an inexpensive phantom designed for
precision measurements in radiosurgery quality assurance. The main features of
this simple phantom include its solid water construction, interchangeable ion
chamber holders and film registration system, thus allowing for measurement of
small fields with several detectors using the same phantom. The entire phantom
was constructed using one 30cm * 30cm * 3cm slab of solid water. The phantom
contains a slot that allows for the placement of two small volume ion chambers
(liquid and A1SL) via custom inserts near the center of the phantom. In addition,
the plug can be filled for film measurements. The phantom can be split down the
center to allow for the placement of a film. As opposed to registering film to
room based markers, such as lasers, the phantom contains radio-opaque fiducials
that puncture the film while also providing a method to register the film images
to exported dose planes. In addition to the markers used for film registration,
the phantom contains several external beebees that can be used to avoid ambiguity
in image registration when using image guidance for setup. This simple phantom
contains many features of other much more expensive phantoms designed for this
purpose and has been found to be very useful clinically and in departmental
research. The key elements of this phantom could be included in several other
designs allowing it to be reproduced in other centers.
PMID- 28516707
TI - Poster - Thur Eve - 37: Improved clustering MLC leaf-sequencing algorithm for
step-and-shoot IMRT.
AB - This study examines how to reduce the complexity of fluence map generated using
an improved clustering leaf-sequencing method, and evaluates such method in step
and-shoot intensity-modulated radiotherapy (IMRT). Based on the current equal
space grouping algorithm for multileaf collimator (MLC) leaf sequence, we
proposed an improved K-means grouping algorithm which can replace the
stratification routine in the program of existing leaf sequence. The improved
algorithm can be thought of as a gradient descent procedure, which begins at
starting cluster centroids, and iteratively updates these centroids to decrease
the objective function. The K-means always converge to a local minimum depending
on the starting cluster centroids. The K-means algorithm continuously updates
cluster centroids until the local minimum is reached. We compare the leaf
sequencing results in term of numerical values from the improved K-means and
equal-space grouping algorithm. A representative 1D intensity map from a clinical
treatment plan was investigated and optimized by the K-means and equal-space
grouping algorithm. It was found that the K-means algorithm decreased the dose
square error from 53.67 to 35.27. Moreover, the normalized square differences of
the equal-space and K-means algorithm are equal to 2881 and 1244, respectively.
The results demonstrated an improvement in accuracy achievable by allowing the
fluence map to be defined in an optimal way rather than using the pre-defined
criteria. Therefore, the K-means leaf-sequencing algorithm can better simulate
the distributions of the input fluence data compared to the traditional grouping
algorithm in step-and-shoot IMRT.
PMID- 28516709
TI - Poster - Thur Eve - 19: Risk assessment of clinical radiation processes using
failure modes and effect analysis.
AB - The aim of this work was to apply failure modes and effect analysis (FMEA) to
assess risk in two radiation planning and treatment processes; our on-call (out
of-clinical hours) process and our tomotherapy process. The motivation was
provided by analysis of 2506 adverse incidents reported over a 5 year period, the
on-call process for giving rise to a higher than expected number of incidents and
our tomotherapy process for the reverse. For the on-call scenario, three separate
processes were analysed: our current process, our current process incorporating a
software upgrade eliminating several planning steps and a fully integrated
process in which the patient is imaged, planned and treated on a single platform
(TomoTherapy Hi Art, Accuray Incorporated, Sunnyvale, CA). After construction of
a detailed process map for each case, a multidisciplinary group identified
potential failure modes for each process step, the effects of each failure and
existing controls. Risk probability numbers were determined from severity,
frequency of occurrence and detectability scores assigned to each failure mode
according to a standard scale. The results were analysed to identify and
prioritise feasible and effective process improvements. For the on-call process,
our current workflow was identified as incurring the highest risk of the three
processes analysed, demonstrating quantitatively the value of the software
upgrade and providing a clear rationale for the associated expense. In summary,
we have found FMEA to be a feasible tool for assessing relative risk in a
clinical process. However, operational and resource issues must be considered
separately.
PMID- 28516711
TI - Poster - Thur Eve - 30: Comparison of treatment planning and delivery performance
of VMAT versus IMRT.
AB - The purpose of this study was to determine whether VMAT (Varian RapidArc TM)
treatment planning and delivery performance is in compliance with accepted
quality assurance tolerances developed for sliding window IMRT. We present an
analysis of data for over 1300 patients treated with VMAT and IMRT over a period
of three years. Data was acquired on 6 dosimetrically matched linacs for sites
including head and neck, brain, gynaecological, and a variety of other cancer
cases treated with 6 MV. We have demonstrated that it is possible to
dosimetrically match multiple Varian iX linacs with the millennium series MLC
using a sliding gap and intercept test. QA is performed by Monte Carlo simulation
and ion chamber measurement comparisons with Varian Eclipse TPS as well as linac
log file analysis of MLC positions, gantry angles and monitor units on each
patient. Point dose and 3D gamma analysis indicate that agreement between Eclipse
and measurement or Monte Carlo calculation is site specific, with the dosimetric
leaf gap parameter in Eclipse optimized for the most frequently treated site
Point dose agreement within 2% and gamma pass rate of > 95% (3%/ 3 mm) is
achievable for all sites for both IMRT and VMAT. Linac log file analysis
indicates that planned MLC positions are achieved within 2 mm >99.7% of the time
for both sliding window IMRT and VMAT. Planned gantry angles are achieved within
0.6 mm 99.8% of the time and planned MU's within 0.1 mm are achieved 99.8% of the
time for VMAT.
PMID- 28516710
TI - Poster - Thur Eve - 59: Dosimetric evaluation on the variation of PTV coverage
due to patient size reduction using the prostate dose-volume factor in prostate
radiotherapy.
AB - We proposed to use the prostate dose-volume factor (PDVF), derived from the dose
volume dataset of planning target volume (PTV) in prostate radiotherapy to
evaluate treatment plans of prostate volumetric modulated arc therapy (VMAT) and
intensity modulated radiotherapy (IMRT). To demonstrate plan evaluation using
PDVF, VMAT and 7-beam IMRT plans were created in three patients with prostate
volumes equal to 32, 48.4 and 86.5 cm3 . Dose variation of PTV was made by
reducing the body contour of the patients with reduced depth equal to 0.5 - 2 cm,
mimicking a patient size reduction in the treatment. The Gaussian error function
was used to model the cumulative dose-volume histogram of the PTV, and PDVF was
calculated as per the parameters of the error function. PDVF = 1 reflects an
ideal PTV coverage (i.e. 100% prescribed dose in 100% target volume). We found
that for PDVF ranged 0.98 - 1 in prostate VMAT and IMRT without patient size
change, reduced depth led to PDVF decreasing 0.03 +/- 4.7 * 10-4 (VMAT) and 0.04
+/- 9.7 * 10-3 (IMRT) per cm for the patients. The variation of PTV coverage on
the prostate volume due to the reduced depth was less significant in VMAT plans
than IMRT. It is concluded that PDVF was successfully used to evaluate the
variation of PTV coverage due to the weight loss of patient in prostate VMAT and
IMRT. Degradation of PTV coverage in prostate VMAT regarding patient size
reduction is less significant than that in IMRT.
PMID- 28516712
TI - Poster - Thur Eve - 41: Effect of beam symmetry on enhanced dynamic wedge quality
assurance and tolerance levels.
AB - Wedged fields are common in three dimensional conformal radiation therapy and
require appropriate quality assurance (QA). Currently, our centre calculates the
angle of enhanced dynamic wedge (EDW) deliveries with the PROFILER at a monthly
frequency but Canadian guidelines on the recommended QA of enhanced dynamic
wedges are not available yet. TG-142 recommendations include monthly validation
of the central axis wedge factors with only annual verification of wedge
profiles. Our monthly QA results have demonstrated a sensitivity of the
calculated EDW angle to open beam symmetry. The goal of this work is to compare
wedge angle and direct profile comparison as QA measures of EDW delivery and
determine appropriate parameter tolerances. The impact of open field symmetry
variations on EDW profiles was determined by varying beam symmetry with a test
potentiometer and measuring the resulting EDW beam profile with the PROFILER. A
calculated wedge angle and direct profile comparison were used to describe the
deviations in EDW deliveries. The impact of the deviations on typical plans
incorporating wedged fields was evaluated by constructing 'equivalent wedges' to
the profile deviations using mixed 60 degree and open field beams and performing
plan comparisons in Eclipse. Beam symmetry was observed to have a significant
impact on wedge angle for small angle wedges, with a 1% symmetry tolerance
allowing a 3.4 degree range of wedge angles for a nominal 10 degree wedge. Direct
profile comparison allows a more consistent definition of a dose based tolerance
range to be applied without angle dependent tolerances.
PMID- 28516713
TI - Poster - Thur Eve - 32: Water tank referenced calibration method for detector
array devices.
AB - INTRODUCTION: Detector array devices, such as the I'mRT Matrixx (IBA Dosimetry),
provide a means of evaluating beam profiles with respect to gantry for a range of
dose rates and monitor units. The relative calibration of these devices is
typically highly susceptible to even relatively small variations in beam output.
An alternative method is proposed here, which directly references the device
detector response to water tank data. METHODS: The Matrixx response was measured
at the four cardinal angles for three devices. A calibration factor was
determined for each orientation of the Matrixx device by dividing a water tank
measured profile by the Matrixx response for the in-plane and cross-plane
detectors. A geometric mean of each orientation was used as the estimate of the
calibration coefficient. RESULTS: Before calibration, the three-detector average
of the deviation from the profile measured in the water tank centered on each of
the horns was 0.4% (SD 0.2%); applying the calibration procedure reduced this to
0.1% (SD 0.1%). The energy independence of the proposed relative calibration was
also confirmed. A comparison of the linac output for relatively short Matrixx
acquisitions to the longer water tank acquisition suggested some difference. This
difference was mitigated by averaging. CONCLUSIONS: The proposed water tank
reference calibration procedure is an effective means of determining the relative
calibration of a detector array and mitigates the effect of compound error by
avoiding the recursive algorithm of typical calibration methods. In addition it
has the benefit of being directly relatable to commissioning beam data.
PMID- 28516714
TI - Poster - Thur Eve - 43: Is faster always better? An evaluation of frame rate
effects on continuous acquisition mode EPID imaging for dose verification.
AB - INTRODUCTION: As radiotherapy moves towards intensity modulated arc therapy (arc
IMRT), there is a need for electronic portal imaging (EPID) to move towards
continuous acquisition (cine) mode for dosimetric verification purposes. However,
as the EPID resolution and frame rate (fps) increase, so does the computational
burden of image processing. We investigated the reliability of cine mode EPID
imaging in IMRT as a function of frame rate. METHODS: We acquired EPID images
continuously while running an IMRT plan (6MV photons, 150MU, dose rate =
300MU/min) with frame rates ranging from 1-12 fps, as well as a single integrated
mode image. Each cine dataset was then averaged to form a single image, which was
compared with the integrated mode image by means of a pixel-by-pixel absolute
value subtraction. RESULTS: Although a greater frame rate gave better agreement
with the integrated mode image in all cases, the relative benefit diminished with
increasing frame rate. In particular, for the IMRT plan delivered, there was
little benefit of imaging faster than 6 fps, and virtually no benefit in
increasing from 9 to 12 fps. In contrast, 12 fps produces twice the number of
images as 6 fps which significantly increases the image processing and data
storage burdens. CONCLUSION: Increasing frame rate in cine mode EPID imaging may
be beneficial in some cases, but there is likely a threshold level above which no
relevant additional information is obtained. Further research to determine the
ideal frame rate for any particular IMRT or arc-IMRT plan is warranted.
PMID- 28516715
TI - Poster - Thur Eve - 54: A software solution for ongoing DVH quality assurance in
radiation therapy.
AB - PURPOSE: A program has been developed in MATLAB for use in quality assurance of
treatment planning of radiation therapy. It analyzes patient DVH files and
compiles dose volume data for review, trending, comparison and analysis. MATERIAL
AND METHODS: Patient DVH files are exported from the Eclipse treatment planning
system and saved according to treatment sites and date. Currently analysis is
available for 4 treatment sites; Prostate, Prostate Bed, Lung, and Upper GI, with
two functions for data report and analysis: patient-specific and organ-specific.
The patient-specific function loads one patient DVH file and reports the user
specified dose volume data of organs and targets. These data can be compiled to
an external file for a third party analysis. The organ-specific function extracts
a requested dose volume of an organ from the DVH files of a patient group and
reports the statistics over this population. A graphical user interface is
utilized to select clinical sites, function and structures, and input user's
requests. RESULTS: We have implemented this program in planning quality assurance
at our center. The program has tracked the dosimetric improvement in GU sites
after VMAT was implemented clinically. It has generated dose volume statistics
for different groups of patients associated with technique or time range.
CONCLUSION: This program allows reporting and statistical analysis of DVH files.
It is an efficient tool for the planning quality control in radiation therapy.
PMID- 28516717
TI - Poster - Thur Eve - 65: Optimization of an automatic image contouring system for
radiation therapy.
AB - Intensity modulated radiation therapy (IMRT) is an advanced technique used to
concentrate the prescribed dose in the tumour while minimizing exposure to
healthy tissues. Success in IMRT is greatly dependent upon the localization of
the target volume and normal tissue, thus accurate contouring is crucial. In this
paper, we describe an automated atlas-based image contouring system and our
approach for improving the system by performing a full-scale optimization of
registration parameters using high-performance computing. To achieve this, we use
manually pre-contoured CT images of ten head and neck patients. For any parameter
set, each patient data is registered with the remaining patients. Accuracy of the
resulting contours is determined automatically by comparing their overlap with
manually defined targets using Dice's similarity coefficient (DSC). This allows
us to compare all permutations of the image registration parameter sets and input
data to investigate their impact on final contour accuracy. Investigating the
parameter space required 27,000 image registrations and 216,000 DSC computations.
To perform these registrations we introduced a large cluster of high-performance
computers and developed a parallel testing harness. The metrics collected from
the tests show a wide range of performance, indicating that parameter selection
is crucial in our contouring system. By selecting an optimized parameter set, we
increased the mean overlap of the automatically contoured regions of interest by
50% and reduced registration time by 50% compared to the original parameters. Our
findings illustrate that full-scale optimization is an effective method for
improving the performance of the automated image contouring system.
PMID- 28516716
TI - Poster - Thur Eve - 25: In vivo dosimetric verification of intensity-modulated
radiation therapy.
AB - Dosimetric verification of patient treatment plans has become increasingly
important due to the widespread use of complicated delivery techniques. IMRT and
VMAT treatments are typically verified prior to start of the patient's course of
treatment, using a point dose and/or a film measurement. Pre-treatment
verification will not detect patient or machine-related errors; therefore, in
vivo dosimetric verification is the only way to determine if the patient's
treatment was delivered correctly. Portal images were acquired throughout the
course of five prostate and six head-and-neck patient IMRT treatments. The
corresponding predicted images were calculated using a previously developed
portal dose image prediction algorithm, which combines a versatile fluence model
with a patient scatter and EPID dose prediction model. The prostate patient image
agreement was found to vary day-to-day due to rectal gas pockets and the effect
of adjustable support rails on the patient couch. The head-and-neck patient
images were observed to be more consistent daily, but an increased measured dose
was evident at the periphery of the patient, likely due to patient weight loss.
The majority of the fields agreed within 3% and 3 mm for greater than 90% of the
pixels, as established by the chi-comparison. This work demonstrates the changes
in patient anatomy that are detectable with the portal dose image prediction
model. Prior to clinical implementation, the effect of the couch must be
incorporated into the model, the image acquisition must be automatically
scheduled and routine EPID QA must be undertaken to ensure the collection of high
quality EPID images.
PMID- 28516718
TI - Poster - Thur Eve - 36: Out-of-Field dose in craniospinal irradiation.
AB - The risk of radiotherapy induced secondary cancer depends on the integral dose
delivered to the patient where the dose delivered within the radiation field is
accounted for, as well as dose to out-of-field organs from scattered and leakage
radiation. While commercial treatment planning systems allow accurate
determination of in-field dose, they are generally not capable of accurate out-of
field dose prediction. Secondary cancer risk is especially an issue in
craniospinal treatments where involved patients are often children or young
adults. In this work we therefore propose a mathematical model that accurately
predicts out-of-field dose for patients treated by craniospinal irradiation at
the American University of Beirut Medical Center. An anthropomorphic phantom was
imaged, planned and treated, with thermoluminescent dosimeters inserted in the
phantom at in-field and out-of-field locations. The measurements showed that our
treatment planning system calculated accurately (within 2%) dose inside the
field, but did not perform well at points just outside the field edge and
consistently underestimated the dose at points further away from the field edge.
From the out-of-field measured data, a model was developed that predicts out-of
field dose at a point in the patient based on the distance of that point to the
treatment field edge. The developed model is of the double-gaussian type; it
contains parameters that can be tuned to make it applicable in other centers
where linac geometry and treatment techniques may differ.
PMID- 28516719
TI - Poster - Thur Eve - 47: Evaluation of the ArcCHECK device for commissioning and
patient-specific QA.
AB - The most promising method of accurately verifying VMAT treatments is by direct
dose measurement over the three dimensions of irradiated volume. ArcCHECK device
(Sun Nuclear, Melbourne, FL) have the potential to detect delivery errors on the
treatment machine due to mechanical problems resulting from gantry and MLC
motion. The estimation of the dosimetric leaf gap (DLG) parameter for Varian MLC
(Varian Medical Systems, Palo Alto, CA) was attempted using ArcCHECK. Finding the
optimal DLG value for use in TPS requires a measuring device like ArcCHECK to be
employed especially in highly intensity modulated fields. In addition, ArcCHECK
was used to assess the effect of positional error of MLC leaf in a given VMAT
plan. Patient-specific QA tests were performed using the ArcCHECK device. QA
results of patient plans that failed considering portal dosimetry technique were
reassessed with ArcCHECK measurements for IMRT plans. The preliminary test
results and performance of the ArcCHECK device were very encouraging. VMAT plans
for head and neck cases were generated and their delivery was evaluated using
ArcCHECK. Results have shown a success rate greater than 90% in the quality
assurance of individual plans. Optimal DLG value was detected using ArcCHECK.
Also, the device showed enough sensitivity to identify failed QA plans. Moreover,
MLC central leaf pair position offset in a VMAT plan of the order of 1mm was
fairly distinguished by ArcCHECK measurements.
PMID- 28516720
TI - Poster - Thur Eve - 18: Characterization of a camera and LED lightbox imaging
system for radiochromic film dosimetry.
AB - Radiation therapy treatment modalities continue to develop and have become
increasingly complex. With this, dose verification and quality assurance (QA) is
of great importance to ensure that a prescribed dose is accurately and precisely
delivered to a patient. Radiochromic film dosimetry has been adopted as a
convenient option for QA, because it is relatively energy independent, is near
tissue equivalent, and has high spatial resolution. Unfortunately, it is not
always easy to use. In this study, preliminary work towards developing a novel
method of imaging radiochromic film is presented. The setup consists of a camera
mounted vertically above a lightbox containing red LEDs, interfaced with computer
image acquisition software. Imaging results from this system will be compared
with imaging performed using an Epson Expression 10000XL scanner (a device in
common clinical use). The lightbox imaging technique with camera readout is much
faster relative to a flatbed scanner. The film measurements made using the camera
are independent of film orientation, and show reduced artifacts, so that there
are fewer corrections required compared to the use of flatbed scanners. Optical
scatter also appears to be less of an issue with this design than with the flat
bed scanner. While further work needs to be done to optimize the lightbox imaging
system, the lightbox system shows great promise for a rapid, simple, and
orientation independent setup, improving on existing film scanning systems.
PMID- 28516721
TI - Poster - Thur Eve - 58: The clinical significance of couch top modeling in VMAT
and IMRT treatment planning.
AB - In recent years, carbon fibre couch tops have become popular in radiation therapy
with marketed attributes such as high tensile strength, light weight, and
relative radiotranslucence. We have performed a detailed analysis of the iBEAM
evo couch top using two models created in the Pinnacle v9.0 treatment planning
system. The first model is a single ROI, and its thickness and shape was
determined based on attenuation factor measurements in cylindrical phantoms. The
second model is a thin shell made of two ROIs with exact outer dimensions as the
real couch top. The couch top attenuation was found to range from 2% to 6.5% for
a 6 MV beam energy. The two models were found to match the attenuation factor
measurements to within 4.2% and 1.7%, respectively. The clinical impact of the
couch top models was examined in 4 VMAT and 4 IMRT prostate plans by comparing
mean and maximum point doses, DVHs, and measurements (VMAT plans only) using
Gamma analysis. A very small, but clinically insignificant difference was
observed between the two couch top models for both VMAT and IMRT plans. The lack
of a couch top model in treatment planning was also examined and found to result
in ~ 1% average underdose to the PTV. This study suggests that the iBEAM evo
couch top is relatively radiotranslucent for typical VMAT and IMRT delivery as
long as the number of control points with extremely oblique beam angles is
relatively small.
PMID- 28516722
TI - Poster - Thur Eve - 29: Detecting changes in IMRT QA using statistical process
control.
AB - Statistical process control (SPC) methods were used to analyze 239 measurement
based individual IMRT QA events. The selected IMRT QA events were all head and
neck (H&N) cases with 70Gy in 35 fractions, and all prostate cases with 76Gy in
38 fractions planned between March 2009 and 2012. The results were used to
determine if the tolerance limits currently being used for IMRT QA were able to
indicate if the process was under control. The SPC calculations were repeated for
IMRT QA of the same type of cases that were planned after the treatment planning
system was upgraded from Eclipse version 8.1.18 to version 10.0.39. The initial
tolerance limits were found to be acceptable for two of the three metrics tested
prior to the upgrade. After the upgrade to the treatment planning system the SPC
analysis found that the a priori limits were no longer capable of indicating
control for 2 of the 3 metrics analyzed. The changes in the IMRT QA results were
clearly identified using SPC, indicating that it is a useful tool for finding
changes in the IMRT QA process. Routine application of SPC to IMRT QA results
would help to distinguish unintentional trends and changes from the random
variation in the IMRT QA results for individual plans.
PMID- 28516723
TI - Poster - Thur Eve - 40: Dynamic arc sliding window tests for checking MLC gap
consistency in rapid arc delivery.
AB - MLC gap control is critical for dosimetric accuracy in rotational IMRT (RapidArc,
VMAT) treatments. Systematic MLC gap change of 1 mm may cause 3-4% change of EUD
to PTV for a typical H&N RapidArc plan. Therefore it is important to monitor MLC
gap through QC procedures. For this purpose, we have created dynamic arc sliding
window (SW) plans with fixed width MLC slits sliding across a jaw defined field.
Plans with MLC slit widths of 5, 10, 15, and 20 mm, respectively, and the same
length of 20 cm (in Y direction) were created with 6MV photons in a single arc of
gantry angles from 182 degrees to 178 degrees . Dose delivered from these SW
plans was measured using an ion chamber in a cylindrical phantom placed at
isocentre, and values for dosimetric leaf gap (DLG) were derived based on
relative dose measurements. DLG measured in dynamic arc SW tests agrees with that
measured in fixed gantry angle SW fields to within 0.02 mm. We also extracted the
MLC leaf gaps during MLC travels in these dynamic arc SW deliveries from MLC
positions recorded in dynalog files, and compared to the MLC gaps in fixed gantry
SW fields. We found that MLC leaf gaps were maintained excellently constant
whether in dynamic arc or fixed gantry angle SW delivery, with typical standard
deviation of MLC gaps of only ~0.01mm for all involved leaf pairs. We believe
these dynamic arc SW tests are very useful for checking MLC leaf constancy for
RapidArc delivery.
PMID- 28516724
TI - Poster - Thur Eve - 51: Three-dimensional in-vivo EPID dosimetry of IMRT and VMAT
treatments.
AB - As radiation treatment delivery becomes more complex, including dynamic IMRT and
VMAT, the argument for routine patient dose verification becomes more compelling.
This work demonstrates a technique that utilizes our pre-existing portal dose
image prediction algorithm to compute 3D patient dose from recorded on-treatment
portal images. This approach can be applied on CT simulation data or daily cone
beam CT data sets. Here we demonstrate the robustness of our dose reconstruction
technique with phantom and patient examples, with delivery schemes including IMRT
and VMAT. For an example prostate treatment site, 3D dose distributions
reconstructed in the patient model are computed for each fraction, and DVHs
presented. Results indicate that the patient dose reconstruction algorithm
compares well with treatment planning system computed doses for controlled test
situations. For patient examples the 3D chi comparison values (similar to the
gamma comparison) ranged from 94.5% to 100% agreement for voxels > 10% maximum
dose for all treatments and phantom cases. We show an example where the DVH for
fraction nine of a prostate treatment fails acceptability criteria, due to a
previously unnoticed positioning error. Future work involves building our patient
dose reconstruction into a QA package, subsequently integrating it into a
clinical workflow. We are also investigating the use of this tool as a backbone
for an in-house adaptive radiotherapy implementation. This work is supported by
Varian Medical Systems.
PMID- 28516725
TI - The need for better preventative strategies for inflammatory bowel disease
patients at risk of herpes zoster virus.
AB - BACKGROUND: Immunosuppressed inflammatory bowel disease (IBD) patients have an
increased risk of herpes zoster virus (HZV) infection. The existing live
attenuated HZV vaccine is contraindicated in some of these patients and can only
be used with caution in others. AIMS: To describe characteristics of IBD patients
suffering HZV to enable implementation of risk mitigation strategies for those at
highest risk. METHODS: Gastroenterologists completed a proforma for IBD patients
who experienced HZV infection: IBD phenotype, details of HZV infection,
immunosuppression and any change to treatment upon diagnosis of HZV. RESULTS: A
total of 30 cases was identified: Crohn disease (CD) (n = 25) and ulcerative
colitis (n = 5). In total, 80% (20/25) of the CD patients had penetrating,
stricturing or perianal disease. Time from commencement of immunosuppression to
HZV infection was highly variable (range: 3 months to over 10 years). A total of
90% (27/30) of patients was on at least one immunosuppressive therapy; of those,
one-third was on monotherapy (9/27) and two-thirds (18/27) on dual therapy. A
total of 89% (24/27) of immunosupressed patients was on a thiopurine
(monotherapy; 6/27) or in combination (18/27). Complications of HZV occurred in
27% (8/30) of patients. CONCLUSION: Our series is consistent with existing
epidemiological analysis that identified more severe IBD and the use of multiple
immunosuppressive therapies as risk factors for HZV. If the promise of an
investigational subunit HZV vaccine is realised in immunocompromised patients,
better protection may be possible in the future. Thiopurine medications were the
most commonly used immunosuppressant in this series. Age and duration of
immunosuppressive therapy do not appear to predict HZV infection.
PMID- 28516726
TI - Clasper morphology of skates of the tribe Riorajini (Chondrichthyes: Rajiformes:
Arhynchobatidae) and its systematic significance.
AB - Claspers of adult specimens of the skate tribe Riorajini, family Arhynchobatidae,
comprising Atlantoraja and Rioraja, are described, compared, and systematically
reinterpreted based on material collected off southeastern and southern Brazil.
For the first time the external components and musculature of the clasper of
members of this tribe are described and related to internal (skeletal)
structures. The component pecten is present in all species of Atlantoraja but
absent in Rioraja. The new external component grip, an autapomorphy of A.
cyclophora fully developed in adults, is described. Rioraja presents dorsal
terminals 1 and 2, ventral marginal distally extended and ventral terminal
cartilages. Dorsal terminals 1 and 2, ventral marginal distally extended,
accessory terminals 2 and 3, and ventral terminal cartilages occur in
Atlantoraja. A new interpretation of the ventral marginal distally extended is
discussed. The dorsal terminal 1 of Atlantoraja has an inverted U shape but is
triangular in Rioraja. The accessory terminal 2 cartilage is reported for the
first time in Atlantoraja cyclophora. The accessory terminal 3 is present only in
A. platana and A. cyclophora, and absent in Rioraja and A. castelnaui. Many of
our findings concerning the clasper skeleton do not agree with previous
interpretations. The arrangement, distribution and systematic significance of
many of the terminal clasper components are discussed among rajoids.
PMID- 28516727
TI - Non-invasive longitudinal monitoring of angiogenesis in a murine full-thickness
cutaneous wound healing model using high-resolution three-dimensional ultrasound
imaging.
AB - BACKGROUND/PURPOSE: The aim of this study was to evaluate the longitudinal
monitoring of angiogenesis in a murine full-thickness cutaneous wound healing
model using high-resolution three-dimensional (3D) ultrasound imaging. METHODS:
Two C57BL/6 mice were used. Two-dimensional (2D) ultrasound images with the Color
Doppler mode were acquired at regular spatial intervals on day 9, 11, and 14
after wounding. 3D ultrasound images were processed by reconstructing the 2D
ultrasound image sequences. The wounds were harvested on day 14 and serial
sections were immunohistologically stained with an anti-CD31 antibody. RESULTS:
3D ultrasound imaging with the Color Doppler mode showed the distribution of
microvascular growth on days 9, 11, and 14 after wounding (44.6%, 51.5%, and
27.3% in wound 1, 55.8%, 38.1%, and 35.1% in wound 2, 60.6%, 62.6%, and 63.1% in
wound 3, and 15.8%, 42.0%, and 31.9% in wound 4, respectively). A correlation was
observed between % vascularity measured by paired 2D ultrasound imaging with the
Color Doppler mode and sections immunohistologically stained for the anti-CD31
antibody (r=0.927, 0.871, 0.717, and 0.913 for wounds 1, 2, 3, and 4,
respectively. P<.01). CONCLUSION: These results indicate that high-resolution 3D
ultrasound imaging is useful for longitudinally evaluating the distribution of
microvascular growth over the course of healing.
PMID- 28516728
TI - Increased heterogeneity of airway calibre in adult rats after hypoxia-induced
intrauterine growth restriction.
AB - BACKGROUND AND OBJECTIVE: Intrauterine growth restriction (IUGR) is associated
with asthma development. We hypothesized that IUGR disrupts airway development
leading to postnatal structural abnormalities of the airway that predispose to
disease. This study therefore examined structural changes to the airway and lung
in a rat model of maternal hypoxia-induced IUGR. METHODS: Pregnant rats were
housed under hypoxic conditions (11.5% O2 ) from gestational days (GDs) 13 to 20
(pseudoglandular-canalicular stages, i.e. period of airway development) and then
returned to normoxic conditions (21% O2 ). A control group of pregnant rats was
housed under normoxic conditions throughout pregnancy. Weights of male offspring
were recorded at birth and 7 weeks of age (adulthood), at which point lungs were
fixed for morphometry and stereology (n = 6/group), or bronchoalveolar lavage
fluid (BALF) was collected for cell counts (n = 6/group). RESULTS: IUGR offspring
were lighter at birth compared with control, but not at 7 weeks. While there was
no difference in mean airway dimensions or lung volume, there was greater
anatomical variation in airway lumen area in the IUGR group. A mathematical model
of the human lung was used to show that greater heterogeneity in lumen area in
IUGR-affected individuals increases bronchoconstriction during simulated
bronchial challenge. More macrophages were identified in the BALF of IUGR
offspring. CONCLUSION: The rat model demonstrates that IUGR leads to a more
heterogeneous distribution of airway lumen calibre in adulthood with potential
implications for bronchoconstriction in human subjects. Together with increased
lung macrophages, these findings support a phenotypic shift after IUGR that may
impact disease susceptibility.
PMID- 28516729
TI - Proteome analysis of Duck Tembusu virus (DTMUV)-infected BHK-21 cells.
AB - Duck Tembusu virus (DTMUV) is a newly emerging pathogenic flavivirus that has
caused huge economic losses to the duck industry in China since 2010. Moreover,
the infection has spread rapidly, posing a potential public health concern. In
this study, iTRAQ approach was first used to quantitatively identify
differentially expressed cellular proteins in DTMUV-infected BHK-21 cells which
are usually employed to produce veterinary vaccines for DTMUV, as well as other
flaviviruses by serial passage. We identified 192 differentially expressed
cellular proteins, including 11 upregulated and eight downregulated proteins at
24 h postinfection (hpi), as well as 25 upregulated and 151 downregulated
proteins at 48 hpi, of which TLR9, DDX3X, and DDX5 may play important roles in
virus propagation. Further, DDX3X could inhibit DTMUV replication by modulating
the IFN pathway via TBK1. In conclusion, our study is the first to analyze the
protein profile of DTMUV-infected cells by quantitative proteomics. We believe
that our findings provide valuable information in better understanding the host
response to DTMUV infection. These findings are particularly important in the
development of vaccine-based strategies.
PMID- 28516730
TI - Control of Pseudomonas mastitis on a large dairy farm by using slightly acidic
electrolyzed water.
AB - The disinfection effect of slightly acidic electrolyzed water (SAEW) use in a
farm where Pseudomonas mastitis has spread was evaluated. Despite the application
of antibiotic therapy and complete cessation of milking infected quarters,
numerous new and recurrent Pseudomonas aeruginosa clinical mastitis infections
(5.8-7.1% of clinical mastitis cases) occurred on the farm from 2003 to 2005.
Procedural changes and equipment modifications did not improve environmental
contamination or the incidence of Pseudomonas mastitis. To more thoroughly
decontaminate the milking parlor, an SAEW system was installed in 2006. All
milking equipment and the parlor environment were sterilized with SAEW (pH 5-6.5,
available chlorine 12 parts per million) before and during milking time. After
adopting the SAEW system, the incidence of clinical and subclinical Pseudomonas
mastitis cases decreased significantly (P < 0.0001) and disappeared. These
findings suggest that SAEW effectively reduced the incidence of mastitis in a
herd contaminated by Pseudomonas species. This is the first report to demonstrate
the effectiveness of disinfection by SAEW against mastitis pathogens in the
environment.
PMID- 28516731
TI - Alopecia areata - hyperactivity of the hypothalamic-pituitary-adrenal axis is a
myth?
AB - INTRODUCTION: Psychological stress is known to cause exacerbation of different
skin pathologies including alopecia areata (AA). A hyperactivity of the
hypothalamic-pituitary-adrenal axis (the HPA axis) in patients affected by AA (AA
patients) was proposed to be a neuroendocrine response to stress. Still little is
known about melanocyte-stimulating hormone (MSH) and cortisol production in AA
settings. AIM: The aim of the study was to compare trends in a production of MSH
and cortisol in patients with AA patients and healthy controls. MATERIAL AND
METHODS: Plasma concentrations of free cortisol and MSH were measured in 43 AA
patients (35.5 +/- 10.6 years) and 37 healthy subjects (35.9 +/- 10.5 years)
selected from the Dermatology Outpatient Clinic at Medical University of Silesia
in Katowice, Poland. Results were submitted to statistical analysis with Shapiro
Wilk W-test and subsequently nonparametric (Mann-Whitney U-test) or parametric
(Student's t-test) statistics were performed. RESULTS: Mean plasma level of MSH
was 5.39 ng/mL in AA patients and 5.71 ng/mL in healthy controls. The difference
between groups was non-significant (P = 0.435), but the control group manifested
higher values of MSH (Q75 = 13.6 ng/mL vs Q75 = 5.98 ng/mL) and this tendency was
especially stronger in females. AA patients had greater mean plasma level of
cortisol (157.63 +/- 91.16 ug/L) than healthy controls (123.32 +/- 71.28 ug/L);
however, the difference between them was also non-significant (P = 0.063). No sex
dependent tendency to a greater production of cortisol was found. CONCLUSIONS:
Expectations of disturbances in production of MSH and cortisol were not
fulfilled. Neither MSH nor cortisol plasma levels appear to be clearly changed in
AA patients.
PMID- 28516732
TI - Diadenosine tetraphosphate (Ap4A) - an E. coli alarmone or a damage metabolite?
AB - Under stress, metabolism is changing: specific up- or down-regulation of proteins
and metabolites occurs as well as side effects. Distinguishing specific stress
signaling metabolites (alarmones) from side products (damage metabolites) is not
trivial. One example is diadenosine tetraphosphate (Ap4A) - a side product of
aminoacyl-tRNA synthetases found in all domains of life. The earliest
observations suggested that Ap4A serves as an alarmone for heat stress in
Escherichia coli. However, despite 50 years of research, the signaling mechanisms
associated with Ap4A remain unknown. We defined a set of criteria for
distinguishing alarmones from damage metabolites to systematically classify Ap4A.
In a nutshell, no indications for a signaling cascade that is triggered by Ap4A
were found; rather, we found that Ap4A is efficiently removed in a constitutive,
nonregulated manner. Several fold perturbations in Ap4A concentrations have no
effect, yet accumulation at very high levels is toxic due to disturbance of zinc
homeostasis, and also because Ap4A's structural overlap with ATP can result in
spurious binding and inactivation of ATP-binding proteins. Overall, Ap4A met all
criteria for a damage metabolite. While we do not exclude any role in signaling,
our results indicate that the damage metabolite option should be considered as
the null hypothesis when examining Ap4A and other metabolites whose levels change
upon stress.
PMID- 28516733
TI - The interactive role of eating regulation and stress in the prediction of weight
related outcomes among college students.
AB - The interactive role of eating regulation and perceived stress on weight-related
outcomes was examined among 319 sophomore year college students (110 males and
209 females). Moderated regressions were used to examine interactions between
stress and eating regulation on study outcomes including body mass index (BMI)
and body fat. Eating regulation moderated associations between stress and BMI and
body fat outcomes. Students reporting high perceived stress, high autonomous
eating regulation, low controlled regulation, and low amotivation exhibited
higher outcomes (BMI and body fat) than those with similar eating regulation but
lower perceived stress. Students with lower autonomous eating regulation and
higher controlled regulation had no differences in study outcomes across levels
of stress. College students who regulate their eating behaviours for health
reasons (specifically showing autonomous regulation) exhibit higher BMI and body
fat when they report higher levels of perceived stress. Health promotion programs
for college students need to target education efforts towards stress reduction
and healthy eating behaviours.
PMID- 28516734
TI - Does co-occurring borderline personality disorder influence acute phase treatment
for first-episode psychosis?
AB - BACKGROUND: This aims of this study were: (1) to determine the prevalence of co
occurring borderline personality disorder (BPD) in a first-episode psychosis
(FEP) sample; (2) to determine differences between patients with and without BPD
on demographics, comorbidities and clinical risks and other variables; and (3) to
examine whether BPD comorbidity influenced treatment received by patients for FEP
during their first 3 months after service entry to a specialist early psychosis
service. METHODS: A file audit was conducted for 100 consecutive admissions to an
early psychosis service. Patients with a clinician-rated co-occurring diagnosis
of BPD were compared with patients without clinician-rated BPD on a range of
variables. RESULTS: Twenty-two percent of the FEP sample was diagnosed with co
occurring BPD by clinician ratings. The FEP group with co-occurring BPD was found
to be younger, more likely to have other comorbidities, and were at higher risk
of suicide and violent behaviour. Group differences were found in treatment
received for FEP, whereby patients with co-occurring BPD had poorer access to
standard treatment, including guideline concordant antipsychotic medication
prescription. CONCLUSION: Young people with co-occurring clinician-rated BPD and
FEP experienced greater difficulty accessing standard care for FEP and received
relatively different treatment, including different pharmacotherapy, compared
with those FEP patients without BPD. There is a need to develop new clinical
guidelines and effective treatments for this specific subgroup with early
psychosis and co-occurring BPD that take into account interpersonal and
"premorbid" aspects of their presenting problems.
PMID- 28516735
TI - Assessment of trophic ecomorphology in non-alligatoroid crocodylians and its
adaptive and taxonomic implications.
AB - Although the establishment of trophic ecomorphology in living crocodylians can
contribute to estimating feeding habits of extinct large aquatic reptiles,
assessment of ecomorphological traits other than the snout shape has scarcely
been conducted in crocodylians. Here, I tested the validity of the proposed
trophic ecomorphological traits in crocodylians by examining the correlation
between those traits and the snout shape (an established trophic ecomorphology),
using 10 non-alligatoroid crocodylian species with a wide range of snout shape. I
then compared the ontogenetic scaling of trophic ecomorphology to discuss its
adaptive and taxonomic significance. The results demonstrated that degree of
heterodonty, tooth spacing, size of supratemporal fenestra (STF), ventral
extension of pterygoid flange and length of lower jaw symphysis are significantly
correlated with snout shape by both non-phylogenetic and phylogenetic regression
analyses. Gavialis gangeticus falls outside of 95% prediction intervals for the
relationships of some traits and the snout shape, suggesting that piscivorous
specialization involves the deviation from the typical transformation axis of
skull characters. The comparative snout shape ontogeny revealed a universal trend
of snout widening through growth in the sampled crocodylians, implying the
existence of a shared size-dependent biomechanical constraint in non-alligatoroid
crocodylians. Growth patterns of other traits indicated that G. gangeticus shows
atypical trends for degree of heterodonty, size of STF, and symphysis length,
whereas the same trends are shared for tooth spacing and ventral extension of
pterygoid flange among non-alligatoroid crocodylians. These suggest that some
characters are ontogenetically labile in response to prey preference shifts
through growth, but other characters are in keeping with the conserved
biomechanics among non-alligatoroid crocodylians. Some important taxonomic
characters such as the occlusal pattern are likely correlated with ontogeny and
trophic ecomorphology rather than are constrained by phylogenetic relationships,
and careful reassessment of such characters might be necessary for better
reconstructing the morphological phylogeny of crocodylians.
PMID- 28516736
TI - Inorganic Colloidal Perovskite Quantum Dots for Robust Solar CO2 Reduction.
AB - Inorganic perovskite quantum dots as optoelectronic materials have attracted
enormous attention in light-harvesting and emitting devices. However,
photocatalytic conversion based on inorganic perovskite halides has not been
reported. Here, we have synthesized colloidal quantum dots (QDs, 3-12 nm) of
cesium lead halide perovskites (CsPbBr3 ) as a new type of photocatalytic
material. The band gap energies and photoluminescence (PL) spectra are tunable
over the visible spectral region according to quantum size effects on an atomic
scale. The increased carrier lifetime revealed by time-resolved PL spectra,
indicates the efficient electron-hole separation and transfer. As expected, the
CsPbBr3 QDs with high selectivity of greater than 99 % achieve an efficient yield
of 20.9 MUmol g-1 towards solar CO2 reduction. This work has opened a new avenue
for inorganic colloidal perovskite materials as efficient photocatalysts to
convert CO2 into valuable fuels.
PMID- 28516738
TI - Intrinsic fluorescence and mechanical testing of articular cartilage in human
patients with osteoarthritis.
AB - The degeneration of articular cartilage is the main cause of osteoarthritis (OA),
a common cause of disability among elderly patients. The aim of this study is to
understand the correlation between intrinsic fluorescence of articular cartilage
and its biomechanical properties in patients with osteoarthritis. Cylindrical
samples of articular cartilage 6 mm in diameter were extracted via biopsy punch
from the femoral condyles of 6 patients with advanced OA undergoing knee
replacement surgery. The mechanical stiffness and fluorescence of each cartilage
plug were measured by indentation test and spectrofluorometry. Maps of
fluorescence intensity, at excitation/emission wavelengths of 240-520/290-530 nm,
were used to identify wavelengths of interest. The mechanical stiffness and
fluorescence intensity were correlated using a Spearman analysis. The
excitation/emission maps demonstrated three fluorescence peaks at
excitation/emission wavelength pairs 330/390, 350/430 and 370/460 nm. The best
correlation between the fluorescence intensity and stiffness of cartilage was
obtained for the 330 nm excitation band [R=0.82, p=0.04]. The intrinsic
fluorescence of articular cartilage may have application in optically assessing
the state of cartilage in patients with osteoarthritis.
PMID- 28516737
TI - Iron status and inflammatory biomarkers in patients with acutely decompensated
heart failure: early in-hospital phase and 30-day follow-up.
PMID- 28516739
TI - Treatment of Propriospinal Myoclonus at Sleep Onset.
PMID- 28516740
TI - Toxic Leukoencephalopathy and Hypokalemia Due to Exposure to Trimethyltin.
PMID- 28516742
TI - A Mutation in the ACTA1 gene Manifesting Nemaline Myopathy with Central Nervous
System Lesions.
PMID- 28516741
TI - Letter to the Editor: Asymmetric and Upper-Body Parkinsonism in Patients with
Idiopathic Normal-Pressure Hydrocephalus.
PMID- 28516743
TI - A Novel APTX Variant and Ataxia with Oculomotor Apraxia Type 1.
PMID- 28516744
TI - Repetitive Nerve Stimulation in MuSK-Antibody-Positive Myasthenia Gravis.
AB - BACKGROUND AND PURPOSE: Responses to repetitive nerve stimulation (RNS) in
patients with muscle-specific tyrosine kinase (MuSK) antibody (Ab)-positive
myasthenia gravis (MG) vary depending on the muscles tested. We analyzed the RNS
responses of limb and facial muscles in MuSK-Ab-positive and acetylcholine
receptor (AChR)-Ab-negative MG (MuSK MG) and MuSK-Ab-negative and AChR-Ab
negative [double-seronegative (DSN)] MG patients. METHODS: We retrospectively
compared RNS responses between 45 MuSK MG and 29 DSN MG. RNS was applied to the
abductor digiti minimi, flexor carpi ulnaris, trapezius, orbicularis oculi, and
nasalis muscles. RESULTS: Abnormal RNS responses in limb muscles were observed in
22.2 and 58.6% of MuSK MG and DSN MG patients, respectively, with abnormal facial
responses observed in 77.8 and 65.5%, and abnormal responses observed in any of
the five muscles in 86.7 and 72.4%. Abnormal RNS responses in the abductor digiti
minimi or flexor carpi ulnaris were less frequent in MuSK MG (8.9 and 15.6%,
respectively) than in DSN MG (37.9 and 55.2%), whereas the findings for other
muscles were not significantly different between the groups. Abnormal facial
responses but normal limb responses were independently associated with MuSK MG
(odds ratio=5.224, 95% confidence interval=1.300-20.990). CONCLUSIONS: Abnormal
RNS responses primarily in facial muscles without involvement of limb muscles
were more pronounced in MuSK MG than in DSN MG. RNS of both facial and limb
muscles in AChR-Ab-negative MG can increase the test sensitivity and aid in early
suspicion of MuSK MG.
PMID- 28516745
TI - Gerstmann's Syndrome Associated with Right Parietal Hemorrhage and Arteriovenous
Malformation.
PMID- 28516746
TI - Vasculitis Findings for the Anterior Choroidal Artery in 3D-Time-of-Flight
Magnetic Resonance Angiography.
PMID- 28516747
TI - The History of Growth Hormone Treatment for GHD in Japan.
AB - In Japan, treatment of growth hormone deficiency with pituitary-extracted human
growth hormone (phGH) was covered by health insurance for the first time in 1975.
However, because of the shortage of phGH, the Foundation for Growth Science (FGS)
was founded in 1977 to control the use of the product by its registration system
and to collect pituitary glands in Japan. In 1986, recombinant human growth
hormone was first approved. Since then, the FGS has been involved in the
harmonization of growth hormone measurement, assessment for treatment eligibility
according to the diagnostic criteria by the research group of the Ministry of
Health and Welfare, and database generation and its utilization.
PMID- 28516748
TI - Standardization of Growth Hormone and Insulin-like Growth Factor-I Measurements.
AB - Measurement of the levels of growth hormone (GH) and its related factor insulin
like growth factor I (IGF-I) is essential for the diagnosis and treatment of GH
deficiency (GHD) and conditions related to excess GH such as acromegaly and
pituitary gigantism. Measurement of GH levels is also used as an indicator of
hypothalamic-pituitary function. Because of the marked variability in GH
measurements among kits, the Study Committee for GH and Its Related Factors of
The Foundation for Growth Science, Japan standardized GH values measured with
various commercially available GH assay kits in Japan. The committee also
established IGF-I reference values for Japanese subjects of all ages, from
childhood to adulthood. Hopefully, international harmonization of GH measurements
will be achieved in the future.
PMID- 28516750
TI - Quality of Life of SGA Children with Short Stature Receiving GH Treatment in
Japan.
AB - The objective of this study was to compare the quality of life (QOL) of small for
gestational age (SGA) children with short stature with that of children with
normal height, and examine the effects of growth hormone (GH) treatment on the
QOL of the SGA children using questionnaires administered to their parents or
guardians. The results showed that QOL in daily living of SGA children with short
stature was lower than that of normal children based on the perceptions of their
parents or guardians. In addition, GH treatment improved the physical domain of
QOL of SGA children with short stature. This study suggests that GH treatment can
improve QOL and reduce psychosocial problems related to short stature.
PMID- 28516749
TI - International Comparison of Adult Height in Children with Growth Hormone
Deficiency and Limitations of Growth Hormone Treatment in Japan.
AB - The approved therapeutic dose of growth hormone (GH) for growth hormone
deficiency (GHD) varies depending on the country. Japan has the lowest
therapeutic dose globally, with a single dose of 0.175 mg/kg/week. GH treatment
for GHD is considered as a replacement therapy and in fact, a dose of 0.175
mg/kg/week is slightly higher than GH secretion in prepubertal healthy children
but nearly the same as that of pubertal children. Although the same growth rate
as that of healthy children is expected in response to replacement therapy, the
catch-up growth observed for the first 1 to 2 years of GH treatment was
misinterpreted as an effect of the GH replacement therapy. The real effect of the
GH replacement therapy was the growth rate appeared after more than 3 years of GH
therapy, when patients showed nearly the same growth rate as healthy children.
Therefore, children with GHD can have a higher growth rate than healthy children
only for the first 1 to 2 years of GH therapy, after which their growth rate
begins to wane. In the United States and Europe, the various therapeutic doses
and high-dose treatment are accepted and the SD score of adult height after
treatment is higher than that in Japan. The improvement degree of the height SD
score and the adult height SD score with GH therapy are lower in Japan compared
with other countries that administer a similar therapeutic dose. This suggests
that the response to GH can be affected by race. Actual comparison of the
response to GH between Japanese and Caucasian patients using KIGS (Pharmacia
International Growth Database) data showed that both the short-term response and
the effect on adult height were reduced in Japanese patients. As there is a
strong positive correlation between adult height and height at the onset of
puberty, treatment methods that can increase pubertal growth will be considered
in the future for patients with GDH who enter puberty with short stature.
PMID- 28516751
TI - Growth Hormone Therapy and Brain Tumors.
AB - As one of the projects of the Adverse Events Study Group of the Foundation for
Growth Science in Japan, the literatures on the recurrence and / or regrowth or
new formation of brain tumors in patients treated with growth hormone (GH) were
reviewed. Since the tumor volume of the sellar lesion can be accurately evaluated
only by magnetic resonance imaging (MRI), the related literatures published after
1990 were retrieved by searching under keywords, such as GH, replacement therapy,
brain tumor, recurrence, tumor formation, etc. It is undeniable that GH therapy
may result in tumor enlargement only in a very small percentage of cases.
However, within a scientifically reliable range of confirmation with large-scale
researches and case-control studies, it can be considered that there is no
relation between GH therapy and the recurrence or new formation of brain tumors.
PMID- 28516752
TI - Growth Hormone Treatment and Adverse Events.
AB - We compiled the major adverse events included in the Annual Research Reports of
the Foundation for Growth Research published in and after 2000. We conducted a
review of approximately 32,000 patients treated with growth hormone (GH) who
subsequently developed leukemia and who were registered with the Foundation for
Growth Research (from 1975 to December 31 1997). We performed a literature review
and found that GH therapy was not associated with leukemia onset in patients with
no risk factors for leukemia. We also reported the onset of diabetes mellitus
(DM), scoliosis, and respiratory problems in patients with Prader-Willi syndrome
who were treated with GH. Osteoporosis, Hashimoto thyroiditis, and hyperlipemia
were relatively frequent complications of Turner syndrome (TS).
PMID- 28516753
TI - Revision of the Growth References for Japanese Girls with Turner Syndrome.
PMID- 28516754
TI - Adult Height in Patients with Turner Syndrome and Association with Lifestyle
related Diseases after Human Growth Hormone Treatment in Japan.
PMID- 28516755
TI - Iodine and Thyroid Function: A Historical Review of Goiter and the Current Iodine
Status in Japan.
PMID- 28516757
TI - Gastric Perforation Caused by an Intragastric Balloon: Endoscopic Findings.
AB - Intragastric balloon (IGB) insertion has been most frequently used in the West as
an effective endoscopic treatment for morbid obesity, in practice. Recently,
there is a growing number of cases requiring IGB deployment for obesity treatment
in Korea. One of the reported complications of IGB use is gastric perforation. A
47-year-old woman was admitted to the hospital with mild symptoms, 7 weeks after
having an IGB placed. Esophagogastroduodenoscopy was performed and gastric ulcer
perforation was observed in the ulcer base, where food particles were impacted.
Laparoscopic primary repair was done successfully. This was a case of gastric
perforation, secondary to poor compliance with a proton-pump inhibitor (PPI). PPI
and Helicobacter pylori eradication are important for ulcer prevention following
IGB deployment.
PMID- 28516756
TI - Carbon Dioxide versus Air Insufflation in Gastric Endoscopic Submucosal
Dissection: A Systematic Review and Meta-Analysis of Randomized Controlled
Trials.
AB - BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) with air insufflation is
commonly used for the staging and treatment of early gastric carcinoma. However,
carbon dioxide (CO2) use has been shown to cause less post-procedural pain and
fewer adverse events. The objective of this study was to compare the post
procedural pain and adverse events associated with CO2 and air insufflation in
ESD. METHODS: A systematic search was conducted for randomized control trials
(RCTs) comparing the two approaches in ESD. The Mantel-Haenszel method was used
to analyze the data. The mean difference (MD) and odds ratio (OR) were used for
continuous and categorical variables, respectively. RESULTS: Four RCTs with a
total of 391 patients who underwent ESD were included in our meta-analysis. The
difference in maximal post-procedural pain between the two groups was
statistically significant (MD, -7.41; 95% confidence interval [CI], -13.6 -
1.21; p=0.020). However, no significant differences were found in the length of
procedure, end-tidal CO2, rate of perforation, and postprocedural hemorrhage
between the two groups. The incidence of overall adverse events was significantly
lower in the CO2 group (OR, 0.51; CI, 0.32-0.84; p=0.007). CONCLUSIONS: CO2
insufflation in gastric ESD is associated with less post-operative pain and
discomfort, and a lower risk of overall adverse events compared with air
insufflation.
PMID- 28516759
TI - Reduced Graphene Oxide-Wrapped Nickel-Rich Cathode Materials for Lithium Ion
Batteries.
AB - The encapsulation of Ni-rich cathode materials (LiNi0.6Co0.2Mn0.2O2) for lithium
ion batteries in reduced graphene oxide (rGO) sheets is introduced to improve
electrochemical performances. Using (3-aminopropyl)triethoxysilane, the active
materials are completely wrapped with several rGO layers of ~2 nm thickness. By
virtue of the great electrical conductivity of graphene, the rGO-coated cathode
materials exhibit much enhanced electrochemical performances of cycling property
and rate capability. In addition, it is shown that the structural degradation of
the active materials, which is from the rhombohedral layered structure (R3m) to
the spinel (Fd3m) or rock-salt phase (Fm3m), is significantly reduced as well as
delayed due to the protection of the active materials in the rGO layers from
direct contact with electrolytes and the consequent suppression of side
reactions.
PMID- 28516760
TI - From Highly Fluorescent Donors to Strongly Absorbing Acceptors: The Tunable
Properties of Fluorubines.
AB - The synthesis and characterization of three novel fluorubine derivatives is
reported via three to four simple reaction steps with isolatable intermediates.
The functional dyes are characterized by their strong absorption peaks in the
visible region and their high fluorescence quantum yields. A significant and
useful feature is that the properties can be tuned over a wide range by changing
the pH. Transformation of the dyes into protonated amidinium salts leads to
narrower band gaps and to drastically lower LUMO energies. Further reduction of
the pH results in the doubly protonated species with a high electron-deficiency
and LUMO energies of -4.8 eV, bathochromic shifts, and a strong intensity
increase of up to epsilon = 120 000 M-1 cm-1.
PMID- 28516758
TI - Necrotizing Pancreatitis: Current Management and Therapies.
AB - Acute necrotizing pancreatitis accounts for 10% of acute pancreatitis (AP) cases
and is associated with a higher mortality and morbidity. Necrosis within the
first 4 weeks of disease onset is defined as an acute necrotic collection (ANC),
while walled off pancreatic necrosis (WOPN) develops after 4 weeks of disease
onset. An infected or symptomatic WOPN requires drainage. The management of
pancreatic necrosis has shifted away from open necrosectomy, as it is associated
with a high morbidity, to less invasive techniques. In this review, we summarize
the current management and therapies for acute necrotizing pancreatitis.
PMID- 28516761
TI - Facile and Sensitive Near-Infrared Fluorescence Probe for the Detection of
Endogenous Alkaline Phosphatase Activity In Vivo.
AB - Alkaline phosphatase (ALP) is an essential enzyme and widely distributes in a
variety of tissues. To date, various nanomaterial and small-molecule fluorescent
probes for ALP have been constructed successfully, but the emission wavelengths
of these probes are in the ultraviolet or visible range, which is not beneficial
for bioimaging. Herein, a hemicyanine-based near-infrared (NIR) fluorescent probe
named CyP is first synthesized and used to detect ALP activity. The
characteristics of probe CyP are as follows: (1) The probe possesses a facile
structure, which can be obtained by easy synthetic steps. (2) The fluorescence
emission of the sensing system is at 738 nm belonging to NIR region, which is
suitable for bioimaging in vivo. (3) The probe exhibits high sensitivity to ALP
with 10-fold fluorescence enhancement and low detection limit (0.003 U/mL) can
match the level of ALP in vivo. (4) The fluorescent change of the probe is
attributed to the fact that ALP-catalyzed cleavage of the phosphate group in CyP
induces the transformation of CyP (fluorescence off) into CyOH (fluorescence on),
which is proved by HPLC, 31P NMR, MS, and DFT calculation. (5) The NIR
fluorescent probe is applied for the detection of endogenous ALP activity in
various biological samples such as cell, tissue, and living animal with
satisfactory results.
PMID- 28516762
TI - Organophosphorus Flame Retardants in Pregnant Women and Their Transfer to
Chorionic Villi.
AB - The potential for prenatal exposure has recently raised concerns over the health
risks of endocrine disruptors; however, knowledge about human prenatal exposure
to organophosphorus flame retardants (OPFRs) is lacking. In this study, 2
ethylhexyl diphenyl phosphate (EHDPP), tributyl phosphate (TBP), triphenyl
phosphate (TPHP), and tris(2-chloroethyl) phosphate (TCEP) were detected in the
majority of chorionic villus samples, with median concentrations of 13.6, 18.8,
11.1, and 0.51 ng/g of dry weight (dw), respectively, significantly higher than
those in the matching maternal decidua samples (5.96, 10.8, 1.44, and 0.26 ng/g
of dw, respectively). The ratios of concentrations in chorionic villi (containing
embryos) to those in maternal deciduae (CMRs) were 4.17, 3.82, 2.81, and 2.00 for
EHDPP, TPHP, TBP, and TCEP, respectively, which correlated with their log Kow
values (p = 0.003). The results of transthyretin (TTR) binding assays indicated
that the stronger the binding ability to TTR, the higher the CMRs. The median
concentrations of the metabolites diphenyl phosphate (DPHP), dibutyl phosphate
(DBP), and bis(2-chloroethyl) phosphate (BCEP) were 4.11, 429, and 157 ng/g of dw
in chorionic villi, higher than those in deciduae (1.64, 181, and 25.4 ng/g of
dw, respectively). The ratios of DPHP/TPHP and DPHP/EHDPP were 0.20 and 0.43 in
chorionic villi and 1.24 and 2.03 in deciduae, respectively, much lower than
those of DBP/TBP and BCEP/TCEP (20.9 and 165.6 in chorionic villi and 13.1 and
35.3 in deciduae, respectively), suggesting that the difference in metabolism
between the deciduae and chorionic villi would affect their maternal transfer.
PMID- 28516763
TI - First Assessment of NOx Sources at a Regional Background Site in North China
Using Isotopic Analysis Linked with Modeling.
AB - Nitrogen oxides (NOx, including NO and NO2) play an important role in the
formation of atmospheric particles. Thus, NOx emission reduction is critical for
improving air quality, especially in severely air-polluted regions (e.g., North
China). In this study, the source of NOx was investigated by the isotopic
composition (delta15N) of particulate nitrate (p-NO3-) at Beihuangcheng Island
(BH), a regional background site in North China. It was found that the delta15N
NO3- (n = 120) values varied between -1.70/00 and +24.00/00 and the delta18O-NO3-
values ranged from 49.40/00 to 103.90/00. On the basis of the Bayesian mixing
model, 27.78 +/- 8.89%, 36.53 +/- 6.66%, 22.01 +/- 6.92%, and 13.68 +/- 3.16% of
annual NOx could be attributed to biomass burning, coal combustion, mobile
sources, and biogenic soil emissions, respectively. Seasonally, the four sources
were similar in spring and fall. Biogenic soil emissions were augmented in summer
in association with the hot and rainy weather. Coal combustion increased
significantly in winter with other sources showing an obvious decline. This study
confirmed that isotope-modeling by delta15N-NO3- is a promising tool for
partitioning NOx sources and provides guidance to policymakers with regard to
options for NOx reduction in North China.
PMID- 28516765
TI - Peptide Microarray-Based Metal Enhanced Fluorescence Assay for Multiple Profiling
of Matrix Metalloproteinases Activities.
AB - Matrix metalloproteinases (MMPs) are closely associated with cancer cell invasion
and metastasis. Herein, a fluorescence resonance energy transfer (FRET)-peptide
microarray-based metal enhanced fluorescence (MEF) assay is proposed for multiple
and sensitive profiling of MMPs activities on a novel Au/Ag@SiO2 substrate. The
Au/Ag@SiO2 substrate is prepared by electroless deposition of silver on gold
nanoparticle (GNP) seeds, followed by SiO2 shell coating and surface
functionalization. The specific FRET peptides are spotted on the Au/Ag@SiO2
substrate to sensitively detect MMPs (MMP-2, -3, -7, -9, -14) via fluorescence
recovery by the MMP cleavage of quenched peptide motifs and further enhanced by
MEF. Under the optimal conditions, the limits of detection are 12.2 fg mL-1 for
MMP-2, 60 pg mL-1 for MMP-3, 0.22 pg mL-1 for MMP-7, 102 fg mL-1 for MMP-9, and
0.68 ng mL-1 for MMP-14, respectively. The practicability of the FRET-peptide
microarray-based MEF assay is demonstrated by profiling of multiplexed MMPs
activities in various cell lines and clinical thyroid tissue samples of papillary
thyroid carcinoma (PTC) patients and thyroid nodules (TN) patients, and
satisfactory results are obtained.
PMID- 28516766
TI - In Situ Generated TEMPO Oxoammonium Salt Mediated Tandem Cyclization of beta
Oxoamides with Amine Hydrochlorides for the Synthesis of Pyrrolin-4-ones.
AB - A novel in situ generated TEMPO oxoammonium salt mediated one-pot tandem reaction
has been developed for the straightforward construction of pyrrolin-4-ones from
readily available beta-oxoamides with amine hydrochlorides. The reaction
tolerates various functional groups and represents a reliable method for the
synthesis of highly substituted pyrrolin-4-ones in good yields under mild
conditions. Detailed mechanistic studies disclosed that TEMPO oxoammonium salt
generated in situ was crucial for the transformation involving the formation of
enaminone precursors in situ by condensation of the beta-oxoamides with amines,
followed by sequential oxidative coupling with beta-oxoamides, intramolecular
cyclization, and 1,2-alkyl migration steps.
PMID- 28516764
TI - An Autoinhibitory Role for the Pleckstrin Homology Domain of Interleukin-2
Inducible Tyrosine Kinase and Its Interplay with Canonical Phospholipid
Recognition.
AB - Pleckstrin homology (PH) domains are well-known as phospholipid binding modules,
yet evidence that PH domain function extends beyond lipid recognition is
mounting. In this work, we characterize a protein binding function for the PH
domain of interleukin-2-inducible tyrosine kinase (ITK), an immune cell specific
signaling protein that belongs to the TEC family of nonreceptor tyrosine kinases.
Its N-terminal PH domain is a well-characterized lipid binding module that
localizes ITK to the membrane via phosphatidylinositol 3,4,5-trisphosphate (PIP3)
binding. Using a combination of nuclear magnetic resonance spectroscopy and
mutagenesis, we have mapped an autoregulatory protein interaction site on the ITK
PH domain that makes direct contact with the catalytic kinase domain of ITK,
inhibiting the phospho-transfer reaction. Moreover, we have elucidated an
important interplay between lipid binding by the ITK PH domain and the stability
of the autoinhibitory complex formed by full length ITK. The ITK activation loop
in the kinase domain becomes accessible to phosphorylation to the exogenous
kinase LCK upon binding of the ITK PH domain to PIP3. By clarifying the
allosteric role of the ITK PH domain in controlling ITK function, we have
expanded the functional repertoire of the PH domain generally and opened the door
to alternative strategies to target this specific kinase in the context of immune
cell signaling.
PMID- 28516767
TI - Synthesis and Structure of 3,3-Dimethylindoline Squaraine Rotaxanes.
AB - Squaraine rotaxanes are mechanically interlocked molecules comprised of a
dumbbell shaped squaraine dye inside a tetralactam macrocycle. Previous squaraine
rotaxanes have employed planar squaraine dyes with 4-aminophenyl, 2
aminothiophene, or N-amino units appended to the central C4O2 core. Here we
describe two rotaxanes that encapsulate a 3,3-dimethylindoline squaraine inside a
tetralactam with anthracene sidewalls. The rotaxanes were prepared by a templated
clipping reaction and an X-ray crystal structure shows that the squaraine gem
dimethyl groups force a relatively wide separation between the macrocycle
anthracene sidewalls. The decreased interaction between the encapsulated
squaraine and the anthracene sidewalls leads to a smaller red shift of the
squaraine absorption and emission bands. Solution-state studies show that the gem
dimethyl groups in 3,3-dimethylindoline squaraine dyes are large enough to
prevent macrocycle threading or rotaxane unthreading. One of the new rotaxanes
emits an orange light (560-650 nm), and there is a 10-fold enhancement in the
squaraine fluorescence quantum yield upon encapsulation as a rotaxane. This
orange-emitting dye completes the palette of known squaraine rotaxane
fluorophores whose emission profiles span the color range from green to near
infrared.
PMID- 28516768
TI - Trimetallic Nitride Endohedral Fullerenes Carboxyl-Gd3N@C80: A New Theranostic
Agent for Combating Oxidative Stress and Resolving Inflammation.
AB - Antioxidative and anti-inflammatory effects of trimetallic nitride endohedral
fullerenes carboxyl-Gd3N@C80, a newly developed magnetic resonance imaging (MRI)
contrast agent, were investigated. All hydrochalarone and carboxyl-functionalized
fullerenes showed effective radical (hydroxyl and superoxide anion) scavenging,
whereas the carboxyl-Gd3N@C80 more efficiently attenuated lipopolysaccharide
(LPS) induced oxidative stress in macrophages. Carboxyl-Gd3N@C80 also suppressed
LPS-elicited mRNA expression of pro-inflammatory inducible nitric oxide synthase
and tumor necrosis factor-alpha, and upregulated antioxidative enzyme axis Nrf2
and heme oxygenase-1, possibly via ERK but not AKT signaling pathways. Therefore,
carboxyl-Gd3N@C80 held a great promise in becoming a novel theranostic
nanoplatform for simultaneously deliver MRI contrast and therapeutic functions to
inflammation-related diseases.
PMID- 28516769
TI - Identification of Rotundone as a Potent Odor-Active Compound of Several Kinds of
Fruits.
AB - An investigation of the aromas of grapefruit, orange, apple, and mango revealed
the presence of an odor-active compound that gave off a strong woody odor when
assessed by gas chromatography-olfactometry. We isolated the compound from a high
boiling fraction of an orange essential oil, and subsequent nuclear magnetic
resonance analyses of the isolated compound identified it as rotundone. Mass
spectra and retention indices obtained from aroma concentrates of grapefruit,
apple, and mango were identical to those of rotundone, which was therefore
determined to be the common woody compound in these fruits. Sensory analyses were
performed to assess the effects of rotundone on model beverages of the various
fruits. It was revealed that rotundone added at even subthreshold levels to model
beverages did not confer directly the woody odor, but had significant effects on
the overall flavors of the beverages, helping them to better approximate the
natural flavors of the fruits.
PMID- 28516770
TI - Conjugated Polymers Act Synergistically with Antibiotics to Combat Bacterial Drug
Resistance.
AB - The emergence of drug-resistant bacteria severely challenges the antimicrobial
agents and antibacterial strategy. Here, we demonstrate a novel, simple, and
highly efficient combination therapy strategy by direct combinations of cationic
conjugated polymers (CCPs) with polypeptide antibiotics against Gram-negative and
Gram-positive bacteria based on a synergistic antibacterial effect. The
combination therapy method enhances the antibacterial efficacy with a
significantly reduced antibiotic dosage. Also, the highly efficient and
synergistic killing of drug-resistant bacteria is realized. Using combinations of
CCPs and antibiotics to show increased antibacterial activity, this strategy will
provide a much wider scope of the discovery of efficient antibacterial systems
than that of antibiotic-antibiotic combinations. The proposed combination therapy
method provides a universal and powerful platform for the treatment of pathogens,
in particular, the drug-resistant bacteria, and also opens a new way for the
development of efficient antibacterial systems.
PMID- 28516771
TI - Highly Selective Cerebral ATP Assay Based on Micrometer Scale Ion Current
Rectification at Polyimidazolium-Modified Micropipettes.
AB - Development of new principles and methods for cerebral ATP assay is highly
imperative not only for determining ATP dynamics in brain but also for
understanding physiological and pathological processes related to ATP. Herein, we
for the first time demonstrate that micrometer scale ion current rectification
(MICR) at a polyimidazolium brush-modified micropipette can be used as the signal
transduction output for the cerebral ATP assay with a high selectivity. The
rationale for ATP assay is essentially based on the competitive binding ability
between positively charged polyimidazolium and ATP toward negatively charged ATP
aptamer. The method is well responsive to ATP with a good linearity within a
concentration range from 5 nM to 100 nM, and high selectivity toward ATP. These
properties essentially enable the method to determine the cerebral ATP by
combining in vivo microdialysis. The basal dialysate level of ATP in rat brain
cortex is determined to be 11.32 +/- 2.36 nM (n = 3). This study demonstrates
that the MICR-based sensors could be potentially used for monitoring
neurochemicals in cerebral systems.
PMID- 28516772
TI - Synthesis of [2]Catenanes by Intramolecular Sonogashira-Type Reaction.
AB - The catalytic activity of macrocyclic phenanthroline-CuI complexes was utilized
to synthesize [2]catenanes by intramolecular Sonogashira-type reaction. The high
reactivity of the acyclic starting material was critical to synthesize the
[2]catenane in acceptable yields. The relationship between the yield of the
[2]catenane and the structure of the starting materials was disclosed.
PMID- 28516775
TI - Reagent Design and Ligand Evolution for the Development of a Mild Copper
Catalyzed Hydroxylation Reaction.
AB - Parallel synthesis and mass-directed purification of a modular ligand library,
high-throughput experimentation, and rational ligand evolution have led to a
novel copper catalyst for the synthesis of phenols with a traceless hydroxide
surrogate. The mild reaction conditions reported here enable the late-stage
synthesis of numerous complex, druglike phenols.
PMID- 28516774
TI - Multiplexed MRM-Based Protein Quantitation Using Two Different Stable Isotope
Labeled Peptide Isotopologues for Calibration.
AB - When quantifying endogenous plasma proteins for fundamental and biomedical
research - as well as for clinical applications - precise, reproducible, and
robust assays are required. Targeted detection of peptides in a bottom-up
strategy is the most common and precise mass spectrometry-based quantitation
approach when combined with the use of stable isotope-labeled peptides. However,
when measuring protein in plasma, the unknown endogenous levels prevent the
implementation of the best calibration strategies, since no blank matrix is
available. Consequently, several alternative calibration strategies are employed
by different laboratories. In this study, these methods were compared to a new
approach using two different stable isotope-labeled standard (SIS) peptide
isotopologues for each endogenous peptide to be quantified, enabling an external
calibration curve as well as the quality control samples to be prepared in pooled
human plasma without interference from endogenous peptides. This strategy
improves the analytical performance of the assay and enables the accuracy of the
assay to be monitored, which can also facilitate method development and
validation.
PMID- 28516776
TI - Electrochemical Generation of Individual O2 Nanobubbles via H2O2 Oxidation.
AB - Herein, we use Pt nanodisk electrodes (apparent radii from 4 to 80 nm) to
investigate the nucleation of individual O2 nanobubbles generated by
electrooxidation of hydrogen peroxide (H2O2). A single bubble reproducibly
nucleates when the dissolved O2 concentration reaches ~0.17 M at the Pt electrode
surface. This nucleation concentration is ~130 times higher than the equilibrium
saturation concentration of O2 and is independent of electrode size. Moreover, in
acidic H2O2 solutions (1 M HClO4), in addition to producing an O2 nanobubble
through H2O2 oxidation at positive potentials, individual H2 nanobubbles can also
be generated at negative potentials. Alternating generation of single O2 and H2
bubbles within the same experiment allows direct comparison of the critical
concentrations for nucleation of each nanobubble without knowing the precise
size/geometry of the electrode or the exact viscosity/temperature of the
solution.
PMID- 28516773
TI - Amphiphilic BODIPY-Hydroporphyrin Energy Transfer Arrays with Broadly Tunable
Absorption and Deep Red/Near-Infrared Emission in Aqueous Micelles.
AB - BODIPY-hydroporphyrin energy transfer arrays allow for development of a family of
fluorophores featuring a common excitation band at 500 nm, tunable excitation
band in the deep red/near-infrared window, and tunable emission. Their biomedical
applications are contingent upon retaining their optical properties in an aqueous
environment. Amphiphilic arrays containing PEG-substituted BODIPY and chlorins or
bacteriochlorins were prepared and their optical and fluorescence properties were
determined in organic solvents and aqueous surfactants. The first series of
arrays contains BODIPYs with PEG substituents attached to the boron, whereas in
the second series, PEG substituents are attached to the aryl at the meso
positions of BODIPY. For both series of arrays, excitation of BODIPY at 500 nm
results in efficient energy transfer to and bright emission of hydroporphyrin in
the deep-red (640-660 nm) or near-infrared (740-760 nm) spectral windows. In
aqueous solution of nonionic surfactants (Triton X-100 and Tween 20) arrays from
the second series exhibit significant quenching of fluorescence, whereas
properties of arrays from the first series are comparable to those observed in
polar organic solvents. Reported arrays possess large effective Stokes shift (115
260 nm), multiple excitation wavelengths, and narrow, tunable deep-red/near-IR
fluorescence in aqueous surfactants, and are promising candidates for a variety
of biomedical-related applications.
PMID- 28516777
TI - Improvements in Mass Spectrometry Assay Library Generation for Targeted
Proteomics.
AB - In data-independent acquisition mass spectrometry (DIA-MS), targeted extraction
of peptide signals in silico using mass spectrometry assay libraries is a
successful method for the identification and quantification of proteins. However,
it remains unclear if high quality assay libraries with more accurate peptide ion
coordinates can improve peptide target identification rates in DIA analysis. In
this study, we systematically improved and evaluated the common algorithmic steps
for assay library generation and demonstrate that increased assay quality results
in substantially higher identification rates of peptide targets from mouse organ
protein lysates measured by DIA-MS. The introduced changes are (1) a new spectrum
interpretation algorithm, (2) reapplication of segmented retention time
normalization, (3) a ppm fragment mass error matching threshold, (4) usage of
internal peptide fragments, and (5) a multilevel false discovery rate
calculation. Taken together, these changes yielded 14-36% more identified peptide
targets at 1% assay false discovery rate and are implemented in three new open
source tools, Fraggle, Tramler, and Franklin, available at
https://github.com/fickludd/eviltools . The improved algorithms provide ways to
better utilize discovery MS data, translating to substantially increased DIA
performance and ultimately better foundations for drawing biological conclusions
in DIA-based experiments.
PMID- 28516778
TI - Surfactant Assemblies on Selected Nanostructured Surfaces: Evidence, Driving
Forces, and Applications.
AB - Surfactant adsorption at solid-liquid interfaces is critical for a number of
applications of vast industrial interest and can also be used to seed surface
modification processes. Many of the surfaces of interest are nanostructured, as
they might present surface roughness at the molecular scale, chemical
heterogeneity, as well as a combination of both surface roughness and chemical
heterogeneity. These effects provide lateral confinement on the surfactant
aggregates. It is of interest to quantify how much surfactant adsorbs on such
nanostructured surfaces and how the surfactant aggregates vary as the degree of
lateral confinement changes. This review focuses on experimental evidence on
selected substrates, including gold- and carbon-based substrates, suggesting that
lateral confinement can have pronounced effects both on the amount adsorbed and
on the morphology of the aggregates as well as on a systematic study, via diverse
simulation approaches, on the effect of lateral confinement on the structure of
the surfactant aggregates. Atomistic and coarse-grained simulations conducted for
surfactants on graphene sheets and carbon nanotubes are reviewed, as well as
coarse-grained simulations for surfactant adsorption on nanostructured surfaces.
Finally, we suggest a few possible extensions of these studies that could
positively impact a few practical applications. In particular, the simultaneous
effect of lateral confinement and of the coadsorption of molecular compounds
within the surface aggregates is expected to yield interesting fundamental
results with long-lasting consequences in applications ranging from drug delivery
to the design of advanced materials.
PMID- 28516779
TI - Synthesis of Cubic-Shaped Pt Particles with (100) Preferential Orientation by a
Quick, One-Step and Clean Electrochemical Method.
AB - A new approach has been developed for in situ preparing cubic-shaped Pt particles
with (100) preferential orientation on the surface of the conductive support by
using a quick, one-step, and clean electrochemical method with periodic square
wave potential. The whole electrochemical deposition process is very quick (only
6 min is required to produce cubic Pt particles), without the use of particular
capping agents. The shape and the surface structure of deposited Pt particles can
be controlled by the lower and upper potential limits of the square-wave
potential. For a frequency of 5 Hz and an upper potential limit of 1.0 V (vs
saturated calomel electrode), as the lower potential limit decreases to the H
adsorption potential region, the Pt deposits are changed from nearly spherical
particles to cubic-shaped (100)-oriented Pt particles. High-resolution
transmission electron microscopy and selected-area electron diffraction reveal
that the formed cubic Pt particles are single-crystalline and enclosed by (100)
facets. Cubic Pt particles exhibit characteristic H adsorption/desorption peaks
corresponding to the (100) preferential orientation. Ge irreversible adsorption
indicates that the fraction of wide Pt(100) surface domains is 47.8%. The
electrocatalytic activities of different Pt particles are investigated by ammonia
electro-oxidation, which is particularly sensitive to the amount of Pt(100)
sites, especially larger (100) domains. The specific activity of cubic Pt
particles is 3.6 times as high as that of polycrystalline spherical Pt particles,
again confirming the (100) preferential orientation of Pt cubes. The formation of
cubic-shaped Pt particles is related with the preferential electrochemical
deposition and dissolution processes of Pt, which are coupled with the periodic
desorption and adsorption processes of O-containing species and H adatoms.
PMID- 28516780
TI - Dual-Colored Carbon Dot Ratiometric Fluorescent Test Paper Based on a Specific
Spectral Energy Transfer for Semiquantitative Assay of Copper Ions.
AB - Classical pH test papers are widely used to measure the acid-base degree of media
in a qualitative or semiquantitative manner. However, the extension of portable
and inexpensive methods to a wide range of analytes so as to eliminate the
tediousness of instrumental assays remains unsuccessful. Here, we report a novel
kind of dual-colored carbon dot (CD) ratiometric fluorescent test paper for the
semiquantitative assay of copper ions (Cu2+) by a dose-sensitive color evolution.
The preparation of the test paper is based on the following two interesting
findings: on the one hand, residual p-phenylenediamine at the surface of as
synthesized red CDs (r-CDs) efficiently binds Cu2+ ions to produce a strong
visible absorption that overlaps the emission of blue CDs (b-CDs); on the other
hand, the Cu2+ ions render the adsorption of small b-CDs onto the surface of
larger r-CDs through their dual-coordinating interactions with the surface
ligands of both r-CDs and b-CDs. These two mechanisms lead to a specific spectral
energy transfer to quench the fluorescence of b-CDs with a sensitive detection
limit of 8.82 nM Cu2+, whereas the red fluorescence of r-CDs is unaffected as a
stable internal standard. Ratiometric fluorescent test papers have been prepared
using a mixture of r-CDs and b-CDs (1:7) as ink by jetprinting on a piece of
paper. With the addition of Cu2+ ions, the blue test paper produces a consecutive
wide-colored evolution from blue to orange-red, with a dose-discerning ability as
low as 25 nM.
PMID- 28516781
TI - Patterns, Variability, and Predictors of Urinary Triclosan Concentrations during
Pregnancy and Childhood.
AB - Exposure to triclosan, an antimicrobial used in many consumer products, is
ubiquitous in the United States, yet only limited data are available on the
predictors and variability of exposure, particularly in children. We examined the
patterns, variability, and predictors of urinary triclosan concentrations in 389
mother-child pairs enrolled in the Health Outcomes and Measures of the
Environment Study from 2003 to 2006. We quantified triclosan in 3 urine samples
collected from women between 16 weeks of pregnancy and birth and 6 urine samples
collected from children between the ages of 1-8 years. For maternal and child
samples, we calculated intraclass correlation coefficients (ICCs) to assess
triclosan reproducibility and identified sociodemographic predictors of
triclosan. Among 8 year old children, we examined associations between triclosan
and personal-care product use. We detected triclosan in >70% of urine samples.
Median maternal triclosan varied across pregnancy from 17 to 11 ng/mL, while in
children, median concentrations increased from 3.6 to 17 ng/mL over the first 4
years of life, declining slightly at later ages. Triclosan reproducibility was
fair to good during pregnancy and for child samples taken weeks apart (ICCs = 0.4
0.6) but poor for annual child samples (ICCs = 0.2-0.4). Triclosan was 66% (95%
CI: 29-113) higher in 8 year olds using hand soap compared to nonusers and
increased monotonically with hand-washing frequency. Toothpaste use in children
was also positively associated with triclosan. Our results suggest that urinary
triclosan concentrations have modest stability over weeks to months; children are
exposed to triclosan through the use of some personal-care products.
PMID- 28516785
TI - Measurement of intact parathormone during operation for primary
hyperparathyroidism.
AB - In this prospective study, the role of the intact parathormone (iPHT) levels for
the verification of pathologic parathyroid tissue removal during
parathyroidectomy, was analyzed in 441 patients diagnosed with primary
hyperparathyroidism. The level of intact parathormone was obtained before the
initial incision (baseline level) and 10 minutes after the pathologic parathyroid
gland removal (control value). In 80 % of cases, the decrease of intact
parathormone was more than 50 % of the baseline level. The comparison of
preoperative and postoperative intact parathormone levels can also be used as
marker of parathyroid hyperplasia or persistent hyperparathyroidism. This method
is necessary mainly for performance of focused, miniinvasive approaches as well
as in reoperations. This method is of significant benefit in cases of negative
preoperative examination methods. The determination of intact parathormone level
increases the success of parathyroidectomy (Ref. 26).
PMID- 28516786
TI - Association of angiogenic cytokines (VEGF-A and VEGF-C) and clinical
characteristic in women with unexplained recurrent miscarriage.
AB - INTRODUCTION: Recurrent miscarriage (RM) defined as 2 or more spontaneous
miscarriage before 20 weeks of gestation, affects at least 1 % of couples trying
to conceive. In over 50 % of cases, the cause of the loss of pregnancy remains
unexplained. Reduced expression of Angiogenic factors such as: vascular
endothelial growth factor (VEGF-A) and VEGF-C has been linked with spontaneous
miscarriage, likely due to defective foetal and placental angiogenesis. AIMS AND
OBJECTIVES: To investigate the relationships between serum level of VEGF-A and
VEGF-C with clinical characteristic in women with URM and compare to pregnant and
healthy women. MATERIALS AND METHODS: A case-control study, which was conducted
between 90 non-pregnant women with history of RM, age-matched with 70 non
pregnant women without history of recurrent abortion with at least one child
(controls) and 70 pregnant women without history of recurrent abortion with at
least one child (controls). Those with unexplained RM were eligible. Demographic
and Anthropometric data were retrieved by pre-test questionnaire and serum level
of VEGF-A and VEGF-C measured by ELISA kit. RESULTS: This study showeds that
maternal levels of VEGF-A and VEGF-C were distinctly lower in RSA (189.87+/-88.1
vs 238.8+/-99.6) compared to healthy (239.1+/-99.7 vs 275.5+/-133.08) and
pregnant (301.5+/-76.4 vs 402.5+/-128.6) women as control groups. Univariate
analysis demonstrated that clinical characteristic factors were significantly
associated with concentration of VEGF-A and VEGF-C in cases and controls.
CONCLUSIONS: Our findings suggest that these molecules could be used as potential
predictive markers of miscarriage in these women presenting with URM (Tab. 4,
Fig. 5, Ref. 40).
PMID- 28516782
TI - Exploring Site-Specific N-Glycosylation of HEK293 and Plant-Produced Human IgA
Isotypes.
AB - The full potential of recombinant Immunoglobulin A as therapeutic antibody is not
fully explored, owing to the fact that structure-function relationships of these
extensively glycosylated proteins are not well understood. Here monomeric IgA1,
IgA2m(1), and IgA2m(2) variants of the anti-HER2 antibody (IgG1) trastuzumab were
expressed in glyco-engineered Nicotiana benthamiana plants and in human HEK293-6E
cells. All three IgA isotypes were purified and subjected to biophysical and
biochemical characterization. While no differences in assembly, antigen binding,
and glycosylation occupancy were observed, both systems vary tremendously in
terms of glycan structures and heterogeneity of glycosylation. Mass-spectrometric
analysis of site-specific glycosylation revealed that plant-produced IgAs carry
mainly complex-type biantennary N-glycans. HEK293-6E-produced IgAs, on the
contrary, showed very heterogeneous N-glycans with high levels of sialylation,
core-fucose, and the presence of branched structures. The site-specific analysis
revealed major differences between the individual N-glycosylation sites of each
IgA subtype. Moreover, the proline-rich hinge region from HEK293-6E cell-derived
IgA1 was occupied with mucin-type O-glycans, whereas IgA1 from N. benthamiana
displayed numerous plant-specific modifications. Interestingly, a shift in
unfolding of the CH2 domain of plant-produced IgA toward lower temperatures can
be observed with differential scanning calorimetry, suggesting that distinct
glycoforms affect the thermal stability of IgAs.
PMID- 28516783
TI - Antidiabetic Disruptors of the Glucokinase-Glucokinase Regulatory Protein Complex
Reorganize a Coulombic Interface.
AB - The glucokinase regulatory protein (GKRP) plays an essential role in glucose
homeostasis by acting as a competitive inhibitor of glucokinase (GCK) and
triggering its localization to the hepatocyte nucleus upon glucose deprivation.
Metabolites such as fructose 6-phosphate and sorbitol 6-phosphate promote
assembly of the GCK-GKRP complex, whereas fructose 1-phosphate and functionalized
piperazines with potent in vivo antidiabetic activity disrupt the complex. Here,
we establish the molecular basis by which these natural and synthetic ligands
modulate the GCK-GKRP interaction. We demonstrate that a small-molecule disruptor
of the protein-protein interaction utilizes a two-step conformational selection
mechanism to associate with a rare GKRP conformation constituting 3% of the total
population. Conformational heterogeneity of GKRP is localized to the N-terminus
and deleting this region eliminates the ability of sorbitol 6-phosphate to
promote the GCK-GKRP interaction. Stabilizing ligands favor an extended N
terminus, which sterically positions two arginine residues for optimal Coulombic
interaction with a pair of carboxylate side chains from GCK. Conversely,
disruptors promote a more compact N-terminus in which an interfacial arginine
residue is stabilized in an unproductive orientation through a cation-pi
interaction with tyrosine 75. Eliminating the ability to sample this binding
impaired conformation enhances the intrinsic inhibitory activity of GKRP.
Elucidating the molecular basis of ligand-mediated control over the GCK-GKRP
interaction is expected to impact the development and future refinement of
therapeutic agents for diabetes and cardiovascular disease, which result from
improper GKRP regulation of GCK.
PMID- 28516787
TI - Antiproliferative effect of a food coloring on colon cancer cell line.
AB - 4-MEI (4-Methylimidazole) is used as a chemical intermediate, crude material or
component in the manufacture of pharmaceuticals, photographic and
photothermographic chemicals, dyes and pigments and agricultural chemicals. 4-MEI
is unintentionally found in our food. Caramel colour (which is the most used
beverage colouring and food), dark beers and common brands of cola drinks may
comprise more than 100 MUg of this compound per 12-ounce serving. 4-MEI is widely
used by people and colon cancer is common in our countries. So, it was decided to
do in vitro analysis of anti-cancer effect of 4-MEI by MTT test using htc-116
cell line.In this study, mouse Htc-116 cell line was treated with 4-MEI
concentrations of 300, 450, 600 and 750 ug/mL for 24 hours and 48 hours periods,
after that antiproliferative effect of the 4-MEI was studied by MTT assay. In
this study 4-MEI at highest concentration of 24h and at all concentration for 48
h treatment time significantly inhibited cell proliferation when it was compared
to control. Also, exposing to the 4-MEI for 48 hours led to a decrease in cells
proliferation by concentration dependent manner. This result showed that 4-MEI
had anticancer effect in htc-116 cells. However, it has to be evaluated with
different new studies (Tab. 1, Fig. 4, Ref. 19).
PMID- 28516784
TI - In-Culture Cross-Linking of Bacterial Cells Reveals Large-Scale Dynamic Protein
Protein Interactions at the Peptide Level.
AB - Identification of dynamic protein-protein interactions at the peptide level on a
proteomic scale is a challenging approach that is still in its infancy. We have
developed a system to cross-link cells directly in culture with the special
lysine cross-linker bis(succinimidyl)-3-azidomethyl-glutarate (BAMG). We used the
Gram-positive model bacterium Bacillus subtilis as an exemplar system. Within 5
min extensive intracellular cross-linking was detected, while intracellular cross
linking in a Gram-negative species, Escherichia coli, was still undetectable
after 30 min, in agreement with the low permeability in this organism for
lipophilic compounds like BAMG. We were able to identify 82 unique interprotein
cross-linked peptides with <1% false discovery rate by mass spectrometry and
genome-wide database searching. Nearly 60% of the interprotein cross-links occur
in assemblies involved in transcription and translation. Several of these
interactions are new, and we identified a binding site between the delta and
beta' subunit of RNA polymerase close to the downstream DNA channel, providing a
clue into how delta might regulate promoter selectivity and promote RNA
polymerase recycling. Our methodology opens new avenues to investigate the
functional dynamic organization of complex protein assemblies involved in
bacterial growth. Data are available via ProteomeXchange with identifier
PXD006287.
PMID- 28516788
TI - Anti-oxidative effect of resveratrol on aluminum induced toxicity in rat cerebral
tissue.
AB - INTRODUCTION: The direct protective effects of resveratrol against oxidative
stress have been demonstrated in neuroglial cells, the mechanisms of these
effects are not fully understood. The aim of this research was to study the
effect of resveratrol on AL induced cerebral injury in rat. METHODS: We divided
the groups as follows with 10 animals each: a) Group I - served as control
receiving normal drinking water and diet ad libitum. b) Group II - animals were
administered aluminum at a dose level of 100 mg/kg body weight for a period of 6
weeks daily through oral gavage. c) Group III - animals were administered
aluminum at a dose level of 100 mg/kg body weight and resveratrol at a dose of 10
mg/kg body weight intraperitoneally for a period of 6 weeks daily. After 6 weeks
rats were anesthetized and decapitated. Brains were removed immediately and
frozen in liquid nitrogenRESULTS: The levels of SOD and GPx antioxidant enzymes
were decreased in all of the groups receiving aluminium, but it was less severe
in resveratrol treated group. SOD and GPx levels in aluminium + resveratrol group
were higher than in the aluminum group (p < 0.05). MDA level, as an index of
lipid peroxidation, increased significantly in all of the groups receiving
aluminium. MDA level was lower in aluminium + resveratrol group compared to
aluminum group and the difference was significant (p < 0.05). CONCLUSIONS: This
study suggests that resveratrol is effective in preventing AL induced toxicity by
reducing MDA production in cerebral tissue. Resveratrol also attenuated SOD and
GPx suppression in cerebral tissue significantly. Our findings provide the
rationale for further studies directed to understanding the mechanism of
resveratrol in preventing neurodeterioration (Tab. 1, Ref. 35).
PMID- 28516789
TI - Protective effect of pravastatin on doxorubicin-induced hepatotoxicity.
AB - OBJECTIVE: The present study was designed to investigate the possible protection
of pravastatin against hepatic oxidative stress and dysfunctions induced by
doxorubicin in rats. BACKGROUND: Statins have beneficial effects on oxidative
stress and inflammation. METHODS: Male Sprague-Dawley rats were divided into four
groups. Control group (received saline orally), Group 2 received pravastatin (20
mg/kg, i.p. for 15 days), Group 3 received single dose doxorubicin (15 mg/kg,
i.p.), Group 4 was treated with pravastatin (20 mg/kg, i.p.) daily from 5 days
before to 10 days after injection of doxorubicin (15 mg/kg, i.p.). Hepatic
toxicity was estimated by biochemical parameters and oxidative stress and
histopathological studies. RESULTS: Administration of doxorubicin indicated an
increase in ALT, AST, ALP, TG, cholesterol, LDL and total bilirubin levels (p <
0.01). Doxorubicin caused a reduction in HDL and albumin levels (p < 0.01) as
well as superoxide dismutase, glutathione peroxidase and catalase activities (p <
0.05) with a concomitant increase in liver malondialdehyde (p < 0.05) and liver
damage (p < 0.001). Pravastatin reduced the scale liver injury (p < 0.001) and
protected liver functions and other biochemical parameters (p < 0.01). Increase
in malondialdehyde level associated with a reduction in antioxidant activities in
the doxorubicin group was attenuated by pravastatin treatment (p < 0.05).
CONCLUSION: Results indicated that pravastatin has a protective effect on the
liver against doxorubicin-induced hepatotoxicity in rats (Tab. 3, Fig. 2, Ref.
34).
PMID- 28516790
TI - Oxidative effects of extremely low frequency magnetic field and radio frequency
radiation on testes tissues of diabetic and healthy rats.
AB - With the development of technology, people are increasingly under the exposure of
electromagnetic fields. Individuals with chronic diseases such as diabetes are
now long-term exposed to Radio Frequency-RF radiation and extremely low frequency
(ELF) magnetic fields (MFs). The purpose of this present study is to investigate
oxidative effects and antioxidant parameters of ELF MFs and RF radiation on
testis tissue in diabetic and healthy rats. Wistar male rats were divided into 10
groups. Intraperitoneal single dose STZ (65 mg/kg) dissolved in citrate buffer
(0.1M (pH 4.5)) was injected to diabetes groups. ELF MFs and RF radiation were
used as an electromagnetic exposure for 20 min/day, 5 days/week for one month.
Testis tissue oxidant malondialdehyde (MDA), and antioxidants glutathione (GSH),
and total nitric oxide (NOx) levels were determined. The results of ANOVA and
Mann-Whitney tests were compared; p < 0.05 was considered significant. ELF and RF
radiation resulted in an increase in testicular tissue MDA and NOX levels (p <
0.05), and caused a decrease in GSH levels (p < 0.05) in both healthy and
diabetic rats, yet more distinctively in diabetic rats. The most pronounced
effect was recorded in D-RF + ELF group (p < 0.005). Both radiation practices
increased the oxidative stress in testis tissue while causing a decrease in
antioxidant level which was more distinctive in diabetic rats (Tab. 1, Fig. 3,
Ref. 30).
PMID- 28516791
TI - Which one is more effective for the treatment of rat sepsis model: thalidomide or
etanercept?
AB - OBJECTIVE: We aimed to investigate the protective effect of selected treatment
agents on liver injury in lipopolysaccharide (LPS)-induced rat sepsis model.
BACKGROUND: The sepsis includes complex inflammatory responses between a
microbial pathogen and the host immune system, and leads to organ failure and
also death. METHODS: This study was performed with 29 male Wistar Albino rats.
Rats were divided randomly into five groups: Sham group, LPS-treated sepsis
group, LPS+thalidomide treated group, LPS+etanercept treated group and
LPS+thalidomide+etanercept treated group, respectively. Liver tissue tumor
necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta) and interleukin 6
(IL-6) levels were determined by enzyme-linked immuno-sorbent assay (ELISA)
method. The expression of nuclear factor kappa-light-chain-enhancer of activated
B cells (NF-kappaB) was performed using western blot analysis. RESULTS: The
levels of tissue TNF-alpha, IL-1beta and IL-6 were found statistically
significantly higher in sepsis group than in the sham group. TNF-alpha levels
were found statistically significantly decreased in LPS+etanercept and
LPS+thalidomide+etanercept treated groups when compared with LPS group (p <
0.05). For IL-1beta and IL-6 levels a statistically significant decline was
observed in the LPS+thalidomide and LPS+etanercept treated groups compared to the
LPS group (p < 0.05). Expression of NF-kappaB protein in liver tissue was
significantly elevated in the LPS group compared to sham group (p < 0.001). In
treatment groups, a marked decrease was observed in NF-kappaB protein expression.
CONLUSION: The results of this investigation suggested that etanercept and
thalidomide administration may have a beneficial effect on LPS-induced sepsis.
So, the present study may have significant clinical relevance, but clinical
trials are needed to confirm these results (Tab. 1, Fig. 1, Ref. 36).
PMID- 28516792
TI - Apoptosis of colon cancer cells under the effect of geldanamycin derivate.
AB - AIM: The apoptotic effect of geldanamycin derivative may be important for the
colorectal cancer therapy. The mechanisms of apoptosis require understanding of
the behavior of colon cancer cell line Colo-205 which mimics colon
adenocarcinoma. Therefore, the effect of IC50 dose of 17-allylamino-17
demethoxygeldanamycin (17-AAG) on the colon cancer cells in vitro was studied for
its anti-apoptotic activity. METHOD: Apoptotic ratio of the Colo-205 cells was
determined after 17-AAG application with terminal deoxynucleotidyl transferase
dUTP nick end labeling (TUNEL) staining and apoptosis related genes. Apoptosis
signal path related key mitochondrial proteins, cytochrome c, bcl-2, caspase 9
and Apaf-1 expression were examined with RT-PCR method. RESULTS: 17-AAG caused
induction of cell death. Apoptotic related genes such as cytochrome-c, Apaf-1 and
caspase-9 protein expressions were increased significantly (p < 0.05) and anti
apoptotic bcl-2 expression was decreased significantly (p < 0.05). Our results
indicated that the application of 17-AAG on Colo-205 cells showed anticancer
effect by the apoptosis due to alteration of apoptotic genes. CONCLUSION: The
apoptotic effect of 17-AAG as an natural product for alternative medicine would
be very important for the success and quality of life during the treatment of
colon carcinoma with the combination of anticancer drugs (Tab. 1, Fig. 2, Ref.
32).
PMID- 28516793
TI - Red or white wine consumption effect on atherosclerosis in healthy individuals
(In Vino Veritas study).
AB - AIMS: Consumption of wine has a protective effect on cardiovascular diseases.
Data from prospective, long-term, head-to-head comparisons of effects of
different drinks on markers of atherosclerosis have been insufficient. METHODS
AND RESULTS: In Vino Veritas (IVV) study is long-term, prospective, multi-centre,
randomized trial comparing effects of red and white wine on atherosclerosis. 157
healthy subjects were randomized to white or red wine consumption for one year.
We did not find increase in HDL-cholesterol in the whole group (1.66+/-0.58 vs
1.62+/-0.49, p=0.180) or difference between both groups (1.60+/-0.53 vs 1.64+/
0.46, p=0.634). At 12 months there was reduction of LDL-cholesterol in both
groups, but with no difference between the groups (3.37+/-0.75 vs 3.60+/-1.10,
p=0.134); there was no difference between the groups in total cholesterol, CRP,
fasting blood glucose and liver function tests. Both groups had comparable
differences from baseline in levels of parameters of oxidative stress.
CONCLUSION: We did not find any clinically relevant differences in the lipid
profile, CRP, fasting blood glucose and other markers of atherosclerosis, between
long-term consumption of red and white wine. Moreover, we were unable to confirm
the hypothesis that wine drinking is associated with an elevation of HDL (Tab. 7,
Fig. 1, Ref. 30).
PMID- 28516794
TI - Association of the postoperative white blood cells (WBC) count in peripheral
blood after radical surgical treatment of left upper lobe non-small cell lung
cancer (NSCLC) with overall survival - single center results.
AB - INTRODUCTION: The individual patient prognosis after radical surgery for Non
small cell lung cancer (NSCLC) of left upper lobe remains still unclear. The
purpose of this study is to evaluate the predictive value of elevated white blood
cell count in peripheral blood as early indicator of postoperative NSCLC
prognosis. METHODS: A retrospective statistical analysis was performed studying
patients subject to radical treatment of left upper lobe NSCLC in period of five
years with subsequent one to three-year monitoring of morbidity and mortality of
the patient population. The statistical ROC (Receiver Operating Characteristic)
analysis of the WBC count in peripheral blood third day after the operation was
used to evaluate the relationship with overall survival, with respect to patients
surviving for at least 24 months. RESULTS: Based on the results of the ROC
analysis with a total area under the curve (AUC) of 0.67, it is possible to
confirm that the WBC count established third day after the operation allows us to
classify patients into groups according to the 24-month overall survival.
CONCLUSION: Our findings confirm the potential of using WBC count to improve
current protocols to establish postoperative prognosis for NSCLC of the upper
left lobe (Tab. 2, Fig. 1, Ref. 11).
PMID- 28516795
TI - A comprehensive guide to telocytes and their great potential in cardiovascular
system.
AB - Telocytes, a recently discovered type of interstitial cells, have a very
distinctive morphology - the small cell body with long extensions, named
telopodes. In our review, apart from introducing general aspects of telocytes, we
focus on properties, functions and future potential of those cells in
cardiovascular system. However, physiological functions of telocytes in
cardiovascular system are still regarded as quite enigmatic. Previous studies
claim that they play a role in organogenesis and regeneration, bioelectrical
signalling, mechanoelectrical coupling, anti-oxidative protection, angiogenesis
and regulation of blood flow. As well, they are presumably connected with the
presence of blood-myocardium barrier and proper organisation of extracellular
matrix. Moreover, there exists a significant link between the quantity of
telocytes in tissue and numerous cardiovascular diseases such as: myocardial
infarction, cardiomyopathies, systemic sclerosis, heart failure, atrial
fibrillation, isolated atrial amyloidosis, myxomatous valve degeneration and
hyperplastic consequences of vascular injury. Thanks to their unique properties,
telocytes might be a breakthrough in treatment of cardiovascular diseases, as
they may be effective in reversing effects of myocardial infarction. Telocytes
also may play a major role in tissue engineering - they might be the key factor
in creating stable and efficient vascular network in larger synthetic tissues or
organs (Tab. 1, Fig. 3, Ref. 53).
PMID- 28516796
TI - Legionella spp. in dental unit waterlines.
AB - OBJECTIVE: To determine the current presence of Legionella spp. in the output
water of dental unit waterlines (DUWLs) and examine its mitigation by
disinfection at the Institute of Dentistry and Oral Sciences, Faculty of Medicine
and Dentistry, Palacky University Olomouc and University Hospital Olomouc.
MATERIAL AND METHODS: The first stage of our survey involved collecting samples
of DUWL output water from 50 dental chair units (DCUs), and 2 samples of the
incoming potable water. In October 2015, a one-time disinfection (1 % Stabimed)
of DUWLs was conducted. This was followed by collecting 10 control samples
(survey stage 2). RESULTS: From the total of 50 samples (survey stage 1), 18
samples (36.0 %) tested positive for Legionella spp. Following the disinfection,
nine of the ten samples no longer showed any presence of Legionella. CONCLUSION:
Based on culture results, the one-time disinfection (1 % Stabimed) was effective.
We are unable to comment on the duration of positive effect of disinfection on
the occurrence of Legionella spp. in the outlet water. It was a one-time survey
(Tab. 2, Ref. 32).
PMID- 28516798
TI - Complementary and Alternative Medicine Use in Uninsured Children in Texas.
AB - Use of complementary and alternative medicine (CAM) among US children is 12%
according to the 2012 National Health Interview Study. Certain pediatric
populations have higher CAM use. We studied an uninsured population because
limited access to care likely results in higher CAM use. We surveyed 250
uninsured patients in a free pediatric mobile clinic program. In the largely
Hispanic population, rate of CAM use in the preceding 12 months was 45% among
children and 59% among parents. Ninety-one percent of children who used CAM had
parents who used CAM while only 32% of parents used CAM for themselves but did
not use CAM for their children ( P < .001). Seven parents (3%) and 4 children
(2%) had ever discussed their CAM use with a physician. Since CAM use is
significant in this uninsured population and families do not generally discuss
CAM with physicians, health care providers must ask about CAM use and provide
guidance.
PMID- 28516797
TI - Blood glucose and insulin and correlation of SLC25A13 mutations with biochemical
changes in NICCD patients.
AB - Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a
hereditary metabolic disease arising from biallelic mutations of SLC25A13. This
study aimed to explore the characteristics of fasting blood glucose (FBG),
fasting insulin (FINS) and C-peptide (C-P) levels in NICCD infants, analyze their
SLC25A13 genetic mutations and further discuss the correlation between SLC25A13
genetic mutations and biochemical changes. Seventy-two cases of infants with
cholestasis disease were gathered. Among them, 36 cases with NICCD diagnosis were
case group. Meanwhile, 36 cases with unknown etiology but excluded NICCD were
control group. FBG, FINS, C-P, ALT, AST, GGT, ALP, TG, HDL-C, LDL-C and Non-HDL-C
were collected from all subjects, and DNA was extracted from venous blood for
SLC25A13 mutations detection. The incidence of hypoglycemia was 3% in NICCD
group. There were no significant statistical difference of FBG, FINS and C-P
between NICCD and INC groups ( P > 0.05). ALT, LDL-C and Non-HDL-C levels in
NICCD group were lower than the INC group, while SLC25A13 mutations were
associated with the level of GGT ( P < 0.05). Ten different SLC25A13 genetic
mutations were detected, among which, 851del4, IVS16ins3kb, IVS6+5 G > A and
1638ins23 mutations made up 82% of all mutations. The incidence of hypoglycemia
may be higher in small gestational age infants with NICCD. Low LDL-C may be one
of the characteristics of dyslipidemia in NICCD infants. There was a correlation
between SLC25A13 gene mutations distribution and the GGT level, but the meaning
of this finding remains to be further in-depth study. Impact statement This study
aims to compare FBG, FINS, C-P, other biochemical and clinical manifestations
between NICCD and non-NICCD infants, and discuss differential diagnosis of NICCD
and INC beyond the genetic analysis. And investigate the correlation between
SLC25A13 genetic mutations and biochemical changes. This work presented that
incidence of hypoglycemia may be higher in small gestational age infants with
NICCD. Low LDL-C may be one of the characteristics of dyslipidemia in NICCD
infants. There was a correlation between SLC25A13 gene mutations distribution and
the GGT level.
PMID- 28516800
TI - Undertriage of Pediatric Major Trauma Patients in the United States.
AB - Although trauma undertriage has been widely discussed in the literature,
undertriage in the pediatric trauma population remains understudied. Using the
2009-2013 Nationwide Emergency Department Sample, we assessed the national
undertriage rate in pediatric major trauma patients (age <=16 years and injury
severity score [ISS] >15), and identified factors associated with pediatric
trauma undertriage. Nationally, 21.7% of pediatric major trauma patients were
undertriaged. Children living in rural areas were more likely to be undertriaged
( P = .02), as were those without insurance ( P = .00). Children with life
threatening injuries were less likely to be undertriaged ( P < .0001), as were
those with chronic conditions ( P < .0001). Improving access to specialized
pediatric trauma care through innovative service delivery models may reduce
undertriage and improve outcomes for pediatric major trauma patients.
PMID- 28516801
TI - Representations of mental health and arts participation in the national and local
British press, 2007-2015.
AB - We analysed news articles published in national and local British newspapers
between 2007 and 2015 to understand (1) how mental health and arts participation
were framed and (2) how the relationships between participants in arts
initiatives were conceptualised. Using corpus-assisted qualitative frame
analysis, we identified frames of recovery, stigma and economy. The recovery
frame, which emphasised that mental illness can be treated similarly to physical
illness, positioned arts participation as a form of therapy that can complement
or substitute medication. The stigma frame presented arts participation as a
mechanism for challenging social conceptions that mentally ill individuals are
incapable of productive work. The economy frame discussed the economic burden of
mentally ill individuals and portrayed arts participation as facilitating their
return to employment. Using thematic analysis, which paid attention to the
representation of social actors, we found that service users were identified as
the prime beneficiaries of arts initiatives, and arts participation was
conceptualised as a way to bring people with mental health issues together. We
discuss these findings against existing research on media representations of
mental health and the concept of 'mutual recovery' and suggest what wider
concurrent developments in the areas of mental health and the media may account
for the uncovered frames and themes.
PMID- 28516799
TI - Oral Health Promotion During Well Visits.
AB - Training pediatric residents in Bright Futures and oral health concepts is
critical to improving oral health. This study's objective was to determine the
skill level of pediatric residents in integrating oral health promotion during
health supervision visits of 12- to 35-month-old children. One hundred forty
three pediatric residents participated in an evaluation of the effectiveness of a
Bright Futures oral health curriculum. Competencies assessed preintervention
included partnership building, communication, and integration of oral health
concepts. Pediatric residents' abilities to integrate oral health promotion into
health supervision visits varied considerably. Residents demonstrated greater
skill in communication and partnership building compared with oral health
promotion behaviors and performance of an oral examination. Further education is
needed at a national level if we are to meet Healthy People 2020 goals.
PMID- 28516802
TI - The Influence of Heating on Toe pressure in Patients with Peripheral Arterial
Disease.
AB - BACKGROUND AND AIM: The toe skin temperature in vascular patients can be low,
making reliable toe pressure measurements difficult to obtain. The aim of this
study was to evaluate the effect of heating on the toe pressure measurements.
MATERIALS AND METHODS: A total of 86 legs were examined. Brachial pressure and
toe pressure were measured at rest in a supine position using a laser Doppler
device that also measured skin temperature. After heating the toes for 5 min with
a heating pad, we re-measured the toe pressure. Furthermore, after heating the
skin to 40 degrees with the probe, toe pressures were measured a third time.
RESULTS: The mean toe skin temperature at the baseline measurement was 24.0
degrees C (standard deviation: 2.8). After heating the toes for 5 min with a warm
heating pad, the skin temperature rose to a mean 27.8 degrees C (standard
deviation: 2.8; p = 0.000). The mean toe pressure rose from 58.5 (standard
deviation: 32) to 62 (standard deviation: 32) mmHg (p = 0.029). Furthermore,
after the skin was heated up to 40 degrees C with the probe, the mean toe
pressure in the third measurement was 71 (standard deviation: 34) mmHg (p =
0.000). The response to the heating varied greatly between the patients after the
first heating-from -34 mmHg (toe pressure decreased from 74 to 40 mmHg) to +91
mmHg. When the toes were heated to 40 degrees C, the change in to toe pressure
from the baseline varied between -28 and +103 mmHg. CONCLUSION: Our data indicate
that there is a different response to the heating in different clinical
situations and in patients with a different comorbidity.
PMID- 28516803
TI - Differentials in Cardiovascular Risk Factors and Diabetes by Socioeconomic Status
and Sex in Kalutara, Sri Lanka.
AB - Since 1950, cardiovascular disease (CVD) has emerged as a leading cause of
mortality in Sri Lanka, especially in men. In 2014, a survey in Kalutara to
assess CVD and type 2 diabetes mellitus (T2DM) risk factors in adults aged 25 to
64 years (n = 1011), and associations with sex and socioeconomic status (SES),
found similar CVD risk factors in both sexes, except for daily tobacco smoking at
19% in men and nil in women, and higher body mass index (BMI) in women than men.
With increasing SES in men, there were significant linear increases in mean BMI,
waist circumference, mean systolic and diastolic blood pressure, mean fasting
plasma glucose, and T2DM prevalence, but decreases in tobacco smoking. Whereas in
women higher SES was associated with a significant increase in mean BMI, but a
significant decrease in hypertension prevalence. Tobacco smoking is the main risk
factor explaining higher CVD mortality in men compared with women.
PMID- 28516804
TI - Spinal cord atrophy as a primary outcome measure in phase II trials of
progressive multiple sclerosis.
AB - OBJECTIVES: To measure the development of spinal cord (SC) atrophy over 1 year in
patients with progressive multiple sclerosis (PMS) and determine the sample sizes
required to demonstrate a reduction in spinal cord cross-sectional area (SC-CSA)
as an outcome measure in clinical trials. METHODS: In total, 44 PMS patients (26
primary progressive multiple sclerosis (PPMS), 18 secondary progressive multiple
sclerosis (SPMS)) and 29 healthy controls (HCs) were studied at baseline and 12
months. SC-CSA was measured using the three-dimensional (3D) fast field echo
sequences acquired at 3T and the active surface model. Multiple linear
regressions were used to investigate changes in imaging measurements. RESULTS:
PPMS patients had shorter disease duration, lower Expanded Disability Status
Scale (EDSS) and larger SC-CSA than SPMS patients. All patients together showed a
significantly greater decrease in percentage SC-CSA change than HCs, which was
driven by the PPMS. All patients deteriorated over 1 year, but no association was
found between percentage SC-CSA change and clinical changes. The sample size per
arm required to detect a 50% treatment effect over 1 year, at 80% power, was 57
for PPMS and 546 for SPMS. CONCLUSION: SC-CSA may become an outcome measure in
trials of PPMS patients, when they are at an early stage of the disease, have
moderate disability and modest SC atrophy.
PMID- 28516805
TI - Mesial temporal lobe and subcortical grey matter volumes differentially predict
memory across stages of multiple sclerosis.
AB - BACKGROUND/OBJECTIVE: Memory deficits due to multiple sclerosis (MS) have been
variably linked to lower subcortical grey matter (SCGM) and mesial temporal lobe
(MTL) volumes. We investigated which is the better predictor and whether this
changes across disease stages. METHODS/RESULTS: Memory was assessed in 315
patients. Magnetic resonance imaging (MRI) measured volumes of total brain, grey
matter, white matter, MTL (hippocampus, amygdala) and SCGM (thalamus, caudate).
MTL predicted memory in the total sample and in patients with earlier (<10 years)
or later (?10 years) relapsing disease. SCGM (specifically thalamus) predicted
memory in progressive patients. CONCLUSIONS: Neuroanatomical correlates of memory
deficits differ across disease stages.
PMID- 28516806
TI - Is bisphenol A exposure associated with the development of glucose intolerance
and increased insulin resistance in Thais?
AB - Bisphenol A (BPA), the monomeric component of polycarbonate plastics, reportedly
possesses endocrine-disrupting effects. Exposure to low levels of BPA during more
vulnerable periods leads to abnormalities related to sexual development in
experimental animals. Moreover, recently a few epidemiological studies in
Caucasians have demonstrated the association of BPA exposure with type 2
diabetes. Therefore, in the present study we examined the association of BPA
exposure and abnormal glucose tolerance in Thais. This is a cross-sectional study
of 240 participants aged at least 50 years, randomly selected by computer
generated random numbers within each glucose tolerance status from an oral
glucose tolerance study of 661 participants. There were 80 participants in each
group of type 2 diabetes, impaired glucose tolerance (IGT) and normal glucose
tolerance (NGT). Serum BPA was measured by competitive ELISA. The detection rate
of BPA was significantly higher in participants with IGT compared to those with
NGT ( p < 0.05), while no difference was found between participants with type 2
diabetes and NGT. When participants with type 2 diabetes were stratified into
those with fasting plasma glucose (FPG) under the diabetic threshold (<126 mg/dL)
and those over (>=126 mg/dL), it was found that those with FPG under the diabetic
threshold had measurable rates of BPA comparable to those with IGT, and rates
significantly higher than the NGT group ( p < 0.05), while those with FPG over
the diabetic threshold did not have higher rates of measurable BPA compared with
the NGT group. In conclusion, BPA exposure is not uncommon in Thais. There is an
association between BPA exposure and IGT, but not type 2 diabetes.
PMID- 28516807
TI - Neurofeedback-Based Enhancement of Single Trial Auditory Evoked Potentials:
Feasibility in Healthy Subjects.
AB - Previous studies showed a global reduction of the event-related potential
component N100 in patients with schizophrenia, a phenomenon that is even more
pronounced during auditory verbal hallucinations. This reduction assumingly
results from dysfunctional activation of the primary auditory cortex by inner
speech, which reduces its responsiveness to external stimuli. With this study, we
tested the feasibility of enhancing the responsiveness of the primary auditory
cortex to external stimuli with an upregulation of the event-related potential
component N100 in healthy control subjects. A total of 15 healthy subjects
performed 8 double-sessions of EEG-neurofeedback training over 2 weeks. The
results of the used linear mixed effect model showed a significant active
learning effect within sessions ( t = 5.99, P < .001) against an unspecific
habituation effect that lowered the N100 amplitude over time. Across sessions, a
significant increase in the passive condition ( t = 2.42, P = .03), named as
carry-over effect, was observed. Given that the carry-over effect is one of the
ultimate aims of neurofeedback, it seems reasonable to apply this neurofeedback
training protocol to influence the N100 amplitude in patients with schizophrenia.
This intervention could provide an alternative treatment option for auditory
verbal hallucinations in these patients.
PMID- 28516808
TI - Implication of foam sclerosant inactivation by human whole blood in a laboratory
setting.
AB - Background During sclerotherapy, it has been recommended to confirm intravenous
placement of the needle by aspirating blood into the sclerosant syringe. This may
inactivate some, or all of the sclerosant. Aims To quantify the volume of human
blood needed to completely inactivate 1 ml of sodium tetradecyl sulphate, and
comparing fresh blood and blood that has been stored in an
ethylenediaminetetraacetic acid tube. Methods A series of manual titrations were
carried out following a procedure developed at STD Pharmaceutical Products Ltd
(Hereford, UK) and listed in the British Pharmacopeia. Three percent of sodium
tetradecyl sulphate stock solutions were made with increasing volumes of blood
and titrated against benzethonium chloride to determine the active concentration
(% w/v) of sodium tetradecyl sulphate remaining in the solution. Results A
calculated approximation showed 0.3 ml of blood is required to fully inactivate 1
ml of 3% sodium tetradecyl sulphate when made into a foam. A comparison was made
between the use of fresh blood and blood stored in ethylenediaminetetraacetic
acid tubes. Blood stored in ethylenediaminetetraacetic acid tubes showed more
inactivation of sodium tetradecyl sulphate, but this was not significant at the P
<= 0.05 level. Conclusion The data from our study have shown that a minimum of
0.3 ml of fresh blood is required to inactivate 1 ml of 3% sodium tetradecyl
sulphate as a foam and it is not significantly affected by storing blood in an
ethylenediaminetetraacetic acid tube. Our methodology suggests that during foam
sclerotherapy treatment, blood should not be aspirated into the syringe to
confirm position, and that ultrasound guidance is more appropriate for needle
placement.
PMID- 28516809
TI - Real-time MRI-guided percutaneous sclerotherapy treatment of venous low-flow
malformations in the head and neck.
AB - Purpose This manuscript describes the technique of real-time MRI-guided
sclerotherapy for low-flow venous malformations in the head and neck based on our
institutional experience. Materials and methods Ethanolamine oleate is used as
the sclerosant and is mixed with gadolinium for visualization during the
procedure. The five procedural steps include: (I) an initial tri-plane T2
weighted sequence to visualize the lesion; (II) a T1 FSE or trueFISP sequence to
assess needle placement and advancement within the lesion; (III) a tri-plane T1
FLASH sequence to monitor sclerosant injection; (IV) a T1 FSE or VIBE sequence to
assess sclerosant coverage of the malformation before needle removal; (V) a post
procedural tri-plane T1 fat-saturated sequence to confirm sclerosant coverage of
the lesion. Periprocedural medications typically include steroids, antibiotic
prophylaxis, and non-steroidal anti-inflammatory medication. Patients are
typically admitted for overnight observation. Conclusion Real-time MRI-guided
sclerotherapy for low-flow venous malformations in the head and neck is effective
and safe.
PMID- 28516811
TI - European Board of Hand Surgery Diploma Examination 2016 (20-21 June, 2016,
Santander, Spain).
PMID- 28516810
TI - The role of meaning in life: mediating the effects of perceived knowledge of
stroke on depression and life satisfaction among stroke survivors.
AB - OBJECTIVE: Meaning-making is a way of coping when facing adverse events. A
paucity of literature suggests other possible factors (e.g. delivery of
knowledge) can influence how chronic illness survivors (i.e. stroke survivors in
rehabilitation) cope with illness. This article explores the importance and
significance of meaning in life as a mediator between perceived stroke knowledge
and psychological wellbeing among stroke survivors and how such processes can be
applied in practice to promote their psychological wellbeing. METHODS: A sample
of N = 192 elderly aged 60 or above who experienced a recent stroke completed a
survey to assess their levels of cognitive ability, physical function, perceived
knowledge of stroke, meaning in life, life satisfaction, and depression.
Correlation and mediation analyses using the Sobel test were conducted to clarify
the role of meaning in life among stroke survivors. RESULTS: Both perceived
knowledge of stroke ( r = 0.35, P < 0.001) and meaning in life had positive
correlations with life satisfaction ( r = 0.37, P < 0.001) and a negative
correlation with depression. Analyses revealed that meaning in life is a
significant mediator between perceived knowledge of stroke and depression ( z =
3.71, P < 0.001) and between perceived knowledge of stroke and life satisfaction
( z = 3.97, P < 0.001) in two separate models. CONCLUSION: The role of meaning in
life is clear and can affect the dynamics between knowledge of stroke and one's
psychological wellbeing.
PMID- 28516813
TI - Evidence based? Eminence based? We need both.
PMID- 28516812
TI - Hand surgery in Sweden.
PMID- 28516814
TI - British Society for Surgery of the Hand.
PMID- 28516817
TI - Decreased, but still sufficient, iodine intake of children and adults in the
Netherlands.
AB - Sufficient I intake is important for the synthesis of thyroid hormones, which
play an important role in normal growth and development. Our aim was to estimate
habitual I intake for the Dutch population and the risk of inadequate or
excessive intakes. Further, we aimed to provide an insight into the dietary
sources of I and the association with socio-demographic factors. Data from the
Dutch National Food Consumption Survey 2007-2010 (n 3819; 7-69 years), and from
the Dutch food and supplement composition tables were used to estimate habitual I
intake with a calculation model. Contribution of food groups to I intake were
computed and multiple linear regression was used to examine associations of
intakes with socio-demographic factors. A total of <=2 % of the population had an
intake below the estimated average requirement or above the upper level. The main
sources of I were bread containing iodised salt (39 %), dairy products (14 %) and
non-alcoholic drinks (6 %). I intake (natural sources only, excluding iodised
salt and supplements) was positively associated with (parental) education, which
could at least partly be attributed to a higher consumption of dairy products.
Among children, the consumption of bread, often containing iodised bakery salt,
was positively associated with parental education. The I intake of the Dutch
population (7-69 years) seems adequate, although it has decreased since the
period before 2008. With the current effort to reduce salt intake and changing
dietary patterns (i.e. less bread, more organic foods) it is important to keep a
close track on the I status, important sources and potential risk groups.
PMID- 28516819
TI - Temporal features of word-initial /s/+stop clusters in bilingual Mandarin-English
children and monolingual English children and adults.
AB - This study investigated the durational features of English word-initial /s/+stop
clusters produced by bilingual Mandarin (L1)-English (L2) children and
monolingual English children and adults. The participants included two groups of
five- to six-year-old bilingual children: low proficiency in the L2 (Bi-low) and
high proficiency in the L2 (Bi-high), one group of age-matched English children,
and one group of English adults. Each participant produced a list of English
words containing /sp, st, sk/ at the word-initial position followed by /a, i, u/,
respectively. The absolute durations of the clusters and cluster elements and the
durational proportions of elements to the overall cluster were measured. The
results revealed that Bi-high children behaved similarly to the English
monolinguals whereas Bi-low children used a different strategy of temporal
organization to coordinate the cluster components in comparison to the English
monolinguals and Bi-high children. The influence of language experience and
continuing development of temporal features in children were discussed.
PMID- 28516818
TI - The changing epidemiology of spinal tuberculosis: the influence of international
immigration in Catalonia, 1993-2014.
AB - The overall incidence of spinal tuberculosis (TB) appears to be stable or
declining in most European countries, but with an increasing proportion of cases
in the foreign-born populations. We performed a retrospective observational study
(1993-2014), including all cases of spinal TB diagnosed at a Barcelona hospital
to assess the epidemiological changes. Fifty-four episodes (48.1% males, median
age 52 years) of spinal TB were diagnosed. The percentage of foreign-born
residents with spinal TB increased from 14% to 45.2% in the last 10 years (P =
0.017). Positive Mycobacterium tuberculosis testing in vertebral specimens was
88.2% (15/17) for GeneXpert MTB/RIF. Compared with natives, foreign-born patients
were younger (P < 0.01) and required surgery more often (P = 0.003) because of
higher percentages of paravertebral abscess (P = 0.038), cord compression (P =
0.05), and persistent neurological sequelae (P = 0.05). In our setting, one-third
of spinal TB cases occurred in non-native residents. Compared with natives,
foreign-born patients were younger and had greater severity of the disease. The
GeneXpert MTB/RIF test may be of value for diagnosing spinal TB.
PMID- 28516820
TI - Blogging in Infectious Diseases and Clinical Microbiology: Assessment of
'Blogosphere' Content.
AB - OBJECTIVE To analyze influential infectious diseases, antimicrobial stewardship,
infection control, or medical microbiology blogs and bloggers SETTING World wide
web DESIGN We conducted a systematic search for blogs in accordance with the
PRISMA guidelines in September 2015. METHODS A snowball sampling approach was
applied to identify blogs using various search engines. Blogs were eligible if
they (1) focused on infectious diseases, antimicrobial stewardship, infection
control, or medical microbiology; (2) were intended for health professionals; and
(3) were written in English and (4) were updated regularly. We mapped blog and
blogger characteristics and used an innovative tool to assess the architecture
and content of the included blogs. The motivations and perceptions of bloggers
and readers were also assessed. RESULTS A total of 88 blogs were identified.
Moreover, 28 blogs (32%) focused on infectious diseases, 46 (52%) focused on
medical microbiology, and 14 (16%) focused on infection control or antimicrobial
stewardship. Bloggers were mainly male with medical doctorates and/or PhDs; 32
bloggers (36%) posted at least weekly; and 51 (58%) had a research purpose. The
aims were considered clear for 23 blogs (26%), and the field covered was
considered broad for 25 blogs (28%). Presentation was considered good for 22
blogs (25%), 51 blogs (58%) were easy to read, and 46 blogs (52%) included expert
interpretation. Among the top 10 blogs, 3 focused on infectious diseases, 6
focused on medical microbiology, and 2 focused on infection control (2 were
equally ranked). The bloggers we questioned were motivated to share their
independent expertise and opinions. Readers appreciated the concise messages on
scientific topics and practical updates. CONCLUSIONS This study describes high
level blogs in the fields of infectious diseases, infection control, and medical
microbiology. Our findings suggest ways in which bloggers should build/orientate
blogs for readers, and we have highlighted current gaps in blog topics such as
antimicrobial stewardship. Infect. Control Hosp. Epidemiol 2017;38:832-839.
PMID- 28516821
TI - Pseudomonas aeruginosa Outbreak in a Neonatal Intensive Care Unit Attributed to
Hospital Tap Water.
AB - OBJECTIVE To investigate an outbreak of Pseudomonas aeruginosa infections and
colonization in a neonatal intensive care unit. DESIGN Infection control
assessment, environmental evaluation, and case-control study. SETTING Newly built
community-based hospital, 28-bed neonatal intensive care unit. PATIENTS Neonatal
intensive care unit patients receiving care between June 1, 2013, and September
30, 2014. METHODS Case finding was performed through microbiology record review.
Infection control observations, interviews, and environmental assessment were
performed. A matched case-control study was conducted to identify risk factors
for P. aeruginosa infection. Patient and environmental isolates were collected
for pulsed-field gel electrophoresis to determine strain relatedness. RESULTS In
total, 31 cases were identified. Case clusters were temporally associated with
absence of point-of-use filters on faucets in patient rooms. After adjusting for
gestational age, case patients were more likely to have been in a room without a
point-of-use filter (odds ratio [OR], 37.55; 95% confidence interval [CI], 7.16
infinity). Case patients had higher odds of exposure to peripherally inserted
central catheters (OR, 7.20; 95% CI, 1.75-37.30) and invasive ventilation (OR,
5.79; 95% CI, 1.39-30.62). Of 42 environmental samples, 28 (67%) grew P.
aeruginosa. Isolates from the 2 most recent case patients were indistinguishable
by pulsed-field gel electrophoresis from water-related samples obtained from
these case-patient rooms. CONCLUSIONS This outbreak was attributed to
contaminated water. Interruption of the outbreak with point-of-use filters
provided a short-term solution; however, eradication of P. aeruginosa in water
and fixtures was necessary to protect patients. This outbreak highlights the
importance of understanding the risks of stagnant water in healthcare facilities.
Infect Control Hosp Epidemiol 2017;38:801-808.
PMID- 28516822
TI - Key drivers of patient experience in ambulatory paediatric cardiology.
AB - Patient experience is becoming a central focus of healthcare. A broad range of
studies on how to increase patient satisfaction ratings exists; however, they
lack the specificity to adequately guide physicians and hospitals on how to
improve patient experience. The objective of this study was to define the aspects
of patient experience within paediatric cardiologist practices that can serve as
predictors of excellent patient satisfaction. From 1 January, 2013 to 28
February, 2015 (26 months), outpatients who visited paediatric cardiologists were
asked to complete a 39-question patient satisfaction survey regarding their
experience. Surveys were collected over a 26-month period by Press Ganey, an
independent provider of patient satisfaction surveys. Participants were asked to
rate their experience on a 1-5 Likert-scale: a score of 1 demonstrated a "poor"
experience, whereas a score of 5 demonstrated a "very good" experience. This
retrospective study of 2468 responses determined that cheerfulness of the
practice (r=0.85, p<0.001), a cohesive staff (r=0.83, p<0.001), and a care
provider explaining problems and conditions (r=0.81, p<0.001) were key aspects of
a paediatric cardiologist's practice that can be used as predictors of overall
patient satisfaction. Awareness of how doctors can personalise a patient's
experience is vital to achieve greater patient satisfaction and, ultimately,
better patient outcomes.
PMID- 28516824
TI - Opinion paper: Smell: an affordable way to improve livestock welfare.
PMID- 28516823
TI - Predictors of health-related quality of life in children with chronic heart
disease.
AB - OBJECTIVE: Chronic paediatric heart disease is often associated with residual
symptoms, persisting functional restrictions, and late sequelae for psychosocial
development. It is, therefore, increasingly important to evaluate the health
related quality of life of children and adolescents with chronic heart disease.
The aim of this study was to determine medical and socio-demographic variables
affecting health-related quality of life in school-aged children and adolescents
with chronic heart disease. Patients and methods The Pediatric Cardiac Quality of
Life Inventory was administered to 375 children and adolescents and 386 parental
caregivers. Medical information was obtained from the charts. The socio
demographic information was provided by the patients and caregivers. RESULTS:
Greater disease severity, low school attendance, current cardiac medication,
current parental employment, uncertain or limited prognosis, history of
connection to a heart-lung machine, number of nights spent in a hospital, and
need for treatment in a paediatric aftercare clinic independently contributed to
lower health-related quality of life (self-report: R2=0.41; proxy-report:
R2=0.46). High correlations between self-reports and parent-proxy reports
indicated concordance regarding the evaluation of a child's health-related
quality of life. CONCLUSIONS: Beyond medical treatment, integration into school
is important to increase health-related quality of life in children and
adolescents surviving with chronic heart disease. Regular screening of health
related quality of life is recommended to identify patients with special needs.
PMID- 28516825
TI - Girls' and boys' trajectories of appearance anxiety from age 10 to 15 years are
associated with earlier maturation and appearance-related teasing.
AB - Adolescents' appearance-related concerns can provoke increasing emotional,
social, and eating-related problems. The aims of this five-wave (2.5-year),
multiple-informant longitudinal study were to (a) examine growth trajectories of
appearance anxiety symptoms and appearance esteem, (b) identify whether
trajectories differed by gender, and (c) examine several launching factors
including parent-reported physical maturation, peer-rated physical appearance,
body mass index, and appearance teasing by parents and peers. Participants were
387 adolescents (44% boys) aged 10 to 13 years at the first assessment. Steep
growth in appearance anxiety symptoms was found for both girls and boys, but
there was no average change in appearance esteem. Girls had more elevated
appearance anxiety symptoms and lower appearance esteem than boys, girls' body
mass index was associated with symptoms, and earlier physical maturation and
teasing about appearance, alone and in combination, were associated with growth
in appearance anxiety symptoms for girls and boys. Earlier maturing boys who were
highly teased by parents, but even more so when teased by peers, were at utmost
risk for elevated appearance anxiety symptoms and increasing symptoms over time.
In contrast, all girls exhibited elevated or increasing appearance anxiety
symptoms across time, with the exception of girls with the latest maturation who
also reported little teasing about their appearance.
PMID- 28516827
TI - BOLD activation of the ventromedial prefrontal cortex in patients with late life
depression and comparison participants.
AB - ABSTRACTThe ventromedial prefrontal cortex's (vMPFC) role in regulating emotions
in late life depression (LLD) remains unclarified. We assessed vMPFC activation
in an emotional valence blood oxygenation level-dependent (BOLD) functional
magnetic neuroimaging (fMRI) task and related the findings to extent of white
matter hyperintensities (WMH). Sixteen participants with mild to moderate LLD
were compared to 14 similar aged comparison participants. Participants in the
scanner viewed words matched for length and arousal, indicated the perceived
valence by pressing one of the three buttons i.e. "positive, negative, or
neutral." WMH volume was greater in LLD participants than comparison
participants. There were no differences in activations between groups to any
valence contrast. Female LLD participants showed greater activation for negative
versus positive and negative versus neutral words as compared to female
comparison participants. Female LLD participants respond differently to
emotionally laden words compared to comparison participants. WMH could play a
role in etiopathology of emotional perception in female LLD participants.
PMID- 28516826
TI - Fatalities from Firearm-Related Injuries in Selected Governorates of Iraq, 2010
2013.
AB - BACKGROUND: In Iraq, where Islamic State of Iraq and Syria (ISIS) and other
groups have contributed to escalating violence in recent years, understanding the
epidemiology of intentional firearm-related fatalities is essential for public
health action. METHODS: The Iraqi Ministry of Health (MoH; Baghdad, Iraq)
compiles surveillance of fatal injuries in eight of Iraq's 18 governorates
(Baghdad, Al-Anbar, Basrah, Erbil, Kerbala, Maysan, Ninevah, and Al-Sulaimaniya).
Information is collected from coroner's reports and interviews with family
members. Analysis was performed on intentional firearm-related injuries,
excluding injuries from intentional self-harm or negligent discharges, that
occurred during 2010-2013, a subset of all fatal injuries, and compared to
previously published explosive-related fatalities. RESULTS: Overall, the dataset
included 7,985 firearm-related fatalities. Yearly fatalities were: 2010=1,706;
2011=1,642; 2012=1,662; and 2013=2,975. Among fatalities, 86.0% were men and
13.7% women; 83.4% were adults and 6.2% children <18 years of age. Where age and
sex were both known, men aged 20-39 years accounted for 56.3% of fatalities.
Three "high-burden" governorates had the highest fatality rate per 100,000
population-Baghdad (12.9), Ninevah (17.0), and Al-Anbar (14.6)-accounting for
85.9% of fatalities recorded in the eight governorates. Most fatalities occurred
in the street (56.3%), followed by workplace (12.2%), home (11.3%), and
farm/countryside (8.4%). Comparing the ratio of firearm-related fatalities to
explosives-related fatalities revealed an overall ratio of 2.8:1. The ratio in
Baghdad more than doubled from 2.9 in 2010 to 6.1 in 2013; the highest ratios
were seen outside the high-burden governorates. CONCLUSIONS: Firearm-related
fatalities remained relatively stable throughout 2010-2012, and almost doubled in
2013, correlating with increased ISIS activity. Three governorates contributed
the majority of fatalities and experienced the highest fatality rates; these saw
high levels of conflict. Firearm-related fatalities disproportionately affected
younger men, who historically are over-represented as victims and perpetrators of
violence. More than one-half of fatalities occurred in the street, indicating
this as a common environment for conflict involving firearms. Firearms appear to
account for more fatalities in Iraq than explosives and largely accounted for
escalating violence in Baghdad during the study period. The high ratio observed
outside the high-burden governorates is reflective of very low numbers of
explosives-related fatalities; thus, violence in these governorates is likely non
conflict-related. These observations provide valuable public health information
for targeted intervention to prevent violence. Nerlander MP , Leidman E , Hassan
A , Sultan ASS , Hussain SJ , Browne LB , Bilukha OO . Fatalities from firearm
related injuries in selected governorates of Iraq, 2010-2013. Prehosp Disaster
Med. 2017;32(5):548-555.
PMID- 28516828
TI - Impact on the medical decision-making process of multiplex PCR assay for
respiratory pathogens.
AB - The objective of this study was to determine how clinicians make use of the
modern multiplex PCR assays (MPAs) to manage patients hospitalized for community
acquired pneumonia (CAP). We studied the use of MPAs in 1648 patients
hospitalized for CAP over a 3-year period at the moment of the setup of the new
PCR assay. We observed that the use of MPAs for the identification of multiple
respiratory pathogens marks a radical change in the investigation of CAP
etiology. Surprisingly, the contribution of MPAs to the medical decision-making
process varies drastically according to the units of care.
PMID- 28516829
TI - Factors associated with failure of emergency wait-time targets for high acuity
discharges and intensive care unit admissions.
AB - OBJECTIVE: Ontario established emergency department length-of-stay (EDLOS)
targets but has difficulty achieving them. We sought to determine predictors of
target time failure for discharged high acuity patients and intensive care unit
(ICU) admissions. METHODS: This was a retrospective, observational study of 2012
Sunnybrook Hospital emergency department data. The main outcome measure was
failing to meet government EDLOS targets for high acuity discharges and ICU
emergency admissions. The secondary outcome measures examined factors for low
acuity discharges and all admissions, as well as a run chart for 2015 - 2016 ICU
admissions. Multiple logistic regression models were created for admissions, ICU
admissions, and low and high acuity discharges. Predictor variables were at the
patient level from emergency department registries. RESULTS: For discharged high
acuity patients, factors predicting EDLOS target failure were having physician
initial assessment duration (PIAD)>2 hours (OR 5.63 [5.22-6.06]), consultation
request (OR 10.23 [9.38-11.14]), magnetic resonance imaging (MRI) (OR 19.33
[12.94-28.87]), computed tomography (CT) (OR 4.24 [3.92-4.59]), and ultrasound
(US) (OR 3.47 [3.13-3.83]). For ICU admissions, factors predicting EDLOS target
failure were bed request duration (BRD)>6 hours (OR 364.27 [43.20-3071.30]) and
access block (AB)>1 hour (OR 217.27 [30.62-1541.63]). For discharged low acuity
patients, factors predicting failure for the 4-hour target were PIAD>2 hours (OR
15.80 [13.35-18.71]), consultation (OR 20.98 [14.10-31.22]), MRI (OR 31.68 [6.03
166.54]), CT (OR 16.48 [10.07-26.98]), and troponin I (OR 13.37 [6.30-28.37]).
CONCLUSION: Sunnybrook factors predicting failure of targets for high acuity
discharges and ICU admissions were hospital-controlled. Hospitals should
individualize their approach to shortening EDLOS by analysing its patient
population and resource demands.
PMID- 28516830
TI - Childhood Victimization, Attachment, Coping, and Substance Use Among Victimized
Women on Probation and Parole.
AB - Justice-involved women report high rates of victimization across their life span,
and these experiences contribute to their involvement in the criminal justice
(CJ) system. Within this population, research has identified an overlap among
victimization and substance use, a high-risk coping mechanism. Furthermore,
research indicates attachment style is related to coping and high-risk behaviors.
Research is needed to understand the relationship among these mechanisms as they
relate to intimate partner violence (IPV). To address this gap, this study
investigated the relationship between attachment, coping, childhood
victimization, substance use, and IPV among 406 victimized women on
probation/parole. Results of 6 multivariate regression analyses were
statistically significant, accounting for 8%-13% of the variance in IPV.
Particularly, childhood sexual victimization and negative coping were significant
in all analyses. Findings provide practitioners, administrators, and policymakers
information about the specific needs of justice-involved women.
PMID- 28516831
TI - An Exploration of the Mediators Between Childhood Maltreatment and Intimate
Partner Violence.
AB - Intimate partner violence (IPV) is associated with numerous long-term
consequences and warrants significant clinical attention. Recent theoretical
models and empirical research have suggested that several factors play a role in
the development of IPV perpetration, including childhood maltreatment, early
maladaptive schemas, anger, and difficulties in emotion regulation. This study
investigated the relationship between childhood maltreatment and IPV,
specifically examining the mediation of this relationship by several variables
thought to be related to this pernicious problem, including early maladaptive
schemas, the experience of anger, and emotion regulation difficulties. In a young
adult collegiate sample of 110 women in relationships, results of a bootstrapped
multiple mediation analysis supported the hypothesis that childhood maltreatment
predicted physical aggression within intimate partner relationships and found
that the total indirect effect of childhood maltreatment on physical aggression
through the 3 proposed mediators was significant. However, consistent with recent
empirical findings, only difficulties in emotion regulation significantly
mediated the relationship between childhood maltreatment and physical aggression
within the sample.
PMID- 28516832
TI - The Neighborhood Context of Hate Crime: A Comparison of Violent and Property
Offenses Using Rare Events Modeling.
AB - Many studies into the antecedents of hate crime in the neighborhood combine
offense categories, meaning that it is unclear whether or not there are distinct
contextual factors associated with violent and property hate offenses. This study
uses rare events modeling to examine the household and neighborhood factors
associated with violent and property offenses. Using the Australian Community
Capacity Study, the study focuses on the neighborhood characteristics influencing
self-reported violent and property hate crime for 4,396 residents in Brisbane.
Findings demonstrate important differences between the offense types. Violence is
predicted by household renting and non-English language, whereas property
offenses are predicted by household non-English language, neighborhood median
income, and change in non-English-speaking residents. In both offense types,
neighborhood place attachment acts as a protective factor. These findings
highlight the theoretical implications of combining distinct hate crime types for
methodological reasons.
PMID- 28516835
TI - Modifying Self-Blame, Self-Esteem, and Disclosure Through a Cooperative Cross-Age
Teaching Intervention for Bullying Among Adolescents.
AB - Bullying is common among school students, and some victims hold self-blaming
attributions, exhibit low self-esteem, and do not seek social support. A wait
list control pre-/post-test experimental design, with random allocation, was used
to assess the effects of a novel cross-age teaching of social issues (CATS)
intervention on the latter 3 variables among peer-identified victims of bullying
(N = 41, mean age = 14.5 years). In small cooperative groups of classmates,
participants designed and delivered a lesson to younger students that informed
them that bullies not victims are in the wrong, victims have no reason to feel
bad about themselves, and that seeking help can be beneficial. CATS led to a
significant improvement on all 3 dependent variables with mostly large effect
sizes; these positive effects were even stronger with a bigger dose of
intervention (6 hr vs. 4 hr), and changes in self-blame, and separately changes
in self-esteem, mediated the positive effect of the intervention on help-seeking.
The theoretical and practical implications of these results were discussed,
especially in terms of supporting a highly vulnerable subgroup of adolescents.
PMID- 28516836
TI - A Review and Assessment of Intimate Partner Violence Interventions and Trainings
for Service Providers and Frontline Staff.
AB - Despite a long history of various service providers' interactions with the
survivors of intimate partner violence (IPV), previous reviews of interventions
for service providers addressing IPV have only focused on those employed in
medical settings. This review closely examines evidence related to interventions
for service providers and frontline staff in nonmedical settings to identify
effective interventions to address IPV and assist IPV survivors. Using explicit
criteria, 16 studies were included in this review. This review offers a synthesis
of the 16 studies by illuminating types of the interventions, outcomes and their
effectiveness, settings of the interventions, and their quality of design.
Specific implications are discussed to guide future practice, research, and
policy.
PMID- 28516837
TI - Help-Seeking Behavior Among Moroccan, Romanian, and Ecuadorian Women Experiencing
Intimate Partner Violence in Spain.
AB - This study aims to identify different types of response to intimate partner
violence (IPV) and help-related seeking behavior among Spain's most numerous
immigrant groups-Moroccans, Romanians, and Ecuadorians. Women reporting physical,
sexual and/or psychological violence by a current or former intimate partner (n =
194) were selected from a cross-sectional study based on 1,607 surveys (2011).
There are 84% of surveyed battered women who reported seeking help through
informal and/or formal channels. The most frequently reported informal help
seeking behavior was talking with the abusive partner (from 63% to 83%).
Moroccans identified social services (29.6%) and health care (25.9%)
professionals as their most frequently used formal resources when seeking help.
Approximately 32% of Ecuadorians and Romanians declared having reported their
partners to the police. Among all of the women, seeking help through formal
channels was more probable in cases where the severity of IPV was high (adjusted
odds ratio = 5.69, 95% confidence interval [2.29, 14.12]). It is needed to
increase professionals' opportunities to intervene in cases of IPV before they
become severe.
PMID- 28516838
TI - Acute Alcohol Use, History of Homelessness, and Intent of Injury Among a Sample
of Adult Emergency Department Patients.
AB - BACKGROUND: The literature is clear that adults who are currently homeless also
have higher rates of intentional injuries, such as assault and suicide attempts.
No study has assessed whether intentional injuries are exacerbated because of
substance use among adults with a history of homelessness. METHODS: Data were
obtained from a cohort of adults admitted to 3 urban emergency departments (EDs)
in Texas from 2007 to 2010 (N = 596). Logistic regression analyses were used to
determine whether a history of homelessness was associated with alcohol use at
time of injury in intentional violent injuries (gunshot, stabbing, or injury
consistent with assault). RESULTS: 39% adults with a history of homelessness who
were treated at trauma centers for a violent injury. Bivariate analyses indicated
that adults who had ever experienced homelessness have 1.67 increased odds, 95%
confidence interval (CI) [1.11, 2.50], of any intentional violent injury and 1.95
increased odds (95% CI [1.12, 3.40]) of a stabbing injury than adults with no
history of homelessness. CONCLUSIONS: Adults who experienced homelessness in
their lifetime were more likely to visit EDs for violencerelated injuries. Given
our limited knowledge of the injuries that prompt ED use by currently homeless
populations, future studies are needed to understand the etiology of injuries,
and substance-related injuries specifically, among adults with a history of
homelessness.
PMID- 28516839
TI - Ethno-Racial Differences in Children's Attitudes and Beliefs About Violence.
AB - One in 15 children in the United States are exposed to intimate partner violence
(IPV) each year. Although much is known about the adverse effects of witnessing
IPV on children, little attention has been given to the impact of IPV on children
of diverse ethno-racial backgrounds. In particular, the association between IPV
and children's attitudes and beliefs about violence across different ethno-racial
populations remains to be explored. One hundred ninety children between the ages
of 4 and 12 years of varying ethno-racial backgrounds who had witnessed recent
IPV were interviewed regarding their attitudes and beliefs about IPV. Results
show that younger children and White, Black, and Biracial children exhibited more
deleterious attitudes and beliefs about violence after exposure to IPV than did
older and Latina or Latino children. These findings may indicate the need for
more tailored intervention programs that target the specific maladaptive beliefs
expressed by children of various demographic groups.
PMID- 28516841
TI - Us3 and Us9 proteins contribute to the stromal invasion of bovine herpesvirus 1
in the respiratory mucosa.
AB - Bovine herpesvirus 1 (BHV-1) infection may lead to conjunctivitis, upper
respiratory tract problems, pneumonia, genital disorders and abortion. BHV-1 is
able to spread quickly in a plaque-wise manner and invade by breaching the
basement membrane (BM) barrier in the respiratory mucosa. BHV-1 Us3, a
serine/threonine kinase, induces a dramatic cytoskeletal reorganization and BHV-1
Us9, a tail-anchored membrane protein, is required for axonal transport of
viruses in neurons. In this study, we investigated the role of Us3 and Us9 during
BHV-1 infection in the respiratory mucosa. First, we constructed and
characterized BHV-1 Us3 null, Us9 null and revertant viruses. Then, we analysed
the viral replication and plaque size (latitude) in Madin-Darby bovine kidney
(MDBK) cells and the respiratory mucosa as well as viral penetration depth
underneath the BM of the respiratory mucosa when inoculated with these
recombinant viruses. Knockout of Us3 resulted in a 1 log10 reduction in viral
titre and plaque size (latitude) in MDBK cells and the trachea mucosa. There were
no defects in the cell-to-cell spread observed for BHV-1 Us9 null virus. Both BHV
1 Us3 null and Us9 null viruses showed a significant reduction of plaque
penetration underneath the BM; however, penetration was not completely inhibited.
In conclusion, the current findings demonstrated that Us3 and Us9 play an
important role in the invasion of BHV-1 through the BM of the respiratory mucosa,
which shows the way forward for research-based attenuation of viruses in order to
make safer and better-performing vaccines.
PMID- 28516840
TI - Victim Alcohol Intoxication During a Sexual Assault: Relations With Subsequent
PTSD Symptoms.
AB - This study examines associations between women's alcohol intoxication at the time
of sexual assault and posttraumatic stress disorder (PTSD) symptoms. Drawing on
the dual representation theory (Brewin, Gregory, Lipton, & Burgess, 2010), we
hypothesized that intoxication at the time of assault would be positively
associated with both overall symptoms of PTSD and PTSD reexperiencing symptoms in
particular. A total of 143 community women (ages 18-26 years; 71.3% European
American) reporting sexual victimization completed questionnaires assessing
severity of coercion involved in the assault, perceived level of intoxication at
the time of assault, and current PTSD symptoms. Overall, results suggested that
greater alcohol intoxication (but not alcohol use alone) was associated with more
severe PTSD symptoms when controlling for severity of coercion. Furthermore,
higher levels of victim intoxication at the time of the assault were most
predictive of reexperiencing symptoms relative to the other symptom clusters.
PMID- 28516842
TI - Serotype distribution, antimicrobial resistance and prevalence of pilus islets in
pneumococci following the use of conjugate vaccines.
AB - PURPOSE: In Japan, the 7-valent pneumococcal vaccine (PCV7) was introduced in
2010 and, in 2013, the PCV7 was replaced with the 13-valent pneumococcal vaccine
(PCV13). This study was conducted to investigate serotypes, antimicrobial
resistance and prevalence of pilus islets in pneumococcal isolates from
inpatients in a Japanese tertiary hospital. METHODOLOGY: From April 2011 to
February 2016, 151 isolates [95 (18 children, 77 adults) and 56 (19 children, 37
adults) in the PCV7 and PCV13 periods, respectively] were collected. All isolates
were serotyped using genetic methods and were tested for susceptibility to 18
antimicrobials. Unaltered penicillin-binding protein (PBP) genes, macrolide
resistance genes and pilus islets were identified by PCR. RESULTS: Between the
two periods, the prevalence of non-PCV13 serotypes was shown to increase from
50.0 to 78.9 % in children, and serotype 3 increased from 14.3 to 24.3 % in
adults. Six of seven isolates from invasive diseases were assigned to non-PCV13
serotypes. Overall, multidrug resistance (MDR) was detected in 46.4 % of
isolates, which included the dominant non-PCV13 serotypes 6E, 15A and 23A
(prevalence>=75.0 %). gPRSP (three altered genes pbp1a, pbp2b and pbp2x) and
macrolide resistance genes [erm(B) and/or mef(A/E)] were detected in 35.8 and
93.4 % of all isolates, respectively. Pilus islets [PI-1 (clade I, II and III)
and/or PI-2] were found in 22.5 % (34/151) of isolates belonging to six different
serotypes (19F, 23F, 19A, 6E, 15B and 35B) and 88.2 % (30/34) of these exhibited
MDR. CONCLUSION: This study revealed the spread of MDR in several non-PCV13
serotypes and in isolates with pilus islets.
PMID- 28516843
TI - Potentially hazardous Streptococcus suis strains latent in asymptomatic pigs in a
major swine production area of Thailand.
AB - PURPOSE: Carrier pigs have been considered as the major reservoir of
Streptococcus suis and couldbe a significant source of human infection.
Therefore, we investigated the prevalence and characteristics of latent S. suis
in asymptomatic pigs in the pig-farming area of central Thailand, and compared
the data to those previously reported in other regions. METHODOLOGY: We collected
samples from 340 asymptomatic pigs. S. suis isolates from the samples were
confirmed by species-specific PCR (recN PCR). The capsular polysaccharide
synthesis gene (cps) types, virulence-associated gene profiles and sequence types
(STs) of the isolates were investigated.Results/Key findings. The prevalence of
S. suis found in this study was 37 % (125/340 pigs). The most prevalent genotype
was mrp-/epf-/sly-. Among the 16 cps-types identified in 135 isolates, cps-type
16 was the most frequent (11 %), whereas 44 % of the isolates were non-typable.
In common with the strains causing human sepsis in Thailand, two cps-type 9
isolates and a cps-type 24 isolate from slaughtered pigs belonged to ST16 and
ST221, respectively. All the isolated cps-type 2 strains were confirmed as
serotype 2 by co-agglutination tests, and these belonged to ST104, the unique ST
commonly found in Thai patients; however, in contrast to the endemic areas, the
prevalence of serotype 2 strains was relatively low (2 %) and no ST1 isolate was
found. CONCLUSION: Our results showed the population structure differences
between S. suis in central Thailand and other regions; however, zoonotic S. suis
is certainly latent in asymptomatic pigs in this intensive swine production area.
PMID- 28516845
TI - Activity and functional properties of the isocitrate lyase in the cyanobacterium
Cyanothece sp. PCC 7424.
AB - Cyanobacteria are ubiquitous photoautotrophs that assimilate atmospheric CO2 as
their main source of carbon. Several cyanobacteria are known to be facultative
heterotrophs that are able to grow on diverse carbon sources. For selected
strains, assimilation of organic acids and mixotrophic growth on acetate has been
reported for decades. However, evidence for the existence of a functional
glyoxylate shunt in cyanobacteria has long been contradictory and unclear. Genes
coding for isocitrate lyase (ICL) and malate synthase were recently identified in
two strains of the genus Cyanothece, and the existence of the complete glyoxylate
shunt was verified in a strain of Chlorogloeopsis fritschii. Here, we report that
the gene PCC7424_4054 of the strain Cyanothece sp. PCC 7424 encodes an
enzymatically active protein that catalyses the reaction of ICL, an enzyme that
is specific for the glyoxylate shunt. We demonstrate that ICL activity is induced
under alternating day/night cycles and acetate-supplemented cultures exhibit
enhanced growth. In contrast, growth under constant light did not result in any
detectable ICL activity or enhanced growth of acetate-supplemented cultures.
Furthermore, our results indicate that, despite the presence of a glyoxylate
shunt, acetate does not support continued heterotrophic growth and cell
proliferation. The functional validation of the ICL is supplemented with a
bioinformatics analysis of enzymes that co-occur with the glyoxylate shunt. We
hypothesize that the glyoxylate shunt in Cyanothece sp. PCC 7424, and possibly
other nitrogen-fixing cyanobacteria, is an adaptation to a specific ecological
niche and supports assimilation of nitrogen or organic compounds during the night
phase.
PMID- 28516846
TI - Revealing Victimization: The Impact of Methodological Features in the National
Crime Victimization Survey.
AB - This study examines the impact of methodological features of the National Crime
Victimization Survey (NCVS) on respondent willingness to report violent, serious
violent, and property victimizations to the NCVS. Bounded and unbounded data from
the 1999-2005 NCVS are used to create a longitudinal file of respondents, and
survey-weighted logistic regression models are used to assess the factors
associated with the reporting of victimization. Net of sociodemographic control
variables, unbounded interviews produced higher estimates of serious violence
(72%), violence (66%), and property victimization (67%). Mobile respondents
reported higher estimates than nonmobile respondents of serious violence (48%),
violence (35%), and property victimization (15%). Compared with in-person
interviews, interviewing by telephone increased reporting for serious violence
(7%), violence (12%), and property victimization (17%). This study highlights the
importance of controlling for these factors in both longitudinal and cross
sectional analyses to estimate victimization risk.
PMID- 28516844
TI - Clues for two-step virion infectivity factor regulation by core binding factor
beta.
AB - Lentiviruses threaten human and animal health. Virion infectivity factor (Vif) is
essential for the infectivity of most lentiviruses, except for the equine
infectious anaemia virus (EIAV). Vif promotes viral infectivity by recruiting a
Cullin-based E3 ligase to induce the degradation of a class of host restriction
factors, named APOBEC3. Core binding factor beta (CBF-beta) is necessary for
several primate lentiviral Vif functions, including HIV-1 Vif. Although much
progress has been made in understanding the contribution of CBF-beta to Vif
function, the precise mechanism has not yet been fully elucidated. In this study,
we found that an interaction with CBF-beta altered the oligomerization and
subcellular distribution pattern and increased the stability of two primate
lentiviral Vifs, HIV-1 Vif and Macaca simian immunodeficiency virus (SIVmac) Vif.
Moreover, using a CBF-beta loss-of-function mutant, we demonstrated that the
interaction between CBF-beta and Vif was not sufficient for Vif assistance; a
region including F68 in CBF-beta was also required for the stability and function
of Vif. For the first time, this study separates the binding and regulating
processes of CBF-beta when it is promoting Vif function, which further extends
our understanding of the biochemical regulation of Vif by CBF-beta.
PMID- 28516848
TI - The Role of Psychopathic Traits in Female Sexual Coercion.
AB - Researchers have consistently found a relationship between psychopathy and the
use of sexual coercion in samples of males with and without previous sexual
arrests (Abbey, Jacques-Tiura, & LeBreton, 2011; Hare, 1991; Hersh & Gray-Little,
1998; Seto & Lalumiere, 2000). Although there is growing recognition that females
also engage in sexually coercive behavior, current understanding of female
coercion is limited (Bouffard, Bouffard, & Miller, 2015; Cortoni, Hanson, &
Coache, 2010; Munoz, Khan, & Cordwell, 2011). This study examined the
relationship between psychopathic traits and sexual coercion tactics among a
sample of 558 undergraduate females. Results indicate that the use of any
previous sexual coercion tactic (coax, lie, get drunk, and assault) and higher
endorsement of primary psychopathy traits significantly predict whether the
females state that they will engage in future sexually coercive behaviors.
PMID- 28516847
TI - Who Is at Risk for Intimate Partner Violence Victimization: Using Latent Class
Analysis to Explore Interpersonal Polyvictimization and Polyperpetration Among
Pregnant Young Couples.
AB - The purpose of our study was (a) to use latent class analyses to identify
subgroups of interpersonal polyvictimization and polyperpetration among young
pregnant couples and (b) examine actor-partner effects of latent classes on
current intimate partner violence (IPV) victimization. Data were collected from
296 pregnant young couples recruited at obstetrics and gynecology clinics. A 3
latent class model emerged for women: Polyvictim-Polyperpetrator, Nonvictim
Nonperpetrator, and Community and Prior IPV Victim. A 4-latent class model
emerged for men: Community and Prior IPV Victim, Polyvictim-Nonpartner
Perpetrator, Prior IPV and Peer Victim, and Nonvictim-Nonperpetrator. Using the
actor-partner independence model, actor effects of the women's Polyvictim
Polyperpetrator class and men's Polyvictim-Nonpartner Perpetrator class related
to greater odds of IPV victimization compared to women and men in the Nonvictim
Nonperpetrator classes.
PMID- 28516849
TI - Identification of Nonfatal Strangulation by 911 Dispatchers: Suggestions for
Advances Toward Evidence-Based Prosecution.
AB - Research highlights the need for systematic law enforcement training on nonfatal
strangulation in domestic violence situations to improve evidence-based
prosecution of these violent felonies. However, most of this research focuses on
the role of police officers in the safety response. Although often overlooked,
this research examines the role of 911 dispatchers, who are many times the first
person the victim calls for assistance. This study examines official domestic
violence records, gathered through a partnership with a County Sheriff's agency,
to determine whether domestic violence strangulation is being adequately
identified and documented by first responders. This research highlights the need
for considering 911 dispatchers as having a potentially critical role in a
comprehensive response to domestic violence strangulation from initial screening
to eventual prosecution.
PMID- 28516850
TI - Are Men With a History of Head Injury Less Responsive to Cognitive Behavioral
Therapy for Intimate Partner Violence?
AB - Head injury is highly prevalent among intimate partner violence (IPV) offenders.
This study investigates responsiveness to cognitive behavioral therapy (CBT) for
partnerviolent men with and without a history of head injury using archival data
on 310 males seeking IPV counseling at a community domestic violence agency.
Participants reported on their history of head injury, age at injury, and length
of time unconscious in a structured interview at program intake. Criminal justice
outcomes were assessed for the 2-year period after scheduled completion of
treatment using a publicly available state database. A significantly greater
percentage of men with a history of head injury (N = 84) than those without (N =
226) had criminal involvement for incidents of partner abuse during the follow-up
period. In addition, men with a history of moderate-to-severe head injury (n =
25) had more criminal involvement for general violence than those with no history
of head injury. The findings highlight the need to screen partner-violent men for
head injury and to develop and investigate intervention enhancements for those
individuals.
PMID- 28516851
TI - Intimate Partner Abuse and Attachment: A Comparison Between Abused and Nonabused
Women.
AB - The purpose of this study was to examine intimate partner abuse (IPA), parental
attachment, and romantic attachment among college women. More specifically, IPA
was examined such that women who had experienced abuse and those who had not were
compared with respect to parental and romantic attachment using the lens of
attachment theory. Undergraduate women (N = 502) completed an online survey
assessing their experiences of IPA as well as their parental and romantic
attachment styles. Bivariate correlations demonstrated that IPA was significantly
associated with all study variables (i.e., love withdrawal, care, and
overprotection from both mother and father; romantic anxiety) in the hypothesized
directions with the exception of romantic avoidance not being associated with
abuse. Regarding the comparison of women who had experienced abuse (n = 367) to
women who had not experienced abuse (n = 135), one-way analyses of variance
(ANOVAs) revealed significant group mean differences in the hypothesized
directions between abused and nonabused women with respect to love withdrawal and
overprotection from both mothers and fathers, and romantic anxiety. In addition,
psychological IPA and physical IPA were examined separately, yielding additional
group differences regarding care from father and care from both mother and
father, respectively. This work begins to examine attachment and IPA in new ways
because it examines both parental attachment and romantic attachment in relation
to IPA.
PMID- 28516853
TI - A Gendered Analysis of the Shadow of Sexual Harm Among a College Sample.
AB - This study uses survey methodology to examine correlates of fear of crime among
men and women to discern the unique impact of risk perception, victimization,
vicarious victimization, and fear of sexual harm on fear of crime. Recently,
scholars have begun to examine fear separately by gender, which is vital given
the unique experiences men and women have with fear and victimization. We examine
two different types of fear of crime to determine whether the effects of these
correlates differ by crime type across gender. Results suggest that fear of
sexual harm and risk perception are the most important indicators of fear of
crime for both genders; sexual harm fear is particularly impactful for female
fear of violence. Race and ethnicity also have interesting impacts for male fear
of violent crime because racial and ethnic minorities indicate more fear of
violent crime than White males. The findings illustrate how imperative it is to
continue to examine fear of specific types of crime as well as distinguish fear
by gender.
PMID- 28516854
TI - Mother, Father, and Teacher Agreement on Victimization and Bullying in Children
With Psychiatric Disorders.
AB - Bullying is a significant international problem, and parent-teacher agreement on
identifying perpetrators and victims is poor in general population studies. The
goal of our study is to assess informant discrepancies in children with mental
health disorders. Parents and teachers completed the Pediatric Behavior Scale as
part of a diagnostic evaluation for 1,723 children (ages 2-16 years) referred to
a psychiatry clinic over the past 10 years. Mother and father bullying and
victimization ratings on the Pediatric Behavior Scale were similar, but parent
teacher agreement was poor. Half of parents considered their child a victim,
twice the percentage for teachers. Parents were 1.2 times more likely than
teachers to perceive their child as a bully. Most parents reported their child
was a victim or bully, whereas most teachers reported the children were neither.
For both parents and teachers, victim and bully percentages for our psychiatric
sample were twice as high as in general population studies. Clinicians should
obtain information from multiple informants and consider that teacher report is
likely to be lower than parent report.
PMID- 28516855
TI - Victim Impact Statements: How Victim Social Class Affects Juror Decision Making.
AB - Although the Supreme Court has ruled that victim impact statements (VIS) should
be allowed at trial, the concern voiced in Payne v. Tennessee (1991) and Furman
v. Georgia (1972) was that VIS might enable jurors to make comparative judgments
about the worth of the victim. This study examined the effect VIS and low and
middle socioeconomic status (SES) victims have on jurors' decisions. Mock jurors
listened to 1 of 3 audio recordings of the sentencing phase of a capital murder
trial (no VIS, low SES VIS, or middle SES VIS) and were asked to sentence the
defendant to either life in prison without parole or death. Results indicated VIS
themselves did not significantly affect mock jurors' sentencing decisions.
However, mock jurors who heard the middle SES victim VIS were significantly more
likely to sentence the defendant to death compared to those who heard the low SES
victim VIS. The results suggest that the concerns of the Supreme Court were
valid. Mock jurors were impacted by SES information in the VIS and were more
punitive toward the defendant when he killed a higher rather than a lower SES
person.
PMID- 28516852
TI - Effects of olanexidine gluconate on preoperative skin preparation: an
experimental study in cynomolgus monkeys.
AB - PURPOSE: To determine the bactericidal efficacy of a new topical antiseptic for
preoperative skin preparation, olanexidine gluconate (development code: OPB
2045G), against transient or resident bacterial flora on the skin of cynomolgus
monkeys. METHODOLOGY: After measuring baseline bacterial counts on test sites
marked on the abdomens, we applied olanexidine, chlorhexidine or povidone-iodine.
After 10 min (fast-acting effect) and 6 h (long-lasting effect), bacterial counts
were measured again and log10 reductions were calculated. In addition, we
determined the bactericidal effects on the skin contaminated with blood before or
after applying the antiseptics. RESULTS: In the non-blood-contaminated condition,
the mean log10 reductions of olanexidine at doses of 1-2 % were significantly
higher than those of saline (negative control), but did not significantly differ
from those of 0.5 % chlorhexidine and 10 % povidone-iodine at either time point.
But olanexidine was significantly more effective at both time points than
chlorhexidine and povidone-iodine when applied after the site was contaminated
with blood. Olanexidine was also significantly more effective than chlorhexidine
and as effective as or more effective than povidone-iodine at both time points
when skin was contaminated with blood after the antiseptics were applied.
CONCLUSION: The bactericidal effects of olanexidine were comparable to those of
commercial antiseptics such as chlorhexidine and povidone-iodine in non-blood
contaminated conditions. More importantly, the effect of olanexidine was hardly
affected by blood unlike commercial antiseptics. Thus, it is considered that
olanexidine has a favourable property for skin preparation in various types of
surgical treatments.
PMID- 28516856
TI - Dating Violence Perpetration: Associations With Early Maladaptive Schemas.
AB - Violence between dating couples is a serious and prevalent problem among college
students (Shorey, Cornelius, & Bell, 2008). Social-cognitive theories of
aggression (e.g., Berkowitz, 1990) propose that perpetrators may have more
maladaptive cognitive schemas that increase risk for aggression than non
perpetrators. Thus, this study examined differences between perpetrators and non
perpetrators of dating violence on early maladaptive schemas, which are rigidly
held cognitive and behavioral patterns that guide how individuals encode and
respond to stimuli in their environments (Young, Klosko, & Weishaar, 2003).
Within a sample of female (n = 242) and male (n = 193) college students, results
demonstrated that many early maladaptive schema domains were associated with
psychological and physical dating violence perpetration, although mostly for
women. In addition, the schema domain of impaired autonomy showed medium-to-large
differences between female perpetrators and non-perpetrators, whereas the domain
of impaired limits showed a medium-to-large difference for male perpetrators and
non-perpetrators of physical aggression. These findings add to a growing body of
literature on risk factors for dating violence, suggesting that early maladaptive
schemas may be associated with individual differences in aggression risk. The
results also further support social-cognitive models of aggressive behavior.
PMID- 28516857
TI - Co-Occurring Cyberbullying and School Bullying Victimization and Associations
With Mental Health Problems Among Canadian Middle and High School Students.
AB - This study examined the associations between co-occurring cyberbullying and
school bullying victimization with poor self-rated mental health, psychological
distress, and suicidal ideation and attempts among 4,886 Canadian students in
Grades 7-12 and tested whether these associations differed between middle and
high school students. There are 12.2% of students who were victims of both
cyberbullying and school bullying. After adjusting for covariates, victims of
both cyberbullying and school bullying presented the highest odds of poor self
rated mental health (odds ratio [OR] = 5.02; 95% CI [3.75, 6.74]), psychological
distress (OR = 5.91; 95% CI [4.38, 7.96]), and suicidal ideation (OR = 6.17; 95%
CI [4.44, 8.56]) and attempts (OR = 7.68; 95% CI [3.95, 14.93]). These
associations were stronger among middle-school youth than their high school
counterparts. Results suggest that victims of both cyberbullying and school
bullying may constitute the most vulnerable group and that there is a need for
intervention programs addressing both forms of bullying simultaneously,
particularly among middle school students.
PMID- 28516858
TI - Southern Women at Risk: Narratives of Familial and Social HIV Risk in Justice
Involved U.S. Women in Alabama.
AB - Justice-involved HIV-positive women, particularly those in the U.S. South, are a
hidden, understudied population. Little work has explored their psychosocial
histories in relation to their HIV risk. We conducted a content analysis of their
life history narratives from childhood to present, via in-depth interviews with
24 such women in 2 Alabama cities. Findings included the following: (a) In
childhood/adolescence, consistent HIV risk factors were present, beginning with
early sexual abuse and induction into alcohol/substance use; (b) By early
adulthood, HIV and incarceration risks were compounded in social settings,
through cyclical substance use, revictimization, and reoffending;
PMID- 28516859
TI - Recombinant esterase from Corynebacterium pseudotuberculosis in DNA and subunit
recombinant vaccines partially protects mice against challenge.
AB - PURPOSE: We tested the efficacy of the esterase encoded by cp1002_RS09720 from
Corynebacteriumpseudotuberculosis in recombinant subunit and DNA caseous
lymphadenitis (CLA) vaccines. This target was predicted as one of the best CLA
vaccine candidates by mature epitope density analysis. METHODOLOGY: Gene
cp1002_RS09720 was cloned into two different vectors (pAE for subunit vaccine and
pTARGET for DNA vaccine). Four groups of 15 mice each were immunized with the
recombinant esterase rCP09720 associated with aluminium hydroxide adjuvant (G1),
pTARGET/cp09720 DNA vaccine (G2), a naked pTARGET (G3) or PBS as a negative
control (G4). Immunization occurred in two doses intercalated by a 21 day
interval. Twenty-one days after the last dose administration, animals were
challenged with a virulent C. pseudotuberculosis MIC-6 strain. RESULTS: G1 showed
high levels of IgG1 and IgG2a on days 21 and 42 post-immunization and a
significant level of IFN-gamma (P<0.05), suggesting a Th1 response. The
protection levels obtained were 58.3 and 16.6 % for G1 and G2, respectively.
CONCLUSION: The subunit vaccine composed of the recombinant esterase rCP09720 and
Al(OH)3 is a promising antigenic formulation for use against CLA.
PMID- 28516860
TI - Salmonella DIVA vaccine reduces disease, colonization and shedding due to
virulent S. Typhimurium infection in swine.
AB - PURPOSE: Non-host-adapted Salmonella serovars, including the common human food
borne pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), are
opportunistic pathogens that can colonize food-producing animals without causing
overt disease. Interventions against Salmonella are needed to enhance food
safety, protect animal health and allow the differentiation of infected from
vaccinated animals (DIVA). METHODOLOGY: An attenuated S. Typhimurium DIVA vaccine
(BBS 866) was characterized for the protection of pigs following challenge with
virulent S. Typhimurium. The porcine transcriptional response to BBS 866
vaccination was evaluated. RNA-Seq analysis was used to compare gene expression
between BBS 866 and its parent; phenotypic assays were performed to confirm
transcriptional differences observed between the strains. RESULTS: Vaccination
significantly reduced fever and interferon-gamma (IFNgamma) levels in swine
challenged with virulent S. Typhimurium compared to mock-vaccinated pigs.
Salmonella faecal shedding and gastrointestinal tissue colonization were
significantly lower in vaccinated swine. RNA-Seq analysis comparing BBS 866 to
its parental S. Typhimurium strain demonstrated reduced expression of the genes
involved in cellular invasion and bacterial motility; decreased invasion of
porcine-derived IPEC-J2 cells and swimming motility for the vaccine strain was
consistent with the RNA-Seq analysis. Numerous membrane proteins were
differentially expressed, which was an anticipated gene expression pattern due to
the targeted deletion of several regulatory genes in the vaccine strain. RNA-Seq
analysis indicated that genes involved in the porcine immune and inflammatory
response were differentially regulated at 2 days post-vaccination compared to pre
vaccination. CONCLUSION: Evaluation of the S. Typhimurium DIVA vaccine indicates
that vaccination will provide both swine health and food safety benefits.
PMID- 28516861
TI - Victim Gender, Rater Attitudes, and Rater Violence History Influence Perceptions
of Intimate Partner Violence.
AB - Perceptions of intimate partner violence (IPV) have been proposed to play a role
in the stigmatization and underreporting of violence by individuals who are
victimized by intimate partners, especially in cases that are inconsistent with
the male-to-female IPV paradigm. We examined the independent and combined
influences of victim and perpetrator sex, attitudes toward gender roles, and
history of IPV perpetration on perceptions of IPV among 240 college students. We
employed a vignette methodology to manipulate perpetrator and victim sex in a
fully crossed design. Results indicate that violence perpetrated against males is
perceived as less serious and more justified, and male victims are perceived to
be more blameworthy than female victims. Traditional gender role attitudes and
histories of IPV perpetration are associated with greater blaming of victims and
justification of perpetrators across contexts.
PMID- 28516863
TI - Sporadic Creutzfeldt-Jakob Disease in 2 Plasma Product Recipients, United
Kingdom.
AB - Sporadic Creutzfeldt-Jakob disease (sCJD) has not been previously reported in
patients with clotting disorders treated with fractionated plasma products. We
report 2 cases of sCJD identified in the United Kingdom in patients with a
history of extended treatment for clotting disorders; 1 patient had hemophilia B
and the other von Willebrand disease. Both patients had been informed previously
that they were at increased risk for variant CJD because of past treatment with
fractionated plasma products sourced in the United Kingdom. However, both cases
had clinical and investigative features suggestive of sCJD. This diagnosis was
confirmed in both cases on neuropathologic and biochemical analysis of the brain.
A causal link between the treatment with plasma products and the development of
sCJD has not been established, and the occurrence of these cases may simply
reflect a chance event in the context of systematic surveillance for CJD in large
populations.
PMID- 28516862
TI - Non-essential MCM-related proteins mediate a response to DNA damage in the
archaeon Methanococcus maripaludis.
AB - The single minichromosome maintenance (MCM) protein found in most archaea has
been widely studied as a simplified model for the MCM complex that forms the
catalytic core of the eukaryotic replicative helicase. Organisms of the order
Methanococcales are unusual in possessing multiple MCM homologues. The
Methanococcus maripaludis S2 genome encodes four MCM homologues, McmA-McmD. DNA
helicase assays reveal that the unwinding activity of the three MCM-like proteins
is highly variable despite sequence similarities and suggests additional motifs
that influence MCM function are yet to be identified. While the gene encoding
McmA could not be deleted, strains harbouring individual deletions of genes
encoding each of the other MCMs display phenotypes consistent with these proteins
modulating DNA damage responses. M. maripaludis S2 is the first archaeon in which
MCM proteins have been shown to influence the DNA damage response.
PMID- 28516864
TI - Genomic Analysis of Salmonella enterica Serovar Typhimurium DT160 Associated with
a 14-Year Outbreak, New Zealand, 1998-2012.
AB - During 1998-2012, an extended outbreak of Salmonella enterica serovar Typhimurium
definitive type 160 (DT160) affected >3,000 humans and killed wild birds in New
Zealand. However, the relationship between DT160 within these 2 host groups and
the origin of the outbreak are unknown. Whole-genome sequencing was used to
compare 109 Salmonella Typhimurium DT160 isolates from sources throughout New
Zealand. We provide evidence that DT160 was introduced into New Zealand around
1997 and rapidly propagated throughout the country, becoming more genetically
diverse over time. The genetic heterogeneity was evenly distributed across
multiple predicted functional protein groups, and we found no evidence of host
group differentiation between isolates collected from human, poultry, bovid, and
wild bird sources, indicating ongoing transmission between these host groups. Our
findings demonstrate how a comparative genomic approach can be used to gain
insight into outbreaks, disease transmission, and the evolution of a multihost
pathogen after a probable point-source introduction.
PMID- 28516865
TI - Hospital Outbreaks of Middle East Respiratory Syndrome, Daejeon, South Korea,
2015.
AB - From May through July 2015, a total of 26 cases of Middle East Respiratory
Syndrome were reported from 2 hospitals in Daejeon, South Korea, including 1
index case and 25 new cases. We examined the epidemiologic features of these
cases and found an estimated median incubation period of 6.1 days (8.8 days in
hospital A and 4.6 days in hospital B). The overall attack rate was 3.7% (4.7% in
hospital A and 3.0% in hospital B), and the attack rates among inpatients and
caregivers in the same ward were 12.3% and 22.5%, respectively. The overall case
fatality rate was 44.0% (28.6% in hospital A and 63.6% in hospital B). The use of
cohort quarantine may have played a role in preventing community spread, but
additional transmission occurred among members of the hospital cohort quarantined
together. Caregivers may have contributed in part to the transmission.
PMID- 28516866
TI - Invasive Serotype 35B Pneumococci Including an Expanding Serotype Switch Lineage,
United States, 2015-2016.
AB - We used whole-genome sequencing to characterize 199 nonvaccine serotype 35B
pneumococcal strains that caused invasive pneumococcal disease (IPD) in the
United States during 2015-2016 and related these findings to previous serotype
35B IPD data obtained by Active Bacterial Core surveillance. Penicillin
nonsusceptible 35B IPD increased during post-pneumococcal 7-valent conjugate
vaccine years (2001-2009) and increased further after implementation of
pneumococcal 13-valent conjugate vaccine in 2010. This increase was caused
primarily by the 35B/sequence type (ST) 558 lineage. 35B/ST558 and vaccine
serotype 9V/ST156 lineages were implicated as cps35B donor and recipient,
respectively, for a single capsular switch event that generated emergent
35B/ST156 progeny in 6 states during 2015-2016. Three additional capsular switch
35B variants were identified, 2 of which also involved 35B/ST558 as cps35B donor.
Spread of 35B/ST156 is of concern in view of past global predominance of
pathogenic ST156 vaccine serotype strains. Protection against serotype 35B should
be considered in next-generation pneumococcal vaccines.
PMID- 28516867
TI - The link between Proteus mirabilis, environmental factors and autoantibodies in
rheumatoid arthritis.
AB - Rheumatoid arthritis (RA) is a relatively common and potentially disabling immune
mediated inflammatory systemic disease, predominantly affecting women and
characterised by multiple small joint arthritis. Extensive data supports the
roles of genetic, environmental and microbial factors in the triggering and
development of this disease. Proteus mirabilis is considered as the main
microbial culprit in the causation of RA. The evidence for the role of these
microbes in RA and their links with commonly associated autoantibodies such as
rheumatoid factors and anti-citrullinated peptide antibodies have been elucidated
together with their relations with some of the non-microbial environmental
factors which have been implicated in the aetiopathogenesis of RA. The most
likely mechanism in the development of RA is "molecular mimicry" where Proteus
antigens were found to share homologous sequences, which cross-react with certain
self-antigens present in synovial tissues. This could raise possibilities for
implementing a new therapeutic strategy in the treatment of RA.
PMID- 28516868
TI - Predicting responses in patients with rheumatoid arthritis to disease-modifying
agents using baseline clinical data.
AB - OBJECTIVES: The optimal treatment for active rheumatoid arthritis (RA) is
unresolved, particularly in early RA. We used data from an observational cohort
to develop the simple predictor algorithm and evaluated its application in two
completed clinical trials in early and established RA. We assessed whether using
a simple algorithm can identify patients who have persisting active disease
despite treatment with disease-modifying drugs (DMARDs). We also examined if
patients who have lower likelihoods of persisting active RA are likely to benefit
from intensive treatment. METHODS: We developed a simple predictive score for
persisting disease activity using conventional clinical assessments in an
observational cohort of patients with early RA (ERAN). It was tested in two
trials in early (CARDERA) and established (TACIT) RA. Persistent disease activity
was defined as disease activity score for 28 joints (DAS28) >3.2 at both 6 and 12
months. RESULTS: Regression modelling identified three main predictors of
persisting active disease in ERAN; tender joint counts, health assessment
questionnaire (HAQ) scores and ESR. We dichotomised these predictors (>=6 tender
joint counts, >=1.0 HAQ >=20 mm/h ESR) in a four-point prediction score. This
simple prediction score predicted persisting active disease in the ERAN cohort
and both CARDERA and TACIT trials. Patients with high scores were more likely to
have persistently active disease at 6 and 12 months. The relationship was weaker
in TACIT because no patients were without any predictive factors. CONCLUSIONS:
Combining tender joint counts, ESR and HAQ in a simple predictive score
prospectively identifies patients with higher risks of persistent disease
activity over the next 12 months. More patients with all three risk factors had
persistent active disease than those with none or one risk factor.
PMID- 28516869
TI - Recommendations for infectious disease screening in migrants to Western Europe
with inflammatory arthropathies before starting biologic agents. Results from a
multidisciplinary task force of four European societies (SIR, SER, SIMET, SEMTSI)
facing the largest impact of the flow of migrants today.
AB - OBJECTIVES: Inflammatory arthritis needs infectious disease screening before
starting a biologic agent, however, few data are known about migrant patients,
who represent a peculiar population which requires a multidisciplinary approach
among international health specialists and should also be considered by health
authorities. For this reason, the Italian and Spanish Societies of Rheumatology
(SIR and SER) and Tropical Medicine (SIMET and SEMTSI) promoted a
multidisciplinary task force in order to produce specific recommendations about
screening and advices to be considered in migrant patients with inflammatory
arthritis candidate to receive biological therapy, according to their
geographical origin. METHODS: The experts provided a prioritised list of research
questions and the eligible spectrum of inflammatory arthritis, biologic drugs and
infectious disease were defined in order to perform a systematic literature
review. A search was made in Medline, Embase and Cochrane library, updated to
March 2015. Ubiquitous infections and HBV, HCV, HIV and tuberculosis that are
already considered in national and international recommendations, were not
included. The strength of each recommendation was determined. RESULTS: The task
force members agreed on 7 overarching principles. The risk of reactivation of
selected potentially latent infectious disease was addressed in migrants with
inflammatory arthritis candidates for biologics was considered and 15 potentially
relevant infections were identified. CONCLUSIONS: Fifteen disease-specific
recommendations were formulated on the basis of high level of agreement among the
experts panel.
PMID- 28516870
TI - The relevance of cluster analyses to stratify systemic lupus erythematosus:
increased mortality with heavier treatment.
PMID- 28516871
TI - Diagnosis of catastrophic anti-phospholipid syndrome in a patient tested negative
for conventional tests.
AB - Catastrophic antiphospholipid syndrome (CAPS) is a severe variant of APS,
characterised by clinical evidence of multiple organ involvement developing over
a very short period of time, histopathological evidence of multiple small vessel
occlusions and laboratory confirmation of the presence of aPL (lupus
anticoagulant and/or anticardiolipin antibodies and/or anti-Beta2-glcyoprotein I
antibodies). Here we report a case of a 39-year-old woman patient who developed a
CAPS which was negative to the conventional aPL but positive for aPL in thin
layer chromatography immunostaining and vimentin/cardiolipin antibodies by ELISA
test. The patient was treated with high doses of glucocorticoids, intravenous
immunoglobulins plasma exchange and immunoadsorbent apheresis with a significant
improvement of the ischaemic lesions of the hands even though the necrosis of the
feet progressively worsened. As a result, the patient underwent partial surgical
amputation of the feet. To our knowledge, this is the first ever reported case of
CAPS diagnosed by means of thin layer chromatography immunostaining and
vimentin/cardiolipin antibody ELISA test.
PMID- 28516872
TI - Glucocorticoid-sparing effect of first-year anti-TNFalpha treatment in rheumatoid
arthritis (CORPUS Cohort).
AB - OBJECTIVES: Anti-TNFalpha agents are indicated in selected patients with
rheumatoid arthritis (RA) who respond inadequately to methotrexate and
particularly when glucocorticoids are mandatory. We evaluated whether a
glucocorticoid-sparing effect occurred during the first year of anti-TNF-alpha
therapy. METHODS: Between 2007 and 2009, the French multicentre, longitudinal,
prospective, observational, population-based CORPUS cohort included biologic
naive patients with inflammatory joint disease. Patients with active RA treated
with glucocorticoids were included. Patients who received at least one anti
TNFalpha injection during follow-up were compared to anti-TNF-alpha non-users.
RESULTS: Among the 205 patients, 76.1% were women, mean disease duration was
7.7+/-8.3 years, mean DAS28 was 5.2+/-1.3, mean follow-up was 13.1+/-2.8 months,
and mean prednisone dose was 9.9+/-9.6 mg/day. The 75 (36.6%) anti-TNF-alpha
recipients were younger, had a longer RA duration, more often tested positive for
rheumatoid factor and anti-citrullinated peptide antibody, more often received
previous DMARDs, received a higher methotrexate dosage, had fewer intra-articular
glucocorticoid injections at baseline and were more often followed by hospital
practitioners than non-recipients. Mean prednisone dosage decreased from 11.8+/
12.7 to 5.9+/-9.7 mg/day in recipients and from 8.7+/-7.1 to 5.0+/-4.4 mg/day in
non-recipients. Prednisone was stopped more often among recipients (21/59, 35.6%)
than among non-recipients (16/94, 17.0%) (p=0.01). By multivariate analysis,
factors independently associated with lower prednisone requirements were baseline
daily prednisone dosage, a CRP >10 mg/l and not to be followed by an office-based
practitioner. CONCLUSIONS: This study showed a significantly higher
glucocorticoid discontinuation rate among anti-TNF-alpha recipients than among
non-recipients. However, the glucocorticoid-sparing effect was small and not
observed by multivariate analysis.
PMID- 28516873
TI - About the AIRTRIP randomised clinical trial: comments on the article by Brucato
et al.
PMID- 28516875
TI - Reply to: Moyamoya disease and systemic sclerosis (MoSys syndrome): a combination
of two rare entities: comment to the authors.
PMID- 28516874
TI - Long-term effects of interleukin-17A inhibition with secukinumab in active
ankylosing spondylitis: 3-year efficacy and safety results from an extension of
the Phase 3 MEASURE 1 trial.
AB - OBJECTIVES: Secukinumab, a fully human anti-IL-17A monoclonal antibody, provided
rapid and sustained improvements in signs and symptoms of ankylosing spondylitis
(AS) over 2 years in the Phase 3 MEASURE 1 trial. Here, we report efficacy and
safety after 3 years of treatment. METHODS: AS subjects completing 2 years of
treatment every 4 weeks with subcutaneous secukinumab 150 or 75 mg (following
intravenous loading or initial placebo treatment to 16/24 weeks) entered a
separate 3-year extension study (NCT01863732). Assessments included ASAS20/40,
ASAS5/6, BASDAI, BASDAI 50, BASFI, BASMI, SF-36 physical component summary, ASAS
partial remission and ASDAS-CRP. Results were also analysed by prior anti-TNF
treatment status. RESULTS: Among 290 subjects completing the core trial, 274
entered the extension study, with 260 subjects (94.9%) completing 156 weeks of
treatment. ASAS20/40 response (observed) was 80.2%/61.6% in the IV->150 mg group
and 75.5%/50.0% in the IV->75 mg group after 156 weeks. Sustained improvements
were also seen in BASDAI, BASFI, BASMI and across all other endpoints regardless
of previous exposure to anti-TNF agents. Mean secukinumab exposure was 964.3 days
(137.8 weeks). Discontinuation rates were low, and secukinumab had a favourable
safety profile, consistent with previous reports. Exposure-adjusted incidence
rates for serious infections, Candida infections, Crohn's disease, ulcerative
colitis, malignant/unspecified tumours, and adjudicated major adverse cardiac
events were 1.1, 0.4, 0.5, 0.1, 0.5 and 0.7 per 100 subject-years, respectively.
CONCLUSIONS: Secukinumab provided sustained efficacy in signs, symptoms and
physical function in subjects with AS over 3 years. No new safety signals were
observed.
PMID- 28516876
TI - Multiple testing in the 'Canakinumab in atherosclerosis' trial: correction
required?
PMID- 28516877
TI - Validity of the Workers Productivity and Activity Impairment Questionnaire:
Specific Health Problem (WPAI:SHP) in patients with systemic sclerosis.
AB - OBJECTIVES: To evaluate the construct validity of the Workers Productivity and
Impairment Activity Index: Specific Health Problem (WPAI:SHP) in Australian
systemic sclerosis (SSc) patients. METHODS: SSc patients, identified through the
Australian Scleroderma Cohort Study database, completed the WPAI:SHP and a
quality of life instrument (PROMIS-29) cross-sectionally. The construct validity
of the WPAI:SHP was assessed by the correlations between the WPAI:SHP and a range
of SSc health states. Non-parametric correlation, including Spearman's
correlation (rho), was used to test the validity of WPAI:SHP and ability to
distinguish between different health states. RESULTS: A total of 476 completed
questionnaires was returned, equating to a response rate of 63.7%. Among those
under 65 years of age, 155 patients (55.2%) were in paid employment. Employed
patients had a mean (+/- SD) age of 56.5 (9.8) years and were predominantly
female (87.3%) with limited disease subtype (75.6%). The WPAI:SHP showed
construct validity based on moderate to strong correlations with health status as
assessed by a range of health outcome measures including disease activity
(rho=0.34-0.39, p=0.001), physical function (rho=0.55-0.62, p=0.001), disease
severity(rho=0.55-0.62, p=0.001), fatigue (rho= 0.62-0.63, p=0.001), pain
(rho=0.68-0.71, p=0.001), and breathlessness (rho=0.39-0.46, p=0.001).
Furthermore, according to the effect size, the WPAI:SHP scores have a large
discriminative ability (d=1.26-1.47) for distinguishing SSc patients with
different health outcomes. CONCLUSIONS: The WPAI is a valid questionnaire for
assessing impairments in paid employment and social activities in SSc patients,
and for measuring the relative differences between SSc patients with varying
health states.
PMID- 28516878
TI - High incidence of vertebral osteoporotic fracture within the first year after
liver transplantation.
AB - OBJECTIVES: Bone loss is a complication for patients with liver diseases and
after transplantation, which results in increased fracture risk. The aim of this
study was to determine the incidence of osteoporotic vertebral fractures
following liver transplantation. METHODS: We performed a prospective study of
patients who were awaiting liver transplantation. Patients were seen at baseline
(visit 1) and one year after transplantation (visit 2). At each visit, risk
factors of osteoporosis were collected, biochemical tests were performed and bone
mineral density with Vertebral Fracture Assessment was assessed. RESULTS: One
hundred and fifteen patients were in the pre-transplant group and 33 patients
were in the post-transplant group. In the pre-transplant group, the prevalence of
vertebral fractures was 23.5%. The prevalence of densitometric osteoporosis was
higher at the lumbar spine than at the femoral neck. In the post-transplant
group, the prevalence of vertebral fractures at visit 1 and visit 2 was 33.3% and
60.6% respectively with an incidence of 23.1 fractures per 100 patient-years.
CONCLUSIONS: Bone fragility was highly prevalent before transplantation and
worsens one year after transplantation. Bone status should be evaluated in
patients with liver diseases before transplantation to identify patients at high
risk of fracture and help clinicians to prescribe appropriate preventive care.
PMID- 28516879
TI - Comparison of efficacy of first- versus second-line adalimumab in patients with
rheumatoid arthritis: experience of the Italian biologics registries.
AB - OBJECTIVES: Targeted drugs against key pathogenetic molecules such as TNF-alpha
have significantly improved outcomes in rheumatoid arthritis (RA). They are
widely used in clinical practice and drug registries give us information to
support their use. Adalimumab (ADA) is able to induce a comprehensive disease
control in RA by achieving clinical, functional and radiographic control.
METHODS: By interrogating 2 Italian registries, LORHEN and GISEA, we analysed the
efficacy of ADA in first- or second-line in a total of 2262 RA patients. RESULTS:
Patients in 1st line were significantly older, with lower disease activity and
HAQ scores compared to 2nd line. In 1st line, rates of DAS28-remission (DAS28rem)
at 2 years were 34.4% while 26.5% in 2nd line (p=0.038). A normal HAQ score
(HAQ<=0.5) was achieved in 53.5% after 2 years in 1st line versus 30.1% in 2nd
(p<0.0001). DAS28rem+HAQ<=0.5, a combined parameter that we defined global
clinical disease control, was reached in 20.7% in 1st line versus 13.3% in 2nd
(p<0.01). Five-year-survival on therapy was higher for patients in 1st line
(45.6% vs. 33.2%, p<0.0001). Discontinuation due to lack of efficacy was lower in
1st line (37.4 vs. 54.4%, p<0.0001). Rates of adverse events were similar.
CONCLUSIONS: Responses in 1st line are generally significantly better than after
a first anti-TNF-alpha failure but patients in 2nd line have a worse clinical and
functional profile. A global disease control with clinical and functional
remission is an achievable target in both lines.
PMID- 28516880
TI - Abatacept therapy reduces CD28+CXCR5+ follicular helper-like T cells in patients
with rheumatoid arthritis.
AB - OBJECTIVES: The characteristics of T cells targeted by abatacept (ABT) in cases
of rheumatoid arthritis (RA) are still unknown. The goal of the study was to
determine the pathogenicity of T cells and the predictors of therapeutic effects
of ABT. METHODS: We analysed the peripheral T cell phenotype of 34 RA patients
via flow cytometry. The correlation of the phenotypes of CD4+ T cells with
clinical disease activity and change in CD4+ T cell subsets at baseline and 24
weeks after ABT treatment were evaluated. RESULTS: RA patients showed an increase
in the proportion of CD28- cells among CD4+ cells, which was significantly high
in patients who had not achieved remission after ABT therapy. The proportions of
CD4+CXCR5+ T follicular helper-like (Tfh-like) cells increased in RA patients
compared to healthy donors. The proportions of Tfh-like cells among CD4+CD28+
cells were significantly higher than those among CD4+CD28- cells. The proportion
of Tfh-like cells was higher in anti-cyclic citrullinated peptide antibody (ACPA)
positive patients. By contrast, the proportions of CD4+CXCR3+ T helper 1-like
(Th1-like) cells and effector memory phase T cells among CD4+CD28- cells were
significantly higher than those among CD4+CD28+ cells, and the proportion of
these cells did not correlate with disease activity. After ABT therapy, the
proportion of Tfh-like cells among CD4+CD28+ cells was significantly reduced.
CONCLUSIONS: These results imply that CD4+ CD28+ Tfh-like cells could possibly be
the targets of ABT. Conversely, CD4+ CD28- cells may be a potential predictor of
treatment resistance.
PMID- 28516882
TI - Interstitial lung disease is associated to infections of lower respiratory tract
in immunocompromised rheumatoid arthritis patients.
PMID- 28516881
TI - Exploring the remission concept in rheumatoid arthritis with patients and
rheumatologists: time for a new approach?
AB - OBJECTIVES: To explore the remission concept in rheumatoid arthritis (RA) and to
compare remission definitions and related concepts between rheumatologists and
patients with the purpose of identifying similarities and disparities to
comprehend the different perspectives of the disease. METHODS: This was a
qualitative study of discourse and content analysis through focus groups,
conducted from February to March 2016. Four focus groups were set up, each one
with different interests: rheumatologists involved in basic research (BR),
rheumatologists with high specialisation in imaging techniques (IR), clinical
rheumatologists (CR), and patients (PA). RESULTS: There is no consensus in a
remission definition in RA; differences exist between-groups, rheumatologists and
patients value remission differently, and there are discrepancies within the
group of rheumatologists. Rheumatologists highlight quantifiable objective
parameters, in contrast, patients did not consider objective measures as the best
instruments, and they prefer subjective measures of remission. The data confirmed
the existence of two sources of knowledge of the disease, technical (physicians)
and experiential (patients). These sources of knowledge should concur in order to
establish new remission criteria well-adjusted to reality. CONCLUSIONS: The lack
of consensus between key groups implicated in defining remission and remission
criteria suggests a new strategy for its operational definition. Our group
proposes that subjects with a balance between experiential and technical
knowledge, should be the ones in charge of this assignment.
PMID- 28516883
TI - Sarcoidosis and tocilizumab: is there a link?
PMID- 28516885
TI - RAPID3 correlates with ESSPRI and other patient-reported outcomes in patients
with primary Sjogren's syndrome.
PMID- 28516884
TI - Patient participation in patient-reported outcome instrument development in
systemic sclerosis.
AB - OBJECTIVES: The patient perspective captured using Patient-Reported Outcome (PRO)
instruments provide insight into the patient condition not always captured by
physician-derived assessment tools. Target patient population involvement is an
essential component of PRO instrument development. We have reviewed the level of
patient involvement in the development of PRO instruments used in the assessment
of systemic sclerosis (SSc). METHODS: A comprehensive literature review was
undertaken to identify studies reporting PRO instruments in SSc. Studies were
assessed to establish whether the PRO instruments had been developed specifically
for SSc or adopted from other disease areas. Studies reporting PRO instruments
specific for SSc were scrutinised for evidence of target patient population
involvement in the development of the instrument. RESULTS: A total of 58 PRO
instruments that have been used in SSc research were identified. Twelve (21%) of
these were developed specifically for outcome assessment within SSc populations.
Of these, 5 (42%) had not reported any patient involvement in the development
phase of the instrument. Five SSc PRO instruments (42%) involved target patient
population in the domain/item generation stage. Four (33%) of SSc PRO instruments
had undertaken cognitive interviewing to ensure item wording adequately captured
the intended conceptual framework. CONCLUSIONS: The majority of PRO instruments
used to assess SSc have not involved significant target patient involvement in
their development. By involving patients in the development of novel PRO
instruments in SSc, we can ensure such instruments adequately capture the
experiences most relevant to our patients.
PMID- 28516886
TI - Patterns of tocilizumab use, effectiveness and safety in patients with rheumatoid
arthritis: core data results from a set of multinational observational studies.
AB - OBJECTIVES: To observe patients with rheumatoid arthritis (RA) treated with the
interleukin-6 receptor-alpha inhibitor tocilizumab (TCZ) in routine clinical
practice. METHODS: Data on concomitant medications, effectiveness and safety were
pooled from independent, multinational studies in patients with RA initiating
intravenous TCZ according to local label recommendations observed in routine
practice for 6 months. Patients were grouped by TCZ monotherapy or combination
therapy with conventional synthetic disease-modifying anti-rheumatic drugs
(csDMARDs). The primary endpoint was the proportion of patients receiving TCZ
after 6 months. RESULTS: Of 1336 patients enrolled, 506 (37.9%) received TCZ
monotherapy and 830 (62.1%) received combination therapy. Kaplan-Meier analysis
estimated that 80% (95% CI, 76%-83%) of monotherapy and 87% (95% CI, 84%-89%) of
combination therapy patients continued to receive TCZ at 6 months (log-rank
p<0.001). During the observation period, TCZ was discontinued by 113 (22.3%)
monotherapy patients and 116 (14.0%) patients on combination therapy. The mean
prednisone-equivalent oral corticosteroid dose was 8.4 mg/day for monotherapy and
combination therapy patients at baseline and 7.7 and 7.6 mg/day, respectively, at
month 6. Adverse events or laboratory abnormalities requiring TCZ dose
modification were reported for 66 (13.0%) monotherapy and 130 (15.7%) combination
therapy patients. Effectiveness at 6 months was similar between groups; mean (SD)
change from baseline in Clinical Disease Activity Index (CDAI) was -20.3 (14.18)
for monotherapy and -22.3 (16.09) for combination therapy (p=0.7347).
CONCLUSIONS: In routine clinical practice, 38% of patients received TCZ as
monotherapy. Persistence on monotherapy or in combination therapy with csDMARDs
was high, with a slight trend towards a higher rate with combination therapy, and
effectiveness was similar between groups.
PMID- 28516888
TI - One biopsy, two diagnoses: statin-induced autoimmune myopathy in combination with
extranodal marginal zone lymphoma.
PMID- 28516887
TI - Tenosynovitis in rheumatoid arthritis patients on biologic treatment: involvement
and sensitivity to change compared to joint inflammation.
AB - OBJECTIVES: Extensor carpi ulnaris (ECU) and tibialis posterior (TP) tendons are
often involved in RA and the present aim was to examine by ultrasound (US) their
frequency of inflammation and sensitivity to change in comparison to joint
involvement as well as clinical examinations. METHODS: US, clinical and
laboratory assessments were performed when starting biologic DMARD (bDMARD) and
after 1, 2, 3, 6 and 12 months including bilateral grey-scale (GS) and power
Doppler (PD) semi-quantitatively (0-3) scoring of ECU and TP tendons and 18
joints. Changes from baseline to follow-up were explored by Wilcoxon signed rank
test, associations by Spearman's rank correlations and responses to treatment by
Standardised Response Means (SRMs). RESULTS: 157 patients (mean age/disease
duration 52.4/10.2 years) were included. ECU/TP tenosynovitis was frequent
(baseline GS/PD pathology in 76/50% of patients) and more prevalent than
synovitis of large joints. Tenosynovitis sum scores decreased throughout follow
up (p<0.001) and was correlated with US of joints (0.51-0.62), clinical
assessments (swollen joint count (0.29-0.41) and assessor's global (0.35-0.46))
(p<0.001). US tenosynovitis sum scores had SRMs comparable to joint, clinical and
laboratory assessments. CONCLUSIONS: Tenosynovitis in ECU/TP tendons were
frequent, sensitive to change during bDMARD treatment and were associated to
joint and clinical assessments. This supports the argument for tenosynovitis to
be included in US scores of RA patients, while further studies should explore
which tendons.
PMID- 28516889
TI - An update on the animal models in hyperuricaemia research.
AB - Hyperuricaemia is a metabolic disease caused by purine metabolic abnormalities,
mainly due to the increased formation or reduced excretion of uric acid. In
recent years, it has been proved that hyperuricaemia is an important risk factor
for chronic kidney disease (CKD) and cardiovascular disease, and it also takes
part in the pathophysiology of metabolic syndrome. In addition, more attention
has been concentrated on the pathogenesis or treatment of hyperuricaemia. Since
establishing an animal model on hyperuricaemia is the foundation for further
researches, several methods to establish the hyperuricaemia model have been
developed. In this article, remarkable progress on the modelling approach are
summarised, and a comparison study on different methods of developing
hyperuricaemia animal models was conducted.
PMID- 28516891
TI - Proposed Bose-Einstein condensation of magnons in nanostructured films of Gd at
low temperature and its manifestations in electrical resistivity and
magnetoresistance.
AB - In this paper we report the observation of a proposed Bose-Einstein condensation
(BEC) of magnons in a temperature range of around 15-20 K in nanostructured films
of Gd with grain sizes that are much larger than the size range where
superparamagentism is expected. The observation was carried out using magnetic as
well as high precision resistivity and magnetoresistance (MR) measurements
performed to low temperatures. We observe that the experimental observations
depend crucially on one parameter, namely softening of the spin wave stiffness
parameter D at BEC and the resistivity as well as MR can be related
quantitatively to magnetic measurements through the temperature variation of the
constant D in the vicinity of the transition. This paper establishes that the BEC
reported before in nanocrystalline Gd can be extended to a somewhat larger size
range.
PMID- 28516890
TI - Tocilizumab in the treatment of patients with rheumatoid arthritis in real
clinical practice: results of an Italian observational study.
AB - OBJECTIVES: To describe the effectiveness and safety of tocilizumab (TCZ), an
interleukin-6 receptor inhibitor, in a cohort of patients with rheumatoid
arthritis (RA) recruited in clinical practice. METHODS: TRUST was an
observational study in RA patients who started treatment with TCZ in the 6 months
prior to site activation and were still on treatment at start of study; patients
were followed up to 12 months after the first TCZ infusion. RESULTS: 322 RA
patients were enrolled in 59 Italian centres (mean age: 55.8 years; mean disease
duration: 120.5 months; baseline DAS28: 5.3). After 6 months of TCZ treatment,
patients achieving low disease activity (DAS28 <=3.2; 57.52%) or disease
remission (DAS28 <2.6; 38.05%) were 216 out of 226 patients with available DAS28
(p<0.001). No statistically significant differences were found in mean DAS28 and
HAQ score changes from baseline (start of TCZ treatment) to study end between
patients previously inadequately responding to disease-modifyinganti-rheumatic
drugs (DMARD-IR) or to DMARDs plus tumour necrosis factor inhibitors (DMARD +TNFi
IR): both patient populations responded to TCZ. A statistically significant
decrease in mean VAS Fatigue score (48.4 vs. 34.7; p=0.0025) at month 6 was
observed. In patients treated with TCZ as monotherapy (32.61%), DAS28, VAS
fatigue and HAQ scores decreased from baseline to any post-baseline time point.
Overall, 62 patients (19.3%) prematurely discontinued TCZ treatment, 24 (7.5%)
for safety reasons. Drug-related adverse events occurred in 92 patients (28.6%)
(mostly 3 hypercholesterolaemia and leucopenia) and drug-related serious adverse
events in 11 patients (3.4%). CONCLUSIONS: This study confirms the good
effectiveness and safety profile of TCZ in real life RA patient care.
PMID- 28516892
TI - Current situations and discussions in Japan in relation to the new occupational
equivalent dose limit for the lens of the eye.
AB - Since the International Commission on Radiological Protection recommended
reducing the occupational equivalent dose limit for the lens of the eye in 2011,
there have been extensive discussions in various countries. This paper reviews
the current situation in radiation protection of the ocular lens and the
discussions on the potential impact of the new lens dose limit in Japan. Topics
include historical changes to the lens dose limit, the current situation with
occupational lens exposures (e.g., in medical workers, nuclear workers, and
Fukushima nuclear power plant workers) and measurements, and the current status
of biological studies and epidemiological studies on radiation cataracts. Our
focus is on the situation in Japan, but we believe such information sharing will
be useful in many other countries.
PMID- 28516894
TI - Toy model for uncommon spin-orbit-driven spin-torque terms.
AB - A toy model combining the angular magneto electric (AME) coupling Hamitonian
(Mondal et al 2015 Phys. Rev. B 92 100402) with long-range magnetic dipolar
interactions is used to investigate spin-torque phenomena in a magnetic spin
valve. It is found that such model (1) gives rise to spin-torque expressions that
are analogous in form to those of the common spin-transfer torques; but also (2)
predicts additional spin-torque terms, which are generated by an electrical
current oriented along unconventional, in-plane directions. The magnitude of the
AME induced terms is estimated and the conditions under which they may contribute
significantly are explored.
PMID- 28516893
TI - Design of electrohydrodynamic sprayed polyethylene glycol hydrogel microspheres
for cell encapsulation.
AB - Electrohydrodynamic spraying (EHS) has recently gained popularity for
microencapsulation of cells for applications in cell delivery and tissue
engineering. Some of the polymers compatible with EHS are alginate, chitosan, and
other similar natural polymers, which are subject to ionotropic or physical
gelation. It is desirable to further extend the use of the EHS technique beyond
such polymers for wider biofabrication applications. Here, building upon our
previous work of making PEG microspheres via EHS, we utilized the principles of
EHS to fabricate cell-laden polyethylene glycol (PEG) hydrogel microspheres. The
gelation of PEG hydrogel microspheres was achieved by forming covalent crosslinks
between multiarm PEG acrylate and dithiol crosslinkers via Michael-type addition.
We conducted a detailed investigation of the critical parameters of EHS, such as
the applied voltage, inner needle diameter (i.d. needle), and flow rate, to
obtain PEG microspheres with high cell viability and tightly-controlled diameters
in the range of 70-300 MUm. The polydispersity of cell-laden PEG hydrogel
microspheres as measured by % coefficient of variation was between 6% and 23% for
all conditions tested. We established that our method was compatible with
different cell types and that all tested cell types could be encapsulated at high
densities of 106-109 and >=90% encapsulation efficiency. We observed cell
aggregation within the hydrogel microspheres at applied voltage >5 kV. Since PEG
is a synthetic polymer devoid of cell attachment sites, we could overcome this
limitation by tethering Arg-Gly-Asp-Ser (RGDS) peptide to the PEG hydrogel
microspheres; upon RGDS tethering, we observed uniform cell dispersion. The
microencapsulated cells could be cultured in the PEG hydrogel microspheres of
different sizes for up to one week without significant loss in cell viability. In
conclusion, the EHS technique developed here could be used to generate cell-laden
PEG hydrogel microspheres of controlled sizes for potential applications in cell
delivery and organoid cultures.
PMID- 28516895
TI - Effect of magnetic field on electronic transport in a bilayer graphene nanomesh.
AB - We report on the observation of an unexpected sudden increase of resistance in
bilayer graphene nanomesh (GNM) in the temperature range 270 ~ 300 K that is
strongly dependent on the magnetic field strength. We conjecture that the sharp
increase in resistance originates from ripple scattering as induced by substrate
roughness. The observed result is evidence of extrinsic corrugation in bilayer
GNM as an additional scattering source that contributes to significant
resistance. The observed weak localization in the GNM indicates intervalley
scattering induced by lattice defects acts as resonant scatterers attribute to
the high D peak. Magnetotransport measurement strongly supports that the charge
inhomogeneity related to the intrinsic disorder in bilayer GNM and the positive
magnetoresistance shows a linear behavior with magnetic field strength.
Potentially, the observed phenomena, therefore, point to a clear pathway towards
practical application of bilayer GNM and to the design of a graphene magnetic
sensor that can be manipulated by a magnetic field and a new generation of
spintronics.
PMID- 28516896
TI - Direct and indirect light emissions from layered ReS2-x Se x (0 <= x <= 2).
AB - ReS2 and ReSe2 have recently been enthusiastically studied owing to the specific
in-plane electrical, optical and structural anisotropy caused by their distorted
one-layer trigonal (1 T) phase, whereas other traditional transition-metal
dichalcogenides (TMDCs, e.g. MoS2 and WSe2) have a hexagonal structure. Because
of this special property, more and versatile nano-electronics and nano
optoelectronics devices can be developed. In this work, 2D materials in the
series ReS2-x Se x (0 <= x <= 2) have been successfully grown by the method of
chemical vapor transport. The direct and indirect resonant emissions of the
complete series of layers can be simultaneously detected by polarized micro
photoluminescence (MUPL) spectroscopy when the thickness of the ReS2-x Se x is
greater than ~70 nm. When it is less than 70 nm, only three direct excitonic
emissions-E 1ex, E 2ex and E Sex-are detected. For the thick (bulk) ReS2-x Se x ,
more stacking of the ReX2 monolayers even flattens and shifts the valence-band
maximum from Gamma to the other K- or M-related points, thus leading to the
coexistence of direct and indirect resonant light emissions from the c-plane
ReX2. The transmittance absorption edge of each bulk ReX2 (a few microns thick)
usually has a lower energy than those of the direct E 1ex and E 2ex excitonic
emissions to form indirect absorption. The coexistence of direct and indirect
emissions in ReX2 is a unique characteristic of a 2D layered semiconductor
possessing triclinic low symmetry.
PMID- 28516897
TI - Intrinsic valley polarization of magnetic VSe2 monolayers.
AB - Intrinsic valley polarization can be obtained in VSe2 monolayers with broken
inversion symmetry and time reversal symmetry. First-principles investigations
reveal that the magnitude of the valley splitting in magnetic VSe2 induced by
spin-orbit coupling reaches as high as 78.2 meV and can be linearly tuned by
biaxial strain. Besides conventional polarized light, hole doping or illumination
with light of proper frequency can offer effective routes to realize valley
polarization. Moreover, spin-orbit coupling in monolayer VSe2 breaks not only the
valley degeneracy but also the three-fold rotational symmetry in band structure.
The intrinsic and tunable valley splitting and the breaking of optical isotropy
bring additional benefits to valleytronic and optoelectronic applications.
PMID- 28516898
TI - Structural and magnetic properties of spin-1/2 dimer compound Cu2(IPA)2(DMF)(H2O)
with a large spin gap.
AB - We present the synthesis and a detailed investigation of structural and magnetic
properties of metal-organic compound Cu2(IPA)2(DMF)(H2O) by means of x-ray
diffraction, magnetization, and heat capacity measurements. Single crystals of
the title compound were synthesized by judicious selection of organic ligand and
employing a selective hydrothermal reaction route. It crystallizes in an
orthorhombic structure with space group Cmca. The structural analysis revealed
that two Cu2+ ions are held together by the organic component (-O-C-O-) in a
square paddle-wheel to form spin dimers which are aligned perpendicular to each
other and are further coupled through organic ligands (isophthalic acid) forming
two-dimensional layers. Temperature dependent magnetic susceptibility [Formula:
see text] could be described well using spin-1/2 dimer model. The spin
susceptibility [Formula: see text] shows an exponential decrease in the low
temperature region, below the broad maximum, confirming the singlet ground state
with a large spin gap of [Formula: see text] K. The heat capacity C p measured as
a function of temperature also confirms the absence of magnetic long-range-order
down to 2 K.
PMID- 28516899
TI - All-dielectric resonant cavity-enabled metals with broadband optical
transparency.
AB - Metal films with broadband optical transparency are desirable in many
optoelectronic devices, such as displays, smart windows, light-emitting diodes
and infrared detectors. As bare metal is opaque to light, this issue of
transparency attracts great scientific interest. In this work, we proposed and
demonstrated a feasible and universal approach for achieving broadband optical
transparent (BOT) metals by utilizing all-dielectric resonant cavities. Resonant
dielectrics provide optical cavity modes and couple strongly with the surface
plasmons of the metal film, and therefore produce a broadband near-unity optical
transparent window. The relative enhancement factor (EF) of light transmission
exceeds 3400% in comparison with that of pure metal film. Moreover, the
transparent metal motif can be realized by other common metals including gold
(Au), silver (Ag) and copper (Cu). These optical features together with the fully
retained electric and mechanical properties of a natural metal suggest that it
will have wide applications in optoelectronic devices.
PMID- 28516900
TI - Facile preparation of protonated hexaniobate nanosheets and its enhanced
photocatalytic activity.
AB - Exfoliated hexaniobate nanosheets E-H2K2Nb6O17-x (E-HKNO) with broad light
absorption (up to 850 nm) and high adsorption properties were prepared via ion
exchange and transient annealing processes with micron-size K4Nb6O17 powders as
the precursor. The as-prepared E-HKNO nanosheets show excellent visible light
photodegradation performances when compared to degussa P25, which was evaluated
in terms of degradation of Rhodamine B (Rh B). High adsorption and broad light
absorption characteristics could be attributed to the exfoliation behavior and
the reduction of surface Nb5+ to Nb4+, which was confirmed by x-ray photoelectron
spectroscopy (XPS) and Raman spectra. From the Mott-Schottky analysis, the E-HKNO
is an n-type semiconductor and has a higher flat band voltage (-0.46 V versus RHE
at pH = 7), compared with K4Nb6O17. In addition, the electrochemical impedance
spectroscopy (EIS) indicates that the E-HKNO nanosheets have an increased
semiconductor-electrolyte charge transfer resistance, which is not conducive to
the separation of photogenerated carriers (e--h+). Accordingly, a small amount of
holes scavenger (EDTA) was added to improve the photodegradation performance of
the E-HKNO, since the holes scavenger can inhibit the recombination of the
photogenerated carriers. This work provides not only a facile method for the
preparation of an efficient E-HKNO nanosheets photocatalyst, but also new
insights for further enhancing the photodegradation performance by adding trace
scavenger.
PMID- 28516901
TI - EEG source space analysis of the supervised factor analytic approach for the
classification of multi-directional arm movement.
AB - OBJECTIVE: In electroencephalography (EEG)-based brain-computer interface (BCI)
systems for motor control tasks the conventional practice is to decode motor
intentions by using scalp EEG. However, scalp EEG only reveals certain limited
information about the complex tasks of movement with a higher degree of freedom.
Therefore, our objective is to investigate the effectiveness of source-space EEG
in extracting relevant features that discriminate arm movement in multiple
directions. APPROACH: We have proposed a novel feature extraction algorithm based
on supervised factor analysis that models the data from source-space EEG. To this
end, we computed the features from the source dipoles confined to Brodmann areas
of interest (BA4a, BA4p and BA6). Further, we embedded class-wise labels of multi
direction (multi-class) source-space EEG to an unsupervised factor analysis to
make it into a supervised learning method. MAIN RESULTS: Our approach provided an
average decoding accuracy of 71% for the classification of hand movement in four
orthogonal directions, that is significantly higher (>10%) than the
classification accuracy obtained using state-of-the-art spatial pattern features
in sensor space. Also, the group analysis on the spectral characteristics of
source-space EEG indicates that the slow cortical potentials from a set of
cortical source dipoles reveal discriminative information regarding the movement
parameter, direction. SIGNIFICANCE: This study presents evidence that low
frequency components in the source space play an important role in movement
kinematics, and thus it may lead to new strategies for BCI-based
neurorehabilitation.
PMID- 28516902
TI - Role of Transient Receptor Potential Channels in Heart Transplantation: A
Potential Novel Therapeutic Target for Cardiac Allograft Vasculopathy.
AB - Heart transplantation has evolved as the criterion standard therapy for end-stage
heart failure, but its efficacy is limited by the development of cardiac
allograft vasculopathy (CAV), a unique and rapidly progressive form of
atherosclerosis in heart transplant recipients. Here, we briefly review the key
processes in the development of CAV during heart transplantation and highlight
the roles of transient receptor potential (TRP) channels in these processes
during heart transplantation. Understanding the roles of TRP channels in
contributing to the key procedures for the development of CAV during heart
transplantation could provide basic scientific knowledge for the development of
new preventive and therapeutic approaches to manage patients with CAV after heart
transplantation.
PMID- 28516905
TI - The effects of forest canopy shading and turbulence on boundary layer ozone.
AB - The chemistry of the Earth's atmosphere close to the surface is known to be
strongly influenced by vegetation. However, two critical aspects of the forest
environment have been neglected in the description of the large-scale influence
of forests on air pollution: the reduction of photolysis reaction rates and the
modification of vertical transport due to the presence of foliage. Here we show
that foliage shading and foliage-modified vertical diffusion have a profound
influence on atmospheric chemistry, both at the Earth's surface and extending
throughout the atmospheric boundary layer. The absence of these processes in
three-dimensional models may account for 59-72% of the positive bias in North
American surface ozone forecasts, and up to 97% of the bias in forested regions
within the continent. These processes are shown to have similar or greater
influence on surface ozone levels as climate change and current emissions policy
scenario simulations.
PMID- 28516903
TI - Molecular mechanism of Galphai activation by non-GPCR proteins with a Galpha
Binding and Activating motif.
AB - Heterotrimeric G proteins are quintessential signalling switches activated by
nucleotide exchange on Galpha. Although activation is predominantly carried out
by G-protein-coupled receptors (GPCRs), non-receptor guanine-nucleotide exchange
factors (GEFs) have emerged as critical signalling molecules and therapeutic
targets. Here we characterize the molecular mechanism of G-protein activation by
a family of non-receptor GEFs containing a Galpha-binding and -activating (GBA)
motif. We combine NMR spectroscopy, computational modelling and biochemistry to
map changes in Galpha caused by binding of GBA proteins with residue-level
resolution. We find that the GBA motif binds to the SwitchII/alpha3 cleft of
Galpha and induces changes in the G-1/P-loop and G-2 boxes (involved in phosphate
binding), but not in the G-4/G-5 boxes (guanine binding). Our findings reveal
that G-protein-binding and activation mechanisms are fundamentally different
between GBA proteins and GPCRs, and that GEF-mediated perturbation of nucleotide
phosphate binding is sufficient for Galpha activation.
PMID- 28516906
TI - Nanometric holograms based on a topological insulator material.
AB - Holography has extremely extensive applications in conventional optical
instruments spanning optical microscopy and imaging, three-dimensional displays
and metrology. To integrate holography with modern low-dimensional electronic
devices, holograms need to be thinned to a nanometric scale. However, to keep a
pronounced phase shift modulation, the thickness of holograms has been generally
limited to the optical wavelength scale, which hinders their integration with
ultrathin electronic devices. Here, we break this limit and achieve 60 nm
holograms using a topological insulator material. We discover that nanometric
topological insulator thin films act as an intrinsic optical resonant cavity due
to the unequal refractive indices in their metallic surfaces and bulk. The
resonant cavity leads to enhancement of phase shifts and thus the holographic
imaging. Our work paves a way towards integrating holography with flat electronic
devices for optical imaging, data storage and information security.
PMID- 28516904
TI - Lhx1/5 control dendritogenesis and spine morphogenesis of Purkinje cells via
regulation of Espin.
AB - In the cerebellar cortex, Purkinje cells (PCs) receive signals from different
inputs through their extensively branched dendrites and serve as an integration
centre. Defects in the dendritic development of PCs thus disrupt cerebellar
circuitry and cause ataxia. Here we report that specific inactivation of both
Lhx1 and Lhx5 in postnatal PCs results in ataxic mutant mice with abnormal
dendritic development. The PCs in the mutants have reduced expression of Espin,
an F-actin cytoskeleton regulator. We show that Espin expression is
transcriptionally activated by Lhx1/5. Downregulation of Espin leads to F-actin
mislocalization, thereby impairing dendritogenesis and dendritic spine maturation
in the PCs. The mutant PCs therefore fail to form proper synapses and show
aberrant electrophysiological properties. By overexpressing Espin, we can
successfully rescue the defects in the mutant PCs. Our findings suggest that
Lhx1/5, through regulating Espin expression, control dendritogenesis and spine
morphogenesis in postnatal PCs.
PMID- 28516907
TI - Vagal determinants of exercise capacity.
AB - Indirect measures of cardiac vagal activity are strongly associated with exercise
capacity, yet a causal relationship has not been established. Here we show that
in rats, genetic silencing of the largest population of brainstem vagal
preganglionic neurons residing in the brainstem's dorsal vagal motor nucleus
dramatically impairs exercise capacity, while optogenetic recruitment of the same
neuronal population enhances cardiac contractility and prolongs exercise
endurance. These data provide direct experimental evidence that parasympathetic
vagal drive generated by a defined CNS circuit determines the ability to
exercise. Decreased activity and/or gradual loss of the identified neuronal cell
group provides a neurophysiological basis for the progressive decline of exercise
capacity with aging and in diverse disease states.
PMID- 28516908
TI - An optimized strategy to measure protein stability highlights differences between
cold and hot unfolded states.
AB - Macromolecular crowding ought to stabilize folded forms of proteins, through an
excluded volume effect. This explanation has been questioned and observed effects
attributed to weak interactions with other cell components. Here we show
conclusively that protein stability is affected by volume exclusion and that the
effect is more pronounced when the crowder's size is closer to that of the
protein under study. Accurate evaluation of the volume exclusion effect is made
possible by the choice of yeast frataxin, a protein that undergoes cold
denaturation above zero degrees, because the unfolded form at low temperature is
more expanded than the corresponding one at high temperature. To achieve optimum
sensitivity to changes in stability we introduce an empirical parameter derived
from the stability curve. The large effect of PEG 20 on cold denaturation can be
explained by a change in water activity, according to Privalov's interpretation
of cold denaturation.
PMID- 28516909
TI - Heat guiding and focusing using ballistic phonon transport in phononic
nanostructures.
AB - Unlike classical heat diffusion at macroscale, nanoscale heat conduction can
occur without energy dissipation because phonons can ballistically travel in
straight lines for hundreds of nanometres. Nevertheless, despite recent
experimental evidence of such ballistic phonon transport, control over its
directionality, and thus its practical use, remains a challenge, as the
directions of individual phonons are chaotic. Here, we show a method to control
the directionality of ballistic phonon transport using silicon membranes with
arrays of holes. First, we demonstrate that the arrays of holes form fluxes of
phonons oriented in the same direction. Next, we use these nanostructures as
directional sources of ballistic phonons and couple the emitted phonons into
nanowires. Finally, we introduce thermal lens nanostructures, in which the
emitted phonons converge at the focal point, thus focusing heat into a spot of a
few hundred nanometres. These results motivate the concept of ray-like heat
manipulations at the nanoscale.
PMID- 28516912
TI - A complete tool set for molecular QTL discovery and analysis.
AB - Population scale studies combining genetic information with molecular phenotypes
(for example, gene expression) have become a standard to dissect the effects of
genetic variants onto organismal phenotypes. These kinds of data sets require
powerful, fast and versatile methods able to discover molecular Quantitative
Trait Loci (molQTL). Here we propose such a solution, QTLtools, a modular
framework that contains multiple new and well-established methods to prepare the
data, to discover proximal and distal molQTLs and, finally, to integrate them
with GWAS variants and functional annotations of the genome. We demonstrate its
utility by performing a complete expression QTL study in a few easy-to-perform
steps. QTLtools is open source and available at
https://qtltools.github.io/qtltools/.
PMID- 28516910
TI - Genetic architecture of epigenetic and neuronal ageing rates in human brain
regions.
AB - Identifying genes regulating the pace of epigenetic ageing represents a new
frontier in genome-wide association studies (GWASs). Here using 1,796 brain
samples from 1,163 individuals, we carry out a GWAS of two DNA methylation-based
biomarkers of brain age: the epigenetic ageing rate and estimated proportion of
neurons. Locus 17q11.2 is significantly associated (P=4.5 * 10-9) with the ageing
rate across five brain regions and harbours a cis-expression quantitative trait
locus for EFCAB5 (P=3.4 * 10-20). Locus 1p36.12 is significantly associated
(P=2.2 * 10-8) with epigenetic ageing of the prefrontal cortex, independent of
the proportion of neurons. Our GWAS of the proportion of neurons identified two
genome-wide significant loci (10q26 and 12p13.31) and resulted in a gene set that
overlaps significantly with sets found by GWAS of age-related macular
degeneration (P=1.4 * 10-12), ulcerative colitis (P<1.0 * 10-20), type 2 diabetes
(P=2.8 * 10-13), hip/waist circumference in men (P=1.1 * 10-9), schizophrenia
(P=1.6 * 10-9), cognitive decline (P=5.3 * 10-4) and Parkinson's disease (P=8.6 *
10-3).
PMID- 28516911
TI - Electrostatic melting in a single-molecule field-effect transistor with
applications in genomic identification.
AB - The study of biomolecular interactions at the single-molecule level holds great
potential for both basic science and biotechnology applications. Single-molecule
studies often rely on fluorescence-based reporting, with signal levels limited by
photon emission from single optical reporters. The point-functionalized carbon
nanotube transistor, known as the single-molecule field-effect transistor, is a
bioelectronics alternative based on intrinsic molecular charge that offers
significantly higher signal levels for detection. Such devices are effective for
characterizing DNA hybridization kinetics and thermodynamics and enabling
emerging applications in genomic identification. In this work, we show that
hybridization kinetics can be directly controlled by electrostatic bias applied
between the device and the surrounding electrolyte. We perform the first single
molecule experiments demonstrating the use of electrostatics to control molecular
binding. Using bias as a proxy for temperature, we demonstrate the feasibility of
detecting various concentrations of 20-nt target sequences from the Ebolavirus
nucleoprotein gene in a constant-temperature environment.
PMID- 28516913
TI - Self-folding origami at any energy scale.
AB - Programmable stiff sheets with a single low-energy folding motion have been
sought in fields ranging from the ancient art of origami to modern meta-materials
research. Despite such attention, only two extreme classes of crease patterns are
usually studied; special Miura-Ori-based zero-energy patterns, in which crease
folding requires no sheet bending, and random patterns with high-energy folding,
in which the sheet bends as much as creases fold. We present a physical approach
that allows systematic exploration of the entire space of crease patterns as a
function of the folding energy. Consequently, we uncover statistical results in
origami, finding the entropy of crease patterns of given folding energy. Notably,
we identify three classes of Mountain-Valley choices that have widely varying
'typical' folding energies. Our work opens up a wealth of experimentally relevant
self-folding origami designs not reliant on Miura-Ori, the Kawasaki condition or
any special symmetry in space.
PMID- 28516914
TI - Adenylate kinase hCINAP determines self-renewal of colorectal cancer stem cells
by facilitating LDHA phosphorylation.
AB - Targeting the specific metabolic phenotypes of colorectal cancer stem cells
(CRCSCs) is an innovative therapeutic strategy for colorectal cancer (CRC)
patients with poor prognosis and relapse. However, the context-dependent
metabolic traits of CRCSCs remain poorly elucidated. Here we report that
adenylate kinase hCINAP is overexpressed in CRC tissues. Depletion of hCINAP
inhibits invasion, self-renewal, tumorigenesis and chemoresistance of CRCSCs with
a loss of mesenchymal signature. Mechanistically, hCINAP binds to the C-terminal
domain of LDHA, the key regulator of glycolysis, and depends on its adenylate
kinase activity to promote LDHA phosphorylation at tyrosine 10, resulting in the
hyperactive Warburg effect and the lower cellular ROS level and conferring
metabolic advantage to CRCSC invasion. Moreover, hCINAP expression is positively
correlated with the level of Y10-phosphorylated LDHA in CRC patients. This study
identifies hCINAP as a potent modulator of metabolic reprogramming in CRCSCs and
a promising drug target for CRC invasion and metastasis.
PMID- 28516915
TI - Equilibrium oxygen storage capacity of ultrathin CeO2-delta depends non
monotonically on large biaxial strain.
AB - Elastic strain is being increasingly employed to enhance the catalytic properties
of mixed ion-electron conducting oxides. However, its effect on oxygen storage
capacity is not well established. Here, we fabricate ultrathin, coherently
strained films of CeO2-delta between 5.6% biaxial compression and 2.1% tension.
In situ ambient pressure X-ray photoelectron spectroscopy reveals up to a
fourfold enhancement in equilibrium oxygen storage capacity under both
compression and tension. This non-monotonic variation with strain departs from
the conventional wisdom based on a chemical expansion dominated behaviour.
Through depth profiling, film thickness variations and a coupled photoemission
thermodynamic analysis of space-charge effects, we show that the enhanced
reducibility is not dominated by interfacial effects. On the basis of ab initio
calculations of oxygen vacancy formation incorporating defect interactions and
vibrational contributions, we suggest that the non-monotonicity arises from the
tetragonal distortion under large biaxial strain. These results may guide the
rational engineering of multilayer and core-shell oxide nanomaterials.
PMID- 28516916
TI - Unified model for singlet fission within a non-conjugated covalent pentacene
dimer.
AB - When molecular dimers, crystalline films or molecular aggregates absorb a photon
to produce a singlet exciton, spin-allowed singlet fission may produce two
triplet excitons that can be used to generate two electron-hole pairs, leading to
a predicted ~50% enhancement in maximum solar cell performance. The singlet
fission mechanism is still not well understood. Here we report on the use of time
resolved optical and electron paramagnetic resonance spectroscopy to probe
singlet fission in a pentacene dimer linked by a non-conjugated spacer. We
observe the key intermediates in the singlet fission process, including the
formation and decay of a quintet state that precedes formation of the pentacene
triplet excitons. Using these combined data, we develop a single kinetic model
that describes the data over seven temporal orders of magnitude both at room and
cryogenic temperatures.
PMID- 28516918
TI - In Retrospect: Half a century of robust climate models.
PMID- 28516919
TI - Atomic physics: Quantum theory verified by experiment.
PMID- 28516921
TI - Behavioural economics: Occasional errors can benefit coordination.
PMID- 28516917
TI - Maternal age-dependent APC/C-mediated decrease in securin causes premature sister
chromatid separation in meiosis II.
AB - Sister chromatid attachment during meiosis II (MII) is maintained by securin
mediated inhibition of separase. In maternal ageing, oocytes show increased inter
sister kinetochore distance and premature sister chromatid separation (PSCS),
suggesting aberrant separase activity. Here, we find that MII oocytes from aged
mice have less securin than oocytes from young mice and that this reduction is
mediated by increased destruction by the anaphase promoting complex/cyclosome
(APC/C) during meiosis I (MI) exit. Inhibition of the spindle assembly checkpoint
(SAC) kinase, Mps1, during MI exit in young oocytes replicates this phenotype.
Further, over-expression of securin or Mps1 protects against the age-related
increase in inter-sister kinetochore distance and PSCS. These findings show that
maternal ageing compromises the oocyte SAC-APC/C axis leading to a decrease in
securin that ultimately causes sister chromatid cohesion loss. Manipulating this
axis and/or increasing securin may provide novel therapeutic approaches to
alleviating the risk of oocyte aneuploidy in maternal ageing.
PMID- 28516920
TI - China: Rail network must protect giant pandas.
PMID- 28516922
TI - Multidisciplinarity: Widen discipline span of Nature papers.
PMID- 28516925
TI - Global health: Boost multinational clinical research.
PMID- 28516929
TI - Hans Dehmelt (1922-2017).
PMID- 28516927
TI - Locally noisy autonomous agents improve global human coordination in network
experiments.
AB - Coordination in groups faces a sub-optimization problem and theory suggests that
some randomness may help to achieve global optima. Here we performed experiments
involving a networked colour coordination game in which groups of humans
interacted with autonomous software agents (known as bots). Subjects (n = 4,000)
were embedded in networks (n = 230) of 20 nodes, to which we sometimes added 3
bots. The bots were programmed with varying levels of behavioural randomness and
different geodesic locations. We show that bots acting with small levels of
random noise and placed in central locations meaningfully improve the collective
performance of human groups, accelerating the median solution time by 55.6%. This
is especially the case when the coordination problem is hard. Behavioural
randomness worked not only by making the task of humans to whom the bots were
connected easier, but also by affecting the gameplay of the humans among
themselves and hence creating further cascades of benefit in global coordination
in these heterogeneous systems.
PMID- 28516930
TI - Seismology: Japan must admit it can't predict quakes.
PMID- 28516932
TI - Correction.
PMID- 28516933
TI - Experimental characterization of a quantum many-body system via higher-order
correlations.
AB - Quantum systems can be characterized by their correlations. Higher-order (larger
than second order) correlations, and the ways in which they can be decomposed
into correlations of lower order, provide important information about the system,
its structure, its interactions and its complexity. The measurement of such
correlation functions is therefore an essential tool for reading, verifying and
characterizing quantum simulations. Although higher-order correlation functions
are frequently used in theoretical calculations, so far mainly correlations up to
second order have been studied experimentally. Here we study a pair of tunnel
coupled one-dimensional atomic superfluids and characterize the corresponding
quantum many-body problem by measuring correlation functions. We extract phase
correlation functions up to tenth order from interference patterns and analyse
whether, and under what conditions, these functions factorize into correlations
of lower order. This analysis characterizes the essential features of our system,
the relevant quasiparticles, their interactions and topologically distinct vacua.
From our data we conclude that in thermal equilibrium our system can be seen as a
quantum simulator of the sine-Gordon model, relevant for diverse disciplines
ranging from particle physics to condensed matter. The measurement and evaluation
of higher-order correlation functions can easily be generalized to other systems
and to study correlations of any other observable such as density, spin and
magnetization. It therefore represents a general method for analysing quantum
many-body systems from experimental data.
PMID- 28516934
TI - Rescue old data before it's too late.
PMID- 28516935
TI - How Trump's science cuts could hurt states that voted for him.
PMID- 28516937
TI - Ebola outbreak in the Congo, tuberculosis drug resistance in Russia and GM
mustard seeds in India.
PMID- 28516936
TI - Biology needs more staff scientists.
PMID- 28516938
TI - Keep doors open for constructive dialogue between religion and science.
PMID- 28516939
TI - China cracks down on fake data in drug trials.
PMID- 28516940
TI - The United States must act quickly to control the use of e-cigarettes.
PMID- 28516941
TI - The wooden skyscrapers that could help to cool the planet.
PMID- 28516942
TI - Ancient-genome study finds Bronze Age 'Beaker culture' invaded Britain.
PMID- 28516943
TI - Why US nuclear sites are a ticking time bomb.
PMID- 28516944
TI - Century-old tumours offer rare cancer clues.
PMID- 28516945
TI - Geneticists enlist engineered virus and CRISPR to battle citrus disease.
PMID- 28516947
TI - Artificial local magnetic field inhomogeneity enhances T2 relaxivity.
AB - Clustering of magnetic nanoparticles (MNPs) is perhaps the most effective, yet
intriguing strategy to enhance T2 relaxivity in magnetic resonance imaging (MRI).
However, the underlying mechanism is still not fully understood and the attempts
to generalize the classic outersphere theory from single particles to clusters
have been found to be inadequate. Here we show that clustering of MNPs enhances
local field inhomogeneity due to reduced field symmetry, which can be further
elevated by artificially involving iron oxide NPs with heterogeneous geometries
in terms of size and shape. The r2 values of iron oxide clusters and Landau
Lifshitz-Gilbert simulations confirmed our hypothesis, indicating that solving
magnetic field inhomogeneity may become a powerful way to build correlation
between magnetization and T2 relaxivity of MNPs, especially magnetic clusters.
This study provides a simple yet distinct mechanism to interpret T2 relaxivity of
MNPs, which is crucial to the design of high-performance MRI contrast agents.
PMID- 28516946
TI - Ccl2/Ccr2 signalling recruits a distinct fetal microchimeric population that
rescues delayed maternal wound healing.
AB - Foetal microchimeric cells (FMCs) traffic into maternal circulation during
pregnancy and persist for decades after delivery. Upon maternal injury, FMCs
migrate to affected sites where they participate in tissue healing. However, the
specific signals regulating the trafficking of FMCs to injury sites had to be
identified. Here we report that, in mice, a subset of FMCs implicated in tissue
repair displays CD11b+ CD34+ CD31+ phenotype and highly express C-C chemokine
receptor 2 (Ccr2). The Ccr2 ligand chemokine ligand 2 (Ccl2) enhances the
recruitment of FMCs to maternal wounds where these cells transdifferentiate into
endothelial cells and stimulate angiogenesis through Cxcl1 secretion. Ccl2
administration improves delayed maternal wound healing in pregnant and postpartum
mice but never in virgin ones. This role of Ccl2/Ccr2 signalling opens new
strategies for tissue repair through natural stem cell therapy, a concept that
can be later applied to other types of maternal diseases.
PMID- 28516949
TI - Paroxysmal nocturnal haemoglobinuria.
AB - Paroxysmal nocturnal haemoglobinuria (PNH) is a clonal haematopoietic stem cell
(HSC) disease that presents with haemolytic anaemia, thrombosis and smooth muscle
dystonias, as well as bone marrow failure in some cases. PNH is caused by somatic
mutations in PIGA (which encodes phosphatidylinositol N
acetylglucosaminyltransferase subunit A) in one or more HSC clones. The gene
product of PIGA is required for the biosynthesis of glycosylphosphatidylinositol
(GPI) anchors; thus, PIGA mutations lead to a deficiency of GPI-anchored
proteins, such as complement decay-accelerating factor (also known as CD55) and
CD59 glycoprotein (CD59), which are both complement inhibitors. Clinical
manifestations of PNH occur when a HSC clone carrying somatic PIGA mutations
acquires a growth advantage and differentiates, generating mature blood cells
that are deficient of GPI-anchored proteins. The loss of CD55 and CD59 renders
PNH erythrocytes susceptible to intravascular haemolysis, which can lead to
thrombosis and to much of the morbidity and mortality of PNH. The accumulation of
anaphylatoxins (such as C5a) from complement activation might also have a role.
The natural history of PNH is highly variable, ranging from quiescent to life
threatening. Therapeutic strategies include terminal complement blockade and bone
marrow transplantation. Eculizumab, a monoclonal antibody complement inhibitor,
is highly effective and the only licensed therapy for PNH.
PMID- 28516950
TI - High conductance values in pi-folded molecular junctions.
AB - Folding processes play a crucial role in the development of function in
biomacromolecules. Recreating this feature on synthetic systems would not only
allow understanding and reproducing biological functions but also developing new
functions. This has inspired the development of conformationally ordered
synthetic oligomers known as foldamers. Herein, a new family of foldamers,
consisting of an increasing number of anthracene units that adopt a folded
sigmoidal conformation by a combination of intramolecular hydrogen bonds and
aromatic interactions, is reported. Such folding process opens up an efficient
through-space charge transport channel across the interacting anthracene
moieties. In fact, single-molecule conductance measurements carried out on this
series of foldamers, using the scanning tunnelling microscopy-based break
junction technique, reveal exceptionally high conductance values in the order of
10-1 G0 and a low length decay constant of 0.02 A-1 that exceed the values
observed in molecular junctions that make use of through-space charge transport
pathways.
PMID- 28516951
TI - Improving 10-deacetylbaccatin III-10-beta-O-acetyltransferase catalytic fitness
for Taxol production.
AB - The natural concentration of the anticancer drug Taxol is about 0.02% in yew
trees, whereas that of its analogue 7-beta-xylosyl-10-deacetyltaxol is up to
0.5%. While this compound is not an intermediate in Taxol biosynthetic route, it
can be converted into Taxol by de-glycosylation and acetylation. Here, we improve
the catalytic efficiency of 10-deacetylbaccatin III-10-O-acetyltransferase (DBAT)
of Taxus towards 10-deacetyltaxol, a de-glycosylated derivative of 7-beta-xylosyl
10-deacetyltaxol to generate Taxol using mutagenesis. We generate a three
dimensional structure of DBAT and identify its active site using alanine scanning
and design a double DBAT mutant (DBATG38R/F301V) with a catalytic efficiency
approximately six times higher than that of the wild-type. We combine this mutant
with a beta-xylosidase to obtain an in vitro one-pot conversion of 7-beta-xylosyl
10-deacetyltaxol to Taxol yielding 0.64 mg ml-1 Taxol in 50 ml at 15 h. This
approach represents a promising environmentally friendly alternative for Taxol
production from an abundant analogue.
PMID- 28516952
TI - Solid frustrated-Lewis-pair catalysts constructed by regulations on surface
defects of porous nanorods of CeO2.
AB - Identification on catalytic sites of heterogeneous catalysts at atomic level is
important to understand catalytic mechanism. Surface engineering on defects of
metal oxides can construct new active sites and regulate catalytic activity and
selectivity. Here we outline the strategy by controlling surface defects of
nanoceria to create the solid frustrated Lewis pair (FLP) metal oxide for
efficient hydrogenation of alkenes and alkynes. Porous nanorods of ceria (PN
CeO2) with a high concentration of surface defects construct new Lewis acidic
sites by two adjacent surface Ce3+. The neighbouring surface lattice oxygen as
Lewis base and constructed Lewis acid create solid FLP site due to the rigid
lattice of ceria, which can easily dissociate H-H bond with low activation energy
of 0.17 eV.
PMID- 28516953
TI - Signal recognition particle prevents N-terminal processing of bacterial membrane
proteins.
AB - Bacterial proteins are synthesized with an N-formylated amino-terminal
methionine, and N-formylated peptides elicit innate-immunity responses against
bacterial infections. However, the source of these formylated peptides is not
clear, as most bacterial proteins are co-translationally deformylated by peptide
deformylase. Here we develop a deformylation assay with translating ribosomes as
substrates, to show that the binding of the signal recognition particle (SRP) to
signal sequences in nascent proteins on the ribosome prevents deformylation,
whereas deformylation of nascent proteins without signal sequence is not
affected. Deformylation and its inhibition by SRP are not influenced by trigger
factor, a chaperone that interacts with nascent chains on the ribosome. We
propose that bacterial inner-membrane proteins, in particular those with N-out
topology, can retain their N-terminal formyl group during cotranslational
membrane insertion and supply formylated peptides during bacterial infections.
PMID- 28516955
TI - Spectral correlations in a random distributed feedback fibre laser.
AB - Random distributed feedback fibre lasers belong to the class of random lasers,
where the feedback is provided by amplified Rayleigh scattering on sub-micron
refractive index inhomogenities randomly distributed over the fibre length.
Despite the elastic nature of Rayleigh scattering, the feedback mechanism has
been insofar deemed incoherent, which corresponds to the commonly observed smooth
generation spectra. Here, using a real-time spectral measurement technique based
on a scanning Fabry-Perot interferometer, we observe long-living narrowband
components in the random fibre laser's spectrum. Statistical analysis of the ~104
single-scan spectra reveals a preferential interspacing for the components and
their anticorrelation in intensities. Furthermore, using mutual information
analysis, we confirm the existence of nonlinear correlations between different
parts of the random fibre laser spectra. The existence of such narrowband
spectral components, together with their observed correlations, establishes a
long-missing parallel between the fields of random fibre lasers and conventional
random lasers.
PMID- 28516954
TI - Histone deacetylase 10 structure and molecular function as a polyamine
deacetylase.
AB - Cationic polyamines such as spermidine and spermine are critical in all forms of
life, as they regulate the function of biological macromolecules. Intracellular
polyamine metabolism is regulated by reversible acetylation and dysregulated
polyamine metabolism is associated with neoplastic diseases such as colon cancer,
prostate cancer and neuroblastoma. Here we report that histone deacetylase 10
(HDAC10) is a robust polyamine deacetylase, using recombinant enzymes from Homo
sapiens (human) and Danio rerio (zebrafish). The 2.85 A-resolution crystal
structure of zebrafish HDAC10 complexed with a transition-state analogue
inhibitor reveals that a glutamate gatekeeper and a sterically constricted active
site confer specificity for N8-acetylspermidine hydrolysis and disfavour
acetyllysine hydrolysis. Both HDAC10 and spermidine are known to promote cellular
survival through autophagy. Accordingly, this work sets a foundation for studying
the chemical biology of autophagy through the structure-based design of
inhibitors that may also serve as new leads for cancer chemotherapy.
PMID- 28516958
TI - The origin and degassing history of the Earth's atmosphere revealed by Archean
xenon.
AB - Xenon (Xe) is an exceptional tracer for investigating the origin and fate of
volatile elements on Earth. The initial isotopic composition of atmospheric Xe
remains unknown, as do the mechanisms involved in its depletion and isotopic
fractionation compared with other reservoirs in the solar system. Here we present
high precision analyses of noble gases trapped in fluid inclusions of Archean
quartz (Barberton, South Africa) that reveal the isotopic composition of the
paleo-atmosphere at ~3.3 Ga. The Archean atmospheric Xe is mass-dependently
fractionated by 12.9+/-2.4 0/00 u-1 (+/- 2sigma, s.d.) relative to the modern
atmosphere. The lower than today 129Xe excess requires a degassing rate of
radiogenic Xe from the mantle higher than at present. The primordial Xe component
delivered to the Earth's atmosphere is distinct from Solar or Chondritic Xe but
similar to a theoretical component called U-Xe. Comets may have brought this
component to the Earth's atmosphere during the last stages of terrestrial
accretion.
PMID- 28516956
TI - Selective BET bromodomain inhibition as an antifungal therapeutic strategy.
AB - Invasive fungal infections cause significant morbidity and mortality among
immunocompromised individuals, posing an urgent need for new antifungal
therapeutic strategies. Here we investigate a chromatin-interacting module, the
bromodomain (BD) from the BET family of proteins, as a potential antifungal
target in Candida albicans, a major human fungal pathogen. We show that the BET
protein Bdf1 is essential in C. albicans and that mutations inactivating its two
BDs result in a loss of viability in vitro and decreased virulence in mice. We
report small-molecule compounds that inhibit C. albicans Bdf1 with high
selectivity over human BDs. Crystal structures of the Bdf1 BDs reveal binding
modes for these inhibitors that are sterically incompatible with the human BET
binding pockets. Furthermore, we report a dibenzothiazepinone compound that
phenocopies the effects of a Bdf1 BD-inactivating mutation on C. albicans
viability. These findings establish BET inhibition as a promising antifungal
therapeutic strategy and identify Bdf1 as an antifungal drug target that can be
selectively inhibited without antagonizing human BET function.
PMID- 28516957
TI - ASXL2 is essential for haematopoiesis and acts as a haploinsufficient tumour
suppressor in leukemia.
AB - Additional sex combs-like (ASXL) proteins are mammalian homologues of additional
sex combs (Asx), a regulator of trithorax and polycomb function in Drosophila.
While there has been great interest in ASXL1 due to its frequent mutation in
leukemia, little is known about its paralog ASXL2, which is frequently mutated in
acute myeloid leukemia patients bearing the RUNX1-RUNX1T1 (AML1-ETO) fusion. Here
we report that ASXL2 is required for normal haematopoiesis with distinct, non
overlapping effects from ASXL1 and acts as a haploinsufficient tumour suppressor.
While Asxl2 was required for normal haematopoietic stem cell self-renewal, Asxl2
loss promoted AML1-ETO leukemogenesis. Moreover, ASXL2 target genes strongly
overlapped with those of RUNX1 and AML1-ETO and ASXL2 loss was associated with
increased chromatin accessibility at putative enhancers of key leukemogenic loci.
These data reveal that Asxl2 is a critical regulator of haematopoiesis and
mediates transcriptional effects that promote leukemogenesis driven by AML1-ETO.
PMID- 28516960
TI - Clinicopathologic idiosyncrasies of nasopharyngeal cancer in a moderate-risk
Mediterranean region.
AB - Cancer of the nasopharynx displays an unparalleled skewness of its epidemiologic,
pathogenic and clinico-prognostic characteristics depending on the geographic
location. Between the endemic and sporadic forms, which occur in Southeastern
Asia and Northern America, respectively, intermediate incidence is noted around
the Mediterranean. This study describes the patterns of the disease affecting the
population of Western Greece. The records of 70 patients with nasopharyngeal
cancer diagnosed in a single institution between 1994-2014 were retrospectively
reviewed. Primary treatment involved irradiation with or without concurrent
chemotherapy. Demographic data, patient risk factors, tumour parameters, clinical
presentation and treatment outcomes were assessed for potential
intercorrelations. Overall (OS) and disease-specific (DSS) 5-year survival rates
were determined. Possible predictors of survival were tested on univariate and
multivariate analysis. WHO-type 3 histopathology was diagnosed predominantly
(74.3%) and associated significantly with nasal symptomatology upon presentation
(p = 0.050), metastatic lymphadenopathy (p = 0.028), advanced clinical stage (p =
0.009) and complete response to initial treatment (p = 0.018). Univariate
analysis revealed a negative prognostic significance for older age (OS, p = 0.029
DSS, p = 0.041), poor response to treatment (OS & DSS p < 0.001) and cancer
recurrence (OS, p = 0.003 DSS, p = 0.001). On multivariate analysis, disease
relapse maintained its adverse effect (HR 7.442, 95% CI 2.199-25.187, p = 0.001).
In conclusion, among nasopharyngeal carcinomas arising in western Greece,
lymphoepitheliomas manifest a distinct clinical behaviour, so that their latest
grouping along with WHO-type 2 tumours into the "non-keratinising" category may
not apply. Regardless of pathology, cancer recurrence after initial remission is
a severe event.
PMID- 28516959
TI - Adaptive psychological structure in childhood hearing impairment: audiological
correlations.
AB - The present research deals with the clinical and social problems present during
linguistic and cognitive development of deaf children. Currently, the development
of Theory of Mind represents an important research field in deafness studies.
These international studies highlighted a significant alteration in the
development of Theory of Mind in deaf children compared to normal hearing
children, especially in cases of congenital or preverbal hearing loss. In
particular, the research focuses on the skills of deaf children in recognising
emotions and desires, through both perceptive and cognitive methods, by
evaluation of psycho-cognitive skills of children with severe hearing loss using
a set of questions to be administered to hearing loss patients. The experiment
was performed on a group composed of 10 children (5 males and 5 females) aged 4
to 9 years and 54 to 108 months, affected by bilateral congenital hearing loss
(severe to total), or hearing loss that developed in preverbal children the year
before entering elementary school, or during the fourth year of elementary
school. The selection criteria were based on: audiologic evaluation, neuro
psychological tests administered to assess general, cognitive as well as praxis
and perceptive abilities, and clinical observations performed to assess
psychopathology using tests that assess development of both visual perceptive
(Coloured Progressive Matrices) and graphic representational abilities (Test of
Human Figure Drawings and the Family Drawing Test). The instrument "cognitive"
was the "Deaf Children Series", arranged by us, that consists of a mental status
examination (MSE) that evaluates: level of cognitive (knowledge-related) ability,
emotional mood, and speech and thought patterns at the time of evaluation. Deaf
children show a reduced responsiveness to the expressions of sadness on the
perceptive side. Through the test, we observed a psychodynamic defense mechanism
considering perceptive understanding performance. On the contrary, in normal
hearing children, the emotion 'fear' is the most difficult to identify. Deaf
children seem to be more susceptible to recognition of visual emotions.
Furthermore, deaf children present significant problem-solving skills and
emotional recognition skills, possibly as a result of their hearing impairment.
PMID- 28516962
TI - Design of a customised bridging mandibular prosthesis for complex reconstruction:
a pilot study.
AB - The gold standard for mandibular reconstruction is universally recognised and
consists of the replacement of the bony part of the mandible with a bony
microvascular free flap supported by a reconstructive plate. Although this
procedure is feasible and reproducible in most patients, at times poor
oncological prognosis or poor performance status force surgeons to consider other
reconstructive solutions. In these cases, the main alternative in reconstructing
a mandibular defect is represented by bridging plates combined with soft tissue
flaps. However, repairing a mandibular defect with a reconstructive plate only
can lead to a series of diverse complications. The most frequent complications
reported are rupture and oral exposure of the plate. In this paper, we describe a
new method for mandibular reconstruction using a customised bridging mandibular
prosthesis (CBMP) without bone free flap.
PMID- 28516963
TI - The endoscopic evaluation of the oral phase of swallowing (Oral-FEES, O-FEES): a
pilot study of the clinical use of a new procedure.
AB - Oral FEES (O-FEES) is an endoscopic procedure conceived to directly visualise the
oral phase of swallowing. In the perspective of clinical use, the feasibility,
safety and acceptability of O-FEES has been evaluated. Subsequently, the
procedure was compared with the radiological gold standard. The acceptability of
O-FEES was compared to that of FEES using a 10 point questionnaire submitted to a
sample of 52 outpatients complaining of swallowing disorders. Repeated measure
analysis of variance (rm-ANOVA) models were used to test the mean difference of
acceptability in the same subjects after FEES and O-FEES. Subsequently, another
sample of 8 male outpatients underwent a simultaneous O-FEES and
videofluoroscopic study (VFSS). The inter-rater reliability using 10 radiological
landmarks, compared to O-FEES, was blindly determined between two raters. Inter
rater agreement between the two judges for O-FEES and VFSS scores was assessed
with the single score intra-class correlation coefficient (ICC). Differences
between FEES and O-FEES answers for each question and among all the items
considered overall were statistically significant (rm-ANOVA; F-statistic p <
0.001). The inter-rater agreement concerning endoscopic and radiological
evaluations between the two raters showed strong values of intra-class
correlation coefficient (ICC) (95% confidence interval): 0.875 (0.373-0.979) and
0.921 (0.542-0.986), respectively. The Bland-Altman test showed a bias of -0.24
(95% limits of agreement; -1.77 to +1.19), which suggests that both methods
produced almost identical results. In clinical practice and compared with FEES, O
FEES is a well tolerated and safe procedure. Compared with the radiological gold
standard, O-FEES offers reliable information about oral preparation and oral
propulsion of the bolus.
PMID- 28516964
TI - Barbed reposition pharyngoplasty in multilevel robotic surgery for obstructive
sleep apnoea.
AB - The surgical treatment of obstructive sleep apnoea in patients who are non
compliant with continuous positive airway pressure therapy still represents a
valid alternative. In recent years, the multilevel approach is becoming more
diffuse in routine surgical practice, especially since the introduction of
transoral robotic surgery. Barbed reposition pharyngoplasty in multilevel robotic
surgery for OSA may represent a valid option to surgically approach the soft
palate. Herein, we describe the technique and preliminary results of our
experience.
PMID- 28516961
TI - Supracricoid partial laryngectomy with crico-hyoido-epiglottopexy for glottic
carcinoma with anterior commissure involvement.
AB - Glottic cancers discovered at an early stage (T1-T2) can be treated with either
radiotherapy or surgery. The aim of our study is to analyse survival and
functional results of supra-cricoid partial laryngectomy (SCPL) with crico-hyoido
epiglottopexy (CHEP) as surgical treatment for glottic carcinoma with anterior
commissure involvement. We performed a retrospective study (1996-2013) which
included patients who underwent SCPL-CHEP for glottic squamous cell carcinoma
with involvement of the anterior commissure. Before surgery, all patients
underwent staging including head, neck and chest CT-scan with contrast injection
as well as suspension laryngoscopy under general anaesthesia. A total of 53
patients were included. The median follow-up period was 124 months. Tumour
resection was complete in 96.2% of cases. The overall, specific and recurrence
free survival rates at 5 years were, respectively, 93.7%, 95.6% and 87.7%. The
average period of hospitalisation was 18 days. The average time elapsed before
decannulation and before restoration of oral feeding were 15 and 18 days,
respectively. SCPL-CHEP is an important option for laryngeal surgical
preservation. It allows adequate disease control as well as good functional
results as long as the indications are well respected and the surgical techniques
are mastered.
PMID- 28516965
TI - Benefits of active middle ear implants over hearing aids in patients with sloping
high tone hearing loss: comparison with hearing aids.
AB - In this retrospective chart review we compared the subjective and objective
benefits of active middle ear implants (AMEIs) with conventional hearing aids
(HAs) in patients with sloping high tone hearing loss. Thirty-four patients with
sensorineural hearing loss were treated with AMEIs. Of these, six had sloping
high tone hearing loss and had worn an HA for more than 6 months. Objective
assessments, a pure-tone audiogram, as well as a word recognition test, and the
Korean version of the Hearing in Noise Test (K-HINT), and a subjective
assessment, the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire,
were performed. Tests were conducted under three circumstances: 1) the unaided
state before surgery; 2) the HA-aided state before surgery; and 3) the AMEI-aided
state 3 months after surgery. The average high-frequency hearing gain (>= 2 kHz)
was significantly better with AMEIs than with HAs. Although the result had no
statistical significance, AMEIs showed a superior word recognition score (WRS)
compared to HAs. However, the most comfortable hearing level at which the WRS was
tested was significantly decreased with an AMEI compared to an HA. In the K-HINT,
patients with an AMEI showed greater recognition than those fitted with an HA
under both quiet and noisy conditions. The APAHB scores revealed that patients
were more satisfied with an AMEI rather than an HA on all subscales. The use of
vibroplasty in patients with sloping high tone loss resulted in positive hearing
outcomes when compared to conventional HAs. Based on the data from this study,
AMEIs provided better objective and subjective results and could, therefore, be a
better alternative for the treatment of sloping hearing loss.
PMID- 28516966
TI - Expanded transcanal transpromontorial approach to the internal auditory canal and
cerebellopontine angle: a cadaveric study.
AB - The aim of this paper is to describe and evaluate the feasibility of an expanded
endoscopic transcanal transpromotorial approach (ExpTTA) to the internal auditory
canal and the cerebellopontine angle. To this end, we performed a cadaveric
dissection study in September 2015. In total, 2 heads (4 sides) were dissected
focusing on anatomical landmarks and surgical feasibility. Data from dissections
were reviewed and analysed for further consideration. In all 4 sides of the
cadavers the procedure was feasible. In all cadavers, it was necessary to
extensively drill the temporo-mandibular joint and to calibrate the external ear
canal to allow adequate room to manoeuver the instruments and optics and to
comfortably access the cerebellopontine angle. In addition, thorough
skeletonisation of the carotid artery and the jugular bulb were necessary for the
same purpose. In conclusion, ExpTTA appeared to be successful to access the
internal auditory canal and cerebellopontine angle region. Potential extensive
and routine application of this type of approach in lateral skull base surgery
will depend on the development of technology and surgical refinements and on the
diffusion of skull base endoscopic skills among otolaryngologists and
neurosurgical community.
PMID- 28516967
TI - Body-worn triaxial accelerometer coherence and reliability related to static
posturography in unilateral vestibular failure.
AB - Since changes in vestibular function may be one cause of disequilibrium, major
advances in measuring postural control and sensory integration in vestibular
impairments have been achieved by using posturography. However, in order to
overcome problems related to this type of technology, body-worn accelerometers
(ACC) have been proposed as a portable, low-cost alternative to posturography for
measurements of postural sway in a friendly and ecologic environment. Due to the
fact that no study to date has shown the experimental validity of ACC-based
measures of body sway with respect to posturography for subjects with vestibular
deficits, the aim of the present study was: i) to develop and validate a
practical tool that can allow clinicians to measure postural sway derangements in
an otoneurological setting by ACC, and ii) to provide reliable, sensitive and
accurate automatic analysis of sway that could help in discriminating unilateral
vestibular failure (UVF) patients. Thus, a group of 13 patients (seven females, 6
males; mean age 48.6 +/- 6.4 years) affected for at least 6 months by UVF and 13
matched healthy subjects were instructed to maintain an upright position during a
static forceplate-based posturography (FBP) acquisition while wearing a Movit(r)
sensor (by Captiks) with 3-D accelerometers mounted on the posterior trunk near
the body centre of mass. Pearson product moment correlation demonstrated a high
level of correspondence of four time-domain and three frequency-domain measures
extracted by ACC and FBP testing; in addition, t-test demonstrated that two ACC
based time- and frequency-domain parameters were reliable measures in
discriminating UVF subjects. These aspects, overall, should further highlight the
attention of clinicians and researchers to this kind of sway recording technique
in the field of otoneurological disorders by considering the possibility to
enrich the amount of quantitative and qualitative information useful for
discrimination, diagnosis and treatment of UVF. In conclusion, we believe the
present ACC-based measurement of sway offers a patient-friendly, reliable,
inexpensive and efficient alternative recording technique that is useful -
together with clinical balance and mobility tests - in various circumstances, as
well as in outcome studies involving diagnosis, follow-up and rehabilitation of
UVF patients.
PMID- 28516968
TI - Preliminary experience with 4K ultra-high definition endoscope: analysis of pros
and cons in skull base surgery.
AB - During the last two decades endoscopic skull base surgery observed a continuous
technical and technological development 3D endoscopy and ultra High Definition
(HD) endoscopy have provided great advances in terms of visualisation and spatial
resolution. Ultra-high definition (UHD) 4K systems, recently introduced in the
clinical practice, will shape next steps forward especially in skull base surgery
field. Patients were operated on through transnasal transsphenoidal endoscopic
approaches performed using Olympus NBI 4K UHD endoscope with a 4 mm 0 degrees
Ultra Telescope, 300 W xenon lamp (CLV-S400) predisposed for narrow band imaging
(NBI) technology connected through a camera head to a high-quality control unit
(OTV-S400 - VISERA 4K UHD) (Olympus Corporation, Tokyo, Japan). Two screens are
used, one 31" Monitor - (LMD-X310S) and one main ultra-HD 55" screen optimised
for UHD image reproduction (LMD-X550S). In selected cases, we used a navigation
system (Stealthstation S7, Medtronic, Minneapolis, MN, US). We evaluated 22
pituitary adenomas (86.3% macroadenomas; 13.7% microadenomas). 50% were not
functional (NF), 22.8% GH, 18.2% ACTH, 9% PRL-secreting. Three of 22 were
recurrences. In 91% of cases we achieved total removal, while in 9% near total
resection. A mean follow-up of 187 days and average length of hospitalisation was
3.09 +/- 0.61 days. Surgical duration was 128.18+/- 30.74 minutes. We experienced
only 1 case of intraoperative low flow fistula with no further complications.
None of the cases required any post- or intraoperative blood transfusion. The
visualisation and high resolution of the operative field provided a very detailed
view of all anatomical structures and pathologies allowing an improvement in
safety and efficacy of the surgical procedure. The operative time was similar to
the standard 2D HD and 3D procedures and the physical strain was also comparable
to others in terms of ergonomics and weight.
PMID- 28516969
TI - Voluminous laryngeal schwannoma excision with a mini-invasive external approach:
a case report.
AB - Laryngeal schwannomas are extremely uncommon. We present a case of bulky
supraglottic schwannoma with involvement of the preepiglottic and superior
paraglottic spaces. Clinical findings, computed tomography and magnetic resonance
images are presented. These characteristics are typical, however not specific to
schwannomas. For definitive diagnosis, histology and immunohistochemistry are
necessary. We present an external mini-invasive approach that allowed us to both
obtain diagnosis and provide definitive treatment for this kind of voluminous
laryngeal tumour.
PMID- 28516970
TI - Diagnostic work-up in obstructive and inflammatory salivary gland disorders.
AB - Inflammatory and obstructive disorders of the salivary glands are caused by very
different pathological conditions affecting the gland tissue and/or the excretory
system. The clinical setting is essential to address the appropriate diagnostic
imaging work-up. According to history and physical examination, four main
clinical scenarios can be recognised: (1) acute generalised swelling of major
salivary glands; (2) acute swelling of a single major salivary gland; (3) chronic
generalised swelling of major salivary glands, associated or not with "dry
mouth"; (4) chronic or prolonged swelling of a single major salivary gland. The
algorithm for imaging salivary glands depends on the scenario with which the
patient presents to the clinician. Imaging is essential to confirm clinical
diagnosis, define the extent of the disease and identify complications. Imaging
techniques include ultrasound (US), computed tomography (CT) and magnetic
resonance (MR) with MR sialography.
PMID- 28516971
TI - Salivary biomarkers and proteomics: future diagnostic and clinical utilities.
AB - Saliva testing is a non-invasive and inexpensive test that can serve as a source
of information useful for diagnosis of disease. As we enter the era of genomic
technologies and -omic research, collection of saliva has increased. Recent
proteomic platforms have analysed the human salivary proteome and characterised
about 3000 differentially expressed proteins and peptides: in saliva, more than
90% of proteins in weight are derived from the secretion of three couples of
"major" glands; all the other components are derived from minor glands, gingival
crevicular fluid, mucosal exudates and oral microflora. The most common aim of
proteomic analysis is to discriminate between physiological and pathological
conditions. A proteomic protocol to analyze the whole saliva proteome is not
currently available. It is possible distinguish two type of proteomic platforms:
top-down proteomics investigates intact naturally-occurring structure of a
protein under examination; bottom-up proteomics analyses peptide fragments after
pre-digestion (typically with trypsin). Because of this heterogeneity, many
different biomarkers may be proposed for the same pathology. The salivary
proteome has been characterised in several diseases: oral squamous cell carcinoma
and oral leukoplakia, chronic graft-versus-host disease Sjogren's syndrome and
other autoimmune disorders such as SAPHO, schizophrenia and bipolar disorder, and
genetic diseases like Down's Syndrome and Wilson disease. The results of research
reported herein suggest that in the near future human saliva will be a relevant
diagnostic fluid for clinical diagnosis and prognosis.
PMID- 28516972
TI - Sialendoscopy for salivary stones: principles, technical skills and therapeutic
experience.
AB - Obstructive sialadenitis is the most common non-neoplastic disease of the
salivary glands, and sialendoscopy is increasingly used in both diagnosis and
treatment, associated in selected cases with endoscopic laser lithotripsy.
Sialendoscopy is also used for combined minimally invasive external and
endoscopic approaches in patients with larger and proximal stones that would
require excessively long laser procedures. The present paper reports on the
technical experience from the Ear, Nose and Throat Unit of the Sant'Orsola
Malpighi Hospital of Bologna, and from the Department of Otorhinolaryngology of
the University Hospital of Cagliari, Italy, including the retrospective analysis
of the endoscopic and endoscopic assisted procedures performed on 48 patients (26
females and 22 males; median age 45.3; range 8-83 years) treated for chronic
obstructive sialadenitis at the University Hospital of Cagliari from November
2010 to April 2016. The results from the Sant'Orsola-Malpighi Hospital of Bologna
have been previously published. The technical aspects of sialendoscopy are
carefully described. The retrospective analysis of the University Hospital of
Cagliari shows that the disease was unilateral in 40 patients and bilateral in 8;
a total of 56 major salivary glands were treated (22 submandibular glands and 34
parotids). Five patients underwent bilateral sialendoscopy for juvenile recurrent
parotitis. 10 patients were treated for non-lithiasic obstructive disease. In 33
patients (68.75%) the obstruction was caused by salivary stones (bilateral
parotid lithiasis in 1 case). Only 8 patients needed a sialectomy (5
submandibular glands and 3 parotids). The conservative approach to obstructive
sialadenitis is feasible and can be performed either purely endoscopically or in
a combined modality, with a high percentage of success. The procedure must be
performed with dedicated instrumentation by a skilled surgeon after proper
training since minor to major complications can be encountered. Sialectomy should
be the "extrema ratio" after failure of a conservative approach.
PMID- 28516974
TI - Sialendoscope-assisted transoral removal of hilo-parenchymal sub-mandibular
stones: surgical results and subjective scores.
AB - It has been suggested that a conservative trans-oral approach to proximal and
hilo-parenchymal submandibular stones (HPSMS) is a valid alternative to the more
frequently used sialadenectomy. The aim of this study was to evaluate the
surgical, ultrasonographic and patients' subjective outcomes of results of the
trans-oral removal of HPSMS. Between January 2003 and September 2015,
sialendoscope-assisted trans-oral surgery was used to remove symptomatic, large
(> 7 mm), fixed and palpable HPSMS from 479 patients under general anaesthesia.
All patients were followed clinically and ultrasonographically to investigate
symptom relief and recurrence of stones, and were telephonically interviewed to
assess saliva-related subjective outcomes with a questionnaire. Stones were
successfully removed from 472 patients (98.5%); the seven failures (1.5%)
concerned pure parenchymal stones. One year after the procedure, 408 patients
(85.1%) were symptom free, 59 (12.3%) had recurrent obstructive symptoms and 12
(2.6%) had recurrent infections. Of the 54 patients who developed a recurrent
stone (11.2%), 52 underwent a second procedure: 29 interventional
sialendoscopies, two sialendoscope-assisted intra-corporeal pneumatic
lithotripsy, eight secondary transoral surgery to remove residual stones, six a
cycle of extra-corporeal lithotripsy and seven submandibular sialadenectomy. Most
patients (75.2%) reported mild surgery-related pain. The symptoms of 454 patients
(94.8%) improved after adjunctive treatment and, at the end of follow-up, the
affected gland was preserved in 98.5% of patients. A sialendoscope-assisted trans
oral removal of large HPSMS is a safe, effective, conservative surgical
procedure, and functional preservation of the main duct and parenchyma of the
obstructed gland allows sialendoscopic access through the natural ostium in case
of recurrence. Combining a trans-oral approach with other minimally invasive,
conservative procedures ensures symptomatic relief and salivary duct system
clearance in the majority of patients.
PMID- 28516973
TI - Salivary lithotripsy in the era of sialendoscopy.
AB - The traditional management of obstructive salivary disorders has been replaced by
minimally-invasive gland-preserving techniques including shock-wave lithotripsy,
sialendoscopy, interventional radiology and endoscopically video-assisted trans
oral and cervical stone retrieval, of which sialendoscopy is considered to be the
method of first choice. Primary endoscopically controlled stone extraction
without prior fragmentation is only possible in 15-20% of cases; in more than
80%, fragmentation is necessary because of the size, impactation and location of
the stone, or an alternative treatment such as transoral duct surgery or combined
approaches are required. Moreover, about 10-20% of all stones cannot be
adequately accessed by means of a sialendoscope or any alternative surgical
method and, in such cases, extra-corporeal shock wave lithotripsy (ESWL) is the
treatment of choice. However, in endoscopically accessible stones, ESWL is being
gradually replaced by endoscopically assisted intra-corporeal techniques,
including endoscopically guided laser and pneumatic intracorporeal lithotripsy.
We describe the currently most widely used techniques for salivary lithotripsy,
including ESWL, and endoscopically guided laser, electrohydraulic, electrokinetic
and pneumatic intra-corporeal lithotripsy, and discuss their indications given
the widespread use of advanced rehabilitative sialendoscopy and combined
therapeutic approaches.
PMID- 28516975
TI - Sialendoscopy-assisted transfacial removal of parotid calculi.
AB - Superficial parotidectomy has significant morbidity, and minimally invasive
techniques have therefore been developed, including those involving
sialendoscopy, to remove sialoliths and preserve the gland along with its
function. The size, mobility and location of the sialolith, alongside the
presence of strictures, all dictate management. We outline basic treatment
paradigms and describe two sialoendoscopyassisted surgical procedures developed
for treating stones, one intraoral and one extraoral.
PMID- 28516976
TI - Salivary duct stenosis: diagnosis and treatment.
AB - The management of stenoses of the major salivary glands had undergone a
significant change during the last 15-20 years. Accurate diagnosis forms the
basis of adapted minimal invasive therapy. Conventional sialography and MR
sialography are useful examination tools, and ultrasound seems to be a first-line
investigational tool if salivary duct stenosis is suspected as cause of gland
obstruction. Sialendoscopy is the best choice to establish final diagnosis and
characterise the stenosis in order to plan accurate treatment. In all major
salivary glands, inflammatory stenosis can be distinguished from fibrotic
stenosis. In the parotid duct system, an additional stenosis associated with
various abnormalities of the duct system has been reported. Conservative therapy
is not sufficient in the majority of cases. The development of a minimally
invasive treatment regime, in which sialendoscopy plays a major role, has made
the preservation of the gland and its function possible in over 90% of cases.
Ductal incision procedures are the most important measure in submandibular duct
stenoses, but sialendoscopy becomes more important in the more centrally located
stenoses. Sialendoscopic controlled opening and dilation is the dominating method
in parotid duct stenoses. In 10-15% of cases, success can be achieved after a
combined treatment regime had been applied. This review article aims to give an
overview on the epidemiology, diagnostics and current state of the art of the
treatment of salivary duct stenoses.
PMID- 28516977
TI - Complications of traditional and modern therapeutic salivary approaches.
AB - The morbidity following traditional surgery of the salivary glands is well
documented and includes postsurgical complications such as the Frey's syndrome,
complete or partial facial nerve damage, facial scarring, greater auricular nerve
numbness, sialocoeles and salivary fistula. The avulsion of the salivary duct,
secondary strictures, gland swelling, salivary fistulas and perforations (false
rout), traumatic ranulas, and the lingual nerve paraesthesia are the main
endoscopy-related complications. In general, the rate of postsurgical
complications after modern advanced minimally invasive surgical interventions is
significantly lower compared with traditional surgery of the salivary glands.
However, such comparisons cannot be performed because up-to-date traditional and
minimally invasive surgical techniques are applied to different salivary
disorders. Combinations of various minimally invasive techniques are also
possible. There is no clear borderline between "traditional" and "modern" surgery
of the salivary glands. It is appropriate to write about gradual replacement of
old techniques with newer ones, and this process has no traffic lights.
PMID- 28516979
TI - Interventional sialendoscopy for radioiodine-induced sialadenitis: quo vadis?
AB - Salivary gland toxicity is a common adverse effect of radioactive iodine (131I)
for the treatment of thyroid cancers with a prevalence ranging from 2% to 67% of
the 131I exposed population. Recently, sialendoscopy has been introduced as an
attractive diagnostic and therapeutic tool for management of patients with
radioiodine-induced sialadenitis that is unresponsive to standard medical
treatments. The objective of the current review was to assess the impact of this
procedure on outcomes in patients suffering from radioiodine sialadenitis.
Overall, eight studies were included and 122 patients underwent 264
sialendoscopic procedures. Duct stenosis and mucous plugs were observed in 85.7%
of endoscopic findings, supporting the role of ductal obstruction in the
pathophysiology of radioiodine sialadenitis. In total, 89.3% of patients
experienced complete or partial resolution of sialadenitis recurrences without
any major adverse events, and parotidectomy was advocated in only 1 case.
However, outcomes mainly concerned subjective reports and only two clinical
experiences evaluated objective measurement with dissimilar results. Limited to
few studies, xerostomia and obstructive symptoms responded differently after
sialendoscopy. The optimal timing of salivary gland videoendoscopy needs to be
further analysed in order to define the best management of radioiodine-induced
obstructive sialadenitis.
PMID- 28516978
TI - Sialendoscopic management of autoimmune sialadenitis: a review of literature.
AB - Autoimmune diseases of major salivary glands include Sjogren's syndrome and a
complex of disorders classified as immunoglobulin G4-related diseases. These
pathologies are characterised by an autoimmune reaction mediated by T-helper
lymphocytes that targets the ducts of exocrine glands in Sjogren's syndrome and
glandular parenchyma in immunoglobulin G4-related diseases. Immunoglobulin G4
related diseases represent recently introduced multi-organ diseases that also
involve the salivary glands. However, the morbid conditions once known as
Mikulicz's disease and Kuttner's tumour were recently considered as two variants
of immunoglobulin G4-related diseases affecting the major salivary glands (
immunoglobulin G4-related sialadenitis). This review briefly summarises the
pathogenesis and clinical features of autoimmune diseases of the major salivary
glands, focusing on the diagnostic and therapeutic role of sialendoscopy.
PMID- 28516980
TI - Modern management of paediatric obstructive salivary disorders: long-term
clinical experience.
AB - Recent technological improvements in head and neck field have changed diagnostic
and therapeutic strategies for salivary disorders. Diagnosis is now based on
colour Doppler ultrasonography (US), magnetic resonance (MR) sialography and cone
beam 3D computed tomography (CT), and extra- and intracorporeal lithotripsy,
interventional sialendscopy and sialendoscopy-assisted surgery are used as
minimally invasive, conservative procedures for functional preservation of the
affected gland. We evaluated the results of our long-term experience in the
management of paediatric obstructive salivary disorders. The study involved a
consecutive series of 66 children (38 females) whose obstructive salivary
symptoms caused by juvenile recurrent parotitis (JRP) (n = 32), stones (n = 20),
ranula (n = 9) and ductal stenosis (n = 5). 45 patients underwent interventional
sialendoscopy for JRP, stones and stenoses, 12 a cycle of extracorporeal
shockwave lithotripsy (ESWL), three sialendoscopy-assisted transoral surgery, one
drainage, six marsupialisation, and two suturing of a ranula. Three children
underwent combined ESWL and interventional sialendoscopy, and seven a secondary
procedure. An overall successful result was obtained in 90.9% of cases. None of
the patients underwent traditional invasive sialadenectomy notwithstanding
persistence of mild obstructive symptoms in six patients. No major complications
were observed. Using a diagnostic work-up based on colour Doppler US, MR
sialography and cone beam 3D TC, children with obstructive salivary disorders can
be effectively treated in a modern minimally-invasive manner by extracorporeal
and intracorporeal lithotripsy, interventional sialendoscopy and sialendoscopy
assisted transoral surgery; this approach guarantees a successful result in most
patients, thus avoiding the need for invasive sialadenectomy while functionally
preserving the gland.
PMID- 28516982
TI - Colorimetric and electrochemical quantification of global DNA methylation using a
methyl cytosine-specific antibody.
AB - We report a simple colorimetric (naked-eye) and electrochemical method for the
rapid, sensitive and specific quantification of global methylation levels using
only 25 ng of input DNA. Our approach utilises a three-step strategy; (i) initial
adsorption of the extracted, purified and denatured bisulfite-treated DNA on a
screen-printed gold electrode (SPE-Au), (ii) immuno-recognition of methylated DNA
using a horseradish peroxidase (HRP)-conjugated methylcytosine (HRP-5mC) antibody
and (iii) subsequent colorimetric detection by the enzymatic oxidation of
3,3',5,5'-tetramethylbenzidin (TMB)/H2O2 which generated a blue-coloured product
in the presence of methylated DNA and HRP-5mC immunocomplex. As TMB(ox) is
electroactive, it also produces detectable amperometric current at +150 mV versus
a Ag pseudo-reference electrode (electrochemical detection). The assay could
successfully differentiate 5-aza-2'-deoxycytidine drug-treated and untreated
Jurkat DNA samples. It showed good reproducibility (relative standard deviation
(% RSD) = <5%, for n = 3) with fairly good sensitivity (as low as 5% difference
in methylation levels) and specificity while analysing various levels of global
DNA methylation in synthetic samples and cell lines. The method has also been
tested for analysing the methylation level in fresh tissue samples collected from
eight patients with oesophageal squamous cell carcinoma. We believe that this
assay could be potentially useful as a low-cost alternative for genome-wide DNA
methylation analysis in point-of-care applications.
PMID- 28516981
TI - Botulinum toxin therapy: functional silencing of salivary disorders.
AB - Botulinum toxin (BTX) is a neurotoxic protein produced by Clostridium botulinum,
an anaerobic bacterium. BTX therapy is a safe and effective treatment when used
for functional silencing of the salivary glands in disorders such as sialoceles
and salivary fistulae that may have a post-traumatic or post-operative origin.
BTX injections can be considered in sialoceles and salivary fistulae after the
failure of or together with conservative treatments (e.g. antibiotics, pressure
dressings, or serial aspirations). BTX treatment has a promising role in chronic
sialadenitis. BTX therapy is highly successful in the treatment of gustatory
sweating (Frey's syndrome), and could be considered the gold standard treatment
for this neurological disorder.
PMID- 28516985
TI - Gate-controlled heat generation in ZnO nanowire FETs.
AB - Nanoscale heating production using nanowires has been shown to be particularly
attractive for a number of applications including nanostructure growth, localized
doping, transparent heating and sensing. However, all proof-of-concept devices
proposed so far relied on the use of highly conductive nanomaterials, typically
metals or highly doped semiconductors. In this article, we demonstrate a novel
nanoheater architecture based on a single semiconductor nanowire field-effect
transistor (NW-FET). Nominally undoped ZnO nanowires were incorporated into three
terminal devices whereby control of the nanowire temperature at a given source
drain bias was achieved by additional charge carriers capacitatively induced via
the third gate electrode. Joule-heating selective ablation of poly(methyl
methacrylate) deposited on ZnO nanowires was shown, demonstrating the ability of
the proposed NW-FET configuration to enhance by more than one order of magnitude
the temperature of a ZnO nanowire, compared to traditional two-terminal
configurations. These findings demonstrate the potential of field-effect
architectures to improve Joule heating power in nanowires, thus vastly expanding
the range of suitable materials and applications for nanowire-based nanoheaters.
PMID- 28516984
TI - Cadmium transfer from contaminated soils to the human body through rice
consumption in southern Jiangsu Province, China.
AB - Consumption of crops grown in cadmium-contaminated soils is an important Cd
exposure route to humans. The present study utilizes statistical analysis and in
vitro digestion experiments to uncover the transfer processes of Cd from soils to
the human body through rice consumption. Here, a model was created to predict the
levels of bioaccessible Cd in rice grains using phytoavailable Cd quantities in
the soil. During the in vitro digestion, a relatively constant ratio between the
total and bioaccessible Cd in rice was observed. About 14.89% of Cd in soils was
found to be transferred into rice grains and up to 3.19% could be transferred
from rice grains to the human body. This model was able to sufficiently predict
rice grain cadmium concentrations based on CaCl2 extracted zinc and cadmium
concentrations in soils (R2 = 0.862). The bioaccessible Cd concentration in rice
grains was also able to be predicted using CaCl2 extracted cadmium from soil (R2
= 0.892). The models established in this study demonstrated that CaCl2 is a
suitable indicator of total rice Cd concentrations and bioaccessible rice grain
Cd concentrations. The chain model approach proposed in this study can be used
for the fast and accurate evaluation of human Cd exposure through rice
consumption based on the soil conditions in contaminated regions.
PMID- 28516986
TI - Single-layer MoS2 formation by sulfidation of molybdenum oxides in different
oxidation states on Au(111).
AB - The sulfidation of a MoO3 precursor into MoS2 is an important step in the
preparation of catalysts for the hydrodesulfurization process that is widely
utilized in oil refineries. Molybdenum oxides are also the most commonly used
precursors for MoS2 growth in, e.g., the synthesis of novel two-dimensional
materials. In the present study, we investigate the transformation of MoOx into
MoS2 on a model Au(111) surface through sulfidation in H2S gas atmosphere using
in situ scanning tunneling microscopy and X-ray photoemission spectroscopy. We
find that progressive annealing steps of physical vapor deposited MoO3 powder
allow us to control the stoichiometry and oxidation state of the precursor oxide.
Subsequently, we investigate the sulfidation of the compounds ranging from pure
low-oxygen Mo to fully oxidized MoO3 oxide sulfidation using two different
methods. We find that the prerequisite for the efficient formation of MoS2 is
that Mo stays in the highest Mo6+ state before sulfidation, whereas the presence
of the reduced MoOx phase impedes the MoS2 growth. We also find that it is more
efficient to form MoS2 by post-sulfidation of MoOx rather than its reactive
deposition in H2S gas, which leads to rather stable amorphous oxysulfide phases.
PMID- 28516987
TI - Theoretical investigations into the charge transfer properties of thiophene alpha
substituted naphthodithiophene diimides: excellent n-channel and ambipolar
organic semiconductors.
AB - A theoretical study was carried out to investigate the electronic structures and
the charge transport properties of a series of naphthodithiophene diimide (NDTI)
thiophene alpha-substituted derivatives NDTI-X using density functional theory
and classical Marcus charge transfer theory. This study deeply revealed the
structure-property relationships by analyzing the intermolecular interactions in
crystal structures of C8-NDTI and C8-NDTI-Cl thoroughly by using the Hirshfeld
surface, QTAIM theories and symmetry-adapted perturbation theory (SAPT). Our
results suggested that a 2-D brick-like pi-stacking structure makes C8-NDTI-Cl a
more excellent n-type semiconducting material with MUmax-e of 2.554 cm2 V-1 s-1
than C8-NDTI with a herringbone-like slipped pi-stacking motif. In addition, the
calculated results showed that by modifying the thiophene alpha-positions of NDTI
with electron-withdrawing substituents, -F, -Cl and -CN, low-lying LUMO energy
levels and a high adiabatic electron affinity EA(a) can be obtained; while
introducing electron-donating groups, benzene (-B), thiophene (-T),
benzo[b]thiophene (-BT) and naphtha[2,3-b]thiophene (-NT), expanded the molecular
pi-conjugated backbone, and narrow band gaps, high EA(a) and small reorganization
energies can be obtained. Theoretical simulations predict that NDTI-CN is an
excellent air-stable n-type organic semiconducting material with an average
electron mobility MUe of up to 1.743 cm2 V-1 s-1. Owing to their high EA(a),
moderate adiabatic ionization potential IP(a) as well as small hole and electron
reorganization energies, NDTI-BT and NDTI-NT are two well-balanced air-stable
ambipolar semiconducting materials. The theoretical average hole/electron
mobilities are as high as 2.708/3.739 cm2 V-1 s-1 for C8-NDTI-NT and 1.597/2.350
cm2 V-1 s-1 for C8-NDTI-BT, respectively.
PMID- 28516989
TI - The effect of anions on the electrochemical properties of polyaniline for
supercapacitors.
AB - To investigate the effect of anions on the electrochemical properties of
polyaniline (PANI) for supercapacitors, electrochemical performance tests of PANI
with different dopant anions were carried out in the corresponding acid solutions
by cyclic voltammetry (CV) and galvanostatic charge-discharge (GCD) methods. In
particular, ionic fluxes and solvent molecules involved in redox processes can be
analyzed by the electrochemical quartz crystal microbalance (EQCM) technique and
discriminated by simultaneously recording cyclic voltammograms and mass changes
during redox switching. The emeraldine base (EB) form of PANI prepared in a
protonic acid with bigger anions can be easily doped by a protonic acid with
smaller anions, and conversely, PANI-EB is hard to be doped. The anodic reversal
potential of potentiodynamic cycling heavily influences the electrochemical
stability of PANI. High anodic potentials result in PANI degradation. Its
supercapacitive properties including specific capacitance, power density and
cycling stability are strongly dependent upon the type of dopant anion. PANI with
the dopant anions of oxalic acid has the highest specific capacitance and the
best cycling stability among the used acids. The diffusion coefficient of anions
plays a key role in determining power density. PANI films with organic dopant
anions exhibit better cycling stability than their inorganic counterparts. It is
believed that the hydrolysis of PANI facilitated by the additional water
molecules accompanied by dopant anions into and out of the PANI matrix is a key
factor responsible for the cycling instability.
PMID- 28516988
TI - Syntheses and catalytic oxotransfer activities of oxo molybdenum(vi) complexes of
a new aminoalcohol phenolate ligand.
AB - The new aminoalcohol phenol 2,4-di-tert-butyl-6-(((2-hydroxy-2
phenylethyl)amino)methyl)phenol (H2L) was prepared by a facile solvent-free
synthesis and used as a tridentate ligand for new cis-dioxomolybdenum(vi)(L)
complexes. In the presence of a coordinating solvent (DMSO, MeOH, pyridine), the
complexes crystallise as monomeric solvent adducts while in the absence of such
molecules, a trimer with asymmetric Mo[double bond, length as m-dash]O->Mo
bridges crystallises. The complexes can catalyse epoxidation of cis-cyclooctene
and sulfoxidation of methyl-p-tolylsulfide, using tert-butyl hydroperoxide as
oxidant.
PMID- 28516990
TI - Cross talk between neurometals and amyloidogenic proteins at the synapse and the
pathogenesis of neurodegenerative diseases.
AB - Increasing evidence suggests that disruption of metal homeostasis contributes to
the pathogenesis of various neurodegenerative diseases, including Alzheimer's
disease, prion diseases, Lewy body diseases, and vascular dementia.
Conformational changes of disease-related proteins (amyloidogenic proteins), such
as beta-amyloid protein, prion proteins, and alpha-synuclein, are well
established contributors to neurotoxicity and to the pathogenesis of these
diseases. Recent studies have demonstrated that these amyloidogenic proteins are
metalloproteins that bind trace elements, including zinc, iron, copper, and
manganese, and play significant roles in the maintenance of metal homeostasis. We
present a current review of the role of trace elements in the functions and
toxicity of amyloidogenic proteins, and propose a hypothesis integrating metal
homeostasis and the pathogenesis of neurodegenerative diseases that is focused on
the interactions among metals and between metals and amyloidogenic proteins at
the synapse, considering that these amyloidogenic proteins and metals are co
localized at the synapse.
PMID- 28516992
TI - A nano silver-xerogel (Ag nps@modified TEOS) as a newly developed nanocatalyst in
the synthesis of benzopyranopyrimidines (with secondary and primary amines) and
gem-bisamides.
AB - Silver nanoparticles have been prepared from a chemical reduction approach and
supported on modified TEOS (tetraethylorthosilicate) xerogels to be studied as a
nanocatalyst in the conversions of benzopyranopyrimidines (with primary as well
as secondary amines along with the mechanism by trapping the imine intermediate)
and also in the synthesis of gem-bisamides. Different conditions for the
performance of the nanocatalyst have been screened and tolerance with respect to
variable functionalities has been observed, resulting in excellent yields; and
confirmation of products synthesized has been done using studies like 1H NMR, 13C
NMR and mass analysis. Also, SEM-EDX and TEM of the nanocatalyst have been
performed to know the internal and external morphology, size and elemental
composition. UV and XRD analysis to confirm the silver nanoparticles' and
xerogel's presence, TGA to study the thermal stability and FTIR to study the
modification pattern of the nanocatalyst have been undertaken and presented in
this work.
PMID- 28516991
TI - Synthesis, properties, and crystal structures of pi-extended double [6]helicenes:
contorted multi-dimensional stacking lattice.
AB - The synthesis and properties of a new pi-extended double [6]helicene 2 and a
dithia[6]helicene 3 are described. Compared to the previously reported parent
double-helicene molecule 1, the introduction of n-butyl groups successfully
improved the solubility, which allowed an experimental investigation into the
electronic structure of 2 and 3 by photophysical measurements and cyclic
voltammetry. The characteristic two-blade propeller structures of 2 and 3 were
unambiguously determined by single-crystal X-ray diffraction analysis. The
crystal packing structure of 2 exhibited a contorted two-dimensional stacking,
whereby molecules of n-pentane were incorporated in the stacks. Despite the
presence of n-butyl groups, 3 formed a unique three-dimensional stacking lattice
in the crystal. Time-resolved microwave conductivity measurements revealed that
the double helicenes (1-3) exhibited transient conductivities. An organic field
effect transistor fabricated using 3 was found to function as a p-type
transistor.
PMID- 28516993
TI - Stable and conductive lead halide perovskites facilitated by X-type ligands.
AB - Lead halide perovskites exhibit outstanding optoelectronic and optical
properties. However, some applications of perovskites are hindered by their
instability in polar environments; thus, how to balance stability with
conductivity is a great challenge. Here, we report a new approach of using X-type
ligands to address this issue. Surface treatments containing multi-step ligand
exchanges and ion filling were necessary to obtain X-type ligand-protected
perovskites. Performances of this material show that: (1) the crystal structure
of perovskites is stable in ethanol; (2) surface defects can be fixed by a
photoactivation process and photoluminescence intensity can be enhanced to 136%;
and (3) electronic devices fabricated from such materials show stabilility even
after washing with ethanol. X-type ligand-protected perovskites with high
stability and good conductivity are promising new materials for wide applications
in electronic and optoelectronics devices.
PMID- 28516983
TI - Nanoparticle design strategies for enhanced anticancer therapy by exploiting the
tumour microenvironment.
AB - Nanovehicles can efficiently carry and deliver anticancer agents to tumour sites.
Compared with normal tissue, the tumour microenvironment has some unique
properties, such as vascular abnormalities, hypoxia and acidic pH. There are many
types of cells, including tumour cells, macrophages, immune and fibroblast cells,
fed by defective blood vessels in the solid tumour. Exploiting the tumour
microenvironment can benefit the design of nanoparticles for enhanced therapeutic
effectiveness. In this review article, we summarized the recent progress in
various nanoformulations for cancer therapy, with a special emphasis on tumour
microenvironment stimuli-responsive ones. Numerous tumour microenvironment
modulation strategies with promising cancer therapeutic efficacy have also been
highlighted. Future challenges and opportunities of design consideration are also
discussed in detail. We believe that these tumour microenvironment modulation
strategies offer a good chance for the practical translation of nanoparticle
formulas into clinic.
PMID- 28516994
TI - 3D ordered porous MoxC (x = 1 or 2) for advanced hydrogen evolution and Li
storage.
AB - 3D ordered porous structures of MoxC are prepared with different Mo to C ratios
and tested for two possible promising applications: hydrogen evolution reaction
(HER) through water splitting and lithium ion batteries (LIBs). Mo2C and MoC with
3D periodic ordered structures are prepared with a similar process but different
precursors. The 3D ordered porous MoC exhibits excellent cycling stability and
rate performance as an anode material for LIBs. A discharge capacity of 450.9 mA
h g-1 is maintained up to 3000 cycles at 10.0 A g-1. The Mo2C with a similar
ordered porous structure shows impressive electrocatalytic activity for the HER
in neutral, alkaline and acidic pH solutions. In particular, Mo2C shows an onset
potential of only 33 mV versus a reversible hydrogen electrode (RHE) and a Tafel
slope of 42.5 mV dec-1 in a neutral aqueous solution (1.0 M phosphate buffer
solution), which is approaching that of the commercial Pt/C catalyst.
PMID- 28516995
TI - Regioselective 6-endo-dig iodocyclization: an accessible approach for iodo
benzo[a]phenazines.
AB - A facile approach for the synthesis of substituted iodo-benzo[a]phenazines from 2
aryl-3-(aryl/alkylethynyl)quinoxalines via 6-endo-dig ring closure has been
described under mild reaction conditions. Iodocyclization proceeds through the
iodonium ion intermediate followed by nucleophilic cyclization with the C-H bond
of the arene. Furthermore, the resulting 6-iodo-5-aryl/alkyl benzo[a]phenazine
derivatives allowed for structural diversification by employing various coupling
reactions. The structure of iodo-benzo[a]phenazine was confirmed by X-ray
crystallographic studies of the compound.
PMID- 28516996
TI - Growth of two dimensional silica and aluminosilicate bilayers on Pd(111): from
incommensurate to commensurate crystalline.
AB - Two-dimensional (2D) silica (SiO2) and aluminosilicate (AlSi3O8) bilayers grown
on Pd(111) were fabricated and systematically studied using ultrahigh vacuum
surface analysis in combination with theoretical methods, including Auger
electron spectroscopy, X-ray photoelectron spectroscopy, low-energy electron
diffraction (LEED), scanning tunneling microscopy (STM), and density functional
theory. Based on LEED results, both SiO2 and AlSi3O8 bilayers start ordering
above 850 K in 2 * 10-6 Torr oxygen. Both bilayers show hexagonal LEED patterns
with a periodicity approximately twice that of the Pd(111) surface. Importantly,
the SiO2 bilayer forms an incommensurate crystalline structure whereas the
AlSi3O8 bilayer crystallizes in a commensurate structure. The incommensurate
crystalline SiO2 structure on Pd(111) resulted in a moire pattern observed with
LEED and STM. Theoretical results show that straining the pure SiO2 bilayer to
match Pd(111) would cost 0.492 eV per unit cell; this strain energy is reduced to
just 0.126 eV per unit cell by replacing 25% of the Si with Al which softens the
material and expands the unstrained lattice. Furthermore, the missing electron
created by substituting Al3+ for Si4+ is supplied by Pd creating a chemical bond
to the AlSi3O8 bilayer, whereas van der Waals interactions predominate for the
SiO2 bilayer. The results reveal how the interplay between strain, doping, and
charge transfer determine the structure of metal-supported 2D silicate bilayers
and how these variables may potentially be exploited to manipulate 2D materials
structures.
PMID- 28516998
TI - Controllable design of tunable nanostructures inside metal-organic frameworks.
AB - The controllable encapsulation of nanoentities (such as metal nanoparticles,
quantum dots, polyoxometalates, organic and metallorganic molecules,
biomacromolecules, and metal-organic polyhedra) into metal-organic frameworks
(MOFs) to form composite materials has attracted significant research interest in
a variety of fields. These composite materials not only exhibit the properties of
both the nanoentities and the MOFs but also display unique and synergistic
functionalities. Tuning the sizes, compositions, and shapes of nanoentities
encapsulated in MOFs enables the final composites to exhibit superior performance
to those of the separate constituents for various applications. In this tutorial
review article, we summarized the state-of-the-art development of MOFs containing
encapsulated tunable nanoentities, with special emphasis on the preparation and
synergistic properties of these composites.
PMID- 28517001
TI - Gold-catalyzed oxidative hydroacylation reactions of alpha-iminoalkynes with
aldehydes and O2.
AB - Gold-catalyzed aerobic oxidations of alpha-iminoalkynes with aryl aldehydes led
to oxidative 1,3-hydroacyclation reactions, yielding high Z-selectivity. We
performed 2H- and 18O-labeling experiments to confirm the role of water as an
oxygen donor and O2 as the main oxidant. The Z-selectivity arises from an
efficient conjugation between the enone and its aryl substituent. We postulate an
initial [4+2]-annulation of alpha-iminoalkynes with aldehydes to form a six
membered oxonium species that is attacked by water, followed by the O2 oxidation
of a key intermediate.
PMID- 28516997
TI - Peptide and antibody ligands for renal targeting: nanomedicine strategies for
kidney disease.
AB - The kidney is one of the body's main filtration organs, and hence, opportunity
exists for designing nanomedicine that can naturally accumulate in the kidneys
for renal diseases. In addition to traditional physiochemical properties for
kidney accumulation, such as size and charge, synthesized nanoparticles can be
conjugated with targeting ligands which further home the nanocarriers to cell
types of interest. In this review, we highlight key studies that have shown
success in utilizing peptide- or antibody-based ligands in nanoparticles to
target the glomerulus, podocytes, or renal tubule cells in the kidney. In
addition, other ligand candidates which have shown renal affinity, but have not
yet been integrated into a nanoparticle are also presented. These studies can
provide insight into the design of novel clinical solutions for improved
detection, prevention, and treatment of renal diseases using nanomedicine
efforts.
PMID- 28517002
TI - Modulation of the FeII spin crossover effect in the pentadecanuclear
{Fe9[M(CN)8]6} (M = Re, W) clusters by facial coordination of tridentate
polyamine ligands.
AB - Spin crossover (SCO) materials, revealing the externally tunable transition
between two different spin states, arouse great scientific interest due to their
perspective application in information storage, display devices and sensing. Of
special importance are the molecular systems offering the possibility of
multimodal switching within many spin centers. This is achievable in polynuclear
clusters consisting of several SCO-active complexes, however, such molecules are
very rare. Herein, we report a unique pair of nanometric pentadecanuclear
{Fe9[M(CN)8]6(Me3tacn)8}.14MeOH (Me3tacn = 1,4,7-trimethyl-1,4,7
triazacyclononane, M = Re, 1; M = W, 2) clusters exhibiting a thermally induced
spin crossover effect on Fe(ii) complexes, that is on both central and external
Fe sites embedded in the cyanido-bridged cluster core. The spin transition occurs
gradually in the 120-300 K range, and it is not fully completed even at room
temperature. We show that facial coordination of an N,N,N-tridentate Me3tacn
ligand dramatically modifies the character of the spin transition phenomenon when
confronted with the previously reported {Fe9[M(CN)8]6(MeOH)24}.nMeOH (M = Re, W)
clusters by (i) engaging, for the first time, not only central but also external
Fe intracluster units in the SCO effect, (ii) cancelling the Fe-W charge transfer
pathway, and (iii) decreasing the cooperativity within the supramolecular
network.
PMID- 28517003
TI - Liquid phase epitaxial growth of heterostructured hierarchical MOF thin films.
AB - Precise control of epitaxial growth of MOF-on-MOF thin films, for ordered
hierarchical tbo-type structures is demonstrated. The heterostructured MOF thin
film was fabricated by successful sequential deposition of layers from two
different MOFs. The 2-periodic layers, edge-transitive 4,4-square lattices
regarded as supermolecular building layers, were commendably cross-linked using a
combination of inorganic/organic and organic pillars.
PMID- 28517004
TI - Exploitation of new structurally diverse d-glucuronamide-containing N-glycosyl
compounds: synthesis and anticancer potential.
AB - The synthesis and anticancer evaluation of novel N-glycosyl derivatives
containing N-substituted glucuronamide moieties, as nucleoside analogs or as
prospective mimetics of glycosyl phosphates or of nucleotides, is reported. These
compounds comprise N-anomerically-linked nucleobases or motifs that are
surrogates of a phosphate group, such as sulfonamide or phosphoramidate moieties.
1-Sulfonamido glucuronamides containing N-benzyl, N-propargyl or N-dodecyl
carboxamide units were synthesized through glycosylation of methanesulfonamide
with tetra-O-acetyl glucuronamides. 1-Azido glucuronamides were accessed by
microwave-assisted reactions of tetra-O-acetyl glucuronamides with TMSN3 and were
further converted into N-glycosylphosphoramidates by treatment with trimethyl
phosphite. Potential glucuronamide-based nucleotide mimetics comprising both an
anomeric sulfonamide/phosphoramidate group and a benzyltriazolylmethyl amide
system at C-5, as nucleobase mimetics, were synthesized via 'click' cycloaddition
of N-propargyl glucuronamide derivatives with benzyl azide. N-Dodecyl tetra-O
acetyl glucuronamides were converted into uracil and purine nucleosides via N
glycosylation of the corresponding silylated nucleobases. Biological screening
revealed significant antiproliferative activities of the N-dodecyl glucuronamide
containing sulfonamide, phosphoramidate and nucleosides in K562 and MCF-7 cells.
The highest effect was exhibited by the N9-linked purine nucleoside in the breast
cancer cell MCF-7 with a GI50 value similar to that of clinically used 5
fluorouracil. Immunoblotting and cell cycle analysis of K562 cells treated with
the most active compound as well as evaluation of the effect of this nucleoside
on the activities of caspases 3 and 7 showed induction of apoptosis as the
mechanism of cell death.
PMID- 28517005
TI - Hydrophobic hydration and anomalous diffusion of elastin in an ethanolic
solution.
AB - Elastin is an important structural protein that confers elasticity to tissues. It
is widely used in the biosynthesis of human elastic tissues and exhibits
interesting properties. This study reports an insight into the unusual dispersion
and anomalous diffusion of elastin in an ethanolic solution. Due to its complex
hydrophobic structure, its dispersibility was found to be sensitive towards the
hydrophobicity of the solvent. Electrophoresis measurements (zeta-potential data)
revealed that its net polarity changed from an anionic to a cationic state with
the decreasing solvent hydrophobicity (ethanol content in the solvent). An
interesting transition temperature of ~297 K was observed above which the
hydrophobic interactions among the protein molecules became dominant. Double
layer repulsion between protein molecules competes with attractive hydrophobic
interactions and causes molecular self-organization. A DLVO-based theoretical
model showed that hydrophobic interactions were facilitated by a binary solvent
(ethanol-water), and the repulsive double layer screening provided sufficient
energy to overcome the interactions between hydrophobic domains in the protein
molecule and allow the self-assembly to occur.
PMID- 28517006
TI - Synthesis and characterization of a family of thioether-dithiolate-bridged
heteronuclear iron complexes.
AB - The thioether-dithiolate-bridged heterotrinuclear complexes [Cp*Fe(MU
1k3SSS':2k2SS-tpdt)M(MU-2k2SS:3k3SSS'-tpdt)FeCp*][PF6]2 (Cp* = eta5-C5Me5; tpdt =
S(CH2CH2S)2; 2, M = Co; 3, M = Ni; 4, M = Pd) have been prepared by a reaction of
[Cp*Fe(eta3-tpdt)] (1) with complexes CoCl2, NiCl2(PPh3)2, and PdCl2(PPh3)2,
respectively. Similarly, treatment of complex 1 with CuCl(PPh3) or AgPF6 afforded
two heterotrinuclear complexes, [Cp*Fe(MU-1k3SSS':2k2SS-tpdt)M(MU-2k2SS:3k3SSS'
tpdt)FeCp*][PF6] (5, M = Cu; 6, M = Ag), while reaction of 1 with the complex
AuCl(PPh3) gave a heterobinuclear complex, [Cp*Fe(MU-1k3SSS':2k1S
tpdt)Au(PPh3)][PF6] (7). These complexes have been spectroscopically and
crystallographically characterized. An X-ray diffraction analysis showed that
complexes 2, 3, 5, and 6 feature a heterometal center binding four sulfur atoms
of two tpdt ligands with a cis orientation. However, in the Pd-containing complex
4, two tpdt ligands are arranged in a trans configuration. The MUeff data and EPR
results indicate that complexes 2, 4, 5, 6, and 7 are paramagnetic and only
complex 3 is diamagnetic. Electrochemical experiments on these heteronuclear
clusters were performed at room temperature. Discrepancy of the redox couples in
the CV plots of these complexes indicates different one-electron transfer
processes.
PMID- 28517007
TI - Generation of a cell-permeable cycloheptapeptidyl inhibitor against the peptidyl
prolyl isomerase Pin1.
AB - Cyclic peptides are capable of binding and modulating challenging drug targets
including protein-protein interactions. However, their lack of membrane
permeability prevents their application against intracellular targets. In this
study, we show that it is possible to design a cell-permeable and biologically
active cycloheptapeptide inhibitor against the intracellular enzyme peptidyl
prolyl isomerase Pin1 by integrating cell-penetrating and target-binding
sequences.
PMID- 28517008
TI - Further insights into the kinetics of thermal decomposition during continuous
cooling.
AB - Following the previous work (Phys. Chem. Chem. Phys., 2016, 18, 32021), this
study continues to investigate the intriguing phenomenon of thermal decomposition
during continuous cooling. The phenomenon can be detected and its kinetics can be
measured by means of thermogravimetric analysis (TGA). The kinetics of the
thermal decomposition of ammonium nitrate (NH4NO3), nickel oxalate (NiC2O4), and
lithium sulfate monohydrate (Li2SO4.H2O) have been measured upon heating and
cooling and analyzed by means of the isoconversional methodology. The results
have confirmed the hypothesis that the respective kinetics should be similar for
single-step processes (NH4NO3 decomposition) but different for multi-step ones
(NiC2O4 decomposition and Li2SO4.H2O dehydration). It has been discovered that
the differences in the kinetics can be either quantitative or qualitative.
Physical insights into the nature of the differences have been proposed.
PMID- 28517009
TI - Stress-induced surface instabilities and defects in thin films sputter deposited
on compliant substrates.
AB - Existing analyses predict that thin metal films deposited on compliant substrates
are subject to a variety of surface instabilities, such as wrinkles, folds,
creases, etc., that become more prominent with increased compressive residual
stress. Under compressive stress, cracks have been assumed to form only when the
interfacial strength is weak, allowing the film to detach from the substrate. In
this work, we demonstrate that cracks also form on surfaces under compressive
mismatch strain when the interface is strong. In particular, we consider metal
alloy films sputter deposited under bias on elastomers with different
thicknesses, curing temperatures or surface treatments. The deposition parameters
created residual compressive strains and strong adhesion in the bilayers. Samples
without surface treatment formed wrinkles and through-thickness cracks at 0.25
0.4% mismatch strains. Only through-thickness cracks were observed in UV treated
samples. The crack spacing was found to decrease by a factor of 4 when the
surface was UV treated and by a factor of 3 as the elastomer thickness decreased
from 30 to 6 MUm. Cracks penetrated through the elastomer, 15-30 times deeper
than the film thickness, and formed in all samples with a brittle coating. A
numerical model was developed to explain the formation of through-thickness
cracks and wrinkles under applied compressive mismatch strains. The model
suggests that cracks can initiate from the peak of wrinkles when the critical
fracture strength of the coating is exceeded. For the UV treated samples, through
thickness cracks are possibly impacted by the formation of an embrittled near
surface PDMS layer.
PMID- 28517010
TI - Suppression of near band edge emission in specially engineered ZnO twin nanorods.
AB - We report the synthesis of a unique zinc oxide nanorod structure in which an
amorphous ZnO layer is sandwiched between two identical crystalline segments of
ZnO. A simple hydrothermal reaction method was used for this purpose, which
allowed us to tune the amorphous and crystalline sections of the nanorods via
reaction temperature. A systematic study of the morphology and dimensions of the
nanorods grown under various conditions was performed using a combination of
scanning and transmission electron microscopy. Transmission electron microscopy
(TEM) clearly showed an amorphous separation between the two crystalline
segments. UV-vis absorption spectroscopy of the twin nanorods (TNRs) showed a
redshift in the optical band gap as a function of the growth duration, indicating
slightly stressed growth of the crystalline segments. For a longer growth
duration, as the amorphous gap starts to get bridged by crystalline growth,
redshift in optical band gap becomes constant. This confirms a true mechanical
gap between the two crystalline segments of the nanorods. Temperature dependent
photoluminescence (PL) spectra of the TNRs showed a variation in free exciton
(FX) emission energy, which fitted very well to a model incorporating lattice
dilation in addition to the standard electron-phonon interactions. At low
temperatures (below ~180 K) we observed the appearance of visible emission peaks
due to localization of defect levels. A loss in the near band edge emission
intensity was observed at low temperatures, commensurate with the appearance of
defect emission in the visible range.
PMID- 28517011
TI - Dissection of H-bonding interactions in a glycolic acid-water dimer.
AB - The binding strength and collective effects of multiple H-bonds in the glycolic
acid-water dimer were studied in comparison to the aromatic analog, 9-hydroxy-9
fluorene carboxylic acid (9HFCA). Quantitative analysis by the generalized Kohn
Sham energy decomposition analysis shows that the energy difference in each
specific physical interaction, from a glycolic acid-water dimer to a 9HFCA-water
dimer, is small and amounts to less than 5% of the binding energy of the 9HFCA
water dimer. Extensive comparison of further, similar H-bonded complexes with
widely varying binding strengths reinforces their excellent analogy in that the
fluorene group acts as a non-interfering spectator for intermolecular H-bonding
interactions. With reference to the spectroscopic measurement on the 9HFCA-water
dimer (8.51 +/- 0.09 kcal mol-1), the binding energy of the glycolic acid-water
dimer is estimated to be 8.51 +/- 0.31 kcal mol-1, a much better accuracy than
previous reports. Furthermore, correlating the infrared spectra of 9HFCA H-bonded
complexes provides a circumstantial probing of the existence and consequences of
cooperative and anti-cooperative behaviors in the glycolic acid-water dimer. Our
studies point to the interesting H-bonding phenomena in the glycolic acid-water
dimer, which may inspire challenging experiments in future.
PMID- 28517012
TI - Re-characterization of hammerhead ribozymes as molecular tools for intermolecular
RNA cleavage.
AB - A new guideline for the construction of hammerhead ribozymes to achieve trans
cleavage of a single-stranded RNA molecule was developed. The sequence rule of
the HHRz cleavage site was highly recommended to be "DWH" with an optimal binding
arm length of 8-9nt, which diverged from the former rule of "NUX".
PMID- 28517013
TI - Incipient microphase separation in short chain perfluoropolyether-block
poly(ethylene oxide) copolymers.
AB - Incipient microphase separation is observed by wide angle X-ray scattering (WAXS)
in short chain multiblock copolymers consisting of perfluoropolyether (PFPE) and
poly(ethylene oxide) (PEO) segments. Two PFPE-PEO block copolymers were studied;
one with dihydroxyl end groups and one with dimethyl carbonate end groups.
Despite having a low degree of polymerization (N ~ 10), these materials exhibited
significant scattering intensity, due to disordered concentration fluctuations
between their PFPE-rich and PEO-rich domains. The disordered scattering intensity
was fit to a model based on a multicomponent random phase approximation to
determine the value of the interaction parameter, chi, and the radius of
gyration, Rg. Over the temperature range 30-90 degrees C, the values of chi were
determined to be very large (~2-2.5), indicating a high degree of immiscibility
between the PFPE and PEO blocks. In PFPE-PEO, due to the large electron density
contrast between the fluorinated and non-fluorinated block and the high value of
chi, disordered scattering was detected at intermediate scattering angles, (q ~ 2
nm-1) for relatively small polymer chains. Our ability to detect concentration
fluctuations was enabled by both a relatively large value of chi and significant
scattering contrast.
PMID- 28517014
TI - N-Atom transfer via thermal or photolytic activation of a Co-azido complex with a
PNP pincer ligand.
AB - Thermal or photolytic activation of well-defined mononuclear [Co(N3)(PNP)] (PNP =
2,2'-bis(diisopropylphosphino)-4,4'-ditolylamido) results in the structurally
characterized dinuclear species [Co(MU-N;kappa3-P,N,N-PNPN)]2 (3), with two N
bridging phosphiniminato bridgeheads. Density Functional Theory (DFT)
calculations indicate the intermediacy of a mononuclear cobalt-nitrido complex,
followed by N-migratory insertion into a Co-P bond. Reaction of 3 with two equiv.
HCl leads to rupture of the dimer with formation of mononuclear [CoCl(PNPNH)] (4)
by protonation of the N-bridges.
PMID- 28517016
TI - Graphene as an electrode for solution-processed electron-transporting organic
transistors.
AB - Organic field-effect transistors (OFETs) are fundamental building blocks for
plastic electronics such as organic photovoltaics or bendable displays with
organic light emitting diodes, and radio-frequency identification (RFID) tags. A
key part in the performance of OFET is the organic material constituting the
channel. OFETs based on solution-processed polymers represent a new class of
organic electronic devices. Recent developments in upscale solution-processed
polymers have advanced towards high throughput, low-cost, and environmentally
friendly materials for high-performance applications. Together with the
integration of high performance materials, another enduring challenge in OFET
development is the improvement and control of the injection of charge carriers.
Graphene, a two-dimensional layer of covalently bonded carbon atoms, is steadily
making progress into applications relying on van der Waals heterointerfaces with
organic semiconductors. Here, we demonstrate the versatile operation of solution
processed organic transistors both in lateral and vertical geometries by
exploiting the weak-screening effect and work function modulation properties of
graphene electrodes. Our results demonstrate a general strategy for overcoming
traditional noble metal electrodes and to integrate graphene with solution
processed Polyera ActiveInkTM N2200 polymer transistors for high-performance
devices suitable for future plastic electronics.
PMID- 28517015
TI - Genetic incorporation of 4-fluorohistidine into peptides enables selective
affinity purification.
AB - Due to the lowered pKa of 4-fluorohistidine relative to histidine, peptides and
proteins containing this amino acid are potentially endowed with novel
properties. We report here the optimized synthesis of 4-fluorohistidine and show
that it can efficiently replace histidine in in vitro translation reactions.
Moreover, peptides containing 6*-fluorohistidine tags are able to be selectively
captured and eluted from nickel resin in the presence of his-tagged protein
mixtures.
PMID- 28517020
TI - Au-Cu core-shell nanocube-catalyzed click reactions for efficient synthesis of
diverse triazoles.
AB - Au-Cu core-shell nanocubes and octahedra synthesized in aqueous solution were
employed to catalyze a 1,3-dipolar cycloaddition reaction between phenylacetylene
and benzyl azide in water at 50 degrees C for 3 h. Interestingly, the nanocubes
were far more efficient in catalyzing this reaction, giving 91% yield of a
regioselective 1,4-triazole product, while octahedra only recorded 46% yield. The
Au-Cu nanocubes were subsequently employed to catalyze the click reaction between
benzyl azide and a broad range of aromatic and aliphatic alkynes. The product
yields ranged from 78 to 99%. Clearly the Au-Cu cubes exposing {100} surfaces are
an excellent and green catalyst for click reactions.
PMID- 28517021
TI - Low discriminating power of the modified Ottawa VTE risk score in a cohort of
patients with cancer from the RIETE registry.
AB - Treatment of patients with cancer-associated venous thromboembolism (VTE) remains
a major challenge. The modified Ottawa score is a clinical prediction rule
evaluating the risk of VTE recurrences during the first six months of
anticoagulant treatment in patients with cancer-related VTE. We aimed to validate
the Ottawa score using data from the RIETE registry. A total of 11,123 cancer
patients with VTE were included in the analysis. According to modified Ottawa
score, 2,343 (21 %) were categorised at low risk for VTE recurrences, 4,525 (41
%) at intermediate risk, and 4,255 (38 %) at high risk. Overall, 477 episodes of
VTE recurrences were recorded during the course of anticoagulant therapy, with an
incidence rate for low, intermediate, and high risk groups of 6.88 % (95 % CI
5.31-8.77), 11.8 % (95 % CI 10.1-13.6), and 21.3 % (95 % CI 18.8-24.1) patient
years, respectively. Overall mortality had an incidence rate of 21.1 % (95 % CI
18.2-24.3), 79.4 % (95 % CI: 74.9-84.1), and 134.7 % (95 % CI: 128.3-141.4)
patient-years, respectively. The accuracy and discriminating power of the
modified Ottawa score for VTE recurrence was modest, with low sensitivity,
specificity and positive predictive value, and a C-statistics of 0.58 (95 % CI:
0.56-0.61). In our analysis, the modified Ottawa score did not accurately predict
VTE recurrence among patients with cancer-associated thrombosis, thus hindering
its use in clinical practice. It is time to define a new score including other
clinical predictors.
PMID- 28517022
TI - Impact and management of left ventricular function on the prognosis of Takotsubo
syndrome.
AB - BACKGROUND: Early research has proposed that patients with Takotsubo syndrome
(TTS) could have a higher mortality rate than the general population. Our study
was conducted to determine the short- and long-term outcome of TTS patients
associated with a significantly compromised left ventricular function on hospital
admission. MATERIALS AND METHODS: Our institutional database constituted a
collective of 112 patients diagnosed with TTS between 2003 and 2015. The patients
were classified into two groups based on the left ventricular ejection fraction
(LVEF), with those presenting with a LVEF > 35% on admission categorized into one
group (n = 65, 58%) and those presenting with LVEF <= 35% (n=47, 42%) categorized
into another group. The endpoint was the all-cause of mortality over a mean
follow-up of 1529 +/- 1121 days. RESULTS: Preliminary results indicated that
patients with an EF <= 35% had a significantly greater risk of developing life
threatening arrhythmias, and were much more likely to suffer from cardiogenic
shock. Patients often required varying forms of mechanical respiratory support.
The in-hospital mortality, 30-day mortality, 1-year mortality and ongoing long
term mortality was significantly higher in TTS patients with an EF <= 35%. In a
multivariate Cox regression analysis, an EF <= 35% (HR 3.3, 95% CI: 1.2-9.2, P <
0.05) was identified as a strong independent predictor of the primary endpoint.
CONCLUSIONS: In-hospital events as well as short- and long-term mortality rates
among TTS patients diagnosed with a significantly reduced LVEF on admission were
significantly higher. There is an urgent need for randomized trials, which could
help define uniform clinical management strategies for high risk TTS patients.
PMID- 28517023
TI - Shifts in water availability mediate plant-pollinator interactions.
AB - Altered precipitation patterns associated with anthropogenic climate change are
expected to have many effects on plants and insect pollinators, but it is unknown
if effects on pollination are mediated by changes in water availability. We
tested the hypothesis that impacts of climate on plant-pollinator interactions
operate through changes in water availability, and specifically that such effects
occur through alteration of floral attractants. We manipulated water availability
in two naturally occurring Mertensia ciliata (Boraginaceae) populations using
water addition, water reduction and control plots and measured effects on
vegetative and floral traits, pollinator visitation and seed set. While most
floral trait values, including corolla size and nectar, increased linearly with
increasing water availability, in this bumblebee-pollinated species, pollinator
visitation peaked at intermediate water levels. Visitation also peaked at an
intermediate corolla length, while its relationship to corolla width varied
across sites. Seed set, however, increased linearly with water. These results
demonstrate the potential for changes in water availability to impact plant
pollinator interactions through pollinator responses to differences in floral
attractants, and that the effects of water on pollinator visitation can be
nonlinear. Plant responses to changes in resource availability may be an
important mechanism by which climate change will affect species interactions.
PMID- 28517024
TI - Treatment of severe alcoholic hepatitis: past, present and future.
AB - Alcoholic hepatitis (AH) manifests as a clinical syndrome characterized by recent
jaundice and liver function deterioration in an actively drinking patient. The
principal cause of AH is alcoholic steatohepatitis (ASH) defined histologically
by the coexistence of steatosis, hepatocyte ballooning and satellitosis. While
nonsevere AH usually responds to alcohol abstinence, severe AH, identified by
Maddrey scoring >= 32, has a bad prognosis and is traditionally treated by a 28
day course of prednisone therapy. A recent trial, which showed no improvement of
long-term survival but significant reduced mortality after 28 days of corticoid
therapy compared to placebo, opens a debate on its efficacy. N-acetyl-cysteine
supplementation combined with steroid therapy is also able to reduce the 28-day
mortality compared to steroid alone. While guidelines recommend high-calorie
intake and protein supplementation in decompensated liver diseases, intensive
enteral nutrition together with corticoid treatment does not reduce mortality
compared to corticoid alone in a recent study with ASH patients. Stimulation of
liver regeneration through interleukin-22, granulocyte colony-stimulating factor
or farnesoid X receptor agonists, inhibition of apoptosis, early liver
transplantation and modulation of gut microbiota through antibiotic or faecal
transplantation approaches constitute new therapeutic perspectives that are
investigated in current clinical trials. Inhibition of oxidative stress,
modulation of gut fungal populations and stimulation of progenitor cell
proliferation and pro-regenerative inflammatory pathways constitute prospects for
future human trials. For long-term survival, strategies for persistent alcohol
abstinence remain the key of success, opening another large research field.
PMID- 28517026
TI - Impact of severe tricuspid regurgitation on accuracy of systolic pulmonary
arterial pressure measured by Doppler echocardiography: Analysis in an unselected
patient population.
AB - Pulmonary arterial pressure is an important index in cardiovascular disorders,
especially for pulmonary hypertension (PH). Doppler echocardiography (DE) is
widely used as a noninvasive method to assess pulmonary arterial pressure.
However, recent studies have found several hemodynamic factors that affect its
accuracy in estimating systolic pulmonary arterial pressure (sPAP). But the
effect of tricuspid regurgitation (TR) has not been investigated. Therefore, our
study is aimed to determine whether the severity of TR will affect the accuracy
of sPAP measured by DE in an unselected patient population. We retrospectively
studied 177 patients who underwent DE and right heart catheterization (RHC)
examinations. Patients were categorized into 3 groups according to the severity
of TR (mild, moderate, and severe). The discrepancy in sPAP measured by DE and
RHC was calculated and compared in each group. Determinants of discordant results
between two methods were also evaluated. Age, gender, interval between DE and
RHC, sequence of DE and RHC were similar among groups (all P>.05). Differences in
sPAP, RAP, and tricuspid regurgitation pressure gradient (TR-PG) were similar in
group 1 and 2 (all P>.05), while all significantly higher in group 3 (all P<.05).
The difference in sPAP between DE and RHC was affected independently by severe TR
and severe PH (both P<.05). Severe TR and severe PH affect the accuracy of sPAP
measured by DE. Modification of echocardiographic sPAP measurements by taking
into consideration of these factors may lead to reduced systemic errors.
PMID- 28517027
TI - Lung function parameters in omalizumab responder patients: An interesting tool?
AB - BACKGROUND: Omalizumab, an anti-IgE antibody, is used to treat patients with
severe allergic asthma. The evolution of lung function parameters over time and
the difference between omalizumab responder and nonresponder patients remain
inconclusive. The objective of this real-life study was to compare the changes in
forced expiratory volume in 1 second (FEV1) of omalizumab responders and
nonresponders at 6 months. METHODS: A multicenter analysis was performed in 10
secondary and tertiary institutions. Lung function parameters (forced vital
capacity (FVC), pre- and postbronchodilator FEV1, residual volume (RV), and total
lung capacity (TLC) were determined at baseline and at 6 months. Omalizumab
response was assessed at the 6-month visit. In the omalizumab responder patients,
lung function parameters were also obtained at 12, 18, and 24 months. RESULTS:
Mean prebronchodilator FEV1 showed improvement in responders at 6 months, while a
decrease was observed in nonresponders (+0.2+/-0.4 L and -0.1+/-0.4 L,
respectively, P<.01). After an improvement at 6 months, pre- and
postbronchodilator FEV1 remained stable at 12, 18, and 24 months. The FEV1/FVC
remained unchanged over time, but the proportion of patients with an FEV1/FVC
ratio <0.7 decreased at 6, 12, 18, and 24 months (55.2%, 54.0%, 54.0%, and 44.8%,
respectively, P<.05). Mean RV values decreased at 6 months but increased at 12
months and 24 months (P<.05). Residual volume/total lung capacity (RV/TLC) ratio
decreased at 6 months and remained unchanged at 24 months. CONCLUSION: After
omalizumab initiation, FEV1 improved at 6 months in responder patients and then
remained stable for 2 years. RV and RV/TLC improved at 6 months.
PMID- 28517028
TI - AIC identifies optimal representation of longitudinal dietary variables.
AB - OBJECTIVES: The Akaike Information Criterion (AIC) is a well-known tool for
variable selection in multivariable modeling as well as a tool to help identify
the optimal representation of explanatory variables. However, it has been
discussed infrequently in the dental literature. The purpose of this paper is to
demonstrate the use of AIC in determining the optimal representation of dietary
variables in a longitudinal dental study. METHODS: The Iowa Fluoride Study
enrolled children at birth and dental examinations were conducted at ages 5, 9,
13, and 17. Decayed or filled surfaces (DFS) trend clusters were created based on
age 13 DFS counts and age 13-17 DFS increments. Dietary intake data (water, milk,
100 percent-juice, and sugar sweetened beverages) were collected semiannually
using a food frequency questionnaire. Multinomial logistic regression models were
fit to predict DFS cluster membership (n=344). Multiple approaches could be used
to represent the dietary data including averaging across all collected surveys or
over different shorter time periods to capture age-specific trends or using the
individual time points of dietary data. RESULTS: AIC helped identify the optimal
representation. Averaging data for all four dietary variables for the whole
period from age 9.0 to 17.0 provided a better representation in the multivariable
full model (AIC=745.0) compared to other methods assessed in full models
(AICs=750.6 for age 9 and 9-13 increment dietary measurements and AIC=762.3 for
age 9, 13, and 17 individual measurements). The results illustrate that AIC can
help researchers identify the optimal way to summarize information for inclusion
in a statistical model. CONCLUSIONS: The method presented here can be used by
researchers performing statistical modeling in dental research. This method
provides an alternative approach for assessing the propriety of variable
representation to significance-based procedures, which could potentially lead to
improved research in the dental community.
PMID- 28517030
TI - Gerbode defect and multivalvular dysfunction: Complex complications in adult
congenital heart disease.
AB - We report a clinical case of a 40-year-old male with surgically corrected
congenital heart disease (CHD) 10 years earlier: closure of ostium primum, mitral
annuloplasty, and aortic valve and root surgery. The patient was admitted with
acute heart failure. Transesophageal echocardiography (TEE) revealed a dysmorphic
and severely incompetent aortic valve, a partial tear of the mitral valve cleft
repair and annuloplasty ring dehiscence. A true left ventricular-to-right atrial
shunt confirmed a direct Gerbode defect. The authors aim to discuss the
diagnostic challenge of adult CHD, namely the key role of TEE on septal defects
and valve regurgitations description.
PMID- 28517029
TI - Carbon-driven enrichment of the crucial nitrate-reducing bacteria in limed peat
soil microcosms.
AB - : Bacteria of Dechloromonas were recognized as potential functional important
denitrifiers in a long-term shell sand-amended peat soil. Different microcosms in
a solid matrix and slurry systems with the addition of carbon and nitrogen
sources, for example, clover leaves, glutamate and nitrate, were established. The
bacterial community structures were analysed by pyrosequencing of the 16S rRNA
gene to select the conditions for enriching bacteria of Dechloromonas. The
results showed that a relatively even bacterial community in the initial soil
shifted to communities dominated by a few types of nitrate-reducing bacteria
after the incubation, which strongly responded to the carbon substrates addition
and consumption. The bacteria of several genera including Dechloromonas,
Pseudomonas, Clostridium, Aeromonas and Ferribacterium were significantly
enriched after a certain period of time. The bacteria of Dechloromonas became one
of the most predominant bacteria in the incubated community. Especially when
added the mixed carbon substrates into the solid soil matrix, as high as 34% of
abundance was detected. This study proved that the functional important bacteria
from the genus of Dechloromonas could be enriched to an extremely high abundance
by using proper culture condition which will benefit to the isolation or direct
metagenomics study for Dechloromonas. SIGNIFICANCE AND IMPACT OF THE STUDY: The
study of key players in a microbial community is always of important. In this
study, the functional important denitrifiers in a shell sand-amended peat soil
were investigated. Using different carbon sources in the incubation, we found the
bacteria from the genus of Dechloromonas were enriched to an abundance of higher
than 34% with several other denitrifiers together. This work provides us helpful
insights not only for knowing the diversity of denitrifiers in the studied peat
soil, but also for understanding their response to the carbon sources and the
culture conditions.
PMID- 28517031
TI - An isolated ulcerated forehead lesion in a 70-year-old man.
PMID- 28517032
TI - Novel psychoactive substance consumption is more represented in bipolar disorder
than in psychotic disorders: A multicenter-observational study.
AB - OBJECTIVE: Comorbidities between psychiatric diseases and use of traditional
substances of abuse are common. Nevertheless, there are few data regarding the
use of novel psychoactive substances (NPS) among psychiatric patients. Aim of
this multicentre survey is to investigate the consumption of a number of
psychoactive substances in a young psychiatric sample. METHODS: Between December
2013 and September 2015, a questionnaire was administered in 10 Italian
psychiatric care facilities to a sample of 671 patients, aged 18-26 (mean age
22.24; SD 2.87). RESULTS: About 8.2% of the sample declared to have used NPS at
least once, and 2.2% had consumed NPS in the previous 3 months. The three
psychiatric diagnoses most frequently associated with NPS use were bipolar
disorder (23.1%), personality disorders (11.8%), and schizophrenia and related
disorders (11.6%). In univariate regression analysis, bipolar disorder was
positively associated with NPS consumption, an association that did not reach
statistical significance in the multivariate analysis. CONCLUSIONS: The use of
NPS in a young psychiatric population appears to be frequent, and probably still
underestimated. Bipolar disorder shows an association with NPS use. Careful and
constant monitoring and an accurate evaluation of possible clinical effects
related to NPS use are necessary.
PMID- 28517033
TI - High-throughput sequencing of transposable element insertions suggests adaptive
evolution of the invasive Asian tiger mosquito towards temperate environments.
AB - Invasive species represent unique opportunities to evaluate the role of local
adaptation during colonization of new environments. Among these species, the
Asian tiger mosquito, Aedes albopictus, is a threatening vector of several human
viral diseases, including dengue and chikungunya, and raises concerns about the
Zika fever. Its broad presence in both temperate and tropical environments has
been considered the reflection of great "ecological plasticity." However, no
study has been conducted to assess the role of adaptive evolution in the
ecological success of Ae. albopictus at the molecular level. In the present
study, we performed a genomic scan to search for potential signatures of
selection leading to local adaptation in one-hundred-forty field-collected
mosquitoes from native populations of Vietnam and temperate invasive populations
of Europe. High-throughput genotyping of transposable element insertions led to
the discovery of more than 120,000 polymorphic loci, which, in their great
majority, revealed a virtual absence of structure between the biogeographic
areas. Nevertheless, 92 outlier loci showed a high level of differentiation
between temperate and tropical populations. The majority of these loci segregate
at high insertion frequencies among European populations, indicating that this
pattern could have been caused by recent adaptive evolution events in temperate
areas. An analysis of the overlapping and neighbouring genes highlighted several
candidates, including diapause, lipid and juvenile hormone pathways.
PMID- 28517035
TI - A Biomass-Derived Non-Noble Cobalt Catalyst for Selective Hydrodehalogenation of
Alkyl and (Hetero)Aryl Halides.
AB - Hydrodehalogenation is a straightforward approach for detoxifications of harmful
anthropogenic organohalide-based pollutants, as well as removal of halide
protecting groups used in multistep syntheses. A novel sustainable catalytic
material was prepared from biowaste (chitosan) in combination with an earth
abundant cobalt salt. The heterogeneous catalyst was fully characterized by
transmission electron microscope, X-ray diffraction, and X-ray photoelectron
spectroscopy measurements, and successfully applied to hydrodehalogenation of
alkyl and (hetero)aryl halides with broad scope (>40 examples) and excellent
chemoselectivity using molecular hydrogen as a reductant. The general usefulness
of this method is demonstrated by successful detoxification of non-degradable
pesticides and fire retardants. Moreover, the potential of the catalyst as a
deprotection tool is demonstrated in a multistep synthesis of (+/-)-peronatin B
(alkaloid).
PMID- 28517036
TI - Prevalence of muscle weakness based on different diagnostic criteria in community
dwelling older adults: A comparison of grip strength dynamometers.
AB - AIM: The present study compared the performance of the Jamar and Smedley
dynamometers for the measurement of grip strength, and the two dynamometers were
used to determine the prevalence rate of weakness in a large, community-dwelling,
older adult population, based on different diagnostic criteria. METHODS: A total
of 467 community-dwelling older adults aged 69-89 years were recruited into the
study. Grip strength was measured with two dynamometers; the Jamar hydraulic hand
dynamometer was used as the reference device. To assess agreement between grip
strength measurements by the two dynamometers, linear regression and Bland-Altman
analyses were carried out. RESULTS: In a comparison of the dynamometers, high
coefficients of determination (R2 ) were obtained for grip strength (R2 = 0.80,
standard error of the estimate 2.68 kg in male participants, and R2 = 0.75,
standard error of the estimate = 1.95 kg in female participants). There was
systematic bias with underestimation of grip strength (bias 3.09 kg, 95%
confidence interval 2.77 to 3.41 for men; bias 2.60 kg, 95% confidence interval
2.31 to 2.89 for women) by the Smedley dynamometer. In both sexes, no
proportional bias was noted between the two dynamometers for measurement of grip
strength (r = 0.030, P = 0.611 for male participants; r = -0.033, P = 0.653 for
female participants). The prevalence of weakness ranged from 1.8 to 19.9% in male
participants, and 0.5 to 27.4% in female participants. CONCLUSIONS: The present
study shows that despite the excellent correlation between the two dynamometers,
there is a statistically significant difference in grip strength measurements.
The Smedley dynamometer showed a higher prevalence of weakness than did the Jamar
dynamometer. Geriatr Gerontol Int 2017; 17: 2089-2095.
PMID- 28517034
TI - Comparative musculoskeletal anatomy of chameleon limbs, with implications for the
evolution of arboreal locomotion in lizards and for teratology.
AB - Chameleon species have recently been adopted as models for evo-devo and
macroevolutionary processes. However, most anatomical and developmental studies
of chameleons focus on the skeleton, and information about their soft tissues is
scarce. Here, we provide a detailed morphological description based on contrast
enhanced micro-CT scans and dissections of the adult phenotype of all the
forelimb and hindlimb muscles of the Veiled Chameleon (Chamaeleo calyptratus) and
compare these muscles with those of other chameleons and lizards. We found the
appendicular muscle anatomy of chameleons to be surprisingly conservative
considering the remarkable structural and functional modifications of the limb
skeleton, particularly the distal limb regions. For instance, the zygodactyl
autopodia of chameleons are unique among tetrapods, and the carpals and tarsals
are highly modified in shape and number. However, most of the muscles usually
present in the manus and pes of other lizards are present in the same
configuration in chameleons. The most obvious muscular features related to the
peculiar opposable autopodia of chameleons are: (1) presence of broad, V-shaped
plantar and palmar aponeuroses, and absence of intermetacarpales and
intermetatarsales, between the digits separated by the cleft in each autopod; (2)
oblique orientation of the superficial short flexors originating from these
aponeuroses, which may allow these muscles to act as powerful adductors of the
"super-digits"; and (3) well-developed abductor digiti minimi muscles and
abductor pollicis/hallucis brevis muscles, which may act as powerful abductors of
the "super-digits."
PMID- 28517038
TI - Do trainees feel that they belong to a team?
AB - BACKGROUND: Postgraduate medical education has undergone significant
reorganisation in recent years, with changes to the traditional apprenticeship
model and an increasing reliance on shift working. The importance of teamwork in
clinical care is well established; however, there is little literature on the
extent to which trainees actually feel part of a team in the context of current
working patterns. METHOD: This is a qualitative study using semi-structured
interviews of medical and surgical trainees. Data were analysed thematically
using an inductive qualitative approach. RESULTS: Fifteen trainees who had worked
in a range of hospitals across the UK participated. Emerging themes fell into
several categories: what constitutes the team; the effect of shift patterns on
the team; the role of the team in education, support and well-being; and
influences on team rapport. Whilst in general interviewees felt part of a team,
this was not true for all posts. The nature of the team was also highly variable,
and had evolved from the traditional 'Firm' structure to a more nebulous concept.
Shift-working patterns could result in the fragmentation of the team, which had
implications for patient care as well as for training. DISCUSSION: The team
played an important role in both education and well-being for trainees, and
several factors were identified that could engender a more supportive team. With
an ageing population and with increasing demands on limited resources, the
requirement for shift work is likely to increase, and there is a fundamental need
to maintain support for the next generation of doctors. There is little
literature on the extent to which trainees actually feel part of a team.
PMID- 28517037
TI - Serum phosphate is related to adiposity in healthy adults.
AB - BACKGROUND: Inorganic phosphate is a crucial component of cellular energy
metabolism. We have identified an inverse relationship between serum phosphate
concentration and fat mass in a cohort of healthy men. This study reports those
data and determines whether this association is present in two female
populations. METHODS: Cross-sectional data from three independent cohorts,
consisting of healthy adult males (Male Cohort, n = 323) and healthy
postmenopausal women (Female Cohort 1, n = 185; and Female Cohort 2, n = 1471),
are reported. Associations between serum phosphate and weight, body mass index
(BMI), fat mass and bone mineral density (BMD) were assessed. In a fourth cohort
of postmenopausal women (FGF23 Cohort, n = 20), associations between fibroblast
growth factor 23 (FGF23), weight and BMI were assessed. RESULTS: Serum phosphate
correlated inversely with weight, BMI and fat mass across all three cohorts (r =
0.13 to -0.31, P < 0.0001-0.02). Associations were diminished after adjustment
for PTH, but remained significant. In the FGF23 Cohort, FGF23 was positively
correlated with weight (r = 0.60, P = 0.007) and BMI (r = 0.49, P = 0.03).
Phosphate was inversely associated with BMD in Female Cohorts 1 and 2 (r = -0.08
to -0.29, P < 0.0001-0.02). This relationship was attenuated, but remained
significant at most sites, following adjustment for age, fat mass, renal function
and 25-hydroxyvitamin D. CONCLUSIONS: Serum phosphate is inversely associated
with measures of adiposity in both women and men, largely independently of PTH.
FGF23 might mediate these associations. This relationship may be an unrecognized
confounder in some of the correlates of serum phosphate already described.
PMID- 28517039
TI - Genetics of mycorrhizal symbiosis in winter wheat (Triticum aestivum).
AB - Bread wheat (Triticum aestivum) is a major staple food and therefore of prime
importance for feeding the Earth's growing population. Mycorrhiza is known to
improve plant growth, but although extensive knowledge concerning the interaction
between mycorrhizal fungi and plants is available, genotypic differences
concerning the ability of wheat to form mycorrhizal symbiosis and quantitative
trait loci (QTLs) involved in mycorrhization are largely unknown. Therefore, a
diverse set of 94 bread wheat genotypes was evaluated with regard to root
colonization by arbuscular mycorrhizal fungi. In order to identify genomic
regions involved in mycorrhization, these genotypes were analyzed using the wheat
90k iSelect chip, resulting in 17 823 polymorphic mapped markers, which were used
in a genome-wide association study. Significant genotypic differences (P <
0.0001) were detected in the ability to form symbiosis and 30 significant markers
associated with root colonization, representing six QTL regions, were detected on
chromosomes 3A, 4A and 7A, and candidate genes located in these QTL regions were
proposed. The results reported here provide key insights into the genetics of
root colonization by mycorrhizal fungi in wheat.
PMID- 28517040
TI - Thoughts of being an imposter, in medical students.
PMID- 28517041
TI - Modifying illness beliefs in recent onset psychosis carers: Evaluating the impact
of a cognitively focused brief group intervention in a routine service.
AB - AIMS: At first-episode psychosis (FEP), many patients will be routed within
familial networks and supported by informal carers who are predominately close
family members such as parents. Carer burden, distress and poorer coping styles
are associated with different illness beliefs. The current study sought to
examine the impact and acceptability of a 3 session, cognitively informed, group
intervention targeting illness beliefs previously linked to distress and poorer
caregiving experiences in FEP carers. METHODS: Carers attending a routine FEP
service were invited to attend the group intervention and completed a measure of
illness beliefs at baseline and post intervention. RESULTS: Data on 68 carers
with complete datasets are presented. Carers were predominately females (64.2%).
Group attendance was linked to positive improvements in carer baseline beliefs
about the negative consequences of the illness for the patient and themselves,
attributions of blame about the illness to the patient and themselves and their
overall understanding about the illness. Significant improvements in their
understanding of the illness timeline and course, and confidence in dealing with
difficulties were also identified. CONCLUSIONS: A cognitively informed group
approach to targeting the less adaptive illness beliefs reported by FEP carers
may offer an effective and acceptable pathway to facilitate their understanding
of the illness and adjustment. Further studies using controlled designs are
required.
PMID- 28517042
TI - The Impact of the ACA Medicaid Expansions on Health Insurance Coverage through
2015 and Coverage Disparities by Age, Race/Ethnicity, and Gender.
AB - OBJECTIVE: Examine the ACA Medicaid expansion effects on Medicaid take-up and
private coverage through 2015 and coverage disparities by age, race/ethnicity,
and gender. DATA SOURCES: 2011-2015 American Community Survey for 3,137,989 low
educated adults aged 19-64 years. STUDY DESIGN: Difference-in-differences
regressions accounting for national coverage trends and state fixed effects.
PRINCIPAL FINDINGS: Expansion effects doubled in 2015 among low-educated adults,
with a nearly 8 percentage-point increase in Medicaid take-up and 6 percentage
point decline in uninsured rate. Significant coverage gains were observed across
virtually all examined groups by age, gender, and race/ethnicity. Take-up and
insurance declines were strongest among younger adults and were generally close
by gender and race/ethnicity. Despite the increased take-up however, coverage
disparities remained sizeable, especially for young adults and Hispanics who had
declining but still high uninsured rates in 2015. There was some evidence of
private coverage crowd-out in certain subgroups, particularly among young adults
aged 19-26 years and women, including in both individually purchased and employer
sponsored coverage. CONCLUSIONS: The ACA Medicaid expansions have continued to
increase coverage in 2015 across the entire population of low-educated adults and
have reduced age disparities in coverage. However, there is still a need for
interventions that target eligible young and Hispanic adults.
PMID- 28517044
TI - Intercentrum versus pleurocentrum growth in early tetrapods: A paleohistological
approach.
AB - A variety of vertebral centrum morphologies have evolved within early tetrapods
which range from multipartite centra consisting of intercentra and pleurocentra
in stem-tetrapods, temnospondyls, seymouriamorphs, and anthracosaurs up to
monospondylous centra in lepospondyls. With the present study, we aim to
determine the formation of both intercentrum and pleurocentrum and asked whether
these can be homologized based on their bone histology. Both intercentra and
pleurocentra ossified endochondrally and periosteal bone was subsequently
deposited on the outer surface of the centra. Our observations indicate low
histological variation between intercentrum and pleurocentrum in microstructural
organization and growth which inhibits the determination of homologies. However,
intercentrum and pleurocentrum development differs during ontogeny. As previously
assumed, the intercentrum arises from ventrally located and initially paired
ossification centers that fuse ventromedially to form the typical, crescentic,
rhachitomous intercentrum. In contrast, presacral pleurocentra may be ancestrally
represented by four ossification centers: a ventral and a dorsal pair.
Subsequently, two divergent developmental patterns are observed: In stem
tetrapods and temnospondyls, the pleurocentrum evolves from the two dorsally
located ossification centers which may occasionally fuse to form a dorsal
crescent. In some dvinosaurian temnospondyls, the pleurocentrum may even ossify
to full rings. In comparison, the pleurocentrum of stem-amniotes (anthracosaurs,
chroniosuchids, seymouriamorphs, and lepospondyls) arises from the two ventrally
located ossification centers whereby the ossification pattern is almost identical
to that of temnospondyls but mirror-inverted. Thus, the ring-shaped pleurocentrum
of Discosauriscus ossifies from ventral to dorsal. We also propose that the
ossified portions of the intercentrum and pleurocentrum continued as
cartilaginous rings or discs that surrounded the notochord in the living animals.
PMID- 28517043
TI - Sperm chromatin quality and DNA integrity in partial versus total
globozoospermia.
AB - Globozoospermia is a severe form of teratozoospermia with low incidence in
infertile patients, considered as one of the important causes of male
infertility. The objective was to investigate the chromatin/DNA integrity as well
as apoptosis in ejaculated spermatozoa of cases with partial or total
globozoospermia. Fifty-seven semen samples were divided into three groups of
partial globozoospermia (n = 17), total globozoospermia (n = 10) and
normozoospermia (control; n = 30). Sperm chromatin condensation, DNA integrity
and apoptosis were assessed using cytochemical assays. The results showed
significant differences in sperm parameters of count and motility between two
case groups versus controls. The percentages of spermatozoa with abnormal
chromatin packaging and protamine deficiency were significantly higher in total
and partial globozoospermic men compared to normozoospermic samples. Also, the
rates of TUNEL-positive spermatozoa were significantly increased in both
globozoospermic cases with respect to the control (18.3 +/- 10.1 and 12.3 +/- 9.2
versus 5.9 +/- 3 respectively). However, no significant differences were noticed
between two subgroups of patients with regard to sperm DNA denaturation, DNA
fragmentation and apoptosis. Abnormal chromatin packaging, DNA damage and
apoptosis were significantly higher in cases than controls. The sperm
chromatin/DNA anomalies may be considered as one of the main aetiology of ART
failure in globozoospermic patients.
PMID- 28517046
TI - Three-dimensional proximal flow convergence automatic calculation for determining
mitral valve area in rheumatic mitral stenosis.
AB - PURPOSE: Management of patients with mitral stenosis (MS) depends heavily on the
accurate quantification of mitral valve area (MVA) using echocardiography. All
currently used two-dimensional (2D) methods have limitations. Estimation of MVA
using the proximal isovelocity surface area (PISA) method with real time three
dimensional (3D) echocardiography may circumvent those limitations. We aimed to
evaluate the accuracy of 3D direct measurement of PISA in the estimation of MVA.
METHODS: Twenty-seven consecutive patients (median age of 63 years; 77.8%
females) with rheumatic MS were prospectively studied. Transthoracic and
transesophageal echocardiography with 2D and 3D acquisitions were performed on
the same day. The reference method for MVA quantification was valve planimetry
after 3D-volume multiplanar reconstruction. A semi-automated software was used to
calculate the 3D flow convergence volume. RESULTS: Compared to MVA estimation
using 3D planimetry, 3D PISA showed the best correlation (rho=0.78, P<.0001),
followed by pressure half-time (PHT: rho=0.66, P<.001), continuity equation (CE:
rho=0.61, P=.003), and 2D PISA (rho=0.26, P=.203). Bland-Altman analysis revealed
a good agreement for MVA estimation with 3D PISA (mean difference -0.03 cm2 ;
limits of agreement (LOA) -0.40-0.35), in contrast to wider LOA for 2D methods:
CE (mean difference 0.02 cm2 , LOA -0.56-0.60); PHT (mean difference 0.31 cm2 ,
LOA -0.32-0.95); 2D PISA (mean difference -0.03 cm2 , LOA -0.92-0.86).
CONCLUSIONS: MVA estimation using 3D PISA was feasible and more accurate than 2D
methods. Its introduction in daily clinical practice seems possible and may
overcome technical limitations of 2D methods.
PMID- 28517047
TI - SU-E-T-612: Hybrid-Input-Output Algorithm for IMRT Optimization with Dose-Volume
Histogram Constraints.
AB - PURPOSE: Dose-volume histogram (DVH) is a clinically relevant criterion to
evaluate a treatment plan quality. It is hence desirable to incorporate DVH
constraints in treatment planning process for intensity modulated radiation
therapy (IMRT). Yet, these constraints usually lead to difficulties due to their
non-convex nature. The purpose of this project is to solve the IMRT optimization
problem with DVH constraints using a hybrid-input-output (HIO) method. METHODS:
The IMRT optimization problem finds a dose distribution z under two constraints,
where the elements of the vector z are the dose value at each spatial coordinate.
First, there exist a corresponding fluence map x such that Dx=z and x>0, where D
is the dose deposition matrix. Second, the dose distribution z should satisfy the
DVH constraints. These two constraints define two sets of the dose distributions,
denoted by A and B, and the solution to the IMRT problem lies in the intersection
of these two sets. Our method finds the solution via the HIO algorithm that
iteratively updates the solution according to its projections onto the two sets
until convergence. The projection to A is handled by solving a least square
problem and the projection to B is achieved by gradually adjusting voxel doses
that validate the DVH criteria to meet the constraints. RESULTS: We have tested
our algorithm using 7-field IMRT plans for 4 prostate cancer cases. Clinically
relevant DVH constraints are considered for PTV, rectum, and bladder. In all the
cases, the algorithm is able to find the solutions that satisfy all the DVH
constraints. CONCLUSIONS: We have developed an algorithm to solve the IMRT
optimization problem with DVH constraints using the HIO approach. Tests conducted
in prostate cancer cases have demonstrated the effectiveness of our algorithm.
PMID- 28517045
TI - SET DOMAIN GROUP701 encodes a H3K4-methytransferase and regulates multiple key
processes of rice plant development.
AB - Chromatin-based epigenetic information plays an important role in developmental
gene regulation, in response to environment, and in natural variation of gene
expression levels. Histone H3 lysine 4 di/trimethylation (H3K4me2/3) is abundant
in euchromatin and is generally associated with transcriptional activation.
Strikingly, however, enzymes catalyzing H3K4me2/3 remain poorly characterized in
crops so far. Here, we investigated the function of the rice SET DOMAIN GROUP 701
(SDG701) gene by molecular and biochemical characterization of the gene product,
and by studying effects of its loss or gain of function on plant growth and
development. We demonstrated that SDG701 encodes a methytransferase specifically
catalyzing H3K4 methylation. Overexpression and knockdown experiments showed that
SDG701 is crucial for proper sporophytic plant development as well as for
gametophytic transmission that directly impacts rice grain production. In-depth
analysis of plant flowering time revealed that SDG701 promotes rice flowering
under either long-day or short-day photoperiods. Consistently, the SDG701 protein
was found to bind chromatin to promote H3K4me3 and to enhance expression of the
rice Hd3a and RFT1 florigens. Collectively, our results establish SDG701 as a
major rice H3K4-specific methyltransferase and provide important insights into
function of H3K4me3 deposition in transcription activation of florigens in
promoting plant flowering.
PMID- 28517049
TI - SU-E-T-616: Efficacy of Biological Dose Painting for Head and Neck Cancer.
AB - PURPOSE: Study the feasibility and planning robustness of a novel biological dose
painting approach prescribing biological effect instead of dose. METHODS:
Prescribed'effect maps' were generated using models relating FMISO-PET tracer
uptake to hypoxia reduction factors (HRF). HRFs decrease the LQ-model radio
response parameters a and beta and therefore the delivered biological effect. The
model is driven by four parameters (m, K, p50, Imax), whose values have been
determined through a comprehensive literature search. A planning study on ten
previously treated patients with oropharyngeal cancer was conducted. Dose-painted
plans were generated with the KonRad inverse planning system (DKFZ, Heidelberg).
Simulated FMISO-PET images were generated by defining clinically relevant hypoxic
sub-volumes within the GTV. Tracer uptake values were derived from various PET
imaging studies for head and neck cancer. Each treatment plan was developed in
four steps: 1) Simulate hypoxia tracer distribution in GTV. 2) Prescribe
biological effect. 3) Optimize dose-painted plan under the same normal tissue
constraints of the nominal clinical plan. 4) Conduct robustness analysis by
evaluation of the dose-painted plan for 27 parameters combinations of K, m, p50
(mean +/- 1SD). RESULTS: The predicted biological effect of clinical plans under
normoxic conditions overestimates the delivered effect due to decreased radio
sensitivity in hypoxic tumours. Biological dose painting compensates for hypoxia
by delivering a higher dose to hypoxic sub-volumes while still maintaining all
critical structure dose limits. Model parameter uncertainties clearly affect
robustness. The high uncertainty on p50 (pO2 for which tracer concentration is
half of maximum uptake) was found to cause the largest variations in the
delivered biological effect. CONCLUSIONS: Clinically acceptable dose-painted
plans can be generated without sacrificing the normal tissue constraints.
Planning robustness suffers from the high uncertainty on the p50 value. Improved
methods to determine the model parameters would be desirable. Financial support
provided by Ryerson University, Toronto, Ontario, Canada.
PMID- 28517048
TI - SU-E-T-571: Prostate IMRT QA: Prediction of the Range of Rectal NTCP Using a 2D
Field Approach Based on Variations of the Rectal Wall Motion and Thickness.
AB - PURPOSE: The aims of this study is to (1) introduce a 2D field of possible rectal
normal tissue complication probability (NTCP) in prostate intensity modulated
radiotherapy (IMRT) plan, so that based on a given prescribed dose the rectal
NTCP is merely a function of the rectal wall thickness and rectal motion; and (2)
separate the 2D field of rectal NTCP into area of low risk and area of high risk
for rectal toxicity < Grade II, based on the threshold rectal NTCP. METHODS: The
2D field of NTCP model was developed using ten randomly selected prostate IMRT
plans. The clinical rectal geometry was initially represented by the cylindrical
contour in the treatment planning system. Different combinations of rectal
motions, rectal wall thicknesses, planning target volume margins and prescribed
doses were used to determine the NTCP in prostate IMRT plans. RESULTS: It was
found that the functions bordering the 2D field for the given AP, LR and SI
direction can be described as exponential, quadratic and linear equations,
respectively. A ratio of the area of 2D field containing data of the low risk
NTCP to the entire area of the field was introduced and calculated. Although our
method is based on the Kutcher's dose response model and published tissue
parameters, other mathematical models can be used in our approach. CONCLUSIONS:
The 2D field of rectal NTCP is useful to estimate the rectal NTCP range in the
prostate pre-treatment and treatment QA. Our method can determine the patient's
threshold immobilization for a given rectal wall thickness so that prescribed
dose can be delivered to the prostate to avoid rectal complication. Our method is
also applicable to multi-phase prostate IMRT, and can be adapted to any treatment
planning systems.
PMID- 28517050
TI - SU-E-T-582: Assessment of Improved Critical Structure Sparing Using Biologically-
Based Optimization for Volumetric Modulated Arc Therapy of Head and Neck Cancer.
AB - PURPOSE: To investigate the critical structure sparing achievable by biological
optimization for modulated volumetric arc (VMAT) of head and neck (H&N) cancer.
METHODS: Ten H&N VMAT patients who were originally planned and treated with
simultaneous integrated boost technique using dose-volume based optimization,
were selected. For each patient, a new VMAT plan was generated using the
generalized equivalent uniform dose (gEUD)-based biological optimization
available in Pinnacle3 Smart Arc. While the objectives for targets were defined
in terms of minimum and maximum EUDs with 'a' values of -15 and +15, the critical
structure objectives were defined in terms of maximum EUDs with 'a' values of'1',
'5' and '10'. Both dose-volume and gEUD-based VMAT plans used 6MV, 280 degree
dual arcs. The prescription doses for all cases were 70Gy to PTV1, 60Gy to PTV2
and 54Gy to PTV3 delivered in 33 fractions. The critical structures included
cord, parotids, brainstem, and esophagus. The critical structure sparing in
physical and biological plans were assessed using dose- volume indices, including
D2, D50, and Dmean, and MUs and treatment delivery times. RESULTS: PTV coverage
obtained by both dose-volume and biological-based optimization were generally
very similar, although the target conformality was slightly better for dose
volume based VMAT plans. The gEUD-based plans produced superior critical
structure sparing, yielding up to 55% reduction in cord D2, 35% reduction in
parotids Dmean and 14% reduction in brainstem D2 as compared to dose-volume based
plans. On average, MUs for gEUD-based plans increased by 12.1%, 18.8% and 21.3%
for 'a' values of'1', '5' and '10' respectively compared to dose-volume based
VMAT plans with no change in delivery times. CONCLUSIONS: This study showed that
the biology-based optimization has ability to generate H&N VMAT plans with
significantly improved critical structure sparing with generally similar
target(s) coverage as compared to the dose-volume based physical optimization.
PMID- 28517051
TI - SU-E-T-593: VMAT Vs. IMRT for Treatment of Neoplasms of the Brain: Dosimetric
Quality and Delivery.
AB - PURPOSE: A retrospective study was performed to determine any dosimetric or
delivery benefits for treatment planning with intensity-modulated radiotherapy
(IMRT) versus volumetric-modulated arc therapy (VMAT) for the treatment of brain
neoplasms. METHODS: Eighteen patients treated with modulated brain radiotherapy
treatments were included in this study (primary treatment volumes of 15.3 to
374.9 cc). IMRT and VMAT plans were generated for each patient using the same
criteria for prescription coverage and normal tissue sparing. IMRT optimizations
ranged from five to seven fields and VMAT from two to four arcs. Plans were
generated with Varian Eclipse treatment planning system utilizing AAA-8615 dose
calculation algorithm. RESULTS: VMAT optimizations provided limited dosimetric
advantages versus IMRT. VMAT provided superior treatment volume coverage (volumes
receiving 95%, 100% of prescription dose (V95%, V100%)) over IMRT, but
differences were not statistically significant (paired t-test p > 0.05). Relative
maximum dose values, conformity and homogeneity indices also exhibited no
statistical differences. IMRT plans resulted in similar mean brain minus
treatment volume (Brain- TV) dose (mean = 1460.1 vs. 1506.3 cGy; p = 0.056). The
volume of Brain- TV receiving 40Gy was lower for VMAT than IMRT (average = 38.96
vs. 44.97 cc; p = 0.050). Maximum skin dose was lower for VMAT (mean = 4568.8 vs.
5063.3cGy; p = 0.006), as well as skin V20Gy (6.56% vs 7.69%; p = 0.027) and
V40Gy (0.56% vs. 0.35%; p = 0.017). VMAT plans required fewer fields along with
fewer MU than IMRT (mean = 388.2 vs. 721.1 MU, respectively), allowing for
approximately 20% faster delivery times. CONCLUSIONS: VMAT treatments
significantly reduced treatment time due to reduced MU and fewer fields. Certain
skin and Brain-TV high dose spread parameters were superior for VMAT as compared
to IMRT plans. All other dosimetric parameters tested were statistically
equivalent for VMAT and IMRT techniques.
PMID- 28517052
TI - SU-E-T-564: Radiation Therapy for Lung Cancer: A Treatment Planning Comparison
among Fixed Field IMRT, Coplanar and Noncoplanar Arcs Volumetric Modulated Arc
Therapy.
AB - PURPOSE: A treatment planning study was performed to compare fixed field IMRT,
coplanar and noncoplanar VMAT. METHODS: Treatment planning CT scans of three lung
cancer patients with small (2244cc), medium (2845cc) and large (3531cc) lungs
were used to create simulated patient cases. For each simulated patient, three
spherical tumors (GTV) of varying diameters: 1, 3, 5 cm were contoured onto lung
CT scans. The ITV was set as GTV+2 cm and the PTV was set as ITV+1 cm. The
location of the tumor was set in the right middle lobe of lung. For each patient
scenario, the IMRT (nine static fields), single coplanar arc VMAT and 5
noncoplanar arcs VMAT treatment plans were generated using Pinnacle treatment
planning system. The arcs of noncoplanar VMAT were set at -30 degrees (clockwise
and counterclockwise), 0 degrees and 30 degrees (clockwise and
counterclockwise). Thetreatment plans were evaluated by calculation of V100%,
V80%, V50% and V20%, DVH of dose constrain rings (DCR) at PTV+1cm, +2cm, +3cm,
+4cm and Paddick Conformity Index (CI: 0-1 best) and Gradient Index (GI:the
smaller the better). RESULTS: The V100% and V80% were similar for all the plans
but the V50% and V20% were the largest for IMRT, and the smallest for noncoplanar
VMAT. The noncoplanar VMAT had larger V<20but smaller V>20 for all the DCRs
comparing to the other two plans. The CI of noncoplanar VMAT was slightly larger
than the other two plans. The GI was the smallest for noncoplanar VMAT and the
largest for IMRT for all the simulation scenarios. CONCLUSIONS: The noncoplanar
VMAT consistently provides high dose conformity to the target and low dose to
healthy tissue. The noncoplanar VMAT has larger low dose volume while smaller
high dose volume comparing to IMRT and coplanar VMAT.
PMID- 28517053
TI - SU-E-T-604: Inter Planner Dosimetric Variations in IMRT.
AB - PURPOSE: To study inter-planner variations in IMRT dosimetry with identical dose
prescription in IMRT optimization for estimation of quality of treatment plans by
using dose volume histogram (DVH). METHODS: Five treatment planners: p1, p2, p3,
p4 and p5 with Eclipse TPS and Varian accelerator were chosen. The 3D data sets
including PTV and OAR of a prostate case was sent with instructions for beam
orientations, energy and dose-volume constraints. Each planner performed the
treatment planning process with inhomogeneity corrections by using the same dose
constraints. DVH and isodose distributions were compared to examine the inter
planner variations. RESULTS: There were large variations in the IMRT plans
reflected by the DVH among the planners even with identical dose constraints in
IMRT optimization. Clinically constraint#1 (D95-V95) dose criteria could be
considered as the most important one. Two planners did not meet the criteria,
whereas planner 4 met all of the dose criteria for PTV and OARs. The inter
planner variations in PTV as large as 20% were found in this study. Every time
optimization is performed even with the same constraints, the DVH output was
significantly different due to the differences in constraint weights.
CONCLUSIONS: There exists a significant inter planner variation for all cases
studied indicating that even for the same constraints the outcome cannot be
guaranteed to be identical due to cost function convergence. It seems feasible to
control the over-dosage for all planners. However we see large deviations in
plans with respect to different constraints. Planner 4 met all the dose criteria
for PTV and OARs indicating that it is possible to plan and meet all the dose
criteria. This approach could be used as gold standard.
PMID- 28517054
TI - SU-E-T-575: To Analyze the Clinical Impact of Esophageal Sparing on Treatment
Plans for Patients with Grade 3 Esophagitis.
AB - PURPOSE: To analyze the clinical impact of esophageal sparing on treatment plans
for patients with grade 3 esophagitis. METHODS: The treatment plans of 8 patients
(project total: 20 patients) who were treated with IMRT and exhibited stage 3
esophagitis were re-planned to give a simulated clinical plan with dose
distribution that mirrored our current clinical practice (74Gy to the target, and
5mm margins), and a plan that emphasized esophageal sparing. Doses to the
esophagus, heart, cord, lung and PTV were compared. RESULTS: Comparing the
esophageal sparing plan to the simulated clinical plan, the mean reduction in
esophageal volume receiving 50, 55, 60, 65, and 70Gy were 2.0, 3.2, 5.0, 7.2, and
10.9 cm3 , respectively. The mean reduction in the continuous length of esophagus
receiving 50, 55, 60, 65, and 70Gy were 12, 24, 38, 40, and 47mm, respectively.
The associated reduction in dose to 90% and 95% of the PTV was 2.2 and 3.8Gy,
respectively. Of the 8 patients examined, 2 showed a significant decrease in PTV
coverage (4.6Gy, 12.3Gy for 90% of PTV), 4 showed decreases under 1.1Gy, but 2
showed an increase of 1.4Gy and 0.5Gy for 90% PTV. Cord dose was maintained below
50Gy, and there was a slight increase in mean heart dose and mean lung dose of
2.4Gy, and 2.7Gy, respectively. Data will also be presented comparing these plans
with the actual treated plans (for which the patients had grade 3 esophagitis)
and plans that emphasize PTV coverage. CONCLUSIONS: Treatment planning to
emphasize esophageal sparing can reduce the volume and continuous length of the
esophagus which receives high doses. There is some associated modest reduction in
PTV coverage. In summary, in many cases esophageal sparing can be accomplished
for lung cancer cases while maintaining adequate PTV coverage, although there is
variability between patients.
PMID- 28517055
TI - SU-E-T-586: Comparison between CT-and FLT-PET-Defined Target Volumes and
Dosimetry for Radiotherapy Planning in Esophageal Carcinoma.
AB - PURPOSE: To study the advantage of fused 3-deoxy-3-18F-fluorothymidine (FLT)
positron emission tomography (PET) and computed tomography (CT) images on
radiotherapy planning for esophageal carcinoma patients . METHODS: Ten patients
with esophageal carcinoma were referred for radiotherapy. Each patient underwent
CT and FLT PET scan for simulation plan in the same treatment position. FLT PET
images were coregistered with CT images. GTVCT was initially performed on CT
images, GTVPET-CT were automatically segmented on FLT PET/CT images using a fixed
threshold values at 1.4. Two kinds of treatment plans were designed based on
GTVCT and GTVPET-CT. The radiation dose was prescribed as 60 Gy in 30 fractions.
The dose-volume parameters of target volume and normal tissues, CI and HI of
based on the GTVPET- CT and GTVCT were compared. RESULTS: The mean GTV delineated
on CT and PET- CT were 39.28 cms and 34.48 cms , respectively . The values for
mean lung dose, total-lung volume receiving =5, = 10, = 20 and = 30Gy;mean heart
dose, heart volume receiving =30Gy and normal tissues of plan based on the GTVPET
CT were significant lower than plan based on the GTV-CT. CONCLUSIONS: In our
study, FLT PET use has an impact on target delineation for radiotherapy planning.
GTVPET-CT is significantly smaller than GTVCT with a mean volume reduction of
16%. CT and FLT/PET image fusion appeared to have an advantage on dose reduction
of organ at risk in radiotherapy planning of esophageal carcinoma.
PMID- 28517056
TI - SU-E-T-597: Influence of Smoothing Parameters on Dynamic IMRT Plan Quality and
Deliverability.
AB - PURPOSE: To study the impact of different smoothing parameters on IMRT plan
quality and deliverabilityMethods: Five previously treated patients of carcinoma
cervix were chosen. Planning target volume (PTV) and organ at risk (OAR) i.e.
bladder and rectum were contoured. In each case, five different dynamic IMRT
plans with 6MV photon beam were created in eclipse TPS for Varian 2300C/D linear
accelerator. During optimization, dose volume constraints and priorities were
kept constant and smoothing parameters were varied as follows: 10/5, 40/30 (TPS
default value), 80/60, 100/80 and 200/150 in x/y direction. Total dose was
5040cGy in 28 fractions and prescribed at 95% isodose. Plan quality was analyzed
by means of coverage index (CI=PTV covered by prescription dose/PTV), OAR mean
doses and total monitor units (MUs) required to deliver a plan. In each case,
deliverability of treatment plans were verified with I'matriXX ion-chamber array
and compared with TPS dose-plane using gamma index of 3% dose difference and 3mm
distance to agreement criteria. RESULTS: The CI values were 0.9435+/-0.032,
0.9418+/-0.034, 0.9380+/-0.041, 0.9330+/-0.047 and 0.8681+/-0.072 for 10/5,
40/30, 80/60, 100/80 and 200/150 in x/y direction. PTV dose maximum decreases
with the increase of smoothing parameters and values were 5724.38+/-106.08
5723.30+/-131.60, 5708.44+/-1 16.74, 5697.92+/-116.82 and 5587.50+/-189.50cGy.
The bladder mean doses were 4027.46+/-630.40, 3821.62+/-420.62, 3819.58+/-427.08,
3813.42+/-435.02 and 3814.78+/-438.0cGy. Rectum mean doses were 3839.88+/-466.02,
3835.52+/-473.18, 3837.52+/-472.88, 3839.10+/-471.20 and 3918.94+/-469.76cGy.
Similarly, Total MUs were 1588+/-205, 1573+/-214, 1513+/-274, 1456+/-335 and
1219+/-68. Gamma pass rate increases with the increase of smoothing parameters
and values were 99.16+/-0.21%, 99.07+/-0.19%, 99.24+/-0.28%, 99.29+/-0.29% and
99.75+/-0.15%. CONCLUSIONS: When smoothing parameters decreased below TPS default
value, plan quality increases, but deliverability decreases. If smoothing
parameters increased above TPS default value, deliverability increases but plan
quality decreases. Total MU decreases with the increase of smoothing parameters.
Therefore, it's a trade-off between plan quality and deliverability which needs
to be justified clinically.
PMID- 28517057
TI - SU-E-T-568: Hippocampus and Neural Stemcell Sparing Using Proton Therapy in Whole
Brain Irradiation.
AB - PURPOSE: To investigate feasibility of using proton therapy (PT) in neural
stemcell sparing and to compare its dosimetric advantage to IMRT. To investigate
the robustness of the proton plan in hippocampus sparing by introducing
translation and rotation errors in treatment plan. METHODS: Hippocampal
neurogenesis directly correlates to memory and other cognitive functions.
Compared to the traditional whole brain (WB) uniform irradiation, Photon
Intensity-Modulated-Radiation-Therapy (IMRT) can reduce hippocampal dose somewhat
but limited by its beam exit dose. Pinnacle and Eclipse were used, respectively,
for IMRT and PT planning (30Gy in 10 fractions) for hippocampal neural stemcell
sparing WB irradiation. Both hippocampus and neural stemcell regions were
contoured as avoidance region. Similar to RTOG0933, the target was defined as the
WB subtracted by 5 mm expansion of the avoidance region. Other organs-at- risk
(OARs) includes lenses, eyes, optical chiasm, optical nerves, brainstem and
parotids. Twelve coplanar beams were used in IMRT plans with 2.5mm MLC width.
Objectives were specified to maximize target coverage and reduce dose to
avoidance region and to other OARs. There were 9 non- coplanar proton beams that
include 2 pairs of patch fields, 1 pair of match fields and 4 open fields. Distal
blocking was used in 5 beams. RESULTS: Both plans' target coverage was scaled at
70% target covered by 30Gy. Plan comparison between proton and IMRT are,
respectively, as follows: Target D2 (36.2, 37.3Gy); Mean dose to avoidance region
(0.96, 5Gy); mean doses to left-lens (0.21, 3.35Gy); mean doses to right-lens
(0.25, 3.57Gy); mean dose to left-parotid (0.82, 9.57Gy) and right-parotid (0.11,
11.6Gy). Similar dose distribution found in brainstem, eyes and optical nerves
and chiasm for both proton and IMRT plans. CONCLUSIONS: Proton plan demonstrated
dosimetric advantage in neural stemcell and hippocampus sparing than IMRT plan.
The proton plan is robust from translation and rotation setup errors.
PMID- 28517058
TI - SU-E-T-608: Integrated Beam Orientation and Fluence Map Optimization in Radiation
Therapy Treatment Planning.
AB - PURPOSE: To efficiently select high-quality coplanar or non-coplanar beam
orientations for IMRT treatments while formally and explicitly incorporating the
effect of the selected beam orientations on the quality of the dose distribution
obtained by the treatment plan optimization model. METHODS: Beam orientation
models consider a discrete set of potential coplanar and/or non-coplanar beam
locations around the patient. A new greedy algorithm is proposed to solve a model
that integrates beam orientation optimization (BOO) and fluence map optimization
(FMO). The algorithm iteratively adds beams to a FMO model. In each iteration, an
attractiveness measure is associated with each remaining candidate beam
orientation. This attractiveness measure is based explicitly on an optimal dose
distribution that allows only the currently selected set of beams to be used.
Several alternate attractiveness measures are considered which use either first
order information or both first and second-order information. Performance of the
algorithm was assessed on a clinical lung cancer case. RESULTS: The developed
beam selection algorithm was applied to a lung cancer case using either coplanar
beams or both coplanar and non-coplanar beams. In the coplanar case, beam
orientations were found that produce a superior dose distribution to that using
an equal number of equi-spaced beams. In the non-coplanar case it was found that
fewer beams were needed to produce a dose distribution of comparable quality to
that found in the coplanar case. CONCLUSIONS: The developed solution approach
showcases the potential benefits of integrating different steps in the treatment
plan optimization process. By integrating the BOO and FMO models, treatment plan
quality was explicitly incorporated into the beam selection process. BOO can be
automated and implemented efficiently, which eliminates the guesswork involved in
manually adjusting beam orientations in IMRT treatment planning.
PMID- 28517059
TI - SU-E-T-579: Dosimetric Benefits of Online Adaptive Replanning for Post-Operative
Radiation Therapy of Prostate Bed.
AB - PURPOSE: To demonstrate the dosimetric benefits of using an online adaptive
replanning scheme to address interfractional variations in radiotherapy of
prostate bed. METHODS: We have previously developed an online adaptive replanning
tool (RealART, Prowess Inc.) aiming to address interfractional variations
including organ deformation and rotation. Using this tool, we analyzed a total of
102 daily pre-treatment CTs acquired using an in-room CT (CTVision, Siemens) for
10 patients treated with post-operative IMRT of prostate bed. The PTV was assumed
to be the volume enclosed by the 95% prescription isodose surface generated for
the conventional four field box. On each daily CT set, contours of the PTV,
rectum and bladder were generated by populating the planning contours using an
auto-segmentation tool based on deformable registration (ABAS, Elekta) with
manual editing. Four plans were generated and compared: (1) IGRT (repositioning)
plan by copying the original plan with aligning the anterior rectal wall from the
daily CT to that of the planning CT, (2) IGRT plan by copying the original plan
with aligning the surgical clips, (3) online adaptive plan by tailoring the
original plan to conform to the anatomy of the day, and (4) a new plan re-
optimized based on the daily anatomy. RESULTS: The adaptive and re- optimization
plans are in general superior than the two repositioning plans in terms of both
target coverage and critical structure sparing. For example, the averages of dose
volume quantities for all daily CTs are: rectum V45Gy 55.7+/-18.0% (one standard
deviation), 57.3+/-17.5%, 48.2+/-11.8%, 42.5+/-9.6%; rectum V60Gy 31.8+/-20.3%,
34.0+/-16.6%, 22.6+/-9.7%, 16.5+/-7.4%; bladder V45Gy 30.0+/-11.9%, 39.5+/-24.2%,
37.6+/-16.8%, 36.5+/-16.2%; bladder V60Gy 17.4+/-9.2%, 25.4+/-18.1%, 24.7+/
12.7%, 23.9+/-12.0%; PTV V100 81.9+/-16.6%, 88.7+/-7.9%, 92.9+/-4.6%, and 94.6+/
2.4% for the above (1)-(4) plans, respectively. CONCLUSIONS: The online adaptive
replanning scheme is effective to account for interfractional variations in post
operative radiotherapy of prostate bed. This work is supported partially by MCW
Cancer Center Fotsch Foundation.
PMID- 28517060
TI - SU-E-T-590: Procedure for Verification and Inter-Comparison of IMRT Beam Models.
AB - PURPOSE: The implementation of an accurate beam model is an integral part of the
commissioning of any planning system. This process is especially challenging in
the case of IMRT beam models owing to the complexity of small field sizes and MLC
leaf-end and tongue-and-groove effects. The question of how to judge the quality
of an IMRT beam model in comparison with other versions of the same model is
central to this work. METHODS: We make an important distinction between
evaluation of the beam model and evaluation of the optimization routine that is a
part of any IMRT planning system. The H-shaped target used in this work has
several important features: it can only be covered by segments with small field
size, for which all leaf design effects are important, and it has the overall
dimensions of a common IMRT target. The procedure for inter-comparison of two
IMRT beam models (old and new) involves the generation of two plans optimized
with each beam model using identical IMRT prescriptions. Both plans are
subsequently delivered on a solid water phantom with film located in two parallel
planes with a small-volume ionization chamber inserted in the center. RESULTS:
Four dose calculations are performed, such that each plan is calculated with
either of the two beam models. The four dose distributions are subsequently
compared with the two film measurements using gamma analysis. In addition, the
absolute dose measured in the center of the dose distribution is compared with
the calculated value. A score is assigned to each beam model based on the
results. CONCLUSIONS: Using the procedure outlined in this presentation,
different versions of an IMRT beam model can be compared and scored for quality.
Adoption of a unified strategy for beam model inter-comparison can greatly
facilitate the evaluation and commissioning of IMRT beam models.
PMID- 28517061
TI - SU-E-T-611: Utilizing Machine Learning Techniques for Beam Angle Selection in
Radiation Treatment Planning.
AB - PURPOSE: To utilize machine learning techniques within beam angle optimization to
determine an optimal Intensity-modulated radiation therapy (IMRT) beam angle set.
METHODS: The input data were derived from a collection of equally-spaced seven
beam plans (e-plans) generated using the Pinnacle. This collection of e-plans
contains all 72 beam angles corresponding to 5 degree spacing, and the dose
delivered to patient tissues from each of these 72 angles was extracted to
generate p-scores. Equally-spaced beam sets are commonly used in clinical
practice, so this set of plans not only provides initial input data for our beam
angle selection (BAS) procedure, but also provides a good set of benchmarks
against which treatment improvement may be measured. A beam set scoring function
was developed based on a weighted sum of overdose/underdose criteria. The Nested
Partitions (NP) global optimization framework is then utilized to guide a sample
based search for the global optimal of the beam angle space. In our NP-based
approach to BAS, a single sample is a 7-beam set satisfying beam spacing
constraints. A fast scoring method based on the e-plan single-beam dose data was
used to obtain an initial approximate score (c-score) and a set of dose component
scores for each beam set. Machine learning techniques were then employed to
predict each dose component, and these values were used to compute a predicted
score. RESULTS: The average improvements in p-scores for 5 cases were 43%, 29%
and 11% comparing to default eplan, best eplan and conventional NP (without ML).
10%, 12% and 15% improvement was achieved for sparing of spinal cord, brain stem
and oral mucosa, respectively. CONCLUSIONS: Machine learning tools provide an
effective technique for rapid high-quality approximate scoring for beam angle
sets in IMRT. This approximation process leads to excellent beam sets when
embedded within the NP global optimization framework. This work was supported in
part by a grant from the NIH/NCI CA130814.
PMID- 28517062
TI - SU-E-T-615: Quantifying the Benefit of Adaptive Fractionation.
AB - PURPOSE: To quantify the benefit of adaptive fractionation, through both
theoretical test cases and patient data. METHODS: We consider the effect of
delivering a different fraction size based on the changes observed in the patient
anatomy. Given that a fixed prescription dose must be delivered to the tumor over
the course of the treatment, we find that adaptively varying the fraction size
results in a lower cumulative dose to a primary organ-at-risk (OAR). We construct
a one dimensional theoretical example by randomly varying the distance between
the tumor and OAR, and simulate the benefit of adaptive fractionation in such a
setting. Next, we test our methodology using contoured daily CT images from 5
prostate patients. RESULTS: For the theoretical example, we found about a 10%
decrease in dose to the OAR when using a uniformly distributed motion model and a
20% daily fraction size deviation. In general, the amount of decrease in dose to
the OAR varied significantly (5-85%) for these theoretical test cases depending
on the amount of motion in the anatomy, the number of fractions, and the range of
fraction sizes allowed. Preliminary results from the prostate patients indicate
an average reduction in dose to the rectum of 1.4%, 3.5%, and 7.0% when using
20%, 50%, and 100% daily fraction size deviations, respectively. CONCLUSIONS:
Qualitatively, the theoretical example indicates that adaptive fractionation is
beneficial for disease sites in which there is significant inter-fractional
motion. We also expect greater benefit when using many fractions and allowing for
large daily fraction size deviations. For the prostate disease site in
particular, we find that adaptive fractionation is beneficial only when allowing
large daily fraction size deviations. Further research quantifying the gain for
disease sites that exhibit significant inter-fractional motion, such as rectal
and cervical cancers, would be useful. Partially supported by Siemens.
PMID- 28517063
TI - SU-E-T-581: Planning Evaluation of Step-And-Shoot IMRT, RapidArc and Helical
TomoTherapy for Hippocampal-Avoidance Whole Brain Radiotherapy (HA-WBRT).
AB - PURPOSE: Several planning strategies are available for hippocampal- avoidance
whole-brain radiotherapy (HA-WBRT) following RTOG protocol 0933, but have yet to
be compared on a common set of patient data. In this inter-institutional
investigation, we evaluate three modalities likely to be employed by protocol
participants; step-and-shoot IMRT, volumetric modulated arc therapy, and helical
tomotherapy. A common set of patients is used for comparison, including
credentialing and successfully accrued patients. METHODS: Eight patient datasets
were selected and de-identified prior to planning. Structures were contoured by
physicians per protocol using fused MRI datasets. Three plans were generated for
each dataset: Philips Pinnacle 9-field non-coplanar IMRT using protocol
recommended beam parameters, Varian's RapidArc using two coplanar arcs, and
Accuray's TomoTherapy using a 1cm jaw width. With the goal of meeting the
compliance criteria outlined in RTOG 0933 (target coverage and dose limits to the
hippocampus and optic structures), three planners independently planned each
modality without prior knowledge of the patient's other plans to reduce bias. The
three plans for each patient were compared according to the protocol's dosimetric
compliance criteria. A homogeneity index was also computed to compare target dose
uniformity. RESULTS: All plans achieved the protocol dose criteria, except for
one RapidArc plan with slightly inferior dose to the optic chiasm. TomoTherapy
offered superior dose homogeneity for all patients. For the two linac based
methods, RapidArc was found to provide dose homogeneity at least as good as, and
in most cases superior to, 9-field step-and-shoot IMRT. CONCLUSIONS: Helical
TomoTherapy offers superior dose homogeneity for HA-WBRT following RTOG 0933.
Compared to step-and-shoot IMRT, volumetric modulated arc techniques, such as
RapidArc, can offer improved homogeneity for HA- WBRT and are generally more
efficient/expeditious to deliver than the noncoplanar 9-field arrangement
recommended by the protocol, which uses 7 separate couch angles.
PMID- 28517064
TI - SU-E-T-592: Comparison of Low Dose Volume and Integral Dose in Rotational Arc
Radiation Therapy Modalities.
AB - PURPOSE: To compare low dose volume and integral dose of various rotational arc
radiation therapy modalities, including helical tomotherapy (HT) and other
volumetric modulated arc therapies (VMAT). METHODS: A digital cylindrical phantom
and an anthropomorphic pelvic phantom were used in the study. HT treatment was
planned on TomoTherapy Planning Station (Accuray) and VMAT plans were generated
on Pinnacle (Philips) and Eclipse (Varian). Same objectives and criteria were
used for all the planning tasks. Tomotherapy plans were made with both 1cm jaw
and 2.5cm jaw. Pinnacle SmartArc and Eclipse RapidArc plans used 1 arc and 2
arcs. Plan quality was evaluated by dose-volume histograms, conformity index
(CI), and heterogeneity index (HI). V10% and V20% of body were used in
quantifying low dose volume. Integral doses were computed for each plan and
compared. Dose profiles across the target center were retrieved to show the rate
of dose falls off. RESULTS: All arc TPS generated clinically acceptable plan with
comparable target CI and HI. The V20% of body of the cylindrical phantom case
were 3551cc, 4054cc, 3375cc, 3438cc, 3714cc and 3679cc for tomotherapy 1 cm and 2
cm jaw, SmartArc 1 arc and 2 arc, and RapidArc 1 arc and 2 arc plans,
respectively. The integral doses were 19.67, 22.78, 18.68, 18.50, 19.78 and 19.73
Joule, respectively. For the anthropomorphic phantom, the integral doses were
81.69, 102.77, 84.5 and 82.5 Joule for tomotherapy 1cm, 2cm, SmartArc 1arc and
RapidArc 1arc, respectively. Dose profiles showed tomotherapy 1cm plan had
similar longitudinal penumbra as SmartArc and RapidArc, while tomotherapy 2.5cm
plan produced significant broader penumbra. CONCLUSIONS: Similar low dose volume
and integral dose are found in SmartArc, Rapid Arc, and as well as helical
tomotherapy plan of 1cm jaw. Tomotherapy plans of 2.5cm jaw, however, shows
higher low dose volume and integral dose.
PMID- 28517065
TI - SU-E-T-563: Which is More Important in IMRT Planning: The Number of Beam Angles
or the Number of MLC Segments?
AB - PURPOSE: Rotational IMRT delivery has attracted considerable attention. Some
people believe that rotational IMRT should provide better plan quality with more
beam angles to irradiate the target. In this work, we will study the impact of
the number of fields and MLC segments on the IMRT plan quality. METHODS: The RPC
IMRT benchmark phantom was used in the IMRT planning. The number of gantry angles
used ranges from 3 to 90 with various numbers of segments. All IMRT plans were
created using Pinnacle3 DMPO module using the same objectives. The final
objective value is used to quantify the plan quality. RESULTS: When the number of
beam angles is more than 3, the objective value decreases dramatically with
increasing segments till the number reaches around 60. When the number of
segments is small, the availability of more beam angles can clearly improve the
IMRT plan quality. However, such a plan quality improvement becomes less dramatic
as the number of total segments increases. For example, when the number of
segments is 30, increasing the number of beam angles from 3 to 18 can reduce the
objective value by 75%. Such a reduction reduces to 44% when the number of
segments increases to 60. Single-arc VMAT plans showed less desirable plan
quality comparing to fixed-field IMRT plans using the same number of beam-angles
and segments. CONCLUSIONS: The number of segments has dramatic impact on the IMRT
plan quality when the number of fields is more than 5. If enough segments are
used in IMRT planning, increasing the number of beam angles can only slightly
improve the plan quality. The increase in plan quality led by increasing beam
angles can be limited by the MLC motion constraint for rotational IMRT delivery.
PMID- 28517066
TI - SU-E-T-603: Influence of PTV Delineation at Air Cavity Interface on Tomotherapy
Plan Quality.
AB - PURPOSE: To determine if different ways in PTV delineation at an air cavity
interface yield differences in overall plan quality and treatment efficiency
Methods: Three different PTVs were used for treating a patient whose CTV
surrounded a large air cavity created by a resected hard palate. The CTV lined
the surface of the air cavity while PTV1 included the entire air cavity, PTV2
extended 4mm from the surface of the cavity into air, and PTV3 was reduced 4mm
within the surface of the cavity. Tomotherapy plans were generated for all three
PTVs. During each planning, all constraints to target and normal structures were
kept constant along with the number of optimizations. Same planning process was
repeated on a head and neck digital phantom with mock target, normal structures
and cavity. RESULTS: Three treatment planning approaches showed no significantly
different target coverage in terms of minimum or maximum dose to their respective
PTVs. All plans attained 95% coverage of the CTV and PTV by 100% of the
prescription. The conformity index (CI) of the plans delivered to PTV1, PTV2, and
PTV3 were 1.09, 1.11, and 1.18, respectively. The skin, optic nerves, brainstem
and spinal cord all received similar maximum dose to their respective volumes for
each plan within 1Gy. The monitor units required for each treatment plan were all
within 6% of one another with PTV1 having the highest. For head and neck phantom,
the CIs of three plans were 1.05, 1.21, and 1.18, respectively. The coverage of
the phantom CTV and sparing of normal structures were nearly equivalent. The
total treatment times were identical. CONCLUSIONS: Tomotherapy planning is able
to deliver dose to a head and neck PTV containing a large air cavity without
compromising target coverage, sparing of normal tissues, or delivery time.
PMID- 28517067
TI - SU-E-T-574: Volumetric Modulated Arc Therapy for Prostate Radiation: A Dosimetric
Comparison between VMAT Techniques and Fixed-Beam IMRT.
AB - PURPOSE: To compare prostate radiation planning using four VMAT techniques and
IMRT on plan quality and dose delivery efficiency. METHODS: The four VMAT
techniques are: 1) Monaco VMAT (Version 2.03.01, CMS Inc., MO); 2) RapidArc
(Eclipse Version 10.0, Varian Medical System Inc., CA); 3) SmartArc (Pinnacle
Version 9.0, Philips Radiation Oncology Systems, WI) and 4) helical TomoTherapy
(TomoTherapy Version 3, Accuray Inc., CA). The IMRT planning employed 7-field
fixed gantry on Pinnacle. Single full-arc plan using each technique was generated
for five prostate cases. All plans were prescribed to 70 Gy (2.5 Gy/fx) to 95%
PTV using 6 MV photon beams to achieve same PTV coverage and similar OAR sparing.
The quality of dosimetric plans was evaluated using metrics: target coverage,
heterogeneity index (HI), target/organ mean/max/min doses, EUD, dose-volume
histogram, etc. RESULTS: All VMAT plans are capable of delivering adequate target
dose with equal or better OAR sparing than IMRT plans. The average mean PTV doses
were 72.8, 73.1, 71.0 and 72.5 Gy with HIs of 1.10, 1.08, 1.03 and 1.05 for the
Monaco, RadipArc, SmartArc and TomoTherapy plans respectively. In low dose range,
TomoTherapy resulted in the highest V10 and V20 while V70 and V60 were generally
lower compared to other plans. Generated on the same platform, the SmartArc plans
were slightly more conformal (CI=1.04 vs 1.08) and less heterogeneous (HI=1.02 vs
1.04) with better OAR sparing compared to IMRT plans. The average required MUs
were 817 (Monaco), 735 (RapidArc), 798 (SmartArc) and 4986(TomoTherapy), compared
to 876 MUs for the IMRT plans. CONCLUSIONS: All single-arc VMAT techniques under
study improve normal tissue sparing with more efficient dose delivery compared to
prostate IMRT plans. RapidArc plans require least MUs while SmartArc provided
most homogenous plans. All VMAT plans demonstrate significantly reduced MUs to
achieve comparable dosimetric plans compared to Tomotherapy.
PMID- 28517069
TI - SU-E-T-596: Choroidal Metastases Irradiation with Volumetric Modulated Arc
Radiotherapy.
AB - PURPOSE: Intraocular metastases are present in up to 10% of patients with
systemic malignancies. With tumor cells spreading hematogenously, the posterior
choroid is frequently involved because of its rich vasculature. We treated a
woman who developed bilateral choroidal metastases from breast cancer. For the
patient, we designed three radiotherapy techniques. The study was to find the
dosimetric differences between them. METHODS: For the patient with bilateral
choroidal metastases, three-dimensional conformal radiotherapy (3D-CRT), inverse
intensity-modulated radiotherapy (IMRT) and volumetric modulated arc radiotherapy
(V-MAT) plans were designed. The prescription dose was 60 Gy in 30 fractions. The
dose distribution in the target, the dose to the organs at risk, total MU and
delivery time were compared. RESULTS: In 3D-CRT, IMRT and V-MAT plans, the volume
of target in 100% prescription dose were 92.5%, 93.3% and 92.0% respectively. V
MAT plan showed the best conformity and homogeneity in target. IMRT plan showed a
better homogeneity than 3D-CRT plan. In 3D- CRT, IMRT and V-MAT plans, the max
doses on left lens were 975.3 cGy, 739.9cGy, 870.2 cGy respectively. The max
doses on right lens were 929.9 cGy, 802.9 cGy and 889.0 cGy respectively. V-MAT
plan showed the lowest value for the max dose on left optic nerve and the lower
value for the right one compared to 3D-CRT plan. The MUs were 386, 973, 709 and
the delivery times were 10 min, 14min and 1.6 min respectively in 3D-CRT, IMRT
and V-MAT. V-MAT could significantly reduce the delivery time. CONCLUSIONS: V-MAT
plan showed the best conformity and homogeneity in target. IMRT showed the lowest
value in the max doses to lenses though the delivery time was longest. Overall, V
MAT showed a similar or better dose distribution, and most importantly, improved
treatment delivery efficiency. With the results, V-MAT technology could be
expected to choroidal metastases.
PMID- 28517068
TI - SU-E-T-585: Application of IMAT in Non-Small-Cell Lung Cancer with Simultaneously
Integrated Boost Radiation Therapy.
AB - PURPOSE: To compare and analyze the characteristics of intensity-modulated arc
therapy(IMAT) versus fixed-gantry intensity-modulated radiotherapy(IMRT) in
treatment of non-small-cell lung cancer. METHODS: Twelve patients treated in our
radiotherapy center were selected for this study. The patient subsequently
underwent 4D-CT simulation.Margins of 5 mm and 10mm were added to the ITV to
generate the CTV and PTV respectively. Three treatment plans (IMRT,one single arc
(RA1),double arcs (RA2))were generated with Eclipse ver.8.6 planning systems.
Using a dose level of75Gy in 15fractions to the ITV,60Gy in 15fractions to the
CTV and 45Gy in 15fractions to the PTV respectively. The target and normol tissue
volumes were compared, as were the dosimetry parameters. RESULTS: There were no
significant differences in CI of ITV,PTV, HI of ITV,CTV and PTV,
V5,V10,V15,V20,V25,V30,V45,V50 of total-lung and mean lung dose (all p>0.05).
However, the differences were significant in terms of CI of CTV, V5 of B-P (all
p<0.05). On the MU, IMRT=1540MU,RA1=1006 MU and RA2=1096 MU. (F=12.00,P=0.000).On
the treatment time, IMRT= 13.5min,RA1= 1.5min, and RA2=2.5 min (F=
30.11,P=0.000). CONCLUSIONS: IMAT is equal to IMRT in dosimetril evaluation. Due
to much less Mu and delivery time,IMAT is an ideal technique in treating patients
by reduceing the uncomfortable influnce which could effect the treatment.
PMID- 28517070
TI - SU-E-T-567: Improve Dose Conformity with IMRT Using Shorter Source to Tumor
Distance.
AB - PURPOSE: To reduce the potential of late toxicity (tissue necrosis and cognitive
function loss) from brain radiotherapy, we studied a novel planning technique for
MLC-equipped linear accelerators (LINACS) that reduces the high doses delivered
outside the PTV, enhancing radiation dose conformity. METHODS: The feasibility of
improving dose conformity by using variable source-to-tumor distances was tested
on brain CT datasets with tumor contours representing solitary lesions and an
example with two lesions. For the single tumor cases, different tumor volumes
from 2 to 83 cc were explored, while an example double lesion had a total volume
of 13 cc. Three different source-to-axis distances (SADs), 100, 80 and 65 cm,
were used to create separate 5-field IMRT plans with the same beam angles for all
SADs. For each example, the PTV dose coverage and critical organ doses were
constrained to be the same, except for the normal brain doses that were
determined by the dose conformity. High dose spillage outside the PTV was
quantified by R50 (the ratio between the 50% isodose volume and the PTV), and the
V12 (volume of normal brain receiving 12Gy or higher). RESULTS: R50 decreased
monotonically with shorter SAD for all examples. Compared with 100 cm SAD,
average R50 reductions of 13% and 19% were observed with 80 and 65 cm SAD
respectively. Improved conformity was more notable on smaller lesions and the
multiple lesion case. V12 also decreases significantly with shorter SAD.
CONCLUSIONS: Improvement in dose conformity can be achieved on existing LINACS by
reducing the treatment distance for each IMRT field. Sharper beam penumbra and
smaller projected MLC leaf width contribute to the improvement. Precise delivery
of non- isocentric beams can be challenging on traditional LINACS, but the
problem is much more manageable on machines with precise robotic gantry and couch
capabilities.
PMID- 28517071
TI - SU-E-T-607: Determining Critical Objectives and Importance Factors for Prostate
IMRT Treatment Planning.
AB - PURPOSE: To determine the optimization objectives that are most critical in
prostate IMRT treatment planning, and to demonstrate that clinically acceptable
treatments can be obtained using fewer optimization objectives with intelligently
chosen importance factors. METHODS: We develop a novel optimization method that
uses a historical prostate IMRT treatment as an input to quantify importance
factors for a given set of objectives in the treatment planning problem. An
initial treatment planning formulation with many candidate objectives is
formulated. Then, given a historical treatment, importance factors for the
objectives are determined via inverse optimization. We analyzed the results over
several patients and identified the most critical optimization objectives in
prostate IMRT treatment planning. We then designed a new treatment planning
formulation with only the critical objectives, determined the importance factors
via inverse optimization, and then compared the dose distribution to that of the
original planning problem. The method was applied to a homogeneous cohort of 12
patients from Princess Margaret Hospital. RESULTS: A treatment plan generated
using 18 objectives was replicated using only six objectives and inversely
optimized importance factors. For the bladder and rectum, a combination of the
objective that minimizes the mean dose and the objective that penalizes dose
above 50 Gy was determined to be most critical, while objectives that minimize
the maximum dose were found to be critical for the femoral heads. The bladder and
rectum objectives carried more than 95% of the importance factor over all
objectives. CONCLUSIONS: By identifying critical objectives, our method has the
potential to significantly enhance the computational efficiency of a treatment
planning problem. A simplified treatment planning formulation with importance
factors that are determined via inverse optimization reduces the need for an
iterative, trial-and-error process in treatment planning.
PMID- 28517072
TI - SU-E-T-578: Beam Energy Dependence and Intermediate-Low Dose Bath on Normal
Tissue When Comparing VMAT with Conventional IMRT.
AB - PURPOSE: To evaluate the impact of beam energy and intermediate-low dose bath on
normal tissue when comparing volumetric modulated arc therapy (VMAT) with
conventional IMRT. METHODS: A total of 10 prostate patients were randomly chosen
for this study. The clinical IMRT plans were designed with 5 coplanar 10 MV
photon beams. To investigate impacts of energies and delivery methods, we created
2 additional IMRT plans with 6 and 15 MV photons and 3 VMAT plans with 6, 10, and
15 MV photons in the Pinnacle treatment planning system. All plans were evaluated
in terms of target coverage, clinical endpoints for organs-at-risks (OAR), and
intermediate-low dose distributions to normal tissue, for which endpoints of
V5Gy, V10Gy, V20Gy, V30Gy, V40Gy, and V50Gy were used. For this study, normal
tissue was further divided into near region (5 cm thick concentric shell of
normal tissue surrounding the target) and far region (concentric shell of normal
tissue surrounding the near region and target). Longitudinally, the total normal
tissue in calculation was limited to 10 cm from field edges. RESULTS: No
significant differences were found among 6 types of treatment plans in terms of
target coverage, OAR sparing, plan quality, intermediate-low doses to the near
region, and integral dose to the total normal tissue (p > 0.05). VMAT deposited
less intermediate doses of 30-50 Gy and more low doses of 5-10 Gy to the far
region than IMRT. For example, mean average V40Gy and V10Gy were 51 and 2,967 cc
for VMAT, and 140 and 2,618 cc for IMRT, respectively. CONCLUSIONS: VMAT and IMRT
plans created with different photon energies are comparable for target coverage
and OAR sparing. For prostate treatment, VMAT redistribute normal tissue doses
from intermediate range into low dose range while keeping the similar the
integral dose as IMRT.
PMID- 28517073
TI - SU-E-T-589: There was No Dosimetric Benefit in Sparing Bone Marrow in the
Radiotherapy of Whole Pelvic Lymph Node Applying 6MV X-Ray RapidArc Plans.
AB - PURPOSE: To investigate the dosimetric difference in sparing bone marrow in the
radiotherapy of whole pelvic node comparing 6MV and 15MV X-ray RaidArc plans.
METHODS: Twelve patients who had undergone radical surgery for cervical cancer
and with demonstrated multiple pelvic lymph node metastases were treated with
radiotherapy were selected. All pelvic bone was delineated to define the bone
marrow, and the pelvic bones consisted of the hip bone, the sacrum, the vertebral
body near planning target volume (PTV), and the upper parts of femur. RapidArc
plans applying 6MV and 15MV X-ray with one single whole arc (counter-clockwise
from 179 degrees to 181 degrees ) were generated for each patient, and named
RapidArc-6MV and RapidArc-15MV. The prescription dose was
2.0Gy/fractionx28fractions. The dosimetric differences were compared. RESULTS:
There were no significant differences in conformity index(0.90+/-0.03 Vs 0.89+/
0.04), homogeneity index(1.08+/-0.01 Vs 1.08+/-0.02) and external volume
index(0.08+/-0.04 Vs0. 09+/-0.05) between RapidArc-6MV and RapidArc-15MV(P>0.05).
Neither there were no significant differences in V5 (93.6+/-6.4Vs92.2+/-7.3),
V10(88.6+/-9.3Vs88.3+/-9.2), V20(76.9+/-12.6Vs76.9+/-11.2), V30 (57.9+/-
10.5Vs55.9+/-11.5), V40(35.2+/-10.2Vs34.9+/-10.9) between RapidArc-6MV and
RapidArc-15MV (P>0.05). The monitor untie of RapidArc-6MV (552+/-40Mu) was more
than RapidArc-15MV (455+/-44 Mu) with significant difference (P<0.05).
CONCLUSIONS: Compared to 15MV X-ray RapidArc plans, there was no dosimetric
benefit in sparing bone marrow in the radiotherapy of whole pelvic lymph node
applying 6MV X-ray.
PMID- 28517074
TI - SU-E-T-560: Inter- and Intra-Fraction Variations in Esophageal Dose for Lung
Cancer Patients, and the Impact of Setup Technique and Treatment Modality.
AB - PURPOSE: To understand the dose-response of the esophagus in photon and proton
therapy, it is important to appreciate the variations in delivered dose caused by
inter- and intra-fraction motion. METHODS: Four lung cancer patients were
identified who had experienced grade 3 esophagitis during their treatment, and
for whom their esophagus was close, but not encompassed by, the treatment volume.
Each patient had been treated with proton therapy using 35-37 2Gy fractions, and
had received weekly 4DCT imaging. IMRT plans were also created using the same
treatment planning constraints. In-house image registration software was used to
deform the esophagus contour from the treatment plan to each phase of the 4DCT
for each weekly image set. Daily setup using both bony and soft tissue (GTV)
registration was simulated, and the treatment dose calculated for each CT image.
Changes to the esophagus DVH relative to the treatment plan were quantified in
terms of the relative volume of the esophagus receiving 45, 55, and 65Gy (V45,
V55 and V65). RESULTS: For all combinations of treatment modality (photon,
proton) and setup method (bony, GTV), intra-fraction motion resulted in a range
of V45, V55 and V65 from 3.6 to 5.5%. Inter-fraction motion comparing daily
exhale or inhale phases showed the range of V45, V55 and V65 from 8.5 to 18.6%
(exhale) and 9.8 to 16.3% (inhale). CONCLUSIONS: Inter-fractional motion resulted
in larger variations in dose delivered to the esophagus than intra-fractional
motion. The inter-fraction range for V45, V55 and V65 varied by around 10%
between patients. The treatment modality (photon, proton) and setup technique
(bony, GTV) had minimal impact on the results.
PMID- 28517076
TI - SU-E-T-614: Dose-Reactive Methods in Adaptive Robust Radiation Therapy for Lung
Cancer.
AB - PURPOSE: To perform adaptive radiation therapy treatments for lung cancer using
IMRT; to show that adjusting the target dose after each fraction, in order
to'react' to errors in the dose delivered in prior fractions, can lead to
significant changes in the daily tumor dose over the treatment. METHOD AND
MATERIALS: Before the start of treatment, the beamlet intensities are optimized
to deliver the current target dose distribution for a target set of breathing
patterns at minimal healthy tissue dose. In each fraction, the current beamlet
intensities are delivered, and the patient's breathing pattern is measured. The
breathing pattern set is updated using the breathing pattern, and the target dose
distribution is updated to account for dose errors realized in the previous
fraction. The beamlet intensities are then re-optimized for the updated dose
distribution and uncertainty set, to be used in the next fraction. This process
continues until the end of the treatment. We consider three types of updates to
the target dose distribution: the reactive+/- update, which responds to both
under and overdose; the reactive- update, which responds only to underdose; and
the reactive+ update, which responds only to overdose. RESULTS: On breathing
pattern sequences obtained from real patients, dose-reactive methods result in
final dose performance comparable to non-dose-reactive methods. However, as the
treatment progresses, the reactive+/- update results in growing daily underdose
and overdose, the reactive- update results in growing daily overdose, and the
reactive+ update results in growing daily underdose. In contrast, non-reactive
methods have stable or decreasing tumor underdose and overdose. CONCLUSIONS: By
incorporating dose-reaction, the final tumor dose distribution can be made to
conform closely to the target dose distribution, but at the cost of increasing
tumor underdose and/or overdose. This increasing heterogeneity may have
implications for the biological effectiveness of treatments obtained by dose
reaction.
PMID- 28517075
TI - SU-E-T-600: Utilizing Collimator Rotation to Increase Maximum Treatable Target
Dimensions Using an Elekta Synergy-S with Beam Modulator Multileaf Collimator.
AB - PURPOSE: To determine if a rotated collimator on an Elekta Synergy-S with Beam
Modulator MLC (BMx) allows for dosimetrically acceptable treatment of targets
exceeding the length of the maximum field size (21*16cm). The BMx is a high
resolution MLC with 4mm leaves but is of limited clinical use on patient target
volumes exceeding 20cm in length. Rotation of the collimator utilizes the
Pythagorean geometry to extend treatment length. This potentially increases the
length of the PTV that be conformally treated. METHODS: Rods of 21-23cm length
were contoured in water with the Pinnacle treatment planning system. The width of
the rods varies from 1 -5cm. Four isocentric treatment plans were generated for
each target: four-field conformal, 7-field IMRT, single-arc VMAT, and a modified
double-arc VMAT (MDAV), with the collimator angled at 55 degrees . The MDAV
method consists of two opposing 180 degrees arcs with the collimator turned 55
degrees in opposite directions. A successful plan is defined as 99% of the
target volume being covered by a minimum of 95% of the prescribed dose.
Conformality is determined as a ratio of the volume exposed to prescribed isodose
and target volume. RESULTS: Targets of length 21cm, 22cm, and 23 cm are able to
be treated with widths of 4cm, 5 cm, and 4cm respectively. The MDAV method
achieves these results on all trials. The VMAT method achieves these results for
the 21cm and 23cm long target. The IMRT Method achieves these results for the
21cm long target. With the exception of the 1cm wide targets, the average
conformality is approximately 2.5. CONCLUSIONS: Changing the collimator angle of
the BMx Elekta-S machine allows for a 3cm length increase of targets up to 5cm.
Further work will assess clinical suitability of these findings for treatment of
head and neck tumors and spinal masses.
PMID- 28517077
TI - SU-E-T-591: Volumetric-Modulated Arc Radiotherapy for Carcinomas of the Pituitary
Adenomas: A Treatment Planning Comparison with Fixed Field IMRT.
AB - PURPOSE: A treatment planning study was performed to compare volumetric-modulated
arc radiotherapy against conventional fixed field IMRT on pituitary adenomas
cancer patients. METHODS: CT datasets of 10 patients affected by carcinoma of the
pituitary adenomas were included and four plans were generated for each case:
fixed five-Fields and seven-Fields IMRT, single (RA1)- and double (RA2)-modulated
arcs with the RapidArc technique. The radiation dose was prescribed as 45 Gy in
25 fractions. DVHs were adopted for the statistics of above parameters, as well
as conformal index (CI), homogeneity index (HI), dose-volumetric parameters of
normal tissues, total accelerator output MUs and total treatment time. RESULTS:
Target coverage resulted basically equivalent among four plans. CI and HI were
0.84+/-0.04, 0.84+/-0.03, 0.86+/-0.03, 0.85+/-0.04 and 9.03+/-1.05 8.39+/-1.55,
10.02+/-1.30, 10.59+/-1.30, respectively. The V20Gy (in %) and V40Gy (in %) of
brainstem were 30.48+/-16.84, 10.23+/-7.47, 21.34 +/-12.2, 26.4+/-12.1 and 5.06+/
4.37, 4.27+/-4.49, 3.97+/-4.45, 4.49+/-4.56, repectively. The max dose(Gy)of
Optic nerve-right and Optic nerve-left were 31.87+/-12.04, 33.23+/-12.65, 28.96
+/-13.42, 28.68+/-12.63 and 33.15+/-12.51, 34.15+/-11.51, 30.37 +/-12.41,30.09+/
11.34 .Concerning the healthy brain tissue: V20Gy (in %) was 7.11 +/- 2.1,7.92 +/
2.7, 8.12 +/- 1.8 and 8.0 +/- 2.0, respectively. The number of computed
MU/fraction were 580 +/- 69 (5-IMRT), 598 +/- 112 (7- IMRT),474 +/-43(RA1), and
477 +/- 77 (RA2) . CONCLUSIONS: In our study, rapidarc showed improvement in
organ at risk sparing with uncompromised target coverage .Rapidarc could lead to
the less MU and shortor delivery time compared to IMRT.
PMID- 28517078
TI - SU-E-T-562: Reducing the Arc Span for CSA VMAT Delivery.
AB - PURPOSE: To dosimetrically evaluate advantages and disadvantages of using
multiple, shorter, sub-arcs versus full arc deliveries for treatment of cranio
spinal axis (CSA) irradiation. METHODS: Five (n=5) cranio-spinal axis irradiation
patients were planned using 2 complete arcs, one superior and one inferior; with
gantry rotations from 1 to 359 degrees. Due to supine patient setup, each
original full arc was then replanned split into two sub arcs with gantry
rotations from 1 to 100 and 260 to 359 degrees creating 4 smaller arcs. The PTV
was normalized such that 95% received at least 23.4 Gy in 13 fractions. The PTV
was evaluated based on conformity number and homogeneity index. The normal
structures were evaluated based on maximum and mean doses. Beam on times and
monitor units were compared. RESULTS: Averaged over all patients, conformity
number was calculated to be approximately 0.86 and 0.82 for full arc and sub arc
plans respectively. The homogeneity index was approximately 1.07 and 1.06 for
full arc and sub arc plans. This indicates better target conformity but less
homogeneous dose distribution for full arc plans as compared with sub arc plans.
With the exception of the eyes, each normal structure evaluated had lower maximum
doses with subarc plans. All normal structures, with the exception of the left
kidney, had lower mean doses using sub arc deliveries. Beam on times were shorter
on average for full arcs, but the monitor units were lower on average for sub
arcs. CONCLUSIONS: Overall, CSA patients would benefit from the use of sub arc
treatment deliveries versus full arc deliveries. Nearly all normal structure
doses were lower for sub arcs, while the PTV was still adequately covered and
beam on times and monitor units were similar.
PMID- 28517079
TI - SU-E-T-602: Comparison of Treatment Techniques for Pelvic Node Irradiation:
Intensity-Modulated Photons versus Protons.
AB - PURPOSE: Radiotherapy planning for iliac pelvic nodes can be challenging due to
the close proximity of sensitive healthy tissues such as the bowel and rectum.
Modern treatment techniques like photon intensity-modulated radiotherapy (IMRT)
and intensity-modulated proton therapy (IMPT) offer improved healthy tissue
sparing for similar target coverage. In this study we compare IMRT and IMPT plans
for six post-cystectomy patients. METHODS: A dose of 50.4 Gy was prescribed to
the planning target volume (PTV), which for IMRT is the clinical target volume
(CTV) plus a 5 mm expansion for geometric uncertainties due to CTV and patient
positioning errors, and for proton beams is the CTV plus the lateral 5 mm margin
plus an additional longitudinal margin to allow for the proton range uncertainty.
The optimization objectives are: 98% of the PTV receive at least 95% of the
prescription, target maximum dose = 107% of prescription, rectum V[40Gy] < 30%
and max = 105%, and bowel V[45Gy] < 125 cc and max = 107%. All IMRT and IMPT
plans are made to achieve the target coverage objective. RESULTS: Using IMPT, the
rectum would receive a mean dose of 9.0 Gy with an average (over the six
patients) maximum dose of 38.1 Gy. Using IMRT, the rectum would receive a mean
dose of 13.0 Gy and an average maximum dose of 37.6 Gy. The IMPT plans give a
mean dose of 17.9 Gy and a maximum dose of 53.4 Gy for the bowel, whereas the
IMRT plans give a mean dose of 23.8 Gy and a maximum dose of 53.2 Gy. Both the
rectum and bowel show slightly lower mean doses for IMPT. CONCLUSIONS: Our
results indicate that IMPT plans improve normal tissue sparing as compared to
IMRT plans and provide adequate dose coverage of the target volume.
PMID- 28517080
TI - SU-E-T-573: Quality and Deliverability of Intensity Modulated Neutron
Radiotherapy (IMNRT) Plans.
AB - PURPOSE: Intensity Modulated Neutron Radiotherapy (IMNRT) has been commissioned
for clinical use. The number of allowable segments in IMNRT plans is limited by
MLC speed. Quality and deliverability of static IMNRT treatment plans using the
TG-119 test suite were evaluated to establish guidelines for the number of
segments per plan. METHODS: Treatment plans were created and optimized to
specified constraints for all cases in the TG-119 test suite using the Varian
Eclipse TPS. A 4MV photon beam with similar penetration characteristics as the
fast neutron beam was used as a surrogate for this optimization. Final dose
calculations were performed using an in-house TPS commissioned for neutron dose
calculations. Following optimization, MLC segments were created for three ranges
of total plan complexity - very limited (15-23 segments), limited (24- 31
segments), and unlimited. Calculated DVHs were then compared for compliance with
TG-119 dose constraints. The estimated time of delivery for plans in each range
was calculated based on known delivery parameters. RESULTS: The prostate case
passes all constraints for each complexity level. All other plans fail to meet at
least one constraint for one or more of the complexity levels. For all cases
combined, the very limited, limited, and unlimited complexity levels meet 16, 17,
and 19 of 23 total dose constraints, respectively. The mean estimated delivery
time for the very limited, limited, and unlimited plans is 34 minutes (range: 27
39), 40 minutes (range: 34-45), and 68 minutes (range: 53-81) respectively,
neglecting any delay due to therapists entering the treatment room. CONCLUSION:
IMNRT plan quality is limited by current MLC capabilities. IMNRT plans should be
limited to 25 segments to ensure a reasonable treatment time of 45 minutes. Even
with this small number of segments, we were able to meet most dose constraints
set forth in TG-119.
PMID- 28517082
TI - SU-E-T-595: Comparison of Volumetric Modulated Arc Therapy (VMAT) and Static
Intensity Modulated Radiotherapy (IMRT) for Malignant Pleural Mesothelioma in
Patients with Intact Lungs/Post Pleurectomy.
AB - PURPOSE: This planning study compares VMAT and static gantry, sliding window IMRT
for malignant pleural mesothelioma for post pleurectomy. METHODS: We compared
plans for a left sided (L) and a right sided case (R). Plans used clinically
approved planning target volumes (PTVs) and critical organ contours. IMRT plans
employed 7-8 6 MV photon beam directions over a 215 degrees range centered on
the ipsilateral lung. VMAT plans used 4 partial arcs within the same range and
energy. Prescription dose per fraction was 1.8 Gy; case L went to 50.4 Gy, case R
to 46.8 Gy. Planning objectives were: Lyman model NTCP for both lungs < 25%;
contralateral lung, mean dose < 8 Gy; heart, V30 Gy < 50%, mean < 30 Gy; Each
Kidney, V18 Gy < 33%; liver_not_GTV, mean < 30 Gy, V30 Gy < 50%; stomach not PTV,
mean < 30 Gy; cord maximum < 45 Gy; bowel maximum < 55 Gy, D05 < 45 Gy; PTV D95 =
94%, V95 = 94%, D05 = 115%. Dose calculation was done with the AAA algorithm.
RESULTS: VMAT and IMRT both met the dosimetric constraints. The VMAT MU were 887
(L)_and 896 (R) and for IMRT were 1691 (L) and 2409 (R). IMRT required 14-16
fields (wide-field splitting). The delivery times were 8 minutes (VMAT) and 20
minutes (IMRT). For coverage and plan homogeneity parameters within 1.5% - 2%,
VMAT better spared organs at risk. CONCLUSIONS: Both VMAT and IMRT are feasible
techniques for the treatment of malignant pleural mesothelioma with intact lungs,
with less MU and a shorter delivery time for VMAT. Additional cases must be
planned to test generality of our preliminary results.
PMID- 28517081
TI - SU-E-T-584: Dosimetric Comparison Between Static IMRT and VMAT for a Four- Lesion
Brain Treatment.
AB - PURPOSE: Sparing brain volume is the goal when designing plans for multiple brain
tumors. We compared dose distributions for tumor and normal tissues using VAMT
and static IMRT. METHODS: A patient presented with recurrent meningioma with 4
lesions identified. The greatest dimensions for the tumors were 0.4 to 2.0 cm.
The tumor sizes and locations can be treated with a single plan with 1.8
Gy/fraction, 30 fractions. A 6-field non-coplanar IMRT with the gantry(G) and
couch(C) in IEC scale were used: G0C0, G45C0, G330C0, G240C0, G50C90, and
G120C90. IMRT was performed using iPlan sliding-window. For VMAT, four arcs were
used; two using 350 degree from G175 to G185 and the other two using 175 degree
from G0 to G175. Two arcs were designed with couch=0 and the rest two using
couch=90 degree. VMAT was designed with Eclipse system. Tumors and normal brain
were contoured in the iPlan and then exported to Eclipse to maintain identical
volume. DVH for normal brain was compared for the same tumor coverage from the
two plans. RESULTS: Either static IMRT or VMAT generated an acceptable coverage
for these four tumors. The conformity of tumor coverage was better in VMAT than
that using IMRT; the range of min.-max. doses were: 57.5-63.5 Gy from VMAT vs.
54.1-64.9 Gy from IMRT. For normal brain, DVH did not show a clear difference
between the two plans. For doses 5-15 Gy, VMAT delivered 1- 10% more brain volume
(1040 cc) but 1-2 % less volume in 30-40 Gy than that from static IMRT.
CONCLUSIONS: Either static IMRT or VMAT can adequately be used to treat multiple
lesions with a single isocenteric treatment. VMAT plan demonstrated improved
tumor coverage, spared 1- 2% brain tissue at 30-40 Gy but irradiated up to 10%
more brain in 2-7 Gy. The patient was treated with VMAT.
PMID- 28517083
TI - SU-E-T-566: A Dosimetric Comparison of Partial Breast Irradiation Technique
Depending on the Tumor Locations in Patient's Breast.
AB - PURPOSE: The present study was designed to suggest the optimal treatment
modalities among 3D-conformal radiation therapy, electron beam therapy and
helical-tomotherapy depending on classified tumor locations in patient's breast
using Partial Breast Irradiation (PBI) technique. METHODS: The CT dataset of six
patients who had received lumpectomy treatments was used to treatment plans of 3D
conformal radiation therapy, electron beam therapy and helical-tomotherapy. The
tumor locations were classified into eight sections according to the quadrants of
the breast and to the superficial or deep positions. To evaluate the dosimetric
results from the suggested treatment modalities and tumor locations, conformation
number, radical dose-homogeneity and delivered doses to normal tissue were
calculated. Kruskall-Wallis, Mann-Whitney U and Bonferroni method was used as
statistical analysis. RESULTS: Helical-tomotherapy is not recommendable method in
PBI technique because the dosimetric results from radical dose- homogeneity and
the delivered dose to organ at risk showed worse results at all tumor locations
compared to other modalities. For helical-tomotherapy, the volume of heart
received more than 2.5 Gy was maximized more than 90% of total heart volume at
all tumor locations. Electron beam therapy showed good sparing effect to normal
tissues and acceptable target coverage in Lower Inner Quadrant-Superficial (LIQ
S) and Lower Inner Quadrant- Deep (LIQ-D) cases. CONCLUSIONS: Electron beam
therapy could be recommendable method to treat tumor at LIQ-S, LIQ-D locations
rather than 3D-conformal radiation therapy, helical-tomotherapy at PBI technique
because electron beam therapy is considered to provide the acceptable target
coverage and the greatly lower dose to surrounding tissue.
PMID- 28517084
TI - SU-E-T-606: Optimal Emission Angle Selection in Rotating Shield Brachytherapy.
AB - PURPOSE: In this work a general method is presented that enables clinicians to
rapidly select Rotating shield brachytherapy (RSBT) emission angles based on the
patient-specific tradeoff between delivery time and tumor dose conformity.
Cervical cancer cases are used as examples. METHODS: Anchor plans with high dose
conformity but infeasible delivery times are generated with a fine emission
angle, with simulated annealing. The RSBT emission angle selector determines the
optimal emission angle for each case by efficiently solving a globally-optimal
quadratic programming problem that closely reproduces the angular distribution of
beam intensities from the anchor plan. Pareto plots of the dosimetric plan
quality metrics, such as D90 versus the delivery time, are generated for
clinicians. In this work two cervical cancer cases were considered for
verification. The RSBT system was assumed to be a Xoft AxxentTM electronic
BT(eBT) source with a 0.2mm tungsten shield. The intent for each treatment plans
was to maximize tumor D90 while respective the GEC-ESTRO recommended constraints
on the D2cc values to OARs. RESULTS: Generating anchor plans with simulated
annealing takes 10-20min while emission angle selection can finish within
seconds. The shield sequencing algorithm also ensures the balance between D90 and
delivery time. One case shows that the D90 can achieve 98.3Gy10 with emission
angle 202.5 degree with 8.64min delivery, while the conventional intracavitary
plan has D90 65Gy10 with 2.86min delivery. Another case shows RSBT with emission
angle 67.5 degree can produce D90 108.7Gy10 with 44min, and the conventional plan
uses 2.2min for D90 48.9Gy10. CONCLUSIONS: The RSBT emission angle selection
algorithm enables the users to rapidly determine the best emission angle for a
given cervical cancer case by selecting the most appropriate D90 and delivery
time. RSBT may be a less invasive alternative to intracavitary and supplementary
interstitial BT for the treatment of cervical cancer tumors, supported in part by
NSF grants CCF-0830402 and CCF-0844765, the NIH grant K25-CA123112.
PMID- 28517085
TI - SU-E-T-577: Dosimetric Comparison of Volumetric Modulated Arc Therapy (VMAT),
Step and Shoot and Sliding Window IMRT for Prostate Cancer.
AB - PURPOSE: This study aims to evaluate treatment plans generated by Step- and-Shoot
(SS), Sliding Window (SW) and Volumetric Modulated Arc Therapy (VMAT) in order to
assess the differences in dose volume histograms of planning target volume (PTV)
and organs at risk (OAR), conformity indices, radiobiological evaluations, and
plan quality for prostate cancer cases. METHODS: Six prostate cancer patients
treated in our center were selected for this retrospective study. Treatment plans
were generated with Eclipse version 8.9 using 10 MV photon beams. For VMAT,
Varian Rapid Arc with 1 or 2 arcs, and for SS and SW IMRT, 7-9 fields were used.
Each plan had three PTVs with prescription doses of 81, 59.4, and 45 Gy to
prostate, to prostate and lymph nodes, and to pelvis, respectively. Doses to PTV
and OAR and the conformal indices (COIN) were compared among three techniques.
The equivalent uniform dose (EUD), tumor control probability (TCP) and normal
tissue complication probability (NTCP) was also calculated and compared. RESULTS:
The mean doses to the PTV prostate on average were 83 Gy and the percent
differences of mean dose among all techniques were below 0.28. For bladder and
rectum, the percent differences of mean dose among all techniques were below 2.2.
The COIN did not favour any particular delivery method over the other. The TCP
was higher with SS and SW for four patients and higher with VMAT for two
patients. The NTCP for the rectum was the lowest with VMAT in all patients except
one. CONCLUSIONS: Preliminary data shows similar target coverage in general. We
will extend our study to include 15 patients to compare different approaches with
statistics. We will attempt to define characteristics predictive of the superior
delivery technique.
PMID- 28517086
TI - SU-E-T-588: A Treatment Planning Comparison of Dual-Arc VMAT Vs. Helical
Tomotherapy for Post-Mastectomy Radiotherapy.
AB - PURPOSE: To investigate the feasibility of volumetric modulated arc therapy
(VMAT) for post-mastectomy radiotherapy (PMRT) and to compare dual- arc VMAT
treatment plans to helical tomotherapy (HT) plans on the basis of dosimetric
quality, radiobiological calculations and delivery efficiency. METHODS: Dual-arc
VMAT and HT treatment plans were created for fifteen patients previously treated
at our clinic. Planning target volumes (PTV) included the chest wall (CW) and
regional lymph nodes. The following metrics were used to compare treatment plans
for each patient: dose homogeneity index (DHI) and conformity index (CI);
coverage of the PTV; dose to organs at risk (OAR); tumor control probability
(TCP), normal tissue complication probability (NTCP) and secondary cancer
complication probability (SCCP); and treatment delivery time. Differences between
treatment plans were tested for significance using the paired Student's t-test.
RESULTS: Both modalities produced clinically acceptable PMRT plans. VMAT plans
showed better CI (p < 0.01), and better OAR sparing at low doses than HT plans.
For example, VMAT plans showed a 26% (p < 0.01) and 9% (p < 0.01) decrease in
V5Gy in the lungs and heart respectively. On the other hand, HT plans showed
better DHI (p < 0.01) and PTV coverage (p < 0.01). HT plans also showed slightly
better OAR sparing at higher doses, including 8% (p < 0.01) and 9% (p < 0.01)
lower maximum doses to the lungs and heart, respectively. Both modalities
achieved nearly 100% tumor control and approximately 1% NTCP in the lungs and
heart, with VMAT showing lower SCCP (p < 0.01). VMAT plans also required 66.2%
less time to deliver. CONCLUSIONS: Both VMAT and HT are suitable treatment
options for PMRT. Our study showed that VMAT"'in addition to being significantly
faster'"achieved better CI and low dose OAR sparing while HT achieved better DHI.
This work was supported in part by a research support from Elekta, Ltd. However,
Elekta, Ltd., did not participate in the study design; in the collection,
analysis, and interpretation of data; in the writing of the manuscript; or in the
decision to submit.
PMID- 28517087
TI - SU-E-T-559: Evaluation of Flatening Filter Free (FFF) Beams in Radiotherapy of
Head and Neck Cancer.
AB - PURPOSE: To investigate th applicability of the flattening filter free (FFF) to
fractionated radiotherapy of head and neck cancer. METHODS: Twelve patients
previously treated with IMRT were selected. A SIB protocol was chosen so that
66/54 Gy were prescribed to the gross tumors/elective nodal volumes in 30
fractions. Photon beams of 6X(6X-FFF) were used for both IMRT (@ 9 gantry angles)
and VMAT (single and dual full arcs). Consistent optimization and acceptance
criteria were used for all plans, with prescription dose to cover 90% of PTV66
and hot spots limited to 110% and within PTV66. Both plan quality and deliver
ability were compared. RESULTS: All plans met clinical objectives. The IMRT plan
quality is similar or slightly better than VMAT, except that PTV66 conformity
index is significantly better in 2-arc VMAT (1.18) than IMRT (1.32). The total
MUs for IMRT are 1680/2090 for 6X/6X-FFF, a 24% increase. However, the total beam
on time (BOT) under treatment automation is 430/400 seconds for 6X(@300
MU/min)/6X-FFF (@400 MU/min), a 6% decrease. Increasing dose rate to the maximum
(600/1400 for 6X and 6X-FFF) can reduce BOT by up to 50%, but at a cost of
increased MU (up to 40%) and degraded plan quality. Significant reduction in MU
and BOT are realized in VMAT, with ~600 MU for both 6X and 6X-FFF and either
single or dual-arcs. The BOT for VMAT is governed by the gantry speed and
approximately 1 min for single arc and 2 min for dual arcs. CONCLUSIONS: Plan
quality is similar between IMRT and 2-arc VMAT for both 6X and 6X-FFF. Total MU
for IMRT and delivery time is significantly higher for IMRT than VMAT, but not
much different between flat and non-flat beams. For standard fractionated
radiotherapy of HN cancer, there is no advantage for the non-flat beam. The
recommended choice is 2-arc VMAT.
PMID- 28517088
TI - SU-E-T-599: Pelvic Volumetric Modulated Arc Therapy with Hypofractionated
Concomitant Integrated Prostate Boost: An Isoeffective Dose Comparison.
AB - PURPOSE: Pelvic irradiation is controversial in prostate cancer and has been
associated with significant late toxicity, but may be beneficial in patients with
high risk disease. To evaluate dose reduction to organs at risk (OAR), we
compared volumetric intensity modulated arc therapy with hypofractionated
concomitant integrated prostate boost (VMAT) to sequential 3-D conformal 4 field
pelvis plan and prostate IMRT boost (Sequential IMRT). METHODS: The planning CT's
of 20 consecutive high risk prostate cancer patients were utilized for this
study. Dose planning using triple A algorithm (Varian Eclipse). CTV included
prostate and proximal seminal vesicles. These were expanded by 6 mm for the PTV1
. Pelvic LN were delineated and expanded by 3 mm for the PTV2. Volume based
equivalent dose at 2Gy/fx (EQD2) doses were calculated using alpha/beta ratios of
1.5 Gy for the prostate and 3 Gy for normal tissues. VMAT prescription was 73.6
Gy (EQD2-80 Gy) to PTV1 and 54.4 Gy to PTV2 (EQD2-50 Gy) in 32 fractions of 2.3
Gy and 1.7 Gy, respectively. Sequential prescription was 46 Gy to the pelvis and
34 Gy for IMRT boost to a total of 80 Gy in 40 fractions of 2 Gy each. RESULTS: A
significant reduction in mean dose was observed for rectum, bladder, bowel, femur
head, and penile bulb for VMAT vs. Sequential IMRT (p<0.001) (table 1). Rectal
V75 and V70 was 6.2% and 11.2% for VMAT and 13.6% and 19% for Sequential IMRT
(p<0.001). Bowel V50 was 0.35 cm3 vs. 24.1 cm3 (p<0.001), respectively. The 98%
isodose conformity index for the PTV was 1.44 for VMAT vs. 1.69 for Sequential
IMRT (p<0.001). CONCLUSIONS: VMAT with concomitant boost significantly reduced
dose to OAR compared to Sequential IMRT, potentially leading to less late
toxicity, while providing excellent target coverage and conformity. Furthermore,
reduction of treatment planning time and both individual fraction and overall
treatment delivery time inherent in this approach, offer significant advantages
for both providers and patients.
PMID- 28517089
TI - SU-E-T-570: Improvement to the Histogram Analysis in Radiation Therapy (HART): An
Open Source Software System for the Multi-Dimensional Dose- Volume Histogram
Analysis in Digital Image Communication in Medicine - Radiation Therapy (DICOM
RT) Treatment Plans.
AB - PURPOSE: Histogram Analysis in Radiation Therapy (HART) is an efficient and
accurate dose-volume histogram (DVH) computational tool in radiotherapy research.
Several applications of the program have been presented previously (J Appl Clin
Med Phys 11(1): 3013, 2010; Med Phys 38(6), p.3678, 2011) for the Radiation
Therapy Oncology Group (RTOG) users. The program has been further developed to
incorporate various types of DVH analysis features to support the research using
DICOM-RT plans. The main objective of this work was to present the improvement
and compatibility of the program for the DICOM-RT plans. METHODS AND MATERIALS:
MATLAB based codes were primarily designed to read and write a simpler HART
format from the standard DICOM-RT data objects exported from the Xio treatment
planning system (CMS Inc., St. Louis, MO). This format employed an optimal
polynomial fitting technique to interpolate the co-ordinates of the contours in
the regions-of-interest. The format was efficient for the (a) precise extraction
of the cumulative DVH (cDVH) and spatial DVH (sDVH; x-,y-, and z-DVHs
respectively) data- statistics, (b) universal-plan indices evaluation, (c)
biological modeling based outcome analyses (BMOA), (d) radiobiological dose
response modeling, and (e) physical parameterization modules. The fundamental DVH
statistics were validated using the DVH statistics extracted from the
Computational Environment for Radiotherapy Research program. RESULTS: HART offers
various types of DVH computational functionalities, several plan evaluation and
radiobiological outcome analysis modules in a user- friendly software package for
the RTOG and DICOM-RT planners. The cDVH and BMOA modules were found to be the
most applicable features for the global researchers. CONCLUSIONS: HART is a novel
and universal multi-dimensional DVH analysis tool for the radiation therapy
research. We further expect to develop HART for the space-time DVH analysis and
proton therapy applications. The software is available online
(http://www2.uic.edu/~apyaku1) for the radiotherapy research. This work was
partially supported by NIH-NIDCD grant.
PMID- 28517090
TI - SU-E-T-610: Impact of Variable Beam Spot Size on Treatment Time in Particle
Therapy.
AB - PURPOSE: The dosimetric advantage of particle therapy comes with a much higher
infrastructure investment and operation costs. Increasing patient throughput is a
key factor to manage operation costs. We investigate the impact of variable beam
spot sizes on treatment time and discuss the tradeoffs involved. METHODS: The
following realistic assumptions were used. (1) The beam traveling speed is
independent of the beam spot size. (2) The beam spot is a 2D Gaussian. Changing
the beam spot size implies varying the standard deviation. (3) The maximum beam
intensity is a constant independent of the beam spot size. Increasing the beam
spot reduces the fluence. (4) Varying the beam spot size incurs in a reset time
penalty.A 2D tumor was used in the study. Dose calculations were based on pencil
beam kernels from GEANT4.The total treatment time is divided into the beam travel
time, the beam-on time, andthe time for changing the spot size. RESULTS: We found
that: (1) Changing the beam spot size has no impact on the beam-on time, because
the maximum beam intensity is independentof the beam spot and increasing the beam
spot only reduces the fluence. (2) Larger beam spot size shortens the total
travel time inversely proportional to the radius of the beam spot. (3) Plans with
different beam spot sizes have similar dosimetric qualities. (4) If higher beam
intensity could be used for larger beam spot size, savings in beam-on time would
be inversely proportional to the intensity available. CONCLUSIONS: We have
studied the interplay among beam intensity, travel time, and beam size reset time
for a scanning beam with variable beam spot size. Our initial studies show
necessary conditions for and limitations on savings in total treatment times.
Further studies are being carried out to find additional time saving sources.
Supported in part by NSF CBET-0853157.
PMID- 28517091
TI - SU-E-T-613: Improving Dose-Shaping and OAR-Sparing Using Robust Statistical
Methods.
AB - PURPOSE: To achieve a better balance between tumor coverage and organ-at-risk
(OAR) sparing by applying robust statistical methods to IMRT inverse
optimization. METHODS: We propose a novel approach to shape dose dropoff from the
PTV by minimizing the L1 norm of the difference between the obtained and aimed
dose value and the total variation of the dose distribution on the PTV and OAR
regions. Minimizing the L1 norm results in operand values that are mostly small
but potentially large on a sparse set. Applying this structure to both dose
discrepancy and dose gradient, our method achieves: 1) sparsely-distributed, high
dose gradients; 2) structure dose-homogeneity; and 3) connectivity in the
distribution of high-gradient voxels on the PTV's surface. Dose-volume histograms
(DVHs) and visual observations of dose maps were compared among two plans
optimized for the same dynamic IMRT prostate case: 1) the clinical plan (plan_c);
and 2) a plan optimized using the TV energy, L-1 norm, and an over-dose quadratic
(plan_r). Importance factors for the objective function of planr were chosen
empirically. The beam geometry was obtained from the clinical plan, and the
solution was optimized with linear programming. RESULTS: Plan_r improved dose
conformity, increased overall bladder-sparing, and globally increased rectum
sparing relative to plan_c. CONCLUSIONS: These results suggest that robust
formulations may be used to improve dose-shaping and OAR-sparing. The numerical
stability and implementation simplicity of our method permits fast translation to
the clinic.
PMID- 28517092
TI - SU-E-T-561: A Comparative Study of Single Verses Two Field Daily Fraction for
Treatment of Prostate Cancer Using IMPT, Double-Scattered, and SUFD Delivery
Technique.
AB - PURPOSE: We conducted an investigation to evaluate the robustness of different
proton therapy delivery technique for treatment of prostate cancer. Three
commonly used delivery techniques; intensity modulated, double-scattered, and
single field uniform dose delivery was investigated for one field verses two
field daily fraction. METHOD: Computer tomography (CT) for a patient was deformed
based on acquired daily MVCTs obtained during the course of treatment by a
Tomotherapy unit. The deformed CTs were used for proton planning
retrorespectively using intensity modulated (IMPT), double-scattered (DSPT), and
single field uniform dose (SFUD) delivery technique. The plans were evaluated for
single-field versus two-field per fraction for each technique. The plans
robustness was evaluated for each technique by comparing the maximum dose to
rectum, bladder, prostate and CTV as well as the minimum dose to prostate and
CTV. In addition, 95% coverage to prostate and CTV compared for each plan.
RESULTS: The average and STD for deformed prostate volume was 22.4 +/-0.5 (1s)
for the course of treatment. On average the maximum dose delivered to rectum and
bladder with single-field verses two-field IMPT were higher by 2.5%. With same
respect, the single-field verses two-field for DSPT were 0.5% higher for rectum
but the same for bladder. Single-field SFUD delivered 1% higher dose to both
rectum and bladder compare to two-field delivery. Table 1 summarizes the results.
CONCLUSION: Single-field IMPT delivered higher dose to rectum, bladder, prostate,
and CTV than any other technique. But two-file IMPT delivered most homogenous and
consistent dose to prostate and CTV with much lower dose to rectum and bladder
compare to DSPT and SFUD. With same respect two-field SFUD delivery produced
better dose coverage to prostate and CTV compare to DSPT. The two-field IMPT with
conjunction of daily cone beam CT can be considered a better dose delivery
technique.
PMID- 28517093
TI - SU-E-T-601: Dosimetric Evaluation of the Parameter Variation with Varying
Calculation Grid Size in the IMRT Cases.
AB - PURPOSE: The aim of this study is to compare the plan results that are obtained
by using different calculation grid sizes ranging from 0.15 to 0.50 cm, and the
same dose calculation algorithm (Superposition), in Intensity Modulated
Radiotherapy (IMRT) for different treatment sites. Results are then used to study
the suitability of dose grid size with respect to site. METHODS: For each of the
calculation grid sizes, three different sites; namely, Lung, Prostate, and Head
and Neck were analyzed. Treatment plans were created using 6MV photon beam
quality and IMRT technique on the CMS XiO (Computerized Medical System, St.Louis,
MO) treatment planning system. Dose volume histograms were generated for each of
the cases and statistical analysis performed included mean relative difference
and Homogeneity Index for target structures. Comparison was done first by using
0.30 cm calculation grid as a golden standard and keeping the same number of
monitor units (MUs) per beam for each grid size, then the second part involved
renormalizing plans to have the same target coverage (100% of the prescription
dose covering at least 95% of the target volume) for each grid size used. Future
study plans include treatment plans delivery on Varian 21 EX linear accelerator
with Millennium (120) MLC and their verification with the Sun Nuclear Mapcheck 2D
array. To increase the diode array resolution, 2D array will be shifted in 1 mm
increments in x and y direction. Measured fields will be merged using Sun Nuclear
Files Combined function and compared with intensity maps exported from the CMS
XiO treatment planning system calculated with minimum segment size of 1 cm.
RESULTS: The maximum percentage of variation recorded between calculation grid
sizes used was in the case of the Head and Neck treatments. For the lung and
prostate cases there was little variation in the results based on the calculation
grid size chosen, specifically between 0.30, 0.20 and 0.15 cm. However head and
neck and prostate cases with nodal involvement showed significant variation in
the dosimetric results based on the grid size chosen. Overall results vary from
case to case and also depend on the plan complexity. For larger treatment areas
calculating with the grid size smaller than 0.30 cm may be impossible as time
needed for calculation rises exponentially with the field size involved.
CONCLUSIONS: IMRT places a higher requirement on dose grid resolution than
conventional radiation therapy. While 0.30-0.40 cm grid was assumed adequate for
conformal treatment planning, smaller dose grid is required at least in the areas
of high dose. In the cases where steep dose gradients exist smaller grid size
should be used while calculating and evaluating treatment plans, as the choice of
the calculation grid size may in certain cases even influence clinical results.
PMID- 28517094
TI - SU-E-T-572: A Plan Quality Metric for Evaluating Knowledge-Based Treatment Plans.
AB - PURPOSE: In prostate IMRT treatment planning, the variation in patient anatomy
makes it difficult to estimate a priori the potentially achievable extent of dose
reduction possible to the rectum and bladder. We developed a mutual information
based framework to estimate the achievable plan quality for a new patient, prior
to any treatment planning or optimization. METHODS: The knowledge-base consists
of 250 retrospective prostate IMRT plans. Using these prior plans, twenty query
cases were each matched with five cases from the database. We propose a simple
DVH plan quality metric (PQ) based on the weighted-sum of the areas under the
curve (AUC) of the PTV, rectum and bladder. We evaluate the plan quality of
knowledge-based generated plans, and established a correlation between the plan
quality and case similarity. RESULTS: The introduced plan quality metric
correlates well (r2 = 0.8) with the mutual similarity between cases. A matched
case with high anatomical similarity can be used to produce a new high quality
plan. Not surprisingly, a poorly matched case with low degree of anatomical
similarity tends to produce a low quality plan, since the adapted fluences from a
dissimilar case cannot be modified sufficiently to yield acceptable PTV coverage.
CONCLUSIONS: The plan quality metric is well-correlated to the degree of
anatomical similarity between a new query case and matched cases. Further work
will investigate how to apply this metric to further stratify and select cases
for knowledge-based planning.
PMID- 28517095
TI - SU-E-T-617: Towards Fully Automated Multi-Criterial Plan Generation: A
Prospective Clinical Study.
AB - PURPOSE: To prospectively compare plans generated with iCycle, an in-house
developed algorithm for fully automated multi-criterial IMRT beam profile and
beam orientation optimization (Breedveld, Med. Phys. 2012), and plans manually
generated by dosimetrists with the clinical treatment planning system. METHODS:
For 20 randomly selected head-and-neck cancer patients with various tumour
locations (of whom 13 received sequential boost treatments) we offered the
treating physician the choice between an automatically generated iCycle plan and
a manually optimized plan following standard clinical procedures. While iCycle
used a fixed'wish-list' with hard constraints and prioritised objectives, the
dosimetrists manually selected the beam configuration and fine-tuned the
constraints and objectives for each IMRT plan. Dosimetrists and treating
physicians were not informed in advance whether a competing iCycle plan was made
or not. The two plans were simultaneously presented to the physician who then
selected the plan to be used for treatment. For the patient group, we quantified
differences in PTV coverage and sparing of critical tissues. RESULTS: In 32/33
plan comparisons the physician selected the iCycle plan for treatment. This
highly consistent preference for automatically generated plans was mainly caused
by improved sparing for the large majority of critical structures. With iCycle,
the NTCPs for parotid and submandibular glands were reduced by 2.4% +/- 4.9%
(maximum: 18.5%, p=0.001) and 6.5% +/- 8.3% (maximum: 27%, p=0.005),
respectively. The reduction in mean oral cavity dose was 2.8 Gy +/- 2.8 Gy
(maximum: 8.1 Gy, p=0.005). For swallowing muscles, esophagus and larynx, the
mean dose reduction was 3.3 Gy +/- 1.1Gy (maximum: 9.2 Gy, p<0.001). Moreover,
for 15 patients, the target coverage was improved as well. CONCLUSIONS: In 97% of
cases, the automatically generated plan was selected for treatment because of
superior quality. Apart from improved plan quality, automatic plan generation is
economically attractive because of reduced workload.
PMID- 28517096
TI - SU-E-T-583: Feasibility of Constraining Dose to the Nausea Center (area Postrema
and Dorsal Vagal Complex) in IMRT Treatment Planning of the Head and Neck.
AB - PURPOSE: Nausea and vomiting have been known to occur in patients undergoing
external beam radiation treatments for head&neck cancers. We sought to determine
the feasibility of limiting the dose delivered to the nausea center, area
postrema (AP) and dorsal vagal complex (DVC), for these patients without
compromising target coverage and critical organ doses. METHODS: In a
retrospective study 23 oropharyngeal cancer patients were identified as being
treated with definitive or adjuvant radiotherapy at Memorial Sloan Kettering
Cancer Center. Patients were treated solely with external beam radiation using
intensity modulated radiation therapy (IMRT). The nausea center was carefully
contoured in the treatment CT with the assistance of a board certified
neuroradiologist. The doses delivered to the nausea center were calculated for
each plan delivered. Cases were replanned offline to determine the lowest
achievable nausea center dose that does not compromise the overall PTV coverage
or critical structures doses, these being brainstem, spinal cord, cochleas, and
temporal lobes. RESULTS: Patients reporting higher nausea grade had median AP and
DVC doses of 38.7Gy and 40.4Gy, respectively. Patients reporting higher vomiting
grade had median AP and DVC doses of 39.5Gy and 44.7Gy, respectively. Replanning
resulted in reduced dose to AP by an average of 18% and to the DVC by an average
of 16% while maintaining adequate target coverage and doses to the critical
organs the same or decreased by 1-4% . We aim to achieve a max dose of 36Gy to AP
and 38Gy to DVC for these cases. CONCLUSIONS: It is feasible to limit the doses
to the nausea center without compromising target coverage or critical organ
limits for oropharyngeal cancer patients undergoing IMRT treatment. Clinical
results indicating an association between radiation dose to the nausea center and
development of nausea and/or vomiting can potentially be addressed by
implementing this technique.
PMID- 28517097
TI - SU-E-T-594: Dosimetric Evaluation of Different Treatment Techniques for Prostate
Cancer.
AB - PURPOSE: To evaluate the Volumetric Modulated Arc Therapy (VMAT, RapidArc) and
IMRT plan quality for prostate deliveries conducted by two different treatment
planning systems: Oncentra Masterplan (Nucletron inc.) and Eclipse (Varian inc.).
METHODS: We investigated ten prostate treatment delivery plans. For a given case
studied we created a RapidArc plan (Eclipse), a VMAT and an IMRT plan (Oncentra)
by using both treatment planning systems. The rotational therapy plans consisted
of 2 to 3 arcs and the IMRT fields consisted of 7 to 9 fields. The prescription
dose was 200 cGy X 40 fx using a Varian Trilogy with 10 MV beams. The treatment
parameters were used to evaluate the plan quality: the minimal, mean and maximal
doses to the target (PTV) and the volumes received 65Gy and 40 Gy, respectively,
for the rectum and bladder, V65 and V40. In addition, we calculated the
conformity index (CI) and the heterogeneity index (HI) for each delivery type.
RESULTS: No significant difference was found between RapidArc, VMAT and IMRT,
regarding the minimal and average PTV dose value. The rectum and bladder
constraints showed no significant variation as well. The PTV hot spot was
significantly higher for the VMAT plan compared to the RapidArc plan (p=0.007).
The target CI for VMAT (0.55+/-0.05) and IMRT (0.71+/-0.08) was found to be
smaller than the RapidArc (0.82+/-0.04) and the difference is statistically
significant (p=0). The HI, value was found to have no significant difference
between RapidArc, VMAT and IMRT plan deliveries. CONCLUSIONS: Two TPS are capable
of producing high-quality treatment plans for prostate cancer. The quality is
associated with the degree of intensity modulation and the number of incident
angles. Overall, the RapidArc plans with 2-3 arcs showed better dosimetric
qualities than the VMAT and IMRT plans.
PMID- 28517098
TI - SU-E-T-565: Effectiveness of Robust Optimization in Head and Neck IMPT Dose
Distributions.
AB - PURPOSE: The effectiveness of IMPT may be significantly diminished by range and
patient setup uncertainties. The purpose of this presentation is to evaluate the
ability of robust optimization methods to desensitize H&N IMPT plans to
uncertainties and their impact on plan optimality. METHODS: We use a robust
optimization method, in which the objective function value for a given iteration
is computed using the 'worst case' dose distribution. The conventionally
optimized PTV-based IMPT plans and robustly optimized plans were generated for 14
head and neck cancer cases. The dose standard deviation was calculated for every
voxel and used to compute 'standard-deviation volume histograms' (SVHs). The area
under SVH curves was used to quantify the plan robustness. In addition, D1cc
doses for spinal cord and brainstem, mean doses Dmean for oral cavity and
parotids, and D1% doses for other organs were used to assess plan optimality. D5%
and D95% doses are used to assess target dose coverage and homogeneity. The plan
optimality and robustness are then compared statistically by the pair t-tests
using SPSS 19.0 software. RESULTS: Compared with PTV-based optimization, robust
optimization provides significantly more robust dose distribution for both
targets and organs without sacrificing, and possibly even improving, the sparing
of normal tissues. In addition, our robust optimization method also leads to more
homogeneous dose distribution in targets with better prescription dose coverage.
Improvements are statistically significant with p-value smaller than 0.05 for
almost all end points compared. CONCLUSION: Robust optimization results in
patient-specific, optimizer-determined, and effectively reduced margins compared
to a predefined and fixed margin used in the PTV approach. The optimizer can find
a desired beamlet weight solution from the degenerate solution space so that the
dose distribution follows the changes in anatomical geometry and is minimally
perturbed by uncertainties. Our results demonstrate the importance of robust
optimization. This research is supported by National Cancer Institute (NCI) grant
P01CA021239, the University Cancer Foundation via the Institutional Research
Grant program at the University of Texas MD Anderson Cancer Center, and MD
Andersona?TMs cancer center support grant CA0 16672.
PMID- 28517099
TI - SU-E-T-605: RapidArc Combined with DIBH Technique for Thoracic Esophageal
Carcinoma: The Potential Value of Target Immobilization and Reduced Lung Density
in Dose Escalation.
AB - PURPOSE: To compare the dosimetric benefits of Rapidarc (RA) combined with deep
inspiration breath-hold (DIBH) with those of other standard techniques, including
free breathing (FB) during fixed-field intensity modulated radiation therapy
(IMRT) and dual arc RA, in the treatment of patients with thoracic esophageal
carcinoma (EC). METHODS: Ten patients with EC underwent computed tomography (CT)
scans under 2 respiration conditions: free-breathing (FB) and DIBH. These scans
were used to generate 3-dimensional conformal treatment plans. For breath-hold
scans, the patients were brought to reproducible respiration levels using active
breathing control (ABC) maneuvers. Planning target volumes (PTVs) for FB plans
included a 0.5 cm margin for setup plus a 1 cm margin equal to the extent of
tumor motion for respiration. PTVs for DIBH plans included a 0.5 cm margin for
setup error and a 0.5 cm margin for residual uncertainty in tumor position. Using
a dose level of 60 Gy to the PTV, three treatment plans were generated: IMRT-FB,
RA-FB and RA-ABC, and the target and normal tissue volumes were compared, as were
the dosimetry parameters. RESULTS: On average, the DIBH technique resulted in
increased lung volumes compared with FB techniques. There was no significant
differences in gross tumor volume between the two breathing states (p > 0.05);
but PTV and heart volume were larger for FB than for DIBH (p < 0.05). The overall
CI and HI for the RA-ABC plan was slightly inferior to those of the IMRT- FB and
RA-FB plans (p < 0.05 each). With DIBH, the heart was partly out of the beam
portals and the average mean heart dose was reduced. CONCLUSIONS: Compared with
conventional FB, RA combined with DIBH significantly reduced cardiac and
pulmonary doses without compromising the target coverage and may reduce treatment
toxicity, enabling dose escalation in future prospective studies of patients with
EC.
PMID- 28517100
TI - SU-E-T-576: Investigation of Combining Modulated Electron Beams with Intensity
Modulated Photons for Radiation Therapy of Breast Cases.
AB - PURPOSE: Modulated electron radiation therapy (MERT) can offer significant
advantages for breast treatments over conventional radiotherapy in terms of
sparing distal critical structures. While intensity modulated radiation therapy
(IMRT) has the advantage of achieving better dose homogeneity inside the target
combining both MERT and IMRT will be the ideal scenario. The Aim of the present
study is to investigate the possibility of further improving breast radiation
therapy using combined MERT/IMRT treatment technique. METHODS: Accurate modeling
of a prototype motorized electron multileaf collimator was verified in a separate
study. In this work treatment planning was performed by an in house Monte Carlo
based inverse planning system. Dose deposition coefficients were calculated using
MCPLAN and utilizing real patients CTs. Optimization is then conducted based on
an equivalent uniform dose objective function. MERT and IMRT plans were created
for different patients. RESULTS: The clinical beneficial outcome for MERT either
alone or combined with IMRT was investigated based on isodose distributions and
dose volume histograms. It is shown that MERT can give similar dose distributions
as IMRT in some cases. For some cases, MERT could be advantageous whenever more
skin dose was required. In some cases MERT can be identified as the best option.
It was found that MERT compared to IMRT could introduce hot spots inside the
target. However this was resolved in combined MERT/IMRT treatment. Dose
uniformity can be restored with a reduction in the maximum lung and heart
received dose. CONCLUSION: MERT can improve treatment plan quality for many
breast patients. In some cases better results can be obtained with a combined
MERT/IMRT treatment, where a homogeneous dose in the target can be achieved with
an improvement in the DVH of critical structures. This work has been supported by
a UICC American Cancer Society Beginning Investigators Fellowship funded by the
American Cancer Society.
PMID- 28517102
TI - SU-E-T-598: Clinical Experience of Configuration, Commission and Implementation
for SmartArc with MOSAIQ R&V System.
AB - PURPOSE: Clinical experience for configuration, commission and implementation of
SmartArc with MOSAIQ R&V system. METHODS: SmartArc is Pinnacle's solution for
VMAT. On July 2011 we updated to Pinnacle 9.0 and purchased SmartArc. A
standalone Eclipse workstation has been used 3 years for VMAT planning. Our
clinical setting: Mosaiq 2.2; Varian Trilogy driven by 4DiTC and Varian 21ex
driven by sequencer. Some key physics parameters have been studied: machine dose
rate; MLC leaf speed; Leaf motion per gantry rotation. Tabletop was created by
user to improve the dose accuracy for planning. In-house sandwich phantom was
used with MapCheck for planner dose verification. A PTW 0.6cc ion chamber was
included for absolute dose comparison. RESULTS: A copy of current machine data
with default highest dose rate is recommended. It is due to after 10th iteration
of optimization, the default dose rate will kick in. 2.5cm/s is the constraint
for Varian Millennium 120 MLC; a buffer zone of 10% is suggested to reduce the
MLC error on treatment. 2.25cm/s is used in our configuration. This results in
MLC interlock if not configured correct. Maximum leaf motion per gantry rotation
of 0.46cm/degree has to be checked for planning with Mosaiq R&V. Otherwise,
undeliverable plan will show up sometimes on 4DiTC.Tabletop was exported as a
DICOM structure from Eclipse to Pinnacle; we created a ROI template based on the
matched tabletop.QA using in-house phantom for different sites were tested.
Results for both planner dose and absolute chamber measurement are satisfactory.
CONCLUSIONS: Special attentions need to be paid for dose rate, MLC leaf speed,
leaf motion per gantry rotation when configuring SmartArc. Varian 21ex is
supported but is slow for clinical delivery. Users need to create your own
tabletop to improve planning accuracy. Conventional commission procedures for
RapidArc also apply for SmartArc.
PMID- 28517101
TI - SU-E-T-587: Whole IMRT, Hybrid IMRT and 3D Conformal Plan a Dosimetric Comparison
for Large Target.
AB - PURPOSE: To dosimetrically compare the whole-IMRT, hybrid-IMRT (combination of
IMRT and 3D-CRT) and 3D-conformal radiotherapy (3D- CRT) plans for larger
targets. METHODS: Five previously treated patients of carcinoma cervix with para
aortic lymph-nodes (target length 33-34cm) were selected. PTV-P (PTV-Primary),
PTV-PA (PTV-para-aortic) and organ at risks (OARs) were defined. Three plans were
generated using Eclipse TPS for Varian CL2300C/D linear accelerator using 6MV
photon beam. Three plans were: (i) Whole-IMRT: IMRT for both PTV-P and PTV-PA
(ii) Hybrid-IMRT: IMRT for PTV-P and 3D-CRT for PTV-PA (iii) 3D-CRT: 3D-CRT for
both PTV-P and PTV-PA. Prescription dose for PTV-P is 50.4Gy and PTV-PA is 45Gy
in 28 fractions. Coverage index (CI=Target volume covered by prescription
dose/Target volume), mean doses to bladder, rectum and bowel were used for plan
comparison by using DVH. Integral dose (liter-Gray) to normal tissue (i.e.,
patient volume minus PTV-P and PTV-PA) and total monitor units (MUs) required to
deliver a plan was also noted. RESULTS: The CI for PTV-P is 0.98+/-0.20, 0.96+/
0.09, and 0.95+/-0.01 for Whole-IMRT, Hybrid-IMRT and 3D-CRT plan and for PTV- PA
is 0.98+/-0.01, 0.98+/-0.01, and 0.97+/-0.20. Maximum doses to PTV-P are
5660.85+/-90.85cGy, 5640.35+/-70.35cGy and 5813.80+/-97.40cGy. Maximum doses to
PTV-PA are 5000.60+/-109.10cGy, 5079.85+/-20.25cGy and 5092.25+/-19.75cGy. Mean
doses to the bladder are 3810+/-225.80cGy, 3842.10+/-182.70cGy and 5204+/
98.25cGy for Whole-IMRT, Hybrid-IMRT and 3D-CRT plan, respectively. Mean doses to
rectum are 3955.35+/-324.95cGy, 3971.15+/-354.15cGy and 4741.20+/-371.60cGy. Mean
doses to bowel are 2623.35+/-320.85cGy, 2855.30+/-371.05cGy and 3011.7+/
433.80cGy. Average MUs required to deliver one fraction is 1285+/-87, 1585+/-186,
485+/-46 for Whole-IMRT, Hybrid-IMRT and 3D-CRT plans, respectively. Higher
integral doses to normal tissue were observed for whole-IMRT (267.60+/-76 liter
Gy) followed by hybrid-IMRT (259.20+/-53 liter-Gy) and 3D-CRT (186.30+/-33 liter
Gy). CONCLUSIONS: Whole-IMRT is useful for larger targets compared to hybrid-IMRT
in terms of dose conformity, lesser MUs and reduced critical organ doses with
little compromise on integral dose, where 3D-CRT sacrificed the OAR sparing.
PMID- 28517103
TI - SU-E-T-569: A Dosimetric Comparison of Helical Tomotherapy versus Intensity
Modulated Proton for Lung Cancer.
AB - PURPOSE: To evaluate the dosimetric difference between helical tomotherapy (HT)
and intensity modulated proton therapy (IMPT) treatment for lung cancer patients.
METHODS: Five patients treated by HT at University of Wisconsin Carbone Cancer
Center were selected. HT plans were generated on TomoTherapy treatment planning
station (TomoTherapy Inc., USA). The field widths were set to 2.5 cm for all
patients in this study. The IMPT plans were generated using the same planning CT
and contours with our in-house treatment planning system. Three to five field
spot scanning IMPT were used to deliver uniform doses to the targets while
minimizing the irradiated lung volume. The proton spots used has a Gaussian sigma
of 6mm and are placed on a rectangular grid. The dose distribution of each proton
spot is calculated using a pencil beam algorithm with tissue heterogeneity
corrections. All the dosimetric analyses are performed using normalized total
dose. Alpha/beta ratios were set to 3 for normal tissues and 10 for tumors.
RESULTS: IMPT plans showed improvement of critical structure avoidance and target
dose uniformity for all patients. Reductions in mean lung doses of between 81% to
27% were observed in the IMPT plans relative to the HT. The equivalent uniform
dose of the target improved from 49.2 Gy in HT plan to 60.04 Gy in IMPT for
patient #2, and equivalent for other cases. The maximum doses to cord were
reduced by 20.5 Gy on average using IMPT. In two patient cases, the normal tissue
complication probabilities were reduced by 53% and 14% with IMPT. CONCLUSION:
IMPT provides improved dose homogeneity on the target and normal structure
sparing compared with HT in the treatment of non-small cell carcinoma in lung.
Significant reduction of mean lung dose was demonstrated, as well as toxicity to
organs at risk adjacent to the target.
PMID- 28517104
TI - SU-E-T-609: Improving the Efficiency of VMAT Plan Optimization by Using Sparse
Decomposition Method.
AB - PURPOSE: Volumetric modulated arc therapy (VMAT) is capable of delivering highly
conformable dose distribution efficiently. Its planning is, however, more
computationally intensive and requires a huge amount of memory space for
optimization. We present an efficient sparse decomposition method for VMAT plan
optimization. METHODS: A quadratic objective function with volumetric constraints
is expressed as a function of the aperture shapes and weights of the incident
beams. The algorithm generates a sequence of iterates to solve the optimization
problem. Each step of iteratively reweighed method is to be updated by solving
the subproblem involving a quadratic (L2) term and a sparsity-inducing regulation
(L1) term. Through the sparse decomposition techniques of the given problem, the
deliverable apertures are directly generated. The shape of each aperture is
iteratively rectified to be a sequencing of arc using the manufacture
constraints. An initial arc spacing of 8 degree creates 45 beams directions for a
single arc, 360 degree. The angular separation is equispaced every 2 degree over
the end of optimization cycle. The optimization is implemented for a Varian
TrueBeamTM STX linac beams with and without flattening filters available. Three
clinical cases, head and neck, lung, and prostate, have been studied for the
purpose of evaluating the planning efficiency and quality of the plans. RESULTS:
The target dose coverage and critical structure sparing of VMAT plan are
comparable to those of IMRT plans. The VMAT plan delivers lower doses to other
OARs while keeping the similar target dose coverage to IMRT plan. The VMAT plan
optimizations takes less than 3 minutes on average of the cases indicating great
efficiency compared to existing methods. CONCLUSIONS: The results demonstrate
that the proposed method provides competent computational efficiency for
optimizing VMAT plan. The method substantially improves the speed and accuracy of
VMAT plan optimization and makes future on-treatment adaptive re-planning
possible.
PMID- 28517105
TI - SU-E-T-580: Does Arc Therapy Have the Potential to Improve Radiation Treatment of
Hodgkin's Lymphoma Patients?
AB - PURPOSE: To evaluate whether arc therapy (helical Tomotherapy and volumetric arc
therapy; VMAT) is superior to step and shoot IMRT regarding sparing of lungs
while maintaining adequate planning target volume (PTV) coverage in Hodgkin's
lymphoma patients . METHODS: Radiation treatment plans for eleven Hodgkin's
lymphoma patients were created employing the following techniques: coplanar and
noncoplanar Step & Shoot IMRT, VMAT and Tomotherapy, i.e., for every patient 4
different treatment plans were created. The IMRT and VMAT planning was performed
with Pinnacle software (v. 8 and 9, Philips) suitable for delivery with an Elekta
linear accelerator, Tomotherapy plans were calculated with Tomotherapy planning
software (v. 3.4). Four patients received a single prescription dose of 30 or 36
Gy, and 7 patients received a simultaneous integrated boost (30 Gy/36 Gy).
Treatment plans were optimized such that the normal tissue constraints for the
lung [volume receiving more than 20 Gy (V20) is less than 30% and mean lung dose
(MLD) is less than 14 Gy] were met, even if PTV coverage (V95%=99%) had to be
sacrificed. RESULTS: All 4 techniques delivered clinically acceptable treatment
plans. Tomotherapy achieved the highest dose homogeneity in the PTV and highest
dose coverage of the boost volume (on average 98% versus 96% for the other 3
techniques). Since lung sparing was the first planning objective, all techniques
scored equally well for V20 en MLD. CONCLUSIONS: The strength of arc therapy lies
in the large number of beamlets entering the patient from a high number of
angles. For Hodgkin's lymphoma patients this does not automatically translate
into a superior treatment due to the high weight on the lung objectives limiting
the number of beamlets allowed to pass through the lung. This means that for
Hodgkin's lymphoma arc therapy has no added value for sparing of the lungs.
PMID- 28517106
TI - Tunable Supramolecular Assembly and Photoswitchable Conversion of
Cyclodextrin/Diphenylalanine-Based 1D and 2D Nanostructures.
AB - A photocontrolled, interconvertible supramolecular 2D-nanosheet/1D-nanotube
system was constructed through the supramolecular assembly of adamantanyl
modified diphenylalanine with azobenzene-bridged bis(beta-cyclodextrin). The
nanosheet exhibited a greater fluorescence enhancement effect than the nanotube.
Significantly, these nanosheets and nanotubes could interconvert via the
photocontrolled trans/cis isomerization of azobenzene linkers in bis(beta
cyclodextrin), and this photo-switchable one-dimensional/two-dimensional
morphological interconversion was reversible and recyclable. This enables
convenient routes to highly ordered nanostructures with various morphologies and
dimensions that can be controlled by external stimuli.
PMID- 28517107
TI - Right coronary artery coronary sinus fistula with coronary sinus ostium stenosis.
AB - Coronary artery fistula (CAF) is a rare anomaly of the coronary artery. The
draining site of a right coronary artery (RCA) fistula may usually be the right
ventricle, right atrium, or pulmonary artery. Here, we present a patient with
right coronary artery to coronary sinus fistula (RCACSF) complicated by
aneurysmal dilatation of the coronary sinus (CS) and stenosis of CS ostium.
PMID- 28517108
TI - Goals of medical students participating in scholarly concentration programmes.
AB - OBJECTIVES: Scholarly concentration (SC) programmes are increasingly common in
medical school curricula, fostering student participation in mentored research.
Endpoints including publication rates and impact on career path have been
reported, but student goals have not been described. We describe how career plans
and gender impact the importance of students' SC-related goals. Understanding
student goals may enhance mentorship of professional development and self
directed learning skills. METHODS: First-year students at two US medical schools
were surveyed. Students reported intentions regarding career-long research and
specialty interests. Using a 5-point scale, students assigned importance to 13
goals (eight skill-related goals, four accomplishment-related goals and
mentorship), Composite scores for skills-related and accomplishment-related goals
were used for analysis. Regression analyses, controlling for school, were used to
determine whether intentions regarding career-long research, interest in highly
competitive residency or gender were associated with increased importance of
different goals. RESULTS: We surveyed 288 first-year medical students and
received 186 responses (64.6% response rate). Compared with their peers, students
interested in career-long research placed more importance on both skill-related
goals (beta coefficient, 1.87; 95% confidence interval [CI], 1.03-2.71; p <
0.001) and accomplishment-related goals (odds ratio [OR], 1.71; 95% CI, 1.09
2.69; p = 0.02). By contrast, compared with their peers, students interested in
highly competitive specialties placed more importance only on accomplishment
related goals (OR, 2.18; 95% CI, 1.15-4.11; p = 0.02). Compared with men, women
placed more importance on mentorship (OR, 2.47; 95% CI, 1.23-4.97; p = 0.01) and
were less likely to be interested in highly competitive residencies (39.4% versus
54.9%, p = 0.04). CONCLUSIONS: Gender and career plans are associated with
importance of SC-related goals in the first year of medical school. This
knowledge enables faculty to promote students' appreciation of important learning
goals in the setting of student research, which may help students engage in self
directed learning across their medical education.
PMID- 28517109
TI - The studies of ParA and ParB dynamics reveal asymmetry of chromosome segregation
in mycobacteria.
AB - Active segregation of bacterial chromosomes usually involves the action of ParB
proteins, which bind in proximity of chromosomal origin (oriC) regions forming
nucleoprotein complexes - segrosomes. Newly duplicated segrosomes are moved
either uni- or bidirectionally by the action of ATPases - ParA proteins. In
Mycobacterium smegmatis the oriC region is located in an off-centred position and
newly replicated segrosomes are segregated towards cell poles. The elimination of
M. smegmatis ParA and/or ParB leads to chromosome segregation defects. Here, we
took advantage of microfluidic time-lapse fluorescent microscopy to address the
question of ParA and ParB dynamics in M. smegmatis and M. tuberculosis cells. Our
results reveal that ParB complexes are segregated in an asymmetrical manner. The
rapid movement of segrosomes is dependent on ParA that is transiently associated
with the new pole. Remarkably in M. tuberculosis, the movement of the ParB
complex is much slower than in M. smegmatis, but segregation as in M. smegmatis
lasts approximately 10% of the cell cycle, which suggests a correlation between
segregation dynamics and the growth rate. On the basis of our results, we propose
a model for the asymmetric action of segregation machinery that reflects unequal
division and growth of mycobacterial cells.
PMID- 28517110
TI - Outcomes after medical and surgical interventions in horses with temporohyoid
osteoarthropathy.
AB - BACKGROUND: Temporohyoid osteoarthropathy (THO) is a cause of neurological
disease in horses that is characterised by facial and vestibulocochlear nerve
deficits. Studies reporting and comparing survival following medical or surgical
treatment of THO are lacking. OBJECTIVES: To compare survival and prognosis in
horses with THO treated medically or surgically, and to report surgical
complications. STUDY DESIGN: Retrospective study. METHODS: The medical records of
horses diagnosed with THO were retrieved, and data on signalment, clinical signs
and duration, corneal ulceration and bilateral occurrence were recorded.
Neurological severity was graded according to clinical signs. Preoperative
radiographic and endoscopic images were graded according to the severity of
changes. Factors potentially affecting survival and treatment were compared using
Cox proportional hazards regression. RESULTS: A total of 77 horses were
identified as having THO during the period 1990-2014. Of these, 25 horses
underwent ceratohyoid ostectomy (CHO) and eight underwent partial stylohyoid
ostectomy (PSHO). Thirteen of 20, one of 25 and one of eight horses treated by
medical therapy, CHO and PSHO, respectively, died or were subjected to euthanasia
as a consequence of THO. Compared with CHO, medical therapy was significantly
associated with nonsurvival, but there were no significant differences in
survival between horses undergoing PSHO and medical therapy. The duration of
clinical signs, and neurological, radiographic and endoscopic grades were not
associated with survival of THO. However, the age of the horse was significantly
associated with poorer survival. Survival time was significantly shorter in the
medical therapy group compared with the two surgical groups combined, but did not
differ significantly between the two surgical groups. No significant difference
between groups was seen in the incidence of surgical complications (33.3% in the
PSHO and 22.2% in the CHO group). MAIN LIMITATIONS: This was a nonrandomised
study of treatment effects on survival and included a low number of cases.
CONCLUSIONS: The survival prognosis in horses with THO is good to excellent in
those submitted to surgical intervention, and fair in those treated with medical
therapy alone.
PMID- 28517112
TI - Patterns and correlates of adherence to self-monitoring in lung transplant
recipients during the first 12 months after discharge from transplant.
AB - Self-monitoring of lung function, vital signs, and symptoms is crucial for lung
transplant recipients (LTRs) to ensure early detection of complications and
prompt intervention. This study sought to identify patterns and correlates of
adherence to self-monitoring among LTRs over the first 12 months post-discharge
from transplant. This study analyzed existing data from the usual care arm
participants of a randomized clinical trial who tracked self-monitoring
activities using paper-and-pencil logs. Adherence was calculated as the percent
of days LTRs recorded any self-monitoring data per interval: hospital discharge-2
months, 3-6 months, and 7-12 months. The sample (N=91) was mostly white (87.9%),
male (61.5%), with a mean age of 57.2+/-13.8 years. Group-based trajectory
analyses revealed two groups: (i) moderately adherent with slow decline (n=29,
31.9%) and (ii) persistently nonadherent (n=62, 68.1%). Multivariate binary
logistic regression revealed the following baseline factors increased the risk in
the persistently nonadherent group: female (P=.035), higher anxiety (P=.008), and
weaker sense of personal control over health (P=.005). Poorer physical health
over 12 months were associated with increased risk in the persistently
nonadherent group (P=.004). This study highlighted several modifiable factors for
future interventions to target, including reducing post-transplant anxiety, and
strengthening sense of personal control over health in LTRs.
PMID- 28517114
TI - SU-E-T-108: 3D Measurement of Neutron Dose from a Novel Neutron Imaging
Technique.
AB - PURPOSE: We have been developing a fast-neutron spectroscopic technique to
quantitatively image the distribution of elements in the body using quasi
monochromatic neutron beams. Previously, we demonstrated the ability of the
technique to quantify specific elements in the liver and breast while limiting
radiation dose to clinically acceptable levels. Here we present the results of a
physical dose measurement performed through neutron irradiation of 3D PRESAGE
dosimetry phantoms. METHODS: Two PRESAGE optical-CT dosimeters were placed inside
a physical phantom of the human torso and irradiated with 8 MeV neutrons produced
via the 2H(d,n) reaction using a tandem Van-de-Graaff accelerator. The
dosimeters, measuring 10 cm and 4 cm in diameter, were located in regions
corresponding to the liver (10 cm), and the kidney (4 cm). Irradiation was
performed with the neutron beam incident directly on the larger dosimeter.
Cumulative neutron fluence incident upon each dosimeter was determined using an
aluminum-foil activation technique. Following irradiation, the change in optical
density in both dosimeters was measured to determine the relative irradiation and
dose distribution in each volume. RESULTS: Both PRESAGE dosimeters exhibited
detectable changes in optical density corresponding to the dose deposited in the
volume. The two dosimeters registered doses of 8.5 Gy (direct incidence, 4.5 hour
irradiation) and 0.25 Gy (off-axis, 20 hour irradiation), respectively. The
larger dosimeter showed highest intensity at the entry point of the beam with
exponential drop-off along the beam direction. The smaller dosimeter registered a
more uniform change in intensity, consistent with the higher incidence of
scattered neutrons at this location. CONCLUSION: The results demonstrate the
utility of PRESAGE dosimeters in measuring dose from neutron irradiation and
highlight the difference in relative doses between primary and proximal organs
when exposed to neutron beams. This work was supported by the United States
Department of Energy, Office of Nuclear Physics under Grant No. DE-FG02
97ER41033, the National Cancer Institute under grant R01CA100835, and by the
Department of Defense under award W81XWH-09-1-0066.
PMID- 28517113
TI - Differences between two strains of Ceriporiopsis subvermispora on improving the
nutritive value of wheat straw for ruminants.
AB - AIM: This study evaluated differences between two strains of Ceriporiopsis
subvermispora on improving the nutritive value and in vitro degradability of
wheat straw. METHODS AND RESULTS: Wheat straw was treated with the fungi for 7
weeks. Weekly samples were analysed for ergosterol content, in vitro gas
production (IVGP), chemical composition and lignin-degrading enzyme activity.
Ergosterol data showed CS1 to have a faster initial growth than CS2 and reaching
a stationary phase after 3 weeks. The IVGP of CS1-treated wheat straw exceeded
the control earlier than CS2 (4 vs 5 weeks). CS1 showed a significantly higher (P
< 0.001) selectivity in lignin degradation compared to CS2. Both strains showed
peak activity of laccase and manganese peroxidase (MnP) at week 1. CS1 showed a
significantly higher (P < 0.001) laccase activity, but lower (P = 0.008) MnP
activity compared to CS2. CONCLUSION: Both CS strains improved the nutritive
value of wheat straw. Variation between strains was clearly demonstrated by their
growth pattern and enzyme activities. SIGNIFICANCE AND IMPACT OF THE STUDY: The
differences among the two strains provide an opportunity for future selection and
breeding programs in improving the extent and selectivity of lignin degradation
in agricultural biomass.
PMID- 28517116
TI - SU-E-T-91: Validation of Geant4 Physics for Ionization Chamber Calculations in
Radiotherapy Photon Beams.
AB - PURPOSE: To determine the accuracy of the GEANT4 Monte Carlo toolkit for
ionization chamber calculations in radiotherapy photon beams. METHODS: First, we
used the Fano cavity example included in the GEANT4 distribution to validate
calculations under Fano conditions. We determined a combination of parameters and
physics list that provided results consistent within +/- 0.5% with the Fano
theorem. Next we performed simulations to investigate the accuracy of using
GEANT4 for ionization chamber calculations. Eight ionization chambers were
modeled using detailed manufacturer specifications including A1, A1SL, NE2571,
PTW30010, PTW30012, PTW31010, PTW31014 and PTW31016. The absorbed dose to water
for a cylindrical water cavity and the absorbed dose to air in the ionization
chambers' cavities were scored for 1.25 MeV photons. The ratio of these
quantities was then compared to values from EGSnrc simulations. RESULTS:
Simulations using the Fano cavity example yielded results within +/- 0.5% with
the Fano theorem across 1.25, 3 and 4 MeV incident photon energies. The most
accurate and consistent results were obtained using the G4eIonisation ionization
model and G4GoudsmitSaundersonMscModel multiple scattering (MS) model with a
maximum step size limitation of 0.001 mm, which yielded results accurate to +/-
0.3% for all energies. This set of parameters and physics processes as well as
the G4UrbanMscModel93 MS model were used for the ionization chamber calculations.
The calculated quantities were compared to those used in Muir and Rogers 2010
(Med. Phys. 37: 5939-5950) and agreed to within sub-percentage differences for
most chambers. CONCLUSIONS: The GEANT4 toolkit can achieve sub-percentage
accuracy for ionization chamber calculations in radiotherapy photon beams. This
is achieved by using either the G4GoudsmitSaundersonMscModel or G4UrbanMscModel93
MS models. Although less accurate (+/- 0.5%), simulations employing the
G4UrbanMscModel93 MS model are on average two orders magnitude faster than that
of the G4GoudsmitSaundersonMscModel MS model (+/- 0.3%). Natural Sciences and
Engineering Research Council of Canada.
PMID- 28517115
TI - SU-E-T-119: Evaluation of New VMAT and IMRT Planning QA Devices: Portal Dosimetry
Vs Compass.
AB - PURPOSE: Wide spread clinical use of advanced radiation treatment delivery
techniques such as volumetric modulated arc therapy (VMAT) and IMRT needs an easy
to-use, well-defined, and effective quality assurance (QA) system to ensure the
accuracy of dose delivery. The comprehensive evaluation of two delivery QA
systems (DQA) (Portal Dosimetry and Compass) for the advanced radiation delivery
techniques is necessary for the clinical setting. METHODS: Portal Dosimetry QA
system with Varian PortalVision (PV) provides a quantitative comparison of
measured electronic dose profile to a predicted dose profile with Varian's
EclipseTM treatment planning system (TPS) for the VMAT and IMRT plans.
Quantitative comparisons of the two images, including dose difference, gamma
analysis, points dose measurements, and line profiles are easily acquired in two
dimensions. Meanwhile, Compass system with MatriXX can provide an accurate three
dimensional quantitative analysis of dose delivery. We applied the two planning
QA systems to our RapidArc patient- specific QAs. Validation of the Compass and
Portal Dosimetry systems were performed with ionization chamber measurements for
absolute dosimetry and film measurements for gamma index calculations for phantom
and patient treatment plans. RESULTS: Compass system was very sensitive to the
MLC leaf gap variations in three dimensional gamma analyses. However, Compass
system was not enough to fix the errors in dosimetric leaf gap by itself. DQA
process with Portal Dosimetry took approximately 6 minutes for the two Arcs VMAT
plan. Compass took about 40 minutes for the same plan in our first clinical
trial. For the three typical IMRT and VMAT plans, the two systems showed the same
passing rates in 95% pixels passing gamma criteria 3%/3mm. CONCLUSIONS: Portal
Dosimetry DQA system has the advantages of effectiveness and practicality in the
clinical setting. On the other hand, Compass was the next supportive system
because of its accuracy and reality with patient's anatomy.
PMID- 28517117
TI - SU-E-T-130: IMAT Patient Specific Quality Assurance Using ArcCHECK Diode Array
Detector.
AB - PURPOSE: To evaluate the IMAT patient specific quality assurance (QA) performed
using ArcCHECK detector array in reference with standard ion chamber for routine
clinical use. METHODS: Twelve patient plans having different tumor sites chosen
for this study. On Eclipse planning system,IMAT patient plans were calculated on
ArcCHECK phantom inserted with Ion chamber using superposition algorithm.
ArcCHECK is a cylindrical phantom with a three-dimensional array of 1386 diode
detectors, arranged in a spiral pattern, with 10 mm diode spacing. These plans
delivered from Clinac-iX linac equipped with 120 MLC. Point dose and Dose/fluence
map were measured simultaneously with ion chamber (IC-15) and ArcCHECK diode
array detector respectively. Point doses, dose/fluences map and dose at central
axis (CAX) on ArcCHECK phantom were compared with their respective TPS calculated
values. RESULTS: The ion chamber measurements are in good agreement with TPS
calculated doses. Mean difference between them is 0.50% with standard deviation
is 0.51%. Concordance correlation coefficient (CCC) obtained for ion chamber base
absolute dose measurements is 0.9996. These results demonstrate a strong
correlation between the absolute dose predicted by our TPS and the measured dose.
The precision of the TPS software was 0.9999, and its accuracy was 0.9997.The
agreement between ArcCHECK doses and TPS predictions on the CAX, shown CCC of
0.9978 (the mean difference in the central axis dose is 2.11%). The 95%
Confidence Interval is from 0.9932 to 0.9995. In gamma analysis of dose/fluence
map the mean passing rate was 98.53% for 3% dose difference and 3mm distance to
agreement. CONCLUSIONS: The IMAT patient specific QA with Ion chamber and
ArcCHECK phantom are consistent with the TPS calculated dose. Statistically good
agreement observed between ArcCHECK measured and TPS calculated. Hence it can be
used for routine IMAT QA.
PMID- 28517118
TI - SU-E-T-101: Dosimetry Intercomparison for a Synchrotron-Produced Monochromatic X
Ray Beam.
AB - PURPOSE: This study performed a dosimetry intercomparison for synchrotron
produced monochromatic x-ray beams. Ion chamber depth-dose measurements in a
polymethylmethacrylate (PMMA) phantom were compared with the product of MCNP5
Monte Carlo calculations of dose per fluence and measured incident fluence at 25
and 35 keV. The ion chamber measurements are being used to calibrate dose output
for cell irradiations designed to investigate photoactivated Auger electron
therapy at the LSU Center for Advanced Microstructures and Devices (CAMD)
synchrotron facility. METHODS: Monochromatic beams of 25 and 35 keV were
generated on the tomography beamline at CAMD. A cylindrical, air-equivalent ion
chamber was used to measure the ionization created in a 10*10*10-cm3 PMMA phantom
at depths of 0.6 - 7.7 cm. AAPM TG-61 protocol was applied to convert measured
ionization into dose. MCNP5 simulations of the irradiation geometry were
performed to determine the dose deposition per photon fluence in the phantom.
Photon fluence was determined using a NaI detector to make scattering
measurements of the beam from a polyethylene target at angles 15 - 60 degrees.
Differential Compton and Rayleigh scattering cross sections were used to derive
the incident fluence. RESULTS: At 35 keV dose measurements for equal exposures
determined using the MCNP5-fluence results underestimated those of the ion
chamber by 1.8 - 4.8% for PMMA depths from 0.6 - 7.7 cm, respectively. At 25 keV
there was an overestimate of 6.6 - 1.9%. CONCLUSIONS: These results show that TG
61 ion chamber dosimetry, used to calibrate the dose output for the cell
irradiations, is accurate within approximately 7% for beam energies 25-35 keV.
This research was supported by contract W81XWH-10-1-0005 awarded by The U.S. Army
Research Acquisition Activity, 820 Chandler Street, Fort Detrick, MD 21702-5014.
This report does not necessarily reflect the position or policy of the
Government, and no official endorsement should be inferred.
PMID- 28517119
TI - SU-E-T-141: Dosimetry and Error Analysis of HDR Brachytherapy Tandem Applicator
Using A16 Microchamber and Monte Carlo Simulation.
AB - PURPOSE: Absolute dosimetry with the associated uncertainties for 192Ir High Dose
Rate (HDR) Brachytherapy Tandem applicator are presented using A16 microchamber
and Monte Carlo simulation. The results are compared to the TG-43 protocol.
METHODS: An A16 Exradin MicroChamber, MCNPX 2.6 Monte Carlo simulation code and
PTW farmer chamber with an ADCL calibration coefficient were used in this work.
The A16 microchamber was calibrated using MCNPX simulation and PTW farmer
chamber. Statistical and systematic uncertainty analyses associated with each
experimental technique were analyzed quantitatively using MCNPX 2.6 to evaluate
source positional error, Tandem positional error, phantom size effect, volume
averaging, stem and wall effects, and Tandem effect. RESULTS: A16 microchamber
was calibrated according to the AAPM TG-21 protocol and resulted in a value of
3.21E+09 Gy/C for Ngas in 60CO. To use the A16 with 192Ir spectrum, a correction
factor of 1.13 was generated along the source transverse axis using MCNPX to
account for energy difference. Absolute dose and uncertainty analyses along the
transverse axis of a Tandem applicator were calculated using MCNPX and A16
microchamber and compared to the TG-43 protocol. The generated overall
uncertainties associated with the A16 microchamber are 22%, 17%, 15%, 15%, 16%,
17%, and 19% at 1cm, 2cm, 3cm, 4cm, and 5cm, respectively. CONCLUSIONS: In this
work, the author investigated the absolute dosimetry for 192Ir HDR brachytherapy
for a Tandem applicator using A16 microchamber and compared the results to the TG
43 protocol. A16 microchamber has an effective volume of 0.007cc which makes it
suitable to measure extremely small field sizes and enables high spatial
resolution while minimizing volume averaging near the source. Furthermore, the
author also investigated and analyzed the systematic and statistical
uncertainties associated with A16 experimental dosimetry as recommended by AAPM
TG-138 and GEC-ESTRO. Based on this work, dosimetry of HDR brachytherapy using
A16 microchamber can be used, within uncertainties, as an alternative or
redundant for the LiF TLDs.
PMID- 28517120
TI - SU-E-T-144: Daily and Monthly Quality Assurance with TomoDose.
AB - PURPOSE: Examine the use of TomoDose for Tomotherapy quality assurance. METHODS:
Baseline TomoDose profiles are acquired annually in accordance with TG-148.
During monthly quality assurance, TomoDose is irradiated with a static beam and
referenced to baseline. Differences between superimposed profiles are evaluated
monthly. TomoDose is further utilized in verifying transverse laser alignment.
The TomoDose is aligned to virtual isocenter lasers and statically irradiated
with a 40cm * 5.02cm treatment beam. Next, the TomoDose's internal diodes are
imaged using the MVCT. Transverse laser, imaging beam, and treatment beam field
center are verified to less than 1mm coincidence difference. For daily TomoDose
irradiation the couch is set to a fixed height and irradiated. The dose to the
central axis and dose rate is recorded. To check energy, the measurement is
repeated with an aluminum block placed centrally on the TomoDose. The output
reading relative to the dose rate is compared to the baseline determined at the
time of monthly verification. A ratio of the output and energy readings serves as
a daily energy constancy check. RESULTS: Over 28 months, for nominal field sizes
of 1.05, 2.50, and 5.02cm, TomoDose measured an average field size of 1.10, 2.51,
and 5.02cm with maximum deviations of 0.09, 0.09, and 0.10cm, respectively. For
transverse laser alignment, TomoDose software calculates beam center location. We
have found the alignment to be sensitive to sub-millimeter changes. Our nominal
daily energy ratio is 0.689. We have observed a decline from an estimated 0.693
to 0.680 with target wear, providing a good indicator of degradation.
CONCLUSIONS: TomoDose serves as a reliable constancy device with added benefits
of verifying transverse laser alignment and predicting target health. I own
common stock in Accuray (Tomotherapy).
PMID- 28517121
TI - SU-E-T-93: High Dynamic Range Scanning for Optical-CT in 3D Dosimetry.
AB - PURPOSE: The recent emergence of powerful, fast and high-resolution 3D dosimetry
techniques brings exciting potential to radically strengthen the foundations of
quality-assurance in radiation therapy, and hence treatment efficacy. This work
presents a new acquisition method for 3D dosimetry by optical-computed-tomography
(optical-CT), which can improve accuracy when imaging strongly attenuating
dosimeters (e.g. large or heavily dosed). METHODS: The method involves acquiring
optical-CT projection images where the intensity of the light source is increased
as much as possible without causing detector saturation within the dosimeter.
This improves signal-to-noise in dark regions of the dosimeter, but flood-field
and regions outside the dosimeter are unuseable due to saturation. The problem of
acquiring a useable flood is solved by acquisition at a reduced shutter opening
time. The non-saturated flood is then scaled up for use with projections, by the
ratio of shutter times. The method relies on linearity of signal with shutter
time, which is investigated here. The method is evaluated by application to a
range of dosimeters with varying degrees of strong attenuation. RESULTS: The
relationship between signal and shutter time in the flood was found to be highly
linear, a key enabling result for this method. When applied to moderately
attenuating dosimeters, the new method agrees with the standard method to a high
degree (<1% deviation on average). For very dark dosimeters, the new method was
found to have greatly improved signal-to-noise (a factor of 2-3 times better) in
the darkest regions and eliminated streak artifacts present in reconstructions
using the standard acquisition method. CONCLUSIONS: A new optical-CT acquisition
method is presented which yields improved signal-to-noise for dosimetry
measurements in strongly attenuating dosimeters. A further important advantage is
the method does not require any tinting of the refractively-matched fluid in the
optical-CT water-bath, which greatly increases convenience and practicability.
Grant - R01CA100835.
PMID- 28517122
TI - SU-E-T-132: Investigation of Photon and Proton Overlapping Fields in PRESAGE-
Dosimeters.
AB - PURPOSE: To evaluate the effects of overlapping dose volumes for varying field
arrangements in two formulations of PRESAGE(r): one intended for, and irradiated
with, proton beams and the other photon beams. METHODS: For each treatment
modality (photon, proton), three overlapping field setups were performed. These
included a stationary dosimeter irradiated over six fractions, a dosimeter
shifted laterally to the field to deliver a dose plateau in two fractions, and a
dosimeter rotated on its axis to deliver a two-field (for protons) and four-field
(for photons) box treatment overlapping in the center of the dosimeter. All
subsequent fractions were given within ten minutes and never less than one minute
apart. Two cylindrical PRESAGE(r) dosimeters approximately 7.5 cm in length by
7.5 cm in diameter were irradiated for each setup. The dosimeters were paired,
with one dosimeter given total dose by a single fraction while the other followed
one of the overlapping field setups. The dosimeters were analyzed using an
optical CT scanner and exported to the CERR environment where the doses were
compared between paired dosimeters. RESULTS: Dose profile comparisons showed
relative dose agreement between paired dosimeters within 5% along the SOBP region
of the proton formulation. In the case of the fractionated proton irradiation,
there was an over-response while other setups resulted in under-responses. Dose
agreement between the photon dosimeter treated with six fractions showed a dose
under-response within 11% and never less than 5%. Future measurements will
include the remaining field setups. CONCLUSIONS: The proton formulation of
PRESAGE(r) showed good dose agreement between single and multiple field
irradiations. While the photon formulation had slightly less agreement,
additional field setup comparisons may show improved results. These results will
aid future measurements of overlapping field treatment plans delivered to
PRESAGE(r) for treatment verification for proton and photon 3D dosimetry.
PMID- 28517123
TI - SU-E-T-103: Three-Dimensional Measurements of Dose and LET from a Proton Beam via
Polymer Gel Dosimetry.
AB - PURPOSE: To obtain and assess the accuracy of 3D dose distributions and LET maps
from a passively-scattered proton beam through the use of LET-dependent and LET
independent polymer gel formulations. METHODS: Dose measurements were performed
with BANG3-Pro2 (MGS Research, Inc, Madison, CT) polymer gel dosimeters. The
dosimeters were mixed from kits and were poured into 14.5 cm high by 15 cm
diameter acrylic cylinders. For LET measurements, a new BANG3-Pro variant
intended for use as an 'LET- meter' was employed. Initial irradiations were
performed using a 200 MeV passively scattered proton beam with a 4 cm spread out
Bragg peak (SOBP), delivering a physical dose of 3 Gy to the center of the SOBP.
Dosimeters were read out using the OCTOPUS-IQ (MGS Research, Inc, Madison, CT)
optical CT scanner. The optical densities measured in the gel were compared
against ion chamber data to assess the accuracy of the dosimeter. RESULTS:
Initial analysis indicates 80% of points measured along the central axis agreed
with ion chamber data at the +/-5%/+/-3mm level in the sensitive region of the
gel. An artifact in the reconstructed image produced inaccurate readings beyond
the depth of 50% dose on the distal edge of the SOBP, resulting in the majority
of the agreement failures. CONCLUSIONS: BANG3-Pro2 polymer gel dosimeters
demonstrate promise as a 3D dosimeter for use in proton therapy. The dosimetric
data obtained to date will be used as the baseline measurement against which the
LET-sensitive BANG3-Pro formulation will be compared for the measurement of
proton LET.
PMID- 28517124
TI - SU-E-T-114: Characterization of the Spatial Response Functions of Ionization
Chambers for Photon Beam Dosimetry.
AB - PURPOSE: The finite extension of an ionization chamber gives rise to a spatial
averaging effect, known as the "volume effect". In order to provide the
appropriate corrections, the response functions along its lateral and
longitudinal directions are characterized using Gaussian distributions, whose
standard deviations slat and slong have been determined for a large set of
clinical dosimeters. METHODS: Nine cylindrical ionization chambers, two parallel
plate chambers and two 2D ionization chamber arrays have been examined by
scanning rectangular photon fields along their short axes. The true profiles D(x)
were known from scans with a small Si diode. The ionization chambers were aligned
with their symmetry axes either perpendicular or parallel to the scan direction
in order to obtain slat and slong separately. In a search process, D(x) was
numerically convolved with normalized one-dimensional Gaussian kernels K(x) of
varying s. The best fit between the convolution product D(x) * K(x) and the
measured profile M(x) of the ionization chamber was used to determine parameters
slat and slong of the Gaussian kernels. RESULTS: For both the lateral and
longitudinal directions, very good agreement was found between M(x) and the
convolution products of D(x) with Gaussian kernels K(x). For all chambers, their
2s values are similar to the cavity dimensions, which means that the "tails" of
the Gaussian response functions reach into the exterior of the chambers, - an
effect of the ranges of the secondary electrons. At higher photon energies
response functions K(x) are slightly wider, but no detectable depth dependence
has been observed. CONCLUSIONS: We have shown that the response functions of
ionization chambers can be described by Gaussian distributions, confirming
earlier observations, and we determined their standard deviations in both the
lateral and longitudinal directions. Using these response functions, appropriate
correction methods determined to eliminate the volume effect can be applied.
PMID- 28517125
TI - SU-E-T-86: Development and Implementation of the Use of Optically Stimulated
Luminescent Detectors in the Radiological Physics Center Anthropomorphic Quality
Assurance Phantoms.
AB - PURPOSE: To study the angular dependence of optically stimulated luminescence
dosimeters (OSLD) in the Radiological Physics Center anthropomorphic quality
assurance pelvic phantom to provide accurate dosimetric measurements as a
replacement for TLD. METHODS: A spherical phantom was constructed to investigate
the angular response of the OSLD as oriented in the RPC pelvic phantom. Three
OSLD per irradiation angle, placed at the center of the spherical phantom, were
irradiated with 100 cGy from six different angles. The angular response at each
angle was determined relative to the OSLD response when the beam was incident
normally on the OSLD surface. A pelvic phantom dosimetry insert was modified to
include both TLD and OSLD. Three treatment plans were developed in Pinnacle v9.0
and one in Accuray's Multiplan, each with increasing angular beam delivery (4
field, IMRT, SmartArc, CyberKnife) for the pelvic phantom using a common dose
prescription and constraints. Each plan was delivered to the phantom three times,
containing two TLD and two OSLD, oriented in the transverse plane, at the center
of the PTV. The dose delivered to the TLD and OSLD was calculated for each
treatment and then compared. RESULTS: The angular dependence correction factor
for the spherical phantom was found to be uniformly 1.041 +/- 0.003 from single
beam edge-on irradiations. The angular dependence correction in the pelvic
phantom from multiple beam orientation irradiations was 1.024 +/- 0.002, such
that the OSLD dose agreed with the TLD dose. Applying the OSLD pelvic phantom
correction factor, the RPC measured dose to planning system calculated dose ratio
was 0.995 +/- 0.009. The established RPC phantom TLD dose to calculated dose
ratio was 0.995 +/- 0.010. CONCLUSIONS: An anthropomorphic phantom OSLD angular
dependence correction factor was established such that the final OSLD dose
measurements agreed with RPC's TLD dose measurements to within 1%. Work supported
by grant CA 10953, awarded by NCI, DHHS.
PMID- 28517126
TI - SU-E-T-125: High-Resolution Linear Diode Array for Use in Stereotactic Beam
Commissioning.
AB - PURPOSE: Task Group 106 discusses detector arrays and their usefulness in "soft
wedge" profile measurements. This study verifies an extension of their use; where
a high-resolution linear diode array is used to measure profile scans for use in
commissioning stereotactic beam. Small-field data is acquired with the LDA-99sc
(IBA Dosimetry America, Memphis, TN), an array of 99 two-mm-diameter Hi-pSi
diodes. These data are compared to data collected during serial scanning with an
IBA SFD stereotactic diode. METHODS: Field measurements were taken at varying
depths using an LDA-99sc in 1*1 cm2 , 2*2cm2 , and 3*3cm2 fields of a Trilogy
accelerator (Varian Medical Systems, Palo Alto, CA). These scans were duplicated
in resolution and sample rate with an SFD scanning diode. Both techniques
acquired point data in 1.0mm increments. RESULTS: In identical conditions, the
LDA-99sc provided readings with significantly less signal fluctuation than with
traditional diode scanning; which is attributed to the reduction of water motion
associated with detector travel during traditional scanning. This smoother data
precluded the use of smoothing and filtration algorithms; allowing the beam to be
modeled using raw data. The LDA-99sc measured an average penumbra of 0.1 mm wider
than that which was measured with the diode. The LDA-99sc also measured an
average field size of 0.3mm wider than that which was measured with the diode.
With respect to time, a single profile scan (30cm-depth, 3*3cm2 field) using the
LDA-99sc took 31 seconds, while a diode scan took 229 seconds. CONCLUSIONS: The
LDA99 provided accurate commissioning-grade small-field beam profile data, as
verified by comparison with diode scans, with a reduction of uncertainty in
readings and a substantial reduction in time. Variation in penumbra and beam
widths were deemed acceptable and can be attributed to the LDA-99sc data being
raw, while the diode data was processed. Research supported in-part by IBA
Dosimetry America.
PMID- 28517127
TI - SU-E-T-97: Intra and Inter Variability in Beam Data Commissioning among Water
Phantom Scanning Systems.
AB - PURPOSE: There are many water-phantom scanning systems with advanced features to
collect accurate commissioning data. However the intra- and inter-variability of
commissioning data has not been reported which is attempted in this study.
METHODS: Four vendors with modern water-phantom scanning systems; PTW, Sun
Nuclear (SN), Standard Imaging (SI) and IBA were invited to an institution to
demonstrate beam data collection. Each system was used to collect percent depth
dose (PDD) and profiles several times in a day with their choice of detector for
four different machines for photon and electron beam commissioning. This provided
information on intra-variability. At the end, each vendor was allowed to setup
and collect data on a single unit for inter-variability. All data were sent to a
central location for analysis and evaluation. RESULTS: The depth dose and
profiles for 2*2cm2 and 10*10cm2 fields were analyzed for intra- and inter
variability. With repeated measurements, the intra-variability provided a
detailed degree of fidelity of data collection. This was shown to be with (+/-
0.1%) among all vendors. Ignoring data in buildup region and comparing with one
system (PTW), the PDDs variability were slightly larger 0.02+/-0.17%, 0.14+/
0.21%, 0.17+/-0.2%, for SI, SN and IBA, respectively. The profiles inter
variability in central region were <0.1 %, however in penumbra up to +/- 4.8%were
observed. The polarity effect was also noted up to 3% which was depth and
detector dependent. CONCLUSIONS: Intra- and inter-variability among various
scanning system are very small indicting that all modern systems if used properly
could collect data within+/-0.2% accuracy. The selection of device should be
based on institutional comfort and personal preference of software and hardware.
This study provides unique opportunity to compare data among systems which is
otherwise not possible.
PMID- 28517128
TI - SU-E-T-136: Comparison of TomoScannerTM 2D Water Phantom versus IBA Helix for
Tomotherapy Profile Measurements.
AB - PURPOSE: To compare the differences in measured data using Tomotherapy's
TomoScannerTM 2D Water Phantom versus IBA's Blue Phantom Helix taken during
commissioning of the Tomotherapy HD unit. METHODS: IBA Helix was used with CC04
ion chamber to measure Inline (jaw-size width), Crossline (40 cm width) and
Percent Depth Dose (PDD). Data was analyzed using IBA Omni-Pro 7.3 software.
Measurements were performed at 85 SSD for field sizes 5*40 cm2 , 2.5*40 cm2 , and
1.0*40 cm2 . All field sizes were measured at 1.5 cm (nominal dmax), 5 cm, 10 cm
and 15 cm depths. Scans were performed at a continuous speed setting of 0.5
cm/sec. Setup and data measurements were performed twice on separate occasions
for consistency and repeatability. Data measurements were normalized to 10 cm
depth and compared to commissioning data taken from TomoScannerTM and
Tomotherapy's Twinning Data. RESULTS: For all jaws, the profiles measured at 5
cm, 10 cm, and 15 cm depth using IBA Helix matched the profiles of the
TomoScannerTM data within 1%. Profile variance at 1.5 cm depth showed a deviation
of up to 3%. For all jaws, the PDD comparisons displayed 3-5% deviation from the
surface to 2 cm depth and within 1% deviation at 2 cm to 15 cm depth.
Measurements performed using CC04 ion chamber versus A1SL ion chamber (used by
Standard Imaging) showed data differences of less than 0.5%. CONCLUSIONS:
Discrepancies in Tomotherapy beam profiles were observed between different water
phantoms. Further investigation is required to determine the cause of variances
between IBA and Tomotherapy data sets such as investigating geometrical
differences between the water tanks and software dissimilarities in collecting
and correcting raw data. It is recommended that independent commissioning data be
taken when TomoScannerTM is not the clinical site's standard water phantom.
PMID- 28517129
TI - SU-E-T-107: Uncertainty Estimate of a Practical EBT-2 Film Dosimetry Approach:
Transpose-And-Scan Technique.
AB - PURPOSE: To estimate the uncertainty of a practical EBT2 film dosimetry approach
that has been established at our institution and used for routine patient
specific plan verifications, particularly for SBRT and RapidArc, as well as
planning system commissioning. Our technique is unique from other common
dosimetry protocols with respect to calibration, irradiation and scanning.
METHODS: Film dosimetry for patient-specific quality assurance of 29 patient
plans were retrospectively reviewed. For each case, four films were irradiated;
two for calibration and two for treatment plan. Each pair of two films were
irradiated together in a phantom with one film transposed (rotated 180 degrees
relative to the other) to compensate for asymmetric film response. After a
minimum of 12 hrs post-irradiation, each film was scanned in four different
orientations to mitigate non-uniform response of the scanner light and detector
elements. The scanned 8 calibration and 8 plan images were averaged into one
calibration and one plan film image, respectively. Each color channel of the
calibration film was correlated to the reference dose matrix to produce a 3rd
order polynomial calibration curve. Finally, each color channel of the plan film
was converted to a dose map using the corresponding calibration curve. Average
dose maps of the red and green channels were correlated to the treatment planning
dose matrix, and the mean dose differences at the center of dose distributions
(5*5mm2 area) as well as a gamma analysis were evaluated. RESULTS: The absolute
dose differences were -0.8+/-1.7% (range=-4.5-3.0%). The gamma pass-rates
(3%/3mm) were 94+/-7% (min.=74%). The pass rate increased to 99+/-3%(min.=87%)
with the film scaled relatively to the plan doses. CONCLUSIONS: Based on a large
number of cases, our approach appears to be robust to non-uniform film and
scanner responses, and is shown to have an uncertainty (1SD) of less than 2% for
absolute film dosimetry.
PMID- 28517130
TI - SU-E-T-118: Characterization of EBT3 Films in Photon and Proton Beams.
AB - PURPOSE: To measure the calibration curves of EBT3 dosimetry films in photon and
proton beams and to quantify the related uncertainties from one beam type to
another. METHODS: EBT3 Gafchromic films have similar properties than EBT2 with a
symmetric construction and a matte polyester substrate to prevent Newton's ring
artefacts. Films from a same batch were exposed in three different beam
qualities, an Elekta SL25 6 MV photon beam, a 100 MeV 5*5cm2 proton beam
delivered by pencil-beam scanning dedicated system from IBA and a 60 MeV fixed
proton beam (2.5cm in diameter) at Clatterbridge Center for Oncology (CCO), UK.
The films were read using an EPSON 10000 XL/PRO scanner. Film calibration curves
were acquired for all modalities within a range of 0.05 to 20 Gy. Influence of
increasing linear-energy transfer (LET) on film response was investigated by
comparing dose measured by EBT3 to a silicon diode detector in depth for a fully
modulated beam using the CCO beam line (homogeneous dose with distal end at 3.1cm
in water). A comprehensive uncertainty budget (reproducibility, uniformity'|) was
estimated on films irradiated by Elekta SL25. RESULTS: The main source of
uncertainty was the non-uniformity of the scanner response. By placing all the
irradiated films at the center of the scanner, the uncertainty could be reduced
from 5.8% to 1.9% (1 sigma). For all beams and energies, the calibration curves
were matched within uncertainties. Along the fully-modulated depth dose curve,
diode and EBT3 measurement were in a 4% agreement point-to-point, indicating
films weak dependence with LET. CONCLUSIONS: The weak influence of LET, beam type
and energy on film response as well as its small uncertainty make EBT3 suitable
for relative dosimetry and a promising candidate for measuring correction factors
(quality, recombination,'|) for reference dosimetry with ion chambers of non
standard beams (e.g pencil-beam scanning proton-therapy). a?oeThis work is
supported by the Walloon Region under the project name InVivoIGT, convention
number 1017266.a?.
PMID- 28517131
TI - SU-E-T-90: Investigation of Different Bleaching Wavelengths on the Absorbed-Dose
Sensitivity of NanoDot OSLDs Exposed to 6 MV X-Ray Beams.
AB - PURPOSE: To determine the effect of different bleaching wavelengths on the
luminescence response of Al2 O3 :C optically stimulated luminescence detectors
(OSLDs) exposed to accumulated doses of 6 MV photon beams. METHODS: OSLDs of the
nanoDot type were used and readout with a microStar InLight reader. To determine
the effect of different bleaching wavelengths on the luminescence response of
nanoDot OSLDs, we optically reset (bleached) the OSLDs with 26 W fluorescent
lamps in two modes: (i) directly under the lamps for 10, 120 and 600 min; and
(ii) with a long pass filter for 55, 600 and 2400 min. The long pass filter
blocks wavelengths below 495 nm, hence the longer bleaching duration to attain
equivalent OSL signals as bleaching directly under the lamps. Changes in the
sensitivity of the nanoDot OSLDs were determined for an irradiation-readout
bleaching-readout cycle, after irradiations with 1 and 10 Gy dose fractions.
RESULTS: The nanoDot OSLDs presented a linear response to dose up to 2 Gy and
supra-linear response afterwards. They produced different OSL signal loss and
fading behaviors for doses of 1 and 10 Gy. OSLDs bleached for 120 min and 600 min
without and with the filter in 1 Gy fractions, did not exhibit any significant
change in sensitivity over an accumulated dose of 7 Gy. The OSLDs exposed with 10
Gy fractions exhibited a small under-response when bleached with filter, and an
over-response when bleached directly without filter. CONCLUSIONS: The nanoDot
OSLDs may be reused without a significant sensitivity change for accumulated
doses below 7 Gy. However, for accumulated doses beyond 10 Gy, nanoDot OSLDs show
significant sensitivity change and hence, need to be recalibrated for reuse. We
also concluded that the light spectrum used to reset the OSLDs has an influence
on the sensitivity of the detectors. Natural Sciences and Engineering Research
Council of Canada.
PMID- 28517132
TI - SU-E-T-129: Rescaling of IMRT Verification Deviations from Detector Arrays into
the Patient.
AB - PURPOSE: To discuss a method of "rescaling" failures detected in a Gamma-Index
analysis with detector arrays into the patient as a re-evaluation method in IMRT
verifications. METHODS: In a homogeneous phantom, plane signals measured with
ionisation chamber arrays during IMRT field-by-field verifications can be
understood as resulting from the convolution of the incident photon fluence with
two spatially invariant kernels (dose deposition in the measurement plane and
spatial detector response). In principle, Gamma-Index deviations between planned
and the measured plane signal profiles can therefore be "back-projected" into a
deviation of the photon fluence profile from the planned one which can be
"forward-projected" as a dose deviation at test points in the patient. Assuming
this model for each field under investigation, all Gamma-Index failures in a
certain array region can thus be "rescaled" as deviations of the patient dose and
evaluated by with patient related tolerances. The method is evaluated in the
prostate and H&N region by use of the 2D-ARRAY729 and VeriSoft5.0. The software
offers the possibility to project the position of the ionization chambers onto
the patient's CT. Thereby, the field specific analysis of deviations between
measurements and plan is supported by suitable imaging procedures. Simulated
Gamma-Index failures (3mm/3%) have been evaluated according to the method
described above and compared with direct dose calculations. RESULTS: The degree
of consistency between relative dose deviations predicted from 2D-ARRAY
evaluations and corresponding relative dose deviations calculated within the
patient is found to be in an acceptable range. The applicability in regions of
inhomogeneity boundaries (air-tissue) and out of field regions was not included
in this study and will be analyzed in the future. CONCLUSIONS: In combination
with the described visualization tools, the method offers the possibility to re
evaluate the dose deviations inside the patient when Gamma-Index failures have
been detected with 2D-arrays.
PMID- 28517133
TI - SU-E-T-100: How to Improve the Dose Accuracy for Gantry Angle Dependent Patient
Specific IMRT QA Using 2D Ion Chamber Array with Octavius Phantom.
AB - PURPOSE: To determine the cross calibration factors which can predict more
accurate dose distribution for fixed beam IMRT QA using Octavius phantom.
METHODS: The ion chamber based Octavius 2D-array detector (PTW, Freiburg,
Germany) is a step in the right direction to measure the absolute dose and dose
distribution for patient specific IMRT QA. However, the directional dependency of
this detector made it less than desirable for angle dependent IMRT QA. We
evaluated the new Octavius system (PTW, Freiburg, Germany) for angle dependent
IMRT QA which compensates the response due to directional dependency. The system
is designed for full arc VMAT QA, but does not always work for the discrete angle
IMRT QA due to non-averaging of errors caused by directional dependence of
detectors. The proposed method uses correction factors for each gantry angle. The
dose for a 10cm * 10cm open field for each gantry angle was calculated by
treatment planning system and measured using the Octavius phantom. The correction
factors were determined at each gantry angle and the dose distribution was
renormalized at each angle using correction factors. RESULTS: The discrepancy
between measured and planned dose per monitor unit depended on the gantry angle
and were in the range of +-4% using the PTW method. Using our method, uncertainty
due to the detector angle dependency was eliminated. CONCLUSIONS: The new method
removes the angle dependency of ion chamber based 2D array detector for the fixed
beam IMRT QA. It provides fast, accurate and more realistic results for angle
dependent IMRT QA.
PMID- 28517134
TI - SU-E-T-140: A Study of Gafchromic EBT-3 Film for the Dosimetry of X-Ray Beams.
AB - PURPOSE: To evaluate the dosimetric characteristics of the newly released
Gafchromic EBT3 film and determine its suitability for surface dose measurements
of 6MV x-ray beams. METHODS: Sheets of Gafchromic EBT3 film (Ashland Specialty
Ingredients, NJ, USA) were cut into rectangular samples according to the
providing user guide. All irradiations were performed using the 6MV x-ray beam on
a Novalis linear accelerator (Varian Medical Systems). Optical density (OD) -
dose calibration curves were determined by irradiating different film samples
with doses in the range from 0 to 3 Gy and were read out using an X-rite
densitometer using multiple readings over the samples surface. The OD was
measured at different times after irradiation in order to determine stability of
the film development. Surface doses were determined by placing film samples on
the surface of a Virtual Water phantom for a range of field sizes from 3*3 to
20*20 cm2 . RESULTS: Sheets of Gafchromic EBT3 film (Ashland Specialty
Ingredients, NJ, USA) were cut into rectangular samples according to the
providing user guide. All irradiations were performed using the 6MV x-ray beam on
a Novalis linear accelerator (Varian Medical Systems). Optical density (OD) -
dose calibration curves were determined by irradiating different film samples
with doses in the range from 0 to 3 Gy and were read out using an X-rite
densitometer using multiple readings over the samples surface. The OD was
measured at different times after irradiation in order to determine stability of
the film development. Surface doses were determined by placing film samples on
the surface of a Virtual Water phantom for a range of field sizes from 3*3 to
20*20 cm2 . CONCLUSIONS: The Gafchromic EBT-3 film has shown to be a stable and
useful dosimeter for megavoltage x-ray beams including the determination of
surface dose.
PMID- 28517136
TI - SU-E-T-143: Effect of Physical and Virtual Wedges on the Surface Dose at Various
SSD for 6 and 15 MV Photon Beam.
AB - PURPOSE: To study the effect of the virtual wedge and physical wedge filters on
the surface and build-up region doses for 6 and 15MV high-energy photon beams for
different field sizes and various source to surface distance(SSD). METHODS: The
measurements were made in water equivalent (PMMA) solid phantom in the build-up
region at various SSD for various field sizes using virtual and physical wedge
filters having different angles. A parallel-plate ion chamber (Markus) was used
to measure the percent depth doses at surface and buildup region. Plane parallel
ion chamber with fixed plate separation on the surface and buildup region would
perturbate the dose measured, to get the proper dose over response correction
factor was used. RESULTS: The percentage depth dose at surface (PDD0) increased
as the field size increased for open, virtual, and physical wedged beams. For
open, 30 degree physical, and virtual wedged beams, the surface doses were found
to be 15.4%, 11.2%, and 15.2% with 6-MV photons and 11.2%, 9.4%, 11.2% with 15-MV
photons, respectively, at 10 * 10 cm2 field size at 100cm SSD.As SSD increases
percentage depth dose at surface (PDD0) decreases for open,physical and virtual
wedge field. CONCLUSIONS: Percentage depth dose at surface (PDD0) of virtual
wedged beams were similar to those of open beams. PDD0 of physical wedged beams
were lower than those of open and virtual wedged beams. Surface doses for both PW
and VW increases with field size and small increase in surface dose for both PW
and VW fields as wedge angle increases especially for large fields.
PMID- 28517135
TI - SU-E-T-111: Single Line Multi-Detector Scintillation Dosimetry: Demonstration of
Feasibility.
AB - PURPOSE: Obtain feasibility data on the use of multiple scintillators on a single
optical line for dose measurements. METHODS: A CsI (Tl doped) crystal and a
plastic (Rexon Inc, Rp-408) scintillator detectors, both transparent, were
attached to the end of a fiberoptic line and connected to an Ocean Optics USB
2000 spectrometer. After baseline spectra, spectra with the two scintillators
adjacent to each other and then separated by a 7.6 cm plexiglass spacer were
obtained. Irradiations were performed using 6 MV X-ray beam from a Varian EX
linear accelerator. Utilizing the baseline spectra the dose received by each
scintillator were calculated from the measured spectral peaks of the linear
scintillator assemblies. Linearity tests were performed by varying dose and the
dose rate in a homogeneous radiation field covering both scintillators. Unequal
doses were delivered to the scintillator by gradually closing the collimator from
one direction, blocking one detector at a time. Doses to the scintillators were
modulated by different amount of solid water placed over the two detectors, as
well. RESULTS: Measured scintillation spectra agreed with the published spectra.
The spectra did not change with depth in the phantom. The multi-scintillator
system response was strictly linear between 1.67 and 40 MUs, (approx. 1.3 to 31
cGy) and dose rate independent between 100 to 600 MU/min. The profile curves
obtained by closing the collimator agreed with qualitatively expected curves.
Doses measured under different phantom thicknesses were in good agreement with
ion chamber measurements on the same locations (+/- 3%). The linearity and dose
rate independence allow absolute dose calibration for given beam energies and
scintillator arrangement. CONCLUSIONS: Multi-probe scintillation dosimetry along
a single optical fiber is possible in therapeutic irradiation conditions. This is
feasible by using signals from multiple select scintillators with distinct
spectroscopic responses arranged along an optical fiber.
PMID- 28517137
TI - SU-E-T-102: Evaluation of the Characteristics of TLD LiF:Mg.Ti-100 Powder: A
Measure of Consistency between Multiple Batches of Powder.
AB - PURPOSE: Analyze the characteristics of TLD LiF-100 powder between multiple LiF
crystal batches. METHODS: The RPC used TLD LiF-100 encapsulated powder to verify
the output for photon and electron beams for 4 to 23 MV X-ray beams and 6 to 23
MeV electron beams, respectively, from the past 15 years. During that time
period, the RPC commissioned more than 15 batches of TLD powder. Commissioning of
each batch of powder encompassed determining the system sensitivity (dose
response), linearity, energy and fading characteristics of each batch of powder
to determine the correction factors for the calculation of dose. The system
sensitivity is the signal/mg per unit known dose of 60Co for each reading
session. Other correction factors account for the loss of signal (fading) between
the irradiation and read dates, supralinearity of the dose response and energy
differences as compared to the 60Co irradiated standards. RESULTS: More than 15
batches of TLD were commissioned to determine correction factors for the
calculation of dose. The correction for fading, a characteristic of the LiF
crystal, varied by +/-1% between the multiple batches. The linearity correction,
between 25 and 600cGy, normalized to 300cGy, showed a maximum variation of +/-3%
between batches. The energy correction factors, as defined for the RPC beam
output audit system varied within +/-1.7% (one std dev.) for the 15 batches. The
system sensitivity is highly dependent on the LiF crystal grown for each batch,
specific TLD reader and reading session conditions. The system sensitivity, while
keeping the readers and reading sessions constant, varied by as much as 20%
between batches. CONCLUSIONS: Each batch of LiF-100 TLD powder showed variability
in their powder characteristics such that calculation of dose accurately, with
minimal uncertainty, requires a new commissioning. Work supported by PHS CA010953
awarded by NCI, DHHS.
PMID- 28517138
TI - SU-E-T-113: Volume Effect Correction Factor KV for Small-Field Photon Dosimetry
with Ionization Chambers.
AB - PURPOSE: The volume effect of ionization chambers gives rise to a spatial
averaging effect that can be expressed mathematically as the convolution of the
true dose profile with the detector's response function. The latter has been
shown to be best described by Gaussian distribution. Based on this knowledge, the
volume effect correction factor kV is derived. METHODS: To derive kV, a sixth
degree polynomial is fitted to the true dose profile: D(x) = a0 + a2*2 + a4*4 +
a6*6. The measured dose profile M(x) is calculated as the convolution product of
D(x) with a one-dimensional normalized Gauss function with standard deviation s.
Therefore kV at the dose maximum has the value D(0)/M(0), which is a function of
the coefficients a0,2,4,6 and the detector specific s. In the case where D(x) is
unknown, kV can be derived analogously from M(x) so that M(x) = b0 + b2*2 + b4*4
+ b6*6, where kV can now be expressed as a function of the coefficients b0,2,4,6
and s. RESULTS: The magnitudes of kV,lat and kV,long were calculated for 1 to 5
cm dose profiles using measured s values, both in the lateral and the
longitudinal directions, for a set of common ionization chambers. At field widths
above 2 cm, the values of kV,lat fall below 1.01 for all the chambers evaluated,
whereas it needs field widths above 4 cm to get all values of kV,long below 1.01.
Since the detector's signal is integrated over the sensitive volume, the total kV
can be calculated as kV,total = kV,lat . kV,long. CONCLUSIONS: In this work, a
correction is developed to eliminate the volume effect of ionization chambers
when they are positioned in the maxima of dose profiles, particularly for the
performance of output factor measurements for the calibration of narrow photon
beams.
PMID- 28517139
TI - SU-E-T-124: A Modified Winston Lutz Test Enabling Beam to Laser Angle
Measurements.
AB - PURPOSE: To present a modified Winston-Lutz-Test procedure able to measure beam
and laser angles. METHODS: Room lasers have not only to indicate the isocenter
spot but should also be aligned to the central beam axis. Therefore a modified WL
test, based on a cube phantom made of low density foam material was developed.
The classical steel sphere in the center is surrounded by 8 additional smaller
spheres located near the cube corners. Surface markers on the cube indicate the
position of the spheres and are used for easy setup to the lasers. Measurements
are made with a field size covering all spheres in the well known way, ideally
with a gantry mounted EPID. Result is an image of in total 9 spheres that is
influenced by the distances and incoming beam directions. An automated template
based detection algorithm then searches the image for the spheres as well as for
the outside field boundaries. Knowing the phantom geometry, it is now easy to
calculate the following parameters: Position of center sphere and laser to
central axis of the beam, beam angle to the orientation of the phantom and the
distance of the cube to the radiation source. Calculation result s then can be
used to correct the phantom position and orientation. A transfer device equipped
with a finder sight then allows to set the lasers. RESULTS: Test measurements
were taken at a Siemens Artiste. Here the detection accuracy for angles and
positions was tested. For smaller angles the automated detection works quite well
within an accuracy of around 0.1 degrees (max error 0.2 degrees ). Position
detection was below 1/10mm and showed clearly the effects of Gantry and
collimator sag. CONCLUSIONS: This method detects both, positions and angles of
laser and beam, enabling a higher precision laser setup.
PMID- 28517140
TI - SU-E-T-96: Energy Dependence of the New GafChromic- EBT3 Film's Dose Response
Curve.
AB - PURPOSE: To study and compare the dose response curves of the new GafChromic EBT3
film for megavoltage and kilovoltage x-ray beams, with different spatial
resolution. METHODS: Two sets of EBT3 films (lot#A101711-02) were exposed to each
x-ray beam (6MV, 15MV and 50kV) at 8 dose values (50-3200cGy). The megavoltage
beams were calibrated per AAPM TG-51 protocol while the kilovoltage beam was
calibrated following the TG-61 using an ionization chamber calibrated at NIST.
Each film piece was scanned three consecutive times in the center of Epson
10000XL flatbed scanner in transmission mode, landscape orientation, 48-bit color
at two separate spatial resolutions of 75 and 300 dpi. The data were analyzed
using ImageJ and, for each scanned image, a region of interest (ROI) of 2*2cm2 at
the field center was selected to obtain the mean pixel value with its standard
deviation in the ROI. For each energy, dose value and spatial resolution, the
average netOD and its associated uncertainty were determined. The Student's t
test was performed to evaluate the statistical differences between the netOD/dose
values of the three energy modalities, with different color channels and spatial
resolutions. RESULTS: The dose response curves for the three energy modalities
were compared in three color channels with 75 and 300dpi. Weak energy dependence
was found. For doses above 100cGy, no statistical differences were observed
between 6 and 15MV beams, regardless of spatial resolution. However, statistical
differences were observed between 50kV and the megavoltage beams. The degree of
energy dependence (from MV to 50kV) was found to be function of color channel,
dose level and spatial resolution. CONCLUSIONS: The dose response curves for
GafChromic EBT3 films were found to be weakly dependent on the energy of the
photon beams from 6MV to 50kV. The degree of energy dependence varies with color
channel, dose and spatial resolution. GafChromic EBT3 films were supplied by
Ashland Corp. This work was partially supported by DGAPA-UNAM grant IN102610 and
Conacyt Mexico grant 127409.
PMID- 28517141
TI - SU-E-T-135: Investigation of Commercial-Grade Flatbed Scanners and a Medical-
Grade Scanner for Radiochromic EBT Film Dosimetry.
AB - PURPOSE: To evaluate the characteristics of commercial-grade flatbed scanners and
medical-grade scanners for radiochromic EBT film dosimetry. METHODS: Performance
aspects of a Vidar Dosimetry Pro Advantage (Red), Epson 750 Pro, Microtek
ArtixScan 1800f, and Microtek ScanMaker 8700 scanner for EBT2 Gafchromic film
were evaluated in the categories of repeatability, maximum distinguishable
optical density (OD) differentiation, OD variance, and dose curve
characteristics. OD step film by Stouffer Industries containing 31 steps ranging
from 0.05 to 3.62 OD was used. EBT films were irradiated with dose ranging from
20 to 600 cGy in 6*6 cm2 field sizes and analyzed 24 hours later using RIT113 and
Tomotherapy Film Analyzer software. Scans were performed in transmissive mode,
landscape orientation, 16-bit image. The mean and standard deviation Analog to
Digital (A/D) scanner value was measured by selecting a 3*3 mm2 uniform area in
the central region of each OD step from a total of 20 scans performed over
several weeks. Repeatability was determined from the variance of OD step 0.38.
Maximum distinguishable OD was defined as the last OD step whose range of A/D
values does not overlap with its neighboring step. RESULTS: Repeatability
uncertainty ranged from 0.1% for Vidar to 4% for Epson. Average standard
deviation of OD steps ranged from 0.21% for Vidar to 6.4% for ArtixScan 1800f.
Maximum distinguishable optical density ranged from 3.38 for Vidar to 1.32 for
ScanMaker 8700. A/D range of each OD step corresponds to a dose range. Dose
ranges of OD steps varied from 1% for Vidar to 20% for ScanMaker 8700.
CONCLUSIONS: The Vidar exhibited a dose curve that utilized a broader range of OD
values than the other scanners. Vidar exhibited higher maximum distinguishable
OD, smaller variance in repeatability, smaller A/D value deviation per OD step,
and a shallower dose curve with respect to OD.
PMID- 28517142
TI - SU-E-T-106: Evaluation of Sensitivity and Uniformity of New Radiochromic Film
with Two Commercial Scanners.
AB - PURPOSE: A newly introduced radiochromic film, the GAFCHROMIC EBT3, has been
expected as much useful device for the IMRT dosimetry. The purpose of this study
was to investigate the sensitivity and the uniformity of the films between an
Epson ES-10000G flatbed scanner and a Vidar DosimetryPRO Advantage (Red) scanner.
METHODS: Doses ranging from 1 cGy to 1600 cGy with 15-MV photon beam was
irradiated to the film in a solid water phantom, respectively. All of the films
were then digitized after irradiation using both two scanners. Sensitivities,
local fluctuations of the film with two scanners were evaluated. Local
fluctuations were defined as the relative (percent) standard deviation of the
film response in ROIs (3 cmx3 cm). RESULTS: As to the Vidar scanner, the
sensitivity of the film was higher for low dose range (below <400 cGy). While, as
to the Epson scanner, the sensitivity using the red color channel was higher than
others for low dose range. At high dose range (above >400 cGy), the green color
channel had higher sensitivity than others. The Vidar scanner exhibited the lower
local fluctuations than the Epson scanner for all dose ranges. For the Epson
scanner, the red color channel had the lower local fluctuations than the green
and blue color channel for all dose ranges. CONCLUSIONS: This study shows the
characteristics of the new EBT3 films, in conjunction with the Epson ES-10000G
flatbed scanner and the Vidar DosimetryPRO Advantage (Red) scanner.
PMID- 28517143
TI - SU-E-T-117: A Point Densitometer Scanner for EBT2 Film Dosimetry.
AB - PURPOSE: To create and characterize a device that can accurately and reproducibly
digitize Gafchromic(R) EBT2 film for dosimetry. METHODS: We have constructed a
point densitometer scanner that allows the acquisition of 1 dimensional optical
density profiles of EBT2 dosimetry film at submillimeter resolution. An LED with
peak output at 636nm collimated and focused with an aspheric lens was used as a
light source. A large area photodiode was used as a detector. A custom
transimpedence amplifier was developed to optimize the detector signal response
for optical densities corresponding to a clinically relevant dose range (0 -
3Gy). A custom motorized translational stage was developed allowing 1 dimensional
scans and manual fine adjustment in the lateral direction. The entire scanner was
contained in a light tight enclosure to eliminate the effects of ambient light.
Dose profiles were generated from EBT2 films exposed uniformly to varying doses
using a superficial unit with the films placed on top of a solid water phantom.
Dose profiles were generated from the same films using a flatbed scanner (Epson
10000XL) implementing two and three optical channel corrections for film
inhomogeneity and the results were compared. RESULTS: Initial analysis of the
point densitometer shows a beam FWHM of 0.7mm and position error of the
translational stage at 0.02mm in the scan direction and 0.2mm in the lateral
direction. Reproducibility of the scans has been shown to within 1%. Orientation
dependence and measured dose homogeneity have been improved over corrected
flatbed digitization techniques. CONCLUSIONS: Preliminary characterization of the
point densitometer shows its potential as an improved quality assurance tool for
EBT2 film dosimetry.
PMID- 28517144
TI - SU-E-T-89: Characterization of Dental Restoration Material for Cs-137 Radiation
Dosimetry.
AB - PURPOSE: The purpose of this work is to characterize the radiation-induced
thermoluminescence properties of a dental restoration material and to see if the
material might be feasible for use in retrospective radiation dosimetry. METHODS:
Retrospective, or accidental, dosimetry is the study of using nearby materials to
measure radiation received by individuals. In this project we obtained samples of
Ivoclar Vivadent e.max CAD material, a glass-ceramic used for making dental
restorations such as full or partial crowns. The samples were machined into
square chips .32 cm * .32 cm * .089 cm and annealed in the same furnace used by
the dentist. The samples were exposed to a Cs-137 source using a PMMA source
holder and then read in a Harshaw 3500 TLD reader. The samples were read without
nitrogen gas flux using heating rates of 5 degrees C/s or 10 degrees C/s up to a
maximum temperature of 400 degrees Celsius. The glow curves were analyzed using
Systat PeakFIT peak-fitting software and Microsoft Excel spreadsheets. The
authors gratefully thank Dr. Aaron Imdieke and the staff of River City Dental,
St. Cloud, MN for the dental restoration materials and the use of their dental
furnace. RESULTS: A sample subjected to a radiation exposure of .04 C/kg exhibits
a glow curve with a prominent peak at approximately 140 degrees Celsius, which is
well-modeled by the first order glow curve deconvolution formula developed by
Kitis, Gomez-Ros, and Tuyn. The activation energy corresponding to this peak is
approximately 1 eV. The thermoluminescent signal fades with time after exposure.
CONCLUSIONS: Ivoclar Vivadent e.max CAD dental restoration material has the
potential to be used as a material for retrospective Cs-137 radiation dosimetry.
Future work could look at its thermoluminescent dosimetry properties in more
detail and also at other dental restoration materials. The authors would like to
thank Dr. Aaron Imdieke and the staff of River City Dental, St. Cloud, MN, for
the donation of scrap dental restoration materials and the use of their dental
furnace.
PMID- 28517145
TI - SU-E-T-128: Dosimetric Characteristics of Gafchromic EBT3 Films for Megavoltage
Photon and Proton Beams.
AB - PURPOSE: Gafchromic film for quantitative analysis was renewed from EBT2 to EBT3
film in November 2011. The purpose of this study is to investigate the relevant
characteristics of EBT3 film for its application in dosimetric verification for
IMRT/VMAT or proton therapy. METHOD: We investigated the characteristics of EBT3
film with comparison of previous EBT2 film. The experiments in this study
composed two categories. At first, the photo spectroscopy for the irradiated film
was compared between EBT2 and EBT3. The film 1 day after the irradiation was
analyzed by a photo spectrometer (SR520: JASCO Corporation, Japan). Secondly, we
investigated several calibration curves which obtained by same batch. The films
were calibrated by irradiation the films to 13 dose steps. The irradiated films
were scanned by a flatbed scanner (ES-10000XL, Epson-Seiko Corporation, Japan).
The difference on scan orientation was evaluated alternate portrait and landscape
directions. The photon and proton beams were delivered from Clinac 21EX (Varian)
and Mitsubishi machine, respectively. RESULTS: The peak absorption wavelength of
EBT3 film and its response at all active range were basically same with that of
EBT2 film. The peak wavelength of photo absorption in EBT3 was observed at 585
and 634 nm. The fog optical density was increased due to the hazy matte polyester
for active layer. However, there is no change the tendency of the calibration
curve responding to megavoltage photon and proton beams. The scan orientation
dependency of EBT3 film was observed with similar to EBT2 film. The optical
density of portrait orientation was 10% higher than that of landscape
orientation. CONCLUSION: The dosimetric characteristics of EBT3 film were
basically same with EBT2 film. With regard to the matte polyester, the creation
of Newton's rings during scanning procedure was reduced. However, the suitable
scan protocol should be used for accurate film dosimetry.
PMID- 28517146
TI - SU-E-T-99: Small Field Output Factor Measurement Using MAGIC Gel Dosimeter in 3T
MRI.
AB - PURPOSE: Small field dosimetry is very important because of radiation therapy
techniques that use small fields such as IMRT, gamma and body radiosurgery,
cyberknife and tomotherapy. We investigated use of a MAGIC (Methacrylic and
Ascorbic acid in Gelatin Initiated by Copper) gel dosimeter to quantitatively
measure small field output factors (OFs) for 6MV x rays. METHODS: In this work,
MAGIC (Gelatin 9%; Methacrylic acid 4%; CuSO4 0.1mM; Ascorbic ascid 2mM; Glucose
10%) gel phantoms were developed to measure the 6MV x-ray output factors for 1*1
up to 10*10 cm2 square fields (Varian 2100C linear accelerator). For comparison,
3 ion chambers (PTW:TN30013, Exradin A12, Capintec PR-05P), Gafchromic film
(EBT2), and TLD (LiF-100) were used to measure the small field OFs under
identical experimental conditions: 6cm depth (solid water), SAD=100cm, SSD =
94cm, 6MV, 512 MUs per irradiation. Relative OFs were normalized to a reference
field (10*10 cm2 @ SAD =100cm). MAGIC gel dosimeters were scanned in a 3T GE
signa(r) EXCITETM clinical scanner using a Spin Echo pulse sequence for dose
distribution readout (pixel size = 0.4mm, slice thickness 3mm, TR = 4000ms, TE =
10ms and 110ms, respectively). Gel dose distributions were then calculated using
custom Matlab code. RESULTS: 6MV x-ray OFs versus field size for all detectors
were graphically compared. The MAGIC polymer gel dosimeter OF for a 1*1 cm2 field
is 0.612 (+/- 5%), approximately 2% different from the OFs measured using small
volume dosimeters (TLD, EBT2 film and the Capintec PR-05P ion chamber). Larger
ion chamber (PTW:TN30013 and Exradin A12, both ~ 0.6cc) OFs were low (OF = 0.26
for 1*1cm2 ) due to nonequilibrium and partial volume conditions. CONCLUSIONS:
MAGIC gel dosimeter with 3T MRI scanner as a read-out makes it an ideal tool for
small field dosimetry.
PMID- 28517147
TI - SU-E-T-139: Feasibility Study of Glass Dosimeter for in Vivo Measurement:
Dosimetric Characterization and Clinical Application in Proton Beams.
AB - PURPOSE: To evaluate the suitability of the GD-301 glass dosimeter for use in in
vivo dose verification in proton therapy. METHODS: The glass dosimeter was
analyzed for its dosimetric characteristic in proton beam. Dosimeters were
calibrated in a water phantom using a stair-like holder specially designed for
this study. To determine the accuracy of the glass dosimeter in proton dose
measurements, we compared the glass dosimeter and TLD dose measurements of plan
delivery using a cylindrical phantom. We investigated the feasibility of the
glass dosimeter for the measurement of dose distributions near the superficial
region for proton therapy plans with a varying separation between the target
volume and the surface of 6 patients. RESULTS: Uniformity was within 1.5%. The
dose-response has a good linear. Dose-rate, fading, and energy dependence were
found to be within 3%. The beam profile measured using the glass dosimeter was in
good agreement with the profile obtained from the ionization chamber. Depth-dose
distributions in non-modulated and modulated proton beams obtained with the glass
dosimeter were estimated to be within 3%, which was lower than those with the
ionization chamber. In the phantom study, the difference of isocenter dose
between the delivery dose calculated by the Eclipse and that of the measured by
the glass dosimeter was within 5%. In vivo dosimetry of patients, given the
results of the glass dosimeter and TLD measurements, calculated doses on the
surface of the patient are typically overestimated between 4% and 16%.
CONCLUSIONS: As such, it is recommended that bolus be added for these clinical
cases. We also believe that the glass dosimeter has considerable potential to be
used for in vivo patient proton dosimetry.
PMID- 28517148
TI - SU-E-T-110: Small Electron Field Surface Dosimetry Using Solid State Detectors.
AB - PURPOSE: Solid state detectors from two independent systems have shown similar
over-responses to small electron fields used for treatment of surface lesions. We
propose to evaluate the accuracy of solid state detector systems for highly
blocked electron fields as a method for clinical dosimetry and determine the
cause for any deviations from expected dose-delivery calculations. METHODS: A QED
Diode detector system and a Best-Medical MOSFET dosimeter system were used to
measure relative output factors (ROF's) for a range of blocked electron fields
with 3 different electron energies. Measurements were taken on the surface of a
Solid-Water phantom as well as under varying thicknesses of bolus (surface to
dmax) to determine the extent of this effect with increasing depth. Measurements
were compared with expected results obtained during machine commissioning with an
A-14 micro-ionization chamber. RESULTS: Field sizes larger than 4*4 cm2 showed
little significant deviation from expected output factor values. However, fields
smaller than this threshold showed as much as a 30% over-response of the solid
state detectors compared to ion chamber measurements on the surface. This
deviation was consistent over multiple measurements using both systems. The
degree of over-response is both energy and effective field size dependent. As the
effective depth of measurement increases, the relative differences in responses
decrease and eventually converge. CONCLUSIONS: Surface dosimetry using solid
state detectors is a straightforward method of verifying dosimetric calculations.
Care must be taken when using these systems for surface dosimetry with highly
blocked fields as their non-tissue equivalence makes these detectors overly
sensitive to low-energy scattered electrons and bremsstrahlung photons produced
from the block edge. Measurements taken near dmax will not show a significant
deviation from the actual dose and do not need to account for this effect.
PMID- 28517149
TI - SU-E-T-121: Investigating the Optimal Scanning Resolution for Radiochromic EBT-2
Films Using an Epson 10000XL Flatbed Scanner.
AB - PURPOSE: The purpose of this work is to determine the optimal scanner resolution
of an Epson 10000XL scanner for the analysis of radiochromic EBT-2 films. Using
Fourier analysis and the Nyquist-Shanon sampling theory, the highest frequency
component required to sufficiently reproduce a previously measured step dose
profile was investigated. METHODS: A setup was created, in which one half of a
6*6cm2 EBT-2 film was shielded on exposure using a 15*5*10cm3 lead block to
obtain sharp step dose profiles. The film itself was placed between two 6cm RW3
stacks on top of which the lead block was placed. Using a Siemens Primus linear
accelerator operating at 6/15MV nominal energies, the setup was exposed to 400MUs
at 6MV and 500MUs at 15MV respectively. Preliminary investigations were performed
without RW3 between the lead and film. Initial image acquisition was performed at
600dpi to minimize information loss. Using the average of five line profiles, a
uniformity correction algorithm provided by the manufacturer was implemented
prior to the Fast Fourier Transform (FFT) operation. In an iterative process, all
frequency components above a cut-off frequency wcut were successively removed and
the original image reconstructed with the inverse FFT operation. The goodness of
fit was evaluated by comparing the change in penumbra width on image
reconstruction. RESULTS: The minimum scanning resolution required to analyze the
step dose profiles created without build-up material was 52dpi for 6MV and 30dpi
for 15MV. By adding build-up material, in the areas of secondary electron
equilibrium the required resolution reduces to 12dpi for 6MV and 8dpi for 15MV.
CONCLUSIONS: For sufficient image reproduction within any information loss,
resolutions as low as 52dpi at 6MV and 30dpi at 15MV are sufficient for
evaluating EBT-2 films. This is in compliance with 50dpi recommended by the
manufacturer.
PMID- 28517150
TI - SU-E-T-142: Evaluation of the Energy Dependence of Gafchromic EBT3 Film for
Electron Beams.
AB - PURPOSE: To evaluate the energy dependence of Gafchromic EBT3 film for
establishing a quality assurance method of bolus electron conformal radiotherapy.
METHODS: We irradiated electron beam to EBT3 films, which were set in the water
tank. The linear accelerator used was Varian Clinac 21EX. The energy of electron
beams were 9 and 12 MeV. The irradiated field size was 10*10 cm2 and the source
to surface distance was 100 cm. The depths of measurement were 22 (depth of dose
maximum; dmax), 31, and 37 mm for 9 MeV and 28 (dmax), 43, and 50 mm for 12 MeV.
The irradiated doses were 25, 50, 75, 100, 150, 200, and 300 cGy. EBT3 films were
readout with a flat-bed scanner 48 hours after irradiation, and the optical
density (OD) curve was obtained for each beam energy and depth. The OD curves
were approximated by a third-order polynomial. The doses were evaluated at netOD
0.1 and 0.3 from the approximated curves. RESULTS: The differences of the
evaluated doses from those for 9 MeV at 22 mm depth were from 2 to 14 % for
netOD=0.1, and from 1 to 13 % for netOD=0.3, respectively. The netOD curves of
dmax for both energies showed good agreement, while large discrepancy was found
in the deeper depths. CONCLUSIONS: The dependence of dose response of EBT3 film
on electron beam energy was small at dmax, while it increased at deeper depth in
the present study. It can be considered that the discrepancy was caused by setup
error because dose gradient was steeper at the deeper region. In future work, we
will perform more precise measurement with a solid phantom to evaluate the energy
dependence of EBT3 film.
PMID- 28517151
TI - SU-E-T-112: Experimental Characterization of a Novel Thermal Reservoir for
Consistent and Accurate Annealing of High-Sensitivity TLDs.
AB - PURPOSE: To develop and characterize a novel thermal reservoir for consistent and
accurate annealing of high-sensitivity thermoluminescence dosimeters (TLD-100H)
for dosimetry of brachytherapy sources. METHODS: The sensitivity of TLD-100H is
about 18 times that of TLD-100 which has clear advantages in for interstitial
brachytherapy sources. However, the TLD-100H requires a short high temperature
annealing cycle (15 min.) and opening and closing the oven door causes
significant temperature fluctuations leading to unreliable measurements. A new
thermal reservoir made of aluminum alloy was developed to provide stable
temperature environment in a standard hot air oven. The thermal reservoir
consisted of a 20 cm * 20 cm * 8 cm Al block with a machine-milled chamber in the
middle to house the aluminum TLD holding tray. The thermal reservoir was placed
inside the oven until it reaches thermal equilibrium with oven chamber. The
temperatures of the oven chamber, heat reservoir, and TLD holding tray were
monitored by two independent thermo-couples which interfaced digitally to a
control computer. A LabView interface was written for monitoring and recording
the temperatures in TLD holding tray, the thermal reservoir, and oven chamber.
The temperature profiles were measured as a function of oven-door open duration.
The settings for oven chamber temperature and oven door open-close duration were
optimized to achieve a stable temperature of 240 0C in the TLD holding tray.
Complete temperature profiles of the TLD annealing tray over the entire annealing
process were obtained. RESULTS: A LabView interface was written for monitoring
and recording the temperatures in TLD holding The use of the thermal reservoir
has significantly reduced the temperature fluctuations caused by the opening of
oven door when inserting the TLD holding tray into the oven chamber. It has
enabled consistent annealing of high-sensitivity TLDs. CONCLUSIONS: A
comprehensive characterization of a custom-built novel thermal reservoir for
annealing high-sensitivity TLD has been carried out. It enabled consistent and
accurate annealing of high- sensitivity TLDs which could significantly improve
the efficiency of brachytherapy source characterizations. Supported in part by
NIH grant R01-CA134627.
PMID- 28517152
TI - SU-E-T-123: Understanding the Meaning of IMRT QA Passing Rates with a 2D Diode
Array.
AB - PURPOSE: A lower than ideal tolerance limit is used in intensity-modulated
radiation therapy quality assurance (IMRT QA) with a 2D diode array due to
passing rate fluctuations. The objective is to identify patterns in the passing
rates to predict sources of uncertainty that can affect treatment delivery, for
example, the need to re-calibrate the multileaf collimator when the passing rates
start to decrease. METHODS: Five complex clinical prostate IMRT plans were
evaluated with a 2D diode array. The QA for each plan was repeated five times
during one and a half month period. One of the plans was randomly selected and
repeated the same day five consecutive times. The planar doses calculated by the
treatment planning system were compared to the measurements of the 2D diode
array. The individual passing rates per beam per plan were compared. RESULTS: The
average passing rate for each plan ranged from 94% to 97%. While the average
percent difference of this ranged between -7.67% to 17.61%. Additionally, the
minimum and maximum standard deviation among all beams was 0.13% and 9.63%
respectively. We also compared the standard deviation of a plan QA repeated
during different days versus a plan QA repeated during the same day. For the
former the highest standard deviation was 6.05 % while for the later 0.21%. We
noticed that the largest discrepancy between the passing rates was for angles at
around 155 degrees and 205 degrees . CONCLUSION: These results show some
inconsistency in the IMRT QA passing rates from one day to the next. Moreover,
lower passing rates for a specific angle like the ones shown here can represent
possible mechanical or tuning problems with the linear accelerator at these
specific locations. Early identification of these sources of uncertainty can
greatly improve the precision of the treatment delivery.
PMID- 28517153
TI - SU-E-T-95: Investigation of 3D Dosimetry for an Anthropomorphic Spine Phantom.
AB - PURPOSE: To evaluate 3D dosimetry for a spinal cord treatment plan delivery using
the Radiological Physics Center's (RPC) anthropomorphic spine phantom. METHODS:
The RPC's spine phantom currently uses radiochromic film and thermoluminescent
dosimeters (TLD) to evaluate spinal metastases treatments. A second dosimetry
insert for the phantom was created to hold a PRESAGE(r) 3D dosimeter which
matched the location of the TLD and film in the original insert. The phantom was
CT imaged with each insert and an IMRT treatment plan was developed. The IMRT
plan was delivered to the phantom twice; once with each insert. The film and
PRESAGE(r) were scanned on a CCD microdensitometer and optical-CT system,
reconstructed to a 2 mm slice width, respectively. The measured dose
distributions were compared to the treatment plan calculated dose distribution
using RPC in-house developed software or the Computational Environment for
Radiotherapy Research (CERR). Film and PRESAGE(r) dose profiles were taken across
several planes and compared for agreement. The distance to agreement (DTA)
between the measured data and treatment plan, within the high dose gradient
region, was quantified. RESULTS: The PRESAGE(r) and plan dose profiles agreed to
within 2and 1 mm in the AP and SI directions, respectively. The film and plan
also agreed to within 2 mm across all profiles. CONCLUSIONS: The PRESAGE(r) 3D
dosimeter, based on these preliminary data, shows potential as a dosimeter for
the RPC's phantom irradiation studies. Future work will add markers to the
PRESAGE(r) insert to allow for a reproducible registration in CERR and a an
optical-CT system, reconstructed to a 2 mm slice width dose calibration protocol
will be created. CA 100835.
PMID- 28517154
TI - SU-E-T-134: Patient Specific Quality Assurance of RapidArc Pre Treatment Plans
Using Semiflex 0.125 Cc Ionization Chamber.
AB - PURPOSE: To evaluate the Patient specific pre-treatment quality assurance for
hundred RapidArc plans using semiflex (0.125cc) ionization chambers. METHODS:
Absolute point dose were measured for head and neck, thorax and abdomen cases
using semiflex (0.125 cc) ionization chamber. Verification plan was created for
each treatment plan in eclipse 8.6 treatment planning system with the semiflex
ionization chamber and the octavius phantom. Measurements were performed on a
Varian Clinac2100C/D linear accelerator equipped with a millennium 120 leaf
collimator. All the results were compared with the fluence measurements using 2D
Seven29 ion chamber array combined with octavius phantom. RESULTS: Positive
absolute mean dose variation of 0.56 % was observed with thorax cases with a
standard deviation (SD) of +/- 1.13 between the plans with a range of -1.78% to
2.70%. Negative percentage dose errors were found with head and neck and abdomen
cases, with a mean variation of -0.43 % (SD +/- 1.50), (range -3.25 % to 2.85 %)
and -0.35 % (SD +/- 1.48), (range -3.10 % to 2.65 %) for head and neck and
abdomen cases respectively. Relative dose measurements with 2D array agreed well
with the TPS calculate for all the cases. The maximum percentage value failed in
gamma analysis was found to be 4.95, 4.75, and 4.88 for head and neck, thorax,
and abdomen cases respectively. In all the cases analysed the percentage dose
points failed the gamma criteria was less than 5%. CONCLUSIONS: On the basis of
the studies performed it can be concluded that the semiflex ionization chamber
having a volume of 0.125cc can be used efficiently for measuring the pre
treatment quality assurance of RapidArc plans for all the sites. The results
provide an overall accuracy when compared to fluence measurement done using 2D
array seven29.
PMID- 28517155
TI - SU-E-T-105: The LET Dependence of Liquid Ionization Chambers (LICs) in High-LET
Beams.
AB - PURPOSE: LICs are novel detectors for radiotherapy: the higher density of the
medium allows to build them with a smaller sensitive volume, making them
appealing in particle therapy. With RBE varying along the depth dose curve (DDC)
and with the rising interest in dose/LET-painting, verifying the LET is becoming
more important. Nevertheless, while the LET distributions for different ionizing
particles have been calculated, they have never been directly measured in
realistic therapeutic beams. Our interest in LICs is based on the
characterization of the beam quality in terms of LET. It has been shown in
earlier works that the extrapolation of the linear portion of the voltage curve
yields an intercept with the x-axis that depends on LET. The quantitative
establishment of this method, however, depends on how accurately recombination
effects are taken into account. METHODS: Due to the higher density of charge
carriers produced in the liquid, LICs have high recombination effects: general
recombination effects, involving pairs belonging to different tracks (dose rate
dependent), and initial recombination between ion-electron pairs belonging to the
same incident particle event (LET dependent). To perform this study we propose a
two-dimensional array of LICs, composed by a 16*8 matrix of 2*2 mm2 pixels, which
gives a fine spatial resolution on the plane. RESULTS: Voltage curves have been
measured for proton, carbon and oxygen beams available at the HIT facility in
Heidelberg for different energies and dose rates. After correcting the curves for
general recombination losses using the Three Voltage Method, we have indications
of dose rate independence, indicating successful correction. CONCLUSIONS: Further
investigations are foreseen to quantify the LET dependence along the DDC, where
different LET values are expected. A comparison with simulated dose averaged LET
values will give quantitative information about 2D LET distributions for
different beam species.
PMID- 28517156
TI - SU-E-T-116: The Water Equivalence of Organic Liquid Scintillators for Proton
Dosimetry.
AB - PURPOSE: Organic liquid scintillators are currently under investigation for use
in proton dosimetry. The purpose of this work is to evaluate the water
equivalence of these materials as a preliminary step to identify scintillators
that are well-suited to this purpose. METHODS: Stopping powers were calculated
for 0.001-1000 MeV protons in water, polystyrene, and two organic liquid
scintillators: BC-531 and OptiPhase 'Hi-Safe' 3 at 0%, 25%, and 50%
concentrations of water. Angular scatter was quantified by theta0, a
characteristic multiple Coulomb scattering angle analogous to the standard
deviation of a Gaussian distribution of proton angles relative to the incident
beam axis. Theta0 was calculated as a function of depth over the range of 200 MeV
protons in these materials. RESULTS: Collisional stopping power in BC-531 ranged
from +44% to +1% ofthat in water. It remained within 6% from 2-600 MeV. OptiPhase
ranged from +24% to -2%, with smaller deviations at increased water
concentrations. At all concentrations, OptiPhase showed smaller deviations than
polystyrene and BC-531 and remained within 1% of water from 2-600 MeV.Theta0 was
very similar for all materials, with deviations from water of 5 milliradians or
less over the majority of the proton range. BC-531 showed deviations of 10
milliradians or more in the last few millimeters of the range. OptiPhase showed
smaller deviations than BC-531 or polystyrene, and these deviations decreased
with increasing water concentration. CONCLUSIONS: OptiPhase was found to be more
water equivalent than BC-531 or polystyrene in stopping power and angular
scatter, and increased water concentration improved both quantities. Large
deviations in stopping power were only found below 2 MeV for any material, where
proton range is less than 0.1 millimeter. The deviations from water found in
angular scatter were less significant, and probably too small to affect
measurement.
PMID- 28517157
TI - SU-E-T-88: Evaluating Gantry Sag on Linear Accelerators and Introducing an MLC
Based Compensation Strategy.
AB - PURPOSE: Gantry sag is one of the well-known sources of mechanical imperfections
that compromise the spatial accuracy of radiation dose delivery. This study aims
to quantify the gantry sag on multiple linacs and to investigate a multiple leaf
collimator (MLC)-base strategy to compensate for gantry sag. METHODS: We used the
Winston-Lutz method to measure the gantry sag on three Varian linacs. A ball
bearing phantom was imaged with a square radiation field during gantry rotation.
The images were analyzed to derive the radiation isocenter and subsequently the
gantry sag, that is, the superior-inferior wobble of the radiation field center
from the radiation isocenter as a function of gantry angle. Compensation for
gantry sag was attempted by offsetting the MLC leaves at 90-degree collimator
angle. The amount of offset was the opposite of measured gantry sag, which was
gantry angle-specific. RESULTS: Gantry sag was reproducible within a six-month
period. On the three linacs, the maximum gantry sag was found to vary from 0.7 mm
to 1.0 mm, depending on the linac and the collimator angle. The radiation field
center moved inferiorly, or away from the gantry, when the gantry was rotated
from 0 to 180 degrees. Comparison of gantry sag at 0- and 90-degree collimator
angles showed that the uncertainty in MLC leaf positions did not increase the
gantry sag. Instead, gantry sag was caused primarily by nonideal gantry rotation.
After the MLC compensation was applied, the maximum gantry sag was reduced to
less than 0.2 mm. CONCLUSIONS: The results indicated that gantry sag on a linac
can be quantitatively measured with sub-millimeter precision, using a simple ball
bearing phantom and the electronic portal imaging device. Reduction of gantry sag
is feasible by applying a gantry angle-specific correction to MLC leaf positions
at 90 degree collimator angle.
PMID- 28517158
TI - SU-E-T-127: Feasibility Study for Using a 2D Array Detector for All Beam
Measurements in Monthly Quality Assurance Procedure for a Uniform Scanning Proton
Therapy System.
AB - PURPOSE: To develop a more efficient monthly quality assurance (QA) process by
utilizing one detector with multiple setups instead of multiple detectors with
multiple setups. METHOD: The Sun Nuclear IC Profiler was used to measure machine
output, transverse profiles, and depth-dose profiles. The IC Profiler contains
251 ionization chambers aligned in the X, Y, and diagonal axes, and was designed
to measure machine output and transverse profiles. In order to measure depth
doses, a Lucite compensator with an angled surface was fabricated. To test the
capability of the detector, a proton beam of 10.5 cm range in water was used. The
distal edge coincided with the overall water equivalent depth upstream of the
detector on central axis. The measurement was repeated with an additional 1.0 mm
of solid water placed in front of the detector. The measured profiles from both
measurements were compared to quantify the IC Profiler response for a small range
change. RESULTS: The IC Profiler performs within vendor specification for
measuring machine output and transverse profiles. When measuring depth-doses with
an angled compensator, the IC profiler measures a change in profile along central
axis of 17.0% for a 1.0mm range change. Based on overall reproducibility of the
beam delivery system, the IC profiler is capable of detecting 0.3 mm range shift.
Therefore, the sensivity of the IC profiler response is suffficient to detect sub
millimeter changes in delivered range. CONCLUSION: The Sun Nuclear IC Profiler is
capable of measuring machine output, transverse profiles, and depth-dose profile
constancy with a high degree of accuracy and precision. Using a single detector
for all beam measurements increases the overall QA efficiency by reducing
multiple detector overhead while not sacrificing the accuracy and precision of
the measurements.
PMID- 28517159
TI - SU-E-T-138: Quantification of Dwell Position Inaccuracy in Varian GammaMed HDR
Titanium Ring Applicators.
AB - PURPOSE: To quantify the dwell position inaccuracy in Titanium ring applicators
and develop a test to be performed quarterly, after source exchange. METHODS: All
three rings from our Titanium kit (30, 45, 60 deg.) were used for this study.
EDR2 film was placed on the Simulator table and a ring was taped to the film,
with a solid water slab as buildup. A 1-cm spacing dummy wire was inserted into
the ring. The film was exposed using 135 kV, 80 mA, 400 mAs. An HDR treatment was
then delivered using the even source dwell positions from 2 to 16, with a 5 mm
step size, nominal dwell time 0.4 sec/position. The procedure was repeated three
times for each ring. The films were scanned and analyzed with the RIT software.
The distance between the center of each source position to the adjacent dummy
dots was measured for each ring on all three films. An average shift (AS) was
obtained for each ring.New films were exposed with a treatment offset equal and
in the opposite direction relative to the AS for the ring used. The films were
visually inspected to assess if the source positions are centered in between two
adjacent dummy dots, and also scanned and analyzed with the RIT software. This
test will be performed quarterly to verify if the shifts remain stable. RESULTS:
The average shift was 2.5, 2.4, and 2.4 mm distally for the 30, 45, and 60 deg.
rings, respectively. The offset for the quarterly test was set to 2 mm
proximally, to take into account the 1 mm tolerance for the source position.
CONCLUSIONS: The dwell position inaccuracy in Titanium ring applicators was
quantified and the quarterly test was successfully performed for two quarters.
Work is started to assess the dosimetric implications of this shift.
PMID- 28517160
TI - SU-E-T-109: An Evaluation of a Newly Available Portal Dosimetry QA Tool for SRS
Dynamic Arc and VMAT.
AB - PURPOSE: In our institute, the MatriXX has been used for IMRT, VMAT and dynamic
arc QA. However, the small fields (<3cm) shaped by HDMLC for SRS dynamic arc (DA)
present QA measurement issues when using the MatriXX due to its limited
resolution (7.6 mm). A recently available portal dosimetry (PD) software tool in
Eclipse Version 10 is capable of performing QA for arc plans. This study is to
evaluate this new tool for QA. METHODS: EPID calibration was performed using a
Varian Novalis TX unit with HDMLCs for a 6X high dose rate SRS beam. The PDIP
algorithm was configured using measured beam data. Brainlab iPlan was used to
generate the DA patient treatment plans. The plans were then exported to Aria via
DICOM RT. A verification plan was created in Eclipse and the predicted portal
dose calculated. The comparison was done between predicted and measured portal
dose distributions. RESULTS: Compared with chamber array analysis, the measured
portal dose shows significant improvement in correlation with predicted dose. To
eliminate the uncertainty of dose normalization, absolute CU is chosen for
analysis. Gamma factor was studied. Thecriterion was set at 3%/1mm using a 10%
dose threshold such that 95% of the pixels had a gamma <1. QA was performed on 9
plans and the average gamma passing rate is 98.5%, with passing rates ranging
from 95% to 100%. CONCLUSIONS: With approximately 0.7mm resolution, it is shown
that the newly available PD tool is capable of overcoming the limitations of
chamber arrays for small field SRS QA and is also suitable for HDMLC QA to
provide detailed dose comparison with highly modulated dose profiles within a
small treatment field. In addition, the time needed to perform the QA procedure
using the PD tool is significantly shortened compared to the MatriXX.
PMID- 28517161
TI - SU-E-T-120: Minimum Absorbed Dose Limit for Gafchromic EBT2 Film Response after
Exposure to Low-Energy Photons.
AB - PURPOSE: To investigate the accuracy of the absorbed dose measured with
Gafchromic EBT2 film in low-energy photon radiation fieldsMethods: Six EBT2 film
(lot # F06110901) pieces (1cm2 ) per dose were exposed to x-rays of 50 kV, 80 kV,
120 kV and 60Co gamma rays from a Leksell Gamma Knife at dose values from 50 mGy
to 100 Gy. The x-ray beams were calibrated following the AAPMTG-61 protocol using
ionization chambers calibrated at NIST or Wisconsin University depending on the
beam quality, while the 60Co gamma was calibrated in water using MD-V2-55 film.
Each film piece was scanned once using a HP Scanjet 7650 document flatbed scanner
in transmission mode, 48-bit color at 300 dpi spatial-resolution. The data
analysis was made through the ImageJ. The measured light intensity for the red
channel with its associate standard deviation was used to evaluate the netOD and
its standard combined uncertainty. The absorbed dose as a function of the netOD
was fitted using the logistic model and the relative combined uncertainties were
evaluated for each energy photon beam. RESULTS: EBT2 film response curve depends
on the low-energy photons and the degree of energy-dependence is a function of
absorbed dose. The absorbed dose relative combined uncertainty as a function of
the absorbed dose indicates that the minimum absorbed dose limit is also energy
dependent. Lower is the energy photon; more accurate is the measurement at low
dose value. This can be explain by the fact that comparing to high energy
photons, low energy photons can produce locally enough ionization density to
create more color centre in the same film area. CONCLUSIONS: Minimum absorbed
dose limit of Gafchromic EBT2 films were found to be energy dependent. The
response curve depends on the low-energy photons and the degree of energy
dependence is a function of absorbed dose This work is partially supported by
DGAPA-UNAM grant IN102610 and Conacyt Mexico grant 127409.
PMID- 28517162
TI - SU-E-T-92: on the Use of High-Sensitivity Thermoluminescent Dosimeters (TLDs) for
Dosimetric Characterization of Low-Energy Brachytherapy Sources.
AB - PURPOSE: To investigate the utility and accuracy of high-sensitivity TLD for
dosimetric characterization of low-energy brachytherapy sources. METHODS: One
hundred high-sensitivity (TLD-100H) and 100 normal-sensitivity (TLD-100) TLDs
were used in this study. The TLD-100s were annealed at 400 degrees C for one hour
and then kept at room temperature for 45 minutes followed by 80 degrees C heating
for 24 hours. To prevent temperature overshot from reducing the sensitivity of
TLD-100Hs, a novel thermal reservoir was built, tested, and used to anneal TLD
100H at 240 0C for 15 minutes and then kept at room temperature for 45 minutes
followed by 100 0C heating for one hour. These TLDs were then irradiated
uniformly in a large cavity Cs-137 irradiator for biomedical research (Shepherd,
Mark III) to test their reproducibility and to establish their relative
sensitivities. The radial dose function of a Model AgX100 125I source was
measured using both types of TLDs in water-equivalent solid phantoms as a test
case. The radial dose function measured by the TLD-100H was compared with that
measured by TLD-100 to determine its utility in brachytherapy dosimetry
characterization. RESULTS: Consistent and accurate annealing of high-sensitivity
TLDs was achieved by using a custom-built thermal reservoir system. TLD-100H was
found to be about 18 times more sensitive than TLD-100. For a 125I source with a
source-strength of 2.7U, the irradiation time for radial dose function
characterization up to 7 cm can be cut down from 38 days to 3 days. The radial
dose function measured by TLD-100H agreed well (within +/-6%) with that measured
by TLD-100. CONCLUSIONS: A novel thermal reservoir was used for consistent
annealing of high-sensitivity TLDs. TLD-100H can significantly shorten the
irradiation time needed for a complete characterization of radial dose function.
Investigation of TLD-100H for complete brachytherapy source characterization is
in progress. Supported in part by NIH grant R01-CA134627.
PMID- 28517163
TI - SU-E-T-131: Influence of Scanning Speed on Measurements of Field Flatness and
Symmetry of Photon Beams.
AB - PURPOSE: The purpose of this study was to investigate influence of different
scanning speeds on measurements of photon beam flatness and symmetry. METHODS:
Commissioning and quality assurance of linear accelerators require extensive beam
measurements. To increase efficacy, we evaluated flatness, symmetry and penumbra
of 6MV photon beam using the Varian-TrueBeamTM system. Scanning speeds were 0.3,
0.5, 0.75, 1, 1.5, and 2.5cm/s. Measurements were performed in water phantom
(BluePhantom2 , IBA-Dosimetry) at depths of maximum dose, 5,10, and 20cm, for
10*10 cm field size. For each scanning speed and depth, measurements were
repeated five times to give results sufficient statistical significance, in both
crossline and inline directions. Beam flatness was calculated using variation
over mean (80%), whereas symmetry was calculated using point difference quotient
(IEC) algorithm. After filed scanning chamber (Wellhofer) was fully stopped,
system was paused for stabilization time of 15s to avoid buildup of ripples.
RESULTS: It was noticed for all measurements that minimum and maximum flatness
and symmetry were recorded when scanning speeds were 0.3cm and 2.5cm,
respectively. For depth of maximum dose, maximum flatness and symmetry were 0.82%
and 100.58% (crossplane), and 0.94% and 100.96% (inplane). The average was 0.76%
and 100.38% (SD 0.04 and 0.12) for crossplane; 0.89% and 100.87% (SD 0.04 and
0.06) for inplane measurements. As the scanning depth increased, flatness and
symmetry increased, but SD for all measurements was within the same range (0.04
0.07 and 0.04-0.12). The maximum absolute difference for flatness and symmetry
for maximum and minimum speed were 0.16% and 0.34%.However, for scanning speeds
from 0.5-1cm/s, results were almost identical with maximum SD 0.03 for both
flatness and symmetry. Use of different scanning speeds did not influence
penumbra; SD was 0 for all measurements. CONCLUSIONS: This study reveals small
influence of scanning speed within predefined range. Consequently, difference in
measurements does not have clinical significance.
PMID- 28517164
TI - SU-E-T-122: Dose Response Analysis of Radiochromic Films in Regions of Low Dose
Using Separation Color Components.
AB - PURPOSE: To evaluate the dose response of EBT2 films in regions of low dose using
the decomposition of the image's color channels (RGB, Red, Green and Blue).
METHODS: Doses ranging from 1 Gy to 60 Gy were used to calibrate the dose
response of Gafchromic (r) EBT2 films irradiated in 6MV photons beams. Segments
of film with dimensions of 8.5 cm * 8.5 cm were used. Another segment of film
with dimensions 8.5 cm * 20.25 cm was also irradiated with a maximum dose of 4Gy
to determine the percentage depth dose (PDD). The films were digitized by a
LaserJet M1132 MFP - HP (r) scanner in standard resolution of 150dpi and analyzed
by a routine created in MatLab to convert the image to gray levels as well as
assess the desired color components from the image. RESULTS: The green component
presented the higher sensitivity (17.8 a.u./Gy) when the separated color channels
and the shades of gray analysis are compared. The red component presented the
highest signal to noise ratio in the low dose range (63% at 1Gy). The blue
component presented low sensitivity (0.66 a.u./Gy) in the entire dose range. A
linear fitting (r=0.998) was used to the green and gray components until a dose
of 4 Gy. The red component presented a non-linear behavior in the entire dose
range. The useful dose range found was from 1 Gy to 15 Gy. The maximum
differences between the reference PDD, measured with ionization chamber in a
water phantom, and the PDDs determined with film were 6%, 9% and 14% for the
green, gray and red components, respectively. CONCLUSIONS: This work results show
that the use of radiochromic films on planning verification procedures in low
dose ranges can be benefit from the analysis of the image's separated color
components.
PMID- 28517165
TI - SU-E-T-94: Multileaf Collimator Performance and Validation of Quality Control
Tolerances.
AB - PURPOSE: The automated quality assurance system (AQUA) is a centralized quality
control (QC) software designed to automate QC tests. Statistical analysis of AQUA
results was performed to assess the geometric accuracy and long-term
reproducibility of a commercially available multileaf collimator (MLC) and
examine the applicability of the American Association of Physicists in Medicine
(AAPM) tolerances for MLC QC. METHODS: The MLC was first calibrated with AQUA by
minimizing leaf-positioning errors on megavoltage images for 5 different leaf
bank positions (-60 to 100 mm from radiation isocenter). Leaf-positioning
accuracy and reproducibility was assessed by repeating the AQUA test 5
times/week. The range of leaf-positioning error over leaf-bank positions and time
was reported. Measured leaf-positioning errors were then separated into
systematic and random error components. The systematic error corresponds to the
variation (standard deviation) in mean positioning errors between leaves over
leaf-bank positions and time. The random error quantifies the leaf position
variations around its mean and is calculated as the root-mean-square of the
individual leaf position standard deviations. RESULTS: To date, 2 different MLCs
have been calibrated using AQUA and 9-18 datasets have been acquired to assess
performance. For the unit with the longest follow up, the range of leaf
positioning errors was -0.62 to 0.85 mm and 98% of the measured leaf positions
(n=7200) were within +/-0.5 mm of the nominal position. The systematic error was
the main error component (+/-0.15 to +/-0.2 mm) and was attributed to the
residual errors after calibration. The random error was +/-0.07 mm for both units
and demonstrated good leaf-positioning reproducibility and limited uncertainty of
the AQUA measurements. CONCLUSIONS: Preliminary results show that after MLC
calibration with AQUA, leaf-positioning errors on two different units are well
within the AAPM-recommended +/-1 mm tolerances. Additional MLC performance
improvement is possible if residual errors after calibration can be reduced
further as the MLC demonstrated high reproducibility. Funded in part by Elekta
Inc.
PMID- 28517166
TI - SU-E-T-133: Isocenter Measurements with the Winston-Lutz Test: Impact on
Treatment Planning.
AB - PURPOSE: To assure high accuracy in radiation delivery during linear accelerator
based stereotactic radiosurgery procedures, a Winston-Lutz test is typically
performed to measure the effective isocenter wander over the wide range of gantry
and couch angles employed. Ideally, this deviation is lower than 1-1.5 mm
depending on institutional tolerances. Automation of this test with portal
imaging allows a large amount of data to be taken and processed. This study
explores the effect of various collimation techniques on beam-center stability,
and addresses one technique of repositioning in response. METHODS: Winston-Lutz
shots were obtained using a Trilogy linear accelerator, BrainLab Winston-Lutz
pointer, and electronic portal imaging from a full range of gantry and couch
angles. The test was repeated using MLCs, a 10mm stereotactic cone from BrainLab,
and jaws for beam collimation. All images were processed using an in-house MATLAB
based program which calculates the distance between the tungsten ball and
aperture center with accuracy within ~0.1mm. Ideal shifts were calculated by
minimizing this variation from gantry rotation alone, and performed manually.
RESULTS: The in-plane gantry sag was found to be on the order of ~0.8mm,
independent of collimation technique or setup. The MLC carriage had a ~0.3mm
cross-plane displacement to the inferior from the cone center, negated by a 90
degree collimator rotation. The total gantry misalignment was greatest near
gantry 180 (~1.5mm), varying by collimation method. Optimizing to minimize gantry
error reduced errors to less than 0.7mm but increased the effect of couch
rotation. CONCLUSIONS: Isocenter evaluation is dependent on collimation method
used, and should be conducted with the same technique as delivery. It may be
useful to consider the varying delivery accuracy from different couch/gantry
angles during treatment planning. Repositioning methods after couch rotation may
affect ideal laser positions.
PMID- 28517167
TI - SU-E-T-104: Commissioning and Dosimetric Characteristics of TrueBeam System:
Composite Data of Three TrueBeam Machines.
AB - INTRODUCTION: A TrueBeam linear accelerator (TB-LINAC) is designed to deliver
standard flattened and flattening-filter-free (FFF) beams. In our institute,
three TB-LINAC units are installed. In this work, composite data of the three
units and multi-unit comparison are presented. METHODS: Each TB-LINAC can deliver
photon beams from 4MV to 15MV, electron beams from 6MeV to 22MeV, and 6MV-FFF and
10MV-FFF. Dosimetric characteristics are systematically measured for
commissioning including percent depth dose (PDD), beam profile, relative scatter
factor, dynamic leaf shift, output factor and MLC leakage. Critic considerations
of Pion of FFF photon beams and dosimetric penumbra are investigated. RESULTS:
All measured PDDs and profiles of photon and electron matched well across the
three machines. Beam data were quantitatively compared and combined through
average to yield composite beam data. The discrepancies among the machines were
quantified using standard deviation (SD). For example, the mean SD of the PDDs
among the three units is 0.12%, and the mean SD of the profiles is 0.40% for 10MV
FFF open fields. The variations of Pion of the chamber CC13 is 1.2+/-0.1% under
6MV-FFF and 2.0+/-0.5% from dmax to the 18cm-off-axis point at 35cm depth under
40*40cm2 . The measured relative output factors range from 0.866 to 1.141 with
the mean discrepancy of 0.06+/-0.04% among the three units. The measured wedge
factors range from 0.863 to 1.254 with the mean overall discrepancy of 0.04+/
0.04%. The mean MLC transmission and dynamic leaf shift were measured from 1.0%
to 1.5% and from 0.77mm to 0.96 mm from 4MV to 15MV. The mean penumbra of various
photon beams are measured from 5.88+/-0.09mm to 5.99+/-0.13mm from 4MV to 15MV at
10cm depth of 10*10 cm2 . CONCLUSIONS: Dosimetric data demonstrated that the
three units could and had been matched well. The systematically measured data
might be useful for future reference.
PMID- 28517169
TI - SU-E-T-87: The Effect of Bleaching Wavelengths on the Regeneration of the
Optically Stimulated Luminescence Signal of NanoDot Dosimeters Pre-Exposed to
High-Doses.
AB - PURPOSE: To investigate the effect of bleaching wavelengths on the regeneration
of optically stimulated luminescence (OSL) signals in Al2 O3 :C nanoDot
dosimeters pre-exposed to high doses. Regeneration is the increase in the OSL
signal during storage of a bleached nanoDot that was previously pre-exposed to a
high dose. This phenomenon affects the accuracy of a calibration protocol
proposed by Jursinic 2010 (Med. Phys. 37:102) in which pre-exposure of nanoDots
to a high-dose was used to minimize changes in the sensitivity of the detector as
a function of accumulated dose. METHODS: Al2 O3 :C OSLDs of the type nanoDot were
used throughout this study. Readout was performed using the microStar reader.
Bleaching of the OSLDs was performed with four 26 W fluorescent light bulbs in
two modes: (i) directly under the lamps; and (ii) with the aid of a long-pass
optical filter placed over the nanoDots, partially blocking wavelengths below 495
nm. Eighteen nanoDots were pre-exposed to 1 kGy dose. Then the pre-exposed
nanoDots were bleached in two sets of 9 to very low residual OSL signals using
bleaching modes (i) and (ii) for 12 h and 45 h, respectively. The nanoDots were
then stored in dark and readout after various time intervals to monitor the
regeneration of the OSL signal. RESULTS: We fitted the regeneration of the OSL
signal using a saturation function and obtained rise-time values of 563 h and 630
h, for bleaching modes (i) and (ii), respectively. At the saturation level, the
equivalent doses were about 1.18 Gy and 0.38 Gy for modes (i) and (ii),
respectively. CONCLUSIONS: The regeneration rates of nanoDot OSLDs pre-exposed to
high doses depend on the bleaching light wavelength used to reset the detectors.
A bleaching source that has a low component of wavelengths below 495 nm can
minimize the regeneration of the OSL signal. Natural Sciences and Engineering
Research Council of Canada.
PMID- 28517168
TI - SU-E-T-115: A Novel Cylindrical 3D Water Scanner for Beam Data Collection: II.
Dosimetric Characteristics.
AB - PURPOSE: To study the dosimetric characteristics of a commercial three
dimensional water scanner (3D SCANNER, Sun Nuclear Corp). The novel cylindrical
scanner uses a compact electrometer mounted on the side of the tank, eliminating
the need for chamber extension cables. The electrometer has a wide dynamic range,
requiring no gain adjustment as scanning conditions change, e.g., field size,
dose rate, wedge field, etc. METHODS: Measurements from the 3D SCANNER were
compared against those from another commercial scanner (Blue Phantom, IBA
Dosimetry). Comparable collection intervals and scanning speeds were used on both
systems. Profile and depth measurements were performed for open field beams (6
and 18 MV; 10-cm and 30-cm squared fields; depths of dmax, 10, and 30 cm) and
wedged fields (6 and 18 MV; 30-cm squared field; depth of 10 cm). Electron beam
profile and depth measurements were performed for a 20-cm squared applicator (6,
12, and 20 MeV; depth of dmax). The root mean square (RMS) values were determined
for each scanner's measurements. RESULTS: The measured field sizes were within
0.06 cm and 0.05 cm for photon and electron beams, respectively. The photon
D10/D20 ratios differed by < 0.4% and the electron I50 values were within 0.02
cm. The RMS of the profiles was approximately 0.1% for both the 3D SCANNER and
Blue Phantom measurements. Between the two scanners, all measurements agreed
within RMS, excluding the penumbra region. Two exceptions occurred: a 0.5%
difference was observed in the shoulder of the 12 MeV profiles, and a 0.8%
difference was observed in the 6 MeV depth measurements near the surface.
CONCLUSIONS: The quality of the scanned profile and depth measurements from the
3D SCANNER is comparable to that of another commercial scanner. Both scanning
systems have similar levels of scanning noise. This work was partially supported
by a research grant from Sun Nuclear Corp., Melbourne, FL.
PMID- 28517170
TI - SU-E-T-126: Non-Reference Condition Correction Factor KNR of Typical Radiation
Detectors for the Dosimetry of High-Energy Photons.
AB - PURPOSE: To correct for the deviations of the detector response when typical
radiation detectors are used under non-reference conditions, factor kNR was
calculated from the known energy dependence of the detector response at photon
energies from 10 keV upwards and from clinical photon spectra within a large
water phantom beneath a Siemens Primus 6/15 MV linac. A Farmer type ion chamber
(NE2571), two TLD detector types and two diodes were investigated. METHODS:
Factor kNR was obtained as the ratio of the weighted responses Yt of a given
detector t under reference conditions xref (axial distance r = 0 cm, depth d = 10
cm, field size 10 * 10 cm2 and SSD = 100 cm) and that under non-reference
conditions * (off-axis points and depths for various field sizes); kNR =
Yt(xref)/Yt(x). For small field (SF) dosimetry, we evaluated correction factor
kNRSF, which refers to small field reference conditions (4 * 4 cm2 field).
RESULTS: For all detectors investigated, the deviations of kNR from unity were
highest outside the field, due to prevailing low-energy scatter contributions.
For the Farmer chamber and EDP-10 diode, the kNR deviations did not exceed 2%,
but were up to 60% for the EDD-5 diode, while kNR values for LiF:Mg,Cu,P and
LiF:Mg,Ti deviated at most 15% and 5% respectively. kNR values appear as unique
functions of the mean photon energy at the point of interest. CONCLUSIONS: Air
filled ion chambers show only small kNR variations, while for non-water
equivalent detectors, kNR variations depend on the detector response at low
photon energy. kNR can be presented as a unique function of the mean photon
energy at the point of interest. A 4 * 4 cm2 reference field is recommended for
small fields, with correction factor kNRSF varying almost negligibly from kNR
except for unshielded Si diodes.
PMID- 28517171
TI - SU-E-T-98: Towards Cell Nucleus Microdosimetry: Construction of a Confocal Laser
Scanning Fluorescence Microscope to Readout Fluorescence Nuclear Track Detectors
(FNTDs).
AB - PURPOSE: To construct a custom confocal laser scanning microscope (CLSM) capable
of resolving individual proton tracks in the volume of an Al2 O3 :C,Mg
fluorescent nuclear track detector (FNTD). The spatial resolution of the FNTD
technique is at the sub-micrometer scale. Therefore the FNTD technique has the
potential to perform radiation measurements at the cell nucleus scale. METHODS:
The crystal volume of an FNTD contains defects which become fluorescent F2+
centers after trapping delta electrons from ionizing radiation. These centers
have an absorption band centered at 620 nm and an emission band in the near
infrared. Events of energy deposition in the crystal are read-out using a CLSM
with sub-micrometer spatial resolution. Excitation light from a 635 nm laser is
focused in the crystal volume by an objective lens. Fluorescence is collected
back through the same path, filtered through a dichroic mirror, and focused
through a small pinhole onto an avalanche photodiode. Lateral scanning of the
focal point is performed with a scanning mirror galvanometer, and axial scanning
is performed using a stepper-motor stage. Control of electronics and image
acquisition was performed using a custom built LabVIEW VI and further image
processing was done using Java. The system was used to scan FNTDs exposed to a 6
MV x-ray beam and an unexposed FNTD. RESULTS: Fluorescence images above the
unexposed background were obtained at scan depths ranging from 5 - 10 micrometer
below the crystal surface using a 100 micrometer pinhole size. CONCLUSIONS:
Further work needs to be done to increase the resolution and the signal to noise
ratio of the images so that energy deposition events may be identified more
easily. Natural Sciences and Engineering Research Council of Canada.
PMID- 28517172
TI - SU-E-T-137: The Response of TLD-100 in Mixed Fields of Photons and Electrons.
AB - PURPOSE: Thermoluminescent dosimeters are used routinely for dosimetric
measurements of photon and electron fields. However, no work has been published
characterizing TLDs for use in combined photon and electron fields. This work
investigates the response of TLD-100 (LiF:Mg,Ti) in mixed fields of photon and
electron beam qualities. METHODS: TLDs were irradiated in a 6 MV photon beam, 6
MeV electron beam, and a NIST traceable cobalt-60 beam. TLDs were also irradiated
in a mixed field of the electron and photon beams. All irradiations were
normalized to absorbed dose to water as defined in the AAPM TG-51 report. The
average response per dose (nC/Gy) for each linac beam quality was normalized to
the average response per dose of the TLDs irradiated by the cobalt-60
standard.Irradiations were performed in a water tank and a Virtual WaterTM
phantom. Two TLD dose calibration curves for determining absorbed dose to water
were generated using photon and electron field TLD response data. These
individual beam quality dose calibration curves were applied to the TLDs
irradiated in the mixed field. RESULTS: The TLD response in the mixed field was
less sensitive than the response in the photon field and more sensitive than the
response in the electron field. TLD determination of dose in the mixed field
using the dose calibration curve generated by TLDs irradiated by photons resulted
in an underestimation of the delivered dose, while the use of a dose calibration
curve generated using electrons resulted in an overestimation of the delivered
dose. CONCLUSIONS: The relative response of TLD-100 in mixed fields fell
consistently between the photon nd electron relative responses. When using TLD
100 in mixed fields, the user must account for this intermediate response to
avoid an over- or underestimation of the dose due to calibration in a single
photon or electron field.
PMID- 28517173
TI - Breast cancer awareness among Indonesian women at moderate-to-high risk.
AB - In this descriptive cross-sectional study, we examined awareness of breast cancer
among Indonesian women at moderate-to high-risk of developing breast cancer. Data
were obtained from 87 eligible participants using the Modified Breast Cancer
Awareness Measure. The International Breast Cancer Intervention Study model was
used to identify women at moderate-to-high risk of developing breast cancer. The
data were analyzed using descriptive statistics. The results showed that none of
the participants had knowledge of age-related risk (0%). Other domains that
indicated low awareness were knowledge of lifetime risk (31%), followed by
knowledge of risk factors, in particular the item regarding menstruation at an
early age (12.6%). These results indicated that increasing awareness of breast
cancer risks is highly needed, in particular among women at moderate-to-high risk
of developing breast cancer in Indonesia.
PMID- 28517174
TI - High-Pressure NiAs-Type Modification of FeN.
AB - The combination of laser-heated diamond anvil cells and synchrotron Mossbauer
source spectroscopy were used to investigate high-temperature high-pressure
chemical reactions of iron and iron nitride Fe2 N with nitrogen. At pressures
between 10 and 45 GPa, significant magnetic hyperfine splitting indicated
compound formation after annealing at 1300 K. Subsequent in situ X-ray
diffraction reveals a new modification of FeN with NiAs-type crystal structure,
as also rationalized by first-principles total-energy and chemical-bonding
studies.
PMID- 28517175
TI - Comparison of the Human A2A Adenosine Receptor Recognition by Adenosine and
Inosine: New Insight from Supervised Molecular Dynamics Simulations.
AB - Adenosine deaminase converts adenosine into inosine. In contrast to adenosine,
relatively little attention has been paid to the physiological roles of inosine.
Nevertheless, recent studies have demonstrated that inosine has neuroprotective,
cardioprotective, immunomodulatory, and antidepressive effects. Inosine was
recently shown to be a less potent agonist than adenosine at the A2A adenosine
receptor. To better depict the differences in the mechanisms of receptor
recognition between adenosine and inosine, we carried out supervised molecular
dynamics (SuMD) simulations, and the results are analyzed herein.
PMID- 28517176
TI - SU-E-T-399: Dosimetric and Geometric Evaluation of a Novel Stereotactic
Radiotherapy Device for Breast Cancer: The GammaPod.
AB - PURPOSE: A dedicated stereotactic irradiation device, the GammaPodTM, was
developed to treat early stage breast cancer. This study presents the first
description of the dosimetric and geometric characteristics from the prototype
unit. METHODS: The GammaPod stereotactic radiotherapy device is an assembly of a
hemi-spherical source carrier containing 36 Co-60 sources, a tungsten collimator,
a dynamically controlled treatment table and a breast immobilization cup embedded
with a stereotactic coordinate system. The source carrier and the variable-size
collimator rotate synchronously to form 36 non-coplanar, concentric arcs focused
at the isocenter. The treatment table enables motion in three dimensions
facilitating continuous dose painting in comparison to a sphere packing approach.
Geometric and dosimetric evaluations and a method for absorbed dose calibration
are provided. Dosimetric verifications of the dynamically delivered plans are
performed for eight patients in hypothetical pre-op, post-op and dose painting
treatment scenarios. RESULTS: Loaded with a cumulative activity of 4320 Ci, the
GammaPod unit delivers 5.31 Gy/min at the isocenter. Due to non-coplanar beam
arrangement and dynamic dose shaping features, the GammaPod delivers uniform
doses to the targets with excellent conformity. The spatial accuracy of the
device is less than 1 mm. Single shot profiles with the 25 mm collimator are
measured with radiochromic film and found to be in good agreement with respect to
the MC based calculations (congruence of FWHM less than 1 mm). Dosimetric
verifications corresponding to all treatment plans corresponding to three target
scenarios for each of the eight patients demonstrated Gamma index pass rates
greater than 97%. CONCLUSIONS: The first description of the dosimetric and
geometric evaluation of the GammaPod was performed. The observed level of
agreement between the treatment planning system calculations and dosimetric
measurements has confirmed that the system can deliver highly complex treatment
plans with remarkable geometric and dosimetric accuracy. C Yu and J Zhang have
commercial affiliations with Xcision Medical Systems.
PMID- 28517177
TI - SU-E-T-410: Spine Radiosurgery Imaging Guidance Using ExacTrac and CT on rails.
AB - PURPOSE: To evaluate the patient setup accuracy and effectiveness using ExacTrac
and CT_on_rails systems. METHODS: We used Brainlab's Exactrac system and
Varian/GE's CT_on_rails for spine radiosurgery patient setup. Once the patient
was setup using the ExacTrac and couch position was recorded, fiducially markers
were placed on stable surfaces based on the room laser to indicate the linac iso
for the CT images. CT images were acquired using the on-rail CT with the couch
rotated 180 degrees. The couch was returned to 0 degree position, and
verification X-ray images were taken and corrections were made by ExacTrac. The
treatment CT images were registered with the planning CT using the in-house CAT
software and it displays the correct couch position based on CT which can be
compared with ExacTrac setup. The corrected couch positions from CT registration
are compared to those from ExacTrac. The translational discrepancies needed to be
within 2 mm for confirmation. If a discrepancy was greater than 2 mm,
investigation or re-setup was required. The rotation deviations were also
evaluated by ExacTrac and confirmed by the treatment CT images. We would also re
setup patient if Exactrac detected more than 3 degree rotation, or treatment CT
images showed significant target rotation compared to planning CT. The use of the
CTonrails took little extra time, but make the overall evaluation process easier,
faster and with more confidence. RESULTS: for 171 treatment sessions using this
approach, the mean discrepancies between CTonrails and ExacTrac setup is: x=0.0+/
1.0 mm, y=-0. 1+/-0.9 mm, z=0.2+/-0.9 mm; for rotations, about 3% of the cases
required re-setup patient due to significant rotation displayed by the treatment
CT on the CAT system. CONCLUSIONS: The combined use of ExacTrac and CT_on_Rails
systems can improve the overall setup accuracy and increase the confidence in
setup for spine radiosurgery treatments.
PMID- 28517179
TI - SU-E-T-413: Dose Verification for Linac-Based SRS Commissioning and Patient
Specific QA.
AB - PURPOSE: Stereotactic Radiosurgery (SRS) program commissioning is currently
relied on Radiological Physics Center (RPC) Head Neck phantom with Thermo
Luminescent Dosimeters (TLDs) for dose verification. However, due to the limited
accessibility of RPC Head Neck phantom, ongoing QA or patient specific dose
verification is not performed in most clinics. In this study, we proposed an SRS
dose verification approach for both SRS commissioning and patient specific dose
verification with widely available clinical instruments. METHODS: SRS treatment
plans were imposed onto a 14cm thick conventional solid water phantom (30cm *
30cm), with a PTW micro-chamber in the middle. Treatment couch angles were
renormalized to 90 or 270 degrees for two reasons: 1) micro-chamber's axis was
parallel to gantry rotation axis during all the arc beam delivery, which
minimizes the angle dependence effect (axis tilt) of micro-chamber. 2) Any
collision between the cone and conventional solid water phantom would be avoided
and there would be minimum attenuation effect from the couch. The arc
verification plan was then recalculated and compared to the measured absolute
dose by PTW micro-chamber. An End-to-End test with a CyberKnife Head Neck phantom
and GAFChromic EBT2 film was utilized as secondary dose delivery verification.
RESULTS: Cones with all twelve different sizes in SRS commissioning were tested.
For the cone size from 10mm to 30mm, the micro-chamber measurements agreed with
the computer calculations within 3%. However, when the cone size was reduced to
5mm, micro-chamber measurement was 10% lower than planned dose, indicating
underdose effect for small cone size. Additional measurements with Cyberknife
head phantom confirmed the dose delivery accuracy was within 5%. CONCLUSIONS: A
simple SRS dose verification method which only requires micro-chamber and
conventional solid water phantom has been presented and verified. This approach
will be valuable for SRS commissioning and ongoing SRS QA.
PMID- 28517178
TI - SU-E-T-431: Investigation of BrachyVisionTM AcurosTM Using Varian Surface
Applicators.
AB - PURPOSE: Conical brachytherapy surface applicators with diameters ranging from 10
mm to 45 mm have been developed by Varian Medical Systems, Inc. These applicators
are designed to be used with the GammaMedplus iX and VariSource iX high-dose rate
Ir-192 afterloaders, allowing for conformal dose delivery for the treatment of
surface lesions. Treatment plans for these applicators are created in
BrachyVision Acuros. Few studies have been completed with Acuros in clinical
situations. The purpose of this work is to perform a comparison of the Acuros
calculated dose distributions with those calculated using Monte Carlo and
measured with various detectors. METHODS: Surface applicator treatment plans for
each source/applicator combination were created using Acuros and a virtual water
phantom. Simulations to characterize the dose distributions were completed using
MCNP5 based on specifications provided by the manufacturer. A collision kerma
tally was used to determine the dose distributions at the surface and at depth in
water. Experimental verification of the depth-dose and surface dose distributions
was completed using an ionization chamber, and TLDs and film, respectively.
Acuros-calculated depth-dose and isodose values were compared to the Monte Carlo
and experimental values. RESULTS: Assessment of the surface dose distributions
shows a peak at the center of the applicator with rapid fall off to the edges.
The TPS-calculatedpercentage depth-dose curves were within 3.7% of the MC and
5.8% of the measured for the 30 mm applicator and were within 4.4% of the MC and
measured for the 35 mm applicator. CONCLUSIONS: BrachyVision Acuros is capable of
calculating the depth-dose and surface dose distributions for the simple water
phantom case with surface applicators. Investigation of additional treatment
geometries and applicators is ongoing. Conflict ofInterest: Varian Medical
Systems, Inc. provided financial support, software, sources, and applicators.
Varian Medical Systems, Inc. provided financial support, software, sources, and
applicators.
PMID- 28517180
TI - SU-E-T-424: Inter-Fraction Variation of High Dose Regions of OARS in MR Image
Based Cervix Brachytherapy Using Rigid Registration.
AB - PURPOSE: To quantify the inter fraction variation of spatial location of high
dose regions of OARs in MR-image based cervix brachytherapy using rigid
registration algorithm. METHODS: Retrospective analysis of 27 previously treated
patients under EMBRACE multi-centric trial was evaluated. Each patient had two
applications, API and AP2 with Vienna applicator. As part of the protocol, all
patients underwent MR imaging for each application, followed by volume
delineation (Oncentra v3.3) treatment planning & optimization (Plato sunrise,
Nucletron), documentation of DVH parameters based on GEC-ESTRO recommendations.
The volume receiving the dose D2cc from the plan with which the patient was
treated was contoured in each of the image series for OARs rectum, bladder,
sigmoid and small bowel region. Both the image series were exported to Eclipse
planning system (v8.6.14, VMS) and were co-registered with applicator as the
reference using rigid registration Results: Out of 27 patients, the overlapping
D2cc volumes were found in 21, 20, 10 and 4 patients for rectum, bladder, sigmoid
and small bowel respectively between AP1 and AP2. The mean(SD) volume of overlap
of D2cc was 0.20(0.23), 0.17(0.20), 0.07(0.14), and 0.09(0.11) for rectum,
bladder, sigmoid and small bowel respectively. The overlap volume had a wide
range which is evident from its standard deviation. The mean(SD) difference of
the absolute volumes between AP1 and AP2 was 22(20), 5(6), and 11(11) for
bladder, rectum and sigmoid respectively. The uncertainties include the
calculation of small overlapping volumes of D2cc, co-registration and variation
between applications. CONCLUSIONS: The inter-fraction variation of spatial
location of high dose regions were more consistent in rectum and bladder and less
in sigmoid and much lesser in small bowel region.
PMID- 28517181
TI - SU-E-T-435: Automatic Monte Carlo Dose Calculations of Proton Treatment Plans.
AB - PURPOSE: Providing a user friendly automated Monte Carlo dose computation system
for proton treatments using passively scattered and intensity modulated proton
therapy plans, developed at the proton therapy facility of the M.D. Anderson
Cancer Center. METHODS: In house software was developed to automatically extract
patient CT images, as well as the setup geometry and proton beam parameters from
DICOM files, to create a Monte Carlo (MCNPX) model simulating the beam line
arrangements of the various beams used in any given proton treatment plan. A
graphical user interface provides an easy and intuitive workspace. A library of
phase space files provides source proton beams with the desired modulation width
and range in water. Energy deposition is scored in the voxelized CT volume,
converted to dose and compared to results of analytical dose computations.
RESULTS: Monte Carlo models of patient specific beam line equipment, such as the
brass collimator and the range compensator, as well as avoxelized model of the
patient, are automatically created and implemented into the model of the
simulated beam. Simulation of proton beams result in energy deposition
distributions in a volume of interest defined by the user during program start.
CONCLUSIONS: Current efforts focus on production ofthe phase space library and
final debugging of the program flow. It is expected that a prototype version of
the system will be functional in summer 2012.
PMID- 28517182
TI - SU-E-T-401: Evaluation of Initial Setup Accuracy and Intra-Fraction Motion for
Spine SBRT Using Stereotactic Body Frames.
AB - PURPOSE: Quantify initial setup accuracy and intra-fraction motion using
stereotactic body frames (SBF) for spine SBRT. METHODS: 10 patients (11 sites, 31
fractions) treated with spine SBRT using SBF immobilization were evaluated for
initial setup accuracy and intra-fraction motion. Either the commercial Elekta
SBF or an in-house developed SBF (BHS-SBF) were used. The BHS-SBF uses the same
setup/immobilization principle as the Elekta but with increased interior space
and couch indexing. Both frames include sidewalls to conform the vac-loc rigidly
to the patient's sides. All patients were setup using the Brainlab ExacTrac
system which includes IR and stereoscopic kV x-ray based positioning. Patients
were initially positioned in the frame using skin tattoos then shifted to
treatment isocenter based on IR markers affixed to the frame with known geometry
relative to isocenter. kV imaging was acquired and automatic 6-D bony fusion
performed. Resulting translations and rotations give the initial setup accuracy.
Calculated shifts and rotations were performed using a robotic couch and
verification imaging acquired. The imaging/fusion process was repeated multiple
times during treatment providing intra-fraction motion data. RESULTS: Mean
initial setup error in the VRT, LNG and LAT directions was 0.1+/-3.0 mm (0.1+/
0.6 deg), 0.5+/-5.2 mm (0.1+/-1.1 deg) and -0.3+/- 3.7 mm (0.4+/-0.8 deg)
respectively. Mean 3-D error magnitude was 6.6 mm with a 95% certainty of 11.2
mm. Mean intra-fraction shifts observed in the VRT, LNG and LAT directions were
0.1+/-0.4 mm, -0.1+/-0.4 mm and 0.1+/-0.3 mm respectively. Mean 3-D intra
fraction shift magnitude was 0.6 mm with a 95% certainty of 1.4 mm. No
significant difference was observed between the SBFs. CONCLUSIONS: Patient
positioning is not sufficiently reproducible with the evaluated SBF to allow non
image guided treatment. However, provided image guidance is used for patient
positioning, these frames provide excellent immobilization which is on par with
mask based cranial radiosurgery.
PMID- 28517183
TI - SU-E-T-417: Tomotherapy Isocentricity: Is it Good Enough for Stereotactic
Radiosurgery?
AB - PURPOSE: To evaluate the isocenter accuracy of radiation beam relative to the
Tomotherapy linear accelerator's mechanical axis using a simplified Winston Lutz
test, and to determine if Tomotherapy system is accurate for SRS applications.
METHODS: BrainLab Winston Lutz pointer was setup on the Tomotherapy couch to the
isocenter according to the green lasers. Four static plans were created to
deliver radiation with 1cm jaw opening, all MLC closed except the central two
leaves, and gantry at 0, 90, 180 and 270 degree, respectively. Gafchromic EBT
films were taped on a solid water slab and placed on opposite side of gantry at a
fixed distance for each plan. After the exposure, the films were scanned using
Vidar scanner along with a 1 cm scale drawn (Figure 1-A, 2-A). The images were
first processed by ImageJ, using Find Edges function to enhance the visibility of
the boundaries of the circles, from a metal ball in the pointer, and the
rectangles defined by two central leaves and the jaws (Figure 1-B, 2-B). Then two
diagonal lines were drawn on each rectangle, and a cross on each circle, with the
cross sections representing the centers of the rectangles and circles,
respectively (Figure 1-C, 2-C). RESULTS: The displacements of the centers of the
circles from the centers of the rectangles for the first setup (films were 11cm
from the isocenter) were 0.50, 0.707, 1.0 and 0.707 millimeters for each gantry
angle, respectively, with an average of 0.73mm. The displacements of second setup
(films were 25cm from the isocenter) were 0.54, 1.07, 0.87 and 0.54 millimeters,
with an average of 0.75mm. CONCLUSIONS: The preliminary data show that the
radiation isocenter agrees with mechanical isocenter well within one millimeter
tolerance required for SRS treatments, which indicated Tomotherapy system is
suitable for such applications.
PMID- 28517184
TI - SU-E-T-384: An Easy Use Anthropomorphic Phantom for Lung IMRT QA.
AB - PURPOSE: Even though lung IMRT plans are calculated based on patient CT with
heterogeneity correction, patient-specific validations are often performed by
using measurements in homogeneous solid media. In this study we developed
heterogeneous phantoms for measurement-based validation of lung IMRT. METHODS:
Three slabs from thorax region of anthropomorphic RANDO phantom and virtual water
(VW) slabs were used to construct two versions of heterogeneous phantom, "Hetero
1" and "Hetero-2". The RANDO slabs are 2.5 cm thick. A two-dimensional diode
array detector, MapCHECK and an ion chamber were used for measurements. "Hetero
1" consisted of three RANDO slabs placed horizontally on the MapCHECK plus a 3cm
VW on the top. Hetero-2 was constructed by inserting a 2 cm VW with a chamber
cavity on top of the first RANDO slab above the MapCHECK. Two lung-IMRT plans
were generated using Pinnacle TPS, including a plan for the RPC Lung-Phantom. The
point doses were compared with ion chamber measurements and planar dose were
compared with MapCHECK measurements. RESULTS: The MapCHECK measurements were
performed using "Hetero-1" on a beam-by-beam basis for the two IMRT plans.
Passing rates under 3%/3mm Gamma criteria of were from 93.5% to 98.5% for all
beams. Accumulative measurements were performed using "Hetero-2" and the passing
rates under same criteria for two IMRT plans were 96.9% and 96.3% respectively,
and 95.2% and 98.5% for measurements with 5cm lateral-IsoCenter-shift including
more lung material. The differences between Ion-chamber- measurements and TPS
calculations were 1.2% and 1.71% for two IMRT plans. In vivo results obtained
from RPC-report for two TLDs inside the PTV were 98% and 99% between measurements
and calculations. CONCLUSIONS: An easy-to-setup heterogonous phantom for Lung
IMRT QA can be constructed by adopting thorax region slabs of anthropomorphic
type phantoms. It can be implemented as a convenient and efficient tool for lung
IMRT QA in a routine clinic.
PMID- 28517185
TI - SU-E-T-428: Class Solution for Prostate High Dose Rate Brachytherapy with Inverse
Planning Simulated Annealing.
AB - PURPOSE: To develop and validate a class solution for inverse planning simulated
annealing (IPSA) with CT based prostate high dose rate brachytherapy (HDR).
METHODS: Between November 2008 and November 2011, our institution treated 40
prostate cancer patients with HDR in 7 Gy fractions followed by external beam
radiotherapy. The HDR treatments were planned with Nucletron Oncentra using
manual graphical optimization (GO). Plans were optimized to the following
clinical goals: = 95% of prostate volume received 7 Gy, < 1 cc of rectum received
5.6 Gy, < 0.1 cc of rectum received 6.3 Gy, and < 0.01 cc of urethra received
8.75 Gy. New plans were manually customized using IPSA (MC-IPSA) for each patient
to match prostate coverage by the prescription dose to within +/- 1% of the GO
plans while meeting the rectal and urethral dose constraints. An IPSA class
solution (CS-IPSA) was created from the mean MC-IPSA parameters. New plans were
developed for each of these 40 patients using only CS-IPSA with no further
optimization. Additionally, plans were created on an independent dataset of 30
different patients using only CS-IPSA with no further optimization. RESULTS:
Plans were optimized in about 30 minutes using GO, MC-IPSA took an average of
14.1 +/- 6.5 minutes, and CS-IPSA optimizationwas < 1 minute. There was no
significant difference (p > 0.05) among the optimization methods for all clinical
goals over the 40 CS-IPSA source patients. There was no significant difference (p
> 0.05) between the source and the independent datasets for all clinical goals
when using CS-IPSA with no further optimization. CONCLUSION: A prostate HDR IPSA
class solution was developed and validated on a source and an independent
dataset. The IPSA class solution yields plans comparable to custom manual IPSA
and graphical optimization while saving considerable time.
PMID- 28517186
TI - SU-E-T-394: Comparison of Planned Dose Distribution Vs. Delivered Dose
Distribution for Both IMRT and Proton Therapy Using Weekly Repeat 4DCT Data Sets.
AB - PURPOSE: To evaluate treatment deviations and the impact of treatment modality in
the presence of breathing motion and anatomical changes during the course of lung
cancer radiotherapy. METHODS: Two non-small cell lung cancer patients were
enrolled in a randomized clinical trial to compare IMRT and proton therapy. To
rigorously evaluate the impact of motion and anatomical changes, we used a '5D'
dose accumulation approach to sum dose distributions from phase-to-phase and week
to-week to the reference (end-expiration) phase of the original planning 4DCT
data set. Six to eight weekly 4DCT data sets that consisted of 10 breathing
phases were acquired during the treatment course. The original plan was re
calculated for each phase and deformably mapped to the reference phase to compare
the 'delivered' dose distribution with the planned dose distribution of both the
IMRT plan and the proton plan for each patient. DVHs derived from delivered dose
distribution were compared to that from the planned dose distribution. RESULTS:
The delivered dose showed 3% and 2% increase in the dose to the CTV for IMRT and
proton plan respectively. Target coverage remained acceptable despite tumor
shrinkage from 29% to 49%. The doses to normal structures, such as lung and
heart, increased more in the proton plan than in the IMRT plan. The V20 of the
total lung volume increased by 4% and 6% from the delivered dose compared to the
planned dose for IMRT and proton plan, respectively. CONCLUSIONS: The results
showed sufficient target coverage was maintained for both modalities. Increases
in lung dose were observed in both modalities, but more in the proton arm,
perhaps due to weight loss and tumor shrinkage. Adaptive proton therapy strategy
is recommended to minimize normal tissue doses. Supported in part by NCI P01
CA021239-29A1.
PMID- 28517187
TI - SU-E-T-439: First Experience of Three Dimensional Conformai Radiotherapy (3DCRT)
Planning with Helical Tomotherapy.
AB - PURPOSE: A three-dimensional conformal radiotherapy (3DCRT) has been recently
introduced to helical tomotherapy, allowing the user to plan and treat patients
that do not require sophisticated IMRT planning and delivery. This study aims to
test treatment planning on this modality and evaluate its performance by
comparing to conventional LINAC-based 3DCRT planning. METHODS: Four clinical
cases (whole brain, extremity, lung, and partial breast irradiation) were
retrospectively selected from a Pinnacle planning system (Philips Medical System,
Fitchburg, WI) and planned on Tomotherapy (Accuray Inc., Sunnyvale, CA). Computed
tomography (CT) images together with contours of target and critical structures
were exported from Pinnacle to the Tomotherapy planning station. The same
prescription and fractionation scheme was adopted. The pitch factor for all
clinical cases was set to 0.287. A 2.5 cm jaw was employed except in the lung
case the field size was set to 1.0 cm for better dose conformity. The dose grid
size was chosen to be half of that of the planning CT images. On Pinnacle 100%
prescription dose was delivered to the treatment isocenter while onTomotherapy it
was stipulated that at least 95% of the target volume received the prescribed
dose. Comparison between two planning strategies was performed, in terms of dose
volume histograms (DVH), dosimetric and radiobiological parameters, for plan
quality assessment. RESULTS: Comparison of DVHs reveals that up to 25% healthy
tissue sparing in volume can be accomplished with Tomotherapy 3DCRT while the
same target coverage is ensured. Dosimetric and radiobiological indices between
Tomotherapy and Pinnacle planning agree to within 3.0%. Additional beam modifiers
and non-coplanar beams associated with LINAC-based 3DCRT are not needed on
Tomotherapy, making it more favorable. CONCLUSIONS: Tomotherapy 3DCRT has similar
dosimetric performance when compared to conventional LINAC-based 3DCRT while it
is substantially easier to use.
PMID- 28517188
TI - SU-E-T-405: A Whole-Procedure Winston-Lutz Test for Quality Assurance of a Bite-
Block Based Extend Frame System for Delivering Multi-Session Stereotactic
Radiosurgery.
AB - PURPOSE: To develop a whole-procedure Winston-Lutz (WL) test method to determine
the full system accuracy of a vacuum-assisted bite-block based frame system for
multi-fraction Gamma Knife radiosurgery in reference to standard metal frame
based single fraction delivery. METHODS: A patient- specific bite-block frame was
first modified to incorporate a pin mark and a slanted film holder. Using actual
treatment protocol, a frame-indexed CT study was obtained and a treatment plan
was developed accordingly. Then a film was placed and exposed to the pin-point
position as identified per plan. To minimize signal noise for the exposed film
where isodose distributions were mostly non-spherical, a band of peripheral dose
distribution in the range of 40%-60% of central dose was extracted and then the
average center-of-mass position from the dose band was measured and compared
against the pin-point position. The test was carried out for initial system
commissioning as well as patient-specific quality assurance measurements.
RESULTS: Unlike traditional WL test where the border of an exposed field must be
precisely demarcated, our current procedure eliminates such requirement via
averaging a peripheral band of measured point cloud. The final result was more
robust against random noises and artifacts associated with scatter radiation and
signal processing. The mean variation against varying bandwidth and repeated film
exposures was found to be within 0.05+/-0.11 mm. For the initial 21 independent
treatment deliveries as tested at our institution, the overall system accuracy
was 0.36+/-0.11 mm, which matched excellently with 0.29+/-0.19 mm as measured for
a rigid metal frame. CONCLUSIONS: A robust CT-based Winston-Lutz test procedure
was developed for a multi-session bite-block based stereotactic frame system.
Submillimeter physical accuracy was established for such a system in a clinical
setting.
PMID- 28517189
TI - SU-E-T-387: Validation of a New System for Patient Specific IMRT QA and
Comparison with Other Commerical Systems.
AB - PURPOSE: The focus of this project is to compare the Octavius 4D with current
commercial available dose validation systems: MatriXX MultiCube and Delta4.
METHODS AND MATERIALS: Many challenges are faced with properly measuring
Intensity Modulated Radiotherapy (IMRT). It has become common practice for
clinics to use film, arrays, or multiple detectors to validate dose measurements
pretreatment for static and dynamic treatments. IMRT QAs for various treatment
sites were measured for patients using three different dose validation systems.
All measurements were taken on a Varian CLinac 2100 C/D, SN-757, 80 MLC with 6MV.
The treatment plans evaluated were Step-N-Shoot. Data analysis was performed
using the software provided with each dose validation system. Detailed
information was gathered from each system with their perspective advantages. The
latest system, Octavius 4D, allows one to calculate the Gamma Index for Coronal,
Sagittal, and Transversal views for every slice included in the measurement along
with the traditional data analysis provided; histograms, horizontal and vertical
profiles, DTA. RESULTS AND DISCUSSION: The Gamma Index values were observed using
the MatriXX Multicube, Delta4, and Octavius 4D. The treatment plan included five
fields at various gantry angles. Also the gamma index and profiles were
calculated for various treatment sites. Delta 4 and the Octavius 4D appears to be
quite comparable. Each device has the ability to allow one to verify segmented
and composite fields, measure dose profiles and analysis using the Gamma Method.
ConclusionsSimilar IMRT QA measurements will be made for more Step-N-Shoot cases
with the addition of SmartArcs. The limitations of each system will be determined
for each system using the Gamma Index as a reference while varying the Region of
Interest, Threshold, and Gamma Method (local, normalization, and maximum dose),
as well as the 2D- profiles for these cases.
PMID- 28517190
TI - SU-E-T-398: Verification of Gamma Knife EXtend System Based Fractionated
Treatment Planning Using EBT2 Film.
AB - PURPOSE: To present EBT2 film verification of treatment planning with the eXtend
System, a relocatable frame system for multiple-fraction or serial multiple
session radiosurgery. METHODS: A human head shaped phantom simulated the
verification process for fractionated Gamma Knife (GK) treatment. Phantom
preparation for eXtend Frame based treatment planning involved creating a dental
impression, fitting the phantom to the frame system, acquiring a stereotactic
computed tomography (CT) scan. A CT scan (Siemens, Emotion6) of the phantom was
obtained with following parameters: Tube Voltage - 110 kV, Tube Current - 280 mA,
pixel size - 0.5 mm * 0.5 mm and 1 mm slice thickness. A treatment plan with two
8 mm collimator shots and three sector blocking in each shot was made. Dose
prescription of 4.0 Gy at 100% was delivered for the first fraction out of the
two fractions planned. Gafchromic EBT2 film (ISP Wayne, NJ) was used as 2D
verification dosimeter in this process. Films were cut and placed inside the film
insert of the phantom for treatment dose delivery. Meanwhile a set of films from
the same batch were exposed from 0 Gy to 12 Gy doses for calibration purpose.
EPSON (Expression 10000XL) scanner was used for scanning the exposed films in
transparency mode. Scanned films were analyzed with in-house made Matlab codes.
RESULTS: Gamma index analysis of film measurement in comparison with TPS
calculated dose resulted in high pass rates >90% for different tolerance criteria
of 2%/2mm, 1%/1mm, and 0.5%/0.5mm. The isodose overlay and linear dose profiles
of film measured and computed dose distribution on sagittal and coronal plane was
in close agreement. CONCLUSIONS: Through this study we propose a treatment
verification QA method for eXtend frame based fractionated Gamma Knife
radiosurgery using EBT2 film. Acknowledgement: Authors acknowledge the help of
Andre Micke, ISP for sharing his expertise on EBT2 film.
PMID- 28517191
TI - SU-E-T-409: A Comparison of 3D Optical Surface and IR Marker Tracking for Head
Motion Compensated Frameless SRS.
AB - PURPOSE: Both infrared marker and 3D facial surface tracking were performed
simultaneously on both a head phantom and healthy volunteers. Accuracies of the
two 6D real-time tracking systems were quantitatively assessed both spatially and
temporally. The suitability of 3D facial surface tracking for providing real-time
head positioning to guide a robotic head motion compensation stage was
investigated. METHODS: A xyz stage was programmed to move a head phantom to
approximately 200 points in 10*10*10 mm3 and 100*100*100 mm3 cubic volumes,
respectively. Both 3D surface and IR marker tracking were performed
simultaneously on the head phantom to allow direct comparison of spatial
accuracy. Sinusoidal motion was performed along all three axis directions and
recorded under the same clock cycle. Spatial and temporal accuracies on actual
deformable facial surfaces were assessed by simultaneous 3D surface and IR marker
tracking on human volunteers. 3D surface tracking both with and without the use
of robotic head motion compensation was evaluated. RESULTS: For 10 samples at
each position, the 10 mm cube had RMSE of 0.30 mm and 0.08 mm for the AlignRT and
Polaris, respectively. Temporal lag of the AlignRT system was found to be
approximately twice the fps time (t_{lag} ~ 2/fps). The fps value was found to be
strongly correlated with region-of-interest (ROI) surface size and could vary
from 0.5 - 1.6 fps, leading to a lag time of 1 - 4 s. The Polaris output lagged
behind the reference by 0.06 s in all cases. CONCLUSIONS: Both 3D surface and IR
marker devices demonstrate high spatial accuracy for phantom based studies,
however, a slight dimensional warping along the SI direction was observed to
occur with the AlignRT. The current ROI dependent lag time of the AlignRT could
also pose an issue for image guidance techniques requiring quick response times.
PMID- 28517192
TI - SU-E-T-412: Can Cyberknife SBRT Be an Alternative to Brachytherapy for Cervical
Cancer Treatment?
AB - PURPOSE: To investigate the effectiveness of stereotactic body radiation therapy
(SBRT) with Cyberknife for treatment of squamous cell carcinoma (SCCa) of cervix
that are commonly treated with brachytherapy. METHODS: SCCa of cervix is
routinely treated with external beam radiation therapy (EBRT) followed by
brachytherapy. Common practice is to use high-dose- rate (HDR) brachytherapy,
mainly with Ir-192; however, low-dose-rate (LDR) brachytherapy with Cs-137 is
also used. Three of our patients with cervical SCCa who were chosen to have LDR
brachytherapy (Cs-137 with tandem and ovoids) could not tolerate the prolonged
treatment or applicator placement. All these patients previously received 45Gy
(1.8Gy/fratction) from EBRT and well tolerated. Planned LDR treatment dose and
time were for patient-1: 42.63Gy in 73.5hr, patient-2: 42.34Gy in 73hr, patient
3: 41.76Gy in 72hr. Delivered LDR dose and time were: 3.75Gy in 6.5hr, OGy in
Ohr, and 17.3Gy in 19.8hr, for patient-1, -2 and -3, respectively. Two of the
three patients tolerated LDR treatment partially; the second patient could not
tolerate the applicator, which required immediate removal after placement.
Treatments were completed with Cyberknife SBRT (CK-SBRT)doses of 25Gy, 15Gy and
25Gy for patient-1, -2 and -3, respectively; all had 5Gy/fraction and
3fractions/week. Prescriptions were at 80% isododelines; CTV coverages were
96.6%, 99.9% and 100% for patient-1, -2 and -3, respectively. RESULTS: Till their
last follow-up in February 2012, all three patients were doing fine clinically
without any evidence of disease; none of these patients had any complications
that could be related to CK-SBRT. CONCLUSIONS: Appears that CK-SBRT can be a
viable treatment alternative to brachytherapy. CK-SBRT may also be more appealing
to patients and physicians for a variety of reasons such as out-patient
procedure, shorter treatment time, no need for operating room, and no need for
applicator insertion and tolerance. However, extensive clinical study is
warranted in this regard.
PMID- 28517193
TI - SU-E-T-423: Dosimetric Effect of Rotation on Stereotactic Body Radiotherapy
(SBRT) of the Spine.
AB - PURPOSE: To study the dosimetric effects of the residual setup rotation errors in
spine SBRT. METHODS: We selected 25 patients with 26 lesions from an IRB approved
registry. All patients were setup with Exactrac IGRT and treated with Novalis.
Excatrac provided 6D shifts (3 translational, 3 rotational). The translational
shifts were corrected by moving the couch. The rotational shifts >2 degrees were
corrected by repositioning the patient, while smaller shifts were ignored. For
each patient, we rotated the simulation CT rigidly around the CTV center by the
recorded residual angles, using the MIM 4.22 software. The resulting rotated CT
with all contours were imported into the TPS. The clinical plans used for
treatment were mapped onto the rotated CT. Dosimetric endpoints were extracted
for the rotated CTV (mean, max, D90) and the rotated cord (D0.1cc, D1cc, V10,
max). These endpoints were compared to those from the clinical plan. RESULTS: For
the CTV, the average ratio of the mean doses was 1.001 (0.996-1.004), the average
ratio of D90 was 1.003 (0.998-1.011), and the average ratio of the maximum doses
was 1.005 (0.995-1.029). For the cord, the average ratio of DO.lcc was 1.01 (0.94
1.06), the average ratio of D1cc was 1.036 (0.92-1.23), the average max doses
ratio was 1.03 (0.95-1.11), and the average V10 ratio was 1.43 (0.56-2.78).
CONCLUSIONS: Rotational errors in patient setup as small as 2 degrees do have
dosimetric effects in spine SBRT treatments. The use of a robotic table to
eliminate translational and rotational shifts is strongly recommended. It is
important to note that, eventhough, the residual rotations resulted in up to 11%
variation (cord max dose) from the planned doses, none of these cases violated
our clinical treatment plan acceptance criteria (tolerance of the critical
organs).
PMID- 28517194
TI - SU-E-T-434: Use of Deformable Registration for Cumulated Dose Calculation in
Image-Guided Intracavitary Bracytherapy for Cervical Cancer.
AB - PURPOSE: The minimum dose to 2 cc of tissue receiving the highest dose (D2cc) has
been suggested as a surrogate measurement for risk of developing toxicity in
organs at risk (OARs) in patients receiving image-guided cervical intracavitary
brachytherapy. Conventional D2cc is typically calculated by simple summation,
assuming the locations of the hot spots do not vary substantially. This study
explores the effect of deformable image registration in determining a more
accurate D2cc of rectum, sigmoid colon, bladder and small bowel. METHODS: Five
patients, with 2 pelvic CT scans each performed at the time of brachytherapy
planning, were evaluated. The first scan was performed with an empty bladder (an
indwelling catheter was in place) and the second with a full bladder (with 180-cc
sterile water). OARs were contoured on each scan. A symmetric demons algorithm
with weighted sub-area approach was used to register images from different
fractions. A pelvic prostate phantom was used to verify the method. After
registration, the cumulated D2cc (ND2cc) was compared to the conventional D2cc
(OD2cc) without deformable registration. RESULTS: In all cases, the ND2cc was
lower than the OD2cc. For full bladder scans, the average difference (range) for
rectum, sigmoid colon, bladder and small bowel between ND2cc and OD2cc were 28.9
(1.6 - 56.6)%, 34.7 (5.7 -68.4)%, 12.1 (0.0 -27.7)%, 7.2 (1.1 -22)% respectively.
For empty bladder scans, the average differences (range) for the above organs
between the ND2cc and the OD2cc were 30.7 (0.75-56.3%, 20.6 (6.3-39.6)%, 7.5
(0.88-13.1)%, 12.2(0.0-22.2)% respectively. CONCLUSIONS: A significant difference
was observed between the ND2cc and the OD2cc with rectum and sigmoid being the
most variable and bladder the least variable. While further studies are needed to
evaluate which D2cc method is more useful in predicting late toxicity, we found
the conventional method often overestimates dose to OARs.
PMID- 28517195
TI - SU-E-T-416: Performance Test Comparing Three Pre-Treatment Isocenter Localization
Techniques for Single Fraction Cranial Stereotactic Radiosurgery.
AB - PURPOSE: To develop a performance test comparing three pre-treatment isocenter
localization techniques when using head-frame vs. immobilization mask for cranial
Stereotactic Radiosurgery (SRS). This study will compare pre-treatment
positioning techniques using laser alignment vs x-ray verification using ExacTrac
or On Board Imaging. METHODS: A RANDO anthropomorphic head phantom was fitted
with an in-house polystyrene insert to allow EDR2 film measurements in two
orthogonal planes. A pin hole was pricked on each film to serve as a target
during treatment planning. for each trial (three total), a CT scan was acquired
of the phantom equipped with either an immobilization mask or invasive head
frame. Treatment planning employed iPlan Image v4.1 and iPlan Dose v4.1.1.
Positioning of the phantom equipped with the head-frame was performed by aligning
vault lasers to coincide with cross-hair labels on a target positioner box.
Setups utilizing an immobilization mask were verified by x-ray verification using
ExacTrac and On Board Imaging, and if alignment were not within tolerance, then
shifts were made using a 6D robotic couch. Gantry star-shot irradiation was
performed using a 5mm cone to evaluate the differences between radiation
isocenter and the target. The mean and standard deviations were calculated for
differences in the x-, y-, and z-coordinate axes. RESULTS: Positional accuracy
using ExacTrac for mask based SRS resulted in 1.10+/-0.86, 0.67+/-0.83, and
0.59+/-0.48mm for cross plane, inline, and vertical measurements, respectively.
Differences for frame based SRS were 0.93+/-0.43, 0.76+/-0.18, and 0.34+/-0.12mm
for cross plane, inline, and vertical measurements, respectively. Results for
mask based SRS using OBI will soon follow. CONCLUSIONS: Although the frame-based
SRS techniquegenerated smaller standard deviations, the mean difference from
target to radiation isocenter for both techniques fall within the statistical
uncertainty of one another. Planning margins must take into account target size
when treating small lesions for both techniques. Project funded by CARTI.
PMID- 28517196
TI - SU-E-T-383: Pulsed Low Dose Rate Radiotherapy Using Advanced Treatment Methods: A
Novel Technique for Patient Re-Irradiation.
AB - PURPOSE: Pulsed low dose-rate radiotherapy (PLDR) re-irradiation has the
potential to reduce late normal tissue toxicity while still providing significant
tumor control for recurrent cancers. In contrast to conventional treatments
delivered at dose-rates of 400-600cGy/min, PLDR treatments deliver 20cGy pulses
separated by 3-minute intervals to achieve an effective-dose-rate of 6.7cGy/min.
This work aims to investigate the planning strategy and delivery quality of PLDR
treatment using IMRT and RapidArc techniques. METHODS: Twenty cases (10 treated
with PLDR IMRT, 10 for evaluation purposes) were recruited in this study
including prostate, pancreas, lung, head-and-neck, breast and pelvis. IMRT and
the RapidArc treatment plans were generated using the Eclipse TPS. For IMRT
treatment, each plan consisted of 10 fields to achieve a daily dose of 200cGy.
The breast IMRT and the RapidArc plans consisted of two fields/arcs, respectively
(40cGy/plan) and were delivered 5 times. The dose contribution from each field to
the planning target volume (PTV) was analyzed to evaluate the feasibility for
PLDR treatment. Machine-operation- dose-rate and plan quality was also
investigated. Dose delivery accuracy was assessed using a cylindrical diode
array. RESULTS: Throughout the six treatment sites, the mean PTV dose ranged from
16.1 to 26.1cGy/arc for RapidArc plans and 10.3 to 36.7cGy/field for IMRT plans.
For IMRT, the PTV dose contribution from each field strongly depends on the beam
arrangement and optimization parameters. With very low dose for a full rotation
(~ 20cGy/arc), the machine-operation-dose-rate of RapidArc plans significantly
affects plan quality and deliverability. A machine-operation-dose-rate of 100
MU/min results in superior delivery accuracy (>97.7% gamma-passing-rate for
3%/3mm criteria) for both IMRT and RapidArc plans. CONCLUSIONS: PLDR radiotherapy
using IMRT and RapidArc techniques Result in both dosimetric and radiobiological
benefits, which may have great potential for those previously-irradiated patients
who have historically done poorly.
PMID- 28517197
TI - SU-E-T-427: Effect of Contrast in Radiadyne Alatus Balloon Packing System on
Bladder and Rectal Doses in Gynecological Brachytherapy.
AB - PURPOSE: Vaginal packing for gynecological brachytherapy is used to immobilize
the applicator and reduce doses to the bladder and rectum by increasing the
separation from the applicator. With the introduction of theRadiadyne AlatusTM
balloon packing system, we evaluate further reductions in dose to these
structures by increasing the concentration of contrast in the balloon, increasing
its attenuation. This evaluation has been performed using the AcurosTM dose
calculation algorithm. METHODS: A patient with cervical cancer was treated with
HDR Ir-192 by insertion of a tandem and ovoid applicator, with the AlatusTM
balloon system used for vaginal packing instead of wet gauze. The balloons were
filled with distilled water containing 10% Omnipaque contrast. Retrospectively,
the balloons were contoured in the BrachyVisionTM planning system, and the CT
number of the structure set was adjusted to determine the effect of the
concentration of the contrast in the balloons on bladder and rectal doses after
heterogeneity correction using the AcurosTM algorithm. RESULTS: Use of 10%
Omnipaque solution reduced the bladder and rectal point doses by 6% and 9.5%,
respectively, with similar reductions in the D2cc and D1cc for each structure.
Overriding the density of the balloon showed that a 50% solution would reduce the
doses by 8% and 30%, respectively, due to the positions of the balloons with
respect to the applicator dwell positions. CONCLUSIONS: Use of the AlatusTM
balloon packing system allows reduction of the bladder and rectal doses both by
increasing the distance between the bladder and rectum and the applicators and by
increased attenuation of the dose by the use of contrast solution. Optimal
dilution of the contrast should take into account both the positive protective
effect of the solution as well as any negative artifact that the solution causes
in the CT scan, which might obscure the patient's anatomy patient.
PMID- 28517198
TI - SU-E-T-393: Using TG119 to Assess RapidArc at Hamad Medical Corporation.
AB - PURPOSE: To provide a confidence level within our clinic relating to the
implementation and administration of RapidArc, the AAPM TG1 19 has been
implemented. This task group provides a sound and relatively simple methodology
for determining the accuracy of the overall IMRT process administered in the day
to-day clinicMethods: Six different test plans, of varying complexity, were
created on mock structure sets, downloaded from AAPM, and delivered. The
treatment planning system results were then compared with the delivered results.
Plans were created and delivered on a solid water phantom, using 25*25cm water
equivalent slabs of varying thicknesses. Delivered point and planar dose
measurements were obtained using an ionization chamber and film, respectively.
RESULTS: The confidence limit (CL), averaged for all test plans, was calculated
for the high dose point in the PTV and for the low dose point in the avoidance
structure. This was used as an indicator of the uncertainty of the average
difference between measured and planned dose. Where the precision of the delivery
is based on how small the CL value is.For both the high and low dose points, the
local CL's were determined to be 0.036 and 0.011, respectively. The range of
results for the CL presented in TG1 19 varies from 0.015 to 0.098 for the high
dose point, and from 0.014 to 0.086 for the low dose point. CONCLUSIONS: Our
results indicate the accurate implementation of RapidArc within our clinic,
especially when compared to the results of other institutions, published in TG1
19. Furthermore, the CL value for the low dose measurements is lower than any of
the results published in TG119. We recommend that any clinic conducting IMRT
should implement this task group. This will not only provide a greater
understanding of the delivery and its limitations, but will also give the overall
accuracy and consistency of the technique as it applies to the various treatment
sites.
PMID- 28517199
TI - SU-E-T-438: Optimal Proton Beam Energy to Treat Adult CNS, Adult Head and Neck,
and Pediatric Cancers.
AB - PURPOSE: Proton therapy machines with lower beam energy requirements are expected
to be easier and more cost-efficient to design, construct, and operate,
particularly when using novel proton acceleration technology (e.g., dielectric
wall). We determine, for adult central nervous system (CNS) and head and neck
(HN) and pediatric cases, the optimal proton beam energies that can lead to
clinically acceptable plan quality. METHODS: Proton treatment plans for various
adult CNS and HN and pediatric cases, previously treated at our institution using
helical tomotherapy, were generated using a commercial planning system (XiO, v.
4.62, Elekta) with a passively-scattered proton beam model. Proton beam
orientations were chosen such that the distance from the skin to the distal
target edge was minimal; however, beams could not pass through areas with
significant surface irregularity (e.g. ear), nor through OARs with strict dose
limitations (e.g. lens). For a given beam direction, the planning system would
calculate an optimum range and modulation to cover a given target volume. Beam
weights were adjusted so that 95% of the target volume received the prescribed
dose. All plans were limited to two proton beams. RESULTS: An optimal proton
energy exists for each case studied. Among all cases, target dose conformity (the
ratio of target volume to volume encompassed by theprescribed dose) ranged from
0.74 to 0.94, and target dose uniformity (the ratio of the D5 and D95 doses)
ranged from 1.01 to 1.04, with the optimal proton energies. Among the CNS and HN
cases and for most pediatric cases, the maximum proton energy required was 133
MeV. For a pediatric abdomen case, 159 MeV protons were required. CONCLUSIONS:
For protontreatment of most adult CNS and HN and pediatric cases, the optimal
energies that are capable of generating good quality plans are only as high as
130 MeV.
PMID- 28517200
TI - SU-E-T-404: A Prototype Program for Analyzing 4D Image Guidance Shifts for Lung
SBRT.
AB - PURPOSE: A prototype in-house program was developed to assist deriving image
guidance shifts clinically using our 4DCT method for lung SBRT. METHODS: Our in
house prototype program was implemented in MATLAB. The 4D DICOM CT dataset of
interest is imported by the program from AW and subsequently accepts input from
the user regarding the desired relative IGRT shifts. The DICOM header information
defining the relative 4D dataset origin is then read in and the desired relative
IGRT shifts are applied to re-define the origin for the dataset that is to be
shifted. Lastly, the redefined (shifted) origin coordinates are written to the
header of the 4D dataset and the dataset is then exported to AW as DICOM files.
We used this program to process 4DCT datasets for four patients with 3-5
fractions each. The clinical shifts that were derived previously, without this
program, were applied to the images and the acceptability of these shifts were
evaluated. RESULTS: All slices and planes of the shifted 4D dataset were reviewed
and, in general, demonstrated acceptable re-centering of the target within the
ITV. However, it is noted that some small adjustments to the shift coordinates
would likely have been made had we had the opportunity to visualize the shifted
4D dataset as facilitated by the new in-house software. The additional
adjustments for the four patient cases studied here had an average of lmm and
maximum of 2mm in three principle directions. We look forward to exploring the
potential for implementing this software into our clinical workflow, and we
believe that such a workflow is worthy of consideration by vendors for
implementation as an available feature in future versions of their software.
CONCLUSIONS: We presented a prototype program to shift 4DCT image set for lung
SBRT applications and demonstrated four clinical cases.
PMID- 28517201
TI - SU-E-T-420: Development of a Comprehensive Linac-Based Quality Assurance
Procedure for Retrofitted Micro-MLC SRS System.
AB - PURPOSE: To develop a QA tool and methodology to be used with an Elekta SL 25
Linear Accelerator retrofitted with a 3DLine Micro-MLC gantry attachment in a
room installed with the 3DLine Dynatrac camera localization system Methods: A
phantom wa manufactured from clear polyester casting resign. This phantom was
designed to fit within the localizing head frame to test the accuracy of the
3DLine camera system in terms of isocenter localization. The phantom was aligned
using the imported isocenter coordinates from the ERGO++ TPS. The phantom
consists of metallic wires intersecting at the center and extending outwards to
the center of each of the six sides of the cube. Gafchromic film was taped to
each side and the cube was irradiated at different gantry and couch angles to
verify isocenter accuracy to within 1mm in accordance with TG 142. The films were
analyzed with RIT113 software, using the 50% isodose curves as the field edges
and the center of the field as marked by each of the wiresextending outwards from
the isocenter. RESULTS: Prelimina ry results of this isocenter test with the
retrofitted Micro-MLC gantry head attachment show a deviation of .72mm and -1.25
in the * and y directions respectively for the 90 degrees gantry angle. A
deviation of -1.27mm and -2.35mm in the x and y directions, respectively were
measured for the 270 degrees gantry angle. The additional sides will be
irradiated and their results along the results of the additional tests will be
presented at the AAPM national conference. CONCLUSIONS: After successful
completion of the above procedures for SRS QA, it was determined that the phantom
made with the localization wires can indeed be used to accurately and efficiently
QA a linac-based SRS system for isocenter location accuracy.
PMID- 28517202
TI - SU-E-T-386: Gamma Analysis of Normalized and Un-Normalized Dose Distributions.
AB - PURPOSE: The gamma index method, as currently implemented in all commercial QA
software, calls for selection of a normalization point to evaluate agreement
between two dose distributions. The implication of this is that there is an
infinite number of possible solutions! Which one to pick? A unique and more
relevant solution is obtained only if no normalization point is used. METHODS AND
MATERIALS: The set of test cases suggested by the AAPM TG1 19 were planned using
Pinnacle 8.0m and delivered on a Varian 21EX linac for 6 and 18 MV photons. The
recommended point and planar dose measurements were obtained using a Pinpoint ion
chamber, EDR2 film and MatriXX. The gamma index method using typical 3%, 3 mm
criteria with and without a normalization point was used to assess the agreement
between calculated and delivered planar dose distributions. The analysis was
extended to a set of data for clinically treated patients. RESULTS: The
comparison with the TG119 benchmark data showed that all point dose and planar
measurements for 6 MV were within the published range. Similar results, although
without published data to compare with, were obtained for 18 MV as well. For all
complex tests, the percentage of points passing the gamma criteria of 3%, 3 mm
was (95.8+/-1.6)% and (95.6+/-1.0)% for 6 MV and 18 MV, respectively. Without a
normalization point, however, the same gamma analysis fell to (20.7+/-6.7)% and
(13.9+/-4.0)% for 6 MV and 18 MV, respectively. The clinical data set showed the
same trend, with the gamma passing rate declining from (98.9+/-0.7)% to (33.4+/
13.1)%. CONCLUSION: The gamma index method provides a unique answer for gamma
passing rate only without normalizing dose distributions to any particular point.
The common gamma criteria of 3%, 3 mm, however, is a very poor metric in that
case.
PMID- 28517203
TI - SU-E-T-397: Interplay Effect of Gated Lung Stereotactic Body Radiotherapy with
RapidArc Delivery.
AB - PURPOSE: To investigate the dosimetric effect of intrafraction tumor motion
during gated RapidArc Stereotactic Body Radiotherapy (SBRT) delivery. METHOD: The
realtime tumor motion data were retrieved from 6 lung patients. Each of them
received 3 fractions of stereotactic radiotherapy treatments with Cyberknife
Synchrony. Phase gating through an external surrogate was simulated with a gating
window of 5 mm. The resulting residual tumor motion curves during gating (beam
on) were retrieved. RapidArc SBRT was planned on the platform of Varian Truebeam
at 6 MV with 1400 MU/min. Planning target volume (PTV) was defined as physician
contoured clinical target volume (CTV) surrounded by an isotropic 5 mm margin.
Each patient was prescribed with 60Gy/3 fractions. The RA plan typically consists
of 2 arcs; each contains 90-120 control points. An algorithm was developed to
reconstruct the delivered dose with tumor motion. The MLC segment is assumed to
move relatively to a static tumor. Each MLC control point, mainly the leaf
position were modified according to the probability density function of tumor
motion. The newly created MLC control points were written back to the treatment
file in the dicom format which was subsequently imported to treatment planning
system (Varian Eclipse) for dose recalculation. RESULTS: The magnitude of dose
deviation with motion is consistent with the excursion of the residual tumor
movement. Overall CTV coverage of the study group is barely affected owing to the
5 mm margin. The fractional PTV dose coverage dropped by 4% at most and that from
all fractions by 3%. An examination in the point dose shows an increase of 4% in
the maximum dose and decrease of 10% for the minimum dose. CONCLUSION: With
effective gating, interplay effect does not change the target coverage much
during gated RapidArc SBRT. However it increases the dose nonuniformity inside
target.
PMID- 28517204
TI - SU-E-T-408: Enhancing Stereotactic Radiosurgery for Neovascular Age-Related
Macular Degeneration, Using Gold Nanoparticles.
AB - PURPOSE: Age-related macular degeneration (AMD) is the leading cause of
irreversible vision loss for people over the age of 60 in the United States. In
this study the dosimetric feasibility of using gold nanoparticles (AuNP) as
radiosensitizers to enhance stereotactic radiosurgery for neovascular AMD is
investigated. METHODS: Analytic calculations were carried out to estimate the
nucleus dose enhancement factor (nDEF) due to photon-induced photo- /Auger
electrons from AuNP targeting neovascular AMD endothelial cells (EC). The nDEF
represents the ratio of the dose to the nucleus with and without the presence of
AuNP. As in previous studies, the EC is modeled as a slab of 2 MUm (thickness) *
10 MUm (length) * 10 MUm (width) containing a nucleus of 5 MUm diameter and
thickness of 0.5 - 1 MUm. The targeted AuNP are attached to the exterior of the
EC. The nDEF was calculated for a range of feasible AuNP local concentrations (1
7 mg/g) using the clinically applicable 100 kVp x-rays employed by the IRayTM
system (Oraya Therapeutics Inc. Newark, CA), with total filtration of 0.75 mm Al
and 0.8 mm Be. For comparison the nDEF for other energies: 80 kVp, 90 kVp, 110
kVp, and 120 kVp was also investigated. RESULTS: For 100 kVp x-rays, the results
revealed nDEF values of 1.30 - 3.26 for the investigated concentration range of 1
- 7 mg/g, respectively. In comparison, for the same concentration range, nDEF
values of 1.32 - 3.40, 1.31-3.33, 1.29 - 3.19, 1.28 - 3.12 were calculated for 80
kVp, 90 kVp, 110 kVp, and 120 kVp x-rays, respectively. CONCLUSIONS: The results
predict substantial dose enhancement to the sensitive nucleus of neovascular
endothelial cells, targeted by AuNP during kilovoltage stereotactic radiosurgery.
This suggests that AuNP may be employed as radiosensitizers to enhance
therapeutic efficacy during radiosurgery for neovascular AMD.
PMID- 28517205
TI - SU-E-T-390: Monitorization of the Dynamic Multi-Leaf Collimator Performance Using
Log Files - a Quality Assurance Tool for Intensity Modulated Radiotherapy.
AB - PURPOSE: Commission baseline values of the multi-leaf collimator (MLC) using
Varian's dynalog file viewer software (DFV) and establish tolerance levels to use
as a periodic quality assurance tool in intensity modulated radiotherapy (IMRT).
METHODS: A sliding window test was created to have all leafs moving at a constant
high speed of 2.5cm/s. This test was performed for 100 days at gantry angles of 0
degrees , 90 degrees and 270 degrees during the morning quality checks in an
accelerator performing RapidArc treatments with a Millennium 120 MLC. The DFV was
used to collect the percentage of counts in bins 1 (0.05mm) to 8 (deviations in
steps of 0.5mm) and the root mean square error (RMS). These were analyzed
statistically and a baseline value and tolerance levels were established.
RESULTS: Results show that the greater percentage of counts is found at bin 4
with an average of 97%. Bins 1 to 3 have less than 1 % and bin 5 presents an
average of 1.7%. As for bin 6, the average was below 0.1%. Bins 7 and 8 presented
no counts. When comparing the results of the different gantry angles, significant
differences are only found in bin 4 and 5, with a better performance for the 0
degrees gantry. As for the RMS error, no difference was found between different
carriages or gantry angles and the average value was 0.129. A tolerance level was
established for bins that correspond to greater deviations - bins 5 to 8, with an
upper limit equivalent to twice the standard deviation of each bin. CONCLUSIONS:
With the introduction of IMRT, the MLC quality assurance became more extensive
and thorough. However a quantitative analysis is often difficult to interpret and
time consuming. The purposed method allows the monitorization of the stability
and performance of the MLC in a quantitative and easy way.
PMID- 28517206
TI - SU-E-T-411: Dosimetric Comparison Between Two Multileaf Collimator Systems for
Stereotactic Radiosurgery and Radiotherapy.
AB - PURPOSE: This aim of this study is to compare the dosimetric parameters of two
multileaf collimator (MLC) systems: (1) the beam modulator (BM), which is the MLC
commercial name for Elekta 'Synergy S' linear accelerator; and (2) Radionics
micro-MLC (MMLC). METHODS: Dosimetric parameters of percentage depth dose (PDD),
in-plane and cross-plane beam profile, penumbra, MLC leakage and transmission for
a 6 MV photon beam with different field sizes and depths were measured using
ionization chamber, film, solid water phantom and water tank. At the same time,
the BM and MMLC were modeled using the BEAMnrc code and the above dosimetric
parameters were calculated using Monte Carlo simulations. Energy fluence spectra
for the two MLC were determined using the BEAMnrc and BEAMDP. RESULTS: We found
that dosimetric parameters (PDD, beam profile, energy fluence spectra, leakage
and transmission) of the two MLC were similar, except for penumbra. The leaf-side
and leaf-end 20%-80% penumbras at 10 cm depth for a 10*10 cm2 field were 4.8 and
5.1 mm for the MMLC and 5.3 mm and 6.3 mm for the BM, respectively. The maximum
percentage of the leakage for the BM and MMLC are 1.3% and 1.2%, while the
average percentage of leakage for the BM and MMLC are 0.9% and 1%. CONCLUSIONS:
Based on their dosimetric characteristics for stereotactic radiosurgery and
radiotherapy, it can be concluded that both the BM and MMLC can be used
effectively, though the latter showed slightly sharper dose penumbra especially
in the leaf-end direction. However, the BM has the advantages of producing
considerably larger field at isocenter and having a greater isocenter clearance
compared to the MMLC. The dosimetric data in this study should help radiotherapy
staff to appreciate dependence of dosimetry on the MLC design and configuration
for stereotactic radiosurgery and radiotherapy. Actual or potential conflicts of
interest do not exist.
PMID- 28517207
TI - SU-E-T-422: Lung SBRT Using Cyberknife: Technique and Treatment Outcome.
AB - PURPOSE: At East Carolina University, we have been treating primary and secondary
lung cancers with Cyberknife stereotactic body radiotherapy (CK- SBRT) since
February 2009. Till October 2011, we have treated a total of 79 patients (83
sites). In this study, we present our experience in CK-SBRT and clinical outcome
of the treated patients. METHODS: Of the 79 patients, 43 were female; age of the
whole patient population ranged 33.2-89.7yrs (median=73.2yrs). Patients treated
for primary lung cancer (n=57) had severe chronic obstructive pulmonary disease
(COPD) and were not surgical candidates. Cyberknife robotic system with tracking
techniques (Synchrony=52, XsiteLung=22, XsightSpine=5) were used. Majority of the
patient (n=52) had multiple gold fiducials placed (1-6 placed; 1-4 tracked per
patient) either percutaneously or bronchoscopically. CT images were used for
dosimetric planning, by medical physicists, using Cyberknife MultiPlan software.
Prescription doses were 25Gy-55Gy in 3-5 fractions (mean=48.2Gy, median=50Gy);
doses were prescribed mainly to 80% isodoseline (range=75-96%, mean=81.4%). PTV
margin varied from 0-7mm (mean+/-SD=3.2+/-1.4mm), based on the tumor locations;
breathing patterns and cancer type. Dosimetric coverage of GTV and PTV were
(mean+/-SD): 97.8+/-5% and 94.7+/-6.9%, respectively. The treatment response was
assessed using either a CT or a PET scan or both. RESULTS: The median follow up
was 13.1months (range 0.3-31.9 months). Overall response rate was 98.8%
(CR=73.5%). Local failure free survival at one year was 84% for primary (n=57),
76% for recurrent (n=16) lung cancer and 100% for metastatic (n=10) tumors. The
toxicity rate was low with one patient reported to have chest wall pain and one
patient developed grade 3-4 radiation pneumonitis. CONCLUSIONS: In most of the
cases tight PTV margins were used. Since the prescriptions were at 80% isodeose
line with more than 94% PTV coverage, the treatment outcome appeared reasonable.
Further study relating PTV margin, dosimetric coverage, and treatment outcome is
in progress.
PMID- 28517208
TI - SU-E-T-433: Pear-Shaped Based Dose Optimization for HDR Intracavitary
Brachytherapy for Cervical Cancer Patients with Small Uterus.
AB - PURPOSE: Currently, CT has been widely used for HDR planning as MRI is not widely
available for tumor imaging. Conventional pear-shaped isodose distribution may
not be discarded completely because of possible microscopic diseases into
parametrium/uterus. For patients with small uterus, organs at risk (OARs) can
fall inside 100% conventional pear-shaped isodose-line. This study compares two
pear-shaped based dose optimization methods for OARs sparing. METHODS: Seven
cervical cancer patients with small uterus were evaluated using 2 methods. For
Method A, with conventional dwell-time loading, point A lateral distance was
reduced until all OARs' D2cc were within the dose limits. For Method B, a
reference target volume was generated using conventional pear-shaped 100% isodose
surface. While isodose-line near the point A was adjusted for OARs sparing,
isodose-line surrounding ovoids were optimized to match the reference target
volume. For equivalent OAR sparing, 100% isodose-line width (lateral dimension)
at 1 cm inferior to point A (-1 cm) and at across centers of ovoids (ovoid) were
compared between the 2 methods. RESULTS: OARs fall inside conventional 100%
isodose-line in all cases. Median position of hot spots was 0.2 cm (range -;1.2
to 2.9 cm) superior to point A. Using Method A, point A lateral distance was
adjusted to 1.4-1.7 cm for OARs sparing. Median width of 100% isodose-line was
5.82 cm at ovoid level, and 4.50 cm at -1 cm level. At ovoid level, median width
of 100% isodose-line was reduced by 9(8-13)% for Method A, and was unchanged for
Method B. At -1 cm level, median width of 100% isodose-line was reduced by 19(2-
33)% for Method A, and 11(0-15)% for Method B. CONCLUSIONS: for patients with
small uterus, OARs are often fall inside 100% pear-s haped isodose-line near
point A level. OARs can be spared without dramatically compromise treatment
volume coverage around cervix using Method B.
PMID- 28517209
TI - SU-E-T-415: Evaluation of the Effect of the Dose Buildup Region for Flattening
Filter Free Beams in IMRT Plans of Lung and Sinuses.
AB - PURPOSE: The surface and buildup dose is known to be greater for flattening
filter-free (FFF) beams as compared to flattened beams. We compare the effect of
this difference in the dose buildup region between the two beam modes, in the
context of IMRT plans for the lung and sinuses. METHODS: IMRT plans are delivered
using both the standard flattened beam mode (6X) and flattening-filter-free mode
(6XFFF). We compare the dosimetric differences of these two modes, for IMRT
treatments for the lung and sinuses. Radiochromic films and parallel-plate
ionization chamber measurements were taken, and evaluated for the following field
sizes: 2*2 cm2 , 3*3 cm2 , 5*5 cm2 , 8*8 cm2 , 10*10 cm2 , and 20*20 cm2 . We
evaluated the area under the PDD curve (AUC) for the buildup region for both 6X
and 6XFFF beams. Ten SBRT lung and five IMRT sinuses plans were generated using
the EclipseTM planning system, commissioned with AAA. Plan evaluation involved
the comparison of the isodose distributions between plans of the two delivery
modes. RESULTS: For small field sizes, the dose in the buildup region is greater
for FFF beam than for flattened beam. The percentage differences between 6XFFF
and 6X flattened beams for the following field sizes (2*2 cm2 , 3*3 cm2 , 5*5 cm2
, 8*8 cm2 , 10*10 cm2 , and 20*20 cm2 ) are 3.4%,2.2%, 7.2%, 4.9%, 0.9%, and
0.5%, respectively. Plan evaluation of the IMRT sinus cases found approximately
3% higher maximum dose within the PTV for FFF plans. No observable differences
were found between two types of SBRT lung plans. CONCLUSIONS: For small fields,
the dose buildup region of FFF beam is slightly greater than that of flattened
beams. This effect is more pronounced in IMRT sinus cases, leading to higher dose
within the PTV. There was no difference in the SBRT lung plans between the two
beam modes.
PMID- 28517210
TI - SU-E-T-382: An Analysis of VMAT Monthly Quality Assurance.
AB - PURPOSE: The purpose of this study is to quantify the change in monthly VMAT
quality assurance (QA) and determine the tests to maintain consistent delivery
with a baseline. METHODS: VMAT monthly QA has been performed for over 14 months
on two Elekta Synergy LINACs. A baseline was established at acceptance and the
monthly QA results were compared to those initial values. Films were used to test
the dependence on varying dose rate, gantry speed, rotational direction, and MLC
speed. These parameters were tested independently and then together in a test
called the synchronicity test. Ion chamber readings test a DMLC field with a
varying dose rate and MLC speed. Introducing intentional errors into the tested
fields allowed the detectable limits of the QA to be determined. RESULTS: The
monthly QA has consistently matched the baseline within a 3% dose limit on film.
Analyzing the synchronicity film with a gamma test using a 5%/0.5mm tolerance
showed a monthly pass rate of over 99%. The DMLC test has been identical for the
entire course of VMAT QA. Furthermore, intentional changes in the MLC speed were
noticed on the synchronicity test in the form of a smaller gamma pass rate as the
MLC error was increased. CONCLUSIONS: There is a monthly agreement with all films
testing individual parameters, ion chamber DMLC readings, as well as agreement
with the synchronicity test. This collection of data has lead to the conclusion
that only the synchronicity test and DMLC readings need to be performed on a
monthly basis. If those tests fail, then individual parameters need to be tested
to determine the singular cause of the error. Having a single test used as a red
flag increases the efficiency of the monthly QA and is being implemented with an
EPID to eliminate the use of film.
PMID- 28517212
TI - SU-E-T-392: A Software Tool of Extracting Dose Plane for Tomotherapy Delivery QA.
AB - PURPOSE: To develop a software tool to extract dose planes base on on the setup
(red) laser positions for Tomotherapy delivery QA(DQA). METHODS: We have a
develop a simple tool to simplify a time-consuming step for tomotherapy DQA. The
DQA analysis tools in Tomotherapy software was useful for film dosimetry but not
convenient for 2D-array QA devices. Current DQA software requires the user to
perform alignments twice: one for setting DQA phantom and the other for
extracting dose plane. These two steps can be simplified into one if both
alignments are based on the central axis of the detector plane. Once the setup
(red) lasers are set for DQA, the dose plane can be extracted from the dicom dose
file and the dicom plan file automatically. An open source software was written
in C using dicomtk library. The accuracy of the program has been tested by
comparing the extracted dose plane to the same dose plane but extracted by the
manual method. RESULTS: The maximum dose difference is 0.5% and the mean
difference is 0.2%. The differences are probably due to the variation between two
manual alignments. The software extracts 2D-dose plane in a simple and automatic
way. This not only cuts workload but also reduce the degree of human error
because only one manual alignment is needed. A copy of this open source software
is available upon request. We also hope Tomotherapy provides similar function in
future upgrade. CONCLUSIONS: A software tool has been developed to simplify
Tomotherapy DQA procedure.
PMID- 28517211
TI - SU-E-T-426: Comparison of HDR Brachytherapy for Cervix Cancer Using an Adaptive
Simulated Annealing Program and Oncentra- for Simultaneously Integrated Boost.
AB - PURPOSE: High dose rate (HDR) volumetric brachytherapy is an effective method of
treating advanced cervix carcinoma. Local failure is associated with multiple
factors including higher maximal standardized uptake value (SUV) values in
fluorodeoxyglucose positron emission tomography (FDG- PET) scans. The purpose of
this study is to evaluate the ability to simultaneously boost regions of high SUV
values using an in-house adaptive simulated annealing (ASA) algorithm and the
Oncentra(r) (Nucletron V.B., Veenendaal, The Netherlands) treatment planning
system, thereby potentially improving local control. METHODS: Five cervix cancers
were evaluated for brachytherapy treatment (tandem/ring and/or interstitial
needles). MRI and PET images were obtained post-implant and fused with treatment
planning CTs to define a high-risk (HR) CTV (cervix and tumor on MRI) and GTV
(volume with >50% of the maximum SUV on PET). The prescribed dose was 5-6 Gy to
the HR CTV and 7-9 Gy to the GTV. Treatment plans were first generated in
Oncentra(r) with IPSA followed by manual graphic optimization by the physician.
Plans were also independently optimized using the ASA program. The two plans were
compared side by side and one was chosen for treatment. Dose-volume parameters
including D90, V100 of targets, D2cc to the critical organs, and generalized
equivalent uniform dose (gEUD) of all structures were compared between the ASA
and the Oncentra plans. RESULTS: Both ASA and Oncentra plans were considered
acceptable by the physician in four of five cases. Two ASA plans were chosen due
to better critical organ sparing and tumor coverage. Two Oncentra plans were
preferred because of lower doses to critical organs. One ASA plan was not
accepted because of a higher bowel dose. CONCLUSIONS: Both ASA and Oncentra(r)
planning methods produce acceptable treatment plans for optimized brachytherapy
of cervix carcinoma. Continued studies are warranted to further determine the
relative strength of each method. This study was supported in part by a research
grant from Varian Medical System Inc.
PMID- 28517213
TI - SU-E-T-437: Interfractional Dosimetric Verification of Lung Patients Treated by
Passive Double Scattering Proton Radiotherapy.
AB - PURPOSE: Proton radiotherapy, with the ability to confine the dose at desired
depth, can potentially benefit lung tumor patients by significantly sparing the
healthy lung tissue. However, the superior proton dose distribution could be
affected by tumor shrinkage due to the quick response and by motion especially
related to the respiration. Thus the treatment should be frequently verified and
be adjusted accordingly if necessary to achieve the initial treatment goal.
MATERIAL AND METHODS: A cohort of 20 patients were selected from lung patients
treated with passive proton radiotherapy. All those patients were evaluated via
4D-CT scans and found to have tumor motion less than 1 cm. The internal target
volumes (ITV) were derived based on the full inspiration and expiration phases.
The average of the 4D-CT scan, full inspiration and expiration phases were used
for the initial treatment planning. The planning objective was 95% of the
prescription dose to at least 95% volume of the ITV. Bi-weekly verification 4D-CT
scans were performed to assess the robustness of the initial treatment plan and
no replanning was required for target dose variations less then 3%. RESULTS:
Compared with the initial treatment plan, the standard deviations of target
coverage on inspiration, expiration, and average verification CT scans are within
3% for all the patients, with the maximum difference up to 7%. No statistically
significant differences were found among the initial and verification plans
(p>0.1). The percentage deviations of OAR sparing were highly variable, e.g., up
to 40% for mean lung dose, 100% for mean heart dose, 50% for max cord dose,
particularly for OARs receiving small amount of doses. However, the absolute dose
deviations are all with OAR's tolerance. CONCLUSION: Overall, the passive double
scattering proton modality allows for robust proton treatment planning and
delivery to treat the lung tumors with limited motion.
PMID- 28517214
TI - SU-E-T-403: Delivery Efficiency of StereoArc Stereotactic Body Radiotherapy
(SBRT).
AB - PURPOSE: Traditional SBRT employs approximately 10 static beams with up to 20 Gy
per fraction, requiring lengthy treatments which can be difficult for patients to
tolerate, increasing the risk of movement, and causing discrepancies in the
reproducibility of the breathing cycle. Commercial VMAT systems offer shorter
treatment times with modulated beams; however, modulation is often not necessary
or desired for small fields. Conformai arc therapy offers efficient beam
delivery, but with only one aperture shape and constant beam weighting over all
gantry angles. This study evaluates the efficiency of a new SBRT delivery Method:
a conformai arc with multiple aperture shapes and variable dose rate. METHODS:
Three clinical SBRT cases were chosen for this study. Each static field was
converted into an arc segment to create a StereoArc plan. Gantry angle ranges
were determined from the clinical monitor units, with the MU/degree chosen to
maximize the dose rate. All segments were merged into a single arc with variable
dose rate. Dose distributions from the StereoArc plans were compared to the
clinical static field plans using Pinnacle. Delivery times were compared between
the static SBRT plans, both with and without Beam Automation, and equivalent
StereoArc plans. All plans were delivered on a Varian TrueBeam using a dose rate
of 1000 MU/min. RESULTS: Dose differences between StereoArc and static plans were
minimal. Delivery times for the static plans were 5-8 minutes, while delivery
time with StereoArc was less than 3 minutes for all cases, which was equivalent
to delivering the static plans with Beam Automation. CONCLUSIONS: Delivery
efficiency was improved up to 60%: from 8 minutes for static fields, to less than
3 minutes for StereoArc. StereoArc appears to be both an effective and efficient
way of delivering SBRT for centers not wishing to modulate SBRT and without
access to Beam Automation. This study is partially supported by NIH grant
1R01CA133539-01A2.
PMID- 28517215
TI - SU-E-T-419: MU Verification for Small Lesions in Lung SBRT.
AB - PURPOSE: To determine if a secondary MU calculation can validate the treatment
planning system MU calculation for objects less than 4cm in diameter in small
field lung SBRT. To determine the small object modifier to better predict the
correct MU. METHODS: Four polystyrene spheres were embedded into lung mimicking
material. The sphere diameters are 4cm, 3cm, 2cm, and 1.2cm. The spheres are made
up of two dome TLD-100 chip holders. Each TLD holder holds two 0.125' square *
0.035' TLDs. The output (cGy/MU) was measured at the center of each sphere for
three depth and effective depth combinations. The depth, effective depth, field
size, and energy were kept constant. The effective depth was kept constant by
adding tissue equivalent water to the top of the phantom as the sphere diameter
got smaller. The three depths were 5cm, 10cm, and 15cm, with an effective depth
of 5cm, 6cm, and 7cm, respectively. The collimator field size and the effective
field size was 3cm * 3cm. The energy was 6MV. The measured results were compared
with the output predicted by our treatment planning system. RESULTS: Dose
measurements were made with both TLD and film and the results were averaged. The
secondary MU calculation predicted that the output would be the same for each
sphere. However, the measured output dropped as the sphere diameter got smaller,
especially for the 1.2cm diameter sphere. The output dropped by 5% at a 10cm
depth and by 9% at a depth of 15cm. CONCLUSIONS: Secondary MU calculations cannot
reliably predict the MU's for small objects less than 3cm in diameter without
modifiers. A modifier of 3% is needed for a 2cm sphere and 7% for a 1.2cm
diameter sphere.
PMID- 28517216
TI - SU-E-T-385: Accelerated Beam Delivery with MLC Gaps in IMRT Fields.
AB - PURPOSE: By default, the 4-mm wide leaf-pairs of the Elekta Beam Modulator MLC
not used for field shaping are moved to under the primary collimator to minimize
the leakage dose. The trade-off is the increased beam delivery time in the case
of IMRT. This study examines the dosimetric impact and improved delivery
efficiency by allowing the unused leaf-pair as 2mm gap to stay within the PTV
aperture during beam-on. METHODS: The capability of the treatment planning system
(Pinnacle) in modeling the central and off-axis dose through 2mm MLC gaps,
respectively, was investigated. EBT film measurement performed in a solid water
phantom was compared with the computed dose. For two representative IMRT cases,
the dosimetric features of treatment plans generated with and without MLC gaps in
the field were compared. Similarly, the delivery times for 13 IMRT cases with and
without MLC gaps were compared. RESULTS: The peak dose of the leaf gap computed
with Pinnacle was dependent on dose grid resolution. The difference between a
0.5mm and 2mm dose grid was about 16.5% for 6MV and 15MV beam respectively. Using
a 0.5mm dose grid, the maximum difference between measured and calculated dose
was < 1% for a central axis gap, and < 3% for an off-axis gap. The maximum dose
through a 2mm*4mm leaf gap was estimated < 10cGy for a typical IMRT plan. DVH
comparison showed an increase of target dose up to 2% for the IMRT plans with
gap, with minimal dose change to all critical structures. For the 13 IMRT cases,
the beam delivery times were reduced by 27+/-9.7%, from 8.7+/-4.5 minutes to
6.5+/-4.0 minutes. CONCLUSIONS: The beam delivery is accelerated by utilizing
minimal gaps in the IMRT fields. The increased dose to the target is acceptable
and is minimal to all critical structures.
PMID- 28517217
TI - SU-E-T-430: Evaluation of Inverse Optimization in Brachytherapy for Locally
Advanced Cervix Cancer.
AB - PURPOSE: Brachytherapy is a vital part of treating locally advanced cervix
cancer. Point-based 2D treatment planning is conventionally used. New CT/MRI
compatible applicators for HDR brachytherapy make 3D conformal planning possible.
GEC-ESTRO endorsed the EMBRACE (intErnational study on MRI-guided BRachytherapy
in locally Advanced CErvical cancer) protocol which recommends standard-plan
based manual optimization over inverse optimization due to the concern of the
uncertainty of high dose in targets and adjacent normal tissue. This study
investigated the feasibility of inverse optimization planning. METHODS: Eight
cervix cases using tandem/ring applicators +/- parametrial needles were
evaluated. Both manually and inversely optimized 3D conformal plans using
Oncentra(r) Brachy were generated for each case following EMBRACE guidelines.
Planning time and DVH parameters including D90 and V100% for HR-CTV, D90 for IR
CTV, D2cc for normal structures (bladder, rectum, sigmoid colon, and small bowel)
were compared. Dose was reported in total EQD2 dose, assuming 45Gy in 25
fractions external beam and 28Gy in 4 fractions HDR treatment. Prescription dose
(PD) and PD*2 isodose volumes and V100% and V200% for normal tissue (excluding
all contoured OARs) were compared to evaluate the high dose volumes. RESULTS: The
average planning time was reduced by 55% with inverse planning. Target coverage
between inverse and manual plans differed by <2% for HR-CTV (D90 and V100) and IR
CTV (D90). Inverse planning reduced the D2cc for normal structures by 4.2%-5.7%
and the V100% and V200% for normal tissue by 31% and 40%, respectively. For 7 of
the 8 cases, small bowel was observed near the target and received significant
dose with either approach. CONCLUSIONS: In this study, inverse planning improved
DVH parameters over manual planning, with less planning time. Reporting normal
tissue dose should alleviate the concern of undetected high dose regions. Even
though small bowel is not often considered in traditional planning, dose should
be reported.
PMID- 28517218
TI - SU-E-T-396: Beam Angle Optimization for IMPT Comparing Gantries and Fixed Beam
Lines.
AB - PURPOSE: To explore the potential of beam angle optimization (BAO) for IMPT and
compare fixed beamlines with gantries. METHODS: For three patients with
challenging intracranial lesions, we generate reference IMPT treatment plans
applying three manually selected beam orientations and treatment plans applying
three optimized beam orientations considering five scenarios: (1) patients are in
supine position and the treatment room features (1.a) a horizontal beamline,
(1.b) a horizontal, 45 degrees , and vertical beamline, (1.c) a gantry, (2)
patients are in supine or seated position and the treatment room features (2.a) a
horizontal beamline, or (2.b) a horizontal, 45 degrees , and vertical beamline.
We use a genetic algorithm that considers up to 1,400 non-coplanar candidate
beams and evaluates 10,000 beam ensembles for one BAO. Beam orientations that may
compromise the robustness of treatment plans are excluded before the optimization
based on an objective measure of existing tissue heterogeneities. RESULTS: The
optimized beam ensembles exhibit certain similarities even though the sets of
candidate beams differ significantly for the five scenarios. Compared to manually
selected beam orientations, they provide improved OAR sparing and equivalent
target coverage. Compared to one another, they yield comparable target conformity
(deviations of the conformity number <1%), target homogeneity (standard
deviations of the target dose <0.8 Gy), and sparing of OARs (deviations of
average mean and maximum doses in OARs +/- 1 Gy). Using a gantry, however, the
integral dose can be reduced by 5-15% compared to a horizontal beamline with
patients in supine position. For the investigated cases comparable reductions can
be achieved by also irradiating in seated position with a horizontal, 45 degrees
, and vertical beamline. CONCLUSIONS: BAO has the potential to provide beneficial
IMPT treatment plans. Compared to fixed beamlines, gantries yield only modest
effects regarding OAR sparing but may enable a significant reduction of integral
dose for individual patients.
PMID- 28517219
TI - SU-E-T-407: Freedom from Conventional: Application of RapidArc for SBRT Lung
Treatments.
AB - PURPOSE: Stereotactic body radiotherapy (SBRT) has been applied in treating early
stage small lung lesions, delivering hypofractionated doses in a conformai
manner. Studies have shown that SBRT has similar outcomes compared with surgery.
Conventionally, SBRT lung treatments rely on utilization of multiple small,
conformai, static fields in coplanar and non- coplanar arrangements. With the
advent of RapidArc, it is important to evaluate the differences in dosimetry and
delivery of conformai SBRT lung treatments for both conventional static field and
VMAT techniques. METHODS: A retrospective study of 12 patients at our institution
who have received SBRT for primary lung lesions was used to evaluate the
application of RapidArc for such cases. Originally treated plans utilized eight
to ten conformai static coplanar and non-coplanar fields. RapidArc plans were
generated in Eclipse using single and multiple arc setups. RESULTS: As an
ntensity-modulated modality, RapidArc provides greater freedom as compared to
conventional static field delivery, as one can achieve dose uniformity throughout
the PTV or replicate the dosimetry synonymous with conventional SBRT. RapidArc is
capable of reproducing the high conformality achieved by conventional SBRT; dual
arc plans, delivering uniform dose distributions, yielded an average CI100% of
1.11 and D2cm maximum of 63% of the prescribed dose, compared to 1.33 and 77% (p-
values of .002 and .005, respectively) for conventional SBRT. Application of a
short, non-coplanar arc, in conjunction with dual coplanar arcs, improved sparing
of OARs in direct proximity of the PTV at the expense of treatment time. RapidArc
allows for faster treatment delivery; conventional SBRT delivery averages 13.7
minutes at our institution, whereas coplanar dual arcs are estimated to average
treatment durations of 4.2 minutes. CONCLUSIONS: RapidArc is capable of
generating conformai dose distributions and sparing of OARs, allows greater
freedom in plan optimization, and reduces treatment time significantly.
PMID- 28517220
TI - SU-E-T-389: Accuracy of a VMAT Planning System for Head and Neck Radiotherapy.
AB - PURPOSE: To determine the accuracy of VMAT treatment planning and delivery for
patients undergoing radiotherapy in the head and neck. METHOD AND MATERIALS: A
dosimetric study of a typical head and neck treatment plan has been carried out
using Chamber, film and TLD's placed inside an anthropomorphic phantom. Lateral
and AP port films were taken to verify the isocenter prior to treatment. Multiple
treatments were performed to assess the reproducibility and uncertainty in the
TLD measurements. Gafchromatic film was used between the phantom slices and then
analyzed as an independent check on the TLD results. The two data sets, from TLDs
and films, were then compared with the treatment planning system dose
calculations. RESULTS: The measured dose to the primary planning tumor volume
agrees with the planning system within 2%. The comparison of the measured dose to
the secondary tumor volume ranges from 3-6% and the spinal cord comparison ranges
from 3-10%. CONCLUSION: This new Smart Arc treatment, VMAT, has great benefits to
the patient in that patient motion and internal motion of the tumor is
dramatically reduced. Challenges arise in predicting the dose near
heterogeneities between the treatment planning system and actual measurement.
PMID- 28517221
TI - SU-E-T-400: SBRT Dose Verification Using Monte Carlo Simulation.
AB - PURPOSE: To verify the SBRT plans on CMS Xio treatment planning system using the
Monte Carlo simulation and investigate the related issues. METHODS: The SBRT
plans with 6 MV were created on CMS Xio treatment planning system with
superposition algorithm. The same patient's CT, beam geometry and MUs were used
in the Monte Carlo simulation (MC) on MCSIM. MCSIM is an EGS4-based MC dose
calculation system for photon and electron beams. The Monte Carlo plans were
compared with the Xio plans to verify Xio superposition algorithm for SBRT. The
electron disequilibrium was particularly investigated by comparing the DVHs for a
2-mm thick peel of the GTV. The beam energy was changed from 6 MV to 10 MV for MC
to test energy effect on SBRT dosimetry. RESULTS: Six SBRT lung plans created on
Xio and delivered on Varian 21 EX linac were included in this study. The tumor
GTV ranged from 1.4 cc to 11 cc and the dose ranged from 1950 cGy to 5400 cGy.
The comparisons were made in terms of DVHs, mean doses, minimal doses, and
maximal doses for GTV. The results showed all the dose values of Xio plans agreed
with MC to within 2% with only two exceptions of 3% and 5%. The dose distribution
in the peel of GTV followed the same pattern as the whole GTV. This indicated the
Xio superposition algorithm has well accounted for electron disequilibrium. The
10-MV beams had both hot and cold spots from DVH comparison. This may be due to
the large build-up region for high energy beams. CONCLUSIONS: The Xio
superposition algorithm has adequately accounted for electron disequilibrium and
can perform accurate dose calculation for SBRT. Compared to high energy beams, 6
MV is preferable in terms of the GTV coverage and dose homogeneity.
PMID- 28517222
TI - SU-E-T-421: 6MV Radiation Small Field Dose: Off Axis and Penumbra Effects, a
Study with Radiochromic Film.
AB - PURPOSE: To accurately determine relative dose factor scaling, tissue depth
relation, and penumbra details of small 6MV radiation fields with an emphasis on
far-off-central-axis fields for various MLC designs -subject matter important in
the context of SRS, FSRT, SBRT, and IMRT. METHODS: Radiochromic film designed for
quantitative dosimetry, EBT3TM film (Ashland Inc.) can be reliably used as a
relative dosimeter to within 1% accuracy if one controls for both film and
flatbed scanner variation. This enabled a study of the fine detail of small
radiation fields and the impact upon these small dose profiles by different MLC
designs both on central axis and off. In particular, the impact of leaf-end
penumbra from bifocal MLC Optifocus (Siemens) and Synergy Beam Modulator (Elekta)
is examined.EBT3 films were placed at 100cm SAD in solid water phantom and
irradiated to 200 MU at various depths 1.5cm - 20cm and for various off-axis
locations. The films were analysed to give the detailed dosimetric profile of
each small field and relate them to both a standard reference field (10 * 10)cm2
and to a broadfield flatness/symmetry irradiation (20 * 20)cm2 . Films were
scanned at ~20 hours post irradiation on an Epson 2000 flatbed scanner and
analysed using FilmQAPro and in-house methods. RESULTS: As small field size
decreases, the field center falls within the penumbra of each MLC edge for
megavoltage photon energies. The penumbral effects cause the conventional
dosimetric quantity SP to sharply depart from the smooth fieldsize dependence for
larger conventional fields. CONCLUSIONS: Careful characterization of small field
dose and leaf end modeling within a TPS is crucial in both predicting accurate
small field dosimetry and off-axis dosimetry.
PMID- 28517223
TI - SU-E-T-432: Comparison of HDR Treatment Plans for Interstitial Brachytherapy with
Intracavitary Savi Brachytherapy for Post Lumpectomy Breast Cancer.
AB - PURPOSE: To compare the dose distributions from HDR brachytherapy using
interstitial catheter implants and Intracavitary Savi applicator for breast
cancer patients following lumpectomy. METHODS: We have treated over 200 post
lumpectomy breast patients with brachytherapy and Savi applicator (Cianna
Medical) . The interstitial technique used a custom built template for placement
of catheters under the image guidance. The Savi applicator was placed into the
resected cavity and the applicator was expanded to cover the cavity under CT
image guidance. The criteria used for plan evaluation was prescription dose
covered 95 to 100% of the volume 1.5* prescribed dose to cover <30% of the PTV
and 2.0 * prescribed dose covered <10% of the PTV. The Savi plans were evaluated
with PTVeval to cover 90 to 95% of the prescribed dose and 1.5*PTVeval not to
exceed 50cc, 2*PTVeval to cover <10% of volume. RESULTS: The PTV for interstitial
ranged from 29 to 170cc, and that for Savi the PTVeval varied from 28 to 111. For
interstitial the 1.5* dose reference expressed as % of PTV varied from 11% to 30%
with a median at 24.9%. For Savi the 1.5* dose reference volume expressed as % of
PTVeval ranged from 30 to 50% with a median of 40%. The 2* dose reference covered
volume expressed as % of PTV varied from 5.5 to 30% of PTV at a median value of
8.5%. The same for Savi varied from 13 to 31% at a median value of 19.4%. The
skin dose for interstitial implant was less than 70% whereas same for Savi
application was <100%Conclusions: We conclude that the dose uniformity for V1.5
and V2 were better with interstitial implant as compared to Savi application.
Also the interstitial implant allowed covering the desired margin of resection
without restriction imposed due to air gap. Savi application, being less invasive
was better preference by the patient over interstitial.
PMID- 28517224
TI - SU-E-T-414: Clinical Implementation of Anthropomorphic Lung Phantom for Patient
Specific SAbR QA.
AB - PURPOSE: Dose calculations for lung stereotactic ablative radiotherapy (SAbR) are
challenged by the presence of extremely heterogeneous tissue and small treatment
volumes. In this work, an anthropomorphic chest phantom has been constructed for
the purpose of commissioning treatment planning systems (TPS) and for patient
specific SAbR QA. METHODS: A CT scan of a realistic chest phantom containing
tissue equivalent materials for the spine, ribs, and lungs was imported into a
Pinnacle TPS (CCC dose algorithm) where treatment plans were created for right
and left-sided lung lesions. The phantom lungs are unique in that they contain
embedded unit density spherical targets (2 and 4cm in diameter) that represent
lung lesions. Plans directed to both tumors were designed for PTVs ranging from 2
5cm in diameter using 6, 10, and 15MV beams while passing RTOG 0813 dose and
conformality criteria. Each plan was then exported to an Eclipse TPS (AAA dose
algorithm) for dose calculation. Plans were delivered with a TrueBeam LINAC
corrected for machine output. Point dose measurementswere verified with a 0.015
cc air ionization chamber placed in the center of each tumor. RESULTS: While the
majority of plans developed in Pinnacle passed conformality criteria, the dose
distribution as calculated in Eclipse failed to meet the RTOG guidelines,
particularly for the small tumor at higher photon energies. All point dose
measurements matched both TPS within 4%. Both TPS calculated a lower point dose
than measured for large PTVs at all energies, improving as PTV size decreased.
CONCLUSIONS: After comparing TPS and validating calculations with point dose
measurements, the phantom was clinically implemented for patient-specific
conformal SAbR QA.
PMID- 28517225
TI - SU-E-T-425: Impact of Model Based Dose Calculation Algorithm for Ir-192
Intracavitary Brachytherapy with Shielded Applicator.
AB - PURPOSE: To determine the impact of a grid based Boltzmann solver (GBBS) on a
cohort of cervical cancer patients treated with Ir-192 intracavitary
brachytherapy with shielded applicators. METHODS: Retrospective plans were
generated using BrachyVision v8.8 (TPS) with GBBS Acuros v1.3.1. The study
includes 24 patients that had CT planning images acquired with CT/MR compatible
applicators. Using the TPS applicator library, shielded colpostats and tandem
(#AL13122005) were virtually positioned to replace the applicators seen on CT.
Dwell weights were based on TG43 delivering 6 Gy to point A. Four GBBS
calculations were performed to assess differences from the standard of practice
TG43. The different GBBS calculations were: 1) no applicator modeled, body= 1
g/cc muscle, 2) applicator modeled, body=1g/cc muscle, 3) applicator modeled, CT
to-material mapping with contrast (vaginal packing, rectal, Foley balloon) =
1g/cc muscle, and 4) applicator model, CT-to-material mapping without material
overrides. The multiple GBBS calculations allow differences from TG43 to be
attributed to factors representing the modeling of source and patient boundaries
(scatter conditions), tissue heterogeneities, and applicators. RESULTS:
Differences between GBBS4 and TG43 at clinical dosimetric points were as follows:
[mean +/- standard (min, max)], Point A: - 2.5% +/- 0.5% (-3.8%, -1.2%), Point B:
-1.5% +/- 1.0% (-3.2%, 1.1%), ICRU rectum: -8.4% +/- 2.5% (-14.0%, -4.1%), D2cc
rectum: -6.2% +/- 2.6% (- 11.9%, -0.8%), ICRU bladder: -7.2% +/- 3.6% (-15.7%,
2.1%); D2cc bladder: -3.4% +/- 1.8% (-7.2%, -1.1%). Bar plots comparing the
modeling factors previously listed show that applicator modeling is the largest
contributor to differences from TG43. CONCLUSIONS: Clinically significant dose
differences (>5%) relative to TG43 exist when using a model-based dose
calculation algorithm such as the GBBS with shielded applicators. Differences
were largely due to applicator modeling, not tissue heterogeneities, source
modeling, or patient boundary modeling.
PMID- 28517226
TI - SU-E-T-391: Modelling Peripheral Photon Dose in TomoTherapy Treatments.
AB - PURPOSE: The delivery of the therapeutic radiation dose to the tumour in photon
radiotherapy, also implies dose deposition in distant organs (peripheral dose)
related to secondary cancers induction (Hall and Wuu, Int J Radiat Oncol Biol
Phys 56:83-88, 2003). Therefore, peripheral dose estimation in MU-demanding
techniques, such as Helical TomoTherapy (HT), becomes relevant. TLD measurements
and Monte Carlo modelling were compared by D'Agostino (Strahlenther Onkol
187:693, 2011). The purpose of this work was to find out experimental models
predicting the equivalent photon dose as a function of the distance to the
isocenter for different treatment types. The prostate case is presented here.
METHODS: A HT prostate plan was delivered to an anthropomorphic phantom mimicking
a male adult. The phantom was made of polyethylene blocks whereas light wood was
used for lungs. 16 points distributed along the phantom, covering different
depths, were selected (SA!nchez-Doblado IFMBE, World Congress Med Phys & Biomed
Eng, 259-261, 2009). Additionally, a polyethylene sheet was inserted in the
phantom to measure the off-axis dose profile at midplane depth. Measurements were
carried out with standard TLD-100 pairs of dosimeters (calibrated in a 137Cs
source). RESULTS: Two-exponential-terms curve fitting was carried out to model
separately the scatter and leakage contribution (f=a*exp(-b*x)+c*exp(-d*x)). The
former resulted predominant in the proximal region (10=x=14cm) and the latter in
the distal re gion (x=14cm). Both components equate at 18cm. Scatter contribution
becomes negligible for x=23cm. Points at 5cm were not used for the model as they
are too close to the isocenter to be considered as peripheral dose. Model fits
well experimental data (13% mean deviation). Only depths behind the build-up
region could be properly modelled. CONCLUSIONS: Peripheral photon dose profiles
in HT treatments have been modelled by a two-exponential-terms curve modelling
separately scatter and leakage.
PMID- 28517227
TI - SU-E-T-436: Feasibility of Using the 'Irregular Surface Compensator' Planning
Feature of the Eclipse TPS for Total Body Irradiation (TBI) Treatment Planning.
AB - PURPOSE: To investigate the feasibility of using the Irregular Surface
Compensator (ISC) planning feature of the Eclipse treatment planning system (TPS)
for Total Body Irradiation (TBI). METHODS: TBI treatments require that the whole
body receives within +-10% of the prescribed dose. Different body parts with
different thicknesses compared to the umbilicus separation may receive higher or
lower doses compared to the prescribed dose. Another challenge is to keep the
lung dose below 10Gy to avoid complications. To mitigate this problem, physical
compensators and blocks are used during the treatment for different body parts
and lungs. This method presents a challenge during the treatment delivery and
prolongs the treatment time due to patient setup, in-vivo on-line dosimetric
monitoring and the adjustment of the compensators frequently during the
treatment. We investigated the use of ISC planning feature of Eclipse TPS which
is an electronic compensation method that calculates a fluence map based on the
body contour from the CT image. The fluence map is delivered with dynamic MLCs .
This TBI treatment technique was tested using a Rando phantom in Head First
Supine position with lateral beams at SSD=250cm.The calculated fluence were
edited so that the lung received <~10Gy for 12Gy prescription. A single fraction
of 2Gy was delivered and the in-vivo measurements were performed in the neck,
lung and the umbilicus by using OSLDs. RESULTS: OSLD measurements and the Eclipse
TPS predictionswere 200.4/195.0, 162.2/168.9, and 196.1/208.9 cGy for the neck,
lung and the umbilicus respectively. CONCLUSIONS: The feasibility of using the
'Irregular Surface Compensator' feature of Eclipse TPS for TBI treatment planning
was demonstrated. Good agreement (<6%) between the predicted and measured doses
was obtained. The proposed planning and delivery simplifies the compensation and
blocking to achieve uniform dose distributions and reduces the treatment time.
PMID- 28517228
TI - SU-E-T-402: Coordinate Transformation after Stereotactic Frame Reapplication in
Gamma Knife Radiosurgery.
AB - PURPOSE: In Gamma Knife (GK) radiosurgery, the occurrence of reapplying the
stereotactic frame due to collision with the collimator leads to re- examination
and re-planning. For the treatment of vascular lesions, it is a burden not only
to physicians but also to patients to get invasive angiography procedure again.
To avoid undergoing second angiography examination, and reduce re-planning time,
a mathematical coordinate transformation method using the stereotactic images has
been developed. METHODS: The MR or CT images of a patient brain before and after
frame reapplication can be correlated with each other using the Affine
transformation. The transformation parameters which minimize the RMS error of the
original and transformed coordinates between the images were determined using a
genetic algorithm. Three CT image studies of skull phantom were used for the
verification of the algorithm. Moreover, five MR image studies of patients who
underwent more than one GK procedure were used for the clinical evaluation. The
coordinates under the original treatment plan were converted to new coordinates
using the transformation matrix, and their dosimetric outcomes were compared.
RESULTS: The RMS error in the coordinate transformation of skull phantom and
clinical images was 0.3 mm and 0.6 mm, respectively. For total 9 treatment
lesions of 0.2 ~14.1 cc, 3% and 11% RMS error in the irradiation time and target
coverage were found respectively. The patients with only translational movement
during the frame reapplication showed similar plan conversion results with the
original plan. Also, deeply-located lesions showed a better RMS error of 3% in
the conformity index than superficial lesions close to the skull. CONCLUSIONS:
New treatment plans were obtained by applying the coordinate transformation to
the original plans after the frame reapplication. The converted plans maintained
the quality of the original plans with a little change in dose distribution
arising from head rotation. This work was supported by a grant no. 04-2011
0320110130 from the Seoul National University Hospital Research Fund and a
National Research Foundation of Korea (NRFK) grant funded by the Korean
government (MEST) (Grant No. K20901000001-09E0100-00110).
PMID- 28517229
TI - SU-E-T-418: Evaluation of Peripheral Dose for SRS Treatment Radiations with the
VIS CyberKnife: A Phantom Study.
AB - PURPOSE: Stereotactic radiosurgery (SRS) procedures are known to deliver a very
high dose per fraction and thus, the increased risk of secondary types of cancer
due to increased peripheral dose could be a limiting factor for the long term
survival of the patients. The aim of this study is to evaluate the peripheral
dose (PD) received at preselected anatomical sites in an anthropomorphic phantom
for treatments of intracranial lesions with the CyberRnife. METHODS: Eight
patients treated using the CyberRnife were selected for this study. Organs at
risk and target were delineated on volumetric CT data and treatment planning
(Multiplan v.4.5.0) was optimized accordingly, in order to achieve the required
prescribed target dose and critical structures sparing for each patient. The
final treatment plan was delivered with a CyberRnife VIS (Accuray, Inc.,
Sunnyvale, CA) operating with a dose rate of 1000 MU/min at a flattening filter
free mode and upgraded shielding. We performed our measurements using a male
anthropomorphic RANDO phantom (Alderson Research Laboratories, Inc., Stamford,
CT). Groups of three TLD 100 were placed anteriorly inside RANDO at a depth of 5
cm at locations corresponding to the thyroid, breast or lung, uterus and inferior
abdomen for each treatment plan. RESULTS: The average percentage dose normalized
to the prescribed dose for the thyroid gland was 0.92+0.23 % with a max of 1.95%.
The maximum reduction of the PD (expressed as percentage of the prescribed dose)
was 80% between the thyroid gland and the lower pelvic area. Similarly the PD
normalized to the number of MU showed an average of 0.84*10-3 (cGy/MU), with a
max of 0.0025 (cGy/MU) for the thyroid gland region. CONCLUSIONS: It is evident
that the PD is proportional to the number of MU as well as to the prescribed
dose. These correlations can be utilized to estimate the PD during intracranial
treatments.
PMID- 28517230
TI - SU-E-T-429: Image-Guided Eye Plaque Brachytherapy Optimization: Implications for
Patients at 2-Year Follow-up.
AB - PURPOSE: Episcleral eye plaque brachytherapy has been utilized in the treatment
of intra-ocular malignancies, delivering large prescription doses to the apex of
the tumor. Advances in dose calculation and image guidance, via calibrated fundus
images, enable localization of the tumor and determination of dose to the macula,
optic disc, and lens. A two-year post-implant study aims to correlate dosimetry
with local tumor control and changes in visual acuity, as well as assess the need
for plaque optimization with respect to critical structures. METHODS: A
retrospective, two-year follow-up study of 21 patients who have received
episcleral eye plaque brachytherapy at our institution was used to correlate
dosimetry with clinical outcomes and evaluate the need for eye plaque
optimization. BEBIG Plaque Simulator wasused in treatment planning; fundus
photographs were registered for tumor localization and the TG43-U1 formulism
enabled dose calculation of I-125- loaded COMS plaques. Doses to the apex,
macula, and optic disc were correlated to changes in apex height and visual
acuity. Selected patients were replanned using optimization strategies to reduce
dose to critical structures. RESULTS: A total of seven patients (33%) noted
improved eyesight at two years. 11 (52%) patients lost at least two lines of
vision at two years. Two patients saw increases in apical height (9%) within two
years. Optimized eye plaque plans were able to reduce optic disc and macular
doses (average 68Gy and 80Gy, respectively) by 36% and 25% on the average, while
maintaining the prescribed dose. CONCLUSION: Image guidance and optimization are
important tools that can aid in treatment of intra-ocular malignancies, as these
techniques provide physicists with the ability to spare critical structures while
delivering the prescription dose, thus increasing the possibility of local
control and vision sparing.
PMID- 28517232
TI - SU-E-T-440: Dosimetry Parameter Comparison between Field-In-Field Technique and
Conventional Physical Wedge Technique for Whole Breast Radiation Treatment.
AB - PURPOSE: To compare an advantage/disadvantage between Field-in-Field (FIF)
technique and conventional physical wedge (PW) technique for a whole breast (WB)
tangential field irradiation. METHODS AND MATERIALS: Total 86 patients were
included in this study. 46 of them were left breast cancer cases. FIF/PW plans
were created by Eclipse (V7.3, Varian) with 6MV or 6MV mixed with 18MV. Plans had
a same ioscenter location, beam setup and normalized isodose line selection for
each case. Varian 21EX Linac with 120 MLC was used for beam delivery. Two plans
were compared by PTV encompassed by 95% isodose line (V95), dose inhomogeneity
(DI), dose received by 10% volume of lung (D10), mean lung dose (MLD), dose
received by 5% volume of heart (D5), Mean heart dose (MHD), total MU, maximum
dose in the plan and the number of field needed for each fraction. RESULTS:
Comparing with PW plan, FIF plan showed an average percentage improvement of V95
was 0.1+/-1.6, DI was 0.6+/-5.0, MLD was 1.5+/-4.2, D5 was 2.0+/-8.8, MHD was
3.2+/-4.6. However, D10 increased by 1.4%+/-0.050. FIF lowered an average daily
MU by 28.5%+/-0.080, maximum dose by 0.5%+/-0.018, and increased number of
treatment field by 1.50+/-0.356. There were 12 cases treated with mixed beam in
PW technique vs 10 in FIF technique. CONCLUSION: The advantages of FIF technique
included: (1) Reduce radiation contamination to contra lateral breast and Linac
room induced activity by remove the PW, lower MU and diminish a higher energy.
(2) Time saving was not only from less MU but also from not need go into the
treatment room for a wedge adjustment. (3) Reduced the therapist work load. (4)
Regular MU 2nd check was applied because there was not FIF merge involved in the
treatment field. With a MLC to shape the field and treatment record/verification
system to control the treatment, increasing number of treatment field didn't show
as a problem.
PMID- 28517231
TI - SU-E-T-395: Achievability and Optimization of Synchrotron-Based Respiratory Gated
Spot Scanning Proton Beam Delivery.
AB - PURPOSE: The purpose was to investigate the interplay of residual motion in
realistically delivered respiratory gated spot scanning proton beam by a
synchrotron. METHODS: A MatriXX 2D ion-chamber array detector was placed on a
moving platform. The platform with the 2D ion-chamber array detector was moved
based on sin4 motion with 3s and 5s cycle and 20 mm amplitude. Its motion was
monitored by a laser displacement sensor (ZS-LDS2VT, omron, Japan). The
respiration gate threshold level was set at 30% duty cycle and the residual
motion within the gate window was approximately 6 mm. A 10*10 cm2 uniform field
was delivered by a matrix of 13*13 spots with ~ 8 mm spot size (s) and 8 mm spot
spacing. Measurements were done for the field delivered with a single painting
and multiple re-painting, from 2 to 12 times, for both orthogonal and parallel
scan directions. The same field was also measured without moving the detector,
defined as the static reference dose. Dose homogeneity was compared between with
gated and the static dose distributions. RESULTS: The worst single painting
result of the dose homogeneity ratio was 0.90 in 3s motion cycle and 0.93 in 5s
motion cycle with the orthogonal scan pattern, and 0.97 in 3s and 0.98 in 5s
motion with the parallel scan pattern, respectively . The homogeneity ratio
improved to over 0.98 by 4~6 times repainting in orthogonal and only 2 times re
painting with the parallel scan. CONCLUSIONS: The respiratory gated spot scanning
proton beam delivery is sensitive to spot movement direction relative to the
residual motion of the target. A proper selection of the number of repainting and
the scan direction can improve beam delivery quality. The study offers a basic
understanding when implementing respiratory gated spot scanning proton beam
treatment.
PMID- 28517233
TI - SU-E-T-406: Online Image-Guidance for Prostate SBRT: Dosimetric Benefits and
Margin Analysis.
AB - PURPOSE: To evaluate the dosimetric benefits of online image guidance during
prostate stereotactic body radiotherapy (SBRT) and the potential on margin
reduction. METHODS: 28 prostate SBRT patients were retrospectively studied, each
treated with 37Gy in 5 fractions. RTOG recently opened a similar protocol (0938).
During treatments, per-beam couch corrections were made based on the actual
target motion provided by dynamic tracking with either Calypso or per-beam OBI
imaging. Dosimetric benefits of online correction were evaluated by comparing
delivered dose distributions with and without such correction. The dose
distribution without correction was generated in the same treatment planning
system by accumulating doses without online correction from the each beam and
each fraction. Quantitative analyses include the dosimetric difference between
delivered doses with and without correction; the correction magnitude and
frequency; and the potential on margin reduction based on the margin recipe by
Van Herk et al. RESULTS: (1) Delivery without online correction results in small
reduction on target mean dose (0.03+/-0.05Gy), maximal dose (0.01+/-0.06Gy), and
conformity index (<0.06). (2) Delivery without online correction has small impact
on OAR dose: 26 out of 28 patients have <1%/1.5cc differences in
V18.5Gy/V24Gy/V28Gy/V33Gy/V37Gy for both the bladder and the rectum. Maximal
differences are 4cc of the bladder and 1.6cc of the rectum in mid-dose regions
(V18.5Gy). (3) For femoral heads, <1cc/1Gy differences are observed in
V20Gy/Dmean/D1cc.(4) Average number of couch corrections per fraction is 0.49.
The magnitudes are: (-0.2+/-2)mm vertically, (-0.1+/-2.1)mm longitudinally, and (
0.2+/-1.4)mm laterally. (5) Margin determined by actual target motion in this
patient population is 2.5mm isotropic. CONCLUSION: For both target coverage and
OAR sparing, overall small benefit is seen from per-beam couch correction under
dynamic tracking. The target motion between beams is small and random, and
indicates a population-based margin size of 2.5mm.
PMID- 28517234
TI - SU-E-T-388: Verification of Monitor Units and Dose Distributions in IMRT Plans
Using Monte Carlo Algorithms on the E-IMRT Web Platform.
AB - PURPOSE: Currently, quality control (QC) for each IMRT treatment is performed by
dose distribution measurements. These techniques are very time-consuming and
require long accelerator downtime. QC could be only based in verification of
monitor units and dose distributions, if precise control of MLC is carried out.
In such a manner, the e-IMRT platform (http://eimrt.cesga.es/) is a remote
distributed computing tool, which allows comparison between the dose
distributions calculated by a TPS and those calculated by Monte Carlo (MC).
METHODS: Previously, our linear accelerator (Oncor Impression, Siemens) was
commissioned. For this purpose, comparison of experimental and MC simulated data
was carried out. Several IMRT treatments plans were calculated in superposition
algorithm (TPS Xio(r)CMS 4.60.00) and used as input data for the e-IMRT platform.
These treatment plans were previously verified employing a 2D array MapCheckTM,
Sun Nuclear. The gamma index (3%, 3mm) was used for validating results. RESULTS:
The platform displays calculated doses using MC, also gamma map (in the CT
images, not only statistical data) and histogram shown in Figures 1a), b) and d).
The gamma map illustrates the differences between the input and calculated doses.
According to the legend in Figure 1 d), these differences correspond to less than
1%. Results show good agreement between the doses calculated by TPS and those
computed by e-IMRT platform. CONCLUSIONS: If a rigorous quality control is
established for MLC and optimisation criteria (number of gantry angles, minimum
segment size, levels of intensity for fluency map) are used. Then, QC for IMRT
standard treatment plans would be only based on the verification of monitor units
and dose distributions using e-IMRT II.This work has been funded by the Xunta de
Galicia, Project R&D Grant 09SIN007CT. We would like to thank Centro de
SupercomputaciA3 n de Galicia for the computational resources and support.
PMID- 28517235
TI - New psychoactive substances: Purchasing and supply patterns in Australia.
AB - OBJECTIVE: To examine the purchasing and supply patterns of new psychoactive
substance (NPS) consumers in Australia. METHOD: Data were obtained from a self
selected sample of 296 past-year NPS consumers, with comparisons made across
dimethyltryptamine (n = 104), 2C-x (n = 59), NBOMe (n = 27), and synthetic
cannabinoid (n = 22) users. RESULTS: Most consumers (58%) nominated a friend as
their main NPS source, and almost half (46%) reported that they had supplied NPS
to others in the past year (predominantly "social supply"). However, when
comparisons were made across NPS, NBOMe users were more likely to nominate a
dealer (30%) or online marketplace (22%) as their main source and to report:
supplying NPS to others (63%); supplying to strangers (29%) and acquaintances
(24%); and supplying NPS for cash profit (29%). Similarly, NPS consumers who
nominated online markets as their main NPS source (9%; n = 26) were more likely
to have supplied NPS to others (risk ratio [RR] 1.57); supplied to strangers (RR
6.05) and acquaintances (RR 12.11); sold NPS for cash profit (RR 4.36); and to
have exchanged NPS for something else (RR 3.27) than those who reported
alternative primary sources. CONCLUSION: NBOMe consumers and those who nominated
online markets as their main NPS source reported greater engagement with for
profit supply; it is unclear if these individuals have "drifted" into dealing or
if they were already engaged in such activities.
PMID- 28517236
TI - Effect of centralization on long-term survival after resection of pancreatic
ductal adenocarcinoma.
AB - BACKGROUND: Centralization of pancreatic surgery has resulted in improved short
term outcomes in a number of healthcare systems. The aim of this study was to see
whether hospital volume influenced long-term prognosis, use of adjuvant therapy
or histopathological evaluation of patients undergoing surgical resection for
pancreatic ductal adenocarcinoma (PDAC). METHODS: Patients undergoing surgical
resection of PDAC in Finland between 2002 and 2008 were identified from national
registers. Demographic, histopathological, operative and oncological data were
recorded, and the histopathological slides of patients who survived for more than
4 years were reviewed. Operative volume was defined according to the annual rate
of pancreatoduodenectomy as: high-volume centres (HVCs; 20 or more resections per
year), medium-volume centres (MVCs; 6-19 resection annually) and low-volume
centres (LVCs; 5 or fewer resections annually). RESULTS: Some 467 patients who
had undergone resectional surgery for PDAC at 22 centres were included. Patient
demographics and resection types did not differ between centres. Thirty- and 90
day mortality rates were significantly lower in HVCs compared with LVCs: 0 versus
5.5 per cent (P = 0.001) and 2.5 versus 11.0 per cent (P = 0.003) respectively.
Tumours in HVCs were generally at a more advanced stage than those in LVCs (stage
IIB: 65.7 versus 40.6 per cent respectively; P < 0.001), but with no greater use
of adjuvant therapy. Significantly more patients survived for 2 years (43.3
versus 29.7 per cent; P = 0.034) and 3 years (25.4 versus 14.1 per cent; P =
0.045) after surgery in HVCs than in LVCs. More information was missing in the
histopathological reports from LVCs and MVCs than in those from HVCs (P <=
0.002). CONCLUSION: Both short- and long-term survival was significantly better
for patients operated on in HVCs. Histopathological analysis appears to be more
comprehensive in HVCs.
PMID- 28517237
TI - Development of an alginate hydrogel to deliver aqueous bait for pest ant
management.
AB - BACKGROUND: Insecticide sprays used for ant control cause environmental
contamination. Liquid bait is a safe and effective alternative, but it requires
bait stations to dispense the toxicant. We developed a biodegradable hydrogel to
deliver liquid bait obviating the need for bait stations. RESULTS: Alginate
hydrogel beads with preferred rigidity and maximum hydration in 25% sucrose
solution were engineered by optimizing a crosslinking process. The moisture
content of the substrate on which the beads were placed and the relative
atmospheric humidity significantly influenced water loss dynamics of the hydrated
hydrogel beads. Laboratory choice studies indicated that hydrated hydrogel beads
had reduced palatability to foraging ants when they lost >=50% water. An enzyme
linked immunosorbent assay (ELISA) indicated that the insecticide thiamethoxam
added to sucrose solution was absorbed into the hydrogel beads. Hydrogel beads
conditioned in sucrose solution with 1 mg L-1 thiamethoxam provided complete
control of all castes of Argentine ant Linepithema humile (Mayr) colony by 14
days post treatment in the laboratory trial and provided a 79% reduction in ant
activity after 8 weeks in the field trial. CONCLUSION: Alginate hydrogel beads
provided an effective delivery system for liquid baits laced with low
concentrations of insecticide to control Argentine ants. (c) 2017 Society of
Chemical Industry.
PMID- 28517238
TI - FleN and FleQ play a synergistic role in regulating lapA and bcs operons in
Pseudomonas putida KT2440.
AB - FleN generally functions as an antagonist of FleQ in regulating flagellar genes
and biofilm matrix related genes in Pseudomonas aeruginosa. Here, we found that
in Pseudomonas putida KT2440, FleN and FleQ play a synergistic role in regulating
two biofilm matrix coding operons, lapA and bcs. FleN deletion decreased the
transcription of lapA and increased the transcription of bcs operon, and the same
trend was observed in fleQ deletion mutant before. In vitro experiments showed
that FleN promoted the binding of FleQ to the lapA/bcs promoter DNA especially in
the presence of ATP. Both phenotype observation and transcription analysis showed
that, similar to fleQ deletion, fleN deletion significantly weaken the effect of
high c-di-GMP level on biofilm formation, surface winkle phenotype and expression
of lapA and bcs operons. Mutagenesis of the putative ATP binding motif in
FleNK21Q revealed that FleN ATPase activity played an essential role in the
regulation of flagellar number and swimming motility but was not critical for
biofilm formation. Our results revealed that FleN was not an antagonist of FleQ
but a synergistic factor of FleQ in regulating the two biofilm matrix coding
operons in P. putida KT2440.
PMID- 28517239
TI - The dose-effect relationship of baclofen in alcohol dependence: A 1-year cohort
study.
AB - OBJECTIVE: Our aim is to study the relationship between dose of baclofen and
effectiveness in alcohol dependence. METHODS: Two hundred two patients with
alcohol dependence, who received baclofen treatment for drinking reduction, were
followed up for 1 year. For each patient-month of treatment, the maximum daily
dose of baclofen (DDB) and average weekly alcohol consumption (AWAC) were
calculated. We defined a favorable drinking outcome as an AWAC under 200 g/w for
at least 2 consecutive months. We divided the DDB of each patient-month into 3
categories (low dose: <90 mg/d, medium dose: 90-150 mg/d, and high dose: >150
mg/d) and investigated the relationship between reaching a favorable outcome and
the concurrent DDB category in a time-varying Cox regression analysis. Hazard
ratios (HRs) were adjusted based on age, sex, and initial AWAC. RESULTS: One
hundred forty subjects were followed during at least 1 month. Of these patients,
58 (41%) had a favorable drinking outcome. In comparison to low dose, medium dose
was associated with a decreased rate of favorable drinking outcome (HR = 0.42;
95% CI [0.20, 0.88]), whereas no difference was found with high dose (HR = 1.31;
95% CI [0.65, 2.64]). CONCLUSION: The relationship between dose of baclofen and
favorable drinking outcome was U-shaped, that is, was increased at low and high
doses compared to medium doses.
PMID- 28517240
TI - Imaging after treatment in uterine malignancies: Spectrum of normal findings and
most common complications.
AB - Uterine malignancies account for the majority of gynaecologic cancers. Different
treatment options are available depending on histology, disease grade and stage.
Hysterectomy is the most frequent surgical procedure. Chemotherapy and radiation
therapy (CRT) represents the preferred therapeutic choice for locally advanced
uterine and cervical malignancies. Imaging of the female pelvis following these
treatments is particularly challenging due to alteration of the normal anatomy.
Radiologists should be familiar with both the expected post-treatment imaging
findings and the imaging features of possible complications to make the correct
interpretation and avoid possible pitfalls. The purpose of this review is to show
the expected computed tomography (CT) and Magnetic Resonance Imaging (MRI)
appearances of the female pelvis following surgery and CRT for uterine and
cervical cancer, to illustrate the imaging findings of early and delayed most
common complications after surgery and CRT, describing the suitable imaging
modalities and protocols for evaluation of patients treated for gynaecologic
malignancies.
PMID- 28517241
TI - Dopant-Free Hole-Transport Materials Based on Methoxytriphenylamine-Substituted
Indacenodithienothiophene for Solution-Processed Perovskite Solar Cells.
AB - Solution-processed hole transporting materials (HTMs) that are dopant-free show
promise for use in low-cost, high-performance perovskite solar cells (PSCs). The
highest-efficiency PSCs use organic HTMs, many of which have low mobilities and
therefore require doping, which lowers the device stability. Additionally, these
materials are not easily scaled because they often require complicated synthesis.
Two new HTMs (IDT-TPA and IDTT-TPA) were synthesized, which contained either an
extended fused-ring indacenodithiophene (IDT) or indacenodithienothiophene (IDTT)
core and strong electron-donating methoxytriphenylamine (TPA) groups as the end
capping units. The extended conjugation in the backbone of IDTT-TPA resulted in
stronger pi-pi interactions (3.321 A) and a higher hole mobility of 6.46*10-4
cm2 V-1 s-1 when compared with that of IDT-TPA (9.53*10-5 cm2 V-1 s-1 ). A
dopant-free, planar PSC that contained IDTT-TPA was fabricated and exhibited a
high power conversion efficiency (PCE) of 15.7 %. This cell exhibited a higher
PCE and less hysteresis than devices that contained IDT-TPA.
PMID- 28517243
TI - Sarcopenia is a risk factor for falling in independently living Japanese older
adults: A 2-year prospective cohort study of the GAINA study.
AB - AIM: The purpose of the present study was to investigate whether sarcopenia was
associated with future falls in the general Japanese older population. METHODS:
This study was a 2-year prospective observational study. Participants were
recruited from individuals who had an annual town-sponsored medical check-up and
had not received nursing care. The inclusion criteria for participants in our
study were: (i) agreement to participate; (ii) living independently; and (iii)
the ability to walk to where the survey was carried out and to provide self
reported data. A total of 223 residents (82 men, 141 women) participated in the
baseline assessment in the study. Demographic information, previous fall history,
locomotive syndrome, body function and structural measurements and pain at the
knee and/or lumber spine were assessed. The Asian Working Group for Sarcopenia
algorithm was used to classify the presence of sarcopenia, and assess the history
of falling when the participant received their annual medical check-up. RESULTS:
A total of 162 participants had an annual follow-up assessment, 50 of whom
(30.8%) fell at least once during the 2-year observational period after baseline
assessment. Previous falling history, prevalence of locomotive syndrome,
sarcopenia and pain were significantly higher in participants who had fallen
compared with participants who had not. Multiple logistic regression analysis
showed the prevalence of sarcopenia was a significant predictor of falling.
CONCLUSION: The key finding of the present study suggests that sarcopenia is a
risk factor for falling in older adults who are living independently even after
adjustment for previous falls and confounding factors. Geriatr Gerontol Int 2017;
17: 2124-2130.
PMID- 28517242
TI - Race/ethnicity is associated with ABO-nonidentical liver transplantation in the
United States.
AB - United Network for Organ Sharing (UNOS) policies allow for ABO-nonidentical liver
transplantation (LT) in candidates with Model for End-Stage Liver Disease (MELD)
scores greater than 30. Previous studies showed ABO-nonidentical LT resulted in
an 18% and 55% net gain in livers for B and AB candidates. These results
suggested that the current liver ABO allocation policies may need refinement.
There are, however, strong associations between ABO blood groups and
race/ethnicity. We hypothesized that race/ethnicity is associated with ABO
nonidentical LT and that this is primarily influenced by recipient ABO status. We
examined non-status 1 adult candidates registered between July 1, 2013, and
December 31, 2015. There were 27 835 candidates (70% non-Hispanic White, 15%
Hispanic, 9% Black, 4% Asian, 1% Other/Multiracial). A total of 11 369 underwent
deceased donor LT: 93% ABO identical, 6% ABO compatible, and 1% ABO incompatible.
Black and Asian race/ethnicity were associated with increased likelihoods of ABO
nonidentical LT. Adjustment for disease etiology, listing MELD, transplant center
volume, and UNOS region did not alter this association. Stepwise inclusion of
recipient ABO status did eliminate this significant association of race/ethnicity
with ABO-nonidentical LT. Blacks and Asians may be advantaged by ABO-nonidentical
LT, and we suspect that changes to the existing policies may disproportionately
impact these groups.
PMID- 28517245
TI - SU-E-T-312: Optically Stimulated Luminescent Dosimeter Performance in High Dose
Rate Brachytherapy.
AB - PURPOSE: To investigate the use of optically stimulated luminescent dosimeters
(OSLDs) for high dose rate (HDR) Ir-192 brachytherapy. While common in
megavoltage radiotherapy applications, the performance of OSLDs using kilovoltage
energies, high dose gradient and high dose rate regions ubiquitous to HDR has not
been demonstrated. METHODS: Commercially available nanoDotTM (Landauer, Glenwood,
IL) OSLDs - 5mm diameter and 0.2mm thickness - were irradiated using an Ir-192
source in various geometries to determine dose rate dependence. Angular
geometries were created using a circular applicator designed for accelerated
partial breast irradiation by Accuboost(r). RESULTS: Response remained linear for
high doses and was independent of dose rate. Specifically, the OSLDs were shown
to be linear with dose up to 200 cGy then became slightly supra-linear up to 600
cGy. There was a slight angular dependence for OSLDs which becomes significant in
'edge-on' scenarios. An asymmetry in this angular dependence was discovered, but
was attributed to cable curvature, point source approximation, and positioning
within its plastic casing. CONCLUSIONS: Clinical HDR doses of 300 cGy fall within
the linear, dose-rate-independent region. Angular independence can be maintained
by avoiding extreme 'edge-on' measurement geometries. Because of re- readability,
OSLDs can serve as a permanent record or alternatively be annealed within a few
hours using conventional fluorescent light. Lastly, OSLDs are produced for only
$5 each. Due to these features, in conjunction with the dosimetric performance,
OSLDs should be considered a reliable tool for in vivo HDR brachytherapy
measurements.
PMID- 28517244
TI - SU-E-T-290: Dosimetric Verification of Helical Tomotherapy against Experimental
Measurements for Head and Neck Treatments.
AB - PURPOSE: To verify a Tomotherapy plan for a typical head and neck treatment
against experimental measurements. METHODS: The treatment plan for a head and
neck case was generated by the Tomotherapy treatment planning system (TPS) to
deliver ~70 Gy in 33 sessions to the contoured PTV. The plan was calculated on a
CIRS ATOM anthropomorphic phantom that provides a grid spacing of 3*3 cm2 holes
to accommodate thermoluminescent detectors (TLD). The plan was verified against
experimental measurements carried out by 7 LiF:Mg,Ti (TLD-700) TLD. Up to 20
locations were selected within the irradiated region and three detectors were
used simultaneously at each point to decrease the statistical uncertainty. TLD
locations were labeled in the planning system and dose comparisons between TPS
prediction and experimental measurements were performed in terms of absolute dose
to water for a single fraction. We examined the dose from (i) the corresponding
3.5MV Tomo-scan alone and (ii) the complete treatment. TLD-700 were found to
fulfill the requirements of reproducibility, linearity and flat energy response
in a previous study. In particular, TLD energy response was previously checked
for 6 MV flattening filter free and conventional radiation beams under reference
conditions. RESULTS: Doses derived from the TPS were in most cases in good
agreement (4% on average) with TLD dose measurements within TLD statistical
uncertainties (about 3%). Larger discrepancies up to 7% were found for points
close to complex tissue inhomogeneities, such as bony structures. Dose from the
scanning procedure alone is about 1 % of the dose per fraction. CONCLUSIONS: This
work indicates that dose delivery plans created with Tomotherapy TPS are accurate
for head and neck tumor localizations.
PMID- 28517246
TI - SU-E-T-295: Factors Affecting Accuracy in Proton Therapy.
AB - PURPOSE: To examine the various processes involved and to assess their effects on
the accuracy in proton therapy. METHODS: Proton therapy involved several
processes: (1) Beam commissioning. (2) CT scan of patient. (3) Contouring. (4)
Treatment planning. (5) Output factor measurements for each field. (6) Patient
setup verification with image guidance. (7) Dose delivery. (8) Neutron dose and
proton RBE at the distal edge. Within each step, there are several sub-processes
that each may contribute to the uncertainty in the treatment. By analyzing each
of the subprocesseswithin each process, based on measurements or published data,
we estimated a % uncertainty to each sub-process and/or a distance uncertainty
(in millimeter) on the proton range. A total uncertainty in proton therapy is
estimated. RESULTS: The uncertainties assessed for the various processes are :
(1) +/-1.5%; (4) +/-3.0%, and 1-3mm; (5) +/-2.0%; (6) +/-2 mm; (7) +/-2.0%, +/
2mm. The uncertainties in (2) CT, (3) contouring and neutron dose in (8) strongly
depend on the location and type of the tumor. On the other hand, the proton RBE
at the distal edge in (9) is still debatable and may affect the dose uncertainty
from 0-20% depending on which value we want to accept. Thus the overall
uncertainty in proton therapy is at least +/-4.5% and +/-4 mm (by adding the
various uncertainties in quadrature), without consideration of processes (2), (3)
and (8), and the RBE effect. CONCLUSIONS: Due to the complexity in proton therapy
and the various factors that may affect the accuracy in proton therapy, it is far
more complicated to assess the accuracy in proton therapy. Our preliminary study
showed that the accuracy in proton therapy is at least +/- 4.5% in dose delivered
to a tumor with an uncertainty of +/-4mm to the distal edge of the SOBP.
PMID- 28517247
TI - SU-E-T-315: Planning and Verification of CT-Based HDR Intraluminal Brachytherapy
Treatment for Malignant Obstructive Jaundice.
AB - PURPOSE: To present our experience using CT to plan and verify intraluminal HDR
treatment for a patient with obstructive jaundice. Due to the obstruction's
proximity to the small bowel, along with small bowel adhesions from past surgical
history, it was imperative to verify source position relative to the bowel before
each treatment. METHODS: Treatment was administered to a total dose of 2000cGy in
5 fractions via a 6F intraluminal catheter inserted into the patient's 14F
percutaneous drainage catheter. Graduations on the intraluminal catheter were
used to measure the exact length of catheter inserted in to the patient's
drainage tube allowing reproducibility. Dummy seeds inserted during CT were
identified by iteratively aligning the planning system's 3D reconstruction axis
to the catheter at multiple points as it snaked through the liver. Taking in to
account the known offset between actual dwell positions and dummy source
positions, we determined what dwell positions to activate for planning. CT
verification was performed prior to each treatment to insure that the drainage
catheter had not moved and that the distance from treatment site to small bowel
was adequate. Dummy seeds and anatomical landmarks were identified on the scout
image and correlated to the CT. RESULTS: Verification CTs showed remarkable
consistency in the day-to-day drainage catheter position. The physician was able
to easily identify the small bowel of concern on the CT and determine if a safe
distance existed for treatment. CONCLUSIONS: The method outlined in this work
provides a safe means by which to treat bile duct obstructions using HDR when
critical structures are nearby. We were prepared to make real-time adjustments to
our treatment plan to account for significant variation, but found it unnecessary
to do so in this particular case.
PMID- 28517249
TI - SU-E-T-318: Source Position Localization for ICBT Tandem & Ovoid Applicators
Utilizing Oncentra Brachy Applicator Modeling.
AB - PURPOSE: Nucletron's Oncentra Brachy Applicator Modeling plugin (AMp) may
facilitate HDR cervical brachytherapy treatment planning when image artifact
inhibits dwell position localization. The AMp utilizes a 3D CAD rendering of the
corresponding applicator to define possible source dwell positions. This study
compares the equivalence of source localization within a CT/MR Fletcher-type
tandem and ovoid applicator utilizing clinical practice and Oncentra's AMp in a
water phantom containing OAR surrogate structures. METHODS: KVCT image sets were
acquired of a water phantom containing bladder and rectum surrogates as well as
an assembled Nucletron Fletcher CT/MR applicator with various ovoid sizes (20,
25, 30mm) and a 30 degrees tandem. Using Oncentra's Brachy TPS, OAR-surrogates
were segmented and catheters were reconstructed using (1) clinical protocols
(i.e. using source dwell position markers) and (2) using the AMp. Treatment plans
were generated following clinical protocol, ensuring 600cGy to the ICRU 38
defined Point A. The center coordinates of each active dwell position were
spatially compared. The dosimetric impact of these differences was quantified by
determining D0. 1cc, D1cc and D2cc for the surrogate OARs. RESULTS: Preliminary
results obtained for the 25mm ovoid / 30 degrees tandem applicator show 80% of
dwell positions defined by clinical protocol and the AMp agree within 1mm with a
maximum deviation of 1.17mm. Differences in source positions resulted in an
increase of 2.9%, 0.48% and 0.3% and 0.66%, 0.87%, and 0.59% for D0.1cc, D1cc and
D2cc for the bladder- and rectum-surrogates, respectively, when utilizing the AMp
rather than clinical protocol for source position localization. CONCLUSIONS:
Preliminary results indicate that source dwell position localization utilizing
Nucletron's Applicator Modeling plugin and our clinical protocol results in
equivalent dosimetry for the simple, water phantom geometry investigated.
Currently we are investigating the validity of this conclusion utilizing ovoids
of different sizes as well as a CT/MR-compatible vaginal cylinder.
PMID- 28517248
TI - SU-E-T-292: New Technique for Developing Proton Range Compensator Using Three
Dimensional Printer.
AB - PURPOSE: A new system for manufacturing proton range compensator (PRC) was
developed by using a three-dimensional printer (3DP). The physical accuracy and
dosimetrical characteristics of the new PRC (PRC-3DP) was compared with
conventional PRC (PRC-CMM) manufactured by computerized milling machine (CMM).
METHODS: A PRC for brain cancer treatment, with passive scattered proton beam,
was calculated in the TPS (Eclipse, Varian, USA) and its data was converted into
a new format for 3DP (Projet HD3000, 3D Systems, USA), using the in-house
developed software. PRC-3DP was printed with UV curable acrylic plastic, while
PRC- CMM was milled into PMMA using a CMM (V-CNC500, CINCINNATI, USA). We
measured the 5 randomly selected points for its physical thickness of both PRCs
to evaluate its physical accuracy. Stopping power ratio (SPR), spread-out bragg
peak (SOBP, 90~90%) and distal fall-off (DFO, 20~80%) at the central axis, +2.5,
and 2.5 cm in the lateral direction, and FWHM of dose profile in depth 6, 8, and
10 cm were measured to evaluate for its dosimetrical characteristics. All
measured data was compared with TPS data. RESULTS: There was no significant
difference in the physical depths between the calculated and the measured value
of both RPC-3DP and RPC-CMM (p<0.05). SPR of both PRC showed similarity in value
(1.022) when compared with that of the water. Average difference of SOBP between
the TPS and the measured data from both PRC was 0.3773+/-0.0075 and 0.2762+/
0.0235 cm, while DFO was 0.06+/-0.005 and 0.0471+/-0.0042 cm, respectively.
Average differences of FWHM between the TPS and the measured data from PRC-3DP
and PRC-CMM were 0.1799+/-0.025 and 0.137+/-0.0181 cm, respectively. There was no
significant difference in dosimetrical characteristic between the RTP and both
PRCs (p<0.05). CONCLUSIONS: Physical accuracy and dosimetrical characteristics of
the PRC-3DP were comparable to that of the conventional PRC-CMM, while
significant system minimization was provided. This work was supported by the
Technology Innovation Program, 10040362, Development of an integrated management
solution for radiation therapy funded by the Ministry of Knowledge Economy (MKE,
Korea). This idea was applied for a Korea patent (no. 10-2012-0010812).
PMID- 28517250
TI - SU-E-T-264: New Concrete Designed and Evaluation for Megavoltage X Radiotherapy
Facilities (CONTEK-RFH2).
AB - PURPOSE: The most common material for shielding is concrete, which can be made
using various materials of different densities as aggregates. New techniques in
radiotherapy, as IMRT and VMAT, require more monitor units and it is important to
develop specifically designed shielding materials. METHODS: Arraela S.L. has
developed new concrete (CONTEK(r)-RFH2), which is made from an arid with a high
percentage in iron (> 60%), and using the suitable sieve size, enables optimum
compaction of the material and a high mass density, about 4.1-4.2 g/cm3 .
Moreover, aluminate cement, used as base, gives high resistance to high
temperatures what makes this product be structurally resistant to temperatures up
to 1200 degrees C. The measurements were made in a LINAC Elekta SL18 to
energies 6MV and 15 MV with a field size of 10*10 cm2 for concrete samples in the
form of tile 25cm*25cm with variable thickness. RESULTS: The linear attenuation
coefficient, MUm, was determined for each energy by fitting the data to Eq. 1,
where Xxm is the exposure in air behind a thickness xm of the material, and X0 is
the exposure in the absence of shielding. These results are compared with the
ordinary concrete (2.35 g cm-3) for 6MV and 15MV energies (Ref. NCRP Report
No.151). Results are tabulated in Table1. Results of attenuation are compared
with ordinary concrete in Fig. 1. CONCLUSIONS: The new concrete CONTEK(r)-RFH2
increases photon attenuation and reduces the size of a shielded wall. A very high
percentage in iron and a suitablesieve size approximately double the density of
ordinary concrete. High mass attenuation coefficient makes this concrete an
extremely desirable material for use in radiation facilities as shielding
material for photon beam, and for upgrading facilities designed for less energy
or less workload.
PMID- 28517251
TI - SU-E-T-274: Monte Carlo Simulations of Output Factors for a Small Animal
Irradiator.
AB - PURPOSE: Measurement of dosimetric parameters of small photon beams, with field
sizes as small 1 mm in diameter, is particularly challenging. This work utilizes
Monte Carlo techniques to calculate percent depth dose (PDD) and output factors
for small photon fields from a kV x-ray based small animal irradiator. METHODS:
Absolute dose calibration of a commercial small animal stereotactic irradiator
(XRAD225, Precision X-ray) was performed in accordance with the recommendations
of AAPM TG-61 protocol. Both in-air and in-water calibrations were performed at a
30.4 cm source-to-surface distance (SSD) for a reference collimator 50 mm in
diameter. The BEAM/EGS was used to model 225 kV photon beams used for most
therapeutic applications. The Monte Carlo model was provided good agreement with
measured beam characteristics, e.g. PDD and off-axis ratios. Subsequently, output
factors for various square and circular applicators were measured using an
ionization chamber and radiochromic film, and compared with MC simulations.
Directional Bremsstrahlung splitting (DBS) was utilized for variance reduction to
improve efficiency of the output factor simulations. The statistical uncertainty
on the MC- calculated results is between 0.5% and 1% for most points. RESULTS:
The absolute dose measured for reference collimator at 30.4 cm SSD in water and
in air is 4.1 and 4.12 Gy/min. The agreement between simulated and measured
output factors was excellent, ranging from 1% to 2.84%. The MC- simulated and
measured depth dose data, normalized at the surface, show excellent agreement,
with a maximum deviation is approximately 2.5 %. CONCLUSIONS: Monte Carlo
simulation provides an indispensible tool for validating measurements of the
smallest field sizes used in preclinical small animal irradiation.
PMID- 28517252
TI - SU-E-T-298: Evaluation of the CNAO Spot Scanning Technique Based on the First
Clinical Deliveries.
AB - PURPOSE: The first Italian hospital-based facility for hadrontherapy is the
Centro Nazionale di Adroterapia Oncologica (CNAO) which started the clinical
activity on September 2011 with protons beams. The control of the treatment is
performed online by the Dose Delivery (DD) system which guides the whole
treatment by measuring beam characteristics as number of delivered particles and
beam position. The author will present the comparison between the required and
delivered quantities. METHODS: The CNAO facility is based on a synchrotron
designed to accelerate and deliver proton and carbon ion beams in the clinical
ranges. Unlike most of the proton-therapy centres, the delivery technique adopted
at CNAO is the "quasi-discrete" active scanning where dedicated magnets are used
to drive a pencil beam through the target and the beam is normally not switched
off during the transition between adjacent spots. These operations are performed
by the DD system which, based on the treatment planning and the online analysis
of dedicated beam monitor chambers, drives the scanning magnets. Spot by spot the
DD records data which allow the comparison between the measured number of
particles and position and the prescription. RESULTS: The data collected by the
dose delivery during the treatments were analyzed in detail, each treatment
consisting in more than 30 identical fractions. This allows checking the
stability and the accuracy of the CNAO delivery over identical spot sequences.
The comparison between the measured number of particles, the measured position of
each spot, and the corresponding prescribed quantities will be presented in
detail. Critical points will be discussed together with the proposed improvement
of the system. CONCLUSIONS: The results confirm the good performance of the CNAO
beam delivery obtained during the commissioning phase.
PMID- 28517253
TI - SU-E-T-285: Flatness as a Measure of Changes in Photon Energy for Megavoltage X-
Ray Radiotherapy.
AB - PURPOSE: To compare the sensitivity of flatness based energy metrics versus an
attenuation based metric (percent depth dose) as a function of energy changes
from the linac's nominal clinical energy. METHODS: Energy changes were
accomplished by adjusting the bending magnet current (BMI) +/-15% away from the
value used clinically. Two metrics for flatness, relative flatness in the central
80% of the field (flatness) and average maximum dose along the diagonals
normalized by central axis (CAX) dose (diagonal normalized flatness, DNF), were
measured using a commercially available ion chamber array (IC profiler, Sun
Nuclear, Melbourne FL). Percent depth dose was measured in water for depths of 5
and 10 cm in 3*3 and 10*10 cm2 field sizes. RESULTS: The sensitivity of percent
depth dose (PDD) and flatness to energy changes were smaller than changes in DNF.
For 6X the changes in PDD were from -1+ to +3% and the changes in flatness were
from -5% to +2% for energy changes of +/-15% from the nominal energy, for 18X the
PDD changed from -0.5% to +2.5% and the flatness from -5% to +2% over this energy
range. DNF changed from +12% to -8% for 6X and from +8% to -6% for 18X over a +/
15% change from the nominal energy and showed a near linear correlation with
energy. In addition DNF was the only metric that was found to be sensitive to
both increases and reductions of energy for both the 6 and 18 MV beams.
CONCLUSIONS: Diagonal normalizedflatness was found to be the most sensitive
metric to energy changes for photon beams of 6 and 18 MV. The IC profiler allows
this metric to be conveniently measured as part of routine linac quality
assurance. Sun Nuclear Corporation provided the IC profiler.
PMID- 28517254
TI - SU-E-T-307: Quantitative Assessment of the Source Attenuation for the New CT
Compatible Titanium Fletcher-Suit-Delclos (FSD) Gynecologic Applicator.
AB - PURPOSE: To quantify the effect of 192Ir source attenuation due to titanium
material used in manufacturing the new CT-compatible FSD device during treatment
delivery. METHODS: A typical cervical cancer treatment includes primary external
beam followed by a course of HDR Intra-Cavitary brachytherapy using FSD
applicator. A detailed geometry of the applicator obtained from the manufacturer
is implemented using Monte Carlo (MC) simulation package MCNP5. The bending
angles of tandem and colpostats are 150 and 1200 respectively. The source
geometry is of the VariSource wire model VS2000. We assigned 8 dwell positions in
the tandem and 4 dwell positions in each colpostat to calculate dose rate at
reference points with and without titanium wall present in the simulation.
RESULTS: Based on the MC computation, the titanium tube reduced the overall dose
to point A by ~1.5%, with contributions varying for each dwell position. We also
compare MC results with BrachyVision treatment planning system calculations. The
clinically used algorithm is based on AAPM report TG-43, which calculates the
dose without inhomogeneity correction. The latest Varian release of the planning
software BrachyVision-Acuros has the updated algorithm capable of inhomogeneity
corrected dose calculation. For this study a treatment plan is created based on
the exact coordinates of the MC model and used to calculate dose at reference
points. The dose to reference point A with BrachyVision traditional algorithm is
in excellent agreement with the homogeneous MC model result. CONCLUSION: The
attenuation due to Ti wall is ~1.5% at point A compared to ~5% using a non-CT
compatible system. Comparative accuracy of the two treatment planning systems
with MC, especially in their abilities to account for the source attenuation due
to the applicator titanium walls will also be presented.
PMID- 28517255
TI - SU-E-T-286: Verification of Treatment Delivery Monitor Unit (MU) Calculation and
Dose Estimation of Bilateral Total Body Irradiation (TBI).
AB - PURPOSE: TBI treatment delivery MU and patient dose estimation are calculated
manually at our institution. This study was to verify the accuracyof MU
calculation and dose estimation of bilateral TBI by application of tissue
heterogeneity correction. METHODS: Twelve TBI patients were simulated from neck
to thigh in bilateral TBI position. CT images were imported into the treatment
planning system (Philips, Pinnacle3). Treatment dose was prescribed to the
midpoint at the level of the umbilicus. Treatment distance was 519 cm. Both 6MV
and 23 MV opposite lateral beams delivered 200 cGy to the dose prescription point
with a 40 *40 cm2 field size and 45o collimator angle. A 1 cm thick spoiler was
placed about 15 cm from patient skin. Adaptive convolution superposition with and
without heterogeneity correction was used for calculation of MUs and doses at the
midpoints of the shoulder, chest, abdomen, and pelvis. RESULTS: Monitor units
calculated with heterogeneity correction were 1.1% and 0.9% smaller on average
than those without heterogeneity correction for 6MV and 23MV beams respectively.
The maximum deviations of MU were 3.8% and 2.8% smaller. Average percentage
differences of point doses with and without heterogeneity corrections were -0.2%,
17.0%, -0.3%, and -2.7% at the levels of shoulder, chest, abdomen, and pelvis for
6MV beam and 0.4%, 11.0%, 0.2%, and -1.7% for 23MV beam. Discrepancy of doses to
the points at the shoulder level varied from -6.8% to 8.9% for 6MV beam and from
1.6% to 5.1% for 23MV beam. CONCLUSIONS: Bilateral TBI MU calculation errors
caused by ignoring tissue inhomogeneity would be less than 4% and 3% for 6MV and
23 MV beam. Dose estimation is less accurate using 6MV beam and the inaccuracy
could be more than 8% for shoulder midpoint and 4% for pelvis midpoint.
PMID- 28517256
TI - SU-E-T-294: Maximizing the Availability of Positron Emitting Nuclei for Proton
Therapy Verification Using Different Beam Irradiation Sequences.
AB - PURPOSE: To demonstrate that the amount of nuclei available for post- irradiation
proton treatment verification using positron emission tomography (PET) can be
enhanced by reversing the beam delivery sequence in proton scanning beam
irradiations. METHODS: A time-dependent analytical model is used to calculate the
distributions of positron emitting nuclei for three different irradiation
sequences: a scattered beam and a scanning beam in both the conventional
sequence, distal edge first, and reverse sequence, distal edge last. The
simulated geometry emulates reference dosimetry measurements conducted at the
Paul Scherrer Institute (PSI). The reference measurements irradiate a 10 *10 cm2
field, delivering about 1 Gy to a 10 cm wide spread-out Bragg peak (SOBP).
Positron emitter availability with different beam sequence and imaging times and
the impact of the different irradiation sequences on the statistical error on a
range extrapolation were investigated. RESULTS: The ratio of the amount of
positron emitters from the distal last beam sequence to that from the distal
first sequence was 2.22 in the last centimeter of the SOBP. The comparison
between distal last and a scattered beam gave a ratio of about 1.7 in the same
region. In the distal last irradiation, more isotopes decay within a 120 second
window, than in a 240 second window using a distal first irradiation. The
statistical fluctuation on a range extrapolation was also smallest in the distal
last beam sequence. CONCLUSIONS: We demonstrated the effect of the irradiation
beam sequence on the isotope production relevant for the verification of proton
spot scanning therapy with PET. The largest amount of isotopes is available by
irradiating the distal edge last. This new beam sequence reduces the
PETmeasurement time while still offering higher counts and accuracy compared with
both the conventional beam sequence and the scattering method. This project was
supported by JSPS Core-to-Core Program.
PMID- 28517257
TI - SU-E-T-322: A Dosimetric Comparison of PBI Brachytherapy Techniques: SAVI,
Contura, and Tube and Button Applicators.
AB - PURPOSE: To evaluate the dosimetry of partial breast irradiation brachytherapy
techniques using the Strut Adjusted Volume Implant (SAVI), Contura, and Tube and
Button (T&B) applicators. METHODS: A total of 51 breast-cancer patients (23 SAVI,
6 Contura, and 22 T&B) were treated. The target was delineated following NSABP B
39 guidelines. 3D plans were optimized using the Inverse Planning Simulated
Annealing algorithm to deliver 3.4 Gy per fraction to the target and minimize
dose to organs at risk (OARs). Graphical optimization was then used to fine tune
the final dose distribution. The minimum cavity-to-skin distance was measured.
Target coverage (V90 and V95) and maximum dose (D0.1cc) to the OARs were
evaluated. Dose homogeneity index (DHI = 1-V150/V100) was calculated. RESULTS:
The average cavity-to-skin distances were 4.1 mm (0.5-9.6 mm, SAVI) and 11.7 mm
(7.1-15.4 mm, Contura). The target-to-skin distance for the T&B cases was 8.7 mm
(5.0-13.7 mm). The average V90 and V95 to the target were 96.8% and 94.5% (SAVI),
97.0% and 93.0% (Contura), 98.6% and 97.3% (T&B). The mean D0.1cc to the skin,
ribs, and lung was 91.5%, 58.8%, 44.5% (SAVI), 93.1%, 51.3%, 40.5% (Contura),
69.1%, 41.5%, and 31.9% (T&B). The average V150 and V200 to the normal breast
tissue were 30.4 cc and 14.9 cc (SAVI), 29.5 cc and 7.3 cc (Contura), 18.3 cc and
7.1 cc (T&B). The average DHI for the SAVI, Contura, and T&B cases was 0.55 (0.50
0.60), 0.70 (0.63-0.78), and 0.76 (0.74-0.79). CONCLUSIONS: All techniques
provided clinically acceptable target coverage and dose to the OARs. The SAVI
device provided a lower skin dose at close cavity-to-skin distances while
providing excellent target coverage. However, the T&B and Contura applicators
produced more homogeneous dose distribution (higher DHI) in the target than the
SAVI. The correlations between dosimetric properties and follow-up mammogram
results are under investigation.
PMID- 28517258
TI - SU-E-T-268: Evaluation of Photoneutron Contamination in Elekta Synergy-S High
Energy Linear Accelerator and Indigenous Novel Solution: The AIIMS Experience.
AB - PURPOSE: The photoneutron contamination problem was encountered due to laminated
barrier wall and short maze. The purpose of this study was to report our
experience in evaluating the photoneutron contamination during radiation safety
survey and solution. METHODS: The photoneutron contamination measurement was
carried out in Elekta Synergy-S high-energylinear accelerator for 15MV beam. A NE
Neutron survey meter and for photon, Victoreen and RADOS survey meters were used.
The laminated barrier wall composed of 37cm steel with 30cm concrete both side
and short maze length of 5 meter. During safety survey, higher photoneutron
levels for 15MV X-rays at treatment room door found. The effect of photoneutron
contamination as function of neutron shielding materials of wood, polyethylene
and boron and thickness, distance, locations and directions to the control
console at distance upto 7 meter were investigated for 4 gantry angles at
locations of treatment room entry doors namely door1(A), door2(B), console(C),
conduit (D) and above-ceiling(G) for 15MV. RESULTS: The initial safety survey
showed that neutron level of 47mR/h and photon leakage of 3.2mR/hr at the
treatment entry room door1. The neutron values could bring down to the level of
acceptance at the treatment entry door2, but the photon values are not
acceptable. Therefore, 30cm concrete wall block was made at the location of door2
and another bend was taken. Finally, treatment entrance room door was made using
3cm polyethylene neutron shielding materials in order to achieve the both neutron
contamination and photon leakage within the acceptable levels. CONCLUSIONS: The
neutron sliding-door is operated manually in finger-push by technologist for day
to-day usage. This simple solution is cost effective and increases the patient
throughput. This study underlines that one needs to take appropriate safety
measures prior to facility design whenever the space constraints situations
arises for high energy linear accelerator.
PMID- 28517259
TI - SU-E-T-278: Study of MAGIC-F Gel and PENELOPE Code Simulation Response for
Clinical Electron Beams.
AB - PURPOSE: To evaluate the response of MAGIC-f gel through dose response curves,
percentage depth dose (PDD) and beam profile for clinical electron beams.
METHODS: Glass tubes (Vacutainer (r)), with 6 cm length and 0.5 cm radius, with
MAGIC-f were positioned inside a water phantom to study the gel response with
doses from 0.5 Gy to 20 Gy in electron beams of 6, 9 e 12 MeV. Glass tubes of 20
cm length and 1 cm radius and PMMA phantoms of 10 * 5 * 5 cm3 were used to PDD
and beam profiles determinations, respectively, with a maximum dose of 2 Gy to
the gel. The samples were analyzed through magnetic resonance imaging (MRI) with
a 3 T tomography using a head coil, multiple spin echo sequence with 16 echos, TE
15ms and TR 4000ms. The MAGIC-f response was simulated with PENELOPE Monte Carlo
code in the same geometry used in the irradiations. The results obtained with
MAGIC-f and PENELOPE were compared with clinical data. RESULTS: Calibration
curves for MAGIC-f showed a linear behavior, with correlation coefficient of
0.99, for all energies. The PDD and beam profile curves obtained with MAGIC-f
presented differences lower than 1.5% and 3.0%, respectively, when compared to
clinical data. Results obtained by PENELOPE and clinical data showed differences
up to 1.0% and 1.5%, respectively, for PDD and profile curves. CONCLUSIONS: The
dosimetric parameters for electron beams obtained experimentally with MAGIC-f and
with PENELOPE code showed similar results to the clinical data. From the results
it can be inferred that MAGIC-f can be used as a complementary dosimetric tool
for electron beams due to its characteristics of high spatial resolution and the
ability to construct tridimensional dose distributions. Also PENELOPE can be used
to study MAGIC-f gel response in electron beams.
PMID- 28517260
TI - SU-E-T-300: Monte Carlo Simulation of Single-Plane Magnetically Focused Narrow
Proton Beams.
AB - : Purpose To investigate narrow, elongated magnetically focused proton beams and
compare their properties with passively collimated beams using Monte Carlo
simulation. METHODS: We performed Geant4 Monte Carlo simulations involving a
single quadrapole focusing magnet, thereby creating a flattened beam with an
elongated elliptical cross section. The parameters of the magnet were chosen to
mimic k=3 (quadrapole) Halbach cylinders that are available commercially as
assemblies of rare earth permanent magnetic materials. For comparison,
simulations were also performed with the same beam line components and passively
collimated beams (using an elliptically shaped collimator). To facilitate fair
comparison, efforts were made to closely match the planned treatment volumes
(PTV) for each simulation case in dose, volume, and major and minor diameters of
the elliptically shaped PTV at Bragg depth. RESULTS: Magnetic focusing delivered
significantly better dose localization to the target over collimated beams which
are the current beam delivery modality. Compared to collimated beams, the
magnetically focused beams showed a 31% smaller therapeutic ratio, a 31% smaller
integrated dose, a 34% smaller entrance dose, a 30% larger peak-to-entrance
central depth dose ratio, a 37% smaller penumbra volume, and were 35% more
efficient in dose delivery (based on proton number). CONCLUSIONS: The clinically
relevant advantages of the magnetically focused beams compared to the collimated
beams (the current standard of care) can be attributed to the preferential
directional acceleration of protons due to the magnetic field. Our simulations
suggest such magnets can be used to deliver tissue sparing doses to normal and at
risk tissue, and enhanced dose to elongated, narrow targets. Future work to
characterize and test prototype magnets is in progress. Such beams my find
application in novel proton treatments including application to the spinal cord.
PMID- 28517261
TI - SU-E-T-289: On the Use of a Diode Array for the Commissioning of Dynamically
Wedged Asymmetric Fields Generated by Varian EDW's in the Pinnacle Treatment
Planning System.
AB - PURPOSE: To present a validation study of enhanced dynamic wedges (EDWs)
implemented into Pinnacle3 treatment planning system (TPS) using a diode array,
Monte Carlo (MC) simulation, and measurements. METHOD AND MATERIALS: Modeling of
EDW dose distribution in the Pinnacle3 TPS is based on a combination of open
field beam data and the Varian 'Golden Segmented Treatment Table' (GSTT) unique
to each photon beam. To validate the EDW models, dose profiles of 6- and 10-MV
photon beams from a Clinac 2100C/D were measured in virtual water at depths from
near- surface to 30 cm for a wide range of asymmetric field sizes and wedge
angles using the Profiler-2 diode array system. The EDW output factors for
asymmetric fields were measured in solid water using a small-volume cylindrical
ionization chamber placed at a depth of 10 cm on the central axis. In addition,
absolute doses on central axis at depths of 5, 10, 15 and 20 cm were measured in
virtual water using a small-volume cylindrical chamber for comparison with the
collapsed-cone convolution (CCC) calculations. The 6- and 10-MV photon beams
emerging from the treatment head of the Clinac 2100C/D were fully simulated using
the Monte Carlo code BEAMnrc and DOSXYZnrc. This code was used to calculate the
central-axis percentage depth doses and dose profiles for the open and
dynamically-wedged fields in a water phantom. RESULTS: The off-axis dose profiles
of various EDWs computed with the CCC dose model and MC simulations agreed with
measured EDW dose distributions to an accuracy of better than 2%/2 mm. Measured
EDW output factors used for MU calculations in Pinnacle3 TPS agreed with MC
predictions within 1-2%. CONCLUSIONS: The utility of Profiler-2 diode array
system to measure dose profiles for commissioning of EDWs into the Pinnacle3 TPS
has been demonstrated to have acceptable accuracy for clinical implementation.
PMID- 28517262
TI - SU-E-T-311: Dose Perturbation Due to Thin Layers of High-Z in HDR Ir-192 Source
Dose Delivery.
AB - PURPOSE: To evaluate the dose perturbation associated with thin layers of high-Z
materials in HDR 192I source dose delivery through Monte Carlo simulation and
experimental measurement. METHODS: Dose perturbation of high-Z thin materials in
HDR 192Ir source dose delivery was experimentally and theoretically studied.
MCNP5 Monte Carlo simulation code was employed to calculate the dose enhancement
effects at upstream and downstream of high-Z materials. The cutoff energy for
photon was 1 keV and for electron 5 keV. A parallel plate ion chamber with window
thickness of 0.9 mm, was used to measure the dose rates at the downstream of the
high-Z thin layer. The high-Z layer was positioned at 0.625 cm from the 192Ir
source. The thickness of layer was from 0.1 to 1 mm. The results were normalized
by the dose rate in a homogeneous water phantom at the location of the interface.
The high-Z materials used were lead, tin and titanium. In addition, the dose
enhancement effects of different high-Z materials at the shortest distance from
the interface were also calculated and measured to examine the Z dependence.
RESULTS: The Monte Carlo simulation results agreed very well with the
experimental data. At the surface of the 0.1 mm high-Z interface, Ti, Sn and Pb
respectively increase dose rate by 1.2, 1.4 and 2.5 times the dose rate in
homogeneous water medium. The dose rate enhancement depends on Z and thickness of
the high-Z layer. The dose enhancement increases with Z. However, an increased
thickness in the high- Z layer results in less dose enhancement due to
attenuation. CONCLUSIONS: HDR 192Ir source dose enhancement by a high-Z material
thin layer is similar to that reported from a kilo-voltage X-ray beam. Attention
should be paid for high-Z thin layers with HDR source clinically as it could
cause significant dose enhancement.
PMID- 28517263
TI - SU-E-T-272: Commissioning an Orthovoltage Unit Used for Radiobiology Research.
AB - PURPOSE: Orthovoltage X-ray units are used to irradiate cell cultures or small
animals in research. Beam characteristics of these units are often not well
understood and only nominal dose specified is used by researchers in their
studies. This work describes commissioning of an orthovoltage unit similar to
that of a linear accelerator. METHODS: The X-Rad 320 Orthovoltage unit is a self
contained x-ray system which can be operatedwithin a wide range of kVp and mAs
settings. This work characterizes the beam produced by this system. Various beam
data, including depth dose, cross profiles, collimator and total scatter factors,
have been measured. Collimator and total scatter measurements were done with
cylindrical farmer chambers (0.6 cc and 0.057 cc volumes) for field sizes ranging
from 2*2 to 20*20 cm2 . Sc measurements were done in air at 50 cm SCD and Sc,p
measurements were done in 2 cm depth of phantom at 50 cm SSD.The depth dose
curves were generated for three different field sizes for depths up to 15 cm. A
parallel plate chamber was used for surface and near surface dose measurements
while the cylindrical chamber was used for other depths. RESULTS: Measurements of
Sc and Sc,p indicate minimal variation of these factors with field size, except
for very small fields. The results of depth dose measurements produce results
comparable with published data for similar beams and indicate a very small dose
buildup at shallow depths. CONCLUSIONS: Proper characterization of an x-ray beam
and accurate dosimetry is of importance in radiobiology investigations which may
lead to advent of new therapies for humans. This work investigates the beam
characteristics of an orthovoltage unit to ensure accurate irradiation of
samples. The data collected here could further be used for simulation of dose
distribution within irradiated volume.
PMID- 28517264
TI - SU-E-T-314: Evaluation of Dosimetric Impact of Catheter-Position Uncertainty in
Balloon High Dose Rate Brachytherapy of Breast Cancer.
AB - PURPOSE: To evaluate the dosimetric impact of catheter-position uncertainty prior
to each fraction in balloon high dose rate (HDR) brachytherapy for breast cancer.
METHODS: For 30 balloon HDR patients, each dwell position of the catheters was
manually shifted distally (+) and proximally (-) with a magnitude of +/-1 mm, +/
2 mm, +/-3 mm and +/-4 mm. A total of 240 plans were retrospectively produced and
compared to clinical treatment plans to simulate catheter-position uncertainty.
The following dosimetric data were evaluated: PTV_EVAL V90[%] after subtracting
air/seroma volume, skin and rib maximal dose (Dmax[%]) and normal breast tissue
V200[cc]. RESULTS: PTV_EVAL V90 was decreased in 93% of cases while increased
with maximum value of < 0.7% in 7% of cases. Average/maximal reduction was
increased from 0.3%/1.2% (+/-1 mm), 1.0%/3.5% (+/-2 mm) and 2.6%/6.2% (+/-3 mm)
to 5.0%/9.2% (+/- 4 mm) as catheter-position error was increased. Change of skin
and rib Dmax values was case-specific. They were increased in 52% of cases while
decreased in 48% of cases. As catheter-position error was increased, the
average/maximal deviation was increased from 1.6%/9.3% (+/-1 mm), 3.1%/19.1% (+/
2 mm) and 4.6%/29.1% (+/-3 mm) to 6.3%/40.2% (+/- 4 mm). Normal breast tissue
V200 was increased in 90% of cases while decreased with maximum value of < 0.4cc
in 10% of cases. Average/maximal increase was elevated from 0.3cc/1.2cc (+/-1
mm), 0.8cc/2.9cc (+/-2 mm) and 1.8cc/4.8cc (+/-3 mm) to 2.9cc/6.7cc (+/- 4 mm) as
catheter-position error was increased. CONCLUSIONS: The catheterposition
tolerance of +/-2 mm set by the AAPM TG 56 is clinically acceptable for most
clinical cases. However, in a case where the dosimetric data of treatment plan
are close to the dosimetry limits of the clinical protocol, smaller tolerances
such as +/-1 mm or zero tolerance is clinically recommended to minimize delivered
dose discrepancy from the planned dose.
PMID- 28517266
TI - SU-E-T-273: Commissioning Motorized Jaws for a Micro-CT/RT.
AB - PURPOSE: To design, construct and commission a set of computer-controlled
motorized jaws for a micro-CT to perform conformal image-guided small animal
radiotherapy. METHODS: We report on the design and evaluation of our custom-built
motorized orthogonal jaws, which allows the delivery of off-axis rectangular
fields, installed on a GE eXplore CT 120 preclinical imaging system. The jaws in
the x direction are independently driven, while the y direction jaws are
symmetric. All motors have backup encoders, verifying their positions.
Measurements were performed using the large focal spot (1.0 mm) at 140 kVp, 50
mA, 25 ms pulse duration, with 220 ms between pulses. Additionally, a Monte Carlo
beam model of the micro-CT and jaws has been created in BEAMnrc. Square beam
profiles (2 * 2, 5 * 5, 10 * 10, 20 * 20 and 30 * 30 mm) were measured using EBT2
film in the center of a 40 * 40 * 40 mm solid water block. A calibrated Farmer
ion chamber in a 50 * 20 * 70 mm solid water block was used to measure the output
of three field sizes: 50 * 50, 40 * 40 and 30 * 30 mm. Both setups were simulated
in DOSXYZnrc. Films were scanned on a flatbed scanner (Epson 1000XL) and
converted to dose using a fitted calibration curve. RESULTS: Relative output
factors measured with the ion chamber agree with Monte Carlo simulations within
2%. Penumbra widths from film agree well with simulations. The averaged random
error of positioning both jaws is estimated at less than 0.1 mm. Finer
calibration points will improve the absolute jaw positioning errors. CONCLUSION:
The computer-controlled motorized jaws can be positioned reliably down to sub
millimeter resolutions. Upon completion of small field dosimetry (< 1 cm), this
will be ready for conformal radiotherapy for small animals.
PMID- 28517265
TI - SU-E-T-317: Dynamic Modulated Brachytherapy (DMBT): Robotic Applicator Design.
AB - PURPOSE: To investigate the hardware necessary for implementing our Dynamic
Modulated Brachytherapy (DMBT) treatment concept for rectal cancer. METHODS: The
DMBT robot has three major parts: 1) shield and shield delivery module, 2)
controlling module, and 3) DMBT controlling and monitoring software. The shield
is a tungsten alloy cylinder (r=0.95cm, l=4.5cm) with a 5.5mm rectangular-shaped
opening. The shield is controlled by an aluminum pipe with gear set (1:3) and
linear actuator (2mm/turn). An Ir-192 radiation source will be placed through the
aluminum pipe. The power source is a Nema-17 stepping motor with EvoDrive ST-17
(EVA Robotics, Queensland, Australia) and USB-6009 DAQ (National Instrument,
Austin, TX). With our in-house operating program through LabView (National
Instrument, Austin, TX), we can make and load plans for treatment as well as
testing. Checking the shield position is also possible through the operating
program. For safety, a lexan sheath tube and emergency buttons are built-in.
RESULTS: The DMBT robot has 2 degrees of freedom, which are linear translation
and rotation. With our power delivery system, the spatial resolutions are
0.0125mm (linear stage) and 0.012Es (rotation). In 0.5s, motors achieve the
desired position with the maximum speeds 450 step/s (1Es), 7,500 step/s (30Es),
and 12,000 step/s (5mm). Four registers are triggered with USB-6009 DAQ signals.
The operating program includes gages for checking shield position, loading
treatment plans, and safety buttons. CONCLUSIONS: In all, we have designed the
hardware components of the DMBT system for rectal cancer. For treatment, the
system needs more elements to support the DMBT robot; lexan sheath tube holder,
DMBT robot security joint, and a system for reducing friction between the tube
and shield. We will also refine our system to be more compact by using DC
servomotors instead of the larger Nema-17 stepping motors.
PMID- 28517267
TI - SU-E-T-284: Surface Dose Evaluation for Beams with and without Flattening Filter
in Breast Cancer Treatment.
AB - PURPOSE: To evaluate surface doses for beams with and without flattening filter
(FF and FFF) in breast cancer treatment plans. Measurements were performed for
validation. Delivery:TrueBeam, used in this study, is a linear accelerator newly
designed to deliver both flattened and flattening filter free beams. Planning:
Eclipse treatment planning system (TPS) is commissioned and utilized. We used 6
MV half beams from FFF mode to plan standard tangential breast treatments due to
its similar shape to wedged FF beams. We compare these plans with those from 6MV
flattened beams with 30 degrees wedges. Measurement Validation: We used a Rando
phantom and InLightTM nanoDots Optically stimulated luminescence dosimetry(OSLD)
system to measure surface doses from FFF beams. Medial, apex and lateral
locations from central plane, as well as positions from caudal and cranial
regions, were included. RESULTS: Planning comparison: surface doses from plans
with FFF beams were2.2%-4.7% lower than those with flattened beams with wedges,
when doses at deeper depth from central axis stay close in value. Measurement
validation: In the apex region of central plane,the OSLD readouts are 4.5% - 6.3%
higher than calculated. In the caudal, cranial and medial regions, TPS
underestimated the surface dose from 7.2-8.7%. CONCLUSIONS: For standard
tangential breast plans, surface doses are lower with FFF beam than with
flattened beams with wedges. The surface doses from FFF beams were validated with
OSLD measurements, taking into account the uncertainty of the dosimeter and its
angular dependence.
PMID- 28517268
TI - SU-E-T-306: An Optimized Dosimetry Study Comparing a Multichannel Cylinder versus
Single Channel Cylinder in the Treatment of the Vaginal Cuff or Vagina with High
Dose Rate Brachytherapy.
AB - PURPOSE: Elekta/Nucletron introduced a new CT/MRI multi-lumen brachytherapy
applicator to optimize dosimetry and treatment of vaginal targets. The design
includes several peripheral channels isotropically placed 5mm inside cylinder
surface with a separate central channel allowing single lumen brachytherapy as an
option. We compared optimized dosimetry plans between single channel versus multi
channel to determine potential dosimetric advantages in vaginal cancer treatment
after hysterectomy. METHODS: Patients were planned by CT simulation with each
fraction of vaginal brachytherapy for postoperative endometrial cancer or vaginal
cancer. Twenty CT cases representing five patients were compared. A single
channel (standard) treatment approach was planned to the prescribed depth with
the goal of providing maximal coverage to the tumor bed (the 5mm rind typically).
Doses to the bladder and rectum were recorded by dose volume histogram. A second
treatment plan was generated using a multichannel approach. The Oncentra
brachytherapy planning system was used to generate both forward and IPSA inverse
treatment plans. The target coverage percentage and doses to the bladder and
rectum were optimized. RESULTS: The comparison demonstrates an improved V90, V95,
V100 of the prescribed dose to the 5mm vaginal cuff rind was achieved in all
cases. The average improvement in coverage was 9% (between 6-13%) for the cases
evaluated. The multi-channel plan also reduced the maximal dose (hot spot) to the
bladder and rectum within a range of 9-16% and 5-15% respectively. An increased
non-critical vaginal mucosal dose of up to 75% was delivered as a result of the
reduced bladder and rectal exposure via multichannel procedure. CONCLUSIONS:
Optimization of vaginal cuff brachytherapy is possible by using a new multi-lumen
vaginal cylinder. The new device can increase the therapeutic ratio by improving
target coverage with a reduction in the potential toxicity of hot spots to the
adjacent organs.
PMID- 28517269
TI - SU-E-T-321: Dynamic Modulated Brachytherapy.
AB - PURPOSE: We introduced the concept of Dynamic Modulated Brachytherapy (DMBT) for
rectal cancer, last year. To continue our work, we studied different shield
designs and investigated the system's tolerance against systematic setup errors.
METHODS: As previously presented, our system uses a cylindrical tungsten shield
to create a directional radiation profile, which is modulated through translation
and rotation using a specialized robotic arm. We used Monte Carlo simulations and
an in-house gradient projection optimization algorithm to look at key design
parameters. First, we used ideal phantoms to study treatment quality from shield
radii ranging 0.5-1.5 cm in 0.25 cm increments. Second, using 36 patient plans,
the dependence on radial source position within the shield was studied. We also
analyzed the tolerance of the system to systematic setup errors by simulating
dose distributions from possible inaccuracies. These included translational and
rotational errors as well as possible Ir-192 source misplacements by the
afterloading system. RESULTS: Changes in shield radius followed steady patterns.
Increasing the radius showed a consistent increase in dose conformality to the
tumor volume and better sparing to surrounding tissues. However, there was also a
linear increase in total dwell time. There was a trade off to changing the radial
position of the source. As the source is brought away from the center, there is a
decrease in conformality to the tumor volume, but sparing to healthy tissues was
increased and there is a decrease in total dwell time. We found that any
potential setup errors for our system, within anticipated margins, had negligible
effects on the dose distributions (< 3% deviation). CONCLUSION: Various
parameters for shield designs must be balanced for an effective DMBT application.
It was found that the system is highly robust against systematic setup
uncertainties.
PMID- 28517271
TI - SU-E-T-277: Hypothesis and Design of an Integrated X-Ray/Bioluminescent Imaging
(BLI) and Tomography (BLT) System for the Study of Radiation and Treatment in
Small Animals.
AB - PURPOSE: Design and construct an integrated x-ray/bioluminescent tomography (BLT)
system (with BLT being our initial focus) that can function as a standalone
research apparatus and also on-board the SARRP to guide focal irradiation. In
addition, it is aimed to enhance the BLT of the system to improve target
localization by incorporating multi-projection, multi-spectral BL images, as well
as CT 'priors'. METHODS: The SARRP system integrates a portable robotic
translational/rotational stages system and an x-ray source which in the new
system development the x-ray source is replaced with the PXS10-65 W model rated
at maximum 130 kV having a variable small focal. A high performance, low noise,
CCD camera mounted on a light-tight housing along is used for the aim of the BL
imaging and tomography. In the new setup of the BLI system, the camera-filter
mirror assembly is attached to a motorized gantry to acquire images in angles
between to while the position of the camera does not block the path of the x- ray
beam. Innovatively, a 3-mirror arrangement is implemented to eliminate the need
to rotate the CCD camera for capturing images. Furthermore, the robotic stage can
be vertically adjusted to allow BLI imaging of multiple animals. RESULTS: To
validate the accuracy with the on-board x-ray and BL tomography can be used to
localize a BL tumor target and the minimum beam expansion to ensure radiation
coverage of the target. The validation will employ phantoms and
immunohistochemistry analysis of radiation damage in irradiated BL tumor models
in vivo. The proposed system is currently under development and envisioned to be
calibrated and evaluated along with the stand-alone radiation system.
CONCLUSIONS: The novelty of embedded BLI guidance system is to enable the
unprecedented focal irradiation of the small volumes of tumors which are more
realistic in human disease.
PMID- 28517270
TI - SU-E-T-267: Construction and Evaluation of a Neutron Wall to Shield a 15 MV Linac
in a Low-Energy Vault.
AB - PURPOSE: To design and quantify the shielding efficacy of an inner Borated
Polyethylene (BPE)wall for a 15 MV linac in a low energy vault. METHODS: A Varian
TrueBeam linac with a maximum photon energy of 15 MV was installed in asmaller,
preexisting vault. This vault originally housed a low-energy machine and did not
havesufficient maze length recommended for neutron attenuation. Effective dose
rate calculationswere performed using the Modified Kersey's Method as detailed in
NCRP Report No. 151 andfound to be unacceptably high. An initial survey following
the machine installation confirmedthese calculations. Rather than restrict the
linac beam energy to 10 MV, BPE was investigatedas a neutron moderating addition.
An inner wall and door were planned and constructed using4'*8'*1" thick 5% BPE
sheets. The resulting door and wall had 2" of BPE; conduits and ductwork were
also redesigned and shielded. A survey was conducted following construction of
thewall. RESULTS: The vault modification reduced the expected effective dose at
the vault door from 36.23to 0.010 mSv/week. CONCLUSION: As specific guidelines
for vault modification are lacking, this project quantitativelydemonstrates the
potential use of BPE for vault modification. Such modifications may provide alow
cost shielding solution to allow for the use of high energy modes in smaller
treatment vaults.
PMID- 28517272
TI - SU-E-T-299: Proton Pencil Beam Spot Scanning Phase Space in the IBA System and
the Clinical Implications for Superficial Targets.
AB - PURPOSE: In the treatment of superficial lesions with proton Pencil Beam Scanning
(PBS), spot size is dominated by the nozzle contribution. Accuracy of phase-space
modeling is therefore paramount. IBA's Dedicated (DN) and Universal Nozzles (UN)
have different designs and, consequently, characteristics. Here we report the
phase spaces of these two nozzles, without and with a range shifter (RS).
METHODS: In-air spot fluence measurements were made for five proton energies:
225, 210, 180, 150 and 115 MeV and at five distances from isocenter pertinent to
SAD-type treatments: +33, +20, +10, 0 and -10 cm ('+' implies upstream), without
and with a 7.5 cm water-equivalently-thick RS (sufficient to pull back the lowest
energy Bragg peak to patient surface), fixed with its upstream side 41 cm from
isocenter. Data collected on a fixed horizontal beam-line with a DN and a gantry
mounted UN were compared. The full-width-at-half-maximum (FWHM) of a Gaussian fit
to each spot fluence profile was extracted along the two principal axes. RESULTS:
With no RS, the proton spots are ~20-70% larger at isocenter in the UN than in
the DN. Spots are less asymmetric, and eccentricity increases more slowly with
energy, in the UN than in the DN. Over the 33 cm in-air travel upstream of
isocenter, the spot FWHM varies by less than ~2 mm. However, spot asymmetry
becomes more severe upstream (for 115 MeV spots, 30-40% compared to <20% at
isocenter for DN, but similar and <10% for UN). With an RS, spot FWHM at
isocenter increases by 12.7 mm from 8.3 mm (DN) and 10.7 mm from 13 mm (UN) for
150 MeV protons (typical for brain treatments). With no RS, relatively distance
independent spot size facilitates SAD-type treatments. For patients with
superficial lesions, where an RS is required and the phase space varies rapidly
with distance, the RS should be permitted at two additional locations. US Army
Medical Research and Materiel Command under Contact Agreement No. DAMD17-W81XWH
04-2-0022.
PMID- 28517273
TI - SU-E-T-288: Skin Dose Measurement of Whole Brain with GAFCHROMIC EBT2 Films.
AB - PURPOSE: To measure skin dose of whole brain irradiation of a humanoid unsliced
phantom treated by standard lateral fields with GAFCHROMIC EBT2 films. METHODS:
The head and neck of the whole body phantom was scanned at the slice thickness of
2mm. A whole brain plan using 6MV beam was created with standard parallel opposed
lateral fields. The isocenter was placed at the outer canthus to avoid divergence
to orbital structures. The plan was normalized to the calculation point and with
= 95% of brain volume covered by = 95% of prescription dose. The EBT2 films were
carefully cut and labeled with same orientation in the film calibration and skin
dose measurement. EBT2 film was calibrated in the reference condition with
various dose (0-10Gy). After the phantom was positioned for treatment and correct
setup was verified by kV-kV imaging and CBCT, the films were placed at various
sites and irradiated. An Epson flatbed color scanner was utilized and the scanner
response from the red channel of the RGB image was used as the density value for
the estimation of dose. The comparison was made between the measured dose and the
planned dose for different head locations. RESULTS: Our preliminary results
indicated that the measured skin dose agrees with the planned dose within 10% for
the sites centered in the treatment fields such as mid right/left sphenoid bones.
For the sites outside or near the edge of the treatment fields, such as the
right/left orbits and low chin, the measured dose is significantly different from
the planned dose (>15%). CONCLUSIONS: Skin dose of whole brain irradiation could
be measured by GAFCHROMIC EBT2 films. The difference between the measured dose
and the planned dose varies significantly depending on the location of interest
relative to the treatment field. Further investigation is needed.
PMID- 28517274
TI - SU-E-T-310: Micro-Dosimetry Study of the Radiation Dose Enhancement at the Gold
Tissue Interface for Nanoparticle-Aided Radiation Therapy.
AB - PURPOSE: Gold nanoparticles (AuNP) have been proposed to be utilized for local
dose enhancement in radiation therapy. Due to a very sharp spatial fall-off of
the effect, the dosimetry associated with such an approach is difficult to
implement in a direct measurement. This study is aimed at establishing a micro
dosimetry technique for experimental verification of dose enhancement in the
vicinity of gold-tissue interface. METHODS: The spatial distribution of the dose
enhancement near the gold-tissue interface is modeled with Monte Carlo (MC)
package MCNP5 in a 1-dimentional approach of a thin gold slab placed in an ICRU-4
component tissue phantom. The model is replicating the experiment, where the dose
enhancement due to gold foils having thicknesses of 1, 10, and 100MUm and areas
of 12.5*25mm2 are placed at a short distance from clinical HDR brachytherapy (Ir
192) source. The measurements are carried out with a thin-film CdTe-based
photodetector, having thickness <10MUm, allowing for high spatial resolution at
progressively increasing distances from the foil. RESULTS: Our MC simulation
results indicate that for Ir-192 energy spectrum the dose enhancement region
extends over ~1 mm distance from the foil, changing from several hundred at the
interface to just a few percent. The trend in the measured dose enhancement
closely follows the results obtained from MC simulations. CONCLUSIONS: AuNP's
have been established as promising candidates for dose enhancement in
nanoparticle-aided radiation therapy, particularly, in the energy range relevant
to brachytherapy applications. Most researchers study the dose enhancement with
MC simulations, or experimental approaches involving biological systems, where
achievable dose enhancements are difficult to quantify. Successful development of
micro-dosimetry approaches will pave a way for direct assessment of the dose in
experiments on biological models, shedding some light on apparent discrepancy
between physical dose enhancement and biological effect established in studies of
AuNP-aided radiation therapy. No conflict of interest.
PMID- 28517275
TI - SU-E-T-271: Irradiating a Single Hippocampus in a Small Rodent Using VMAT-
RapidArc SRS: Preliminary Data.
AB - PURPOSE: To develop and optimize the procedures for the precise irradiation of
the hippocampal region in a rodent with minimum radiation dose to the remainder
of the brain. For this purpose, VMAT-RapidArc SRS was used to irradiate one
hippocampus of athymic nude (ATN) rats. Prescribed dose was verified through TLD
measurements and spared brain region(s) were confirmed through
immunohistochemical analysis postmortem. METHODS: Seven ATN rats, 10-12 weeks old
underwent human-like radiation treatment planning followed by SRS. MRI and CT
axial images of 0.8 mm thickness of the rat's skull were acquired and transferred
to ECLIPSE treatment planning software where brain, right and left hippocampi
were contoured. A VMAT-RapidArc plan consisting of two 3600 axial arcs and two
1200 vertex arcs irradiated the left hippocampus only to a dose of 10 Gy.
Treatment was delivered using a 6 MV photon beam from a Trilogy Linac equipped
with OBI. TLD measurements were performed prior to treatment using a custom made
phantom that simulated the rat's brain and body. Orthogonal x-ray images taken
with the OBI and co-registered to DRR images were used to adjust the rat's
treatment position. One month post- irradiation, rats were sacrificed and brain
dissection was performed to verify the radiation effects in the targeted and non
targeted regions. RESULTS: Percent differences between calculated and measured
dose were ~12% which was expected due to the small field sizes (<2cm) used.
Immunohistochemistry analysis revealed a significant reduction in cell population
in the ipsilateral hippocampus while cell populations comparable to those in a
non-irradiated subject were observed in the contralateral hippocampal region.
CONCLUSIONS: Present results demonstrate that precise irradiation of small
volumes within a rat's brain can be achieved with human-like image-guided VMAT
RapidArc treatment. Postmortem analysis of the rat brain provides evidence of
high-precision targeted radiation damage and dose sparing.
PMID- 28517276
TI - SU-E-T-297: Proton-Therapy System for Treatment of Macular Degeneration and
Ocular Malignancies.
AB - PURPOSE: To commission a proton-therapy system for the treatment of uveal
melanoma and age-related macular degeneration. METHODS: Proton therapy system is
the proto-type of a commercial product developed by Ion Beam Applications. Proton
beam is brought into the treatment room at 105 MeV through a fixed beam line. A
single-scattering system with absorber/scattering foils spreads the beam into a
Gaussian profile. A library of 10 range-modulator wheels and 16 range-modulator
blocks generate spread-out Bragg peaks of various range and modulation width.
Source-to-axis distance of the system is 169 cm. Two orthogonal digital x-ray
panels are used for alignment. EyePlan software is used both for both treatment
planning and in-room alignment. RESULTS: Range can be varied continuously between
0.5 and 3.4 g/cm2 . Range accuracy is measured to be better than 0.05 g/cm2 .
Modulation width can be varied in steps of =0.3 g/cm2 with an accuracy of 0.05
g/cm2 or 2%. Maximum aperture diameter is 2.5 cm and maximum dose rate >32
Gy/min. Strong dependence of output on range (7%/mm) and dose rate
(0.2%/(Gy/min)) is found. Distal and lateral fall-off (80%-20%) are =0.23 and
=0.18 g/cm2 and do not depend much on range or depth. When reducing the aperture
diameter to 6 mm no significant change is observed in shape of depth-dose curve
or absolute dose (<2.5%). Measurements show a significant portion of the dose at
shallow depth (=0.7 g/cm2 ) is delivered by protons scattering off of snout
elements. Simple collimation could reduce this effect. CONCLUSION: The dosimetric
and positioning properties of the IBA ocular proton system are adequate to treat
ocular lesions with acceptable clinical margins. Suggested improvements include
limiting the output-dependence on range and reducing snout scatter.
PMID- 28517277
TI - SU-E-T-281: Secondary Light-Ions in Carbon-Ion Therapy: A GEANT4 Simulation of
LET and Dose Contributions.
AB - PURPOSE: The purpose of this investigation was to reveal the dosimetric
characteristics and contributions of the secondary light ions produced from
carbon-ion beams in water via a GEANT4 simulation. METHODS: GEANT4 low energy
electromagnetic physics processes were used for all ions. The hadronic
interactions of protons and neutrons are simulated using low energy elastic
interactions while inelastic scattering is simulated with a binary cascade (BIC)
model. Other inelastic light-ion interactions are being simulated through the
application of a quasi-molecular dynamics (QMD) model. A 27 liter cubic water
phantom consisting of 3000 packed rectangular detector sheets (30 cm * 30 cm *
0.1mm) was used in this simulation. A 1 mm diameter pencil beam of 1 million
incident carbon-ions was used in all simulations presented. The incident energies
per nucleon of the carbon beams studied were selected 155 MeV, 262 MeV and 369
MeV. The energy deposition, total kinetic energy, fluence, and dose averaged LET
of each secondary particle produced within each detection sheet was determined to
study their variations with depth. The particles investigated were gamma,
neutron, electron, positron, proton, deuteron, triton, alpha, He- 3, Li-6, Li-7,
Be-7, Be-9, Be-10, B-10, B-1 1, C-1 1, C-12, C-13, C-14, N-13, N-14, N-15, O-16.
RESULTS: The relative dose contributions of four secondary ions (B-11, C-1 1,
Alpha and Proton) were found to be each greater than 1%. The highest dose
averaged LET value was from N-13, though its averaged dose contribution was less
than 5*10-4 %. CONCLUSIONS: The secondary particles contribute small portion to
the total dose deposited from primary carbon beam. Though heavier ions (N, O)
show significant higher LET values, their relative dose contributions were
negligible.
PMID- 28517278
TI - SU-E-T-303: Practical Considerations for Maximizing Heat Production in Novel
Thermo-Brachytherapy Seed Prototype.
AB - PURPOSE: Our recently proposed thermo-brachytherapy seed offers a convenient
approach to radiation sensitization with heat in treatment of solid tumors
through concurrent administration of hyperthermia and brachytherapy. The seed
consists of a titanium capsule, containing radioactive I-125 and a ferromagnetic
core, serving as a source of self-regulating hyperthermia when placed in an
alternating electromagnetic field. We present an experimental study of the
magnetic properties of ferromagnetic Ni-Cu alloy, and develop a protocol for
obtaining the material capable of the maximum heat generation. Based on the
practically achievable temperature interval we evaluate the effect of thermal
expansion on the seed components during the hyperthermia treatment. METHODS:
Alloy samples of Ni1-xCux (0.28= * =0.3) were prepared by arc melting method in
argon atmosphere. The ingots were annealed in vacuum at 1000 degrees C for 12
hours. These samples were cut into pieces and used for magnetization measurements
with SQUID magnetometer. The thermal expansion along greatest dimension of each
component of the purposed seed was estimatedfor temperature increase from 37 to
60 EsC. RESULTS: The annealed samples show sharp Curie transition at temperature
TC~50 degrees C, varying with the alloy concentration. However, the un-annealed
sample does not show the clear transition, thus indicating a strong influence of
thermal treatments on the magnetic properties of the Ni-Cu alloy. The annealing
favors atomic diffusion, and leads a sample homogenization, minimizing
composition fluctuations and maximizing the heat generation. The effect of the
temperature rise on the thermal expansion of each component of the seed was found
to be negligible. CONCLUSIONS: We have established the thermal annealing protocol
resulting in the maximum heat generation from the Ni- Cu alloy core. The
negligible change in dimensions of the seed components due to heating assures the
safety of the implementation of thermo-brachytherapy seed for hyperthermia
treatments. This project is supported through NIH grant # 1 R41 CA153681-01A1.
PMID- 28517279
TI - SU-E-T-316: New Design of the Valencia Applicators to Reduce Radiation Leakage.
AB - PURPOSE: The Valencia applicators are designed to treat skin lesions with the
microSelectron-HDR afterloader. Although the radiation is highly directed to the
treatment area, radiation might leak through the backside of the applicator.
Recently, the manufacturer has introduced a new applicator design to reduce such
radiation leakage. This new design consists mainly in the addition of about 4 mm
of tungsten in the backside of the applicator making it thicker. The purpose of
this study is to evaluate by means of the Monte Carlo method the radiation
leakage of this new design and to evaluate whether this modification affects the
dose rate distributions in the treatment area. METHODS: The complete geometry of
the new applicators has been introduced in the Monte Carlo code GEANT4. The
applicators have been located on the surface of a cylindrical water phantom
following a methodology similar to the used in the original study of the Valencia
applicators by Granero et al [Med.Phys 2008;35:495-503]. Kerma in the water
phantom and kerma in air outside the phantom have been evaluated to estimate the
radiation leakage of the new designed Valencia applicators. RESULTS: The Monte
Carlo simulations of the new applicators show that the radiation leakage has been
reduced significantly from the previous design. The largest radiation leakage of
this design is now about 30% of the dose at the prescription point and about 10%
at 1 cm from the backside of the applicators. The dose rate distributions in the
area of treatment have not changed. CONCLUSIONS: In this study the radiation
leakage of the new design of the Valencia applicators has been obtained. The
radiation leakages have been largely reduced from the previous design without
compromising dose rate distributions in the treatment area.
PMID- 28517280
TI - SU-E-T-283: Carbon Ion Therapy Innovations in Dosimetry and Dose Delivery.
AB - OBJECTIVE: Carbon ion particle therapy delivers sharp Bragg's peaks, and hence
can produce dose delivery of very high precision and conformality. To complement
this characteristic, particle therapy centers implement a number of technologies
unique to these centers, and are not commonly known to the medical physics
community. This work outlines these adopted technologies. METHODS: Particle
therapy centers develop technologies to meet the needs of patient safety, dose
delivery accuracy, and imaging requirements complementing these state-of-the-art
centers. Through the use of literature reviews and publicly available documents,
we produced a compilation of some of these innovations, a number of them unique
to the centers themselves. RESULTS: The centers based in Bloomington, USA, Chiba,
Japan, Harima Japan, Gunma, Japan, Heidelberg, Germany, and Pavia, Italy were
reviewed. Interestingly, 60% of centers reviewed developed in-house innovations
to address the needs of particle therapy, and all but one had at least one
technology unique to its center. For example, Bloomington's MPRI developed a 3D
dosimeter used in particle beam measurement. The patient couch systems
implemented in Chiba, Japan and now Gunma, Japan are unique to the centers.
Heidelberg's HIT developed the world's first carbon ion gantry. Italy's CNAO has
a unique patient positioning system. CONCLUSIONS: Particle therapy centers,
despite being at the forefront of technology in delivering radiation to patients,
have not widely disclosed treatment delivery strategies and dosimetry techniques,
despite the material being potentially useful to the radiotherapy community. This
work is an effort in comparing and contrasting these innovations.
PMID- 28517281
TI - SU-E-T-305: Limitations of Using DICOM Data for BrachyVision Treatment Plan
Evaluation.
AB - PURPOSE: To evaluate the accuracy of a real-time automated method of performing
dosimetric quality assurance using Eclipse DICOM files for patients receiving HDR
brachytherapy and IMRT. METHODS: GYN patients are treated with concurrent high
dose rate brachtherapy and IMRT. The dosimetric parameters were obtained through
an in-house QA program developed using Matlab. The DICOM files containing DVH
data for organsat-risk (OAR) were analyzed Dosimetric data for 7 patients (total
42 fractions) were collected for bladder, rectum and sigmoid. The accuracy of the
dosimetric parameters was estimated by comparing the parameters obtained from the
DICOM based QA program and those in BrachyVision. RESULTS: The maximal dose
values (Dmax) for the OARs obtained using the DICOM-based program are
significantly smaller than those valued reported in BrachyVision by 36.2%-48.3%.
The mean dose has a deviation from 1% - 2.4%. The dose for the volume of 2cc
(D2cc) has a difference up to 7.6% for structures with the volume larger than 200
cc. The average difference of D2cc is 0.5% for structures less than 200 cc. We
found that Eclipse BrachyVision only exports DVH data down to a volume equivalent
to 1% of the maximum volume for a given structure. Therefore, the reported
maximal dose values obtained from DICOM RT dose file do not accurately reflect
the maximum dose in a treatment plan. This will also slightly affect the mean
dose calculation and D2cc when the structure volume is larger than 200cc.
CONCLUSIONS: The automatic QA tool based on DICOM files provides a quick
retrieval of dose to organs-at-risk and coverage of targets. However, maximal
dose to structures is not accurate due to the truncationof the DVH information
contained in DICOM files.
PMID- 28517282
TI - SU-E-T-320: A New Verification Phantom for GYN Brachytherapy Applicators Using
GafChromic - Films.
AB - PURPOSE: Brachytherapy plays an important role in radiation therapy a wide range
of tumor sits such as vaginal, cervical and endometrial cancers. The purpose of
this project was to design, fabricate and verify a new phantom for dosimetric
verification at small distances from GYN applicators used with GZP6 cobalt-60 HDR
system. METHODS: A new phantom has been designed and fabricated from 90 slabs of
18*16*0.2 cm3 Perspex to accommodate one tandem and two ovoids. The thin layer of
the slabs was chosen to place GafChromic films in between the slabs for dosimetry
with GZP6 cobalt-60 HDR system. For verification of this device, an assembly
composed of a large ovoid size (3cm diameter) and tandem #1 with the least
curvature was selected in this study. With this assembly, GafChromic films were
exposed using a plan with 500 cGy dose delivery to point "A". The irradiated
films were scanned. The responses of the films were converted to dose by
calibrating samples of these films using a cobalt-60 teletherapy system in the
range of 25 to 800 cGy dose. The measured isodose curves with the films were
compared to calculated isodose lines by the treatment planning software. RESULTS:
The Result of these investigations indicated differences of up to +/- 23 %
between the planning and measured dosimetry at different points in GYN implant
with cobalt-60 HDR source of GZP6 system. Therefore, this phantom enabled us to
confirm the accuracy of radiation delivery to the GYN patients with cobalt-60 HDR
source of GZP6 system. CONCLUSIONS: The new phantom design could be utilized for
the QA procedure of the GZP6 cobalt-60 HDR system as well as the Ir-192 HDR
system to confirmation the accuracy of dose distribution in GYN implants,
especially in non-traditional implants. The Radiotherapy Department of Shahid
Beheshti University at Shohada hospital sponsored the purchase of the phantom
materials and films used in the investigations.
PMID- 28517283
TI - SU-E-T-266: Shielding Measurements for a Proton Therapy Facility.
AB - PURPOSE: This paper is a follow up on the analytical calculations for the Roberts
Proton Therapy Center with empirical data to determine the precision of the
calculations from Avery, et al. METHODS: Neutrak dosimeters were placed in two
sets around the facility while it was in operation at points of interest examined
in Avery, et al. The doses to these dosimeters were recorded over one month for
one set and two months for the other. Dosimeters that both recorded a dose and
could be practically examined were compared to the doses predicted via the
analytical method of Avery, et al. at their point of placement. RESULTS: Two
points showed a less than 10% difference to the calculated doses. One point
shielded by both concrete and pre-cast blocks and one point shielded by both
concrete and the facility's cyclotron were not as precise. CONCLUSIONS: The
analytical calculation method explored in Avery, et al. is fairly precise in
describing the dose at various points in the facility shielded only by concrete.
for materials other than concrete, such as the make-up of the cyclotron or
varying wall material, it warrants follow up calculations using the same method.
PMID- 28517284
TI - SU-E-T-296: Optimization of the Energy Selection System with Varying Magnetic
Field for Laser-Accelerated Proton Beams.
AB - PURPOSE: Laser-based accelerated proton beams are unsuitable for clinical use
because of their broad energy spectra. For this reason, it is essential to employ
an energy selection system (ESS). The purpose of this study is to determine
optimum parameters of the ESS which uses a varying magnetic field to generate
Bragg-peak. METHODS: We simulated an accelerated proton beams using radiation
pressure acceleration mechanism with carbon-proton mixture target. The density
ratio (n = 6) between the protons and the carbon ions is one of optimization
parameters in determining the accelerating mechanisms. The ESS was implemented by
the Geant4 Monte Carlo toolkit. In order to optimize the hole size and position
of the energy selection collimator, and magnetic field at ESS, these parameters
were simulated for acquiring energy and dose distributions by changing each
values. RESULTS: The proton energy distributions had a poly-energetic
distribution after passing through the ESS. As the magnetic field was increased,
the mean energy of the proton beams also was increased. Also as the hole size was
increased, the energy bandwidth of proton passed through the ESS was increased.
The hole size and position of the energy selection collimator were effectively
optimized to 2 cm and 5 cm from the z-axis, respectively. CONCLUSIONS: We
simulated laser-accelerated proton beams using ESS for generation of Bragg-peak.
Our results suggest that the ESS with magnetic field variation can effectively
generate a Bragg-peak suitable for use in proton radiation therapy. Our ESS can
be applied to pencil beam scanning proton therapy.
PMID- 28517286
TI - SU-E-T-287: Patterns of Patient Specific Dosimetry in Total Body Irradiation.
AB - PURPOSE: Total body irradiation (TBI) is commonly used for conditioning prior to
transplant in hematologic and immunologic diseases. Due to variability in body
thickness, achieving dose uniformity across body within +/-10% of the prescribed
dose is challenging. The dose uniformity is further complicated by, techniques
and beam energy used, lung shielding and selection of detector. The translational
table technique for TBI could compensate for estimated delivered dose to whole
body by adjusting couch speed during treatment. However, it is difficult to
accurately estimate the dose by calculation and hence in vivo dosimetry (IVD) is
routinely performed for TBI. The patterns of patient specific dosimetry, IVD are
presented in this study. METHODS: Under IRB exempt status, 161 patients who
received TBI treatment between 2006 and 2011 were retrospectively analyzed using
the treatment records from Cobalt-60 teletherapy unit and translational treatment
couch. During treatment, IVD detectors (TLD, diode, or MOSFET) were placed on
patient surface; both entrance and exit dose were recorded at the patient's head,
neck, mediastinum, umbilicus, and knee. When large differences between prescribed
and measured dose were observed, the dose delivery was corrected for subsequent
fractions by adjustment in couch speed and/or bolus placement. RESULTS: Across
the entire cohort, the mean (range) percent variance between calculated and
measured dose were -2.3% (-66.2 - 35.3), 1.1% (-62.2 - 40.3), -1.9% (-66.4 -
46.6), -1.1% (-35.2 - 42.9), and 3.4% (-47.9 - 108.5) for head, neck,
mediastinum, umbilicus, and knee, respectively. When the dose differences for
multiple fractions were averaged, the compliance (+/-10%) between prescription
and measured dose was improved as at umbilicus from 83.9% to 98.5%. CONCLUSIONS:
Actual dose measurement analysis of TBI patients reveals a potentially wide
variance from calculated dose. Dose uniformity can be significantly improved with
immediate feedback after the first fraction prior to subsequent treatments. This
work was supported by the JSPS Core-to-Core Program No. 23003.
PMID- 28517285
TI - SU-E-T-276: Treatment Planning Strategies for Lung Injury Studies in Rat Models
in 6 MV Delivery.
AB - PURPOSE: To study planning strategies that can be used in small animal radiation
induced lung toxicity experiments using 6 MV accelerator with high density MLC.
METHODS: Three different types of plans were designed on CT images of a Sprague
Dawley rat model to irradiate 50% of the total lung volume (lung divided into
apex and base) with a prescription dose of 24 Gy to the partial lung. Two VMAT
arc therapy plans were optimized to cover to the prescription dose, either the
apex or base of the lung. Two AP- PA plans were designed to completely block
either lung apex or base while irradiating the remaining 50% of the lung.
Finally, two AP-PA plans were designed to cover, to the prescription dose, the
apex or base of the lung. The plans were designed and optimized using the Eclipse
AAA algorithm and recalculated using the MMCTP/EGS/Beam Monte Carlo system.
RESULTS: When completely blocking the lung base, the apex will be underdosed by
up to 30%; when completely covering the apex by the prescribed dose, the base
will receive overdosing (V50%=73%). The VMAT plan leads to a more conformal dose
distribution and spares unnecessary skin exposure when compared to AP-PA MV or kV
delivery. Despite the small size of rat model, the 6 MV VMAT delivery is superior
in terms of dose conformality and sparing of the heart and the non-irradiated 50%
of the lung compared to the standard, simpler, AP-PA delivery. MC dosimetry in
lung shows that the delivered dose is 10% higher than predicted by AAA because of
the predominance of small fields in the delivery. CONCLUSIONS: Clinical state-of-
the-art planning and delivery techniques can be scaled down accurately to rats.
The use of these techniques is essential in small animal studies to render
conclusions of radiation response investigations translatable to human studies.
PMID- 28517287
TI - SU-E-T-309: Dosimetric Study and Clinical Implementation of an HDR Applicator of
SAVI for Partial Breast Irradiation.
AB - PURPOSE: To present clinical implementation and quality assurance for a new HDR
applicator of Strut-Adjusted Volume Implant (SAVI) for partial breast irradiation
and the higher-order DVH examined. METHODS: The SAVI applicator with multi
peripheral struts can be differentially loaded with the HDR source for a
conformal dose distribution to the lumpectomy cavity. The treatment plan is
evaluated by a dose volume histogram (DVH) as follows: V90 > 90%, V150 < 50 cc,
and V200 < 20 cc. A higher-order DVH which may reflect radiation-induced
toxicity, such as V300, was studied. The SAVI device status was verified by the
3D CT images and image fusion. Tissue invagination was investigated using an ion
chamber and film with the cavity filled with air and water merged into a water
phantom. RESULTS: Twenty-nine patients to date at Mercy Medical Center,
Baltimore, Maryland were treated with SAVI device. The dosimetric data
demonstrated the achievements of greater than 90% coverage for V90 at 96.8% and
94.1% for V95 while keeping a low V150 at 33.9 cc and V200 at 16.5 cc. V300 was
found to be 2.7 cc in average. Potential uncertainties introduced by the SAVI
applicator motion were a 3% variation in dose caused either by a 3-mm}
translation or a rotation of 3 degree. CONCLUSIONS: Multiple catheters of the
SAVI applicator allows for optimal and conformal dose distribution around a
lumpectomy cavity while minimizing the dose to adjacent normal structures such as
skin and ribcage. Multiple imaging techniques are capable to verify cavity
variation, strut collapse or relative motion, and device shift. A nearly fully
loaded dwell source position produced the discrepancy of less than 3% and allow
for optimal and conformal dose distribution to a lumpectomy cavity. Advantages of
the SAVI applicator have been shown in treating breast cancer with the shallower,
elliptical, and asymmetric cavity.
PMID- 28517288
TI - SU-E-T-270: Optimized Shielding Calculations for Medical Linear Accelerators
(LINACs).
AB - PURPOSE: The purpose of radiation shielding is to reduce the effective equivalent
dose from a medical linear accelerator (LINAC) to a point outside the room to a
level determined by individual state/international regulations. The study was
performed to design LINAC's room for newly planned radiotherapy centers. METHODS:
Optimized shielding calculations were performed for LINACs having maximum photon
energy of 20 MV based on NCRP 151. The maximum permissible dose limits were kept
0.04 mSv/week and 0.002 mSv/week for controlled and uncontrolled areas
respectively by following ALARA principle. The planned LINAC's room was compared
to the already constructed (non-optimized) LINAC's room to evaluate the shielding
costs and the other facilities those are directly related to the room design.
RESULTS: In the evaluation process it was noted that the non-optimized room size
(i.e., 610 * 610 cm2 or 20 feet * 20 feet) is not suitable for total body
irradiation (TBI) although the machine installed inside was having not only the
facility of TBI but the license was acquired. By keeping this point in view, the
optimized INAC's room size was kept 762 * 762 cm 2. Although, the area of the
optimized rooms was greater than the non-planned room (i.e., 762 * 762 cm 2
instead of 610 * 610 cm 2), the shielding cost for the optimized LINAC's rooms
was reduced by 15%. When optimized shielding calculations were re-performed for
non-optimized shielding room (i.e., keeping room size, occupancy factors,
workload etc. same), it was found that the shielding cost may be lower to 41 %.
CONCLUSIONS: In conclusion, non- optimized LINAC's room can not only put extra
financial burden on the hospital but also can cause of some serious issues
related to providing health care facilities for patients.
PMID- 28517289
TI - SU-E-T-280: Optimal Angle for a Dual-Field Stanford Technique for TSET.
AB - PURPOSE: This study examines the optimal angle for a dual-field Stanford
technique for TSET at extended SSD (SSD= 1, 2, 3, 4, 5 m) to predict a readily
available optimal angle for any SSD. METHODS: The optimal angle at various SSDs
is found using detector array. The diode array consists of 9 diodes placed on a
vertical board with a measured vertical scale with the origin placed at
isocenter. The lateral distance ranges from -100 to +75 cm. A square 36*36 cm2
field is used to deliver dose in HDTSe- delivery mode with a dose rate 2500
MU/min from a Varian Clinic 2300IX linac. Several pairs of gantry angles for the
dual field are used, with the first gantry being 70 degrees -78 degrees and the
second being 110 degrees -102 degrees . These Result in a dual field of 90
degrees +/- theta (theta = 10 degrees - 20 degrees ) to build a suitable
flatness profile on the vertical axis for treatment. The best group is chosen to
determine the optimal angle for each SSD considered. From these optimal angles,
an algorithm is determined for any extended SSD treatment. RESULTS: It is found
that the optimal angle for TSET does change as one varies the SSD. These angle
groups are specific for each SSD giving definite markers for the algorithm. At an
SSD of 5 m it has been shown that an optimal angle of theta = 106 degrees
produces the best flatness on the vertical axis. While at SSD of 4 m, 9 = 18
degrees Conclusions: An algorithm can now be applied for any treatment center
considering a dual- field Stanford technique for TSET simplifying the physics
commissioning process for the center in consideration.
PMID- 28517290
TI - SU-E-T-302: A Simulation Study with Geant4 Investigating the Secondary Prompt
Gamma Emissions from Incident 40 MeV Protons Onto Various Materials.
AB - PURPOSE: This study aims to investigate the prompt secondary gamma spectrum and
thedepth-dose distributions of incident 40 MeV protons onto various phantom
materials.The goal is to find a relationship between the secondary prompt gamma
emissions andthe range of the incident particles. METHODS: An application was
constructed using the Geant4 Monte CarloToolkit utilizing various physics
packages. Several phantom materials were irradiatedwith a pencil beam of 40 MeV
protons. These materials include PMMA (C5H8O2,density 1.18 g/cm3 ) and the built
in Geant4 materials bone, soft-tissue, and water. Foreach simulation, the energy
deposited from the incident proton was recorded every 1 mmincrement of depth in
the phantom. The resulting prompt secondary gamma emissionswere recorded from 0
to 10 MeV in energy bins of 10 keV. RESULTS: The secondary prompt gamma spectrum
has various peaks. The peaks locatedabout 4.4 and 6 MeV correspond to the carbon
and oxygen de-excitation photons,respectively. Our simulations show greater
production of the higher-energy gammaparticles closer to the Bragg-Peak. When we
plot the oxygen peak against the normalizedBragg-Peak we found that in all
materials the difference between Bragg-Peak and theoxygen de-excitation photon
peak to be about 2 mm. The oxygen peak could be used inthe clinic for range
verification of the incident proton beam. CONCLUSIONS: Our Geant4 Monte Carlo
application was used to investigate the secondaryprompt gamma emissions from
incident 40 MeV protons. A relationship was betweenthe 6 MeV peak and the
incident proton Bragg Peak. We believe that prominent peaksaround 4 and 6 MeV can
be used to locate the range of the incident beam provided adetector system is
built that can count these high-energy gamma particles.
PMID- 28517291
TI - SU-E-T-291: Dosimetry of Double Scattered Proton Beam Fields Used for Cranio
Spinal Irradiation.
AB - PURPOSE: To investigate the effect of source to surface distance on treatment
field lateral penumbra width and the consequence of setup error on the dose
distribution in the junction between two spinal fields of double scattered proton
beams. METHODS: The CT images of the Spine Phantom from Radiological Physics
Center was used to design a double scattered proton beam treatment plan using
Varian Eclipse treatment planning system. PTV included spinal cord, vertebral
body and part of spinous process. The PTV was divided into superior and inferior
parts and two posterior fields were used to cover the targets with the prescribed
dose. 2D dose was measured using IBA MatriXX and EBT2 film at a depth close to
the center of SOBPs of both the fields located both at the nominal source to axis
distance (SAD) of 270 cm and at an extended SAD. The field separation was changed
by +/-1 mm to study the effect of setup error. The measured and TPS calculated
dose distributions in verification plans in a water phantom were compared.
RESULTS: The measured 2-D doses agreed very well with planned ones for individual
fields. 99% of pixels pass 3%/3 mm dose/distance agreement criteria. The CAX dose
differences are within 2%. The 80% to 20% penumbra widths at nominal SAD are
7.4/7.7/7.8 mm for planned/MatriXX/EBT2 film respectively, and about 1 mm wider
for the extended SAD. The measured maximum dose was about 10% higher than that
from the plan, and decreased/increased about 7% when the fields were separated by
+/-1 mm. CONCLUSIONS: The penumbra width is modestly affected by the extended SSD
often used for patient treatment. Dose in the junction of two fields is very
sensitive to the setup error and the accuracy of the TPS dose calculation in this
region may be limited.
PMID- 28517293
TI - SU-E-T-282: Preliminary Simulation Study for 3 Dimensional Dose Delivery in
Carbon Beam Active Scanning System of KHIMA.
AB - PURPOSE: KHIMA (Korea Heavy Ion Medical Accelerator) project has a plan to
develop and construct a research beam line for carbon beam active scanning
system. The carbon beam line consists with scanning magnet, beam-monitoring
system, energy modulation system. In this study, the significant components,
scanning magnets and ridge filter, were designed for the carbon beam active
scanning beam line. METHODS: The designed scanning magnet and ridge filter were
used for 3 dimensional active beam dose delivery simulation by Geant4 Monte Carlo
code. The target volume of the active scanning was 10 * 10 * 5 cm2 on the water
phantom with 400 MeV/u of carbon beam. The transvers plane on the target was
scanned by 3mm of step size. And, the optimized weighting factors of transverse
scanning were obtained by MINUIT fitting package of ROOT. An aluminum ridge
filter was designed to generate 5 cm of physical SOBP through step shape, which
was optimized through in-house iteration method and the MINUIT package.The
simulation was performed with Geant4 through applying the transverse scanning
with the obtained weighting factor and the designed ridge filter. RESULTS: The
uniformity on the transverse plan will be expected below 4% when it considered
scattered beam. Also, the uniformity for longitudinal plane will be expected
lower then 5%. CONCLUSIONS: This preliminary computational study was shown a
possibility of using ridge filter for acceptable 3 dimensional uniformity on
active beam delivery system in carbon beam therapy line. The optimization process
to reach an acceptable uniformity on clinical use should be followed. In
addition, it would be used for the design of treatment planning system software
for KIHMA project.
PMID- 28517292
TI - SU-E-T-313: Probe-Type Experimental Dosimetry in Terms of Absorbed Dose to Water
in Photon-Brachytherapy a Proposal for a Radiation-Quality Index.
AB - PURPOSE: In photon-brachytherapy (BT), all data for clinical dosimetry (e.g., the
dose-rate constant) are not measured in water, but calculated, based on MC
simulation. To enable the measurement of absorbed dose to water, DW, in the
vicinity of a source, the complex energy-dependence and other influence
quantities must be considered. METHODS: The detectors response, R=M/D, is
understood as product of a detector-material dependent 'absorbed dose response',
Ren, and Rin, the 'intrinsic response'. Ren is described by the Burlin-theory and
because of dissimilarities between the detector-material and water, will have
energy dependent correction factors which convert Ren into the clinically
relevant DW,Qo=MQo * ND,W,Qo. To characterize BT- source-types, we propose a new
'radiation-quality index' QBT=Dprim(2cm)/Dprim(1cm), the ratio of the primary
dose to water at r=2cm to that at the reference distance r=1cm, similar to
external beam dosimetry. Although QBT cannot be measured directly, it can be
derived from primary and scatter separated dose-data, published as consensus data
e.g., in the Carlton AAPM-TG-43-database. RESULTS: Mean QBT-values are: for nine
HDR and four PDR 192Ir-sources: 0.2258+/-0.5%; one 169Yb- source: 0.2142; and one
125I-source: 0.1544. CONCLUSIONS: The main benefit of this new QBT-concept is
that a type of BT-dosimetry-detector needs to be calibrated only for one
reference radiation-quality, e.g., for Q0=192Ir. To measure the dose for
different source-types, DW can be determined using calculated radiation-quality
conversion factors kQ,QoBT, to be included in the AAPM-database and to be
provided by the manufacturer for each detector-type. Typical BT-dosimetry
detectors are plastic scintillation detectors, radiochromic film,
thermoluminescence detectors, optically stimulated detectors, and small volume
ionization chambers. Recently, different DW(1cm)-primary standards have been
developed in several European NMIs, enabling to calibrate BT-radiation- sources
and BT-dosimetry-detectors and allowing to verify MC-calculated dose-rate
constant values. The proposed definition of QBT has to be discussed
internationally to find broad consensus.
PMID- 28517294
TI - SU-E-T-304: Evaluation of Mammosite Multi-Lumen Rotation and Its Dosimetric
Consequences.
AB - PURPOSE: To evaluate the dosimetric impact of MammoSite Multi-Lumen (MSML)
rotation in phantom and patient studies. METHODS AND MATERIALS: A MSML phantom
with an asymmetric dose distribution was created. Target volume coverage and dose
at a fixed point 1 cm from the MSML were evaluated as functions of rotation about
three orthogonal axes (where the origin was set at the center of the MSML and
axis one ran along the central catheter). Additionally, for three MSML patients
that were set-up by aligning the stem of the MSML to skin marks, CT scans were
acquired before each fraction. Rotation about three axes and maximum point dose
to skin and chestwall were evaluated. RESULTS: In phantom, 10 degrees rotations
about the central, second, and third axes give average absolute point dose
changes with respect to the maximum dose of 1.9%, 3.7%, and 4.2%, respectively;
and changes in PTV coverage of 0.9%, 1.0%., and 0.8%, respectively. For patients
1-3 the average absolute rotation about the central axis was 13.60, 9.50, and
7.20, respectively; axis two was 7.00, 3.20, and 11.40, respectively; axis three
was 2.90, 2.90, and 3.80, respectively. For cases 1-3 the average absolute change
per fraction in maximum point dose to the skin was 0.29 Gy, 0.14 Gy, and 0.39 Gy,
respectively; to the chestwall was 0.17 Gy, 0.20 Gy, and 0.21 Gy, respectively.
CONCLUSION: Phantom studies showed change in point dose and PTV coverage for a 10
degrees rotation about the central catheter yields < 2% variance. Patient data
indicates skin mark alignment is capable of positioning the MSML with 10 degrees
accuracy about the central axis. Thus, central axis rotation can be adequately
accounted for by skin mark alignment. However, review of the patient data shows
that rotations about the other axes are equally important and should be
considered and managed.
PMID- 28517295
TI - SU-E-T-293: The Potential Application of High Energy Proton Beam-Induced Positron
for PET Imaging Technique.
AB - PURPOSE: An existing nuclear interaction cross-section of a positron emitter was
used to predict range accuracy of proton beams and cross section of the positron
emitters detected by the PET scanner Methods: To achieve this goal, a MLIC
phantom was irradiated to 2Gy dose using 124.61MeV, 143.08MeV and 155.25MeV
proton beam corresponding to the depths of 6.88cm, 10cm and 16cm, respectively,
in the phantom. The activity produced in each phantom was examined by PET scanner
within a couple of minutes post-irradiation. Hence, activity signal produced
along the activated depth dose profile was recorded. In this project, the isotope
production cross section for carbon from Landolt-Bornstein (1973) has been
utilized. RESULTS: A good correlation (about 95%) between the positron emission
and the isotope cross section of the carbon was observed. Consistency between the
induced activity and the carbon isotope cross section occurred mainly at the
distal aspect of the fall off zone of both relative cross-sections (i.e. between
60 - 100%). These results were obtained using the high relative abundance of
carbon (i.e. 70%) in the phantoms.Conclusions The ranges measured by the depth
dose profiles and positron emission profiles were in good agreement at the distal
fall off edge. Furthermore, it is confirmed that the interaction cross-sections
of individual elements in the tissues could be used to determine the range
accuracy of the proton depth dose profiles. None Applicable.
PMID- 28517296
TI - SU-E-T-319: Monte Carlo Characterization of a New Directional Pd-103 High Dose
Rate Source for Brachytherapy Application.
AB - PURPOSE: Standard brachytherapy sources emit radiation in a non-preferential
direction away from the source. Though treatment outcomes are good, this can lead
to late skin and subcutaneous toxicities in sensitive structures. Proposed low
dose rate directional sources for interstitial brachytherapy, showed to have an
improvement in the dose uniformity within the subcutaneous volume, reduction in
skin dose, and reduction in volume receiving dose outside the target. The
objective of this work is to demonstrate the potential use of a new Pd-103
directional seed for application in high dose rate brachytherapy treatments.
METHODS: Monte Carlo simulations were performed using the MCNP5 F6 energy
deposition tallies as well as the MCNP5 F4 flux density tallies placed around a
partially shielded Pd-103 source at angles(deg): 0, 45, 90, 135, 180, 225, 270,
315 as well as radial distances (cm): 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10.
The source that modeled was a Pd-103 core using TG-43U recommended nuclear data,
with a diameter = 1.4 mm, active length = 1.0 cm. In addition osmium metal with
.03 mm thickness was used as shielding material to cover half of the cylindrical
surface of the Pd-103 volume. The seed was encapsulated using .05 mm thick
titanium. RESULTS: MCNP models show that the dose to the radial distances,
corresponding to the osmium shielded side, are dramatically reduced to less than
4% of the total dose. CONCLUSIONS: The potential of a Pd-103 directional
brachytherapy source has been studied. The results show that a seed with a
partially shielded volume can be exploited to reduce side effects associated with
radiation therapy to sensitive structures surrounding target volumes.
PMID- 28517297
TI - SU-E-T-265: Reducing Pacemaker Doses with a Lead Sheet: A Multi-Detector Study.
AB - PURPOSE: Evaluate the usability of lead shielding to reduce the dose to
pacemakers. The efficiency and risk of this type of skin block will be presented.
METHODS: A solid water phantom was used and all measurements were made at a depth
of 0.5 cm for 6 MV and 23 MV photon beams. Measurements were performed with a
parallel plate ion chamber and with a plastic scintillation detector (PSD)
prototype. Measurements were made for fields of 10, 20 and 30 cm square. For
every field, measurements were made in increment of 5 cm from the center of the
field to the edge of the 60 cm long phantom for anterior and posterior beams. All
measures have been made with and without a 1.6 mm of lead shielding wrapped in a
thermoplastic. RESULTS: For all measurements, both detectors agree to 0.6%, well
within the uncertainties of the detectors. With antero-posterior fields, the
benefit of shielding is more important at 23MV (reduction of dose by65%) compared
to 6MV (reduction of dose by 46%) when the shielding is out of the field. For
distances larger than 35 cm, no benefits are measured. In the case were the lead
is completely inside the fields, the dose is increased by the presence of
shielding. The same observation is made for postero-anterior fields. For
shielding out of field, the dose is slightly increased. CONCLUSIONS: The used of
lead shielding with antero-posterior field is advised and provided an easy way to
decrease dose to pacemaker. For a postero-anterior field, it is preferable to
avoid shielding, but it could be used if it stays outside fields in the case of a
multiple beams treatment. PSD has been shown to be an excellent candidate for in
vivo monitoring dose to pacemakers and also site like foetus.
PMID- 28517298
TI - SU-E-T-275: Dose Verification in a Small Animal Image-Guided Radiation Therapy X
Ray Machine: A Dose Comparison between TG-61 Based Look-Up Table and MOSFET
Method for Various Collimator Sizes.
AB - PURPOSE: To verify the accuracy of TG-61 based dosimetry with MOSFET technology
using a tissue-equivalent mouse phantom. METHODS: Accuracy of mouse dose between
a TG-61 based look-up table was verified with MOSFET technology. The look-up
table followed a TG-61 based commissioning and used a solid water block and
radiochromic film. A tissue-equivalent mouse phantom (2 cm diameter, 8 cm length)
was used for the MOSFET method. Detectors were placed in the phantom at the head
and center of the body. MOSFETs were calibrated in air with an ion chamber and f
factor was applied to derive the dose to tissue. In CBCT mode, the phantom was
positioned such that the system isocenter coincided with the center of the MOSFET
with the active volume perpendicular to the beam. The absorbed dose was measured
three times for seven different collimators, respectively. The exposure
parameters were 225 kVp, 13 mA, and an exposure time of 20 s. RESULTS: For a 10
mm, 15 mm, and 20 mm circular collimator, the dose measured by the phantom was
4.3%, 2.7%, and 6% lower than TG-61 based measurements, respectively. For a 10 *
10 mm, 20 * 20 mm, and 40 * 40 mm collimator, the dose difference was 4.7%, 7.7%,
and 2.9%, respectively. CONCLUSIONS: The MOSFET data was systematically lower
than the commissioning data. The dose difference is due to the increased scatter
radiation in the solid water block versus the dimension of the mouse phantom
leading to an overestimation of the actual dose in the solid water block. The
MOSFET method with the use of a tissue- equivalent mouse phantom provides less
labor intensive geometry-specific dosimetry and accuracy with better dose
tolerances of up to +/- 2.7%.
PMID- 28517299
TI - SU-E-T-308: Dosimetry of a New Minimally Invasive Episcleral Brachytherapy
Device.
AB - PURPOSE: Describe the dosimetry of an episcleral brachytherapy device. METHODS:
The SMD-I device is designed to treat exudative age-related macular degeneration
(AMD) and employs a Sr-90/Y-90 source encapsulated in a stainless steel cylinder.
The source is welded to a flexible wire allowing it to travel from a shielded
vault in the SMD-I handle to the distal end of a curved cannula to deliver a
therapeutic dose of radiation through the sclera to the neovascular target in the
subchoroidal space. The SMD-I handle and vault are comprised of Ultem, a
lightweight radiation tolerant plastic, which shields the surgeon. Dose
calculations were performed using the MCNPX radiation transport code. The
absolute dose rate was determined using radiochromic film (GAFChromatic(c) MD-55)
at a point in solid water 2.0mm from the source center perpendicular to the
cannula. Dose rates at several depths were measured using Kodak EDR2 film in
water equivalent phantoms to compare with the absolute dose rate measurement and
MCNPX calculations. The surgeon's hand dose received while manipulating the
device with the source in the vault was measured using standard TL
(thermoluminescence) finger ring dosimeters, TL ChipstratesTM, and calculated
with MCNPX. RESULTS: The absolute dose rate 2.0mm from the source center is 0.45
Gy/min/mCi. The EDR2 film results agree with the absolute dose measurement and
the MCNPX calculations. The dose rate decreases rapidly with depth so that the
dose at the target depth (3mm) is approximately 8 times less than at 1mm depth
(sclera). The dose distribution is sensitive to the angle between the cannula and
the neovascular plane. Both TL methods yield a maximum dose rate of 6 MUSv/min
mCi to the surgeon's fingers consistent with the MCNPX calculation. CONCLUSIONS:
The SMD-I device permits accurate delivery of a therapeutic radiation dose for
the treatment of exudative AMD. Russell J. Hamilton is a founder and currently
serves on the Scientific Advisory Board of Salutaris Medical Devices, Inc.
Wendell Lutz and Thomas Cetas serve on the Scientific Advisory Board of Salutaris
Medical Devices, Inc. All authors have received financial support from Salutaris
Medical Devices, Inc.
PMID- 28517300
TI - SU-E-T-269: The Evaluation of Copper as an Alternative for Cerrobend Electron
Shielding.
AB - PURPOSE: To evaluate the replacement of Cerrobend by copper for electron beam
cutouts. METHODS: The dosimetric comparisons for circular copper-and Cerrobend
cutouts with diameters (1.0, 2.0, 3.0, 5.0, 7.5, 10.0, and 12.5 cm) were made
using electron beams with energies (6, 9, 12, 16, and 20 MeV) from 3 Varian
accelerators. A PTW Farmer chamber (0.125cc-volume) was used for larger cutouts
(diameters > 2cm), and an electron-diode for the 2 smallest cutouts. Also a
Markus parallel plate chamber was used. RESULTS: (1) The tests showed little
difference for the electron dosimetric characteristics, Eo, Eop, R50, Rp, and
dmax. For larger cutout, the parameters were virtually the same for copper and
Cerrobend. for smaller cutout (diameter = 3cm), small discrepancies were observed
i.e. differences < 1mm for R50, Rp and dmax, =0.1MeV for Eop, and =0.3MeV for Eo.
(2) The larger-cutout outputs at dmax were also virtually the same (difference =
0.6%). For smaller cutouts (diameters = 3cm), the copper outputs were 2.0%~5.0%
higher than Cerrobend. (3) For lower energy electrons (<12MeV), more larger-angle
scattered electrons from higher-Z Cerrobend raise the Cerrobend percentage-depth
dose (PDD) curve at shallow-depths, and more forward scatter dose after dmax from
lower-Z copper shifts the copper PDD slightly away from the one of Cerrobend. for
higher energy electrons (= 12MeV), the shallow-dose difference becomes smaller
for both cutouts, but even more forward-scattered dose from copper shifts
copper's PDD further away from Cerrobend's. (4) The higher X-ray transmission
through copper is also observable; i.e. 12%, 10%, and 7% for 20MeV, 16MeV, and
12MeV, respectively, but such small transmitted amount is clinically
insignificant. CONCLUSIONS: Except for a higher x-ray transmission, other
dosimetric differences brought in by the replacement of Cerrobend by copper
cutout are negligible.
PMID- 28517301
TI - SU-E-T-279: A Novel Electron-Beam Combined with Magnetic Field Application for
Radiotherapy.
AB - PURPOSE: The new beam and delivery system consists of an electron accelerator and
a system of magnets (one or more). Introducing a transverse magnetic field in and
near the tumor, causes the electrons to spiral in this region, thereby producing
an effective peak in the depth dose distribution, within the tumor volume.
Although the basic idea is not new, we suggest here for the first time, a viable
as well as a workable, magnetic field configuration, which in addition to
focusing the beam does not interfere with its propagation to the target. METHODS:
The electron accelerator: can be a linear accelerator or any other type electron
accelerator, capable of producing different electron energies for different
depths and dose absorption accumulation. The Field size can be as small as a
pencil beam and as big as any of the other standard field sizes that are used in
radiotherapy. The scatter filter can be used or removed. The dose rate
accumulation can be as higher as possible.The magnets are able to produce
magnetic fields. The order, direction, width, place, shape and number of the
magnetic fields define the shape and the Percentage Depth Dose (PDD) curve of the
electron beam. Prototypes were successfully tested by means of computer
simulation, using:COMSOL-Multiphsics for magnetic fields calculations. FLUKA
package, for electron beam MC simulation. RESULTS: Our results suggest that by
using an electron beam at different energies, combined with magnetic fields, we
could modify the delivered dose. This is caused by manipulating the electron
motion via the Lorentz force. The applied magnetic field, will focus the electron
beam at a given depth and deposit the energy in a given volume and depth, where
otherwise the electron energy will have spread deeper. The direction and
magnitude of the magnetic fields will prevent the scattering of the electron beam
and its absorption in remote volumes. In practice, we get a pseudo Bragg peak
depth dose distribution, applying a relatively low cost system. The therapeutic
efficiency induced by the system is of similar efficiency as the ion beam therapy
techniques. CONCLUSIONS: Our novel concept demonstrates treatment that is almost
similar to proton therapy and in some parameters even better performance.Unlike
the current high-energy electron therapy, our system's beam deposit almost all of
its energy on its target, with a low amount of radiation deposited in tissues
from the surface of the skin to the front of tumor, and almost no "exit dose"
beyond the tumor. This property will enables to hit tumors with higher,
potentially more effective radiation doses, while being considerably less
expensive.
PMID- 28517302
TI - SU-E-T-301: A Novel Daily QA Device for Proton Therapy.
AB - PURPOSE: We describe the design and use of a daily QA device for proton therapy.
The device is designed for therapists to check the readiness of the IBA Proton
Therapy System (IBA, Louvain-la-Neuve, Belgium) during morning QA. The checks
include connectivity, positioning, mechanical, imaging and dosimetric parameters
of the proton therapy system. METHODS: The device consists of a commercial QA
device, (rf-DailyQA3 -Sun Nuclear Corporation, Melbourne, FL), in conjunction
with a home-made acrylic phantom and mechanical indexing jig. The indexing jig
indexes the rf-DailyQA3 to treatment couch. Fiducial markers embedded in the
phantom are used for checking the x-ray image and alignment accuracy of the
imaging system (VeriSuite, MedCom, Darmstadt- Germany). The rf- DailyQA3 is used
to check the proton beam output, range and symmetry, which are acquired during
one single beam delivery of 100 monitor units. We developed in-house software to
calculate the variation of beam range and symmetry, based on readings from the
various ion chambers inside the rf-DailyQA3. RESULTS: The device has been
employed to perform daily QA since June 2010 at two operational proton treatment
centers and will soon be implemented at ProCure's New Jersey center. All QA tests
are performed by radiation therapists and reviewed by the medical physicist on
duty. Due to the simplicity of the device and the associated processing software,
the QA time is less than 20 minutes per room. The measurement data collected by
the device during daily QA are recorded in the OIS. The integrity of the data is
validated by comparing against other independent measurements. CONCLUSIONS: The
daily QA device has been proven to be robust, reliable and user-friendly. The
performance of this system has been proven to be stable and accurate using trend
analyses. Key words:proton therapy, daily QA, output, range, symmetry.
PMID- 28517303
TI - SU-E-T-233: Evaluation of Superficial Doses for Postmastectomy Radiotherapy.
AB - PURPOSE: To measure and to evaluate the surface and superficial doses for
patients requiring postmastectomy radiotherapy (PMRT) with different treatment
techniques. METHODS: An elliptic cylinder cork and super-flab boluses were used
to simulate the lung and the chest wall, respectively. Sets of CT images with
chest wall thicknesses of 5, 8, 10, 13, and 15 mm were acquired. Hypothetical
clinical target volumes were outlined and modified to fit a margin of 1 -3 mm
away from the surface. The planning target volume was initially created by
expanding an isotropic 3 mm margin from CTV and then a margin of 1-3 mm was
shrunk from the phantom surface. Treatment techniques using a pair of tangential
wedged fields (TWF) and 4-field IMRT were designed with a prescribed fraction
dose (Dp) of 180 cGy. Superficial dose profiles around the phantom circumference
at depths of 0, 1, 2, 3, and 5 mm were obtained for each treatment technique
using radiochromic external beam therapy (EBT) films. RESULTS: The TWF plans show
a dose buildup about 3 mm at the median and lateral tangential incident regions
with a surface dose of about 52% of Dp. Dose profiles were more uniform in the
PTV region for the 4-F IMRT plans. Most of the PTV region had doses higher than
94% of Dp at depths larger than 1 mm. The mean surface dose was about 65% of Dp
for the 4-F IMRT plans. The maximum dose for the 4-F IMRT plans was less than
118.4% of Dp. CONCLUSIONS: The dose variations caused by the oblique incidence
and a thin chest wall are modulated and reduced in the IMRT plans. More uniform
dose distributions within the PTV are obtained with the 4-F IMRT plans.
PMID- 28517304
TI - SU-E-T-226: Clinical Implementation of a Gravity-Oriented Wedge for Total Body
Irradiation.
AB - PURPOSE: To describe a TBI technique designed within the limits of a small-room
geometry and its clinical implementation. METHODS: Following construction of the
universal treatment devices, including the double-wedge, beam spoiler table, and
patient support table, commissioning consists of measurements to determine the
output, tissue-phantom ratio, effective source distance, and off-axis factor.
Dose is calculated by applying these factors per patient-specific measurements to
arbitrary point in the patient. Typically, ten calculation points are located at
mid-separation along the mid-sagittal plane from the head to the ankles. When
areas of unacceptably high dose are calculated, custom compensators are
constructed from 5-mm sheets of PMMA and placed over the patient on top of the
beam spoiler table. The typical dose homogeneity of the planning calculations is
within 2% of the prescribed dose. RESULTS: To verify the accuracy of the
technique, an anthropomorphic phantom was simulated and treated. In total, 128
thermoluminescent dosimeters (TLDs) were irradiated within the phantom.
Concentrations of TLDs were located in the planes of selected calculation points,
i.e. the head, neck, sternum, lung, umbilicus, and pelvis. Results showed the
average dose to these locations differed from the intended dose by -3.5%, 3.4%,
2.6%, 9.5%, 2.8%, and 0.5%, respectively. Due to its heterogeneous material, a
higher discrepancy in the lung dose was anticipated. To demonstrate the
dosimetric size of the radiation field, ionization chamber measurements were
taken on one lateral side of the treatment area at a constant depth of 5 cm. A
few measurements on the contralateral side were within 1 %, verifying the field's
lateral symmetry. The approximate treatment area for the current technique is
approximately 180*50 cm. CONCLUSIONS: We have demonstrated a small-room technique
capable of meeting the dosimetric goal of TBI. To improve the dosimetric
characteristics, new universal treatment devices are currently being designed and
constructed.
PMID- 28517305
TI - SU-E-T-254: Quantitative Evaluation of Three Mathematical Models for Radiation
Induced Secondary Cancer Risk for Lung in Stereotactic Body Radiotherapy.
AB - PURPOSE: Several mathematical models exist to predict secondary cancer risks from
radiotherapy treatment. In this study, we aimed to compare three dosimetry-based
models in the application of stereotactic body radiotherapy (SBRT) of early-stage
non-small cell lung cancer (NSCLC) with three radiotherapy treatment modalities.
METHODS: Ten patients who received definitive SBRT for early-stage NSCLC were
retrospectively selected. for each patient, a helical tomotherapy (HT) plan, a
three-dimensional conformal radiotherapy (3D-CRT) plan, and a volumetric
modulated arc therapy (VMAT) plan were generated to deliver 50 Gy to the planning
target volume in five fractions. The excess absolute risk (EAR) for secondary
lung cancer occurrence was calculated using three risk models: the linear
exponential model, the plateau model, and the linear model. The sensitivity of
the EAR to the prescription dose was evaluated by varying the prescription dose
in the range of 40 to 60 Gy. RESULTS: Based on the linear-exponential model, the
average EAR's (in occurrences per 10,000 patients per year) were 8.4+/-2.7, 8.3+/
2.1, and 8.4+/-1.9 for the HT plans, 3D-CRT plans, and VMAT plans respectively
with 40 Gy prescription dose, and 9.4+/-2.5, 9.0+/-2.1, and 9.3+/-1.8 with 60 Gy.
Based on the plateau model, the average EAR's were 10.7+/-3.9, 10.6+/-3.0, and
10.9+/-2.8 with 40 Gy, and 12.9+/-4.2, 12.6+/-3.4, 12.9+/-3.1 with 60 Gy. Based
on the linear model, the average EAR's were 29.1+/-13.4, 29.4+/-11.4, and 30.0+/
11.1 with 40 Gy, and 43.8+/-20.1, 44.0+/-11.0, 45.1+/-16.6 with 60 Gy. The
difference in EAR's were not statistically significant among the HT, 3D-CRT, and
VMAT plans. CONCLUSIONS: Three secondary cancer risk models, as well as three
SBRT treatment modalities, were compared. There was no significant difference in
secondary lung cancer risks among the three treatment modalities in this study.
PMID- 28517306
TI - SU-E-T-239: In Vivo Dosimetry with Surface Diodes during Total Body Irradiation:
A Patient Thickness Factor to Correct Midline Dose.
AB - PURPOSE: In vivo dosimetry (IVD) assessment of treatment dose is important when
delivering total body irradiation (TBI). One method is to average AP and PA
surface diode measurements and compare them to prescribed midline doses. We
designed phantom studies to examine the impact of patient thickness on surface
IVD measurements under TBI conditions. METHODS: Phantom studies were designed to
assess the effects of patient thickness on diode IVD. Sun Nuclear QED diodes with
inherent buildup were placed on anterior and posterior surfaces of a solid water
phantom. Phantom thickness was varied between 20 and 40 cm. A PTW farmer chamber
was inserted in the center of the phantom at 425 SSD to reflect prescribed
midline dose, and 50 cGy was delivered to midline with 18 MV photons. Averaged
entrance and exit diode doses were then compared to farmer chamber measurements
of phantom midline dose. RESULTS: A trend of increased deviation with increasing
umbilicus thickness was observed between averaged surface diodes and midline
farmer chamber measurements. Averaged surface diode dose ranged from 49.6 cGy (20
cm thickness) to 52.1 cGy (40 cm thickness). Interpolation of diode measurements
to midline resulted in linear overestimation of delivered dose relative to farmer
chamber measurements at midline, up to 6.8% at 40 cm umbilicus thickness.
CONCLUSION: Accurate in vivo dosimetry at time of patient TBI is important to
allow individual correction of MU exposure and tissue compensation. Without
patient thickness correction, overresponse of surface diodes may lead to
unnecessary clinical intervention to treatment MU or compensation and
insufficient midline dose. Additionally, SAD setup is preferable to SSD setup to
minimize thickness non-linearity. In conclusion, thickness correction factors
should be used to generate expected diode readings for patients with thickness
greater than 30 cm.
PMID- 28517307
TI - SU-E-T-248: An Extended Generalized Equivalent Uniform Dose Accounting for Dose
Range Dependency of Radio-Biological Parameters.
AB - PURPOSE: Introducing an extended, phenomenological, generalized equivalent
uniform dose (eEUD) that incorporates multiple volume-effect parameters for
different dose-ranges. METHODS: The generalized EUD (gEUD) was introduced as an
estimate of the EUD that incorporates a single, tissue-specific parameter - the
volume-effect-parameter (VEP) 'a'. As a purely phenomenological concept, its
radio-biological equivalency to a given inhomogeneous dose distribution is not a
priori clear and mechanistic models based on radio-biological parameters are
assumed to better resemble the underlying biology. However, for normal organs
mechanistic models are hard to derive, since the structural organization of the
tissue plays a significant role. Consequently, phenomenological approaches might
be especially useful in order to describe dose-response for normal tissues.
However, the single parameter used to estimate the gEUD may not suffice in
accurately representing more complex biological effects that have been discussed
in the literature. For instance, radio-biological parameters and hence the
effects of fractionation are known to be dose-range dependent. Therefore, we
propose an extended phenomenological eEUD formula that incorporates multiple VEPs
accounting for dose-range dependency. RESULTS: The eEUD introduced is a piecewise
polynomial expansion of the gEUD formula. In general, it allows for an arbitrary
number of VEPs, each valid for a certain dose-range. We proved that the formula
fulfills required mathematical and physical criteria such as invertibility of the
underlying dose-effect and continuity in dose. Furthermore, it contains the gEUD
as a special case, if all VEPs are equal to 'a' from the gEUD model. CONCLUSION:
The eEUD is a concept that expands the gEUD such that it can theoretically
represent dose-range dependent effects. Its practicality, however, remains to be
shown. As a next step, this will be done by estimating the eEUD from patient data
using maximum-likelihood based NTCP modelling in the same way it is commonly done
for the gEUD.
PMID- 28517308
TI - SU-E-T-218: The IHE-RO Helper Tool: Demonstrating the Connectivity Issues Solved
by IHE-RO.
AB - PURPOSE: To develop a Web-based application (IHE-RO Helper) to allow
comprehensive review of the interconnectivity and interoperability of various
radiotherapy devices established through testing sanctioned by the Integrating
Healthcare Enterprise-Radiation Oncology (IHE-RO). MATERIAL AND METHODS: IHE-RO
is an initiative sponsored by ASTRO to improve the way computer based systems in
radiation oncology share information using well-defined data exchange standards
(DICOM / HL7). At the IHE-RO Connectathon events over the last 4 years, 11
vendors with 14 different products have successfully tested and identified
solutions to connectivity problems in treatment planning, simulation and
delivery. Because the test results are highly technical, the interconnectivity
issues amongst the RT devices may get overlooked by the end users. The IHE-RO
helper tool is designed to operate in simple clinical terms with queries and
presentations organized based on treatment techniques and clinical features that
are familiar to the practitioners. For example, if you are planning to purchase a
treatment planning system capable of generating plans (e.g. Stereotactic
treatments) and are concerned whether the TPS can successfully transfer such data
to your treatment management system (TMS) and subsequently to your treatment
delivery system (TDS), the IHE-RO Helper can identify the connectivity
requirements and list vendors that have successfully passed an IHE-RO
Connectathon and validated their solution to the specific requirements. RESULTS:
The IHE-RO helper tool provides a graphical and textual user interface to
effectively demonstrate the solved interconnectivity problems between TPS, TMS
and TDS. A report is also provided that explains the interconnectivity problems
and its solutions. CONCLUSIONS: The IHE-RO helper is an effective tool to clearly
identify vendor products that are IHE-RO compliant, thereby encourages vendor
participation in testing and validation. Such a tool will be invaluable in
procurement of new equipment to ensure a priori interoperability with anticipated
RT devices deployed in the clinic. This research and development project is
supported by the Bankhead-Coley Cancer Research Program grant # RC1-09BW-09
26833.
PMID- 28517309
TI - SU-E-T-258: Assessment of Radiation Induced Second Cancer Risks in Proton Therapy
and IMRT for Organs inside the Main Radiation Field.
AB - PURPOSE: Radiation therapy can potentially cause a second malignancy. There is
clinical evidence that those occur typically within the beam path in the
medium/high dose region. The purpose of this study was to assess the risk for
developing a radiation induced tumor within the treated volume and to compare
this risk for proton therapy and IMRT. METHODS: Fully contoured age and gender
specific whole body phantoms (4-year and 14-year old) were uploaded into a
treatment planning system and typical tumor volumes were contoured based on
patients treated for optic glioma and vertebral body Ewing's sarcoma. Lifetime
attributable risks (LARs) for developing a second malignancy were calculated
using a risk model incorporating factors for cell kill, mutations, repopulation,
and inhomogeneous organ doses. RESULTS: For standard fractionation schemes, the
LAR for developing a second malignancy from radiation therapy alone were found to
be up to 2.7% for a 4-year old optic glioma patient treated with IMRT considering
a soft tissue carcinoma risk model only. Sarcoma risks were found to be below 1%
in all cases. For the 14-year old, risks were found to be about a factor of 2
lower. For the Ewing's sarcoma cases the risks based on the sarcoma model were
typically higher than the carcinoma risks, i.e. up to 1.3% LAR for soft tissue
sarcoma. Generally, the risk from proton therapy turned out to be lower by a
factor of 2 to 10. However, comparison of a 3-field and 4-field proton plan shows
that the distribution of the dose, i.e., the particular treatment plan, plays a
role as well. CONCLUSIONS: In general, proton therapy can significantly reduce
the risk for developing an in-field second malignancy. Risk analysis based on our
formalism could be applied within treatment planning programs to guide treatment
plans for pediatric patients. Federal Share of program income earned by
Massachusetts General Hospital on NIH/NCI C06 CA059267.
PMID- 28517310
TI - SU-E-T-228: The Beauty and the Beast: Transition from Film/paper Charts to
Paperless Environment with a New TrueBeam/ARIA System in a Small Community
Hospital on a Tight Budget.
AB - PURPOSE: To review the issues a physicist may encounter in a community hospital
during the transition from film/paper charts to a paperless environment with ARIA
and a TrueBeam LINAC. With a lean budget, it was necessary for the physics group
to take on the project management responsibilities in order save costs. This work
highlights the lessons learned during the planning and execution of our project.
METHODS: Like many hospitals around the county, our hospital was caught in the
economic downturn and was unable to provide all of the capital necessary to
upgrade to the radiation oncology department. However, with the support of the
hospital foundation, a total of $6M was secured for new LINAC, ARIA and CT
simulator. To save costs on facilities and computers, it was necessary for the
physics group to be involved in creating architectural drawings for shielding
calculations, finding a vendor to remove the old linac, assisting the foundation
to raise money, submission of the 'Certificate of Need' approval with the state,
negotiation with vendors, IT infrastructure, reviews with the general contractor
and vendor's project team, and ultimately writing the commissioning reports for
the new systems as well as developing new policies and procedures. RESULTS:
During a period of 4 months, the old LINAC was removed, facility renovations
made, the TrueBeam linac was installed, accepted, and commissioned and first
patients were treated. In addition, we transitioned from a film/paper environment
to a paperless environment. However, this was very stressful for staff and it may
be advisable to stage such a project over a longer period of time. There was also
significant lost revenue (~$2M) during downtime of construction, installation,
and commissioning. CONCLUSIONS: The radiation oncology department was upgraded
(The Beauty) on a tight budget but at the cost of added stress (The Beast) to the
staff.
PMID- 28517311
TI - SU-E-T-243: Dosimeter Parameters Comparison of TrueBeam, Trilogy, and IX
Machines.
AB - PURPOSE: Besides flattening-filter-free beams, Varian TureBeam Linac also has
conventional flattened photon beams. In our facility, we have TrueBeam, Trilogy
and iX machines from Varian; they all have same energy specifications: 6 and 10
MV photon beams, as well as 6, 9, 12, 16 and 20 MeV electron beams. This study is
to compare the photon and electron beams dosimeter parameters among the three
machines. METHODS: Beam data (including PDDs, inline and crossline profiles at
various field sizes and various depths) were collected using Sun Nuclear
Dosimetry 3D Scanner with nominal 100 cm SSD setup. These data were post
processed using Sun Nuclear Dosimetry software, including normalization,
interpolation and smoothing. The ion chambers used for scanning are IBA CC13.
RESULTS: Photon beams: The percentage depth doses with field sizes of 4*4, 6*6,
10*10, 15*15, 20*20, 30*30 and 40*40 cm * cm of 6 MV and 10 MV photon beams from
the three machines are very close. Compared with Varian Golden Beam Data, the
maximal variation of PDDs at depths of 5, 10, 15, 20, and 30 cm is 1.0%, with
mean value 0.6% and standard deviation 0.28% for 6 MV; for 10 MV beams, they are
2.0% (at depth of 30 cm), 0.9%, and 0.48% respectively. Also, the three machines
have very similar beam profiles; the profiles' shoulder, penumbra and umbra match
well for both inline and crossline beam profiles at various field sizes and
various depths.Electron beams: As compared the percentage surface doses (0.5 mm
from the surface), dmax, R90, R80, R50, and R30 of electron beams with energy of
6, 9, 12, 16, and 20 MeV at 10 cm cone, the electron beams of TrueBeam and iX are
almost identical. CONCLUSIONS: The 6 and 10 MV photon beam data of TrueBeam,
Trilogy, and iX have a same variation range when comparing with Varian Golden
Beam Data.
PMID- 28517312
TI - SU-E-T-212: Clinical Deployment of an Automatic Planning Interface for Overlap
Volume Histogram Based Treatment Planning.
AB - PURPOSE: To develop and deploy an interface to support automatic treatment
planning which predicts achievable dose levels for organs at risk (OARs) from
patients with similar or more complicated anatomies queried from a database. This
interface will provide an easy to use method of selecting the best known
achievable dose values for a given patient, and use them to automate the planning
process. METHODS: An overlap volume histogram (OVH) describes the distance a
target structure can be expanded with the volume of the compared overlap
structure. An OVH is generated for each target/critical structure pair and stored
in a database with dose-volume histograms (DVHs) for each patient. For all
patients, structures are consistently named by mapping ROI names to a set of
common names. For a new patient, the patient database is queried for the lowest
achievable dose for each OAR from patients in the database with the same or lower
overlap distance. The plan parameters and generated objectives are then
automatically loaded into treatment planning system for optimization. The final
clinical plan from each patient is added to the database to improve the results
of future queries. RESULTS: The system has been accepted by the dosimetrists for
clinical use. Automatically generated plans required less dosimetrist interaction
to achieve similar coverage to manually generated plans while OAR doses were
reduced or no worse than the manually generated plans. CONCLUSION: Automatic
planning tools can aid dosimetrists in quickly generating plans which maintain
target coverage and produce comparable or reduced dose to OARs. Our interface has
simplified the process enabling the broader use of the system across our
dosimetry staff. Philips stock ownership Philips Sponsored Research Elekta
Sponsored Research Elekta Patent License Accuray (Tomotherapy) Patent License.
PMID- 28517313
TI - SU-E-T-252: Consolidating Duodenal/Small Bowel Toxicity Data via Iso-Effective
Dose Calculations Based on Compiled Clinical Data.
AB - PURPOSE: To consolidate duodenal toxicity data from clinical studies with
different dose fractionation schemes using the modified linear quadratic (MLQ)
model. A methodology of adjusting the dose-volume parameters todifferent levels
of normal tissue complication probability (NTCP) was proposed and used to
estimate dose-volume constrains for treatment planning. METHODS: A set of
modified Lyman model parameters for duodenum NTCP were estimated by the chi
squared fitting method using tolerance dose and equivalent uniform dose (EUD)
data obtained in a literature search. These model parameters were then used to
convert the dose-volume pair, (D, V) to the iso-effective dose (in 2 Gy per
fraction)- volume pair, (DMLQED2, V). A relationship was derived to convert a
given DMLQED2 at one level of NTCP, to an iso-effective dose at another NTCP.
RESULTS: The literature search yielded six reports useful in making estimates of
small bowel/duodenal toxicity. The modified Lyman model parameters were found to
be TD50 = 60.9 +/- 7.9 Gy, m = 0.21 +/- 0.05, and I = 0.09 +/- 0.03 Gy-1. The
toxicity rates associated with hypo-fractionated radiotherapy (HBRT) were found
to be consistent with other clinical data of conventional fractionations found in
the literature. The conversion of DMLQED2 between different NTCP levels remains
consistent with each other over a narrow range of NTCP. CONCLUSION: MLQ based iso
effective calculations of dose-response data corresponding to Grade > 2 toxicity
were found to be consistent with one another within the uncertainty of DMLQED2
due to model parameter uncertainty. The dose-volume data that can be converted to
different NTCP levels may be used to estimate duodenal/small bowel dose-volume
constrains for new dose fractionation and/or dose escalation strategies. Medical
College of Wisconsin Cancer Center Meinerz Foundation.
PMID- 28517314
TI - SU-E-T-221: Evaluation of Technology Using Probabilistic Decision Models.
AB - PURPOSE: Medical physicists are often asked to evaluate or choose
appropriatetechnology for clinical applications. These are
multidimensionalproblems that also suffer from different degrees of uncertainty
in thevariables. Probabilistic decision models are a robust andmathematically
correct means of handling these issues. The principlesof constructing such models
are presented along with practicalexamples in the areas of IGRT, IMRT and proton
therapy. METHODS: Influence diagrams are used to model the variables and
theiruncertainties and include action and reward variables. Influencediagrams are
directed acyclic graphs that use Bayesian probabilitycalculus to propagate
probabilities and to update prior probabilitiesin the presence of evidence. An
influence diagram was used to modelthe question of whether brain tumors are
better treated with x-rayIMRT or proton therapy, with or without CT-guided
localization. Datafor the conditional probabilities of the model were obtained
from theliterature and included models of TCP, NTCP and induction of
secondmalignancies, as well as data on the probability density functions
forinterfraction patient motion. Dosimetric data were obtained using theCMS
treatment planning system. RESULTS: Several different tumor types and sites were
studied. The critical variables in the model were identified andstudied using
analyses of evidence, parameters and value ofinformation. The impact of imaging
was significant, regardless of theradiation type. The models used in determining
some of theconditional probabilities parameters also played an important role
inranking alternatives. CONCLUSIONS: Although such choices are difficult,
physicists mustproceed with the best data at hand. Without a rigorous framework
onwhich to build a model of the process, decisions are likely to be based
onunstated assumptions and incorrect inference. The example ofcomparing
irradiation modalities for brain tumors shows the power ofinfluence diagrams in
this critical context.
PMID- 28517315
TI - SU-E-T-262: Treatment Room Activation after 15 MV Single Fraction Radiation
Treatments Delivered Using Varian's TrueBeam and Trilogy Linear Accelerators.
AB - PURPOSE: To measure radiation levels in treatment room due to activation after
15MV single fraction radiation treatment (SFRT) delivered to a solid water
phantom. METHODS: We performed radiation surveys of two LINAC treatment rooms
immediately after 15 MV SFRT. We delivered a sequence of two 15 MV single
fraction IMRT treatments to a phantom at the end of a typical treatment day. The
first treatment delivered was 6201MU (about 12 Gy) and the second one, 15 minutes
later was 12711 MU (24 Gy). Both were delivered to the pelvic region of a solid
water anthropomorphic phantom. In a second technique, a 15 MV VMAT SFRT (4326 MU)
was delivered using the Varian TrueBeam LINAC. Radiation measurements were
recorded repetitively at four locations using a thin windowed Geiger Muller
detector, a sodium iodide photon spectrometer and a pressurized ionization
chamber. The four locations surveyed were: the top of the collimator head, the
collimator window surface, the isocenter, and the inferior end of the patient
support assembly. RESULTS: Radiation levels at the isocenter at the end of the
treatment day and before the two IMRT SFRTs varied from 0.06 to 0.1 mR/h. Within
2-3 minutes after finishing the second IMRT SFRT the radiation levels were
approximately 10 and 1.4 mR/h at isocenter for the TrueBeam and Trilogy rooms
respectively and around 0.6 mR/h for the TrueBeam VMAT SFRT. Closing the MLC and
the jaws significantly reduces the radiation level at isocenter. The average half
life of the mixture of radionuclides produced is about 10 minutes. CONCLUSIONS:
High dose single fraction IMRT treatments with 15 MV photons produce elevated
treatment room activation as compared to conventional IMRT. In addition,
activation levels varied between the TrueBeam and Trilogy for similar SFRT
schemes. There is no funding support, disclosures, or conflict of interest.
PMID- 28517316
TI - SU-E-T-232: Proton Source Modeling for Geant4 Monte Carlo Simulations.
AB - PURPOSE: To investigate the effect of initial proton beam source placement,
distribution and angle on the proton dose distribution in a therapeutic nozzle
using Geant4. METHODS: We performed Geant4 Monte Carlo simulations of a passively
scattered proton treatment nozzle. Accurate geometry including all elements in
the treatment room was used. Protons were generated just inside the vacuum pipe
using one of two models. First, a standard two dimensional Gaussian distribution
of proton starting position was used with a small random angle added to the
initial direction. The size of the Gaussian distribution and the random angle
were set to match measured beam spot size and angular spread at the exit window.
Second, a point source of protons further back in the vacuum pipe with a small
random angle was used. The distance of the point source to exit window and the
random angle were set to match the spot size and angular deviation used for the
Gaussian distribution. Depth dose curves and orthogonal beam profiles were
examined to determine changes between the two models. RESULTS: Orthogonal beam
profiles for large apertures showed changes of up to 6.5% between the two models
with the point source showing much better agreement with measured data. Depth
dose curves and orthogonal profiles for small apertures were unaffected. For
large apertures, the average difference compared to measured data was of 1.9% and
0.7% and the max difference was 5.0% and 1.6% for Gaussian and point sources,
respectively. CONCLUSIONS: The point source more realistically models the proton
distribution in the vacuum pipe by correlating the proton position with the
direction. For certain scattering setups and large apertures point source
modeling is necessary to accurate match measured data with Monte Carlo
simulations.
PMID- 28517317
TI - SU-E-T-206: Standardization in Documentation Format Can Significantly Reduce
Manual Data Entry Error in Patient Chart.
AB - PURPOSE: To demonstrate that standardization in documentation format can
significantly reduce manual data entry error in patient chart. METHOD AND
MATERIALS: Due to lack of direct data link between CT on rail imaging
registration software and patient R&V system, therapists have to manually enter
translation correction of patient position into R&V system after performing
imaging registration between CT image taken just before treatment delivery and
treatment planning CT image. Approximately six months after CT on rail was placed
into clinical service, we started requiring therapists to use a standard format
to document the shifts when they manually enter data to reduce manual data entry
error rate. The therapist manual data entry errors in R&V system before (551
entries) and after the format standardization (1645 entries) are the subjects of
statistical analysis. The errors are divided into two categories (recoverable and
non-recoverable errors) depending on whether a human being can recover the
translation shifts in lateral, longitudinal, and vertical directions from the
therapist notes. Fisher's exact test is performed to test the statistical
significance of therapist's data entry error reduction after our imposing the
documentation format requirement. Temporal information on when the errors were
made is also analyzed to find out when errors are more likely to happen. RESULTS:
Statistical analysis indicated that reductions in the numbers of recoverable, non
recoverable, and total errors after standardization in document format are all
statistically significant with p values less than 0.05. CONCLUSION: A simple and
low cost measure like standardization in document format can significantly reduce
the errors operators introduce to patient R&V system when they perform manual
data entry. We hope our experience will convince people to follow more
disciplined documentation rule to reduce the error rate and therefore potentially
can improve the quality of patient care when manual data entry is involved.
PMID- 28517318
TI - SU-E-T-216: TPS QC Supporting Program by a Third-Party Evaluation Agency in
Japan.
AB - PURPOSE: To equalize the quality of radiation therapy in Japan by supporting
quality control of radiation treatment planning system. METHODS: Center for
Cancer Control and Information Service in National Cancer Center supports the QA
QC of the cancer core hospitals in Japan as a third-party evaluation agency.
Recently, a program for assessing the quality of treatment planning system (TPS)
began as a part of our QA-QC supporting activities. In this program, a
questionnaire about TPS was sent to 45 prefectural cancer core hospitals in
Japan. The object of this questionnaire is to assess the proper commissioning,
implement and applications of TPSs. The contents of the questionnaire are as
follows; 1) calculate MUs which deliver 1000 cGy to the point of SSD = 100 cm, 10
cm depth with field sizes ranging from 5*5 to 30 * 30 cm2 , and obtain doses at
several depths for the calculated MUs, 2) calculate MUs which deliver 1000 cGy to
the point of SSD = 100 cm, 10 cm depth for wedge fields whose angles are from 15
to 60 degrees, and obtain doses at several depths with the MUs, 3) calculate MU
which deliver 1000 cGy to the point of STD = 100 cm, 10 cm depth with 10*10 cm2
field size and obtain doses at several depths with the MU. RESULTS: In this
program, 179 beam data from 44 facilities were collected. Data were compared in
terms of dose per MU, output factor, wedge factor and TMR. It was found that 90%
of the data agreed within 2%. CONCLUSIONS: The quality of the treatment planning
system was investigated through the questionnaire including the information of
essential beam data. We compared 179 beam data in TPSs sent from 44 facilities
and 90% of the data showed good agreement.
PMID- 28517319
TI - SU-E-T-225: A Comprehensive Evaluation of Real-Time Motion Tracking of a Surface
Imaging System for Lung Treatment.
AB - PURPOSE: Applicability of the AlignRT surface imaging system was extensively
investigated for real-time motion tracking in radiation therapy of lung cancer.
METHODS: A 4D computer-controlled motion phantom was employed to simulate a human
breathing motion. An anthropomorphic thoracic phantom (a coronal cross-sectional
area: ~1,200 cm2 ) was monitored during the 4D motion tracking. A breathing cycle
from a healthy subject (breathing frequency: 0.2 Hz; maximum amplitude: vertical
7 mm, longitudinal 6 mm, and lateral 1.2 mm) was monitored and fed into the
phantom control system. The real time monitoring was investigated by modifying a
region of detection (the whole, a half, and a quarter of the area) and
combination of 3 cameras (patient left, middle, and right). RESULTS: The real
time tracking errors (detected breathing motion - the input of the subject's
breathing) of the phantom motion using one camera (lateral, longitudinal,
vertical) were (0.02+/-0.14 mm, -0.23+/-0.48 mm, -0.10+/-0.48 mm) with
ipsilateral halves of the area (frame rate: 1.52 Hz), (0.06+/-0.10 mm, -0.30+/
0.30 mm, -0.03-0.35 mm) with ipsilateral quarters (frame rate: 1.95 Hz), and
(0.19+/-0.96 mm, 0.29+/-1.50 mm, -0.46+/-1.58 mm) with contralateral quarters
(frame rate: 3.04 Hz). The detection errors using 2-camera combinations (left
middle and right-middle) were (-0.06+/-0.06 mm, -0.43+/-0.21 mm, 0.00+/-0.22 mm)
for the ipsilateral quarters and (-0.62+/-0.18 mm, -1.20+/-0.37 mm, 0.03+/-0.30
mm) for the contralateral quarters, respectively. The 3-camera tracking using
halves of the area presented an error of (-0.04+/-0.12 mm, -0.69+/-0.35 mm,
0.08+/-0.38 mm) with a frame rate of 0.62 Hz. CONCLUSIONS: To guarantee a sub
millimeter accuracy of realtime motion tracking in the lung treatment,
combination of 2 cameras or less, a frame rate of greater than the Nyquist
frequency (in this study fN = 2B (breathing frequency) = 0.4 Hz), and a tracking
area of less than an ipsilateral half of thoracic area is highly recommended.
PMID- 28517320
TI - SU-E-T-236: Brachytherapy for Breast Cancer Patients with Implanted Pacemeker,
Using Multi Lumen Partial Breast Applicator.
AB - PURPOSE: Discuss optimised Accelerated Partial Breast Irradiation (APBI) using a
Strut-Adjused Volume Implant (SAVI) applicator for patients with implanted
pacemeker, without overdosing or relocating the pacemaker. METHODS: A right
breast cancer patient with an in situ pacemaker (Medtronic model ADDR01) on the
right side underwent breast conservative surgery and was referred for Partial
Breast Irradiation (PBI) using Ir-192 High Dose Rate Brachytherapy. Preliminary
estimation of the pacemaker dose from a pre-insertion CT study was about 8 % of
the prescribed dose which exceeded the generally accepted dose of 2Gy. The
challenge was to use a suitable applicator to treat the tumor bed and 1cm margin
without exceeding the 2Gy limit to the pacemaker and the leads. A seven catheter
SAVI device was selected and implanted in the right breast in an optimal
direction and a 3D treatment plan was generated following a post insertion CT
scan, using the Oncentra Brachy treatment planning system. Optimization tools
namely anatomy based Inverse Planning Simulated Annealing (IPSA), and graphical
optimization were utilized to load and optimize the dwell time in the catheters
and reduce the dose received by the pacemaker. Device interrogation was conducted
before and after the treatment. All operational parameters of the pacemaker were
found to be normal.No change in the baseline reference values were observed.
RESULTS: Using the SAVI device it was possible to limit the pacemaker/ leads dose
to less than 2 Gy. Target V100, V95 and V90 were 90.1%, 95.5% and 98.5%
respectively. V150 and V200 being 18.6cc and 10.6cc respectively.Calculated
average point doses on pacemaker assembly for ten fractions was 140cGy.
CONCLUSIONS: By combining the optimization tools of today's Brachytherapy
planning system and a multilumen SAVI applicator, HDR partial breast irradiation
can be safely delivered for breast cancer patients with in situ pacemaker, with
out the fear of interrupting pacemaker functionality.
PMID- 28517321
TI - SU-E-T-253: Assessing Small-Volume Cord Biological Effective Dose for Repeat
Spinal Stereotactic Body Radiotherapy Treatments.
AB - PURPOSE: Small-volume biologically effective (BED) dose limits are critical to
safe spinal stereotactic body radiotherapy (SBRT) delivery. However, due to
mismatch in spatial location of dose hot spots from non-uniform dose
distributions inherent to SBRT, for repeat treatment courses they cannot be
simply added by assuming a uniform dose distribution. This study aims to develop
a probability-based biological equivalent dose formula to solve this problem.
METHODS: A generalized biological equivalent dose (gBED) was formulated via
computing damaging or survival probability of repeat spine SBRT treatments.
Parameters from the linear-quadratic model such as alpha/beta =2 Gy for the
spinal cord were applied for the gBED calculations. The derived method was
applied to both simulated and clinical treatment cases to demonstrate its
applicability and usefulness for assessing spinal cord dose limits for repeated
SBRT treatment courses. RESULTS: The gBED formula allows direct superposition of
dose within a small volume of spinal cord from a non-uniform dose distribution of
varying dose fractionation schemes of SBRT. From the studied examples,
traditional BED calculations even with full voxel-by-voxel tracking calculations
resulted in inconsistent BED values and can underestimate the biological dose to
a small-volume spinal cord by as much as 20%. Such an error tends to increase
rapidly with increasing volume of interests such as from 0.1 mL to 2.0 mL.
CONCLUSIONS: When assessing spinal cord tolerance for repeat spinal SBRT
treatments, consistent surrogates such as gBED are needed to avoid potential
underestimation of treatment-induced complications.
PMID- 28517322
TI - SU-E-T-238: Annual QA of Proton Gantry with Robotic Table.
AB - PURPOSE: To perform the annual QA of proton gantry with a robotic table. METHODS:
A new proton gantry with robotic table has been commissioned and is being used in
clinic for patient treatment. The gantry is equipped with a robotic table with 6
degrees of freedom and dual cardinal angle KV imagers for patient registration.
The system allows direct movement from one beam location to another without
additional image registration, which effectively reduces portal setup time and
increases treatment efficiency. The annual QA has four main components: Beam
parameter checks included proton depth dose, output, linearity, modulation
factor, field size factor, effective source distance, compensator gap factor, and
monitor unit comparison between model calibration and physical measurements for
every energy. Mechanical checks included gantry and robotic table isocenter,
gantry and robotic couch isocentricity, and mechanical movement of fully loaded
couch and corresponding digital readout. Imaging system checks included proton, X
ray beam, laser and image receptor alignment, image quality of KV imagers, and
image registration accuracy. The last were the system safety checks. Methods used
to perform these checks, especially those pertaining to robotic positioner will
be discussed. RESULTS: The new proton gantry and robotic table had the isocentric
accuracy of about 1 mm. The accuracy of mechanical movements of the robotic table
was within 1mm/0.5 degree in the clinical motion range. The accuracy of proton
outputs determined by IAEA TRS 398 protocol was within +/-2% and the consistency
of beam range for all clinical energies at cardinal gantry angles was within 1mm.
CONCLUSIONS: The results of the gantry annual QA demonstrate that the machine
satisfies the highest standards of quality assurance for proton radiation
treatment. The annual QA verifies the proton output, robotic table movement
accuracy, image registration and safety of the machine and thus increases our
confidence level in the uncertainties of daily proton treatments.
PMID- 28517323
TI - SU-E-T-247: Dose-Volummetrics in the Prediction of Pulmonary Function Changes
after Radiotherapy in Patients with Non-Small Cell Lung Cancer.
AB - PURPOSE: This aim was to explore the relationship between dose-volummetrics and
changes of pulmonary function tests (PFTs) and provide criteria of dose
volummetrics to predict these changes of PFTs after radiotherapy with NSCLC.
METHODS: Between March 2008 to November 2009,39 patients (male 30,female 9,
median age 66 years) with inoperable NSCLC received definitive 3DCRT or IMRT
treatment were included in this study. The GTV included primary tumor and
metastasis lymph node in hilar or mediastinum, and delineated the PTV from GTV
1.5 to 2.0 centimeter outside. The prescription doses ranged from 60-68Gy with a
median dose of 66Gy. The forced vital capacity(FVC), forced expiratory volume in
one second (FEV1.0) and diffusion capacity of carbon monoxide(DLCO) were checked
for each patient two times, one week pretreatment and 2 to 4 months after
radiotherapy. dose-volummetrics of lungV10,V15,V20,V25,V30,V35,V40, lung mean
dose and GTV100,GTV95, GTV90,GTV80 were analyzed. Statistical methods of Pearson
and Line regression were used to determine whether correlation existed between
these metrics and the changes in PFTs. RESULTS: This investigation showed that
FVC went down 2.4+/-1.6 from 77.2+/-18.7 to 74.1+/-18.5, FEV1.0 went down 5.9+/
3.2 from 74.1+/-20.5 to 70.9+/-20.2 P=0.065and DLCO went down 17.9+/-6.3 from
70.4+/-20.5 to 59.8+/-16.0 P=0.000 after radiotherapy. No correlation was found
between dose-volummterics and the changes in PFTs. Excluding patients(n=15)with
pretreatment atelectasis, significant correlation was retained between dose
volummetrics (lungV20,V25,V30,V35,V40, Lung mean dose and Veff) and the PFTs
changes (P=0.05).Multivariate analysis showed that lung V30 was risk factor for
the changes of FEV1.0 and DLCO(P=0.046 and 0.041).Furthermore analysis by
stratifies, compared lung V30=18% and <18%, the dropped values of FVC, FEV1.0,
DLCO were 6.9+/-2.5 and 4.5+/-1.8 P=0.061, 15.2+/-4.0 and 6.1+/-2.3 P=0.033,
22.8+/-2.0 and 11.6+/-1.4 P=0.000 respectively, showed PFTs became more worse
with lungV30=18%. CONCLUSIONS: lungV30 is risk factor to affect PFTs changes in
patients with NSCLC excluding those who have had pretreatment atelectasis. Our
funding support received from National Natural Science Foundation of China
(30870743).
PMID- 28517324
TI - SU-E-T-257: Risk of Radiogenic Second Cancer after Photon and Proton Craniospinal
Irradiation.
AB - PURPOSE: To compare proton and photon therapies in terms of the risks of second
cancers for a pediatric medulloblastoma patient receiving craniospinal
irradiation (CSI). METHODS: Two CSI treatment plans with 23.4 Gy or Gy (RBE)
prescribed dose were computed for a 4-year-old boy withmedulloblastoma: a three
field 6-MV photon therapy plan and a four-field proton therapy plan. The primary
doses for both plans were determined using a commercial treatment planning
system. Stray radiation doses for proton therapy were determined from Monte Carlo
simulations, and stray radiation doses for photon therapy were determined from
measured data. The dose-risk model based on Biological Effects of Ionization
Radiation VII report was used to estimate risk of second cancer. RESULTS:
Baseline predictions of the relative risk of each organ were always less for
proton CSI than for photon CSI after various follow-up years for the patient. The
lifetime risks of the incidence of second cancer after proton CSI and photon CSI
were 7.7% and 92%, respectively, and the ratio of lifetime risk was 0.083.
Uncertainty analysis revealed the qualitative findings of this study were
insensitive to any plausible changes of dose-risk models and mean neutron
radiation weighting factor. CONCLUSIONS: Proton therapy confers lower predicted
risk of second cancer for the pediatric medulloblastoma patient compared with
photon therapy.
PMID- 28517325
TI - SU-E-T-227: Re-Evaluation of Dose Distribution and Margins for IMRT Prostate
Plans.
AB - PURPOSE: To evaluate the dose distribution on prostate and proximal seminal
vesicles (SVs), rectum, and bladder when a certain geometry uncertainty is
occurred during planning or delivery, and further determine the optimistic margin
relation to different directions. METHODS: Thirty prostate cancer patients with
prostate specific antigen (PSA) less than 10 and Gleason Score between 2 and 6
have been selected and planned in EclipseTM 10.0 treatment planning system. PTV
is expanded from GTV (prostate plus proximal SVs) with uniform 6 mm margin in all
directions. All patients are head-first-supine and planned with seven beam IMRT
technique. At least 95% of PTV is covered by full prescription. Rectum V65 is
less than 17%, rectum V40 is less than 35%, bladder V65 is less than 25%, and
bladder V40 is less than 50%. To simulate the deviation from planning error or
setup uncertainty, the original isocenter of each plan has been shifted every 2mm
from 0mm to 10mm in superior (S), inferior (I), right (R), left (L), anterior
(A), and posterior (P) directions. The dose is then re-calculated with fixed jaw
technique. The new plan parameters such as PTV coverage, both bladder and rectum
V65 and V40 are analyzed. RESULTS: PTV full dose coverage is linearly decreasing
with increasing isocenter shift and the absolute slope mean values are 2.2, 2.2,
3.0, 2.7, 2.0, and 2.0 corresponding to S-I-P-A-L-R directions. As for rectum and
bladder, the further away from the shifted isocenter, the smaller values of V65
and V40. CONCLUSIONS: This study shows that 2 to 3 percentage of decrements on
PTV full dose coverage occurs while prostate target shifts every millimeter. To
uniformly cover the dosimetric impact uncertainty, it shows that the optimistic
margin ratio would be 1.1(S):1.1(I):1.5(P):1.35(A):1(L):1(R) for the six
directions.
PMID- 28517326
TI - SU-E-T-242: Effect of Skull Surgical Clips and Bone Artifacts on Treatment
Planning for Brain Tumors with Proton Beam.
AB - PURPOSE: To study the effect of skull surgical clips and bone artifacts on dose
distribution using proton beams for treatment planning. METHODS: Proton treatment
plans with double scattering technique for ten patients were generated on
patients with brain tumors having had prior surgery with skull bone surgical
clips. Appropriate clinical, dosimetric and geometric margins were added for each
tumor volume and dose was prescribed to clinical target volume (CTV). The CT
images used for treatment planning show streaking artifacts due to the clips and
there are also soft artifacts on tissue adjacent to skull bone due to high
density of bone. We performed two plans for each patient; a plan without
correcting for artifacts and a second plan replacing the artifacts with normal
tissue. For the second plan, the artifacts were contoured and a CT numbers
obtained by sampling pixels in adjacent areas without artifacts was assigned to
the contours. We compared the two plans by evaluating the dose volume histogram
(DVH) for tumor coverage and the mean, median, and maximum dose for normal tissue
structures. RESULTS: Volume of CTV receiving 99% of the prescribed dose (PD) show
a mean difference of 3% higher dose for artifact corrected plans. The normal
tissue structures comparison shows and average dose difference of 5%, 8%, 11%,
and 30% lower doses for optical chiasm, temporal lobes, brain and optic nerves
for artifact corrected plans respectively. CONCLUSIONS: In general when using
artifact correction for surgical skull clips and skull bone, the tumor coverage
tends to be slightly higher. Overall, the normal tissue structures tend to have
lower doses depending on the volume, position and the geometry for artifact
corrected plans. We recommend the correction of artifacts due to surgical clips
and skull bone for brain region proton planning.
PMID- 28517327
TI - SU-E-T-211: Peer Review System for Ensuring Quality of Radiation Therapy
Treatments.
AB - PURPOSE: To demonstrate a Web-based electronic peer review system that has the
potential to improve quality of care for radiation therapy patients. The system
provides tools that allow radiation oncologists to seek peer review of target and
critical structure delineation, treatment plans, and share clinical data with
peers to optimize radiation therapy treatments. MATERIAL AND METHODS: Peer review
of radiation therapy treatment planning data prior to its initiation improves the
quality of radiation therapy and clinical outcomes. Web-based access to radiation
therapy treatment planning data and medical records mitigate existing
geographical and temporal constraints. With internet access, the healthcare
provider can access the data from any location and review it in an interactive
and collaborative manner. Interoperability standard like DICOM-RT and IHE-RO
compliant RT Systems have facilitated the design and implementation of PRS with
Silverlight Web technology, .net Framework and SQL Server. Local DICOM-RT archive
and cloud based services are deployed to facilitate remote peer reviews. RESULTS:
To validate the PRS system, we tested the system for 100 patients with Philips
Pinnacle v 9.0 and Varian Eclipse v 8.9 treatment planning system (TPS). We
transmitted the DICOM RT data from the TPS to the cloud based services via the
PRS local DICOM RT Archive. Various CT simulation based parameters such as
orientation of CT, properties of RT structures etc. were compared between the TPS
and PRS system. Data integrity of other parameters such as patient demographics
(patient name, ID, attending physician etc.) and dose volume related parameters
were also evaluated. Such rigorous testing allowed us to optimize the
functionalities and clinical implementation of the PRS. CONCLUSIONS: We believe
that the PRS will improve the quality and safety of a broad spectrum of radiation
therapy patients treated in underserved areas while discouraging the
overutilization of expensive radiation treatment modalities. This research and
development project is supported by the James and Ester King Biomedical Research
Program grant # RC1-09KW-09-26829.
PMID- 28517328
TI - SU-E-T-251: Analysis of Irradiated Induced Lung Injury in Non-Small Cell Lung
Cancer (NSCLC) Treated by Three-Dimensional Conformal Radiotherapy(3DCRT).
AB - PURPOSE: The aim of this study was to analyze the affect factors with radiation
induced lung injury of NSCLC treated by 3DCRT, in order to supply reference
criteria for optimize the treatment planning, further to improve the local
control rate and the quality of life of NSCLC patients. METHODS: From August 2000
to December 2004, 107 NSCLC patients received 3DCRT were retrospectively enrolled
in this study. All of patients received the prescription doses ranged from 60
68Gy with a median dose of 66Gy. Dosimetric parameters of dose-volume histograms
from 3DCRT plans was recorded. The lung injury were assessed for each patient
during the treatment and follow-up within 3 months after treatment completion.
Acute radiation induced pneumonitis were graded by one radiation oncologist
according to the RTOG/EORTC criteria. The correlation between dosimetric
parameters with lung injury was evaluated by univariate and multivariate analysis
using Logistic Regression Model of SPSS11.0 software. RESULTS: In the 107
patients of NSCLC, the rate of irradiated induced lung injury was 62.6% and the
rate of =2 grade radiation induced pneumonitis was 38.3%. Twenty-three cases were
classified in grade 2, fourteen cases in grade 3, four cases in grade 4.
Univariate analysis showed chronic obstructive pulmonary disease(COPD), number of
beams field, lung mean dose, lung V5-V40 were important parameters on radiation
induced lung injury. The rate of =2 grade lung injury was 56.3%(18/32) in
patients accompany COPD, compared with 30.7%(23/75) of those without COPD. In the
same way,the rate of =2 grade lung injury was 61.9%(26/42) in patients of lung
mean dose=20Gy, which higher than 19.4%(12/62) of lung mean dose<20Gy. Further
more, lung mean dose, lung V20 and COPD were likely to be the independent factors
of radiation induced lung injury by Logistic Regression Model. CONCLUSIONS: lung
mean dose, lung V20 and COPD were the independent affect factors on irradiated
induced lung injury. Our funding support received from National Natural Science
Foundation of China (30870743).
PMID- 28517329
TI - SU-E-T-261: Determination of Initial Exposure Rates and Clearance Constants in a
Sequence of 165 Consecutive Thyroid Cancer Patients Undergoing NaI-131 Therapy.
AB - PURPOSE: Following surgery, papillary and follicular thyroid cancers are usually
treated with oral administration of NaI-131. In order to estimate subsequent
staff, family, and public exposures, it is important to measure both exposure
rates as well as the time of clearance of residual activity from these
individuals. There is the additional possibility that patient whole-body absorbed
dose estimates may be made using the data. METHODS: During the historical
interval 2006 - 2010, a total of 165 consecutive thyroid cancer patients were
assayed at the time of activity administration and over the following several
days. Using a calibrated radiation detector, exposure rates at one meter from the
navel were measured between 2 and 5 times before release. By using these
measurements and assuming a single-exponential clearance, we were able to
evaluate initial exposure rates as well as the biological rate constant [k(biol)]
for clearance of I-131 from the body. RESULTS: Regression analyses were used to
fit the initial exposure [X(0)] results as a function of administered activity.
By least-squares, the slope was determined to be 0.15 mR/h/mCi over a clinically
determined activity range of 25 to 250 mCi. At a given activity, there was wide
variation of X(0) due to individual factors such as amount of residual thyroid
mass and body habitus. For example, at 150 mCi, X(0) varied from 15 to 35 mR/h at
one meter with the average being 25 mR/h. For the 165 patients, the mean
biological clearance constant was 0.049/h. CONCLUSION: Average initial exposure
rates at one meter from 165 NaI-131 patients have been determined. The biological
clearance was seen to be much more rapid than the physical decay constant for I
131 (0.0036/h). At a given activity level, variation of exposure rates was
approximately +/- 40% over the corresponding patient population.
PMID- 28517330
TI - SU-E-T-231: Comparison of Beam Characteristics of Small Field 6 MeV Electrons as
Replacement for Superficial X Ray Beam.
AB - PURPOSE: To compare beam characteristics of superficial X-rays with 6 MeV
Electrons for the purpose of replacing superficial treatments with electron
fields for skin lesions. METHODS: Electron beam cutouts were made with 12mm
thickness cerrobend in diameters 2-5 cm to match superficial X-ray machine cones.
Central axis depth doses and profiles were generated using 0.007 cc Exradin A-16
ion chamber, in PTW water phantom at 1mm steps, at 96 and 100cm SSD for electron
beams, and at 15cm SSD for superficial X-rays. From the beam data, radiation
penumbra 90-10%, 90% profile width, peripheral dose and percentage depth dose
were obtained for comparison. RESULTS: The 90-10% radiation penumbra was ranging
7.4-13.7 mm, 12.6-17.6 mm for 6 MeV electrons at 96 and 100cm SSD respectively,
and 4.2-11.4 mm for 2-5 cm superficial X-ray cones. For 90% treatment width, a
margin ranging 5-7 mm, 6-9 mm is needed around the periphery of target for 6 MeV
Electrons at 96 and 100cm SSD respectively, and 2-3 mm for superficial X-ray
cones. For 96cm SSD, the peripheral dose from the geometrical field edge were
3.9% at 1cm and 0.5% at 2cm. It was 2.6% at 1cm and 0.7% at 2cm for 100cm SSD.
For superficial, it was 6.2%, 7.5%, 9.1% at 1cm, and 3.4%, 4.3%, 5.6% at 2cm for
100 kV, 120 kV and 150 kV respectively. The electron surface dose was below 90%.
CONCLUSION: 6 MeV Electron beam shows high superiority with rapid fall off of
dose beyond target with lower peripheral dose compared to superficial X-rays.
However, the electrons need higher margin around the target and also need
appropriate bolus thickness to increase skin dose. The dose at depth beyond 2cm
makes very significant advantage using electrons compared to superficial X-rays.
PMID- 28517331
TI - SU-E-T-205: MLC Predictive Maintenance Using Statistical Process Control
Analysis.
AB - PURPOSE: MLC failure increases accelerator downtime and negatively affects the
clinic treatment delivery schedule. This study investigates the use of
Statistical Process Control (SPC), a modern quality control methodology, to
retrospectively evaluate MLC performance data thereby predicting the impending
failure of individual MLC leaves. METHODS: SPC, a methodology which detects
exceptional variability in a process, was used to analyze MLC leaf velocity data.
A MLC velocity test is performed weekly on all leaves during morning QA. The
leaves sweep 15 cm across the radiation field with the gantry pointing down. The
leaf speed is analyzed from the generated dynalog file using quality assurance
software. MLC leaf speeds in which a known motor failure occurred (8) and those
in which no motor replacement was performed (11) were retrospectively evaluated
for a 71 week period. SPC individual and moving range (I/MR) charts were used in
the analysis. The I/MR chart limits were calculated using the first twenty weeks
of data and set at 3 standard deviations from the mean. RESULTS: The MLCs in
which a motor failure occurred followed two general trends: (a) no data
indicating a change in leaf speed prior to failure (5 of 8) and (b) a series of
data points exceeding the limit prior to motor failure (3 of 8). I/MR charts for
a high percentage (8 of 11) of the non-replaced MLC motors indicated that only a
single point exceeded the limit. These single point excesses were deemed false
positives. CONCLUSIONS: SPC analysis using MLC performance data may be helpful in
detecting a significant percentage of impending failures of MLC motors. The
ability to detect MLC failure may depend on the method of failure (i.e. gradual
or catastrophic). Further study is needed to determine if increasing the sampling
frequency could increase reliability. Project was support by a grant from Varian
Medical Systems, Inc.
PMID- 28517332
TI - SU-E-T-215: A Technique for Treating Patients outside the Mosaiq R&V System for
TrueBeam Users (or 4DTC).
AB - PURPOSE: When the record and verify (R&V) system (Mosaiq, Elekta Medical Systems)
is unavailable to send information to the treatment console of the linear
accelerator (Varian Clinac, Varian Medical Systems), treatment is manually
delivered by entering parameters into the treatment console and loading backed up
MLC files. The new linear accelerator, the TrueBeam (Varian Medical Systems)
lacks the ability to manually deliver treatment by entering machine parameters
into the treatment console. METHODS: The TrueBeam can only deliver treatments
using the R&V system or loading DICOM RT plan files directly in File Mode. Every
time a prescription site is sent from the R&V system to the accelerator, a DICOM
RT plan file is created by the R&V system. A script was created that reads the
headers of these files, copies them to the treatment console and renames them in
an identifiable form. At the end of each treatment day, the script is executed
transferring only the DICOM RT plan files created that treatment day. A
contingency report is then generated from the R&V system, which contains machine
parameters for all fields for all patients under treatment. When the R&V system
is unavailable the RT plan files are opened in file mode, and the machine
parameters are verified using the contingency report before delivery. This system
was tested on a cohort of patients. Each patient's plan was opened in file mode
and the machine parameters were verified against the patient's planned treatment
in the R&V system. RESULTS: All files opened in file mode were identical to the
information stored in the R&V system. This was tested both on the TrueBeam and
accelerators having the 4DTC. CONCLUSIONS: Our technique was validated and is an
alternative method for delivering treatment when the R&V system is unavailable.
PMID- 28517333
TI - SU-E-T-224: Dose Distribution of Oesophagus Stents Measured by EBT2 Film
Dosimetry.
AB - PURPOSE: The purpose of this study is to investigate the dose enhancement at
oesophagus stents made of nitinol. The material is a nickel titan alloy with an
effective atomic number of 26. Because of the increased atomic number in
comparison to the human body, dose enhancement in surrounding tissue is expected.
METHODS: The relative dose distribution around the stent was measured in a water
phantom. To simulate the air cavity within the oesophagus, a styrodur cylinder
was placed inside the stent. The stent was held with a circular PMMA holder. An
EBT2 film was wrapped around the stent to measure the relative radial dose
distribution.The setup was irradiated with a 6MV photon beam (Siemens Primus) and
a field size of 5cmx5cm. The distance between source and centre of the stent was
100cm.The EBT2 films were digitized at a scanning resolution of 72dpi using an
Epson 10000XL flatbed scanner with a transparency unit. Furthermore, the films
were fixed in a frame to prevent Newton rings in the scanned image. RESULTS: The
dose increases in all directions around the stent. With approximately 18%, the
highest increase is caused on the proximal side of the stent. On the backside the
dose enhancement is approximately 10%. CONCLUSIONS: Dose enhancements around a
stent are detectable and one should be aware of it's occurence in the
radiotherapeutical treatment of oesophageal cancer. Because of the enhancement in
all directions healthy tissue may be affected.
PMID- 28517334
TI - SU-E-T-235: Dosimetry Study within a Millimeter from Beam Exiting Air-Tissue
Interface Using Film and Monte-Carlo Simulation on a Co-60 Beam.
AB - PURPOSE: Objective is to assess dose accuracy and uniformity to cells in a well
plate irradiated on Co-60 beam using film (EBT2) and Monte-Carlo simulation.
METHODS: Situations are encountered where dosimetry near beam-exiting air
interface is needed. Typical example is irradiation of cells in well-plate. Small
amount of cell emulsion may amount to as small as 1 mm thickness which results in
leaving large air space above the cells. Due to contamination concerns, air space
above cells can not be avoided. Preferred geometry for irradiation is to place
cell-plate on a build-up slab (water-equivalent), and point the beam upward. On
Co-60 beam, film EBT2 was employed to measure doses 0.1, 0.4, 0.7, 1.2 mm
upstream from air- interface. Film optical-density (OD) was measured with a
pocket densitometer, and converted to dose using film-calibration specific to
film-batch. To validate film data, Monte-Carlo code DOSXYZNRC was employed for
simulation. Doses were calculated employing (i) calculation grid 0.1-1.0 mm along
beam direction, and (ii) 15000 million incident particles to achieve < 0.2%
precision. RESULTS: Doses measured with film close to beam-exiting air-interface
are ~16% lower than the maximum doses 1.2 mm up-stream and beyond. Monte-Carlo
calculations validate the doses measured with film within measurement uncertainty
(2%). Dose variation is steep in the first 0.1 mm zone near air-interface, but it
is within 10% further up-stream. CONCLUSIONS: In cell irradiations, dose in
homogeneity in the top 1mm zone is significant. Layer close to air-interface
receives ~16% lower dose than the layer 1.2mm up-stream. Dose homogeneity with
the stated geometry can be improved by having (i) larger amount of cells to
provide emulsion thickness > 3mm, and (ii) non-homogeneous emulsion for cells to
settle at the bottom. Since dose in-homogeneity is primarily due to air
interface, results are expected to be qualitatively similar for other beams (Cs
137 or 6 MV.
PMID- 28517335
TI - SU-E-T-208: The Secondary Malignancy Risk Estimation Due to the Neutron
Contamination in 3D-CRT and IMRT Treatment Techniques by Using Bubble Detectors.
AB - PURPOSE: In this study, the neutron measurements were performed in free in air
and RW3 solid water phantom to estimate the secondary malignancy risk for three
dimensional conformal radiotherapy (3D-CRT) and intensity modulated radiotherapy
(IMRT) techniques in prostate cancer treatment. METHODS: Neutron dose were
measured in 18 MV Elekta Synergy Platform and Varian Clinac linear accelerators
by using bubble detector for personal neutron dosimetry (BD-PND). To determine
the neutron equivalent dose in different depths and different distance from the
edge of treatment field RW3 solid water phantom was used and organs location was
defined in Alderson Rando phantom with respect to target (prostate) position in
the treatment field. By using these data, we determined the neutron equivalent
dose and effective dose for the standard prostate cancer patient treated with 3D
CRT and IMRT with 18 MV photon energy. The total dose was 70 Gy in 3D-CRT and 76
Gy in IMRT treatment in the current study. For both of these treatment
techniques, we estimated the risk of secondary malignancies due to the neutron
contamination by using the International Commission on Radiological Protection
(ICRP) report 103. RESULTS: The equivalent dose and effective dose due the
neutron contamination were considerably high in 18 MV IMRT technique. The
secondary malignancy risk estimation for 3D-CRT and IMRT were found to be 0.44%
and 1.15% for Elekta Synergy Platform linear accelerator, 0.92% and 2.38% for the
Varian Clinac DHX High Performance linear accelerator, respectively. CONCLUSIONS:
Therefore, one should take care of the secondary malignancy risk in case of using
18 MV in IMRT applications.
PMID- 28517336
TI - SU-E-T-263: Luminescent Dosimetry to Measure the Out-Of-Field Low and High LET
Dose Components in High Energy Photon and Proton Therapy Beams.
AB - PURPOSE: Luminescent dosimetry using thermoluminescent detectors (TLDs) and
optically stimulated luminescent detectors (OSLDs) were used in mixed radiation
fields containing both low LET (photons and protons) and high LET
(neutrons)components to obtain their out-of-field absorbed dose, dose equivalent
and quality factor. METHOD AND MATERIALS: LiF Thermoluminescent Detectors (TLDs)
600 and 700 chips with dimensions 0.31*0.31*0.038 cm3 were used in a 25.4 cm
diameter Bonner sphere centered 42 cm from the isocenter of a 15*x15 cm2 field to
measure the secondary doses for 10, 15 and 18 MV photons and a 200 MeV proton
therapy beam. From the sensitivity difference to LET radiation between the210 and
280 C peaks in the glow curve, the areas under the peaks were used to obtain the
absorbed dose, dose equivalent and QF of the secondary radiation. The OSLD
detector measured the low LET dose component to compare with the TLD dose
measurement. The neutron calibration of the TLDs was obtained from an Am-Be
source at the Argonne National Laboratory. The photon and proton TLD and OSLD
calibrations were obtained in 6 MV and 200 MeV beams, respectively. RESULTS: From
the two-peak analysis of the TLDs in the Bonner sphere the ratios of the neutron
dose to photon dose were 0.001, 0.014 and 0.17 for 10, 15 and 18 MV,
respectively. The low LET OSLD measurements agreed within 10% of the TLD results.
From the dose equivalent measurements the QFs (+/-14%) obtained were 4.5, 3.9 and
4.0 for these beam energies. For the 200 MeV proton beam the ratio of neutron to
proton dose was 0.28 with a measured QF of 13. CONCLUSION: Luminescent detectors
in a Bonner Sphere provide measurements of the secondary photon, proton and
neutron doses and provide an estimate of the neutron QF.
PMID- 28517337
TI - SU-E-T-237: Leading 25 in 25: A Bibliometric Analysis of Classics Articles in
IMRT.
AB - PURPOSE: Scientific publication in IMRT has experienced significant development
since its introduction. Bibliometric analyses allow an understanding of how this
publication trend is organized at an aggregated level. Citation analysis is one
of the most widely used bibliometric tools of scientometrics. Analysis of
classics, defined as an articles with 100 or more citations, is common in the
biomedical sciences as it reflects an article's influence and the recognition it
receives in its professional and scientific community. Our objective was to
identify the 25 most frequently cited classic articles in IMRT in the past 25
years. METHODS: The 25 most-cited IMRT articles were identified by searching
ISI's Web of Knowledge and Pubmed databases for all related publications from
1986 through 2011. Articles were evaluated for several characteristics such as
author(s), institution, country of origin, publication year, type, and number of
citations. An unadjusted categorical analysis was performed to compare all
articles published in the search period. RESULTS: Our search yielded a cumulative
total of 37,197 entries for the publication period. Original research and
clinical trial articles accounted for 25,827 and 312, respectively, for a total
of 25,719 entries. The 25 most-cited articles were identified from the latter sum
and selected out of 123 classics. The number of citations per article ranged from
203 to 504. IMRT classics appeared in one general and five core journals.
CONCLUSIONS: This study analyzed publication patterns focused on IMRT, its most
influential classic articles, journals that published them, their authors and
other salient characteristics. Such information is of importance to researchers
and those who wish to study the history and development of the field.
PMID- 28517338
TI - SU-E-T-256: Radiation Dose Responses for Chemoradiation Therapy of Pancreatic
Cancer: An Analysis of Compiled Clinical Data Using Biophysical Models.
AB - PURPOSE: We have analyzed recent clinical data obtained from chemoradiation of
unresectable, locally advanced pancreatic cancer in order to examine possible
benefits from radiotherapy (RT) dose escalation as well as to propose possible
dose escalated fractionation schemes. METHODS: A modified linear quadratic (LQ)
model was used to fit clinical tumor response data from chemoradiation treatments
using different fractionations. Biophysical radiosensitivy parameters, a and
alpha/beta, tumor potential doubling time, Td, and delay time for tumor doubling
during treatment, Tk, were extracted from the fits and were used to calculate
feasible fractionation schemes for dose escalations. RESULTS: Examination of
published data from 20 institutions showed no clear indication of improved
survival with raised radiation dose. However, an enhancement in tumor response
was observed for higher irradiation doses, an important and promising clinical
Result with respect to palliation and quality of life. The radiobiological
parameter estimates obtained from the analysis are: alpha/beta = 10 +/- 3 Gy, a =
0.010 +/- 0.003 Gy-1, Td = 56 +/- 5 days and Tk = 7 +/- 2 days. Possible dose
escalation schemes are proposed based on the calculation of the biologically
equivalent dose (BED) required for a 50% tumor response rate. CONCLUSIONS: From
the point of view of tumor response, escalation of the administered radiation
dose leads to a potential clinical benefit, which when combined with normal
tissue complication analyses may Result in improved treatments for certain
patients with advanced pancreatic cancer. Based on this analysis, a dose
escalation trial with 2.25 Gy/fraction up to 69.75 Gy is being initiated for
unresectable pancreatic cancer at our institution. Partially supported by MCW
Cancer Center Meinerz Foundation.
PMID- 28517339
TI - SU-E-T-241: Proton Range Compared to the Treatment Planning Modeled Range.
AB - PURPOSE: To compare the range of the protons measured in the treatment room to
the range predicted by Xio. METHODS: Depth dose curves were measured using a
multi layer ionization chamber for various ranges and modulations. Ranges and
modulations were increased in one centimeter increments. The depth dose curves
were then analyzed and the measured range was determined. The range is defined as
the point where the distal edge of the depth dose curve is equal to 90% of the
average value of the dose across the spread out bragg peak. The measured range
was then compared to the range predicted by the treatment planning system. The
treatment planning system used was Xio. RESULTS: The maximum deviation was found
to be 1.6 mm, with the majority of range/modulation combinations falling under 1
mm. CONCLUSIONS: The difference in range being modeled by the treatment planning
system compared to the range measured in the teatment rooms is acceptable, and an
uncertainty of 1.5mm is used for treatment planning.
PMID- 28517340
TI - SU-E-T-210: Surviving a Visit by the Radiological Physics Center.
AB - PURPOSE: To demonstrate an objective approach to determining if a negative report
from the Radiological Physics Center (RPC) of greater than 10% error is valid or
has clinical significance. METHODS: The discrepancy involved the clinical
activity (mgRaEq) of Cs-137 sources, some manufactured by 3M and some by
Amersham. Measurements were made in the proprietary RPC Well Counter calibrated
by the MD Anderson ADCL and our Well Counter (CNMC, Model 44D) calibrated by the
same laboratory as well as the University of Wisconsin ADCL. In addition, we
possess an Amersham Cs-137 Check Source that had been calibrated by the UW-ADCL
in 2002. All clinical sources were checked in both Well Counters on the first
visit. One clinical source and the Check Source were measured in a second visit
that occurred 51 days later. RESULTS: On the initial RPC visit, 9 of 25 sources
had a minimum of an 8% discrepancy between the RPC and the Institution, with a
maximum of 11%. Contributing errors included using the incorrect straw position
by us, an unexplained 2.3% error in the RPC data identified 73 days post-visit, a
2% variation in Chamber Factors for our Well Counter from the two ADCL's. When we
use the 2004 value of Air Kerma Strength for the Check Source to determine a
Calibration Factor of the Well Counter, all sources were within 0.5% of their
decayed value established in 2002. CONCLUSIONS: This work emphasizes the value of
having simple Constancy Check systems in a Quality Assurance program as
'Accuracy' has error bars. The disagreement in calibration data between the ADCL
Laboratories, which was at the 2% maximum quoted in their Calibration Reports, is
a reminder that there is uncertainty in measurements. Constancy Checks allow one
to sort out discrepancies and to answer challenges to the validity of your
program.
PMID- 28517341
TI - SU-E-T-250: Dose-Response Curves for the Esophagus.
AB - PURPOSE: To determine the dose-response curve for the esophagus, using esophageal
thickening as a surrogate for radiation injury. METHODS: 15 esophageal cancer
patients were selected who had received weekly 4DCT images throughout their
course of concurrent chemo-radiotherapy (IMRT) to a total of 50.4Gy. Each patient
had a length of at least 4cm of esophagus that was outside the GTV but received
the full prescription dose. The weekly CT images were registered with the
original treatment planning CT images using deformable registration techniques,
and the esophagus contours mapped to the weekly images. The relative change in
esophagus size was calculated as the average ratio of the cross-sectional area of
the esophagus (minus air) in the weekly images to the area in the planning images
for a 1cm long region of the esophagus in the center of the CTV (i.e. away from
the GTV and field edge). We are considering this region to be 'normal esophagus.'
RESULTS: Thirteen of the 15 patients experienced mild esophagitis. The average
relative expansion increased as the treatment progressed. For all patients the
esophagus was thicker at the final week of treatment than its pre-treatment size.
For 7/15 patients the esophageal expansion was larger than 1.3. The average
relative expansion of the esophagus was 1.30+/-0.19 (range: 1.04 - 1.67). We will
present dose-response curves calculated from the weekly 4DCTs. CONCLUSIONS: The
esophagus expands in response to radiation, reaching approximately a 30% increase
in cross-sectional area during the final week of a 50.4Gy treatment, although
there is much variability between patients.
PMID- 28517342
TI - SU-E-T-220: A Web-Based Research System for Outcome Analysis of NSCLC Treated
with SABR.
AB - PURPOSE: To establish a web-based software system, an electronic patient record
(ePR), to consolidate and evaluate clinical data, dose delivery and treatment
outcomes for non small cell lung cancer (NSCLC) patients treated with
hypofractionated stereotactic ablative radiation therapy (SABR) across
institutions. METHODS: The new trend of information technology in medical imaging
and informatics is towards the development of an electronic patient record (ePR),
in which all health and medical information of each patient are organized under
the patient's name and identification number. The system has been developed using
the Wamp Server, a package of Apache web server, PHP and MySQL database to
facilitate patient data input and management, and evaluation of patient clinical
data and dose delivery across institution using web technology. The data of each
patient to be recorded in the database include pre-treatment clinical data,
treatment plan in DICOM-RT format and follow-up data. The pre-treatment data
include demographics data, pathology condition, cancer staging. The follow-up
data include the survival status, local tumor control condition and toxicity. The
clinical data are entered to the system through the web page while the treatment
plan data will be imported from the treatment planning system (TPS) using DICOM
communication. RESULTS: The collection of data of NSCLC patients treated with
SABR stored in the ePR is always accessible and can be retrieved and processed in
the future. The core of the ePR is the database which integrates all patient data
in one location. CONCLUSIONS: The web-based DICOM RT ePR system utilizes the
current state-of-the-art medical informatics approach to investigate the
combination and consolidation of patient data and outcome results. This will
allow clinically-driven data mining for dose distributions and resulting
treatment outcome in connection with biological modeling of the treatment
parameters to quantify the efficacy of SABR in treating NSCLC patients.
PMID- 28517343
TI - SU-E-T-260: Radiation Exposure Estimation for 131Cs Prostate Implant Patient
Release Determination.
AB - PURPOSE: Due to the short half-life and high energy of Cesium-131 (131Cs), the
exposure rate outside the patient could potentially increase radiation exposure
to hospital staff and exceed the maximum patient release exposure rate limit. A
calculation technique has been developed to estimate the exposure rate at 1 meter
from the patient, for prostate patients receiving 131Cs implants. METHODS: In our
calculation for each patient, all 131Cs sources were treated as one single
source, and the point on the prostate with the shortest distance to skin surface
was selected as the effective source position. Attenuation inside the patient was
calculated based on the attenuation coefficient of 30 keV photons in water,
assuming homogeneous patient density. This calculation technique was evaluated on
our first 25 131Cs implant patients. For comparison, the exposure rate at
approximately 1 meter inferior to patient perineum was measured prior to patient
release using the Inovision 451P-RYR survey meter. RESULTS: The distance from the
edge of the prostate to skin surface along the inferior direction was the
shortest in all 25 patients. The mean of the calculated exposure rates at 1 meter
from skin surface was 0.53 mR/hr, 0.53 mR/hr, 0.04 mR/hr, 0.04 mR/hr and 1.5
mR/hr along the anterior, posterior, left, right and inferior directions,
respectively. The mean of the measured exposure rate at 1 meter inferior to
patient perineum was 1.1 mR/hr. The mean ratio of the measured versus calculated
exposure rate was 0.74 (standard deviation = 0.23). CONCLUSIONS: Our calculation
technique is useful in determining in advance whether a patient may require
hospitalization after his implant. The exposure rate at 1 meter inferior to
patient perineum is a good indicator for determining whether the exposure rate
along any direction might exceed the maximum allowed patient release exposure
rate of 6 mR/hr.
PMID- 28517344
TI - SU-E-T-230: Field Factor Verification in Small Fields.
AB - PURPOSE: Small field is being commonly used in radiosurgery and IMRT, however
dosimetry is challenging due to source size, electronic disequilibrium and
detector size. Correction factor, K, has been published for a limited set of
detectors and beam energies. Validity of K for several detectors is investigated.
Also extrapolation ion chamber could be used using reciprocity theorem for small
fields which is attempted in this study. METHODS: Various small volume detectors:
IBA SFD, PTW TN60012 diode, and PTW Pinpoint N31006, Standard Imaging A16, along
with Nuclear Associate N2339IT extrapolation chamber were used to measure output
of square fields from 1*1 to 10*10 cm2 for Varian 6 and 16 MV beams. Measurements
were made in a water phantom at 1.5cm depth for 6MV photon and 3.0cm depth for
15MV photon with SSD 100cm. Extrapolation chamber was used in solid water.
Published correction factors (Francescon et al, MP, 2011)1, K were used for the
detectors used in this study. The K value was derived for extrapolation chamber
by modeling based on the difference between its detector output and the average
output factor from the diodes and pinpoints. RESULTS: The variation in output as
measured from different detector is significant (+/-7.0%) for field sizes = 3*3
cm2 and converges after large field sizes for both energies. The output factor
for the extrapolation chamber was out of range from diodes/pinpoints in both 6MV
and 16 MV beams. After applying detector K, the field size factors agree each
other within +/-2.2% for all field sizes. CONCLUSIONS: The value of K provides
reasonably good data for field factors irrespective of detector and the field
factors can be matched within 2.2%. A mathematical function for extrapolation
chamber also provides field factors comparable to the other detectors.
PMID- 28517345
TI - SU-E-T-245: Survival Fractions for Head-And-Neck Cancer Derived from Tumor-Volume
Variation Curves Using a 2-Level Cell Population Model.
AB - PURPOSE: Volumetric tumor response to radiotherapy is an integrated process which
includes several radiobiological mechanisms, such as cell killing, cell
proliferation, dead-cell removal and tumor reoxygenation. Our goal is to
reconstruct the information about these underlying radiobiological processes and
specifically the cell survival fractions by fitting a 2-level cell-population
tumor-volume model to imaging-derived tumor-volume variation curves obtained
during radiotherapy for head-and-neck cancer. METHODS: Modeling tumor-volume
during radiotherapy is a challenging problem because it is described by a sum of
exponentials; therefore, the problem of accurately fitting a model to measured
data is ill-posed. As an initial point of this research, we utilize a simplest 2
level cell-population tumor-volume model which separates the entire tumor-cell
population into oxygenated viable cells and oxygenated lethally damaged cells.
The 2-level cell population tumor model has the advantage of being conditionally
well-posed. We integrated this parameterized radiobiological model with a least
squares objective function and a simulated annealing optimization algorithm to
characterize individual patients' time-dependent tumor-volume regression rates.
The measured tumor-volume variation curves were taken from a clinical study on
tumor-volume variation during radiotherapy for 14 head-and-neck cancer patients
in which an integrated CT/linac system was used for tumor-volume measurements.
RESULTS: The 2-level tumor volume modeling is able to predict tumor behavior
throughout an entire treatment for 8 of 14 patients. The average survival
fraction 0.44 agrees very well with the published survival fraction of 0.45 for
the head-and-neck squamous cell carcinoma. However, the 2-level model cannot
describe the variation of the cell disintegration rate which is observed at the
end of treatment for some of the head-and-neck cancer patients. CONCLUSIONS: The
2-level cell population model is an acceptable approximation for the tumor-volume
for some clinical cases, but it cannot describe all tumor-volume regression
cases. This may be explained by omitting hypoxia in the 2-level model.
PMID- 28517346
TI - SU-E-T-214: Predicting Plan Quality from Patient Geometry: Feature Selection and
Inference Modeling.
AB - PURPOSE: To investigate and develop methods to infer treatment plan quality from
the geometric features of PTV/OAR structures; to discover and identify features
of high prognostic values. METHODS: This study explores the prognostic utility of
geometric features of two categories: (1) absolute geometry, characterizing the
volumes of single structures (PTV, OARs); and (2) relative geometry, based on the
minimal 3D distance and/or overlapping volume between pairs of structures. Using
prostate as a pilot site, we developed inference models to 'predict' SBRT plan
quality of DVH end points. We developed and assessed (1) a full linear regression
model based on both absolute and relative geometric features, (2) a sparsity
penalized linear regression model, (3) a linear regression model based on
absolute geometry features only; (4) a learning-based nonparametric model. Cross
validation was used for both selecting the parameter values as well as
quantifying the inference performance. The best inference method for each of the
DVH end points was identified to reveal the structural and prognostic differences
among them. RESULTS: For linear regression, using sparsity-regularization
discovered geometric features that were mostly absolute, demonstrating their
dominant linear prognostic utility. However, introducing relative geometric
features improved the plan quality prediction by 15% for all DVH end points. In
contrast, nonparametric models had a heavier dependence on relative geometry
features. While linear regression based on both features sets predicted OAR DVH
points slightly better, the nonparametric method excelled in predicting PTV
coverage and conformality. CONCLUSIONS: The inference result from this study
provides an 'expectation' for the plan quality before the planning is to be
performed, providing reference goals for the planner and a baseline for detecting
abnormality. The use of relative geometry complements the absolute geometry with
information on spatial configuration of the PTV/OAR structures of individual
patients, and the variation in achievable conformality as a consequence.
PMID- 28517347
TI - SU-E-T-223: High-Energy Photon Standard Dosimetry Data: A Quality Assurance Tool.
AB - PURPOSE: Describe the Radiological Physics Center's (RPC) extensive standard
dosimetry data set determined from on-site audits measurements. METHOD AND
MATERIALS: Measurements were made during on-site audits to institutions
participating in NCI funded cooperative clinical trials for 44 years using a
0.6cc cylindrical ionization chamber placed within the RPC's water tank.
Measurements were made on Varian, Siemens, and Elekta/Philips accelerators for 11
different energies from 68 models of accelerators. We have measured percent depth
dose, output factors, and off-axis factors for 123 different accelerator
model/energy combinations for which we have 5 or more sets of measurements. The
RPC analyzed these data and determined the 'standard data' for each model/energy
combination. The RPC defines 'standard data' as the mean value of 5 or more sets
of dosimetry data or agreement with published depth dose data (within 2%).
RESULTS: The analysis of these standard data indicates that for modern
accelerator models, the dosimetry data for a particular model/energy are within
i,+/-2%. The RPC has always found accelerators of the same make/model/energy
combination have the same dosimetric properties in terms of depth dose, field
size dependence and off-axis factors. Because of this consistency, the RPC can
assign standard data for percent depth dose, average output factors and off-axis
factors for a given combination of energy and accelerator make and model.
CONCLUSIONS: The RPC standard data can be used as a redundant quality assurance
tool to assist Medical Physicists to have confidence in their clinical data to
within 2%. The next step is for the RPC to provide a way for institutions to
submit data to the RPC to determine if their data agrees with the standard data
as a redundant check. This work was supported by PHS grants CA10953 awarded by
NCI, DHHS.
PMID- 28517349
TI - SU-E-T-207: Flatness and Symmetry Threshold Detection Using Statistical Process
Control.
AB - PURPOSE: AAPM TG-142 guidelines state that beam uniformity (flatness and
symmetry) should maintain a constancy of 1 % relative to baseline. The focus of
this study is to determine if statistical process control (SPC) methodology using
process control charts (PCC) of steering coil currents (SCC) can detect changes
in beam uniformity prior to exceeding the 1% constancy criteria. METHODS: SCCs
for the transverse and radial planes are adjusted such that a reproducibly useful
photon or electron beam is available. Transverse and radial - positioning and
angle SCC are routinely documented in the Morning Check file during daily warm
up. The 6 MV beam values for our linac were analyzed using average and range
(Xbar/R) PCC. Using this data as a baseline, an experiment was performed in which
each SCC was changed from its mean value (steps of 0.01 or 0.02 Ampere) while
holding the other SCC constant. The effect on beam uniformity was measured using
a beam scanning system. These experimental SCC values were plotted in the PCC to
determine if they would exceed the predetermined limits. RESULTS: The change in
SCC required to exceed the 1% constancy criteria was detected by the PCC for 3
out of the 4 steering coils. The reliability of the result in the one coil not
detected (transverse position coil) is questionable because the SCC slowly
drifted during the experiment (0.05 A) regardless of the servo control setting.
CONCLUSIONS: X-bar/R charts of SCC can detect exceptional variation prior to
exceeding the beam uniformity criteria set forth in AAPM TG-142. The high level
of PCC sensitivity to change may result in an alarm when in fact minimal change
in beam uniformity has occurred. Further study is needed to determine if a
combination of individual SCC alarms would reduce the false positive rate for
beam uniformity intervention. This project was supoorted by a grant from Varian
Medical Systems, Inc.
PMID- 28517348
TI - SU-E-T-234: LET Measurement Using Nuclear Emulsion and Monte Carlo Simulation for
Proton Beam.
AB - PURPOSE: The significant issue of particle therapy such as proton and carbon ion
biological effect on tumors and normal tissue. This effect closely connected with
linear-energy-transfer (LET). This work presents a Monte Carlo study using GEANT4
and the verification using Nuclear Emulsion to show LET for proton beam. METHODS:
National Cancer Center (NCC) has IBA Beam Nozzle and cyclotron for proton
therapy. We use proton beam bragg peak range 14cm. Also, we already developed the
simulation using GEANT4 and finished validation for scattering proton beam. In
our simulation, we make same condition with experimental setup.Nuclear emulsion
films interleaved with tissue equivalent absorbers can be fruitfully used to
reconstruct proton tracks with very high precision. This Nuclear emulsion film
has been supported from Nagoya University, analyzed in Pusan University, was
irradiated with a therapeutic proton beam at NCC. The Emulsion packs was located
at entrance and bragg peak region of proton. This position means low and high LET
region. The scanning of the emulsions has been performed at Nagoya University,
where a fully automated microscopic scanning technology has been developed for
the OPERA experiment on neutrino oscillations. RESULTS: We could see the
reconstructed track of proton scanning emulsion. From film scanning, we got the
LET distribution at low and high LET region for several proton tracks. Simulation
results was similar distribution within standard deviation in acceptance level.
Also we got the RBE distribution using LET measurement for proton beam.
CONCLUSIONS: We measured LET at entrance and bragg peak region using Monte Carlo
study and Nuclear Emulsion film, for NCC proton beam. This results means the good
observation of LET using the nuclear emulsion. And this method can be used
successfully in medical field.
PMID- 28517350
TI - SU-E-T-217: Automated Data Mining of Lung SBRT Cases for Predicting Dosimetric
Indices in Prospective Plans.
AB - PURPOSE: To develop an automated technique for evaluating lung stereotactic body
radiotherapy (SBRT) plan quality and predicting achievable lung dose constraints.
METHODS: We examined the workflow scripting capabilities of a radiation oncology
software package (MIM Software Inc) for automatically generating mean dose
gradients and overlap volume histograms (OVHs) for lung SBRT plans. Mean dose
gradients were created to assess plan quality by quantifying the dose fall-off
from the planning target volume (PTV) into the ipsilateral lung. OVHs were
created to evaluate potential predictors of achievable lung dose constraints by
measuring the amount of ipsilateral lung volume overlapping the uniformly
expanded PTV. Based on the knowledge that OVHs will depend on the size and
spatial relationship of the lung and PTV structures, we hypothesize that OVH
derived indices will therefore serve as predictors of achievable lung dose. The
workflow scripts were evaluated in a pilot study of 10 lung SBRT plans (50 Gy in
5 fractions) with varying PTV sizes and locations. RESULTS: The scripted
workflows were successful in automatically generating mean dose gradients and
OVHs for the PTV and ipsilateral lung. The workflows were able to produce the
aforementioned data in a matter of seconds (per patient), which would have
otherwise been excessively time consuming and labor intensive. From the pilot
study, the average mean dose gradient was - 4.1 +/- 0.6, indicating that all
evaluated patients had similar and acceptable plan quality. Furthermore, the OVH
data indicated that a 0 mm PTV expansion and a 10 mm PTV expansion correlated
with the mean lung dose (correlation coefficients of 0.71 and 0.56,
respectively). CONCLUSIONS: Our current data demonstrate that mean lung dose
correlates to multiple OVH indices. These results indicate that automated large
scale mining of retrospective data is a highly promising approach for predicting
dosimetric indices in prospective lung SBRT plans.
PMID- 28517351
TI - SU-E-T-246: Preliminary Normal Tissue Complication Probability (NTCP) Analysis
for Radiation Pneumonitis (RP) after Stereotactic Body Radiotherapy (SBRT).
AB - PURPOSE: NTCP analysis was performed with Lyman model to study the dose tolerance
limits for radiation-induced pneumonitis (RP) in hypofractionated SBRT. Since
SBRT is increasingly being applied for the treatment of large and central tumors,
it is important from a clinical point of view to determine the dose tolerance
limits for specific risk of toxicity. METHODS: Eighteen consecutive patients who
were treated using volumetric modulated arc therapy (RapidArc) for lung tumors
exceeding 80cc were assessed. The evaluation of toxicity was scored using Common
Toxicity Criteria AE4.0. Median follow-up time was 12.8 months. Clinical outcomes
have been published, and we performed an NTCP analysis to determine the
complication rate in relation to statistical dose tolerance limits. The dose
volume histogram (DVH) reduction techniques of the total lung V20Gy, V15Gy,
V10Gy, V5Gy and mean lung dose (MLD) were each analyzed, as well as the
ipsilateral lung V5Gy and the contralateral lung V5Gy. The framework of the Lyman
Model was used except that each DVH reduction method was analyzed independently
instead of using the power-law relationship for volume dependence. Model
parameters were fitted using the Maximum Likelihood technique. RESULTS: RP was
reported in 5 patients (CTC Grade 2 in 3, and Grade 3 in 2). Total lung V5Gy and
contralateral lung V5Gy were the best predictors of RP (p < 0.0001 for both). For
V5Gy, the 10% risk level for Grade 2-3 RP was 28.4% for total lung and 21.6% for
contralateral lung. CONCLUSIONS: Analysis of RP endpoints has identified total
lung V5Gy and contralateral lung V5Gy as the best predictors of RP following
RapidArc. These findings are based on limited clinical data, and longer follow-up
in larger patient cohorts is required in order to determine more accurate dose
tolerance limits. Dr. Grimm developed the DVH Evaluator, described at
www.DiversiLabs.com and distributed by www.LifeLineSoftware.com. The analysis
presented here is part of that software. Dr. Senan's department has received
research funding from Varian Medical Systems, and Dr. Senan has received speakers
honoraria from Varian.
PMID- 28517352
TI - SU-E-T-255: A Novel Rectal Obturator for Prostate Radiotherapy Improves the
Spatial Distribution of Dose and Reduces the Predicted Risk for Rectal Bleeding
and Subjective Sphincter Control.
AB - PURPOSE: To investigate the effects of an endorectal device during prostate
radiotherapy on the spatial distribution of dose to the ano-rectal region and
quantify implications for normal-tissue-complication probabilities. METHODS:
Twenty-three patients with localised prostate cancer, referred for external beam
radiotherapy had 2 CT scans acquired, without and with the rectal obturator
(ProSpare) in-situ. For each patient two dose distributions were generated, based
on both CT scans. Dose-surface maps for the rectal surface and the anal surface
were generated and mean dose as well as a spatial measure (circumference of the
dose distribution) were determined for all patients, with and without ProSpare.
Using previously published NTCP models, the effect of ProSpare on NTCP was
investigated for rectal bleeding and subjective sphincter control. RESULTS: In a
previous study subjective sphincter control correlated strongest with mean dose
and lateral extent at 53 Gy. The use of ProSpare resulted in a highly significant
reduction of the lateral extent at 53 Gy (p=0.006), mean dose (p=0.0009) and NTCP
according to the LKB model (p=0.002 for grade 2 and p=0.001 for grade >=1). In a
previous study we reported that rectal bleeding correlated most strongly with the
lateral extent at 55 Gy and presented the constraint that it should not exceed
42% of the circumference. Using ProSpare resulted in a significant reduction of
the lateral extent at 55 Gy (p=0.001) and significantly more patients met that
proposed constraint (p=0.047). ProSpare resulted in a significant reduction of
NTCP for grade-2 rectal bleeding (p=0.007) and a reduction for rectal bleeding
grade >=1 (p=0.053). CONCLUSIONS: ProSpare resulted in a significant reduction of
mean dose to the anal sphincter and a significant reduction of the lateral extent
at 55 Gy. This corresponded to a significant reduction in the predicted risk of
reporting subjective sphincter control and grade-2 rectal bleeding.
PMID- 28517354
TI - SU-E-T-209: Four-Dimensional Gamma Method for Dose-Guided Radiotherapy.
AB - PURPOSE: The technique known as 'Gamma Evaluation Method' was an effective
measure for dose distribution comparison; however, it could not be used for
accurate real-time verification because of the unstable systematic factors. To
reduce the errors induced by systematic factors and there was a requirement for
real-time dose verification in Dose-guided Radiotherapy (DGRT), the formula of
Gamma Method was improved, and four-dimensional(4D) Gamma Method was proposed.
METHODS: The gamma index, showing the deviation of two sets of dose
distributions, should remove the error caused by different treatment delivery
time to realize accurate real-time verification in Dose-guided Radiotherapy.
Besides dose and distance, the variable of time, which was proportional to
monitor unit (MU), was added to the formula. The criterion for acceptable
distribution was generally defined as a tolerance of the dose, the distance and
monitor unit. The algorithm was designed and realized using the tool of Microsoft
Visual C++ 6.0. RESULTS: Two typical five beam treatment plans of Conformal
Radiotherapy and Intensity-Modulated Radiotherapy were adopted to verify the
algorithm. The two-dimensional (2D) ionization chamber MatriXX was used to
measure the dose distribution. The verification for each beam was as follows: (1)
analyze the evaluation results of gamma method and the improved gamma method.
(2)Analyze the evaluation results of measured dose distributions at different
time with the same dosage .The result showed that there existed errors caused by
systematic factors before formula was improved. Improved method could obviously
reduce the error induced by systematic factors, meeting DGRT's requirement for
accurate real-time verification. The result could also be used to judge the
stability of the accelerator. CONCLUSIONS: The 4-dimensional gamma method could
reduce errors caused by systematic factors, and it could be used to reflect the
stability of different accelerators. Supported by the National Natural Science
Foundation under grant No.30900386 and the National Science Foundation of Anhui
Province (Nos.090413095 and111040606Q55).
PMID- 28517353
TI - SU-E-T-240: Accuracy of Dose Attenuation Correction for a 6D Carbon Fiber
Treatment Couch Using a Virtual Couch Technique Integrated into a Treatment
Planning System.
AB - PURPOSE: A commercial 6D carbon fiber radiotherapy treatment couch (Imaging Couch
Top, BrainLAB) has recently been reported to attenuate photon beams and increase
skin dose. To prevent skin toxicity and ensure the target dose, it is important
to correct the attenuation properties of the treatment couch with the treatment
planning system (TPS). In this study, we evaluated the accuracy of dose
attenuation correction by a virtual couch technique integrated into the TPS.
METHODS: A virtual couch was modeled in the TPS (Eclipse v10.0, Varian). The CT
value of the virtual couch was assigned with the CT value of the kilovoltage-CT
images of the treatment couch. A phantom consisting of several plastic water
slabs was created. We selected an evaluation point within the phantom on the
couch structure at a 9 cm depth from the couch surface, which was placed at the
isocenter. The doses at this point were calculated and measured at several gantry
angles, from 120 degree to 240 degree at 10 degree steps, and each field size was
10 cm * 10 cm. The prescribed dose was 100 monitor units for 6/10 MV photon beams
and 6 MV-SRS mode (Trilogy Tx, Varian). Dose measurements were performed with an
ion chamber. RESULTS: The largest difference between measured and calculated
doses was 3.3% for a gantry angle of 120 degree and 6 MV-SRS mode. The average
dose difference was within 1.6% for all gantry angles and photon beams. In the
case without attenuation correction, the largest difference was 8.2% and the
average difference was 5.2%. CONCLUSIONS: Use of the virtual couch technique in
TPS accomplished sufficient accuracy for dose attenuation correction of the 6D
carbon fiber treatment couch, and it is an effective method for clinical use.
PMID- 28517355
TI - SU-E-T-249: Theoretical Analysis of the Effects Uncertainties Have On Treatment
Outcomes.
AB - PURPOSE: Mathematical models are used in Industrial & Systems Engineering to
analyze complex integrated operational systems. Adapting this approach to
radiation therapy can help quantify the precision and accuracy necessary to
achieve optimal outcome of radiation treatment. The purpose of this work is to
develop such a model using clinical data and assess the effect uncertainties have
on treatment outcomes. METHODS: The Taguchi Loss Function (TLF) is adapted to
radiation therapy using conventional radiobiological models for tumor control
probabilities (TCP) and normal tissues complication probabilities (NTCP) based on
the equivalent uniform dose. The TCP and NTCP curves are combined to create a
failure probability function for a given treatment plan. The composite effects of
all uncertainties involved in treating a patient are modeled by a normal
distribution. The standard deviation and mean of the normal distribution
represent the precision and accuracy of a treatment. The failure probability
function is convolved with the normal distribution to arrive at an expected
failure probability. Precision was varied from 0.5% to 25% while accuracy ranged
from +/-5% to investigate uncertainties effects on complication-free local tumor
control. 3D 4-field box plans where compared to IMRT plans for 18 prostate
patients using this method. RESULTS: The average expected failure probability at
the prescription dose for the 3D 4-field box plans was 30.02% and 18.13% for the
IMRT plans at zero uncertainty. At 25% uncertainty the expected failure
probabilities were 76.85% and 64.36%, respectively. On average the IMRT plans
failure probability was 14.84% less than the 3D 4-field box plans for all
uncertainty levels. CONCLUSION: This study demonstrates that uncertainty in
radiotherapy procedures has a quantifiable effect on treatment outcome. To
further improve complication-free local tumor control we must both improve
treatment technologies and improve quality to minimize the uncertainties in
radiation therapy.
PMID- 28517356
TI - SU-E-T-219: A Free and Open Source DICOM Solution: DicomPack.
AB - PURPOSE: DicomPack aims to provide a Perl DICOM library to isolate DICOM
complexity and facilitate creation of DICOM applications. METHODS: DicomPack was
initially designed for research projects to process and exchange radiotherapy
medical images and treatment plans among research institutions, as well as
between treatment planning systems and Open Radiological Archiving and
Communication System (ORACS) research database. DicomPack uses an extensible
internal data structure to store any encoded information observing DICOM's
tag/element structure. Therefore, DicomPack either populates a data structure by
DICOM information or converts a populated data structure into DICOM format. In
this way, DicomPack creates a DICOM file either from scratch or using an existing
DICOM template upfront. And this design also enables DicomPack to handle nested
sequence data and multi-frame images easily. Along with DicomPack?IO,
DicomPack?Network provides a comprehensive solution of exchanging DICOM
information through DIMSE (DICOM Message Service) protocol. Its callback plugin
design provides a universal interface to all DIMSE commands (DIMSE-C and DIMSE
N). Each time a new DIMSE command needs to be implemented, users only need to
provide callback procedures to answer some basic questions, such as where to
retrieve/store DICOM information. In addition, DicomPack provides examples, e.g.,
DicomDumper, DicomAnonymizer, DicomStore, under DicomPack?Util to demonstrate how
to develop DICOM applications through DicomPack. RESULTS: Conclusions: DicomPack
is a pure Perl package, which means DicomPack only has dependency on core Perl
functions. As free software, DicomPack can be redistributed and/or modified as
Perl. The easiest way to install DicomPack is through cpan.org (Comprehensive
Perl Archive Network). However, DicomPack is in no way intended to to interpret
DICOM information and/or enforce DICOM conformance, which will be up to
application developers.
PMID- 28517357
TI - SU-E-T-259: A Statistical and Machine Learning-Based Tool for Modeling and
Visualization of Radiotherapy Treatment Outcomes.
AB - PURPOSE: Effective radiotherapy outcomes modeling could provide physicians with
better understanding of the underlying disease mechanism, enabling to early
predict outcomes and ultimately allowing for individualizing treatment for
patients at high risk. This requires not only sophisticated statistical methods,
but user-friendly visualization and data analysis tools. Unfortunately, few tools
are available to support these requirements in radiotherapy community. METHODS:
Our group has developed Matlab-based in-house software called DREES for
statistical modeling of radiotherapy treatment outcomes. We have noticed that
advanced machine learning techniques can be used as useful tools for analyzing
and modeling the outcomes data. To this end, we have upgraded DREES such that it
takes advantage of useful Statistics and Bioinformatics toolboxes in Matlab that
provide robust statistical data modeling and analysis methods as well as user
friendly visualization and graphical interface. RESULTS: Newly added key features
include variable selection, discriminant analysis and decision tree for
classification, and k-means and hierarchical clustering functions. Also, existing
graphical tools and statistical methods in DREES were replaced with a library of
the Matlab toolboxes. We analyzed several radiotherapy outcomes datasets with our
tools and showed that these can be effectively used for building normal tissue
complication probability (NTCP) and tumor control probability (TCP) models.
CONCLUSIONS: We have developed an integrated software tool for modeling and
visualization of radiotherapy outcomes data within the Matlab programming
environment. It is our expectation that this tool could help physicians and
scientists better understand the complex mechanism of disease and identify
clinical and biological factors related to outcomes.
PMID- 28517358
TI - SU-E-T-229: Monte Carlo Dosimetric Study of SAVI HDR Applicator for Partial
Breast Irradiation.
AB - PURPOSE: To investigate the dosimetric variation by Monte Carlo and
experimentally simulating the situation with and without tissue invagination and
the potential translation and rotation of the SAVI applicator for partial breast
irradiation. METHODS: The SAVI applicator with the cavity filled with air and
water was merged into a water phantom and the delivered dose was simulated by
MCNP monte carlo program. The results verified using an ion chamber and film were
compared with a homogenous dose calculation by the treatment planning system. A
dose variation from the SAVI translational shift was simulated and measured by
moving an ion chamber along with the central axis direction. A dose change from
the SAVI rotation was simulated and measured by placing an ion chamber at a fixed
point while rotating the SAVI device about the central axis. RESULTS: The
dosimetric variations for the SAVI device were found to be related to the cavity
dimension, source arrangement, and dwell times. For the single dwell source
placed in the center of the applicator, the maximum difference of the dose with
the air cavity at 1cm away from the air-water boundary is about 7% higher than
that with water filling in the cavity. But the simulation and measurements with
nearly fully loaded multi-sources for the same situation show a difference of
less than 3%. The 3% dose variation in average was found from either the 3 mm
translation or 3 degree rotation of the SAVI applicator. CONCLUSIONS: The maximum
dosimetric effect of an air cavity is 7% off compared with a water filled cavity
when a single dwell source position is used in the center of the central
catheter. Multiple catheters of the SAVI applicator with a nearly fully loaded
dwell source position produce the discrepancy of less than 3% and allow for
optimal and conformal dose distribution to a lumpectomy cavity while minimizing
the dose to adjacent normal structures.
PMID- 28517359
TI - SU-E-T-244: High Spatial Resolution EBT2 Film Dosimetry.
AB - PURPOSE: The purpose of this study was to measure depth dose curves and dose
effects near high-Z interfaces with radiochromic EBT-2 films reaching a spatial
resolution superior to conventional methods with no quality losses. METHODS: The
setup is made of two 12cm stacks of RW3, fixing an EBT2 film in a vertical
position. To measure a depth dose curve, the setup was irradiated with a 15MV
photon beam (Siemens Primus). Since the film is positioned parallel to the beam
propagation, the depth dose curve is measured with only one film per depth.
Additionally, a dental gold alloy probe was inserted in the RW3 stack at 6cm
depth and the dose enhancement in front of the probe was measured with the method
described above. Hereby, the bottom edge of the film touches the probe's
surface.The irradiated films were digitized with a resolution of 72dpi using an
Epson 10000XL flatbed scanner with a transparency unit and alignment frames. With
this setup, the spatial resolution is only limited by the scanning resolution.
RESULTS: In order to verify the new measurement method, comparisons of the
measured depth dose curves with the conventional method of placing the film
orthogonal to the beam propagation showed deviations of lesser than 3%.The
comparison of the dental gold measurements with Monte Carlo simulations shows a
systematic lower measured dose which is still within 5% consistency. However
attention has to be paid in the experimental setup and film preparation.
CONCLUSIONS: The introduced method shows significant advantages to conventional
orthogonal EBT2 film positioning. It shows a very high spatial resolution and the
area of interest is only limited by the film size. The method will be used in
further studies, to investigate dose profiles and dose effects near interfaces
and in inhomogeneities.
PMID- 28517360
TI - SU-E-T-213: Development of a Web Wrapper to Facilitate Radiotherapy Research.
AB - PURPOSE: Researchers write many computer programs with unique implementations,
usually requiring a great amount of effort for other researchers to learn how to
install, configure, and use. Some programs require specialized hardware platforms
such as GPU workstation or CPU cluster, which may not readily available for many
researchers. This work develops a general web platform to 'wrap' radiotherapy
software tools into a user friendly, browser-based interface. METHODS: We
developed a web wrapper based on existing technologies (e.g. HTML5, JavaScript,
PHP, Python, XML) to interface with command line-based research tools. This
wrapper enables users to easily perform various tasks in any modern web browser,
while underlying tools are launched remotely. Visitors can upload data, configure
settings, process data remotely, then view, share, and download results with
minimal effort. This web wrapper is developer friendly; new tools are easily
integrated by editing XML configuration files. RESULTS: As a test case, we have
successfully wrapped a set of command line tools, developed by our group, into a
single web app, providing fluence map generation, CT image processing, and GPU
based Monte Carlo (MC) dose calculation. The result is a web-based quality
assurance tool. With this tool, users can upload compressed DICOM-RT files,
recompute dose using the MC method, and evaluate the results by viewing dose
distribution, 3D gamma index distribution and DVH curves. The entire work-flow
can be completed within 2 minutes provided users have a reasonable Internet
connection speed. CONCLUSIONS: We have developed an web wrapper to increase the
accessibility of radiotherapy tools and reduce users' learning curve through a
friendly web-based interface. This work also allows quick and easy deployment and
distribution of software tools developed by researchers to the whole community.
PMID- 28517361
TI - SU-E-T-222: How to Define and Manage Quality Metrics in Radiation Oncology.
AB - PURPOSE: Since the 2001 IOM Report Crossing the Quality Chasm: A New Health
System for the 21st Century, the need to provide quality metrics in health care
has increased. Quality metrics have yet to be defined for the field of radiation
oncology. This study represents one institutes initial efforts defining and
measuring quality metrics using our electronic medical record and verify
system(EMR) as a primary data collection tool. This effort began by selecting
meaningful quality metrics rooted in the IOM definition of quality (safe, timely,
efficient, effective, equitable and patient-centered care) that were also
measurable targets based on current data input and workflow. METHODS: Elekta
MOSAIQ 2.30.04D1 was used to generate reports on the number of Special Physics
Consults(SPC) charged as a surrogate for treatment complexity, daily patient time
in department(DTP) as a measure of efficiency and timeliness, and time from CT
simulation to first LINAC appointment(STL). The number of IMRT QAs delivered in
the department was also analyzed to assess complexity. RESULTS: Although initial
MOSAIQ reports were easily generated, the data needed to be assessed and adjusted
for outliers. Patients with delays outside of radiation oncology such as
chemotherapy or surgery were excluded from STL data. We found an average STL of
six days for all CT-simulated patients and an average DTP of 52 minutes total
time, with 23 minutes in the LINAC vault. Annually, 7.3% of all patient require
additional physics support indicated by SPC. CONCLUSIONS: Utilizing our EMR, an
entire year's worth of useful data characterizing our clinical experience was
analyzed in less than one day. Having baseline quality metrics is necessary to
improve patient care. Future plans include dissecting this data into more
specific categories such as IMRT DTP, workflow timing following CT-simulation,
beam-on hours, chart review outcomes, and dosimetric quality indicators.
PMID- 28517362
TI - The Absence of Quadrupolar Nuclei Facilitates Efficient 13 C Hyperpolarization
via Reversible Exchange with Parahydrogen.
AB - Nuclear spin hyperpolarization techniques are revolutionizing the field of 13 C
molecular MRI. While dissolution dynamic nuclear polarization (d-DNP) is
currently the leading technique, it is generally slow (requiring ~1 h) and costly
(~$USD106 ). As a consequence of carbon's central place in biochemistry,
tremendous progress using 13 C d-DNP bioimaging has been demonstrated to date
including a number of clinical trials. Despite numerous attempts to develop
alternatives to d-DNP, the competing methods have faced significant translational
challenges. Efficient hyperpolarization of 15 N, 31 P, and other heteronuclei
using signal amplification by reversible exchange (SABRE) has been reported in
2015, but extension of this technique to 13 C has proven to be challenging. Here,
we present efficient hyperpolarization of 13 C nuclei using micro-Tesla SABRE. Up
to ca. 6700-fold enhancement of nuclear spin polarization at 8.45 T is achieved
within seconds, corresponding to P13C ~4.4 % using 50 % parahydrogen (P13C >14 %
would be feasible using more potent ~100 % parahydrogen). Importantly, the 13 C
polarization achieved via SABRE strongly depends not only upon spin-lattice
relaxation, but also upon the presence of 15 N (I=1/2) versus quadrupolar 14 N
(I=1) spins in the site binding the hexacoordinate Ir atom of the catalytic
complex. We show that different 13 C nuclei in the test molecular frameworks
pyridine and acetonitrile-can be hyperpolarized, including 13 C sites up to five
chemical bonds away from the exchangeable hydrides. The presented approach is
highly scalable and can be applied to a rapidly growing number of biomolecules
amendable to micro-Tesla SABRE.
PMID- 28517363
TI - Cleave but not leave: Astrotactin proteins in development and disease.
AB - Over the years, animal studies have identified astrotactins as important membrane
proteins for glial-guided neuronal migration during central nervous system
development and hair follicle polarity control during skin development.
Biochemical studies have revealed intramembrane proteolysis as an important
feature of astrotactins. The two fragments of astrotactins remain linked together
by a disulfide bond after the proteolytic cleavage. In humans, mutations in
astrotactin genes have also been linked to a wide range of diseases, including
several developmental brain disorders, neurodegenerative diseases and cancer. In
this review, I will summarize the current knowledge of the biological function of
astrotactins in development, highlight the linkage between mutations in
astrotactin genes and human disease and discuss several outstanding questions
that remain unanswered. (c) 2017 IUBMB Life, 69(8):572-577, 2017.
PMID- 28517364
TI - A cryptic pigment biosynthetic pathway uncovered by heterologous expression is
essential for conidial development in Pestalotiopsis fici.
AB - Spore pigmentation is very common in the fungal kingdom. The best studied pigment
in fungi is melanin which coats the surface of single cell spores. What and how
pigments function in a fungal species with multiple cell conidia is poorly
understood. Here, we identified and deleted a polyketide synthase (PKS) gene
PfmaE and showed that it is essential for multicellular conidial pigmentation and
development in a plant endophytic fungus, Pestalotiopsis fici. To further
characterize the melanin pathway, we utilized an advanced Aspergillus nidulans
heterologous system for the expression of the PKS PfmaE and the Pfma gene
cluster. By structural elucidation of the pathway metabolite scytalone in A.
nidulans, we provided chemical evidence that the Pfma cluster synthesizes DHN
melanin. Combining genetic deletion and combinatorial gene expression of Pfma
cluster genes, we determined that the putative reductase PfmaG and the PKS are
sufficient for the synthesis of scytalone. Feeding scytalone back to the P. fici
DeltaPfmaE mutant restored pigmentation and multicellular adherence of the
conidia. These results cement a growing understanding that pigments are essential
not simply for protection of spores from biotic and abiotic stresses but also for
spore structural development.
PMID- 28517365
TI - Enantioselective dissipation of pyriproxyfen in soils and sand.
AB - Under normal conditions, the environmental behaviors of pesticides are affected
by complex environmental factors and the manner of administration together with
constraints. In order to meet the actual needs, we imitated the experiment and
found that the degradation rate of pyriproxyfen in soils rendered complex
changes. Rac-pyriproxyfen was successfully chiral separated on an AZ-H column and
the residue analysis method was in accord with the demand of pesticide analysis.
The results indicated that pyriproxyfen dissipated at a faster rate in
Heilongjiang soil and Hainan soil, while at a much slower speed in another three
soils and sand. Obvious enantioselective degradation was observed in Hainan soil
and Qingdao sand. The results suggested that pyriproxyfen alone had low
persistence in soil, but the moisture, soil type, the use of mixture formulation,
and second spraying treatment could play important roles in dissipation of
pyriproxyfen. Too large and too small moisture content could both make
pyriproxyfen persist for a longer period in soil than in soil with 25% moisture
content. Residues dissipated much slower after using Ai Qiu, while Shi Dingkang
did not have a big effect on degradation, with only a small acceleration effect.
Pyriproxyfen also dissipated in Hainan soil with difficulty after the second
treatment.
PMID- 28517366
TI - Genie in a blotter: A comparative study of LSD and LSD analogues' effects and
user profile.
AB - OBJECTIVE: This study aimed to describe self-reported patterns of use and effects
of lysergic acid diethylamide (LSD) analogues (AL-LAD, 1P-LSD, and ETH-LAD) and
the characteristics of those who use them. METHODS: An anonymous self-selected
online survey of people who use drugs (Global Drug Survey 2016; N = 96,894),
which measured perceived drug effects of LSD and its analogues. RESULTS: Most LSD
analogue users (91%) had also tried LSD. The proportion of U.K. and U.S.
respondents reporting LSD analogue use in the last 12 months was higher than for
LSD only. LSD analogue users described the effects as psychedelic (93%), over
half (55%) obtained it online, and almost all (99%) reported an oral route of
administration. The modal duration (8 hr) and time to peak (2 hr) of LSD
analogues were not significantly different from LSD. Ratings for pleasurable
high, strength of effect, comedown, urge to use more drugs, value for money, and
risk of harm following use were significantly lower for LSD analogues compared
with LSD. CONCLUSIONS: LSD analogues were reported as similar in time to peak and
duration as LSD but weaker in strength, pleasurable high, and comedown. Future
studies should seek to replicate these findings with chemical confirmation and
dose measurement.
PMID- 28517367
TI - Rationale and design of a randomized trial to assess the safety and efficacy of
MultiPoint Pacing (MPP) in cardiac resynchronization therapy: The MPP Trial.
AB - BACKGROUND: Although the majority of Class III congestive heart failure (HF)
patients treated with cardiac resynchronization therapy (CRT) show a clinical
benefit, up to 40% of patients do not respond to CRT. This paper reports the
design of the MultiPoint Pacing (MPP) trial, a prospective, randomized, double
blind, controlled study to evaluate the safety and efficacy of CRT using MPP
compared to standard biventricular (Bi-V) pacing. METHODS: A maximum of 506
patients with a standard CRT-D indication will be enrolled at up to 50 US
centers. All patients will be implanted with a CRT-D system (Quartet LV lead
Model 1458Q with a Quadra CRT-D, Abbott) that can deliver both MPP and Bi-V
pacing. Standard Bi-V pacing will be activated at implant. At 3 months
postimplant, patients in whom the echocardiographic parameters during MPP are
equal or better than during Bi-V pacing are randomized (1:1) to either an MPP or
Bi-V arm. RESULTS: The primary safety endpoint is freedom from system-related
complications at 9 months. Each patient's response to CRT will be evaluated using
a heart-failure clinical composite score, consisting of a change in NYHA
functional class, patient global assessment score, HF events, and cardiovascular
death. The primary efficacy endpoint is the proportion of responders in the MPP
arm compared with the Bi-V arm between 3 and 9 months. CONCLUSION: This trial
seeks to evaluate whether MPP via a single quadripolar LV lead improves
hemodynamic and clinical responses to CRT, both in clinical responders and
nonresponders.
PMID- 28517368
TI - Testicular thermoregulation, scrotal surface temperature patterns and semen
quality of water buffalo bulls reared in a tropical climate.
AB - This study evaluated the capacity of thermoregulation and its consequences on the
scrotal surface temperature patterns and semen quality of buffalo bulls raised in
a wet tropical climate. Eleven water buffaloes were evaluated in the rainiest, in
the transitional and in the less rainy season. Air temperature and humidity were
consistently high, but the animals did not show thermal stress in any season. The
scrotal temperature gradient of buffalo bulls using infrared thermography was
described, and three parallel and decreasing thermal bands were characterised.
Sperm quality (n = 176 ejaculates) was maintained in normal parameters over the
periods. Pearson's coefficients showed that sperm volume and progressive motility
were negatively correlated with ocular globe, epididymal tail and minimum scrotal
temperatures (p < .01). Sperm membrane integrity was negatively influenced by
increases in epididymal tail and minimum scrotal temperatures (p < .01). Ocular
globe temperature also showed positive correlation with rectal, spermatic cord,
and epididymal tail temperatures (p < .01). Therefore, even under high
temperature and humidity, the thermoregulatory system was effective in preventing
heat stress and the normality of scrotal surface temperatures, spermatogenesis
and sperm maturation were maintained.
PMID- 28517369
TI - Treatment of primary biliary cholangitis ursodeoxycholic acid non-responders: A
systematic review.
AB - BACKGROUND: Primary biliary cholangitis (PBC), formerly known as primary biliary
cirrhosis, is a chronic cholestatic liver disease characterized by an immune
mediated destruction of intrahepatic bile ducts. Ursodeoxycholic acid (UDCA) has
been the primary medication for the treatment of PBC, resulting in improved liver
tests, resolution of symptoms and increased transplant free survival. However,
not all patients respond to UDCA. The aim of this systematic review is to provide
an evidence based assessment of the medications that have been studied in
patients who are refractory to UDCA. METHODS: We performed a systematic
literature search on MEDLINE and the Cochrane Database of Systematic Reviews of
the published literature. A total of 23 articles fulfilling our inclusion
criteria were found. RESULTS: Several studies have shown an improvement in liver
biochemistries with the use of obeticholic acid in conjunction with UDCA.
Fibrates, including fenofibrate and bezafibrate, have evidence supporting benefit
in this population but need more robust studies to confirm these observational
results. Neither obeticholic acid nor fibrates have shown to increase transplant
free survival. While there may be some benefit with methotrexate, colchicine,
budesonide, mycophenolate mofetil and azathioprine, these findings were not
consistent and the benefits were marginal. Further investigation is needed.
CONCLUSION: In patients with PBC refractory to UDCA, obeticholic acid or a
fibrate is a reasonable choice as an adjunctive treatment to UDCA. Further
investigation with randomized controlled trials is needed to provide high quality
evidence to formulate standardized therapies in this difficult to treat
population.
PMID- 28517370
TI - Evaluation of dietary methionine requirement of male Korean native ducks for 3
weeks post-hatching.
AB - A total of 336 1-day-old male Korean native ducks (KND) were used in a completely
randomized design with seven dietary methionine levels (0.30-0.90% with 0.1%
increment) to determine the methionine requirement of male Korean native ducks
for 3 weeks after hatching. Each dietary treatment had six replicates with eight
ducklings per pen. One duckling from each pen (n = 6) was sacrificed to weigh
empty body and drumsticks at the end of the experiment. Final body weight and
weight gain of 3 weeks old KND were increased with increasing dietary methionine
levels up to 0.4%, and then decreased (P < 0.05) with a further increasing
dietary methionine level. In contrast, feed conversion ratio of the KND decreased
up to 0.4% and increased (P < 0.05) with the increasing dietary methionine level.
Both empty body weight and proportions of empty body weight were linearly
increased (P < 0.05) while the dietary methionine level elevated up to 0.4%.
Estimated dietary methionine requirement for maximum body weights, daily gain and
minimum feed conversion ratio were 0.36, 0.39 and 0.40%, respectively, when it
was fitted into linear- and quadratic-plateau models.
PMID- 28517371
TI - See one, do one, teach...a lifetime.
PMID- 28517372
TI - Multicenter verification of the Sysmex XN-Series.
AB - INTRODUCTION: Verification of hemocytometry equipment deviates significantly from
that of clinical chemistry equipment due to the absence of appropriate control
material and the need for fresh material. In practice, verification is limited to
comparison with the previously used equipment and determination of
reproducibilities. Particularly in multicenter settings, harmonization of results
is necessary. If the same equipment is used in several laboratory departments,
calibration and uniformity are important issues. METHODS: In this study, seven
Sysmex XN hematology modules distributed over three laboratories were evaluated
with the same set of samples (n=160). RESULTS: Results of each Sysmex XN
hematology module were compared with the results of the Sysmex XE-2100 hematology
analyzer using linear regression. Although excellent correlation coefficients
were obtained, in many cases the criteria for slope and/or intercept were not
met. Therefore, the same data were analyzed with Bland-Altman difference plots
with three times the specified CV% of the parameter as limits of agreement. At
least 90% of the determinations per parameter and per module must comply with
those limits of agreement. Almost all parameters on each module fulfilled these
criteria, and only RBC and Ht from respectively two and four XN modules had to be
recalibrated. Reproducibility of each parameter was determined 10 times in
patient samples with low, normal, and high levels. Reproducibility of all
parameters was within the specifications of the manufacturer and the biological
variability. CONCLUSION: With this straightforward method, all seven Sysmex XN
hematology modules demonstrated uniform results, which were identical to those of
the previously used Sysmex XE-2100 hematology analyzer, the performance of which
was well known.
PMID- 28517374
TI - SU-E-E-02: The Use of Social Media in a Medical Physics Classroom.
AB - PURPOSE: The purpose of this presentation is to provide an example of how
Facebook has been used in a medical physics classroom. METHODS: Facebook was used
in an introductory course in radiation interactions taken by graduate students in
a CAMPEP-accredited medical physics program. Facebook served two major functions
in the class, as a means for communicating announcements to students, and as a
forum for discussion of unclear points in the course. At the end of every class,
students were prompted to fill out a questionnaire asking them to identify points
that were not clear. After class, all questions were posted by the instructor (so
students maintained anonymity and did not have to be embarrassed by lack of
knowledge). Students had 24 hr to post responses to their peers' questions.
Students who responded correctly to peers' questions received additional in-
class credit for their response, thus encouraging them to respond. After 24 hr,
the instructor or a teaching assistant posted a response to the question.
RESULTS: 12/16 students participated in discussions. The students who did not
respond were all postdoctoral fellows (3/4 foreign) auditing the course. From 3
to 9 students typically responded to questions. Students responding to questions
received credit for their responses (0.4 points per response up to a maximum of 5
points added to an in-class grade that counted for 10% of their final grade).
Student evaluations of the use of Facebook were generally positive. Furthermore,
use of Facebook for this application extended the time students were interacting
with each other in medical physics. CONCLUSIONS: The use of social media in a
medical physics classroom appears to be an effective tool to incorporate into a
teaching methodology.
PMID- 28517373
TI - SU-D-217A-03: Nuclear Medicine Uniformity Assessment Using 2D Noise Power
Spectrum.
AB - PURPOSE: Nuclear medicine quality control programs require daily evaluation for
the presence of potential non-uniformities by commonly utilizing a traditional
pixel value-based assessment (Integral CFOVUniformity). While this method
effectively captures regional non- uniformities in the image, it does not
adequately reflect subtle periodic structures that are visually apparent and
clinically unacceptable, therefore requiring the need for additional visual
inspection of the image. The goal of this project was to develop a new uniformity
assessment metric by targetingstructural patterns and more closely correlating
with visual inspection. METHODS: The new quantitative uniformity assessment
metric is based on the 2D Noise Power Spectrum (NPS). A full 2D NPS was performed
on each image. The NPS was thresholded to remove quantum noise and further
filtered by the visual response function. A score, the Structure Noise Index
(SNI), was then applied to each based on the average magnitude of the structured
noise in the processed image. To verify the validity of the new metric, 50 daily
uniformity images with varying degrees of visual structured and non-structured
non-uniformity were scored by 5 expert nuclear medicine physicists. The
correlation between the visual score and SNI were assessed. The Integral CFOV was
also compared against the visual score. RESULTS: Our new SNI assessment metric
compared to the Integral CFOV showed in increase in sensitivity from 67% to 100%
in correctly identifying structured non-uniformities. The overall positive
predictive value also increased from 55% to 72%. CONCLUSIONS: Our new uniformity
metric correlates much more closely with visual assessment of structured non-
uniform NM images than the traditional pixel-based method. Using this new metric
in conjunction with the traditional pixel value-based assessment will allow a
more accurate quantitative assessment of nuclear medicineuniformity.
PMID- 28517375
TI - SU-D-218-01: Support Vector Machine Tissue Classification of Multiparametric MRI
Tumor Data.
AB - PURPOSE: To test the accuracy of Support Vector Machines in the classification of
Glioblastoma Multiforme tumor voxels usingmultiparametric MRI data. METHODS:
Various MRI scans were collected from patients with recurrent GBM. Each scan
session collected post-contrastT1(+C T1), T2, diffusion, perfusion, and multi
echo hypoxia images. Thediffusion-weighted images were converted to Apparent
Diffusion Coefficient (ADC) maps. The perfusion images were corrected for leakage
and represented as corrected rCBV maps. All of these scans were co-registered to
each other, giving an input matrix to our support vector machine consisting of
roughly 13,000 voxels, each with 5 feature values (+C T1, T2, ADC, rCBVcorrected,
delta T2*). The SVM was then trained usingradiologist confirmed labels for
'cyst', 'tumor', and 'normal tissue'. These labels were obtained using
longitudinal data as well as clinical scans, and tested on new data to determine
the accuracy of classifying tumor and cyst voxels. RESULTS: The tumor model
resulted in a specificity of 0.9841 and a sensitivity of 0.7498. The cyst model
resulted in a specificity of 0.9825 anda sensitivity of 0.9414. Both models
showed improvement with increasing features. CONCLUSIONS: These results show that
the SVM is capable of classifying tumor and cyst voxels in a single case study.
Aside from optimizing the current tumor model, future work will focus on the
potential for the SVM to help in early detection of recurrence. In order to
achieve this,we will need to test SVMs across patients. If we truly aim for early
detection, then we need to prove that the algorithm can be trained on a pool of
subjects with recurrent disease, and then test that model on a new patient before
recurrence is obvious.
PMID- 28517376
TI - SU-D-BRCD-04: Validation of Film Dosimetry in the Dose Build-Up Region.
AB - PURPOSE: To establish a film dosimetric method for high-resolution measurement in
the dose build-up region. METHODS: Percent depth dose (PDD) curves were measured
in water for TomoTherapy using Gafchromic EBT2 films. Depth dose measurements
were also performed using Standard Imaging A1SL and PTW PinPoint ionization
chambers, as well as a PTW DiodeE detector. The film and detector measurements
were then compared to Monte Carlo (MC) simulation data computed using PENELOPE.
An in- house support apparatus was constructed to hold the films parallel to the
beam central axis while being suspended in the water, simultaneously demarcating
the water surface on the film. The films were converted to dose using a corrected
net optical density method involving the red and blue color channels of an Epson
Expression 10000XL scanner. Film analysis was performed using ImageJ software and
MATLAB code developed in clinic. RESULTS: In our film method, a systematic shift
of 1.2mm downstream is seen for the sample of five films, with good
reproducibility within the sample (s=0.3mm). The film measurements showed a mean
PDD difference of 0.3% (s=0.4%) with a maximum of 1.3% from that of MC between
depths of 0.5mm to 20mm. The average film dose measured at the water surface
(d=0mm) was 13.1% greater than that calculated by MC. EBT2 film shows much better
agreement with MC in the dose build-up region than the ionization chamber and
detector measurements. CONCLUSIONS: This study demonstrates the capability of
EBT2 films for simple and accurate superficial dose measurements. A suspected
reason for the systematic shift in film alignment is attributed to difficulty in
determining water surface due to the meniscus that forms at the film. Funded by
SSRMP Research Grant 2011.
PMID- 28517377
TI - SU-D-BRA-03: Simultaneous MV-KV Imaging for Intra-Fractional Motion Management
during Volume Modulated Arc Therapy (VMAT) Delivery on the Varian TrueBeam.
AB - PURPOSE: To evaluate a MV-kV intra-fractional imaging technique for use during
volume modulated arc therapy (VMAT) with the Varian TrueBeam. METHODS: MV-kV
image pairs were acquired intra-fractionally during VMAT delivery. kV images (11
fps) were acquired throughout delivery using a standard pre-programmed imaging
template. MV images (9.5 fps) were acquired simultaneously by deploying the EPID
and passively collecting the resulting images using Varian proprietary software,
iTools Capture. Localization accuracy was evaluated by imaging a Rando phantom
implanted with 3 fiducials while moving the couch according to XML- programmed
trajectories simulating typical prostate and respiratory motion. VMAT delivery
was done using a single 360 degree arc in TrueBeam Developer mode. The effect on
accuracy of total MU and gantry speed was studied. To improve image quality, MV
frame averaging was performed and the MV and kV images were then registered to
their corresponding DRRs using in-house registration software. From these 2D
registrations, the 3D position at each MV-kV acquisition point was determined.
RESULTS: Between 130 and 390 MV-kV pairs were acquired for each delivery. The
mean difference between planned couch and measured fiducial 3D positions with
prostate motion was less than 0.03 cm in each direction (SD 0.03 cm). Neither
gantry speed nor MU significantly impacted accuracy. for respiratory motion, the
mean difference between planned and measured position was less than 0.04 cm.
Standard deviation averaged 0.06 cm but increased to 0.12 cm with large
instantaneous motion and less MV dose per frame. MV frame averaging and
inaccuracies in MV image gantry angle determination also affected accuracy,
particularly with significant motion. CONCLUSIONS: With high quality MV imaging,
MV-kV localization techniques can be highly accurate, even in the presence of
significant motion. As clinical MV-kV methods become available, such techniques
can provide an efficient and accurate method for monitoring intra-fractional
motion. This work was partially supported through a research agreement with
Varian Medical Systems, Palo Alto, CA.
PMID- 28517378
TI - SU-D-217BCD-01: Corrupted DICOM Image Recovering: A Clinical Experience.
AB - PURPOSE: Colored DICOM secondary capture images generated from CT perfusion
studies were corrupted if they were sent directly from a Siemens acquisition
workstation to a GE viewing workstation. However, those images were properly
displayed in the GE viewing workstation if they were transferred through a GE
PACS first. The purpose of this work is to investigate the cause of image
corruption and determine why passing through PACS corrected it. METHODS: DICOM
headers of corrupted and non-corrupted (sent through the PACS) images were
compared with a free DICOM software tool (http://DVTK.org); the differences were
highlighted. Certain header tags were found in non-corrupted images, but not in
corrupted images. These tags were sequentially removed until the non- corrupted
image became corrupted. Once a candidate tag was found, fresh corrupt images were
modified by adding a 'repair' tag and tested. RESULTS: It was found that the
absence of Planar Configuration (0028, 0006) is the cause of image corruption.
This attribute is used in the DICOM color image to specify whether the color
pixel data are sent color-by-plane or color-by- pixel and should be present if
the Sample per Pixel (0028, 0002) tag has a value greater than 1. In our DICOM
color images, the values of (0028, 0002) and Photometric Interpretation (0028,
0004) are 3 and RGB, respectively. Thus (0028, 0006) should equal 0 (color-by
pixel), which is used for uncompressed or lossless compressed transfer syntaxes.
Adding this tag and setting the value to zero manually repaired corrupt images.
CONCLUSIONS: Using open source DICOM tools and following the described process
can be a valuable ally in the search for causes of image corruption. Comparing
the headers and finding the handful of different tags rapidly led to an
explanation that could be used by the vendor for a permanent fix.
PMID- 28517379
TI - SU-D-213AB-03: Design Optimization of a HDR Ir-192 Brachytherapy Skin Applicator
Using Monte Carlo-Based Dosimetry.
AB - PURPOSE: AccuBoost(r) applicators are designed to deliver boost dose after whole
breast irradiation in substitution for electron boost. By augmenting the current
design through adding a wedge inside the applicator and atungsten window above
the skin surface, the AccuBoost applicators can be used to treat skin cancer.
This study aimed to design a skin applicator that could deliver brachytherapy in
a conformai and homogeneous manner to the skin while minimizing OAR dose.
METHODS: The 6 cm round AccuBoost applicator served as the foundation for
variations of an internal cone, internal wedge, and external window. Monte Carlo
(MC) methods (MCNP5)were used for dose characterization and design optimization
of these tungsten-alloy components. Specifically, the cone, wedge, and window
dimensions were iteratively varied in MC simulations based on HDR Ir-192 dose
distributions having (0.5 mm)2 voxels in a soft tissue phantom. The design goal
was an applicator that can protect tissue > 5 mm while providing lateral dose
conformity and a homogeneous dose distribution for tissue < 3 mm. RESULTS: The
internal wedge angle governed field size to be irradiated, limiting depth-dose
spread into the phantom. Dose conformity was enhanced by the internal cone and
collimating window. Window thickness increased required treatment time, where 3
mm was determined to be optimal when considering tradeoff between depth dose and
dose rate. With a lesion thickness of 3 mm and setup uncertainty of 1 mm, the
optimal design provided better lateral coverage at d = 5mm. Here, the dose was
less than 30% of that within the treatment aperture. CONCLUSION: Standardized
criteria were established for dose optimization of a skin applicator. Using these
criteria and MC methods, an optimized design was obtained. Optimization is
underway for other applicator diameters. Clinical evaluation within a 3D
treatment planning system and comparison with other brachytherapy skin
applicators is ongoing. Prof. Rivard is a stakeholder of Advanced Radiation
Therapy, LLC.
PMID- 28517380
TI - SU-D-218-05: Material Quantification in Spectral X-Ray Imaging: Optimization and
Validation.
AB - PURPOSE: To develop and validate a multivariate statistical method to optimize
scanning parameters for material quantification in spectral x-rayimaging.
METHODS: An optimization metric was constructed by extensively sampling the
thickness space for the expected number of counts for m (two or three) materials.
This resulted in an m-dimensional confidence region ofmaterial quantities, e.g.
thicknesses. Minimization of the ellipsoidal confidence region leads to the
optimization of energy bins. For the given spectrum, the minimum counts required
for effective material separation can be determined by predicting the signal-to
noise ratio (SNR) of the quantification. A Monte Carlo (MC) simulation framework
using BEAM was developed to validate the metric. Projection data of the m
materials was generated and material decomposition was performed for combinations
of iodine, calcium and water by minimizing the z-score between the expected
spectrum and binned measurements. The mean square error (MSE) and variance were
calculated to measure the accuracy and precision of this approach, respectively.
The minimum MSE corresponds to the optimal energy bins in the BEAM simulations.
In the optimization metric, this is equivalent to the smallest confidence region.
The SNR of the simulated images was also compared to the predictions from the
metric. RESULTS: TheMSE was dominated by the variance for the given material
combinations,which demonstrates accurate material quantifications. The
BEAMsimulations revealed that the optimization of energy bins was accurate to
within 1keV. The SNRs predicted by the optimization metric yielded satisfactory
agreement but were expectedly higher for the BEAM simulations due to the
inclusion of scattered radiation. CONCLUSIONS: The validation showed that the
multivariate statistical method provides accurate material quantification,
correct location of optimal energy bins and adequateprediction of image SNR. The
BEAM code system is suitable for generating spectral x- ray imaging simulations.
PMID- 28517381
TI - SU-D-BRB-02: Investigations of Secondary Ion Distributions in Carbon Ion Therapy
Using the Timepix Detector.
AB - PURPOSE: Due to the high conformity of carbon ion therapy, unpredictable changes
in the patient's geometry or deviations from the planned beam properties can
result in changes of the dose distribution. PET has been used successfully to
monitor the actual dose distribution in the patient. However, it suffers from
biological washout processes and low detection efficiency. The purpose of this
contribution is to investigate the potential of beam monitoring by detection of
prompt secondary ions emerging from a homogeneous phantom, simulating a patient's
head. METHODS: Measurements were performed at the Heidelberg Ion-Beam Therapy
Center (Germany) using a carbon ion pencil beam irradiated on a cylindrical PMMA
phantom (16cm diameter). For registration of the secondary ions, the Timepix
detector was used. This pixelated silicon detector allows position-resolved
measurements of individual ions (256*256 pixels, 55MUm pitch). To track the
secondary ions we used several parallel detectors (3D voxel detector). RESULTS:
For monitoring of the beam in the phantom, we analyzed the directional
distribution of the registered ions. This distribution shows a clear dependence
on the initial beam energy, width and position. Detectable were range differences
of 1.7mm, as well as vertical and horizontal shifts of the beam position by 1mm.
To estimate the clinical potential of this method, we measured the yield of
secondary ions emerging from the phantom for a beam energy of 226MeV/u. The
differential distribution of secondary ions as a function of the angle from the
beam axis for angles between 0 and 90 degrees will be presented. In this setup
the total yield in the forward hemisphere was found to be in the order of 10-1
secondary ions per primary carbon ion. CONCLUSIONS: The presented measurements
show that tracking of secondary ions provides a promising method for non-invasive
monitoring of ion beam parameters for clinical relevant carbon ion fluences.
Research with the pixel detectors was carried out in frame of the Medipix
Collaboration.
PMID- 28517382
TI - SU-D-213CD-01: 4D Ultrasound Calibration for Radiotherapy Guidance Using
Automatic Intramodality Image Registration.
AB - PURPOSE: In prior work we developed a robotic system providing real-time soft
tissue ultrasound (US) volumes during radiotherapy beam delivery. for image
guidance, the US volumes must be transformed to the linear accelerator reference
frame. In this work we propose and characterize a new method of calibrating 4D US
volumes based on automatic intramodality image registration. METHODS: A dynamic
navigation link was used to port 3D US volumes from a Philips iU22 xMatrix
machine to a PC in real-time. Sixty volumetric (3D) US images of a pelvic phantom
were collected from various probe positions while the transducer's pose was
monitored by an optical tracking system. US volumes were automatically registered
to the first US volume using normalized mutual information. A system of equations
was formulated and solved for the US probe-to-image transformation using the
registration transformations and the optical tracking information. Accuracy of
the US calibration was assessed on eight additional US volumes with two separate
methods. In the first method, a set of three fiducial markers implanted in the
phantom was manually selected in each volume by three individual readers.
Selected marker locations were reconstructed in the stationary camera frame, and
for each marker, mean distance to the reconstructed centroid was measured. In the
second method, a bladder structure was semi-automatically segmented in each image
volume. Mean distance between bladders segmented in a reference volume and the
other seven volumes was computed. Calibration accuracy was also investigated as a
function of the number of calibration images used. RESULTS: Mean error for the
fiducial marker reconstruction was 2.3 mm. Mean distance error between segmented
structures was 1.1 mm. The proposed calibration method typically converged with
less than 20 images. CONCLUSION: Automatic image registration facilitates fast
and simple US spatial calibration with accuracy under 2.3 mm using any US
phantom. This work is supported in part by the Stanford University BioX program
and by Philips Medical. Two of the authors of the abstract are employed by
Philips Medical.
PMID- 28517383
TI - SU-D-211-02: A Framework for 4pi Radiotherapy.
AB - PURPOSE: Inclusion of highly non-coplanar treatment angles increases radiations
dose conformality and critical organ sparing. However, implementation of this
treatment strategy has been hampered by inaccurate solution space modeling,
limited automated beam selection methods, the lack of efficient beam sequencing
program and integrated collision prevention. The aim is to develop a 4pi
radiotherapy paradigm that takes full advantage of modern computer-controlled
robotic C-arm linear accelerators. METHODS: The beam geometry solution space was
modeled by 3D surface scanning of the couch, gantry and patient. In order to
utilize the entire solution space and optimize MLC resolution, variable source-to
tumor distances were introduced. Conformai radiation doses were computed using
convolution/superposition from uniformly distributed solid angles. Beam
orientation optimization was performed using a column generation and pricing
approach, which was also used to optimize beam fluence intensity modulation. A
level set method was then employed to automatically sequence beams so the
treatment time and couch motion can be minimized while avoiding collision on the
path. RESULTS: The machine and patient surface was accurately measured and a
cocoon shaped solution space was created with an integrated gap buffer of 4 cm.
14 conformai beams were typically selected to maximize target dose coverage and
minimize critical organ doses. Compared with manual non-coplanar and coplanar
volumetric modulated arc therapy plans, an average 20% improvement was observed
in high dose spillage, defined as the 50% isodose volume divided by the target
volume, in a wide range of clinical cases including brain, lung, liver and
partial breast cancer. CONCLUSIONS: We have established a framework that
overcomes major technical difficulties associated with automated planning and
delivery of highly non-coplanar treatment on the widely available C-arm linacs.
Compared with coplanar volumetric modulated arc therapy plans, 4pi plans improve
nearly all aspects of the dosimetry while remain highly deliverable.
PMID- 28517384
TI - SU-D-217BCD-05: Analytic Determination of Size of Water Cylinder Absorbing Equal
Radiation Dose as a System of Concentric Cylinders of Arbitrary Composition:
Application for Pediatric CT.
AB - PURPOSE: To develop analytic formulae for calculating absorbed dose to a system
of concentric cylinders and to use this to determine the size of water cylinder
which would absorb the same dose in a matching field. Appropriate scaling of
radiation output to patient size is of particular interest in pediatric CT
(TG204). METHODS: For a given CT scanner output, absorbed dose increases as
patient size decreases. Analytic functions can calculate the dose delivered to
systems of concentric cylinders of varying size and composition. In particular
these functions provide useful insight when considering examinations in body
regions with large variations in attenuation, such as the chest (which can be
modeled as concentric cylinders of heart, lung, rib and soft tissue). Iterative
calculations rapidly determine the size water cylinder required to absorb the
same dose in matching radiation fields. More general findings put limits on some
of the methods for determining size specific dose estimates (SSDE). RESULTS: For
the simple chest model, in the absence of scatter or bow tie filter
considerations, the equivalent water phantom would have a diameter of just over
half the chest equivalent concentric cylinder phantom. A more general Result is
that in the limit of very small size, the absorbed dose in a fixed irradiating
field depends only on mass attenuation coefficient. CONCLUSIONS: The concentric
cylinder model developed can be used to study the scaling of radiation dose with
patient size. In particular, the water phantom absorbing the same dose as the
chest region has only about half the diameter. An important conclusion is that in
the limit of small size, absorbed dose depends on mass attenuation coefficient
only and that in this limit an equivalent water phantom does not exist.
PMID- 28517386
TI - SU-D-BRB-06: Comprehensive Population-Averaged Arterial Input Function (AIF) for
DCE-MRI of Head and Neck Cancer.
AB - PURPOSE: To generate a composite population-averaged(PA)-AIF for quantitative
analysis of DCE-MRI data in head and neck (H&N) patients that is based on the
right (RT) and left (LT) carotids, two pre-treatment scans, and one post
treatment scan. METHODS: Twenty patients were imaged while undergoing concurrent
chemoradiation (CRT) for H&N malignancies. The imaging protocol (1) included two
baseline scans one week apart (Base1, Base2), and one scan 1 week post-CRT
(Post). For each patient and time point, regions of interest (ROIs) in both the
RT and LT carotids were drawn on coronal images. The plasma concentration curves
of all ROIs were averaged and fit to a bi-exponential decay function to obtain
the final PA- AIF (AvgAll). The ROIs were also divided by time point to obtain
AvgBasel, AvgBase2, and AvgPost AIFs. The vascular transfer constant for both
primary and nodes, Ktrans , was calculated (iCAD, Inc.) using the 4 AIFs, as well
as the generic Weinmann's AIF. The median Ktrans values resulting from the AvgAll
AIF were compared using Bland-Altman plots with the ones obtained from each
individual time point. The Wilcoxon signed-rank test was used to compare the
proposed AvgAll AIF and the generic AIF. RESULTS: The plasma parameters for the
AvgAll AIF were a1,2=27.1135/17.6486 kg/liter, m 1,2=11.7525/0.2054 min-1 . The
differences in Ktrans values using these coefficients vs. Weinmann's were
statistically significant (p<0.0001). The median Ktrans values from the
AvgBasel,AvgBase2, and AvgPost AIFs were, in most cases, not significantly
different from the AvgAll values, indicating that the latter is appropriate
foruse at all time points. CONCLUSIONS: A population-averaged AIF for H&N was
generated that accounts for differences in RT vs. LT carotids, day-today AIF
fluctuations, and treatment-induced AIF changes. It is not necessary to measure a
post-treatment AIF to evaluate treatment-induced Ktrans changes.l. Craciunescu et
al., MedPhys, 37, 6, 2683, 2010.
PMID- 28517385
TI - SU-D-BRCD-01: Evaluation of Zebra Multi-Layer Ionization Chamber System for
Patient Treatment Field and Machine QA for Spot Scanning and Passive Scattering
Proton Beams.
AB - PURPOSE: To evaluate Zebra multi-layer ionization chamber system for patient
treatment field and machine QA for spot scanning proton beams (SSPB) and passive
scattering proton beams (PSPB). METHODS: Zebra dose measurement system (IBA
Dosimetry), consisting of 180 parallel platechambers with 2 mm detector spacing,
was used for measuring proton beamdepth dose curves (DDC) for spread out Bragg
peaks (SOBP) and single spot pristine Bragg peaks (PBP). The measurements were
performed for 100 to 250 MeV PSPB and 89.2 to 221.8 MeV SSPB using the Hitachi
ProBeat synchrotron based delivery system. An in-house Matlab based analysis
software was used to compare the Zebra measured DDC with those measured by the
Markus chamber in a PTW water tank (MC-WT). Several verification plans in the
water phantom were created for patient treatment fields using the Eclipse
treatment planning system (TPS). The DDC for individual verification fields were
measured using the Zebra andcomparisons were made with the TPS calculations.
RESULTS: The dosedifferences between the Zebra and MC-WT measurements in the
plateau regions of the DDC are within 2% for various energies of PSPB, but are
larger than 2% at the sharp dose distal gradient regions. The values for distal
penumbra widths, range and SOBP widths from Zebra and MC-WT measurements agree
within 0.5 mm, 1.5 mm, and 2 mm, respectively. The Zebra measured values of the
range of the single spots also agreed within 1 mm with their established values
from other measurements. The Zebra measured DDC of verification plan of patient
treatment fields showed goodagreement with those from the TPS. CONCLUSIONS: Our
investigation shows that Zebra can be useful for fast and reasonably accurate
measurements of the DDC of pristine and spread-out Bragg peaks of both spot
scanning and passive scattering proton beams.
PMID- 28517387
TI - SU-D-213CD-04: Dosimetric Evaluation of HexaPOD as a Tool for Patient Setup
Verification Accuracy.
AB - PURPOSE: To quantify the dosimetric accuracy of 6 degrees vs. 3 degrees of motion
for patient positioning for cone-beam CT and HexaPOD Evo RT system (Elekta, Inc.)
using the ArcCHECK (Sun Nuclear Corporation, software v.6.0) QA phantom. METHODS:
The average absolute values of our daily reported patient hexapod shift data were
recorded and averaged for 18 patients. Using the CT scans of ArcCHECK, a QA plan
was created in the Pinnacle (v.9.0) treatment planning system. By setting up
ArcCHECK according to the QA plan and measuring the dose on Elekta Synergy, the
baseline data was established. Next, an artificial shift was introduced in our
phantom setup. A cone-beam CT scan of the phantom was obtained and images
adjusted. The resulting translational and rotational shifts were recorded. The
table was then moved according to the translational shifts only, and another
measurement was taken. Next, using hexapod translational and rotational shifts,
the table was moved in 6 degrees of motion, and the dose was re-measured.
RESULTS: For 18 IMRT patients, the average translational shifts were: x= 0.53 cm,
y=0.38 cm and z= 0.516 cm, and average rotational shifts were pitch=0.979 degrees
, roll=0.8 degrees and yaw= 0.67 degrees . The ArcCHECK phantom measured results
were quantified using 3%, 3mm distance to agreement gamma analysis criteria when
comparing measured to planned dose. Our measurements showed that an average 97.3%
of the points agreed in plans with no shift. After the artificial shift was
introduced, and cone-beam CT translational shifts were applied, 76.3% of points
agreed. When both rotational and translational shifts were applied using Hexapod,
an average of 93.4% of points agreed. CONCLUSIONS: Using hexapod for imaging and
patient positioning results in a significantly more accurate dose delivery as
compared to using only CBCT, as shown by our ArcCHECK QA phantom results.
PMID- 28517388
TI - SU-E-E-01: Commissiong of Linear Accelerator and Beam Modeling in Treatment
Planning Systems.
AB - PURPOSE: Sooner or later every medical physicist is involved with commissioning
and beam modeling of a new linear accelerator (linac) and a new treatment
planning system (TPS). In spite of all instructions and training offered by the
vendors, at the time a new linac is being purchased and added to the present ones
the outside help is not so complete. The physicist who has to perform the
commissioning job may not even be the one who was trained for that. What we are
missing is a good comprehensive set of information and instructions on how to
do's. From shielding calculation verifications, surveys, to collecting the beam
data, modeling, entering the data into the TPS, and verifications of the goodness
of the data we need a lot of support and we don't have it. I will provide a step
by step description of the required work with the results we are looking for.
METHODS: Presentation of the shielding calculations, survey required, tools
needed to perform them. Detailed beam data collections, scanning system needed,
machine set of specs needed, applicator details needed. Importing beam data from
the scanning system and beam calculations. Algorithms used in dose calculation,
IMRT optimization, heterogeneity corrections presented to be understood before
modeling the beam data. RESULTS: At the completion of this course the medical
physicist will be able to commission a linear accelerator and a treatment
planning system with confidence and very little help from the outside.
CONCLUSIONS: This compendium of detailed instructions on commissioning a linear
accelerator will provide good uidance to every physicist who will be involved
with the installation and bringing into safe use for treatment of a new linear
accelerator.
PMID- 28517389
TI - SU-D-217A-06: Impact of Anterior-Posterior (AP) and Posterior-Anterior (PA) Scout
Scans on the CT Radiation Dose in the Whole Body PET/CT Scan.
AB - PURPOSE: CT can contribute over 50% of radiation dose in the whole body (WB)
PET/CT scan. Tube current modulation (TCM) is a standard technique for reducing
CT radiation dose to the patient by changing the tube current with the patient
size, and is controlled by a very low-dose scoutscan, which assumes the patient
is positioned at the center of the CT gantry opening. However, most patients are
not positioned at the center due to practicality or to avoid claustrophobic or to
reduce time of radiation exposure from the patient to the technologist. We study
the impact of the AP and PA scout scans to the patient radiation exposure from
CT. METHODS: Ina retrospective study of 200 patients, each received two WB PET/CT
scans: one with AP, and the other one with PA. The helical CT with TCM and PET
acquisitions were identical in both scans. Separation of the two scans was about
10 months in average. The scans were performed on four GE PET/CT scanners: three
16- and one 64-slice with the same TCM settings. The 200patients were selected
for the same scan coverage and similar body weight (difference = 3 kg). The tube
current in each slice and average exposure tothe patient were recorded and
compared. RESULTS: The AP scout caused lower radiation dose on 94% of the
patients. Both the tube current, and radiation exposure were reduced by 46+/-30
mA and 1.6+/-1.0 mGy, respectively. The effective radiation dose is reduced by
1.7+/-1.2 mSv. These results were statistically significant (p<0.00001).
CONCLUSIONS: The AP scout caused significantly less radiation dose than the PA
scout in the CT scan of the whole-body PET/CT scan. Care should be taken to
select theorientation of the scout scan to achieve appropriate radiation exposure
to the patient when TCM is applied.
PMID- 28517390
TI - SU-D-BRA-02: An Extended Time-Variant Seasonal Autoregressive Model-Based
Prediction for Irregular Breathing Motion Tracking.
AB - PURPOSE: Real-time tumor position/shape measurement and dynamic beam tracking
techniques allow accurate and continuous irradiation to moving tumor, but there
can be a delay of several hundred milliseconds between observation and
irradiation. A time-variant seasonal autoregressive (TVSAR) model has been
proposed for compensating the delay by predicting respiratory tumor motion with
sub-millimeter accuracy for a second latency. This is the-state-of-the-art model
for almost regular breathing prediction so far. In this study, we propose an
extended prediction method based on TVSAR to be usable for various breathing
patterns, by predicting the residual component obtained from conventional TVSAR.
METHODS: An essential core of the method is to take into account the residual
component that is not predictable by only TVSAR. The residual component involves
baseline shift, amplitude variation, and so on. In this study, the time series of
the residual obtained for every new sample are predicted by using autoregressive
(AR) model. The order and parameters of the AR model is adaptively determined for
each residual component by using an information criterion. Eleven data sets of 3
D lung tumor motion, observed at Georgetown University Hospital by using
Cyberknife Synchrony system, were used for evaluation of the prediction
performance. RESULTS: Experimental results indicated that the proposed method is
superior to those of conventional and the state-of-the-art methods for 0 to 1 s
ahead prediction. The average prediction error of the proposed method was 0.920
plus/minus 0.348 mm for 0.5 s forward prediction. CONCLUSION: We have developed
the new prediction method based on TVSAR model with adaptive residual prediction.
The new method can predict various respiratory motions including not only regular
but also a variety of irregular breathing patterns and thus can compensate the
bad effect of the delay in dynamic irradiation system for moving tumor tracking.
A part of this work has been financially supported by Varian Medical Systems
Inc., Palo Alto, CA and Japan Society for the Promotion of Science (JSPS), Japan.
PMID- 28517391
TI - SU-D-213CD-06: Workflow and Safety Systems of a Linac-MR Sim-Brachytherapy
MRgRTTM Facility.
AB - PURPOSE: To develop the operational workflow and safety systems of a magnetic
resonance-guided radiotherapy system (MRgRTTM), which comprises an MR scanner on
rails that travels between a linac vault, MR simulation room and brachytherapy
suite. METHODS: To develop a safe and streamlined clinical workflow, we conducted
a comprehensive process review based on a layered approach to overall MRgRT
safety that included i) facility design, (ii) workflow iii) system design and
interlocks and iv) policies and procedures. We applied existing guidelines for MR
and radiation safety, and employed system-level failure modes and effects
analyses to design the MRgRT facility and clinical procedures. RESULTS: In the
MRgRT system configuration, the MR and treatment systems are physically decoupled
and used independently requiring novel administration of existing MR and
radiation guidelines. A key element for the safe operation of the moving MR unit
is the concept that all three rooms represent zone 4 areas (American College of
Radiology guidelines). Using this concept, we applied MR guidelines to develop
safe procedures for the overall suite, including screening of all persons
entering the suite in zone 2 and control of ferromagnetic materials. We generated
a clinical workflow that ensures expedient and safe transition between MR imaging
and treatment delivery in both the linac and brachytherapy rooms. In addition, we
designed emergency protocols for MRgRT, which helped drive requirements for the
facility and system design, e.g., need for an accessible MR-safe stretcher.
CONCLUSIONS: We designed the first comprehensive description of the MRgRT
workflow, interlocking systems and safety procedures. With this layered approach
to safety, we addressed critical aspects regarding safe operation and workflow
for the system and provided multiple redundancies for key processes. Coupled with
customized staff training, the proposed design ensures the safe operation of the
MRgRT facility. This work has received research personnel support from IMRIS.
PMID- 28517392
TI - SU-D-213AB-02: Optimal Design of Multichannel Vaginal Cylinder Applicators for
High Dose Rate Brachytherapy.
AB - PURPOSE: To determine the optimal location of catheters in multichannel vaginal
applicators to appropriately cover the vaginal cuff target and minimize dose to
the organs at risk (OARs) and hot spots in the target. METHODS: A new
multichannel vaginal applicator with a diameter of 30 mmconsists of a single
central catheter and an outer array of eight catheters. A total of 20 plans were
generated from 5 patients by using different outer catheter locations at r = 4,
8, and 12 mm. The target was defined as a 5 mmcircumferential shell extending 4
cm in length around the applicator, excluding the bladder, rectum, and bowel. An
inverse planning simulated annealing algorithm and graphical optimization was
applied to ensure the prescription dose (7.0 Gy per fraction) covered >97% of the
target and minimized dose to the OARs. Target coverage (D90 and V100), hot spots
(V150 and V200), and OAR doses (D0.1cc, D1cc, and D2cc) from the various catheter
placements were compared to single catheter plans. RESULTS: By study design all
plans had the same target coverage D90 (105.0- 108.3%) and V100 (97.1-97.2%). The
V150 and V200 were 16.1% and 3.4% (r=0mm), 17.3% and 4.2% (r=4mm), 20.1% and 2.2%
(r=8mm), and 30.1% and 6.0% (r=12mm). The DO.1cc to the OARs from the various
catheter placements at r = 4, 8, and 12 mm was reduced by 4.0%, 8.6%, 11.9%
(bladder), 7.4%, 13.2%, and 17.4% (rectum), when compared to the central catheter
plans. CONCLUSIONS: Multichannel vaginal applicators provide better dosimetry
than single channel applicator. The catheter array located closest to the
applicator surface most significantly reduces dose tothe OARs at the expense of
larger hot spots in the target. The array in the middle of the applicator radius
provides significantly decreased dose to the OARs and gave relatively smaller hot
spots.
PMID- 28517393
TI - SU-D-218-04: Evaluation of the Performance of the Solid State X-Ray Image
Intensifier (SSXII) Using Generalized Metrics.
AB - PURPOSE: To evaluate the performance of the Solid State X-ray Image Intensifier
(SSXII) using generalized linear-system metrics and to study the effect of
different scatter fractions, object magnifications, and focal spots onits
performance. METHODS: The SSXII is a high-resolution and high- sensitivity region
of-interest x-ray imaging detector that provides real-timeimaging with low
instrumentation noise. To evaluate the total system performance for a clinical
environment, we used generalized metrics that include the effects of scattered
radiation, finite focal-spot size, and geometric unsharpness. For comparison, a
commercial standard flat-panel detector (FPD) was used. The focal-spot MTF was
obtained by taking theFourier Transform of the point-spread function of x-ray pin
hole images. The detector MTF was measured using the standard edge method. The
scatter MTF was simulated with a theoretical model. We have calculated the GMTF
and GDQE for the SSXII and FPD. Three focal-spots (small, medium, and large),
different object magnifications and scatter fractions were used for the GMTF and
GDQE comparison. RESULTS: The GMTF andthe GDQE were shown to be degraded
significantly from that of the detectoralone at the higher spatial frequencies
because of blur due to the finite sizeof the focal-spot, and at the lower
frequencies because of scatter. Furthermore, the degradation increases even more
as the focal-spot size,object magnification and scatter fraction increases. The
GMTF and the GDQE for the FPD were similar to those of the SSXII at lower
frequencies, but were limited to frequencies below its 2.5 cycles/mm Nyquist
frequency due to the 194-micron pixel size compared to the 18.9 cycles/mm Nyquist
frequency of the 26.4-micron pixel-size SSXII. CONCLUSIONS: This work
demonstrates that the SSXII and the FPD have similar performance at thelower
spatial frequencies, whereas, the SSXII demonstrates superior performance over
the FPD at higher frequencies. Supported in part by: NIH Grants R01-EB008425, R01
EB002873 and an equipment grant from Toshiba Medical Systems Corp.
PMID- 28517394
TI - SU-D-BRB-01: 4D-CT Lung Ventilation Images Vary with 4D-CT Sorting Techniques.
AB - PURPOSE: 4D-CT ventilation imaging is a novel promising technique for lung
functional imaging and has potential as a biomarker for radiation pneumonitis,
but has not been validated in human subjects. The current 4D- CT technique with
phase-based sorting results in artifacts at an alarmingly high frequency (90%),
which may introduce variations into ventilation calculations. The purpose of this
study was to quantify the variability of 4D- CT ventilation imaging to 4D-CT
sorting techniques. METHODS: Two 4D-CT images were generated from the same data
set by: (1) phase-based; (2) anatomic similarity- and abdominal displacement
based sorting for five patients. Two ventilation image sets (V_phase and V_anat)
were then calculated by deformable image registration of peak-exhale and peak
inhale4D-CT images and quantification of regional volume change based on
Hounsfield unit change. The variability of 4D-CT ventilation imaging
wasquantified using the voxel-based Spearman rank correlation coefficients and
Dice similarity coefficients (DSC) for the spatial overlap of segmented low-
functional lung regions. The relationship between the abdominal motionrange
variation and ventilation variation was also assessed using linearregression.
Furthermore, the correlations between V_phase or V_anat and SPECT ventilation
images (assumed ground-truth) were compared. RESULTS: In general, displacement-
and anatomic similarity-based sorting reduced 4D- CT artifacts compared to phase
based sorting. The voxel-based correlationsbetween V_phase and V_anat were only
moderate (range, 0.57-0.77). The DSCs for the low-functional lung regions were
moderate to substantial (0.58-0.70). The relationship between the motion range
variation and ventilation variation was strong on average (R2=0.79+/-0.25),
suggesting that ventilation variations are related to 4D-CT artifacts. Vanat was
found to improve correlations with SPECT ventilation images compared to V_phase.
CONCLUSIONS: 4D-CT ventilation images vary markedly with 4D-CT sorting
techniques. 4D-CT artifacts should be considered as a significant source of
variation in 4D-CT ventilation imaging during its validation. This study
wassupported in part by NIH/NCI R01 93626. SK and CL are employees ofPhilips
Research.
PMID- 28517395
TI - SU-D-BRA-06: Investigation of Prostate Intrafractional Motion during External
Beam Radiotherapy for a Large Patient Population.
AB - PURPOSE: To analyze and report prostate intrafractional motion recorded online
during external beam radiotherapy and to provide guidance for advanced prostate
IMRT. METHODS: Prostate intrafractional motion during IMRT and RapidARC
treatments was tracked and recorded using a Calypso 4D-localization system. Data
for 8600 treatment fractions of 230 prostate patients was analyzed. The
percentage of treatment fractions, the fractional treatment time, and the
fractional time of any individual minute were analyzed separately for prostate
movements greater than the thresholds (2, 3, 5 and 7mm). RESULTS: The percentages
of fractions in which prostate shifted more than the thresholds for a duration
>10 seconds are 66.2%, 34.9%, 8.9% and 2.6% (57.9%, 27.9%, 5.2% and 0.8% for >30
seconds duration), respectively. For 10 patients who exhibited the largest
motion, the percentages are 95.2%, 76.0%, 43.2% and 14.7% (91.3%, 72.4%, 36.3%
and 6.0% for >30 seconds duration). The fractional time for motion larger than
the thresholds is 27.8%, 10.7%, 1.6% and 0.3% (56.2%, 33.7%, 11.2% and 2.1% for
these patients). The posterior-direction motion is significantly higher than
those in other directions. The fractional time of an individual minute with shift
>3mm is higher at the 10th minute than at the 5th minute (20% vs. 10%) after the
initial setup. For treatments completed within 5 minutes, the average fractional
time with motion >3mm was lower than those within 10 minutes (4% vs. 12%).
Irregular movements were observed most likely in the first minute after patient's
setup, which were 12% and 7% among all fractions with movements >2mm and >3mm,
respectively. CONCLUSIONS: The prostate intrafractional motion was within 3mm for
most treatment fractions. However, larger movements were observed for some
patients, who require real-time corrections or larger treatment margins. The
results indicate that it is beneficial if the treatment can be completed within 5
minutes.
PMID- 28517396
TI - SU-D-211-01: Effect of Immobilization/support Devices and Air Gap on Skin Doses
for Stereotactic Body Radiotherapy with Abdominal Compression Device.
AB - : Purpose To evaluate the effects of the couch, the immobilization/support
devices, and air gap on the skin dose for SBRT treatment with abdominal
compression device and to investigate strategies to minimize skin dose by phantom
measurementMaterial and methodsSkin-sparing comes from lower dose in buildup
region, anything added between tissue and air may change buildup PDD curve hence
skin dose increases. To investigate such effects due to different buildup
materials and air gap between the buildup material and the surface, we employed
EBT2 film in slab and water phantoms to measure doses at depths varying from
surface to dmax, field sizes (4*4 to 10*10 cm2 ), and air gaps from 5 to 15 cm
for 6 MV photons. Measured dose was normalized to dose at dmax for a 10*10 cm2
field. The buildup materials included table tops (tennis net, Exact Couch and
Indexed Immobilization table tops), vacuum bags (Civco Vac-Lok and Med-Tec
cushions), and body frames (Elekta stereotactic body frame and Civco Body Pro
Loc). ResultsThe relative doses at depth of 1.00 mm were 0.63 with no buildup,
0.90 with couch+6cm bag, 0.91 with bodyframe+bag, and 0.96 with
couch+bodyframe+bag for a 4*4 cm2 field. With a 10*10 cm2 field, the above values
changed to 0.67, 0.94, 1.01, and 0.97, respectively. Thick bag (6.0cm) increased
skin dose by 10% comparing to the thinner bag (1.5cm). For a buildup (couch +
body frame) plus air gap, the relative doses were 0.73, 0.84, and 0.91 for air
gap of 15.0, 10.0, and 5.0 cm, respectively, for a 10*10 cm2 field. CONCLUSIONS:
The skin dose increases by up to 40% if patient was treated through the
immobilization device or couch. Skin dose also increased with increasing field
size. Introduction of large air gap may recover much of the lost buildup effect.
PMID- 28517397
TI - SU-D-217BCD-04: How Do We Know How Low Can We Go in Lung Cancer Screening CT?
AB - PURPOSE: To demonstrate a technique for determining the acceptable radiation dose
level for lung cancer screening CT. METHODS: 20 patients who underwent a
clinically indicated routine chest CT scan with 120 kV and 180 quality reference
mAs were enrolled in this IRB approved study. Automatic exposure control was used
to adjust for patient size. Scanner output, as expressed in CTDIvol, varied
accordingly (mean=16.8 mGy, range=7.6 to 26.6 mGy). A previously validated noise
insertion software tool developed in our lab was used to simulate scans acquired
with reduced dose levels (12.5%, 25%, 50% of the original dose level). Images
reconstructed from the same raw data but at the original and simulated, reduced
dose levels were randomized and blindly reviewed by three thoracic radiologists.
Lung and soft tissue regions were graded for two different imaging tasks: 1)
routine diagnostic CT exam of the chest and 2) screening exam of the chest for
lung cancer. A 5 point scale was used to rate each exam for each task (1=too
noisy, significantly impacted confidence to 5=excellent quality, excellent
confidence). Exams were considered acceptable when at least two of the three
radiologists gave a score of 3 or higher. The percentage of patients meeting this
definition of acceptable was calculated for each imaging task, dose level, and
tissue type (lung or soft tissue). RESULTS: The percentages of exams considered
acceptable for the purpose of lung cancer screening were 90%, 100%, 100%, 100%
(lung tissue) and 85%, 100%, 100%, 100% (soft tissue) at 12.5%, 25%, 50% and 100%
of original dose level. For the purpose of routine diagnostic chest CT, the
percentage of acceptable exams were 75%, 95%, 100%, 100% (lung tissue) and 35%,
85%, 90%, 100% (soft tissue) at 12.5%, 25%, 50% and 100% of original dose level.
CONCLUSIONS: At 25% of the dose used for routine diagnostic chest CT at our
institution, acceptable image quality for the purpose of CT screening for lung
cancer was achieved in 100% of the evaluated cases. This factor of 4 in dose
reduction relative to routine chest exams is similar to what was used in the NLST
trial.
PMID- 28517398
TI - SU-D-213AB-06: Surface Texture and Insertion Speed Effect on Needle Friction.
AB - PURPOSE: High frictional forces between the needle surface and tissue cause
tissue deflection which hinders accurate needle placement for procedures such as
brachytherapy and needle biopsy. Accurate needle placement isimportant to
maximize procedure efficacy. This work investigates how needle surface roughness
and insertion speed affect the frictional forcebetween a needle and tissue.
METHODS: A friction experiment was conducted to measure the force of friction
between bovine liver and three 11 gauge needles having Ra surface roughness of
3.43, 1.33, and 0.2 MUm. Each of the three needles were mounted on a linear slide
and were advanced and retracted through bovine liver at speeds of 50, 100, 150,
and 200 mm/s for a total of 12 trials. In each trial the needle was advanced and
retracted in 10 cycles producing a steady state insertion force and a steady
state retraction force for each cycle. A force sensor connecting the needle to
the linear slide recorded the resistance force of the needle sliding through the
liver. The liver was mounted in a box with a pneumatic cylinder which compressed
the liver sample by 11.65 kPa. RESULTS: The roughest needle (Ra = 3.43 MUm) on
average produced 68, 73, 74, and 73% lower friction force than the smoothest
needle (Ra = 0.2 MUm) for the speeds of 50, 100, 150, and 200mm/s, respectively.
The second roughest needle (Ra = 1.33 MUm) on average produced 25, 45, 60 and 64%
lower friction force than the smoothest needle (Ra = 0.2 MUm) for the speeds of
50, 100, 150, and 200 mm/s, respectively. CONCLUSIONS: Rougher needle surface
texture and higher insertion speed reduced frictional forces between the tissue
and the needle. Future studies will examine how frictional forces can be modeled
and predicted given surface texture and insertion speed.
PMID- 28517399
TI - SU-D-BRB-05: Small Animal Lung Compliance Imaging: Assessment System for Tissue
Sensitivity to Radiation Induced Lung Injury.
AB - PURPOSE: Recent clinical trials and animal studies have indicated that the tissue
sensitivity to radiation induced lung injury (RILI) may be region- specific. In
this study, we propose a new 4D cone beam CT (CBCT) basedcompliance imaging
method to measure regional pulmonary function change in precisely irradiated
small animal under CBCT guidance on small animal radiation research platform
(SARRP) to facilitate our understanding of region-specific tissue sensitivity to
RILI. METHODS: Four Sprague-Dawley rats underwent prospective pressure gated 4D
CBCT on SARRP. Three animals were selected as control group which underwent a
second 4D CBCT scan. The fourth animal was irradiated in the central lung (24 Gy)
using 3 * 3 mm collimating cone 2 months prior to the scan. The specific
compliance (Csp) was calculated via the real time pressure measurement from the
ventilator and displacement field from 3D B-spline image registration between the
end of inhale and end of exhale phases from the 4D CBCT scan. The 3D Csp maps
from the control animal group were mapped to the irradiated animal as a Csp
functional atlas for statistical analysis. We alsoevaluated the repeatability of
the Csp measurement on a voxel-by-voxel basis. RESULTS: No significant Csp
difference is found after two month of radiation between the irradiated rat
(0.22+/-0.05) and the functional atlas (0.21+/-0.07). The observation is
consistent with previous publications. The averaged linear correlation
coefficient between the voxel-by-voxel Csp measurements from initial and repeat
scans in control group is 0.98. CONCLUSIONS: We proposed a method that uses 4D
CBCT based compliance imaging to measure region-specific tissue sensitivity of
RILI. We compared the irradiated animal two months after radiation with the
control group. Our study shows an excellent robustness of the proposed method for
regional lung tissue specific compliance measurement. This work was supported in
part by UVa George Amorino Pilot Grant.
PMID- 28517400
TI - SU-D-213CD-03: Live Video-Guided Volumetric Tracking of Respiration Motion.
AB - PURPOSE: To introduce video surface imaging guidance in synchronization with 4D
cone-beam CT (CBCT) scans, and in combination with respiration- gated or target
tracked dose delivery to treat mobile tumors, without collaterally damaging
nearby critical structures. METHODS: The approach uses the concept that the
integral of balanced forces over the moving surfaces is directly proportional to
the lung volume changes. The respiratory motions, representing the lung volume
variations, were measured with the dynamic volume under the moving surfaces of
the thorax and abdomen. Sequential surface images on several patients and
volunteers were acquired for the feasibility study. Respiratory motions were
repeatedly measured on volunteers undertaking a quiet (normal) or a forced (deep)
breath. The dynamic volume under the moving surfaces were robustly fitted with a
linear trend and a trigonometric wave function that was compared with the fitted
curves for target moving trajectories derived from forty 4D-CBCT scans. RESULTS:
A large chest wall superior-outward movement was the unique characteristic of a
forced breath that had doubled the volume variations and elongated the
respiration period from quiet breath of ~4 seconds to >6 seconds. Under a quiet
breath, target motion trajectories could be easily described by single sine
functions that were consistent with dynamic surface volume modeling except for
having different motion amplitudes. The accuracy in synchronization of the real
time surface motion with respiration motion was within the measurement
uncertainty of ~2 mm. CONCLUSIONS: The analytical results with a hypothetical
single sine platform allow us to accurately predict internal target motion with
use of real-time video images. Synchronization of dynamic volume with respiratory
motion appears applicable for association of 4D medical imaging with 4D
videoimaging.
PMID- 28517401
TI - SU-D-211-05: A Systematic Analysis of Penumbra Characteristics in Conformai Arc
Delivery for SBRT and Its Utilization for Negative Margin Technique (NMT), a
Novel Planning Strategy for Improving Dose Conformation.
AB - PURPOSE: To systematically analyze penumbra characteristics in co-planar arc
beams and demonstrate how optimal aperture margin (OAM) can be systematically
estimated. METHODS: Full arc-beam delivery was simulated with a Pinnacle RTP for
a total of 32 cases. Considered factors were energy (6X, 6F, 10X, and 10F, where
'F' indicates flattening-filter-free), field-size (2*2, 4*4, 6*6, and 8*8), and
two materials (50*50*50 cm*cm*cm water and 50*50*50 cmxcmxcm water with a 20 cm
diameter sphere of 0.25 g/cc lung density at the center). The highest-dose
gradient (HDG) and its range in both radial-dose-distribution (RDD) and
longitudinal-dose-distribution (LDD) were evaluated. For OAM estimation, start
with simulated dose distributions in interest. Measure coverage size (CS) at the
chosen PIL in the RDD. The difference between the target size (TS) and the CS is
the margin needed. In radial-direction, choose a PIL where the CS is larger than
the TS [resulting in 'negative margin (NM)'] to enhance conformation
capability.Next, measure the CS at the chosen PIL in the LDD. Longitudinally,
positive margin is expected in general. This process was applied to 6X and 10F
cases in lung to illustrate its applicability. RESULTS: Overall, larger HDG was
observed in 6 MV (than 10 MV), smaller fields, LDD (than RDD), and in water (than
lung). 6F showed slightly larger HDG than 6X while 10X did than 10F. Dose fall
off started significantly farther from the CAX in RDD than LDD, supporting the NM
concept. With the systematic margin estimation applied, expected PILs matched
closely with isodose points having tight target coverage, indicating the
applicability of the method. CONCLUSIONS: Among tested, the 6F beam provides the
most optimal dose distribution for dose conformation. The range of optimal PIL
decreases as field-size increases. It has been demonstrated optimal AMs can be
systematically estimated as proposed in this study.
PMID- 28517402
TI - SU-D-217A-02: Effects of Enegy-Window Width and Spectral Effective Energy on
Estimation of Gamma Camera Deadtime Using the Decay Method.
AB - PURPOSE: Assessment of count-rate performance (CRP) is part of routine quality
assurance (QA) for gamma cameras. Manufacturers often specify deadtime (t) based
on the NEMA decay method (NEMA 1-2007). The spectral conditions prescribed by
NEMA are often difficult to duplicate during routine clinical QA testing and the
appropriate energy window is poorly defined. The objective of this investigation
is to evaluate the effects of energy-window selection and spectral conditions on
estimates of t using the NEMA decay method. METHODS: CRP was evaluated
intrinsically over a period of 48 hours with Tc-99m for two Siemens Symbia gamma
camera detectors using the NEMA decay method. CRP measurement was repeated with
varying amounts of scattering material (0-8 cm of acrylic) placed between the
source and detectors to transform the incident spectrum. CRP measurements were
also repeated using different photopeak-window widths (2-75%) as well as an open
energy-window. The CRP data were fit to the paralyzable detector model via non
linear least-squares minimization to estimate t. RESULTS: Estimates of t
increased linearly with decreasing spectral effective energy. The effective
energy was varied from 142-to-99 keV, which consequently altered the estimates of
t by ~0.095MUs or 21% (p<0.01). Additionally, estimates of t increased as a power
law when the fraction of measured counts in the photopeak window decreased
relative to open-window (total) counts. The ratio photopeak-window counts to open
window counts were varied from 1-to-0.12 which consequently altered the
estimates of t by ~8MUs or 180%. The estimated change in t between 15% and 20%
photopeak window is -0.13MUs or 12.5%. Repeat measurements demonstrated that
estimates of t using the decay method are precise to <2%. CONCLUSIONS: Deadtime
(t) determined using the decay method varied significantly with the spectral
effective energy and photopeak-window width. Careful attention to measurement
conditions are imperative when measuring t using the decay method for comparison
against manufacturer's specifications or trending as part of routine QA program.
PMID- 28517403
TI - SU-D-217A-05: Auto-Registration of Cardiac PET/CT Images with a 3D Weighted
Gradient Correlation Algorithm.
AB - PURPOSE: To design a novel 3D automatic registration algorithm for cardiac PET/CT
registration using gradient information and to evaluate the performance of the
algorithm with clinical PET/CT datasets. METHODS: The 512*512*47 CT images are at
first resized to 128*128*47 to match the matrix size of PET. In order to maximize
the gradient information at boundaries in CT, a conventional fuzzy c-means
clustering algorithm (number of cluster = 7) is implemented to suppress signals
from tissues that do not contribute much useful information for the registration
purpose (fat, lung, and bones). The 3D Image gradient map, consisting of all
three orthogonal components, is derived from the PET images and the post-
clustering CT images. The mis-registration is modeled as 3D rigid body
translation in this study, though it can be extended to include rotations as
well. The details of the gradient-based objective function are described in the
support document. Optimal registration is determined by searching for the maximum
of the objective function over a range of potential translation positions (e.g.
8.2*8.2*2.8cm). This process is repeated at a higher matrix size (512*512*47) to
refine the result of registration. RESULTS: We applied this auto registration
technique on 55 patient data sets of cardiac PET/CT images. The CT images were
average-CT images, and the PET images were without attenuation correction. 54 out
of the 55 cases produced satisfactory registration. CONCLUSIONS: The proposed
weighted gradient correlation algorithm is a viable solution for auto
registration of cardiac PET/CT images. More work is needed to further improve the
robustness of thealgorithm.
PMID- 28517404
TI - SU-E-E-04: Building and Strengthening the First Master's Program in Medical
Physics in The Gulf Region.
AB - PURPOSE: The first medical physics Master's program in the Arabian Gulf region
was started in 2002 at King Fahd University of Petroleum & Minerals (KFUPM),
Dhahran, Saudi Arabia. METHODS: After consulting with national and international
representatives from the AAPM, IOMP, the University of Wisconsin-Madison and King
Faisal Specialist Hospital and Research Center (KFSHRC) we constructed a
versatile and rigorous curriculum. The program requires the completion of 7 core
courses, 7 required labs, a minimum of 3 elective courses, a research project, a
four-month clinical rotation and passing and a comprehensive examination. The
success of the program required very close collaboration with national hospitals
such as King Fahad Specialist Hospital in Dammam (KFSH-D), KFSHRC, and Riyadh
Military Hospital. We cemented the collaboration with a formal agreement between
KFUPM and KFSH-D, whereby the clinical medical physicists are actively involved
in teaching lectures and labs, evaluating students' performance and co
supervising their clinical rotation and research projects. In order to prepare
our graduates for their medical physics careers, we emphasize innovative learning
methods such as students centered learning, execution of course projects,
experiential learning and acquiring research skills and tools such as Monte Carlo
simulations. RESULTS: Our graduates have succeeded in securing clinical positions
in some of the best hospitals in the region and achieved high employer
satisfaction. Some students have gone to pursue their PhD's in North America and
Europe. Many of our students succeeded in publishing their projects in
international journals and international conferences. One of our students was
instrumental in obtaining a US patent (US Patent # 785298) for an innovative x
ray tube design. CONCLUSIONS: We have achieved national recognition through the
excellence of our graduates. In order to maintain high education quality
standards and achieve international recognition, we are presently working to
acquire IAEA approval and CAMPEP accreditation.
PMID- 28517405
TI - SU-D-213CD-05: Identifying Prostate Brachytherapy Seeds at MRI: A Study in
Phantom.
AB - PURPOSE: Conventionally, post-implant CT scans are used for identification of
prostate brachytherapy implant seed locations. The dosimetric quality of the seed
implant in our institution is evaluated based on CT/MRI fusion and contouring of
prostate and rectal wall on MRI. Post-implant evaluation of prostate
brachytherapy using MRI alone is generally not feasible due to the uncertainty
associated with seed localization despite its excellent anatomical delineation.
The fusion of CT and MRI has some variability and may be time consuming. The goal
of our current work was to use SWI phase images for identification of prostate
brachytherapy seeds. Using MRI alone to identify seeds will eliminate the need
for CT scan of the patient post-implant and eliminate the variability of the
CT/MRI fusion. METHODS: A prostate gel phantom containing five inactive brachy
seeds (Advantage I-125TM, Biocompatibles, Oxford, CT) each has longitudinal cross
section area of 3.6 mm2. It was assessed using CT, and MRI. Imaging was done
using a GE Signa 3T HD MRI system (GE Heathcare, Millwaukee, WI). Imaging
parameters for SWI were: 512*384 (zero filled to 512*512), FOV=10 cm, ASSET
factor=2, TE/TR=20/42 ms, FA=15 degrees , RBW= 80 Hz/pixel, spatial
resolution=0.3 * 0.3 * 2.0 mm. RESULTS: Brachytherapy seed, as confirmed on CT
images, were easily identified in the phantoms on the filtered SWI phase images.
The mean area for the 5 seeds, as measured on CT and SWI filtered phase images,
was 3.5+/-0.5 mm2 and 3.8+/-0.6 mm2 , respectively. There appeared to be linear
relationship in seed area as determined by SWI filtered phase compared to CT
(R2=0.8). CONCLUSIONS: With the improved resolution, SNR and proper filtering on
high field MRI systems, SWI phase images can be used to identify prostate
brachytherapy seeds on conventional MRI without using CT.
PMID- 28517406
TI - SU-D-213AB-01: Dosimetry Improvement and Needle Number Reduction in Prostate
Brachytherapy Using Electromagnetically Guided Needle Placement.
AB - PURPOSE: To investigate dosimetry improvement in prostate brachytherapy by
conforming needles to urethral and prostate shape using an electromagnetic
tracking device. METHODS: We have reported a needle tracking system using an
electromagnetic sensor embedded inside the tip of the needle to improve needle
reconstruction accuracy and efficiency in conventional prostate HDR
brachytherapy. Utilizing the same system, we propose to guide needle insertion
following pre-optimized tracks based onthe target shape. In this study, we
investigate possible dosimetry improvement and needle number reduction by
comparing plans using the conventional implant method and the proposed method.
Twelve prostate brachytherapy patients were selected and studied retrospectively.
New virtual plans were created using the proposed method and conforming needle
tracks to the urethral and prostate shapes. Same optimization constraints were
applied to both the conventional and the new plans. DVH parameters and total
needles used have been analyzed to quantify dosimetry improvement and potential
toxicity sparing due to reduction in implant needles. RESULTS: Prostate volumes
are 41.16+/-13.27 cc. Number of needles used for the conventional plan is 16.6+/
1.2, vs. 13 for all the new plans. The prostate volume receiving 100% (V100),
125% (V125), and 150% (V150) of the prescription dose in conventional plans vs.
those in the new plans are 99.48%+/-0.21% vs. 99.53%+/-0.20%, 53.90%+/-5.61% vs.
50.30%+/-5.23%, and 25.37%+/-4.91% vs. 20.96%+/-3.41%, respectively. The
corresponding urethra V100 and V110 are 90.96%+/-3.10% vs. 85.78%+/-7.76% and
2.06%+/-1.23 vs. 0.46%+/-0.28%. CONCLUSIONS: The needle numbers and the urethral
V110 in the new plans are significantly lower than those in conventional
plans(p<0.001 and p=0.004, respectively), with no significant changes in doses
tothe prostate. Conformai needle implant following pre-optimized tracks with
electromagnetic guidance may significantly reduce acute and late toxicities in
prostate brachytherapy by reducing the number of needles and theurethral doses.
PMID- 28517407
TI - SU-D-218-03: Resonant Frequency of Rotating Anode X-Ray Tubes.
AB - PURPOSE: To evaluate a new rotating anode X-ray tube from the resonant frequency
point of view for stable and safe operation, and to validate a finite element
model for insight into X-ray tube rotor dynamics and vibration. METHODS: The 3
dimensional FEM model of the X-ray tube motor has been developed using ANSYS and
COMSOL. The resultant resonant frequency from the FEM simulation is substantiated
by experiments. During deceleration of the X-ray tube, an accelerometer and a
corresponding amplifier send the time domain vibration response to a spectrum
analyzer which generates the power spectrum. In the frequency domain analysis, a
peak signifies large vibrations at that frequency. To corroborate the FEM model,
the resonant frequency of the motor assembly without the anode attached was also
measured. Lastly, a rough estimate of the resonant frequency can also be observed
in angular speed curves which are obtained utilizing a quadrature position
sensor. RESULTS: The first mode resonance is expected at 20.3 Hz from the FEM
simulation. This result matches closely with the peak at 22.2 Hz in the power
spectrum and the location of the abrupt decreasing acceleration (slope) in the
speed curve at 22 Hz. Without the anode, the FEM simulation result of 35.1 Hz is
equal to the first peak at 35.1 Hz, and the angular acceleration is suddenly
reduced at 34.4 Hz. CONCLUSIONS: For image-guided interventional procedures using
a hybrid system, the X-ray tube should create flux at various times requiring
repeatedacceleration and deceleration of the motor. Hence it is ideal that the
resonant frequency is higher than operational speed, although alternatively the
motor could accelerate through the resonant frequency quickly. Design
improvements to modify the location of resonance of our motor assemblyare
underway using the verified FEM model. NIH R01 EB007626, Richard M. Lucas
Foundation.
PMID- 28517408
TI - SU-D-BRCD-06: Measurement of Elekta Electron Energy Spectra Using a Small
Magnetic Spectrometer.
AB - PURPOSE: To demonstrate how a small magnetic spectrometer can measure the energy
spectra of seven electron beams on an Elekta Infinity tuned to match beams on a
previously commissioned machine. METHODS: Energyspectra were determined from
measurements of intensity profiles on 6"-long computed radiographic (CR) strips
after deflecting a narrow incident beam using a small (28 lbs.), permanent
magnetic spectrometer. CR plateexposures (<1cGy) required special beam reduction
techniques and bremsstrahlung shielding. Curves of CR intensity (corrected for
non- linearity and background) versus position were transformed into energy
spectra using the transformation from position (x) on the CR plate to energy (E)
based on the Lorentz force law. The effective magnetic field and its effective
edge, parameters in the transformation, were obtained by fitting a plot of most
probable incident energy (determined from practical range) to the peak position.
RESULTS: The calibration curve (E vs. x) fit gave 0.423 Tesla for the effective
magnetic field. Most resulting energy spectra were characterized by a single,
asymmetric peak with peak position and FWHM increasing monotonically with beam
energy. Only the 9-MeV spectrum was atypical, possibly indicating suboptimal beam
tuning. These results compared well with energy spectra independently determined
by adjusting each spectrum until the EGSnrc Monte Carlo calculated percent depth
dose curve agreed well with the corresponding measured curve. CONCLUSIONS:
Results indicate that this spectrometer and methodology could be useful for
measuring energy spectra of clinical electron beams at isocenter. Future work
will (1) remove the small effect of the detector response function (due to
pinhole size and incident angular spread) from the energy spectra, (2) extract
the energy spectra exiting the accelerator from current results, (3) use the
spectrometer to compare energy spectra of matched beams among our clinical sites,
and (4) modify the spectrometer to utilize radiochromic film.
PMID- 28517409
TI - SU-D-BRA-05: Prostatectomy Patient's Bladder and Rectum Inter-Fraction Organ
Motion and Deformation Can Be Described by a Gaussian Signed Distance Field.
AB - PURPOSE: The inter-fraction organ motion/deformation can be conveniently modeled
using Bayesian theory with Normal-gamma conjugate prior if signed distance from
any fixed point in space to surface of the organ of interest obeys normal
distribution. In this study, we investigated whether the inter-fraction
motion/deformation of bladder and rectum observed from clinical prostatectomy
patients satisfy this normality condition. METHOD AND MATERIALS: 285 treatment
planning CT and daily CT-on-rails scans from 7 prostatectomy patients were used
in this study. Both bladder and rectum were contoured on all scans. Each
patient's daily CT-on-rails scans were registered to his treatment planning CT
and the bladder/rectum contours were mapped into treatment planning CT space for
analysis. A cubic box with orientations along treatment planning CT image axes is
defined to contain all bladders/rectums with 2cm margin. For each voxel inside
this box (size: 2mm*2mm*1.5mm), its distance to the bladder/rectum surfaces was
measured. Sign is added to the distance to indicate whether a point is inside or
outside of an organ of interest. Now the inter-fraction motion/deformation of
bladder/rectum can be characterized by the distance variation from the voxels to
the bladder/rectum surface. Jarque-Bera normality statistical test was employed
to examine whether the signed distances obey normal distribution. RESULTS: For
each patient, the signed distance to bladder or rectum from at least 99.99% of
the voxels passed the Jarque-Bera test with p-value 0.05. CONCLUSIONS: For
prostatectomy patients, their bladder or rectum inter-fraction organ
motion/deformation can be statistically described by a Gaussian signed distance
field. This makes it possible to use Bayesian statistics model with Normal-gamma
conjugate prior to predict bladder or rectum daily location and shape during a
prostatectomy patient fractionated radiotherapy.
PMID- 28517410
TI - SU-C-218-06: Evaluation of a CT-Based, Semi-Automated Lung Mass Estimation Method
Under Varying Acquisition Conditions.
AB - PURPOSE: To evaluate a simple, semi-automated lung mass estimation method on CT
scans from a variety of acquisition techniques for mass correction of MIRD dose
estimates. METHODS: CT scans from ten patients undergoing stereotactic body
radiation therapy treatment planning on a GE DST PET/CT scanner were analyzed
retrospectively. For each patient, free- breathing (FB) and respiratory gated 4D
CT scans were acquired. 4D-CT scans were reconstructed and sorted into ten phases
representing one complete respiratory cycle. An average CT (ACT) was derived from
the ten phase reconstructions. Half the patients also had breath-hold (BH) scans.
Scans were analyzed using Osirix MD's V 1.3 (Pixmeo, Geneva Switzerland) Grow
Region segmentation tool. Lung volume; average lung, tissue (~lcm ROI in the
descending aorta), and air (~1 cm ROI in the trachea) HU's were recorded for each
acquisition type. Lung mass was calculated by assuming each voxel is a linear
combination of only air and tissue. The fraction of total lung volume consisting
of lung tissue is assumed to be (lung HU - air HU) / (tissue HU - air HU), and
mass = total volume X fraction X 1 g/cm3 . RESULTS: 4D-CT mass estimates showed
variability, with a minimum at end-expiration and a maximum just after end
inspiration. ACT generally produced the highest estimate. FB and BH estimates
were near the median. CONCLUSIONS: Although calculated mass increased with
increasing total lung volume, the difference between minimum and maximum
population means in the 4D-CT data was 5.5%. FB and BH estimates fell within that
5.5%, while the ACT mean was 9.8% above the global mean. The range of estimated
masses (524 g to 977 g) suggests the value of lung mass estimates for more
patient-specific MIRD dose assessment. Excluding ACT, the results indicate that
any of the acquisition techniques can provide a reasonable lung mass estimate.
This work was supported in part by a residency grant from the AAPM.
PMID- 28517411
TI - SU-D-217BCD-03: Impact of Jaw Width on the Megavoltage Computed Tomography Image
Quality and Imaging Dose with Helical Tomotherapy.
AB - PURPOSE: On-treatment megavoltage computed tomography on Helical Tomotherapy
(Accuray Inc., Sunnyvale, CA) is critical for image guided radiotherapy. A
strategy was developed to assess the impact of various jaw widths on image
quality and imaging dose with Tomotherapy. METHODS: A cheese phantom (Gammex RMI,
Middleton, WI) made of water equivalent materials was employed in this study.
Three sets of measurements were independently carried out. Firstly, in the
imaging dose measurement, the phantom was placed on the couch and aligned with a
stationary green laser and beam isocenter. The measurement point was 10 mm up
from the cente of the phantom. Three slices on either side of the middle slice
were selected. Secondly, two inserts with different rows of holes of various
sizes were placed inside the phantom for image contrast and resolution
investigation. Lastly, twelve density inserts were placed into the outer holes in
the phantom for measurement of the image value to density table (IVDT). A
comparison of imaging dose, image resolution and contrast, IVDT table between
different jaw configurations was performed to evaluate the imaging system.
RESULTS: Imaging dose was 2.93 cGy with a jaw size of one mm as opposed to 1.62
cGy with a four mm jaw, both of which are below the vendor's requirement: 3 cGy.
However, image quality is improved significantly with the smaller jaw. Four lines
of holes can be readily identified on images using smaller jaw while only three
lines visible with the larger jaw. Image contrast is similarly enhanced when
reducing the jaw size. On average CT numbers are 6% higher with the smaller jaw
than those obtained with the larger one. CONCLUSIONS: Significant improvement in
image quality is achieved with the smaller jaw field in Tomotherapy while the
imaging dose is kept at a clinically acceptable level.
PMID- 28517412
TI - SU-D-213AB-05: Commissioning a CT Compatible LDR T&O Applicator Using Analytical
Calculation with ID and 3D Dosimetry.
AB - PURPOSE: To determine the characteristics of a new commercially available CT
compatible LDR Tandem and Ovoid (T&O) applicator using 3D dosimetry. METHODS: We
characterized source attenuation through the asymmetric gold shielding in the
buckets by measuring dose with diode and 3D dosimetry and compared to an
analytical line integral calculation. For 3D dosimetry, a cylindrical PRESAGE
dosimeter (9.5cm diameter, 9.2cm height) with a central 6mm channel bored for
source placement was scanned with the Duke Large field of view Optical CT-Scanner
(DLOS) before and after delivering a nominal 7.7Gy at a distance of 1 cm using a
Cs-137 source loaded in the bucket. The optical CT scan time lasted approximately
15 minutes during which 720 projections were acquired at 0.5 degrees increments,
anda 3D dose distribution was reconstructed with a 0.5mm3 isotropic voxel size.
The 3D dose distribution was applied to a CT-based T&O implant to determine
effect of ovoid shielding on the dose delivered to ICRU 38 Point A as well as
D2cc of the bladder, rectum, bowel, and sigmoid. RESULTS: Dose transmission
through the gold shielding at a radial distance of 1-3cm from midplane of the
source was 86.6%, 86.1, and 87.0% for analytical calculation, diode, and 3D
dosimetry, respectively. For the gold shielding of the bucket, dose transmission
calculated using the 3D dosimetrymeasurement was found to be lowest at oblique
angles from the bucket witha minimum of ~51%. For the patient case, attenuation
from the buckets leadto a decrease in average Point A dose of ~4% and decrease in
D2cc to bladder, rectum, sigmoid, and bowel of 2%, 15%, 2%, and 7%, respectively.
CONCLUSIONS: The measured 3D dose distribution provided unique insight to the
dosimetry and shielding characteristics of the investigated applicator, the
technique for which can be applied to commissioning of other brachytherapy
applicators. John Adamovics is the owner of Heuris Pharma LLC. Partially
supported by NIH Grant R01 CA100835-01.
PMID- 28517413
TI - SU-D-BRB-04: FDG-PET Histogram Distances: Novel Predictors of Tumor Response to
Chemoradiotherapy.
AB - PURPOSE: To examine the accuracy of FGD-PET histogram distances as predictors of
pathologic tumor response to chemo-radiotherapy (CRT) in esophageal cancer.
METHODS: Twenty patients were included. A rigid registration was used to align
the post-CRT PET/CT with the pre-CRT PET/CT images. The primary tumor was
delineated using a region-growing algorithm with a threshold of SUV = 2.5 on the
pre-CRT PET. Two histograms of SUVs within the tumor were constructed on the pre
CRT PET and registered post-CRT PET, respectively. The differences between the
two histograms reflected changes in the SUV distribution and were therefore
potential predictors of tumor response. The differences were quantitatively
measured by histogram distances using 12 bin-to-bin and 8 cross-bin algorithms.
The accuracy of histogram distances in predicting pathologic tumor response to
CRT was measured using the area under ROC curve (AUC), prediction accuracy, and
the Mann-Whitney tests, in comparison with traditional PET response measures and
texture features. RESULTS: Cross-bin histogram distances were shown to be
significant (p<0.05) predictors of pathologic tumor response. They were more
accurate than bin- to-bin histogram distances (not significant). The most
accurate cross-bin histogram distances were: Quadratic-Chi distance (AUC=0.89,
accuracy=80%, p=0.003), Earth Mover distance (AUC=0.83,accuracy=80%, p=0.014),
diffusion distance (AUC = 0.82, accuracy=85%, p=0.02) and Match distance (AUC =
0.79, accuracy=80%, p=0.03). This family of novel predictors were more accurate
than traditional PET response measures using SUVmax (AUC=0.76, accuracy=75%,
p=0.05), SUVpeak (AUC=0.74, accuracy=70%, p=0.08), Total Glycolytic Volume
(AUC=0.76, accuracy=70%, p=0.05), as well as texture features based on the
cooccurrence matrix (Inertia: AUC=0.85, accuracy=80%, p=0.01). CONCLUSIONS: The
cross-bin histogram distances characterized changes in the SUV distribution
within a tumor and showed high accuracy for the prediction of pathologic response
to CRT in esophageal cancer. This workwas supported in part by the National
Cancer Institute Grant R21 CA131979.
PMID- 28517414
TI - SU-D-213CD-02: The Accuracy of AlignRT Guided Set-Up for Whole Breast and
Chestwall Irradiation.
AB - PURPOSE: To evaluate the ability of AlignRT (VisionRT Ltd., London, UK) to
accurately position patients receiving whole breast or chestwall irradiation and
the impact of AlignRT on portal image dose. METHODS AND MATERIALS: Twenty whole
breast or chestwall cases set-up using AlignRT at our site were compared to a
series of 20 similar patients set-up without the use of AlignRT over the same
time span. All patients were set-up head first supine, on a Quest Breastboard
(Qfix, Avondale,PA). The AlignRT patients were positioned with an AlignRT region
of interest that encompassed the ipsa-lateral chest minus the breast tissue drawn
on a surface created from the patient contour generated in treatment planning.
Non-AlignRT patients were positioned using skin marks added in simulation.
Positional accuracy was verified by qualitative evaluation of portal imaging on
the first treatment day, then once weekly. RESULTS: The percentage of port images
that were deemed unacceptable by therapists or radiation oncologists (> 3 mm
deviation from simulation position) was 7.5 +/- 8.1% for the AlignRT group (with
a range of 0 - 15%). In 14 of the 20 cases, one or fewer port images were
unacceptable over the entire treatment. For the non-AlignRT group 20 +/- 14% (0
45%) of the images were unacceptable. In only 6 of the 20 cases one or fewer port
images were found to be unacceptable over the course of treatment. CONCLUSION: As
judged by port images, AlignRT is able to provide a more accurate positioning of
whole breast and chestwall patients, with a reduction in port dose and in set-up
time, compared to the use of lasers and skin marks. The reduced number of
rejected port images strongly suggests that AlignRT gives a more consistent,
reproducible set-up on non- port days than skin marks alone.
PMID- 28517415
TI - SU-D-211-04: Sector Intensity Modulated (SIM) Gamma Knife Stereotactic
Radiosurgery.
AB - PURPOSE: The latest Gamma Knife (GK) system, Perfexion, consists of 192 Co-60
sources divided into eight sectors. Treatment delivery includes multiple shots
placed at different positions. For every shot, each sector can be either blocked
or open with four different aperture sizes. However, the beam-on time is designed
to be fixed. We proposed an innovative concept, Sector Intensity Modulated (SIM)
Gamma Knife by dynamically varying the beam-on time for each individual sector to
improve stereotactic radiosurgery planning quality. METHODS: The anatomic
structures and dose matrices from each sector for every shot were obtained from
the GK workstation. The beam-on time for each sector was decomposed with various
discrete levels and brute-force algorithm was used to get the optimal solution.
The resulting SIM plan was then re-entered into the GK workstation. Six indices
were used to benchmark the plan quality: Coverage, Conformality, Gradient,
Maximum Dose(s) to critical structure(s), Volume receiving over 8 and 12 Gy. All
the SIM plans in comparison with the original plans were further reviewed by an
experienced oncologist. RESULTS: The simulations were tested on various pituitary
adenoma cases. Results consistently showed that SIM yielded better plans with all
quantitative indices improved compared to original plan. It provides better
conformality, quicker drop off of the isodose line outside the tumor, lower doses
to the critical structures as optical- nerve/chiasm while maintaining at least
99% coverage of the tumor. Results were more favorable according to oncologist's
view. In particular, up to 20% or 0.6 cc volume decrease in healthy tissue
receiving 8 Gy was observed. This may translate into clinically observable
reduction in acute/late toxicities. CONCLUSIONS: Our preliminary results show
that Sector Intensity Modulated Gamma Knife offers superior treatment plans
compared to the originally delivered plans. Further works as adding dynamic shot
location and dynamic shot shaping will be discussed.
PMID- 28517416
TI - SU-D-217A-01: A High-Resolution in Vivo Molecular Imaging Technique Based on X-
Ray Fluorescence.
AB - PURPOSE: Traditional molecular imaging techniques such as PET/SPECT have many
limitations, including relatively low spatial resolution, short lifetime of
radioisotope probes, limited availability due to reliance on cyclotron,
relatively high dose, and lack of effective molecular probes for certain tumor
cells. In this work we demonstrate the feasibility of a novel x- ray fluorescence
molecular imaging (XFMI) technique using high-power carbon nanotube (CNT) x-ray
array technology. The XFMI overcomes some limitations and will be a significant
advance in molecular imaging technology for cancer drug development and cancer
biology research. METHODS: A testing chamber was constructed containing two
Amptek energy-resolving detectors analyzing a copper collimated fluorescence beam
placed opposite each other symmetric about the sample and perpendicular to the
primary incoming x-ray beam, also using the copper collimator. Different
concentrations of indium trichloride and iodine were tested to determine the
minimum detectable concentration (MDC) for each. RESULTS: The MDC for indium was
found to be 80 ug/mL and 100 ug/mL for iodine at 50 kVp, 30mAs (5 minutes imaging
time). This is on the order of magnitude of the MDCs determined at large
synchrotron facilities using XFI. Higher concentrations above 1mg/mL of both
elements were detectable at 1.5 mAs (15 seconds). CONCLUSIONS: These results show
that it is possible to not only measure low concentrations of the above elements,
but also distinguish between similar L-alpha peaks. This allows for future work
of obtaining 2D and 3D imaging to determine element types and concentrations
diffused in different parts of the body. Carolina Center of Cancer
Nanotechnology, University Cancer Research Fund.
PMID- 28517417
TI - SU-D-BRCD-03: Spectroscopic Characterization of a 6 MV Linear Accelerator Field
Using Compton Spectrometry Measurements and Monte Carlo Techniques.
AB - PURPOSE: Effective treatment planning for radiotherapy is dependent on accurate
spectra determination; however, direct measurements of spectra arecomplicated by
fluence rates that exceed detection system limitations. This work demonstrates
the potential to use a Compton scattering technique to measure the spectrum of a
6MV linac. These spectra are further characterized using Monte Carlo (MC)
simulations. METHODS: A high-purity germanium detector was used to measure the
photon spectrum scattered at35 degrees from the central axis of 3cmx3cm and
lOcmxlOcm 6MV fields from a Varian linac. Photons were scattered using aluminum
rods positioned at isocenter, and were admitted to the detector through a 30cm
long collimating aperture. The measured Compton-scattered spectra were corrected
for background. An MC model of the linac was developed in MCNP5 to calculate
central- and off-axis spectra. The model geometry was verified by comparisons
with percentage depth-dose and profilemeasurements. The spectroscopic effect of
the mean energy, radius, and divergence of the electron beam incident on the
target was tested for twofield sizes. RESULTS: The count rate of the scattered
beam increased with field size and scattering rod diameter. Preliminary
measurements indicate that the spectrum was shifted to lower energies using this
technique; however, the signal-to-noise ratio was poor due to leakage and room
scatter. MC simulations demonstrate that the central- and off-axis spectra were
sensitive to changes in mean electron energy; however, changes in beam diameter
and angular divergence did not substantially affect either the central- or off
axis spectra. CONCLUSIONS: This work demonstrates that the spectrum from a 6MV
linac can be measured using Compton spectrometry. Further work is required to
increase the signal-to-noise ratio and correct fordetector response. MC
simulations indicate that the spectra were sensitive to variations in the
parameters used to define the primary electron beam incident on the target.
PMID- 28517418
TI - SU-D-217A-04: Evaluation of the Spatial Concordance Between the Intratumoral
Patterns of 18F-FLT and 18F-FDG Uptake in a Small Animal Tumor Model.
AB - PURPOSE: PET imaging allows for the visualization of tumor microenvironment and
identification of aggressive or radioresistant tumor subvolumes that can be
targeted with an escalated radiation dose. Multiple PET tracers have been
developed for visualization of different aspects of tumor microenvironment;
however, the spatial distribution of tracers in tumors is equally affected by
tumor tissue viability and tracer delivery limitations. Given these issues and
the low resolution associated with PET imaging, two different PET tracers can
produce very similar images. Therefore, it is important to demonstrate that a
novel PET tracer does provide additional useful information to that obtained with
other tracers. This study investigates the added value of performing 18F-FLT PET
imaging as well as 18F-FDG imaging. METHODS: Head and neck tumor xenografts grown
in nude mice were used to study intratumoral tracerdistributions. 18F-FDG and 18F
FLT PET images were obtained on subsequent days using a small animal PET/CT.
Pinnacle 9 was used to deformably register the CT image from the FLT PET/CT to
the FDG PET/CT image set. The generated deformation was applied to the FLT PET
image to achieve an unbiased FLT to FDG PET image registration. The Pearson
correlation coefficient between FDG and FLT was calculated voxel- by-voxel within
a tumor contour. Overlap analysis of thresholded tracer distributions was carried
out by comparing Dice similarity coefficients. RESULTS: Both SQ20B and FaDu
tumors showed a moderate voxel-by-voxel correlation between FDG and FLT
intratumoral patterns of uptake with an average rho value of .56 and .63
respectively (range .37-.76) despite significant differences in tumor morphology.
The average volumes under thedice coefficient surface for SQ20B and FaDu tumors
were not significantly different. CONCLUSIONS: Despite being equally affected by
the issues of tracer delivery, necrosis and PET resolution, FDG and FLT PET
images displayed an observable difference at clinically relevant thresholds.
PMID- 28517419
TI - SU-E-E-03: Ethics and Professionalism Education in Medical Physics: A Needs
Assessment Study.
AB - PURPOSE: To perform a needs assessment survey of ethics/professionalism education
in medical physics and ethical/professional challenges in clinical,research and
educational settings with the intent of supplementing and customizing TG159
recommended ethics curriculum for medical physics trainees. METHODS: A web-based
survey was conducted among AAPM members to assess current practices, attitudes
and perceptions pertaining to ethics/professionalism education and
ethical/professional misconduct or questionable behavior and practices in the
field. RESULTS: The survey was distributed by AAPM to 7708 members via email;
1362 (17.7%) responded. Seventy-five percent of the respondents were male. Sixty
percent (805/1345) stated they received no education in ethics/professionalism.
Eighty-one percent (126/155) of current trainees received instruction in
ethics/professionalism, as opposed to 35% (392/1130) of those who are post
training. There was strong support (>90%) for continuing education in
ethics/professionalism; seventy-five percent (1019/1354) supported sessions on
ethics and professionalism at national meetings. Most preferred method of ethics
instruction was periodic discussion sessions involving faculty and trainees, with
the least interest expressed for a separate course. Many reported direct personal
knowledge of one or more instances of a variety of professional/ethical
misconduct or questionable behavior. Thirty eight percent (458/1192) reported
poor mentorship, with women reporting this concern more often than men
(129/281,46% versus 316/877, 36%, p<.05). Over one-fourth of respondents reported
being asked to perform low educational value tasks and expressed concerns about
fairness. A significant minority also reported questionable behavior with respect
to authorship assignment (346/920, 38%), data fabrication (107/924, 12%), data
falsification (94/919, 10%); concerns about research subject privacy and
confidentiality were lower (64/887, 7%). CONCLUSIONS: Data gathered through the
survey is guiding our efforts to develop a case-based ethics curriculum and
instructional materials for medical physics trainees at our institution. This
effort may be useful to other medical physics programs which offer ethics
training/education. This work has been funded in part by a grant from the
National Institutes of Health, T32 EB002103-22S1.
PMID- 28517420
TI - SU-D-211-06: The Effect of Motion in RapidArc Lung SBRT Delivery.
AB - PURPOSE: RapidArc is routinely used for stereotactic radiotherapy for lung
cancer. While treatment dose is optimized and calculated on a static CT image,
the motion of the target in conjunction with the motion of the MLC may Result in
a delivered dose deviating from the planed dose. In this study, we investigate
the dosimetric consequences of the inter-play effect by simulating dynamic dose
delivery on a dynamic CT dataset of real patients. METHODS: The target motion in
20 patients was analyzed and 5 patients with >10 mm motion were chosen for this
study. The RapidArc plan for eachpatient is optimized on a free-breathing CT
using 2 arcs. Inherent in each plan is data on the associated parameters such as
timestamp, MLC leave position, gantry angle and delivered beam MUs for each
control point. Simulated dynamic delivery is performed by associating these
parameters with each of the breathing phases of the 4D-CT. The starting breathing
phase is selected randomly for each of the two arcs. Dose from the derived
partial plans associated with each phase of the 4D-CT dose is recalculated in
Eclipse. Accumulation of dose is performed using deformable image registration
from each phase of the 4D-CT to the exhale phase of the 4D-CT. RESULTS: The
coverage of the GTV and PTV shows negligible variations from the interplay
effect. But the Homogeneity Index is affected by the motion. The prescription
isodose volume is smaller than what was from the treatment plan dose. There were
both intra- and inter-fraction effects seen inthe OARs dose in some patients.
CONCLUSIONS: We investigated the motioneffect in RapidArc Lung SBRT delivery in 5
patients. Negligible variations were shown for target coverage. However the
motion effects were observed in high dose distribution and volume. Some OARs dose
distributions were affected by the motion.
PMID- 28517421
TI - SU-D-218-02: 4D-MRI Based on Body Area (BA) Surrogate and Sagittal Image
Acquisition.
AB - PURPOSE: 4D-MRI based on body area (BA) surrogate using axial image acquisition
has been demonstrated. Since respiratory motion mostly occurs in the superior
inferior (SI) direction, it is expected that sagittal acquisition may provide
more robust and accurate breathing signal than axial acquisition. The aim of this
study was to investigate the feasibility of extracting breathing signals from
sagittal images using BA surrogate and its application in 4D-MRI. METHODS: 7
human subjects were imaged continuously in a single (n=5) or multiple (n=2)
sagittal planes using a steady-state precession sequence. Imaging parameters
were: TR/TE, 3.7ms/1.21ms; Matrix, 256*166; FOV, 350*300mm; flip angle, 52
degrees ; slice thickness, 5mm; frame rate: ~3 frames/s. Imaging time per slice
is 2 minutes for single slice acquisition and ~10 seconds for multi-slice
acquisition. Breathing signals were generated for all subjects by tracking the
change of BA. The multi-slice sagittal acquisition was performed on a MRI-
compatible motion phantom with a cylindrical gel target and was simulated on a 4D
digital human phantom. Breathing signals were extracted from the sagittal images
using the BA surrogate. Respiratory phases were calculated. 4D-MRI of both
phantoms were retrospectively reconstructed based on the respiratory phases.
RESULTS: Breathing signals extracted from both single slice and multi-slice
sagittal acquisitions showed stable and well- characterized patterns. 4D-MRI of
the physical phantom showed clear sinusoidal motion of the gel target in all
three planes with minimal artifacts. Simulated '4D-MRI' of the 4D digital phantom
matched well with original images: the mean absolute difference in motion
amplitude of the 'tumor' was 0.4+/-0.3mm. Small artifacts of discontinuity were
observed in the SI direction in certain phases. CONCLUSIONS: It is feasible to
extract breathing signals from sagittal images for 4D-MRI application. Further
investigation is needed to test whether sagittal acquisition is more robust and
accurate than axial acquisition for breathing signal extraction.
PMID- 28517422
TI - SU-D-BRCD-05: Evaluation of New Exit Detector Based Transit Dosimetry Software
for TomoTherapy Treatments.
AB - PURPOSE: The prospect of 3D transit dosimetry to verify treatment delivery is a
novel and emerging technology in TomoTherapy. Math Resolutions, LLC, has expanded
their Dosimetry Check (DC) quality control software to include transit dosimetry
calculations for TomoTherapy treatments. The data recorded by the MVCT detectors
during patient treatment is used in conjunction with the planning CT to calculate
the delivered dose to the patient from each fraction. This study presents a
summation of our experiences at the University of Virginia in collaboration with
Math Resolutions in verifying and implementing the transit-dose calculation
aspects of this new TomoTherapy specific product. METHODS: Low and high
modulation cheese phantom plans and clinical plans (prostate, GYN, pituitary, and
thoracic vertebra) were used to evaluate the DC transit dosimetry software. The
TomoTherapy planning CT, structure set, plan, and dose for each plan were
imported into the DC software. The fluence maps were reconstructed from the exit
detector data by correcting for patient attenuation and used to compute the
delivered dose. The resulting dose distribution is compared with the TPS planned
dose using isodose line comparison and gamma index. RESULTS: The percent
difference between the planned and DC calculated doses ranged between 0.63% for a
low modulation cheese phantom plan to 5.94% for a prostate plan. Using criteria
of 3%, 3mm, the gamma index passing rate for the tested plans ranged from 94.7%
to 99.1% <1 for the overall patient area and from 88% to 96.4% for the treatment
area receiving at least 80% of the prescribed dose. CONCLUSIONS: The results from
our evaluation of Math Resolutions' DC look promising and generally within an
acceptable range for portal dosimetry programs. Further investigations will
include developments to improve the DC algorithm and determine how it can best be
implemented in a typical TomoTherapy clinical workflow. Research Grant from Math
Resolutions LLC 01/12/2012-01/11/2013 Math ResolutionsTM Dosimetry Checksoftware
was given to UVa to assist with evaluating the precision of the product in
reconstructing dose from the TomoTherapy exit detector data.
PMID- 28517423
TI - SU-D-BRA-04: Improvement of Diaphragm Motion Reproducibility in MRI Using
Audiovisual Biofeedback for Lung Cancer Radiotherapy.
AB - PURPOSE: Previous studies have investigated the effect of AV biofeedback on the
external respiratory signal reproducibility. This is the first study
investigating the effect of AV biofeedback to improve the motion reproducibility
of the internal anatomy. The aim of the project is to test the hypothesis that AV
biofeedback improves the diaphragm motion reproducibility. METHODS: An AV
biofeedback system has been employed with MRI acquisitions. The AV biofeedback
system utilized (1) the external marker position on the abdomen using an RPM
system (Real-time Position Management, Varian) to audio-visually guide a human
subject for regular breathing and (2) a fast Gradient-Recalled-Echo (fGRE) MR
pulse sequence of 3 Tesla GE MRI (GE Healthcare) to monitor the diaphragm motion
(200ms). The improvement in the diaphragm motion reproducibility using the AV
biofeedback system combined with MRI has been assessed in 26 studies with 13
healthy human subjects. Each subject underwent two studies for assessment of the
diaphragm motion reproducibility both with AV biofeedback and without (free
breathing). The second study features a reversed order of breathing conditions.
The total MRI acquisitions across the 26 studies are 202 measurements including
sagittal and coronal planes. RESULTS: Average RMSE (root mean square error) of
diaphragm displacement obtained from MRI analysis has been reduced from 2.7mm of
free breathing to 1.6mm of AV biofeedback breathing (p-value < 0.05).
Additionally, the average RMSE of diaphragm motion period was reduced from 1.84s
with free breathing to 0.34s with AV biofeedback breathing (p- value < 0.05). 22%
of average displacement error was reduced using AV biofeedback in the first
study, and 47% reduction in the second study. CONCLUSIONS: The study demonstrated
the improvement in the diaphragm motion reproducibility using AV biofeedback.
This system can provide clinically applicable motion management of the internal
anatomy in MRI and for Image Guided Radiotherapy (IGRT).
PMID- 28517424
TI - SU-D-217BCD-02: Online Angular Tube Current Modulation in X-Ray Computed
Tomography: Can Tube Current Be Modulated Appropriately?
AB - PURPOSE: In X-ray computed tomography (CT), X-rays are significantly less
attenuated in the anteroposterior direction and more in the lateral direction.
Therefore, the tube current should be adjusted within one gantry rotation using
angular tube current modulation (TCM). The aim of this study was to evaluate
whether online angular TCM could reduce radiation dose appropriately. METHODS: A
128-detector dual-source CT (SOMATOM Definition Flash; Siemens Healthcare,
Erlangen, Germany) and an online TCM system (CARE Dose 4D; Siemens Healthcare)
were used. Dose profiles were acquired using the CT Dose Profiler (RTI
Electronics, Molndal, Sweden) and an elliptical cylindrical phantom (MHT; Kyoto
Kagaku, Kyoto, Japan) for helical CT scans with and without TCM. In addition,
absorbed dose distributions within a single section were acquired using an
anthropomorphic phantom (RANI 10; The Phantom Laboratory, Salem, NY) and
radiophotoluminescent glass dosimeters (RPLDs) (GD- 302M; Chiyoda Technol, Tokyo,
Japan) for helical CT scans with and without TCM after placing RPLDs within all
holes of one section and pasting them around the section. A graph of each
absorbed dose distribution was drawn using graphing software (ORIGIN 8.6;
OriginLab, Northampton, MA). RESULTS: The acquired dose profiles suggested that
online angular TCM could adjust the tube current in near-real time according to
the attenuation measured from the previous projection. The profiles gradually
stabilized because the tube current was adjusted properly. The absorbed doses
were low and the distributions were stable with TCM compared with those without
TCM. CONCLUSIONS: In X-ray CT, an online angular TCM can reduce radiation dose
effectively by adjusting tube current within one gantry rotation in near-real
time.
PMID- 28517425
TI - SU-D-213AB-04: Evaluation of the Dose Calculation in a Commercial Planning System
for a Breast Cancer Brachytherapy Technology Using Monte Carlo Simulation.
AB - PURPOSE: To evaluate the dose calculation in a commercial treatment planning
system (TPS) for a breast cancer brachytherapy technology using Monte Carlo
simulation for 21 patients. METHODS: Plans for 21 patients who received SAVI
treatments were modeled using data from the TPS including CT images, structures
and source information. The MC code PENELOPE was used, inputting images in voxel
format, where density and material (tissue, air, bone and Nitinol) for each voxel
were assigned based on its calibrated Hounsfield units and contoured structure
sets, respectively. For the source model only gamma-rays and fluorescence X-rays
of the NuDat database 192Ir spectrum were used, leaving out photons with emission
intensity less than 0.1% and X-rays with energies below 10 keV. Source positions
were entered into the plan and run individually. Dose was totaledby individually
weighting the dose for each source position using the original TPS plan dwell
times and then summing the weighted dose for all positions. RESULTS: Dose from
the Monte Carlo plan was compared with dose from the original plan using isodose
lines at 50, 100, 150 and 200% of the prescription dose of 34Gy. Dosimetric
coverage of the target was compared by evaluating the V100, V150 and V200 (volume
of the target covered by 100%, 150 and 200% of the dose respectively). The V200
and V150 had an average increase (and standard deviation) of 9.1% (3.2%) and 3.8%
(1.4%) respectively, while the average change in V100 was 1.2% (1.0%). Where
variance for the entire simulation was 0.9%. CONCLUSION: We have compared dose
distributions of a commercial TPS using Monte Carlo simulation for SAVI breast
cancer brachytherapy and found that a dose increase near the air-tissue
interface.
PMID- 28517426
TI - SU-D-218-06: Acceleration of Optical Photon Monte Carlo Simulations Using the
Macro Monte Carlo Method.
AB - PURPOSE: The purpose of this work is to demonstrate that optical photon Monte
Carlo simulations via a photon transport code called MCML can be accelerated
using macro Monte Carlo (MMC) techniques. METHODS: MCML was modified to
incorporate the macro Monte Carlo radiation transport method. The original MCML
uses scattering, absorption, reflection and refraction physics to transport
optical photons through multi-layered geometries. The code determines
transmission, reflection and absorption for the layered geometry specified by the
user. To make the code run faster, the MMC version of MCML uses large, multi
interaction steps in regions that are homogeneous. These large steps are pre
computed and stored in a database with many step sizes, materials and photon
energies. The MMC version of MCML determines whether large MMC steps or
traditional Monte Carlo should be used depending on the photon's current location
inthe geometry. RESULTS: The MMC version of MCML was tested against the original
MCML code for a number of simple test geometries. It was also tested in
anatomical geometries that are often uses in optical photon modeling. This
includes skin and skull geometries. In each case, the reflection and transmission
results from each code differed by less than 0.5%. The absorption data produced
by each code also differed by less than 0.5% in most cases, and never differed by
more than 2%. The MMC version of MCML runs between 1-3 times as many particles
per unit time comparedto MCML, depending on the geometry. CONCLUSIONS: Applying
Macro Monte Carlo methods to MCML produces a faster code without compromising
accuracy. The speed-gains are greatest in geometries thathave regions that are
large relative to the mean scattering length for photons in that region. This
work has the potential to accelerate light modeling for both photodynamic therapy
and near-infrared spectroscopic imaging.
PMID- 28517427
TI - SU-D-BRB-03: Prediction of Tumor Outcomes Through Wavelet Image Fusion and
Texture Analysis of PET/MR Imaging.
AB - PURPOSE: To investigate the combination of PET/MR image features for the early
prediction of tumor metastases to the lungs in soft-tissue sarcoma (STS) cancer.
METHODS: A dataset of 24 patients with histologically proven STS was used in this
study. All patients underwent pre-treatment FDG-PET and MR scans, which comprised
of T1 and T2-fat suppression weighted (T2FS) sequences. The patients had a median
follow-up period of 36 months (range: 6-69 months). Eight patients developed
metastases to the lungs.Tumors were contoured on the T2FS scans by an expert
physician. Fusion of the co-registered FDG-PET/MR scans was performed using a
wavelet transform technique. A SUV feature (SUVmax) from the FDG-PET scans and 6
texture features from the co-occurrence matrix of the fused scans were extracted
from the tumor region and correlation with the clinical endpoint of metastases to
the lungs was investigated. Statistical analysis was performed using Spearman's
rank correlation (rs) and multivariable logistic regression. RESULTS: The highest
univariate prediction was found on FDG-PET/T2FS fused scans analyzed using the
texture features "Sum-Mean" and "Variance". These two fused scan-texture feature
combinations reached rs = -0.6838 (p = 0.0003). In comparison, SUVmax reached rs
= -0.6257 (p = 0.0011). The highest multivariate prediction was found with the
following 3- parameter model: -3.15*SUVmax - 5.37*FDG-PET/T2FS-Sum-Mean +
0.57*FDG-PET/T1-Variance. This model reached rs = 0.7977 (p = 0.000005).
CONCLUSIONS: This work indicates the potential of PET/MR texture features of
tumors as complementary metrics to existing prognostic factors. Substantial
improvement in terms of prediction of metastases to the lungs in STS cancer was
found with the combination of texture features from fused FDG-PET/MR scans.
Potentially, this could improve patients' outcomes by allowing better adaptation
of treatments. Future work will involve evaluation of the robustness of the
proposed method and validation on a larger set of patients.
PMID- 28517428
TI - SU-D-211-03: An Automated Inverse Planning Optimization Approach for Single-
Fraction and Fractionated Radiosurgery Using Gamma Knife Perfexion.
AB - PURPOSE: The purpose of this work is to develop an automated inverse planning
approach to generate singe-fraction and fractionated stereotactic radiosurgery
(SRS) treatment plans for Gamma Knife Perfexion. METHODS: Our automated approach
consists of two steps: 1) a grassfire-based algorithm to carefully determine the
isocentre locations; 2) a penalty-based optimization to find the optimal shot
shapes and their intensities to minimize the deviation of the delivered dose from
the objective dose in all structures. For single-fraction SRS, a margin-less
approach was taken: conformity of dose to the gross tumor volume (GTV) with a
steep dose fall-off was prioritized. For fractionated radiosurgery, dose
homogeneity was given a higher priority since planning target volumes (PTV) were
applied to account for daily setup variation, and these PTVs could overlap with
organs-at-risk (OARs). The two-step approach was tested on seven clinical cases
with PTV sizes of 0.5cm3-56.5cm3. In the tested cases, the PTV had 0%-38% overlap
with OARs. RESULTS: For single-fraction SRS, the dose to 1mm3 brainstem was on
average 0.24Gy (range: -2.4Gy to +2.0Gy) lower compared to manually-generated
plans. Beam-on time varied with the number of isocentres, but on average was
33min longer than manually- generated plans. The optimization algorithm took
215min on average, while isocentre selection performed in <10s.For fractionated
SRS, the average PTV coverage was V95=94.9% (range: 92.7%-97.6%) and the mean
dose to 1 mm3 brainstem was 87.8% of the prescription dose (range: 35.4%-
108.8%). The mean beam-on time per fraction per dose-per-fraction was 4.8min/Gy
(range: 0.9min/Gy-10.3min/Gy). We observed a tradeoff between conformity and OARs
sparing in both plans, and added sensitivity to isocentre locations in
fractionated plans. In all the cases, GTV received the full prescription dose.
CONCLUSIONS: The results indicated that automated inverse planning yields
improved conformity and OAR-sparing for single- fraction SRS and is capable of
generating homogeneous fractionated SRS. This work is partially funded by Elekta
Instrument, AB, Stockholm, Sweden.
PMID- 28517429
TI - SU-D-217BCD-06: Evaluation of Effective Dose during Neuro 3-D Imaging Using a C
Arm Cone-Beam CT System.
AB - PURPOSE: The purpose of this study was three-fold: 1) to estimate the organ doses
and effective dose (ED) for patients undergoing neuro 3D-imaging protocols, 2) to
study the effect of beam collimation on ED, and 3) to derive protocol-specific
DAP-to-ED conversion factors. METHODS: A cone-beam CT system (Philips Allura Xper
FD20/20) was used to measure the organ doses for seven neuro imaging protocols.
Two data sets were obtained: seven protocols with uncollimated beam (FOV: entire
head) and four with beam collimation (FOV: roughly from the base to the top of
the skull). Measurements were performed on an adult male anthropomorphic phantom
(CIRS, Norfolk, VA) with 20 MOSFET detectors (Best Medical Canada, Ottawa,
Canada) placed in selected organs. The dose area product (DAP) values were
recorded from console. The ED values were computed by multiplying measured organ
doses to corresponding ICRP 103 tissue weighting factors. RESULTS: For seven
protocols with uncollimated setting, the EDs ranged from 0.16 mSv to 1.6 mSv, and
the DAP-to-ED conversion factors range from 0.037 to 0.17 mSv/Gy/cm2 . For four
protocols with beam collimation, the ED was reduced approximately by a factor of
2, and the DAP-to-ED conversion factors by approximately 30%. CONCLUSIONS: We
have measured ED for standard adult neuro imaging protocols in a 3-D rotational
angiography system. Our results provide a simple means of ED estimation using DAP
values from console in the C-arm cone-beam CT system. Research was funded in part
by Philips Healthcare, the Netherlands.
PMID- 28517430
TI - SU-D-BRCD-02: A Novel Cylindrical 3D Water Scanner for Beam Data Collection: I.
Validation of the Automatic-Setup.
AB - PURPOSE: To determine the accuracy and reproducibility of the automatic- setup
procedure of a 3D water scanner (3D SCANNER, Sun Nuclear Corp). The procedure
automatically aligns the scanner's coordinate system to the Linac coordinate
system. A unique off-center detector holder extends the scan range to 630 mm,
eliminating the need for scanner shifts for large-field scans. METHODS: The
automatic-setup procedure provides means to automatically (1) level the tank; (2)
zero the detector position to water surface; (3) align the scanner's coordinate
system to the Linac system; and (4) correct motor hysteresis. After automatic
setup, (1) and (2) were evaluated visually by three physicists. Step (3) was
tested by moving one of the jaws to the isocenter and scans were made along the
jaw edge. Angular misalignment between the scanner and the Linac would Result in
a noticeably tilted profile. Step (4) was tested by scanning with the chamber
moving forward and then backward five times. The accuracy of the off-center
detector holder was tested by comparing scans made using the regularand the off
center detector holders. All tests were repeated three times. RESULTS: All tests
of the water surface and horizontal chamber movementwere acceptable from the nine
independent evaluations. Scans along the jawedge resulted in < 1% in profile
tilt, corresponding to < 0.05 degree in angular misalignment. Same direction
scans resulted in field edge differences < 0.05 mm, and < 0.2 mm when compared to
scans in thereverse direction. There was no difference in accuracy when different
scan speeds were used. Profiles obtained using the regular and the off
centerdetector holders were identical. CONCLUSIONS: The automatic-setupprocedure
resulted in accurate alignment of the 3D SCANNER to the Linac. These results were
user-independent. It also provides the ability to scan large fields without the
need to change tank setup. This work was partially supported by a research grant
from Sun Nuclear Corp., Melbourne, FL.
PMID- 28517431
TI - SU-D-BRA-01: Accurate Real-Time Tumor Motion Estimation from Respiratory
Surrogates via Memory-Based Learning.
AB - PURPOSE: Respiratory tumor motion is a major challenge in radiation therapy.
Effective beam gating or tracking approaches necessitate an accurate knowledge of
the real-time tumor motion. Fluoroscopic tracking with implanted fiducial markers
is invasive and exposes the patient to additional imaging dose. Respiratory
surrogate signal measured by external noninvasive and non-ionizing devices
provides an attractive approach, in which estimating the tumor motion from
respiratory surrogates is crucial. METHODS: We utilize a powerful memory-based
learning approach to find the complex relations between tumor motion and
respiratory surrogates. The learning method uses locally weighted functions to
interpolate between and extrapolate from training data. Due to the local nature
of the learning functions, it is inherently robust to outliers. Moreover, both
training and adapting to new data is highly efficient and almost free, making it
suitable for dynamically following possibly variable internal/external relations.
We evaluated the method using respiratory motion data (3D tumor motion plus 1D
surrogate) from six patients (three lung and three pancreas patients). RESULTS:
Given only 5-sec (roughly one breath) pretreatment training data, the method
achieved an average 3D error of 0.37 mm (range: 0.10 mm - 1.06 mm) and 95th
percentile error of 0.86 mm (range: 0.24 mm - 2.47 mm) on 120-sec unseen test
data. These errors are well below the average peak- to-peak amplitude (-10 mm).
The errors decrease monotonically with an increasing amount of training data.
Compared with the best linear model, the learning approach achieved a 21%
reduction in error for an average patient (range: 10% - 42%). CONCLUSIONS: The
memory-based learning technique is able to accurately capture the highly
nonlinear and complex relations between tumor and surrogate motion in an
efficient manner (~1 ms per prediction). These desirable properties make it an
ideal candidate for accurate and robust tumor gating/tracking using respiratory
surrogates.
PMID- 28517433
TI - SU-E-T-441: A Feasibility Study to Replace Electron Cutouts with a Motorized
Electron Multileaf Collimator.
AB - PURPOSE: Fabrication of electron beam cutouts not only is a time consuming
process but also involves the handling of cerrobend which is a toxic material.
Hospital workers involved in cutout construction can actually be exposed to toxic
fumes that are usually generated during the process. The aim of this work is to
study the feasibility of replacing electron cutouts with our prototype motorized
electron multileaf collimator (eMLC). METHODS: Electron beams collimated by an
eMLC have very similar penumbra to those collimated by applicators and cutouts as
we already demonstrated in a previous study. However undulation of the isodose
curves is expected due to the finite size of the eMLC. This may be a problem when
the field edge is close to critical structure. Thus ten different breast cases
that were previously treated with an electron boost were selected from our
database. An inhouse Monte Carlo based treatment planning system were used for
dose calculation using the patients CTs. For each patient two plans were
generated one with electron beams collimated using the applicator/cutout
combination and the other plan with beams collimated only by the eMLC. Treatment
plan quality was compared for each patient based on dose distribution and dose
volume histogram. In order to determine the optimal position of the leaves, the
impact of the different leaf positioning strategies were investigated. RESULTS:
Results have shown that target coverage and critical structure sparing can be
effectively achieved by electron beams collimated by eMLC. Preliminary results
have shown that the out-of-field strategy is most conservative and would be the
recommended method to define the actual leaf position for the eMLC defined field.
CONCLUSION: The eMLC represents an effective time saving and pollution free
device that can completely eliminate the need for patient specific cutouts. This
work has been supported by a UICC American Cancer Society Beginning Investigators
Fellowship funded by the American Cancer Society.
PMID- 28517432
TI - Newborn screening for PIDs using both TREC and KREC identifies late occurrence of
B cells.
PMID- 28517434
TI - SU-E-T-481: Dosimetric Effects of Tissue Heterogeneity in Proton Therapy: Monte
Carlo Simulation and Experimental Study Using Animal Tissue Phantoms.
AB - PURPOSE: Accurate determination of proton dosimetric effect for tissue
heterogeneity is critical in proton therapy. Proton beams have finite range and
consequently tissue heterogeneity plays a more critical role in proton therapy.
The purpose of this study is to investigate the tissue heterogeneity effect in
proton dosimetry based on anatomical-based Monte Carlo simulation using animal
tissues. METHODS: Animal tissues including a pig head and beef bulk were used in
this study. Both pig head and beef were scanned using a GE CT scanner with 1.25
mm slice thickness. A treatment plan was created, using the CMS XiO treatment
planning system (TPS) with a single proton spread-out-Bragg-peak beam (SOBP).
Radiochromic films were placed at the distal falloff region. Image guidance was
used to align the phantom before proton beams were delivered according to the
treatment plan. The same two CT sets were converted to Monte Carlo simulation
model. The Monte Carlo simulated dose calculations with/without tissue omposition
were compared to TPS calculations and measurements. RESULTS: Based on the
preliminary comparison, at the center of SOBP plane, the Monte Carlo simulation
dose without tissue composition agreed generally well with TPS calculation. In
the distal falloff region, the dose difference was large, and about 2 mm isodose
line shift was observed with the consideration of tissue composition. The
detailed comparison of dose distributions between Monte Carlo simulation, TPS
calculations and measurements is underway. CONCLUSIONS: Accurate proton dose
calculations are challenging in proton treatment planning for heterogeneous
tissues. Tissue heterogeneity and tissue composition may lead to isodose line
shifts up to a few millimeters in the distal falloff region. By simulating
detailed particle transport and energy deposition, Monte Carlo simulations
provide a verification method in proton dose calculation where inhomogeneous
tissues are present.
PMID- 28517435
TI - SU-E-T-452: Impact of Abdominal Compression on the Tumor Motion in the Treatment
of NSCLC Using Stereotactic Body Radiosurgery.
AB - PURPOSE: Involuntary motion of the tumor during the treatment of NSCLC using
stereotactic body radiosurgery presents its own unique challenges. In this study,
we quantify the impact of abdominal compression technique to minimize tumor
motion as a function of location of tumor in a patient. METHODS: 25 patients (5
in each lung lobe viz. RUL, RML, RLL, LUL and LLL) were retrospectively analyzed.
A 4DCT study encompassing the tumor was used on a 16 slice GE CT scanner along
with Varian RPM gating system. The images were retrospectively binned in 10
phases. The motion of tumor was analyzed phase by phase in transverse, sagittal &
coronal projections of the 3D image. This gave us 2 values for anterior
posterior, superior-inferior and lateral-medial motions each and was averaged
out. RESULTS: Analysis of data reveals that the motion (mean +/- 1SD) in the
superior-inferior direction was 1.8 +/- 0.9, 4.2+/-2.8, 7.4+/-2.3, 1.5+/-0.8,
3.1+/-2.8 mm for tumors located in RUL, RML, RLL, LUL and LLL, respectively.
Along the anterior-posterior direction the respective values were 2.5 +/- 1.9,
2.4 +/- 1.1, 2.7 +/- 1.3, 1.4 +/- 0.2 and 1.8 +/- 1 mm. Similarly, along the
lateral direction, the respective values were 2.1 +/- 1.1, 1.9 +/- 1.1, 1.6 +/-
1.3, 1.1 +/- 0.3 and 1.8 +/- 0.7 mm. When the data was analyzed removing the
location of the tumor in the thorax, the median displacement along the superior
inferior, anterior-posterior, lateral direction was 2.3, 1.6 and 1.5 mm,
respectively while the respective maximum value were 9.2, 5 & 3.8 mm.
CONCLUSIONS: The use of abdominal compression provides a simple inexpensive yet
easily tolerable device to control the motion of the tumor in the management of
NSCLC for SBRT treatments. This will allows the treatment of the tumor without
resorting to complex and time consuming gated treatments.
PMID- 28517436
TI - SU-E-T-492: The Dosimetric and Clinical Impact of the Metallic Dental Implants on
Radiation Dose Distributions in IMRT Head and Neck Cancer Patients.
AB - PURPOSE: In H&N cancer patients, the development of oral mucositis is related
closely to the radiation dose to the oral cavity. It is generally presumed that
the existence of metallic dental implants makes it worse due to the scattering
effect of the metal. This study investigates the effects of the dental implants
on radiation doses to PTV, tongue mucosa, and other structures for IMRT H&N
cancer patients by Monte Carlo (MC) dose calculations. METHODS: Two H&N cancer
patients who have dental implant and are treated by IMRT technique are selected
for the purpose. The BEAMnrc/DOSXYZnrc MC codes are employed for the CT-image
based dose calculations. The radiation sources are the validated Varian phase
space files for 6MV linac beams. The CT image artifacts caused by the dental
fillings are replaced by tissue material. Two sets of MC calculations for each
patient are performed at a calculation statistics of 1%: one treats all dental
implants as bones, the other substitutes the implants by metal of either titanium
or gold with correct density. Doses in PTV and various tissue structures are
compared for the two scenarios. RESULTS: With titanium implant, there is no
significant difference in doses to PTV and tongue mucosa from that when treating
implant as bone. With gold implant, the mean dose to PTV is slightly lowered by
1%; the mean dose to tongue mucosa is reduced by less than 0.5%, although the
maximum dose is increased by 5%. CONCLUSIONS: The scattering dose from titanium
implants is not of concern for H&N patients irradiated by 6MV IMRT beams. For
gold implants, the scattering dose to tongue mucosa is not as severe as presumed;
and the dose to PTV could be slightly compromised due to the attenuation effect
of the metal. This work was supported in part by Varian Medical Systems.
PMID- 28517437
TI - SU-E-T-463: Biological-Based Optimization and VMAT is Unnecessary for
Stereotactic Body Radiation Therapy.
AB - PURPOSE: This study shows that there is no clear dosimetric benefit of biological
based optimization for either fixed-beam IMRT or VMAT. Other than shorter
delivery times, even VMAT does not offer additional advantage to fixed-beam IMRT.
METHODS: A small number of patients for lung, pancreas, spine and brain CA were
planned with fixed-beam IMRT, optimized with (gEUD) and without (DV) biological
objectives and, also planned for VMAT with and without gEUD, for comparison. For
the lung and brain cases, a non-coplanar 7-11 beam arrangement was used for fixed
beam IMRT and a coplanar 'hybrid' arc simulated VMAT with beams set every 5
degrees spacing. For the other treatment sites, all beams were coplanar. For
each case, the fixed-beam IMRT and VMAT plans were optimized with the same
objectives. It is important to note that, only 2 segments/beam were allowed for
each plan, in order to create small fluence modulation, appropriate for small
target volumes during SBRT. RESULTS: For all plans we noticed that there were
minor or no dosimetric differences between fixed- beam IMRT and VMAT, whether DV
or gEUD objectives were used or whether fixed-beam IMRT or VMAT is used. Keeping
the level of beam modulation as-low-as possible, for small SBRT targets, one can
show that VMAT with or without gEUD optimization does not offer any dosimetric
advantage against fixed-beam IMRT with multiple non-coplanar beams. This is
against the expectation that gEUD-optimization can Result superior plans than DV
optimization. The difference is that, for small target volumes like those
encountered in SBRT, the complexity of the fluence is not as high as in large
field intensity modulated cases. CONCLUSIONS: The fact that VMAT with or without
gEUD can produce as good plans as fixed-IMRT does not make VMAT a preferred
treatment modality, other than the fact that requires reduced treatment time.
PMID- 28517438
TI - SU-E-T-474: Monte Carlo Phase Space Production to Model Magnetically Scanned
Proton Beams for IMPT.
AB - PURPOSE: Accurate dose predictions in proton beam therapy using magnetically
scanned beams are highly dependent on the accurate modeling of the lateral dose
profiles. This study was performed to provide proton phase spaces for Monte Carlo
simulations, used to accurately simulate doses at distances up to 12 cm from the
central axis of the beam. METHODS: Measured lateral dose profiles at various
depths in water were compared to Monte Carlo simulations of doses for 90 discreet
initial proton energies. Phase spaces were produced using a one dimensional
energy distribution, and a combination of several two dimensional spatial and
directional distributions. Simulations were performed iteratively using
variations in the initial phase space distributions to achieve acceptable
agreement between measured and simulated lateral dose profiles, i.e. differences
in FWHM < 0.5 mm and dose differences less that 0.1% at distances up to 12.5 cm.
RESULTS: 90 phase spaces of proton sources for different initial beam energies
were created for use in Monte Carlo simulations of scanned proton beam therapy
patient plans. At a depth of 2 cm in water, the simulated and measured FWHM of
the lateral dose profiles differed in in-plane direction by an average of 0.05
mm, in cross-plane direction by 0.13 mm. All simulated profiles were within 0.1%
of the measured doses at distances between 2cm and 12.5 cm from the central beam
axis. CONCLUSIONS: A library of 90 phase space files has been created to
accurately simulate magnetically scanned proton beams for IMPT, providing
accurate dose distributions up to 12 cm distance from the central beam axis. This
project is supported in part by P01CA021239 from the National Cancer Institute.
The content is solely the responsibility of the authors and does not necessarily
represent the official views of the National Cancer Institute or the National
Institutes of Health.
PMID- 28517439
TI - SU-E-T-445: A Dosimetric Comparison of Gamma Knife Plans with Measurement Based
and Image Based Skull Definitions.
AB - PURPOSE: To compare gamma knife treatment plans that use skull scaling instrument
measurements for skull definition vs. CT based skull definition. METHODS: Eight
previously treated patients who had head CT scans were randomly selected. Their
CT images were imported into Leksell GammaPlan. For each patient, three dose
plans were developed: 1. the reference plan. It was planned based on the standard
clinical treatment planning guidelines. Measurements were used for skull
definition and TMR10 for dose calculation algorithm. 2. CT TMR10 plan, a
recalculation of the reference plan with CT images used for skull definition 3.
CT Convolution plan, a recalculation of the TMR10 plan using convolution
algorithm. The treatment times for CT TMR10 plan and CT convolution plan were set
to be the same as the reference plan by adjusting the prescription dose level.
Prescription dose and shots were left unchanged. Plan comparisons were carried
out using minimum dose, target coverage, gradient index and selectivity. RESULTS:
On average, the minimum dose for CT TMR10 and CT Convolution plans are 1.8% and
6.5% lower than that of the reference plan. The target coverage, gradient index
are comparable for these three plans. The selectivity indices for CT TMR10 and CT
Convolution plans were found to be 3.1% and 9.8% higher than that of reference
plan. CONCLUSIONS: This work indicates the measurement based skull definition
could Result in inaccurate calculation in minimum dose to the target. The target
coverage and gradient index are however uncompromised. The selectivity index was
actually underestimated.
PMID- 28517440
TI - SU-E-T-485: Validation of Acuros XB Dose Calculations in SBRT Lung Planning with
Monte Carlo Methods.
AB - PURPOSE: The Acuros XB (AXB) Advanced Dose algorithm (Varian Medical Systems)
represents a dramatic shift in clinical photon dose calculation methodology from
pencil-beam superposition/convolution methods. Early studies evaluating the
accuracy of the algorithm in lung have found good agreement with both measurement
and Monte Carlo based dose calculations. In this study, a dosimetric validation
of Acuros is performed for clinical SBRT lung planning cases using Monte Carlo
(MC) calculations as a benchmark. METHODS: MC simulations using BEAMnrc/DOSXYZnrc
were carried out for 8 AXB calculated 6/10 MV arc plans delivered on a TrueBeamTM
STx linac in high-dose-rate flattening filter free mode. Clinical planning
constraints were applied in each case with plans normalized to achieve 95% PTV
coverage. Metrics used in the evaluation include: maximum and minimum GTV/PTV
dose, PTV isodose coverage, conformity and dose profile comparisons. To
understand the impact of moving toward to AXB calculations in SBRT lung planning,
calculations using the Analytical Anisotropic Algorithm (AAA) are presented for
each plan. RESULTS: For both 6 and 10MV energies, consistent mean GTV dose and
PTV isodose coverage was observed for AXB and MC calculations. GTV mean dose was
observed to deviate by <2% for all cases. Isodose coverage for MC simulations
ranged from 92%-98%. AAA was also in agreement with MC simulations within the GTV
to within 2%. AXB and MC maximum and minimum PTV dose differences were larger (up
to 9%) but not of clinical concern. In several cases, AXB exhibited a significant
improvement in dose calculation accuracy in the lung region surrounding the GTV
over AAA, particularly with lung densities < 0.1 g/cc. CONCLUSION: AcurosXB
provides increased accuracy in modelling dose deposition for SBRT lung over AAA
and is found to be in good agreement with MC calculations.
PMID- 28517441
TI - SU-E-T-456: Potential Optimization of Stereotactic Body Radation Therapy (SBRT)
from a Simple Field Timing Rearrangement.
AB - PURPOSE: Stereotactic Body Radiation Therapy (SBRT) is a radiotherapy technique
which uses high dose fractions with multiple coplanar and non- coplanar beams.
Treatments are typically protracted with more fields than conventional radiation
treatment schemes. The timing of field delivery may have an impact on the
radiobiological results for SBRT. METHODS: In a cohort of eight SBRT patient
treatments, the protraction factor (G-value), LPL, and LQL models were used to
optimize field arrangements. An actual field timing delivered in the clinic (C)
was included for comparison. The LPL model was used to quantify the difference in
survival fractions (SF). Published data from three cell lines for non-small cell
lung cancers: H460, H660, and H157 was used to acquire the model parameters. The
results were displayed as (C:O)N or (V:O)N, where C, V, and O were the SF for the
clinical (C), least favorable (V), and optimal (O) field timings respectively. N
represents the number of fractions for the SBRT protocol. RESULTS: Results from
all three models indicate that the optimal field order occurs when the fields are
arranged in a triangle like pattern, where the highest dose fields are positioned
centrally. Minimization of cell kill was achieved with a V-shaped orientation,
although these results were not as conclusive. Results of the SF ratios
demonstrated that regardless the cell type and model the triangle shape had lower
cell survival fractions compared to both the C and the V arrangement. For
example, the H460, with repair half-time = 1.50 h, an average ratio of (C:O)3 =
5.8, suggesting the triangle pattern is approximately 6 times more effective than
the clinical plan, after 3 fractions. CONCLUSIONS: Rearranging field timing for a
SBRT treatment so that maximal dose is deposited in the central fields of
treatment may optimize cell kill and potentially affect overall treatment
outcome.
PMID- 28517442
TI - SU-E-T-496: Monte Carlo Simulation of a 6MV Varian Truebeam Without Flattening
Filter Linac.
AB - PURPOSE: To simulate a 6 MV Varian Truebeam linac operating without flattening
filter using an existing Phase space file(PhS) with the monte carlo packeage
EGSnrc. METHODS: An existing PhS file built after simulating the patient
independent part at the first step in traditional monte carlo simulation was
employed. With this PhS being a source, the patient-dependent part was simulated
and the dose distributions were calculated using EGSnrc. The 6 MV dose
calculation were performed for field size of 10*10cm2 , 20*20cm2 , 30*30cm2 and
40*40cm2 in a 54*54*30 cm3 water phantom. The voxel size for the water phantom
was 0.6*0.6*0.6cm3 . For the 10*10cm2 field, surface buildup calculations were
performed using 0.6*0.6*0.3cm3 voxels within 1.8cm of the surface. Dose profiles
and percent depth dose(PDD) curves were calculated following 1 billion histories
for dose profiles and 500 million histories for PDD curves. Simulation results
were compared with measured data for validation. RESULTS: Good agreement between
simulations and measurements in water was observed. For the PDD curves, 95% of
the calculated data points agree within 2% with the experimental measurements for
depths between 1.8cm and 30 cm. In the buildup region, the agreement is within
2%, except several points with the deviation of 5% for the 10*10 cm2 open field.
For the lateral dose profiles, the agreement is less than 3% at the depth of
1.3cm, 5cm, 10cm, 20cm and 30cm inside the 80% field size. CONCLUSIONS: It
demonstrated that the existing phase space file is accurate and the simulation is
reliable to be used for clinical patient dose calculations in future
investigations. Project supported by the National Natural Science Foundation of
China (30970866).
PMID- 28517443
TI - SU-E-T-467: Monte Carlo Dosimetric Study of the New Flexisource Co-60 High Dose
Rate Source.
AB - PURPOSE: Recently, a new HDR 60Co brachytherapy source, Flexisource Co-60, has
been developed (Nucletron B.V.). This study aims to obtain quality dosimetric
data for this source for its use in clinical practice as required by AAPM and
ESTRO. METHODS: Penelope2008 and GEANT4 Monte Carlo codes were used to
dosimetrically characterize this source. Water composition and mass density was
that recommended by AAPM. Due to the high energy of the 60Co, dose for small
distances cannot be approximated by collisional kerma. Therefore, we have
considered absorbed dose to water for r<0.75 cm and collisional kerma from
0.75 0.8 cm
and up to 2% closer to the source. Using Penelope2008 and GEANT4, an average of
I> = 1.085+/-0.003 cGy/(h U) (with k = 1, Type A uncertainties) was obtained.
Dose rate constant, radial dose function and anisotropy functions for the
Flexisource Co-60 are compared with published data for other Co-60 sources.
CONCLUSIONS: Dosimetric data are provided for the new Flexisource Co-60 source
not studied previously in the literature. Using the data provided by this study
in the treatment planning systems, it can be used in clinical practice. This
project has been funded by Nucletron BV.
PMID- 28517444
TI - SU-E-T-478: Geometrical Splitting Technique to Improve the Computational
Efficiency in Monte Carlo Calculations for Proton Therapy.
AB - PURPOSE: To implement a geometry based particle splitting technique in order to
reduce the computation time when generating treatment head phase space files for
proton therapy dose calculations using Monte Carlo (MC) calculations and to
validate the doses generated from these phase spaces with respect to reference
simulations. METHODS: The treatment nozzles at the Francis H Burr Proton Therapy
Center (FHBPTC) were modeled with a new MC tool ('TOPAS' based on Geant4). For
variance reduction purposes, two particle-splitting planes were implemented, one
downstream of the second ionization chamber the other upstream of the aperture of
the nozzle and phase spaces in IAEA format were recovered. The symmetry of the
proton beam was considered to split the particles by a factor of 4 per plane.
Split particles were randomly positioned at different locations rotated around
the beam axis. The computational efficiency was calculated and dose profiles
compared for a voxelized water phantom for different treatment fields for both
the reference and optimized simulations. Depth-dose curves and beam profiles were
analyzed. Dose calculation in patients was simulated to compare the performance.
RESULTS: Normalized computational efficiency between 10 and 14.5 were reached.
Percentage difference between dose profiles in water for simulations done with
and without particle splitting is within the statistical precision of 2%, 1
standard deviation. Dose distributions for the realistic patient treatment show
differences up to 4% in the regions of interest, within 2 standard deviations.
CONCLUSIONS: By considering the cylindrically symmetric region of the nozzle and
the splitting planes separated at strategic distance, considerable time reduction
can be achieved without compromising the precision. This approach will reduce the
time for phase space simulations for clinical MC dose calculation at FHBPTC by
more than a factor of 10.
PMID- 28517445
TI - SU-E-T-449: Dosimetric Comparison of Beam Arrangements for Stereotactic Body
Radiotherapy of Lung Lesion.
AB - PURPOSE: Dosimetric comparison of beam arrangements of coplanar, non- coplanar
and conformal arc for Stereotactic body radiotherapy of lung lesion. METHODS:
Four spherical targets with diameters of 2, 4, 6 and 7cm are contoured in the
geometric center of right lung of a selected SBRT CT scan. For each target,
treatment plans of optimized 7, 9 and 11 coplanar, non- coplanar and conformal
arc beam arrangements are generated in Pinnacle (Pinnacle Version 9.0, Philips
Radiation Oncology Systems, WI). Prescription isodoses are chosen to cover at
least 95% of target volumes. The volumes enclosed by the prescription and 50% of
prescription isodose surfaces are computed. Conformality index (CI) and effective
dose fall off gradient are computed for dosimetric comparison. RESULTS: All plans
with optimized coplanar and conformal arc beam arrangements have similar CIs
while optimized non-coplanar beam arrangements have the smallest CIs. For each
target size, optimized 7 and 9 coplanar beam arrangements have the largest half
prescription isodose volumes while optimized 11 coplanar beam arrangements have
slightly less half prescription isodose volumes than conformal arc plans. All 3
optimized non-coplanar beam arrangements Result in faster dose gradient than
conformal arcs except for the smallest target cases, for a 2cm diameter target, 9
or 11 non-coplanar beams are needed to achieve better dose gradient than their
rival conformal arc plan. CONCLUSIONS: Treatment plans using optimized 9 and 11
non-coplanar beam arrangements are superior to conformal arc plans for SBRT of
lung lesions based on dosimetric comparison. To achieve a superior plan for small
lesions, 11 or more optimized coplanar beams may be required.
PMID- 28517446
TI - SU-E-T-489: Quantum versus Classical Trajectory Monte Carlo Simulations of Low
Energy Electron Transport.
AB - PURPOSE: Widely-used classical trajectory Monte Carlo simulations of low energy
electron transport neglect the quantum nature of electrons; however, at sub-1 keV
energies quantum effects have the potential to become significant. This work
compares quantum and classical simulations within a simplified model of electron
transport in water. METHODS: Electron transport is modeled in water droplets
using quantum mechanical (QM) and classical trajectory Monte Carlo (MC) methods.
Water droplets are modeled as collections of point scatterers representing water
molecules from which electrons may be isotropically scattered. The role of
inelastic scattering is investigated by introducing absorption. QM calculations
involve numerically solving a system of coupled equations for the electron
wavefield incident on each scatterer. A minimum distance between scatterers is
introduced to approximate structured water. The average QM water droplet
incoherent cross section is compared with the MC cross section; a relative error
(RE) on the MC results is computed. RESULTS: RE varies with electron energy,
average and minimum distances between scatterers, and scattering amplitude. The
mean free path is generally the relevant length scale for estimating RE. The
introduction of a minimum distance between scatterers increases RE substantially
(factors of 5 to 10), suggesting that the structure of water must be modeled for
accurate simulations. Inelastic scattering does not improve agreement between QM
and MC simulations: for the same magnitude of elastic scattering, the
introduction of inelastic scattering increases RE. Droplet cross sections are
sensitive to droplet size and shape; considerable variations in RE are observed
with changing droplet size and shape. CONCLUSIONS: At sub-1 keV energies, quantum
effects may become non-negligible for electron transport in condensed media.
Electron transport is strongly affected by the structure of the medium. Inelastic
scatter does not improve agreement between QM and MC simulations of low energy
electron transport in condensed media.
PMID- 28517447
TI - SU-E-T-460: Isoeffective Dose Display (EQD2) for Composite Plan of Radiosurgery
and Conventional 3D Radiotherapy.
AB - PURPOSE: Direct addition of doses between plans with different fractionation
fails to provide accurate dose-response information to anticipate clinical
outcome. To combine different fractionation patterns, first-order biological
model correction for dose-rate must be included. Moreover, 3-D isoeffect patterns
of the combined doses must be displayed so that overlap area to elegant volumes
can be avoided. The linear quadratic (LQ) model and biologically effective dose
(BED) method were used to produce a combined plan in equivalent 2 Gy fractions
(EQD2) for radiosurgery and conventional 3D radiotherapy. METHODS: For patients
with multiple courses of radiotherapy, dose distributions of the prior and boost
treatment plans were converted to BED. The fraction size specified by the
prescription was applied globally for each BED calculation, alpha/beta ratio of
10 and 2.5 was used for early and late effect, respectively. Image registration
with CT or MR was performed for initial and boost plans. The registration
information was applied to dose distributions to obtain the composite EQD2.
RESULTS: As a demonstration of this method, two patients were selected who had
combined treatments from substantially different modalities. A patient with liver
cancer initially received radiotherapy of 30 Gy/10 Fx and re-irradiation with
CyberKnife radiosurgery (15 Gy/1 Fx). The combined plan showed that the PTV
received EQD2 of 63.8 Gy. Another patient had brain metastasis treated with
GammaKnife of 18 Gy (50% isodose) followed by conventional 3D whole brain
radiation of 30 Gy/10 Fx. The minimal combined tumor EQD2 was 74.5 Gy. Early and
late calculated responses showed that all critical organ doses were within
tolerance. CONCLUSIONS: For patients receiving radiation with different
fractionation schemes, combined isoeffective dose distributions were calculated
and displayed. In both cases, crucial information regarding 3-D dose
distributions assisted the physicians in determining whether tolerance limits of
overlap areas of retreated critical structures were preserved.
PMID- 28517448
TI - SU-E-T-451: Optimization of Normalized Prescription Isodose Selection for
Stereotactic Radiation Therapy: Conventional Vs. Robotic Linac.
AB - PURPOSE: To determine the optimal prescription isodose line that minimizes normal
tissue irradiation for stereotactic radiation therapy comparing conventional
linear accelerator and robotic delivery. METHODS: A computer based digital torso
phantom which has the capability to simulate respiratory and cardiac motion were
used in this study. Spherical targets were constructed in lung and liver, with
diameter of 20mm, 30mm, and 40mm. Two concentric 5mm shells, from the target
surface extending 5mm radially and from 5mm to 10mm, were identified/contoured.
Non-coplanar, non- opposing 3D conformal beams were designed for linac planning.
Variable prescription isodose lines were achieved by varying the block margin. 4D
dose calculation was used for moving target and surrounding tissue. After linac
planning, the CT images and contours were transferred for Cyberknife(r) planning.
Variable prescription isodose lines were achieved by inverse planning technique.
Doses of 60Gy in 3 fractions were prescribed to cover exactly 95% of target tumor
with each technology. gEUD (generalized effective uniform dose) with different
formulations for parallel and serial tissues was used for comparison between
different plans. RESULTS: For linac plans, the optimal prescription isodose line
yielding maximum normal tissue sparing occurs between 50% and 70% for the lung
tumor and 60% and 90% for liver tumor. The gEUD difference between plans with
optimum and arbitrarily chosen prescription isodose line may be up to 20% of
prescription dose. For Cyberknife plans, the optimal prescription isodose line is
approximately 50% for tissues displaying either parallel or serial behavior.
These results are similar for different tumor sizes. CONCLUSIONS: Both
conventional linac and Cyberknife(r) delivery can provide conformal tumor
coverage with normal tissue sparing. By carefully choosing the optimal
prescription isodose line, the gEUD of the surrounding normal tissue can be
reduced by up to 20% of prescription dose.
PMID- 28517449
TI - SU-E-T-491: A FLUKA Monte Carlo Computational Model of a Scanning Proton Beam
Therapy Nozzle at IU Proton Therapy Center.
AB - PURPOSE: Charged particle therapy, especially proton therapy is a growing
treatment modality worldwide. Monte Carlo (MC) simulation of the interactions of
proton beam with equipment, devices and patient is a highly efficient tool that
can substitute measurements for complex and unrealistic experiments. The purpose
of this study is to design a MC model of a treatment nozzle to characterize the
proton scanning beam and commissioning the model for the Indiana University
Health Proton Therapy Center (IUHPTC. METHODS: The general purpose Monte Carlo
code FLUKA was used for simulation of the proton beam passage through the
elements of the treatment nozzle design. The geometry of the nozzle was extracted
from the design blueprints. The initial parameters for beam simulation were
determined from calculations of beam optics design to derive a semi-empirical
model to describe the initial parameters of the beam entering the nozzle. The
lateral fluence and energy distribution of the beam entering the nozzle is
defined as a function of the requested range. The uniform scanning model at the
IUHPTC is implemented. The results of simulation with the beam and nozzle model
are compared and verified with measurements. RESULTS: The lateral particle
distribution and energy spectra of the proton beam entering the nozzle were
compared with measurements in the interval of energies from 70 MeV to 204.8 MeV.
The accuracy of the description of the proton beam by MC simulation is better
than 2% compared with measurements, providing confidence for complex simulation
in phantom and patient dosimetry with the MC simulated nozzle and the uniform
scanning proton beam. CONCLUSIONS: The treatment nozzle and beam model was
accurately implemented in the FLUKA Monte Carlo code and suitable for the
research purpose to simulate the scanning beam at IUHPTC.
PMID- 28517450
TI - SU-E-T-462: Calculation of Prescribed Dose for Permanent Implant with Cs-131
Using LQ Equation including Resensitization.
AB - PURPOSE: To develop a new biological equivalent dose (BED) formulism that
includes repair, repopulation and resensitization (redistribution and
reoxygenation), and can be used to calculate prescribed dose for permanent
implant with Cs-131. METHODS: Because of lack of sufficient clinical data, the
prescribed dose with new isotopes is usually calculated based on BED compared
with other isotopes that have already been used in clinical practice. The current
widely used formulism of BED calculation for permanent implant which was given by
Dale includes cell repair and repopulation but not resensitization.
Resensitization can be included in the extended LQ equation (LQR) proposed by
Brenner. Applying Dales formulism to Brenners LQR, we obtained a new BED
calculation formula that accounts for resensitization. We used this new formulism
to calculate the BED that corresponds to the prescribed dose for cervix (with Au
198) and prostate (with I-125) permanent implant. Then, we obtained the
prescribed dose with Cs-131 which has the same BED as Au-198 or I-125. RESULTS:
The new formulism was used for prostate and cervix cancer permanent implant. The
prescribed dose with Cs-131 for cervix was 40 Gy (42 Gy without resensitization)
and 66 Gy (69 Gy without resensitization) which were equivalent to 35 Gy and 60
Gy with Au-198, respectively. For prostate implant, the prescribed dose with Cs
131 that corresponded to 144 Gy with I-125 was 135 Gy (124 Gy without
resensitization). CONCLUSION: Resensitization led to significant dose correction
for permanent implant. The calculation of BED and dose was dependent on dose
itself and thus should be patient-specific. Since this calculation relied on many
biological parameters, and may not be accurate if the parameters are not
accurate. Also, the dose prescription should be adjusted based on clinical
outcomes.
PMID- 28517451
TI - SU-E-T-473: Performance Assessment of the TOPAS Tool for Particle Simulation for
Proton Therapy Applications.
AB - PURPOSE: The TOPAS Tool for Particle Simulation was developed to make Geant4
Monte Carlo simulation more readily available for research and clinical
physicists. Before releasing this new tool to the proton therapy community,
several test have been performed to ensure accurate simulations in a variety of
proton therapy setups. METHODS: TOPAS can model a passive scattering or scanning
beam treatment head, model a patient geometry based on CT images, score dose,
fluence, etc., save and replay a phase space, provides advanced graphics, and is
fully four-dimensional (4D) to handle variations in beam delivery and patient
geometry during treatment. An innovative control system meets requirements for
ease of use, reliability and repeatability without sacrificing flexibility. To
test the TOPAS code, we modeled proton therapy treatment examples including the
UCSF eye treatment beamline (UCSFETB), the MGH STAR radiosurgery beamline and the
MGH gantry treatment head in passive scattering and scanning modes. The
simulations included time-dependent geometry and time- dependent beam current
delivery. RESULTS: At the UCSFETB, time- dependent depth dose distributions were
accurately simulated with time- varying energy modulation from a rotating
propeller. At the MGH STAR beamline, distal and proximal ranges agreed within
measurement uncertainty and the shape of the simulated SOBP followed measured
data. For the MGH gantry treatment head in passive scattering mode, SOBPs were
simulated for the full set of range modulator wheel and second scatterer
combinations. TOPAS simulation was within clinical required accuracy. For the MGH
nozzle in scanning mode, a variety of scan patterns were simulated with fluence
maps generated for cases including beam current modulation, energy modulation and
target tracking. CONCLUSIONS: Our results demonstrate the functionality of TOPAS.
They show agreement with measured data and demonstrate the capabilities of TOPAS
in simulating beam delivery in 3D and 4D. This work was supported by IH/NCI under
R01 CA 140735-01.
PMID- 28517452
TI - SU-E-T-444: 4D-CT and Active Breathing Coordinator Play Similar Role in Sparing
Normal Liver Tissue in the Radiotherapy of Hepatocellular Carcinoma.
AB - PURPOSE: To investigate the difference in sparing normal liver tissue between 4D
CT and active breathing coordinator (ABC) in the radiotherapy of Hepatocellular
carcinoma(HCC) applying RapidArc. METHODS: Ten patients with HCC underwent 3D-CT
at end inspiration hold(EIH) associated with active breathing
coordinator(ABC),and 4D-CT scan. The 4D-CT images were sorted in to 10 serious CT
images according respiratory phase. Gross tumor volumes(GTVs) were manually
contoured on different CT images. The individual internal gross target
volume(IGTV) was obtained from 10 GTVs of 4D-CT images. Plan target volumes
(PTVs) were obtained based on IGTV and GTVEIH. PTV1 was obtained from IGTV plus 5
mm margins isotropically, and PTV2 was obtained from GTVEIH using 8 mm margins
isotropically. RapidArc plans were designed on PTV1 and PTV2, for PTV1 RapidArc
plans with one single whole arc were applied and for PTV2 three 135 degrees arcs,
and name RapidArc1 and RapidArc2. Dosimetric differences were compared. RESULTS:
There were no significant difference in conformity index (0.93+/-0.05 Vs 0.93+/
0.03), homogeneity index(1.08+/-0.01 Vs 1.08+/-0.01), the Dl%(54.44+/-0.36 Gy
Vs54.68+/-0.47 Gy) and D99%(49.18+/-0.48Gy Vs 49.00+/-0.34 Gy) between RapidArc1
and RapidArc2(P>0.05). There were no significant differences in the mean
dose(8.23+/-1.5Gy Vs 7.63+/-3.00Gy),V5(46.64+/-19.31Vs43.29+/-19.94), V10(28.73+/
11.54 Vs 28.23+/-12.37), V15(17.87+/-6.61 Vs 18.20+/-7.55), V20(11.62+/-4.39 Vs
11.83+/-4.58), V25(7.71+/-2.91Vs 7.58+/-2.79),V30(5.14+/-2.01Vs5.05+/-1.79),
35(3.41+/-1.35Vs 3.35+/-1.21) and V40(2.12+/-0.86Vs2.06+/-0.75) between RapidArc1
and RapidArc2 (P>0.05). CONCLUSIONS: The RapidArc plans with three 135 degrees
arcs associated could achieve similar dose delivery as the plans with single
whole arc, and 4D-CT and ABC could play similar role in sparing normal liver
tissue assuring the accuracy of target volume in radiotherapy of HCC.
PMID- 28517453
TI - SU-E-T-484: Potential Clinical Impact of Dosimetric Uncertainties in Proton
Therapy.
AB - PURPOSE: The analytical algorithms which are used widely for proton treatment
planning in the current clinical practice may have significant dosimetric
uncertainties in highly heterogeneous regions. The aim of this study is the
assessment of the potential clinical impact of these uncertainties. METHODS: A
cohort of 8 patients with local (in field) recurrences, originally treated for
lung cancer at our institution, was selected for this study. CT scans and
treatment plans were used to assemble the input files for the Monte Carlo (MC)
code MCNPX. The total energy deposition inside the patient volume was computed
with statistical uncertainty of less than 2% and converted to dose-in-water. The
results were compared to the dose computed by the clinical treatment planning
system (TPS). The area of the recurrence was contoured on the follow-up PET/CT
study for each of the patients and registered to the planning CT. RESULTS: While
there is acceptable agreement between the TPS and the Monte Carlo dose in
homogeneous regions, there are noticeable differences caused by heterogeneities.
The regions of largest differences are the points around and beyond the distal
edge and points around the lateral penumbra and in several patients the target
has received lower then the prescribed dose. The area of the recurrence corelates
well with the MC predicted underdosed area of the target. CONCLUSIONS: The
uncertanties in analytical dose algorithms used in clinical TPSs may result in
suboptimal target coverage increasing the possibility of tumor recurrence.
Accurate Monte Carlo simulations can be used to predict and avoid the situations
in which the analytical algorithms have high uncertanties providing for more
robust treatment planning.
PMID- 28517454
TI - SU-E-T-455: Novel Planning Techniques for Lung SBRT.
AB - PURPOSE: Two new planning techniques in lung SBRT are presented. The first
technique involves a differential dosing strategy for patients with compromised
pulmonary function. The second technique compares supine vs prone setup for
extreme posterior lesions. CyberKnifeTM(CK) prone setup is complicated due to
patient discomfort from longer treatment times and the inability to track without
fiducials. METHODS: CK(G.3) MultiplanTM(V3.5). SynchronyTM, XSightTM Lung
Tracking Systems. Our lung SBRT patients are tracked using fiducials with
Synchrony or without fiducials with XSight using a 60 Gy in three fractions
scheme. If the ray-tracing optimized plan results in V15Gy greater than 10% we
employ the differential dosing technique. A new PTV is created to encompass the
54 Gy isodose surface. A more conformal plan with a dose constraint of 60Gy to
CTV and 54Gy to PTV is created appreciably lowering the V15Gy. Alternatively a
54Gy PTV can be created from measured respiration excursions. For the
prone/supine comparison, plans were generated for both positions then evaluated.
RESULTS: Patients planned with the differential dose technique have a good tumor
response as evidenced by a follow-up PET. Although prone setup is preferred for
extremely posterior tumors, a dosimetrically comparable supine plan can be
created to replicate the prone plan. The supine low dose spillage was only
slightly greater than in the prone case. CONCLUSIONS: We conclude that the
54Gy/60Gy dosed patients have almost the same tumor response as the standard 60
Gy treatment. A dosimetrically similar supine plan obviates the need for a prone
delivery.
PMID- 28517455
TI - SU-E-T-495: Monte Carlo Dose Verification of Passive Scattering Proton Therapy
for Prostate Cancer.
AB - PURPOSE: To verify the clinical pencil beam dose calculation algorithm for
passive scattering proton therapy using field with large range in tissue, i.e. in
prostate cancer, using a Monte Carlo (MC) simulation system. METHODS: Previously
treated prostate cancer cases were randomly selected from our patient database.
All patients received the same dose prescription of 50Gy (25 fractions) to
planning treatment volume including the seminal vesicles (PTV1), followed by 28Gy
(14 fractions) boost to the prostate gland only (PTV2). Patient and beam geometry
were imported to our MC simulation platform (TOPAS - TOol for PArticle
Simulation) and the dose of each individual beam, as well as their weighted sum,
were calculated and compared to pencil beam algorithm-based calculation from the
clinical treatment planning system (XiO). RESULTS: Preliminary results from four
patient cases show overall good agreement between the pencil beam and MC
calculations. However, a small but systematic overestimation of the dose, as
calculated by the pencil beam calculation algorithm, was noticed for the target
structures (<2% difference in D95 for PTV1 and PTV2), compared to the MC
calculation. The inverse was observed for the OARs (rectum and bladder) for which
the dose seems to be somewhat underestimated by the pencil beam calculation
algorithm (up to 3.75% difference in the volume covered by the 70Gy and 75Gy
isodose lines). Furthermore, systematic difference in the range calculation was
noticed: the pencil beam calculation algorithm results in larger proton range, in
the order of 3-4mm, compared to the MC calculations for all beams and patients
studied. This can be attributed to the bone anatomy in the path of the beams
(femoral heads). CONCLUSIONS: Routine MC dose calculation has the potential to
improve delivery accuracy in proton therapy of prostate cancer and influence the
analysis of currently ongoing clinical trials of protons versus IMRT. Funded by
NIH/NCI R01 CA140735.
PMID- 28517457
TI - SU-E-T-477: Influence of Eye Size on Radiation Absorbed Dose Delivered to Non-
Targeted Tissues during Stereotactic Radiosurgery for Age-Related Macular
Degeneration.
AB - PURPOSE: This work determines how variations in eye size will influence the
radiation absorbed dose delivered to non-targeted tissues within the eye during
stereotactic radiosurgery of age-related macular degeneration (AMD) using the
IRayTM treatment. METHODS: Stylized models of the eye were created with axial
lengths of 20, 22, 24, 26, and 28mm. Each model was based upon the reference eye
model from NCRP Report 130 and then scaled appropriately for each axial length.
Models were incorporated with MCNPX radiation transport code in order to simulate
the three beam IRayTM delivery system. Simulation results were assessed for both
the mean absorbed dose and dose-volume histograms (DVH) for both target (macula)
and non- targeted eye tissues, including the lens, retina, central retinal
artery, and optic nerve. RESULTS: For each of the three beams, an average dose of
8Gy was delivered to the macula resulting in a total average dose of 24Gy for
each eye model. The lens of the eye received a total average dose ranging from
146 to 189mGy, with the larger doses occurring in the smaller eye models since
the beams traverse through the sciera closer to the limbus. The distal tip
(1.5mm) of the central retinal artery received a total average dose ranging from
499 to 567mGy, with the larger doses occurring in the larger eye models due to
increased scatter resulting from longer tissue path length to the nominal target.
The optic nerve received a total average dose ranging from 207 to 225mGy, with
the larger doses occurring in the smaller eye models. CONCLUSIONS: The small
variation in dose to the lens, central retinal artery, and optic nerve suggests
that eye size does not significantly affect radiation dose to non-targeted eye
tissues. This work was sponsored by Oraya Therapeutics.
PMID- 28517458
TI - SU-E-T-448: Switch Patients between Collimation Systems for CyberKnife Treatment
Feasibility Study.
AB - PURPOSE: There are two collimation systems associated with the CyberKnife system,
the fixed cone collimator and the Iris collimator. The Iris collimator is used
more frequently because of its superior flexibility. However, sometimes
treatments have to be canceled or postponed due to Iris collimator mechanical
failures. The purpose of this study is to investigate the feasibility of
switching collimation systems without replanning. METHODS: We first performed
Monte Carlo simulations on 10 clinical cases using the Iris collimator and the
fixed cone collimator. The conformality index (CI), target volume coverage and
the maximum, minimum and mean doses to the critical structures from the iris and
fixed plans were compared to determine the feasibility of switching between
collimator types without replanning. RESULTS: Our results showed that the two
types of collimators deliver similar dose distributions. The average target doses
for the fixed plans were 1% to 6% higher than those for the Iris plans. The
average CI for the fixed plans was 1.36 compared to 1.28 for the Iris plans.
Thus, we adjusted the Iris sizes with a scale factor of 1.024 to achieve a better
dose match with the fixed collimators. Doses for the 10 cases were then
recalculated. Once this correction was made, the difference between the average
target doses for the two collimator plans was reduced to less than 2% and the CIs
became almost identical. CONCLUSIONS: Small target dose differences were found
between plans using different collimation systems, which may be compensated for
by adjusting the Iris collimator sizes to ensure similar dose distributions. The
differences in the doses to the critical structures between the collimation
systems were insignificant. After adjusting the Iris collimator sizes and re
commissioning the planning system, patients can be safely switched from the Iris
collimator to the fixed cone collimator without replanning.
PMID- 28517456
TI - SU-E-T-466: TCP and NTCP: Is That All?
AB - PURPOSE: Concerns about the secondary cancer risks associated to the peripheral
neutron and photon contamination in photon modern radiotherapy (RT) techniques
(e.g., Intensity Modulated RT -IMRT- or Intensity Modulated Arc Therapy -IMAT)
have been widely raised. Benefits in terms of better tumor coverage have to be
balanced against the drawbacks of poorer organ at risk sparing and secondary
cancer risk in order to make the decision on the optimum treatment technique. The
aim of this study was to develop a tool which estimates treatment success taking
into consideration the neutron secondary cancer probability. METHODS: A
methodology and benchmark dataset for radiotherapy real time assessment of
patient neutron dose and application to a novel digital detector (DD) has been
carried out (submitted to PMB, 2011). Our DD provides real time neutron
equivalent dose distribution in relevant organs along the patient. This
information, together with TCP and NTCP estimated from the DVH of target and
organs at risks, respectively, have been built into a general biological model
which allows us to evaluate the success of the treatments (SA!nchez-Nieto et al.,
ESTRO meeting 2012). This model has been applied to make estimation of treatment
success in a variety of treatment techniques (3DCRT, forward and inverse IMRT,
RapidArc, Volumetric Modulated Arc Therapy and Helical Tomotherapy) to low and
high energy. RESULTS: MU-demanding techniques at high energies were able to
deliver treatment plans with the highest complicated-free tumour control.
Nevertheless, neutron peripheral dose must be taken into consideration as the
associated risk could be of the same order of magnitude than the usually
considered NTCPs. CONCLUSIONS: The methodology developed to provide an online
organ neutron peripheral dose can be successfully combined with biological models
to make predictions on treatment success taking into consideration secondary
cancer risks.
PMID- 28517459
TI - SU-E-T-488: Dose Calculation Model Using the Simplified Monte Carlo Method with
an Initial Beam Model Adapted to a Beam-Wobbling System.
AB - PURPOSE: We have developed an accurate dose calculation model based on a
simplified Monte Carlo (SMC) method adapted to a beam-wobbling delivery system at
National Cancer Center Hospital East (NCCHE). We used an initial beam model
specific to the beam-wobbling system to reproduce accurately different dose
distributions in two lateral directions (x- and y-directions) perpendicular to
each other. METHODS: The SMC calculates a dose distribution by tracking
individual protons. The SMC starts tracking protons at an entrance of a range
compensator. Protons are generated in an initial phase space adapted to the
wobbler system. Since two wobbling-magnets are located at separate places with
different distances from the iso-center, different dose distributions are formed
in x- and y-directions. We derived an initial phase space distribution for the
beam-wobbling system using an analytical method. We used the SMC method with the
initial beam model to calculate dose distributions accurately. To verify accuracy
of the calculation method, we measured the dose distribution in a homogeneous
phantom formed by 235 MeV protons passing through a L-shaped range compensator.
We used a 2D-array of parallel-plate ionization chambers (2D Array seven29(r)) to
measure dose distributions with a sampling period of 5 mm. RESULTS: The measured
dose distribution in the x-direction was different from that in the y-direction.
Our calculation model reproduces the measurement results well in both lateral
directions. In addition, the calculation reproduced the dose increments in edge
regions contributed by edge-scattered protons in collimator. It indicates the
advantage of the SMC. CONCLUSIONS: A dose calculation model has been developed
based on the simplified Monte Carlo method applied to a beam-wobbling system. By
adapting the initial beam model to the wobbling system, the SMC method is found
to reproduce observed different dose distributions in x- and y-directions well.
PMID- 28517460
TI - SU-E-T-459: Radiobiological Evaluation of Implant Duration and Radionuclide
Selection for COMS Eye Plaque Brachytherapy Using an Objective Function.
AB - PURPOSE: The biologically effective dose (BED) of temporary brachytherapy
treatments is a function of both chosen radionuclide (R) and implant duration
(T). This study endeavored to evaluate BED delivered to the tumor volume and
surrounding ocular structures as a function of plaque position (P), prescription
dose, R, and T. METHODS: Plaque-heterogeneity- corrected dose distributions were
generated with MCNP5 for the range of currently-available COMS plaques using low
energy radionuclides. These physical dose distributions were imported into the
Pinnacle3 TPS using the TG-43 hybrid technique and used to generate DVHs for a
T=7d implant within a reference eye geometry at eight standard treatment
positions. The Dale equation was employed to create biologically effective dose
volume histograms (BEDVHs), allowing for BED volumetric analysis of all ROIs.
Isobiologically-effective prescription doses were calculated for T=5-0.01d, with
BEDVHs subsequently generated for all ROIs using correspondingly reduced
prescription doses. Objective functions were created to evaluate the BEDVHs as a
function of R and T. RESULTS: Reducing T from 7 to 0.01d for a 10mm plaque
produced an average BED benefit of 26%, 20%, and 17% for 103 Pd, 125 I, and 131
Cs, respectively, for all P; 16mm and 22mm plaque results were more position
dependent. 103 Pd produced a 16-35% BED benefit over 125 I, whereas 131 Cs
produced a 3-7% BED detriment, independent of P, T, and plaque size.
Additionally, corresponding OAR physical doses were lowest using 103 Pd in all
circumstances. CONCLUSIONS: Shorter implant durations may correlate with more
favorable outcomes vs. 7d implants for small and medium lesions. T may be safely
reduced if the prescription dose is appropriately diminished. 103 Pd offers a
substantial 16- 35% radiobiological benefit over 125 I and 131 Cs irrespective of
P, T, and tumor size. The objective functions used in this study can be applied
to temporary or permanent brachytherapy implants for a variety of disease sites.
PMID- 28517461
TI - SU-E-T-499: Validation of the Varian Generic Phase Space Files for Monte Carlo
Calculations of Dose Distributions for the TrueBeam Linac Head.
AB - PURPOSE: To validate the generic phase space files for Varian TrueBeam linac head
simulations. METHODS: The generic phase space files include the simulation
results of 6MV, 10MV, 6MV FFF, and 10MV FFF (flattening-filter free) operating
modes of TrueBeam for patient-independent linac head components. Using the
generic phase space files as the radiation sources, the BEAMnrc Monte Carlo codes
are used to simulate the patient-dependent parts of the TrueBeam linac and the
resulting phase space files are generated at a plane just before entering a water
phantom for 4 different field sizes (5*5, 10*10, 20*20, and 40*40 cm2 ). Dose
distributions are calculated by DOSXYZnrc in the water phantom of size 50*50*40
cm3 . The percentage-depth-dose (PDD) curves and lateral dose profiles at three
different depths (dmax, 10cm, 20cm) are obtained. Comprehensive comparisons have
been made for a total of 64 dose profiles (including PDDs) between the Monte
Carlo calculations and the measured data. The gamma index analysis is performed
for all the comparisons. RESULTS: The matching of the calculated dose
distributions to the measured ones is analyzed by the gamma index method with a
criterion of 2% dose tolerance and 2 mm distance-to-agreement. Of the 64
comparisons, the minimum gamma index passing rate is at least 92%, after taking
into account the statistical nature of the Monte Carlo calculated dose values.
Despite the existence of latent variance of phase space files, the phantom dose
calculation uncertainty can be less than 1% for field sizes as small as 5*5 cm2 .
The computing time saved by using phase space files could be a factor of 5-10.
CONCLUSIONS: The Varian generic phase space files are accurate and efficient
radiation sources for Monte Carlo calculations of radiation dose distributions
for TrueBeam linac head. This work was supported in part by Varian Medical
Systems and the NIH (1R01 CA104205 and 1R21 CA153587).
PMID- 28517462
TI - SU-E-T-470: Comparison of Proton Treatment Planning and Monte Carlo Calculation
Using TOPAS for Liver Cancer.
AB - PURPOSE: To compare Monte Carlo (MC) calculated and planned dose distributions
(pencil beam algorithm) for patients with liver cancer treated with proton
radiation therapy. METHODS: Six patients with unresectable Hepatocellular
carcinoma were chosen from the institutional protocol list. We applied the newly
developed TOPAS (Tool for Particle Simulation) Monte Carlo (MC) tool and an in
house (mcauto) program, which connects the planning system with the MC. Two
beams, typically right lateral (RL) and anterior-posterior (AP), were simulated
for each patient with a total prescribed dose of 58 Gy. The calculated absolute
dose was determined by separately simulating an SOBP dose in a water phantom for
normalization to the prescription dose. The difference between MC and planned
dose were calculated and Dose Volume Histograms (DVHs) for the critical organs
with non-negligible dose (whole liver, heart, small and large bowel and chest
wall) were analyzed. RESULTS: The resulting dose distributions were in quite good
agreement. The main discrepancy in all cases was observed in the lateral
penumbrae. These discrepancies can mainly result from the range compensator
gradient and tissue composition. The Dose Volume Histograms (DVHs) also presented
good agreement between doses for the CTV as well as all the OARs. The difference
in D95 ranged from 0.7-1.5 Gy that is translated to 1.3-2.5% of the prescribed
dose. CONCLUSIONS: TOPAS Monte Carlo tool presented an efficient and accurate
method for dose calculation in liver and to validate clinical treatment planning.
Discrepancies with doses calculated using the pencil beam algorithm were seen but
were generally quite small.
PMID- 28517463
TI - SU-E-T-461: Fractionation Schedule Optimization for Lung Cancer Treatments Using
Radiobiological and Dose Distribution Characteristics.
AB - PURPOSE: Lung cancer radiotherapy treatments employ a wide variety of
fractionation protocols. The choice among protocols mostly depends on the size of
the target volume (GTV or ITV) and the volume of normal tissue receiving a
critical dose. Rigorous mathematical criteria for normal tissue (NT) dose
distributions were derived to determine the type of dose per fraction schedule
that maximizes linear-quadratic tumor effect. METHODS: Selecting the individual
doses per fraction that maximize a linear-quadratic effect in the tumor while
constraining the normal tissue complication probability according to the Lyman
Kutcher-Burman model leads to an optimization problem. For time-independent
parameters, the solution is always an equal dose per fraction schedule; depending
on parameter values, two different class solutions are suggested: minimal number
of fractions clinically realized with hypo-fractionation, or minimizing dose per
fraction clinically realized with standard- or hyper-fractionation. The value of
a single scale-free "bifurcation" number, derived from the DVH of the NT dose
distribution suggests which solution is preferred for a given plan with respect
to a given normal tissue. The clinical relevance of the bifurcation number in
selecting fractionation schemes was tested for 30 patients previously treated for
non-small-cell lung cancer according to various fractionation protocols. RESULTS:
The bifurcation numbers for both lung and esophagus were a good classifier for
the hypofractionated and the conventional fractionation groups. The variability
of the numbers within patients of the conventional fractionation group was much
smaller than the variability of the treated ITV volumes or the ITV to lung volume
ratios. The prescribed fractionations were also consisted with the currently
accepted alpha-beta values for tumor (10) and radiation-induced pneumonities in
the lung (4). CONCLUSIONS: Model-based criteria such as the bifurcation number
may replace the more empirical volume criteria to decide the optimal
fractionation protocol once the dose distribution has been optimized.
PMID- 28517465
TI - SU-E-T-443: The Dosmetic Difference of RapidArc Plans in Radiotherapy of Multiple
Hepatic Malignancy Applying 6MV and 15MV X-Ray.
AB - PURPOSE: To investigate the dosmetric difference in the application of RapidArc
using 6MV X and 15MVX X-ray for radiotherapy of multiple hepatic malignancy.
METHODS: 12 cases with multiple hepatic tumors (primary 5 cases or secondary 7
cases) were selected. All patients underwent the three dimensional CT simulation
in free breathing. For each patient, RapidArc plans with single or two 358
degrees arcs using 6MV X or 15MVX-ray were designed respectively, the
prescription dose was 2Gy/Fractionx25 Fractions. The dosimetric differences were
compared among RapidArc plans. RESULTS: All of RapidArc plans can meet the
clinical requirement. There were no significant difference were found in the
conformity index (CI), homogeneity index (HI), the maximum dose and the minimum
dose of PTV among RapidArc plans(P>0.05), and all the CI can get to 0.91 and HI
can get to 0.88. In the RapidArc plans with two 358 degrees arcs, the V5,V10,V15
of normal liver were higher than with single arc, while V20, V25, V30, V35, V40
were lower than with single arc. The radiation dose of normal liver, stomach,
duodenum and spinal cord differed no significantly among different plans(P>0.05).
The monitor units of RapidArc plans using 6MV X- ray increased 12% compared to
15MV averagely. CONCLUSIONS: The 6MV X-ray would be selected chiefly in the
radiotherapy of multiple haptic tumor using RapidArc with single or two whole
arcs.
PMID- 28517464
TI - SU-E-T-472: Characterization of the Very High Energy Electrons, ISO - 250 MeV
(VHEE) Beam Generated by ALPHA-X Laser Wakefield Accelerator Beam Line for
Utilization in Monte Carlo Simulation for Biomedical Experiment Planning.
AB - PURPOSE: Progress in the development of compact high-energy pulsed laser- plasma
wakefield accelerators is opening up the potential for using Very High Energy
Electron (VHEEs) beams in the range of 150 - 250 MeV for biomedical studies.
Initial experiments using VHEE for this purpose have been carried out using the
ALPHA-X laser-plasma wakefield accelerator beam line at the University of
Strathclyde, Glasgow, UK. The purpose of this investigation is to use Monte Carlo
simulations to plan experiments and compare with characterization of the
interaction of the VHEE beam using a dosimeter. METHODS: An experiment using the
VHEE beam to irradiate a muscle-equivalent BANG polymer gel dosimeter has been
carried out. Simulations have been used to prepare for the experiments. These
were undertaken using the expected average energy for a pulse set and an energy
spread approximated by Gaussian distribution. The model was implemented in FLUKA
Monte Carlo code with follow up modeling using the Geant4 toolkit. The results
have been compared with 1mm3 voxel laser CT based measurements of the dose
deposited in the BANG dosimeter and with measurement of the induced
radioactivity. RESULTS: The results of the measured dose from induced
radioactivity have been compared with data from the FLUKA simulations. The beam
model based on an average energy of particles in irradiation gives an acceptable
estimate of the induced radioactivity and the dose deposited in the BANG
dosimeter. Comparison with the dosimeter scanned profiles shows that the
structure of the spectra of VHEE beams in the experiment and secondary scattered
particles in the beam line should be accounted for in any model. Such model
description of the VHEE beam for the ALPHA-X beam line has been developed.
CONCLUSIONS: Monte Carlo simulations using the FLUKA code is an efficient way to
plan a VHEE experiment and analyze data from measurements.
PMID- 28517466
TI - SU-E-T-483: Delay Treatment or Switch to Different Machines? Dosimetric Effect
and Tumor Control Probability.
AB - PURPOSE: If the Linac is unavailable during the IMRT treatment schedule, the
patient can be switched to a different Linac or prostpond treatment until the
origonal Linac is available. The resulting dosimetric difference is estimated and
the compromise in the TCP is estimated for both scenarios. This work investigates
the feasibility and rationale of switching patients between different
accelerators for IMRT in contrast to prostponing the treatment. METHODS: We
performed Monte Carlo simulations of photon beams from different Linac models and
vendors. Prostate and head and neck treatment plans for Siemens Primus, Primart,
Artiste and Varian-21Ex/IX accelerators are studied in this work. Dose
distributions for given plans are recalculated using different beam data with the
same nominal energy from different Linacs. We have compared DVHs, the maximum,
the minimum and the mean dose to the target and critical structures due to
switching accelerators. In the process of switching a treatment plan to a
different accelerator, there are issues, such as optimum penumbra compensation,
dose distribution at the boundary of target and critical structures and multileaf
collimator (MLC) leaf width effects, needed to be considered and verified with
measurements. In making the final decision whether to switch machines, the TCP
based on a linear-quadratic model with time factor is considered. RESULTS: Two
DVHs of two plans from Varian and Siemens models are delivered on different
machines. Slight dose coverage differences have been observed. TCP estimation
with both delayed and without delayed treatments is calculated. Undesired drop of
TCP is observed with treatment gap. CONCLUSIONS: Based on the analyses done in
this work, it is therapeutically more beneficial to switch a patient to a
different machine than to postpone a treatment until the original machine is
available, especially for fast growing tumors such as head and neck cancers.
PMID- 28517467
TI - SU-E-T-454: Dosimetric Comparison between Pencil Beam and Monte Carlo Algorithms
for SBRT Lung Treatment Using IPlan V4.1 TPS and CIRS Thorax Phantom.
AB - PURPOSE: To compare measured and calculated doses using Pencil Beam (PB) and
Monte Carlo (MC) algorithm on a CIRS thorax phantom for SBRT lung treatments.
METHODS: A 6MV photon beam generated by a Primus linac with an Optifocus MLC
(Siemens) was used. Dose calculation was done using iPlan v4.1.2 TPS (BrainLAB)
by PB and MC (dose to water and dose to medium) algorithms. The commissioning of
both algorithms was done reproducing experimental measurements in water. A CIRS
thorax phantom was used to compare doses using a Farmer type ion chamber (PTW)
and EDR2 radiographic films (KODAK). The ionization chamber, into a tissue
equivalent insert, was placed in two position of lung tissue and was irradiated
using three treatments plans. Axial dose distributions were measured for four
treatments plans using conformal and IMRT technique. Dose distribution
comparisons were done by dose profiles and gamma index (3%/3mm). RESULTS: For the
studied beam configurations, ion chamber measurements shows that PB overestimate
the dose up to 8.5%, whereas MC has a maximum variation of 1.6%. Dosimetric
analysis using dose profiles shows that PB overestimates the dose in the region
corresponding to the lung up to 16%. For axial dose distribution comparison the
percentage of pixels with gamma index bigger than one for MC and PB was, plan 1:
95.6% versus 87.4%, plan 2: 91.2% versus 77.6%, plan 3: 99.7% versus 93.1% and
for plan 4: 98.8% versus 91.7%. It was confirmed that the lower dosimetric errors
calculated applying MC algorithm appears when the spatial resolution and variance
decrease at the expense of increased computation time. CONCLUSIONS: The agreement
between measured and calculated doses, in a phantom with lung heterogeneities, is
better with MC algorithm. PB algorithm overestimates the doses in lung tissue,
which could have a clinical impact in SBRT lung treatments.
PMID- 28517468
TI - SU-E-T-494: Variation of Mucosal Dose in Head-And-Neck Radiotherapy: A Phantom
Study Using Monte Carlo Simulation.
AB - PURPOSE: This phantom study investigated variations of mucosal dose on photon
beam energy, beam angle, multi-beam configuration and mucosal thickness, when
using small photon fields in head-and-neck radiotherapy. METHODS: Cylindrical
mucosa phantoms with bone and air heterogeneities were created with mucosal
thickness (normal tissue) equal to 1, 2 and 3 mm. For dosimetric comparison,
corresponding homogeneous phantom with all heterogeneities replaced by normal
tissue was also used. These phantoms were irradiated by photon beams with field
size = 1 * 1 cm2 . Beam energies of 6 and 18 MV were used with beam angles varied
to 0 degrees , 90 degrees and 180 degrees . Moreover, multi-beam configurations
of 2, 4 and 8 beams were used, and doses along the central-beam axis in the
mucosal tissue were calculated using Monte Carlo simulations (EGSnrc code).
RESULTS: For beam angle equal to 0 degrees , the mucosal surface doses decreased
slightly with an increase of the mucosal thickness (1-3 mm), while the surface
dose of the 6 MV photon beam was decreased more significantly than the 18 MV. For
beam angle equal to 180 degrees , variation of muscosal surface dose with its
thickness was found insignificant. For different multi-beam configurations, it
was found that the variation of mucosal dose on its thickness became
insignificant when the number of photon beams around the mucosa was increased. In
addition, the change of mucosal dose due to the bone and air heterogeneities
depended on the photon beam energy, beam angle and muscosal thickness.
CONCLUSIONS: It is concluded that mucosal dose depends on variations of beam
energy, beam angle, multi-beam configuration and mucosal thickness for small
photon fields. The dosimetric information in this study should be considered in
studying the mucosal complications in head-and-neck IMRT, so that an optimized
treatment strategy to minimize mucosal complications can be developed. This study
is supported by the Deana?TMs Fund Grant in the University of Toronto.
PMID- 28517469
TI - SU-E-T-465: Exploring the Dosimetric and Tumor Control Consequences of Prostate
Seed Loss and Migration.
AB - PURPOSE: Once implanted, prostate brachytherapy seeds are vulnerable to loss and
movement. A general estimation of these effects may be useful for making patient
care decisions when seeds are lost after the post-implant scan. The goal of this
work was to explore the dosimetric and radiobiological effects of the types of
seed loss and migration common in prostate brachytherapy. METHODS: This study
evaluates five patients. For each, three treatment plans were created using
Iodine-125, Palladium-103 and Cesium-131. The three seeds closest to the urethra
were identified and modeled as seeds lost through the urethra. The three seeds
closest to the exterior of prostatic capsule were identified and modeled as those
lost from the prostate periphery. The seed locations and organ contours were
exported from Prowess and used by in-house software to perform the dosimetric and
radiobiological evaluation. The radiobiological evaluation was based on the
linear-quadratic model. Seed loss was simulated by removing 1, 2 or 3 seeds near
the urethra 0, 2 or 4 days after the implant or removing seeds near the exterior
of the prostate 14, 21 or 28 days after the implant. RESULTS: Loss of 1, 2 or 3
seeds through the urethra resulted in D90 reduction of 2%, 5% and 7% loss
respectively. Due to delayed loss of peripheral seeds, effects were less severe
than for loss through the urethra. However, while the dose reduction is modest
for multiple lost seeds, the reduction in tumor control probability was minimal.
CONCLUSIONS: The goal of this work was to explore the dosimetric and
radiobiological effects of the types of seed loss and migration commonly seen in
prostate brachytherapy. The results presented show that loss of multiple seeds
can cause a substantial reduction of D90 coverage. However, the dose reduction
was not seen to significantly reduce tumor control probability.
PMID- 28517470
TI - SU-E-T-476: GPU-Based Monte Carlo Radiotherapy Dose Calculation Using Phase-
Space Sources.
AB - PURPOSE: To design an efficient method for utilizing phase-space source models in
the GPU-based Monte Carlo (MC) dose calculation engine gDPM. METHODS: In GPU
based MC algorithms, particles are transported in parallel on different threads.
Particles of different types and energies can require significantly different
execution times. This can cause "thread divergence" and lower efficiency when
source particles are read sequentially from a phase-space file. We have developed
a strategy for utilizing phase- space files in a GPU compatible manner whereby
the particles are grouped into phase-space-lets (PSLs) by type, energy, and
location in the phase- space plane. This allows for dose calculations using only
particles inside the field opening defined by the secondary collimators. For
validation, the gDPM PSL implementation is compared with DOSXYZnrc using a
BEAMnrc phase-space source model as input. RESULTS: Two phase-spaces were
generated using a BEAMnrc head model of a 6MV Varian Clinac 21EX, one above the
upper jaws used to generate PSLs for gDPM and the other below the lower jaws used
for DOSXYZnrc dose calculation. Profiles and depth dose curves for a variety of
field sizes were generated in a water phantom. The agreement between gDPM and
DOSXYZnrc is within 2% for all field sizes. For the 10 cm * 10 cm field, the
calculation times of 650 million histories were 147 CPU hours and 54 GPU seconds
for DOSXYZnrc and gDPM, respectively. In addition, we have tested the gDPM PSL
implementation for dose calculation in a realistic 7-field IMRT tongue treatment
plan. The calculation times were 59 CPU-hours and 66 GPU- seconds for DOSXYZnrc
and gDPM for 485 million histories, respectively. Gamma pass rate for the two
dose distributions was 99.54% for 3 mm/3% criteria within the 10% isodose.
CONCLUSIONS: Methods for the efficient use of phase-space sources for GPU-based
MC dose calculations have been developed.
PMID- 28517471
TI - SU-E-T-447: Evaluation of the Anisotropic Analytical Algorithm (AAA)
Heterogeneity Correction Dose Calculation in Flattened and Flattening- Filter
Free (FFF) Beams for High Energy X-Ray Beams Using the Radiological Physics
Center (RPC) Lung Phantom.
AB - PURPOSE: Compare the accuracy of AAA heterogeneity corrected dose calculation
algorithm for high energy x-ray beams (>10 MV) for flattened and FFF beams using
RPC anthropomorphic thorax phantom. METHODS: Six static beam SBRT treatment plans
were created using the Varian Eclipse treatment planning system (TPS) AAA
v.8.9.08 heterogeneity correction algorithm. Two flattened beam plans (6 MV and
18 MV) and four other plans (6 MV, 6 MV FFF, 10 MV FFF and 15 MV) were delivered
using a Clinac 21EX and TrueBeam STx, respectively. Prescription dose/coverage, 6
Gy to 95% PTV, and constraints were the same for all plans. The phantom contained
radiochromic films in the 3 major planes and TLDs in the heart, spine, and tumor.
Point doses and 2D dose distributions were exported from the Eclipse TPS and
compared with the measured doses. The gamma index analysis evaluation criteria of
+/-5% dose to agreement and 3 mm distance to agreement was used. RESULTS: TLD to
TPS tumor point dose ratios were 0.971+/-0.006(6MV) and 0.957+/-0.002(6MV),
0.995+/-0.005(15MV), 1.114+/-0.006(18MV), and 0.957+/-0.003(6MV FFF), 0.974+/
0.011(10MV FFF) for the six plans. Using +/-5%/3mm gamma analysis criteria, the
average passing rates for all three films were 96.3% and 95.5%, 97.4%, 66.1%,
93.7%, and 96.3% for the 6 MV, 6 MV, 15 MV, 18 MV, 6 MV FFF, and 10 MV FFF plans,
respectively. Dose profiles were also evaluated. CONCLUSIONS: The current RPC
credentialing criteria are: RPC/Inst. tumor dose ratio of 0.97+/-0.05 and 85% of
the pixels in each film plane must pass a +/-5%/5mm gamma index analysis. These
data demonstrate that the AAA heterogeneity correction dose calculation algorithm
is accurate for photon energies in 6-15 MV range for flattened and FFF beams.
Heterogeneity corrected dose calculations for photon energies >15 MV were not
accurate. Work supported by grants CA10953 and CA81647 (NCI, DHHS).
PMID- 28517472
TI - SU-E-T-487: Spatial Assessment of Dose Distributions for Patients with Lung
Cancer Treated with Stereotactic Ablative Radiotherapy (SABR).
AB - PURPOSE: We hypothesize that PTV margin dose is an important factor for local
tumor control. We evaluated dose distributions for patients originally treated
with pencil-beam (PB)-based plans and retrospectively calculated with Monte Carlo
(MC) method, with emphasis on the spatial region between the ITV and PTV (PTV
margin), where the largest dose differences were expected. METHODS: Forty-six
stage I-II lung cancer patients with 51 lesions treated with SABR were
retrospectively analyzed (23 central and 28 peripheral tumors). All patients
received 4DCT imaging, and an ITV was generated from the maximum intensity
projection and subsequent review of four 4DCT phases. An isotropic 3mm ITV-to-PTV
margin was used. The iPlan TPS was used to generate the original treatment plans
using PB-based heterogeneity correction. MC doses were recalculated using the
same MUs as in the PB plan. Dose distributions for the ITV, PTV-margin, and PTV
were analyzed using generalized equivalent uniform dose (gEUD) with a = - 20.
Student's paired t-test elucidated differences between PB and MC-based gEUD and
the two different tumor locations. RESULTS: Mean ITV and PTV volumes were 24.2 cc
(range: 2.2 to 99.3 cc) and 50.4 cc (range: 6.4 to 229.7 cc), respectively. The
mean gEUDs of ITV, PTV-margin and PTV, normalized to PB-based 100% isodose were
1.02+/-0.04, 1.01+/-0.04 and 1.01+/-0.04 for PB-based plans, compared to 0.94+/
0.06, 0.88+/-0.08 and 0.90+/-0.08 (all p<0.05) for MC-based plans. The maximum
overestimations with the PB algorithm in the PTV-margin average dose were 10.4%
and 19.6% (p < 0.05) for peripheral tumor cases and central tumor cases,
respectively. CONCLUSIONS: PB-based dose distributions showed the highest dose
overestimation (relative to MC) in the PTV-margin spatial region. Analysis of
spatial dose differences is an important precursor toward assessment of patterns
of-local failure, to be investigated in future work to explore possible
association between dose and regions of failure. Acknowledgement: supported in
part by grants from NIH R01 CA106770 and from Varian Medical Systems.
PMID- 28517473
TI - SU-E-T-458: Radiobiological Comparison of Single and Dual-Isotope Prostate Seed
Implants.
AB - PURPOSE: Several isotopes are available for low dose-rate brachytherapy of the
prostate. Currently, most implants use a single isotope. However, the use of dual
isotope implants may yield an advantageous combination of characteristics such as
half-life and relative biological effectiveness. However, the use of dual-isotope
implants complicates treatment planning and quality assurance. Do the benefits of
dual-isotope implants outweigh the added difficulty? The goal of this work was to
use a linear-quadratic model to compare single and dual-isotope implants.
METHODS: Ten patients were evaluated in this study. For each patient, six
treatment plans were created with single or dual-isotope combinations of 1251,
103Pd and 131Cs. For each plan the prostate, urethra, rectum and bladder were
contoured by a physician. The biologically effective dose was used to determine
the tumor control probability and normal tissue complication probabilities for
each plan. Each plan was evaluated using favorable, intermediate and unfavorable
radiobiological parameters. The results of the radiobiological analysis were used
to compare the single and dual-isotope treatment plans. RESULTS: Iodine-125 only
implants were seen to be most affected by changes in tumor aggressiveness.
Significant differences in organ response probabilities were seen at common dose
levels. It was recognized that these differences were likely a result of
suboptimal initial seed strengths. After adjusting the initial seed strength to
maximize complication-free tumor control the differences between isotope
combinations were minimal. This result was true even for unfavorable tumors.
CONCLUSIONS: The objective of this work was to perform a radiobiologically based
comparison of single and dual-isotope prostate seed implant plans. For all
isotope combinations, the plans were improved by varying the initial seed
strength. For the minimally-optimized treatment plans, no substantial differences
in predicted treatment outcomes were seen among the different isotope
combinations.
PMID- 28517474
TI - SU-E-T-498: A Preliminary Monte Carlo Simulation Study of the Varian TrueBeam
Linear Accelerator.
AB - PURPOSE: To benchmark the quality of Monte Carlo simulation results with the
commissioning data for a Varian TrueBeam accelerator. METHODS: IAEA phase space
files of a 6MV TrueBeam accelerator provided by Varian were implemented using
GEANT4 Monte Carlo code. The present application consisted of upper and lower
jaws and a cubic water phantom of 0.125 cubic meters in volume. Both radial and
transverse dose profiles (in 5 different depths) and a central axis percentage
depth dose (PDD) curve were recorded in the phantom. Field sizes of as small as
4*4 cm2 and as large as 30*30 cm2 were simulated with 2.0E9 incident particles
each. The results were then compared with our commissioning data performed in a
Wellhoffer Blue Phantom with a 0.13cc ion-chamber and a 0.8*0.8mm diode. RESULTS:
The GEANT4 simulated PDD curve compared favorably within ~2% against the measured
ion-chamber PDD for all field sizes and against the measured diode PDD for all
fields less then 20*20cm2 . The simulated in-plane and cross-plane profiles
compared well within 2 mm at the 50% level against the measured profiles for all
field sizes. CONCLUSIONS: These results demonstrate the feasibility of utilizing
Monte-Carlo simulated beam data in the commissioning of a linear accelerator. The
increasing speed and capability of the desktop computer will Result in the
adoption of Monte- Carlo techniques for dosimetric calculations.
PMID- 28517475
TI - SU-E-T-469: The Effects of Patient Anatomy and Parallel Magnetic Fields on
Beamlet Dose Distributions.
AB - PURPOSE: Beamlets are generated in a patient geometry in the presence of a
magnetic field to investigate the effects of tissue density and magnetic field on
beamlet dose distributions, which is important for the optimization of photon
fluence to be delivered by a linac-MR system. METHODS: 50*50 mm2 fields were
placed with isocenter in the middle of a patient's right lung. Each treatment
field was decomposed into 100 beamlets (each 5*5 mm2 ). BEAMnrc scored the
particle phase space at 100.2 cm from the source in the linac-MR geometry
(isocentre at 126 cm) with parallel magnetic fields of 0, 0.56, and 3T. DOSXYZnrc
was modified to score the energy deposited by particles from this phase space as
a function of the beamlet the particle passed through. The calculation volume of
70*46*64 voxels encompassed the patient with a voxel size of 3*3*3 mm3 . Each
beamlet was normalized to the dose calculated to a 3*3*3 mm3 voxel with isocenter
at 5cm depth in a flat water tank without a magnetic field. RESULTS: Beamlet
files were calculated on Western Canada's high performance computing cluster
(Westgrid) using 100 processors, enabling simulation of 109 histories in less
than 3 hours. The resulting files, which contained 3D dose distributions for all
100 beamlets, were 81 MB per field. The Monte Carlo uncertainty was also stored.
The gyroradii for 1 MeV electron traversing field lines at 20 degrees are 2.9mm
and 0.5mm for 0.56 and 3T fields respectively. The 0.56T parallel magnetic field
has a small effect compared to the distortion of the beamlet introduced by the
presence of lung. CONCLUSIONS: The effect of tissue heterogeneities is more
significant than the effect of a 0.56T parallel magnetic field. A 3T field
refocuses the dose in lung to the beamlet path and significantly reduces the
lateral electron scatter.
PMID- 28517476
TI - SU-E-T-480: Updating the Planar Patterson-Parker Table Using the TG-43U1
Recommended Dosimetric Parameters.
AB - PURPOSE: In this project, the Patterson-Parker Table has been updated for Cs-137
and Ir-192 sources using their recent TG-43U1 dosimetric data. In addition, dose
uniformity for the different loading schemes as a function of implant area has
been verified. METHODS: The updated Paterson-Parker tables have been generated
for planar implants with Cs-137 and Ir-192 sources using their published TG-43U1
dosimetric parameters. Accuracies of the updated tables were examined by two
independent methods, namely, Monte Carlo simulation technique and using a
commercially available treatment planning system. In addition to the dose values
along the central axis of the implant, dose profiles along two orthogonal
directions have been evaluated for selection of the optimum radioactivity
distribution in each implant geometry. RESULTS: The results of these
investigations show that for the same implant size the mg.hr required for
delivery of a given dose with Cs-137 is not identical to that of Ir-192. In
addition, some differences between the updated Table and the published Paterson
Parkers Tables have been observed. Independent Monte Carlo simulations and
treatment planning data for multi-seed implant indicated the accuracy (less than
+/-5%) of the updated Table. CONCLUSIONS: This work gives complete updated
Paterson-Parker Tables for two of the commonly utilized brachytherapy sources.
For delivery of a given dose, significant differences (approximately 35%) have
been observed between the traditional Paterson-Parker Table and the updated
Tables. These differences are attributed to the differences of tissue
attenuation, 2D anisotropy functions as well as the availability of the new
source dosimetry.
PMID- 28517477
TI - SU-E-T-471: Beam Properties of an In-Room Proton Therapy Accelerator.
AB - PURPOSE: To quantify basic beam properties of the first gantry-mounted proton
therapy accelerator, situated in the treatment room and delivering beam to the
patient without any intermediate bending magnets. METHODS: Monte Carlo
simulations for prototype beamlines of the Mevion S250TM proton therapy system
were performed using MCNPX. For each configuration, open profiles in air were
determined at 3 different positions for 3 range settings (216 profiles).
Similarly, half-beam-blocked profiles were determined for the same settings (216
profiles). Additionally, beam axis fluence profiles in air were determined for 3
range settings (72 profiles). Finally, Bragg peak depth-dose curves in water were
determined for 3 range settings (72 profiles). Using these 576 profiles, several
beamline parameters were determined for each proton range and configuration,
including virtual SAD, effective source size, and effective SAD. Additionally,
Bortfeld's analytic approximation of the Bragg curve was fit to each depth-dose
curve to determine R0, sigma and epsilon. The 72 values determined for each
parameter were compared within each configuration and across all configurations.
RESULTS: Within any configuration, the change in range was too small (=2.5 cm) to
have a large effect on any of the extracted parameters. Comparing parameters
among configurations revealed smooth trends. These parameters were then fit as a
function of range. CONCLUSIONS: The simplicity of this system results in beams
with greater similarity among configurations as compared to other proton therapy
systems. Because a beam with fixed initial energy is degraded only by tissue
equivalent materials, range straggling and beam divergence are nearly constant
across all beamline configurations. Beam parameters change smoothly as functions
of proton range, with no major discontinuities between configurations. This
suggests that the entire machine may be fully and accurately characterized in a
treatment planning system by fewer measurements than would normally be required.
PMID- 28517479
TI - SU-E-T-482: A More Accurate Bare 12 5I Spectrum.
AB - PURPOSE: To compare measured energy spectra of 125 I brachytherapy seeds with
Monte Carlo calculated energy spectra when using the bare 125 I energy spectrum
recommended by TG43 and the one presented in NCRP Report 58 and to determine the
impact of these different spectra on the calculation of the dose rate constant.
METHODS: The energy spectrum, absorbed dose at 1 cm on the bisector and air kerma
strength of 10 different 125 I seeds were calculated using the EGSnrc BrachyDose
Monte Carlo code. Energy bin width was 0.2 keV. The simulations were done with
the bare 125 I energy spectrum recommended by TG43 or NCRP Report 58. Statistical
uncertainties for the energy spectra were 0.02% and 0.1% or less for the other
clinical parameters. Results are compared with published measuredvalues. RESULTS:
There is close agreement between the measured and calculated branching ratio
generated by 125 I seeds when simulated using the spectrum presented in NCRP58.
However, for all seeds a 7% lower value is observed in the 31 keV peak when using
data suggested by TG43. On the other hand, differences in the average energy, air
kerma, absorbed dose and dose rate constant are undetectable (less than
statistical uncertainty, <0.1%) when performed with either spectrum. CONCLUSIONS:
For dosimetric parameter calculations, the bare 125 I energy spectra presented in
TG43 and NCRP58 produce indistinguishable results. However, for branching ratio
investigation purposes, there is a clear difference in the 31 keV peak between
values obtained using the different 125 I bare energy spectra. Measured 125 I
branching ratios are in close agreement with those calculated using the bare 125
I energy spectrum presented in NCRP58. Reassessment of the bare 125 I energy
spectrum recommended in TG43 is suggested.
PMID- 28517478
TI - SU-E-T-442: Assessing Vertex Beam with its Dosimetric Relevance for Intracranial
Tumours: A Computational Exploration.
AB - PURPOSE: To assess the selection of the minimal vertex beam angle for the
avoidance of organs at risk (OARs) in radiotherapy planning of brain tumors.
METHODS: Seventy patients with intracranial tumors were studied. Three field
conformal plans with co-planar or non co-planar beam arrangements with an
anterior vertex beam were used. Two methods were studied for determining the
vertex angle for avoidance of eye as organ at risk. In the standard technique,
the beam's eye view (BEV) was used to determine need of vertex beam. For the
vertex beam, the angle was approximated to avoid eyes. In the second method, the
angle from the baseplate to the posterior surface of the head and the angle from
the posterior surface of the head to the inferior-most extent of the head were
measured from sagital view. The minimum vertex angle required was calculated as
the complement of the sum of these angles. The dose volume histogram parameters
were maintained. RESULTS: Depending on the spatial location of the planning
target volume with reference to the eyes, patients were classified into 4 types:
no overlap; overlap with eye anteriorly; overlap with eye posteriorly, overlap
with eye anteriorly and posteriorly. No additional angulation, positive vertex
and negative vertex angles were needed for type 1, 2 and 3 respectively. The
angle subtended by the isocenter to the neck rest apex was the required vertex
angle for type 4. Of the 36 type 2, 3 and 4 patients the planned vertex angle was
more than the calculated vertex angle by over 5 degrees in 10 patients, and less
by over 5 degrees in 4 patients. CONCLUSIONS: A simple method for deriving the
minimal vertex beam angle for OAR avoidance in radiotherapy planning of
intracranial tumors was described and validated.
PMID- 28517480
TI - SU-E-T-453: Optimization of Dose Gradient for Gamma Knife Radiosurgery.
AB - PURPOSE: The goals of stereotactic radiosurgery (SRS) are the ablation of target
tissue and sparing of critical normal tissue. We develop tools to aid in the
selection of collimation and prescription (Rx) isodose line to optimize the dose
gradient for single isocenter intracranial stereotactic radiosurgery (SRS) with
GammaKnife 4C utilizing the updated physics data in GammaPlan v10.1. METHODS:
Single isocenter intracranial SRS plans were created to treat the center of a
solid water anthropomorphism head phantom for each GammaKnife collimator (4 mm, 8
mm, 14 mm, and 18 mm). The dose gradient, defined as the difference of effective
radii of spheres equal to half and full Rx volumes, and Rx treatment volume was
analyzed for isodoses from 99% to 20% of Rx. RESULTS: The dosimetric data on Rx
volume and dose gradient vs. Rx isodose for each collimator was compiled into an
easy to read nomogram as well as plotted graphically. The 4, 8, 14, and 18 mm
collimators have the sharpest dose gradient at the 64%, 70%, 76%, and 77% Rx
isodose lines, respectively. This corresponds to treating 4.77 mm, 8.86 mm, 14.78
mm, and 18.77 mm diameter targets with dose gradients radii of 1.06 mm, 1.63 mm,
2.54 mm, and 3.17 mm, respectively. CONCLUSION: We analyzed the dosimetric data
for the most recent version of GammaPlan treatment planning software to develop
tools that when applied clinically will aid in the selection of a collimator and
Rx isodose line for optimal dose gradient and target coverage for single
isocenter intracranial SRS with GammaKnife 4C.
PMID- 28517481
TI - SU-E-T-493: Accelerated Monte Carlo Methods for Photon Dosimetry Using a Dual-GPU
System and CUDA.
AB - PURPOSE: To develop a Graphics Processing Unit (GPU) based Monte Carlo (MC) code
that accelerates dose calculations on a dual-GPU system. METHODS: We simulated a
clinical case of prostate cancer treatment. A voxelized abdomen phantom derived
from 120 CT slices was used containing 218*126*60 voxels, and a GE LightSpeed 16
MDCT scanner was modeled. A CPU version of the MC code was first developed in C++
and tested on Intel Xeon X5660 2.8GHz CPU, then it was translated into GPU
version using CUDA C 4.1 and run on a dual Tesla m2 090 GPU system. The code was
featured with automatic assignment of simulation task to multiple GPUs, as well
as accurate calculation of energy- and material- dependent cross-sections.
RESULTS: Double-precision floating point format was used for accuracy. Doses to
the rectum, prostate, bladder and femoral heads were calculated. When running on
a single GPU, the MC GPU code was found to be *19 times faster than the CPU code
and *42 times faster than MCNPX. These speedup factors were doubled on the dual
GPU system. The dose Result was benchmarked against MCNPX and a maximum
difference of 1% was observed when the relative error is kept below 0.1%.
CONCLUSIONS: A GPU-based MC code was developed for dose calculations using
detailed patient and CT scanner models. Efficiency and accuracy were both
guaranteed in this code. Scalability of the code was confirmed on the dual-GPU
system.
PMID- 28517482
TI - SU-E-T-464: Impact of the Treatment Margin on Tumor Control and Normal Tissue
Complication for Prostate Treatment.
AB - PURPOSE: To investigate the consequence of treatment margin reduction on normal
tissue complication probability (NTCP) and tumor control probability (TCP) of
prostate external beam treatment. METHODS: Intensity modulated rotational
radiotherapy plans were generated for 10 prostate patients with 6 different
posterior margin sizes from 5mm to 0. The prescription dose is 80Gy for 40
treatment fractions. The dose distributions were recalculated with consideration
of the intrafractional motion and the localization error. The statistical
uncertainties of the intrafractional motion and the localization error were
derived based on the motion tracking data recorded by the Calypso 4D localization
system for a large patient population. The TCP and NTCP were calculated based on
the dose volume histograms (DVH) of prostate and rectum for plans with different
margins using an equivalent uniform dose (EUD) based biological model. The 50%
tumor control dose (TCD50) of 60Gy for prostate and the median toxic dose (TD50)
of 55Gy for rectum were used in the calculation. RESULTS: The minimum dose of the
prostate and the mean dose of the rectum dropped with the decrease of the
treatment margin. When the posterior treatment margin was reduced from 5mm to
zero, the EUD of prostate decreased from 83Gy (+/-0.5Gy) to 81Gy (+/-0.5Gy) and
the TCP dropped from 93.2% (+/-0.1%) to 91.7% (+/-0.1%), the EUD of the rectum
decreased more significantly from 48.9Gy (+/-0.4Gy) to 32.5Gy (+/-0.5Gy) and the
NTCP dropped from 13.3% (+/-1.5%) to 0.03% (+/- 0.01%). CONCLUSIONS: The
treatment margin size affects the dose to the target and the nearby critical
structure. More significant impact on NTCP has been observed than on TCP. This
gives us some room to consider the quality of the patient's after-treatment life.
A wise choice of treatment margin can be made based on physician's opinion and
patient's preference on the tumor control and the quality of life.
PMID- 28517483
TI - SU-E-T-475: Nano-Dosimetric Track Structure Scoring including Biological Modeling
with TOPAS-NBio.
AB - PURPOSE: To develop a nano-dosimetric Monte Carlo simulation package, TOPAS-nBio,
based on the TOPAS (TOol for PArticle Simulations) framework that is being
developed in a collaboration between the Massachusetts General Hospital (MGH),
the SLAC National Accelerator Laboratory and the University of California, San
Francisco. The goal is to incorporate biological processes on a sub-cell level
that will provide the basis for a wide range of research in the field of
radiobiology, such as bystander effects, biological dose calculations and effects
of nano-particles on radiation therapy. METHODS: The TOPAS framework has been
utilized to extend the functionality of this tool for particle transport to
include nano- dosimetry. The physics lists of TOPAS have been extended to include
efforts by the Geant4-DNA group to model physics on nanometer scales, including
chemical processes of the first millisecond after irradiation. TOPAS-nBio uses
the functionality of TOPAS to score energy depositions on nanometer scales. A
simulation of the setup of a cell culture irradiation experiment has been used as
to test the feasibility of the project. RESULTS: Track structures for an
irradiation of a cell culture experiment were successfully obtained. Delta
electron distributions have been produced and single track delta electrons and
their energy depositions were observed. CONCLUSIONS: This study is a first step
in the development of TOPAS-nBio, a tool that aims at bringing nanometer scale
radiation physics and biology together and make Monte Carlo simulations
accessible for all radiobiology researchers. The results presented here show a
first proof of concept for the development of TOPAS-nBio.
PMID- 28517484
TI - SU-E-T-446: Effect of Dose Calculation Grid Size Variability on the Specification
of Spinal Cord Dose Tolerance for Spinal Stereotactic Body Radiation Therapy.
AB - PURPOSE: To investigate the effect of the dose grid resolution variability on the
spinal cord dose for spinal SBRT treatments. METHOD: 10 CyberKnife plans were
selected for the proximity of the PTV to the spinal cord. All dose distributions
were calculated with Monte Carlo using high spatial resolution and minimal
relative uncertainty. The plans were renormalized to a 16 Gy prescription dose
and to ensure a target coverage > 95% in order to compare the calculated dose
distributions. Each dose matrix was resampled 12 times, covering a grid
resolution range of 0.95 mm to 13.52 mm. The spinal cord DVHs were generated for
each resampled dose grid. The variations of the maximum point dose (DmaxCord) and
dose-coverage to partial volumes (D[V]) up to 5 cc were investigated against the
grid resolution. RESULTS: The mean variation of DmaxCord with grid resolution is
characterized by an inverse power law, with a sharp initial decrease leading to
potentially large underestimates of DmaxCord (24%, 40% and 55% at resolutions of
2 mm, 4 mm and 8 mm). The variability of mean D[V] values decreases from smaller
to larger grid resolutions, however large disparities are observed between
patient plans. We introduced the variability threshold volume (Vth) as a
constraint to express the dose coverage independently from the grid resolution.
For resolutions up to 8 mm, the mean Vth value is (0.96+/-0.10) cc with a
corresponding dose coverage of (26+/- 12) % relative to the initial DmaxCord
value. CONCLUSIONS: Dose distributions calculated with grid resolutions larger
than 2 mm could Result in significant underestimates of DmaxCord. Furthermore,
the sensitivity of the dose coverage to grid resolution variability is patient
dependent. Consequently, a specified cord dose tolerance should be quoted at a
particular grid resolution uniformly adopted between institutions; 2 mm or less
is an appropriate value.
PMID- 28517485
TI - SU-E-T-486: Volume and Location Dependence on the Difference Between Monte Carlo
and Pencil Beam Dose Calculations for Lung Stereotactic Body Radiation Therapy.
AB - PURPOSE: Stereotactic body radiotherapy has been an efficacious treatment
modality for early stage non-small cell lung cancer. The accuracy of dose
calculations is in question due to the presence of inhomogeneity. It was required
in several clinical trials to calculate dose without heterogeneity correction.
However, to better correlate the outcomes with the planned dose, accurate dose
calculation with heterogeneity correction is highly desirable. METHODS: We
compared the recalculated dose with Monte Carlo (MC) algorithm to the original
Pencil Beam (PB) calculations for clinical lung SBRT plans. Thirty-one clinical
plans that followed protocol guidelines were retrospectively investigated.
Dosimetric parameters D1, D95 and D99 for the PTV and D1 for organs at risk were
compared. Correlations of mean lung dose and V20 of lungs between two
calculations were investigated. RESULTS: Compared to the PB calculations without
heterogeneity correction in clinical plans, we found that in terms of D95 of PTV,
(1) the two calculations resulted in similar D95 for edge tumors with volumes
greater than 25.1cc; (2) an average overestimation of 5% in PB calculations for
edge tumors with volumes less than 25.1cc; and (3) an average overestimation of
9% or underestimation of 3% in PB calculations for island tumors with volumes
smaller or greater than 22.6 cc, respectively. With heterogeneity correction, the
PB calculation resulted in an average reduction of 23.8% and 15.3% in D95 for
island and edge lesions respectively compared to the MC calculation. For organs
at risks, no clinical meaningful differences were found among all the
comparisons. Excellent correlations for mean dose and V20 of lungs were observed
between the two calculations. CONCLUSIONS: Using a single scaling factor to
account for the differences in using heterogeneity correction may not be
sufficient. To understand dose-response relation in Lung SBRT, accurate dose
calculation such as the Monte Carlo algorithms is highly recommended.
PMID- 28517486
TI - SU-E-T-457: Multi-Mode Model - A Consistent Approach for Conventionally
Fractionated Radiotherapy and Stereotactic Body Radiotherapy.
AB - PURPOSE: The accuracy of dosimetric analysis and outcome comparison between
conventionally fractionated radiation therapy(CFRT) and stereotactic body
radiotherapy(SBRT) requires reliable radiobiological modeling. The aim of this
work was to further improve the multi-mode model(MMM) for both CFRT and SBRT.
METHODS: MMM assumes the existence of different modes of cell killing as a Result
of radiation damage to different parts of a cell, e.g., a single severe damage to
the DNA or two or more small damages to the membrane or DNA. The cell survival
probability can then be calculated by s=Product_(i=1,n){1-(1-e(-d/Di))(i)}, where
i represents the i-th mode of cell killing that requires i potentially
unrepairable damages to the cell as a result of radiation dose d and Di is the
dose that gives 63% probability to cause an unrepairable damage for the i-th
mode. The dose rate effect is included in MMM assuming 1/D_i=(k_i- r_i/U), where
k_i is the radiation damage rate, r_i the repair rate and U the dose rate. The
low-dose hypersensitivity is also included in the new model. RESULTS: A
comparison of the goodness-of-fit of the LQ, multitarget, USC and MMM to the
survival curve of the H460 non-small-cell lung cancer cell line showed the same
agreement between USC and MMM with the survival data, which was significantly
better than the fits to the LQ and multitarget models. The parameters used for
the LQ, multitarget and USC models were alpha=0.33Gy, alpha/beta=10Gy, D_T
=6.2Gy, D_0 =1.25Gy and D_q =1.8Gy. The parameters for MMM(n=4) were D_1=4.0Gy,
D_2=4.01Gy, D_3=3.08Gy and D_4=41Gy. CONCLUSIONS: MMM offers a superior
description of the mammalian cell survival curve in both conventional and
ablative dose ranges, which can be used for designing new fractionation schemes
and predicting and understanding treatment outcomes for both CFRT and SBRT.
PMID- 28517487
TI - SU-E-T-497: Study of Restricted Mass Stopping Power Ratio in Small Electron Tube
Fields.
AB - PURPOSE: Electron tubes with small radii are useful to treat narrow regions which
cannot accommodate normal electron applicators. In small electron fields, it is
not trivial to estimate restricted mass stopping power ratio (MSR), which is
needed to evaluate dose from ion chamber measurement. We studied MSRs in small
electron tube fields using the Monte Carlo simulation. METHODS: Electron tubes
with radii, 3 and 2.5 cm, were used in this study. Nominal electron energies were
6 and 9 MeV. There were two types of tubes. One has a normal cut but the other
has a 45-degree cut. For the normal cut tube, percent depth dose (PDD) in water
was evaluated along the center of axis (CAX) of a beam. For the 45-degree cut
tube, PDD was evaluated along the vertical line from the intersection of the CAX
and the phantom surface with 45-degree gantry angle. The MSRs and mean electron
energies were calculated using the Monte Carlo simulation. RESULTS: We found good
agreement between the measured and calculated PDDs. The changes of mean energies
from those in the 10*10 cm2 field at the depth of maximum dose (dmax) were very
small for the normal cut electron tubes. For the 45-degree cut tubes, the changes
of mean energies at dmax were less than 1 MeV. The MSRs in the normal cut tube
fields were almost the same as those in the 10*10 cm2 field at the corresponding
depths. The MSRs for the 45-degree cut tubes deviated from those in the 10*10 cm2
by about 1% (1.5 % at most). CONCLUSIONS: We evaluated the mean energies and MSRs
in small electron tube fields. The deviations of them from the values in the
10*10 cm2 were small. The maximum difference of MSR was 1.5% in 45-degree cut
tube fields. This work was supported by KAKENHI (23791449), Japan Society for the
Promotion of Science, and Cancer Professional Training Plan, The Ministry of
Education, Culture, Sports, Science and Technology, Japan.
PMID- 28517488
TI - SU-E-T-468: Gamma Knife Perfexion Dosimetry: A Monte Carlo Model of One Sector.
AB - PURPOSE: We have implemented a Monte Carlo (MC) based dose computation model of
one sector of the Gamma Knife Perfexion (GK PFX) using the Penelope MC dosimetry
codes. The single sector simulation was rotated about the z-axis to model all
eight GK sectors. GK dosimetric aspects examined include: 1) output factors (OF)
for each of the three GK collimator sizes (4, 8, 16 mm), 2) OFs for each source
row and collimator size, and 3) dose distribution profiles along the x- and z
axes, compared to film measurements and dose calculations from the Leksell
GammaPlan (LGP) workstation. METHODS: We defined the internal GK PFX geometry in
Penelope with the aid of vendor-supplied proprietary information. A single source
per row was modeled for five rows for each of the 3 collimators (15 beams
modeled). MC simulations were carried out on a Linux cluster. Phase space files
(PSFs) were collected for the 15 modeled collimators then rotated about the z
axis to model the sector of 24 sources per collimator. 3D dose distributions from
the MC model, film, and LGP DICOM-RT dose exports were analyzed using Matlab. For
OF calculations, a 16 cm diameter dosimetry sphere was modeled with a virtual
detector volume at its center. RESULTS: Good agreement is found for row- and
total-output factors (greatest deviation of any type < 4%) compared to reference
values. Off-axis factors closely follow LGP predicted dose distributions along
the x-axis and differ on the inferior side of the z-axis. CONCLUSIONS: Detailed
geometric representations (radiation source, device components) of the GK PFX are
required for high fidelity MC simulations. Calculated GK PFX OF values depend on
the simulated detector volume size (4 mm OF most dependent). Our model shows
strong agreement for the GK PFX OFs and dose profile curves compared to reference
values. Non-disclosure agreement for proprietary information with Elekta AB. No
financial contribution.
PMID- 28517489
TI - SU-E-T-479: Skin Dose from Flattening Filter Free Beams: A Monte Carlo
Investigation.
AB - PURPOSE: Flattening filter free (FFF) beams in radiotherapy have advantages such
as shorter treatment delivery time and lower out-of-field dose compared with
conventional flattened beams. This study investigates in detail the skin dose
induced by FFF beams from a TrueBeam accelerator (Varian Medical Systems, Palo
Alto, CA) using Monte Carlo method. METHODS: Phase space files generated using
real geometry of a TrueBeam accelerator above the jaws, were used as the input
radiation source files in beam simulation for various field sizes using BEAMnrc.
Phase space files for various field sizes were generated at the phantom surface.
DOSXYZnrc was used for dose calculations in phantom and in patient using the
generated phase space files as source input files. RESULTS: The calculated
percentage depth dose curves and profiles in water agreed with measurements
within +/- 2% for the high dose region and +/-2 mm in the penumbra. The peak
fluence of a 6 MV FFF beam with the same electron beam incident on the target is
about 3 times that of a flattened beam . The mean energy of a 6 MV FFF beam is
0.92-0.95 MeV while it is 1.18-1.30 MeV for the flattened beam. Due to the mean
energy difference, the dose in a 6 MV FFF beam is about 6% (of the maximum dose,
or 12% of local dose) higher at depth of 1 mm compared with a flattened beam.
CONCLUSIONS: Due to the lower mean photon energy, in an FFF beam the surface
(skin) dose is slightly higher compared to the conventional flattened beam of the
same field size.
PMID- 28517490
TI - SU-E-T-450: An Evaluation Study of Dose Calculation Algorithms for Stereotactic
Body Radiation Therapy in Heterogeneous Phantom.
AB - PURPOSE: In Stereotactic body radiation therapy (SBRT) higher dose per fraction
is delivered to patients and thus the need for an accurate dose computation is
further elevated. However under such conditions of small field geometries, the
electronic equilibrium can be lost, making it challenging for the dose
calculation algorithm to accurately predict the dose, especially in the presence
of tissue heterogeneities. Thus the aim of this study is to evaluate the
performance of the algorithms implemented in our treatment planning system.
METHODS: In this study different phantoms were designed to model the lung with a
small tumor volume of sizes that are usually encountered in SBRT. Solid water and
cork slabs were used in constructing the phantom body. Perspex pieces of
different diameters were created to be inserted in precut holes in the cork to
simulate the tumor. The various dose calculation algorithms that are implemented
in our CMS XIO planning system were then used for dose calculation inside the
target. RESULTS: A significant discrepancies between maximum, minimum and mean
dose for PTV was found between Clarkson, FFT Convolution, Fast superposition and
superposition algorithms in dose calculation for the lung tumor. The FFT
Convolution and Clarkson algorithms have higher calculated minimum dose than that
predicted by the superposition and the fast superposition algorithm. A percentage
difference as high as 62.5% was obtained between Clarkson and the superposition
algorithm in the estimated minimum dose. A percentage difference up to 13.4% was
obtained between the FFT Convolution and the superposition algorithm for the
estimated maximum dose. Superposition and fast superposition showed little
discrepancies for maximum, minimum and mean dose for the PTV. CONCLUSION: It is
very critical to address the accuracy of dose computation for SBRT as a
significant dose overestimation can occur inside the target due to the
heterogeneous geometries.
PMID- 28517491
TI - SU-E-T-490: Comparison of XVMC Monte Carlo Dose Calculations with Eclipse AAA
Calculations for RapidArc Plans.
AB - PURPOSE: The consistency between the AAA and XVMC algorithm in the treatment
planning for RapidArc is investigated. While the majority of the radiation field
is blocked by the MLC system, multiple small dose islands with MLC opened only
slightly can be observed in one control point. This raises questions on how
accurate the clinically used AAA algorithm in Eclipse is able to calculate
RapidArc dose distributions. The fast Monte Carlo Code XVMC was used as a
benchmark to test the AAA algorithm. METHODS: RadpidArc plans of 25 patients were
calculated with AAA and XVMC. The patient cohort consisted of 4 different cancer
sites (H&N, upper abdominal, lung, prostate). Dose distributions, PTV and OAR
coverage were compared looking at the PTV mean dose Dmean, the volume V95% of the
PTV receiving 95% of the prescribed dose, the dose D95% delivered to 95% of the
PTV Volume, the percentage PTV mean dose with respect to the prescribed dose
Dmean/prescr and OAR mean dose. RESULTS: The recalculation of RapidArc plans
yielded good agreement of both calculation algorithms for treatment plans of all
four cancer sites. PTV mean dose differences of AAA and XVMC were found to be in
between -0.11% and 4.89% of the prescribed dose. The mean dose difference found
was 0.48+/-0.77 Gy. Local dose differences were found when comparing dose
distributions in regions of big mass density differences and in high dose
regions. One head and neck plan and one prostate plan revealed significant
differences in PTV coverage (DeltaDmean=3.25 Gy) and OAR mean dose (prostate mean
dose -13.71 Gy) respectively. CONCLUSIONS: The vast majority of treatment plans
calculated with the AAA algorithm were found to agree within the expected and
acceptable tolerances compared to XVMC results. Nevertheless in some cases dose
differences were observed that could be of clinical significance. This work was
funded by a Varian grant. Wolfram Laub is working in the physics group of CMS.
PMID- 28517493
TI - Accuracy of computed tomography for detecting hepatic steatosis in donors for
liver transplantation: A meta-analysis.
AB - BACKGROUND: The accuracy of computed tomography (CT) for detecting donor hepatic
steatosis (HS) before liver transplantation is not well established. METHODS: A
meta-analysis was performed to determine the accuracy of CT for HS detection in
liver donor candidates. Pooled sensitivity, specificity, positive and negative
likelihood ratios, hierarchical summary receiver operating characteristic (HSROC)
curves, and the area under the curve (AUC) were estimated using HSROC and
bivariate random-effects models. RESULTS: Twelve studies involving 1782 subjects
were eligible for this meta-analysis. For detecting significant HS (>10%-30%
steatosis in liver pathology) with CT in liver donors, the pooled sensitivity,
specificity, positive likelihood ratio, and negative likelihood ratio were 0.81
(95% confidence interval [CI]: 0.70-0.89), 0.94 (95% CI: 0.90-0.96), 13.7 (95%
CI: 8.1-23.1), and 0.20 (95% CI: 0.12-0.33). The AUC was 0.95 (95% CI: 0.92
0.96). For detecting the presence of HS, these corresponding diagnostic estimates
were 0.50 (95% CI: 0.36-0.64), 0.90 (95% CI: 0.83-0.95), 5.2 (95% CI: 3.1-8.9),
0.55 (95% CI: 0.42-0.72), and 0.80 (95% CI: 0.76-0.83). Moderate-to-high
heterogeneity was detected. CONCLUSION: Computed tomography shows high accuracy
in detecting significant HS while poor accuracy in detecting the presence of HS
in liver donors. Donors estimated to have significant HS by CT may avoid
unnecessary liver biopsy.
PMID- 28517494
TI - SU-F-BRCD-02: Activity Assay of a Y-90 Microsphere Sample Using a Coincidence
Detection System.
AB - PURPOSE: This work takes advantage of a newly-determined, low-uncertainty
branching ratio of the internal pair production component of Y-90 decay to
spectroscopically assay the activity of a Y-90 microsphere sample with a
coincidence detection system (CDS). METHODS: The CDS pairs a HPGe detector with a
large NaI detector. The system is able to electronically filter the
bremsstrahlung continuum from the photon spectrum by gating the energy signal
from the HPGe with the coincidence signal. This reduces the uncertainty in the
spectra measurement compared to measurements with a single HPGe detector. A
series of pulsers were used to correct for counting losses. A geometric
characterization was completed to find the optimal source position for
measurements. An efficiency calibration of the CDS was completed using a Na-22
standard source. To validate the measurement accuracy of the CDS, the activity of
a Y-90 standard activity solution from the NIST SRM program was determined and
compared to the value given by NIST. The CDS was then used to determine the
activity of a Y-90 microsphere sample. This value was compared to the 3.0 GBq
value given by the manufacturer. RESULTS: The activity determined with the CDS
was within 2.6% from the given activity of the NIST SRM source, which is within
the expanded uncertainty associated with the CDS measurement. The activity of the
Y-90 microsphere sample was determined to be 3.72 GBq +/- 1.9%. This is 19%
higher than the manufacturer-stated activity of 3 GBq. This is outside the
manufacturer-stated uncertainty of +/-10%. CONCLUSIONS: The ability of CDS to
determine the activity of a Y-90 source has been validated with comparison to a
NIST Y-90 standard activity solution. The use of the CDS has been extended to
determine the activity of a Y-90 microsphere sample.
PMID- 28517495
TI - SU-E-T-621: Comprehensive Study of Head and Neck IMRT Parameters on Planning and
Delivery Efficiency, Plan Quality, and Dose Accuracy.
AB - PURPOSE: To optimize planning and delivery efficiency, and quality of head and
neck IMRT through the evaluation of planning parameters. This study also serves
to identify the impact on dose accuracy due to calculation grid size. METHODS:
Eleven head and neck patients, 45 trials per patient (495 trials in total), were
evaluated varying IMRT parameters of dose grid, minimum MU per segment, minimum
segment area, and control point number. Plans were recomputed on Pinnacle
Treatment Planning System (TPS), and scaled to the planning target volume (PTV)
constraint of 95% volume. Differential dose volume histograms (DVHs) were
exported, and a program was written to compile DVH results. Plans were delivered
on an Elekta Synergy linear accelerator to assess delivery time. Plan quality,
calculation time, and delivery time served as this study's endpoints. RESULTS:
The 4 mm dose grid with 2 mm fluence grid in each direction, saving 1/3 the
computation time, were most comparable by DVH results to the 2 mm dose and
fluence grid. Dose uncertainty due to dose calculation grid effect was as high as
8.2%, 5.5 Gy for PTVs and 13.3%, 2.1 Gy for organs at risk. Smaller volumes and
high gradient regions were more susceptible to uncertainties. Threshold values
that maintained adequate plan quality were 5 cm2 for minimum segment area and 5
MU for minimum MU. Minimum MU was more costly in terms of plan quality compared
to the minimum segment area. CONCLUSIONS: DVH differences can be effectively used
to quantify the dose grid calculation uncertainty. For minimum MU and segment
area, the DVH differences are an effect of the intensity map, defined by MLC
shape and the number of control points. Exceeding the adequate number of control
points diminishes returns of plan quality and increases patient treatment time.
PMID- 28517492
TI - Practical considerations of linear accelerator-based frameless extracranial
radiosurgery for treatment of occipital neuralgia for nonsurgical candidates.
AB - Occipital neuralgia generally responds to medical or invasive procedures.
Repeated invasive procedures generate increasing complications and are often
contraindicated. Stereotactic radiosurgery (SRS) has not been reported as a
treatment option largely due to the extracranial nature of the target as opposed
to the similar, more established trigeminal neuralgia. A dedicated phantom study
was conducted to determine the optimum imaging studies, fusion matrices, and
treatment planning parameters to target the C2 dorsal root ganglion which forms
the occipital nerve. The conditions created from the phantom were applied to a
patient with medically and surgically refractory occipital neuralgia. A dose of
80 Gy in one fraction was prescribed to the C2 occipital dorsal root ganglion.
The phantom study resulted in a treatment achieved with an average translational
magnitude of correction of 1.35 mm with an acceptable tolerance of 0.5 mm and an
average rotational magnitude of correction of 0.4 degrees with an acceptable
tolerance of 1.0 degrees . For the patient, the spinal cord was 12.0 mm at its
closest distance to the isocenter and received a maximum dose of 3.36 Gy, a dose
to 0.35 cc of 1.84 Gy, and a dose to 1.2 cc of 0.79 Gy. The brain maximum dose
was 2.20 Gy. Treatment time was 59 min for 18, 323 MUs. Imaging was performed
prior to each arc delivery resulting in 21 imaging sessions. The average
deviation magnitude requiring a positional or rotational correction was 0.96 +/-
0.25 mm, 0.8 +/- 0.41 degrees , whereas the average deviation magnitude deemed
within tolerance was 0.41 +/- 0.12 mm, 0.57 +/- 0.28 degrees . Dedicated quality
assurance of the treatment planning and delivery is necessary for safe and
accurate SRS to the cervical spine dorsal root ganglion. With additional
prospective study, linear accelerator-based frameless radiosurgery can provide an
accurate, noninvasive alternative for treating occipital neuralgia where an
invasive procedure is contraindicated.
PMID- 28517496
TI - MO-A-217BCD-02: Yttrium-90 Microsphere Therapy Planning and Dose Calculations.
AB - : Yttrium-90 microsphere therapy, a form of radiation therapy, is an increasingly
popular option for care of patients with liver metastases or unresectable
hepatocellular carcinoma. The therapy directly delivers Yttrium-90 microspheres
via the hepatic artery to specifically targeted disease sites. Following Yttrium
90 microsphere therapy, a vast majority of Yttrium-90 microspheres preferentially
lodge in neoplastic tissue due to their embolic size (mean diameter 32 μm)
and targeted trans-arterial delivery. Once embolized the microspheres do not
migrate but deposits up to 90% of its energy in the first 5 mm of tissue. Prior
to Yttrium-90 microsphere therapy, a 99mTc-MAA examination is conducted to
evaluate catheter placement and lung-shunt fraction. The lung shunt fraction and
absorbed dose estimates for lung and liver that guide Yttrium-90 administered
activity are based on nuclear medicine imaging. A review of the pre- and post
therapy imaging procedures underlying Yttrium-90 microsphere therapy will be
presented. Calculation of the lung shunt fraction and dosimetry models to
estimate radiation absorbed doses will be discussed. Radiation safety issues will
be also be reviewed. LEARNING OBJECTIVES: 1. To understand the imaging sequence
for Yttrium-90 microsphere therapy planning and dose calculations 2. To
understand calculation of lung shunt fraction and estimation of absorbed dose for
lung and liver 3. To become familiar with radiation safety and regulations
surrounding Yttrium-90 microsphere therapy.
PMID- 28517497
TI - SU-E-T-633: To Evaluate Dosemetric Differences of IMRT Lung Plans Generated from
RayStation Multi-Criteria Optimization (MCO) and Pinnacle Direct Machine
Parameters Optimization (DMPO).
AB - PURPOSE: To evaluate dosimetric differences of IMRT lung plans generated from
RayStation* Multi-Criteria Optimization (MCO) and Pinnacle Direct Machine
Parameters Optimization (DMPO) Methods: Five patients previously treated with
plans from Pinnacle v9.0 using DMPO algorithm were re-planned on RayStation
v2.4.8.180 using MCO Pareto plans with same dose constraints, beam angles and
objectives. The prescription was 60 Gy to 95% of PTV. Planning outcomes such as
D95 (95% of volume receiving the prescribed dose), D2, D1 for PTV, D33 and mean
dose for heart, V20 (volume receives at least 20 Gy) and mean dose for lung, max
dose for cord were reported for evaluation according to our clinical protocols.
The conformity of the prescription isodose volume to PTV was evaluated as
conformity index (CI). Planning time was also observed. RESULTS: The mean volume
of PTV was 356 +/- 141 cm3 . The D95 of PTV with RayStation was improved and more
uniform compared to plans from Pinnacle (59.4 +/- 0.2 vs. 59.2 +/- 0.8 Gy),
respectively. D2 and D1 of PTV were lower with RayStation plans. Mean dose and
V20 of total lung were lower for all RayStation plans with max dose of cord, and
D33 and mean dose of heart following the same trend. CI was better with
RayStation compared to Pinnacle (1.09 +/- 0.06 vs. 1.16 +/- 0.11). Planning time
was faster with RayStation from Pinnacle (few minutes. vs. minimum of 20 minutes,
approximately). CONCLUSIONS: MCO planning automatically generates a set of Pareto
optimized solutions for given objectives to allow tradeoffs between targets and
critical organs. RayStation can achieve better uniform tumor coverage with fewer
hot spots while sparing more critical structures. MCO Pareto based IMRT plans is
helpful in determining the best optimized dosimetry with shorter planning time.
PMID- 28517498
TI - MO-A-213AB-10: Scattering System Optimization for Proton Therapy.
AB - PURPOSE: To describe a method for optimization and production of a dual
scattering system for proton beam delivery. METHODS: Dual-foil passive scattering
is currently the prevalent modality for proton therapy delivery. Large uniform
proton fields are created using a 2-stage scattering system comprising an
upstream uniform lead foil (stage 1) followed by a contoured lead/Lexan foil to
provide beam and range uniformity (stage 2). Optimizing the parameters of these
foils, including thickness, contour and placement, provides not only a flat and
symmetrical radiation field with a uniform range, but also affects the overall
efficiency of the beam line. An analytical method for optimizing the scattering
system design was applied and validated with GEANT4 simulations. This method has
been used to create passively scattered therapeutic and research proton fields at
our proton therapy facility. A novel Cerrobend casting method is described that
allows for cost-effective and accurate production of this important beam-line
component. RESULTS: A number of dual scattering foil combinations for research
and therapeutic purposes have been created and were evaluated with GEANT4
simulations. We demonstrated that the use of this system can generate passively
scattered proton fields up to 60cm diameter with improved efficiency and beam
flatness over existing dual-scattering systems. Scattering system performance was
verified using physical measurements including Gafchromic film and ion chamber
data. CONCLUSIONS: This analytical method allows the user to optimize the proton
dual scattering system with respect to specific input parameters, while the
casting method provides a cost-effective way to create a unique scattering system
for a given application.
PMID- 28517499
TI - SU-E-T-644: Incorporating High Dose Inhomogeneity into SBRT Treatment Planning.
AB - PURPOSE: By encouraging greater dose inhomogeneity in the PTV, SBRT allows higher
doses to be delivered to the target, and thus improves local control and
treatment outcome. This work aims to incorporate the high dose inhomogeneity
constraint into SBRT treatment planning in safer manner. METHODS: Two approaches
are proposed to achieve high dose inhomogeneity: (1) implicitly reduce dose
uniformity by increasing the error tolerance for the PTV; (2) explicitly add
specific localized information by introducing the structure, located at 5 mm to 1
cm inside the PTV, and prescribe a higher dose. We formulate the inverse planning
problem in a total-variation minimization framework to reduce the complexity of
the fluence maps. The optimization problem was solved with a fast and efficient
first-order method called TFOCS. For validation, 15-beam IMRT plans were
generated for a lung SBRT case, where normal tissue constrains are directly taken
from the RTOG lung SBRT protocol 0915. The inhomogeneous plans generated from the
two approaches were compared with a homogeneous plan in terms of dose
distributions. RESULTS: Both inhomogenous plans delivered higher doses to the
target compared with the homogenous plan, with a ~10% increase in max dose. The
implicit approach increased the high dose spillage (outside PTV) to 0.52%,
leading to more tissue damage. On the other hand, the explicit approach
maintained the high dose spillage at a lower level of 0.18%, similar to that of
the homogenous plan. Moreover, with local information of the PTV, the explicit
approach allocated the hot spots around the center of the PTV, ensuring the
safety and effectiveness of SBRT. CONCLUSIONS: The proposed method using specific
localized information inside the PTV can safely and effectively deliver high
doses to the target and lead to improved local control.
PMID- 28517501
TI - SU-E-T-625: Robustness Evaluation and Robust Optimization of IMPT Plans Based on
Per-Voxel Standard Deviation of Dose Distributions.
AB - PURPOSE: Proton dose distributions, IMPT in particular, are highly sensitive to
setup and range uncertainties. We report a novel method, based on per-voxel
standard deviation (SD) of dose distributions, to evaluate the robustness of
proton plans and to robustly optimize IMPT plans to render them less sensitive to
uncertainties. METHODS: For each optimization iteration, nine dose distributions
are computed - the nominal one, and one each for +/- setup uncertainties along x,
y and z axes and for +/- range uncertainty. SD of dose in each voxel is used to
create SD-volume histogram (SVH) for each structure. SVH may be considered a
quantitative representation of the robustness of the dose distribution. For
optimization, the desired robustness may be specified in terms of an SD-volume
(SV) constraint on the CTV and incorporated as a term in the objective function.
Results of optimization with and without this constraint were compared in terms
of plan optimality and robustness using the so called'worst case' dose
distributions; which are obtained by assigning the lowest among the nine doses to
each voxel in the clinical target volume (CTV) and the highest to normal tissue
voxels outside the CTV. The SVH curve and the area under it for each structure
were used as quantitative measures of robustness. Penalty parameter of SV
constraint may be varied to control the tradeoff between robustness and plan
optimality. We applied these methods to one case each of H&N and lung. RESULTS:
In both cases, we found that imposing SV constraint improved plan robustness but
at the cost of normal tissue sparing. CONCLUSIONS: SVH-based optimization and
evaluation is an effective tool for robustness evaluation and robust optimization
of IMPT plans. Studies need to be conducted to test the methods for larger
cohorts of patients and for other sites. This research is supported by National
Cancer Institute (NCI) grant P01CA021239, the University Cancer Foundation via
the Institutional Research Grant program at the University of Texas MD Anderson
Cancer Center, and MD Andersona?TMs cancer center support grant CA016672.
PMID- 28517500
TI - SU-F-BRCD-06: Multiple Anatomy Optimization of Accumulated Dose.
AB - PURPOSE: Multiple anatomy optimization (MAO) utilizing deformable dose
accumulation on entire 4DCT data sets is implemented to overcome ambiguity
between optimal dose defined on a single anatomy and optimal accumulated dose
resulting from dose delivery to moving and deforming anatomy. METHODS: Six lung
cancer patients are planned using two methods of radiotherapy optimization: the
internal target volume (ITV) envelope method and MAO, which simultaneously
optimizes a single fluence for delivery to all 10 breathing phases such that the
accumulated dose satisfies the plan objectives. Target dose is constrained to 70
Gy. The ITV-plan is optimized on a single breathing phase with the planning
target volume defined as the ITV; the MAO target is the moving CTV. MAO is
compared to single image ITV optimization based on the accumulated dose assuming
equal monitor-units to each phase. Dose-volume differences between single image
estimations and 10-image accumulation are examined. RESULTS: Single image optimal
dose distributions overestimate target V70 by 4.2%+/-3.1% (average, one standard
deviation) and in five of six cases ipsilateral lung V20 is underestimated
(1.4%+/-0.9%). For these five cases, MAO increases V70 by 2.8%+/-2.5% (maximum of
6% increase in V70) and reduces ipsilateral lung V20 by up to 3% (average
decrease of 1.2%+/-1.3%). Contralateral lung V20, esophagus V25, and heart V30
are also reduced by up to 5%, 3%, and 3%. For the sixth case, lung tumor motion
is on the order of the dose voxel size (3mm), and MAO did not improve upon the
ITV plan. CONCLUSIONS: Dose-volume optimization on a stationary image does not
ensure accumulated dose coverage to the moving CTV. Multiple anatomy optimization
can remove dose ambiguity and improve plan quality. P01CA11602 and Philips
Medical Systems.
PMID- 28517502
TI - MO-A-213AB-03: Commissioning of a Clinical Chair for Patients Treated in the
Seated Position Using an Inclined Beam Line Treatment Room.
AB - PURPOSES: A chair, coupled to a robotic patient positioning system (PPS) was
manufactured to treat an intracranial tumor in a proton incline beam-line system.
Treating patients in the seated position as accurately and efficiently as a
treatment table requires the essential functions of isocentric rotation and a
weight-sagging-correction algorithm for positioning patients in the seated
position. METHODS AND MATERIALS: The chair design incorporated a down-slope arm
to achieve the desired beam-line height. To overcome this limitation of only 125
degree rotation on PPS, five indexed positions of the seat-base-plate (SBP) were
implemented. An in-house developed optical tracking system using a six degree-of
freedom optical camera system was used to align the treatment room coordinate
system with the chair coordinate system at all SBP positions. Furthermore, this
optical tracking system quantified the sagging effect due to both the height and
weight of a variety of patients. RESULTS: The optical tracking system can measure
accuracy of 0.1 degree and 0.1 mm. The SBP rotating axis was aligned within 0.1
degree to PPS rotating axis. A residual precession of chair rotation was found to
be an ellipse with long axis of 2.0 mm and short axis of 1.0 mm. An additional
0.75 mm deviation occurred between rotating of SBP and PPS axes. Sagging tilt of
0.6 degree was found on the SBP for the home position for every additional 162
lbs load. This resulted in a 1.1cm shift (0.65 cm forward and 0.87 cm) for an
isocenter 90 cm away from the SBP plate. CONCLUSIONS: Using in-house developed
optical tracking system, the overall maximum displacement of treatment chair
system from isocenter is within 3.0 mm with known sagging characteristics. This
characterization is essential to reduce the total treatment time and limited the
number of X-rays required for accurate patient alignment in the seated position.
PMID- 28517503
TI - SU-E-T-637: 4D-VMAT Vs. Gated VMAT in Lung Cancer SBRT.
AB - PURPOSE: To assess plan quality and treatment efficiency of 4D-VMAT and gated
VMAT in the treatment of non-small cell lung cancer using SBRT. METHODS:
Treatment planning software was developed in Matlab to simulate both 4D-VMAT and
gated-VMAT on patients with stage I lung cancer and at least 1 cm of tumour
motion. Gated-VMAT delivers radiation to the tumour during only a portion of the
respiratory cycle and hence requires frequent start and stop motions of the
gantry. In the 4D-VMAT algorithm, target and organ motion from the entire
respiratory cycle is incorporated during optimization. Gantry moves continuously
but delivery of each MLC aperture is synchronized to specific phases of target
motion. All 4D-CT scan consisted of 10 phases and were acquired with the patients
breathing freely. The SBRT fractionation scheme was 48 Gy in 4 fractions with at
least 95% of the PTV receiving 100% of the prescription dose. For gated-VMAT, the
PTV was derived from the ITV of the relevant respiratory phases plus a 5mm
margin. In the 4D VMAT algorithm, the GTV was defined on a single phase and the
PTV created with a 5mm margin. PTVs for the other respiratory phases were
determined through 4D-image registration and deformation using a bspline
transformation model. For both treatment deliveries, dose was accumulated on the
maximum exhale phase and DVHs generated. RESULTS: Findings show gated-VMAT and 4D
VMAT deliveries resulted in maximum doses to most OARs far below SBRT protocol
constraints. The 4D-VMAT beam on time is on average 8 min. Gated-VMAT will have
similar beam on time but treatment time can more than double after accounting for
25 to 35 beam interruptions per arc. CONCLUSIONS: Gated-VMAT and 4D-VMAT were
able to produce dosimetrically acceptable lung SBRT plans. The advantage of 4D
VMAT is the greater efficiency in treatment delivery.
PMID- 28517504
TI - MO-A-BRB-03: A Clinical Review of the Dosimetric and Temporal Impact of
Unflattened X- Ray Beams.
AB - : Since July of 2005, the University of Iowa has been using a conventional linear
accelerator with the flattening filter removed. This presentation will focus on
the factors affecting the dosimetric accuracy and total delivery time reduction
found clinically of radiation therapy with an unfiattened beam, focusing on
standard fractionation IMRT of the head and neck, as well as gated and hypo
fractionated liver and lung cancer treatments. The dosimetric accuracy of the
unfiattened beam depends on the planning system beam model, which will be briefly
reviewed. The technique used to adjust the beam quality to become equivalent with
a beam utilizing the flattening filter, as well as the approach to define the
field size for these beams will be described. Finally, the short-term beam
stability (< 250 msec) for small MU IMRT and gated delivery will be
characterized, along with the long-term stability from the last 5-years of
clinical daily quality assurance records. LEARNING OBJECTIVES: 1. Understand
technique for matching beam quality of unfiattened and flattened beams. 2.
Understand definition of field size and beam characteristics during initial 200
msecs. 3. Review improved dosimetric accuracy and temporal advantages of
unfiattened beams in clinical use.
PMID- 28517505
TI - SU-E-T-648: Comparison of VMAT Vs Arc Treatment Plans for Patients Undergoing
SBRT of Early-Stage Non-Small Cell Lung Cancer (NSCLC).
AB - PURPOSE: To evaluate the dosimetric implications of using VMAT (Volume Modulated
Arc Therapy) treatment planning techniques compared to traditional Arc therapy
methods for patients undergoing SBRT (Stereotactic Body Radiation Therapy) for
early-stage Non-Small Cell Lung Cancer (NSCLC). METHODS: Ten NSCLC cancer
patients are planned with both VMAT and Arc techniques. The SBRT treatment plans
comparison was quantified by several Dose-Volume Histogram (DVH) indicators
including mean, maximum and minimum doses for GTV, ITV, PTV, OAR (Organs At
Risk), and V95 (volume receiving at least 95% of the prescribed dose) for PTV.
RESULTS: On average VMAT plans require for treatment delivery 16.6 +/- 20.2 %
more monitor units (MU) than the traditional Arc plans. The average PTV minimum,
maximum and mean doses as a percentage of prescribed dose are 94.5 +/- 3.9 %,
114.1 +/- 3.3 % and 106.6 +/- 1.6 % for VMAT vs 91.6 +/- 4.4 %, 119.5 +/- 5.3 %
and 109.5 +/- 2.5 % for the Arc technique. The V95 PTV coverage for VMAT plans
range from 99.4 % to 100 % with a mean of 99.7 %, compared with a range of 96.8 %
to 100 % with a mean of 99 % for the Arc plans. The maximum dose received by the
lungs, spinal cord and chest wall show on average significant increases for Arc
plans as opposed to VMAT plans (5.7 +/- 6 % increase for lungs, 4.4 +/- 9.2 % for
cord and 2.4 +/- 6.3 % for chest wall). The average mean doses and minimum doses
for the OAR are similar for both techniques. CONCLUSIONS: The comparison of VMAT
vs Arc plans for SBRT of NSCLC patients is subject to many variables, including
GTV and PTV volume sizes, shape and their proximity relative to the OAR.
PMID- 28517506
TI - SU-E-T-618: Error Compensated Sparse Optimization for Fast Radiosurgery Treatment
Planning.
AB - PURPOSE: Radiosurgical treatment planning requires a good approximation of the
dose distribution which is typically computed on a high resolution grid. However,
the resulting optimization problem is large, and leads to substantial runtime. We
study a sparse grid approach, for which we estimate and compensate for the
expected deviations from the bounds. METHODS: We buildup an estimate of the
hotspot error distribution by measuring the maximum dose deviation within a voxel
for a large number of randomly generated beam configurations. This results in a
conservative estimation of overdosage as a function of upper bound reduction for
different grid sizes. We adjust the bounds for voxels inside the target volume
(PTV) according to our estimation thus maintaining the likelihood of dose
deviations within acceptable limits. The approach was applied to a prostate case,
where the volumes of interest are large and close to each other. Our planning
objective is a prescribed dose of 36.25 Gy to the 87% isodose. We employed
constrained optimization to optimize the lower PTV bound on 2, 4, and 8mm
isotropic grids. Results were computed on 1mm grid. RESULTS: The initial coverage
was 93.7%, 92%, and 91%, and the volume exceeding the upper bound was 0.74%,
1.71%, and 9% for grid sizes of 2, 4, and 8mm, respectively. Changing the upper
bound by 0.5% and 2.5% for the 4 and 8 mm grids resulted in only 0.75% and 2.2%
of the volume exceeding the bound. The coverage did not change. Mean optimization
times were 141.1, 22.6 and 3.4 minutes using the 2, 4 or 8mm grid, respectively.
CONCLUSIONS: Experiments show that planning on a sparse grid can achieve
comparable results with those of a high resolution grid, as long as the bounds
are carefully balanced. This leads to substantially lower optimization times
which facilitates interactive planning. This work was supported by the Graduate
School for Computing in Medicine and Life Sciences funded by Germanya?TMs
Excellence Initiative [DFG GSC 235/1].
PMID- 28517507
TI - SU-E-T-630: MCO-Informed VMAT Planning for Prostate Cancer.
AB - PURPOSE: To develop a VMAT optimization procedure using information from Multi
Criteria Optimization of IMRT plans and to perform a treatment planning
comparison for prostate cancer patients. METHODS: IMRT plans using Multi-Criteria
Optimization (MCO), 6 MV photons, 20 and 7 treatment fields were generated for 10
prostate patients in the RayStation treatment planning system (Version 2.2.13,
Raysearch Laboratories, Stockholm, Sweden). The prescription dose was 7560 cGy to
the prostate PTV and 5796 cGy to the seminal vesicles, using a simultaneous
integrated boost technique. The resulting DVH parameters of the 20 field IMRT-MCO
plan were used as initial optimization parameters for VMAT planning. The initial
VMAT plan for each patient was further optimized by adjusting the optimization
objectives/constraints. Final plan quality was compared using a homogeneity index
(HI) and D98 for PTV-prostate, V70 and V75 for anterior rectum and V70 for
bladder. Moreover, delivery efficiency of VMAT and the 7 field MCO-IMRT plans was
also evaluated. RESULTS: All plans fulfilled the standard clinical objectives.
The average HI of the PTV-prostate was 0.11 for VMAT, 0.13 for 20 field IMRT-MCO
and 0.12 for 7 field IMRT-MCO, respectively. Average D98 values were 7191, 7294
and 7305 cGy for VMAT, 20 field IMRT-MCO and 7 field IMRT-MCO, respectively. For
organ-at-risk (OAR), V70 and V75 for anterior rectum and V70 for bladder were
within 3%. Analysis of delivery efficiency shows the estimated delivery time of
VMAT is less than 2 minutes, while it is 7 min for 7 field IMRT-MCO. CONCLUSIONS:
MCO-informed VMAT optimization is a useful way to generate optimal VMAT plans.
The resulting VMAT plan quality essentially matched the MCO-IMRT plan but with a
shorter delivery time. Dose homogeneity of VMAT is slight superior compared to
IMRT-MCO while the cold spots are slightly inferior. Furthermore, there is no
clinically significant difference in OAR sparing. Funding support provided by NCI
Federal Share Proton Beam Program Income Grant and Raysearch Laboratories.
PMID- 28517508
TI - MO-A-213AB-07: Evaluation of Distal Dose Surface with In-Room PET for Proton
Therapy Monitoring.
AB - PURPOSE: The objective of this study is to evaluate the feasibility of proton
beam treatment verification using in-room PET. As of February 2012, four patients
have been studied in a clinical trial. In addition, we suggest a new method
comparing the distal surface of the measured and simulated PET activities to
verify the location of the distal dose surface. METHODS: Patients were scanned
for 20 minutes with an in-room PET positioned next to the proton treatment head
in a gantry room for beam delivery using passive scattering. The time between end
of treatment and the start of the scan was within about 2 minutes. The predicted
distribution of the PET activities and the proton dose distributions in the
patients were also calculated using Monte Carlo (MC). Along the beam direction,
the 50% fall-off positions of the maximum PET activity at each line profile were
compared with the MC simulated and the measured PET images, and then the
differences were assessed with root-mean-square deviation (RMSD) and mapped in
the beam's eye view. RESULTS: The measured PET images showed a good spatial
correlation with the simulated PET images and the proton dose distributions even
though the treated volumes and locations varied between patients. The RMSD
values, representing the surface differences between the measured and simulated
PET, were assessed to be 4.3-5.1 mm for four patients. Some region including the
penumbra showed larger differences but was excluded. CONCLUSIONS: We have
explored the potential of the in-room PET for proton therapy monitoring through a
clinical trial. The PET image analysis method based on MC simulations showed that
the distal dose surface could be determined within a few millimeters but not
within the aimed accuracy of 2-3 mm. Improvements in PET-CT image registration
and biological washout modeling will most likely increase the accuracy further.
NIH/NCI P01 CA021239.
PMID- 28517509
TI - SU-E-T-620: Computational Boundary Sampling to Accelerate IMRT Optimization.
AB - PURPOSE: To reduce the time and memory requirements of Intensity Modulated
Radiation Therapy (IMRT) treatment planning. METHODS: We propose a new sampling
method, called Computational Boundary Sampling (CBS) for IMRT optimization, which
samples all the boundary voxels and a certain percentage of inner voxels of each
region of interest (ROI). Within CBS, we developed a grid-based sampling method
for choosing inner voxels. In this method, each region is first evenly gridded
and then sampling points are randomly selected from each sub-volume. We also
developed a supporting theory to quantify the solution quality of CBS. We
compared a variant of CBS that always keeps boundary voxels and a variant of CBS
that does not. Finally, we quantified the impact of CBS on 10 different
anonymized, clinical treatment cases using a prioritized prescription
optimization method, including compute time, required memory and objective
function values. RESULTS: (1) We have found that the D95 of the targets are
generally 4% larger when boundary voxels are included. (2) Grid sampling,
compared to completely random sampling, yields more uniformly distributed
sampling, with better solution quality, and less variance between independent
runs, using the same or less time. (3) We have compared our original IMRT
optimization solver without sampling and the solver combined with CBS sampling.
The result showed that CBS can reduce the solution time and memory consumption by
up to 20x with < 2% change in dosimetric variables. CONCLUSIONS: We have proposed
a new sampling method (CBS), along with corresponding new techniques including
boundary sampling and grid sampling, to improve time and space efficiency of IMRT
optimization. A corresponding theory is developed to quantify the error bound.
Experimental results have shown that our new methods significantly reduce
solution time and memory costs with negligible impact on resulting plan quality.
PMID- 28517510
TI - MO-A-217BCD-01: Internal Emitter Dose Estimation.
AB - : Tissue absorbed dose (D) is a computed result for internal emitters. For fixed
geometries, D is calculated by a matrix (S) multiplication of the integrated
activity vector (A). The last quantity is usually measured by nuclear imaging of
activity in various source organs and performing a temporal integration. A is the
same as the total number of source decays. Dose is computed for a number of
target organs - some of which will be the same as the source organs. The D = S*A
relationship is general in that the same formula may also be used for voxels
within organs or even down to the cellular level. Finding the activity (A) in
source tissues may be done by a number of methods of which 6 are described. The
most common clinical technique is the geometric mean (GM) image of an organ.
Uncertainties in the GM method are ~ +/- 30%. If one can do quantitative SPECT,
PET or CAMI imaging, the variation is reduced to around +/- 6%. These last three
techniques, however, require fusion of anatomic (e.g. CT) and nuclear images. The
S matrix is generated via Monte Carlo methods and may be used in two formats. The
most common is a set of phantom-derived values for regulatory or scientific
considerations. An example is the OLINDA program from Vanderbilt University. In
this case, the corresponding animal or patient A value must be normalized using
blood flow arguments. A second format is modification of a phantom's S values for
a particular patient using the latter's geometry as found in CT or MRI scans.
Corrections in such cases may be 2-fold or more because of patient organ size
variability. These variations may be due to genetic reasons and/or disease. Two
caveats to the use of the above dose formulation should be mentioned. One
exception is that the geometry may vary during tissue irradiation; e.g., by tumor
size decrease due to immediate radiation dose effects. In this case, the standard
formula is replaced by its differential form: dD/dt = S(t)*A(t). Dose rate may
also be an important biological factor in assessing tissue response. A second
important biological consideration is that effects - such as tumor regression -
may depend upon higher powers of D than the first. Thus, the tissue response may
not be a linear function of D, but would exhibit a sigmoid shape. One would
anticipate such responses due to saturation of a biological system. LEARNING
OBJECTIVES: 1. Knowing the general formula for internal emitter absorbed dose
estimation. 2. Understanding the various methods used to measure activity, at
depth, in source organs in a living animal or patient. 3. Realizing that two
types of dose may be computed: one for a phantom and a second type for an
individual patient. S values must be modified accordingly for these two
computations. 4. Estimating uncertainties - including those in both A and S -
involved in the dose estimation process.
PMID- 28517511
TI - SU-E-T-632: Metrics for Comparing Dose Volume Histograms.
AB - PURPOSE: The process of IMRT planning is an iterative inverse process, where a
planner seeks to attain a desired dose distribution, specified for tumors and
OARs, hence creating a plethora of competing constraints. However, the final
product is rather the unpredictable outcome of a series of trial-and-error
attempts at meeting these competing objectives. A key tool to inspect the quality
of a plan is the DVH. We provide a set of metrics for unbiased DVH comparison.
METHODS: The treatment of one prostate case was planned by seven planners, while
imposing the same clinical objectives for PTV and OARs. The resulting seven DVHs
were compared based on their deviation of from the ideal coverage, namely 100% of
PTV receiving 100% of the dose. Our deviation function L measures the area
between the ideal and realized DVH. A weight function W is used for dose
dependency. We employ a set of Ws: constant, piece-wise linear, quadratic, normal
and beta-distributional. RESULTS: We show that the deviation of some planners are
consistently higher than others for all eight Ws. Similarly, we observe that one
of the planners consistently exhibits the lowest deviation, while another one is
low for linear and quadratic Ws and worsen for the distributional functions
independent of their slope and range. Further, the normal and beta-density
function weights, as they primarily penalize the range of 95% < Dose < 105%,
hence discriminating only deviations in the respective region. CONCLUSIONS: The
outcome of treatment planning is strongly related to the planning personal. The
proposed set of DVH metrics allow for unbiased comparison, beyond the visual
inspections. An optimized superposition of these metrics may yield a practical
tool for daily treatment planning. Furthermore, these results exhibit the need
for methods whose outcomes are independent of the planning personal.
PMID- 28517512
TI - MO-A-213AB-09: Hypofractionated Proton Therapy of the Prostate: The Impact of the
Uncertainties in Dose Delivery and Alpha/Beta Ratio on Tumor Dose Escalation.
AB - PURPOSE: Hypofractionation is expected to improve therapeutic ratio for prostate
radiotherapy, due to the relatively low alpha/beta ratio of the prostate tumor
(~1.2 to 2.0 Gy). However, the gain in tumor equivalent dose in 2-Gy fractions
(EQD2) is accompanied by the increased uncertainty in delivered dose due to inter
fractional variations. The purpose of this study is to evaluate how this trade
off is affected by the uncertainty of the tumor alpha/beta. METHODS: We used
serial CT images acquired from two prostate cancer patients. Target and normal
organs were contoured on the simulation and daily images. A 3D conformal proton
plan was designed based on standard fractionation (78 Gy in 39 fractions) and
renormalized for hypofractionation (between 5 and 28 fractions). The fraction
size of the hypofractionated protocols was adjusted so as to maintain the maximum
rectal dose at 78 Gy-EQD2 (alpha/beta = 3 Gy). The fractional dose, calculated on
each daily CT, was mapped to the simulation geometry via deformable registration.
The worst-case-scenario PTV dose for a hypofractionated protocol was estimated by
summing the fractions (e.g., 28) with the lowest D97%. The target dose (e.g.,
D100%) was evaluated for alpha/beta of 1.2 to 2.0 Gy. RESULTS: The dose delivery
uncertainty due to inter-fractional motion increased as the treatment became more
hypofractionated. D100% was<78 Gy-EQD2 for protocols with 28, 26, 23 and 20
fractions when alpha/beta was >1.25, 1.46, 1.68 and 1.84 Gy, respectively. At
alpha/beta of 2 Gy (1.2 Gy), D99% ranged from ~79 (81) to 85 (98) Gy-EQD2 for
treatments in 28 to 5 fractions. Below D97%, the target dose was predominantly
determined by alpha/beta, and the motion impact was minimal. CONCLUSIONS: In
prostate treatments, the impact of inter-fractional motion on tumor dose
escalation is small for alpha/beta <2.0 Gy, and is of minimal concern to
hypofractionated proton therapy. This study was supported by the Federal Share of
program income earned by Massachusetts General Hospital on C06-CA059267, Proton
Therapy Research and Treatment Center.
PMID- 28517513
TI - SU-E-T-643: Optimum Beam Parameters for Lung SBRT Volumetric Arc Treatment.
AB - PURPOSE: We present an analysis of the variation in acceptable SBRT lung plans
with beam parameters. A figure of merit encompassing standard metrics is used for
analytical comparison to determine the optimum plan quality. METHODS: A set of
optimization dose-volume constraints was formulated that consistently produced
acceptable plans. Plans were normalized to deliver a prescription dose (PD) of
5000 cGy to 95% of the PTV volume. The Conformity Index (CI), Conformity Number
(CN), and Gradient Index (GI), and mean GTV dose (MDgtv) were calculated. In SBRT
hotspots near the target center are often deemed acceptable. The ratio MDgtv/PD
is greater then 1.0 and larger values indicate that more dose is delivered where
desired within the PTV. We combine the indices into a single figure of merit, FOM
= (1/CI)*CN*(1/GI)*(MDgtv/PD), for which larger values indicate better plan
quality dosimetrically. FOM values were normalized to 1.0 for the best plan.
Twenty four plans were calculated for 6X, 6X flattening filter free (FFF), 10X,
and 10X FFF photon beams. The gantry arc rotations were 0 degrees -180 degrees
(180arc), 135 degrees -30 degrees (255arc), and 181 degrees -179 degrees
(360arc). The couch angle was either 0 degrees (coplanar) or +/- 15 degrees
(non-coplanar). RESULTS: For the normal lung volume there was no significant
variation in either mean dose or percent volume receiving 2000 cGy. However, the
percent volume receiving 500 cGy varies significantly with energy and couch
angle. Ninety six plan quality indices were tabulated. Overall, the 6X FFF non
coplanar beam with a 255 degree arc gave the best the figure of merit; it was
6.5% higher then nearest competitor largely due to superior conformality.
CONCLUSIONS: Individual plan quality indices were combined into a single figure
of merit for various beam parameters that can be used to analytically select the
optimum dosimetric plan.
PMID- 28517514
TI - SU-F-BRCD-05: Mean Regional Dose to the Esophagus Predicts Acute Toxicity Rate
for Lung Cancer Patients.
AB - PURPOSE: The relationship between spatial aspects of the dose distribution and
incidence of acute radiation esophagitis for non-small-cell lung cancer (NSCLC)
patients is not well understood. Specifically, the location of dose along the
superior-inferior (SI) axis of the esophagus has not been previously considered.
We introduce the concept of mean regional dose (MRD) calculated for esophageal
subvolumes, and test for significance for prediction of acute esophagitis (AE).
METHODS: The 3D dose distribution within the esophagus was extracted for 541
NSCLC patients treated with definitive photon therapy. The esophagus contour was
divided into equal geometric halves, thirds, and fourths along the SI direction
of the structure. MRD in each subvolume was calculated. Univariate logistic
regression was performed to determine the correlation between MRD and CTCAE3.0 AE
grade = 2 (medical intervention). The MRD was incorporated into an existing NTCP
model (based on mean dose for the total esophageal volume) as a separate additive
factor. RESULTS: Univariate analysis indicated a significant correlation between
AE grade = 2 and MRD in each of the esophageal subvolumes except for the inferior
third and inferior-most quarter. There was a statistically significant
improvement when including the additive MRD factor for the superior/inferior
halves, superior/inferior thirds, and superior-most/inferior-most quarters into
the NTCP model. CONCLUSIONS: This study investigates previously unexplored
regional differences in delivered dose to the esophagus of patients treated for
NSCLC. There is evidence to suggest that dose to the superior portions of the
esophagus is more important as it relates to the potential for acute toxicity.
The 541 patient cohort is the largest database used to investigate AE in patients
treated for NSCLC, strengthening the power of the statistical results. Additional
methods to incorporate dose in individual esophagus voxels (along the SI axis)
into the NTCP model are also being explored.
PMID- 28517515
TI - SU-E-T-624: Comparison of PTV+PRV-Based Optimization and Robust Optimization in
Intensity-Modulated Proton Therapy.
AB - PURPOSE: Robust optimization leads to IMPT plans that are more robust than and
superior in optimality compared to PTV-based optimized plans. Robust optimization
incorporates setup and range uncertainties, which implicitly adds margins to
targets and organs-at-risk (OARs); whereas PTV-based optimization only considers
setup uncertainties and adds margins only to targets in practice. The purpose of
this work is to determine if the superiority of robustly optimized plans is due
to not assigning margins to OARs during PTV-based optimization. METHODS: Plan
robustness and optimality of the PTV plus Planning organs-at-Risk Volume (PRVs)
based plans and robustly optimized plans were compared for 5 head and neck cancer
cases and one rhabdomyosarcoma case. The PRVs were generated by expansion from
OARs by 3 mm. 9 different dose distributions were computed - one each for +/-
setup uncertainties along three spatial directions, for +/- range uncertainty,
and the nominal dose distribution. The worst-case dose distribution was obtained
by assigning the lowest dose among the 9 doses to each voxel in the target and
the highest dose to each voxel outside the target. The DVHs from the worst-case
dose were used to assess the plan optimality and robustness. D1cc doses for
spinal cord and brainstem, mean doses Dmean for oral cavity and parotids, and D1%
doses for other organs were also used to assess plan optimality. D5% and D95%
doses are used to assess target dose coverage and homogeneity. RESULTS: For H&N
cases, PTV+PRV-based optimization was inferior to robust optimization. However,
PTV+PRV-based optimization yielded plans that spared OARs better than PTV-based
optimization, although the target dose robustness and homogeneity were comparable
to the PTV-based optimization. The same conclusions are also valid in the
rhabdomyosarcoma case. CONCLUSIONS: We find that the PTV+PRV method can partly
improve plan optimality, but it is still inferior to robust optimization method.
This research is supported by National Cancer Institute (NCI) grant P01CA021239,
the University Cancer Foundation via the Institutional Research Grant program at
the University of Texas MD Anderson Cancer Center, and MD Andersona?TMs cancer
center support grant CA016672.
PMID- 28517516
TI - MO-A-213AB-02: Redesign of a 6 MV Linear Accelerator Waveguide to Produce
Energies Up to 10 MV.
AB - PURPOSE: To investigate the feasibility of producing a short, high-energy linear
accelerator for use in a proposed hybrid linear accelerator magnetic resonance
imager (linac-MRI). METHODS: A short 6MV waveguide was previously simulated in
COMSOL and benchmarked against experiment. The simulated input power is increased
from 2.5 to 7.5 MW to reflect replacing the magnetron power source with a
commercially available klystron, and the RF fields within the waveguide are
calculated. The RF solution is used as an input into PARMELA, an electron
tracking software, to calculate the electron energy and spatial distribution
exiting the waveguide. The electric fields within the waveguide are compared with
experimental thresholds for electric breakdown within the waveguide to determine
the possibility of operation at increased input power. The energy spectrum of the
electron beam incident on the target is analyzed for suitability for
radiotherapy. Finally, some potential modifications to the simulated cavity
dimensions and positioning are discussed, and a preliminary estimate of the
effects on the electron distributions are analyzed. RESULTS: When the input power
is increased, peak surface electric fields within the waveguide of 215 MV/m are
calculated, below the threshold determined by experiment of 240 - 300 MV/m for
similar resonant structures. The FWHM of the electron focal spot is shown to be
1.5 times larger than the focal spot from the unmodified waveguide. The maximum
electron energy increases from 6.1 to 10.6 MeV and the spread of electron
energies is 5 times larger than the original. The modifications to the first
cavity are shown to reduce the focal spot and energy spread to be comparable to
the unmodified waveguide. CONCLUSIONS: It is feasible to produce a high-energy
waveguide that is short enough for use in our linac-MRI. Slight modifications to
the existing waveguide design will be required to optimize beam parameters for
treatment. ACF Graduate Studentship.
PMID- 28517517
TI - SU-E-T-636: Comparison of RapidArc-Based Radiosurgery with Cone-Based Cyberknife
Treatment for Multiple Intracranial Tumors.
AB - PURPOSE: To investigate the feasibility of RapidArc technique on intracranial
radiosurgery for multiple lesions. METHODS: Six patients who were previously
treated using cone-based technique, Cyberknife were included in this study. These
patients have multiple lesions (6-9, mostly metastasis). In our current clinical
practice, each lesion was planned and treated individually. The prescription was
15-21 Gy at 80% with single fraction. These cases were replanned with RapidArc on
the platform of Varian Truebeam STx equipped with high resolution MLC leaves of
2.5mm at center. The maximum dose rate is 1400 MU/min at 6 MV for flattering
filter free mode. Because of long span of multiple lesions, the targets were
divided into two groups with two isocenters. Each plan with one isocenter
contains 4 non-coplanar arcs, and dose optimization was performed with the two
plans combined. Critical organs, such as eyes, brainstem and brain were
constrained. The individual Cyberknife plans were summed to compare with the
RapidArc plan. Scenarios of setup error were simulated during RapidArc treatment.
RESULTS: RapidArc plans can achieve comparable target coverage and normal tissue
avoidance to Cyberknife plans. The brain dose volume histogram (DVH) curves of
the two techniques are similar in spite of different appearance of their 3D dose
distributions. MU is much higher for summed Cyberknife plan. Because RapidArc can
treat several lesions together, the complete treatment time for all lesions is
significantly reduced. However RapidArc treatment is susceptible to setup error,
which may cause increase in normal tissue dose and decrease in target dose
coverage. The level of discrepancy depends on the magnitude of setup error,
location and dose distribution of the target. CONCLUSION: Multiple brain lesions
treatment with RapidArc radiosurgery is clinically feasible with setup error
fully accounted. It can provide dose performance comparable to cone-based
Cyberknife treatment.
PMID- 28517518
TI - MO-A-BRB-02: Facts and Fiction of Flattening Filter Free (FF-FFF) X-Rays Beams.
AB - : The primary purpose of the FFF X-rays is to provide much higher dose rates
available for treatments. For example, FFF X-rays from Varian TrueBEAM can
deliver 1400 MU/minute for 6 MV X-rays and 2400 MU/minutes for 10 MV X-rays.
Higher dose rates have definite clinical benefits in organ motion management. For
example, larger dose fractions can be delivered in a single breath-hold or gated
portion of a breathing cycle. In SRS or SBRT treatments, large MUs are often
required and FFF X-ray beams can deliver these large MUs in much shorter "beam
on" time. With shorten treatment time, these FFF X-rays improve patient comfort
and dose delivery accuracy. FFF X-ray beams may become one of the necessary
equipment configurations for SBRT and/or SRS treatments, in the future. This
presentation will address some unique issues dealing with the FFF X-rays: (1)
FIELD SIZES flattening Filter Free (FFF) X-ray beam has been in clinical use for
quite some time. However, not until recently, these FFF beams are used in
limited, small field sizes, for example, in Tomotherapy and CyberKnife
machines.Varian TrueBEAM allows the FFF X-ray beam to have up to 40 * 40 cm field
sizes for both 6 and 10 MV X-rays (15 MV FFF X-rays are not yet released for
clinical use). For large treatment fields, the dose uniformity within an
irradiated treatment field will need to be "modulated" by MLC movements (IMRT) to
cut down the higher beam intensity near the central portion of the FFF X-ray
beam. Thus, larger MUs are required compared with a conventional (flattened) X
ray beam. Or, MLC movements (EVIRT) are now being used to "flatten" the FFF X
rays to provide dose uniformity within those large PTVs. The high dose rates from
the FFF X-rays are now being off-set by the larger MUs requirements. Therefore,
FFF X-rays can bring clinical advantages over conventional X-rays when used with
small field sizes, such as in SBRT and/or SRS applications. (2) DOSEVIETRY
MEASUREMENT EQUIMENT: Because of the more than 2 to 4 fold increases in dose rate
(MU/minute), the radiation measurement equipment and techniques need to be
carefully evaluated, such as ionization chamber characteristics, electrometers,
scanning equipment. First comes to mind is the ion-recombination characteristics
of the ionization chamber (P-ion). This will determine the accuracies of the
measured percentage depth doses and penumbra of these FFF X-ray fields. And, it
will also affect the absolute dose measurements (Gy/MU) using the TG-51
formulations. The measured PDDs and profiles should be corrected for the P-ion
effect. However, it is not a simple task for physicists to perform the P-ion
corrections for PDDs and profiles using the presently available methods
associated in commercial 3-D scanning equipment and algorithm. It may become
necessary for physicists to adapt and get accustom to the use of "standard beam
data" provided by manufacturers in the future. In addition, because of the use of
FFF X-rays are focused on SBRT and/or SRS applications, beam data acquisition,
scanning techniques, and beam modeling are vitally important. There are many
publications addressing the "output factors" from small fields, but none pay
enough attention to the penumbra characteristics of these small X-ray beams.
Because of the proximity to critical organs, the penumbra characteristics of
small fields are often more clinically important than output factors. FFF X-rays
play an important role in SBRT and SRS applications. Therefore, careful penumbra
measurements should be addressed. Again, it may become necessary for physicists
to adapt the use of "standard beam data" provided by manufacturers. (3) RADIO
BIOLOGICAL QUESTION: Though there is a lack of controlled clinical studies with
FFF X-ray beams, there are several scientific articles addressing the
radiobiological concerns of high dose rate deliveries, especially when it is used
to deliver large doses per fraction, such as 10 Gy/faction. This type of dose per
fraction is often used in SBRT or SRS treatments. Radiobiological concerns are
not in the cell kill effect within the target volume. It is the normal tissue
damages surrounding the target. There are concerns about the late toxicities of
these high dose rate and high dose per fraction deliveries using FFF X-ray beams.
(4) SKIN (ENTRANCE) DOSE DISCUSSIONS: In conventional X-ray beams, the low energy
components of the X-ray beam are removed by the in-line X-ray flattening filter.
But, in Flatten Filter Free X-ray beams, these low energy components are exiting
the X-ray collimators. This is clearly documented by the difference in the
percentage depth doses for these FFF X-ray beams. The FFF X-ray beams have a
lower "effective energy" compared to conventional X-rays. Therefore, it is
important to study the skin (entrance) dose from these FFF X-rays. In the
literature, reported skin (entrance) doses from different linear accelerator
manufacturers vary widely. Skin doses from Varian TrueBEAM have been studied and
have found to be marginally higher than the conventional X-rays. However this
margin increase is not clinically significant.(5) Summary / conclusions /
discussions: The FFF X-rays improve the treatment delivery by their very high
dose rates (1400 and 2400 MU/minute) and shortened treatment time. FFF X-ray
beams are most applicable and the high dose rates are most advantageous when the
treatment field sizes are small. The dosimetry of FFF-X-rays is made more complex
by the P-ion determination and necessary corrections to X-ray beam percentage
depth doses and profiles. There are radiobiological concerns about late toxicity
of normal tissue irradiated by FFF X-rays when large dose per faction treatment
applications are used. There are wide ranges of skin doses from these FFF X-rays
reported in the literature. LEARNING OBJECTIVES: 1. Flattening Filter Free X-rays
have been in clinical use for many years but mostly for small field sizes. 2.
Flattening Filter Free X-rays have significantly shorter treatment time if is
used for small field applications, such as: SBRT or SRS. 3. Because of the high
dose rate (MU/minute), dosimetric properties of these FFF X-rays need to be
carefully studied. Ion-recombination of ionization chambers is a concern. Beam
data acquisition, beam modeling, and absolute dosimetry need to be done with
great care, especially in small field applications. 4. Late toxicities of normal
tissue may be a concern and need to be studied by organized clinical protocols.
PMID- 28517519
TI - SU-E-T-647: Plan Quality in Computerized Non-Coplanar IMRT Beam Angle
Optimization is Highly Dependent on the Extent of the Beam direction Search
Space.
AB - PURPOSE: To investigate the relationship between plan quality and the extent of
the beam direction search space in computerized beam angle selection for
generating optimal (non-coplanar) IMRT plans for prostate SBRT with dose
distributions simulating HDR brachytherapy. METHODS: iCycle (1) was used to
investigate the relationship between plan quality and the extent of the set of
beam directions available for plan generation. For a group of 10 prostate
patients, optimal plans were generated for 5 direction search spaces. For
coplanar treatments (CP set), 72 orientations were available for selection
(separation 5 degrees ). The fully non-coplanar set (F-NCP) included the CP
directions plus 430 directions spread over the sphere. The CK set contained the
directions available at the robotic Cyberknife unit. CK+ and CK++ were extensions
of CK to investigate some of its characteristics. Generated plans were in
accordance with our clinical SBRT protocol for Cyberknife treatment, delivering 4
fractions of 9.5 Gy. Adequate PTV coverage had the highest priority. Reduction of
rectum dose was the highest OAR priority. RESULTS: The mean PTV coverage (V95) of
all SBRT plans was 99% i,+/- 0.9% (1 SD). F-NCP plans had most favorable OAR dose
parameters, while for coplanar plans OAR doses were highest. Compared to coplanar
treatment, rectum Dmean/V60 were 25% / 37% and 19% / 21% lower in F-NCP and CK
plans. Higher rectum dose for the Cyberknife set compared to F-NCP was not caused
by a lack of posterior beams for Cyberknife. For all search spaces, reduction in
OAR dose only leveled off with > 20 beams in the plans (for CP, rectum V60 in 25
beam plans was reduced by 64% compared to 11 beams). In the non-coplanar set-ups,
there was a preference for beams with a (large) lateral component. CONCLUSIONS:
Plan quality clearly improved with the extent of the beam direction search space
(coplanar worst), and the number of beam directions in the plan (25 clearly
better than 11).(1) Breedveld S, Storchi P, Voet P, Heijmen B, Med Phys 2012;
DOI: 10.1118/1.3676689.
PMID- 28517520
TI - SU-F-BRCD-09: Total Variation (TV) Based Fast Convergent Iterative CBCT
Reconstruction with GPU Acceleration.
AB - PURPOSE: To improve image quality and reduce imaging dose in CBCT for radiation
therapy applications and to realize near real-time image reconstruction based on
use of a fast convergence iterative algorithm and acceleration by multi-GPUs.
METHODS: An iterative image reconstruction that sought to minimize a weighted
least squares cost function that employed total variation (TV) regularization was
employed to mitigate projection data incompleteness and noise. To achieve rapid
3D image reconstruction (< 1 min), a highly optimized multiple-GPU implementation
of the algorithm was developed. The convergence rate and reconstruction accuracy
were evaluated using a modified 3D Shepp-Logan digital phantom and a Catphan-600
physical phantom. The reconstructed images were compared with the clinical FDK
reconstruction results. RESULTS: Digital phantom studies showed that only 15
iterations and 60 iterations are needed to achieve algorithm convergence for 360
view and 60-view cases, respectively. The RMSE was reduced to 10-4 and 10-2,
respectively, by using 15 iterations for each case. Our algorithm required 5.4s
to complete one iteration for the 60-view case using one Tesla C2075 GPU. The few
view study indicated that our iterative algorithm has great potential to reduce
the imaging dose and preserve good image quality. For the physical Catphan
studies, the images obtained from the iterative algorithm possessed better
spatial resolution and higher SNRs than those obtained from by use of a clinical
FDK reconstruction algorithm. CONCLUSIONS: We have developed a fast convergence
iterative algorithm for CBCT image reconstruction. The developed algorithm
yielded images with better spatial resolution and higher SNR than those produced
by a commercial FDK tool. In addition, from the few-view study, the iterative
algorithm has shown great potential for significantly reducing imaging dose. We
expect that the developed reconstruction approach will facilitate applications
including IGART and patient daily CBCT-based treatment localization.
PMID- 28517521
TI - SU-E-T-628: A Cloud Computing Based Multi-Objective Optimization Method for
Inverse Treatment Planning.
AB - PURPOSE: Multi-objective (MO) plan optimization entails generation of an enormous
number of IMRT or VMAT plans constituting the Pareto surface, which presents a
computationally challenging task. The purpose of this work is to overcome the
hurdle by developing an efficient MO method using emerging cloud computing
platform. METHODS: As a backbone of cloud computing for optimizing inverse
treatment planning, Amazon Elastic Compute Cloud with a master node (17.1 GB
memory, 2 virtual cores, 420 GB instance storage, 64-bit platform) is used. The
master node is able to scale seamlessly a number of working group instances,
called workers, based on the user-defined setting account for MO functions in
clinical setting. Each worker solved the objective function with an efficient
sparse decomposition method. The workers are automatically terminated if there
are finished tasks. The optimized plans are archived to the master node to
generate the Pareto solution set. Three clinical cases have been planned using
the developed MO IMRT and VMAT planning tools to demonstrate the advantages of
the proposed method. RESULTS: The target dose coverage and critical structure
sparing of plans are comparable obtained using the cloud computing platform are
identical to that obtained using desktop PC (Intel Xeon(r) CPU 2.33GHz, 8GB
memory). It is found that the MO planning speeds up the processing of obtaining
the Pareto set substantially for both types of plans. The speedup scales
approximately linearly with the number of nodes used for computing. With the use
of N nodes, the computational time is reduced by the fitting model, 0.2+2.3/N,
with r2>0.99, on average of the cases making real-time MO planning possible.
CONCLUSIONS: A cloud computing infrastructure is developed for MO optimization.
The algorithm substantially improves the speed of inverse plan optimization. The
platform is valuable for both MO planning and future off- or on-line adaptive re
planning.
PMID- 28517522
TI - MO-A-213AB-06: Validation of Nuclear Reaction Models to Simulate Proton Therapy
Range Verification Using Prompt Gamma-Rays.
AB - PURPOSE: The impact of nuclear reaction model differences on simulation of prompt
gamma-ray imaging for proton therapy range verification was assessed. Four
nuclear reaction models were used to simulate gamma emission in proton beams, and
were validated against experimental cross-sections. METHODS: Proton-induced
nuclear reactions on carbon, oxygen, nitrogen and calcium were investigated with
the Monte Carlo toolkits GEANT4 9.5 and MCNPX 2.7, and the dedicated nuclear
reaction codes TALYS 1.4 and EMPIRE 3.1. Absolute cross-sections of discrete
prompt gamma lines and the total gamma production were obtained for the 1-200 MeV
incident proton energy range. They were compared to 34 discrete line measurements
reported in literature. Using these cross-sections, we analyzed the gamma
production along the path of proton beams passing through various tissues.
RESULTS: The differences in absolute discrete line cross-sections as predicted by
the models ranged from almost zero to an order of magnitude, depending on the
gamma line and incident proton energy. Overall, the dedicated nuclear reaction
codes provided a better fit to most experimental excitation functions. For a 150
MeV proton beam stopping in soft tissue, these differences amount to a variation
by a factor of 4 of the gamma emission around the Bragg peak location. The
maximum of gamma production near the end of proton range differed by 7 mm, and
the change of the 50% emission fall-off position was 4 mm. CONCLUSIONS: There is
a clear need for improvement of nuclear reaction models to accurately simulate
proton range verification using prompt gamma-rays. Current simulation codes show
large uncertainties in both the total gamma yield and the correlation of gamma
emission with the proton Bragg peak. GEANT4 and MCNPX in particular appear to
have limited predictive power.
PMID- 28517523
TI - SU-E-T-640: Development of Liver SBRT Planning and Delivery at the Mean
Respiratory Position Using Deformable Image Registration.
AB - PURPOSE: Deformable image registration (DIR) allows modeling of liver tumors on
respiratory correlated (4D) imaging. The mid-position CT was reconstructed for
liver SBRT plans using DIR, and the potential for dose-escalation was
investigated. METHODS: Thirty patients were planned clinically with IMRT for 27
48 Gy in 6 fractions on static exhale 4DCT with PTVs encompassing the breathing
amplitude. For research, exhale 4DCT was deformed to the inhale 4DCT using
biomechanical DIR. The mid-position CT was created by applying a percentage (the
time-averaged normalized position between exhale and inhale calculated from daily
4D cone-beam CT) to this deformation map, assuming a linear trajectory. A
probability-based PTV margin, using patient-specific breathing amplitude from DIR
of 4DCT, was created around the GTV on the mid-position CT where IMRT was re
optimized. Dose was maximally escalated according to clinical protocol (e.g.
liver NTCP <5%). The 4D predicted breathing dose was accumulated by interpolating
the elements' positions at exhale, mid-position and inhale onto the respective
dose matrices (weighted by time spent nearest each matrix) then summed. RESULTS:
Compared the exhale plans, the GTV-to-PTV volume decreased on the mid-position
plans by a mean of 31% (p<0.01, range: 24-38%). Static re-planning on the mid
position CT decreased the mean effective liver volume by 7% (p=0.032), enabling
escalation of the nominal prescribed dose in 80% of patients of 6-12 Gy.
Reconstruction of the 4D predicted breathing dose resulted in a mean increase of
6.7 Gy (p<0.01, maximum increase of 15.0 Gy) in mean GTV dose for the mid
position versus the exhale plan. For the mid-position plan, the minimum 0.5 cm3
GTV dose received 100% of the prescription in the 4D distribution. CONCLUSIONS:
Liver SBRT Planning at the mean respiratory position enables PTV reduction and a
mean dose escalation of 6.7 Gy, potentially improving local control. Dr. Brock
has financial interest in deformable registration technology through the
licensing of Morfeus to RaySearch Laboratories. Research is funded by NIH
1R01CA124714.
PMID- 28517524
TI - SU-E-T-631: Beam Geometry Selection Using Sequential Beam Addition.
AB - PURPOSE: To investigate a beam geometry selection algorithm based on sequential
addition of beams. METHODS: The sequential beam addition algorithm (SBA) requires
an objective function (score) and a set of candidate beam geometries (pool). The
optimal score is determined for each beam in the pool and the best beam selected.
Scores are then calculated for the selected beam in combination with each member
of the pool. The pair with the best score is selected and the score again
determined in combination with each beam in the pool. The process is repeated
until the desired number of beams is reached. We selected 3 treatment sites,
breast, lung, and brain, and determined beam arrangements for up to 11 beams from
a pool comprised of 25 equi-angular transverse beams. For the brain, arrangements
were additionally selected from a pool of 22 non-coplanar beams. Scores were
determined for geometries comprised of equi-angular transverse beams (EQA), as
well as two tangential beams for the breast case. RESULTS: In all cases, SBA
resulted in scores superior to EQA. The breast case had the strongest dependence
on beam geometry, for which only 7 beam EQA had a score better than the
tangential beams, whereas all SBA geometries with more than two beams were
superior. For the lung case, for both EQA and SBA the scores monotonically
improved with increasing number of beams; however, SBA required fewer beams to
achieve scores equivalent to EQA. For the brain case, SBA with a coplanar pool
was equivalent to EQA, while the non-coplanar pool resulted in slightly better
scores; however, the dose-volume histograms demonstrated that the differences
were not clinically significant. CONCLUSIONS: For situations in which beam
geometry has a significant effect on the objective function, SBA can identify
arrangements equivalent to equi-angular geometries but using fewer beams. Varian
Medical Systems.
PMID- 28517525
TI - MO-A-213AB-08: 2D Water Equivalent Path Length Imaging Technique for Pre
Treatment Range Verification in Proton Therapy.
AB - PURPOSE: To assess the potentials of a novel detector for providing a
transmission image of the patient in terms of the Water Equivalent Path Length
(WEPL) values and to evaluate the detector potential for real-time imaging of
moving targets. METHODS: The method is based on the principle that for passively
scattered proton beams the WEPL of any point located in the dose plateau of a
spread-out Bragg-Peak can be derived from the time dependence of the dose rate
function measured at this point. A flat-panel 2D detector array (Sun Nuclear
Corporation, 249 diodes, pitch ~6 mm, 2 ms time resolution) was placed distal to
a range of phantoms with varying complexities. The dose rate received by all
diodes were measured as functions of time and analyzed to obtain the WEPL values.
To assess the potential real-time features of this imaging technique, a Lucite
cube was imaged while moving with a sinusoidal pattern with the amplitude and
period comparable to a typical mobile tumor. RESULTS: In water tanks, millimeter
accuracy in the determination of the WEPL could be achieved and the geometrical
shape of wedge and sphere phantoms could be reproduced. In more complex phantoms
such as a Lucite step-like compensator or Medulloblastoma patient compensators,
multiple Coulomb scattering and range mixing cause a slight deterioration in the
reconstruction of the WEPL. We found that tracking of a moving target in the
coronal plane is potentially feasible. CONCLUSIONS: The technique gives less than
1 cGy of dose to patients and is therefore ideal for 'range-tuning' prior to
treatment. For clinical applications, the beam for 'tuning' will need a deeper
range than the prescription and once the radiological path length to the
dosimeter is determined and compared with that from planning, the proton range
for the actual treatment can be adjusted.
PMID- 28517526
TI - SU-E-T-642: Patient Stratification Based on Improvements in Conformity Indices
and Normal Tissue Sparing with IMRT in Arteriovenous Malformation Treatments.
AB - PURPOSE: Stereotactic radiosurgery (SRS) is a treatment of choice for
Arteriovenous Malformations (AVMs) in anatomical locations associated with a risk
of surgical complication. The aim of this study was: 1) to determine which AVM
patients benefit from IMRT treatment over 3D-Conformal Treatment (3DCRT) based on
PTV size, shape and normal tissue (NT) dose constraints imposed upon IMRT plans;
2) to assess optimized dose distributions against prospectively collected data
for symptomatic radiation injury following SRS. METHODS: 31 patients previously
treated for AVMs with 3DCRT were replanned with static gantry IMRT. PTV volumes,
defined as AVM+1mm margin, ranged from <1cc to >25cc. IMRT plans were generated
for BrainLab microMLC using the iPlan treatment planning system. First, PTV
constraints were used. The conformity of the dose prescribed to the PTV margin
was compared between the two plan types for all patients. Second, NT constraints
were introduced into each IMRT plan at 7Gy and 12Gy. Finally, these dose
constraints were manipulated to achieve maximum NT sparing while maintaining the
desired dose coverage of the PTV. RESULTS: Examination of the conformity index
for an increase of >0.03 showed a separation of patients into those who did and
did not benefit from IMRT. Some patients who did not have a significant benefit
from conformity alone showed a reduction in max PTV dose by as much as 9%.
Moreover, with NT dose constraints, the volume of NT irradiated decreased by a
considerable amount for a subset of patients by 10-21.8% and 9-16.9% for the 7Gy
and 12Gy constraints, respectively. CONCLUSIONS: This work indicates the
potential for significant dose reduction to NT surrounding AVMs and provides
rules to determine which patients are likely to benefit from IMRT. By utilizing
IMRT plans, with and without dose constraints, NT sparing can be improved and
risk of symptomatic injury reduced.
PMID- 28517527
TI - SU-F-BRCD-04: Efficient Scatter Distribution Estimation and Correction in CBCT
Using Concurrent Monte Carlo Fitting.
AB - PURPOSE: X-ray scatter is a known source of image artifacts, contrast reduction,
and CT number inaccuracy in cone-beam CT (CBCT). We present and demonstrate the
performance of a novel scatter correction method based on an algorithm that
simultaneously combines multiple Monte Carlo (MC) CBCT scatter simulations
through the use of a fitting function. METHODS AND MATERIALS: The scatter
estimation system consists of concurrently run MC CBCT scatter projection
simulations that are a sub-sample of the projection angles used in the
reconstruction projection set, P, to be corrected. The photons generated by each
MC simulation are simultaneously aggregated in an algorithm which computes the
scatter detector response, S(i,j,k), for each down-sampled projection location
(i,j) and angle (k). S(i,j,k) is fit to a function, FS, and if FS is determined
to have a specified goodness of fit value the simulations are terminated. FS is
subtracted from P which is subsequently used to create a scatter corrected
reconstruction. The scatter correction method was applied to simulated phantoms
using a frequency limited sum of sines and cosines as the fitting function. Image
quality in the corrected reconstruction was evaluated using metrics looking at
contrast, noise, and artifact reduction. RESULTS: Fitting the scatter
distribution to a limited sum of sine and cosine functions, using a low-pass
filtered Fast Fourier transform, provides a computationally efficient and
accurate fit. Scatter distribution estimates for a 360 image projection set were
computed in under one minute. The scatter correction algorithm increased the
contrast-to-noise ratio by 46%, reduced the shading artifact by 87%, and
decreased the skin line artifact by 79% in reconstructions of a simulated pelvis
phantom. CONCLUSION: The algorithm provides an efficient method for estimating
and removing the scatter distribution in from CBCT projection images. The results
on simulated data show a significant increase in image quality.
PMID- 28517528
TI - SU-E-T-623: Utilizing a Hybrid Optimizer to Improve Dose Conformity during IMRT
Planning.
AB - PURPOSE: For IMRT treatment planning, an index-dose based algorithm features a
fast approach in optimizing beam shapes and weights, and the quasi-Newton method
is adopted in segment weight optimization by many commercial products. By
combining these two optimizers, we aim to improve IMRT plan quality by achieving
better normal tissue sparing. METHODS: An IMRT plan was generated using an in
house treatment planning system in three steps: 1) optimize fluence using beamlet
intensity modulation, 2) generate Multi-collimator leaf sequence and segment
weights, 3) tune the segment shapes and weights as each segment treated as a
single beam. A quick converge was achieved by the optimizer implementing the
index-dose concept in step (1 and 3). To further improve the plan's quality, we
optimized the segment weights via a quasi-Newton gradient search method where a
convex objective function was constructed using both existing segment shapes and
dose constraints defined by the planner. Thus, the segment shapes were optimized
with index-dose, the shapes optimized with quasi-Newton, alternately. The new
approach was evaluated with patient cases including prostate and head & neck.
RESULTS: Both plans had equivalent tumor dose coverage. For the prostate case,
the rectal dose was reduced by 6% for V60% and 2% for V10cc, respectively. For
the head and neck, better sparing was observed for the spinal cord, the left
parotid, and the larynx. CONCLUSIONS: Combining index-dose and quasi- newton
gradient search can effectively improve sparing of normal tissues without
sacrificing target dose coverage. This work indicates the potential of improving
treatment plan quality by integrating different optimization methods.
PMID- 28517529
TI - MO-A-213AB-01: Potential for Focused Low Energy X-Ray Beam for Therapy.
AB - PURPOSE: Megavoltage photon beams are typically used for therapy because of their
skin sparing effect. However, a focused low-energy x-ray beam would also be skin
sparing, and would have a higher dose concentration at the focal spot. Such a
beam can be produced with polycapillary optics. MCNP5 was used to model dose
profiles for a scanned focused beam, using measured beam parameters. The
potential of low energy focused x-ray beams for radiation therapy was assessed.
METHODS: A polycapillary optic was used to focus the x-ray beam from a tungsten
source. The optic was characterized and measurements were performed at 50 KV.
PMMA blocks of varying thicknesses were placed between optic and the focal spot
to observe any variation in the focusing of the beam after passing through the
tissue-equivalent material. The measured energy spectrum was used to model the
focused beam in MCNP5. A source card (SDEF) in MCNP5 was used to simulate the
converging x-ray beam. Dose calculations were performed inside a breast tissue
phantom. RESULTS: The measured focal spot size for the polycapillary optic was
0.2 mm with a depth of field of 5 mm. Focusing was found to remain unchanged
through 40 mm of phantom thickness. The calculated depth dose curve inside the
breast tissue showed a dose peak several centimeters below the skin with a sharp
dose fall off around the focus. The percent dose falls below 10% within 5 mm of
the focus. Rotating the optic during scanning preserves the skin-sparing effect
of the focused beam. CONCLUSIONS: Low energy focused x-ray beams could be used to
irradiate tumors inside soft tissue within 5 cm of the surface.
PMID- 28517530
TI - SU-E-T-635: Effect of Planning Parameters on Tomotherapy Dosimetric Quality and
Treatment Efficiency.
AB - PURPOSE: To investigate how the setting of optimization parameters, fractional
dose and tuning structure in tomotherapy treatment planning affects plan
dosimetric quality and treatment efficiency. METHODS: A digital phantom to
simulate head and neck radiotherapy was constructed for this study. Tumor was
10cm long C-shaped with two surrounding parallel normal structures (P-NS) and one
serial normal structure (S-NS). Dose prescription was 54 Gy in total. Fourteen
treatment plans were generated with varied parameters in five categories: a) jaw
size (1 to 5cm), b) pitch (0.215 to 0.43), c) modulation factor (1.5 to 4), d)
dose per fraction (100 to 600cGy) and e) whether to use tuning structure. Plans
were compared with multiple dosimetric endpoints including target
minimum/maximum/mean dose, V100%, conformity, heterogeneity, S-NS maximum dose, P
NS and body mean dose, and treatment times. The reference plan was defined for
the plan with conventional parameters: jaw 2.5cm, pitch 0.287, modulation factor
3.0, 200cGy per fraction and use of a 2cm ring structure in optimization.
RESULTS: Compared with 2.5cm jaw reference plan, 1cm jaw plan decreased the mean
body dose 10.7% while 5 cm jaw plan increased the dose 17.9%. Smaller pitch
(p=0.215) made the plan more conform than reference plan, and bigger pitch
(p=0.43) had opposite effect. A small modulation factor (M=1.5) failed to spare
critical structures. A medium modulation factor (M=2) resulted in similar plan to
the reference but with 29% less treatment time. A low fractional dose (100 cGy)
planned with similar parameter as reference had much inferior target coverage
(V100%=85.6% vs V100%=96.4). Lastly, the use of tuning structure improved the
conformity of target. CONCLUSIONS: Selection of optimization parameters in
tomotherapy treatment planning affects target coverage, critical structure
sparing, body dose, and treatment time. Target coverage is compromised if
fractional dose is low to the range of 100 cGy.
PMID- 28517531
TI - MO-A-BRB-01: Non-Coplanar Rotational Therapy by Using High Efficient Unflattened
Beams.
AB - : The rapid dose fall-off from treatment target to the adjacent critical organs
has been the Holy Grail for radiotherapy treatment planning. The modern treatment
delivery technologies to address such goal include volumetric modulated
rotational therapy, non-coplanar EVIRT beams and the use of unflattened beams to
reduce the penumbra area. In this lecture, the integration of above techniques
will be presented to achieve the goal of a sharp gradient dose around the target
and also the discussion of middle to low dose volumes. Use of volumetric
modulated rotational therapy by multiple non-coplanar arcs is an idea treatment
modality to focus the high dose in the target area while spreading the low dose
to even larger volume to reduce the middle range dose to surrounding critical
organs. This is especially important for SBRT treatment plans since the fraction
dose is much higher than the traditional fraction schema. The challenges we face
today are 1. the gantry-couch (patient) collision issue for non-coplanar beam
angles, 2. the treatment delivery efficiency due to multiple arc rotations and 3.
the massive inverse optimization computation for multiple rotational arcs can be
resource intensive and time consuming for treatment plan systems. It might not be
easy to resolve all the challenges at one time. However, the high efficient
unflattened beam can certainly improve the delivery speed by reducing the beam-
on time and this, again, is essential to SBRT patients with high fractional dose.
In this lecture, the non-coplanar rotational therapy treatment planning
techniques will be presented and be evaluated by using comformality index,
gradient index as well as dose volume histogram comparison. The differences in
treatment delivery time will be tabulated and compared. At the end, the high
medium-low dose volumes will be illustrated with radiobiological models for the
philosophy of sun tanned versus sun burned. LEARNING OBJECTIVES: 1. Understand
treatment plan and dose gradient advantages of using non- coplanar rotational
therapy 2. Understand potential delivery efficiency by using unflattened beams
for multiple non-coplanar rotational beams 3. Understand sun tanned versus sun
burned: the low dose volume and integrated dose.
PMID- 28517533
TI - SU-F-BRCD-08: Uncertainty Quantification by Generalized Polynomial Chaos for MR
Guided Laser Induced Thermal Therapy.
AB - PURPOSE: Magnetic resonance-guided laser induced thermal therapy (MRgLITT) is a
minimally invasive thermal treatment for metastatic brain lesions, offering an
alternative to conventional surgery. The purpose of this investigation is to
incorporate uncertainty quantification (UQ) into the biothermal parameters used
in the Pennes bioheat transfer equation (BHT), in order to account for imprecise
values available in the literature. The BHT is a partial differential equation
commonly used in thermal therapy models. METHODS: MRgLITT was performed on an in
vivo canine brain in a previous investigation. The canine MRgLITT was modeled
using the BHT. The BHT has four parameters'" microperfusion, conductivity,
optical absorption, and optical scattering'"which lack precise measurements in
living brain and tumor. The uncertainties in the parameters were expressed as
probability distribution functions derived from literature values. A univariate
generalized polynomial chaos (gPC) expansion was applied to the stochastic BHT.
The gPC approach to UQ provides a novel methodology to calculate spatio-temporal
voxel-wise means and variances of the predicted temperature distributions. The
performance of the gPC predictions were evaluated retrospectively by comparison
with MR thermal imaging (MRTI) acquired during the MRgLITT procedure in the
canine model. The comparison was evaluated with root mean square difference
(RMSD), isotherm contours, spatial profiles, and z-tests. RESULTS: The peak RMSD
was ~1.5 standard deviations for microperfusion, conductivity, and optical
absorption, while optical scattering was ~2.2 standard deviations. Isotherm
contours and spatial profiles of the simulation's predicted mean plus or minus
two standard deviations demonstrate the MRTI temperature was enclosed by the
model's isotherm confidence interval predictions. An a = 0.01 z-test demonstrates
agreement. CONCLUSIONS: The application of gPC for UQ is a potentially powerful
means for providing predictive simulations despite poorly known input parameters.
gPC provides an output that represents the probable distribution of outcomes for
MRgLITT.
PMID- 28517532
TI - SU-E-T-646: Feasibility Study of Proton Arc Therapy for the Treatment of Para
Aortic Lymph Node Tumor.
AB - PURPOSE: To test feasibility of proton arc therapy (PAT) in the treatment of para
aortic lymph node tumor and compare its dosimetric properties with advanced
radiotherapy techniques such as intensity modulated radiation therapy (IMRT) and
conventional 3D conformal proton beam therapy (PBT). METHODS: The treatment plans
for para-aortic lymph node tumor were planned for 9 patients treated at our
institution using IMRT, PBT, and PAT. Feasibility test and dosimetric evaluation
were based on comparisons of dose volume histograms (DVHs) which reveal mean
dose, D30%, D60%, D90%, V30%, V60%, V90%, organ equivalent doses (OEDs), normal
tissue complication probability (NTCP), homogeneity index (HI) and conformity
index (CI). RESULTS: The average doses delivered by PAT to the liver, kidney,
small bowel, duodenum, stomach were 7.6%, 3%, 17.3%, 26.7%, and 14.4%, of the
prescription dose (PD), respectively, which is higher than the doses delivered by
IMRT (0.4%, 7.2%, 14.2%, 15.9%, and 12.8%, respectively) and PBT (4.9%, 0.5%,
14.12%, 16.1% 9.9%, respectively). The average homogeneity index and conformity
index of tumor using PAT were 12.1 and 1.21, respectively which were much better
than IMRT (21.5 and 1.47, respectively) and comparable to PBT (13.1 and 1.23,
respectively). The Result shows that both NTCP and OED of PAT are generally lower
than IMRT and PBT. CONCLUSIONS: This study demonstrates that PAT is better in
target conformity and homogeneity than IMRT and PBT but worse than IMRT and PBT
for most of dosimetric factor which indicate that PAT is not recommended for the
treatment of para-aortic lymph node tumor.
PMID- 28517534
TI - SU-E-T-627: Optimal Partial Arcs in VMAT Planning.
AB - PURPOSE: To describe a method for producing minimal delivery time partial arc
VMAT plans. METHODS: We begin with the assumption that dose quality is the
primary treatment planning goal. Therefore the first step in the partial arc
computation is a 180 beam equi-spaced IMRT multi-criteria optimized treatment
plan, which serves as an ideal plan, along with a set of user- specified
allowable deviations from this plan. This defines a set of target coverage and
healthy organ sparing constraints. We then seek a partial arc plan which recovers
this ideal plan but is minimal in delivery time. The search for the optimal
partial arc which fulfills the hard constraints is done by wrapping a VMAT
fluence map optimization/merging/simplification algorithm called VMERGE. The
search is performed over all possible partial arcs, with start and end locations
discretized to 20 degree increments, and respecting that the gantry cannot pass
underneath the couch. This results in 169 partial arcs. For the ones that yield
feasible plans, the complete VMERGE algorithm is run, which minimizes the
delivery time for that arc. The minimal delivery time plan that fulfills the
dosimetric requirements is returned. RESULTS: We apply the method to a lung and
liver case. The time savings are as follows: (full arc time, optimal partial arc
time): lung (185 s, 94 s), liver (263 s, 165 s). The optimal arc for the lung
lesion, a left anterior target, is 140 degrees centered at 50 degrees. The
optimal arc for the liver lesion is 160 degrees centered at -90 degrees.
CONCLUSIONS: By wrapping a fast VMAT optimization/sequencing routine by an
exhaustive search over 169 possible partial arcs, we are able to determine the
fastest delivery partial arc. The use of partial arcs can significantly shorten
delivery time in VMAT delivery. The project described was supported by Award
Number R01CA103904 from the National Cancer Institute. The content is solely the
responsibility of the authors and does not necessarily represent the ocial views
of the National Cancer Institute or the National Institutes of Health.
PMID- 28517535
TI - MO-A-213AB-05: Synthesis of High Quantum Yield Nano-Scintillators for
Simultaneous Photodynamic Therapy in Radiotherapy.
AB - PURPOSE: Radioresistant tumors provide one of the biggest challenges for
improving radiation therapy efficacy. We have demonstrated that semiconductor
quantum dots can be used as 'impedance matching' devices converting high energy X
rays to visible photon range for a simultaneous and mechanistically independent
treatment; photodynamic therapy (PDT). Application of quantum dots was limited by
it toxicity and relatively low quantum yield with X-ray excitation. To further
improve the combined therapy strategy, we synthesize and screen for safer and
more efficient nanoparticles. METHODS: Colloidal GdSe and Gd2O3 nanoparticles
were synthesized in octadecene using octylamine and oleic acid as surfactants.
The average diameter of the nanoparticles was 10 nm. The samples in organic
solution was secured in a light tight box and irradiated by 300 kVp X-rays with a
dose rate of 300 cGy/min. The visible photon yield is collected by a lens and
transferred to the photomultiplier tube via optic fibers. The average photon
counts for 100 seconds were compared between GdSe, Gd2O3 and CdSe quantum dots.
RESULTS: Different than quantum dots with fixed band gap and emission peaks, the
fluorescent peaks of GdSe and Gd2O3 were excitation light dependent. Shorter
emission wavelengths were resulted from higher incident photon energies but the
spectra overlap well with the Soret band of porphyrin photosensitizers. While
their fluorescence is substantially weaker compared with QDs under UV excitation,
fluorescence from both GdSe and Gd2O3 is one order of magnitude stronger than
that of QD when excited by 300 kV X-rays. CONCLUSIONS: Metal oxide nanoparticle
scintillators are more efficient X-ray scintillators than Quantum dots. Moreover,
Metal oxide nanoparticle can utilize the Soret band of photosensitizers for more
effective energy transfer and excitation. These improvements will reduce the
required radiation dose and drug concentration for simultaneous photodynamic
therapy.
PMID- 28517536
TI - SU-E-T-639: Dosimetric Evaluation of VMAT for the Treatment of NSCLC with SBRT.
AB - PURPOSE: To demonstrate the dosimetric potential of volumetric modulated arc
therapy (VMAT) for the treatment of patients with medically inoperable stage I/II
non-small cell lung cancer (NSCLC) with stereotactic body radiation therapy
(SBRT). METHODS: Fourteen patients treated with 3D-CRT with varying tumor
locations, tumor sizes and dose fractionation schemes were chosen for study. The
target prescription doses were 48 Gy in 4 fractions, 52.5 Gy in 5 fractions, 57.5
Gy in 5 fractions and 60 Gy in 3 fractions for 2, 5, 1 and 6 patients,
respectively. VMAT treatment plans with a mix of 2-3 full and/or partial non
coplanar arcs with 5 degrees -25 degrees separations were retrospectively
generated using Eclipse version 10.0. The 3D-CRT and VMAT plans were then
evaluated by comparing their target dose, critical structure dose, high dose
spillage, and low dose spillage as defined according to RTOG 0813 and RTOG 0236
protocols. RESULTS: The VMAT treatment plans yielded an average 9.6-33.7%
reduction in dose to critical structures and an average 12.0-12.5% increase in
conformity compared with the treated 3D-CRT plans. The D2cm improved with VMAT in
11 of 14 cases. The 3 that worsened were still within the acceptance criteria. Of
the 14 3D-CRT plans, 7 had a D2cm minor deviation, while only one of the 14 VMAT
plans had a D2cm minor deviation. The R50% improved in 13 of the 14 VMAT cases.
The 1 case that worsened was still within the acceptance criteria of the RTOG
protocol. Of the 14 3D-CRT plans, 7 had an R50% deviation. Only 1 of the 14 VMAT
plans had an R50% deviation, but it was still improved compared to the 3D-CRT
plan. CONCLUSIONS: In this cohort of patients, no dosimetric compromises resulted
from planning SBRT treatments with VMAT relative to the 3D-CRT treatment plans
actually used in their treatment.
PMID- 28517537
TI - SU-F-BRCD-01: A Novel Dual Source Array Tetrahedron Beam Computed Tomography
(TBCT) System for Image Guided Radiotherapy.
AB - PURPOSE: To design and test the feasibility of a novel dual source array, dual
detector array TBCT system which is capable of both volumetric CT imaging as well
as real-time stereoscopic x-ray imaging for image guided radiotherapy (IGRT).
METHODS: Besides producing improved image quality, the geometry of TBCT is also
more compact and flexible. It is possible to mount two x-ray source arrays and
two detector arrays on a LINAC gantry. Each pair of source/detector arrays
generates real-time fluoroscopy images at four different view angles, which can
be used in real-time target/marker tracking. FDK and iterative CT image
reconstruction algorithms were developed for this new geometry. Stereoscopic
imaging was simulated using CT images of prostate patients with implanted
radiopaque markers. RESULTS: Although the cone angles to the central slice of the
reconstructed image are nonzero due to the shifting of the detector arrays,
reconstructed patient CT images are visually identical to the original fan beam
images. Anatomical structures and implanted radiopaque markers are visible in at
least two of the radiography images. The 3-D spatial coordinates of the implanted
markers can be determined from the stereoscopic images. CONCLUSIONS: TBCT with
dual source and dual detector arrays can produce high quality CT images as well
as real-time stereoscopic imaging for target tracking. High quality online CT
images and stereoscopic imaging in MV beam-eye-view direction can be very useful
for advanced treatment techniques. Tiezhi Zhang and Joshua Kim have financial
interest in TetraImaging Inc.
PMID- 28517538
TI - SU-E-T-641: Flattening Filter Free Dynamic Conformal Arcs for Lung Radiotherapy.
AB - PURPOSE: To investigate the use of dynamic conformal arcs (DCA) with the
flattening filter free (FFF) beams for lung stereotactic body radiotherapy (SBRT)
on the TrueBeam STx (Varian, Inc., Palo Alto, CA). METHODS: Eight SBRT patients
receiving 10-18 Gy per fraction were planned in Eclipse 10 (Varian Medical
Systems, Palo Alto, CA) for the TrueBeam STx using DCA's with 6 MV FFF beams. The
isocenter was placed such that the point fell near midline on each patient
allowing full arc rotation without patient collision.Several planning methods
were employed depending on the location of the tumor. For peripheral tumors a
single arc was used. For peripheral tumors with chestwall interference,
additional oblique fields were used to help pull dose off of the chestwall. For
tumors located in the central region or close to the spine, multiple DCA's were
used. One standard open DCA was used to deliver the majority of the dose, then
one or two additional DCA's with organs blocked automatically using the'Fit and
Shield' feature of Eclipse were used to help shape the dose. The arcs were then
weighted to create the desired dose distribution. RESULTS: Beam on times for the
8 patients averaged 2.00 minutes with a minimum time of 1.22 minutes and a
maximum time of 3.3 minutes total. With multiple arcs or additional static
fields, treatment time is lengthened by the time it takes to mode up between arcs
(~1 minute) and/or move between fields. The PTV coverage of the 100% isodose line
was >= 95% in all cases. The conformality index ranged 1.12 - 4.5, with an
average of 2.5. CONCLUSIONS: FFF DCA is a fast, efficient way to plan and
delivery SBRT treatments. The short treatment times directly lead to reduced
patient motion and discomfort, which may yield improved targeting and outcomes.
PMID- 28517539
TI - SU-F-BRCD-03: Dose Calculation of Electron Therapy Using Improved Lateral Buildup
Ratio Method.
AB - PURPOSE: To calculate the percentage depth dose of any irregular shape electron
beam using modified lateral build-up-ratio method. METHOD AND MATERIALS:
Percentage depth dose (PDD) curves were measured using 6, 9, 12, and 15MeV
electron beam energies for applicator cone sizes of 6*6, 10*10, 14*14, and
14*14cm2 . Circular cutouts for each cone were prepared from 2.0cm diameter to
the maximum possible size for each cone. In addition, three irregular cutouts
were prepared. The scanning was done using a water tank and two diodes - one for
the signal and the other a stationary reference outside the tank. The water
surface was determined by scanning the signal diode slowly from water to air and
by noting the sharp change of the percentage depth dose curve at the water/air
interface. RESULTS: The lateral build-up-ratio (LBR) for each circular cutout was
calculated from the measured PDD curve using the open field of the 14*14 cm2 cone
as the reference field. Using the LBR values and the radius of the circular
cutouts, the corresponding lateral spread parameter (sigma) of the electron
shower was calculated. Unlike the commonly accepted assumption that sigma is
independent of cutout size, it is shown that the sigma value increases linearly
with circular cutout size. Using this characteristic of sigma, the PDD curves of
irregularly shaped cutouts were calculated. Finally, the calculated PDD curves
were compared with measured PDD curves. CONCLUSIONS: In this research, it is
shown that sigma increases with cutout size. For radius of circular cutout sizes
up to the equilibrium range of the electron beam, the increase of sigma with the
cutout size is linear. The percentage difference of the calculated PDD from the
measured PDD for irregularly shaped cutouts was under 1.0%. Similar Result was
obtained for four electron beam energies (6, 9, 12, and 15MeV).
PMID- 28517540
TI - SU-E-T-622: A Rapid Hybrid VMAT-IMRT Planning Method Using an Abbreviated Beam
Angle Optimization Search.
AB - PURPOSE: To generate hybrid VMAT-IMRT treatment plans by utilizing an IMRT beam
angle-optimality (BAO) search under a commercially available TPS without the aid
of custom optimization software or high performance computing. METHODS: The high
dose modulation provided by IMRT beams can be exploited to improve the quality of
VMAT treatments. To achieve this, a VMAT treatment was created where the gantry
pauses at predetermined angles to deliver IMRT segments. To determine IMRT BAO,
an IMRT plan ('poly-IMRT') was made with many beams (>30) equally spaced around
the patient. For practical reasons and to reduce the total time to approximately
1 hour, BAO was approximated by removing one beam out of the set and noting the
new objective score. Determining this'score penalty' for each of the beams serves
as a proxy for true BAO. The hybrid plan was created by combining the VMAT arc
with a user-determined number of top-ranked beams from the poly-IMRT set. The BAO
from this approach was compared with a more rigorous method ('VMAT+1'), in which
a VMAT plan was optimized with 1 IMRT beam at various angles, allowing a direct
determination of objective score versus gantry angle. The overall hybrid planning
process was demonstrated by creating separate plans for a SBRT lung patient, with
dose normalized to the limiting maximum aorta dose. RESULTS: Large score
penalties from poly-IMRT coincided with large score benefits from VMAT+1,
indicating both methods identified the same optimal beams. The VMAT, IMRT, and
hybrid plans delivered the prescription dose to 84.3%, 85.6% and 87.7% of the PTV
and had homogeneity indices of 1.38, 1.41, and 1.32 respectively. Normal tissue
doses were within 0.5%. CONCLUSION: The presented method can create hybrid VMAT
IMRT plans which combine delivery efficiency with improved target coverage. The
planning process takes about an hour using a standard TPS.
PMID- 28517541
TI - MO-A-211-01: Volumetric Modulated Arc Therapy.
AB - : Volumetric Modulated Arc Therapy (VMAT) is a rotational approach to the
delivery of intensity modulated radiation therapy (IMRT) that can be delivered on
a conventional linear accelerator. VMAT combines the dosimetric advantages of
rotational delivery with the dose painting capabilities of IMRT. In recent years,
VMAT has become a widely adopted clinical tool due to the conformal nature of the
dose distributions and the efficiency of VMAT delivery. In this session, we will
provide an overview of the VMAT delivery technique and will describe recommended
steps for starting a VMAT program including VMAT commissioning. We will discuss
tips and tricks for the use of VMAT for key clinical sites such as head-and-neck
and prostate. Additionally, we will detail the role of VMAT for stereotactic
radiosurgery (SRS) and stereotactic body radiation therapy (SBRT). More advanced
VMAT topics will also be discussed such as flattening filter free VMAT, gated
VMAT, and the use of couch rotations during VMAT delivery. LEARNING OBJECTIVES:
1. Describe volumetric modulated arc therapy (VMAT). 2. Describe commissioning of
a VMAT delivery system. 3. Summarize the key elements of starting a VMAT program.
4. Review patient- and machine-specific VMAT quality assurance. 5. Survey VMAT
treatment planning systems and planning techniques. 6. Describe advanced VMAT
techniques such as gated VMAT and flattening filter free VMAT. CONFLICT OF
INTEREST: Richard Popple has a sponsored research agreement with Varian. David
Shepard has a sponsored research agreement with Elekta.
PMID- 28517542
TI - SU-E-T-634: Convex Direct Aperture Optimization for Sliding Window IMRT.
AB - PURPOSE: To introduce a convex Direct Aperture Optimization (DAO) technique for
sliding window IMRT. This method combines the accuracy of aperture-based dose
calculations, which include leaf end effect, scatter, and leakage, with the
convexity, and hence efficient solvability, of classic two phase IMRT
optimization (fluence map optimization followed by sliding window leaf
sequencing). METHODS: Artificial pencil beam profiles used in fluence map
optimization are replaced with sigmoid-like profiles representing the dose
"blocked" by a leaf while at some incremental position, per MU. More precisely,
the profiles represent the dose from photons blocked minus that from photons
leaked through or scattered by the leaf. These profiles can be computed by any
clinically validated IMRT dose engine, and the scatter component for an
individual leaf can be accurately included to the extent that it is independent
of positions of other leaves. Variables of the resulting convex optimization are
the MUs delivered while each leaf is at each incremental position. All
constraints necessary to ensure a deliverable sliding window solution, such as
those preventing leaf collision, are linear. Thus, provided the dose objective
functions are convex, the entire IMRT optimization is convex, and therefore can
be efficiently solved to provable optimality. RESULTS: Our derivations prove that
DAO is convex for sliding window IMRT, and we demonstrate the technique on a
clinical prostate case. CONCLUSIONS: By moving from the standard idealized
fluence beamlet approach to a'fluence blocked by a leaf at position x' approach,
we fully convexify the sliding window IMRT optimization problem, and thus avoid
the dose degradation observed in two-step IMRT optimization and the non-convexity
of the traditionally posed DAO problem.
PMID- 28517544
TI - SU-E-T-645: Treatment of Multiple Brain Metastases Using Stereotactic
Radiosurgery with Single-Isocenter Volumetric Modulated Arc Therapy: Comparison
with Conventional Dynamic Conformal Arc and Static Beam Stereotactic
Radiosurgery.
AB - PURPOSE: To investigate the treatment of multiple brain metastases using
stereotactic radiosurgery with single-isocenter volumetric modulated arc therapy
(VMAT) compared with conventional multi-isocenter dynamic conformal arc therapy
(DCAT) and three-dimensional conformal radiation therapy (3D-CRT). METHODS:
Seventeen patients with 2 to 5 brain metastatic lesions were studied. The number
of patients with 5, 4, 3, and 2 lesions were 4, 5, 4, and 4, respectively. For
patients treated with DCAT/3D-CRT plans, VMAT plans were retrospectively
generated, and vice versa. Single-isocenter set up was employed in VMAT plans
while the number of isocenters was proportional to the number of lesions in
DCAT/3D-CRT plans. The DCAT/3D-CRT and VMAT plans were generated using iPlan(r)
RT Dose Version 4.1.1 (BrainLAB, Germany) and EclipseTM Version 8.6 (Varian, USA)
treatment planning system, respectively. All plans were designed to be delivered
on Novalis TxTM system (Varian, USA and BrainLAB, Germany), in which the
accelerator equipped with a high definition multileaf collimator (HDMLC).
RESULTS: Conformity index for VMAT plans were equivalent to or better than that
for DCAT/3D-CRT plans. While VMAT and DCAT/3D-CRT plans were similar in target
coverage, quality of coverage for VMAT plans was better. However, the volume
receiving 5Gy was 46% larger for VMAT plans. In addition, the distance from
individual lesion to the VMAT isocenter has no impact on VMAT plans. Compared
with DCAT/3D-CRT plans, the mean monitor units (MU) decreased by 42% and the
estimated treatment time decreased by 49% for VMAT plans. CONCLUSIONS: This work
suggests that single-isocenter VMAT is promising for stereotactic radiosurgery in
the treatment of multiple brain metastases. Single-isocenter VMAT is able to
achieve comparable conformity, target coverage and quality of coverage with
significantly superior delivery efficiency.
PMID- 28517545
TI - SU-F-BRCD-07: Experimental Validation of Fluence Field Modulation for Noise and
Dose Management in CT.
AB - PURPOSE: Dose management in CT is a growing concern as the number of CT scans per
capita rises. Fluence field modulated computed tomography (FFMCT) is a proposed
approach for more optimal dose management, where the incident fluence pattern can
change independently for each projection in order to minimize dose while meeting
prescribed image quality metrics. This work studies the application of FFMCT for
dose and noise management to a small cylindrical phantom. METHODS: Experiments
were carried out on an experimental CT system using a small cylindrical phantom
comprised of acrylic spheres, water and teflon rods as the object of interest.
Modulation of the incident fluence was optimized using a simulated annealing
algorithm that attempts to achieve user-prescribed, regionally varying SNR
criteria while limiting dose. The modulated projections were synthesized from
projection sets taken at various tube current settings. SNR patterns and
predicted dose outcomes were compared to the prescribed values as well as against
expected results using a bowtie filter. RESULTS: FFMCT resulted in SNR outcomes
with greater agreement to the prescribed regionally varying SNR criteria than
achieved by the bowtie filter. Dose reductions were observed for the majority of
the object, and reached as high as 60%. Limited regions, coinciding with lower
noise, observed dose increases less than 20%. Integral dose reduction over the
entire object was greater than 40% when compared to a bowtie filter with
comparable image quality in the region of interest. CONCLUSIONS: The results
support the hypothesis that FFMCT has the potential to meet user-prescribed,
regionally varying image quality objectives, while decreasing radiation dose to
the patient. These results suggest that given a suitable collimator approach,
fluence field modulated computed tomography could reap significant benefits in
terms of reducing dose and optimizing image quality. NSERC.
PMID- 28517546
TI - SU-E-T-626: Individualized Trade-Off of Dose Coverage and Sparing in IMRT
Planning.
AB - PURPOSE: We present an evidence-based approach to quantifying the dose sparing
trade-offs between different Organs-at-risk (OARs) and the trade-off between OAR
dose sparing and target dose coverage in IMRT plans. METHODS: The interaction
between dose sparing of different OARs and between target dose coverage and OAR
dose sparing are modeled using high-quality prior IMRT plans of prostate, head
and-neck (HN), and spine SBRT cases. The dose sparing for each OAR is modeled
separately at first based on their own anatomical features and then the
contributions from other OARs or PTV are added into the model to account for the
possible trade-off effects in plans whose modeled OAR DVH deviates from that of
actual plans. RESULTS: The most significant OAR dose sparing trade-off is between
bladder and rectum in prostate plans and between the left and the right parotids
in HN plans. Trade-off is most apparent when the parotid on one side has very
large overlap with the PTV. In most of these plans (83%), the planer chooses to
loosen the dose constraint for that parotid in exchange for lower contra-lateral
parotid median dose. The interaction between OAR dose sparing and PTV dose
coverage is most significant in spine SBRT plans, (R2=0.37). Another important
factor is the tightness of the geometric enclosure of PTV around OAR (R2=0.38).
CONCLUSIONS: The dosimetric trade-off between multiple OARs and between PTV and
OAR in IMRT planning is quantified by studying prior plans. These findings will
help physicians and planners obtain better OAR dose sparing by exploring
different trade-off options for individual patient cases. Partially supported by
a master research agreement with Varian Medical Systems, Inc.
PMID- 28517543
TI - MO-A-213AB-11: First Experimental Test of Secondary Ion Tracking for the
Assessment of Beam Range in a Patient-Like Phantom.
AB - PURPOSE: Radiation therapy with ion beams provides highly conformal dose
distributions. Therefore, monitoring the dose delivery within the patient in a
non- invasive way is desired. The clinically available method based on tissue
activation measurements with a PET-camera shows limitations due to the low
induced activities and biological washout of the activated nuclei. The prompt
production of secondary ions is supposed to be less influenced by biological
processes. This contribution investigates the feasibility of beam range
monitoring in a patient-like geometry containing realistic tissue
inhomogeneities. METHODS: The experiments were performed at the Heidelberg Ion
Beam Therapy Center in Germany using carbon ion beams of 213 and 250MeV/u. Static
pencil beams (FWHM of 6mm) were applied to the skull base and brain regions of a
head phantom containing real bones. The emerging secondary ions were registered
by the silicon detector Timepix. It was developed by the Medipix Collaboration
and provides 256*256 pixels with 55um pitch. To determine the direction of the
particles, a multi-layered detector (3D voxel detector, J.Jakubek etal. JINST6
C12010) was employed. The contribution of K. Gwosch etal. addresses the
performance of this method in a homogeneous phantom. RESULTS: In the 3D
distributions of the measured secondary ions clear differences between the
application of lower and higher energies were observed. This Result was achieved
in both brain (homogeneous) and skull base regions (containing inhomogeneities).
Differences between the energies could be observed with the detector positioned
on the occipital side as well as on the facial side of the head. CONCLUSIONS: We
performed the first experiments towards beam range monitoring in a patient-like
geometry exploiting tracking of prompt secondary ions with a small detector
prototype. Despite the inherent tissue inhomogeneities, we found sensitivity on
the beam range in both brain and skull base. Research carried out in frame of the
Medipix Collaboration. Research carried out in frame of the Medipix
Collaboration.
PMID- 28517547
TI - MO-A-213AB-04: Verification of 4D Dose Delivery Using 4D Digital Human Phantom.
AB - PURPOSE: At present, techniques of 4D dose verification in radiation therapy for
lung cancers associated with respiratory motion are very limited, due to either
lack of patient anatomy or breathing information. The aim of this study is to
develop a 4D dose verification technique based on XCAT phantom which incorporates
both patient anatomy and respiratory mechanics. MATERIALS AND METHODS: The 4D
XCAT phantom which possesses patient specific anatomy and allows input of
respiratory parameters was generated using an integrated Matlab program. 10-phase
4DCT, MIP, and AIP images generated from 4D-XCAT were used for designing a 3D
conformal treatment plan. Real-time dose delivery was simulated by calculating
the deposited dose in each phase of 4D-XCAT for each beam with fixed individual
planning dose. The 4D delivered dose was determined by accumulating dose
deposition of all beams in all phases using deformable image registration
implemented in VelocityAl software. The planned and delivered doses were compared
based on target coverage and DVHs of OARs (lungs, cord, heart, and esophagus).
RESULTS: Target volume coverage was 97.5% in the simulated real-time delivery, as
compared to 95% as planned based on AIP. Maximum cord dose, maximum esophagus
dose, mean heart dose, and V20Gy of lung were comparable between the planned and
delivered dose; the relative difference were 0.3%, 4.0%, 0%, and 2.8%,
respectively. These results indicates AIP-based planning was a close
representation of the real 4D dose delivery for both target and OARs when the
breathing pattern is regular and reproducible. CONCLUSION: A framework has been
successfully established for verifying 4D dose delivery using the 4D-XCAT phantom
and deformable image registration. This verification method is capable of
incorporating specific patient anatomy and respiratory mechanics.
PMID- 28517548
TI - SU-E-T-638: Treatment Margins Expansion for CyberKnife Treatment Plans.
AB - PURPOSE: The CyberKnife uses an online prediction model to track moving targets.
The system works well if patients can breathe regularly. However, some patients
cannot maintain a regular breathing pattern, which means a larger PTV margin is
necessary for these patients to ensure sufficient CTV dose coverage. However, it
is very difficult to predict a patient's breathing pattern in advance. The
purpose of this study is to investigate a quick and easy way to adapt the
treatment plan if extra margins are needed. METHODS: Multiple algorithms have
been developed to calculate the adjustment. Generally, if a larger target region
requires coverage by the prescription dose, the size of the beams will be larger
and they should move in a peripheral direction for a certain distance to avoid
hot spots. Dose is recalculated and renormalized consistently after the
adjustment. If the dose distribution of the new plan covers the new PTV with
acceptable conformality and coverage, the plan will be used for treatment.
Otherwise, more iterations of the adjustment are performed. Dose calculations are
limited to a small region surrounding the target to reduce calculation time.
RESULTS: 5 clinical cases (3 lungs, 1 liver and 1 adrenal) have been tested in
this study. The dose margin can be extended up to 10 mm without changing dose
distributions around the target region dramatically. The average PTV coverage is
98.7% compared to 99.1% in the original plans and the average CI is 1.22, which
is slightly less than the 1.24 in the original plans. CONCLUSIONS: Treatment
margins can be sufficiently expanded resulting in satisfactory plan quality for
patients with breathing irregularities.
PMID- 28517549
TI - SU-E-T-649: Evaluation of RapidArc- Based Stereotactic Cranial Radiotherapy Plans
with MU Objective Using Multiple Non Coplanar Arcs in Comparison with
Conventional Dynamic Conformal Arc Technique.
AB - PURPOSE: Previous researches reported that RapidArc plans for stereotactic
cranial radiotherapy have two to three times more MUs as compared to Conventional
Dynamic Conformal Arc (DCA) Technique. This study aims to evaluate RapidArc plans
using multiple non- coplanar arcs, developed with MU objective constraint in the
optimization stage. METHODS: Five single brain metastasis and three multiple
metastases cases previously planned using DCA techniques in BrainLab iPlan
Version 4.1 were investigated in this study. For each case, the target was
defined on CT-MR fused images in iPlan. The CT images and contours of these
patients were exported from iPlan to Varian Eclipse TPS Version 8.6. For each
case, a DCA plan and a RapidArc plan with multiple non-coplanar arcs with and
without using MU objective in the optimization stage were generated using Varian
Trilogy machine with Millennium 120 MLC keeping the same prescription and
critical structure dose limits. All plans were evaluated according to Conformity
Index (CI-modified Paddick) Homogeneity Index (HI), and the normal tissue volume
receiving various dose levels (V80%, V50%, V25% and V10%). RESULTS: In all the
plans, the target objectives were met and dose to OARs was within tolerance dose
constraints. RapidArc plans with and without MU objective showed better CI and HI
as supposed to DCA plans. V80%, V50%, V25% and V10% of normal tissue for RapidArc
plans are equal or lesser than DCA plans. Single isocentre RapidArc plan for
closely spaced multiple metastases cases showed better dose fall off between the
lesions as supposed to DCA plans. RapidArc plans with MU objective resulted in
comparable MUs as that of DCA plans. CONCLUSIONS: Our study showed RapidArc plans
done with and without MU objective have no significant dosimetric difference in
plan objectives. Therefore, multiple non-coplanar RapidArc plans with MU
objective is clinically feasible and can provide better treatment plans than
conventional DCA plans, especially for complicated cases.
PMID- 28517550
TI - SU-E-T-619: A Network-Flow Solution Approach to VMAT Treatment Plan Optimization.
AB - PURPOSE: To add mathematical rigor to the merging phase of the recently published
two-stage VMAT optimization method called VMERGE. Using an exact merging method,
we are able to better characterize the tradeoff between delivery efficiency and
dose quality. METHODS: VMERGE begins with an IMRT plan that uses 180 equi-spaced
beams and yields the "ideal" dose. Neighboring fluence maps are successively
merged, meaning they are added together and delivered as one map. The merging
process improves the delivery time at the expense of deviating from the initial
high-quality dose distribution. We replace the original heuristic merging method
by considering the merging problem as a bi-criteria optimization problem:
maximize treatment efficiency and minimize the deviation from the ideal dose. We
formulate this using a network-flow model where nodes represent the beam angles
along with the starting MLC leaf position and arcs represent the possible merges.
Since the problem is non-convex, we employ a customized box algorithm to obtain
the Pareto approximation. We also evaluate the performance of several simple
heuristics. RESULTS: We test our exact and heuristic solution approaches on a
pancreas and a prostate case. For both cases, the shape of the Pareto frontier
suggests that starting from a high quality plan, we can obtain efficient VMAT
plans through merging neighboring arcs without substantially deviating from the
initial dose distribution. The trade-off curves obtained by the various
heuristics are contrasted and shown to all be equally capable of initial plan
simplifications, but to deviate in quality for more drastic efficiency
improvements. CONCLUSIONS: This work presents a bi-criteria network-flow solution
approach to the merging problem. The obtained Pareto-frontier approximation is
used as a benchmark to evaluate the performance of the proposed merging
heuristics. The results validate that one of the heuristics in particular can
achieve high-quality solutions.
PMID- 28517551
TI - MO-A-BRCD-01: Unsettled Issues in the Radiobiology of Emergent Technology:
Hypofractionation and PET-Guided Treatment Planning.
AB - : New technologies and innovative treatment techniques call into question long
standing radiobiological principles in RT. Reported apoptosis effects above 10
Gy/fraction challenge standard views of tumor cell kill as the only important
path to tumor control. There are also reports of an immune-system response to
large-dose per fraction. Repair-kinetics can also become important when comparing
treatments given in less than 10 minutes to treatments given over 30 minutes or
more. Modeling studies challenge the importance of hypoxia (and use of the linear
quadratic model) in hypofractionation treatments. Critical questions regarding
the use of FDG-PET guided boosts include the expected dose needed to achieve
local control for FDG-PET positive tumors, and the relationship between FDG-PET
images and underlying cellular parameters. This symposium will review our current
scientific understanding of these important, unsettled issues. LEARNING
OBJECTIVES: 1. Review non-classical radiobiology relevant to high-doses per
fraction 2. Review dose-rate effects as they apply to SBRT/hypofx treatments 3.
Review radiobiology of FDG-PET guided therapy.
PMID- 28517552
TI - Clinical and radiographic outcomes of immediate and delayed placement of dental
implants in molar and premolar regions.
AB - PURPOSE: The purpose of this retrospective study was to determine clinical and
radiographic outcomes of immediate and delayed placement of dental implants in
molar and premolar regions. MATERIALS AND METHODS: Clinical and radiographic
records of 116 patients who received implants in molar and premolar regions were
included in this study. After implantation, patients were recalled for
assessments at 1 month, 3 months, 6 months, 1 year, and every year thereafter. In
addition, anatomic location, type of prosthesis, gender, stage, diameter, and
length of implants were analyzed. RESULTS: Of these 116 patients, 55 were males,
and 61 were females. Their mean age was 50.9 years. They received 85 immediate
implants and 147 delayed implants in molar and premolar regions. Gender, type of
prosthesis, stage, implant diameter, and implant length were not significantly
different between the immediate placement group and the delayed placement group,
although anatomic locations were significantly different between the 2 groups.
Their mean follow up time after dental implantation was 3 years (range, 6 months
to 9 years). Kaplan-Meier survival estimates showed 97.8% probability of survival
up to 9 years in the delayed placement group and 100% probability of survival up
to 8 years in the immediate placement group. There was no significant difference
in implant survival according to the time of implantation. No significant
difference in cervical bone loss (CBL) at the mesial or distal side was found
between the 2 groups. CBL according to anatomic location, the type of prosthesis,
or gender was not significantly different either between the 2 groups. However,
CBL at distal side of 1-stage approach was significantly (P < .05) smaller in the
delayed placement group than that in the immediate placement group. CONCLUSION:
This study showed that immediate dental implantation in molar and premolar
regions had good clinical and radiographic outcomes.
PMID- 28517554
TI - SU-E-J-08: Dependence of Imaging Dose on Image Quality of Free-Breathing 3DCBCT
of Moving Tumors.
AB - PURPOSE: To evaluate the impact on free-breathing CBCT (FBCBCT) image quality to
properly visualize the motion range of moving tumors as a function of imaging
dose. METHODS: A multi-purpose body phantom (QUASAR) with a cylindrical cedar
wood (density = 0.330g/cc), and an embedded 3-cm diameter Polystyrene sphere
(density = 0.855g/cc) were used to simulate lung tumor motion. Varian Trilogy
with OBI system was used to acquire CBCT images (high-dose mode: 125kVp, 80mA,
25ms/frame & low-dose mode: 110kVp, 20mA, 20ms/frame). As the FBCBCT projections
were acquired, the sphere moved in accordance to 30 simulated sinusoidal patient
breathing patterns using a programmable motion platform, which were given the
parameters: inhalation-to-exhalation (I/E) ratio ranging from 1-0.2131,
amplitudes of 1 and 3 cm, and periods 2, 4, and 6 seconds. Following the
acquisition of FBCBCT images, the ITV contrast, defined as = (target pixel values
inside the sphere - avg. pixel values in background)/(avg. pixel values in
background), were calculated per image slice. RESULTS: All parameters, I/E ratio,
period, and amplitude did not seem to have much impact on the percentage change
of the ITV contrast as a function of imaging dose. The percentage-change for all
coronal images with a reduced ITV contrast when going from high-dose to low-dose
was - 4.61 +/- 3.04%, while the percentage-change for all coronal images with an
ncreased ITV contrast when going from high-dose to low-dose, was 8.19 +/- 3.61%.
The overall percentage-change of all 30 coronal images was 5.21 +/- 6.49%.
CONCLUSIONS: We found that imaging dose did not have much impact on the
visibility of the ITV volume, irrespective of the amplitude, I/E ratio, or
period. Thus, it seems that low-dose FBCBCT may be just as suitable for clinical
use while sparing a significant imaging dose to the patients.
PMID- 28517553
TI - IFI16 reduced expression is correlated with unfavorable outcome in chronic
lymphocytic leukemia.
AB - Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. Its
clinical course is typically indolent; however, based on a series of
pathobiological, clinical, genetic, and phenotypic parameters, patient survival
varies from less than 5 to more than 20 years. In this paper, we show for the
first time that the expression of the interferon-inducible DNA sensor IFI16, a
member of the PYHIN protein family involved in proliferation inhibition and
apoptosis regulation, is associated with the clinical outcome in CLL. We studied
99 CLLs cases by immunohistochemistry and 10 CLLs cases by gene expression
profiling. We found quite variable degrees of IFI16 expression among CLLs cases.
Noteworthy, we observed that a reduced IFI16 expression was associated with a
very poor survival, but only in cases with ZAP70/CD38 expression. Furthermore, we
found that IFI16 expression was associated with a specific gene expression
signature. As IFI16 can be easily detected by immunohistochemistry or flow
cytometry, it may become a part of phenotypic screening in CLL patients if its
prognostic role is confirmed in independent series.
PMID- 28517555
TI - SU-E-J-45: Validation of the ExacTrac Virtual Isocenter Based Target Localization
Method.
AB - PURPOSE: With no stable landmarks available for localization, a 'virtual
isocenter' "'or surrogate landmark near the target'" can be used for image
guidance. However, using a virtual isocenter in ExacTrac has not been thoroughly
validated. This study evaluates its target localization accuracy and investigates
the impact of two different couch correction sequences. METHODS: A CT scan was
acquired on an anthropomorphic thoracic phantom with a 2mm-diameter ball bearing
(BB) marker implanted in thelung region. A treatment plan was created with
isocenter placed at the BB center, and exported to ExacTrac. In ExacTrac, a
virtual isocenter wasplaced on a spine vertebral body where three translational
shifts (8.8cm laterally, 1.5cm longitudinally and 6cm vertically) were present. A
series ofcouch rotations (+/-3 degrees, 1 degree increment) was intentionally
applied to simulate angular setup variations. For each rotation, two stereoscopic
x-rayimages were acquired and fused using the ExacTrac 6D registrationalgorithm.
Calculated shifts were applied using two sequences: (1)automatic 5D corrections
(three translations/two robotic couch rotations) followed by manual couch
rotation; (2) manual couch rotation then automatic 5D corrections. After each
ExacTrac localization, orthogonal (anterior-posterior and right-lateral) portal
images were acquired to quantify BB center deviations from the radiation
isocenter as an indicator of residual error. RESULTS: Minimal difference between
investigated table correction sequences was observed. Average translational
deviations between the BB and radiation isocenter (mean+/-1SD) were 0.3+/-0.3mm
and 1.0+/-0.2mm for lateral and vertical axis respectively. Longitudinally, the
deviations were 0.8+/-0.4mm from the anterior-posterior image and 0.1+/-0.3mm
from the right-lateral image. The systematic difference (0.7+/-0.1 mm) between
thetwo may have been attributed to gantry sagging during rotation. CONCLUSIONS:
ExacTrac system successfully corrected angular shifts using the virtual isocenter
method in a rigid phantom setup. The sequence ofcouch correction did not
influence the localization accuracy. Further patient study is warranted.
PMID- 28517556
TI - SU-E-J-18: Evaluation of the Effectiveness of Compression Methods in SBRT for
Lung.
AB - PURPOSE: This study aims to evaluate the effectiveness of compression in
immobilizing tumor during stereotactic body radiotherapy (SBRT) for lung cancer.
METHODS: Published data have demonstrated bigger respiratory motion in lower lobe
than in upper lobe during normal breathing. We hypothesize that 4DCT-based
patient selection and abdominal compression would immobilize lung tumor volumes
effectively, regardless of their location. We retrospectively reviewed 12 SBRT
lung cases treated with Trilogy(r) (Varian Medical System, Palo Alto, CA). Either
compression plate or Vac-LokTM was used as abdomen compression of the SBRT
immobilization system (Body Pro-LokTM, CIVCO) to restrict patients' breathing
during CT simulation and treatment delivery. These cases are grouped into 2
categories: lower and upper lobe tumor, each with 6 cases. Records for 33
treatments were studied. On each treatment day, the patient was set up to the
bony anatomy using kV-kV-match. A CBCT was performed to further set up the
patient to the tumor based on the soft tissue information. The shifts from CBCT
setup were analyzed as displacement vectors demonstrating the magnitude of the
tumor motion relative to the bony anatomy. RESULTS: The mean magnitude of
displacement vectors for upper lobe and lower lobe were 3.7+/-2.7 and 4.2+/-6.3,
[1S.D.] mm, respectively. The Wilcoxon rank sum test indicates that the
difference in the displacement vector between the two groups is not statistically
significant (p-value = 0.33). CONCLUSIONS: The magnitude of shifts from CBCT were
small with mean value <5mm in SBRT lung treatments. No statistically significant
difference were observed in the displacement of tumor between lower and upper
lobes. With limited sample size, this suggests that our current 4DCT
screening/abdominal compression approach is effective in restricting the
respiration-induced tumor motion despite its location within the lung. We plan to
confirm this Result in additional patients.
PMID- 28517557
TI - SU-E-J-56: Localization Error in Gamma Radiosurgery with 3T MR Due to Fiducial
Box Chemical Shift from Incorrect Liquid Filling Materials.
AB - PURPOSE: Use of a 3D MAGIC (Methacrylic and Ascorbic acid in Gelatin Initiated by
Copper) polymer gel dosimeter to evaluate potential localization and positioning
errors due to the use of incorrect liquid filling material (baby oil instead of
copper sulfate) for a gamma radiosurgery (GSR) MRI fiducial box. METHOD AND
MATERIALS: Two phantoms were used to evaluate geometric errors due to chemical
shift for 'baby oil' fiducial markers: 1) a cylindrical grid phantom with Teflon
rod insert; 2) a human skull phantom with a MAGIC (Gelatin 9%; Methacrylic acid
4%; CuSO4 0.1mM; Ascorbic acid 2mM; Glucose 10%) gel capsule to simulate an
intracranial target. Both phantoms were stereotactically MR and CT scanned for
GSR treatment planning using a 'baby oil' GSR MRI fiducial box and a standard CT
fiducial box. The gel capsule was given 15Gy @ 50% isodose line using the
4mmcollimator based on 'baby oil' fiducial box MR images. Then, the skull phantom
with capsule was scanned in 3T GE Signa(r) EXCITETM clinical scanner (Spin Echo
pulse sequence) for 3D dose distribution read-out. Dose distribution errors were
analyzed based on gel results for the combined MR and CT plans. For comparison,
deviation of grid phantom teflon rods were directly measured from MR and CT
stereotactic images. RESULTS: Gel dose profile measurements indicate a 3.8mm
shift in the phase encoding direction for the 'baby oil' fiducial marker for 3T
MRI based GSR treatment planning. A 3.7mm shift in Teflon rod position was also
confirmed through direct comparison of CT and MR images. CONCLUSION: Both results
showsignificant target localization and positioning errors can be caused if
inappropriate filling materials are used for GSR MRI fiducial boxes. Thisstudy
also indicates that MAGIC polymer gel can be used as a versatile toolfor GSR 3D
quality assurance.
PMID- 28517558
TI - SU-E-J-29: Evaluation of Effectiveness of Immobilization Devices for Radiation
Therapy with Repeated CBCT Studies.
AB - PURPOSE: To evaluate the effectiveness of three different immobilization devices
for lung radiation therapy with daily and/or weekly cone-beam CTs (CBCT).
METHODS: Three different immobilization devices, short (IM1) and long (Im2 ) Vac
lok cushion with wing boards (Civco), BodyFix (Im3 , Elekta), were investigated.
Repeated CBCT images for 3 SBRT patients immobilized with Im3 , and 6 IMRT
patients immobilized with IM1 and Im2 (3 each) were acquired. Each SBRT patient
received 70 Gy in 10 fractions and setup daily with CBCT, while IM1 and Im2
patients were setup daily with orthogonal kV, and weekly CBCT (week 0-6). The day
1, 6 and 10 CBCT for Im3 were considered week 0-2 CBCT. Patient setup was first
based on skins markers then shifts were made based on bony landmarks in kV and
GTV with CBCT. Skin contours, which are further away from the isocenter and thus
more sensitive to rotation and skin folding, were extracted in each CBCT data set
and the difference on skin contours were investigated for both before and after
shifts. RESULTS: Over 2 weeks of treatment, Im3 has the smallest standard
deviation for setup shifts (0.09, 0.16, 0.20 cm on LR, UD and IO directions)
compared to IM1 (0.29, 0.35, 0.34 cm) and Im2 (0.11, 0.19, 0.40 cm), which
indicates setup based on skin markers were the most reproducible for Im3 . Over 6
weeks of treatment, Im2 (0.16, 0.18, 0.42 cm) is more reproducible than IM1
(0.44, 0.45, 0.35 cm). All 3 patients with IM1 and 2 patients with Im2 were found
to have >1 cm difference in skin contour even after shifts were made. 1 patient
with IM1 was found to have non-reproducing skin folding of >3 cm difference.
CONCLUSIONS: Information derived from repeated CT images could be used to
evaluate the effectiveness of the immobilization devices.
PMID- 28517559
TI - SU-E-J-38: Rotational Setup Errors in Pediatric Patients Receiving Radiation
Therapy for Intracranial Tumors.
AB - PURPOSE: We have clinically observed that larger rotational setup errors are more
prominent in pediatric patients who received radiation therapy for brain tumors.
In this work, we quantitatively evaluated the daily setup corrections in pitch,
roll, and yaw axes for children who received intracranial radiation therapy under
x-ray image guidance. METHODS: Daily localization data of 43 patients between the
ages of 10 months and 21.9 years were analyzed in this study. Patients were
immobilized with thermoplastic mask during treatments, and 2D orthogonal x-ray
images wereacquired for setup corrections before each treatment. Rotational setup
corrections in pitch, roll, and yaw axes were extracted from 873 treatment
fractions, and were analyzed for the whole group of patients and for two age
groups: < 5 and = 5 years old. RESULTS: The mean values for the pitch corrections
were 1.91 degrees and 1.65 degrees (p:0.02), roll corrections were 1.37 degrees
and 1 degrees (p<0.001), and yaw corrections were 1.93 degrees and 1.47
degrees (p<0.001), respectively. For patients < 5 years, 21.7% of treatments had
pitch corrections more than 3 degrees , versus 15.6% of treatments required pitch
corrections more than 3 degrees for patients >= 5 years. Similarly, 10.6% of
roll corrections and 20.9% of yaw corrections were more than 3 degrees for
patients < 5 years. On the other hand, 2.1% of roll and 13.8% of yaw corrections
were more than 3 degrees for patients = 5 years old. CONCLUSIONS: Data indicate
that children less than 5 years old are more prone to rotational setup errors
during intracranial radiation therapy. This can be attributed to reduced efficacy
of immobilization devices due to smaller and rounder anatomicalfeatures of
pediatric patients, and challenges in setup while the patient is under
anesthesia. The role of daily image guidance and rotational setup corrections
becomes important to ensure target coverage, especially for children < 5 years
old.
PMID- 28517560
TI - SU-E-J-11: Characterization of Interfractioanal Anatomical Variations in Post
Operative Radiation Therapy for Prostate Bed.
AB - PURPOSE: To quantitatively characterize the interfractional anatomic variations
in post-operative radiation therapy (RT) for prostate bed, so that appropriate
strategy that can fully address these variations can be developed. METHODS: A
total of 102 daily pre-treatment CT acquired using an in-room CT (CTVision,
Siemens) for 10 patients treated with post-operative IG-IMRT of prostate bed.
Prior to each fraction, patients were repositioned to correct for interfractional
translational shifts based on the alignment of both anterior rectal wall and
surgical clips between the daily CT and the planning CT. The PTV was assumed to
be the volume enclosed by the 95% prescription isodose surface generated for the
conventional four field box. Contours of the PTV, rectum and bladder on each
daily CT were generated by populating the planning contours using an auto
segmentation tool based on deformable registration (ABAS, Elekta) with manual
editing. Interfrcational variations in the volumes, shapes and positions of these
contours were obtained. The displacement of the center of mass (DCOM) with
respect to the isocenter was used to measure interfractional organ motion, and
the maximum overlap rate (MOR) was used to measure organ deformation. RESULTS:
Interfractional variations in the volumes of rectum and bladder were in the range
of 50-270% (average 116+/-41%) and 30-180% (average 67+/-26%), respectively. The
averages of DCOM for rectum are: - 0.35+/-0.46cm (lateral, varying from -1.58 to
1.23cm), -0.33+/-0.99cm (longitudinal, varying from -2.4 to 1.8cm), and -3.41+/
1.14cm (vertical, varying from -5.56 to -0.99cm). These values for bladder are:
0.20+/-0.50cm (lateral, varying from -1.48 to 0.61cm), 3.63+/-1.10cm
(longitudinal, varying from -5.7 to 3.1cm), and -0.31+/-0.97cm (vertical, varying
from -1.68 to 2.77cm). CONCLUSIONS: Large interfractional changes in organ
volumes, shapes and positions are seen in post-operative RT for prostate bed.
These changes cannot be accounted for by the current standard practice of IGRT
repositioning. This work is supported partially by MCW Cancer Center Fotsch
Foundation.
PMID- 28517561
TI - SU-E-J-49: Reliability Study of ExacTrac- System Image Isocenter Using an On
Demand QA Procedure.
AB - PURPOSE: To develop a pointer based quality assurance (QA) procedure that quickly
verifies the congruence of ExacTrac(r) image isocenter with the radiation
isocenter of a linear accelerator (linac), and use it to study the accuracy and
reliability of the ExacTrac(r) image isocenter. METHOD AND MATERIALS: A 6 mm
diameter tungsten ball was aligned with the room laserusing a pointer alignment
system. By measuring the positions of ExacTrac(r)image isocenter and linac
radiation isocenter relative to the ball, thedeviations between the two
isocenters was easily calculated. The ExacTrac(r)image isocenter relative to the
ball was measured using the built-in Winston-Lutz Pointer test, in which kV
images of the ball are projected to flat panels and the center of the ball to the
image isocenter are calculated by ExacTrac(r) software. The linac radiation
isocenter relative to the ball was measured by taking the portal images of the
ball at four gantry angles, 0,90, 180 and 270 with a 6 * 6 cm2 field. An in-house
developed software was used to identify the center of the ball and the center of
the radiation. This procedure was used in weekly QA for a year in this work.
RESULTS: A simple QA procedure was developed to ensure the accuracy of
ExacTrac(r) imageisocenter against the linac radiation isocenter. The procedure
can be executed in less than 20 minutes. The data show the position error were -
0.27+/-0.30, 0.52+/-0.24, 0.18+/-0.22 mm in the lateral, vertical and
longitudinal directions, and the max deviation were 0.86, 0.89 and 0.54 mm
respectively. CONCLUSION: The weekly verification data showed the ExacTrac(r)
image isocenter can be very reliable with sub-millimeter accuracy. This level of
imaging alignment accuracy is necessary for imaging guided SBRT procedures. The
quick QA procedure can be applied on-demand to ensure the accuracy of ExacTrac(r)
isocenter.
PMID- 28517562
TI - SU-E-J-22: Effect of MLC Leaf Width on MLC Leaf Shifting Algorithm for Concurrent
Treatment of Prostate and Pelvic Lymph Nodes.
AB - PURPOSE: Our previous study showed that adjusting selected MLC leaf pairsto
follow prostate movement is an effective strategy to account for daily prostate
displacement during concurrent treatment with pelvic lymph nodes. MLC leaf width
affects the quality of MLC shifting plans for longitudinal prostate motion
compensation. This study is to investigate the effect of the MLC leaf width in
compensation of the prostate movement. METHODS: Fifty-one daily CT on-rail scans
from three patients were available for this study. On these CTs, the prostate,
bladder and rectum were manually contoured, and the lymph nodes contours were
transferred from the planning CT after rigid bony registration. For each patient,
three different IMRT plans were created based on a planning CT using leaf width
of 2.5, 5, and 10 mm, respectively. For each CT, the prostate displacement was
determined by dual imaging registration and compensated by shifting MLC resulting
in a total of 153 MLC shifted plans. RESULTS: Among 51 daily CTs, the average
prostate movement along the superior/inferior direction was 1.1+/-3.7 mm (range:
6 to 6.5 mm). The differences in D99 of the prostate between the dose of the day
and dose of the plan were 2.3+/-3.3%, 1.3+/-2.0%, and 4.4+/-5.1% for 2.5, 5, and
10 mm leaf width plans, respectively (p<<0.05). The corresponding differences in
D99 of the lymph nodes were 0.7+/-0.9%, 0.6+/-0.9%, and 1.4+/-0.8%. The mean
differences in D50 were 0.8%, 1.6%, and 2.7% for the bladder, and 10.0%, 3.9%,
and 5.7% for the rectum, respectively. CONCLUSIONS: Using the MLC Shifting method
to compensate for prostate movement in the longitudinal direction depends on the
MLC leaf width and the magnitude of the prostate motion. The use of leaf width of
5 mm can provide sufficient tumor coverage without significantly affecting doses
to the critical structures.
PMID- 28517563
TI - SU-E-J-60: Comparison of CT-On-Rails and a 3D Surface Imaging System for Image
Guided Pelvic Radiation Therapy for Both Supine and Prone Patient Positions.
AB - PURPOSE: We investigate the feasibility of using AlignRT for pelvic radiation
image guidance. The uniqueness of our study is that all patients have multiple CT
on-rails (CTOR) scans to compare corresponding AlignRT images to. METHODS: Ten
patients receiving pelvic radiation were enrolled in this study. Two simulation
CT scans were performed in supine and prone positions for each patient. Body
surface contours were generated in treatment planning system and exported to
AlignRT to serve as reference images. The patient was aligned to treatment
isocenter with room lasers, and then scanned with both CTOR and AlignRT in both
supine and prone positions. Image guidance shifts were calculated for both
modalities by comparison to the simulation CT and the differences between them
were analyzed. These procedures were performed for each patient once per week for
five weeks. The average and maximum difference of displacement between AlignRT
and CTOR were calculated for each patient. RESULTS: For supine position, there
are 4 patients who had the average difference of displacement between AlignRT and
CTOR along any direction (vertical, longitudinal, and lateral) greater than
0.5cm, and 1 patient greater than 1cm. For prone position, there are 7 patients
who had the average difference greater than 0.5cm, and 3 patients greater than
1cm. For supine position, there are 4 patients who had the maximum difference
great than 1cm. For prone position, there are 9 patients who had the maximum
difference greater than 1 cm. The difference of displacement between AlignRT and
CTOR is greater for prone position than for supine position. CONCLUSIONS: AlignRT
does not appear to be an advisable image guidance approach for pelvic radiation
therapy for patients with either supine or prone position. There appears to be a
potential for large alignment discrepancies (up to 2.25 cm) between AlignRT and
CTOR.
PMID- 28517565
TI - SU-E-J-05: Validation of an Iterative Tomosynthesis Algorithm for Low Dose on
Board Cone Beam CT Patient Localization.
AB - PURPOSE: Cone beam CT (CBCT) is a well established technique to localize patients
using bone and soft tissue anatomy. Current protocols are limited to one weekly
CBCT due to the considerable imaging dose delivered to the patient. The purpose
of this project is to develop and validate a low dose CBCT algorithm to reduce
dose and imaging time of current 3D imaging localization procedures using a novel
iterative tomosynthesis algorithm to allow daily CBCT for patient positioning and
target localization. METHODS: The algorithm is based on the combination of a
tomosynthesis filtered back propagation (TFBP) acquisition geometry algorithm and
a maximum likelihood expectation maximization (MLEM) iterative reconstruction.
Circular or arc acquisition trajectory, projection number, and angular projection
position are optimized according to the anatomical treatment site and region of
interest. The TFBP method provides the first 3D image estimate, and the MLEM
improves its quality. In this study, we focused on head and neck treatment
localization imaging. RESULTS: We studied the performance of our tomosynthesis
algorithm imaging resolution on an anthropomorphic head and neck phantom to
determine image quality as a function of dose reduction techniques. Reconstructed
anatomy shows that a 1/8 dose reduction provides similar image quality and
resolution as current CBCT protocols. Seven iterations show an optimal compromise
between image quality and reconstruction time. Tomosynthesis images provide
digitally reconstructed radiographs with similar resolution and contrast as full
CBCT. We verified that the iterative process eliminates phantom images originated
by the acquired sparse angular data projections. CONCLUSIONS: We developed and
validated an iterative algorithm for low dose cone beam CT based on circular or
arc tomosynthesis geometries and iterative reconstruction techniques. The
algorithm combines the strengths of both techniques to provide a novel low dose
method to image patient anatomy for patient positioning and target localization.
PMID- 28517564
TI - SU-E-J-33: Geometric Agreement Check for Imaging System with Radiation Beam by KV
and MV-CBCT.
AB - PURPOSE: The verification method of the geometry agreement between a light field
and/or a laser coordinate and treatment beam should be easy and quick. In this
presentation, we propose a novel QA method by using both kV- and MV-CBCT for kV
IGRT system. This method confirms the temporal unchanging the agreement of
geometry in the kV-IGRT system with the treatment beam geometry. METHODS: 1) MV
flexmap: Sequential MV-projection images were acquired during gantry rotation by
iViewGT (Elekta) and MV-CBCT was reconstructed by in-house software with a
flexmap correction. The flexmap is displacement of gantry and detector panel
related with gantry sag. The geometric change affects the deranging reconstructed
image. To evaluate how much displacement of EPID panel and gantry was detectable,
the images of 8mm diameter ball-bearing (BB) located at the radiation isocenter
were reconstructed with improper Flexmap.2) A comparison between the kV-CBCT and
the MV-CBCT: The kV-CBCT was provided by X-ray Volume image (XVI) system
(Elekta). To confirm the agreement for the geometry between kV-IGRT system and
treatment beam, the kV-CBCTs of BB are compared with that of MV-CBCTs. RESULTS:
The flexmaps were modified to (b)1mm / (c)3mm shifted to the rotation direction
and (d)3mm to the rotation axis. The MV-CBCT were reconstructed with the correct
flexmap and with incorrect flexmap (b), (c) and (d).a??The geometric confirmation
for MV-CBCT was done by comparison of the width and center of the BB on the MV
CBCT. The discrepancy of center between kV-CBCT and MV-CBCT was less than 1mm.
CONCLUSIONS: Less than 1mm of the geometrical changing to rotation direction for
MV-detector panel could be recognized by reconstructed images of BB. Using kV-
and MV-CBCT enable us to perform the simple comparison for geometrical non
idealities between the kV-IGRT system and the treatment beam. Dr. K. Nakagawa
received research grant from Elekta.
PMID- 28517566
TI - SU-E-J-42: Motion Adaptive Image Filter for Low Dose X-Ray Fluoroscopy in the
Real-Time Tumor-Tracking Radiotherapy System.
AB - PURPOSE: In the real-time tumor-tracking radiotherapy system, fiducial markers
are detected by X-ray fluoroscopy. The fluoroscopic parameters should be
optimized as low as possible in order to reduce unnecessary imaging dose.
However, the fiducial markers could not be recognized due to effect of
statistical noise in low dose imaging. Image processing is envisioned to be a
solution to improve image quality and to maintain tracking accuracy. In this
study, a recursive image filter adapted to target motion is proposed. METHODS: A
fluoroscopy system was used for the experiment. A spherical gold marker was used
as a fiducial marker. About 450 fluoroscopic images of the marker were recorded.
In order to mimic respiratory motion of the marker, the images were shifted
sequentially. The tube voltage, current and exposure duration were fixed at 65
kV, 50 mA and 2.5 msec as low dose imaging condition, respectively. The tube
current was 100 mA as high dose imaging. A pattern recognition score (PRS)
ranging from 0 to 100 and image registration error were investigated by
performing template pattern matching to each sequential image. The results with
and without image processing were compared. RESULTS: In low dose imaging,
theimage registration error and the PRS without the image processing were 2.15+/
1.21 pixel and 46.67+/-6.40, respectively. Those with the image processing were
1.48+/-0.82 pixel and 67.80+/-4.51, respectively. There was nosignificant
difference in the image registration error and the PRS between the results of low
dose imaging with the image processing and that of high dose imaging without the
image processing. CONCLUSIONS: The results showed that the recursive filter was
effective in order to maintain marker tracking stability and accuracy in low dose
fluoroscopy.
PMID- 28517567
TI - SU-E-J-15: Calculating the Dose from KV Cone Beam CT Within and Outside the
Treatment Volume Using a Treatment Planning System.
AB - PURPOSE: To assess the dose from kilovoltage cone beam CT from two image
acquisition protocols, pelvis and head and neck, by addition of the dose to the
patient treatment plans. METHODS: A total of 20 patients (10 pelvis and 10 head
and neck) undergoing radiation therapy were selected and the dose from kV CBCT
was calculated using a treatment planning system previously commissioned for this
purpose. The imaging dose was added to the CT images used for treatment planning.
Daily shifts as a Result of imaging were recorded and applied to imaging beam
whenever the sum of the shifts exceeded 0.5 cm. The kV CBCT dose can also be
computed prior to planning, in case of IMRT treatments, and used during
optimization. RESULTS: The additional dose as a Result of daily CBCT is in the
order of few cGy for head and neck and up to 90 cGy for the pelvis cases using
the standard head and neck and pelvis protocols. The pelvic dose is especially
dependent on patient size, being higher for smaller patients. Due to the low
energy of the kV CBCT beam, the maximum energy deposition is at or near the
surface with the highest dose being on the patient's left side for the head and
neck and on the posterior for the pelvic cases. CONCLUSIONS: Dose from daily
kilovoltage CBCT can be added to patient treatment plans using previously
commissioned kV CBCT beams in a treatment planning system. In the case of IMRT
planning, optimization can be done accounting for kV CBCT dose.
PMID- 28517568
TI - SU-E-J-53: A Phantom Validation Study of a 3D Background Phase Model for MR
Thermometry.
AB - PURPOSE: The proton resonance frequency (PRF) shift method is the most widely
accepted method for magnetic resonance thermal imaging to provide real-time
treatment monitoring of thermal therapies. However, the PRF shift technique
involves the subtraction of a reference phase map, which causes the technique to
be easily perturbed by tissue motion and other background contaminations. In this
study, a three-dimensional background phase is estimated in order to create a
phase reference for each time point. METHODS: A magnetic resonance spectroscopy
(MRS) sphere was scanned within a 3T MRI scanner employing a 3D fast SPGR
sequence. Real and imaginary images were acquired to obtain phase images as the
control. The ability to predict the background phase was investigated by
systematically removing phase information from the control data set. Data was
initially removed from a spherical region of interest (ROI) to simulate a region
where ablativeheating would take place. In a second case, the same spherical ROI
was removed as well as every other slice to further reduce the amount of existing
data. A 3D finite element model was implemented to solve the Dirichlet problem
given a measured phase on the boundary of the simulated available data. RESULTS:
Line profiles taken through the phantom indicate phase estimates to compare well
with actual phase measurements. The phase estimation still shows good agreement
when reducing the amount of data to every other slice. CONCLUSIONS: The 3D multi
slice temperature estimate potentially provides a robust technique that is not as
susceptible to through-plane or in-plane motion-induced temperature artifacts as
compared to thecurrent PRF shift method. The research in this paper was supported
in part through 1R21EB010196-01.
PMID- 28517570
TI - SU-E-J-17: Evaluation of Metal Artifact Reduction in MVCTs Using a Model Based
Image Reconstruction Method.
AB - PURPOSE: To evaluate the performance of a model based image reconstruction in
reducing metal artifacts in MVCT systems, and to compare with filtered-back
projection (FBP) technique. METHODS: Iterative maximum likelihood polychromatic
algorithm for CT (IMPACT) is used with pair/triplet production process and the
energy dependent response of detectors. The beam spectra for in-house bench-top
and TomotherapyTM MVCT are modelled for use in IMPACT. The energy dependent gain
of detectors is calculated using a constrained optimization technique and
measured attenuation produced by 0 - 24 cm thick solid water slabs. A cylindrical
(19 cm diameter) plexiglass phantom containing various central cylindrical
inserts (relative electron density of 0.28-1.69) between two steel rods (2 cm
diameter) is scanned in the bench-top [the bremsstrahlung radiation from 6 MeV
electron beam passed through 4 cm solid water on the Varian Clinac 2300C] and
TomotherapyTM MVCTs. The FBP reconstructs images from raw signal normalised to
air scan and corrected for beam hardening using a uniform plexi-glass cylinder
(20 cm diameter). IMPACT starts with FBP reconstructed seed image and
reconstructs final image at 1.25 MeV in 150 iterations. RESULTS: FBP produces a
visible dark shading in the image between two steel rods that becomes darker with
higher density central insert causing 5-8 % underestimation of electron density
compared to the case without the steel rods. In the IMPACT image the dark shading
connecting the steel rods is nearly removed and the uniform background restored.
The average attenuation coefficients of the inserts and the background are very
close to the corresponding theoretical values at 1.25 MeV. CONCLUSIONS: The dark
shading metal artifact due to beam hardening can be removed in MVCT using the
iterative reconstruction algorithm such as IMPACT. However, the accurate
modelling of detectors' energy dependent response and physical processes are
crucial for successful implementation. Funding support for the research is
obtained from "Vanier Canada Graduate Scholarship" and "Canadian Institute of
Health Research".
PMID- 28517571
TI - SU-E-J-55: Development of a Novel Cableless Radiolucent RF Coil for MR-Guided
Radiation Therapy (MRgRTTM).
AB - PURPOSE: To demonstrate the feasibility of a novel radiotherapy-compatible
cableless radiofrequency (RF) coil for an MR-guided radiation therapy(MRgRTTM)
system that employs a movable MRI system. This coil technology will expedite
clinical workflow by eliminating need for coil connections and cables, allowing
RF coils to remain in place for treatment. METHODS: We quantified radiation
transmission factors and surface dose changes for aluminum (Al), copper (Cu) and
FR4 substrate typical of RF coils using a Varian Trilogy linear accelerator. Ion
chamber measurements were performed by applying 6 MV fields of various sizes
through sheets of each material and metal-substrate combination. These
measurements were repeated with the materials on a standard treatment couch.
Material optimization provided input to build a prototype cableless coil and
representative coil segment for surface dose measurements. RESULTS: We observed
expected patterns for radiation field sizes between 1 cm * 1 cm and 25 cm * 25 cm
and expected variation with off-axis distances < 12 cm. All metal-substrate
combinations had transmission factors > 0.996, the lowest being Cu-FR4. Relative
surface dose increases were similar for Cu-FR4 (3.9) and Al-FR4 (3.3)
combinations. Couchtop relative surface dose increases were much greater than
coil materials alone and did not increase substantially with the addition of coil
materials (couch-only = 6.6, couch with Cu-FR4 = 7.3). Relative surface dose
increase was 6.23 for prototype coil segment with capacitor, but the capacitors
are not in the primary beam path for the coil design. CONCLUSIONS: Results
indicate surface dose effectsare the dominant consideration in RF coil design for
MRgRT. Similar Cu and Al surface dose effects suggest Cu is a viable coil
inductor material for this application. Given that coil material contribution to
surface dose is small compared to the couchtop material it is feasible to keep
this cablelesscoil in place during radiation treatment. This work has received
research personnel support from IMRIS.
PMID- 28517569
TI - SU-E-J-26: Automated Estimation Method of Patient Setup Errors Using Simulated
Portal Images for Prostate Cancer Radiotherapy.
AB - PURPOSE: We developed a novel automated estimation method for patient setup
errors based on simulated and real portal images for prostate cancer
radiotherapy. METHODS: The estimation of patient setup errors in this study was
based on a template matching technique with a cross-correlation coefficient and
Sobel filter between the real portal image and localized pelvic template of
reference image, which were DRR (digitally reconstructed radiography) images and
simulated portal images. The simulated portal image was derived by projecting a
CT image according to an inverse exponential power law of x-ray attenuation for a
water-equivalent path length of each voxel of the CT image on each ray from a
source to each pixel on the EPID (electric portal imaging device). A localized
pelvic template of each patient in AP (anterior-posterior) or lateral view was
automatically extracted from the DRR or simulated portal images by cropping a
rectangular region, which was determined by using the mean pelvic template and
four anatomical feature points. We applied the proposed method to three prostate
cancer cases, and evaluated it using the residual error between the patient setup
error obtained by proposed method and the gold standard setup error determined by
two radiation oncologists. RESULTS: The average residual errors of the patient
setup error for the DRR and simulated portal images were 0.79 and 1.26 mm in the
left-right (LR) direction, 3.17 and 2.05 mm in the superior-inferior (SI)
direction, 1.69 and 5.82 mm in the anterior-posterior (AP) direction, 3.84 and
6.94 mm in Euclidean distance (ED), respectively. If we used the simulated portal
image for LR and SI directions and the DRR image for AP direction, the Euclidean
distance was 3.22 mm. CONCLUSIONS: The proposed method has a potential to
correctly estimate patient setup errors for prostate cancer radiotherapy.
PMID- 28517572
TI - SU-E-J-28: Comparison of IGRT Shift Data Between Prostate Gland and Prostate Bed
Obtained from Ct-On-Rails.
AB - PURPOSE: The daily shifts of prostate gland have been intensively reported in
literatures. However, few papers reported daily shifts of prostate bed due to
several practical difficulties (e.g. limited soft tissue contrast in MVCT and
CBCT and significant deformation of prostate cavity). We have routinely performed
IGRT for both prostate gland and bed with ct-on-rails, and the superior image
quality allows us not only to differentiate both bony anatomy and soft tissue
contrast of prostate gland and bed. In this study, we investigated if the shift
of prostate bed is signifiant difference from that of prostate gland. METHODS: we
reviewed shift data of 50 prostate gland patients who underwent 43 fractions and
22 patients of prostatectomy underwent 37 fractions. In total 2150 CT scans were
reviewed for prostate gland and 814 scans for prostate bed. RESULTS: Of the
reviewed 814 CT images from 22 prostate bed patients, the standard deviation of
shift was found to be 5.9 mm in AP direction (ranges from -22.4mm to 22mm), 3.2mm
in SI direction (ranges from -14mm to 14mm), and 4.1mm in lateral direction
(ranges from -15mm to 22mm). Of the 2150 CT images of prostate gland from 50
patients, the standard deviation of the shift was found to be 5.4 mm in AP
direction (-20mm to 18 mm), 5.0mm in SI direction (-26mm to 20mm), and 4.3mm in
lateral direction (range from-15 to 30mm). F tests of systematic /random shift
distribution in three orthogonal directions between prostate gland and prostate
bed were subsequently performed, it was found that the systematic shift in SI
direction for prostate bed is smaller than for prostate gland (p=0.003).
CONCLUSIONS: Our result suggests no significant difference existing in shift
between prostate bed and gland. Therefore strategies for daily prostate gland
motion can be directly applied to prostate bed.
PMID- 28517573
TI - SU-E-J-37: Radiation Dose during Chemoembolization: A Predictive Model.
AB - PURPOSE: To identify variables correlated with radiation dose during hepatic
chemoembolization, quantify their individual impact, and apply these findings to
build a dose prediction model. METHODS: A retrospective review of 77 patients
undergoing hepatic chemoembolization between 1/2010-10/2010 was performed.
Variables included: Radiation dose metrics[DAP, CD, number of cone beam CT and
fluoroscopy time] and clinical parameters(BMI, session number, extrahepatic
embolization, lesion number, chemoembolization regimen and lobe(s) treated). CD
was the primary outcome measurement used for the dose model. Univariate and
multivariate linear regression models were used to assess the association between
dose metrics and predictive variables and assess the relative impact of each
variable on dose. Variables were considered statistically significant at the
p<0.05 level. Coefficient of determination(R2)and root mean square error(RMSE)
were calculated for CD. R2 was used to evaluate goodness of fit and RMSE was used
to establish a measurement of the typical size of the error in predicting the
cumulative dose. RESULTS: Based on the multivariate analysis: higher BMI,
regimen, single lesions, 1 degrees tumor and initial session were statistically
significant and incorporated into the following dose prediction model: Predicted
Dose(mGy)= -672+BMI(56.3)+558(session #1)+1789(extrahepatic a. embolized)+232(1
degrees tumor)+[-667(2-4 lesions)or - 12(>5 lesions)]+[370(dox-bead regimen)or
1618(ethiodol based regimen)]. Plots of the predicted vs actual CD were performed
and the adjusted R2 for CD is 52.9%(RMSE = 697). The model is accurate at
predicting 52% of the variation. When the model predicts a dosage of 1000 or 2000
mGy the actual dose interval ranges from 519-2519 mGy or 384-3616 mGy,
respectively. CONCLUSIONS: Creating a radiation dose prediction model is
feasible. This is the first known attempt at creating a dose model for image
guided intervention and refinements to the model will be required to improve its
accuracy. Prospective dose modeling will become more relevant as the cost benefit
analysis of radiation exposure enters the decision making process in patient
care. Alda Tam: Angiodynamics Inc., research funding Joseph Steele: MedicaSafe,
Inc ownership Intelliject medical ownership INTIO medical consultant/ownership
Caymus Medical ownership Cayenne Medical ownership.
PMID- 28517574
TI - SU-E-J-10: Accuracy of Image Guidance Using Cone-Beam CT with Multiple Breath
Hold Using Active Breathing Coordination.
AB - PURPOSE: To complete a CBCT for a treatment using ABC, multiple breath hold (BH)
(>3) were used due to the slow gantry rotation and the short BH period. Inter-BH
tumor position variability may introduce distortion in the reconstructed images.
This study aims to determine a threshold of the inter-BH scan displacement so
that the inconsistency can be identified from the CBCT images. METHODS: A
numerical phantom was constructed to represent the thorax region of a human body.
To simulate the inter-BH displacements, known magnitudes of motion (s = 0, 1, 3,
5 mm) along the longitudinal direction were introduced for the 'tumor' and
'diaphragm' in the phantom. Two different irregular motion patterns (s1=s3=/=s2
and s1=/=s2=/=s3) during CBCT scans were tested. Furthermore, a physical phantom
with a movable insert was scanned using a commercial CBCT system. The insert of
the phantom was programmed to move in the longitudinal direction according to the
same motion patterns as designed in the numerical simulations. Subsequently, nine
CBCT's in 'half-fan' mode for the physical phantom were acquired with the insert
in various positions. These CBCT images were then fused to the reference CT by
aligning to either the body of the phantom or the 'tumor' inside the insert.
RESULTS: Based on numerical simulation, position variation >1mm can be observed
from the reconstructed CBCT images. Based on acquired CBCTs of the physical
phantom, position variations of >3mm or 5mm were observed, depending on the
motion pattern during the data acquisition. Because of the use of half-fan mode,
we observed the order of position displacements of the tumor during CBCT
acquisition drastically affected the outcome of imaging registration.
CONCLUSIONS: Using ABC device, the inter-BH variability during a CBCT acquisition
affects accuracy of tumor localization. A patient individualized planning margin
might be necessary to account for this effect.
PMID- 28517575
TI - SU-E-J-48: Real Time Image Guided Localization in SBRT Lung/Liver Patients
Radiation Treatment.
AB - PURPOSE: Stereotactic body radiation therapy (SBRT) lung/liver patientradiation
treatment requires high precision of patient position and target localization.
For SBRT lung/liver patients positioning, cone beam CT imaging has been widely
used, generally with zero couch rotation. The purpose of this study is to
implement Stereotactic radiation surgery (SRS) patient positioning technology to
SBRT by expanding patient positioning with couch rotation. METHODS: A Varian(r)
Novlis Tx for SRS treatment wasused to treat SBRT lung/liver patients
implementing CBCT. BrainLAB(r) X-ray imaging system in conjunction with optical
guidance is primarily used for SRS patients. CBCT and X-ray imaging system were
independently calibrated with 1.0 mm accuracy. The X-ray imaging system was
implemented through BrainLAB(r) ExacTrac system with CBCT localized position at
the initial zero position for the X-ray imaging system. For the other couch
positions, X-ray images were fused with patient DRRs for positioning. RESULTS:
Based on daily imaging QA records for a period oftwo years, the longitudinal,
vertical and lateral coordination between CBCT and X-ray imaging average 0.3+/
0.5, 0.2+/-0.5 and 0.5+/-0.5 mm. The shiftfrom the CBCT imaging isocenter to the
X-ray imaging isocenter is 0.5+/-0.5 mm accuracy for a 24-month period of
tracking. Patient position accuracy: After initially localizing the patient with
CBCT at the zero couch position, the patient was positioned with the X-ray
imaging system. The computed translational and rotational shift accuracy are
0.5+/-0.5 mm and0.4+/-0.3 degree respectively, based on 66 SBRT lung/liver
patients couchrotations. CONCLUSIONS: Accurate coordination of CBCT and X-ray
imaging in conjunction with optical imaging guidance can be expanded to patient
positioning with couch rotation. The X-ray imaging capability at rotated-couch
positions improved the physician confidence level during SBRT lung/liver patients
treatment.
PMID- 28517576
TI - SU-E-J-21: An Intercomparison of Imaging Performance of Two Linac-Mounted Imaging
Systems Used in Radiation Therapy: TrueBeam and Trilogy.
AB - PURPOSE: To evaluate and compare the performance of the imaging systems of two
linear accelerators, used in radiation therapy. The study includes the following
imaging components: electronic portal imaging device (EPID), kilovoltage
projection imaging and kilovoltage cone-beam CT. METHOD AND MATERIALS: The
imaging systems mounted on the Varian Trilogy (Varian Medical Systems) and Varian
TrueBeam, were evaluated. Image quality of two EPID systems (ASI-1000) and the
two kV flat panel imagers (PaxScan 4030CB) was evaluated in terms of spatial
resolution and contrast-to-noise ratio (CNR) using the QC-3 and QCkV-1 phantoms
(Standard Imaging, Inc.). Cone-beam CT image sets of the CatPhan phantom (The
Phantom Lab.) were obtained for standard dose head (100kVp, 0.4mAs per
projection) and body (125kVp, 1.04mAs) protocols. Imaging parameters of the
default clinical settings were used. The end points of the comparison were
spatial resolution, CT number linearity, low contrast detectability and image
uniformity. Analysis of all types of images was performed by the PIPSpro software
(Standard Imaging). RESULTS: The critical frequency (f50 in units of lp/mm) of
0.446 and 0.403 were obtained for TrueBeam and Trilogy MV detectors,
respectively. The CNR was found double for Trilogy. For kilo-voltage detectors
the f50 was 1.337 and 1.363, while the CNR was better by 6% in Trilogy machine.
The CBCT comparison showed a 30% higher uniformity index for the TrueBeam system
for pelvis protocol and 50% higher head. No significant difference was found in
low contrast detectability and CT number linearity and resolution, 5 lp/mm. The
Trilogy image was noisier by 35% and 30% for pelvis and standard head protocol,
respectively. CONCLUSIONS: The critical frequencies of both kV and MV detectors
were found better in TrueBeam, while CNRs were found better in Trilogy. TrueBeam
preformed superiorly in CBCT in terms of image uniformity and noise level.
PMID- 28517577
TI - SU-E-J-59: Dual Imaging Guided Localization System for Spine Radiosurgery.
AB - PURPOSE: To compare localization accuracies between an ExacTrac and cone beam
computed tomography (CBCT) systems for single fraction spine adiosurgery. The
work also aimed to evaluate the inherent systematic deviation of both ExacTrac
and CBCT systems to achieve highly accurate localization in the spine
radiosurgery. METHODS: ExacTrac and CBCT imaging systems were evaluated using the
linac isocenter as the mutual reference point. First, a BB was placed in an
anthropomorphic pelvic phantom. The phantom was localized with both imaging
systems and the procedure was repeated 12 times. These results were used to
devise a localization protocol using both imaging systems in spine radiosurgery,
and employed for 51 patients (81 isocenters) prescribed for single fraction
treatment. The displacement discrepancy between the isocenter and two systems
were quantified in four dimensions (three translations, one rotation). A
Student's two-tailed t-test was used to test for significant differences between
the two imaging systems. RESULTS: The phantom study showed 1.4+/-0.5, 0.6+/-0.5,
and 0.1+/-0.5 mm differences between the two imaging systems in the
anterior/posterior (A/P), superior/inferior (S/I) and left/right (L/R)
directions, respectively. The angular difference was minimal along all three
axes. The patient study revealed similar isocenter discrepancies between ExacTrac
and CBCT of 1.1 +/- 0.7 mm, 1.0+/-0.9 mm, and 0.2+/-0.9 mm in the A/P, S/I, and
L/R directions, respectively, with the A/P and S/I directions showing statistical
significance ((t(80) = 13.5 and 7.6 respectively, p = 0.000). The couch yaw
discrepancy was 0 +/- 0.3 degrees . Overall, 1 mm systematic differences were
observed in the A/P and S/I directions between ExacTrac and CBCT localization
systems, both in phantom and patient. A procedure was developed to mitigate this
systematic discrepancy. CONCLUSIONS: These findings have justified our patient
localization tolerance levels of 2 mm translation and 1 degree rotation for spine
SRS treatment.
PMID- 28517579
TI - SU-E-J-04: Initial Experience with 4D-CBCT for Lung Cancer: Physician
Verification of Computed Shifts Remains Necessary.
AB - PURPOSE: Four-dimensional cone-beam CT (4D-CBCT) is a novel imaging technique
used to guide treatment setup for patients with pulmonary lesions by providing
additional information about tumor motion at the time of treatment. This study
aimed to evaluate the efficacy of the 4D-CBCT capability in ensuring accurate
patient setup during SBRT. METHODS: Twelve patients with pulmonary lesions were
imaged pre-treatment with Elekta XVI4.5 using the Symmetry protocol resulting in
a respiratory correlated 4D-CBCT. Reconstruction produced 10 phased-based and one
average 3DCT image set. Patient shifts were derived from contour-based(mask)
registration driven by the weighted average of shifts from each phased CT(4D
shifts). Physicians reviewed registration and manually adjusted shifts based on
visual registration. We exported the average 3DCT to MIM Vista Software 5.1.1 in
reference volume coordinates and manually fused to the reference CT. All manual
fusions were contour-based registrations performed by a single observer. No
rotations were permitted in manual fusion to mimic clinical procedure.
Translational 3D shifts from manual fusion were compared to 4D(automatic
registration) shifts and final physician-corrected shifts. RESULTS: Mean
differences between 4D and 3D shifts in lateral, longitudinal, and vertical
directions were 1.07mm, 5.92mm, and 1.43mm, respectively. Mean differences
between physician-corrected and 3D shifts were 1.41mm, 4.83mm, and 1.61mm.
Differences between 4D shifts and 3D shifts increased with increasing tumor
motion. One patient had consistently large longitudinal differences between 4D
and 3D shifts (mean=3.0cm). Further review revealed poor 4D registration(via mask
and clipbox) on the XVI system which was corrected by physician adjustment prior
to treatment. CONCLUSIONS: 4D-CBCT is a valuable imaging tool in patient setup.
Physician review of contour-based registration is imperative in preventing a
geometrical miss. Caution must be employed in tumors that exhibit a large degree
of motion. Further research is necessary in determining functional limits of the
4D-CBCT system.
PMID- 28517578
TI - SU-E-J-32: Evaluation of the Dosimetric Accuracy of Stereotactic Radiosurgery
with Cone-Beam Computed Tomography Localization.
AB - PURPOSE: To evaluate the dosimetric accuracy of stereotactic radiosurgery (SRS)
with cone-beam computed tomography (CBCT) guided patient localization. METHODS: A
Novalis TX linear accelerator with high definition multileaf collimator (HDMLC)
was used for SRS treatments. 20 patients immobilized with the noninvasive
BrainLab U-frame system and thermoplastic mask were selected to evaluate the
dosimetric accuracy of CBCT image-guided SRS by the BrainLab iPlan Phantom
Mapping module. The contours of the PTV and critical organ were transferred
directly from the planning CT and MR images to the CBCT images after image
registrations. The delivered dose distributions could be calculated and analyzed
by copying the original treatment plans to the CBCT images and assigning the
treatment isocenters on the CBCT images according to the couch shifts acquired
after planning CT and CBCT image registrations. The CT electron density
calibration curve used for original plans was also applied for the CBCT-based
planning. RESULTS: The average minimum dose, mean dose, and maximum dose in PTV
of the original plans and the CBCT plans were 95.45%+/-3.80% and 92.88%+/-3.25%,
110.59%+/-1.81% and 110.11%+/-2.40%, 116.55%+/-3.11% and 115.93%+/-2.78%,
respectively. In the original treatment plans, the average 100% prescription dose
coverage of GTV and PTV were 99.99% and 99.81%, respectively. In the CBCT plans,
the average 100% prescription dose coverage of GTV and PTV were 99.90% and
98.20%, respectively. The average conformity index of the original plans and the
CBCT plans were 1.846 and 1.863, respectively. CONCLUSIONS: Data demonstrated
that the dose distributions calculated in the CBCT images were comparable to the
original treatment plans. The CBCT plans only indicated a slightly higher
conformity index and lower average minimum dose, mean dose, maximum dose, GTV
coverage, and PTV coverage compared to the original treatment plans. Therefore,
the CBCT guided localization was considered effective to assure dosimetric
accuracy in SRS.
PMID- 28517580
TI - SU-E-J-41: Fluoroscopy Based Adaptive Setup Approach for Thoracic Cancer IGRT.
AB - PURPOSE: To develop a fluoroscopy imaging based approach that can determine the
magnitude and phase variation in respiratory motion against the treatment
planning images in order to quantify the online patient setup deviation in
thoracic cancer IGRT for the real time adaptive patient positionadjustment.
METHODS: A numerical phantom was generated to test the strength of the approach.
The 2D phantom consist a static outside wall and an inner target moving in
temporal pattern similar to the respiratory motion. Four motion parameters:
frequency (0.5Hz~2Hz), amplitude (40~60mm), position offset (5~10mm), and phase
shift (starting phase 0, 45, and 90 degrees) vary to generate phantom image sets
with different motions. White noise of level SNR=5 was added to all phantom
images to simulate the impact of clinical image quality. A manifold based machine
learning technique was used to construct the respiratory motion model under
thestandard condition (frequency 1 Hz, amplitude 50mm, and no position offset
and/or phase shift). Then the phase and position shift in other phantom image
series were quantified by finding the MAP solution to fit theembedded motion to
the standard motion model. RESULTS: The proposed approach can detect the
variation in motion patterns between two image sets. The method is insensitive to
frequency changes and image noise up to SNR=5, but is very effective at capturing
and quantifying the change in motion amplitude, position shift, and also the
phase shift. CONCLUSIONS: This work proposed an effective mathematical approach
to quantify the difference in motion between the pre-treatment images and the
treatment planning images by extraction of the motion model in fluoroscopy images
using the machine learning technique. By applying the approach during online
patient setup, the positioning deviation can be separated from the respiratory
motion and adjusted to minimize the normal tissue toxicity in gated IGRT.
PMID- 28517581
TI - SU-E-J-14: Evaluation of Mechanical Accuracy of Electronic Portal Imaging Devise
on Its Use in Patient Specific IMRT QA.
AB - PURPOSE: Electronic portal imaging devices (EPID) have been used for both in vivo
dosimetry and in vitro dose verification in intensity modulated radiotherapy
(IMRT). This study is to investigate the effect of EPID mechanical precision on
the accuracy of measured dose distribution. METHODS: EPID energy fluences (dicom
images) of H&N IMRT fields were collected daily on two Varian LINACs (Clinac-iX &
Trilogy) over 4-week period. The energy fluences were converted to doses using
EPIDoseTM (Sun Nuclear Corp). Mechanical deviations of EPIDs could be divided
into two components: one with inherent detector center misalignment from the beam
central axis, another caused by the 'sagging effect' from gantry rotation. The
first component was detected by 'best matching' of the measured and calculated
dose at zero gantry angle (G=0). The second component was computed by 'best
matching' the 10*10cm field defined by MLC at G=0, 90,180, and 270, separately. A
'shift' was generated by the combination of these two components and then applied
to correct the measured dose at the corresponding gantry angle for the IMRT
field. RESULTS: Inherent misalignment of the detector's center and the 'sagging'
deviation were found to be 1-2 mm and 1-5 mm, respectively for both LINACs. Each
component was found very stable (change < 1mm) over the 4-week observational
period. Using a Gamma index of 2%/2mm (DD/DTA), the 'shift' increased the average
passing rate from 59% to more than 92%. On the other hand, blindly applying 'auto
shift' from commercially available software to obtain the best match would
compound true QA issues with units' misalignments. CONCLUSIONS: A false
'mismatch' between measured and calculated dose distribution caused by mechanical
inaccuracies of EPID could be avoided by measuring the two components identified
in this study. One should examine the mechanical precision of equipment prior to
clinical use of EPID dosimetry.
PMID- 28517582
TI - SU-E-J-52: Validation of 3D Structure Projection Onto 2D DRR in Commercial
Treatment Planning Systems.
AB - PURPOSE: The use of structure overlay on setup DRRs can aid the image alignment
procedure for daily image-guided setup procedures. However, the accuracy of a 3D
region-of-interest (ROI) projected on a 2D digitally reconstructed radiograph
(DRR) has rarely been evaluated quantitatively. The goal of this study is to test
the accuracy of two commercial treatment planning systems (TPS) in producing
overlay structures on setup DRRs. METHOD AND MATERIALS: We designed a novel
method to identify landmarks which were on the boundary of the projected ROI on a
DRR. The 3D ROIvolume is composed of a stack of 2D curves. We first
mathematically project each 2D curve onto a beams-eye-view (BEV) plane. Next, we
detectthe boundary points of the projected curves. Those boundary points serve
aslandmarks. Finally, we project the binary mask of the 3D ROI volume using ray
tracing method onto the BEV plane. This projected binary mask is used to exclude
the false landmarks. Once those landmarks are detected, wecompute the distance
between the landmarks and ROI outlines from the TPS. RESULTS: We applied our
validation method to 13 ROIs from a lung patient and 4 simulated ROIs on 2 BEV
DRRs for two different TPS (Eclipse and Pinnacle). Average distance between the
landmarks and ROIoutlines was 0.5mm for both Eclipse and Pinnacle approaches,
which is close to the pixel resolution of the DRR. The maximum distance
andaverage maximum distance was 2mm and 1 mm, respectively, for both TPS.The
maximum distance occurred at points where the ROI curve has a sharpchange between
slices. CONCLUSION: The accuracy of Eclipse and Pinnacle ROI projection method
seems to be acceptable to within 1mm althoughprojection error can be as large as
2mm when structure shape has a sharp variation from one slice to the next.
PMID- 28517583
TI - SU-E-J-25: Dosimetric Characterization of an OBI System Using Gafchromic XRQA2
Film.
AB - PURPOSE: Accurate knowledge about the radiation dose due to the imaging component
of an OBI supported linear accelerator is very important. Though films provide
excellent spatial resolution, there are problems regarding sensitivity and energy
dependence at kV energies. XRQA2 film (0.1-20 cGy) is primarily for measurements
in kV range. We demonstrate their use for absolute dosimetry for an OBI system.
METHODS: H&D curves were generated using a kV therapy x-ray unit in the range of
0-15 cGy. A 25-cm diameter water-equivalent cylindrical phantom with 2.5-cm thick
slabs was used on Varian Trilogy linac. XRQA2 films were cut into circular
diameter and sandwiched between 2 slabs of the cylindrical phantom to measure the
percentage depth dose of the CBCT scans. Additional film pieces were wrapped
around the cylinder for surface dose. To get sufficient signal, 5 CBCT scans were
taken per imaging acquisition template e.g. head standard dose. After 24 hours
post-irradiation, films were scanned using Epson V700 scanner in reflection mode.
Only red channel was used for dosimetric analysis using RIT software. RESULTS:
High-Quality head acquisition template resulted in a dose at 0.2, 1.3, 2.7, and
2.7 cGy on AP, left-lateral, posterior and right-lateral positions of the
phantom, respectively. Low-quality thorax acquisition resulted in 1.4, 1.6, 1.5,
and 1.4 cGy. The PDD at 12.5-cm (isocenter) was of the order of 40%. While the
PDD was fairly uniform from left to right, the PDD along the AP/PA direction were
showing almost continuous fall off with PDD at isocenter of ~40%. Analysis of low
quality head PDDs show little fall off dose with depth though the overall
magnitude was less with PDD at the isocenter only marginally lower than the
maximum along the medial and anterior posterior axis. CONCLUSIONS: Gafchromic
XRQA2 film provides a useful tool to evaluate and characterize an OBI system.
PMID- 28517585
TI - SU-E-J-27: Effects of Metal Artifacts of KV and MV CT Images on Structure
Delineation and Tissue Electron/Mass Density Calculation.
AB - PURPOSE: To quantitatively evaluate effects of image artifacts of hip prostheses
on the accuracy of structure delineation and tissue density calculation on kV and
MV CT images. METHODS: Five hip prostheses made of stainless steel, titanium and
cobalt chrome alloys were positioned inside a water tank and scanned respectively
on a Philips CT and a Tomotherapy Hi-Art unit. Prostheses were positioned to
mimic single and bilateral implantations. Rods of tissue materials of lung, water
and bone were placed at locations next and distal to metal implants near femoral
head, neck and stem of prostheses. kV and MV CT scans were repeated for each
placement. On CT images, cross-sectional outlines of metal implants and tissue
rods were delineated. Densities of rod materials were determined and compared to
the true values. RESULTS: Metal artifacts were severe on kV CTs and minimal on MV
CTs. Cross-sectional outlines of metal implants and tissue rods on kV CTs were
severely distorted by artifacts while those on MV CTs remained clearly
identifiable. For kV CTs, deviations of measured tissue density from true value
were up to 51.3%, 30.6% and 40.9% respectively for lung, bone and solid water.
The magnitude of deviation was generally larger at locations closer to metal
implants and greater with bilateral implants than single implant. For MV CTs,
deviations of measured density from true value were less than 6% for all three
tissue materials either with single or bilateral implants. Magnitude of deviation
appeared to be uniform and independent of locations relative to metal implants.
CONCLUSIONS: High Z metal artifacts on kV CTs can have severe impact on the
accuracy of structure delineation and tissue density calculation, while on MV
CTs, the impact is substantially less and insignificant. MV CTs should be
considered for treatment planning on patients with high Z metal implants.
PMID- 28517584
TI - SU-E-J-35: A Model for the Simulation of EPID Measurements in the BeamNRC Monte
Carlo Package.
AB - PURPOSE: The intent of this study was to create a virtual model of a simple
Electronic Portal Image Device (EPID) in the BeamNRC Monte Carlo package which
would simulate EPID measurements taken in vivo. METHODS: A typical accelerator
was created in the BeamNRC software using published 6MV spectra from Mohan, et.
al. and the basic head design of a Varian accelerator head. The particle fluence
at the level of the mylar window was output into a planar 'phase space' file. The
output of this accelerator was delivered to a phantom with a 1 mm thick slab of
water acting as the detector array using the DosXYZ package. Additionally, the
fluence from the same geometry was computed at the level of the virtualEPID
(vEPID). The simulations were run for 2*2, 5*5, 10*10, 20*20, and 25*25 field
sizes, as well as a simple IMRT field. The results of the open field simulations
were then used for the parameterization of a deconvolution kernel using the form
described by Renner, et. al. RESULTS: The simulations were run with sufficient
histories to produce a 1% uncertainty in the resulting fluence and dose matrices
in the high dose/fluence region of the output. Additional software was created to
convert 'phase space' files to fluence in the same grid as the vEPID. A final
software package was written to iteratively determine the exponential fitting
parameters described in Ritter, et. al. to deconvolve the detector function from
the fluence measurements. CONCLUSIONS: The system will allow one to simulate both
EPID measurements, as well as remove the detector function from vEPIDsimulations
for further use in fluence studies using BeamNRC. This will allow one to simulate
a system for in vivo patient measurements using an EPID to study without the need
for time on a medical accelerator, and without contributing additional radiation
fatigue to the EPID device.
PMID- 28517586
TI - SU-E-J-36: A Flexible Integration of Key Technologies in Image-Guided
Radiotherapy for Accurate Radiotherapy System (ARTS-IGRT).
AB - PURPOSE: Image-guided radiotherapy (IGRT) is becoming increasingly important in
the planning and delivery of radiotherapy. With the aim of implementing the key
technologies in a flexible and integrated way in IGRT for accurate radiotherapy
system (ARTS), a prototype system named as ARTS-IGRT was designed and completed
to apply main principles in image-guided radiotherapy. METHODS: The basic
workflow of the ARTS-IGRT software was completed with five functional modules
including management of patient information, X-ray image acquisition, 2D/2D
anatomy match, 2D/3D match as well as marker-based match. For 2D/2D match, an
image registration method was proposed based on maximization of mutual
information with multi-resolution and regions of interest. For the 2D/3D
registration, optimizations have been employed to improve the existing digitally
reconstructed radiography generation algorithm based on ray-casting, and also an
image registration method based on implanted markers with different numbers was
adopted for 3D/3D match. In additional, the kV X-Ray imaging on rail device was
finished for a better internal anatomy image checking at any angle. Together with
an infrared device, a positioning and tracking system was developed as well for
accurate patient setup and motion monitoring during each treatment. RESULTS: A
lot of tests were carried out based on the head phantom to testify the
availability of the improved algorithms. Compared with a set of controlled
experiments adopted on the released commercial IGRT platform in the hospital, the
functions of both software and hardware were testified comprehensively. The
results showed a validity verification of ARTS-IGRT. CONCLUSIONS: The accuracy
and efficiency of ARTS-IGRT on both software and hardware proved to be valid. And
also with a flexible and user-friendly interface it can meet the principles of
clinical radiotherapy practice. Supported by the Natural Science Foundation of
Anhui Province (11040606Q55) and the National Natural Science Foundation of China
(30900386).
PMID- 28517588
TI - SU-E-J-47: Evaluation of the Mismatches Between DRR's and Port Films for IMRT
Fields.
AB - PURPOSE: To quantify the frequency and magnitude of mismatches between the MLC
shape on the DRR created by the Pinnacle planning system and the corresponding
port film MLC shape generated by the Mosaiq record-and-verify system for IMRT
fields. METHODS: A retrospective review was made of the most recent 60 patients
to receive IMRT at our clinic. The MLC shape on the DRR created by the Philips
Pinnacle planning system for each treatment field was reviewed (573 fields total)
and compared with the MLC shape of the port film image, which was generated by
the Mosaiq treatment planning system. RESULTS: Of the 60 patients studied, 20 had
at least one leaf mismatched between the MLC shape on the DRR and port film (142
of the 573 fields). Of the affected cases, on average 59% of the fields had a
mismatch. The affected fields had an average of 6.7 leaves mismatched with a mean
discrepancy of 27mm. The average maximum discrepancy for each affected patient
was 69mm. Discrepancies were most common for head and neck cancers. CONCLUSIONS:
The MLC shape Mosaiq generates for the port film is the CIAO, or Complete
Irradiated Area Outline, which is the area that is actually treated. The Pinnacle
DRR displays the maximum leafmotion, which can be different for larger fields in
which the MLC leaves abut within the collimator jaw opening. The discrepancy can
create substantially different MLC shapes. The problem can be solved by not
filming the MLC shape and only using the films for isocenter placement; however,
displaying the area receiving treatment can be a useful safety check, possibly
preventing a treatment error. The persons assessing the films must be aware of
this issue and evaluate the films carefully.
PMID- 28517587
TI - SU-E-J-09: Performance Optimization of Thick, Segmented Scintillators for
Radiotherapy Imaging.
AB - PURPOSE: Thick segmented scintillators, incorporating a 2-dimensional matrix of
optically-isolated scintillator elements, have shown considerable potential for
improving the performance of megavoltage active matrix, flat-panel imagers (MV
AMFPIs). While over a factor of 20 improvement in DQE at zero spatial-frequency
has been demonstrated for prototypes incorporating CsI(Tl) and BGO scintillators,
less-than-optimal element-to-element alignment (misalignment) as well as mis
registration to the underlying AMFPI array pixels can result in spatial
resolution loss, reducing DQE improvement at higher spatial frequencies. In this
presentation, a method to restore spatial resolution and DQE, based on the use of
a high resolution AMFPI array along with special binning techniques, is
investigated. METHODS: The effect of misalignment and mis-registration of
segmented scintillators on imaging performance was investigated theoretically and
empirically through determination of the modulation transfer function (MTF) and
DQE, as well as through realization of reconstructed images of a phantom in a
cone-beam CT geometry. The empirical investigation, which was conducted using a 6
MV photon beam, employed a prototype BGO segmented scintillator consisting of
120*60 elements separated by 50 MUm-thick septal walls and an element-to-element
pitch of 1016 MUm. The scintillator was coupled to a higher resolution 127-MUm
pitch AMFPI array. RESULTS: Misalignment and mis-registration result in
significant degradation of spatial resolution, leading to DQE reduction at non
zero spatial frequencies. While mis-registration for a well-aligned scintillator
can be overcome through 8*8 binning of the array pixels to match the scintillator
elements, any misalignment will affect such binning and lead to spatial
resolution loss. However, the use of 'selective' binning, consisting of the
selection of those pixels corresponding to the interior locations of each
element, improves resolution while preserving DQE. CONCLUSIONS: The use of high
resolution AMFPI arrays combined with selective binning allows prototype AMFPIs
incorporating thick, segmented scintillators to achieve imager performance
limited only by scintillator performance. Work Supported by NIH grant R01
CA051397.
PMID- 28517589
TI - SU-E-J-20: Evaluation of Image Qualities and Registration of Varian KV-CBCT
Images Reconstructed from the Reduced Number of Projections.
AB - PURPOSE: To quantitatively investigate image qualities of the kilo-voltage cone
beam CT images reconstructed with reduced number of projections on the Varian OBI
system. Evaluate the registration accuracy using those CBCT images against the
reference CT images. METHODS: CBCT images were obtained from Varian OBI system
using standard dose head, pelvis and pelvis spotlight modes. CBCT reconstructions
were performed with full, 1/2, 1/4, 1/6 and 1/8 of the full set of projections.
Catphan(r) 504 phantom was used to evaluate high-contrast spatial resolution, low
contrast visibility and uniformity. Rando phantom was imaged for rigid
registration study. Rando was set up on the linac couch deliberately shifted by
1cm in vertical, lateral, and longitudinal (no rotational) directions from the
reference position. Automatch followed by manual adjustment was conducted 5 times
to obtain the average shifts. The same method of analysis in the Rando study was
used for the clinical registration study. One patient was imaged with pelvis mode
and two patients were imaged with pelvis spotlight mode. RESULTS: The Catphan
study indicates that high-contrast spatial resolution and uniformity are
virtually not affected by the lowest projection-number (1/8) reconstruction
scheme. However low-contrast visibility degrades when the projection number used
for reconstruction is as low as 1/6. Rando study shows that registration accuracy
can be achieved with images reconstructed with 1/6 of the full set of
projections. Patient study shows similar results exhibited in Rando study.
However, noisy images and streak artifacts are more pronounced with fewer
projections (approximate 1/6), which decreases viewer's ability to visualize soft
tissues in pelvic sites. CONCLUSIONS: This study shows that KV-CBCT reconstructed
with fewer number (approximately as low as 1/6) of regular projections can be
used for registration against the reference CT. Although the results are
encouraging, more clinical cases should be evaluated in the future. None.
PMID- 28517590
TI - SU-E-J-58: Patient-Specific Biomechanical Head and Neck Models for Interfraction
Dose Accumulation.
AB - PURPOSE: In this abstract, we discuss a biomechanical head and neck model that
will be able to represent patient setup variations as well as physiologic changes
and subsequently enable dose calculations on the deformed anatomy. METHODS: We
selected Multi Pose MRI as the imaging modality to aid in model development and
validation. The MRI data allowed us to build a biomechanically predictive model
that will enable accurate estimation of tumor position when seeded with CT data
alone. The soft tissue contrast and lack of ionizing radiation when using MRI
enabled us to acquire extensive imaging datasets with a suitable variety of head
pose variations. These poses were selected to encompass the clinical positioning
variations so that the resulting model will accurately reflect internal organ
motion and deformation. All images were acquired using an 8-channel, 1.5T
research MRI system in radiology. The imaging volume extended from about T3(upper
thoracic vertebrae) to the top of the head, thereby covering the entire head and
neck. Model components included: muscles, skeletal bones, lymph nodes, fat
tissues, and organs such as salivary glands, tendons, andligaments. At first, one
MRI image dataset was selected as the reference image. The biometric properties
(length, volume, mass, shape), hinge constraints of the bones, and the
biomechanical properties of each of the anatomies were estimated using MRIs
acquired at different head and neck poses. RESULTS: The model's ability to
represent different head and neck postures can be illustrated by observing the
internal tissue deformations andthe model's ability to represent different
postures. CONCLUSIONS: Results show that the biomechanical model was able to
simulate different poses that may be exhibited during interfraction patient setup
variations and intrafraction patient motion. Future work would focus on
integrating dose calculations on the deforming model and validating the model
deformations.
PMID- 28517591
TI - SU-E-J-31: Direct Point Dose Verification Using IGRT for Actual Beam Delivery.
AB - PURPOSE: In radiation therapy, treatment planning for patients is performed using
pre-acquired CT images. However, many patients with head-and-neck (H&N) cancer
have tumor shrinkage and/or weight loss during their treatment course. Daily
positional error of patients also causes unexpected deviations from the planning.
Thus, it is essential to evaluate actual delivered dose for accurate clinical
dosimetric consequence. In this study, actual delivered dose for an H&N site was
determined by direct point dose measurement with metal-oxide-semiconductor field
effect transistor (MOSFET) detectors using IGRT procedure. We experimentally
evaluated usefulness of the IGRT procedure for accurate irradiations. METHODS:
Treatment processes from planning to beam delivery were performed for an H&N site
of an anthropomorphic phantom. The MOSFET detectors were fixed inside the phantom
in advance. Then, the anthropomorphic phantom was immobilized with a mould and
mask and scanned by simulation-CT. Beam irradiation condition was field size of
12 cm * 12 cm, gantry angle of 0 degrees , 90 degrees and 330 degrees , and 6 MV
X-ray. Dose distribution was calculated with superposition algorithm with 2 mm
calculation grid. Before the dose measurement, the anthropomorphic phantom was
positioned using a localization system of mega-voltage cone-beam CT (MVCBCT). The
MOSFET detectors were exposed five times according to a treatment plan. Measured
doses with the MOSFET detectors were compared with calculated doses. RESULTS:
Using the MVCBCT, the set-up of the anthropomorphic phantom was achieved within 1
mm in all directions of anterior/posterior, left/right, and superior/inferior.
The calculated doses agreed well to the measured doses within +/-3% even in
evaluated region with high dose gradient. CONCLUSIONS: The actual delivered dose
for an H&N site of an anthropomorphic phantom was evaluated experimentally with
the MOSFET detectors. The IGRT procedure was useful for accurate irradiations.
PMID- 28517592
TI - SU-E-J-03: Positioning Errors of Metal Localization Devices with Motion Artifacts
on KV and MV Cone Beam CT.
AB - PURPOSE: To investigate motion artifacts of kV CBCT and MV CBCT images on metal
localization devices for image guided radiation therapy. METHODS: 8 MU pelvis
CBCT template for Siemens Artiste MVision and Pelvis template for Varian IX on
board Exact Arms kV were used to acquire CBCT images in this study. Images from
both CBCT modalities were compared in CNRs, metal landmark absolute positions,
and image volume distortion on three different planes of view. The images were
taken on a breathing-simulated thoracic phantom in which several typical metal
localization devices were implanted, including clips and wires for breast
patients, gold seeds for prostate patients, and BBs as skin marks. To magnify the
artifacts, a 4cm diameter metal ball was also implanted in the thoracic phantom
to mimic the metal artifacts. The amplitude of the sinusoidal breathing was 1cm,
and the period varies from 2sec, 4sec to 8sec. RESULTS: For MV CBCT, the CNR at
4sec breathing cycle with 1cm breathing amplitude was 5.0, 3.4 and 4.6 for clips,
gold seeds and BBs, respectively while it was 1.5, 2.0 and 1.6 for kV CBCT. On
the images, kV CBCT showed symmetric streaking artifacts both in the transverse
and longitudinal directions relative to the motion direction. kV CBCT images
predicted 89% of the expected volume, while MV CBCT images predicted 95% of the
expected volume. Simulated soft tissue observed in MVCT cannot be detected in
kVCT. CONCLUSIONS: MV CBCT images showed better volume prediction, less streaking
effects and better CNRs of a moving metal target, i.e. clips, BBs, gold seeds and
metal balls than kV CBCT images. MV CBCT was more advantageous compared to kV
CBCT with less motion artifacts for metal localization devices.
PMID- 28517593
TI - SU-E-J-40: Lung Lesion Tracking Using Fixed-Spaced Non-Migrating Fiducial Markers
in Robotic Radiosurgery.
AB - PURPOSE: With lung lesion treatment being a major indication of the use of the
CyberKnife (CK) robotic radiosurgery system (Accuray Inc, Sunnyvale, CA), the
ability for the CK's stereoscopic kV imaging system to accurately track implanted
fiducial markers becomes vital in the accurate delivery of therapeutic radiation.
This study examines a novel fixed-space fiducial marker delivery system which is
capable of delivering two VISICOIL (IBA Dosimetry America, Memphis, TN) non
migrating fiducial markers simultaneously at a fixed spacing through a single 20
gauge needle. More specifically, presented herein is a preliminary study which
tests the CK'streatment localization system's (TLS) ability to track markers of
varying size and spacing, comparing subsequent stereoscopic kV imaging to DRR's
generated during the planning stages. METHODS: Three markers were placed in an
XLT Lung Phantom (CIRS Inc, Norfolk, VA); two markers inserted along a diagonal
line in a coronal plane, separated by biocompatible spacersof varying size, and a
common third marker being placed in a non-varyinglocation in a coronal plane
anterior to the marker pair. This third marker allows the calculation of
rotational and translation corrections. Differentcombinations were scanned,
planned, and simulated; 3.5mm- and 5.0mm- long markers, each 5mm in diameter,
were separated by 15mm, 17mm, and 20mm spacers. RESULTS: The TLS system was able
to track each of the aforementioned configurations with standard lung imaging
parameters.Longer markers were not included in the study since earlier studies
showed that without the natural deformation that would occur upon implantation,
the length would induce false tracking. CONCLUSIONS: This is a necessary
firststep in determining the minimum spacing with which the CK's TLS can track, a
study which can now proceed with the use of phantom treatments elivered to
orthogonally-overlapping radiochromic film, bisecting a tumor volume which is
implanted with this fiducial marker system. Research supported in-part by IBA
Dosimetry America.
PMID- 28517594
TI - SU-E-J-13: A Study to Establish the Effect of CBCT Image Rotational Displacement
on IGRT and ART Lung SBRT Treatments.
AB - PURPOSE: To determine whether the accuracy of CBCT based IGRT and ART lung SBRT
treatments may require extra quality assurance (QA) steps. METHODS: During CBCT
Rando phantom acquisition we detected an unexpected ~2 degrees image rotation
when comparing the CW and CCW acquired scans. Misregistered angular coordinates
may Result in a rotated reconstructed image and the target localization may lead
to an under- or over-dosage of the target volume (TV) and organs at risk (OARs).
The effect of image rotation on CBCT-guided lung SBRT was retrospectively
examined in a group of six patients treated at our institution. Patient CT sets
were rotated by 1,2, and 3 degrees . Treatment plans were recalculated using
these rotated images to examine changes of dose-volume histogram indicators for
IGRT and ART guided treatments. C++ simulations were run to evaluate the effect
of CBCT image rotation. RESULTS: We determined through mathematical analysis that
the dose coverage of the TV is dependent on its shape, location and orientation
relative to isocenter. Dosimetric evaluation of lung SBRT patients showed that
even for 1< N2 <3 degrees , changes in D95 to the PTV were from 2.3 +/- 2.1 to
11.5 +/- 3.9% for IGRT and from 8.5 +/- 8.4 to 16.6 +/- 8.0% for ART. Significant
changes were also detected at critical structure level. CONCLUSIONS: When IGRT
and ART are employed for lung SBRT treatments, significant dosimetric changes may
Result from the rotation of CBCT image data sets. The extent of alterations in
dose indicators depends on both the shape of the TV and its relative location to
isocenter. Based on our results, angular alignment of CBCT to <1 degrees is
essential in maintaining accurate dose delivery of IGRT and ART based lung SBRT
treatments.
PMID- 28517595
TI - SU-E-J-51: Interfractional Trend Analysis of Dose Discrepancies Based on 2D
Portal Dosimetry.
AB - PURPOSE: During a radiotherapy treatment course the dose delivery can be
influenced by a number of factors, e.g. anatomical changes over time. Thiscan
Result in discrepancies between planned and delivered dose. The electronic portal
imaging device has been demonstrated to be valuable fortransit dosimetry
verification. The aim of this study is to investigate theinformation that can be
derived from 2D transit portal dosimetry by examining interfractional dose
changes over a treatment course. METHODS AND MATERIALS: To create a trend
overview of the interfractional changes intransit dose, the predicted portal dose
for the different beams is compared to a measured portal dose using a ?
EVALUATION: For each beam of the delivered fraction information is extracted from
the ? images to differentiatesystematic from random dose delivery errors. From
the systematic dose errors of a fraction for different projected contours,
derived from the treatment planning contours several metrics are extracted like
percentage pixels with ? exceeding unity. Finally the extracted metrics from each
contour and beam are weighted with beam weight and the average andstandard
deviation are calculated, resulting in a fraction Result. For this study, we
analyzed 6 lung cancer patients and 20 prostate cancer patients. RESULTS: In some
prostate cases the rectal filling was causing the dose delivery problems. For the
lung cancer patients, anatomy changes from the diminishing atelectasis caused a
transit dose difference and adaptations to the plan were applied. CONCLUSION: We
have shown that from interfractional trend overview valuable information can be
derived. However, to use this for adaptive radiotherapy, 2D transit dose
differences with this methodshould be correlated with the 3D delivered dose, to
define decision criteria.By optimizing these decision criteria it should be
possible to prevent eitherover or under dosage of the tumor or OARs.
PMID- 28517596
TI - SU-E-J-24: Image-Guidance Using Cone-Beam CT for Stereotactic Body Radiotherapy
(SBRT) of Lung Cancer Patients: Bony Alignment or Soft Tissue Alignment?
AB - PURPOSE: To assess the reliability of soft tissue alignment by comparing pre- and
post-treatment cone-beam CT (CBCT) for image guidance in stereotactic body
radiotherapy (SBRT) of lung cancers. METHODS: Our lung SBRT procedures require
all patients undergo 4D CT scan in order to obtain patient-specific target motion
information through reconstructed 4D data using the maximum-intensity projection
(MIP) algorithm. The internal target volume (ITV) was outlined directly from the
MIP images and a 3-5 mm margin expansion was then applied to the ITV to create
the PTV. Conformal treatment planning was performed on the helical images, to
which the MIP images were fused. Prior to each treatment, CBCT was used for image
guidance by comparing with the simulation CT and for patient relocalization based
on the bony anatomy. Any displacement of the patient bony structure would be
considered as setup errors and would be corrected by couch shifts. Theoretically,
as the PTV definition included target internal motion, no further shifts other
than setup corrections should be made. However, it is our practice to have
treating physicians further check target localization within the PTV. Whenever
the shifts based on the soft-tissue alignment (that is, target alignment)
exceeded a certain value (e.g. 5 mm), a post-treatment CBCT was carried out to
ensure that the tissue alignment is reliable by comparing between pre- and post
treatment CBCT. RESULTS: Pre- and post-CBCT has been performed for 7 patients so
far who had shifts beyond 5 mm despite bony alignment. For all patients, post
CBCT confirmed that the visualized target position was kept in the same position
as before treatment after adjusting for soft-tissue alignment. CONCLUSIONS: For
the patient population studied, it is shown that soft-tissue alignment is
necessary and reliable in the lung SBRT for individual cases.
PMID- 28517597
TI - SU-E-J-34: Influence of Prone versus Supine Patient Position on Localization with
Image Guided Radiotherapy of Prostate Cancer.
AB - PURPOSE: To retrospectively assess the influence of prone versus supine patient
position on setup shifts and target margins for image guided radiotherapy (IGRT)
of prostate cancer. METHODS: Ninety prostate cancer patients were treated at our
institution between September 2006 and June2011 with IGRT utilizing daily
megavoltage cone beam; 52 patients were prone receiving 1577 fractions and 38
supine receiving 1035 fractions. Patients were setup to skin tattoos, imaged with
megavoltage cone beam, then moved to treatment position by the alignment of three
intraprostatic fiducials with lateral, longitudinal, and vertical shifts. The
magnitude of the daily shift is root sum of squares of the translations. RESULTS:
Patients positioned prone had a mean daily shift magnitude 1.4 mm greater than
supine: 7.5 +/- 4.0 mm vs. 6.1 +/- 2.9 mm (p ≪ 0.001). The mean magnitude of
the daily shift for prone vs. supine respectively were 3.7 +/- 3.1 mm vs. 2.6 +/-
2.3 mm laterally, 3.5 +/- 3.0 mm vs. 3.3 +/- 2.6 mm longitudinally, and 3.9 +/-
3.5 mm vs. 3.1 +/- 2.4 mm vertically. The percentage of daily shifts within our
intuition's planning target volume (PTV) margin (7 mm posterior and 10 mm for all
other directions) for prone vs. supine respectively were 97.3% vs. 99.5%
laterally, 97.1% vs. 98.2% longitudinally, and 93.1% vs. 96.8% vertically.
CONCLUSION: When prostate cancer patients were setup for IGRT utilizing daily
megavoltage cone beam, the daily shifts from the skin tattoos to intraprostatic
fiducials were greater on average if positioned prone vs.supine. Without IGRT,
part of the prostate would be outside of the PTV for more treatments when
positioned prone rather than supine.
PMID- 28517598
TI - SU-E-J-07: Image Guided Radiotherapy for Prostate Cancer: To Shift Or to Re-Plan?
AB - PURPOSE: Advanced imaging techniques have been developed to facilitate patient
setup and target localization for advanced prostate radiotherapy. These
techniques work well for translational, interfractional organ motion but may
Result in poor target coverage for some cases where the effects of rotational
motion and organ deformation are not corrected. This work investigates the
feasibility of the use of 3D dose distributions to match the target volume to
improve target coverage and critical structure sparing. METHODS: Fifteen
previously treated prostate patients were selected for this retrospective study.
Siemens CT-on-rails scans were performed before and after the IMRT treatment
weekly. Ninety-eight post-treatment CT-on-rails scans were used to reconstruct
the dose distributions. The isodose distributions and DVH were compared with
those of the original plans. Target localization was also performed using the
prescription isodose surface from the original plan to match the target volume
and a new isocenter shift was applied in the dose reconstruction, which was
evaluated against the original plans and the reconstructed dose distributions
using the standard contour-based target-localization technique. RESULTS: The
results show that for contour/anatomy matching, 7.1% of the 98 treatment
fractions exhibit poor target coverage (Dmin<65Gy). For the rectum, 27.6%
fractions violated our rectal criterion of V65<17% and 26.5% fractions violated
the criterion of V40<35%. After the isocenter realignment based on 3D dose/target
volume matching, all the fractions delivered >65Gy to the target, and the
percentages of fractions that violated the rectal criteria (V65<17% and V40<35%)
were reduced to 14.3% and 18.4%, respectively. CONCLUSIONS: The current IGRT
procedure for isocenter alignment based on contour/anatomy matching is not ideal
due to poor soft-tissue contrast, residual translational/rotational organ motion
and organ deformation. Target localization based on 3D dose/target volume
matching provides better target dose coverage and critical structure sparing that
reduces the need for adaptive re-planning.
PMID- 28517599
TI - SU-E-J-44: Dual Energy Subtraction Imaging to Improve Tumor Visibility at Oblique
Angles.
AB - PURPOSE: To characterize the contrast improvement of simulated tumors in an
anthropomorphic phantom using Dual Energy (DE) subtraction with a clinical on
board imager (OBI) at oblique angles. METHODS: An Alderson lung/chest
anthropomorphic phantom with simulated tumors in the thoracic cavity was imaged
using a sequential DE imaging methodology. High (120kVp) and low (60kVp) planar
images were obtained in pairs every 100 in a full (3600) rotation using the OBI
(Varian Medical Systems, Palo Alto, CA). Optimal mAs settings for DE component
images were determined byvarying the x-ray exposure time, while maintaining a
constant tube current. DE images were created to best suppress the bone
overlaying the simulated tumors. Tumor visibility in DE images was quantified
using the Contrast-to-Noise Ratio (CNR). The ratio of the CNR from the DE image
relative to a single image (standard protocol) was evaluated as a function of
gantry angle. RESULTS: CNR was improved with DE imaging by an average ratio of
1.66 over all gantry angles. The greatest improvement occurred at gantry angles
where the tumor was obstructed by the ribs alone. More modest improvements were
observed where the tumor overlapped other soft tissue structures (such as the
heart) or the dense spine, on a given projection. CONCLUSIONS: This study
illustrates the feasibility of performing DE imaging at oblique gantry angles
using a clinical on-board imaging system. Incorporating DE imaging into clinical
practice may allow for verification of tumor position at oblique gantry angles,
and may facilitate the development of markerless motion tracking techniques.
Supported by a grant from Varian Medical Systems.
PMID- 28517600
TI - SU-E-J-46: Use of Brainlab-ExacTrac IGRT with Dot-Decimal Electron
Compensator(BolusECT) for Accurate Patient Positioning.
AB - PURPOSE: To Validate Brainlab-ExacTrac IGRT with Dot-Decimal electron
compensator(BolusECT) for accurate patient positioning. METHODS: Dot-Decimal
electron compensators(BolusECT) are used to achieve conformal dose distributions
and greater sparing to normal structures for cases with varying patient contours
and treated with single electron beam.Setup for such patients is difficult to
verify due to the small clearance between theelectron-cone and bolus. Hence
additional verification is needed for fast setup to avoid discomfort for the
patient. In this study we have explored theuse of Brainlab-ExacTrac IGRT system
for such setups.A Preplan isrequired to construct the BolusECT and a post-plan is
used for verifying the treatment plan. Before the patient is scanned again with
BolusECT for post-plan, tungsten BBs were drilled in the Bolus at different
depths and the holeswere filled with wax. Tungsten-BBs have high density and
avoid high cost ofgold seeds.A wax phantom and BolusECT were scanned with BBs and
a plan was generated. The plan was send to ExacTrac for DRR-generation.The Wax
phantom with BolusECT was then set slightly off centered on thetreatment couch
and the ExactTrac system was used to align the Phantom. The ExacTrac system was
also tried on two patients for accurate setup. RESULTS: The ExactTrac system
correctly identified the tungsten-BBs and aligned the phantom within +1mm. The
SSD was then verified and checked with the planned SSD.The SSD was found to be
within +0.5mm. In both patient setups the ExacTrac system gave Lateral,
Longitudinal and Vertical Shifts within +1mm and the SSD was found to be within
+0.3mm of the planned SSD. CONCLUSIONS: The BrainLab- ExacTrac IGRT system isan
excellent,fast way of aligning the BolusECT. This avoids discomfort for patients
by preventing longer setup times. Use of tungsten-BBs lowers the cost compared to
gold seeds. Phantom verification should be performed before implementing this
system for actual patient use. The SSDs must be verified after setup.
PMID- 28517602
TI - SU-E-J-57: MRI-Linac (MRL) Guided Treatment for Esophageal Cancer.
AB - For radiotherapy, oesophageal cancer is located in a difficult area. Spatial
control of the dose distribution is difficult to achieve with current CT-based
radiation techniques, as on CT, soft-tissue contrast is too low. Furthermore, the
oesophagus moves and organs at risk (e.g. lung, heart, liver, spinal cord) are in
close proximity. An 1.5 T MRI-accelerator (MRL) has sufficient soft-tissue tumour
visualization possibilities to allow for precise real-time, online, position
verification and for dose escalation without organ at riskoverdose. Our research
consists of the preparatory work for the first clinical study on the MRL for
patients with oesophageal cancer. To improve image quality and reduce the motion
artefacts, the benefit of cardiac triggering and breath holds is evaluated on
fifteen oesophageal patients. Results show the superb image quality of these MRI
sequences. The use of this high quality MRI gives the possibility for non
invasive real-time visualization andtracking of the tumour. We quantify
oesophageal tumour motion on cineMRI. The tumour is tracked on sequential mixed
T1/T2w images (acquisition time: 60s, temporal resolution: 0.5s, slice thickness:
7mm) of a single coronal and sagittal slice using a Minimum Output Sum of Squared
Error (MOSSE) adaptive correlation filter. Tumour registration within the
individual images can typically be done at a millisecond time scale. Motion of
oesophageal tumours can well be tracked and is highly variable between patients.
The greatest mobility is seen in cranio-caudal direction, with amaximum peak-to
peak amplitude of tumour movement of 24.5mm followed by the dorso-ventral and the
medio-lateral direction. Movement seems greatest in tumours located in the lower
part of the oesophagus. This study shows both the superb image quality for GTV
localisation and the possibility for on-line and real time tumour tracking. The
study opens thepossibility for tracked radiation delivery with a 1.5T MRI
accelerator. Partial funding has been obtained by Elekta and Philips.
PMID- 28517601
TI - SU-E-J-19: How Should CTV to PTV Margin Be Created - Analysis of Set-Up
Uncertainties of Different Body Parts Using Daily Image Guidance.
AB - PURPOSE: The objective for this study is to systematically evaluate how the CTV
to PTV margin should be created to compensate for setup error as afunction of
treatment site. METHODS: A total of 1757 setup MVCT images were analyzed using
the registration between the MVCT and planning KVCT images. Among them, 526
images were from patients with head and neck cancers; 342 were from thoracic
site; 447 from upper abdomen and 442 from patients treated at pelvic region. The
correction was shifts in 3 directions from setup with skin marks to final
treatment position due to volumetric image registration. Registration was based
on soft tissue anatomy when tumor was visible in both KVCT and MVCT. Otherwise,
bony landmarks were used when tumors could not be identified. RESULTS: The
anterior to posterior (A/P) direction requires the smallest correction for all
body sites. The percentage of treatment with < 3mm set-up correction in A/P
direction was 82.4%-96.0% for all disease sites. In medial to lateral direction
(M/L), that number was 51.5%-74.7%. The largest set-up correction occurred in the
superior to inferior (S/I) direction. As a function of the body site, 68.6% of
head and neck patient had <3mm shift in the S/I direction. However, that number
dropped to 41.8%a? 42.5% and 31.9% for thoracic, upper abdomen and pelvic sites
respectively. In addition, 48.0% of pelvic tumor required >5mm shift in the S/I
direction. For thoracic and abdominal tumors, there were still 34.9% and 30.7% of
the treatments where >5mm shift in the S/I direction was needed. CONCLUSIONS:
Uniform expansion margins in all directions are often used in radiation oncology
practice. Our study showed setup error was directionally dependent. Therefore,
non-uniform margin should be applied. Smaller margin can be used in A/P while
larger expansion needs to be given in the S/I direction.
PMID- 28517603
TI - SU-E-J-30: Using Shifting Planned Dose Matrix to Evaluate Daily Dose Changes for
IMRT Prostate Treatment.
AB - PURPOSE: Summation of daily DVH from KV-cone beam CT (KV-CBCT) to obtain a
composite dose volume histogram (DVH) is challenging. Directly translating the
planned dose matrix according to measured daily prostate displacements provided a
common reference frame for a composite DVH from daily DVHs. The purpose of this
study is to evaluate the shifting planned dose matrix method compared to the dose
recalculation method using daily KV-CBCT. METHODS: Six patients, who received
concurrent IMRT treatment for prostate and pelvic lymph nodes with 124 daily
CBCTs, were selected for this study. Contours for CBCT's were transferred from
the planning CT after soft tissue registration for prostate and bony registration
for pelvic lymph nodes. Using the same planning beam configurations, we re
calculated doses for these CBCTs after shifting to corrected treatment
isocenters. The planned dose matrix translation was performed by an in-house
program written in MATLAB and incorporated with Computational Environment for
Radiotherapy Research (CERR) software. The corresponding daily DVH was obtained
by shifting the planned dose matrix according to shifts of treatment iso-centers.
To compare these two methods, selected endpoint doses for tumor targets and
sensitive structures were extracted from DVHs. RESULTS: For prostate displacement
less then 1.5 cm, the dose matrix shifting method resulted in 93% and 98%
fractions within 5% differences from the recalculation method for D95 of prostate
and pelvic lymph nodes, respectively. These numbers decreased to 58% and 71% when
2% dose difference criterion was used. CONCLUSIONS: Allowing 5% daily dose
difference, shifting planned dose matrix provides effective means to evaluating
daily dose changes for concurrent IMRT treatment for prostate and pelvic lymph
nodes. The utility of this tool is to provide a common coordinate frame to obtain
composite dose distributions.
PMID- 28517604
TI - SU-E-J-39: Minimizing IGRT Imaging Exposures: KV Radiograph Vs. KV-CBCT Vs. MV
Portal Images.
AB - PURPOSE: To compare the IGRT doses from MV, kV and CBCT images. METHODS: kV
imaging systems integrated into Varian Trilogy and TrueBeam accelerators were
modeled using BEAMnrc/DOSXYZnrc Monte Carlo codes and the dose to calibration
phantoms for a variety of kV beams(kVp, bow-tie filters, etc.) were calculated.
The doses to the same phantoms and kV beams were then measured experimentally
using calibrated ion-chambers.The "calibrated" Monte Carlo kV beams were used to
calculate dose to CT images of patients. Organ doses were analyzed using DVHs.
RESULTS: The doses to the prostate are 0.015 and 2.2cGy using AP kV and MV
images; are 0.06 and 2.3cGy using lateral kV and MV images; and, are 1.7 cGy
using CBCT images. For head and neck images, the doses to the eye are 0.08 and
0.001 cGy using AP and PA kV images; are 2.3 and 1.8cGy using AP and PA MV
images; are 0.001 and 2.4cGy for lateral kV and MV images; and, are 0.2 cGy for
CBCT images. For kV radiographs, organ doses can be further reduced, by over 30%,
by using bow-tie filters. CBCT doses to the prostate are 1.6 and 0.9cGy for OBI
and TrueBeam pelvis scans; a >40% dose reduction for the same image quality. For
OBI CBCT head scans the doses to the eye and brain stem are 0.2 and 2.8cGy,
respectively. CONCLUSIONS: Due to the low penetration of kV beams,selecting beam
angles so that the sensitive organs are near the beam exit, and/or using bow-tie
filters, can substantially reduce organ doses when using kV radiographs. For
daily positioning of pediatric brain patient with a set of orthogonal kV images,
a CBCT scan, or a set of orthogonal MV images, the doses to the eyes are 0.1,
0.2, and 4.7 cGy, respectively.
PMID- 28517605
TI - SU-E-J-12: Initial Clinical Experiences in Using 4D-CBCT as Image Guidance for
Lung SBRT.
AB - PURPOSE: The authors started to use Symmetry 4D-CBCT as image guidance for lung
SBRT in August 2011. Here the authors present the initial clinical experiences
with this novel image guidance technique. METHODS: In total 118 4D-CBCT scans
have been acquired for 17 lung patients among which 15 received SBRT and the
other 2 received hypofractionated treatments. 4D-CBCT scans are acquired with
Elekta XVI 4.5 usingSymmetry, a procedure module in XVI that acquires 4D-CBCT,
registers daily images to reference 3D-CT and generates shifts for patient setup.
RESULTS: Typical thoracic 4D-CBCT scans with Symmetry take 3 minutes with a 200
degree gantry rotation. Symmetry automatically sorts images into 10 phases based
on automatic detection of diaphragm position. Then Symmetry generates two
independent intensity-based registrations, one according to a pre-defined large
volume of interest including the tumor, surrounding tissues and bony structures,
the other only according to an expanded target volume. The registrations are
obtained by registering each phase image to the reference image and averaging
across all phases in a time-weighted manner. Eventually Symmetry provides users
the freedom to pick either one of the two registrations, a compromise, or a
manual tuning. Compared to regular 3D-CBCT, 4D-CBCT enables physicians to
visually place the moving target in the center of PTV, greatly reducing the
probability of missing target due to respiratory motion, thus enables possible
reduction in PTV margin. 4D-CBCT also provides the ability to repeatedly evaluate
the quality of ITV. It is possible that ITV does not fully cover the tumor motion
due to a low quality 4D-CT simulation for a patient with difficulties in regular
breathing. CONCLUSIONS: 4D-CBCT is a superior image guidance technique for lung
SBRT treatments for its ability to visualize moving target. It provides
physicians more confidence in tumor targeting and ability to repeatedly evaluate
ITV quality during the treatment course.
PMID- 28517606
TI - SU-E-J-50: Measurement of the HVL Value for the 120keV Photon Beam of the X-Ray
Volume Imager (XVI) Using Ionization Chamber, Gafchromic Film XRQA2 and Diode.
AB - PURPOSE: The value of Half Value Layer (HVL) is essential in quantifying the
ability of an x-ray beam to penetrate the material being studied. This paper
examines the use of three different types of detectors for measuring HVL of the
120keV photon beam of the X-ray Volume Imager (XVI) cone beam CT system mounted
on the Elekta Synergy (Crawley, UK) Linac: ionization chamber, Gafchromic film
and diode. The effects of collimator diameters are presented and the chamber tip
and chamber horizontalmethods are compared to investigate the source of
variations in the measurement of HVL. METHODS: The measurements are done in free
airboth using an ionization chamber calibrated for absolute dosimetry [University
of Wisconsin Accredited Dosimetry Laboratory] and the Gafchromic film dosimeters
[XR-QA2 (International Specialty Products, Wayne, NJ)]. The beam is collimated to
the size of the detector to measure the exposed dose. The different thicknesses
of the aluminum attenuators are added to beam to measure individual doses every
time and repeated until the dose fell to below 50% of the initial unattenuated
value. Dose measurements with a semiconductor diode detector [Barracuda MPD (RTI
Electronics AB, NJ)] is also carried out. We plotted all results on a semi-log
graph to find HVL value. RESULTS: When the measurements are made using ionization
chamber with different collimator diameters we obtained 1.6% difference in HVL
values. Measurements with chamber tip and horizontal methods agree with each
other to within approximately 1.6% percentage difference. The percentage
difference of the HVL values measured using the diode and ionization chamber is
about 6.4% and that of using Gafchromic film and ionization chamber is about 8%
percent. CONCLUSIONS: Gafchromic films and diodes can be used to measure HVL
value of 120 keV photon beams. Recommendations for consistency in HVL
measurements are provided.
PMID- 28517607
TI - SU-E-J-23: Prostate Bed Motion Study Using Surgical Clips Based on Daily CBCT.
AB - PURPOSE: To study prostate-bed motion after prostatectomy using the surgical
clips as a surrogate. METHODS: On the treatment planning CT, surgical clips
within the PTV are identified and contoured. They are also identified and
contoured in each daily CBCT. The center of mass (COM) coordinates for each clip
within the native reference frame of each image set of CT and CBCT are recorded.
Each CBCT (for daily image guidance) is registered to the planning CT based on
the pelvic bony structure. The resulted 3D transformation matrix is used to
convert the clip coordinates in the CBCT to the planning CT reference frame.
Difference between the converted COM coordinates and the one in planning CT is
taken as the rigid motion of the prostate bed relative to the pelvic bony
structure during the course of radiation therapy. The motion data are then
analyzed using statistical error analysis and quantified by the commonly defined
M (average over all fractions and all patients), S (stdev of averages per
patient, the systematic motion), and s (root mean square of stdev per patient,
the random motion). Among a large pool of patients, seven patients were selected
for this retrospective study, each with 3 to 11 identifiable clips and 17 to 26
CBCT sets. The total number of clips is 44 and total daily CBCT sets 160.
RESULTS: In the (right-left, anterio-posterior, foot-head) directions, the M
values are (0.2 mm, 0.4 mm, -0.6 mm), S (0.2, 2.5, 3.2), and s (1.7, 2.6, 2.1).
CONCLUSIONS: Relative to the bony pelvic structure, the prostate bed motion
characteristics are similar to that of intact prostate, as summarized in Table 2
of Rasch et al 2005 ('Target Definition in Prostate, Head, and Neck.' Semin
Radiat Oncol 15:136-145).
PMID- 28517608
TI - SU-E-J-61: Multi-Criteria Optimization for IGRT Decision Processes.
AB - PURPOSE: To develop a multi-criteria optimization framework for image guided
radiotherapy decision processes. METHODS: An algorithm is proposed for a multi
criteria framework for the purpose of patient setup verification decision
processes. Optimal patient setup shifts and rotations are not always
straightforward, particularly for deformable or moving targets of the spine,
abdomen, thorax, breast, head and neck and limbs that change as a Result of
treatment. The algorithm relies upon dosimetric constraints and objectives to aid
in the patient setup and plan delivery such that the patient is positioned or the
plan is optimized to maximize tumor dose coverage and minimize dose to organs at
risk while allowing for daily clinical changes. A simple 1D model, a lung lesion
are presented and a spine lesion. RESULTS: The algorithm delivers a multi
criteria optimization framework allowing for clinical decisions to accommodate
patient target variation which make setup decisions less straightforward. With
dosimetric considerations, optimal patient positions and plan parameters can be
derived. CONCLUSIONS: A multi-criteria framework is demonstrated to aid in the
patient setup and determine the most appropriate daily position considering
dosimetric goals. Future implementations include optimizations relying upon
multiple plans, field parameters, and other dose metrics (TCP, NTCP, EUD, etc).
PMID- 28517609
TI - SU-E-J-06: A Time Dependence Analysis of CBCT Image Quality and Mechanical
Stability.
AB - PURPOSE: To quantify the change, if any, in flexmap correction factors and image
quality with the XVI system over a course of several years and from these
results, assess their clinical impact. METHODS: Flexmap, a calibration procedure
which corrects for imperfect gantry rotation for cone-beam CT reconstruction, and
image quality tests were performed on three Elekta Synergy linacs equipped with
XVI. Data was collected per month over three years. U and V values, corresponding
to lateral and longitudinal shifts respectively, were acquired through the XVI
software. Image quality parameters were obtained through CT imaging of the
Catphan 500(r). For each reconstruction, pixel values for low density
polyethylene (LDPE) and polystyrene materials were recorded. RESULTS: For all
three linacs, analysis of the flexmap showed a significant change in the U factor
for both month-to-month comparisons and comparisons between machines. The V
correction factor exhibited a small variation month to month, and showed a
slight, gradual increase over time (0.2 +/-0.08 mm). Image quality analysis
showed a near consistent decrease (5-10%) in LDPE and polystyrene. Despite this
decrease in pixel values, the ratio of the two pixel values remained constant,
thus a similar decreasing trend in contrast was not observed. CONCLUSIONS:
Analysis of monthly flexmap calibration showed the general monthly change in
correction shifts and their general trend over several years. For image quality,
our research exhibited roughly 0.5% per month decrease in pixel values of the
Catphan(r). Our results imply that CBCT images obtained from XVI are not
appropriate for treatment planning and despite the decrease in panel response
over time, image quality with respect to contrast will remain within acceptable
clinical standards. Future studies may be carried out to assess any correlation
between image quality and XVI source strength.
PMID- 28517610
TI - SU-E-J-43: Autotuning Imaging Parameters in X-Ray Fluoroscopic Tracking for Dose
Savings.
AB - PURPOSE: In fluoroscopy-guided clinical procedures that involve tracking objects
over long treatment times, there is a need for reducing the amount of imaging
dose delivered to the patient and the operating staff. In this study, we
introduce a feedback metric to minimize tube current while maintaining a
targeting precision threshold. METHOD AND MATERIALS: An acrylic sphere (1.6mm in
diameter) was imaged at tube currents ranging from 0.5 mA to 0.9mA (1s) at a
fixed energy of 50kVp. The images were acquired on a Varian Paxscan 4030A
(2048*1536 pixels, 1100 mm source-to-axis distance, 1570 mm source-to-detector
distance). A state feedback metric (tr(C)) based on the current object position
was computed and plotted as afunction of the tube current. Next, the sphere was
tracked using a particle filter with a bowtie filter (4.3-764mm thickness, Al) in
the background. The tr(C) was used a by a PID controller to modulate the tube
current in order to maintain a specified precision as the sphere traversed
regions of varying thickness corresponding to the bowtie filter. RESULT:
Comparison of thefeedback framework with a similar system employing fixed
exposurereveals a dose savings of up to 43% when using an operating uncertainty
of 194 mm2 . CONCLUSION: This work presents a relation between tr(C) and thetube
current which can be leveraged to reduce imaging dose to patients and staff.
PMID- 28517611
TI - SU-E-J-16: Prostate Bed Motion during Post-Prostatectomy Radiotherapy.
AB - PURPOSE: To report the inter-fractional prostate bed motion (PBM) during post
prostatectomy radiotherapy using cone-beam CT (CBCT). The correlations between
PBM, anterior rectal wall and posterior bladder wall shifts were also
investigated. METHODS: Seventy CBCT and 8 planning CT scans from 8 patients
treated with prostate bed radiotherapy were retrospectively analyzed. For each
CBCT-CT pair, two rigid image registrations were performed: one based on surgical
clips and the other based on pelvic bony anatomy. Each registration gives a
displacement vector. The difference between the two registration displacements
represents the PBM. In addition, rectum/bladder contours on CT and CBCT scans
were compared to identify the organ wall motion. Shifts of the anterior rectal
wall and posterior bladder wall were assessed by averaging the slice-by-slice
distances between contours on two image sets, measured along an anterior
posterior line passing through the symphysis pubis. RESULTS: The prostate bed
motion in the left-right (LR), anterior-posterior (AP) and superior-inferior (SI)
directions was (0.1+/-0.9)mm, (0.9+/-1.6)mm, and (-0.4+/-1.9)mm, respectively.
The derived PTV-CTV margin for LR, AP and SI motion was 3mm, 5mm, and 6mm,
respectively. Pearson's correlation coefficients between PBM and anterior rectal
wall (whole length) shifts, PBM and the cranial half of anterior rectal wall
shifts, and PBM and posterior bladder wall shifts, were 0.43, 0.47, and 0.67,
respectively. CONCLUSIONS: The magnitude of PBM relative to pelvic bony anatomy
in all three directions was small. The correlation between average anterior
rectal wall shifts and PBM was weak-to-moderate, which may be due to rectum
contouring inconsistency. Possible sources for this inconsistency include: non
uniform rectal wall motion through its length, low CBCT image contrast, and
artifacts due to filling. Significant correlation between average posterior
bladder wall shifts and PBM suggests bladder wall motion may also be a suitable
surrogate for PBM in the AP direction.
PMID- 28517612
TI - SU-E-J-54: Bone Detection in MR Images and Absorbed Dose in a Material Behind
Bones in Radiotherapy.
AB - PURPOSE: To determine whether bones could be localized accurately by using MR
images only in radiotherapy treatment planning. Furthermore, to measure absorbed
dose in a material behind different parts of the bone, and to evaluate dose
calculation error in a pseudo-CT image by assuming a single electron density for
the bones. METHODS: A dedicated phantom was constructed using fresh deer bones
and gelatine. The accuracy of the bone edge location and the bone diameter in MR
images were evaluated by comparing those in the images with the actual measures.
The absorbed dose behind the bones was measured by a matrix detector at 6 and 15
MV. Thedose calculation error in the bulk density pseudo-CT image was quantified
by comparing the calculation results with those obtained in a standard CT image
by superposition and Monte Carlo algorithms (TPSs: Xio 4.60 and Monaco 3.00,
Elekta CMS Software). RESULTS: The examination of bone position revealed that the
bones can be localized within a 1-mm-pixel-size in the MR images. The measured
dose behind less than 2.5-cm-thick femur indicated that the absorbed dose behind
the middle part of the bone is approximately one percentage unit (6 MV: 1.3%, 15
MV: 0.9%) smallerthan that of the physically narrower bone edge. The calculations
illustrated that the bulk density pseudo-CT image used causes errors up to nearly
2% to the dose behind the middle part, but also, the edge of the femur.
CONCLUSIONS: This research ascertains that the bone localization is not a
restrictive issue for radiotherapy treatment planning by using MR imageonly. The
work indicates also that the decrease in absorbed dose is not necessarily
dependent on the diameter of the bone. Future research shouldinvestigate the
generation of more complex pseudo-CT images and the dosecalculations by using
these. Supported by Elekta.
PMID- 28517614
TI - SU-E-I-113: Alignment and Assembly of Small Field of View Pre-Clinical Images
Taken with a Micro-Solid State X-Ray Imaging Detector.
AB - PURPOSE: We have developed a Micro-Solid State X-ray Imaging Intensifier
(MUSSXII) detector with an electron multiplying (EM)CCD chip which allows for an
ultra-high pixel resolution of 8 * 8 microns. However, the EMCCD chip area of
1004 * 1002 pixels results in an 8.032 * 8.016 mm imaging area and restricts the
ability of the user to orient and properly image larger pre-clinical objects such
as rat-kidney-vasculature casts. We propose a method to align and assemble images
of such larger structures while preserving the ultra-high spatial resolution of
the MUSSXII. METHODS: An imaging platform of negligible attenuation was attached
to a stepper motor giving the platform free movement in the plane normal to the
fluoroscopic x-ray beam. By alternating the detector's image acquisition and the
stepper movement, many adjacent overlapping views of the object are acquired. The
user then identifies the two pixel coordinates in adjacent images which represent
the same point in space. A custom Matlab computer code uses the pixel coordinates
to aggregate and average the input images which results in a larger field of view
consisting of many ultra-high resolution images. RESULTS: The images were able to
be successfully combined to form a large image while preserving the ultra-high
resolution of the detector. In experimental tests, multiple portions of a
mammography test object were imaged and virtually no spatial resolution
degradation was found in the combined image. Additionally, when imaging a resin
cast of rat-kidney-vasculature, vessels of less than 50 MUm could be viewed in
the combined image. CONCLUSIONS: The setup and method were found to preserve the
ultra-high resolution inherent to the MUSSXII while allowing pre-clinical imaging
of objects larger than the detector's field of view. The large field of view was
effective in orienting the user towards specific areas of interest in the objects
imaged. Supported in part by: NIH Grants R01-EB008425, R01-EB002873, and an
equipment grant from Toshiba Medical Systems Corp.
PMID- 28517615
TI - SU-E-I-84: A Novel Approach for the Attenuation Correction of PET Data in PET/MR
Systems.
AB - PURPOSE: To evaluate the use of non-attenuated PET images (PET-NAC) as a means
for the attenuation correction (AC) of PET images in PET/MR systems. METHODS: A 3
step iterative segmentation process is proposed. The first step is used to
segment the body contour from the NAC PET images using an active contour
algorithm (Kass et al., Int J Comput Vision, 321-331 (1988)). The second step was
to segment the lung region from the resultant image using an optimal thresholding
approach (Xu et al., IEEE T Nucl Sci, 43, 331-336 (1996)). The purpose of the
third step was to delineate parts of the heart and liver from the lung contour
using a region growing approach since these parts were unavoidably included in
the lung contour of the second step. Finally the attenuation coefficients of the
bed were included based on CT images to eliminate the impact of the couch on the
accuracy of AC. The final attenuation map was then used to AC the raw PET data
and Result in a final PET image (PET-IAC). To assess the proposed segmentation
approach, a phantom and six patients were scanned on a GE Discovery-RX PET/CT
scanner. PET-IAC was then generated from PET- NAC using the proposed approach and
compared to those of CT-AC PET (PET-CTAC). Visual inspection and SUV measurements
between PET-IAC and the PET-CTAC for phantom and patient studies were performed
to assess the accuracy of image quantification. RESULTS: Visual inspection showed
a small difference between the PET-IAC and PET-CTAC. PET-IAC tumor SUVs were on
average equal to 103+/-9% compared to the SUVs from the PET-CTAC in the phantom
study, and 110+/-7% in the patient studies. CONCLUSIONS: Preliminary results
suggest that PET-NAC for the AC of PET images is feasible in the clinic. Such an
approach can potentially be an alternative method of MR-based AC in PET/MR
imaging.
PMID- 28517613
TI - A quantitative method to the analysis of MLC leaf position and speed based on
EPID and EBT3 film for dynamic IMRT treatment with different types of MLC.
AB - A quantitative method based on the electronic portal imaging system (EPID) and
film was developed for MLC position and speed testing; this method was used for
three MLC types (Millennium, MLCi, and Agility MLC). To determine the leaf
position, a picket fence designed by the dynamic (DMLC) model was used. The full
width half-maximum (FWHM) values of each gap measured by EPID and EBT3 were
converted to the gap width using the FWHM versus nominal gap width relationship.
The algorithm developed for the picket fence analysis was able to quantify the
gap width, the distance between gaps, and each individual leaf position. To
determine the leaf speed, a 0.5 * 20 cm2 MLC-defined sliding gap was applied
across a 14 * 20 cm2 symmetry field. The linacs ran at a fixed-dose rate. The use
of different monitor units (MUs) for this test led to different leaf speeds. The
effect of leaf transmission was considered in a speed accuracy analysis. The
difference between the EPID and film results for the MLC position is less than
0.1 mm. For the three MLC types, twice the standard deviation (2 SD) is provided;
0.2, 0.4, and 0.4 mm for gap widths of three MLC types, and 0.1, 0.2, and 0.2 mm
for distances between gaps. The individual leaf positions deviate from the preset
positions within 0.1 mm. The variations in the speed profiles for the EPID and
EBT3 results are consistent, but the EPID results are slightly better than the
film results. Different speeds were measured for each MLC type. For all three MLC
types, speed errors increase with increasing speed. The analysis speeds deviate
from the preset speeds within approximately 0.01 cm s-1 . This quantitative
analysis of MLC position and speed provides an intuitive evaluation for MLC
quality assurance (QA).
PMID- 28517616
TI - SU-E-I-95: Multiscale Normalized Metal Artifact Reduction (MS-NMAR) in Computed
Tomography.
AB - PURPOSE: Medical x-ray CT devices produce images of high quality; however, the
metal artifacts may arise from the adverse effect of metal materials present in
the imaged objects. Conventional methods for metal artifact reduction (MAR)
substitute the contaminated projection data corresponding to metal traces by
specific interpolations in the projection space. Nevertheless, these methods
usually introduce new artifacts, because the prior information of the imaged
object (i.e., the prior image) was not involved. Therefore, a normalized MAR
(NMAR) has further been invented, in which the projection space interpolation was
carried out with respect to the ratio (i.e., normalization) of projection raw
data to re-projection of the prior image. This feature renders NMAR a very high
accuracy. However, the normalization in NMAR is more reasonable for the larger
scale contents rather than for the smaller scale details. METHODS: The proposed
MS-NMAR method is a generalization of NMAR with a dedicated multiscale framework.
Both projection raw data and re-projection of the prior image ill be decomposed
into each scale. The normalization followed by the linear interpolation is
performed in each scale, in which the larger the scale is the wider the interval
the linear interpolation is operated with. Composite projection data are acquired
by summing the projection components in all scales. MS-NMAR corrected image is
reconstructed from the composite projection data. RESULTS: Real CT data are used
to verify the efficiency of the proposed method, and to compare with conventional
MAR and NMAR. The quality of reconstructed image after MAR is evaluated by
inspecting the region around the metal material. CONCLUSIONS: Both NMAR and MS
NMAR have a better performance as compared with the conventional MAR. Meanwhile,
MS-NMAR outperforms NMAR, considering it hinders the productions of new artifacts
while reducing the original metal artifacts. This work is partially supported by
the US National Institute of Health through grants P50-AG025688 and 2P50AG025688.
PMID- 28517617
TI - SU-E-I-106: Description of Energy Dose Deposition Kernel for the Diagnostic Beam.
AB - PURPOSE: Over the recent years, the employment of kV x-rays as a diagnostic tool
into clinical routine has resulted in a significant increase in the patient's
exposure to ionizing radiation. The accurate determination of the absorbed dose
to patients during diagnosis is therefore necessary to avoid unnecessary exposure
to the patient. This study presents an analytical model of the energy deposition
kernel for the monoenergetic and polyenergetic kV beams for the fast calculation
of dose in radiography. METHODS: The analytical model is based on the pencil beam
kernels derived from Monte Carlo simulations. DOSXYZnrc code from the EGSnrc
family was employed to simulate the pencil beam of 0.1 cm width for 80, 100 and
120 keV mono-energetic and polyenergetic beams. The lateral dose profiles were
calculated at different depths within a homogenous water phantom of size 50*50*50
cm3 . The evaluated dose profiles showed a high amplitude primary component at
the central axis and a long range low amplitude scatter component spanning a
considerable distance from the central axis. The profiles were fitted
analytically with a triple exponential decay function with an offset. All
coefficients of the exponential function were further fitted with appropriate
analytical functions to represent their behavior relative to depth and photon
energy. The accuracy of the obtained kernel was checked by the convolution of a
rectangular fluence profile and comparing the calculated dose distribution with
the Monte Carlo simulated dose profiles for 2*2 cm2 field size. RESULTS AND
CONCLUSION: In a homogeneous phantom, the comparisons of the convolution method
and Monte Carlo simulations showed sufficient agreement except for largest depths
(deviation approx. 15%). Future developments will focus on an implementation of
the method for dose calculation in the patient.
PMID- 28517618
TI - SU-E-J-02: Accuracy of Fiducial Marker Localization Using Axial and Helical CT,
Cone-Beam CT and KV Imaging.
AB - PURPOSE: To determine localization errors of fiducial markers using axial (ACT)
and helical CT (HCT), cone beam CT (CBCT) and kV imaging. METHODS AND MATERIALS:
A thorax phantom containing markers of various sizes (2.5, 5, 10, 20mm) was
imaged using ACT, HCT, CBCT and kV imaging. The phantom was imaged with and
without motion (15mm amplitude, 15 cycles/min). CT images were reconstructed at
0.625, 1.25, 2.5 and 5mm thickness. Marker location and length were measured
using axial and coronal imaging. RESULTS: The measured marker size increased
almost linearly with increased slice thickness used in CT reconstruction with ACT
for the stationary phantom. In HCT, the marker size varied non-linearly with
increase in slice thickness. Motion of the phantom induced further blurring and
shifts of the center of the marker with different sizes. The 10 mm marker was
elongated up to 13.5 mm and 16.2 mm in the ACT and HCT, respectively. The markers
were elongated up to nearly 26 mm using axial and helical scanning modes by
phantom motion. The displacement of maker center was more prominent in the HCT
with a shift up to 2 mm due to slice thickness for stationary phantom. The marker
center was displaced by up to 18 and 22 mm using ACT and HCT, respectively, which
was even higher than 15 mm motion amplitude. KV imaging produced the sharpest
marker image with the least difference between actual and measured marker sizes.
CONCLUSION: Increase in slice thickness enlarged the apparent marker size and
displaced the maker center in ACT and HCT. Motion led to further enlargement in
the maker size and displacement of maker center that depended on the motion
amplitude. These effects should be considered in CT-based image-guided radiation
therapy to ensure accurate tumor localization and patient positioning with
implanted markers.
PMID- 28517619
TI - SU-E-I-88: Realistic Pathological Simulations of the NCAT and Zubal
Anthropomorphic Models, Based on Clinical PET/CT Data.
AB - PURPOSE: In the present study a patient-specific dataset of realistic PET
simulations was created, taking into account the variability of clinical oncology
data. Tumor variability was tested in the simulated results. A comparison of the
produced simulated data was performed to clinical PET/CT data, for the validation
and the evaluation of the procedure. METHODS: Clinical PET/CT data of oncology
patients were used as the basis of the simulated variability inserting patient
specific characteristics in the NCAT and the Zubal anthropomorphic phantoms. GATE
Monte Carlo toolkit was used for simulating a commercial PET scanner. The
standard computational anthropomorphic phantoms were adapted to the CT data
(organ shapes), using a fitting algorithm. The activity map was derived from PET
images. Patient tumors were segmented and inserted in the phantom, using
different activity distributions. RESULTS: The produced simulated data were
reconstructed using the STIR opensource software and compared to the original
clinical ones. The accuracy of the procedure was tested in four different
oncology cases. Each pathological situation was illustrated simulating a) a
healthy body, b) insertion of the clinical tumor with homogenous activity, and c)
insertion of the clinical tumor with variable activity (voxel-by-voxel) based on
the clinical PET data. The accuracy of the presented dataset was compared to the
original PET/CT data. Partial Volume Correction (PVC) was also applied in the
simulated data. CONCLUSIONS: In this study patient-specific characteristics were
used in computational anthropomorphic models for simulating realistic
pathological patients. Voxel-by-voxel activity distribution with PVC within the
tumor gives the most accurate results. Radiotherapy applications can utilize the
benefits of the accurate realistic imaging simulations, using the anatomicaland
biological information of each patient. Further work will incorporate the
development of analytical anthropomorphic models with motion and cardiac
correction, combined with pathological patients to achieve high accuracy in tumor
imaging. This research was supported by the Joint Research and Technology Program
between Greece and France; 2009-2011 (protocol ID: 09FR103).
PMID- 28517620
TI - SU-E-I-99: An Ultra-High Resolution Small Field-Of-View Solid State X-Ray Imaging
Detector Based on an Electron Multiplying CCD.
AB - PURPOSE: To demonstrate the ultra-high resolution capability of a small field-of
view (FOV) solid state x-ray imaging detector based on an EMCCD sensor. METHODS:
A micro-solid state x-ray image intensifier (micro-SSXII) was developed to serve
as an ultra-high resolution region-of-interest (ROI) imaging detector. It is
based on an 8 micron, 1004 by 1002 pixel electron multiplying CCD (EMCCD)
optically coupled to a 100 micron thick CsI(Tl) phosphor through a fiber optic
window resulting in a FOV of 8 mm. The modulation transfer function (MTF) of the
micro-SSXII was measured by the slanted edge method. A cast of a rat kidney (made
by mixing resin and iodine for contrast) and a mammography line pair test object
were imaged at 50 kVp to demonstrate the detector's ultra-high resolution
capability visually. RESULTS: The MTF was determined and was 5% at 20 cycles/mm.
This is consistent with the clear visualization of the maximum 20 lp/mm group in
the image of the mammography test object. Also, iodine bubbles with diameters as
small as 25 microns, which are formed by the non-uniform mixing of the iodine in
the resin cast, can be clearly identified in the rat kidney vessels. CONCLUSIONS:
The ultra-high resolution capability (>20 lp/mm) but small FOV (8 mm) of the
micro-SSXII in combination with a low-energy x-ray source may have application
for investigations of vascular specimen details and other fine structures where
optical or other surface imagers would be unsuited for evaluating features below
the surface. Contact radiography with this imager combined with a large higher
load focal spot x-ray tube may be a promising substitute for magnification
radiography which is limited by the use of specialized low output microfocus x
ray tubes and geometric un-sharpness for large magnifications. Supported in part
by: NIH Grants R01-EB008425, R01-EB002873 and an equipment grant from Toshiba
Medical Systems Corp.
PMID- 28517621
TI - SU-E-I-66: Is T2 Individual Correction in MRS for Fat Quantification Tool
Necessary?
AB - PURPOSE: In nonalcoholic steatohepatitis (NASH) the fat quantification is
necessary. One of the most used in vivo quantification method is the magnetic
resonance spectroscopy (MRS). It is well known the importance of T2 correction to
improve the accuracy and precision of this method; however the T2 measurements
require time consumption. In this work we estimated the T2 values for water and
fat in NASH patient with different fat contents in order to verify if a generic
T2 correction is adequate for fat quantification in the clinical routine.
METHODS: 19 NASH patients (48+/-10 years, 9 female) underwent MR procedure
several times. Imaging was performed on a 3.0T clinical MRI scanner using a 3P
Dixon method. MRS data was acquired using single voxel (3*3*3 cm) PRESS
acquisition (TR=1500ms, 1024points, 2 KHz bandwidth). The PRESS acquisition was
performed in a single TE (60 ms, 32 averages) and multiple TE (32,45,80 and 135
ms; 16 averages). The software jMRUI was used for peak quantification. The MRS
results were T2 corrected using generic values (T2fat=55ms and T2water=25 ms) for
single TE data and individual values estimated from multi-TE data before fat
fraction calculation. A linear correlation was estimated between the fat fraction
obtained using 3P-Dixon and the spectroscopy methods. RESULTS: The T2 values
estimated were 69+/-14 and 27+/-3 ms for fat and water, respectively. The
correlation coefficients between 3P-Dixon and the spectroscopy methods were: 0.75
for MRS-individual and 0.82 for MRS-general. CONCLUSIONS: The procedure using a
generic T2 value was more correlated to Dixon than one using individual values,
suggesting that is more important a good signal-to-noise ratio than a very
precise T2 value for correction. The reduced range of T2water values doesn't
reflect any considerable iron deposition in NASH patients. In diseases with low
iron deposition it's not necessary the individual T2 correction for fat
quantification from MRS data.
PMID- 28517622
TI - SU-E-I-110: Minimized Pediatric Dose in Direct Radiography (DR).
AB - PURPOSE: Pediatric x-rays techniques are not standardized. They depend upon:
patient size, anatomical localized and equipment manufacturers. Most pediatric
techniques use the default factory settings. This project's goal is to find the
best compromise between dose to pediatric patients and optimal image quality.
METHODS: Low contrast discrimination is the key to image quality. The
manufacturers (Philips and GE) specific techniques were used to establish
baseline values. The following factors were evaluated: kVp, mA, time, use of
grid, collimation, focal spot size, AEC/manual, and added filters. The entrance
skin exposure, entrance exposure to detector, equipment exposure index (EI) and
contrast to noise ratio (CNR) for different thickness from neonatal to average
child were assessed. RESULTS: Overall, some manufacturer's specific pediatric
exposures techniques have higher entrance skin exposure than typical specified
techniques. Equipment reported exposure index are not accurate enough to be used
as 'dosimeter'. Lower kVp, mA with longer exposure time will increase the low
contrast detectability with better CNR but these also change the entrance skin
exposure. Removal of grid, filters do reduce the entrance skin exposure, but
these also reduce low contrast detectability. Focal spot size does not make a big
impact in image quality due to the average detector pixel size. Collimation does
make a difference in AEC sensitivity and exposure index (EI). CONCLUSIONS: There
is no single technique that is the best technique. It is all depend upon many
factors like exam type and the size of the patients. Moreover, it is difficult to
program the generator to use low kVp techniques, add or remove of filters,
collimation, and use of AEC or manual mode, grid on or off in order to optimize
the image quality while minimizing the dose to the patients. Some pediatric
techniques with their associate CNR and radiation dose will be presented.
PMID- 28517623
TI - SU-E-I-76: Optimizing Imaging Parameters for a Novel Radiographic Imaging System
for the Detection of Corrosion in Aluminum Aircraft Structures.
AB - PURPOSE: A laboratory-based phase-contrast radiography/tomosynthesis imaging
system previously (Med. Phys. Vol. 38, 2353 May 2011) for improved detection of
low-contrast soft-tissue masses was used to evaluate the sensitivity for
detecting the presence of thin layers of corrosion on aluminum aircraft
structures. METHODS: The evaluation utilized a test object of aluminum (2.5 inch
* 2.5 inch * 1/8 inch) on which different geometric patterns of 0.0038 inch thick
anodized aluminum oxide was deposited. A circular area of radius 1 inch centered
on the phantom's midpoint was milled to an approximate thickness of 0.022 inches.
The x-ray source used for this investigation was a dual focal spot, tungsten
anode x-ray tube. The focal used during the investigation has a nominal size of
0.010 mm. The active area of the imager is 17.1 cm * 23.9 cm (2016 * 2816 pixels)
with a pixel pitch of 0.085 mm. X-ray tube voltages ranged from 20-40 kVp and
source- to-object and object-to-image distances were varied from 20-100 cm.
Performance of the phase-contrast mode was compared to conventional absorption
based radiography using contrast ratio and contrast-to-noise ratios (C/N). Phase
contrast performance was based on edge-enhancement index (EEI) and the edge
enhancement-to-noise (EE/N) ratio. RESULTS: for absorption-based radiography, the
best C/N ratio was observed at the lowest kVp value (20 kVp). The optimum
sampling angle for tomosynthesis was +/- 8 degrees. CONCLUSIONS: Comparing C/N to
EE/N demonstrated the phase-contrast techniques improve the conspicuity of the
oxide layer edges. This work provides the optimal parameters that a radiographic
imaging system would need to differentiate the two different compounds of
aluminum. Subcontractee from Positron Systems Inc. (Boise, Idaho) through United
States Air Force grant (AF083-225).
PMID- 28517624
TI - SU-E-I-92: Accuracy Evaluation of Depth Data in Microsoft Kinect.
AB - PURPOSE: Microsoft Kinect has potential for use in real-time patient position
monitoring in diagnostic radiology and radiotherapy. We evaluated the accuracy of
depth image data and the device-to-device variation in various conditions
simulating clinical applications in a hospital. METHODS: Kinect sensor consists
of infrared-ray depth camera and RGB camera. We developed a computer program
using OpenNI and OpenCV for measuring quantitative distance data. The program
displays depth image obtained from Kinect sensor on the screen, and the cartesian
coordinates at an arbitrary point selected by mouse-clicking can be measured. A
rectangular box without luster (300 * 198 * 50 mm3 ) was used as a measuring
object. The object was placed on the floor at various distances ranging from 0 to
400 cm in increments of 10 cm from the sensor, and depth data were measured for
10 points on the planar surface of the box. The measured distance data were
calibrated by using the least square method. The device-to-device variations were
evaluated using five Kinect sensors. RESULTS: There was almost linear
relationship between true and measured values. Kinect sensor was unable to
measure at a distance of less than 50 cm from the sensor. It was found that
distance data calibration was necessary for each sensor. The device-to-device
variation error for five Kinect sensors was within 0.46% at the distance range
from 50 cm to 2 m from the sensor. The maximum deviation of the distance data
after calibration was 1.1 mm at a distance from 50 to 150 cm. The overall average
error of five Kinect sensors was 0.18 mm at a distance range of 50 to 150 cm.
CONCLUSIONS: Kinect sensor has distance accuracy of about 1 mm if each device is
properly calibrated. This sensor will be useable for positioning of patients in
diagnostic radiology and radiotherapy.
PMID- 28517625
TI - SU-E-I-59: Investigation of the Usefulness of a Standard Deviation and Mammary
Gland Density as Indexes for Mammogram Classification.
AB - PURPOSE: To investigate the usefulness of the standard deviation of pixel values
in a whole mammary glands region and the percentage of a high- density mammary
glands region to a whole mammary glands region as features for classification of
mammograms into four categories based on the ACR BI-RADS breast composition.
METHODS: We used 36 digital mediolateral oblique view mammograms (18 patients)
approved by our IRB. These images were classified into the four categories of
breast compositions by an experienced breast radiologist and the results of the
classification were regarded as a gold standard. First, a whole mammary region in
a breast was divided into two regions such as a high-density mammary glands
region and a low/iso-density mammary glands region by using a threshold value
that was obtained from the pixel values corresponding to a pectoral muscle
region. Then the percentage of a high-density mammary glands region to a whole
mammary glands region was calculated. In addition, as a new method, the standard
deviation of pixel values in a whole mammary glands region was calculated as an
index based on the intermingling of mammary glands and fats. Finally, all
mammograms were classified by using the combination of the percentage of a high
density mammary glands region and the standard deviation of each image. RESULTS:
The agreement rates of the classification between our proposed method and gold
standard was 86% (31/36). This result signified that our method has the potential
to classify mammograms. CONCLUSIONS: The combination of the standard deviation of
pixel values in a whole mammary glands region and the percentage of a high
density mammary glands region to a whole mammary glands region was available as
features to classify mammograms based on the ACR BI- RADS breast composition.
PMID- 28517626
TI - SU-E-I-70: Semi-Automatic, User-Driven Breast, Chest Wall and FGT Segmentations
Based on Hough Transform, Morphology Tools and Histogram Technology.
AB - PURPOSE: Preliminary analysis shows that breast fibroglandular tissue (FGT) ratio
and background parenchymal enhancement (BPE) of magnetic resonance (MR) imaging
are predictive of future breast cancer risk. Adequate methods for automatic/semi
automatic breast and chest wall segmentation, and FGT histogram extraction and
analysis were not available. METHODS: This method is tested on the retrospective
HIPAA-compliant study, which includes 1275 women who underwent breast MR imaging
between December 2002 and February 2008. The method works in user-directed stages
for each image slice: 1. A straight-line and ellipse Hough transform are applied
to detect chest wall boundaries and separate out the chest region if it is
present. 2. Edge detection and morphology tools are deployed to segment out the
breast region. Human input is required to justify and adjust the segmentation
result. 3. Typical breast MRI histograms have double peaks, of fat regions and
FGT content inside the segmented breast. Human input is needed here to justify
and select a proper segmentation threshold value for whole breast FGT
segmentation. Interactive GUIs were developed in Matlab for all the human input
sections. RESULTS: Various chest wall boundary lines are detected by Hough
transform. Breast region is segmented out either automatically by the morphology
tools or redefined by researchers if there is no proper boundaries available in
the MR images. Breast region is analyzed by histogram technology to separate FGT
from fat. CONCLUSIONS: We have developed a semi-automatic human-guided breast
segmentation method for MRI based on Hough transform, morphology tools and
histogram technology. This approach enables novel breast segmentation and
analysis.
PMID- 28517627
TI - SU-E-I-80: Optimizing Scanning-Beam Digital X-Ray Tomosynthesis of the Lungs.
AB - PURPOSE: We propose to optimize the geometry of the Scanning-Beam Digital
Tomography system (SBDX) for application to lung tumor biopsies, thereby
providing real-time 3D tomographic reconstructions for target verification. The
unique geometry of the system requires trade-offs between patient dose, imaging
field of view and tomosynthesis angle. METHODS: We used PCXMC, a Monte Carlo
simulation software package, to determine the dose to organs of interest as well
as the Average body dose and Effective Dose (both ICRP 60 and 103) for source to
detector distances (SDDs) between 90cm and 150cm. To facilitate modeling our
system, a modified version of PCXMC was created. We also used matlab to evaluate
the possible tomosynthetic angles that Result across the field of view for the
same SDDs. RESULTS: To maximize the tomosynthesis angle while leaving space for
the patient, an SDD of between 90cm and 110cm is appropriate. At SDD 100cm,
patient centered at 40 cm from the detector, operated in fluoro mode, the SBDX
system delivers ~0.38x the dose of a normal mobile fluoroscopy system operating
at 30 fps. Because of the inverse geometry of the system, the dose to the patient
goes up as the patient gets closer to the detector. Tomosynthetic angles up to 15
degrees over a 5-cm field-of-view can be achieved for this geometry. The patient
must be placed within 45cm of the detector in order to achieve the benefits from
reduced SDD and increased tomosynthetic angle. CONCLUSIONS: The dose-rate for our
optimized geometry is acceptable, although higher dose rates for improved nodule
visualization may be required. Additional dose optimization steps include
modifying the scanning beam pattern to optimize for tomosynthetic image
acquisition. Overall dose during the biopsy procedure will likely decrease since
nodule targeting will be improved and the overall number of biopsies required
will be reduced. This work has received funding from NIH grant R21 HL098683, as
well as from the Lucas Foundation.
PMID- 28517628
TI - SU-E-I-63: Performance Study of An Electron-Tracking Compton Camera for Medical
Imaging.
AB - PURPOSE: Conventional gamma-ray detector, PET and SPECT, have the limitation of
energy and field of view. These limitations are major problems of studying for a
new medical imaging. Therefore, we have developed the new imaging detector which
is an electron-tracking Compton camera (ETCC). METHODS: A reconstruction method
of Compton camera (CC) is using the physics principle. Because of using physics
principle, CC can have a wide energy dynamic range and wide field of view.
Conventional CC, however, cannot catch Compton recoil electron tracks, and this
is one of the reasons of low imaging power. We have developed a time projection
chamber (TPC) using micro pixel chamber (MUPIC) as the new detector for ETCC. The
MUPIC is 2-dimensional gaseous detector and this position resolution is less than
400 MUm. Using this detector, ETCC can get electron tracks which are generated
from Compton scattering. In this paper, we show the prototype ETCC performance
and imaging results. RESULTS: ETCC achieved a wide energy dynamic range (200
1300keV) and wide field of view (3 steradian). Also we succeeded in imaging new
imaging reagents using mice as follows; (1) F-18-FDG (511 keV) and I-131-MIBG
(364 keV) simultaneous imaging for double clinical tracer imaging, (2) Zn-65-
porphyrin (1116 keV) imaging for high energy gamma-ray imaging and, (3) imaging
of some minerals (Mn-54, Zn-65) in mice and so on. And we succeeded in 3-D
imaging which has imaged only one direction using one head camera. CONCLUSIONS:
We have developed the ETCC for new medical imaging device and succeeded in
imaging the some imaging reagents. We started to develop the new ETCC which can
image the mouse within 30 min. Thus, this detector has the possibility of new
medical imaging.
PMID- 28517629
TI - SU-E-I-83: Detectability Limits of a New Positron Emission Mammography in
Relation to Tumour-Size, Tumour-To-Background Ratio and Activity Concentration.
AB - PURPOSE: Positron emission mammography (PEM) improves spatial resolution and
sensitivity, making it suitable for early breast tumours detection. The aim of
this study is to evaluate the limits of a dedicated breast PET in terms of tumour
size, tumour-to-background activity concentration ratio (TBR) and activity
concentration. METHODS: A dedicated PEM is evaluated. To characterize the device,
we use a phantom of 15 cm of diameter containing 6 inserts of inner diameters 18,
15, 11, 8, 5 and 3 mm. To evaluate the detectability limits images are acquired
by varying the TBR from 10 to 2 and without background activity concentration. In
all the studies the activity concentration for the 6 inserts is the same (3.7
kBq/ml). To asses the activity concentration limit, the SBR is maintained fixed
and acquisitions at different times are performed. RESULTS: When there is not
background, all the inserts are visible in the PEM. Increasing the background
decreases the detectability. With a SBR of 10, the smaller insert is still
visible. For TBR between 10, inserts >= 5 mm can be seen With a TBR of 2, only
inserts with a diameter higher than 5 mm are visible. When the TBR is fixed,
decreasing the activity concentration, decreases the capability of detectability.
CONCLUSIONS: The results suggest that PEM can be used for diagnosis of small
lesions when TBR is higher than 2. Further clinical studies need to be carried
out in order to validate these results.
PMID- 28517630
TI - SU-E-I-94: External Beam Radiation Cherenkov Emission in Tissue Used for Tissue
Oxygen Sensing.
AB - PURPOSE: To show that Cherenkov emission is generated by external radiotherapy
beam in tissue, and could serve as optical source to excite an oxygen sensitive
phosphor, Oxyphor G4, within tissue. The intensity and lifetime of the
phosphorescence was measured with a time-gated system and reveals the oxygenation
levels in the tissue phantom. METHODS: A tissue phantom made with PBS, 1% v/v
Intralipid-20% (Sigma Aldrich), 1% v/v whole blood and Oxyphor G4 in 1 MUM
concentration is irradiated by 18MeV external radiotherapy electron beam at a
dose rate of 4 Gy/min generated by a medical linear accelerator (Varian LINAC
2100C, Varian Medical Systems). On one side of the phantom, a fiber bundle is
used to conduct optical signal to a spectrometer connected to a fast gating ICCD
(PI-MAX3, Princeton Instruments). For each oxygenation level, a series of
spectrum of phosphorescence at different time points is measured by the time
domain gating technique. Lifetime of phosphorescence is analyzed by exponential
fitting and is validated by comparison to an independent analysis by frequency
domain phosphorimetry. Monte Carlo simulations using GEANT4, of the fiber optic
collection of Cerenkov light were performed to decide the sensitivity of the
optical system for a range of specified geometries and beam types. Simulation
results identify the effective depth within the phantom that is sampled by the
optical collection of the Cerenkov signal. RESULTS: Simulations show that we can
detect the Cherenkov signals comes from an approximately 5 mm depth from within
the tissue phantom. Lifetime of the phosphorescence and pO2 of the phantom could
be measured and calculated correctly by the time domain gating system.
CONCLUSIONS: This work indicates time domain gating techniques combined with an
oxygen sensitive phosphor are capable of accurately monitoring tissue oxygenation
from a reasonable sampling depth in tissue in vivo during external beam
radiotherapy. NIH grant R01CA109558.
PMID- 28517631
TI - SU-E-I-105: Optimizing Bomb Squad X-Ray Systems for Incidental Human Exposures.
AB - PURPOSE: A current terrorist tactic involves strapping an explosive device to a
live victim. Technicians wishing to x-ray the device need to use appropriate
exposures to create clear images while mitigating incidental health problems for
the live victim. This project involves characterizing and optimizing a popular
radiographic system in the explosive investigation community, both for general
use and, more specifically, for generating x-rays with a human subject in the
beam path. This project seeks to minimize the dose to a victim incidentally
located in the beam path, while maximizing image quality, thereby allowing
appropriate image evaluation to neutralize the explosive threat. METHODS: Image
quality and dose optimization begins with characterization of the x-ray source.
The source in this study is an XRS-3, a portable device developed by Golden
Engineering, which nominally produces a 270 kVp beam. Characterization of the
beam involves verifying the actual kVp, as well as determining the average energy
of the beam with various amounts of filtration added to the beam path. The kVp
was verified using a noninvasive technique, utilizing the measurement of the dose
attenuation through lead and then modeling the energy dependent attenuation curve
of the lead using specific mass attenuation coefficients and parameters suggested
by Joseph (Joseph, P.M., Med. Phys. Vol. 2, July/Aug1975; 201-207) in order to
calculate the kVp through linear regression. RESULTS: The average energy of an
unfiltered beam was 52 keV, and increases through adding various combinations of
Cu and brass filters to a maximum value of 121 keV with 3 mm copper + 3 mm brass
filtration. The calculated kVp was 290 kV. CONCLUSIONS: The average energies
using filtration fall within the diagnostic range. The kVp fits well within the
manufacturer's specifications of 15% deviation. Optimization can be accomplished
with these parameters. University of Oklahoma Health Sciences Center- Department
of Radiological Sciences.
PMID- 28517632
TI - SU-E-J-01: Analysis of Acquisition Parameters That Caused Artifacts in Four
Dimensional (4D) CT Images of Targets Undergoing Regular Motion.
AB - PURPOSE: The aim of this study was to clarify the impacts of acquisition
parameters on artifacts in four-dimensional computed tomography (4D CT) images,
such as the partial volume effect (PVE), partial projection effect (PPE), and mis
matching of initial motion phases between adjacent beds (MMimph) in cine mode
scanning. METHODS: A thoracic phantom and two cylindrical phantoms (2 cm diameter
and heights of 0.5 cm for No. 1 and 10 cm for No.2) were scanned using 4D CT. For
the thoracic phantom, acquisition was started automatically in the first scan
with 5 sec and 8 sec of gantry rotation, thereby allowing a different phase at
the initial projection of each bed. In the second scan, the initial projection at
each bed was manually synchronized with the inhalation phase to minimize the
MMimph. The third scan was intentionally un-synchronized with the inhalation
phase. In the cylindrical phantom scan, one bed (2 cm) and three beds (6 cm) were
used for 2 and 6 sec motion periods. Measured target volume to true volume ratios
(MsTrueV) were computed. The relationships among MMimph, MsTrueV, and velocity
were investigated. RESULTS: In the thoracic phantom, shorter gantry rotation
provided more precise volume and was highly correlated with velocity when MMimph
was minimal. MMimph reduced the correlation. For moving cylinder No. 1, MsTrueV
was correlated with velocity, but the larger MMimph for 2 sec of motion removed
the correlation. The volume of No. 2 was similar to the static volume due to the
small PVE, PPE, and MMimph. CONCLUSIONS: Smaller target velocity and faster
gantry rotation resulted in a more accurate volume description. The MMimph was
the main parameter weakening the correlation between MsTrueV and velocity.
Without reducing the MMimph, controlling target velocity and gantry rotation will
not guarantee accurate image presentation given current 4D CT technology.
PMID- 28517633
TI - SU-E-I-87: Tumor Positioning for PET-CT Scanner by Jointly Registration and
Segmentation.
AB - PURPOSE: In order to achieve tumor positioning for radiotherapy planning
automatically and accurately, an efficient tumor positioning method is proposed
by jointly registration and segmentation for 18F-FDG PET-CT scans. METHODS: At
the first stage, the tumor is segmented from PET scans by region growing using
the manual seeds which employs the SUV monotonous features, and then the tumor
contours are transferred to corresponding CT images automatically for following
radiation therapy planning by a new deformable registration method which is
implemented by combining edge preserving scale space with the free form
deformation. The edge preserving scale space which is able to select edges and
contours of an image according to their geometric size is derived from the total
variation model with the L1 norm (TV-L1). At each scale, the selected edges and
contours are sufficiently strong to drive the deformation using the FFD grid,
then the deformation fields are gained by a coarse to fine manner.Datasets were
collected from 5 patients treated under the PET-CT scanner (GE medical systems,
Discovery LS). Before treatment planning, the GTV (gross tumor volume) is
delineated on every section of the PET scans by the radiation oncologist and the
Result will be compared with proposed automatic segmentation method. Of the 5
patients investigated here, all are non-small cell lung carcinoma (NSCLC)
patients. RESULTS: After evaluation of the experiment results by three clinical
oncologists, they concluded that the segmentation results are very close to the
manual results and the GTV contours on CT scan which is produced by the
deformation field automatically can be used for radiation therapy planning. The
volumetric overlap is on an average 90%-97% comparing with manually segmented
tumors by oncologists. CONCLUSIONS: We can conclude that an efficient tumor
positioning method is proposed by jointly registration and segmentation for FDG
PET-CT datasets.
PMID- 28517634
TI - SU-E-I-98: PET/CT's Most-Cited 50 Articles since 2000: A Bibliometric Analysis of
Classics.
AB - PURPOSE: Despite its relatively recent introduction to clinical practice, PET/CT
has gained wide acceptance both in diagnostic and therapeutic applications.
Scientific publication in PET/CT has also experienced significant development
since its introduction. Bibliometric analyses allow an understanding of how this
publication trend has developed at an aggregated level. Citation analysis is one
of the most widely used bibliometric tools of scientometrics. Analysis of
classics, defined as an articles with 100 or more citations, is common in the
biomedical sciences as it reflects an article's influence in its professional and
scientific community. Our objective was to identify the 50 most frequently cited
classic articles in PET/CT in the past 10 years. METHODS: The 50 most-cited
PET/CT articles were identified by searching ISI's Web of Knowledge and Pubmed
databases for all related publications from 2000 through 2010. Articles were
evaluated for several characteristics such as author(s), institution, country of
origin, publication year, type, and number of citations. An unadjusted
categorical analysis was performed to compare all articles published in the
search period. RESULTS: The search yielded a cumulative total of 22,554 entries
for the publication period, of which 15,943 were original research articles. The
50 most-cited articles were identified from the latter sum and selected out of 73
classics. The number of citations for the top 50 classics ranged from 114 to 700.
PET/CT classics appeared in three general and 12 core journals. The majority of
the classics were in oncologic applications of PET/CT (62%). Articles related to
diagnostic topics were 6%. The rest were focused on physics and instrumentation
24% and other basic sciences 16%. CONCLUSIONS: Despite its relatively short
history PET/CT accumulated 73 classic articles in a decade. Such information is
of importance to researchers and those who wish to study the scientific
development in the field.
PMID- 28517635
TI - SU-E-I-65: Magnetic Resonance Spectroscopy of the Prostate: A Phantom Study of
Metabolite Concentrations.
AB - PURPOSE: Magnetic Resonance Spectroscopy (MRS) of the prostate is not used in
radiotherapy departments on a regular basis due to a number of issues. The
indication and severity of prostate cancer is related to the presence of choline
in the prostate, in particular, the ratio of choline (plus creatine) to citrate.
In-vivo data supports this theory only marginally but lacks strong correlation
with biopsy data. The situation is further complicated by the lack of precise
spatial information in biopsy, variation of magnetic susceptibility, and spatial
dependence of MRS data on the distance from the endo-rectal coil. The latter also
cause low signal-to-noise ratio (SNR). We intend to understand how the level of
metabolite concentrations and spatial dependences determine what is observed in
MRS. METHODS: A spherical phantom is filled with water solutions containing
various amounts of metabolites. It is placed on top of an endo-rectal coil with
the balloon filled with per fluorocarbon. MRS data is acquired on a GE 1.5 T MR
scanner. The metabolite values, their ratios etc as reported in GE software,
FuncTool are studied as functions of metabolite concentrations in the phantom.
RESULTS: Analysis of the phantom data indicates that the metabolite ratio
reported in FuncTool is approximately linearly correlated to the metabolite
concentrations used in the phantom to a certain point and then saturates whereas
the largest metabolite value is well correlated with its concentration in the
phantom. All metabolite values become weaker and SNR lower as we move away from
the coil. CONCLUSIONS: This work indicates the potential of using metabolite
values directly provided their spatial dependences on the distance of the voxels
from the endo-rectal coil can be accommodated.
PMID- 28517636
TI - SU-E-I-109: Sensitivity Analysis of an Electronic Portal Imaging Device Monte
Carlo Model to Variations in Optical Transport Parameters.
AB - PURPOSE: To investigate the sensitivity of a Monte Carlo (MC) model of a standard
clinical amorphous silicon (a-Si) electron portal imaging device (EPID) to
variations in optical photon transport parameters. METHODS: The Geant4 MC toolkit
was used to develop a comprehensive model of an indirect-detection a-Si EPID
incorporating x-ray and optical photon transport. The EPID was modeled as a
series of uniform layers with properties specified by the manufacturer
(PerkinElmer, Santa Clara, CA) of a research EPID at our centre. Optical
processes that were modeled include bulk absorption, Rayleigh scattering, and
boundary processes (reflection and refraction). Model performance was evaluated
by scoring optical photons absorbed by the a-Si photodiode as a function of
radial distance from a point source of x-rays on an event-by-event basis (0.025
mm resolution). Primary x-ray energies were sampled from a clinical 6 MV photon
spectrum. Simulations were performed by varying optical transport parameters and
the resulting point spread functions (PSFs) were compared. The optical parameters
investigated include: x-ray transport cutoff thresholds; absorption path length;
optical energy spectrum; refractive indices; and the 'roughness' of boundaries
within phosphor screen layers. RESULTS: The transport cutoffs and refractive
indices studied were found to minimally affect resulting PSFs. A monoenergetic
optical spectrum slightly broadened the PSF in comparison with the use of a
polyenergetic spectrum. The absorption path length only significantly altered the
PSF when decreased drastically. Variations in the treatment of boundaries
noticeably broadened resulting PSFs. CONCLUSIONS: Variation in optical transport
parameters was found to affect resulting PSF calculations. Current work is
focusing on repeating this analysis with a coarser resolution more typical of a
commercial a-Si EPID to observe if these effects continue to alter the EPID PSF.
Experimental measurement of the EPID line spread function to validate these
results is also underway. Cancer Institute NSW Research Equipment Grants 10/REG/1
20 and 10/REG/1-10 Cancer Council NSW Grant, ID RG 11-06 NHMRC Project Grant,
ID569211 The University of Sydney Postgraduate Research Scholarship in Medical
Physics SWSCS Radiation Oncology Student Scholarship, 2012.
PMID- 28517637
TI - SU-E-I-75: A New Method for Prostate Cancer Localization Using Multispectral MRI.
AB - PURPOSE: To develop a new method for automatic localization of prostate cancer
using multispectral MRI data. METHODS: Multispectral MRI including MR
spectroscopic imaging (MRSI), T2 weighted MRI, diffusion weighted imaging (DWI)
and dynamic contrast-enhanced (DCE) MRI, has been used for cancer target
localization. The combination of multiple MRI imaging technologies provides more
useful information than one single technology alone about prostate cancer and has
advantages for target definition in radotherapy treatment and quantitative
evaluation of tumor response. However, manual cancer localization using
multispectral MRI dataset is a tedious task and prone to inter-/intra-observer
variability. Automatic localization methods using multispectral MRI data is
highly desired. In this paper, a fuzzy fusion framework for automatically
localizing prostate cancer with multispectral MRI data is presented. Firstly, for
each kind of MRI images, a membership function is created to calculate the
membership-degrees of image elements belonging to cancer region. Secondly, a
fuzzy fusion operator is used to fuse different membership- degrees corresponding
to the same regions. Lastly, the Result of fusion is further adjusted with fuzzy
region growing process, leading to the final membership-degree map. And cancer
volume is finally defined by setting up a threshold on the map. RESULTS: The new
method was tested with one multispectral MRI patient dataset and results from our
experimental study are compared with the one obtained form a manual method
performed by an experienced pathologist. Quantitative analysis shows that the
specificity is 98.89%, sensitivity is 62.85% and accuracy is 95.42%,
respectively. It illustrates the feasibility of utilizing this framework in the
clinical application. CONCLUSIONS: The feasibility study shows the new method
reported in this paper achieves automatic localization for prostate cancer and
can be easily implemented in clinical applications. We are currently conducting a
clinical study for testing the effectiveness and reliability, and further
developing this method. *supported by NSFC-81171342 support by National Science
Foundation of China (NSFC-81171342).
PMID- 28517638
TI - SU-E-I-91: Development of a Compact Radiographic Simulator Using Microsoft
Kinect.
AB - PURPOSE: Radiographic simulator system is useful for learning radiographic
techniques and confirmation of positioning before x-ray irradiation. Conventional
x-ray simulators have drawbacks in cost and size, and are only applicable to
situations in which position of the object does not change. Therefore, we have
developed a new radiographic simulator system using an infrared-ray based three
dimensional shape measurement device (Microsoft Kinect). METHODS: We made a
computer program using OpenCV and OpenNI for processing of depth image data
obtained from Kinect, and calculated the exact distance from Kinect to the object
by calibration. Theobject was measured from various directions, and positional
relationship between the x-ray tube and the object was obtained. X-ray projection
images were calculated by projecting x-rays onto the mathematical three
dimensional CT data of a head phantom with almost the same size. The object was
rotated from 0 degree (standard position) through 90 degrees in increments of 10
degrees, and the accuracy of the measured rotation angle values was evaluated. In
order to improve the computational time, the projection image size was changed
(512*512, 256*256, and 128*128). RESULTS: The x-ray simulation images
corresponding to the radiographic images produced by using the x-ray tube were
obtained. The three-dimensional position of the object was measured with good
precision from 0 to 50 degrees, but above 50 degrees, measured position error
increased with the increase of the rotation angle. The computational time and
image size were 30, 12, and 7 seconds for 512*512, 256*256, and 128*128,
respectively. CONCLUSIONS: We could measure the three-dimensional position of the
object using properly calibrated Kinect sensor, and obtained projection images at
relatively high-speed using the three-dimensional CTdata. It was suggested that
this system can be used for obtaining simulated projection x-ray images before x
ray exposure by attaching this device onto an x-ray tube.
PMID- 28517639
TI - SU-E-I-102: Independent Implementation of AAPM TG-150 Draft Image Receptor Test
Recommendations.
AB - PURPOSE: To determine whether a proposed suite of generic tests for digital
radiography (DR) detectors could be reduced to practice. METHODS: MATLAB software
was developed to analyze images according to descriptions in a document drafted
by the TG150 Detector Subgroup. Forprocessing images were acquired directly from
the acquisition stations of three DR and one Computed Radiography system. Images
included flat-field exposures at the manufacturer's calibration condition, twice
the exposure, 1/2 the exposure, and a low exposure, plus three images of a lead
bar pattern in different orientations, also at the calibration condition. The
flat field images were analyzed to determine Detector Response; Gain Correction;
Signal, Noise, and Signal-to-noise (SNR) Uniformity; SNR Magnitude; and Anomalous
Detector Element (del) Identification. The program also allowed visual inspection
for evaluation of collimation and non-uniformity. Bar pattern images were
analyzed to evaluate spatial resolution by a variance method. RESULTS:
Acquisition revealed a number of pitfalls. Some manufacturers have multiple
calibration points. For-processing images are not directly available from all
systems, and PACS may modify them from their original state. The orientation of
the flat field with respect to the anodecathode axis may not be defined by the
manufacturer. Care must be taken to ensure collimation outside the edges of
detectors, or the software must exclude collimator shadows. The matrix size of
images differs among manufacturers, so the size of the region of interest (ROI)
for analysis varies from the default size of 100*100 dels, as does the number of
ROIs. The approach for dealing with edges and ROIs may affect the numerical
results. The detector response function may also affect the interpretation of
results. CONCLUSIONS: The software successfully implements most of the detector
tests recommended by TG150. Comparison of these results with those of the
parallel effort will validate the draft test definition.
PMID- 28517640
TI - SU-E-I-69: Magnetic Resonance Metal Artifact Evaluation with Routine Clinical
Cardiac Sequences.
AB - PURPOSE: To examine schemes to grade the severity of metal susceptibility
artifacts on image quality using cardiac MRI pulse sequences. METHODS: A post
thoracotomy patient was simulated with a stainless steel sternal wire
(Syneture,MA; size=6, diameter=48mm), placed securely on an ACR MRI phantom.
Phantom was scanned on a 1.5-T Siemens using cardiac MRI sequences:1)TrueFISP,
2)Gradient-Recalled-Echo (GRE), 3)Turbo-Spin- Echo (TSE), 4)Turbo-Inversion
Recovery-Magnitude (TIRM), 5)Dark- blood-IR-FS (DBFS) with and without the wire
(FOV=30*30cm, slice- thickness/slice-gap=7.0/1.5mm, matrix size=192*192,
slices=17). Image quality degradation was assessed in terms of signal loss and
spatial deformation; signal loss by a) measuring the largest diameter of signal
drop and b) number of slices with a signal drop and spatial deformation in
VelocityAI (Atlanta,GA) by computing the rigid transformation indices between the
phantom's internal grid with and without the metal. RESULTS: Image quality was
evaluated in terms of signal loss, spatial deformation and ring artifacts. Signal
loss: TruFISP and GRE showed the largest signal drop diameter (13 and 16cm
respectively). GRE sequence showed a signal drop in -12 slices where as signal
drop occurred in only ~4-5 slices with other sequences. Spatial deformation: GRE
sequence showed the maximum with a ~9mm grid deflection followed by TSE and DBFS
(~8mm). An average deflection of 5.4mm was observed on most of the sequences
except T rueFISP and TIRM (Omm). Rigid body transformation showed a maximum x,y,z
translation of -4.7, 0.3 and 1.69 mm and x,y,z-angular rotation of 0.2, - 1.5 and
0.5 degrees for GRE sequence followed by TSE and DBFS confirming the spatial
distortion results. Concentric ring artifacts with signal loss were also observed
on TrueFISP and DBFS images. CONCLUSIONS: Quantification of cardiac MR sequences
to metal tolerance and the impact on image quality has shown that GRE and
TrueFISP are the most metal-susceptible and TIRM is the most metal-tolerant
sequence in terms of both signal loss and spatial deformation. This study helped
in creating a separate cardiac metal protocol comprising of mainly metal-tolerant
sequences thus reducing scan time and patient discomfort.
PMID- 28517641
TI - SU-E-I-79: Correction of Dark Current and Image Lag in Multi-Source Carbon
Nanotube Imaging Systems.
AB - PURPOSE: To correct for dark current and detector image lag in multi-source
carbon nanotube (CNT) based imaging systems. METHODS: CNTs can be used as a novel
electron source for X-ray generation. Here a small (~2 kV) gate voltage induces a
large electric field at the CNT tip that causes field emission as opposed to
thermionic emission. This enables faster switching times and allows
miniaturization which aids in the development of stationary multi-source systems.
These systems may encounter two key problems: dark current in non-active sources
and detector lag. In damaged and perhaps end-of-life devices, sources may develop
significant electron output without gate voltage, interfering with images from
non-active sources. Although the output is small, it is constant, and continuous
integration of detectors compared with small X-ray exposure time magnifies its
contribution to the signal. A method based on binary multiplexing is developed to
mitigate the dark current contributions possibly extending device lifetime.
Having discrete sources, these multi-source systems have coarser angular sampling
than rotating systems. This coarser sampling means that the detector signal
changes more in adjacent projections than rotating systems exacerbating the
effect of detector lag. Since flat panel detectors have a capacitive behavior,
readout only removes some charge from pixels. As a result, a device dependent
amount (6.6% in our device) of the signal from the current image contributes to
the subsequent image. A fast, stable inverse filter separating detector lag has
been developed. RESULTS: Projection data were simulated based on parameters
measured from a multi-source CNT system. Incorporating dark current and image lag
phenomena into reconstruction improves contrast to noise ratio. CONCLUSIONS:
These correction methods can be easily implemented on clinical multi-source
systems to improve image quality and extend the device's usable lifetime.
Supported in part by Siemens Medical.
PMID- 28517642
TI - SU-E-I-62: Investigation of Dominant Factors Affecting Fatigue in Image Reading
of Radiologists.
AB - PURPOSE: To investigate dominant factors affecting fatigue in image reading of
radiologists. METHODS: Two kinds of fatigue were assessed in this study. One was
fatigue in the central nervous system evaluated by the critical fusion frequency
(CFF). The other was eye fatigue evaluated by a score determined from a
questionnaire based on the oculomotor strain subscale from the Simulator Sickness
Questionnaire (SSQ). When fatigue increases, the CFF and the SSQ score indicate
low and high values, respectively. The fatigue of seventeen radiologists was
assessed before and after their daily image reading. The reading times and the
numbers of images were different among the assessments, and ranged about 1.5 -
5.0 hours and 1,000 - 12,000 images, respectively. The assessments of fatigue
were repeated four times for each radiologist on different days. Finally, the
measurements of the two kinds of fatigue were analyzed in terms of years of
experience, age, sleeping time the previous night, ambient light conditions,
reading time, and the numbers of interpreted images, series, and cases. RESULTS:
The CFF and SSQ score after image reading were significantly lower and higher
than those measured before image reading, respectively. Younger and less
experienced radiologists indicated a higher level of fatigue than older and more
experienced radiologists in both the CFF and the SSQ score. When radiologists
interpreted clinical images for longer hours, the SSQ score tended to be higher.
On the other hand, there was little incremental difference in the CFF among
different lengths of reading time. No obvious differences were observed in the
other items. CONCLUSIONS: Less experience with reading images, a younger age, and
a longer reading time could be dominant factors affecting fatigue in image
reading.
PMID- 28517643
TI - SU-E-I-72: Modulation of Hypothalamic Connectivity by Food Ingestion.
AB - PURPOSE: In this study we utilized resting state fMRI (rsfMRI) to identify and
compare hypothalamic connectivity in lean subjects during fasting and satiated
state. METHODS: rsfMRI were performed on 7 healthy lean subjects (4 male, 3
female, 20-35 yo, BMI = 18-25 kg/m2 ). Subjects fasted overnight (8 hrs), average
blood glucose of 80+/- 5 mg/dL. None of the subjects were on diet program or
recently lost/gain weight. rsfMRI EPI parameters:TR = 3000ms, TE = 30 ms, and
spatial resolution of 1.7 * 1.7 mm * 5mm, ST= 65 mins (10-min pre-glucose
ingestion acquisition, followed by 50 mins of post-glucose ingestion). During
rsfMRI, subjects ingested standard glucola (75 g of glucose dissolved in 296 ml
of flavored water) over 4.5 +/- 0.75 min via a peroral rubber tube. Preprocessing
procedure was implemented using FSL consisting of 1) motion correction 2) spatial
smoothing, 3) temporal filtering between 0.01-0.08 Hz. Using the Talairach-Daemon
atlas, ROI in the hypothalamus was selected. The individual timeseries of
hypothalamus was used as seed to find neural structures that share similar
temporal pattern that hypothalamus. RESULTS: Structures that were engaged only
during fasting were (Table 1): Inferior frontal gyrus (BA 47) has been linked to
the modulation of hunger. The output from the orbitofrontal cortex to both
striatum (lentiform nucleus) and lateral hypothalamus has been reported. The
structures that were engaged only during satiated state were: Superior temporal
gyrus has been implicated in food inhibition and mid temporal gyrus has been
reported to be engaged in satiation. Cerebellum is activated when the brain is
monitoring its sensory systems.
PMID- 28517645
TI - SU-E-I-104: Detector Lag Testing for Digital Radiography.
AB - PURPOSE: Signal lag is an inherent property of the digital detectors used for
radiography. The extent and impact of signal lag can vary. In this exhibit we aim
to:'c provide context for detector lag testing as a matter of acceptance testing
for detectors used in digital radiography (DR)'c provide example lag data from
various DR systems. Lag measurement and analysis techniques have been published
but without the expected results that are useful for benchmarking.'cbring greater
awareness and understanding to the impact of detector lag for the performance of
digital detectors and the appearance of image ghosting in clinical images.
METHODS: A standardized method was used for the quantification of lag similar to
that described in the IPEM report 32 part vii [1]. Six different vended detector
options were measured and compared. RESULTS: Lag images were visually compared
and lag measurement values were normalized using the measured signal transfer
properties of each system. The results are shown as normalized with exposure. The
results show a wide variety of lag responses, even for the same physical detector
hardware but different vendor implementations. CONCLUSIONS: The ultimate test for
detector lag performance is whether residual 'ghost' images appear in clinical
images. Some vendor systems are more prone to the appearance of lag than others.
We attempt to quantify system properties at acceptance testing that can enable
discriminationbetween systems which have poor or superior lag properties. A
suggested easurement analysis technique which normalizes data to be linear with
exposure does not appear to adequately assess the likelihood for the clinical
appearance of lag. [1] Mackenzie A et al. Measurement of the Performance
Characteristics of Diagnostic X-Ray Systems: Digital Imaging Systems. Institute
of Physics in Medicine 2009 (IPEM Report 32, part vii). 2010.
PMID- 28517646
TI - SU-E-I-115: Wavelet Analysis of Ultrasound Image for the Diagnosis of Sjogren's
Syndrome.
AB - PURPOSE: Sjogren's syndrome (SS) is an auto-immune disease presenting with dry
eyes and mouth (keratoconjunctivitis sicca and xerostomia). Ultrasonography is
used for the initial and non-invasive investigation of the parotid gland in the
disease. The purpose of this study is to develop an image processing for
diagnosis of SS by applying wavelet analysis to ultrasound image. METHODS:
Ultrasound B-mode images of the parotid gland were captured and analyzed by a
personal computer. A square region of interest (ROI) was set on the image and two
dimensional discrete wavelet transform was performed within the ROI. As a Result,
the image was decomposed into an approximate image and three detailed images in
vertical, horizontal and diagonal directions in different scales. A feature
quantity for image classification was defined by calculating from the wavelet
coefficients of detailed images within selected scales. The ultrasound images of
80 patients who had been referred to Nagasaki University Hospital because of
suspicion of SS were analyzed. A total of 37 patients fulfilled the criteria for
SS, whereas the remaining 43 patients did not. The severity of SS was graded into
four degrees by sialography. The images with each feature quantity were
classified by statistical cluster analysis. RESULTS: In this method, the images
can be divided into two groups which mainly contained SS and non-SS. The
sensitivity and specificity in the detection of SS was 78% and 95%, respectively.
It was also found that the defined feature quantity tended to change with the
severity of SS. CONCLUSIONS: In ultrasonography, the image analysis based on
wavelet transform was useful for the diagnosis of Sjogren's syndrome.
PMID- 28517647
TI - SU-E-I-86: Image Fusion Verification Using a Vendor-Independent Phantom.
AB - PURPOSE: To evaluate the image fusion accuracy of a hybrid PET/CT or SPECT/CT
system using a recently developed vendor-independent phantom. METHODS: The basic
design of the fusion verification phantom is a 10 cm urethane cube with three 1
mm diameter channels each fitted with standard Luer connection designed to be
filled with a radioactive solution. The channels also have a 0.4 mm diameter
steel wire inserted in each channel. There are two versions of this cube phantom
with different orientations of the wire/liquid filled channels. There is the
perpendicular cube with three channels each parallel to the x, y and z axes. The
second cube orientation has two opposing angled channels and one that is
perpendicular to the cube base. When imaged with either a PET/CT or SPECT/CT
device the wire yields a high contrast image against a high signal target of the
radioisotope filled channel. Both phantoms are scanned on various vendor and
model hybrid systems. RESULTS: Three plane reconstructed data of the
perpendicular fusion phantom generates images with point source like targets of
the emission and transmission data for quick visual evaluation of registration
accuracy for x, y and z shifts. A series of axial reconstructed images can be
used to evaluate alignment when using the opposing ramp fusion phantom. The
unique utility of the opposing ramps allows for verification of a z-axis offset
from the single axial image data. Alignment data are presented from a number of
PET/CT and SPECT/CT systems. CONCLUSIONS: The use of either the perpendicular or
opposing ramp fusion phantom provides a convenient QC vendor independent tool for
evaluation of image alignment accuracy of hybrid imaging systems. The design
supports a simple 3D processing with a straightforward visual interpretation of
alignment.
PMID- 28517649
TI - SU-E-I-64: 1H-MRS Quality Assurance in Short and Long Term Using a Phantom
Object.
AB - PURPOSE: To evaluate intrinsic variability of 1H-MRS single voxel technique for
short and long periods of time using a metabolic phantom in a clinical protocol
(hippocampi). METHODS: A solution with several metabolites (NAA, Cre, Cho, Lac, M
Ins, Glu, Gln) was placed in a spherical round glass with 300 mL. MRS data were
acquired in a 3 T MRI scanner, with a PRESS sequence of TE/TR=35/1500 ms, 2048
data points, 1725 Hz of bandwidth, 6 cm3 VOI centered in the phantom and NSA of
128. A total of 130 spectra were obtained from 27 acquisition dates (5
spectra/date without removing the phantom) over 15 months. Spectra were processed
with LCModel software to reduce the human variability during spectra processing.
SNR and FWHM outputs from LCModel are mean calculated values from identified
resonances. RESULTS: Spectra from each acquisition date showed no mean deviations
superior to 4% for all metabolites except for Lac (14 %). During 15 months all
metabolites showed inferior deviations to 12%, once again except for Lac (20.5%).
The worst estimated concentration was from Gln, which represent 60% of the
expected value. The mean SNR was 16.3+/-2.1. There was no correlation between SNR
and mean FWHM from resonances, thus wrong water suppression must be the main
factor for variable SNR. CONCLUSIONS: NAA was the most stable metabolite in the
whole analysis period with a variation of 6.8%, and Gln was the less stable with
a 25.4% variation. FWHM was more variable than SNR, possible due to shimming
variability, although it showed no influence in SNR. It was observed two types of
artifacts in some spectra generated by unbalanced gradients, B0 inhomogeneity and
also insufficient amplitude from crusher gradients. Temporal analysis
demonstrated the feasibility of compare results obtained on measurements of the
same date and for long periods due to low deviations provided by the technique.
PMID- 28517650
TI - SU-E-I-108: Simple Approach to Determine Patient's Entrance Skin Exposure for
Radiographic.
AB - PURPOSE: To evaluate a model which can predict patient's Entrance Skin Exposure
(ESE) from height and weight and a single kVp mR/mAs measurement for
radiographic. METHODS: Patient height, weight and post exposure mAs are obtained
to assess ESE based on IAEA model. Patient's thickness is obtained by assuming a
cylindrical geometry. The validity of this assumption is tested against actual
measurements. Source to Skin Distance (SSD) is computed from patient's thickness
and the Source-Image receptor Distance (SID) used during exposure. Entrance Skin
Exposure is calculated as a product of post exposure mAs and a single 80 kVp
mR/mAs obtained at a reference distance corrected inversely for SSD. Values of
mR/mAs at other kVp's are obtained by quadratic variation of output with kVp.
RESULTS: The validity of predicting patient thickness will be presented based on
numerous measurements performed on test subjects. Deviation between the ESE
values using of single kVp, mR/mAs measurement and the ones obtained by the
conventional multiple kVp mR/mAs will be presented as well. CONCLUSIONS: This
work indicates a simple approach to determine the patient's ESE based on the
patient's height and weight for radiographic units, which will be very useful for
institutions that do not have a dedicated physicist.
PMID- 28517648
TI - SU-E-I-97: Characterizing the Modulation Transfer Function (MTF) of Proton
Radiography.
AB - PURPOSE: To characterize the modulation transfer function (MTF) of proton
radiography using GEANT4 Monte Carlo simulations. METHODS: A phantom was
specifically modeled using five main materials: bone (1.92 g/cm3 ), muscle (1.2
g/cm3 ), water (1.0 g/cm3 ), adipose tissue (0.9 g/cm3 ), and lung (0.3 g/cm3 ).
The basic geometry of the phantom consists of cube-shaped inserts of biological
materials placed in water. The thickness of the water, the size of the cube, the
depth of the cube in the water, and the proton beam energy have all been varied
and studied. The contrast-to-noise ratio (CNR) between the two materials was
evaluated at multiple points along a line-of-interest (LOI) in order to
ultimately characterize the spatial resolution by the 10% point of the modulation
transfer-function (MTF10% or MTF 10). RESULTS: The MTF was generated for
interfaces of water-lung, water-bone, water-muscle, water-adipose. This study
indicates that proton radiography can distinguish one material from another with
a resolution better than 1 mm for water-adipose and water-muscle or sub
millimeter in cases of water-bone and water-lung interfaces. CONCLUSIONS: The sub
millimeter resolution of proton radiography offers clinicians a potentially tool
in specific tumor diagnostics (such as in lung cancer), patient-setup for daily
proton therapy, and the reduction of absorbed dose delivered when compared to
photon imaging.
PMID- 28517651
TI - SU-E-I-74: White Matter Tract Disintegrate of Frontal and Limbic Regions in Mild
Cognitive Impairment with Depression.
AB - PURPOSE: Mild cognitive impairment with depression (MCID) is common and
associated with disability and cognitive impairment, with high probability of
relapse. Hypothesize that 1) a sign of WM disintegration would be observed in
MCID than MCI nondepression (MCIND), especially in frontal and limbic regions and
patients with depression would show reduced GM density in the hippocampus,
amygdala, anterior gyrus cingulate, and dorsolateral prefrontal cortex (DLPFC)
and dorsomedial prefrontal cortex (DMPFC) 2) the abnormalities of long
association fiber tracts integrity are correlated with geriatric depression.
METHODS: Forty-two subjects (20 nondepressed, 22 depressed) underwent DTI and
cognitive assessment. Depression was initially assessed by means of the Korean
version of the 30-item Geriatric Depression Scale (K-GDS). All patients scoring
19 or higher on the K-GDS were screened as depressed. An automated tract-based
statistical analysis method was used to derive estimates of fractional anisotropy
(FA) for each subject. Group effects and correlations with clinical features on
DTI parameters were examined. RESULTS: We found cross-sectional differences in WM
tract disintegration on posterior cingulum, splenium of corpus callosum, uncinate
fasciculus, genu, thalamus, internal and external capsule of limbic in MCID.
These results support changes in the structural integrity of neuronal cells in
these specific important brain regions constituting a fronto-limbic-cerebellar
network during depressive and in particular during the course of depression. The
different parts of the frontal lobes have afferent and efferent connections with
other neocortical, limbic, and subcortical regions and participate in the limbic
cortico-striatal-pallidal-thalamic circuits. CONCLUSIONS: Findings are suggestive
of loss of integrity in WM fiber within frontal, temporal and limbic regions,
increasing the evidence that implicates disruptions to the limbic-orbitofrontal
networks in the pathogenesis of MCID. These neuroanatomical circuits play an
important role in the regulation and modulation of affect and emotion, and
contribute to the pathogenesis of late-life depression.
PMID- 28517652
TI - SU-E-I-90: Fast and Robust Algorithm Towards Vessel Lumen and Stent Strut
Detection in Optical Coherence Tomography.
AB - PURPOSE: Optical Coherence Tomography (OCT) is a catheter-based imaging method
that employs near-infrared light to produce high-resolution cross-sectional
intravascular images. We propose a new segmentation technique for automatic lumen
area extraction and stent strut detection in intravascular OCT images for the
purpose of quantitative analysis of neointimal hyperplasia (NIH). METHODS: Two
clinical dataset of frequency-domainOCT scans of the human femoral artery were
analyzed. First, a segmentation method based on Fuzzy C-Means (FCM) clustering
and Wavelet Transform (WT) was applied towards inner luminal contour extraction.
Subsequently, stent strut positions were detected by utilizing metrics derived
from the local maxima of the wavelet transform into the FCM membership function.
RESULTS: The inner lumen contour and the position of stent strut were extracted
with very high accuracy. Compared with manual segmentation by an expert
physician, the automatic segmentation had an average overlap value of 0.917 +/-
0.065 for all OCT images included in the study. The strut detection procedure
successfully identified 6.7 +/- 0.5 struts for each OCT image. CONCLUSIONS: A new
fast and robust automatic segmentation technique combining FCM and WT for lumen
border extraction and strut detection in intravascular OCT images was designed
and implemented. The proposed algorithm may be employed for automated
quantitative morphological analysis of in-stent neointimal hyperplasia.
PMID- 28517653
TI - SU-E-I-101: Initial Implementation and Evaluation of AAPM TG-150 Draft Image
Receptor Non-Uniformity Testing Recommendations.
AB - PURPOSE: To implement in software the procedures described in AAPM Task Group
150's draft recommendations for image receptor performance testing, and to
evaluate the effectiveness and practicality of these procedures. METHODS: Images
of flat fields were acquired using digital x-ray image receptors at 6 cooperating
institutions. Four flat field images obtained with each detector spanned a range
of input detector air kerma. Software based on AAPM TG150's draft report
processed the test images and generated results. Image receptor response and
several measures of non-uniformity were evaluated. Images were divided into 10 mm
square regions, after eliminating 10 mm borders. For each region, signal (mean),
noise (standard deviation) and SNR were calculated. Characteristic signal, noise
and SNR were calculated based on average values from all regions. Local non
uniformity for signal (SLN), noise (NLN) and SNR (SNRLN) were expressed as the
maximum ratio of the absolute difference between each region's value and its 4
nearest neighbors, to the respective characteristic value. Global non-uniformity
(SGN, NGN, SNRGN) were expressed similarly but differences between maximum and
minimum values obtained from the regions were used (without comparison to local
neighbors). RESULTS: TG150 tests discriminated between good and poorly performing
detectors. Improper detector calibration was detectable, with noise non
uniformity proving to be a more sensitive measure than signal or SNR non
uniformity. Detector rotation relative to calibration conditions produced a
greater change in signal non-uniformity than the other measures. Image receptor
structured noise was characterized by an increase in noise non-uniformity with
incident air kerma. CONCLUSIONS: AAPM TG150's proposed approach to image receptor
testing was implemented and evaluated. The approach appears to be an effective
and practical one for routine quality assurance testing of digital radiographic
image receptors.
PMID- 28517654
TI - SU-E-I-68: The Effect of Partially Parallel Imaging on SNR Across Scanning
Platforms.
AB - PURPOSE: Different manufacturers implement partially parallel imaging (PPI) with
different proprietary reconstruction methods and algorithms. Additionally, signal
to noise ratio (SNR) associated with PPI is highly dependent on coil design and
conformation, as quantified by the g-factor. This potentially leads to
differences in SNR across coils and scanners. This study seeks to characterize
the impact of PPI on SNR across four MRI platforms. METHODS: Turbo spin echo
(TSE) scans of a spherical phantom filled with an aqueous solution were acquired
in a head coil on a 3T Siemens Tim Trio, 3T Philips Achieva, 1.5T Toshiba Vantage
and 3T GE Signa Excite HD. Scans at each available integer R-value and
reconstruction method were taken on each scanner. SNR was measured in each image
using the difference method. SNR was normalized to a maximum value of 1.0 for
each reconstruction method. Linear regressions and percent change in SNR relative
to R-value were determined for each reconstruction method. Coefficient of
variation (CV) was used to determine the relationship between PPI
implementations. RESULTS: Slopes of the linear regressions ranged from *0.24 to
*0.27. Percent SNR on average was 67.3%+/-3.7%, 43.3%+/-2.9% and 27.4%+/-6.9% of
the associated non-PPI scan at R=2, 3 and 4 respectively. The range of percent
SNR relative to non-PPI scans was 62.1%-71.7%, 39.8%-46.8% and 20.7%-34.5% at
R=2, 3 and 4 respectively. The CV was 7.75% at R=2, 16.05% at R=3 and 21.79% at
R=4. CONCLUSIONS: Slopes of the linear regressions ranged from -0.24 to -0.27.
Percent SNR on average was 67.3%+/-3.7%, 43.3%+/-2.9% and 27.4%+/-6.9% of the
associated non-PPI scan at R=2, 3 and 4 respectively. The range of percent SNR
relative to non-PPI scans was 62.1%-71.7%, 39.8%-46.8% and 20.7%-34.5% at R=2, 3
and 4 respectively. The CV was 7.75% at R=2, 16.05% at R=3 and 21.79% at R=4.
PMID- 28517655
TI - SU-E-I-112: Pre-Clinical Imaging with an Ultra-High Resolution X-Ray Detector.
AB - PURPOSE: To explore the possible applications for a newly developed ultra-high
resolution, small field-of-view (FOV) micro-solid state x-ray image intensifier
(micro-SSXII) detector. METHODS: The micro-SSXII is based on an 8 micron, 1004 by
1002 electron-multiplying CCD (EMCCD) optically coupled to a 100-micron thick
CsI(Tl) phosphor through a fiber optic window resulting in a FOV of 8 mm with a
resolution limit of more than 20 lp/mm. The system has the capability of
providing real-time images at low exposures because of the high variable gain of
the EMCCD. Several phantoms were prepared by filling catheter tubes of 470 micron
internal diameter with separate mixtures of a casting resin with different ratios
of three different contrast agents (Omnipaque 350, barium sulphate, tantalum
powder). These were imaged with the micro-SSXII at 50 kVp to help select the best
mixture for use in making a cast of a rat kidney whose vasculature would then be
made radiopaque and visualized. RESULTS: The images of all phantoms showed
clumping of these contrast agents within the resin resulting in a non-uniform
mix. The image of the phantom filled with Omnipaque and resin in a 1:4 ratio
showed the best mixture although large bubble formation of the iodine was
observed. This combination was used to make a cast of a rat kidney vasculature
and imaged with the micro-SSXII. Small iodine bubbles with diameters as small as
25 microns were clearly delineated in the rat kidney vessels confirming the sharp
detail capability of the micro-SSXII. CONCLUSIONS: The micro-SSXII in combination
with a soft x-ray spectrum can provide excellent images of small animal casts
prepared with an appropriate radiopaque resin to study finer details of the
vasculature. This new imager has the potential to be used for region-of-interest
x-ray image guidance for interventional studies in small animals. Supported in
part by: NIH Grants R01-EB008425, R01-EB002873 and an equipment grant from
Toshiba Medical Systems Corp.
PMID- 28517656
TI - SU-E-I-78: Neuromelanin in the Subthalamic Nucleus of Patients with Parkinson's
Disease: An Electron Spin Resonance Spectroscopy Study.
AB - PURPOSE: Parkinson disease and related syndromes are associated directly with the
concentrations of neuromelanin, iron and other heavy metals, and nowadays it is
discussed the possible protective role of neuromelanin by the sequester redox
active iron ions, reducing the formation of free hydroxyl radicals and therefore
inactivating the iron ions that induce oxidative stress. The aim of this work is
to study the concentration ratios between iron ions and neuromelanin in
subthalamic nucleus of patients with Parkinson's disease (PD) using Electron Spin
Resonance (ESR). METHODS: Necropsy samples of subthalamic nucleus from eight
human brains were studied: three non-affected by any neurodegenerative disease
and five with Parkinson's disease. The samples were stored in formaldehyde and
washed with a solution of 0.01 molar of ethylenediaminetetraacetic acid. ESR
experiments were development in a JEOL FA-200 X-Band spectrometer at different
temperatures between -170 degrees C to room temperature. The relative
concentrations of each species were estimated from the double integral values of
the fitted spectra. RESULTS: For all samples, ESR spectra showed to be composed
of three different signals following the Curie's law. One signal was attributed
to high-spin ferric ions (g~ 4.3) in rhomboedric symmetry, Cu(II) ions (close to
g=2.0) and neuromelanin (g~ 2.01). The ferric ions concentration ratio between
patients and controls was 3.0+/-0.2. The same ratio for neuromelanine was 0.24+/
0.06. CONCLUSIONS: Our preliminary results indicated a significant increment of
iron concentration in PD samples which agrees with previous histochemical and
biochemical reports. This finding and the clear reduction of neuromelanin
concentration in PD samples suggest the possible role of neuromelanin as iron
ions storage.
PMID- 28517657
TI - SU-E-I-61: Phantom Design for Phase Contrast Breast Imaging.
AB - PURPOSE: Phase contrast breast imaging has the potential to improve visualization
of anatomic structures. While the physics is well-understood, there are several
choices for implementation. In order to evaluate these choices, it is essential
to design a phantom for phase contrast imaging with appropriate breast-equivalent
materials. METHODS: Phantoms for mammography use materials that mimic the x-ray
attenuation properties of breast tissue. Hence, the refractive index decrement
(delta) was determined for breast tissues of varying glandular fraction
[Hammerstein, Radiology 130(2):485-91, 1979] for the energy range (5-100 KeV)
relevant to mammography and breast CT using XOP software (Version 2.3, ESRF,
France) and compared to that of commonly used phantom materials. Delta for 50%
and 70% glandular breast-equivalent material (CIRS Inc., Norfolk, VA), solid
water, BR-12, polymethyl methacrylate (PMMA), beeswax (C46H92O2, density: 0.97
g/cm3 ) and paraffin wax (C25H52, density: 0.95 g/cm3 ) were determined.
Microcalcifications in vivo are either of oxalate or phosphate composition. Delta
of calcium oxalate monohydrate (COM) and calcium hydroxyapatite (CH) were
determined and compared with that of calcium carbonate, gold and aluminum.
RESULTS: In terms of delta, paraffin wax (4% higher) and beeswax (4% higher) best
simulated 50% and 100% glandular breast, respectively. Delta of other commonly
used phantom materials such as 50% and 70% glandular breast-equivalent material,
solid water, and BR-12 were two orders of magnitude higher, and that of PMMA was
28% higher, than 50% glandular breast tissue. For microcalcifications, delta of
gold was 4.6 to 6.5 times higher than that of COM and CH, respectively. Delta of
aluminum and calcium carbonate were found to straddle that of COM and CH.
CONCLUSIONS: For phase contrast imaging, a phantom comprising paraffin wax to
simulate 50% glandular background tissue, beeswax to simulate a mass equivalent
to 100% glandular tissue, and calcium carbonate or aluminum to simulate
microcalcifications is appropriate. Supported in part by the National Institutes
of Health (NIH) grants R01 CA128906 and R21 CA134129. The contents are solely the
responsibility of the authors and do not represent the official views of the NIH
or NCI.
PMID- 28517658
TI - SU-E-I-71: Susceptibility Weighted Imaging (SWI) Software for Post-Processing of
SWI Data.
AB - PURPOSE: To develop open source software for post processing of susceptibility
weighted (SWI) MR images using magnitude and phase data. METHODS: SWI data was
acquired using Philips MRI 3T scanner with the following parameter: 3D T1 FFE
axial with TR=40ms, TE=25ms, FOV=22 cm, acquisition matrix of 440*440 and 40
slices. Both magnitude and phase data was stored for SWI post processing. The SWI
homodyne filtering is performed by converting the magnitude and phase image to
complex real and imaginary images. The SWI software was implemented in C++ using
ITK (Image registration and segmentation toolkit) toolkit. To generate SWI maps
the user needs to provide the DICOM data directory, the series number of DICOM
SWI series, low pass filter size and the weighting factor of phase mask. This
outputted SWI series is saved as DICOM and appended to the patient series and can
be viewed in any DICOM compatible viewer. The software also outputs SWI filtered
phase maps which can be further used for iron quantification in organs like
brain, liver etc. RESULTS: An open source implementation of SWI post-processing
tool using ITK was provided. The SWI processed phase weighted data can be used
for qualitative assessment of iron deposits. The filtered phase map outputted can
be used for quantitative iron measurements. CONCLUSIONS: SWI post processing
software is implemented here to provide qualitative SWI maps of iron deposits in
brain and other organs. The post processed images can also be useful for MR
Venography with minimum intensity projection. This tool would be useful to study
disease processes involved with accumulation of iron in different organs.
PMID- 28517659
TI - SU-E-I-82: Image Signal-To-Noise Equalization in Whole Body PET Using Variable
Acquisition Times.
AB - PURPOSE: Whole Body PET scans are acquired at multiple axial positions, where the
acquisition time at each position is constant. Although the acquisition time is
adjusted for patient weight, the varying amount of attenuation and activity
distribution for different sections, the image S/N can vary significantly. The
aim of this work is to investigate the use of variable bed position scan times in
WB-PET to equalize the Signal-to-Noise ratio in the axial direction. METHODS:
Simulations of activity and attenuation distributions based on whole body CT
scans were performed. Phantoms of different cross sections were also simulated
and imaged. Image noise was estimated by generating multiple noise replicates by
adding Poisson noise to the emission sinograms for the simulated images, and
using a bootstrap method for the phantom patient measurements. By comparing the
square of image noise (SD/Mean) for all the image slices, the acquisition time
for each section could be adjusted to yield uniform image noise for all slices.
The image noise was also compared to the average AC factors through the center of
each body slice. RESULTS: A polynomial function was found for both simulations
and the measurements to accurately describe image noise as a function of AC
factors. Using this relationship, the acquisition time at each axial position can
be adjusted to produce images of relatively uniform S/N, independent of cross
sectional thickness. This was confirmed in phantom and patient data. CONCLUSIONS:
The noise properties of WB-PET images can be equalized axially by adjusting the
acquisition time according to the amount of attenuation. The acquisition time can
be reduced in areas of lower attenuation and increased in more absorbing sections
Since there is a correlation of the image noise and the CT-derived AC factors,
the acquisition times can quickly calculated using a simple functional
relationship.
PMID- 28517661
TI - SU-E-I-114: Clinical Ultrasound Transducer Degradation Effects on the Accuracy of
Spectral Doppler Velocity Measurements.
AB - PURPOSE: Ultrasound Doppler velocity measurements are routinely used to determine
the severity of a stenosis in the carotid, renal or peripheral arteries. The
objective of this study is to investigate and demonstrate the relationship
between Doppler velocity measurements and transducer degradation conditions
encountered in a clinical environment. METHODS: Assessing transducer performance
was accomplished using the First Call aPerio Test System transducer analyzer
(Sonora Medical Systems, Longmont, CO). This system was used to conduct 1,145
semi-annual transducer assessments at 7 clinical sites from September 2007 to
February 2012 as part of a comprehensive quality control program. The results
were evaluated to determine the degree of transducer degradation encountered in
the clinical environment. A Siemens Acuson S2000 (Siemens AG, Erlangen, Germany)
ultrasound system was employed with the 1425A LE Doppler Flow System (Gammex,
Middleton, WI) to determine Doppler velocity measurements. A transducer fixation
device was fabricated to provide accurate, repeatable velocity measurements.
Transducers with the most severe degradation were evaluated by comparing velocity
measurements to those without defects. Using several matched transducer pairs,
simulated failure modes were tested. The Doppler measured time-average mean
(TAMn) and time-average maximum (TAMx) velocities were obtained and reported.
RESULTS: This investigation found that 4.5% of the transducers surveyed during
this 5-year period of time failed at least one acceptance criteria. Many (346 or
30%) had at least one defect. Typical findings include dead elements, lens
delamination, wire cuts, and capacitance shorts. Only the most severe transducer
defects and degradation conditions resulted in a noticeable deviation in the
velocity measurements. Simulated transducer degradation testing confirmed this
finding. CONCLUSIONS: The relationship between Doppler velocity measurements and
transducer degradation conditions is limited, becoming significant for only the
most severe degradation conditions. Based on our experience, this level of
transducer degradation is rarely encountered in the clinical environment.
PMID- 28517662
TI - SU-E-I-85: Evaluation of a Solid-State Dosimeter Module for Measuring Nuclear
Medicine Radionuclides.
AB - PURPOSE: A recently introduced solid-state dosimeter module (UDOS001, Teledyne
Microelectronic Technologies, Los Angeles, CA) requires only external power
(e.g., from two nine-volt batteries in series) and a battery- powered data
recorder to assemble a compact, portable dosimeter. This device was developed for
radiation detection and monitoring of a wide range of radiation types. It has a
nominal minimum energy of 100 keV. The present study sought to determine its
suitability for measuring the dose from radionuclides used in nuclear medicine.
METHODS: Three radionuclides (initially 4.77 mCi of F-18, 3.86 mCi of I-131, and
12.4 mCi of Tc-99m) were measured at a distance of one meter and at several
different angles of incidence. The most sensitive analog output of the dosimeter
was digitized by a battery-powered data logging device (Track-It 5VDC, Monarch
Instrument, Amherst NH). These data were transferred from the data logger into a
Windows 7 personal computer, formatted as an Excel 2010 spreadsheet and converted
from voltage to dose using the manufacturer's nominal calibration factor of 14
urad/19.5 mV step. The dose rate was determined from the slope of a linear fit to
the cumulated dose as a function of time. RESULTS: The nominal calibration of the
dosimeter gives dose rate measurements that are close to published gamma ray dose
rate constants for these radionuclides (0.65 vs. 0.70, 0.25 vs. 0.28, and 0.071
vs. 0.078 mrad/mCi-hr respectively). The angular dependence of the response is
greater at 140 keV than at 511 keV, but an acceptance angle of at least 90
degrees has uniform response with all three radionuclides. CONCLUSIONS: A better
calibration factor would be 0.154 urad/19.5 mV step at these gamma ray energies.
This dosimeter can be used to measure the dose from common radionuclides used in
nuclear medicine.
PMID- 28517660
TI - SU-E-I-103: Detecting Anomalous Pixels and Correlated Artifacts in Digital
Detectors from Flat-Field Images.
AB - PURPOSE: Anomalous pixels may be defined as those pixels whose exposure response
relationship is deviant from the typical, expected or calibrated response. A
group of anomalous pixels may Result in visible correlated artifacts. Here we
demonstrate an approach to identify anomalous pixels and correlated artifacts
using flat-field images. METHODS: Using manufacturer specific calibration
geometry, sets of four flat-field images per detector were obtained with varying
input air kerma values (0.5 to 160 MUGy) from 9 digital detectors at 6
institutions. Images obtained before and after calibration, with both proper and
improper gain maps and structured artifacts were additionally acquired with some
detectors. Image analysis methodology under consideration by AAPM Task Group 150
was used.After eliminating 10mm borders, images were divided into square regions
(100mm2 ). Anomalous pixels were identified as pixels within each region with
valuesabove or below +/-3 standard deviations (SD) relative to the mean value of
the region. If these pixels were identified in all four images comprising a set,
then they were reported as anomalous. Line artifacts were identified as rows and
columns with cumulative profile values that were above or below +/-3 SD with
respect to the mean value of neighboring profiles in the set of four flat-field
mages. Results were verified with visual inspection of the images. RESULTS: For
four sets of images, the algorithm did not identify any anomalous pixels, and
none were spotted on visible inspection as well, while for five sets of images
the identified anomalous pixels matched visual inspection results. Anomalous
pixel detection failed in regions with an unusually large number of defects and
structured noise, since those regions exhibited relatively large SD. Line
artifacts consistent with visual analysis were identified correctly when present.
CONCLUSIONS: A practical approach to identify anomalous pixels and correlated
artifacts from flat-field images is demonstrated.
PMID- 28517664
TI - SU-E-I-107: Suitability of Various Radiation Detectors Used in Radiation Therapy
for X-Ray Dosimetry in Computed Tomography.
AB - PURPOSE: Assessment of suitability for X-ray dosimetry in computed tomography of
various ionization chambers, diodes and two-dimensional detector arrays primarily
used in radiation therapy. METHODS: An Oldelft X-ray simulation unit was used to
irradiate PTW 60008, 60012 dosimetry diodes, PTW 23332, 31013, 31010, 31006 axial
symmetrical ionization chambers, PTW 23343, 34001 plane parallel ionization
chambers and PTW Starcheck and 2D-Array seven29 as well as a prototype Farmer
chamber with a copper wall. Peak potential was varied from 50 kV up to 125 kV and
beam qualities were quantified through half-value-layer measurements. Energy
response was investigated free in air as well as in 2 cm depth in a solid water
phantom and refers to a manufacturer calibrated PTW 60004 diode for kV-dosimetry.
RESULTS: The thimble ionization chambers PTW 31010, 31013, the uncapsuled diode
PTW 60012 and the PTW 2D-Array seven29 exhibit an energy response deviation in
the investigated energy region of approximately 10% or lower thus proving good
usability in X-ray dosimetry if higher spatial resolution is needed or rotational
irradiations occur. CONCLUSIONS: It could be shown that in radiation therapy
routinely used detectors are usable in a much lower energy region. The rotational
symmetry is of advantage in computed tomography dosimetry and enables dose
profile as well as point dose measurements in a suitable phantom for estimation
of organ doses. Additional the PTW 2D-Array seven29 can give a quick overview of
radiation fields in non-rotating tasks.
PMID- 28517663
TI - SU-E-I-96: Realistic Synthetic CT Imaging of Small Numerical Lesions with Simple
CT Simulation Model Incorporating Equipment MTF.
AB - PURPOSE: Quantitative analysis in CT imaging often requires image data set of
lesions with ground truth, which is practically impossible in general. This study
presents a simple CT simulation model which enables to create realistic synthetic
CT images of numerical voxel phantoms for small lesionswith various shape and
sizes. METHODS: Basic CT parameters were acquired from DICOM header of target CT
data, and were used in the CT simulator. Frequency response of forward and
backward projectors were determined by measuring NPS of reconstructed image from
white Gaussian noise input data, which were then used to iteratively calibrate
those projectors so as to produce white Gaussian NPS output. Then, the MTF of
target equipment were measured and incorporated into the sinogram filter before
back projection in order to reflect focal spot blurring and vendor specific recon
kernel. For validation, physical and numerical phantoms with rod and tube shape
of 2mm ~ 10mm were created and imaged with a real CT (Sensation 16, Siemens) and
the proposed simulated CT, respectively. Images were reconstructed with 8
different kernels (B10 ~ B80) in both CT imaging technique, and their line
profiles were compared. RESULTS: Synthesized and physically scanned CT images of
phantoms with different shape, sizes, and recon kernels agreed well in visual
assessment, size measurement, and line profile comparison. CONCLUSION: Proposed
method could produce realistic synthetic CT images of numerical phantoms highly
mimicking in visual appearance and quantitative comparison, which has a potential
for use as ground truth data set in quantitative image analysis.
PMID- 28517666
TI - SU-E-I-89: Applying Image Gently and Image Wisely in Nuclear Medicine.
AB - PURPOSE: To demonstrate how principles and recommendations of the Image Gently(r)
and Image WiselyTM campaigns can be clinically implemented. METHODS:
Implementation of Image Gently(r) and Image WiselyTM guidelines was a quality and
safety improvement project for our Nuclear Medicine department in 2011. Pediatric
administered radiopharmaceutical doses were compared to recommended doses in the
North American Consensus Guidelines for AdministeredRadiopharmaceutical
Activities in Children and Adolescents and the European Association of Nuclear
Medicine Paediatric Dose Card. Adult administered radiopharmaceutical doses were
compared to administered doses in NCRP Report No. 160 and IAEA Report No. 40.
RESULTS: Evaluation of site administered radiopharmaceutical doses showed that
nearly all doses were comparable to those recommended by national and
international advisory bodies. Administered doses for the pediatric renogram and
the adult gastric emptying were adjusted to match the recommendations and
resultant image quality evaluated. CONCLUSIONS: Radiation dose from nuclear
medicine procedures should not be overlooked in the focus on CT dose reduction.
An estimated 19.7 million nuclear medicine procedures are done annually in the
U.S., with doses comparable to that from CT scans. Nuclear medicine departments
should evaluate their pediatric administeredradiopharmaceutical doses against the
North American Consensus Guidelines for Administered Radiopharmaceutical
Activities in Children and Adolescents and evaluate their adult doses against
national and international standards. Administered doses that are not comparable
to the recommended values should be adjusted accordingly. Additional steps to
reduce patient radiation dose include decision support to reduce inappropriate
ordering, technique optimization for the CT scan portion of SPECT/CT and PET/CT,
use of vendor's dose reduction camera and software technology, use of shorter
lived radiopharmaceuticals, and 'right sizing' patient doses by weight.
PMID- 28517665
TI - SU-E-I-73: Gray Matter Atrophy and White Matter Tract Abnormalities by Voxel Wise
Correlation Analysis in Patients with Alzheimer's Disease.
AB - PURPOSE: We evaluated the relationship between white matter (WM) tract
disintegration and gray matter (GM) atrophy in patients with Alzheimer's disease
(AD), mild cognitive impairment (MCI) and controls, using diffusion tensor
imaging (DTI) and an optimized voxel-based analysis. METHODS: Two hundred thirty
one individuals (61 controls, 116 MCI and 54 AD) were included. Voxel-based WM
tract statistics was used to obtain whole-brain maps of WM bundles for FA. Voxel
based morphometry (VBM) was conducted to detect regions of gray matter (GM)
atrophy in the AD, MCI group relative to the control group. FA maps were
processed to make voxel-wise comparison of tract based analysis in whole brain
between each the two groups. The relationship between locations of abnormalities
in the WM and GM were examined. RESULTS: Patients with AD showed significant GM
atrophy in posterior cingulate gyrus (BA31, 32) to the precuneus, the middle
temporal lobe (BA19), the superior frontal (BA9) to the anterior cingulate (BA
32), the medial frontal lobe (BA 11, BA25), the hippocampus, the parahippocampal
gyrus (BA30/34) and the insula, and WM tract disintegrity of the uncinate
fasciculus, posterior cingulate fasciculus and fornix compared with the control
and MCI groups. These abnormalities in the AD group were caused by either
structural changes in GM atrophy or neural dysfunction due to functional
disconnections in the WM tract. CONCLUSIONS: The GM atrophy resulting from WM
tract disintegration or GM atrophy itself may be the first step in the AD
process, resulting in anatomically congruent correlations between WM
disintegration and regional GM atrophy. Using tract based spatial statistics and
voxel based analysis, both of which are useful in investigating GM and WM changes
in individuals with neurodegenerative disorders.
PMID- 28517667
TI - SU-E-I-100: Feasibility Study of Gamma-Ray Medical Radiography.
AB - PURPOSE: The purpose of this research is to study an alternative technique to
conventional x-ray radiography that requires less patient radiation dose, less
cost, portable, requires less maintenance, and less power consumption. This
research explores the feasibility of using gamma-ray radiography in medical
imaging. Gamma-ray medical radiography has the potential to provide alternative
diagnostic medical information to X-ray radiography. METHODS: Approximately one
Ci of Am-241 radioactive source which emits monoenergetic 59.5 KeV gamma rays was
used in this study. Several factors that influence this feasibility were studied.
These were the radiation source uniformity, image uniformity, image quality
parameters such as contrast, noise, and spatial resolution. In addition, visual
assessment of several human phantom gamma-ray and x-ray images were conducted.
The images were recorded on computed radiography image receptors and displayed on
a standard monitor. RESULTS: The radioactive source provided a relatively uniform
radiation exposure and uniform images. Image noise was mainly dependent on the
exposure time and the source size. Although the contrast depended on the window
and level setting, it was also dependent on the exposure time and the source
size. Spatial resolution was dependent on the source size and the magnification.
The generated gamma-ray images were of lower quality than the X-ray images which
was mainly due to the low radioactivity used. However, the gamma-ray images
displayed most of the main structures contained in the humanoid phantoms.
CONCLUSIONS: Thisresearch explored the feasibility of using gamma-ray radiography
in medical imaging and showed that gamma-ray medical radiography has the
potential to provide alternative diagnostic medical information to X-ray
radiography. Finally, this research also paves the way for the usage and
production of high radioactive Am-241 source that will show high quality medical
gamma-ray radiography is feasible.
PMID- 28517669
TI - SU-E-I-111: Evaluation of the Analytical Scattering Models of 1) Lynch-Dahl 2)
Highland and 3) Rossi for Proton Beams and Comparison with GEANT4 Monte Carlo
Simulations as a Prerequisite for Proton Radiography Applications for Patients.
AB - PURPOSE: To evaluate the approximate 1) Lynch-Dahl 2) Highland and 3) Rossi
scattering models for proton beams with GEANT4 Monte Carlo. This is a
prerequisite for proton radiography applications for patients. METHODS: A Matlab
program developed in-house at MGH was used to obtain a semianalytical generalized
Fermi-Eyges theory estimation of the spatial and angular spreads of a 230 MeV
zero-spread incident proton beam as a function of depth. The constants of 1)
Lynch-Dahl 2) Highland and 3) Rossi were used respectively for each model. MC
simulations will determine which approximation provides the best prediction for
different media configurations. Further, the calculated spreads were used to
inform proton radiography imaging by calculating two limiting angles, a
positional Acut and a directional Ccut. Acut is defined as the viewing angle of a
point of incidence observer at which they see a point displaced by one positional
standard deviation. Ccut is defined as the direction cosine of one angular
standard deviation momenta. RESULTS: Both the angular and spatial spreads as well
as their respective model differences rose monotonically with depth in water. At
30 cm depth the angular spread reached values around 3 degrees with about 0.32
degrees model difference, translating to Ccut differences in the first or second
significant digit. At the same depth the spatial spread reached values around 1.2
cm with about 0.7 mm model difference, translating to Acut differences in the
first or second significant digit. Preliminary MC data (not shown) indicate that
the signals obtained due to the influence of inhomogeneities are small and the
model differences may be relevant. CONCLUSIONS: We observed non-negligible
differences between the models using MC. Further analysis is required to
understand, which model provides most accurate scattering predictions for protons
penetrating different media configurations.
PMID- 28517668
TI - SU-E-I-67: Multi-Shot RESOLVE Compared to Single-Shot EPI Diffusion- Weighted MR
Imaging Acquisition Scheme.
AB - PURPOSE: The purpose of this project was to configure the parameters for optimal
comparison of image quality differences between the prototype imaging technique,
read-out-segmented EPI multi-shot (RESOLVE) and the clinically used single-shot
EPI (SS-EPI) MRI sequence for Diffusion Weighted Imaging (DWI) in a saline
phantom, followed by a normal rat brain. METHODS: Saline phantom (4.2 * 4.2 cm2 )
and a rat brain were imaged on the 1.5T ESPREE (Siemens, Germany) MRI magnet
using a wrist coil. Both the SS-EPI and RESOLVE DWI were optimized with equal
imaging parameters such as slice thickness/slice gap = 3.0/0 mm, field of view =
210 mm, phase resolution = 100%, and diffusion b values = 0, 600 s/mm2 while
other parameters were given similar settings such as the base resolution, which
had to be interpolated for the SS-EPI to 96i to match the RESOLVE as it was
unable to be set at 192. Image quality was compared in terms of signal intensity,
distortion, % ghosting and Apparent Diffusion Co-efficient (ADC) measurements
from each sequence. RESULTS: A marked enhancement of overall image quality with
superior detail was observed in each of the scans from the RESOLVE sequence when
compared to the SS-EPI. Comparing the efficiency of both sequences in terms of
image quality, RESOLVE demonstrated a better stable image with minimal distortion
and ghosting. The phantom dimensions obtained from RESOLVE images matched the
actual dimensions perfectly. RESOLVE images had signal intensities significantly
higher than (2.4*) the SS-EPI images (p=0.0008) and ~0.6 % times less ghosting
compared to SS-EPI (p=0.82) which also exhibited distortion with reduced phantom
dimensions (4.05 * 3.28 cm) from original. The ADC values computed were almost
identical to be (p=0.32) from SS-EPI (2.21mm2 /sec) and RESOLVE (2.19mm2 /sec).
CONCLUSIONS: The RESOLVE sequence has significantly superior image quality
compared to SS-EPI at 1.5 T with reasonable scan times. DWI with RESLOVE
acquisition scheme can be highly beneficial in obtaining distortion free images
in routine clinical studies to characterize tumors and other pathological
mechanisms with much greater detail than the current clinically used SS-EPI.
PMID- 28517670
TI - SU-E-I-77: X-Ray Coherent Scatter Diffraction Pattern Modeling in GEANT4.
AB - PURPOSE: To model X-ray coherent scatter diffraction patterns in GEANT4 for
simulating experiments involving material detection through diffraction pattern
measurement. Although coherent scatter cross-sections are modeled accurately in
GEANT4, diffraction patterns for crystalline materials are not yet included. Here
we describe our modeling of crystalline diffraction patterns in GEANT4 for
specific materials and the validation of the results against experimentally
measured data. METHODS: Coherent scatter in GEANT4 is currently based on
Hubbell's non-relativistic form factor tabulations from EPDL97. We modified the
form-factors by introducing an interference function that accounts for the
angular dependence between the Rayleigh-scattered photons and the photon
wavelength. The modified form factors were used to replace the inherent form
factors in GEANT4. The simulation was tested using monochromatic and
polychromatic x-ray beams (separately) incident on objects containing one or more
elements with modified form-factors. The simulation results were compared against
the experimentally measured diffraction images of corresponding objects using an
in-house x-ray diffraction imager for validation. The comparison was made using
the following metrics: number of diffraction rings, radial distance, absolute
intensity, and relative intensity. RESULTS: Sharp diffraction pattern rings were
observed in the monochromatic simulations at locations consistent with the
angular dependence of the photon wavelength. In the polychromatic simulations,
the diffraction patterns exhibited a radial blur consistent with the energy
spread of the polychromatic spectrum. The simulated and experimentally measured
patterns showed identical numbers of rings with close agreement in radial
distance, absolute and relative intensities (barring statistical fluctuations).
No significant change was observed in the execution time of the simulations.
CONCLUSIONS: This work demonstrates the ability to model coherent scatter
diffraction in GEANT4 in an accurate and efficient manner without compromising
the accuracy or runtime of the simulation. This work was supported by the
Department of Homeland Security under grant DHS (BAA 10-01 F075), and by the
Department of Defense under award W81XWH-09-1-0066.
PMID- 28517671
TI - SU-E-I-60: Validation of An Optically Stimulated Luminescent (OSL) Dosimeter for
Use in Output Exposure Control Verification of Mammography Imaging Systems.
AB - PURPOSE: To develop and validate an Optically Stimulated Luminescent (OSL)
dosimeter for exposure control verification of x-ray projection mammography
imaging systems. METHODS: The active detection element of the dosimeter is a
strip of OSL material 3.0 mm wide, 0.13 mm thick and 30.0 mm long with an
overlying aluminum step wedge with thicknesses of 0, 0.2, 0.4 and 0.6 mm Al,
encapsulated in a light-tight plastic enclosure with outer dimensions of 10.0 mm
wide, 5.4 mm thick, and 54.0 mm long. The dosimeter is used in conjunction with a
breast phantom for the purpose of estimating the half-value layer (HVL), entrance
surface exposure (ESE), and average glandular dose (AGD) in conventional
projection mammography. ESE and HVL were computed based on analysis of exposure
profiles obtained from exposed strip dosimeters. The AGD was estimated by
multiplying the ESE by the appropriate exposure to dose conversion factor for the
thickness and % glandular tissue fraction represented by the phantom and target
filter combination employed. The accuracy and reproducibility of the ESE, HVL and
AGD estimates obtained using the dosimeter positioned on the surface of the ACR
phantom at the chest wall edge, was evaluated using mammography systems utilizing
different imaging receptor technology, i.e. screen-film (SF), computed
radiography (CR) and direct radiography (DR) and compared against results
obtained using a calibrated ion chamber fitted with a mammography probe. RESULTS:
ESE, AGD and HVL results obtained using the OSL mammography QA dosimeter agreed
with results obtained using an ion chamber to within 5-10%, depending on the
target-filter combination used. Repeat readings were highly consistent with a
coefficient of variation = 5%. CONCLUSIONS: The OSL mammography QA dosimeter has
been shown to effectively estimate ESE, HVL and AGD, demonstrating its usefulness
for secondary monitoring of output exposure of mammography imaging systems.
PMID- 28517672
TI - SU-E-I-81: Toward in Vivo Magnetic Spectroscopy of Brownian Motion.
AB - PURPOSE: Magnetic spectroscopy of Brownian motion (MSB) has been used previously
to measure temperature, viscosity, and cellular binding in vitro. The MSB signal
a ratio of the 5th to 3rd harmonic of the response from magnetic nanoparticles
to an oscillating field - provides insight into particle microenvironment. These
biosensing capabilities would be productive in vivo but until now were prevented
by sensitivity limits. Our goal was to design and create a similar apparatus for
work in vivo. In vivo spectroscopy is a viable precursor to imaging, and is
essential for drug delivery or therapeutic methods like hyperthermia. METHODS:
Coil geometries were modeled to optimize a uniform Helmholtz drive coil and
imaging coil with maximal spatial resolution. The completed apparatus includes
balancing and trim coils to zero out unwanted background fields. The coils were
characterized and experiments were performed to verify consistency with previous
in vitro experiments. Finally, as an in vivo experiment, we took MSB spectra on
living mice with five week old melanomas injected with 200ug of 100nm starch
coated nanoparticles. RESULTS: The drive coil is capable of sustaining 12.5mT
fields up to 1.5kHz with a field variation of 3% throughout the sample volume.
The pickup coil is frequency independent and has a vertical and horizontal range
of 5mm and 10mm respectively before the MSB signal drops below 50%. The minimum
sensitivity is 50-70MUg of iron. MSB signal response to viscosity changes shows
the same signatures as the in vitro apparatus. The in vivo data showed successful
sensing of nanoparticles. We also saw the MSB signal decay with time showing the
apparatus can detect changes in particle behavior due to interactions with
biology. CONCLUSIONS: We achieved in vivo MSB and due to sufficient sensitivity
we are motivated to further work in monitoring in vivo cellular uptake and
viscosity.
PMID- 28517732
TI - T-cells and macrophages peak weeks after experimental stroke: Spatial and
temporal characteristics.
AB - The activities of the central and peripheral immune systems impact neurological
outcome after ischemic stroke. However, studies investigating the temporal
profile of leukocyte infiltration, especially T-cell recruitment, are sparse. Our
aim was to investigate leukocyte infiltration at different time points after
experimental stroke in mice. Permanent middle cerebral artery occlusion was
performed on 11 weeks old C57BL/6J mice, allowed to survive for 1, 3, 8, 14 or 28
days. In addition to infarct size measurements, detailed immunohistochemical
analyses of T-cell and macrophage influx were performed. A recently introduced F
19 MR probe (V-sense), designed to track macrophages, was furthermore tested.
Fourteen and 28 days after permanent middle cerebral artery occlusion a
significant increase in CD3+ T-cells was found within the ipsilateral hemisphere
compared to controls, especially within the infarct core and the corpus callosum.
The number of CD68+ cells within the infarct core was significantly increased at
days 8, 14 and 28. This temporal pattern was also seen in MRI. After experimental
stroke within the infarcted cortex we found a delayed (day 14) infiltration of T
cells and macrophages. Furthermore, our data show that T-cells are present in
higher numbers in the corpus callosum compared to the rest of the brain (except
from the infarct core where they were highest).
PMID- 28517793
TI - SU-E-T-170: A Viable Approach to Patient Specific QA for Spine VMAT SRS Using
EPID-Based Dosimetry.
AB - PURPOSE: VMAT involves multi-parameter modulations, thus presenting multi
dimensional challenges. Here, we present a viable approach to VMAT patient
specific QA using EPID-based dosimetry for spine VMAT SRS casesMethods: Our spine
VMAT SRS plans consisted of two full arcs and were optimized with 6 MV photons
for a Varian Trilogy LINAC. The QA plans were computed by resetting all control
points to 0 degrees gantry angle while keeping the MLC apertures and
corresponding MU weights intact. The dose distribution at the depth of clinical
significance was calculated in a solid water phantom. EPIDose (Sun Nuclear Corp)
was used to convert MV EPID images into absolute dose in a plane of interest in a
homogeneous medium. During measurements, the source-to-detector distance (SDD)
was set to 105 cm and the VMAT QA plan was delivered with 600 MU/min. For each QA
plan, three measurements were made. The average pass rate (thresholds: 2%/2 mm)
was then calculated. In addition, the dose at the isocenter or other points of
clinical significance was also measured and the mean was calculated. RESULTS: Our
current institutional QA acceptance criteria for VMAT plans are: pass rate 90%
for 2%/2mm with a dose threshold of 10% and the discrepancy between the measured
and planned doses at the isocenter or other points of clinical significance 2%.
Our preliminary investigation indicated that the pass rate was normally greater
than 95.0% with a total number of valid detection points of ~30000. The dose
difference at the point of interest was, in general, around +/-1.0 %. Sharp dose
gradients were accurately detected at the PTV-cord interface. CONCLUSIONS: EPID-
based dosimetry is real-time and financially viable. It can achieve sub-
millimeter dosimetry accuracy without extensive inter-diode interpolations. We
believe that EPID-based VMAT dosimetry offers a competitive alternative to other
competing dosimetry technologies.
PMID- 28517794
TI - SU-E-T-180: The Radiological Physics Center's Anthropomorphic Quality Assurance
Phantom Program.
AB - PURPOSE: To describe the phantoms, program logistics and current results for the
Radiological Physics Center's (RPC) anthropomorphic QA phantom program for
credentialing institutions for participation in NCI-sponsored advanced technology
clinical trials. METHODS: The RPC has developed an extensive phantom
credentialing program consisting of four different phantoms designs: H&N, pelvis,
lung and spine. These QA phantoms are water-filled plastic shells with imageable
targets, avoidance structures, and heterogeneities that contain TLD and
radiochromic film dosimeters. Institutions wishing to be credentialed request a
phantom and are prioritized for delivery. At the institution, the phantom is
imaged, a treatment plan is developed, the phantom is positioned on the treatment
couch and the treatment is delivered. The phantom is returned and the measured
dose distributions are compared to the institution's electronically submitted
treatment plan dosimetry data. RESULTS: The RPC currently has an inventory of 31
H&N, 10 pelvis, 9 lung, and 8 spine phantoms that are mailed to institutions
nationally and internationally. In 2011, 444 of these phantoms were mailed out
for credentialing. Once the phantom is sent, it takes the institution an average
of 26 days to return it to the RPC. On average the dosimeters are analyzed within
17 days and the report is sent 21 days after receipt of the phantom data. In 2011
the percent of phantoms meeting the acceptance criteria increased by 12, 13 and 6
percentage points for the H&N, spine and lung phantoms, respectively. It fell by
5 percentage points for the pelvis phantom. CONCLUSIONS: The RPC's QA phantom
program has been an effective and responsive QA tool for assessing the use of
advanced technologies in NCI sponsored clinical trials. The RPC has been
efficient in its mailing of phantoms, and analyzing and reporting results. Work
supported by PHS grant CA10953 and CA081647 (NCI, DHHS).
PMID- 28517733
TI - Comparison of the measuring efficacy of transepidermal water loss of a reasonably
priced, portable closed-chamber system device H4500 with that of rather
expensive, conventional devices such as Tewameter(r) and Vapometer(r).
AB - BACKGROUND/PURPOSE: Although measuring transepidermal water loss (TEWL) is
important to assess the barrier function of the stratum corneum (SC), the
commercially available instruments are rather expensive. Recently launched Model
H4500 employs a closed-chamber system to measure TEWL and is more reasonably
priced compared to devices currently in general use. METHODS: To check the
reproducibility of the obtained data with H4500, we conducted measurements on the
volar forearms of healthy volunteers and compared these data with those measured
with Vapometer(r) and Tewameter(r) . Then, we checked the correlations between
the TEWL data obtained with these different devices on the same volar forearms of
15 healthy volunteers before and after the artificial production of barrier
damage of the SC by tape stripping or by 0.5% aqueous solution of sodium lauryl
sulfate. RESULTS: The obtained intra-class correlation coefficient (ICC, [1, 1])
with 95% CI of H4500 was 0.927 (0.835-0.978). Namely, an excellent correlation
could be found in the values of TEWL measured with these three different
instruments not only on healthy skin but also on the artificially barrier-damaged
skin. CONCLUSIONS: H4500 is considered to be practical for daily use because of
its performance as well as its reasonable price as compared with conventional
devices.
PMID- 28517795
TI - SU-E-T-172: Ion Recombination Correction Factor in Medium Dose Rate for Advanced
Markus Ionization Chamber.
AB - PURPOSE: To determine the ion recombination correction factor using different
methods in medium dose per pulse electron beams for Advance Markus ionization
chamber (AMC) Methods: Two different methods were applied to obtain ion
recombination correction factor. Conventional Boag's two voltage analysis (TVA)
recommended in IAEA TRS-398 dosimetry protocol and recently modified Boag's TVA
expressions which consider the effect of free electron contribution on ks value.
High energy electron beams of a dedicated linear accelerator, NOCAC7 (NRT,
Italy), for intraoperative radiation therapy were applied. Dose per pulse in
medium range of 4 to 41 mGy/pulse was investigated. Radiochromic films (ISP
Gafchromic EBT2, USA) have been exploited as reference dose rate independent
method. Dose measurement was performed by AMC in a small water phantom (IBA
Dosimetry, Germany). RESULTS: At reference conditions (9 MeV, 100 mm applicator,
SSD 80 cm (27 mGy/pulse)), ks values derived from IAEA TRS- 398 dosimetry
protocols deviates 0.3% from reference value. From 4-35 mGy/pulse TVA yielded
acceptable result (in average 1.0% deviation). For dose rate more that 35
mGy/pulse, conventional two voltage analysis (TVA) might be applied with caution
(4.2% deviation at 41 mGy/pulse). In this range first model in the new modified
Boag's expressions yielded acceptable accordance (average deviation 1.3%) in
comparison with dose rate independent reference dosimeter (EBT2, Gafchromic
film). The deviation in ks value among Boag's modified expressions increased when
the dose rate raised. CONCLUSIONS: Authors concluded that AMC could be employed
for absorbed dose determination of medium dose per pulse electron beams. The
accuracy of TVA which is recommended currently in dosimetry protocol IAEA-TRS-398
is dependent on the range of applied dose rate. It is proper to be used for dose
rate less than 35 mGy/pulse. First expression in Boag's modified formulas is
proper for ks determination in high dose rate values (> 35 mGy/pulse).
PMID- 28517796
TI - SU-E-T-182: Delivery Verification of Tomotherapy Treatments Using Exit Detector
Sinograms: A Phantom Study.
AB - PURPOSE: The objective of this study was to use a liquid water female body
phantom to investigate the feasibility of using helical Tomotherapy's exit
detector data sinograms (EDDS) for quality assurance of Tomotherapy treatments.
METHODS: Delivery Verification software (DV-Tool), described by Kapatoes et al.,
uses EDDS and daily mega-voltage-CT images for delivery sinogram reconstruction
and subsequent dose computations. These dose distributions should reflect
variations in patient's anatomy and machine delivery. Phantom was used to verify
the robustness of the DV-Tool for machine consistency over 2months, and
sensitivity to weight loss and setup errors. Weight loss simulations were done by
removing layers of bolus from the phantom's pelvis. Setup errors were simulated
by performing known table shifts before the treatment. Two treatment plans
simulating a breast and gynecological treatment plans were used for these
evaluations. Reconstructed doses and dose volume histograms (DVHs) were analyzed
in comparison to the plan DVHs by scaling the reconstructed PTV mean dose (PTV
MD) to match the plan. PTV-MD differences before and after machine output
adjustments were evaluated. RESULTS: Machine consistency check of gynecological
plan revealed that the deviations were greater (+/-5%) during the week prior to
target replacement. After output adjustments, the deviations for breast and
gynecological plans agreed within +/-1.0% and +/-2.5%, respectively. Weight loss
on the gynecological plan showed a correlation (R2=0.998) between lost thickness
and increasing PTV-MD by approximately 5%/cm. Setup errors on the breast plan
showed broadening shoulder of the PTV DVH for shifts greater than 5mm. Volume at
20Gy for the right lung increased by 6% for 10mm shifts in both x and z
directions. CONCLUSIONS: The DV-Tool is sensitive to simulated weight loss, setup
errors, and machine output. Exit detector data and the DV-Tool have great
potential for monitoring patient's delivered treatments. However, clinical
workflow needs to be established.
PMID- 28517797
TI - SU-E-T-154: Online Dose Verification with Gafchromic Film for Fixed-Gantry and
Rotational Intensity Modulated Radiation Therapy: A Phantom Study.
AB - PURPOSE: The patient specific quality assurance (QA) measurements for fixed
gantry and rotational intensity modulated radiation therapy (IMRT and
VMAT/RapidArc) are usually performed on a homogeneous phantom prior to the
treatment. The purpose of this study is to develop an online method to verify the
delivered dose to the patient on the treatment day. METHODS: An anthropomorphic
(Rando) head phantom was immobilized in treatment position with a thermoplastic
mask to simulate a real patient. A sheet of gafchromic film (EBT2) was sandwiched
between a 1-cm-thick solid water slab, which was fixed to the Type-S extension
board, and the patient's head hold (a pillow used here). The CT images of the
Rando phantom were acquired and exported to the treatment planning systems. One
step-and-shot fixed-gantry IMRT plan and one RapidArc plan were generated and the
dose distributions on the film plane were calculated. The two plans were
delivered to the patient (Rando phantom in this study) in the treatment position
on a Varian Trilogy linear accelerator with two new films. The films were
scanned, and the measurements were compared with the planned doses. RESULTS: The
composite dose distributions measured on the film plane were the actual delivered
dose for the treatment. The comparison between the measurement and planned dose
profiles shows an agreement within 3% because of the good reproducibility of
phantom positioning. Gamma pass rates (using 3mm and 3% criteria) for the IMRT
and RapidArc plan were found to be 95% and 94%, respectively. CONCLUSIONS: The
phantom study has demonstrated the feasibility of using gafchromic film for
online dose verification. This simple method takes into account the patient
heterogeneity and the treatment associated uncertainties such as setup error,
intrafraction motions and machine related variations. It can be implemented as an
online physics and/or clinical QA tool without taking additional machine time.
PMID- 28517798
TI - SU-E-T-193: Using Truebeam's Research Mode to Automate Mechanical Quality
Assurance.
AB - PURPOSE: To determine the feasibility of automating mechanical quality assurance
measurements on the Varian Truebeam LINAC. METHODS: Using the XML coding
capability of the Varian Truebeam Research Mode, the LINAC was programmed to
mimic the beams delivered for the following mechanical tests. These tests
included: Field size accuracy, jaw positions for asymmetric fields, collimator
rotation isocenter, and MLC positional-accuracy. Images for these beams were
acquired with the EPID. The images were analyzed using an analysis code written
in MATLAB. Tests for gantry and couch rotation isocenters and radiation and
mechanical isocenter coincidence are being developed. RESULTS: For field-sizes
ranging from 4*4cm2 to 15*15cm2 , the measured matched the nominal field sizes to
within 1mm. The collimator rotation isocenter and the overall accuracy for
asymmetric field matched to within 1mm. No positional error >1mm was seen in the
33 MLC pairs visible in the MLC positional-accuracy images. CONCLUSIONS: A large
portion of the time required to make mechanical QA measurements using film is
spent placing, processing, and scanning the film. Complete automation in
performing these mechanical tests results in a significant time gain compared to
film. A majority of the mechanical tests suggested by TG-142 have been performed
using this technique, and an automated mechanical QA process has been established
in our clinic.
PMID- 28517799
TI - SU-E-T-165: Protocol for Simplified Radiochromic Film Dosimetry.
AB - PURPOSE: Radiochromic film provides dose measurement at high spatial resolution,
but often is not selected for routine evaluation of patient-specific IMRT plans
owing to ease-of-use factors. We have developed a simplified protocol that avoids
complications encountered in commonly used methods. METHODS: We evaluated the
simplified protocol by collecting dose-response data from six production lots of
EBT3 film at doses up to 480 cGy. In this work, we used eight different scanners
of two different models - Epson 10000XL and V700; post-exposure times before
scanning from 30 minutes to 9 days; ambient temperatures for scanning spanning 23
degrees F and two film orientations. Scanning was in 48-bit rgb format at 72 dpi
resolution. Dose evaluation was conducted using a triple-channel dosimetry
method. To validate the simplified protocol, patient specific IMRT QA was
performed using a Varian Trilogy Linac to expose EBT3 films. Scanning and film
analysis was done following the protocol. RESULTS: The results indicated that the
dose-response data could be fit by a set of related rational functions leading to
the description of a universal calibration curve. A simplified protocol was
established where dose-response data for a specific film lot, scanner, and
scanning conditions could be derived from no more than two films exposed to known
doses. In most cases only one calibrated exposure was required. Using the Gamma
test criterion of 2%/2mm to evaluate the measurements, passing rates ranged
between 95% and 99%. CONCLUSIONS: We have demonstrated a simplified protocol to
measure doses delivered by an IMRT treatment plan using only the patient film,
one calibration film, one unexposed film, and applying a single scan to acquire a
digital image for calculation and analysis. The simplification and time-savings
provide a practical solution for using radiochromic film for routine IMRT QA
without sacrificing spatial resolution for convenience. David Lewis, Andre Micke
and Xiang Yu are all employed by Ashland Specialty Ingredients the manufacturer
of GAFCHROMIC EBT3 radiochromic film that is the subject of the work presented in
the Abstract.
PMID- 28517800
TI - SU-E-T-203: Development of a QA Software Tool for Automatic Verification of Plan
Data Transfer and Delivery.
AB - PURPOSE: Consistency verification between the data from treatment planning system
(TPS), record and verification system (R&V), and delivered recorder with visual
inspection is time consuming and subject to human error. The purpose of this work
is to develop a software tool to automatically perform such verifications.
METHODS: Using Microsoft visual C++, a quality assurance (QA) tool was developed
to (1) read plan data including gantry/collimator/couch parameters, multi-leaf
collimator leaf positions, and monitor unit (MU) numbers from a TPS (Xio,
CMS/Elekta, or RealART, Prowess) via RTP link or DICOM transfer, (2) retrieve
imported (prior to delivery) and recorded (after delivery) data from a R&V system
(Mosaiq, Elekta) with open database connectivity, calculate MU independently
based on the DICOM plan data using a modified Clarkson integration algorithm, and
(4) compare all the extracted data to identify possible discrepancy between TPS
and R&V, and R&V and delivery. RESULTS: The tool was tested for 20 patients with
3DCRT and IMRT plans from regular and the online adaptive radiotherapy
treatments. It was capable of automatically detecting any inconsistency between
the beam data from the TPS and the data stored in the R&V system with an
independent MU check and any significant treatment delivery deviation from the
plan within a few seconds. With this tool being used prior to and after the
delivery as an essential QA step, our clinical online adaptive re-planning
process can be speeded up to save a few minutes by eliminating the tedious visual
inspection. CONCLUSIONS: A QA software tool has been developed to automatically
verify the treatment data consistency from delivery back to plan and to identify
discrepancy in MU calculations between the TPS and the secondary MU check. This
tool speeds up clinical QA process and eliminating human errors from visual
inspection, thus improves safety.
PMID- 28517801
TI - SU-E-T-175: A Study on Design and Fabrication of 25 * 25 cm2 Beam Monitor for
Scanning Carbon Beam.
AB - PURPOSE: The KHIMA is developing a superconducting cyclotron of 430 MeV/u for
carbon therapy. In order to verify the irradiated beam dose and position,
detectors have been developed. The detector has a considered in the active area
of 25*25cm2 to cover the entire beam scanning area. To minimize the loss of data
during beam irradiation, a fast data acquisition system was required. METHODS: A
PPIC type was adopted. To measure the beam position and profile, the electrode of
PPIC was designed to have a strip pattern. The PCB technique was applied to large
area with thin FR-4 plate of electrodes. The chamber has a strip interval of
1.7mm. He was used as the filling gas in order to reduce the ion collection time.
Output signal from the detector connected to the two charge integrators was
transferred every 10us. The signal can be stored temporarily in memory of FPGA
through one of 2 integrators. RESULTS: The fabricated large electrode plates did
not show any deformation on their shape. Depending on the beam position, the
amount of dose from the ion chamber will be measured. For fast data acquisition,
the DAQ board was fabricated by using 2 charge integrators and the FPGA. The
obtained data from the ion chamber was displaced on the PC screen every 10us. The
fluence map of a single layer will be shown on the PC screen at the end of beam
irradiation on the layer. The output data from the profile monitor will be
compared with Gafchromic Film results. CONCLUSIONS: PCB method for active area of
thin electrodes was used in the strip pattern. To reduce the loss of data during
irradiation, 2 charge integrators are used alternately. The response of the
readout data was set 1 0us. The beam tests will be performed with the MC-50
Cyclotron.
PMID- 28517802
TI - SU-E-T-147: Film Dosimetry Verification for TSE Using An Epson Scanner.
AB - PURPOSE: To commission and verify an Epson scanner for film dosimetry for total
skin electron beam therapy (TSEB). METHODS: Use data from an IBA PPC40 parallel
plate ion chamber and Sun Nuclear QED skin diode detectors as standard; we have
made comparisons to the film measurement using Kodak XV films. Hurter-Driffield
(HD) curve are established for 6 MeV total skin electron beams at a source-to
surface distance (SSD) of 5 m. Also HD curves are built for 6 MeV at a 100 cm
SSD. Dose profiles for a series of oblique incident large electron fields are
measured using the film for approximately 80 cGy dose delivered at the peak. The
film is then scanned using two scanners, an Epson expression 10000 XL and a Vidar
VXR-16 Dosimetry Pro. The optimal scanning conditions (e.g., dot per pixel size,
internal color correction scheme) are chosen for the Epson scanner. Matlab is
then used to analyze the optical density (OD) of the scanned films. A
transmission densitometer made by Tobias Associates transmission is used to
analyze the films to give a classical standard. RESULTS: The analysis of the
Epson scanner is presented in two forms: one with and one without the HD
correction from the established HD curve. The error analysis gives an uncertainty
of 5% without the HD correction. An improved result of approximately 3% is found
when an HD correction is applied to the analysis. CONCLUSIONS: A simple Epson
scanner satisfies the commissioning standards for TSEB when an HD curve
correction is applied.
PMID- 28517803
TI - SU-E-T-187: Clinical Use of the Software for the Automation of Treatment Field
Parameters Verification Prior to Radiation Delivery.
AB - PURPOSE: Verification of treatment field parameters by therapists take place
prior to every or first fraction. Such verification or field timeout should be
completely independent from record-and-verify system. It is performed manually
via reading treatment parameters from linac screen and comparing them to
treatment plan. We evaluate clinical use of software allowing automation of field
timeout. METHODS: The program for automated timeout performs three tasks.Plan
information is extracted from PDF printouts generated by Eclipse (Varian Medical
Systems, Palo Alto, CA) treatment planning system. User selects patient, plan and
field to be compared with the field moded-up at the linac. Information from the
Varian (Varian Medical Systems) linac's screen is extracted using video signal
splitter and VGA2USB converter (Epiphan Systems, Ottawa, CA). Image farther
undergoes character recognition, which works reliably for 1X, Trilogy and 2100C
linacs used in out tests.The plan and linac screen information are output to the
computer screen and user is alerted if mismatch is observed. The software uses
tolerances established in out clinic. The program also outputs auxiliary
information, e.g. bolus, which is not well alerted by or can be omitted in the
record and verify system. In the workflow tested, PDF printouts are uploaded for
the software during second check and automatic timeout is performed for all
treatments except v-sim and first fraction (of each treatment plan). RESULTS: The
software has friendly user interface and is easily included in clinical work
flow. With the error rate being extremely low, we don't have data yet to claim
that automated timeout provides higher safety than manual; however, it definitely
cuts timeout time to 2-3sec per fields versus 10sec, if done manually.
CONCLUSIONS: Field timeout automation is practicable and fits well into clinical
workflow. It improves patient throughput and is expected to improve patient
safety. CONFLICT OF INTEREST: S. Kriminski and I. Lysiuk: provisional patent
application is submitted to United States Patent and Trademark Office.
PMID- 28517804
TI - SU-E-T-158: Neutron Damage of Power Electronics Used during Image Guidance in
Proton Therapy.
AB - PURPOSE: A series of measurements were performed in a clinical proton therapy
beam to assess the sensitivity of silicon-based electronics in commercial x-ray
generators to single event burnout from the secondary neutron background in
proton therapy treatments. METHODS: Failure rates were nondestructively measured
in various metal oxide semiconductor field-effect transistors (MOSFETs) as a
function of applied voltage using a dedicated test circuit board. Neutrons were
produced by 230 MeV protons stopping in a brass beam target and high beam current
was used to accelerate testing. Neutron fluences were measured by activation
analysis of carbon and aluminum in both the test setup and in situ at the
generator. Failure rates were determined by scaling results based on beam monitor
output to the relevant neutron fluence rate. RESULTS: Current pulses from the
test board clearly indicated the onset of single event burnout without destroying
the MOSFET. The neutron fluence measured on the test board was 4.3 +/- 0.8*106 n
cm-2 MU-1 and this is consistent with previous measurements. The MOSFET failure
rate decreased rapidly with a reduction in the applied voltage and is 20-30 times
lower in higher-rated components at the same voltage. Under nominal operating
conditions the estimated failure rate is tens of failures per year for a
generator 6m from the treatment position. CONCLUSION: The sensitivity of x-ray
generator power electronics to neutron-induced single-event burnout is
significant and can affect the implementation of image-guided techniques for
proton therapy. Strategies and system designs to mitigate this phenomenon are
being investigated to help enable x-ray generators withstand the proton therapy
environment. This research was supported by the NIH/NCI under grant number 6-PO1
CA 21239.
PMID- 28517806
TI - SU-E-T-169: Initial Investigation into the Use of Optically Stimulated
Luminescent Dosimeters (OSLDs) for In-Vivo Dosimetry of TBI Patients.
AB - PURPOSE: To report on an initial investigation into the use of optically
stimulated luminescent dosimeters (OSLDs) for in-vivo dosimetry for total body
irradiation (TBI) treatments. Specifically, we report on the determination of
angular dependence, sensitivity correction factors and the dose calibration
factors. METHODS: The OSLD investigated in our work was InLight/OSL nanoDot
dosimeters (Landauer Inc.). Nanodots are 5 mm diameter, 0.2 mm thick disk-shaped
Carbon-doped Al2O3, and were read using a Landauer InLight microstar reader and
associated software.OSLDs were irradiated under two setup conditions: a) typical
clinical reference conditions (95cm SSD, 5cm depth in solid water, 10*10 cm field
size), and b) TBI conditions (520cm SSD, 5cm depth in solid water, 40*40 cm field
size,). The angular dependence was checked for angles ranging +/-60 degree from
normal incidence. In order to directly compare the sensitivity correction
factors, a common dose was delivered to the OSLDs for the two setups. Pre- and
post-irradiation readings were acquired. OSLDs were optically annealed under
various techniques (1) by keeping over a film view box, (2) Using multiple scan
on a flat bed optical scanner and (3) Using natural room light. RESULTS: Under
reference conditions, the calculated sensitivity correction factors of the OSLDs
had a SD of 2.2% and a range of 5%. Under TBI conditions, the SD increased to
3.4% and the range to 6.0%. The variation in sensitivity correction factors
between individual OSLDs across the two measurement conditions was up to 10.3%.
Angular dependence of less than 1% is observed. The best bleaching method we
found is to keep OSLDs for more than 3 hours on a film viewer which will reduce
normalized response to less than 1%. CONCLUSIONS: In order to obtain the most
accurate results when using OSLDs for in-vivo dosimetry for TBI treatments,
sensitivity correction factors and dose calibration factors should all be
determined under clinical TBI conditions.
PMID- 28517807
TI - SU-E-T-179: MVCB Pelvic Surface Dosimetry.
AB - PURPOSE: To compare commonly clinically available methods of estimating skin dose
for a Megavoltage Conebeam CT of the pelvis. METHODS: The clinical 6 MV conebeam
uses 15 MU on a Siemens Oncor linac. Film tests using XV-2 film were done on a
solid water phantom, as were tests using a parallel plate ion chamber at 2 mm
depth. A Rando pelvic phantom was set up for a MVCB CT, and a cylindrically
symmetric Isorad 6-12 MV PDM diode was placed at various angles around the
phantom and irradiated using a 150 MU 6 MV arc beam with the same geometry as the
clinical conebeam, giving higher and more accurate readings than would be
obtained with the 15 MU conebeam. A comparison was made with the Pinnacle 8.0m
treatment planning system. A strip of Optically Stimulated Luminescence
dosimeters provides an accurate check of the surface dose distribution. RESULTS:
All methods revealed an expected lateral asymmetry in the dose due to the
starting and stopping angles of 270 (-90) and 110 for the conebeam. On the sides
of the phantom, the diode dose was comparable to the Pinnacle-calculated dose at
a depth of 3-5 mm. Near the anterior portion the diode dose was about 5% higher
than the maximum Pinnacle-calculated dose at that angle. This difference is
partly due to the increased diode response at shorter SSDs and higher dose rates,
and to the geometry with the arc beam radiation being mainly anterior to
posterior. The skin dose, corresponding to a depth of about 2 mm, is expected to
be somewhat lower. CONCLUSIONS: To estimate pelvic skin dose in the MV CB
geometry, corrections for measurement depth and geometry can be used to improve
the dosimetry for these common clinically available dosimeters.
PMID- 28517805
TI - SU-E-T-197: A Comprehensive Variance Reporting System and an Analysis of
Variances Reported at Our Institution.
AB - PURPOSE: It is essential for radiation oncology departments to have comprehensive
patient safety and quality programs. Two years ago we undertook a systematic
review of our safety/QA program. Existing policies were updated and new policies
created where necessary. One crucial component of any safety/QA program is
continually updating it based on current information, the 'check' and 'act'
portions of the Deming Cycle. We accomplished this with a transparent variance
reporting system and a safety/QA committee reviewing and acting on reported
variances. METHODS: With 5 radiation oncology centers in our institution, we
needed to devise a system that would allow anyone to report a variance and
provide our QA committee the ability to review variances system-wide. We
developed the system using web-based tools. The system allows individuals to
report variances, anonymously or named, specify the nature of the variance and
indicate the tools used to identify the variance. RESULTS: In 2011, 285 variances
were reported, 102 were reported by physicists, 86 anonymously, 71 by therapists
and 26 by dosimetrists. We realized the need to develop clear classifications for
variances. We added a high priority category, defined as variances which resulted
in or had the potential to result in harm to a patient or when a policy is
purposely overridden. Of the 285 variances reported, 5 were high priority. We
created a process variance category, defined as variances where a specific
clinical process is not followed. Of the 285 reported variances 155 were process
variances. CONCLUSIONS: Reporting of variances through a centralized database is
central toward developing a robust patient safety/quality assurance program.
Anonymous reporting fosters a non-punitive environment, and promotes the 'safety
culture'. The goal of such a system is to review trends in clinical processes and
ultimately to improve safety/quality by reducing variances associated with these
processes.
PMID- 28517808
TI - SU-E-T-151: Effect of Surface Dose and Depth of Maximum Dose with Physical Wedge
Filters for 6MV Flattened and 7MV Unflattened Photon Beams.
AB - PURPOSE: To evaluate impact on surface dose, Depth of dose maximum (dmax) and
depth dose distribution due to physical wedge filters for different wedge angle
were studied for 6MV flattened (6MV FB) and 7MV unflattened (7MV UFB) photon
beams. METHODS: The flattening filter and primary collimator are the major
sources of producing the scattered radiation and these parameters affect the
surface dose, dmax and dose distribution. In this study, open fields surface
dose, dmax and depth dose distribution values were compared with physical wedge
filter for 6MV FB and 7MV UFB .The measurement carried out in Siemens - ARTISTE
linear accelerator with diode detector along the central axis of the beam at 100
cm source to surface distance using IBA blue water phantom for 6MV FB and 7MV UFB
x-ray beams. RESULTS: The surface dose increased as the field size increased for
open and physical wedge fields for 6MV FB and 7MV UFB beams. For open fields,
Surface doses relative to the dose at dmax ranged from 0.443 to 0.569 and 0.463
to 0.668 for field sizes of 5 * 5 to 20*20 cm2 for the 7MV UFB and 6MV FB beam
respectively. The measured surface dose for 150, 300,450 and 600 wedge field
values are 0.396 to 0.504, 0.366 to 0.484, 0.342 to 0.464 and 0.347 to 0.47
respectively for 7MV UFB and 0.424 to 0.566, 0.398 to 0.555, 0.3860 to 0.5430 and
0.389 to 0.55 respectively for 6MV FB. CONCLUSIONS: We found that dmax of wedged
beams were higher than those open beams for field size up to 10 * 10 cm2 ,
Surface doses of wedged beams were lower than those of open beams for 7MV UFB and
6MV FB. Surface dose of the 7MV UFB were lower than the 6MV FB for open and
wedged beams.
PMID- 28517810
TI - SU-E-T-181: Development of a Single-Marker-Based Optical Tracking System to
Enhance Patient Safety in Radiotherapy.
AB - PURPOSE: To develop an accurate and efficient single-marker-based optical
tracking system to enhance patient safety and quality of care in radiotherapy.
METHODS: The optical tracking system consists of a Polaris camera as well as in
house software. The camera is mounted inside the treatment room and detects the
location of a single infra-red (IR) reflective marker affixed on patient skin in
real-time. The tracking system safeguards patient from treating wrong sites by
comparing real-time marker position to the position predicted by virtual
simulation, which is independent of couch or any indexing system. The deviation
of marker position is shown in color (red or green) to indicate accuracy of
patient positioning. The system works in concert with record-and-verify (R&V)
system to further enhance patient safety and smooth clinic work flow. Marker
information matching the patient under treatment is automatically loaded by the
tracking system when a setup or treatment field is loaded in R&V. In non-coplanar
treatment, the system automatically adjusts expected marker coordinators by
accounting for each beam's couch angle extracted from R&V. RESULTS: Accuracy of
the developed tracking system on a pelvis phantom has been verified against a
CBCT system to be within 1.0 mm for coplanar treatment. In non-coplanar
treatment, uncertainty of the system increases as the distance of the marker
relative to treatment isocenter. The system precisely and automatically loads in
patient and marker information for each beam, in concert with our R&V system.
CONCLUSIONS: We have developed an accurate and efficient single IR marker-based
optical tracking system for patient treatment position verification. It
significantly enhances patient safety with streamlined clinic work flow. The
system can be readily upgraded for high-precision radiotherapy with the use of
multiple markers (>4).
PMID- 28517811
TI - SU-E-T-153: Detector-Grade CVD Diamond for Radiotherapy Dosimetry.
AB - PURPOSE: To evaluate the use of commercially available detector-grade synthetic
diamond films made via chemical vapor deposition (CVD) as x- ray detectors for
radiotherapy dosimetry. METHODS: A detector was fabricated using high-quality
single crystal CVD diamond films (0.5 * 3 * 3 mm3) with 0.4 mm3 sensitive
volumes, which were encapsulated with PMMA. The detector was placed in a (30 * 30
* 30 cm3) PTW water phantom. Six- and ten-MV photons from an Elekta Synergy linac
were measured using an SSD of 90 cm and typically a 10-cm phantom depth with a 10
* 10 cm2 field size in the central axis of the beam. Data acquisition was
performed using a PTW UNIDOS E electrometer with a 100-V bias. The detector was
evaluated by measuring leakage current, priming dose, response dynamics, dose
linearity, dependence on dose rate, percent depth dose (6 and 10 MV photons) and
output factors. Some measurements were compared with a Si diode detector, 0.04
and/or 0.13-cc ion chamber(s). RESULTS: Leakage currents were negligible (~1 pA)
given the overall average sensitivity of the material (680 nC/Gy at 100 V).
Detector current rise and fall times were < 2 s. Dose measurements up to 5 Gy
were linear. A slight dependence on nominal dose rates up to 500 MU/min was seen
with Fowler fitting parameter delta = 0.981. Percent depth dose profiles compared
well to a 0.13-cc ion chamber up to 25 cm depths for 10-MV photons. Output
factors measured well for field widths 5-15 cm; below 5 cm, differences are seen
between all four different detectors as expected. CONCLUSIONS: The type of
diamond tested has potential to be used for small field dosimetry due to its
small sensitive volume and high sensitivity. Further experiments are ongoing and
detector packaging is yet to be optimized.
PMID- 28517809
TI - SU-E-T-190: Design, Development, and Evaluation of a Modified, Anthropomorphic,
Head, Quality Assurance Phantom for Use in Stereotactic Radiosurgery.
AB - PURPOSE: To develop and evaluate a modified anthropomorphic head phantom for
evaluation of stereotactic radiosurgery (SRS) dose planning and delivery.
METHODS: A phantom was constructed from a water equivalent, plastic, head-shaped
shell. The original phantom design, with only a spherical target, was modified to
include a nonspherical target (pituitary) and an adjacent organ at risk (OAR)
(optic chiasm), within 2 mm, simulating the anatomy encountered when treating
acromegaly. The target and OAR spatial proximity provided a more realistic
treatment planning and dose delivery exercise. A separate dosimetry insert
contained two TLD for absolute dosimetry and radiochromic film, in the sagittal
and coronal planes, for relative dosimetry. The prescription was 25Gy to 90% of
the GTV with >= 10% of the OAR volume receiving >= 8Gy. The modified phantom was
used to test the rigor of the treatment planning process, dosimeter
reproducibility, and measured dose delivery agreement with calculated doses using
a Gamma Knife, CyberKnife, and linear accelerator based radiosurgery systems.
RESULTS: TLD results from multiple irradiations using either a CyberKnife or
Gamma Knife agreed with the calculated target dose to within 4.7% with a maximum
coefficient of variation of+/-2.0%. Gamma analysis in the coronal and sagittal
film planes showed an average passing rate of 99.3% and 99.5% using +/-5%/3mm
criteria, respectively. A treatment plan for linac delivery was developed meeting
the prescription guidelines. Dosimeter reproducibility and dose delivery
agreement for the linac is expected to have results similar to the results
observed with the CyberKnife and Gamma Knife. CONCLUSIONS: A modified
anatomically realistic SRS phantom was developed that provided a realistic
clinical planning and delivery challenge that can be used to credential
institutions wanting to participate in NCI funded clinical trials. Work supported
by PHS CA010953, CA081647, CA21661 awarded by NCI. DHHS.
PMID- 28517812
TI - SU-E-T-192: Computer Vision for Final Online Treatment Parameter Verification.
AB - PURPOSE: In a typical model of Radiation Oncology data flow, treatment plan is
designed on treatment planning station (TPS) under the supervision of physician
and physicist, and machine specific parameters are pushed to Record and Verify
system (RV) for treatment data storage, where it stays available for daily
uploads to treatment station. While various QA programs could be established to
verify uncorrupted planning data storage and transfer, the ultimate goal is a
daily confirmation of patient treatment parameters versus original treatment
plan. METHODS: A new computer vision approach, RTcheck, is used to digitize
loaded machine parameters directly from the screen of Varian Clinical Console
every time before the beam is turned on by a therapist. The verification engine
runs a check against the parameters automatically extracted from the printed
postscript planning report (Pinnacle, Philips) prepared during planning stage and
approved by physician. All important beam data, MUs, jaws position, beam energy,
couch angle, and wedge specifiers are displayed side by side on the screen of
RTcheck station. All field verifications are recorded to a log file, periodically
reviewed by a physicist. RESULTS: In our clinical tests, the electronic
verification of machine treatment parameters shortened patient 'on the table'
time, as the manual therapist's 'time out' check before every beam on may take up
to several minutes for patient treatments with multiple beams (more than 10). Our
analysis of verification logs revealed several instances of a small X1 jaw
position discrepancy of 0.1cm for jaw position range of 0 to -2cm. After jaw
recalibration, the problem was eliminated. CONCLUSIONS: RTcheck is the end-to-end
quality assurance approach to verify data flow from TPS to treatment machine for
every patient treatment. Computer vision approach may help reduce human error
factor, and shorten patient treatment time. CONFLICT OF INTEREST: S. Kriminski
and I. Lysiuk: provisional patent application is submitted to United States
Patent and Trademark Office.
PMID- 28517813
TI - SU-E-T-164: Clinical Implementation of ASi EPID Panels for QA of IMRT/VMAT Plans.
AB - PURPOSE: To investigate various issues for clinical implementation of aSi EPID
panels for IMRT/VMAT QA. METHODS: Six linacs are used in our clinic for EPID
based plan QA; two Varian Truebeams, two Varian 2100 series, two Elekta Infiniti
series. Multiple corrections must be accounted for in the calibration of each
panel for dosimetric use. Varian aSi panels are calibrated with standard dark
field, flood field, and 40*40 diagonal profile for beam profile correction.
Additional corrections to account for off-axis and support arm backscatter are
needed for larger field sizes. Since Elekta iViewGT system does not export gantry
angle with images, a third-party inclinometer must be physically mounted to back
of linac gantry and synchronized with data acquisition via iViewGT PC clock. A
T/2 offset correctly correlates image and gantry angle for arc plans due to iView
image time stamp at the end of data acquisition for each image. For both Varian
and Elekta panels, a 5 MU 10*10 calibration field is used to account for the
nonlinear MU to dose response at higher energies. Acquired EPID images are
deconvolved via a high pass filter in Fourier space and resultant fluence maps
are used to reconstruct a 3D dose 'delivered' to patient using DosimetryCheck.
Results are compared to patient 3D dose computed by TPS using a 3D-gamma
analysis. RESULTS: 120 IMRT and 100 VMAT cases are reported. Two 3D gamma
quantities (Gamma(V10) and Gamma(PTV)) are proposed for evaluating QA results.
The Gamma(PTV) is sensitive to MLC offsets while Gamma(V10) is sensitive to
gantry rotations. When a 3mm/3% criteria and 90% or higher 3D gamma pass rate is
used, all IMRT and 90% of VMAT QA pass QA. CONCLUSIONS: After appropriate
calibration of aSi panels and setup of image acquisition systems, EPID based 3D
dose reconstruction method is found clinically feasible.
PMID- 28517814
TI - SU-E-T-202: Comprehensive Quality Assurance Procedures for Uniform Scanning
Proton Therapy Machines.
AB - PURPOSE: Quality assurance (QA) is essential in safe and accurate delivery of
radiation therapy. However, QA in proton therapy is challenging due to
complicated and often facility-specific beam delivery systems and limited beam
time for QA. The purpose of this study is to develop an efficient and
comprehensive QA procedure for a multi-room proton therapy center using uniform
scanning beams. METHODS: Our proton therapy center is comprised of a 230 MeV
cyclotron, one fixed beam room, two inclined beam rooms, and one gantry room.
Uniform scanning is employed exclusively in all treatment rooms. A rfDaily QA3
(Sun Nuclear Inc., Melbourne, Florida) together with home-made devices is used
for daily QA. Parallel plane chambers, a multi-layer ionization chamber array
(Zebra, IBA dosimetry, Schwarzenbruck, German), and an IC profiler (Sun Nuclear
Inc., Melbourne, Florida) are used to QA the characteristics of the uniform
scanning beams, including output, range, modulation width, flatness, symmetry,
and penumbra, for both monthly and annual QA. QA procedures and acceptance
criteria were developed, taking into account the likelihood and potential risk of
failure, as well as the available equipment, personnel and other resources.
RESULTS: QA procedures and tolerances were developed for daily, monthly and
annual QA at our proton therapy center. Daily QA is performed by radiation
therapists, and can be completed within 30 minutes for all rooms. Monthly QA and
annual QA are performed by physicists, taking about 4 hours and a weekend
respectively. Trend analysis was performed for various machine characteristics,
such as machine output, range, flatness, and symmetry. CONCLUSION: QA standards
are desired in Radiation Oncology, but not many standards are developed and
available for proton therapy. In the mean time, facility-specific QA procedures
should be developed based on the equipment failure modes and available resources.
PMID- 28517815
TI - SU-E-T-146: Reference Dosimetry for Protons and Light-Ion Beams Based on Graphite
Calorimetry.
AB - PURPOSE: The IAEA TRS-398 code of practice can be applied for the measurement of
absorbed dose to water under reference conditions with an ionization chamber. For
protons, the combined relative standard uncertainty on those measurements is less
than 2% while for light-ion beams, it is considerably larger, i.e. 3.2%, mainly
due to the higher uncertainty contributions for the water to air stopping power
ration and the W air-value on the beam quality correction factors kQ,Q0 . To
decrease this uncertainty, a quantification of kQ,Q0 is proposed using a primary
standard level graphite calorimeter. This work includes numerical and
experimental determinations of dose conversion factors to derive dose to water
from graphite calorimetry. It also reports on the first experimental data
obtained with the graphite calorimeter in proton, alpha and carbon ion beams.
METHODS: Firstly, the dose conversion has been calculated with by Geant4 Monte
Carlo simulations through the determination of the water to graphite stopping
power ratio and the fluence correction factor. The latter factor was also derived
by comparison of measured ionization curves in graphite and water. Secondly,
kQ,Q0 was obtained by comparison of the dose response of ionization chambers with
that of the calorimeter. RESULTS: Stopping power ratios are found to vary by no
more than 0.35% up to the Bragg peak, while fluence correction factors are shown
to increase slightly above unity close to the Bragg peak. The comparison of the
calorimeter with ionization chambers is currently under analysis. For the
modulated proton beam, preliminary results on W air confirm the value recommended
in TRS-398. Data in both the non-modulated proton and light-ion beams indicate
higher values but further investigation of heat loss corrections is needed.
CONCLUSIONS: The application of graphite calorimetry to proton, alpha and carbon
ion beams has been demonstrated successfully. Other experimental campaigns will
be held in 2012. This work is supported by the BioWin program of the Wallon
Government.
PMID- 28517817
TI - SU-E-T-157: Reproducibility of CVD Diamond Detectors for Radiotherapy Dosimetry.
AB - PURPOSE: Three diamond x-ray detectors fabricated in-house using films from the
same batch of commercially-available chemical vapor deposition (CVD) diamond were
investigated for performance inter-comparability under clinically relevant
conditions. METHODS: Detectors were based on single-crystal CVD diamond films
(0.5 * 3 * 3 mm3) with 0.4 mm^3 sensitive volumes, which were encapsulated with
PMMA. Detectors were placed in a (30 * 30 * 30 cm3) PTW water phantom. Six-MV
photons from an Elekta Synergy linac were measured using an SSD of 90 cm and 10
cm phantom depth with a 10 * 10 cm2 field size in the central axis of the beam.
Data acquisition was performed using a PTW UNIDOS E electrometer. Leakage
current, priming dose, response dynamics, dose linearity, dependence on dose rate
and angular dependence were used to evaluate differences between diamond
detectors. RESULTS: Differences were seen in leakage currents before (< 1.5 pA)
and after (< 12 pA) irradiation. A priming dose of ~7 Gy and rise and fall times
of 2 s were found for all three detectors. Sensitivities differed by up to 10%.
Dependence on dose rate was similar (Fowler fitting parameter, delta = 0.92
0.94). Angular dependence was minimal (97-102% average). Differences in detector
performance appeared to be primarily due to film thickness, which can
significantly change sensitivities and applied fields for detectors with small
sensitive volumes. CONCLUSIONS: Although films were sourced from the same
manufactured batch, small deviations were seen between detectors such that
correction factors may be required much like natural diamonds used in existing
commercial detectors. Differences in sensitivity and dependence on dose rate most
likely originate from variation in film thickness due to manufactured tolerances.
Preselecting films by thickness is important to help eliminate variability in
detector response where small sensitive volumes are used.
PMID- 28517816
TI - SU-E-T-186: An Automated Quality Assurance Tool for HDR Treatment Planning.
AB - PURPOSE: Treatment planning for high dose rate (HDR) brachytherapy requires many
user inputs, all of which are potential sources of error. The goal of quality
assurance (QA) is to ensure that errors are not made. In this study, we developed
a software program to analyze the treatment printout from the HDR treatment
planning computer and flag any suspected errors. METHODS: The treatment printout
from the HDR planning computer is imported by the software. The software then
performs the following checks: (1) verifies that the correct source was chosen
(we have multiple in our database), (2) performs an independent decay of the Ir
192 source, (3) verifies source step size, (4) verifies the offsets and indexer
lengths in the catheter definitions based upon expected values for the applicator
used, (4) performs an independent 2nd check of dose to a cloud of dose points
surrounding the treatment region, (5) verifies that the dose per fraction and the
number of fractions were entered correctly in the planning computer, and (6)
verifies that the dose volume histogram (DVH) metrics were within acceptable
tolerances. The software then prints this information to a PDF file, which is
appended to the original treatment printout and placed in the patient's medical
record. RESULTS: This QA tool has now been implemented for six months in our
clinic, and is a critical QA tool in our HDR program. Although each plan is
checked by an independent 2nd physicist, this tool provides an additional
independent check on the treatment plan. CONCLUSIONS: A simple series of
automatic 2nd checks helps reduce the risk of errors occurring in the treatment
planning portion of HDR brachytherapy and can easily be implemented.
PMID- 28517818
TI - SU-E-T-196: Commissioning for Volumetric Modulated Radiation Therapy on Varian
Clinac 21EX.
AB - PURPOSE: Recently the volumetric arc therapy (VMAT) technology such as RapidArc
is widely distributed in Japan. These technologies are normally provided by the
high spec linear accelerator such as Trilogy, Novalis Tx, Synergy, et al. The
specific DICOM-file is generally used for commissioning of these technologies. On
the other hand, we had to apply RapidArc into historic linear accelerator. This
title expresses an experience how we performed the commissioning of RapidArc with
the old linear accelerator. METHODS: Two Varian's linear accelerators "Clinac
21EX" equipped with Millenium multi-leaf collimator and a Varian's treatment
planning system "Eclipse ver.8.9" were used for this study. The commissioning for
RapidArc was performed in energy 4,6,10,15 MV (Max-DR: 250, 600, 400, 600
MU/min). Commissioning procedure composed two categories: the general machine QA
for DMLC-IMRT procedure and the specific RapidArc QA procedure. In RapidArc QA
procedure, we modified DICOM-file to apply into the potential spec of Clinac 21EX
optimally. The specific MLC-motion sequence and the gantry rotation speed were
created by the dedicated programs (Shaper and DicomEdit, Varian) for RapidArc QA
procedure. Each tolerance value was defied by the data from daily/monthly QA and
the paper by Ling et al. RESULTS: As the results of the general machine QA
procedure, the variance of radiation output during static/dynamic gantry rotation
was less than 1%. The deference of fence tests during static/dynamic gantry
rotation and RapidArc were less than 1 mm in each. However, the results of the
RapidArc QA were worse than the latest machine (especially variable gantry speed)
and it was careful to define tolerance level. CONCLUSION: The procedure of
commissioning for RapidArc on historic linear accelerator was proposed. Several
minor revisions for DICOM-file should be required for suitable commissioning and
it may ensure the tolerance limit for gantry/MLC-leaf motion speeds.
PMID- 28517819
TI - SU-E-T-168: Development of a Liquid Scintillation Detector for External Beam
Dosimetry.
AB - PURPOSE: The goal of this research was to design a liquid scintillation dosimeter
that could be used forrelative dosimetry of linear accelerator fields. The
project emphasized minimization of cost and ease of use. METHODS: The
scintillator that was used in this research was BETAMAX- ES scintillation
cocktail from MPBiomedical. This particular scintillator was selected due to its
relatively high scintillation yield and lowcost. The entirety of the scintillator
used the measurements was supplied free of cost. The housing for the liquid was
constructed from PVC and is cylindrical with one tapered end. One fiber of the
dual optical fibers transmits the generated photons to the CCD while the other
fiber is used for Cerenkovsubtraction.The detector used comes from a Philips
SPC880NC webcam. The plastic casing of the webcamwas removed so that only the
printed circuit board, USB cable and lens eyepiece holder remained. Thesensor
employed is the Sony ICX098QB CCD, which is 3.2mm by 2.4mm and each pixel is
5.6mm by 5.6mm. A small cylindrical insert was manufactured that was inserted
into the lens eyepiece holder to get adequate mechanical coupling of the fibers
to the CCD face. Images were acquired with a freeware image acquisition tool,
SharpCap, and analyzed with theMatlab commercial math package from Mathworks.
RESULTS: Measurements have been performed that show that the detector is able to
accurately measuretissue maximum ratio and the relative dose factor. The detector
was able to accurately measurephysical wedge factors and made good predictions of
the modulation factor for a patient's 7-field IMRT plan. CONCLUSIONS: This work
has shown that relative dosimetry can be performed using an inexpensive
liquidscintillation detector. This could be expanded to include an array of
liquid scintillator cells formeasurement of beam profiles and other more complex
problems.
PMID- 28517820
TI - SU-E-T-178: Optically Stimulated Luminescence (OSL) Dosimetry: A Study of A
Al2O3:C Assessed by PENELOPE Monte Carlo Simulation.
AB - PURPOSE: To use the Monte Carlo code PENELOPE to study attenuation and tissue
equivalence properties of a-Al2O3:C for OSL dosimetry. METHODS: Mass attenuation
coefficients of alpha-Al2O3 and alpha-Al2O3:C with carbon percent weight
concentrations from 1% to 150% were simulated with PENELOPE Monte Carlo code and
compared to mass attenuation coefficients from soft tissue for photon beams
ranging from 50kV to 10MV. Also, the attenuation of primary photon beams of 6MV
and 10MV and the generation of secondary electrons by alpha-Al2O3 :C dosimeters
positioned on the entrance surface of a water phantom were studied. RESULTS: A
difference of up to 90% was found in the mass attenuation coefficient between the
pure ?agr;-A12O3 and the material with 150% weight concentration of dopant at 1.5
keV, corresponding to the K-edge photoelectric absorption of aluminum. However
for energies above 80 keV the concentration of carbon does not affect the mass
attenuation coefficient and the material presents tissue equivalence for the
beams studied. The ratio between the mass attenuation coefficients for ?agr
A12O3:C and for soft tissue are less than unit due to the higher density of the
?agr-A12O3 (2.12 g/cms ) and its tissue equivalence diminishes to lower
concentrations of carbon and for lower energies due to the relation of the
radiation interaction effects with atomic number. The larger attenuation of the
primary photon beams by the dosimeter was 16% at 250 keV and the maximum increase
in secondary electrons fluence to the entrance surface of the phantom was found
as 91% at 2MeV. CONCLUSIONS: The use of the OSL dosimeters in radiation therapy
can be optimized by use of PENELOPE Monte Carlo simulation to provide a study of
the attenuation and response characteristics of the material.
PMID- 28517821
TI - SU-E-T-150: The Basic Dosimetric Properties of NIPAM Polymer Gel Dosimeter.
AB - PURPOSE: To asses a series of basic dosimetric properties such as
reproducibility, linearity, tissue equivalency, dose rate and energy independency
for NIPAM polymer gel dosimeter. METHODS: The NIPAM gel was manufactured
according to the method, described by senden et al (2006). The gels were
irradiated approximately 2 h after manufacturing and MR images of the gel were
made 24 h after irradiation. Transverse relaxation rates (R2=T2?1 ) were obtained
from the signal decay data using the proper data analyzer. In order to
investigate the absorbed dose response reproducibility, the experiment was
repeated three times using the same batch of monomer, irradiation method,
scanning parameters and conditions, also with analyzing two set of the gel with
different batches of chemical the effect of different batches were investigated .
For assessing if the NIPAM gel dosimeter response is dependent on different
photon energies, two sets of NIPAM gel were irradiated using a 9 MV linear
accelerator and a 60co. The effect of different dose rate on gel response was
studied in SSD of 80, 90, 100, 110 and 120 and radiation beam were calibrated to
give 5Gy in each SSD. To investigate the linearity of the gel, the vials were
irradiated from 1 to 35 Gy. In order to verify tissue equivalency, effective
atomic number and relative electron density of NIPAM dosimeter were calculated
using CT number, and compared with tissue. RESULTS: This polymer gel found to be
tissue equivalent. The results showed that the dose response of NIPAM polymer gel
is highly reproducible in same and different batches of chemical and its response
was linear up to 26 Gy. Energy and dose rate had no effect on NIPAM gel response.
CONCLUSIONS: NIPAM gel dosimeter appears to be a promising dosimeter in all
aspects of dosimetric properties which were assessed in this study.
PMID- 28517822
TI - SU-E-T-189: Arc Splitting for VMAT Patient QA.
AB - PURPOSE: To determine the need for arc splitting for VMAT prostate patient
quality assurance. METHODS: Prior to Eclipse version 10.0, a verification plan
for VMAT treatment could only be created which mirrored the clinical plan; if the
plan called for a full arc, then the verification plan also contained a full arc.
In this case, for a center that uses the Sun Nuclear MapCheck device with its
Isocentric Mounting Fixture, the full fluence of an arc is delivered en face to
the device. The question arose as to whether partial arcs, if they could be
created, would fail a center's criteria, while the full arc passed them, in
effect, whether there are cancellations occurring and not being observed. With
Eclipse version 10.0, it is now possible to split a clinical arc into many
subdivisions for verification, the software recommends no more than 40 partial
arcs, for computing speed limitations. Twelve VMAT plans for prostate patients
were investigated, in order to search for the aforementioned cancellations. Two
full arcs were used clinically in all cases. Verification plans were created
consisting of (1) the two full arcs; (2) 8 partial arcs of 90 degrees each; and
(3) 16 partial arcs of 45 degrees each. These were all analyzed against our
criteria of 3%/3mm with a threshold of 10%, and 95% of points passing. RESULTS:
Of 288 partial arcs and 49,670 points analyzed, there were a total of 100 points
(0.2%) that failed the 3%/3mm criteria. No arcs, however, failed the 95% passing
criteria. Moreover, there was no evidence of cancellation; if a point failed low,
there was no corresponding high failure in another partial arc. CONCLUSIONS: In
this study, splitting a full arc into partial arcs revealed no unseen failures.
PMID- 28517823
TI - SU-E-T-161: SOBP Beam Analysis Using Light Output of Scintillation Plate Acquired
by CCD Camera.
AB - PURPOSE: To analyze Bragg-peak beams in SOBP (spread-out Bragg-peak) beam using
CCD (charge-coupled device) camera - scintillation screen system. We separated
each Bragg-peak beam using light output of high sensitivity scintillation
material acquired by CCD camera and compared with Bragg-peak beams calculated by
Monte Carlo simulation. METHODS: In this study, CCD camera - scintillation screen
system was constructed with a high sensitivity scintillation plate (Gd2O2S:Tb)
and a right-angled prismatic PMMA phantom, and a Marlin F-201B, EEE-1394 CCD
camera. SOBP beam irradiated by the double scattering mode of a PROTEUS 235
proton therapy machine in NCC is 8 cm width, 13 g/cm2 range. The gain, dose rate
and current of this beam is 50, 2 Gy/min and 70 nA, respectively. Also, we
simulated the light output of scintillation plate for SOBP beam using Geant4
toolkit. RESULTS: We evaluated the light output of high sensitivity scintillation
plate according to intergration time (0.1 - 1.0 sec). The images of CCD camera
during the shortest intergration time (0.1 sec) were acquired automatically and
randomly, respectively. Bragg-peak beams in SOBP beam were analyzed by the
acquired images. Then, the SOBP beam used in this study was calculated by Geant4
toolkit and Bragg-peak beams in SOBP beam were obtained by ROOT program. The SOBP
beam consists of 13 Bragg-peak beams. The results of experiment were compared
with that of simulation. CONCLUSIONS: We analyzed Bragg-peak beams in SOBP beam
using light output of scintillation plate acquired by CCD camera and compared
with that of Geant4 simulation. We are going to study SOBP beam analysis using
more effective the image acquisition technique.
PMID- 28517825
TI - SU-E-T-152: Development of a Phantom for Commissioning and Patient Specific QA
for Volumetric Modulated Arc Therapy (VMAT).
AB - PURPOSE: To design a cost effective phantom for commissioning tests and patient
specific quality assurance in VMAT techniqueMethods: The phantom is made of PMMA
with the physical density of 1.18 gm/cc. It consists of 20 numbers of 20cm
diameter discs connected together in a horizontal stack, making a cylinder of
length 20cm. The centers of the discs are drilled with 2.1cm hole which
accommodates chamber sleeve of near 2.1cm diameter, which is made of Delrin with
the physical density of 1.414gm/cc. The cylindrical geometry of the phantom is
ideal for rotational therapy QA like VMAT or Rapid arc. The entire phantom is
self supporting and hence no supporting bar or holders are in the path of beam
geometry. The chamber sleeve itself acts as the supporting rod for these discs
and it can be inserted in to the disc assembly from distance of-9cm to +10cm from
the origin and hence any axial point from -9cm to +10cm with respect to isocenter
can be used for point dose measurement. The other side of the chamber sleeve is
filled by spacer rod for sustaining the discs in place. The films can be
inserted, transversely in any XZ plane from -9cm to +10cm from the origin between
the discs next to the chamber center. RESULTS: Simultaneous irradiation for the
chamber and the film is done for VMAT plans without collapsing the gantry angles
to nominal angle of zero. Evaluated the results using RIT film analysis software
for gamma index of 3%, 3mm. Good agreement is found with more than 95% of pixels
passing 3% 3mm criteria. The point dose verification showed less than 3%
variation with TPS planned dose. CONCLUSIONS: Most of the commercial QA systems
needs gantry to be collapsed to zero degree to perform QA for modern RT
techniques. Especially for techniques like VMAT, collapsing gantry to zero will
fail to validate the influence of gantry speed on dose delivery.
PMID- 28517824
TI - SU-E-T-199: The Radiological Physics Center's Credentialing Dosimetry Reviews:
Their Effect on Clinical Trial Deviation Rates.
AB - PURPOSE: To describe the Radiological Physics Center's (RPC) methods to evaluate
an institution's ability to meet protocol guidelines in order to decrease NCI
clinical trial deviation rate. METHODS: The RPC's dosimetry group utilizes 3
methods of assessing an institutions ability to meet the protocol treatment
specifications. These methods involve a clinical and dosimetric review of a
treatment plan submitted by the institution prior to the first patient being
treated on a protocol. The three evaluation methods include use of site/treatment
modality specific benchmark cases, evaluation of a previous patient treated in a
similar fashion and a rapid review of the first patient placed on a trial prior
to start of treatment. The dosimetric review consists of an independent dose
recalculation using RPC measured data or RPC standard dosimetry data. The
clinical review assesses the patient's DVHs and contouring of the tumor volume
and critical structures, typically in conjunction with a radiation oncologist.
RESULTS: Over the past 5 years the RPC has performed these QA reviews for several
of the clinical trial groups for several different disease sites and treatment
modalities. We have reviewed 1366 treatment plans as a part of credentialing (97
gynecological, 223 prostate, 1046 breast) where 222 failed the first submission
requiring the RPC to interact with the submitting institution to resolve the
discrepancy. The review of the benchmarks has resulted in 18% of the institutions
requiring intervention by the RPC. Performing these reviews has identified
potential clinical and dosimetric problem areas that could possibly have resulted
in 17% of the charts reviewed to receive a minor or major deviation. CONCLUSIONS:
The RPC's clinical and dosimetry review of submitted treatment plans before or
early in the treatment process has helped to reduce the deviation rates on
protocols. Work supported by PHS grant CA 10953 awarded by NCI, DHHS.
PMID- 28517826
TI - SU-E-T-191: PITSTOP: Process Improvement Techniques, Software Tools, and
Operating Principles for a Quality Initiative Discovery Framework.
AB - PURPOSE: To develop a quality initiative discovery framework using process
improvement techniques, software tools and operating principles. METHODS: Process
deviations are entered into a radiotherapy incident reporting database.
Supervisors use an in-house Event Analysis System (EASy) to discuss incidents
with staff. Major incidents are analyzed with an in-house Fault Tree Analysis
(FTA). A meta-Analysis is performed using association, text mining, key word
clustering, and differential frequency analysis. A key operating principle
encourages the creation of forcing functions via rapid application development.
RESULTS: 504 events have been logged this past year. The results for the key word
analysis indicate that the root cause for the top ranked key words was
miscommunication. This was also the root cause found from association analysis,
where 24% of the time that an event involved a physician it also involved a
nurse. Differential frequency analysis revealed that sharp peaks at week 27 were
followed by 3 major incidents, two of which were dose related. The peak was
largely due to the front desk which caused distractions in other areas. The
analysis led to many PI projects but there is still a major systematic issue with
the use of forms. The solution we identified is to implement Smart Forms to
perform error checking and interlocking. Our first initiative replaced our daily
QA checklist with a form that uses custom validation routines, preventing
therapists from proceeding with treatments until out of tolerance conditions are
corrected. CONCLUSIONS: PITSTOP has increased the number of quality initiatives
in our department, and we have discovered or confirmed common underlying causes
of a variety of seemingly unrelated errors. It has motivated the replacement of
all forms with smart forms.
PMID- 28517827
TI - SU-E-T-163: Thin-Film Organic Photocell (OPV) Properties in MV and KV Beams for
Dosimetry Applications.
AB - PURPOSE: To characterize dosimetric properties of low-cost thin film organic
based photovoltaic (OPV) cells to kV and MV x-ray beams for their usage as large
area dosimeter for QA and patient safety monitoring device. METHODS: A series of
thin film OPV cells of various areas and thicknesses were irradiated with MV
beams to evaluate the stability and reproducibility of their response, linearity
and sensitivity to absorbed dose. The OPV response to x-rays of various linac
energies were also characterized. Furthermore the practical (clinical)
sensitivity of the cells was determined using IMRT sweeping gap test generated
with various gap sizes. To evaluate their potential usage in the development of
low cost kV imaging device, the OPV cells were irradiated with kV beam (60-120
kVp) from a fluoroscopy unit. Photocell response to the absorbed dose was
characterized as a function of the organic thin film thickness and size, beam
energy and exposure for kV beams as well. In addition, photocell response was
determined with and without thin plastic scintillator. RESULTS: Response of the
OPV cells to the absorbed dose from kV and MV beams are stable and reproducible.
The photocell response was linearly proportional to the size and about slightly
decreasing with the thickness of the organic thin film, which agrees with the
general performance of the photocells in visible light. The photocell response
increases as a linear function of absorbed dose and x-ray energy. The sweeping
gap tests performed showed that OPV cells have sufficient practical sensitivity
to measured MV x-ray delivery with gap size as small as 1 mm. CONCLUSIONS: With
proper calibration, the OPV cells could be used for online radiation dose
measurement for quality assurance and patient safety purposes. Their response to
kV beam show promising potential in development of low cost kV radiation
detection devices.
PMID- 28517828
TI - SU-E-T-201: Safety-Focused Customization of Treatment Plan Documentation.
AB - PURPOSE: Plan report documentation contains numerous details about the treatment
plan, but critical information for patient safety is often presented without
special emphasis. This can make it difficult to detect errors from treatment
planning and data transfer during the initial chart review. The objective of this
work is to improve safety measures in radiation therapy practice by customizing
the treatment plan report to emphasize safety-critical information. METHODS:
Commands within the template file from a commercial planning system (Eclipse,
Varian Medical Systems) that automatically generates the treatment plan report
were reviewed and modified. Safety-critical plan parameters were identified from
published risks known to be inherent in the treatment planning process. Risks
having medium to high potential impact on patient safety included incorrect
patient identifiers, erroneous use of the treatment prescription, and incorrect
transfer of beam parameters or consideration of accessories. Specific examples of
critical information in the treatment plan report that can be overlooked during a
chart review included prescribed dose per fraction and number of fractions, wedge
and open field monitor units, presence of beam accessories, and table shifts for
patient setup. RESULTS: Critical information was streamlined and concentrated.
Patient and plan identification, dose prescription details, and patient
positioning couch shift instructions were placed on the first page. Plan
information to verify the correct data transfer to the record and verify system
was re-organized in an easy to review tabular format and placed in the second
page of the customized printout. Placeholders were introduced to indicate both
the presence and absence of beam modifiers. Font sizes and spacing were adjusted
for clarity, and departmental standards and terminology were introduced to
streamline data communication among staff members. CONCLUSIONS: Plan reporting
documentation has been customized to concentrate and emphasize safety-critical
information, which should allow for a more efficient, robust chart review
process.
PMID- 28517829
TI - SU-E-T-174: Synopsis of the Experimental and Monte Carlo Calculated Values of the
Radial EPOM Shift of Cylindrical Ionization Chambers for Photon-Beam Dosimetry.
AB - PURPOSE: According to the concept of the effective point of measurement (EPOM),
the values of depth z serving as the variable of photon-beam depth dose
distributions in water measured with cylindrical ionization chambers are commonly
corrected according to the formula zeff=zR+?z, were zeff is the depth of the
EPOM, zR the depth of the reference point of the chamber, i.e. of its symmetry
axis, and Az the EPOM shift. Agreed-upon values of the EPOM shift are for
instance ?z=-0.6r (IAEA TRS 398, 2000) and ?z=-0.5r (DIN6800-2,2008) with
r=radius of the air-filled volume. The EPOM concept holds in the falling as well
as in the rising curve branch. The Az versus r relationship is currently
reviewed. METHODS: Measurements of the EPOM shift of cylindrical ionization
chambers for 6/15 MV photons had been based upon a comparison with depth
dependent dose distributions in water measured with the Roos chamber (PTW
Freiburg). Its EPOM position (1.5 mm below the front face) had been determined by
comparison with radiochrome films. (Looe et al, Phys.Med.Biol. 2011;56:4267
4290). Available are also the experimental EPOM shift values by Huang et al,
Physica Medica 2010;26:126-131 and the classical value of Johansson et al, IAEA
SM-222/35,243-270(1978). Accurate Monte Carlo values had been supplied by Tessier
and Kawrakow, Med.Phys. 2010;37:96-107. RESULTS: As shown by the graphical
display of Az versus r, the relationship is nonlinear, shaped as a hockey stick,
with values around -0.2 mm for the "pinpoint" chambers and with values near -1.4
mm for the often-used chambers with radii near 3 mm. For r ranging from 1 to 4
mm, the relationship can be approximated by ?z = -(2.25 mm)*[1-exp(-0.0122 r4)]
with r in mm. CONCLUSIONS: Time has come for a nonlinear updating of the EPOM
shift versus radius relationship of cylindrical ionization chambers applied in
photon-beam dosimetry.
PMID- 28517830
TI - SU-E-T-145: MRI Gel Dosimetry Applied to Dose Profile Determination for 50kV X
Ray Tube.
AB - PURPOSE: The aim of this study was to use MRI gel dosimetry to determine the dose
profile of 50kV MAGNUM(r) X-ray tube, MOXTEK Inc., in order to calibrate small
solid dosimeters of alanine, tooth enamel and LiF-TLDs, commonly used in clinical
quality assurance and datation dosimetry. METHODS: MAGIC-f polymer gel was kept
in two plastic containers of 100mL, avoiding attenuation of the primary beam
trough the wall. Beam aberture of 3mm and dose rate of 16.5Gy/min were set,
reproducing irradiation conditions of interest. The dose rate was assumed based
on data of the vendor information of the tube and dose of 30Gy was delivered at
the surface of the gel. MAGIC-f gel was irradiated at source-surface
distances(SSD) of 0.1cm and 1.0cm. After 24hours of irradiation, gel was scanned
in an Achieva(r) 3T Philips(r) MRI tomography using relaxometry sequence with 32
Echos, Time-to-Echo(TE) of 15.0ms, Time-to-Repetition(TR) of 6000ms and Field-of
View(FOV) of 0.5*0.5*2.0mm. Dose map at the central plain of irradiation was
calculated from T2 relaxometry map. RESULTS: The gel dosimetry results evidenced
a build-up depth of 0.13cm for SSD=0.1cm and no build-up was detected for
SSD=1.0cm. However, the dose profile evidenced high gradient of dose in SSD=0.1,
decreasing the dose from 100% to 30% in 1.4cm depth inside the gel; In turn, the
dose distribution is homogeneous after 0.4cm deth for SSD=1.0cm. CONCLUSIONS: MRI
gel dosimetry using MAGIC-f presented as feasible technique to determine dose
profiles for kilovoltage x-rays tubes. The results evidenced that the calibration
of small solid dosimeters can be performed using SSD of 1.0cm in the 50kV
MAGNUM(r) X-ray tube using 0.4cm/g/cm3 filter. This work was funded supported by
CNPQ, CAPES and FAPESP.
PMID- 28517831
TI - SU-E-T-184: LINAC Commissioning Measurements Utilizing the Cylindrical Arc Check
Phantom.
AB - PURPOSE: New devices for IMRT and VMAT QA are continually becoming available.
Despite the availability of these devices they are underutilized for routine
mechanical QA. In this work we take advantage of the cylindrical geometry of the
Arc Check phantom to perform tests that are an integral part of commissioning and
routine QA. METHODS: The Arc Check is a cylindrical phantom with a diameter of
26.59cm and a 1386 diode array arranged on a cylindrical plane. Owing to its
cylindrical design it is capable of measuring entry and exit radiation. For this
experiment the Arc Check was set up using the mechanical pointer at 86.7cm SSD.
The device was leveled using its inclinometer and was properly rotated to align
with the lasers and cross-hair. With the phantom set up at the expected isocenter
of the LINAC, 100MUs with a 10*10 field were delivered at different gantry
angles, couch and collimator rotations. Each delivery was recorded individually
and for each one the radiation center at the entry and exit levels of the
detector were estimated. That provided the path of the radiation center through
the device. The radiation path was reconstructed for each rotation individually
and the coincidence of the mechanical and radiation isocenter was evaluated.
RESULTS: A procedure and MATLAB routine were developed that accepted as input the
text files that are the output of the Arc Check measurement and geometrically
reconstructed in 3-dimensions the isocenter and radiation central axis for each
rotation. The coincidence of the radiation and mechanical isocenter was verified.
CONCLUSIONS: This work demonstrates that by utilizing the geometry of a
commercially available device multiple mechanical LINAC tests that are part of
routine QA can be evaluated in one single setup.
PMID- 28517832
TI - SU-E-T-156: Robust Algorithms for Correction of Predicted Electronic Portal
Imager Response.
AB - PURPOSE: Predicted electronic portal imaging device (EPID) response, as
calculated by a commercial treatment planning system (TPS), is up to 15% lower
than measured EPID response for off-axis IMRT fields. Two original algorithms are
presented to correct for EPID prediction errors. The EPID prediction algorithm
and a recent image-to-dose conversion algorithm are each tested for ability to
identify TPS dose calculation errors. METHODS: By comparing test images to
respective predictions, correction factors were calculated to modify the EPID
diagonal calibration profile (applied via radial symmetry). Secondly,
image/prediction comparisons were used to compute a 2D correction matrix for EPID
predictions, to account for radially-asymmetric errors. Over 50 IMRT fields of
varying complexity were tested with each correction technique, and with a diode
array. Absolute dose and beam-profile errors were separately induced into the TPS
and a number of IMRT plans were recalculated and measured with three systems - an
EPID prediction system, an EPID image-to-dose conversion system, and a diode
array - for comparison to verification plans. RESULTS: With the profile
correction, TPS predictions agree much better with EPID measurements, yielding
improvement in gamma pass rates (3%,3mm) of over 30% on average for off-axis IMRT
fields. Since off-axis prediction errors are not radially-symmetric, the matrix
correction further improves pass rates by 5% on average (up to 30%) for fields
where the profile correction is limited. The EPID prediction system was unable to
catch either induced TPS error, while both the image-to-dose conversion system
and the diode array indicated both errors. CONCLUSIONS: Profile correction is
effective and efficient though approximate, due to radial symmetry. The matrix
correction is comprehensive but requires computational manipulation of DICOM
images. Users must be aware that EPID prediction systems may be unable to catch
delivered IMRT inaccuracies due to calculation errors downstream from the actual
fluence calculation.
PMID- 28517833
TI - SU-E-T-195: Experience in Implementing Intraoperative Radiation Therapy for
Accelerated Partial Breast Irradiation Using Low-Energy X-Ray Source.
AB - PURPOSE: To present our preliminary experience and quality-assurance (QA)
procedures in implementing intraoperative-radiation therapy (IORT) for
accelerated-partial-breast irradiation (APBI) using the Axxent-system controller
(Xoft Inc.) Methods: IORT was implemented in our institution utilizing a 50-keV x
ray source. APBI allows breast conserving in patients with early-stage-breast
cancer by delivering radiation to the lumpectomy bed via an applicator balloon
filled with water, to which a prescribed dose of 20 Gy was applied to its
surface. In-situ anesthesiology, breast-surgery and radiation-oncology teams were
required to achieve this procedure. Calibration of the source, including
temperature and pressure corrections, was performed by the controller resulting
in a calibration factor, which was manually introduced by a physicist into an in
house program providing the corrected dwell times. Evaluation of exposure
measurements determined that personnel standing behind glass-rolling shields
during irradiation were sufficient protection. RESULTS: We have successfully
treated four patients to date. Surgical times averaged about two hours, QA and
setup of controller took about 30 minutes, while radiation-treatment times ranged
7.8-10.4 minutes. Exposure to personnel showed a negligible dose compared to
background based on the in-vivo measurements. Our measurements have shown that
placement of a shielding layer (FlexiShield) on top of the drape-protected breast
reduced radiation exposure to in-room personnel. In one case, treatment was
automatically stopped by the controller due to a sudden undetected cooling water
flow; due to the pre-treatment training, treatment was successfully resumed
within a minute after manual adjustment of the flow sensor. CONCLUSIONS:
Implementation of IORT to treat patients with APBI using low-energy x-ray source
should follow the manufacturer's recommendations regarding to the acceptance and
personnel training. Our experience indicates that two physicists are necessary at
least at the implementation stage. Appropriate training to deal with potential
problems is crucial before clinical treatment can be ready.
PMID- 28517835
TI - SU-E-T-177: Deconvolution of Line Dose Profiles with Ionization Chambers -
Experiences with the First Software Implementation in Mephisto 3.0.
AB - PURPOSE: To evaluate the first implementation of a deconvolution algorithm in a
commercial water phantom scanning software. METHODS: Line dose profile
measurements in a water phantom are an essential part of a quality assurance
system and in base data measurements in radiotherapy. Usually these measurements
are performed with waterproof ionization chambers of various sizes. These dose
profile measurements are broadened by the Gaussian response functions of the
detectors. In recent studies we showed that the undisturbed line dose profiles
can be reconstruced by iterative deconvolution of the measured signal profiles
with the Gaussian detector response functions. Recently, the proposed method was
implemented in Mephisto 3.0. In this work we analyze the applicability and the
limits of the deconvolution algorithm for several chambers by comparing the
result with diode measurements. RESULTS: As long as the dose gradient becomes not
too steep the deconvolution algorithm is able to reconstruct the undisturbed dose
profiles with sufficient accuracy. Deviations occur for smallest field sizes in
which the width of the detector's lateral response functions reaches the
dimensions of the field. A simple chart for those limits is derived. CONCLUSION:
The implemented deconvolution algorithm allows a fast and simple correction of
measured dose profiles broadened by the volume effect of the ionization chambers.
It offers therefore for the first time a clinical deconvolution of the profiles
on a regular base and by this the implementation of undisturbed base data in the
treatment planning systems as well as in the quality assurance process in modern
radiotherapy.
PMID- 28517834
TI - SU-E-T-167: Comprehensive Evaluation of EPID Image Acquisition for Integrating
and Temporal Dosimetry of Fixed-Gantry IMRT and ArcIMRT.
AB - PURPOSE: To evaluate EPID for dosimetry applications of arc and static-gantry
IMRT with sliding window (SW) and/or step-and-shoot (SS) deliveries Methods: IMRT
beams (SW & SS) were designed that generate beam hold-offs and dose rate
modulation due to MLC motion under 10 * 10 cm jaw. An arcIMRT beam was designed
by adding gantry movement to the SW field. A 10 cm * 10 cm open beam was also
used. Despite differences in delivered dose rates/pulse characteristics, the four
beams should deliver the same total dose. For each beam, various MUs with 6 MV
beam at 300MU/min were irradiated on EPID which operated in image acquisition of
integration mode (IM), continuous scanning mode with synchronization (CMs) and
without (CMn) to beam pulses. Acquired images were evaluated in repeatability,
dose linearity, and reproducibility (reproduce open beam output in IM). RESULTS:
In IM, repeatability, dose linearity, and reproducibility were within 1% for all
dose levels and beams. In CMs, they were within 1-2% if dose rate was maintained
steady (1) for SW beam (needed a minimum 1.3 MU/cm MLC motion) and (2) arcIMRT
beam (needed a minimum 1 MU/degree and 2.8 MU/cm MLC motion) and (3) if a minimum
of 38-40 MU per shoot was used for SS beam. Nonlinearity was observed for fewer
MUs. This is due to the response of EPID to pulse-length reduction for fixed
gantry therapy and pulse dropping for arc therapy. The latter produces in-planar
non-uniformity making EPID unsuitable for temporal dosimetry of arcIMRT.
Sacrifice in temporal resolution then became necessary such as multi-frames per
image (eg. ~1 sec/image). In CMn the results were similar to those of CMs.
However, they showed artifacts, thus this mode was not preferred. CONCLUSIONS: We
found conditions under which integrating and temporal EPID dosimetry can be used
for IMRT and arcIMRT dose deliveries.
PMID- 28517836
TI - SU-E-T-149: Scatter Factors Comparison of 6MV Flattened and 7MV Unflattened
Beams.
AB - PURPOSE: To compare the Collimator scatter factor (Sc), Phantom scatter factor
(Sp) and Total scatter factors (Sc,p) of 6MV flattened Beam (6MV FB) and 7MV
Unflattened beams (7MV UFB). METHODS: The flattening filter and primary
collimator are the major sources of producing the scattered radiation. In this
study, the field sizes from 5*5 cm2 to 40 * 40 cm2 compared for 6MV FB and 7MV
UFB. We measured Sc,p with CC 13 chamber at the depth of 10 g/cm2 using IBA blue
phantom and Sc measured with CC 13 chamber at the depth of 10 g /cm2 using
columnar phantom (TG 74) for 6MV FB and 7MV UFB x-ray beams from a Siemens -
ARTISTE linear accelerator. The Sp values derived from the Sc,p and Sc Values.
RESULTS: All the values of Sc,p, Sc and Sp are normalized to 10 * 10 cm2 field
size the measured values of Sc,p for 6MV FB and 7MV UFB varies from 0.9437 to
1.0651 and 0.9690 to 1.0283 respectively. The Sc values for 6MV FB and 7MV UFB
varies from 0.9676 to 1.0212 and 0.9882 to 1.0075 respectively. The Sp values for
6MV FB and 7MV UFB varies from 0.9752 to 1.0429 and 0.9806 to 1.0206
respectively. Our study results shows that Sc, Sp & Sc,p for 7MV UFB for smaller
fields up to 10 * 10 cm2 were higher than 6MV FB and for larger fields greater
than 10 *10 cm2 it is vice versa. CONCLUSIONS: A scatter factors are measured and
compared for 6MV FB and 7MV UFB. A significant variation observed for Sc, Sp and
Sc,p values of 6MV FB and 7MV UFB .This is may be due to flattening filter and
beam quality.
PMID- 28517838
TI - SU-E-T-160: Response of EBT2 Gafchromic Film to Possible Stresses Associated with
in Vivo Measures.
AB - PURPOSE: to assess the response of EBT2 Gafchromic filmast; to stresses that
might be imposed on the film when used as an in-vivo dosimeter. The following
stress factors were investigated: bending the film; compression; and the shearing
that occurs when cutting the film. METHODS: For bending stress, the film was
rolled into cylinders of various radii, submerged in water, and exposed to X
rays. For compression, 64 cm2 pieces of the film were sandwiched within a stack
of solid water and weights were placed on top of the solid water in order to
compress the film while being exposed to X-rays. For artifacts that arise from
cutting the film, pieces of the film were cut either with scissors or a paper
cutter. The cut film was then exposed uniformly and shearing artifacts introduced
from cutting the film were identified. The effects of 'light piping' from the cut
edges of the film were also investigated. A felt tip pen was used to darken the
cut edges in order to mitigate light piping. The film was scanned with an Epson
10000 XL scanner in transmission mode and images in the red spectrum were
analyzed. RESULTS: At 200 cGy exposures, a compression corresponding to 0.6
kg/cm2 'weight pressure' had less than a 2% influence on the film's response.
Bending the film had a larger influence, >5%, when the radius of curvature was 1
cm. Also, larger artifacts were identified when the film was cut with scissors
and the cut edges were not darkened with a pen. CONCLUSIONS: EBT2 film can
readily be used as an in-vivo dosimeter within the compression and dose ranges
investigated. The user should avoid cutting the film with scissors, and also
avoid excessively bending the film. No COI.
PMID- 28517837
TI - SU-E-T-188: Evaluation of a 3D Patient Relevant Dose QA Tool: Multiple
Institutional Studies.
AB - PURPOSE: To evaluate 3DVHTM as a patient dose-verification and analysis tool
through multiple institutional studies. Virtual patient doses were measured and
compared among different vendors' treatment planning systems (TPS) and delivered
by different vendors' LINACS so that we better understand the uncertainty of
entire process within a patient undergone radiotherapy. METHODS: One head-and
neck (H&N) and one lung patient were selected in this study. The DICOM images/RT
structures along with clinical protocols including prescription doses (59.4Gy for
H&N and 70.2Gy for lung) and normal‐tissues tolerances were distributed to
six institutions. Based on the same criteria, each institution generated their
IMRT plans for the patients. Four different TPS and six different LINACS were
used. The conventional per‐beam IMRT QA using MapCHECK was performed by
all participants. All the measured and calculated data were sent back to one
institution for 3DVH analysis. Through the use of planned-dose-perturbation
(PDP)TM algorithm (Sun Nuclear Corp.), the 'actual-DVHs' were generated and then
compared to the 'reference-DVHs' from plans. Their differences represented errors
induced from the combination of TPS dose-calculation algorithm and beam-delivery
systems. RESULTS: All plans in the study have met the clinical criteria. The 3D
matching rates for 3%global/3mm (DD/DTA) ranged from 95.8-99.9% for H&N and 93.5
100% for lung. The dose-difference-histogram for PTV had a mean of 0.67% [0-2%]
for H&N cases and 1% [0.6-2.8%] for lung cases. The QA tool was able to spot the
doses outside 3%/3mm criteria for critical structures much easier than
conventional planar QA methods. In addition, the hot/cold spots at the boundaries
of collimators are attributed to the uncertainty of collimator-positioning
greater than 1-mm. CONCLUSIONS: The analysis of IMRT plans in this study has
shown that 3DVH is a vital QA tool for assessing clinically relevant doses as
well as diagnosing potential systematic errors from both TPS and delivery
systems.
PMID- 28517839
TI - SU-E-T-171: Missing Dose in Integrated EPID Images.
AB - PURPOSE: A dosimetric artifact has been observed with Varian EPIDs in the
presence of beam interrupts. This work determines the root cause and significance
of this artifact. METHODS: Integrated mode EPID images were acquired both with
and without a manual beam interrupt for rectangular, sliding gap IMRT fields.
Simultaneously, the individual frames were captured on a separate computer using
a frame-grabber system. Synchronization of the individual frames with the
integrated images allowed the determination of precisely how the EPID behaved
during regular operation as well as when a beam interrupt was triggered. The
ability of the EPID to reliably monitor a treatment in the presence of beam
interrupts was tested by comparing the difference between the interrupt and non
interrupt images. RESULTS: The interrupted images acquired in integrated
acquisition mode displayed unanticipated behaviour in the region of the image
where the leaves were located when the beam interrupt was triggered. Differences
greater than 5% were observed as a result of the interrupt in some cases, with
the discrepancies occurring in a non-uniform manner across the imager. The
differences measured were not repeatable from one measurement to another.
Examination of the individual frames showed that the EPID was consistently losing
a small amount of dose at the termination of every exposure. Inclusion of one
additional frame in every image rectified the unexpected behaviour, reducing the
differences to 1% or less. CONCLUSIONS: Although integrated EPID images nominally
capture the entire dose delivered during an exposure, a small amount of dose is
consistently being lost at the end of every exposure. The amount of missing dose
is random, depending on the exact beam termination time within a frame. Inclusion
of an extra frame at the end of each exposure effectively rectifies the problem,
making the EPID more suitable for clinical dosimetry applications. The authors
received support from Varian Medical Systems in the form of software and
equipment loans as well as technical support.
PMID- 28517840
TI - SU-E-T-162: Rapid Assessment of Cyberknife IRIS Variable Collimator Performance
Using a Commercial Diode Array.
AB - PURPOSE: To describe an efficient method for verifying the size and centering of
the radiation field from the Cyberknife IRIS variable collimator with sub
millimeter accuracy using a general purpose commercially available diode array.
METHODS: We present a technique using a conventional diode array (Sun Nuclear
Profiler) with the array at an extended distance of 320 cm. The projection of the
4 mm diode spacing back to the 80 cm field definition distance gives an effective
spacing of 1 mm, sufficient to confirm proper operation of the IRIS. We describe
the data acquisition process and present data comparing the Profiler measurements
to scanned measurements for both profile and FWHM analysis and reproducibility of
the technique over repeated measurements. RESULTS: Average difference between
original water scanner measurements and diode array measurements over the 12
aperture sizes) from 5 mm to 60 mm) were - 0.14 mm (range 0.03 mm to 0.83 mm).
Reproducibility and centering measurements had a similar range of accuracy.
CONCLUSIONS: A general purpose commercially available diode array can be used to
quickly and accurately characterize the field size and centering of the
Cyberknife IRIS variable collimator system with sub-millimeter accuracy
subsequent to service, software recalibration, software upgrades or associated
with routine QA. This technique avoids the time consuming and cumbersome water
tank scanning with a diode and the difficulties associated with image based
measurements (CR or radiochromic film) that require time consuming and careful
calibration and choice of threshold values.
PMID- 28517841
TI - SU-E-T-200: IMRT Patient Specific QA for On-Line Adaptive Radiotherapy.
AB - PURPOSE: On-line adaptive IMRT requires a highly efficient radiotherapy team and
an intensive amount of work, as well as significant amount of Quality Assurance
(QA). With regard to patient specific QA, it is clinically unrealistic to perform
fluence measurements via a QA phantom while patient is setup awaiting treatment.
We therefore developed an alternative way to check point dose and the IMRT
fluence right before beam delivery. METHODS: In this study, 28 IMRT plans were
generated with Prowess Panther 5.1 for three prostate cancer patients on 28 CT
datasets with CTV and critical organs contoured by treating physicians. The
corresponding QA plans were generated by Prowess, and then transfered to Pinnacle
9.2 for fluence recalculation on a flat surface phantom, In addition 28 QA plans
were delivered on a Siemens Artiste accelerator and fluence were measured with
Matrixx IMRT Device. We analyzed both point dose and fluence for these 28
samples. RESULTS: Of all 28 IMRT plans, the point dose difference between Prowess
and Pinnacle are well within 1%. The point dose difference between measurements
and Prowess calculation are all within 3%. The passing rates using gamma criteria
(3%3mm) for the fluence comparison between Prowess and Pinnacle calculation are
at least 98.5% while the passing rates of the gamma analysis between fluence
measurement and Prowess calculation are all better than 98.5%. The passing rate
of gamma difference between Prowess vs Pinnacle and Prowess vs QA measurement is
less than 1.5% for all 28 samples. Therefore, second TPS (e.g. Pinnacle) can be
used to verify planned fluencies and can serve as a valuable patient specific QA
when conventional IMRT QA measurement is not feasible. CONCLUSIONS: A new IMRT
plan is desired if significant anatomy change from the date of original CT scan
is observed before the radiation delivery. It is not clinically feasible to check
the fluence on the machine before radiation delivery while the patient is in the
treatment suite awaiting radiation delivery. Our method showed here is an
alternative way to verify the planned fluence with a second TPS and can serve as
a valuable IMRT patient specific QA in online adaptive radiotherapy.
PMID- 28517842
TI - SU-E-T-173: TomoTherapy Treatment Couch Velocity Verification Using TomoDose.
AB - PURPOSE: Accurate TomoTherapy treatment is dependent on multiple parameters,
including the accuracy of couch velocity during beam delivery and gantry
rotation. The recent TG-148 protocol recommends quarterly film tests to verify
the constancy of couch velocity. We determined the feasibility of using TomoDose,
a quality assurance device, to detect the variation in couch velocity from
baseline by a deviation of one or two percent. METHODS: The TomoDose unit was
rotated 90 degrees clockwise so that the long axis, consisting of 107 detectors,
would translate across the TomoTherapy 'Y' jaws. The collimator field size used
was the 1 cm mode and the table velocity was set to 0.5 mm/sec to establish a
baseline. The velocity was then varied by 1% or 2% from nominal. The five tested
velocities were 0.495, 0.490, 0.500, 0.505 and 0.510 mm/sec. The total
translation time was kept at a constant 400 sec. The field was progressively
painted during the scans and was shortened if table velocity was decreased, and
lengthened as velocity was increased. RESULTS: The baseline field size was 20.03
cm (400 sec * 0.05 cm/sec). A 2% increase in velocity translated to an increase
in the field size to 20.39 cm and a 2% decrease in velocity resulted in a
decrease in field size to 19.64 cm. Similarly, a 1% increase in velocity
increased the field to 20.18 cm, and a 1% decrease velocity decreased the field
to 19.76 cm. CONCLUSIONS: An increase or decrease in the couch velocity, for a
fixed beam delivery time, resulted in an altered radiation field size. The field
size results are approximately as expected for both the baseline scans as well as
the modified velocity scans. This study demonstrates that, under these
conditions, TomoDose can be used to determine small variations in table velocity
as small as 1 %.
PMID- 28517843
TI - SU-E-T-183: Managing and Assessing Patients Receiving Radiotherapy with
Implantable Cardiac Devices.
AB - PURPOSE: To assess the effectiveness of the management of patients with cardiac
electronic implantable devices (CEIDS) receiving radiotherapy. METHOD AND
MATERIALS: In 2005, a formal communication process was established between
Radiation Oncology and Cardiac Electrophysiology (EP) for the management of
patients with permanent, implantable cardiac devices receiving radiotherapy. The
process requires a pre-treatment consult with EP. This information is provided to
a medical physicist, who works with the primary radiation oncologist and
dosimetrist. Based on the estimated dose to the device, EP and Radiation Oncology
will determine the appropriate oversight required for treatment. To assess the
effectiveness of this program, a retrospective analysis of patients with
implantable cardiac devices receiving radiotherapy between the years 2005 and
2011 was performed. RESULTS: Sixty-nine patients with CEIDs (19 implantable
cardioverter defibrillators (ICDs) and 50 pacemakers) were treated in Radiation
Oncology between 2005 and 2011. Patients were treated to a variety of sites,
including 21 patients treated to multiple sites. Doses were estimated prior to
radiotherapy, and in vivo measurements were obtained for patients near or
exceeding our institutional device tolerance (ICDs = 1 Gy and ICPs = 2 Gy), or if
the device was less than 10 cm from the edge of a treatment field. Of the
patients evaluated, there were only two patients with ICD devices which had a
partial reset of diagnostic data during their treatment. There were no major
device failures of arrhythmia detection or treatment. CONCLUSIONS: Our multi
disciplinary team has worked together to develop a process to manage the care of
patients with permanent implantable cardiac devices. There have been few device
events noted in our patient cohort. The team will continue to follow our
institutional management methodology to assess the appropriate amount of EP care
necessary during radiation therapy. Laura Horwood is on the speakers bureau for
Medtronic. Frank Pelosi is on the advisory board for Boston Scientific Corp and
St. Jude Medical, is receiving an educational grants from Medtronic, St Jude,
Boston Scientific, Biotronik, and a research grants from Medtronic.
PMID- 28517844
TI - SU-E-T-155: Dose Response Curve of EBT2 and EBT3 Radiochromic Films to a
Synchrotron-Produced Monochromatic X-Ray Beam.
AB - PURPOSE: This work investigates the dose-response curves of Gafchromic EBT2 and
EBT3 radiochromic films using synchrotron-produced monochromatic x-ray beams.
These dosimeters are being utilized for dose verification in photoactivated Auger
electron therapy at the LSU Center for Advanced Microstructures and Devices
(CAMD) synchrotron facility. METHODS: Monochromatic beams of 25, 30 and 35 keV
were generated on the tomography beamline at CAMD. Ion chamber depth-dose
measurements were used to calculate the dose delivered to films irradiated
simultaneously at depths from 0.7 - 8.5 cm in a 10*10*10-cms
polymethylmethacrylate phantom. AAPM TG-61 protocol was applied to convert
measured ionization into dose. Calibrations of films at 4 MV were obtained for
comparison using a Clinac 21 EX radiotherapy accelerator at Mary Bird Perkins
Cancer Center. Films were digitized using an Epson 1680 Professional flatbed
scanner and analyzed using the optical density (OD) derived from the red channel.
RESULTS: For EBT2 film the average sensitivity (OD/dose) at 50, 100, and 200 cGy
relative to that for 4-MV x- rays was 1.07, 1.20, and 1.23 for 25, 30, and 35
keV, respectively. For EBT3 film the average sensitivity was within 3 % of unity
for all three monochromatic beams. CONCLUSIONS: EBT2 film sensitivity shows
strong energy dependence over an energy range of 25 keV - 4 MV. EBT3 film shows
weak energy dependence, indicating that it would be the better dosimeter for
Auger electron therapy. This research was supported by contract W81XWH-10-1-0005
awarded by The U.S. Army Research Acquisition Activity, 820 Chandler Street, Fort
Detrick, MD 21702-5014. This report does not necessarily reflect the position or
policy of the Government, and no official endorsement should be inferred.
PMID- 28517845
TI - SU-E-T-194: Evaluation and Simulation of Shallow Depth Skin Dose from Couch Top
in Radiotherapy.
AB - PURPOSE: When the treatment couch-top contacts the patient, the skin dose to the
patient also generates clinical significance as the radiation beam passes through
the couch. In this study, the effect on entrance shallow depth dose was
investigated for the carbon fiber exact couch-top from Varian Medical System.
METHODS: An Accredited Dosimetry Calibration Laboratory (ADCL) calibrated PTW
parallel-plate thin-window chamber was used to measure the doses in the build-up
region. Firstly, the shallow depth doses at different field sizes, depths and
incident angle beams were measured for 6MV and 18MV photon beams. To test the
couch top contribution to the dose distribution, the depth of measurement went
down to 10cm. The couch was simulated in the Eclipse treatment planning system
and the related point dose was calculated with different depths. The CT number of
the couch top was adjusted to generate agreement between measurement and
simulation. RESULTS: At a 2mm depth, the surface dose increased with the decrease
of the field size. Comparing with and without the couch top, as field sizes vary
from 20cm*20cm to 2cm*2cm, the dose increased from 35% to 53% of for 6MV, and
from 50% to 113% for 18MV. At 0mm depth, the dose difference was most significant
and is at the level of 300%. Angle incident beam dose increase due to couch top
varied with complicated dose distribution. Extended Depth Dose measurement shows
that couch top effect on dose in build-up region extends to depths of 1cm for 6MV
and 2cm for 18MV. An appropriate CT number setting of the couch top is between
200HU to -300HU. CONCLUSIONS: The couch simulation in Eclipse displays better
dosimetric accuracy in couch contacted skin dose. However, calculation factors
such as surface definition, heterogeneity, calculation resolution and algorithm
also need extra consideration.
PMID- 28517846
TI - SU-E-T-166: Use of an in Vivo Dosimeter to Assess the Implications of Daily
Prostate Rotations.
AB - PURPOSE: It is well established that using image guidance for prostate motion
allows reduction of margin, dose escalation, decreased toxicity and recently
improved outcomes. However, current methods only account for translational
motion, not rotational variations. The purpose of this study is to assess whether
rotations in anatomy lead to significant changes in the delivered dose for
prostate patients. METHODS: Under an IRB approved protocol, 11 consecutive
patients underwent prostate IMRT using IGRT with implanted metal-oxide
semiconductor field-effect transistors (MOSFETs); the Dose Verification System
(DVS) manufactured by Sicel Technologies. Two dosimeters were implanted per
patient. From conebeam CT (CBCT) registration, corrections were applied to all
translational errors. For rotations larger than 3 degrees, patient were
repositioned and realigned to attempt to correct the rotation. Both translational
and rotational errors based on the CBCT were documented. The daily DVS readings
were compared to CBCT rotations about each axis (pitch, roll and yaw) and the
root-mean square (RMS) rotation. RESULTS: 372 CBCT images were acquired. The
correlation between rotation and DVS measurement was analyzed using linear
regression. The R2 value for pitch was 0.059 and 0.144 for each dosimeter,
respectively. For roll, the R2 values were 0.049 and 0.001. For yaw, the values
were <0.001. For the RMS rotation, R2 was 0.034 and 0.038. As it could confound
results, the angular dependence of the dosimeters was measured during
commissioning and found that it was approximately 0.5% for 5 degree rotations.
CONCLUSIONS: We did not find any significant correlation between prostate
rotation around any axis and discrepancy in DVS reading. These results show that
rotations seen clinically do not have a substantial effect on the dose delivered
to the prostate. Further studies will attempt to determine at what angle
rotations begin to affect the dose distribution, if at all.
PMID- 28517847
TI - SU-E-T-204: A Prototype of Dose-Guided Radiation Therapy.
AB - PURPOSE: With the advancement in dosimetric devices and the development of dose
reconstruction algorithm, the implementation of dose-guided radiation therapy
(DGRT) is feasible. In order for DGRT to be performed clinically, a prototype of
DGRT was developed in this study. METHODS: The prototype adopted a strategy for
DGRT that adjusted the treatment plan for future fractions to compensate for
dosimetric errors from past fractions, which included four main functional
modules: management of patient plan information, dose reconstruction, dose
evaluation, plan adjustment. we developed our dose reconstruction procedure,
including the dosimetric calibration of the portal image acquired using
electronic portal image device (EPID) during treatment and three-dimensional (3D)
patient dose reconstruction based on Monte Carlo Finite-size pencil beam (MCFSPB)
model and Conjugate-gradient (CG) algorithm developed by FDS Team
(www.fds.org.cn). The dose evaluation tools including 3D Gamma analysis and dose
volume-histogram (DVH) analysis were also available which were used to compare
the reconstruction dose with the planning dose. Finally we re-optimizing the
treatment plan according to the information provided by dose evaluation. RESULTS:
In order to validate the availability of the workstation prototype, lots of
experiments were carried out based on head phantom. The result showed that
disagreement between the reconstructed dose and the planning dose (calculated by
the Accurate Radiotherapy System (ARTS) developed by FDS Team) was observed by
the DGRT prototype when there existed position error for head phantom or the
accelerator delivery was not accurate. CONCLUSIONS: An effective prototype for
DGRT has been developed. With these techniques, the clinical implementation of
DGRT is possible in the near future. Supported by the National Natural Science
Foundation under grant No.30900386 and the National Science Foundation of Anhui
Province (Nos.090413095 and 111040606Q55).
PMID- 28517848
TI - SU-E-T-176: Improved Collimator Scattering Factor (Sc) Measurements for Small
Fields Using Build-Up Caps in Robotic Radiosurgery.
AB - PURPOSE: The Monte Carlo calculation algorithm in the MultiPlan (Accuray, Palo
Alto, CA) treatment planning system used for CyberKnife (Accuray) robotic
radiosurgery requires in-air measurements. In this study, results were compared
for the impact of build-up caps using a diode detector for small field in-air
measurements. METHODS: Two acrylic caps custom-made for the SFD diode detector
(IBA, Germany) of two thicknesses were compared against free-in-air measurements.
The 1.5 and 5 cm thicknesses correspond to Dmax and a depth beyond the range of
electron contamination, respectively. A Blue Phantom (IBA) was used to position
the diode 80 cm SAD. Measurements were made for all 12 fixed cones ranging from 5
to 60 mm. RESULTS: For the 5 mm cone, there is a 15.6% and 20.0% difference in
the Sc factor between the 1.5 cm and 5 cm buildup caps, respectively, versus the
free-in-air measurement. For the 7.5 mm cone, the difference is 6.3% and 10.4%
for the 1.5 cm and 5 cm buildup caps, respectively, versus the free-in-air
measurement. While generally decreasing, the Sc factor for either buildup cap
does not agree within 2% to free-in-air measurements until the cone used is
larger than 40 mm. Overall, the two buildup caps yield similar Sc factors and the
differences observed are attributed to electron contamination. CONCLUSIONS: The
Monte Carlo calculation algorithm used by the CyberKnife planning manual does not
refer to any build-up caps. This study has shown that, particularly for small
fields, there are large differences in Sc factors measured with and without
buildup caps. In general, for fields smaller than 10 mm, build-up caps should be
carefully chosen, especially in commissioning data.
PMID- 28517849
TI - SU-E-T-148: An Optimizing Study of a New Multi Channel Virginal Cylinder
Applicator in Brachytherapy.
AB - PURPOSE: A new CT/MRI vaginal multichannel applicator was introduced by
Elekta/Nucletron(r) recently. The multi-lumen cylindrical device intends to
improve and optimize treatment of local advanced vaginal cancer. The design of
this applicator includes several inner peripheral channels in equal spacing
isotropically 5 mm from the surface of cylinder. The central tube provides the
unique function as it was in traditional single channel treatment. METHODS:
Ninteen CT image sets of six patients were taken with multichannel applicator
inserted. The single channel plan was planned before multichannel plan to justify
the dose coverage to the prescribed volume and the doses received by bladder and
rectum. The Oncentra(r) Brachytherapy planning system was employed to generate
forward plan in single channel and inverse plan in multichannel where doses to
bladder and rectum were evaluated and weighted by using Inverse Planning
Simulated Annealing (IPSA) algorithm. RESULTS: Figure.1 shows plan Result from
single channel and Figure.2 shows multichannel Result with IPSA. The comparison
confirms multichannel provides better coverage of V90, V95 and V100 to the
prescribed 5 mm vaginal cuff rind. The maximal doses delivered to bladder and
rectum were reduced and the mean dose was lowered in average by 5-9% and 7-11%
respectively. CONCLUSIONS: The nature of Brachytherapy is to take advantages of
short fall off of radiation dose outside the intended treated tumor and minimize
dose to surrounding tissues and critical organs. However treatment technique and
plan optimization could be improved and be enhanced to benefit cancer treatment
from advanced design of the applicators. This study demonstrates a new
multichannel applicator affords promising conformal treatment to the tumor and
liberates the doses to the critical structures by using optimization to meet our
objectives.
PMID- 28517850
TI - SU-E-T-159: Sensitivity of in Line Real Time Scintillating Fiber Detectors for
External Beam Treatment Verification and Patient Safety.
AB - PURPOSE: We studied the sensitivity of a novel transmission fiber scintillator
array designed and built for in line treatment verification. The purpose of this
project is to assess the capability of the fiber detector array technology to
detect treatment errors in real time without false positives to enhance patient
safety. METHODS: We developed a linear scintillator array detector using
radiation hard scintillating fibers and high speed parallel signal conditioning
and data acquisition to monitor external beam treatment fluence in real time. The
detector captures and resolves the time and amplitude of each linac pulse at each
MLC segment. The detector has 60 fibers aligned to each MLC leaf and two output
channels per fiber. The data is captured by a high speed parallel digitizer to
determine the IMRT beam output delivered to a patient in real time. We evaluated
the detector peak pulse linearity according to dose rate, MLC positioning, and
beam energy. We analyzed the detector sensitivity, signal to noise ratio, and
pulse distribution statistics to determine beam output and fluence in real time.
RESULTS: We analyzed the response of the detector to 6 MV and 10 MV photon beams.
The statistical analysis of the detected linac pulses indicates that a minimum of
20 pulses are required to evaluate MLC positioning and fluence with 3 mm and 3%
resolution, respectively. During testing, no false positives were detected.
Linearity with respect to output rate, MLC or jaw opening, and fluence is within
2%. CONCLUSIONS: Measured sensitivity and signal to noise ratio of a real time
linear fiber array detector show that delivered beam fluence can be monitored
every 55 msec, with no observed false positives during treatment to provide in
vivo real time patient safety and beam monitoring.
PMID- 28517851
TI - SU-E-T-198: Patient Scheduling Monitor (PSM)-A New Tool for Radiation Therapy
Patient Scheduling and Workflow Management in an Increasingly Digital
Environment.
AB - PURPOSE: To develop an easy-to-use and customizable Patient Scheduling Monitor
for 1) active monitoring of radiation therapy workflow from CT simulation to the
start of treatment and 2) for optimizing the workflow based on treatment
complexity. METHODS: Microsoft Access database and Visual Basic language were
used to create an in-house software application, Patient Scheduling Monitor
(PSM). The PSM was designed with three functional modules: a patient schedule
calculator, a workflow progress tracker, and a workflow evaluator. The PSM
divides the radiation treatment workflow into 6 tasks including image
acquisition/fusion, target delineation, dosimetry planning, MD review, physics QA
and RTT QA. On the day of CT simulation, the scheduling calculator generates a
planned timeline for each task based on the CT-simulation date and the default
standard established for each given task and treatment type. Each task within the
PSM can also be individualized as needed. After simulation, the progress tracker
enables staff to actively monitor the workflow. The workflow evaluator will query
the database and analyze the planned versus actual timeline and provide data for
future workflow analysis. RESULTS: We have used the PSM since Nov, 2011 for 186
patients. The PSM has allowed us to provide patient start times at the completion
of simulation. It has helped to improve patient satisfaction. The workflow
progress tracker enabled us to actively manage the workflow. Currently, for
patients managed using the PSM, no rescheduling has been required. The use of PSM
has reduced the average CT simulation to treatment start times. It also has
improved intradepartmental communications. CONCLUSIONS: An easy-to-use patient
scheduling monitor has been developed. The PSM has been shown to be an efficient
and effective tool in managing, assessing and improving the radiation therapy
workflow and will be useful in managing the timelines in an increasingly dynamic
working environment.
PMID- 28517911
TI - Is there a potential of misuse for Magnolia officinalis compounds/metabolites?
AB - OBJECTIVE: Magnolia bark contains magnolol, metabolized to tetrahydromagnolol and
honokiol, with both GABA-ergic/cannabimimetic activities, hence of possible
attraction to vulnerable individuals/recreational misusers. METHODS: A literature
review, assessment of related anecdotal online Magnolia misuse's reports and an
overview of Magnolia products' online acquisition possibilities has been here
described. RESULTS: No peer-reviewed papers about Magnolia
abuse/misuse/dependence/addiction were identified. Conversely, from a range of
websites emerged potentially 3 groups of Magnolia misusers: (a) subjects with a
psychiatric history already treated with benzodiazepines, being attracted to
Magnolia bark as a "natural sedative"; (b) polydrug misusers, ingesting Magnolia
with a range of other herbs/plants, attracted by the GABA-ergic/cannabimimetic
activities; (c) subjects naive to the misusing drugs' scenario, perceiving
Magnolia as a natural dietary supplement/weight-control compound. CONCLUSIONS: To
the best of our knowledge, this is the first paper commenting on the possible
Magnolia derivatives' potential of misuse. Magnolia's recent increase in
popularity, mainly as a sedative, may be arguably due to its peculiar
pharmacological properties/acceptable affordability levels/virtually worldwide
favorable legal status and customers' attraction to a product being perceived as
"natural" and hence somehow "safe." Future/potent/synthetic magnolol and honokiol
structural analogues could however contribute to increasing the number of
synthetic GABA-ergic/cannabimimetic misusing compounds.
PMID- 28517912
TI - Keeping good friends close - The surface and secreted proteomes of a probiotic
bacterium provide candidate proteins for intestinal attachment and communication
with the host.
AB - Bacteria use cell surface proteins and secreted proteins to interact with host
tissues. Several dozen previously published proteomics studies have identified
cell surface proteins for pathogens. In this issue, Celebioglu and Svensson
(Proteomics 2017, 17, 1700019) use 2D gel electrophoresis and mass spectrometry
to identify secreted and cell surface proteins of a commensual gut bacterium,
Lactobacillus acidophilus NCFM. Some of the proteins are known to have functions
in the cytoplasm, and their presence on the cell surface suggests they might be
moonlighting proteins. In addition, comparisons of proteins used by pathogenic
and probiotic species to interact with their hosts could lead to improved
treatments of infections and chronic diseases that are associated with an
imbalance of pathogenic and probiotic gut bacteria.
PMID- 28517913
TI - Sodium-glucose co-transporter-2 inhibitors and diabetic ketoacidosis: An updated
review of the literature.
AB - Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are increasingly used for the
treatment of type 2 diabetes (T2D) and can improve glucose control also in type 1
diabetes (T1D). In May 2015, regulatory agencies issued a warning that SGLT2is
may cause diabetic ketoacidosis (DKA). We report details on 2 new cases of SGLT2i
associated DKA and review the literature for similar cases within randomized
controlled trials (RCTs), cohort studies and single reports. We searched the
medical literature for reports of SGLT2i-associated DKA cases. A quantitative
analysis of frequency and clinical characteristics is reported. The 2 narrative
cases illustrate that SGLT2i-associated DKA can occur in patients with T1D
incorrectly diagnosed as T2D, perhaps without the presence of obvious DKA
precipitating factors. The incidence of SGLT2i-associated DKA was less than
1/1000 in randomized controlled trials and 1.6/1000 person-years in cohort
studies. We retrieved detailed data on 105 SGLT2i-associated DKA case reports,
wherein 35% showed glucose levels of less than 200 mg/dL and 22% were not
associated with typical triggers. In case reports and in pharmacovigilance
databases, duration of SGLT2i treatment before DKA onset was extremely variable.
Fatal SGLT2i-associated DKA episodes were found only in pharmacovigilance
databases and represented 1.6% of all reported cases. DKA is a rare adverse event
during SGLT2i therapy. Predisposing and precipitating factors are still
incompletely understood, although a minority of cases lacked typical DKA
triggers. More narrative case series and cohort studies are needed to better
understand the true risk and the spectrum of this adverse event.
PMID- 28517914
TI - Osimertinib in EGFR T790M-Positive Lung Cancer.
PMID- 28517915
TI - Microbial Glycosylation of Flavonoids.
AB - Flavonoids constitute a large group of polyphenolic compounds naturally found in
plants, which have a wide range of biological activity. Although flavonoids are
beneficial to human health, their application is limited by their low
bioavailability and poor water-solubility. Therefore, recently there has been a
particular interest in glycosylated forms of flavonoids, which usually are better
soluble, more stable, and more functional compared to their aglycones. Microbial
transformation of natural flavonoids may be an attractive way of receiving their
glycosylated derivatives in amounts sufficient for the research on the effect of
glycoside group on compound properties and for further application of these
compounds as ingredients of dietary supplements and pharmaceuticals.
PMID- 28517916
TI - Relationship between ureB Sequence Diversity, Urease Activity and Genotypic
Variations of Different Helicobacter pylori Strains in Patients with Gastric
Disorders.
AB - Association of the severity of Helicobacter pylori induced diseases with
virulence entity of the colonized strains was proven in some studies. Urease has
been demonstrated as a potent virulence factor for H. pylori. The main aim of
this study was investigation of the relationships of ureB sequence diversity,
urease activity and virulence genotypes of different H. pylori strains with
histopathological changes of gastric tissue in infected patients suffering from
different gastric disorders. Analysis of the virulence genotypes in the isolated
strains indicated significant associations between the presence of severe active
gastritis and cagA+ (P = 0.039) or cagA/iceA1 genotypes (P = 0.026), and
intestinal metaplasia and vacA m1 (P = 0.008) or vacA s1/m2 (P = 0.001)
genotypes. Our results showed a 2.4-fold increased risk of peptic ulcer (95% CI:
0.483-11.93), compared with gastritis, in the infected patients who had dupA
positive strains; however this association was not statistically significant. The
results of urease activity showed a significant mean difference between the
isolated strains from patients with PUD and NUD (P = 0.034). This activity was
relatively higher among patients with intestinal metaplasia. Also a significant
association was found between the lack of cagA and increased urease activity
among the isolated strains (P = 0.036). While the greatest sequence variation of
ureB was detected in a strain from a patient with intestinal metaplasia, the sole
determined amino acid change in UreB sequence (Ala201Thr, 30%), showed no
influence on urease activity. In conclusion, the supposed role of H. pylori
urease to form peptic ulcer and advancing of intestinal metaplasia was postulated
in this study. Higher urease activity in the colonizing H. pylori strains that
present specific virulence factors was indicated as a risk factor for promotion
of histopathological changes of gastric tissue that advance gastric malignancy.
PMID- 28517917
TI - Interaction of Gram-Positive and Gram-Negative Bacteriawith Ceramic Nanomaterials
Obtained by Combustion Synthesis - Adsorptionand Cytotoxicity Studies.
AB - This paper presents the interactions of Gram-positive (Staphylococcus aureus) and
Gram-negative (Pseudomonas putida) bacteria with ceramic materials obtained by
combustion synthesis. These studies were conducted based on an analysis of the
adsorption of bacteria onto aggregates of ceramic materials in an aqueous
suspension. The materials used in the studies were of a nanostructured nature and
consisted mainly of carbides: silicon carbide (SiC) in the form of nanofibers
(NFs) and nanorods (NRs), titanium carbide, and graphite, which can also be
formed by combustion synthesis. Micrometric SiC was used as a reference material.
Gram-positive bacteria adsorbed more strongly to these materials. It seems that
both the point of zero charge value and the texture of the ceramic material
affected the bacterial adsorption process. Additionally, the viability of
bacteria adsorbed onto aggregates of the materials decreased. Generally, P.
putida cells were more sensitive to the nanomaterials than S. aureus cells. The
maximum loss of viability was noted in the case of bacteria adsorbed onto NRSiC
and NFSiC aggregates.
PMID- 28517918
TI - Biocontrol of Gray Mold Decay in Pear by Bacillus amyloliquefaciens Strain BA3and
its Effect on Postharvest Quality Parameters.
AB - The economic losses caused by postharvest fruits diseases have attracted global
attention. Traditional chemical fungicide could not meet the need of humans. In
recent years, microbial agent which has begun to take the place of chemical
fungicide comes into people's vision. The aim of this paper was to investigate
the potential of Bacillus amyloliquefaciens strain BA3 for its biocontrol
capability on gray mold decay of pears and its effect on postharvest quality of
pears. Compared with other treatments, the inhibition effect on gray mold of
washed cell suspension of B. amyloliquefaciens was the best. Consequently it was
utilized in subsequent experiments. Spore germination and germ tube length of
Botrytis cinerea was 18.72% and 12.85 MUm treated with BA3, while the control
group was 62.88% and 30.44 MUm. We confirmed that increase of the concentration
of B. amyloliquefaciens, improved the efficacy of BA3 in controlling gray mold
decay of pears. Colonization variation of BA3 in wounds of pears was recorded. To
begin with, the populations of B. amyloliquefaciens increased rapidly and
remained stable. On the fourth day, there was a declining trend , after that the
population increased to 4 * 10(5) CFU/wound and remained stable. BA3 had no
significant effect on mass loss, titratable acidity, firmness and total soluble
solids of pears that were stored at 25 degrees C for 7 days comparing with
control group. However, the effect of B. amyloliquefaciens on ascorbic acid was
significantly higher than that of the control group. Our study indicates that B.
amyloliquefaciens has a potential as postharvest biocontrol agent on pears.
PMID- 28517919
TI - Enzymes Involved in Naproxen Degradation by Planococcus sp. S5.
AB - Naproxen is a one of the most popular non-steroidal anti-inflammatory drugs
(NSAIDs) entering the environment as a result of high consumption. For this
reason, there is an emerging need to recognize mechanisms of its degradation and
enzymes engaged in this process. Planococcus sp. S5 is a gram positive strain
able to degrade naproxen in monosubstrate culture (27%). However, naproxen is not
a sufficient growth substrate for this strain. In the presence of benzoate, 4
hydroxybenzoic acid, 3,4-dihydroxybenzoic acid or vanillic acid as growth
substrates, the degradation of 21.5%, 71.71%, 14.75% and 8.16% of naproxen was
observed respectively. It was shown that the activity of monooxygenase,
hydroxyquinol 1,2-dioxygenase, protocatechuate 3,4-dioxygenase and
protocatechuate 4,5-dioxyegnase in strain S5 was induced after growth of the
strain with naproxen and 4-hydroxybenzoate. Moreover, in the presence of naproxen
activity of gentisate 1,2-dioxygenase, enzyme engaged in 4-hydroxybenzoate
metabolism, was completely inhibited. The obtained results suggest that
monooxygenase and hydroxyquinol 1,2-dioxygenase are the main enzymes in naproxen
degradation by Planococcus sp. S5.
PMID- 28517920
TI - Characterization of Bacteria Isolation of Bacteria from Pinyon
Rhizosphere,Producing Biosurfactants from Agro-Industrial Waste.
AB - Two hundred and fifty bacterial strains were isolated from pinyon rhizosphere and
screened for biosurfactants production. Among them, six bacterial strains were
selected for their potential to produce biosurfactants using two low cost wastes,
crude glycerol and lactoserum, as raw material. Both wastes were useful for
producing biosurfactants because of their high content in fat and carbohydrates.
The six strains were identified by 16S rDNA with an identity percentage higher
than 95%, three strains belonged to Enterobacter sp., Pseudomonas aeruginosa,
Bacillus pumilus and Rhizobium sp. All strains assayed were able to grow and
showed halos around the colonies as evidence of biosurfactants production on
Cetyl Trimethyl Ammonium Bromide agar with crude glycerol and lactoserum as
substrate. In a mineral salt liquid medium enriched with both wastes, the
biosurfactants were produced and collected from free cell medium after 72 h
incubation. The biosurfactants produced reduced the surface tension from 69 to 30
mN/m with an emulsification index of diesel at approximately 60%. The results
suggest that biosurfactants produced by rhizosphere bacteria from pinyon have
promising environmental applications.
PMID- 28517921
TI - Levels of Organic Compounds, Number of Microorganismsand Cadmium Accumulation in
Festuca ovina Hydroponic Culture.
AB - Understanding the microbiological, biochemical and physiological aspects of
phytoremediation of soil and water environments polluted to different degrees
with heavy metals has very important theoretical and practical implications. In
this study, a comparison was made between total cadmium concentration in root and
shoot tissues as well as concentrations of particular fractions of Cd immobilized
by roots of Festuca ovina (Sheep's fescue) hydroponically cultivated in nutrient
solutions supplemented with 1 MUg Cd ml(-1) and those cultivated at 10 MUg Cd ml(
1). After three weeks of F. ovina cultivation, the number of bacterial CFU and
the amounts of organic chelators, siderophores, proteins and reducing sugars in
the growth medium and on the root surface were higher at 10 than at 1 MUg Cd ml(
1). The grass also reacted to the high Cd concentration by a decrease in plant
growth and dehydrogenase activity in root tissues. The concentration of Cd
determined in fractions bound with different strength in roots was significantly
dependent on Cd concentration in the growth medium. When the plants were grown at
1 MUg Cd ml(-1), 9% of the immobilized cadmium was loosely bound to the root
surface, 20% was exchangeable adsorbed, and 28% was bound by chelation; at 10 MUg
Cd ml(-1), the respective values were 12%, 25%, and 20%. About 43% of the
immobilized cadmium remained in roots after sequential extraction, and
bioaccumulation factors in shoots had the same values independently of Cd
concentration. At both Cd concentrations, the cadmium translocation index for F.
ovina was low (< 1), which is why this grass can be recommended for
phytostabilization of the metal under study.
PMID- 28517922
TI - Bariatric Surgery or Intensive Medical Therapy for Diabetes after 5 Years.
PMID- 28517923
TI - Prevalence of Parasitic Contaminationin Salad Vegetables Collected from
Supermarkets and Street Vendorsin Amman and Baqa'a - Jordan.
AB - One of the main ways in transmitting parasites to humans is through consuming
contaminated raw vegetables. The aim of this study was to evaluate the prevalence
of parasitological contamination (helminthes eggs, Giardia and Entamoeba
histolytica cysts) of salad vegetables sold at supermarkets and street vendors in
Amman and Baqa'a - Jordan. A total of 133 samples of salad vegetables were
collected and examined for the prevalence of parasites. It was found that 29% of
the samples were contaminated with different parasites. Of the 30 lettuce, 33
tomato, 42 parsley and 28 cucumber samples examined the prevalence of Ascaris
spp. eggs was 43%, 15%, 21% and 4%; Toxocara spp. eggs was 30%, 0%, 0% and 4%;
Giardia spp. cysts was 23%, 6%, 0% and 0%; Taenia/Echinococcus eggs was 20%, 0%,
5% and 0%; Fasciola hepatica eggs was 13%, 3%, 2% and 0%; and E. histolytica
cysts was 10%, 6%, 0% and 0%, respectively. There was no significant difference
in the prevalence of parasite in salad vegetables either between supermarkets and
street vendors, or between Amman and Baqa'a, Ascaris spp. was found to be the
highest prevalent parasite in salad vegetables from supermarkets and street
vendors and from Amman and Baqa'a. Our results pointed out that, the parasitic
contamination of salad vegetables found in our study might be caused by
irrigating crops with faecal contaminated water. We concluded that salad
vegetables sold in Amman and Baqa'a may cause a health risk to consumers.
PMID- 28517924
TI - Informed Consent.
PMID- 28517925
TI - Informed Consent.
PMID- 28517926
TI - Laser-Induced Population Inversion in Rhodamine 6G for Lysozyme Oligomer
Detection.
AB - Fluorescence spectroscopy is a common method for detecting amyloid fibrils in
which organic fluorophores are used as markers that exhibit an increase in
quantum yield upon binding. However, most of the dyes exhibit enhanced emission
only when bound to mature fibrils, and significantly weaker signals are obtained
in the presence of amyloid oligomers. In the concept of population inversion, a
laser is used as an excitation source to keep the major fraction of molecules in
the excited state to create the pathways for the occurrence of stimulated
emission. In the case of the proteins, the conformational changes lead to the
self-ordering and thus different light scattering conditions that can influence
the optical signatures of the generated light. Using this methodology, we show it
is possible to optically detect amyloid oligomers using commonly available
staining dyes in which population inversion can be induced. The results indicate
that rhodamine 6G molecules are complexed with oligomers, and using a laser
assisted methodology, weakly emissive states can be detected. Significant
spectral red-shifting of rhodamine 6G dispersed with amyloid oligomers and a
notable difference determined by comparison of spectra of the fibrils suggest the
existence of specific dye aggregates around the oligomer binding sites. This
approach can provide new insights into intermediate oligomer states that are
believed to be responsible for toxic seeding in neurodegeneration diseases.
PMID- 28517927
TI - Stable High-Performance Flexible Photodetector Based on Upconversion
Nanoparticles/Perovskite Microarrays Composite.
AB - Methylammonium lead halide perovskite has emerged as a new class of low
temperature-processed high-performance semiconductors for optoelectronics, but
with photoresponse limited to the UV-visible region and low environmental
stability. Herein, we report a flexible planar photodetector based on MAPbI3
microarrays integrated with NaYF4:Yb/Er upconversion nanoparticles (UCns) that
offers promise for future high performance and long-term environmental stability.
The promise derives from the confluence of several factors, including
significantly enhanced photons absorption in the visible spectrum, efficient
energy transition in the near-infrared (NIR) region, and inhibition of water
attack by the hydrophobic UCns capping layer. The UCns layer aided in remarkably
enhanced photodetection capability in the visible spectrum with detectivity (D*)
reaching 5.9 * 1012 Jones, among the highest reported values, due to the
increased photocarrier lifetime and decreased reflectivity. Excellent NIR
photoresponse with spectral responsivity (R) and D* as high as 0.27 A W-1 and
0.76 * 1012 Jones were obtained at 980 nm, respectively, superior to the reported
values of state-of-the-art organic-perovskite NIR photodetectors. Moreover, the
hydrophobic UCns capping layer serving as a moisture inhibitor allowed
significantly enhanced long-term environmental stability, e.g., 70% vs 27%
performance retained after 1000 h exposure in 30-40% RH humidity air without
encapsulation for the bilayer and the neat MAPbI3 devices, respectively. These
results suggest that the composite based on perovskite and UCns is promising for
constructing high-performance broadband optoelectronic devices with long-term
stability.
PMID- 28517928
TI - Integrated Modeling of Survival Data from Multiple Stressor Ecotoxicology
Experiments.
AB - Ecotoxicological assessments often focus on the response of an organism to an
individual contaminant under standardized laboratory conditions. Under more
ecologically realistic conditions, however, individuals are likely to be exposed
to a range of environmental conditions that have the potential to act as
additional stressors. Multiple-stressor experiments improve our understanding of
an organism's response to a toxicant under ecologically relevant conditions and
provide realistic risk assessment data. To date, there is no standardized method
for analyzing multiple-stressor data using dose-response regression. We present a
reliable technique to assess for the effects of additional stressors on an LCx
estimate in a consistent framework, providing interpretable results that
meaningfully deal with environmental changes and their possible impacts on
sensitivity estimates to a toxicant. The method is applicable to any data set
where toxicity tests are conducted at varying levels of one or more additional
stressors. We illustrate the method with data from an experiment that
investigates the effects of salinity and temperature on the sensitivity of the
subantarctic isopod Limnoria stephenseni to copper, where it is shown that the
major change in the LC50 can be primarily attributed to a specific temperature
increase. This method has been incorporated into an R package available at
github.com/ahproctor/LC50.
PMID- 28517929
TI - Computational Modeling and Simulation of CO2 Capture by Aqueous Amines.
AB - We review the literature on the use of computational methods to study the
reactions between carbon dioxide and aqueous organic amines used to capture CO2
prior to storage, reuse, or sequestration. The focus is largely on the use of
high level quantum chemical methods to study these reactions, although the review
also summarizes research employing hybrid quantum mechanics/molecular mechanics
methods and molecular dynamics. We critically review the effects of basis set
size, quantum chemical method, solvent models, and other factors on the accuracy
of calculations to provide guidance on the most appropriate methods, the expected
performance, method limitations, and future needs and trends. The review also
discusses experimental studies of amine-CO2 equilibria, kinetics, measurement and
prediction of amine pKa values, and degradation reactions of aqueous organic
amines. Computational simulations of carbon capture reaction mechanisms are also
comprehensively described, and the relative merits of the zwitterion,
termolecular, carbamic acid, and bicarbonate mechanisms are discussed in the
context of computational and experimental studies. Computational methods will
become an increasingly valuable and complementary adjunct to experiments for
understanding mechanisms of amine-CO2 reactions and in the design of more
efficient carbon capture agents with acceptable cost and toxicities.
PMID- 28517930
TI - Middle-Down 193-nm Ultraviolet Photodissociation for Unambiguous Antibody
Identification and its Implications for Immunoproteomic Analysis.
AB - Mass spectrometry (MS) has emerged as a powerful tool within the growing field of
immunoproteomics, which aims to understand antibody-mediated immunity at the
molecular-level based on the direct determination of serological antibody
repertoire. To date, these methods have relied on the use of high-resolution
bottom-up proteomic strategies that require effective sampling and
characterization of low abundance peptides derived from the antigen-binding
domains of polyclonal antibody mixtures. Herein, we describe a method that uses
restricted Lys-C enzymatic digestion to increase the average mass of proteolytic
IgG peptides (>=4.5 kDa) and produce peptides which uniquely derive from single
antibody species. This enhances the capacity to discriminate between very similar
antibodies present within polyclonal mixtures. Furthermore, our use of 193-nm
ultraviolet photodissociation (UVPD) improves spectral coverage of the antibody
sequence relative to conventional collision- and electron-based fragmentation
methods. We apply these methods to both a monoclonal and an antibody mixture. By
identifying from a database search of approximately 15 000 antibody sequences
those which compose the mixture, we demonstrate the analytical potential of
middle-down UVPD for MS-based serological repertoire analysis.
PMID- 28517931
TI - Correction to Synthesis, Antiviral Potency, in Vitro ADMET, and X-ray Structure
of Potent CD4 Mimics as Entry Inhibitors That Target the Phe43 Cavity of HIV-1
gp120.
PMID- 28517932
TI - Mechanism of Discrimination of 8-Oxoguanosine versus Guanosine by Escherichia
coli Fpg.
AB - The mutagenic 8-oxoguanosine monophosphate, the predominant product of DNA
oxidation, is excised by formamidopyrimidine glycosylase (Fpg) in bacteria. The
mechanism of recognition of 8-oxodG, which differs subtly from its normal
counterpart, guanosine monophosphate (dG), by Escherichia coli Fpg remains
elusive due to the lack of structural data of E. coli Fpg bound to 8-oxodG. Here,
we present solution-state structure of 8-oxodG oligomer bound to E. coli E3Q Fpg
using UV resonance Raman (UVRR) spectroscopy. The vibrational spectra report on
the pi-stacking and hydrogen bonding interactions established by 8-oxodG with E.
coli E3Q Fpg. Furthermore, we report on the interactions of E. coli E3Q Fpg with
the normal, undamaged nucleotide, dG. We show that E. coli Fpg recognizes 8-oxodG
and dG through their C2-amino group but only 8-oxodG forms extensive contacts
with E. coli Fpg. Our findings provide a basis for mechanism of lesion
recognition by E. coli Fpg.
PMID- 28517933
TI - Ag-Catalyzed Oxidative Cyclization Reaction of 1,6-Enynes and Sodium Sulfinate:
Access to Sulfonylated Benzofurans.
AB - A convenient protocol for the synthesis of sulfonylated benzofurans via Ag
catalyzed oxidative cyclization has been established. Chemically stable and
easily available sodium sulfinates were used as the sulfonylation reagents and
building block for the heterocycle construction. With this novel strategy,
various benzofurans bearing dual functional groups could be obtained in good
yields with high chemo- and regioselectivities under mild conditions.
PMID- 28517936
TI - In Situ Hydrogel Conditioning of Tissue Samples To Enhance the Drug's Sensitivity
in Ambient Mass Spectrometry Imaging.
AB - Ion suppression from the tissue matrix has a severe effect on the mass
spectrometry imaging (MSI) of drugs. This problem hinders further applications of
MSI in preclinical drug research and development. In this study, an in situ
hydrogel conditioning method was developed to enhance the sensitivity of air-flow
assisted desorption electrospray ionization (AFADESI)-MSI. Instead of the
traditional washing or digestion treatment in solvent, this method used a solid
phase hydrogel to "wash" tissue sections. It was demonstrated that this in situ
hydrogel conditioning method improved the drug signal by as much as 2- to 25-fold
in MSI, especially for hydrophobic compounds. Furthermore, the obvious
dislocation of analytes was not observed. The evaluation of spatial resolution
indicated that the amount of dislocation in tissue sections with the hydrogel
process was less than the resolution of AFADESI-MSI. The underlying reasons for
the MSI signal enhancement were initially investigated. The decreased signal
intensities of choline, betaine, and carnitine and the increased intensities of
the [M + H]+/[M + Na]+ and [M + H]+/[M + K]+ ratios for drugs in the mass spectra
of pretreated tissues provided evidence that this method can reduce the levels of
highly competitive quaternary ammonium and inorganic salts in the tissues. The
preformation of a thin liquid film for droplet pickup would also raise the
ionization efficiency of drugs. These results demonstrated that this in situ
hydrogel conditioning method provides a rapid and feasible approach to improving
the sensitivity of ambient MSI for drug mapping in tissues.
PMID- 28517935
TI - Regio- and Stereoselective Radical Perfluoroalkyltriflation of Alkynes Using
Phenyl(perfluoroalkyl)iodonium Triflates.
AB - A method for regio- and stereoselective anti-addition of the perfluoroalkyl and
the triflate group of phenyl(perfluoroalkyl)iodonium triflates to alkynes is
presented. The radical reaction uses cheap CuCl as a smart initiator and can be
conducted in gram scale. The perfluoroalkyltriflated products are readily further
functionalized, rendering this transformation valuable.
PMID- 28517934
TI - Plasma and Serum Metabolite Association Networks: Comparability within and
between Studies Using NMR and MS Profiling.
AB - Blood is one of the most used biofluids in metabolomics studies, and the serum
and plasma fractions are routinely used as a proxy for blood itself. Here we
investigated the association networks of an array of 29 metabolites identified
and quantified via NMR in the plasma and serum samples of two cohorts of ~1000
healthy blood donors each. A second study of 377 individuals was used to extract
plasma and serum samples from the same individual on which a set of 122
metabolites were detected and quantified using FIA-MS/MS. Four different
inference algorithms (ARANCE, CLR, CORR, and PCLRC) were used to obtain consensus
networks. The plasma and serum networks obtained from different studies showed
different topological properties with the serum network being more connected than
the plasma network. On a global level, metabolite association networks from
plasma and serum fractions obtained from the same blood sample of healthy people
show similar topologies, and at a local level, some differences arise like in the
case of amino acids.
PMID- 28517937
TI - Cellular Shuttles: Monocytes/Macrophages Exhibit Transendothelial Transport of
Nanoparticles under Physiological Flow.
AB - A major hurdle in the development of biomedical nanoparticles (NP) is
understanding how they interact with complex biological systems and navigate
biological barriers to arrive at pathological targets. It is becoming
increasingly evident that merely controlling particle physicochemical properties
may not be sufficient to mediate particle biodistribution in dynamic
environments. Thus, researchers are increasingly turning toward more complex but
likewise more physiological in vitro systems to study particle--cell/particle
system interactions. An emerging paradigm is to utilize naturally migratory cells
to act as so-called "Trojan horses" or cellular shuttles. We report here the use
of monocytes/macrophages to transport NP across a confluent endothelial cell
layer using a microfluidic in vitro model. With a custom-built flow chamber, we
showed that physiological shear stress, when compared to low flow or static
conditions, increased NP uptake by macrophages. We further provided a
mathematical explanation for the effect of flow on NP uptake, namely that the
physical exposure times of NP to cells is dictated by shear stress (i.e., flow
rate) and results in increased particle uptake under flow. This study was
extended to a multicellular, hydrodynamic in vitro model. Because monocytes are
cells that naturally translocate across biological barriers, we utilized a
monocyte/macrophage cell line as cellular NP transporters across an endothelial
layer. In this exploratory study, we showed that monocyte/macrophage cells adhere
to an endothelial layer and dynamically interact with the endothelial cells. The
monocytes/macrophages took up NP and diapedesed across the endothelial layer with
NP accumulating within the cellular uropod. These data illustrate that
monocytes/macrophages may therefore act as active shuttles to deliver particles
across endothelial barriers.
PMID- 28517939
TI - Breakdown of Optical Phonons' Splitting in Two-Dimensional Materials.
AB - We investigate the long-wavelength dispersion of longitudinal and transverse
optical phonon modes in polar two-dimensional materials, multilayers, and their
heterostructures. Using analytical models and density-functional perturbation
theory in a two-dimensional framework, we show that at variance with the three
dimensional case these modes are degenerate at the zone center but the
macroscopic electric field associated with the longitudinal-optical modes gives
rise to a finite slope at the zone center in their corresponding phonon
dispersions. This slope increases linearly with the number of layers and it is
determined solely by the Born effective charges of the material and the
dielectric properties of the surrounding media. Screening from the environment
can greatly reduce the slope splitting between the longitudinal and transverse
optical modes and can be seen in the experimentally relevant case of boron
nitride-graphene heterostructures. As the phonon momentum increases, the
intrinsic screening properties of the two-dimensional material dictate the
transition to a momentum-independent splitting similar to that of three
dimensional materials. These considerations are essential to understand
electrical transport and optical coupling in two-dimensional systems.
PMID- 28517938
TI - Glutamate Ligation in the Ni(II)- and Co(II)-Responsive Escherichia coli
Transcriptional Regulator, RcnR.
AB - Escherichia coli RcnR (resistance to cobalt and nickel regulator, EcRcnR) is a
metal-responsive repressor of the genes encoding the Ni(II) and Co(II) exporter
proteins RcnAB by binding to PRcnAB. The DNA binding affinity is weakened when
the cognate ions Ni(II) and Co(II) bind to EcRcnR in a six-coordinate site that
features a (N/O)5S ligand donor-atom set in distinct sites: while both metal ions
are bound by the N terminus, Cys35, and His64, Co(II) is additionally bound by
His3. On the other hand, the noncognate Zn(II) and Cu(I) ions feature a lower
coordination number, have a solvent-accessible binding site, and coordinate
protein ligands that do not include the N-terminal amine. A molecular model of
apo-EcRcnR suggested potential roles for Glu34 and Glu63 in binding Ni(II) and
Co(II) to EcRcnR. The roles of Glu34 and Glu63 in metal binding, metal
selectivity, and function were therefore investigated using a structure/function
approach. X-ray absorption spectroscopy was used to assess the structural changes
in the Ni(II), Co(II), and Zn(II) binding sites of Glu -> Ala and Glu -> Cys
variants at both positions. The effect of these structural alterations on the
regulation of PrcnA by EcRcnR in response to metal binding was explored using
LacZ reporter assays. These combined studies indicate that while Glu63 is a
ligand for both metal ions, Glu34 is a ligand for Co(II) but possibly not for
Ni(II). The Glu34 variants affect the structure of the cognate metal sites, but
they have no effect on the transcriptional response. In contrast, the Glu63
variants affect both the structure and transcriptional response, although they do
not completely abolish the function of EcRcnR. The structure of the Zn(II) site
is not significantly perturbed by any of the glutamic acid variations. The
spectroscopic and functional data obtained on the mutants were used to calculate
models of the metal-site structures of EcRcnR bound to Ni(II), Co(II), and
Zn(II). The results are interpreted in terms of a switch mechanism, in which a
subset of the metal-binding ligands is responsible for the allosteric response
required for DNA release.
PMID- 28517940
TI - Thermal Decomposition of Potential Ester Biofuels. Part I: Methyl Acetate and
Methyl Butanoate.
AB - Two methyl esters were examined as models for the pyrolysis of biofuels. Dilute
samples (0.06-0.13%) of methyl acetate (CH3COOCH3) and methyl butanoate
(CH3CH2CH2COOCH3) were entrained in (He, Ar) carrier gas and decomposed in a set
of flash-pyrolysis microreactors. The pyrolysis products resulting from the
methyl esters were detected and identified by vacuum ultraviolet photoionization
mass spectrometry. Complementary product identification was provided by matrix
infrared absorption spectroscopy. Pyrolysis pressures in the pulsed microreactor
were about 20 Torr and residence times through the reactors were roughly 25-150
MUs. Reactor temperatures of 300-1600 K were explored. Decomposition of CH3COOCH3
commences at 1000 K, and the initial products are (CH2?C?O and CH3OH). As the
microreactor is heated to 1300 K, a mixture of CH2?C?O and CH3OH, CH3, CH2?O, H,
CO, and CO2 appears. The thermal cracking of CH3CH2CH2COOCH3 begins at 800 K with
the formation of CH3CH2CH?C?O and CH3OH. By 1300 K, the pyrolysis of methyl
butanoate yields a complex mixture of CH3CH2CH?C?O, CH3OH, CH3, CH2?O, CO, CO2,
CH3CH?CH2, CH2CHCH2, CH2?C?CH2, HCCCH2, CH2?C?C?O, CH2?CH2, HC=CH, and CH2?C?O.
On the basis of the results from the thermal cracking of methyl acetate and
methyl butanoate, we predict several important decomposition channels for the
pyrolysis of fatty acid methyl esters, R-CH2-COOCH3. The lowest-energy
fragmentation will be a 4-center elimination of methanol to form the ketene
RCH?C?O. At higher temperatures, concerted fragmentation to radicals will ensue
to produce a mixture of species: (RCH2 + CO2 + CH3) and (RCH2 + CO + CH2?O + H).
Thermal cracking of the beta C-C bond of the methyl ester will generate the
radicals (R and H) as well as CH2?C?O + CH2?O. The thermochemistry of methyl
acetate and its fragmentation products were obtained via the Active
Thermochemical Tables (ATcT) approach, resulting in DeltafH298(CH3COOCH3) = -98.7
+/- 0.2 kcal mol-1, DeltafH298(CH3CO2) = -45.7 +/- 0.3 kcal mol-1, and
DeltafH298(COOCH3) = -38.3 +/- 0.4 kcal mol-1.
PMID- 28517941
TI - Cognitive and affective factors predicting daily somatic complaints in college
students.
AB - Evidence suggests that cumulative somatic complaints predict health care
utilization in college students. The symptom perception hypothesis and the
response expectancy theory are 2 theories concerning the generation of somatic
complaints. The symptom perception hypothesis suggests that negative affect
influences daily somatic complaints, whereas the response expectancy theory
surmises somatic complaint generation relates to response expectancies. Some
evidence suggests that understanding the complex interplay of these factors may
enhance prediction of daily somatic complaints. This study examines the combined
effects of state negative affect, trait negative affect, and response
expectancies in predicting daily somatic complaints. A total of 95 college
students took part in a 2-part study composed of 1 in-lab session followed by
completion of up to 7 daily diaries. Results show that state negative affect,
trait negative affect, and response expectancies all uniquely predict daily
somatic complaints. Our results support a cognitive-affective basis for somatic
complaints and suggest future research integrating biopsychosocial factors may be
useful in increasing our understanding. Furthermore, our results suggest
potential intervention targets when counseling college students experiencing
somatic complaints without physical origins. (PsycINFO Database Record
PMID- 28517943
TI - Implications of parent-child relationships for emerging adults' subjective
feelings about adulthood.
AB - Little is known about the role of parents in promoting their children's
successful transition to adulthood, particularly for college students who may
maintain stronger ties to parents than other emerging adults. The present study
therefore investigated longitudinal implications of parent-child relationship
qualities during emerging adults' first year of college for their feelings about
the upcoming transition to adulthood 3 years later, as well as implications of 3
types of parental control (behavioral control, psychological control, helicopter
parenting) for these associations. Multilevel models indicated that emerging
adults who reported less negativity in their relationships with mothers and
fathers felt more like adults 3 years later compared with emerging adults with
low-quality relationships, while high levels of psychological control and
helicopter parenting had detrimental implications for their vocational identity
development and perceived competence regarding their transition to adulthood.
However, nuanced interactions between parent-child relationship quality and
parental control indicated that behavioral control had positive implications for
outcomes if it occurred within the context of high-quality relationships, or when
utilized with sons. The present study highlights the complex role that parents
may play during college students' transition to adulthood, and future work should
continue to examine ways that clinicians can incorporate parents as a potential
resource for promoting emerging adults' successful transition to adulthood and
the workforce. (PsycINFO Database Record
PMID- 28517942
TI - Cognitive bias and paw preference in the domestic dog (Canis familiaris).
AB - Limb use, an indicator of hemispheric functioning, may be a useful predictor of
cognitive bias and hence vulnerability to welfare risk. The relationship between
cognitive bias and motor asymmetry, however, has been subject to little
investigation. This study explored the association between motor asymmetry and
cognitive bias in the domestic dog, a species that displays lateral bias in the
form of paw preferences and exhibits positive and negative affective states.
Thirty pet dogs had their paw preferences assessed using the Kong ball test. The
subjects' affective state was assessed using a cognitive bias test in which the
animals' latency to approach a bowl placed in 1 of 3 ambiguous positions was
recorded. Animals veering more toward a left-paw preference were found to be
significantly slower to approach the bowl placed in 1 of the ambiguous positions
than ambilateral or right-pawed dogs. Left-pawed subjects approached the bowl
located at the 3 ambiguous positions at roughly the same speed, while ambilateral
and right-pawed animals became increasingly slower to approach the bowl the
further it was located from the baited food bowl. The study points to a possible
relationship between cognitive bias and paw preference in the dog, with left
pawed animals being more negative or "pessimistic" in their cognitive outlook
than right-pawed or ambilateral individuals. It is proposed that limb preference
testing might offer a more practical and straightforward way of identifying
individuals at risk from poor welfare by virtue of how they perceive the world
than more time-consuming cognitive bias tests. (PsycINFO Database Record
PMID- 28517944
TI - Attitudes toward and prevalence of extramarital sex and descriptions of
extramarital partners in the 21st century.
AB - Using the most recent nine waves of data from the General Social Survey, which
consists of in-person interviews of independent probability samples of the adult
household population of the United States, the purposes of this study were to (a)
provide descriptive information on adults' attitudes toward extramarital sex,
lifetime and annual prevalence of extramarital sex among ever-married adults, and
the identity of the extramarital sex partner(s) of currently married adults; (b)
evaluate temporal trends in attitudes toward and prevalence of extramarital sex
from 2000 to 2016; and (c) test for gender differences in attitudes toward and
prevalence of extramarital sex and descriptions of the extramarital partner. The
percentages of Americans who reported that extramarital sex was always wrong
significantly declined from 2000 to 2016, whereas the percentage who reported it
was wrong only sometimes significantly increased. There was a statistically
significant linear decline in reported lifetime prevalence of extramarital sex
from 2000 (17.8%) to 2016 (16.3%), whereas there was no statistically significant
change in reported annual prevalence of extramarital sex (3.0%). People most
commonly reported having extramarital sex with a close personal friend (53.5%) or
neighbor, coworker, or long-term acquaintance (29.4%). Compared with women, men
were (a) less likely to report that extramarital sex was always wrong and more
likely to view it as almost always wrong, wrong only sometimes, or not wrong at
all; (b) more likely to report past-year and lifetime extramarital sex; and (c)
more likely to report extramarital sex with someone they knew casually. (PsycINFO
Database Record
PMID- 28517945
TI - Predicting growth in English and French vocabulary: The facilitating effects of
morphological and cognate awareness.
AB - The present study investigated the contribution of morphological and cognate
awareness to the development of English and French vocabulary knowledge among
young minority and majority language children who were enrolled in a French
immersion program. Participating children (n = 75) were assessed in English and
French on measures of morphological awareness, cognate awareness, and vocabulary
knowledge from Grades 1 to 3. Hierarchical linear modeling was used to
investigate linear trends in English and French vocabulary growth for minority
and majority language children and to identify metalinguistic contributions to
Grade 1 and Grade 3 English and French vocabulary performance and rate of growth.
Results demonstrated a similar pattern of prediction for both groups of children.
English and French morphological awareness and French-English cognate awareness
significantly predicted concurrent and longitudinal vocabulary development after
controlling for nonverbal reasoning, phonological awareness, and word
identification. The contributions of morphological awareness to English
vocabulary and cognate awareness to French vocabulary strengthened between Grades
1 and 2. These findings highlight the emerging importance of morphological and
cognate awareness in children's vocabulary development and suggest that these
metalinguistic factors can serve to broaden the vocabulary repertoire of children
who enter school with limited language proficiency. (PsycINFO Database Record
PMID- 28517946
TI - Why be moral? Moral identity motivation and age.
AB - Moral identity research to date has largely failed to provide evidence for
developmental trends in moral identity, presumably because of restrictions in the
age range of studies and the use of moral identity measures that are insensitive
to age-related change. The present study investigated moral identity motivation
across a broad age range (14-65 years, M = 33.48; N = 252) using a modified
version of the Good Self-Assessment Interview. Individuals' moral identity
motivation was coded and categorized as external, internal, or relationship
oriented. It was found that with age, external moral identity motivation
decreased, whereas internal moral identity motivation increased. Effects of age
were stronger in adolescence and emerging adulthood than in young adulthood and
middle age. Findings underscore the developmental nature of the moral identity
construct and suggest that moral motivation becomes more self-integrated with
age. (PsycINFO Database Record
PMID- 28517947
TI - Intolerance of uncertainty predicts increased striatal volume.
AB - Oversensitivity to uncertain future threat is usefully conceptualized as
intolerance of uncertainty (IU). Neuroimaging studies of IU to date have largely
focused on its relationship with brain function, but few studies have documented
the association between IU and the quantitative properties of brain structure.
Here, we examined potential gray and white-matter brain structural correlates of
IU from 61 healthy participants. Voxel-based morphometric analysis highlighted a
robust positive correlation between IU and striatal volume, particularly the
putamen. Conversely, tract-based spatial statistical analysis showed no evidence
for a relationship between IU and the structural integrity of white-matter fiber
tracts. Current results converge upon findings from individuals with anxiety
disorders such as obsessive-compulsive disorder (OCD) or generalized anxiety
disorder (GAD), where abnormally increased IU and striatal volume are
consistently reported. They also converge with neurobehavioral data implicating
the putamen in predictive coding. Most notably, the relationship between IU and
striatal volume is observed at a preclinical level, suggesting that the
volumetric properties of the striatum reflect the processing of uncertainty per
se as it relates to this dimensional personality characteristic. Such a
relationship could then potentially contribute to the onset of OCD or GAD, rather
than being unique to their pathophysiology. (PsycINFO Database Record
PMID- 28517948
TI - Randomized controlled trial of an internet cognitive behavioral skills-based
program for auditory hallucinations in persons with psychosis.
AB - OBJECTIVE: Despite strong evidence supporting the effectiveness of cognitive
behavioral therapy for psychosis (CBTp), most clinicians in the United States
have received little or no training in the approach and access remains very low,
indicating a potential role for technology in increasing access to this
intervention. Coping With Voices (CWV) is a 10-session, interactive, Web-based
CBTp skills program that was developed to meet this need, and was shown to be
feasible and associated with reduced severity of auditory hallucinations in a
previous pilot study. To more rigorously evaluate this program, a randomized
controlled trial was conducted comparing the efficacy of CWV to usual care (UC).
METHOD: The trial was conducted with a sample of 37 community mental health
center clients with schizophrenia and moderate-to-severe auditory hallucinations,
with assessments conducted at baseline, posttreatment, and 3-month follow-up.
RESULTS: Engagement in and satisfaction with the CWV program were high. Both the
CWV and UC groups improved comparably in severity of auditory hallucinations and
other symptoms over the treatment and at follow-up. However, participants in the
CWV program showed significantly greater increases in social functioning and in
knowledge about CBTp. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The results
suggest that the CWV program has promise for increasing access to CBTp, and
associated benefits in the management of distressing psychotic symptoms and
improving social functioning. (PsycINFO Database Record
PMID- 28517949
TI - Cognitive-behavioral treatments for criminogenic thinking: Barriers and
facilitators to implementation within the Veterans Health Administration.
AB - Cognitive-behavioral treatments for criminogenic thinking (i.e., antisocial
cognitions, attitudes, and traits) are regarded as best practices for reducing
criminal recidivism among justice-involved adults. However, the barriers and
facilitators to implementation of these treatments within large health care
systems such as the Veterans Health Administration (VHA) are largely unknown. To
address this gap, we conducted qualitative interviews with 22 Specialists from
the VHA's Veterans Justice Programs who had been trained in a cognitive
behavioral treatment for criminogenic thinking (i.e., Moral Reconation Therapy
[MRT], Thinking for a Change [T4C]). The time-intensiveness of these treatments
emerged as a barrier to implementation. Potential solutions identified were
patient incentives for treatment engagement, streamlining the curriculum, and
implementing the treatments within long-term/residential programs. At the program
level, providers' stigma/bias toward patients with antisocial tendencies was seen
as a barrier to implementation, as were time/resource constraints on providers.
To address the latter, use of peer providers to deliver the treatments and
partnerships between justice programs and behavioral health services were
suggested. At the system level, lack of recognition of criminogenic treatments as
evidence based, and uncertainty of sustained funds to support ongoing costs of
these treatments emerged as implementation barriers. To address the latter, a
train-the-trainers model was suggested. Our findings serve as a guide for
implementation of criminogenic treatments for providers and policymakers in VHA
and other large health care systems, which are increasingly called upon to
provide care to justice-involved adults in the community. (PsycINFO Database
Record
PMID- 28517950
TI - Gender differences in service utilization among Operations Enduring Freedom,
Iraqi Freedom, and New Dawn Veterans Affairs patients with severe mental illness
and substance use disorders.
AB - Severe mental illness (SMI) and substance use disorders (SUD) are among the more
chronic and costly mental health conditions treated in the Department of Veterans
Affairs (VA). Service use patterns of returning veterans with SMI and SUD have
received little attention. We examined gender differences in the utilization of
VA services among a national sample of Operations Enduring Freedom, Iraqi
Freedom, and New Dawn (OEF/OIF/OND) VA patients with SMI, SUD, and their
comorbidity (SMI/SUD) in their first year of established VA care (N = 24,166).
Outpatient services and acute-residential stays were modeled using negative
binomial and logistic regression, respectively. Among all diagnostic categories,
men used outpatient services less often than did women, including primary care
(adjusted rate ratio [ARR] = .71, 95% confidence interval CI [.68, .74]), mental
health (ARR = .85, 95% CI [.80, .91]), and addiction (ARR = .91, 95% CI [.83,
.99]) services. For emergency department (ED) and psychiatric inpatient services,
gender interacted significantly with diagnosis. The combination of SMI/SUD
compared to either SMI or SUD conferred greater risk of ED utilization among men
than women (adjusted odds ratio [AOR] = 2.09, 95% CI [1.24, 3.51], and 1.95, 95%
CI [1.17, 3.26], respectively). SMI versus SUD conferred greater risk of
psychiatric inpatient utilization among men than women (AOR = 1.83, 95% CI [1.43,
2.34]). Our findings point to gender differences in outpatient and acute service
utilization among OEF/OIF/OND VA patients with some of the more chronic and
costly mental health conditions. Further investigation of health care utilization
patterns is needed to understand factors driving these gender differences to
ensure that veterans have appropriate access to the services they need. (PsycINFO
Database Record
PMID- 28517951
TI - Treatment-as-usual therapy targets for comorbid youth disproportionately focus on
externalizing problems.
AB - This study examined whether psychological treatment for youth with comorbid
externalizing and internalizing disorders targets externalizing rather than
internalizing pathology. Therapist-reported treatment targets for youth (N = 679)
with (a) only internalizing diagnoses (n = 195); (b) only externalizing diagnoses
(n = 314); (c) a primary internalizing diagnosis and at least 1 additional
externalizing diagnosis (n = 75); and (d) a primary externalizing diagnosis and
at least 1 additional internalizing diagnosis (n = 95) receiving treatment-as
usual in a public mental health system of care were examined. Treatment targets
that appeared significantly more often in the externalizing-only and
internalizing-only diagnostic groups were empirically determined, and a derived
proportional measure of these targets was analyzed across all 4 diagnostic
groups, controlling for effects of additional client and treatment
characteristics. As required by the target selection method, the proportion of
externalizing targets selected in treatment was greatest for youth with
externalizing-only diagnoses and least for youth with internalizing-only
diagnoses. Importantly, the co-occurrence of a secondary externalizing disorder
with a primary internalizing disorder resulted in a large increase in the
proportion of externalizing targets endorsed, whereas the co-occurrence of an
internalizing disorder with a primary externalizing disorder resulted in a
comparatively small decrease in the proportion of externalizing targets endorsed.
Results persisted despite several covariates also predicting increased focus on
externalizing targets, including male gender and younger age. These findings
suggest that community therapists tend to prioritize externalizing over
internalizing problems during treatment for such comorbid youth. Implications for
practice, research and dissemination/implementation efforts are discussed.
(PsycINFO Database Record
PMID- 28517953
TI - ?
PMID- 28517952
TI - DNA methylation and transcription onset in the brain.
AB - AIM: The goal of this study was to test the state of methylation of transcription
start positions in DNA that are actively involved in transcription. MATERIALS &
METHODS: We used sequential ChIP-bisulfite-sequencing with an antibody to RNpolII
PS5 to map the state of methylation of actively transcribing transcription start
sites (TSS). RESULTS: TSS that RNApolII-PS5 physically bind to, are ubiquitously
unmethylated. TSS that appear to be both heavily methylated and transcriptionally
active are truly a mixture of unmethylated TSS with bound RNApolII-PS5 in some
nuclei and unbound methylated TSS in other nuclei. CONCLUSION: TSS DNA
methylation is universally inconsistent with transcription onset and could
therefore serve as a digital count of the fraction of nuclei with methylation
silenced TSS.
PMID- 28517954
TI - On the Rocks: Microbiological Quality and Microbial Diversity of Packaged Ice in
Southern California.
AB - Ice is defined as a food and is frequently used in direct contact with food and
beverages. Packaged ice is commercially produced and can be easily found in
grocery and convenience stores. However, the quality and safety of packaged ice
products is not consistent. The Packaged Ice Quality Control Standards manual
(PIQCS) published by the International Packaged Ice Association provides the
quality and processing standards for packaged ice produced by its members.
Packaged ice produced on the premise of stores (on-site packaged ice) is not
required to be in compliance with these standards. In this study, packaged ice
produced by manufacturing plants or by in-store bagger (ISB) machines and on-site
packaged ice were compared for their microbiological quality and microbial
diversity. Our results revealed that 19% of the 120 on-site packaged ice samples
did not meet the PIQCS microbial limit of 500 CFU/mL (or g) and also the absence
of coliforms and Escherichia coli . Staphylococci were found in 34% of the on
site packaged ice samples, most likely through contamination from the packaging
workers. None of the ISB and manufactured packaged ice samples had unacceptable
microbial levels, and all were devoid of staphylococci. Salmonella was absent in
all samples analyzed in this study. Microbial community analysis of ice based on
16S/18S rRNA targeted sequencing revealed a much higher microbial diversity and
abundance in the on-site packaged ice than in the ISB ice. Proteobacteria,
especially Alphaproteobacteria and Betaproteobacteria, were the dominant
bacterial groups in all samples tested. Most of these bacteria were oligotrophic;
however, a few opportunistic or potential pathogens were found at low levels in
the on-site packaged ice but not in the ISB packaged ice. The types of microbes
identified may provide information needed to investigate potential sources of
contamination. Our data also suggest a need for enforcement of processing
standards during the on-site packaging of ice.
PMID- 28517955
TI - The long-term risk of smoking in diabetic patients with stable ischemic heart
disease treated with intensive medical therapy and lifestyle modification.
AB - Introduction The long-term risk of smoking in diabetic patients with stable
ischemic heart disease (SIHD) is unknown. We sought to analyze the impact of
smoking on outcomes of diabetic patients with SIHD when other cardiovascular risk
factors are being aggressively treated. Methods The Bypass Angioplasty
Revascularization Investigation 2 Diabetes (BARI 2D) trial randomized 2368
diabetics with SIHD to intensive medical therapy (IMT) with prompt
revascularization or IMT alone. Smoking status was obtained at baseline, 6
months, and 1, 2, 3, 4 and 5 years. The primary endpoint of interest was all
cause mortality. Results Of 2360 patients, 33.1% of patients never smoked, 54.4%
were former smokers, and 12.5% were current smokers. The rate of all-cause
mortality was greater for current (2.5 deaths/100 patient-years) and former
smokers (3.1 deaths/100 patient-years) than never smokers (2.1 deaths/100 patient
years) (P = 0.007). Cardiac death, cardiovascular death, fatal or nonfatal
myocardial infarction, and fatal or nonfatal stroke were not increased in current
or former smokers compared with never smokers. Compared with never smokers,
current smokers experienced a 49% increased hazard of death (Hazard Ratio (HR)
1.49, 95% Confidence Interval (CI): 0.97-2.29, P = 0.07) whereas former smokers
had a 37% increased hazard of death (HR 1.37, 95% CI: 1.04-2.79, P = 0.02) when
considering smoking status as a time-dependent variable and adjusting for factors
that differed by smoking status. Conclusions Current and former smoking are
associated with increased all-cause mortality in diabetics with SIHD but not with
increased cardiovascular morbidity or mortality.
PMID- 28517956
TI - The longitudinal association between anxiety and Internet addiction in
adolescence: The moderating effect of classroom extraversion.
AB - Background and aims The risk effect of anxiety on addictive behaviors, including
Internet addiction (IA), has repeatedly been highlighted in the international
literature. However, there is a lack of longitudinal studies examining this
association in relation to proximal context effects, particularly in adolescence.
Such findings would shed light on potential age- and proximal context-related
variations in the anxiety-IA association that could better inform IA prevention
and intervention initiatives. Methods In this study, 648 adolescents, embedded in
34 classrooms, were assessed at the age of 16 and again at the age of 18 to
examine the effect of anxiety on IA behaviors in relation to the average level of
classroom extraversion. IA was assessed with the Internet Addiction Test (Young,
1998), anxiety with the relevant subscale of the Symptom Checklist 90 - Revised
(Derogatis & Savitz, 1999) and classroom extraversion with the synonymous
subscale of the Five Factor Questionnaire (Asendorpf & van Aken, 2003). A three
level hierarchical linear model was calculated. Results The present findings
demonstrated that: (a) higher levels of anxiety were significantly associated
with higher IA behaviors, (b) the strength of this association did not vary over
time (between 16 and 18 years old), and (c) however, it tended to weaken within
classrooms higher in extraversion. Discussion This study indicated that the
contribution of individual IA risk factors might differently unfold within
different contexts.
PMID- 28517957
TI - Novel drug and soluble target tolerant antidrug antibody assay for therapeutic
antibodies bearing the P329G mutation.
AB - AIM: Bridging immunoassays for detection of antidrug antibodies (ADAs) are
typically susceptible to high concentrations of residual drug. Sensitive drug
tolerant assays are, therefore, needed. MATERIALS & METHODS: An immune complex
assay to detect ADAs against therapeutic antibodies bearing Pro329Gly mutation
was established. The assay uses antibodies specific for the Pro329Gly mutation
for capture and human soluble Fcgamma receptor for detection. RESULTS: When
compared with a bridging assay, the new assay showed similar precision, high
sensitivity to IgG1 ADA and dramatically improved drug tolerance. However, it was
not able to detect early (IgM-based) immune responses. CONCLUSION: Applied in
combination with a bridging assay, the novel assay serves as orthogonal assay for
immunogenicity assessment and allows further characterization of ADA responses.
PMID- 28517958
TI - Distance of translation as a predictor of failure of fixation in paediatric
supracondylar fractures.
AB - Introduction This study investigates the influence of incomplete reduction of
supracondylar fractures on the incidence of loss of reduction requiring
reoperation Materials and methods A review of 107 consecutive patients presenting
with supracondylar fractures treated with closed reduction and Kirschner wire
stabilisation, between January 2011 and March 2013, was conducted. The mean age
was 5 years (range 10 months to 12 years). Pre-, intra- and postoperative
radiographs were reviewed. All patients who had failure of fixation requiring
revision surgery were identified. Results Ninety-nine patients had an initial
adequate radiographic reduction. Of these, one (1%) required revision surgery.
Eight patients had an initial incomplete radiographic reduction and, of these,
six (75%) required revision surgery (P < 0.0001). Discussion Supracondylar
fractures treated with closed reduction and K wire stabilisation require adequate
intraoperative reduction. Incomplete reduction should not be accepted, as despite
the bones potential to remodel, the risk of further loss of reduction is high,
requiring reoperation.
PMID- 28517960
TI - A Rapid Seedling Resistance Assay Identifies Wild Tomato Lines That Are Resistant
to Pseudomonas syringae pv. tomato Race 1.
AB - Bacterial speck caused by Pseudomonas syringae has historically been controlled
by the Pto/Prf gene cluster. Emerging strains like P. syringae pv. tomato race 1
overcome resistance conferred by Pto/Prf, and can cause serious crop loss under
appropriate environmental conditions. We developed a rapid assay to screen wild
tomato seedlings for resistance to P. syringae pv. tomato race 1. We established
the seedling resistance assay using the well-characterized P. syringae pv. tomato
race 0 strain, DC3000, which is recognized in tomato cultivars carrying Pto/Prf
(PtoR) and causes disease in isogenic lines lacking this cluster (PtoS). We
optimized infectious conditions for P. syringae on tomato seedlings and
demonstrated that tomato seedlings respond like adult tomato plants in critical
measures of susceptibility and immunity, including the hypersensitive response,
rapid ion leakage, restricted bacterial proliferation, and phenotypic resistance.
After establishing infectious conditions for P. syringae pv. tomato race 1 on
tomato seedlings, we screened 96 wild accessions and identified two accessions
with strong P. syringae pv. tomato race 1 resistance, Solanum neorickii LA1329
and S. habrochaites LA1253, which are also resistant to bacterial infection as
adult plants. This rapid high throughput seedling assay has many advantages,
including reduced plant growth time and large sample sizes, and will allow for
large-scale screening of resistance in tomato.
PMID- 28517959
TI - POMICS: A Simulation Disease Model for Timing Fungicide Applications in
Management of Powdery Mildew of Cucurbits.
AB - A weather-based simulation model, called Powdery Mildew of Cucurbits Simulation
(POMICS), was constructed to predict fungicide application scheduling to manage
powdery mildew of cucurbits. The model was developed on the principle that
conditions favorable for Podosphaera xanthii, a causal pathogen of this crop
disease, generate a number of infection cycles in a single growing season. The
model consists of two components that (i) simulate the disease progression of P.
xanthii in secondary infection cycles under natural conditions and (ii) predict
the disease severity with application of fungicides at any recurrent disease
cycles. The underlying environmental factors associated with P. xanthii infection
were quantified from laboratory and field studies, and also gathered from
literature. The performance of the POMICS model when validated with two datasets
of uncontrolled natural infection was good (the mean difference between simulated
and observed disease severity on a scale of 0 to 5 was 0.02 and 0.05). In
simulations, POMICS was able to predict high- and low-risk disease alerts.
Furthermore, the predicted disease severity was responsive to the number of
fungicide applications. Such responsiveness indicates that the model has the
potential to be used as a tool to guide the scheduling of judicious fungicide
applications.
PMID- 28517961
TI - Overcoming chemoresistance in cancer stem cells with the help of microRNAs in
colorectal cancer.
AB - It has been recognized that acute resistance to chemotherapy mediated by post
transcriptional and translational control is crucial to influence response and
survival in cancer treatment. Tumor cells are highly heterogeneous and have the
ability to adapt a resistance phenotype through epigenetic regulations such as
microRNAs. This poses a major challenge to the treatment of advanced stage colon
cancer patients. Colon cancer stem cells have been identified as one of the major
contributors to resistance of colon cancer to chemotherapy. Through various
mechanisms, these cells are able to resist the effects of traditional
chemotherapeutics. The challenge posed by these cells is further enhanced by
their plastic nature, where cells can transition between non-stem cancer cells
and cancer stem cells creating a moving target. In this editorial, we discuss
some of the recent advancements in overcoming chemoresistance associated with
colon cancer stem cells with the help of microRNAs.
PMID- 28517963
TI - Novel strategies in vaccine design: can nanocapsules help prevent and treat
hepatitis B?
PMID- 28517962
TI - Inhibition of the Continuum of Radiation-Induced Normal Tissue Injury by a Redox
Active Mn Porphyrin.
AB - Normal tissue damage after head and neck radiotherapy involves a continuum of
pathologic events to the mucosa, tongue and salivary glands. We examined the
radioprotective effects of MnBuOE, a redox-active manganese porphyrin, at three
stages of normal tissue damage: immediate (leukocyte endothelial cell [L/E]
interactions), early (mucositis) and late (xerostomia and fibrosis) after
treatment. In this study, mice received 0 or 9 Gy irradiation to the oral cavity
and salivary glands +/- MnBuOE treatment. Changes in leukocyte-endothelial cell
interactions were measured 24 h postirradiation. At 11 days postirradiation,
mucositis was assessed with a cathepsin-sensitive near-infrared optical probe.
Stimulated saliva production was quantified at 11 weeks postirradiation. Finally,
histological analyses were conducted to assess the extent of long-term effects in
salivary glands at 12 weeks postirradiation. MnBuOE reduced oral mucositis,
xerostomia and salivary gland fibrosis after irradiation. Additionally, although
we have previously shown that MnBuOE does not interfere with tumor control at
high doses when administered with radiation alone, most head and neck cancer
patients will be treated with the combinations of radiotherapy and cisplatin.
Therefore, we also evaluated whether MnBuOE would protect tumors against
radiation and cisplatin using tumor growth delay as an endpoint. Using a range of
radiation doses, we saw no evidence that MnBuOE protected tumors from radiation
and cisplatin. We conclude that MnBuOE radioprotects normal tissue at both early
and late time points, without compromising anti-tumor effects of radiation and
cisplatin.
PMID- 28517964
TI - Introductory paragraph.
PMID- 28517965
TI - BSRM Annual Meeting London - 2015 - Poster & Free Paper Abstracts: Free Paper
(Podium presentations).
PMID- 28517966
TI - Abstracts of meeting DCRM November 2016.
AB - The Netherlands Society of Rehabilitation Medicine (NSRM) represents about 850
members. Scientific meetings are held twice a year. On 9 and 10 November 2017,
the NSRM will organise the Dutch Congress of Rehabilitation Medicine (DCRM) in
cooperation with the Baltic North Sea Forum on Physical and Rehabilitation
Medicine (BNF-PRM) and the Royal Belgian Society of Physical and Rehabilitation
Medicine (RBSPRM) in Maastricht, The Netherlands. The theme of this highly
interactive and interdisciplinary conference is 'Moving ahead towards
participation'. Abstracts for oral and poster presentations are peer reviewed
before selection. These ten abstracts were presented and selected for publication
during DCRM 2016 in The Netherlands. Selection was done by the jury, consisting
of members of the scientific committee of the NSRM. Contact person within the
NSRM: AH Vrieling, University Medical Center Groningen, PO Box 30002, 9715 RA,
Haren, The Netherlands. Email: a.h.vrieling@umcg.nl.
PMID- 28517968
TI - A community-based qualitative study of intergenerational resilience with
Palestinian refugee families facing structural violence and historical trauma.
AB - The purpose of this study was to explore resilience processes in Palestinian
refugee families living under Israeli occupation for multiple generations.
Qualitative methods, critical postcolonial theories, and community-based research
approaches were used to examine intergenerational protective practices and to
contribute to reconceptualizations of resilience from indigenous perspectives.
First, the researcher developed a collaborative partnership with a
nongovernmental organization (NGO) in a UN refugee camp in the occupied West
Bank. Then, with the support of this NGO, semistructured group and individual
interviews were completed with a total of 30 participants ( N = 30) ranging in
age from 18 to 90 years old coming from 5 distinct extended family networks.
Using grounded theory situational analysis, the findings were organized in a
representation entitled Palestinian Refugee Family Trees of Resilience (PRFTR).
These findings explain resilience in terms of three interrelated themes: (a)
Muqawama/resistance to military siege and occupation; (b) Awda/return to cultural
roots despite historical and ongoing settler colonialism; and (c)
Sumoud/perseverance through daily adversities and accumulation of trauma. The
study findings shed light on how Palestinian families cultivate positive
adaptation across generations and highlight how incorporating community-based
perspectives on the historical trauma and violent social conditions of everyday
life under occupation may be critical for promoting resilience. Results may be
relevant to understanding the transgenerational transmission of trauma and
resilience within other displaced communities internationally.
PMID- 28517967
TI - Cruel to Be Kind: Factors Underlying Altruistic Efforts to Worsen Another
Person's Mood.
AB - When aiming to improve another person's long-term well-being, people may choose
to induce a negative emotion in that person in the short term. We labeled this
form of agent-target interpersonal emotion regulation altruistic affect worsening
and hypothesized that it may happen when three conditions are met: (a) The agent
experiences empathic concern for the target of the affect-worsening process, (b)
the negative emotion to be induced helps the target achieve a goal (e.g., anger
for confrontation or fear for avoidance), and (c) there is no benefit for the
agent. This hypothesis was tested by manipulating perspective-taking instructions
and the goal to be achieved while participants ( N = 140) played a computer-based
video game. Participants following other-oriented perspective-taking
instructions, compared with those following objective perspective-taking
instructions, decided to induce more anger in a supposed fellow participant who
was working to achieve a confrontation goal and to induce more fear in a supposed
fellow participant who was working to achieve an avoidance goal.
PMID- 28517969
TI - Prevalence and determinants of depression among patients under the care of
traditional health practitioners in a Kenyan setting: Policy implications.
AB - In Kenya, there is paucity of information on depression among traditional health
practitioner (THP) patients, particularly in rural areas. The aim of this study
was to estimate prevalence and identify determinants of major depressive disorder
(MDD) among patients of THP in rural Kenya using the World Health Organization
(WHO) Mental Health Gap Action Programme Intervention Guideline (mhGAP-IG). All
adult patients seeking care from trained THPs (either traditional healers such as
diviners and herbalists or faith healers, who use treatments such as prayers,
laying hands on patients, or providing holy water and ash to their patients) over
a period of 3 months (September 2014 to November 2014) were screened for
depression using mhGAP-IG and their sociodemographic characteristics recorded.
Overall, the prevalence of depression among THP patients was 22.9%. Being older,
female, single, divorced or separated, as well as unemployment and lack of
education were found to be significant determinants of depression. Patients with
MDD frequently presented with suicidal behavior (32.9%, OR = 5.94, p < .0001)
compared to those that had at least one psychotic symptom (26.3%, OR = 3.65, p <
.0001). A measure of the accuracy of THPs' assessment of MDD showed 86%
specificity and 46% sensitivity and the area under receiver operating
characteristics (ROC) curve was 0.686. Our findings shed light on the prevalence
of depression among THP patients and thus highlight the need for further research
on diagnostic tools for use among THPs in order to avoid substandard care and
promote reliance on more evidence-based methods of care.
PMID- 28517971
TI - Soft Tissue Changes Around Immediately Placed Implants: A Systematic Review and
Meta-Analyses With at Least 12 Months of Follow-Up After Functional Loading.
AB - BACKGROUND: Immediate implant placement (IIP) is predictable but can lead to
esthetic challenges, including midfacial recession (MFR) and papillary height
(PH) loss. The aim of this systematic review is to examine the effect of IIP on
MFR and PH after at least 12 months of functional loading. METHODS: Literature
review of the Cochrane and MEDLINE electronic databases and hand search up to
January 2016 identified eligible studies. Four reviewers independently assessed
data quality and methodology. RESULTS: A total of 106 articles satisfied the
inclusion criteria. Twelve studies qualified for three meta-analyses. MFR was
slightly less in conventional implant placement (CIP) than in IIP, but the result
was not statistically significant (mean difference [MD] -0.064 mm; P = 0.687).
Similarly, there was better PH maintenance in CIPs, with statistical significance
for distal PH (DPH) only (cumulative PH: MD -0.396, P = 0.010; DPH: MD -0.765, P
<0.001; mesial PH [MPH]: MD -0.285, P = 0.256). MFR was slightly less in IIP with
thick versus thin biotypes, but not statistically significantly different (MD
0.373, P = 0.243). Pooled data showed statistically significantly less MFR and
better PH maintenance in IIP with thick biotype (MFR: MD -0.478, P <0.001;
cumulative PH: MD -0.287, P <0.001; MPH: MD -0.288, P <0.001; DPH: MD -0.310, P
<0.001). Non-significantly less MFR (MD 0.253, P = 0.384) and significantly
better PH maintenance were found in IIP with immediate provisionalization versus
conventional restoration (MD -0.519, P = 0.028). CONCLUSIONS: IIP in thick
biotype and with immediate provisionalization had less MFR and better PH than IIP
in thin biotype or with delayed restoration. However, these findings should be
interpreted with caution due to high heterogeneity, which was calculated using
comprehensive meta-analysis statistical software that took into account sample
size and different treatment groups, and limited qualified studies.
PMID- 28517970
TI - Osteoblast Progenitors Enhance Osteogenic Differentiation of Periodontal Ligament
Stem Cells.
AB - BACKGROUND: Osteoblasts and periodontal ligament stem cells (PDLSCs) play an
important role in maintaining physiologic function of periodontal tissues and
participating in periodontal regeneration. Elucidation of interactions between
osteoblasts and PDLSCs will aid understanding of periodontal regeneration
mechanisms. This study aims to determine whether preosteoblasts can promote
osteoblastic/cementoblastic differentiation of PDLSCs. METHODS: PDLSCs were
cultured alone (control group), or cocultured indirectly with human gingival
fibroblasts (HGFs) (HGFs group) or MC3T3-E1 cells (OB groups). Alkaline
phosphatase (ALP) activity and gene/protein expressions levels of ALP, runt
related transcription factor-2, and osteopontin (OPN) were assessed. Cementum
attachment protein and cementum protein 23 messenger RNA expressions were also
evaluated. Bone morphogenetic protein (BMP)-2 secreted by HGFs/MC3T3-E1 cells was
assessed by enzyme-linked immunosorbent assay. Extracellular matrix calcification
was measured by staining to quantify calcium content. RESULTS: ALP activity and
gene/protein expression levels of osteogenic markers were significantly higher in
the OB groups compared with the HGFs and control groups. Optimal enhancement of
these parameters occurred at cell ratios of 2:1 to 1:1 (MC3T3-E1:PDLSCs).
Mineralized nodule formation and calcium content were significantly increased in
the OB groups compared with the HGF and control groups. The greatest improvement
took place at the 2:1 (MC3T3-E1:PDLSCs) seeding ratio. BMP-2 from MC3T3-E1
conditioned medium was significantly and time-dependently increased compared with
that from HGF-conditioned medium. CONCLUSION: Preosteoblasts can indirectly
enhance the osteoblastic/cementoblastic differentiation and mineralization of
PDLSCs with an optimal preosteoblasts:PDLSCs ratio in the range of 2:1 to 1:1.
PMID- 28517972
TI - Glycated Collagen Stimulates Differentiation of Gingival Myofibroblasts.
AB - BACKGROUND: Glucose-derived metabolites may alter the structure and biologic
properties of important proteins in periodontium, such as collagens. As a
consequence, it is possible that collagen-binding cells may change their
phenotypic traits. Although the glucose-derived product methylglyoxal (MGO) has
been detected in periodontal lesions, the precise effect of collagen glycation on
gingival connective tissue biology is not fully understood. The present study
evaluates whether collagen glycation by MGO may affect phenotypic properties and
remodeling capacity of human gingival fibroblasts (HGFs). METHODS: Primary
cultures of HGFs were grown on Type I collagen matrices previously treated with
MGO. Cell cultures were tested for cell viability, apoptosis, alpha-smooth muscle
actin (SMA), fibronectin (FN) production, and collagen remodeling. Mechanical
properties and morphology of MGO-treated collagen gels were evaluated using
rheometry and atomic force microscopy. Statistical analysis was performed by
Kruskal-Wallis and Mann-Whitney U tests. RESULTS: MGO-treated collagen did not
affect cell viability or apoptosis. In addition, MGO did not induce significant
changes in morphology or mechanical properties of the collagen matrix. However,
MGO-treated collagen stimulated an increase in the myofibroblast marker alpha
SMA, production and assembly of FN, and contraction of collagen matrices.
Moreover, use of a triple-helical peptide that reconstitutes the collagen-binding
domain for integrins GFOGER reverted the assembly of FN induced by MGO-treated
collagen. CONCLUSIONS: The present study shows that collagen glycation by MGO
stimulates differentiation of myofibroblasts and production and assembly of FN.
These responses may alter the homeostatic balance and wound-healing response of
gingival connective tissues affected by diabetes mellitus or aging.
PMID- 28517973
TI - Periodontal Referral Patterns in Australia: 2000 Versus 2015.
AB - BACKGROUND: A previous study investigated differences in the severity of
periodontal disease on referral for specialist care between 1980 and 2000 across
the United States. The present study finds patients referred in 2000 had greater
severity of periodontal disease than those referred 20 years ago. METHODS: A
retrospective analysis of 384 charts was completed from three periodontal
practices across the east coast of Australia. Two time periods were investigated:
2000 to 2001 and 2015 to 2016. From these charts, the following data were
recorded: 1) age; 2) sex; 3) smoking status; 4) number of missing teeth; and 5)
number of teeth planned for extraction as part of a treatment plan at initial
examination. Additionally, degree of periodontal severity was determined and
recorded. The classification system was based on that used by the previous study,
wherein case Types I to IV defined increasing severity of periodontal disease,
and Type V defined referrals for needs other than periodontal disease (e.g.,
crown lengthening and implants). RESULTS: Overall, patients seen in 2015
presented with a greater percentage of Type IV and Type V cases. Smoking
prevalence reduced significantly across the three locations between the two time
periods. No consistent or noteworthy trends were identified with regard to number
of missing teeth or number of teeth planned for extraction. CONCLUSIONS:
Consistent with the results of a similar previous study, there appears to be a
trend for more severe periodontal conditions being referred to periodontists.
This is concerning given that more severe periodontal conditions tend to be more
difficult to manage conservatively and reliably.
PMID- 28517974
TI - Impact of Docosahexaenoic Acid Therapy on Subgingival Plaque Microbiota.
AB - BACKGROUND: Oral docosahexaenoic acid (DHA) + aspirin therapy has been shown to
reduce periodontal probing depth (PD) and local inflammatory mediators in
gingival crevicular fluid (GCF) among patients with untreated chronic periodontal
disease. Whether DHA + aspirin therapy influences specific bacterial burden in
this setting is unknown. Thus, the aim of this study is to evaluate the impact of
DHA with low-dose aspirin therapy on periodontal bacterial profile in patients
with periodontitis. METHODS: Fifty-five adults with moderate-to-severe
periodontitis were enrolled in a randomized, 3-month double-masked, placebo
controlled trial of daily 2 g DHA or placebo capsules enriched with 81 mg
aspirin; 46 enrollees completed the trial. In addition to clinical measurements
and GCF sampling, subgingival plaque samples were collected from four posterior
sites in all participants and analyzed by the checkerboard DNA-DNA hybridization
technique. Presence of 40 periodontal bacterial species at baseline and 3 months
was semiquantitatively estimated. RESULTS: Despite broad improvements in clinical
parameters, total bacteria and individual species counts in dental plaque did not
differ significantly between baseline and 3 months in either group (P >0.1 for
all). A modest effect of DHA + aspirin on Porphyromonas gingivalis counts was
associated with 14% (95% confidence interval: 3% to 35%) of the observed benefit
of DHA on PD. DHA + aspirin had no significant effect on individual plaque
bacterial counts in unadjusted models or those adjusted for age, sex, and race (P
>0.1 for all). CONCLUSIONS: This pilot randomized, controlled trial suggests that
DHA + aspirin therapy improves periodontitis largely by modulating host
inflammatory response. Changes in individual species levels in subgingival plaque
microbiota were not detectable; however, a small portion of the benefit appears
to stem from changes in P. gingivalis levels in the DHA + aspirin treatment
group. Whether this change in P. gingivalis levels leads to biofilm alteration
with reversal of dysbiosis requires further longitudinal and more specific
investigations.
PMID- 28517975
TI - Relationship Between Periodontal Screening and Recording Index Scores and Need
for Periodontal Access Surgery.
AB - BACKGROUND: The validity of using pretreatment Periodontal Screening and
Recording (PSR) index sextant scores to estimate periodontal access surgery needs
is evaluated in patients with chronic periodontitis before and after completion
of non-surgical periodontal therapy. METHODS: In 110 adults, pretreatment probing
data identified 486 sextants with PSR scores of 4 and 125 sextants with PSR
scores of 3. Periodontal access surgery needs for all sextants were determined
prior to treatment and after completion of non-surgical periodontal therapy for
213 sextants in 38 patients by two experienced periodontist examiners. RESULTS:
PSR scores of 4 identified untreated sextants with periodontal access surgery
needs significantly better than PSR scores of 3 (odds ratio = 27.8; P <0.001) in
multilevel, mixed-effects, logistic regression modeling analysis. However, only
37.6% of sextants with both pretreatment PSR scores of 4 and a pretreatment
periodontal access surgery need continued to have surgical access needs after
completion of non-surgical periodontal therapy. A higher percentage of sextants
with PSR scores of 4 or 3 revealed periodontal access surgical needs when Class
II or III furcation involvements and/or Grade II or III tooth mobility were also
detected in the sextant than when these parameters were not detected.
CONCLUSIONS: Pretreatment PSR index scores of 4 were a strong indicator of
periodontal access surgery needs in untreated dentition sextants but markedly
overestimated surgical access needs remaining after completion of non-surgical
periodontal therapy. These findings raise questions about the usefulness of
pretreatment PSR evaluations for estimating potential periodontal access surgery
needs in patients to be initially treated with non-surgical periodontal therapy.
PMID- 28517977
TI - Injectable chelate-setting hydroxyapatite cement prepared by using chitosan
solution: Fabrication, material properties, biocompatibility, and
osteoconductivity.
AB - An injectable chelate-setting hydroxyapatite cement (IP6-HAp), formed by chelate
bonding capability of inositol phosphate (IP6), was developed. The effects of
ball-milling duration of starting HAp powder and IP6 concentration on the
material properties such as injectability and mechanical strength of the cement
were examined. The cement powder was prepared by ball-milling the as-synthesized
HAp powder for 5 min using ZrO2 beads with a diameter of 10 mm, followed by
another 60 min with ZrO2 beads with a diameter of 2 mm, and thereafter surface
modified with 5000 ppm of IP6 solution. Injectable cement was then fabricated
with this HAp powder and 2.5 mass% chitosan as a mixing solution, with a setting
time of 36.3 +/- 4.7 min and a compressive strength of 19.0 +/- 2.1 MPa. The IP6
HAp cements prepared with chitosan showed favorable biocompatibility in vitro
using an osteoblast cell model, and osteoconductivity in vivo using a pig tibia
model.
PMID- 28517976
TI - Fabrication of micropatterns on polypropylene films via plasma pretreatment
combined with UV-initiated graft polymerization.
AB - In this study, micropatterns on polypropylene films were fabricated via plasma
pretreatment and UV-initiated graft polymerization. Firstly, radio-frequency
plasma, which does not significantly influence bulk attributes of substrates due
to limited penetration depth, was utilized to activate polypropylene films. Then,
different sizes of micropatterns of poly(hydroxyethyl methacrylate) (PHEMA) were
fabricated on the polypropylene films via UV-initiated graft polymerization of
hydroxyethyl methacrylate by using photo-masks. Scanning electron microscopy,
atomic force microscopy, X-ray photoelectron spectroscopy, and contact angle (CA)
were employed to characterize changes of pristine polypropylene films and
modified ones in surface morphology, roughness, hydrophilicity, free energy and
the surface chemical composition. All of these confirmed the successful grafting
of different sizes of PHEMA micropatterns on the polypropylene surface.
Furthermore, the influence of PHEMA micropatterns on cell proliferation and
cytotoxicity was evaluated in vitro. Analysis of cell behaviour indicated that
PHEMA micropatterns of the appropriate size can promote cellular adhesion and
proliferation, and the PHEMA-micropatterned polypropylene films had good
biocompatibility. The approach presented here provides an alternative to
synthesize on the surface of polypropylene films' micropatterns with the aim of
using them in a diverse array of applications.
PMID- 28517978
TI - The effect of carbon nanoparticles on biological properties of polyester
nanocomposites.
AB - The aim of present study was to determine the hemocompatibility, cellular
response of endothelial cells and bacterial adhesion to a new polyester
nanocomposite. The carbon nanoparticle nanocomposite was prepared via in situ
polymerization of monomers to obtain material of hardness 55 Sh D similar to
polyurethanes used in medical applications, for example, in heart-assisting
devices. The carbon nanoparticle-containing polyester exhibits markedly reduced
bacterial colonization, as compared to commercially available polyurethanes.
Further the nanocomposite possesses markedly improved hemocompatibility, as
determined by flow cytometry, and robust endothelialization. Possible
explanations for these beneficial properties include surface nanoroughness of
carbon nanoparticle-containing nanocomposites and presence of fatty acid
sequences within polymer structure.
PMID- 28517979
TI - Cell-type deconvolution in epigenome-wide association studies: a review and
recommendations.
AB - A major challenge faced by epigenome-wide association studies (EWAS) is cell-type
heterogeneity. As many EWAS have already demonstrated, adjusting for changes in
cell-type composition can be critical when analyzing and interpreting findings
from such studies. Because of their importance, a great number of different
statistical algorithms, which adjust for cell-type composition, have been
proposed. Some of the methods are 'reference based' in that they require a priori
defined reference DNA methylation profiles of cell types that are present in the
tissue of interest, while other algorithms are 'reference free.' At present,
however, it is unclear how best to adjust for cell-type heterogeneity, as this
may also largely depend on the type of tissue and phenotype being considered.
Here, we provide a critical review of the major existing algorithms for
correcting cell-type composition in the context of Illumina Infinium Methylation
Beadarrays, with the aim of providing useful recommendations to the EWAS
community.
PMID- 28517980
TI - Identification of prognostic and subtype-specific potential miRNAs in thymoma.
AB - AIM: We performed a study to identify the role of microRNA in thymoma. PATIENTS &
METHODS: One hundred twenty-three thymoma patients with clinical information and
miRNA expression data from The Cancer Genome Atlas were included in the study.
Comprehensive bioinformatics analysis was integrated in our analysis. RESULTS &
CONCLUSION: Seven miRNAs were found to be associated with overall survival (p <
0.001). Another four miRNAs were found to be associated with disease-free
survival (p < 0.001). Type C thymoma can be distinguished from nontype C thymoma
by miRNAs. Interestingly, seven miRNAs showed both prognostic and subtype
specific potential. Our findings suggest that miRNAs can be used for prognostic
prediction and subtype stratification.
PMID- 28517981
TI - A systematic review of studies of DNA methylation in the context of a weight loss
intervention.
AB - AIM: Obesity results from the interaction of genetic and environmental factors,
which may involve epigenetic mechanisms such as DNA methylation (DNAm). MATERIALS
& METHODS: We have followed the PRISMA protocol to select studies that analyzed
DNAm at baseline and end point of a weight loss intervention using either
candidate-locus or genome-wide approaches. RESULTS: Six genes displayed weight
loss associated DNAm across four out of nine genome-wide studies. Weight loss is
associated with significant but small changes in DNAm across the genome, and
weight loss outcome is associated with individual differences in baseline DNAm at
several genomic locations. CONCLUSION: The identified weight loss associated DNAm
markers, especially those showing reproducibility across different studies,
warrant validation by further studies with robust design and adequate power.
PMID- 28517982
TI - Data Sharing and the Idea of Ownership.
AB - Ideas about ownership are sometimes used in discussions of data sharing in
personalised medicine. Personal health data are thought by many to be 'theirs'.
Paradoxically, personalised medicine (at least in the context of genomics) relies
on the aggregation of private data into a dataset that is held as a form of
knowledge commons. When the notions of private and common property that lie
behind this discourse are made explicit we can use thinking about the
justifications and jurisprudence of property both to clarify the persuasiveness
and limits of such claims, and also how they differ from other principles that
are at stake in the interplay between individual and collective goods in the
delivery of personalised medicine. This shows that ownership might more plausibly
lie with health professionals than patients. In a socialised medicine system,
such as the NHS, such professionals are agents of the state and ownership would
lie with the commons rather than any individual. Common rather than private
ownership of genomic information may be more appropriate.
PMID- 28517984
TI - Personalised Medicine Approaches to Screening and Prevention.
AB - One of the promised benefits of 'personalised' medicine is that it will have a
positive impact on disease screening and prevention, by enabling more person
specific estimates of risk, and hence more personalised strategies for screening
and risk reduction. This article summarises some of the areas in which these
approaches are already being implemented, but also outlines some of the potential
difficulties and limitations - and challenges the assumption that 'personalised'
approaches are necessarily superior for prevention and screening.
PMID- 28517983
TI - Personalised Medicine and the Economy of Biotechnological Promise.
AB - Rather than seek to distinguish hype from legitimate promise, it may be more
helpful to think about personalised medicine as embodying a promissory economy
which serves both to mobilize resources for research and - partly at least - to
determine the ends to which that research is directed. Personalised medicine is a
development of the larger promissory economy of medical biotechnology. As such,
it systematically conflates public benefit with the pursuit of commercial and
especially pharmaceutical interests. Consequently, research and development in
personalised medicine tends to favour the production of expensive new treatments
over unprofitable forms of prevention or more effective use of older therapies. A
rebalancing of research priorities is needed to favour the pursuit of public
benefit, even when it does not deliver private profits. This will in turn require
sustained reflection, self-criticism and often self-denial on the part of public
research funders and the scientists they support.
PMID- 28517985
TI - Personalised Medicine: The Promise, the Hype and the Pitfalls.
AB - In engaging critically with personalised medicine and mapping pitfalls which mark
its progress this project aims to stimulate conversations which deal
intelligently with controversies for the sake of consensus. We aim to ask the
ethical questions which will lead to the improvement of healthcare and we take an
open-minded approach to finding answers to them over time. What is or should be
meant by 'personalised medicine' is a major theme of this issue. It is a debate
bound up with question of both values in the sense of ethical reflection and
value in the sense of economic return. This editorial discusses and interrelates
the articles of the issue under four headings: the promise and the hype of
personalised medicine; the human person and the communication of risk; data
sharing and participation; value, equity and power. A key intention throughout is
to provoke discourse and debate, to identify aspirations which are more grounded
in myth or hype than reality and to challenge them; and to identify focussed,
practical questions which need further examination.
PMID- 28517987
TI - The Human Dimension: Putting the Person into Personalised Medicine.
AB - Technological advances enabling us to personalise medical interventions at the
biological level must be matched by parallel advances in how we support the
informed choices essential to patient and public participation. We cannot take
participation for granted. To be truly personalised, medicine must take account
of the perceptions and capabilities that shape participation. To do this, we need
a better understanding of how people perceive personalised medicine and how they
judge its value and risks. To realise the promise of 4P medicine we need to
personalise at the psychosocial as well as biological dimension, putting the
person into personalised medicine.
PMID- 28517986
TI - From Rosalind Franklin to Barack Obama: Data Sharing Challenges and Solutions in
Genomics and Personalised Medicine.
AB - The collection, storage and use of genomic and clinical data from patients and
healthy individuals is a key component of personalised medicine enterprises such
as the Precision Medicine Initiative, the Cancer Moonshot and the 100,000 Genomes
Project. In order to maximise the value of this data, it is important to embed a
culture within the scientific, medical and patient communities that supports the
appropriate sharing of genomic and clinical information. However, this aspiration
raises a number of ethical, legal and regulatory challenges that need to be
addressed. The Global Alliance for Genomics and Health, a worldwide coalition of
researchers, healthcare professionals, patients and industry partners, is
developing innovative solutions to support the responsible and effective sharing
of genomic and clinical data. This article identifies the challenges that a data
sharing culture poses and highlights a series of practical solutions that will
benefit patients, researchers and society.
PMID- 28517990
TI - Risk and Benefit in Personalised Medicine: An End User View.
AB - Personalised, or stratified, medicine is creating opportunities for the
development of targeted therapies for many hitherto unmet clinical needs. For
patients and families this is a cause for optimism. But it is unlikely that these
novel therapies will provide complete cures. Rather they will address some but
not all symptoms of a condition. In such circumstances, early engagement with
patients and families will ensure that developments are targeted at those aspects
of a condition which really matter, not just those that are easy to count. This
will make the development process more efficient, and improve the likelihood that
patients will be able to access therapies if the development process is
successful.
PMID- 28517988
TI - The Promise and the Hype of 'Personalised Medicine'.
AB - Personalised medicine is widely considered as the way of the future for medicine.
However, progress in cancer, with a few outstanding exceptions, has fallen below
expectations because of the challenges of tumour heterogeneity and clonal
evolution. In both benign and malignant disease, diseases caused by single
genetic alterations are more amenable to precision medicine approaches. However,
most common diseases are caused by a complex interplay of multiple genetic and
environmental factors making personalised medicine far more challenging. The
current optimism for personalised medicine is distorting clinical consultations,
resource allocation and research funding prioritisation. A research active
clinician must act both as an agent of change and development, and as a
communicator of realism. Thus personalised medicine that includes a sober
appreciation of what genomics can achieve, together with continued focus on the
individual as a person not just as a genome, will contribute to further
improvements in health and healthcare.
PMID- 28517989
TI - Economics of Cancer Medicines: For Whose Benefit?
AB - Although new cancer drugs are continually getting approved and used, the value
that these drugs add is very debatable. Because of the skyrocketing cost of the
new drugs, each new approval represents a multibillion market. However, unlike
other branches of economics, cancer drugs are intricately associated with socio
political issues, emotional overlay, public pressure, industry manipulation and
propaganda. In this article, we review the value added by new cancer drugs and
examine the socio-political agenda around them with highlights on the increasing
gulf between high-income and low-middle income countries regarding the
affordability to these drugs. Finally, we also suggest a way forward to address
this highly complex issue.
PMID- 28517991
TI - Self-Knowledge and Risk in Stratified Medicine.
AB - This article considers why and how self-knowledge is important to communication
about risk and behaviour change by arguing for four claims. First, it is doubtful
that genetic knowledge should properly be called 'self-knowledge' when its
ordinary effects on self-motivation and behaviour change seem so slight. Second,
temptations towards a reductionist, fatalist, construal of persons' futures
through a 'molecular optic' should be resisted. Third, any plausible effort to
change people's behaviour must engage with cultural self-knowledge, values and
beliefs, catalysed by the communication of genetic risk. For example, while a
Judaeo-Christian notion of self-knowledge is distinctively theological, people's
self-knowledge is plural in its insight and sources. Fourth, self-knowledge is
found in compassionate, if tense, communion which yields freedom from determinism
even amidst suffering. Stratified medicine thus offers a newly precise kind of
humanising health care through societal solidarity with the riskiest. However,
stratification may also mean that molecularly unstratified, 'B' patients'
experience involves accentuated suffering and disappointment, a concern requiring
further research.
PMID- 28517992
TI - Equity and Value in 'Precision Medicine'.
AB - Precision medicine carries huge potential in the treatment of many diseases,
particularly those with high-penetrance monogenic underpinnings. However,
precision medicine through genomic technologies also has ethical implications. We
will define allocative, personal, and technical value ('triple value') in
healthcare and how this relates to equity. Equity is here taken to be implicit in
the concept of triple value in countries that have publicly funded healthcare
systems. It will be argued that precision medicine risks concentrating resources
to those that already experience greater access to healthcare and power in
society, nationally as well as globally. Healthcare payers, clinicians, and
patients must all be involved in optimising the potential of precision medicine,
without reducing equity. Throughout, the discussion will refer to the NHS
RightCare Programme, which is a national initiative aiming to improve value and
equity in the context of NHS England.
PMID- 28517993
TI - Your DNA, Your Say.
AB - Genomic and medical data sharing is pivotal if the promise of genomic medicine is
to be fully realised. Social scientists working in the genomics arena ask the
public 'how is the technology working for you?' Empirical studies on attitudes,
values and beliefs are incredibly valuable; they offer a voice from those who
are, or will be, directly affected. This is paramount if personalised medicine is
to be truly personal. An International attitude study, Your DNA, Your Say, uses
film to provide background information and an online survey to gather public
views on donating one's own personal DNA and medical data for use by others. In
this paper the rationale to the project is introduced together with an overview
of the survey and film design. The project has been translated into multiple
languages and the results will be used in policy for the Global Alliance for
Genomics and Health.
PMID- 28517994
TI - Dr. Lynne Anne Fulton (1949-2017).
PMID- 28517995
TI - "Moments".
PMID- 28517996
TI - Prevalence of potential smoking-related conditions among tobacco users in the
emergency department and their perception that their visit may be smoking-related
- ERRATUM.
PMID- 28517998
TI - To Publish, Publish, and Publish Again.
PMID- 28517999
TI - Venous Gas Emboli and Ambulation at 4.3 psia.
AB - INTRODUCTION: Ambulation during extravehicular activity on Mars may increase the
risk of decompression sickness through enhanced bubble formation in the lower
body. HYPOTHESES: walking effort (ambulation) before an exercise-enhanced
denitrogenation (prebreathe) protocol at 14.7 psia does not increase the
incidence of venous gas emboli (VGE) at 4.3 psia, but does increase incidence if
performed after tissues become supersaturated with nitrogen at 4.3 psia. METHODS:
VGE results from 45 control subjects who performed exercise prebreathe without
ambulation before or during a 4-h exposure to 4.3 psia were compared to 21
subjects who performed the same prebreathe but ambulated before and during the
hypobaric exposure (Group I) and to 41 subjects who only ambulated before the
hypobaric exposure (Group II). Monitoring for VGE in the pulmonary artery was for
4 min at about 12-min intervals using precordial Doppler ultrasound (2.5 mHz).
Detected VGE were assigned a categorical grade from I to IV. The detection of
Grade III or IV was classified as "high VGE grade." RESULTS: The incidence of
high VGE grade for Group I (57%) was greater than the control (17%) and Group II
(15%). The incidence of pain-only decompression sickness was greater for Group I
(20%) than the control (0%) and Group II (5%). CONCLUSIONS: High-grade VGE are
increased by mild ambulation conducted under a supersaturated state (Group I vs.
II); however, no increase was observed with mild ambulation during the saturated
state alone (control vs. Group II).Conkin J, Pollock NW, Natoli MJ, Martina SD,
Wessell JH III, Gernhardt ML. Venous gas emboli and ambulation at 4.3 psia.
Aerosp Med Hum Perform. 2017; 88(4):370-376.
PMID- 28518000
TI - Comparison of Simulated Microgravity and Hydrostatic Pressure for Chondrogenesis
of hASC.
AB - BACKGROUND: Cartilage tissue engineering is a growing field due to the lack of
regenerative capacity of native tissue. The use of bioreactors for cartilage
tissue engineering is common, but the results are controversial. Some studies
suggest that microgravity bioreactors are ideal for chondrogenesis, while others
show that mimicking hydrostatic pressure is crucial for cartilage formation. A
parallel study comparing the effects of loading and unloading on chondrogenesis
has not been performed. METHODS: The goal of this study was to evaluate
chondrogenesis of human adipose-derived stem cells (hASC) under two different
mechanical stimuli relative to static culture: microgravity and cyclic
hydrostatic pressure (CHP). Pellets of hASC were cultured for 14 d under
simulated microgravity using a rotating wall vessel bioreactor or under CHP (7.5
MPa, 1 Hz, 4 h . d-1) using a hydrostatic pressure vessel. RESULTS: We found that
CHP increased mRNA expression of Aggrecan, Sox9, and Collagen II, caused a
threefold increase in sulfated glycosaminoglycan production, and resulted in
stronger vimentin staining intensity and organization relative to microgravity.
In addition, Wnt-signaling patterns were altered in a manner that suggests that
simulated microgravity decreases chondrogenic differentiation when compared to
CHP. DISCUSSION: Our goal was to compare chondrogenic differentiation of hASC
using a microgravity bioreactor and a hydrostatic pressure vessel, two commonly
used bioreactors in cartilage tissue engineering. Our results indicate that CHP
promotes hASC chondrogenesis and that microgravity may inhibit hASC
chondrogenesis. Our findings further suggest that cartilage formation and
regeneration might be compromised in space due to the lack of mechanical
loading.Mellor LF, Steward AJ, Nordberg RC, Taylor MA, Loboa EG. Comparison of
simulated microgravity and hydrostatic pressure for chondrogenesis of hASC.
Aerosp Med Hum Perform. 2017; 88(4):377-384.
PMID- 28518001
TI - Propranolol Effects on Decompression Sickness in a Simulated DISSUB Rescue in
Swine.
AB - INTRODUCTION: Disabled submarine (DISSUB) survivors may face elevated CO2 levels
and inert gas saturation, putting them at risk for CO2 toxicity and decompression
sickness (DCS). Propranolol was shown to reduce CO2 production in an experimental
DISSUB model in humans but its effects on DCS in a DISSUB rescue scenario are
unknown. A 100% oxygen prebreathe (OPB) reduces DCS incidence and severity and is
incorporated into some DISSUB rescue protocols. We used a swine model of DISSUB
rescue to study the effect of propranolol on DCS incidence and mortality with and
without an OPB. METHODS: In Experiment 1, male Yorkshire Swine (70 kg) were
pressurized to 2.8 ATA for 22 h. Propranolol 1.0 mg . kg-1 (IV) was administered
at 21.25 h. At 22 h, the animal was rapidly decompressed and observed for DCS
type, onset time, and mortality. Experimental animals (N = 21; 69 +/- 4.1 kg),
PROP1.0, were compared to PROP1.0-OPB45 (N = 8; 69 +/- 2.8 kg) with the same dive
profile, except for a 45 min OPB prior to decompression. In Experiment 2, the
same methodology was used with the following changes: swine pressurized to 2.8
ATA for 28 h; experimental group (N = 25; 67 +/- 3.3 kg), PROP0.5 bis,
propranolol 0.5 mg . kg-1 bis (twice) (IV) was administered at 22 h and 26 h.
Control animals (N = 25; 67 +/- 3.9 kg) received normal saline. RESULTS: OPB
reduced mortality in PROP1.0-OBP45 compared to PROP1.0 (0% vs. 71%). PROP0.5 bis
had increased mortality compared to CONTROL (60-% vs. 4%). DISCUSSION:
Administration of beta blockers prior to saturation decompression appears to
increase DCS and worsen mortality in a swine model; however, their effects in
bounce diving remain unknown.Forbes AS, Regis DP, HallAA, Mahon RT, Cronin WA.
Propranolol effects on decompression sickness in a simulated DISSUB rescue in
swine. Aerosp Med Hum Perform. 2017; 88(4):385-391.
PMID- 28518002
TI - Cognitive Evaluation of Israeli Air Force Pilot Cadets.
AB - OBJECTIVE: In aviation psychology, there is a constant need for the cognitive
evaluation of pilots as part of operational fitness and safety criteria. METHODS:
A cross-sectional study with comparison between the performance of Israeli Air
Force pilot cadets (N = 318) and U.S. Air Force pilot training candidates (N =
512) as assessed by a cognitive battery was undertaken. The data of the
comparison group was collected from Callister, King, and Retzlaff, as published
in 1996. RESULTS: In general, the means in the three components composing the
battery-speed, accuracy, and throughput variables-indicated that the Israeli Air
Force pilot cadets' scores were higher than those of the U.S. Air Force pilot
candidates' scores in 50 of 53 variables. Nonsignificant differences were found
in Accuracy of shifting attention-arrow color (SATAC), pathfinder-combined (PFC),
and pathfinder-letter (PFL). CONCLUSIONS: The difference in performance between
the two groups may be due to differences in population characteristics. However,
these results need to be considered cautiously, as the groups were sampled at a
sizeable time gap (1996 for the U.S. Air Force vs. 2013 for the Israeli Air
Force), with each time period characterized by different cultural and
technological influences.Gordon S, Goren C, Carmon E, Shelef L. Cognitive
evaluation of Israeli Air Force pilot cadets. Aerosp Med Hum Perform. 2017;
88(4):392-398.
PMID- 28518003
TI - Caffeine Consumption Among Naval Aviation Candidates.
AB - INTRODUCTION: Education frequently dictates students need to study for prolonged
periods of time to adequately prepare for examinations. This is especially true
with aviation preflight indoctrination (API) candidates who have to assimilate
large volumes of information in a limited amount of time during API training. The
purpose of this study was to assess caffeine consumption patterns (frequency,
type, and volume) among naval aviation candidates attending API to determine the
most frequently consumed caffeinated beverage and to examine if the consumption
of a nonenergy drink caffeinated beverage was related to energy drink
consumption. METHODS: Data were collected by means of an anonymous 44-item survey
administered and completed by 302 students enrolled in API at Naval Air Station
Pensacola, FL. RESULTS: Results indicated the most frequently consumed
caffeinated beverage consumed by API students was coffee (86.4%), with daily
coffee consumption being approximately 28% and the most frequent pattern of
consumption being 2 cups per day (85%). The least frequently consumed caffeinated
beverages reported were energy drinks (52%) and energy shots (29.1%). The present
study also found that the consumption patterns (weekly and daily) of caffeinated
beverages (coffee and cola) were positively correlated to energy drink
consumption patterns. DISCUSSION: Naval aviation candidates' consumption of
caffeinated beverages is comparable to other college and high school cohorts.
This study found that coffee and colas were the beverages of choice, with energy
drinks and energy shots being the least frequently reported caffeinated beverages
used. Additionally, a relationship between the consumption of caffeinated
beverages and energy drinks was identified.Sather TE, Williams RD, Delorey DR,
Woolsey CL. Caffeine consumption among naval aviation candidates. Aerosp Med Hum
Perform. 2017; 88(4):399-405.
PMID- 28518004
TI - Middle Ear Barotrauma in Student Pilots.
AB - INTRODUCTION: The present study reports the clinical features of middle ear
barotrauma in student pilots in the Republic of Korea Air Force. METHODS: The
authors reviewed medical records of student pilots with barotrauma. The grade of
barotrauma was assigned using Teed's classification. This study included nasal
symptoms, endoscopic findings of the nasal cavity, and clinical course (duration,
recurrence). The relationship between middle ear barotrauma and the nasal airway
was also evaluated. RESULTS: There were 57 cases in 51 pilots included. There
were 49 cases (86.0%) that showed unilateral disease and 4 subjects experienced
relapse. Two subjects (3.9%) had chronic rhinosinusitis and four subjects (7.8%)
had allergic rhinitis. Ear fullness was reported in all cases, while hearing loss
and persistent ear pain were reported in 3 cases (5.3%) and 19 cases (33.3%),
respectively. Stuffy nose (26 cases, 45.6%) and rhinorrhea (24 cases, 42.1%) were
relatively common. Most cases were Grade 0 (23 cases, 40.3%) or Grade III (27
cases, 47.4%) according to Teed's classification. Septal deviation was observed
in 12 cases (21.0%), while turbinate hypertrophy was seen in 53 cases (93.0%) and
increased nasal discharge in 33 cases (57.9%). The grade of barotrauma varied
significantly according to the severity of turbinate hypertrophy and nasal
discharge. The mean duration of disease was 6.8 d. DISCUSSION: Nasal symptoms and
endoscopic findings showed some association with the grade and duration of
barotrauma. Most cases resolved within a week; however, barotrauma showed
persistence or relapse in some cases.Sohn JH, Cho KR. Middle ear barotrauma in
student pilots. Aerosp Med Hum Perform. 2017; 88(4):406-412.
PMID- 28518005
TI - Safety Considerations for Medical Staff and Patients Who Fly Over Water in a
Helicopter for Work or Recreation.
AB - BACKGROUND: Around 25% of people involved in a helicopter accident in water do
not survive. From time to time, physicians and their medical staff are required
to fly over water in a helicopter to attend one or more seriously ill patients.
Many will have had little or no experience of the issues involved if the
helicopter has an accident in the water. Also as Family Practitioners,
Aeromedical Examiners, and Flight Surgeons, they are asked to provide advice to
patients, travel agents, and airline booking agents about whether an overwater
helicopter flight is advisable or not. METHOD: From 50 yr of helicopter accident
evidence in the scientific literature, government agency reports, and statistics
from the military safety centers and the offshore oil industry, the critical
hazards involved and risks to medical staff and their patients have been
identified. RESULTS: Patients most at risk are those who suffer from
cardiovascular or respiratory disease, have physical disabilities, have a very
large body size, and anyone who is a non-swimmer. Medical staff are at risk if
they are not familiar with the procedure for escape from a flooded inverted cabin
and difficulties after escape from the fuselage with life jackets, life rafts,
and sometimes the necessity to swim ashore. CONCLUSIONS: With 50 yr of hindsight,
many of the deaths were preventable, and many lives can be saved if a series of
very simple mental and physical preventive actions are taken by anyone stepping
on to a helicopter that flies over water.Brooks CJ, MacDonald CV. Safety
considerations for medical staff and patients who fly over water in a helicopter
for work or recreation. Aerosp Med Hum Perform. 2017; 88(4):413-417.
PMID- 28518007
TI - Patient-Centric Side Effect Risk Assessment for Medications Used During
Aeromedical Evacuations.
AB - BACKGROUND: The U.S. Air Force performs more than 6000 aeromedical transport
flights annually, both internationally and domestically. Many of these flights
include patients requiring pain relief medications. The risk of side effects from
such medications administered at altitude is unknown, but understanding these
risks is vital when selecting the safest pain management strategies to achieve
optimal postflight outcomes. METHODS: Using an evidence-based medication side
effect risk assessment model, we compared our patient-centric approach to an
aircrew-centric approach using medications approved for use in U.S. Navy aircrew.
We then determined the patient-centric side effect risk of medications commonly
used during Air Force aeromedical evacuation (AE). RESULTS: The patient-centric
approach to medication side effect risk assessment demonstrates that the majority
of medications currently approved for use during AE have an acceptable side
effect risk for the patient (18/22, 82%). Four approved drugs displayed
significantly elevated patient risk, with risk scores between 2.0- and 3.2-fold
greater than the statistically determined upper allowable ("acceptable") limit
and between 1.2- and 2.0-fold above the upper control ("tolerable") limit.
DISCUSSION: Our results suggest that pain management strategies during AE should
be tailored individually to minimize the risk associated with pain medications
administered en route.Huntsberger SA, Butler WP, Chapleau RR. Patient-centric
side effect risk assessment for medications used during aeromedical evacuations.
Aerosp Med Hum Perform. 2017; 88(4):423-426.
PMID- 28518006
TI - Cooling Effects of Wearer-Controlled Vaporization for Extravehicular Activity.
AB - INTRODUCTION: The extravehicular activity suit currently used by the United
States in space includes a liquid cooling and ventilation garment (LCVG) that
controls thermal conditions. Previously, we demonstrated that self-perspiration
for evaporative cooling (SPEC) garment effectively lowers skin temperature
without raising humidity in the garment. However, the cooling effect is delayed
until a sufficient dose of water permeates and evaporates. In the present study,
we hypothesized that wearer-controlled vaporization improves the cooling effect.
METHODS: Six healthy subjects rode a cycle ergometer under loads of 30, 60, 90,
and 120 W for durations of 3 min each. Skin temperature and humidity on the back
were measured continuously. Subjects wore and tested three garments: 1) a spandex
garment without any cooling device (Normal); 2) a simulated LCVG (s-LCVG) or
spandex garment knitted with a vinyl tube for flowing and permeating water; and
3) a garment that allowed wearer-controlled vaporization (SPEC-W). RESULTS: The
use of s-LCVG reduced skin temperature by 1.57 +/- 0.14 degrees C during 12 min
of cooling. Wearer-controlled vaporization of the SPEC-W effectively and
significantly lowered skin temperature from the start to the end of cycle
exercise. This decrease was significantly larger than that achieved using s-LCVG.
Humidity in the SPEC-W was significantly lower than that in s-LCVG. DISCUSSION:
This preliminary study suggests that SPEC-W is effective in lowering skin
temperature without raising humidity in the garment. The authors think it would
be useful in improving the design of a cooling system for extravehicular
activity.Tanaka K, Nagao D, Okada K, Nakamura K. Cooling effects of wearer
controlled vaporization for extravehicular activity. Aerosp Med Hum Perform.
2017; 88(4):418-422.
PMID- 28518008
TI - Latent Presentation of Decompression Sickness After Altitude Chamber Training in
an Active Duty Flier.
AB - BACKGROUND: Decompression sickness (DCS) is a potential danger and risk for both
divers and aircrew alike. DCS is also a potential side effect of altitude
(hypobaric) chamber training as well and can present long after training occurs.
Literature review shows that altitude chamber induced DCS has approximately a
0.25% incidence. CASE REPORT: A 32-yr-old, active duty military member developed
symptoms of DCS 3 h after his hypobaric chamber training. Unfortunately, he did
not seek treatment for DCS until 48 h after the exposure. His initial treatment
included ground level oxygen therapy for 30 min at 12 L of oxygen per minute
using a nonrebreathing mask. He achieved complete symptom resolution and was
returned to duty. However, 12 d after his initial Flight Medicine evaluation, the
patient returned complaining of a right temporal headache, multijoint pains, and
fatigue. He was treated in the hyperbaric chamber and had complete resolution of
symptoms. He was returned to flying status and 5 mo later denied any return of
symptoms. DISCUSSION: Hypobaric chamber familiarity training is a requirement for
all military aircrew personnel to allow them assess their ability to identify
symptoms of hypoxia. This training method is not only costly to maintain, but it
also places aircrew and chamber technicians at risk for potential long-term side
effects from failed recompression treatment of DCS. We are presenting a case of
recurrent DCS symptoms 12 d after initial ground level oxygen therapy.Gentry J,
Rango J, Zhang J, Biedermann S. Latent presentation of decompression sickness
after altitude chamber training in an active duty flier. Aerosp Med Hum Perform.
2017; 88(4):427-430.
PMID- 28518009
TI - Aeromedical Evacuation Using Extra Corporeal Life Support After Resuscitated
Cardiac Arrest.
AB - BACKGROUND: Extra corporeal life support (ECLS) is presently first line therapy
for refractory cardiogenic shock. Mobile circulatory support teams implant ECLS
or extra corporeal membrane oxygenation (ECMO) in patients in the hospital
without circulatory support. These patients are then transported to specialized
centers. Here we report a case of sending a mobile circulatory support team
abroad, followed by air ambulance evacuation, which, to our knowledge, has never
been used as part of medical assistance abroad. CASE REPORT: In June, during a
holiday in Turkey, a 56-yr-old woman complained about chest pain. She had a
cardiac arrest and was resuscitated with no no-flow time in the local hospital.
ECG showed ST segment elevation. Medic'Air International medical assistance
(Paris, France) contacted the hospital, which was not equipped with
coronarography or cardiac ultrasound and the local treating doctor refused
transfer of the patient to another facility. A medical team completed by a
cardiothoracic surgeon and a perfusionist went from Paris to the patient's
bedside by air ambulance. They implemented the ECLS and successfully repatriated
the patient to her home country (Belgium). The patient's condition improved, she
neurologically improved, and returned home on the 14th day. DISCUSSION: Possible
indications for ECLS repatriations firstly take into account recognized ECLS
indications and case-by-case discussions on the evaluation of inadequacy of the
health facilities and risk-benefit balance. In international medical assistance,
this case's description is an example of repatriation for patients who previously
could not be transferred due to high risk of such intervention.Gerard D, Raffin
H, Lebreton G. Aeromedical evacuation using extra corporeal life support after
resuscitated cardiac arrest. Aerosp Med Hum Perform. 2017; 88(4):431-433.
PMID- 28518010
TI - Mechanical Simulators of the Cardiovascular System: An Alternative to Research
Subjects and Patients.
PMID- 28518012
TI - You're the Flight Surgeon.
AB - Milner MR. You're the flight surgeon: an unusual case of pharyngitis. Aerosp Med
Hum Perform. 2017; 88(4):439-442.
PMID- 28518011
TI - You're the Flight Surgeon.
AB - Ensley D. You're the flight surgeon: green laser event. Aerosp Med Hum Perform.
2017; 88(4):437-439.
PMID- 28518013
TI - Thomas R. White, M.D., Doolittle Raider Flight Surgeon.
PMID- 28518014
TI - Erratum.
PMID- 28518015
TI - This Month in Aerospace Medicine History.
PMID- 28518016
TI - This Month in Aerospace Medicine History.
PMID- 28518017
TI - Enterocytozoon bieneusi Microsporidiosis in Stem Cell Transplant Recipients
Treated with Fumagillin
AB - Enterocytozoon bieneusi microsporidiosis is an emerging disease in
immunocompromised patients. We report 2 cases of this disease in allogeneic
hematopoietic stem cell transplant patients successfully treated with fumagillin.
Thrombocytopenia occurred but without major adverse events. Modifications of
immunosuppression could be avoided when E. bieneusi is rapidly identified and
fumagillin therapy is started promptly.
PMID- 28518018
TI - Penicillin Resistance of Nonvaccine Type Pneumococcus before and after PCV13
Introduction, United States.
AB - Introduction of 13-valent pneumococcal conjugate vaccine in the United States was
not associated with a significant change in prevalence of penicillin resistance
in nonvaccine type serotypes because of the variable success of highly resistant
serotypes. Differences in regional serotype distribution and serotype-specific
resistance contributed to geographic heterogeneity of penicillin resistance.
PMID- 28518019
TI - Ebola Virus Imported from Guinea to Senegal, 2014.
AB - In March 2014, the World Health Organization declared an outbreak of Ebola virus
disease in Guinea. In August 2014, a case caused by virus imported from Guinea
occurred in Senegal, most likely resulting from nonsecure funerals and travel.
Preparedness and surveillance in Senegal probably prevented secondary cases.
PMID- 28518021
TI - Endemic Hantavirus in Field Voles, Northern England.
AB - We report a PCR survey of hantavirus infection in an extensive field vole
(Microtus agrestis) population present in the Kielder Forest, northern England. A
Tatenale virus-like lineage was frequently detected (~17% prevalence) in liver
tissue. Lineages genetically similar to Tatenale virus are likely to be endemic
in northern England.
PMID- 28518020
TI - Outbreaks of Tilapia Lake Virus Infection, Thailand, 2015-2016.
AB - During 2015-2016, several outbreaks of tilapia lake virus infection occurred
among tilapia in Thailand. Phylogenetic analysis showed that the virus from
Thailand grouped with a tilapia virus (family Orthomyxoviridae) from Israel. This
emerging virus is a threat to tilapia aquaculture in Asia and worldwide.
PMID- 28518023
TI - Zika Virus-Associated Cognitive Impairment in Adolescent, 2016.
AB - Incidence of neurologic manifestations associated with Zika virus infection has
been increasing. In 2016, neuropsychological and cognitive changes developed in
an adolescent after travel to a Zika virus-endemic area. Single-photon emission
computed tomography and neuropsychological testing raised the possibility that
Zika virus infection may lead to neuropsychiatric and cognitive symptoms.
PMID- 28518022
TI - High Frequency of Mayaro Virus IgM among Febrile Patients, Central Brazil.
AB - Mayaro virus (MAYV), an Aedes mosquito-borne alphavirus, is endemic to Brazil and
other South America countries. We investigated dengue- and chikungunya-negative
febrile patients visiting rural areas near Goiania, Goias, and found a high
proportion (55%) of MAYV IgM. Our findings suggest the presence of highly endemic
foci of MAYV in central Brazil.
PMID- 28518024
TI - Tick-Borne Encephalitis Virus in Ticks and Roe Deer, the Netherlands.
AB - We report the presence of tick-borne encephalitis virus (TBEV) in the
Netherlands. Serologic screening of roe deer found TBEV-neutralizing antibodies
with a seroprevalence of 2%, and TBEV RNA was detected in 2 ticks from the same
location. Enhanced surveillance and awareness among medical professionals has led
to the identification of autochthonous cases.
PMID- 28518025
TI - Rise in Group W Meningococcal Carriage in University Students, United Kingdom.
AB - MenACWY conjugate vaccination was recently introduced in the United Kingdom for
adolescents and young adults to reduce disease from infection by Neisseria
meningitidis group W. We conducted a cross-sectional meningococcal carriage study
in first-year UK university students. Despite 71% MenACWY vaccine coverage,
carriage of group W increased substantially.
PMID- 28518026
TI - Outbreak-Related Disease Burden Associated with Consumption of Unpasteurized
Cow's Milk and Cheese, United States, 2009-2014.
AB - The growing popularity of unpasteurized milk in the United States raises public
health concerns. We estimated outbreak-related illnesses and hospitalizations
caused by the consumption of cow's milk and cheese contaminated with Shiga toxin
producing Escherichia coli, Salmonella spp., Listeria monocytogenes, and
Campylobacter spp. using a model relying on publicly available outbreak data. In
the United States, outbreaks associated with dairy consumption cause, on average,
760 illnesses/year and 22 hospitalizations/year, mostly from Salmonella spp. and
Campylobacter spp. Unpasteurized milk, consumed by only 3.2% of the population,
and cheese, consumed by only 1.6% of the population, caused 96% of illnesses
caused by contaminated dairy products. Unpasteurized dairy products thus cause
840 (95% CrI 611-1,158) times more illnesses and 45 (95% CrI 34-59) times more
hospitalizations than pasteurized products. As consumption of unpasteurized dairy
products grows, illnesses will increase steadily; a doubling in the consumption
of unpasteurized milk or cheese could increase outbreak-related illnesses by 96%.
PMID- 28518027
TI - Measles Cases during Ebola Outbreak, West Africa, 2013-2106.
AB - The recent Ebola outbreak in West Africa caused breakdowns in public health
systems, which might have caused outbreaks of vaccine-preventable diseases. We
tested 80 patients admitted to an Ebola treatment center in Freetown, Sierra
Leone, for measles. These patients were negative for Ebola virus. Measles virus
IgM was detected in 13 (16%) of the patients.
PMID- 28518028
TI - Brucella neotomae Infection in Humans, Costa Rica.
AB - Several species of Brucella are known to be zoonotic, but B. neotomae infection
has been thought to be limited to wood rats. In 2008 and 2011, however, B.
neotomae was isolated from cerebrospinal fluid of 2 men with neurobrucellosis.
The nonzoonotic status of B. neotomae should be reassessed.
PMID- 28518029
TI - Influenza A(H9N2) Virus, Myanmar, 2014-2015.
AB - Routine surveillance of influenza A virus was conducted in Myanmar during 2014
2015. Influenza A(H9N2) virus was isolated in Shan State, upper Myanmar. Whole
genome sequencing showed that H9N2 virus from Myanmar was closely related to H9N2
virus of clade 4.2.5 from China.
PMID- 28518030
TI - Serologic and Molecular Evidence of Vaccinia Virus Circulation among Small
Mammals from Different Biomes, Brazil.
AB - Vaccinia virus (VACV) is a zoonotic agent that causes a disease called bovine
vaccinia, which is detected mainly in milking cattle and humans in close contact
with these animals. Even though many aspects of VACV infection have been
described, much is still unknown about its circulation in the environment and its
natural hosts/reservoirs. To investigate the presence of Orthopoxvirus antibodies
or VACV DNA, we captured small rodents and marsupials in 3 areas of Minas Gerais
state, Brazil, and tested their samples in a laboratory. A total of 336 animals
were tested; positivity ranged from 18.1% to 25.5% in the 3 studied regions
located in different biomes, including the Atlantic Forest and the Cerrado.
Analysis of nucleotide sequences indicated co-circulation of VACV groups I and
II. Our findings reinforce the possible role played by rodents and marsupials in
VACV maintenance and its transmission chain.
PMID- 28518031
TI - Clinical and Molecular Characteristics of Human Rotavirus G8P[8] Outbreak Strain,
Japan, 2014.
AB - During March-July 2014, rotavirus G8P[8] emerged as the predominant cause of
rotavirus gastroenteritis among children in Hokkaido Prefecture, Japan. Clinical
characteristics were similar for infections caused by G8 and non-G8 strains.
Sequence and phylogenetic analyses suggest the strains were generated by multiple
reassortment events between DS-1-like P[8] strains and bovine strains from Asia.
PMID- 28518032
TI - Isolated Case of Marburg Virus Disease, Kampala, Uganda, 2014.
AB - In September 2014, a single fatal case of Marburg virus was identified in a
healthcare worker in Kampala, Uganda. The source of infection was not identified,
and no secondary cases were identified. We describe the rapid identification,
laboratory diagnosis, and case investigation of the third Marburg virus outbreak
in Uganda.
PMID- 28518034
TI - Relative Risk for Ehrlichiosis and Lyme Disease in an Area Where Vectors for Both
Are Sympatric, New Jersey, USA.
PMID- 28518033
TI - Distribution and Quantitative Estimates of Variant Creutzfeldt-Jakob Disease
Prions in Tissues of Clinical and Asymptomatic Patients.
AB - In the United-Kingdom, ~1 of 2,000 persons could be infected with variant
Creutzfeldt-Jakob disease (vCJD). Therefore, risk of transmission of vCJD by
medical procedures remains a major concern for public health authorities. In this
study, we used in vitro amplification of prions by protein misfolding cyclic
amplification (PMCA) to estimate distribution and level of the vCJD agent in 21
tissues from 4 patients who died of clinical vCJD and from 1 asymptomatic person
with vCJD. PMCA identified major levels of vCJD prions in a range of tissues,
including liver, salivary gland, kidney, lung, and bone marrow. Bioassays
confirmed that the quantitative estimate of levels of vCJD prion accumulation
provided by PMCA are indicative of vCJD infectivity levels in tissues. Findings
provide critical data for the design of measures to minimize risk for iatrogenic
transmission of vCJD.
PMID- 28518035
TI - Angiostrongylus cantonensis Meningitis and Myelitis, Texas, USA.
AB - Infection with Angiostrongylus cantonensis roundworms is endemic in Southeast
Asia and the Pacific Basin. A. cantonensis meningitis and myelitis occurred in
summer 2013 in a child with no history of travel outside of Texas, USA.
Angiostrongyliasis is an emerging neurotropic helminthic disease in Texas and
warrants increased awareness among healthcare providers.
PMID- 28518036
TI - Sustainability of High-Level Isolation Capabilities among US Ebola Treatment
Centers.
AB - To identify barriers to maintaining and applying capabilities of US high-level
isolation units (HLIUs) used during the Ebola virus disease outbreak, during 2016
we surveyed HLIUs. HLIUs identified sustainability challenges and reported the
highly infectious diseases they would treat. HLIUs expended substantial resources
in development but must strategize models of sustainability to maintain
readiness.
PMID- 28518037
TI - Crimean-Congo Hemorrhagic Fever in Migrant Worker Returning from Oman to India,
2016.
AB - In January 2016, a migrant worker who returned home to India after becoming ill
in Oman was confirmed to have Crimean-Congo hemorrhagic fever (CCHF). Physicians
should include CCHF in the differential diagnosis for patients with hemorrhagic
signs and a history of recent travel to any area where CCHF is endemic or
prevalent.
PMID- 28518038
TI - Febrile Respiratory Illness Associated with Human Adenovirus Type 55 in South
Korea Military, 2014-2016
AB - An outbreak of febrile respiratory illness associated with human adenovirus
(HAdV) occurred in the South Korea military during the 2014-15 influenza season
and thereafter. Molecular typing and phylogenetic analysis of patient samples
identified HAdV type 55 as the causative agent. Emergence of this novel HAdV
necessitates continued surveillance in military and civilian populations.
PMID- 28518040
TI - Highly Pathogenic Avian Influenza Virus (H5N8) Clade 2.3.4.4 Infection in
Migratory Birds, Egypt.
AB - We isolated highly pathogenic avian influenza virus (H5N8) of clade 2.3.4.4 from
the common coot (Fulica atra) in Egypt, documenting its introduction into Africa
through migratory birds. This virus has a close genetic relationship with subtype
H5N8 viruses circulating in Europe. Enhanced surveillance to detect newly
emerging viruses is warranted.
PMID- 28518041
TI - Stockpiling Ventilators for Influenza Pandemics.
AB - In preparing for influenza pandemics, public health agencies stockpile critical
medical resources. Determining appropriate quantities and locations for such
resources can be challenging, given the considerable uncertainty in the timing
and severity of future pandemics. We introduce a method for optimizing stockpiles
of mechanical ventilators, which are critical for treating hospitalized influenza
patients in respiratory failure. As a case study, we consider the US state of
Texas during mild, moderate, and severe pandemics. Optimal allocations prioritize
local over central storage, even though the latter can be deployed adaptively, on
the basis of real-time needs. This prioritization stems from high geographic
correlations and the slightly lower treatment success assumed for centrally
stockpiled ventilators. We developed our model and analysis in collaboration with
academic researchers and a state public health agency and incorporated it into a
Web-based decision-support tool for pandemic preparedness and response.
PMID- 28518039
TI - Central Nervous System Brucellosis Granuloma and White Matter Disease in
Immunocompromised Patient.
AB - Brucellosis is a multisystem zoonotic disease. We report an unusual case of
neurobrucellosis with seizures in an immunocompromised patient in Saudi Arabia
who underwent renal transplantation. Magnetic resonance imaging of the brain
showed diffuse white matter lesions. Serum and cerebrospinal fluid were positive
for Brucella sp. Granuloma was detected in a brain biopsy specimen.
PMID- 28518042
TI - Autochthonous Case of Eosinophilic Meningitis Caused by Angiostrongylus
cantonensis, France, 2016.
AB - We report a case of a 54-year-old Moroccan woman living in France diagnosed with
eosinophilic meningitis caused by Angiostrongylus cantonensis. Diagnosis was
based on clinical symptoms and confirmed by testing of serum and cerebrospinal
fluid samples. Physicians should consider the risk for A. cantonensis infection
outside of endemic areas.
PMID- 28518043
TI - Congenital Malformations of Calves Infected with Shamonda Virus, Southern Japan.
AB - In 2015 and 2016, we observed 15 malformed calves that were exposed to
intrauterine infection with Shamonda virus, a Simbu serogroup orthobunyavirus, in
Japan. Characteristic manifestations were arthrogryposis and gross lesions in the
central nervous system. Our results indicate that this arbovirus should be
considered a teratogenic virus in ruminants.
PMID- 28518044
TI - PCR Detection of Mimivirus.
PMID- 28518045
TI - High Rates of Neutralizing Antibodies to Toscana and Sandfly Fever Sicilian
Viruses in Livestock, Kosovo.
AB - Toscana and sandfly fever Sicilian viruses (TOSV and SFSV, respectively), both
transmitted by sand flies, are prominent human pathogens in the Old World. Of
1,086 serum samples collected from cattle and sheep during 2013 in various
regions of Kosovo (Balkan Peninsula), 4.7% and 53.4% had neutralizing antibodies
against TOSV and SFSV, respectively.
PMID- 28518047
TI - Canadian Spine Society Abstracts 2017.
PMID- 28518046
TI - Epidemiologic Survey of Japanese Encephalitis Virus Infection, Tibet, China,
2015.
AB - We investigated Japanese encephalitis virus (JEV) prevalence in high-altitude
regions of Tibet, China, by using standard assays to test mosquitoes, pigs, and
humans. Results confirmed that JEV has spread to these areas. Disease prevention
and control strategies should be used along with surveillance to limit spread of
JEV in high-altitude regions of Tibet.
PMID- 28518048
TI - The potential adverse effects of haemolysis.
AB - Haemolysis occurs in many haematologic and non-haematologic diseases. Transfusion
of packed red blood cells (pRBCs) can result in intravascular haemolysis, in
which the RBCs are destroyed within the circulation, and extravascular
haemolysis, in which RBCs are phagocytosed in the monocyte-macrophage system.
This happens especially after RBCs have been stored under refrigerated conditions
for long periods. The clinical implications and the relative contribution of
intra- vs extra-vascular haemolysis are still a subject of debate. They have been
associated with adverse effects in animal models, but it remains to be determined
whether these may be involved in mediating adverse effects in humans.
PMID- 28518050
TI - Acetylcholinesterase provides new insights into red blood cell ageing in vivo and
in vitro.
AB - BACKGROUND: During its 120 days sojourn in the circulation, the red blood cell
(RBC) remodels its membrane. Acetylcholinesterase (AChE) is a
glycosylphosphatidylinositol (GPI)-linked enzyme that may serve as a marker for
membrane processes occurring this ageing-associated remodelling process.
MATERIALS AND METHODS: Expression and enzymatic activity of AChE were determined
on RBCs of various ages, as obtained by separation based on volume and density
(ageing in vivo), and on RBCs of various times of storage in blood bank
conditions (ageing in vitro), as well as on RBC-derived vesicles. RESULTS: During
ageing in vivo, the enzymatic activity of AChE decreases, but not the AChE
protein concentration. In contrast, neither AChE activity nor concentration show
a consistent, significant decrease during ageing in vitro. CD59, another GPI
linked protein that protects against complement-induced removal, also remains
constant during storage. The cellular content of the integral membrane protein
glycophorin A, however, decreases with storage time in the more dense RBC
fractions. The latter are enriched in echinocytes and other misshapen cells
during storage. DISCUSSION: Our findings suggest that, during RBC ageing, GPI
linked proteins and integral membrane proteins are differentially sorted. Also,
the vesicles that are generated in vitro show a fast and extensive loss of AChE
activity, but not of AChE expression. Thus, AChE characteristics may constitute
sensitive biomarkers of RBC ageing in vivo, and a source of information on the
structural and functional changes that GPI-linked proteins undergo during ageing
in vivo and in vitro. This information may help to understand RBC homeostasis and
the effects of transfusion, especially in immunologically compromised patients.
PMID- 28518052
TI - Italian consumption of plasma-derived factor VIII after the SIPPET study.
PMID- 28518051
TI - Red blood cells ageing markers: a multi-parametric analysis.
AB - BACKGROUND: Red blood cells collected in citrate-phosphate-dextrose can be stored
for up to 42 days at 4 degrees C in saline-adenine-glucose-mannitol additive
solution. During this controlled, but nevertheless artificial, ex vivo ageing,
red blood cells accumulate lesions that can be reversible or irreversible upon
transfusion. The aim of the present study is to follow several parameters
reflecting cell metabolism, antioxidant defences, morphology and membrane
dynamics during storage. MATERIALS AND METHODS: Five erythrocyte concentrates
were followed weekly during 71 days. Extracellular glucose and lactate
concentrations, total antioxidant power, as well as reduced and oxidised
intracellular glutathione levels were quantified. Microvesiculation, percentage
of haemolysis and haematologic parameters were also evaluated. Finally,
morphological changes and membrane fluctuations were recorded using label-free
digital holographic microscopy. RESULTS: The antioxidant power as well as the
intracellular glutathione concentration first increased, reaching maximal values
after one and two weeks, respectively. Irreversible morphological lesions
appeared during week 5, where discocytes began to transform into transient
echinocytes and finally spherocytes. At the same time, the microvesiculation and
haemolysis started to rise exponentially. After six weeks (expiration date),
intracellular glutathione was reduced by 25%, reflecting increasing oxidative
stress. The membrane fluctuations showed decreased amplitudes during shape
transition from discocytes to spherocytes. DISCUSSION: Various types of lesions
accumulated at different chemical and cellular levels during storage, which could
impact their in vivo recovery after transfusion. A marked effect was observed
after four weeks of storage, which corroborates recent clinical data. The
prolonged follow-up period allowed the capture of deep storage lesions.
Interestingly, and as previously described, the severity of the changes differed
among donors.
PMID- 28518053
TI - Effects of genetic variants in UGT1A1, SLCO1B3, ABCB1, ABCC2, ABCG2, ORM1 on
PK/PD of telmisartan in Chinese patients with mild to moderate essential
hypertension?.
AB - PURPOSE: This study aimed to understand the effects of single nucleotide
polymorphisms (SNPs) in UGT1A1, SLCO1B3, ABCB1, ABCC2, ABCG2, and ORM1 on the
pharmacokinetics (PK) (plasma concentration) and pharmacodynamics (PD) (blood
pressure) of telmisartan in Chinese patients. METHODS: 58 Han Chinese patients
(aged 45 - 72 years) with mild to moderate essential hypertension were included
and received 80 mg/day telmisartan for 4 weeks. The plasma concentration and
genetic variants were determined by LC/MS/MS and MALDI-TOF mass spectrometry,
respectively. Multivariable linear analysis was used to examine the relationships
between PK/PD and genetic variants. RESULTS: Females showed a significantly
higher AUClast than males (n = 22, 4,879.48 +/- 3,449.33 h*ng/mL vs. n
= 36, 2,715.59 +/- 2,223.77 h*ng/mL, p = 0.047). Amongst all genetic variants
investigated, the patients with UGT1A1 rs4124874 AA (n = 11, 1,730.51 +/-
1,325.79 h*ng/mL) had a significantly lower AUClast compared with
patients with UGT1A1 rs4124874 CC+AC (n = 19 + 28, 4,177.44 +/- 3,222.11 h*ng/mL
and 3,810.82 +/- 2,960.43 h*ng/mL, p = 0.027). None of the SNPs investigated was
associated with the PD responses to telmisartan. CONCLUSION: Variation of UGT1A1
(rs4124874) affects PK of telmisartan in Chinese patients, highlighting the value
of genetic testing in precision medicine as the telmisartan dose could be
adjusted based on UGT1A1 genetic variations.?.
PMID- 28518049
TI - Red blood cell storage time and transfusion: current practice, concerns and
future perspectives.
AB - Red blood cells (RBCs) units are the most requested transfusion product
worldwide. Indications for transfusion include symptomatic anaemia, acute sickle
cell crisis, and acute blood loss of more than 30% of the blood volume, with the
aim of restoring tissue oxygen delivery. However, stored RBCs from donors are not
a qualitative equal product, and, in many ways, this is a matter of concern in
the transfusion practice. Besides donor-to-donor variation, the storage time
influences the RBC unit at the qualitative level, as RBCs age in the storage bag
and are exposed to the so-called storage lesion. Several studies have shown that
the storage lesion leads to post-transfusion enhanced clearance, plasma
transferrin saturation, nitric oxide scavenging and/or immunomodulation with
potential unwanted transfusion-related clinical outcomes, such as acute lung
injury or higher mortality rate. While, to date, several studies have claimed the
risk or deleterious effects of "old" vs "young" RBC transfusion regimes, it is
still a matter of debate, and consideration should be taken of the clinical
context. Transfusion-dependent patients may benefit from transfusion with "young"
RBC units, as it assures longer inter-transfusion periods, while transfusion with
"old" RBC units is not itself harmful. Unbiased Omics approaches are being
applied to the characterisation of RBC through storage, to better understand the
(patho)physiological role of microparticles (MPs) that are found naturally, and
also on stored RBC units. Perhaps RBC storage time is not an accurate surrogate
for RBC quality and there is a need to establish which parameters do indeed
reflect optimal efficacy and safety. A better Omics characterisation of
components of "young" and "old" RBC units, including MPs, donor and recipient,
might lead to the development of new therapies, including the use of engineered
RBCs or MPs as cell-based drug delivering tools, or cost-effective personalised
transfusion strategies.
PMID- 28518054
TI - Comparison of three estimators for determining cyclosporine dosing in infants
after liver transplantation?.
AB - OBJECTIVE: To compare and analyze how allometrically- and linearly-scaled daily
doses of cyclosporine could affect the therapeutic drug monitoring concentrations
when applied to 8 infants with liver transplants. MATERIALS AND METHODS: Eight
infants who underwent liver transplantations were put on twice-daily oral
cyclosporine immunosuppressive regimens. After starting therapy, the adjustments
of individual daily doses were determined by using therapeutic monitoring of
plasma cyclosporine levels by measuring trough concentrations (C0) and
concentrations at 2 hours after drug administration (C2). These doses
were analyzed and compared with the hypothetical doses estimated by allometric
and linear scaling in order to compare which of the two methods would yield
closer estimates to the actual doses applied. RESULTS: The median therapeutic
drug monitoring (TDM)-based dose (n = 53) was 70.00 mg (10.9 mg/kg/day) (5.00 -
190.00 mg), whereas the median allometric (n = 53) and linear (n = 53) doses were
65.21 mg (10.11 mg/kg/day) (57.17 - 79.25 mg) and 35.63 mg (5.52 mg/kg/day)
(29.89 - 46.20 mg), respectively. The median allometric dose was significantly
different than the median linear dose (p < 0.0001), whereas there was no
statistical difference between the median TDM-based dose and median allometric
dose (p = 0.72). CONCLUSIONS: The allometric approach, when used to estimate
cyclosporine doses in this cohort of liver transplant infants, yielded closer
estimates to actually applied daily doses in comparison to linear scaling.
Allometric scaling could be employed in calculating starting doses for drugs that
lack specific dosing recommendations for infants, in order to achieve therapeutic
levels faster, lowering the need for constant monitoring and dose adjustment.?.
PMID- 28518058
TI - Prediction of NSCLC recurrence from microarray data with GEP.
AB - Lung cancer is one of the deadliest diseases in the world. Non-small cell lung
cancer (NSCLC) is the most common and dangerous type of lung cancer. Despite the
fact that NSCLC is preventable and curable for some cases if diagnosed at early
stages, the vast majority of patients are diagnosed very late. Furthermore, NSCLC
usually recurs sometime after treatment. Therefore, it is of paramount importance
to predict NSCLC recurrence, so that specific and suitable treatments can be
sought. Nonetheless, conventional methods of predicting cancer recurrence rely
solely on histopathology data and predictions are not reliable in many cases. The
microarray gene expression (GE) technology provides a promising and reliable way
to predict NSCLC recurrence by analysing the GE of sample cells. This study
proposes a new model from GE programming to use microarray datasets for NSCLC
recurrence prediction. To this end, the authors also propose a hybrid method to
rank and select relevant prognostic genes that are related to NSCLC recurrence
prediction. The proposed model was evaluated on real NSCLC microarray datasets
and compared with other representational models. The results demonstrated the
effectiveness of the proposed model.
PMID- 28518056
TI - Functionally diverse human T cells recognize non-microbial antigens presented by
MR1.
AB - MHC class I-related molecule MR1 presents riboflavin- and folate-related
metabolites to mucosal-associated invariant T cells, but it is unknown whether
MR1 can present alternative antigens to other T cell lineages. In healthy
individuals we identified MR1-restricted T cells (named MR1T cells) displaying
diverse TCRs and reacting to MR1-expressing cells in the absence of microbial
ligands. Analysis of MR1T cell clones revealed specificity for distinct cell
derived antigens and alternative transcriptional strategies for metabolic
programming, cell cycle control and functional polarization following antigen
stimulation. Phenotypic and functional characterization of MR1T cell clones
showed multiple chemokine receptor expression profiles and secretion of diverse
effector molecules, suggesting functional heterogeneity. Accordingly, MR1T cells
exhibited distinct T helper-like capacities upon MR1-dependent recognition of
target cells expressing physiological levels of surface MR1. These data extend
the role of MR1 beyond microbial antigen presentation and indicate MR1T cells are
a normal part of the human T cell repertoire.
PMID- 28518057
TI - On the mechanistic nature of epistasis in a canonical cis-regulatory element.
AB - Understanding the relation between genotype and phenotype remains a major
challenge. The difficulty of predicting individual mutation effects, and
particularly the interactions between them, has prevented the development of a
comprehensive theory that links genotypic changes to their phenotypic effects. We
show that a general thermodynamic framework for gene regulation, based on a
biophysical understanding of protein-DNA binding, accurately predicts the sign of
epistasis in a canonical cis-regulatory element consisting of overlapping RNA
polymerase and repressor binding sites. Sign and magnitude of individual mutation
effects are sufficient to predict the sign of epistasis and its environmental
dependence. Thus, the thermodynamic model offers the correct null prediction for
epistasis between mutations across DNA-binding sites. Our results indicate that a
predictive theory for the effects of cis-regulatory mutations is possible from
first principles, as long as the essential molecular mechanisms and the
constraints these impose on a biological system are accounted for.
PMID- 28518059
TI - Recent omics technologies and their emerging applications for personalised
medicine.
AB - A major objective of 'omics' technologies is to understand genetic causality of
complex traits of human diseases. High-throughput omics technologies and their
application to medicine open up remarkable opportunities for realising optimised
medical treatment for individuals. Because many major breakthrough and
discoveries in this field have been driven by the development of new omics
technologies, in this review, the authors aim to provide an in-depth description
of their underlying principles as a foundation of developing another new omics
technology, and to introduce their emerging applications for personalised
medicine. The systems biology approach is then introduced as a future direction
towards actionable personalised medicine.
PMID- 28518055
TI - A positive feedback loop linking enhanced mGluR function and basal calcium in
spinocerebellar ataxia type 2.
AB - Metabotropic glutamate receptor 1 (mGluR1) function in Purkinje neurons (PNs) is
essential for cerebellar development and for motor learning and altered mGluR1
signaling causes ataxia. Downstream of mGluR1, dysregulation of calcium
homeostasis has been hypothesized as a key pathological event in genetic forms of
ataxia but the underlying mechanisms remain unclear. We find in a spinocerebellar
ataxia type 2 (SCA2) mouse model that calcium homeostasis in PNs is disturbed
across a broad range of physiological conditions. At parallel fiber synapses,
mGluR1-mediated excitatory postsynaptic currents (EPSCs) and associated calcium
transients are increased and prolonged in SCA2 PNs. In SCA2 PNs, enhanced mGluR1
function is prevented by buffering [Ca2+] at normal resting levels while in
wildtype PNs mGluR1 EPSCs are enhanced by elevated [Ca2+]. These findings
demonstrate a deleterious positive feedback loop involving elevated intracellular
calcium and enhanced mGluR1 function, a mechanism likely to contribute to PN
dysfunction and loss in SCA2.
PMID- 28518060
TI - Analysis of healthy and tumour DNA methylation distributions in kidney-renal
clear-cell-carcinoma using Kullback-Leibler and Jensen-Shannon distance measures.
AB - DNA methylation is an epigenetic phenomenon in which methyl groups get bonded to
the cytosines of the DNA molecule altering the expression of the associated
genes. Cancer is linked with hypo or hyper-methylation of specific genes as well
as global changes in DNA methylation. In this study, the authors study the
probability density function distribution of DNA methylation in various
significant genes and across the genome in healthy and tumour samples. They
propose a unique 'average healthy methylation distribution' based on the
methylation values of several healthy samples. They then obtain the Kullback
Leibler and Jensen-Shannon distances between methylation distributions of the
healthy and tumour samples and the average healthy methylation distribution. The
distance measures of the healthy and tumour samples from the average healthy
methylation distribution are compared and the differences in the distances are
analysed as possible parameters for cancer. A classifier trained on these values
was found to provide high values of sensitivity and specificity. They consider
this to be a computationally efficient approach to predict tumour samples based
on DNA methylation data. This technique can also be improvised to consider other
differentially methylated genes significant in cancer or other epigenetic
diseases.
PMID- 28518061
TI - Graft Quality and Prediction of Outcome After Liver Transplantation.
PMID- 28518062
TI - Retrograde Flushing of Living Donor Renal Allografts via the Renal Vein: A
Simple, Effective Technique.
AB - BACKGROUND: Prograde flushing (PF) of living donor renal allografts with
preservation solution via the renal artery or arteries is standard practice. PF
may be difficult and potentially injurious to the donor kidney, especially in
grafts with small or multiple arteries. In this report, we present our experience
with retrograde flushing (RF) of 7 living donor kidneys via the renal vein.
METHODS: Retrospective review of 7 consecutive living donor renal transplants
performed using the RF technique was performed. The 7 preceding living donor
renal transplants performed using the standard arterial PF technique served as a
control group. RESULTS: All 7 recipients of RF kidneys experienced immediate
graft function. At postoperative days 3 and 30, there was no difference in
estimated glomerular filtration rate between the RF study group and PF controls.
CONCLUSIONS: The RF technique is simple and safe, with results equivalent to the
PF technique. The RF technique may be especially useful after recovering kidneys
with small and/or multiple arteries.
PMID- 28518063
TI - Visualizing Visual Adaptation.
AB - Many techniques have been developed to visualize how an image would appear to an
individual with a different visual sensitivity: e.g., because of optical or age
differences, or a color deficiency or disease. This protocol describes a
technique for incorporating sensory adaptation into the simulations. The protocol
is illustrated with the example of color vision, but is generally applicable to
any form of visual adaptation. The protocol uses a simple model of human color
vision based on standard and plausible assumptions about the retinal and cortical
mechanisms encoding color and how these adjust their sensitivity to both the
average color and range of color in the prevailing stimulus. The gains of the
mechanisms are adapted so that their mean response under one context is equated
for a different context. The simulations help reveal the theoretical limits of
adaptation and generate "adapted images" that are optimally matched to a specific
environment or observer. They also provide a common metric for exploring the
effects of adaptation within different observers or different environments.
Characterizing visual perception and performance with these images provides a
novel tool for studying the functions and consequences of long-term adaptation in
vision or other sensory systems.
PMID- 28518064
TI - An Experimental and Finite Element Protocol to Investigate the Transport of
Neutral and Charged Solutes across Articular Cartilage.
AB - Osteoarthritis (OA) is a debilitating disease that is associated with
degeneration of articular cartilage and subchondral bone. Degeneration of
articular cartilage impairs its load-bearing function substantially as it
experiences tremendous chemical degradation, i.e. proteoglycan loss and collagen
fibril disruption. One promising way to investigate chemical damage mechanisms
during OA is to expose the cartilage specimens to an external solute and monitor
the diffusion of the molecules. The degree of cartilage damage (i.e.
concentration and configuration of essential macromolecules) is associated with
collisional energy loss of external solutes while moving across articular
cartilage creates different diffusion characteristics compared to healthy
cartilage. In this study, we introduce a protocol, which consists of several
steps and is based on previously developed experimental micro-Computed Tomography
(micro-CT) and finite element modeling. The transport of charged and uncharged
iodinated molecules is first recorded using micro-CT, which is followed by
applying biphasic-solute and multiphasic finite element models to obtain
diffusion coefficients and fixed charge densities across cartilage zones.
PMID- 28518065
TI - Transient Middle Cerebral Artery Occlusion Model of Neonatal Stroke in P10 Rats.
AB - A number of animal models have been used to study hypoxic-ischemic injury,
traumatic injury, global hypoxia, or permanent ischemia in both the immature and
mature brain. Stroke occurs commonly in the perinatal period in humans, and
transient ischemia-reperfusion is the most common form of stroke in neonates. The
reperfusion phase is a critical component of injury progression, which occurs
over a period of days to weeks, and of the endogenous response to injury. This
postnatal day 10 (p10) rat model of transient middle cerebral artery occlusion
(tMCAO) creates a unilateral, non-hemorrhagic focal ischemia-reperfusion injury
that can be utilized to study the mechanisms of focal injury and repair in the
full-term-equivalent brain. The injury pattern that is produced by tMCAO is
consistent and highly reproducible and can be confirmed with MRI or histological
analyses. The severity of injury can be manipulated through changes in occlusion
time and other methods that will be discussed.
PMID- 28518066
TI - Scaled Anatomical Model Creation of Biomedical Tomographic Imaging Data and
Associated Labels for Subsequent Sub-surface Laser Engraving (SSLE) of Glass
Crystals.
AB - Biomedical imaging modalities like computed tomography (CT) and magnetic
resonance (MR) provide excellent platforms for collecting three-dimensional data
sets of patient or specimen anatomy in clinical or preclinical settings. However,
the use of a virtual, on-screen display limits the ability of these tomographic
images to fully convey the anatomical information embedded within. One solution
is to interface a biomedical imaging data set with 3D printing technology to
generate a physical replica. Here we detail a complementary method to visualize
tomographic imaging data with a hand-held model: Sub Surface Laser Engraving
(SSLE) of crystal glass. SSLE offers several unique benefits including: the
facile ability to include anatomical labels, as well as a scale bar; streamlined
multipart assembly of complex structures in one medium; high resolution in the X,
Y, and Z planes; and semi-transparent shells for visualization of internal
anatomical substructures. Here we demonstrate the process of SSLE with CT data
sets derived from pre-clinical and clinical sources. This protocol will serve as
a powerful and inexpensive new tool with which to visualize complex anatomical
structures for scientists and students in a number of educational and research
settings.
PMID- 28518067
TI - Remote Sensing Evaluation of Two-spotted Spider Mite Damage on Greenhouse Cotton.
AB - The objective of this study was to evaluate a ground-based multispectral optical
sensor as a remote sensing tool to assess foliar damage caused by the two-spotted
spider mite (TSSM), Tetranychus urticae Koch, on greenhouse grown cotton. TSSM is
a polyphagous pest which occurs on a variety of field and horticultural crops. It
often becomes an early season pest of cotton in damaging proportions as opposed
to being a late season innocuous pest in the mid-southern United States.
Evaluation of acaricides is important for maintaining the efficacy of and
preventing resistance to the currently available arsenal of chemicals and newly
developed control agents. Enumeration of spider mites for efficacy evaluations is
laborious and time consuming. Therefore, subjective visual damage rating is
commonly used to assess density of spider mites. The NDVI (Normalized Difference
Vegetation Index) is the most widely used statistic to describe the spectral
reflectance characteristics of vegetation canopy to assess plant stress and
health consequent to spider mite infestations. Results demonstrated that a
multispectral optical sensor is an effective tool in distinguishing varying
levels of infestation caused by T. urticae on early season cotton. This remote
sensing technique may be used in lieu of a visual rating to evaluate insecticide
treatments.
PMID- 28518068
TI - 3D Magnetic Stem Cell Aggregation and Bioreactor Maturation for Cartilage
Regeneration.
AB - Cartilage engineering remains a challenge due to the difficulties in creating an
in vitro functional implant similar to the native tissue. An approach recently
explored for the development of autologous replacements involves the
differentiation of stem cells into chondrocytes. To initiate this chondrogenesis,
a degree of compaction of the stem cells is required; hence, we demonstrated the
feasibility of magnetically condensing cells, both within thick scaffolds and
scaffold-free, using miniaturized magnetic field sources as cell attractors. This
magnetic approach was also used to guide aggregate fusion and to build scaffold
free, organized, three-dimensional (3D) tissues several millimeters in size. In
addition to having an enhanced size, the tissue formed by magnetic-driven fusion
presented a significant increase in the expression of collagen II, and a similar
trend was observed for aggrecan expression. As the native cartilage was subjected
to forces that influenced its 3D structure, dynamic maturation was also
performed. A bioreactor that provides mechanical stimuli was used to culture the
magnetically seeded scaffolds over a 21-day period. Bioreactor maturation largely
improved chondrogenesis into the cellularized scaffolds; the extracellular matrix
obtained under these conditions was rich in collagen II and aggrecan. This work
outlines the innovative potential of magnetic condensation of labeled stem cells
and dynamic maturation in a bioreactor for improved chondrogenic differentiation,
both scaffold-free and within polysaccharide scaffolds.
PMID- 28518069
TI - Modification and Functionalization of the Guanidine Group by Tailor-made
Precursors.
AB - The guanidine group is one of the most important pharmacophoric groups in
medicinal chemistry. The only amino acid carrying a guanidine group is arginine.
In this article, an easy method for the modification of the guanidine group in
peptidic ligands is provided, with an example of RGD-binding integrin ligands. It
was recently demonstrated that the distinct modification of the guanidine group
in these ligands allows for the selective modulation of the subtype (e.g.,
between the subtypes alphav and alpha5). Moreover, a formerly unknown strategy
for the functionalization via the guanidine group was demonstrated, and the
synthetic approach is reviewed in this document. The modifications described here
involve terminally (Nomega) alkylated and acetylated guanidine groups. For the
synthesis, tailor-made precursor molecules are synthesized, which are then
subjected to a reaction with an orthogonally deprotected amine to transfer the
pre-modified guanidine group. For the synthesis of alkylated guanidines,
precursors based on N,N'-Di-Boc-1H-pyrazole-1-carboxamidine are used to
synthesize acylated compounds, the precursor of choice being a correspondingly
acylated derivative of N-Boc-S-methylisothiourea, which can be obtained in one-
and two-step reactions.
PMID- 28518070
TI - Sample Preparation for Mass Cytometry Analysis.
AB - Mass cytometry utilizes antibodies conjugated with heavy metal labels, an
approach that has greatly increased the number of parameters and opportunities
for deep analysis well beyond what is possible with conventional fluorescence
based flow cytometry. As with any new technology, there are critical steps that
help ensure the reliable generation of high-quality data. Presented here is an
optimized protocol that incorporates multiple techniques for the processing of
cell samples for mass cytometry analysis. The methods described here will help
the user avoid common pitfalls and achieve consistent results by minimizing
variability, which can lead to inaccurate data. To inform experimental design,
the rationale behind optional or alternative steps in the protocol and their
efficacy in uncovering new findings in the biology of the system being
investigated is covered. Lastly, representative data is presented to illustrate
expected results from the techniques presented here.
PMID- 28518071
TI - Nerve-sparing Mid-urethral Obstruction (NeMO) in Female Small Rodents.
AB - Partial bladder outlet obstruction (pBOO) has a high prevalence, causes
significant patient burden, and immense health care costs. The most common animal
model to investigate bladder remodeling in pBOO are female rodents undergoing
partial obstruction at the proximal urethra. Variability in the degree of
obstruction and animal mortality are major concerns with proximal obstruction.
Furthermore, dissecting around the proximal urethra and bladder neck jeopardizes
bladder innervation. We developed a nerve-sparing mid-urethral obstruction (NeMO)
model for pBOO avoiding the disadvantages of the traditional model. We approached
the urethra just inferior to the pubic symphysis, which obviated the need for
laparotomy as well as for dissection in this area; also, the striated urethral
sphincter remained untouched. We performed NeMO in female Sprague-Dawley rats (12
obstructions, 6 sham animals) as well as in female C57/bl6 mice (20 obstructions,
18 sham animals). After two weeks, we evaluated bladder function, bladder mass,
and body mass. We had no mortalities among obstructed- or sham-operated female
rats; as described for the traditional proximal pBOO-method, we tied the suture
around the proximal urethra and a temporarily placed 0.9 mm metal rod. NeMO
induced an 85% increase in bladder mass after two weeks, average residual urine
volume was 0.4 mL in partially obstructed rats while only 0.03 mL in sham
animals. In mice, we tested 3 sizes of cannulas that we placed along the urethra
when tying the suture. We found that using a 27-gauge cannula resulted in over
50% animal mortality; placing the 25-gauge cannula did not yield the desired
response in increasing bladder mass; utilizing a 26-gauge cannula yielded
favorable results with minimal animal mortality (1/8) yet a significant 2-fold
increase in bladder mass.
PMID- 28518072
TI - In Vivo Investigation of Antimicrobial Blue Light Therapy for Multidrug-resistant
Acinetobacter baumannii Burn Infections Using Bioluminescence Imaging.
AB - Burn infections continue to be an important cause of morbidity and mortality. The
increasing emergence of multidrug-resistant (MDR) bacteria has led to the
frequent failure of traditional antibiotic treatments. Alternative therapeutics
are urgently needed to tackle MDR bacteria. An innovative non-antibiotic
approach, antimicrobial blue light (aBL), has shown promising effectiveness
against MDR infections. The mechanism of action of aBL is not yet well
understood. It is commonly hypothesized that naturally occurring endogenous
photosensitizing chromophores in bacteria (e.g., iron-free porphyrins, flavins,
etc.) are excited by aBL, which in turn produces cytotoxic reactive oxygen
species (ROS) through a photochemical process. Unlike another light-based
antimicrobial approach, antimicrobial photodynamic therapy (aPDT), aBL therapy
does not require the involvement of an exogenous photosensitizer. All it needs to
take effect is the irradiation of blue light; therefore, it is simple and
inexpensive. The aBL receptors are the endogenous cellular photosensitizers in
bacteria, rather than the DNA. Thus, aBL is believed to be much less genotoxic to
host cells than ultraviolet-C (UVC) irradiation, which directly causes DNA damage
in host cells. In this paper, we present a protocol to assess the effectiveness
of aBL therapy for MDR Acinetobacter baumannii infections in a mouse model of
burn injury. By using an engineered bioluminescent strain, we were able to
noninvasively monitor the extent of infection in real time in living animals.
This technique is also an effective tool for monitoring the spatial distribution
of infections in animals.
PMID- 28518073
TI - Extraction and Characterization of Surfactants from Atmospheric Aerosols.
AB - Surface-active compounds, or surfactants, present in atmospheric aerosols are
expected to play important roles in the formation of liquid water clouds in the
Earth's atmosphere, a central process in meteorology, hydrology, and for the
climate system. But because specific extraction and characterization of these
compounds have been lacking for decades, very little is known on their identity,
properties, mode of action and origins, thus preventing the full understanding of
cloud formation and its potential links with the Earth's ecosystems. In this
paper we present recently developed methods for 1) the targeted extraction of all
the surfactants from atmospheric aerosol samples and for the determination of 2)
their absolute concentrations in the aerosol phase and 3) their static surface
tension curves in water, including their Critical Micelle Concentration (CMC).
These methods have been validated with 9 references surfactants, including
anionic, cationic and non-ionic ones. Examples of results are presented for
surfactants found in fine aerosol particles (diameter <1 MUm) collected at a
coastal site in Croatia and suggestions for future improvements and other
characterizations than those presented are discussed.
PMID- 28518075
TI - Leveraging CyVerse Resources for De Novo Comparative Transcriptomics of
Underserved (Non-model) Organisms.
AB - This workflow allows novice researchers to leverage advanced computational
resources such as cloud computing to carry out pairwise comparative
transcriptomics. It also serves as a primer for biologists to develop data
scientist computational skills, e.g. executing bash commands, visualization and
management of large data sets. All command line code and further explanations of
each command or step can be found on the wiki
(https://wiki.cyverse.org/wiki/x/dgGtAQ). The Discovery Environment and
Atmosphere platforms are connected together through the CyVerse Data Store. As
such, once the initial raw sequencing data has been uploaded there is no more
need to transfer large data files over an Internet connection, minimizing the
amount of time needed to conduct analyses. This protocol is designed to analyze
only two experimental treatments or conditions. Differential gene expression
analysis is conducted through pairwise comparisons, and will not be suitable to
test multiple factors. This workflow is also designed to be manual rather than
automated. Each step must be executed and investigated by the user, yielding a
better understanding of data and analytical outputs, and therefore better results
for the user. Once complete, this protocol will yield de novo assembled
transcriptome(s) for underserved (non-model) organisms without the need to map to
previously assembled reference genomes (which are usually not available in
underserved organism). These de novo transcriptomes are further used in pairwise
differential gene expression analysis to investigate genes differing between two
experimental conditions. Differentially expressed genes are then functionally
annotated to understand the genetic response organisms have to experimental
conditions. In total, the data derived from this protocol is used to test
hypotheses about biological responses of underserved organisms.
PMID- 28518074
TI - Eliciting and Analyzing Male Mouse Ultrasonic Vocalization (USV) Songs.
AB - Mice produce ultrasonic vocalizations (USVs) in a variety of social contexts
throughout development and adulthood. These USVs are used for mother-pup
retrieval1, juvenile interactions2, opposite and same sex interactions3,4,5, and
territorial interactions6. For decades, the USVs have been used by investigators
as proxies to study neuropsychiatric and developmental or behavioral
disorders7,8,9, and more recently to understand mechanisms and evolution of vocal
communication among vertebrates10. Within the sexual interactions, adult male
mice produce USV songs, which have some features similar to courtship songs of
songbirds11. The use of such multisyllabic repertoires can increase potential
flexibility and information they carry, as they can be varied in how elements are
organized and recombined, namely syntax. In this protocol a reliable method to
elicit USV songs from male mice in various social contexts, such as exposure to
fresh female urine, anesthetized animals, and estrus females is described. This
includes conditions to induce a large amount of syllables from the mice. We
reduce recording of ambient noises with inexpensive sound chambers, and present a
quantification method to automatically detect, classify and analyze the USVs. The
latter includes evaluation of call-rate, vocal repertoire, acoustic parameters,
and syntax. Various approaches and insight on using playbacks to study an
animal's preference for specific song types are described. These methods were
used to describe acoustic and syntax changes across different contexts in male
mice, and song preferences in female mice.
PMID- 28518076
TI - Facile Preparation of Ultrafine Aluminum Hydroxide Particles with or without
Mesoporous MCM-41 in Ambient Environments.
AB - An aqueous suspension of nanogibbsite was synthesized via the titration of
aluminum aqua acid [Al(H2O)6]3+ with L-arginine to pH 4.6. Since the hydrolysis
of aqueous aluminum salts is known to produce a wide array of products with a
wide range of size distributions, a variety of state-of-the-art instruments
(i.e., 27Al/1H NMR, FTIR, ICP-OES, TEM-EDX, XPS, XRD, and BET) were used to
characterize the synthesis products and identification of byproducts. The
product, which was comprised of nanoparticles (10-30 nm), was isolated using gel
permeation chromatography (GPC) column technique. Fourier transform infrared
(FTIR) spectroscopy and powder X-ray diffraction (PXRD) identified the purified
material as the gibbsite polymorph of aluminum hydroxide. The addition of
inorganic salts (e.g., NaCl) induced electrostatic destabilization of the
suspension, thereby agglomerating the nanoparticles to yield Al(OH)3 precipitate
with large particle sizes. By utilizing the novel synthetic method described
here, Al(OH)3 was partially loaded inside the highly ordered mesoporous framework
of MCM-41, with average pore dimensions of 2.7 nm, producing an aluminosilicate
material with both octahedral and tetrahedral Al (Oh/Td = 1.4). The total Al
content, measured using energy-dispersive X-ray spectrometry (EDX), was 11% w/w
with a Si/Al molar ratio of 2.9. A comparison of bulk EDX with surface X-ray
photoelectron spectroscopy (XPS) elemental analysis provided insight into the
distribution of Al within the aluminosilicate material. Furthermore, a higher
ratio of Si/Al was observed on the external surface (3.6) as compared to the bulk
(2.9). Approximations of O/Al ratios suggest a higher concentration of Al(O)3 and
Al(O)4 groups near the core and external surface, respectively. The newly
developed synthesis of Al-MCM-41 yields a relatively high Al content while
maintaining the integrity of the ordered silica framework and can be used for
applications where hydrated or anhydrous Al2O3 nanoparticles are advantageous.
PMID- 28518077
TI - Inkjet-printed Polyvinyl Alcohol Multilayers.
AB - Inkjet printing is a modern method for polymer processing, and in this work, we
demonstrate that this technology is capable of producing polyvinyl alcohol (PVOH)
multilayer structures. A polyvinyl alcohol aqueous solution was formulated. The
intrinsic properties of the ink, such as surface tension, viscosity, pH, and time
stability, were investigated. The PVOH-based ink was a neutral solution (pH 6.7)
with a surface tension of 39.3 mN/m and a viscosity of 7.5 cP. The ink displayed
pseudoplastic (non-Newtonian shear thinning) behavior at low shear rates, and
overall, it demonstrated good time stability. The wettability of the ink on
different substrates was investigated, and glass was identified as the most
suitable substrate in this particular case. A proprietary 3D inkjet printer was
employed to manufacture polymer multilayer structures. The morphology, surface
profile, and thickness uniformity of inkjet-printed multilayers were evaluated
via optical microscopy.
PMID- 28518078
TI - Non-invasive In Vivo Fluorescence Optical Imaging of Inflammatory MMP Activity
Using an Activatable Fluorescent Imaging Agent.
AB - This paper describes a non-invasive method for imaging matrix metalloproteinases
(MMP)-activity by an activatable fluorescent probe, via in vivo fluorescence
optical imaging (OI), in two different mouse models of inflammation: a rheumatoid
arthritis (RA) and a contact hypersensitivity reaction (CHR) model. Light with a
wavelength in the near infrared (NIR) window (650 - 950 nm) allows a deeper
tissue penetration and minimal signal absorption compared to wavelengths below
650 nm. The major advantages using fluorescence OI is that it is cheap, fast and
easy to implement in different animal models. Activatable fluorescent probes are
optically silent in their inactivated states, but become highly fluorescent when
activated by a protease. Activated MMPs lead to tissue destruction and play an
important role for disease progression in delayed-type hypersensitivity reactions
(DTHRs) such as RA and CHR. Furthermore, MMPs are the key proteases for cartilage
and bone degradation and are induced by macrophages, fibroblasts and chondrocytes
in response to pro-inflammatory cytokines. Here we use a probe that is activated
by the key MMPs like MMP-2, -3, -9 and -13 and describe an imaging protocol for
near infrared fluorescence OI of MMP activity in RA and control mice 6 days after
disease induction as well as in mice with acute (1x challenge) and chronic (5x
challenge) CHR on the right ear compared to healthy ears.
PMID- 28518080
TI - Rearing Ixodes scapularis, the Black-legged Tick: Feeding Immature Stages on
Mice.
AB - Ixodes scapularis, the vector of Lyme disease, is one of the most important
disease vectors in the eastern and Midwestern United States. This species is a
three host tick that requires a blood meal from a vertebrate host for each
development stage, and the adult females require a blood meal for reproduction.
Larval ticks attach to their host for 3 - 5 days for feeding and drop off the
host when fully engorged. This dependency on several different hosts and the
lengthy attachment time for engorgement complicates tick rearing in the
laboratory setting. However, to understand tick biology and tick-pathogen
interactions, the production of healthy, laboratory-reared ticks is essential.
Here, we demonstrate a simple, cost-effective protocol for immature tick feeding
on mice. We modified the existing protocols for decreased stress on mice and
increased tick feeding success and survival by using disposable cages without
mesh bottoms to avoid contact of ticks with water contaminated with mice urine
and feces.
PMID- 28518079
TI - A Method for Quantifying Upper Limb Performance in Daily Life Using
Accelerometers.
AB - A key reason for referral to rehabilitation services after stroke and other
neurological conditions is to improve one's ability to function in daily life. It
has become important to measure a person's activities in daily life, and not just
measure their capacity for activity in the structured environment of a clinic or
laboratory. A wearable sensor that is now enabling measurement of daily movement
is the accelerometer. Accelerometers are commercially-available devices
resembling large wrist watches that can be worn throughout the day. Data from
accelerometers can quantify how the limbs are engaged to perform activities in
peoples' homes and communities. This report describes a methodology to collect
accelerometry data and turn it into clinically-relevant information. First, data
are collected by having the participant wear two accelerometers (one on each
wrist) for 24 h or longer. The accelerometry data are then downloaded and
processed to produce four different variables that describe key aspects of upper
limb activity in daily life: hours of use, use ratio, magnitude ratio, and the
bilateral magnitude. Density plots can be constructed that visually represent the
data from the 24 h wearing period. The variables and their resultant density
plots are highly consistent in neurologically-intact, community-dwelling adults.
This striking consistency makes them a useful tool for determining if upper limb
daily performance is different from normal. This methodology is appropriate for
research studies investigating upper limb dysfunction and interventions designed
to improve upper limb performance in daily life in people with stroke and other
patient populations. Because of its relative simplicity, it may not be long
before it is also incorporated in clinical neurorehabilitation practice.
PMID- 28518081
TI - Determining Glucose Metabolism Kinetics Using 18F-FDG Micro-PET/CT.
AB - This paper describes the use of 18F-FDG and micro-PET/CT imaging to determine in
vivo glucose metabolism kinetics in mice (and is transferable to rats). Impaired
uptake and metabolism of glucose in multiple organ systems due to insulin
resistance is a hallmark of type 2 diabetes. The ability of this technique to
extract an image-derived input function from the vena cava using an iterative
deconvolution method eliminates the requirement of the collection of arterial
blood samples. Fitting of tissue and vena cava time activity curves to a two
tissue, three compartment model permits the estimation of kinetic micro
parameters related to the 18F-FDG uptake from the plasma to the intracellular
space, the rate of transport from intracellular space to plasma and the rate of
18F-FDG phosphorylation. This methodology allows for multiple measures of glucose
uptake and metabolism kinetics in the context of longitudinal studies and also
provides insights into the efficacy of therapeutic interventions.
PMID- 28518082
TI - Maturation of Human Stem Cell-derived Cardiomyocytes in Biowires Using Electrical
Stimulation.
AB - Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have been a
promising cell source and have thus encouraged the investigation of their
potential applications in cardiac research, including drug discovery, disease
modeling, tissue engineering, and regenerative medicine. However, cells produced
by existing protocols display a range of immaturity compared with native adult
ventricular cardiomyocytes. Many efforts have been made to mature hPSC-CMs, with
only moderate maturation attained thus far. Therefore, an engineered system,
called biowire, has been devised by providing both physical and electrical cues
to lead hPSC-CMs to a more mature state in vitro. The system uses a
microfabricated platform to seed hPSC-CMs in collagen type I gel along a rigid
template suture to assemble into aligned cardiac tissue (biowire), which is
subjected to electrical field stimulation with a progressively increasing
frequency. Compared to nonstimulated controls, stimulated biowired cardiomyocytes
exhibit an enhanced degree of structural and electrophysiological maturation.
Such changes are dependent upon the stimulation rate. This manuscript describes
in detail the design and creation of biowires.
PMID- 28518083
TI - Bronchoalveolar Lavage of Murine Lungs to Analyze Inflammatory Cell Infiltration.
AB - Bronchoalveolar Lavage (BAL) is an experimental procedure that is used to examine
the cellular and acellular content of the lung lumen ex vivo to gain insight into
an ongoing disease state. Here, a simple and efficient method is described to
perform BAL on murine lungs without the need of special tools or equipment. BAL
fluid is isolated by inserting a catheter in the trachea of terminally
anesthetized mice, through which a saline solution is instilled into the
bronchioles. The instilled fluid is gently retracted to maximize BAL fluid
retrieval and to minimize shearing forces. This technique allows the viability,
function, and structure of cells within the airways and BAL fluid to be
preserved. Numerous techniques may be applied to gain further understanding of
the disease state of the lung. Here, a commonly used technique for the
identification and enumeration of different types of immune cells is described,
where flow cytometry is combined with a select panel of fluorescently labeled
cell surface-specific markers. The BAL procedure presented here can also be used
to analyze infectious agents, fluid constituents, or inhaled particles within
murine lungs.
PMID- 28518084
TI - Subcutaneous Trigeminal Nerve Field Stimulation for Refractory Facial Pain.
AB - Chronic or neuropathic trigeminal facial pain can be challenging to treat.
Neurosurgical procedures should be applied when conservative treatment fails.
Neuromodulation techniques for chronic facial pain include deep brain stimulation
and motor cortex stimulation, which are complex to perform. Subcutaneous nerve
field stimulation is certified for chronic back pain and is the least invasive
form of neuromodulation. We applied this technique to treat chronic and
neuropathic trigeminal pain as an individual therapy concept. First, trial
stimulation is performed. Subcutaneous leads are placed in the painful trigeminal
dermatome under local anesthesia. The leads are connected to an external
neurostimulator that applies constant stimulation. Patients undergo a 12 day
outpatient trial to assess the effect of the stimulation. Electrodes are removed
after the trial. If the patient reports pain reduction of at least 50% in
intensity and/or attack frequency, a reduction in medication or increase in
quality of life, permanent implantation is scheduled. New electrodes are
implanted under general anesthesia and are subcutaneously tunneled to an
infraclavicular internal pulse generator. Patients are able to turn stimulation
on and off and to increase or decrease the stimulation amplitude as needed. This
technique represents a minimal invasive alternative to other more invasive means
of neuromodulation for trigeminal pain such as motor cortex stimulation or deep
brain stimulation.
PMID- 28518085
TI - Analysis of Chromosome Segregation, Histone Acetylation, and Spindle Morphology
in Horse Oocytes.
AB - The field of assisted reproduction has been developed to treat infertility in
women, companion animals, and endangered species. In the horse, assisted
reproduction also allows for the production of embryos from high performers
without interrupting their sports career and contributes to an increase in the
number of foals from mares of high genetic value. The present manuscript
describes the procedures used for collecting immature and mature oocytes from
horse ovaries using ovum pick-up (OPU). These oocytes were then used to
investigate the incidence of aneuploidy by adapting a protocol previously
developed in mice. Specifically, the chromosomes and the centromeres of metaphase
II (MII) oocytes were fluorescently labeled and counted on sequential focal plans
after confocal laser microscope scanning. This analysis revealed a higher
incidence in the aneuploidy rate when immature oocytes were collected from the
follicles and matured in vitro compared to in vivo. Immunostaining for tubulin
and the acetylated form of histone four at specific lysine residues also revealed
differences in the morphology of the meiotic spindle and in the global pattern of
histone acetylation. Finally, the expression of mRNAs coding for histone
deacetylases (HDACs) and acetyl-transferases (HATs) was investigated by reverse
transcription and quantitative-PCR (q-PCR). No differences in the relative
expression of transcripts were observed between in vitro and in vivo matured
oocytes. In agreement with a general silencing of the transcriptional activity
during oocyte maturation, the analysis of the total transcript amount can only
reveal mRNA stability or degradation. Therefore, these findings indicate that
other translational and post-translational regulations might be affected.
Overall, the present study describes an experimental approach to morphologically
and biochemically characterize the horse oocyte, a cell type that is extremely
challenging to study due to low sample availability. However, it can expand our
knowledge on the reproductive biology and infertility in monovulatory species.
PMID- 28518086
TI - PTR-ToF-MS Coupled with an Automated Sampling System and Tailored Data Analysis
for Food Studies: Bioprocess Monitoring, Screening and Nose-space Analysis.
AB - Proton Transfer Reaction (PTR), combined with a Time-of-Flight (ToF) Mass
Spectrometer (MS) is an analytical approach based on chemical ionization that
belongs to the Direct-Injection Mass Spectrometric (DIMS) technologies. These
techniques allow the rapid determination of volatile organic compounds (VOCs),
assuring high sensitivity and accuracy. In general, PTR-MS requires neither
sample preparation nor sample destruction, allowing real time and non-invasive
analysis of samples. PTR-MS are exploited in many fields, from environmental and
atmospheric chemistry to medical and biological sciences. More recently, we
developed a methodology based on coupling PTR-ToF-MS with an automated sampler
and tailored data analysis tools, to increase the degree of automation and,
consequently, to enhance the potential of the technique. This approach allowed us
to monitor bioprocesses (e.g. enzymatic oxidation, alcoholic fermentation), to
screen large sample sets (e.g. different origins, entire germoplasms) and to
analyze several experimental modes (e.g. different concentrations of a given
ingredient, different intensities of a specific technological parameter) in terms
of VOC content. Here, we report the experimental protocols exemplifying different
possible applications of our methodology: i.e. the detection of VOCs released
during lactic acid fermentation of yogurt (on-line bioprocess monitoring), the
monitoring of VOCs associated with different apple cultivars (large-scale
screening), and the in vivo study of retronasal VOC release during coffee
drinking (nosespace analysis).
PMID- 28518087
TI - Multimer-PAGE: A Method for Capturing and Resolving Protein Complexes in
Biological Samples.
AB - There are many well-developed methods for purifying and studying single proteins
and peptides. However, most cellular functions are carried out by networks of
interacting protein complexes, which are often difficult to investigate because
their binding is non-covalent and easily perturbed by purification techniques.
This work describes a method of stabilizing and separating native protein
complexes from unmodified tissue using two-dimensional polyacrylamide gel
electrophoresis. Tissue lysate is loaded onto a non-denaturing blue-native
polyacrylamide gel, then an electric current is applied until the protein
migrates a short distance into the gel. The gel strip containing the migrated
protein is then excised and incubated with the amine-reactive cross-linking
reagent dithiobis(succinimidyl propionate), which covalently stabilizes protein
complexes. The gel strip containing cross-linked complexes is then cast into a
sodium dodecyl sulfate polyacrylamide gel, and the complexes are separated
completely. The method relies on techniques and materials familiar to most
molecular biologists, meaning it is inexpensive and easy to learn. While it is
limited in its ability to adequately separate extremely large complexes, and has
not been universally successful, the method was able to capture a wide variety of
well-studied complexes, and is likely applicable to many systems of interest.
PMID- 28518088
TI - In Vitro Methods for Comparing Target Binding and CDC Induction Between
Therapeutic Antibodies: Applications in Biosimilarity Analysis.
AB - Therapeutic monoclonal antibodies (mAbs) are relevant to the treatment of
different pathologies, including cancers. The development of biosimilar mAbs by
pharmaceutical companies is a market opportunity, but it is also a strategy to
increase drug accessibility and reduce therapy-associated costs. The protocols
detailed here describe the evaluation of target binding and CDC induction by
rituximab in Daudi cells. These two functions require different structural
regions of the antibody and are relevant to the clinical effect induced by
rituximab. The protocols allow the side-to-side comparison of a reference
rituximab and a marketed rituximab biosimilar. The evaluated products showed
differences both in target binding and CDC induction, suggesting that there are
underlying physicochemical differences and highlighting the need to analyze the
impact of those differences in the clinical setting. The methods reported here
constitute simple and inexpensive in vitro models for the evaluation of the
activity of rituximab biosimilars. Thus, they can be useful during biosimilar
development, as well as for quality control in biosimilar production.
Furthermore, the presented methods can be extrapolated to other therapeutic mAbs.
PMID- 28518089
TI - Laparoscopic Technique for Serial Collection of Liver and Mesenteric Lymph Nodes
in Macaques.
AB - The mesenteric lymph nodes (MLN) and the liver are exposed to microbes and
microbial products from the gastrointestinal (GI) tract, making them
immunologically unique. The GI tract and associated MLN are sites of early viral
replication in human immunodeficiency virus (HIV) infection and the MLN are
likely important reservoir sites that harbor latently-infected cells even after
prolonged antiretroviral therapy (ART). The liver has been shown to play a
significant role in immune responses to lentiviruses and appears to play a
significant role in clearance of virus from circulation. Nonhuman primate (NHP)
models for HIV and Acquired Immunodeficiency Syndrome (AIDS) closely mimic these
aspects of HIV infection and serial longitudinal sampling of primary sites of
viral replication and the associated immune responses in this model will help to
elucidate critical events in infection, pathogenesis, and the impact of various
intervention strategies on these events. Current published techniques to sample
liver and MLN together involve major surgery and/or necropsy, which limits the
ability to investigate these important sites in a serial fashion in the same
animal. We have previously described a laparoscopic technique for collection of
MLN. Here, we describe a minimally invasive laparoscopic technique for serial
longitudinal sampling of liver and MLN through the same two port locations
required for the collection of MLN. The use of the same two ports minimizes the
impact to the animals as no additional incisions are required. This technique can
be used with increased sampling frequency compared to major abdominal surgery and
reduces the potential for surgical complications and associated local and
systemic inflammatory responses that could complicate interpretation of results.
This procedure has potential to facilitate studies involving NHP models while
improving animal welfare.
PMID- 28518090
TI - Flash-and-Freeze: A Novel Technique to Capture Membrane Dynamics with Electron
Microscopy.
AB - Cells constantly change their membrane architecture and protein distribution, but
it is extremely difficult to visualize these events at a temporal and spatial
resolution on the order of ms and nm, respectively. We have developed a time
resolved electron microscopy technique, "flash-and-freeze," that induces cellular
events with optogenetics and visualizes the resulting membrane dynamics by
freezing cells at defined time points after stimulation. To demonstrate this
technique, we expressed channelrhodopsin, a light-sensitive cation channel, in
mouse hippocampal neurons. A flash of light stimulates neuronal activity and
induces neurotransmitter release from synaptic terminals through the fusion of
synaptic vesicles. The optogenetic stimulation of neurons is coupled with high
pressure freezing to follow morphological changes during synaptic transmission.
Using a commercial instrument, we captured the fusion of synaptic vesicles and
the recovery of the synaptic vesicle membrane. To visualize the sequence of
events, large datasets were generated and analyzed blindly, since morphological
changes were followed in different cells over time. Nevertheless, flash-and
freeze allows the visualization of membrane dynamics in electron micrographs with
ms temporal resolution.
PMID- 28518091
TI - Long-term Live Imaging of Drosophila Eye Disc.
AB - Live imaging provides the ability to continuously track dynamic cellular and
developmental processes in real time. Drosophila larval imaginal discs have been
used to study many biological processes, such as cell proliferation,
differentiation, growth, migration, apoptosis, competition, cell-cell signaling,
and compartmental boundary formation. However, methods for the long-term ex vivo
culture and live imaging of the imaginal discs have not been satisfactory,
despite many efforts. Recently, we developed a method for the long-term ex vivo
culture and live imaging of imaginal discs for up to 18 h. In addition to using a
high insulin concentration in the culture medium, a low-melting agarose was also
used to embed the disc to prevent it from drifting during the imaging period.
This report uses the eye-antennal discs as an example. Photoreceptor R3/4
specific mdelta0.5-Ga4 expression was followed to demonstrate that photoreceptor
differentiation and ommatidial rotation can be observed during a 10 h live
imaging period. This is a detailed protocol describing this simple method.
PMID- 28518092
TI - Isolation of the Side Population in Myc-induced T-cell Acute Lymphoblastic
Leukemia in Zebrafish.
AB - Heterogeneous cell populations, from either healthy or malignant tissues, may
contain a population of cells characterized by a differential ability to efflux
the DNA-binding dye Hoechst 33342. This "side population" of cells can be
identified using flow cytometric methods after the Hoechst 33342 dye is excited
by an ultraviolet (UV) laser. The side population of many cell types contains
stem- or progenitor-like cells. However, not all cell types have an identifiable
side population. Danio rerio, zebrafish, have a robust in vivo model of T-cell
acute lymphoblastic leukemia (T-ALL), but whether these zebrafish T-ALLs have a
side population is unknown. The method described here outlines how to isolate the
side population cells in zebrafish T-ALL. To begin, the T-ALL in zebrafish is
generated via the microinjection of tol2 plasmids into one-cell stage embryos.
Once the tumors have grown to a stage at which they expand into more than half of
the animal's body, the T-ALL cells can be harvested. The cells are then stained
with Hoechst 33342 and examined by flow cytometry for side population cells. This
method has broad applications in zebrafish T-ALL research. While there are no
known cell surface markers in zebrafish that confirm whether these side
population cells are cancer stem cell-like, in vivo functional transplantation
assays are possible. Furthermore, single-cell transcriptomics could be applied to
identify the genetic features of these side population cells.
PMID- 28518093
TI - Determining the Optimal Inhibitory Frequency for Cancerous Cells Using Tumor
Treating Fields (TTFields).
AB - Tumor Treating Fields (TTFields) are an effective treatment modality delivered
via the continuous, noninvasive application of low-intensity (1-3 V/cm),
alternating electric fields in the frequency range of several hundred kHz. The
study of TTFields in tissue culture is carried out using the TTFields in vitro
application system, which allows for the application of electric fields of
varying frequencies and intensities to ceramic Petri dishes with a high
dielectric constant (E > 5,000). Cancerous cell lines plated on coverslips at the
bottom of the ceramic Petri dishes are subjected to TTFields delivered in two
orthogonal directions at various frequencies to facilitate treatment outcome
tests, such as cell counts and clonogenic assays. The results presented in this
report demonstrate that the optimal frequency of the TTFields with respect to
both cell counts and clonogenic assays is 200 kHz for both ovarian and glioma
cells.
PMID- 28518095
TI - Use of a Central Venous Line for Fluids, Drugs and Nutrient Administration in a
Mouse Model of Critical Illness.
AB - This protocol describes a centrally catheterized mouse model of prolonged
critical illness. We combine the cecal ligation and puncture method to induce
sepsis with the use of a central venous line for fluids, drugs and nutrient
administration to mimic the human clinical setting. Critically ill patients
require intensive medical support in order to survive. While the majority of
patients will recover within a few days, about a quarter of the patients need
prolonged intensive care and are at high risk of dying from non-resolving
multiple organ failure. Furthermore, the prolonged phase of critical illness is
hallmarked by profound muscle weakness, and endocrine and metabolic changes, of
which the pathogenesis is currently incompletely understood. The most widely used
animal model in critical care research is the cecal ligation and puncture model
to induce sepsis. This is a very reproducible model, with acute inflammatory and
hemodynamic changes similar to human sepsis, which is designed to study the acute
phase of critical illness. However, this model is hallmarked by a high lethality,
which is different from the clinical human situation, and is not developed to
study the prolonged phase of critical illness. Therefore, we adapted the
technique by placing a central venous catheter in the jugular vein allowing us to
administer clinically relevant supportive care, to better mimic the human
clinical situation of critical illness. This mouse model requires an extensive
surgical procedure and daily intensive care of the animals, but it results in a
relevant model of the acute and prolonged phase of critical illness.
PMID- 28518094
TI - A Within-subjects Experimental Protocol to Assess the Effects of Social Input on
Infant EEG.
AB - Despite the importance of social interactions for infant brain development,
little research has assessed functional neural activation while infants socially
interact. Electroencephalography (EEG) power is an advantageous technique to
assess infant functional neural activation. However, many studies record infant
EEG only during one baseline condition. This protocol describes a paradigm that
is designed to comprehensively assess infant EEG activity in both social and
nonsocial contexts as well as tease apart how different types of social inputs
differentially relate to infant EEG. The within-subjects paradigm includes four
controlled conditions. In the nonsocial condition, infants view objects on
computer screens. The joint attention condition involves an experimenter
directing the infant's attention to pictures. The joint attention condition
includes three types of social input: language, face-to-face interaction, and the
presence of joint attention. Differences in infant EEG between the nonsocial and
joint attention conditions could be due to any of these three types of input.
Therefore, two additional conditions (one with language input while the
experimenter is hidden behind a screen and one with face-to-face interaction)
were included to assess the driving contextual factors in patterns of infant
neural activation. Representative results demonstrate that infant EEG power
varied by condition, both overall and differentially by brain region, supporting
the functional nature of infant EEG power. This technique is advantageous in that
it includes conditions that are clearly social or nonsocial and allows for
examination of how specific types of social input relate to EEG power. This
paradigm can be used to assess how individual differences in age, affect,
socioeconomic status, and parent-infant interaction quality relate to the
development of the social brain. Based on the demonstrated functional nature of
infant EEG power, future studies should consider the role of EEG recording
context and design conditions that are clearly social or nonsocial.
PMID- 28518096
TI - Invasive Behavior of Human Breast Cancer Cells in Embryonic Zebrafish.
AB - In many cases, cancer patients do not die of a primary tumor, but rather because
of metastasis. Although numerous rodent models are available for studying cancer
metastasis in vivo, other efficient, reliable, low-cost models are needed to
quickly access the potential effects of (epi)genetic changes or pharmacological
compounds. As such, we illustrate and explain the feasibility of xenograft models
using human breast cancer cells injected into zebrafish embryos to support this
goal. Under the microscope, fluorescent proteins or chemically labeled human
breast cancer cells are transplanted into transgenic zebrafish embryos, Tg
(fli:EGFP), at the perivitelline space or duct of Cuvier (Doc) 48 h after
fertilization. Shortly afterwards, the temporal-spatial process of cancer cell
invasion, dissemination, and metastasis in the living fish body is visualized
under a fluorescent microscope. The models using different injection sites, i.e.,
perivitelline space or Doc are complementary to one another, reflecting the early
stage (intravasation step) and late stage (extravasation step) of the multistep
metastatic cascade of events. Moreover, peritumoral and intratumoral angiogenesis
can be observed with the injection into the perivitelline space. The entire
experimental period is no more than 8 days. These two models combine cell
labeling, micro-transplantation, and fluorescence imaging techniques, enabling
the rapid evaluation of cancer metastasis in response to genetic and
pharmacological manipulations.
PMID- 28518098
TI - Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in
Human Cells.
AB - The processing of most eukaryotic RNAs is mediated by RNA Binding Proteins (RBPs)
with modular configurations, including an RNA recognition module, which
specifically binds the pre-mRNA target and an effector domain. Previously, we
have taken advantage of the unique RNA binding mode of the PUF domain in human
Pumilio 1 to generate a programmable RNA binding scaffold, which was used to
engineer various artificial RBPs to manipulate RNA metabolism. Here, a detailed
protocol is described to construct Engineered Splicing Factors (ESFs) that are
specifically designed to modulate the alternative splicing of target genes. The
protocol includes how to design and construct a customized PUF scaffold for a
specific RNA target, how to construct an ESF expression plasmid by fusing a
designer PUF domain and an effector domain, and how to use ESFs to manipulate the
splicing of target genes. In the representative results of this method, we have
also described the common assays of ESF activities using splicing reporters, the
application of ESF in cultured human cells, and the subsequent effect of splicing
changes. By following the detailed protocols in this report, it is possible to
design and generate ESFs for the regulation of different types of Alternative
Splicing (AS), providing a new strategy to study splicing regulation and the
function of different splicing isoforms. Moreover, by fusing different functional
domains with a designed PUF domain, researchers can engineer artificial factors
that target specific RNAs to manipulate various steps of RNA processing.
PMID- 28518099
TI - Dissection of Larval Zebrafish Gonadal Tissue.
AB - Although wild zebrafish possess a ZZ/ZW sex-determination system, domesticated
zebrafish have lost the sex chromosome. They utilize a polygenic sex
determination system, where several genes distributed throughout the genome
collectively determine the sex identities of individual fish. Currently, the
genes involved in regulating gonad development and how they work remain elusive.
Normally, isolating gonadal tissue is the first step to examine the sex
developmental processes. Here, we present a procedure to isolate gonadal tissue
from 17 dpf (days post fertilization) and 25 dpf zebrafish larvae. The isolated
gonadal tissue may be subsequently examined by morphology and gene expression
profiling.
PMID- 28518097
TI - Light Sheet-based Fluorescence Microscopy of Living or Fixed and Stained
Tribolium castaneum Embryos.
AB - The red flour beetle Tribolium castaneum has become an important insect model
organism in developmental genetics and evolutionary developmental biology. The
observation of Tribolium embryos with light sheet-based fluorescence microscopy
has multiple advantages over conventional widefield and confocal fluorescence
microscopy. Due to the unique properties of a light sheet-based microscope, three
dimensional images of living specimens can be recorded with high signal-to-noise
ratios and significantly reduced photo-bleaching as well as photo-toxicity along
multiple directions over periods that last several days. With more than four
years of methodological development and a continuous increase of data, the time
seems appropriate to establish standard operating procedures for the usage of
light sheet technology in the Tribolium community as well as in the insect
community at large. This protocol describes three mounting techniques suitable
for different purposes, presents two novel custom-made transgenic Tribolium lines
appropriate for long-term live imaging, suggests five fluorescent dyes to label
intracellular structures of fixed embryos and provides information on data post
processing for the timely evaluation of the recorded data. Representative results
concentrate on long-term live imaging, optical sectioning and the observation of
the same embryo along multiple directions. The respective datasets are provided
as a downloadable resource. Finally, the protocol discusses quality controls for
live imaging assays, current limitations and the applicability of the outlined
procedures to other insect species. This protocol is primarily intended for
developmental biologists who seek imaging solutions that outperform standard
laboratory equipment. It promotes the continuous attempt to close the gap between
the technically orientated laboratories/communities, which develop and refine
microscopy methodologically, and the life science laboratories/communities, which
require 'plug-and-play' solutions to technical challenges. Furthermore, it
supports an axiomatic approach that moves the biological questions into the
center of attention.
PMID- 28518100
TI - TiO2-coated Hollow Glass Microspheres with Superhydrophobic and High IR
reflective Properties Synthesized by a Soft-chemistry Method.
AB - This manuscript proposes a soft-chemistry method to develop superhydrophobic and
highly IR-reflective hollow glass microspheres (HGM). The anatase TiO2 and a
superhydrophobic agent were coated on the HGM surface in one step. TBT and PFOTES
were selected as the Ti source and the superhydrophobic agent, respectively. They
were both coated on the HGM, and after the hydrothermal process, the TBT turned
to anatase TiO2. In this way, a PFOTES/TiO2-coated HGM (MCHGM) was prepared. For
comparison, PFOTES single-coated HGM (F-SCHGM) and TiO2 single-coated HGM (Ti
SCHGM) were synthesized as well. The PFOTES and TiO2 coatings on the HGM surface
were demonstrated through X-ray diffraction (XRD), scanning electron microscopy
(SEM), and energy-dispersive detector (EDS) characterizations. The MCHGM showed a
higher contact angle (153 degrees ) but a lower sliding angle (16 degrees ) than
F-SCHGM, with a contact angle of 141.2 degrees and a sliding angle of 67 degrees
. In addition, both Ti-SCHGM and MCHGM displayed similar IR reflectivity values,
which were about 5.8% higher than the original HGM and F-SCHGM. Also, the PFOTES
coating barely changed the thermal conductivity. Therefore, F-SCHGM, with a
thermal conductivity of 0.0479 W/(m.K), was quite like the original HGM, which
was 0.0475 W/(m.K). MCHGM and Ti-SCHGM were also similar. Their thermal
conductivity values were 0.0543 W/(m.K) and 0.0543 W/(m.K), respectively. The
TiO2 coating slightly increased the thermal conductivity, but with the increase
in reflectivity, the overall heat-insulation property was enhanced. Finally,
since the IR-reflecting property is provided by the HGM coating, if the coating
is fouled, the reflectivity decreases. Therefore, with the superhydrophobic
coating, the surface is protected from fouling, and its lifetime is also
prolonged.
PMID- 28518102
TI - NMR Spectroscopy as a Robust Tool for the Rapid Evaluation of the Lipid Profile
of Fish Oil Supplements.
AB - The western diet is poor in n-3 fatty acids, therefore the consumption of fish
oil supplements is recommended to increase the intake of these essential
nutrients. The objective of this work is to demonstrate the qualitative and
quantitative analysis of encapsulated fish oil supplements using high-resolution
1H and 13C NMR spectroscopy utilizing two different NMR instruments; a 500 MHz
and an 850 MHz instrument. Both proton (1H) and carbon (13C) NMR spectra can be
used for the quantitative determination of the major constituents of fish oil
supplements. Quantification of the lipids in fish oil supplements is achieved
through integration of the appropriate NMR signals in the relevant 1D spectra.
Results obtained by 1H and 13C NMR are in good agreement with each other, despite
the difference in resolution and sensitivity between the two nuclei and the two
instruments. 1H NMR offers a more rapid analysis compared to 13C NMR, as the
spectrum can be recorded in less than 1 min, in contrast to 13C NMR analysis,
which lasts from 10 min to one hour. The 13C NMR spectrum, however, is much more
informative. It can provide quantitative data for a greater number of individual
fatty acids and can be used for determining the positional distribution of fatty
acids on the glycerol backbone. Both nuclei can provide quantitative information
in just one experiment without the need of purification or separation steps. The
strength of the magnetic field mostly affects the 1H NMR spectra due to its lower
resolution with respect to 13C NMR, however, even lower cost NMR instruments can
be efficiently applied as a standard method by the food industry and quality
control laboratories.
PMID- 28518101
TI - Using Wavelet Entropy to Demonstrate how Mindfulness Practice Increases
Coordination between Irregular Cerebral and Cardiac Activities.
AB - In both the East and West, traditional teachings say that the mind and heart are
somehow closely correlated, especially during spiritual practice. One difficulty
in proving this objectively is that the natures of brain and heart activities are
quite different. In this paper, we propose a methodology that uses wavelet
entropy to measure the chaotic levels of both electroencephalogram (EEG) and
electrocardiogram (ECG) data and show how this may be used to explore the
potential coordination between the mind and heart under different experimental
conditions. Furthermore, Statistical Parametric Mapping (SPM) was used to
identify the brain regions in which the EEG wavelet entropy was the most affected
by the experimental conditions. As an illustration, the EEG and ECG were recorded
under two different conditions (normal rest and mindful breathing) at the
beginning of an 8-week standard Mindfulness-based Stress Reduction (MBSR)
training course (pretest) and after the course (posttest). Using the proposed
method, the results consistently showed that the wavelet entropy of the brain EEG
decreased during the MBSR mindful breathing state as compared to that during the
closed-eye resting state. Similarly, a lower wavelet entropy of heartrate was
found during MBSR mindful breathing. However, no difference in wavelet entropy
during MBSR mindful breathing was found between the pretest and posttest. No
correlation was observed between the entropy of brain waves and the entropy of
heartrate during normal rest in all participants, whereas a significant
correlation was observed during MBSR mindful breathing. Additionally, the most
well-correlated brain regions were located in the central areas of the brain.
This study provides a methodology for the establishment of evidence that
mindfulness practice (i.e., mindful breathing) may increase the coordination
between mind and heart activities.
PMID- 28518103
TI - Structure-function Studies in Mouse Embryonic Stem Cells Using Recombinase
mediated Cassette Exchange.
AB - Gene engineering in mouse embryos or embryonic stem cells (mESCs) allows for the
study of the function of a given protein. Proteins are the workhorses of the cell
and often consist of multiple functional domains, which can be influenced by
posttranslational modifications. The depletion of the entire protein in
conditional or constitutive knock-out (KO) mice does not take into account this
functional diversity and regulation. An mESC line and a derived mouse model, in
which a docking site for FLPe recombination-mediated cassette exchange (RMCE) was
inserted within the ROSA26 (R26) locus, was previously reported. Here, we report
on a structure-function approach that allows for molecular dissection of the
different functionalities of a multidomain protein. To this end, RMCE-compatible
mice must be crossed with KO mice and then RMCE-compatible KO mESCs must be
isolated. Next, a panel of putative rescue constructs can be introduced into the
R26 locus via RMCE targeting. The candidate rescue cDNAs can be easily inserted
between RMCE sites of the targeting vector using recombination cloning. Next, KO
mESCs are transfected with the targeting vector in combination with an FLPe
recombinase expression plasmid. RMCE reactivates the promoter-less neomycin
resistance gene in the ROSA26 docking sites and allows for the selection of the
correct targeting event. In this way, high targeting efficiencies close to 100%
are obtained, allowing for insertion of multiple putative rescue constructs in a
semi-high throughput manner. Finally, a multitude of R26-driven rescue constructs
can be tested for their ability to rescue the phenotype that was observed in
parental KO mESCs. We present a proof-of-principle structure-function study in
p120 catenin (p120ctn) KO mESCs using endoderm differentiation in embryoid bodies
(EBs) as the phenotypic readout. This approach enables the identification of
important domains, putative downstream pathways, and disease-relevant point
mutations that underlie KO phenotypes for a given protein.
PMID- 28518104
TI - Neurodevelopmental Reflex Testing in Neonatal Rat Pups.
AB - Neurodevelopmental reflex testing is commonly used in clinical practice to assess
the maturation of the nervous system. Neurodevelopmental reflexes are also
referred to as primitive reflexes. They are sensitive and consistent with later
outcomes. Abnormal reflexes are described as an absence, persistence,
reappearance, or latency of reflexes, which are predictive indices of infants
that are at high risk for neurodevelopmental disorders. Animal models of
neurodevelopmental disabilities, such as cerebral palsy, often display aberrant
developmental reflexes, as would be observed in human infants. The techniques
described assess a variety of neurodevelopmental reflexes in neonatal rats.
Neurodevelopmental reflex testing offers the investigator a testing method that
is not otherwise available in such young animals. The methodology presented here
aims to assist investigators in examining developmental milestones in neonatal
rats as a method of detecting early-onset brain injury and/or determining the
effectiveness of therapeutic interventions. The methodology presented here aims
to provide a general guideline for investigators.
PMID- 28518106
TI - Isolation of Murine Adipose Tissue-derived Microvascular Fragments as
Vascularization Units for Tissue Engineering.
AB - A functional microvascular network is of pivotal importance for the survival and
integration of engineered tissue constructs. For this purpose, several angiogenic
and prevascularization strategies have been established. However, most cell-based
approaches include time-consuming in vitro steps for the formation of a
microvascular network. Hence, they are not suitable for intraoperative one-step
procedures. Adipose tissue-derived microvascular fragments (ad-MVF) represent
promising vascularization units. They can be easily isolated from fat tissue and
exhibit a functional microvessel morphology. Moreover, they rapidly reassemble
into new microvascular networks after in vivo implantation. In addition, ad-MVF
have been shown to induce lymphangiogenesis. Finally, they are a rich source of
mesenchymal stem cells, which may further contribute to their high
vascularization potential. In previous studies we have demonstrated the
remarkable vascularization capacity of ad-MVF in engineered bone and skin
substitutes. In the present study, we report on a standardized protocol for the
enzymatic isolation of ad-MVF from murine fat tissue.
PMID- 28518107
TI - A Large Lateral Craniotomy Procedure for Mesoscale Wide-field Optical Imaging of
Brain Activity.
AB - The craniotomy is a commonly performed procedure to expose the brain for in vivo
experiments. In mouse research, most labs utilize a small craniotomy, typically 3
mm x 3 mm. This protocol introduces a method for creating a substantially larger
7 mm x 6 mm cranial window exposing most of a cerebral hemisphere over the mouse
temporal and parietal cortices (e.g., bregma 2.5 - 4.5 mm, lateral 0 - 6 mm). To
perform this surgery, the head must be tilted approximately 30 degrees and much
of the temporal muscle must be retracted. Due to the large amount of bone
removal, this procedure is intended only for acute experiments with the animal
anesthetized throughout the surgery and experiment. The main advantage of this
innovative large lateral cranial window is to provide simultaneous access to both
medial and lateral areas of the cortex. This large unilateral cranial window can
be used to study the neural dynamics between cells, as well as between different
cortical areas by combining multi-electrode electrophysiological recordings,
imaging of neuronal activity (e.g., intrinsic or extrinsic imaging), and
optogenetic stimulation. Additionally, this large craniotomy also exposes a large
area of cortical blood vessels, allowing for direct manipulation of the lateral
cortical vasculature.
PMID- 28518105
TI - Murine Lymphocyte Labeling by 64Cu-Antibody Receptor Targeting for In Vivo Cell
Trafficking by PET/CT.
AB - This protocol illustrates the production of 64Cu and the chelator
conjugation/radiolabeling of a monoclonal antibody (mAb) followed by murine
lymphocyte cell culture and 64Cu-antibody receptor targeting of the cells. In
vitro evaluation of the radiolabel and non-invasive in vivo cell tracking in an
animal model of an airway delayed-type hypersensitivity reaction (DTHR) by PET/CT
are described. In detail, the conjugation of a mAb with the chelator 1,4,7,10
tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) is shown. Following the
production of radioactive 64Cu, radiolabeling of the DOTA-conjugated mAb is
described. Next, the expansion of chicken ovalbumin (cOVA)-specific CD4+
interferon (IFN)-gamma-producing T helper cells (cOVA-TH1) and the subsequent
radiolabeling of the cOVA-TH1 cells are depicted. Various in vitro techniques are
presented to evaluate the effects of 64Cu-radiolabeling on the cells, such as the
determination of cell viability by trypan blue exclusion, the staining for
apoptosis with Annexin V for flow cytometry, and the assessment of functionality
by IFN-gamma enzyme-linked immunosorbent assay (ELISA). Furthermore, the
determination of the radioactive uptake into the cells and the labeling stability
are described in detail. This protocol further describes how to perform cell
tracking studies in an animal model for an airway DTHR and, therefore, the
induction of cOVA-induced acute airway DHTR in BALB/c mice is included. Finally,
a robust PET/CT workflow including image acquisition, reconstruction, and
analysis is presented. The 64Cu-antibody receptor targeting approach with
subsequent receptor internalization provides high specificity and stability,
reduced cellular toxicity, and low efflux rates compared to common PET-tracers
for cell labeling, e.g.64Cu-pyruvaldehyde bis(N4-methylthiosemicarbazone) (64Cu
PTSM). Finally, our approach enables non-invasive in vivo cell tracking by PET/CT
with an optimal signal-to-background ratio for 48 h. This experimental approach
can be transferred to different animal models and cell types with membrane-bound
receptors that are internalized.
PMID- 28518108
TI - Identification of Plant Ice-binding Proteins Through Assessment of Ice
recrystallization Inhibition and Isolation Using Ice-affinity Purification.
AB - Ice-binding proteins (IBPs) belong to a family of stress-induced proteins that
are synthesized by certain organisms exposed to subzero temperatures. In plants,
freeze damage occurs when extracellular ice crystals grow, resulting in the
rupture of plasma membranes and possible cell death. Adsorption of IBPs to ice
crystals restricts further growth by a process known as ice-recrystallization
inhibition (IRI), thereby reducing cellular damage. IBPs also demonstrate the
ability to depress the freezing point of a solution below the equilibrium melting
point, a property known as thermal hysteresis (TH) activity. These protective
properties have raised interest in the identification of novel IBPs due to their
potential use in industrial, medical and agricultural applications. This paper
describes the identification of plant IBPs through 1) the induction and
extraction of IBPs in plant tissue, 2) the screening of extracts for IRI
activity, and 3) the isolation and purification of IBPs. Following the induction
of IBPs by low temperature exposure, extracts are tested for IRI activity using a
'splat assay', which allows the observation of ice crystal growth using a
standard light microscope. This assay requires a low protein concentration and
generates results that are quickly obtained and easily interpreted, providing an
initial screen for ice binding activity. IBPs can then be isolated from
contaminating proteins by utilizing the property of IBPs to adsorb to ice,
through a technique called 'ice-affinity purification'. Using cell lysates
collected from plant extracts, an ice hemisphere can be slowly grown on a brass
probe. This incorporates IBPs into the crystalline structure of the
polycrystalline ice. Requiring no a priori biochemical or structural knowledge of
the IBP, this method allows for recovery of active protein. Ice-purified protein
fractions can be used for downstream applications including the identification of
peptide sequences by mass spectrometry and the biochemical analysis of native
proteins.
PMID- 28518109
TI - Assessment of Neuronal Viability Using Fluorescein Diacetate-Propidium Iodide
Double Staining in Cerebellar Granule Neuron Culture.
AB - Primary cultured Cerebellar Granule Neurons (CGNs) have been widely used as an in
vitro model in neuroscience and neuropharmacology research. However, the co
existence of glial cells and neurons in CGN culture might lead to biases in the
accurate assessment of neuronal viability. Fluorescein diacetate (FDA) and
Propidium Iodide (PI) double staining has been used to measure cell viability by
simultaneously evaluating the viable and dead cells. We used FDA-PI double
staining to improve the sensitivities of the colorimetric assays and to evaluate
neuronal viability in CGNs. Furthermore, we added blue fluorescent DNA stains
(e.g., Hoechst) to improve the accuracy. This protocol describes how to improve
the accuracy of assessment of neuronal viability by using these methods in CGN
culture. Using this protocol, the number of glial cells can be excluded by using
fluorescence microscopy. A similar strategy can be applied to distinguish the
unwanted glial cells from neurons in various mixed cell cultures, such as primary
cortical culture and hippocampal culture.
PMID- 28518110
TI - External Excitation of Neurons Using Electric and Magnetic Fields in One- and Two
dimensional Cultures.
AB - A neuron will fire an action potential when its membrane potential exceeds a
certain threshold. In typical activity of the brain, this occurs as a result of
chemical inputs to its synapses. However, neurons can also be excited by an
imposed electric field. In particular, recent clinical applications activate
neurons by creating an electric field externally. It is therefore of interest to
investigate how the neuron responds to the external field and what causes the
action potential. Fortunately, precise and controlled application of an external
electric field is possible for embryonic neuronal cells that are excised,
dissociated and grown in cultures. This allows the investigation of these
questions in a highly reproducible system. In this paper some of the techniques
used for controlled application of external electric field on neuronal cultures
are reviewed. The networks can be either one dimensional, i.e. patterned in
linear forms or allowed to grow on the whole plane of the substrate, and thus two
dimensional. Furthermore, the excitation can be created by the direct application
of electric field via electrodes immersed in the fluid (bath electrodes) or by
inducing the electric field using the remote creation of magnetic pulses.
PMID- 28518111
TI - Using Enzyme-based Biosensors to Measure Tonic and Phasic Glutamate in
Alzheimer's Mouse Models.
AB - Neurotransmitter disruption is often a key component of diseases of the central
nervous system (CNS), playing a role in the pathology underlying Alzheimer's
disease, Parkinson's disease, depression, and anxiety. Traditionally,
microdialysis has been the most common (lauded) technique to examine
neurotransmitter changes that occur in these disorders. But because microdialysis
has the ability to measure slow 1-20 minute changes across large areas of tissue,
it has the disadvantage of invasiveness, potentially destroying intrinsic
connections within the brain and a slow sampling capability. A relatively newer
technique, the microelectrode array (MEA), has numerous advantages for measuring
specific neurotransmitter changes within discrete brain regions as they occur,
making for a spatially and temporally precise approach. In addition, using MEAs
is minimally invasive, allowing for measurement of neurotransmitter alterations
in vivo. In our laboratory, we have been specifically interested in changes in
the neurotransmitter, glutamate, related to Alzheimer's disease pathology. As
such, the method described here has been used to assess potential hippocampal
disruptions in glutamate in a transgenic mouse model of Alzheimer's disease.
Briefly, the method used involves coating a multi-site microelectrode with an
enzyme very selective for the neurotransmitter of interest and using self
referencing sites to subtract out background noise and interferents. After
plating and calibration, the MEA can be constructed with a micropipette and
lowered into the brain region of interest using a stereotaxic device. Here, the
method described involves anesthetizing rTg(TauP301L)4510 mice and using a
stereotaxic device to precisely target sub-regions (DG, CA1, and CA3) of the
hippocampus.
PMID- 28518112
TI - Functional Manipulation of Maternal Gene Products Using In Vitro Oocyte
Maturation in Zebrafish.
AB - Cellular events that take place during the earliest stages of animal embryonic
development are driven by maternally derived gene products deposited into the
developing oocyte. Because these events rely on maternal products which typically
act very soon after fertilization-that preexist inside the egg, standard
approaches for expression and functional reduction involving the injection of
reagents into the fertilized egg are typically ineffective. Instead, such
manipulations must be performed during oogenesis, prior to or during the
accumulation of maternal products. This article describes in detail a protocol
for the in vitro maturation of immature zebrafish oocytes and their subsequent in
vitro fertilization, yielding viable embryos that survive to adulthood. This
method allows the functional manipulation of maternal products during oogenesis,
such as the expression of products for phenotypic rescue and tagged construct
visualization, as well as the reduction of gene function through reverse-genetics
agents.
PMID- 28518113
TI - Enhanced Sample Multiplexing of Tissues Using Combined Precursor Isotopic
Labeling and Isobaric Tagging (cPILOT).
AB - There is an increasing demand to analyze many biological samples for disease
understanding and biomarker discovery. Quantitative proteomics strategies that
allow simultaneous measurement of multiple samples have become widespread and
greatly reduce experimental costs and times. Our laboratory developed a technique
called combined precursor isotopic labeling and isobaric tagging (cPILOT), which
enhances sample multiplexing of traditional isotopic labeling or isobaric tagging
approaches. Global cPILOT can be applied to samples originating from cells,
tissues, bodily fluids, or whole organisms and gives information on relative
protein abundances across different sample conditions. cPILOT works by 1) using
low pH buffer conditions to selectively dimethylate peptide N-termini and 2)
using high pH buffer conditions to label primary amines of lysine residues with
commercially-available isobaric reagents (see Table of Materials/Reagents). The
degree of sample multiplexing available is dependent on the number of precursor
labels used and the isobaric tagging reagent. Here, we present a 12-plex analysis
using light and heavy dimethylation combined with six-plex isobaric reagents to
analyze 12 samples from mouse tissues in a single analysis. Enhanced multiplexing
is helpful for reducing experimental time and cost and more importantly, allowing
comparison across many sample conditions (biological replicates, disease stage,
drug treatments, genotypes, or longitudinal time-points) with less experimental
bias and error. In this work, the global cPILOT approach is used to analyze
brain, heart, and liver tissues across biological replicates from an Alzheimer's
disease mouse model and wild-type controls. Global cPILOT can be applied to study
other biological processes and adapted to increase sample multiplexing to greater
than 20 samples.
PMID- 28518115
TI - Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem
Cells in Two and Three-dimensional Embryoid Bodies.
AB - Mouse embryonic stem cells (ESCs) isolated from the inner mass of the blastocyst
(typically at day E3.5), can be used as in vitro model system for studying early
embryonic development. In the absence of leukemia inhibitory factor (LIF), ESCs
differentiate by default into neural precursor cells. They can be amassed into a
three dimensional (3D) spherical aggregate termed embryoid body (EB) due to its
similarity to the early stage embryo. EBs can be seeded on fibronectin-coated
coverslips, where they expand by growing two dimensional (2D) extensions, or
implanted in 3D collagen matrices where they continue growing as spheroids, and
differentiate into the three germ layers: endodermal, mesodermal, and ectodermal.
The 3D collagen culture mimics the in vivo environment more closely than the 2D
EBs. The 2D EB culture facilitates analysis by immunofluorescence and
immunoblotting to track differentiation. We have developed a two-step neural
differentiation protocol. In the first step, EBs are generated by the hanging
drop technique, and, simultaneously, are induced to differentiate by exposure to
retinoic acid (RA). In the second step, neural differentiation proceeds in a 2D
or 3D format in the absence of RA.
PMID- 28518114
TI - Preparation and In Vitro Characterization of Magnetized miR-modified Endothelial
Cells.
AB - To date, the available surgical and pharmacological treatments for cardiovascular
diseases (CVD) are limited and often palliative. At the same time, gene and cell
therapies are highly promising alternative approaches for CVD treatment. However,
the broad clinical application of gene therapy is greatly limited by the lack of
suitable gene delivery systems. The development of appropriate gene delivery
vectors can provide a solution to current challenges in cell therapy. In
particular, existing drawbacks, such as limited efficiency and low cell retention
in the injured organ, could be overcome by appropriate cell engineering (i.e.,
genetic) prior to transplantation. The presented protocol describes the efficient
and safe transient modification of endothelial cells using a polyethyleneimine
superparamagnetic magnetic nanoparticle (PEI/MNP)-based delivery vector. Also,
the algorithm and methods for cell characterization are defined. The successful
intracellular delivery of microRNA (miR) into human umbilical vein endothelial
cells (HUVECs) has been achieved without affecting cell viability, functionality,
or intercellular communication. Moreover, this approach was proven to cause a
strong functional effect in introduced exogenous miR. Importantly, the
application of this MNP-based vector ensures cell magnetization, with
accompanying possibilities of magnetic targeting and non-invasive MRI tracing.
This may provide a basis for magnetically guided, genetically engineered cell
therapeutics that can be monitored non-invasively with MRI.
PMID- 28518116
TI - The WinCF Model - An Inexpensive and Tractable Microcosm of a Mucus Plugged
Bronchiole to Study the Microbiology of Lung Infections.
AB - Many chronic airway diseases result in mucus plugging of the airways. Lungs of an
individual with cystic fibrosis are an exemplary case where their mucus-plugged
bronchioles create a favorable habitat for microbial colonization. Various
pathogens thrive in this environment interacting with each other and driving many
of the symptoms associated with CF disease. Like any microbial community, the
chemical conditions of their habitat have a significant impact on the community
structure and dynamics. For example, different microorganisms thrive in differing
levels of oxygen or other solute concentrations. This is also true in the CF
lung, where oxygen concentrations are believed to drive community physiology and
structure. The methods described here are designed to mimic the lung environment
and grow pathogens in a manner more similar to that from which they cause
disease. Manipulation of the chemical surroundings of these microbes is then used
to study how the chemistry of lung infections governs its microbial ecology. The
method, called the WinCF system, is based on artificial sputum medium and narrow
capillary tubes meant to provide an oxygen gradient similar to that which exists
in mucus-plugged bronchioles. Manipulating chemical conditions, such as the media
pH of the sputum or antibiotics pressure, allows for visualization of the
microbiological differences in those samples using colored indicators, watching
for gas or biofilm production, or extracting and sequencing the nucleic acid
contents of each sample.
PMID- 28518117
TI - Simultaneous Evaluation of Cerebral Hemodynamics and Light Scattering Properties
of the In Vivo Rat Brain Using Multispectral Diffuse Reflectance Imaging.
AB - The simultaneous evaluation of cerebral hemodynamics and the light scattering
properties of in vivo rat brain tissue is demonstrated using a conventional
multispectral diffuse reflectance imaging system. This system is constructed from
a broadband white light source, a motorized filter wheel with a set of narrowband
interference filters, a light guide, a collecting lens, a video zoom lens, and a
monochromatic charged-coupled device (CCD) camera. An ellipsoidal cranial window
is made in the skull bone of a rat under isoflurane anesthesia to capture in vivo
multispectral diffuse reflectance images of the cortical surface. Regulation of
the fraction of inspired oxygen using a gas mixture device enables the induction
of different respiratory states such as normoxia, hyperoxia, and anoxia. A Monte
Carlo simulation-based multiple regression analysis for the measured
multispectral diffuse reflectance images at nine wavelengths (500, 520, 540, 560,
570, 580, 600, 730, and 760 nm) is then performed to visualize the two
dimensional maps of hemodynamics and the light scattering properties of the in
vivo rat brain.
PMID- 28518118
TI - Harnessing the DNA Dye-triggered Side Population Phenotype to Detect and Purify
Cancer Stem Cells from Biological Samples.
AB - Cancer is a stem cell-driven disease and eradication of these cells has become a
major therapeutic goal. Deciphering vulnerabilities of Cancer Stem Cells (CSCs)
and identifying suitable molecular targets relies on methods that allow their
specific discrimination in heterogeneous samples such as cell lines and ex vivo
tumor tissue. Flow cytometry/FACS is a powerful technology to multi
parametrically dissect biological samples at the single cell level and is to date
the method of choice to recover live cells for downstream analyses. Surface
markers such as CD44 and CD133 as well as detection of aldehyde dehydrogenase
enzymatic activity have often been used to define and sort out CSCs from tumor
samples by FACS. A complementary approach, depicted here in methodological
detail, makes use of functional dye extrusion by ABC drug transporters, which
identifies a distinct population of fluorescence-dim cells commonly referred to
as side population (SP). SP cancer cells exhibit canonical stem cell
characteristics and can be abrogated and functionally confirmed using agents that
inhibit the dye-extruding drug transporter (most frequently ABCB1/P
glycoprotein/MDR1/CD243 and ABCG2/Bcrp1/CD338). Moreover, the SP assay is
compatible with other flow cytometric evaluations such as staining of surface
antigens, aldehyde dehydrogenase detection and dead cell discrimination (e.g.,
with 7-AAD or propidium iodide (PI)). Thus, we describe a valuable and broadly
applicable method for CSC identification, isolation and sub-characterization
mechanistically based on a functional, rather than a phenotypic parameter.
Although originally performed with Hoechst 33342 as triggering dye, we here focus
on the more recent Violet dye-based SP phenotype that is resolvable on any flow
cytometer equipped with a violet laser source.
PMID- 28518119
TI - Analysis of Cell Suspensions Isolated from Solid Tissues by Spectral Flow
Cytometry.
AB - Flow cytometry has been used for the past 40 years to define and analyze the
phenotype of lymphoid and other hematopoietic cells. Initially restricted to the
analysis of a few fluorochromes, currently there are dozens of different
fluorescent dyes, and up to 14-18 different dyes can be combined at a time.
However, several limitations still impair the analytical capabilities. Because of
the multiplicity of fluorescent probes, data analysis has become increasingly
complex due to the need of large, multi-parametric compensation matrices.
Moreover, mutant mouse models carrying fluorescent proteins to detect and trace
specific cell types in different tissues have become available, so the analysis
(by flow cytometry) of auto-fluorescent cell suspensions obtained from solid
organs is required. Spectral flow cytometry, which distinguishes the shapes of
emission spectra along a wide range of continuous wavelengths, addresses some of
these problems. The data is analyzed with an algorithm that replaces compensation
matrices and treats auto-fluorescence as an independent parameter. Thus, spectral
flow cytometry should be capable of discriminating fluorochromes with similar
emission peaks and can provide a multi-parametric analysis without compensation
requirements. This protocol describes the spectral flow cytometry analysis,
allowing for a 21-parameter (19 fluorescent probes) characterization and the
management of an auto-fluorescent signal, providing high resolution in minor
population detection. The results presented here show that spectral flow
cytometry presents advantages in the analysis of cell populations from tissues
difficult to characterize in conventional flow cytometry, such as the heart and
the intestine. Spectral flow cytometry thus demonstrates the multi-parametric
analytical capacity of high-performing conventional flow cytometry without the
requirement for compensation and enables auto-fluorescence management.
PMID- 28518120
TI - Ligand Nano-cluster Arrays in a Supported Lipid Bilayer.
AB - Currently there is considerable interest in creating ordered arrays of adhesive
protein islands in a sea of passivated surface for cell biological studies. In
the past years, it has become increasingly clear that living cells respond, not
only to the biochemical nature of the molecules presented to them but also to the
way these molecules are presented. Creating protein micro-patterns is therefore
now standard in many biology laboratories; nano-patterns are also more
accessible. However, in the context of cell-cell interactions, there is a need to
pattern not only proteins but also lipid bilayers. Such dual proteo-lipidic
patterning has so far not been easily accessible. We offer a facile technique to
create protein nano-dots supported on glass and propose a method to backfill the
inter-dot space with a supported lipid bilayer (SLB). From photo-bleaching of
tracer fluorescent lipids included in the SLB, we demonstrate that the bilayer
exhibits considerable in-plane fluidity. Functionalizing the protein dots with
fluorescent groups allows us to image them and to show that they are ordered in a
regular hexagonal lattice. The typical dot size is about 800 nm and the spacing
demonstrated here is 2 microns. These substrates are expected to serve as useful
platforms for cell adhesion, migration and mechano-sensing studies.
PMID- 28518122
TI - Dorsal Root Ganglion Injection and Dorsal Root Crush Injury as a Model for
Sensory Axon Regeneration.
AB - Achieving axon regeneration after nervous system injury is a challenging task. As
different parts of the central nervous system (CNS) differ from each other
anatomically, it is important to identify an appropriate model to use for the
study of axon regeneration. By using a suitable model, we can formulate a
specific treatment based on the severity of injury, the neuronal cell type of
interest, and the desired spinal tract for assessing regeneration. Within the
sensory pathway, DRG neurons are responsible for relaying sensory information
from the periphery to the CNS. We present here a protocol that uses a DRG
injection with a viral vector and a concurrent dorsal root crush injury in the
lower cervical spinal cord of an adult rat as a model to study sensory axon
regeneration. As demonstrated using a control virus, AAV5-GFP, we show the
effectiveness of a direct DRG injection in transducing DRG neurons and tracing
sensory axons into the spinal cord. We also show the effectiveness of the dorsal
root crush injury in denervating the forepaw as an injury model for evaluating
axon regeneration. Despite the requirement for specialized training to perform
this invasive surgical procedure, the protocol is flexible, and potential users
can modify many parts to accommodate their experimental requirements.
Importantly, it can serve as a foundation for those in search of a suitable
animal model for their studies. We believe that this article will help new users
to learn the procedure in a very efficient and effective manner.
PMID- 28518121
TI - Two Algorithms for High-throughput and Multi-parametric Quantification of
Drosophila Neuromuscular Junction Morphology.
AB - Synaptic morphology is tightly related to synaptic efficacy, and in many cases
morphological synapse defects ultimately lead to synaptic malfunction. The
Drosophila larval neuromuscular junction (NMJ), a well-established model for
glutamatergic synapses, has been extensively studied for decades. Identification
of mutations causing NMJ morphological defects revealed a repertoire of genes
that regulate synapse development and function. Many of these were identified in
large-scale studies that focused on qualitative approaches to detect
morphological abnormalities of the Drosophila NMJ. A drawback of qualitative
analyses is that many subtle players contributing to NMJ morphology likely remain
unnoticed. Whereas quantitative analyses are required to detect the subtler
morphological differences, such analyses are not yet commonly performed because
they are laborious. This protocol describes in detail two image analysis
algorithms "Drosophila NMJ Morphometrics" and "Drosophila NMJ Bouton
Morphometrics", available as Fiji-compatible macros, for quantitative, accurate
and objective morphometric analysis of the Drosophila NMJ. This methodology is
developed to analyze NMJ terminals immunolabeled with the commonly used markers
Dlg-1 and Brp. Additionally, its wider application to other markers such as Hrp,
Csp and Syt is presented in this protocol. The macros are able to assess nine
morphological NMJ features: NMJ area, NMJ perimeter, number of boutons, NMJ
length, NMJ longest branch length, number of islands, number of branches, number
of branching points and number of active zones in the NMJ terminal.
PMID- 28518123
TI - Expression of Exogenous Cytokine in Patient-derived Xenografts via Injection with
a Cytokine-transduced Stromal Cell Line.
AB - Patient-derived xenograft (PDX) mice are produced by transplanting human cells
into immune deficient mice. These models are an important tool for studying the
mechanisms of normal and malignant hematopoiesis and are the gold standard for
identifying effective chemotherapies for many malignancies. PDX models are
possible because many of the mouse cytokines also act on human cells. However,
this is not the case for all cytokines, including many that are critical for
studying normal and malignant hematopoiesis in human cells. Techniques that
engineer mice to produce human cytokines (transgenic and knock-in models) require
significant expense before the usefulness of the model has been demonstrated.
Other techniques are labor intensive (injection of recombinant cytokine or
lentivirus) and in some cases require high levels of technical expertise
(hydrodynamic injection of DNA). This report describes a simple method for
generating PDX mice that have exogenous human cytokine (TSLP, thymic stromal
lymphopoietin) via weekly intraperitoneal injection of stroma that have been
transduced to overexpress this cytokine. Use of this method provides an in vivo
source of continuous cytokine production that achieves physiological levels of
circulating human cytokine in the mouse. Plasma levels of human cytokine can be
varied based on the number of stromal cells injected, and cytokine production can
be initiated at any point in the experiment. This method also includes cytokine
negative control mice that are similarly produced, but through intraperitoneal
injection of stroma transduced with a control vector. We have previously
demonstrated that leukemia cells harvested from TSLP-expressing PDX, as compared
to control PDX, exhibit a gene expression pattern more like the original patient
sample. Together the cytokine-producing and cytokine-negative PDX mice produced
by this method provide a model system that we have used successfully to study the
role of TSLP in normal and malignant hematopoiesis.
PMID- 28518124
TI - Direct Re-implantation of Left Coronary Artery into the Aorta in Adults with
Anomalous Origin of Left Coronary Artery from the Pulmonary Artery (ALCAPA).
AB - Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA)
is a rare congenital anomaly which is one of leading causes of myocardial
ischemia and infarction in children. If left untreated, it results in a 90%
mortality rate in the first year of life. In patients who survive to the
adulthood, the coronary steal phenomenon and retrograde left-sided coronary flow
provide a substrate for chronic subendocardial ischemia, which may lead to left
ventricular dysfunction, ischemic mitral regurgitation, malignant ventricular
arrhythmias, and sudden cardiac death. The average age of life-threatening
presentation is 33 years and of sudden cardiac death 31 years. Therefore,
surgical correction is highly recommended as soon as the diagnosis is made,
regardless of age. In adult-type ALCAPA originating from the right-facing sinus
of the pulmonary artery, direct re-implantation of the ALCAPA into the aorta is
the more physiologically sound repair technique to re-establish the dual-coronary
perfusion system and is recommended. This protocol describes the technique of
direct re-implantation of adult-type ALCAPA into the aorta.
PMID- 28518125
TI - Glycoproteomics of the Extracellular Matrix: A Method for Intact Glycopeptide
Analysis Using Mass Spectrometry.
AB - Fibrosis is a hallmark of many cardiovascular diseases and is associated with the
exacerbated secretion and deposition of the extracellular matrix (ECM). Using
proteomics, we have previously identified more than 150 ECM and ECM-associated
proteins in cardiovascular tissues. Notably, many ECM proteins are glycosylated.
This post-translational modification affects protein folding, solubility,
binding, and degradation. We have developed a sequential extraction and
enrichment method for ECM proteins that is compatible with the subsequent liquid
chromatography tandem mass spectrometry (LC-MS/MS) analysis of intact
glycopeptides. The strategy is based on sequential incubations with NaCl, SDS for
tissue decellularization, and guanidine hydrochloride for the solubilization of
ECM proteins. Recent advances in LC-MS/MS include fragmentation methods, such as
combinations of higher-energy collision dissociation (HCD) and electron transfer
dissociation (ETD), which allow for the direct compositional analysis of
glycopeptides of ECM proteins. In the present paper, we describe a method to
prepare the ECM from tissue samples. The method not only allows for protein
profiling but also the assessment and characterization of glycosylation by MS
analysis.
PMID- 28518126
TI - Techniques to Induce and Quantify Cellular Senescence.
AB - In response to cellular stress or damage, proliferating cells can induce a
specific program that initiates a state of long-term cell-cycle arrest, termed
cellular senescence. Accumulation of senescent cells occurs with organismal aging
and through continual culturing in vitro. Senescent cells influence many
biological processes, including embryonic development, tissue repair and
regeneration, tumor suppression, and aging. Hallmarks of senescent cells include,
but are not limited to, increased senescence-associated beta-galactosidase
activity (SA-beta-gal); p16INK4A, p53, and p21 levels; higher levels of DNA
damage, including gamma-H2AX; the formation of Senescence-associated
Heterochromatin Foci (SAHF); and the acquisition of a Senescence-associated
Secretory Phenotype (SASP), a phenomenon characterized by the secretion of a
number of pro-inflammatory cytokines and signaling molecules. Here, we describe
protocols for both replicative and DNA damage-induced senescence in cultured
cells. In addition, we highlight techniques to monitor the senescent phenotype
using several senescence-associated markers, including SA-beta-gal, gamma-H2AX
and SAHF staining, and to quantify protein and mRNA levels of cell cycle
regulators and SASP factors. These methods can be applied to the assessment of
senescence in various models and tissues.
PMID- 28518127
TI - Plunge Freezing: A Tool for the Ultrastructural and Immunolocalization Studies of
Suspension Cells in Transmission Electron Microscopy.
AB - Transmission Electron Microscopy (TEM) is an extraordinary tool for studying cell
ultrastructure, in order to localize proteins and visualize macromolecular
complexes at very high resolution. However, to get as close as possible to the
native state, perfect sample preservation is required. Conventional electron
microscopy (EM) fixation with aldehydes, for instance, does not provide good
ultrastructural preservation. The slow penetration of fixatives induces cell
reorganization and loss of various cell components. Therefore, conventional EM
fixation does not allow for an instantaneous stabilization and preservation of
structures and antigenicity. The best choice for examining intracellular events
is to use cryofixation followed by the freeze-substitution fixation method that
keeps cells in their native state. High-pressure freezing/freeze-substitution,
which preserves the integrity of cellular ultrastructure, is the most commonly
used method, but requires expensive equipment. Here, an easy-to-use and low-cost
freeze fixation method followed by freeze-substitution for suspension cell
cultures is presented.
PMID- 28518128
TI - An In Vitro Caseum Binding Assay that Predicts Drug Penetration in Tuberculosis
Lesions.
AB - The eradication of tuberculosis disease requires drug regimens that can penetrate
the multiple layers of complex pulmonary lesions. Drug distribution in the
caseous cores of cavities and lesions is especially crucial because they harbor
subpopulations of drug-tolerant bacteria also commonly referred to as persisters.
Existing methods for the measurement of drug penetration in tuberculosis lesions
involve costly and time-consuming in vivo pharmacokinetic studies coupled to
bioanalytical or imaging techniques. The in vitro measurement of drug binding to
caseum macromolecules was proposed as an alternative to such techniques since
this binding hinders the passive diffusion of drug molecules through caseum.
Rapid equilibrium dialysis is a fast and reliable system for performing plasma
protein and tissue binding studies. In this protocol, we used a rapid equilibrium
dialysis (RED) device to measure drug binding to homogenates of caseum that is
excised from the lesions and cavities of tuberculosis-infected rabbits. The
protocol also describes how to generate a surrogate matrix from lipid loaded THP
1 macrophages to use in place of caseum. This caseum/surrogate binding assay is
an important tool in tuberculosis drug discovery and can be adapted to help study
drug distribution in lesions or abscesses caused by other diseases.
PMID- 28518129
TI - Cardiac Muscle Cell-based Actuator and Self-stabilizing Biorobot - Part 2.
AB - In recent years, hybrid devices that consist of a living cell or tissue component
integrated with a synthetic mechanical backbone have been developed. These
devices, called biorobots, are powered solely by the force generated from the
contractile activity of the living component and, due to their many inherent
advantages, could be an alternative to conventional fully artificial robots.
Here, we describe the methods to seed and characterize a biological actuator and
a biorobot that was designed, fabricated, and functionalized in the first part of
this two-part article. Fabricated biological actuator and biorobot devices
composed of a polydimethylsiloxane (PDMS) base and a thin film cantilever were
functionalized for cell attachment with fibronectin. Following functionalization,
neonatal rat cardiomyocytes were seeded onto the PDMS cantilever arm at a high
density, resulting in a confluent cell sheet. The devices were imaged every day
and the movement of the cantilever arms was analyzed. On the second day after
seeding, we observed the bending of the cantilever arms due to the forces exerted
by the cells during spontaneous contractions. Upon quantitative analysis of the
cantilever bending, a gradual increase in the surface stress exerted by the cells
as they matured over time was observed. Likewise, we observed movement of the
biorobot due to the actuation of the PDMS cantilever arm, which acted as a fin.
Upon quantification of the swimming profiles of the devices, various propulsion
modes were observed, which were influenced by the resting angle of the fin. The
direction of motion and the beating frequency were also determined by the resting
angle of the fin, and a maximum swim velocity of 142 um/s was observed. In this
manuscript, we describe the procedure for populating the fabricated devices with
cardiomyocytes, as well as for the assessment of the biological actuator and
biorobot activity.
PMID- 28518130
TI - How to Conduct and Interpret Systematic Reviews and Meta-Analyses.
AB - Systematic reviews with or without meta-analyses serve a key purpose in
critically and objectively synthesizing all available evidence regarding a
focused clinical question and can inform clinical practice and clinical
guidelines. Performing a rigorous systematic review is multi-step process, which
includes (a) identifying a well-defined focused clinically relevant question, (b)
developing a detailed review protocol with strict inclusion and exclusion
criteria, (c) systematic literature search of multiple databases and unpublished
data, in consultation with a medical librarian, (d) meticulous study
identification and (e) systematic data abstraction, by at least two sets of
investigators independently, (f) risk of bias assessment, and (g) thoughtful
quantitative synthesis through meta-analysis where relevant. Besides informing
guidelines, credible systematic reviews and quality of evidence assessment can
help identify key knowledge gaps for future studies.
PMID- 28518133
TI - An evaluation of hydrocortisone dosing for neonatal refractory hypotension.
AB - OBJECTIVE: The objective of the study was to compare blood pressure, vasoactive
medication requirements and adverse outcomes after administration of high- versus
low-dose hydrocortisone (HC) in preterm infants. STUDY DESIGN: This is a
retrospective analysis of 106 infants ?28 weeks gestational age with hypotension
requiring vasoactive infusions and high-dose (4 mg kg-1 per day, n=50), low-dose
(1 to 3 mg kg-1 per day, n=20) or no HC (n=36) from 2011 to 2015. Groups were
compared by two-tailed t-test or chi2, and correlation estimated by multivariable
logistic regression. RESULTS: There were no differences in measured efficacy
between the low- and high-dose groups. Infants with pre-treatment cortisol >15
mcg dl-1 who received HC therapy showed less improvement in vasoactive burden,
increased hyperglycemia (P=0.015) and increased death independent of HC dose
(odds ratio 26.3, 3.5 to 198.3, P=0.002). CONCLUSION: These results support using
the lowest effective HC dose in preterm infants. In addition, HC therapy should
likely be avoided in infants who are not cortisol deficient.
PMID- 28518131
TI - Incidence of respiratory viral infection in infants with respiratory symptoms
evaluated for late-onset sepsis.
AB - OBJECTIVE: To determine the frequency, etiology and impact of respiratory viral
infection (RVI) on infants evaluated for late-onset sepsis (LOS), defined as
sepsis occurring >72 h of life, in the neonatal intensive care unit. STUDY
DESIGN: Prospective observational study conducted from 6 March 2014 to 3 May 2016
on infants evaluated for LOS. PCR viral panel performed on nasopharyngeal
specimens among infants with clinical suspicion for RVI. Sequence analysis was
performed to determine viral subtypes. Fisher's exact or chi2 tests were done to
determine the impact of RVI. RESULTS: During the 26-month study, there were 357
blood cultures obtained for LOS evaluations, 29 (8%) had a respiratory virus
detected. Only 88 (25%) of infants evaluated for LOS also had clinical suspicion
for a respiratory viral infection. RSV (14 of 29; 48%) was the predominant virus
detected. Almost all infants (13 of 14; 93%) with RSV required increased
respiratory support. Antimicrobial therapy was withheld or discontinued on most
infants with a virus detected (18 of 29; 62%) and in the majority where there was
no confirmed bacterial co-infection (18 of 20; 90%). CONCLUSION: The incidence of
RVI in infants being evaluated for LOS is about 8%. RVI should be considered in
LOS evaluation to prevent unnecessary antibiotic therapy.
PMID- 28518132
TI - Mind the gap: can videolaryngoscopy bridge the competency gap in neonatal
endotracheal intubation among pediatric trainees? a randomized controlled study.
AB - BACKGROUND: To study the impact of videolaryngoscopy (VL) on intubation success
among pediatric trainees compared with direct laryngoscopy (DL). METHODS: One
hundred pediatric residents were enrolled in a randomized, crossover, simulation
study comparing VL to DL. Following a didactic session on neonatal intubation,
residents intubated a standard neonatal mannequin. Three Neonatal Resuscitation
Program (NRP) scenarios were then conducted, followed by a mannequin intubation
with the alternate device. Number of attempts and time to intubation were
recorded for all intubations. RESULTS: Proportion of successful intubations on
first attempt was greater with VL compared with DL (88% versus 63%; P=0.008). The
DL group increased success after crossover with VL (63% versus 89%; P=0.008).
Exposure to VL also reduced intubation time after device crossover (median
intubation time: 31 versus 17 s; P=0.048). CONCLUSIONS: VL increased the success
of endotracheal intubation by pediatric residents in simulation, with skills
transferrable to DL.
PMID- 28518136
TI - Corrigendum: Intraventricular injections of mesenchymal stem cells activate
endogenous functional remyelination in a chronic demyelinating murine model.
AB - This corrects the article DOI: 10.1038/cddis.2016.130.
PMID- 28518134
TI - ASIC1 and ASIC3 contribute to acidity-induced EMT of pancreatic cancer through
activating Ca2+/RhoA pathway.
AB - Extracellular acid can have important effects on cancer cells. Acid-sensing ion
channels (ASICs), which emerged as key receptors for extracellular acidic pH, are
differently expressed during various diseases and have been implicated in
underlying pathogenesis. This study reports that ASIC1 and ASIC3 are mainly
expressed on membrane of pancreatic cancer cells and upregulated in pancreatic
cancer tissues. ASIC1 and ASIC3 are responsible for an acidity-induced inward
current, which is required for elevation of intracellular Ca2+ concentration
([Ca2+]i). Inhibition of ASIC1 and ASIC3 with siRNA or pharmacological inhibitor
significantly decreased [Ca2+]i and its downstream RhoA during acidity and, thus,
suppressed acidity-induced epithelial-mesenchymal transition (EMT) of pancreatic
cancer cells. Meanwhile, downregulating [Ca2+]i with calcium chelating agent
BAPTA-AM or knockdown of RhoA with siRNA also significantly repressed acidity
induced EMT of pancreatic cancer cells. Significantly, although without obvious
effect on proliferation, knockdown of ASIC1 and ASIC3 in pancreatic cancer cells
significantly suppresses liver and lung metastasis in xenograft model. In
addition, ASIC1 and ASIC3 are positively correlated with expression of
mesenchymal marker vimentin, but inversely correlated with epithelial marker E
cadherin in pancreatic cancer cells. In conclusion, this study indicates that
ASICs are master regulator of acidity-induced EMT. In addition, the data
demonstrate a functional link between ASICs and [Ca2+]i/RhoA pathway, which
contributes to the acidity-induced EMT.
PMID- 28518135
TI - RACK1 depletion in the ribosome induces selective translation for non-canonical
autophagy.
AB - RACK1, which was first demonstrated as a substrate of PKCbeta II, functions as a
scaffold protein and associates with the 40S small ribosomal subunit. According
to previous reports, ribosomal RACK1 was also suggested to control translation
depending on the status in translating ribosome. We here show that RACK1
knockdown induces autophagy independent of upstream canonical factors such as
Beclin1, Atg7 and Atg5/12 conjugates. We further report that RACK1 knockdown
induces the association of mRNAs of LC3 and Bcl-xL with polysomes, indicating
increased translation of these proteins. Therefore, we propose that the RACK1
depletion-induced autophagy is distinct from canonical autophagy. Finally, we
confirm that cells expressing mutant RACK1 (RACK1R36D/K38E) defective in ribosome
binding showed the same result as RACK1-knockdown cells. Altogether, our data
clearly show that the depletion of ribosomal RACK1 alters the capacity of the
ribosome to translate specific mRNAs, resulting in selective translation of mRNAs
of genes for non-canonical autophagy induction.
PMID- 28518138
TI - Betulin exhibits anti-inflammatory activity in LPS-stimulated macrophages and
endotoxin-shocked mice through an AMPK/AKT/Nrf2-dependent mechanism.
AB - Continued oxidative stress can lead to chronic inflammation, which in turn could
mediate most chronic diseases including cancer. Nuclear factor erythroid 2
related factor (Nrf2), a critical transcriptional activator for antioxidative
responses, has envolved to be an attractive drug target for the treatment or
prevention of human diseases. In the present study, we investigated the effects
and mechanisms of betulin on Nrf2 activation and its involvement in the
lipopolysaccharide (LPS)-triggered inflammatory system. In macrophages, betulin
activated the Nrf2 signaling pathway and increased Nrf2-targeted antioxidant and
detoxifying enzymes, including NADPH, quinine oxidoreductase 1 (NQO1), heme
oxygenase-1 (HO-1), gamma-glutamyl cysteine synthetase catalytic subunit (GCLC)
and modifier subunit (GCLM) in a dose and time dependent manner. Importantly, we
found betulin-induced activation of Nrf2 is AMPK/AKT/GSK3beta dependent, as
pharmacologically inactivating AMPK blocked the activating effect of betulin on
AKT, GSK3beta and Nrf2. Furthermore, betulin attenuated LPS-induced inflammatory
mediators (iNOS and COX-2) and MAPK inflammatory signaling pathway. The effect of
betulin on HO-1 and NQO1 upregulation, iNOS and COX-2 the downregulation, and
survival time extension was largely weakened when Nrf2 was depleted in vitro and
in vivo. Our results demonstrate that the AMPK/AKT/Nrf2 pathways are essential
for the anti-inflammatory effects of betulin in LPS-stimulated macrophages and
endotoxin-shocked mice.
PMID- 28518137
TI - Nerve growth factor from Chinese cobra venom stimulates chondrogenic
differentiation of mesenchymal stem cells.
AB - Growth factors such as transforming growth factor beta1 (TGF-beta1), have
critical roles in the regulation of the chondrogenic differentiation of
mesenchymal stem cells (MSCs), which promote cartilage repair. However, the
clinical applications of the traditional growth factors are limited by their high
cost, functional heterogeneity and unpredictable effects, such as cyst formation.
It may be advantageous for cartilage regeneration to identify a low-cost
substitute with greater chondral specificity and easy accessibility. As a
neuropeptide, nerve growth factor (NGF) was involved in cartilage metabolism and
NGF is hypothesized to mediate the chondrogenic differentiation of MSCs. We
isolated NGF from Chinese cobra venom using a three-step procedure that we had
improved upon from previous studies, and investigated the chondrogenic potential
of NGF on bone marrow MSCs (BMSCs) both in vitro and in vivo. The results showed
that NGF greatly upregulated the expression of cartilage-specific markers. When
applied to cartilage repair for 4, 8 and 12 weeks, NGF-treated BMSCs have greater
therapeutic effect than untreated BMSCs. Although inferior to TGF-beta1 regarding
its chondrogenic potential, NGF showed considerably lower expression of collagen
type I, which is a fibrocartilage marker, and RUNX2, which is critical for
terminal chondrocyte differentiation than TGF-beta1, indicating its chondral
specificity. Interestingly, NGF rarely induced BMSCs to differentiate into a
neuronal phenotype, which may be due to the presence of other chondrogenic
supplements. Furthermore, the underlying mechanism revealed that NGF-mediated
chondrogenesis may be associated with the activation of PI3K/AKT and MAPK/ERK
signaling pathways via the specific receptor of NGF, TrkA. In addition, NGF is
easily accessed because of the abundance and low price of cobra venom, as well as
the simplified methods for separation and purification. This study was the first
to demonstrate the chondrogenic potential of NGF, which may provide a reference
for cartilage regeneration in the clinic.
PMID- 28518140
TI - A miRNA-101-3p/Bim axis as a determinant of serum deprivation-induced endothelial
cell apoptosis.
AB - Serum deprivation or withdrawal induces apoptosis in endothelial cells, resulting
in endothelial cell dysfunction that is associated with cardiovascular disease.
However, there is still limited information on the role of miRNA in serum
deprivation-induced apoptosis. Here we found that serum deprivation increased
caspase-dependent apoptosis through miRNA-101-3p downregulation, without altering
expression of its host gene RNA 3'-terminal phosphate cyclase-like 1, which was
highly correlated with suppressed expression levels of Dicer and Argonaute 2
(Ago2), indicating that miR-101-3p is post-transcriptionally elevated in serum
deprived conditions. The decreased miR-101-3p caused elevated Bim expression by
targeting its 3'-untranslated region (3'-UTR). This resulted in activation of the
intrinsic pathway of apoptosis via interaction with Bcl-2, decreased
mitochondrial membrane potential, cytochrome c release, mitochondrial reactive
oxygen species (ROS) production, and caspase activation. These events were
abrogated by miR-101-3p mimic and the proapoptotic Bim siRNA, which suggest a
determinant role of the miR-101-3p/Bim axis in serum deprivation-induced
apoptosis. The apoptosis induced by miR-101-3p-mediated Bim expression is
mediated by both caspase-3 and -1, which are activated by two distinct intrinsic
mechanisms, cytochrome c release and ROS-induced inflammasome activation,
respectively. In other words, the antioxidant inhibited endothelial cell death
mediated by caspase-1 that activated caspase-7, but not caspase-3. These findings
provide mechanistic insight into a novel function of miR-101-3p in serum
withdrawal-induced apoptosis triggered by activating two different intrinsic or
mitochondrial apoptosis pathways, implicating miR-101-3p as a therapeutic target
that limits endothelial cell death associated with vascular disorders.
PMID- 28518139
TI - MiR-106b and miR-93 regulate cell progression by suppression of PTEN via PI3K/Akt
pathway in breast cancer.
AB - Accumulating evidences have revealed that dysregulated microRNAs (miRNAs) involve
in the tumorigenesis, progression and even lead to poor prognosis of various
carcinomas, including breast cancer. MiRNA-106b-5p (miR-106b) and miRNA-93-5p
(miR-93) levels were confirmed to be significantly upregulated in breast cancer
clinical samples (n=36) and metastatic cell line (MDA-MB-231) compared with those
in the paired adjacent tissues and normal breast epithelial cell line (MCF-10A).
Moreover, further research stated that the capability of migration, invasion and
proliferation changed along with the altered expression of miR-106b and miR-93 in
breast cancer. PTEN, the tumor-suppressor gene, was discovered to be reduced in
breast cancer tissues or MDA-MB-231 cells with high levels of miR-106b and miR
93, which were inversely expressed in PTEN overexpression tissues or cells. Based
on the investigation, miR-106b and miR-93 induced the migration, invasion and
proliferation and simultaneously enhanced the activity of phosphatidylinositol-3
kinase (PI3K)/Akt pathway of MCF-7 cells, which could be blocked by upregulation
of PTEN. Furthermore, suppression of PTEN reversed the function induced by anti
miR-106b and anti-miR-93 in MDA-MB-231 cells, indicating that PTEN was directly
targeted by these miRNAs and acted as the potential therapeutic target for breast
cancer therapy. In short, reductive PTEN mediated by miR-106b and miR-93 promoted
cell progression through PI3K/Akt pathway in breast cancer.
PMID- 28518141
TI - CAF-secreted CXCL1 conferred radioresistance by regulating DNA damage response in
a ROS-dependent manner in esophageal squamous cell carcinoma.
AB - Five-year survival rate of esophageal squamous cell carcinoma (ESCC) patients
treated with radiotherapy is <20%. Our study aimed to investigate whether cancer
associated fibroblasts (CAFs), one major component of tumor microenvironment,
were involved in tumor radioresistance in ESCC. By use of human
chemokine/cytokine array, human chemokine CXCL1 was found to be highly expressed
in CAFs compared with that in matched normal fibroblasts. Inhibition of CXCL1
expression in CAFs significantly reversed CAF-conferred radioresistance in vitro
and in vivo. CAF-secreted CXCL1 inhibited the expression of reactive oxygen
species (ROS)-scavenging enzyme superoxide dismutase 1, leading to increased ROS
accumulation following radiation, by which DNA damage repair was enhanced and the
radioresistance was mediated. CAF-secreted CXCL1 mediated the radioresistance
also by activation of Mek/Erk pathway. The cross talk of CAFs and ESCC cells
induced CXCL1 expression in an autocrine/paracrine signaling loop, which further
enhanced tumor radioresistance. Together, our study highlighted CAF-secreted
CXCL1 as an attractive target to reverse tumor radioresistance and can be used as
an independent prognostic factor of ESCC patients treated with chemoradiotherapy.
PMID- 28518142
TI - MiR-130a-3p attenuates activation and induces apoptosis of hepatic stellate cells
in nonalcoholic fibrosing steatohepatitis by directly targeting TGFBR1 and
TGFBR2.
AB - Nonalcoholic fibrosing steatohepatitis is a uniform process that occurs
throughout nonalcoholic fatty liver disease (NAFLD). MicroRNAs (miRNAs) have been
shown to be involved in the biological processes, but the role and molecular
mechanism of miRNAs in NAFLD are not entirely clear. In this study, we observed a
significant reduction in the expression of miR-130a-3p in livers of a mouse model
with fibrosis induced by a methionine-choline-deficient diet, of NAFLD patients,
and in activated hepatic stellate cells (HSCs). A dual-luciferase activity assay
confirmed that transforming growth factor-beta receptors (TGFBRs) 1 and 2 were
both the target genes of miR-130a-3p. The hepatic expression of TGFBR1 and TGFBR2
was significantly increased. Moreover, the overexpression of miR-130a-3p in HSCs
inhibited HSC activation and proliferation, concomitant with the decreased
expression of TGFBR1, TGFBR2, Smad2, Smad3, matrix metalloproteinase-2 (MMP-2),
MMP-9, type I collagen (Col-1), and Col-4. In addition, the overexpression of miR
130a-3p promoted HSC apoptosis by inducing the expression of caspase-dependent
apoptosis genes. Transfection with si-TGFBR1 and si-TGFBR2 revealed effects on
HSC function that were consistent with those of miR-130a-3p. TGFBR1 and TGFBR2
rescued the miR-130a-3p-mediated reductions in the mRNA and protein expression
levels of Smad2, Smad3, Col-1, and Col-4. In conclusion, our findings suggest
that miR-130a-3p might play a critical role in negatively regulating HSC
activation and proliferation in the progression of nonalcoholic fibrosing
steatohepatitis by directly targeting TGFBR1 and TGFBR2 via the TGF-beta/SMAD
signaling pathway.
PMID- 28518143
TI - Calcium sensing receptor protects high glucose-induced energy metabolism disorder
via blocking gp78-ubiquitin proteasome pathway.
AB - Diabetic cardiomyopathy (DCM) is a major complication and fatal cause of the
patients with diabetes. The calcium sensing receptor (CaSR) is a G protein
coupled receptor, which is involved in maintaining calcium homeostasis,
regulating cell proliferation and apoptosis, and so on. In our previous study, we
found that CaSR expression, intracellular calcium levels and cardiac function
were all significantly decreased in DCM rats; however, the exact mechanism are
not clear yet. The present study revealed the protective role of CaSR in
myocardial energy metabolism disorder induced by high glucose (HG) as well as the
underlying mechanism. Here, we demonstrated that HG decreased the expression of
CaSR, mitochondrial fusion proteins (Mfn1, Mfn2), cell gap junction related
proteins (Cx43, beta-catenin, N-cadherin), and intracellular ATP concentration.
In contrast, HG increased extracellular ATP concentration, the expression of
gp78, mitochondrial fission proteins (Fis1, Drp1), and the ubiquitination levels
of Mfn1, Mfn2 and Cx43. Moreover, CaSR agonist and gp78-siRNA significantly
reduced the above changes. Taken together, these results suggest that HG induces
myocardial energy metabolism disorder via decrease of CaSR expression, and
activation of gp78-ubiquitin proteasome system. In turn, these effects disrupt
the structure and function of the mitochondria and the cell gap junction, result
in the reduced ATP synthesis and the increased ATP leakage. Stimulation of CaSR
significantly attenuates HG-induced abnormal myocardial energy metabolism,
suggesting CaSR would be a promising potential therapeutic target for DCM.
PMID- 28518144
TI - MicroRNA-23b functions as an oncogene and activates AKT/GSK3beta/beta-catenin
signaling by targeting ST7L in hepatocellular carcinoma.
AB - Hepatocellular carcinoma (HCC) is a malignant tumor and threatens human life
worldwide, whereas the etiology and pathogenesis of HCC have not been fully
determined. In the past few years, many microRNAs (miRNAs) have been proved to
have important roles in tumorigenesis of HCC. In this study, we found that miR
23b was significantly upregulated in tumor tissues of HCC patients. Functional
tests showed that miR-23b could promote HCC cell proliferation and metastasis in
vitro and in vivo. Then, mechanistic investigations suggested that ST7L was a
direct target of miR-23b and involved in the promotion effects of miR-23b on HCC
tumorigenesis and metastasis. Furthermore, our study indicated that ST7L could
interact with the carboxyl terminal region of AKT and suppress AKT/GSK3beta/beta
catenin pathway in HCC cells. In conclusion, our study revealed important roles
of miR-23b and ST7L in progression of HCC.
PMID- 28518146
TI - Acyl-CoA thioesterase 7 is involved in cell cycle progression via regulation of
PKCzeta-p53-p21 signaling pathway.
AB - Acyl-CoA thioesterase 7 (ACOT7) is a major isoform of the ACOT family that
catalyzes hydrolysis of fatty acyl-CoAs to free fatty acids and CoA-SH. However,
canonical and non-canonical functions of ACOT7 remain to be discovered. In this
study, for the first time, ACOT7 was shown to be responsive to genotoxic stresses
such as ionizing radiation (IR) and the anti-cancer drug doxorubicin in time- and
dose-dependent manners. ACOT7 knockdown induced cytostasis via activation of the
p53-p21 signaling pathway without a DNA damage response. PKCzeta was specifically
involved in ACOT7 depletion-mediated cell cycle arrest as an upstream molecule of
the p53-p21 signaling pathway in MCF7 human breast carcinoma and A549 human lung
carcinoma cells. Of the other members of the ACOT family, including ACOT1, 4, 8,
9, 11, 12, and 13 that were expressed in human, ACOT4, 8, and 12 were responsive
to genotoxic stresses. However, none of those had a role in cytostasis via
activation of the PKCzeta-p53-p21 signaling pathway. Analysis of the ACOT7
prognostic value revealed that low ACOT7 levels prolonged overall survival
periods in breast and lung cancer patients. Furthermore, ACOT7 mRNA levels were
higher in lung cancer patient tissues compared to normal tissues. We also
observed a synergistic effect of ACOT7 depletion in combination with either IR or
doxorubicin on cell proliferation in breast and lung cancer cells. Together, our
data suggest that a low level of ACOT7 may be involved, at least in part, in the
prevention of human breast and lung cancer development via regulation of cell
cycle progression.
PMID- 28518145
TI - Cytoplasmic RAP1 mediates cisplatin resistance of non-small cell lung cancer.
AB - Cytotoxic chemotherapy agents (e.g., cisplatin) are the first-line drugs to treat
non-small cell lung cancer (NSCLC) but NSCLC develops resistance to the agent,
limiting therapeutic efficacy. Despite many approaches to identifying the
underlying mechanism for cisplatin resistance, there remains a lack of effective
targets in the population that resist cisplatin treatment. In this study, we
sought to investigate the role of cytoplasmic RAP1, a previously identified
positive regulator of NF-kappaB signaling, in the development of cisplatin
resistance in NSCLC cells. We found that the expression of cytoplasmic RAP1 was
significantly higher in high-grade NSCLC tissues than in low-grade NSCLC;
compared with a normal pulmonary epithelial cell line, the A549 NSCLC cells
exhibited more cytoplasmic RAP1 expression as well as increased NF-kappaB
activity; cisplatin treatment resulted in a further increase of cytoplasmic RAP1
in A549 cells; overexpression of RAP1 desensitized the A549 cells to cisplatin,
and conversely, RAP1 depletion in the NSCLC cells reduced their proliferation and
increased their sensitivity to cisplatin, indicating that RAP1 is required for
cell growth and has a key mediating role in the development of cisplatin
resistance in NSCLC cells. The RAP1-mediated cisplatin resistance was associated
with the activation of NF-kappaB signaling and the upregulation of the
antiapoptosis factor BCL-2. Intriguingly, in the small portion of RAP1-depleted
cells that survived cisplatin treatment, no induction of NF-kappaB activity and
BCL-2 expression was observed. Furthermore, in established cisplatin-resistant
A549 cells, RAP1 depletion caused BCL2 depletion, caspase activation and dramatic
lethality to the cells. Hence, our results demonstrate that the cytoplasmic RAP1
NF-kappaB-BCL2 axis represents a key pathway to cisplatin resistance in NSCLC
cells, identifying RAP1 as a marker and a potential therapeutic target for
cisplatin resistance of NSCLC.
PMID- 28518147
TI - Survivin, a key player in cancer progression, increases in obesity and protects
adipose tissue stem cells from apoptosis.
AB - Adipose tissue (AT) has a central role in obesity-related metabolic imbalance
through the dysregulated production of cytokines and adipokines. In addition to
its known risk for cardiovascular disease and diabetes, obesity is also a major
risk for cancer. We investigated the impact of obesity for the expression of
survivin, an antiapoptotic protein upregulated by adipokines and a diagnostic
biomarker of tumor onset and recurrence. In a cross-sectional study of 111
subjects classified by body mass index, circulating levels of survivin and gene
expression in subcutaneous AT were significantly higher in obese patients and
positively correlated with leptin. Within AT, survivin was primarily detected in
human adipocyte-derived stem cells (hASCs), the adipocyte precursors that
determine AT expansion. Remarkably, survivin expression was significantly higher
in hASCs isolated from obese patients that from lean controls and was increased
by proinflammatory M1 macrophage soluble factors including IL-1beta. Analysis of
survivin expression in hASCs revealed a complex regulation including epigenetic
modifications and protein stability. Surprisingly, obese hASCs showed survivin
promoter hypermethylation that correlated with a significant decrease in its mRNA
levels. Nonetheless, a lower level of mir-203, which inhibits survivin protein
translation, and higher protein stability, was found in obese hASCs compared with
their lean counterparts. We discovered that survivin levels determine the
susceptibility of hASCs to apoptotic stimuli (including leptin and hypoxia).
Accordingly, hASCs from an obese setting were protected from apoptosis.
Collectively, these data shed new light on the molecular mechanisms governing AT
expansion in obesity through promotion of hASCs that are resistant to apoptosis,
and point to survivin as a potential new molecular player in the communication
between AT and tumor cells. Thus, inhibition of apoptosis targeting survivin
might represent an effective strategy for both obesity and cancer therapy.
PMID- 28518148
TI - Hepatocyte polyploidization and its association with pathophysiological
processes.
AB - A characteristic cellular feature of the mammalian liver is the progressive
polyploidization of the hepatocytes, where individual cells acquire more than two
sets of chromosomes. Polyploidization results from cytokinesis failure that takes
place progressively during the course of postnatal development. The proportion of
polyploidy also increases with the aging process or with cellular stress such as
surgical resection, toxic stimulation, metabolic overload, or oxidative damage,
to involve as much as 90% of the hepatocytes in mice and 40% in humans.
Hepatocyte polyploidization is generally considered an indicator of terminal
differentiation and cellular senescence, and related to the dysfunction of
insulin and p53/p21 signaling pathways. Interestingly, the high prevalence of
hepatocyte polyploidization in the aged mouse liver can be reversed when the
senescent hepatocytes are serially transplanted into young mouse livers. Here we
review the current knowledge on the mechanism of hepatocytes polyploidization
during postnatal growth, aging, and liver diseases. The biologic significance of
polyploidization in senescent reversal, within the context of new ways to think
of liver aging and liver diseases is considered.
PMID- 28518149
TI - Rnf138 deficiency promotes apoptosis of spermatogonia in juvenile male mice.
AB - Spermatogenesis, the process by which haploid sperm cells are produced from a
diploid precursor cell, is essential for sexual reproduction. Here, we report
that RING-finger protein 138 (Rnf138) is highly expressed in testes, especially
in spermatogonia and spermatocytes. The role of Rnf138 in spermatogenesis was
examined using a Rnf138-knockout mouse model. Rnf138 deficiency resulted in
increased apoptosis in spermatogenic cells, loss of proliferative spermatogonia,
delayed development of spermatozoa and impaired fertility. The proportion of
PLZF+Ki67+ cells within the PLZF+ population decreased in the knockout mice. The
phenotype was further assessed by RNA-sequencing (RNA-seq), which determined that
the expression levels of many genes involved in spermatogenesis were altered in
the testis of Rnf138-knockout mice. Thus, Rnf138 deficiency promotes the
apoptosis of spermatogenic cells, which may have been caused by the aberrant
proliferation of spermatogonia in mouse testis development.
PMID- 28518150
TI - Cycloheximide promotes paraptosis induced by inhibition of cyclophilins in
glioblastoma multiforme.
AB - Cancer is the second leading cause of death worldwide. Current treatment
strategies based on multi-agent chemotherapy and/or radiation regimens have
improved overall survival in some cases. However, resistance to apoptosis often
develops in cancer cells, and its occurrence is thought to contribute to
treatment failure. Non-apoptotic cell death mechanisms have become of great
interest, therefore, in hopes that they would bypass tumor cell resistance.
Glioblastoma multiforme (GBM), a grade IV astrocytic tumor is the most frequent
brain tumor in adults, and has a high rate of mortality. We report that NIM811, a
small molecule cyclophilin-binding inhibitor, induces catastrophic vacuolization
and cell death in GBM cells. These unique features are distinct from many known
cell death pathways, and are associated with an incompletely defined cell death
mechanism known as paraptosis. We found that NIM811-induced paraptosis is due to
unresolved ER stress. The abnormal upregulation of protein translation was
responsible for the build-up of misfolded or unfolded proteins in ER, whereas pro
survival autophagy and UPR signals were shutdown during prolonged treatment with
NIM811. Although cycloheximide has been claimed to suppress paraptosis, instead
we find that it only temporarily delayed vacuole formation, but actually enhanced
paraptotic cell death in the long term. On the other hand, mTOR inhibitors
rescued cells from NIM811-induced paraptosis by sustaining autophagy and the UPR,
while specifically restraining cap-dependent translation. These findings not only
provide new insights into the mechanisms underlying paraptosis, but also shed
light on a potential approach to enhance GBM treatment.
PMID- 28518153
TI - Enchained growth.
PMID- 28518152
TI - STAT5 alters the state of transcriptional networks, driving aggressive leukemia.
PMID- 28518151
TI - Disulfiram/copper selectively eradicates AML leukemia stem cells in vitro and in
vivo by simultaneous induction of ROS-JNK and inhibition of NF-kappaB and Nrf2.
AB - Acute myeloid leukemia (AML) is a heterogeneous malignancy. Despite the advances
in past decades, the clinical outcomes of AML patients remain poor. Leukemia stem
cells (LSCs) is the major cause of the recurrence of AML even after aggressive
treatment making, promoting development of LSC-targeted agents is an urgent
clinical need. Although the antitumor activity of disulfiram (DS), an approved
anti-alcoholism drug, has been demonstrated in multiple types of tumors including
hematological malignancies such as AML, it remains unknown whether this agent
would also be able to target cancer stem cells like LSCs. Here, we report the in
vitro and in vivo activity of DS in combination with copper (Cu) against
CD34+/CD38+ leukemia stem-like cells sorted from KG1alpha and Kasumi-1 AML cell
lines, as well as primary CD34+ AML samples. DS plus Cu (DS/Cu) displayed marked
inhibition of proliferation, induction of apoptosis, and suppression of colony
formation in cultured AML cells while sparing the normal counterparts. DS/Cu also
significantly inhibited the growth of human CD34+/CD38+ leukemic cell-derived
xenografts in NOD/SCID mice. Mechanistically, DS/Cu-induced cytotoxicity was
closely associated with activation of the stress-related ROS-JNK pathway as well
as simultaneous inactivation of the pro-survival Nrf2 and nuclear factor-kappaB
pathways. In summary, our findings indicate that DS/Cu selectively targets
leukemia stem-like cells both in vitro and in vivo, thus suggesting a promising
LSC-targeted activity of this repurposed agent for treatment of relapsed and
refractory AML.
PMID- 28518155
TI - Monocyte and DC atlas.
PMID- 28518157
TI - Erratum: THEMIS enhances TCR signaling and enables positive selection by
selective inhibition of the phosphatase SHP-1.
PMID- 28518158
TI - Unusual suspects: dancing with stromal cells.
PMID- 28518154
TI - IL-17+ gammadelta T cells as kick-starters of inflammation.
AB - Shortly after the discovery of interleukin 17 (IL-17)-producing CD4+ helper T
cells (TH17 cells), it was found that gammadelta T cells can also secrete large
amounts of this pro-inflammatory cytokine. A decade later, it is now known that
IL-17+ gammadelta T cells (gammadelta17 T cells) are often the main providers of
IL-17A in various models of inflammatory diseases, while they also contribute to
protective immune responses to infectious organisms. Due to an intricate thymic
program of differentiation, gammadelta17 T cells are able to respond faster than
TH17 cells do and thus predominate in the early stages of inflammatory responses.
Here we review the current knowledge of the development, activation and
pathophysiological functions of gammadelta17 T cells, aiming to increase the
awareness in the community of the therapeutic potential of this 'other side' of
IL-17-mediated immune responses.
PMID- 28518160
TI - Superinduction!
PMID- 28518161
TI - Erratum: Epigenetic landscapes reveal transcription factors that regulate CD8+ T
cell differentiation.
PMID- 28518159
TI - Alternative monocytes settle in for the long term.
PMID- 28518156
TI - Interleukin 17 is a chief orchestrator of immunity.
AB - Increased understanding of the biology of interleukin 17 (IL-17) has revealed
that this cytokine is a central player in immunity at the sites most exposed to
microorganisms. Although it has been strongly associated with immunopathology, IL
17 also has an important role in host defense. The regulation of IL-17 secretion
seems to be shared among various cell types, each of which can concomitantly
secrete additional products. IL-17 has only modest activity on its own; its
impact in immunity arises from its synergistic action with other factors, its
self-sustaining feedback loop and, in some cases, its role as a counterpart of
interferon-gamma (IFN-gamma). Together these attributes provide a robust response
against microorganisms, but they can equally contribute to immune pathology. Here
we focus on a discussion of the role of IL-17 during infection.
PMID- 28518162
TI - Zika-neutralizing antibodies.
PMID- 28518163
TI - Exploitation by Mtb.
PMID- 28518164
TI - Fertilization and nucleic acid sensing.
PMID- 28518165
TI - Erratum: CCL19-CCR7-dependent reverse transendothelial migration of myeloid cells
clears Chlamydia muridarum from the arterial intima.
PMID- 28518166
TI - Corrigendum: Quantifying the shifting landscape of B cell immunodominance.
PMID- 28518167
TI - RNA-binding proteins, the guardians of the marginal zone.
PMID- 28518169
TI - Population-based impact of noninvasive prenatal screening on screening and
diagnostic testing for fetal aneuploidy.
AB - PurposeTo assess the population-wide impact of noninvasive prenatal screening
(NIPS) on combined first-trimester screening (CFTS), early ultrasound (11-13
weeks), and invasive prenatal diagnosis in a state with over 73,000 births per
year.MethodsAnalysis of population-based data from 2000 to 2015 including (i)
invasive prenatal tests, (ii) CFTS uptake, and (iii) total births. Utilization of
early ultrasound was analyzed before and after NIPS (2010-2015).ResultsInvasive
testing decreased significantly by 39.6% from 2012 to 2015 despite steady births.
More than half of all confirmed cases of trisomy 21 were ascertained by NIPS in
2015, despite NIPS comprising only 11.7% of total indications for invasive
testing. CFTS uptake declined significantly from 77.5% in 2013 to 68.1% in 2015,
but 11- to 13-week ultrasounds did not. In 2015, ultrasound abnormality replaced
CFTS as the most common indication for invasive testing and chromosomal
microarray was performed for 85.3% of all prenatal karyotypes.ConclusionPrenatal
testing is now unequivocally in the genomic era. NIPS is now the screening test
that precedes the majority of confirmed diagnoses of trisomy 21. The
contributions of NIPS, early ultrasound, and chromosome microarray have led to
unprecedented detection rates of major chromosome abnormalities, now found in 20%
of all invasive tests.
PMID- 28518168
TI - Using high-resolution variant frequencies to empower clinical genome
interpretation.
AB - PurposeWhole-exome and whole-genome sequencing have transformed the discovery of
genetic variants that cause human Mendelian disease, but discriminating
pathogenic from benign variants remains a daunting challenge. Rarity is
recognized as a necessary, although not sufficient, criterion for pathogenicity,
but frequency cutoffs used in Mendelian analysis are often arbitrary and overly
lenient. Recent very large reference datasets, such as the Exome Aggregation
Consortium (ExAC), provide an unprecedented opportunity to obtain robust
frequency estimates even for very rare variants.MethodsWe present a statistical
framework for the frequency-based filtering of candidate disease-causing
variants, accounting for disease prevalence, genetic and allelic heterogeneity,
inheritance mode, penetrance, and sampling variance in reference
datasets.ResultsUsing the example of cardiomyopathy, we show that our approach
reduces by two-thirds the number of candidate variants under consideration in the
average exome, without removing true pathogenic variants (false-positive
rate<0.001).ConclusionWe outline a statistically robust framework for assessing
whether a variant is "too common" to be causative for a Mendelian disorder of
interest. We present precomputed allele frequency cutoffs for all variants in the
ExAC dataset.
PMID- 28518170
TI - Prenatal exome sequencing in anomalous fetuses: new opportunities and challenges.
AB - PurposeWe investigated the diagnostic and clinical performance of exome
sequencing in fetuses with sonographic abnormalities with normal karyotype and
microarray and, in some cases, normal gene-specific sequencing.MethodsExome
sequencing was performed on DNA from 15 anomalous fetuses and from the peripheral
blood of their parents. Parents provided consent to be informed of diagnostic
results in the fetus, medically actionable findings in the parents, and their
identification as carrier couples for significant autosomal recessive conditions.
We assessed the perceptions and understanding of exome sequencing using mixed
methods in 15 mother-father dyads.ResultsIn seven (47%) of 15 fetuses, exome
sequencing provided a diagnosis or possible diagnosis with identification of
variants in the following genes: COL1A1, MUSK, KCTD1, RTTN, TMEM67, PIEZO1 and
DYNC2H1. One additional case revealed a de novo nonsense mutation in a novel
candidate gene (MAP4K4). The perceived likelihood that exome sequencing would
explain the results (5.2 on a 10-point scale) was higher than the approximately
30% diagnostic yield discussed in pretest counseling.ConclusionExome sequencing
had diagnostic utility in a highly select population of fetuses where a genetic
diagnosis was highly suspected. Challenges related to genetics literacy and
variant interpretation must be addressed by highly tailored pre- and posttest
genetic counseling.
PMID- 28518171
TI - FISH-Flow, a protocol for the concurrent detection of mRNA and protein in single
cells using fluorescence in situ hybridization and flow cytometry.
AB - We describe a flow-cytometry-based protocol for intracellular mRNA measurements
in nonadherent mammalian cells using fluorescence in situ hybridization (FISH)
probes. The method, which we call FISH-Flow, allows for high-throughput
multiparametric measurements of gene expression, a task that was not feasible
with earlier, microscopy-based approaches. The FISH-Flow protocol involves cell
fixation, permeabilization and hybridization with a set of fluorescently labeled
oligonucleotide probes. In this protocol, surface and intracellular protein
markers can also be stained with fluorescently labeled antibodies for
simultaneous protein and mRNA measurement. Moreover, a semiautomated, single-tube
version of the protocol can be performed with a commercially available cell-wash
device that reduces cell loss, operator time and interoperator variability. It
takes ~30 h to perform this protocol. An example of FISH-Flow measurements of
cytokine mRNA induction by ex vivo stimulation of primed T cells with specific
antigens is described.
PMID- 28518174
TI - Cardiac resuscitation: Benefit of bystander CPR and defibrillation.
PMID- 28518173
TI - Simultaneous quantification of N- and O-glycans using a solid-phase method.
AB - Glycosylation has a pivotal role in a diverse range of biological activities,
modulating the structure and function of proteins. Glycogens coupled to the
nitrogen atom (N-linked) of asparagine side chains or to the oxygen atom (O
linked) of serine and threonine side chains represent the two major protein
glycosylation forms. N-glycans can be released by glycosidases, whereas O-glycans
are often cleaved by chemical reaction. However, it is challenging to combine
these enzymatic and chemical reactions in order to analyze both N- and O-glycans.
We recently developed a glycoprotei n immobilization for glycan extraction (GIG)
method that allows for the simultaneous analysis of N- and O-glycans on a solid
support. GIG enables quantitative analysis of N-glycans and O-glycans from a
single specimen and can be applied to a high-throughput automated platform. Here
we provide a step-by-step GIG protocol that includes procedures for (i) protein
immobilization on an aldehyde-active solid support by reductive amination; (ii)
stabilization of fragile sialic acids by carbodiimide coupling; (iii) release of
N-glycans by PNGase F digestion; (iv) release of O-glycans by beta-elimination
using ammonia in the presence of 1-phenyl-3-methyl-5-pyrazolone (PMP) to prevent
alditol peeling from O-glycans; (v) mass spectrometry (MS) analysis; and (vi)
data analysis for identification of glycans using in-house developed software
(GIG Tool; free to download via http://www.biomarkercenter.org/gigtool). The GIG
tool extracts precursor masses, oxonium ions and glycan fragments from tandem
(liquid chromatography (LC)-MS/MS) mass spectra for glycan identification, and
reporter ions from quaternary amine containing isobaric tag for glycan (QUANTITY)
isobaric tags are used for quantification of the relative abundance of N-glycans.
The GIG protocol takes ~3 d.
PMID- 28518175
TI - Dyslipidaemia: HDL-related biomarkers of cardiovascular risk.
PMID- 28518177
TI - Genetics: Smoking reduces genetic protection against CHD.
PMID- 28518172
TI - Super-resolution microscopy with DNA-PAINT.
AB - Super-resolution techniques have begun to transform biological and biomedical
research by allowing researchers to observe structures well below the classic
diffraction limit of light. DNA points accumulation for imaging in nanoscale
topography (DNA-PAINT) offers an easy-to-implement approach to localization-based
super-resolution microscopy, owing to the use of DNA probes. In DNA-PAINT,
transient binding of short dye-labeled ('imager') oligonucleotides to their
complementary target ('docking') strands creates the necessary 'blinking' to
enable stochastic super-resolution microscopy. Using the programmability and
specificity of DNA molecules as imaging and labeling probes allows researchers to
decouple blinking from dye photophysics, alleviating limitations of current super
resolution techniques, making them compatible with virtually any single-molecule
compatible dye. Recent developments in DNA-PAINT have enabled spectrally
unlimited multiplexing, precise molecule counting and ultra-high, molecular-scale
(sub-5-nm) spatial resolution, reaching ~1-nm localization precision. DNA-PAINT
can be applied to a multitude of in vitro and cellular applications by linking
docking strands to antibodies. Here, we present a protocol for the key aspects of
the DNA-PAINT framework for both novice and expert users. This protocol describes
the creation of DNA origami test samples, in situ sample preparation, multiplexed
data acquisition, data simulation, super-resolution image reconstruction and post
processing such as drift correction, molecule counting (qPAINT) and particle
averaging. Moreover, we provide an integrated software package, named Picasso,
for the computational steps involved. The protocol is designed to be modular, so
that individual components can be chosen and implemented per requirements of a
specific application. The procedure can be completed in 1-2 d.
PMID- 28518178
TI - Physical function and exercise training in older patients with heart failure.
AB - Heart failure (HF) is a common end point for numerous cardiovascular conditions,
including coronary artery disease, valvular disease, and hypertension. HF
predominantly affects older individuals (aged >=70 years), particularly those
living in developed countries. The pathophysiological sequelae of HF progression
have a substantial negative effect on physical function. Diminished physical
function in older patients with HF, which is the result of combined disease
related and age-related effects, has important implications on health. A large
body of research spanning several decades has demonstrated the safety and
efficacy of regular physical activity in improving outcomes among the HF
population, regardless of age, sex, or ethnicity. However, patients with HF,
especially those who are older, are less likely to engage in regular exercise
training compared with the general population. To improve initiation of regular
exercise training and subsequent long-term compliance, there is a need to rethink
the dialogue between clinicians and patients. This Review discusses the need to
improve physical function and exercise habits in patients with HF, focusing on
the older population.
PMID- 28518179
TI - Cleaning, Disinfection, and Sterilization Protocols Employed for Customized
Implant Abutments: An International Survey of 100 Universities Worldwide.
AB - PURPOSE: American and European standards recommend sterilization of customized
abutments before connecting them to implants, as customized abutments are
considered semi-critical medical devices. Since standardized procedures could not
be identified in the literature on implantology, this survey evaluated the
protocols employed at different universities worldwide to clean, disinfect,
and/or sterilize customized abutments before their connection to bone-level
implants. MATERIALS AND METHODS: The survey took place between October 2015 and
January 2016. A single question acquiring information on how customized abutments
were treated prior to connection to the implants was sent by email to researchers
affiliated at 100 universities worldwide. To avoid any bias, the survey was kept
rigorously anonymous. A total of 100 universities from Europe (56), USA and
Canada (25), Latin America (9), South Africa (1), Asia (6), and Australia and New
Zealand (3) were invited to participate in the survey. RESULTS: Altogether, 85
universities responded to the survey question, and 22 (25.9%) declared that no
cleaning protocols were adopted. More than half of the respondents (n = 49,
57.6%) performed only one of the three procedures required by the standards
(cleaning, disinfection, or sterilization). Twelve respondents (14.1%) adopted
two procedures, and only two universities performed all three required procedures
(2.4%). CONCLUSION: This survey indicated substantial heterogeneity in treating
customized abutments before connecting them to implants. This study demonstrated
that the majority of the universities applied either cleaning, disinfection, or
sterilization which may not meet the prevailing standards.
PMID- 28518180
TI - The Effects of Laser with Different Parameters and Crosshatching on Fibroblast
Adhesion and Proliferation to Implant Surfaces.
AB - PURPOSE: To compare the adhesion and proliferation effect of HGF-1 cells on pure
titanium disks when the surfaces are unprocessed (machined surfaces after
slicing) or modified with a laser. MATERIALS AND METHODS: Twenty-eight titanium
disks were divided into four groups. Three surface topographies were created
using an erbium fiber laser: group 1 (unidirectional application [no
crosshatch]), group 2 (crosshatching in two directions), and group 3
(crosshatching in three directions). The samples in group 4 were unprocessed and
served as controls. The surface roughness of samples was investigated with
scanning electron microscopy (SEM) and measured with a mechanical surface
profilometer. HGF-1 cell line was used to analyze the adhesion of fibroblasts on
the sample surfaces. The authors used SEM, XTT, and acridine orange tests to
determine the adhesion of HGF-1 onto specimen surfaces and the cell morphology
after incubation for 72 hours. XTT results and surface roughness values for all
specimens were analyzed using the Kruskal-Wallis test. RESULTS: Ra values of
group 1 to group 4 (control) were 1.13, 0.26, 0.38, and 0.19, respectively.
Crosshatching decreased the surface roughness values compared with unidirectional
application (P = .003). Cell morphology observed in SEM showed that the
elongation direction of cells resulted in all directions related with additional
filopodia extentions within the crosshatch groups. Therefore, the highest cell
viability was also detected in the three-directional crosshatch group (group 3)
(P = .000) in XTT assay. According to the acridine orange test, higher cell
numbers were seen in group 3, similar to the XTT findings (P = .86). CONCLUSION:
Crosshatching significantly increased the cell-covered implant surfaces compared
with the unidirectional group. Decreasing the surface Ra values via crosshatching
helped spread the fibroblast over the implants in any direction, thus increasing
cell proliferation and adhesion.
PMID- 28518176
TI - Seasonal variations in cardiovascular disease.
AB - Cardiovascular disease (CVD) follows a seasonal pattern in many populations.
Broadly defined winter peaks and clusters of all subtypes of CVD after 'cold
snaps' are consistently described, with corollary peaks linked to heat waves.
Individuals living in milder climates might be more vulnerable to seasonality.
Although seasonal variation in CVD is largely driven by predictable changes in
weather conditions, a complex interaction between ambient environmental
conditions and the individual is evident. Behavioural and physiological responses
to seasonal change modulate susceptibility to cardiovascular seasonality. The
heterogeneity in environmental conditions and population dynamics across the
globe means that a definitive study of this complex phenomenon is unlikely.
However, given the size of the problem and a range of possible targets to reduce
seasonal provocation of CVD in vulnerable individuals, scope exists for both
greater recognition of the problem and application of multifaceted interventions
to attenuate its effects. In this Review, we identify the physiological and
environmental factors that contribute to seasonality in nearly all forms of CVD,
highlight findings from large-scale population studies of this phenomenon across
the globe, and describe the potential strategies that might attenuate peaks in
cardiovascular events during cold and hot periods of the year.
PMID- 28518183
TI - Preclinical Evaluation of a Crown-Splinted Custom Root-Shaped Implant.
AB - OBJECTIVE: To test whether a Maryland bridge-type splint provides adequate
stability for a custom root-shaped implant to osseointegrate in a manner
substantially equivalent to that of a threaded implant. METHODS: Six beagle dogs
were subjected to intraoral impressions and cone beam scans that were used to
fabricate custom root-shaped implants (RTIs) and crowns. Premolars in the
mandible (P4) and in the maxilla (P3) were extracted, and 24 RTIs were
immediately placed in extraction sockets. Splint extensions of the crowns were
bonded to mesial and distal teeth. Twelve mandibular molars (M2) were extracted,
and threaded implants (DXI), serving as controls, were placed immediately.
Animals were placed on a soft diet after surgery. Weekly intraoral photographs
and radiographs were taken, and animals were sacrificed at 4 months. Fluorescent
labels were injected 35, 21, and 7 days before sacrifice. Clinical implant
stability and vertical pullout forces were tested, and loss of vertical bone
height was measured on radiographs. Histomorphometric measurements of percent
bone-to-implant contact (BIC) and mineral apposition rates were made from
undecalcified sections. RESULTS: Three RTI splints broke or debonded, and the
implants were removed. No loss of DXI implants was noted. All remaining implants
were clinically stable. Mean pullout forces were 366.7 +/- 182.8 N for RTI (no
pullout data for the threaded DXI). Mean vertical bone loss was 0.4 +/- 0.6 mm
mesially and 0.2 +/- 0.7 mm distally for RTI and 0.8 +/- 1.1 mm mesially and 0.8
+/- 1.0 mm distally for DXI, with no significant differences between groups. BIC
values were 70.8% +/- 12.7% for mandibular RTI, 68.3% +/- 11.6% for maxillary
RTI, and 78.8% +/- 5.5% for DXI. Mineral apposition rates within local osteons
were 1.9 +/- 0.5 MUm for RTI and 1.7 +/- 0.3 MUm for DXI; at the implant surface,
they were 2.5 +/- 1.2 MUm for RTI and 3.3 +/- 1.8 MUm for DXI, with no
significant differences between groups. CONCLUSION: All RTIs with intact splints
exhibited clinically successful integration, similar to that of control threaded
implants. The RTI may be a viable option for single-tooth replacement.
PMID- 28518181
TI - A Semi-automatic Algorithm for Preliminary Assessment of Labial Gingiva and
Alveolar Bone Thickness of Maxillary Anterior Teeth.
AB - PURPOSE: Soft and hard tissue volumes are critical for implant placement and long
term stability. Although the literature has adequately addressed tissue biotypes
of Western populations, pertinent information about Asian populations is limited.
This study aimed to evaluate the soft and hard tissue profiles of the maxillary
anterior teeth of the Taiwanese population using a semi-automatic algorithm.
MATERIALS AND METHODS: Cone beam computed tomography images of 11 adults with
well-aligned maxillary anterior teeth were overlaid with those of cast models,
based on the tooth crowns manually outlined by two independent observers. Each
tooth was digitally trisected mesiodistally and apicocoronally. The thicknesses
of the labial gingiva and alveolar bone were measured using a customized software
program. RESULTS: No obvious difference between the observers was noted regarding
the dimension of tooth crowns. The average thicknesses of the labial gingiva, the
labial alveolar bone, and the palatal alveolar bone were 1.76 +/- 0.11 mm, 1.02
+/- 0.12 mm, and 1.80 +/- 0.31 mm, respectively, with no significant differences
between teeth. All parameters were thicker in the apical region than in the
cervical region, and the alveolar bone was thinner in the midlabial region of
incisors than in the interproximal regions. The thinnest areas were the
midcervical compartment of the right central incisor (0.53 +/- 0.33 mm) for the
labial gingiva, the midcervical compartment of the right lateral incisor (0.23 +/
0.10 mm) for the labial alveolar bone, and the mesiocervical compartment of the
left central incisor (0.33 +/- 0.09 mm) for the palatal alveolar bone.
CONCLUSION: This study presents an objective and comprehensive methodology for
evaluating the soft and hard tissue profiles of maxillary anterior teeth and may
be of value for presurgical planning for immediate implant placement. The results
suggest that profiles of the Taiwanese subjects are similar to profiles of
Western populations.
PMID- 28518182
TI - Triple-Layered Closure of an Oroantral Fistula: A Case Report.
AB - Oroantral fistulae (OAF) are surgical sequelae that require complete resection
and often leave large defects for the surgeon to repair. Closing these lesions is
often technique sensitive and requires a detailed protocol, which, if not adhered
to, can lead to recurrence. This case report presents a combined approach to
closing an OAF by first excising the fistula and then resecting to retrieve the
buccal fat pad to form a pedicle graft over the wound site. Next, a platelet-rich
fibrin membrane is sandwiched over the buccal fat pad and completely covered by a
buccal advancement flap. This triple-layered technique is a novel method to close
a chronic OAF.
PMID- 28518184
TI - A Method for Minimizing Rotational Errors of Implant Prostheses.
AB - PURPOSE: Rotational errors of implants can occur during two stages: when
connecting impression copings with implants, and when connecting impression
copings with analogs. The aim of this study was to determine ways to minimize
these rotational errors. MATERIALS AND METHODS: Three types of implants were
prepared: a tissue-level implant with an internal octagon 8-degree Morse taper
connection, a bone-level implant with an internal hex 11-degree Morse taper
connection, and a bone-level implant with an external hex connection. Each
complex (n = 10 per group) was composed of an implant, an impression coping, and
an analog. Implants were embedded in resin blocks and connected with
corresponding impression copings. Analogs that reproduced the position of the
implants were created by means of a custom-made transfer jig, and rotational
errors were measured between implants and analogs. Impression copings and analogs
were connected by means of four methods: The impression coping was connected to
the implant in a clockwise (CW) or a counterclockwise (CCW) direction before
tightening, and the analogs were then connected with impression copings and
tightened using a hemostat (Hs) or by hand (Hd). RESULTS: The CW-Hs and CCW-Hd
groups exhibited low rotational error (mean +/- standard deviation 0.11 +/- 0.21
and 0.19 +/- 0.34 degrees, respectively), whereas the CW-Hd and CCW-Hs groups
exhibited high rotational error (-1.80 +/- 0.67 and 2.07 +/- 0.75, respectively)
in different directions. A strong association was observed between the tightening
method and rotational error, and a weak association was observed between the
connection type and rotational error. CONCLUSION: The CW-Hs method was found to
be the most suitable for minimizing rotational error between implants and
analogs.
PMID- 28518185
TI - Osteogenic Potential of Adipose-Derived Macrospheroids Cocultured with CD11b+
Monocytes.
AB - PURPOSE: Among potential cell-based therapies, adipose-derived stem cells (ASCs)
have been proposed as a promising source of stem cells for tissue regeneration.
Although many recent clinical trials have investigated the use of adipose tissue
or ASCs in transplantation, analysis of the microstructures of outgrowing
macrosized spheroids (macrospheroids) or three-dimensional coculture of ASC
spheroids and monocyte/macrophage lineages has not been performed. The aim of
this study was to analyze the microstructures of murine-derived ASC
macrospheroids and the growth and osteogenic potential of these macrospheroids in
a three-dimensional environment and after calcification induction by coculture
with monocytes. MATERIALS AND METHODS: The histologic structures of murine
derived ASC macrospheroids and the expression of marker genes for multipotency
within these macrospheroids were analyzed by hematoxylin and eosin staining and
in situ hybridization. ASC macrospheroid microstructures were observed by
transmission electron microscopy, and cell proliferation in the spheroids was
analyzed. Additionally, the growth and osteogenic potential of these
macrospheroids were assessed in two-dimensional and three-dimensional
environments and after calcification induction by coculture with monocytes.
RESULTS: The expression of Oct3/4, Nanog, and Sox2 was detected even in the deep
zone of spheroids, although higher expression was observed at the surface. Cell
proliferation was detected within the spheroid centers. Observation of spheroid
microstructure revealed extracellular matrix production within the spheroid
architecture. Transplantation of a spheroid on the hydroxyapatite disc resulted
in three-dimensional cell growth, filling the disc. Coculture of the spheroids
with monocytes led to the formation of many osteoclast-like, multinucleated
cells, and calcification was observed after 3 weeks of coculture. CONCLUSION: ASC
spheroids exhibited high capacity for dynamic three-dimensional growth and
osteogenic differentiation. Furthermore, ASC spheroids promoted monocyte
differentiation into osteoclast-like cells, which may enhance the osteogenic
potential of ASC spheroids.
PMID- 28518186
TI - Molecular Activity and Osseointegration After Single-Dose Irradiation: An In Vivo
Study.
AB - PURPOSE: Irradiation results in deleterious effects on bone healing and
integration of titanium implants. The impact of irradiation on osseointegration
has been demonstrated in histologic studies, but the underlying molecular
mechanisms have not been explored. This study aimed to investigate the effects of
single-dose irradiation on the expression of biologic mediators crucial for
inflammation, bone formation, and bone remodeling and to relate these molecular
activities to implant stability after a 5-week healing period. MATERIALS AND
METHODS: A rat tibia model was used. An external single-dose irradiation of 20 Gy
was administered to one leg while the second leg was used as a control. After 8
weeks, the irradiated and non-irradiated tibiae received titanium implants. Five
weeks following implantation, implant stability was evaluated by removal torque
measurement. Then, the implant and the bone surrounding the implant were
retrieved for gene expression analysis of the implant-adherent cells and peri
implant bone, respectively. RESULTS: Irradiation resulted in 55% reduction in
removal torque. The implant-adherent cells in irradiated sites revealed
downregulation of genes related to bone formation (ALP and OC) and upregulation
of proinflammatory (TNF-alpha) and pro-fibrogenic (PDGF-b) genes. Conversely, the
peri-implant bone in irradiated sites revealed upregulation of bone formation and
bone remodeling genes. Removal torque showed a negative correlation with pro
inflammatory activity and a positive correlation with osteoblastic activity in
the implant-adherent cells. CONCLUSION: The impact of high (20 Gy) single-dose
irradiation on osseointegration involves a reduction in bone formation activity
and upregulation of pro-inflammatory and pro-fibrogenic activities in the implant
adherent cells. It is also suggested that this single-dose irradiation elicits a
different molecular pattern at a distance from the implant surface, characterized
by increased bone formation and remodeling activities in the peri-implant bone.
PMID- 28518187
TI - In Vitro Shock Absorption Tests on Implant-Supported Crowns: Influence of Crown
Materials and Luting Agents.
AB - PURPOSE: To investigate the force absorption capacity of implant-supported crowns
made of different restorative materials and connected to abutments with different
luting agents. MATERIALS AND METHODS: Molar crowns were milled of different
computer-aided design/computer-aided manufacture materials (n = 8 crowns per
material): polymethyl methacrylate, polyether ether ketone, composite, lithium
disilicate, titanium, and zirconia. Crowns were mounted on titanium implant
replicas using different luting agents: uncemented, temporarily cemented (zinc
oxide-eugenol cement), conventionally cemented (zinc oxide phosphate cement), and
adhesively bonded. As a reference, one implant replica was tested without a
crown. Force absorptions of the different combinations of crown materials and
luting agents were determined by applying an increasing force (0 to 250 N) on the
occlusal crown surface and measuring the resulting force below the implant. Mean
curves of applied and resulting forces up to 200 N were determined (six
measurements per group), and slopes were calculated. Statistical analysis was
performed (one-way analysis of variance, Bonferroni post hoc test, alpha = .05).
RESULTS: Significant (P < .001) differences in the applied and resulting forces
were found between the crown materials that were uncemented, temporarily
cemented, cemented, and adhesively bonded. Materials with higher moduli of
elasticity (ceramics, titanium) showed steeper slopes of the force curves and
lower shock-absorbing capacity than resin-based materials, but were influenced
more by the luting agents. The damping effects of resin-based materials were
higher in combination with all cementation and luting modes. CONCLUSION: Shock
absorption tests exhibited a strong material-dependent damping behavior of
implant-supported crowns. The shock-absorbing capacity of crown materials with
high moduli of elasticity may benefit from conventional cementation.
PMID- 28518189
TI - Structure and dynamics of water confined in a graphene nanochannel under
gigapascal high pressure: dependence of friction on pressure and confinement.
AB - Recently, water flow confined in nanochannels has become an interesting topic due
to its unique properties and potential applications in nanofluidic devices. The
trapped water is predicted to experience high pressure in the gigapascal regime.
Theoretical and experimental studies have reported various novel structures of
the confined water under high pressure. However, the role of this high pressure
on the dynamic properties of water has not been elucidated to date. In the
present study, the structure evolution and interfacial friction behavior of water
constrained in a graphene nanochannel were investigated via molecular dynamics
simulations. Transitions of the confined water to different ice phases at room
temperature were observed in the presence of lateral pressure at the gigapascal
level. The friction coefficient at the water/graphene interface was found to be
dependent on the lateral pressure and nanochannel height. Further theoretical
analyses indicate that the pressure dependence of friction is related to the
pressure-induced change in the structure of water and the confinement dependence
results from the variation in the water/graphene interaction energy barrier.
These findings provide a basic understanding of the dynamics of the nanoconfined
water, which is crucial in both fundamental and applied science.
PMID- 28518188
TI - pH-Dependent absorption spectrum of a protein: a minimal electrostatic model of
Anabaena sensory rhodopsin.
AB - A minimal electrostatic model is introduced which aims at reproducing and
analyzing the visible-light absorption energy shift of a protein with pH. It
relies on the existence of a protein structure, the prediction of titratable
amino-acid pKa values and a very limited set of parameters. Applied to the case
of the photochromic Anabaena sensory rhodopsin protein, the model succeeds in
reproducing qualitatively the reported experimental data, confirming the
importance of aspartic acid 217 in the observed blue shift in the lambdamax of
ASR at neutral pH. It also suggests for the first time the role of two other
amino acids, glutamic acid 36 at basic pH and aspartic acid 120 at acidic pH.
PMID- 28518190
TI - Sequential incorporation of metallic cations (Cd2+ and Hg2+) and N-octylamine
into titanium phosphate nanoparticles and their subsequent release in acid media.
AB - Titanium phosphate nanoparticles, TPNP, consisting of a NaTi2(PO4)3 core and a
shell of hydrogen phosphate and dihydrogen phosphate of titanium, undergo fast
hydrolysis in water releasing phosphoric acid. This reaction is inhibited in the
presence of metallic ions like Cd2+ or Hg2+, which are able to replace the
protons of the shell acid phosphates. The amount of the adsorbed metallic cations
could be regulated using counterions of different basicity. The resulting
nanoparticles also incorporate NH2(CH2)7CH3 (N-octylamine) at room temperature
forming N-octylammonium/phosphate ion pairs, but it was found that at higher
cation concentration inside the nanoparticle, a lower amount of amine was
adsorbed. The metallic cations and N-octylamine are released in acid media, but
the starting material is not fully recovered.
PMID- 28518191
TI - LaTiO2N-LaCrO3: continuous solid solutions towards enhanced photocatalytic H2
evolution under visible-light irradiation.
AB - (LaTiO2N)1-x(LaCrO3)x continuous solid solutions with an orthorhombic-phase ABX3
perovskite structure and with varied LaCrO3 contents (0 <= x <= 1) were
synthesized by a polymerized complex method followed by a post-treatment process
of nitridation for the first time. Visible-light-driven photocatalytic H2
evolution activities of the solid solutions gradually increased with the increase
of x from 0.0 to 0.3, and then sharply decreased with the further increase of x
from 0.3 to 1.0. With the increase of x, on the one hand, the narrowed bandgaps
of solid solutions would enhance the generation of charge carriers and the
increased lattice distortion of solid solutions could promote the separation and
migration of charge carriers, thus mainly contributing to the improvement of
photocatalytic activities; on the other hand, the lowered CBMs of solid solutions
would reduce the driving force for reducing H2O to H2 and the decreased surface
areas of solid solutions would weaken the adsorption of reactants and reduce the
reactive sites, thereby resulting in the deterioration of photocatalytic
activities.
PMID- 28518193
TI - 4N electron aromatic cycles in polycyclic hydrocarbons.
AB - Polycyclic fully conjugated hydrocarbons in which aromatics are fused to
aromatics - or aromatics to antiaromatics - are important as potential organic
semiconductors. Herein we explore the only remaining fusion pattern of
antiaromatics to antiaromatics. It is shown computationally that the central
antiaromatic unit (cyclobutadiene or pentalene) in such a three-unit polycyclic
hydrocarbon, generated by fusion of three antiaromatic molecules, turns aromatic
according to magnetic shielding (NICS) criteria. The resulting neutral 4N
electron molecules possess a 4N pi electron perimeter with pronounced CC bond
length equalization (as indicated by the HOMA geometric index) and significant
aromatic stabilization energies (computed using the isomerization-stabilization
method) and could be promising synthetic targets with small HOMO-LUMO gaps.
PMID- 28518192
TI - Time-resolved signatures across the intramolecular response in substituted
cyanine dyes.
AB - The optically populated excited state wave packet propagates along
multidimensional intramolecular coordinates soon after photoexcitation. This
action occurs alongside an intermolecular response from the surrounding solvent.
Disentangling the multidimensional convoluted signal enables the possibility to
separate and understand the initial intramolecular relaxation pathways over the
excited state potential energy surface. Here we track the initial excited state
dynamics by measuring the fluorescence yield from the first excited state as a
function of time delay between two color femtosecond pulses for several cyanine
dyes having different substituents. We find that when the high frequency pulse
precedes the low frequency one and for timescales up to 200 fs, the excited state
population can be depleted through stimulated emission with efficiency that is
dependent on the molecular electronic structure. A similar observation at even
shorter times was made by scanning the chirp (frequencies ordering) of a
femtosecond pulse. The changes in depletion reflect the rate at which the nuclear
coordinates of the excited state leave the Franck-Condon (FC) region and progress
towards achieving equilibrium. Through functional group substitution, we explore
these dynamic changes as a function of dipolar change following photoexcitation.
Density functional theory calculations were performed to provide greater insight
into the experimental spectroscopic observations. Complete active space (CAS)
self-consistent field and CAS second order perturbation theory calculated
potential energy surfaces tracking twisting and pyramidalization confirm that the
steeper potential at the FC region leads to the observation of faster wave packet
dynamics.
PMID- 28518194
TI - Detection of antibiotic resistant Escherichia Coli bacteria using infrared
microscopy and advanced multivariate analysis.
AB - Bacterial resistance to antibiotics is becoming a global health-care problem.
Bacteria are involved in many diseases, and antibiotics have been the most
effective treatment for them. It is essential to treat an infection with an
antibiotic to which the infecting bacteria is sensitive; otherwise, the treatment
is not effective and may lead to life-threatening progression of disease.
Classical microbiology methods that are used for determination of bacterial
susceptibility to antibiotics are time consuming, accounting for problematic
delays in the administration of appropriate drugs. Infrared-absorption microscopy
is a sensitive and rapid method, enabling the acquisition of biochemical
information from cells at the molecular level. The combination of Fourier
transform infrared (FTIR) microscopy with new statistical classification methods
for spectral analysis has become a powerful technique, with the ability to detect
structural molecular changes associated with resistivity of bacteria to
antibiotics. It was possible to differentiate between isolates of Escherichia
(E.) coli that were sensitive or resistant to different antibiotics with good
accuracy. The objective computational classifier, based on infrared absorption
spectra, is highly sensitive to the subtle infrared spectral changes that
correlate with molecular changes associated with resistivity. These changes
enable differentiating between the resistant and sensitive E. coli isolates
within a few minutes, following the initial culture. This study provides proof-of
concept evidence for the translational potential of this spectroscopic technique
in the clinical management of bacterial infections, by characterizing and
classifying antibiotic resistance in a much shorter time than possible with
current standard laboratory methods.
PMID- 28518195
TI - Integrated pretreatment and desalination by electrocoagulation (EC)-ion
concentration polarization (ICP) hybrid.
AB - Conventional water treatment process is composed of multiple stages, including
desalination (salt removal) and pre/post-treatment of desalination to remove
particles, chemicals, and other potential foulants for desalination. In this
work, we developed a microfluidic proof-of-concept for a single device water
treatment system, which removes both salt ions and non-salt contaminants. Our
system combines electrocoagulation (EC), a versatile contaminant removal process,
and ion concentration polarization (ICP) desalination, which is an
electromembrane desalination process. We demonstrated a continuous EC-ICP
operation that removed >95% of suspended solids and reduced the salinity from
brackish range (20 mM NaCl) to a potable level (<8.6 mM NaCl). We also
demonstrated that our system is flexible in terms of the type and concentration
of contaminants it can handle. Combining two different electrochemical processes
into a single system, we can reduce unnecessary voltage drop by having a shared
anode, and achieve both seamless integration and energy efficient operation. Our
system will find applications as a small-scale water treatment system, if
properly scaled up in the future.
PMID- 28518198
TI - Photophysical properties and excited state dynamics of 4,7-dithien-2-yl-2,1,3
benzothiadiazole.
AB - The relationships between the photophysics and structural properties of 4,7
dithien-2-yl-2,1,3-benzothiadiazole as a function of solvent polarity are
investigated both experimentally and by computational methods. Stationary
fluorescence measurements are consistent with a model envisaging the presence of
three types of conformers in equilibrium in the ground state. They are
characterized by different relative orientations of the thiophene rings. Due to a
low rotational barrier, the sample in solution is characterized by a distribution
of relative internal orientations. By applying the Kawski method, we evaluate the
average dipole moment of ground and excited states of the three types of
conformers. The ground state dipole moments are small and similar for the three
types of conformers. On the contrary, dipole moments differ substantially in the
excited state. X-ray diffraction of a single crystal confirms the presence of an
orientational disorder of thiophene rings. Transient absorption UV-visible
spectroscopy experiments allows the identification of the main mechanisms
responsible for the large Stokes shift observed in this push-pull molecule. Time
dependent spectra provide a picture of the relaxation processes occurring after
excitation: the primary step is an internal charge transfer assisted by thiophene
ring planarization which occurs on a time scale ranging from 0.88 to 1.3
picoseconds depending on solvent polarity. Moreover, time-resolved fluorescence
measurements are consistent with a mechanism involving planarization accompanied
by a stabilization of the charge transfer state as observed in polar solvents. In
the latter, longer fluorescence lifetimes are observed along with a quantum yield
decrease due to the activation of specific non-radiative relaxation channels. The
photophysical behavior of 4,7-dithien-2-yl-2,1,3-benzothiadiazole in a solid
matrix of polymethyl methacrylate is similar to that observed in solution, but
the overall non-radiative process rate is slow with respect to that in the liquid
phase. As a consequence, the radiative processes are enhanced giving rise to a
fluorescence quantum yield of 90%. Such behavior is consistent with the proposed
relaxation model.
PMID- 28518199
TI - Cluster-based MOFs with accelerated chemical conversion of CO2 through C-C bond
formation.
AB - Investigations on metal-organic frameworks (MOFs) as direct catalysts have been
well documented, but direct catalysis of the chemical conversion of terminal
alkynes and CO2 as chemical feedstock by MOFs into valuable chemical products has
never been reported. We report here two cluster-based MOFs I and II assembled
from a multinuclear Gd-cluster and Cu-cluster, displaying high thermal and
solvent stabilities. I and II as heterogeneous catalysts possess active catalytic
centers [Cu12I12] and [Cu3I2], respectively, exhibiting excellent catalytic
performance in the carboxylation reactions of CO2 with 14 kinds of terminal
alkynes under 1 atm and mild conditions. For the first time catalysis of the
carboxylation reaction of terminal alkynes with CO2 by MOF materials without any
cocatalyst/additive is reported. This work not only reduces greenhouse gas
emission but also provides highly valuable materials, opening a wide space in
seeking recoverable catalysts to accelerate the chemical conversion of CO2.
PMID- 28518200
TI - Multichromophoric hybrid species made of perylene bisimide derivatives and Ru(ii)
and Os(ii) polypyridine subunits.
AB - Herein, the synthesis and the photophysical and redox properties of a new
perylene bisimide (PBI) species (L), bearing two 1,10-phenanthroline (phen)
ligands at the two imide positions of the PBI, and its dinuclear Ru(ii) and
Os(ii) complexes, [(bpy)2Ru(MU-L)Ru(bpy)2](PF6)4 (Ru2; bpy = 2,2'-bipyridine) and
[(Me2-bpy)2Os(MU-L)Os(Me2-bpy)2](PF6)4 (Os2; Me2-bpy = (4,4'-dimethyl)-2,2'
bipyridine), are reported. The absorption spectra of the compounds are dominated
by the structured bands of the PBI subunit due to the lowest-energy spin-allowed
pi-pi* transition. The spin-allowed MLCT transitions in Ru2 and Os2 are inferred
by the absorption at 350-470 nm, where the PBI absorption is negligible. The
absorption band extends towards the red region for Os2 due to the spin-forbidden
MLCT transitions, intensified by the heavy osmium center. The reduction processes
of the compounds are dominated by two successive mono-electronic PBI-based
processes, which in the metal complexes are slightly shifted compared to the free
ligand. On oxidation, both metal complexes undergo an apparent bi-electronic
process (at 1.31 V vs. SCE for Ru2 and 0.77 V for Os2), attributed to the
simultaneous one-electron oxidation of the two weakly-interacting metal centers.
In Ru2 and Os2, the intense fluorescence of L subunit (lambdamax, 535 nm; tau,
4.3 ns; Phi, 0.91) is fully quenched, mainly by photoinduced electron transfer
from the metal centers, on the ps timescale (time constant, 11 ps in Ru2 and 3 ps
in Os2). Such photoinduced electron transfer leads to the formation of a charge
separated state, which directly decays to the ground state in about 70 ps in Os2,
but produces the triplet pi-pi* state of the PBI subunit in 35 ps in Ru2. The
results provide information on the excited-state processes of the hybrid species
combining two dominant classes of chromophore/luminophore species, the PBI and
the metal polypyridine complexes, and can be used for future design on new hybrid
species with made-to-order properties.
PMID- 28518201
TI - A general diastereoselective synthesis of highly functionalized ferrocenyl
ambiphiles enabled on a large scale by electrochemical purification.
AB - A general synthesis of highly functionalized ferrocenes, which include (P,B)- and
(N,B)-ambiphiles, has been developed at a multigram scale. Diastereoselective
stepwise modification of di-tert-butylated ferrocenes included the unprecedented
separation of electroactive species. Bulky alkyl groups on ferrocenes ensure
planar chirality of ambiphiles and enforce closer proximity of antagonist Lewis
functions.
PMID- 28518202
TI - Improved reactivity of a cyclic 13/15 compound by increased steric demand.
AB - Herein we present the synthesis and characterization of the new four-membered
Ga/P cycle [tBu2GaP(H)SitBu2Ph]2, which shows a cis/trans isomerization at
ambient temperatures via a ring opening mechanism. The sterically demanding
substituents on the phosphorus (-SitBu2Ph) and gallium (tBu) atoms lead to an
unexpected reactivity towards bulky NHC ligands (IMes and IDipp). The resulting
Lewis base stabilized monomeric 13/15 compounds feature an unusual binding mode
of the carbene ligand. The ring opened state also enables a masked flp
reactivity, which is shown by a reaction with the polar multiple bond in Ph-NCO.
PMID- 28518204
TI - Integrated metabolomics and metallomics analyses in acute coronary syndrome
patients.
AB - Acute coronary syndrome (ACS) is the leading cause of morbidity and mortality.
Accurate risk prediction in ACS patients is critically important for helping
clinicians make therapeutic decisions, such as recommending a more aggressive
intervention and intensive follow-up. However, risk stratification in ACS
patients remains challenging, and the identification of novel predictors is
necessary for improving the prognostic prediction in ACS patients. We employed
metallomics and untargeted metabolomics approaches to discover new biomarkers
from the plasma samples of 20 ACS patients and 20 non-ACS patients. We identified
metabolic changes related to lysophosphatidylcholines, caffeine, glycolysis,
tryptophan and sphingomyelin metabolism (p value <0.05) that were perturbed in
the ACS patients. Moreover, circulating metal elements, including Mg, Ca, K, Zn,
Ni, Ga and In (p value <0.05), were altered in the ACS patients versus the
controls. These changes suggest possible changes in cell membrane permeability
and rigidity in ACS patients.
PMID- 28518205
TI - Self-assembly of amphiphilic tripeptides with sequence-dependent nanostructure.
AB - Supramolecular chemistry enables the creation of a diversity of nanostructures
and materials. Many of these have been explored for applications as biomaterials
and therapeutics. Among them, self-assembling peptides have been broadly applied.
The structural diversity afforded from the library of amino acid building blocks
has enabled control of emergent properties across length-scales. Here, we report
on a family of amphiphilic tripeptides with sequence-controlled nanostructure. By
altering one amino acid in these peptides, we can produce a diversity of
nanostructures with different aspect-ratio and geometry. Peptides that produce
high aspect-ratio structures can physically entangle to form hydrogels, which
support cell viability in culture. Importantly, in comparison to many other short
self-assembling peptide biomaterials, those reported here form filamentous
nanostructures in the absence of typical secondary structures (i.e., beta-sheet).
Thus, we have illustrated a facile way to obtain versatile biomaterials with
different nanostructural morphology from short and defined peptide sequences.
PMID- 28518206
TI - Organocatalytic hydroborylation promoted by N-heterocyclic olefins.
AB - New complexes containing N-heterocyclic vinylene-stabilized [B2H5]+ fragments
were prepared, and surprisingly it was found that the precursor N-heterocyclic
olefins (NHOs) could promote the mild (room temperature) catalytic
hydroborylation of ketones and aldehydes. This finding represents an important
addition to the burgeoning field of non-metal mediated catalysis.
PMID- 28518207
TI - Influence of particle size and dielectric environment on the dispersion behaviour
and surface plasmon in nickel nanoparticles.
AB - Nickel nanoparticles (NPs) are promising candidates for various applications,
including biomedical ones, as they have good magnetic properties as well as high
thermal conductivity. We used well-characterized Ni NPs of average Scherrer sizes
from 1.31 nm to 22.23 nm and investigated the effects of the primary particle
size, size distribution and dielectric environments, and of separately adding non
ionic polyvinylpyrrolidone (PVP), cationic cetyltrimethylammonium bromide (CTAB)
and anionic ethylenediaminetetraacetic acid (EDTA) in ethanol, on their stability
and agglomeration behaviour using atomic force microscopy (AFM), particle size
analysis and zeta potential study through dynamic light scattering (DLS) combined
with UV-visible spectroscopy data. The dominant influence of surfactants,
additives, particles size and shape on the surface plasmon resonance (SPR) was
found. SPR is considerably sensitive to the dielectric environment in addition to
size and shape. Moreover, increasing the concentration of PVP led to an enhanced
SPR intensity and a shift in its position towards higher wavelength. 1.31 nm NPs
with EDTA as an additive yielded the best dispersibility and also showed
superparamagnetic behaviour at 300 K, indicating their favourable application
potentials.
PMID- 28518210
TI - Regular graveyard in the stronghold versus settlement burials in the bailey.
Comparison of Early Medieval populations from Pohansko (Czech Republic).
AB - ABSTRACT: The aim of the study is to identify possible differences in the
prevalence of biological stress markers (cribra orbitalia, linear enammel
hypoplasia), dental caries, activity markers (Schmorl's nodes) and markers of
violence (traumatic lesions) in populations from a typical graveyard around the
first church (9th-10th century AD) in the stronghold and from settlement burials
in the southern bailey (second half of the 9th - beginning of the 10th century
AD) of Slavs from Pohansko (Czech Republic). Cribra orbitalia and enamel
hypoplasia did not markedly differ in either population. On the other hand, co
occurrence of both markers was statistically different and distinction in higher
age categories could indicate diverse living conditions. Lower cariousness in the
population from the southern bailey was identified. The nature of postcranial
traumatic lesions in both populations indicates rather their accidental origin.
However, a higher incidence of cranial injuries points to more violent activities
in the population from Pohansko compared to Mikulcice. A high number of healed
face injuries in males from the southern bailey could indicate higher intragroup
violence in this population.
PMID- 28518211
TI - Inhibition of EGFR nuclear shuttling decreases irradiation resistance in HeLa
cells.
AB - INTRODUCTION: Cervical cancer is a leading cause of mortality in women worldwide.
The resistance to irradiation at the advanced stage is the main reason for the
poor prognosis and high mortality. This work aims to elucidate the molecular
mechanism underlying the radio-resistance. MATERIAL AND METHODS: In this study,
we determined the pEGFR-T654 and pDNA-PK-T2609 expression level changes in
irradiated HeLa cells treated with T654 peptide, a nuclear localization signal
(NLS) inhibitor, to inhibit EGFR nuclear transport. Cell viability, cell cycle
and migratory capacity were analyzed. Xenograft animal model was used to evaluate
the effect of EGFR nuclear transport inhibition on the tumor growth in vivo.
RESULTS: The enhanced translocation of nuclear EGFR in the irradiated HeLa cells
correlated with the increasing level of pEGFR-T654 and pDNA-PK-T2609. Inhibition
of EGFR nuclear translocation by NLS peptide inhibitor attenuated DNA damage
repair in the irradiated HeLa cells, decreased cell viability and promoted cell
death through arrest at G0 phase. NLS peptide inhibitor impaired the migratory
capacity of irradiated HeLa cells, and negatively affected tumorigenesis in
xenograft mice. CONCLUSIONS: This work puts forward a potential molecular
mechanism of the irradiation resistance in cervical cancer cells, providing a
promising direction towards an efficient therapy of cervical cancer.
PMID- 28518212
TI - Evaluation of cytotoxicity and pH changes generated by various dental pulp
capping materials - an in vitro study.
AB - INTRODUCTION: Various materials are used in direct dental pulp capping method.
Their biocompatibility and alkalizing abilities are of primary importance
affecting therapeutic effects. The aim of this study was to evaluate and compare
the cytotoxicity of various pulp-capping materials on human gingival fibroblasts
and investigate the pH changes induced by these materials. MATERIAL AND METHODS:
Human gingival fibroblasts were cultured with nine direct pulp materials using
culture plate inserts. The cytotoxic effects were recorded by using an MTT-based
colorimetric assay after 3 and 24 h. In the second part of the experiment, the
materials were inserted in dialysis tubes and transferred into plastic vials
containing deionized water. The changes of the medium pH were measured after 3
and 24 h. RESULTS: We showed differences in cell viability of gingival
fibroblasts after varied time of exposition for the tested materials. Cell
viability after 24 h increased for Dycal, Biopulp, and Calcipro, and decreased
for Calcipulpe, Angelus, Angelus White, and ProRoot Regular. Cell viability for
ProRoot and Life did not change. Non-setting calcium hydroxide preparations
followed by the MTA group and setting calcium hydroxide materials produced the
highest pH. All the tested materials significantly increased pH (p < 0.0001) at
24 h. CONCLUSIONS: Currently used pulp capping materials varied in their
cytotoxicity relative to human gingival fibroblasts and their alkalizing
capacities. Since most likely pH does not affect the viability of cultured cells,
further investigations are required to determine physicochemical properties of
these materials and the biological activity of the dental pulp.
PMID- 28518213
TI - Relationship between toll-like receptor 2 R753Q and T16934A polymorphisms and
Staphylococcus aureus nasal carriage.
AB - BACKGROUND: The association among specific single-nucleotide polymorphisms (SNPs)
in TLR2 R753Q (rs5743708) and T16934A (rs4696480) and the nasal carriage of
Staphylococcus aureus was studied in adults before CABG. METHODS: The TLR2
polymorphisms were genotyped in 299 consecutive patients prepared for a CABG
operation. Genotyping was performed using restriction fragment length
polymorphism (RFLP) analysis of PCR-amplified fragments. Two nasal swab cultures
were taken within 2 weeks before the operation. Subjects were classified as
Staphylococcus aureus carriers if at least one culture was positive while those
patients with both cultures found to be negative were classified as non-carriers.
RESULTS: The prevalence of nasal S. aureus carriage in the final cohort was 22.1%
(66/299), while no MRSA was detected in our study group. No significant
differences in the TLR2 polymorphisms were observed between the study and the
control groups. No associations were found between TLR2 haplotypes and the
covariates of age, sex, NYHA, weight, height, BMI, CAD, smoking status and ESlog
score. No differences were found between carriers and noncarriers regarding the
allelic distribution of the TLR2 T-16934A SNP. Almost 93% of the patients who
were screened for the presence of the TLR2 Arg753Gln (rs5743708) were GG wild
type homozygous. Twenty one subjects from the study group (7.1%) were GA
heterozygous, while no patient in either group was homozygous for the TLR2
Arg753Gln (rs5743708) mutation. TLR2 Arg753Gln genotyping showed that GA
heterozygous patients were detected more frequently in the group of
Staphylococcus aureus nasal carriers than in non-carrier adults. CONCLUSION: Our
results suggest that the carrier status for the GA variant of the TLR2 Arg753Gln
(rs5743708) polymorphism may be a risk factor for Staphylococcus aureus carriage.
PMID- 28518215
TI - The Toll-like receptor 9 signalling pathway regulates MR1-mediated bacterial
antigen presentation in B cells.
AB - Mucosal-associated invariant T (MAIT) cells are conserved T cells that express a
semi-invariant T-cell receptor (Valpha7.2 in humans and Valpha19 in mice). The
development of MAIT cells requires the antigen-presenting MHC-related protein 1
(MR1), as well as commensal bacteria. The mechanisms that regulate the functional
expression of MR1 molecules and their loading with bacterial antigen in antigen
presenting cells are largely unknown. We have found that treating B cells with
the Toll-like receptor 9 (TLR9) agonist CpG increases MR1 surface expression.
Interestingly, activation of TLR9 by CpG-A (but not CpG-B) enhances MR1 surface
expression. This is limited to B cells and not other types of cells such as
monocytes, T or natural killer cells. Knocking-down TLR9 expression by short
hairpin RNA reduces MR1 surface expression and MR1-mediated bacterial antigen
presentation. CpG-A triggers early endosomal TLR9 activation, whereas CpG-B is
responsible for late endosomal/lysosomal activation of TLR9. Consistently,
blocking endoplasmic reticulum to Golgi protein transport, rather than lysosomal
acidification, suppressed MR1 antigen presentation. Overall, our results indicate
that early endosomal TLR9 activation is important for MR1-mediated bacterial
antigen presentation.
PMID- 28518217
TI - Impacts of an invasive plant are fundamentally altered by a co-occurring forest
disturbance.
AB - Invasive species frequently co-occur with other disturbances, which can impact
the same ecosystem functions as the invader. Yet invasion studies rarely control
for the presence of these other disturbances, although their overlapping effects
may influence the direction and magnitude of impacts attributed to the invader
alone. Here, we ask whether controlling for the presence of a co-occurring
disturbance, as well as the time since disturbance, yields different values of an
invader's ecosystem effects than when these factors remain unaddressed. We used a
chronosequence of six forest stands at a single site: five logged stands that
each contained paired invaded-uninvaded plots of the forest understory invasive
grass Microstegium vimineum, as well as one unlogged and uninvaded control stand.
By controlling for the presence of both logging and invasion, we untangled the
effects of each through time. We found that the co-occurring disturbance of
logging can dramatically alter the measured effects of M. vimineum by amplifying,
dampening, negating, or entirely reversing the direction of the invader's
impacts. During its period of peak impact, logging amplified the invader's
positive effect on the size of the soil microbial biomass pool by 24%, reduced
the invader's positive effect on soil water holding capacity by 5%, negated the
invader's positive effect on the particulate organic matter carbon pool (from a
9% increase to no significant effect), and reversed the direction of the
invader's impact on net nitrogen mineralization rate from a 51% increase to a 52%
decrease. Furthermore, the influence of logging on the invader's impacts was not
static, but dynamic through time. The results from our site therefore demonstrate
that failure to account for the impacts of a co-occurring disturbance, as well as
the time since disturbance, can result in flawed inference about the nature of an
invader's effects. Future research should determine how widespread such flawed
inference might be among other invasive species and across different
environmental contexts. To help guide such research, we describe a general
framework for disentangling the overlapping effects of invasions and co-occurring
disturbances through time.
PMID- 28518216
TI - Queen presence mediates the relationship between collective behaviour and disease
susceptibility in ant colonies.
AB - The success of social living can be explained, in part, by a group's ability to
execute collective behaviours unachievable by solitary individuals. However,
groups vary in their ability to execute these complex behaviours, often because
they vary in their phenotypic composition. Group membership changes over time due
to mortality or emigration, potentially leaving groups vulnerable to ecological
challenges in times of flux. In some societies, the loss of important individuals
(e.g. leaders, elites and queens) may have an especially detrimental effect on
groups' ability to deal with these challenges. Here, we test whether the removal
of queens in colonies of the acorn ant Temnothorax curvispinosus alters their
ability to execute important collective behaviours and survive outbreaks of a
generalist entomopathogen. We employed a split-colony design where one half of a
colony was maintained with its queen, while the other half was separated from the
queen. We then tested these subcolonies' performance in a series of collective
behaviour assays and finally exposed colonies to the entomopathogenic fungus
Metarhizium robertsii by exposing two individuals from the colony and then
sealing them back into the nest. We found that queenright subcolonies
outperformed their queenless counterparts in nearly all collective behaviours.
Queenless subcolonies were also more vulnerable to mortality from disease.
However, queenless groups that displayed more interactions with brood experienced
greater survivorship, a trend not present in queenright subcolonies. Queenless
subcolonies that engage in more brood interactions may have had more resources
available to cope with two physiological challenges (ovarian development after
queen loss and immune activation after pathogen exposure). Our results indicate
that queen presence can play an integral role in colony behaviour, survivorship
and their relationship. They also suggest that interactions between workers and
brood are integral to colonies survival. Overall, a social group's history of
social reorganization may have strong consequences on their collective behaviours
and their vulnerability to disease outbreaks.
PMID- 28518218
TI - Comparison and optimization of in silico algorithms for predicting the
pathogenicity of sodium channel variants in epilepsy.
AB - OBJECTIVE: Variants in neuronal voltage-gated sodium channel alpha-subunits genes
SCN1A, SCN2A, and SCN8A are common in early onset epileptic encephalopathies and
other autosomal dominant childhood epilepsy syndromes. However, in clinical
practice, missense variants are often classified as variants of uncertain
significance when missense variants are identified but heritability cannot be
determined. Genetic testing reports often include results of computational tests
to estimate pathogenicity and the frequency of that variant in population-based
databases. The objective of this work was to enhance clinicians' understanding of
results by (1) determining how effectively computational algorithms predict
epileptogenicity of sodium channel (SCN) missense variants; (2) optimizing their
predictive capabilities; and (3) determining if epilepsy-associated SCN variants
are present in population-based databases. This will help clinicians better
understand the results of indeterminate SCN test results in people with epilepsy.
METHODS: Pathogenic, likely pathogenic, and benign variants in SCNs were
identified using databases of sodium channel variants. Benign variants were also
identified from population-based databases. Eight algorithms commonly used to
predict pathogenicity were compared. In addition, logistic regression was used to
determine if a combination of algorithms could better predict pathogenicity.
RESULTS: Based on American College of Medical Genetic Criteria, 440 variants were
classified as pathogenic or likely pathogenic and 84 were classified as benign or
likely benign. Twenty-eight variants previously associated with epilepsy were
present in population-based gene databases. The output provided by most
computational algorithms had a high sensitivity but low specificity with an
accuracy of 0.52-0.77. Accuracy could be improved by adjusting the threshold for
pathogenicity. Using this adjustment, the Mendelian Clinically Applicable
Pathogenicity (M-CAP) algorithm had an accuracy of 0.90 and a combination of
algorithms increased the accuracy to 0.92. SIGNIFICANCE: Potentially pathogenic
variants are present in population-based sources. Most computational algorithms
overestimate pathogenicity; however, a weighted combination of several algorithms
increased classification accuracy to >0.90.
PMID- 28518214
TI - Immune monitoring as prerequisite for transplantation tolerance trials.
AB - Ever since its first application in clinical medicine, scientists have been urged
to induce tolerance towards foreign allogeneic transplants and thus avoid
rejection by the recipient's immune system. This would circumvent chronic use of
immunosuppressive drugs (IS) and thus avoid development of IS-induced side
effects, which are contributing to the still unsatisfactory long-term graft and
patient survival after solid organ transplantation. Although manifold strategies
of tolerance induction have been described in preclinical models, only three
therapeutic approaches have been utilized successfully in a still small number of
patients. These approaches are based on (i) IS withdrawal in spontaneous
operational tolerant (SOT) patients, (ii) induction of a mixed chimerism and
(iii) adoptive transfer of regulatory cells. Results of clinical trials utilizing
these approaches show that tolerance induction does not work in all patients.
Thus, there is a need for reliable biomarkers, which can be used for patient
selection and post-therapeutic immune monitoring of safety, success and failure.
In this review, we summarize recent achievements in the identification and
validation of such immunological assays and biomarkers, focusing mainly on kidney
and liver transplantation. From the published findings so far, it has become
clear that indicative biomarkers may vary between different therapeutic
approaches applied and organs transplanted. Also, patient numbers studied so far
are very small. This is the main reason why nearly all described parameters lack
validation and reproducibility testing in large clinical trials, and are
therefore not yet suitable for clinical practice.
PMID- 28518220
TI - Postdonation iron replacement for maintaining iron stores in female whole blood
donors in routine donor practice: results of two feasibility studies in
Australia.
AB - BACKGROUND: Iron deficiency represents a risk to donor health and the blood
supply. Efficacy trials indicate that postdonation iron replacement improves iron
stores but they do not account for complexities of implementation in the routine
collection context. We therefore conducted two prospective feasibility studies in
Australian donor centers. STUDY DESIGN AND METHODS: In both studies we recruited
female donors between 18 and 45 years who had made at least one donation in the
previous 12 months. In READ (replacement advice), female donors were given a
recommendation to self-procure postdonation iron. In DIRECT (donor iron
replacement), donors were provided with a course of iron supplements. Donors
could return to donate at their discretion and were surveyed after the
recruitment visit and again toward the end of the 13-month follow-up. Donor
uptake, adverse effects, effectiveness in maintaining iron stores, and workflow
impact were assessed. RESULTS: We recruited 1404 (70.9% of invited) donors to
READ and 768 (53.2% of invited) to DIRECT. READ and DIRECT extended predonation
interviews by 1 and 5 minutes, respectively. Among participants, 44 and 88% took
iron in READ and DIRECT, respectively. Adverse effects were common but usually
mild. READ failed to maintain iron stores in the population, but was effective in
donors who consumed more than 75% of the recommended dose. DIRECT was effective
in preventing declines in ferritin concentration. CONCLUSION: Trade-offs between
cost, complexity, uptake, and effectiveness must be considered in the
implementation of postdonation iron supplementation.
PMID- 28518219
TI - Impact of the timing of hepatitis B virus identification and anti-hepatitis B
virus therapy initiation on the risk of adverse liver outcomes for patients
receiving cancer therapy.
AB - BACKGROUND: Data on the incidence of adverse liver outcomes are limited for
cancer patients with chronic (hepatitis B surface antigen [HBsAg]
positive/hepatitis B core antibody [anti-HBc]-positive) or past (HBsAg
negative/anti-HBc-positive) hepatitis B virus (HBV) after chemotherapy. This
study was aimed at determining the impact of test timing and anti-HBV therapy on
adverse liver outcomes in these patients. METHODS: Patients with solid or
hematologic malignancies who received chemotherapy between 2004 and 2011 were
retrospectively studied. HBV testing and anti-HBV therapy were defined as early
at the initiation of cancer therapy and as late after initiation. Outcomes
included hepatitis flares, hepatic impairment, liver failure, and death. Time-to
event analysis was used to determine incidence, and multivariate hazard models
were used to determine predictors of outcomes. RESULTS: There were 18,688 study
patients (80.4% with solid tumors). The prevalence of chronic HBV was 1.1% (52 of
4905), and the prevalence of past HBV was 7.1% (350 of 4905). Among patients with
solid tumors, late identification of chronic HBV was associated with a higher
risk of hepatitis flare (hazard ratio [HR], 4.02; 95% confidence interval [CI],
1.26-12.86), hepatic impairment (HR, 8.48; 95% CI, 1.86-38.66), liver failure
(HR, 9.38; 95% CI, 1.50-58.86), and death (HR, 3.90; 95% CI, 1.19-12.83) in
comparison with early identification. Among patients with hematologic
malignancies and chronic HBV, the risk of death was 7.8 (95% CI, 1.73-35.27)
times higher for persons with late initiation of anti-HBV therapy versus early
initiation. Patients with late identification of chronic HBV had late or no anti
HBV therapy. Chronic HBV predicted liver failure in patients with solid or
hematologic malignancies, whereas male sex and late identification were
predictors for patients with solid tumors. CONCLUSIONS: Early identification
correlates with early anti-HBV therapy and reduces the risk of liver failure and
death in chronic HBV patients receiving chemotherapy. Cancer 2017;123:3367-76.
(c) 2017 American Cancer Society.
PMID- 28518225
TI - MO-F-BRA-01: A Biomechanical Constraint for Intensity-Driven Deformable Alignment
of Skeletal Components in the Head and Neck Region.
AB - PURPOSE: To introduce a biomechanical constraint into an intensity-based
deformable image registration (DIR) method in order to limit nonphysical
deformations of skeletal components in the neck region. METHODS: On the reference
image, vertebral bodies were segmented. A penalty term, based on the differences
in squared inter-voxel distances within each vertebra before and after
deformation, was introduced into a routinely used (ITK) intensity-based B-spline
alignment algorithm. To assess accuracy, deformable image registration was
performed on five pairs of cone-beam CT scans of a head and neck cancer patient.
Surface registrations of individual vertebrae established their true
displacements (translations and rotations). Orthogonal Procrustes analysis of
transformed points within each vertebra established the estimated rotations and
translations from the resultant deformation vector fields with and without the
penalty term. RESULTS: The registration errors across all points within the
vertebrae with the penalty term (0.2+/-0.2, 0.2+/-0.2, 0.3+/-0.2) [mm] were
significantly lower than without (2.8+/-2.6, 3.2+/-2.9, 2.8+/-3.0) [mm],
indicating that employing the penalty term successfully restricted local
deformation in the region of the cervical vertebrae. The errors of the bulk
translations and rotations of individual vertebrae were similarly reduced: (0.7+/
0.4, 0.9+/-0.7, 0.5+/-0.4) to (O.1+/-0.1, 0.l+0.1, 0.2+/-0.2) [mm] for
translation and (3.4+/-2.6, 1.3+/-1.1, 1.4+/-1.1) to (0.7+/-0.6, 0.3+/-0.2, 0.3+/
0.3) [ degrees ] for rotation. CONCLUSIONS: The introduction of a local rigidity
penalty improved the integrity of skeletal alignment under neck articulation.
Further research will explore biomechanical penalties that will more
realistically constrain the changes of other tissues (e.g. muscles) in the neck
region. Supported by NIHR01CA59827.
PMID- 28518223
TI - Low shear stress induces endothelial reactive oxygen species via the AT1R/eNOS/NO
pathway.
AB - Reactive oxygen species (ROS) contribute to many aspects of physiological and
pathological cardiovascular processes. However, the underlying mechanism of ROS
induction by low shear stress (LSS) remains unclear. Accumulating evidence has
shown that the angiotensin II type 1 receptor (AT1R) is involved in inflammation,
apoptosis, and ROS production. Our aim was to explore the role of AT1R in LSS
mediated ROS induction. We exposed human umbilical vein endothelial cells
(HUVECs) to LSS (3 dyn/cm2 ) for different periods of time. Western blotting and
immunofluorescence showed that LSS significantly induced AT1R expression in a
time-dependent manner. Using immunohistochemistry, we also noted a similar
increase in AT1R expression in the inner curvature of the aortic arch compared to
the descending aorta in C57BL/6 mice. Additionally, HUVECs were cultured with a
fluorescent probe, either DCFH, DHE or DAF, after being subjected to LSS. Cell
chemiluminescence and flow cytometry results revealed that LSS stimulated ROS
levels and suppressed nitric oxide (NO) generation in a time-dependent manner,
which was reversed by the AT1R antagonist Losartan. We also found that Losartan
markedly increased endothelial NO synthase (eNOS) phosphorylation at
Ser(633,1177) and dephosphorylation at Thr(495), which involved AKT and ERK.
Moreover, the ROS level was significantly reduced by endogenous and exogenous NO
donors (L-arginine, SNP) and increased by the eNOS inhibitor L-NAME. Overall, we
conclude that LSS induces ROS via AT1R/eNOS/NO.
PMID- 28518222
TI - The effect of initial molecular profile on response to recombinant interferon
alpha (rIFNalpha) treatment in early myelofibrosis.
AB - BACKGROUND: Although recombinant interferon-alpha (rIFNalpha) effectively treats
patients with early myelofibrosis, the effect of driver and high molecular risk
(HMR) mutations has not been considered. In this phase 2 study, for the first
time, the authors correlate response to rIFNalpha treatment with driver and HMR
mutations. METHODS: Patients were diagnosed using World Health Organization or
International Working Group for Myeloproliferative Neoplasms Research and
Treatment criteria. Only patients who had low or intermediate-1 Dynamic
International Prognostic Scoring System scores with >=15% hematopoietic bone
marrow foci were included. History, symptom assessment, physical examination, and
blood and bone marrow studies were performed. Genomic DNA was extracted from
frozen cells, and next-generation targeted sequencing of 45 genes was performed.
Either rIFNalpha-2b (0.5 million units subcutaneously 3 times weekly) or
pegylated rIFNalpha-2a (45 MUg weekly) with escalation was initiated. All
patients were followed at the authors' institution, and regular bone marrow
biopsies were encouraged. International Working Group for Myeloproliferative
Neoplasms Research and Treatment and European LeukemiaNet treatment response
criteria were used. RESULTS: Of 30 patients (16 women and 14 men; median age, 58
years), 22 were classified as low risk, and 8 were classified as intermediate-1
risk. Two patients achieved complete remission, 9 achieved partial remission, 4
had clinical improvement, 7 had stable disease; 3 had progressive disease, 1
relapsed, and 4 died. There were 22 patients with JAK mutations, 6 with CALR
mutations, and 2 with MPL mutations. Seventy-three percent of patients improved
or remained stable with acceptable toxicity, including 37% who achieved complete
or partial remission. There was no correlation between treatment response and
baseline driver mutations or Dynamic International Prognostic Scoring System
scores. Of 8 poor responders, 3 had ASXL1 or SRSF2 mutations. CONCLUSIONS: Early
treatment with rIFNalpha in patients without HMR mutations may prevent the
development of marked splenomegaly, anemia, and florid myelofibrosis. Molecular
profiling at the time of diagnosis may predict prognosis and treatment response.
Cancer 2017;123:2680-87. (c) 2017 American Cancer Society.
PMID- 28518226
TI - MO-E-211-01: ABR 2014: Trained for Competence.
AB - : Medical physicists are the only non-physician professionals recognized by the
American Board of Medical Specialties through certification by the American Board
of Radiology (ABR). The ABR has always set high standards of clinical competency
and now with the endorsement of the AAPM, is able to raise these standards by
mandating that in 2014, to sit as a candidate for board certification, enrollment
in an accredited physics residency program is required. This is an enormous step
to elevate our profession, as now we have the means to specify only one method
for achieving board certification that is through an accredited residency
program, which leads to an increase of clinical competency. This will have a
positive impact on our profession's recognition. Most challenges have been met,
namely the number of residency positions has increased exponentially to meet the
manpower needs. In addition, funding mechanisms are being sought for government
support of such training programs. However, we have to ensure that pathways for a
residency and certification do not eliminate strong scientists; if for example,
they do not have the prior educational pre-requisite. Our profession has always,
and must continue to breed strong scientists who have clinical expertise though
may not be seeking a clinical career. This requires developing skill sets that
prepare scientists to be researchers or residents who can perform research. We
will discuss the benefits of the 2014 mandate along with the challenges that
still exist. LEARNING OBJECTIVES: 1. The ABR requirements c2014: Why they're
needed and how they were established 2. Physics Residency Programs: Importance
for our profession and methods to fund 3. Essential elements for competency:
didactic, scientific and clinical.
PMID- 28518227
TI - MO-F-BRCD-02: SBRT (Part 2): Physics and Quality Assurance Updates.
AB - The technical advantage of stereotactic body radiation therapy (SBRT) is based
upon the ability to deliver a hypofractionated course of heterogeneous dose to a
well-defined volume with a rapid fall-off of dose outside the treatment volume.
The overall goal is to deliver an ablative dose to the target while minimizing
the effects of radiation on the surrounding normal tissue. The major advantage of
SBRT is the greater biologically effective dose to the target than that permitted
by less conformal, fractionated techniques. In this presentation the established
recommendations for quality assurance and safety of SBRT from ACR, ASTRO, and
AAPM will be reviewed. The recommendations include establishing an SBRT clinic,
equipment and imaging considerations, overview of staffing and personnel
qualifications, treatment planning considerations, training, acceptance and
commissioning practices, and use of safety checklists. Additionally, a Failure
Mode and Effect Analysis (FMEA) for Stereotactic Body Radiation Therapy Delivery
is presented. References: 1. Timothy D. Solberg PhD, James M. Balter PhD, Stanley
H. Benedict PhD, Benedick A. Fraass PhD, Brian Kavanagh MD, Curtis Miyamoto MD,
Todd Pawlicki PhD, Louis Potters MD, Yoshiya Yamada MD, "Quality and safety
considerations in stereotactic radiosurgery and stereotactic body radiation
therapy" Practical Radiation Oncology (2011)2. Benedict SH, Yenice KM, Followill
D, et al., "Stereotactic Body Radiation Therapy: The Report of AAPM Task Group
101" Med Phys. 2010;37:4078- 41013. Potters L, Kavanagh B, Galvin JM, et al.
American Society for Therapeutic Radiology and Oncology (ASTRO) and American
College of Radiology (ACR) practice guideline for the performance of stereotactic
body radiation therapy. Int J Radiat Oncol Biol Phys. 2010;76:326-3324. Julian R.
Perks PhD, Sinisa Stanic MD, Robin L Stern PhD, Barbara Henk RN MSN, Marsha S
Nelson RN MBA, Rick D Harse RTT, Mathew Mathai BS CMD, James A Purdy PhD, Richard
K Valicenti MD MA, Allan D Siefkin MD and Allen M Chen MD, "Failure Mode and
Effect Analysis for Stereotactic Body Radiation Therapy Delivery" Int J Radiat
Oncol Biol Phys. 2012 (in press) Learning Objectives: 1. Review and understand
the ASTRO Recommendations for QA and Safety with SBRT 2. Review and understand
the AAPM Task Group Recommendations for SBRT 3. Review and understand a FEMA
Analysis of SBRT.
PMID- 28518224
TI - T helper type 1-related molecules as well as interleukin-15 are hyperexpressed in
the skin lesions of patients with pyoderma gangrenosum.
AB - Pyoderma gangrenosum (PG) is a rare, immune-mediated skin disease classified into
the group of neutrophilic dermatoses. Although a number of studies confirmed the
central role of innate immunity, only few studies have investigated the possible
contributing role of acquired immunity. In particular, no reports concerning T
helper type 1 (Th1) and Th2 cells are available as yet. Therefore, 15 patients
with PG, five with Sweet's syndrome (SS) and nine skin specimens from healthy
controls (HC) were investigated, evaluating the expression of Th1-related markers
interleukin (IL)-12, interferon (IFN)-gamma, C-X-C motif chemokine receptor 3
(CXCR3) and C-C motif chemokine receptor 5 (CCR5), of the Th2-related molecules
IL-4, IL-5, IL-13 and CCR3, of the co-stimulatory axis CD40/CD40 ligand, of IL-15
and the natural killer (NK) cell marker CD56 in skin lesions by
immunohistochemistry. Patients with PG and SS showed a higher expression of Th1
markers than HC. Conversely, IL-5- and CCR3-expressing cells were less numerous
in PG skin lesions compared to SS (P = 0.0157 and < 0.0001, respectively). Both
CD40 and CD40L were expressed more in PG than in SS and HC (P < 0.0001 for both).
Finally, the number of IL-15+ and CD56+ cells was higher in the skin of patients
with PG than in those of SS and HC (P < 0.0001 for both). Our results suggest
that Th2 cells are down-regulated in PG. At the same time, over-expression of the
co-stimulatory axis CD40/CD40L amplifies the impairment of the Th1/Th2 balance.
Both these findings might explain the most aggressive behaviour of PG in
comparison to SS. Moreover, over-expression of IL-15+ and CD56+ cells may suggest
a possible role of NK cells in the pathogenesis of the disease.
PMID- 28518221
TI - Micronutrient supplementation in adults with HIV infection.
AB - BACKGROUND: Micronutrient deficiencies are common among adults living with HIV
disease, particularly in low-income settings where the diet may be low in
essential vitamins and minerals. Some micronutrients play critical roles in
maintenance of the immune system, and routine supplementation could therefore be
beneficial. This is an update of a Cochrane Review previously published in 2010.
OBJECTIVES: To assess whether micronutrient supplements are effective and safe in
reducing mortality and HIV-related morbidity of HIV-positive adults (excluding
pregnant women). SEARCH METHODS: We performed literature searches from January
2010 to 18 November 2016 for new randomized controlled trials (RCTs) of
micronutrient supplements since the previous review included all trials
identified from searches prior to 2010. We searched the CENTRAL (the Cochrane
Library), Embase, and PubMed databases. Also we checked the World Health
Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and
the ClinicalTrials.gov trials registers. We also checked the reference lists of
all new included trials. SELECTION CRITERIA: We included RCTs that compared
supplements that contained either single, dual, or multiple micronutrients with
placebo, no treatment, or other supplements. We excluded studies that were
primarily designed to investigate the role of micronutrients for the treatment of
HIV-positive participants with metabolic morbidity related to highly active
antiretroviral therapy (HAART). Primary outcomes included all-cause mortality,
morbidity, and disease progression. DATA COLLECTION AND ANALYSIS: Two review
authors independently selected trials for inclusion, and appraised trial quality
for risk of bias. Where possible, we presented results as risk ratios (RR) for
dichotomous variables, as hazard ratios (HRs) for time-to-event data, and as mean
differences (MD) for continuous variables, each with 95% confidence intervals
(CIs). Since we were often unable to pool the outcome data, we tabulated it for
each comparison. We assessed the certainty of the evidence using the GRADE
approach. MAIN RESULTS: We included 33 trials with 10,325 participants, of which
17 trials were new trials. Ten trials compared a daily multiple micronutrient
supplement to placebo in doses up to 20 times the dietary reference intake, and
one trial compared a daily standard dose with a high daily dose of multivitamins.
Nineteen trials compared supplementation with single or dual micronutrients (such
as vitamins A and D, zinc, and selenium) to placebo, and three trials compared
different dosages or combinations of micronutrients. Multiple micronutrientsWe
conducted analyses across antiretroviral therapy (ART)-naive adults (3 trials,
1448 participants), adults on antiretroviral therapy (ART) (1 trial, 400
participants), and ART-naive adults with concurrent active tuberculosis (3
trials, 1429 participants). Routine multiple micronutrient supplementation may
have little or no effect on mortality in adults living with HIV (RR 0.91, 95% CI
0.72 to 1.15; 7 trials, 2897 participants, low certainty evidence).Routine
supplementation for up to two years may have little or no effect on the average
of mean CD4+ cell count (MD 26.40 cells/mm3, 95% CI -22.91 to 75.70; 6 trials,
1581 participants, low certainty evidence), or the average of mean viral load (MD
-0.1 log10viral copies, 95% CI -0.26 to 0.06; 4 trials, 840 participants,
moderate certainty evidence). One additional trial in ART-naive adults did report
an increase in the time to reach a CD4+ cell count < 250 cells/mm3 after two
years of high dose supplementation in Botswana (HR 0.48, 95% CI 0.26 to 0.88; 1
trial, 439 participants). However, the trial authors reported this effect only in
the trial arm that received multiple micronutrients plus selenium (not either
supplementation alone), which is inconsistent with the findings of other trials
that used similar combinations of micronutrients and selenium.In one additional
trial that compared high-dose multiple micronutrient supplementation with
standard doses in people on ART, peripheral neuropathy was lower with high dose
supplements compared to standard dose (incidence rate ratio (IRR) 0.81, 95% CI
0.7 to 0.94; 1 trial, 3418 participants), but the trial was stopped early due to
increased adverse events (elevated alanine transaminase (ALT) levels) in the high
dose group. Single or dual micronutrientsNone of the trials of single or dual
micronutrient supplements were adequately powered to assess for effects on
mortality or morbidity outcomes. No clinically significant changes in CD4 cell
count (data not pooled, 14 trials, 2370 participants, very low or low certainty
evidence) or viral load (data not pooled, seven studies, 1334 participants, very
low or low certainty evidence), were reported. Supplementation probably does
increase blood concentrations of vitamin D and zinc (data not pooled, vitamin D:
4 trials, 299 participants, zinc: 4 trials, 484 participants, moderate certainty
evidence) and may also increase blood concentrations of vitamin A (data not
pooled, 3 trials, 495 participants, low certainty evidence), especially in those
who are deficient. AUTHORS' CONCLUSIONS: The analyses of the available trials
have not revealed consistent clinically important benefits with routine multiple
micronutrient supplementation in people living with HIV. Larger trials might
reveal small but important effects.These findings should not be interpreted as a
reason to deny micronutrient supplements for people living with HIV where
specific deficiencies are found or where the person's diet is insufficient to
meet the recommended daily allowance of vitamins and minerals.
PMID- 28518228
TI - MO-F-BRA-05: Real-Time 3D Tumor Localization for Lung IGRT Using a Single X-Ray
Projection.
AB - PURPOSE: To study the feasibility of a novel 2D/3D image registration method,
called Projection Metric Learning for Shape Kernel Regression (PML-SKR), in
supporting on-board x-ray imaging systems to perform real-time image-guided
radiation therapy in the lung. METHODS: PML-SKR works in two stages: planning and
treatment. At planning stage, firstly it parameterizes the patient's respiratory
deformation from the patient's treatment-planning Respiratory-Correlated CTs
(RCCTs) by doing PCA analysis on the inter-phase respiratory deformations.
Secondly, it simulates a set of training projection images from a set of deformed
CTs where their associated deformation parameters are sampled within 3 standard
deviations of the parameter's values observed in the RCCTs. Finally, it learns a
Riemannian distance metric on projection intensity for each deformation
parameter. The learned distance metric forms a Gaussian kernel of a kernel
regression that minimizes the leave-one-out regression residual of the
corresponding deformation parameter. At treatment stage, PML-SKR interpolates the
patient's 3D deformation parameters from the parameter's values in the training
cases using the kernel regression with the learned distance metrics. RESULTS: We
tested PML-SKR on the NST (Nanotube Stationary Tomosynthesis) x-ray imaging
system. In each test case, a DRR (dimension: 64*64) of an x-ray source in the NST
was simulated from a target CT for registration. The target CTs were deformed by
normally distributed random samples of the first three deformation parameters. We
generated 300 synthetic test cases from 3 lung datasets and measured the
registration quality by the mTRE (mean Target Registration Error) over all cases
and all voxels at tumor sites. With PML-SKR's registrations, the average mTRE and
its standard deviation are down from 10.89+/-4.44 to 0.67+/-0.46 mm using 125
training projection images. The computation time for each registration is 12.71+/
0.70 ms. CONCLUSION: The synthetic results have shown PML-SKR's promise in
supporting real-time, accurate, and low-dose lung IGRT. This work was partially
supported by Siemens Medical Solutions.
PMID- 28518229
TI - MO-D-BRB-09: Treatment Delivery QA for Online Adaptive Radiation Therapy Based on
Dynamic Machine Information (DMI): A Feasibility Study.
AB - PURPOSE: To implement a quality assurance (QA) system for the treatment delivery
of online adaptive radiation therapy utilizing Dynamic Machine Information (DMI).
MATERIALS AND METHODS: DMI provides the expected/actual MLC leaf-positions,
delivered MU, and beam-on status every 50ms during delivery. In this study a
stream of DMI inputs is simulated by playing back Dynalog information recorded
while delivering a test fluence map (FM). Based on these DMI inputs, the QA
system performs three levels of monitoring/verification on the plan delivery
process: (1) Following each input, actual and expected FMs delivered up to the
current MLC position is dynamically updated using corresponding MLC positions in
the DMI. The magnitude and frequency of pixel-by-pixel fluence differences
between these two FMs are calculated and visualized in histograms.(2) At each
control point, actual MLC positions are verified against the treatment plan for
potential errors in data transfer between the treatment planning system (TPS) and
the MLC controller.(3) Both (1) and (2) can signal beam-hold with a user
specified error tolerance.(4) After treatment, delivered dose is reconstructed in
TPS based on DMI data during delivery, and compared to planned dose. RESULTS: (1)
Efficiency: Average latency from DMI input to the completion of fluence
difference calculation is <1ms.(2) Efficacy: For test FM, transient error in leaf
positions is (-0.07+/-0.28)mm; cumulative errors in delivered fluence is (0.003+/
0.183)% of the maximal fluence. The system can also identify data transfer errors
between TPS and MLC controller. Off-line dose reconstruction and evaluation show
<0.5% dosimetric discrepancy from planned dose distribution for the test FM.
CONCLUSION: This QA system is capable of identifying MLC position/fluence errors
in near real-time, and assessing dosimetric impact of the treatment delivery
process. It is thus a valuable tool for clinical implementation of online
adaptive radiation therapy. (Research partially supported by Varian) Research
partially supported by Varian Medical Systems.
PMID- 28518230
TI - MO-F-213AB-01: Improving Dose Uniformity in Patch-Field Proton Therapy Using Beam
Current Modulation.
AB - PURPOSE: To improve the dose homogeneity in patch-field proton therapy using beam
current modulation. METHODS: MCNPX simulations were performed for various
configurations of the Mevion S250 beamline. Spread-out Bragg peak (SOBP) dose
distributions were calculated, and lateral and distal dose profiles were
extracted for through- and patch-field targets at depths ranging from 5.0 to 27.5
cm. We define 'dose non-uniformity' (DNU) as the difference between the maximum
and minimum dose relative to the prescription observed in a patched dose
distribution. DNU was first calculated for dose distributions combining through
field lateral dose profiles and with patch-field distal dose profiles, assuming a
'standard' delivery with constant beam current. Distal dose profiles were then
optimized using beam current modulation to better complement the lateral dose
profiles when combined into a patched dose distribution. The DNU for optimized
dose distributions was then calculated and compared to the DNU found for standard
delivery. RESULTS: Using standard deliveries, DNU was 10% or less when patching
lateral profiles 12.5-17.5 cm deep. Significantly greater DNU was observed for
patches outside of this range, sometimes exceeding 35%. Using optimized distal
profiles, DNU was reduced to 10% or less for all lateral profiles deeper than
12.5 cm. Patches with lateral profiles shallower than 12.5 cm were not improved,
as distal dose dropoff could not be improved to better match the sharp lateral
dose dropoff. CONCLUSIONS: Optimizing beam current modulation can create distal
profiles with more gradual dose falloff than found in a standard delivery,
allowing optimized distal dose distributions to sum more homogeneously with
lateral dose distributions. Thus, the hot or cold spots that often appear in
patched dose distributions from standard deliveries can be mitigated by
optimizing beam current. This method may also be applied to feathering methods or
scanned beam deliveries to further improve patch-field dose homogeneity.
Partially supported by MEVION Medical Systems, Inc.
PMID- 28518231
TI - MO-A-218-01: CT Protocol Review - Practical Tips for Imaging Physicists.
AB - In the 1980's and 90's, when every mammography department had a wet film
processor and a sundial to keep the schedule, medical physicists performing
mammography surveys were primarily focused on measuring machine performance and
image quality. As our professional experience matured, medical physicists began
to learn that they were uniquely qualified to help to recommend technique factors
that would balance dose and image quality. Technique charts using different kVp,
target-filter combinations and AEC modes gradually became common and patients
benefitted from our input. With the revolutionary change in CT Scanner technology
and utilization, medical physicists have begun to contribute their expertise to
developing and improving CT protocols. This presentation will present practical
challenges and offer some directions for the practicing medical physicist who
desires to participate in this critical and emerging aspect of imaging physics
practice: CT Protocol Review.
PMID- 28518232
TI - MO-F-BRB-04: Fast Estimation of Secondary Particle Therapy Dose Using a Modified
Track Repeating Method.
AB - PURPOSE: Charged particle beams are of great interest, because they can achieve
highly conformal radiation dose distributions. Despite this, some scattered
radiation is inevitably present outside of the target volumes, and is of concern
because of risks such as radiogenic cancer. Accurately calculating the secondary
dose in regions far from the target volume is very difficult due to extremely low
particle fluence and the effect of heterogeneities on particle ranges, making
calculations possible only with CPU-week long Monte Carlo runs. By using a
modified track repeating method, we demonstrate fast and accurate estimation of
secondary dose appropriate for clinical use. METHODS: Primary and secondary
particle track databases (including protons, electrons, photons, neutrons, and
positrons) were generated with the Geant4 Monte Carlo toolkit. Several new
strategies were developed or employed to improve the performance of non- primary
particle propagation, including: (1) processing the databases such that only
primary tracks producing deep penetrating photons or neutrons were kept and
particles falling below transport thresholds were discarded, (2) a search
algorithm that can locate a sub-track for a given energy in constant time, (3)
multiplying photon and neutron tracks during propagation and scoring using
particle 'splitting1. RESULTS: Performance and accuracy were benchmarked against
full Monte Carlo calculations (Geant4 and FLUKA). Filtering out tracks that did
not produce deep penetrating photons or neutrons did not affect the accuracy of
the secondary dose calculation. Preliminary performance analysis indicated 60-
100X speed up over Fluka and 700-1000X speed up over Geant4 with well maintained
accuracy. CONCLUSIONS: Estimation of secondary dose from particle therapy has so
far been largely an academic exercise. This method for fast estimation of
secondary dose brings patient / plan specific information within reach, allowing
clinicians to make informed decisions on the potential long-term risks associated
with specific dose delivery plans. Partial funding from NSF grant CBET-0853157.
PMID- 28518233
TI - MO-D-BRB-02: The Radiological Physics Center's Quality Audit Program: Where Can
We Improve?
AB - PURPOSE: To analyze the findings of the Radiological Physics Center's (RPC) QA
audits of institutions participating in NCI sponsored clinical trials. METHODS:
The RPC has developed an extensive Quality Assurance (QA) program over the past
44 years. This program includes on-site dosimetry reviews where measurements on
therapy machines are made, records are reviewed and personnel are interviewed.
The program's remote audit tools include mailed dosimeters (OSLD/TLD) to verify
output calibration, comparison of dosimetry data with RPC 'standard' data,
evaluation of benchmark and patient calculations to verify the treatment planning
algorithms, review of institution's QA procedures and records, and use of
anthropomorphic phantoms to verify tumor dose delivery. The RPC endeavors to
assist institutions in finding the origins of any detected discrepancies, and to
resolve them. RESULTS: Ninety percent of institutions receiving dosimetry
recommendations has remained level for the past 5 years. The most frequent
recommendations were for not performing TG-40 QA tests, wedge factors, small
field size output factors and off-axis factors. Since TG-51 was published, the
number of beam calibrations audited during visits with ion chambers, that met the
RPC's +/-3% criterion, decreased initially but has risen to pre-TG-51 levels. The
OSLD/TLD program shows that only ~3% of the beams are outside our +/-5% criteria,
but these discrepancies are distributed over 12-20% of the institutions. The
percent of institutions with i,3 l beam outside the RPC's criteria is
approximately the same whether OSLD/TLD or ion chambers were used. The first time
passing rate for the anthropomorphic phantoms is increasing with time. The
prostate phantom has the highest pass rate while the spine phantom has the
lowest. CONCLUSIONS: Numerous dosimetry errors continue to be discovered by the
RPC's QA program and the RPC continues to play an important role in helping
institutions resolve these errors. This work was supported by PHS grants CA10953
and CA081647 awarded by NCI.
PMID- 28518234
TI - MO-D-213CD-01: Cartesian Methods for Rapid Time-Resolved MR Angiography.
AB - : The physics of the MR image formation fundamentally trades off spatial
resolution with temporal resolution. Time spent in acquiring data for the second
image of a time series can alternatively be spent in sampling higher spatial
frequencies for the first image to improve its spatial resolution. Historically
this tradeoff has been addressed by making the k-space sampling rate high, such
as with very short repetition times, and with methods such as view sharing in
which only a portion of k-space is updated from one image to the next in a time
series. Over a decade ago the method of parallel acquisition was proposed in
which the signals detected by the individual elements comprising a multi-element
receiver coil are used to provide further spatial discrimination and reduce
acquisition time. These approaches include those based in image space (SENSE) or
in k- space (SMASH, GRAPPA). In the last decade these methods have been
integrated in contrast-enhanced MRA (CE-MRA) to provide a radical improvement in
performance. CE-MRA is an application particularly well suited to these methods.
The general desire for MRA images to be three-dimensional allows the use of 2D
implementation of parallel acquisition, generally much more robust than 1D
implementation. Also, the SNR loss associated with parallel acquisition is
tempered in CE-MRA because high, arterial-phase signal is sampled throughout the
data acquisition. Cartesian MR data acquisition, performed along a rectilinear
sampling pattern in k-space, offers specific advantages in relative ease of
implementation of 2D parallel acquisition and in "freezing" the status of the
time-varying object at a specific timepoint by use of centric view ordering. This
presentation will provide a review of these methods and how they have been
effectively developed and integrated within the last decade for improved time
resolved MRA. Cartesian k-space sampling patterns can now be quickly selected on
a patient- and anatomy-specific basis for optimum acceleration. Receiver coil
arrays have been adapted to allow up to 20* reduction in the number of k-space
points sampled for a given spatial resolution. Reconstruction hardware now allows
generation of 3D images within only hundreds of msec after data acquisition,
permitting real-time generation of diagnostic quality images and their use in
interactively guiding other processes. LEARNING OBJECTIVES: 1. Understand
recently developed physics techniques which have allowed a 20x improvement in the
speed of data acquisition for MR angiography 2. Understand how Cartesian sampling
of k-space facilitates the practical and effective implementation of these
techniques 3. Show how contemporary implementation of these physics techniques
has provided a significant improvement in MRA image quality over the last decade.
PMID- 28518235
TI - MO-C-BRCD-02: Physics of Cancer Cell Migration.
AB - Two-dimensional (2D) in vitro culture systems have for a number of years provided
a controlled and versatile environment for the study of cell adhesion and
migration, two interrelated cell functions critical to cancer metastasis.
However, the organization and functions of focal adhesion proteins in cells
embedded in physiologically more relevant 3D matrices is qualitatively and
functionally different from their organization and functions on conventional 2D
planar substrates. In a 3D, crosslinked, fibrillar collagen matrix, cell
migration and protrusion activity are still regulated by focal adhesion proteins,
such as pl30Cas, FAK, Zyxin, Vinculin, Talin, and VASP, but differently from the
2D case. This talk will describe the implications of the dependence of focal
adhesion rotein-based cellular functions on microenvironmental dimensionality in
cancer. We will discuss the implications of this work in cancer metastasis.
PMID- 28518236
TI - MO-D-BRB-06: JUNIOR INVESTIGATOR WINNER - Fast and Accurate Patient Specific
Collision Detection for Radiation Therapy.
AB - PURPOSE: To develop a fast and generalizable method which can identify all
possible hardware collisions specific to a given patient setup before treatment
planning. METHODS: An anthropomorphic phantom placed in a typical breast setup
using a wingboard was simulated on a CT scanner and the phantom body contour,
table, and gantry geometry were made into polygon meshes using 3D modeling
software. In the treatment room, a limited physical search of the collision
positive zones was performed using the positioned phantom. A software tool that
incorporated a generalized hierarchical bounding box (HBB) collision detection
algorithm was developed and used to virtually map out the entire collision space
by transforming the positions of the polygonal geometry over a given parameter
range. RESULTS: The geometry containing 47K polygons was mapped over a space of
6480 states with an average transform/collision check of 5.5ms, for a total time
of 35.6s on a 3.14GHz dual core computer with 4GB memory. The computed collision
space, using receiver operating curve analysis had an accuracy of 96.35%, and a
positive predictive value of 91.2%. CONCLUSIONS: This work demonstrates a
framework that can provide a fast and accurate map of the collision free space
specific to any patient setup. Differences in physical and simulated collision
space is attributed to inaccuracies of the geometrical models used. Future work
includes improving the efficiency of the algorithm, enhancing the geometrical
models and increasing the dimensions of the search.
PMID- 28518237
TI - MO-D-217A-01: Optimizing Dose in the Interventional Suite: Do You Really Need
That Image Quality?
AB - : The imaging equipment used to guide interventions has evolved significantly in
the recent past. As a result, the equipment has become more complex to operate.
This evolution has left many operators ill equipped to fully optimize the
radiation dose delivered, as they are often more focused on the technical skills
required to complete the case rather than balancing image quality and radiation
dose. In addition, they are usually better trained in these technical skills than
in the delivery of optimal dose. Interventionalists are faced with dose
optimization in two main venues: the angiography suite and the CT suite. In the
angiographic suite, the operator has the ability to manipulate very simple
parameters which can optimize dose. These, in combination with geometric and
protective barrier techniques, can create a safe and efficient environment for
patients, staff and operators. In addition, with the assistance of a medical
physicist, operators can become more facile with their equipment and help to
develop local protocols for their institution. In the CT suite, a similar
approach can be applied. While the operator is more dependent on the technologist
to manipulate the parameters during a case, the two can work together to optimize
the dose for CT-guided procedures. Knowledge of the key variable parameters is
paramount to developing this team approach. This course will review simple
techniques that operators can employ to optimize dose during both
fluoroscopically- and CT- guided procedures, and will examine the question, "Do
you really need that image quality?" LEARNING OBJECTIVES: 1. Gain a better
appreciation of the clinical perspective and need for operator education. 2.
Identify simple techniques which can be employed to optimize dose with both
fluoroscopically- and CT-guided interventions. 3. Discuss the importance of the
question, "Do you really need that image quality?"
PMID- 28518238
TI - MO-A-213CD-01: CT QC Testing Under the Draft ACR QC Manual.
AB - : There are many recommendations for appropriate quality control for computed
tomography scanners. The breadth of the recommendations is large and this has led
to confusion as to what quality control is indeed necessary. The American College
of Radiology is producing a QC Manual for CT under the auspices of the CT
Accreditation Program. The draft manual is currently under final stages of
review. LEARNING OBJECTIVES: 1. Review current recommendations for CT quality
control 2. Describe the draft QC program of the ACR CT QC Manual 3. Discuss the
status of the ACR CT QC Manual.
PMID- 28518239
TI - MO-D-218-03: ACR Ultrasound Practice Accreditation and Technical Standard for
Ultrasound Performance Monitoring.
AB - : The first part of this presentation will provide an overview of the American
College of Radiology (ACR) Technical Standard for Diagnostic Medical Physics
Performance Monitoring of Real Time Ultrasound Equipment, as well as the ACR
Accreditation requirements for general and breast ultrasound practices. The
second part of the will discuss practical aspects of implementing QC programs
that satisfy the requirements of the ACR practice accreditation programs,
including consideration of personnel roles, and performance testing schedules,
specific methods, and available tools. LEARNING OBJECTIVES: 1. Understand the ACR
Technical Standard for Diagnostic Medical Physics Performance Monitoring of Real
Time Ultrasound Equipment, and the QC requirements of the ACR Ultrasound and
Breast Ultrasound Practice Accreditation Programs 2. Be able to implement
ultrasound QC programs in keeping with these documents.
PMID- 28518241
TI - MO-F-BRA-04: Voxel-Based Statistical Analysis of Deformable Image Registration
Error via a Finite Element Method.
AB - Purpose Clinical implementation of adaptive treatment planning is limited by the
lack of quantitative tools to assess deformable image registration errors (R
ERR). The purpose of this study was to develop a method, using finite element
modeling (FEM), to estimate registration errors based on mechanical changes
resulting from them. Methods An experimental platform to quantify the correlation
between registration errors and their mechanical consequences was developed as
follows: diaphragm deformation was simulated on the CT images in patients with
lung cancer using a finite element method (FEM). The simulated displacement
vector fields (F-DVF) were used to warp each CT image to generate a FEM image. B
Spline based (Elastix) registrations were performed from reference to FEM images
to generate a registration DVF (R-DVF). The F- DVF was subtracted from R-DVF. The
magnitude of the difference vector was defined as the registration error, which
is a consequence of mechanically unbalanced energy (UE), computed using 'in-house
developed' FEM software. A nonlinear regression model was used based on imaging
voxel data and the analysis considered clustered voxel data within images.
Results A regression model analysis showed that UE was significantly correlated
with registration error, DVF and the product of registration error and DVF
respectively with R2=0.73 (R=0.854). The association was verified independently
using 40 tracked landmarks. A linear function between the means of UE values and
R- DVF*R-ERR has been established. The mean registration error (N=8) was 0.9 mm.
85.4% of voxels fit this model within one standard deviation. Conclusions An
encouraging relationship between UE and registration error has been found. These
experimental results suggest the feasibility of UE as a valuable tool for
evaluating registration errors, thus supporting 4D and adaptive radiotherapy. The
research was supported by NIH/NCI R01CA140341.
PMID- 28518240
TI - MO-F-BRCD-01: Stereotactic Body Radiation Therapy: Updates on Clinical,
Biological, and Physics/QA:SBRT (Part 1): Biological and Clinical Updates.
AB - Stereotactic Body Radiation Therapy (SBRT) is an important form of cancer therapy
with increasingly broad application across a spectrum of tumor types in primary
and metastatic settings. In this presentation the radiation biology, clinical
experience from various trials, and cautionary updates on normal tissue
tolerances will be presented. The effective radiobiology of SBRT and
hypofractionated courses of therapy has become more evident with the increasing
reports of retrospective clinical outcomes and prospective clinical trial
results. Current open multi-institutional national cooperative trials will be
reviewed. Accumulating clinical experiences are yielding new insights into
practical aspects of tumor and normal tissue responses to high dose per fraction
treatment. Indeed, SBRT has produced profound tumoricidal and ablative effects,
however there is potential for grave toxicity and this demands that clinicians be
knowledgeable regarding normal tissue tolerances for various hypofractionated
courses. As a final note, the technology associated with SBRT has evolved
remarkably in the last decade, and procedures that originally required hours to
plan, with cumbersome quality assurance methods, arduous set-up times, and long
protracted deliveries can now be performed in ever shorter time periods. Given
these technology improvements and recognizing the great palliative potential of
hypofractionated radiation therapy to relieve cancer symptoms quickly and
efficiently, a new strategy to deliver SBRT in a single session called STAT RAD
is presented for discussion.
PMID- 28518242
TI - MO-F-211-01: Methods for Completing Practice Quality Improvement (PQI).
AB - : Practice Quality Improvement (PQI) is becoming an expected part of routine
practice in healthcare as an approach to provide more efficient, effective and
high quality care. Additionally, as part of the ABR's Maintenance of
Certification (MOC) pathway, medical physicists are now expected to complete a
PQI project. This session will describe the history behind and benefits of the
ABR's MOC program, provide details of quality improvement methods and how to
successfully complete a PQI project. PQI methods include various commonly used
engineering and management tools. The Plan-Do-Study-Act (PDSA) cycle will be
presented as one project planning and implementation tool. Other PQI analysis
instruments such as flowcharts, Pareto charts, process control charts and
fishbone diagrams will also be explained with examples. Cause analysis, solution
development and implementation, and post-implementation measurement will be
presented. Project identification and definition as well as appropriate
measurement tool selection will be offered. Methods to choose key quality metrics
(key quality indicators) will also be addressed. Several sample PQI projects and
templates available through the AAPM and other organizations will be described.
At least three examples of completed PQI projects will be shared. LEARNING
OBJECTIVES: 1. Identify and define a PQI project 2. Identify and select
measurement methods/techniques for use with the PQI project 3. Describe
example(s) of completed projects.
PMID- 28518243
TI - MO-A-217A-02: Prostate and Pelvic Lymph Node Anatomy for Contouring.
AB - : Three-dimensional image guided radiotherapy requires familiarity with axial
anatomy of human body to facilitate accurate contouring of target volume for
radiotherapy treatment planning. In this session we will review the axial anatomy
of male pelvis using images from the visible human project. There will be a
review of the literature on how the contour guidelines were formulated and their
clinical application on a CT image set. LEARNING OBJECTIVES: 1. Know the common
anatomical landmarks in pelvis used for contouring. 2. Know the contouring
guidelines used in published contouring atlas. 3. Know how to use the contouring
guidelines in the clinic.
PMID- 28518244
TI - MO-F-BRB-03: A Method to Assess the Need for Clinical Monte Carlo Dose
Calculations for Small Proton Therapy Fields.
AB - PURPOSE: Due to multiple Coulomb scattering in complex geometries, small field
dosimetry in proton therapy is challenging. Our goal was to define an indicator
for the accuracy of dose delivery based on analytical dose calculations in
treatment planning systems for small (e.g. radiosurgery) proton therapy fields.
METHODS: Seven patients whose treatment involved one or more small fields (below
~3.6cm in diameter) were selected. We developed a fast methodology to quantify
the inhomogeneity of the tissue traversed by a single beam using a heterogeneity
index (HI). The implementation was based on the dose calculation approach taken
by our pencil beam algorithm. Plans created with the treatment planning system
were verified against Monte Carlo dose calculations on a field- by-field basis.
DVHs were analyzed and differences in the dose to the GTV were assessed. The
correlation between the HI-values and the discrepancies between planning system
and Monte Carlo in terms of absolute dose to the target was studied. RESULTS: Our
treatment planning system overestimates the dose within the GTV for very small
fields by up to ~8%, even if proper output factor normalization is done in water.
The differences are strongly correlated to HI (Spearman's rho=0.8, rho<0.0001).
More complex heterogeneities within the beam path caused larger errors by the
analytical algorithm. With the established correlation a threshold for the HI can
be set by choosing a tolerance level. CONCLUSIONS: The HI as defined in this
study appears to be a good indicator of the accuracy of proton field delivery in
terms of GTV prescription dose when small fields are being delivered. Each HI
value was obtained in less than 2 minutes allowing implementation of the HI
algorithm in clinical routine. For HI- values exceeding a certain threshold,
either a change in beam incidence or a Monte Carlo dose calculation should be
considered.
PMID- 28518245
TI - MO-D-BRB-01: Accuracy Requirements and Uncertainties in Radiation Therapy: A
Preview of an Upcoming IAEA Report.
AB - PURPOSE: The International Atomic Energy Agency (IAEA) has a mandate 'to
accelerate and enlarge the contribution of atomic energy to peace, health and
prosperity throughout the world'. Through its Human Health Division, this is done
by developing guidance documents on standards of practice in radiation medicine.
In recent years, there have been major advances in the technology of radiation
oncology which have allowed for a transition from conventional 2-D radiation
therapy to the implementation of 3-D conformal radiation therapy (CRT), intensity
modulated radiation therapy (IMRT), image-guided radiation therapy (IGRT),
adaptive radiation therapy (ART), and 4-D imaging and motion management in
radiation therapy. Brachytherapy procedures have also evolved both for high dose
rate (HDR) techniques as well as permanent implants, especially for prostate
cancer treatments. Multiple imaging modalities are now available for target
volume and normal tissue delineation for radiation treatment planning both for
external beam radiation therapy and brachytherapy. With these new advanced
technologies and improved outcome considerations for both external beam and
brachytherapy, there is also a recognized need for greater accuracy in the
radiation treatment process. METHODS: While a number of reports and publications
have defined accuracy needs in radiation oncology, most of these reports were
developed in an era with different radiation technologies and date back to the
1980s and 90s. RESULTS: In view of the new technologies and techniques,
improvements in dosimetry methodologies and new clinical dose- volume data, the
IAEA is developing a new international guidance document on 'Accuracy
Requirements and Uncertainties in Radiation Therapy' in order to reduce these
uncertainties to provide more effective and safer patient treatments.
CONCLUSIONS: This review will summarize the new IAEA report which is expected to
be published later in 2012. This work is supported by the International Atomic
Energy Agency.
PMID- 28518246
TI - MO-D-BRA-01: Limits of Dose Reduction in CT: Where are They and How Will We Know
When We Get There?
AB - : Radiation Dose continues to be a concern with respect to all diagnostic imaging
using ionizing radiation, but especially so with CT imaging. We have always known
how to reduce radiation dose in CT - for example, simply turning down the system
output (e.g. reduce mAs). What we have not been able to do is to simultaneously
reduce dose and maintain "diagnostic image quality". Many recent technical
developments have appeared, and will continue to appear, that will allow users to
reduce radiation dose in CT while "maintaining image quality". However, this last
term is ill-defined and current metrics of image quality are not very applicable
to actual clinical practice. The purpose of this symposium is to: (a) describe
several current and possible future radiation dose reduction methods and the
magnitude of their potential for dose reduction, (b) some description of what
"diagnostic image quality" means, the effects that dose reductions methods have
on this property, description of some metrics that may help us assess this
property quantitatively and this information can be used to guide how low
radiation doses can be reduced. LEARNING OBJECTIVES: 1. Understand both
conventional and emerging radiation dose reduction methods in CT. 2. Understand
the implications on diagnostic image quality for each radiation dose reduction
method. 3. Understand some of the issues in evaluating how much radiation dose
can be reduced and still accomplish a diagnostic imaging task.
PMID- 28518248
TI - MO-C-BRCD-01: Towards Personalized Medicine: Integration of Imaging into Therapy.
AB - : A significant advance in cancer therapy is currently underway with the
evolution from a population-based to a personalized patient-based prescription.
Rapid developments in imaging, particularly adoption of molecular imaging, offer
unprecedented opportunities for accurate characterization of tumor biology, as
well as early assessment of treatment response. Accurate characterization of
tumor biology enables effective selection of appropriate therapy or even a design
of purposefully non-uniform tumor-specific treatment plans, tailored to the
spatial distribution of biological properties of each patient's tumor. Early
assessment of treatment response enables treatment adaptation, potentially
intensifying or reducing the treatment dose to provide more efficacious and less
toxic therapies. However, integration of imaging into therapeutic applications
requires a high level of image quantification, well beyond what is currently
required in diagnostic imaging applications. This lecture will provide an
overview of imaging applications in therapy, ranging from target selection
totreatment response assessment. Potential roadblocks, as well as research
opportunities on the path to personalization of cancer therapy, will be
highlighted. LEARNING OBJECTIVES: 1. Understand the role of imaging in target
definition and treatment response assessment 2. Understand the requirements for
establishing imaging as a biomarker 3. Learn about research opportunities on the
interface between imaging and therapy.
PMID- 28518247
TI - MO-F-213AB-04: Biological Effect of Dose Shadowing by Fiducial Markers in Spot
Scanning Proton Therapy with a Limited Number of Fields.
AB - PURPOSE: In spot scanning proton therapy, accurate patient positioning before and
during treatment is essential. A small gold ball marker is suitable as a fiducial
for prostate treatment. However, it has been pointed out that the marker causes
dose shadowing because the protons are scattered with their energy quickly
diminished. In this research we explore the possibility that the biological
effect of dose shadowing can be mitigated with a limited number of fields.
METHODS: The proton dose distribution in prostate was simulated using Geant4. The
simulations include the Hokkaido University spot scanning nozzle and a water
phantom positioned isocentrically. The PTV was delineated at the center of the
phantom and a gold ball of 2 mm in diameter was placed at the middle of the PTV.
The plan was created by single-field optimization and each of the following beam
arrangements was investigated; (1) single lateral field (2) two lateral fields
(3) two lateral + one anterior fields (4) four-field box. The dose prescription
was D95 = 74 GyE (37 fr). The minimum dose and tumor control probability (TCP)
were compared for the four beam arrangements. RESULTS: For (1)-(4), the minimum
dose values were 55%, 77%, 78%, and 84% of the prescribed dose, respectively. The
reduction of the TCP values from those in the absence of the gold marker were
50%, 2%, 1.1%, and 0.7%, using the TCP model by Wang et al.
(Int.J.Radiat.Oncol.Biol.Phys. 55, 2003) and 2%, 0.7%, 0.5%, and 0.4%, using the
biological parameters in LevegrA1/4n et al. (Int.J.RadiatOncol.Biol.Phys. 51,
2001), respectively. CONCLUSIONS: Although dose shadowing by the gold marker is
locally non-negligible, the size of the affected domain is tiny. It was found
that with a minimum number of fields, the TCP nearly recovers to the value
without the gold marker.
PMID- 28518249
TI - MO-D-BRB-05: An Analysis of 13,000 Patient-Specific IMRT QA Results from 13
Different Clinical Treatment Services.
AB - PURPOSE: To review an institution's patient-specific IMRT quality assurance (QA)
results, including absolute dose and gamma analysis measurements. METHODS:
Patient-specific IMRT QA records were reviewed to obtain information on absolute
dose difference (ion chamber measurement; +/-3% agreement criteria) and
percentage of pixels passing gamma (film measurement; 5%/3 mm agreement criteria)
from 2005 to 2011. The 13,002 plans reviewed, were classified by treatment
service: breast (n=67), central nervous system (n =1383), gastrointestinal
(n=803), genitourinary (n=1831), gynecology (n=935), hematology (n=380), head and
neck (n=3697), intensity-modulated stereotactic spine radiation therapy (n=341),
melanoma (n=54), mesothelioma (n=52), pediatric (n=307), sarcoma (n=201), and
thoracic (n=2951). All records were analyzed for trends according to measurement
date and treatment service. Plans failing to meet QA criteria were further
evaluated for subsequent measured data. RESULTS: Mean difference (+/- one
standard deviation) between the measured and calculated doses was -0.29% +/-
1.64% (with the calculated values being slightly higher). The mean percentage of
pixels passing gamma was 97.7% (lower 95th percentile, 92.2%). The plan pass
rates were 97.7% and 99.3% for absolute dose and gamma, respectively. We observed
statistically significant differences (p < 0.05) in both absolute dose and gamma
measurements as a function of treatment service (particularly for stereotactic
spine and mesothelioma services) and measurement date (average agreement improved
with time). However, despite improved agreement between measured and calculated
doses, the percentage of treatment plans failing to meet the passing criteria has
remained largely constant at ~2.3%. CONCLUSIONS: Our retrospective review of
13,002 patient-specific IMRT QA plans demonstrated that plans continue to fail
IMRT QA criteria at a consistent rate. This rate serves as a clinical reference
for expected rates of QA plan pass and failure for a variety of treatment
services.
PMID- 28518250
TI - MO-D-213CD-04: 4D X-Ray DSA and 4D Fluoroscopy.
AB - : During the past decade the use of undersampled acquisition and constrained
reconstruction have led to significant increases in data acquisition speed, SNR,
spatial resolution and temporal resolution in MR imaging. When a separately
acquired constraining image is combined with an angiographic time series the
traditional tradeoff between spatial and temporal resolution is greatly reduced.
Artifacts and limited resolution that would normally be associated with a rapid
highly undersampled temporal image series are mitigated by the constrained
reconstruction process which transfers the SNR and spatial resolution of the
constraining image to the individual time frames. In rotational C-Arm DSA a 3D
image volume is formed from all the projections acquired during the C-Arm
rotation. Although the individual projections contain temporal information, the
reconstructed 3D image has no temporal information and represents a composite of
the vascular filling that has occurred during the iodine injection. However, the
3D cone beam CT reconstruction can be used to constrain the reconstruction of one
3D volume for each of the rotational projections. This extends the traditional
DSA time series of 2D images to a series of 3D volumes at rates up to 30 per
second. Similar techniques can be used to provide fluoroscopy that can be
embedded in the 3D space of the constraining volume and viewed from arbitrary
angles without gantry motion. This overcomes the problem of forbidden views and
guarantees that an intervention can be done without having to send patients to
surgery. Unlike 4D DSA which requires only one source and receptor, 4D
Fluoroscopy requires a bi-plane fluoroscopy system. LEARNING OBJECTIVES: 1. To
understand the application of under sampling and constrained reconstruction to 4D
DSA and Fluoroscopy.
PMID- 28518251
TI - MO-A-BRA-01: State of the Art in Quantitative Imaging in CT, PET and MRI.
AB - : Diagnostic Imaging is evolving from a modality where the emphasis is on the
acquisition and interpretation of image data by radiologists to one where imaging
devices may be used as measurement devices that are able to produce quantitative
results. Some examples of quantitative measured values are already in clinical
practice, including coronary artery calcium scores from CT, Standard Uptake
Values (SUV) in PET imaging and Diffusion Weighted Imaging (DWI) in MRI. Clinical
and clinical research applications of quantitative anatomical and functional
imaging biomarkers, including those focused on treatment assessment, have
continued to dramatically expand. Studies at single centers have clearly
demonstrated the potential of such applications. However, sources of bias and
variance of quantitative imaging biomarkers have not previously been adequately
investigated, thus limiting the implementation of robust methods to mitigate
their effects. Therefore, when it comes to applications of such techniques across
vendor platforms, centers, and time, challenges arise due to lack of standards,
appropriate phantoms, and protocols. During the past few years, several
quantitative imaging initiatives have been instigated. This symposium
presentation will review selected applications of quantitative imaging
biomarkers, illustrate some of the current challenges in broadening the use of
such biomarkers, and discuss some of the current initiatives of various
scientific and federal organizations that are focused on the standardization,
qualification, and validation of quantitative imaging biomarkers. LEARNING
OBJECTIVES: 1. Understand selected applications of quantitative imaging
biomarkers. 2. Understand the factors that currently limit widespread acceptance
and use of such quantitative imaging biomarkers, including sources of bias and
variance. 3. Understand some of the current initiatives focused on the
standardization, qualification, and validation of selected quantitative imaging
biomarkers. LEARNING OBJECTIVES: 1. Understand selected applications of
quantitative imaging biomarkers. 2. Understand the factors that currently limit
widespread acceptance and use of such quantitative imaging biomarkers, including
sources of bias and variance. 3. Understand some of the current initiatives
focused on the standardization, qualification, and validation of selected
quantitative imaging biomarkers.
PMID- 28518252
TI - MO-D-211-01: Medical Physics Practice Guidelines - The Minimum Level of Medical
Physics Support in Clinical Practice Settings.
AB - : The American Association of Physicists in Medicine (AAPM) has long advocated a
consistent level of medical physics practice, and has published many guidelines
and position statements toward that goal, such as Science Council Task Group
reports related to calibration and quality assurance, Education Council and
Professional Council Task Group reports related to education, training, and peer
review, and Board-approved Position Statements related to the Scope of Practice,
physicist qualifications, and other aspects of medical physicspractice. Despite
these concerted and enduring efforts, the profession does not have a clear and
concise statement of the acceptable practice guidelines for routine clinical
medical physics. As accreditation of clinical practices becomes more common,
Medical Physics Practice Guidelines (MPPGs) will be crucial to ensuring a
consistent benchmark for accreditation programs. The AAPM will lead the
development of MPPGs in collaboration with other professional societies. The
MPPGs will be freely available to the general public. Accrediting organizations,
regulatory agencies and legislators will be encouraged to reference these MPPGs
when defining their respective requirements. MPPGs are intended to provide the
medical community with a clear description of the minimum level of medical
physics support that the AAPM would consider to be prudent in all clinical
practice settings. Support includes but is not limited to staffing, equipment,
machine access, and training. These MPPGs are not designed to replace extensive
Task Group reports or review articles, but rather to describe the recommended
minimum level of medical physics support for specific clinical services. This
course will describe the purpose and scope of MPPGs, the procedure for the
development of a MPPG, as well as the progress of Therapy MPPG TG #1 on
"Evaluation and quality assurance of x-ray based image guided radiotherapy
systems" and Diagnostic MPPG TG #2 on "CT Protocol management and review".
LEARNING OBJECTIVES: 1. Understand the concept and scope of MPPG from the AAPM 2.
Understand the benefits and process of the development of MPPG by the AAPM 3.
Understand the goals and methodology of the Therapy MPPG Task Group #14. 4.
Understand the strategic plans from Professional Council towards the AAPM
initiatives.
PMID- 28518253
TI - MO-D-218-02: Ultrasound Phantoms in Image Quality Measurements and Performance
Assessment.
AB - Agreement has recently emerged for measurement of only three parameters in
routine quality assurance. These include element or channel failure (EOCF),
maximum depth of penetration (MDOP) and distance measurement accuracy (DMA). The
related study leading to this agreement was done at the Mayo Clinic ["Four-year
experience with a clinical ultrasound quality control program," Hangiandreou et
al. Ultrasound Med & Biol, vol. 37, pp. 1350-1357 (2011)]. A variety of phantoms
have been proposed for performing these measurements. These include: 1) a phantom
with both flat and cone-shaped scanning windows, tissue-mimicking material and
parallel nylon fibers for measuring all three parameters; 2) a starch suspension
in water phantom for assessing ECOF; 3) polyurethane phantom for determining ECOF
and estimating MDOP; 4) a silicone phantom for determining ECOF. Determination of
ECOF and MDOP requires acquisition of image cine loops including many
statistically independent versions; analysis of the data requires averaging of
the images in the cine loops, and software is being tested at the time of this
writing for user-friendly downloading and averaging of the cine images. The
phantoms will be described and examples of procedures and results for making
measurements. One method for assessing imaging performance involves quantifying
the detectability of small low-echo spheres as a function of depth; detectability
will depend on sphere size and on depth. It can be argued that the smaller the
sphere and the greater the detectability, the better the scanner can delineate
the boundary of an inclusion such as a spiculated cancer. Phantoms and software
will be described which allow quantitative determination of detectability of low
echo spheres ( 40 dB) as a function of depth; one phantom has a spatially
random distribution of 4-mm diameter low-echo spheres for lower frequencies, and
the other 2-mm diameter spheres for higher frequencies. The parameter that is
quantified is the mean lesion signal-to-noise ratio (LSNR) as described for
cylinders by Lopez H et al. IEEE Trans Med Imaging, 1992 and for spheres by
Kofler et al. Ultrasound Med & Biol, 2005. The phantoms accommodate any size and
shape transducer. Note that spheres have no preferred orientation; therefore,
phased arrays and convex (curved) arrays with a broad range of radii of curvature
and sector angles can be can be assessed. Phantoms for assessing other aspects of
performance such as quantitative determination of the contrast of large objects
in a background will also be discussed.
PMID- 28518254
TI - MO-F-213AB-06: Experimental Evaluation of Radiation Dose Effect by High Atomic
Number Materials for Superficial Radiation Therapy.
AB - PURPOSE: High atomic number (Z) materials have been considered as a method for
enhancing radiation dose in tumors. The dose enhancement due to interactions of
kilovoltage x-rays with high-Z materials (i.e., gold or iodine) has been well
demonstrated through computational works. This study is to experimentally
quantify the effect using gold nanoparticles (AuNPs) and iodine solutions,
respectively. METHOD AND MATERIALS: Iodine and AuNPs (AuroVist, Nanoprobes,
Yaphank NY) are uniformly distributed in each cylinder phantom (1.6 cm diameter
and 2.0 cm depth) separately. Concentrations of Iodine and AuNPs were varied from
40 to 225 mg/ml and 16.0 mg/ml to 42.7 mg/ml, respectively. The Iodine solutions
were irradiated with 75 to 150 kVp x-rays from a superficial x-ray therapy
machine at doses of 250 to 400 cGy. The AuNPs solutions in the cylinder were
irradiated with 40 to 150 kVp x-rays. The phantom was placed at the center of the
cone to ensure a uniform radiation field. Radiation doses were measured using
GafChromic EBT2 films (International Specialty Products, Wayne NJ). Dose
enhancement factors (DEF), i.e., the ratio of dose to high-Z material versus dose
to water, were calculated and plotted as functions of concentration and kVp.
RESULTS: Experimental DEFs varied between 1.01 and 1.38. The DEFs increased with
increasing concentration and varied with changing kVp. The maximum DEF measured
for Iodine solution was 1.38 at 225 mg/ml and 150 kVp. The maximum DEF measured
for AuNPs was 1.22 at 42.7 mg/ml and 40 kVp. The target volume covered by dose
enhancement is larger with relatively lower concentrations. CONCLUSIONS: The
magnitude of dose enhancement due to AuNPs and Iodine presence has a dependency
with the concentration and kVp. In clinical applications, the concentration of
the high-Z material and kVp should also be selected to suit the depth and volume
of the target tumor.
PMID- 28518256
TI - MO-E-217A-01: Contrast-Enhanced Spectral Mammography - Physical Aspects and QA.
AB - PURPOSE: To describe the current state of dual energy contrast-enhanced digital
mammography, to discuss those aspects of its operation that require evaluation or
monitoring and to propose elements of a program for quality assurance of such
systems. METHODS: The principles of dual-energy contrast imaging will be
discussed and tools and techniques for assessment of performance will be
described. RESULTS: Many of the elements affecting image quality and dose
performance in digital mammography (eg noise, system linearity, consistency of x
ray output and detector performance, artifacts) remain important. In addition,
the ability to register images can influence the resultant image quality. The
maintenance of breast compression thickness during the imaging procedure and
calibration of the system to allow quantification of iodine in the breast
represent new challenges to quality assurance. CONCLUSION: CESM provides a means
of acquiring new information regarding tumor angiogenesis and may reveal some
cancers that will not be detectable on digital mammography. It may also better
demonstrate the extent of disease. The medical physicist must understand the
dependence of image quality on physical factors. Implementation of a relevant QA
program will be required if the promise of this new modality is to be delivered.
PMID- 28518257
TI - MO-A-217A-01: An Introduction to Contouring - Neck and Thorax.
AB - : In the last decade IMRT and related treatment modes have become de facto, if
not actual standards of care. These modes are heavily dependent on the anatomical
modeling phase of treatment planning. It may in fact be argued that this is the
most important step in the planning process, as the optimization and plan
evaluation will be directly affected by a good or poor anatomical model.
Physicists have increasingly been called upon to do much of this contouring, yet
have traditionally had only a brief formal introduction to anatomy. This session
will provide a brief overview and refresher on two anatomical regions that have
come to be most often treated by IMRT and like modalities. Dr. Jonn Wu will
discuss the contouring of prominent normal structures and target volumes in the
thorax using multiple imaging modalities, and illuminate key concepts in
identifying these structures. Emphasis will be placed on relevance to SBRT. Dr. I
Chow Hsu will discuss the structures in the pelvis relevant to prostatic
treatments, including pelvic lymphatic chains, using CT and the Visible Human
Project. LEARNING OBJECTIVES: 1. To better understand how to identify structures
in the thorax 2. To better understand how to identify structures in the pelvis
relevant to prostate treatments 3. To understand the impact and pitfalls of
different imaging modalities in these anatomical locations.
PMID- 28518258
TI - MO-F-BRB-02: Macro Monte Carlo for Proton Dose Calculation in Different
Materials.
AB - PURPOSE: Although the Monte Carlo (MC) method allows accurate dose calculation
its usage is limited due to long computing time. In order to gain efficiency, a
new macro MC (MMC) technique for proton dose calculations in homogeneous
materials has been developed. METHODS: The macro MC is based on a local to global
MC approach. The local simulations using Geant4 consist of mono-energetic proton
pencil beams (10 to 250 MeV) impinging perpendicularly on slabs of different
thicknesses (1-10 mm) and different materials (water, lung, muscle, adipose,
bone). During the local simulation multiple scattering, ionization, elastic and
inelastic interactions have been taken into account and the physical
characteristics such as lateral displacement and energy loss have been scored for
primary and secondary particles. The scored data from appropriate slabs is then
used for the stepwise transport of the protons in the MMC simulation while
calculating the energy loss along the path between entrance and exit position.
Additionally, ions and neutrons are taken into account for the dose calculation.
In order to validate the MMC, calculated dose distributions using the MMC
transport and Geant4 have been compared for different mono-energetic proton
pencil beams impinging on phantoms with different homogeneous materials. RESULTS:
The agreement of calculated integral depth dose curves is better than 1% or 1 mm
for all pencil beams and materials considered. For the dose profiles the
agreement is within 1% or 1 mm for all energies, depths and materials. The
efficiency of MMC is about 200 times higher than for Geant4. CONCLUSIONS: The
dose comparisons demonstrate that the new MMC results in very accurate and
efficient dose calculations for proton beams in homogeneous materials. In future,
the MMC method will be extended to inhomogeneous situations in order to allow
patient dose calculations for proton beams. This work was supported by Varian
Medical Systems.
PMID- 28518259
TI - MO-D-BRCD-01: Overview of Clinical Dosimetry and Quality Assurance in Proton
Therapy.
AB - : An overview of current status of clinical proton dosimetry is presented.
Absolute dosimetry in proton beams using IAEA TRS 398 and ICRU 59 dosimetry
protocols is presented. An overview of the use of various detectors for proton
therapy beam characterization is presented including Ion Chambers for point
measurements, Multi-Layer Ionization Chambers (MLICs) for percentage depth dose
(PDD) measurements, and other types of detectors such as TLDs and diodes. The use
of ID and 2D commercial arrays for routine dosimetry for performing daily output,
range verification, symmetry, and flatness is also presented. Some of the
challenges in the design and performance of certain detectors related to LET
quenching effects is discussed. The use of film (radiographic and radiochromic)
for various beam QA tasks is discussed. Current status and prospects of 3D
dosimetry for particle therapy is also presented. Specific challenges in quality
assurance with certain beam delivery technologies are also discussed such as
pencil beams, scattered beams, and uniform scanning beams. Proton machine QA
checks such as daily, monthly, and annual QA, as well as patient specific proton
beam QA are presented. LEARNING OBJECTIVES: 1. Understand proton beam dosimetry
protocols 2. Familiarization with proton dosimetry tools and their limitation 3.
Understand the challenges and procedures in proton therapy QA.
PMID- 28518260
TI - MO-D-BRB-11: Out-Of-Field Dose Measurements in Radiotherapy Using Photons and
Particles.
AB - PURPOSE: Within the European project ALLEGRO (grant agreement no. 231965), the
out-of-field dose delivered to a patient when treated with different radiotherapy
modalities was investigated. The study compared the dose distribution during
photon and particle irradiations both in a water and an anthropomorphic phantom
to evaluate the risk of inducing secondary malignancies. METHODS: Two sets of
experiments with standardized conditions were used for a systematic comparison.
In the former, a water phantom was irradiated with a 2D squared field to
characterize the lateral dose fall-off with high spatial resolution. The latter
employed an anthropomorphic phantom treated for a target volume placed at the
center of its head to simulate a brain tumor. The dose was measured in several
planes along the phantom main axis. For both types of experiments the dose was
measured with a PTW diamond detector. Additionally, the use of TLDs and bubble
detectors provided some information on the secondary neutron field produced both
in the accelerator structure and the target itself. In total, experiments were
conducted at six facilities using photons, protons and carbon ions; the ion
irradiations were performed with passive delivery and the scanning technique.
RESULTS: A significant difference among the out-of-field dose profiles is
observed for distances larger than 3 cm to the target. The distribution delivered
by photons is a factor 10 to 400 higher than the values of charged particles.
Scanning ions reduces the out-of-field dose more than passive delivery at
distances larger than 10 cm. CONCLUSIONS: The study emphasizes the physical
advantage of using charged particles for tumor therapy. Together with the
favorable depth dose deposition, ions spare the normal tissue surrounding the
target more efficiently than photons. These results imply a lower risk of long
term effects, such as the induction of secondary malignancies, following
treatments with particles compared to photons. This work was funded by the
European ALLEGRO project (Grant Agreement No. 231965).
PMID- 28518261
TI - MO-F-213AB-03: Potential Reduction in Out-Of-Field Dose in Pencil Beam Scanning
Proton Therapy Through Use of a Patient-Specific Aperture.
AB - PURPOSE: Patient specific apertures are commonly employed in passive double
scattering (DS) proton therapy (PT). This study was aimed at identifying the
potential benefits of using such an aperture in pencil beam scanning (PBS).
METHODS: An accurate Geant4 Monte Carlo model of the PBS PT treatment head at
Massachusetts General Hospital (MGH) was developed based on an existing model of
the passive double-scattering (DS) system. The Monte Carlo code specifies the
treatment head at MGH with sub-millimeter accuracy and was configured based on
the results of experimental measurements performed at MGH. This model was then
used to compare out-of-field doses in simulated DS treatments and PBS treatments.
The PBS treatments were simulated both with and without the patient-specific
aperture used in the DS treatment. RESULTS: For the conditions explored, a
typical prostate field, the lateral penumbra in PBS is wider than in DS, leading
to higher absorbed doses and equivalent doses adjacent to the primary field edge.
For lateral distances greater than 10cm from the field edge, the doses in PBS
appear to be lower than those observed for DS. Including an aperture at nozzle
exit reduces the penumbral width by preventing wide-angle scatter from reaching
the patient. This can reduce the dose in PBS for lateral distances of less than
10cm from the field edge by over an order of magnitude and allow better dose
conformity. CONCLUSIONS: Placing a patient-specific aperture at nozzle exit
during PBS treatments can potentially reduce doses lateral to the primary
radiation field by over an order of magnitude. This has the potential to further
improve the normal tissue sparing capabilities of PBS. The magnitude of this
effect depends on the beam spot size of the scanning system and is thus facility
dependent.
PMID- 28518262
TI - MO-B-218-01: Managing the Pediatric Patient's CT Dose: The Role of SSDE.
AB - : As many as 6 - 8 million CT scans are performed annually in the United States
on pediatric patients. The majority of these CT scans are not performed in
pediatric hospitals that specialize in addressing the unique requirements of
pediatric imaging. Instead, most of these scans occur in adult hospitals, where
pediatric CT scanning is a small fraction of the total caseload. Both adult and
pediatric hospitals need a simple method that allows the management of the CT
radiation dose received by each patient based on the patient's physical size.
This lecture suggests some simple tools and techniques that the qualified medical
physicist can introduce to an individual practice in an effort to properly manage
CT doses. This lecture begins by exploring the unique challenges presented by the
pediatric patient in the management of their radiation dose during CT scanning.
This is followed by an explanation of the basic science behind the development of
the Size Specific Dose Estimate (SSDE) in CT, the strengths and weaknesses of the
method, and some sample calculations. The presentation concludes by exploring the
clinical application of SSDE in the day to day management of the radiation dose
during CT scanning of not only small pediatric patients, but also patients who
are larger than the average size adult. LEARNING OBJECTIVES: 1. Understand the
basic challenges associated with CT imaging of children. 2. Understand the basic
science used to develop SSDE, its strengths and its limitations 3. Understand the
application of SSDE in the clinic in the daily management of pediatric CT doses.
PMID- 28518263
TI - MO-F-BRB-06: Gold Nanoparticle Modify Density of Ionizations inside Cells
Submitted to Radiation Therapy: Microscopic Track Analysis of Secondary Electrons
Using Monte Carlo.
AB - PURPOSE: Study density of ionization in cells containing gold nanoparticles
(AuNP) submitted to Radiation Therapy. METHODS: Spherical gold nanoparticles with
diameters ranging 0-100nm were considered evenly distributed inside a 20mgr;m
cubic cell, maintaining the gold concentration of 0.01%, with constant number of
gold atoms inside the cell. Monte Carlo simulations were performed using PENELOPE
code considering event-by-event transport of secondary electrons with minimum
energy of 1keV. Simulated clinical energy spectrum of 250kV and 6MV x-rays;Co-60
and Ir-192 gamma-ray sources obtained at each corresponding build-up depths were
considered. Density of ionization inside the cell was evaluated counting delta
electrons created either in AuNP or cell, excluding electrons attenuated inside
the nanoparticles. The dose enhancement resultant from interaction of electrons
with few micrometers range was quantified by the factor MUDEF as the ratio of
doses inside the cell with and without AuNP. RESULTS: Maps of ionization density
were obtained at the central plane of the cell illustrating ionizations around
and between AuNP. The density of ionization increases in cell medium as the AuNP
diameter enlarges, being higher to larger nanoparticles for all energies studied.
The total dose deposited in the cell is affected by the fraction of electrons
consumed in the nanoparticles, resulting in size-dependence for MUDEF. The MUDEFs
for 250kV are 1.68 to 20nm, 1.83 to 60nm and 1.72 to 100nm; MUDEFs for 6MV are
1.14 to 20nm, 1.38 to 60nm and 1.20 to 100nm, therefore presenting an optimum
nanoparticle size for clinical applications in Radiation Therapy. CONCLUSIONS:
The MUDEF describes dose enhancements founded on the effective density of
ionizations inside cell medium containing AuNP, considering real electron tracks
close to metallic interfaces. The profile of ionizations describes electron
spectra of electrons with intracellular range considering dynamics of creation
and consumption, hence being directly proportional to potential applicability of
AuNP in Radiation Therapy. This work was funding supported by CAPES - Nanobiomed
Network.
PMID- 28518264
TI - MO-D-BRB-04: The Approval Process for the Use of Proton Therapy in NCI-Sponsored
Clinical Trials.
AB - PURPOSE: To describe the approval process for the use of proton therapy in NCI-
sponsored clinical trials. METHODS: The RPC has developed a comprehensive system
for the approval of proton therapy centers for participation in clinical trials.
The approval process includes: 1) completion of the proton facility
questionnaire, 2) participation in the RPC's annual TLD remote audit program, 3)
electronic submission of treatment planning data to the Image-Guided Therapy
Center (ITC), and 4) successful completion of an on-site dosimetry review visit,
including the irradiation of two of the RPC's anthropomorphic proton phantoms
(prostate and spine). The on-site audits allow the RPC to review the
institution's treatment planning process, from simulation to treatment delivery,
as well as their quality assurance practices. The RPC performs a complete set of
measurements that tests the CT simulator's CT# vs. RSP conversion curve,
treatment planning data, on-board imaging, and treatment delivery. These
measurements detect gross errors that might lead to inaccurate proton dose
delivery. The review of the institutions' QA procedures allows the RPC to
encourage all proton centers to maintain a consistent level of periodic
monitoring of their proton therapy delivery. Upon completion of the visit, a full
report is written detailing the results from the visit, phantom irradiation, and
recommendations for improving their treatment delivery and QA. RESULTS: To date,
the RPC has approved seven proton therapy centers for the use of scattered or
uniform scanning proton treatment delivery in clinical trials. Results of the
phantom irradiations have identified an error in the HU vs RLSP curve. The site
visits have identified several lapses in QA procedures, inappropriate HU vs RLSP
values, and weaknesses in treatment planning. CONCLUSIONS: The RPC's proton
therapy approval process has been developed and has identified areas of
improvement for proton centers to use proton therapy in clinical trials. Work
supported by grants CA10953, CA059267, and CA81647 (NCI, DHHS).
PMID- 28518265
TI - MO-D-213CD-03: Advanced Angiographic Imaging Techniques.
PMID- 28518266
TI - MO-A-BRB-04: Treatment Plan Data Collection, Beam Modeling and Clinical
Validation for Unfiattened Beams.
AB - : The use of an unfiattened photon beam for radiotherapy treatment is a new
concept in the Radiation Oncology field. In the past, the non-optimal radiation
area coverage obtained with unfiattened photon beams was of concern, and the
flattening filter was introduced to overcome this pitfall. With the advance of
technology, Intensity Modulated Radiotherapy (IMRT) emerged and non-optimal
coverage was no longer an issue since the beam intensity could be modulated to
obtain the desired target coverage. Unfiattened photon beams offer several
advantages over flattened beams, namely: (1) they provide 2 to 4 times the dose
rate, which significantly shortens the treatment time, especially for the high
dose irradiation techniques, (2) they provide a purer beam spectrum, which is
easier to model in a treatment planning system, (3) the head scatter is
dramatically reduced, giving a lower dose outside of the field and (4) they
provide a sharper penumbra, which makes planning easier. This lecture will
provide an overview of the data collection, the treatment planning system (TPS)
parameter modeling and the TPS validation for clinical implementation of
unfiattened photon beams. LEARNING OBJECTIVES: 1. Understand the physics data
collection and related issues. 2. Understand the TPS parameter modeling, planning
validation and related issues. 3. Understand the optimal usage of unfiattened
beams with clinical examples.
PMID- 28518267
TI - MO-D-217BCD-01: Personalizing Medicine: Adapting to the Individual.
AB - : Personalizing medicine through patient-specific adaptation is quickly moving
from retrospective research to clinical implementation. The commercial
availability of clinical tools, including auto-segmentation, deformable
registration, and dose accumulation, is enabling these techniques to be utilized
more efficiently. Understanding the importance, rationale, and consequences of
anatomical and physiological based adaptation is paramount for the safe
implementation of these techniques. This includes accounting for radiobiological
differences in delivered dose and the impact that this may have on tumor control
and normal tissue response. This interactive session will highlight the evidence
and rationale for anatomy-based adaptation, including retrospective studies from
several anatomical sites indicating the uncertainties between the planned and
delivered dose and the benefits achievable through adaptation. Translation of
these techniques into the clinic will be discussed. The growing use of functional
imaging enables more sophisticated adaptation and personalization of the
treatment plan based on an understanding of the individual response of the tumor
and normal tissue to radiation. Methods to understand and incorporate this
information into the patient treatment plan will be discussed. The
radiobiological impact of dose accumulation methods and adaptive strategies is
often overlooked. Biological factors and their influence on these adaptive
strategies will be addressed. The clinician's perspective will also be
highlighted, including the benefits of dose accumulation, personalization, and
adaptation for the patient and the impact that this technology may have on
clinical trials and outcomes assessment. LEARNING OBJECTIVES: 1. Understand the
need for anatomy-based adaptation and methods to safely implement this in the
clinic 2. Recognize the need for physiological-based adaptation and methods to
safely implement this into the clinic 3. Appreciate the radiobiological
limitations and concerns associated with dose summation, and adaptation 4.
Describe the clinical implications of dose summation and adaptation on individual
patient treatments, clinical trials, and outcomes assessment.
PMID- 28518268
TI - MO-D-BRB-08: BEST IN PHYSICS (THERAPY) - A Real Time Dose Monitoring and Dose
Reconstruction Tool for Patient Specific VMAT QA and Delivery.
AB - PURPOSE: To develop a real time dose monitoring and dose reconstruction tool to
identify and quantify sources of errors during patient specific VMAT delivery and
QAMethods: The VMAT delivery monitor tool called Linac Data Monitor (LDM) has
been developed that connects to the linac in clinical mode and displays, records
and compares real-time machine parameters to the planned parameters. A new
quantity called integral error keeps a running total of leaf overshoot and
undershoots errors in each leaf pair multiplied by leaf width and the amount of
time during which error exists in MU delivery. Another tool reconstructs pinnacle
format delivered plan based on the saved machine logfile and recalculates actual
delivered dose in patient anatomy. Delivery characteristics of various standard
and hypofractionation VMAT plans delivered on Elekta Axesse and Synergy linacs
were quantified. RESULTS: The MLC and gantry errors for all the treatment sites
were 0.00+/-0.59mm and 0.05+/-0.31 degrees , indicating a good MLC gain
calibration. Standard fractionation plans had a larger gantry error than
hypofractionation plans due to frequent dose rate changes. On average the MLC
errors were negligible but larger errors of 4-6 mm and 2.5 degrees were seen
when dose rate varied frequently. Large gantry errors occurred during the
acceleration and deceleration process, and correlated well with MLC errors
(p<0.0001). PTV mean, minimum, maximum dose discrepancy were 0.87+/-0.21%, 0.99+/
0.59% and 1.18+/-0.52%. The other OAR doses were within 2.5% except a few that
showed up to 5.6% discrepancy in maximum dose. Realtime displayed normalized
total positive integral error (normalized to the total MUs) correlated linearly
with MLC and gantry errors (p<0.001) and dosimetric discrepancy (PTVmean: p<0.01;
PTVmax: p<0.067 and PTVmax: p<0.046). CONCLUSIONS: Errors may exist during
complex VMAT planning and delivery. LDM is capable of detecting and quantifying
mechanical and dosimetric errors at various stages of planning and delivery.
PMID- 28518269
TI - MO-F-213AB-05: Commissioning of Gated RapidArc Radiotherapy for Treatment of
Moving Targets.
AB - PURPOSE: To commission and evaluate gated RapidArc radiotherapy of a linear
accelerator (Varian TrueBeam) for treatment of moving targets using a
programmable dynamic phantom. METHODS: The phantom used had different dosimetry
inserts for measurement of dose and dose distribution. It could be programmed to
move in the anterior-posterior and superior-inferior axes with different motion
patterns, amplitudes and frequencies to simulate lung motions of patients. A set
of 4D CT images was acquired with the aid of a Varian RPM system. Images acquired
at the 40, 50 and 60% of the motion cycle were selected and transferred to a
treatment planning system (Varian Eclipse) for planning. A two-arc RapidArc
treatment plan was generated for a C-shaped target volume with a conformity index
of 1.49 and transferred to the TrueBeam for treatment delivery. Dose and dose
distribution measurements were performed using a 0.057 cc ionization chamber and
radiochromic films, respectively and compared with the TPS calculations. Five
treatment fractions were given in three days with two different target motion
patterns to assess the consistency of the dose delivery. RESULTS: Agreement
between TPS calculation and measurement were within 1.64% for dose and 3% or 3mm
in distance to agreement for dose distribution. Repeatability of dose delivery
between treatments was within 0.1% (1SD) in the five treatment fractions
delivered in three days. The time required to deliver a dose of 2 Gy to a moving
C-shaped target using gated RapidArc technique with two gantry rotations was
about 15 minutes. CONCLUSIONS: The geometric and dosimetric accuracy and
consistency of gated RapidArc radiotherapy had been verified. Our study indicated
that the accuracy and consistency of the treatment modality were acceptable for
clinical implementation.
PMID- 28518271
TI - MO-E-BRCD-01: Proton Treatment Planning Issues.
AB - : Proton treatment planning involves many issues that affect the accuracy and
robustness of treatment planning and delivery. Some issues such as patient setup
uncertainty and CT number calibration are common with photon planning but have
potentially greater effects on the treatment plan simulation and delivery for
proton. Other issues such as range uncertainty and LET and RBE variations are
unique to particle therapy. The complications of proton treatment planning have
been well documented in the literature but there are multiple planning methods
developed by clinics to reduce or avoid proton dosimetry errors in treatment
delivery. Additionally, error reduction methods are dependent upon the delivery
Method: scattering or scanning, single-field optimization or multi-field
optimization. This educational session will discuss the documented proton
treatment planning issues and the methods developed in three different clinical
centers to minimize or eliminate the errors associated with the issues for
various treatment sites and proton treatment modalities. LEARNING OBJECTIVES: 1.
Understand the issues associated with proton treatment planning and the effects
of range uncertainty, LET variations, and setup uncertainties. 2. Understand the
differences of photon and proton treatment planning issues. 3. Understand the
methods developed to reduce errors in proton treatment planning and delivery at
three different centers.
PMID- 28518272
TI - MO-F-BRB-01: Extracting Material Information from the CT Numbers by Artificial
Neural Network for Use in the Monte Carlo Simulations of Tissues in
Brachytherapy.
AB - PURPOSE: The Artificial Neural Networks (ANNs) are useful in solving nonlinear
processes, without the need to mathematical models of the parameters. Since the
relationship between the CT numbers and material compositions is not linear, we
can use the AANs for tissue density calibration. The aim of this study is to
obtain the composition and mass density of different tissues which are necessary
in Monte Carlo simulation of different tissues in brachytherapy treatment
planning using ANNs. METHODS: The ANNs were used for mass density calibration.
First, the density and composition of several tissues of the body, along with
their corresponding CT numbers are used as the training samples. After the
network is trained, it would give us the material information, i.e. mass density,
and material composition corresponding to each CT numbers. The tissue
compositions and densities predicted by the ANN for each CT number, were compared
with the real values of such parameters. The tissue parameters predicted by the
ANN were used as the phantom materials for obtaining the dose at different
distances from Pd-103, and Cs-137 brachytherapy sources. Finally the dose at
different distances of the real phantoms were compared with dose around the
phantoms predicted by ANN. RESULTS: The ANN used in this study, can predict the
material compositions of different tissues precisely. For example, it can give
the mass densities of bone, water, and muscle with the percentage differences of
0.62%, - 1.1%, and 0.33% respectively. Comparing the dose distribution inside the
water phantom predicted by Artificial Neural Networks and the real water phantom,
shows the percentage difference of less than 0.7% and 2% for Cs-137 and Pd-103
respectively. CONCLUSIONS: The ANNs are applicable in determination of tissue
parameters from the CT images data, and the material compositions and density
obtained by this methods can be used for material definition in Monte Carlo
simulations.
PMID- 28518273
TI - MO-D-213AB-01: A Brief History of Medical Physics Reimbursement.
AB - : "Corporate memory" is important in many areas of medical physics, but
especially so in the area of economics. To appreciate where medical physics
currently resides in the reimbursement arena, it is imperative that we know from
whence we came. This talk will trace the history of medical physics
reimbursement, chiefly in the area of radiation oncology since most of our
reimbursement codes appear in that clinical specialty. We will begin with the
initiation of the Harvard RBRVS system and the effect it had on our field.
Subsequently, we will trace the impact of new technological advances in the field
and how, at each juncture, the reimbursement associated with these advances
directly impacted our employment opportunities and salaries. Although much of the
operations of the three chief panels associated with health care reimbursement,
the Current Procedural Terminology (CPT) Editorial Panel, the Relative-Value
Update Committee (RUC) and the Centers for Medicare and Medicaid Services (CMS)
are confidential in nature, the history of how these panels operate and their
impact on how health care is reimbursed is important to our field. For those of
us who have labored in this arena over the years, there are successes and
failures as new procedures in radiation oncology were taken for reimbursement
consideration, initially by the Joint Economics Committee of ACR and ASTRO, and
later by ASTRO in collaboration with AAPM. These will be discussed in a general
sense to avoid confidentiality breaches. As we progressed from the use of CT
planning images with 3D conventional therapy, brachytherapy -high and low dose
rate systems, IMRT planning and delivery (with concomitant plan verification
work) to the latest procedures of SRS and SBRT with Image Guided Radiation
Therapy (IGRT), each procedure has its own story surrounding how its
reimbursement was developed. Where no confidentiality issues are involved, the
stories behind the scenes will be discussed as these procedures were taken
forward in the reimbursement process. Going forward, changes in how we are
reimbursed for our services will inevitably occur. For our imaging colleagues,
their work will still be classed as a cost center for their departments. AAPM PEC
is evaluating how they can begin being reimbursed with explicit CPT codes, but
this will take some effort. LEARNING OBJECTIVES: 1. Understand where medical
physics reimbursement came from in radiation oncology 2. Understand the
arrangement of our societies and interaction with reimbursement entities 3.
Understand how medical physics workforce and remuneration for services is
structured 4. Understand what the future may bring in medical physics
reimbursement.
PMID- 28518270
TI - MO-F-BRA-02: Evaluation of 4D CT to 4D Cone-Beam CT Deformable Image Registration
for Lung Cancer Adaptive Radiation Therapy.
AB - PURPOSE: To evaluate two deformable image registration (DIR) algorithms for the
purpose of contour mapping to support image guided adaptive radiotherapy (IGART)
with 4D cone beam CT (4DCBCT). METHODS: Eleven locally advanced non-small cell
lung cancer (NSCLC) patients underwent one planning 4D fan- beam CT (4DFBCT) and
seven weekly 4DCBCT scans. Gross tumor volume (GTV) and carina were delineated by
a physician in all 4D images. For day to day registration, the end of inspiration
4DFBCT phase was deformably registered to the corresponding phase in each 4DCBCT
image. For phase to phase registration, the end of inspiration phase from each 4D
image was registered to end of expiration phase. The delineated contours were
warped using the resulting transforms and compared to the manual contours through
Dice similarity coefficient (DSC), false positive and false negative indices,
and, for carina, target registration error (TRE). Two DIR algorithms were tested:
1) small deformation, inverse consistent linear elastic (SICLE) algorithm and 2)
Insight Toolkit diffeomorphic demons (DEMONS). RESULTS: For day to day
registrations, the mean DSC was 0.59 +/- 0.16 after rigid registration, 0.72 +/-
0.13 with SICLE and to 0.66 +/- 0.18 with DEMONS. SICLE and DEMONS reduced TRE to
4.1 +/- 2.1 mm and 5.8 +/- 3.7 mm respectively, from 6.2 +/- 3.5 mm; and reduced
false positive index to 0.27 and 0.26 respectively from 0.46. Registration with
the cone beam as the fixed image resulted in higher DSC than with the fan beam as
fixed (p < 0.001). SICLE and DEMONS increased the DSC on average by 10.0% and
8.0% and reduced TRE by 2.8 mm and 2.9 mm respectively for phase to phase DIR.
CONCLUSIONS: DIR achieved more congruent mapping of target structures to
delineations than rigid registration alone, although DIR performance varied with
algorithm and patient. This work was supported by National Cancer Institute Grant
No. P01 CA 116602.
PMID- 28518275
TI - MO-F-213AB-02: Correcting Spread-Out Bragg Peak Slope Using Time-Resolved Monte
Carlo Simulations and Beam Current Modulation.
AB - PURPOSE: To fully characterize the spread-out Bragg peak from the Mevion S250
Proton Therapy System using Monte Carlo simulations, evaluate the slope of the
spread-out Bragg peak in the treatment field, and correct this slope by virtually
applying beam current modulation. METHODS: MCNPX simulations were performed on
the Mevion S250 for each of the 24 beamline configurations, with the modulator
wheel rotated in 1 degree increments. Energy deposition was tallied in a water
phantom, resulting in 8,640 central axis depth-dose calculations. These data were
imported into MATLAB and the slope of the spread-out Bragg peak (SOBP) was
evaluated for a constant beam current. An iterative algorithm was developed to
determine the optimal beam current modulation (BCM) profile as a function of
modulator wheel position for each configuration. These BCM profiles were then
applied virtually to the MCNPX SOBP data and slope values were recalculated for
the optimized SOBP profiles. RESULTS: Ideally SOBP slope would measure 0.0 %/cm
in the treatment field, corresponding to a uniform dose delivery. Prior to BCM
correction, slopes between -1.0 and +2.0 %/cm were observed across all beamline
configurations. These were reduced to +/-0.2 %/cm by applying optimized BCM
profiles. The algorithm converged quickly, validating its underlying assumption
that the optimal SOBP profile can be determined by considering only a single dose
values at the depths of maximum individual Bragg peak dose. CONCLUSIONS:
Optimized BCM profiles adequately reduce SOBP slope in the treatment field, and
may be further studied using time-resolved MCNPX simulations. The algorithm
presented efficiently calculates BCM profiles, fully accounting for beamline
scatter and partial-shining effects across adjacent steps on the range modulator
wheels, and without requiring direct measurements. Future work includes applying
this same algorithm to optimize the SOBP distal dose profile. Partially supported
by MEVION Medical Systems, Inc.
PMID- 28518274
TI - MO-D-BRB-10: Modeling Inter-Patient Variation of Organ-At-Risk Sparing in IMRT
Plans: An Evidence-Based Plan Quality Evaluation.
AB - PURPOSE: To develop a predictive model to assess the quality of critical organ
dose sparing in IMRT plans by providing patient specific dose sparing references,
based on an array of patient anatomical features and prior planning experience.
METHODS: Contributions of various patient anatomical features to the inter
patient OAR dose sparing variation in IMRT planning were systematically studied
using machine learning method based on high quality prior plans. The dependence
of anatomical factor on OAR dosimetric parameters is formulated into predictive
models. The OAR dosimetric parameters generated by these predictive models
represent the "best feasible" clinical outcomes based on past planning
experiences. IMRT plans of 88 prostate, 106 head-and-neck (HN) and 21 spine SBRT
treatments were used to train the models. The final models were tested by
additional 24 prostate and 48 HN plans. The model for spine SBRT was tested by
the leave-one-out method. RESULTS: For HN and prostate planning, the significant
patient anatomical features that affect OAR sparing are: the distance between OAR
and PTV, the portion of OAR volume within an OAR specific distance range, the
overlap volume between OAR and PTV, and the portion of OAR volume outside the
primary treatment field. For spine SBRT planning, the most significant patient
anatomical feature that affects cord sparing is the tightness of the geometric
enclosure of PTV surrounding the cord and the homogeneity of PTV dose coverage.
The dosimetric parameters predicted for the test patient cases using the models
were in agreement with those from the clinical plans in more than 75% of the
cases. CONCLUSIONS: The developed predictive models indicated substantial
correlation between some important patient anatomical features and OAR dose
sparing based on expert experiences. These models can be used as effective tools
for evaluating the quality of treatment plans customized to individual patient's
anatomy. Partially supported by a master research agreement with Varian Medical
System, Inc.
PMID- 28518277
TI - MO-F-BRB-05: Monte Carlo Modeling of the Novalis TX Stereotactic Radiosurgery
Mode.
AB - PURPOSE: To model the stereotactic mode of the Varian-Brainlab Novalis TX linear
accelerator using the BEAMnrc Monte Carlo user code Methods: The EGSnrc Monte
Carlo user codes BEAMnrc and DOSXYZnrc were used for photon simulations and dose
calculations, respectively. A Monte Carlo model of a Varian Clinac 21 EX was
modified to model the stereotactic radiosurgery (SRS) mode of the Novalis, taking
into account the smaller dimensions of the SRS flattening filter and limited
field sizes. The parameters of source such as energy, size and angular spread,
were readjusted following a new procedure outlined by Almberg et al, 2012. A
component module, DYNVMLC, previously used to model the Varian Millennium 120
multi-leaf collimator (MLC), was reprogrammed to include the four leaf types of
the Varian high definition 120 leaf MLC. Interleaf air-gap and leaf density were
adjusted to match interleaf leakage profiles measured with EBT2 film. Subsequent
validation included profiles, percent depth dose curves and output factors
measured with ion chambers, and other film measurements. RESULTS: From PDD
measurements, the energy of the incident electron beam was determined to be 6.6
MeV. From penumbra measurements, the electron radial intensity distribution,
given as the full width at half maximum of a Gaussian distribution, was found to
be 0.7 mm (cross-plane) and 0.8 mm (in-plane). From profiles in water, the mean
angular spread had to be adjusted to 1.27 degrees to achieve an acceptable
match. The interleaf air-gap and the density of the leaves of the HDMLC were
determined to be 0.0047 cm and 18.5 g/cm3 , respectively. CONCLUSIONS: The
Almberg procedure was successfully implemented in determining the electron beam
parameters to model the Novalis Tx's SRS mode. Dose profiles simulated with the
new HDMLC component module agreed with measurements within 2%.
PMID- 28518276
TI - MO-B-211-01: Linac-Based IMRT/VMAT Commissioning and QA Program Development.
AB - : Intensity modulated radiotherapy (IMRT) has been used clinically for many
years. Reports from the RPC indicate that up to 30% of the institutions fail to
pass RPC IMRT credentialing process on the first attempt. While volumetric
modulated arc therapy (VMAT) has been introduced more recently, it has quickly
gained wide clinical use. In spite of the long history with IMRT and rapid
adoption of VMAT, commissioning and developing a quality assurance (QA) program
continues to be a challenge especially in busy departments. These points indicate
that a review of commissioning and quality assurance for IMRT is still very much
needed. In this session, the development of an overall IMRT/VMAT QA program, the
role of team members and on-going program functions will be described including
aspects of both quality and safety. General issues and specifics of IMRT/VMAT
commissioning and quality assurance will be covered. While the general principles
of commissioning and QA apply to any device capable of intensity-modulation,
specific examples will be provided for Elekta and Varian linear accelerators.
Strategies for commission and useful checklists will be discussed as well as some
differences between Elekta and Varian technologies. There will also be a focus on
practical advice towards the implementation and on-going QA of linac-based IMRT
and VMAT. Patient- specific QA strategies along with the comparison of different
QA equipment and techniques will be presented. Lastly, differences will be
highlighted between IMRT and VMAT for patient-specific QA. LEARNING OBJECTIVES:
1. Understand approaches to IMRT/VMAT commissioning and QA 2. Describe most
relevant issues in patient-specific QA for IMRT/VMAT 3. Discuss issues with IMRT
/VMAT QA equipment and techniques.
PMID- 28518278
TI - MO-D-BRB-03: Comparison of Proton Therapy Institutional Data Collected by the
RPC.
AB - PURPOSE: To detail and compare data collected during RPC onsite dosimetry review
visits at proton therapy centers. METHODS: The RPC has established a complete
review process for proton therapy institutions wishing to participate in NCI
funded clinical trials that includes an on-site dosimetry review visit performed
by the RPC. During the visit, the RPC takes measurements that include CT# vs.
relative stopping power (RSP) conversion, beam output, depth dose, lateral
profiles, QA procedure reviews and anthropomorphic phantom irradiations. The RPC
reviewed beam output, depth dose and lateral profiles for 5 specific anatomic
treatment sites, reference, prostate, lung, brain, and spine as compared to the
institution's measured or treatment planning-derived values. In addition, the RPC
has compared results from each institution's proton prostate phantom irradiation.
RESULTS: All of the institutions visited had RPC/Institution output ratios that
ranged between 0.95 - 1.02 where the acceptance criterion was +/-5%. For the CT#
to RSP comparison, there was a larger variability. Only two institutions agreed
within five percent of the recommended values, while the other five institutions
had disagreements of up to 20 percent in the high density (high CT number) region
of the conversion curve that may have a clinical impact on dose delivery. For the
prostate phantom irradiation, 3 institutions failed to meet the RPC's +/-7%/4mm
acceptance criteria on the initial attempt, but in the end all 7 sites met the
criteria. CONCLUSIONS: The proton beam output for 7 proton centers, as measured
by the RPC, is comparable (+/-5%), however, there are large discrepancies in the
CT# vs RSP conversion curves used from institution to institution. As a result of
the RPC onsite dosimetry review visits, several institutions have modified their
procedures and dosimetry parameters to improve proton therapy delivery for NCI
funded clinical trials. Work supported by grants CA10953, CA059267, and CA81647
(NCI, DHHS).
PMID- 28518279
TI - MO-D-213CD-02: Non-Contrast-Enhanced Magnetic Resonance Angiography Methods for
Assessment of Morphology and Flow.
AB - : Traditional clinical MR Angiography (MRA) provides volumetric datasets to
characterize the vessel lumen. These MRA techniques can be generally separated
into two categories: * contrast-enhanced MRA, which requires the venous injection
of a paramagnetic contrast agent in form of a Gadolinium chelate and * non
contrast-enhanced MRA (NCE MRA), which relies on signal properties of the blood
or the motion of the blood to create signal differences between the blood pool
and the surrounding tissues. Time-of-Flight (TOF) and Phase- Contrast (PC)
imaging have been developed as NCE techniques in the early days of MR imaging.
However, widespread clinical adaptation of MRA did not occur until the
introduction of CE-MRA in the mid-1990ies with significantly improved robustness.
Recent developments have renewed the interest in imaging approaches that do not
rely on any external contrast agents. Advances in hardware, especially gradient
amplifiers and multi-channel coil technology, have reduced imaging times,
improved the signal-to-noise ratio, and reduced artefacts so that NCE MRA is
becoming competitive again. These approaches provide viable alternatives in
patients that are at risk for nephrogenic systemic fibrosis (NSF) and should not
receive a Gd-based contrast agent. In addition, some of those approaches provide
insights in functional information beyond the standard luminography. For example,
arterial spin labeling (ASL) imaging can be used as a 'pseudo arterial injection'
by labeling blood in targeted volumes and tracking its distribution over time.
Novel '4D MR Flow' imaging is an extension of traditional PC MRA to capture
volumetric velocity vector fields throughout the cardiac cycle, thereby allowing
for direct measures of hemdodynamic parameters such as pressure gradient, wall
shear stress, pulse wave velocity, kinetic energy, and more. This lecture will
provide an overview of the underlying contrast mechanisms of time-of-flight,
phase-contrast, balanced steady state free precession (bSSFP), and ASL MRA.
Current and potential future roles of these approaches in clinical imaging will
also be discussed. LEARNING OBJECTIVES: 1. Understand the various origins of MRA
contrast mechanisms that do not require a contrast agent. 2. Understand the
issues related to NCE-MRA imaging including design, acquisition and processing.
3. Understand the benefits, pitfalls, and future potentials of these approaches.
My research is sponsored by GE Healthcare.
PMID- 28518280
TI - MO-C-BRCD-03: The Role of Informatics in Medical Physics and Vice Versa.
AB - : Like Medical Physics, Imaging Informatics encompasses concepts touching every
aspect of the imaging chain from image creation, acquisition, management and
archival, to image processing, analysis, display and interpretation. The two
disciplines are in fact quite complementary, with similar goals to improve the
quality of care provided to patients using an evidence-based approach, to assure
safety in the clinical and research environments, to facilitate efficiency in the
workplace, and to accelerate knowledge discovery. Use-cases describing several
areas of informatics activity will be given to illustrate current limitations
that would benefit from medical physicist participation, and conversely areas in
which informaticists may contribute to the solution. Topics to be discussed
include radiation dose monitoring, process management and quality control,
display technologies, business analytics techniques, and quantitative imaging.
Quantitative imaging is increasingly becoming an essential part of
biomedicalresearch as well as being incorporated into clinical diagnostic
activities. Referring clinicians are asking for more objective information to be
gleaned from the imaging tests that they order so that they may make the best
clinical management decisions for their patients. Medical Physicists may be
called upon to identify existing issues as well as develop, validate and
implement new approaches and technologies to help move the field further toward
quantitative imaging methods for the future. Biomedical imaging informatics tools
and techniques such as standards, integration, data mining, cloud computing and
new systems architectures, ontologies and lexicons, data visualization and
navigation tools, and business analytics applications can be used to overcome
some of the existing limitations. LEARNING OBJECTIVES: 1. Describe what is meant
by Medical Imaging Informatics and understand why the medical physicist should
care. 2. Identify existing limitations in information technologies with respect
to Medical Physics, and conversely see how Informatics may assist the medical
physicist in filling some of the current gaps in their activities. 3. Understand
general informatics concepts and areas of investigation including imaging and
workflow standards, systems integration, computing architectures, ontologies,
data mining and business analytics, data visualization and human-computer
interface tools, and the importance of quantitative imaging for the future of
Medical Physics and Imaging Informatics. 4. Become familiar with on-going efforts
to address current challenges facing future research into and clinical
implementation of quantitative imaging applications.
PMID- 28518281
TI - MO-D-BRB-07: Failure-Mode and Effects Analysis Study for CyberKnife Stereotactic
Radiosurgery.
AB - PURPOSE: The purpose of this study is to conduct a Failure Modes and Effect
Analysis (FMEA) for CyberKnife Stereotactic Radiosurgery to determine the
sensitivity of existing QA procedures and determine in which areas new QA
procedures needed to be implemented. METHODS: Members from each professional team
providing service for CyberKnife radiosurgery (Medical Physicists, Nurses,
Physicians, Radiation Therapists, and Administrators) were interviewed to gather
potential failure modes. A patient flow chart was developed from patient consult
to conclusion of last treatment. Failure modes were mapped to nodes in the flow
charts to identify potential high-risk areas. A matrix was created to correlate
existing QA procedures with failure modes to identify failure modes that were not
covered by any QA as well as identify the sensitivity of QA procedures to prevent
failures. RESULTS: 180 failure modes were identified. Current AAPM QA
recommendations were found to focus preferentially on technical failure modes
(15%), while the majority of failure modes found are process failures and human
errors (85%). Creating a Venn diagram of CyberKnife and Gamma Knife failure modes
revealed a large overlap area. The most effective QA checks are checklists for
physics second chart review and pre- treatment time-out checklists. Existing
checklists were modified and new checklists added to address high-ranked failure
modes. New procedure guidelines, e.g. for contouring workflow and add-on
simulations, were developed as QC to address clusters of failure modes. An ARIA
CyberKnife DICOM interface is being implemented to resolve failure modes
centering around multiple fraction, multiple plan treatments and total dose
tracking. CONCLUSIONS: This work is the first FMEA study for the CyberKnife
stereotactic radiosurgery. It will facilitate medical physicists using the
CyberKnife to deliver SRS/SBRT treatments to transition from experience-based
technical QA to a comprehensive new quality paradigm including technical,
process, and human safety aspects.
PMID- 28518282
TI - MO-D-218-01: Overview of Methodology and Standards (QIBA, IEC, AIUM and AAPM).
AB - : Ultrasound system standards and professional guidelines can facilitate
efficient provision of medical physics services and growth of ultrasound imaging
if the documents are well designed and are utilized. We too often develop our own
phantoms and procedures and never converge to obtain a critical mass of data on
system performance and value of such services. Standards can also produce
unnecessary costs and limit innovation if not carefully developed, reviewed, and
changed as needed. There are quite a few new initiatives that, if followed
vigorously, could improve medical ultrasound and medical physicists'
contributions thereto. This talk is to explain many of the existing standards and
recommendations for ultrasound system quality control, performance evaluation,
and safety, as well as current and suggested efforts in these areas. The primary
standards body for medical ultrasound systems is now the International
Electrotechnical Commission (IEC). Uniformity across the world is helpful to all
if the documents are reasonably current. There still is a role for traditional
bodies such as the AAPM with its valuable report series and the American Inst. of
Ultras. in Med. (AIUM) with its own standards and reports and its joint work with
the Medical Imaging Technology Alliance (MITA). All three, with strong
involvement of FDA scientists and with some efforts from the Acoustical Society
of America have historically provided the main standards affecting medical
physicists. Now that the lengthy IEC process is moving more smoothly, our
national bodies still can provide new developments and drafts that can be offered
as needed for international standardization. The ACR in particular can provide
meaningful incentives through ultrasound service accreditation. Without any
regulatory or strong consumer push, reports and standards on ultrasound system
performance have received only modest use in the USA. A consistent consumer or
accreditation push might be justified now. A series of three standards on
performance evaluation is well on its way to covering pulse echo ultrasound well,
with IEC 61319-1 on spatial measurements, IEC 61319-2 on depth of penetration and
local dynamic range and one draft and one Technical Specification 62558 on small
void imaging. A new effort has just been initiated to help drive more and better
use of quantitative ultrasound imaging in human and surrogate studies and in
clinical use. A shear wave speed ultrasound technical committee will carry out
this effort in the Quantitative Imaging Biomarkers Alliance (QIBA) that is
managed by the RSNA. LEARNING OBJECTIVES: 1. Understand the coverage of the two
current and third planned IEC medical ultrasound performance evaluation standards
that could form a basis for stable performance evaluation tests. 2. Understand
the coverage of the Current AIUM and ACR QC documents and the drafting and
support efforts in the IEC. 3. Understand the need for and partial availability
of simplified software and instructions to improve and facilitate performance of
these tests? 4. Understand how standards development can lead to improved
understanding and performance of medical ultrasound imaging as is anticipated for
the new QIBA effort.
PMID- 28518284
TI - Molecular profiling as a novel tool to predict response to interferon-alpha2 in
MPNs: The proof of concept in early myelofibrosis.
PMID- 28518283
TI - Branched-chain amino acids for people with hepatic encephalopathy.
AB - BACKGROUND: Hepatic encephalopathy is a brain dysfunction with neurological and
psychiatric changes associated with liver insufficiency or portal-systemic
shunting. The severity ranges from minor symptoms to coma. A Cochrane systematic
review including 11 randomised clinical trials on branched-chain amino acids
(BCAA) versus control interventions has evaluated if BCAA may benefit people with
hepatic encephalopathy. OBJECTIVES: To evaluate the beneficial and harmful
effects of BCAA versus any control intervention for people with hepatic
encephalopathy. SEARCH METHODS: We identified trials through manual and
electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials
Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE,
Embase, Science Citation Index Expanded and Conference Proceedings Citation Index
- Science, and LILACS (May 2017). SELECTION CRITERIA: We included randomised
clinical trials, irrespective of the bias control, language, or publication
status. DATA COLLECTION AND ANALYSIS: The authors independently extracted data
based on published reports and collected data from the primary investigators. We
changed our primary outcomes in this update of the review to include mortality
(all cause), hepatic encephalopathy (number of people without improved
manifestations of hepatic encephalopathy), and adverse events. The analyses
included random-effects and fixed-effect meta-analyses. We performed subgroup,
sensitivity, regression, and trial sequential analyses to evaluate sources of
heterogeneity (including intervention, and participant and trial
characteristics), bias (using The Cochrane Hepato-Biliary Group method), small
study effects, and the robustness of the results after adjusting for sparse data
and multiplicity. We graded the quality of the evidence using the GRADE approach.
MAIN RESULTS: We found 16 randomised clinical trials including 827 participants
with hepatic encephalopathy classed as overt (12 trials) or minimal (four
trials). Eight trials assessed oral BCAA supplements and seven trials assessed
intravenous BCAA. The control groups received placebo/no intervention (two
trials), diets (10 trials), lactulose (two trials), or neomycin (two trials). In
15 trials, all participants had cirrhosis. We classed seven trials as low risk of
bias and nine trials as high risk of bias (mainly due to lack of blinding or for
profit funding). In a random-effects meta-analysis of mortality, we found no
difference between BCAA and controls (risk ratio (RR) 0.88, 95% confidence
interval (CI) 0.69 to 1.11; 760 participants; 15 trials; moderate quality of
evidence). We found no evidence of small-study effects. Sensitivity analyses of
trials with a low risk of bias found no beneficial or detrimental effect of BCAA
on mortality. Trial sequential analysis showed that the required information size
was not reached, suggesting that additional evidence was needed. BCAA had a
beneficial effect on hepatic encephalopathy (RR 0.73, 95% CI 0.61 to 0.88; 827
participants; 16 trials; high quality of evidence). We found no small-study
effects and confirmed the beneficial effect of BCAA in a sensitivity analysis
that only included trials with a low risk of bias (RR 0.71, 95% CI 0.52 to 0.96).
The trial sequential analysis showed that firm evidence was reached. In a fixed
effect meta-analysis, we found that BCAA increased the risk of nausea and
vomiting (RR 5.56; 2.93 to 10.55; moderate quality of evidence). We found no
beneficial or detrimental effects of BCAA on nausea or vomiting in a random
effects meta-analysis or on quality of life or nutritional parameters. We did not
identify predictors of the intervention effect in the subgroup, sensitivity, or
meta-regression analyses. In sensitivity analyses that excluded trials with a
lactulose or neomycin control, BCAA had a beneficial effect on hepatic
encephalopathy (RR 0.76, 95% CI 0.63 to 0.92). Additional sensitivity analyses
found no difference between BCAA and lactulose or neomycin (RR 0.66, 95% CI 0.34
to 1.30). AUTHORS' CONCLUSIONS: In this updated review, we included five
additional trials. The analyses showed that BCAA had a beneficial effect on
hepatic encephalopathy. We found no effect on mortality, quality of life, or
nutritional parameters, but we need additional trials to evaluate these outcomes.
Likewise, we need additional randomised clinical trials to determine the effect
of BCAA compared with interventions such as non-absorbable disaccharides,
rifaximin, or other antibiotics.
PMID- 28518405
TI - Setting Ambitious yet Achievable Targets Using Probabilistic Projections: Meeting
Demand for Family Planning.
AB - In 2015, governments adopted 17 internationally agreed goals to ensure progress
and well-being in the economic, social, and environmental dimensions of
sustainable development. These new goals present a challenge for countries to set
empirical targets that are ambitious yet achievable and that can account for
different starting points and rates of progress. We used probabilistic
projections of family planning indicators, based on a global data set and
Bayesian hierarchical modeling, to generate illustrative targets at the country
level. Targets were defined as the percentage of demand for family planning
satisfied with modern contraceptive methods where a country has at least a 10
percent chance of reaching the target by 2030. National targets for 2030 ranged
from below 50 percent of demand satisfied with modern contraceptives (for three
countries in Africa) to above 90 percent (for 41 countries from all major areas
of the world). The probabilistic approach also identified countries for which a
global fixed target value of 75 percent demand satisfied was either unambitious
or has little chance of achievement. We present the web-based Family Planning
Estimation Tool (FPET) enabling national decision makers to compute and assess
targets for meeting family planning demand.
PMID- 28518345
TI - Severe neonatal alloimmune thrombocytopenia caused by maternal sensitization
against a new low-frequency alloantigen (Domb ) located on platelet glycoprotein
IIIa.
PMID- 28518406
TI - Host density increases parasite recruitment but decreases host risk in a snail
trematode system.
AB - Most species aggregate in local patches. High host density in patches increases
contact rate between hosts and parasites, increasing parasite transmission
success. At the same time, for environmentally transmitted parasites, high host
density can decrease infection risk to individual hosts, because infective stages
are divided among all hosts in a patch, leading to safety in numbers. We tested
these predictions using the California horn snail, Cerithideopsis californica
(=Cerithidea californica), which is the first intermediate host for at least 19
digenean trematode species in California estuaries. Snails become infected by
ingesting trematode eggs or through penetration by free-swimming miracidia that
hatch from trematode eggs deposited with final-host (bird or mammal) feces. This
complex life cycle decouples infective-stage production from transmission,
raising the possibility of an inverse relationship between host density and
infection risk at local scales. In a field survey, higher snail density was
associated with increased trematode (infected snail) density, but decreased
trematode prevalence, consistent with either safety in numbers, parasitic
castration, or both. To determine the extent to which safety in numbers drove the
negative snail-density-trematode-prevalence association, we manipulated
uninfected snail density in 83 cages at eight sites within Carpinteria Salt Marsh
(California, USA). At each site, we quantified snail density and used data on
final-host (bird and raccoon) distributions to control for between-site variation
in infective-stage supply. After three months, overall trematode infections per
cage increased with snail biomass density. For egg-transmitted trematodes, per
snail infection risk decreased with snail biomass density in the cage and
surrounding area, whereas per-snail infection risk did not decrease for
miracidium-transmitted trematodes. Furthermore, both trematode recruitment and
infection risk increased with infective-stage input, but this was significant
only for miracidium-transmitted species. A model parameterized with our
experimental results and snail densities from 524 field transects estimated that
safety in numbers, when combined with patchy host density, halved per capita
infection risk in this snail population. We conclude that, depending on
transmission mode, host density can enhance parasite recruitment and reduce per
capita infection risk.
PMID- 28518407
TI - NAD+ : A big player in cardiac and skeletal muscle remodeling and aging.
AB - In the past decade, NAD+ has gained importance for its beneficial effects as
antioxidant and anti-aging molecule. A paper in science by Zhang et al. () has
described that NAD+ when replenished, ameliorates muscle dystrophy in mice by
improving mitochondrial function. NAD+ was also demonstrated by the authors to
improve the life span of mice. Cox et al. () demonstrated the cardiac effects of
NAD+ which mitigated chronic heart failure via mitochondrial redox state
mechanism. Cox et al. () also demonstrated that NAD+ is provided in the drinking
water, it improves cardiac relaxation in volume overload model of heart failure.
Although NAD+ has a profound anti-aging and anti-oxidant effects, its effect on
humans and use as a dietary supplement needs more exploration.
PMID- 28518408
TI - S-Adenosylmethionine-mediated apoptosis is potentiated by autophagy inhibition
induced by chloroquine in human breast cancer cells.
AB - The naturally occurring sulfonium compound S-adenosyl-L-methionine (AdoMet) is an
ubiquitous sulfur-nucleoside that represents the main methyl donor in numerous
methylation reactions. In recent years, it has been shown that AdoMet possesses
antiproliferative properties in various cancer cells, but the molecular
mechanisms at the basis of the effect induced by AdoMet have been only in part
investigated. In the present study, we found that AdoMet strongly inhibited the
proliferation of breast cancer cells MCF-7 by inducing both autophagy and
apoptosis. AdoMet consistently enhanced the levels of the autophagy markers
beclin-1 and LC3B-II, and caused a significant increase of pro-apoptotic Bax/Bcl
2 ratio paralleled by poly (ADP ribose) polymerase (PARP) and caspase 9, and 6
cleavage. Notably, AdoMet, already at low doses, raised the percentage of cells
in G2 /M phase of cell cycle by down-regulating the expression of cell cycle
regulatory proteins cyclin B and cyclin E with a remarkable increase of p53, p27,
and p21. We also evaluated the combination of AdoMet and the autophagy inhibitor
chloroquine (CLC) showing that autophagy block is synergistic in inducing both
growth inhibition and apoptosis. These effects were paralleled by a strong
inhibition of the activity of AKT and of the downstream effector mTOR and by an
increased cleavage of caspase-6 and PARP. These data suggest, for the first time,
that autophagy can act as an escape mechanism from the apoptotic activity of
AdoMet, and that AdoMet could be used in combination with CLC or its analogs in
the treatment of breast cancer.
PMID- 28518409
TI - Metabolic nodal response as a prognostic marker after neoadjuvant therapy for
oesophageal cancer.
PMID- 28518411
TI - Multicentre observational study of adherence to Sepsis Six guidelines in
emergency general surgery.
PMID- 28518410
TI - Meta-analysis of adjuvant therapy following curative surgery for periampullary
adenocarcinoma.
AB - BACKGROUND: Periampullary cancers are uncommon malignancies, often amenable to
surgery. Several studies have suggested a role for adjuvant chemotherapy and
chemoradiotherapy in improving survival of patients with periampullary cancers,
with variable results. The aim of this meta-analysis was to determine the
survival benefit of adjuvant therapy for periampullary cancers. METHODS: A
systematic review was undertaken of literature published between 1 January 2000
and 31 December 2015 to elicit and analyse the pooled overall survival associated
with the use of either adjuvant chemotherapy or chemoradiotherapy versus
observation in the treatment of surgically resected periampullary cancer.
Included articles were also screened for information regarding stage, prognostic
factors and toxicity-related events. RESULTS: A total of 704 titles were
screened, of which 93 full-text articles were retrieved. Fourteen full-text
articles were included in the study, six of which were RCTs. A total of 1671
patients (904 in the control group and 767 who received adjuvant therapy) were
included. The median 5-year overall survival rate was 37.5 per cent in the
control group, compared with 40.0 per cent in the adjuvant group (hazard ratio
1.08, 95 per cent c.i. 0.91 to 1.28; P = 0.067). In 32.2 per cent of patients who
had adjuvant therapy, one or more WHO grade 3 or 4 toxicity-related events were
noted. Advanced T category was associated worse survival (regression coefficient
0.14, P = 0.040), whereas nodal status and grade of differentiation were not.
CONCLUSION: This systematic review found no associated survival benefit for
adjuvant chemotherapy or chemoradiotherapy in the treatment of periampullary
cancer.
PMID- 28518413
TI - Spanish translation section.
PMID- 28518414
TI - Systematic review of surgical and medical treatment for tertiary
hyperparathyroidism.
AB - BACKGROUND: A significant proportion of patients with chronic kidney disease and
secondary hyperparathyroidism (HPT) remain hyperparathyroid after kidney
transplantation, a state known as tertiary HPT. Without treatment, tertiary HPT
can lead to diminished kidney allograft and patient survival. Parathyroidectomy
was commonly performed to treat tertiary HPT until the introduction of the
calcimimetic drug, cinacalcet. It is not known whether surgery or medical
treatment is superior for tertiary HPT. METHODS: A systematic review was
performed and medical literature databases were searched for studies on the
treatment of tertiary HPT that were published after the approval of cinacalcet.
RESULTS: A total of 1669 articles were identified, of which 47 were included in
the review. Following subtotal and total parathyroidectomy, initial cure rates
were 98.7 and 100 per cent respectively, but in 7.6 and 4 per cent of patients
tertiary HPT recurred. After treatment with cinacalcet, 80.8 per cent of the
patients achieved normocalcaemia. Owing to side-effects, 6.4 per cent of patients
discontinued cinacalcet treatment. The literature regarding graft function and
survival is limited; however, renal graft survival after surgical treatment
appears comparable to that obtained with cinacalcet therapy. CONCLUSION: Side
effects and complications of both treatment modalities were mild and occurred in
a minority of patients. Surgical treatment for tertiary HPT has higher cure rates
than medical therapy.
PMID- 28518415
TI - Systematic review of transarterial embolization for hepatocellular adenomas.
AB - BACKGROUND: Hepatocellular adenoma (HCA) larger than 5 cm in diameter is
considered an indication for elective surgery, because of the risk of haemorrhage
and malignant transformation. Transarterial embolization (TAE) is used to manage
bleeding HCA and occasionally to reduce tumour size. TAE might have potential as
an elective therapy, but its current role in this context is uncertain. This
systematic review provides an overview of clinical outcomes after TAE, in
bleeding and non-bleeding HCA. METHODS: Two independent reviewers performed a
systematic search of literature in PubMed and Embase. Outcomes were change in
tumour size, avoidance of surgery, complications and malignant transformation
after TAE in bleeding and non-bleeding HCA. The Critical Appraisal Skills
Programme tool for cohort studies was used for quality assessment of included
studies. RESULTS: From 320 potential articles, 20 cohort studies and 20 case
reports including 851 patients met the inclusion criteria. TAE was performed in
151 of 851 patients (17.7 per cent), involving 196 tumours, of which 95 (48.5 per
cent) were non-bleeding. Surgical treatment was avoided in 68 of 151 patients
(45.0 per cent). Elective TAE was performed in 49 patients involving 66 HCAs,
with 41 of these patients (84 per cent) not requiring surgery. Major
complications occurred in eight of 151 patients (5.3 per cent); no death was
reported. Among cohort studies, complete tumour disappearance was observed in 10
per cent of patients, and regression in 75 per cent. CONCLUSION: Acute or
elective TAE in the management of HCA is safe. In the elective setting, TAE
provides a potential alternative to surgery.
PMID- 28518475
TI - Lipid bodies accumulation in Leishmania infantum-infected C57BL/6 macrophages.
AB - Lipid bodies (LBs) are intracellular accumulations of neutral lipids surrounded
by a single membrane. These organelles are involved in the production of
eicosanoids, which modulate immunity by either promoting or dampening
inflammatory responses. Leishmania infantum, the etiological agent of visceral
leishmaniasis in Brazil, is an intracellular parasite that causes disease by
suppressing macrophage microbicidal responses. C57BL/6 mouse bone marrow-derived
macrophages infected with L. infantum strain LcJ had higher numbers of LB+ cells
(P<.0001) and total LBs than noninfected cultures. Large (>3 MUm) LBs were
present inside parasitophorous vacuoles (PVs). These results contrast with those
of L. infantum-infected BALB/c macrophages, in which the only LBs are derived
from parasite, not macrophage origin. Increased LBs in C57BL/6 macrophages in
close association with parasites would position host LBs where they could
modulate L. infantum infection. These results imply a potential influence of the
host genetics on the role of LBs in host-pathogen interactions. Overall, our data
support a model in which the expression, and the role of LBs upon infection,
ultimately depends on the specific combination of host-pathogen interactions.
PMID- 28518476
TI - Adult-onset, chronic, cyclic thrombocytopenia in a Rhesus macaque (Macaca
mulatta) after dengue virus vaccination and viral challenge.
AB - An 8-year-old, male Rhesus macaque (Macaca mulatta), previously used for dengue
virus (DENV) vaccine research with viral challenge, was presented with adult
onset, chronic, cyclic thrombocytopenia. Platelet number, morphology, and
function were evaluated by automated hematology, peripheral blood smears,
electron microscopy, flow cytometry, and impedance aggregometry. Bone marrow was
evaluated by cytology. Both serum anti-dengue nonstructural protein 1 (NS1)
antibodies and anti-platelet antibodies were detected by ELISA. Platelet
characterization showed a lack of aggregation to all agonists (ADP, ASP, and
collagen), increased activation with increased expression of surface marker (HLA
ABC), and an absence of surface receptor GPIX during clinical episodes of
petechiae and ecchymoses, even in the presence of normal platelet counts. Bone
marrow aspirates identified potential mild megakaryocytic hypoplasia. All
platelet functions and morphologic attributes were within normal limits during
clinically normal phases. Presence of anti-dengue NS1 serum antibodies confirmed
a positive DENV titer 8 years postvaccination. Based on the history and clinical
findings, a primary differential diagnosis for this chronic, cyclic platelet
pathology was autoimmune platelet destruction with potential bone marrow
involvement.
PMID- 28518479
TI - SU-E-T-500: Pencil-Beam versus Monte Carlo Based Dose Calculation for Proton
Therapy Patients with Complex Geometries. Clinical Use of the TOPAS Monte Carlo
System.
AB - PURPOSE: To investigate the necessity of the verification of dose distributions
using Monte Carlo (MC) simulations for proton therapy of head and neck patients
and other complex patient geometries. METHODS: TOPAS, a TOol for PArticle
Simulations that makes MC simulations easy-to-use for research and clinical use
and is layered on top of Geant4, has been used to simulate the treatments of head
and neck patients at the Massachusetts General Hospital (MGH). The resulting dose
distributions have been compared to pencil beam calculations based on the XiO
treatment planning system. Dose difference distributions were used to highlight
areas where the two algorithms did not agree. Dose volume histograms are utilized
to investigate the overall agreement of the planned doses in target structures.
RESULTS: 21 head and neck patients, both nasopharynx and spinal cord, were
investigated. The field complexity ranges from a single field up to 13 fields.
For all patients, the dose in the clinical target volume agrees well.
Nevertheless, differences in critical structures around the targets have been
observed mostly due to range differences between the two algorithms. CONCLUSIONS:
Pencil beam algorithms provide an accurate description of dose in the target
volume. However, we conclude that the differences between MC simulations and
pencil beam algorithms in regions outside the target for complex geometries, such
as present in head and neck patients, support the necessity of routine use of MC
simulations for treatment verifications before treatment. TOPAS is aiming to make
such routine simulations available to all researchers and clinics. An automated
interface utilizing TOPAS to enable such simulations has been developed at MGH
and should become routinely used in the near future for patients with complex
geometries. NIH/NCI R01 CA140735.
PMID- 28518478
TI - Robotic lower anterior resection for a regrowth following complete clinical
response - a video vignette.
PMID- 28518481
TI - SU-E-T-532: Comparison of Dose Distributions Calculated Using Different Planning
Systems with Radiochromic Film Measurements in an Inhomogeneous Phantom.
AB - PURPOSE: Accurate modeling of the dose distribution in a lung tumor is
challenging for traditional dose calculation algorithms. We compare the dose
distributions of four commercial dose calculation Methods: Raysearch (Raysearch
Laboratories) and Pinnacle (Philips Healthcare) collapsed cone, and Eclipse AAA
and Eclipse Acuros,(Varian Medical Systems) with measurements using radiochromic
film in a lung tumor phantomMethods: A simple lung tumor phantom was constructed
using a thermoplastic cylinder 29 mm diameter and 40mm in length (density 1.3
gm/cc) imbedded in cork phantom 25 * 25 * 20 cm of density 0.32 gm/cc. Nine film
layers normal to the axis of the cylinder where placed between layers of cork,
above, below and through the cylindrical inhomogeneity. The phantom was
irradiated with a single asymmetric 10*10 cm 6 MV field with the central axis
collinear with the cylinder axis. Thirteen film exposures at 5 cm depth taken
with doses 0-10 Gy were used to calibrate the film. The phantom was CT scanned
and the DICOM study loaded into each of the treatment planning systems to
calculate the dose distribution in the phantom. RESULTS: Away from cork-poly
interfaces, agreement between the four algorithms was within 3% of the film
measurements. For Acuros, the dose at the edge of the cylinder was found to be up
to 2% lower than that at the center of the cylinder possibly because of the loss
of lateral electron equilibrium. CONCLUSIONS: All four algorithms achieved
remarkable agreement with the radiochromic film measurement. The Acuros algorithm
appeared to more accurately model the peripheral dose deficit in the tumor,
although a more detailed study is required for confirmation.
PMID- 28518480
TI - SU-E-T-521: Dosimetric Effect on Variation of Patient Size in Prostate Volumetric
Modulated Arc Therapy.
AB - PURPOSE: To evaluate dosimetric variations of planning target volume (PTV) on
critical organs such as rectal wall, bladder and femoral head, when the patient
size changes due to weight loss in prostate volumetric modulated arc therapy
(VMAT). METHODS: Three patients with small (32.0 cm3 ), medium (48.4 cm3 ) and
large (86.5 cm3 ) prostate, selected from a group of 30 were planned for prostate
VMAT using the 6 MV photon beam. Patient size reduction due to weight loss was
modeled by contracting the external body contour with reduced depths (0.5 - 2 cm)
in the anterior and both lateral directions. Original normal tissue excluded from
the contracted body contour was replaced by air. Dose calculation was repeated
with the same planned beam geometry and dose prescription. Dose-volume
histograms, dose-volume points of the PTV, clinical target volume (CTV) and
critical organs were calculated with variations of reduced depth. RESULTS: D99%
of the PTV and CTV were found to have increased 2.65 +/- 0.03% per cm and 2.75 +/
0.15% per cm of reduced depth in the range of 0.5 and 2 cm. D30% of the rectal
wall and bladder increased 2.29 +/- 0.12% per cm and 2.31 +/- 0.83% per cm,
respectively. D5% of the femoral head increased by 3.30 +/- 0.11% per cm of
reduced depth. Moreover, there was more than 5% increase of minimum, maximum and
means doses for the PTV, CTV and critical organs when the reduced depth reached 2
cm. CONCLUSIONS: This study provided estimated results of dosimetric changes due
to variation of patient size in prostate VMAT. The dosimetric information should
help radiation oncology staff to justify changes of dose distribution, when
patient weight loss occurs during prostate VMAT. Dose variations of more than 5%
were found when the patient's reduced depth was equal to 2 cm. Actual or
potential conflicts of interest do not exist.
PMID- 28518482
TI - SU-E-T-543: Beam Attenuation Characteristics of Treatment Couches.
AB - PURPOSE: Measure photon beam attenuation characteristics of the Varian EXACT,
Varian IGRT treatment couches and two CIVCO Universal extensions; and assess
accuracy of Varian's Eclipse treatment planning system in modeling the beam
attenuation of each couch. METHODS: Dose Measurements were taken using a Farmer
ion chamber inside a cylindrical acrylic phantom. They were taken for two photon
energies (6MV and 15MV), at three different field sizes, for various gantry
angles through the couch. EXACT couch was tested both with the adjustable rails
pushed to the outside of the couch, and pushed to the center of the couch. IGRT
couch was divided by thickness into three sections. Effects on surface dose were
measured using a Tissue Maximum Ratio or Percent Depth Dose curve. CIVCO
extensions were CT scanned for inclusion in the planning system. All measurements
were modeled in the Eclipse treatment planning system for comparison. RESULTS:
Maximum attenuation was measured at 6MV with the smallest field for all couch
setups. The EXACT couch produced a maximum attenuation of 19.2% and a surface
dose increase of 47% of Dmax through the couch. Maximum attenuation for the IGRT
couch and both CIVCO extensions were between 6-8%. Through the couch, the IGRT
couch showed a surface dose increase of 29% of Dmax,; the CIVCO extensions
produced a surface dose increase of 33% and 7% of Dmax. Maximum difference
between measured and planned dose was 7%, for the EXACT couch, 1.9% for the IGRT
couch and 2.4% for both CIVCO extensions. CONCLUSIONS: These treatment couches
were shown to affect delivered and surface dose. Including the couch structure
during treatment planning can account for the couch attenuation in most cases,
but some attenuation values are underestimated in the planning software. Largest
effects are for oblique treatment angles using low energy and small field sizes.
PMID- 28518483
TI - SU-E-T-514: Implementation and Commissioning of a Micro Multileaf Collimator in
Pinnacle Treatment Planning System.
AB - PURPOSE: To model and validate, in a Pinnacle treatment planning system, a
Brainlab micromultileaf collimator mounted on a Primus Siemens accelerator. The
objective is to take advantage of the collapsed cone convolution algorithm and
the ability of this system modelling rounded leaf- end MLC's. METHOD: The micro
multileaf collimator was modelled using fixed accelerator jaws with a value of
9.2*9.2 cm2 . Profiles and depth dose curves for a wide range of square fields at
SSD of 100 cm and depths of 1.5,5,10 and 20 cm were measured using a Scanditronix
stereotactic SFD diode. Output factors were measured using a stereotactic
unshielded diode for field sizes from 0.6*0.6 cm2 to 3*3 cm2 . For wider fields a
Scanditronix ic15 ionization chamber was used. EDR2 films were used to measure
adjacent fields in the transverse and longitudinal direction. The film
measurements were compared to Pinnacle calculations to model and validate the
leaf tip radius, leaf offset calibration values and tongue and groove width.
RESULTS: Pinnacle calculations and measurements agree within 2% or 2mm except for
the tails of largest fields where differences are <3.5%. Comparison of film
measurements and Pinnacle calculations give the optimal value for leaf tip radius
of 15 cm and for tongue and groove width of 0.04 cm. CONCLUSIONS: Pinnacle models
a Brainlab micromultileaf collimator mounted on a Siemens Primus accelerator with
acceptable results for clinical treatments.
PMID- 28518477
TI - Acute oligodendrocyte loss with persistent white matter injury in a third
trimester equivalent mouse model of fetal alcohol spectrum disorder.
AB - Alcohol exposure during central nervous system (CNS) development can lead to
fetal alcohol spectrum disorder (FASD). Human imaging studies have revealed
significant white matter (WM) abnormalities linked to cognitive impairment in
children with FASD; however, the underlying mechanisms remain unknown. Here, we
evaluated both the acute and long-term impacts of alcohol exposure on
oligodendrocyte number and WM integrity in a third trimester-equivalent mouse
model of FASD, in which mouse pups were exposed to alcohol during the first 2
weeks of postnatal development. Our results demonstrate a 58% decrease in the
number of mature oligodendrocytes (OLs) and a 75% decrease in the number of
proliferating oligodendrocyte progenitor cells (OPCs) within the corpus callosum
of alcohol-exposed mice at postnatal day 16 (P16). Interestingly, neither mature
OLs nor OPCs derived from the postnatal subventricular zone (SVZ) were
numerically affected by alcohol exposure, indicating heterogeneity in
susceptibility based on OL ontogenetic origin. Although mature OL and
proliferating OPC numbers recovered by postnatal day 50 (P50), abnormalities in
myelin protein expression and microstructure within the corpus callosum of
alcohol-exposed subjects persisted, as assessed by western immunoblotting of
myelin basic protein (MBP; decreased expression) and MRI diffusion tensor imaging
(DTI; decreased fractional anisotropy). These results indicate that third
trimester-equivalent alcohol exposure leads to an acute, albeit recoverable,
decrease in OL lineage cell numbers, accompanied by enduring WM injury.
Additionally, our finding of heterogeneity in alcohol susceptibility based on the
developmental origin of OLs may have therapeutic implications in FASD and other
disorders of WM development.
PMID- 28518484
TI - SU-E-T-554: PTV to Skin Proximity for Head and Neck IMRT Treatment Planning.
AB - PURPOSE: The goal of this work was to evaluate measured vs. calculated surface
dose as a function of PTV-to-skin proximity and calculation matrix oxel size,
determine effects on plan quality, and provide parameters and levels of
uncertainty for clinical use. METHODS: A right-sided CTV with the lateral border
5mm from the surface was delineated on the CT data of a head and neck phantom. A
5mm PTV was generated except laterally where distances of 0-5mm were used. A 7
field IMRT plan was generated using the Eclipse TPS. Optimization was performed
where 95% of the PTV receives the prescription dose using a matrix size of 2mm3 .
Dose calculations were repeated for grid sizes of 1, 3 and 5mm3 . For each plan
nine point dose values were obtained just inside the phantom surface,
corresponding to a 2cm2 grid near the central target region. Nine ultra-thin TLDs
were placed on the phantom surface corresponding to the grid. Measured and
calculated dose values were compared. Conformality, homogeneity and target
coverage were compared. RESULTS: Surface dose is over-estimated by the TPS by 21
and 8% for 5 and 3mm3 voxels, respectively and accurately predicted for 2mm3
voxels. A voxel size of 1mm3 results in underestimation of 13%. Conformality
improves with increasing PTV to skin distance and a CI of unity results for grid
sizes of 1-3mm3 between 4 and 4.5mm. Hot spot decreases as the PTV moves away
from the surface and falls below 110% at 4mm. Underdosage worsens as the PTV
approaches the skin. CONCLUSIONS: For decreasing PTV-to-skin distance with this
TPS, isodose conformality decreases, 'hot spot' increases, and target coverage
degrades. Surface dose is accurately predicted for a 2mm3 voxel size, while
choosing a finer or coarser grid results in underestimation or overestimation,
respectively. All of the above appear to hold for VMAT.
PMID- 28518485
TI - SU-E-T-525: Dosimetric Validation of the Algorithm Based on Linear Boltzmann
Transport Equations for Photon 4MV Dose Calculation.
AB - PURPOSE: To evaluate a dosimetric accuracy of AcurosXB dose calculation algorithm
for 4 MV photon beam. METHODS: Four MV beam (Clinac-6EX) and AAA and AcurosXB
algorithms (pre-release version 11.0.03.) were used in this study. The
differences of the calculation with AAA (EAAA) and AcurosXB (EAXB) to the
measurement were evaluated in the depth doses to 25 cm depth and dose profiles
within the water and slab phantoms (water, lung and bone equivalent). In
addition, the clinical cases, including three whole breast plans and three head
and neck IMRT plans, were evaluated. First the AAA plans were calculated, then
AcurosXB plans were recalculated with dose-to-medium with identical beam setup
and monitor units as in the AAA plan. RESULTS: In the water phantom study, the
EAAA and EAXB were up to 2.2% and 1.5% in the depth doses for the open field
(field size = 4 - 40cm square), respectively. Under the heterogeneity conditions,
the EAAA and EAXB were less than 4.4% and 2.2% in lung region, and less than
12.5% and 6.3% in bone region, respectively. In the re-buildup region after
passing through the lung phantom, the AAA overestimated the doses about 10%;
however AcurosXB had good agreement with measurement within 3%. Dose profiles
with AcurosXB were better agreement with measurement than AAA. In the clinical
cases, the dose of the skin surface region with AcurosXB were higher than AAA by
at least 10%, and the dose differences over 5% appeared in heterogeneous region.
However, DVH shapes of each organ were similar between AAA and AcurosXB within
2%. CONCLUSIONS: In phantom study, AcurosXB had better agreement to measurement
than AAA, especially in heterogeneous region and re-buildup region. In the
clinical cases, there were large differences between AcurosXB and AAA in the
surface region. Evaluation Agreement of non-clinical versions of Acuros XB
witha??Varian Medical Systems.
PMID- 28518486
TI - SU-E-T-536: Is BJR Supplement #25 Recommendation for Megavoltage Energy
Independent Scatter Factor Still Valid for Flattening Filter Free Photon Beams?
AB - PURPOSE: In the process of measuring and validating fundamental dosimetry data
prior to the clinical use of a treatment unit, it is prudent to compare
measurements with previously published equivalent data. During the commissioning
of an accelerator with flattening filter free (FFF) photon beams (Varian True
Beam 6 MV FFF and 10 MV FFF) we compared measured Phantom Scatter Factors (Sp)
with the Normalized Peak Scatter Factors (NPSFs) from the British Journal of
Radiology Supplement 25 (BJR #25). The purpose of this work was to determine
whether the energy independent NPSFs BJR#25 are valid for comparison with FFF
photon beams. METHODS: All measurements were performed using a Varian TrueBeam
linear accelerator with photon energies of 6-MV, 6-MV FFF and 10-MV FFF modes.
For all measurements, a Scanditronix CC04 ionization chamber was used. Both water
and in-air measurements were made to obtain NPSFs normalized to the 10 * 10 cm2
field size. For measurements in water, the chamber was positioned at 100 cm
source-to-axis distance at the depth of dose maximum. For in-air measurements,
the chamber was positioned at 100 cm source-to-axis distance with appropriate
build-up cap. From BJR #25, NPSFs were obtained for comparison with the
measurements. RESULTS: The NPSF agreement between the 6-MV and 6-MV FFF with the
BJR#25 were all within +/-0.5%. The agreement ranged from 0.996 to 1.004 and
0.995 to 1.002 for 6-MV and 6-MV FFF, respectively. We also found that 10-MV FFF
showed very similar trend. CONCLUSIONS: The scatter factors reported in BJR #25
are valid for comparison for 6-MV, 6-MV FFF, and 10-MV. Additional investigation
is needed to further understand the dosimetric characteristics of FFF mode.
PMID- 28518487
TI - SU-E-T-502: Dose Perturbation Effects Near Implant Surfaces Caused by Secondary
Electron Transport in Photon-Beam Therapy.
AB - PURPOSE: To investigate the dose perturbation effects at interfaces between water
and a Titanium implant, attributable to secondary electron transport across the
interface, during high energy photon radiotherapy. While dose enhancement is
characteristic for the proximal interface of a high-atomic number implant, the
dose perturbation at the distal interface varies from reduction to enhancement,
requiring proper computation of secondary electron transport effects. The
backward and forward perturbation factors pb and pf will be calculated. METHODS:
Using DOSRZnrc, depth dose curves were computed in a water phantom using photon
spectra of nominal energies 4, 6, 10, 15, 24 MV for conditions (i) homogeneous
water without any insert, (ii) alternatively with Titanium inserts of thicknesses
3 and 5 cm placed at 10 cm water depth. Backscatter factor pb was computed as the
ratio of the dose with implant against that without implant, whereas pf was
calculated by first accounting for photon attenuation in the implant and then
taking the ratio of the dose with implant against that without implant. RESULTS:
At the front interface, pb is independent of the material thickness and varies
slightly with beam energy and incident angle. On consideration of photon
attenuation in the implant, pf was also found to be independent on material
thickness, but strongly varying with energy, including change of sign.
CONCLUSIONS: For 4-24 MV photon beams the maximum spread of the dose perturbation
effect remains within only a few millimeters from the interface, with pb values
ranging from 1.18-1.22, while factor pf ranges from 0.9-1.21 at normal incidence,
indicating the extent to which planning systems may over- or underestimate the
doses near implant interfaces. At inclined beam incidence the dose perturbation
effects even increase, and for instance pb (1.24-1.25) and pf (0.85-1.32) were
determined for 6 MV and 24 MV beams at 45 degrees incidence.
PMID- 28518488
TI - SU-E-T-547: Rotating Shield Brachytherapy (RSBT) for Cervical Cancer.
AB - PURPOSE: To assess rotating shield brachytherapy (RSBT) delivered with the
electronic brachytherapy (eBT) source comparing to intracavitary (IC) and
intracavitary plus supplemental interstitial brachytherapy (IC+IS BT) delivered
with conventional isotope radiation source. METHOD AND MATERIALS: IC, IC+IS and
RSBT plan was simulated for 5 patients with advanced cervical cancer (>40cc). One
BT plan for each patient (fraction 1) guided by magnetic resonance imaging (MRI)
was used in our treatment planning system (TPS). A bio- and MRI-compatible
polycarbonate (Makrolon Rx3158) intrauterine applicator was simulated for IC and
RSBT, and the vienna applicator was simulated for IC+IS BT. 192Ir was used as the
radiation source of IC and IC+IS BT; Xoft AxxentTM eBT source was used for RSBT.
A 0.5 mm thick tungsten shield was used for RS-BT with different azimuthal and
zenith angles. The total dose for each plan was escalated as the external beam
radiation therapy (EBRT) plus BT times fraction number (5 in our case). RESULTS:
RSBT and IC+IS BT had higher dose conformity in terms of D90 than IC BT for all
the patients. The advantage of RSBT over IC+IS BT was dependent on the shield
emission angle, tumor shape and tandem applicator location. The delivery time of
RSBT was increased as finer emission angle was selected. CONCLUSIONS: RSBT is a
less-invasive potential alternative to conventional IC and IC+IS BT for treating
bulky (>40cc) cervical cancer. RSBT can provide better treatment outcome with
clinically acceptable increased delivery time if proper emission angle is
selected based on the tumor shape and tandem applicator location. supported in
part by NSF grants CCF-0830402 and CCF-0844765; and the NIH grant K25-CA123112,
and American Cancer Society seed grant (IRG-77-004-31).
PMID- 28518489
TI - SU-E-T-518: Dose Perturbation at Air-Tissue Interface in Proton Beam Therapy.
AB - PURPOSE: The loss of transverse equilibrium along the central axis of the proton
beam in the presence of the air/tissue interface creates dose perturbation that
has not been fully quantified. This gets magnified in small fields that are used
for lung and patch up fields. Air-tissue dose perturbation is studied in a
phantom and verified with Monte Carlo simulation. METHODS: Air channel of
variable thickness that could be found in trachea, larynx and small lesions in
lung were studied. To mimic air/tissue interface a simple phantom geometry was
used with EBT films. The results confirmed the presence of dose perturbations
which were investigating using water phantom in reference condition (10*10 cm2
field, 16 cm range and 10 cm SOBP). A variable air column was created in the
front of the phantom. A small volume ion chamber was used to collect high
resolution profile data in water. The simulation was performed with 3*107
particles with the Monte Carlo particle transport code FLUKA version 2011.2.10
with cut off energy of 100keV. RESULTS: The dose perturbations were visible on
film and quantified by ion chamber measurements in water. Dose perturbations at
air-tissue interfaces are shown to be significant (-20 to +30%). The measured
profiles show significant discontinuities in dose up to +30% in low density
medium. The magnitude is dependence on the location and width of the air gap.
Under and over dose perturbation pattern is not predicted by treatment planning
system (TPS) due to proton transport algorithm and calculation bin. The Monte
Carlo simulation confirmed our measured data. CONCLUSIONS: Significant dose
perturbation exists with high-dose region in low density medium that is not
predicated by TPS. The magnitude and shape is position and gap size dependent.
This study provides the presence of dosimetric discontinuities that should be
evaluated clinically at interfaces.
PMID- 28518490
TI - SU-E-T-558: Assessing the Effect of Inter-Fractional Motion in Esophageal Sparing
Plans.
AB - PURPOSE: To compare esophageal dose distributions in esophageal sparing IMRT
plans with predicted dose distributions which include the effect of inter
fraction motion. METHODS: Seven lung cancer patients were used, each with a
standard and an esophageal sparing plan (74Gy, 2Gy fractions). The average max
dose to esophagus was 8351cGy and 7758cGy for the standard and sparing plans,
respectively. The average length of esophagus for which the total circumference
was treated above 60Gy (LETT60) was 9.4cm in the standard plans and 5.8cm in the
sparing plans. In order to simulate inter-fractional motion, a three-dimensional
rigid shift was applied to the calculated dose field. A simulated course of
treatment consisted of a single systematic shift applied throughout the treatment
as well a random shift for each of the 37 fractions. Both systematic and random
shifts were generated from Gaussian distributions of 3mm and 5mm standard
deviation. Each treatment course was simulated 1000 times to obtain an expected
distribution of the delivered dose. RESULTS: Simulated treatment dose received by
the esophagus was less than dose seen in the treatment plan. The average
reduction in maximum esophageal dose for the standard plans was 234cGy and 386cGY
for the 3mm and 5mm Gaussian distributions, respectively. The average reduction
in LETT60 was 0.6cm and 1.7cm, for the 3mm and 5mm distributions respectively.
For the esophageal sparing plans, the average reduction in maximum esophageal
dose was 94cGy and 202cGy for 3mm and 5mm Gaussian distributions, respectively.
The average change in LETT60 for the esophageal sparing plans was smaller, at
0.1cm (increase) and 0.6cm (reduction), for the 3mm and 5mm distributions,
respectively. CONCLUSIONS: Interfraction motion consistently reduced the maximum
doses to the esophagus for both standard and esophageal sparing plans.
PMID- 28518491
TI - SU-E-T-529: Dosimetric Evaluation with Heterogeneity in Acuros XB Advanced Dose
Calculation Algorithm and Anisotropic Analytical Algorithm (AAA).
AB - PURPOSE: To evaluate accuracy of Acuros XB Advanced Dose Calculation Algorithm
and Anisotropic Analytical Algorithm (AAA) with measurements in predicting doses
beyond air gaps. METHODS AND MATERIALS: Three virtual phantoms with layers were
created in Eclipse Treatment Planning System. Each layer in phantoms was assigned
in terms of water (top), air (middle) and water (bottom) medium. Central axis
depth dose in water (bottom medium) beyond 2, 4 and 6 cm air gaps were computed
for 5 cm water equivalent material positioned before air gaps. Dose computation
was performed for 6MV photon beam with 3*3 and 5*5 cm2 field sizes at 100 cm SSD
to surface of phantoms using AAA_10.0.28 and Acuros XB_10.0.28. Next, solid water
and Styrofoam were manufactured to mimic virtual phantoms. By keeping identical
field, beam parameters, and geometries that were used for dose computation, 100
MUs were delivered to phantoms, and measurements at selected depths were acquired
with cylindrical ionization chamber. Measured central axis depth doses were
compared against calculated central axis depth doses computed from Acuros XB and
AAA. RESULTS: Acuros XB predicted doses within +/-2% of measured doses except at
1cm depth in phantoms with 4 cm air gap (-2.4%) and 6 cm air gap (-2.8%) for
field size 3*3cm2 . Acuros XB showed better dose prediction compared to AAA at
all measured depths. Smallest test field size in phantom with largest air gap
produced highest range (between depths 1 and 5 cm) in percentage dose difference
(AAA: -2.9% to -9.9% and Acuros XB: -2.8% to 1.5%). Improper modeling of primary
beam attenuation or lateral scatter (or combination of both) within air gap may
have resulted into dose discrepancies. CONCLUSIONS: The findings suggest Acuros
XB is more accurate to use in dose predictions when tumor is located beyond small
air cavity (heterogeneity) within the patient.
PMID- 28518492
TI - SU-E-T-540: Evaluation of Forced-Density Corrected Dose Calculation for Lung
Cancer Treatment.
AB - PURPOSE: The study was aimed to evaluate the accuracy of lung cancer treatment
dose calculations using a bulk electron density for forced-density correction, in
situations where CT images are acquired in other institutions and the information
of CT number to electron density (CT-to-ED) conversion is unavailable for
conducting pixel density correction. METHODS: Eleven 3D SBRT lung cases were
studied. Treatment plans were generated initially with pixel-density correction
using a known CT-to-ED conversion, in a CMS XIO treatment planning system using
superposition algorithm. The plans were re-calculated with contour-based density
correction, i.e., forced-density correction: a density of 0.26 g/cm3 was assigned
to lung structures, which was a population average taken from a literature, and
unit density was assigned to other structures. Monitor units were kept the same
in both plans. RESULTS: The doses calculated using forced-density correction were
compared against those calculated using pixel-density correction. The absolute
percentage differences of PTV D95, PTV mean dose, and V20, among the 11 cases,
were 2.49+/-1.69%, 1.69+/-1.5%, and 1.88+/-2.36%, respectively. CONCLUSIONS: The
results showed that the dose calculation using the bulk density and forced
density correction generated dose distributions close to those calculated using
pixel-density correction and actual CT-to-ED conversion. None.
PMID- 28518493
TI - SU-E-T-506: Dosimetric Study for Shallow-Seated Tumor Using Passive/active
Scanning Proton Beam.
AB - PURPOSE: To investigate the possibility of using a single spot scanning proton
beam to treat superficial lesions. METHODS: A cylindrical phantom with a
simulated superficial target (it seated 0.5-4cm depth from the surface, volume:
270cm3 ) was created in Eclipse treatment planning system. Three proton plans
were generated: (a) a single AP uniform scanning beam with aperture and range
compensator; (b) a single AP spot scanning beam with a pre-absorber. The location
and thickness of the pre-absorber were calculated using Geant4 to Monte Carlo
code to make use of the available spot scanning beams to get a conformal plan.
(c) a five-beam spot scanning beam plan using multi-field optimization. The
prescription is 54 cobalt grey equivalent (CGE) which covers 95% of the target.
The target coverage, lateral penumbra at 2 and 4cm depth in water, the doses to
normal tissue (phantom-target) and skin (2mm from the surface) were evaluated and
compared for three plans. RESULTS: The mean doses to the target are comparable
within 2.4% for all three plans. The conformity indices (at 95%) are 1.36, 1.04
and 0.98 for plan (a), (b) and (c) respectively. The lateral penumbra (80% to
20%) for plan (a), (b) are both 0.73 cm, while it is 3.75 cm for plan (c). The
skin dose which received more than 40 (CGE) from plan (a) is 10% higher than that
of other two plans. Plan (c) has 70% higher mean doses to normal tissue than that
of plan (a) and (b). CONCLUSIONS: Each plan provides good coverage of target. And
in this study, it showed that, with a properly designed pre-absorber, it is
possible to use a single spot scanning beam to treat superficial lesion. The plan
provides good target coverage and maintains normal tissue sparing in the mean
time.
PMID- 28518494
TI - SU-E-T-510: Calculation of High Resolution and Material-Specific Photon Energy
Deposition Kernels.
AB - PURPOSE: To calculate photon energy deposition kernels (EDKs) used for
convolution/superposition dose calculation at a higher resolution than the
original Mackie et al. 1988 kernels and to calculate material-specific kernels
that describe how energy is transported and deposited by secondary particles when
the incident photon interacts in a material other than water. METHODS: The high
resolution EDKs for various incident photon energies were generated using the
EGSnrc user-code EDKnrc, which forces incident photons to interact at the center
of a 60 cm radius sphere of water. The simulation geometry is essentially the
same as the original Mackie calculation but with a greater number of scoring
voxels (48 radial, 144 angular bins). For the material-specific EDKs, incident
photons were forced to interact at the center of a 1 mm radius sphere of material
(lung, cortical bone, silver, or titanium) surrounded by a 60 cm radius water
sphere, using the original scoring voxel geometry implemented by Mackie et al.
1988 (24 radial, 48 angular bins). RESULTS: Our Monte Carlo-calculated high
resolution EDKs showed excellent agreement with the Mackie kernels, with our
kernels providing more information about energy deposition close to the
interaction site. Furthermore, our EDKs resulted in smoother dose deposition
functions due to the finer resolution and greater number of simulation histories.
The material-specific EDK results show that the angular distribution of energy
deposition is different for incident photons interacting in different materials.
Calculated from the angular dose distribution for 300 keV incident photons, the
expected polar angle for dose deposition () is 28.6 degrees for water,
33.3 degrees for lung, 36.0 degrees for cortical bone, 44.6 degrees for
titanium, and 58.1 degrees for silver, showing a dependence on the material in
which the primary photon interacts. CONCLUSIONS: These high resolution and
material-specific EDKs have implications for convolution/superposition dose
calculations in heterogeneous patient geometries, especially at material
interfaces.
PMID- 28518495
TI - SU-E-T-531: Verification of Acuros Dose Calculation Accuracy in Lung SBRT.
AB - PURPOSE: The AcurosXB Advanced Dose algorithm (Varian Medical Systems) was
reported to give more accurate dose calculation in heterogeneous medium compared
with the AAA algorithm. In this work, a validation of AcurosXB dose calculation
accuracy is performed for use in lung SBRT. METHODS: A CIRS (Computerized Imaging
Reference Systems, Inc.) lung phantom was used with a tissue equivalent 2cm
circular target inserted into the lung. The phantom was customized to hold a
Gafchromic EBT2 film through the center of the target. The phantom was CT
scanned, and single field (3cm by 3cm anterior/lateral) plans, as well as VMAT
plans were created for 6 and 10 MV energies with different delivery modalities
(with/without a flattening filter). All plans delivered 500 cGy to the PTV which
was the target plus 0.5 cm uniform margin. Plans were delivered on a Varian
TrueBeamTM STx using image guidance to locate the isocenter. The film dose was
compared with Eclipse v10.0 dose calculated with AAA and Acuros algorithms using
FilmQA software (3cognition). Monte Carlo simulations (BEAMnrc/DOSXYZnrc) were
performed to further validate AcurosXB calculations. RESULTS: Within the GTV, AAA
and Acuros algorithms were in good agreement with the film measurements to within
2% mean dose difference. AAA calculation consistently overestimated the dose to
the lung surrounding the GTV by 5-9% for the 10MV beam and 2-4% for the 6MV beam.
Acuros and MC calculations were found to be in good agreement with EBT2 film
measurement within 2% at 6MV including the build up and build down regions.
CONCLUSIONS: The CIRS customized lung phantom with EBT2 films was found to be an
excellent tool in validating the dose calculation algorithm for lung SBRT
application. AcurosXB was found to be more accurate than AAA algorithm in lung
and near lung/tissue interfaces.
PMID- 28518496
TI - SU-E-T-542: Impact of Tongue-And-Groove Width on MLC-Defined Small Field
Dosimetry for Pinnacle 9.0.
AB - PURPOSE: the dosimetric impact of Tongue-and-Groove (TG) width on MLC-defined
small fields of 1cm in X/Y-jaw directions for Pinnacle Version 9.0. METHODS: Open
field of 5cmx5cm was created using the Physics Tool of Pinnacle Version 9.0 and
then the MLC leaves were placed manually for creating MLC-defined small fields of
1cmx2cm to 1cmx5cm as well as of 2cmx1cm to 5cmx1cm at the source-to-surface
distance of 95cm and depth of 5cm. With the commissioned machine data of Varian
6EX, a series of test machines were simulated by changing the size of MLC TG
width (no TG gap, 0.1mm, 0.25mm, 0.5mm, 0.75mm, 1.25mm, and 1.5mm). The other
machine/MLC parameters were set to the commissioned values of Varian 6EX. In
addition, dose grid sizes of 2mm and 4mm were used for dose calculation purpose.
Mapcheck measurements were performed for the MLC-defined fields of 2*1 cm to 5*1
cm to compare with the calculated dose of Pinnacle Version 9.0. RESULTS:
Regardless of MLC-defined small fields with X-direction size of 1cm, there was
negligible variation of calculated dose as TG width varied from zero TG to 1.5mm.
The calculated dose was very sensitive to the dose grid size and there was a good
agreement of less than 3% in between measurement and calculation with the dose
grid size of 2mm. However, there was over 5% discrepancy with the dose grid size
of 4mm for the MLC-defiled small fields. For the MLC-defined small fields with Y
direction size of 1cm, there was over 8% decrease of computed dose compared to
those of small fields with X-direction size of 1 cm, even though the TG width was
set to zero, which was that the effective field size of MLC 5cm*1cm was identical
to that of MLC 1cm*5cm. With the dose grid size of 4mm, the calculated dose was
underestimated over 10% compared to that of 2mm dose grid. CONCLUSIONS: Pinnacle
Version 9.0 was insensitive to the variation of TG width from no TG to 1.5mm for
MLC-defined small fields with X-direction size of 1cm. For the MLC-defined small
fields with Y-direction size of 1cm, there was over 8% decrease of calculated
doses compared to those of small fields with X-direction size of 1 cm, even
though the TG width was set to zero.
PMID- 28518497
TI - SU-E-T-513: Clinical Implementation of a GPU Accelerated Pencil Beam Dose
Calculation Algorithm.
AB - PURPOSE: This work reports a clinical implementation of a GPU accelerated pencil
beam dose calculation algorithm (GPU-PB). METHODS: Model parameters were
determined using in-house scripts written in MATLAB. Dose distributions in a
water phantom were calculated using a Pinnacle TPS for various open field sizes.
Lateral profiles at 2-mm incremental depths were used to calculate PB kernel
parameters. Weighted sum of squares were used for least-squares parameter fitting
utilizing a Levenberg-marquardt algorithm. Weightings were adjusted based on
goodness of fitting and in accordance with field size to suppress deviations due
to horn effects. The scale factor was fitted iteratively. The calculated doses
for two patient cases were analyzed with a 3D gamma method (3%/3mm). RESULTS:
Excellent agreement between Pinnacle calculation and GPU-PB calculation was
achieved regarding PDD, profiles and output factor. For a head-neck 10-field step
and-shoot IMRT case, gamma passing rate was over 99% and maximum absolute dose
value is 75.6 Gy vs. 73.9 Gy, differing by 2.3%. Similar results were obtained
for a SBRT lung case. Gamma passing rate is a function of PB kernel cut-off
distance and beamlet resolution. It appears that if the highest accuracy is
desired, a resolution of 10 mm or better in the direction parallel to MLC travel
and a cutoff distance of 10 cm or better should be used. The calculation time
increases with both cut-off distance and beamlet resolution. For example, GPU
calculation time is 1.36 seconds for 5 cm cut-off distance, and increases to 4.84
s for 15 cm cut-off distance. CONCLUSIONS: A GPU accelerated PB dose calculation
algorithm has been implemented using clinical measurement data. Excellent
agreement with Pinnacle TPS has been achieved. Beamlet size and PB cut-off
distance should be chosen according to desired dose calculation accuracy and
speed.
PMID- 28518498
TI - SU-E-T-553: Dose-Mass Vs. Dose-Volume Optimization: A Phantom Study.
AB - PURPOSE: To demonstrate the merits of mass-based optimization in comparison with
volume-based optimization using a simple test phantom. METHODS: Dose-volume
histogram-based (DVH-based) quadratic objective functions are converted into dose
mass-histogram-based (DMH-based) objective functions by multiplying per-voxel
volumes by per-voxel densities within the objective. A digital phantom with a 1.0
g/cm3 target is constructed for irradiation with two beams: one beam path
contains a 0.2 g/cm3 volume-of-interest (VOI0.2) while the orthogonal beam-path
contains an equal-volume 0.8 g/cm3 VOI (VOI0.8). Monitor-units are computed to
achieve a 100 cGy average target dose for each individual beam, and for two-beam
DVH-based and DMH-based optimizations. RESULTS: For single-beam irradiation
through VOI0.2, the average dose to VOI0.2 is 20.5 cGy. For single-beam
irradiation through VOI0.8, the average dose to VOI0.8 is 25.2 cGy. Traversing
the low density volume results in ~23% lower dose. When DVH- and DMH-based
optimizations are performed such that target dose-volume-histograms of the
optimizations match, for the DVH optimization 60% vs. 40% of the dose is
delivered through VOI0.2 vs. VOI0.8. For DMH-optimization, the split between dose
delivered through VOI0.2 vs. VOI0.8 is 70% vs. 30%. CONCLUSIONS: When density is
constant, there is no difference between DVH- and DMH-based optimizations.
However, in heterogeneous media, DMH and DVH solutions differ when low and high
density materials have the same dose objectives. Delivering target dose through
lower density VOIs facilitates target dose deposition due to a decrease in
attenuating material, and the decreased attenuation lowers dose to the low
density VOI. From mathematical and physical points of view dose-mass optimization
is more general than dose-volume optimization.
PMID- 28518499
TI - SU-E-T-524: The Effect of CT Contrast on CyberKnife Treatment Planning.
AB - PURPOSE: To investigate the effect of CT contrast enhancement (CE) on the 3D dose
distributions of non-coplanar small field beams in the CyberKnife (CK) treatment
planning system. METHODS: Twenty patients treated by pre-CE CT plans were
recruited to this retrospective plan study. Their post-CE CT plans were based on
the pre-CE CT plan data and calculated using the same MU and beam paths in either
Ray-Tracing or Monte Carlo (MC) algorithms. The differences in doses of the beam
path and the reference point and in DVHs of target and OARs between the pre-CE CT
and the post-CE CT plans were compared. The minimum dose, the maximum dose, the
mean dose, and the dose received to 50% of the target and OARs volumes, and the
target volume coverage were also compared. RESULTS: The dose differences between
the pre-CE and post-CE plans in a single beam path were less than 50 cGy in both
calculation algorithms. At the center of target volume, it was 1.9% (maximum
6.2%) in Ray-Tracing and 1.5% (maximum 4.0%) in MC, with respect to the
prescription dose. The post-CE plans showed on average 2% decrease in the OAR
maximum dose (maximum 6.4% in Ray-Tracing and 5.8% in MC). Regardless of the
algorithms, the dose to the target and the target volume coverage of post-CE
plans were on average reduced by 2% and 1 %, respectively, with a maximum
reduction of 6.1% (in Ray-Tracing) in the minimum target dose. CONCLUSIONS: The
CK treatment plan using the post-CE CT could generally result in a few % dose
differences from the pre-CE CT plan. However, it could be more than 6%, depending
on the target positions in the body and the calculation algorithms. Thus the post
CE CT in CK treatment plans should be used with a caution.
PMID- 28518500
TI - SU-E-T-535: Proton Dose Calculations in Homogeneous Media.
AB - PURPOSE: To develop a pencil beam dose calculation algorithm for scanned proton
beams that improves modeling of scatter events. METHODS: Our pencil beam
algorithm (PBA) was developed for calculating dose from monoenergetic, parallel
proton beams in homogeneous media. Fermi-Eyges theory was implemented for pencil
beam transport. Elastic and nonelastic scatter effects were each modeled as a
Gaussian distribution, with root mean square (RMS) widths determined from
theoretical calculations and a nonlinear fit to a Monte Carlo (MC) simulated 1mm
* 1mm proton beam, respectively. The PBA was commissioned using MC simulations in
a flat water phantom. Resulting PBA calculations were compared with results of
other models reported in the literature on the basis of differences between PBA
and MC calculations of 80-20% penumbral widths. Our model was further tested by
comparing PBA and MC results for oblique beams (45 degree incidence) and surface
irregularities (step heights of 1 and 4 cm) for energies of 50-250 MeV and field
sizes of 4cm * 4cm and 10cm * 10cm. Agreement between PBA and MC distributions
was quantified by computing the percentage of points within 2% dose difference or
1mm distance to agreement. RESULTS: Our PBA improved agreement between calculated
and simulated penumbral widths by an order of magnitude compared with previously
reported values. For comparisons of oblique beams and surface irregularities,
agreement between PBA and MC distributions was better than 99%. CONCLUSIONS: Our
algorithm showed improved accuracy over other models reported in the literature
in predicting the overall shape of the lateral profile through the Bragg peak.
This improvement was achieved by incorporating nonelastic scatter events into our
PBA. The increased modeling accuracy of our PBA, incorporated into a treatment
planning system, may improve the reliability of treatment planning calculations
for patient treatments. This research was supported by contract W81XWH-10-1-0005
awarded by The U.S. Army Research Acquisition Activity, 820 Chandler Street, Fort
Detrick, MD 21702-5014. This report does not necessarily reflect the position or
policy of the Government, and no official endorsement should be inferred.
PMID- 28518501
TI - SU-E-T-501: Perturbation of TG-43 Parameters of the Brachytherapy Sources under
Insufficient Scattering Materials.
AB - PURPOSE: According to the TG-43 recommendations of American Association of
Physicist in Medicine (AAPM), the dosimetry parameters of brachytherapy sources
are obtained in a water phantom with full scattering conditions. However, in many
actual clinical treatments the source are not surrounded with sufficient tissue
in all directions to provide the full scattering condition. HDR brachytherapy of
the breast or 125I eye-plaque treatment of the ocular melanoma are among the
treatment sites that fits this category. In this project, the impact of
insufficient phantom material surrounding the 137Cs, 192Ir, and 103Pd
brachytherapy source on their TG43 dosimetric characteristics has been
investigated. METHODS: In this study, the effect of the insufficient tissue
(referred here as missing tissues) around the brachytherapy sources on their TG
43 dosimetric parameters have been investigated using MCNP5 Monte Carlo code. The
brachytherapy sources were simulated in different locations inside a cubical
water phantom with the dimensions of 30*30*30 cm3 . The variation of the
dosimetric parameters of the three sources (i.e. I>, g(r), and F(r,theta)) were
compared to the values from full scattering conditions (i.e. source at the center
of the phantom). RESULTS: The results of this study indicate the variation of
g(r)and 2D anisotropy function of the brachytherapy sources as a function of the
missing tissue thickness. These changes increase by decreasing the energy of the
photons emitted by the brachytherapy sources. These differences are mainly due to
the lack of full scattering condition for the points near the phantom boundary.
CONCLUSIONS: Unlike the published data for symmetric, but insufficient phantom
material around the source, the impact of asymmetric phantom materials have been
evaluated on dosimetric characteristics of the brachytherapy sources.
PMID- 28518502
TI - SU-E-T-546: Cumulative Dose Evaluation for Head and Neck Cancers.
AB - PURPOSE: In this study, we retrospectively analyzed patient treatments utilizing
a prototype of the Varian EclipseTM treatment planning system integrated with
their new DARTTM technology. Structure volume changes, structure displacements,
and dose deviations were analyzed to assess the need for more adaptive treatment
planning. METHODS: Ten patients with head and neck cancer who received daily cone
beam imaging CTs, as part of their radiation therapy, were chosen from the
University of California San Diego Moores Cancer Center database. With the aid of
DARTTM, we were able to retrospectively calculate the accumulated dose to both
the tumor and healthy tissue over the entire course of treatment. This process
was accomplished through rigid and deformable registrations of their daily cone
beam CT scans and cumulative dose measurements. Volumetric changes were compared
to their original planning CT image. RESULTS: Our results showed notable changes
to the parotid glands in all patients, in both structure shrinkage and dose
escalation, which were often correlated with a medial displacement of the glands
towards the high-dose region. Our study estimated that the mean rate of parotid
volume reduction was 0.18 cm3 /treatment day with a range of 0.08 - 0.31 cm3
/treatment day. GTV, CTV, and PTV regions also showed significant volume
reductions which was shown to be more pronounced during the first half of
treatment. In 6 out of 9 patients with contoured parotids, the absorbed dose
increase to these glands was >3%. The GTV, CTV, and PTV showed smaller
variations, and in only 1 out of the 10 patients studied did the dose
accumulation increase >3%. CONCLUSIONS: While the program used was just a
prototype, it is our hope for the future that this project could be integrated
clinically to develop more adaptive treatment plans allowing for better treatment
accuracy and patient care.
PMID- 28518503
TI - SU-E-T-517: Characterization of Relative Doses and Source Strengths for Various
Plaque Sizes and Tumor Dimensions in the Treatment of Uveal Melanoma.
AB - PURPOSE: To characterize the relative doses and source strengths for various eye
plaque sizes and tumor dimensions in the treatment of uveal melanoma. MATERIALS
AND METHOD: Several tumors with basal diameters ranging from 6-16mm and apical
height of 5-10mm were planned using the Pinnacle3 treatment planning system
following the American Brachytherapy Society's recommendations. The data is based
on 5-day implant to deliver 85Gy with a dose rate of 70.9cGy/hr. Choice of plaque
size is based on a 2-3 mm margin on either side of the tumor. Doses to the fixed
locations: sclera, center of the eye and opposite sclera were obtained. RESULTS:
From our results we see larger source strengths needed for smaller plaques due to
smaller number of sources used. The exception is with 14mm and 16mm plaques
containing the same number of sources where the 16mm plaque has slightly higher
source strengths. For both the inner and outer sclera, the relative dose
increases with increasing height. For a 12mm plaque, the relative dose of the
outer sclera increases from 4-10 times that of the Rx dose at the apex of the
tumor. For a 20mm eye plaque, the relative dose of the outer sclera increases
from 2-5 times that of the prescription dose at the apex of the tumor. As apical
height increases, the relative dose at the center of the eye increases to about
75% of the Rx dose at 10cm depth for all plaque sizes. At the inner sclera
surface opposite the center of the tumor base the relative dose is 20-22% of the
Rx dose for all plaque sizes. CONCLUSION: The data provided will be a helpful
tool in evaluating and predicting complications in the retina and sclera based on
the tumor dimensions and selected plaque size.
PMID- 28518504
TI - SU-E-T-557: A Planning Strategy of Volumetric Modulated Arc Therapy with
Simultaneous Integrated Boost for Intracranial Stereotactic Radiotherapy.
AB - PURPOSE: The purpose of this planning study was to evaluate the dosimetric effect
of dose escalation for intracranial stereotactic radiotherapy by volumetric
modulated arc therapy (RapidArc) with simultaneous integrated boost (SIB-VMAT).
METHODS: Dynamic conformal arc therapy (DCA), VMAT, and SIB-VMAT plans using
Novalis Tx (Varian/BrainLAB) were performed for twenty target volumes in patients
with intracranial metastases with median PTV of 16.0 cm3 (range 2.4-35.2 cm3 ).
PTV was created with 2 mm expansion from GTV. All plans were generated with a
prescribed dose of 35 Gy in 5 fractions to the PTV (D95 = 95%), and dose
escalation up to 40 Gy (SIB-VMAT40) and 45 Gy (SIB-VMAT45) was performed only to
the PTV-boost (PTV shrunk by 5 mm) for SIB-VMAT. Each plan was compared using
conformity parameters. RESULTS: The average Paddick conformity index (CI) was
0.78, 0.90, 0.91, and 0.89 for DCA, VMAT, SIB-VMAT40, and SIB-VMAT45,
respectively. The average healthy tissue overdosage factor (HTOF), suggested by
SALT was 0.118, 0.006, 0.007, and 0.011 for DCA, VMAT, SIB-VMAT40, and SIB
VMAT45, respectively. The average V30, V20, and V10 of normal brain for VMAT and
SIB-VMAT decreased by 3.0 cm3 (range 0.1-8.2 cm3 ), 3.0 cm3 (range 0.1-8.7
cm@@@3@@), and 7.5 cm@@@3@@ (range 0.3-26.2 cm@@@3@@), respectively, compared to
DCA depending on the target volume. CONCLUSIONS: SIB-VMAT improved dose
conformity to the PTV for intracranial stereotactic radiotherapy, and decreased
high and low dose volume of normal brain compared to DCA. SIB-VMAT offers the
ability of dose escalation due to high conformity of high dose regions inside the
target volume.
PMID- 28518505
TI - SU-E-T-528: Appraisal of Acorus XB and Convolution Dose Algorithms in Field
Junction of Breast Tangential/superclavicular Fields.
AB - PURPOSE: Dose accuracy injunction regions of breast-tangential therapy is a
challenge, and inaccurate dose predictions may lead to unreal hot/cold spots.
Availability of the novel deterministic radiation transport method Acuros XB
(AXB) provides a potential for more accurate dose predictions. This study
assesses relative dose accuracies of this and the widely used other algorithms:
collapsed cone convolution (CCC) and anisotropic analytical algorithm (AAA)
against film measurements. METHODS: A typical tangential and superclav fileld
combination was planned for an anthropomorphic body phantom using Pinnacle-9.0
treatment-planning system (TPS). The created plan employing 6MV beam was
delivered to the phantom on a Varian linac. In region of the field junction of
tangentials & superclav, films (EBT2) were placed in coronal planes at two depths
(~ 2 and 4 cm). Optical density was measured along and +/- 5mm away from the
field-match line, and converted to dose using film-calibration curve specific to
the batch of film. The same plan was also imported to Eclipse TPS using an import
filter written in MATLAB. Algorithms Pinnacle CCC 9.0, Eclipse AAA 10.0.24 and
AXB 11.0.3 were used for calculations. Comparison of the measured doses (assumed
as gold standard) against doses calculated from planning-systems were preformed
in a MATLAB platform. RESULTS: In general, dose distributions from all three TPS
algorithms are found to agree closely with film data. Agreements between AXB and
CCC dose calculations were found to be reasonable. AXB appears to be better in
modeling the backscatter effects in the heterogeneous regions. AAA calculations
gives acceptable results, but with less accuracy compared to CCC and AXB.
CONCLUSIONS: The novel deterministic algorithm AXB in Eclipse is found to provide
better agreement with measured data in breast-tangential therapy. Benefits of
using Acuors XB algorithm in tangential fields planning requires further
investigation. This work was funded by National Institutes of Health through
grant 2R44CA105806-02 and MD Andersona?TMs Cancer Center Support Grant CA0 16672.
PMID- 28518506
TI - SU-E-T-539: The Effect of the Scattering Volume of Phantom on Dose Calculation
Accuracy Using Elekta's Cone-Beam Computed Tomography (CBCT) for Head-Neck
Radiotherapy.
AB - PURPOSE: To analyze the scattering volume effect of phantom on HU values and dose
calculation accuracy utilizing Elekta's cone-beam computed tomography (CBCT) for
head and neck radiotherapy. METHODS: A water phantom was designed to simulate
different scattering volume by varying its lengthfrom 5cm to 30cm.A CIRS density
reference phantom combined with the water phantom was used to measure the CBCT HU
values. HU-ED correction curves for 30cm length (Correction-A) and 5cm length
(Correction-B) were generated for CBCT dose calculation, respectively. A four
field-box plan was designed both on CBCT and conventional CT of a head-neck
anatomical phantom to compare the dosimetric difference. RESULTS: The maximum HU
variance in the CBCT of the water phantom was up to 10% with varying phantom
length. For the combined CIRS phantom, the HU value in CBCT was found to decrease
in high-density inserts, but increase in low-density inserts with increasing
scatter length.For dense-bone insert, the change in HU values was up to 1422HU.
For head-neck anatomical phantom, the dose results showed an average difference
of 0.3% of cGy /MU, 2-3mm of isodose discrepancy,and 97% of 2%/2mm DTA index for
each beam with Correction-A; and 3.7% of cGy /MU,1.5-3cm of isodose
discrepancy,and 59.5% of 2%/2mm DTA index for each beam with Correction-B.
CONCLUSIONS: The scattering volume of phantom has a significant impact on the HU
value and further HU-D calibration of Elekta's CBCT. Excellent dosimetric
agreement between CBCT and conventional CT was found when the HU-D calibration
phantom volume is close to patient volume imaged by CBCT.
PMID- 28518507
TI - SU-E-T-505: BrainLab Plan Comparisons: Brain Scan Pencil Beam versus IPlan Monte
Carlo.
AB - PURPOSE: Monte Carlo (MC) dose modeling techniques are available in the newest
version of Brain Lab's IPlan treatment planning system (TPS). Prior to the
upgrade, at our facility, BrainLab's BrainScan was the treatment planning system
available; pencil beam (PB) modeling is employed by BrainScan. As published in
the literature, MC calculations, as compared to the PB algorithm, can generate
differences in coverage as much as 20%. With the introduction of the new
treatment planning system, treatment parameter comparisons were made with
quantitative assessments. Differences due to changes in the dose calculation that
could impact patient treatments and outcomes were investigated. METHODS: Beam
data was collected for the new BrainLab TPS IPLAN under the conditions as
outlined in the manufacturer's Version 1.3 data collection, commissioning and
acceptance guidelines. Utilizing BrainLab's treatment planning systems, treatment
plan comparisons were made. First, PB modeling treatment plans were assessed for
each treatment plan with pencil beam modeling in the BrainScan and IPlan TPS.
Treatment plans with MC modeling were then compared to PB models. RESULTS:
Differences in the dose distribution, DVH values, and monitor units were
evaluated between the older version software (BrainScan) and the newer treatment
planning system (IPlan). As predicted by the literature, the differences in the
MC modeling versus PB modeling were significant depending upon the anatomy (tumor
site). Modeling comparison for the treatment plans will be presented for SRS
(Stereotactic Radiosurgery) and Stereotactic Body Radiation Therapy (SBRT).
CONCLUSIONS: Clinical implementation of a new treatment planning system must be
approached with caution and with adherence to AAPM recommendations and
guidelines. Whenever a new TPS calculation model is introduced, thorough
comparison between former and new models should be obtained. An additional
recommended test would be to perform an independent, end-to-end check of the
overall system utilizing the RPC (Radiological Physics Center) phantom.
PMID- 28518508
TI - SU-E-T-550: Influence of the Clinical Outcome and Quality of Life by Replanning
during Intensity-Modulated Radiation Therapy for Nasopharyngeal Carcinoma.
AB - PURPOSE: The purposes of this study were to expound on the benefit of replanning
using clinical outcome and Quality of life (QoL) during Intensity-Modulated
Radiation Therapy (IMRT) for nasopharyngeal carcinoma (NPC). METHODS: A total of
129 new patients with NPC, who were curatively treated by IMRT from June 2007 to
August 2011, were recruited. Eighty-six patients with repeat CT and replanning
and 43 patients non-replanning were retrospectively analyzed. The Chinese version
of the European Organization for Research and Treatment of Cancer Quality of Life
(QoL) Questionnaire C30 and H&N were completed before treatment, the end of
treatment, 1, 3, 6, 12 month after treatment. QoL and Kaplan- Meier estimators
were used to estimate the survival function of patients with or without
replanning. RESULTS: The clinical outcome comparison indicated that replanning
during the IMRT for NPC improved the locoregional control (LRC) (p=0.040), but
did not improved the overall survival (OS) (p=0.475). The 2-year LRC, OS rates
were 92.4%, 82.2%, and 97.2%, 89.8% in non-replanning ans replanning,
respectively. Global QoL (p=0.012) and role functioning (p=0.000) and social
functioning (p=0.000) and dyspnea (p=0.001) and appetite loss (p=0.010) and
constipation (p=0.010) and diarrhea (p=0.010) and speech problems (p=0.000) and
trouble with social contact (p=0.000) and teeth (p=0.031) and opening mouth and
dry mouth (p=0.000) and sticky saliva (p=0.015), have significantly differences
between replanning and non-replanning in patients with NPC. CONCLUSIONS: Our
results indicate that replanning can improve significantly LRC and QoL variables
in patients with NPC. Grant No. 2008B198 from Zhejiang Provincial Medical and
Health science Foundation of China.
PMID- 28518509
TI - SU-E-T-509: Photon Spectrum Modeling of Flattening Filter Free (FFF) Beam and the
Optimization of Model Parameters.
AB - PURPOSE: To determine the distribution of photon spectrum on flattening filter
free (FFF) beams, novel and fast optimization methods that were applicable on a
convolution/superposition dose calculation algorithm were implemented. METHODS:
Two-step optimization method was designed to model the virtual photon spectrums
for FFF beams. At first, simple functional form of photon spectrums proposed by
E. S. M. Ali was modified and used to make rough shapes of photon spectrum. The
distributions of photon spectrums were defined at various field sizes (FSs) to
consider the changes of the contribution for scattered photons. Percent depth
doses (PDDs) at various FSs were used, and collapsed cone convolution (CCC)
algorithm was used to calculate PDDs by considering cone-shaped photon fluence in
fields. At next, an arbitrary functional form of photon spectrums where the
values of photon intensity itself were free parameters was designed. Line search
method was used for optimization and gradient terms at each free parameter were
derived from CCC algorithm to enhance the speed of iterations. RESULTS: The mean
energies of the optimized spectrums were decreased from 1.40 to 1.21 MeV for 6 MV
FFF beams and from 2.45 to 1.27 MeV for 10MV FFF beams as FSs were increased from
3*3 to 40*40 cm2 because of the contributions of scattered photons. The shape of
the spectrums were not greatly changed with field sizes, but root mean squared
differences (RMSDs) between the measured PDDs and the calculated PDDs using
optimized spectrums were increased upto 0.87% as the FSs were decreased to 3*3
cm2 . CONCLUSIONS: Developed method for spectrum modeling showed good agreements
when the PDDs were calculated with the optimized results. Suggested method is
proper to the radiation treatment planning systems because it only requires
measured PDDs, and based on the analytic dose calculation algorithm. This work
was supported by the National Research Foundation of Korea(NRFK)? grant funded by
the Korean government (MEST)? (Grant No. K20901000001-09E0100-00110?), Varian
Medical Systems, NCI Grant No.1R01 CA98523?, and NSF Grant No. 0854492?.
PMID- 28518510
TI - SU-E-T-541: Dose Calculation Algorithm for External Neutron Radiotherapy Based on
Pencil Beam Method.
AB - PURPOSE: To evaluate the availability and performance of pencil beam algorithm
for fast neutrons radiotherapy dose calculations and to achieve improvements in
universality, speed and inhomogeneities corrections. METHODS: Pencil beam (PB)
method uses integration of dose kernel cross field size to estimate dose
distribution. In order to calculate dose kernels we used general purpose Monte
Carlo (MC) code MCNP. The same program was used also for PB benchmarking. Multi
group approach used for kernels calculation virtually allows calculation for
arbitrary spectrum. Nevertheless we took four common spectra to investigate
accuracy and to establish according corrections. Several approaches for
inhomogeneities corrections have been investigated. The output of MC calculations
is discrete kernel data, which does not allow fast calculations. To overcome this
limitation we investigated different dose kernels approximations and
integrations. RESULTS: PB dose kernel library was established. Comparison of PB
calculation with reference algorithm shows adequate precision for arbitrary
neutron spectra with inhomogeneities correction, while calculations are fast
enough for optimization tasks. Secondary photon dose distributions comparison
give worse still promising results. CONCLUSIONS: Researches of this paper show
benefits and limitations of PB method for neutron teletherapy treatment planning.
Calculations made during research allow saying that results of PB method are
generally acceptable. Still additional data are needed to evaluate our results,
probably voxel phantom MC calculations and/or beam data measurements.
PMID- 28518511
TI - SU-E-T-512: Evaluation of Treatment Planning Dose Calculation Accuracy at the
Interface of Prosthetic Devices.
AB - PURPOSE: To evaluate the ability of treatment planning algorithm to accurately
predict dose delivered at the interface of high density implanted devices.
METHODS: A high density (7.6 g/cc) Cobalt-Chromium-Molybdenum hip prosthesis was
molded into an epoxy-based cylindrical leg phantom. The phantom was designed to
be separated in half to access the prosthesis and to place the TLDs. Using MVCT
to image the apparatus, a simple treatment plan was developed using the Philips
Pinnacle treatment planning system. Wires were placed in the molded epoxy to
allow for accurate definition of measurement sites (TLD positions) along the
surface of the prosthesis. Micro-cube TLDs (1 mm3 ) were placed at six
measurement locations for which the dose had been calculated by the treatment
planning system. An Elekta Synergy linear accelerator was used to deliver a 400
cGy plan to the phantom with 6 MV photons in a single fraction. A total of four
10 cm * 21 cm fields were used at 0, 90, 180, and 270 degree gantry rotations.
RESULTS: Initial results indicate that the measured dose is 7-17% lower than the
dose calculated by the treatment planning system. Further study using high energy
beams are also in progress. CONCLUSIONS: Initial results indicate that the
treatment planning system does predict the dose near a high density prosthetic
device within 10-15% but underestimates the dose. The results of this study could
help in designing treatment plans which would reduce the uncertainty of the dose
delivered in the vicinity of prosthetic hip implants and similar devices.
PMID- 28518512
TI - SU-E-T-552: Maximizing the Biological Effect of Proton Dose Delivered with
Scanned Beam.
AB - PURPOSE: Biological effect of radiation can be enhanced with hypofractionation,
localized dose escalation, and controlled distribution of proton's linear energy
transfer (LET). We evaluate potential gain in therapeutic effect from delivery of
daily inhomogeneous fractional dose distributions in pencil beam scanning proton
therapy (PBS-PT). METHODS: For cases of prostate cancer, we considered a
hypofractionated course of 20 fractions of 3 Gy (assuming alpha/beta=1.5, the
equivalent dose in 2-Gy fractions (ED2Gy) is 77.1 Gy). Two sets of dose
distributions were planned using two opposed lateral fields to deliver a uniform
dose: (1) in full-target plans (FTP) each beam targeted the entire gland (2) in
split-target plans (STP), beams targeted only the respective proximal hemispheres
(prostate split sagittally). Linear combinations of optimized beam intensity maps
from FTP and STP, for a variety of mixing weights, were used to evaluate
inhomogeneous fractional dose (IFD) distributions. IFD delivered doses boosting
either hemisphere in alternating fractions, e.g., alternating between 40% and
160% of the nominal fractional dose (1.2-4.8 Gy). The equivalent uniform dose
(EUD) was calculated for ED2Gy distributions. IFD plans were rescaled so that the
EUD of rectum and bladder did not increase. LET distributions were calculated
with Monte Carlo, and compared for different plans. RESULTS: In the IFD courses,
the whole prostate received a nearly uniform dose in every 2 fractions, however
EUD was higher than in conventional FTP by up to 8%. Rectal EUD decreased by 2%,
and bladder EUD was unchanged. The LET distributions of FTP and STP were
distinctly different, thus, in IFD, LET depended strongly on the mixing weights.
CONCLUSIONS: In PBS-PT, modestly improved therapeutic outcome can be expected
with delivery of inhomogeneous daily dose distributions, while administering the
prescribed dose to target over the entire course. The biological effectiveness
may be further enhanced by optimizing the LET distributions. The project was
supported by the Federal Share of program income earned by Massachusetts General
Hospital on C06 CA059267, Proton Therapy Research and Treatment Center.
PMID- 28518513
TI - SU-E-T-523: Modeling Beam Data for Flattening Filter Free (FFF) Photon Beams.
AB - PURPOSE: For flattening-filter free (FFF) photon beams, conventional algorithm
based on equivalent-square to calculate dose per MU is invalid because of the non
uniform profile. In this study, an empirical algorithm is developed to calculate
the dose accurately, which can be used for secondary MU check for IMRT using FFF
beams. METHODS: A kernel-based algorithm based on three parameters (a0, w0, d0)
is used to quantify the phantom scatter characteristics of the photon beam. The
model is modified to quantify the shape of the FFF at off-axis locations by
fitting the primary off-axis ratio (POAR) by a linear function 1 - br, where b is
a constant and r is the radial distance. The resulting parameters are used in a
kernel-based dose calculation algorithm for dose calculation. RESULTS: It is
found that the proposed model can fit the product of the fractional depth doses
(FDD) and phantom scatter factors (Sp) for field sizes between 2 and 40 cm and
depth between 0 and 40 cm to a max and standard deviations of 1.7% and 0.01% and
1.8% and 0.01%, respectively, for 6 and 10 MV FFF beams. The value of b is 0.025
and 0.0323 for 6 MV and 10 MV photons, respectively, from fitting the POAR. The
resulting phantom scatter parameters are consistent with those obtained from MC
simulation. If the slope is not taken into account (b = 0), then the model cannot
fit the central-axis Sp*FDD accurately and resulted in a maximum error of 3% and
4% for 6 and 10 MV, respectively. CONCLUSIONS: We have demonstrated that the
shape of POAR from FFF beam will impact on the dose calculation on the central
axis. Conventional equivalent square law concept will not be applicable for dose
calculation for FFF beams.
PMID- 28518514
TI - SU-E-T-534: Beam and MLC Commissioning and Assessment of Three Commercial
Treatment Planning Systems.
AB - PURPOSE: To assess and compare the open beam and multi-leaf collimator modeling
of Pinnacle, Ecilpse (AAA and Acuros) and RayStation planning systems. METHOD AND
MATERIALS: The 6MV photon beam of a Varian TrueBeam with Millennium 120 MLC was
used for this study. Measurements made with combinations of ion chamber,
radiochromic film, and diodes in water and plastic phantoms. Depth and crossplane
profiles of open square fields shaped by jaws or MLC ranged from 3*3 to 40*40cm2
and from 0 to 20 cm depth. Depth dose, flatness (80% of FWHM), and penumbra (20
80%) of calculated and measured profiles were compared. Various MLC test patterns
were calculated and compared with measurements to assess the modeling of the
round leaf edge, tongue-and-groove, and interleaf transmissions. RESULTS:
Calculated depth doses are within 1.0% and flatness is within 2% for all field
sizes and depths. Jaw penumbrae are within 2mm and 3mm for 20*20 and 30*30cm2 at
10cm depth respectively. MLC penumbrae (20-80%) of the three systems are within
0.3mm and 1.0mm for a 3*3cm2 and 10*10cm2 MLC apertures. Notably, to match the
measured MLC round-edge transmission, the half thickness (10% transmission) leaf
tip width of the current RayStation MLC model has to be broadened to 10mm. All
three systems appear to adequately model the tongue-and-groove. Pinnacle
explicitly models the interleaf transmission while Eclipse and RayStation simply
use average MLC transmission. CONCLUSIONS: All three systems are capable of
generating clinically acceptable beam models for open fields. Based upon the
round-edge profile, Eclipse and Pinnacle provide better MLC models than
RayStation. Among the three systems, Eclipse took the least time and effort to
commission these features.
PMID- 28518515
TI - SU-E-T-545: Dose Comparison between Intravenous Contrast-Enhanced CT and Non
Contrast CT in Treatment Planning.
AB - PURPOSE: With increasing concern for patient dose from CT scan, we are trying to
reduce CT scan and use intravenous contrast-enhanced CT (contrast CT) in
treatment planning. This study is to investigate dose calculation accuracy using
contrast CT in treatment planning for lung, esophagus and pancreas cancer.
METHODS: We analyzed treatment plans for 8 patients for whom CT simulation was
performed both with and without intravenous contrast agent (CA) (non-contrast
CT). IMRT/3D plans were generated with inhomogeneity correction on the non
contrast CT scan. Contrast CTs were fused to the non-contrast studies and all
contours and plans were copied to the contrast CT scans. For each patient, we
analyzed dose-volume histograms (DVH) for planning volumes (PTV) and the organs
at-risk (OAR), comparing the doses generated on non-contrast CT scans with those
generated on contrast CT scans. RESULTS: Maximum doses ratio Dmax(contrast)/Dmax
(non-contrast) in PTVs was 1.0009+/-0.0013. The ratio of D05 (contrast)/D05 (non
contrast) was 0.996+/-0.005. The ratio of mean PTV dose Dmean(contrast)/Dmean(non
contrast) was 0.990+/-0.005%. The ratio of minimum dose Dmin(contrast)/Dmin(non
contrast) and D95(contrast)/D95(non-contrast) were 0.970+/-0.030 and 0.984+/
0.009, respectively. Contrast CT raised cord dose slightly. The ratio of cord
Dmax was 1.005+/-0.026. However there were two cases the ratio of cord Dmax were
1.035. CONCLUSIONS: The PTV D95 is usually normalized to prescription dose and
the D95 differences between contrast and regular CT were within 2%. In most
cases, the contrast CT could be used to treatment planning clinically. However
more attention should be paid to maximum cord dose if it is already close to
criteria limit.
PMID- 28518517
TI - SU-E-T-556: Integration of Lung Blocks in the Inverse Planning Process of
Modulated Arc Total Body Irradiation Using Cone Beam CT.
AB - PURPOSE: The sizing and placement of lung blocks for total-body irradiation (TBI)
is critical to prevent lung toxicities and maintain effective treatments. During
modulated-arc TBI (MATBI) treatment, the patient is stationary near the floor
while open-field beams with varying exposures are delivered. The inverse planning
process currently aims for a uniform dose to the body, without accounting for the
presence of lung blocks. This study investigates the possibility of including the
effect of these blocks in the MATBI optimization process. METHODS: Dosimetric
comparisons were performed using a water tank and a simple stack of solid water
slabs. Lungs blocks made of cerrobend were fabricated and imaged using on-board
megavoltage CBCT (MVCBCT). The reconstructed MVCBCT images were precisely
registered with the reference CT for inverse planning. The cerrobend blocks were
contoured in the planning system and the density was overridden to 9.3 g/cm3 .
Simulated doses in Pinnacle were compared to ion chamber, diode array and gaf
chromic film measurements obtained at 1.0, 5.0, 10.0 and 20.0 cm depths. Specific
optimization objectives on the lungs were tested on 5 patients including a lung
re-treatment. RESULTS: The maximum difference between ion chamber measurements
and the treatment planning predictions was 2.4%. The measurements profiles with
the diode array correlated reasonably well (<5%) with predictions. Gaf-chromic
films demonstrated good accuracy at depth but large differences (>10%) on the
surface. Lung blocks reconstructed with MVCBCT were structuraly accurate without
significant metal artifacts. A comparison of MATBI plans on patients shows that
inclusion of lung blocks during optimization can reduce hot and cold areas in the
lungs and the sternum. CONCLUSION: Reasonable predictions of the lung block
transmission can be obtained following the developed technique using megavoltage
CBCT. Thus, lung blocks can be included in the MATBI inverse planning process,
which can help prevent complications and local failure.
PMID- 28518516
TI - SU-E-T-516: Dosimetric Validation of AcurosXB Algorithm in Comparison with AAA &
CCC Algorithms for VMAT Technique.
AB - PURPOSE: To dosimetrically validate AcurosXB algorithm for Volumetric Modulated
Arc Therapy (VMAT) in comparison with standard clinical Anisotropic Analytic
Algorithm(AAA) and Collapsed Cone Convolution(CCC) dose calculation algorithms.
METHODS: AcurosXB dose calculation algorithm is available with Varian Eclipse
treatment planning system (V10). It uses grid-based Boltzmann equation solver to
predict dose precisely in lesser time. This study was made to realize algorithms
ability to predict dose accurately as its delivery for which five clinical cases
each of Brain, Head&Neck, Thoracic, Pelvic and SBRT were taken. Verification
plans were created on multicube phantom with iMatrixx-2D detector array and then
dose prediction was done with AcurosXB, AAA & CCC (COMPASS System) algorithm and
the same were delivered onto CLINAC-iX treatment machine. Delivered dose was
captured in iMatrixx plane for all 25 plans. Measured dose was taken as reference
to quantify the agreement between AcurosXB calculation algorithm against
previously validated AAA and CCC algorithm. Gamma evaluation was performed with
clinical criteria distance-to-agreement 3&2mm and dose difference 3&2% in omnipro
I'MRT software. Plans were evaluated in terms of correlation coefficient,
quantitative area gamma and average gamma. RESULTS: Study shows good agreement
between mean correlation 0.9979+/-0.0012, 0.9984+/-0.0009 & 0.9979+/-0.0011 for
AAA, CCC & Acuros respectively. Mean area gamma for criteria 3mm/3% was found to
be 98.80+/-1.04, 98.14+/-2.31, 98.08+/-2.01 and 2mm/2% was found to be 93.94+/
3.83, 87.17+/-10.54 & 92.36+/-5.46 for AAA, CCC & Acuros respectively. Mean
average gamma for 3mm/3% was 0.26+/-0.07, 0.42+/-0.08, 0.28+/-0.09 and 2mm/2% was
found to be 0.39+/-0.10, 0.64+/-0.11, 0.42+/-0.13 for AAA, CCC & Acuros
respectively. CONCLUSIONS: This study demonstrated that the AcurosXB algorithm
had a good agreement with the AAA & CCC in terms of dose prediction. In
conclusion AcurosXB algorithm provides a valid, accurate and speedy alternative
to AAA and CCC algorithms in a busy clinical environment.
PMID- 28518518
TI - SU-E-T-527: Assessment of Field-Junction Dosimetry: Pinnacle V9.0 versus Film
(EBT2).
AB - PURPOSE: To investigate dose agreement of Pinnacle V9.0 with measurements across
the junction between abutting photon and electron fields. METHODS: Photon-photon,
photon-electron, and electron-electron field junctions of energies 6 MV and 9 MeV
were evaluated with 0, 5, and 10 mm gaps between the field edges at depths of 2,
15, and 30 mm with Gafchromic film (EBT2). Photon and electron fields (10*10 cm)
were setup to deliver 300 cGy in their field centers to 30 mm depth. Film optical
density was measured every millimeter across the field-junction with a
densitometer (light beam 2 mm). Optical Density to dose conversion was
accomplished using a calibration curve specific to the batch of this film. For
comparison, all field combinations were generated in Pinnacle, and doses were
calculated with collapsed-cone convolution algorithm employing calculation-grid
sizes 2, 3, and 4 mm. RESULTS: Measured doses at junction are as much as 20%
different than Pinnacle calculation. 3 profiles with zero gap, 1 profile with 0.5
cm gap, and 0 profiles with 1.0 cm gap showed a disagreement greater than 12%.
Measurement showed a bias towards higher dose in the junction when compared to
Pinnacle calculation. With dose-calculation grid reduced below 4 mm, Pinnacle
calculations showed improved agreements, but only a few percent at most. Pinnacle
versus measured dose disagreements do not show clear trends with field separation
or depth. CONCLUSIONS: Doses calculated by Pinnacle V9.0 in the field-junction
region may not be accurate for abutting photon and electron fields, particularly
when a coarse dose-calculation grid is utilized. Lack of clear trends in dose
agreement with field separation and depth suggests that uncertainties in other
factors such as jaw positions and phantom set-ups may be additional contributors.
Significant inaccuracies in doses reported by the treatment-planning system in
field-junction region should be considered while making clinical decisions.
PMID- 28518519
TI - SU-E-T-538: Evaluation of IMRT Dose Calculation Based on Pencil-Beam and AAA
Algorithms.
AB - PURPOSE: To evaluate the accuracy of dose calculation for intensity modulated
radiation therapy (IMRT) based on Pencil Beam (PB) and Analytical Anisotropic
Algorithm (AAA) computation algorithms. METHODS: IMRT plans of twelve patients
with different treatment sites, including head/neck, lung and pelvis, were
investigated. For each patient, dose calculation with PB and AAA algorithms using
dose grid sizes of 0.5 mm, 0.25 mm, and 0.125 mm, were compared with composite
beam ion chamber and film measurements in patient specific QA. Discrepancies
between the calculation and the measurement were evaluated by percentage error
for ion chamber dose and gamma>l failure rate in gamma analysis (3%/3mm) for film
dosimetry. RESULTS: For 9 patients, ion chamber dose calculated with AAA
algorithms is closer to ion chamber measurement than that calculated with PB
algorithm with grid size of 2.5 mm, though all calculated ion chamber doses are
within 3% of the measurements. For head/neck patients and other patients with
large treatment volumes, gamma>l failure rate is significantly reduced (within
5%) with AAA-based treatment planning compared to generally more than 10% with PB
based treatment planning (grid size=2.5 mm). For lung and brain cancer patients
with medium and small treatment volumes, gamma>l failure rates are typically
within 5% for both AAA and PB-based treatment planning (grid size=2.5 mm). For
both PB and AAA-based treatment planning, improvements of dose calculation
accuracy with finer dose grids were observed in film dosimetry of 11 patients and
in ion chamber measurements for 3 patients. CONCLUSION: AAA-based treatment
planning provides more accurate dose calculation for head/neck patients and other
patients with large treatment volumes. Compared with film dosimetry, a gamma>l
failure rate within 5% can be achieved for AAA-based treatment planning.
PMID- 28518520
TI - SU-E-T-504: Incident Fluence Reconstruction Based on Monte Carlo Finite-Size
Pencil Beam Model for Dose Guided Radiation Therapy.
AB - PURPOSE: In dose guided radiation therapy, incident fluence is one of the
important parameters for both influence verification and dose reconstruction. The
objective of this investigation was to develop a method to obtain the incident
fluence for dose reconstruction in dose guided radiation therapy (DGRT). METHODS:
An incident fluence reconstruction model based on Monte Carlo Finite-size pencil
beam (MCFSPB) model and "Matthew Effect" Conjugate-gradient (CG) algorithm was
developed, where the MCFSPB model was developed by FDS Team (www.fds.org.cn) and
the "Matthew Effect" was proposed to advance the accuracy of CG lgorithm. Then,
by measuring dose with amorphous silicon flat panel (a-Si flat panel), the
incident fluence was unfolded. An artifical head phantom was used to test sample.
By using the incident fluence to dose calculation with MCFSPB, the 2D and 3D dose
was also reconstructed and compared with the measurement dose and the planing
dose respectively. The Passing Rate of Dose Difference (PRDD) in 3% was used to
learn the accuracy. RESULTS: Two representative cases (6MV and 10MV) with both
five beams were used for beam-by-beam verification, and the corresponding
incident fluence was obtained. By comparing the measurement dose with the
calculation dose on measurement plane, the results showed that the PRDD (3%) in
field was 100%. And by comparing 3D plannning dose with 3D reconstructed dose,
the results indicated that the PRDD (3%) in field was 95%~98%. CONCLUSIONS: The
incident fluence reconstruction model based on MCFSPB model and "Matthew Effect"
Conjugate-gradient algorithm was developed. The tested results indicated its
accuracy. This study is expected to be applied to 3D dose reconstruction and 3D
dosimetric verification in DGRT. Supported by the National Natural Science
Foundation under grant No.30900386 and the National Science Foundation of Anhui
Province (Nos.090413095 and 111040606Q55).
PMID- 28518521
TI - SU-E-T-549: On Importance of Accurate Treatment Couch Modeling in SmartArc VMAT
Plans.
AB - PURPOSE: We investigate the impact of a treatment couch and its modeling in a
treatment planning system on accurate dose delivery in Volumetric Modulated Arc
Therapy (VMAT). METHODS: A cone-beam CT of a Varian couch on a Varian Clinac 21EX
unit, consisting of a carbon-fiber imaging couch top and supporting rails, was
acquired, and a couch model was created in Philips Pinnacle 9.0 TPS based on the
geometry of the couch top and the rails. The densities of the modeled couch top
and the rails were based on the Hounsfield Unit and CT number-to-density
information obtained from the CBCT scan. The densities were then adjusted based
on the ion chamber measurements of a beam transmitting through the couch
posteriorly at different gantry angles varying 1-5 degrees. SmartArc VMAT plans
for patient treatment with and without the modeled couch were then generated and
dose distributions were verified using the IBA MatriXX 2D ion chamber array.
RESULTS: We found that depending on the gantry angle the beam can be attenuated
by up to 17% when going through the supporting rails, and up to 5% when passing
through the couch top. Because of this, dose distributions of SmartArc plans were
not accurate and did not pass the dose verification criteria without accurate
modeling of the treatment couch. Adding the couch model remedies this problem and
avoids underdosing the target. CONCLUSIONS: We showed that the impact of a
treatment couch in radiation therapy can be significant, and it is essential to
include an accurate model of the couch in the treatment planning system,
particularly for SmartArc VMAT plans in Philips Pinnacle TPS.
PMID- 28518522
TI - SU-E-T-520: Quantitative Evaluation of Metal Artifacts in CT and Cone-Beam CT
Images on the Accuracy of Dose Calculation.
AB - PURPOSE: To investigate effects of metal artifacts on the dose calculation
accuracy of three dose calculation algorithms on CT and cone-beam CT images.
METHODS: A phantom with and without metal objects was scanned using CT simulator
and on-board kV CBCT. Conformal 5-field treatment plans with identical physical
and dosimetric parameters were created in the EclipseTM treatment planning system
for CT and CBCT images. The beams were designed to avoid entering through
metallic object. Three dose calculation algorithms were used in the plans: (a)
pencil beam convolution with modified Batheo (PBC-MB), (b) equivalent TAR (PBC
ET), and (c) analytical anisotropic algorithm (AAA). The dose calculation on the
phantom CT images without metal was used as reference to compare with doses
calculated using scans with metal objects. The gamma analysis and percentage dose
differences were used to quantify the dosimetric effects of image artifacts from
metal on CT and CBCT numbers. RESULTS: The dose difference analysis shows that
mean percentage dose differences (MPDD) for CBCT with metal artifacts ranged from
-0.12% to -0.26% with an average of -0.20% for PBC-MB, -0.25% to -0.39%, with
average -0.31% for PBC-ET, and -0.25 to -0.84%, with average -0.62% for AAA for
all planes. The PBC-MB showed the least difference in dose and highest gamma
passing rates with the AAA consistently having the highest differences and lowest
gamma passing rates. This might result from accurate consideration of scattered
dose in heterogeneities by AAA. All MPDD for doses calculated on CT and CBCT
using different dose calculation algorithms were not significant (within 1%).
CONCLUSION: The image artifacts due to streaking from metal objects were
generally small (within 1%) for the dose calculated using the different treatment
planning algorithms on CT and CBCT images. Furthermore, the dose difference from
CT-number variation between CBCT and CT were negligible.
PMID- 28518523
TI - SU-E-T-508: A Novel Method of Heterogeneity Compensation for the Convolution /
Superposition Algorithm.
AB - PURPOSE: We developed a better method of accounting for the effects of
heterogeneity in convolution algorithms. We integrated this method into our GPU
accelerated, multi-energetic convolution/superposition (C/S) implementation. In
doing so, we have created a new dose algorithm: heterogeneity compensated
superposition (HCS). METHODS: Convolution in the spherical density-scaled
distance space, a.k.a. C/S, has proven to be a good estimator of the dose
deposited in a homogeneous volume. However, near heterogeneities electron
disequilibrium occurs, leading to faster fall-off and re-buildup than predicted
by C/S. We propose to filter the actual patient density in a position and
direction sensitive manner, allowing the dose deposited near interfaces to be
increased or decreased relative to traditional C/S. We implemented the effective
density function as a multivariate first-order recursive filter. We compared HCS
against traditional C/S using the ICCR 2000 Monte-Carlo accuracy benchmark, 23
similar accuracy benchmarks and 5 patient cases. For the patient cases, we
created custom routines capable of using the discrete material mappings used by
Monte-Carlo. C/S normally considers each voxel to be a mixture of materials based
on a piecewise-linear density look-up table. RESULTS: Multi-energetic HCS
increased the dosimetric accuracy for the vast majority of voxels; in many cases
near Monte-Carlo results were achieved. HCS improved the mean Van Dyk error by
0.79 (% of Dmax or mm) on average for the patient volumes; reducing the mean
error from 1.93%|mm to 1.14%|mm. We found a mean error difference of up to 0.30
%|mm between linear and discrete material mappings. Very low densities (i.e. <0.1
g / cm3 ) remained problematic, but may be solvable with a better filter
function. CONCLUSIONS: We have developed a novel dose calculation algorithm based
on the principals of C/S that better accounts for the electron disequilibrium
caused by patient heterogeneity. This work was funded in part by the National
Science Foundation under Grant No. EEC9731748, in part by Johns Hopkins
University internal funds and in part by Elekta.
PMID- 28518524
TI - SU-E-T-511: Dose Variations Related to Tumor Size and Location for Pencil Beam
and Anisotropic Analytical Algorithms.
AB - PURPOSE: To investigate the tumor geometric relationship to the dose variations
of Anisotropic Analytical Algorithm (AAA), pencil beam convolution algorithm
with/without modified Bath Power Law(PBMPL)/PB in stereotactic body radiation
therapy(SBRT) treatment plans of patients presenting with a solitary primary lung
cancer. MATERIALS/METHODS: Treatment plans of 14 patients (7 upper lobe, 7 lower
lobe) were used for this study. The planning target volume (PTV) size ranges from
3.9c.c. to 156.7c.c. The SBRT treatment plans were composed of 10-12 non-
coplanar photon beams as per RTOG guidelines. The prescription dose for this
study were (i) 4*12Gy, (ii) 5*10Gy, and (iii) 5*11Gy. The Varian Eclipse
treatment planning system Eclipse v. 8.9 (Palo Alto, CA) was used for this study.
Four-dimensional CT (4D CT) data were used to define the integral target volume
(ITV) on maximum intensity projection. An 5mm circumferential margin was used to
create PTV from ITV. Plans were generated with three algorithms. RESULTS: a). For
small lesions (PTV occupy less than 1% of the ipsilateral lung volume), the PBMPL
plans had overestimated the dose by average 10% compared to AAA. But the PB
without any heterogeneity correction agrees well with AAA. b). For big lesions
(PTV occupy more than 1% of the ipsilateral lung volume), the PBMPL plans had
agreed well with AAA. But the PB without any heterogeneity correction
underestimate the dose by average 15% compared to AAA. c). The tumor location
(Group1: within 1cm from the lung wall;Group2: 2cm away from the lung wall
Group3: in between zone of 1 and 2cm from the lung wall; Group 4:Spread from the
lung wall to the 2cm away zone) seems to relate with dose calculation variations
among different algorithms. CONCLUSIONS: Prescription adjustment is not necessary
for PTV less than 1% of ipsilateral lung volume as the recent suggestion by the
quality assurance working group of phase III Rosel study of prescription dose
reduction of 10% from 60Gy to 54Gy when utilizing AAA instead of PBC.
PMID- 28518525
TI - SU-E-T-551: A Customized Plan Evaluation System for On-Line Adaptive
Radiotherapy.
AB - PURPOSE: Treatment plan evaluation based on daily images, to determine whether it
is necessary to re-plan the treatment, is an essential element of adaptive
radiotherapy. A fully automatic system, incorporating physician preferences and
requirements of specific protocols quantified by a series of objective functions,
was developed to evaluate treatment plans. METHODS: The evaluation system was
developed using IDL 6.1 (ITT Visual Information Solutions, Boulder, CO). Based on
customized evaluation guidelines, dosimetric parameters, including maximum dose,
minimum dose, uniformity dose, dose coverage, conformity index, heterogeneity
index, gEUD, and DVH for the targets and OARs are evaluated as series of cost
functions which incorporate specific protocol constraints and physician
requirements. The evaluation system was applied to IMRT plans of head/neck cancer
patients. The Pinnacle Treatment Planning System (research version 9.0) was used
to generate verification treatment plan trials, with image datasets, ROI
structures, and dose distributions exported to evaluation system. RESULTS:
Results show that the evaluation system can complete evaluation of a dose plan
within 2~8 seconds. The system is capable of displaying and comparing dose
distributions among different plans. It also demonstrates great flexibility in
customizing cost functions based on physician preferences. This system is
supported with various user-friendly options, graphical displays, and feasibly
structure in adding new modules. CONCLUSIONS: This evaluation system is capable
of quantifying specific protocols and preferences of physicians and completing
automatic evaluation almost in real-time. It is an essential a platform for
adaptive radiation therapy and also valuable for initial treatment planning. This
research is supported by CPRIT Individual Investigator Award RP110329.
PMID- 28518526
TI - SU-E-T-522: Analysis of SCERMA-to-KERMA Ratio for Megavoltage Photons.
AB - PURPOSE: To examine the relationship between the primary SCERMA, Sp, and the
primary collision KERMA, Kcp, as a function of depth for clinically relevant
energy spectra, and to accurately model the SCERMA to KERMA ratio (SKR) for
clinical photon beams. METHOD AND MATERIALS: Sp, Kcp, Sp / Kcp (=SKR) for the
energy spectra of Cobalt-60 (Co-60), and Mohan 4 MV, 6 MV, 10 MV, 15 MV, and 24
MV photons are analytically calculated over depths from 0 to 40 centimeters in
water. The Sp and Kcp are fitted to exponential functions, Sp0exp(-MU'd(l-eta'd))
and Kp0exp(-MUd(l-etad)), respectively, with depth d, linear attenuation
coefficient MU and beam hardening coefficient eta; MU' and eta' are the
corresponding quantities for Sp. The relationships between MU', eta', and SKR vs.
MU are examined. Trends between the fitting parameters and MU were also
determined, and the results applied to model the SKR of 6* and 15* clinical beams
as functions of only MU, eta, and depth. RESULTS: SKR decreases with depth for
all spectra. We found MU' = (0.80496 + 4.8748MU)MU + 0.005736 and eta' = (
0.13076 + 2.6571MU)MU + 0.0036151 for 0.0273/cm<=MU<0.0392/cm, and MU' =
0.87718MU + 0.010864 and eta' =(-0.009 - 0.50122MU)MU + 0.0037 for 0.0392/cm <=
MU <= 0.0667/cm. This model predicts the normalized SKR/(SKR(d=0)) with a
relative deviation of 0.1% and max deviation of 1%. SKR/(SKR(d=0)) from clinical
beams 6* and 15* is examined to be in agreement with analytic computation from
spectral data with 1% and 0.5% maximum error, respectively. CONCLUSION: Knowledge
of normalized SKR is a necessary to calculate scatter dose accurately. We have
developed an empirical model to calculate the normalized SKR to be used for
clinical (scatter) dose calculation and consequently improve dose calculation
accuracy.
PMID- 28518527
TI - SU-E-T-533: Evaluating Effective Source Position Corrections during Modeling with
Pinnacle Version 9.2 Software for Flattening Free (FFF) Small Field Treatments.
AB - PURPOSE: Advanced treatment delivery techniques require more robust treatment
planning system (TPS) models for accurate dose planning and computation. As
stereotactic body radiation therapy (SBRT) and volumetric-modulated arc therapy
(VMAT) treatments become more prevalent, the ability of the TPS to accurately
calculate dose delivered from small fields becomes of greater importance. An
additional level of complexity in photon beam modeling is added with the
inclusion of flattening filter free (FFF) treatment beams, due to steep in field
dose gradients and non uniform penumbra regions. The purpose of this work is to
examine the ability of ADAC/Pinnacle TPS to accurately model and calculate dose
from small field FFF treatment beams. METHODS: Photon beam data was first modeled
using Pinnacle v9.0. Flattened and FFF beam models were generated for 6MV and
10MV energies. Models were fine-tuned using a 5*5 cm2 field as the standard field
in order to place more emphasis on the accuracy of the model for the small
fields. An upgrade to Pinnacle v9.2 allowed for comparison between version 9.0
and version 9.2. RESULTS: Accurately modeling small fields using Pinnacle v9.0
proved difficult, particularly in the lower penumbra region. An asymmetry
appeared in the small field models for both the flattened and FFF models. The
Pinnacle v9.2 upgrade eliminated the small field asymmetries, and allowed for
more accurate penumbra region calculations. Preliminary results have shown that
Pinnacle v9.2 is capable of developing accurate beam models when an emphasis is
placed on the small fields. In addition, patient specific dosimetric information
for version 9.0 and version 9.2 was also calculated and examined for prostate,
head & neck, and lung treatments. CONCLUSIONS: Pinnacle v9.2 showed improved
accuracy in small field FFF dose modeling over version 9.0. Comparison of patient
dosimetric information reflected the improvement in the small field modeling.
PMID- 28518528
TI - SU-E-T-544: Commissioning and Clinical Evaluation of a Secondary Check Software
for 3D Conformal and IMRT Treatment Plans.
AB - PURPOSE: The increasing complexities of the geometry of 3D radiation treatment
plans possess challengesto the monitor unit (MU) and dose verification in
clinical routine. In this work, the commissioningof the DIAMOND software (PTW
Freiburg Germany) for two Siemens linear accelerators(Primus & Artiste) along
with the evaluation of its performance is described. METHODS: DIAMOND employs the
modified Clarkson integration method for dose computation and a pointeye-view
(PEV) method for scatter calculation on collimators by a geometrical back
projectinginto the collimation system from the view of the source. During the
commissioning process, themachine data (geometrical set up) and dosimetry base
data such as the percentage depth dose(PDD), head scatter factor Sc as well as
total scatter factor Sc,p, off-axis profiles are entered into the software. A
comprehensive validation process is performed following the provided protocol.For
evaluation purposes, twelve 3D conformal treatment plans and two prostate IMRT
plans arecalculated with DIAMOND and the results are compared to the values from
the treatmentplanning system (TPS). RESULTS: The deviations of the MU for 3D
conformal treatment plans computed with the DIAMONDsoftware are within +/-3%. For
IMRT plan verification, the dose at a point in the target volume iscomputed for
every treatment beam, with deviations within 0.40% to 3.28%. The typical time
forsingle dose point verification is less than a minute, thus minimizing the
clinical workload of theverification process. For dose matrices calculation at
certain plane, a relative longercomputation time is needed depending on a field
dimension. CONCLUSIONS: In this work, we have demonstrated the ability of the
DIAMOND software to compute MU anddose at a point for 3D conformal and IMRT
plans. Its speed and accuracy implies that DIAMOND can be implemented as
independent secondary check software in the clinical routine.
PMID- 28518529
TI - SU-E-T-515: Comparison of Two Dose-Specification Methods for the Treatment of
Uterine Cervix Cancer with HDR Brachytherapy Using a Tandem and Ring Applicator.
AB - PURPOSE: To compare the dose to the high-risk clinical target volume (HRCTV)-D90
and dose-limiting structures with the dose prescription to point A (Manchester
system) using conventional methods to image-guided treatment planning with dose
optimization and a dose prescription to D90 of the HRCTV. METHODS: CT-MR-fused
image sets for 16 patients (stage IA2-IIIB) with uterine cervix cancer were
obtained for each of 5 fractions of HDR brachytherapy using tandem and ring
applicators to generate 2 sets of plans. In the first set, the dose was
prescribed to point A with a standard dwell weight pattern reflecting the
Manchester system loading pattern. In the second set, the dose was prescribed to
D90 of the HRCTV with graphical plan optimization. Parameters of clinical
significance (HRCTV-D90 and dose received by 1.0, 2.0, and 5.0cc of the bladder,
rectum, and sigmoid) were compared, as recommended by GEC-ESTRO. RESULTS: HRCTV-V
for 6 patients was =30cc (largest radius, <2.0cm) and >30cc (largest radius,
=2cm) for the others. For the first set of plans, when HRCTV-V was <30cc, the
ratio of doses HRCTV-D90/dose to point A varied from 1.10 to 1.40. When HRCTV-V
was >30cc, it varied from 0.75 to 0.95. In the second set of plans, HRCTV-D90
always received the prescription dose. Doses to 2cc of one or more organs at risk
exceeded >10% of the limiting doses for 9 patients in the first set of plans but
remained <10% in all patients in the second set of plans. A 10-25% dose reduction
to 2cc of the bladder and 15-35% to 2cc of the rectum and sigmoid occurred in the
second set of plans. CONCLUSIONS: Image-guided brachytherapy with dose
optimization yields a prescribed dose to the HRCTV-D90 while maintaining doses to
organs at risk close to their limiting value, offering a dosimetric benefit over
the traditional method.
PMID- 28518530
TI - SU-E-T-555: Weighted Four-Dimensional IMRT Planning for Dynamic MLC Tracking
Using a Practical and Simple Framework.
AB - PURPOSE: We present a simple, practical framework for truly 4D lung IMRT planning
based on a weighted individual-phase optimization paradigm. This strategy is
specifically developed for use in real-time tumor tracking delivery systems so as
to utilize respiratory motion as an additional degree of freedom rather than a
constraint. METHODS: A 4D-CT scan from a lung SBRT patient was loaded into the
Eclipse treatment planning system. The target and normal structures were manually
contoured on each of the ten phases. For each phase, the total dose prescription
was scaled by the number of phases and a seven-field plan was developed. An open
source deformable image and dose registration engine (DIRART) was used to deform
the dose map at each phase to a reference phase. DVH data from the individually
optimized phase plans were input into an in-house linear programming-based
optimizer implemented in MATLAB, in order to determine dose-weighting factors for
each phase. The objective function aimed to maintain PTV coverage while keeping
normal structure dose as low as possible. This weighted-4D plan (W-4D) was
compared to an ITV-based plan and a 4D plan with equal dose-weights to individual
phases (E-4D). RESULTS: The W-4D dose fractions were determined to be 0.33, 0.01,
0.65 and 0.02 at phase 0%, 30%, 40%, and 90%, respectively (and zero elsewhere).
PTV coverage (V95) was close to identical for all three strategies. The W-4D plan
exhibited mean lung dose 18.8% and 8.5% lower and mean liver dose 23.3% and 5.7%
lower than corresponding values from ITV-based and E-4D plans, respectively.
CONCLUSIONS: By significantly improving normal structure sparing while
maintaining PTV coverage, weighted 4D planning represents a more attractive
solution than ITV-based planning for (currently investigational) real-time tumor
tracking-based delivery systems.
PMID- 28518531
TI - SU-E-T-526: Evaluation of Dose Mapping Errors via Use of a Volume-Based Dose
Mapping Method.
AB - PURPOSE: To quantify dose mapping errors (DMEs) of a point-based dose mapping
method for 4D lung treatment plans. METHODS: Point-based dose mapping methods
utilize deformation vector fields (DVFS) to interpolate dose from a deformed
image. Volume-based dose mapping methods consider the volume overlap between
deformed and reference voxels; defining dose as the integral energy divided by
the integral mass of the voxel, and conserving integral dose . DME is defined as
the dose differences between volume-based and point-based mapped dose
(DME=(DpointBased-DvolumeBased)/DRx). The DME for a 4D lung case is compared with
a bitmap DME method, both using a Pinnacle research version 8.1y DVF. DME is
computed for ten 4D lung cases (five 10 phases, five 3 phase) with Pinnacle
research version 9.100 DVFs. Multi-phase accumulated 4D DMEs are also evaluated.
RESULTS: For all cases, the largest DMEs are located in the dose/density gradient
regions. With Pinnacle 8.1y DVF, mapping dose from phase 9 to phase 0, results in
a DME=-0.2%+/-6.1% (range of -76%~112%). The same case with Pinnacle 9.100 DVFs,
DME=0.3%+/-4.8%(-41%~32%). Locations of large DME are consistent with those from
the bitmap method. For the ten 4D lung cases, accumulated mean DME are within +/
0.07% (std. deviations: 1~5%, range -102%~64%). Maximum tumor DMEs are less than
30cGy (DRx=7200cGy) for all patients. CONCLUSIONS: Due to its inherent integral
dose conservation, volume-based dose mapping methods can quantify errors in point
based dose mapping methods. While mean DME values are small for the cases tested,
standard deviations near 5% indicate that a substantial number of voxels have ~5%
dose mapping errors, however these dose errors do not occur in the target
structures. Work supported by NIH P01CA116602.
PMID- 28518532
TI - SU-E-T-537: Photon Beam Modeling and Verification of Collapsed Cone Convolution
Algorithm for Dose Calculation in a Radiation Treatment Planning System.
AB - PURPOSE: The aim of this study is to evaluate the accuracy the collapsed cone
convolution (CCC) algorithm for dose calculation in a radiation treatment
planning system (TPS). METHODS: We modeled various photon beams for various setup
conditions in a radiation treatment planning system (CorePLANTM, Seoul C&J,
Korea). The beam models were generated at various set-up conditions such as open
beam or wedged beam, 6 MV or 15 MV beam and field sizes from 4*4 cm2 to 40 * 40
cm2 . Each beam model was optimized by spectrum modeling from measured percent
depth dose (PDD) data, dose profile modeling from a measured profile at a
specific depth (10 cm) data. Dose calculation was performed using conventional
CCC algorithm. All measured data were acquired from a Clinac 21EX (Varian Medical
System, Palo Alto, CA, USA) linear accelerator with the setting of SSD = 100 cm.
All calculated PDD and dose profiles at various depths from generated beam models
were compared to the measured data. RESULTS: Calculated dose data from each beam
model showed good agreements within 2% of difference to the measured PDD and
within 3% dose profiles at various depths. Some regions such as penumbra region
at 20 * 20 cm2 field size and horn region at wedge field showed dose
discrepancies over 3%. The results of PDD at all situations showed well agreement
with measured data under the 10*10 cm2 field size. For wedged cases, however,
under the 5 cm depths, some inconsistency at penumbra region were appeared.
CONCLUSIONS: In this study, we verified the accuracy of CCC algorithm in the TPS.
Calculated results by our implemented algorithm was well satisfied with measured
dose at small field size (<20 7 times; 20 cm2 ). Our next study will perform to
compensate theses inconsistencies.
PMID- 28518533
TI - SU-E-T-503: IMRT Optimization Using Monte Carlo Dose Engine: The Effect of
Statistical Uncertainty.
AB - PURPOSE: With the development of ultra-fast GPU-based Monte Carlo (MC) dose
engine, it becomes clinically realistic to compute the dose-deposition
coefficients (DDC) for IMRT optimization using MC simulation. However, it is
still time-consuming if we want to compute DDC with small statistical
uncertainty. This work studies the effects of the statistical error in DDC matrix
on IMRT optimization. METHODS: The MC-computed DDC matrices are simulated here by
adding statistical uncertainties at a desired level to the ones generated with a
finite-size pencil beam algorithm. A statistical uncertainty model for MC dose
calculation is employed. We adopt a penalty-based quadratic optimization model
and gradient descent method to optimize fluence map and then recalculate the
corresponding actual dose distribution using the noise-free DDC matrix. The
impacts of DDC noise are assessed in terms of the deviation of the resulted dose
distributions. We have also used a stochastic perturbation theory to
theoretically estimate the statistical errors of dose distributions on a
simplified optimization model. RESULTS: A head-and-neck case is used to
investigate the perturbation to IMRT plan due to MC's statistical uncertainty.
The relative errors of the final dose distributions of the optimized IMRT are
found to be much smaller than those in the DDC matrix, which is consistent with
our theoretical estimation. When history number is decreased from 108 to 106, the
dose-volume-histograms are still very similar to the error-free DVHs while the
error in DDC is about 3.8%. CONCLUSIONS: The results illustrate that the
statistical errors in the DDC matrix have a relatively small effect on IMRT
optimization in dose domain. This indicates we can use relatively small number of
histories to obtain the DDC matrix with MC simulation within a reasonable amount
of time, without considerably compromising the accuracy of the optimized
treatment plan. This work is supported by Varian Medical Systems through a Master
Research Agreement.
PMID- 28518534
TI - SU-E-T-548: Case Study of HDR Vs IMRT in Pediatric Sarcomas.
AB - PURPOSE: To compare the dose to critical structures using HDR brachytherapy
versus IMRT in pediatric tumors. METHOD: Two sarcoma cases, for which both HDR
and IMRT could be options, were selected for this case study. Case 1 targeted a
volume on the posterior neck/upper back with an HDR prescription of 600cGy * 5
fractions, 3000cGy total. The IMRT prescription used was 180cGy * 25 fractions,
4500cGy total with a boost of 180cGy * 6 fractions, 1080cGy. The IMRT PTV used
was a 0.5cmexpansion of the HDR PTV; the boost PTV was identical to the HDR
treatment plan. Case 2 targeted a volume on the palette of the mouth with an HDR
prescription of 300cGy * 12 fractions, 3600cGy total. The IMRT prescription used
was 180cGy * 28 fractions, 5040cGy total. A 0.5cm expansion of the HDR PTV was
used for the IMRT PTV. In both cases, for both HDR and IMRT, at least 95% of the
PTV received 100% prescription dose, following Children's Oncology Group
protocols. RESULTS: Case 1 : the mean doses to the body, brachial plexus,
esophagus, spinal cord and thyroid were higher using IMRT than HDR. Integral dose
was 6.6 times higher using IMRT than HDR. Case 2: the mean doses to the body,
mandible, and parotids were higher using IMRT than HDR. Integral dose was 2.9
times higher using IMRT than HDR. CONCLUSION: This study shows the potential
benefit of treating with HDR compared to IMRT in select pediatric cases. These
results suggest that HDR can be superior to IMRT in the sparing of critical
structures and in delivering less integral dose to the patient while still
achieving adequate target coverage. However, lower mean doses to critical
structures must also be weighed against the possibility of complications from
HDR's very high hotspots.
PMID- 28518535
TI - SU-E-T-519: Experimental Evaluation of Deterministic Acuros XB Radiation
Transport Algorithm for Heterogeneity Dose Calculation Using the Radiological
Physics Center's Lung Phantom.
AB - PURPOSE: To evaluate the heterogeneity corrected dose calculations from the
Acuros XB (AXB), a novel deterministic dose calculation algorithm based on grid
based Boltzmann transport equation solver (GBBS), for IMRT and VMAT plans.
METHODS: The Radiological Physics Center's lung phantom was used to create
clinically equivalent IMRT and VMAT plans (RapidArc) with the Eclipse planning
system 10.0 that were delivered using a Varian 23 iX. Absolute doses and relative
dose distributions were measured with thermoluminescent dosimeters (TLDs) and
radiochromic film. The measured dose distributions were compared with calculated
doses from both AXB (11.0.3) and AAA (10.0.24) dose calculation algorithms. The
AXB calculated dose-to-water and dose-to-medium were both compared to
measurements. Gamma analysis (+/-7%/4mm, +/-5%/3mm, and +/-3%/3mm) was used to
quantify correspondence between AXB dose distributions and the film measurements.
The computation time between AAA and AXB were also evaluated. RESULTS: For TLD
point doses, both AAA and AXB heterogeneity corrected dose calculations are
within 5% inside the PTV for both IMRT and VMAT plans. The agreements observed
between the measured and calculated doses for both AXB dose reporting methods are
better than those observed with the AAA algorithm. The gamma analysis showed that
the differences between AAA, AXB and film measurement met the RPC +/-7%/4 mm
criteria. The percent of pixels passing rate for both the AXB dose to medium and
AXB dose to water are higher than AAA. The computation time between AAA and AXB
are comparable for IMRT plans but AXB is significantly faster (4 times) than AAA
for VMAT plans. CONCLUSIONS: The AXB implemented in the Eclipse planning system
calculates a more accurate heterogeneity corrected dose than the AAA algorithm as
compared to measurement in lung and improve the calculation speed for VMAT
radiotherapy. Work supported by grants CA10953, CA81647, 2R44CA105806-02,
CA016672 (NCI, DHHS).
PMID- 28518536
TI - SU-E-T-530: Relative Electron Density Phantom Comparison.
AB - PURPOSE: Modern treatment planning systems require lookup tables to convert
Hounsfield Units (HU) to relative electron density (RED) for use in heterogeneity
corrections during dose calculations. The purpose of this work is to illustrate
the impact of using different model CT phantoms to determine HU to RED curves for
treatment planning. METHODS: A GAMMEX model 467 tissue characterization phantom
and a CATPHAN model 500 multipurpose CT phantom were imaged using CT scanners in
four different cancer centers and the HU to RED curves derived from each phantom
were imported into an Eclipse 8.10 treatment planning system. Dose calculation
were performed on a heterogeneity phantom and then compared to measurements. A
comparison of isodose and DVH were performed by calculating 3D and IMRT plans
onto identical CT datasets with different HU to RED curves to determine the
clinical significance. Analysis based on effective atomic number of the phantom
inserts was also performed. RESULTS: The HU to RED curves from the GAMMEX and
CATPHAN phantoms were found to be reasonably self-consistent across the different
CT scanners. However, observable differences for higher density materials were
observed between the two phantom models. The differences for the larger HU values
can be attributed to the effective atomic number of the materials. In kV range of
a CT scanner x-ray spectrum, photon interactions are partially due to the
photoelectric effect which has a larger dependence on atomic number than Compton
scatter which depends most directly on electron density. CONCLUSION: The HU to
RED curve is more dependent on the phantom model than CT scanner. The HU to RED
curve from the GAMMEX phantom produced better agreement between Eclipse AAA
calculations and measured dose distributions on a heterogeneity phantom than that
from the CATPHAN. However, DVH and isodose data on patient plans show small
differences for common treatment sites.
PMID- 28518537
TI - SU-E-T-507: Dose Calculation Quality of AcurosXB Involving a HD120 MLC Compared
with Monte Carlo Methods.
AB - PURPOSE: Advanced radiation therapy requires highly sophisticated dose
calculation algorithms such as finite element based Boltzmann solvers or Monte
Carlo (MC) methods. MC is commonly accepted as the golden standard method for
dose calculation in high energy treatments and thus it is used for benchmarking
other algorithms. In this work the quality of dose distribution calculated using
the Boltzmann solver based AcurosXB algorithm within Eclipse (Varian Medical
Systems) is investigated for volumetric modulated arc treatment (VMAT) plans
involving the high definition MLC (HD120 MLC) by comparing doses with the
validated Swiss Monte Carlo Plan (SMCP). MATERIALS & METHODS: Within SMCP and
Eclipse using AcurosXB, 10 VMAT H&N patient plans and corresponding verification
plans were recalculated using fixed MUs. In SMCP, radiation transport and dose
calculation were performed using VMC++ with a statistical uncertainty of 1%. The
voxel size was 2.5 mm for SMCP and AcurosXB and the same material composition
data was used for CT conversion. Dose volume histograms (DVH) were used in order
to quantify the difference between the dose distributions of the patient plans.
In addition, calculated verification plans were compared with measurements
carried out with the Delta4 system (Scandidos) by using the gamma evaluation with
3%/3 mm criteria of points having a dose larger than 20% of isocenter dose.
RESULTS: DVHs for the patient plans showed good agreement between SMCP and
AcurosXB calculations. Overall AcurosXB lead to an underestimation of the median
dose values by about 1%. For measured total dose distributions of the
verification plans on average 98.6% and 99.0% of the points fullfil the gamma
criteria for the dose calculated using AcurosXB and SMCP, respectively.
CONCLUSIONS: Resulting AcurosXB dose distributions for VMAT H&N plans involving a
HD120 MLC are in good agreement with calculated SMCP dose distributions. CONFLICT
OF INTEREST: This work was supported by Varian Medical Systems.
PMID- 28518657
TI - TU-E-BRB-11: End-To-End Positioning Quality Assurance for Image-Guided
Radiosurgery of Multiple Targets Using a Single-Isocenter.
AB - PURPOSE: Using a single isocenter significantly reduces delivery times in
radiosurgery involving multiple targets. However, because not every target can be
placed at isocenter with this type of treatment, a conventional Winston-Lutz test
cannot be used. We describe a novel Winston-Lutz like mulitarget test (MTT) for
verifying accurate positioning. METHODS: A target phantom, comprised of an
acrylic plate with recesses for three 3/4" spheres was constructed and a high
resolution (0.5*0.5*0.8 mm) CT scan obtained with PTFE spheres placed in the
recesses. The scan was imported into a commercial treatment planning system and
multiple beams were prepared, having their isocenter at the centroid of the
arrangement of spheres. Every beam incorporated three MLC-defined rectangular
apertures that circumscribed the spheres. Custom software selected setup
parameters (table, gantry and collimator angle, MLC openings) such that the
spheres were centered as precisely as possible within their respective MLC
fields, considering the discrete width of collimator leaves. The phantom, with
the PTFE replaced by steel spheres, was placed on the treatment couch and imaged
using stereoscopic x-ray beams. A 6 degree-of-freedom robotic couch applied
translations and rotations to reproduce the CT position. A MV EPID rendered
images of the spheres within their respective apertures, allowing identification
of sphere and aperture centers. Any error upstream would manifest itself as
inaccurate centering of a sphere. RESULTS: Eight beams with table angle 0 and two
beams each with table angles 49.7, 89.8, 272.3, and 310.1 were selected. The
maximum calculated distance between any sphere and the respective aperture center
was 0.07 mm. The median difference measured from the MV images ranged from 0.1 mm
to 1.4 mm with a median of 0.8 mm. CONCLUSIONS: The MTT is a practical end-to-end
test for quality assurance of the entire positioning process in multitarget
radiosurgery, from CT scanning to beam delivery.
PMID- 28518538
TI - How does the pattern of aeroallergen sensitization change over time across all
ages?
AB - BACKGROUND: Identification of aeroallergen sensitization is important for
diagnosis and management of allergic diseases. Immunoglobulin E (IgE)
sensitization status is known to change over time. However, few studies have
explored changes in sensitization patterns across all age groups. The aim of the
present study was to evaluate the changing patterns of in vitro IgE sensitization
tests in allergic rhinitis patients across all age groups. METHODS: We recruited
all patients who were diagnosed as having rhinitis and who underwent in vitro IgE
sensitization testing from 2007 to 2016. Of these, we included 138 who underwent
repeat testing. We analyzed epidemiological data and allergen sensitization
patterns. RESULTS: Of all patients, 56.5% of exhibited changes in allergen
sensitization patterns. The allergens to which all age groups were sensitive were
most commonly mites, with the exception of patients aged 40 to 59 years. The age
group in which "new sensitization," composed of those with "newly developed
sensitization" and "sensitization to more allergens," was most frequent was the 2
to 12 years old group, followed by the 20 to 39 years old group. The age group in
which "desensitization," composed of those with "negative conversion" and
"desensitization to fewer allergens," was most prevalent was the 20 to 39 years
old group followed by the 13 to 19 years old group. Grass pollen was the most
common newly-sensitized allergen and also the most common desensitized allergen.
CONCLUSION: IgE sensitization to aeroallergens can change in individuals with
allergy. These changes may be different according to the patient's age. If
rhinitis symptoms or treatment efficacy changes, repeat IgE sensitization testing
is needed to find changes in allergen sensitization patterns.
PMID- 28518658
TI - TU-E-BRA-11: Volume of Interest Cone Beam CT with a Low-Z Linear Accelerator
Target: Proof-of-Concept.
AB - PURPOSE: This study demonstrates feasibility and advantages of volume of interest
(VOI) cone beam CT (CBCT) imaging performed with an x-ray beam generated from
2.35 MeV electrons incident on a carbon linear accelerator target. METHODS: The
electron beam energy was reduced to 2.35 MeV in a Varian 21EX linear accelerator
containing a 7.6 mm thick carbon x-ray target. Arbitrary imaging volumes were
defined in the planning system to produce dynamic MLC sequences capable of
tracking off-axis VOIs in phantoms. To reduce truncation artefacts, missing data
in projection images were completed using a priori DRR information from the
planning CT set. The feasibility of the approach was shown through imaging of an
anthropomorphic phantom and the head-and-neck section of a lamb. TLD800 and EBT2
radiochromic film measurements were used to compare the VOI dose distributions
with those for full-field techniques. CNR was measured for VOIs ranging from 4 to
15 cm diameter. RESULTS: The 2.35 MV/Carbon beam provides favorable CNR
characteristics, although marked boundary and cupping artefacts arise due to
truncation of projection data. These artefacts are largely eliminated using the
DRR filling technique. Imaging dose was reduced by 5-10% and 75% inside and
outside of the VOI, respectively, compared to full-field imaging for a cranial
VOI. For the 2.35 MV/Carbon beam, CNR was shown to be approximately invariant
with VOI dimension for bone and lung objects. This indicates that the advantage
of the VOI approach with the low-Z target beam is substantial imaging dose
reduction, not improvement of image quality. CONCLUSIONS: VOI CBCT using a 2.35
MV/Carbon beam is a feasible technique whereby a chosen imaging volume can be
defined in the planning system and tracked during acquisition. The novel x-ray
beam affords good CNR characteristics while imaging dose is localized to the
chosen VOI. Funding for this project has been received from Varian Medical,
Incorporated.
PMID- 28518659
TI - TU-C-218-01: Effective Medical Imaging Physics Education.
AB - : A practical and applied knowledge of physics and the associated technology is
required for the clinically effective and safe use of the various medical imaging
modalities. This is needed by all involved in the imaging process, including
radiologists, especially residents in training, technologists, and physicists who
provide consultation on optimum and safe procedures and as educators for the
other imaging professionals. This area of education is undergoing considerable
change and evolution for three reasons: 1. Increasing capabilities and complexity
of medical imaging technology and procedures, 2.Expanding scope and availability
of educational resources, especially on the internet, and 3. A significant
increase in our knowledge of the mental learning process and the design of
learning activities to optimize effectiveness and efficiency, especially for
clinically applied physics. This course will address those three issues by
providing guidance on establishing appropriate clinically focused learning
outcomes, a review of the brain function for enhancing clinically applied
physics, and the design and delivery of effective learning activities beginning
with the classroom and continuing through learning physics during the clinical
practice of radiology. Characteristics of each type of learning activity will be
considered with respect to effectiveness and efficiency in achieving appropriate
learning outcomes. A variety of available resources will be identified and
demonstrated for use in the different phases of learning process. A major focus
is on enhancing the role of the medical physicist in clinical radiology both as a
resource and educator with contemporary technology being the tool, but not the
teacher. LEARNING OBJECTIVES: 1. Develop physics learning objectives that will
support effective and safe medical imaging procedures. 2. Understand specific
brain functions that are involved in learning and applying physics. 3. Describe
the characteristics and development of mental knowledge structures for applied
clinical physics. 4. List the established levels of learning and associate each
with specific functions that can be performed. 5. Analyze the different types of
learning activities (classroom, individual study, clinical, etc.) with respect to
effectiveness and efficiency. 6. Design and Provide a comprehensive physics
education program with each activity optimized with respect to outcomes and
available resources.
PMID- 28518660
TI - TU-E-217BCD-10: Dose Reduction in Digital Breast Tomosynthesis with the Dose
Reduction Prior Image Constrained Compressed Sensing (DR-PICCS) Algorithm.
AB - PURPOSE: To reduce image noise and radiation dose in Digital Breast Tomosynthesis
(DBT) reconstructions. METHODS: A retrospective study was performed on clinical
data sets acquired at a normal dose with Hologic Selenia Dimensions DBT systems.
The Prior Image Constrained Compressed Sensing (PICCS) algorithm was used to
reduce image noise. In addition, a prospective study was performed on an American
College of Radiology breast phantom at various dose levels and the PICCS
algorithm was used to reconstruct images at the corresponding radiation dose
levels. The reconstructed images were inspected visually, and the noise levels in
various regions of interest were quantitatively measured and compared between
images. RESULTS: In the case of the clinical data, the PICCS reconstructions
showed dramatic noise reduction (over 35%) with no loss of diagnostically
important features such as calcifications or low contrast lesions; visibility of
low contrast lesions was improved with PICCS. Dose reduction of 28% was possible
with the phantom data, and the low dose PICCS reconstructions of phantom data
show improved low contrast lesion detectability and lower noise. CONCLUSIONS: The
work indicates potential dose savings in digital breast tomosynthesis. The
diagnostic quality of the phantom reconstructions at 28% reduced dose was
equivalent to or better than those acquired at full dose. The noise suppression
in the clinical data sets improved visibility of low contrast lesions without
sacrificing important diagnostic features. Support for this project was provided
by a grant from Hologic Inc.
PMID- 28518661
TI - TU-E-BRB-04: Adaptive Stereotactic-Body Radiation Therapy (SBRT) Planning for
Lung Cancer.
AB - PURPOSE: Tumor shrinkage during lung SBRT has been reported. Adaptive SBRT
planning can potentially escalate dose to the target and mitigate dose to
surrounding tissues. In this study, we investigated dosimetric effects of
adaptive lung SBRT planning using cone-bean CT (CBCT) images. METHODS: 48
patients who had SBRT treatments for lung cancer in our institution were included
in this study. All patients underwent a 3D helical CT scan and 4DCT scan for
treatment planning. Treatments were delivered on Linac machines equipped with kV
OBI, CBCT, and MV EPID. CBCT images of all patients were retrospectively analyzed
to determine tumor size changes. 10 patients with the largest percentages of
tumor shrinkage were selected for adaptive planning. Plans were created on CBCT
images of each fraction using the same planning parameters as the original CT
based plans. ITV was contoured on CBCT. PTV was generated by adding 5 mm margin
to ITV. Two accumulative dose plans, non-adaptive (P-NON) and adaptive (P-ADP),
were determined for each patient using deformable image registration via Velocity
AI. Dosimetric comparisons between PNON and PADP were performed for all OARs
using RTOG0915 metrics. Statistical significances were tested using paired t-test
with a significance level of 0.05. RESULTS: Comformality ranged from 1.03 to
1.41, with small intra-subject variations (ranged from 0.01 to 0.06). Compared to
PNON, PADP reduced all dosimetric metrics and significantly in the following (p
value range: 0.02-0.04): V20Gy of lungs; D0.35cc, D1.2cc and maximum dose of
cord, D5cc and maximum dose of esophagus, D30cc of chest wall, and D15cc of
heart. Coverage to original GTV is comparable in two plans. CONCLUSIONS: Adaptive
SBRT planning for selected patients resulted in significant dose reduction for
adjacent OARs. It has the potential to further escalate dose to the target and
mitigate dose to surrounding tissues.
PMID- 28518662
TI - TU-G-BRCD-01: Will the High Cost of Proton Therapy Facilities Limit the
Availability of Proton Therapy Treatment?
AB - : The potential dose distribution advantages associated with proton therapy, and
particularly with pencil beam scanning (PBS) techniques, have lead to
considerable interest in this modality in recent years. However, the large
capital expenditure necessary for such a project requires careful financial
consideration and business planning. The complexity of the beam delivery systems
impacts the capital expenditure and the PBS only systems presently being
advocated can reduce these costs. Also several manufacturers are considering "one
room" facilities as less expensive alternatives to multi-room facilities. This
presentation includes a brief introduction to beam delivery options (passive
scattering, uniform and modulated scanning) and some of the new technologies
proposed for providing less expensive proton therapy systems. Based on current
experience, data on proton therapy center start-up costs, running costs and the
financial challenges associated with making this highly conformal therapy more
widely available will be discussed. Issues associated with proton therapy
implementation that are key to project success include strong project management,
vendor cooperation and collaboration, staff recruitment and training. Time
management during facility start up is a major concern, particularly in multi
room systems, where time must be shared between continuing vendor system
validation, verification and acceptance testing, and user commissioning and
patient treatments. The challenges associated with facility operation during this
period and beyond are discussed, focusing on how standardization of process,
downtime and smart scheduling can influence operational efficiency. LEARNING
OBJECTIVES: 1. To understand the available choices for proton therapy facilities,
the different beam delivery systems and the financial implications associated
with these choices. 2. To understand the key elements necessary for successfully
implementing a proton therapy program. 3. To understand the challenges associated
with on-going facility management to achieve an efficient fully operational
system.
PMID- 28518663
TI - TU-E-BRA-04: Real-Time Automatic Fiducial Marker Detection in Low Contrast Cine
MV Images.
AB - PURPOSE: Intrafraction motion tracking using beam-line MV images have gained much
attention because no additional imaging dose is introduced. Since MV images have
much lower contrast than kV images, a robust marker detection algorithm is a pre
requisite. In this work, we develop a novel, fast, and robust method to detect
implanted markers in low-contrast cine-MV patient images. METHODS: Several marker
detection methods have been proposed in the recent years. These methods are all
based on template matching or its derivatives. Template matching needs to match
object shape that changes significantly for different implantation and projection
angle. While these methods require a large number of templates to cover the
different situations, they are often forced to use a smaller number of templates
to reduce the computation load because their methods all require exhaustive
search in the ROI. We solve this problem by synergetic use of modern but well
tested computer vision and AI techniques - detect implanted markers utilizing
discriminant analysis for initialization and mean-shift feature space analysis
for sequential tracking. This novel approach avoids exhaustive search by
exploiting the temporal correlation between consecutive frames and makes it
possible to perform more sophisticated detection at the beginning to improve the
accuracy, followed by ultrafast sequential tracking after the initialization. The
method was evaluated using 1149 cine-MV images from 2 prostate IMRT patients and
compared with manual marker detection results from 6 researchers. The average of
the manual detection results is considered as the ground truth. RESULTS: The
average RMS errors of the automatic tracking from the ground truth are 1.9 and
2.1 pixels for the 2 patients (0.26mm/pixel). The standard deviations of the
results from the 6 researchers are 2.3 and 2.6 pixels. CONCLUSION: The proposed
method can achieve similar marker detection accuracy to manual detection in low
contract cine-MV images.
PMID- 28518665
TI - TU-E-211-01: Establishing Multidisciplinary Collaboration as a Medical Physicist.
AB - : Many medical physicists are scientists at heart and their career fulfillment
includes a balance of clinical service and research development.
Multidisciplinary collaboration is a great way for the medical physicists to
advance science and technology of our fields and the fields of our collaborators.
Cross-pollination among scientists of different fields has been the key for some
of the most significant breakthroughs in science and medicine and produced some
of the most rewarding experiences for the individuals involved. However, medical
physicists face unique challenges in establishing multidisciplinary collaboration
because our time and resources for research are often quite limited compared to
basic scientists. Yet we medical physicists are uniquely positioned and have a
tremendous opportunity to create/contribute to multidisciplinary research: our
fields are already multidisciplinary in nature and hospital environment is
problem rich. How do we establish and carry out research collaboration with
scientists of other fields? How to balance research with your higher priority
clinical service? How do you find the right multidisciplinary collaboration in
your own environment? We will discuss the challenges, provide real exemplary
solutions to the above questions, and offer advise to medical physicists who are
interested in starting or improving their multidisciplinary collaboration. There
are different kinds of multidisciplinary collaborations a medical physicist can
create and participate at different involvement levels. Multidisciplinary
collaboration is not for every medical physicist but for those who seek and
devote time to it, the experience can be truly rewarding and the impact can be
enormous. LEARNING OBJECTIVES: 1. Learn the types of multidisciplinary
collaboration medical physicists can created/participated 2. Learn the approaches
and strategies to develop collaborations with scientists and professional of
other fields3. Understand the challenges and different approaches to balance
clinical service and multidisciplinary research collaboration.
PMID- 28518664
TI - TU-E-217BCD-03: Characterization of Anatomical Noise in Mammography,
Tomosynthesis and Breast CT.
AB - PURPOSE: The role of breast density in cancer detection has been well
characterized, and newer modalities such as breast tomosynthesis and breast CT
(bCT) were developed to improve cancer detection in the dense breast by reducing
anatomical complexity. Anatomical noise was characterized on a small cohort of
patient images and compared across digital mammography, tomosynthesis, and bCT
images. METHODS AND MATERIALS: An IRB-approved and HIPPA-compliant clinical study
was performed on women undergoing breast biopsy, and mammography, tomosynthesis,
and bCT were performed on both breasts immediately prior to biopsy. A total of 23
women participated in this study, and the unaffected breast (no lesion) was
evaluated. A total of 1000 regions of interest were sampled on each image data
set, and the 2D noise power spectrum (NPS) was evaluated. This was radially
averaged to produce a 1D NPS, and the NPS was fit to a power law: ln{NPS(f)} =
alpha+betaxln(f), over an anatomically-relevant range of spatial frequencies. The
slope, beta, was averaged across patients and compared between modalities and
projections. RESULTS: The value of beta was determined for bCT data sets, and
they were 1.75 (0.424), 1.83 (0.352), and 1.79 (0.397), for the coronal, sagittal
and axial views, respectively. For tomosynthesis, beta was 3.06 (0.361) and 3.10
(0.315) for the CC and MLO views, respectively. For mammography, these values
were 3.17 (0.226) and 3.30 (0.236), for the CC and MLO views, respectively. The
values of beta for breast CT were significantly different than those for
tomosynthesis and mammography (p<0.001, all 12 comparisons). CONCLUSIONS: The
results of this investigation demonstrate that the anatomical complexity of the
breast, as characterized by the parameter beta, is statistically similar between
mammography and tomosynthesis, a somewhat surprising finding. The breast CT image
data, however, demonstrate a statistically-significant reduction in beta across
all projections. Funded in part by Hologic Corporation and by a grant from the
National Institute of Biomedical Imaging and Bioengineering, EB002138.
PMID- 28518666
TI - TU-F-213AB-01: Diagnostic Workforce and Manpower Survey.
AB - : Since AAPM Report No. 33 on Diagnostic Radiology Physics staffing is more than
20 years old, the Diagnostic Work and Workforce Study Subcommittee (DWWSS) of the
Professional Council was formed to conduct a new study and update the data. The
intent of the DWWSS study has two goals. First, it wanted to assess the number of
FTE diagnostic physicists needed to support the QC, acceptance tests, radiation
safety and other clinical functions for various imaging modalities, such as: CT
scanners, MRI units, angiography rooms, ultrasound units, nuclear medicine
imagers and other equipment. For example, the preliminary results indicate that
the median annual physics support for one CT scanner is 0.007 FTE or 12.6 hours
per unit. Second, the study wanted to provide an estimate of the cost of these
physics services in terms of a fraction of a dollar per patient examination
performed. For example, the cost for physics support of CT would be $0.27 for
each CT procedure. This information would be similar to the Abt study conducted
in Radiation Oncology. Radiation therapy physicists have utilized the Abt studies
to generate re-imbursement for physics services and to justify financially the
cost of their work efforts. Appropriate recognition for physics efforts in
Diagnostic Radiology has never been properly quantified nor appreciated. With all
the current and future changes occurring in healthcare, the information from the
DWWSS survey could be important to the future of diagnostic physicists. Although
diagnostic physicists are involved with many other activities such as teaching of
residents and research, information about the clinical equipment support effort
could be used to assess diagnostic physics staffing needs. The goals of the DWWSS
study and the preliminary findings will be presented. OBJECTIVE: 1. Present the
goals of the DWWSS Diagnostic Physicist Survey.2. Present potential benefits to
the AAPM members from this survey.3. Present findings from the preliminary
analysis of the survey.
PMID- 28518668
TI - TU-G-BRB-02: A New Mathematical Framework for IMRT Inverse Planning with Voxel
Dependent Optimization Parameters.
AB - PURPOSE: To establish a new mathematical framework for IMRT treatment
optimization with voxel-dependent optimization parameters. METHODS: In IMRT
inverse treatment planning, a physician seeks for a plan to deliver a prescribed
dose to the target while sparing the nearby healthy tissues. The conflict between
these objectives makes the multi-criteria optimization an appropriate tool.
Traditionally, a clinically acceptable plan can be generated by fine-tuning organ
based parameters. We establish a new mathematical framework by using voxel-based
parameters for optimization. We introduce three different Pareto surfaces, prove
the relationship between those surfaces, and compare voxel-based and organ-based
methods. We prove some new theorems providing conditions under which the Pareto
optimality is guaranteed. RESULTS: The new mathematical framework has shown that:
1) Using an increasing voxel penalty function with an increasing derivative, in
particular the popular power function, it is possible to explore the entire
Pareto surface by changing voxel-based weighting factors, which increases the
chances of getting more desirable plan. 2) The Pareto optimality is always
guaranteed by adjusting voxel-based weighting factors. 3) If the plan is
initially produced by adjusting organ-based weighting factors, it is impossible
to improve all the DVH curves at the same time by adjusting voxel-based weighting
factors. 4) A larger Pareto surface is explored by changing voxel-based weighting
factors than by changing organ-based weighting factors, possibly leading to a
plan with better trade-offs. 5) The Pareto optimality is not necessarily
guaranteed while we are adjusting the voxel reference doses, and hence, adjusting
voxel-based weighting factors is preferred in terms of preserving the Pareto
optimality. CONCLUSIONS: We have developed a mathematical framework for IMRT
optimization using voxel-based parameters. We can improve the plan quality by
adjusting voxel-based weighting factors after organ-based parameter adjustment.
This work is supported by Varian Medical Systems through a Master Research
Agreement.
PMID- 28518667
TI - TU-E-BRB-08: Dual Gated Volumetric Modulated Arc Therapy.
AB - PURPOSE: Gated Volumetric Modulated Arc Therapy (VMAT) is an emerging treatment
modality for Stereotactic Body Radiotherapy (SBRT). However, gating significantly
prolongs treatment time. In order to enhance treatment efficiency, a novel dual
gated VMAT, in which dynamic arc deliveries are executed sequentially in
alternating exhale and inhale phases, is proposed and evaluated experimentally.
METHODS: The essence of dual gated VMAT is to take advantage of the natural
pauses that occur at inspiration and exhalation by alternatively delivering the
dose at the two phases, instead of the exhale window only. The arc deliveries at
the two phases are realized by rotating gantry forward at the exhale window and
backward at the inhale in an alternative fashion. Custom XML scripts were
developed in Varian's TrueBeam STx Developer Mode to enable dual gated VMAT
delivery. RapidArc plans for a lung case were generated for both inhale and
exhale phases. The two plans were then combined into a dual gated arc by
interleaving the arc treatment nodes of the two RapidArc plans. The dual gated
plan was delivered in the development mode of TrueBeam LINAC onto a motion
phantom and the delivery was measured by using pinpoint chamber/film/diode array
(delta 4). The measured dose distribution was compared with that computed using
Eclipse AAA algorithm. The treatment delivery time was recorded and compared with
the corresponding single gated plans. RESULTS: Relative to the corresponding
single gated delivery, it was found that treatment time efficiency was improved
by 95.5% for the case studied here. Pinpoint chamber absolute dose measurement
agreed the calculation to within 0.7%. Diode chamber array measurements revealed
that 97.5% of measurement points of dual gated RapidArc delivery passed the 3%
and 3mm gamma-test criterion. CONCLUSIONS: A dual gated VMAT treatment has been
developed and implemented successfully with nearly doubled treatment delivery
efficiency.
PMID- 28518669
TI - TU-E-BRA-08: A Comprehensive Study on the Relationship between Image Quality and
Imaging Dose in Low-Dose Cone Beam CT.
AB - PURPOSE: To investigate image quality as a function of number of projections and
tube load per projection in compressive sensing (CS) based low-dose cone beam CT
(CBCT), and achieve optimal low-dose scan protocols in image guided radiation
therapy (IGRT). METHODS: We have performed CS-based CBCT reconstruction with
different combinations of number of projections (from 46 to 364) and mAs (from
0.2 to 2.4 mAs/view), which covers the whole clinically relevant range. Image
quality is assessed in each case. On this basis, optimal scan protocols are
analyzed according to various IGRT applications. RESULTS: Image quality degrades
~10% when the imaging dose decreases from 400 to 100 total mAs, further ~10% from
100 to 40 total mAs, and another ~80% below 40 total mAs. Image quality on iso
low-dose lines at 36.8, 72.6, 109.2 and 145.6 total mAs varies 17.16%, 13.69%,
11.99% and 5.74% in terms RMSE with various scanning protocols. CONCLUSIONS: 1)
In CS-based CBCT, image quality has little degradation with imaging dose> 100
total mAs. Optimal low-dose scan protocols likely fall in the range of 40-100
total mAs. 2) At a constant low-dose level, the scan protocol that with super
sparse views (projection number < 50) is the most challenging case. 3) The
optimal scan protocol is the combination of a medium number of projections and a
medium level of mAs/view. This is more evident when the dose is ~72.8 total mAs
or below, and when the ROI is a low-contrast or high-resolution object. 4) The
clinically acceptable lowest imaging dose level is task dependent. In our study,
72.8mAs is a safe dose level for visualizing low-contrast objects, while 12.2
total mAs is sufficient for detecting high-contrast objects of diameter greater
than 3 mm. This work is supported in part by NIH (1R01CA154747-01), Varian
Medical Systems through a Master Research Agreement, and the Thrasher Research
Fund.
PMID- 28518670
TI - TU-E-217BCD-07: Pilot Study on Consistency in Size Metrics for a Multimodality
PEM/MR Breast Imaging Approach.
AB - PURPOSE: In this study, we evaluated the degree of consistency between size
metrics obtained from PEM and MRI to determine the intrinsic effectiveness of a
multimodality approach using these two systems for breast imaging. METHODS: Under
an IRB-approved protocol, 42 cases were considered (16 patients with 28 lesions),
each consisting of an MRI data set and corresponding PEM data set, with an
inclusion criterion of being obtained within 2 weeks of each other. Lesions were
delineated manually on the PEM images and semi-automatically on the MRI images
for efficiency. In addition to volume, equivalent sphere diameter (ESD) was
evaluated for each lesion. This metric describes the diameter of a sphere with
the same volume as that of the lesion, and is useful for minimizing the cubic
impact of a single voxel contribution inherent to volume calculations. RESULTS:
The relationship between PEM based volumes and MRI based volumes showed a linear
trend around VolMRI=VolPEM demonstrating a degree of consistency in the two
volumes. The correlation between VolMRI and VolPEM was calculated as 0.547 with a
corresponding p-value of 0.00018 demonstrating a significant correlation. The
associated concordance was calculated as 0.534. The ESD metric showed a more
significant linear trend with correlation 0.733 and corresponding p-value 3.5*10
8, indicating consistency in lesion size. The concordance is 0.717, indicating
high reproducibility. CONCLUSION: Multimodality PEM/MRI breast imaging has the
potential to combine functional and molecular imaging information for a powerful
tool in cancer staging and evaluation of response to therapy. The resulting,
expanded data set is of use only if fundamental size metrics are consistent
between the two modalities. Our pilot data demonstrates that size metrics as we
extracted from the image data are consistent between PEM and MRI breast image
sets.Maryellen Giger is a stockholder in R2 Technology/Hologic, has equity in
Quantitative Insights, and receives royalties from Hologic, GE Medical Systems,
MEDIAN Technologies, Riverain Medical, Mitsubishi and Toshiba. It is the
University of Chicago Conflict of Interest Policy that investigators disclose
publicly actual or potential significant financial interest that would reasonably
appear to be directly and significantly affected by the research activities.
PMID- 28518671
TI - TU-E-BRA-10: Personalized Utility Function for Radiotherapy Based on Pulmonary
Ventilation of Locally Advanced Lung Cancer Patients.
AB - PURPOSE: To develop tailor-made utility functions based on each patient's
pulmonary function distribution so that personalized organ-function-based
treatment plan is obtained for locally advanced lung cancer patients. METHODS:
Five locally advanced lung cancer patients were retrospectively evaluated in the
study. Fractional regional ventilation was obtained by performing subtraction of
spatially matched and corrected 4DCT images. Histogram of the fraction
ventilation values was generated for each patient. The cumulative distribution
function (CDF), which represented an inverse relationship with the desired dose
to each voxel for function preservation, showed potential as personalized utility
function. In order to spare the majority of the volume with pulmonary function, a
more aggressive utility function was defined as a piece-wise linear function
based on the most frequent fractional ventilation value (peak of the histogram).
This utility function was used in the objective function during treatment
planning. Conventional objectives and constraints were maintained during the
planning process. RESULTS: Both conventional plan and personalized functional
plan were classified as satisfactory plans by physician based on conventional
dose and dose-volume metrics. However, functional plan successfully spared high
ventilation volume based on each patient's unique condition. When spatial
function information was included to collect function dose/dose-volume metrics,
significant reduction of fV20, fV30 and mean lung dose was achieved by function
based personalized plan with p-value < 0.01. CONCLUSIONS: Organ-function-based
radiotherapy has been presented to incorporate patient's pulmonary function in
hopes of reducing the risk of complications. Current methods utilize the function
information in the same fashion across patients. We took one step further to not
only incorporate heterogeneous pulmonary function during treatment planning but
also generate personalized utility function based on the function distribution of
each patient. AAPM Research Seed Funding Initiative.
PMID- 28518672
TI - TU-C-217A-01: The Joint Commission Sentinel Event Alert 47 - Impact and
Experience.
AB - On August 24, 2011 The Joint Commission (TJC) issued Sentinel Event Alert #47:
Radiation Risks of Diagnostic Imaging. This document goes far beyond traditional
state compliance and is based on sound concepts issued by FDA in 2010. It
explores numerous means by which facilities can avoid patient harm from imaging
procedures. TJC and state inspectors have begun to ask facilities how they have
addressed these concerns. This presentation will explore the Sentinel Event Alert
#47 document, and summarize the results of Audits performed to assess progress
and identify areas for improvement.
PMID- 28518673
TI - TU-E-217BCD-09: The Feasibility of the Dual-Dictionary Method for Breast Computed
Tomography Based on Photon-Counting Detectors.
AB - PURPOSE: To investigate the feasibility of an Iterative Reconstruction (IR)
method utilizing the algebraic reconstruction technique coupled with dual
dictionary learning for the application of dedicated breast computed tomography
(CT) based on a photon-counting detector. METHODS: Postmortem breast samples were
scanned in an experimental fan beam CT system based on a Cadmium-Zinc-Telluride
(CZT) photon-counting detector. Images were reconstructed from various numbers of
projections with both IR and Filtered-Back-Projection (FBP) methods. Contrast-to
Noise Ratio (CNR) between the glandular and adipose tissue of postmortem breast
samples were calculated to evaluate the quality of images reconstructed from IR
and FBP. In addition to CNR, the spatial resolution was also used as a metric to
evaluate the quality of images reconstructed from the two methods. This is
further studied with a high-resolution phantom consisting of a 14 cm diameter, 10
cm length polymethylmethacrylate (PMMA) cylinder. A 5 cm diameter coaxial volume
of Interest insert that contains fine Aluminum wires of various diameters was
used to determine spatial resolution. RESULTS: The spatial resolution and CNR
were better when identical sinograms were reconstructed in IR as compared to FBP.
In comparison with FBP reconstruction, a similar CNR was achieved using IR method
with up to a factor of 5 fewer projections. CONCLUSIONS: The results of this
study suggest that IR method can significantly reduce the required number of
projections for a CT reconstruction compared to FBP method to achieve an
equivalent CNR. Therefore, the scanning time of a CZT-based CT system using the
IR method can potentially be reduced.
PMID- 28518674
TI - TU-E-BRB-03: Biological Dose Optimization for SBRT of Lung Cancer: One Size Does
Not Fit All.
AB - PURPOSE: Given the differences in tumor size and location, encountered in lung
SBRT, we hypothesize that 'one dose fractionation regimen does not fit all', i.e.
that there is a role for patient-specific dose prescription based on optimization
of biological models. METHODS: Sixty one NSCLC patients (tumor volume 46.5+/-47.3
cc) treated with stereotactic body radiotherapy (48 Gy in 4fx) were
retrospectively studied. Clinically treated plans were generated using Brainlab's
Pencil Beam (PB-BL), and then recalculated with fixed MUs using Anisotropic
Analytic Algorithm (AAA), Pencil Beam (PB-EC), Monte Carlo (MC) and Collapsed
Cone-Convolution (CCC). DVHs were exported to calculate TCP (Poisson) and NTCP
(Lyman-Kutcher-Burman). TCP/NTCP model parameters were utilized from published
data. For each dose distribution two dose response curves were generated by
scaling the prescription dose and assuming a linear relationship between the
prescription dose and entire 3D dose distribution. In addition, associations were
assessed between changes in each algorithm's TCP relative to PB-BL, target
diameter, and local density (density of the 70% isodose covering the PTV).
RESULTS: For PB-BL, mean TCP was 99.6%+/-0.9%, whereas for same MUs, mean TCP for
PB-EC, AAA, CC and MC plans were 96.5+/-14.3%, 74.6+/-31.6%, 74.4+/-32.4% and
76.8+/-32.0%, respectively. With the same prescription dose for all plans, TCP
values changed to 98.1+/-8.7%, 96.5+/-15.3%, 77.5+/-28.6%, 85.4+/-25.8% and
92.9+/-20.1% for PB-BL, PB-EC, AAA, and CCC, MC, respectively, indicating that
AAA and CCC dose distributions are likely less homogeneous relative to MC. The
TCP improvement was 12.3%, 8.9% and 4.4% for AAA, CCC and MC-based plans when the
average NTCP before optimization was set as the upper limit for lung toxicity.
CONCLUSIONS: This work supports patient-specific dose prescription strategies,
based on biological optimization, for lung SBRT. However, further investigation
is warranted. Acknowledgement: supported in part by a grant from Varian Medical
Systems.
PMID- 28518675
TI - TU-E-BRA-03: Real-Time Fiducial Detection and Prostate Movement Assessment with
Cine MV Images in RapidArc Treatments.
AB - PURPOSE: To develop an algorithm for detection of metallic fiducial markers in
cine MV images, and to assess the prostate movement during RapidArc treatment.
METHODS: A Varian TrueBeam linear accelerator (LINAC) was used to deliver
RapidArc treatment for prostate patients. Cine images were acquired with the
onboard electronic portal imaging device (EPID) using the MV therapeutic beam.
Three metallic fiducial markers were implanted inside the prostate. To detect the
fiducial position, we explicitly account for the possible marker blockage by MLC
during beam modulation. If the marker is not blocked, we employ the planning
coordinates of the marker centroids projected onto the cine MV images and perform
template matching in the vicinity of its projection to localize the actual
position of the marker. Displacements of the fiducial markers are assessed by
comparing the actual and planned positions. RESULTS: We analyzed ~280 cine MV
images acquired during a 55-sec RapidArc treatment for a prostate patient. The
three markers were visible in about 46%, 52%, and 48% of the images, and at least
one fiducial was visible during almost entire treatment (97% of the time). The
marker detection algorithm agrees well with manual detection (< 0.2 mm). The mean
displacement for each fiducial was 0.40 +/- 0.42, 0.27 +/- 0.29, and 0.46 +/-
0.34 mm. The maximum displacement was 2.33, 1.75, and 2.23 mm. CONCLUSIONS: An
algorithm for automatic detection of fiducial markers in cine MV images has been
developed. The prostate movement during a RapidArc treatment has been analyzed
for a patient with implanted markers. Accurate target positioning is achieved at
all times during treatment. In light of the random nature of intrafraction
prostate motion, this work represents an important step toward real-time image
guided prostate radiation therapy.
PMID- 28518676
TI - TU-E-217BCD-02: An X-Ray Scatter Correction Method for Dedicated Breast Computed
Tomography.
AB - PURPOSE: To reduce the impact of x-ray scatter in dedicated breast computed
tomography (BCT) images. METHODS: The inclusion of x-ray scatter in BCT
projections results in cupping artifacts, loss of contrast, and quantitative
inaccuracies. To correct for this, an additional set of BCT projections is
acquired with a tungsten plate placed between the x-ray source and the patient
breast. The tungsten plate includes a two-dimensional grid of perforations to
generate an array of pencil beams. Due to the limited area illuminated by the x
ray pencil beams, an array of signals of primary x-rays only is obtained. At the
pencil beam locations, the difference between the plate projections and the
standard projections is an estimate of the scatter present in the latter. These
estimates are interpolated to obtain scatter-only estimates of the whole images,
which are subtracted from the standard projections, resulting in BCT projections
with primary signal only, which are then reconstructed. To reduce the impact of
the quantum noise of the scatter signal, the resulting reconstructions are noise
filtered. Monte Carlo simulations were performed to estimate the amount of
scatter included in the pencil beams and the dose from these additional
projections. The algorithm was tested using breast phantoms on a BCT clinical
prototype system. RESULTS: The maximum scatter signal in the pencil beams is 2.2%
(mean of 0.7%) of the total signal, so the pencil beams are an excellent estimate
of the primary-only signal. The additional projections Result in only 0.4% of the
glandular dose of the standard projections. The homogeneity of the resulting
phantom images, the signal difference between adipose and glandular tissue,
reconstruction accuracy, and contrast-to-noise ratios were improved with this
algorithm. CONCLUSIONS: The proposed algorithm has the potential to substantially
improve BCT image quality with practically no additional dose to the patient
breast.
PMID- 28518677
TI - TU-D-217A-01: CTDI and Patient Dose: A European Perspective.
AB - : Dose in CT has been a dominant topic in Medical Physics for at least a decade.
This was for good reason since increasing use of CT necessarily led to an
increase of cumulative dose to the population and inappropriate use of CT in some
cases led to an unnecessarily high exposure of patients with subsequent coverage
in the U.S. media. Fortunately, this situation also triggered a number of
positive technical developments and fruitful initiatives worldwide. Currently,
even "sub-mSv CT" is a realistic topic. However, we also engage in extensive
discussions of the topic "CTDI and patient dose". They do not always seem to be
pragmatic and sometimes are unnecessarily complicated. One reason may be that the
topics computed tomography dose index (CTDI) and patient dose are seen
necessarily combined. This lecture aims at discussing and hopefully helping to
resolve some of the issues. Key points and suggestions are the following: * CTDI
is a proven and reasonably good concept for scanner dosimetry and quality control
(QC) on standard 64-row scanners. There is no major debate on CTDI efficiency and
similar issues in Europe. * The new IEC scanner dosimetry concept to be used for
wider detectors is acceptable; there is no need for new and heavy phantoms. *
There still is a need of phantoms and concepts for QC of automated exposure
control systems in CT. * CTDI should not and need not be changed and expanded to
assess patient dose. * Patient dose estimates (both organ and effective dose) are
based on air kerma measurements (without a CTDI phantom) and MC calculations
using mathematical phantoms and/or voxel models. The DLP-to-E conversion which is
accepted in Europe for more than a decade was based on this approach. * Patient
dose estimates, both organ and effective dose, should be scanner- and patient
specific. Fast MC programs and dose software allow for this. Manufacturer
cooperation is a necessity, and there are first positive examples. * The concept
of diagnostic reference levels (DRL) which was started in Europe in the 1990s and
is in wide use today has to be revisited. It need not be based on CTDI further on
but, for example, on a revised scanner- and patient-specific DLP-to-E conversion.
* An international consensus on the topics CTDI and patient dose appears
desirable. All these points do not mean a revolution but rather aim at staying
with established equipment. The two major objectives are to * avoid unnecessary
QC burden of medical physicists who are threatened with extended CTDI
measurements * provide more reliable and understandable information regarding
patient dose in real time. Organ dose and effective dose are preferable to DLP.
LEARNING OBJECTIVES: 1. Understand that CTDI is a technical concept for scanner
acceptance and constancy testing 2. Learn about concepts for patient- and scanner
specific patient dose estimates 3. Learn about the concept of diagnostic
reference levels and its strengths and weaknesses Research sponsored by Siemens
Healthcare and by CT Imaging GmbH, both in Erlangen, Germany.
PMID- 28518678
TI - TU-E-218-01: PET/CT QA/QC and Acceptance Testing.
AB - : Combined PET/CT imaging has become a routine imaging technique in diagnostic
radiology and nuclear medicine alike. In this regard a thorough understanding of
this modality's quality assurance and control procedures including acceptance
testing is a necessary pre-requisite to ensure the optimal performance of this
imaging modality. This session is designed to explain the QA and QC procedures
for a PET/CT scanner with examples from two different manufacturers. The session
will also cover the frequency of these tests and the elements to implement a
QA/QC program for PET/CT imaging. Finally the session will cover the NEMA
standard for acceptance testing of PET scanners and their meanings as well as
additional recommended tests for hybrid (PET/CT) systems. LEARNING OBJECTIVES: 1.
Summarize the signal processing steps for coincidence detection 2. Understand the
components of a daily QA procedure 3. Identify and trouble shoot possible sources
of failure in daily QA 4. List the recommended frequency of QA/QC tests 5.
Describe the process of scanner calibration 6. Name the different components of
the NEMA test used for PET acceptance testing 7. Understand the meaning of the
results of the NEMA tests.
PMID- 28518679
TI - TU-E-BRB-07: An EPID Based Dosimetric Verification Tool for SBRT with High Dose
Rate FFF Beams.
AB - PURPOSE: The increasing use of unflattened high dose rate and/or small sized
fields in stereotactic body radiosurgery (SBRT) presents a significant challenge
and calls for new tools for dosimetric measurements and quality assurance (QA).
The purpose of this work is to investigate a high spatial resolution (0.2mm) and
high frame rate (50Hz) amorphous silicon flat-panel electronic portal imaging
device (EPID) from Perkin Elmer for SBRT. METHODS: A Monte Carlo N-Particle
eXtended (MCNPX) simulation and convolution based calibration procedure has been
developed to derive a voxel-based response function specific to the EPID
construct and beam characteristics. Both standard photon beams and flattening
filter free (FFF) beams of all energies from Varian TrueBeam STX were studied and
the linearity and dose rate dependence were tested. EPID with detailed materials
composition was simulated using the MCNPX to generate a scatter kernel composed
of dose deposition in the EPID phosphor, and optical photon spreading and to
deconvolve the EPID images to high spatial resolution photon fluence map. The
fluence map was convolved with MCNPX generated kernels to the 3D dose
distribution in the phantom and compared with pinpoint ion chamber and film
measurements. RESULTS: EPID response showed excellent linearity (R2>0.9998) and
dose rate dependence less than 1.8% for up to 2400MU/min. Output factors for
field sizes ranging from 1*1 to 20*20cm2 were measured and used to fit the
optical photon glare kernel. Fluence profiles deconvolved using MCNPX scattering
kernel agrees with the measurements to within 2%. Results of typical pre
treatment QA test exhibit excellent spatial resolution required for SBRT.
CONCLUSIONS: The high spatial resolution and high frame rate EPID proved to be an
accurate and efficient tool for SBRT QA. Through convolution with MCNPX
scattering core and comprehensive EPID calibration, accurate 3D dose maps can be
generated for independent dosimetric verification of SBRT treatments.
PMID- 28518680
TI - TU-G-BRB-01: Continuous Path Optimization for Non-Coplanar Variant SAD IMRT
Delivery Using C-Arm Machines.
AB - PURPOSE: To develop and investigate a continuous path optimization methodology to
traverse prescribed non-coplanar IMRT beams with variant SADs, by orchestrating
the couch and gantry movement with zero-collision, minimal patient motion
consequence and machine travel time. METHODS: We convert the given collision zone
definition and the prescribed beam location/angles to a tumor-centric coordinate,
and represent the traversing path as a continuous open curve. We proceed to
optimize a composite objective function consisting of (1) a strong attraction
energy to ensure all prescribed beams are en-route, (2) a penalty for patient
motion inducing couch motion, and (3) a penalty for travel-time inducing overall
path-length. Feasibility manifold is defined as complement to collision zone and
the optimization is performed with a level set representation evolved with
variational flows. The proposed method has been implemented and tested on
clinically derived data. In the absence of any existing solutions for the same
problem, we validate by: (1) visual inspecting the generated path rendered in the
3D tumor-centric coordinates, and (2) comparing with a traveling-salesman (TSP)
solution obtained from relaxing the variant SADs and continuous collision
avoidance requirement. RESULTS: The proposed method has generated delivery paths
that are smooth and intuitively appealing. Under relaxed settings, our results
outperform the generic TSP solutions and agree with specially tuned versions.
CONCLUSIONS: We have proposed a novel systematic approach that automatically
determines the continuous path to cover non-coplanar, varying SAD IMRT beams. The
proposed approach accommodates patient-specific collision zone definition and
ensures its avoidance continuously. The differential penalty to couch and gantry
motions allows customizable tradeoff between patient geometry stability and
delivery efficiency. This development paves the path to achieve safe, accurate
and efficient non-coplanar IMRT delivery with the advanced robotic controls in
new-generation C-arm systems, enabling practical harvesting of the dose benefit
offered by non-coplanar, variant SAD IMRT treatment.
PMID- 28518681
TI - TU-E-BRA-07: Post-Operative Eye Plaque Imaging Using Tomotherapy MVCT.
AB - PURPOSE: Intra-operative ultrasound is used to verify the positioning of
episcleral eye plaques used to treat ocular melanoma. Ultrasound can be ambiguous
because of image artifacts, and plaques may shift position after surgery.
Ultrasound verification is particularly challenging for anterior tumors. Post
operative imaging could be used to trigger interventions that would prevent local
treatment failure. We investigated if, and under what conditions, the Tomotherapy
megavoltage computed tomography (MVCT) system could be used to perform post
implantation verification of eye plaque positioning. METHODS: Plaques were placed
on a preserved cow's eye, and imaged with the megavoltage CT of a Tomotherapy
linear accelerator (Accuray, Sunnyvale, CA). The images were visually and
quantitatively assessed to determine if they were of sufficient quality to verify
tumor coverage and plaque tilt with respect to the sclera. We used the visibility
of the lens as a proxy for visibility of a tumor. To test the utility of
hypothetical higher beam current Tomotherapy images, we averaged sequential
images of the same setup. RESULTS: The plaque, the lens of the eye, and the globe
are visible in the images. The CNR of the lens with respect to the vitreous was
5.6 for a single image. For 10 images averaged, the CNR was 9.2. Estimated dose
from a single image was 1.3 cGy (body CTDIvol); even 10 times this dose would be
an acceptable image-guidance dose for radiotherapy patients. One limitation of
the imaging procedure is the long scan time (up to 240 seconds), during which
time any significant patient motion would lead to image artifacts. Human trials
on eye plaque patients are planned. CONCLUSIONS: Tomotherapy MVCT imaging could
be used to verify tumor coverage and plaque tilt after episcleral plaque
implantation. Tumors should be visible in standard Tomotherapy images but higher
beam current images would be preferred if available.
PMID- 28518682
TI - TU-E-217BCD-06: Cone Beam Breast CT with a High Resolution Flat Panel Detector
Improvement of Calcification Visibility.
AB - PURPOSE: To investigate the advantage of a high resolution flat panel detector
for improving the visibility of microcalcifications (MCs) in cone beam breast CT
Methods: A paraffin cylinder was used to simulate a 100% adipose breast. Calcium
carbonate grains, ranging from 125-140 MUm to 224 - 250 MUm in size, were used to
simulate the MCs. Groups of 25 same size MCs were embedded at the phantom center.
The phantom was scanned with a bench-top CBCT system at various exposure levels.
A 75MUm pitch flat panel detector (Dexela 2923, Perkin Elmer) with 500MUm thick
CsI scintillator plate was used as the high resolution detector. A 194 MUm pitch
detector (Paxscan 4030CB, Varian Medical Systems) was used for reference. 300
projection images were acquired over 360 degrees and reconstructed. The images
were reviewed by 6 readers. The MC visibility was quantified as the fraction of
visible MCs and averaged for comparison. The visibility was plotted as a function
of the estimated dose level for various MC sizes and detectors. The MTFs and DQEs
were measured and compared. RESULTS: For imaging small (200 MUm and smaller) MCs,
the visibility achieved with the 75MUm pitch detector was found to be
significantly higher than those achieved with the 194MUm pitch detector. For
imaging larger MCs, there was little advantage in using the 75MUm pitch detector.
Using the 75MUm pitch detector, MCs as small as 180 MUm could be imaged to
achieve a visibility of 78% with an isocenter tissue dose of ~20 mGys versus 62%
achieved with the 194 MUm pitch detector at the same dose level. CONCLUSIONS: It
was found that a high pitch flat panel detector had the advantages of extending
its imaging capability to higher frequencies thus helping improve the visibility
when used to image small MCs. This work was supported in part by grants CA104759,
CA13852 and CA124585 from NIH-NCI, a grant EB00117 from NIH-NIBIB, and a
subcontract from NIST-ATP.
PMID- 28518683
TI - TU-E-BRCD-01: The Emerging Role of Image-Guidance for Breast Radiotherapy.
AB - : Breast radiotherapy has undergone significant innovation in the past 10 years
and the frequency of image-guided radiation therapy (IGRT) is increasing. This
session will review clinical indications for breast radiotherapy (RT) and
conventional RT methods. Ongoing clinical innovations in breast RT techniques
will then be highlighted (e.g., partial breast irradiation, IMRT and VMAT for
irradiation of the internal mammary chain). Finally, the emerging role of IGRT
will be discussed with its application to improving setup reproducibility and
designing appropriate target margins. The IGRT methods will include surface
imaging although the focus will remain on more widely-available IGRT systems such
as CBCT and kV imaging. a.Brief clinical review of RT as a function of breast
cancer stage according to RTOG guidelines b.Dosimetric advances in breast RT,
including IMRT and VMAT for nodal irradiation and partial breast irradiation for
early-stage cancer c.The role of IGRT for setup reproducibility and margin design
d. IGRT for adaptive RT in cases of seroma reduction. LEARNING OBJECTIVES: 1.
Review the clinical targets for breast RT as a function of cancer stage 2. Learn
about innovative uses of advanced radiotherapy techniques for breast treatment 3.
Highlight the emerging role of IGRT to guide planning and treatment. Jan-Jakob
Sonke's research is sponsored by Elekta Corporation.
PMID- 28518684
TI - TU-G-211-01: New Member Symposium.
AB - As a new member of the AAPM, it's easy to feel overwhelmed by the size and
complexity of the association and to be unaware of the benefits and opportunities
available to members. At this year's AAPM national meeting in Charlotte, we will
host a New Member Symposium, where you can learn more about the organization,
member resources, opportunities to get involved, and about topics of particular
interest to new professionals. We encourage you to take advantage of this great
opportunity to learn valuable information and to grow your professional network.
Following an introduction from Dr. Gary A. Ezzell, the AAPM President; Michael
Woodward of the AAPM staff will provide a crash course on the AAPM structure and
organization, as well as some pointers on navigating the website. Next will be
Dr. Michael Mills presenting on the current state of the U.S. Medical Physics
Workforce, Staffing, Supply & Demand, and Limited Residency slots. Registered
attendees will receive a raffle ticket for entry in a drawing to win a
complimentary registration for the 2013 Annual Meeting in Indianapolis. In
addition, all new members who register for the Symposium will receive a drink
ticket good for one complimentary beer served after the New Member Symposium
during the social with committee chairs from 4 AAPM Councils: Science, Education,
Professional, and Administrative.
PMID- 28518685
TI - TU-E-217BCD-08: Extraction and Insertion of Tumor Masses in Cone Beam Breast CT
Images.
AB - PURPOSE: To develop and validate algorithms for extraction and insertion of three
dimensional (3D) profiles of tumor masses in cone beam breast CT (CBBCT) images
to create simulated abnormality for evaluation with observer performance study.
METHODS: A bench-top experimental CBBCT scanner was constructed and used to image
mastectomy breast specimens with IRB approval. 5 sets of CBBCT images with
confirmed tumor masses and 2 sets of normal CBBCT images were selected and used
for this study. All CBBCT images were first corrected for cupping artifacts. The
corrected images were then processed to reduce their noise levels and form the
denoised images. The corrected and denoised CBBCT images for normal breasts were
then segmented into adipose and glandular voxels. The images for abnormal breasts
were reviewed by mammographers with the help of clinical images and reports to
delineate the tumor masses and form 3D tumor maps. Using these maps, the 3D tumor
profiles were rescaled to average glandular signals around the insertion
locations in normal images. The boundaries of the 3D rescaled tumor profiles were
smoothed to avoid sharp edge. The resultant 3D tumor profiles were inserted onto
cupping artifact corrected normal CBBCT images by replacing the signals in
adipose voxels near the insertion locations. The cupping artifacts were then
added back to generate the simulated abnormal CBBCT images. These images were
then visually compared with actual abnormal images for their degree of realism.
RESULTS: Based on visual comparison, the simulated abnormal CBBCT images showed
no significant difference in realism from actual abnormal CBBCT images.
CONCLUSIONS: We have successfully demonstrated the technique to extract 3D tumor
profiles from abnormal CBBCT images and insert them onto normal CBBCT images to
form simulated abnormal images for use in observer performance study. This work
was supported in part by grants CA104759, CA13852 and CA124585 from the NIH-NCI,
a research grant EB00117 from the NIH-NIBIB, and a subcontract from NIST-ATP.
PMID- 28518686
TI - TU-E-BRB-02: A Decision Support Tool for SBRT Planning Using a Searchable DVH
Database.
AB - PURPOSE: Develop a decision support tool that aids dosimetrists, physicians, and
physicists in assessing and improving plan quality through comparison to plans
previously used in similar clinical situations. METHODS: Software was developed
to capture and store DVHs and other clinically relevant treatment plan
characteristics in a database. In addition to the plan DVH, the database contains
a total of 24 plan characteristics including fractionation, prescribed dose,
treatment volume, prior surgery, tumor position, and smoking history. DVH and
other plan data was captured from the treatment planning system via exported
dicom RT files. Structures in the plan were automatically matched by name to a
list of standard structures using a system of regular expressions. Additional
fields were entered manually using a simple java interface. As a support tool, a
plan under development can be quickly compared to similar plans in the database
based on selected plan characteristics. A plot displaying the current and
historical DVHs provides an easy visual comparison. Our interface also provides
statistics for comparison for each dose/volume level such as average, minimum,
maximum and standard deviation. RESULTS: DVHs from 111 lung SBRT plans treated
from 2009-2011 were imported in accordance with an approved IRB protocol. As an
example of data comparisons that can be easily performed to guide plan
evaluation, we examined plans prescribing 5400cGy in 3 fractions and found that
tumors >7.5cc (n=34) had an average PTV coverage of 94.2% (range: 73.5-95.0%),
and tumors =7.5cc (n=35) had an average PTV coverage of 94.9% (range: 81.6
99.6%). CONCLUSION: A searchable DVH database was constructed to provide
planners, physicists, and physicians with a straightforward means of comparing
plans against historic distributions of DVHs. In the future, outcome data will be
included in the database to strengthen its functionality as a decision support
and research tool.
PMID- 28518687
TI - TU-G-213AB-02: Time-Space Compression for Fun and Profit: How to Do More, in Less
Time, Without the Stress and Mess.
AB - : "Time-space compression" means "processes that ... revolutionize the objective
qualities of space and time." (David Harvey, The Condition of
Postmodernity.)Modern workflows suffer from negative time-space compression:
computers, internet, email, smartphones, texting and chat all promise
productivity, yet they can encroach on our time and clutter our minds without
eliminating those lurking piles of paper. Physicists in medicine face additional
technology-related challenges on top of all that. However, the laws governing our
time, workspaces, and teams are universal. Understand those laws, and you
understand how to control the forces that derail personal and team workflow.
Then, by drawing on a few practical techniques, you can create positive time
space compression: revolutionizing your workspace and systems to get more done,
with noticeably less stress, balancing work and fun in all your life areas,
keeping your desk so clean your associates will think you're going on vacation.
An approach called Total, Relaxed Organization (TRO) makes this possible. TRO was
developed by Priacta, Inc. (Kevin Crenshaw's company) using best practices from
many popular time management systems. TRO has measurable Results: an average net
gain of 581 productive hrs/yr, and average stress reduction of 59.6% from all
sources combined. While these numbers are subjective and self-reported, they
indicate a consistent improvement in the quality of life for TRO adherents. This
working presentation compresses a (normally paid) 7-hour TRO personal coaching
session into a 75-minute interactive, entertaining, and highly-practical workshop
for each participant. LEARNING OBJECTIVES: 1. Understand the key principles/laws
that govern your use of time and (work)space. 2. Identify your personal barriers
that currently work against those principles. 3. Create a personal action plan
(based on those time/workspace principles and practical techniques) to re
engineer your personal and team workflow for optimal results.
PMID- 28518688
TI - TU-E-BRA-02: A Method to Remove Support Arm Backscatter from EPID Images.
AB - PURPOSE: To develop a method for removing the effect of support arm backscatter
from Varian electronic portal imaging devices (EPIDs), improving the dosimetric
abilities of the imager. METHODS: A physical, kernel based model of the
backscatter signal produced during an exposure was developed. The model
parameters were determined through an optimization process, comparing measured
images without arm backscatter (EPID removed from arm) to measured images that
include arm backscatter. The backscatter model was used to develop a backscatter
correction process that removes the support arm backscatter from measured EPID
images. The correction process was tested by applying the method to measured
images of 17 rectangular asymmetric fields and comparing the Result to off-arm
images. The same process was repeated with 42 IMRT fields. RESULTS: The
backscatter removal process was able to effectively remove the arm backscatter
from all of the measured images and accurately predict the measured off-arm
images. Comparing the corrected images to the measured off-arm images, the mean
absolute difference at the centre of each rectangular field was 0.29% (standard
deviation 0.18%). This is an improvement over the uncorrected images which gave a
mean difference of 1.01% (standard deviation 0.73%). The largest discrepancy
observed with the corrected images was 0.6%, compared to 2.8% for the uncorrected
images. Comparing the corrected IMRT images to the measured off-arm images, an
overall mean gamma value of 0.28 (standard deviation 0.04) was found using 2%,
2mm criteria. Comparison of the uncorrected images to the measured off-arm images
resulted in an overall mean gamma of 0.40 (standard deviation 0.10). CONCLUSIONS:
A method for accurately and reliably removing the effect of support arm
backscatter from EPID images has been developed and extensively tested. The
method can be applied to any measured EPID image and does not require any
additional information about the exposure.
PMID- 28518689
TI - TU-E-217BCD-01: X-Ray Spectra for Breast CT.
AB - PURPOSE: To study a range of x-ray spectra with regard to their suitability for
dedicated breast CT, taking into account realistic tube loading limitations.
METHODS: A simple theoretical model was used to get a preliminary indication of
the best mono-energetic x-ray energy as a function of object size. That model was
extended to poly-energetic spectra and used to study a range of object sizes,
tube voltages, filter materials, and filter thicknesses. Spectra from IPEM Report
78 were used as input to the model. Initially we have looked at lanthanide
filters (Z = 57-60) and tube voltages from 30 to 80 kVp. Outputs from the model
included contrast, contrast-to-noise ratio (CNR), dose, dose efficiency
(CNR2/dose), and tube loading. Dose was estimated as incident minus transmitted
energy fluence. We have also started experiments to verify the computational
results. Experiments are done using a bench-top cone beam CT and a 14 cm diameter
cylindrical PMMA phantom filled with liquid mixtures equivalent to breast tissue
of varying glandularity. We use reconstructed data to determine the CNR of a test
block representing 100% glandular breast tissue, immersed in the liquid. Air
kerma measurements are obtained at the center and periphery of the phantom, and
used in the calculation of dose efficiency. Monte Carlo calculations are being
done to get a more accurate dose estimate. RESULTS: For a constant CNR,
computational results indicate that as filter thickness increases above 0.4 mm
dose efficiency plateaus. However, the power required to maintain a constant CNR
becomes prohibitively large for filter thicknesses greater than 0.3 mm.
CONCLUSIONS: Spectra generated at tube voltages above 40 kVp are likely to
provide the best trade-off between dose efficiency and tube loading. For
lanthanide filters, there is little benefit from using thicknesses greater than
0.3 mm.
PMID- 28518690
TI - TU-D-213AB-01: How You Can Be the Speaker and Communicator Everyone Wants You to
Be.
AB - Effectiveness of an oral presentation depends on the ability of the speaker to
communicate with the audience. An important part of this communication is
focusing on two to five key points and emphasizing those points during the
presentation. Every aspect of the presentation should be purposeful and directed
at facilitating learners' achievement of the objectives. This necessitates that
the speaker has carefully developed the objectives and built the presentation
around attainment of the objectives. A presentation should be designed to include
as much audience participation as possible, no matter the size of the audience.
Techniques to encourage audience participation include questioning,
brainstorming, small-group activities, role-playing, case-based examples,
directed listening, and use of an audience response system. It is first necessary
to motivate and gain attention of the learner for learning to take place. This
can be accomplished through appropriate use of humor, anecdotes, and quotations.
This course will review adult learning principles and effective presentation
skills, Learning Objectives: 1. Apply adult learning principles. 2. Demonstrate
effective presentations skills.
PMID- 28518691
TI - TU-E-217A-01: Informatics 1: DICOM and the QMP, Assessment of Color Displays.
AB - : All Medical Physicists work with the DICOM Standard every day. But the
involvement of Medical Physicists in the development of the Standard has been
limited. Recently the DICOM Standards Committee (DSC) has established a new Dicom
Working Group on Physics (i.e. WG28) and the AAPM has become the secretariat for
WG28 and a voting member of the DSC. The structure and processes involved with
making the DICOM Standard will be reviewed and the specific role DICOM WG28 has
will be summarized. LEARNING OBJECTIVES: 1. Understand the processes involved
with development of the DICOM Standard. 2. Learn how any Medical Physicist can
become involved in the process of developing the DICOM Standard 3. Learn the
charge and structure of WG28 and their current Work Items. Medical color monitors
are now widely used for Diagnostic Radiology interpretations. Business class
monitors are otherwise used for medical image presentation in clinical
departments. Both the AAPM and IEC are now developing recommendations and
standards for color monitor performance assessment in medicine. The basic
principles of color vision and metrology will be reviewed and current progress
with AAPM and IEC working groups will be summarized. LEARNING OBJECTIVES: 1.
Understand the tristimulus model for human color vision. 2. Understand the ICC
color management framework. 3. Understand the ICC color management framework. 4.
Learn how to make color measurements. 5. Learn new recommendations for color
white point specification.
PMID- 28518692
TI - TU-E-BRB-06: Best in Physics (Therapy) - Development and Experimental Validation
of EPID-Based 4D Dose Reconstruction.
AB - PURPOSE: To develop and validate an EPID-based 4D patient dose reconstruction
framework accounting for linac delivery uncertainties, interfractional and
intrafractional motions, and interplay effect. METHODS: Patients with fiducial
markers were scanned with 4D-CT for SBRT planning. Before treatment, in-room 4D
CT was performed. Both the MLC and the tumor movements were tracked by
continuously acquiring EPID images during treatment. Instead of directly using
the heterogeneous transit photon fluence measured by the EPID, this method
reconstructed the incident beam fluence based on the MLC apertures measured by
the EPID and the delivered MU recorded by the linac. To account for the time
dependent-geometry, the incident fluence distributions were sorted into their
corresponding phases based on the tumor motion pattern detected by the EPID and
accumulated as the incident fluence map for each phase. Together with 4D-CT, it
was then used for Monte Carlo dose calculation. Deformable registration was
performed to sum up the phase doses for treatment assessment. The feasibility of
using the transit EPID images for incident fluence reconstruction was evaluated
against EPID in-air measurements. The accuracy of 3D- and 4D-dose reconstruction
was validated by a motordriven cylindrical diode array for six clinical SBRT
plans. RESULTS: The average difference between the measured and reconstructed
fluence maps is within 0.16%. The reconstructed 3D-dose shows 1.4% agreement in
the CAX-dose and >98.5% gamma-passing-rate (2%/2mm) in the peripheral-dose. A
distorted dose distribution is observed in the measurement for the moving
ArcCheck-phantom. The comparison between the measured and the reconstructed 4D
dose without considering interplay fails the gammaevaluation (59%-88.9% gamma
passing-rate). In contrast, when the interplay is considered, the dose distortion
phenomena is successfully represented in the reconstructed dose (>97.6% gamma
passing-rate). CONCLUSIONS: The experimental validation demonstrates that the
proposed method provides a practical way to reconstruct the fractional 4D-doses
received by the patient and enables adaptive SBRT strategy.
PMID- 28518693
TI - TU-G-BRCD-03: Managing Patient and Organ Motion in Proton Therapy.
AB - BACKGROUND: The advent of proton based therapy has provided excitement in the
radiation oncology community. Not in the least due to the theoretically
advantageous geometrical properties of the dose deposition by such charged
particles. In this presentation I will discuss the some of the challenges, which
can make this tool sub-optimal when used in clinical practice with actual
patients. METHODOLOGY: Data and analysis on patient setup variations and organ
movement, gathered from "classical" photon therapy is projected to this new
modality. Inter and intra fractional movement will be covered as well as the
notion of margin determination in order to provide adequate coverage and in what
way this makes sense. In addition, the time frame with which these uncertainties
occur implies that different measures need to be taken and the use of in room
imaging might be needed. Further, the advent of scanning techniques again provide
an advantage as well as a disadvantage as far as movement is concerned.
CONCLUSIONS: Proton therapy is a promising technique and exciting on a clinical
and scientific level. In order to show significant improvement, knowledge with
regard to targfet determination, as well as positioning is more critical in
comparison with the classical modalities. LEARNING OBJECTIVES: 1. Knowledge on
patient and/or organ movements motion effects. 2. Categorizing the movement in
time and space. 3. Reflections on the impact of movement on proton based
treatments.
PMID- 28518694
TI - TU-E-BRA-06: Evaluation of a New MV X-Ray Detector Designed for the
TomoTherapy(r) System.
AB - PURPOSE: To evaluate the performance of a new MV X-ray detector prototype
specifically designed for use on the TomoTherapy(r) System. METHODS: A gas-filled
detector array, similar in concept to existing TomoTherapy detector arrays, has
been designed and fabricated for the TomoTherapy System. Unlike existing detector
arrays, the prototype detector array has a radius of curvature that matches the
source-to-detector distance. Also, the internal structure of the detector such as
the septa material and geometry has been optimized for MV X-rays. The prototype
detector performance was assessed by measuring the signal properties of each of
the detector channel signals. Signal, noise, and signal-to-noise ratios (SNR)
were measured. Finally, the resulting MVCT image quality was assessed. RESULTS:
The signal profile across the prototype detector more closely matches the
incident X-ray beam intensity and, in particular, is missing the characteristic
trough in the center of signal profiles from existing TomoTherapy detector
arrays. Compared to an existing detector, the mean signal is approximately equal
outside the central region. Inside the 100 central channels (out of 576 total
channels), the prototype detector signal is substantially larger than the
existing detector. The variation in the pulse-to-pulse signal (noise), after
accounting for output fluctuations, is substantially lower with the new detector.
The resulting SNR is an average of 18% higher across all channels, with an
improvement of up to 36% for the central channels. The prototype detector yielded
MVCT images that, compared to one typical system with an existing detector array,
had 7% lower image noise in the periphery and 36% lower noise at the center of
the image. CONCLUSIONS: This evaluation indicates that the performance of a new
MV X-ray detector array prototype exceeds the performance of an existing detector
array in terms of signal-to-noise ratio and resulting MVCT image quality.
PMID- 28518696
TI - TU-E-213AB-02: The Regulatory Path to Achieve QMP Requirement.
AB - : Licensure for medical physicists has been pursued for a number of years, with
success in some states and failure in others. Lessons from these cases has been
used to strengthen the licensure effort, but they have also demonstrated that
licensure may not be an option in some states. In such cases, we still need a
methodology to achieve credentialing and practice standards. A comprehensive
registration approach may provide that methodology. This talk will discuss
features of comprehensive registration, along with positive and negative aspects
of the approach. It will be demonstrated that comprehensive registration is a
viable alternative that can be used when licensure is not achievable. LEARNING
OBJECTIVES: 1. Understand the differences between licensure and the regulatory
approach. 2. Learn how the regulatory approach can achieve the goal of requiring
se of Qualified Medical Physicists with an appropriate scope of practice. 3.
Discuss ways of working with regulators to implement regulatory changes. 4.
Discuss potential draft regulatory language.
PMID- 28518695
TI - TU-E-217BCD-05: Dedicated Breast CT: Skin Thickness Measurements in a Diagnostic
Population.
AB - PURPOSE: To test the hypothesis that the mean skin thickness determined using
cone-beam dedicated breast CT varied between breasts with malignant, hyperplasia
and benign pathology, and to determine the appropriate skin thickness for Monte
Carlo based estimation of normalized glandular dose coefficients. METHODS: Breast
skin thickness was estimated in 137 women scheduled for biopsy (BI-RADS 4 or 5),
who underwent unilateral cone-beam dedicated CT of the breast to be biopsied,
after providing written informed consent and in adherence to an IRB-approved
protocol. Pathology results were available for 132 women and there were 38
malignancies. A previously reported method [Huang et al., Med Phys 35(4): 1199
206, 2008] was applied to coronal (transverse) images reconstructed to 0.273 mm
voxel size. The accuracy of the method was determined by imaging two phantoms of
differing wall thickness and shape. For each breast, the mean, intra-breast
standard deviation (SD) and the median skin thickness were computed. The mean
skin thickness and associated confidence intervals (CI) in our study population
were obtained from the mean skin thickness of each breast. RESULTS: The estimated
mean wall thicknesses for both phantoms were within +/-1% of the measured
thickness. At the 0.05 level (ANOVA), the skin thickness means did not vary
significantly with pathology (p=0.61). For each breast, the median, mean and
intra-breast SD, in mm, were in the range [0.87,2.23], [0.87,2.34], and
[0.22,0.85], respectively. From all 137 women, the mean +/- inter-breast SD and
95% CI were 1.44+/-0.25 and [1.40,1.48], respectively. CONCLUSIONS: The skin
thickness means were not different between breasts with malignant and non
malignant pathology. Our estimate of mean skin thickness is in agreement with a
previous report. Skin thickness of approximately 1.45 mm, rather than the
standard 4 mm [Wu et al., Radiology 193:83-9, 1994], is appropriate for Monte
Carlo based determination of normalized glandular dose coefficients. Supported in
part by the National Institutes of Health (NIH) grants R01 CA128906 and R21
CA134129. The contents are solely the responsibility of the authors and do not
represent the official views of the NIH or NCI.
PMID- 28518697
TI - TU-F-217A-01: Informatics 2: Dose Monitoring.
AB - : Public concern over radiation from medical imaging is now higher than ever
before and hospitals are being placed under increased scrutiny to ensure that
their patients do not receive radiation overdoses. California already requires
that there is a record of a dose estimate for every CT examination. In response,
there has been a renewed interest in research and commercial ventures for the
best method to monitor radiation dose for medical imaging procedures. The goal of
this session is to highlight some tools that are currently available for dose
monitoring, to illustrate how using these tools can improve the quality of care
at an institution, and to provide a sample of the future developments in
radiation dose monitoring. LEARNING OBJECTIVES: 1. To provide an understanding of
the basic science behind dose monitoring 2. To demonstrate few clinical
implementation of dose monitoring systems 3. To discuss the advanced concepts
currently under investigation (eg, patient size tracking) 4. To demonstrate how
dose monitoring systems can be used for improved quality initiatives.
PMID- 28518698
TI - TU-E-BRB-10: Dosimetric Consequences of Setup Errors Using CBCT for SBRT
Localization.
AB - PURPOSE: Steep dose gradients and high dose per fraction in stereotactic ablative
radiation therapy (SABR or SBRT) necessitate highly accurate tumor localization.
This study evaluates inter-fraction shifts, as defined by couch correction
analysis, and investigates the effect of tumor location and internal target
volume (ITV) on these shifts. In addition, residual errors associated with post
CBCT correction and their dosimetric consequences were quantified. METHODS: Daily
free-breathing (FB) CBCT images used for daily localization of 78 patients with
non-small cell lung cancer were retrospectively evaluated. Among the population,
39 patients also received pre-treatment kV images after CBCT alignment. ITV inter
fraction displacement was evaluated by matching the CBCT and the FB helical CT
images, and setup errors were quantified using orthogonal kV images. Associations
between ITV location and inter-fraction motion were studied by categorizing
tumors into the following locations: chest-wall seated (CWS) and island,
peripheral, central, or upper, middle and lower. Dosimetric consequences for the
patient with the largest setup error were explored. RESULTS: ITV inter-fraction
motion included the mean of the systematic error, ?inter=(-1.4, 2.0, 1.6) mm,
standard deviation (SD) of the systematic error, Sigmainter=(2.1, 4.2, 2.9) mm,
and SD of random errors, sinter=(2.2, 3.2, 3.6) mm. No significant associations
were observed between inter-fraction shifts and tumor location or volume. Using
CBCT for image guidance reduced the observed errors to MUsetup=(-0.3, 0.1, 0.0)
mm, Sigmasetup=(0.6, 0.6, 0.4) mm and ssetup=(1.2, 0.7, 0.7) mm. Dosimetric
consequences for the patient with the largest setup error were explored. It was
shown that a 3.0 mm setup margin was sufficient to provide greater than 95% dose
coverage to the ITV. CONCLUSION: CBCT image guidance reduced setup errors
significantly such that 2-3 mm, population-based, setup margins provided proper
dose coverage to the ITV. Further investigation of inter-and intrafraction error
classification by tumor location is warranted.
PMID- 28518699
TI - TU-G-BRB-04: A Robust-CVaR Optimization Approach to Left-Sided Breast IMRT.
AB - PURPOSE: To test the feasibility of a cardiac sparing IMRT planning approach for
patients with left-sided breast cancer using a robust optimization model.
METHODS: A robust optimization model was developed for breast IMRT. The concept
of conditional-value-at-risk (CVaR) was used in the robust framework to guarantee
that the clinical dose volume criteria for targets and organs at risk hold under
uncertainty in the patient's breathing pattern. Clinical treatment methods for
breast cancer (inhale breath-hold with active breathing control (ABC) or free
breathing) were simulated via optimization models. A 4DCT patient dataset with
target and organs at risk on each breathing phase was used to simulate a clinical
case with a total of 20% increase in lung volume from exhale to inhale over 5
phases. The results of the proposed robust model were compared with those of the
current clinical models. RESULTS: Compared to the conventional IMRT method for
breast cancer (with free breathing), the proposed robust-CVaR model resulted in a
14.6% reduction in mean heart dose without compromising the target coverage and
dose homogeneity. The clinical dose-volume limits for the heart as well as the
clinical target volume were met in robust results. The robust method resulted in
23.9% improvement in the maximum dose to 25cc of the heart volume. The robust
results showed very low variability among the quality of planning and realized
treatments. CONCLUSIONS: Using CVaR limits in a robust optimization framework can
help improve the quality of IMRT treatments. The robust-CVaR can generate a high
quality treatment plans, but is delivered during free breathing and does not
require patient compliance with an external device. The quality of robust
treatment remains the same under irregular breathing. Explicitly including
metrics for lung and bigger motion amplitudes in the robust optimization method
may further improve the results.
PMID- 28518701
TI - TU-G-213AB-01: Organization and Productivity Strategies for Practicing Medical
Physicists.
AB - : Medical physicists face numerous challenges that create stress in the
professional workplace. The modern work environment contains multiple
communications channels, such as email, smart phones, text and instant messaging,
voice mail, pagers, and more. These media make it difficult to organize incoming
information, set priorities, and move important work forward in the face of rapid
change and the requirement to fulfill multiple responsibilities. Medical
physicists in particular are likely to feel acute stress due to off-peak work
hour requirements, varied responsibilities including clinical duties, research,
teaching, and regulatory matters, and the complexity of supervising other staff
members. Many medical physicists also work in multiple physical locations, adding
complexity to the task of organizing information and resources. Another common
difficulty is that medical physicists' responsibilities typically include some
duties that render them subject to frequent and urgent interruption, such as
emergency response coverage for radiation safety. The real challenges in the
current medical physics work environment differ from those encountered while
taking courses and conducting research, as well as from earlier periods when
medical physicists faced fewer varied responsibilities, slower-paced change, or
both. Today's practicing physicist can benefit greatly from developing a formal
framework and skill set to manage their personal workflow. This greatly increases
the individual's effectiveness and reduces feelings of stress, while improving
the effectiveness of teams or groups in which they participate. In this session,
participants will learn about a number of techniques and strategies to manage
their own personal workflow. Examples familiar to the medical physicist will be
provided to illustrate methods to capture, organize, and act on important
information, to delegate effectively, and to handle inevitable interruptions.
LEARNING OBJECTIVES: 1. Describe the use of a personal workflow in managing
ongoing or routine clinical physics duties. 2. Select an appropriate method for
filing various documents and records commonly encountered in medical physics. 3.
Implement strategies for minimizing the impact of interruptions on the
physicist's daily work.
PMID- 28518700
TI - TU-E-BRB-01: Similar-Case-Based Optimization of Beam Arrangements in Stereotactic
Body Radiation Therapy.
AB - PURPOSE: The quality of a treatment plan for stereotactic body radiotherapy
(SBRT) depends on an experience of each treatment planner. Therefore, the
treatment plans are subjectively determined by comparison of several treatment
plans developed by time consuming iterative manners, while considering the
benefit to a tumor and the risk to the surrounding normal tissues. The aim of our
study was to develop an automated optimization method for beam arrangements based
on similar cases in a database including plans designed by senior experienced
treatment planners. METHODS: Our proposed method consists of three steps. First,
similar cases were automatically selected based on image features from the
treatment planning point of view. We defined four types of image features
relevant to planning target volume (PTV) location, PTV shape, lung size, and
spinal cord positional features. Second, the beam angles of the similar case were
registered to the objective case with respect to lung regions using a linear
registration technique. Third, the beam direction of the objective case was
locally optimized based on the cost function considering radiation absorption in
normal tissues and organs at risk. The proposed method was evaluated with 10 test
cases and a treatment planning database including 81 cases by using eight
planning evaluation indices such as D95, lung V20, and maximum spinal cord dose.
RESULTS: The proposed method may provide usable beam directions, which have no
statistically significant differences with the original beam directions (P >
0.05) in terms of the seven planning evaluation indices. Moreover, the mean value
of D95 for 10 test cases was improved with a statistically significant difference
by using the proposed method, compared with the original beam directions (P =
0.03). CONCLUSIONS: The proposed method could be used as a computer-assisted
treatment planning tool for determination of beam directions in SBRT.
PMID- 28518702
TI - TU-E-BRA-01: A Comparison of Various Online Strategies to Account for
Interfractional Variations for Pancreatic Cancer.
AB - PURPOSE: To indentify effective methods to address the large interfractional
variations for pancreas irradiation, we compared various used/proposed online
strategies. METHODS: The daily CTs acquired using a respiration-gated in-room CT
for 9 pancreatic cancer patients treated with IGRT (i.e., online repositioning
based on rigid-body alignment) were analyzed. The contours of the pancreas and
duodenum on each daily CT set were generated by populating those from the
planning CT using a deformable registration tool (ABAS, Elekta) with manual
editing. PTV was generated with 3 mm margin. Nine online strategies were
considered: 1) IGRT with 0 mm additional margin (AM), 2) IGRT with 2mm AM, 3)
IGRT with 5mm AM, 4) IGRT with plan renormalized to maintain 95% PTV coverage, 5)
Full scale reoptimization, 6) Reoptimization starting from the original plan, 7)
Segment Aperture Morphing (SAM) from the original plan based on PTV shape change
8) SAM plus Segment Weight Optimization (SWO), 9) Reoptimization starting from
the SAM plan. One way ANOVA (analysis of variance) was applied to plan qualities
for the 9 strategies to assess statistical significance in difference. RESULTS:
The standard IGRT strategies (1-3) resulted in either inadequate PTV coverage or
higher duodenum doses. Margin expansion along is not efficient to account for the
changes. Full-scale reoptimization resulted in the best plan but requiring
delineation of several structures. Reoptimization on top of available plan
(strategies 6 and 9) was considerably faster. SAM strategy (7) is the fastest
online replanning, as it requires only one structure (target) delineation, and
it's plan quality was comparable to that for the full-scale reoptimization.
CONCLUSION: Online replanning strategies can lead to either reduced duodenum dose
or improved target coverage as compared to the current practice of IGRT. The SAM
based online replanning is comparable to the full scale reoptimization and is
efficient for practical use.
PMID- 28518703
TI - TU-E-213CD-01: Image Guided Adaptive Brachytherapy for Cervical Cancer.
AB - : Image-guidance plays an important role in modern radiation therapy,
predominantly in external beam planning and delivery. In contrast, brachytherapy
is still largely based on systems originally developed in the early 20th century.
In recent years, with the advent of high/pulsed dose rate (HDR/PDR) afterloading
technology, advanced treatment planning systems and CT and MRI compatible
applicators, image-guided adaptive brachytherapy treatments are now achievable.
With image guidance, the target can be delineated more precisely, resulting in
delivering more controlled doses of radiation to the target while sparing
surrounding healthy tissue. GEC-ESTRO guidelines are crucial for implementing
robust and standardized image guided adaptive brachytherapy (IGABT). They rely on
MRI-guided planning for cervical cancer. MRI can be performed for each
brachytherapy (BT) fraction to adaptively plan and deliver the desired radiation
dose with less toxicity to surrounding tissues. MR imaging has its advantages,
but also challenges and limitations (image artifacts and distortion related to
magnetic nonlinearity, MR sequence selection, accuracy of 3D applicator
reconstruction) that need addressed. Moreover, MRI technology is not readily
available in most Radiation Oncology departments, making its implementation hard.
In such settings, CT or US-based planning can be used despite lacking the desired
soft tissue resolution to accurately depict the target. Hybrid approaches have
been proposed, where a first BT fraction is planed based on MRI, and subsequent
fractions are performed with CT-guidance. Moreover, new
intracavitary/interstitial applicators are becoming available and data from
centers using existent applicators is maturing. Regardless of the type of
adaptive image guided and applicators used, there are still ongoing debates
regarding the prescription, the relevance of point A dose, treatment planning in
general, and the use of inverse planning in particular, role of model-based dose
calculation algorithms, adaptive strategies, intrafraction variability, in-vivo
dosimetry, dose summation with external beam treatments, to mention just some of
the challenges raised by implementing this treatment technique. This symposium is
proposing to address all of these issues and update the community at large on the
status of image guided adaptive brachytherapy for cervical cancer. LEARNING
OBJECTIVES: 1. To discuss the physics perspective of role of IGABT in management
of cervical cancer. 2. To compare IGABT approaches: MRI, CT, US, and Hybrid 3. To
present the advantages, challenges, and limitations of MRI for IGABT. 4. To
discuss hot topics in IGABT including planning strategies, role of model-based
dose calculation algorithms, new applicators, dose specification.
PMID- 28518704
TI - TU-C-218-02: Effective Oncology Physics Education.
AB - : The education of medical physicists has historically been quite varied and
medical physicists have entered the field through several pathways including
specialized educational programs, postdoctoral fellowships, and on-the-job
training. It is argued that the contributions of viewpoints from different
branches of physics has contributed to the development of novel solutions and
advances in radiation oncology. However, there also has been an effort recently
to make graduate education of medical physicists more consistent and uniform,
particularly for the preparation of clinically oriented therapy physicists. The
trend towards a more systematic approach has been guided in part by the
requirements for graduate program accreditation developed by CAMPEP and by the
requirements for medical physicist certification by the ABR. At the same time,
there has been criticism of this approach as being too confining and guiding
graduates toward a career as technicians rather than independent thinkers.
Educational programs have had to balance the requirements of accreditation and
certification against the goal of preparing students for careers as independent
researchers. Three speakers will describe the approaches taken by their graduate
educational programs to meet the requirements of CAMPEP and adequately prepare
graduates for certification by the ABR, while maintaining a commitment to
providing a comprehensive education in medical physics. LEARNING OBJECTIVES: 1.
Understand the requirements for graduate program accreditation 2. Understand the
education and experience requirements for certification 3. Learn the approaches
taken by several graduate programs to meet the requirements for accreditation and
certification while providing a comprehensive education in medical physics.
PMID- 28518705
TI - TU-E-217BCD-11: Evaluating the Performance of a Stationary Digital Breast
Tomosynthesis System.
AB - PURPOSE: In conventional Digital Breast Tomosynthesis (DBT) systems a single x
ray source moves over a limited angle arc. This leads to motion blurring in the
projection images associated with x-ray source motion and total scan times. We
have developed a stationary DBT (s-DBT) system which forgoes a rotating source
for an array of carbon nanotube (CNT) based x-ray sources. Here we report the
results of evaluating the performance and the optimization of image acquisition
parameters of the s-DBT system. METHODS: The s-DBT system consists of a linear
source array with 31 x-ray generating focal spots distributed over a 30 degree
angular span. The source array has been retrofitted onto a Hologic Selenia
Dimensions DBT system. An American College of Radiology accreditation phantom was
imaged to assess the quality of the reconstruction images in different
configurations. A line wire phantom is used to measure the modulation transfer
function (MTF). RESULTS: For the standard imaging protocol, the system resolution
along the scanning direction is increased from 3.0 cycles/mm in DBT to 4.2
cycles/mm in s-DBT at a magnification factor of 1.08. The MTF did not have a
noticeable change between different configurations, whereas in DBT the MTF can be
degraded for larger angular spans due to faster x-ray source motion. The overall
image quality factor is found to be best for the configuration with a large
angular span and intermittent number of projection views. CONCLUSIONS: We
demonstrated successful construction and operation of the s-DBT system
integrating a CNT x-ray source array with a Hologic DBT system. The spatial
resolution of the s-DBT system is demonstrated to be substantially increased over
the corresponding DBT system. It was found that a configuration with a large
angular span, an intermittent number of projection views, and an even dose
distribution resulted in the best overall image quality. Hologic INC has provided
the Hologic Selenia Dimensions used in the research. The project is supported by
the National Cancer Institute under grant number U54CA119343 and R01CA134598 and
the UNC University Cancer Research Fund. Dr. Xin Qian is supported by a
fellowship from the Department of Defense under grant number BC087505.
PMID- 28518706
TI - TU-E-BRB-05: Impact of Interfractional Tumor Motion on Respiratory Gated
Stereotactic Body Radiation Therapy for Lung Tumors.
AB - PURPOSE: To investigate the impact of interfractional tumor motion on dose
delivery of gated lung SBRT. METHODS: 4DCT scan for five lung patient was
performed without breathing control at simulation and prior to each treatment.
Gated treatment plans were performed on the end-exhale (50% phase) simulation CT
with a 30% duty cycle. ITV was created by combining the GTVs at 40%, 50% and 60%
phases. PTV was created by adding a 5 mm uniform margin to the ITV. All plans
were normalized such that 60 Gy (3 fractions) was prescribed to the 85% isodose
line. To calculate the accumulated dose over the treatment course, the original
plan parameters were copied to the 40%, 50% and 60% CTs obtained prior to each
treatment. In order to eliminate the effect of setup error to dose delivery,
treatment isocenters at each fraction were determined by aligning the tumors on
the slow CTs obtained prior to each treatment to that on the slow simulation CT.
Doses recalculated on the 40% and 60% CTs at each fraction were warped through
deformable CT image registration to their corresponding 50% CT to compose the 4D
dose at that fraction. Those fractional 4D doses were warped to the 50%
simulation CT to compose the accumulated 4D dose over the treatment course.
RESULTS: The minimum tumor doses over the treatment course were 59.9, 45.1, 68.9,
41.9 and 47.8 Gy respectively. Tumor V60s were 99.7, 92.2, 100, 97.2 and 93.0%
respectively. The corresponding mean lung doses were 3.8, 6.4, 3.7, 4.4 and 3.7
Gy respectively. CONCLUSIONS: Change in tumor motion pattern over the treatment
course results in tumor underdosing. Tight margins are normally used in lung
SBRT. Therefore monitoring of the reproducibility of interfractional tumor motion
is critical to the success of dose delivery.
PMID- 28518707
TI - TU-G-BRCD-02: Do Uncertainties in Proton Therapy Limit Its Clinical Potential?
AB - PURPOSE: To discuss uncertainties in proton therapy and to outline how these
might impact the widespread use of proton therapy. METHOD AND MATERIALS: This
presentation will outline some of the differences in treatment planning for
proton therapy as compared to photon therapy, in particularly related to the
finite range of proton beams. The source of range uncertainties (e.g. dose
calculation and treatment delivery) and some methods to address them will be
presented. As examples we will discuss uncertainties in dose calculation in
highly heterogeneous media (head and neck). Examples for in-vivo dose
verification using dosimetric and imaging techniques in proton therapy will be
outlined. Planning strategies to address uncertainties will be presented.
Uncertainties due to the difference in biological effectiveness between proton
and photon therapy will be addressed briefly. RESULTS: The difference in physics
between photon and proton interactions causes proton therapy to be associated
with different type of uncertainties than photon therapy. These affect treatment
planning decisions and can influence whether proton therapy does show a
significant clinical advantage. Theoretical advantages in proton dose
distributions as compared to photon therapy do not necessarily translate in
clinical gains. Exceptions are, for example, pediatric patients where the
reduction in integral dose causes significant improvements in treatment outcome
as compared to conventional radiation Conclusions: Proton therapy is being used
increasingly in radiation therapy. Due to inherent uncertainties in proton
therapy delivery, its full potential advantage cannot yet be reached for all
sites. Proton therapy personnel needs to be aware of the subtleties of proton
therapy. LEARNING OBJECTIVES: 1. To understand how treatment planning decisions
in proton therapy differs from photon therapy 2. To understand the source and the
magnitude of proton range uncertainties 3. To understand how uncertainties in
proton therapy affect the acceptance and spread of this modality.
PMID- 28518708
TI - TU-E-BRA-05: Reverse Geometry Imaging with MV Detector for Improved Image
Resolution.
AB - PURPOSE: Thick pixilated scintillators can offer significant improvements in
quantum efficiency over phosphor screen megavoltage (MV) detectors. However
spatial resolution can be compromised due to the spreading of light across pixels
within septa. Of particular interest are the lower energy x-ray photons and
associated light photons that produce higher image contrast but are stopped near
the scintillator entrance surface. They suffer the most scattering in the
scintillator prior to detection in the photodiodes. Reversing the detector
geometry, so that the incident x-ray beam passes through the photodiode array
into the scintillator, allows the light to scatter less prior to detection. This
also reduces the Swank noise since now higher and lower energy x-ray photons tend
to produce similar electronic signals. In this work, we present simulations and
measurements of detector MTF for the conventional/forward and reverse geometries
to demonstrate this phenomenon. METHODS: A tabletop system consisting of a Varian
CX1 1MeV linear accelerator and a modified Varian Paxscan4030 with the readout
electronics moved away from the incident the beam was used. A special holder was
used to press a 2.5W*5.0L*2.0Hcm3 pixellated Cesium Iodide (CsI:Tl) scintillator
array on to the detector glass. The CsI array had a pitch of 0.784mm with plastic
septa between pixels and the photodiode array pitch was 0.192 mm. The MTF in the
forward and reverse geometries was measured using a 0.5mm thick Tantalum slanted
edge. Geant4-based Monte Carlo simulations were performed for comparison.
RESULTS: The measured and simulated MTFs matched to within 3.4(+/-3.7)% in the
forward and 4.4(+/-1.5)% in reverse geometries. The reverse geometry MTF was
higher than the forward geometry MTF at all spatial frequencies and doubled to
.25 at 0.3lp/mm. CONCLUSIONS: A novel method of improving the image resolution at
MV energies was demonstrated. The improvements should be more pronounced with
increased scintillator thickness. Funding support provided by NIH (grant number
NIH R01 CA138426).
PMID- 28518709
TI - TU-E-217BCD-04: Spectral Breast CT: Effect of Adaptive Filtration on CT Numbers,
CT Noise, and CNR.
AB - PURPOSE: Photon counting spectral breast CT is feasible in part due to using an
adaptive filter. An adaptive filter provides flat x-ray intensity profile and
constant x-ray energy spectrum across detector surface, decreases required
detector count rate, and eliminates beam hardening artifacts. However, the
altered x-ray exposure profiles at the breast and detector surface may influence
the distribution of CT noise, CT numbers, and contrast to noise ratio (CNR)
across the CT images. The purpose of this work was to investigate these effects.
METHODS: Images of a CT phantom with and without adaptive filter were simulated
at 60kVp, 90kVp, and 120kVp tube voltages and 660 mR total skin exposure. The CT
phantom with water content had 14cm diameter, contrast elements representing
adipose tissue and 2.5mg/cc iodine contrast located at 1cm, 3.5cm, and 6cm from
center of the phantom. The CT numbers, CT noise, and CNR were measured at
multiple locations for several filter/exposure combinations: (1)without adaptive
filter for 660mR skin exposure; (2)with adaptive filter for 660mR skin exposure
along central axis (mean skin exposure across the breast was <660mR); and (3)with
adaptive filter for scaled exposure (mean skin exposure was 660mR). RESULTS: Beam
hardening (cupping) artifacts had 47HU magnitude without adaptive filter but were
eliminated with adaptive filter. CNR of contrast elements was comparable for (1)
and (2) over central parts but was higher by 20-30% for (1) near the edge of the
phantom. CNR was higher by 20-30% in (3) as compared to (2) over central parts
and comparable near the edges. CONCLUSIONS: The adaptive filter provided: uniform
distribution of CT noise, CNR, and CT numbers across CT images; comparable or
better CNR with no dose penalty to the breast; and eliminated beam hardening
artifacts.
PMID- 28518710
TI - TU-E-213AB-01: JMPSLC Has Morphed into Medical Physics Licensure and Regulatory
Recognition Subcommittee.
AB - Based on direction from AAM Board of Directors, JMPLSC has redefined its scope
and name. On November 4, 2011 the subcommittee renamed itself the Medical Physics
Licensure and Regulatory Recognition Subcommittee. Its newly defined charge is to
promote the protection of the public through the recognition of the profession of
medical physics by legislation or regulation. The following pathways shall be
implemented. 1. Recognition of the profession of medical physics through
licensure by legislation: a. Support the formation and activities of state
committee focused on professional licensure b. Provide model legislation c.
Provide consultation on regulatory language to implement professional licensure
2. Recognition of the profession of medical physics through regulation. a.
Support the formation and activities of state committee focused on the regulatory
approach b. Provide model regulation c. Provide consultation on regulatory
language to implement professional licensure d. Collaborate with the CRCPD
Subcommittee 3. Annually prepare status of subcommittees' activities. This
presentation will describe recent efforts of the subcommittee and report on its
successes, challenges and works in progress.
PMID- 28518711
TI - TU-F-BRCD-01: Tolerance Levels and Methodologies for IMRT Verification QA.
AB - : Intensity modulated radiation therapy (IMRT) is a technology intensive
treatment modality involving the delivery of highly conformal dose distributions
to patients. IMRT is becoming a standard of care for many disease sites and
approximately 30%-60% of cancer patients in the United States receive IMRT
treatments. Given the complexity of the IMRT treatment planning and delivery
processes, a number of AAPM reports and guidance documents addressed the
technical aspects of IMRT, including the need for comprehensive acceptance
testing, commissioning, and QA programs for IMRT planning and delivery equipment.
The implementation of these verification programs is essential to ensure the
accuracy of IMRT delivery. Despite the critical role of patient-specific IMRT
verification QA to ensure the safe delivery of IMRT treatments to patients as
planned, there is little systematic guidance on the type of methodologies, tools,
and acceptable tolerance levels that are needed in clinical practice.
Furthermore, there are limited discussion on the pros and cons of the different
delivery methods for QA measurements, and no recommendations on how to assess the
clinical relevance of failed IMRT plans. LEARNING OBJECTIVES: 1. To discuss
commonly employed IMRT measurement methods and discuss the pros and cons of each
method. 2. To review methodologies for absolute dose verification (single small
volume, 1D, 2D methods), and review dose-difference, DTA, and Gamma analysis
techniques including the variability of vendors implementation 3. To review IMRT
QA passing rates for given tolerances and action levels, and discuss the clinical
relevance of failed IMRT QA.
PMID- 28518712
TI - TU-E-BRB-09: Validation of Multi-Focal Stereotactic Radiosurgery with Volumetric
Modulated Arc Therapy with High-Resolution 3D Dosimetry.
AB - PURPOSE: Volumetric modulated arc therapy (VMAT) enables stereotactic
radiosurgery (SRS) treatment for multiple lesions with a single isocenter setup.
Dosimetry verification is highly challenging however, and the purpose of this
study is to validate this new treatment using novel 3D dosimetry techniques, with
potential for dramatically more comprehensive verification than possible with
conventional approaches. METHODS: A cylindrical PRESAGE dosimeter was inserted
into an RPC type head phantom for treatment validation. The phantom was
immobilized with an SRS U-frame system and a set of simulation CT images was
acquired with a SRS localizer. A 5-arc VMAT multi-focal SRS plan was created to
treat 5 intracranial lesions simultaneously. A set of cone-beam CT (CBCT) images
was then acquired to localize the isocenter, and the VMAT plan delivered to the
combined phantom. The PRESAGE dosimeter was then removed and scanned by optical
computed-tomography (optical-CT). The 3D PRESAGE dose measurement was
reconstructed with 1 mm resolution. Another PRESAGE insert with a pre-drilled ion
chamber channel was placed in the phantom and an SRS ion chamber was mounted for
an absolute dose measurement. The phantom was again localized with CBCT and the
VMAT plan was delivered. The dose measured with the ion chamber was compared with
calculated dose. RESULTS: The mean planned and PRESAGE measured doses to target 1
were 12.1Gy and 12.2 Gy, 18.7 Gy and 18.5 Gy for target 2, 18.6 Gy and 18.4 Gy
for target 3, 15.5 Gy and 15.4 Gy for target 4, 18.7 Gy and 19.0 Gy for target 5.
The 3D gamma passing rate was 95.6% for 3% and 1mm. The ion chamber measured dose
was within 1% of the planned dose. CONCLUSIONS: Our 3D PRESAGE dose measurement
shows that multi-focal VMAT is a valid technique for single isocenter SRS
treatment of multiple lesions. This research is partially supported by NCI
R01CA100835. This research is partially supported by NCI R01CA100835.
PMID- 28518713
TI - TU-G-BRB-03: Iterative Optimization of Normalized Transmission Maps for IMRT
Using Arbitrary Beam Profiles.
AB - PURPOSE: Newly available flattening filter free (FFF) beam increases the dose
rate by 3~6 times at the central axis. In reality, even flattening filtered beam
is not perfectly flat. In addition, the beam profiles across different fields may
not have the same amplitude. The existing inverse planning formalism based on the
total-variation of intensity (or fluence) map cannot consider these properties of
beam profiles. The purpose of this work is to develop a novel dose optimization
scheme with incorporation of the inherent beam profiles to maximally utilize the
efficacy of arbitrary beam profiles while preserving the convexity of the
optimization problem. METHODS: To increase the accuracy of the problem formalism,
we decompose the fluence map as an elementwise multiplication of the inherent
beam profile and a normalized transmission map (NTM). Instead of attempting to
optimize the fluence maps directly, we optimize the NTMs and beam profiles
separately. A least-squares problem constrained by total-variation of NTMs is
developed to derive the optimal fluence maps that balances the dose conformality
and FFF beam delivery efficiency. With the resultant NTMs, we find beam profiles
to renormalized NTMs. The proposed method iteratively optimizes and renormalizes
NTMs in a closed loop manner. RESULTS: The advantage of the proposed method is
demonstrated by using a head-neck case with flat beam profiles and a prostate
case with non-flat beam profiles. The obtained NTMs achieve more conformal dose
distribution while preserving piecewise constancy compared to the existing
solution. CONCLUSIONS: The proposed formalism has two major advantages over the
conventional inverse planning schemes: (1) it provides a unified framework for
inverse planning with beams of arbitrary fluence profiles, including treatment
with beams of mixed fluence profiles; (2) the use of total-variation constraints
on NTMs allows us to optimally balance the dose confromality and deliverability
for a given beam configuration. This project was supported in part by grants from
the National Science Foundation (0854492), National Cancer Institute (1R01
CA104205), and Leading Foreign Research Institute Recruitment Program by the
Korean Ministry of Education, Science and Technology (K20901000001-09E0100
00110). To the authors' best knowledgement, there is no conflict interest.
PMID- 28518714
TI - TU-E-BRA-09: Evaluation of a Patient-Specific Respiratory Motion Model in
Thoracic and Abdominal Phantom and Patient CT Images.
AB - PURPOSE: We have previously described a model of patient-specific respiratory
motion to predict organ deformations without assuming repeatable breath cycles.
The model is derived from deformable image registration (DIR) between respiration
correlated images (RCCT), followed by a principal component analysis (PCA) which
relates the first two principal components of 3D deformations to the position and
direction of motion of the diaphragm or implanted fiducials. This study examines
model accuracy in phantom and patient images. METHODS: We compare model and DIR
accuracy using 3 types of image sets, each exhibiting different deformation
patterns: (1) synthetic images in lung and abdomen from the 4D NURBS-based
cardiac torso (NCAT) phantom with known deformations; (2) CT scans of physical
deformable phantom with implanted markers in liver; and (3) liver structures in
patient RCCT images using rigid registration in a small VOI as approximate ground
truth. The model is calibrated by applying fast free-form DIR between a reference
image set at end expiration and each of the other images at different motion
states, defined by diaphragm or, in some patient cases, implanted fiducials as
surrogate signals. Following PCA, the first two principal components are selected
to yield a model-predicted displacement field for the given surrogate signal.
RESULTS: Discrepancy between model prediction and ground truth (mean +/- stand
deviation) in 3D displacements is 3.3+/-2.0 mm in lung and 3.7+/-1.9 mm in
abdomen in NCAT phantom, 3.8+/-2.7 mm in physical deformable phantom and 2.8+/
2.9 mm in patient data (N=7). Corresponding DIR discrepancies are 3.8+/-2.0 mm
(NCAT lung), 3.7+/-1.8 mm (NCAT abdomen), 3.6+/-2.8 mm (physical phantom), and
2.0+/-2.2 mm (patient data). CONCLUSIONS: Motion model accuracy is found to be
comparable to fast free-form in all three types of images, indicating that the
assumption of two principal components is sufficient to describe the fast free
form DIR-derived deformations. NIH/NCI award R01 CA126993.
PMID- 28518732
TI - Erratum: "Automatic patient alignment system using 3D ultrasound" [Med. Phys.
40(4), 041714 (7pp.) (2013)].
PMID- 28518891
TI - SU-E-J-134: Motion Modeling of Non-Small Cell Lung Nodules Based on Respiratory
Mechanics.
AB - PURPOSE: To quantify the movements of non-small cell lung nodules using 4D cone
beam computed tomography (4D-CBCT) that is automatically registered with planning
CT, and to develop a mathematical model to predict the motion trajectory.
Modeling the tumor motion may reduce the PTV and ultimately increase the
therapeutic ratio. METHODS: Absolute coordinates of the lung nodules in 15
patients were quantified for each phase of 4D-CBCT scans using auto-registration
methods. Assuming respiration follows an elliptical pattern spatially in the
lung, these coordinates were fitted to trigonometric functions in each x-y-z
direction. Adjusting for phase dependence, the motion could be compared
quantitatively for inter-fractional and intra-patient variations to determine if
this model is universally applicable and has predictive value. RESULTS:
Examination of over 36 sets of 4D-CBCT data shows acceptable agreement (< 2mm)
with the elliptical model for both individual scans and over the course of
treatment. Some inter-fractional variations in amplitude and cycling periods
indicate the need to remodel as patients' conditions change. The intra-patient
variations are significant and strongly dependent on the patient lung volume and
tumor location, thus individual modeling of tumor motion is expected.
CONCLUSIONS: The model indicates good agreement and clinical relevance with non
small cell lung nodule motion, and it appears to be potentially relevant over the
course of treatment. Most re-acquired 4D-CBCT images inter-fractionally were
within the baseline spatial resolution of the auto- registration technique.
However, if remodeling is necessary inter-fractionally, this model still has the
potential for significant motion margin reduction over the course of treatment.
PMID- 28518892
TI - SU-E-J-145: Implementing 4D XCAT Phantom for 4D Radiotherapy Research.
AB - PURPOSE: To characterize and implement the 4D Integrated Extended Cardiac Torso
(XCAT) digital phantom for 4D radiotherapy (RT) application. METHODS: A computer
program was developed to facilitate the characterization and implementation of
the 4D XCAT phantom. The program can (1) generate 4D XCAT images with customized
parameter files; (2) review 4D XCAT images; (3) generate composite images from 4D
XCAT images; (4) track motion of selected region-of-interested (ROI); (5) convert
XCAT raw binary images into DICOM format; (6) analyze clinically acquired 4DCT
images and Real-time Position Management (RPM) respiratory signal. Validation of
the motion tracking algorithm was made by comparing to manual method. Major
characteristics of the 4D XCAT phantom were studied including the dependence of
lesion motion on its location/size and inputted diaphragm profile. An end-to-end
test from image generation to treatment planning was also performed. RESULTS: The
comparison between motion tracking and manual measurements of lesion motion
trajectory showed a small difference between the two (mean difference in motion
amplitude: 1.2 mm). The maximum lesion motion decreased nearly linearly (R2=0.97)
as its distance to the diaphragm (DD) increased. At any given DD, lesion motion
amplitude increased nearly linearly (R2 range: 0.89 to 0.95) as the inputted
diaphragm motion increased. For a given diaphragm motion, the lesion motion is
independent f the lesion size at any given DD. The 4D XCAT phantom can closely
reproduce irregular breathing profile: the mean difference in motion amplitude
between the inputted and the measured motion profile was 1.4 mm. The end-to-end
test showed that clinically comparable treatment plans can be generated
successfully based on 4D XCAT images. CONCLUSIONS: An integrated computer program
has been developed to generate, review, analyze, process, and export the 4D XCAT
images. A robust workflow has been established to implement the 4D XCAT phantom
for 4D RT application.
PMID- 28518893
TI - SU-E-J-154: Advantages of Treating Thoracic Cancer Patients in an Upright
Position.
AB - PURPOSE: To compare lung volume and respiratory motion in supine and upright
positions to assess the potential advantages of treating thoracic cancer patients
in an upright position. METHODS: A multi-position MRI scanner (FONAR, Melville,
NY) was used to take MRI images of 4 healthy volunteers in both supine and
upright setup positions (expected total accrual: 15 volunteers). In each case, a
volumetric scan was acquired during breath-hold at end of normal expiration,
followed by a series of sagittal cine MR scans taken during normal respiration.
The exhale volume images were imported into a treatment planning system and lung
volumes were delineated and compared for different setup positions. The
trajectory of points inside the lung were tracked in the cine images and analyzed
using a deformable image registration technique and a principal component
analysis (PCA) model. RESULTS: The average exhale lung volume was 38% (894cc)
larger (range: 23%-57%, 570-121 1cc) when volunteers were in the upright position
compared with the supine position. The amplitude of motion for a set of landmark
points in the lung volume ranged from <2mm (distant from the diaphragm) to 29 mm
(close to the diaphragm) in the superior-inferior direction. A linear fit to the
amplitude of respiratory motion vs. distance from the diaphragm for all 4
volunteers indicated no difference on averagein the range of motion for the two
setup positions, but there was variability between individuals. CONCLUSIONS:
While the magnitude of motion was similar, the absolute lung volumes were much
larger in the upright position than in the supine position, which suggests that
treating thoracic patients in the upright position may allow for a reduction in
the mean lung dose. The study was partially supported by a sponsored research
grant from Varian Medical Systems.
PMID- 28518894
TI - SU-E-J-127: An Initial Application of Evaluating Lung Tumor Motion Throughout
Radiotherapy.
AB - PURPOSE: We present a novel method for evaluating lung tumor motion incorporating
planning CT scan, imaging for patient localization, and during treatment
delivery. METHODS: Tumor motion is evaluated at three stages of the treatment
process. Following the acquisition of 4D CT scans for treatment planning, tumors
are contoured at one phase and registered to other phases to obtain tumor motion
patterns. Tumor motion prior to each treatment is evaluated by identifying tumors
directly on every raw projection of the daily localization CBCT scans. Finally,
tumor motion during treatment is evaluated by analyzing MV treatment beam images.
Every frame of image is evaluated as three components, each with separate DRRs:
all non-moving structures, the tumor, and other moving structures. The locations
of three components are determined though a registration process. In order to
quantify tumor motion, the cumulated probability, the percentage of time when the
tumor motion is equal to or smaller than a given range, is evaluated at every
stage. RESULTS: This methodology has been applied to five lung cancer patients
undergoing radiotherapy. More than 5400 frames from MV treatment beam images and
24 CBCT scans were acquired from 12 fractions. Both the average tumor position
and the cumulated probability with the range were evaluated. The tumor motion
ranges are generally larger than those obtained from 4D CT. Significant variation
in motion patterns was observed as well. CONCLUSIONS: Information obtained from
4DCT is insufficient for motion assessment. In contrast, our novel methodology is
capable of accurately characterizing lung tumor motion on a daily basis, without
the need for implanted fiducial markers and without additional imaging dose. It
provides daily verification that the tumor range is within prior estimates and
covered by the treatment planning volume. This research is supported by CPRIT
Individual Investigator Award RP110329.
PMID- 28518895
TI - SU-E-J-138: Fast 2-D Fiducial Marker Detection on Sequential MV Projections in
Arc Therapy.
AB - PURPOSE: To automatically detect intrafraction motion during arc radiotherapy for
prostate cancer patients by tracking fiducial markers in two-dimensional MV
images acquired using the treatment beam, in order to adjust radiation dose
accordingly. METHODS: Four fiducial gold markers are implanted in a patient's
prostate. Patients are irradiated using a Varian Linac 2100 C/D with RapidArc
upgrade (Varian Medical Systems, Palo Alto, CA). MV images (1024 * 768 pixels,
0.392 * 0.392 mm2 pixel size) acquired during a 360 degree gantry rotation at a
one second interval (5 degrees) are preprocessed by subtracting a smoothed
version of the image to retain only high image frequencies. Edge detection is
then applied, followed by a one pixel wide dilation and erosion to transform the
edges into contiguous regions. Next, our method searches the centers of visible
markers (i.e. not covered by the MLC), constrained by marker estimates from the
planning CT. This is done by finding all contiguous regions and maximizing a
marker-region distance criterion for every visible marker. A two-dimensional
estimate correction over consecutive projections is also implemented to improve
marker estimates during gantry rotation. RESULTS: We applied our method on four
treatment fractions of the same patient. As such, a total of 191 projections with
manually indicated marker ends as ground truth were used as validation. Markers
were indicated twice on all images, to include observer errors. Results show a
mean detection error of less than 0.5 mm in the projection image (standard
deviation 0.6 mm), with an execution time of less than one second per image in
matlab. Undetected markers and false positives mostly occurred at moving leaf
boundaries, where marker visibility was determined by the observer. CONCLUSIONS:
Preliminary findings demonstrate that this method can be used to detect
intrafraction motion during arc radiotherapy by only using projected MV images.
Research sponsored by Varian Medical Systems, Palo Alto, CA.
PMID- 28518896
TI - SU-E-J-148: Fabrication of an Anatomically Realistic Dynamic Respiratory Phantom.
AB - PURPOSE: The purpose of this project was to design an anatomically correct
respiratory phantom that allows for accurate dose measurement within thoracic
structures that move in a realistic fashion allowing for a more accurate
simulation of in vivo measurements. METHODS: The basis for this phantom is The
Dynamic Breathing Phantom (TBP), an Alderson Phantom by Radiology Support Devices
(RSD). The phantom was disassembled, removing the proprietary pneumatic lung
apparatus as well as the motor driven tumor mount. A CT of the phantom at rest in
the exhale position was acquired with 0.25 cm slice thickness. Every sixteenth
slice was printed out to scale. The lung cavity was segmented on the images.
These were used to cut out 4.0 cm thick slabs of foam rubber matching the contour
of the lung. These were assembled along with other thoracic structures manually
imbedded in the foam rubber. The organs were then placed within the chest cavity
of the phantom. A purpose-built diaphragm chamber made of a rubber bladder was
inserted under the lung material. The manufacturer-provided air compressor system
was re-tasked to drive the diaphragm chamber. RESULTS: The foam rubber used as
lung material has comparable density to human lung (-800 HU). The phantom is
capable of producing realistic respiratory motion. This phantom will easily
accommodate a variety of dosimeters and can be adapted for a variety of
tumor/critical structure shapes, sizes and locations. CONCLUSIONS: The creation
of this versatile humanoid phantom opens the door for a multitude of experiments
to investigate dose to organs within the chest cavity for different planning
techniques, under different respiratory condition, while using a more
anatomically correct experimental setup.
PMID- 28518898
TI - SU-E-J-158: A Prototype of a Real-Time Respiratory Motion Monitoring System Using
Microsoft Kinect Sensor.
AB - PURPOSE: To investigate the feasibility of a low-cost respiratory motion
monitoring system based on the Microsoft Xbox Kinect sensor. METHODS: We improved
Kinect's inherent depth resolution from 1 cm to 1 mm via a motion magnification
system. Using the Kinect software development kit, we programmed the Kinect to
capture depth images and determine the average depth over a thoracic region of
interest, viewed almost parallel to the subject's surface. Kinect respiratory
traces (average depth vs time at a rate of 30 Hz) were acquired from four
volunteers and compared with those simultaneously acquired using a commercially
available strain gauge respiratory gating system. RESULTS: The correlation
coefficient (CC) between Kinect and strain gauge traces varied from 0.958 to
0.978, with a mean CC of 0.969. This strong correlation was also demonstrated by
the joint probability distribution and visual inspection. CONCLUSIONS: This work
demonstrates the feasibility of using the Kinect for respiratory motion tracking.
Traces are similar to those of a clinically used strain gauge system. The Kinect
based system provides a new and economical way to monitor respiratory motion.
PMID- 28518899
TI - SU-E-J-131: Implement a Passive Breath Gating Equipment for Gated CBCT Imaging: A
Feasibility Study.
AB - PURPOSE: To investigate the feasibility of using a patient passive breath gating
(PBG) equipment in kilo-voltage cone-beam CT (kVCBCT) image acquisition to reduce
the respiratory induced motion artifacts for image-guided radiotherapy. METHODS:
A PBG equipment developed in our department was used to passively block patient's
breathing. Assisted by this device, patients were able to hold their breaths for
15-25 seconds. An infrared block was placed on the patient's body and the breath
hold was triggered by the signal from the Varian RPM system. Three sets of kVCBCT
images were acquired using the same imaging parameters with the OBI system on
Varian Trilogy for a gastric cancer patient: free breathing (FB), with two-breath
hold (BH1) and three-breath-hold (BH2). Patient was allowed to breathe normally
for 5-10s between breath-hold. A planning CT was obtained with one breath-hold on
a conventional 4D CT scanner. The diaphragm position on FB, BH1 and BH2 CBCT
images was compared with its position on the planning CT to assess the motion
artifacts. RESULTS: The acquisition time for each of the three kVCBCTs was 60
seconds. The patient tolerated the breath-hold CBCT scanning well. Severe image
blurriness and streak artifacts caused by respiratory motion were observed near
the diaphragm on FB CBCT. However, for the breath-hold CBCT images, the motion
artifacts were reduced and the diaphragm edge was restored. Two-breath-hold scan
(BH1) produced better image quality than three-breath-hold (BH2). The details of
the diaphragm edge on BH1 images were comparable to the planning CT. CONCLUSIONS:
Diaphragm motion causes image distortion in FB CBCT. The PBG can be used in
kVCBCT acquisition to reduce motion artifacts. The breath-hold kVCBCT can produce
higher image quality for image-guided radiotherapy and adaptive radiotherapy in
the thorax and abdominal regions. Conflict of Interest (only if applicable):
Research supported by Varian Medical System. This work is partly supported by
Varian Medical System.
PMID- 28518897
TI - SU-E-J-179: Requirements for the Accuracy of Electron Density Data Planning for
MRI Based Cervix Cancer Treatment Planning.
AB - PURPOSE: A sensitivity analysis of the effect of variations in electron density
data (ED) on dose calculation accuracy for MRI based cervical cancer treatment
planning. METHODS: Five cervical cancer patients were analysed in this work.
Planning CT scans represented gold standard ED data. Standard four field 3DCRT
plans (prescription 45Gy) were designed on these CT scans. The CT data was then
manipulated to simulate the following methods of assigning ED to MRI; (1)
homogenous bulk density corrections, (2) Bulk density correction to bones, (3)
rigid image registration of CT to MR, and (4) regression analysis based pseudo
CT. Plans were then generated on the manipulated data sets, and compared to the
plans generated on the original. Dose was analysed using Chi analysis and
equivalent uniform dose (EUD). Data was analysed to quantify (A) the effect on
plan design (called optimisation error), and (B) the effect on dose calculation
accuracy (systematic error). RESULTS: Analysis of the averaged patient results
showed that for 3DCRT, the use of imperfect electron density data had minimal
impact on plan design for all tested data sets. Analysis of systematic error
showed minimal errors for cases (1), (2) and (3), where average errors of less
than 0.3 Gy in EUD were recorded and Chi analysis showed that over 95% of points
within the high dose region (D>36Gy) were within 2% or 2mm of the original dose.
For case (4), errors greater than .5 Gy in EUD were recorded; these were not
considered acceptable errors. CONCLUSIONS: Using imperfect electron density data
for 3DCRT treatment planning for cervical cancer patients is feasible for
appropriately considered choices of electron density assignment. Further analysis
is needed to test this result for IMRT, and is ongoing.
PMID- 28518901
TI - SU-E-J-174: ITV Variations as a Function of CT Geometry and Scan Time : A
Simulation Study Using Patient Data.
AB - PURPOSE: The internal target volume (ITV) accounts for uncertainties in tumor
position and shape and is defined from images acquired with 4DCT. In this work,
the locations of gold fiducial markers implanted in lung tumors of seven patients
are used to represent tumor motion and investigate the role of the CT scanner
geometry and scan duration on ITV definition. METHODS: All of the simulations are
geometric simulations performed in MATLAB (The Mathworks, Nattick,MA) and
variations in image reconstruction are not considered. The CT scanner geometries
simulated include a 4-slice CT scanner (with an axial field of view of 10 mm) and
an 'ideal' CT scanner geometry that covers all potential tumor positions in the
same bed position (axial field of view of 100 mm). The scan durations were varied
from 6 seconds per bed position to 30 seconds per bed position. For all of the
simulations, the tumor was modeled as a sphere of diameter 25 mm. The ITVs were
compared by calculating the mean ITV for each patient and scan parameters.
RESULTS: For all of the patients, the mean ITV increased as the scan duration
increased. The maximum increase in mean ITV was 25%. CONCLUSIONS: This work
highlights the potential benefit of modified CT protocols to determine the ITV.
One example of a modified protocol would be to increase the scan duration (to
decrease ITV uncertainties) while decreasing the mA of the scanner (to avoid
giving extra radiation dose). The largest factor influencing the ITV is the scan
duration (and not the scanner geometry).
PMID- 28518900
TI - SU-E-J-142: Gafchromic Film Dosimetry in Fluoroscopy for Dynamic Tumor Tracking
Irradiation of the Lung Using XR-SP2 Model - A Phantom Study.
AB - PURPOSE: We have recently developed a dynamic tumor tracking irradiation system
using Vero4DRT (MHI-Tm2 000). It is needed to create a 4D correlation model
between a fiducial marker implanted near a tumor and an external surrogate as a
function of time by continuously acquiring both fluoroscopy images and external
surrogate signals. The purpose of this study was to propose a new dosimetry
method using Gafchromic XR-SP2 films to measure surface dose by fluoroscopy
imaging. METHODS: First, half-value layers (HVLs) were measured using aluminum
(Al) thicknesses (15 mm) at 40125 kVp. Subsequently, several films were
irradiated using various milliampere second values on a solid water phantom. The
surface air kerma were also measured using the chamber to calculate the surface
doses under the same condition. Then, the calibration curve of dose vs. pixel
values was calculated. Finally, surface dose by fluoroscopy imaging was measured
using several pieces of film taped on the chest phantom. Orthogonal X-ray
fluoroscopy imaging was simultaneously performed until completion of data
acquisition for creating a 4D correlation model. Those films were scanned after
irradiation using a flat-bed scanner and converted to dose by calibration curve.
RESULTS: The HVLs for tube voltage within 40125 kVp ranged from 2.35 to 5.98 mm
Al. The calibration curve between surface dose and pixel values was reasonably
smooth. The differences between the measured and the calibrated doses were less
than 3%. The hot spots with the maximum dose of 37.12 mGy were observed around
the area overlapped by both fluoroscopic fields. CONCLUSIONS: We have proposed a
new dosimetry method using Gafchromic XR-SP2 films to measure surface dose by
fluoroscopy imaging. This phantom study has demonstrated that it may be feasible
to assess surface dose to patients during dynamic tumor tracking irradiation in
clinic with ease after further investigation. This research was supported by the
Japan Society for the Promotion of Science (JSPS) through its Funding Program for
World-Leading Innovation R&D on Science and Technology (FIRST Program). Research
sponsored in part by Mitsubishi Heavy Industries, Ltd.
PMID- 28518903
TI - SU-E-J-167: Optimal Number of Respiratory Phases in 4D PET for Radiotherapy
Planning: Motion-Simulated Phantom Study.
AB - PURPOSE: Four-dimensional PET/CT is increasingly used in radiotherapy treatment
planning. One issue that is still under investigation is the optimal number of
bins or phases into which the respiratory cycle needs to be divided. We performed
4D PET moving phantom study and compared results between 6 and 10 bins. METHODS:
A Jaszczak PhantomTM containing six hollow spheres (0.95 - 3.18 cm inner
diameters) was used. Three sinusoidal motion patterns were accomplished with peak
to-peak amplitudes of 1, 1.5 and 2.0 cm with a respiratory period of 5 s. The
background and the six spheres were filled with 18F-FDG solution to achieve three
SBR: 1:3.65, 1:7.95, and 1:10.22. Data were collected in 3-D mode for 10 min.
Images were reconstructed using OSEM reconstruction: 32 subsets with 2
iterations, variable FWHM Gaussian post-filter 5-8 mm, and using image matrix
sizes of 128*128, 192*192 and 256*256. The spheres were auto-segmented using pre
calculated optimal thresholds for a 1:1 volumetric correlation between actual-
and PET-delineated spheres from static phantom studies. RESULTS: According to the
static data the following set of parameters are optimal for static PET target
(sphere) delineation: OSEM reconstruction with 32 subsets and 2 iterations, FWHM
of 5 mm, and image size 256*256. The 4D data studies (with pre-calculated optimal
thresholds) have shown that a 6-bin set shows less volume distortions then the 10
bin set. CONCLUSIONS: The authors found that 6-bin reconstruction is more
reliable for delineation of a target in motion than 10-bin reconstruction.
Further investigation with optimal thresholds obtained from 4D data, not static,
is required no conflict of interest for all authors.
PMID- 28518902
TI - SU-E-J-152: Prostate IGRT: CT-MRI Fusion and Target Delineation Accuracy.
AB - PURPOSE: The accuracy of CT-MR imaging fusion plays an important role in both
accurate delineation (using MR data) and dose calculation (using CT data) for
image-guided radiotherapy (IGRT) of prostate cancer. The purpose of this study
was to investigate the accuracy of CT-MRI fusion in target
delineation/localization for prostate IGRT. METHODS: Sixty-nine prostate patients
were included in this study. Each patient underwent CT/MR simulation prior to the
IMRT or RapidArc treatment. Paired CT-MR images were obtained using a GE 4D-CT
scanner and a GE 1.5T MR scanner. MR and CT scans were performed within 30min to
minimize organ or structure changes except for Calypso patients who received MR
scans prior to the Beacon implantation. Prostate, rectum and bladder were
delineated on CT and MRI, respectively. The difference of prostate centers and
the volume variation between CT and MRI were calculated and used as the index for
image fusion accuracy. RESULTS: With bony structure matching, all bony structures
were fused well between CT and MRI. However, the changes in bladder and rectum
fillings between CT and MRI dislocate the prostate and the surrounding
structures. The maximal shift of the prostate in the AP direction was up to 8mm
and about 15.9% of the patients showed a shift >3mm, which was proportional to
the difference of the rectum volume. The shift in the SI direction was 0.5-5mm.
Of the 11 patients who had >3mm shifts, 6 patients (54.5%) were Calypso patients.
CONCLUSIONS: Significant geometrical shifts of the prostate target were observed
correlated with large differences in the bladder/rectal volume between CT and MR
images especially for large CT-MRI intervals. Attention must be paid to the
residual fusion error for the soft tissue target and corrections should be made
to ensure target delineation accuracy if necessary.
PMID- 28518904
TI - SU-E-J-178: Development of Image Planning System for Radiation Therapy.
AB - PURPOSE: The constraints required for patient imaging dose received during image
guided radiotherapy differ from those applied in the diagnostic realm. Wide
latitude in applied dose can be justified if it results in useful improvement in
image quality. Currently, image acquisition parameters are chosen via broad
categorizations in patient anatomy and imaging goal. Herein, we describe the
development and early benchmarking of a patient-specific image planning system
that is capable of predetermining the optimal acquisition parameters for a given
level of patient dose and imaging goal. METHODS: An algorithm was written in
Matlab that performed a divergent ray-trace through a 3D CT data set and impinges
on a flat imaging receptor. Energy-specific attenuation through each voxel of the
CT data set is calculated to derive a net transmitted intensity. The detector
response as a function of beam quality and exposure was measured and integrated
into the algorithm. It is primarily this feature that distinguishes this from a
traditional digitally reconstructed radiograph. Verification data was collected
using a flat panel imager mounted onto a linear accelerator gantry and a lung
phantom with an embedded nodule. Loss of object detectability was evaluated by
measuring the visible diameter of the phantom nodule. RESULTS: There is
qualitative agreement between simulated and measured images in terms of contrast
and object detectability. The simulation algorithm predicts both under-exposure
and saturation of the detector over a range of beam qualities (80 keV to 120keV)
and exposure levels. Object detectability erodes predictably above 60 mAs for at
80keV and above 15mAs for 120 keV for both simulated and measured images.
Quantitative accuracy is currently limited by lack of beam heterogeneity, which
will be added in further work. CONCLUSIONS: The feasibility and qualitative
accuracy of an image planning system has been established.
PMID- 28518905
TI - SU-E-J-144: Recurrence Quantification Analysis of Lung Cancer Patients' Breathing
Pattern.
AB - PURPOSE: To demonstrate that Recurrence quantification analysis (RQA) can be used
as a quantitative decision making tool to classify patients breathing pattern and
select treatment strategy for maneuvering the tumor motion : (a) MIP based
treatment (b) 4D treatment using non-linear prediction only (c) 4D treatment non
linear control prediction and breathing control. METHOD AND MATERIALS: In our
previous work we established that breathing patterns can be described as a 5-6
dimensional nonlinear, stationary and deterministic system that exhibits
sensitive dependence on initial conditions. Recurrence plots enable one to
investigate an m-dimensional state space trajectory through a two-dimensional
representation of its recurrences where the value of a specific pixel is 1 if the
distance between the two corresponding trajectory points is less than a threshold
value epsilon. Important measures calculated are: Recurrence Rate (RR),
%Determinism, Divergence, Shannon Entropy, LMean, and Renyi entropy (K2). Time
Resolved RQA: By implementing a sliding window design, each of the above
calculated parameters is computed multiple times. Alignment of those parameters
with the time series reveals details not obvious in the 1 -dimensional time
series data. The breathing pattern for seven randomly chosen volunteers were
recorded using the RPM system for 15 minutes. Non-linear prediction was performed
and the normalized root mean square error (NRMSE) was calculated for each of the
volunteer data. RESULTS: The threshold value epsilon was chosen such that the
Recurrence Rate was equal to 1%. There is a strong correlation of NRMSE with
Entropy, Determinism and LMean. Time resolved RR locates strong Unstable Periodic
Orbits(UPOs), i.e. patterns of uninterrupted equally spaced diagonal lines.
CONCLUSIONS: RQAs could prove to be a very powerful tool for design of
personalized treatment regimen. Entropy, Determinism in conjunction with strong
UPOs can be used to determine if patients are suitable candidates for prediction
and chaos control.
PMID- 28518906
TI - SU-E-J-153: Volumetric and Dosimetric Variations of Post-Prostatectomy Patients
Treated with Radiation Therapy and Endorectal Ballon.
AB - PURPOSE: Post-prostatectomy patients may be treated with endorectal balloon (ERB)
placed during the radiation therapy. The objectives of this tudy are to
investigate geometrical variation of organs at risk (OAR) and CTVs (based on RTOG
and EORTC guidelines) throughout the course of radiation therapy and their
dosimetric impact. METHODS: Six consecutive post-prostatectomy patients enrolled
on a prospective IRB approved institutional study were analyzed. Patients
underwent CT/MRI simulation and treatment with daily endorectal balloon (ERB).
Six T2-MRI scans were performed during the treatment course. Bladder, rectum and
two sets of CTVs according to the RTOG and EORTC guidelines were contoured by
physician on each of the weekly MRI scans. The MRI scans were subsequently
rigidly fused to the CT simulation images to simulate daily kV-kV patient
alignment. RESULTS: 1. A consistent trend of decreasing bladder volume was found
after the first week of treatment and therefore the V65Gy was found to increase
after the second week of the treatment.2. The rectal volume with ERB was found to
be relatively consistent during the treatment course. Displacements of rectal
contours were within 2mm in all directions. The V60Gy<20% (our institutional
rectal constraint) varied on average less than 2%.3. We found that the CTV
volumes contoured per EORTC guideline exhibits a larger variation than those
drawn according to the RTOG guidelines most likely due to the bladder exclusion
imposed by it. While the average variation of RTOG based CTV volume was found
within 5%, the variation of CTV-EROTC volumes was more then 10%) (p = 0.06).
CONCLUSIONS: In post-prostatectomy patients undergoing radiotherapy with daily
ERB had a consistent decrease in the bladder volume during the treatment leading
to increased bladder irradiation and changes in the CTV volumes predominantly
when EORTC guideline were followed.
PMID- 28518907
TI - SU-E-J-126: Generation of Fluoroscopic 3D Images Using Single X-Ray Projections
on Realistic Modified XCAT Phantom Data.
AB - PURPOSE: To simulate the process of generating fluoroscopic 3D treatment images
from 4DCT and measured 2D x-ray projections using a realistic modified XCAT
phantom based on measured patient 3D tumor trajectories. METHODS: First, the
existing XCAT phantom is adapted to incorporate measured patient lung tumor
trajectories. Realistic diaphragm and chest wall motion are automatically
generated based on input tumor motion and position, producing synchronized,
realistic motion in the phantom. Based on 4DCT generated with the XCAT phantom,
we derive patient-specific motion models that are used to generate 3D
fluoroscopic images. Patient-specific models are created in two steps: first, the
displacement vector fields (DVFs) are obtained through deformable image
registration of each phase of 4DCT with respect to a reference image (typically
peak-exhale). Each phase is registered to the reference image to obtain (n-1)
DVFs. Second, the most salient characteristics in the DVFs are captured in a
compact representation through principal component analysis (PCA). Since PCA is a
linear decomposition method, all the DVFs can be represented as linear
combinations of eigenvectors. Fluoroscopic 3D images are obtained using the
projection image to determine optimal weights for the eigenvectors. These weights
are determined through iterative optimization of a cost function relating the
projection image to the 3D image via the PCA lung motion model and a projection
operator. Constructing fluoroscopic 3D images is thus reduced to finding optimal
weights for the eigenvectors. RESULTS: Fluoroscopic 3D treatment images were
generated using the modified XCAT phantom. The average relative error of the
reconstructed image over 30 sec is 0.0457 HU and the standard deviation is
0.0063. CONCLUSIONS: The XCAT phantom was modified to produce realistic images by
incorporating patient tumor trajectories. The modified XCAT phantom can be used
to simulate the process of generating fluoroscopic 3D treatment images from 4DCT
and 2D x-ray projections.
PMID- 28518908
TI - SU-E-J-137: A Theoretical Model for the Analysis of Residual Motion Artifacts in
4D CT Scans.
AB - PURPOSE: The purpose of this study was to analysis the residual motion artifact
in 4D-CT scan using a simple one-dimension theoretical model. METHODS: In order
to evaluate the target displacement at each phase image, We used phantom (Dynamic
Thorax Phantom, CIRS, Norfolk, VA) which could control programmable regular 1D
sine motion and belt type respiratory monitoring system. 2cm diameter spherical
target was inserted in the phantom and then we set-up regular 1D sine motion and
adjusted three level of amplitude (10, 20, 30 mm) with fixed period (4s). Four
dimensional (4D) CT images were acquired by CT scanner (Sensation Open, Siemens
Medical Systems, Forchheim, Germany) with a slice thickness of 1.5 mm and 0.1
pitch in helical mode. Respiratory monitoring system (AZ-733V, Anzai MEDICAL) was
placed on the abdominal surface of phantom, and the respiratory signal was
acquired. CorePLAN (RTP, SC&J) software was used to acquire static target
diameter and each ten phase diameters. RESULTS: The displacements (?S) peak at
the 20~30% or 70~80% phases, and are minimized at the 50% phase. This is because
the target velocity is minimum at 50% phase and maximum at 30 and 70% phases;
hence, the large image blur. The measured diameters of target are compared to the
simulation results and we observed similar trends of target diameter change.
CONCLUSIONS: In this study, we presented simple one-dimensional model to analyze
the residual motion artifact in 4D-CT scan. The model was used to explain the
effect of residual motion on each phase target displacement and also shown that
residual motion artifact was affected that the target velocity at each phase.
Lastly based on this model, we developed simulation program and acquired similar
results of target displacement compared with measured data. This research was
supported by Leading Foreign Re-search Institute Recruitment Program through the
National Research Foundation of Korea (NFR) (Grant No. K20901000001-09E0100
00110,) and the program of Basic Atomic Energy Research Institute (BAERI) which
is a part of the Nuclear R and D Programs (No.20110006324) funded by the Ministry
of Education, Science and Technol-ogy(MEST).
PMID- 28518909
TI - SU-E-J-147: Dosimetric Consequences of Intrafraction Prostate Motion: Comparison
Between Phantom Measurements and Three Different Calculation Methods.
AB - PURPOSE: Evaluation of different calculation methods for dose modification due to
intrafraction prostate motion using film measurements as ground truth. METHODS:
We acquired intrafraction motion data with the Calypso tumor tracking system by
Varian Medical Systems Inc for 4 prostate IMRT patients treated with 35 fractions
each. These motion data were transferred to a phantom platform which reproduces
the observed motion and has a 20 cm diameter cylindrical solid water phantom
mounted. For each patient all fractions were irradiated on one radiochromic MD-V2
55 film placed in the isocentric transversal slice of this phantom. These films
serve as ground truth for three calculation Methods: 1) Recalculation of the plan
with shifted target point for every segment with the segment's mean Calypso
position. 2)+3) Convolution of the static dose distribution with a probability
density function of the observed positions. For 2) only Calypso positions with
activated beam on signal were used whereas for 3) all Calypso positions between
the first and the last beam on signal for all fractions were employed. The
comparisons between films and calculated dose distributions were made with the
verification software VeriSoft 3.2 (PTW, Freiburg, Germany) where an 8*8 cm2 ROI
around the isocenter was selected for gamma evaluation. RESULTS: The segment
shifted plans reach 3%/3mm gamma values above 90% against the films for all four
patients. For both convolution methods three values are above 90%, only for the
patient with the largest intrafraction motion they decrease to 89%. CONCLUSIONS:
Shifting of the target point for every segment is well suited to estimate the
dosimetric consequences of intrafraction prostate motion. This may facilitate the
evaluation of different margin sizes or dose prescribing recipes under different
motion conditions. If such a lengthy calculation is not possible, a convolution
with motion data can be used for acceptable results, too. Our work was partially
supported by Siemens Healthcare and Varian Medical Systems Inc.
PMID- 28518910
TI - SU-E-J-157: Simulation and Design of a Real-Time 6D Head Motion Compensation
Platform Based on a Stewart Platform Approach.
AB - PURPOSE: Real-time sub-millimeter head motion compensation during frameless SRS
delivery has the potential to achieve the accuracy of frame-based SRS while being
significantly less invasive. Previously, we demonstrated real-time 6D head motion
monitoring using an optical camera, however, at the time we were limited to only
3D (x-y-z) of head motion correction due to mechanical restrictions of the head
platform. In this work we investigate the feasibility of using a compact 6D
robotic Stewart platform (hexapod) placed under the patient's head to perform
both translational and rotational motion compensation in real-time. Benefits of a
hexapod approach over a conventional serial kinematics stage include less flex,
compactness, high force to weight ratio, and fast response times. METHODS: A
hexapod is a parallel robotics device consisting of two platforms connected by
six linear actuators oriented at particular angles. To provide accurate motion in
6D, the desired position of the top platform (head) was ascertained using inverse
kinematics. MATLAB was used to simulate the six actuator positions for performing
motion along x-y-z-phi -theta-psi. Prior recorded 6D human volunteer head motion
data was used as an input for simulation of motion compensation. Six Firgelli L12
P linearservo actuators, together with a PCI-7344 motion controller and Labview
software, were used for initial construction of a hexapod prototype. RESULTS: The
necessary actuator lengths over time were computed for this data, simulating the
required 6D movement of the hexapod for motion correction. Simulations on
previously collected volunteer data indicate a hexapod system is capable of
responding to subject head motion with corrections of precise movements, and
solutions to the linear system can be computed at near real-time speeds.
CONCLUSIONS: Based on simulated results, it was successfully demonstrated that a
hexapod device can compensate for small patient head motions along all six
degrees of freedom.
PMID- 28518911
TI - SU-E-J-130: Study of the Image Quality Degradation in Phase-Based 4DCT Imaging
for Radiation Oncology.
AB - PURPOSE: Four-dimensional computed tomography (4DCT) integrated into radiation
imaging system is a useful tool for accurate targeting. 4DCT has the ability to
minimize breathing related artefacts compared to conventional CT but irregular
breathing and large tumour motion may cause inappropriate reconstruction. Our aim
is to estimate the image quality degradation of 4DCT and to assess the clinical
consequences. METHODS: The performance of the respiratory gating system of the
multi-slice CT-simulator Brilliance Big Bore was evaluated employing one
dimensional moving phantom. The binning algorithm was phased-based. 4DCT scans of
the test-phantom were acquired applying periodic motion patterns characterized by
amplitude and frequency spanning a clinically range and also irregular waveforms
simulating realistic breathing cycles. The internal spherical objects of the
moving phantom were contoured using semiautomatic segmentation for evaluating
uncertainties in volume delineation and motion amplitude calculation. Motion
amplitude was determined by a specially written MATLAB program. Afterwards we
investigated the influence of the image distortions on the targeting and the
consequences of the related uncertainties on the calculated dose distribution of
the tumour and the lungs in a group of five lung-cancer patients. RESULTS: The
results obtained with the phantom show that 4DCT imaging is still affected by
distortions due to residual motion. The inaccuracies are mainly related to the
amplitude (R2=0.99, R2=0.97 for 20 mm-dia sphere and 10 mm-dia sphere,
respectively) and to the oscillation frequency (R2=0.87 for 20 mm-dia sphere,
R2=0.96 for 10 mm-dia sphere) of simulated respiratory cycle and can cause both
underestimation and overestimation of the real tumour motion amplitude with an
average difference between real and calculated amplitude of about 10%.
CONCLUSIONS: The resulting inaccuracies on the internal tumour volume delineated
do not have significant clinical consequences on lung doses but they could be
important on tumour dose distribution if they imply underestimation of the real
tumour motion.
PMID- 28518912
TI - SU-E-J-163: Video-Based Patient Motion Detection during the Treatment Delivery.
AB - PURPOSE: During the treatment, a patient is continuously monitored by video
cameras. The therapists are supposedly to watch the monitors and interrupt the
treatment if any significant patient motion is spotted. Unfortunately, patient
motion can easily be overlooked with this manual approach, especially when there
are many other monitors in the control console area. Motion detection algorithms
can help to prevent this situation by alerting therapists if a significant motion
is detected. METHODS: We propose a method based on matrix decomposition into low
rank and sparse matrices to separate background and moving objects from a video
camera. The matrix is formed with image frames of the video and after
decomposition, the low rank component represents the background and the sparse
component is used to identify moving subjects in the video. The matrix
decomposition is performed by solving a convex optimization problem via an
efficient alternating direction method. Combining prior knowledge about the
motion of treatment machines, our method can reliably extract the actual patient
motion from the machine motion and background changes. RESULTS: We tested the
algorithm using videos obtained from a volunteer lying on the treatment couch
under the linac. We managed to isolate the patient and treatment machine motions
from the background. CONCLUSION: Our algorithm can separate the patient motion
from the background and therefore makes it possible to efficiently detect when
this motion is above a certain threshold. This method requires that a large
number of frames are acquired, but the concept can be extended to real time by
adaptively update the low rank component.
PMID- 28518914
TI - SU-E-J-173: Can a Metal Artifact Reduction Algorithm Affect Accuracy of Dose
Calculation?
AB - PURPOSE: In external beam radiotherapy, the presence of metal implants such as
hip prostheses causes significant streak artifacts in planning images, thus
affecting the accuracy of target and critical organ delineation. The purpose of
this study is to evaluate the improvement of image quality and impact on accuracy
of dose calculation by using a commercially available metal artifact reduction
(MAR) algorithm. METHODS: Nine patients were selected for this study, including 5
patients with unilateral hip prostheses for orthopedic irradiation, and 4
patients with unilateral or bilateral hip prostheses for prostate cancer
treatment. For each patient, simulation CT image was reconstructed with and
without MAR correction. Contours of the prostate, bladder and rectum were
delineated on both images by an experienced physician for the prostate patients.
The difference of contours between MAR corrected and un-corrected images was
quantified by an overlap index, and dose calculation accuracy was evaluated for
both target and critical organs. RESULTS: For orthopedic patients, dose
difference between MAR corrected and un-corrected images was negligible: 0.1+/
0.1% for maximum dose and 0.8+/-1.8% for dose at isocenter. For prostate
patients, no significant dosimetric difference was observed between MAR corrected
and un-corrected images if same contours were used in the treatment planning. For
the PTV, the average dose variation in D99 was 0.9+/-0.6%. The dose differences
in D50 of the bladder and rectum were 1.0+/-0.8% and 0.4+/-0.3%, respectively.
The average overlap index of prostate between the two images was 0.86+/-0.12 for
patients with bilateral hip replacements. Substantial changes in the dose-volume
histograms were observed if different contours were used in the treatment
planning. CONCLUSIONS: The commercial MAR algorithm can improve the image quality
dramatically and the MAR corrected images do not affect dose calculation
accuracy. The improvement of accuracy in organ delineation provides significant
dosimetric advantage. Philips Healthcare.
PMID- 28518913
TI - SU-E-J-141: Assessment of the Magnitude and Impact of Trigger Delay in
Respiratory Triggered Real-Time Imaging during Radiotherapy.
AB - PURPOSE: To assess the trigger delay in respiratory triggered real-time imaging
and its impact on image guided radiotherapy (IGRT) with Varian TrueBeam System.
METHODS: A sinusoidal motion phantom with 2cm motion amplitude was used. The
trigger delay was determined directly with video image, and indirectly by the
distance between expected and actual triggering phantom positions. For the direct
method, a fluorescent screen was placed on the phantom to visualize the x-ray.
The motion of the screen was recorded at 60 frames/second. The number of frames
between the time when the phantom reached expected triggering position and the
time when the screen was illuminated by the x-ray was used to determine the
trigger delay. In the indirect method, triggered kV x-ray images were acquired in
real-time during 'treatment' with triggers set at 25% and 75% respiratory phases
where the phantom moved at the maximum speed. 39-40 triggered images were
acquired continuously in each series. The distance between the expected and
actual triggering points, d, was measured on the images to determine the delay
time t by d=Asin(wt), where w=2pi/T, T=period and A=amplitude. Motion periods of
2s and 4s were used in the measurement. RESULTS: The trigger delay time
determined with direct video imaging was 125ms (7.5 video frames). The average
distance between the expected and actual triggering positions determined by the
indirect method was 3.93+/-0.74mm for T=4s and 7.02+/-1.25mm for T=2s, yielding
mean trigger delay times of 126+/-24ms and 120+/-22ms, respectively. Although the
mean over-travel distance is significant at 25% and 75% phases, clinically, the
target over-travel resulted from the trigger delay at the end of expiration (50%
phase) is negligibly small(< 0.5mm). CONCLUSIONS: The trigger delay in
respiration-triggered imaging is in the range of 120-126ms. This delay has
negligible clinical effect on gated IGRT.
PMID- 28518915
TI - SU-E-J-151: Evaluation of a Real Time Tumour Autocontouring Algorithm Using In
Vivo Lung MR Images with Various Contrast to Noise Ratios.
AB - PURPOSE: To quantitatively evaluate a lung tumour autocontouring algorithm using
in-vivo lung cancer patient MR images with varying contrast to noise ratios (CNR)
simulating images acquired at various MR field strengths. METHODS: A non small
cell lung cancer patient with posterior lung tumour is imaged (sagittal plane) in
a 3T MRI using a dynamic bSSFP sequence (FOV: 40*40cm2 , voxel size:
3.1*3.1*20mm3 , TE = 1.1ms. TR = 2.2ms, 275ms per image) under free breathing for
approximately 3 minutes (650 images). Gaussian random noise is added to the 3T
images to approximately simulate the equivalent CNR in images acquired at 1.5T,
1.0T, 0.5T, 0.3T and 0.2T. The moving tumour in all 3T images is contoured by a
physician for reference. The first 20 of these manual contours are used for the
parameters optimization of auto-contouring algorithm. The automatic contours from
the remaining images are quantitatively compared with the physician's contours
using the centroid's displacement and the Dice's coefficient (DC). RESULTS: The
oncologist's contours of the 3T images show a maximum S-I motion of 26mm.
Compared to the oncologist's contours, automatic contours have an average
centroid displacement of 1.37mm, and an average DC of 0.881. The autocontouring
algorithm's performance with images in the range of 1.5T to 0.5T equivalent CNRs
is similar to that of the 3T data. However, for the lowest CNR datasets (0.2,
0.3T) an increase in centroid displacement and decrease in DC is observed, with
mean displacements of 1.56mm, 1.71mm and DCs of 0.870, 0.836 for the 0.3T and
0.2T dataset, respectivelyConclusions: With in-vivo MR images, the autocontouring
algorithm generated lung tumour contours similar to ones drawn by a physician (DC
> 0.83). In this patient, additional CNR from >0.5T MRIs does not provide
statistically significant improvement in the accuracy of our autocontouring
software. E.Yip is supported by the Canadian Institutes of Health Research as
well as Alberta Innovates - Health Solutions.
PMID- 28518916
TI - SU-E-J-123: Blinded Clinician Evaluation of Amplitude versus Phase Binned 4DCT
Patient Data.
AB - PURPOSE: The purpose of this study is to evaluate the clinician's perspective of
amplitude versus phase-based binning of four-dimensional computed tomography
(4DCT). METHODS: Ten random lung cancer patients were selected with 10-phase
binned 4DCT's acquired on a Philips BigBore (Philips Healthcare, Andover, MA).
The data was re-binned using the amplitude of the respiratory signal and a new 10
phase 4DCT dataset was generated. These two datasets were coregistered and shown
together for each patient in cine mode in MIMVista (MIM Software, Cleveland, OH).
Nine clinicians were shown the images and asked to determine if one dataset was
more clinically beneficial or if there was no difference. The clinicians were
blinded to the nature of each dataset and to each other's' responses. The data
were tabulated using a point system where each patient was given +1 point if the
amplitude binned image was selected, -1 point if the phase binned image was
selected, and 0 points if they looked the same. RESULTS: The results showed large
variations from patient to patient. Scores ranged from -7 to 9 with a mean score
of -0.7 indicating a very small preference toward the phase-binned datasets. For
one patient, all of the clinicians selected the amplitude binned dataset. For two
patients, no clinicians selected the amplitude binned dataset. The mean
percentage of responses per patient that favored the amplitude binned dataset was
27.8% and the phase-binned dataset was 35.6%. No difference was detected in 36.7%
of responses. CONCLUSIONS: It is not clear from our limited data that clinicians
prefer amplitude or phase binned datasets for a random selection of lung cancer
patients. This suggests that patients could benefit on a case-by-case basis
depending on breathing pattern.
PMID- 28518917
TI - SU-E-J-161: Biomechanical Framework for Thoracic Tumors Characteristics.
AB - PURPOSE: Respiration-induced kinematics of thoracic tumors suggests a simple
analogy with elasticity, where a strain is used to characterize the volume of
interests. The application of the biomechanical framework allows for the
objective determination of tumor characteristics. METHODS: The deformation of a
given tissue element can be determined if its displacement is known. The latter
can be obtained from 4DCT scans using image registration of the end of inhalation
and exhalation CT volumes. The averaged right Cauchy-Green strain tensor was
determined for each of the 15 retrospectively analyzed thoracic GTVs. The
departure of the strain tensor from the identity matrix gauges the departure of
the medium from rigidity. The averaging was carried out in Log-Euclidean
framework. The fractional and geodesic anisotropy factors were determined for the
tensor. RESULTS: The amplitude of GTV motion varied from 0.64 to 4.21 with the
average of 1.2cm. The GTV size ranged from 5.16 to 149.99cc with the average of
43.19cc. The tumor deformation is inconsiderable and the tensorial anisotropy is
small. The Log-Euclidean distance of averaged strain tensors from the identity
matrix ranged from 0.06 to 0.31 with the average of 0.19. The Frobenius distance
from the identity matrix is similar and ranged from 0.06 to 0.35 with the average
of 0.21. Their fractional anisotropy ranged from 0.02 to 0.12 with the average of
0.07. Their geodesic anisotropy ranged from 0.03 to 0.16 with the average of
0.09. These values also indicate insignificant deformation. CONCLUSION: The
biomechanical framework allows for the quantitative description of the tissue or
anatomical regions of interest. Such regional characterization of volume of
interests can be used in the objective evaluation of changes of the anatomy
during the treatment or after the treatment. It might be used for correlation of
outcome studies with objective characterization of changes within biomechanical
framework. These objective characteristics do not rely on human interpretation.
The measured changes might have predictive characteristics for the therapeutic
success of the treatment.
PMID- 28518918
TI - SU-E-J-166: Development of Real-Time Motion Verification System for Respiratory
Gated Radiotherapy.
AB - PURPOSE: To develop an on-line quality assurance tool for RPM (real-time position
management system, Varian Medical Systems, Palo Alto, CA) phase-based gated
radiotherapy. METHODS: A real-time motion verification system (RMVS) was
developed to verify the positional reproducibility of patient breathing between
CT simulation and treatment. Phase-resolved anterior body midlines were extracted
from the 4D-CT simulation data to constitute 4D reference lines. During the
treatment, multiple infrared reflective markers attached on patient's body
midline were tracked by a custom stereo camera system. The RPM-generated phase
value was delivered to RMVS via in-house network communication software. The real
time positions of tracked markers were simultaneously compared with the 4D
reference line dynamically selected according to the phase value. The technical
feasibility of the system was evaluated by simulating a motion phantom under
several scenarios such as ideal case (with identical motion parameters between
simulation and treatment; cycle = 3.1 s, baseline = 0.0 mm, amplitude = 31.0 mm),
cycle change, baseline shift, and amplitude change. RESULTS: The developed system
(i.e., RMVS) was fully compatible with RPM. In the phantom experiments, RMVS
detected 5.2 +/- 1.3, 4.7 +/- 1.2, and 9.8 +/- 1.2 mm mean absolute errors (MAE)
for -5.0, 5.0, and 10.0 mm baseline shifts, respectively. However, revealing
about 1.0 mm MAE for both ideal and cycle change scenarios, RMVS turned out to
have a systematic error. With 22.0, 26.0, 35.0, and 41.5 mm amplitudes, RMVS
detected 2.3 +/- 1.3, 1.5 +/- 1.1, 2.3 +/- 1.4, and 4.9 +/- 2.5 mm MAE,
respectively. CONCLUSIONS: The developed system demonstrated a competence for
phase-matching error detection between real-time patient's motion and 4D-CT-based
reference. Thus, it could be used as an on-line quality assurance tool for RPM
phase-based radiotherapy. This work was supported in part by the SNU Brain Fusion
Program Research Grant No. 400-20100049 (2010-2011) and the National Research
Foundation of Korea (NRF) grant (800-20110212) funded by the Korea government
(MEST).
PMID- 28518919
TI - SU-E-J-177: Characterization of the Effect of 'Lung Detail' CT Reconstruction
Algorithm on Radiation Therapy Dose Calculation.
AB - PURPOSE: Precise tumor delineation is important in thoracic radiation therapy
planning, and using a 'lung detail' computed tomography (CT) reconstruction
algorithm can assist in visualizing the tumor. We seek to determine the
dosimetric impact of utilizing a lung detail algorithm versus a standard
algorithm on calculated dose in radiation treatment planning. METHODS: Ten
patients, with 12 tumors, were analyzed in this study. Two CT scans, one
reconstructed using a standard algorithm and one using a lung detail algorithm,
were generated for each of 12 lung tumors. Treatment plans were calculated for
each CT scan, with 7 tumors receiving stereotactic ablative radiotherapy (SABR)
and 5 receiving intensity-modulated radiation therapy (IMRT). The Hounsfield unit
(HU) and dose values for each voxel of the planning tumor volume (PTV),
esophagus, spinal cord, and contralateral lung in both the CT and dose images
were exported to MATLAB. For each contour, the voxel-by-voxel differences in the
HU and dose distributions between the two scans were analyzed along with dose
volume histogram (DVH) data. RESULTS: Despite changes in HU values, the voxel-by
voxel analysis showed a negligible shift in dose values. The mean differences in
dose for PTV, esophagus, spinal cord, and contralateral lung ranged from -12.12
to 22.57, -2.21 to 7.40, -0.50 to 5.93, and -1.12 to 7.41 cGy, respectively. DVH
comparisons demonstrated no meaningful difference between plans. The mean PTV,
esophagus, spinal cord, and contralateral lung doses measured from the DVH
shifted between plans an average of 3.5, 2.93, -0.6 and -0.35 cGy, respectively.
These dose differences are all less than 1% of the dose prescribed to the tumor
and are not measurable by current technology. CONCLUSIONS: The lung detail
reconstruction algorithm, when applied to thoracic radiation treatment planning
CT scans, can help precisely delineate tumor with negligible dosimetric impact.
PMID- 28518920
TI - SU-E-J-170: Clinical Evaluation of Positioning Accuracy of Two Immobilization
Devices for Stereotactic Body Radiotherapy Using Cone Beam CT.
AB - PURPOSE: To evaluate the patient positioning accuracy and reproducibility of two
commercially available immobilization systems for Stereotactic Body Radiotherapy
(SBRT) treatment. METHODS: Forty one patients with lung (n=21) or liver (n=20)
malignancies were assigned to one of the two immobilization devices: Elekta
stereotactic body frame (SBF) with built-in stereotactic coordinate system and
Civco modular indexing based frame (MIF) without stereotactic reference. All
patients underwent the same simulation and planning procedure followed by cone
beam CT (CBCT) guided treatment setup. A total of 151 CBCT images were analyzed.
The systematic and random isocenter setup errors of the two systems were
calculated and compared based on the daily setup corrections under CBCT guidance.
RESULTS: There was not statistically significant difference between the two
systems in terms of systematic setup errors in all three translational
directions, for both lung and liver patients. The random errors for the lung
patients under SBF setup were 1.8mm, 2.0mm and 2.9mm for the vertical,
longitudinal and lateral directions, respectively compared to 3.6mm, 4.1mm, and
4.2mm for MIF. A similar trend was also observed for liver patients. The random
errors of liver MIF setup reached 3.5mm, 6.1mm and 5.7mm for the vertical,
longitudinal and lateral directions, respectively, with relatively smaller errors
1.7mm, 3.4mm and 2.6mm with SBF setup. Repeated CBCTs occurred for MIF system in
42.4% and 40.7% of the lung and liver treatment to verify couch corrections based
on the institutional tolerance, resulting in prolonged setup time. Only 25% and
13.6% of the lung and liver treatment with SBF required with repeated CBCT.
CONCLUSIONS: Without stereotactic coordinate reference, the body frame system
tended to have larger random setup errors and patient positioning accuracy
inevitably relies on the volumetric imaging guidance. Patient comfort and
reproducibility should be clearly considered for selecting a system.
PMID- 28518921
TI - SU-E-J-125: Uncertainty in Accumulated Dose to the Cochlea Due to Setup Error
during External Beam Treatment of Head & Neck Cancer Patients.
AB - PURPOSE: Treatment uncertainties are not included in modeling dose response of
hearing loss. We determine uncertainty of accumulated dose to cochleas of head &
neck cancer patients due to setup error during treatments of external beam IMRT.
METHODS: We studied 8 patients: 1 planning CT for each patient and total 40 cone
beam CTs. Those patients were treated with 33 fractions. Treatments delivered 70
Gy to PTV, 50 to 60 Gy to nodal and sub-clinical disease using IMRT dose
painting. Setup error was measured using 6-dimensional rigid registration between
planning CT and cone beam scans obtained prior to treatment. Planning CTs were
transformed and resliced to produce 'treatment CTs' according to the measured
setup error matrix to simulate the cochlea position during treatment. We
calculated dose delivered to cochleas at each treatment position. Treated dose to
the cochlea from each fraction was accumulated on the planning CT using its
registration with each 'treatment CT'. RESULTS: The RMS value of set error of
left cochlea is 0.48pm0.28cm, right cochlea is 0.47pm0.26cm. Mean values of left
and right cochleas are ~zero. Uncertainty in the dose to cochlea depends on each
treatment plan and relative positions of the cochlea and target volumes. Average
uncertainty of mean dose to cochlea is 5.0%, or 5.2cGy per fraction. CONCLUSION:
Patient setup error introduces uncertainty to the position of the cochlea and
consequent uncertainties in accumulated dose. Our method calculates accumulated
dose delivered to the same cochlea volume at different treatment positions due to
setup error. We found uncertainty in cochlea doses was 5% of planned dose after 4
to 7 fractions. The largest uncertainty was 17 cGy per fraction. Our Results will
be used to determine uncertainties in dose response of hearing loss in head and
neck patients. NIH R01-CA129182.
PMID- 28518922
TI - SU-E-J-136: Evaluation of a Non-Invasive Method on Lung Tumor Tracking.
AB - PURPOSE: to develop a non-invasive method to track lung motion in free-breathing
patients. METHODS: A free-breathing breathing model has been developed to use
tidal volume and air flow rate as surrogates for lung trajectories. In this
study, 4D CT data sets were acquired during simulation and were reconstructed
into 10 phases. Total lung capacities were calculated from the reconstructed
images. Continuous signals from the abdominal pneumatic belt were correlated to
the volumes and were therefore converted into a curve of tidal volumes. Air flow
rate were calculated as the first order derivative of the tidal volume curve.
Lung trajectories in the 10 reconstructed images were obtained using B-Spline
registration. Parameters of the free-breathing lung motion model were fit from
the tidal volumes, airflow rates and lung trajectories using the simulation data.
Patients were rescanned every week during the treatment. Prediction of lung
trajectories from the model were given and compared to the actual positions in
BEV. RESULTS: Trajectories of lung were predicted with residual error of 1.49mm
at 95th percentile of all tracked points. Tracking was stable and reproducible
over two weeks. CONCLUSION: Non-invasive tumor tracking based on a free-breathing
lung motion model is feasible and stable over weeks.
PMID- 28518924
TI - SU-E-J-129: Target-Specific Optimization of Four-Dimensional Cone Beam Computed
Tomography.
AB - PURPOSE: Undersampling artifacts are a major problem in four-dimensional cone
beam computed tomography (4D-CBCT) and may compromise evaluation of target
motion. The role of the target characteristics in scan parameter selection has
not been previously investigated. In this work, we evaluated 4D-CBCT performance
by assessing the accuracy of target motion measurements for various target sizes
and motions. The results may serve as patient-specific guidelines for selection
of scan parameters in 4D-CBCT. METHODS: We acquired 4D-CBCT scans of a moving
phantom consisting of six water-filled sphere targets of sizes 10 to 37 mm, with
various scan times ranging from 30 sec to 3 min. Two different (3-sec and 6-sec)
periods of motions were tested. We used automatic image registration to extract
the target motion trajectories and evaluated the accuracy of the measurement for
the various target sizes and motions for various combinations of scan parameters.
RESULTS: The most important object parameter to 4D-CBCT performance was the
period of motion. Measurements for the 6-sec motion were always systematically
less accurate than measurements for the 3-sec motion for 34 of 36 target
sizes/motions for any given scan time. For any given target size, a 45-sec scan
for the 3-sec motion yielded nearly equivalent accuracy to a 3-min scan for a 6
sec motion. The second most important parameter was the target size. A 1-min scan
was needed for sub-mm motion measurement accuracy of 28-mm target, whereas a 1.5
min scan was needed for the 22-mm target. For all sizes and motions, temporal
blurring was observed when the number of phases was fewer than 8. CONCLUSIONS:
Scan time should be set according to target size and motion. We have provided
figures that provide the minimum scan time needed to achieve the particular
motion measurement accuracy for a particular size and period of motion.
PMID- 28518923
TI - SU-E-J-156: Dosimetric Evaluation of Proper Width of Respiratory Gating Window
According to Dose Distribution of EBT2 Film.
AB - PURPOSE: We analyzed dose distribution depending on the width of gating window to
determine the proper width of gating window in gated radiation therapy. METHODS:
A three dimensional breathing simulator with house phantom was built to simulate
periodic sinusoidal breathing motion of 4 seconds/cycle and 3cm fan shape
movement. This was driven synchronized with Real-time Position Management (RPM)
system (Varian Medical Systems, Palo Alto, CA, USA), and thereafter 4D-CT images
were acquired. Three treatment fields (0 degrees , 120 degrees , 240 degrees )
with gating plan using treatment planning system (Eclipse, Varian, USA) were
performed aimed to be exposed 200cGy to isocenter. Dose evaluations regarding
static, non-gated motion, 60% (phase of 20%-80%), 40% (phase of 30%-70%), 30%
(phase of 40%-70%), 20% (phase of 40%-60%) and 15% (phase of 40%-55%) of gated
motion were carried out using EBT2 film, and extents of field size, high dose
exposed, penumbra were analyzed. RESULTS: In most cases, dose differences
compared to static were getting decreased as the width of gating window was
decreased. Non-gated motion showed -74.5% dose discrepancies compared to static
exposed, whereas 15% respiratory gating window showed within 1% dose difference.
Dose differences of 40% gating window was -30.7% whereas 30% gating window showed
-6.3% dose discrepancies. Dose difference was rapidly reduced from 30% gating
window against non-gated motion to 40% gating window in all cases of field size,
high dose area, and penumbra. CONCLUSIONS: 15% respiratory gating window was
regarded the most ideal width of gating window, but it will significantly
increase beam delivery time over a conventional treatment. Therefore, considering
beam delivery time and dose distributions of high dose area, field size, and
penumbra, 30% respiratory gating window would be recommended. This work was
supported by Nuclear Research & Development Program of the National Research
Foundation of Korea (NRF) grant funded by the Korean government (MEST).
PMID- 28518925
TI - SU-E-J-162: Development and Application of Internal and External Motion Tracking
System.
AB - PURPOSE: In this study, we performed the experiment of correlation between
internal organ movement and external abdominal surface movement for the mini pig
using the developed motion tracking system. METHODS: The experimental system was
consisted with imaging acquisition part and image signal analyzing part. The
image acquisition of internal organ was performed with a C-arm fluoroscopy
system, and abdominal surface images were acquired with a camera and image
acquisition board. The signal processing of the image was conducted using LabVIEW
8.6. The developed system was applied to a mini pig. The information of the
internal organ movement was acquired with C-arm fluoroscopy system by tracking
the fiducial gold maker pre-implemented into diaphragm, which was used in
Cyberknife radiation therapy. The data acquisition of internal organ movement due
to respiration and abdominal surface movement was performed under general
anesthesia. RESULTS: The motions of the internal and external markers were well
correlated. The correlation coefficients between the AP movement of the external
marker and the SI and RL movement of the internal target in the experiment using
the mini pig were resulted in 0.903 and 0.905, respectively. CONCLUSIONS: It is
confirmed that high correlations between the movements of external marker and the
targetassigned in diaphragm in the experimental case for the mini pig were
existed. Therefore, it is possible to predict the locations of internal target
from the movement of the external marker. These results show the possibility to
use the DTTRT (Dynamic Tumor Tracking Radiation Therapy) system of Korea
Institute of Radiological and Medical Science (KIRAMS) to clinical application of
animals.
PMID- 28518926
TI - SU-E-J-140: Initial Clinical Assessment of a Gimbaled Linac Tumor Tracking System
in a Patient Simulation Study.
AB - PURPOSE: A simulation study was conducted on patients to evaluate the workflow
and quantify the performance of the BrainLab/MHI Vero dynamic tumor tracking
system in clinical circumstances. METHODS: The gimbals hold the linac-MLC
assembly which enables tracking of moving tumors. Two kV imaging systems are
attached at +/-45 degrees from the 6MV beam allowing simultaneous X-rays. A
simulation study was conducted on 5 lung-liver patients. The procedure involved
quantification of tumor motion based on localization of Visicoil gold markers
implanted in the tumor. Except for switching on the treatment beam, the entire
tumor tracking workflow was executed involving patient positioning, synchronized
acquisition of skin marker motion and X-ray images, fiducial marker detection,
external-internal correlation model calculation, skin marker surrogate guided
tracking and monitoring imaging. Tracking error was calculated from gimbals log
files and the acquired monitoring X-rays. Imaging dose was measured with TLD on
phantoms and on the patients. RESULTS: Imaging for correlation model building
resulted in 17.6mGy skin dose. Taking the treatment duration of a 3*20Gy lung
SBRT treatment, depending on the treatment fields orientation an additional
maximal exposure of 28.8mGy was estimated for acquiring 1Hz X-ray monitoring
during tracking. A mean absolute tracking error of 1.1 mm was measured, with a
90% percentile of 2.1 mm. The average time to set up the patient entering the
room to the first MV beam-on was 9min. From the acquisition of the modeling
images sequence up to beam-on took 3min. CONCLUSIONS: A clinical version of the
Vero tumor tracking system has been installed, including automatic detection of
fiducial markers implanted in the tumor. An initial assessment has shown that the
tracking system is functional and its performance adequate to move forward to
final commissioning and initiation of patient treatments. This collaborative work
was supported by the Flemish government through the Hercules foundation and the
a?oeFonds voor Wetenschappelijk Onderzoek - Vlaanderena? grants G.0486.06 and
G.0412.08, and corporate funding from BrainLab AG. There are no other conflicts
of interest.
PMID- 28518927
TI - SU-E-J-172: Development of a Video Guided Real-Time Patient Motion Monitoring
System for Helical Tomotherpay.
AB - PURPOSE: We developed a video image-guided real-time patient motion monitoring
system for helical Tomotherapy (VGRPM-Tomo), and its clinical utility was
evaluated using a motion phantom. METHODS: The VGRPM-Tomo consisted of three
components: an image acquisition device consisting of two PC-cams, a main control
computer with a radiation signal controller and warning system, and patient
motion analysis software, which was developed in house. The system was designed
for synchronization with a beam on/off trigger signal to limit operation during
treatment time only and to enable system automation. In order to detect the
patient motion while the couch is moving into the gantry, a reference image,
which continuously updated its background by exponential weighting filter (EWF),
is compared with subsequent live images using the real-time frame difference
based analysis software. When the error range exceeds the set criteria
(delta_movement) due to patient movement, a warning message is generated in the
form of light and sound. The described procedure repeats automatically for each
patient. A motion phantom, which operates by moving a distance of 0.1, 0.2, 0.5,
and 1.0 cm for 1 and 2 sec, respectively, was used to evaluate the system
performance at maximum couch speed (0.196 cm/sec) in a Helical Tomotherapy (HD,
Hi-art, Tomotherapy, USA). We measured the optimal EWF factor (a) and
delta_movement, which is the minimum distance that can be detected with this
system, and the response time of the whole system. RESULTS: The optimal a for
clinical use ranged from 0.85 to 0.9. The system was able to detect phantom
motion as small as 0.2 cm with tight delta_movement, 0.1% total number of pixels
in the reference image. The measured response time of the whole system was 0.1
sec. CONCLUSIONS: The VGRPM-tomo can contribute to reduction of treatment error
caused by the motion of patients and increase the accuracy of treatment dose
delivery in HD. This work was supported by the Technology Innovation Program,
10040362, Development of an integrated management solution for radiation therapy
funded by the Ministry of Knowledge Economy (MKE, Korea). This idea is protected
by a Korean patent (patent no. 10-1007367).
PMID- 28518928
TI - SU-E-J-150: To Design a Methodology Based on Numerical Phantom for Reconstruction
of Dose Delivered to Moving Lung Tumors.
AB - PURPOSE: To design a methodology based on numerical phantom for reconstruction of
dose delivered to moving lung tumors. METHODS: MatlabTM 7.6 was used to generate
a 4D numerical lung phantom (NLP). Customer parameter files were used as input to
this NLP, which consists of multiple ellipsoids representing body, lung, cord and
tumor. In this study, we studied the impact of varying breathing pattern on a
left lower lobe tumor, where the tumor motion was simulated on the daily
breathing pattern of the patient acquired using real time positioning management
(RPMTM) system from Varian Medical Systems. Based on the daily breathing pattern,
the original RPM signal and the original tumor trajectory, 5 sets of motion
trajectories were simulated. This was then used to build 10 different phases of
the numerical phantom. Average Intensity Projection (AIP) was then generated from
the different phases. The actual delivered dose on the 5 AIP sets were compared
to the intended dose on the original planning AIP image set. RESULTS: The mean
target coverage (TC) recomputed on the 5 AIP sets was approximately 18% lower
than the TC for the planning AIP image set. The mean homogeneity index (HI)
recomputed on the 5 sets, was approximately 5 times higher than HI for the
planning AIP image set. The lung NTDmean dose was approximately 9.5 Gy3 and did
not differ much. CONCLUSIONS: The presented numerical simulation framework may
assist in monitoring the changes in dose accumulation due to changes in the
patient's breathing on a daily basis. This can also be used for validation of new
motion tracking algorithms and its impact of dose coverage.
PMID- 28518929
TI - SU-E-J-122: Quantification of Respiratory-Induced Pancreatic Head Tumor Rotation
and Deformation Using 4DCT and Fiducial Markers.
AB - PURPOSE: To quantify pancreatic head tumor rotation and deformation due to the
respiration using 4DCT and fiducial markers. METHODS: This study included
seventeen pancreatic head tumor patients who were treated with gated SBRT using
Novalis system in our institution. Each patient had two 5-mm-long fiducial
markers placed in pancreatic head approximately 2 cm apart for the gating
treatment. All patients had 4DCT scans of 3mm-slice thickness using a CT scanner
(SENSATION, SIEMENS) under free breathing condition to create the internal target
volume (ITV). The respiratory curve was generated through a pressure sensor
placed on the patient's abdomen. The 4DCT image data sets were binned into 8
phases: 0% inhale (end of exhale), 25% inhale, 50% inhale, 75% inhale, 100%
inhale (end of inhale), 75% exhale, 50% exhale, and 25% exhale. The fiducial
markers were contoured on each phase of 4DCT images, and the 3D coordinates
(x,y,z) of centroid of the fiducial marker were recorded. The distance between
two markers was calculated for each phase, and its variation on eight phases
indicated the pancreatic head deformation. The orientation change of the two
markers on eight phases indicated the pancreatic head rotation. Student t-test
was performed for the statistical analysis. RESULTS: Pancreatic head rotation and
deformation were observed through the breathing cycle. The largest rotation and
deformation happened to the course from 0% inhale to 100% inahle. The rotation
was 8.0+/-6.2 degree ranging from 2 to 20 degree. The deformation was 2.0+/-2.4
mm ranging from 0 to 6.6 mm. Both were statistically significant with p<10-4 for
rotation and p=0.0033 for deformation. CONCLUSIONS: The 4DCT images showed
significant pancreatic head rotation and deformation due to respiration, and both
rotation and deformation were highly variable between patients. For patients
receiving SBRT with tight margin, rotation and deformation need to be considered,
and individualized margin may be necessary.
PMID- 28518930
TI - SU-E-J-160: 4D Dynamic Arc of Non-Modulated Variable-Dose-Rate Fields for Lung
SBRT: A Feasibility Study.
AB - PURPOSE: Conformal SBRT plans for Lung cancer with static gantry angles are ideal
candidates for applying motion tracking because of: (1) better dosimetric
conformity with reduced target margin and (2) easier and more faithful target
tracking without intensity modulation. This work is to demonstrate that by
delivering the target tracking during gantry rotation, we can significantly
improve delivery efficiency without negatively affecting plan quality. METHODS: A
lung SBRT plan with static beams was created using CT images of the reference
breathing phase. It is converted to an arc plan with variable dose rate followed
by the conversion to a 4D plan with the segment aperture morphing (SAM) method
(Gui 2010) with considerations of both target location and shape changes as
depicted by the 4D CT. Gantry angle ranges were determined from the clinical
monitor units, with the 22.2 MU/degree, which is chosen to maximize the dose
rate. All segments of the dynamic 4D plan were merged into a single arc with
variable dose rate. Each segment occupying 1/10 of the breathing period delivers
6.6 MUs at a dose rate of 1000 MU/min. Delivery time was measured and compared to
the planned. RESULTS: The dose distributions of the single phase 3D plan and the
arc 4D plan showed little difference. The delivered time for the 4D arc plan
agreed with the calculated time, and is almost the same as delivering the 3D plan
without target tracking. A 12 Gy treatment takes less than 2.5 min. CONCLUSIONS:
The feasibility of a novel 4D delivery method where a 3D SBRT plan is converted
into 4D arc delivery has been demonstrated. In addition to realizing the
conventional target tracking benefits, our method further improves delivery
efficiency, which is important for maintaining the geometric relationship between
the target motion and the breathing surrogate during treatment. This study is
supported by NIH_Grant_1R01CA133539-01 A2.
PMID- 28518931
TI - SU-E-J-133: Quantitative Measurement and Modeling of Target Volume Changes by
Respiratory Motion in CT and Cone-Beam CT.
AB - PURPOSE: Variations in the target volume and length in CT and cone-beam CT (CBCT)
imaging by respiratory motion were investigated for different motion amplitude
and frequency. A model that predicts the target volume dependence on motion
amplitude, frequency, target size, speed of CT and CBCT scanning was developed.
METHOD AND MATERIALS: Three target volumes of differing sizes were constructed of
tissue-equivalent gel material and embedded into artificial lung phantom.
Respiratory motion was mimicked by a mobile phantom at a respiration frequency of
15 cycles/min for eight different amplitudes of respiratory motion in the range 0
20 mm. Images obtained for CT and CBCT were contoured and the target volumes and
superior-inferior lengths were calculated. A mathematical model was developed to
quantify and reproduce observed variations in target volumes and lengths due to
motion artifacts. RESULTS: The measured volumes and lengths of the different
targets increased by blurring artifacts of respiratory motion in CBCT images
because of long scanning times (about 1 minute), which was found to enlarge
linearly with the respiratory motion amplitude. However, in CT, the target
volumes and lengths could increase or decrease by imaging depending on whether
the CT scanning was parallel or opposed to the moving phantom. The mathematical
model predicts very well the variation in target volumes imaged by CT and CBCT as
a function of motion amplitude, frequency, target size, speed of CT and CBCT
scanning Conclusion: The measurement and modeling of target volume and length
variations provided quantitative assessment of induced artifacts in CBCT and CT
imaging by respiratory motion. The modeling of imaging artifacts induced by
respiratory motion in CT and CBCT can be used to define accurately gross tumor
volumes and organs-at-risk which will be very useful for accurate treatment
planning, target localization, motion tracking and beam gating during dose
delivery.
PMID- 28518932
TI - SU-E-J-165: Development of a Low-Cost and Clinically Available Patient
Intrafraction Motion Monitoring System.
AB - PURPOSE: We have developed a flexible system in order to monitor the
intrafraction motion. The purpose of our study is to extend the monitoring system
to clinically available system with low cost. METHODS: Our system is composed of
a standard web camera with a low-cost and 8x magnitude telescope, a personal
computer with our in-house software and a specific marker box. The telescopic
lens was attached with the web camera to extend more effective distance of the
measurement in order to avoid patient's interference. The dynamic calibration
algorithm was developed to take into account patient's rotation during treatment
in order to measure the intrafraction motion more accurately. Tracking three
markers simultaneously based on a template matching technique using parallel CPU
computing was performed to measure the intrafraction motion with dynamic
calibration. To evaluate our new system, a respiratory motion QA phantom with 10
mm-amplitude was used in order to measure the amplitudes under the different
angles of web camera setting (0 to 50 degree, 5 degree step) using our system and
Varian Real-Time Position Management Respiratory Gating (Varian-RPM) System. The
results of our system were compared with the results of Varian-RPM System.
RESULTS: The result of the amplitudes measured by our system and Varian RPM
System are 10.2+/-0.3 mm and 10.3+/-0.1mm at the angle of 0 deg., respectively.
The values of both systems were within the tolerance value of AAPM Task group
142. The results of the amplitude of our system and Varian-RPM system were 10.2+/
0.3mm and 10.4+/-0.1mm, respectively, while the angle was changed. Under the
parallel CPU computing, the calculation time to measure the position of the
marker was about 50msec including the latency. CONCLUSIONS: Our proposed system
could have clinically acceptable accuracies. The system would be contributed
broadly to improve the treatment accuracy because of low-cost installation of it.
PMID- 28518933
TI - SU-E-J-176: Clinical Evaluations of a Novel Metal Artifact Reduction Technique
for Treatment Planning in Radiation Therapy.
AB - PURPOSE: To evaluate the effects of a CT on-board commercially available metal
artifact reduction (MAR) algorithm for the use in radiation therapy treatment
planning. METHODS: Phantom and clinical data were used for evaluation. A CIRS
electron density phantom (Model 062) was scanned with Philips Brilliance BigBore
16-slice CT simulator to establish ground truth for CT Hounsfield numbers.
Titanium hip prostheses were subsequently inserted into the phantom to mimic
single or double hip implants. The phantom were scanned, CT images were
reconstructed with and without MAR correction. Dose distributions for a 6X or an
18X beam were calculated using the three datasets and compared. CT Hounsfield
number and variations were evaluated on both MAR-corrected and uncorrected images
of ten clinical cases with hip implants. Dose distributions for three patients
based on MAR-corrected images were compared to those of the uncorrected datasets
with artifact regions density-overridden to 1.0g/cc. RESULTS: Metal artifacts
were reduced dramatically on MAR corrected images for all phantom and patient
cases. The phantom study indicated a remarkable improvement of Hounsfield number
accuracy with maximum percentage difference reduction of 45% compared to the
ground truth. CT number standard variations of the critical organs for the
clinical cases were reduced from 30% to 66.7%. The image geometries were not
affected by the MAR algorithm. Both critical structures and targets on clinical
cases went from invisible to clearly visible. For all examined phantom and
clinical cases, dosimetry difference was within 3% (mostly within 1% of the
target volume) of the prescription dose and was not clinical significant for dose
calculations based on different image datasets. CONCLUSIONS: The MAR algorithm
can be safely utilized in the radiation therapy treatment planning process with
remarkable improvements in CT number accuracy and structure conspicuity.
Dosimetry is not highly dependent on the datasets utilized for dose calculations.
PMID- 28518935
TI - SU-E-J-124: Assessment of Intrafraction and Interfraction Motion in Cranial SRT
Using Tomotherapy.
AB - PURPOSE: Stereotactic radiotherapy delivers large doses of radiation to small
volumes with steep dose gradients, and therefore requires accurate positioning
and near complete immobilization throughout the delivery of treatment. This work
assesses intra and interfraction patient motion for two immobilization devices
for patients treated on Tomotherapy. METHODS: The study set consisted of 60
patients undergoing treatment for brain metastases over 5 fractions on MVCT
imaged-guided Tomotherapy. Patients were immobilized using either the frameless
Aktina PinPoint system or thermoplastic mask with bite block. To assess
intrafraction motion, a scan was performed at the end of 2 treatment fractions.
All MVCT Tomotherapy images were registered to the original kVCT in Amira 5.2
using a quasi- newton, normalized mutual information affine transformation. To
assess the precision and accuracy of MVCT image acquisition, reconstruction and
offline Amira registration to kVCT, a phantom study was conducted. RESULTS: The
phantom study demonstrated that the total error (noise floor) of the measurements
and imaging/registration workflow was 0.11 +/- 0.09 mm. The Aktina frameless
immobilization device yielded an average displacement of 2.58 +/- 2.29 mm for
intrafraction patient motion and 2.54 +/- 1.37 mm for interfraction patient setup
differences, while mask immobilization yielded average intrafraction patient
motion of 1.29 +/- 1.18 mm and interfraction patient setup differences of 2.13 +/
1.49 mm. Finally, 95% of all intrafraction motion using mask immobilization fell
within our clinically used 2 mm margin, as compared to 75% of Aktina
immobilization over the same margin. A margin of 3.5 mm is necessary for Aktina
immobilized patients to include 95% of intrafraction motion within the margin.
CONCLUSIONS: Our data indicates that mask immobilization performed better at
preventing intrafraction motion and reducing interfraction patient setup
differences.
PMID- 28518934
TI - SU-E-J-169: 4D-PET for Abdominal Tumor Target Volume Generation.
AB - PURPOSE: To examine the impact of 4D-PET on target volume delineation of upper
abdominal tumors, versus conventional un-gated PET. METHODS: Four patients with
upper-abdominal tumors underwent respiratory-correlated FDG PET/CT scanning (4D
PET) as part of a continuing IRB-approved research protocol. Internal target
volumes of FDG-avid tumors were contoured on the 4D-PET and conventional un-gated
PET by a radiation oncologist who is a specialist in gastro-intestinal tumors. To
create the 4D-PET ITV, the end-inhale and end-exhale 4D-PET phases were used. The
relative volumes and volumetric overlaps of the 4D and un-gated target volumes
were examined. Additionally, 4D-PET was used to measure the motion of the tumors.
RESULTS: Of the four patients who were imaged, one showed minimal motion (< 3 mm
in any direction) and one showed minimal FDG avidity; these were removed from
further analysis. Of the two tumors which showed significant motion and FDG
uptake, 4D-PET volumes were 28% and 21% larger than un-gated PET volumes. The un
gated PET volumes were almost entirely contained within the 4D-PET volumes (95%
and 93% for the two tumors). Tumors appeared to deform as well as translate with
breathing, although this could be due to varying intra-gate motion rather than
actual physiological deformation. The superior-inferior borders of the tumors
exhibited the most motion, with displacements of 5.6 mm and 6.4 mm. CONCLUSIONS:
4D-PET can be used to estimate the motion of FDG-avid upper-abdominal tumors. Use
of 4D-PET increases the size of target volumes compared to un-gated PET in a
subset of upper-abdominal cancer patients. Direct measurement of tumor motion and
deformation by 4D-PET imaging could allow the use of patient-specific margins
rather than population-based margins, potentially leading to increased target
coverage and reduced normal tissue irradiation.
PMID- 28518936
TI - SU-E-J-135: 3-D Fourier-Based Volumetric Registration for Estimating Intra
Fractional Lung Tumor Motion.
AB - PURPOSE: To develop a three-dimensional (3-D) volumetric registration algorithm
to estimate the intra-fractional lung tumor motion between respiratory phases for
improving the accuracy of radiotherapy treatment. METHODS: The 3-D thoracic CT
volumes (512*512*160 voxels, with dimensions 0.97*0.97*2.5 mm3 ) in different
respiratory phases were acquired on a General Electric Optima T580 scanner in
cine mode. As a preprocess, a bicubic interpolation was used to interpolate the
original 3-D volumes along the cephalo-caudal axis to volumes of size 512*512*400
voxels, with dimensions 0.97*0.97*1 mm3 . In each respiratory phase, a sub-volume
covering the tumor was roughly specified manually. A 3-D phase correlation of two
sub-volumes was computed by using the 3-D inverse Fourier transformation of the
normalized cross power spectrum of two sub-volumes. The 3-D displacements along
three axes were estimated by finding the location of the highest peak in the 3-D
phase correlation. RESULTS: Experiments were conducted on an artificial 4-D CT
data set and three clinical 4-D CT data sets. Experimental results shown that the
proposed algorithm was capable of estimating the tumor motion between respiratory
phases with a high-accuracy (mean square error <1 mm). CONCLUSIONS: This work
extended the conventional image registration techniques from 2-D to 3-D for tumor
motion estimation. This work indicates a potential for significant accuracy
improvement in radiotherapy treatment planning. The high-accurate 3-D tumor
motion information provides a reliable basis for expanding a clinical target
volume (CTV) to a planning target volume (PTV) to incorporate the intra
fractional tumor motion.
PMID- 28518937
TI - SU-E-J-146: Time Series Prediction of Lung Cancer Patients' Breathing Pattern
Based on Nonlinear Dynamics.
AB - PURPOSE: Prediction methods for breathing patterns, which are crucial to deal
with system latency in treatments of moving lung tumors using state-space
methodologies based on non-linear dynamics are contrasted to linear predictive
methods. METHOD AND MATERIALS: In our previous work we established that breathing
patterns can be described as a 5-6 dimensional nonlinear, stationary and
deterministic system that exhibits sensitive dependence on initial conditions. In
this work, nonlinear prediction methods are used to predict the short-term
evolution of the respiratory system for 3 patients. Single step and N-point multi
step prediction are performed for sampling rates of 5Hz, 10Hz, and 30Hz. We
compare the employed nonlinear prediction methods with respect to prediction
accuracy to Infinite Impulse Response (IIR) prediction filters. The simplest form
of local prediction is finding similar segments of scalar time series data in a
higher dimensional embedding space. Hence, we predict the future value x(t)of N
time steps ahead by simply finding the average of nearest neighbor points to the
point x(t) in the past and using them to estimate x(t+N), yielding a local
average model (LAM). Local linear models (LLM) which are linear autoregressive
models that hold only for a region around the target point formed by the nearest
neighbor points is combined with a set of linear regularization techniques to
solve ill-posed regression problems are also implemented. RESULTS: For all
sampling frequencies, both single step and N-point multi step prediction results
obtained using LAM and LLM with regularization methods are better than IIR
prediction filters for the selected sample patients. CONCLUSIONS: The use of non
linear prediction methods for predicting the breathing pattern of lung cancer
patients may lead to improved, robust and accurate long-term prediction to
account for system latencies.
PMID- 28518938
TI - SU-E-J-155: Evaluate a Stepped TE Segmented EPI Sequence for 3D Dose Monitoring
Using Gel Dosimetry.
AB - PROBLEM: Gel based MR relaxometry provides accurate 3D dosimetric mapping. The
routinely used multi spin echo (MSE) sequence has limitations. Our aim was to
evaluate a stepped TE segmented EPI sequence for 3D dose monitoring at 1.5T and
3T. METHODS: The polymer gel (BANG KIT, MGS Research) was prepared under normoxic
conditions and stored in glass vials. Calibration was performed under dose range
of 3-18 Gy with irradiation using the True Beam. Segmented Echo Planar Imaging
Sequence was evaluated for T2 relaxometry at 1.5T and 3T (GE medical systems).
The parameters of the stepped TE segmented Echo Planar Imaging Sequence were kept
identical at both 1.5 and 3T: TE=15.6,27,39,51,63,75,87,99 ms; TR= 4000ms;
FOV=22*22;Slice thk/gap: 3/3; # Shots=14; Scan time=8 min. The MSE sequence
parameters were set close to the EPI sequence on both scanners (scan time: 18
mins). RESULTS: The EPI image quality at 1.5 T was comparable to MSE sequence; at
3T ghosting artifacts could be seen in EPI images. The log linear plot of signal
intensities of the segmented EPI sequence for irradiation in the range 0-20 Gy is
shown at 1.5 and 3T (fig 1 & 2). The T2 values agreed with that of corresponding
MSE sequences at both 1.5 and 3Tand the fit was much better using the segmented
EPI sequence than the MSE sequences. The dose calibration factor,a, was similar
for all the sequences (fig. 3- 3T a: MSE=0.93, EPI=0.99; fig.4- 1.5T a: MSE=0.79,
EPI=0.95) Conclusions: The EPI image quality at 1.5T was comparable to MSE. The
dose calibration factor evaluated with the EPI sequences was comparable at 1.5T
and 3T and close to the MSE sequence. Acquisition time of EPI is less than half
of MSE sequence with more flexibility in choice of TEs .The study establishes EPI
as a novel sequence for dose mapping.
PMID- 28518939
TI - SU-E-J-128: Liver Motion during CBCT-Guided SBRT.
AB - PURPOSE: Purpose of this study was to investigate the motion characteristics of
liver during SBRT, based on fiducial markers tracked with X-ray projections of
CBCT scans, taken immediately prior to each treatment. METHODS: Purpose of this
study was to investigate the motion characteristics of liver during SBRT, based
on fiducial markers tracked with X-ray projections of CBCT scans, taken
immediately prior to each treatment. RESULTS: The range of motion for twenty
patients were 3.00 +/- 2.04 mm, 5.08 +/- 3.12 mm and 17.93 +/- 5.11 mm in the
planning 4DCT, and 2.77 +/- 1.6 mm, 5.29 +/- 3.10 mm and 16.46 +/- 5.69 mm in the
treatment CBCT, for LR, AP, and CC directions, respectively. The range of
respiratory period was 3.94 +/- 0.65 and 4.18 +/- 0.75 seconds during 4DCT
simulation and CBCT scans, respectively. We found that breathing-induced AP and
CC motions are highly correlated. The absolute difference in motion magnitude
between the markers, had a positive correlation with absolute distance between
the markers (R2=0.69, linear-fit). The inter-fractional gating window varied
significantly for some patients, with the largest having 29.5-56.4% range between
fractions. CONCLUSIONS: This study analyzed the liver motion characteristics of
20 patients undergoing SBRT. A large variation in motion was observed, inter- and
intra-fractionally, and that as the distance between the markers increased, the
difference in the absolute range of motion also increased. This suggests that
marker(s) in closest proximity to the target be used. This project was supported
by Varian Medical Systems.
PMID- 28518940
TI - SU-E-J-139: Feasibility of Using EPID for Real-Time Target Localization during
Treatment.
AB - PURPOSE: This study aims to investigate the feasibility of using the images of
the treatment fields acquired by an electronic portal imaging device (EPID) for
real-time target localization. METHODS: Forty one patients treated with IMRT and
RapidArc were recruited in this study including 37 prostate patients and 4 lung
patients. These patients were grouped as: prostate IMRT with lymph node (n=14),
prostate IMRT without lymph node (n=17), prostate RapidArc (n=6), and lung IMRT
(n=4). For each patient, two to four fiducial markers were implanted inside the
tumor. The DRR, which projects the patient anatomy and the fiducial marker at the
EPID location, was reconstructed for each field. The MLC aperture of each control
point was overlay on its corresponding DRR to evaluate the fractional time when
the fiducial marker was seen on the EPID image. The probability of seeing at
least one, two, three, and four fiducial markers during the treatment was
recorded. RESULTS: For the prostate IMRT patients without lymph nodes included in
the target volume, the average probability of seeing at least one, two, three,
and four fiducial markers during the treatment was 50% (35%-59%), 39% (23%-51%),
24% (7%-38%), and 12% (4%-29%), respectively. For the prostate IMRT patients with
lymph nodes, the probability was 41% (24%-51%), 29% (12%-42%), 15% (3%-24%), and
7% (4%-15%), respectively. For prostate RapidArc treatments using two arcs, the
average probability of seeing at least one fiducial marker was 81% (58%-90%) for
the full arc and 74% (53%-94%) for the partial arc. For the lung IMRT treatment,
the average probability of seeing at least one fiducial marker was 34% (20%-52%).
CONCLUSIONS: The continuous image acquisition from the EPID during the treatment
provides sufficient target movement information for real-time target localization
and intrafractional target motion correction for advanced radiotherapy
treatments.
PMID- 28518941
TI - SU-E-J-171: Evaluation of Cervical Spine and Mandible Reproducibility of the CDR
Mayo Mold and Civco Type-S Head and Neck Immobilization Systems.
AB - PURPOSE: To evaluate the cervical spine (c-spine) and mandible reproducibility of
the CDR Mayo Mold and Civco Type-S head and neck immobilization system using
Mosaiq Setup Intelligence Curve Image Registration Methods: Patients were
immobilized with either the Mayo Mold or Civco Type-S head and neck
immobilization systems. Using curve image registration tools in Mosaiq, the c
spine and mandible were outlined. For each lateral image, two separate image
registrations were performed using an initial kV image as reference - 1) c-spine
only 2) mandible only. To evaluate the relative difference between the c-spine
and mandible position, the mandible image registration results were subtracted
from the c-spine image registration results. To evaluate whether the initial
difference between the planning CT and the first kV setup image is larger than
subsequent daily imaging variations, the difference in the image registration of
the DRR was compared to the variation in subsequent image registrations. The
degree of neck flexion was determined by observing the amount of mismatch between
the upper and lower cervical spine after the pitch correction. RESULTS: During
the first weeks of treatment, there was minimal difference in the image
registration results for both the c-spine and mandible individually, and in the
relative difference between them. For neck flexion, the Mayo Mold system
demonstrated 82.6% minimal difference and 3.8% significant difference between the
alignment of upper and lower c spine, vs. 84% and 5.2% for the S frame. For some
patients, there is a greater difference between the DRR and the initial kV image
registration than the variation in registrations for subsequent daily imaging.
CONCLUSIONS: Preliminary results indicate minimal difference in the c-spine and
mandible reproducibility between the two immobilization systems during the first
weeks of treatment. Further analysis of whether this minimal difference remains
consistent throughout the entire course and treatment and with greater number of
patients is needed.
PMID- 28518942
TI - SU-E-J-149: Is Rotational IMRT More Susceptible to Tumor Motion than Dynamic
IMRT?
AB - PURPOSE: To investigate whether rotational IMRT is more susceptible to organ
motion than IMRT that uses fixed fields. METHODS: RapidArc and sliding window
IMRT treatment plans were each created for five lung and five pancreas cases.
Dosimetric effects due to tumor motion were simulatedby incorporating sinusoidal
couch motion into plans using in-house Monte Carlo dose verification software.
Motion was emulated longitudinally (10 mm) for all cases with additional lateral
and vertical motion (5 mm) for pancreatic tumors. Dose distributions of original
and modified plans were compared using Gamma analysis and dose profiles. RESULTS:
Preliminary results show that for one lung case, a 95% Gamma pass rate can be
achieved using 6%-6-mm criterion for RapidArc versus 8%-8-mm for sliding window.
Findings are supported by expanding on a well-known model that demonstrates the
effects of intra-fraction motion on the delivery of dynamic intensity modulation.
CONCLUSIONS: Rotational IMRT deliveries are believed to be no more susceptible to
organ motion than sliding window IMRT, and results thus far support this
conclusion.
PMID- 28518944
TI - SU-E-J-159: Electromagnetic Tracking during 4DCT.
AB - PURPOSE: Real-time, electromagnetic tumor tacking during 4DCT is an unsolved
problem. The underlying problem is due to eddy current magnetic fields generated
within the conducting surfaces in response to the source's alternating magnetic
fields.To solve this problem, we developed a method to separate the source from
the background fields, which can be measured with simple search coil sensors,
such as those used by the Calypso (Seattle, WA) tracking system. METHOD: We
modeled the environment using ANSYS Maxwell electromagnetic simulation software.
The gantry was modeled as a 5 mm thick * 1.2 m diameter stainless-steel cylinder,
with variable length. The transponder solenoid was modeled as a 10 mm * 1 mm
conducting cylinder, with azimuth directed current, which was assumed to have a
frequency range of 300-500 kHz. The search coil configuration was assumed to be a
5 * 5 array of 5-7 cm square current loops with 6.7 cmseparation. An algorithm
based on free space calculations and measurements was developed to calculate the
solenoid position within the cylinder, in the presences of relatively large eddy
magnetic fields that were generated at the same frequency as the source. RESULTS:
Of the various methods and sensor configurations investigated, we found a method
that localized the transponder solenoid within 1 mm over all solenoid locations
and gantry lengths. We also found that gradient techniques did not significantly
increase localization accuracy as expected. Complex solutions were found but not
suitable for rapid clinical implementation. CONCLUSIONS: This method can be used
to localize a Calypso(r) Beacon transponder during 4DCT to accurately track tumor
positions. Furthermore, the method was based on inexpensive search coils with
comparable dimensions to preserve the source-sensor distance. The next task is to
create a system and investigate clinical implementation.
PMID- 28518943
TI - SU-E-J-180: A Characterization of the LAP Aquarius Phantom for External LAP Laser
Alignment and MR Geometric Distortion Verification for the use of SRS Patient
Simulation.
AB - PURPOSE: To explore additional application of the new Aquarius external laser
alignment verification Phantom by LAP (Aq-LAP Phantom) examining geometric
accuracy of magnetic resonance images (MRI) commonly used for planning
intracranial stereotactic radiation surgery (ICSRS) cases. METHODS: Newly
designed external patient alignment lasers were first aligned by the Aq-LAP
Phantom at a Siemens Magneton Vario 3T MR unit. The scans were then performed
with the T1 Axial 3D MPRAGE protocols with 0.9 mm temporal resolution, which may
be used for ICSRS. They also include FLAIR, T2 BLADE and Diffusion Axial TRACE
imaging acquisitions with 1 mm temporal resolution. The MRI will be fused to 1 mm
cut computerized tomography (CT) images acquired by a Siemens Somatom Sensation
Open(c). The geometric distortions (GD) were measured against the CT in all
axial, sagital, and coronal directions at different levels. RESULTS: MR images of
the Aquarius Phantom indicate a distinct similarity between the nonlinear GD
along the z-axis crosshair and typical magnetic field gradient nonlinearity.
There is linear correlation between MR divergence datasets of distorted
crosshairs (p-values from 0.57 to 0.00), and nonlinear correlation between MR
divergence datasets of the distorted crosshair with the CT divergence datasets of
the cross plane (p-values from 8.45*10-4 to 1.38*10-46). The margin of error
exceeded no more than 0.29 mm. GDs up to about 2 mm are observed at the distal
regions of the longitudinal axis in the SRS treatment planning MR images.
CONCLUSIONS: Using the Aquarius Phantom, one is able to detect GD in ICSRS
planning MRI acquisitions, and align the external LAP patient alignment lasers by
following the LAP QA. Based on the results, one may recommend using the Aquarius
Phantom to determine if margins should be included for SRS treatment planning.
The Aquarius Phantom, used for laser alignment and geometric distortion
detection, was provided by LAP of America.
PMID- 28518945
TI - SU-E-J-132: Quantitative Assessment of CT Number Variation Induced by Respiratory
Motion Artifacts in CT and Cone-Beam CT.
AB - PURPOSE: CT number variations due to image artifacts induced by respiratory
motion in CT and cone-beam CT (CBCT) imaging were investigated. A model was
developed to predict CT number variations observed in CT and CBCT images. METHOD
AND MATERIALS: Three target volumes of differing sizes were constructed of tissue
equivalent gel material and embedded into an artificial lung phantom. This mobile
phantom mimicked respiratory motion with eight different amplitudes of
respiratory motion in the range 0-20 mm at a frequency of 15 cycles/min. A model
was developed allowing for simulation of the observed CT number variation as a
function of the target volume, phantom motion frequency and amplitude and speed
of CT scanning. The simulation results were compared quantitatively with CT
profiles that were obtained from CT and CBCT imaging. RESULTS: The size and
distribution of CT numbers of well-defined homogenous targets varied with
respiratory motion. In CBCT, CT number variations depends mainly on the target
size and motion amplitude. Targets with a dimension smaller than the motion
amplitude show highest CT number densities at the edges of the elongated volume.
Conversely, targets larger than motion amplitude showed greatest CT number
densities in the middle of the target. In CT imaging, CT number variations were
more complicated and further depends on the speed of CT scanning where some
targets were elongated or shrunk with varying CT number gradients depending on
the above parameters. CONCLUSION: The sizes and CT number distributions varied
with motion for the homogenous targets. The CT number variations were modeled and
simulation provided comparable distributions to those observed in CT and CBCT
images based on target size, amplitude, frequency, and scanning speed. The
results here might provide useful tools to correct image artifacts and consider
CT number variation due to motion in treatment planning and dose delivery.
PMID- 28518946
TI - SU-E-J-164: Verification of Commercial Respiratory Tracking System Using
Scintillation Screen.
AB - PURPOSE: The accuracy of the tracking system is critical for the result of four
dimensional radiation therapy. The objective of this study is to propose the
method of verifying the accuracy of respiratory tracking system. METHODS: The
scintillation screen and the light marker between the transparent acrylic plates
were designed to move according to the prerecorded respiratory organ motion of
volunteers. A vertical circle photon beam with 3 cm diameters from the cyberknife
unit was planned to track the motion of the scintillation screen with the plates.
In dark room, the CCD camera outside of the phantom captured the scintillation
from the screen and the light marker in 30 frames per second when the photon beam
was incident. The pictures were captured by the CCD camera were analyzed frame by
frame, and the discrepancy between the scintillating circle on the scintillation
screen and the light marker depending on the time was measured. The discrepancy
of the motions of the delivered photon beam and the light marker was analyzed.
RESULTS: In the preliminary study, the maximum discrepancy was measured less than
1.5 mm in normal breathing pattern as the manufacturer specified it. CONCLUSIONS:
As the speed of the motion was increased, the discrepancy between the position of
the beam and internal marker increased. However, the error was clinically
acceptable. The further study will be performed for the irregular respiratory
motion patterns. This research was supported by Basic Science Research Program
through the National Research Foundation of Korea (NRF) funded by the Ministry of
Education, Science and Technology (20110004848).
PMID- 28518947
TI - SU-E-J-143: Characteristics of Tumor-Motion Surrogate Signals Analyzed Using
Empirical Mode Decomposition and Hilbert-Huang Transformation.
AB - PURPOSE: We introduce a novel technique for analyzing tumor-motion surrogate
signals using Empirical Mode Decomposition (EMD) and Hilbert-Huang Transformation
(HHT). METHODS: The tumor-motion surrogate signals were acquired (with
RPM/Varian), from 20 lung-cancer patients in free-breathing method and its data
were decomposed into Intrinsic Mode Functions (IMFs) using EMD. HHT was then
applied to each IMF to obtain instantaneous frequency as a function of time. The
Result of the frequency information was compared to Fast Fourier Transformation
(FFT) and manual calculation of frequency. Correlation of each IMF with the
surrogate signal was used to determine the adequate IMF as a faithful tumor
motion surrogate. RESULTS: The surrogate RPM signals were decomposed to 10 +/- 1
IMFs on average. The decomposed IMFs showed three categories of frequencies: (1)
high frequencies (1 - 10 Hz) such as a noise-like signal, (2) medium frequencies
(0.1 - 0.3 Hz), which is potentially a true breathing signal, and (3) low
frequencies (0.003 - 0.09 Hz), which behave a baseline drift. The marginal
frequency, which is a measure of total amplitude contribution from each
frequency, showed an average difference of -0.03 +/- 0.07 from the FFT and -0.02
+/- 0.05 with the manual calculations. Each surrogate signal showed a high
correlation with one IMF (0.747 on average) and, a low correlation with the rest
of the IMFs (0.139 on average). The IMF with a high correlation alone represented
the surrogate signal well in terms of breathing frequency and amplitude.
CONCLUSIONS: The EMD and HHT were used to analyze the cyclic components of
nonlinear and non-stationary surrogate signals in the time domain. Since the EMD
decomposes the signal into physically-meaningful modes, it was possible to
determine IMFs that represent the tumor motion faithfully after removing noise
like signals. Further investigation on physical meanings of the IMFs is the next
step of the study.
PMID- 28518948
TI - SU-E-J-175: A Patient-Specific 4D Digital Phantom for Dynamic Dose Estimation of
External Ionizing Radiation.
AB - PURPOSE: To develop a realistic yet flexible 4D digital phantom based on patient
anatomy for dynamic estimation of organ doses due to external ionizing radiation.
METHODS: In this work, we propose to build a 4D digital phantom based on patient
CT anatomy and time-tagged CT information. A regional 4D-CT is first acquired on
the patient around lesion with a RPM system. By binning CT information at various
phases of respiratory motion, we can create a regional 4D phantom. By applying
non-uniform rational B-spline (NURBS) surface technology, we can easily
accommodate the size-specific and gender-specific differences in the organ shapes
and body contours, often observed during a long course of radiotherapy
treatments. Based on the ICRP reference phantoms, we can extend the patient
specific 4D regional phantom into a 4D whole-body phantom unique to each patient.
The resultant 4D phantom will serve as the digital representative of the patient
himself or herself in the virtual environment and is ready for Monte Carlo
particle transport. RESULTS: Considering the newborn skin thickness (0.663 mm),
0.5 mm is defined as the maximum voxel resolution available in our 4D digital
phantom. The resultant 4D digital phantom is essentially a high-resolution voxel
phantom (with voxel dimensions down to 0.5 mm * 0.5 mm * 0.5 mm) capable of non
uniform scaling of organs and body contours based on NURBS surface technology.
CONCLUSIONS: It is feasible to build a 4D patient-specific digital phantom
suitable for Monte Carlo radiation transport simulation. With a digital phantom
for each patient, an accurate estimation of the organ doses in 4D will be made
possible, which will contribute to a better tumor control because of the detailed
knowledge of dose distributions in patient anatomy not only spatially but also
temporally. The proposed 4D phantom will also allow for deformable dose
registration for adaptive radiotherapy.
PMID- 28518949
TI - SU-E-J-168: 4D-PET for Target Volume Delineation in Respiratory-Gated Radiation
Therapy.
AB - PURPOSE: To find an optimized workflow for the use of respiratory-gated PET (4D
PET) in target volume delineation of tumors subject to respiratory-gated
radiation therapy. METHODS: 15 patients with lung (11) and pancreas (4) tumors
who had FDG-PET-CT for target delineation prior to EBRT were studied. Patients
were selected among the group that showed respiratory-induced tumor motion >5mm.
4D-PET was performed by means of a Philips Gemini BigBore scanner, using the
Varian RPM gating system. An identical system was available at the linac for
treatment. The breathing cycle was equally divided in 4 phases, according to a
previous study. Since planning was made on a single CT-phase, no ITV was
explicitly built from the set of phases. The BTV was identified with SUV=2.2
threshold and the PTV was obtained expanding the BTV by 8mm(S-I), 5mm(A-P) and
3mm(L-R) to account for residual motion and setup errors. The most advantageous
CT-phase for treatment planning was then identified by simulating plans on each
phase and analyzing the resulting DVHs of OARs (lung, trachea, oesophagus, spinal
cord, left ventricle). RESULTS: The observed maximum range of motion was 5.5mm(L
R), 12.3mm(A-P) and 19.2mm(S-I). The standard deviation of the BTV volume in the
4 phases ranged from 6% to 13.7%. V20 (lung) ranged 7.1%-15.2% in inspiration and
7.8%-18.6% in expiration. The mean dose to the oesophagus ranged 0.1-2.2Gy in
inspiration and 1.4-2.0Gy in expiration. In general, the dose to OARs was smaller
when planning on a single phase than on the overall, respiratory-uncontrolled
volume (p-value<0.05). CONCLUSIONS: The BTV volume was almost constant between
phases, confirming that the motion might be described by 4 phases. There was no
obvious choice of the optimal phase for treatment planning, suggesting patient-by
patient studies. However, planning and delivery on one phase consistently allowed
dose sparing to be obtained compared to non-gated techniques.
PMID- 28519009
TI - SU-E-J-189: The Kullback-Leiber Divergence for Quantifying Changes in
Radiotherapy Treatment Response.
AB - PURPOSE: Repeated imaging is an extremely powerful tool in current radiotherapy
practice since it allows advanced tumor detection and personalized treatment
assessment by quantify tumor response. Change detection algorithms have been
developed for remote sensing images to mathematically quantify relevant
modifications occurring between datasets of the same subject acquired at
different times. We propose usage of change detectors in radiotherapy for an
automated quantification of clinical changes occurring in repeated imaging.
METHODS: We explore usage of the Kullback-Leiber divergence as indicator of tumor
change and quantification of treatment response. The Kullbach-Leiber divergence
uses the likelihood theory to measures the distance between two statistical
distributions and thus does not assume consistency in imaging. By it's general
nature, it can accommodate the presence of noise and variations in imaging
acquisition parameters that usually hinder automated identification of clinically
relevant features. RESULTS: In a comparison of simple difference maps and the
Kullbach-Leiber divergence operator, the difference maps were affected by noise
and did not consistently detect changes of low intensity. In contrast, the
proposed operator discerned noise by considering regional statistics around each
voxel, and marked both regions with low and high contrast changes. CONCLUSIONS:
Statistical comparison through Kullback-Leiber divergence provides a reliable
means to automatically quantify changes in repeated radiotherapy imaging.
PMID- 28519011
TI - SU-E-J-201: What is the Importance of Dose Recalculation for Adaptive
Radiotherapy Dose Assessment?
AB - PURPOSE: To quantify the effect of using the planned dose distributions in lieu
of performing dose recalculations on daily in-room images for adaptive
radiotherapy (ART) dose assessment of head and neck cancer patients. METHODS: 16
patients with cancers of the head and neck were treated using the TomoTherapy Hi
Art II (Accuray Inc., Sunnyvale, CA). Images of all patients were acquired prior
to each treatment using the megavoltage CT (MVCT) capability of the TomoTherapy
unit. Overall, images from 528 fractions were evaluated. For every image set, the
delivered dose was estimated by both recalculating the dose distribution using
the acquired MVCT and also by simply overlaying the planned distribution on the
new images. ART dose assessment was performed using deformable image registration
(DIR) to deform contours from the treatment plan to the images acquired during
each fraction and to accumulate the estimated dose delivered during each fraction
back to the reference treatment plan. The same DIR maps were applied to both dose
estimation methods. Dosimetric endpoints were then compared between the DVHs
computed using the recalculated or planned dose distributions. RESULTS: The mean
PTV D95% and D05% endpoints were 0.6+/-0.5% and 1.4+/-0.8% lower using the
planned dose distributions compared to the recalculated distributions,
respectively, across all patients. The mean parotid D50% was 2.4+/-1.5% greater
using the planned distributions compared to the recalculated distributions. The
parotid D50% from the planned distributions was also highly correlated with the
parotid D50% from the recalculated distributions for each patient (mean r2=0.97+/
0.09). CONCLUSIONS: For this treatment modality and site, dosimetric differences
observed between overlaying the planned dose distributions and recalculating
distributions on daily images were typically well within +/-5%. This indicates
that the dose distribution itself is robust against anatomic variations. This
study was funded, in part, by a grant from Accuray Inc.
PMID- 28519010
TI - SU-E-T-16: Statistical Variability and Confidence Intervals for Planar Dose QA
Pass Rates.
AB - PURPOSE: The most common metric for comparing measured to calculated dose planes
is a pass rate generated using percent difference, distance-to-agreement (DTA),
or some combination of the two (e.g. gamma evaluation). The grid of analyzed
points often corresponds to a dosimeter array with low areal-density of point
detectors. This work examines the statistical uncertainty of planar dose
comparison pass rates and proposes methods for establishing confidence intervals
for pass rates obtained with low detector-density arrays. METHODS: Absolute dose
planes were acquired via EPID for twenty intensity-modulated fields of varying
complexity. Matching calculated dose planes were created via treatment planning
system. Pass rates for each dose plane pair (centered to CAX) were calculated
with various %/DTA composite analysis techniques. Software was designed to
selectively sample the high-density EPID matrix to simulate many low-density
measured grids, each representing a different alignment with respect to CAX.
Simulations were repeated (100 positional iterations per field) using grids of
varying detector-densities and both random and orthogonal point-detector
orientation. For each simulation, pass rates were calculated with various
composite analysis techniques. RESULTS: Repositioning simulated low-density grids
leads to a distribution of possible pass rates for each measured/calculated dose
plane pair, independent of whether the detector grid is random or uniform.
Distributions can be predicted using a binomial distribution by which a
confidence interval (function of sampling density and observed pass rate) is
approximated for each pass rate. For example, 95% confidence intervals for IMRT
pass rates (2%,2mm) average +/-5.3% and +/-3.8% with 1-detector/cm2 and 2
detector/cm2 grids, respectively. CONCLUSIONS: Pass rates for low-density array
measurements are not absolute and should be reported with both a full description
of calculation method and confidence intervals quantifying their uncertainty.
Results extend to 3D detector arrays. The concept of fixed 'action levels' for
pass rates must be reexamined for low-density array measurements.
PMID- 28519012
TI - SU-E-T-26: Evaluation of New Pre-Treatment In-Air Patient Specific QA Software
for TomoTherapy Treatments.
AB - PURPOSE: Math Resolutions, LLC, has extended their Dosimetry Check quality
assurance software to include TomoTherapy treatments. Data collected from
TomoTherapy's MVCT detectors is processed and compared to the planned treatment
dose allowing for pre-treatment QA without the use of phantoms and other
detectors. This study presents an overview of our experience at the University of
Virginia developing, implementing, and verifying this novel QA strategy. METHODS:
Low modulation and high modulation cheese phantom plans as well as patient plans
(prostate, GYN, and vertebra) were used to test the Dosimetry Check in-air
software. For all evaluations the treatment table was removed from the XML file
of each plan using software provided by Accuray and the resulting in-air
calibration plan was delivered. The exit detector sinogram was extracted from the
machine and imported into Dosimetry Check along with the TomoTherapy calculated
planned dose. The fluence maps were reconstructed and used to recalculate the
dose. RESULTS: The percent difference between the planned dose and the dose
calculated from the exit detectors by Dosimetry Check ranged between 0.62% for a
simple low modulation cheese phantom plan with a cylindrical target to 7.3% for a
high modulation 2.5cm prostate plan. The gamma indices reported range from 94.7%
to 97.8% <1 over the overall calculation area for the plans tested using a gamma
of 3% and 3mm. For the area receiving over 80% of the prescribed dose, the gamma
ranged from 80.7% to 92.9% <1. CONCLUSIONS: The results of our investigation of
Math Resolutions' new product in development, Dosimetry Check's pre-treatment in
air QA software, demonstrate that it has the potential be a very useful and
practical tool for TomoTherapy QA. Further testing is being performed in which
various errors are intentionally introduced in the delivered dose to test the
limits of Dosimetry Check's sensitivity. Research Grant from Math Resolutions LLC
01/12/2012-01/11/2013 Math Resolutionsa?TM Dosimetry Check software was given to
UVa to assist with evaluating the precision of the product in reconstructing dose
from the TomoTherapy exit detector data.
PMID- 28519013
TI - SU-E-J-212: Real-Time Treatment Failure Detection for Moving Tumor with Image
Guidance.
AB - PURPOSE: Respiratory motion can cause misalignment of the radiation beam and will
greatly degrade the effectiveness of cancer radiation treatment. Failure of
radiation treatment can be detected by real-time image. The efficiency of both
internal tracking and external tracking has been assessed in this. METHODS: Both
3D internal fiducial marker motion and 1D external abdominal surface motion data
of 11 patients were collected simultaneously. Linear and quadratic functions have
been applied to correlate the internal and external motion signal. To detect
tracking failure of external imaging, three approaches have been proposed: (i)
correlation only: which will compare directly between the tracked and the based
curve. (2) fixed baseline shift: which interferes the treatment by adjusting the
baseline of tracked signal to compensate target motion for each treatment
fraction. (3) dynamic baseline shift: dynamically interfere with treatment for
each breathing cycle. (4) dynamic baseline with base curve update, is the third
approach with base curve for each fraction. RESULTS: Generally, the quadratic
function produced better correlation results than the linear correlation. With
more historical data available, the quadratic prediction gives better correlation
outcomes. The tracking frequency of 30, 10, 5, 2, 1, and 0.2Hz has been
evaluated. Although high imaging frequency usually results in better correlation,
imaging rate of 1 Hz will results acceptable results. For the failure detection,
the average Euclidean misalignment is 3.46, 2.42, 2.21, 1.80 for the above four
approach. With treatment interference, the beam-on-time percentages are 54.03,
58.26, 63.94, and 60.48 respectively. CONCLUSION: High imaging frequency is not
required. approaches with baseline shift and base curve update will improve the
treatment efficiency and treatment accuracy. Guidance using hybrid imaging with
high-frequency of external imaging and low internal imaging is needed to
compensate tumor respiratory motion.
PMID- 28519014
TI - SU-E-J-182: Patient Specific Assessment of External Radiation Exposure to
Bystanders Interacting with Patients Following 131I Therapy.
AB - PURPOSE: Conventional calculation methods of patient release criteria for
compliance with NRC regulations are based on the assumption that both patient and
bystander are each a single point in space. This study was intended to assess the
patient-specific external radiation exposure to a bystander interacting with the
patient following radionuclide therapy with 131I. METHODS: 131I-sodium iodide
treatment for hyperthyroidism and thyroid cancer and 131I-tositumomab treatment
of non-Hodgkin's lymphoma were considered. 131I distribution provided by the
patient SPECT image was rendered on the SPECT-fused CT images. The CT images were
then imported to a Monte Carlo based simulation code, MCNPX 2.7, as a source
phantom. For a target phantom, we employed the adult male hybrid phantom
developed at the University of Florida and National Cancer Institute. A single
orientation - patient and a bystander facing one another at 1.0 m - was
considered. S factors (dose per unit cumulative activity (A)) for each organ in a
bystander was obtained from the MC calculations and effective dose (EDE) per A
was calculated based on tissue-weighted individual organ doses. The results were
compared with the calculations using UF/NCI adult hybrid source/target phantoms
and the revised adult ORNL stylized source/target phantoms. RESULTS: EDE per A of
the stylized phantom was 1.5% higher than that of the hybrid phantom for uniform
source localization in the thyroid. However, EDE per A of the hybrid phantom was
20% less than that of stylized phantoms for a torso source. The difference is
attributed to the realistic shape of the frontal body comparing to the simple
ellipsoidal trunk of the stylized phantom. CONCLUSIONS: Based on the realistic
hybrid phantoms and accurate MC radiation transport calculation tools, patient
specific dosimetry for a bystander is feasible. S factors will be calculated
using the patient CT image with 131I bio-distributions and hybrid phantoms.
PMID- 28519015
TI - SU-E-T-09: Empirical Evidence for Decreased Cell Survival in Flattening Filter
Free Beams.
AB - PURPOSE: To present empirical evidence for a decrease in cell survival with the
introduction of markedly increased average dose rates in flattening filter free
beams. METHODS: Data of (Bewes et al., 2008) are used to calculate a modification
factor for cell survival curves, using the linear quadratic model, that is
inversely proportional to the reciprocal of the average dose rate. RESULTS: The
survival curve becomes steeper as the average dose rate increases above a ~600
cGy/min threshold. For average dose rates below this threshold, no significant
effect or even an increase in cell survival was observed (as explained by the Lea
Catcheside dose protraction factor). For a maximum assumed dose modification
factor of 1.2 a decrease in cell survival of 3.5% for a dose of 2Gy and 36% for a
dose of 8 Gy is predicted for a MM576 cell line. For a maximum assumed dose
modification factor of 1.4 a decrease in cell survival of 60% for a dose of 2Gy
and 1 order of magnitude for a dose of 8 Gy is predicted for a NCI-H460 cell
line. For a dose modification factor of 2.65 with a dose rate of 24 Gy/min, a
decrease in cell survival of 1 order of magnitude at 2Gy and 5 orders of
magnitude at 8 Gy is predicted for a NCI-H460 cell line if it is assumed that the
inverse proportionality is true. CONCLUSION: Although no effects on cell survival
was seen previously with clinically achievable dose rates (except for enhanced
cell survival through repair for increased treatment times), it might become more
evident with the increase of the average dose rate in flattening filter free
beams. This will necessitate revision of fractionation schemes and maximum
tolerable doses for organs at risk for stereotactic body radiation therapy.
PMID- 28519016
TI - SU-E-J-193: Gamma Knife Perfexion End-To-End Testing with a Commercial
Stereotactic Phantom.
AB - PURPOSE: To investigate the use of the Lucy (r) Stereotactic Phantom (Standard
Imaging, Inc.) for Gamma Knife Perfexion radiosurgery quality assurance of the
imaging, treatment planning, and dose delivery processes. End-to-end testing of
the Perfexion and Gamma Plan version 10.1 has not been previously examined in
literature. METHODS: The phantom was imaged using both the CT and T1- and T2
weighted MR sequences used for treatment planning. For imaging, the isocentric
volume insert and fiducial markers were positioned within the phantom. Scans were
transferred to the Gamma Plan treatment planning system and were evaluated for
geometric and fusion accuracy. A plan was created to deliver 12Gy to the 50%
isodose line to the 5.25cm3 volume. During dose delivery, Gafchromic EBT2 film
was positioned in the film insert to replicate the position of the target volume.
Dose results were analyzed using RIT software (Radiologic Imaging Technology,
Inc.). RESULTS: Image fusion integrity was inspected by overlaying the MR and CT
markers (5 fiducial markers spaced 5mm apart) and visually examining the
resulting volume insert overlap between the three scans. Geometric accuracy was
evaluated by contouring three volumes using Gamma Plan contouring tools.
Agreement within 1.1%, 6.7% and 12.2% of the actual volumes was seen with the T1
weighted, T2-weighted, and CT images, respectively. The volume-based acquisition
and 1mm slice thickness of the T1-weighted sequence resulted in the most accurate
measurement. Geometric measurements along two dimensions showed acceptable
accuracy for all imaging modalities within 1.6%. Dosimetry results agreed well
with the planned dose. The EBT2 film was calibrated for absolute dose
measurements using a dose calibration curve for 0.1-30 Gy and the calibration
curve was verified to have <3% error above 1Gy. CONCLUSIONS: The Lucy phantom
allows for comprehensive quality assurance testing of the Gamma Knife Perfexion
radiosurgery process.
PMID- 28519017
TI - SU-E-T-20: Removal of Electron Contamination in Longitudinal Field MRI-Linac
Systems: A Monte Carlo Study.
AB - PURPOSE: The prototype inline MRI-linac system has some advantages over
perpendicular models including avoiding the electron return effect. One of the
disadvantages of the inline approach is the increased skin dose, estimated to be
400-1000% of the dmax dose. The purpose of this work was to design a feasible
method to reduce this skin dose to acceptable levels. METHODS: Magnetic modeling
of proposed MRI-linac designs have been simulated with the inclusion of an
optimized permanent magnet system to purge/deflect the electron contamination.
The region of air above the phantom was also replaced with a helium bag (region
of helium gas) and a beam scrapper below the deflector was added to collect
deflected off-axis contamination. Monte Carlo simulations were then performed
including the accurate 3D magnetic field maps. Surface dosimetry was recorded to
verify the changes to the skin doses. RESULTS: Magnetic modelling showed that an
optimized NdFeB permanent magnet system located outside the MRI coils (below the
MLC's) can provide a strong enough region to purge/deflect a significant portion
of the electron contamination from the x-ray beam. The impact on the MRI
uniformity is around 100 ppm and hence is correctable via active/passive shimming
of the MRI. The helium region also significantly limits the production of
contamination traveling towards the phantom surface. Entry doses near CAX are
predicted to be similar to the 0 T case. CONCLUSIONS: Magnetic and Monte Carlo
modeling were performed to estimate the effect that a permanent magnet purging
system, beam scrapper, and helium bag would have on lowering the skin doses in an
inline MRI-Linac system. MRI non-uniformities introduced by the deflector could
be corrected, contamination is mostly purged or blocked, and the helium bag
minimizes air-generated contamination. As a result skin doses are comparable to
having zero magnetic field.
PMID- 28519018
TI - SU-E-J-205: Modeling Fiducial Marker Movement in Prostate.
AB - PURPOSE: To understand fiducial marker movement in prostate and to improve
prostate patient positioning with fiducial markers. METHODS: Patient planning CT
and positioning CBCT were retrospectively analyzed. CBCT images were
automatically registered to the corresponding CT ones based on their bony
structures in Eclipse. The coordinates of the markers in the CT and CBCT were
recorded. The status of bladder and rectum fillings, and gas in rectum were
indexed into four levels and recorded. An algorithm was developed to optimally
register the (three) fiducial markers in CBCT with those in the CT so that only
the information on prostate deformation and marker migration remained. A
mathematical model was built to estimate the marker migration and the relative
contribution to the deformation from the status change of bladder and rectum.
RESULTS: The registration error from our optimal registration algorithm indicates
the minimal patient setup error by using fiducial markers. The results from our
analyzed 3 patients were average(standard deviation) = 1.10(0.40), 1.27(0.67) and
0.62(0.38) mm, but there were some fractions when the registration errors were
over 2 mm. From our mathematical model, it was found that the marker migration
could be as large as 2.9 mm. If 2 mm tolerance is required in such as SBRT, then
soft tissue based registration may be more appreciated when the optimal
registration error is greater than 2 mm or from the date when the migration is
greater than 2 mm because the migrated marker may not change the location
thereafter. In addition, for one investigated patient, the relative contribution
to the deformation from the bladder, rectum filling and gas in the rectum is
0.43:0.31:0.26. More patient data are in analysis, and other interesting results
will be reported. CONCLUSIONS: Fiducial marker migration can be over 2 mm. The
migration will Result in a conclusion that small registration error does not mean
good patient positioning.
PMID- 28519019
TI - SU-E-T-02: Radiobiological Comparison of Two Treatment Schemas in IMRT Prostate
Radiotherapy.
AB - PURPOSE: Different fractionation schemas are used for the treatment of prostate
with IMRT. Due to the low alpha/beta of prostate hypofractionated schemas are
achieving more importance. The purpose of this study is to compare two IMRT
techniques from a radiobiological point of view in the treatment of high risk
prostate cancer, the sequential IMRT technique (SIMRT) and a simultaneous
integrated boost IMRT treatment (SIBIMRT). METHODS: 20 patients were selected and
planned using both treatment strategies to give an EQD2 of 82 Gy to prostate, 70
Gy to vesicles and 46 Gy to lymph nodes, using the linear quadratic model LQ
supposing an alpha/beta prostate=1.5 Gy. Dose volume histograms of prostate,
rectum and bladder were calculated. Tumour Control Probabilities (TCP) and Normal
Tissue Complication Probabilities (NTCP) were also calculated. As the prostate
alpha/beta is not known exactly the TCP has been calculated for different
a/bprostate values ranging from 1.5 to 10 Gy. NTCPs of bladder and rectum were
calculated also for alpha/beta oar values ranging between 1 to 15 Gy. RESULTS:
Both treatment strategies were found to be equivalent in terms of prostate ptv
TCP and EQD2 for low alpha/beta prostate=1.5 Gy. In the case of high alpha/beta
prostate values, 3 Gy and 10 Gy, EQD2 and TCP for prostate ptv are lower for the
SIBIMRT technique. For rectum and bladder, if a/boar ranges between 2 and 15 Gy
EQD2 values are higher for the SIMRT treatment schema. NTCP for bladder and
rectum is higher for the SIMRT technique when alpha/beta OAR >= 2 -3 Gy.
CONCLUSIONS: In this study a comparison between two treatments strategies have
been done. Our results show that a hypofractionated technique for high risk
prostate cancer reduces, or equals, EQD2 and NTCP for bladder and rectum while
maintaining the TCP of prostate for the typical alpha/beta values in use.
PMID- 28519020
TI - SU-E-J-186: CT Textures Can be Predictive for Tumor Shrinkage.
AB - PURPOSE: To determine if NSCLC GTV CT textures can be predictive for tumor
shrinkage after proton therapy with concurrent chemotherapy. METHODS: Simulation
and weekly 4DCTs were obtained from 25 patients with locally advanced NSCLC
treated by proton therapy at a 74 Gy dose level with concurrent chemotherapy. In
house deformable image registration software based on the demons algorithm
propagated the physician-generated planning GTV onto each weekly image set. GTV
soft tissue volumes were then extracted from CT images by in-house software which
pruned out voxels below a cutoff HU threshold. Patients whose normalized end
treatment pruned GTV was less than the group median were classified as 'strong
responders.'The remaining patients were classified as 'weak responders.' For each
pruned GTV, the MaZda texture analysis software generated quantitative 3D texture
features based on the image histogram, absolute gradient, co-occurrence matrix,
and run-length matrix. Using the Fisher coefficient, a subset of these texture
features that were relevant to distinguishing the two response groups was
obtained. In-house software and MaZda were then used to perform neural network
data classification with leave-one-out cross-validation based on this texture
feature subset. The true positive rate (TPR), false positive rate (FPR),
classification accuracy, and one-sided p-values were recorded. RESULTS: Six
classification models were tested. Each model had a unique combination of feature
extraction and analysis parameters. Taking 'strong responders' to be the
'positive' class, the average TPR was 0.66 (0.60 - 0.75), the average FPR was
0.36 (0.31 - 0.40), the average classification accuracy was 64.8% (60.0% -
68.0%), and the average one-sided p-value was 0.118 (0.055 - 0.215). CONCLUSIONS:
There is some evidence showing that NSCLC GTV CT textures can be predictive for
tumor shrinkage after proton therapy. Further work should be done to include more
patients, texture metrics, and data analysis techniques. The presenting author
receives funding support from a Hertz Foundation Applied Science Fellowship.
PMID- 28519021
TI - SU-E-T-13: Comparison of Dose Rates with and without Gold Backing of USC #9
Radioactive Eye Plaque Using MCNP5.
AB - PURPOSE: To show the effect of gold backing on dose rates for the USC #9
radioactive eye plaque. METHODS: An I125 source (IsoAid model IAI-125A) and gold
backing was modeled using MCNP5 Monte Carlo code. A single iodine seed was
simulated with and without gold backing. Dose rates were calculated in two
orthogonal planes. Dose calculation points were structured in two orthogonal
planes that bisect the center of the source. A 2*2 cm matrix of spherical points
of radius 0.2 mm was created in a water phantom of 10 cm radius. 0.2 billion
particle histories were tracked. Dose differences with and without the gold
backing were analyzed using Matlab. RESULTS: The gold backing produced a 3%
increase in the dose rate near the source surface (<1mm) relative to that without
the backing. This was presumably caused by fluorescent photons from the gold. At
distances between 1 and 2 cm, the gold backing reduced the dose rate by up to
12%, which we attribute to a lack of scatter resulting from the attenuation from
the gold. Dose differences were most pronounced in the radial direction near the
source center but off axis. The dose decreased by 25%, 65% and 81% at 1, 2, and 3
mm off axis at a distance of 1 mm from the source surface. These effects were
less pronounced in the perpendicular dimension near the source tip, where maximum
dose decreases of 2% were noted. CONCLUSIONS: I 125 sources embedded directly
into gold troughs display dose differences of 2 - 90%, relative to doses without
the gold backing. This is relevant for certain types of plaques used in treatment
of ocular melanoma. Large dose reductions can be observed and may have
implications for scleral dose reduction.
PMID- 28519022
TI - SU-E-J-197: A Novel Optical Interstitial Fiber Spectroscopic System for Real-Time
Tissue Micro-Vascular Hemodynamics Monitoring.
AB - PURPOSE: To demonstrate a novel interstitial optical fiber spectroscopic system,
based on diffuse optical spectroscopies with spectral fitting, for the
simultaneous monitoring of tumor blood volume and oxygen tension. The technique
provides real-time, minimally-invasive and quantification of tissue micro
vascular hemodynamics. METHODS: An optical fiber prototype probe characterizesthe
optical transport in tissue between two large Numerical Aperture (NA) fibers of
200MUm core diameter (BFH37-200, ThorLabs) spaced 3-mm apart. Two 21-Ga medical
needles are used to protect fiber ends and to facilitate tissue penetration with
minimum local blunt trauma in nude mice with xenografts. A 20W white light source
(HL-2000-HP, Ocean Optics) is coupled to one fiber with SMA adapter. The other
fiber is used to collect light, which is coupled into the spectrometer (QE65000
with Spectrasuite Operating software and OmniDriver, Ocean Optics). The
wavelength response of the probe depends on the wavelength dependence of the
light source, and of the light signal collection that includes considerable
scatter, modeled with Monte-Carlo techniques (S. Jacques 2010 J. of Innov. Opt.
Health Sci. 2 123-9). Measured spectra of tissue are normalized by a measured
spectrum of a white standard, yielding the transmission spectrum. A head-and-neck
xenograft on the flank of a live mouse is used for development. RESULTS: The
optical fiber probe delivers and collects light at an arbitrary depth in the
tumor. By spectral fitting of the measured transmission spectrum, an analysis of
blood volume and oxygen tension is obtained from the fitting parameters in real
time. CONCLUSIONS: A newly developed optical fiber spectroscopic system with an
optical fiber probe takes spectroscopic techniques to a much deeper level in a
tumor, which has potential applications for real-time monitoring hypoxic cell
population dynamics for an eventual adaptive therapy metric of particular use in
hypofractionated radiotherapy.
PMID- 28519023
TI - SU-E-T-23: TomoTherapy Patient QA Using Exit Detector Measurement of Pre
Treatment In-Air Delivery.
AB - PURPOSE: Currently, the recommended TomoTherapy patient specific QA involves
setting up a DQA procedure and delivering it to a phantom with an ion chamber and
film measurement. The process is time-consuming and the DQA result is susceptible
to errors in phantom setup. Our study explores the feasibility of using
TomoTherapy's intrinsic exit detectors to perform patient specific QA by
measuring the fluence received by the detectors during pre-treatment in-air
delivery for our STAT-RAD workflow. METHODS: A TomoTherapy patient plan is
converted into a calibration procedure in which the couch remains out of the
gantry. The signal measured by the exit detector is exported through manufactory
provided software. In-house developed software is used to reconstruct exit
detector signal from the dicom-exported delivery plan. The software relies on
individual leaf profiles as well as tongue-and-groove profiles of each adjacent
leaf-pair extracted from an in-house developed calibration procedure. The
difference between the reconstructed and measured detector signal can be analyzed
by a simple algorithm which has been developed to estimate the dose difference of
any given point inside a patient or phantom. Several patient plans have been
tested with this in-air delivery QA method. In some of the tested plans, errors
have been introduced to assure the estimated point dose error agrees with the ion
chamber measurement in a phantom. RESULTS: The in-house exit detector
reconstruction software has been validated to be able to reconstruct the exit
detector signal with errors <1%. The software estimated point dose agrees within
3% to the ion chamber measurement. CONCLUSIONS: Our study shows that it is
feasible and efficient to perform patient specific QA using the exit detector
signal recorded during the in-air pretreatment delivery. This approach is easy to
perform and it is faster than conventional QA approach.
PMID- 28519024
TI - SU-E-J-209: A Simple Method to Minimize Uncertainty in ITV Delineation: Phantom
Verification.
AB - PURPOSE: Irregular breathing causes variation in delineation of internal target
volume (ITV), which is typically generated in the maximum intensity projection
(MIP) images [1]. Previous studies have shown that MIP-based ITV can
underestimate true tumor range [2]. This study examines a simple method to reduce
such errors by combining the GTV of 3D-CT with the ITV of MIP. METHODS: The
Computerized Imaging Reference Systems (CIRS) Dynamic Thorax Phantom Model 008A
(CIRS, Norfolk, VA) with CIRS motion control software was used to model 4
irregular patient respiratory profiles and one regular respiratory profile (sine
wave). A 3 cm tumor insert was used as target. For each breathing profile, a 3D
CT and 3 repeated 4D-CT scans with random intervals within the breathing profile
were performed on a 4-slice clinical scanner (Lightspeed, GE, WI). The RPM system
(Varian, Palo Alto, CA) was used to track the respiratory profiles. GTV was
contoured on 3D-CT, and ITV was contoured on each MIP (ITVMIP) using a consistent
lung window by the same person. The new method of creating ITV was to combine the
GTV and ITVMIP, namely ITVCOMB. To evaluate which ITV is more accurate, ITVCOMB
and ITVMIP were compared to a 'ground truth' ITV (ITVGT) which was generated by
combining the three ITVMIPs. RESULTS: For the regular profile, both ITVMIP (27.25
cm3 ) and ITVCOMB (28.12 cm3 ) were comparable to ITVGT (27.25 cm3 ). For
irregular profiles, the mean absolute difference between ITVCOMB and ITVGT
(6.3%+/-4.9) was significantly (p-value=0.0078) smaller than that between ITVMIP
and ITVGT (18.1%+/-12.3). CONCLUSIONS: The results suggest that combining GTV of
the 3D-CT with the ITV of the MIP is more accurate than the ITV of the MIP alone,
and thus would be a simple method to reduce breathing irregularity induced errors
in ITV delineation for treatment planning of lung cancer.
PMID- 28519025
TI - SU-E-J-199: A Novel Method to Evaluate Local Control and Recurrence Using 18F-FDG
PET After Lung SBRT.
AB - PURPOSE: The goal of this study is to evaluate the predictability of a novel
method using a self background-corrected maximum Standard Uptake Value (cSUVmax)
from 18F-FDG Positron Emission Tomography (PET) of the patients following lung
cancer stereotactic body radiosurgery (SBRT). METHODS: 20 qualified patients
treated out of 38 patients treated with SBRT for a single lung malignant lesion
between May 2009 and December 2009 were enrolled in the cohort study. All had pre
and at least one post-treatment PET images available at the time of study. The
mean normal tissue SUV from the descending aorta was sampled as baseline to
divide SUVmax of tumor site. The resultant cSUVmax was used for assess the local
control or possible recurrence. The Result was then compared with that using
SUVmax alone method. RESULTS: The average follow-up length was 48.9 weeks ranging
from 18.6 to 115.0 weeks. The mean SUV of aorta was measured as 1.821+/-0.364,
ranging from 1.173 to 2.576. From the pre-treatment PET, 70% and 65% was
indicated positive correspondingly when using SUVmax with 2.50 and cSUVmax with
1.52 thresholds. When PET was taken < 29 weeks post-SBRT, 75% and 67%
respectively showed higher values in the locally controlled group. For PET = 29
weeks after SBRT, with cSUVmax both locally controlled and recurrent groups are
accurately identified, while SUVmax shows 5% false positive and one possible
false negative. CONCLUSIONS: The SUVmax in lung tumor site corrected by the mean
SUV of descending aorta or cSUVmax provided a more reliable parameter than using
SUVmax alone in predicting the local control and recurrence for follow-up PET of
patients after lung SBRT. The method used in this study objectively displayed a
strong correlation between low cSUVmax and local control following lung SBRT in
this investigation, otherwise a local recurrence is suggested.
PMID- 28519026
TI - SU-E-T-25: Real Time Simulator for Designing Electron Dual Scattering Foil
Systems.
AB - PURPOSE: To create a user friendly, accurate, real time computer simulator to
facilitate the design of dual foil scattering systems for electron beams on
radiotherapy accelerators. The simulator should allow for a relatively quick,
initial design that can be refined and verified with subsequent Monte Carlo (MC)
calculations and measurements. METHODS: The simulator consists of an analytical
algorithm for calculating electron fluence and a graphical user interface (GUI)
C++ program. The algorithm predicts electron fluence using Fermi-Eyges multiple
Coulomb scattering theory with a refined Moliere formalism for scattering powers.
The simulator also estimates central-axis x-ray dose contamination from the dual
foil system. Once the geometry of the beamline is specified, the simulator allows
the user to continuously vary primary scattering foil material and thickness,
secondary scattering foil material and Gaussian shape (thickness and sigma), and
beam energy. The beam profile and x-ray contamination are displayed in real time.
RESULTS: The simulator was tuned by comparison of off-axis electron fluence
profiles with those calculated using EGSnrc MC. Over the energy range 7-20 MeV
and using present foils on the Elekta radiotherapy accelerator, the simulator
profiles agreed to within 2% of MC profiles from within 20 cm of the central
axis. The x-ray contamination predictions matched measured data to within 0.6%.
The calculation time was approximately 100 ms using a single processor, which
allows for real-time variation of foil parameters using sliding bars.
CONCLUSIONS: A real time dual scattering foil system simulator has been
developed. The tool has been useful in a project to redesign an electron dual
scattering foil system for one of our radiotherapy accelerators. The simulator
has also been useful as an instructional tool for our medical physics graduate
students.
PMID- 28519027
TI - SU-E-J-211: Development of Respiratory Training System Using Individual
Characteristic Guiding Waveform.
AB - PURPOSE: The purpose of this study is to develop the respiratory training system
using individual characteristic guiding waveform to reduce the impact of
respiratory motion that causes artifact in radiation therapy. METHODS:
Respiratory training system was developed by LabView (National Instruments,
version 8.6). The real-time respiratory signals were acquired using in-house
developed belt type sensor and more user-comfortable HMD was used for visual
guiding (Vuzix, Wrap 920). The respiratory training program consists of three
main components. It is (1) respiratory signal reading and peak detection program
(2) individual characteristic guiding waveform generation program (3) respiratory
signals acquisition and visual guiding program. In order to evaluate the
feasibility of in-house developed respiratory training system, 5 volunteers were
included and their respiratory signals were acquired using the in-house developed
belt-type sensor. Respiratory training system needs 10 free breathing cycles of
each volunteer to make individual characteristic guiding waveform based on
Fourier series and it guides patient's next breathing. For each volunteer, free
breathing and guided breathing which uses individual characteristic guiding
waveform were performed to acquire the respiratory cycles for 3 min. The root
mean square error (RMSE) was computed to analyze improvement of respiratory
regularity in period and displacement. RESULTS: It was found that respiratory
regularity was improved by using respiratory training system. RMSE of guided
breathing decreased up to 40% in displacement and 76% in period compared with
free breathing. The average of RMSE was decreases from 0.012V to 0.008V in
displacement and from 0.432 sec to 0.192 sec in period. CONCLUSIONS: In
conclusion, since the guiding waveform was easy to follow for the volunteers, The
respiratory regularity was significantly improved by using in-house developed
respiratory training system. So it would be helpful to improve accuracy and
efficiency during 4D-RT, 4D-CT.
PMID- 28519028
TI - SU-E-J-181: Explore the Value of 18F-FDG, PET and CT Scan for the Clinical Stage
of Esophageal Carcinoma.
AB - PURPOSE: To evaluate the sensitivity, specificity and accuracy of 18F-FDG, PET
and CT were used for T and N stage for esophageal carcinoma, and explore the SUV
value evaluating prognosis of esophageal carcinoma. METHODS: PET and CT scan as
well as T and N stage were carried out for 29 cases of preoperative esophageal
carcinoma patients, those results were analyzed and compared with postoperative
pathological TNM stage. RESULTS: CT scan diagnosis the T stage was obviously
higher than PET in term of determining T staging, while PET scan diagnosis the N
stage was higher than CT, but there was no significantly difference. It was clear
that only the Kappa value of preoperative PET scan in T stage was poor (Kappa
value, 0.4), the Kappa values for PET scan in N stage, as well as preoperative CT
scan in T and N stage were good (Kappa value.0.4). The SUV values were increasing
with the lesion volume and length of PETsuv2.5 becoming bigger. The survival was
better when patients with SUV value, 9.0 than those with SUV value=9.0.
CONCLUSIONS: CT was better than PET in term of determining clinical T stage of
esophageal carcinoma, while PET diagnosis the N stage was good the same as CT.
SUV 9.0 may be regarded as a practical indexes to determine prognosis in
esophageal carcinoma.
PMID- 28519029
TI - SU-E-T-08: Simple Governing Equations for Tumor Growth.
AB - PURPOSE: To derive a set of simple differential equations, which can represent
temporal growth of typical tumors, by taking into account the effects of the
tumor microenvironment on cell proliferation. METHODS: Cause-effect relationships
between cell proliferation and nutrients contained in blood stream, which
included oxygen and glucose, were modeled. By formulating a set of rate equations
and simplifying those, we finally obtained two differential equations. One
equation represents the change of the tumor mass and included time-varying growth
rate, which was a solution of another equation relating the growth rate with the
blood volume in the tumor. The set of differential equations were numerically
solved by varying a parameter, kappa, which represented the growth rate of the
blood volume relative to the tumor mass. RESULTS: Through numerical experiments
we showed that the tumor volume increased exponentially if the blood volume
increased at the same rate as the tumor. However, the blood volume did not
increase rapidly enough as the tumor grew, the tumor showed the saturation in the
growth when the tumor grew by 1000-fold. Such a retardation of tumor growth was
experimentally observed and the function representing the growth curve is called
as Gompertz equation. One of solutions also showed that the tumor stopped growing
when the blood supply was shut off (or kappa = 0). CONCLUSIONS: A solution of
simple differential equations derived in this study could reproduce the tumor
growth which can be represented by the well known Gompertz equation. Using these
equations we were able to theoretically show that the saturation of tumor growth
observed often for larger tumors could be explained by a relative lack of blood
supply which leads to a decrease in the cell proliferation rate. In a future
study the effects of radiation on the tumor growth will be included in the model.
PMID- 28519030
TI - SU-E-J-192: Static Breath-Hold MRI Based Measurement of Change in Pulmonary
Function Following a Course of Radiation Therapy.
AB - PURPOSE: Radiation Therapy (RT) induced pulmonary function change may depend on
the location, underlying function of that lung prior to radiations, radiation
dose/fractionation and other factors. We propose to evaluate the radiation
induced pulmonary function change using static breath-hold MRI scans with
vascular information and 3D deformable image registration which can provide
pulmonary function relative to RT dose on a regional basis. METHODS: A MRI scan
pair near the end of inhale and near the end of exhale with breath hold were
acquired for one lung cancer patient before RT and 6 months after RT. The patient
was treated with SBRT with 55 Gy to PTVs in the right and the left lung
respectively. B-spline based vesselness preserving image registration algorithm
was applied to register the MRI pair for the calculation of local lung expansion
as a measurement of regional pulmonary function (PF). The PF maps before RT and
after RT were then mapped to the planning CT using the same algorithm tuned for
MRI-CT registration. The pulmonary function change was calculated via the PF
ratio between two MRI pairs. RESULTS: Strong spatial correlation was found
between the irradiated lung region and the region with greatly decreased PF.
Based on dose and PFC distribution, no strong determinant factor was found for PF
lost in the left lung while the right lung shows that all the lung tissue
receiving dose larger than 28 Gy will have a decreased PF. CONCLUSIONS: We
demonstrated a method that uses static breath-hold MRI based lung imaging to
evaluate radiation induced pulmonary function change which can be applied to
study the dose and the pulmonary function change in a regional basis. This work
is supported by NIH grant support 1R21CA144063.
PMID- 28519031
TI - SU-E-T-19: Fitting a Multiple Source Photon Model for Monte Carlo Treatment Plan
Verification.
AB - PURPOSE: To assess and reduce the difficulty of fitting a multiple source photon
model for monte carlo treatment plan verification. METHODS: The EGS4 user code
MCSIM, from Fox Chase Cancer Center, was chosen for its support of a multiple
source photon model, of which the point and secondary (extrafocal) photon sources
were utilized. A described method of fitting the secondary source to in-air
output factors was implemented. Additionally, a method to fit the point source to
a single large field dose distribution was explored. The point source fitter
utilizes a database of pre-simulated mono-energetic fanlines to build
distributions from arbitrary spectra. Perturbations are made to fanline spectra
to reduce the errors along them. In this study the energy spectrum for each
fanline has been limited to the log-normal distribution, which reduces the number
of parameters for each to two. RESULTS: It was found that one spectral parameter
could be set to a constant for all fanlines and the other restricted to linearity
with respect to off-axis position. The model matched the outputs and
distributions in non-superficial areas to within 2% for 6MV and 15MV Varian iX
field sizes between 4 and 40 cm. Various types of treatment plans were then
successfully verified, including 3D, VMAT, IMRT, and an iPlan Monte Carlo
stereotactic lung to within 3% (tumor dose). CONCLUSION: With such tools it is
practical for a non-research physicist to fit a two source photon model for the
purpose of monte carlo treatment plan verification. The only commissioning data
needed are in-air output factors, a single large field dose distribution, and the
usual machine parameters provided by LINAC vendors for clinical second check
programs. Even when only photons are simulated and spectra are greatly simplified
it is possible to achieve acceptable results for non-superficial tumors.
Furthermore, this is achieved without proprietary machine specifications.
PMID- 28519032
TI - SU-E-J-204: The Dosimetric Impact of Daily Setup Error and Inter-Fraction
Prostate Motion on the Calculated Treatment Plan for Patients Receiving IMRT
Based Radiation Therapy.
AB - PURPOSE: Evaluate the dosimetric impact of daily setup error and inter-fraction
organ motion on the radiation treatment plan. METHODS: Twelve patients undergoing
definitive IMRT treatments for prostate cancer were evaluated. All patients
underwent fiducial marker placement prior to treatment planning CT scan, and were
treated to a dose of 8100cGy given in 45 fractions. We retrospectively created a
plan for each treatment day that had a shift available. To calculate the dose the
patient would have received with no setup correction, we mathematically 'negated'
the shift by moving the isocenter in the opposite direction of the shift. The
individualized daily plans were combined to generate an overall plan sum. The
dose distribution from these uncorrected plans was compared to the actual
treatment plans. RESULTS: A total of 390 shifts were negated and their
corresponding plans evaluated. The mean isocenter shift based on the location of
the fiducial markers was 3.3+/-6.5mm to the right, 1.6+/-5.1mm posteriorly, and
1.0+/-5.0mm along the caudal direction. The mean D95 dose when setup error was
corrected and uncorrected for the PTV8100 volume was 8089cGy and 7303cGy (p <
0.001) and for prostate volume was 8228cGy and 7844cGy (p < 0.002). The mean V95
values when setup error was corrected and uncorrected for the PTV8100 volume was
99.9% vs. 87.3% (p < 0.0001). At an individual level, the difference in D95 value
approached 1200cGy for the prostate volume and 2000cGy for the PTV8100 volume.
There was no statistically significant difference in the D35 parameter for the
surrounding normal tissue except for the dose received by the right hip and the
penile bulb. CONCLUSION: This work indicates that significant underdosing,
approaching 2000cGy for the PTV8100 volume, can occur as a Result of inaccurate
patient setup, and emphasizes the importance of accurate patient setup and target
localization.
PMID- 28519033
TI - SU-E-T-01: Applications of 6MV FFF Photon Beams in Optimizing Radiobiological
Response for Respiratory-Gated Liver SBRT.
AB - PURPOSE: To establish a radiobiological basis for gated stereotactic body
radiotherapy of primary and metastatic liver cancers using volumetric arc
radiotherapy in a flattening filter free (FFF) mode. METHODS: Human cervical
carcinoma, SiHa, non-small cell lung carcinoma, H460, and Chinese hamster V79
cells were irradiated in a water bath with 6MV photons from a Varian TrueBeam
linear accelerator. To establish dose-response and its sensitivity to dose rate
following acute irradiation, doses of 2, 4, 6, 8 and 10 Gy were delivered in FFF
mode at 400 and 1200 MU/min. To investigate whether removal of the flattening
filter affects cell response, doses of 5 and 10 Gy were delivered to SiHa and
H460 cells in FFF and filtered modes at 400 MU/min. Finally, to assess the effect
of protracting dose delivery by gating, a dose of 10 Gy was delivered to SiHa and
H460 cells acutely and also over 15, 30 and 60 min. RESULTS: Dose-response over
doses examined was independent of dose rate in FFF mode. Differences in cell
survival following irradiation in FFF and filtered modes were not significant.
However a significant increase in survival for both H460 and SiHa cells was
observed for 15 min split-dose irradiation compared to acute irradiation but
further increase in irradiation time to 60 min did not affect cell survival.
CONCLUSIONS: Dose rate and presence of a flattening filter showed no effect on
cell survival, however, survival was significantly affected when dose delivery
time was protracted to that typical of conformal field therapy. Volumetric arc
based gated SBRT may be beneficial for tumor cell kill, though the gating window
and duty cycle have to be balanced against the effect of dose delivery
protraction. Research Support (Varian Medical Systems).
PMID- 28519034
TI - SU-E-J-185: 4DCT Geometrical Eigenmode Model for Inter-Fraction Evaluation of
Tumor Regression and Breathing Pattern Changes.
AB - PURPOSE: Evaluate the feasibility of using intra-fractional respiratory dominant
eigenmodes of lung deformation as a method to track inter-fractional tumor
regression and other physiological changes. Geometrical evaluation by dominant
eigenmodes during free-breathing may be implemented as an IGART tool for
assessing inter-fractional non-respiratory anatomical variation. METHODS: Intra
fractional deformable image registration (DIR) is performed on 4DCT scans of lung
cancer patients. Principal component analysis is conducted on a set of 10
deformation vector fields for each patient both with and without a lung mask.
Leave-one-out cross-validation (LOOCV) is used to assess intra-fractional
modeling error among a subset of respiratory phases. The first two dominant
eigenmodes of PCA are compared across patients in axial, sagittal, and coronal
slices. RESULTS: Eigenvalues between the first and second dominant respiratory
modes decay by a factor of ten for all patients. Intra-fractional LOOCV maximum
error is on the order of 1mm inside the lung and 4-6mm for the whole thorax for
all patients using the first two dominant eigenmodes. Eigenvalue decay is fastest
for patients where diaphragm motion is relatively larger in magnitude. The first
two eigenmodes generally demonstrate a strong but smooth superior-inferior motion
component with a lesser lateral and anterior-posterior component, while
subsequent less dominant eigenmodes produce more random directional eigenvector
fields. CONCLUSION: The two first principal components are consistent amongst
patients. Inter-fractional eigenmode comparison may provide a means to track
tumor regression and breathing pattern or physiological changes. We expect that
patients with more dominant diaphragmatic respiration will allow for more
delineated eigenmode classification. Clear dominant eigenmode delineation may
allow subsequent less dominant eigenmodes to be inter-fractionally compared as a
means to evaluate and compensate for tumor regression.
PMID- 28519035
TI - SU-E-T-12: Radiation Detector Responses to Applied Homogeneous Transverse and
Parallel Magnetic Fields.
AB - PURPOSE: To determine the relative dose response of a diamond detector and a ion
chamber in a clinical photon beam within uniform magnetic fields, endeavoring to
evaluate and refine reference dosimetry techniques for use in integrated MR-linac
systems. METHODS: The Monte Carlo code PENELOPE was used to model the structure
and materials of the PTW60003 diamond detector and PR06 ion chamber in a 6MV beam
in the presence of a homogeneous magnetic field. The magnetic field strength was
varied from 0 to 1.5T, and both the parallel and transverse magnetic field
orientations with respect to the beam central axis were simulated. The long axes
of the detectors were oriented both perpendicular and parallel to the radiation
beam direction for each magnetic field orientation. All simulations determined
the detectors' signal in air. A small electromagnet was used to experimentally
determine the detectors' response in transverse magnetic fields up to 0.2T to
validate the simulations. RESULTS: The simulated response of both detectors
matched to the experimental data within the estimation error. The relative
response of PR06 and diamond detector varied up to +/-8.5% (depending on chamber
orientation) and >9% respectively with increasing transverse magnetic field
strength. In contrast, both detectors were found to be relatively insensitive to
the increasing magnetic fields irrespective of the detector orientation in
parallel magnetic field. A maximum change of 2% in PR06 response was observed at
1.5T parallel magnetic field and in the parallel orientation of chamber.
CONCLUSION: This work has significant impact on dosimetry protocols for
integrated MR-linac systems, where detector response may be altered by the
presence of a magnetic field. The need for a magnetic field dependent correction
factor is strongly indicated for the transverse magnetic field cases, while such
changes in detector response can be largely ignored in parallel magnetic fields <
1T. CIHR (Canadian Institutes of Health Research) - funding support Faculty of
Medicine and Dentistry, University of Alberta - funding support.
PMID- 28519036
TI - SU-E-J-196: In-Vivo Tumor Blood-Oxygen Content Measurement via Interstitial
Optical Transmission Spectroscopy.
AB - PURPOSE: To demonstrate the application of in-vivo diffuse optical transmission
spectroscopy in quantifying oxygen saturation in interstitial tissue, and to use
this technique to examine reoxygenation dynamics in real-time as tumors responds
to radiotherapy. METHODS: Two 200 micron core fiber optics were threaded through
two 21 gauge hypodermic needles: one coupled to an OceanOptics QE65000
spectrometer, and the other to an Ocean Optics HL-2000-HP 20W light source. These
needles were fixed approximately 3 mm apart, and inserted into nude mice with
human head- and-neck tumor xenografts. The oxygen saturation was then measured as
a function of time after irradiation at intervals of 0.5, 1, 2, 6, 12, and 24, to
measure the tumors' prompt oxygen saturation response to radiation. RESULTS:
Blood volume, deoxy and oxy-hemoglobin concentrations were measured through least
squares fitting of transmission spectra. Furthermore, various configurations of
interstitial fiber optic probes were explored to optimize signal strength.
Improvement of the optical coupling to the biological system and a concurrent
increase in source intensity are the main two focuses for boosting signal
strength. CONCLUSIONS: This work has the potential to give an understanding of
the time-scales of hypoxia and reoxygenation in vivo as tumors respond to
radiation injury. This technique is of particular interest for hypofractionated
therapies particularly treatments of only two or three treatments, where
optimizing treatment timing can increase the tumorcidal effect of the remaining
fractions.
PMID- 28519038
TI - SU-E-T-05: Comparing DNA Strand Break Yields for Photons under Different
Irradiation Conditions with Geant4-DNA.
AB - PURPOSE: To validate and scrutinize published DNA strand break data with Geant4
DNA and a probabilistic model. To study the impact of source size, electronic
equilibrium and secondary electron tracking cutoff on direct relative biological
effectiveness (DRBE). METHODS: Geant4 (v4.9.5) was used to simulate a cylindrical
region of interest (ROI) with r = 15 nm and length = 1.05 mm, in a slab of liquid
water of 1.06 g/cm3 density. The ROI was irradiated with mono-energetic photons,
with a uniformly distributed volumetric isotropic source (0.28, 1.5 keV) or a
plane beam (0.662, 1.25 MeV), of variable size. Electrons were tracked down to 50
or 10 eV, with G4-DNA processes and energy transfer greater than 10.79 eV was
scored. Based on volume ratios, each scored event had a 0.0388 probability of
happening on either DNA helix (break). Clusters of at least one break on each DNA
helix within 3.4 nm were found using a DBSCAN algorithm and categorized as double
strand breaks (DSB). All other events were categorized as single strand breaks
(SSB). RESULTS: Geant4-DNA is able to reproduce strand break yields previously
published. Homogeneous irradiation conditions should be present throughout the
ROI for DRBE comparisons. SSB yields seem slightly dependent on the primary
photon energy. DRBEs show a significant increasing trend for lower energy
incident photons. A lower electron cutoff produces higher SSB yields, but
decreases the SSB/DSB yields ratio. The probabilistic and geometrical DNA models
can predict equivalent results. CONCLUSIONS: Using Geant4, we were able to
reproduce previously published results on the direct strand break yields of
photon and study the importance of irradiation conditions. We also show an
ascending trend for DRBE with lower incident photon energies. A probabilistic
model coupled with track structure analysis can be used to simulate strand break
yields. NSERC, CIHR.
PMID- 28519037
TI - SU-E-J-208: Dosimetric Assessment of Treatment Using CBCT Images.
AB - PURPOSE: To evaluate target coverage for five breast patients receiving boost
treatment to the tumor bed by calculating the daily dose on cone beam computed
tomography (CBCT) images and utilizing deformable image registration techniques.
METHODS: The daily dose is calculated on pretreatment CBCT images using the same
beam configuration as the original volumetric modulated arc therapy (VMAT) plan.
Calculations were done with two different isocenter positions according to: (1)
the initial patient setup and (2) the shifts applied for treatment based on CBCT
verification. The daily doses are deformed and accumulated onto the planning CT
using commercially available deformable image registration software. The dose
distribution is compared to the original distribution and tumor and PTV coverage
is evaluated for both situations (initial and shifted positions). The deformation
accuracy is evaluated by calculating the change in centroid location and the Dice
coefficient of deformed contours. RESULTS: The tumor bed is adequately covered
regardless of the treatment position. The average dose received by 98% (D98) of
the tumor bed volume differs from the original plan by +1.6% and -0.2% for the
shifted and initial positions respectively. However, when dose is accumulated in
the initial setup position PTV coverage is lost; the average D98 for the PTV
changes by -15.8% and -26.9% for the shifted and initial positions respectively.
The average change in centroid location is 0.43 mm and 1.53 mm for the left and
right lung contour respectively. The Dice coefficient for the left and right lung
is 0.94 and 0.95 respectively. CONCLUSIONS: The margins used to define the PTV
are sufficient to ensure tumor bed coverage for the given positioning
variability. We are also confident in the deformation used to deform and
accumulate dose based on deformed contour comparison. Hardware provided by MIM
Software Inc.
PMID- 28519039
TI - SU-E-J-210: Lung Tumor Target Volume Contours on EPID Cine Mode Images.
AB - PURPOSE: While real time imaging of treatment through an electronic portal
imaging device (EPID) is a powerful tool to monitor treatment, limited field of
view and lower contrast from an MV beam can make assessment difficult for
physicians. This work will develops a method to register and project contour
outlines for the internal target volume (ITV) and planning target volume (PTV) of
lung tumor cases onto cine mode EPID images to help physicians in interpretation
during treatment. METHODS: A sequence of EPID images, acquired during treatment,
was registered to treatment planning computed tomography (CT) by machine geometry
and patient setup with cone-beam computed tomography (CBCT). The planning CT was
converted from Hounsfield scale to electron density by calibration curves of our
CT simulator and digitally reconstructed radiographs (DRRs) were produced to
match the EPID geometry, pixel for pixel. ITV and PTV structures as defined on
the planning CT were then projected onto the DRRs. The DRRs were registered to
the EPID images using cross correlation of a single template defined within the
treatment aperture of each image. Once registered, the contours from the DRR were
transferred to the EPID. RESULTS: We were able to successfully register MV DRRs
to EPID images and display the projected target volumes. Without introduced
motion, geometric registration and CBCT guided patient setup up were sufficient
to register the contours within a single pixel, as normalized cross correlations
produced no additional shift. We expect the DRR/EPID registration to be an
important step when looking at cases with substantial tumor movement.
CONCLUSIONS: The visualization of target volumes provides a tool for physicians
to interpret EPID images and assess treatment, especially in cases with tumor
movement. The methods developed will serve as the basis for a clinical tool
providing real time contours.
PMID- 28519040
TI - SU-E-T-07: Edema Induced Changes in Tumor Cell Survival Fraction and Tumor
Control Probability in 131Cs Permanent Prostate Implant Patients.
AB - PURPOSE: The purpose of this study is to estimate the effect of edema, developed
during implant procedure, on tumor cell surviving fraction(SF) and tumor control
probability(TCP) in the patients of prostate cancer who underwent 131 Cs
permanent seed implants. METHODS: The impact of edema on SF and TCP, was
calculated using LQ equation extended to account for exponential nature of edema
decay, dose delivered to dematous prostate and inhomogeneous dose distribution.
Where (1) S(D)=(1/V)Sigmai=1n [Vpi{1+M0 exp(-lambdae t)}Si (D)] Si (D)=exp[
alphaRi (0)?0t [exp(- lambdat)/{1+M0 exp(-lambdae t)}tau/3]dt -betaq(t){Ri (0)?0t
[exp(-lambdat)/{1+M0 exp(-lambdae t)}tau/3]dt }2 ] and (2) TCP=exp[-rhoVpS(D)]
Following parameters, alpha=0.15Gy-1 , beta=0.05Gy-2 , alpha/beta=3.0Gy,
Tp=42days, MU=61.6d-1 and rho=1*106 are used to calculate SF and TCP for 31
patients of 131 Cs permanent seed implants for edema half lives(EHL) ranging from
4 days to 34 days and for edemas of magnitudes(M0 ) varying from 5% to 60% of the
actual prostate volume. RESULTS: The dose reductions in 131 Cs implants varied
from 1.1% (for EHL=4 days and M0 =5%) to 32.3% (for EHL= 34 days and M0 = 60%).
These are higher than the dose reduction in 125 I implants, which vary from 0.3%
(for EHL= 4 days and M0 = 5%) to 17.5% (for EHL= 34 days and M0 = 60%). As edema
half life increased from 4 days to 34 days and edema magnitude increased from 5%
to 60% the SF increased by 4.57 log, and the TCP decreased by 0.80. CONCLUSIONS:
Compensation of edema induced increase in the SF and decrease in the TCP in 131
Cs seed implants should be carefully done by redefining seed positions with the
guidance of post needle plans. The presented model in this study can be used to
estimate the SF or the TCP for pre plan or real time permanent prostate implants
using day 0 post implant CT images.
PMID- 28519041
TI - SU-E-J-191: A Multivariate Framework for N-Tissue Classification in Treatment
Assessment of Glioblastomas.
AB - PURPOSE: Glioblastoma is the most common primary brain tumor in adults and is
rapidly fatal. Treatment monitoring of these patients has increased awareness
that many patients have new areas of contrast enhancement without progressive
clinical signs and symptoms. Although the enhancing areas mimic tumor
progression, the lesions result from treatment effects and subsequently stabilize
or improve without further treatment and are not correlated with poorer outcomes.
This phenomenon has been termed pseudoprogression and is hypothesized to occur
secondarily to edema and vessel permeability in the tumor area as a result of the
combined effects of radiation and chemotherapy. Since the new enhancing lesions
of pseudoprogression are indistinguishable from true disease progression, there
is a need for a predictive model to distinguish the two phenomena. METHOD: We
developed a classification algorithm that combines perfusion and diffusion MRI
imaging to effectively partition the cases as one exhibiting true or pseudo
progression based on a vector of features containing T1, rCBV and ADC imaging.
The multi-sequence classification algorithm uses an expectation maximization (EM)
algorithm that learns from training cases with known clinical outcome to assigns
each voxel to a type of tissue. RESULTS: A training set of 20 where the clinical
outcome is known from biopsy or from long-term follow-up was used by EM algorithm
to model typical imaging values within tissue of pseudo, tumor, edema, necrosis,
vessels or brain anatomy to construct a database of expected values for each
tissue type. When presented with a new case, the algorithm automatically
classifies voxels by their geographical proximities and Mahalanobis distance to
the pre-sampled values. CONCLUSION: Usage of advanced classification techniques
allows automated labeling of voxels into normal, pseudoprogression or tumoral
tissue types. The technique allows for early detection of pseudo progression to
spare patients from unnecessary surgery or toxic chemotherapy.
PMID- 28519042
TI - SU-E-T-18: Output Dependence on Dose Rate for Uniform Scanning Proton Beams.
AB - PURPOSE: Accurate determination of proton output is critical to ensure accurate
proton dose delivery. It was found that the proton output factor was decreased
when the dose rate was low. The purpose of the study is to investigate the dose
rate effects on proton dose output factors. METHODS: We systematically measured
output (nC/MU) of the proton beam as a function of dose rate for various beam
conditions. We first measured dose rate effects for proton beams of three range
and modulation combinations: range 16 cm and modulation 10 cm, range 5 cm and
modulation 3 cm, and range 30 and modulation 15 cm. We then investigated the dose
rate effects for two scanning field sizes, the standard 18*18 cm2 and the largest
available 25*25 cm2. RESULTS: The output factor varied with dose rate, increasing
more than 6% when the dose rate increased from 0.1 Gy /minutes to about 2.5
Gy/minute. The output variation on dose rate seems to depend on only the dose
rate itself. The effect of proton energy and scanning field size on the dose rate
dependence was minimal. CONCLUSIONS: The proton dose output factor depends on the
dose rate at our facility, and can be large (>5%). This dependence needs to be
taken account in output modeling for more accurate proton dose delivery.
PMID- 28519043
TI - SU-E-J-203: Determination of PTV Margin for Lung Tumor Using In-Treatment 4D
CBCT.
AB - PURPOSE: To determine a planning target volume (PTV) margin for lung cancer
patients using a four-dimensional cone-beam CT (4D CBCT) acquired during
volumetric modulated arc therapy (VMAT) treatment. METHODS: A VMAT plan for lung
cancer patients was created by Pinnacle v9.0 (Philips) treatment planning system
(TPS), where the gross target volume (GTVs) in each breathing phase was
delineated by using 4D-planning CT scan (TOSHIBA and ANZAI). The VMAT treatment
was performed with a stereotactic body frame after the registration using Elekta
X-ray volume imaging (XVI) unit. Simultaneous cone-beam projection images were
acquired for 3 or 4 fractions of 10 patients. The in-treatment 4D CBCT was
reconstructed by dividing into four breathing phase bins. A total of 38 in
treatment 4D-CBCT sets were exported to Pinnacle TPS. The isocenter of in
treatment 4D CBCT was matched with that of 4D-planning CT. The tumor motion
during treatment was manually tracked on in-treatment 4D CBCT, and the center-of
mass (COM) location of the tumor was estimated. Analyzing the tumor regions
observed by in-treatment 4D CBCT, a PTV margin in our system was derived.
RESULTS: The average difference in COM location of the tumor was less than 1mm
for all directions, while the standard deviations (SD's) were about 1.3mm, 1.6mm,
and 2.1mm for the lateral, the vertical, and the longitudinal directions,
respectively. The large discrepancy more than 3mm was observed for one patient.
The required PTV margin was about 3-4mm for the lateral and the vertical
directions, whereas it was about 5mm for the longitudinal direction. CONCLUSIONS:
The uncertainties of the tumor motion caused by respiration were observed by in
treatment 4D CBCT images. It was feasible to determine the PTV margin from 4D
volume images. K. Nakagawa receives research funding from Elekta.
PMID- 28519044
TI - SU-E-J-214: Target Intrafraction Motion Dosimetric Impact on 5-Fraction Proton
Prostate SBRT.
AB - PURPOSE: To investigate dosimetric impact of prostate intra-fraction motion to
five fraction hypofractionated proton treatment with uniform scanning (US) and
double scattering (DS) techniques using real-time prostate tracking data from
electromagnetic transponder system. METHODS: Prostate intra-fraction motion can
have spatiotemporal interplay with proton treatment delivery. Five fraction
(7.25Gy/fraction) prostate proton stereotactic body radiotherapy (SBRT)
treatments were simulated for total 14 patients using in-house proton treatment
simulation program. The US treatment was simulated by rigidly moving CTV through
a series of temporal-spatial dose matrices indexed by energy layers, according to
prostate motion traces. The CTV temporal doses of the whole treatment fraction
were obtained and summed as final prostate CTV dose. The DS treatment was
simulated by moving CTV through the energy layer summed dose matrix. For all
patients, the fraction doses and the total dose to the CTV were presented for
both DS and US treatments. RESULTS: The CTV dose of different fractions indicated
that its dose degradation depends on magnitude and direction of prostate intra
fraction motion and is patient specific. For one of the prostate motion traces
investigated, only 70% of CTV received 100% prescribed dose for a simulated US
treatment and 79% CTV had 100% dose for a DS treatment. Furthermore, DVH and
isodose graphs of both treatments revealed that intra-fraction motion caused
significant CTV cold and hot spots in US treatment whereas only cause CTV
underdose in DS treatment. CONCLUSIONS: Intra-fraction prostate motion causes
dose uncertainty to CTV. In the 5 fraction prostate SBRT, prostate intra-fraction
motion causes significant target dose degradation. In US treatment,
spatiotemporal interplay between energy layers delivery and prostate motion leads
to hot and cold spots in CTV for some patients with severe prostate intra
fraction motion. Further investigation of intra-fraction motion management and
its impact on CTV dose is necessary.
PMID- 28519045
TI - SU-E-J-184: Liver Dose Calculation for 90Y Radioembolization with PET/CT.
AB - PURPOSE: 90Y radioembolization is a promising treatment for unresectable
hepatocellular carcinoma. A dose of 120 Gy is typically prescribed to a segment
or lobe of the liver, but dose of 90Y in the liver tumor is highly heterogeneous.
Recently developed 90Y PET/CT enables the visualization of the injected 90Y
distribution with high resolution. The purpose of this study is to develop an
integrated system to quantify 3D dose distribution using PET/CT images. METHODS:
According to our institution's protocol, 90Y PET/CT scan is acquired for each
patient two hours after radioembolization. Based on the 90Y activity distribution
from PET scans, we used a convolution method to calculate radiation dose with a
published dose kernel for 90Y. The gross tumor volume (GTV) was retrospectively
contoured by a clinician using contrast-enhanced diagnostic CTs. Because of
breathing motion and different patient positions between the diagnostic CT and
PET/CT, we manually registered these two CT scans by aligning 200 Gy dose line
with the center of the intended treatment GTV. RESULTS: The system was integrated
with a commercial RT PACS/Review station (MIMVista) through DICOM. The dose
obtained was of the resolution of PET scans (2-4 mm). This distribution enables
physicians to quantify treatment volume and dose relationships either through 3D
dose distributions or dose volume histograms. For the five patients tested for
our program, liver mean doses agree with clinical results within 5%. We were able
to quantify radiation doses to 95% of GTV, and radiation dose received by the
CTVs extended 5 mm from the GTV. CONCLUSIONS: The system is easy to use for
radiation oncologists. With this system, clinicians can quantitatively evaluate
delivered dose of 90Y treatment in high resolution. No conflict of interest for
this work.
PMID- 28519046
TI - SU-E-T-11: LINAC Dose Profiling Using Cherenkov Emission Imaging.
AB - PURPOSE: To demonstrate the potential for fast 3D dose profile imaging of a LINAC
beam using images of the induced Cherenkov radiation in a water tank. A
specialized time-gated imaging system was developed as a prototype to quantify
and compare with Monte Carlo, to illustrate the concept. METHODS: Images were
acquired from a water tank during irradiation from a 6 MV Varian-2100C linear
accelerator beam using a time-gated CCD-based imaging system. The camera was
placed normal to the tank wall to minimize parallax reflections, and resultant
images were produced by evaluating the median of each pixel in a stack of 2000
images taken at a rate of 60 Hz with an exposure time of 10 ms. Experimental data
was compared to images obtained from GEANT4 simulations of the optical setup.
RESULTS: Examination of the scored quantities for dose and generated Cherenkov
photons indicates that there is a strong similarity, which can be explained by
considering the electron energy losses per unit path length. However, due to the
complex convolution of the Cherenkov emission directionality and camera lens
angular field of view, this relationship is distorted. These errors can be
calibrated using the GEANT4 simulations to more accurately reflect the intrinsic
dose in the water volume. CONCLUSIONS: This work demonstrates dose profiling
using the induced Cherenkov radiation signal for the first time. These
preliminary results serve as a proof of concept of imaging at one azimuthal
angle. Analogous to SPECT, the technique could easily be translated to multiple
angles yielding full dose reconstructions following filtered back projection.
Further refinement of this technology could be the first step in a paradigm shift
towards an alternative method for fast radiation field analysis. Advantages would
include increased speed, as well as the ability to profile dynamic beam shapes
within transparent solid anthropomorphic phantoms. This work has been financially
supported by NIH grant R01CA109558.
PMID- 28519047
TI - SU-E-J-195: Dosimetric Consequences of Metal Prosthesis in Prostate 3D CRT by
Using Monte Carlo Dose Calculation Method.
AB - PURPOSE: To investigate dosimetric consequences of patient metal prosthesis in
prostate radiotherapy, considering the body heterogeneity, metal artifacts,
prostate daily displacements and target delineation. METHODS: Three prostate
patients with metal prosthesis were simulated with CT images and 3D ultrasound
images. Conformal RT treatment plans were generated based on target volumes
delineated on CT images without artifact correction (PTVa). The patients'
treatments were aided with an ultrasound (US) localization system for daily PTV
setup correction. We retrospectively reevaluated the delineation of PTVs by 1)
using simulation CT images artifact-corrected by using an algorithm developed by
M. Bazalova et al (2007) (PTVc) and 2) using the 3D ultrasound simulation images
as guide (PTVus). Daily setup corrections to the PTVs were incorporated to
calculate composite delivered dose by using XVMC simulation on the patient
phantom derived from the artifact-corrected CT images. DVHs and dose
distributions for different PTVs were then compared with the reference treatment
plans (XVMC-calculated on the artifact-degraded CT images). RESULTS: The PTVa
volume was the largest, about 1.3% larger than artifact-corrected PTVc and 5.2%
larger than PTVus. Adapting artifact-corrected CT images can improve the DVH
curves of PTVc and increase the D95% and V95% for PTVc by more than 5% while D50%
and V50% for rectum and bladder are raised by up to 41.6%. DVH analysis on PTVa
and PTVus shows a small difference in the changes of their DVH indices, less than
4% for the studied cases. CONCLUSIONS: The strike artifacts from metal prosthesis
will increase the volume of PTVa, and affect the patient dose calculation.
Original patient plan did not accurately predict the dose degradation. Artifact
correction may be necessary for some cases having severe metal artifacts. Using
US images to help delineating PTV makes a negligible clinical significance.
PMID- 28519048
TI - SU-E-T-22: Is the Residual Range a Universal Quantity to Specify the Quality of
Modulated Proton Beams?
AB - PURPOSE: To investigate the validity of using the residual range as a universal
quantity to specify the quality of modulated proton beams. METHODS: We used TOPAS
(Tool for Particle Simulation), an application of the Geant4 toolkit, to simulate
absorbed dose and stopping-power distributions from a commercial passive
scattering nozzle. We used the standard physics lists from Geant4 in the
simulations. All particles were included, as well as physics models for nuclear
interactions. No variance reduction techniques were used. Dose and averaged
stopping-power as functions of depth were scored in a water box with 320 scoring
volumes of 15 * 15 * 0.1 cm3 . Stopping-power spectra were scored in a15 * 15 *
0.1 cm3 volume located in the middle of SOBPs. All particles were considered in
the dose scoring. Only protons (primary and secondary) were considered in the
scoring of stopping-power. RESULTS: For the same residual range, differences in
averaged stopping-power values of up to 13% were observed for a 200 MeV beam with
modulations of 4 cm and 8 cm, respectively. Simulations of four modulated proton
energies with the same SOBP of 8 cm showed differences of up to 13% in the
averaged stopping-power values even in the SOBP region. We also simulated
stopping power spectra in the middle of 8 cm SOBPs for four modulated proton
energies. The averaged stopping-power values calculated from the spectra were
within 3%, however, their distributions were very different with full width at
half-maximum 150% larger for the 250 MeV beam compared to that of the 140 MeV
beam. CONCLUSION: Large differences in the averaged stopping-power values and
stopping-power spectra were observed for the same residual range. Determining
whether these differences have a significant effect on the response of radiation
detectors exposed to proton beams requires further investigation. Natural
Sciences and Engineering Research Council of Canada and Ontario Graduate
Scholarship Program, Ontario Ministry of Training, Colleges and Universities.
PMID- 28519049
TI - SU-E-J-207: Compensation of Target Distortion of Pancreatic Tumor in Free
Breathing CT Using 4D Contour Propagation.
AB - PURPOSE: Due to lack of soft-tissue contrast, target distortion for the upper
abdomen targets such as pancreatic tumors is complicated and requiring sufficient
remedy. By applying automatic contour propagation, the authors use the
information obtained from 4D CT to test if the deformable image registration
compensates the respiration-induced distortion of pancreatic tumor in free
breathing (FB) CT images. METHODS: Ten patients with unresected pancreatic cancer
treated with either preoperative or definitive chemoradiation were studied.
Pancreas GTVs were delineated on the FB CT. Using deformable image registration,
the FB GTV contours were propagated to each phase of the 4D CT images taken right
after the FB CT, and were compared with the FB GTV to see difference in tumor
volume and tumor size along individual dimensions. A one-dimensional tumor motion
in proportion to cos4(omegat) was simulated to calculate the probability
distribution function for different magnitude of distortions during FB CT scans,
and a binary classification test was conducted to analyze the observed results.
RESULTS: The probability distribution function predicted that four out of the ten
cases would have substantial target distortion given the variation in target
motion amplitudes. Three of these four cases show substantial difference in the
superior-inferior size of FB GTV compared to the average 4D GTV, taking into
account the uncertainties caused by motions perpendicular to the scanning axis
and resolution of the CT scanner. The binary classification test yielded a
precision of 75% and an accuracy of 90%. CONCLUSIONS: Pancreatic GTV distorted
due to respiration-induced tumor motion is effectively compensated by contour
propagation from free-breathing CT to 4D CT using DIR. Union of GTVs of all
breathing phases or IGTV can be genreated from 4D set of GTVs propagated from
that of free breathing. This study is partially supported by NIH grant
1R01CA133539-01A2. I do not have conflict of interest.
PMID- 28519050
TI - SU-E-T-04: Repair Kinetics of Sublethal Damage in Rat Cervical Spinal Cord -
Application of the GLQ Model Incorporating Reciprocal Time Pattern.
AB - PURPOSE: The repair rate conventionally assumed to be constant during the entire
radiation course. However, increasing evidences from animal studies show that the
repair process may slow down with time and the experimental data does not fit an
exponential pattern. To address this enigma, we presented a generalized linear
quadratic (gLQ) model incorporating reciprocal time repair pattern of sublethal
damage and fit the model to published experimental data. METHODS: In the gLQ
model, the parameter G in the surviving fraction represents the repair process of
sublethal damage with Tr as the repair half-time. When a reciprocal time pattern
of repair process was adopted, a generalized form of G was derived analytically
for arbitrary radiation schemes (I(t) = Ii, ti-1 < t < ti, where i=1 to N, Ii is
the dose rate of the ith segment to the voxel in question, and N is the total
number of segments for the entire treatment course). The published animal data
was used to test the reciprocal formulas. RESULTS: The gLQ model incorporating a
reciprocal time pattern to describe the repair process was used to fit the
experimental data. The reciprocal model showed better fit to the animal data than
the exponential model, particularly for the ED50 data, resulting in the following
parameters: the reduced chi-square of 1.52, alpha/beta=0.9 Gy, Tr =1.0 h for the
reciprocal model and reduced chi-square of 3.39, alpha/beta=1.6 Gy, Tr=3.5 h for
the exponential model. CONCLUSIONS: The modeling results suggest that the gLQ
model incorporating the reciprocal time pattern of sublethal damage repair
facilitates the interpretation of complex experimental designs, especially for
irregular dose delivery schedules. These formulas can be used to analyze
experimental and clinical data, where a slowing-down of the repair process occurs
during the radiation therapy course.
PMID- 28519051
TI - SU-E-J-188: Lung CT Density Changes during the Conformal Radiotherapy: A
Prediction for Lung Radiation Pneumonitis.
AB - PURPOSE: Radiologic lung density changes are observed durng radiotherapy for lung
cancer. We studied the relationship between dose and computed tomography (CT)
density changes during the treatment, a prediction for lung radiation
pneumonitis. METHODS: 30 Stage a...c lung cancer patients with CRT were thirty
fractions of 2.0 Gy, prescribed at the 90% isodose. Follow-up CT scans performed
at less than 3 weeks (n=15) and between 3 and 6 weeks (n=15) after CRT
radiotherapy were reviewed. New CT scans were coregistered with baseline scans
using CT-CT normalized mutual information registration algorithm. Voxel
Hounsfield unit histograms were created for doses between 0.5 and 50 Gy. Linear
mixed effects models were used to assess the effects of CRT dose on CT density,
and the influence of possible confounders was tested. RESULTS: Increased mean CT
density was associated with higher dose, increasing planning target volume size,
and increasing time after CRT (all p <0.05). Density increases were apparent in
areas receiving 20 Gy, but seemed to plateau above 40 Gy. In regions receiving
>30 Gy, the reduction in air-filled fraction of lung during treatment was up to
20%. No increase in CT density was observed in the contralateral lung receiving
less than 5 Gy. CONCLUSIONS: A dose-response relationship seems to exist for
quantitative CT density changes during CRT radiotherapy. The density between old
and new CT during the treatment could be a prediction for lung injury.
PMID- 28519052
TI - SU-E-T-15: Small and Nonstandard Photon Field Dosimetry Characterization Using
Monte Carlo Methods.
AB - PURPOSE: To quantify uncertainty reduction in small photon field dosimetry
through characterization of ionization chambers and calibration conditions using
detailed Monte Carlo methods benchmarked against NIST-traceable measurements.
METHODS: Phase space profiles were obtained using detailed EGSnrc Monte Carlo
models for a Varian 6 MV photon linear accelerator, and a NIST-traceable cobalt
60 teletherapy unit. The responses of a farmer-type ionization chamber, two micro
ionization chambers, and one scanning-type ionization chamber were simulated in
multiple calibration conditions. Calibration conditions included static field
sizes ranging from (10*10) cm squared to (0.5*0.5) cm squared for the 6 MV and
cobalt-60 beam qualities and an additional dynamic IMRT plan for the 6 MV beam
quality. Calibration conditions also consisted of ionization chambers placed in a
standard water phantom and in a specially designed acrylic phantom. Tolerance
limits on the calibration conditions were investigated. All models were
benchmarked against measured beam quality data, including ionization chamber beam
quality correction factors for the standard absorbed dose to water cobalt-60
calibration coefficient. RESULTS: The majority of the simulated small field
response values fell within the uncertainty of the measured values. A database
was created for several proposed small field calibration conditions to provide
comparisons with the Co-60 standard reference conditions. The database includes
the small field calibration conditions' beam quality correction factors,
tolerances, and dose calibration uncertainties. CONCLUSIONS: The characterization
of multiple calibration conditions provided an improved understanding of how the
cobalt-60 ionization chamber absorbed dose to water calibration coefficient from
an ADCL can optimally be applied to small and nonstandard field calibrations to
reduce the associated dose uncertainty. The developed methodology will contribute
to future research of other small field radiotherapy modalities. The resulting
database provides support for future recommendations on the implementation of
small and non-standard field calibration protocols.
PMID- 28519053
TI - SU-E-T-06: A Mathematical Explanation to Tumor's Response to Perfusion and
Hypoxic Fraction after Radiation.
AB - PURPOSE: To develop a dynamic model that explains oxygen dynamics between the
microvascular perfusion and the hypoxic cell population inside a tumor. METHODS:
Bussink et al (Radiat Res 153(4), p.398 (2000)) observed fast oxygen dynamics,
faster than cell-death. Based on a simplified three-compartment-model: the
microvasculature, well-oxygenated, and hypoxic tumor cell populations. We applied
a first-order differential model for the tumor's transient response as a function
of oxygen content within the blood vessels. The sink terms in our model for each
compartment are fast changing parameters because radiation rapidly changes the
oxygen consumption of the tumor cell in a time scale which is much faster than
the population changes of the tumor. Transportation balance condition is also
applied for each compartment. RESULTS: Our simulation results can explain the
experimental data in Bussink et al's (Radiat Res 153(4), p.398 (2000)) paper. We
provide an explanation for the relative complex behavior of the microvascular
perfusion after radiation that emphasizes the role of dynamic metabolic changes
in addition to population changes. CONCLUSIONS: A newly developed dynamic model
leads our understanding to the interrelationship between microvascular oxygen
content within the blood vessels and the hypoxia state of the tumor to a deeper
level, which has the potential to provide the theoretical foundation for the
patient' specific adaptive radiotherapy.
PMID- 28519054
TI - SU-E-J-190: A Possible Non-Typical Measurement in Dynamic Contrast MRI for Brain
Tumor Therapy Response Evaluation.
AB - PURPOSE: Dynamic susceptibility contrast (DSC) MRI technique can be used for
brain tumor therapy response evaluation. However, the typical modeling (Eqs.1) is
sometimes problematic in the vicinity of tumor due possibly to the disrupted
microvascular environment associated with the disease. The example is well
illustrated in Fig.1B, where some MRI time series curves (TSC) keep increasing
beyond the baseline value after some time points, which is theoretically
prohibited in the typical modeling. This behavior is not related to other
systemic error such as motion or system instability, which can be verified by the
steady TSC from a CSF region (Fig.1C).To improve the utility of DSC-MRI even in
the problematic, but highly interested, regions of the brain, the non-complying
TSC was assumed legitimate and its increase rate, linked to the degree of
contrast's leakage, was analyzed. METHODS: DSC-MRI (with manually injected
multihance, 0.2 ml/kg) was applied for high grade brain tumor before and after
radiation therapy. The scan technique was based on T2*-weighted PRESTO
implemented on a Philips 1.5T scanner. The analysis of TSC was performed using an
in-house software developed in MATLAB. RESULTS: The TSCs from several regions of
interest (ROI) were obtained (Fig.1). Before radiation therapy, those from ROIs A
and C increase beyond the baseline after about 60 frame that coincides with the
passage of contrast in other complying TSC. The slope of increasing TSC was
determined as shown in Figs. 1B and 1D. After therapy (Fig 1D), the compliance of
TSC in ROI C to the typical modeling was quite improved and the degree of leakage
shown as slope, as well as the area of leakage (Fig 2), decreased after the
therapy, suggesting the therapy possibly repaired the leakage. CONCLUSION: A non
typical measurement was introduced to improve DSC-MRI's utility in the brain
tumor therapy monitoring. American Cancer Society Institutional Research
Grant/Upstate Cancer Research Institute.
PMID- 28519055
TI - SU-E-T-17: Comparison of MCNP5 Calculations in the Buildup Region with Plane
Parallel Ionization Chamber Measurements for 6 and 18 MV Photon Beams.
AB - PURPOSE: Cylindrical ion chambers are known to overestimate the dose in the
buildup region, where gradients are high. The potential for MCNP5 to produce
accurate calculations in this region, even when benchmarked with a large volume
chamber, was tested. METHODS: MCNP5 was used to model 6 and 18 MV photon beams
for a Varian accelerator using vendor geometry with the collimator corrections of
Chibani and Ma. Modeling was benchmarked by adjusting electron beam energy and
diameter to match calculations with ionization chamber (with 0.125 cm3 sensitive
volume) measurements of percent depth doses (PDDs) beyond dmax and cross dose
profiles for 5*5, 10*10 and 30*30 cm2 field sizes. For comparison in the buildup
region, the MCNP5 voxel was reduced to 1 mm, with extrapolation to find surface
dose. In this region a plane parallel chamber (with 0.055 cm3 sensitive volume)
was used to measure PDDs at 0, 2 and 4 mm depths for the three field sizes, using
the Khan over-response correction. RESULTS: Calculations and cylindrical chamber
measurements for PDDs beyond dmax agree within 2% for all field sizes and
energies. Dose profiles at dmax (1.5 cm and 3.3 cm for 6 and 18 MV) and at 10 cm
agree within 2% in the flat region and within 10% in the penumbra. In the buildup
region, the MCNP5 calculations agree with plane parallel PDD measurements within
3% at 2 and 4 mm depths. The extrapolation of the MCNP5 PDD overestimates the
surface dose for the 18 MV beam for the 30*30 cm2 field, and is within 4.2% for
the smaller fields and for all field sizes at 6 MV. Improved extrapolation
techniques may yield better surface dose agreement. CONCLUSIONS: Accurate dose in
the buildup region can be calculated by MCNP5.
PMID- 28519056
TI - SU-E-J-202: Treatment Dose Assessment with the Consideration of Radiation Dose
Inducible Organ Shrinkage/Deformation.
AB - PURPOSE: For asymmetric organ shrinkage caused by heterogeneity dose
distribution, tissue elasticity based deformable organ registration cannot be
directly applied to the treatment image to construct the treatment dose. A novel
approach is proposed to include radiation dose inducible organ
shrinkage/deformation in the consideration of treatment dose assessment. METHODS:
A model and algorithm were developed to include dose inducible organ shrinkage in
the deformable image registration. In the model, we assume that the logarithm of
tissue-element volume shrinkage ratio is proportional to the LQ survival
function, and the tissue-element displacement field is the gradient of a scalar
potential function. The derived Poisson equation of the potential was solved
using a finite element method. Two steps registration was implemented to
determine the tissue-element volume and displacement. The first is the
conventional deformable image registration to determine the organ surface. The
second is to map the element volume/position in the shrinking organ with using
the dose inducible shrinkage model. Treatment dose was constructed by applying
both the conventional deformable registration and the shrinkage model on CBCT
images obtained from h&n treatment. The dose distribution in the patient parotid
was evaluated. RESULTS: Treatment dose-volume, V30, constructed including the
dose inducible parotid shrinkage was 11% higher than the one from the
conventional deformable image registration and dose construction. Tissue elements
in the high dose region shrink more than those in a low dose region which results
in extra tissue elements in the organ move into the high dose area during the
treatment course and an unfavorable dose-volume relationship in the organ.
CONCLUSIONS: Without including dose inducible organ shrinkage, treatment dose in
a shrinking organ could be underestimated. On the other hand, including this
effect in the treatment evaluation and adaptive planning optimization will
minimize the potential detriment of the effect.
PMID- 28519057
TI - SU-E-J-213: Comparison of the Effect of Metal Implants in Three Different
Radiation Therapy Modalities; IMXT, Tomotherapy, and Proton Therapy.
AB - PURPOSE: To compare and evaluate the dosimetric effect of metal implants in 3
different radiation therapy modalities, photon IMRT, Tomotherapy, and Proton
Therapy. METHODS: We have constructed two sets of PMMA phantom with and without
titanium alloy orthopaedic implants embedded. Combinations of the two phantom
sets provide a hole in the middle for a dose measurement using ion chambers and
also a space in which an EBT film can be inserted for a measurement of dose
distribution in that plane. The phantoms have been CT-scanned separately and will
be planned in 3 different treatment modalities (IMXT, Tomotherapy, and Proton
therapy in passive scattering mode). In each plan, we make an assumption that the
beam path(s) should include the metal implants so that we can compare the
dosimetric effect in different modalities directly. The plan comparison between
the three modalities will be made. In addition, point doses and dose
distributions of the plans will be measured using ion chambers and EBT films and
compared to the Result of the plan study. RESULTS: The plan outcome of three
different modalities shows different properties as expected. The uncertainty due
to the presence of high-density metal is not only coming from the metal artifacts
in CT numbers but also coming from the distinct physical property of the metal
especially for the proton therapy. The most suitable treatment modality among the
three treatment methods in various aspects will be detemined. CONCLUSIONS: The
comparison Result would provide a guideline for the selection of radiation
therapy modalities in the presence of metal implants and help to make decisions
based on quantitative supporting data. In addition, the Result would be a basis
for the further study to effectively avoid the undesired effects of the metal
implants in radiation therapy especially for the proton therapy.
PMID- 28519058
TI - SU-E-J-183: Dose Distribution Generated from 131 I Radionuclide Using SPECT-CT.
AB - PURPOSE: 131 I radionuclide therapy is widely performed in a thyroid cancer
treatment, but there has been almost no evaluation of the dose distribution. The
aim of this work is to develop the calculation system using the data of SPECT-CT
and to examine the effects of their image resolutions on the dose distribution.
METHODS: We designed and constructed an acrylic phantom for measurement. A
radioactive iodine capsule and glass dosimeters can be set in the layer structure
of the phantom. We put iodine capsules (37MBq, 111MBq, 185MBq) in the middle of
the phantom and acquired SPECT-CT (Infinia Hawkeye4 (GE)) images. Both the CT
value data (image resolution: 1.1 mm) and the intensity map data of SPECT (image
resolution: 4.4 mm) were independently used for the estimation of the cumulative
dose distribution generated from the radioactive iodine in the phantom. We
adopted Monte Carlo program PHITS2.0 as the simulation of the dose calculation.
The absolute dose was measured by glass dosimeters. RESULTS: The measurement
result by glass dosimeters was very similar to the Monte Carlo simulation result,
in which the difference was about 0.3 %. We obtained the dose distributions
reconstructed by the radioactive iodine distribution using CT value data and
SPECT data, respectively. The iodine distribution from CT could be finer than
that of SPECT data because of its higher image resolution. As a result, the
difference was found to be factor two in the middle of the iodine distribution.
On the other hand, both of the dose distribution was almost same above 2.2 cm
distance from the center. CONCLUSIONS: We can reconstruct the 131I dose
distribution using SPECT-CT data. For more accurate calculation of the dose
distribution, it would be crucial to increase the resolution of SPECT data.
PMID- 28519059
TI - SU-E-T-10: Monte Carlo Study of the Dose Enhancement Factor (DEF) for Gold Nano
Particle (GNP) on the Cellular Level.
AB - PURPOSE: In megavoltage external beam radiotherapy, in vivo cell experiments
suggest GNP could be used as a radiosensitizer by having radiation dose
enhancement factor (DEF) significantly larger than 1. However, Monte Carlo (MC)
simulations published in the literature failed to give prove, in which most of
them only simulated the interactions between the radiation beams and a single
GNP. In this study, we built a multi-GNPs model considering possible spatial
arrangements of GNPs relative to a cell to calculate the DEFs of GNPs. METHODS:
Geant4 MC code with G4DNA physics model which can trace electrons down to eV
level was used. Two types of geometry models representing different GNP-cell
binding were created with each GNP modeled individually: (1) shell model with
GNPs randomly and sparsely distributed in a shell in water mimicking when the
GNPs were binding to the cell membrane, and (2) sphere model with GNPs randomly
and sparsely distributed in a sphere in water mimicking when GNPs were floating
inside the cytoplasm. Photon and electron spectrum at 5 cm in depth in water from
a Varian 6MV beam was used as the radiation source. Dose to water inside the
shell or the sphere representing cytoplasm were scored and compared to situations
without GNPs to calculate the DEF. We also looked into the variation of DEFs due
to different GNP sizes and concentrations. RESULTS: A 35 um water cubic were
successfully built in Geant4 with spatial resolution of 100 nm. Preliminary
results shown under 200 keV electron irradiation, 100 nm GNPs in the shell model
shown increased dose to cell at the beam entrance (DEF = 1.08). CONCLUSIONS: The
computation is undergoing for different GNP sizes and concentrations. Meaningful
results are expected on the completion of this study.
PMID- 28519060
TI - SU-E-J-194: The Impact of Different Imaging Measures on Treatment Response
Assessment of Bone Metastases.
AB - PURPOSE: Several treatment response metrics, such as RECIST and PERCIST, have
been established for assessing individual solid tumors. However, metastatic
prostate cancer poses a unique challenge to these metrics because bone lesions
are often numerous and non-measureable. This study investigated the impact of
using different imaging measures for treatment response assessment in patients
with metastatic prostate cancer. METHODS: Six patients with metastatic prostate
cancer were treated with molecular targeted therapy and received whole body [18
F]NaF PET/CT scans pre-, mid-, and post-treatment. Lesions were segmented using a
threshold of 20% the maximum SUV in bone and then manually adjusted with
physician guidance. For each patient, SUVmax, SUVmean, SUVpeak, SUVtotal, number
of lesions, and total volume of bone lesions were determined. For each measure,
treatment response was calculated as the percent change relative to pre
treatment. The range of the different responses was calculated for each patient
at each response time point. The population average of the patient ranges was
calculated. RESULTS: The patient responses varied greatly for different imaging
measures. The population-averaged range for all response measures was 50%. In
general, SUVmax, SUVmean, and SUVpeak responses were negative, indicating good
response to treatment, but the number of lesions, volume, and SUVtotal responses
were positive, indicating disease progression. When the measures were separated
into these two groups, the population-averaged range was only 25% among the
number of lesions, volume, and SUVtotal responses and 10% among the SUVmax,
SUVmean, and SUVpeak responses. CONCLUSIONS: Several treatment response metrics,
such as RECIST and PERCIST, have been established for assessing individual solid
tumors. However, metastatic prostate cancer poses a unique challenge to these
metrics because bone lesions are often numerous and non-measureable. This study
investigated the impact of using different imaging measures for treatment
response assessment in patients with metastatic prostate cancer.
PMID- 28519062
TI - SU-E-J-206: Are We Treating the Entire Lung Tumor by Contouring ITV on 4DCT MIP?
AB - PURPOSE: To describe a case report of lung radiosurgery in which defining a
target using a maximal intensity projection CT omitted a portion of the target
due to an overlapping projection of the diaphragm. METHODS: A Lung 4DCT was
obtained, and all ten breathing phases from 0% to 90% were reconstructed. The
gating window was set to treat phases 30% to 70%, and the corresponding Maximum
Intensity Projection (MIP) was generated. An ITV was contoured on the MIP. Tumor
GTVs were contoured on all phases. Another ITV was generated by using the
overlapped projection of all GTVs in the gating window when suspicion arose that
part of the target was omitted. The volumes of the ITVs and GTVs were calculated.
DVHs were analyzed on the plan generated to cover the MIP ITV. RESULTS: The
initial ITV based on the MIP omitted 15% of the target Since the ITVs of the
diaphragm and the tumor overlap in the MIP, and the imaging technique cannot
differentiate them, contouring tumor only on MIP has risk of missing part of the
tumor. We have also found that the volumes of all 10 phases fluctuate with a
standard deviation of 5.6%. This indicates the imperfection of 4DCT generation.
If the treatment plan was generated based on MIP ITV, DVH shows the lack of
coverage for the true ITV. CONCLUSIONS: We propose two methods to accurately
delineate tumor ITV from 4DCT for cases in which the target is located adjacent
to diaphragm. If it is desired to start with contouring ITV on MIP, thorough QA
needs to be done by going through all gating phases to adjust the ITV
accordingly. A more straightforward method is to contour the GTV on all gating
phases and use the overlapped projections as the ITV.
PMID- 28519061
TI - SU-E-T-21: Modeling a MLC Scatter Source for In-Air Output Factors.
AB - PURPOSE: Scattered radiation from multi-leaf collimators (MLCs) is no longer
negligible for calculating in-air output ratio, Sc for small and irregular fields
often used in intensity-modulated radiation therapy (IMRT). An extra-focal source
model for scattered radiation from MLCs, namely MLC scatter source, has been
developed to improve the accuracy of the Sc calculation. METHODS: A conventional
dual-source model was made by using Sc data that were measured for collimator
defined fields of Varian Clinac IX linear accelerator. Then, an MLC scatter
source at the center of the MLC position of the linear accelerator was assumed in
the model. The MLC scatter source model consisted of two Gaussian functions of
which parameters were iteratively optimized against the Sc data measured for
different MLC fields with fixed collimator sizes. To evaluate the effectiveness
of the developed source model, measurements were made for various MLC-defined
irregular or square fields. The calculated Sc data by using (1) the developed
source model and (2) the conventional dual source model were compared with the
measured data. RESULTS: The mean discrepancy between the measured Sc and
calculated Sc from the developed source model was 0.08+-0.28%, while one from the
conventional source model was 0.44+-0.39%. CONCLUSIONS: The developed MLC scatter
source model in conjunction with the dual source model could improve the accuracy
of the Sc calculation in IMRT fields.
PMID- 28519063
TI - SU-E-T-03: Justification and Feasibility of Neural Stem Cell Sparing in Whole
Brain Irradiation Using VMAT.
AB - PURPOSE: To determine the impact of radiation on neural stem cells and examine
the feasibility of neural stem cell sparing using volumetric modulated arc
therapy (VMAT) for whole brain irradiation. METHODS: Murine neural stem cells
were harvested from the sub-ventricular zone (SVZ), cultured and assessed for
radio-sensitivity and differentiation potential in response to radiation (0-6Gy).
Clonogenic survival of these cells was compared to that of tumor cells derived
from the murine PTEN-/-/Kras+ spontaneous brain tumor model. The differentiation
potential of neural stem cells surviving irradiation was examined by allowing the
cells to differentiate for five days and analyzing cell types. In order to
address the feasibility of neural stem cell sparing, a typical 3D whole brain
treatment was compared to VMAT, in which the neural stem cell compartment,
designated and contoured as the lateral ventricles with a 3-5mm margin, was
spared. Whole brain dose coverage was maintained similarly to conventional 3D
treatment, while minimizing the dose to the stem cell compartment. RESULTS:
Neural stem cells are significantly more radio-sensitive than their tumor
counterparts (2Gy, p=0.018), and the neuronal differentiation capacity of stem
cells that survive radiation treatment is markedly diminished. Compared to
conventional 3D treatment, VMAT reduces radiation dose to the stem cell SVZ
compartment while maintaining adequate coverage of the whole brain. CONCLUSIONS:
Radiation-induced cognitive decline from whole brain irradiation is of particular
clinical relevance. Cognitive functions are strongly influenced by the activity
of neural stem cells, thus stem cell sparing may help mitigate radiation-induced
cognitive decline. To our knowledge, this is the first study to confirm that
radiation induces impaired neuronal differentiation at clinically relevant doses,
and that improved stem cell sparing of the lateral ventricles (SVZ) is feasible
using VMAT. Thus our studies confirm that VMAT should be examined further for
clinical relevance in whole brain irradiation.
PMID- 28519064
TI - SU-E-J-187: Evaluation of the Effects of Dose on 4DCT-Calculated Lung
Ventilation.
AB - PURPOSE: To investigate the effects of radiation therapy (RT) treatment dose on
ventilation. METHODS: Optical flow deformable image registration of the normal
end-expiration and end-inspiration phases of 4DCT images was used to correlate
the voxels between the two phases. 4DCT sets from before and after RT were used
to derive ventilation for 3 SBRT lung patients. Planning dose and normalized
ventilation were superimposed on the CT volume resulting in each voxel having a
volume, a normalized ventilation and a dose. From these values a 3D dose
ventilation-volume surfaces was created. The surface was integrated over dose to
reduce the 3D surface to a 2D histogram that is easier to interpret. RESULTS: For
lung tissue regions receiving more than 20 Gy, a decrease in ventilation was
observed in the three patients. Patient A (time between scans, T=26 months)
showed an increase in ventilation for regions receiving a dose smaller than 20
Gy, whereas patients B (T=3 months) and C (T=6 months) did not show any change
for these regions. Mean ventilation within the 20 Gy region for patient A was
0.57 before RT and 0.51 after RT; and 0.54 before and 0.48 after RT for the 30 Gy
region. Mean ventilation for the 20 Gy region for patient B was 0.49 before RT
and 0.47 after RT, for the 30 Gy region mean ventilation was 0.49 Gy before and
0.45 Gy after RT. Patient C's mean ventilation for the 20 Gy region was 0.54
before RT and 0.50 after RT, for the 30 Gy region mean ventilation was 0.54
before RT and 0.49 after RT. CONCLUSIONS: Ventilation before and after radiation
therapy can be measured using 4DCT and deformable image registration techniques.
In a preliminary application of this approach for three patients, changes in
ventilation were observed with a weak correlation between ventilation change and
dose. Partially supported by a grant from Varian Medical Systems.
PMID- 28519065
TI - SU-E-T-14: Modeling of 3D Positron Emission Activity Distributions Induced by
Proton Irradiation: A Semi-Empirical Method.
AB - PURPOSE: to present and validate a method for modeling three-dimensional positron
emission (PE) activity distributions induced by proton beam irradiation for
PET/CT delivery verification studies in homogeneous media. METHODS: the method
relies on modeling the 3D proton flux distribution by combining the analytical
expression for the depth reduction of proton flux with the empirically obtained
lateral distribution. The latter is extracted from the corresponding dose
distribution under the assumption that the projectile energy is nearly constant
in the lateral plane. The same assumption allows calculating the 3D induced
activity distributions from proton flux distributions by parameterizing the
energy-dependent activation cross-sections in terms of depth via the energy-range
relation. Results of this modeling approach were validated against experimental
PET/CT data from three phantom deliveries: unmodulated (pristine) beam, spread
out Bragg peak (SOBP) delivery without a range compensator, and SOBP with a range
compensator. BANG3-Pro2 polymer gel was used as a phantom material because of its
elemental soft-tissue equivalence. RESULTS: the agreement between modeled and
measured activity distributions was evaluated using 3D gamma index analysis
method, which, despite being traditionally reserved for dose distribution
comparisons, is sufficiently general to be applied to other quantities. The
evaluation criteria were dictated by limitations of PET imaging and were chosen
to correspond to count rate uncertainty (6% value difference) and spatial
resolution (4 mm distance to agreement). With these criteria and the threshold of
6%, the fraction of evaluated voxels passing the gamma evaluation was 97.9% for
the pristine beam, 98.9% for the SOBP without compensator, and 98.5% for SOBP
with compensator. CONCLUSIONS: results of gamma evaluation indicate that the
activity distributions produced by the model are consistent with experimental
data within the uncertainties of PET imaging for clinical proton beams
deliveries. This work was supported by the Bankhead-Coley Florida Biomedical
Research Program under Grant No. 1BD10-34212.
PMID- 28519066
TI - SU-E-J-198: Bioluminescence Monitoring of Metastatic Breast Cancer: Quantitative
Assessment of Radiation Treatment Effects and Tracking of Tumor Cells.
AB - PURPOSE: To evaluate radiation treatment effects on mammary carcinoma cells,
quantitative photon radiance were monitored to track light-emitting cancer cells
and metastasis using in vivo bioluminescence imaging. METHODS: Eight female
BALB/c mice aged 8 weeks were orthotopically injected with 5*104/cc 4T1 tumor
cells into the abdominal mammary gland. The firefly luciferase-based
bioluminescence images were acquired every 2-3 days for 1 month. Bioluminescent
intensity was analyzed in average surface radiance (photons/sec/cm2 /sr) taken in
3-dimensional bioluminescence tomography (BLT). After 1 week, single-radiation
dose of 20 Gy was delivered by orthovoltage X-rays. Variation of detected
bioluminescence signals emitted from molecular cancer cells was depicted on BLT
images. To delineate tumor volumes according to bioluminescence intensity on
anatomical images for radiation therapy, BLT images were registered with the
micro computed tomography (CT) images using surface-constrained warping. RESULTS:
Multispectral BLT images elaborated on early detection of cancer cells,
characteristics of tumor growth, and metastasis for more accurate determination
of internal bioluminescent sources. The radiation-treated mice having only
primary tumor volumes showed 67% decrease in bioluminescent signals, while the
mice with metastatic cancer cells suggested 88% reduction, as compared to the
control group. Registration of BLT with CT images guided molecular cancer cells
on anatomical coordinates. CONCLUSIONS: The BLT imaging was a useful tool to
localize cancer cells and to quantify radiation response. Application of BLT led
to more accurate definition of tumor volumes including molecular probe-based
microscopic cancer cells. Monitoring of bioluminescence signals enables to
diagnose real-time metastatic behavior of cancer cells and determine optimal
radiation treatment strategies adapted to tumor characteristics.
PMID- 28519067
TI - SU-E-T-24: Development and Implementation of an Automated Algorithm to Determine
Radiation Isocenter, Radiation vs. Light Field Coincidence, and Analyze Strip
Tests.
AB - PURPOSE: The aim of this study was to develop a phantom and analysis software
that could be used to quickly and accurately determine the location of radiation
isocenter using the Electronic Portal Imaging Device (EPID). The phantom could
then be used as a static reference point for performing other tests including:
radiation vs. light field coincidence, MLC and Jaw strip tests, and Varian
Optical Guidance Platform (OGP) calibration. METHODS: The solution proposed uses
a collimator setting of 10*10 cm to acquire EPID images of the new phantom
constructed from LEGO(r) blocks. Images from a number of gantry and collimator
angles are analyzed by the software to determine the position of the jaws and
center of the phantom in each image. The distance between a chosen jaw and the
phantom center is then compared to the same distance measured after a 180 degree
collimator rotation to determine if the phantom is centered in the dimension
being investigated. The accuracy of the algorithm's measurements were verified by
independent measurement to be approximately equal to the detector's pitch. Light
versus radiation field as well as MLC and Jaw strip tests are performed using
measurements based on the phantom center once located at the radiation isocenter.
RESULTS: Reproducibility tests show that the algorithm's results were objectively
repeatable. Additionally, the phantom and software are completely independent of
linac vendor and this study presents results from two major linac manufacturers.
An OGP calibration array was also integrated into the phantom to allow
calibration of the OGP while the phantom is positioned at radiation isocenter to
reduce setup uncertainty contained in the calibration. CONCLUSIONS: This solution
offers a quick, objective method to perform isocenter localization as well as
laser alignment, OGP calibration, and other tests on a monthly basis.
PMID- 28519068
TI - Long Noncoding RNA GAS5 Suppresses Cell Growth and Epithelial-Mesenchymal
Transition in Osteosarcoma by Regulating the miR-221/ARHI Pathway.
AB - Dysregulated long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) play key roles
in the development of human cancers. The lncRNA growth arrest-specific 5 (GAS5)
is reported to be a tumor suppressor in multiple cancers. However, the roles of
GAS5 and its related miRNAs in osteosarcoma are poorly understood. This study
explored the potential functions and mechanisms of GAS5 in the tumorigenesis of
osteosarcoma. Here, the expression of GAS5, miR-221 and aplasia Ras homologue
member I (ARHI) was determined in osteosarcoma tissues and cells by Real-time PCR
(RT-qPCR). The underlying mechanism of GAS5 in osteosarcoma growth was analyzed
via MTT, Transwell, RT-qPCR, Western blot, dual-luciferase reporter assay, RNA
immunoprecipitation, and xenograft models after GAS5 overexpression. GAS5 and
ARHI levels were significantly reduced, while miR-221 increased, both in
osteosarcoma tissues and cells. Overexpression of GAS5 suppressed the
proliferation, migration, and epithelial-mesenchymal transition (EMT) of
osteosarcoma cells. GAS5 could directly bind to miR-221 to decrease miR-221
expression and enhance ARHI expression. The effect of GAS5 overexpression on the
proliferation, migration and EMT was reversed by miR-221 mimics or ARHI siRNA in
osteosarcoma cells. Additionally, GAS5 suppressed tumor volume, Ki-67 and PCNA
staining, and EMT process in the development of osteosarcoma in vivo. Taken
together, lncRNA GAS5 functions as a competing endogenous RNA for miR-221 to
suppress cell growth and EMT in osteosarcoma by regulating the miR-221/ARHI
pathway. J. Cell. Biochem. 118: 4772-4781, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28519244
TI - Neonatal Abstinence Syndrome: Update on Diagnostic and Therapeutic Strategies.
AB - Substance use among pregnant women is a major public health issue. Both
prescription opioid use and illicit opioid abuse have increased dramatically in
recent years. Prolonged in utero drug exposure may result in neonatal abstinence
syndrome (NAS), an acute multisystemic clinical entity that occurs in the first
days of life. This syndrome is caused by abrupt discontinuation of fetal exposure
to licit or illicit drugs chronically consumed by the mother during pregnancy and
transmitted to the fetus through the placenta. It usually requires prolonged
hospitalization and may have long-term effects. The interplay of many factors
contributes to its clinical heterogeneity, and its pathophysiology has not been
fully unveiled. The first step in NAS management consists of nonpharmacologic
interventions and includes promoting breastfeeding when not contraindicated. If
withdrawal signs become severe, pharmacotherapy is needed. The Finnegan scoring
system supports care providers across the pharmacotherapy process from initiation
through the monitoring phase, until weaning and discontinuation. However, a
standardized approach to pharmacotherapy is still lacking. Morphine is usually
the first-line agent to treat NAS. Methadone is a valid option, but its safety
profile is not completely known. Phenobarbital, despite its lack of effect on
gastrointestinal symptoms and unfavorable pharmacologic features, has been
identified as a second-line agent to be used in infants unresponsive to opiates.
Although buprenorphine and clonidine seem promising, their use requires further
validation. Long-term developmental effects of NAS therapy call for more
comprehensive, longitudinal assessments. In this article, key points for use of
recommended therapies are outlined, and directions for future research are
suggested.
PMID- 28519481
TI - SU-E-I-35: Experience with Th Zero Gravity Suit.
AB - PURPOSE: To compare the effectiveness of the Zero Gravity Suit (CFI Medical
Solutions) in reducing the annual dose received by one physician in the Cardiac
Catheterization Lab. METHODS: A physician with a history of receiving high annual
dose equivalents was purchased a Zero Gravity Suit. Film badges (Landauer) were
worn at the collar and waist and monitored monthly. Previous dose history was
acquired via the Landauer Exposure Report Archive. Annual values for Deep Dose
Equivalent (DDE), Eye Dose Equivalent (LDE), and Shallow Dose Equivalent (SDE)
were compared for the first full year of the Zero Gravity Suit (2011) to the
previous four years (2007-2010). Readings for 2009 and 2007 were corrected for
improper wear of the film badges. RESULTS: The reduction in dose equivalent for
DDE ranged from 70%-87%. The reduction in dose equivalent for LDE ranged from 16%
60%. The reduction in dose equivalent for SDE ranged from 16%-60%. CONCLUSIONS:
It was determined that the Zero Gravity Suit is effective at reducing the
exposure of a physician with a history of high annual dose equivalents in our
facilities Cardiac Catheterization Lab. While the suit did reduce the LDE and SDE
it was more effective at reducing the DDE. During 2010 the suit was acquired
midyear. The dose equivalent values would likely be similar to 2011 if the suit
was introduced at the beginning of the year. In 2009 the physician was pregnant
and attempting a reduced workload. The physician only uses the suit if a
procedure is expected to take longer than fifteen minutes. The accuracy of the
study is dependent upon the physician wearing the badges consistently and
correctly and the physician using the Zero Gravity Suit consistently.
PMID- 28519482
TI - SU-E-I-07: Proposal for a Novel Algorithm of Effective Dose Evaluation for
Medical Radiation Exposure.
AB - PURPOSE: The validity of effective dose (ED) in medical applications, which
mostly involving partial-organ irradiation, has long been argued. We now propose
a new algorithm of effective dose evaluation for medical radiation exposure. The
new algorithm will include new Relative Volume Factors, or RVFs, to account for
the relative irradiated volume of the partially-irradiated organs, such as skin
and bone marrow. METHODS: To validate the proposed algorithm, three ED evaluation
methods were applied to five neuro-imaging protocols of a C-arm cone-beam CT: 1)
MOSFET-anthropomorphic- phantom measurement for organ doses, ED evaluated with
the original ICRP algorithm; 2) using the same MOSFET-measured organ doses, ED
evaluated with the new algorithm; and 3) Monte Carlo (PCXMC, developed by STUK)
dose estimation as gold standard. RESULTS: For all five imaging protocols, the ED
evaluations by the new algorithm agreed very well with the Monte Carlo simulation
results (within 10% difference), whereas the original ICRP algorithm
overestimated EDs by approximately a factor of 2. CONCLUSIONS: The proposed
algorithm provides a more accurate estimation of ED in medical exposures than the
original ICRP algorithm. It potentially establishes the ED as a more reasonable
index for cross-protocol dose comparison.
PMID- 28519483
TI - SU-E-I-56: Threshold Effect of ASIR Before Which Image Improve and After Which
Image Degrades.
AB - PURPOSE: This study showed to what extent ASIR improves CT-image and to what
extent it degrades it. METHODS: In our study we used GE HD750 CT-scanner, Siemens
Sensation CT-scanner, Catphan, PTW-pin-ion- chamber, CTDI-phantom. We measured
the CT-dose using the PTW-pinion-chamber and CTDI-phantom. Image-quality and
noise were evaluated using catphan and GE water phantom. RESULTS: Image noise
reduce as higher levels of ASIR are applied. A phantom scan showed that 50%ASIR
with 50% lower-dose (10.8mGy) achieved the same image noise of standard FBP image
with full dose 21.7mGy (noise~5). To confirm that the two same-noise images
retain same image-quality, two scans were compared; one with full dose
260mAs(21.7mGy) and the other one with 50% lower dose 130mAs(10.8mGy). The
results showed that ASIR failed to retain the same quality. For high contrast
resolution, 50%ASIR reduced the resolution of patterns = 71p/cm, however it
improved the detectability of patterns = 61p/cm. ASIR has degraded the CNR of the
low-contrast-objects of = 5HU (CNR of 1.4 at 260mAs STND to CNR of 1.08 at 130mAs
ASIR), however it improved the CNR of the low-contrast-objects of = 10HU (CNR of
2.35 at 260mAs STND to CNR of 2.63 at 130mAs ASIR). ASIR degraded the edges and
killed some of the small objects. This shows that ASIR has a critical point of
improve/degrade. Also, ASIR can improve images for the same dose, but with high
levels of ASIR (e.g. 100%ASIR), cause disapear of small low contrast objects
(e.g. 2mm). CONCLUSIONS: People think that ASIR only improves image and reduces
patient dose. Our study showed that ASIR has some drawbacks. There is a threshold
before wich ASIR is positive and after which ASIR is negative. Recently only GE
provide ASIR in the market but our study showed that other CTs such as Siemens
can do similar performance like ASIR.
PMID- 28519484
TI - SU-E-I-28: Development of Graphic Patient Models for a Real-Time Skin Dose
Tracking System (DTS) for Fluoroscopic Interventional Procedures.
AB - PURPOSE: To develop a library of graphic human models that closely match patients
undergoing interventional fluoroscopic procedures in order to obtain an accurate
estimate of their skin dose. METHODS: A dose tracking system (DTS) has been
developed that calculates the dose to the patient's skin in real time during
fluoroscopic procedures based on a graphical simulation of the x-ray system and
the patient. The calculation is performed using a lookup table containing values
of mGy per mAs at a reference point and inverse-square correction using the
distance from the source to individual points on the skin. For proper inverse
square correction, the external shape of the graphic should closely match that of
the patient. We are in the process of developing a library of 3D human graphic
models categorized as a function of basic body type, sex, height and weight. Two
different open- source software applications are being used to develop graphic
models with varying weights and heights, to 'morph' the shapes for body type and
to 'pose' them for proper positioning on the table. The DTS software is being
designed such that the most appropriate body graphic can be automatically
selected based on input of several basic patient dimensional metrics. RESULTS: A
series of male and female body graphic models have been developed which vary in
weight and height. Matching pairs have been constructed with arms at the side and
over the head to simulate the usual placement in cardiac procedures. The error in
skin dose calculation due to inverse-square correction is expected to be below 5%
if the graphic can match the position of the patient's skin surface within 1 cm.
CONCLUSIONS: A library of categorized body shapes should allow close matching of
the graphic to the patient shape allowing more accurate determination of skin
dose with the DTS. Support for this work was provided in part by NIH grants
R43FD0158401, R44FD0158402, R01EB002873 and R01EB008425, and by Toshiba Medical
Systems Corporation.
PMID- 28519485
TI - SU-E-E-05: An Educational Physical Environment Concept with Close Research and
Clinical Collaborations.
AB - PURPOSE: To create a physical environment where imaging medical physicists can be
educated in a real-work, clinical and research setting in close collaboration
with professionals such as physicians, biomedical engineers, and other medical
personnel. METHODS: A single building structure has been designed where medical
physics students can be immersed in a collaborative clinical and research
educational environment. RESULTS: A Clinical Translational Research Center has
been constructed on the top four floors over a new Global Vascular Institute
(GVI) which is connected to the main university hospital complex and adjacent to
radiation therapy facilities. The research and educational component including
offices, labs, and conference rooms for the Medical Physics Program is on the top
floor and dedicated research imaging suites (fluoroscopic interventional systems,
CT, PET/CT, and MRI) along with complete animal facilities and additional
research labs for cardiac and vascular investigators are on the two top floors.
An atrium and numerous meeting spaces are in place to encourage informal
communication among students and science and clinical investigators. The clinical
GVI, which occupies the lower four floors, has a full upper floor containing 15
vascular imaging suites for cardiac, neuro, and peripheral vascular imaging and
interventions while the floors below have short-term hotel-like patient and
family rooms favoring ambulatory patients having minimally invasive procedures.
Medical physics didactic education is designed to take place in modern meeting
rooms; however, because of the close proximity to research labs and clinical
suites, students are expected to get a unique perspective on how research is done
and how it is translated into clinical practice. CONCLUSIONS: A new physical
structure has been built which enables medical physics education to be an
integral part of a highly collaborative clinical translational research
environment. Research funds provided by NIH grants and equipment grants from
Toshiba Medical Systems Corp.
PMID- 28519486
TI - SU-E-I-39: Intensive Monitoring of System Performance and Protocols on CT
Systems.
AB - PURPOSE: The regulatory response to the recent CT overdoses is still in the
process of being implemented. The more action taken before the regulations take
effect reduces the exposure of the institution to medical and legal problems.
Therefore, eighteen months ago we implemented an intensive QC program to ensure
CT safety. The first component was to monitor the dose and SNR produced by a
single CT examination weekly to identify changes. The second was to monitor
changes in the protocols. METHODS: We measured the CTDI and SNR for the routine
head examination. We developed a script to identify and log changes in any of the
234 protocols. RESULTS: Surprisingly, there were many changes to the protocols:
on one unit 388 protocols were changed on 26 dates over the 18 month period. The
reasons included: protocol optimization, scanner service, software reloads,
mistakes, mistakenly loading the protocols from another section's scanner. The
standard deviation of the CTDI was 2% to 3%. The dominant source of variation was
probably positioning. The standard deviation of the SNR was 4% to 9%. The entire
procedure requires 30min to 50min to test five CT scanners each week.
CONCLUSIONS: The standard deviations of the CTDI values and of the SNR values are
sufficiently small to allow anomalies to be identified using these relatively
simple methods. Frequent protocol checking is an important component to any QC
program.
PMID- 28519487
TI - SU-E-I-11: A Novel High Resolution CT Imager for a Breast SPECT-CT System.
AB - PURPOSE: To evaluate the intrinsic characteristics of a new high resolution,
large area, small bezel, digital imager developed for a dedicated SPECT-CT system
for fully-3D mammotomographic imaging applications. METHODS: A new flat panel
digital imager was developed having 127MUm pixels (identical to those in the
Paxscan 2520) with an active 40*30cm area and 3200*2304 total pixels, which is
well suited for pendant breast imaging close to the chest wall. The readout and
driver ASIC TAB bonding pads were arranged on only two sides of the imager plate,
to eliminate dead edge spacing. A special housing was developed to accommodate
this imaging plate providing very narrow 8mm edges (bezels) on two orthogonal
sides The TFT array imager was coated with 600MUm thick micro-columnar CsI, which
provides >90% absorption in the breast CT (60-80kVp) x-ray energy range. It
provides better than 70% absorption for RQA5 (70kVp 21mm Al filter) x- ray
radiation. The readout ASICs are connected to 14 bit A/D converters, and special
readout ASICs with gain switching feature, which provide an additional 4bit
virtual (2-3 effective) dynamic range. RESULTS: The MTF is ~7.5% at the 3.9 lp/mm
Nyquist frequency. The NPS curves continuously decrease with increasing spatial
frequencies, characteristic of scintillator based imagers. The excellent DQE (0)
measured at RQA5 is ~75% in the 0.1-1mR dose range and ~10% at the Nyquist
frequency. The imager has excellent linearity over the full dynamic range, and
high contrast images are readily acquired. CONCLUSIONS: The new 4030 flat panel
imager is a high resolution, state of the art detector, ideal for breast imaging
and other applications. This detector is included in the SPECT-CT device in
development.
PMID- 28519488
TI - SU-E-I-49: Influence of Scanner Output Measurement Technique on KERMA Ratios in
CT.
AB - PURPOSE: KERMA ratios (RK) are defined as the ratio of KERMA measured at a
specific phantom location (K) to in-air isocenter CT scanner output (KCT). In
this work we investigate the impact of measurement methodology on KCT values.
METHODS: OSL dosimeter chips were used to measure KCT for a GE VCT scanner (GE
Medical Systems, Waukesha WI), using the 40 mm nominal beam width. Methods
included a single point measurement at the center of the beam (1 tube rotation),
and extended z-axis measurements using multiple adjacent OSL's (7.5 cm extent),
with single tube rotation, multiple contiguous axial scans, and helical scans
(pitch of 1.375). Measurements were made in air and on the scan table at 80 and
120 kV. RESULTS: Averaged single point measurements were consistent, with a mean
coefficient of variation of 2.5%. For extended measurements with a single tube
rotation, the mean value was equivalent to the single point measurements. For
multiple contiguous axial scans, the in-air KCT values were higher than the
single rotation mean value and single point measurements by 13% and 10.3% at 120
and 80 kV, respectively, and for the on-table measurements the values were 14.9%
and 8.1% higher at 120 and 80 kV, respectively. The increase is due to beam
overlap caused by z- axis over-beaming. Extended measurements using helical
scanning were equivalent to the multiple rotation axial measurements when
corrected for the helical pitch. For all methodologies, the in-air values
exceeded the on- table measurements by an average of 23% and 19.4% at 80 and 120
kV, respectively. CONCLUSIONS: Scanner KCT values must be measured to allow organ
dose estimation using published RK values. It is imperative that the KCT
measurement methodology is the same as for the published values, or large errors
may be introduced into the resulting organ dose estimates.
PMID- 28519489
TI - SU-E-I-21: Effect of Different Fluorescent Lights with Various Colors of a
Reading Room on Chromaticity of LCD.
AB - PURPOSE: To examine variation of chromaticity of LCD in different types of
fluorescent lights in a reading room. METHODS: A color LCD (RX320, antiglare
type, 450 cd/m2 , three-megapixel, Eizo Nanao), and a monochrome LCD (G31-S, anti
glare type, 450 cd/m2 , three-megapixel, Eizo Nanao) were used in this study. The
chromaticity in grayscale images with eighteen luminance levels were measured
under five types of fluorescent lights with different color spectrums (Daylight:
6,700 K, Natural white: 5,000 K, White: 4,200 K, Warm white: 3,500 K, Light bulb:
3,000 K) by using a colorimeter (CS-200: KONICA MINOLTA). The chromaticity of
LCDs was measured at various ambient lighting conditions (a dark room, 36, and
300 lux) and different types of fluorescent lights. RESULTS: The chromaticity of
LCDs measured under ambient lights was changed from that measured in a dark room.
The chromaticity of LCDs varied with different types of fluorescent lights. As
illuminance of the room increased, variations in chromaticity at relatively lower
luminance levels increased. The direction of changes in chromaticity shifted to
the color for each fluorescent light. CONCLUSIONS: Fluorescent lights having
different color spectra affect the chromaticity of LCDs.
PMID- 28519490
TI - SU-E-I-32: Sterile Radiation Reduction Gloves May Be Contraindicated in
Fluoroscopically Guided Interventions.
AB - PURPOSE: Sterile radiation reduction gloves have been widely used in the past
decade to provide modest decreases in operator hand dose when the hands are
placed in the field of view (FOV). While multiple publications have quantified
the potential dose reduction from the use of such gloves, possible effects on the
patient have not yet been assessed. The aim of this study was to determine if
radiation reduction gloves can Result in a significant increase in patient dose
and increased risk of radiation induced skin injury when used in interventional
radiology. METHODS: The effect of radiation reduction gloves when used in the FOV
was determined by measurement of patient entrance exposure rate (EER) for a
variety of patient sizes and varying operating and magnification modes. EERs were
measured with no glove in the FOV, with one glove and, to replicate the actions
of many dose-conscious radiologists, with double gloves in the FOV. RESULTS:
Compared to an ungloved hand, the use of a single radiation reduction glove near
the center of the FOV results in a 2-fold average increase in patient EER. The
use of double radiation reduction gloves results in a 3-fold average increase in
EER. In both cases, this increase was only weakly dependent on the size of the
patient and on the operating and magnification modes used. In fact, patient
thicknesses ranging from 6-14 inches and operating modes ranging from low-dose
fluoroscopy to DSA produced less than a 20% deviation from the increases in EER
quoted above. CONCLUSIONS: When used in the FOV, radiation reduction gloves can
substantially increase patient EER. This increase in patient dose, when compared
with the relatively small published reduction in extremity dose provided to the
operator, may make their use contraindicated in cases where radiation induced
skin injury is a possible risk.
PMID- 28519491
TI - SU-E-I-04: Implementation of a Fast Monte Carlo Scatter Correction for Cone- Beam
Computed Tomography.
AB - PURPOSE: To improve image quality in cone-beam computed tomography (CBCT) scans
by implementation of a fast and accurate MC-based scatter correction algorithm.
METHODS: A Solid WaterTM phantom was imaged on a Varian OBI CBCT scanner using
the standard-dose head protocol (100 kVp, 151 mAs, partial-angle). A fast Monte
Carlo simulation developed in the EGSnrc framework was used to transport photons
through the uncorrected CBCT scan. From the simulation output, the contribution
from both primary and scattered photons for each projection image was estimated.
Using these estimates, a subtractive scatter correction was performed on the CBCT
projection data. This correction procedure was repeated iteratively, using the
previous scatter corrected scan as input to the Monte Carlo simulation. RESULTS:
Implementation of the scatter correction algorithm on real CBCT data was shown to
help mitigate scatter-induced artifacts, such as cupping and streaking. The
scatter corrected images were also shown to have improved accuracy in
reconstructed attenuation coefficient values. In a region of interest centered on
the Solid Water phantom, the number of voxels agreeing to within 10% of the
theoretical attenuation coefficient increased from 46% to 97% after two
iterations of the scatter correction. CONCLUSIONS: These results suggest that the
proposed scatter correction algorithm is successful in improving image quality in
real CBCT images. The accuracy of the attenuation coefficients extracted from the
corrected CBCT scan renders the data suitable for on-the-fly dose recalculations,
as well as vastly improved image registration.
PMID- 28519492
TI - SU-E-I-43: Reducing Scanogram Dose Without Affecting the Planned Tube Current
Modulation of a Diagnostic Abdomen/pelvis CT Scan.
AB - PURPOSE: In tube current modulated CT scans, scanograms (localizer radiographs)
are needed prior to the diagnostic scan to obtain the attenuation properties of
each patient which is then used to plan the mA modulation of the diagnostic scan.
The purpose of this study was to investigate whether lowering the dual-scanogram
dose affects the mA modulation scheme. Although scanograms use relatively low
dose, the goal of this study is to reduce radiation dose from scanograms even
further in keeping with the ALARA principle. METHODS: Abdomen-pelvis CT exams
were performed on an anthropomorphic phantom (Pixy RS102 phantom, Radiology
Support Devices) using a Toshiba Aquilion CT scanner with SUREExposure tube
current modulation. Various combinations of kVp and mAs were used to acquire dual
scanograms (AP and lateral); parameters for the diagnostic scan following the
scanograms were fixed. For each kVp, the mA was reduced in intervals from a
baseline 100% mA level, including 80%, 60%, 40%, 20% of the baseline, and a
minimum level of 10mA. For each exam the resulting CTDIvol and total mAs were
compared. RESULTS: When scanogram kVp was reduced from 120kVp (default) to 100kVp
and 80kVp, both CTDIvol and total mAs of the diagnostic scan increased slightly
(up to 4.3%). When scanogram mA was decreased in intervals representing 80%, 60%,
40%, and 20% of baseline, there was little to no effect (less than 3%) on CTDIvol
and total mAs for the diagnostic scan. For the minimum mA scanograms, CTDIvol was
affected by up to 5.5% and total mAs was affected by up to 6.1% (at 80kVp). It
should be noted that for 120kVp, the decrease of both CTDIvol and total mAs was
within 1% at all reduced scanogram dose levels. CONCLUSIONS: It was suggested to
use the default 120kVp scanogram to minimize the dose from the diagnostic scan.
However, the mA of dual-scanograms may be significantly reduced without affecting
planned mA of the exam.
PMID- 28519493
TI - SU-E-I-15: Comparison of State-Of-The-Art Interpolation-Based Metal Artifact
Reduction (MAR) Algorithms for Cone-Beam Computed Tomography (CBCT).
AB - PURPOSE: To compare four metal-artifact-reduction (MAR) algorithms in their
ability to correct the typical streaking artifacts that appear in cone- beam
computed tomography (CBCT) images. METHODS: The goal was to compare the strengths
and weaknesses of four MAR algorithms, Basic; Wei; Mazin and Meyer, using typical
clinical situations where metal is present. Three clinical situations were
evaluated: fiducial markers in the abdomen; hip implants and multiple dental
fillings. The algorithms take original CBCT projections as input and produce a
corrected image. The location of the metal is identified in the CBCT images and a
forward projection identifies which pixels in the projections need to be replaced
by interpolation of neighboring pixels. The three advanced algorithms extend the
Basic technique with more sophisticated interpolation schemes. Wei and Meyer
identify the high contrast structures using image segmentation in order to reduce
their appearance in the projections before interpolation. Mazin corrects the
original projections using a forward projection of the Basic correction. RESULTS:
All the algorithms reduced the streak artifacts typical of metal structures.
Nevertheless, depending upon the clinical task, the algorithms also added shading
and streaks which reduced the overall visual impression. Images containing
fiducial markers in the abdomen showed obvious improvements; images containing
hip implants were improved but also showed distracting shading artifacts; and,
images with multiple dental fillings all appeared visually worse than the
uncorrected images. In almost all cases, Mazin outperformed the other approaches
and introduced the fewest additional streaks and shading artifacts. CONCLUSIONS:
This work indicates that the Mazin algorithm is best suited for clinical usage of
MAR. Furthermore the algorithm is fairly simple and can be computational very
efficient making it well suited for clinical use. Nevertheless, the overall
improvement is highly dependent on the individual characteristics of the original
image. For dental implants no correction is recommended.
PMID- 28519494
TI - SU-E-I-53: Optimal KVp for Image Quality and Noise in Iodine Contrast in Head
CTA.
AB - PURPOSE: For brain CT perfusion it is well established that 80 kVp is optimal.
Although neuro-CT angiography is somewhat similar, emphasis is on the detection
of aneurysms and related vascular pathologies throughout the brain. Thus it is
necessary to visualize small and large blood vessels with contrast material, as
well as form multi-planar views and 3D images, so image quality and noise in
addition to contrast are important for thin slices. A study was initiated to
determine the optimal kVp for neuro-CTA. METHODS: A customized version of a
commercial head phantom (CIRS 007TE-27 medium adult head CT dose phantom) was
purchased to facilitate quantitative measurements with iodinated contrast
material, contrast for white and gray matter, and to maintain the ability to
perform dosimetry. The customization consisted of adding four 25 mm holes, 35 mm
from the center arranged at 45 degree angles from the center, with solid rods
equivalent with brain, white, and gray matter, as well as four fillable vials
were included for study of contrast agents. Dosimetry measurements were carried
out with standard pencil chamber and with 0.6 cc ionization chamber. For study of
the optimal kVp for a head CTA, the vials were filled with four different
concentrations of contrast, approximating low to medium concentrations that would
be expected in such a study. The standard CTA protocol was followed, 64 * 0.625,
pitch 0.53, rotation speed 0.5 second, and CTDIvol was kept constant for each
kVp. RESULTS: The best contrast was observed at 80 kVp; however, in order to
achieve noise in CTA low enough to be clinically useful there may be issues with
tube current capability for a clinical technique. Clinical investigation is
underway. CONCLUSIONS: The best balance of contrast and noise currently possible
will be achieved at 100 kVp in a clinical scan.
PMID- 28519495
TI - SU-E-I-06: Measurement of Skin Dose from Dental Cone-Beam CT Scans.
AB - PURPOSE: To directly measure skin dose using point-dosimeters from dental cone
beam CT (CBCT) scans. To compare the results among three different dental CBCT
scanners and compare the CBCT results with those from a conventional panoramic
and cephalomic dental imaging system. METHODS: A head anthropomorphic phantom was
used with nanoDOT dosimeters attached to specified anatomic landmarks of selected
radiosensitive tissues of interest. To ensure reliable measurement results, three
dosimeters were used for each location. The phantom was scanned under various
modes of operation and scan protocols for typical dental exams on three dental
CBCT systems plus a conventional dental imaging system. The Landauer OSL nanoDOT
dosimeters were calibrated under the same imaging condition as the head phantom
scan protocols, and specifically for each of the imaging systems. Using nanoDOT
dosimeters, skin doses at several positions on the surface of an adult head
anthropomorphic phantom were measured for clinical dental imaging. RESULTS: The
measured skin doses ranged from 0.04 to 4.62mGy depending on dosimeter positions
and imaging systems. The highest dose location was at the parotid surface for all
three CBCT scanners. The surface doses to the locations of the eyes were ~4.0mGy,
well below the 500mGy threshold for possibly causing cataract development. The
results depend on x-ray tube output (kVp and mAs) and also are sensitive to SFOV.
Comparing to the conventional dental imaging system operated in panoramic and
cephalometric modes, doses from all three CBCT systems were at least an order of
magnitude higher. No image artifact was caused by presence of nanoDOT dosimeters
in the head phantom images. CONCLUSIONS: Direct measurements of skin dose using
nanoDOT dosimeters provided accurate skin dose values without any image
artifacts. The results of skin dose measurements serve as dose references in
guiding future dose optimization efforts in dental CBCT imaging.
PMID- 28519496
TI - SU-E-I-45: Measurement of CT Dose to An HDPE Phantom Using Calorimetry: A
Feasibility Study.
AB - PURPOSE: Radiation dose in CT is traditionally evaluated using an ionization
chamber calibrated in terms of air kerma in a phantom of specific dimensions. The
radiation absorbed dose, J/kg, can also be realized directly by measuring the
temperature rise in the medium. We investigate using this primary method to
determine the CT dose at a point (a few mm), using the recently proposed (APMM
TG220) high density polyethylene (HDPE) phantom as a medium. METHODS: The
calorimeter detection scheme is adapted from the second generation NIST water
calorimeter using sensitive thermistors in a Wheatstone bridge powered by a lock
in amplifier. The temperature sensitivity is about 3 microK. The expected
temperature rise in PE is about 0.6 mK per Gy. The thermistor sensors were placed
inside a 26 cm dia. * 10 cm HDPE phantom. Two preliminary tests were made: at a
linear accelerator with a 6 MV photon beam, and at a 16-slice CT scanner with a
120 kV beam, each with the thermal sensor and with a calibrated ionization
chamber. RESULTS: The 6 MV photon beam with 10 on/off cycles at 60 s each yielded
the (uncorrected) run-to-run average dose of 3.06 Gy per cycle (sdm 0.3%), about
8% higher than the Result from the ionization chamber (calibrated in terms of
absorbed to water). The CT measurements were also made in the middle section of
the TG200 30 cm phantom. Twenty consecutive axial scans at 250 mA, which delivers
a nominal accumulated dose (CTDIvol) of 705 mGy in 50 s at three axial and three
radial locations were measured. The accumulated dose measured by the ionization
chamber at the center of the smaller phantom was 347 mGy. CONCLUSIONS: The
calorimeter data show qualitative tracking of the chamber measurements. Detailed
thermal and electrical analysis of the system are planned to obtain quantitative
results.
PMID- 28519497
TI - SU-E-I-17: Characterization of Rotating Source MicroCT for Evaluating in Vivo
Murine Trabecular Bone.
AB - PURPOSE: The objective of this study is to determine the optimal physical
parameters of the Inveon Multi-modality microCT to assess the trabecular bone of
mice. METHODS: The x-ray Source-to-Axis Distance is increased from 100mm to 183mm
to 263mm. Similarly, combining local pixels, or binning, is examined from no
binning to 2 to 4. Energy is varied from 40kVp to 80kVp in 10kVp increments and
filter thickness is changed from no filtration to 1.5mmAl in 0.5mmAl increments.
A lucite phantom with six different density-equivalent rods is used to measure
changes in Hounsfield Units (HU) and calibrate Bone Mineral Density estimation.
Mice are scanned at four different magnification and binning combinations to
evaluate dose and microstructure changes of high to low resolution images.
RESULTS: An increase in magnification and decrease in binning results in an
effective pixel size ranging from 95MUm to 9MUm. This decreases the signal to
noise ratio from 19.2 to 1.7HU and density estimation from 1585 to 1383mg/cc for
1250mg/cc equivalent material. Increasing the average energy of the radiation
beam also decreases HU estimation from 1466HU to 1132HU. Higher resolution scans
extend the scan time and absorbed dose from 5.1 to 13.4min and 3.9 to 125cGy
respectively. An 18 micron pixel provides distinguishable trabecular bone surface
from cortices with a 4.2HU signal to noise ratio. CONCLUSIONS: A high
magnification, binning of 2, 80kVp beam with a 0.5mmAl filter are the optimal
parameters to evaluate the trabecular bone of mice for the Inveon MM microCT
unit. This work was supported by the National Institute of Health grants
(1R01CA154491- 01, 1R03AR055333-01A1 and 1K12-HD055887-01). This work was also
supported by PHS Cancer Center Support Grant P30 CA77398. This work was also
supported by PHS Cancer Center Support Grant P30 CA77398. Susanta K Hui is a
scholar of the BIRCWH (Building Interdisciplinary Careers in Women's Health)
program. Luke Arentsen is supported by the Grant in Aid funding from the
Universit.
PMID- 28519498
TI - SU-E-I-55: Cumulative Radiation Exposure and Cancer Risk Estimates in Pediatric
Hydrocephalus Patients Undergoing Repeat Or Multiple CT.
AB - PURPOSE: Children with a shunt for hydrocephalus often undergo multiple follow-up
head CT scans, increasing the risk for long-term effects of ionizing radiation.
The study is to define a conservative estimate of frequent CT head scans for
pediatric patients with a shunt for hydrocephalus and to quantify their
cumulative CT radiation doses and lifetime attributable risk of developing
cancer. METHODS: All children at age of less than 17 years with a shunt for
hydrocephalus who underwent non-enhanced head CT at a tertiary hospital between
2007 and 2011 were identified and categorized by total number of scans per study
period as non-frequently (<3), or frequently (>=3) scanned. We retrospectively
identified the number of CT head scans, dose length product (DLP) and the applied
scan parameters according to age, gender and study time. Effective doses were
estimated using age- specific DLP to effective dose conversion coefficients.
Lifetime attributable cancer risk was then estimated based on the BEIR VII.
RESULTS: During the 5-year study period, a total of 264 children (mean age, 5.5
years; range less than one month to 17 years; 146 boys and 118 girls) underwent
747 CT head scans, of whom 100 patients (41.7%) were frequently scanned. The
median and mean of frequently scans are 4 and 5.33, with the most frequently
scanned patient underwent 34 CT head scans from birth to 4 years and 1 month age.
The average effective dose was 15.71 mSv, ranging from 3.65 mSv to 64.70 mSv. The
estimated lifetime attributable cancer risk is one in 637, ranging from one in
2739 to one in 155, based on the standardized BEIR VII conversion of 0.0001/mSv.
CONCLUSIONS: The children with shunts have a substantially increased risk of
developing cancer from cumulative CT radiation exposure.
PMID- 28519499
TI - SU-E-I-27: Effect of Focal Spot Choice on the System Performance of a High-
Resolution Micro-Angiographic Fluoroscope (MAF) Detector.
AB - PURPOSE: The generalized metrics of GMTF and GDQE were used to evaluate the
effect of focal-spot choice on system performance of the Micro- Angiographic
Fluoroscope (MAF) imager with a geometric magnification common for neuro
endovascular interventions. METHODS: The MAF, a newly developed high-resolution
detector with very low instrumentation noise and large variable gain, was used
for the study. It has 35-micron pixels and a 500-micron thick CsI HR-type
phosphor. The detector MTF was measured using the slanted edge method and the
focal spot MTF's were measured using a standard pin-hole assembly. For the
comparison analysis, the GMTF and GDQE were determined for three different focal
spots (0.3 mm, 0.5 mm and, 0.8 mm) with a magnification factor of 1.25. A
stainless- steel stent was also imaged with the same magnification for all three
focal spots. RESULTS: The MAF's performance is affected significantly by the
choice of focal-spot size because of its very high resolution. The GMTF and GDQE
comparison for three focal spots showed significant degradation, increasing from
small to large focal spot. The GMTF values were found to be 0.09, 0.05 and 0.01
at 5 cycles/mm for the small, medium and large focal spot, respectively. The
corresponding values for GDQE were 0.1, 0.03 and 0.001. These results
demonstrating the effect of choice of focal spot on the image quality are
supported by line profiles obtained across the stent images. CONCLUSIONS: The
results of this study demonstrate the significance of focal-spot size on system
performance when using a high-resolution detector with a realistic magnification
and shows the importance of choosing the minimum focal-spot size. (Support: NIH
Grant R01EB002873) NIH Grants R01-EB008425, R01-EB002873 and an equipment grant
from Toshiba Medical Systems Corp.
PMID- 28519500
TI - SU-E-I-38: Optimizing CT Slice Width Measurements.
AB - PURPOSE: For almost four decades bead and wire ramps have been used in the
evaluation of slice width as part of QA testing for CT scanners. While each of
these approaches have been recognized and accepted as reliable, in this paper we
investigate the differences, advantages and limitations of these tools. Moreover,
we study the effect of varying the field of view (FOV) and focal spot size.
METHODS: The Catphan(r) 700 phantom includes two pairs of bead ramps (coarse and
fine) and a pair of wire ramps in the same module providing an ideal setting for
comparing bead ramps and wire ramps. The phantom was scanned using three devices
from two different manufacturers. The data set consisted of 428 slices of
0.5,1,2,4,8 and 10 mm thickness. For the study of FOV and focal spot, 512 slices
from the Catphan(r) 600 were acquired. All images were analyzed using Image Owl
Catphan(r) QA software. RESULTS: For 0.5mm slices, bead ramps gave more accurate
and precise (lower variance) estimation of the thickness than wire ramps. For 2-4
mm slices, the two approaches performed on equal terms while for the thickest
slices (8 and 10mm), the wires gave more precise results. For thin slices, a
small FOV (100mm) gave better results and lower spread than a large FOV (240mm).
Finally, a small focal spot gave significantly better results than a large one
using wire ramps for 0.5 and 1mm slices. CONCLUSIONS: For measuring thin slices,
the use of bead ramps, with adequately small FOV and a small focal spot should be
advised. For measuring thick slices, wire ramps will give less variability
although bead ramps give equally accurate results on average. Funding provided by
The Phantom Laboratory, Incorporated and Image Owl, Incorporated.
PMID- 28519501
TI - SU-E-I-10: Putting Teeth into Your CT Dosimetry Program: Approaches to Cone- Beam
Dental/Maxillofacial CT Dosimetry.
AB - PURPOSE: To review and compare different approaches to the problem of dosimetry
for limited field-of-view (FOV) cone beam CT devices for dental and maxillofacial
applications. METHODS: The determination of patient doses from specialized, cone
beam CT devices for dental and maxillofacial work requires medical physicists to
re-evaluate their dosimetry methods. These devices work in cone-beam geometry,
with an axial field dimension on the order of the lengths of the standard head
CTDI phantom and pencil ionization chamber. They may also utilize less than 360
degree scans, resulting in asymmetrical radiation distributions. This operating
regime is far from that for which conventional CT dosimetry was designed, and
alternative approaches must be considered. The alternatives include extensions of
conventional CT dosimetry currently used for large axial FOV scanners (e.g. the
extended CTDI parameter (CTDIe) for the Toshiba Aquillion One with 160 mm axial
FOV) and the new method based on point dosimetry measurements recently formalized
in AAPM Report TG-111. Conventional, modified-conventional, and TG-111 dosimetry
measurements are used in two CT dose phantoms (adult head and pediatric head) to
obtain dose indices for the Planmeca ProMax 3D Max dental CT scanner. Surface
dose maps are generated using radiochromic film for correlation with the chamber
dosimetry. RESULTS: Results for the three dosimetry approaches are compared for
the specific case of the ProMax 3D Max scanner. Strengths and weaknesses of the
three measurement paradigms for this type of application are compared.
CONCLUSIONS: The increasing availability of specialized scanners operating in
full cone-beam mode will require the clinical medical physicist to be conversant
with extensions to the CT dose index methodology suitable for this equipment.
PMID- 28519502
TI - SU-E-I-48: Comparison of CTDIw and Averaged CTDI Over X-Y Plane.
AB - PURPOSE: The goal of this study is to investigate the accuracy of using CTDIw to
estimate the averaged CTDI over x-y plane. METHODS: We used a Siemens Sensation
16 slice scanner, a nested 3 piece CTDI phantom with diameters of 10, 16, and 32
cm for each piece, a CT pencil ion chamber, and aluminum oxide OSL dosimeters. In
axial mode, we measured the exposure with ion chamber at the 3, 6, 9, and 12
o'clock positions at distances of 4, 7, and 15 cm from the center of a 32 cm CTDI
phantom, as well as at the center of the phantom. Measurements were performed at
80, 100, 120, and 140 kVp on the adult abdomen, adult head, and pediatric body
phantom, using only the distances of 0, 4, and 7 cm from the phantom center for
the smaller 16 cm diameter phantom. We did similar measurements using nanoDot
dosimeters and the 32 cm phantom at 120 kVp in helical mode using a pitch of 0.8,
1.0, and 1.2. RESULTS: The data obtained at four different outer clock positions
was averaged and three models (linear, quadratic, and exponential) were used to
fit exposure as a function of distance to the phantom center. We calculated the
average CTDI over the x- y plane mathematically using the above models and
compared the results with traditional CTDIw. In axial mode, the difference is
within 6% for 32 cm phantom, with a slight increase in variance at low kVp, while
the difference is within 1% for the 16 cm phantom. In helical mode with OSLs, the
difference is within 2.5% for pitch 0.8-1.2. CONCLUSIONS: The current CTDIw
provides an accurate estimate of the averaged CTDI over the x-y plane for both
axial and helical modes.
PMID- 28519503
TI - SU-E-I-20: The Application of Traditional Snake Model and Balloon-Snake Model in
Automatic Organ Contouring.
AB - PURPOSE: To compare the traditional Snake model and Balloon-Snake model on
automatic organ contouring. METHODS: For tumors in brain, chest and abdomen, two
patients were enrolled for each part. Grey matter, lung and liver for each
patient were contoured automatically by Snake model and Balloon-Snake model, and
were also contoured manually by radiologist respectively. Characteristics and
dynamic capabilities were compared between the two models. RESULTS: The
traditional Snake model will bring good contouring Result only if the primary
contour is close enough to the target edge. But, if the force field area is
relatively small, the automatic contouring will not bring good Result on boundary
deep concave. The Balloon-Snake model can overcome those shortcomings and improve
the traditional Snake model. However, the primary model of Balloon-Snake can not
cross border, doesn't work well on boundary cracks reconstruction, has small
force field. CONCLUSIONS: The Balloon-Snake model improved the traditional Snake
model and has better dynamic capabilities. It has also more practical value on
automatic organ contouring.
PMID- 28519504
TI - SU-E-I-31: Evaluating Brain Imaging Material (BIM) as a Brain Tissue Surrogate
for Use in Neuro-Endovascular Imaged Guided Intervention (EIGI) Research.
AB - PURPOSE: A brain tissue surrogate material was needed to fill the anatomical
cavity of a skull to create a phantom for use in simulated Neuro-EIGI procedures.
To enable diagnostic and interventional procedure simulation, the BIM must fit
into and be congruous with the interior surface of the skull, be reusable, and
allow the implantation of vascular phantoms. The material must reasonably
reproduce the automatic technique parameter selections observed during Neuro-EIGI
procedures. METHODS: We formulated a putty- like material to be used as the BIM.
Its x-ray attenuation properties were evaluated by comparison of the fluoroscopic
and radiographic technique parameters automatically selected for a BIM-filled
skull on a Toshiba Infinix angiographic C-arm unit to those of a solid
anthropomorphic head phantom at various projection angles. The same comparison
was made between the skull phantom without BIM in the cavity and the
anthropomorphic head phantom. The BIM linear attenuation coefficient was
calculated and compared to that of PMMA, a common tissue analog plastic. RESULTS:
The BIM keeps its shape, is moldable and reusable, and is congruent to the
skull's interior surfaces. It allows for insertion and interchange of various
custom vascular phantoms at proper anatomic locations. Addition of the BIM to the
skull cavity improves the matching of the automatically selected parameters to
those of the anthropomorphic phantom by an average of 96.3% for mAs and by 4.2%
for kVp in fluoroscopy mode and by 88.6% and 9.0%, respectively, in DSA mode. The
BIM's experimental and theoretical linear attenuation coefficient for the RQA5
spectrum differed from PMMA's by about 30%. CONCLUSIONS: Despite the difference
in attenuation coefficients between the PMMA and BIM, the BIM is a good surrogate
material for Neuro-EIGI research as shown by its properties of congruity,
reusability, and device implantation, along with the demonstrated improvement of
automatically selected technique parameters. Supported in part by: NIH Grants R01
EB008425, R01-EB002873, and an equipment grant from Toshiba Medical Systems Corp.
PMID- 28519505
TI - SU-E-I-03: Scatter and Beam Hardening Correction for MUCBCT Scanners Using Monte
Carlo.
AB - PURPOSE: Micro CBCT scanners have a broad spectrum of applications in medicine
and material science. However, CBCT suffers from scatter radiation and spectral
effects such as beam hardening (BH). In this work an iterative BH- and scatter
correction algorithm was developed using Monte Carlo (MC) methods. METHODS: Two
MUCBCT scanner models (XtremeCT and MUCT100 from SCANCO Medical AG) were
simulated using EGSnrc/EGS++. The scanner measures the attenuation of X-rays
passing through the phantom and interacting in a scintillating detector. The MC
method is used to characterize the influence of the scattering and BH- effects.
In addition, an analytical model is developed in order to correct for the
scattering effect. For this purpose, by using MC methods, different scatter
components were analyzed with respect to the number of scatter interactions
within the given geometry. For the BH-effect, after assessing the detector
response for an equivalent mono-energetic and scatter-free system using MC
methods, an analytical correction model was developed. Both correction methods
were implemented as an iterative reconstruction correction algorithm and were
tested for various phantoms. RESULTS: MC simulations show that the amounts of
correction for the scattering and BH- effects are in the same order of magnitude.
The correction term for scattering effects is a function of the scatter to
primary ratio only and is mainly due to single scattered particles. The
contribution of multiple scattered particles to the total scatter signal is small
and can be approximated by a constant. In all cases tested, the reconstructed
linear attenuation coefficients converge to the mono-energetic reference values
after 2-3 iteration steps with a deviation of about 1%. CONCLUSIONS: By using an
iterative correction algorithm using single scatter approximation, BH- and
scatter correction can be performed accurately for MUCBCT scanners. This work was
supported by CTI-10629.1 and SCANCO Medical AG.
PMID- 28519506
TI - SU-E-I-42: Measurement of X-Ray Beam Width and Geometric Efficiency in MDCT Using
Radiochromic Films.
AB - PURPOSE: The purpose of this work was to measure the x-ray beam width and
geometric efficiency (GE) of a multi detector computed tomography scanner (MDCT)
for different beam collimations using radiochromic films. In MDCT, the primary
beam width extends the nominal beam collimation to irradiate the active detector
elements uniformly (called 'over-beaming') which contributes to increased
radiation dose to the patient compared to single detector CT. Therefore, the
precise determination of the primary beam width and GE is of value for any CT
dose calculation using Monte Carlo or analytical methods. METHODS: Single axial
dose profiles free in air were measured for 6 different beam collimations nT for
a Siemens SOMATOM Sensation 64 Scanner with Gafchromic XR-QA2 films. The films
were calibrated relative to the measured charge of a PTW semiflex ionization
chamber (type: 31010) for a single rotation in the CT scanner at the largest
available beam collimation of 28.8 mm. The beam energy for all measurements in
this work was set to 120 kVp. For every measured dose profile and beam
collimation the GEin-air and the full-width-at-half- maximum value (FWHM) as a
value for the x-ray beam width was determined. Over-beaming factors FWHM / nT
were calculated accordingly. RESULTS: For MDCT beam collimations from 7.2 (12*0.6
mm) to 28.8 (24*1.2 mm) the geometric efficiency was between 58 and 85 %. The
over- beaming factor ranged from 1.43 to 1.11. For beam collimations of 1*5 mm
and 1*10 mm the GE was 77 % and 84 % respectively. The over-beaming factors were
close to 1, as expected. CONCLUSIONS: This work has shown that radiochromic films
can be used for accurate x-ray beam width and geometric efficiency measurements
due to their high spatial resolution. The measured free-in-air geometric
efficiency and the over-beaming factor depend strongly on beam collimation.
PMID- 28519507
TI - SU-E-I-14: Evaluation of Image Quality Parameters of Small and Full Field of View
Cone Beam Computed Tomography Dental Imaging Systems.
AB - PURPOSE: CBCT systems are being used in dental preoperative planning, which rely
on 3D surface model representations of the jaw, using a segmentation algorithm
for extracting the bony tissues. However, CBCT systems have differences of
imaging parameters, which affect the image quality and segmentation process,
influencing the accuracy of the 3D surface models used in preoperative implant
planning. The purpose of this study was to evaluate image quality parameters of
different types of CBCT systems, showing their potentialities and limitations for
preoperative planning. METHODS: Images were acquired using the systems: i-CAT
(Imaging Sciences International Inc., USA); ProMax 3Ds (Planmeca Oy, Finland);
Kodak 9500 Cone Beam 3D and Kodak 9000C Cone Beam 3D (Kodak Dental Systems, USA).
CBCT systems were divided into categories, related to their field of view size:
Small Field of View (SFOV) and Full Field of View (FFOV) systems. Image quality
parameters evaluated were: CT number accuracy, uniformity, noise level, and
artifacts. Measurements were performed in slices around the center of the
phantom. RESULTS: CT numbers are highly affected by the amount of mass outside
the reconstructed volume, confirming the relation between density variability and
imaging volume. The mean CT number shows little correspondence to that of the
traditional CT protocols. The variability is especially high in the case for SFOV
systems. Uniformity artifacts occur at the top or bottom of the FOV, and Result
in voxel values that are unsuitable for CT number accuracy analysis. SFOV systems
showed a higher noise level (11,9%) comparing to FFOV systems (4.4%). CONCLUSION:
The experiments showed that the size and position of the FOV affect the image
quality for all CBCT systems. The study was limited to the CBCT systems that were
accessible when this study was conducted. Whether new CBCT systems models would
perform differently remains to be investigated.
PMID- 28519508
TI - SU-E-I-52: Noise Level and Contrast Dependent Behavior of MTF in Iterative
Reconstruction CT Imaging.
AB - PURPOSE: Iterative reconstruction (IR) technique is growingly used in clinical CT
imaging due to its ability to provide improved image quality at lower patient
doses. However, the nonlinear frequency response of IR technique, which may
affect quantitative analysis, is rarely explored. This study evaluates noise
level and contrast dependent behavior of MTF in IR CT imaging with a multi
contrast slit phantom scanned at different dose levels. METHODS: A multi-contrast
slit phantom was created consisting of acrylic panel and aluminum foils of
different thickness. Images were acquired on multi-detector CT (Discovery CT750
HD: GE) at two dose levels (10mAs and 200mAs), and were reconstructed using FBP
and two IR technique (ASIR50 and VEO). Line spread functions were extracted
across slits of two different thickness (80um and 144um) on images scanned at two
dose levels, and were Fourier transformed to evaluate the MTFs of IR and FBP
reconstruction techniques, producing a total of 12 MTF curves. RESULTS: MTF of
200mAs scan showed clearly higher responses up to 28% than that of 100mAs scan in
VEO, marginally higher values up to 5% in ASIR50, and were in good agreement in
FBP. At same dose level, the MTFs with higher contrast slit (144um) showed
marginally higher response than that of lower contrast slit (80um) in VEO and
ASIR50. CONCLUSIONS: Our study revealed that MTF of IR technique degrades
depending on noise level at low dose scan. Therefore, we recommend that its
characteristic should be considered in quantitative analysis such as lesion size
measurement.
PMID- 28519509
TI - SU-E-I-24: Determining the Optimal B-Values to Use in Diffusion Weighted Imaging
for Differentiating Benign and Malignant Breast Lesions.
AB - PURPOSE: To investigate and determine the optimal b-values for Diffusion Weighted
Imaging(DWI) for Apparent Diffusion Coefficient(ADC) maps in differentiating
normal, benign and malignant breast tissue. METHODS: Twenty-five patients
underwent diffusion-weighted magnetic resonance imaging (DWI-MRI) and
conventional breast MRI with suspicious breast fmdings(BIRADS >4). Breast lesions
were defined by pathology. The DWI was acquired with different b-values ranging
from 0,500, 600,750 and 1000s/mm2 . Apparent Diffusion Coefficient(ADC) maps of
breast tissue were constructed using different b-values, e.g., using either 2 b
values(0- 1000) or combinations of 3 or more (0,500,1000 or 0,600,750,1000).
Quantitative analyses of the ADC maps of glandular, fatty and lesion tissue were
obtained. Ratios of lesion to glandular tissue(L/GT) and signal to noise(SNR)
were assessed. Paired t-tests were performed for statistical significance.
RESULTS: Eighteen patients had invasive ductal carcinoma and 7 had benign breast
lesions. The mean ADC value for malignant lesions using all b values was 1.17+/
0.16*10-3mm2 /s with a lesion to glandular(L/GT) ratio=0.65. The benign lesions,
ADC map value was 1.86+/-0.03*10-3mm2 /s with L/GT=0.98. There was a significant
difference(P<0.05) between benign and malignant lesions ADC map value.The lowest
SNR(12+/-6) was with single b-values. There was a significant difference(P<0.05)
in SNR with multiple b-values(34+/-6) compared to single b-values. The highest
SNR was given by using two b values greater than 500. Finally, the background
noise for all combinations was surprising stable and ranged between 60+/-20%.
CONCLUSIONS: This is the first study to investigate the effect of changing
different b values in DWI breast imaging. There were significant differences in
the SNR between single and multiple b values. Our data show suggest that the
recommended b-values for DWI in breast are 0, and two that are 500 or greater.
Therefore use of at least 3 b-values in DWI/ADC mapping of breast lesions are
needed for better characterization of benign and malignant breast tissue.
P50CA88843, Avon Foundation for Women:01-2008-012, U01CA070095, andU01CA140204.
PMID- 28519510
TI - SU-E-I-16: Automated Liver Segmentation Method for CBCT Dataset by Probabilistic
Atlas Construction.
AB - PURPOSE: The aiming is getting accurate liver contour structures automatically
for following adaptive radiation therapy in daily CBCT images which is very low
contrast comparing the planning CT. METHODS: Probabilistic atlas is constructed
by 50 intravenous contrast planning CT images by iterative affine registration
process. The incoming CBCT images are registered with the atlas using deformable
registration algorithm which is based on edge preserving scale space, and the
liver contour structures are generated automatically by using the deformation
map. Incorporating the intensity distribution of candidate liver region into the
segmentation processing, we can further remove the irrelative tissue from the
original liver region. Our algorithm is capable of segmenting the liver from low
contrast cone beam CT images. In our probabilistic atlas construction process,
firstly one training data is arbitrarily chosen as reference image while the rest
of training datasets are registered to this reference using the affine
transformation. For improving the efficiency of our method, iterative
construction method is employed. The resulting atlas which is gained before is
used as the reference image for the following atlas construction. This process
can be iterated by many loops. However, we used two iterations for efficiency.
This iterative atlas construction process can avoid bias toward the specific
patient. RESULTS: The experiments are tested on 10 newly incoming patient data.
The volumetric overlap is on an average 87%-94% comparing with manually segmented
tumors by oncologists. After evaluation by clinical oncologists, they concluded
that the segmentation results are close to the manual results and the liver
contours on CBCT which is produced by the deformation field automatically can be
used for following adaptive radiation therapy. CONCLUSIONS: We can conclude that
the proposed segmentation method is very effective with low contrast CBCT for
adaptive radiation therapy in daily using.
PMID- 28519511
TI - SU-E-I-54: Evaluation of High Contrast Resolution for Model Based Iterative
Reconstruction of Sinus Examinations.
AB - PURPOSE: To evaluate high contrast resolution of Model Based Iterative
Reconstruction used with typical sinus examination acquisition parameters.
METHODS: MBIR has recently become available as a recon option on a clinical
scanner (Discovery HD750, GE Healthcare). In this work, we evaluate high contrast
resolution for scan and reconstruction options that are available for sinus
examinations. For this study we used our adult sinus CT protocol reconstructed
with filtered back projection, and two alternative scans reconstructed with IR.
Our conventional adult sinus CT protocol utilizes a high resolution scan mode
which is not compatible with the scanner's IR recon option. The two additional
scans are with high resolution option off, one with the head SFOV, and one with
the body SFOV. Using IR and the head SFOV, reconstructed images have a 1024 *
1024 pixel matrix. Using IR and the body SFOV, reconstructed images have a 512 *
512 pixel matrix. Three evaluations of high contrast resolution are made for
these images. A wire phantom is scanned for assessment of image modulation
transfer function. The bar patterns of the ACR phantom are visually assessed for
quality in both axial and coronal reformats. RESULTS: MTF curves show 50% values
of 6.8, 7.5, and 7.7 lp/cm for Body IR 512 * 512, Head IR 1024 * 1024, and
filtered back projection with HD Bone kernel. The 10% MFT curves for these
reconstructions are 11.2, 11.9, and 12.1 lp/cm. Visual evaluation of the ACR
phantom at 15 cm display field of view demonstrates resolution of the 10 lp/cm
bar patterns for all reconstructions with better visualization of the axial
versus coronal recons. CONCLUSIONS: MBIR reconstruction demonstrates high
contrast resolution that is comparable with our conventional sinus examination.
PMID- 28519512
TI - SU-E-I-26: Estimation of Micro-Angiographic Fluoroscope (MAF) Gain Settings for
Digital Subtraction Angiography (DSA) Based on the Fluoroscopic Exposure.
AB - PURPOSE: The MAF is a new high-resolution detector which is being clinically
evaluated in neuro-vascular procedures. The detector contains a large-dynamic
range, high-sensitivity light image intensifier with variable gain. Since the MAF
is a research prototype only partially integrated with the clinical system, x-ray
technique parameters must be set manually. To improve workflow we developed an
automatic method to estimate and set the proper LII voltage (MAF gain) for DSA
acquisition based on the fluoroscopic parameters. METHODS: The detector entrance
exposure (XD) can be written as the x-ray tube output exposure (Xo) times an
object attenuation factor and an inverse-square correction. If the object
attenuation, scatter and distances are unchanged and the effect of x-ray kVp
changes are neglected, then the DSA XD can be expressed as the ratio of
Xo(DSA)/Xo(Fluoroscopy) multiplied with XD(fluoroscopy). We measured Xo for
fluoroscopy and DSA for mAs and kVp ranges appropriate to neuro- vascular
interventions and fit the data with a 2D function. To estimate the
XD(Fluoroscopy) we derived a curve of XD versus LII-voltage for a mid- dynamic
range average pixel gray-level. Since the MAF system during clinical fluoroscopy
automatically adjusts the LII voltage until the desired gray-level value is
achieved, by reading that voltage we can estimate the XD(Fluoroscopy). Using the
2D-fit function, Xo(DSA) is automatically calculated for the kVp and mA values
set and XD(DSA) can be estimated using the relation above. Using the inverse LII
calibration curve, the proper LII-voltage can be determined for the desired
average gray-level. RESULTS: The algorithm was implemented and evaluated in
thirty-two in-vivo DSA runs on rabbits. The proper LII voltage was selected in
all cases with no failures. CONCLUSIONS: Using the fluoroscopic LII gain setting
to determine the appropriate DSA setting can greatly improve the workflow in
clinical evaluations of the MAF. NIH Grants R01-EB008425, R01-EB002873 and an
equipment grant from Toshiba Medical Systems Corp.
PMID- 28519514
TI - SU-E-I-09: Patient Organ Doses from KV-CBCT Acquisitions as Function of Patient
Size and Scan Protocols.
AB - PURPOSE: To investigate the organ dose dependence on patient size and position
resulting from an image guidance procedures. Depending upon the degree of
variability between patients, the feasibility tabulating the organ dose based
upon patient size and imaging acquisition procedure. Such tables could be useful
in estimating and accounting for organ dose resulting from imaging procedures.
METHODS: Monte-Carlo methods were used to calculate radiation dose to the patient
resulting from a kV CBCT imaging scan based upon CT image data. A Python program
was created to generate DVHs using the calculated 3D dose matrix and the DICOM-RT
Structure Set for the patient. A number of head and pelvic CT scans were used in
the study, and the resulting DVHs were analyzed to determine the variation of
organ dose as a function of patient size. RESULTS: For the head scans in supine
position, the average of the mean doses for some organs, along with the standard
deviation in those mean doses, are as follows:Brainstem: 0.25cGy +/-
0.02cGyBrain: 0.26cGy +/- 0.01cGyOptic Chiasm: 0.22 +/- 0.03cGyBone: 0.55 +/-
0.04cGyAnterior Skin: 0.13 +/- 0.05cGyPosterior Skin: 0.23 +/- 0.06cGyEye:
0.11cGy +/- 0.05cGyFor Pelvic scans, dose to organs such as rectum, have likewise
been shown to have some variation between patients of different sizes.
CONCLUSIONS: The results show that it is possible to express organ dose as a
function of imaging procedure, imaging device, scan location, body size, and
orientation. For example, using a standard head scan on an OBI 1.4 system, the
dose to the eye ranged from 0.05-0.20cGy, depending upon the patient size.
Considering the amount of imaging dose compared to the therapeutic dose, this
study indicates that organ dose could be estimated by using tabulated values
based upon the scan procedure and patient size.
PMID- 28519513
TI - SU-E-I-37: A Renewed Look at CT Numbers as Encountered in the Diagnostic and
Therapeutic Range.
AB - PURPOSE: With the development of RT treatment planning systems that use the
relationship between CT number and Electron Density (ED), rather than the Linear
Attenuation Coefficient (LAC) of a given material, a number of authors have
pointed out the divergence between the linearity of CT numbers vs. LAC in the
diagnostic range compared to the relationship between the CT number and ED. This
paper will review the differences and similarities, and describe a new set of
phantom test objects and automated software that can be used to automatically
assess both scales. In particular the relative importance of atomic number (Z)
and the relative impact of Coherent vs. Incoherent effects at high Z levels will
be evaluated. METHODS: A newly developed phantom (Catphan(r) 700) has an expanded
set of sensitometric samples of known density, electron density, and chemical
composition (Z effective). CT scans of the phantom were obtained at various
energies (kVp) and the measured CT numbers were compared to the known physical
characteristics mentioned above. Regressions between measured CT numbers, linear
attenuation coefficients (with and without coherent scattering effects), and
electron density for the materials were performed. Effects of different materials
and the inclusion of coherent scattering on linearity scale and effective energy
were established. RESULTS: The linearity scale and effective energy are shown to
be dependent on the selection of materials scanned and the inclusion/exclusion of
coherent scattering effects in the linear attenuation coefficients. Electron
density deviates significantly from a linear relationship with CT number.
CONCLUSIONS: Caveats accompanying high Z materials are reinforced regarding
application to the RT relationship between CT number and electron density.
Interesting results were obtained for the influence of coherent vs. incoherent
scattering, which appears to be important as the number of slices and scanning
volume increases in CT. Funding provided by The Phantom Laboratory, Incorporated
and Image Owl, Incorporated.
PMID- 28519515
TI - SU-E-I-47: Comparison of Risks for Two Medical Imaging Procedures.
AB - PURPOSE: Radiologists may need to decide which type of image procedure is most
appropriate for a particular patient. One factor relevant in making this decision
is the relative risk of secondary cancers due to each relevant procedure.
Differences in the risk posed by each method are not just due to the total
radiation dose imparted by each procedure, but also the distribution of absorbed
dose across various organs in the imaging procedure. Two imaging procedures with
the same total radiation dose may pose different risks of differential
sensitivity to radiation across organs. METHODS: New methods of radiation
dosimetry enable us to estimate the dose distribution across organs in individual
patients. We propose a measure of the relative risk of two medical imaging
procedures derived from the hazard function of cancer incidence. The relative
risk measure is shown to approximately equal to a weighted sum of the dose
difference in each organ. The weights are proportional to organ specific
incidence rates. The measure is also sensitive to factors such as the patient's
age at exposure to radiation, the attained age and gender, as well as the
incidence characteristics of the population to which the patient belongs. We
propose to quantify the effects of these factors using information from
publically available SEER database for US based patients as well as the LSS study
of atomic bomb survivors. The method is illustrated by application to a study
comparing chest and abdominal CT scans for a group of pediatric patients.
RESULTS: Fig. 1 shows higher absolute relative risk for those exposed at younger
ages, with chest scans being riskier for females while abdominal scans were
riskier for males. At higher ages, the relative risk is approximately equal.
CONCLUSIONS: Relative risks can quantify risks comparisons between imaging
procedures.
PMID- 28519516
TI - SU-E-I-19: Local Search Clustering Algorithm for DCE-MRI Analysis.
AB - PURPOSE: To develop a local search clustering algorithm for analyzing the dynamic
contrasted enhanced (DCE)-MRI data for determining the vascular permeability. The
clustered signal will have better contrast-to-noise ratio (CNR) and thus can
improve the analysis. METHODS: In DCE-MRI, data often suffer from low CNR. The
CNR is particularly poor in central nervous system and could lead to spurious
results. We propose a local search clustering algorithm that groups proximal
voxels with similar uptake curves and T1 values. The algorithm starts with a seed
voxel, and then grows outward to recruit new voxels into a cluster. Once a
cluster is formed, all members of the current cluster form a 'seed collection'
and the seed point of the cluster becomes the seed collection. The expansions and
updates continue with the seed point/collection until the stopping criterion is
met. To investigate the effectiveness of our clustering algorithm, we used a
64*64 2D Shepp-Logan phantom. Variations on the T1 values and permeability
parameters were applied on different regions in the phantom. The time resolution
was set to 30sec and 82 post-contrast data were created. After the DCE-MRI data
were generated, Gaussian noise was applied to the images to investigate the
effect of noise on the clustering algorithm. DCE analysis was performed on the
clustered data and the results were compared against the Result obtained from
voxel-by-voxel analysis. RESULTS: The addition of noise degraded the results of
DCE estimation. The clustering algorithm on average reduced the errors of the
permeability parameters by more than 50% compared to the voxel-by-voxel analysis.
CONCLUSIONS: We developed a local search clustering algorithm to segment the
concentration time curves of the DCE-MRI data. The proposed clustering algorithm
enhances the apparent CNR within the clustered data and reduces the errors of the
permeability parameters.
PMID- 28519517
TI - SU-E-I-58: Objective Models of Breast Shape Undergoing Mammography and
Tomosynthesis Using Principal Component Analysis.
AB - PURPOSE: To develop an objective model of the shape of the compressed breast
undergoing mammographic or tomosynthesis acquisition. METHODS: Automated
thresholding and edge detection was performed on 984 anonymized digital
mammograms (492 craniocaudal (CC) view mammograms and 492 medial lateral oblique
(MLO) view mammograms), to extract the edge of each breast. Principal Component
Analysis (PCA) was performed on these edge vectors to identify a limited set of
parameters and eigenvectors that. These parameters and eigenvectors comprise a
model that can be used to describe the breast shapes present in acquired
mammograms and to generate realistic models of breasts undergoing acquisition.
Sample breast shapes were then generated from this model and evaluated. The
mammograms in the database were previously acquired for a separate study and
authorized for use in further research. RESULTS: The PCA successfully identified
two principal components and their corresponding eigenvectors, forming the basis
for the breast shape model. The simulated breast shapes generated from the model
are reasonable approximations of clinically acquired mammograms. CONCLUSIONS:
Using PCA, we have obtained models of the compressed breast undergoing
mammographic or tomosynthesis acquisition based on objective analysis of a large
image database. Up to now, the breast in the CC view has been approximated as a
semi-circular tube, while there has been no objectively-obtained model for the
MLO view breast shape. Such models can be used for various breast imaging
research applications, such as x-ray scatter estimation and correction, dosimetry
estimates, and computer-aided detection and diagnosis.
PMID- 28519518
TI - SU-E-I-30: Impact of Physician Practice on Patient Radiation Dose during CT
Guided Biopsy Procedures.
AB - PURPOSE: The major concern with CT fluoroscopy is patient radiation dose, which
is determined by applied technical parameters as well as practitioner/operator
practice, e.g. habits and choice of dose saving features. This study is to
investigate the effects of these intangible factors on patient doses. METHODS:
381 patients underwent CT biopsy were retrospectively studied. Patient doses
(dose length product, DLP) were analyzed and compared. Comparisons were made
among physicians using only conventional intermittent shots, physicians using a
low mA dose saving feature, and physicians using a combination of both. Linear
regression analyses were performed to investigate any possible relationship
between the variables and the patient dose. The Patient detriment index (PDI) was
developed to set a threshold for the purpose of the Joint Commission sentinel
dose events monitoring. An odds ratio was calculated to determine the odds of a
group of patients receiving a dose above the median threshold when compared to
another group. RESULTS: The median DLP for all physicians was 1194 mGy-cm. There
is a significant difference (p<0.01) between the doses patients received
(DLP=539.8 +/-76 mGy-cm) when physicians used dose saving feature vs. when the
feature was not used (DLP=1269.7+/-659 mGy-cm). In general, those physicians who
used dose saving feature have a lower relative PDI (<1) compared to the PDIs (>1)
without dose feature. This is not absolute since some physicians who did not use
the dose saving feature have PDIs500cc)
were mounted on the torso phantoms and CT scanned for volume measurements.
RESULTS: For geometric phantoms, the OSI measured volume had accuracy (+/-1s) of
0.0%+/-1.6% (vs. geometric volume calculation) and 0.6%+/-3.8% (vs. water
containment experiment). For deformable torso phantoms, the volume change was
measured using OSI with an accuracy of 1.5%+/-2.5% against the measured volume
using CT imaging. Linear regression showed a one-to-one relationship between the
OSI volumes and CT volumes with a slope of 1.003 (r2=0.999). CONCLUSIONS: The
optical surface imaging system can accurately measure the volume of geometric
phantoms and the volume change of deformable torso phantoms. The accuracy is
about 3% against standard volume measurement methods. Further study on human
subjects is under investigation. Memorial Sloan-Kettering Cancer Center has a
reserach agreement with Vision RT, Inc.
PMID- 28519780
TI - SU-E-J-106: Atlas-Based Segmentation: Evaluation of a Multi-Atlas Approach for
Lung Cancer.
AB - PURPOSE: Previous studies have shown atlas-based segmentation using a single best
matched (SBM) atlas subject can significantly reduce contouring time. A new multi
atlas approach has been shown to provide greater accuracy than SBM for cancer of
the head and neck. The goal of this study was to evaluate the multi-atlas
technique for lung cancer treatment planning. METHODS: An institution's SBRT lung
atlas containing 82 subjects was utilized for atlas segmentation. Each atlas
subject contained manually defined contours of the esophagus, cord, heart, left
lung, right lung, and trachea. CT scans and contours for 16 subjects were
evaluated. SBM used the one automatically determined best match for segmentation.
Multi-atlas used multiple automatically determined best matches: 3, 4, and 5,
respectively. The final segmentation for multi-atlas was generated using Majority
Vote which comprises the area of overlap for at least half of the individual
segmentations (2 of 3, 2 of 4, and 3 of 5, respectively). Average Dice Similarity
Coefficients (DSC) were calculated for each structure to compare against manually
defined 'gold' standard contours for that subject. Overall percent improvement
was calculated as the proportion of the error corrected by the method, or %
difference on 1-DSC. RESULTS: All multi-atlas methods were significantly more
accurate than SBM (p-value < 0.0005) with average DSC of 0.802 +/- 0.172, 0.809
+/ 0.163, 0.802 +/- 0.182 respectively for Multi-3, Multi-4, and Multi-5 compared
to 0.773 +/- 0.187 for SBM. No significant differences existed between the
different multi-atlas approaches. Overall, Multi-4 showed the greatest
improvement over SBM with 16% improvement followed by Multi-3 and Multi-5 at 12%.
CONCLUSIONS: Each multi-atlas approach resulted in significantly more accurate
contours compared to the SBM. While still requiring some editing, this method for
segmentation using multiple atlases shows promise for further decreasing the
contouring time required for lung cancer. MIM Software Inc.
PMID- 28519781
TI - SU-E-J-78: Enhance Patient Positioning Accuracy with Optically Guided Frameless
Target Localization Technique for Intracranial Radiation Therapy.
AB - PURPOSE: To make use of the optical guided frameless stereotactic target
localization technique to detect the interfraction and intrafraction patient
positioning errors and correct the patient position for fractional intracranial
therapy, therefore, to enhance the patient positioning accuracy. METHODS: Four
patients who underwent fractionated intracranial intensity modulated radiation
therapy (IMRT) were studied. For each patient, in addition to the thermoplastic
head mask, frameless array and bite-block were used for patient positioning.
Optical guided frameless planning was utilized to define the coordinates of the
isocenter during the treatment planning procedure. In each treatment fraction,
the patient was first set up by matching the room lasers to the BB markers
attached on the mask. The optical guided frameless system then captured the
patient position and reported displacements of the current patient position to
the planned patient position. These displacements were called interfraction
errors. The treatment plan was designed to have up to 8 non-coplanar fields. Dose
delivery of the non-coplanar fields required couch rotation which introduced
isocenter displacements called intrafraction errors. Population statistics of
interfraction and intrafraction errors (4 patient, 110 fractions) were
calculated. The optical guided frameless system monitored the patient positioning
errors and provided guidance for correction prior to the dose delivery. RESULTS:
Among all patients and radiation treatment fractions, the overall detected
interfraction error was 3.6+/-1.3 mm (mean +/-SD) and the intrafraction error was
1.4+/-0.8 mm. Both types of errors were online corrected with the guidance of
optical guided frameless system. CONCLUSIONS: Conventional laser guided
thermoplastic mask patient position for intracranial therapy has interfraction
and intrafraction errors. The optical guided frameless target localization
technique allows clinicians to dectect and correct these errors online,
therefore, to enhance the patient positioning accuracy for intracranial radiation
therapy.
PMID- 28519782
TI - SU-E-J-117: Computer-Assisted Verification of Accumulated Dose Distribution
during the Treatment Time Based on Estimation of Four-Dimensional Dose
Distribution Using an Electronic Portal Imaging Device.
AB - PURPOSE: The accumulated dose distributions during the course of radiation
treatment are substantially important for verifying whether treatment dose
distributions are produced according to planned dose distributions. The purpose
of this study was to develop a computer-assisted verification method of
accumulated dose distribution during the irradiation of a tumor based on
estimation of four-dimensional (4D) dose distribution using an electronic portal
imaging device (EPID). METHODS: The 4D 'treatment' computed tomography (CT)
images during the irradiation were estimated based on affine transformations
including respiratory motions, which were derived by registration between a
planning portal dose image and treatment portal dose dynamic image. Planning
portal dose images were calculated from planning CT images and an algorithm for
calculation of dose spatial distribution. Treatment portal dose images were
estimated from EPID dynamic images obtained during a treatment time. The planning
portal dose images were registered to the treatment portal dose images to obtain
the affine transformation, which could include respiratory motion in a patient
body. The CT images at a treatment time were determined by deforming the planning
CT images using the affine transformation matrix. 4D dose distributions during a
treatment delivery were obtained by applying a dose calculation algorithm to the
4D treatment CT images. Finally, accumulated dose distributions during the course
of radiation treatment were verified with planned dose distributions. RESULTS: We
applied the proposed method to EPID dynamic images of 2 lung cancer patients, and
evaluated the difference in accumulated dose distribution between the plan and
treatment using a gamma evaluation (3mm/3%). The average pass rate for 2 cases
was 78.2%. CONCLUSIONS: The proposed method can be used for adaptively modifying
the plan based on the dose discrepancy between the plan and treatment. This work
was partially supported by Grant-in-Aid for Scientific Research (C) (22611011)
and Okawa Foundation for Information and Telecommunications.
PMID- 28519783
TI - SU-E-J-99: Automated Registration Method Based on Multi-Scale Edge Preserving
Scale Space for PET-CT Scanner.
AB - PURPOSE: The aiming is to improve the mutual information based registration
method for PET-CT scanner, which faces the challenges of high computational
complexity and high likelihood of being trapped into local optima due to an
absence of spatial information. METHODS: In this work, new multi-scale
registration framework called EPMR was proposed based upon an edge preserving
total variation L1 norm (TV-L1) scale space representation. TV-L1 scale space is
constructed by selecting edges and contours of images according to their size
rather than the intensity values of the image features. This ensures more
meaningful spatial information with EPMR framework for MI based registration.
Furthermore, we design an optimal estimation of the TV-L1 parameter in EPMR
framework by training and minimizing the transformation offset between the
registered pairs for automated registration in medical system. We validated our
EPMR method on multi-modal medical datasets from clinical studies with a combined
PET/CT scanner. We compared our registration framework with other traditional
registration approaches. RESULTS: Our experimental results demonstrated that our
method outperformed other methods in terms of the accuracy and robustness for
medical images. EPMR can always achieve small offset value, which is more close
to the ground truth, and the speed can be increased by 10%-14% comparing with
other method for PET-CT registration under the same condition. Furthermore,
clinical application by adaptive GTV (gross tumor volume) re-contouring for
clinical PET/CT image guided radiation therapy throughout the course of
radiotherapy is also studied, and the overlap between the automatically generated
contours for CT image and the contours delineated by the oncologist using for
theplanning system are on an average 90%. CONCLUSIONS: In this work, we presented
a novel scale space decomposition methodology to improve the traditional scale
space decomposition and performance of Mutual information based image
registration for PET-CT scanner.
PMID- 28519784
TI - SU-E-J-71: Dosimetric Impact of Setup Tolerance for Breast Radiation Therapy with
3D Surface Imaging.
AB - PURPOSE: 3D surface image guidance (3D SIG) has been shown to improve patient
positioning accuracy in the treatment of breast cancer, but limited information
is available regarding the dosimetric consequences of setup tolerances associated
with breast radiation therapy techniques. The purpose of this study was to
determine the magnitude of dose-delivery errors associated with setup tolerances
of 3 mm/3deg and 5 mm/5deg for set-up and monitoring of whole breast radiation
treatment using (3D SIG). METHODS: Five test patients were selected for direct
simulation of the maximum acceptable deviation from reference position for
tangential beams using field-in-field (FinF) techniques. Dosimetric impact was
determined by simulating the maximum allowable patient translations and
rotations, recalculating the dose distribution, and propagating the dosimetric
error for a full treatment course. For the planned and off-set positions,
dosimetric consequences were evaluated by examining the plan maximum dose, the
percent coverage of the prescription dose for the lumpectomy bed, the V20Gy and
V13Gy percentages for the ipsilateral lung, and the maximum point dose to the
heart. The results are shown in Table I below. RESULTS: For both 3 mm/3deg and 5
mm/5deg off-sets in relatively large-breasted patients (> 500 cc) no significant
change is observed. The ipsilateral lung V20Gy and V13Gy had a maximum increase
of 5.4% and 5.7%, respectively. Maximum dose to the heart increased by a maximum
of about 8% for those patients being treated to the left breast. The patient with
the largest dosimetric impact was relatively small-breasted with a lumpectomy
cavity in close proximity to the field borders. CONCLUSIONS: As tumor bed
coverage and ipsilateral lung dose were heavily impacted for the studied
tolerances, it may be beneficial to utilize an appropriately tighter tolerance in
patients with breast volume < 500 cc with tumor bed volumes near the periphery of
the field apertures.
PMID- 28519785
TI - SU-E-J-110: A Novel Level Set Active Contour Algorithm for Multimodality Joint
Segmentation/Registration Using the Jensen-Renyi Divergence.
AB - PURPOSE: To present a novel joint segmentation/registration for multimodality
image-guided and adaptive radiotherapy. A major challenge to this framework is
the sensitivity of many segmentation or registration algorithms to noise.
Presented is a level set active contour based on the Jensen-Renyi (JR) divergence
to achieve improved noise robustness in a multi-modality imaging space. METHODS:
To present a novel joint segmentation/registration for multimodality image-guided
and adaptive radiotherapy. A major challenge to this framework is the sensitivity
of many segmentation or registration algorithms to noise. Presented is a level
set active contour based on the Jensen-Renyi (JR) divergence to achieve improved
noise robustness in a multi-modality imaging space. RESULTS: It was found that JR
divergence when used for segmentation has an improved robustness to noise
compared to using mutual information, or other entropy-based metrics. The MI
metric failed at around 2/3 the noise power than the JR divergence. CONCLUSIONS:
The JR divergence metric is useful for the task of joint
segmentation/registration of multimodality images and shows improved results
compared entropy based metric. The algorithm can be easily modified to
incorporate non-intensity based images, which would allow applications into multi
modality and texture analysis.
PMID- 28519786
TI - SU-E-J-82: Improvement in Reproducibility of Lung Expansion Measures with
Respiratory Effort Correction.
AB - PURPOSE: Longitudinal measurements of pulmonary function must account for subject
variation when assessing radiation-induced changes. Previously, we reported intra
subject reproducibility of Jacobian-based measures of lung tissue expansion using
repeat 4DCT scans prior to radiation therapy without correcting for differences
in respiratory effort. In this study, we present two normalization schemes that
correct ventilation images for variations in respiratory effort. METHODS: Two
repeat 4DCT image acquisitions were collected before treatment from seven
patients. Using a tissue volume preserving deformable image registration
algorithm, two Jacobian ventilation maps were computed from separate
acquisitions. Two effort normalization strategies were investigated using
intermediated inspiration phases upon the principles of equivalent tidal volume
(ETV) and equivalent lung volume (ELV). Additional experiments were performed to
verify the effectiveness of the ETV method. Scatter plots of two ventilation maps
and statistical parameters of Jacobian ratio were compared before and after each
effort correction approach. RESULTS: The scatter plots of the ventilation maps
show improvement in measurement reproducibility using either the ETV or ELV
effort correction for all but one case. The one case that did not show
improvement had a very similar lung volumes and tidal volumes in the two studies,
so effort correction was unnecessary. The coefficient of variation (CV) of
Jacobian ratio improved by 21+/-11 percent (mean+/-standard deviation) after ETV,
and improved by 20+/-17 percent after ELV. Our experimental results on ETV show
the decrease of tidal volume difference in two acquisitions improves
reproducibility of lung expansion measures. CONCLUSIONS: ETV and ELV correction
methods improve the reproducibility of pulmonary function measurements in
subjects that have differences in respiratory effort in the baseline and followup
scans. Additional work is needed to investigate whether ETV or ELV is more
effective, and to develop alternate regional normalization schemes that can
account for difference in lung expansion rates.
PMID- 28519787
TI - SU-E-J-121: A New 4D Radiotherapy Planning Strategy Using Synthesized Tumor
Motion-Compensated Computed Tomography.
AB - PURPOSE: To validate a four-dimensional radiotherapy (4DRT) planning based on a
synthesized CT image compensating for tumor motion, accounting for tumor
rotation, deformation and distortion due to motion artifacts, and producing
realistic normal tissue density in motion-tracking beam eye view. METHODS: 4D
computed tomography (4DCT) images of six patients with peripheral lung lesions in
mid or lower lobs (motion range: 0.5-3.5cm and size: 1.5+/-2.0 cm3 ) were used. A
customized program was used for simulating the patient anatomy with a motion
compensated tumor using 4DCT by aligning the tumor and averaging the 4DCT into a
static 3.5DCT image. The gross tumor volume (GTV) was delineated
semiautomatically using a threshold algorithm. Variation of GTV in each phase CT
was assessed across all phases. 3DRT plans were generated using 3.5DCT and 4DCT
and compared for validation. An integrated dose volume histogram (iDVH) from all
phase plans and dose warping using deformable image registration (DIR) were used
for evaluating 4D plans and comparing with 3.5D plans. RESULTS: The range of
tumor volume variation over the mean within a breathing cycle was 87%+/-46%. The
3.5DCT produced an 'averaged' GTV, more reliable than that from any phase CT. The
results show that the 3.5D plan is equivalent to the 4D plan, except for low dose
area, using the iDVH evaluation. On average, the percentage difference for the
areas under the DVH and iDVH is 4.3%+/-2.7%, while 2/3 of the difference results
from low dose region blow D20%. Using DIR-based dose warping, PTV coverage varies
due to DIR uncertainty for the small lesions. CONCLUSIONS: The 3.5D plan is
equivalent to the 4D plan for peripheral lung lesions, yet requires much less
clinical workload. The 3.5D plan accounts for tumor motion and tumor variation
for a more reliable delineation, and for realistic normal tissue representation
for motion tracking.
PMID- 28519788
TI - SU-E-J-92: CERR: New Tools to Analyze Image Registration Precision.
AB - PURPOSE: To present new tools in CERR (The Computational Environment for
Radiotherapy Research) to analyze image registration and other software
updates/additions. METHODS: CERR continues to be a key environment (cited more
than 129 times to date) for numerous RT-research studies involving outcomes
modeling, prototyping algorithms for segmentation, and registration, experiments
with phantom dosimetry, IMRT research, etc. Image registration is one of the key
technologies required in many research studies. CERR has been interfaced with
popular image registration frameworks like Plastimatch and ITK. Once the images
have been autoregistered, CERR provides tools to analyze the accuracy of
registration using the following innovative approaches (1)Distance Discordance
Histograms (DDH), described in detail in a separate paper and (2)'MirrorScope',
explained as follows: for any view plane the 2-d image is broken up into a 2d
grid of medium-sized squares. Each square contains a right-half, which is the
reference image, and a left-half, which is the mirror flipped version of the
overlay image. The user can increase or decrease the size of this grid to control
the resolution of the analysis. Other updates to CERR include tools to extract
image and dosimetric features programmatically and storage in a central database
and tools to interface with Statistical analysis software like SPSS and Matlab
Statistics toolbox. RESULTS: MirrorScope was compared on various examples,
including 'perfect' registration examples and 'artificially translated'
registrations. for 'perfect' registration, the patterns obtained within each
circles are symmetric, and are easily, visually recognized as aligned. For
registrations that are off, the patterns obtained in the circles located in the
regions of imperfections show unsymmetrical patterns that are easily recognized.
CONCLUSIONS: The new updates to CERR further increase its utility for RT
research. Mirrorscope is a visually intuitive method of monitoring the accuracy
of image registration that improves on the visual confusion of standard methods.
PMID- 28519789
TI - SU-E-J-103: Characteristics of Bladder Wall Deformation as a Function of Bladder
Filling.
AB - PURPOSE: ICRU report 83 recommends delineation of the wall for hollow organs such
as the bladder. For image guided radiotherapy, there is no guidance as to how to
delineate deformed walls as the filling of hollow organs change. This work
investigates characteristics of bladder wall deformation as a function of bladder
filling in a controlled process. METHODS: CT images of a fresh pig bladder are
obtained in-air with different bladder air fillings. A plastic hose inserted into
and glued to the bladder neck forms an air-tight seal for filling with a syringe.
At each air-filling level, a helical CT (90kV, 90mAs) of the bladder is obtained.
The pixel size on all CT images is <0.5 mm. Images are imported into a commercial
planning system for delineation and statistical evaluation. Bladder walls at each
filling status are auto-contoured, then edited for quality assurance slice by
slice. The auto-contouring threshold is selected to obtain consistent volumes of
the resulting region-of-interest at each filling status. RESULTS: When the
bladder wall interior volume increases by 360 cm3 from injecting air, the wall
thickness decreases from 2.9 mm to 1.2 mm. The decrease in wall thickness is
accompanied by a decrease in the wall CT number. CONCLUSIONS: For a pig bladder,
the wall thickness decreases with increased air filling. The CT number (hence
apparent density) of the volume decreases as the bladder expands. Further
investigation is ongoing to determine if the apparent density decrease is real,
due to CT reconstruction, or due to the bladder being in an air, rather than
liquid environment. Characterization of hollow organ wall thickness variations
may be important for image guided radiation therapy and organ wall dose
evaluation. Support: P01CA116602.
PMID- 28519790
TI - SU-E-J-63: Feasibility Study of Proton Digital Tomosynthesis in Proton Beam
Therapy.
AB - PURPOSE: We investigated the feasibility of proton tomosynthesis as daily
positioning of patients and compared the results with photon tomosynthesis as an
alternative to conventional portal imaging or on-board cone-beam computed
tomography. METHODS: Dedicated photon-like proton beam using the passively
scattered proton beams by the cyclotron was generated for proton imaging. The
eleven projections were acquired over 30 degree with 3 degree increment in order
to investigate the performance of proton tomosynthesis. The cylinder blocks and
resolution phantom were used to evaluate imaging performance. Resolution phantom
of a cylinder of diameter 12 cm was used to investigate the reconstructed imaging
characteristics. Electron density cylinder blocks with diameter of 28 mm and
height of 70 mm were employed to assess the imaging quality. The solid water,
breast, bone, adipose, lung, muscle, and liver, which were tissue equivalent
inserts, were positioned around the resolution phantom. The images were
reconstructed by projection onto convex sets (POCS) algorithm and total variation
minimization (TVM) methods. The Gafchromic EBT films were utilized for measuring
the photon-like proton beams as a proton detector. In addition, the photon
tomosynthesis images were obtained for a comparison with proton tomosynthesis
images. The same angular sampling data were acquired for both proton and photon
tomosynthesis. RESULTS: In the resolution phantom image obtained proton
tomosynthesis, down to 1.6 mm diameter rods were resolved visually, although the
separation between adjacent rods was less distinct. In contrast, down to 1.2 mm
diameter rods were resolved visually in the reconstructed image obtained photon
tomosynthesis. Both proton and photon tomosynthesis images were similar in
intensities of different density blocks. CONCLUSIONS: Our results demonstrated
that proton tomosynthesis could make it possible to provide comparable tomography
imaging to photon tomosynthesis for positioning as determined by manual
registration of high density materials.
PMID- 28519791
TI - SU-E-J-94: Investigating the Use of Deformable Algorithms to Register MR Images
Acquired with and Without an Endo-Rectal Coil.
AB - PURPOSE: Magnetic resonance spectroscopic imaging (MRSI) can identify the
dominant intraprostatic lesion, which can then be boosted using high-dose rate
(HDR) brachytherapy. MRSI requires the use of an endo-rectal coil, which deforms
the prostate. We investigate the performance of deformable registration
algorithms to deform MR images acquired with an endo-rectal coil to images
acquired without a coil for HDR brachytherapy planning. METHODS: This study
utilized MR images of five HDR brachytherapy patients acquired with and without
an endo-rectal coil during the same MRSI imaging study. The prostate was
contoured on each set of 'Coil-In' and 'Coil-Out' MR images by an experienced
radiation oncologist. The 'Coil-In' and 'Coil-Out' images were rigidly aligned
such that the posterior margins of the prostate were as close as possible without
deformation. Variations on a commercially available deformation algorithm using
the B-spline method were applied to a volume of interest that surrounded the
prostate and excluded as much of the coil and rectum as possible. The Dice
similarity index (DSI) was calculated between rigidly registered contours (DSI1),
and compared to the DSI calculated between the 'Coil-In' contour and the contour
deformed from the 'Coil-Out' image to the 'Coil-In' image (DSI2). The difference
was calculated between DSI2 and DSI1, where a positive change in DSI would
indicate an improvement in contour agreement over rigid registration of the
prostate in the 'Coil-Out' and 'Coil-In' images. RESULTS: The B-spline
deformation algorithm designed specifically for MR images was most effective in
deforming the 'Coil-Out' to the 'Coil-In' prostate contour with a mean change in
DSI of 0.0124 with contrast correction, and 0.0004 without. CONCLUSIONS: Out of
six algorithms tested, only the MR-specific algorithm produced positive changes
in DSI. The accuracy of the deformation algorithm on mapping the internal
structures of the prostate between 'Coil-Out' and 'Coil-In' images is under
investigation. We acknowledge Velocity for providing the registration software.
PMID- 28519792
TI - SU-E-J-66: Evaluation of Proton Induced X-Ray Fluorescence from Gold Fiducial
Markers for In-Vivo Determination of Proton Range and Energy.
AB - PURPOSE: To evaluate a method for in-vivo determination of proton range and post
Bragg peak straggling by detection of proton induced x-ray fluorescence of
markers placed at known locations. METHODS: Therapeutic beams from the UF Proton
Therapy Institute were used to excite proton-induced x-ray fluorescence emission
(PIXE) from cylindrical pure gold fiducial markers. The markers were embedded in
a homogeneous water phantom and PIXE was measured using NaI photodetectors with
energy dispersive spectral analysis. The geometry of the phantom and marker
placement was chosen to model parallel-opposed beam treatment of prostate cancer
by proton therapy. The fluorescence yield from these markers was further modeled
using the GEANT4 Monte-Carlo package with low-energy corrections. Gold K and L
shell fluorescence yield as determined by the GEANT4 simulations was verified
quantitatively by comparison to measured Au yield at energies from 1 MeV to 68
MeV, and to semiempirical model calculations covering the energy range from 1 MeV
to 15 MeV. RESULTS: The Au K-shell fluorescence cross section is significantly
smaller thanthat of the L-shell, but the higher yield of the L-shell fluorescence
isoffset by the larger absorption as the x-ray exits the phantom. The
overallrelative detection efficiency of K and L shell fluorescence depends on
thedetails of the shape of the phantom and location of the marker.
Acharacteristic shape of fluorescence yield as it depends on proton range
isfound, which can be used to extract an in-vivo PDD profile of a spread-outBragg
peak (SOBP). CONCLUSIONS: A combination of a specific protocol for delivering a
SOBP, geometriclocation of fiducial markers from CT, and simultaneous detection
of protoninduced x-ray fluorescence, can determine the depth range of a primary
protonbeam in-vivo. The fluorescence yield as measured at the Proton Therapy
Institute is easily distinguished from background radiation.
PMID- 28519794
TI - SU-E-J-77: Clinical Evaluation of a Three-Dimensional Optical Surface Based
Imaging Device for Breast Treatment Setup.
AB - PURPOSE: The purpose of this work is to evaluate the accuracy of a three
dimensional surface based optical imaging device for treatment setup of breast
patients. A commercial system has been used to acquire live surface contour data,
which are registered with a reference surface contour for setup corrections. This
work is to investigate the accuracy of this system when compared with
conventional portal images. METHODS: The system was clinically applied to twenty
breast cancer patients receiving radiotherapy treatment. For each patient,
conventional portal imaging before the first fraction was acquired and approved
by clinicians. After approval of portal images, a reference surface contour was
acquired. This reference contour was subsequently used to guide daily patient
setup followed by weekly portal images. A total of 89 sets of portal images were
acquired for these patients. On days when portal images were taken, optical
images were used to guide for initial patient setup, then portal images were
taken and evaluated in order to make direct comparison between the optical
imaging system and the conventional portal images. RESULTS: Among 89 sets of
portal images taken after optical imaging guidance, 11 (12%) sets of portal
images required further adjustments in order to achieve clinically acceptable
criteria. The average vector adjustments for these 11 fractions were 0.65 cm +/-
0.30 cm. Average vector shifts made according to the optical imaging for all
fractions of 20 patients was 0.66 +/- 0.33 cm. CONCLUSIONS: Our data show that
the commercial optical system can improve the accuracy of treatment setup for
breast patients without additional radiation exposure. The observed discrepancy
between the portal images and optimal images requires further investigation. The
optical imaging guidance can be routinely used between normally scheduled portal
imaging.
PMID- 28519793
TI - SU-E-J-105: Evaluating Auto-Contouring of Prostate KV Conebeam CTs.
AB - PURPOSE: Auto-contouring of daily kV conebeam CTs (kVCBCT) is critical for online
adaptive radiotherapy. We surveyed a set of geometric and dosimetric measures to
determine which best assess the suitability of kVCBCT contouring algorithms for
use in prostate region adaptive planning. METHODS: Six patients with daily kVCBCT
undergoing IMRT of the prostate to 78 Gy were selected. Dose was recalculated
with patient density forced to water. Contours were generated on nine kVCBCT for
each patient using ABAS (Elekta Ltd.) and also by a physician. The prostate mean
dose, D100, D98, where determined and V70 (% and cc) and mean dose for the
bladder and rectum for both physician and auto contours. The Dice's Coefficient
(DC) was calculated between auto and physician contours, as well as a restricted
DC (rDC) which combines geometric and dosimetric information by comparing only
the volume within a high dose region. RESULTS: Prostate accuracy can only be
discerned with D100, additionally there is no correlation (R2=0.036) between D100
and DC. For all organs, mean dose does not reflect contour suitability. There is
large variation in V70 (% and cc) for rectum and bladder, implying V70 is a
sensitive indicator of contour suitability. There is however no correlation of
V70 with DC. A dose region (>57 Gy) to calculate rDC was chosen to provided
optimal correlation (R2>0.81) to V70 (% and cc, rectum and bladder). CONCLUSIONS:
V70 for rectum and bladder shows the most sensitivity to contour suitability, by
concentrating on where accuracy is most vital. Prostate contouring is less
critical due to treatment margins, D100 provides the most discerning metric. DC
and mean dose are not useable. In lieu of V70, rDC could be used. The rDC can be
approximated by limiting to within 2-3 cm of the prostate contour, alleviating
the need to calculate dose. A research version of ABAS was provided by Elekta.
PMID- 28519795
TI - SU-E-J-116: Investigation of Accuracy and Precision of ITV Delineation by PET SUV
Threshold.
AB - PURPOSE: To determine PET SUV values in Pinnacle TPS and to assess the accuracy
and precision of the ITV according to SUV thresholds. The goal is to minimize
errors in target definition by using SUV showing enhanced metabolic activity of
the tumor and fast CT imaging with less motion artifacts. METHODS: Mean PET
values in individual patients were obtained from statistics of body contours for
whole body PET-CT scans. The SUVs were calculated by normalizing the PET values
in any voxel by the mean body PET value. These clinically acquired SUVs were
plotted against values reported at the time of the scan for verification. GTVs
were contoured on petCT scans and the ITV's were contoured using three published
methods of SUV thresholds at 2.5, at ratio of 40 percent of the maximum, and 30
percent of the maximum added to 60 percent of the mean body. GTV volumes were
plotted against the 3 sets of ITVs to investigate their relationships. RESULTS:
Examination of 11 patients showed a strong linear relationship between clinically
determined SUVs and those reported; indicating the validity of our SUV
definition. Plots of GTV volumes versus ITV volumes for each of the 3 thresholds
revealed a less clear relationship. The effectiveness of each method to generate
a reasonable ITV was highly patient dependent; in general the 2.5 threshold gave
the best results, while the 40 percent maximum produced the worst. CONCLUSIONS:
While more data is required to make a definitive statement about the value of PET
SUV threshold defined ITVs, the findings do seem to reveal a pattern between GTV
and ITV size. If an appropriate SUV threshold is chosen, the GTV-ITV volume
relationship is nearly linear, which suggests extending the GTV in volume rather
than the margin distance as is common in ITV delineation.
PMID- 28519796
TI - SU-E-J-88: Deformable Registration Using Multi-Resolution Demons Algorithm for
4DCT.
AB - PURPOSE: In order to register 4DCT efficiently, we propose an improved deformable
registration algorithm based on improved multi-resolution demons strategy to
improve the efficiency of the algorithm. METHODS: 4DCT images of lung cancer
patients are collected from a General Electric Discovery ST CT scanner from our
cancer hospital. All of the images are sorted into groups and reconstructed
according to their phases, and eachrespiratory cycle is divided into 10 phases
with the time interval of 10%. Firstly, in our improved demons algorithm we use
gradients of both reference and floating images as deformation forces and also
redistribute the forces according to the proportion of the two forces.
Furthermore, we introduce intermediate variable to cost function for decreasing
the noise in registration process. At the same time, Gaussian multi-resolution
strategy and BFGS method for optimization are used to improve speed and accuracy
of the registration. To validate the performance of the algorithm, we register
the previous 10 phase-images. We compared the difference of floating and
reference images before and after registered where two landmarks are decided by
experienced clinician. We registered 10 phase-images of 4D-CT which is lung
cancer patient from cancer hospital and choose images in exhalationas the
reference images, and all other images were registered into the reference images.
RESULTS: This method has a good accuracy demonstrated by a higher similarity
measure for registration of 4D-CT and it can register a large deformation
precisely. Finally, we obtain the tumor target achieved by the deformation fields
using proposed method, which is more accurately than the internal margin (IM)
expanded by the Gross Tumor Volume (GTV). Furthermore, we achieve tumor and
normal tissue tracking and dose accumulation using 4DCT data. CONCLUSIONS: An
efficient deformable registration algorithm was proposed by using multi
resolution demons algorithm for 4DCT.
PMID- 28519797
TI - SU-E-J-98: 3D Tracking of Interfraction Patient Setup Uncertainties Using
Multiple Kinect Sensors.
AB - PURPOSE: On-board optical 3D imaging enables measuring daily setup patient
uncertainties without involving any additional imaging-induced radiation dose to
critical structures. We hypothesize that the tumor and normal organ deformation
caused by routine patient head and neck misalignments can be determined by
coupling a quantitative patient-specific biomechanical model with quantitative
skin surface 3D imaging. METHODS: A set of 3D cameras are used to track the
patient anatomy externally. One of the cameras employed a marker less face
recognition and tracking for delineating the region of the patient's face. The
location of the face was then shared among the camera controllers in real-time
and the anatomical contour that closely matches the face region is selected and
integrated to form a single 3D anatomical representation. Patient surface
aligning was performed between the patient's external surface obtained from a
reference 3D anatomy (simulation CT, MRI, patient surface map from previous
fraction) and the above-mentioned camera system to quantify the daily patient
setup variations. For each of the 3D patient surface, a point feature histogram
(PFH) was first generated. Once the PFH descriptors were generated, a non-rigid
iterative closest point registration algorithm that minimizes the difference in
the PFH descriptor aligns the patient surface to the reference 3D anatomy.
RESULTS: The proposed tracking system was able to track both the patient surface
setup uncertainty and the internal anatomy when coupledwith a patient specific
biomechanical head and neck model. CONCLUSIONS: A 3D head and neck tracking
system that monitors the interfraction patient setup uncertainties in the head
and neck cancer patient is presented. The aligning process was shown to perform
for cases with and without the head immobilization system. The external patient
surface manifold and the motion vectors will be coupled to align the
biomechanical model using model-guided techniques.
PMID- 28519798
TI - SU-E-J-70: A Study of the Correlation of 3D Surface Matching and KV Imaging for
Chestwall IMRT.
AB - PURPOSE: We investigated the accuracy of surface matching compared to kV
positioning of 10 post-mastectomy chestwall patients receiving inverse-planned,
non-gated IMRT. METHODS: During 130 treatment sessions, non-gated 3D surfaces
were captured using AlignRT (v4.5) before and after table translations as
indicated by kV imaging. Surfaces were compared to a reference generated from CT
data. Pearson's correlations between 'indicated' AlignRT and kV shifts were
studied for surface registration of user-defined regions-of-interest (ROIs): the
entire surface ('all') and the chestwall ('cw'). In 21% of sessions, two
consecutive surfaces of patients in identical positions were used to estimate
variability. Finally, the 'implemented' shifts detected by AlignRT were
calculated and compared to the absolute table translations. RESULTS: Correlations
between 'indicated' AlignRT and kV shifts were higher for 'cw' than for 'all':
r=0.65 (Anterior-Posterior), r=0.65 (Superior-Inferier), r=0.44 (Left-Right).
Correlations exhibited large inter-patient variability; 60% had r<0.6 in at least
1 direction thereby resulting in ow correlation between 3D Euclidian shift
distances (r=0.48). Correlations between 'cw' and kV increased (r>0.8) for
'implemented' table shifts; only 2 patients demonstrated r<0.6 in any single
direction. Comparison of consecutively-acquired 'cw' surfaces controlled for
patient movement demonstrated standard deviations (STDs) of: 1.2mm (A-P), 2.0mm
(S-I), 1.6mm (L-R). While STDs between 'implemented' and kV shifts were on the
same order, STDs between 'indicated' and kV shifts were twice as large: 2.9mm (A
P), 3.5mm (S-I), 4.1mm (L-R). Rotational differences >1degree were calculated
more often when registering 'cw' (22%) than 'all' (5%). At the treatment
position, residual STDs remained high (3.0-3.6mm). CONCLUSIONS: On average, 'cw'
shifts correlated with kV shifts but exhibited significant inter-patient
variability and larger rotations than 'all'. Differences between AlignRT and kV
were ~3mm for initial patient positioning. The lack of a one-to-one
correspondence between surface and kV shifts in any single session must be
further investigated before clinical implementation.
PMID- 28519799
TI - SU-E-J-109: Accurate Contour Transfer Between Different Image Modalities Using a
Hybrid Deformable Image Registration and Fuzzy Connected Image Segmentation
Method.
AB - PURPOSE: To develop and evaluate a tool that can improve the accuracy of contour
transfer between different image modalities under challenging conditions of low
image contrast and large image deformation, comparing to a few commonly used
methods, for radiation treatment planning. METHODS: The software tool includes
the following steps and functionalities: (1) accepting input of images of
different modalities, (2) converting existing contours on reference images (e.g.,
MRI) into delineated volumes and adjusting the intensity within the volumes to
match target images (e.g., CT) intensity distribution for enhanced similarity
metric, (3) registering reference and target images using appropriate deformable
registration algorithms (e.g., B-spline, demons) and generate deformed contours,
(4) mapping the deformed volumes on target images, calculating mean, variance,
and center of mass as the initialization parameters for consecutive fuzzy
connectedness (FC) image segmentation on target images, (5) generate affinity map
from FC segmentation, (6) achieving final contours by modifying the deformed
contours using the affinity map with a gradient distance weighting algorithm. The
tool was tested with the CT and MR images of four pancreatic cancer patients
acquired at the same respiration phase to minimize motion distortion. Dice's
Coefficient was calculated against direct delineation on target image. Contours
generated by various methods, including rigid transfer, auto-segmentation,
deformable only transfer and proposed method, were compared. RESULTS: Fuzzy
connected image segmentation needs careful parameter initialization and user
involvement. Automatic contour transfer by multi-modality deformable registration
leads up to 10% of accuracy improvement over the rigid transfer. Two extra
proposed steps of adjusting intensity distribution and modifying the deformed
contour with affinity map improve the transfer accuracy further to 14% averagely.
CONCLUSIONS: Deformable image registration aided by contrast adjustment and fuzzy
connectedness segmentation improves the contour transfer accuracy between multi
modality images, particularly with large deformation and low image contrast.
PMID- 28519800
TI - SU-E-J-81: Beveled Needle Tip Detection Error in Ultrasound-Guided Prostate
Brachytherapy.
AB - PURPOSE: To quantify the needle tip detection errors in ultrasound images due to
bevel-tip orientation in relation to the location on template grid. METHODS:
Transrectal ultrasound (TRUS) system (BK Medical) with physical template grid and
18-gauge bevel-tip (20-deg beveled angle) brachytherapy needle (Bard Medical,
Covington, GA) were used. The TRUS was set at 6.5MHz in water phantom at 40
degrees C and measurements were taken with 50% and 100% TRUS gains. Needles were
oriented with bevel-tip facing up (0-degree) and inserted through template grid
holes. Reference needle depths were measured when needle tip image intensity was
bright enough for potentially consistent readings. High-resolution digital
vernier caliper was used to measure needle depth. Needle bevel-tip orientation
was then changed to bevel down (by rotating 180-degree) and needle depth was
adjusted by retracting so that the needle-tip image intensity appeared similar to
when the needle bevel-tip was at 0-degree orientation. Clinically relevant
locations were considered for needle placement on the template grids (1st row to
9th row, and 'a-f' columns). RESULTS: For 50% TRUS gain, bevel tip detection
errors/differences were 0.69+/-0.30mm (1st row) to 3.23+/-0.22mm (9th row) and
0.78+/-0.71mm (1st row) to 4.14+/-0.56mm (9th row) in columns 'a' and 'D',
respectively. The corresponding errors for 100% TRUS gain were 0.57+/-0.25mm to
5.24+/-0.36mm and 0.84+/-0.30mm to 4.2+/-0.20mm in columns 'a' and 'D',
respectively. These errors/differences varied linearly for grid-hole locations on
the rows and columns in between, smaller to large depending on distance from the
TRUS probe. Observed no effect of gains (50% vs. 100%) along 'D' column, which
was directly above the TRUS probe. CONCLUSIONS: Experiment results revealed that
the beveled needle tip orientation could significantly impact the detection
accuracy of the needle tips, based on which the seeds might be delivered. These
errors may lead to considerable dosimetric deviations in prostate brachytherapy
seed implantation.
PMID- 28519801
TI - SU-E-J-120: Characterization of 4D Lung Ventilation Based on 4DCT Lung Density.
AB - PURPOSE: To characterize patient's 4D lung ventilation and motion using 4DCT
images aiming to extract pulmonary features for developing a biomechanical model
to predict lung tumor motion. METHODS: 4DCT images of sixteen patients were used
for initial 4D-ventilation evaluation. A program was developed for visualization
and quantification of 4D lung ventilation. Lung density gradient and pleural
pressure variation were evaluated based on the gravity. Freeform deformable image
registration (DIR) was applied to map the lung density from one phase to another,
with linearly interpolated voxel density. The warped lung density from a
secondary CT was compared with the primary CT (full-exhalation) for
quantification. To minimize the uncertainty from motion artifacts for
quantitative ventilation/motion analysis, we developed two screening algorithms
(based on Fourier Transformation and Generalized Linear Regression) to quantify
the regularity (score: 0 to 1) of the RPM waveform, assuming the higher the
regularity in RPM the less motion artifacts in 4DCT. Ninety-seven RPM curves (54
free-breathing and 43 audio-coaching patients) were used to qualitatively test
these screening methods. RESULTS: Lung density gradient in anterior-posterior
direction for supine patients is observed in 15/16 patients at scale of >100
200HU. The gravity pressure due to lung tissue weight is estimated to be ~4mmHg,
which could neutralize the pleural pressure at the posterior chest wall. The
different pleural pressures at anterior/posterior chest walls may explain the
difference in local diaphragm muscle engagement and motion range: 8+/-5mm
(anterior) and 23+/-12mm (posterior). Motion artifacts and DIR uncertainty
affected quantitative ventilation mapping. In the RPM regularity assessment,
audiocoaching patients score higher than free-breathing patients: 0.76+/-0.13 vs.
0.50+/-0.19 (Fourier method) and 0.74+/-0.19 vs. 0.66+/-0.17 (Regression method).
High-quality 4DCTs can be readily selected for further quantitative
ventilation/motion analysis. CONCLUSIONS: We have characterized several basic
features of lung ventilation and motion and developed two effective screening
methods for high-quality 4DCT for on-going quantitative studies.
PMID- 28519802
TI - SU-E-J-91: FFT Based Medical Image Registration Using a Graphics Processing Unit
(GPU).
AB - PURPOSE: To evaluate the efficiency gains obtained from using a Graphics
Processing Unit (GPU) to perform a Fourier Transform (FT) based image
registration. METHODS: Fourier-based image registration involves obtaining the FT
of the component images, and analyzing them in Fourier space to determine the
translations and rotations of one image set relative to another. An important
property of FT registration is that by enlarging the images (adding additional
pixels), one can obtain translations and rotations with sub-pixel resolution. The
expense, however, is an increased computational time. GPUs may decrease the
computational time associated with FT image registration by taking advantage of
their parallel architecture to perform matrix computations much more efficiently
than a Central Processor Unit (CPU). In order to evaluate the computational gains
produced by a GPU, images with known translational shifts were utilized. A
program was written in the Interactive Data Language (IDL; Exelis, Boulder, CO)
to performCPU-based calculations. Subsequently, the program was modified using
GPU bindings (Tech-X, Boulder, CO) to perform GPU-based computation on the same
system. Multiple image sizes were used, ranging from 256*256 to 2304*2304. The
time required to complete the full algorithm by the CPU and GPU were benchmarked
and the speed increase was defined as the ratio of the CPU-to-GPU computational
time. RESULTS: The ratio of the CPU-to- GPU time was greater than 1.0 for all
images, which indicates the GPU is performing the algorithm faster than the CPU.
The smallest improvement, a 1.21 ratio, was found with the smallest image size of
256*256, and the largest speedup, a 4.25 ratio, was observed with the largest
image size of 2304*2304. CONCLUSIONS: GPU programming resulted in a significant
decrease in computational time associated with a FT image registration algorithm.
The inclusion of the GPU may provide near real-time, sub-pixel registration
capability.
PMID- 28519803
TI - SU-E-J-102: The Impact of the Number of Subjects for Atlas-Based Automatic
Segmentation.
AB - PURPOSE: To determine the impact of atlas size on the performance of atlas-based
automatic segmentation (ABAS) in delineation of organs at risk for adaptive
radiation therapy. METHODS: A total of 25 patients who had undergone intensity
modulated radiation therapy for various head and neck cancers were
retrospectively selected for inclusion in a library to be used for ABAS with the
MIM VISTA software package (MIM Software, Cleveland OH). Treatment planning
computed tomography (CT) scans and subsequent organ at risk (OAR) contours
generated as part of the treatment planning process for these patients were added
to the library. This library of 25 patients was then successively pruned to
generate 5 atlases with 25, 20, 15, 10, and 5 patient subjects respectively.
Atlas based segmentation was performed on 10 retrospectively selected treatment
planning CT scans to automatically generate right and left parotid glands and
brainstem contours. These planning CT scans belonged to a unique set of 10
patient subjects different from the ones used for generating the atlases. One
physician (JW), who was blinded to the ABAS results, manually delineated gold
standard contours for the right and left parotid glands and brainstem. Dice
similarity coefficients were calculated and analyzed as a function of atlas
subject size. RESULTS: For the sites selected in this study, the performance of
ABAS was relatively insensitive to atlas size. Furthermore, some patient subjects
were repeatedly selected implying that the adoption of a single standard patient
for ABAS may be of benefit. CONCLUSIONS: Our preliminary results indicate that
the performance of the atlas based segmentation module in MIM VISTA Version 5.2
for the organs studied here may be relatively insensitive to the atlas size.
PMID- 28519804
TI - SU-E-J-74: Evaluation of the Commercial Prototype Open Face Mask Used with
Surface Rendering Imaging System for Proton Therapy Patients with Cancers of the
Brain and Head: Successful Preclinical Study.
AB - PURPOSE: Evaluation of the commercial prototype open face mask (Fibreplast, Q
FixTM) used with surface rendering imaging system (AlignRTTM, London, UK) for
setup and monitoring of proton therapy patients with cancers of the brain and
head. METHODS: Fibreplastic open face masks were used with Base-of-Skull
frame/moldcare pillow. Two sizes of the pre-made cutouts in the masks were
investigated: leaveing open skin surface in the oval-shaped area between (I)
upper lip and forehead boss, II) between mandible and forehead boss in superior
inferior direction; and between zygomatic (cheek-) bones/sphenoid bones
laterally. Calibration of AlignRT system was verified with SRS cube phantom
(VisionRT)and 2D X-ray patient positioning system (DIPS, IBA). The accuracy of
translational shifts and rotations was a) verified using a head&neck phantom and
b) tested using volunteers. Within AlignRT software, only the open area was used
as ROI for the registration; the option 'Intracranial SRS' used for surface
capture. RESULTS: For the isocenter determination accuracy within 0.3mm/0.2
degrees, the head&neck phantom registration was performed with the 0.5mm/0.5
degree accuracy; the volunteer tests showed the registration accuracy within
0.5mm +/-0.2mm (1 s)/0.7+/-0.2 (1 s) degree. The simulation of the noise in the
surface data such as eye blinking and attempts to swallow/chew was performed,
with negligible effect on the registration. No significant differences between
the study results between the masks of type (I) and (II) were noticed.
CONCLUSIONS: The AlignRT surface rendering system has sufficient accuracy when
used with the open face head&neck mask for localization/registration of the
proton therapy patients with tumors of the head and brain.
PMID- 28519805
TI - SU-E-J-113: A New Quantification Measure of the Difference Between Two Organ
Contours.
AB - PURPOSE: To develop a measuring method between two contours, which can be used
for validating a PTV during IGRT, organ motion and/or deformation studies.
METHODS: Quantifying the geometric difference between two organ/target surfaces
is essential for Radiation therapy planning and delivery. Point-to-surface
distance measures have been utilized to evaluate and visualize the local surface
differences. However, previously well-known distance measures have critical
shortfalls. Normal distance (ND) measure suffers when the reference surface is
strongly curved. Minimum distance (MD) measure (a.k.a. Hausdorff distance)
suffers when the test surface is strongly curved. Our new distance measure named
Error-Proof Distance (EPD) can deal with both difficult cases.EPD measure
calculates the maximum value between the Forward Minimum Distance (FMinD) and the
Backward Maximum Distance (BMaxD) at each point. The FMinD denotes the minimum
distance to the test surface from a point on the reference surface. The BMaxD
means the maximum value among the minimum distances from all points of the test
surface to the point on the reference surface. We tested EPD using three 2-D
contour examples including a 20mm shifted contour, and two 3-D clinical cases.
RESULTS: In case of 2-D contour examples, ND and MD measure failed in strongly
curved areas, but EPD measure outperformed the others. The maximum distance
measured between a reference and a 20mm shifted test contour should be equal to
20mm, but ND erroneously measured 24mm. Furthermore, ND reported erroneous
distances where the reference surface is strongly curved in 3-D clinical cases.
CONCLUSIONS: We succeeded to prove that a new EPD is arobust and accurate
distance measure to compare two 2D or 3D surfaces. EPD measure can be used to
evaluate and visualize the surface difference of organ contours. It is also
helpful for proving PTV margin during IGRT, and organ motion and/or deformation
studies. This project is partially supported by the Agency for Healthcare
Research and Quality (AHRQ) grant 1R18HS017424-01A2.
PMID- 28519806
TI - SU-E-J-62: Comparison of Brainlab ExacTrac, AlignRT, and CBCT Positional Accuracy
for SRS Set-Up on a TrueBeam STx.
AB - PURPOSE: To compare the ability of Brainlab ExacTrac (Brainlab AG, Feldkirchen,
Germany) x-ray (XRAY), Brainlab infrared array (IR), cone beam CT (CBCT), and
AlignRT (VisionRT Ltd., London, UK) to accurately measure patient displacement
during stereotactic radiosurgery (SRS) on a Varian TrueBeam STx (Varian Inc, Palo
Alto, CA). METHODS AND MATERIALS: A CT scan was obtained for a custom skull
phantom placed in a Brainlab frameless SRS immobilization system with the
Brainlab CT localizer box attached. A generic plan was created in Brainlab iPlan
and sent to Brainlab ExacTrac, to AlignRT, and to the TrueBeam. The skull phantom
was set-up on the TrueBeam and positioned to isocenter using XRAY. Next, CBCT and
IR were acquired and evaluated to determine baseline positions for these methods.
A new AlignRT reference surface was acquired as baseline. The phantom was then
displaced 2 mm in the vertical, lateral, and longitudinal dimensions using the
TrueBeam couch (the couch tolerance is 0.1 mm in each dimension). New XRAY, IR,
CBCT, and AlignRT data was acquired in this position. RESULTS: Initially, all
methods found that the phantom was positioned with < 0.3 mm accuracy. After the
shiftes, XRAY suggested shifts were 2.0, 2,1, 1.8 mm in the vertical,
longitudinal, and lateral dimensions, respectively. The IR shifts were 1.7, 2.6,
2.1 mm. The CBCT shifts were 1.8, 1.8, 2.1 mm. The AlignRT shifts were 2.2, 1.6,
1.4 mm. CONCLUSION: The internal XRAY and CBCT methods produced slightly better
agreement with the table shifts. The external IR and AlignRT methods were less
accurate, but still gave agreement of <= 0.6 mm. Note, the AlignRT cameras did
not produce a clean surface off of the phantom. Improved accuracy is expected
from a skin surface. This is preliminary work, more extensive study is needed to
evaluate these methods.
PMID- 28519808
TI - SU-E-J-104: Evaluation of Atlas-Based Auto-Segmentation on Daily In-Room CT for
Prostate Cancer.
AB - PURPOSE: Anatomy delineation is a major time consuming task to correct for inter
fractional changes in anatomy. Atlas-based auto-segmentation (ABAS) was developed
to expedite this process. This study aims to evaluate the performance of ABAS
applying to high quality verification CT-imaging acquired using a CT-on-rail
system for prostate cancer. METHODS: The prostate, rectum and bladder were
manually contoured for seven prostate cancer patients. For each patient, three
patient specific atlases were generated consisting of one, four and seven prior
image and contour sets. ABAS was applied using these atlases for the last seven
daily CT images of each patient. The auto- and manual-contours were compared both
geometrically and dosimetrically. The reproducibility of the observation was
validated by an experienced radiation oncologist performing the same procedure.
The performance of ABAS with patient and non-patient specific atlases were also
evaluated on 21 image sets. P<0.05 was considered statistical significant for two
tailed paired student t-test. RESULTS: Contours obtained from ABAS agreed well
with the manual ones. With 1-image set atlas, the OI and DSC for the bladder were
greater than 96% and 91%, respectively. Both indices were above 81% for rectum
and prostate. The consistencies significantly improved by including 4 image sets
in the atlas, while a further increase of atlas size to 7 did not show obvious
benefits. Dose coverage for the auto- and manual-contours was similar for all
organs. Similar results were obtained by the second observer. Compared with non
patient specific atlas, patient specific atlas yielded more accurate contours.
The time for ABAS and manual contouring was ~2 min and ~20 min per image set,
respectively. CONCLUSIONS: With diagnostic quality verification images, ABAS can
provide fast and accurate delineations for prostate cancer on a daily basis. The
inclusion of more than one CT set in atlas improves the contouring results.
PMID- 28519807
TI - SU-E-J-65: Feasibility Study of Backscatter Imaging for Image-Guided
Radiotherapy.
AB - PURPOSE: Tracking tumor motion during external beam radiation therapy is a major
factor limiting the treatment of lung tumors. Several tracking techniques have
been previously reported; however, these are limited to 2D motion, fail to
capture image data during treatment delivery (e.g., patient setup imaging), fail
to capture motion along the beam axis (MV CineMode), or increase patient dose (kV
fluoroscopy). Creating images from radiation that is naturally scattered from the
patient during treatment could overcome the limitations of other techniques. This
study investigated the feasibility of using photon scatter to create images
during external beam radiation delivery. METHODS: A prototype imager was created
using a Trilogy Linac, pinhole collimator, and computed radiography (CR) plate.
Two small cylinders (solid water and cerrobend) were placed in the path of a 6MV
beam. The collimator/CR plate was placed at 45 degrees and 90 degrees from the
gantry head and 2000MU was delivered. Optically-stimulated luminescent (OSLD)
detectors were placed on the surface of the CR plate to measure photon dose.
Contrast-to-noise ratios (CNR) were calculated for each peg to assess image
quality. RESULTS: At 45 degrees , OSLD dose was 1.3+/-0.2cGy and the CNRs were
1.5 and 5.3 for water and cerrobend, respectively. OSLD dose increased to 2.6+/
0.3cGy and CNR increased to 14.8 and 18.3 at 90 degrees . Scatter from the gantry
head and the pinhole collimator are the major sources of noise which limit image
quality. The measured CNR satisfied the Rose criteria for detectability (CNR > 3
5) for the 90 degrees gantry orientation. Further, scatter imaging should
satisfy the Rose criteria if output is reduced from 2000MU to 200MU. CONCLUSIONS:
Preliminary results confirm the feasibility of using scatter imaging for in situ
treatment monitoring. Future work will investigate creation of tomosynthesis
images and improving image quality using increased shielding and a multi-pinhole
collimator.
PMID- 28519809
TI - SU-E-J-76: Clinical Use of a Real-Time Surface Image-Guided Positioning and
Tracking System in Proton Therapy.
AB - : Topic of interest: Clinical applications of AlignRT 3-cameras real-time surface
image-guided positioning system (IGPS) for positioning patients to reduce the
number of X-ray images and tracking intra-fractional movements in proton therapy.
PURPOSES: To position patients and track the intra-fractional movements, the
AlignRT system was implemented in proton incline-beam-line (IBL) at Procure
Oklahoma-City center. METHODS: The AlignRT3c system was configured near
perpendicular to the gantry rotation for accommodating the X-ray IGPS. To
evaluate positioning accuracy, more than 10 surfaces of each patient for ten
patients with intracranial tumors were acquired after patients positioned by X
ray IGPS. Displacements between acquired surfaces and the reference surface taken
at 1st day of treatment were examined. Intra-fractional movements with
respiratory was studied with gated surface that allows setting the reference
surface for patient at exhale during breathing. Intra-fractional movements due to
respiratory were monitored on 10 sections of each patient for three patients with
thoracic tumors. RESULTS: Accuracy of positioning patient is 2.0 mm at both
anterior-posterior and lateral directions, and is 3.5 mm in superior-inferior
(SI) direction by aligning the surfaces of masks. Observed larger displacements
along SI direction can be due to patient's movements within the mask. Periodical
displacements within 5 mm compared to its reference were seen for the three
patients with thorax tumors. However, 10 mm sharp displacements with a few
seconds were observed when patient moved the body. CONCLUSIONS: We have
implemented the first AlignRT3c IGPS for proton therapy for positioning patients
within 2.0 mm, and successfully tracked intra-fractional respiratory motion
during treatment after positioning patient.
PMID- 28519810
TI - SU-E-J-115: Graticule for Verification of Treatment Position in Neutron Therapy.
AB - PURPOSE: Until recently the treatment verification for patients undergoing fast
neutron therapy at our facility was accomplished through a combination of neutron
beam portal films aligned with a graticule mounted on an orthronormal x-ray tube.
To eliminate uncertainty with respect to the relative positions of the x-ray
graticule and the therapy beam, we have developed a graticule which is placed in
the neutron beam itself. METHODS: For a graticule to be visible on the portal
film, the attenuation of the neutron beam by the graticule landmarks must be
significantly greater than that of the material in which the landmarks are
mounted. Various materials, thicknesses, and mounting points were tried to gain
the largest contrast between the graticule landmarks and the mounting material.
RESULTS: The final design involved 2 inch steel pins of 0.125 inch diameter
captured between two parallel plates of 0.25 inch thick clear acrylic plastic.
The distance between the two acrylic plates was 1.625 inches, held together at
the perimeter with acrylic sidewall spacers. This allowed the majority of length
of the steel pins to be surrounded by air. The pins were set 1 cm apart and
mounted at angles parallel to the divergence of the beam dependent on their
position within the array. The entire steel pin and acrylic plate assembly was
mounted on an acrylic accessory tray to allow for graticule alignment.
CONCLUSION: Despite the inherent difficulties in attenuating fast neutrons, our
simple graticule design produces the required difference of attenuation between
the arrays of landmarks and the mounting material. The graticule successfully
provides an in-beam frame of reference for patient portal verification.
PMID- 28519811
TI - SU-E-J-87: Building Deformation Error Histogram and Quality Assurance of
Deformable Image Registration.
AB - PURPOSE: To quantify the systematic error of a Deformable Image Registration
(DIR) system and establish Quality Assurance (QA) procedure. METHODS: To address
the shortfall of landmark approach which it is only available at the significant
visible feature points, we adapted a Deformation Vector Map (DVM) comparison
approach. We used two CT image sets (R and T image sets) taken for the same
patient at different time and generated a DVM, which includes the DIR systematic
error. The DVM was calculated using fine-tuned B-Spline DIR and L-BFGS optimizer.
By utilizing this DVM we generated R' image set to eliminate the systematic error
in DVM,. Thus, we have truth data set, R' and T image sets, and the truth DVM. To
test a DIR system, we use R' and T image sets to a DIR system. We compare the
test DVM to the truth DVM. If there is no systematic error, they should be
identical. We built Deformation Error Histogram (DEH) for quantitative analysis.
The test registration was performed with an in-house B-Spline DIR system using a
stochastic gradient descent optimizer. Our example data set was generated with a
head and neck patient case. We also tested CT to CBCT deformable registration.
RESULTS: We found skin regions which interface with the air has relatively larger
errors. Also mobile joints such as shoulders had larger errors. Average error for
ROIs were as follows; CTV: 0.4mm, Brain stem: 1.4mm, Shoulders: 1.6mm, and Normal
tissues: 0.7mm. CONCLUSIONS: We succeeded to build DEH approach to quantify the
DVM uncertainty. Our data sets are available for testing other systems in our web
page. Utilizing DEH, users can decide how much systematic error they would
accept. DEH and our data can be a tool for an AAPM task group to compose a DIR
system QA guideline. This project is partially supported by the Agency for
Healthcare Research and Quality (AHRQ) grant 1R18HS017424-01A2.
PMID- 28519812
TI - SU-E-J-97: Evaluation of Multi-Modality (CT/MR/PET) Image Registration Accuracy
in Radiotherapy Planning.
AB - PURPOSE: Evaluate accuracy of multi-modality image registration in radiotherapy
planning process. METHODS: A water-filled anthropomorphic head phantom containing
eight 'donut-shaped' fiducial markers (3 internal + 5 external) was selected for
this study. Seven image sets (3CTs, 3MRs and PET) of phantom were acquired and
fused in a commercial treatment planning system. First, a narrow slice (0.75mm)
baseline CT scan was acquired (CT1). Subsequently, the phantom was re-scanned
with a coarse slice width = 1.5mm (CT2) and after subjecting phantom to
rotation/displacement (CT3). Next, the phantom was scanned in a 1.5 Tesla MR
scanner and three MR image sets (axial T1, axial T2, coronal T1) were acquired at
2mm slice width. Finally, the phantom and center of fiducials were doped with 18F
and a PET scan was performed with 2mm cubic voxels. All image scans (CT/MR/PET)
were fused to the baseline (CT1) data using automated mutual-information based
fusion algorithm. Difference between centroids of fiducial markers in various
image modalities was used to assess image registration accuracy. RESULTS: CT/CT
image registration was superior to CT/MR and CT/PET: average CT/CT fusion error
was found to be 0.64 +/- 0.14 mm. Corresponding values for CT/MR and CT/PET
fusion were 1.33 +/- 0.71mm and 1.11 +/- 0.37mm. Internal markers near the center
of phantom fused better than external markers placed on the phantom surface. This
was particularly true for the CT/MR and CT/PET. The inferior quality of external
marker fusion indicates possible distortion effects toward the edges of MR image.
Peripheral targets in the PET scan may be subject to parallax error caused by
depth of interaction of photons in detectors. CONCLUSIONS: Current widespread use
of multimodality imaging in radiotherapy planning calls for periodic quality
assurance of image registration process. Such studies may help improve safety and
accuracy in treatment planning.
PMID- 28519813
TI - SU-E-J-69: Development of an Ambiguity-Free Optical Tracking System for SBRT.
AB - PURPOSE: Commercial optical tracking system such as BrainLab ExacTrac(c) suffers
from ambiguous markers which can cause significant delay in patient treatment. We
developed an ambiguity-free optical tracking system for high precision SBRT.
METHODS: The optical tracking system consists of a pair of camera sensors, 4~8
infra-red (IR) reflective markers affixed on patient skin and in-house developed
software. We developed an effective algorithm to automatically eliminate
ambiguous markers. A recursive backtracking algorithm was developed to build one
to-one correspondence between reference markers and optical markers. The
algorithm was able to deal with missing, misplaced, or occluded markers by
introducing 'dummy' markers. Isocenter displacements were calculated in six
degree of freedom through rigid-body registration between reference markers and
optical markers. The system accuracy was evaluated with a pelvis phantom against
cone beam CT (CBCT) and ExacTrac. The impact of number of markers on tracking
accuracy was also evaluated. The performance of automatic ambiguity elimination
was assessed with synthetic and clinic marker patterns. RESULTS: Difference of
isocenter displacement reported by our system and commercial systems (CBCT,
ExacTrac) were within 0.5 mm/0.1o. Impact of number of markers on tracking
accuracy in our phantom test was negligible with isocenter displacement varying
within 0.2 mm/0.2o when number of markers varied from 4 to 8. The system
successfully identified and eliminated ambiguous markers in both synthetic and
clinic marker patterns. CONCLUSIONS: An accurate optical tracking system free of
ambiguous markers was developed for patient positioning and monitoring in high
precision SBRT. The developed algorithms to eliminate ambiguous markers and to
handle missing, misplaced or occluded markers were effective and efficient.
PMID- 28519815
TI - SU-E-J-80: A Simulation Study with Geant4 on the Yields of Positron-Emitting
Nuclei (10C, 11C, and 15O) Induced by Protons and Carbon Ions.
AB - PURPOSE: To study the yields and the depth-distributions of positron-emitting
nuclei (PEN) 10C, 11C, and 15O induced by protons and carbon ions in PMMA.
METHODS: An application built with various physics packages was constructed with
Geant4 Monte Carlo Toolkit. A phantom of 15 cm * 15 cm * 50 cm consisting of PMMA
(C5H8O2, density 1.18 g/cm3 ) was irradiated with 70, 110 MeV protons and 204 A,
212.12 A MeV carbonions. Beam quality of 1 cm FWHM with 0.2% Gaussian energy
spread FWHM was used. For each beam energy, simulation of the energy deposited
was recorded for every 1 mm increment of depth in the phantom. The resulting PEN
and their yields were recorded at the production point and also at the point of
decay in increments of 1 mm. RESULTS: The overall percentage yields, depth
distributions, and total percentages of PEN per incident particle for both
protons and carbon ions were obtained. Our results found that the predominant
PMMA fragment was 11C irrespective of incident particle type or energy.
CONCLUSIONS: Our yields of PEN are comparable with other simulations (FLUKA and
MCHIT) as well as existing experimental data. The present work however
overestimates the percentage of PEN in the simulations of incident carbon ions
and the percentage of 10C for incident protons compared to the experimental data.
This particular application built within the Geant4 Monte Carlo Toolkit can
estimate the amount of PEN as well as the depth-distributions of these nuclei in
hadron induced radiation therapy.
PMID- 28519814
TI - SU-E-J-108: Quantitative Analysis of Longitudinal Cognitive Impairment Due to
Radiation Therapy Based on Automatic Segmentation of Hippocampus and Subcortical
Structure.
AB - PURPOSE: In this study, we developed a quantitative analysis tool based on
patient's longitudinal MR images to 1) measure the radiation dose received by
each subcortical structure, 2) follow the change of volume and shape of each
structure longitudinally. This tool provides a systematic approach to study the
radiation therapy (and subsequent chemotherapy) associated with cognitive
impairments. METHODS: MRI scans of one patient taken before and after radiation
therapy are demonstrated in this study. 3D Conformal radiation therapy was
performed on RapidArcTM. An open source MRI analysis tool, FMRIB's Integrated
Registration and Segmentation Tool (FIRST), was used for segmentation. The images
are registered to a standard template with expert-defined labeling for all sub
cortical structures, and the labeling of each structure is mapped back to the
individual MRI space for segmentation. After the segmentation, the radiation dose
map was coregistered to the MRI space to calculate the dose received by each
structure. RESULTS: For the structure that is contained within the radiation
zone, we can calculate the total dose based on the volumetric distribution of
radiation dose. For the structure that is outside the radiation field, we can
calculate the distance from the radiation zone. We have demonstrated in this work
that the analysis can be done for all segmented sub-cortical structures. The
change of volume before and after radiation treatment can be analyzed, and the
results can be correlated with the change of cognitive performance over time.
CONCLUSIONS: We presented an automated tool for efficient, quantitative and user
independent measurements of radiation dose in subcortical structures. The
obtained results can be correlated with the cognitive test score and the clinical
outcome to evaluate radiation and the subsequent chemotherapy induced changes in
brain structures and functions.
PMID- 28519816
TI - SU-E-J-90: 2D/3D Registration Using KV-MV Image Pairs for Higher Accuracy Image
Guided Radiotherapy.
AB - PURPOSE: In this work, we investigate the impact of using paired portal mega
voltage (MV) and kilo-voltage (kV) images, on 2D/3D registration accuracy with
the purpose of improving tumor motion tracking during radiotherapy. Tumor motion
tracking is important as motion remains one of the biggest sources of uncertainty
in dose application. 2D/3D registration is successfully used in online tumor
motion tracking, nevertheless, one limitation of this technique is the inability
to resolve movement along the imaging beam axis using only one projection image.
METHODS: Our evaluation consisted in comparing the accuracy of registration using
different 2D image combinations: only one 2D image (1-kV), one kV and one MV
image (1kV-1MV) and two kV images (2-kV). For each of the image combinations we
evaluated the registration results using 250 starting points as initial
displacements from the gold standard. We measured the final mean target
registration error (mTRE) and the success rate for each registration. Each of the
combinations was evaluated using four different merit functions. RESULTS: When
using the MI merit function (a popular choice for this application) the RMS mTRE
drops from 6.4 mm when using only one image to 2.1 mm when using image pairs. The
success rate increases from 62% to 99.6%. A similar trend was observed for all
four merit functions. Typically, the results are slightly better with 2-kV images
than with 1kV-1MV. CONCLUSIONS: We evaluated the impact of using different image
combinations on accuracy of 2D/3D registration for tumor motion monitoring. Our
results show that using a kV-MV image pair, leads to improved results as motion
can be accurately resolved in six degrees of freedom. Given the possibility to
acquire these two images simultaneously, this is not only very workflow efficient
but is also shown to be a good approach to improve registration accuracy.
PMID- 28519817
TI - SU-E-J-101: Weighted Voting Method for Multi-Atlas Segmentation in CT Scans.
AB - PURPOSE: We investigate automating the task of segmenting structures in head and
neck CT scans, to minimize time spent manually contouring. We focus on the
brainstem and left and right parotids. METHODS: To generate contours for an
unlabeled image, we assume an atlas of labeled images. We register each of these
images to the unlabeled target image, transform their structures, and then use a
weighted voting method for label fusion. Our registration method starts with
multi-resolution translational alignment, then applies a relatively higher
resolution affine alignment. We then employ a diffeomorphic demons registration
to deform each atlas to the space of the targetimage. Our weighted voting method
acts one structure at a time to determine for each voxel whether or not it exists
in a structure. The weight for a voxel's vote from each atlas depends on the
intensity difference of the target and the transformed atlas at that voxel, in
addition to the distance of that voxel from the boundary of the structure.
RESULTS: We applied our method to sixteen labeled images, generating automatic
segmentations foreach using the other fifteen images as the atlas. We compared
the resulting Dice and Hausdorff metrics with a majority voting method using the
same registrations and saw remarkable improvement. Mean Dice scores were around
.7, with maximum Hausdorff of about 15mm, and mean Hausdorffs around 2 or 3mm.
CONCLUSIONS: Our method produces contours with boundaries usually only a few
millimeters away from the manual contour, which could save physicians
considerable time, because they only have to make small modifications to each
slice instead of contouring from scratch.
PMID- 28519818
TI - SU-E-J-73: Using Surface-Based Imaging for Patient Identification.
AB - PURPOSE: A feasibility study to determine if daily surface-based imaging can be
used for patient identification with reliable accuracy. METHODS: Three
dimensional surface images were acquired using AlignRT (VisionRT Ltd., London,
UK) prior to daily radiotherapy treatment for 12 breast cancer patients. These
were compared retrospectively to body contours generated from computed tomography
simulation (CT sim) scans. Two types of comparisons were made. The first compared
the surface of each patient for all fractions of treatment. The second compared a
random incorrect patient body contour for each patient in the study. The 'surface
statistic' tool reveals the percentage of surface points within a threshold
distance of 3mm. RESULTS: Comparison of the patients' daily AlignRT images to the
CT sim body contour showed similarity of the surfaces of 81.0% +/- 6.6% with a
total range of 61.5-95.3%. This same comparison of the wrong patient's CT sim
body contour to a random fraction of another patient's AlignRT image revealed
similarity of the surfaces of 27.9% +/- 10.2% with a range of 6.7-58.3%. A
threshold of approximately 60% separates misidentification from correct
identification in our limited study set. There was no overlap between the two
groups in our test. However, we recognize that the two groups come close to the
threshold value and could overlap in a larger study set. CONCLUSIONS: Using daily
surface-based imaging to identify patients is feasible with AlignRT using a
surface statistic threshold of approximately 60%. This has the possibility of
improving radiotherapy safety using existing image-guided technology. Further
study is needed to better understand the sensitivity and specificity of this tool
for a larger patient population.
PMID- 28519819
TI - SU-E-J-112: A Splatting Method to Generate DRRs for Deformed CT Volume.
AB - PURPOSE: To develop an efficient algorithm for generating high-quality digitally
reconstructed radiographs (DRRs) for regularly and irregularly sampled volumes
based on a splatting method with dynamic elliptical Gaussian kernels, and to
evaluate this method using ray tracing. METHODS: The traditional ray tracing
method, which takes every intersected voxel into account, produces high quality
DRRs but is very time consuming. Additionally, it is not suitable for handling
irregularly-sampled volumes since it always requires image re-sampling, which
leads to inaccuracy. We present a splatting approach to compute the 'footprint
function', facilitating efficient perspective projection of elliptical Gaussian
kernels at very low cost. This reported framework allows dealing with both
regularly and irregularly sampled volumes effectively and efficiently. An XCAT
digital phantom was used to generate 3D chest volumes at different respiratory
phases, and CT projections are generated using ray tracing and the splatting
method, respectively. Normalized cross correlation (NCC) is applied to evaluate
the DRR similarity of two methods. RESULTS: Respiratory Phases one and four are
used as volume datasets from the 4D XCAT digital phantom as they represent the
lung at end inhale and end exhale, respectively. The dataset of Phase one is the
basic regularly-sampled volume while the dataset of Phase four is deformed from
that of Phase one, and resampled to a regularly sampled dataset for the ray
tracing method. NCC between splatting and ray tracing DRRs are 0.9980 and 0.9977
for Phase one and Phase four, respectively. The calculation speed of the
splatting method is 3 times faster than that of ray tracing. CONCLUSIONS: Our
splatting approach can generate high-quality DRRs efficiently, and is a good
alternative for current DRR generation techniques for deformed volume datasets.
This research is supported by CPRIT Individual Investigator Award RP110329.
PMID- 28519820
TI - SU-E-J-84: Investigating the Use of Deformable Algorithms to Register and
Accumulate Dose to the Spinal Cord for Head-And-Neck Radiotherapy Patients.
AB - PURPOSE: Mega-voltage cone-beam CT (MVCBCT) imaging can be used to monitor
changes in neck flexion and calculate the true spinal cord dose during
radiotherapy. To sum the dose over multiple fractions and compare with the
planned dose requires deformable image registration. This study investigates the
accuracy of deformable registration of the spine in kilovoltage CT (kVCT) to
MVCBCT images for head-and-neck patients. METHODS: Head-and-neck kVCT and MVCBCT
images were selected from five patients who exhibited large changes in neck
flexion. The spinal canal was contoured in each image. MVCBCT images were rigidly
registered to the kVCT image by aligning the C1-C2 vertebrae. Variations of a
commercial deformable registration algorithm using the B-spline method were
applied to a volume of interest surrounding the spine to deform the spinal cord
structure from the kVCT to the MVCBCT. The Dice similarity index (DSI) was
calculated between rigidly registered structures (DSI1), and compared against the
DSI calculated between the MVCBCT structure and the structure deformed from kVCT
to MVCBCT (DSI2). The difference between DSI2 and DSI1 was calculated to
investigate the ability of the deformation algorithm to match the change in neck
flexion. RESULTS: In this data set, a single-pass B-spline deformation algorithm
was the most effective in deforming the kVCT spinal canal to the MVCBCT spinal
canal, with a mean improvement in DSI (DSI2 - DSI1) of 0.134. The mean change in
DSI for a single-pass algorithm with a contrast correction was 0.111; for a
multiple-pass algorithm was 0.105; and for a multiple-pass algorithm with
contrast correction was 0.075. CONCLUSIONS: Several versions of a commercially
implemented B-spline deformation algorithm were found to improve the registration
of the spinal canal in kVCT and MVCBCT head-and-neck images. The resulting
accuracy in the calculation of the cumulative dose to the spinal cord is under
investigation. We acknowledge Velocity for providing the registration software.
PMID- 28519821
TI - SU-E-J-75: Practical Annual Quality Assurance Program for a Real Time Optical
Tracking System.
AB - PURPOSE: To verify the accuracy of a real time optical surface tracking system
using a practical annual quality assurance program with an anthropomorphic breast
phantom. METHODS: An anthropomorphic breast phantom was used to determine the
accuracy of registration, shift, source to surface distance (SSD), and live
monitoring features of the AlignRT system. Both the two and three camera AlignRT
systems were tested. Registration and shift accuracy were evaluated by comparing
software output with known phantom displacements and rotations at 0, 90, and 270
couch angles. These tests were performed in static capture and live monitoring
modes. SSD accuracy was determined by comparing AlignRT results with expected
values from the treatment planning system and optical distance indicator at 0,
90, and 270 degree couch rotations. RESULTS: For the two camera system,
registration accuracy at 0, 90, and 270 degree couch angles was within 1.0mm in
the lateral, longitudinal, and vertical directions and 0.04 degree. For shifts of
+/-10mm and +/-5 degree, static mode shift accuracy was within 1.6mm and 0.23
degree. Registration accuracy of the shifted phantom in live monitoring mode was
within 1.7mm and 0.2 degree. For the three camera system, registration accuracy
at 0, 90, and 270 degree couch angles was within 1.1 mm in the lateral,
longitudinal, and vertical directions and 0.2 degree. For shifts of +/-10mm and
+/-5 degree, static mode shift accuracy was within 0.9mm and 0.2 degree.
Registration accuracy of the shifted phantom in live monitoring mode was within
1.1mm and 0.2 degree. SSD determination was accurate to within 2mm for both
systems and modes. CONCLUSIONS: The AlignRT system accuracy can be easily
verified for annual quality assurance using a realistic clinical setup to within
2mm/0.5 degree. System accuracy was comparable for both two and three camera
systems in static and live monitoring modes.
PMID- 28519822
TI - SU-E-J-114: Web-Browser Medical Physics Applications Using HTML5 and Javascript.
AB - PURPOSE: Since 2010, there has been a great attention about HTML5. Application
developers and browser makers fully embrace and support the web of the future.
Consumers have started to embrace HTML5, especially as more users understand the
benefits and potential that HTML5 can mean for the future.Modern browsers such as
Firefox, Google Chrome, and Safari are offering better and more robust support
for HTML5, CSS3, and JavaScript. The idea is to introduce the HTML5 to medical
physics community for open source software developments. The benefit of using
HTML5 is developing portable software systems. METHODS: The HTML5, CSS, and
JavaScript programming languages were used to develop several applications for
Quality Assurance in radiation therapy. The canvas element of HTML5 was used for
handling and displaying the images, and JavaScript was used to manipulate the
data. Sample application were developed to: 1. analyze the flatness and symmetry
of the radiotherapy fields in a web browser, 2.analyze the Dynalog files from
Varian machines, 3. visualize the animated Dynamic MLC files, 4. Simulation via
Monte Carlo, and 5. interactive image manipulation. RESULTS: The programs showed
great performance and speed in uploading the data and displaying the results. The
flatness and symmetry program and Dynalog file analyzer ran in a fraction of
second. The reason behind this performance is using JavaScript language which is
a lower level programming language in comparison to the most of the scientific
programming packages such as Matlab. The second reason is that JavaScript runs
locally on client side computers not on the web-servers. CONCLUSIONS: HTML5 and
JavaScript can be used to develop useful applications that can be run online or
offline on different modern web-browsers. The programming platform can be also
one of the modern web-browsers which are mostly open source (such as Firefox).
PMID- 28519823
TI - SU-E-J-86: Free form Deformable Model Based on Multi-Resolution B-Spline Grid for
Registration of 4D CT Images of Hepatocellular Carcinoma Patients.
AB - PURPOSE: The breathing motion has a significant influence to radiation therapy of
hepatocellular carcinoma patients, and the motions are irregular. We used
deformable registration of four-dimensional computed tomography (4D CT) data to
eliminate breathing motion artifact to truly track the tumors' positions and
shapes, and guide medical physicists to delineate the more accurate tumor targets
for treatment planning. METHODS: We collected 4D CT data of 8 hepatocellular
carcinoma patients, 4D-CT images were segmented into 10 serious CT images
according the respiratory phase, and named CT0,CT10'|CT90, and CT0 was at end
inspiration, CT50 was at end expiration. We proposed the free form deformable
(FFD) model based on multi-resolution B-spline grid registration method to the 4D
CT data during a whole breathing cycle, and we used L-BFGS to optimize system and
multi-resolution to pick up the registration speed and accuracy. In particular we
defined the gross target volume of HCC with the help of iodipin on CT images
which can verify the registration performance. We chose end-exhale CT as the
reference image. RESULTS: We compared the floating images, the subtractions of
floating images and reference image, the iodipin landmarks' positions and the
multi-informations between floatings image and reference image before and after
registered to verify the registration performance. From the registered images, we
can track the 'trajectory' of the tumors during a whole breathing cycle, and the
average multi-information improved 3.5% after registration between the two
extreme phases. CONCLUSIONS: Wecan use this registration method to register the
4D CT data and use iodipin on CT images to define gross target volume to guide
medical physicists delineating the more accurate tumor targets.
PMID- 28519824
TI - SU-E-J-96: Investigation into the Accuracy of Deformable Registration Algorithms
for Use in Dose Summation: A Case Study in Combined Modalities.
AB - PURPOSE: To better understand the accuracy and limitation of deformable
registration algorithms for dose summation by studying the results produced
through two different deformable registration techniques for a clinical case of
combining a Cyberknife radiosurgery plan and an electron boost to the scar
tissues. METHODS: A patient was treated with a Cyberknife plan with supine CT and
an electron boost plan with prone CT concurrently. The CT, RT structures and dose
grids were exported from the Cyberknife MultiPlan system and the Pinnacle system
and imported into two commercial DICOM viewing systems equipped with deformable
registration algorithms. One of the systems uses intensity-based free-form
deformable registration while the other uses B-spline free-form deformable
registration. The electron boost plan was first registered to the CK plan using
rigid registration, then secondly using deformable registration in each system.
The region of interest used for registration was chosen to encompass the whole CT
volumes due to the supine vs. prone positions. RESULTS: The summation doses for
the Cyberknife CTV and critical structures do not differ between rigid
registration and deformable registration for both systems. The electron boost
volume does show higher mean dose received for the deformable registration
compared with rigid registration for both systems (12.90 Gy vs. 11.71 Gy and
12.39 Gy vs. 11.53 Gy). There are slight variations between the doses produced by
the two systems for all the structures, with an averaged difference of
approximately 0.02% to 2.63%. CONCLUSIONS: These results show that for cases like
this one, where the two treatment volumes do not overlap, there will not be
significant differences between rigid and deformable registration, and that the
only significant difference in summation dose between the different deformable
registration algorithms is where the volume is deformed the most, in this case,
the electron boost volume.
PMID- 28519825
TI - SU-E-J-68: An Optical Image Guidance System: To Detect Arbitrarily Attached
Markers Behind a Full Facemask.
AB - PURPOSE: We developed an optical image guidance system to manage patient's inter
fractional set-up errors by tracking external markers at the specific positions
(e.g., nose tip) behind a full facemask. However, a problem associated with the
reproducibility of the marker positions during the entire course of treatments
still remains. In order to remove this disadvantage, we applied the arbitrary
point-to-plane registration method to our existing system. METHODS: Infra-red
(IR) reflecting markers were attached on arbitrary positions of the head
phantom's face and then the phantom was immobilized by a full face thermoplastic
mask. 3D coordinates of the IR markers behind the full facemask were
reconstructed by the calibrated stereo camera system using the direct linear
transform (DLT) algorithm. In order to match arbitrarily attached markers with a
planning CT image, rough positions of three markers were manually defined (rough
registration) and then the coordinates of all markers were determined through the
point-to-plane registration using the contractive projection point (CPP)
algorithm (fine registration). In addition, the marker registration error in 6
DOF was calculated. In order to validate accuracy of the system, the phantom was
intentionally moved according to 10 sets of known translation parameters.
RESULTS: A mean target registration error (TRE) determined by the experiments for
arbitrarily attached markers was 1.24 +/- 0.32 mm. The fine registration
following the rough registration allowed fast and robust registrations.
CONCLUSIONS: The proposed solution for arbitrarily attached markers behind a full
facemask enables us to avoid any daily errors in attaching the external markers
at the specific positions. This work was supported in part by the SNU
interdisciplinary project (2009-2010) and the SNU Brain Fusion project (2010
2011).
PMID- 28519826
TI - SU-E-J-107: Feasibility of Complete Brain Simulation Using Single MRI
Acquisition.
AB - PURPOSE: To evaluate the information available from a single MRI acquisition for
a complete MRI-based simulation in brain. METHOD AND MATERIALS: A 3.0T MRI
scanner (Achieva TX, Philips Healthcare) was used to acquire a complete brain
simulation data set in a single acquisition on four consenting volunteers. The
acquisition consisted of collecting the FID signal (TE1 = 100MUs) followed by two
additional gradient echoes (TE2/TE3= 1.4ms/2.5ms) using a 3D volumetric
excitation and radial read-out toachieve 1.3mm isotropic voxels. The data from
this single acquisition was used to reconstruct five volumetric data sets: Bone
enhanced, fat-only, water-only, in-phase and out-of-phase. The resulting image
sets were assessed for image quality sufficient for organ delineation and used to
generate digitally-reconstructed radiographs (DRRs) (Pinnacle Workstation,
Philips Healthcare). RESULTS: Each volunteer study took less than 10 minutes to
complete, and the single acquisition required less than 3 minutes. Images from
all four volunteers had excellent image quality sufficient for organ delineation
and complete cortical bone segmentation. In addition, the DDRs for all four
volunteers were sufficient for 2D patient matching. CONCLUSION: This study
confirms the feasibility of using a single acquisition MRI as a sole imaging
modality for treatment planning simulation in the brain. To validate this method,
we plan to use this imaging protocol in a group of patients and compare the DRRs
and dose plans with those acquired during CT simulation. Both authors are
employees of Philips Healthcare.
PMID- 28519827
TI - SU-E-J-79: Using the Distance of Closest Approach to Improve Compton Camera Image
Quality.
AB - PURPOSE: The prompt gamma radiation emitted from tissue during proton therapy
offers a means of beam range verification. Compton camera (CC) imaging systems
offer high efficiency and 3D imaging capability. However, Doppler broadening and
the inaccuracies in the measurement of the scattering positions and energies
reduce the image resolution. The purpose of our study is to determine if removing
events with a distance-of-closest-approach greater than a threshold value will
improve the resolution of images reconstructed using the stochastic origins
ensemble (SOE) algorithm. METHODS: We first simulated a 3-stage CC detecting
gammas from a 0.511 MeV point source. We then used SOE to reconstruct images from
the point source and from a) all gammas, b) gammas with DCA < 3 mm, and c) gammas
with DCA < 1 mm. We measured the point-spread-function for the point source for
a), b), and c). Next, we simulated a 3-stage CC detecting prompt gammas emitted
from tissue during proton therapy. We reconstructed the gammas using SOE and
compared 2D images of all gammas, gammas with DCA < 3 mm, and gammas with DCA < 1
mm. RESULTS: The FWHM of the PSF of the 0.511 MeV point source was reduced by 50%
when DCA was required to be < 5 mm, and it was reduced by 65% when DCA was
required to be < 3 mm. 2D images of a proton beam are of visibly higher quality
as the DCA requirement is lowered. CONCLUSIONS: The DCA for MC events can be used
to identify the events with significant resolution loss due to the detector
effects. Removing these events before running the reconstruction algorithm
results in higher quality images. We discuss methods to predict the DCA based on
the measured scatter data, so that a similar technique can be applied to data
from real detectors. This work was supported by the National Institutes of Health
through award number R21CA137362 from the National Cancer Institute.
PMID- 28519828
TI - SU-E-J-119: Comparative Evaluation of Respiratory Motion-Corrected Cone-Beam CT
Images Derived from Treatment-Day Vs. Simulation-Day Respiration-Correlated CT
Scans.
AB - PURPOSE: Respiration-induced motion artifacts in cone-beam CT (CBCT) can be
corrected using a model of patient motion obtained from respiration-correlated CT
(RCCT). This approach assumes that respiration-induced organ deformations at
simulation, when RCCT scans are normally acquired, are still valid at treatment.
The purpose of this study is to compare lung tumor image quality in motion
corrected CBCT images derived from treatment-day RCCT(tx) to simulation-day
RCCT(sim) patient images. METHODS: In an IRB-approved study, lung cancer patients
receive an RCCT at simulation, and an RCCT, gated CBCT and 1-minute CBCT at one
treatment session. CBCT projections from the 1-minute scan are sorted according
to breathing amplitude from an external monitor and reconstructed and warped to
obtain a motion-corrected MC-CBCT at end expiration. Motion correction uses a
model adapted from either RCCT(tx) or RCCT(sim), thus obtaining MC-CBCT(tx) and
MC-CBCT(sim) images respectively. A gated CBCT, in which gantry rotation and
projection acquisition occur within a gate at end expiration, serves as ground
truth for comparison. Quality of MC-CBCT images is evaluated from tumor-to
background contrast ratio (TBCR) values measured by delineating the tumor and
annular volume around it on the gated CBCT then transferring the contours and
aligning them to each MC-CBCT. RESULTS: TBCR is found tobe lower in MC-CBCT(sim)
images, relative to MC-CBCT(tx), in four out of five patients with mean 21%
reduction in a range 9-39%. In the remaining case, where there was no change in
TBCR, tumor motion observed in the RCCT was small (2mm). Tumor motion extent
relative to diaphragm is observed to change between RCCT(tx) and RCCT(sim) scans.
CONCLUSIONS: Preliminary results indicate that deformation patterns in lung do
change between simulation and treatment. Such variations may reduce the validity
of using simulation data for motion-corrected CBCT at treatment. The findings
require confirmation with larger numbers of patients. NIH/NCI award R01 CA126993,
research grant from Varian Medical Systems.
PMID- 28519829
TI - SU-E-J-89: Deformable Registration Method Using B-TPS in Radiotherapy.
AB - PURPOSE: A novel deformable registration method for four-dimensional computed
tomography (4DCT) images is developed in radiation therapy. METHODS: The proposed
method combines the thin plate spline (TPS) and B-spline together to achieve high
accuracy and high efficiency. The method consists of two steps. First, TPS is
used as a global registration method to deform large unfit regions in the moving
image to match counterpart in the reference image. Then B-spline is used for
local registration, the previous deformed moving image is further deformed to
match the reference image more accurately. RESULTS: Two clinical CT image sets,
including one pair of lung and one pair of liver, are simulated using the
proposed algorithm, which results in a tremendous improvement in both run-time
and registration quality, compared with the conventional methods solely using
either TPS or B-spline. CONCLUSIONS: The proposed method can combine the
efficiency of TPS and the accuracy of B-spline, performing good adaptively and
robust in registration of clinical 4DCT image.
PMID- 28519830
TI - SU-E-J-100: Feasibility of Dose Calculation Using Combined Information of Cone
Beam and Multi-Slice CT Images.
AB - PURPOSE: The purpose of this study is to evaluate the feasibility of kilovoltage
cone-beam CT (CBCT) images that are obtained with the Varian On-Board Imager in
dose calculation at each radiation therapy. METHODS: CBCT images are commonly
degraded by scattered radiations originating in the patient's body, and so the CT
numbers of the CBCT images depend on data acquisition conditions and the patient
size. However, the anatomical shape of each organ is not likely affected by
scattered radiations, and so we used only the shape of major organs such as lungs
and bones in the CBCT images, and replaced these CT numbers with those of the
multi-slice CT (MSCT) images that were used for dose calculation in a treatment
planning. As regards this alternative CT number we adopted the median of MSCT
numbers in a segmented region of a major organ each corresponding to that in the
CBCT images. We evaluated the validity of our segmented region (SR) method with
images of eight patients with lung diseases. The number of irradiation beams was
four. In this evaluation we used the distance-to-agreement (DTA) and y analysis,
and the dose-volume-histogram (DVH) analysis. RESULTS: The pass rates of the DTA
analysis (2mm) and gamma analysis (2mm, 2%) between the dose distributions
calculated with our method were 90.4+/-6.0% and 99.1+/-1.1%, respectively. The
results of the DVH analysis showed that the differences in doses (average,
maximum and minimum) for a target volume were 1.3+/-0.5%, 0.9+/-0.8% and 3.4+/
3.0%, respectively. These results showed that our method was acceptable in the
calculation of a dose distribution. CONCLUSION: We evaluated the dose calculation
method with a combination of CBCT and MSCT images. This method could yield an
accurate dose distribution and achieved an easier verification of radiation
therapy on each treatment day.
PMID- 28519831
TI - SU-E-J-72: Design and Study of In-House Web-Camera Based Automatic Continuous
Patient Movement Monitoring and Controlling Device for EXRT.
AB - PURPOSE: The purpose of our study was to fabricate in-house web-camera based
automatic continuous patient movement monitoring device and control the movement
of the patients during EXRT. METHODS: Web-camera based patient movement
monitoring device consists of a computer, digital web-camera, mounting system,
breaker circuit, speaker, and visual indicator. The computer is used to control
and analyze the patient movement using indigenously developed software. The
speaker and the visual indicator are placed in the console room to indicate the
positional displacement of the patient. RESULTS: Studies were conducted on
phantom and 150 patients with different types of cancers. Our preliminary
clinical results indicate that our device is highly reliable and can accurately
report smaller movements of the patients in all directions. The results
demonstrated that the device was able to detect patient's movements with the
sensitivity of about 1 mm. When a patient moves, the receiver activates the
circuit; an audible warning sound will be produced in the console. Through real
time measurements, an audible alarm can alert the radiation technologist to stop
the treatment if the user defined positional threshold is violated.
Simultaneously, the electrical circuit to the teletherapy machine will be
activated and radiation will be halted. CONCLUSIONS: Patient's movement during
the course for radiotherapy was studied. The beam is halted automatically when
the threshold level of the system is exceeded. By using the threshold provided in
the system, it is possible to monitor the patient continuously with certain fixed
limits. An additional benefit is that it has reduced the tension and stress of a
treatment team associated with treating patients who are not immobilized. It also
enables the technologists to do their work more efficiently, because they don't
have to continuously monitor patients with as much scrutiny as was required.
PMID- 28519832
TI - SU-E-J-111: Compute the Optimal Threshold for PET Functional Volume Delineation.
AB - PURPOSE: To construct a method being able to compute the optimal threshold (OT)
directly from PET images for functional volume delineation without any a priori
information about scanners, imaging protocols and tumor size. METHODS: A
mathematic model for partial volume effect (PVE) was analyzed for a spherical
object with a constant activity imaged by a scanner with Gaussian point spread
function (PSF). The theoretic analysis showed that information about some factors
that are related to the PVE such as the PSF and tumor size had been actually
embedded into PET images. We developed a new concept - the Optimal Area Ratio
(OAR) that is a function of the object radius and can be derived from the model
with some mathematic manipulations. With this new concept, information about PSF
and tumor size can be recovered directly from PET images, and the OT can be
calculated accordingly. The basic idea is to use the whole dynamic behavior (the
behavior of the volume sizes due to different thresholds uniformly distributed in
[0,1]) of a region-growing algorithm to find the OT. A computer simulation and
experiments on phantoms with different object sizes and different noise levels
were conducted to evaluate the above theoretic analysis. RESULTS: For the
computer simulation, the calculated OT was exactly the real OT. In the
experiments on phantoms, the calculated OT led to visually satisfactory
delineation results. CONCLUSIONS: The new theoretic analysis showed that the OT
can be calculated without any a priori information about scanners, imaging
protocols and tumor size. The computer simulation and phantom experiments
validated the theoretic analysis.
PMID- 28519833
TI - SU-E-J-83: Improving Respiration-Gated IMRT Delivery Efficiency by Dual-Gating at
Inhale and Exhale: Evaluation of Planning on Eclipse and the Need for Accurate
Image Registration.
AB - PURPOSE: Dual-gated intensity modulated radiation therapy (DG-IMRT) is a novel
delivery method for speeding respiratory-gated IMRT delivery in which dose is
delivered during both inhale and exhale windows. To determine the feasibility of
designing DG-IMRT plans using current clinical treatment planning systems, we
design and evaluate a lung patient plan using Eclipse. METHODS: Tumor target
volumes were contoured on inhale and exhale CTs for a lung cancer patient with
~1mm motion. Separate 5-field IMRT plans were optimized in Eclipse for the inhale
PTV on the inhale CT and for the exhale PTV on the exhale CT. The inhale plan
dose was mapped to the exhale geometry using several deformable medical image
registration methods, and the two doses were summed to produce the DG-IMRT dose.
The accumulated dual-gated dose for the best performing registration is
presented. RESULTS: Though the dual-gated inhale and exhale plans meet clinical
requirements, the accumulated dual-gated dose performs quite poorly. Examination
of the deformations indicates that only about two-thirds of the voxels within the
inhale PTV map to voxels within the exhale PTV, indicating an unacceptably low
level of physiological accuracy. CONCLUSION: It is possible to design dual-gated
plans in Eclipse, but there is currently no accurate means of evaluated the
summed dose. Furthermore, our results underscore the need for image registration
methods that accurately model underlying tissue deformations before they can be
used for dose accumulation in the presence of organ motion. This work was
supported by the National Cancer Institute (T32 CA09695 - Glazer) and the
National Institutes of Health (1RO1 CA 133474 - Xing).
PMID- 28519834
TI - SU-E-J-93: Fourier Transform-Based Medical Image Registration.
AB - PURPOSE: To evaluate the use of a Fast Fourier Transform (FFT) based pattern
matching algorithm for two-dimensional translational and rotational medical image
registration. METHODS: The FFT pattern matching algorithm is based on the Fourier
shift theorem. Briefly, image registration is accomplished by obtaining the
Fourier Transform (FT) of two images, taking the normalized cross-correlation of
the two FT, and performing an inverse FT on this correlation matrix. This results
in a Dirchlet delta function that has a maximum value at a location corresponding
to the translational shift between the two images. Rotational registration can
also be achieved by performing this algorithm on the polar transformation of the
FT images. The FT registration method was evaluated through the use of clinical
images with induced translational and rotational shifts. RESULTS: Over a range of
induced shifts of +/-10 mm in both the x and y directions, and induced rotations
of +/-10 degrees, all recovered rotations were within 0.1 degree of the induced
rotation, and all recovered translations were within 0.5 mm of the induced
translation. The computational time of the FT registration on a 1024*1024 image
was approximately 2.23 sec. CONCLUSIONS: An FFT based image registration
algorithm is computationally efficient and provides a high degree of accuracy for
two dimensional image registrations. The FFT registration approach provides a
distinct analytical solution and does not rely on iterative methods to converge
on a solution. In addition, the discrete nature of the FFT means that the
accuracy of the solution is directly related to the size of the pixels in the
images. The equivalent of sub-pixel registration can be achieved by simply
resizing the image to a larger matrix (i.e. 512*512 to 1024*1024).
PMID- 28519896
TI - Sixtieth Annual Meeting of the Canadian Organization of Medical Physicists and
the Canadian College of Physicists in Medicine.
PMID- 28519835
TI - SU-E-J-64: Towards a Patient Specific Deformation Model in the Male Pelvis for
IGRT via Limited Angle Imaging.
AB - PURPOSE: To evaluate the feasibility of patient specific deformation models
(PSDM) in the male pelvis for IGRT by limited angular imaging. METHODS: In IGRT
via limited angular imaging, insufficient angular projections are acquired to
uniquely determine a 3D attenuation distribution. For highly limited geometries,
image quality may be too poor for successful non-rigid registration. This can be
overcome by restricting the transformation space to one containing only feasible
transformations learned from prior 3D images. This has been successfully applied
in the lung region where a majority of deformation is due to respiratory motion
which can be adequately observed at planning time with RCCT. Typically, the
phases of the RCCT are registered together to form an group-wise mean image and
transformations to each training image. PCA is then performed on the
transformation displacement vector fields. The transformation is found at
treatment time by registration of digitally reconstructed radiographs of the
transformed image to the measured projections, optimizing over the parameters of
the PCA subspace. In the male pelvis, deformation is much more complicated than
respiratory deformation and is largely inter-fractional due to changes in bladder
and rectal contents, articulation, and motion of the bowels. A similar model is
developed for the male pelvis which takes into account pelvic anatomical
information and handles the more complicated deformation space. RESULTS: Using
the leave-one-out method, dice similarity coefficients in the prostate compared
with manual segmentations are increased over the those obtained by rigid
registration and are comparable with those obtained by 3D non-rigid registration
methods. CONCLUSIONS: This method produces better results than rigid registration
and is comparable with results obtained by 3D/3D registration even though it uses
limited angle projections. However, its relies on daily training CTs, so it is
not yet a viable clinical method. Funding provided in part by Siemens Medical.
PMID- 28519898
TI - Evaluating the effect of a year-long film focused environmental education program
on Ugandan student knowledge of and attitudes toward great apes.
AB - Films, as part of a larger environmental education program, have the potential to
influence the knowledge and attitudes of viewers. However, to date, no
evaluations have been published reporting the effectiveness of films, when used
within primate range countries as part of a conservation themed program. The
Great Ape Education Project was a year-long environmental education program
implemented in Uganda for primary school students living adjacent to Kibale
National Park (KNP) and Bwindi Impenetrable National Park (BINP). Students viewed
a trilogy of conservation films about great apes, produced specifically for this
audience, and participated in complementary extra-curricular activities. The
knowledge and attitudes of students participating in the program from KNP, but
not BINP were assessed using questionnaires prior to (N = 1271) and following (N
= 872) the completion of the program. Following the program, students
demonstrated a significant increase in their knowledge of threats to great apes
and an increase in their knowledge of ways that villagers and students can help
conserve great apes. Additionally, student attitudes toward great apes improved
following the program. For example, students showed an increase in agreement with
liking great apes and viewing them as important to the environment. These data
provide evidence that conservation films made specifically to address regional
threats and using local actors and settings can positively influence knowledge of
and attitudes toward great apes among students living in a primate range country.
PMID- 28519899
TI - Hepatic AA amyloidosis in a cat: cytologic and histologic identification of AA
amyloid in macrophages.
AB - A 3-year-old, spayed female, Domestic Shorthair cat presented with anorexia,
lethargy, vomiting, probable hemoabdomen, and multiple masses on the right
lateral liver lobe. Clinicopathologic and imaging abnormalities included anemia,
azotemia, icterus, and hepatomegaly with hypoechoic masses. On cytologic
evaluation of a fine-needle aspiration of a liver mass there was abundant
extracellular pink- to purple-colored material between hepatocytes. The amorphous
material was stained with direct fast scarlet (DFS), and green birefringent areas
were observed under polarized light, confirming the presence of amyloid. A unique
finding on the cytologic smear were macrophages containing amorphous and
fibrillar amyloid-like protein. Histopathologic examination using H&E and Congo
red staining confirmed amyloid deposits within the space of Disse, along the
sinusoids, portal tracts, blood vessel walls, and within the cytoplasm of
macrophages. Immunohistochemical staining with anti-AA amyloid antibodies further
confirmed the presence of AA amyloid. To the author's knowledge, this is the
first report of the cytologic finding of AA amyloid protein within macrophages
and DFS stain detection of amyloid on a cytologic smear.
PMID- 28519900
TI - Type I interferon pathway in CNS homeostasis and neurological disorders.
AB - Type I interferons (IFNs), IFN-alpha and IFN-beta, represent the major effector
cytokines of the host immune response against viruses and other intracellular
pathogens. These cytokines are produced via activation of numerous pattern
recognition receptors, including the Toll-like receptor signaling network,
retinoic acid-inducible gene-1 (RIG-1), melanoma differentiation-associated
protein-5 (MDA-5) and interferon gamma-inducible protein-16 (IFI-16). Whilst the
contribution of type I IFNs to peripheral immunity is well documented, they can
also be produced by almost every cell in the central nervous system (CNS).
Furthermore, IFNs can reach the CNS from the periphery to modulate the function
of not only microglia and astrocytes, but also neurons and oligodendrocytes, with
major consequences for cognition and behavior. Given the pleiotropic nature of
type I IFNs, it is critical to determine their exact cellular impact.
Inappropriate upregulation of type I IFN signaling and interferon-stimulated gene
expression have been linked to several CNS diseases termed "interferonopathies"
including Aicardi-Goutieres syndrome and ubiquitin specific peptidase 18 (USP18)
deficiency. In contrast, in the CNS of mice with virus-induced neuroinflammation,
type I IFNs can limit production of other cytokines to prevent potential damage
associated with chronic cytokine expression. This capacity of type I IFNs could
also explain the therapeutic benefits of exogenous type I IFN in chronic CNS
autoimmune diseases such as multiple sclerosis. In this review we will highlight
the importance of a well-balanced level of type I IFNs for healthy brain
physiology, and to what extent dysregulation of this cytokine system can result
in brain 'interferonopathies'.
PMID- 28519901
TI - Inhibition of soil microbial activity by nitrogen-based energetic materials.
AB - We investigated individual toxicities of the nitrogen-based energetic materials
(EMs) 2,4-dinitrotoluene (2,4-DNT); 2-amino-4,6-dinitrotoluene (2-ADNT); 4-amino
2,6-dinitrotoluene (4-ADNT); and nitroglycerin (NG) on microbial activity in
Sassafras sandy loam (SSL) soil, which has physicochemical characteristics that
support very high qualitative relative bioavailability for organic chemicals.
Batches of SSL soil for basal respiration (BR) and substrate-induced respiration
(SIR) assays were separately amended with individual EMs or acetone carrier
control. Total microbial biomass carbon (biomass C) was determined from CO2
production increases after addition of 2500 mg/kg of glucose-water slurry to the
soil. Exposure concentrations of each EM in soil were determined using US
Environmental Protection Agency method 8330A. Basal respiration was the most
sensitive endpoint for assessing the effects of nitroaromatic EMs on microbial
activity in SSL, whereas SIR and biomass C were more sensitive endpoints for
assessing the effects of NG in soil. The orders of toxicity (from greatest to
least) were 4-ADNT > 2,4-DNT = 2-ADNT > NG for BR; but for SIR and biomass C, the
order of toxicity was NG > 2,4-DNT > 2-ADNT = 4-ADNT. No inhibition of SIR was
found up to and including the greatest concentration of each ADNT tested in SSL.
These ecotoxicological data will be helpful in identifying concentrations of
contaminant EMs in soil that present acceptable ecological risks for biologically
mediated processes in soil. Environ Toxicol Chem 2017;36:2981-2990. Published
2017 Wiley Periodicals Inc. on behalf of SETAC.This article is a US government
work and, as such, is in the public domain in the United States of America.
PMID- 28519903
TI - Functional neuroimaging offers insights into delirium pathophysiology: A
systematic review.
AB - OBJECTIVE: This systematic review describes the current functional neuroimaging
literature in delirium, discusses pathophysiological implications of these
results and highlights areas for further study. METHODS: In accordance with
Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, an
extensive search of medical databases was undertaken, identifying eighteen
studies of variable quality and design suitable for inclusion. RESULTS:
Functional neuroimaging has highlighted significant abnormalities during
delirium, with disturbances in cerebral haemodynamics and functional connectivity
potentially playing a key role in delirium pathophysiology. CONCLUSIONS: Although
employing functional neuroimaging in delirium remains difficult, these findings
demonstrate the potential of functional imaging to increase our understanding of
the underlying mechanisms of delirium, to lead to more efficient interventions
and targeted therapies and to reduce the burden of this underdiagnosed syndrome.
PMID- 28519963
TI - Shift in paradigm of clinical management of anastomotic leak?
PMID- 28519902
TI - Reduced gliotransmitter release from astrocytes mediates tau-induced synaptic
dysfunction in cultured hippocampal neurons.
AB - Tau is a microtubule-associated protein exerting several physiological functions
in neurons. In Alzheimer's disease (AD) misfolded tau accumulates intraneuronally
and leads to axonal degeneration. However, tau has also been found in the
extracellular medium. Recent studies indicated that extracellular tau uploaded
from neurons causes synaptic dysfunction and contributes to tau pathology
propagation. Here we report novel evidence that extracellular tau oligomers are
abundantly and rapidly accumulated in astrocytes where they disrupt intracellular
Ca2+ signaling and Ca2+ -dependent release of gliotransmitters, especially ATP.
Consequently, synaptic vesicle release, the expression of pre- and postsynaptic
proteins, and mEPSC frequency and amplitude were reduced in neighboring neurons.
Notably, we found that tau uploading from astrocytes required the amyloid
precursor protein, APP. Collectively, our findings suggests that astrocytes play
a critical role in the synaptotoxic effects of tau via reduced gliotransmitter
availability, and that astrocytes are major determinants of tau pathology in AD.
PMID- 28519965
TI - Micellar electrokinetic chromatography fingerprinting combined with chemometrics
as an efficient strategy for evaluating the quality consistency and predicting
the antioxidant activity of Lianqiao Baidu pills.
AB - An approach combining micellar electrokinetic chromatography fingerprinting with
chemometrics was developed to evaluate the quality consistency of Lianqiao Baidu
pills, which are traditional Chinese patent medicines composed of 19 herbs used
mainly to treat skin ulcers, common cold, rheumatism, herpes, and constipation.
The triangle optimization method was employed to choose a satisfactory background
electrolyte, with the information index, I, as an objective function for
assessing the capillary electrophoresis conditions. Then, under the optimal
conditions, the micellar electrokinetic chromatography fingerprints of 28 batches
of samples were established, and five marker compounds were quantitatively
determined simultaneously. A limited-ratio quantified fingerprint method was
introduced to evaluate the chromatographic fingerprints both qualitatively and
quantitatively. Principle component analysis revealed that the 28 batches of
samples can be clustered according to different manufacturers. Moreover, the
relationship between the fingerprint and the antioxidant activity was explored by
orthogonal partial least-squares regression, which provided critical medicinal
efficacy information for quality control. The present study establishes a
powerful and reliable method for monitoring the quality consistency of Lianqiao
Baidu pill.
PMID- 28519967
TI - WE-D-218-01: Ultrasound Scanner Innovations and Clinical Practice.
AB - : Of all the imaging modalities, ultrasound scanners have gone through the most
profound changes over the last several decades in terms of their size,
capability, and cost. Much of this is due to the small data acquisition devices
(ultrasound transducers) and Moore's Law dependent signal/image processors that
comprise and ultrasound scanner. These are in direct contrast with the front ends
of MRI or CT scanners with their sizeable power hungry gantries. Thus ultrasound
has been a direct beneficiary of the miniaturization associated with the
semiconductor industry; this has enabled the migration of much hardware
functionality to software and development of much smaller devices even including
handheld scanners. Such changes are having a significant impact on clinical
utilization of ultrasound. This talk will review some of these including the
recent introduction of complete software backends, i.e. ultrasound scanners
composed of analog front ends which are connected to processors with minimal
dedicated digital hardware. LEARNING OBJECTIVES: 1. Understand the architecture
of an ultrasound scanner and how it has changed with evolving technology. 2.
Understand the implications to clinical practice from these changes. 3.
Understand the possibilities for the future of ultrasound scanners both from the
view of new technical capabilities and how these might impact the clinic.
PMID- 28519964
TI - Association between serum 25-hydroxyvitamin D and glycated hemoglobin levels in
type 2 diabetes patients with chronic kidney disease.
AB - AIMS/INTRODUCTION: Vitamin D is suggested to influence glucose homeostasis. An
inverse relationship between serum 25-hydroxyvitamin D (25[OH]D) and glycemic
control in non-chronic kidney disease (CKD) patients with type 2 diabetes was
reported. We aimed to examine this association among type 2 diabetes patients
with CKD. MATERIALS AND METHODS: A total of 100 type 2 diabetes participants with
stage 3-4 CKD were recruited. Blood for glycated hemoglobin (HbA1c ), serum
25(OH)D, renal and lipid profiles were drawn at enrollment. Correlation and
regression analyses were carried out to assess the relationship of serum 25(OH)D,
HbA1c and other metabolic traits. RESULTS: A total of 30, 42, and 28% of
participants were in CKD stage 3a, 3b and 4, respectively. The proportions of
participants based on ethnicity were 51% Malay, 24% Chinese and 25% Indian. The
mean (+/-SD) age and body mass index were 60.5 +/- 9.0 years and 28.3 +/- 5.9
kg/m2 , whereas mean HbA1c and serum 25(OH)D were 7.9 +/- 1.6% and 37.1 +/- 22.2
nmol/L. HbA1c was negatively correlated with serum 25(OH)D (rs = -0.314, P =
0.002), but positively correlated with body mass index (rs = 0.272, P = 0.006)
and serum low-density lipoprotein cholesterol (P = 0.006). There was a
significant negative correlation between serum 25(OH)D and total daily dose of
insulin prescribed (rs = -0.257, P = 0.042). Regression analyses showed that
every 10-nmol/L decline in serum 25(OH)D was associated with a 0.2% increase in
HbA1c . CONCLUSIONS: Lower serum 25(OH)D was associated with poorer glycemic
control and higher insulin use among multi-ethnic Asians with type 2 diabetes and
stage 3-4 CKD.
PMID- 28519966
TI - Understanding the relationship between olfactory-specific quality of life,
objective olfactory loss, and patient factors in chronic rhinosinusitis.
AB - BACKGROUND: Chronic rhinosinusitis (CRS) significantly impacts olfaction.
However, the relationship between objective olfaction and patient-reported
olfactory-specific quality of life (QOL) is not well understood. Furthermore,
objective olfactory testing can be time consuming, so we sought to determine if
patient-reported olfactory QOL can be used as screening tool for olfactory
dysfunction. METHODS: Olfactory dysfunction was evaluated in 109 patients with
CRS using the Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS)
and the Sniffin' Sticks Test, assessing for olfactory threshold, discrimination,
identification, and overall composite scores (TDI; composite score of threshold,
discrimination, and identification). Regression analysis was performed to
correlate olfactory metrics and patient and disease-specific factors with QOD-NS
scores. Optimal QOD-NS scores to classify patients based upon objective olfactory
function were established. RESULTS: Bivariate and multivariate regression
analyses of QOD-NS and CRS-associated comorbidities, objective measures of
disease, demographics, and CRS-specific QOL were performed. Non-white race,
depression, and worse 22-item Sino-Nasal Outcome Test (SNOT-22) scores correlated
with worse QOD-NS scores (p < 0.005). Worse TDI scores correlated with worse QOD
NS scores, and discrimination had the strongest correlation (p < 0.001). Mean +/-
standard deviation (SD) QOD-NS scores for normosmia, hyposmia, and anosmia were
44 +/- 7.2, 35.7 +/- 12.8, and 31.6 +/- 10.7, respectively. Receiver operating
characteristic curve analysis revealed an area under the curve of 0.770 (p <
0.001), and a QOD-NS cutoff of 38.5 to have maximal Youden's index to define
normal vs abnormal TDI score. CONCLUSION: In CRS, QOD-NS correlates with non
white race, depression, SNOT-22, and TDI score, with discrimination having the
strongest correlation. The QOD-NS also appears to be a feasible tool for
olfaction screening.
PMID- 28519968
TI - WE-E-BRB-06: Monte Carlo Calculations of the Skin Dose for Longitudinal Linac-MR
System Using Realistic Three-Dimensional Magnetic Field Modeling.
AB - PURPOSE: This study quantifies the effects of the magnetic field of a
longitudinal linac-MR system (B-field parallel to beam direction) on skin dose
due to the confinement of contaminant electrons, using Monte Carlo calculations
and realistic 3-D models of the magnetic field. METHODS: The complete realistic 3
D magnetic fields generated by the bi-planar Linac-MR magnet assembly are
calculated with the finite element method using Opera- 3D. EGSnrc simulations are
performed in the presence of ~0.6T and IT MRI fields that have realistic rapid
fall-off of the fringe field. The simulation geometry includes a Varian 600C 6MV
linac, the yoke and magnetic shields of the MRIs, and features an isocentre
distance of 126 cm. Phase spaces at the surface of a water phantom are scored
using BEAMnrc; DOSXYZnrc is used to score the resulting CAX percent depth-doses
in the phantom and the 2D skin dose distributions in the first 70 urn layer. For
comparison, skin doses are also calculated in the absence of magnetic field and
using a 1-D magnetic field with an unrealistic fringe field. The effects of field
size and air gap (between phantom surface and magnet pole) are also examined.
RESULTS: Analysis of the phase-space and dose distributions reveals that
significant containment of electrons occurs primarily close to the uniform
magnetic field region. The increase in skin dose due to the magnetic field
depends on the air gap, varying from 1% to 13% for air gaps of 5 to 31 cm,
respectively. The increase is also field-size dependent, varying from 3% at 20*20
cm2 to 11% at 5*5 cm2. CONCLUSIONS: Calculations based on various realistic MRI
3D magnetic-field maps that appropriately account for the rapid decay of the
fringe field show that the increase in the patient skin dose of a longitudinal
Linac-MR system is clinically insignificant.
PMID- 28519969
TI - WE-C-217BCD-03: Restricted Data Set Reconstruction Based on Respiration Quality
to Improve Prospectively Gated in Vivo Micro-CT of Mice.
AB - PURPOSE: Micro-CT is commonly employed for lung imaging of mice; prospective
gating allows for in-vivo imaging of free-breathing subjects. While this
technique is successfully executed for healthy animals, results are less
consistent for some disease models whose symptoms include irregular or unstable
respiration. The purpose of this work is to repair the quality of high-blur
images that arise from respiration instability using a retrospective method of
motion reduction which identifies the individual x-ray projection images
contributing most to the motion blur. Reconstructions were performed after the
exclusion of these projections (the so-called restricted set). METHODS: Sixteen
mice were imaged using field emission cone beam micro-CT and prospective gating
with a bellows-type respiration sensor. The scanner was operated in step-and
shoot mode; 400 projection images were acquired per scan. An algorithm was
developed to analyze the respiration trace file and segment the individual breath
corresponding to each projection image. We tested three different criteria to
define a bad breath shape (correlation, mean breath height, or mode breath
height), and restricted data set reconstructions were performed using each of
these criteria to exclude projections corresponding to bad breaths. Each
restricted set was compared against the full unrestricted data set image; the
slope perpendicular to the diaphragm was used as a quantitative assessment of
motion blur. RESULTS: All image sets saw a reduction in motion blur with at least
one restriction technique. In 22 of 27 images, improvement was measured
regardless of the removal criterion. Five percent total projection removal is
optimal; a more aggressive correction increases the likelihood of under-sampling
artifacts. CONCLUSIONS: Removing a subset of bad projections from otherwise
complete image sets measurably decreases motion blur in respiratory-gated
imaging. An approach based on breath height generally provides the best results.
The technique is applicable to a variety of imaging modalities.
PMID- 28519971
TI - WE-E-BRB-08: Establishing Comprehensive Quality Assurance Program for Volumetric
Modulated Arc Therapy - Clinical Study Using Control Point Analysis Software.
AB - PURPOSE: to validate the clinical effectiveness of Control Point Analysis (CPA)
software and establish a comprehensive quality assurance (QA) program for
Volumetric Modulated Arc Therapy (VMAT) treatment. METHODS: The comparison and
gamma analysis of ArcCHECKTM measurement and treatment planning system (TPS) is
considered one of the common methods for VMAT QA procedure. However, questions
like 'how QA discrepancies affect patient treatment? and ? what are the sources
of discrepancies? cannot be answered. In this study, 3DVHTM and recently
developed CPA software were tested for eight cases, including prostate, brain,
head&neck, and TGI 19 phantom cases. All VMAT plans used two arcs, with various
settings of couch rotation, collimator rotation, and splitting fields. Each
single arc was equally divided into 24 sub-arcs and doses of sub-arcs were
exported for CPA analysis. Gamma analyses (3mm/3%) were compared using the
ArcCHECK dose, single arc doses, sub-arc doses, and 3DVH patient's dose estimated
by Planned Dose PerturbationTM (PDP) algorithm. RESULTS: ArcCHECK composite dose
analyses were consistent with CPA sub-arc analysis for most cases. 3DVH generally
showed higher passing rate in dose voxel-by-voxel comparison. Cases with failed
QA were further analyzed by CPA for each sub-arc to reveal the sources of dose
discrepancies, whether they are mechanical errors (i.e. leaf motion failure) or
dosimetric modeling errors (i.e. elongated beam spot size or incorrect dynamic
leaf gap). CPA analysis showed values for cases with passed QA to detect small
discrepancies caused by failed MLC which was otherwise smeared out in the
composite dose comparison. CONCLUSIONS: CPA analysis expands QA process to a
greater level of details without additional work by users. With the additions of
CPA analysis and 3DVHTM, one can establish a comprehensive VMAT QA program with
detailed mapping of composite dose passing rate, the estimated effect of
discrepancies on patients, and possible sources of discrepancies.
PMID- 28519970
TI - WE-E-213CD-03: Inverse-Consistent Symmetric Registration of Inner Colon Surfaces
Derived from Prone and Supine CT Colonography.
AB - PURPOSE: Robust registration of prone and supine colonie surfaces acquired during
CT colonography may lead to faster and more accurate detection of colorectal
cancer and polyps. Any directional bias when registering one surface to the other
could precipitate incorrect anatomical correspondence and engender reader error.
Despite this, non-rigid registration methods are often implemented
asymmetrically, which could negatively influence the registration. We aimed to
reduce directional bias and so increase robustness by adapting a cylindrical
registration algorithm to be both symmetric and inverse-consistent. METHODS: The
registration task can be simplified by mapping both prone and supine colonie
surfaces onto regular cylinders. Spatial correspondence can then be established
in cylindrical space using the original surfaces' local shape indices. We
implemented a symmetric formulation of the popular non-rigid B-spline image
registration method in cylindrical space. A symmetric similarity measure computes
the sum of squared differences between both cylindrical representations of prone
to-supine and supine-to-prone directions simultaneously. Inverse consistency of
the transformation is enforced by adding an appropriately weighted penalty term
to the optimisation function. RESULTS: We selected 8 CT colonography patient
cases with marked variation in luminal distension and surface morphology. We
randomly allocated 4 of these for tuning an optimal set of registration
parameters and 4 for validation. The mean inverse-consistency error was reduced
by 32% from 4.8mm to 3.2mm by the new symmetric formulation. The mean
registration error improved from 8.2mm to 7.3mm for 330 manually chosen reference
points on the 4 validation sets. CONCLUSIONS: A symmetric formulation of prone
and supine surface registration improves the quality of registration. Information
from both prone-to-supine and supine-to-prone directions helps enforce
convergence towards a more accurate solution due to reduced directional bias. A
more robust and accurate registration will facilitate interpretation of CT
colonography and has the potential to improve existing computer-aided detection
methods. The authors gratefully acknowledge financial support for this work from
the NIHR program: a?oeImaging diagnosis of colorectal cancer: Interventions for
efficient and acceptable diagnosis in symptomatic and screening populationsa?.
PMID- 28519972
TI - WE-C-217BCD-05: A Novel Interpolation Method for the 3D Reconstruction of Cell
Structures.
AB - PURPOSE: To develop a new interpolation method for accurate 3D reconstruction of
cell morphology from laser scanning confocal microscope (LSCM) image data.
METHODS: Current techniques are based on the assumption that pixel intensity or
contour shapes of images change linearly in the interpolation direction. Gray
value and position of the pixel in interpolated image slice are obtained through
weighted average calculation with gray-values and distances of corresponding
pixels in two adjacent original image slices, only information from adjacent
image slices is considered, often fail to meet the need of 3D reconstruction for
cells because of the complex cell morphology. The new method interpolates
cellular organelle contours in polar coordinate system. Coordinate system origin
is chosen to be the mass center weighted by pixel intensity instead of
conventional geometric center, contour points of the organelle is sampled by
their angles first and fitted with uniform cubic B-spline to perform
interpolation. For complex organelle structures such as branched nuclei, a
special method combining morphological information and corner detection technique
based on curvature scale space has been developed to solve the contour division
and related problems. New method was applied to confocal images of 130 different
cells acquired with an LSCM system (LSM510, Zeiss), sampling step was set as 0.5
MUm in longitudinal direction, pixel size in horizontal plane was 0.07 MUm and
the resolution was 512*512. Marching cubes algorithm was used for 3D
reconstruction. RESULTS: Experiments showed that reconstructed 3D images with new
method have much smoother and more valid organelle surfaces for both cytoplasm
and nucleus than those from conventional methods. CONCLUSIONS: The new
interpolation method can significantly improve the quality of 3D reconstruction
and serve as a valid and effective tool for quantitative study of 3D cell
morphology in radiation biology and other areas of life science.*support by NSFC-
81171342. Supported by the National Science Foundation of China (NSFC- 81171342).
PMID- 28519973
TI - WE-E-213CD-05: A Non-Rigid Image Registration Algorithm That Accommodates Organ
Segmentation Error.
AB - PURPOSE: To introduce a new deformable image registration algorithm based on
surface matching that accommodates organ delineation error in daily Cone-beam CT
images based on a priori knowledge of inter-observer segmentation uncertainty.
METHODS: The dataset includes four prostate cancer patients who underwent primary
external beam radiotherapy and had tumors that were confined to the prostate. All
imaging was performed without intravenous contrast. Organ surface segmentation
errors in a multiple observer-contouring study on the pelvic organs in Fan-beam
CT (FBCT) and Cone-beam CT (CBCT) were estimated from the training dataset. A
novel deformable image registration algorithm is presented where the organ
surface matching is penalized by this error. Portions of the organ surface that
are delineated reliably are used to guide the registration whereas the portions
that are highly uncertain are ignored. This approach reduces the impact of
delineation errors in CBCT. An evaluation experiment compares three algorithms,
namely intensity-only registration (INT), equally-weighted surface and image
registration (EWSIR) and the proposed uncertainty- weighted surface and image
registration. RESULTS: The surface dissimilarity was reduced from 0.172 to 0.134,
0.043 and 0.044 respectively after registration. The Jacobian of the
transformation found by the proposed method was closer to one than that of EWSIR
in the prostate. CONCLUSIONS: In prostate external-beam radiotherapy, slice-by
slice 2D manual contouring has variable spatial accuracy. For deformable image
registration methods that match segmented surfaces, regions of high inaccuracy
can misguide the registration. In contrast to the image registration methods
where the FBCT and CBCT surfaces (or other features) are assumed to be exact, our
method takes this uncertainty into account. Preliminary results show an improved
registration performance suggesting a potential use in IGRT. This work was
supported by National Cancer Institute Grant No. P01 CA 116602.
PMID- 28519974
TI - WE-C-217A-04: An Analysis of Recent Literature Regarding Radiation Risk.
AB - The peer review process screens scientific articles for merit prior to acceptance
or rejection for publication. After publication the process continues with
scrutiny by other researchers as expressed in letters to the editor and other
scientific research that either affirms or denies findings. Research into
radiation effects directly affects the use of ionizing radiations in medicine.
The quality of peer review of articles on radiation effects is therefore critical
to the practice of medicine. This presentation will examine adequacy of peer
review regarding recent articles on radiation effects that have appeared in the
peer-reviewed literature. The purpose is to examine what factors in research
techniques and analyses contribute to the quality and believability of the
findings. Learning Objectives 1. To gain insight into the critical evaluation of
scientific literature on bio effect s 2. To understand how to distinguish
causation from correlation or association.
PMID- 28519975
TI - WE-E-218-01: Writing and Reviewing Papers in Medical Physics.
AB - : There is an art to writing a scientific paper so that it communicates
accurately, succinctly, and comprehensively. Developing this art comes with
experience, and sharing that experience with younger physicists is an obligation
of senior scientists, especially those with editorial responsibilities for the
journal. In this workshop, the preparation of a scientific manuscript will be
dissected so participants can appreciate how each part is developed and then
assembled into a complete paper. Then the review process for the paper will be
discussed, including how to examine a paper and write an insightful and
constructive review. Finally, we will consider the challenge of accommodating the
concerns and recommendations of a reviewer in preparing a revision of the paper.
A second feature of the workshop will be a discussion of the process of
electronic submission of a paper for consideration by Medical Physics. The web
based PeerX-Press engine for manuscript submission and management will be
examined, with attention to special features such as epaps and line-referencing.
Finally, new features of Medical Physics will be explained, such as Vision 20/20
manuscripts, Physics Letters and the standardized formatting of book reviews.
LEARNING OBJECTIVES: 1. Improve the participants' abilities to write a scientific
manuscript. 2. Understand the review process for Medical Physics manuscripts and
how to participate in and benefit from it. 3. Appreciate the many features of the
PeerX-Press electronic management process for Medical Physics manuscripts. 4.
Develop a knowledge of new features of Medical Physics.
PMID- 28519976
TI - WE-E-BRB-01: A Mathematical Model of the Optical Density Growth of EBT2 Film
after Proton Irradiation.
AB - PURPOSE: Gafchromic EBT2 is being used for radiation dosimetry including photon,
electrons and recently in proton beams, based on its color changes from
transparent to blue due to polymerization. It is critical to understand the
temporal response of the polymerization after irradiation to proton beam for more
accurate dosimetric results with EBT2. METHODS: Five small pieces cut from the
same sheet (lot no. A08060905A) were irradiated with different doses (2 - 10 Gy)
using a clinical proton beam with range 16 cm and spread-out-Bragg-peak 10 cm. An
EPSON flatbed 10000XL was used for digitization in 48 bit color RGB images. The
films were kept in the same position on the scanner for each scan. Within a 6-day
period, measurements were taken every 3 minutes for the first hour, every 5 to 30
minutes for the first 1-12 hours and then randomly after 12 hours. Red, green and
blue frequency read out of the scanner for each film was analyzed in ImageJ
software. RESULTS: A mathematical function (netOD =a + beta (1-exp (-t/Ta)) +
gamma (1-exp (-t/Tb)) was used to describe the temporal response. The
polymerization is time dependent with two time constants, Ta (25 minutes) and Tb
(1000 minutes), a, beta, and gamma are dose dependent parameters. The percentage
of OD change per 10 minutes remains less than 1% after the first hour. A 7%-ll%
increase in the net OD was observed within the first 12 h when irradiated within
10 Gy, comparable to the 9% reported for EBT films. CONCLUSIONS: The growth of OD
post-irradiation may be explained by the rapid polymerization in EBT2 film. This
characteristic can be described by a double exponential function which may be
used to correct the temporal coloration effect to improve the accuracy for
radiation dosimetry using EBT2 film in proton beam.
PMID- 28519977
TI - WE-E-BRA-01: Introduction to Treatment Assessment of Radiation Therapy Using MR
Functional Imaging and Its Application to Intracranial Stereotactic Radiosurgery.
AB - : Recent developments in MRI have substantially improved its performance, making
it a potentially powerful tool for not only diagnosis but also therapy. Treatment
assessment using MR functional imaging is the process of using MR functional
imaging before and/or during and/or after a course of radiation therapy (RT) to
assess treatment responses and as such to optimize therapeutic outcome. Various
MR functional techniques including, but not limited to, diffusion weighted
imaging (DWI), diffusion tensor imaging (DTI), MR spectroscopy (MRS) and dynamic
contrast enhanced (DCE) imaging, have been investigated to assess therapeutic
outcome in radiotherapy. DCE-MRI uses fast imaging and contrast material to
assess changes in the microvascular environment. MRS can be used to assess non
invasively biochemical changes caused by RT. Diffusion imaging techniques are
used to assess the changes of cellular density and neural fibers caused by RT. In
this lecture, the application of functional imaging to the assessment of
stereotactic radiosurgery is illustrated. Stereotactic radiosurgery (SRS) is
effective in treating brain tumors, but radiation may cause injury to normal
brain tissues (e.g., white matter), compromising sensory and neurocognitive brain
functions. DTI can be used to track neural fibers and assess radiation-induced
damages in white matter. Furthermore, DCE-MRI can be used to interrogate tumor
biology and treatment-related changes in tumor vasculature after SRS. These
Issues related to treatment-related changes will be discussed. This lecture will
provide an overview of the MR functional imaging along with its application to
the assessment of stereotactic radiosurgery. LEARNING OBJECTIVES: 1. Understand
the principles of MR functional imaging techniques 2. Understand the issues
related to MR functional imaging 3. Understand the clinical application of MR
functional imaging in assessing treatment response of SRS.
PMID- 28519978
TI - WE-C-217BCD-09: Compressed Sensing in PET Imaging with Partial Detector Rings.
AB - PURPOSE: Investigate the possibility of reducing the number of PET detector
elements per ring (introduce gaps) while maintaining image quality by employing
compressed sensing techniques. METHODS: A uniform Ge-68 phantom was imaged on a D
RX PET/CT scanner twice; once with all detectors operational (baseline) and once
with 8 equidistant detector blocks turned off (partially sampled [PS], 11%
detectors off. The resulting PS sinogram was then decomposed in two different
components, each sparsely represented in a specific transform domain. An
iterative optimization technique was then used to recover the PS sinogram based
on the solution of a combination of underdetermined system of equations and block
coordinated relaxations. In addition, the total variation is minimized for the
first component to direct it into a piece-wise smooth model. Finally the two
components were summed to obtain the sinogram which was used to compare with the
original PS sinogram. Comparison was done only for existing sinogram pixel
values. This process was repeated iteratively until a RMS error of 5% or a total
of 100 iterations were reached. For each iteration update, the values of the
pixels corresponding to the missing detectors were obtained from the previous
iteration while the remaining pixel values were extracted from the baseline
sinogram. The resultant corrected sinograms where then reconstructed using OSEM
and FBP and the corresponding images for full and PS sinograms were compared
using mean and max activity concentration in a ROI placed centrally over the
phantom. RESULTS: For OSEM (FBP) reconstruction, the mean and max activity
concentration difference were -0.06% (-0.02%) and 3.7% (5.5%) respectively when
compared to baseline. CONCLUSIONS: Compressed sensing seems to have the ability
to recover PS PET data. Such an approach can potentially be used to generate PET
images with accurate quantitation while reducing number of detectors/ring.
PMID- 28519979
TI - WE-E-213CD-09: Multi-Atlas Fusion Using a Tissue Appearance Model.
AB - PURPOSE: To improve multi-atlas based auto-segmentation by integrating a tissue
appearance model with the Simultaneous Truth and Performance Level Estimation
(STAPLE) algorithm to perform multi-atlas fusion. METHODS: Ten head-and-neck
planning CT images were acquired (resolution: 1.0*1.0*2.5mm3 ) and the parotid
glands were contoured manually by a head-and-neck oncologist. We performed 10
leave-one-out tests by using one patient as test patient and the rest of 9
patients as atlases. Deformable registration was first applied to transform the
atlas parotid contours to the test image one by one. The STAPLE algorithm was
initialized by a parotid tissue appearance model, which was estimated from the
test image and encoded the intensity information of parotid glands. The
individual deformed contours were then fused using the STAPLE algorithm to
produce a best approximation of the true contour. The tissue appearance model was
also applied to a deformable model segmentation to further refine the fused
contours. RESULTS: The multi-atlas fusion using the tissue appearance model
produced an average Dice coefficient of 85.2%+/-3.1% (left parotid) and 84.9%+/
3.9% (right parotid) over the 10 tests between the auto-contour and the manual
contour, and an average mean surface distance of 1.6+/-0.3mm and 1.6+/-0.4mm for
left and right parotids respectively. This demonstrated a good agreement between
the manual contours and the auto- delineated contours. Our results also showed
that, without using the tissue appearance model, the auto-delineated parotid
contours might include nearby bony structures; however, using the appearance
model was able to correct this problem. CONCLUSIONS: Including the intensity
information using a tissue appearance model into STAPLE algorithm for multi-atlas
fusion showed improvement in refining the anatomical boundaries in the multi-
atlas based auto-segmentation.
PMID- 28519980
TI - WE-D-213AB-03: Preparing for the ABR Diagnostic Medical Physics Board Exams -
Oral Exam.
AB - : Part III (oral exam) is the final part of ABR board exam for Diagnostic Medical
Physics. In this exam, each of five oral examiners questions the candidate in
each of five question categories. Oral exam has unique challenges to the
candidate compared with the written exams. The candidate is expected to have not
only adequate knowledge on each aspect of imaging physics, but also extensive
clinical experience on different imaging modalities. The candidate needs to
demonstrate her/his knowledge and clinical experience by correctly and
effectively answering specific questions during the exam. Depending on the
response of the candidate to original question, different follow-up questions are
usually asked. Therefore, the interaction with examiners plays a critical role in
the oral exam. The format and question categories of the oral exam in diagnostic
medical physics will be reviewed. Study materials and effective study methods
will be discussed. Practical tips on answering questions and interactions with
examiners during the oral exam will also be shared. LEARNING OBJECTIVES: 1.
Understand the format and scope of oral exam. 2. Develop an effective method for
exam preparation. 3. Learn how to effectively answer questions and interact with
examiners during the exam.
PMID- 28519981
TI - WE-E-BRB-05: A Novel Detector Dose Calculation Model for in Vivo Delivery
Verification of IMRT Treatments.
AB - PURPOSE: Exit 2D detectors are widely used in clinics as a tool for pre-
treatment field verification. It is desired to have accurate modeling of the
detector dose for each IMRT plan with patient geometry for in-vivo delivery
verification. We propose a novel hybrid of model and measurement based methods to
estimate the detector dose using the information from TPS and plan/verification
CT. METHODS: Our approach is based on the generalized equivalent field size
(GEFS) method. It requires two commissioning tables for various square fields
(l*l, 2*2, ...40*40): the percent depth dose (PDD) table and the detector
correction factor (DDCF) table. PDDs are retrieved from the treatment planning
system (TPS), and DDCFs are reconstructed from measurement with various field
sizes and air gaps (from 5 cm to 50 cm). GEFS models the detector point dose as
the superposition of annular contribution of the fluence map, which is retrieved
from the TPS. Correction on the radiological path length is calculated through
ray-tracing the patient CT. Corrections on the air gap between the couch and
detector and detector response are applied via table lookup on PDD and DDCF.
RESULTS: We validated the proposed method using TPS with extended geometry and
direct clinic measurements for both regular and IMRT fields, various phantom and
patient geometry. For all calculations, more than 98% of pixels pass the gamma
index with criteria of 3%, 3mm. Each calculation took only a few seconds on a
single PC. CONCLUSIONS: We proposed a novel detector dose calculation method that
can be applied for arbitrary IMRT field and arbitrary patient geometry. The
calculation is simple and fast and when compared with detector measurement during
IMRT treatment, makes in- vivo delivery verification and dose reconstruction
feasible.
PMID- 28519982
TI - WE-C-217BCD-02: Design of an MR Compatible Rotating Anode X-Ray Tube.
AB - PURPOSE: To design a rotating anode X-ray tube capable of operating in strong
magnetic field environments. This tube design can be used in 'close proximity"
hybrid X-ray/MR system geometries where the imaging fields of view are separated
by only ~1.2 meters. METHODS: Existing rotating anode X-ray tube designs fail in
strong magnetic field environments because the fields alter the electron
trajectories in the tube and act as a brake on the induction motor, reducing the
rotation speed of the anode. We propose an X- ray tube design that utilizes
optimized resistive coils to shield a fraction of the MR fringe field. The
remainder of the correction is performed using bias voltages on electrodes
adjacent to the x-ray tube filament. Furthermore, we replace the induction motor
with a novel motor design that is analogous to a three-phase brushed DC motor
with the MR fringe field serving as the stator field. RESULTS: Space charge
simulations of the electron optics show that the combined
magnetostatic/electrostatic method can correct for a magnetic field strength of
152 mT with approximately 590 A/cm2 applied to the shielding coils and a 35 kV
potential difference applied to the bias electrodes. A prototype of the motor
design was machined and assembled. The performance of this prototype motor was
evaluated at various magnetic field strengths, and was found to accelerate to the
minimum operating speed of 3000 rpm in 10 seconds for an external field of 60 mT.
CONCLUSIONS: The space charge simulations validate that the electron trajectories
can be controlled using our combined approach. Testing of the motor prototype
demonstrates that our design outperforms existing induction motors in strong
magnetic field environments. Integrating this design with our modified flat panel
detector will allow, for the first time, a "close proximity" hybrid system in
which imaging performance is not compromised. NIH R01 EB007626 Richard M. Lucas
Foundation Stanford Bio-X Fellowship.
PMID- 28519983
TI - WE-E-213CD-02: Gaussian Weighted Multi-Atlas Based Segmentation for Head and Neck
Radiotherapy Planning.
AB - PURPOSE: To develop a multi-atlas segmentation strategy for IMRT head and neck
therapy planning. METHODS: The method was tested on thirty-one head and neck
simulation CTs, without demographic or pathology pre-clustering. We compare Fixed
Number (FN) and Thresholding (TH) selection (based on normalized mutual
information ranking) of the atlases to be included for current patient
segmentation. Next step is a pairwise demons Deformable Registration (DR) onto
current patient CT. DR was extended to automatically compensate for patient
different field of view. Propagated labels are combined according to a Gaussian
Weighted (GW) fusion rule, adapted to poor soft tissues contrast. Agreement with
manual segmentation was quantified in terms of Dice Similarity Coefficient (DSC).
Selection methods, number of atlases used, as well as GW, average and majority
voting fusion were discriminated by means of Friedman Test (a=5%). Experimental
tuning of the algorithm parameters was performed on five patients, deriving an
optimal configuration for each structure. RESULTS: DSC reduction was not
significant when ten or more atlases are selected, whereas DSC for single most
similar atlas selection is 10% lower in median. DSC of FN selection rule were
significantly higher for most structures. Tubular structures may benefit from
computing average contour rather than looking at the singular voxel contribution,
whereas the best performing strategy for all other structures was GW. When half
database is selected, final median DSC were 0.86, 0.80, 0.51, 0.81, 0.69 and 0.79
for mandible, spine, optical nerves, eyes, parotids and brainstem respectively.
CONCLUSION: We developed an efficient algorithm for multiatlas based segmentation
of planning CT volumes, based on DR and GW. FN selection of database atlases is
foreseen to increase computational efficiency. The absence of clinical pre
clustering and specific imaging protocol on database subjects makes the results
closer to real clinical application. "Progetto Roberto Rocca" funded by the
Fondazione Fratelli Agostino and Enrico Rocca, Italy.
PMID- 28519984
TI - WE-C-217A-01: Risk Estimation versus Risk Perception.
AB - : The recent attention in the scientific and popular press to the potential risks
associated with ionizing radiation from medical imaging has resulted in some
patient becoming unwilling to undergo medically appropriate procedures that use
ionizing radiation. Scientific data on the magnitude of both potential risks and
benefits are not always successful in allaying patient concerns, even though the
potential risks are very small and the potential benefits are very large. An
understanding of the psychological factors affecting the perception of risk helps
to explain this behavior. For patients to feel comfortable with medical
procedures involving ionizing radiation, they must be believe that their medical
providers have their best interest in mind, that the ordered procedure is
medically appropriate and may help their doctor in managing their care, and that
those providing the imaging services are actively engaged in efforts to ensure
patient safety. LEARNING OBJECTIVES: 1. Differentiate between risk estimation and
risk perception 2. List several factors that affect a person's perception of risk
3. Describe some of the consequences that may occur when patients do not feel
that they are safe.
PMID- 28519985
TI - WE-E-217A-02: Methodologies for Evaluation of Standalone CAD System Performance.
AB - Standalone performance evaluation of a CAD system provides information about the
abnormality detection or classification performance of the computerized system
alone. Although the performance of the reader with CAD is the final step in CAD
system assessment, standalone performance evaluation is an important component
for several reasons: First, standalone evaluation informs the reader about the
performance level of the CAD system and may have an impact on how the reader uses
the system. Second, it provides essential information to the system designer for
algorithm optimization during system development. Third, standalone evaluation
can provide a detailed description of algorithm performance (e.g., on subgroups
of the population) because a larger data set with more samples from different
subgroups can be included in standalone studies compared to reader studies.
Proper standalone evaluation of a CAD system involves a number of key components,
some of which are shared with the assessment of reader performance with CAD.
These include (1) selection of a test data set that allows performance assessment
with little or no bias and acceptable uncertainty; (2) a reference standard that
indicates disease status as well as the location and extent of disease; (3) a
clearly defined method for labeling each CAD mark as a true-positive or false
positive; and (4) a properly selected set of metrics to summarize the accuracy of
the computer marks and their corresponding scores. In this lecture, we will
discuss various approaches for the key components of standalone CAD performance
evaluation listed above, and present some of the recommendations and opinions
from the AAPM CAD subcommittee on these issues. Learning Objectives 1. Identify
basic components and metrics in the assessment of standalone CAD systems 2.
Understand how each component may affect the assessed performance 3. Learn about
AAPM CAD subcommittee's opinions and recommendations on factors and metrics
related to the evaluation of standalone CAD system performance.
PMID- 28519986
TI - WE-C-217BCD-04: Multimodality Imaging of Breast Cancer Experimental Lung
Metastasis.
AB - PURPOSE: Metastatic breast cancer (MBC) is incurable. The clinical gold standard
for assessing tumor microvessel density (MVD), an independent prognostic marker
in MBC, is CD 105 staining. The goal of this study is to develop a positron
emission tomography (PET)/near-infrared fluorescent (NIRF) probe for imaging of
CD105 expression in MBC (i.e. non-invasive measurement of MVD), as well as other
applications such as early detection of metastasis, intraoperative guidance, etc.
METHODS: TRC105, a chimeric anti-CD105 mAb, was dual-labeled with a NIRF dye and
89 Zr to yield 8 9 Zr-Df-TRC105-800CW. Luciferase-transfected 4T1 murine breast
cancer cells were injected intravenously into female BALB/c mice to establish a
lung MBC model. Bio luminescence imaging (BLI) was carried out to non- invasively
monitor the lung tumor burden. Comprehensive in vivo/ex vivo studies were
performed to investigate 8 9 Zr-Df-TRC105-800CW in this MBC model. Cetuximab was
used as an isotype-matched control. RESULTS: Radiolabeled TRC105 has high tumor
uptake in many tumor types in addition to MBC (e.g. pancreatic/prostate cancer
and brain tumor), revealing broad clinical potential for TRC105-based agents.
FACS analysis of HUVECs showed no difference in CD 105 binding between TRC105 and
Df- TRC105-800CW. PET imaging revealed that 4T1 lung tumor uptake of 89 Zr-Df
TRC105-800CW was 8.7+/-1.4,10.9+/-0.5, and 9.7+/-1.1 %ID/g at 4, 24, and 48 h
post-injection (n = 4), with excellent tumor contrast. Bio distribution studies,
blocking, control studies with 8 9 Zr-Df-cetuximab- 800CW, ex vivo BLI/PET/NIRF
imaging, and histology all confirmed CD 105 specificity of the tracer. NIRF
imaging-guided removal of 4T1 tumors with Df-TRC105-800CW in a subcutaneous model
was also straightforward. CONCLUSIONS: We report the first PET/NIRF imaging of
CD105 expression in a MBC model. Broad clinical potential of TRC105- based agents
was shown in many tumor types, which also enabled early detection of small
metastases and provided intraoperative guidance for tumor removal.
PMID- 28519987
TI - WE-E-213CD-04: CT to Cone-Beam CT Deformable Registration With Simultaneous
Intensity Correction.
AB - PURPOSE: To develop and validate a robust CT to cone-beam (CBCT) deformable image
registration algorithm that can handle CBCT artifacts and intensity
inconsistency, and thus can yield accurate registration results. METHODS: We
propose a new algorithm called Deformation with Intensity Simultaneously
Corrected (DISC). DISC distinguishes itself from the original demons by
performing an intensity correction procedure on the CBCT image at every iteration
step of demons registration. Specifically, the intensity correction of a voxel in
CBCT is achieved by matching the first and the second moments of the image
intensities inside a patch around this voxel with those on the CT image. It is
expected that such a strategy can remove artifacts in the CBCT image, as well as
ensuring the intensity consistency between the two modalities and hence
facilitating the registration process. DISC is implemented on computer graphics
processing units (GPUs) using the compute unified device architecture (CUDA)
programming environment. The performance of DISC has been qualitatively and
quantitatively evaluated on a simulated patient case and six head-and- neck
cancer patient data. RESULTS: Visual inspection shows that original demons
distorts the tissues after registration, especially in regions which are heavily
degraded by artifacts. DISC, on the other hand, can effectively register CT and
CBCT image even in regions contaminated by severe artifacts. The intensity
corrected CBCT that extracted from the last iteration of DISC is artifact-free
and has similar histogram distribution with the deformed CT. CONCLUSIONS: We have
developed a robust CT to CBCT deformable image registration method that properly
deals with the CBCT artifacts and intensity inconsistency, and thus yields
accurate registration results. This work is supported in part by the University
of California Lab Fees Research Program, the Master Research Agreement from
Varian Medical Systems, Inc., and the grants from the National Natural Science
Foundation of China (No.30970866).
PMID- 28519988
TI - WE-C-217A-03: Biology versus Epidemiology: The Need for an Integrated Model of
Radiation Risk.
AB - : The lifetime attributable risk estimates from the National Academy of Sciences
BEIR VII report have been used by a number of authors to estimate cancer
mortality caused by radiation exposure from medical diagnostic radiology exams.
This controversial practice assumes that the dose response relationship between
radiation and cancer is linear with no threshold (LNT). For purposes of
protecting public health, use of the LNT model is widely accepted. But is it
appropriate for estimating risk to individuals exposed to low doses of radiation
from medical procedures? Radiation biology research demonstrates that not all
biological processes are linear. Italso has provided data that support not only
LNT but supra linear and sub linear response models. Results from epidemiology
studies can also be used to support the use of any of these models, but the
confidence intervals are much larger. Since we can't prove which model is
correct, for purposes of protecting patients we assume that any exposure has the
potential for harm and we use optimization to keep exposures as low as reasonably
achievable.Several areas of research are contributing insight into this dilemma,
but they still leave several important questions unanswered: * How can we
accurately extrapolate low-dose biological effects generated in the laboratory to
risk in a human? * Is extrapolation from high dose, high dose rate, acute
exposures appropriate when human exposures are primarily chronic low dose
exposures. Epidemiology alone is unlikely to provide information that will
resolve this dilemma. The numbers of individuals required in a sample are too
large, and the homogeneity among subjects is lacking. Reliance on radiation
biology research alone is problematic because the research is focused primarily
on mechanisms and not risk. This paper will present an overview of the issues and
suggest areas of research that may contribute to our understanding of the level
of risk associated with low doses of medical radiation. LEARNING OBJECTIVES: 1.
List the current biological mechanisms that are affected by low doses of ionizing
radiation. 2. Describe the dilemma of risk extrapolation based on current
knowledge of biological effects of radiation. 3. Discuss the limitations of
extrapolating lifetime attributable risk estimates to cancer mortality for low
dose medical procedures.
PMID- 28519989
TI - WE-E-217A-04: Training and QA Procedures for Using CAD Systems.
AB - : Computer-aided detection/diagnosis (CAD) devices for radiology are becoming
increasingly available for clinical use. To achieve the highest possible benefit
from CAD systems, best practices are required for clinical implementation and use
of CAD. This lecture will discuss four areas of interest to the medical physics
community pertaining to CAD best practices: off-label use and pitfalls, user
training, QA of CAD use, and academic opportunities for quality assurance (QA)
research. FINANCIAL DISCLOSURE: Patent royalties from and research agreement with
iCAD; software license to Translational Sciences Corporation. LEARNING
OBJECTIVES: 1. Understand benefits of PACS integration of CAD. 2. Identify
potential issues with off-label use of CAD. 3. Understand the importance of user
training relating to CAD devices. 4. Learn potential QA procedures to assure
proper use of CAD as designed. 5. Learn about areas of CAD user training and QA
that could benefit from further research.
PMID- 28519990
TI - WE-E-BRCD-01: SBRT Treatment Planning: Practical Considerations.
AB - : Stereotactic Body Radiation Therapy (SBRT) is being increasingly used in the
radiation oncology community to treat tumors in extra-cranial sites such as
spine, lung, liver, pancreas and prostate. There are well established RTOG
protocols (e.g. RTOG 0631 for spine, RTOG 0813 and 0915 for lung and RTOG 0438
for liver) that specify detailed requirements for treatment planning of SBRT
plans. SBRT plans have to meet strict criteria on maximum PTV dose, prescription
isodose, prescription isodose surface coverage, high dose spillage and
intermediate dose spillage in addition of the constraints of dose limiting organs
at risk. This lecture aims to educate members on treatment planning issues for
SBRT cases with concentration on strategies to create highly inhomogeneous dose
distributions inside the PTV and steep dose gradients in the surrounding normal
tissues. LEARNING OBJECTIVES: 1. What characteristics SBRT plans have and how
they are different from conventional fractionated radiotherapy plans. 2. For
IMRT/VMAT SBRT plans (such as spine SBRT plans that concave distributions around
the cord are required), we will discuss strategies that can be employed to
overcome many commercial treatment planning system's IMRT algorithms' intrinsic
penalty for inhomogeneous plans. Additional issues related to VMAT will be also
discussed. 3. For non-IMRT SBRT plans (such as many lung or liver cases where
target motion is a concern), we will discuss techniques to control dose
inhomogeneities and dose fall off. 4. We will also discuss policy and procedures
on SBRT patient setup and verification issues to ensure safe delivery of SBRT
treatments.
PMID- 28519991
TI - WE-E-BRB-11: Riview a Web-Based Viewer for Radiotherapy.
AB - PURPOSE: Collaborations involving radiotherapy data collection, such as the
recently proposed international radiogenomics consortium, require robust, web
based tools to facilitate reviewing treatment planning information. We present
the architecture and prototype characteristics for a web-based radiotherapy
viewer. METHODS: The web-based environment developed in this work consists of the
following components: 1) Import of DICOM/RTOG data: CERR was leveraged to import
DICOM/RTOG data and to convert to database friendly RT objects. 2) Extraction and
Storage of RT objects: The scan and dose distributions were stored as .png files
per slice and view plane. The file locations were written to the MySQL database.
Structure contours and DVH curves were written to the database as numeric data.
3) Web interfaces to query, retrieve and visualize the RT objects: The Web
application was developed using HTML 5 and Ruby on Rails (RoR) technology
following the MVC philosophy. The open source ImageMagick library was utilized to
overlay scan, dose and structures. The application allows users to (i) QA the
treatment plans associated with a study, (ii) Query and Retrieve patients
matching anonymized ID and study, (iii) Review up to 4 plans simultaneously in 4
window panes (iv) Plot DVH curves for the selected structures and dose
distributions. RESULTS: A subset of data for lung cancer patients was used to
prototype the system. Five user accounts were created to have access to this
study. The scans, doses, structures and DVHs for 10 patients were made available
via the web application. CONCLUSIONS: A web-based system to facilitate QA, and
support Query, Retrieve and the Visualization of RT data was prototyped. The
RIVIEW system was developed using open source and free technology like MySQL and
RoR. We plan to extend the RIVIEW system further to be useful in clinical trial
data collection, outcomes research, cohort plan review and evaluation.
PMID- 28519992
TI - WE-C-217BCD-08: Rapid Monte Carlo Simulations of DQE(f) of Scintillator-Based
Detectors.
AB - PURPOSE: Monte Carlo simulations of DQE(f) can greatly aid in the design of
scintillator-based detectors by helping optimize key parameters including
scintillator material and thickness, pixel size, surface finish, and septa
reflectivity. However, the additional optical transport significantly increases
simulation times, necessitating a large number of parallel processors to
adequately explore the parameter space. To address this limitation, we have
optimized the DQE(f) algorithm, reducing simulation times per design iteration to
10 minutes on a single CPU. METHODS: DQE(f) is proportional to the ratio, MTF(f)2
/NPS(f). The LSF-MTF simulation uses a slanted line source and is rapidly
performed with relatively few gammas launched. However, the conventional NPS
simulation for standard radiation exposure levels requires the acquisition of
multiple flood fields (nRun), each requiring billions of input gamma photons
(nGamma), many of which will scintillate, thereby producing thousands of optical
photons (nOpt) per deposited MeV. The resulting execution time is proportional to
the product nRun x nGamma x nOpt. In this investigation, we revisit the
theoretical derivation of DQE(f), and reveal significant computation time savings
through the optimization of nRun, nGamma, and nOpt. Using GEANT4, we determine
optimal values for these three variables for a GOS scintillator-amorphous silicon
portal imager. Both isotropic and Mie optical scattering processes were modeled.
Simulation results were validated against the literature. RESULTS: We found that,
depending on the radiative and optical attenuation properties of the
scintillator, the NPS can be accurately computed using values for nGamma below
1000, and values for nOpt below 500/MeV. nRun should remain above 200. Using
these parameters, typical computation times for a complete NPS ranged from 2-10
minutes on a single CPU. CONCLUSIONS: The number of launched particles and
corresponding execution times for a DQE simulation can be dramatically reduced
allowing for accurate computation with modest computer hardware. NIHRO1 CA138426.
Several authors work for Varian Medical Systems.
PMID- 28519993
TI - WE-E-213CD-08: A Novel Level Set Active Contour Algorithm Using the Jensen-Renyi
Divergence for Tumor Segmentation in PET.
AB - PURPOSE: Positron emission tomography (PET) presents a valuable resource for
delineating the biological tumor volume (BTV) for image-guided radiotherapy.
However, accurate and consistent image segmentation is a significant challenge
within the context of PET, owing to its low spatial resolution and high levels of
noise. Active contour methods based on the level set methods can be sensitive to
noise and susceptible to failing in low contrast regions. Therefore, this work
evaluates a novel active contour algorithm applied to the task of PET tumor
segmentation. METHODS: A novel active contour segmentation algorithm based on
maximizing the Jensen-Renyi Divergence between regions of interest was applied to
the task of segmenting lesions in 7 patients with T3-T4 pharyngolaryngeal
squamous cell carcinoma. The algorithm was implemented on an NVidia GEFORCE GTV
560M GPU. The cases were taken from the Louvain database, which includes contours
of the macroscopically defined BTV drawn using histology of resected tissue. The
images were pre-processed using denoising/deconvolution. RESULTS: The segmented
volumes agreed well with the macroscopic contours, with an average concordance
index and classification error of 0.6 +/- 0.09 and 55 +/- 16.5%, respectively.
The algorithm in its present implementation requires approximately 0.5-1.3 sec
per iteration and can reach convergence within 10-30 iterations. CONCLUSIONS: The
Jensen-Renyi active contour method was shown to come close to and in terms of
concordance, outperforms a variety of PET segmentation methods that have been
previously evaluated using the same data. Further evaluation on a larger dataset
along with performance optimization is necessary before clinical deployment.
PMID- 28519994
TI - WE-D-213AB-02: Preparing the ABR Diagnostic Exam: Part II.
AB - : Preparing for Part II of the Diagnostic Medical Physics American Board of
Radiology exam requires a different approach than studying for Part I of the
exam. As Part II is the first exam that splits apart the different medical
physics disciplines, it is unsurprising that the best preparation for the exam is
clinical experience. A well-rounded clinical physics training program and a
review of texts covering the fundamentals of the various imaging modalities
should leave examinees confident in their ability to successfully complete Part
II. Completion of a CAMPEP accredited residency program is excellent preparation
for Part II, and individuals sitting for the exam who have not completed a
residency would do well to gain as much clinical experience in the different
imaging modalities as possible. This presentation will focus on important
clinical experiences and topics to focus on and useful resources to review
diagnostic medical physics fundamentals in advance of taking Part II. LEARNING
OBJECTIVES: 1. Become familiar with useful refresher material for Part II 2.
Understand the importance of a broad and deep history of clinical experience 3.
Be able to identify relevant topics that may be included on the exam.
PMID- 28519995
TI - WE-E-BRB-04: Quantitative Dose Tracking Enabled Through a Novel Deformable 3D
Dosimeter.
AB - PURPOSE: To evaluate and investigate the feasibility of a new method for
validating dose tracking algorithms in deforming tissues using a novel deformable
3D dosimeter. METHODS: A novel deformable 3D Presage dosimeter is reported
consisting of a stretchy polyurethane matrix doped with radiochromic leuco-dye.
Two deformable cylindrical dosimeters (6 cm diameter, 5 cm long) were
manufactured and irradiated with a checkerboard arrangement of 5 mm square pencil
beams created by MLC fields. One dosimeter was irradiated under lateral
compression by 33% (6 cm down to 4 cm diameter) to simulate a deformed organ. A
second control dosimeter was irradiated with the same checkerboard pattern but
without deformation applied. High-resolution 3D dose distributions (isotropic 1
mm resolution) were obtained by optical-CT imaging. Physical dose deformation was
quantified by comparing checkerboard pencil beam shapes and positions in the
deformed and control dosimeters. RESULTS: Deformation of dose in the deformed
dosimeter was clearly visible in all 3 dimensions. The deformed checkerboard dose
pattern showed expansion of 16% - 46% along the axis of compression, with higher
expansion observed in the central regions of the dosimeter. Perpendicular to the
compression axis, the dose pattern contracted by 7% - 13%. Peak dose changes of
6% and +30% were observed parallel and perpendicular to the compression axis
respectively. Dose response was linear from 0-8 Gy. CONCLUSIONS: Dose tracking
was successfully quantified in a novel deforming 3D dosimeter. This capability
has potential as a powerful new method for validating deformable dose tracking
and registration algorithms. NCI R01CA100835.
PMID- 28519996
TI - WE-C-217BCD-01: Development of an Integrated Multimodal Imaging System (IMIS) for
Surgical Guidance.
AB - PURPOSE: To develop an intraoperative multimodal imaging system (IMIS) for
surgical guidance, combining gamma ray scintigraphy with a video camera system
for simultaneous real-time visible and near infrared fluorescence (NIRf) imaging.
METHODS: The gamma camera component has been tested in a pilot human study for
intraoperative SLN biopsy in melanoma patients. To characterize the optical
components, the spatial resolution of the visible light video camera, the depth
dependent visualization by the NIRf system of targets containing indocyanine
green (ICG) and the excitation radiation rejection of the NIRf system were
evaluated in bench-top tests. Spatial resolution was quantified using a USAF test
pattern and NIRf performance was evaluated using phantoms containing fluorescent
targets in mixtures of fat-emulsion (Intralipid) and india ink to simulate
optical transport in human tissue. The visible/NIRf system was also used to image
a live anaesthetized mouse model of breast cancer. RESULTS: Intraoperatively the
SiPM gamma camera detected 100% of positive lymph nodes. The visible light camera
system contrast transfer function is >10% up to 3.2 1p/mm. The NIRf image SNR
when imaging a 9.9 mm diameter lesion containing a 20 MUM ICG concentration is >
2 for lesion depths up to 8 mm. The current combination of excitation and
emission filters results in nearly complete rejection of backscattered light,
resulting in a leakage count rate less than 1% of the system dark count rate.
CONCLUSIONS: The optical component of the IMIS system demonstrates high spatial
resolution, excellent rejection of background excitation radiation, and good
target SNR for realistic tracer concentration and target depth. It is capable of
accurately coregistered video rate visible/NIRf imaging.
PMID- 28519997
TI - WE-E-213CD-01: Best in Physics (Joint Imaging-Therapy) - Evaluation of
Deformation Algorithm Accuracy with a Two-Dimensional Anatomical Pelvic Phantom.
AB - PURPOSE: To objectively evaluate the accuracy of 11 different deformable
registration techniques for bladder filling. METHODS: The phantom represents an
axial plane of the pelvic anatomy. Urethane plastic serves as the bony anatomy
and urethane rubber with three levels of Hounsfield units (HU) is used to
represent fat and organs, including the prostate. A plastic insert is placed into
the phantom to simulate bladder filling. Nonradiopaque markers reside on the
phantom surface. Optical camera images of these markers are used to measure the
positions and determine the deformation from the bladder insert. Eleven different
deformable registration techniques are applied to the full- and empty-bladder
computed tomography images of the phantom to calculate the deformation. The
applied algorithms include those from MIMVista Software and Velocity Medical
Solutions and 9 different implementations from the Deformable Image Registration
and Adaptive Radiotherapy Toolbox for Matlab. The distance to agreement between
the measured and calculated deformations is used to evaluate algorithm error.
Deformable registration warps one image to make it similar to another. The root
mean-square (RMS) difference between the HUs at the marker locations on the empty
bladder phantom and those at the calculated marker locations on the full-bladder
phantom is used as a metric for image similarity. RESULTS: The percentage of the
markers with an error larger than 3 mm ranges from 3.1% to 28.2% with the
different registration techniques. This range is 1.1% to 3.7% for a 7 mm error.
The least accurate algorithm at 3 mm is also the most accurate at 7 mm. Also, the
least accurate algorithm at 7 mm produces the lowest RMS difference. CONCLUSIONS:
Different deformation algorithms generate very different results and the outcome
of any one algorithm can be misleading. Thus, these algorithms require quality
assurance. The two-dimensional phantom is an objective tool for this purpose.
PMID- 28519998
TI - WE-C-217BCD-12: Irreversible Two-Tissue Compartment Model Fitting for Dynamic 18F
FDG PET: A Practical Comparison of Methods Using Simulated Time- Activity Data.
AB - PURPOSE: To compare techniques of fitting simulated Dynamic 18F-FDG PET time
activity curves to the irreversible two-tissue compartment model. The precision
and accuracy of various algorithms were assessed in the presence of measurement
error and with a practical focus on CPU time. METHODS: Dynamic PET analysis is
often applied to multiple individual voxels, leading to concerns regarding time
efficiency, yet a reluctance to compromise on accuracy. This study evaluates
selected fitting algorithms in terms of the precision/bias of fitted parameters
and run-time. As a standard for comparison, biological parameters were fixed at
typical values (K1=0.2, k2=0.25, k3=0.05, Kᵢ=0.3334). Tissue time-activity
curves were generated using the model equation and by incorporating activity/time
dependent Gaussian noise. The following algorithms were then applied: Genetic,
Conjugate Gradient (CG), Gradient Descent (GD), Simulated Annealing (SA),
Levenberg-Marquardt (LMQ), Gauss-Newton (GN), and Limited-BFGS (L-BFGS). Non
iterative, problem specific approaches were also considered: Patlak analysis (K?
only), and Blomqvist linearization (BL). Parameter accuracy and precision were
quantified with relative errors (REs). RESULTS: At typical noise levels, maximal
REs were >60% (resulting in |I'K?|>10%) for GD and SA, <20% for BL (|I'K?|<6%)
and Patlak (|I'K?|<4%), and <15% (|I'K?|<2%) with other methods. On average, the
highest fidelity parameter estimates (rate-constant REs<2.5%, |I'K?|<0.15%) were
attained with L-BFGS, GN, and LMQ. In contrast, the non-iterative methods
provided poorer estimates (RE between 1-7%), though run-time (<0.05 ms) was 100
1000x less. Using BL results as initial estimates for L- BFGS (BL+L-BFGS), GN
(BL+GN) or LMQ (BL+LMQ) yielded rapid convergence (<0.1 ms), while maintaining
superiority with respect to parameter bias. CONCLUSIONS: Poor choice of a fitting
algorithm may lead to significant errors in estimated kinetic parameters and/or
unpractically high computation times. Thus, our recommendation is the use of BL+L
BFGS, BL+GN or BL+LMQ, which is contrary to the gold standards, Patlak and LMQ
(alone), commonly seen in the literature.
PMID- 28519999
TI - WE-E-217A-01: CAD: Quality Assurance of CAD Systems Implemented in Clinical Use.
AB - PURPOSE: We propose a new metric called Distance Discordance (DD), which is
defined as the distance between two anatomic points from two moving images, which
are co-located on some reference image, when deformed onto another reference
image. METHODS: To demonstrate the concept of DD, we created a reference software
phantom which contains two objects. The first object (1) consists of a hollow box
with a fixed size core and variable wall thickness. The second object (2)
consists of a solid box of fixed size and arbitrary location. 7 different
variations of the fixed phantom were created. Each phantom was deformed onto
every other phantom using two B-Spline DIR algorithms available in Elastix and
Plastimatch. Voxels were sampled from the reference phantom [1], which were also
deformed from moving phantoms [2...6], and we find the differences in their
corresponding location on phantom [7]. Each voxel results in a distribution of DD
values, which we call distance discordance histogram (DDH). We also demonstrate
this concept in 8 Head & Neck patients. RESULTS: The two image registration
algorithms produced two different DD results for the same phantom image set. The
mean values of the DDH were slightly lower for Elastix (0-1.28 cm) as compared to
the values produced by Plastimatch (0-1.43 cm). The combined DDH for the H&N
patients followed a lognormal distribution with a mean of 0.45 cm and std.
deviation of 0.42 cm. CONCLUSIONS: The proposed distance discordance (DD) metric
is an easily interpretable, quantitative tool that can be used to evaluate the
effect of inter-patient variability on the goodness of the registration in
different parts of the patient anatomy. Therefore, it can be utilized to exclude
certain images based on their DDH characteristics. In addition, this metric does
not rely on 'ground truth' or the presence of contoured structures.
PMID- 28520000
TI - WE-E-217BCD-02: Update on the Upcoming ACR Digital Mammography QC Manual.
AB - PURPOSE: We propose a new metric called Distance Discordance (DD), which is
defined as the distance between two anatomic points from two moving images, which
are co-located on some reference image, when deformed onto another reference
image. METHODS: To demonstrate the concept of DD, we created a reference software
phantom which contains two objects. The first object (1) consists of a hollow box
with a fixed size core and variable wall thickness. The second object (2)
consists of a solid box of fixed size and arbitrary location. 7 different
variations of the fixed phantom were created. Each phantom was deformed onto
every other phantom using two B-Spline DIR algorithms available in Elastix and
Plastimatch. Voxels were sampled from the reference phantom [1], which were also
deformed from moving phantoms [2...6], and we find the differences in their
corresponding location on phantom [7]. Each voxel results in a distribution of DD
values, which we call distance discordance histogram (DDH). We also demonstrate
this concept in 8 Head & Neck patients. RESULTS: The two image registration
algorithms produced two different DD results for the same phantom image set. The
mean values of the DDH were slightly lower for Elastix (0-1.28 cm) as compared to
the values produced by Plastimatch (0-1.43 cm). The combined DDH for the H&N
patients followed a lognormal distribution with a mean of 0.45 cm and std.
deviation of 0.42 cm. CONCLUSIONS: The proposed distance discordance (DD) metric
is an easily interpretable, quantitative tool that can be used to evaluate the
effect of inter-patient variability on the goodness of the registration in
different parts of the patient anatomy. Therefore, it can be utilized to exclude
certain images based on their DDH characteristics. In addition, this metric does
not rely on 'ground truth' or the presence of contoured structures.
PMID- 28520001
TI - WE-C-217A-02: BEIR VII: What It Does and Doesn't Say.
AB - : Over the last 2 years, there has been considerable attention focused on the
potential cancer risks from medical imaging procedures, particularly with the
widespread use of multislice CT. Almost all studies rely upon the BEIR VII report
(Biological Effects of Ionizing Radiation panel formed under the auspices of the
National Academy of Sciences) to generate an estimate of the risk of cancer from
a given procedure. In doing so, most studies treat the BEIR VII report as a solid
basis of scientific evidence for estimation of cancer risk. In reality, a close
reading of this report shows that there are a large number of assumptions
inherent in all aspects of the estimates of cancer risk - a fact that is often
and clearly stated in the report. This presentation will review some of the
assumptions used by the BEIR panel to calculate cancer risk, including the impact
of different models (excess absolute risk vs. excess relative risk), the dose and
dose rate effectiveness factor (DDREF) and relative biological effectiveness
(RBE), on cancer estimates. Often lost in the discussion on medical exposure is a
reference level by which exposure levels can be compared to something that
unavoidable and impacts everyone on earth - background radiation. This
presentation will review the consequences of applying the BEIR model to
background radiation and known variations in levels of background radiation
throughout the U.S., and how the cancer rate from background compares with that
from medical imaging. LEARNING OBJECTIVES: 1. Understand the assumptions
underlying the BEIR VII report 2. Be able to compare the relative risks of
medical imaging procedures to that from background radiation.
PMID- 28520002
TI - WE-E-217A-03: Methodologies for Evaluation of Effects of CAD on Users.
AB - CAD devices are specifically designed to aid the user in the diagnostic process.
Therefore, the user (e.g., clinician) is an integral part of the CAD
interpretation process and the impact of CAD on users needs to be accounted for
in the assessment process. We use the term "reader performance assessment" to
denote a test specifically designed to estimate the performance of the user (or
reader) interpreting CAD as part of the diagnostic process. These reader
assessment studies are generally more indicative of clinical performance compared
with standalone testing. In this course, we will update the audience on the
latest approaches and metrics being used to assess the impact of CAD on user
performance, and discuss the opinions of the AAPM CAD subcommittee on the
evaluation methodologies, Learning Objectives: 1. To review the most common
reader performance assessment techniques and associated performance metrics
including the multireader multi-case (MRMC) study design. 2. To review the AAPM
CAD subcommittee's current thinking on best practices for performing and
analyzing CAD reader performance assessment studies. 3. To understand the
importance and limitations of various reader performance assessment approaches
and metrics for various classes of CAD devices.
PMID- 28520004
TI - WE-E-BRB-10: DosCheck - an Electronic Chart Checking Tool for Dosimetrists.
AB - PURPOSE: In addition to treatment planning, dosimetrists have to prepare
documentation and manually enter data in treatment management system (TMS) which
did not transfer or setup automatically. The required documents and data are
dependent on the disease site, treatment machine and clinical workflow. Errors
and inconsistencies can cause redundant work, treatment delays and potentially
treatment errors. To address these issues, an electronic checking software tool,
DosCheck was clinically implemented to check the existence of necessary
documentations and the integrity of manually-entered data. The purpose of this
software is to reduce the frequency of human errors and to improve efficiency.
METHODS: DosCheck reads data and documents from 1) TMS, 2) Pinnacle TPS, and 3)
DICOM plan files stored in a DICOM-RT PACS. It processes documents in Word and
PDF format, treatment plan data in Pinnacle native format and DICOM format, and
Mosaiq data in database records. The software cross-checks data accuracy and
consistency by following rules that are pre-defined according to the clinical
requirements and treatment sties. It interacts with dosimetrists and presents
instantaneous results via graphical user interface. RESULTS: DosCheck has been
implemented in C#. It performs a full check for a patient with 20 seconds. It has
been clinically commissioned and is used daily by all dosimetrists at our
institution. Retrospective analysis shows that DosCheck identifies 30% to 40% of
previously reported dosimetrist human errors. Additional ~30% errors are checked
by other tools that could be integrated DosCheck in the near future. CONCLUSIONS:
As an electronic data checking tool, DosCheck can obtain and process data and
documents from multiple clinical computer systems in the radiation oncology
department, and perform checks according to clinical rules. It is able to improve
the accuracy and efficiency of clinical data and document process, and therefore
to reduce any potential inconsistencies and errors.
PMID- 28520005
TI - WE-C-217BCD-07: Best in Physics (Joint Eyiaging-Therapy) - Direct Imaging of the
Uptake of Platinum Anticancer Agents Using X-Ray Stimulated Fluorescence: A Proof
Of-Concept Study.
AB - PURPOSE: Platinum-based (Pt) chemotherapy has greatly improved the initial
response rate of different cancers. However, relapse of a drug-resistant tumor
occurs with a high frequency, resulting in poor long term survival. The most
common phenotype of Pt chemoresistance is decreased Pt drug accumulation in the
tumor region due to either decreased influx or increased efflux, which is
invisible for current imaging modalities. The inability of imaging methods to
directly image the Pt drug uptake has resulted in a very unfavorable scenario for
early assessment of chemotherapeutic efficacy as well as for personalized
treatment planning. In this study, we investigated the feasibility of imaging the
uptake and retention of Pt drugs using x-ray stimulated fluorescence CT (XSF-CT).
METHODS: Pt is a high atomic number element, and it emits XSF photons when
excited by ionizing photons. Therefore, the alteration of spatial distribution
and concentration of Pt drugs in the cancer region could be monitored with XSF
CT. In this study, a polychromatic X-ray source was used to stimulate emission of
XSF photons from the Pt drugs. XSF-CT used a first-generation CT geometry. The
data were collected using a cadmium telluride detector to sort out a set of
spectra. The spectra were then used to generate sinogram. The bio distribution
and concentration of each element were reconstructed with the ML-EM algorithm.
RESULTS: The reconstructed images clearly identified the distributions of
cisplatin. A good linearity between XSF intensities and the concentrations of
cisplatin was also observed, suggesting that XSF-CT is capable of quantitative
imaging. The X-ray dose for stimulating the XSF photon was 0.25 cGy per
projection. CONCLUSIONS: XSF-CT has the potential to be a promising modality for
monitoring the intervention processes within X-ray scanners. It would afford a
powerful way to reliably modify an ineffective treatment regimen in nearly real
time. This work was supported by NIH/NCI grants (CA133474, CA153587), an NSF
grant (0854492) and a grant from the Friends for an Earlier Breast Cancer Test
Foundation.
PMID- 28520008
TI - WE-F-BRCD-01: Transitioning from 3D IMRT to 4D IMRT and Role of Image Guidance.
AB - Tumors often change shape and position over the course of Radiation Therapy. The
adaptation of the treatment to these changes, or its initial design to be robust
in light of these changes, can be referred to as 4D radiation therapy. The 4th
dimension is time and includes short term (intrafraction) and longer term (inter
fraction) changes. IMRT is an important modality for designing plans that can be
optimized for or can adapt to these changes. The combination of management of the
tumor changes and the optimization of the radiotherapy plans to deal with these
changes is 4DIMRT and will be the focus of this 2 part talk. Part 1 : Head and
Neck and Prostate treatments, focusing on adaptive therapy and image guidance.
Part 2: Thoracic treatments focusing on 4DCT, IGRT, IMRT in the lung and motion
management strategies Learning Objectives: 1. Understand currently available IGRT
and 4DCT technologies 2. Explain how these technologies can be used to improve
dose delivery precision and accuracy, in particular with dynamically changing
tumor volumes 3. Understand the challenges and strategies in clinical
implementation of IMRT in head and neck, prostate, and thorax.
PMID- 28520006
TI - WE-E-213CD-07: Deformable Registration Between CT and Truncated CBCT for Adaptive
Therapy Dose Calculation.
AB - PURPOSE: Deformable image registration (DIR) is a crucial step in adaptive
radiation therapy (ART) to deform the planning CT to the current CBCT for dose
calculation and for contour propagation. CBCT images are sometimes truncated in
the axial plane due to limited field of view (FOV). DIR between CT and truncated
CBCT often leads to unphysical results, especially in and near missing regions,
which may result in significant errors in dose calculation afterwards. The
purpose of this work is to develop and evaluate a method to improve existing DIR
algorithms to solve the truncation problem. METHODS: The radius of FOV of CBCT is
first estimated. A recently developed robust CT-CBCT DIR algorithm, called
Deformation with Intensity Simultaneously Corrected (DISC), is used for
deformation field calculation. At each iteration of DISC, the calculated
deformation vector field outside the FOV is replaced by a smooth propagation of
the deformation field inside the FOV. Six head-and-neck cancer cases and two
prostate cancer cases are used for evaluation. Dose calculation is performed to
test the impacts on the resulting dose distribution. RESULTS: In terms of DIR
accuracy, it is found that the average normalized mutual information (NMI),
normalized cross correlation (NCC) and feature similarity index (FSIM) increase
from 0.638, 0.948 and 0.917, to 0.641, 0.951 and 0.919, respectively, when
compared with DISC without propagation. In terms of dose distribution, the
relative L2 distance of dose (inside the FOV) between the ground truth and that
calculated on deformed CT with propagation reduces from 9.25%to 1.41%, compared
with those without propagation. CONCLUSIONS: We have developed a deformation
field propagation method for DIR to register the planning CT and the CBCT image
with small FOV. Tests on head-and-neck and prostate cancer cases have
demonstrated that our algorithm can generate more accurate registration results
for dose calculation. This work is supported in part by the University of
California Lab Fees Research Program, the Master Research Agreement from Varian
Medical Systems, Inc., and the grants from the National Natural Science
Foundation of China (No.30970866).
PMID- 28520009
TI - WE-E-BRB-03: Development of a Deformable Dosimetric Phantom for Verification of
4D Dose Calculation Algorithms.
AB - PURPOSE: To develop a deformable lung phantom to verify voxel mapping and dose
accumulation in 4D dose calculation algorithms used under different scenarios of
tissue compression. METHODS: The phantom consists primarily of a heterogeneous
sponge with an embedded tissue-equivalent tumor. The sponge is wrapped in a latex
balloon housed in a Lucite cylinder. The balloon is attached to a piston that
compresses the sponge to mimic the human diaphragm. The phantom was programmed to
simulate different breathing patterns. Radiochromic films and TLD were embedded
in the sponge for 4D dosimetry algorithm verification. 37 anatomical landmarks
were manually tracked to verify voxel mappings for four deformable image
registration (DIR) algorithms: in-house developed Demons and finite element model
algorithms, and two B-Spline based Velocity AI registration algorithms performed
between end-inhale and end-exhale. A 6MV photon beam was simulated with
BEAMnrc/DOSXYZnrc on the end-inhale image with the dose mapped to the end-exhale
using voxel-based linear dose mapping (LDM) and particle-based energy-mass
congruence mapping (EMCM) methods. RESULTS: The mean density of the artificial
lung was increased by 10.2% as the sponge was compressed by 2.5cm. The
reproducibility of the phantom deformation was within image resolution (1*1*3
mm3), and the accuracy of four DIR registrations of the extreme phases was within
3.0mm. With the same registration displacement vector field (DVF), EMCM and LDM
had different doses mapped to the end- exhale image. Their difference at the
center of a beam was up to 8.3% for a Demons DVF and 5.8% for a Velocity DVF. The
maximum difference between EMCM and LDM was 13.2% at beam penumbra. CONCLUSIONS:
The developed deformable dosimetric phantom readily demonstrated variations among
different dose addition and image registration algorithms, and is appropriate to
serve as a QA tool for verification of 4D dose calculation algorithms. The
research was supported by NIH/NCI R01CA140341.
PMID- 28520010
TI - WE-E-BRA-03: MR Functional Imaging to Guide Radiotherapy: Opportunities and
Challenges in the Clinic.
AB - : Human tumors are characterized by an abnormal vascular network that develops
because of unregulated angiogenesis. This contributes to abnormalities of the
tumor microenvironment like hypoxia, acidosis and high interstitial fluid
pressure that influence treatment response and patient survival. There is an
important clinical need to develop new minimally invasive tools for
characterizing the tumor microenvironment at diagnosis, and monitoring changes
during treatment with radiotherapy, chemotherapy or new biologically targeted
drugs. MR-based imaging approaches offer exciting possibilities that have yet to
be fully exploited. Dynamic contrast enhanced (DCE) MR allows the functional
characteristics of the tumor vasculature to be interrogated serially over time.
Studies in human cancers have shown substantial differences in DCE MR parameters
between tumor and normal muscle in keeping with higher blood flow and vascular
permeability. DCE MR has been shown to correlate with response to radiotherapy or
drugs that specifically target the tumor vasculature. However, despite important
advances, MR functional imaging has not been adopted in routine clinical
practice, in part because of a lack of consensus on optimal imaging techniques,
analysis methods and reporting metrics. Further refinement and standardization is
required founded on interdisciplinary collaboration among clinicians, medical
imagers, biologists, physicists and mathematicians to make these techniques
robust and clinically applicable. LEARNING OBJECTIVES: 1. Discuss the clinical
use of MR functional imaging in patients receiving radiotherapy and the
challenges to wide-spread clinical utilization. 2. Discuss the value of MR
functional imaging as a predictor of clinical outcome in patients receiving
radiotherapy, and a means of monitoring biologic response over a course of
fractionated treatment. 3. Understand the role of MR functional imaging in the
evaluation of new treatment strategies comprised of radiotherapy and drugs that
specifically target the tumor vasculature.
PMID- 28520003
TI - WE-E-213AB-01: Medical Physics Challenges for Implementation of New Technologies
in External Beam Radiotherapy.
AB - : The AAPM has signed two formal Educational Exchange Agreements with the Spanish
(SEFM) and the Russian (AMPR) medical physics societies. While the primary
purpose of the Agreements is to provide educational opportunities for young
medical physicists, the Agreements also contemplate holding joint sessions at
scientific congresses. The purpose of this professional AAPM/SEFM/AMPR Joint
Symposium is to explore the challenges that medical physicists in the three
countries face when new external beam radiotherapy technologies are introduced in
their facilities and to suggest potential solutions to limitations in testing
equipment and lack of familiarity with protocols. Speakers from the three
societies will present reviews of the technical aspects of IMRT, Arc EVIRT
(IMAT/VMAT/Rapid Arc), SRS/SRBT, and IGRT/Adaptive radiotherapy, and will
describe the status of these technologies in their countries, including the
challenges found in tasks such as developing anatomical and biological dose
optimization techniques and implementing QA management, risk assessment and
patient safety programs. The SEFM will offer AAPM and AMPR members the
possibility to participate in collaborative proposals for future research bids in
UE and USA based on an ongoing Spanish project for adaptive radiotherapy using
functional imaging. A targeted discussion will debate three propositions: the
cost/benefit ratio of IGRT, whether IMRT requires IGRT, and the use of non
ionizing radiation technologies for realtime monitoring of prostate IGRT. For
these debates, each society has designated one speaker to present and defend
either "For" or "Against" the proposition, followed by discussion by all
participants. The Symposium presentations and the country-tailored
recommendations drawn will be made available to each society for inclusion in
their websites. The WGNIMP, the AAPM Work Group charged with executing the
AAPM/SEFM and AAPM/AMPR Agreements, will follow up on the commitments made by the
AAPM.Di Yan's research on adaptive radiotherapy has been financially supported
by: 1) NIH Research Grants, 2) Elekta Research Grants 3) Philips Research
GrantConflicts of interest for Cedric X Yu: 1) Board Member of Prowess, Inc., 2)
Shareholder of Xcision Medical Systems, LLC, 3) Inventor on patents licensed by
Varian Medical Systems, Inc. LEARNING OBJECTIVES: 1. Describe fundamental aspects
for four advanced radiotherapy techniques: IMRT, IGRT, SBRT, and adaptive
radiotherapy. 2. Review technical and professional challenges for implementation
of advanced techniques as a function of resources and capabilities available
within each scientific society: AAPM, SEFM, and AMPR. 3. Discuss and plan a
proposal for an international trial on IMRT/IGRT based on functional imaging. 4.
Debate important implementation aspects of IMRT and IGRT according to country
specific resources.
PMID- 28520011
TI - WE-C-217BCD-11: Coupled Radiative and Optical Geant4 Simulation of MV EPIDs Based
on Thick Pixelated Scintillating Crystals.
AB - PURPOSE: One way to greatly reduce the incidence of metal artifacts produced in
kilovoltage (kV) CT images is by using megavoltage (MV) photons that penetrate
high-Z objects, thus providing a measurable signal. For do se-efficient imaging,
a high detective quantum efficiency (DQE) MV detector is desired. This study
validates the coupled radiation and optical Geant4 simulation results against
experimental data from various prototype pixelated scintillator MV detectors and
determines the essential optical parameters which control the detector
performance. METHODS: Experimental data obtained with a 6MV radiation source from
8 different detectors was considered. The detectors used CsI, CdW and BGO as
scintillating crystals and polystyrene septal wall material. Accurate Geant4
models of the detectors were implemented and coupled radiation and optical
simulations were performed. The unknown optical properties of the models were
determined by minimizing the difference between the modulation transfer functions
(MTF) of the simulated data obtained with the slanted slit technique and the
experimental MTFs. With the set of optical properties fixed, further simulation
validation was performed against the experimental normalized noise power spectrum
(NNPS(f)) and the experimental DQE(f) curves for each detector. All the
simulations were performed on a computer cluster deployed on the Amazon EC2
platform. RESULTS: The optimal values for the free optical parameters are 10%,
95% and 90% for the top surface reflectivity, the crystal-sept a surface
reflectivity, and the Lambertian component contribution to the reflected beam
from the crystal-septa interface respectively. The absolute difference between
experimental and simulated data was below 10% for all the data sets. CONCLUSIONS:
To our knowledge this study is the first to present a full optical and radiative
DQE(f) model using Geant4 that shows an excellent match with experimental data.
The model indicates that improved performance can be obtained using more specular
septa which are optically opaque. Support: NIH-T32-CA09695, NIH-1R01CA138426 NIH
T32-CA09695, NIH R01- CA138426, Several authors work for Varian Medical Systems.
PMID- 28520012
TI - WE-E-213CD-11: A New Automatically Generated Metric for Evaluating the Spatial
Precision of Deformable Image Registrations: The Distance Discordance Metric.
AB - PURPOSE: We propose a new metric called Distance Discordance (DD), which is
defined as the distance between two anatomic points from two moving images, which
are co-located on some reference image, when deformed onto another reference
image. METHODS: To demonstrate the concept of DD, we created a reference software
phantom which contains two objects. The first object (1) consists of a hollow box
with a fixed size core and variable wall thickness. The second object (2)
consists of a solid box of fixed size and arbitrary location. 7 different
variations of the fixed phantom were created. Each phantom was deformed onto
every other phantom using two B-Spline DIR algorithms available in Elastix and
Plastimatch. Voxels were sampled from the reference phantom [1], which were also
deformed from moving phantoms [2...6], and we find the differences in their
corresponding location on phantom [7]. Each voxel results in a distribution of DD
values, which we call distance discordance histogram (DDH). We also demonstrate
this concept in 8 Head & Neck patients. RESULTS: The two image registration
algorithms produced two different DD results for the same phantom image set. The
mean values of the DDH were slightly lower for Elastix (0-1.28 cm) as compared to
the values produced by Plastimatch (0-1.43 cm). The combined DDH for the H&N
patients followed a lognormal distribution with a mean of 0.45 cm and std.
deviation of 0.42 cm. CONCLUSIONS: The proposed distance discordance (DD) metric
is an easily interpretable, quantitative tool that can be used to evaluate the
effect of inter-patient variability on the goodness of the registration in
different parts of the patient anatomy. Therefore, it can be utilized to exclude
certain images based on their DDH characteristics. In addition, this metric does
not rely on 'ground truth' or the presence of contoured structures. Partially
supported by NIH grant R01 CA85181.
PMID- 28520013
TI - WE-E-217BCD-01: Digital Breast Tomosynthesis: Basic Principles and the QMP's
Role.
AB - : Digital breast tomosynthesis is a form of limited angle tomography, in which
section (slice) images are produced from a series of discrete projection images
acquired at different angles. Tomosynthesis can be useful in breast imaging by
providing potentially better visibility of lesions over conventional mammography,
especially in patients with dense breasts. This talk will cover the various
physics aspects of DBT, including reconstruction algorithms, the importance of
deblurring, and optimizing image acquisition parameters. Remaining important
research questions in DBT will be presented and discussed. The presentation will
also discuss MQSA Certificate extension process for currently approved digital
breast tomosynthesis (DBT) systems. Training requirements, manufacturer required
tests for Mammography Equipment Evaluation (MEE) as acceptance tests, and phantom
imaging for the purpose of approval of certificate extension will be described.
The talk will emphasize the specific tests where special attention must be given
and will discuss how the techs should be advised to perform these tests. LEARNING
OBJECTIVES: 1. To understand the fundamentals of tomosynthesis reconstruction,
including deblurring, algorithm choice, and optimization 2. To understand FDA's
certificate extension process for DBT 3. To understand the requirements for MEE
4. To understand the required AEC tracking data Research sponsored in part by
NIH, Siemens, and GE Healthcare.
PMID- 28520014
TI - WE-E-BRB-07: Direct 3D Fluence Calculation from Machine Beam Parameters for VMAT
Delivery Verification.
AB - PURPOSE: MLC dynamic log files have been clinically used for quality assurance
for years. The logged machine parameters and the derived beam 2D fluence maps can
be compared to the ones obtained in the treatment plans in order to evaluate the
accuracy and consistency of IMRT beam deliveries. In this study, we propose a
computationally efficient method, called Direct 3D Fluence Calculation or D3DFC,
to extend 2D fluence map derivation to 3D fluence volume computation. The aim is
to extend dynalog-based QA from fixed-gantry IMRT to rotational-gantry VMAT.
METHODS: D3DFC calculates the 3D volume of photon fluence distribution directly
from the machine parameters (gantry angles, jaw positions, MLC positions,
collimator rotation angle, MU) contained in the dynamic log files or DICOM plans,
without converting to 2D fluence maps per gantry angle in order to allow higher
computation speed and accuracy. For testing, results were verified with film-in
air measurements. 3D fluence volumes computed from VMAT delivery records (with
artificially introduced delivery errors) are compared to ones computed from the
treatment plans to determine if these delivery errors can be identified. RESULTS:
D3DFC is implemented in MATLAB and supports the DICOM plans, Varian MLC dynamic
logs and Varian Truebeam machine logs. Computation takes 10 to 20 seconds for a
single-arc VMAT plan or delivery records. The results showed that 1 mm MLC errors
can be clearly detected using delivery-to-plan fluence volume comparison.
CONCLUSIONS: Direct computation from machine parameters allows higher computation
speed and accuracy. These advantages are useful for beam delivery verification
purposes for which (slower) full patient CT based dose computation is less
necessary. The calculated 3D photon fluence volume is useful to detect and
visually present the VMAT delivery discrepancies.
PMID- 28520015
TI - WE-E-211-01: Medical Physics in Federal and State Governments.
AB - : In 2010, FDA's Center for Devices and Radiological Health (CDRH) launched an
"Initiative to Reduce Unnecessary Radiation Exposure from Medical Imaging" and
held a public meeting on "Device Improvements to Reduce Unnecessary Radiation
Exposure from Medical Imaging" March 30- 31, 2010). In follow-up, FDA is pursuing
efforts using its regulatory authority as it applies to imaging equipment and
manufacturers and also partnering with professional organizations such as AAPM,
industry and other governmental agencies to incorporate radiation protection
principles into facility quality assurance, personnel credentialing, and training
requirements.The current U.S. Federal guidance on medical x-rays was published in
1976 and addresses film imaging for radiographie and dental modalities. The
Medical Workgroup of the Interagency Steering Committee on Radiation Standards
(ISCORS) has modernized that document to address both diagnostic and
interventional approaches, film and digital imaging, and the broad range of
modalities that include radiography, computed tomography, interventional
fluoroscopy, dentistry, bone densitometry, and veterinary practice. The current
scope and status of the document will be presented.The Military Health System is
committed to providing state-of- the-art care to its beneficiaries; both at home
and abroad. Personnel constraints and the continuing wars oversees have created
obstacles to this objective. In the past decade, tremendous advances have
occurred in Electronic Health Records (EHR) and Teleradiology. Military Radiology
seeks to leverage these advances as a means of surmounting many of the challenges
it faces. In this talk, the current status of DoD teleradiology and EHR will be
presented. LEARNING OBJECTIVES: 1. To provide a venue in which physicists working
in the public sector can interface and discuss specific issues related to
supporting the federal and state governments 2. To provide a venue for medical
physicists to voice specific concerns with federal/state programs where medical
physics should be involved in and/or more effective. 3. To educate audience on
federal or state new or updated guidelines.
PMID- 28520016
TI - WE-E-BRB-09: A GPU-Based Monte Carlo QA Tool for IMRT and VMAT.
AB - PURPOSE: To develop a GPU-based Monte Carlo (MC) 3D dosimetry quality assurance
(QA) tool employing patient geometry and actual delivery information. METHODS:
First, we generate fluence maps at all beam angles from the initial treatment
plan. A GPU-based MC dose engine, gDPM, is employed for the secondary dose
calculation (SDC) on patient CT. This SDC is used to verify the TPS plan dose
(PD) accuracy. Before the 1st treatment fraction, we deliver the treatment plan
on a Linac without any phantom setup to obtain machine log files. With the log
files, we extract actually delivered fluence maps at all beam angles and perform
delivered dose calculation (DDC) using gDPM. The difference between DDC and SDC
indicates possible errors in data transferring and machine delivery. Lastly, the
comparison between DDC and PD shows the accumulative errors from all the possible
sources. Moreover, a web application for this QA tool is developed for clinical
use. We have tested this QA tool on 6 patients, 4 VMAT and 2 IMRT patients. We
reported mean gamma values and passing rates inside the 20% isodose line; DVH
plot and dose difference matrix are also documented. RESULTS: For all six
patients, the gamma passing rates within the 20% isodose line for SDC, DDC and PD
comparisons are all higher than 95%. In the DVH plot, the three dose
distributions were found to be very close. A typical IMRT or VMAT case takes less
than one minute to run the whole QA tool. CONCLUSIONS: We have developed a GPU
based MC QA tool which can be used for efficient and easy IMRT and VMAT QA.
PMID- 28520017
TI - WE-C-217BCD-06: In Vivo Targeting and Imaging of Tumor Vasculature with
Radiolabeled, Antibody-Conjugated Nano-Graphene.
AB - PURPOSE: Our goal was to explore nano-graphene for in vivo tumor targeting and
quantitatively evaluate the pharmacokinetics and tumor targeting efficacy through
PET imaging, using 6 4 Cu and 66 Ga as the radiolabel. METHODS: Nano-graphene
oxide (GO) sheets, with amino group- terminated PEG chains (10 kDa) covalently
attached, were conjugated to NOTA (l,4,7-triazacyclononane-l,4,7-triacetic acid,
a suitable chelator for 6 4 Cu and 6 6 Ga) and TRC105 (a mAb that binds to CD
105, overexpressed on neovasculature). FACS analyses, size measurements, and
serum stability studies were performed to characterize the GO conjugates before
in vivo investigation (PET, bio distribution, blocking studies, etc.) in 4T1
murine breast tumor-bearing mice. Findings from imaging studies were then
validated by histology. RESULTS: TRC105-conjugated GO, 20-30 nm in diameter, was
specific for CD105 with little non-specific binding. Both 64 Cu- and 66 Ga-
labled GO conjugates had excellent stability in mouse serum. Clearance of the GO
conjugates in mice was via the hepatobiliary pathway. v Cu/6 6 Ga-NOTA-GO-TRC105
accumulated rapidly in the 4T1 tumor and tumor uptake remained stable over time
(3.8+/-0.4, 4.5+/-0.4, 5.8+/-0.3, and 4.5+/-0.4 %ID/g at 0.5, 3, 7, and 24 h p.i.
for66 Ga; 5.8+/-0.6, 5.3+/-0.6, 4.0+/-0.4, and3.4+/-0.1 %ID/g at 0.5, 3,24, and
48 h p.i. for 6 4 Cu; n = 4). Blocking studies confirmed CD105 specificity of 6 4
Cu/6 6 Ga-NOTA- GOTRC105, which was corroborated by bio distribution studies.
Furthermore, microscopy examination of GO in light view mode and
immunofluorescence staining revealed that targeting of NOTA-GO-TRC105 is tumor
vasculature CD105 specific with little extravasation. CONCLUSIONS: For the first
time, we demonstrated that GO can be specifically directed to the tumor
neovasculature in vivo through targeting of CD105, a marker of tumor
angiogenesis. The versatile chemistry of graphene-based nanomaterials makes them
suitable nanoplatforms for future biomedical research, such as cancer
theranostics.
PMID- 28520018
TI - WE-E-213CD-06: A Locally Adaptive, Intensity-Based Label Fusion Method for Multi-
Atlas Auto-Segmentation.
AB - PURPOSE: Atlas-based auto-segmentation (ABAS) has emerged as a very useful
contouring tool for radiotherapy planning. Higher accuracy of ABAS typically
requires the use of multiple atlases, for which the final label fusion step is a
key design component. This work presents a novel locally adaptive, intensity
based label fusion approach for multi-atlas ABAS, and compares its performance
against the commonly used STAPLE method. METHODS: The label fusion method derives
the final structure label for a novel patient image as a weighted average of
several warped atlas label maps, where the atlas warping is achieved through
deformable atlas registration. Instead of assigning a constant global weighting
factor for each atlas and for each structure, adaptive weights are computed at
each image location based on the local correlation coefficients (LCC) computed
between the patient image and each warped atlas image. To compensate for
registration errors, neighboring atlas labels within a small distance from the
center point are also considered in the fusion computation, but only the first k
(typically 25) neighbors with the largest LCC are included to get better
accuracy. The method was evaluated using ten manually contoured H&N patient
images with a leave-one-out validation strategy. Performances of the newly
proposed method and the classical STAPLE method are compared for 7 structures
including the mandible, the parotids (left and right), the sub- mandibular glands
(left and right), the brainstem, and the spinal cord. RESULTS: The proposed
intensity-based label fusion method significantly outperforms the STAPLE method
for all structures considered. The improvement of the mean Dice value ranges from
1.5%for the right parotid to 9% for the right sub-mandibular gland. CONCLUSIONS:
The locally adaptive, intensity-based label fusion provides a superior accuracy
compared to the STAPLE method, which helps boost the performance of ABAS methods
and make them more usefulness in practice. The author is a current employee of
Elekta Inc.
PMID- 28520019
TI - WE-C-218-01: Ultrasound Contrast Agents.
AB - : Medical ultrasound has long been used in clinical applications both as a
primary modality and as a supplement to other diagnostic procedures. The basis
for ultrasound imaging is the transmission of high frequency (megaHertz) sound
waves that propagate through tissue. These sound waves backscatter from the
interfaces between tissue components with different acoustic properties and are
detected by the imaging system, allowing the creation of images based on tissue
characteristics and spatial location. Thus, traditional ultrasound has focused
primarily on the imaging of anatomical structures and analysis of blood flow in
large vessels. Unfortunately, blood is a weak scatterer, which can make vascular
diagnostic applications (example: echocardiography) challenging especially with
larger patients. Contrast agents help to improve on this shortcoming by enhancing
the visualization of blood flow, thus improving the quality of diagnostics. The
use of contrast agents for ultrasound was first reported in 1968 when Gramiak and
Shah discovered that there was an increased backscatter of ultrasound caused by
injected microbubbles. This is because the mismatch in acoustic impedance (a
function of an object's density and compressibility) between the microbubble gas
core and blood (or tissue) is several orders of magnitude, which results in
substantially higher scattering from a bubble than an equivalent volume of tissue
or blood. Additionally, microbubbles oscillate in response to an ultrasound
field, and respond non-linearly to acoustic pulses even at low energies, unlike
tissue. The non-linear property of microbubbles in an ultrasound field allows for
the use of various pulsing and signal processing strategies to detect the
backscattered signal from contrast agents and segment it from tissue, thus
providing a high contrast-to- noise ratio. Due to these unique acoustic
properties, a clinical ultrasound system can detect even single microbubble
contrast agents, providing exquisite sensitivity and the ability to perform
advanced diagnostic procedures. Over the last several decades, ultrasound
contrast agents have been improved for enhanced stability and increased
persistence times. Although preclinical studies as well as clinical use in Europe
and Asia strongly suggest that the use of contrast ultrasound can substantially
improve diagnostic capabilities in both cardiology and radiology applications,
contrast use in the US is still very limited. Obstacles to the widespread use of
microbubbles include safety concerns, the need for optimization of approaches for
contrast use, and general understanding of their potential by physicians. This
course covers the basic principles of contrast agents used in ultrasound imaging
including their stability, shell properties and their behavior within an acoustic
field. In addition, we will cover many new techniques that are being evaluated in
preclinical studies including: p er fus ion-based techniques, molecular imaging,
gene therapy, drug delivery, and acoustic angiography. Finally, basic safety
concerns and biological effects will be reviewed. LEARNING OBJECTIVES: 1.
Understand the basic principles of ultrasound contrast agents a. What are
microbubble contrast agents? b. Properties of microbubbles c. Safety concerns and
biological effects 2. Understand basic contrast imaging techniques a. Harmonic
and suharmonic imaging techniques b. Pulse inversion techniques 3. Understand the
use of contrast agents in various vascular applications a. Traditional methods
(Cardiovascular, Abdominal) b. Advanced perfusion imaging techniques 4.
Understand the role of contrast agents in preclinical applications a. Ultrasound
molecular imaging b. Gene therapy c. Drug delivery d. Acoustic angiography.
PMID- 28520020
TI - WE-F-211-01: The Evolving Landscape of Scientific Publishing.
AB - : The dissemination of scientific advances has changed little since the first
peer-reviewed journal was published in 1665 - that is, until this past decade.
The print journal, delivered by mail and stored on office shelves and in library
reading rooms around the world, has been transformed by immediate, on-demand
access to scientific discovery in electronic form. At the same time, the
producers and consumers of that scientific content have greatly increased in
number, and the balance between supply and demand has required innovations in the
world of scientific publishing. In light of technological advances and societal
expectations, the dissemination of scientific knowledge has assumed a new form,
one that is dynamic and rapidly changing. The academic medical physicist must
understand this evolution to ensure that appropriate decisions are made with
regard to journal submission strategies and that relevant information on new
findings is obtained in a timely manner. Medical Physics is adapting to these
changes in substantive ways. This new scientific publishing landscape has
implications for subscription models, targeted access through semantic
enrichment, user interactivity with content, customized content delivery, and
advertising opportunities. Many organizations, including the AAPM, depend on
scientific publishing as a significant source of revenue, but web-based delivery
raises the expectation that access should be free and threatens this model. The
purpose of this symposium is to explore the factors that have contributed to the
current state of scientific publishing, to anticipate future directions in this
arena, and to convey how medical physicists may benefit from the expanded
opportunities, both as authors and as readers. LEARNING OBJECTIVES: 1. To
appreciate the importance of scientific and clinical practice communication for
the advancement of the medical physics field 2. To understand the roles of the
Editorial Board and the Journal Business Management Committee in the promotion
and advancement of Medical Physics 3. To explore technology-driven content
delivery mechanisms and their role in facilitating content access and driving
content usage 4. To understand the potential benefits and pitfalls of various
economic and editorial models of scientific publications and the recent shifts
away from the traditional role of libraries.
PMID- 28520021
TI - WE-E-BRB-02: Evaluation of Analytical Proton Dose Predictions with a Lung-Like
Plastic Phantom.
AB - PURPOSE: Former studies have shown that in homogeneities in the path of
therapeutic proton beams can lead to a degradation of the distal edge of the
Bragg peak. These studies mostly investigated bone-air interfaces. This study
focuses on distal edge degradation caused by finely structured soft tissue - air
interfaces, which can be found in lung tissue. METHODS: A randomly filled
voxelized lung-like phantom was designed and produced using rapid prototyping
methods. The results of transmission measurements on this phantom were used to
validate Monte Carlo (MC) calculations, which were then used as gold standard to
calculate doses in several lung equivalent geometries (phantoms). The results
were compared to the results of analytical dose calculation engines. RESULTS:
Transmission measurements showed that the distal falloff width (from 90 % of the
peak dose to 10 %) in water increased from 3.32 mm by 117 % to 7.19 mm for an
initial proton energy of 140 MeV, and from 5.95 mm to 9.03 mm (52 %) for 200 MeV.
The peak dose in the degraded beam was only 70 % (for 140 MeV) and 84 % (for 200
MeV) of the value observed in non-degraded beams. These findings were in contrast
to the results obtained with analytical dose computation engines, but are in
agreement with MC calculations. CONCLUSIONS: If not predicted correctly, Distal
Edge Degradation in lung cancer therapy can lead to severe under-dosage of the
target region and unwanted dose in organs at risk distal to the Bragg peak.
Therefore clinically used dose calculation algorithms have to be extended to take
lateral in homogeneities into account.
PMID- 28520022
TI - WE-E-BRA-02: Optimization of Functional MRI Techniques for Assessment of Tumor
and Normal Tissue Response to RT.
AB - : The advantages of physiological and functional MRI for radiation treatment
assessment of tumor response and normal tissue damage for adaptive RT as well as
for boost target definition are well recognized. However, several limitations of
functional MRI have hindered its wide application in radiation therapy, including
concerns about optimal pulse sequence parameters, high resolution volumetric
acquisition, acquisition speed, motion-sensitivity, reproducibility, and image
processing. Many of these shortcomings have been overcome or will be overcome by
standardization of image acquisition and quantification. It is also important to
understand sensitivity and specificity of these imaging techniques for particular
clinical questions. This lecture will provide an overview on these techniques and
issues. Examples of applying these techniques to liver and prostate will be
given. LEARNING OBJECTIVES: 1. Understand new MRI technologies that are relevant
to radiation treatment assessment; 2. Understand the influence of imaging
parameters on image quality and contrast; 3. Understand image processing
techniques for derived quantitative parameters; 4. Understand clinical
applications and limitations. Author's work is supported in part by NIH P01
CA59827, NCI RO1 CA132834, and RO1 NS064973. 3959.
PMID- 28520023
TI - WE-C-217BCD-10: Development of High Performance PET for Animal Imaging and
Therapy Applications.
AB - PURPOSE: A prototype small animal PET is developed with several novel
technologies to measure 3D gamma-interaction positions and to substantially
improve imaging performance. METHODS: Each new detector has an 8*8 array of
1.95*1.95*30 mm3 LYSO scintillators, with each end optically connected to a solid
state photo multiplier (SSPM) array through a light guide. This dual-ended
readout enables the depth-of-interaction (DOI) measurement. Each SSPM array has
16 SSPMs arranged in a 4*4 matrix. Each SSPM has active area about 3*3 mm2, with
its output read by an ASIC electronics that directly converts analog signals to
digital timing pulses which encode the interaction information for energy,
timing, crystal of interaction, and DOI calculations. These digital pulses are
transferred to and decoded by FPGA-based TDC for coincident event selection and
data acquisition. This independent readout of each SSPM and parallel signal
process significantly improve signal-to-noise ratio and permit applying flexible
data processing algorithms. The current prototype system consists of two rotating
detector panels on a portable gantry, with 4 detectors linearly packed together
in each panel to provide ~16 mm axial and variable trans- axial FOV with
adjustable panel-to-panel distance. List-mode OSEM-based image reconstruction
with resolution modeling was implemented. Both Na- 22 point source and phantom
were used to evaluate the system performance. RESULTS: The measured energy,
timing, spatial and DOI resolutions for each crystal were around 16%, 2.6 ns, 2.0
mm and 5.0 mm, respectively. The measured spatial resolutions with DOI were ~1.7
mm across the entire FOV in all direction, while those without DOI were much
worse and non-uniform across the FOV, in the range predominately around 3.0 to
4.0 mm. In addition, images from a F-18 hot-rod phantom with DOI show
significantly improved quality compared to those without DOI. CONCLUSIONS: DOI-
measurable PET shows substantially improved image performance for a compact
system. National Institute of Health. University of Texas MD Anderson Cancer
Center.
PMID- 28520024
TI - WE-E-213CD-10: A Robust 2D/3D Image Registration System for Pediatric Patient
Setup in External Beam Radiotherapy.
AB - PURPOSE: To develop a neural network based registration quality evaluator (RQE)
that can improve the 2D/3D image registration robustness for pediatric patient
setup in external beam radiotherapy. METHODS: X-ray setup images of six pediatric
patients with brain tumors received proton therapies were retrospectively
registered with their treatment planning computed tomography (CT) images. A
neural network based pattern classifier was used as an RQE to classify 2D/3D
rigid registration solutions as successful or unsuccessful based on features of
the similarity value surfaces near the point-of-solution. The supervised training
and test datasets were generated by rigidly registering a pair of orthogonal
daily setup x-ray images to the treatment planning CTs. The best solution for
each registration task was selected from 50 optimizing attempts that differed
only by the initial transformation parameters. The distance from each individual
solution to the best solution in the normalized parametrical space was compared
to a user- defined error threshold to determine whether that solution was
successful. The supervised training was then used to train the RQE. The
performance of the RQE was evaluated using the test dataset that consisted of
registration results that were not used in training. RESULTS: With the optimized
sampling step size, i.e., 5 mm, in the feature space, the RQE has the sensitivity
and the specificity in the ranges of 0.865-0.964 and 0.797-0.990, respectively,
when it was used to detect the registration error with the mean voxel
displacement (MVD) greater than 1 mm. CONCLUSIONS: The proposed RQE can
potentially be used in a 2D/3D rigid image registration system to improve its
robustness by rejecting unsuccessful registration solutions. The RQE is non
patient specific and needs only to be trained once for each treatment site. The
implementation the RQE in a 2D/3D registration system results only 10% to 20%
increase of the overall computation time. The authors have no conflict of
interest to disclose.
PMID- 28520084
TI - Renal and hematologic side effects of long-term intravenous immunoglobulin
therapy in patients with neurologic disorders.
AB - INTRODUCTION: For patients receiving intravenous immunoglobulin (IVIg), renal and
hemolytic side effects are well recognized. However, there are very few data on
the effects of chronic IVIg therapy. METHODS: We retrospectively analyzed
laboratory data on 166 patients who received IVIg for 12 months with a dose range
of 0.441-2.58 g/kg/month, measuring changes in hematocrit and glomerular
filtration (GFR) rates at 6 and 12 months. RESULTS: Of the 2,232 infusions, there
were no incidents of clinical hemolysis. However, after 12 months of treatment,
21% of patients had a >=3-g/dl decline in hematocrit and 10% had a >=20% decline
in GFR. DISCUSSION: No clinically significant hemolysis was observed in patients
receiving chronic IVIg therapy. However, a significant number of patients had a
decline in hematocrit and/or GFR while on therapy. This emphasizes the need for
observation of hematologic and renal function in patients treated with chronic
IVIg. Muscle Nerve 56: 1173-1176, 2017.
PMID- 28520085
TI - Assessment of the Relationship between Body Mass Index and Incidence of Venous
Thromboembolism in Hospitalized Overweight and Obese Patients.
AB - STUDY OBJECTIVE: To assess whether a positive linear association exists between
body mass index (BMI) and incidence of venous thromboembolism (VTE) in overweight
and obese hospitalized patients. DESIGN: Single-center retrospective
observational cohort study. SETTING: Large academic tertiary care medical center.
PATIENTS: A total of 1452 adults hospitalized between January 1, 2013, and
December 31, 2014, who weighed more than 100 kg and had a BMI of 25 kg/m2 or
greater on admission, and received heparin subcutaneously for VTE prophylaxis.
Patients were categorized into four subgroups based on World Health Organization
BMI classification: overweight (141 patients), obese class I (305 patients),
obese class II (324 patients), and obese class III (682 patients). MEASUREMENTS
AND MAIN RESULTS: The primary outcome was occurrence of VTE in each subgroup; all
cause mortality and length of hospital stay were secondary outcomes. A linear
trend test did not show an association between occurrence of VTE and BMI of 25
kg/m2 or greater. VTE occurred in 7 (5%) of 141 patients in the overweight group,
5 (2%) of 305 in the obese class I group, 8 (3%) of 324 in the class II group,
and 18 (3%) of 682 in the class III group (p=0.573). In addition, no linear
association was noted between all-cause mortality or length of hospital stay and
BMI of 25 kg/m2 or greater. Overall mortality was 10% (146/1452 patients). Ten
deaths (7%) occurred in the overweight group, 45 (15%) in the obese class I
group, 38 (12%) in the obese class II group, and 53 (8%) in the obese class III
group (p=0.067). The median length of hospital stay was 5 days (interquartile
range 3-9, p=0.122) for all patients. CONCLUSION: In overweight and obese
hospitalized patients who weighed more than 100 kg and had a BMI of 25 kg/m2 or
greater, the incidence of VTE did not increase incrementally with increasing
severity of obesity.
PMID- 28520086
TI - Activated FGFR3 prevents subchondral bone sclerosis during the development of
osteoarthritis in transgenic mice with achondroplasia.
AB - The purpose of this study is to investigate the morphometric changes of the
subchondral bone during the development of osteoarthritis (OA) in transgenic mice
with achondroplasia (Fgfr3ach ) carrying a heterozygous gain-of-function mutation
in Fgfr3. Two OA models (spontaneously developed with age: The aging model, and
surgically induced by destabilization of the medial meniscus: The DMM model) were
established. Articular cartilage, epiphysis, and metaphysis of the knee joint
were histologically and morphometrically compared between wild-type mice, and
Fgfr3ach mice in both OA models. Articular cartilage degeneration was scored
according to the Osteoarthritis Research Society International (OARSI) scoring
system. Several morphometric parameters including bone mineral density (BMD),
bone volume/tissue volume (BV/TV), trabecular bone thickness (Tb.Th), and
subchondral bone thickness in the medial tibial plateau (MTP) (Sb.Th med) were
quantified by micro-computed tomography (CT). In the aging model, although there
were no significant differences in the OARSI score between wild-type mice and
Fgfr3ach mice, Sb.Th med and Tb.Th in the epiphysis significantly increased in
wild-type mice. In the DMM model, the OARSI score of the medial compartment was
significantly lower in Fgfr3ach mice than in wild-type mice. BMD, BV/TV, and
Tb.Th in the epiphysis increased in wild-type mice and unchanged in Fgfr3ach
mice, and the Sb.Th med was significantly larger in wild-type mice after surgery.
Subchondral sclerosis, which preceded the cartilage degeneration, was inhibited
in Fgfr3ach mice. Activated FGFR3 signaling prevented sclerotic changes of the
subchondral bone and subsequent cartilage degeneration. (c) 2017 Orthopaedic
Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:300-308,
2018.
PMID- 28520088
TI - Clathrin-mediated endocytosis is required for ANE 30-100K-induced autophagy.
AB - BACKGROUND: We identified an autophagy-inducing areca nut (AN) ingredient (AIAI)
in the 30-100 kDa fraction of AN extract (ANE 30-100K). This study was to analyze
the role of endocytosis in ANE 30-100K-induced autophagy. METHODS: We used benzyl
alcohol, dynasore, and shRNA of clathrin and dynamin to assess whether ANE 30
100K-induced cytotoxicity and accumulation of microtubule-associated protein 1
light chain 3 (LC3)-II were affected in oral (OECM-1) and esophageal (CE81T/VGH)
carcinoma cells. RESULTS: Both benzyl alcohol and dynasore effectively reduced
ANE 30-100K-induced cytotoxicity and LC3-II accumulation in OECM-1 and CE81T/VGH
cells. Downregulated protein expression of both clathrin and dynamin by their
shRNA also significantly attenuated ANE 30-100K-induced elevation of LC3-II
levels in CE81T/VGH cells. CONCLUSIONS: These results indicate that AIAI may be
engulfed by cells through clathrin-mediated endocytosis, which promotes the
execution of the following autophagy program.
PMID- 28520087
TI - Geographic variation and risk factors for systemic and limb ischemic events in
patients with symptomatic peripheral artery disease: Insights from the REACH
Registry.
AB - BACKGROUND: Patients with symptomatic peripheral artery disease (PAD) are at high
risk of ischemic events. However, data about predictors of this risk are limited.
HYPOTHESIS: We analyzed baseline characteristics and 4-year follow-up of patients
enrolled in the international REduction of Atherothrombosis for Continued Health
(REACH) Registry with symptomatic PAD and no history of stroke/transient ischemic
attack to describe annual rates of recurrent ischemic events globally and
geographically. METHODS: The primary outcome was systemic ischemic events
(composite of cardiovascular death, myocardial infarction, or stroke) at 4 years.
The secondary outcome was limb ischemic events (composite of lower limb
amputation, peripheral bypass graft, and percutaneous intervention for PAD) at 2
years. Multivariate analysis identified risk factors associated with recurrent
ischemic events. RESULTS: The primary endpoint rate reached 4.7% during the first
year and increased continuously (by 4%-5% each year) to 17.6% by year 4, driven
mainly by cardiovascular mortality (11.1% at year 4). Japan experienced lower
adjusted ischemic rates (P < 0.01) vs North America. Renal impairment (P < 0.01),
congestive heart failure (P < 0.01), history of diabetes (P < 0.01), history of
myocardial infarction (P = 0.01), vascular disease (single or poly, P < 0.01),
and older age (P < 0.01) were associated with increased risk of systemic ischemic
events, whereas statin use was associated with lower risk (P = 0.03). The limb
ischemic event rate was 5.7% at 2 years. CONCLUSIONS: Four-year systemic ischemic
risk in patients with PAD and no history of stroke or transient ischemic attack
remains high, and was mainly driven by cardiovascular mortality.
PMID- 28520089
TI - Observational study investigating tooth extraction and the shortened dental arch
approach.
AB - The shortened dental arch (SDA) provides a cost-effective dentition, considering
the population is ageing and retaining teeth for longer. The aims were to observe
the reasons and sites of tooth extraction and assess the functional dentition
over 15 years in dental practice. Subjects were recruited who required permanent
tooth extractions between 2000 and 2015. The reasons for extractions were chosen
from twelve extraction codes. Data were also collected for demographics, tooth
position, root treated teeth and functional pairs remaining. Patient-centred
factors on reasons for tooth extraction and comments on chewing ability and
aesthetics following extractions were recorded. Nine hundred and fifty-one teeth
were extracted in 900 patients. The mean age was 60 years (SD 20, SE 7, 95% CI
46, 74). Reasons for extraction were periodontal disease (n = 361, 38%),
periapical infection (n = 288, 34%) or tooth and tooth-root fractures (15%).
Extractions included 201 (21%) second molars, 179 (19%) first molars, 152 (16%)
second premolars, 95 (10%) first incisors, 86 (9%) second incisors, 76 (8%)
canines and 67 (7%) first premolars. Following extractions, median functional
pairs were 12, interquartile range (IQR) 19-7. Individuals with >=10 functional
pairs including anterior teeth (60%, n = 571) had no complaints with chewing
ability or aesthetics. They did not require additional prostheses. Periodontal
disease and periapical infection were the main causes for the extraction. First
and second molars followed by second premolars were the most commonly extracted
teeth. This study supports the SDA in creating a cost effective, functional
dentition in an aging population, provided remaining teeth and restorations are
preserved/maintained, oral health is promoted, and anterior aesthetic tooth
replacement is ensured.
PMID- 28520090
TI - Robotic ventral mesh rectopexy - a video vignette.
PMID- 28520091
TI - Selective analysis of aristolochic acid I in herbal medicines by dummy
molecularly imprinted solid-phase extraction and HPLC.
AB - In this study, surface molecularly imprinted polymers were prepared as the
selective sorbents for separation of aristolochic acid I in herbal medicine
extracts by a facile approach. A less toxic dummy template, ofloxacin, was used
to create specific molecule recognition sites for aristolochic acid I in the
synthesized polymers. The polymers were characterized by Fourier-transfer
infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis,
elemental analysis, and nitrogen adsorption-desorption test. The adsorption
capacity was calculated using adsorption kinetics, selectivity, and recycling
experiments. The obtained polymers exhibited high thermostability, fast
equilibrium time, and excellent binding ability. Subsequently, the polymers
applied as the solid-phase extraction absorbent was proposed and used for the
enrichment and analysis of aristolochic acid I in herbal plants. The result
showed that the aristolochic acid I was enriched up to 16 times after analysis by
using high-performance liquid chromatography. The good linearity for aristolochic
acid I was obtained in the range of 0.1-200 MUg/mL (R2 = 0.9987). The recovery
and precision values were obtained (64.94-77.73%, RSDs% <= 0.8%, n = 3) at three
spiked concentration levels. This work provided a promising method for selective
enrichment, extraction, and purification of aristolochic acid I from complex
herbal plants.
PMID- 28520092
TI - Mushrooms as Efficient Solar Steam-Generation Devices.
AB - Solar steam generation is emerging as a promising technology, for its potential
in harvesting solar energy for various applications such as desalination and
sterilization. Recent studies have reported a variety of artificial structures
that are designed and fabricated to improve energy conversion efficiencies by
enhancing solar absorption, heat localization, water supply, and vapor
transportation. Mushrooms, as a kind of living organism, are surprisingly found
to be efficient solar steam-generation devices for the first time. Natural and
carbonized mushrooms can achieve ~62% and ~78% conversion efficiencies under 1
sun illumination, respectively. It is found that this capability of high solar
steam generation is attributed to the unique natural structure of mushroom,
umbrella-shaped black pileus, porous context, and fibrous stipe with a small
cross section. These features not only provide efficient light absorption, water
supply, and vapor escape, but also suppress three components of heat losses at
the same time. These findings not only reveal the hidden talent of mushrooms as
low-cost materials for solar steam generation, but also provide inspiration for
the future development of high-performance solar thermal conversion devices.
PMID- 28520093
TI - Verticillium dahliae transcription factor VdFTF1 regulates the expression of
multiple secreted virulence factors and is required for full virulence in cotton.
AB - Fungal transcription factors (TFs) implicated in the regulation of virulence gene
expression have been identified in a number of plant pathogens. In Verticillium
dahliae, despite its agricultural importance, few regulators of transcription
have been characterized. In this study, a T-DNA insertion mutant with
significantly reduced virulence towards cotton was identified. The T-DNA was
traced to VdFTF1, a gene encoding a TF containing a Fungal_trans domain.
Transient expression in onion epidermal cells indicated that VdFTF1 is localized
to the nucleus. The VdFTF1-deletion strains displayed normal vegetative growth,
mycelial pigmentation and conidial morphology, but exhibited significantly
reduced virulence on cotton, suggesting that VdFTF1 is required exclusively for
pathogenesis. Comparisons of global transcription patterns of wild-type and
VdFTF1-deletion strains indicated that VdFTF1 affected the expression of 802
genes, 233 of which were associated with catalytic processes. These genes encoded
69 potentially secreted proteins, 43 of which contained a carbohydrate enzyme
domain known to participate in pathogenesis during infection of cotton. Targeted
gene deletion of one VdFTF1-regulated gene resulted in significantly impaired
vascular colonization, as measured by quantitative polymerase chain reaction, as
well as aggressiveness and symptom severity in cotton. In conclusion, VdFTF1,
which encodes a TF containing a Fungal_trans domain, regulates the gene
expression of plant cell wall degradation enzymes in V. dahliae, which are
required for full virulence on cotton.
PMID- 28520094
TI - Regulatory disorders in early childhood: Correlates in child behavior, parent
child relationship, and parental mental health.
AB - According to the guidelines published by the German Society of Child and
Adolescent Psychiatry, Psychosomatics and Psychotherapy (2007), regulatory
disorders of early childhood are characterized by a symptom triad, including (a)
behavioral symptoms such as excessive crying, sleeping, or feeding problems; (b)
a disturbed parent-child relationship; and (c) parental psychopathology. On the
basis of a clinic-referred sample of 162 children, we examined whether children
with and without regulatory symptoms differed in the quality of parent-child
relationship and parental mental health, and how often the criteria of the
symptom triad were fulfilled in the group of children with regulatory symptoms.
In addition, emotional and behavior problems were compared in children with and
without regulatory symptoms. Children with regulatory symptoms and children with
other psychiatric symptoms did not differ with respect to child-parent
relationship quality. However, parents of children with regulatory symptoms
scored higher on the Symptom Checklist 90 Items-Revised (G.H. Franke, 2002) than
did the other parents. On the Child Behavior Checklist (T.M. Achenbach & L.A.
Rescorla, 2000), children with regulatory symptoms tended to show more somatic
problems, but they showed significantly less withdrawn behavior than did the
other children. Of the 67 children with regulatory symptoms, only 11 (16.4%)
fulfilled all three criteria of a regulatory disorder.
PMID- 28520095
TI - A quantitative psychometric evaluation of an intervention for poor dietary
variety in children with a feeding problem of clinical significance.
AB - Few studies have been published that offer a quantitative evaluation of
interventions for feeding problems of clinical significance. Twenty-four children
referred to the service for clinically significant feeding problems were
administered the Behavioral Pediatric Feeding Assessment Scale (BPFAS; W. Crist &
A. Napier-Phillips, 2001) and the Child Feeding Assessment Questionnaire (CFAQ;
G. Harris & I.W. Booth, 1992) before and after a duel targeted 16-week
therapeutic intervention to improve dietary variety. Dietary variety was assessed
through a food diary where only items that were accepted on more than one
occasion were deemed to be part of the child's habitual diet. Results indicated
that all subscales of the BPFAS and the CFAQ were responsive to the intervention,
with scores falling from those of clinical significance to those more
representative of non-feeding-problem children. Regression analysis indicated
that children's problem scores on the BPFAS predicted 15% of the variance in
increased dietary variety following the intervention. The outcome of this
evaluation indicated that improving dietary variety in children with clinically
significant feeding problems is challenging. With the right approach, however,
large improvements can be observed relatively quickly.
PMID- 28520096
TI - A randomized control trial of integrated care for families managing infant colic.
AB - This article presents a randomized clinical trial examining the effectiveness of
a unique model of integrated care for the treatment of infant colic. Families
seeking help for infant colic were randomized to either the family-centered
treatment (TX; n = 31) or standard pediatric care (SC; n = 31). All parents
completed 3 days of Infant Behavior Diaries (Barr et al., 1998) and the Colic
Symptom Checklist (Lester, 1997), Beck Depression Inventory (Beck & Steer, 1984),
and Parenting Stress Index 3rd ed.-SF (Abidin, 1995). TX families were seen three
times by a pediatrician and a mental health clinician within 1, 2, and 6 weeks of
baseline data. TX families received individualized treatment plans addressing
problem areas of sleep, feeding, routine, and family mental health. SC families
were seen only by their own healthcare provider. All families were visited at
home by a research assistant to retrieve data at 2, 6, and 10 weeks after
baseline. Family-based treatment accelerated the rate of reduction of infant
crying faster than did standard pediatric care. Infants in the TX group had more
hours of sleep at 2 weeks posttreatment and spent less time feeding at 2, 6, and
10 weeks posttreatment than did SC infants. Results indicate that individualized
family-based treatment reduces infant colic more rapidly than does standard
pediatric care.
PMID- 28520097
TI - Depressive-symptom onset during toddlerhood in a sample of depressed
preschoolers: Implications for future investigations of major depressive disorder
in toddlers.
AB - This study investigated the occurrence of depressive symptoms prior to age 36
months as retrospectively reported by parents of preschoolers with clinical
depression. The study provides some of the first empirical data on the
manifestations of depressive symptoms during the toddler period, advancing
existing theoretical and case-report literature. A sample of 301 (depressed,
disruptive, and healthy) children between the ages of 3.0 and 6.0 years were
screened and oversampled for depressive symptoms from community sites. Primary
caregivers (parents) were interviewed about their child's symptoms of depression
(as well as other symptoms of mental disorders and developmental parameters), and
age of first onset of depressive symptoms was ascertained. Findings suggest that
clinical-level symptoms of depression may arise as early as age 24 months. The
domain of negative self-concept during the toddler period evidenced by self
deprecation and difficulty making choices emerged as the two strongest variables
predictive of preschool depression. Our results suggest that prospective
empirical studies of depressive symptoms in children younger than 3 years of age
should now be undertaken.
PMID- 28520098
TI - Development of regulation disorders into specific psychopathology.
AB - Underlying deficits in self-regulation and sensory processing are seen in
children with regulation disorders (RD) and might lead to emotional and
behavioral problems as the child develops. However, little is known about the
specific developmental course of RD. This follow-up study was conducted to
investigate the development of a clinical sample of RD children, diagnosed by
means of the Diagnostic Classification of Mental Health and Developmental
Disorders of Infancy and Early Childhood, Revised (DC:0-3R; ZERO TO THREE, 1994),
toward specific psychopathology 4 to 10 years later based on parent- and teacher
reports on the Child Behavior Checklist (T.M. Achenbach & L.A. Rescorla, 2007).
Parental reports showed that 39 to 69% of children with RD had internalizing,
externalizing, and total problems above borderline cutoffs, as compared to norm
group data (16%). In addition, higher rates of affective, anxiety, attention
deficit/hyperactivity, oppositional defiant, and conduct problems were reported.
Analyses between RD subtypes showed significant differences on future attention
problems and rule-breaking behavior, wherein less favorable results were found
for the Hypersensitive subtype Type A (fearful/cautious) in comparison to the
sensory stimulation-seeking/impulsive subtype. The current results indicate
persistence of emotional and behavioral problems into middle childhood and
adolescence in children with preschool RD diagnoses. More attention should be
paid to differentiation of psychopathology in these children since developmental
outcomes may differ between RD subtypes.
PMID- 28520099
TI - Maternal representations and emotional availability among drug-abusing and
nonusing mothers and their infants.
AB - Both negative and idealized maternal prenatal representations may constitute a
risk for mother-infant interaction. This study analyzed the role of maternal
prenatal representations and pre- to postnatal representational change in
predicting mother-infant emotional availability (EA) among 51 drug-abusing
mothers and their infants who participated in either psychodynamic group therapy
(PGT) or received psychosocial support (PSS) and among 50 nonusing comparison
dyads. Maternal representations of her child, the child's father, her own mother,
self-as-mother, and self-as-woman were measured during pregnancy and at 4 and 12
months' postpartum with the Interview of Maternal Representations (M. Ammaniti et
al., 1992; M. Ammaniti, R. Tambelli, & P. Perucchini, 1998). EA was measured with
the Emotional Availability Scales, fourth edition (Z. Biringen, 2008) at 4 and 12
months. The results showed that drug-abusing mothers had more negative prenatal
representations of the self-as-woman and of the child's father. Postnatally, PSS
mothers tended to first idealize their child, but later to experience
disillusionment of idealization. Both negative and idealized prenatal
representations of the self-as-mother predicted mother-infant EA problems, but
only among the PGT mothers. For all mothers, negative representational change was
detrimental for the mother-infant EA whereas for drug-abusing mothers, also
increasing idealization from the prenatal period to the postnatal period was
harmful. Clinicians working with drug-abusing mothers should aim at supporting
the development of a realistically positive view of motherhood.
PMID- 28520100
TI - Early childhood trichotillomania: Initial considerations on phenomenology,
treatment, and future directions.
AB - Historically, trichotillomania (TTM) in young children (0-3 years old) generally
has been considered to be a benign habit that is clinically distinct from the TTM
seen in older children and adults. However, early childhood TTM can be an
impairing pathological disorder that merits formal intervention. The present
article reviews the extant literature on TTM in young children, highlighting the
limited available phenomenological data. We discuss a behavioral approach to
conceptualization and treatment, highlighting core intervention strategies in
three early childhood TTM cases seen in our clinic. We conclude by discussing
areas in need of further empirical attention.
PMID- 28520101
TI - Transition and moving forward.
PMID- 28520102
TI - Etiology of preschool behavior problems: Contributions of temperament attributes
in early childhood.
AB - The present study was conducted to examine the contributions of early appearing
temperament attributes to toddler and preschool-age behavior problems. High
levels of negative emotionality and low levels of effortful control were linked
to both externalizing and internalizing difficulties. All fine-grained dimensions
of negative affect were concurrently associated with internalizing problems
whereas relations between components of negative affect and externalizing were
observed only for frustration, sadness, and low falling reactivity. Higher
surgency was associated with increased risk for externalizing behaviors whereas
low surgency increased the likelihood of internalizing problems. Trait-by-trait
moderation occurred, such that negative emotionality was most closely related to
behavior problems when orienting/regulatory capacity or effortful control was low
or when infant surgency was high. Results of this study have implications for
theory linking temperament and psychopathology, and clinical applications
utilizing temperament assessment to prevent behavior problems.
PMID- 28520103
TI - Circular RNA circMTO1 acts as the sponge of microRNA-9 to suppress hepatocellular
carcinoma progression.
AB - : Noncoding RNAs play important roles in cancer biology, providing potential
targets for cancer intervention. As a new class of endogenous noncoding RNAs,
circular RNAs (circRNAs) have been recently identified in cell development and
function, and certain types of pathological responses, generally acting as a
microRNA (miRNA) sponge to regulate gene expression. Identifying the deregulated
circRNAs and their roles in cancer has attracted much attention. However, the
expression profile and function of circRNAs in human hepatocellular carcinoma
(HCC) remain to be investigated. Here, we analyzed the expression profile of
human circRNAs in HCC tissues and identified circMTO1 (mitochondrial translation
optimization 1 homologue; hsa_circRNA_0007874/hsa_circRNA_104135) as one circRNA
significantly down-regulated in HCC tissues. HCC patients with low circMTO1
expression had shortened survival. By using a biotin-labeled circMTO1 probe to
perform RNA in vivo precipitation in HCC cells, we identified miR-9 as the
circMTO1-associated miRNA. Furthermore, silencing of circMTO1 in HCC could down
regulate p21, the target of oncogenic miR-9, resulting in the promotion of HCC
cell proliferation and invasion. In addition, the tumor-promoting effect of
circMTO1 silencing was blocked by miR9 inhibitor. Intratumoral administration of
cholesterol-conjugated circMTO1 small interfering RNA promoted tumor growth in
HCC-bearing mice in vivo. CONCLUSION: circMTO1 suppresses HCC progression by
acting as the sponge of oncogenic miR-9 to promote p21 expression, suggesting
that circMTO1 is a potential target in HCC treatment. The decrease of circMTO1 in
HCC tissues may serve as a prognosis predictor for poor survival of patients.
(Hepatology 2017;66:1151-1164).
PMID- 28520104
TI - Use of time and adolescent health-related quality of life/well-being: a scoping
review.
AB - : Time use could profoundly affect adolescents' health-related quality of life
(HRQL). Ideally, overall time use patterns would be considered, because
activities within a 24-hour day are inherently correlated (more in one activity
means less in another). This review focused on the associations of (i) overall
time use patterns and (ii) components of time use patterns with HRQL in
adolescents. CONCLUSION: More physical activity, less screen time and
more/adequate sleep, in isolation, are associated with better profile-based HRQL
subscales. Greater understanding of adolescents' overall time use patterns and
HRQL is, therefore, a priority for policy development.
PMID- 28520105
TI - Large-scale computational models of liver metabolism: How far from the clinics?
AB - Understanding the dynamics of human liver metabolism is fundamental for effective
diagnosis and treatment of liver diseases. This knowledge can be obtained with
systems biology/medicine approaches that account for the complexity of hepatic
responses and their systemic consequences in other organs. Computational modeling
can reveal hidden principles of the system by classification of individual
components, analyzing their interactions and simulating the effects that are
difficult to investigate experimentally. Herein, we review the state-of-the-art
computational models that describe liver dynamics from metabolic, gene
regulatory, and signal transduction perspectives. We focus especially on large
scale liver models described either by genome scale metabolic networks or an
object-oriented approach. We also discuss the benefits and limitations of each
modeling approach and their value for clinical applications in diagnosis,
therapy, and prevention of liver diseases as well as precision medicine in
hepatology. (Hepatology 2017;66:1323-1334).
PMID- 28520106
TI - Prophylactic sustained inflation is just one step to preventing bronchopulmonary
dysplasia.
PMID- 28520107
TI - Nine-month-olds' triangular interactive strategies with their parents' couple in
low-coordination families: A descriptive study.
AB - Observing infants in triadic situations has revealed their triangular competence;
namely, their ability to interact with both parents by simultaneously sharing
their attention and affects with them. Infants' triangular interaction is linked
with the coparenting unit's degree of coordination; in high-coordination (HC)
families, parents act as a team in relation to the child, thus drawing clear and
flexible boundaries with them; in low-coordination (LC) families, parents either
avoid direct interaction with each other and include the child in their unit or
join together against the child and exclude him or her, thus drawing inconsistent
boundaries with the child. We explored the interactive strategies of LC 9-month
olds (n = 15) with those of their parents, comparing them with HC parents (n =
23) in two conditions: playing with both parents at the same time and witnessing
their parents' dialogue. LC infants' affects were less positive; they addressed
fewer positive triangular bids to their parents and tended to use a less
triangular interactive mode. Thus, LC infants had fewer opportunities than did HC
infants to acquire skills necessary for coping with triangular interaction.
PMID- 28520109
TI - Children's emotional responsiveness and sociomoral understanding and associations
with mothers' and fathers' socialization practices.
AB - Sixty-two preschoolers (55% boys) were presented hypothetical dilemmas about
moral transgressions. Responses were evaluated in terms of children's emotional
responsiveness, prosocial motives, and readiness to intervene. Mothers and
fathers reported separately on their use of victim-oriented inductions, teaching
reparations, power assertion, and love withdrawal. Four years later, parents
reported on children's behavioral problems, emotion-regulation ability, and
empathy. Mothers reported using more victim-oriented inductions than did fathers,
and girls responded with more personal distress and reported more rule-oriented
motives. Maternal love withdrawal was a positive predictor of empathy and motives
of concern. For fathers, teaching reparations were positively related to
children's sympathy. Interestingly, mothers' power assertion was negatively
related to sympathy at high levels of fathers' power assertion, but not at low
levels. Maternal power assertion during the preschool years was negatively
associated with children's long-term empathy scores. School-age outcomes also
were meaningfully predicted by earlier sociomoral competence.
PMID- 28520110
TI - Behavior problems in young children from low-income families: The development of
a new screening tool.
AB - The purpose of this study was to construct a screening tool, the Early Childhood
Behavior Screen (ECBS), to identify behavior problems and prosocial behaviors in
very young children (1-5 years old) from low-income backgrounds. Field testing of
the initial screening tool was conducted with a representative, diverse sample of
439 parents from a low-income, urban community. The final 20-item scale was
written at a 3.9 grade reading level. Psychometric properties of the ECBS
revealed that the items loaded on two factors, the Challenging Behavior factor
and the Prosocial Behavior factor. Each factor demonstrated high levels of
internal consistency (.87 and .92, respectively). The Challenging Behavior factor
demonstrated adequate levels of concurrent validity (r = .75), sensitivity (r =
.82), and specificity (r = .80) based on its relationship with the Eyberg Child
Behavior Inventory (S.M. Eyberg & D. Pincus, 1999). The Prosocial Behavior factor
is a clinically useful aspect of the ECBS, as it allows researchers and
practitioners to identify the child's positive behaviors as part of a strength
based approach to treatment. The results suggested that the ECBS has potential as
a brief screening tool that is useful in pediatric, psychological, and
educational settings that serve low-income populations to aid in the
identification of young children with challenging behaviors that may require
intervention services.
PMID- 28520111
TI - The good, the bad, and the ambivalent: Quality of alliance in a support program
for young mothers.
AB - The relationship that develops between early childhood service providers and
parents is seen as a critical component in program implementation, although
little is known about how service providers and parents view this relationship.
The current qualitative study examines the helping relationship between doulas
and 12 African American adolescent mothers who participated in a larger study of
prenatal and postnatal support. Mothers and their doulas were interviewed
separately at the beginning and the end of program participation about the
quality of the helping relationship and how they spent their time together.
Content analysis revealed positive, negative, and ambivalent themes in mothers'
and doulas' descriptions of their relationships, although the majority of the
relationships were considered positive. For the most part, doulas and mothers
agreed on the quality of the relationship that they formed with each other.
Mothers were more likely to note the enjoyable aspects of spending time with
their doula while doulas focused more on issues of trust and acceptance. The
young mothers and doulas often considered amount of contact and availability (or
lack thereof) as a sign of the quality of the relationship. Results are discussed
in terms of the professional role of the doula and cultural influences in help
giving behavior.
PMID- 28520112
TI - Proapoptotic signaling induced by deletion of receptor-interacting kinase 1 and
TNF receptor-associated factor 2 results in liver carcinogenesis.
PMID- 28520115
TI - Emotional Expression and Language: A Longitudinal Study of Typically Developing
Earlier and Later Talkers from 15 to 30 Months.
PMID- 28520113
TI - Coparenting interactions observed by the prenatal lausanne trilogue play: An
Italian replication study.
AB - The infant-parent interaction is the focus of interest on early interactive
relational models in the triadic perspective. This approach considers the mother
father-child interaction as the matrix of early competences, which start to
develop well before delivery. This theoretical approach has generated an
observation paradigm, the Lausanne Trilogue Play (LTP; E. Fivaz-Depeursinge & A.
Corboz-Warnery, 1999). The aim of the study was to investigate (a) the
psychometric characteristics of coding of the prenatal LTP procedure and their
comparison with the Lausanne validation studies and (b) the characteristics of
triadic interactions during pregnancy. Ninety-eight nonreferred, primiparous
families were recruited at childbirth courses. In addition to validated
questionnaires, observational data were collected at the seventh month of
pregnancy in the prenatal LTP. The collected data show good reliability of the
LTP coding and a consistent factorial structure in line with the Lausanne
validation studies (C. Carneiro, A. Corboz-Warnery, & E. Fivaz-Depeursinge, 2006;
N. Favez et al., 2006). The Structure of the Play and the Intuitive Parenting
Behaviors Scales seem the most representative dimensions in the prenatal period.
Coparental abilities during pregnancy represent an interactive matrix for the
construction of early family relations and may be considered as protective
factors in the child's development of early triadic interactive abilities.
PMID- 28520116
TI - Emotional Expression and Language: A Psycholinguistic Perspective: Commentary to
Kubicek & Emde, Emotional Expression and Language: A Longitudinal Study of
Typically Developing Earlier and Later Talkers from 15 to 30 Months.
PMID- 28520117
TI - From the Start: Integration of Affect and Language in Parent-Infant Interactions:
Commentary to Kubicek and EMDE, Emotional Expression and Language: A Longitudinal
Study of Typically Developing Earlier and Later Talkers from 15 to 30 Months.
PMID- 28520118
TI - Reflective family play: A model for whole family intervention in the infant and
preschool clinical population.
AB - This article proposes a new treatment model, Reflective Family Play, for clinical
intervention in two-parent families of children aged 0 to 5 years. It is play
based and grounded in the evidence-based treatment approach of Watch Wait and
Wonder (WWW) as well as the assessment tool known as the Lausanne Family Play
paradigm (LFP). WWW is a dyadic treatment for caregivers and their infants or
preschoolers that has been shown to shift attachment in the very young (N.J.
Cohen, E. Muir, & M. Lojkasek, 1999; N.J. Cohen, M. Lojkasek, E. Muir, R. Muir &
C.J. Parker, 2002). The LFP is a more recent adaptation of the Lausanne Trilogue
Play paradigm (LTP; E. Fivaz-Depeursinge & A. Corboz-Warnery, 1999). Together,
the LTP/LFP have now been used for over 2 decades as reliable measures of the
family alliance and interactions in two-parent households. By combining concepts
from WWW and the LTP/LFP, a novel approach is presented for treatment in two
caregiver households. Clinical excerpts are used to illustrate.
PMID- 28520119
TI - Emotional Expression and Language: A Longitudinal Study of Typically Developing
Earlier and Later Talkers from 15 to 30 Months.
AB - Children's emotional expression and language both develop during infancy and
early childhood, yet these two communication systems have been studied primarily
in isolation. This study focuses instead on assessing the relation between them
just as productive language emerges during toddlerhood. Seventy-seven typically
developing, firstborn toddlers and their families were recruited at 13 months of
age. Using an extreme groups design, earlier and later talkers were selected
based on their MacArthur Communicative Development Inventory production scores.
Laboratory visits occurred at 15, 21, and 30 months; home visits occurred at 3
month intervals from 15 to 30 months. Observational and parent report measures
assessed child language, emotional expression, temperament, and overall
developmental functioning. Parents also reported on parenting stress and family
life events. Overall, results support a significant relation between emotional
expression and productive language that varies according to the specific emotion,
a finding that may resolve earlier contradictory results in this area. Earlier
talkers expressed more joy/pleasure than did later talkers, but later talkers
expressed more fear and anger than did earlier talkers. Potential contributions
of various child/family factors were explored. Child temperament is proposed as
influencing this relation through its effects on the child's transactions with
the caregiving environment.
PMID- 28520120
TI - The Relationship between Temperamental Negative Affect, Effortful Control, and
Sensory Regulation: A New Look.
AB - Temperamental negative affectivity (NA) and effortful control (EC) have long been
of interest to psychologists, but sensory regulation (SR) has received less
attention. Using confirmatory factor analysis, the present study reexamined the
Rothbart model of EC and NA using the Children's Behavior Questionnaire (CBQ;
M.K. Rothbart, S.A. Ahadi, K.L. Hershy, & P. Fisher, 2001), along with
alternative models of EC, NA, and SR using the CBQ and Short Sensory Profile. The
results failed to replicate the Rothbart model of EC and NA, which includes SR
within the EC and NA factors. A good fit was found for a three-factor model (EC,
NA, and SR) that was replicated in a holdout sample. A three-factor model also
showed a good fit when EC, NA, and SR items similar to symptoms of behavior
problems were eliminated.
PMID- 28520122
TI - A Study of Emotional Expression and Language: Implications for Studying and
Understanding Development of Emotions: Commentary to Kubicek and Emde, Emotional
Expression and Language: A Longitudinal Study of Typically Developing Earlier and
Later Talkers from 15 to 30 Months.
PMID- 28520123
TI - Getting Ready: Results of a Randomized Trial of a Relationship-Focused
Intervention on the Parent-Infant Relationship in Rural Early Head Start.
PMID- 28520124
TI - Report on the natural interruption of pregnancy related to menarche in the
population of Madrid.
AB - All cases of spontaneous abortion which were registered between June 1982 and
June 1984 in the Ciudad Sanitaria de la Paz have been studied in Madrid (n =
1,259). Together with the women who had miscarriages, a control sample of women
(n = 1,016) of similar socioeconomic status and ages was analyzed. The main aim
of this study is the analysis of the link between the age of menarche and the
incidence of miscarriage, as well as morphological characteristics of women. Our
results demonstrate that the average age of menarche is earlier in the sample of
women who have a miscarriage (P > .001). When women are classified by early,
middle, or late age at menarche, it was observed that, for the sample of women
who had a miscarriage, there is a higher percentage of both early and late age at
menarche. No significant differences were found in the rest of the morphological
variables which were considered. The cycles of women who had miscarriages were
more irregular than those in the control group.
PMID- 28520125
TI - Contributions of nutrition versus hypoxia to growth in rural Andean populations.
AB - Previous research on diet and nutrition among peasant agriculturalists in the
Andes has produced inconsistent results. As a consequence it has been difficult
to determine the extent to which nutritional factors contribute to the slowed,
prolonged growth and resultant small adult body size that is characteristic of
these highland populations. The study examines patterns of diet and growth in the
rural highland community of Nunoa, Peru (elevation 4,000 m), and compares them to
similar data collected on this community during the 1960s. Additional data from
other locations in the Andes are then evaluated to discern critical determinants
of growth variation. Analyses of the Nunoan data indicate that nutritional
factors have played a significant role in shaping statural growth at this
location. Comparisons of other growth surveys indicate that Nunoans remain among
the smallest of all Andean populations. Additionally, urban/rural differences in
growth are quite evident in the highlands, with the magnitude of this difference
being greater than in other regions (i.e., coastal or jungle). It appears that
income level and access to land strongly interact to direct and constrain food
consumption patterns. The resulting differences in nutrition, in turn, appear to
be strong predictors of growth variation. Consequently, studies that consider 1)
dietary intake, 2) level of variability in diet, and 3) relative contributions of
purchased and home-produced food to diet should contribute to furthering our
understanding of growth variation in the Andes.
PMID- 28520126
TI - Mortality among Serere children in Senegal.
AB - Seasonal variation in nutritional status and child survival was studied in a
representative sample of 40 Serere households in a rural area in Senegal. Hazard
models (Gage: Am. J. Phys. Anthropol. 76: 429-441, 1988, Rosenberg: J. Biosoc.
Sci. 21(3): 335-348, 1989) were used to investigate risk factors associated with
child mortality in a Senegalese rural area. Not surprisingly the most important
risk factor was the child's nutritional status, as reflected in the BMI. These
models can incorporate sequentially observed information and in this way it
becomes clear how a falling relative BMI manifested itself in a sharply rising
hazard rate. In addition to the BMI, we investigated other risk factors and their
relation to child survival. Of these, birth rank and mother's age were seen to be
associated with survival and all the more so in the presence of an unfavourably
evolving BMI.
PMID- 28520127
TI - Increased diffusion capacity maintains arterial saturation during exercise in the
Quechua Indians of Chilean Altiplano.
PMID- 28520128
TI - Birth seasonality in a Rural U.S. county, 1911-1979.
AB - This paper examines birth seasonality in a rural U.S. county over the period 1911
1979. Data were taken from the complete series of birth certificates for the
county population during this period. Birth seasonality was expected to reflect
seasonal variation in agricultural workload earlier in the century (pre-1940) but
to disappear as this population became more integrated into the wage labor market
from 1940 to 1979. The pattern of birth seasonality in each decade from the 1910s
to the 1970s by week, month, and season was analyzed with descriptive and
analytic techniques. However, no birth seasonality was found for any decade
during this century. The absence of a seasonal fertility pattern remained when
all births were examined, and when such factors as ethnicity (only births to
white mothers), occupation (only births to women married to farmers), and
stillbirths were controlled singly and in combination. The implications of the
lack of birth seasonality in this population are discussed in terms of the
understanding of the causes of birth seasonality and the place of birth
seasonality in human adaptation.
PMID- 28520129
TI - Developmental responses to high-altitude hypoxia in Bolivian children of European
ancestry: A test of the developmental adaptation hypothesis.
AB - The developmental adaptation hypothesis (DAH) proposes that highlanders adapt to
their hypobaric hypoxic environment during growth and development. This report
utilizes data on children (9.0-19.9 yr) of European ancestry residing in Santa
Cruz and La Paz, Bolivia, to test selected aspects of the DAH. Previous tests of
this hypothesis have been hampered by difficulties in controlling for
socioeconomic and genetic influences. However, due to their high socioeconomic
status and their relatively short history of residence at high altitudes, these
factors can be reasonably well controlled in studies of European children. The
data on European children are consistent with some but not all aspects of the
DAH. First, examination of the available data on VO2 max (ml/kg/min) in European
boys suggests that chronic exposure to hypobaric hypoxia results in an
enhancement of the overall functional capacity of the oxygen transport system
during adolescence, as predicted by the DAH. Second, chronic exposure to
hypobaric hypoxia results in a delay in linear growth and maturation in European
children, as well as in an enhancement of their lung volumes, also as predicted
by the DAH. However, the effects of chronic hypoxia on linear growth, after
controlling for health and nutritional status, are not as large as previously
believed and, contrary to the expectations of the DAH, they need not be acquired
through a distinctive pattern of growth during late childhood and adolescence.
Instead, it appears that these patterns are established in European highlanders
prior to 9 years of age and are then maintained, rather than accentuated, during
later developmental periods.
PMID- 28520130
TI - Birth order effects on dermatoglyphs on fingers, palms, toes, and soles.
AB - Coefficients of correlation of 47 dermatoglyphic traits with birth order vary
widely in a sample of 145 sibships of a Bengali speaking population. In general,
ridge-counts and pattern intensities tend to decrease with birth order. Linear
effects of birth order are, however, significant in samples of two sexes only for
ridge-counts on the ab regions of palms and on toes, and in males only for
triradial number on toes, D-line exit, hallucal ridge-count and triradial number
on soles, and ridge-count on index fingers. Their relative intensities do not
follow the order of appearance or of heritabilites of the traits. The maximal atd
angle, which has a negligible correlation with birth order, shows no consistent
trend of a linear or non-linear change with birth order in the two sexes even
within sibships.
PMID- 28520131
TI - Ventilation and the control of erythropoiesis in high-altitude natives of Chile
and Nepal.
PMID- 28520132
TI - Epilogue.
PMID- 28520133
TI - Introduction.
AB - A basic premise of studies conducted in the 1950s and 1960s was that humans
exhibited a uniform set of biological responses to the high altitude environment.
Since then, investigations have been carried out in the North American Rockies,
South American Andes, and the Himalayas by researchers from a variety of
disciplines-biological anthropology, respiratory physiology, cardiology,
hematology, and nutrition. These studies have contributed important insights for
understanding the mechanisms involved in adaptation to high altitude and have
revealed possible differences in the strategies of adaptation exhibited by the
world's various high altitude populations. However, the findings have sometimes
been slow to percolate across disciplinary boundaries, given the tradition among
the biological sciences to conduct research and present findings in specialized
groupings. This symposium breaks this pattern by bringing together from several
disciplines investigators who are actively involved in the conduct of high
altitude studies. The interaction afforded enables us to realize that
understanding the process of human adaptation to high altitude requires a
holistic approach whereby the expertise of various scientific disciplines needs
to be utilized in a synchronized and integrated manner.
PMID- 28520134
TI - Estimation of total body composition by regional dual photon absorptiometry.
AB - The accuracy of estimating total body composition from dual photon absorptiometry
(DPA) and the soft tissue attenuation ratio (Rst) from regional scans over the
abdomen was investigated in a group (n = 82) of young adult (age = 17-38 years)
females with diverse activity histories. Forearm bone mineral content (BMC) was
estimated from single photon absorptiometry. Lumbar vertebrae and femur BMC, and
trunk (lumbar region) soft tissue composition (Rst) were estimated from DPA.
Percent body fat, the criterion variable, was estimated from body density (BD)
after adjusting for individual variation in BMC, an important source of
variability in body density. The test-retest reliability of Rst, assessed in a
second group of subjects (n = 30), was excellent (r = 0.99; SEM = 0.10%). Rst was
significantly (P <= .05) correlated with body density (r = .78), limb and
especially trunk skinfolds, and predicted total body fat (%) with an SEE of 3.9%.
These results demonstrate that DPA is a useful technique for obtaining estimates
of both bone mineral and soft tissue composition, particularly in populations
suspected to have significant bone loss. Given the association between Rst and
trunk (abdominal) fat, DPA may prove to be a useful technique for investigating
the association between abdominal fat and disease.
PMID- 28520135
TI - Variation in hemoglobin concentration among samples of high-altitude natives in
the Andes and the Himalayas.
AB - This paper presents data on hemoglobin concentration in a rural Andean sample at
3,800-3,900 m and incorporates them into a review intended to evaluate possible
sources of the range of variation in mean hemoglobin concentration among samples
obtained at high altitude. Between 3,400 and 4,000 m, rural Himalayan highlanders
average 1.4 gm/dl lower mean hemoglobin concentration than rural Andean
highlanders. With respect to potential causes of anemia, it is concluded that the
relatively low values of rural Himalyan populations are not explicable by lower
hypoxic stress or different techniques of obtaining and analyzing blood samples
and are probably not explicable by nutritional deficiency and disease. With
respect to potential causes of polycythemia within Andean populations, it is
concluded that the somewhat higher values of some mining and urban samples of
Andean higlanders may not be due to the mining occupation per se but may be due
partly to the inclusion of European and mestizo (with at most 500 years of high
altitude ancestry) along with Amerindian highlanders (with millenia of high
altitude ancestry) as well as to the inclusion of highlanders living well above
their own habitual altitudes of residence. The Andean polycythemia is probably
not due to obesity, high androgen levels, or frequent intermittent hypoxemia
during sleep. The effect of heavy smoking cannot be evaluated. Further work on
hematological adaptation to high altitude must pay special attention to sample
characteristics.
PMID- 28520136
TI - Editorial.
PMID- 28520137
TI - Ethnic variation in the size of infant at birth.
AB - The impact of ethnicity and other maternal factors (BMI, parity, glucose
tolerance, gestational age) on the size of the infant at birth was investigated
in a relatively low socioeconomic status, multi-ethnic population at San
Francisco General Hospital. A sample of 2,069 infants born to mothers of black,
non-Hispanic white, Hispanic, and Chinese descent and whose mothers had received
prenatal care at San Francisco General Hospital were studied. Maternal size,
pregnancy history, and blood glucose were determined prenatally at 26-28 weeks
gestation. Anthropometry was performed on the infant within 72 hours of birth.
Black and Chinese infants were the lightest in weight, while Hispanic infants
were the heaviest. When correction was made for maternal factors black infants
were shown to be significantly (P < .05) lighter in birth weight than non
Hispanic white, Chinese, or Hispanic infants. Black infants were also
significantly shorter in birth length and smaller in chest circumference. Chinese
infants had significantly (P < .05) greater adiposity, as indicated by the sum of
skinfold measurements, than both black and Hispanic infants. These findings are
relevant to current practices in neonatal growth categories which are determined
solely by birth weight and do not account for variations in body composition.
Comparisons with a relatively higher socioeconomic status sample from Kaiser
Permanente Hospital (Oakland) shows a similar prevalence of low birth weight
among blacks. These results support other results that ethnicity is a major
independent influence on the weight of the newborn.
PMID- 28520138
TI - Maternal O2 transport and fetal growth in Colorado, Peru, and Tibet high-altitude
residents.
AB - Human populations have lived at high altitudes for lengths of time which are
likely to be shortest in Colorado, intermediate in Peru, and longest in Tibet. We
hypothesized that the longest-resident high-altitude populations have beccome
better adapted than shorter-resident groups as a result of superior abilities to
transport and/or utilize O2 . Because birth weights are reduced at high altitude
and decreased birth weight is associated with increased infant mortality, our
criterion for assessing adaptation was preservation of birth weights close to
values associated with the lowest mortality risk. Colorado (3,100 m) and Peru
(4,300 m) birth weights averaged 3,186+/-70 g and 2,920+/-90 g respectively. A
sample of 15 births from Tibet (3,658 m) weighed 3,307+/-110 g which was more
than their altitude counterparts and close to sea-level norms. Pregnancy
increased maternal ventilation at all three study sites. In Peru, the resultant
elevation in arterial O2 saturation offset the pregnancy-induced fall in
hemoglobin concentration to preserve arterial O2 content at nonpregnant levels.
Arterial O2 content decreased slightly in Colorado and more markedly in Tibet in
the pregnant compared to the nonpregnant state. The Colorado and Peru women with
the greatest rise in ventilation and ventilatory sensitivity to hypoxia produced
the heaviest birthweight infants, suggesting that maternal arterial oxygenation
was an important determinant of fetal growth. The pregnant women in Tibet did not
have higher levels of arterial O2 content than the pregnant Colorado or Peru
women nor did maternal arterial O2 content relate to birth weight in Tibet.
Infant birth weight in Tibet tended to be correlated with the ratio of uterine
artery to common iliac artery mean flow velocity, suggesting that redistribution
of lower-extremity blood flow to favor the uterine circulation may have acted to
augment uterine O2 delivery in the Tibet women. Thus, the limited data available
suggested that the Tibetans may be better adapted as judged by less fetal growth
retardation and may utilize maternal O2 transport mechanisms not reliant upon
increased arterial O2 content.
PMID- 28520139
TI - Applications of anthropometry to epidemiologic studies of nutrition and cancer.
AB - Epidemiologic research on cancer has recently expanded into new areas of
investigation directly related to aspects of human biology, such as human diet
and nutrition. The overall pattern of scientific evidence has suggested that
dietary patterns in early life, as well as in adulthood, may be related to the
long-term risk of certain cancers. Anthropometry has considerable potential in
cancer research as an indirect means of both childhood and adult nutritional
assessment. Anthropometry has advantages in application to cancer studies when
the sample size is large, as it must be to test most contemporary diet-cancer
hypotheses. The anthropometric dimensions selected for measurement should be
reliable, readily accessible in field or clinical situations with high rates of
subject participation, have established correlations to other body dimensions,
and be comparable to dimensions measured in other studies. Appropriate standards
of practice and quality control procedures in cancer studies may differ somewhat
from those employed in human growth studies. Anthropometry is an important
biomedical research methodology, which may be used to study the relations between
nutrition, body size, and cancer, leading to better identification of individuals
and human populations at increased risk.
PMID- 28520141
TI - Quality of attachment, perinatal risk, and mother-infant interaction in a high
risk premature sample.
AB - Thirty-three families, each with a premature infant born less than 33 gestational
weeks, were observed in a longitudinal exploratory study. Infants were recruited
in a neonatal intensive care unit, and follow-up visits took place at 4 months
and 12 months of corrected age. The severity of the perinatal problems was
evaluated using the Perinatal Risk Inventory (PERI; A.P. Scheiner & M.E. Sexton,
1991). At 4 months, mother-infant play interaction was observed and coded
according to the CARE-index (P.M. Crittenden, 2003); at 12 months, the Strange
Situation Procedure (SSP; M.D.S. Ainsworth, M.C. Blehar, E. Waters, & S. Wall,
1978) was administered. Results indicate a strong correlation between the
severity of perinatal problems and the quality of attachment at 12 months. Based
on the PERI, infants with high medical risks more frequently tended to be
insecurely attached. There also was a significant correlation between insecure
attachment and dyadic play interaction at 4 months (i.e., maternal controlling
behavior and infant compulsive compliance). Moreover, specific dyadic interactive
patterns could be identified as protective or as risk factors regarding the
quality of attachment. Considering that attachment may have long-term influence
on child development, these results underline the need for particular attention
to risk factors regarding attachment among premature infants.
PMID- 28520142
TI - Which preventive interventions effectively enhance depressed mothers'
sensitivity? A meta-analysis.
AB - Improving depressed mothers' sensitivity is assumed to be a key element in
preventing adverse outcomes for children of such mothers. This meta-analysis
examines the short-term effectiveness of preventive interventions in terms of
enhancing depressed mothers' sensitivity toward their child and investigates what
type of intervention is most effective. Thirteen interventions, reported in 10
controlled outcome studies, met the inclusion criteria (N = 918). Meta-analytic
results showed a small to medium, significant mean effect size (g = 0.32) with
large variation in individual effect sizes (-0.56-1.76). Interventions including
baby massage were highly effective in improving maternal sensitivity (g = 0.85).
In contrast, individual therapy for the mother proved ineffective in terms of
improving maternal sensitivity (g = -0.00). Two other significant predictors of
greater effect sizes were the inclusion of a support group and the use of a
higher number of intervention methods; however, the significance of these results
was largely accounted for by one single study. Our meta-analysis confirms that
depressed mothers' sensitivity can be improved by preventive intervention and
suggests that baby massage may be an effective intervention method to evoke short
term changes in maternal sensitivity. It is unclear whether these changes are
maintained over time.
PMID- 28520140
TI - Identification of Breast Cancer Inhibitors Specific for G Protein-Coupled
Estrogen Receptor (GPER)-Expressing Cells.
AB - Together with estrogen receptors ERalpha and ERbeta, the G protein-coupled
estrogen receptor (GPER) mediates important pathophysiological signaling pathways
induced by estrogens and is currently regarded as a promising target for ER
negative (ER-) and triple-negative (TN) breast cancer. Only a few selective GPER
modulators have been reported to date, and their use in cancer cell lines has
often led to contradictory results. Herein we report the application of virtual
screening and cell-based studies for the identification of new chemical scaffolds
with a specific antiproliferative effect against GPER-expressing breast cancer
cell lines. Out of the four different scaffolds identified, 8-chloro-4-(4
chlorophenyl)pyrrolo[1,2-a]quinoxaline 14 c was found to be the most promising
compound able to induce: 1) antiproliferative activity in GPER-expressing cell
lines (MCF7 and SKBR3), similarly to G15; 2) no effect on cells that do not
express GPER (HEK293); 3) a decrease in cyclin D1 expression; and 4) a sustained
induction of cell-cycle negative regulators p53 and p21.
PMID- 28520143
TI - Exploration of the links among fathers' unresolved states of mind with respect to
attachment, atypical paternal behavior, and disorganized infant-father
attachment.
AB - Atypical maternal behavior has consistently been identified as a precursor of
disorganized infant-mother attachment, but to date, no research has examined the
role of atypical paternal behavior in the development of disorganized infant
father attachment. This study aims to enhance our understanding and
conceptualization of infant-father attachment by examining the role of fathers'
unresolved states of mind and the display of atypical paternal behavior in the
development of disorganized infant-father attachment. Thirty-one middle-class
couples participated in this study. Maternal and paternal Adult Attachment
Interviews (C. George, N. Kaplan, & M. Main, 1996) were completed prenatally and
at infant age 6 months, respectively. Infant-mother and infant-father dyads
participated in the Strange Situation paradigm (M. Ainsworth, M. Blehar, E.
Waters, & S. Wall, 1978) when the infants were 12 and 18 months of age,
respectively. The Atypical Maternal Behavior Instrument for Assessment and
Classification (E. Bronfman, E. Parsons, & K. Lyons-Ruth, 1999) was used to
assess maternal and paternal behavior during the Strange Situation. Maternal
states of mind regarding attachment predicted infant-mother attachment
relationships, and paternal states of mind predicted infant-father attachment
relationships. Atypical maternal behavior was associated with infant-mother
disorganized attachment; however, atypical paternal behavior did not predict
infant-father disorganized attachment. Thus, it is possible that other factors,
yet to be uncovered, might contribute to the development of infant-father
disorganized attachment.
PMID- 28520144
TI - Deconstructing antenatal depression: What is it that matters for neonatal
behavioral functioning?
AB - This prospective study examined the variability within clinical characteristics
of antenatal maternal depression and cortisol levels for associations with
newborn infant behavior using the Neonatal Behavioral Assessment Scale (NBAS;
T.B. Brazelton, 1984). Participants were 81 pregnant women at risk for perinatal
depression given their histories of depression prior to pregnancy. We took into
consideration not only whether the woman experienced antenatal depression but
also whether the depression met diagnostic criteria and variability in timing
(onset and occurrence) of antenatal depression and symptom severity. Infants of
mothers who became depressed during pregnancy scored less optimally on a subset
of the NBAS scales, specifically those scales related to infant neuroregulation.
Among the clinical characteristics of depression, the fetus' overall exposure to
mothers' depression (reflected in the mean) was most often and most strongly
associated with NBAS scales. In terms of timing, third-trimester exposure was
significantly related to newborn behavior. The findings are discussed within the
S.H. Goodman and I.H. Gotlib (1999) model for transmission of psychopathology to
offspring of depressed mothers.
PMID- 28520145
TI - Evaluating a home-based dyadic intervention: Changes in postpartum depression,
maternal perceptions, and mother-infant interactions.
AB - Psychotherapeutic treatments that focus on improving the relational processes
between mothers with postpartum depression (PPD) and their infants, as well as
the mother's individual therapeutic needs, have a great potential to positively
impact the mother, her infant, and their relationship (K.J. Nylen, T.E. Moran,
C.L. Franklin, & M. O'Hara, 2006). Utilizing pilot data from an evaluation of a
home-based dyadic therapy for mothers with PPD and their infants, this article
reports on a recent academic-community partnership study. The effectiveness of
the intervention was examined, specifically regarding changes in mother's mood,
parenting experience, and relationship with her infant. In addition, associations
were examined among maternal self-report variables measuring change from pre- to
posttreatment in PPD, psychological distress, and maternal perceptions of
parenting and those variables measuring change in observer ratings of maternal
infant interactions. Results showed improvements in mothers' depression,
distress, and perceptions of parenting as well as many ratings of mothers'
interactions with their infants. However, only improvements in maternal
perceptions of parenting, such as maternal self-esteem and parenting stress, were
associated with better mother--infant interactions. Importance of this research
for the field of infant mental health as well as clinical implications are
discussed.
PMID- 28520147
TI - Toward a method for analyzing series of clinical cases.
AB - This article describes the development of this special issue, and emphasizes the
need for a methodology to gather and summarize clinical experience and meta
analyze clinical cases.
PMID- 28520146
TI - Association of tenofovir disoproxil fumarate with primary allograft survival in
HIV-positive kidney transplant recipients.
AB - BACKGROUND: Tenofovir disoproxil fumarate (TDF) is an antiretroviral agent
frequently used to treat human immunodeficiency virus (HIV). There are concerns
regarding its potential to cause acute kidney injury, chronic kidney disease, and
proximal tubulopathy. Although TDF can effectively suppress HIV after kidney
transplantation, it is unknown whether use of TDF-based antiretroviral therapy
(ART) after kidney transplantation adversely affects allograft survival. METHODS:
We examined 104 HIV+ kidney transplant (KT) recipients at our center between 2001
and 2014. We generated a propensity score for TDF treatment using recipient and
donor characteristics. We then fit Cox proportional hazards models to investigate
the association between TDF treatment and 3-year, death-censored primary
allograft failure, adjusting for the propensity score and delayed graft function
(DGF). RESULTS: Of the 104 HIV+ KT candidates who underwent transplantation
during the study period, 23 (22%) were maintained on TDF-based ART at the time of
transplantation, and 81 (78%) were on non-TDF-based ART. Median age of the cohort
was 48 years; 87% were male; 88% were black; and median CD4 count at
transplantation was 450 cells/mm3 . Median kidney donor risk index was 1.2. At 3
years post transplantation, primary allograft failure occurred in 26% of patients
on TDF-based ART and in 28% of patients on non-TDF-based ART (P=.5). TDF
treatment was not associated with primary allograft failure at 3 years post
transplant after adjusting for DGF and a propensity score for TDF use (hazard
ratio 2.12, 95% confidence interval 0.41-10.9). CONCLUSIONS: In a large single
center experience of HIV+ kidney transplantation, TDF use following kidney
transplantation was not significantly associated with primary allograft failure.
These results may help inform management for HIV+ KT recipients in need of TDF
therapy for adequate viral suppression.
PMID- 28520148
TI - A systems perspective on the integrative child psychiatry approach. Discussion of
paper: "Working here and now with the individual and family system: A case of a
traumatized child".
AB - In this discussion, after a few general comments, I will propose a systems
reading of the intervention so elegantly described by Kaija Puura. I will draw
parallels between the therapeutic and the family groups as framing-developing
systems and formalize the steps taken by the family toward healing under the
influence of the therapist's team.
PMID- 28520149
TI - The music of containment: Addressing the participants in mother-infant
psychoanalytic treatment.
AB - The author discusses the psychoanalyst's approach in mother-infant treatments.
Emphasis is given to the infant as an important, though often neglected,
addressee. A clinical example is used in which a telephone call during a prior
session triggered fretting in a 3-month-old girl and distress in her mother. It
is suggested that in the session, nonverbal levels of the interventions reached
the girl and contained her, and that this containment worked along similar lines
as the communicative musicality between mother and baby. In the discussion, the
psychoanalytic concept of containment (Bion, 1962) is linked with the concept of
communicative musicality (Trevarthen & Aitken, 2001). The mother's need for
containment also is emphasized, and the therapist must be on alert when it is
essential to focus on either participant in the therapy room. This choice is
guided both by explicit deliberations and by the unconscious countertransference.
However, the therapist's wish to grasp the countertransference is countered by
his or her unwillingness of being reminded of feelings of infantile helplessness.
Similarly, when the mother's conscious and unconscious messages diverge, the
baby's ability to receive her caretaking is compromised. In the article's
clinical case, this happened when the mother tried to soothe her daughter while
being preoccupied with anger at the therapist to an extent to which she was not
fully aware.
PMID- 28520150
TI - An infant who was born with a life-threatening skin disease: Various aspects of
triadic psychotherapy.
AB - A longitudinal case study of a 3-year-old toddler, born with a congenital,
severe, life-threatening skin disease, with comorbid diagnoses of failure to
thrive and feeding disorder, is described and discussed. The referral,
diagnostic, and therapeutic processes are described, and the main themes of the
treatment sessions are presented in the associative order that they occurred. The
understanding of the case is very much based on the "me-skin'' concept. We have
tried, through this case, to show the ways that we work with multidisciplinary
team countertransferential reactions to the young child and her parents, the role
that the child psychiatrist may take, and the special difficulty in working with
cases that raise fear of death in parents as well as in therapists. We raise
existential questions about worth of life, infant's will to grow, and infant's
drive to live forever a painful life.
PMID- 28520151
TI - Working here and now with the individual and family system: A case of a
traumatized girl.
AB - From the moment of conception, each and every child lives and develops in
connection with other people. Most children grow up in families formed by
parent(s) and siblings, and relationships with them form an important part of the
environment in which they develop. Interaction with parents and siblings affects
brain development and the intrapsychic structures of the child. In the last few
decades, knowledge of both normal and abnormal development of the human brain and
mind has increased, revealing the complicated interplay of neurophysiology,
emotions, and behavior within an individual as well as in interaction with
others. In an attempt to address the challenge of working with various existing
frameworks, in the Child Psychiatric Department of Tampere University Hospital,
Professor Tuula Tamminen started a clinical philosophy called integrative child
psychiatry. It includes looking at a child's situation from different
perspectives and integrating data gathered into clinical understanding to choose
the optimal treatment. In this article, I describe how I used individual child
therapy, family therapeutic methods, psychoeducation, and some simple behavioral
techniques in the treatment of a sexually abused girl.
PMID- 28520152
TI - Understanding changes and children. Discussion of paper: "Child analysis in a
changing world".
PMID- 28520153
TI - Clinical challenges of adoption: Views from Montreal and Tel Aviv.
AB - Adoption is accompanied by well-known risk factors that contribute to unique
clinical challenges for children, parents, and clinicians. Adoption also serves
to illustrate issues that remain relatively "silent" in the typical transition to
parenthood. In this article, the authors review the normal developmental
challenges that parents face during adoption, the adoption-related risk factors
that may impinge on the child's development and attachment process, and the
impact of adoption on the child's development of identity and filiations. We will
review and illustrate clinical conditions often associated with adoption. In many
countries, adoptive parents are reluctant to consult mental health clinicians
during the first year of the adoption. The cases presented here illustrates the
need to implement routine clinical programs for early detection and intervention
of adoptive parent-infant dyads and triads at risk.
PMID- 28520154
TI - Adding some notes to the "Music of Containment". Discussion of paper: "The Music
of Containment: Addressing the participants in mother-infant psychoanalytic
treatment".
AB - Thinking about the psychoanalytical process in parent-infant psychotherapy is the
purpose of Bjorn Salomonsson's article. He proposes to consider that containment
is the core of the treatment and that musicality is his main vehicle. His thought
is linked with the research on primary intersubjectivity and is so exciting for
all the parent-infant therapists. For myself, I emphasize the use of the
psychoanalytical concept of affects rather than emotions, and I present my
understanding of the transference phenomena with the part of the infantile
sexuality of all the participants.
PMID- 28520155
TI - Final comments.
PMID- 28520156
TI - The quality of the relationship as a factor of change. Discussion of paper:
"Challenges working with infants and their families: Symptoms and meanings-two
approaches of infant-parent psychotherapy".
PMID- 28520157
TI - Child analysis in a changing world. In the face of a paradigm shift from the mind
to the brain: Can we meet the challenge?
AB - Child analysts and child therapists are now practicing in a new environment where
an increased emphasis is made on identifying the symptoms and finding the
shortest possible way to get rid of them, from the knowledge of brain
functioning. From that perspective, the history of the symptom, of the child who
owns it, and of the family in which this child is being raised are not emphasized
as strongly. Searching for a specific meaning of such symptoms seems to be of no
more interest. How can such a heavy trend be met? Major changes also have
occurred within the psychoanalytic milieu. Advances from the observational world,
from Spitz (1945) to Bowlby's (1987) attachment theory, provide essential
knowledge to the field of early child-parent interactions. Longitudinal research
in recent decades has shown close ties between early development and future
outcomes. Such new knowledge is inspiring child analysis with very young children
as well as with severely disturbed, older children. Early intervention with
disadvantaged populations is showing the importance of the nonspecific aspects of
the therapeutic relationship as a factor of change. In light of recent
neurobiologic research on the influence of a specific environment-attachment
experiences-on early development of the brain, it is now possible to speak of the
social brain (Cozolino, 2006).
PMID- 28520159
TI - A psychoanalytic view about "Clinical challenges of adoption, views from montreal
and Tel Aviv".
PMID- 28520158
TI - Focusing the lens: The infant's point of view. Discussion of "Brief interventions
with parents, infants, and young children: A Framework for thinking".
AB - This is a discussion of the article "Brief Interventions With Parents, Infants,
and Young Children: A Framework for Thinking by Louise Emmanuel." Questions of
symptom formation, the difference between a defense and developmental phenomena,
and different therapeutic techniques are explored from the perspective of The
Baby as Subject (an infant-parent psychotherapy approach developed at the Royal
Children's Hospital in Melbourne, Australia). The relationship between feeding
difficulties and the dynamics of the infant-parent attachment relationship are
discussed with reference to whether the infant's apparent self-sufficiency is
interpersonally generated and whether bids for autonomy are a sign of healthy,
age-appropriate developmental drives at play. The use of representational toys in
infant-parent psychotherapy to enable infants and toddlers to represent their
experience or for the therapist to visually express what he or she understands
the infant's experience to be and thus to work directly with the infant's
representations is outlined. In addition to the linguistic content of verbal
interpretations, the infant is receptive to the experience of another thinking
mind and the emotional language, facial expressions, and gestures that also
convey to the baby the experience of being understood or misunderstood.
PMID- 28520160
TI - Challenges working with infants and their families: Symptoms and meanings-two
approaches of infant-parent psychotherapy.
AB - In this article, the authors describe the rationale for the way they work with
troubled infant-parent relationships. They focus on two approaches developed at
the Hincks-Dellcrest Children's Mental Health Centre (Toronto, Canada), a
publically funded agency where they work and teach. One approach is Watch, Wait
and Wonder, and the other is Infant-Parent Psychotherapy. The authors share a
common philosophy that directs the way they think about the way they work. Two
clinical case studies are presented to illustrate the treatment process of each
approach. The presenting symptoms in both cases are similar (sleep difficulties),
but the meaning, ages, and family compositions are different. The interventions
unlocked the difficulties that each relationship was experiencing in a brief
period of time.
PMID- 28520161
TI - Opening remarks.
PMID- 28520162
TI - Brief interventions with parents, infants, and young children: A framework for
thinking.
AB - In this article, I give an overview of the "Brief Intervention Model of work with
Under Fives,'' focusing on ways in which observational skills, awareness of
transference and countertransference phenomena, and addressing the underlying
feelings thereby conveyed, can facilitate understanding and change. Two clinical
vignettes illustrate the application of psychoanalytic thinking to work with the
Under Fives Model and the fluctuating shifts of attention involved in trying to
understand the meaning of what is being expressed. This includes the use of the
clinicians' own emotional experience to work out "what the matter can be"
(Emanuel & Bradley, 2008).
PMID- 28520163
TI - The child WHO was born with no skin shield: Reflections on the meanings of
therapy. Discussion of paper: "An infant WHO was born with a life-threatening
skin disease: Various aspects of triadic psychotherapy".
PMID- 28520164
TI - Transition-Metal Chalcogenide/Graphene Ensembles for Light-Induced Energy
Applications.
AB - Recently, nanomaterials that harvest solar energy and convert it to other forms
of energy are of great interest. In this context, transition metal chalcogenides
(TMCs) have recently been in the spotlight due to their optoelectronic properties
that render them potential candidates mainly in energy conversion applications.
Integration of TMCs onto a strong electron-accepting material, such as graphene,
yielding novel TMC/graphene ensembles is of high significance, since photoinduced
charge-transfer phenomena, leading to intra-ensemble charge separation, may
occur. In this review, we highlight the utility of TMC/graphene ensembles, with a
specific focus on latest trends in applications, while their synthetic routes are
also discussed. In fact, TMC/graphene ensembles are photocatalytically active and
superior as compared to intact TMCs analogues, when examined toward
photocatalytic H2 evolution, dye degradation and redox transformations of organic
compounds. Moreover, TMC/graphene ensembles have shown excellent prospect when
employed in photovoltaics and biosensing applications. Finally, the future
prospects of such materials are outlined.
PMID- 28520166
TI - Operator-based variability of equine thromboelastography.
AB - OBJECTIVE: To determine the extent of intraoperator (between duplicate samples)
and interoperator (between different operators) variability in equine
thromboelastography (TEG). DESIGN: Kaolin-activated TEG was performed in
duplicate by operator-pair A/B or A/C (2 groups of 10 horses) using discrete
setups, within 30-45 minutes of vacuum-assisted blood collection. Recorded TEG
variables included clot initiation time (R), clot formation time (K), rate of
clot formation (alpha), clot strength (MA), and viscoelastic/shear strength (G).
Operators independently determined the clinical coagulation status for each
sample. Intra- and interoperator variabilities were reported as coefficients of
variation (CV), using descriptive statistics and paired samples t-test or
Wilcoxon matched pair signed-rank test (P < 0.05 considered significant).
ANIMALS: Twenty hospitalized adult horses with no clinical evidence of systemic
inflammation. MEASUREMENTS AND MAIN RESULTS: Mean intraoperator CVs ranged from
2.6 to 14% (operator A), 2.8 to 13% (operator B) and 1.2 to 18% (operator C).
Both intra- and interoperator variabilities were lowest for MA (1.2-3.2%) and G
(2.9-7.3%), and highest for K (13-23%). Mean CVs for all TEG parameters were
lower when comparing intra- to interoperator variation. Seventy percent of horses
had at least 1 TEG variable (out of 4 replicates) outside the established
reference intervals. Assessment of coagulation status was conserved between
operators in 9/10 and 8/10 horses for A/B and A/C, respectively, with comparable
agreement between operator A/B (k = 0.73) and A/C (k = 0.74). CONCLUSIONS: TEG
measurements of MA and G are more reproducible than assessment of K, within
samples and between operators. The highest test variability was thus observed
within the early phase of clot formation.
PMID- 28520168
TI - Measures of infant behavioral and physiological state regulation predict 54-month
behavior problems.
AB - This study investigated whether measures of infant temperament, regulatory
disorders, and physiological reactivity and concurrent measures of family
environment were predictors of child behavior problems at 54 months of age. The
sample consisted of 23 children-mother dyads. The sample recruitment strategy
emphasized testing both typical and fussy/difficult infants at 9 months of age.
Children were categorized into low and high behavioral problem groups at 54
months of age. The children in the high behavioral problem group were more likely
at 9 months to have been temperamentally difficult, to have been classified as
regulatory disordered, and to have displayed respiratory sinus arrhythmia (RSA)
regulation difficulties. These children also were more likely to come from
families described as less cohesive and providing less focus on
active/recreational activities when the children were 54 months old. A logistic
regression analysis, including only the 9-month infant measures (i.e.,
difficultness, regulatory disorders classification, and RSA regulation), resulted
in a significant model with 100.0% accurate classification into high or low
behavioral problem groups. Data suggest that infant measures of behavioral and
physiological state regulation may be early indicators of child behavior
problems, especially internalizing problems.
PMID- 28520167
TI - KMT2B rare missense variants in generalized dystonia.
AB - BACKGROUND: Recently a novel syndrome of childhood-onset generalized dystonia
originating from mutations in lysine-specific methyltransferase 2B (KMT2B) has
been reported. METHODS: We sequenced the exomes of 4 generalized dystonia
affected probands recruited from a Prague movement disorders center (Czech
Republic). Bioinformatics analyses were conducted to select candidate causal
variants in described dystonia-mutated genes. After cosegregation testing,
checklists from the American College of Medical Genetics and Genomics were
adopted to judge variant pathogenicity. RESULTS: Three novel, predicted protein
damaging missense variants in KMT2B were identified (p.Glu1234Lys, p.Ala1541Val,
p.Arg1779Gln). Meeting pathogenicity criteria, p.Glu1234Lys was absent from
population-based controls, situated in a key protein domain, and had occurred de
novo. The associated phenotype comprised adolescence-onset generalized isolated
dystonia with prominent speech impairment. Although linked to a similar clinical
expression, p.Ala1541Val and p.Arg1779Gln remained of uncertain significance.
CONCLUSIONS: Rare missense variation in KMT2B represents an additional cause of
generalized dystonia. Application of sequence interpretation standards is
required before assigning pathogenicity to a KMT2B missense variant. (c) 2017
International Parkinson and Movement Disorder Society.
PMID- 28520165
TI - Targeting CCl4 -induced liver fibrosis by RNA interference-mediated inhibition of
cyclin E1 in mice.
AB - : Initiation and progression of liver fibrosis requires proliferation and
activation of resting hepatic stellate cells (HSCs). Cyclin E1 (CcnE1) is the
regulatory subunit of the cyclin-dependent kinase 2 (Cdk2) and controls cell
cycle re-entry. We have recently shown that genetic inactivation of CcnE1
prevents activation, proliferation, and survival of HSCs and protects from liver
fibrogenesis. The aim of the present study was to translate these findings into
preclinical applications using an RNA interference (RNAi)-based approach. CcnE1
siRNA (small interfering RNA) efficiently inhibited CcnE1 gene expression in
murine and human HSC cell lines and in primary HSCs, resulting in diminished
proliferation and increased cell death. In C57BL/6 wild-type (WT) mice, delivery
of stabilized siRNA using a liposome-based carrier targeted approximately 95% of
HSCs, 70% of hepatocytes, and 40% of CD45+ cells after single injection. Acute
CCl4 -mediated liver injury in WT mice induced endogenous CcnE1 expression and
proliferation of surviving hepatocytes and nonparenchymal cells, including CD45+
leukocytes. Pretreatment with CcnE1-siRNA reverted CcnE1 induction to baseline
levels of healthy mice, which was associated with reduced liver injury,
diminished proliferation of hepatocytes and leukocytes, and attenuated overall
inflammatory response. For induction of liver fibrosis, WT mice were challenged
with CCl4 for 4-6 weeks. Co-treatment with CcnE1-siRNA once a week was sufficient
to continuously block CcnE1 expression and cell-cycle activity of hepatocytes and
nonparenchymal cells, resulting in significantly ameliorated liver fibrosis and
inflammation. Importantly, CcnE1-siRNA also prevented progression of liver
fibrosis if applied after onset of chronic liver injury. CONCLUSION: Therapeutic
targeting of CcnE1 in vivo using RNAi is feasible and has high antifibrotic
activity. (Hepatology 2017;66:1242-1257).
PMID- 28520169
TI - Risks and outcomes associated with disorganized/controlling patterns of
attachment at age three years in the National Institute of Child Health & Human
Development Study of Early Child Care and Youth Development.
AB - Disorganized/controlling attachment in preschool has been found to be associated
with maternal and child maladjustment, making it of keen interest in the study of
psychopathology. Additional work is needed, however, to better understand
disorganized/controlling attachment occurring as early as age 3 years. The
primary aims of this study were to evaluate risk factors and outcomes associated
with disorganized/controlling behavior at age 3 years and to evaluate the risk
factors and outcomes differentiating the four subtypes of
disorganized/controlling attachment. Analyses were conducted with the first two
phases of the National Institute of Child Health & Human Development Study of
Early Child Care and Youth Development, a prospective study of 1,364 children
from birth. At 36 months of age, across the attachment-relevant domains of
maternal well-being, mother-child interactions, and child social adaptation, the
disorganized/controlling group evidenced the most maladaptive patterns in
comparison to both secure and insecure-organized groups. At 54 months of age, the
disorganized/controlling group displayed the highest levels of internalizing and
externalizing behavior problems, as rated by mothers and teachers, and the lowest
quality relationships with teachers. Significant differences found among the
disorganized/controlling subtypes indicated that the behaviorally disorganized
and controlling-punitive subtypes had more maladaptive patterns across variables
than did the controlling-caregiving and controlling-mixed subtypes.
PMID- 28520170
TI - A social-contextual understanding of concordance and discordance between maternal
prenatal representations of the infant and infant-mother attachment.
AB - This prospective study examined the relationship between maternal prenatal
representations of the infant and later infant-mother attachment, including
contextual factors related to concordance and discordance among dyads over time.
Participants were 173 pregnant women between the ages of 18 and 40 who were
interviewed during their last trimester of pregnancy and 2 and 13 months after
birth. Maternal representations were assessed by the Working Model of the Child
Interview during pregnancy (WMCI; C.H. Zeanah, D. Benoit, L. Hirshberg, M.L.
Barton, & C. Regan, 1994), and infant-mother attachment was assessed through the
Strange Situation procedure (M.D.S. Ainsworth, M. Blehar, E. Waters, & S. Wall,
1978) when infants were 13 months old. There was substantial discordance between
maternal and infant classifications, although a significant concordance rate was
found when classifications were collapsed into balanced/secure and
nonbalanced/insecure groups based on prenatal representations and postnatal
infant attachment groups (60%; chi2 = 6.90, p < .01; kappa .20). As expected,
discordance between maternal representations and infant-mother attachment was
meaningfully related to contextual risk factors, maternal depression, and infant
behaviors.
PMID- 28520171
TI - Music therapy with hospitalized infants-the art and science of communicative
musicality.
AB - Infants seek contingent, companionable interactions with others. Infants in a
Neonatal Intensive Care Unit (NICU), while receiving care that optimizes their
chances of survival, often do not have the kind of interactions that are optimal
for their social development. Live music therapy (MT) with infants is an
intervention that aims for contingent, social interaction between therapist and
infant. This study, with a limited numbers of infants, examined the effectiveness
of an MT intervention in the NICU at The Royal Children's Hospital Melbourne. Two
groups of late pre-term and full-term infants were recruited to the study; one
was given MT and the other was not. A healthy group of infants not given MT
served as an additional control. The effect of MT was indexed using two measures
reflecting infant social engagement: the Neurobehavioral Assessment of the
Preterm Infant (NAPI) and the Alarm Distress Baby Scale (ADBB). Results suggest
that the MT intervention used at The Royal Children's Hospital Melbourne supports
infants' neurobehavioral development. In particular, hospitalized infants who
received MT were better able to maintain self-regulation during social
interaction with an adult, were less irritable and cried less, and were more
positive in their response to adult handling, when compared with infants who did
not receive the intervention. These are important prerequisites for social
interaction and development. Further and larger scale research using MT with this
population is indicated.
PMID- 28520172
TI - Infancy research, infant mental health, and adult psychotherapy: Mutual
influences.
AB - This article considers the influence of infant research on psychodynamic theory
and practice. Infant research highlights the dramatic effects of the early
caregiving relationship on development throughout the life span. It also provides
important perspectives on psychotherapeutic processes. This article highlights
such elements as empathy, mutual recognition and attachment, along with
elaborating the intersubjective and transactional systems perspectives. In
addition, it stresses the powerful role of nonverbal, implicit communication and
meaning-making, which play a greater role in human relational experience-and
therefore in the therapeutic process-than previously understood. In addition to
clarifying these general orientations, the article describes specific therapeutic
strategies based on the expanded developmental knowledge.
PMID- 28520173
TI - Mothers' voices: Coping with their children's initial disability diagnosis.
AB - For parents of infants and toddlers receiving a diagnosis of disability, a
variety of responses may result. Yet, little is known about the specific ways
families cope with the initial diagnosis. This qualitative study investigated 6
mothers' memories of their children's diagnoses. Mothers described their use of
both palliative strategies (denying, questioning, and wishful thinking) and
problem-solving strategies (searching for information, seeking social support,
reframing, and seeking spiritual support) to cope with their children's initial
diagnoses. The results of this study may improve professionals' understanding of
parents' need for information and support at the time of initial diagnosis.
PMID- 28520174
TI - Maternal perceptions of the infant: Relationship to maternal self-efficacy during
the first six weeks' postpartum.
AB - Mothers' perceptions of their infants and their own levels of self-efficacy
contribute to developing maternal-infant attunement. The purpose of this
investigation was to examine the associations between maternal perceptions of
their own infants relative to other infants and maternal self-efficacy in a group
of ethnically diverse, low-income, first-time mothers during the first six weeks
postpartum. By employing a structural equation model approach, we explored
relationships between the predictor (maternal neonatal perceptions) and dependent
variable (maternal self-efficacy). Changes in maternal perceptions of their own
infants significantly contributed to self-reported levels of self-efficacy while
controlling for concurrent self-esteem. Maternal perceptions of her infant as
less difficult than the average infant at six weeks postpartum predicted
increased levels of maternal self-reported self-efficacy. The present study
supports further exploration of the first six weeks postpartum as a sensitive
period for targeting intervention and support, particularly for mothers and
infants at highest risk.
PMID- 28520175
TI - Assessing the prevalence of mental health disorders and mental health needs among
preschool children in care in England.
AB - Although school-aged children living in foster care have been identified as a
high-risk group for mental health and developmental disorders, there is a paucity
of data relating to preschool children in care (CIC). This study aimed to
identify the prevalence of mental health and developmental disorders along with
corresponding need for interventions in preschool CIC. All CIC aged 0 to 5 years
in an inner city local authority underwent comprehensive, multifaceted
assessments consisting of the Ages and Stages Questionnaire (J. Squires, D.
Bricker, & E. Twombly, 2003), interviews with caregivers based on the Preschool
Age Psychiatric Assessment (H.L. Egger & A. Angold, 2006), Mullen Scales of Early
Learning (E.M. Mullen, 1995), and systematic clinical observation. Of 58 eligible
preschoolers, 43 completed the assessment. At least one mental health disorder
was found in 26 (60.5%) participants, and at least one developmental disorder was
found in 11 (25.6%). When mental health and/or developmental disorders were
considered together, 30 (69.8%) preschoolers fulfilled criteria for at least one
diagnosis, and 18 (41.9%) had two or more comorbid conditions. Whereas 36 (83.7%)
of the preschoolers needed an intervention, only 3 of these had received adequate
input. In conclusion, preschool CIC constitute a high-risk group for mental
health and developmental disorders. Without age-appropriate assessments, their
needs go undetected, and opportunities for early intervention are being missed.
PMID- 28520176
TI - What we talked about at the pediatrician's office: Exploring differences between
healthy steps and traditional pediatric primary care visits.
AB - Healthy Steps for Young Children (HS) is a program designed to enhance pediatric
primary care experiences for children birth to 3 years and their families by
pairing a developmental specialist with a pediatric provider during well-child
visits. This study examined the impact of HS on content discussed during well
child visits by providers, HS Specialists, and families. The impact of HS on
pediatric outcomes, including timeliness of well-child visits and immunizations,
also was examined. Using retrospective medical review, records of 40 children
enrolled in HS were compared with records of 36 demographically matched controls.
A developmental topics checklist was used to analyze content of well-child
visits. Attendance at well-child visits, receipt of immunizations, and healthcare
utilization also was evaluated. Important developmental topics were discussed
more often during well-child visits of children enrolled in HS than for children
who were not enrolled. Children enrolled in HS received timelier well-child
visits and immunizations. No differences between groups were found in the number
of sick or emergency room visits. Integrating HS Specialists into pediatric
primary care well-child visits allows for discussion of important developmental
topics while also impacting pediatric health outcomes.
PMID- 28520177
TI - Predicting maternal sensitivity: The roles of postnatal depressive symptoms and
parasympathetic dysregulation.
AB - Previous research has established that maternal depression is a risk factor for a
variety of negative developmental outcomes among infants and children. Although
low levels of maternal sensitivity have been hypothesized to explain this risk,
the biological mechanisms underlying the association between maternal depressive
symptoms and low levels of maternal sensitivity have been largely underexplored.
This study examined the roles of postnatal depressive symptoms and
parasympathetic nervous system functioning as predictors of low levels of
maternal sensitivity, during a stressful mother-infant interaction-the reunion
phase of the Still-Face Paradigm. Depressive symptoms and traitlike
predispositions toward parasympathetic dysregulation, as indexed by low resting
levels of respiratory sinus arrhythmia, were associated independently with less
sensitive parenting. Discussion considers that during stressful mother-infant
interactions, both mothers with depressive symptoms and mothers predisposed to
parasympathetic dysregulation may have fewer emotional, physiological, and
psychological resources with which to respond sensitively to their infants' cues.
PMID- 28520178
TI - Postnatal mental health and parenting: The importance of parental anger.
AB - Parents' postnatal mental health and subjective perceptions of their baby are
likely to influence the quality of their relationship with their baby. To date,
this has largely been examined in mothers; therefore, this study aimed to also
explore this in both parents. Semistructured clinical interviews [The Birmingham
Interview for Maternal Mental Health (BIMMH); Brockingon, Chandra et al., 2006]
were carried out with 85 first-time parents. The BMMHI identifies disorders of
anxiety, depression, PTSD, and parental anger. Sections of the BMMHI also elicit
qualitative accounts of parenthood. These were transcribed and analyzed using
thematic analysis. Differences in the frequency of themes were examined for
parents with or without mental health disorders or parental anger. Themes are
reported for (a) baby characteristics, needs, and development; (b) parents'
emotions, responses, coping strategies, and general parenthood; and (c) parent
and baby relationship. Results indicated that both the presence of parental
mental health problems and, more notably, parental anger were associated with
more negative accounts of the self, the baby, and parenthood. This study provides
insight into first-time parents' perceptions of early parenthood. Results
especially highlight the need to consider parental experiences of anger in more
detail for assessment and interventions in the early postpartum period.
PMID- 28520179
TI - The role of transitions to new age groups in the development of institutionalized
children.
AB - Children in two institutions in St. Petersburg (Russian Federation) experienced
ward transitions, one in which caregivers were trained to provide sensitive,
responsive caregiving and one that conducted business as usual. A third
institution eliminated transitions, received the same training, and implemented a
variety of structural and employment changes designed to promote improved
caregiver-child interactions and relationships. While the no-transition
comprehensive intervention group of children steadily improved in Battelle
Developmental Inventory (LINC Associates, 1988) scores across all age intervals,
the children in the institution who encouraged some positive caregiver-child
interactions improved before and after, but not during, an age period that
involved a transition. In contrast, the no-treatment group displayed no
developmental changes across any age period with or without a transition. These
results suggest that the common institutional practice of ward transitions to new
peers and caregivers is potentially disruptive to infants' and toddlers' general
development, but primarily in a context in which some degree of caregiver-child
sensitive and responsive interactions are encouraged.
PMID- 28520180
TI - SIRT3 as a regulator of hepatic autophagy.
PMID- 28520181
TI - Encapsulation and Polymerization of White Phosphorus Inside Single-Wall Carbon
Nanotubes.
AB - Elemental phosphorus displays an impressive number of allotropes with highly
diverse chemical and physical properties. White phosphorus has now been filled
into single-wall carbon nanotubes (SWCNTs) from the liquid and thereby stabilized
against the highly exothermic reaction with atmospheric oxygen. The encapsulated
tetraphosphorus molecules were visualized with transmission electron microscopy,
but found to convert readily into chain structures inside the SWCNT
"nanoreactors". The energies of the possible chain structures were determined
computationally, highlighting a delicate balance between the extent of
polymerization and the SWCNT diameter. Experimentally, a single-stranded zig-zag
chain of phosphorus atoms was observed, which is the lowest energy structure at
small confinement diameters. These one-dimensional chains provide a glimpse into
the very first steps of the transformation from white to red phosphorus.
PMID- 28520182
TI - Intraductal papillary neoplasm of the bile duct: A rare liver tumor complicated
by malignancy.
PMID- 28520184
TI - Infant feeding and infant health in American Samoa.
AB - This study examines the association between infant feeding patterns and health
for 6,267 Samoan children born between 1976 and 1982, and represented in the Well
Baby Clinic records at the LBJ Tropical Medical Center, American Samoa. The
visits to the clinic were aggregated by trimester of age during the first year of
life. For each trimester, the principal source of milk was determined, and the
children were categorized as breast-fed if they were taking only breast milk,
bottle-fed if they were getting no breast milk, or mixed-fed if they were getting
both breast milk and milk from other sources. Symptoms and complaints noted in
the records were assigned to ICD categories. Associations between source of milk
and disease category were analyzed. The Samoan infants were found to be quite
healthy for a tropical developing population, as evidenced by both growth in
weight and length, as well as by frequency of illnesses. The most common specific
disease category, aside from miscellaneous symptoms, was ICD 8, respiratory
problems. Gastrointestinal diseases were rare for a developing area. There was an
association between source of milk and illness (yes/no) for both the second and
third trimesters. In both cases breast-fed infants were healthier than the mixed
fed infants, and during the second trimester the contrast was significant with
bottle-fed infants also. When examined by ICD category, breast-fed infants tended
to be less likely to have problems in any of the categories, but the only
significant differences were between mixed-fed (lower prevalence) and bottle-fed
infants during the first trimester for ICD 3, primarily nutritional problems; and
for breast-fed (lower prevalence) and mixed-fed infants for ICD 9, digestive
problems. These findings highlight the need for additional household work to
delineate associations with the growth and health of Samoan infants.
PMID- 28520183
TI - Infected malnourished children displayed changes in early activation and
lymphocyte subpopulations.
AB - AIM: Malnutrition and infections cause immunological changes in lymphocyte
subpopulations and their functionality. We evaluated the activation capacity of
lymphocytes and memory cells in 10 well nourished, seven well-nourished infected
and eight malnourished infected children before and after treatment. METHODS: All
the children were patients in Mexico City and were less than three years of age.
The expression of various cluster of differentiation (CD) cells was assessed by
flow cytometry: CD45RA (naive) and CD45RO (memory) antigens on CD4 lymphocytes
and CD69 in all lymphocytes. RESULTS: Well-nourished infected children showed a
higher percentage of activated T lymphocyte (T cells), CD8+ and CD4+ memory cells
during the infectious phase, suggesting that the activation mechanisms were
triggered by infection. T cells from malnourished infected children showed a
lower percentage of activated and memory cells. The T cell population size
returned to baseline during the resolution phase of the infection in well
nourished infected children, but their T, B lymphocyte and natural killer (NK)
cell counts remained high. In malnourished infected children, activated NK cells
counts were low before and after therapy. CONCLUSION: After therapy, malnourished
infected children showed poor NK cell responses during the infection's resolution
phase, suggesting a persistent malnutrition-mediated immunological deficiency.
PMID- 28520185
TI - Correlates of enamel hypoplasia with human dental reduction.
AB - Human dental reduction has been manifested in evolutionary and secular trends,
but it is not known to what degree each of these complementary processes
contributes to changes in tooth size. Enamel hypoplasia is a marker of
developmental stress that is often found to be of greater frequency and severity
in populations undergoing dental size reduction. In order to test the
developmental association of enamel hypoplasia with tooth size, measurements of
bucco-lingual and mesio-distal diameters were taken on teeth of 54 black male
skulls from southern Africa. Those dentitions that exhibited incisal enamel
hypoplasia were significantly reduced in size as compared to those showing no
signs of developmental stress. A distinct pattern of reduction emerged: the bucco
lingual diameters of the I1 , I2 , P3 , P4 , M1 , and M2 were significantly
reduced, whereas the mesio-distal diameters of only the I2 and M2 decreased in
size. The I2 and M2 showed the greatest degree of reduction despite the lack of
macroscopic enamel hypoplasia on the M2 . Application of the data to the variety
of dental reduction patterns evinced in modern and ancient populations indicates
that factors including tooth shape, developmental timing of stress, and genetic
determinants of tooth size must be considered in order to partition evolutionary
and secular trends in the dentition.
PMID- 28520186
TI - Preterm baby delivery: Some genetic epidemiological aspects.
AB - The present paper considers genetic risk factors associated with preterm births.
We investigated two main hypotheses, namely: 1) Whether there is a detectable
genetic or at least a family resemblance component that may predispose a mother
to give birth prematurely and 2) whether the risk to preterm delivery can be
predicted in the early stages of pregnancy by means of associated morphometric
traits and biochemical genetic markers. Our data and published literature
certainly point to the existence of a significant family component, although the
findings are still scanty for precise determination of genetic and cultural
heritability components. In particular, the available data on family correlations
in gestational age do not allow one to distinguish between the contribution of
the fetus's genotype from the maternal environment and maternal genotype. Parent
children and marital correlations in gestational age, critical for nuclear family
analysis, are rather difficult, if not impossible, to obtain. Therefore, we
discuss in the present paper several realistic path analysis models for
estimating the relative contribution of genetically inherited and environmental
components. Some biochemical markers and also morphological asymmetry correlate
with a predisposition to preterm delivery. Again, however, more empirical data
are needed to properly assess these relationships.
PMID- 28520187
TI - Reliability of Tanner stage assessments in a multi-center study.
AB - Tanner stage indices have been frequently used in research studies to
characterize the level of sexual maturation among adolescents. The Cooperative
Study of Sickle Cell Disease (CSSCD) is a large multi-center study in which the
assessment of Tanner stage indices has been performed to describe delays in
sexual maturation and correlates of delays. Rigorous training, however, in rating
Tanner stages was not provided for the clinicians in the study. Data from the
CSSCD were analyzed to characterize the reliability of the assessment of sexual
maturation in this study, and demonstrate the potential for increasing the
reliability by more careful training. In lieu of a gold standard, a maximum
likelihood algorithm was employed to examine the longitudinal consistency of
Tanner stage assessments. Based on the assumption that the underlying process of
sexual maturation is progressive, models were developed that allowed one to
estimate jointly the incidence distribution for the attainment of Tanner stages
and the error rates of assessment. Estimated false-positive rates for assessing
the attainment of Tanner stages from the CSSCD ranged from 2% to 19%. Estimated
false-negative rates ranged from 1% to 18%. The occurrence of these errors was
found not to vary markedly with the subject's age. Error rates of this magnitude
can introduce considerable bias to the estimation of the distribution of Tanner
stages and result in serious losses in relative efficiency. While the validity of
Tanner stage indices can be demonstrated from study data, the loss in statistical
efficiency and power associated with the study error rates was severe. This
underscores the utility of careful training in pubertal rating for research
studies.
PMID- 28520188
TI - Evaluation of physical growth of children in a rainforest community of
northwestern Ecuador.
AB - The physical growth of children under 5 years of age was studied in relation to
patterns of nutrition, morbidity, and health care utilization in three remote
villages of tropical Ecuador. Age-specific comparisons of height and weight to
growth curves from reference populations (US National Child Health Survey)
indicated moderate to severe stunting in the population of male and female
children. Examination of height-weight relationships as a measure of recent
nutritional status provided little evidence that male children were underweight
for their height. However, the observation that female children fell between the
3rd and 50th centile channels of the reference population in their height-weight
relationship suggested moderate wasting in addition to substantial stunting.
Endemic parasitism and a high rate of diarrheal illnesses were detected in the
study population and were likely contributing agents to the stunting observed in
male and female children. No dichotomy in the incidence of diarrhea was detected
between male and female children, and if the episode was mild it was typical not
to treat the illness, regardless of sex. In more severe cases, female children
were more frequently taken to traditional healers. However, when familial self
treatment or local clinics were used, male children were more likely to be the
beneficiary. Thus it seems possible that this advantage, along with the cultural
practice of investing more of the family's resources in male children, may be
responsible for the wasting detected in young females. Tropical conditions,
chronic undernutrition, compromised cellular immunity, and inadequate health care
services were likely causes of the high morbidity and mortality of children under
age 5. Community-based programs of health promotion and disease prevention appear
to offer the best potential as intervention strategies in these villages.
PMID- 28520189
TI - Determining growth faltering with a tracking score.
AB - A tracking score for determining growth faltering in children was developed and
tested. A graphical method was developed for classifying by visual inspection
whether or not a given child had faltered in growth. This method was used to
classify all children in a sample of Guatemalan children as to faltering in both
weight and length between 9 and 24 months of age; 80 of 345 children had faltered
in weight, and 44 of 336 children had faltered in length. The accuracies for
determining this faltering of seven versions of the tracking score and that of
three other commonly used scores were assessed and compared using ROC curves, the
areas under the curves, and two other ways. The other scores tested were the
increment score, the residual score, and a growth-curve parameter score. The
accuracies of the scores were overall lower for weight than for length. For both
weight and length, the growth-curve parameter score had the lowest accuracy, and
the tracking score that used an intermediate number of measurements (four in the
interval of interest and three in the previous interval) had the highest
accuracy. The tracking score has a number of features that make it attractive as
an indicator of faltering. It is easy to calculate and interpret, preserves
magnitude and direction, incorporates several growth measurements into a single
indicator of faltering, gives equal weight to the information in all the
measurements used, allows for missing measurements, and can be generalized to
include other aspects of growth.
PMID- 28520190
TI - Long bone growth velocity in the Libben population.
AB - Growth-attained curves have shown only limited effectiveness in studies of long
bone growth in archaeological populations. As an alternative, the length of long
bone diaphyses in children aged 0 to 12 years from the Libben skeletal collection
were first normalized by average adult long bone length, and derivatives of
fitted curves were then used to determine age-specific growth velocity. The
sample was compared to healthy Euroamerican children from Denver, Colorado
(Maresh: American Journal of Diseases of Children 89:725-742, 1955). Results
indicate almost identical patterns of growth in the two populations with one
exception: the Libben sample shows significantly diminished velocity during the
first three years of life. This period of depressed growth coincides with high
levels of infectious disease.
PMID- 28520191
TI - Effect of tooth size on the ageing and chronological distribution of enamel
hypoplastic defects.
AB - The location of enamel hypoplastic defects on the tooth crown has been used to
determine the age of an individual at the time the defect-producing stress
occurred. The assumptions made in following this methodology are examined, and
one in particular, that tooth size variation has a minimal impact on ageing and
subsequent chronological distributions, is tested. Teeth with no occlusal or
minimal wear and with enamel hypoplasias were measured for crown height and the
location of the defect on the crown. Two samples are used, one comprising a
series of archaeological specimens and the other from modern clinical
extractions. The chronological distributions of the defects are determined by
three different methods: one is based on a tooth mineralization chart; the second
method uses the same chart but incorporates individual crown heights; and the
third method adjusts the chart for the sample's mean crown heights. Significant
differences between the age estimates are observed in both the modern and
archaeological samples. Tooth size does affect the ageing of hypoplastic defects
and the chronological distributions. By adjusting the mineralization chart for
the sample's mean crown heights, the significant differences in age estimates can
be corrected.
PMID- 28520192
TI - A GAUSS program for computing an index of tracking from longitudinal
observations.
AB - Tracking can be defined as the tendency of individuals or collections of
individuals to stay within a particular course of growth over time relative to
other individuals. Thus, tracking describes stability in growth patterns. This
paper outlines a statistical procedure for examining tracking in a single sample
of measurements made on humans or other animals. This nonparametric procedure,
based on Cohen's (1960) kappa statistic, is suitable for equally or unequally
spaced serial data that is complete and is appropriate for questions concerning
growth as well as other time-dependent phenomena. It is a conceptually simple
longitudinal method that affords insight regarding the predictability of growth
within a population. For example, by tracking, one can ask if young children who
are in the lowest height for age category are likely to end up in that category
at an older age. A user-friendly GAUSS program is provided that generates overall
as well as individual and track-specific statistics. High-resolution graphic
representations of the data are also generated by the program. Examples are
presented, including a tracking analysis of Guatemalan Indian children using
quartiles.
PMID- 28520193
TI - Two evolutionary models for the interactions of dietary organic cyanogens,
hemoglobins, and falciparum malaria.
AB - Significant regional and ethnic variations in hemoglobin S frequencies among 485
adult nonpregnant Liberian women uniformly exposed to holoendemic falciparum
malaria suggest that an additional major factor may influence the distribution of
this hemoglobinopathy and the severity of the infectious disease with which it is
causally associated. The differential consumption of organic cyanogen-rich
cassava (Manihot esculenta) foodstuffs and subsequent dosage-dependent in vivo
exposure to sublethal CN- , SCN- , and CNO- may directly interact with hemoglobin
S by inhibiting sickling diathesis, and, at higher intakes, this dietary factor
may adversely affect Plasmodium survival and antigenicity. In this study, low
dietary organic cyanogen intakes (0.3 mg CN- /kg body wt/day) in NW and W
geographical areas are associated with higher regional hemoglobin S gene
frequencies (11%; phenotypic incidence 20%), lower mean (+/- SD) positive
Plasmodium antibody titers (861.6 +/- 102.4), and a higher mean (+/- SEM)
prevalence of clinical falciparum malaria [3.04 times (+/- 0.09) within the
previous 12 months]. In contrast, high dietary organic cyanogen intakes (1.5 mg
CN- /kg body wt/day in SE and C geographical areas) are associated with lower
hemoglobin S gene frequencies (2%; phenotypic incidence 4%), higher mean (+/- SD)
positive Plasmodium antibody titers (968.7 +/- 160.5), and a lower mean (+/- SEM)
prevalence of clinical falciparum malaria [1.73 times (+/- 0.11) within the
previous 12 months]. No other significant malaria-linked genetic variation exists
between regions or ethnic groups. Two evolutionary models are hypothesized to
suggest how 18 generations of differential dietary organic cyanogen intakes could
produce two distinct patterns of change in hemoglobin S gene frequencies,
modifying both the cadence and direction of evolution.
PMID- 28520194
TI - Basal metabolism of obese adolescents: Evidence for energy conservation compared
to normal and lean adolescents.
AB - To test if obese adolescents systematically conserve energy, comparisons of basal
metabolic rate (BMR) of obese, normal, and lean male and female adolescents were
made. Obese had eleevated values by as much as 23% (P <= 0.05) expressed as kJ .
24 hr-1 compared to the normal and lean. When indexed to body mass (kJ . kg-BM-1
. hr-1 ), the BMR for the obese was depressed by as much as -53% (P <= 0.01), and
when indexed to fat free mass (kJ . kg-FFM-1 . hr-1 ) it was depressed by -33%
compared to normal and lean adolescents. A "theoretical metabolic rate" (TMR),
based on the observed fat free mass, fat mass, and their thermal equivalents, was
proposed as a theoretical way to properly index basal metabolism, referenced to
body composition. Comparisons of the TMR between the obese, normal, and lean
revealed that the obese values were depressed by an average -22% (P <= 0.05). In
comparison, differences in TMR between the normal and lean males and females were
no larger than 8% (ns). It was concluded that since both the observed BMR
(expressed relative to body composition), and the derived TMR values were
depressed for the obese compared to the normal and lean adolescent, the data
suggest an energy saving hypothesis for obese adolescents.
PMID- 28520195
TI - Anthropometric somatotype of Bod girls: A comparison of high and low altitude
populations.
AB - The high altitude environment is known to influence the morphophysiology of man
in a variety of ways. Its possible impact on somatotype of adolescent girls has
not been investigated so far. For this purpose 348 female Bods, from 10 to 18
years old, have been somatotyped from high altitude (n = 176) of Ladakh (3,534 m)
and low altitude (n = 172) of Kullu Valley (1,500-2,200 m). The results of the
study reveal greater mesomorphy and ectomorphy in the high altitude Bod girls
than in ethnically similar low altitude Bod girls of comparable age. The study
has accorded the differences in the somatotypes to the high altitude stresses.
Striking similarities in boys and girls in terms of higher mesomorphy and
ectomorphy in the highlander Bods than the coeval lowlanders confirm the
hypothesis that the high altitude environment influences the somatotype
components.
PMID- 28520197
TI - Integrated Uncertainty Analysis for Ambient Pollutant Health Risk Assessment: A
Case Study of Ozone Mortality Risk.
AB - The U.S. Environmental Protection Agency (EPA) uses health risk assessment to
help inform its decisions in setting national ambient air quality standards
(NAAQS). EPA's standard approach is to make epidemiologically-based risk
estimates based on a single statistical model selected from the scientific
literature, called the "core" model. The uncertainty presented for "core" risk
estimates reflects only the statistical uncertainty associated with that one
model's concentration-response function parameter estimate(s). However,
epidemiologically-based risk estimates are also subject to "model uncertainty,"
which is a lack of knowledge about which of many plausible model specifications
and data sets best reflects the true relationship between health and ambient
pollutant concentrations. In 2002, a National Academies of Sciences (NAS)
committee recommended that model uncertainty be integrated into EPA's standard
risk analysis approach. This article discusses how model uncertainty can be taken
into account with an integrated uncertainty analysis (IUA) of health risk
estimates. It provides an illustrative numerical example based on risk of
premature death from respiratory mortality due to long-term exposures to ambient
ozone, which is a health risk considered in the 2015 ozone NAAQS decision. This
example demonstrates that use of IUA to quantitatively incorporate key model
uncertainties into risk estimates produces a substantially altered understanding
of the potential public health gain of a NAAQS policy decision, and that IUA can
also produce more helpful insights to guide that decision, such as evidence of
decreasing incremental health gains from progressive tightening of a NAAQS.
PMID- 28520196
TI - Environmentally Friendly Recycling of Fuel-Cell Membrane Electrode Assemblies by
Using Ionic Liquids.
AB - The platinum nanoparticles used as the catalyst in proton exchange membrane fuel
cells (PEMFCs) represent approximately 46 % of the total price of the cells for a
large-scale production, and this is one of the barriers to their
commercialization. Therefore, the recycling of the platinum catalyst could be the
best alternative to limit the production costs of PEMFCs. The usual recovery
routes for spent catalysts containing platinum are pyro-hydrometallurgical
processes in which a calcination step is followed by aqua regia treatment, and
these processes generate fumes and NOx emissions, respectively. The
electrochemical recovery route proposed here is more environmentally friendly,
performed under "soft" temperature conditions, and does not result in any gas
emissions. It consists of the coupling of the electrochemical leaching of
platinum in chloride-based ionic liquids (ILs), followed by its
electrodeposition. The leaching of platinum was studied in pure ILs and in ionic
liquid melts at different temperatures and with different chloride contents.
Through the modulation of the composition of the ionic-liquid melts, it is
possible to leach and electrodeposit the platinum from fuel-cell electrodes in a
single-cell process under an inert or ambient atmosphere.
PMID- 28520198
TI - Dynamic and steady-state oxygen-dependent lung relaxometry using inversion
recovery ultra-fast steady-state free precession imaging at 1.5 T.
AB - PURPOSE: To demonstrate the feasibility of oxygen-dependent relaxometry in human
lung using an inversion recovery ultra-fast steady-state free precession (IR
ufSSFP) technique. METHODS: Electrocardiogram-triggered pulmonary relaxometry
with IR-ufSSFP was performed in 7 healthy human subjects at 1.5 T. The data were
acquired under both normoxic and hyperoxic conditions. In a single breath-hold of
less than 9 seconds, 30 transient state IR-ufSSFP images were acquired, yielding
longitudinal (T1) and transversal (T2) relaxometry parameter maps using voxel
wise nonlinear fitting. Possible spatial misalignments between consecutive IR
ufSSFP parameter maps were corrected using elastic image registration.
Furthermore, dynamic relaxometry oxygen wash-in and wash-out scans were performed
in one volunteer. From this, T1 -related wash-in and wash-out time constants
(tauwi , tauwo ) were calculated voxel-wise on registered maps using an
exponential fitting model. RESULTS: For healthy lung, observed T1 values were
1399 +/- 77 and 1290 +/- 76 ms under normoxic and hyperoxic conditions,
respectively. Oxygen-related reduction of T1 was statistically significant in
every volunteer. No statistically significant change, however, was observed in
T2, with normoxic and hyperoxic T2 values of 55 +/- 16 and 56 +/- 17 ms,
respectively. The observed average tauwi was 87.0 +/- 28.7 seconds, whereas the
average tauwo was 73.5 +/- 21.6 seconds. CONCLUSION: IR-ufSSFP allows fast,
steady-state, and dynamic oxygen-dependent relaxometry of the human lung. Magn
Reson Med 79:839-845, 2018. (c) 2017 International Society for Magnetic Resonance
in Medicine.
PMID- 28520199
TI - Economic evaluation of strategies for restarting anticoagulation therapy after a
first event of unprovoked venous thromboembolism.
AB - : Essentials Correct duration of treatment after a first unprovoked venous
thromboembolism (VTE) is unknown. We assessed when restarting anticoagulation was
worthwhile based on patient risk of recurrent VTE. When the risk over a one-year
period is 17.5%, restarting is cost-effective. However, sensitivity analyses
indicate large uncertainty in the estimates. SUMMARY: Background Following at
least 3 months of anticoagulation therapy after a first unprovoked venous
thromboembolism (VTE), there is uncertainty about the duration of therapy.
Further anticoagulation therapy reduces the risk of having a potentially fatal
recurrent VTE but at the expense of a higher risk of bleeding, which can also be
fatal. Objective An economic evaluation sought to estimate the long-term cost
effectiveness of using a decision rule for restarting anticoagulation therapy vs.
no extension of therapy in patients based on their risk of a further unprovoked
VTE. Methods A Markov patient-level simulation model was developed, which adopted
a lifetime time horizon with monthly time cycles and was from a UK National
Health Service (NHS)/Personal Social Services (PSS) perspective. Results Base
case model results suggest that treating patients with a predicted 1 year VTE
risk of 17.5% or higher may be cost-effective if decision makers are willing to
pay up to L20 000 per quality adjusted life year (QALY) gained. However,
probabilistic sensitivity analysis shows that the model was highly sensitive to
overall parameter uncertainty and caution is warranted in selecting the optimal
decision rule on cost-effectiveness grounds. Univariate sensitivity analyses
indicate variables such as anticoagulation therapy disutility and mortality risks
were very influential in driving model results. Conclusion This represents the
first economic model to consider the use of a decision rule for restarting
therapy for unprovoked VTE patients. Better data are required to predict long
term bleeding risks during therapy in this patient group.
PMID- 28520202
TI - Haemophilia treatment for all and the role of tolerance, difference and
education.
PMID- 28520200
TI - Hepatic infiltration by silicone in a patient With ASIA syndrome.
PMID- 28520201
TI - Communication practices that encourage and constrain shared decision making in
health-care encounters: Systematic review of conversation analytic research.
AB - BACKGROUND: Shared decision making (SDM) is generally treated as good practice in
health-care interactions. Conversation analytic research has yielded detailed
findings about decision making in health-care encounters. OBJECTIVE: To map
decision making communication practices relevant to health-care outcomes in face
to-face interactions yielded by prior conversation analyses, and to examine their
function in relation to SDM. SEARCH STRATEGY: We searched nine electronic
databases (last search November 2016) and our own and other academics'
collections. INCLUSION CRITERIA: Published conversation analyses (no restriction
on publication dates) using recordings of health-care encounters in English where
the patient (and/or companion) was present and where the data and analysis
focused on health/illness-related decision making. DATA EXTRACTION AND SYNTHESIS:
We extracted study characteristics, aims, findings relating to communication
practices, how these functioned in relation to SDM, and internal/external
validity issues. We synthesised findings aggregatively. RESULTS: Twenty-eight
publications met the inclusion criteria. We sorted findings into 13 types of
communication practices and organized these in relation to four elements of
decision-making sequences: (i) broaching decision making; (ii) putting forward a
course of action; (iii) committing or not (to the action put forward); and (iv)
HCPs' responses to patients' resistance or withholding of commitment. Patients
have limited opportunities to influence decision making. HCPs' practices may
constrain or encourage this participation. CONCLUSIONS: Patients, companions and
HCPs together treat and undertake decision making as shared, though to varying
degrees. Even for non-negotiable treatment trajectories, the spirit of SDM can be
invoked through practices that encourage participation (eg by bringing the
patient towards shared understanding of the decision's rationale).
PMID- 28520203
TI - Subthalamic nucleus deep brain stimulation for Parkinson's disease in a patient
with severe haemophilia A.
PMID- 28520204
TI - Weekly recombinant FIX prophylaxis for severe haemophilia B in normal clinical
practice: data from UKHCDO and Finland.
PMID- 28520205
TI - SIPPET trial: the answers.
PMID- 28520206
TI - Time to review the way we estimate access to haemophilia concentrates worldwide.
PMID- 28520207
TI - Comparison of F13A1 gene mutations in 73 patients treated with recombinant FXIII
A2.
AB - INTRODUCTION: Congenital factor XIII (FXIII) deficiency is a rare, autosomal
recessive bleeding disorder usually caused by mutations in the F13A1 gene that
produce a severe quantitative (type I) deficiency of the FXIII-A subunit. AIM: To
determine the genotypes of patients with severe FXIII-A deficiency treated with
recombinant FXIII-A subunit (rFXIII-A2 ) participating in three international
efficacy and safety trials. METHODS: We determined the genotypes of 73 patients
in total; 32 had already undergone genotype analysis and were known to carry
F13A1 mutations that have been previously reported in the literature. Mutation
screening was performed in 41 patients with unknown genetic status using direct
sequencing. RESULTS: In total, 51 distinct mutations in 73 patients were
identified. Two patients showed a phenotype of severe FXIII-A deficiency, despite
having heterozygous missense mutations. Two siblings carried a missense mutation
in the F13A1 gene (p.Ser296Arg) in combination with a novel, probably polymorphic
variant of the F13B gene (p.Ser654Phe). Molecular modelling of five F13A1 novel
missense mutations (p.Leu171Phe, p.Glu204Lys, p.Leu276Phe, p.Asp405His and
p.Gly411Cys) predicted a damaging effect of these mutations on protein structure.
Although five patients treated with rFXIII-A2 had transient, low-titre, non
neutralizing anti-rFXIII antibodies, no patients developed FXIII-neutralizing
antibodies (inhibitors). CONCLUSION: The identified mutations are causally
implicated in severe FXIII deficiency; however, they do not appear to increase
the risk of neutralizing antibody development against rFXIII-A2 .
PMID- 28520208
TI - Coagulation abnormalities and haemostatic surgical outcomes in 142 patients with
Noonan syndrome.
PMID- 28520209
TI - Successful perioperative haemostatic management of aortic coarctation in a 5-week
old infant with severe haemophilia A.
PMID- 28520210
TI - Biases in the reporting of hepatocellular carcinoma tumor sizes on the liver
transplant waiting list.
AB - : We investigated the possibility that patients with hepatocellular carcinoma
(HCC) listed for liver transplant with tumors just outside stage T2 size criteria
may be inaccurately reported as just meeting the tumor size criteria for
transplant. The United Network for Organ Sharing/Standard Transplant Analysis and
Research database identified 12,958 patients listed for liver transplants with
HCC exception points from 2006 to 2013, 9,168 of whom were listed with one tumor.
A logistic power peak function was fitted to the single-tumor size histogram,
with the fitted values representing unbiased expected values. The difference
between the observed and expected tumor counts for 2.0 cm and 5.0 cm was 238
(22%) and 66 (57%), respectively. This suggests that up to 304 (3.0%) patients
with tumors outside of transplant criteria had their measurements recorded at the
margins of eligibility. A risk-adjusted Poisson model evaluated the ratio of
observed to expected HCC recurrence by tumor size. There were 435 HCC recurrences
among 6,049 transplants. Only 2.0-cm tumors had observed to expected recurrence
differing from 1 (ratio 0.73, 95% confidence interval 0.57-0.94), indicating a
27% lower than expected rate of recurrence. CONCLUSION: Higher than expected
observed tumor counts at the lower transplant criteria margin were corroborated
by lower than expected HCC recurrence, suggesting that tumor sizes at the margins
of HCC transplant criteria may be subject to inaccurate reporting. (Hepatology
2017;66:1144-1150).
PMID- 28520212
TI - Models for cutaneous wound healing.
PMID- 28520211
TI - Aging and Parkinson's disease: Different sides of the same coin?
AB - Despite abundant epidemiological evidence in support of aging as the primary risk
factor for PD, biological correlates of a connection have been elusive. In this
article, we address the following question: does aging represent biology
accurately characterized as pre-PD? We present evidence from our work on midbrain
dopamine neurons of aging nonhuman primates that demonstrates that markers of
known correlates of dopamine neuron degeneration in PD, including impaired
proteasome/lysosome function, oxidative/nitrative damage, and inflammation, all
increase with advancing age and are exaggerated in the ventral tier substantia
nigra dopamine neurons most vulnerable to degeneration in PD. Our findings
support the view that aging-related changes in the dopamine system approach the
biological threshold for parkinsonism, actively producing a vulnerable pre
parkinsonian state. (c) 2017 The Authors. Movement Disorders published by Wiley
Periodicals, Inc. on behalf of International Parkinson and Movement Disorder
Society.
PMID- 28520213
TI - The PNPLA3 variant associated with fatty liver disease (I148M) accumulates on
lipid droplets by evading ubiquitylation.
AB - : A sequence variation (I148M) in patatin-like phospholipase domain-containing
protein 3 (PNPLA3) is strongly associated with fatty liver disease, but the
underlying mechanism remains obscure. In this study, we used knock-in (KI) mice
(Pnpla3148M/M ) to examine the mechanism responsible for accumulation of
triglyceride (TG) and PNPLA3 in hepatic lipid droplets (LDs). No differences were
found between Pnpla3148M/M and Pnpla3+/+ mice in hepatic TG synthesis,
utilization, or secretion. These results are consistent with TG accumulation in
the Pnpla3148M/M mice being caused by impaired TG mobilization from LDs. Sucrose
feeding, which is required to elicit fatty liver in KI mice, led to a much larger
and more persistent increase in PNPLA3 protein in the KI mice than in wild-type
(WT) mice. Inhibition of the proteasome (bortezomib), but not macroautophagy (3
methyladenine), markedly increased PNPLA3 levels in WT mice, coincident with the
appearance of ubiquitylated forms of the protein. Bortezomib did not increase
PNPLA3 levels in Pnpla3148M/M mice, and only trace amounts of ubiquitylated
PNPLA3 were seen in these animals. CONCLUSION: These results are consistent with
the notion that the 148M variant disrupts ubiquitylation and proteasomal
degradation of PNPLA3, resulting in accumulation of PNPLA3-148M and impaired
mobilization of TG from LDs. (Hepatology 2017;66:1111-1124).
PMID- 28520214
TI - mTORC1 Inhibits NF-kappaB/NFATc1 Signaling and Prevents Osteoclast Precursor
Differentiation, In Vitro and In Mice.
AB - The mechanistic target of rapamycin complex 1 (mTORC1) is a critical sensor for
bone homeostasis and bone formation; however, the role of mTORC1 in osteoclast
development and the underlying mechanisms have not yet been fully established.
Here, we found that mTORC1 activity declined during osteoclast precursors
differentiation in vitro and in vivo. We further targeted deletion of Raptor
(mTORC1 key component) or Tsc1 (mTORC1 negative regulator) to constitutively
inhibit or activate mTORC1 in osteoclast precursors (monocytes/macrophages),
using LyzM-cre mice. Osteoclastic formation was drastically increased in cultures
of Raptor deficient bone marrow monocytes/macrophages (BMMs), and Raptor
deficient mice displayed osteopenia with enhanced osteoclastogenesis. Conversely,
BMMs lacking Tsc1 exhibited a severe defect in osteoclast-like differentiation
and absorptive function, both of which were restored following rapamycin
treatment. Importantly, expression of nuclear factor kappa-light-chain-enhancer
of activated B cells (NF-kappaB) and nuclear factor of activated T cells,
cytoplasmic 1 (NFATc1), transcription factors that are essential for osteoclast
differentiation was negatively regulated by mTORC1 in osteoclast lineages. These
results provide evidence that mTORC1 plays as a critical role as an osteoclastic
differentiation-limiting signal and suggest a potential drawback in treating bone
loss-related diseases with mTOR inhibitors clinically. (c) 2017 American Society
for Bone and Mineral Research.
PMID- 28520216
TI - Evaluation of Prediction of Polymorphisms of DNA Repair Genes on the Efficacy of
Platinum-Based Chemotherapy in Patients With Non-Small Cell Lung Cancer: A
Network Meta-Analysis.
AB - This network meta-analysis (NMA) was conducted to compare the predictive value of
14 SNPs in eight DNA repair genes on the efficacy of platinum-based chemotherapy
in patients with non-small cell lung cancer (NSCLC). These included ERCC1
(rs11615, rs3212986, rs3212948), XRCC1 (rs25487, rs25489, rs1799782), XPD
(rs13181, rs1799793), XPG (rs1047768, rs17655), XPA (rs1800975), XRCC3
(rs861539), APE1 (rs3136820), and RRM1 (rs1042858). The PubMed and Cochrane
library databases were reviewed from their inception to February 2017 and studies
which met our inclusion criteria were included in our investigation. This network
meta-analysis combines direct and indirect evidence to assess the predictive
value of 14 SNPs in eight DNA repair genes on the efficacy of platinum-based
chemotherapy in NSCLC. We evaluated the predictive value through the use of the
odd ratios (OR) and drawing surface under the cumulative ranking curves (SUCRA).
A total of 26 eligible cohort studies were enrolled in this NMA. The pairwise
meta-analysis indicated that in terms of overall response ratio (ORR), ERCC1
(rs11615), XRCC1 (rs25487, rs1799782), and XPD (rs13181) polymorphisms are
associated with the efficacy of platinum-based chemotherapy in NSCLC. The result
of this NMA suggests that there is no significant difference in predictive value
of 8 DNA repair genes on the efficacy of platinum-based chemotherapy in NSCLC
patients. The rank of SUCRA values of the 14 SNPs in the eight DNA repair genes
were: XPD (rs1799793)->ERCC1 (rs3212986)->XPA(rs1800975)->ERCC1(rs3212948)
>XRCC1(rs25487)->XRCC3(rs861539)->APE1(rs3136820)->ERCC1(rs11615)
>XRCC1(rs1799782)->RRM1(rs1042858)->XPD(rs13181)->XPG (rs1047768)->XPG(rs17655)
>XRCC1(rs25489). ERCC1(rs11615), XRCC1(rs25487, rs1799782) and XPD(rs13181)
polymorphisms were better predictors in evaluating the efficacy of platinum-based
chemotherapy in NSCLC patients. J. Cell. Biochem. 118: 4782-4791, 2017. (c) 2017
Wiley Periodicals, Inc.
PMID- 28520215
TI - Aspirin and the risk of cardiovascular events in atherosclerosis patients with
and without prior ischemic events.
AB - BACKGROUND: The benefit of aspirin among patients with stable atherosclerosis
without a prior ischemic event is not well defined. HYPOTHESIS: Aspirin would be
of benefit in outpatients with atherosclerosis with prior ischemic events, but
not in those without ischemic events. METHODS: Subjects from the Reduction of
Atherothrombosis for Continued Health registry were divided according to prior
ischemic event (n =21 724) vs stable atherosclerosis, but no prior ischemic event
(n = 11 872). Analyses were propensity score matched. Aspirin use was updated at
each clinic visit and considered as a time-varying covariate. The primary outcome
was the first occurrence of cardiovascular death, myocardial infarction, or
stroke. RESULTS: In the group with a prior ischemic event, aspirin use was
associated with a marginally lower risk of the primary outcome at a median of 41
months (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.65-1.01, P =
0.06). In the group without a prior ischemic event, aspirin use was not
associated with a lower risk of the primary outcome at a median of 36 months (HR:
1.03, 95% CI: 0.73-1.45, P = 0.86). CONCLUSIONS: In this observational analysis
of outpatients with stable atherosclerosis, aspirin was marginally beneficial
among patients with a prior ischemic event; however, there was no apparent
benefit among those with no prior ischemic event.
PMID- 28520218
TI - Lithium Bond Chemistry in Lithium-Sulfur Batteries.
AB - The lithium-sulfur (Li-S) battery is a promising high-energy-density storage
system. The strong anchoring of intermediates is widely accepted to retard the
shuttle of polysulfides in a working battery. However, the understanding of the
intrinsic chemistry is still deficient. Inspired by the concept of hydrogen bond,
herein we focus on the Li bond chemistry in Li-S batteries through sophisticated
quantum chemical calculations, in combination with 7 Li nuclear magnetic
resonance (NMR) spectroscopy. Identified as Li bond, the strong dipole-dipole
interaction between Li polysulfides and Li-S cathode materials originates from
the electron-rich donors (e.g., pyridinic nitrogen (pN)), and is enhanced by the
inductive and conjugative effect of scaffold materials with pi-electrons (e.g.,
graphene). The chemical shift of Li polysulfides in 7 Li NMR spectroscopy, being
both theoretically predicted and experimentally verified, is suggested to serve
as a quantitative descriptor of Li bond strength. These theoretical insights were
further proved by actual electrochemical tests. This work highlights the
importance of Li bond chemistry in Li-S cell and provides a deep comprehension,
which is helpful to the cathode materials rational design and practical
applications of Li-S batteries.
PMID- 28520217
TI - The gene encoding the inwardly rectifying potassium channel Kir4.1 may be
involved in sudden infant death syndrome.
AB - AIM: Disturbances in brain function and development may play a role in sudden
infant death syndrome (SIDS). This Norwegian study aimed to test the hypothesis
that specific variants of genes involved in water transport and potassium
homeostasis would be predisposing factors for SIDS. METHODS: Genetic variation in
the genes encoding aquaporin-4 (AQP4), Kir4.1 (KCNJ10) and alpha-syntrophin was
analysed in 171 SIDS cases (62.6% male) with a median age of 15.5 (2-52) weeks
and 398 adult controls (70.6% male) with a median age of 44 (11-91) years. All
the subjects were Caucasians who were autopsied from 1988 to 2013. RESULTS: The
CC genotype of rs72878794 in the AQP4 gene and a combination of the CC genotype
in rs17375748, rs1130183, rs12133079 and rs1186688 in KCNJ10 (4xCC) were found to
be associated with SIDS. The SIDS cases with the 4xCC SNP combination were
younger than the SIDS cases with other genotype combinations (p = 0.006).
CONCLUSION: This study indicates that genetic variations in KCNJ10 and AQP4 may
be predisposing factors for SIDS. Alterations in the expression of the
AQP4/Kir4.1 complex can disrupt water and ion homeostasis, which may influence
brain development and facilitate brain oedema formation This may be especially
unfavourable during the first weeks of life.
PMID- 28520219
TI - Plasminogen Activator Inhibitor Type-1 as a Regulator of Fibrosis.
AB - Fibrosis is known as a frequent and irreversible pathological condition which is
associated with organ failure. Tissue fibrosis is a central process in a variety
of chronic progressive diseases such as diabetes, hypertension, and persistent
inflammation. This state could contribute to chronic injury and the initiation of
tissue repair. Fibrotic disorders represent abnormal wound healing with defective
matrix turnover and clearance that lead to excessive accumulation of
extracellular matrix components. A variety of identified growth factors,
cytokines, and persistently activated myofibroblasts have critical roles in the
pathogenesis of fibrosis. Irrespective of etiology, the transforming growth
factor-beta pathway is the major driver of fibrotic response. Plasminogen
activator inhibitor-1 (PAI-1) is a crucial downstream target of this pathway.
Transforming growth factor-beta positively regulates PAI-1 gene expression via
two main pathways including Smad-mediated canonical and non-canonical pathways.
Overexpression of PAI-1 reduces extracellular matrix degradation via perturbing
the plasminogen activation system. Indeed, elevated PAI-1 levels inhibit
proteolytic activity of tissue plasminogen activator and urokinase plasminogen
activator which could contribute to a variety of inflammatory elements in the
injury site and to excessive matrix deposition. This review summarizes the
current knowledge of critical pathways that regulate PAI-1 gene expression and
suggests effective approaches for the treatment of fibrotic disease. J. Cell.
Biochem. 119: 17-27, 2018. (c) 2017 Wiley Periodicals, Inc.
PMID- 28520220
TI - Endothelial damage effects of circulating microparticles from patients with
stable angina are reduced by aspirin through ERK/p38 MAPKs pathways.
AB - INTRODUCTION: Platelet activation participates in the development of both
coronary artery disease (CAD) and circulating microparticles (MPs). As a commonly
used medicine for coronary heart disease, whether aspirin affects the function of
MPs remains unclear. AIMS: This study was designed to test MPs from healthy
subjects, and stable angina (SA) patients before and after aspirin administration
were obtained. MPs origins were tested by flow cytometry. Rat thoracic aortas
were incubated with MPs (with or without aspirin) to determine the effects of MPs
on expression of ERK1/2, JNKs, and p38 MAPK. Affect on levels of NF-kappaB, VCAM
1, NO, and O2-. RESULTS: Compared with healthy subjects, MPs concentrations
increased in SA patients, but decreased after aspirin administration. According
to flow cytometry, aspirin mainly decreased platelet-derived MP. MPs from SA
patients decreased the expression of ERK1/2, increased expression of p38 MAPKs,
JNKs. Increased NF-kappaB, VCAM-1, and (O2-) levels decreased NO content. Aspirin
therapy significantly inhibited function of MPs from SA patients, and pathway
inhibitors (ERK1/2 inhibitor PD98059, p38 MAPKs inhibitor SB203580, NF-kB
inhibitor PDTC) show similar effects with aspirin. CONCLUSION: These results
indicate that the pro-inflammatory, oxidative stress, procoagulant, and adhesion
properties of MPs can be partly blocked by aspirin via the ERK-NO/O2- and p38 -NF
kappaB-VCAM-1 signal pathway, which clarified other functions beyond anti
atherothrombotic of aspirin.
PMID- 28520223
TI - Evolution of infectious disease: A biocultural analysis of AIDS.
AB - The evolution of infectious disease can be understood from an ecological model
that incorporates information from anthropology, epidemiology, and biomedicine.
This model considers variables such as the pathogen, the host population, and the
environment. In this model, the role that culture as well as other environmental
variables plays in the transmission of infectious disease in human populations is
considered. In addition, the sociocultural response and its impact on the disease
process can be analyzed. The present AIDS epidemic is placed in an ecological and
evolutionary context of the disease in hominid evolution. The interaction between
Human Immunodeficiency Virus (HIV) and human populations is considered in this
perspective. The ability of the virus to survive in semen and blood both
increases as well as limits the possibility of transmission. Cultural practices
that increase the transmission of blood and semen or increase sexual activity
will obviously increase the potential risk of viral transmission. In societies
that practice exchange of blood, blood transfusion, and where vaccinations with
unclean needles exist or where there is intravenous (IV) drug use, the
transmission of HIV by blood is enhanced. HIV which can cause a breakdown of the
immunological system is paradoxically a very fragile pathogen. Replication occurs
within T-cells, an important part of the immunological system. Outside of the
blood or semen the virus dies quickly. From the perspective of the pathogen's
adaptation, the virus has effectively solved the problem of survival. The fragile
virus's long incubation period and its ability to survive in the presence of
antibodies help to assure its transmission. HIV's ability to suppress the
immunological system may assure its immediate survival, but this adaptation may
cause the death of its host from other opportunistic pathogens that are usually
not lethal.
PMID- 28520222
TI - High prevalence of human T-lymphotropic virus type I infection in isolated
populations of the Western Pacific region confirmed by Western immunoblot.
AB - High prevalences of antibodies against human T-lymphotropic virus type I (HTLV
I), as confirmed by Western immunoblot, were found in several remote indigenous
populations of the Solomon Islands and Vanuatu and in some isolated populations
of New Guinea that had no contact with Japanese or Africans and little contact
with Caucasians prior to our bleedings. By contrast, zero or very low prevalences
of HTLV-I infection were found in Guamanians and Carolinians, despite more than
30 years of intense contact with the Japanese. A total of 1,601 sera, collected
between 1963 and 1981 from 21 population groups in the Western Pacific, was
tested by enzyme-linked immunosorbent assay (ELISA) for IgG antibodies to HTLV-I.
By ELISA, prevalences of antibodies against HTLV-I ranged from zero to 50%.
Seropositivity could be confirmed in only 12.5% of 48 ELISA-positive sera
selected for testing by Western immunoblot. However, the confirmed HTLV-I
seroprevalences in some Melanesian populations were still as high as those found
in HTLV-I-endemic regions, such as southwestern Japan and the Caribbean basin.
HTLV-I prevalences were similar among males and females, and acquisition of
antibodies increased with age. Our data indicate that infections with HTLV-I or a
related retrovirus have been widespread in the southwestern Pacific for over 25
year in populations with minimal outside contact, while some populations which
had extensive Japanese contact have no evidence of infection. Furthermore, based
on the high frequency of indeterminate Western immunoblots, we conclude that in
Melanesia this may represent either incomplete specific reactivity to HTLV-I or
the existence of an antigenic variant of HTLV-I, distinct from prototype
Japanese, American, and European HTLV-I strains.
PMID- 28520224
TI - Environmental context, social interactions, and the spread of HIV.
AB - The spread of HIV through a population is influenced by many factors. These
include the frequency and type of sexual activity, age distribution of the
population, use of intravenous drugs and behaviors associated with their use, the
pattern of infectivity of the virus during the several stages of the infection,
geographic location, and the patterns of interaction among individuals and the
context in which those interactions occur. A number of questions about the
natural history and epidemiology of AIDS remain unanswered. Since the disease has
only recently been recognized, historical data are unavailable to aid in
answering these questions. Mathematical models provide one approach that can be
of use in understanding the spread of the disease. Because of the complexity of
the biology and epidemiology of AIDS, useful models must focus on specific
aspects of the disease. In addition to a brief review of existing models for the
spread of AIDS, a new model which incorporates the effects of social context
operating at the time of a sexual encounter is described. The model considers the
spread of the disease in a population of homosexual men divided into groups based
on relative risk for the disease. Individuals are assigned to a specific group on
the basis of their normal sexual activities, but they may take on the
characteristics of a different risk group temporarily given the conditions
operating when they engage in a sexual encounter. Results from preliminary
analyses of the new model indicate that the major effects of incorporating social
context include a decrease in the number of cases of the disease, sometimes by an
order of magnitude or more, delayed spread of the disease, and a decreased impact
of the disease on low and medium risk groups.
PMID- 28520225
TI - Human T-lymphotropic virus type I: A retrovirus causing chronic myeloneuropathies
in tropical and temperate climates.
AB - Human T-cell lymphotropic virus type I (HTLV-I), the first human retrovirus to be
isolated, is the cause of endemic tropical spastic paraparesis (TSP). Originally,
this chronic neurological disorder was described as a disease seen among blacks
of low socioeconomic status living in tropical countries, and thus for many
decades TSP remained a little known curiosity outside the endemic regions. The
link between HTLV-I infection and TSP was made fortuitously, when antibodies to
HTLV-I were found in serum and cerebrospinal fluid of TSP patients in Jamaica,
Colombia, and Martinique. Soon thereafter a similar disorder, designated HTLV-I
associated myelopathy (HAM), was reported from southern Japan. This broadened the
geographic and ethnic boundaries of this chronic myelopathy and the disease has
now been reported in multiple ethnic groups from more than 40 countries, in both
tropical and temperate regions. The name TSP/HAM is now used to include all
patients (regardless of race or country of origin) who have HTLV-I-positive
endemic TSP or HAM.
PMID- 28520226
TI - Raymond Pearl memorial lecture, 1989: Cultural practices as determinants of
clinical pathology and epidemiology of venereal infections: Implications for
predictions about the AIDS epidemic.
AB - Sexually transmitted diseases newly introduced into diverse primitive and
isolated populations have behaved differently in clinical severity and
seriousness of the epidemics they have caused, because of culturally different
sexual practices. Epidemic interstitial plasma cell pneumonia in the 1930s-1950s
in eastern and northern Europe, caused by Pneumocystis carinii and accompanied by
cytomegalovirus infection, was an unexpected AIDS-like epidemic which spread
slowly, then quickly and inexplicably disappeared. Newly recognized endemic HTLV
I and epidemic HIV human retrovirus infections are behaving in a fashion
similarly difficult to anticipate and predict.
PMID- 28520221
TI - Rap1b Is an Effector of Axin2 Regulating Crosstalk of Signaling Pathways During
Skeletal Development.
AB - Recent identification and isolation of suture stem cells capable of long-term
self-renewal, clonal expanding, and differentiating demonstrate their essential
role in calvarial bone development, homeostasis, and injury repair. These bona
fide stem cells express a high level of Axin2 and are able to mediate bone
regeneration and repair in a cell autonomous fashion. The importance of Axin2 is
further demonstrated by its genetic inactivation in mice causing skeletal
deformities resembling craniosynostosis in humans. The fate determination and
subsequent differentiation of Axin2+ stem cells are highly orchestrated by a
variety of evolutionary conserved signaling pathways including Wnt, FGF, and BMP.
These signals are often antagonistic of each other and possess differential
effects on osteogenic and chondrogenic cell types. However, the mechanisms
underlying the interplay of these signaling transductions remain largely elusive.
Here we identify Rap1b acting downstream of Axin2 as a signaling interrogator for
FGF and BMP. Genetic analysis reveals that Rap1b is essential for development of
craniofacial and body skeletons. Axin2 regulates Rap1b through modulation of
canonical BMP signaling. The BMP-mediated activation of Rap1b promotes
chondrogenic fate and chondrogenesis. Furthermore, by inhibiting MAPK signaling,
Rap1b mediates the antagonizing effect of BMP on FGF to repress osteoblast
differentiation. Disruption of Rap1b in mice not only enhances osteoblast
differentiation but also impairs chondrocyte differentiation during
intramembranous and endochondral ossifications, respectively, leading to severe
defects in craniofacial and body skeletons. Our findings reveal a dual role of
Rap1b in development of the skeletogenic cell types. Rap1b is critical for
balancing the signaling effects of BMP and FGF during skeletal development and
disease. (c) 2017 American Society for Bone and Mineral Research.
PMID- 28520227
TI - AIDS in Africa: A bioanthropological perspective.
AB - The epidemiological characteristics of acquired immunodeficiency syndrome (AIDS)
in Africa are reviewed. Infection rates with human immunodeficiency virus 1 (HIV
1) and human immunodeficiency virus 2 (HIV-2) vary across the continent of Africa
with the highest infection rates occurring in East and Central Africa. The
primary pattern of infection with HIV-1 is characterized by high rates of
heterosexual vs. homosexual transmission, a low male to female sex ratio of
cases, and high rates of pediatric AIDS. Cultural anthropologists have emphasized
variation in human sexual behavior as an important factor in understanding the
HIV epidemic. These studies have focussed on understanding the range of sexual
risk behaviors present in different cultures and the cultural meanings of these
behaviors. Biological anthropologists approach the study of human disease with an
interest in human biological variation, evolutionary models, and the interface
between biology and behavior. A Bioanthropology Research Agenda for AIDS is
proposed which focuses on these three areas. Potential research domains for
biological anthropologists include: human biological variation and cofactors of
infection and disease, the evolutionary impact of HIV infection, and the
interface between biology and behavior and the biological impact of behavior.
Working with colleagues in other disciplines, biological anthropologists can
assist in furthering understanding of the variables of HIV infection and disease.
PMID- 28520228
TI - Introduction: Biocultural implications of AIDS and other retroviral disorders.
PMID- 28520229
TI - Epidemiology and clinical picture of human immunodeficiency virus type 1
infection and the acquired immune deficiency syndrome.
AB - Human Immunodeficiency Virus Type 1 (HIV-1) infection which causes the terminal
Acquired Immune Deficiency Syndrome (AIDS) is one of the major new pandemics of
this millenium. This infection is believed to be a zoonosis which achieved
sustained transmission among humans because of recent increases in sexual
promiscuity and needle-sharing drug use. Although the HIV-1 epidemic is of
relatively recent onset, its modes of transmission have been clearly defined:
sexual relations, blood injection, and childbirth. Other possible transmission
methods such as non-sexual social interaction and insects have been explicitly
excluded. Susceptibility is increased by genital ulcers and lack of male
circumcision but probably not by genetic factors or female circumcision.
Transmissibility is also increased by genital ulcers and, more importantly, by
the stage of disease. Progression by stages to fatal diseases will probably occur
in most, if not all, infected individuals, usually within a decade. While HIV-1
has a direct effect on the intestinal track and the central nervous system, its
primary effect is suppression of the immune system resulting in overwhelming
secondary infections and, less clearly, cancers. Human Immunodeficiency Virus
Type 1 infection is incurable and is likely to remain so for the foreseeable
future. Although life-prolonging treatments have been developed, a vaccine will
likely not be available in the foreseeable future. Like most previous new
epidemic diseases, HIV-1 infection is being and will continue to be modified by
changing human behavior patterns.
PMID- 28520230
TI - Perspective: Human immunodeficiency virus infection in children.
AB - Epidemiologic studies indicate that the number of women and children with human
immunodeficiency virus (HIV) infection will continue to increase in the next
decade. The impact of this aspect of the AIDS pandemic, including increased
infant mortality, will be greatest in developing nations. The biologic properties
of HIV, a lentivirus, complicate the strategies to alter the course of the
pandemic. A long asymptomatic interval between initial infection and the onset of
clinical disease, the ability of HIV to evade immune clearance, and the
propensity for rapid mutation and selection of viral variants all favor survival
of the virus over the host.
PMID- 28520231
TI - Lymphocyte alloantigenic challenge as a potential cofactor in HIV infection and
progression to AIDS.
AB - A hypothesis is developed that circulatory exposure to alloantigens found on
lymphocytes triggers a series of events leading to suppression of the cell
mediated arm of the immune system and, therefore, that such alloantigenic
challenge can be an important cofactor promoting infection with the human
immunodeficiency virus (HIV) and development of the acquired immunodeficiency
syndrome (AIDS) following infection. The explanatory model that is developed is
based in large part on current knowledge of the results of fetal lymphocyte
alloantigenic challenge of the maternal immune system. It is our contention that
the maternal response which leads to suppression of cell-mediated immunity is a
mechanism promoting survival of the fetal "allograft," and that this mechanism is
an evolutionary adaptation in humans and other placental mammals. We also
hypothesize that circulatory exposure to these same alloantigens leads to an
immunosuppressive state which enhances survival of HIV in an exposed individual
and augments the immunosuppressive action of HIV in promoting progression to
clinical AIDS. Findings from studies of individuals who are at risk for exposure
to lymphocyte alloantigenic challenge and from HIV infected patients are reviewed
and discussed in light of this hypothesis.
PMID- 28520232
TI - Human iPSC-MSC-Derived Xenografts Modulate Immune Responses by Inhibiting the
Cleavage of Caspases.
AB - Mesenchymal stem cells (MSCs) negatively modulate immune properties. Induced
pluripotent stem cells (iPSCs)-derived MSCs are alternative source of MSCs.
However, the effects of iPSC-MSCs on T cells phenotypes in vivo remain unclear.
We established an iPSC-MSC-transplanted host versus graft reaction mouse model
using subcapsular kidney injection. Th1, Th2, regulatory T cells (Treg), and Th17
phenotypes and their cytokines were investigated in vivo and in vitro. The role
of caspases and the soluble factors involved in the effects of MSCs were
examined. We found that iPSC-MSC grafts led to more cell survival and less
infiltration of inflammatory cells in mice. iPSC-MSC transplantation inhibited T
cell proliferation, decreased Th1 and Th2 phenotypes and cytokines, upregulated
Th17 and Treg subsets. Moreover, iPSC-MSCs inhibited the cleavage of caspases 3
and 8 and inhibition of caspases downregulated Th1, Th2 responses and upregulated
Th17, Treg responses. Soluble factors were determined using protein array and TGF
beta1/2/3, IL-10, and MCP-1 were found to be highly expressed in iPSC-MSCs. The
administration of the soluble factors decreased Th1/2 response, upregulated Treg
response and inhibited the cleavage of caspases. Our results demonstrate that
iPSC-MSCs regulate T cell responses as a result of a combined action of the above
soluble factors secreted by iPSC-MSCs. These factors suppress T cell responses by
inhibiting the cleavage of caspases. These data provide a novel immunomodulatory
mechanism for the underlying iPSC-MSC-based immunomodulatory effects on T cell
responses. Stem Cells 2017;35:1719-1732.
PMID- 28520235
TI - First Principles Neural Network Potentials for Reactive Simulations of Large
Molecular and Condensed Systems.
AB - Modern simulation techniques have reached a level of maturity which allows a wide
range of problems in chemistry and materials science to be addressed.
Unfortunately, the application of first principles methods with predictive power
is still limited to rather small systems, and despite the rapid evolution of
computer hardware no fundamental change in this situation can be expected.
Consequently, the development of more efficient but equally reliable atomistic
potentials to reach an atomic level understanding of complex systems has received
considerable attention in recent years. A promising new development has been the
introduction of machine learning (ML) methods to describe the atomic
interactions. Once trained with electronic structure data, ML potentials can
accelerate computer simulations by several orders of magnitude, while preserving
quantum mechanical accuracy. This Review considers the methodology of an
important class of ML potentials that employs artificial neural networks.
PMID- 28520234
TI - Bullous pemphigoid associated with dipeptidyl peptidase-4 inhibitors: A report of
five cases.
AB - Bullous pemphigoid (BP) is an autoimmune blistering skin disorder. Recently, BP
induced by dipeptidyl peptidase-4 (DPP-4) inhibitors has been a concern. Although
DPP-4 inhibitors are commonly used in the Asian population because of their
safety and efficacy, BP associated with DPP-4 inhibitors is sometimes seen in
clinical settings. Here, we report five Japanese cases of BP associated with the
agents. In the present cases, BP occurred in older adults using four different
DPP-4 inhibitors, which showed various clinical manifestations in terms of
latency period for BP, sex, glycemic control and diabetes duration. Withdrawal of
DPP-4 inhibitors was effective in improving BP, and achieved remission even in
cases requiring oral steroid administration and intravenous immunoglobulin
therapy. Clinicians should note the importance of early diagnosis of this
clinical condition and initiate prompt withdrawal of DPP-4 inhibitors.
PMID- 28520233
TI - A Nanojunction Polymer Photoelectrode for Efficient Charge Transport and
Separation.
AB - A metal-free photoanode nanojunction architecture, composed of B-doped carbon
nitride nanolayer and bulk carbon nitride, was fabricated by a one-step approach.
This type of nanojunction (s-BCN) overcomes a few intrinsic drawbacks of carbon
nitride film (severe bulk charge recombination and slow charge transfer). The top
layer of the nanojunction has a depth of ca. 100 nm and the bottom layer is ca.
900 nm. The nanojunction photoanode results into a 10-fold higher photocurrent
than bulk graphitic carbon nitride (G-CN) photoanode, with a record photocurrent
density of 103.2 MUA cm-2 at 1.23 V vs. RHE under one sun irradiation and an
extremely high incident photon-to-current efficiency (IPCE) of ca. 10 % at 400
nm. Electrochemical impedance spectroscopy, Mott-Schottky plots, and intensity
modulated photocurrent spectroscopy show that such enhancement is mainly due to
the mitigated deep trap states, a more than 10 times faster charge transfer rate
and nearly three times higher conductivity due to the nanojunction architecture.
PMID- 28520236
TI - Analysis of amino acids using serially coupled columns.
AB - Single conventional columns in reversed-phase liquid chromatography are
insufficient for analysing the isoindoles of primary amino acids due to their
limited functionality. An interesting possibility for increasing the separation
power is the combination of several columns of different nature, where the length
is modified by coupling small segments. This approach may require a considerable
investment to have multiple lengths for each stationary phase. However, the
combination of only two columns of fixed length can be enough to resolve
satisfactorily relatively complex mixtures, provided that an optimised gradient
program is applied. In this work, a mixture of 19 primary amino acid isoindoles
found in proteins was analysed. Four stationary phases were assayed: C18,
pentafluorophenyl-C18, C4 and cyano. The mixture of isoindoles was successfully
resolved in practical times using a pentafluorophenyl-C18 column coupled to a C4
column, in spite of the extremely poor performance obtained when each column is
used isolatedly, independently of the length. The extreme diversity in the
polarities of the isoindoles and the need of extrapolating the retention
behaviour in certain regions of the solvent content domain makes the modelling of
the retention behaviour of the isoindoles particularly difficult. Nevertheless,
the predicted optimal separations were very satisfactory.
PMID- 28520237
TI - Phylogenies and the forces of evolution.
AB - The construction of phylogenetic trees from gene frequency data assumes that a
history of binary fissioning of populations has been the major cause of genetic
variation. However, in many areas of the world human populations have been
relatively stable with local gene flow. This population history is closer to an
isolation by distance model. It was modelled by a simulation of gene frequency
changes in a linear sequence of 50 stable populations with gene flow among
neighboring populations. Phylogenetic trees were constructed from the gene
frequencies after the simulation was run for 500 generations. Using only a few
loci there is little correlation between genetic and geographic distance, but
with 40 or more loci, there was a perfect correlation with geographic distance. A
different population model can thus result in a phylogenetic tree comparable to
those assumed to be produced by binary fission.
PMID- 28520238
TI - Biological variability in a migrating isolate, the Tokelau Islands: Child growth
in different environments.
AB - The magnitude and rates of growth have been compared among two cross-sectional
samples of Tokelau children on the basis of 26 anthropometric dimensions. One of
the samples consisted of children living on the Tokelau Islands. The migrant
sample consisted of children of Tokelau descent who were living in New Zealand.
The comparison between samples suggest significant differences in the rate of
linear growth at the younger ages. However, most differences were not significant
among 17 year olds. The results support the hypothesis that even when the
original environment is favorable, qualitative changes in the environment may
affect the general pattern of growth. The effects of an accelerated growth
pattern cannot be determined at this time.
PMID- 28520239
TI - Relationship between population density and rates of injury mortality in New York
State (exclusive of New York City), 1978-1982.
AB - The relationship between population density and rates of mortality from
unintentional and intentional injuries is examined using mortality data from New
York State (exclusive of New York City), 1978-1982. Records for 26,118
individuals with an underlying cause of death due to injury were assigned to
population density quintiles based on residence of decedent at time of death.
Mortality rates for each population density quintile were examined separately by
sex and for 11 causes of injury death. Overall, injury mortality is highest in
the most rural and most urban populations. For both sexes, there is an inverse
relationship between mortality from motor vehicle incidents and population
density, and a positive relationship between homicide and population density.
Male mortality from unintentional poisoning deaths shows a positive relationship
with population density. Male mortality from fires shows a U-shaped relatinship
with population density, with the highest mortality in the most rural and most
urban populations. The relationships observed here between injury mortality and
population density are most likely due to concomitant variation with aspects of
the physical and cultural environments, such as socioeconomic status, ethnicity,
and individual risk behaviors.
PMID- 28520240
TI - The effect of height on family income.
AB - The effect of height on earnings of adult males sampled in the second National
Health and Nutrition Examination Survey, 1976-1980, was examined. Data were
collected using the multistage probability sampling method. Information was
available on medical history, physical examination, anthropometric dimensions,
diet, and sociodemographic characteristics. Complete information was available on
4,563 males, aged 20-65 years. The correlation between family income and height
was low (r = 0.13, P = 0.001). There was a secular trend for increasing mean
height over time, so that younger individuals were taller than older ones even
after correction for the decrease in stature caused by aging. After stratifying
by age and race, education and marital status, but not height, were significantly
associated with total family income. The weight-height ratio was significantly
related to income of Whites but not of nonwhites. White males in the highest
income category were significantly taller, heavier, more adipose, had higher
levels of education, and were more often married than were their lowest income
white counterparts. Among nonwhites, marital status and education alone
differentiated highest from lowest income nonwhite males. Thus, at least for
White males, appearance, that is, adiposity, together with education and marital
status, are major factors relating to income.
PMID- 28520242
TI - Brief Review.
PMID- 28520241
TI - The reliability of recalled estimates of menarcheal age in a sample of older
women.
AB - The accuracy of recalled age at first menses has been questioned, particularly if
subjects are relatively old. This paper illustrates the use of a statistical
technique that quantifies the reliability of recalled age at menarche based on re
interview of a small (15-20) subsample of subjects. Menarcheal age collected with
the retrospective method in a sample of 108 females, 50 years of age and older,
from Limon, Costa Rica, is reliable.
PMID- 28520243
TI - Infertility in Herero pastoralists of southern Africa.
AB - Transition from low to high rates of fertility among Herero pastoralists of the
northern Kalahari of Botswana is examined. Total fertility rates have increased
from 2.65 in the first half of this century to 7.02 in the last decade, while
postreproductive women report having had only 3.47 births. We use an indirect
estimator of the fertility of mothers to show that the Herero have been afflicted
with abnormally low fertility since early in this century. Although the several
possible causes of subfertility in this population, including disease, maternal
health, and child care practices are examined, it is concluded that the effects
of venereal diseases are most likely responsible for abnormally low fertility.
The dramatic increase in fertility following treatment of a major cause of
infertility underscores the potential impact diseases may have on human
reproductive patterns. This study is the first to document subfertility in an
ethnic group of southern Africa.
PMID- 28520244
TI - Longitudinal principal components analysis of patterns and predictors of growth
in Guatemalan children.
AB - Longitudinal principal components (LPC) analysis was used to assess growth
patterns in children from rural Guatemala in order to determine if this
methodology could provide additional information regarding correlates of growth
compared to more traditionally used methods based on attained size and
increments. LPC analysis reduces measures at many points in time into a few
parameters. However, LPC analysis requires complete data, and many cases may be
lost due to missing values. Thus the potentially greater sensitivity of LPC
analysis should be weighed against the reduced power resulting from smaller
sample sizes. Component indices representing centile level and centile shift,
attained size, and 3 to 36 month increments of growth in length and weight were
used as the dependent variables in multiple regression models in order to examine
the effects of environmental variables, such as home dietary intake,
supplementation, and prevalence of diarrhea on growth. Regardless of which growth
index, i.e., attained size, incremental change, or principal component, was used,
regression results were similar; higher nutritional intakes were generally
associated with greater and more rapid growth from birth to age 3 years. The
possible advantages of LPC analysis over more traditional methods were not great;
therefore, LPC analysis is not recommended as the method of choice in this
population.
PMID- 28520245
TI - Skin reflectance of children and young adults of Aymara ancestry.
AB - The skin reflectance of 556 Andean Indians of Aymara ancestry (305 males, 251
females; 10.0-29.9 yr) residing in La Paz, Bolivia (average altitude of about
3,600 m) is described. Reflectances were measured at three wavelengths (425 nm,
545 nm, and 685 nm) on two different sites, the medial surface of the upper arm
and forehead. Males tended to be significantly darker than females on both the
upper arm and forehead (P < .05). Female Aymara tended to lighten significantly
in skin color with age on both the upper arm and forehead, while males tended to
lighten significantly with age only on the upper arm (P < .05). The results of
comparisons between three categories based on paternal and maternal surnames (two
Aymara surnames, one Aymara and one Spanish surname, and two Spanish surnames)
were consistent with the hypothesis that the possession of Spanish surnames is
positively related to the degree of European admixture in urban Aymara. However,
the extent of admixture within each surname category may differ between rural and
urban Aymara, making classification by surnames problematic for rural-urban
comparisons.
PMID- 28520246
TI - Breif Reviews.
PMID- 28520247
TI - Skin and subcutaneous adipose tissue weights in older Japanese determined by
cadaver dissection.
AB - Forty-six embalmed cadavers of elderly Japanese 48 to 95 years of age, 35 males
and 10 females, were completely dissected, and the weights of skin and
subcutaneous adipose tissue were determined. Absolute and relative skin weight in
males (2.68 kg, 5.7%) were similar to those in females (2.73 kg, 6.1%). However,
females had more dissectible subcutaneous adipose tissue (5.82 kg, 12.3%) than
males (3.18 kg, 6.3%). These figures are comparable to dissection data obtained
from embalmed cadavers in Belgium which covered a similar age range. There were
statistically significant differences between Japanese and Belgians for body
weight and skin weight. However, there was no difference in relative skin weight.
Similar sex differences were apparent in the Japanese and Belgians. Skin and
subcutaneous adipose tissue weights were significantly correlated with body
weight in both sexes. Prediction equations for skin weight (SW) and subcutaneous
adipose tissue weight (SATW) from body weight in Japanese are SW (g) = 0.04357
Body weight + 638.3 (r = 0.70; SEE = 386.7 g) (for males and females); SATW (g) =
0.18902 Body weight - 5837.4 (r = 0.78; SEE = 1,328.3 g) (for males); and SATW
(g) = 0.36497 Body weight - 10581.5 (r = 0.79; SEE = 2,560.1 g) (for females).
PMID- 28520248
TI - Genetics, ethnohistory, and linguistics of Brac, Yugoslavia.
AB - Serogenetic data involving 21 genetic systems were collected from 12 villages on
the island of Brac (Yugoslavia) in 1987. Maximum sample size was 709 individuals.
The UPGMA dendrogram based on genetic distances was readily interpretable within
the contexts of village settlement history, social relationships, and sample size
considerations. The gene diversity value (H = 0.3029 +/- 0.0119) was both quite
high and extremely similar to the average heterozygosity value on the neighboring
Peljesac peninsula. Quadratic assignment procedures were used to investigate
genetic-linguistic-geographic correspondences. Unlike the Peljesac peninsula,
where the distance matrix correlations between genetics and linguistics, genetics
and geography, and linguistics and geography were all positive and highly
statistically significant; on Brac, only the linguistics-geography correlation
achieved statistical significance. Reasons for the differences are sought in the
different migrational characteristics of these two population systems, in the
complex interaction between evolutionary forces promoting population
differentiation (genetic drift) and homogeneity (gene flow), and in known
patterns of sociocultural interaction that might have skewed the genetic
geographic associations on Brac.
PMID- 28520249
TI - Validity of skinfold and girth based regression equations for the prediction of
body composition in obese adults.
AB - The validity of generalized and obese population-specific body composition
prediction equations for estimating percent fat was examined. Thirty-eight
clinically obese women (mean +/- SD, % fat = 46.4 +/- 5.2%, body mass = 97.2 +/-
17.7 kg, age = 41.8 +/- 13.3 years) and 16 clinically obese men (% fat = 39.2 +/-
3.8%, body mass = 126.7 +/- 24.6 kg, age = 43.0 +/- 11.6 years) had % body fat
estimated by hydrostatic weighing (with RV measured) and had a series of skinfold
and girth-based prediction equations applied to estimate % fat. The equations
were chosen because they were said to be "generalized" or because they were
"population specific" to obese samples of subjects. Results of the present study
indicated that the majority of prediction equations were not valid estimators of
% body fat in obese males and females. Of the equations that were valid
estimators of % body fat (mean differences in % fat of < 3%, r >= 0.70, SE < 5%),
all but one (Lohman, 1981) utilized girths as part of the prediction technique.
It was concluded that generalized girth-based equations could be utilized for
prediction of % body fat in obese subjects.
PMID- 28520250
TI - The relationship of body fat distribution to non-insulin-dependent diabetes
mellitus in a Navajo community.
AB - The relationship between non-insulin-dependent diabetes mellitus (NIDDM) and body
fat distribution (BFD) as measured by waist/hip circumference (WHR) was
investigated in a Navajo community. A sample of 136 females and 89 males, 20
years and older, was recruited using a cluster-sampling design. Fifty percent of
the females and 30.3% of the males are overweight [body mass index (BMI)
equivalent of >120% ideal body weight]. Prevalence of NIDDM is 14% in females and
10.1% in males. The sample is characterized by central BFD (mean WHR=0.897+/
0.075, females and mean WHR=0.963+/-0.071, males). WHR is significantly related
to age and BMI in males (P < 0.05), but not in females. Adjusted odds ratios for
risk of NIDDM prevalence with increasing WHR category were estimated from a
multiple logistic regression model which controlled for age and BMI. The odds
ratio and 95% confidence interval (95% CI) is 2.19 (1.14, 4.19) for risk of NIDDM
prevalence for a female in the middle BFD category compared to a female in the
low BFD category. Risk increases to 3.63 (95% CI=1.25, 10.52) for a female in the
highest BFD category. Although there is an increased risk of NIDDM prevalence
with central BFD for males, it is not statistically significant. Preferential
energy storage in abdominal fat depots may be a phenotypic expression of the
"Thrifty Genotype," which places American Indians at greater risk for metabolic
disorders.
PMID- 28520252
TI - Children's memories for events relating to treatment for eye cancer: Influence of
age at loss of eye.
AB - Treatment for retinoblastoma frequently involves removal of at least one eye in
the first 5 years. Variation in age of treatment leads to the assumption that
children's later verbal accessibility of early traumatic memories may vary, with
some children having less opportunity to make sense of their condition. Video
recordings were made of 17 children who had undergone enucleation either before
24 months (n = 8) or after 24 months (n = 9) involved in "hospital play'' using
props designed to elicit talk about "eyes." The hypothesis that a larger number
of verbalizations about medical procedures would occur in children enucleated
after 24 months than before 24 months was supported. Children enucleated after 24
months engaged in significantly more talk about enucleation and/or examination
under anesthetic whereas none of the children enucleated in infancy talked about
these medical events. The outcome supports the view that there is a transition
around 24 months in the extent to which children can have verbal access to
previous traumatic memories. The design of interventions needs to take into
account that children enucleated in infancy have less opportunity for later
verbal access to early memories of traumatic events than those treated later,
leading to possible misconceptions about their own condition.
PMID- 28520253
TI - Infants placed in foster care prior to their first birthday: Differences in kin
and nonkin placements.
AB - Using data from the National Survey of Child and Adolescent Well-Being, this
study examines differences between kinship and foster placements for infants
placed in out-of-home care prior to their first birthday. The differences
examined include developmental status at time of placement, differences in the
home and neighborhood environments, and the duration of time in placement.
Participants included 457 infants placed in either kinship or foster care and
their caregivers. Findings suggest that infants placed with kin had fewer
developmental concerns 2 to 6 months after the initial Child Protective Services
investigation and spent significantly less time in placement. The quality of
foster and kinship homes and neighborhoods also differed: Foster homes were
generally of better quality and located in safer neighborhoods. Overall, for both
kin and foster care, the data suggest that even after passage of the Adoption and
Safe Families Act of 1997 (ASFA, Public Law 105-89), infants remain in care for a
long time: Approximately one third of infants are still in out-of-home care 3
years after the initial investigation.
PMID- 28520251
TI - Interactive coordination of currently depressed inpatient mothers and their
infants during the postpartum period.
AB - In healthy mother-infant dyads, interactions are characterized by a pattern of
matching and mismatching interactive states with quick reparation of mismatches
into matches. In contrast, dyads in which mothers have postpartum depression show
impaired mother-infant interaction patterns over the first few months of the
infant's life. The majority of studies that have examined such interaction
patterns have drawn on community samples rather than on depressed inpatient
samples of mothers who were in a state of current depression at the time of
assessment. To date, no study has investigated specific microanalytic patterns of
interactive coordination between depressed German mothers and their infants using
the Face-to-Face Still-Face paradigm (FFSF). The primary goal of this study was
to evaluate specific patterns of dyadic coordination and the capacity for
repairing states of miscoordination in an inpatient sample of postpartum
currently depressed mothers and their infants as compared with a healthy control
group. A sample of 28 depressed inpatient German mothers and their infants (age
range = 1-8 months, M age = 4.06 months) and 34 healthy dyads (range = 1-8
months, M age = 3.89 months) were videotaped while engaging in the FFSF. A focus
was placed on the play and reunion episodes. Compared with healthy dyads, dyads
with depressed mothers showed less coordination of positive matched states and
longer latencies when repairing interactive mismatching states into positive
matched states. Clinical implications are discussed.
PMID- 28520254
TI - The psychology of infant colic: A review of current research.
AB - Colic, or excessive infant crying, occurs during the first 3 months in
approximately 15 to 20% of infants and is the most common concern for which
parents seek medical advice during an infant's first year. Various physiological
and environmental causes have been investigated. Some researchers have proposed
multifactorial causes while others have argued that it is simply the extreme end
of the normal crying continuum. As the etiology of colic is not clear,
definitions of colic have relied on behavioral descriptions, and the relative
merits of specific behaviors in affording an accurate definition are debated.
This lack of clarity has compounded difficulties in identifying effective
interventions for colic. One point of agreement is that colic is extremely
distressing for parents. Some have argued that the disruption to the infant
parent relationship can have long-term implications for development while others
have argued that only if the crying persists beyond 3 months is there a risk of
long-term implications. It is concluded that due to the incidence of colic and
the immediate impact it has on family functioning, more research is required to
further our understanding of colic. In addition, the identification of effective
coping strategies and consoling methods to assist parents through this stressful
period is required.
PMID- 28520256
TI - Stresses of conquest: A study of Wilson bands and enamel hypoplasias in the Maya
of Lamanai, Belize.
AB - This paper examines the prevalence of Wilson bands and hypoplasias in the dental
enamel of a sample of Postclassic and Historic Maya Indian remains from the
archaeological site of Lamanai, Belize. Mandibular canines were removed from 23
individuals from the two periods. The surface of a polished, acid etched,
longitudinal section of each canine was examined with scanning electron
microscopy for the presence of enamel malformations. A large number of Wilson
bands and shallow hypoplasias were identified; however, more severe macroscopic
hypoplasias were rare. The two kinds of defects were found to be temporally
associated in only 25-50% of instances, indicating that circumstances leading to
their formation are likely distinct. The mean number of both Wilson bands and
shallow hypoplasias was found to be significantly different between samples,
indicating an increase in developmental stress in the Historic occupation. As
dietary differences have not been detected between the occupations, the observed
differences in enamel defect prevalence can be attributed to the effects of
changing epidemiological patterns following the Spanish conquest.
PMID- 28520257
TI - Commingling analysis of blood pressure in the Tecumseh community health study.
AB - A commingling analysis of the distribution of systolic and diastolic blood
pressure was performed on measurements from 9,226 individuals living in Tecumseh,
Michigan during 1962-1965. Even after correcting for skewness in the
distributions, multiple normal distributions fit the data significantly better
than a single normal one, suggesting some level of commingling. The exact nature
of the components differed depending on the phenotype, and the number of
components entertained, suggesting a possibly complex etiology, but with some
definite qualitative effects. Segregation analysis under the mixed model is
needed to address the nature of blood pressure in this community more
definitively.
PMID- 28520255
TI - Core-Shell and Layer-by-Layer Assembly of 3D DNA Crystals.
AB - A long-standing goal of DNA nanotechnology has been to assemble 3D crystals to be
used as molecular scaffolds. The DNA 13-mer, BET66, self-assembles via Crick
Watson and noncanonical base pairs to form crystals. The crystals contain solvent
channels that run through them in multiple directions, allowing them to
accommodate tethered guest molecules. Here, the first example of
biomacromolecular core-shell crystal growth is described, by showing that these
crystals can be assembled with two or more discrete layers. This approach leads
to structurally identical layers on the DNA level, but with each layer
differentiated based on the presence or absence of conjugated guest molecules.
The crystal solvent channels also allow layer-specific postcrystallization
covalent attachment of guest molecules. Through controlling the guest-molecule
identity, concentration, and layer thickness, this study opens up a new method
for using DNA to create multifunctional periodic biomaterials with tunable
optical, chemical, and physical properties.
PMID- 28520258
TI - Genetic studies of human apolipoproteins: XII. Population genetics of
apolipoproteins in Papua New Guinea.
AB - The gene products of the apolipoprotein A-I, A-II, A-IV, C-II, C-III, D, E and H
loci have been screened by isoelectric focusing followed by immunoblotting from
two Papua New Guinean populations, the Huli and the Pawaia. Only APO E and APO H
revealed common polymorphisms. A putative unique A-IV variant has been
identified, but due to the lack of family data it is not characterized further.
Three common APO H alleles were observed in both groups with comparable
frequencies. But significantly different distributions of three APO E alleles
were noted in the Huli and the Pawaia. The respective frequencies of the APO E*2,
APO E*3, and APO E*4 alleles were 0.154, 0.356, and 0.490 in the Huli and 0.138,
0.603, and 0.259 in the Pawaia. A strikingly high frequency of the APO E*4 allele
in Papua New Guinea may provide a useful insight into the studies of genetic and
environmental interactions in controlling the cholesterol levels in the general
population.
PMID- 28520259
TI - Asymmetry and intraindividual diversity in digital dermatoglyphics of Bulgarians.
AB - A random sample of 2,130 apparently healthy Bulgarians, 1,065 of each sex, was
investigated to obtain a detailed picture of finger dermatoglyphic asymmetry and
intraindividual diversity in the population examined. Both sexes showed an almost
equal pattern of asymmetry and diversity. Relative pattern asymmetry, taking into
account the pattern type frequencies, tends to be higher in males, being
especially pronounced on fingers which show a low asymmetry in other aspects.
Like other populations so far examined, Bulgarians display higher rates in males
than in females concerning the total, ulnar, and radial ridge-counts, their
asymmetries, and intraindividual diversities. However, the more analysis of the
ridge-count asymmetry is worked out in detail, the more it becomes evident that
both sexes are asymmetrical not so much to a different degree as in a different
manner. As a whole, the ambidirectional, directional, fluctuating, and relative
asymmetries are practically consistent in both sexes. Important sex differences
are revealed in the structure of the directional and fluctuating asymmetries
concerning contrasts between their radial and ulnar levels. The sex differences
in directional asymmetry are discussed in the light of possible effects of the
sex chromosomes upon the mediolateral developmental gradients. Expressed
modulation of the fluctuating asymmetry by finger is interpreted as evidence for
considerable differences between separate finger pairs in their sensitivity to
stressful factors. Presented results are relevant to anthropology and population
genetics and could have implications in medical genetics and teratology, serving
as normative data in pathological conditions.
PMID- 28520261
TI - Search for secular trends in calvarial diameters, cranial base height, indices,
and capacity in South African Negro crania.
AB - Two hundred eighteen South African Negro male crania were arranged in 5-year
birthdate cohorts from 1880-1884, 1890-1894, up to 1930-1934 inclusive and
investigated for the presence of a secular trend in their dimensions. Maximum
breadth, maximum length, basibregmatic height, cranial base height, and bi
auricular breadth (BAB) were measured, and cranial index (CI), cranial capacity
(CC), and cranial base height index (CBHI) were determined. Cranial length
exhibited a significant increase from 1890 to 1930. Cranial base height and CBHI
exhibited statistically significant declines over the same period. The absence of
secular trends in the other dimensions studied corresponds to previous analyses
of the lengths of the femora and tibiae of the same sample. The secular trends in
cranial length, cranial base height and its index, and the absence of trends in
the other dimensions, are discussed in relation to an apparent decrease in the
standard of living occurring in this population after 1900. It is unlikely that
the absence of a positive secular trend denotes the attainment of a genetically
determined ceiling to the physical size of the subjects represented by these
skeletons. It is more likely that the environmental factors believed to produce a
positive secular trend were absent in the years from which this sample was drawn
and that signs of improvement in these factors, if any, would be so recent that
evidence of their effect is not yet available from our cadaver-derived skeletons.
PMID- 28520260
TI - Selective neutrality of surname, distribution in an immigrant indian community of
Houston, Texas.
AB - From survey data on surnames in an immigrant community of Indians in Houston,
Texas, it is shown that the family size distribution and the distribution of the
number of male children per family are independent of the surnames of the
parents. This provides a direct test of selective neutrality of surname
distributions. A genetic theory of sampling distribution of neutral alleles is
employed to estimate the parameter of the surname distribution, and analytical
results for the expectation and variance of the frequencies of surnames with a
different number of copies in a sample are provided. It is also shown that the
surname distribution may indicate presence of mixture in a sample, which can be
examined by such theoretical approaches. The transition of surname distributions
in two successive generations is shown to follow the pattern predicted by random
extinction of surnames.
PMID- 28520262
TI - Variation in body size and shape among South American Indians.
AB - Available information on mean adult male and female height, weight, sitting
height, and relative sitting height for 62 groups is used to examine the
relationship between anthropometric measurements and climate, geographical
location, and linguistic affiliation among South American Indians. Results of
correlation analysis indicate that height increases from the north to the south
of the continent and is significantly negatively correlated with precipitation
but is not significantly correlated with most measures of temperature. Only in
females is weight significantly correlated with any of the location or climatic
variables. Sitting height is correlated with both temperature and precipitation,
while relative sitting height is more strongly correlated with temperature, and
the direction of the correlation indicates that groups living in colder areas
have relatively shorter legs. The interpretation of the correlations for sitting
height and relative sitting height is complicated by the fact that the
correlations of these measurements change when only the low-altitude groups in
the data set are considered. There are no significant differences in male height
between linguistic stocks when the analysis is limited to those stocks
represented by at least five groups. In general, there appears to be more
patterning in body size and shape variation in South America than there is in
terms of genetic variation. The correlations between anthropometric measurements
and climate in South America differ in some ways from those observed for other
areas of the world.
PMID- 28520263
TI - Reduction in birth weight associated with smoking among young and older-age
women.
AB - This study examined the combined effects of maternal smoking and maternal age on
birth weight. A sample of 1,851 white, full-term infants (37 to 42 weeks) born to
primiparous mothers ranging in age from 18 to 41 years was derived from the
database of the Child Health and Development Studies (CHDS), available through
the National Technical Information Service (NTIS) of the U.S. Department of
Commerce. The mothers were classified into three age groups-young, middle-aged,
and older-aged-corresponding respectively to values below the 15th, between the
15th and 85th, and at or above the 85th percentile of age. Analyses of the data
show that the reduction in birth weight associated with maternal smoking when
compared with nonsmoking averaged 181 gm for the young group (18 to 20 years),
162 gm for the middle-aged group (21 to 29 years), and 154 gm for the older-aged
group (30 to 41 years). These differences are independent of total income. Hence
it appears that the birth weight-reducing effect of smoking is not enhanced among
women of older reproductive ages (30 to 41 years). Furthermore, the reduction in
birth weight is dose responsive. That is, the greater the number of cigarettes
smoked per day, the lower is the resulting mean birth weight and the higher is
the proportion of low-birth-weight infants.
PMID- 28520264
TI - War trauma lingers on: Associations between maternal posttraumatic stress
disorder, parent-child interaction, and child development.
AB - Maternal traumatization has been proposed as a risk factor for child development,
but the mechanisms involved are poorly understood. This study analyzed the
interrelations among maternal posttraumatic stress symptoms, parent-child
interaction (emotional availability), and infants' psychosocial functioning and
development among 49 asylum-seeker and refugee mothers and their children (18-42
months). Measures included assessment of mothers' trauma and comorbid symptoms
(Harvard Trauma Questionnaire: R.F. Mollica et al., 1992; Hopkins Symptom
Checklist: L. Derogatis, R. Lipman, K. Rickels, E. Uhlenhuth, & L. Covi, 1974),
emotional availability within parent-child interaction (Emotional Availability
Scales: Z. Biringen, 2008), and infants' psychosocial functioning (Child Behavior
Checklist: T.M. Achenbach & L.A. Rescorla, 2000) and development (Bayley Scales
of Infant Development: B.F. van der Meulen, S.A.J. Ruiter, H.C. Spelberg, & M.
Smrkovsky, 2000). The results show that higher levels of maternal posttraumatic
stress symptoms are associated with a higher level of psychosocial problems of
infants, but not with delays in their mental or psychomotor development. The
results also show that higher levels of maternal posttraumatic stress symptoms
are associated with higher levels of insensitive, unstructuring, or hostile, but
not intrusive, parent-child interactions. Infants show lower levels of
responsiveness and involvement to their traumatized mothers. Parent-child
interaction did not function as a mediator between maternal trauma symptoms and
infants' psychosocial functioning. Results are discussed in relation to the
dyad's regulation of emotions. Results implicate a need to reestablish attunement
between traumatized mothers and their nontraumatized children.
PMID- 28520265
TI - Biological and physiological markers of tactile sensorial processing in healthy
newborns.
AB - The main objective of this review is to provide a descriptive analysis of the
biological and physiological markers of tactile sensorial processing in healthy,
full-term newborns. Research articles were selected according to the following
study design criteria: (a) tactile stimulation for touch sense as an independent
variable; (b) having at least one biological or physiological variable as a
dependent variable; and (c) the group of participants were characterized as full
term and healthy newborns; a mixed group of full-term newborns and preterm
newborns; or premature newborns with appropriate-weight-for-gestational age and
without clinical differences or considered to have a normal, healthy
somatosensory system. Studies were then grouped according to the dependent
variable type, and only those that met the aforementioned three major criteria
were described. Cortisol level, growth measures, and urinary catecholamine,
serotonin, and melatonin levels were reported as biological-marker candidates for
tactile sensorial processing. Heart rate, body temperature, skin-conductance
activity, and vagal reactivity were described as neurovegetative-marker
candidates. Somatosensory evoked potentials, somatosensory evoked magnetic
fields, and functional neuroimaging data also were included.
PMID- 28520266
TI - Maternal attachment representations and the development of very low birth weight
premature infants at two years of age.
AB - There is a consensus that prematurity could increase the risk of attachment
impairment. We studied 90 premature children with very low birth weights (<1,500
g) and 96 healthy children born at term with similar age and sociodemographic
characteristics. Our objective was to assess maternal stress and attachment
representations, and compare development indices on both groups at 2 years of
age. Premature infants had a medium-to-severe degree of immaturity and biological
risk (M gestational age = 29.98 weeks; birth weight = 1,159.76 g), with 57%
staying in the ICU >=1 week. These children born prematurely had lower scores on
the development indices within the normal range. Mothers of premature infants (n
= 74) reported higher levels of stress during their first year of life (59%) than
did controls (41%), but no significant differences were detected in maternal
attachment discourse between the two groups. The findings confirm that premature
birth has a great influence on maternal emotional responses and the health and
development of children in the first years of life, and indicate that stress
responses in parents and warning signs for attachment problems should be assessed
as early as possible.
PMID- 28520267
TI - Parental involvement in home visiting: Interpersonal predictors and correlates.
AB - Parents' commitment to and usage of early intervention are key variables in
understanding discrepancies in families' susceptibility to these services.
Although the important role of fathers in infant development is widely
recognized, early interpersonal predictors of paternal involvement in home
visiting programs have been understudied. This article aims to fill this gap by
regressing parents' postnatal involvement on prenatal partnership satisfaction
and quality of the helping relationship in a sample of 124 socially and
financially disadvantaged families. Paternal program engagement was predicted by
partnership satisfaction whereas the perceived quality of the helping
relationship best predicted maternal program engagement, with demographical
characteristics controlled. Maternal program engagement also mediated the
relationship between partnership satisfaction and paternal program engagement.
The results are discussed against the theoretical background.
PMID- 28520268
TI - Colic: What's maternal mental health got to do with it?
AB - Families can benefit when pediatric and mental health professionals have a
greater appreciation of psychological and relational issues that arise in the
course of caring for an infant with colic. The Infant Behavior, Cry, and Sleep
Clinic is a multidisciplinary, clinical intervention for parents who identify
infant crying as adversely affecting infant, parental, and/or family functioning.
Pairing pediatric and mental health expertise provides parents with strategies to
manage infant colic within a context that recognizes parental mental health
needs. Clinical case material illustrates varying responses and degrees of
psychological distress in mothers whose infants have colic. Treatment approaches
to colic that take into account maternal mental health needs may contribute to
more optimal infant, maternal, and family outcomes.
PMID- 28520269
TI - Mothers' affect dysregulation, depressive symptoms, and emotional availability
during mother-infant interaction.
AB - Maternal affect dysregulation and maternal depressive symptoms were examined as
predictors of maternal emotional availability (EA) during mother-infant
interaction in a nonclinical sample. In particular, we investigated if affect
dysregulation predicts EA and is more important than are depressive symptoms in
predicting EA. Questionnaire measures and 30 min of free play were obtained from
46 mothers of 4- to 5-month-old infants. Mothers' self-reported affect
dysregulation was inversely related to EA, but mothers' depressive symptoms were
not related to EA. More specifically, mothers' tendency to use unhealthy
externalizing behaviors to reduce tension and distress predicted less EA. These
results suggested that even in relatively low-risk samples, mothers' self
reported affect dysregulation, particularly the tendency to act out
inappropriately in response to tension and distress, may be a more proximal
predictor of EA than are depressive symptoms.
PMID- 28520270
TI - Psychotherapy groups and individual support to enhance mental health and early
dyadic interaction among drug-abusing mothers.
AB - The purpose of this controlled study was to examine the outcome of psychodynamic
mother-infant group psychotherapy (PGT) outpatient intervention for drug-abusing
perinatal mother-infant dyads. PGT comprised 20 to 24 weekly 3-hr sessions with 3
to 5 months of follow-up. A comparison intervention group was formed of mothers
participating in individually tailored psychosocial support (PSS) lasting, on
average, 12 months and providing mother-infant support and practical counseling.
We hypothesized that positive changes would occur in maternal drug abuse, mental
health, and mother-infant interaction, especially in the PGT group due to its
more intensive therapeutic focus. Participants were 26 drug-abusing dyads in PGT,
25 in PSS, and 50 dyads in a non-drug-abusing comparison group. Assessments were
pre-intervention and at 4 and 12 months' follow-up, including maternal depressive
symptoms and mother-child interaction assessed by the Emotional Availability
Scales (EA). As hypothesized, in dyadic interaction maternal hostility decreased
significantly in the PGT group, and intrusiveness decreased in both intervention
groups, but especially in the PTG group. However, both interventions showed a
general improvement in the quality of mother-infant interaction. They also
succeeded in sustaining high maternal abstinence, treatment retention, and
alleviating depressive symptoms. The findings are discussed in relation to
preventing negative transgenerational interaction patterns in the high-risk
dyads.
PMID- 28520271
TI - Development and initial validation of an outcome measure for home visitation: The
healthy families parenting inventory.
AB - The Healthy Families Parenting Inventory (HFPI) is a 63-item outcome measure that
was designed to examine change in nine parenting-related domains. The HFPI was
developed to respond to the need for an outcome measure for home visitation
programs that is relevant to the intervention, sensitive to change, and
appropriate with a diverse participant base, and would produce data that are
immediately useful in practice. The authors detail the steps in the development
and initial validation of the HFPI. The pattern of inter-item and item-to
subscale correlations as well as an exploratory factor analysis and sensitivity
to change analysis support the nine-factor model of the HFPI.
PMID- 28520272
TI - A focus on polarity: Investigating the role of orientation cues in mediating
student performance on mRNA synthesis tasks in an introductory cell and molecular
biology course.
AB - The central dogma has served as a foundational model for information flow,
exchange, and storage in the biological sciences for several decades. Despite its
continued importance, however, recent research suggests that novices in the
domain possess several misconceptions regarding the aforementioned processes,
including those pertaining specifically to the formation of messenger ribonucleic
acid (mRNA) transcripts. In the present study, we sought to expand upon these
observations through exploration of the influence of orientation cues on
students' aptitude at synthesizing mRNAs from provided deoxyribonucleic acid
(DNA) template strands. Data indicated that participants (n = 45) were proficient
at solving tasks of this nature when the DNA template strand and the mRNA
molecule were represented in an antiparallel orientation. In contrast,
participants' performance decreased significantly on items in which the mRNA was
depicted in a parallel orientation relative to the DNA template strand.
Furthermore, participants' Grade Point Average, self-reported confidence in
understanding the transcriptional process, and spatial ability were found to
mediate their performance on the mRNA synthesis tasks. Collectively, these data
reaffirm the need for future research and pedagogical interventions designed to
enhance students' comprehension of the central dogma in a manner that makes
transparent its relevance to real-world scientific phenomena. (c) 2017 by The
International Union of Biochemistry and Molecular Biology, 45(6):501-508, 2017.
PMID- 28520273
TI - Efficacy of a Targeted Drug Delivery on-Demand Bolus Option for Chronic Pain.
AB - BACKGROUND AND OBJECTIVES: Intrathecal targeted drug delivery systems
historically required physician office visits for dose adjustment to manage
fluctuating pain. A wireless device now enables patients to supplement their
basal intrathecal infusion with a programmed on-demand bolus dose. We sought to
quantify the change in oral breakthrough opioid need associated with the use of
an intrathecal bolus in comparison to those treated with the basal infusion
alone. METHODS: Demographic, dosage, bolus usage and longevity data were
extracted from the historical medical record of 69 patients (18/51
bolus/nonbolus) followed continuously at our center. Medication consumption and
Pain Disability Index measures were obtained at baseline and most recent follow
up. RESULTS: Among patients with the bolus option, only 2 (11%; confidence
interval [CI] 0% to 26%) continued to require oral opiates to manage breakthrough
pain compared to 29 (57%; CI 43% to 71%) without the bolus option. The Pain
Disability Index score decreased by 19% in patients with the bolus option and by
25% in those with the basal infusion. Total daily intrathecal opioid intake was
34% lower in the group with the bolus device. CONCLUSIONS: Utilizing an
intrathecal bolus to treat incident pain was a safe way to manage unpredictable
breakthrough pain and may represent a cost-saving opportunity by eliminating the
need for oral analgesic medications.
PMID- 28520274
TI - Influence of behavioral concerns and early childhood expulsions on the
development of early childhood mental health consultation in Colorado.
AB - This article examines how the Colorado study Children With Social, Emotional and
Behavioral Concerns and the Providers Who Support Them (S.D. Hoover, 2006) was
used to advance a statewide agenda for early childhood mental health consultation
in Colorado. The study involved a survey of licensed childcare providers
throughout the state asking about the behavior of children in their care and
their responses to that behavior. Exclusion of children from early care and
education settings due to challenging behavior was found to be a significant
problem taking a toll on families, children, and early care and education
providers. Importantly, results from the survey indicated that the rate of
exclusion of children from care due to challenging behavior was lower for family
childcare providers who had access to mental health consultation. Recommendations
are offered regarding the infrastructure needed to sustain mental health
consultation capacity in early care and education settings, and related policies
and practices.
PMID- 28520275
TI - Forgotten survivors of intimate-partner violence: The role of gender and
mothering in infant development.
AB - Although gender and mothering are critical factors in the development of infants
exposed to intimate-partner violence (IPV), the majority of research has focused
on school-age and adolescent populations. The aim of this study was to
investigate the moderating effect of gender in the relationship between mother
infant interaction and infant development in families of IPV. Maternal report was
used to measure infants' cognitive and social functioning while mother-infant
interaction quality was assessed through an observational measure. Participants
consisted of 44 mothers and their infants (4-43 months of age). While male
infants showed poorer fine motor, problem-solving, and personal-social skills
than did their female counterparts, comparable gross motor and communication
skills were demonstrated. Moderator analysis for gender indicated that the
association among maternal cognitive growth fostering and gross motor skills was
significantly stronger for boys than it was for girls. No other moderator effects
were detected. Analysis examining age, gender by age, and infant competencies did
not reveal significant effects. Implications for clinical practice are
considered, with special attention paid to women as mothers.
PMID- 28520276
TI - Expanding early childhood mental health consultation to new venues: Serving
infants and young children in domestic violence and homeless shelters.
AB - The number of infants and young children affected by homelessness and domestic
violence is growing, and the effect of these experiences on children is wide
ranging. Early childhood mental health consultation (ECMHC) has expanded to these
settings to help the adults attend to very young children whose needs are often
obscured by families' crises. Recent research in ECMHC to childcare has cited the
salience of the consultant-consultee relationship as the central contributor to
positive change in caregiver's behavior and children's experience. This article
explores the similarities and variations in the consultant's way of being that
are necessary to expand this relationship-based ECMHC model to adult-focused
settings. This has incorporated a combination of consultative shifts: expanded
training, appreciation for families' survival priorities, attention to the
effects of unavoidable adult decisions on children, increased tolerance for the
affect this raises in parents and caseworkers, and greater efforts to create
space for reflection and thinking. Caseworkers' attenuated contact with and
limited prior knowledge about young children creates challenges in identifying
and responding to concerns about children. The particular systemic and relational
difficulties that emerge in shelters and that influence caseworkers'
responsiveness to clients are explored.
PMID- 28520277
TI - A multilevel analysis of consultant attributes that contribute to effective
mental health consultation services.
AB - A positive relationship between the mental health consultant (MHC) and early care
and education staff is considered important for achieving positive early
childhood mental health consultation outcomes, but little is known about the
attributes of MHCs that contribute to relationships with staff and to staff
reported child outcomes. This study was a secondary analysis of 57 MHCs and 407
Head Start staff who responded to the Head Start Mental Health Services Survey.
Hierarchical linear models examined the relationship between five attributes of
MHCs and staff reports of improved child outcomes and a positive relationship
with the MHC. The results suggest that MHC reports of positive relationships with
staff, positive relationships with families, and high levels of supervision and
support are positively associated with staff reports of positive relationships
with the MHC (p < .05). None of the MHC-reported attributes were associated with
staff-reported child outcomes.
PMID- 28520278
TI - Assessing fidelity for early childhood mental health consultation: Lessons from
the field and next steps.
AB - Early childhood mental health consultation (ECMHC) has become a common approach
to delivering mental health services and supports for young children, their
families, and the early care and education community. While many states and
communities are implementing some form of ECMHC, the evidence base is still
developing. One obstacle to building a rigorous evidence base has been a lack of
focus on fidelity measurement, and one barrier to fidelity assessment has been a
lack of a common framework for the essential components of effective ECMHC. This
article briefly summarizes the development of a conceptual model for effective
ECMHC based on a qualitative study of six ECMHC programs with positive outcomes
(F. Duran et al., 2009). The common components and processes derived from those
six programs are then used to articulate an approach for operationalizing
fidelity. Specific examples of strategies used to support fidelity by three of
the six programs are highlighted. We close with a discussion of the implications
of these approaches and suggestions for next steps in defining a consensus-based
model for measuring fidelity to ECMHC services. Abstracts translated in Spanish,
French, German, and Japanese can be found on the abstract page of each article on
Wiley Online Library at http://wileyonlinelibrary.com/journal/imhj.
PMID- 28520279
TI - Therapeutic play within infant-parent psychotherapy and the treatment of infant
feeding disorders.
AB - This clinical article presents an infant mental health approach to the treatment
of feeding disorders in infants and toddlers that involves the infant-parent
psychotherapist directly working with the infant's representations within infant
parent psychotherapy sessions. The treatment is informed by an assessment of the
infant's emotional development, subjective experience, and the dynamics of the
infant-parent relationship. This model involves therapeutically using play and
words with infants and draws upon concepts from D.W. Winnicott and attachment
theory as well as principles from the psychodynamic treatment of posttraumatic
stress disorder in infants. The model was developed from clinical work over 2
decades in a tertiary pediatric hospital with infants who presented with feeding
disorders ranging from breast or bottle refusal, refusal to wean onto solids,
feeding aversion, tube dependency, and failure to thrive.
PMID- 28520280
TI - The consultation relationship-From transactional to transformative: Hypothesizing
about the nature of change.
AB - Increasing numbers of young children with significant social and emotional
difficulties are being identified in childcare settings. Early Childhood Mental
Health (ECMH) Consultation has been identified as a promising practice in
stemming the tide of this troublesome trajectory. While ECMH Consultation is
credited with promoting children's positive development, diminishing difficult
behaviors, and reducing expulsion rates, the mechanisms of this transformative
process are only beginning to be investigated. Recent research cites the salience
of the relationship between a consultant and consultee as the central contributor
to positive change in childcare-center climate and child outcomes. This article
delineates characteristics of a beneficial consultative relationship and
postulates the clinical process by which change in childcare providers' behavior
occurs as a result of having experienced such a relationship. Paralleling the
traits of contingent caregiving, the consultative stance, a posture of mutuality,
reciprocity, and positive regard creates an intersubjective space for reflection,
repair, and, when necessary, adaptation. Based on perceptual shifts or
expansions, the providers' attitude and approach toward children in their care is
amended, in turn promoting positive change in the child and classroom atmosphere.
PMID- 28520281
TI - Parental representations: A systematic review of the working model of the child
interview.
AB - This review provides an overview of results that have been obtained in studies
using the Working Model of the Child Interview (WMCI). The WMCI is a structured
interview that assesses parents' internal working models of the relationship with
their young children. From the current infant mental health perspective,
evaluating the quality of parents' representations about the infant-parent
relationship is the main focus in the assessment and treatment of infants and
their parents. Empirical quantitative studies (N = 24 articles) in which the WMCI
was used for data collection were used for analysis. The distribution of
balanced, disengaged, and distorted representations differed among various study
populations. Parents' internal representations as reflected in their narratives
about their child are affected by various factors such as maternal, child, and
demographic characteristics. The WMCI is a valid and useful clinical and research
tool that can be used in future studies examining the role of parental
representations in infant development.
PMID- 28520282
TI - Implementing a statewide early childhood mental health consultation approach to
preventing childcare expulsion.
AB - State- and local-level mental health administrators and practitioners can work
collaboratively to provide effective early childhood mental health consultation
(ECMHC) services that address the growing need in communities to promote healthy
socioemotional functioning in infants and young children and prevent longer term
mental health challenges. This article describes one state's model of ECMHC, the
Child Care Expulsion Prevention Program (CCEP), as well as preliminary evaluation
findings on consultants' fidelity to the developed approach to service within 31
counties in Michigan. The CCEP approach is flexible, yet adheres to six
cornerstones which are essential to effectively and consistently carrying out
services across local projects, including the provision of relationship-based
programmatic and child/family-centered consultation, hiring and supporting high
quality consultants through professional development and reflective supervision,
ongoing provision of state-level technical assistance, use of evidence-based
practices, and collaboration with other early childhood service providers. In
addition to the overview of CCEP's approach and effectiveness, lessons learned
are provided to guide those engaged in policy development, practice, and applied
research pertaining to ECMHC. Abstracts translated in Spanish, French, German,
and Japanese can be found on the abstract page of each article on Wiley Online
Library at http://wileyonlinelibrary.com/journal/imhj.
PMID- 28520283
TI - Building the evidence base for early childhood mental health consultation: Where
we've been, where we are, and where we are going.
PMID- 28520284
TI - Improved classroom quality and child behavior in an Arkansas early childhood
mental health consultation pilot project.
AB - The aim of the current study was to examine the effects of early childhood mental
health consultation (ECMHC) on teacher-level and child-level outcomes in the
context of a partnership between community mental health centers in three regions
of Arkansas and publically funded early education programs (14 intervention sites
and 4 comparison sites). From 2005 to 2008, 193 teachers participated in the
study, along with 1,448 children. Data-collection activities included structured
classroom observations, teacher ratings of children's strengths and behavior, and
teacher surveys to assess satisfaction with ECMHC services. Results suggest that
teachers were highly satisfied with the consultation services and that teachers
receiving the intervention had lower levels of permissiveness and detachment,
with a trend toward higher levels of sensitivity in interactions with children in
their classroom. In terms of child outcomes, we found that by the third year of
the project, children at intervention sites were rated by their teachers as
having fewer behavior problems and more protective factors.
PMID- 28520285
TI - Effect of moderate weight loss on ovarian function assessed by salivary
progesterone measurements.
AB - The effects of moderate, voluntary weight loss on ovarian function are studied by
monitoring the daily levels of salivary progesterone in 8 dieting women (18
cycles) and 9 age-matched controls (19 cycles). Both groups of women were within
normal standards of weight for height, though the dieters were significantly
heavier than the controls. Dieters lost weight at an average rate of 1.9 +/- 0.3
kg/mo during the study. Dieters' cycles during periods of weight loss (weight
loss cycles) have significantly lower peak levels of luteal progesterone
(controls 655 +/- 46 pmol/L, weight loss 461 +/- 67 pmol/L; P < 0.005) and lower
average levels of luteal progesterone (controls 287 +/- 30 pmol/L, weight loss
214 +/- 23 pmol/L; P < 0.005) than do controls. All control cycles were
classified as ovulatory by virtue of at least one salivary progesterone reading
>= 300 pmol/L. Only 62% of the weight loss cycles were classified as ovulatory by
this criterion. Where longitudinal weight data are available both the magnitude
and duration of progesterone elevation correlates significantly with net weight
change during the preceding cycle and show no significant correlation with net
weight change during the current cycle. Examination of individual profiles
confirms that the most profound suppression of luteal activity usually occurs
during post-loss rather than weight loss cycles, even if weight is stable or
increasing during the post-loss cycle itself. These results, together with field
studies of African horticultural populations, suggest that human ovarian function
may be adapted to modulate waiting time to conception in response to trends in
energetic balance.
PMID- 28520286
TI - Reciprocal causal influences among malnutrition, growth retardation, and diarrhea
in preschool children.
AB - Structural regression models are applied to longitudinal data to study reciprocal
causal influences between malnutrition and infection in preschool children. Two
models of three waves (time periods) are applied: a two-variable model, the
variables being acute malnutrition and diarrhea; and a three-variable model,
which includes chronic malnutrition as a third variable. Malnutrition is measured
by standardized weight for age and standardized height for age, and enteric
infection is measured by diarrhea. The latter is expressed as the number of days
with diarrhea or fever divided by the number of days at risk in the trimester
preceding anthropometric assessment. The data used in the analysis were gathered
as part of a longitudinal study to estimate the effects of nutrition on mental
and physical growth, conducted by the Institute of Nutrition of Central America
and Panama (INCAP) in rural Guatemala. The sample comprises 508 children with
complete data from families residing in four rural villages. Results provide
evidence of significant causal influence of both diarrhea on acute malnutrition
and of acute malnutrition on diarrhea. A cumulative effect of acute malnutrition
on chronic malnutrition that leads to growth retardation is identified.
Accordingly, interventions aimed at decreasing the causal effect of infection on
malnutrition, as well as interventions aimed at improving the nutritional
condition of children, are required.
PMID- 28520287
TI - Longitudinal growth of high socioeconomic status Guatemalan children analyzed by
the Preece-Baines function: An international comparison.
AB - The Preece-Baines model I function, adapted for use with a personal computer, is
applied to the longitudinal growth records of Guatemalan children and adolescents
of high socioeconomic status. The fit of the Preece-Baines function to the
Guatemalan data is compared with those of published analyses of the function
fitted to the growth of British, Belgian, urban and rural Indian, Australian
Aborigine, and African children. Guatemalan, British, and Belgian samples share
generally favorable environments for human development and show few differences
in the amount and velocity of growth, or in the timing of growth events. Urban
Indians live under relatively good environmental conditions and are similar to
Guatemalans in the timing of growth events, but grow more slowly and grow less
than the Guatemalans, British, or Belgians. Rural Indian, Australian, and African
samples live in environments that delay or retard growth, and these last-named
three samples grow more slowly, delay the onset of the adolescent growth spurt,
and achieve smaller adult height than the Guatemalans. Parameters of the Preece
Baines model are compared between all samples and show that there are several
alternate paths in the rate of growth and the timing of adolescent growth events
that may be taken from childhood to adulthood.
PMID- 28520288
TI - Inference of a gene and its paths of descent: The Newfoundland example.
AB - This paper presents various aspects of Pedigree Analysis through a review of a
study of a Newfoundland genetic isolate. This study has evolved over a number of
years and involved many researchers. The population came to attention due to a
greatly enhanced incidence of a variety of lymphoreticular malignancies. Genetic
analysis shows clearly that there are (at least) two groups of traits. Whereas
the distribution of the leukaemia and lymphosarcoma cases show no clear
genealogical pattern, the existence of a single recessive allele causing
susceptibility to Hodgkin's disease and immunodeficiency in an isolated New
foundland population can be inferred. There appears to be no heterozygote
penetrance, but in the period up to 1974 homozygote penetrance was high and
perhaps complete. More important, the ancestral paths of the allele can be
inferred. Many ancestral individuals are obligatory carriers, and most others
have either probability >95% or <5% of having carried the allele. More recently,
methods were developed and applied in order to investigate linkage of this locus
to conventional blood group and serum protein marker loci. Although no linkages
were found, some observed associations were clarified, and some definite non
linkages established.
PMID- 28520289
TI - Height and weight differences among South African Urban schoolchildren born in
various months of the year.
AB - Among 1,165 subjects aged 6-18 years who were examined once cross-sectionally, a
significant variation in body height and weight according to the month of birth
of the subjects was found. All subjects belonged to the so-called Cape Coloured
community, were born locally, and their parents belonged to the most affluent
sector of the community. Individuals born in February to July were shorter and
weighed less (by 13 to 17% of the standard deviation) than those born in August
to January. These results are similar to those obtained for Canadian children,
who were measured on their birthdays. Since our individuals were measured only
once, at the same time of the year, observed differences cannot be ascribed to
seasonal fluctuations of growth rates prior to measurement but must constitute a
persistent effect of seasonal fluctuation in earlier growth. Immediate
environmental conditions (food, temperature, rainfall, and insolation) in the
Southern Hemisphere fluctuate seasonally 6 months out of phase from those in the
Northern Hemisphere. Thus the similarity of our findings to those from the
Northern Hemisphere suggests a factor common for the entire earth, possibly
related to the ellipsoid shape of the orbit of the planet.
PMID- 28520290
TI - Blood lead levels and growth status of children.
AB - Several studies have shown that elevated blood lead (Pb) levels in children are
associated with decreased growth. Among 139 children aged 1 to 10 years (66 male,
73 female) who attended a Pb clinic in Dallas, Texas, growth was decreased by 1.6
cm in height, 1.4 kg in weight, and 0.6 cm in head circumference for each 10
MUg/dl increase in blood Pb. Consistent with previously reported effects of Pb,
several clinical symptoms (hearing deficit, dental problems, hyperactivity) were
increased in frequency among children with high blood Pb levels (XPb = 34.6
MUg/dl +/- 5.6) compared to the children in the low Pb level group (XPb = 11.9
MUg/dl +/- 3.3). Interestingly, pica was significantly increased in frequency
among children in the high Pb group, indicating oral consumption of non-food
matter was a major source of Pb intoxication. These results suggest that
increased Pb level is an important risk factor for growth deficits in children.
PMID- 28520291
TI - Infant-feeding practices and childhood stature in three ethnic groups.
AB - Inconsistencies in the literature on the relationship of infant feeding practices
to stature were explored in a tri-ethnic sample of 3- or 4-year-old children.
Measures of child stature, maternal stature, child age, type of infant milk
feeding, time of introduction of high fat and high carbohydrate foods, and social
characteristics were analyzed with multivariate statistical techniques. No
statistically significant bivariate or more complex relationships were detected
between the modes of infant-feeding and child stature. The best-fitting
regression equation accounted for 61% of the variance, revealing strong
relationships with child age and maternal height, and weak relationships with
child adiposity, gender, and ethnicity. The present results indicate that there
is little likelihood that metabolic effects induced by methods of infant-feeding
affect stature, at least among 3- or 4-year-old children.
PMID- 28520292
TI - Association of bioelectrical resistance with estimates of fat-free mass
determined by densitometry and hydrometry.
AB - The relationship of whole-body electrical resistance (WBR) to fat-free mass,
derived from densitometry (FFMDb ), hydrometry (FFMTBW ), and densitometric fat
free mass corrected for hydration (FFMD+W ) was investigated in three independent
samples (AZ, IL, CA). Subjects included 75 males and 75 females ranging in age
from 18 to 32 years. Whole-body resistive index (WBRI) computed as height2
/resistance was highly correlated to FFMDb , FFMTBW , and FFMD+W (r = 0.97, 0.95,
and 0.97, respectively). Multiple regression analysis was employed to develop
prediction equations for FFMDb , FFMTBW , and FFMD+W . In each prediction
equation, WBRI was the single best predictor. Accounting for sex and variation in
body weight significantly improved the prediction equations, by increasing the R2
s to 0.95, 0.94, and 0.96 and decreasing the SEEs to 2.6, 3.2, and 2.5 kg, for
FFMDb , FFMTBW , and FFMD+W , respectively. Similarity of the SEEs between
methods (less than 1.0 kg difference) suggests consistency in the precision of
WBRI estimates for body composition.
PMID- 28520293
TI - Dynamic and static measures of growth among pre- and postmenarcheal females in
rural Bangladesh.
AB - Height and weight for age and height and weight velocity are examined in a sample
of Bangladeshi adolescents aged 10-20 years with an average age at menarche of
15.8 years. Interpopulation differences between pre- and postmenarcheal girls are
assessed and age patterns are compared to standards of U.S. and British
adolescents. Bangladeshi adolescents are shorter and lighter for their age and
lighter for their height than are U.S. adolescents. The growth spurt in height
and weight is delayed and spread out over time, and growth rates are lower
throughout the spurt when compared to British and U.S. girls. As in developed
countries, most girls attain menarche after peak height velocity, while weight
gain per year is highest around the time of menarche. There is no significant
relationship between age at menarche and height or weight at menarche.
PMID- 28520294
TI - Differences in the subcomponents of fat-free body in relation to height between
black and white children.
AB - The individual subcomponents of fat-free body (FFB) in relation to height were
investigated in 131 white (N = 85) and black (N = 46) males (MW, MB) and 108
white (N = 63) and black (N = 45) females (FW, FB), aged 8 to 18 years. Bone
mineral content (BM), bone width (BW), and bone mineral index (BMI) were measured
using photon absorptiometry; total body water (TBW) was measured by deuterium
dilution; body density was measured by hydrostatic weighing, correcting for
residual lung volume; and estimates of lean body mass (LBM) were made from total
body potassium (40 K spectroscopy). The subcomponents of the FFB-BM, BW, BMI,
TBW, and K-were regressed on the log of height to determine the exponent of the
independent variable (Ht) that would most accurately predict the dependent
variables (BM, BW, BMI, TBW, K) within gender and race. Regression equations were
derived for each of the variables used to represent a subcomponent of the FFB on
Ht. Significant (P < .05) racial differences were found in BW, with the MB having
wider bones than the MW. Significant racial differences were observed in BMI with
FB demonstrating a greater difference across height than FW. Racial differences
in BM and TBW approached significance within the female sample. At heights
greater than the mean of a typical pubescent child, the males had higher values
for each of the variables, except for BMI, than did the females. The lower BMI
values observed in males indicated that the rate at which male bones grow in
width was greater than their rate of mineralization. Within the male sample,
blacks had higher bone mineral than whites with the magnitude of these
differences dependent on the variable under consideration. Within the female
sample the blacks had greater amounts of BM and BMI in relation to height, while
the whites had a greater amount of K. Therefore, the magnitude of the differences
between blacks and whites in the subcomponents of the FFB are dependent on
gender, stature, and the particular subcomponent of the FFB under consideration.
PMID- 28520295
TI - Estimation of energy expenditure in Western Samoa, American Samoa, and Honolulu
by recall interviews and direct observation.
AB - Reliable and accurate estimates of energy expenditure are a fundamental
requirement for research on energy balance, energy flow, and other biocultural
phenomena. Cross-validation of estimates derived from more than one time
allocation method can detect sources of bias and may lead to estimates which are
more credible than those from activity recalls used alone. This paper compares 24
hour activity recalls and direct observations as methods of estimating the energy
expenditure of 145 18-37-year-old Samoans residing in rural Western Samoa,
American Samoa, and Honolulu. Daily energy expenditure was estimated on 2
workdays by activity recalls (n = 214) or by focal-individual observations (n =
91). Samoan men expend 2,900-3,400 kcal/day and women expend 2,250-2,650
kcal/day. Estimates of energy expenditure in the Western Samoa sample are
comparable to other subsistence horticultural societies, while the American
Samoan and Honolulu samples are comparable to other sedentary working
populations. Group estimates from recall interviews are 100-400 kcal/day higher
than from observations, although this is only a difference of 5-10%.
Overestimation of energy expenditure is more evident at higher work intensities
than for sedentary activities. The apparent exaggeration of strenuous activity in
this, and other, studies indicates that without cross-validation, self-reported
activity data may often be confounded by an unknown amount of subjective bias.
PMID- 28520296
TI - Isonymic analysis of post-famine relationships in the Ards Peninsula, N.E.
Ireland: Effects of geographical and politico-religious boundaries.
AB - During and in the decades after the Irish Famine of 1846 to 1851, the population
of the Ards Peninsula, Co. Down, both declined in numbers and changed in its
composition. In 1863 the surnames of all resident householders were collected as
part of a national valuation. These data have been used to calculate random
isonymy values between civil parishes and the resultant matrix plotted by
nonmetric multidimensional scaling. The results revealed both a major
geographical barrier to gene flow, and politico-religious boundaries in existence
since the early 17th century. The inter-relationships between random isonymy,
geographical distance, and religious denominational frequencies within the
peninsula were investigated by multiple regression analysis. While geographical
influences predominated over short and long distances, in the intermediate
distance range religion played the dominant role. The net effect of these
subdivisions, in combination with famine-associated population losses, would have
been to reduce local effective population sizes significantly, thus enhancing the
potential for genetic drift and random inbreeding.
PMID- 28520297
TI - The Optimal Approach for a Superior Hypogastric Plexus Block.
AB - INTRODUCTION: Superior hypogastric plexus block (SHGPB) is technically difficult,
and an accurate procedure is required to avoid potential complications. We
attempted to determine the reference angles for fluoroscopy-assisted SHGPB and to
establish a predictor as a guide to select the optimal approach between the
classic posterior approach and transdiscal approach. METHODS: Abdominopelvic
computed tomography (CT) scans from 268 patients diagnosed with pelvic
malignancies were examined. The oblique and axial angles needed for the
fluoroscope were measured both for posterior and transdiscal approaches by
simulating the needle trajectory on CT imaging. We developed an SHGPB index
defined by the ratio (%) of the interposterior iliac border distance to the L5
body transverse diameter, which represents the relative transverse diameter of
the bony pelvis. We evaluated whether it can help select the optimal approach for
the SHGPB between the posterior and transdiscal approaches. RESULTS: Males had a
significantly smaller angle than females (right oblique angle for posterior
approach, males 14 [range 12 to 17] degrees vs. females 19 [range 16 to 23]
degrees; P < 0.001). An SHGPB index of < 150 was an independent predictor for
failure of the classic posterior approach (odds ratio 31.3, 95% confidence
interval 5.1 to 104.7). CONCLUSIONS: The optimal right oblique angle of
fluoroscopy for the posterior approach is 13 degrees to 15 degrees in males and
19 degrees to 20 degrees in females. The transdiscal approach may be favored
over the posterior approach when the bony pelvis is narrow relative to the target
vertebral body, which can be measured by the SHGPB index being < 150.
PMID- 28520298
TI - Longitudinal analysis of deciduous tooth emergence in Indonesian children. I.
Life table methodology.
AB - Deciduous tooth emergence was investigated in a sample of 468 children from
central Java. The subjects were examined every 35 days for up to 2 years.
Statistics on the timing of emergence for each tooth were derived from actuarial
life table estimates, and male and female survivorship curves of tooth emergence
were compared for statistical sex differences. Javanese children exhibited
delayed emergence compared to other populations. No overall pattern of sexual
dimorphism was detected, although upper first molars emerged significantly
earlier in females. A comparison of emergence sequence polymorphisms between
Javanese, Finnish, and Japanese children revealed that the i1-i2-m1-c-m2 sequence
is most common in all three populations, but each shows a uniquely higher
proportion of one or more less common polymorphisms.
PMID- 28520300
TI - Is there a selective rural-urban migration in respect to height and weight?
AB - Height and weight were examined in rural-urban premigrants from heavily
depopulating regions in the countryside. The analysis involved children, 5.75
8.74 years, from rural schools in two rural districts in Poland, Bystrzyca
Klodzka and Pinczow, in 1978. Migrants were identified while reexamining the
children in the same schools 10 years later, i.e., in 1988, and by using
information from local census registers. The premigrants from the villages of
Klodzka Pinczow and Pinczow districts do not differ in height and weight when
compared to the total population of rural children examined in each district. The
comparison of height and weight in premigrants and nonmigrants in groups
homogeneous for SES of the children's families indicates that if the SES of rural
families is very low, individuals smaller in size tend to remain in the rural
areas. When SES of the rural population improves, migration of the young seems to
be random in respect to height and weight.
PMID- 28520299
TI - Measurement errors for a portable device measuring short-term growth.
AB - A field trial was conducted for a portable Knee Height Measuring Device (KHMD).
Measurement errors for the machine, within and between observers (intraobserver
and interobserver) and within subjects (intrasubject), were calculated from
repeated observations of two anthropometrists on 40 children, 8 and 9 years of
age. Interobserver technical error (0.452 mm) was larger than that published by
the KHMD developers, but intraclass reliabilities are still very high (0.9975
0.9983). Attained size and fatness of subjects were not significantly correlated
with interobserver measurement errors. Observed errors suggest they are
sufficient to allow detection of knee height growth over periods of time much
shorter than could be accomplished using more conventional anthropometry.
PMID- 28520301
TI - Comparative genetic variance and heritability of head and facial traits in
northwest Indian and Belgian twins.
AB - Genetic variance analysis of 13 head and facial traits is considered in samples
of Northwest, Indian and Belgian twins. Modified t tests, based on the nested
structure of twin data, indicate differences between monozygotic (MZ) and
dizygotic (DZ) mean values of bigonial diameter in Indian females and in Belgian
males, i.e., for only two of 52 instances. Heterogeneity of variance is observed
in about 30% of the craniofacial traits in both samples, invalidating
conventional within-pair genetic variance estimates for these traits. Patterns of
environmental bias on zygosities differ between sexes within the same population
and also between the two samples. Revised average genetic variance ratios are
higher in Indian than in Belgian twins. Male twins manifest, on average, higher
genetic variance ratios than female twins in both the samples. There is stronger
evidence of enviornmental covariance in MZ than in DZ twins for both Indian and
Belgian twins. The pattern of intraclass corrlations, based on average values, is
as follows: ?rMZ > ?rMZ > ?rDZ >= ?rDZ in the Indian twins and ?rMZ > ?rMZ > ?rDZ
> ?rDZ in the Belgian twins.
PMID- 28520302
TI - Malawi maternal and child nutrition study: Study design and anthropometric
characteristics of children and adults.
AB - The Malawi Maternal and Child Nutrition (MMCN) Study is a three-year longitudinal
investigation of some of the determinants and consequences of protein-energy
malnutrition in a rural African population. This paper describes the
anthropometric characteristics of children and adults based on the baseline
census conducted in the 89 villages included in the MMCN Study. Mean length-for
age of Malawian children (birth-60 months) is very low (Z-score = -2.21) and,
unlike most other populations, continues to decline with advancing age. Weight
for-length is more nearly normal (mean Z-score = -0.21) but shows the same age
related decline between birth and 18 months (and subsequent return to normal
levels) as that seen in many other developing countries. This age pattern is also
reflected in upper arm anthropometry, notably estimated arm fat area. Length-for
age and weight-for-age of children is associated with birthweight in the 40% of
children having health cards, but body composition indicators do not show the
same consistent association with birthweight at all ages. Adult men and women
have very low skinfold thicknesses relative to U.S. blacks (50-60% of U.S.
medians at the triceps and subscapular sites). Estimated upper arm cross
sectional muscle (plus bone) area for Malawian men averages 74% of U.S. white
values, while that for women averages 100% of U.S. white values.
PMID- 28520303
TI - Influence of chronic sublethal cyanide on body weight in neonatal swine:
Implications for humans consuming cassava (Manihot esculenta).
AB - The consumption of CN- containing foods (particularly cassava) is pervasive among
millions of humans throughout the tropics, yet very little is known about the
long-term implications of this dietary pattern on growth. In this study Liberian
(West African) levels of dietary cyanide (CN- ) intakes were replicated in
juvenile swine for 24 weeks to quantify the effects of specified, chronic,
sublethal doses of this metabolic poison on body weight. Twelve female and male
littermates were partitioned into a control (O mg CN- ) and 3 treatment groups
(1.2, 0.7, or 0.4 mg CN- per kg body weight per day). CN- treatments depressed
absolute weight gain in a dose-dependent manner with significant differences
apparent as early as week 12. Thyroid hormones T3 and T4 and fasting blood
glucose values were evaluated at 6-week intervals. T3 levels were ostensibly
suppressed and blood glucose values elevated with increasing CN- ingestion. Serum
thiocyanate (SCN- ), the major metabolite of sublethal CN- ingestion, was
positively correlated with CN- intake loads (r = 0.83, P < 0.01). Hypothesized
physiological foundations for these observations and theoretical implications for
human growth are elaborated.
PMID- 28520304
TI - Hemoglobin concentration and working capacity of nonpregnant rural women of the
Kathmandu valley of Nepal.
AB - The relationship between hemoglobin concentration, nutritional status, and
working capacity of village women in Nepal was investigated. Subjects were 71
nonpregnant women (ages 18 to 60 yr) living at altitudes ranging from 1,300 to
1,600 m in a rural area near Kathmandu. Half of the women (51%) performed manual
wage labor on a daily basis, working as field hands during the agricultural
season and breaking rocks into gravel during the remainder of the year; the
remaining 49% worked only in their own fields or in exchange labor groups. Anemia
was mild but widespread; 62% of the women had hemoglobin concentrations of 12.0
gm/dl or lower. Mean hemoglobin for the total sample was 11.7 +/- 1.4 gm/dl
(range 7.2 to 15.6 gm/dl). A step test was used to measure working capacity, and
expired air samples were analyzed for O2 and CO2 using a Scholander 0.5 ml gas
analyzer. Caste and ethnic groups differed significantly with respect to
hemoglobin concentration (P < 0.005) and heart rate response to submaximal
exercise (P < 0.001), but not in anthropometric measurements. Among those ethnic
groups accustomed to daily physical labor, i.e., the Newars and Tamangs, lower
hemoglobin concentration was correlated significantly with higher heart rate,
higher oxygen uptake, and lower mechanical efficiency during submaximal aerobic
exercise.
PMID- 28520305
TI - Family resemblance for patterns of growth in early childhood.
AB - Parameters of the Jenss curve representing linear and non-linear components of
growth in early childhood were fitted to longitudinal recumbent length and weight
measurements from participants in the Fels Longitudinal Growth Study. Nuclear
family correlations were estimated for each of four Jenss parameters (a linear
intercept and slope and a non-linear intercept and degree of curve) for length
and for weight. The TAU path model was fit to the correlations, in order to
estimate path coefficients representing transmissibility from parent to child (t2
) and non-transmissible sibling resemblance (s). Likelihood ratio chi2 tests
suggest that significant family resemblance exists for each Jenss parameter for
both variables. Transmissibility is the major component in family resemblance for
the linear and non-linear intercepts for length, whereas non-transmissible
sibling environmental effects are dominant for three of the four weight
parameters. The source of the family resemblance for the remaining parameters
could not be pinpointed. The linear slope and degree of curve for weight are more
similar for same sex siblings than for opposite sex pairs, suggesting that the
degree of shared sibling environment affecting the shape of the growth curve for
weight may be greater for same sex pairs.
PMID- 28520306
TI - Sex differentials in unintentional injury mortality in relation to age at death.
AB - Sex differentials in unintentional injury mortality were examined using death
records for New York State residents that died as the result of an unintentional
injury between the years 1984 and 1988 (n = 22,547). Male/female ratios were
computed for nine age groups and for the four leading causes of unintentional
injury death: motor vehicle incidents, falls, fire, and drowning. Male mortality
is significantly higher than female mortality for all causes (P < 0.05). The age
specific pattern of mortality varies among the four causes of death examined, but
the age-specific pattern of male/female mortality ratios is consistent among all
four causes. All four leading causes of unintentional injury death show a peak in
relative male risk in young adulthood (usually between 15 and 24 years of age).
This common peak may reflect increased risk associated behaviors of young males,
including alcohol. Two causes of death, motor vehicle incidents and fire, show a
second peak in relative male risk among the elderly (75+ years), perhaps
reflecting sex differences in alcohol and tobacco use.
PMID- 28520307
TI - Human Biology Council.
PMID- 28520308
TI - Altitude and growth among the sherpas of the eastern Himalayas.
AB - The results of the anthropometric survey of Sherpa children of both sexes (n =
478) from high- and low-altitude areas in the eastern Himalayas are presented.
The study reveals that growth is slower both more prolonged in the high-altitude
Sherpas compared with growth at low altitude and that Sherpa children are the
smallest of all the high-altitude populations considered here. Sexual dimorphism
is not well defined during the earlier age periods. Our skinfold thickness data
from the low-altitude Sherpas corroborate the centripetal distribution of fat
found elsewhere.
PMID- 28520310
TI - Editorial.
PMID- 28520309
TI - Model fitting to early childhood length and weight data from the fels
longitudinal study of growth.
AB - Length and weight data from 3 months to 6 years of age from 466 participants in
the Fels Longitudinal Study of Growth were used to fit the Jenss non-linear
growth curve. Six (1%) of the Fels participants had extremely outlying values for
length parameters, and 20 (4%) had outlying values for weight parameters. The
general pattern in the outliers is for average or below average size in infancy,
followed by unusually rapid growth or weight gain in childhood. This outlier
pattern is associated with significantly higher mean stature or weight at 18
years of age. The results for the majority of the participants are similar to
those found in 229 children from the Harvard Growth Study, except for the non
linear intercept for length and the linear intercept for weight. Significant sex
differences have not previously been reported for Jenss parameters, perhaps
because previous applications have used much smaller sample sizes.
PMID- 28520311
TI - Estimation of total body water by bioelectrical impedance analysis in blacks.
AB - Several differences exist between the body composition of blacks and whites. This
study was designed to investigate the applicability of bioelectrical impedance
analysis (BIA) in blacks, using prediction equations developed in whites. A
multiple regression equation developed on 79 white adults, using deuterium oxide
dilution space total body water (D2 O-TBW) as the reference method, was
prospectively applied to 88 blacks aged 19-50 years. Although the regression line
of D2 O-TBW on BIA-TBW was not significantly different from the line of identity
(r = 0.98, SEE = 1.71 liters), mean TBW was significantly underestimated by 0.84
liter. Other BIA equations from the literature also underestimated D2 O-TBW in
blacks, except for an equation developed on a mixed black and white population.
Multiple regression analysis on the data of the black and white subjects combined
showed that race, offered as a separate independent variable, improved the
correlation with D2 O-TBW slightly but significantly (P < 0.01). It was concluded
that BIA may be valuable in the assessment of body composition in blacks as well
as in whites. In this study a small underestimation of TBW occurred in blacks,
using (BIA) equations from whites. This may be due to racial differences in body
composition or to factors unrelated to ethnicity.
PMID- 28520312
TI - Differentially delayed development in the hand-wrist skeletons of children with
cystic fibrosis: Round versus tubular bones.
AB - From a sample of 50 cystic fibrosis patients in whom a previous study had
demosntrated a lack of statistical interdependence between disease severity and
significant TW2-20 bone age delays, hand-wrist radiographs for a preadolescent
subsample of 30 (14 females and 16 males, 7.4 to 13.0 years of age) are
reassessed using the TW2 method to (1) elucidate any significant differences in
maturational delays exhibited by the carpals and the tubular bones (radius, ulna,
and short bones [RUS]) of the hand-wrist complex and (2) assess the relationships
between the clinically derived measure of pulmonary disease severity,
anthropometric indices of nutritional status, and the bone age delays in these
two regions. Female and male carpal bone age delays, pulmonary disease severity
scores, and weight/height2 differ significantly. However, both sexes exhibit
significant mean TW2-carpal bone age delays, while mean TW2-RUS ages are either
non-significantly delayed or advanced with respect to normative standards.
Correlation and all-subsets multiple linear regression analyses reveal no
significant interdependence or predictive relationships between clinically
derived measures of pulmonary disease severity and anthropometric measures of
nutritional complications and delayed skeletal maturation in either the carpals
or tubular bones of the hand-wrist complex.
PMID- 28520313
TI - Inheritance of longevity evinces no secular trend among members of six New
England families born 1650-1874.
AB - This study investigated the historical trend in resemblance between first-degree
relatives for age at death. Data from genealogies of six New England families (N
= 13,656) were divided into nine 25 year birth cohorts, 1650-1874, to test the
hypothesis that familial influence on human longevity has changed during the past
300 years. Heritability (h2 ) for longevity demonstrated no historical trend,
whether calculated by regression of offspring's longevity on paternal, maternal,
or mid-parental longevity or by intraclass correlations (t) among sibships.
Ninety-five percent confidence intervals (C.I.) for h2 (additive genetic
variance) were in the range 0.10-0.33 for parent-offspring regressions and 0.16
0.22 based on mean of sibship regressed on mean of parents. Based on sibship t,
the 95% C.I. for the upper limit to h2 (which includes variance contributions
caused by dominance interactions and common developmental environment as well as
additive genetic effects) was 0.33-0.41. In this socially elite sample, the
statistical contribution of first-degree relatives to age at death has varied
within a historically consistent range over the past 300 years, directly implying
a persistent genetic influence on longevity. The magnitude of this influence with
respect to additive genetic variance, about 10-30%, may overestimate h2 because
of the elite nature of the sample. Nevertheless, these results support a genetic
component to lifespan even though the majority of variation in human longevity is
not explained by genetic factors.
PMID- 28520314
TI - Twin study of digital dermatoglyphic traits: Investigation of heritability.
AB - Digital patterns of a sample of monozygotic and dizygotic twins were analyzed to
obtain heritability values for the four basic types of patterns: arch, tented
arch, loops, and whorls. Loops have been separated according to their orientation
radial or ulnar. To carry out this study, we used the Holzinger and Clark
indices. The results show highest concordances for monozygotic twins except for
ulnar loops of the left hand and radial ones of the right hand. Different values
of heritability were found for the right and left hands, with finger I having the
highest values.
PMID- 28520315
TI - Adiposity and age of menarche in Hispanic women.
AB - Women with increased adiposity have been shown to have earlier menarche. However,
the association between menarche and body fat distribution has been
controversial. The present study examined relationships between several
anthropometric data and age at menarche in 2,494 women aged 25 to 74 years from
the Hispanic Health and Nutrition Examination Survey. Early menarche was
similarly related to adiposity as measured by body mass index (BMI), skinfolds
representative of central adiposity (subscapular and iliac), and skinfolds
representative of peripheral adiposity (triceps and calf). These relationships
persisted after controlling for a variety of influences such as socioeconomic
status; they were consistent in all three ethnic groups studied, but were
significant only in Puerto Rican women. Ratios of central/peripheral skinfold
measures were not associated with menarche. These analyses describe the
relationship between early maturation and overall adiposity in three distinct
Hispanic groups and reject a specific association between menarche and central
body fat distribution.
PMID- 28520317
TI - A Very Different Paradigm for Living Kidney Donor Risk.
PMID- 28520316
TI - The Living Donor Collective: A Scientific Registry for Living Donors.
AB - In the setting of an overall decline in living organ donation and new questions
about long-term safety, a better understanding of outcomes after living donation
has become imperative. Adequate information on outcomes important to donors may
take many years to ascertain and may be evident only by comparing large numbers
of donors with suitable controls. Previous studies have been unable to fully
answer critical questions, primarily due to lack of appropriate controls,
inadequate sample size, and/or follow-up duration that is too short to allow
detection of important risks attributable to donation. The Organ Procurement and
Transplantation Network does not follow donors long term and has no prospective
control group with which to compare postdonation outcomes. There is a need to
establish a national living donor registry and to prospectively follow donors
over their lifetimes. In addition, there is a need to better understand the
reasons many potential donors who volunteer to donate do not donate and whether
the reasons are justified. Therefore, the US Health Resources and Services
Administration asked the Scientific Registry of Transplant Recipients to
establish a national registry to address these important questions. Here, we
discuss the efforts, challenges, and opportunities inherent in establishing the
Living Donor Collective.
PMID- 28520318
TI - [Image of the month. A pediatric case of unilateral proptosis and cystic
lymphangioma.]
PMID- 28520319
TI - [How I treat... a neonatal Herpes simplex virus infection].
AB - Neonatal herpes simplex virus infection is rare but important to recognize
because of the major risk of sequelae or death. The diagnosis is mainly based on
specific clinical and biological analyses. Aciclovir is the treatment of choice,
duration of administration depending on the severity of the disease. A six-month
treatment with suppressive-dose oral aciclovir is recommended to improve the
child's prognosis. From a clinical case, we reviewed the literature to improve
the management.
PMID- 28520320
TI - [Pathergic postsurgical-induced Pyoderma gangrenosum].
AB - Pyoderma gangrenosum (PG) is a rare pustular and ulcerative inflammatory disease
belonging to the group of neutrophilic dermatoses. It is frequently associated
with systemic immune diseases. In this context the PG can be exceptionally
triggered by tissue trauma such as surgery (pathergy). We report the case of a
patient with stabilized rheumatoid arthritis who developed aggressive and
disseminated PG at all surgical wounds following an abdominal dermolipectomy
associated with breast pexy. Systemic corticosteroid methylprednisolone allowed a
rapid control of skin ulcerations. In the aftermath of an intervention, PG is
often confused with a bacterial skin-necrotizing panniculitis. The recognition of
the inflammatory nature of cutaneous symptoms is crucial to quickly start an
immunosuppressive treatment and limit scarring sequelae. Our case also
illustrates the need to consider any history of dysimmune inflammatory or
oncohematological disease as a risk factor before surgery, even if the latter are
stabilized.
PMID- 28520321
TI - [Multifocal osteonecrosis revealing an antiphospholipid syndrome : case report].
AB - This article illustrates the case of a 30-year-old woman presenting with
multifocal osteonecrosis as the first symptom of a primary antiphospholipid
syndrome. The association of multifocal osteonecrosis and primary
antiphospholipid syndrome without any medical history of vascular thrombosis or
pregnancy complications remains rare.
PMID- 28520322
TI - [Psychological impact of out-of-hospital cardiopulmonary resuscitation (CPR) on
the witness engaged in gestures of survival].
AB - The occurrence of an unexpected sudden death puts the witnesses of this event in
a situation of high emotional impact. The benefit to allow the families of
victims to dispense the first resuscitation techniques has been emphasized.
However, little data exist on the emotional impact of a cardio-respiratory arrest
outside the hospital on the witness, who is often a close family member.
Recently, we investigated the presence of psychological distress and the factors
influencing it, in the active practice of basic resuscitation gestures by the
witnesses guided by the operator 112. Resuscitation by a person not belonging to
the medical corps seems not to be devoid of psychological impact. Indeed, the
presence of psychological distress is observed for most of witnesses questioned 6
to 10 days after the call but also 3 months later. This work highlights therefore
the importance of identifying the coping strategies involved, in order to promote
potentially beneficial strategies and limit the trauma associated with this type
of event.
PMID- 28520323
TI - [Asthma and obesity].
AB - Asthma and obesity are both common diseases in western world. According to the
data from our asthma clinic 20 % of our patients are obese and this rate
increases up to 25 % in severe asthmatics included in the Belgian Severe Asthma
national Registry. Alteration of thoracic mechanics contributes to greater
symptom burden and poor asthma control in obese asthmatics. In particular the
response to inhaled corticoids is attenuated. Weight loss results in a dramatic
improvement in asthma control and should be a major goal in the asthma management
of these patients.
PMID- 28520324
TI - [Professional fatigue syndrome (burnout). Part 1 : identification by the general
practitioner].
AB - Burnout or professional fatigue syndrome has never been more talked about than in
recent times. It is the result of exposure to a situation in which the strategies
of the subject who are supposed to manage the stresses of the environment become
outdated and inoperative. An imbalance is created between the demands and the
material, operational and psychological resources to cope with them. Many health
professions are confronted with the challenge of managing burnout. Among them,
the general practitioner is very often on the front line. This paper is dedicated
to him in priority. In its first part, it deals successively with the
classification of the pathology (ICD-10 and DSM-5), its prevalence, its socio
economic impacts, its clinical picture (three stages), its diagnosis (by clinic
and questionnaires), its causes, its evolution (from denial to acceptance), and
its long-term consequences in the absence of treatment.
PMID- 28520325
TI - [Newborn infants' first outpatient visit].
AB - The focus on outpatient follow-up of newborn infants increases as the duration of
hospital stay after birth decreases. The first outpatient visit addresses the
adequacy of the home transition. Appropriate feedings are checked. Sudden infant
death syndrome prevention and security advices are reminded. Realisation of both
neonatal dried blood screen and hearing test is confirmed, as well as planning of
specific follow-up appointments. The physical exam will focus on red flags for
diseases or malformations with a delayed presentation.
PMID- 28520326
TI - [Bipressil(r) : first single-pill combination of bisoprolol and perindopril
arginine].
AB - In patients suffering from systemic arterial hypertension, coronary artery
disease, or heart failure, beta-blockers and angiotensin-convertase enzyme
inhibitors play a major therapeutic and preventive role. Coronary artery disease
remains the leading cause of mortality in industrialized countries. Unless
adapted preventive strategy, notably pharmacological interventions,
cardiovascular events in these patients remain high. One reason for this relative
failure is represented by non-adherence to treatment. A treatment consisting in
an association in one pill of several different molecules should confer a higher
treatment compliance and thus efficacy. This article describes the
characteristics of the first available dual association between a cardioselective
beta-blocker agent, bisoprolol, and an angiotensin-convertase enzyme inhibitor,
perindopril arginine.
PMID- 28520327
TI - [Importance of stopping some medications in case of gastrointestinal disturbances
leading to dehydration].
AB - This clinical case draws attention to the importance of stopping some medications
in case of gastrointestinal disturbances that could induce dehydration. The
latter can provoke an acute renal failure, which may lead to a toxic accumulation
of these pharmacological agents and/or increase their nephrotoxicity. This may
induce a vicious circle that is potentially dangerous and even fatal. Three
pharmacological classes that are widely used in clinical practice are considered
as examples, metformin, inhibitors of the renin-angiotensin system and
nonsteroidal anti-inflammatory drugs. For each of them, the pathophysiology of
the complication will be briefly discussed. Some patient risk profiles where
caution is mandatory will be also emphasized.
PMID- 28520328
TI - Identification and Localization of beta-D-Glucosidasefrom Two Typical Oenococcus
oeni Strains.
AB - beta-D-glucosidase (betaG) gene from Oenococcus oeni SD-2a and 31MBR was cloned,
sequenced and analyzed, also intracellular betaG of the two strains was further
localized. The results showed that betaG gene of the two strains was in high
homology (> 99%) to reported betaG gene, confirming both strains possess betaG
activity at the molecular level. Intracellular betaG of SD-2a is a mainly soluble
protein, existing mostly in the cytoplasm and to some extent in the periplasm.
While for 31MBR, intracellular betaG is mainly insoluble protein existing in the
cytoplasmic membrane. This study provides basic information for further study of
the metabolic mechanism of betaG from O. oeni SD-2a and 31MBR.
PMID- 28520329
TI - Characterization of Staphylococcal Cassette Chromosome mec (SCCmec)in Methicillin
Resistant Staphylococcus epidermidis Strains Isolatedfrom Biomaterial-Associated
Infections and their Antibiotic Resistance Patterns.
AB - This work aims to provide an insight into staphylococcal cassette chromosome mec
elements and antibiotic resistance in clinical isolates of Staphylococcus
epidermidis. The dominating type was SCCmec - IV. Fifteen isolates were assigned
to SCCmec type III, two isolates to SCCmec type II. Most isolates were resistant
to at least three of the non-beta-lactam antibiotics tested. None of the strains
exhibited resistance to new generation antibiotics, such as daptomycin and
linezolid. Also, none of these strains showed resistance to tigecycline and only
four strains were resistant to rifampin i.e. antibiotics which are very efficient
in treating biofilm-associated infections.
PMID- 28520330
TI - Qualitative and Quantitative Characteristics of Selected Bacterial Groupsin
Children with Inflammatory Bowel Diseases.
AB - The aim of the study was evaluation of qualitative and quantitative changes in
bacterial ecosystem in 109 children with inflammatory bowel diseases. Stools
obtained from patients were analysed for selected bacteria and concentration of
faecal inflammatory markers (calprotectin, lactoferrin, M2-PK). The number of
selected microorganisms depends on the level of clinical activity of disease and
is correlated with faecal concentration of inflammatory markers. Differences in
microflora disturbance, observed in patients with Crohn's disease and ulcerative
colitis, may suggest different causes of development of both pathologies.
PMID- 28520331
TI - Cytotoxic and Bacteriostatic Activity of Nanostructured TiO(2) Coatings.
AB - Nanostructures are structures, mainly synthetic (nanosurfaces, cylindrical
nanotubes, and nanospheres), which range between 1-100 nm in at least one
dimension and can be engineered to a wide range of physical properties. This
paper aims to explore the bacteriostatic and cytotoxic characteristics of nano
TiO(2) coated specimens of glass, stainless steel and ceramic with different
thickness and roughness. The results show that stainless steel and glass
specimens with a nano-TiO(2) coating thickness of 200 nm have a bacteriostatic
effect of 97% and 100%, respectively after 30 minutes of UV exposure. Glass
specimens with a nano-TiO(2) coating thickness of 750, 200 and 50 nm have a
bacteriostatic effect of 86%, 93% and 100% after 60 minutes. Nano-TiO(2) coatings
show a great bacteriostatic but not a cytotoxic effect, thus representing a
valuable alternative for biomedical applications.
PMID- 28520333
TI - Monitoring of Virulence Genes, Drug-Resistance in Campylobacter coli Isolatedfrom
Golden Retrievers.
AB - The investigation was performed on 75 of Golden Retriever puppies. Faecal samples
were collected on the 42 day of the puppies life (control). Probiotic preparation
was administered on 43 day of the puppies life and 10 days after the application
of the probiotic, faecal samples were collected again (on 53 day of puppies
life). All isolates of Campylobacter coli isolated prior to the administration of
the probiotic were found to contain the cadF gene responsible for adhesion, as
well as, the flaA gene influencing motility of the examined bacteria. Significant
differences (P < 0.05) were recorded only in the case of enrofloxacin.
PMID- 28520332
TI - Enteroviruses Associated with Aseptic Meningitis in Poland, 2011-2014.
AB - A 4-year study (2011-2014) of patients with meningitis was performed. Out of the
686 cerebrospinal fluid samples, 465 (67.8%) were positive for eneteroviruses
using RT-PCR and out of 334 clinical samples, 216 (64.7%) were positive for
enteroviruses using cell culture methods. The highest detection rate was observed
in the summer and autumn. In total, 185 enteroviruses were identified by using
neutralization test. Echovirus 6 and 30 were the most common (41.7% and 37.5%
respectively). The highest frequency of neurological infections (32.7%) occurred
in children aged 5-9 years, mostly males (63.9%).
PMID- 28520334
TI - Kidney anatomy: three dimensional (3D) printed pelvicalyceal system models of the
collector system improve the diagnosis and treatment of stone disease.
PMID- 28520335
TI - PRISMA statement and PROSPERO.
PMID- 28520336
TI - PDE-5 inhibitors should be used post radical prostatectomy as erection function
rehabilitation? | Opinion: Yes.
PMID- 28520338
TI - Re: Artificial urinary sphincter for urinary incontinence after radical
prostatectomy: a historical cohort from 2004 to 2015.
PMID- 28520386
TI - Pneumococcal vaccine--past, present and future.
PMID- 28520337
TI - PDE-5 inhibitors should be used post radical prostatectomy as erection function
rehabilitation? | Opinion: No.
PMID- 28520339
TI - REPLY BY THE AUTHORS: Re: Artificial urinary sphincter for urinary incontinence
after radical prostatectomy: a historical cohort from 2004 to 2015.
PMID- 28520387
TI - Pneumococcal infection: update.
PMID- 28520388
TI - Immunological mechanism in the pathogenesis of pneumococcal pneumonia and in the
effectiveness of anti-pneumococcal vaccines.
PMID- 28520389
TI - Characteristics and Differences in Pneumococcal Vaccines: 1. Polysaccharide
vaccine.
PMID- 28520390
TI - Characteristics and Differences in Pneumococcal Vaccines; 2. Pneumococcal
conjugate vaccine.
PMID- 28520391
TI - Reaction Layer Imaging Using Fluorescence Electrochemical Microscopy.
AB - The chemical confinement of a pH sensitive fluorophore to a thin-reaction layer
adjacent to an electrode surface is explored as a potentially innovative route to
improving the spatial resolution of fluorescence electrochemical microscopy. A
thin layer opto-electrochemical cell is designed, facilitating the visualization
of a carbon fiber (diameter 7.0 MUm) electrochemical interface. Proton
consumption is driven at the interface by the reduction of benzoquinone to
hydroquinone and the resulting interfacial pH change is revealed using the
fluorophore 8-hydoxypyrene-1,3,6-trisulfonic acid. It is demonstrated that the
proton depletion zone may be constrained and controlled by the addition of a
finite acid concentration to the system. Simulation of the resulting fluorescence
intensity profiles is achieved on the basis of a finite difference model, with
excellent agreement between the theoretical and experimental results.
PMID- 28520392
TI - Gold Nanostar Enhanced Surface Plasmon Resonance Detection of an Antibiotic at
Attomolar Concentrations via an Aptamer-Antibody Sandwich Assay.
AB - A new sandwich assay for tetracycline (TC) involving a DNA aptamer and antibody
pair is demonstrated in conjunction with gold nanostar (GNS) enhanced surface
plasmon resonance (SPR) to achieve detection in the low attomolar range. GNS
particles were covalently functionalized with the antibody probe (antiTC) and
integrated into a surface sandwich assay in conjunction with a SPR gold chip
modified with the TC-specific aptamer. After it was demonstrated that both
affinity probes can bind simultaneously to TC, optimization of the assay was
performed using either antiTC only or GNS-antiTC conjugates to interact with
aptamer/TC complexes present on the chip surface. Target concentrations as low as
10 aM could be detected using GNS-antiTC's, which was >103 times greater in
performance than when using antiTC only. In addition, good selectivity was
achieved with respect to other tetracycline derivative antibiotics, such as
oxytetracycline (OTC) and chlortetracycline (CTC), both which are structurally
similar to TC. As a demonstration of trace antibiotic analysis in environmental
samples, the GNS enhanced sandwich assay was applied to analyze TC added to
aliquots of local river water and the results validated by comparing to
conventional high-performance liquid chromatography (HPLC) analysis.
PMID- 28520394
TI - In Vitro Metabolic Engineering of Amorpha-4,11-diene Biosynthesis at Enhanced
Rate and Specific Yield of Production.
AB - In vitro metabolic engineering is an alternative approach to cell-based
biosynthesis. It offers unprecedented flexibility for the study of biochemical
pathways, thus providing useful information for the rational design and assembly
of reaction modules. Herein, we took the advantage of in vitro metabolic
engineering to initially gain insight into the regulatory network of a
reconstituted amorpha-4,11-diene (AD) synthetic pathway. Guided by lin-log
approximation, we rapidly identified the hitherto unrecognized inhibition of
adenosine triphosphate (ATP) on both farnesyl pyrophosphate synthase (FPPS) and
amorpha-4,11-diene synthase (ADS). Furthermore, the byproduct, pyrophosphate
(PPi), potently inhibits ADS, but not FPPS. To lower the inhibition, an ATP
recycling system and pyrophosphatase were used and resulted in a significant (~3
fold) enhancement in the rate of AD production (~5.7 MUmol L-1 min-1). A
coimmobilized multienzyme reaction system was then developed to recycle the
enzymes. When inhibitory metabolites concentrations were reduced, the specific
enzymatic yield of AD was further enhanced (>6-fold). This study demonstrated
that mitigating the accumulation of inhibitory metabolites can result in higher
yields of AD production by in vitro multienzymatic reactions.
PMID- 28520396
TI - Simultaneous Online Monitoring of Multiple Reactions Using a Miniature Mass
Spectrometer.
AB - Advances in chemical sampling using miniature mass spectrometer technology are
used to monitor slow reactions at a frequency of ca. 180 h-1 (on the Mini 12)
with no sample carryover and with inline derivatization in the case of poorly
ionizing compounds. Moreover, we demonstrate high reproducibility with a relative
error of less than 10% for major components. Monitoring is enabled using a
continuous-flow nanoelectrospray (CF-nESI) probe contained in a custom-built 3D
printed rotary holder. The holder position is automatically set using a stepper
motor controlled by a microcontroller. Reaction progress of up to six reactions,
including hydrazone formation and Katritzky transamination, can be monitored
simultaneously without carryover for several hours.
PMID- 28520395
TI - Tricyclic Spirolactones as Modular TRPV1 Synthetic Agonists.
AB - TRPV1 is a prominent signal integrator of the pain system, known to be activated
by vanilloids, a family of endogenous and exogenous pain-evoking molecules,
through the vanilloid-binding site (VBS). The extensive preclinical profiling of
small molecule inhibitors provides intriguing evidence that TRPV1 inhibition can
be a useful therapeutic approach. However, the dissimilarity of chemical species
that activate TRPV1 creates a major obstacle to understanding the molecular
mechanism of pain induction, which is viewed as a pivotal trait of the
somatosensory system. Here, we establish the existence of a unique family of
synthetic agonists that interface with TRPV1 through the VBS, containing none of
the molecular domains previously believed to be required for this interaction.
The overarching value obtained from our inquiry is the novel advancement of the
existing TRPV1 activation model. These findings uncover new potential in the area
of pain treatment, providing a novel synthetic platform.
PMID- 28520393
TI - Universal and Quantitative Method To Evaluate Inhibitor Potency for Cysteinome
Proteins Using a Nonspecific Activity-Based Protein Profiling Probe.
AB - Recently, there have been a limited number of new, validated targets for small
molecule drug discovery in the pharmaceutical industry. Although there are
approximately 30 000 genes in the human genome, only 2% are targeted by currently
approved small-molecule drugs. One reason that many targets remain neglected by
drug discovery programs is the absence of biochemical assays enabling evaluation
of the potency of inhibitors in a quantitative and high-throughput manner. To
overcome this issue, we developed a biochemical assay to evaluate the potency of
both reversible and irreversible inhibitors using a nonspecific thiol-labeling
fluorescent probe. The assay can be applied to any targets with a cysteine
residue in a pocket that can accommodate small-molecule ligands. By constructing
a mathematical model, we showed that the potency of compounds can be
quantitatively evaluated by performing an activity-based protein profiling assay.
In addition, the validity of the theory was confirmed experimentally using
epidermal growth factor receptor kinase as a model target. This approach provides
an assay system for targets for which biochemical assays cannot be developed. Our
approach can potentially not only expand the number of exploitable targets but
also accelerate the lead optimization process by providing quantitative structure
activity relationship information.
PMID- 28520397
TI - Laser-Induced Graphene Layers and Electrodes Prevents Microbial Fouling and
Exerts Antimicrobial Action.
AB - Prevention of fouling on surfaces is a major challenge that broadly impacts
society. Water treatment technologies, hospital infrastructure, and seawater
pipes exemplify surfaces that are susceptible to biofouling. Here we show that
laser-induced graphene (LIG) printed on a polyimide film by irradiation with a
CO2 infrared laser under ambient conditions is extremely biofilm resistant while
as an electrode is strongly antibacterial. We investigated the antibacterial
activity of the LIG surface using LIG powder in suspension or deposited on
surfaces, and its activity depended on the particle size and oxygen content.
Remarkably, the antimicrobial effects of the surface were greatly amplified when
voltages in the range of 1.1-2.5 were applied in an electrode configuration in
bacterial solutions. The bactericidal mechanism was directly observed using
microscopy and fast photography, which showed a rapid bacterial movement toward
the LIG surface and subsequent bacterial killing. In addition, electrochemical
generation of H2O2 was observed; however, the bacterial killing mechanism
depended strongly on the physical and electrical contact of the bacterial cells
to the surfaces. The anti-biofilm activity of the LIG surfaces and electrodes
could lead to efficient protection of surfaces that are susceptible to biofouling
in environmental applications by incorporating LIG onto the surfaces.
PMID- 28520399
TI - Immunofluorescence Imaging Strategy for Evaluation of the Accessibility of DNA 5
Hydroxymethylcytosine in Chromatins.
AB - DNA 5-hydroxymethylcytosine (5hmC) is an important epigenetic modification found
in various mammalian cells. Immunofluorescence imaging analysis essentially
provides visual pictures for the abundance and distribution of DNA 5hmC in single
cells. However, nuclear DNA is usually wrapped around nucleosomes, packaged into
chromatins, and further bound with many functional proteins. These
physiologically relevant events would generate barriers to the anti-5hmC antibody
to selectively recognize 5hmC in DNA. By taking advantage of these naturally
generated barriers, here, we present a strategy to evaluate the accessibility of
DNA 5hmC in chromatins in situ. We demonstrate that a few of the 5hmC sites in
DNA are exposed or accessible to anti-5hmC antibody under nondenaturing
conditions, suggesting that these 5hmC sites are not covered by functional DNA
binding proteins in mouse embryonic stem cells. Consistently, these 5hmC foci
were distributed in open euchromatin regions as revealed by the 4',6-diamidino-2
phenylindole (DAPI) staining. By overexpressing TET1 catalytic domain
(responsible for oxidation 5mC to produce 5hmC) in human MCF-7 cells, we observed
a significant increase in accessible 5hmC along with an increase in total 5hmC
sites. Collectively, by the use of the nondenaturing immunofluorescence imaging
approach, we could obtain a visual landscape on the accessibility of DNA 5hmC in
chromatins.
PMID- 28520400
TI - Femtomole-Scale High-Throughput Screening of Protein Ligands with Droplet-Based
Thermal Shift Assay.
AB - There is a great demand to measure protein-ligand interactions in rapid and low
cost way. Here, we developed a microfluidic droplet-based thermal shift assay
(dTSA) system for high-throughput screening of small-molecule protein ligands.
The system is composed of a nanoliter droplet array chip, a microfluidic droplet
robot, and a real-time fluorescence detection system. Total 324 assays could be
performed in parallel in a single chip with an 18 * 18 droplet array. The
consumption of dTSA for each protein or ligand sample was only 5 nL (femtomole
scale), which is significantly reduced by over 3 orders of magnitude compared
with those in 96- or 384-well plate-based systems. We also observed the
implementation of TSA in nanoliter droplet format could substantially improve
assay precision with relative standard deviation (RSD) of 0.2% (n = 50), which
can be ascribed to the enhanced thermal conduction in small volume reactors. The
dTSA system was optimized by studying the effect of droplet volumes, as well as
protein and fluorescent dye (SYPRO Orange) concentrations. To demonstrate its
potential in drug discovery, we applied the dTSA system in screening inhibitors
of human thrombin with a commercial library containing 100 different small
molecule compounds, and two inhibitors were successfully identified and
confirmed.
PMID- 28520398
TI - Multiple States of Nitrile Hydratase from Rhodococcus equi TG328-2: Structural
and Mechanistic Insights from Electron Paramagnetic Resonance and Density
Functional Theory Studies.
AB - Iron-type nitrile hydratases (NHases) contain an Fe(III) ion coordinated in a
characteristic "claw setting" by an axial cysteine thiolate, two equatorial
peptide nitrogens, the sulfur atoms of equatorial cysteine-sulfenic and cysteine
sulfinic acids, and an axial water/hydroxyl moiety. The cysteine-sulfenic acid is
susceptible to oxidation, and the enzyme is traditionally prepared using butyric
acid as an oxidative protectant. The as-prepared enzyme exhibits a complex
electron paramagnetic resonance (EPR) spectrum due to multiple low-spin (S = 1/2)
Fe(III) species. Four distinct signals can be assigned to the resting active
state, the active state bound to butyric acid, an oxidized Fe(III)-bis(sulfinic
acid) form, and an oxidized complex with butyric acid. A combination of
comparison with earlier work, development of methods to elicit individual
signals, and design and application of a novel density functional theory method
for reproducing g tensors to unprecedentedly high precision was used to assign
the signals. These species account for the previously reported EPR spectra from
Fe-NHases, including spectra observed upon addition of substrates. Completely new
EPR signals were observed upon addition of inhibitory boronic acids, and the
distinctive g1 features of these signals were replicated in the steady state with
the slow substrate acetonitrile. This latter signal constitutes the first EPR
signal from a catalytic intermediate of NHase and is assigned to a key
intermediate in the proposed catalytic cycle. Earlier, apparently contradictory,
electron nuclear double resonance reports are reconsidered in the context of this
work.
PMID- 28520401
TI - Identification of GalNAc-Conjugated Antisense Oligonucleotide Metabolites Using
an Untargeted and Generic Approach Based on High Resolution Mass Spectrometry.
AB - Antisense oligonucleotides linked by phosphorothioates are an important class of
therapeutics under investigation in various pharmaceutical companies. Antisense
oligonucleotides may be coupled to high-affinity ligands (triantennary N-acetyl
galactosamine = GalNAc) for hepatocyte-specific asialoglycoprotein receptors
(ASGPR) to enhance uptake to hepatocytes and to increase potency. Since
disposition and biotransformation of GalNAc-conjugated oligonucleotides is
different from unconjugated oligonucleotides, appropriate analytical methods are
required to identify main cleavage sites and degradation products of GalNAc
conjugated and unconjugated oligonucleotides in target cells. A highly sensitive
method was developed to identify metabolites of oligonucleotides using capillary
flow liquid chromatography with column switching coupled to a high resolution
Orbitrap Fusion mass spectrometer. Detection of GalNAc-conjugated
oligonucleotides and their metabolites was achieved by combining full scan MS
with two parallel MS2 experiments, one data-dependent scan and an untargeted MS2
experiment (all ion fragmentation) applying high collision energy. In the all ion
fragmentation scan, a diagnostic fragment originating from the phosphorothioate
backbone (O2PS-: m/z 94.936) was formed efficiently upon collisional activation.
Based on this fragment an accurate determination of metabolites of
oligonucleotides was achieved, independent of their sequence or conjugation in an
untargeted but highly selective manner. The method was effectively applied to
investigate uptake and metabolism of GalNAc-conjugated oligonucleotides in
incubations of primary rat hepatocytes; the elucidation of expected and
unexpected degradation products was achieved in subnanomolar range.
PMID- 28520403
TI - Integrated Strategy for Unknown EI-MS Identification Using Quality Control
Calibration Curve, Multivariate Analysis, EI-MS Spectral Database, and Retention
Index Prediction.
AB - Compound identification using unknown electron ionization (EI) mass spectra in
gas chromatography coupled with mass spectrometry (GC-MS) is challenging in
untargeted metabolomics, natural product chemistry, or exposome research. While
the total count of EI-MS records included in publicly or commercially available
databases is over 900 000, efficient use of this huge database has not been
achieved in metabolomics. Therefore, we proposed a "four-step" strategy for the
identification of biologically significant metabolites using an integrated
cheminformatics approach: (i) quality control calibration curve to reduce
background noise, (ii) variable selection by hypothesis testing in principal
component analysis for the efficient selection of target peaks, (iii) searching
the EI-MS spectral database, and (iv) retention index (RI) filtering in
combination with RI predictions. In this study, the new MS-FINDER spectral search
engine was developed and utilized for searching EI-MS databases using mass
spectral similarity with the evaluation of false discovery rate. Moreover, in
silico derivatization software, MetaboloDerivatizer, was developed to calculate
the chemical properties of derivative compounds, and all retention indexes in EI
MS databases were predicted using a simple mathematical model. The strategy was
showcased in the identification of three novel metabolites (butane-1,2,3-triol, 3
deoxyglucosone, and palatinitol) in Chinese medicine Senkyu for quality
assessment, as validated using authentic standard compounds. All tools and
curated public EI-MS databases are freely available in the 'Computational MS
based metabolomics' section of the RIKEN PRIMe Web site (
http://prime.psc.riken.jp ).
PMID- 28520402
TI - Catch and Release: Engineered Allosterically Regulated beta-Roll Peptides Enable
On/Off Biomolecular Recognition.
AB - Alternative scaffolds for biomolecular recognition are being developed to
overcome some of the limitations associated with immunoglobulin domains. The
repeat-in-toxin (RTX) domain is a repeat protein sequence that reversibly adopts
the beta-roll secondary structure motif specifically upon calcium binding. This
conformational change was exploited for controlled biomolecular recognition.
Using ribosome display, an RTX peptide library was selected to identify binders
to a model protein, lysozyme, exclusively in the folded state of the peptide.
Several mutants were identified with low micromolar dissociation constants. After
concatenation of the mutants, a 500-fold increase in the overall affinity for
lysozyme was achieved leading to a peptide with an apparent dissociation constant
of 65 nM. This mutant was immobilized for affinity chromatography experiments,
and the on/off nature of the molecular recognition was demonstrated as the target
is captured from a mixture in the presence of calcium and is released in the
absence of calcium as the RTX peptides lose their beta-roll structure. This work
presents the design of a new stimulus-responsive scaffold that can be used for
environmentally responsive specific molecular recognition and self-assembly.
PMID- 28520404
TI - Enzymatic Reactor with Trypsin Immobilized on Graphene Oxide Modified Polymer
Microspheres To Achieve Automated Proteome Quantification.
AB - Protein digestion and isotope labeling are two critical steps in proteome
quantification. However, the conventional in-solution protocol unavoidably
suffers from disadvantages such as time-consuming, low labeling efficiency, and
tedious off-line manual operation, which might affect the quantification
accuracy, reproducibility, and throughput. To address these problems, we
developed a fully automated proteome quantification platform, in which an
ultraperformance immobilized microreactor (upIMER) with graphene-oxide-modified
polymer microspheres as the matrix was developed, to achieve not only the
simultaneous protein digestion and 18O labeling, but also the online integration
with nano-high-pressure liquid chromatography-electrospray ionization-tandem mass
spectrometry (nanoHPLC-ESI-MS/MS). Compared to the conventional off-line
protocols, such a platform exhibits obviously improved digestion and 18O labeling
efficiency (only 8% peptides with missed cleavage sites, 99% labeling efficiency,
and 2.5 min reaction time), leading to the increased quantification coverage,
accuracy, precision and throughput. All the results demonstrated that our
developed fully automated platform should provide new opportunities to improve
the accuracy, reproducibility, and throughput for proteome quantification.
PMID- 28520405
TI - Morphology-Driven Control of Metabolite Selectivity Using Nanostructure-Initiator
Mass Spectrometry.
AB - Nanostructure-initiator mass spectrometry (NIMS) is a laser desorption/ionization
analysis technique based on the vaporization of a nanostructure-trapped liquid
"initiator" phase. Here we report an intriguing relationship between NIMS surface
morphology and analyte selectivity. Scanning electron microscopy and
spectroscopic ellipsometry were used to characterize the surface morphologies of
a series of NIMS substrates generated by anodic electrochemical etching. Mass
spectrometry imaging was applied to compare NIMS sensitivity of these various
surfaces toward the analysis of diverse analytes. The porosity of NIMS surfaces
was found to increase linearly with etching time where the pore size ranged from
4 to 12 nm with corresponding porosities estimated to be 7-70%. Surface
morphology was found to significantly and selectively alter NIMS sensitivity. The
small molecule (<2k Da) sensitivity was found to increase with increased
porosity, whereas low porosity had the highest sensitivity for the largest
molecules examined. Estimation of molecular sizes showed that this transition
occurs when the pore size is <3* the maximum of molecular dimensions. While the
origins of selectivity are unclear, increased signal from small molecules with
increased surface area is consistent with a surface area restructuring-driven
desorption/ionization process where signal intensity increases with porosity. In
contrast, large molecules show highest signal for the low-porosity and small-pore
size surfaces. We attribute this to strong interactions between the initiator
coated pore structures and large molecules that hinder desorption/ionization by
trapping large molecules. This finding may enable us to design NIMS surfaces with
increased specificity to molecules of interest.
PMID- 28520406
TI - Characterization of 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N
[Methoxy(polyethylene glycerol)-2000] and Its Complex with Doxorubicin Using
Nuclear Magnetic Resonance Spectroscopy and Molecular Dynamics.
AB - Polyethylene glycol (PEG) lipid nanoparticles (LNPs) spontaneously assemble in
water, forming uniformly sized nanoparticles incorporating drugs with prolonged
blood clearance compared to drugs alone. Previously, 1,2-distearoyl-sn-glycero-3
phosphoethanolamine-N-[methoxy(polyethylene glycerol)-2000] (DSPE-PEG2000) and
several drug adducts, including doxorubicin, were analyzed by a combination of
physical and molecular dynamic (MD) studies. In this study, a complete chemical
shift assignment of DSPE-PEG2000 plus or minus doxorubicin was achieved using
nuclear magnetic resonance (NMR), one-dimensional selective nuclear Overhauser
spectroscopy (1D-selNOESY), NOESY, correlation spectroscopy (COSY), total
correlated spectroscopy (TOCSY), heteronuclear single quantum coherence (HSQC),
and HSQC-TOCSY. Chemical shift perturbation, titration, relaxation enhancement,
and NOESY analysis combined with MD reveal detailed structural information at the
atomic level, including the location of doxorubicin in the micelle, its binding
constant, the hydrophilic shell organization, and the mobility of the PEG2000
tail, demonstrating that NMR spectroscopy can characterize drug-DSPE-PEG2000
micelles with molecular weights above 180 kDa. The MD study revealed that an
initial spherical organization led to a more-disorganized oblate structure in an
aqueous environment and agreed with the NMR study in the details of the fine
structure, in which methyl group(s) of the stearic acid in the hydrophobic core
of the micelle are in contact with the phosphate headgroup of the lipid. Although
the molecular size of the LNP drug complex is about 180 kDa, atomic resolution
can be achieved by NMR-based methods that reveal distinct features of the drug
lipid interactions. Because many drugs have unfavorable blood clearance that may
benefit from incorporation into LNPs, a thorough knowledge of their physical and
chemical properties is essential to moving them into a clinical setting. This
study provides an advanced basic approach that can be used to study a wide range
of drug-LNP interactions.
PMID- 28520407
TI - Controlling Configurational Isomerism in Three-Component Colloidal Hybrid
Nanoparticles.
AB - Colloidal hybrid nanoparticles are solution-dispersible constructs that join
together multiple distinct nanoscale materials through direct solid-solid
interfaces. Given their multifunctionality and synergistic properties that emerge
from interfacial coupling, hybrid nanoparticles are of interest for applications
in biomedical imaging, solar energy conversion, heterogeneous catalysis,
nanophotonics, and beyond. High-order hybrid nanoparticles, which incorporate
three or more nanocrystal domains, offer greater tunability and functional
diversity relative to one or two-component nanoparticles. The multiple
heterojunctions within these structures can facilitate complex electromagnetic
coupling as well as cooperative surface processes. Additionally, these materials
can be used as model systems for studying fundamental structure-property
relationships at the nanoscale that arise from particle coupling and interfacial
exchanges. Limiting these advances is the inability to synthesize hybrid
nanoparticles with precise morphologies and geometries. High-order hybrid
nanoparticles can adopt more than one configuration, and each unique arrangement
will have different heterointerfaces and, accordingly, different functions.
Seeded-growth methods are among the most effective methods for producing high
quality hybrid nanoparticles. Engineering complex heterostructures using these
stepwise reactions is in some ways conceptually analogous to the total synthesis
of large organic molecules. However, unlike in molecular synthesis, the rules and
guidelines that underpin the formation of hybrid nanoparticles are less
understood. For example, when a third domain is added to a two-component
heterodimer nanoparticle seed, several distinct types of hybrid nanoparticle
products are possible, but only one is typically observed due to preferred growth
at specific locations. The three-component heterotrimer products that
preferentially form are not necessarily those that have the domain configurations
and heterojunctions required to facilitate a targeted application. Different
arrangements of the three nanoparticles that comprise a heterotrimer lead to
distinct configurational isomers. Accordingly, understanding and controlling
configurational isomerism in nanoparticle heterotrimers is foundational for
engineering high-order hybrid nanostructures with targeted heterointerfaces,
properties, and functionalities. This Account highlights recent insights into the
pathways by which three-component nanoparticle heterotrimers form and how their
configurations can be controlled and modified. In-depth microscopic
investigations into the formation of heterotrimers by growing a third
nanoparticle domain on a two-component heterodimer seed have revealed that in
some cases indiscriminate nucleation first occurs on all exposed surfaces
followed by surface-mediated migration and coalescence to the preferred
interface. This insight helps to rationalize observed site-specific,
chemoselective growth phenomena. Additionally, new approaches for directing
growth in heterotrimer synthesis, such as protection-deprotection schemes
inspired by organic chemistry, are becoming effective tools for constructing
hybrid nanoparticles having nonpreferred domain configurations. Alternatives to
traditional seeded-growth approaches are also emerging, including insertion
reactions driven by saturation-precipitation processes and orthogonal
transformations of preformed hybrid constructs using ion exchange. These and
other recent advances are providing a powerful suite of synthetic tools that are
anticipated to enable function-driven design of high-order hybrid nanoparticles
having targeted properties and applications.
PMID- 28520408
TI - Engineering and Characterization of Bacterial Nanocellulose Films as Low Cost and
Flexible Sensor Material.
AB - Some bacterial strains such as Komagataeibacter xylinus are able to produce
cellulose as an extracellular matrix. In comparison to wood-based cellulose,
bacterial cellulose (BC) holds interesting properties such as biodegradability,
high purity, water-holding capacity, and superior mechanical and structural
properties. Aiming toward improvement in BC production titer and tailored
alterations to the BC film, we engineered K. xylinus to overexpress partial and
complete bacterial cellulose synthase operon that encodes activities for BC
production. The changes in cell growth, end metabolite, and BC production titers
from the engineered strains were compared with the wild-type K. xylinus. Although
there were no significant differences between the growth of wild-type and
engineered strains, the engineered K. xylinus strains demonstrated faster BC
production, generating 2-4-fold higher production titer (the highest observed
titer was obtained with K. xylinus-bcsABCD strain producing 4.3 +/- 0.46 g/L BC
in 4 days). The mechanical and structural characteristics of cellulose produced
from the wild-type and engineered K. xylinus strains were analyzed with a stylus
profilometer, in-house built tensile strength measurement system, a scanning
electron microscope, and an X-ray diffractometer. Results from the profilometer
indicated that the engineered K. xylinus strains produced thicker BC films (wild
type, 5.1 MUm, and engineered K. xylinus strains, 6.2-10.2 MUm). Scanning
electron microscope revealed no principal differences in the structure of the
different type BC films. The crystallinity index of all films was high (from 88.6
to 97.5%). All BC films showed significant piezoelectric response (5.0-20 pC/N),
indicating BC as a promising sensor material.
PMID- 28520409
TI - FeCo-Anchored Reduced Graphene Oxide Framework-Based Soft Composites Containing
Carbon Nanotubes as Highly Efficient Microwave Absorbers with Excellent Heat
Dissipation Ability.
AB - Conducting polymer composites containing ferromagnetic grafted-graphene
derivatives are already appreciated for their lightweight, flexibility, and cost
effectiveness in terms of microwave absorption. To further leverage the said
properties of this wonder material, we propose a highly efficient replacement by
blending conducting multiwall carbon nanotube (MWCNT) and FeCo anchored covalent
cross-linked reduced graphene oxide (rGO) with poly(vinylidene fluoride) (PVDF).
Interconnected conducting network of MWCNTs introduces higher electrical
conductivity in the blend which is essential for microwave absorption. FeCo
anchored porous interconnected rGO framework was designed via solvent-mediated in
situ coreduction in the presence of Fe(II) and Co(II) precursors. Resulting cross
linked-rGO/FeCo displays fascinating coexistence of ferromagnetism and conducting
dielectric behavior, while largely preserving the robust 3D porous interconnected
structure. Coupled with conducting MWCNTs, diamine cross-linked rGO/FeCo in a
soft polymer matrix yields remarkably high total shielding effectiveness (SET) of
-41.2 dB at 12 GHz, for a meager 10 wt % filler content. In addition, the
composite materials display efficient heat dissipation abilities in conjunction
with the trend in their thermal conductivities. This new-age microwave-absorbing
material, powered by multifunctionality and tunable magnetodielectric properties,
henceforth offers an amendable, cost-effective replacement to the existing
solutions.
PMID- 28520410
TI - Proteolytically Stable Cyclic Decapeptide for Breast Cancer Cell Targeting.
AB - Starting with a previously reported linear breast cancer targeting decapeptide
WxEAAYQkFL, here we report the synthesis of a novel cyclic peptide analogue
cyclic WXEAAYQkFL. The N- to C-terminus amide cyclized peptide with one d-amino
acid (k) displayed higher uptake by breast cancer cells, with minimal uptake by
the noncancerous cells compared to the linear peptide with two d-amino acids (x
and k), and was stable toward proteolytic degradation. When immobilized on gold
microcantilever surface, the cyclic peptide was able to capture breast cancer
cells specifically and sense samples with >=25 cancer cells/mL. Animal studies
using mice carrying orthotopic breast MDA-MB-231 tumors showed that the cyclic
peptide preferentially accumulates in tumor (2 h after injection) and is rapidly
cleared from all other organs except kidneys and liver. The study highlights the
discovery of a novel proteolytically stable cyclic peptide that can be used for
targeted drug delivery or for enumerating circulating breast tumor cells.
PMID- 28520411
TI - Alignment-Based Prediction of Sites of Metabolism.
AB - Prediction of metabolically labile atom positions in a molecule (sites of
metabolism) is a key component of the simulation of xenobiotic metabolism as a
whole, providing crucial information for the development of safe and effective
drugs. In 2008, an exploratory study was published in which sites of metabolism
were derived based on molecular shape- and chemical feature-based alignment to a
molecule whose site of metabolism (SoM) had been determined by experiments. We
present a detailed analysis of the breadth of applicability of alignment-based
SoM prediction, including transfer of the approach from a structure- to ligand
based method and extension of the applicability of the models from cytochrome
P450 2C9 to all cytochrome P450 isozymes involved in drug metabolism. We evaluate
the effect of molecular similarity of the query and reference molecules on the
ability of this approach to accurately predict SoMs. In addition, we combine the
alignment-based method with a leading chemical reactivity model to take
reactivity into account. The combined model yielded superior performance in
comparison to the alignment-based approach and the reactivity models with an
average area under the receiver operating characteristic curve of 0.85 in cross
validation experiments. In particular, early enrichment was improved, as
evidenced by higher BEDROC scores (mean BEDROC = 0.59 for alpha = 20.0, mean
BEDROC = 0.73 for alpha = 80.5).
PMID- 28520413
TI - Temporal Characteristics of Brown Carbon over the Central Indo-Gangetic Plain.
AB - Recent global models estimate that light absorption by brown carbon (BrC) in
several regions of the world is ~30-70% of that due to black carbon (BC). It is,
therefore, important to understand its sources and characteristics on temporal
and spatial scales. In this study, we conducted semicontinuous measurements of
water-soluble organic carbon (WSOC) and BrC using particle-into-liquid sampler
coupled with a liquid waveguide capillary cell and total organic carbon analyzer
(PILS-LWCC-TOC) over Kanpur (26.5 degrees N, 80.3 degrees E, 142 m amsl) during a
winter season (December 2015 to February 2016). In addition, mass concentrations
of organic and inorganic aerosol and BC were also measured. Diurnal variability
in the absorption coefficient of BrC at 365 nm (babs_365) showed higher values
(35 +/- 21 Mm-1) during late evening to early morning hours and was attributed to
primary emissions from biomass burning (BB) and fossil fuel burning (FFB). The
babs_365 reduced by more than 80% as the day progressed, which was ascribed to
photo bleaching/volatilization of BrC and/or due to rising boundary layer height.
Further, diurnal variability in the ratios of babs_405/babs_365 and
babs_420/babs_365 suggests that the BrC composition was not uniform throughout a
day. WSOC exhibited a strong correlation with babs_365 (slope = 1.22 +/- 0.007,
r2 = 0.70, n = 13 265, intercept = -0.69 +/- 0.17), suggesting the presence of a
significant but variable fraction of chromophores. Mass absorption efficiency
(MAE) values of WSOC ranged from 0.003 to 5.26 m2 g-1 (1.16 +/- 0.60) during the
study period. Moderate correlation (r2 = 0.50, slope = 1.58 +/- 0.019, n = 6471)
of babs_365 was observed with the semivolatile oxygenated organic aerosols (SV
OOA) fraction of BB resolved from positive matrix factorization (PMF) analysis of
organic mass spectral data obtained from a high-resolution time-of-flight aerosol
mass spectrometer (HR-ToF-AMS). The low-volatility OOA (LV-OOA) fraction of BB
had a similar correlation to babs_365 (r2 = 0.54, slope = 0.38 +/- 0.004, n =
6471) but appears to have a smaller contribution to the absorption.
PMID- 28520414
TI - Structural and Magnetic Transitions in CaCo3V4O12 Perovskite at Extreme
Conditions.
AB - We investigated the structural, vibrational, magnetic, and electronic properties
of the recently synthesized CaCo3V4O12 double perovskite with the high-spin (HS)
Co2+ ions in a square-planar oxygen coordination at extreme conditions of high
pressures and low temperatures. The single-crystal X-ray diffraction and Raman
spectroscopy studies up to 60 GPa showed a conservation of its cubic crystal
structure but indicated a crossover near 30 GPa. Above 30 GPa, we observed both
an abnormally high "compressibility" of the Co-O bonds in the square-planar
oxygen coordination and a huge anisotropic displacement of HS-Co2+ ions in the
direction perpendicular to the oxygen planes. Although this effect is reminiscent
of a continuous HS -> LS transformation of the Co2+ ions, it did not result in
the anticipated shrinkage of the cell volume because of a certain "stiffing" of
the bonds of the Ca and V cations. We verified that the oxidation states of all
the cations did not change across this crossover, and hence, no charge-transfer
effects were involved. Consequently, we proposed that CaCo3V4O12 could undergo a
phase transition at which the large HS-Co2+ ions were pushed out of the oxygen
planes because of lattice compression. The antiferromagnetic transition in
CaCo3V4O12 at 100 K was investigated by neutron powder diffraction at ambient
pressure. We established that the magnetic moments of the Co2+ ions were aligned
along one of the cubic axes, and the magnetic structure had a 2-fold periodicity
along this axis, compared to the crystallographic one.
PMID- 28520412
TI - Identification of the Ferredoxin-Binding Site of a Ferredoxin-Dependent
Cyanobacterial Nitrate Reductase.
AB - An in silico model for the 1:1 ferredoxin (Fd)/nitrate reductase (NR) complex,
using the known structure of Synechocystis sp. PCC 6803 Fd and the in silico
model of Synechococcus sp. PCC 7942 NR, is used to map the interaction sites that
define the interface between Fd and NR. To test the electrostatic interactions
predicted by the model complex, five positively charged NR amino acids (Arg43,
Arg46, Arg197, Lys201, and Lys614) and a negatively charged amino acid (Glu219)
were altered using site-directed mutagenesis and characterized by activity
measurements, metal analysis, and electron paramagnetic resonance (EPR) studies.
All of the charge replacement variants retained wild-type levels of activity with
reduced methyl viologen (MV), but a significant decrease in activity was observed
for the R43Q, R46Q, K201Q, and K614Q variants when reduced Fd served as the
electron donor. EPR analysis as well as the Fe and Mo analyses showed that loss
of activity observed with these variants was not the consequence of perturbation
of the Mo center or [4Fe-4S] cluster. Therefore, the loss of the Fd-linked
specific activity observed with these variants can be explained only by invoking
a role for Arg43, Arg46, Lys201, and Lys614 in Fd binding. The R43Q, R46Q, K201Q,
and K614Q NR variants also showed a decreased binding affinity for Fd, compared
to that of wild-type NR, supporting a key role of these four positively charged
residues in the productive binding of Fd.
PMID- 28520415
TI - Design and Synthesis of Soluble and Cell-Permeable PI3Kdelta Inhibitors for Long
Acting Inhaled Administration.
AB - PI3Kdelta is a lipid kinase that is believed to be important in the migration and
activation of cells of the immune system. Inhibition is hypothesized to provide a
powerful yet selective immunomodulatory effect that may be beneficial for the
treatment of conditions such as asthma or rheumatoid arthritis. In this work, we
describe the identification of inhibitors based on a thiazolopyridone core
structure and their subsequent optimization for inhalation. The initially
identified compound (13) had good potency and isoform selectivity but was not
suitable for inhalation. Addition of basic substituents to a region of the
molecule pointing to solvent was tolerated (enzyme inhibition pIC50 > 9), and by
careful manipulation of the pKa and lipophilicity, we were able to discover
compounds (20b, 20f) with good lung retention and cell potency that could be
taken forward to in vivo studies where significant target engagement could be
demonstrated.
PMID- 28520416
TI - Experimental and Theoretical Evaluation of the Stability of True MOF Polymorphs
Explains Their Mechanochemical Interconversions.
AB - We provide the first combined experimental and theoretical evaluation of how
differences in ligand structure and framework topology affect the relative
stabilities of isocompositional (i.e., true polymorph) metal-organic frameworks
(MOFs). We used solution calorimetry and periodic DFT calculations to analyze the
thermodynamics of two families of topologically distinct polymorphs of zinc
zeolitic imidazolate frameworks (ZIFs) based on 2-methyl- and 2-ethylimidazolate
linkers, demonstrating a correlation between measured thermodynamic stability and
density, and a pronounced effect of the ligand substituent on their stability.
The results show that mechanochemical syntheses and transformations of ZIFs are
consistent with Ostwald's rule of stages and proceed toward thermodynamically
increasingly stable, more dense phases.
PMID- 28520417
TI - Correction to Evaluating the Role of Multidrug Resistance Protein 3 (MDR3)
Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals.
PMID- 28520419
TI - Single Particle Tracking: From Theory to Biophysical Applications.
AB - After three decades of developments, single particle tracking (SPT) has become a
powerful tool to interrogate dynamics in a range of materials including live
cells and novel catalytic supports because of its ability to reveal dynamics in
the structure-function relationships underlying the heterogeneous nature of such
systems. In this review, we summarize the algorithms behind, and practical
applications of, SPT. We first cover the theoretical background including
particle identification, localization, and trajectory reconstruction. General
instrumentation and recent developments to achieve two- and three-dimensional
subdiffraction localization and SPT are discussed. We then highlight some
applications of SPT to study various biological and synthetic materials systems.
Finally, we provide our perspective regarding several directions for future
advancements in the theory and application of SPT.
PMID- 28520418
TI - Polycyclic Furanobutenolide-Derived Cembranoid and Norcembranoid Natural
Products: Biosynthetic Connections and Synthetic Efforts.
AB - The polycyclic furanobutenolide-derived cembranoid and norcembranoid natural
products are a family of congested, stereochemically complex, and extensively
oxygenated polycyclic diterpenes and norditerpenes. Although the elegant
architectures and biological activity profiles of these natural products have
captured the attention of chemists since the isolation of the first members of
the family in the 1990s, the de novo synthesis of only a single polycyclic
furanobutenolide-derived cembranoid and norcembranoid has been accomplished. This
article begins with a brief discussion of the proposed biosyntheses and
biosynthetic connections among the polycyclic furanobutenolide-derived
cembranoids and norcembranoids and then provides a comprehensive review of the
synthetic efforts toward each member of the natural product family, including
biomimetic, semisynthetic, and de novo synthetic strategies. This body of
knowledge has been gathered to provide insight into the reactivity and
constraints of these compact and highly oxygenated polycyclic structures, as well
as to offer guidance for future synthetic endeavors.
PMID- 28520420
TI - Local Descriptors of Dynamic and Nondynamic Correlation.
AB - Quantitatively accurate electronic structure calculations rely on the proper
description of electron correlation. A judicious choice of the approximate
quantum chemistry method depends upon the importance of dynamic and nondynamic
correlation, which is usually assesed by scalar measures. Existing measures of
electron correlation do not consider separately the regions of the Cartesian
space where dynamic or nondynamic correlation are most important. We introduce
real-space descriptors of dynamic and nondynamic electron correlation that admit
orbital decomposition. Integration of the local descriptors yields global numbers
that can be used to quantify dynamic and nondynamic correlation. Illustrative
examples over different chemical systems with varying electron correlation
regimes are used to demonstrate the capabilities of the local descriptors. Since
the expressions only require orbitals and occupation numbers, they can be readily
applied in the context of local correlation methods, hybrid methods, density
matrix functional theory, and fractional-occupancy density functional theory.
PMID- 28520421
TI - Examining the Feasibility of Using Free Energy Perturbation (FEP+) in Predicting
Protein Stability.
AB - The importance of engineering protein stability is well-known and has the
potential to impact many fields ranging from pharmaceuticals to food sciences.
Engineering proteins can be both a time-consuming and expensive experimental
process. The use of computation is a potential solution to mitigating some of the
time and expenses required to engineer a protein. This process has been
previously hindered by inaccurate force fields or energy equations and slow
computational processors; however, improved software and hardware have made this
goal much more attainable. Here we find that Schrodinger's new FEP+, although
still imperfect, proves more successful in predicting protein stability than
other simpler methods of investigation. This increased accuracy comes at a cost
of computational time and resources when compared to simpler methods. This work
adds to the initial testing of FEP+ by offering options for more accurately
predicting protein stability in an efficient manner.
PMID- 28520423
TI - Interstitial Bismuth Atoms in Icosahedral Rhodium Cages: Syntheses,
Characterizations, and Molecular Structures of the [Bi@Rh12(CO)27]3-,
[(Bi@Rh12(CO)26)2Bi]5-, [Bi@Rh14(CO)27Bi2]3-, and [Bi@Rh17(CO)33Bi2]4- Carbonyl
Clusters.
AB - The reaction of [Rh7(CO)16]3- with BiCl3 under N2 and at room temperature results
in the formation of the new heterometallic [Bi@Rh12(CO)27]3- cluster in high
yields. Further controlled addition of BiCl3 leads first to the formation of the
dimeric [(Bi@Rh12(CO)26)2Bi]5- and the closo-[Bi@Rh14(CO)27Bi2]3- species in low
yields, and finally, to the [Bi@Rh17(CO)33Bi2]4- cluster. All clusters were
spectroscopically characterized by IR and electrospray ionization mass
spectrometry, and their molecular structures were fully determined by X-ray
diffraction studies. Notably, they represent the first examples of Bi atoms
interstitially lodged in metallic cages that, in this specific case, are all
based on an icosahedral geometry. Moreover, [Bi@Rh14(CO)27Bi2]3- forms an
exceptional network of infinite zigzag chains in the solid state, thanks to
intermolecular Bi-Bi distances.
PMID- 28520422
TI - Global Land Use Regression Model for Nitrogen Dioxide Air Pollution.
AB - Nitrogen dioxide is a common air pollutant with growing evidence of health
impacts independent of other common pollutants such as ozone and particulate
matter. However, the worldwide distribution of NO2 exposure and associated
impacts on health is still largely uncertain. To advance global exposure
estimates we created a global nitrogen dioxide (NO2) land use regression model
for 2011 using annual measurements from 5,220 air monitors in 58 countries. The
model captured 54% of global NO2 variation, with a mean absolute error of 3.7
ppb. Regional performance varied from R2 = 0.42 (Africa) to 0.67 (South America).
Repeated 10% cross-validation using bootstrap sampling (n = 10,000) demonstrated
a robust performance with respect to air monitor sampling in North America,
Europe, and Asia (adjusted R2 within 2%) but not for Africa and Oceania (adjusted
R2 within 11%) where NO2 monitoring data are sparse. The final model included 10
variables that captured both between and within-city spatial gradients in NO2
concentrations. Variable contributions differed between continental regions, but
major roads within 100 m and satellite-derived NO2 were consistently the
strongest predictors. The resulting model can be used for global risk assessments
and health studies, particularly in countries without existing NO2 monitoring
data or models.
PMID- 28520424
TI - Insights on the Reactivity of Terminal Phosphanido Metal Complexes toward
Activated Alkynes from Theoretical Computations.
AB - Herein we present a theoretical study on the reaction of [Re(PPh2) (CO)3(phen)]
(phen = 1,10-phenanthroline) and [Re(PPh2) (CO)3(bipy)] (bipy = 2,2'-bipyridine)
toward methyl propiolate. In agreement with experimental results for the phen
ligand, the coupling of the substituted acetylenic carbon with the nonsubstituted
ortho carbon of the phen ligand is the preferred route from both kinetic and
thermodynamic viewpoints with a Gibbs energy barrier of 18.8 kcal/mol and an
exoergicity of 11.1 kcal/mol. There are other two routes, the insertion of the
acetylenic fragment into the P-Re bond and the coupling between the substituted
acetylenic carbon and a carbonyl ligand in cis disposition, which are kinetically
less favorable than the preferred route (by 2.8 and 1.9 kcal/mol, respectively).
Compared with phen, the bipy ligand shows less electrophilic character and also
less pi electron delocalization due to the absence of the fused ring between the
two pyridine rings. As a consequence, the route involving the coupling with a
carbonyl ligand starts to be kinetically competitive, whereas the product of the
attack to bipy is still the most stable and would be the one mainly obtained
after spending enough time to reach thermal equilibrium.
PMID- 28520425
TI - Furan and Lactam Jadomycin Biosynthetic Congeners Isolated from Streptomyces
venezuelae ISP5230 Cultured with Nepsilon-Trifluoroacetyl-l-lysine.
AB - Angucycline antibiotics are composed of a classical four-ring angularly linked
polyaromatic backbone. Differential cyclization chemistry of the A- and B-rings
in jadomycin biosynthesis led to the discovery of two new furan analogues, while
oxidation led to a ring-opened form of the jadomycin Nepsilon-trifluoroacetyl-l
lysine (TFAL) congener. The compounds were isolated from Streptomyces venezuelae
ISP5230 cultures grown with TFAL. Biosynthetic incorporation using d-[1-13C]
glucose in cultures enabled the unambiguous assignment of the aldehyde, alcohol,
and amide functionalities present in these new congeners through NMR
spectroscopy. Tandem mass spectrometry analysis of cultures grown with 15Nalpha-
or 15Nepsilon-lysine demonstrated the incorporation of Nalpha exclusively into
the angucycline backbone, contrasting results with ornithine [J. Am. Chem. Soc.
2015, 137, 3271]. Compounds were evaluated against antimicrobial and cancer cell
panels and found to possess good activity against Gram-positive bacteria.
PMID- 28520427
TI - Kinetic Monte Carlo Modeling of Charge Carriers in Organic Electronic Devices:
Suppression of the Self-Interaction Error.
AB - Kinetic Monte Carlo (KMC) simulations have emerged as an important tool to help
improve the efficiency of organic electronic devices by providing a better
understanding of their device physics. In the KMC simulation of an organic
device, the reliability of the results depends critically on the accuracy of the
chosen charge-transfer rates, which are themselves strongly influenced by the
site-energy differences. These site-energy differences include components coming
from the electrostatic forces present in the system, which are often evaluated
through electric potentials described by the Poisson equation. Here we show that
the charge-carrier self-interaction errors that appear when evaluating the site
energy differences can lead to unreliable simulation results. To eliminate these
errors, we propose two approaches that are also found to reduce the impact of
finite-size effects. As a consequence, reliable results can be obtained at
reduced computational costs. The proposed methodologies can be extended to other
device simulation techniques as well.
PMID- 28520426
TI - Reconsideration of the Rheology of Silica Filled Natural Rubber Compounds.
AB - There is substantial progress along with giant debate in reinforcement mechanisms
in relation to structured filler network and heterogeneously retarded polymer
dynamics, while the dissipation behaviors have never been clarified for
nanoparticle filled polymers. Herein dynamic rheological behaviors of silica
filled natural rubber were investigated. Master curves of linear rheology in the
hydrodynamic regime and those of the nonlinear Payne effect at a predetermined
frequency were created, disclosing a leading role of dynamically retarded bulk
rubbery phase to the hydrodynamic regime and a leading role of molecular
disentanglement in the bulk phase to the Payne effect. The methodology is able to
account for both reinforcement and dissipation of the compounds as a function of
filler content. Furthermore, a frequency-dependent hydrodynamic to non
hydrodynamic transition is revealed, revealing the importance of the relaxation
of chains in the bulk phase to both reinforcement and dissipation of the
compounds. It is suggested that the dynamics of the bulk phase play a critical
role for the rheology in the hydrodynamic regime while the fractal filler
aggregates become dominative only in the terminal non-hydrodynamic regime where
the bulk phase relaxes sufficiently.
PMID- 28520429
TI - Raman Radial Mode Revealed from Curved Graphene.
AB - One of the unsolved fundamental issues of graphene is establishing an appropriate
way to discern layers of graphene structures. We report a simple methodology to
analyze graphene structures using Raman signals in the range of ~100 to ~500 cm-1
comprising clear 118 or 175 cm-1 peaks. We demonstrate that the low-energy
signals on Raman spectra of plasma-seeded grown graphene sheets originated from
nanocurvature (c) of mono- (175 and 325-500 cm-1 signals) (c ~ 1 nm) and bilayer
(118 cm-1 peak) (c ~ 2 nm) graphene with Raman simulations, based on Raman radial
mode (RM) Eigen vectors. Our RM model provides a standard way of identifying and
evaluating graphene structures.
PMID- 28520428
TI - Cyclic Diarylheptanoids from Corylus avellana Green Leafy Covers: Determination
of Their Absolute Configurations and Evaluation of Their Antioxidant and
Antimicrobial Activities.
AB - The methanol extract of the leafy covers of Corylus avellana, source of the
Italian PGI (protected geographical indication) product "Nocciola di Giffoni",
afforded two new cyclic diarylheptanoids, giffonins T and U (2 and 3), along with
two known cyclic diarylheptanoids, a quinic acid, flavonoid-, and citric acid
derivatives. The structures of giffonins T and U were determined as highly
hydroxylated cyclic diarylheptanoids by 1D and 2D NMR experiments. Their relative
configurations were assigned by a combined quantum mechanical/NMR approach,
comparing the experimental 13C/1H NMR chemical shift data and the related
predicted values. The absolute configurations of carpinontriol B (1) and
giffonins T and U (2 and 3) were assigned by comparison of their experimental
electronic circular dichroism curves with the TDDFT-predicted curves. The ability
of the compounds to inhibit the lipid peroxidation induced by H2O2 and H2O2/Fe2+
was determined by measuring the concentration of thiobarbituric acid reactive
substances. Furthermore, the antimicrobial activity of the methanol extract of
leafy covers of C. avellana and of the isolated compounds against the Gram
positive strains Bacillus cereus and Staphylococcus aureus and the Gram-negative
strains Escherichia coli and Pseudomonas aeruginosa was evaluated. Carpinontriol
B (1) and giffonin U (3) at 40 MUg/disk caused the formation of zones of
inhibition.
PMID- 28520431
TI - Anomalous Behavior of Ultra-Low-Amplitude Capillary Waves. A Glimpse of the
Viscoelastic Properties of Interfacial Water?
AB - We investigate, both theoretically and by a differential interferometric
technique, the behavior of large-wavelength capillary waves (of the order of 10-4
m) selectively excited at the surface of drops and bubbles with typical
eigenfrequencies of the order of 102 Hz. The resonance peaks of gas bubbles or
hydrocarbon drops in water (radius less than 1 mm) highlight anomalously small
dissipation in the region of ultralow (sub-nanometric) oscillation amplitudes,
reaching a plateau at higher amplitudes. This is in sharp contrast to the usual
oscillating systems, where an anomalous behavior holds at large amplitudes alone.
Dissipation is strongly dependent on the excited vibrational modes and, in spite
of remarkable numerical differences, water-vapor and water-hydrocarbon interfaces
exhibit the same overall trend. A phenomenological model was developed, based on
the assumption that water possesses a threshold viscoelasticity, above which it
behaves like a regular viscous fluid. The well-known Deborah number was then
estimated within the anomalous region and found to lie in the range of
viscoelastic fluids. In agreement with previous studies of nanohydrodynamics
(e.g., atomic force microscopy measurements with sub-nanometric tip motions), the
present one lends support to the idea that every self-aggregating fluid exhibits
yield stress behavior, including classical Newtonian fluids like water. The
essential requirement is that the applied perturbation lie below a critical
threshold, above which viscous behavior is recovered. Our differential
interferometric technique seems particularly suitable for this type of studies,
as it allows measurement of long-wavelength capillary waves with sub-nanometric
resolution on the oscillation amplitudes.
PMID- 28520430
TI - Fluorescence Dynamics of a FRET Probe Designed for Crowding Studies.
AB - Living cells are crowded with macromolecules and organelles. As a result, there
is an urgent need for molecular sensors for quantitative, site-specific
assessment of the macromolecular crowding effects on a myriad of biochemical
processes toward quantitative cell biology and biophysics. Here we investigate
the excited-state dynamics and translational diffusion of a novel FRET sensor
(mCerulean-linker-mCitrine) in a buffer (PBS, pH 7.4) at room temperature.
Complementary experiments were carried out on free CFP, YFP, and the cleaved FRET
probe as controls. The wavelength-dependent fluorescence lifetime measurements of
the donor and acceptor in the FRET probe, using the time-correlated single-photon
counting technique, indicate an energy transfer efficiency of 6.8 +/- 0.9% in
PBS, with distinct excited-state dynamics from the recombinant CFP and YFP. The
estimated mCerulean-mCitrine distance in this FRET probe is 7.7 +/- 0.2 nm. The
energy transfer efficiency increases (11.5 +/- 0.9%) as the concentration of
Ficoll-70 increases over the range of 0-300 g/L with an estimated mCerulean
mCitrine distance of 6.1 +/- 0.2 nm. Complementary time-resolved anisotropy
measurements suggest that the rotational diffusion of hetero-FRET in PBS is
sensitive to the energy transfer from the donor to the acceptor. The results also
suggest that the linker, -(GSG)6A(EAAAK)6A(GSG)6A(EAAAK)6A(GSG)6-, is rather
flexible, and the observed rotational dynamics is likely to be due to a segmental
mobility of the FRET pairs rather than an overall tumbling motion of a rigid
probe. Comparative studies on a new construct of a FRET probe with a shorter,
more flexible linker, mCerulean-(GSG)18-mCitrine, reveal enhanced energy transfer
efficiency. On the millisecond time scale, fluorescence fluctuation analyses of
the acceptor (excited at 488 nm) provide a means to examine the translational
diffusion coefficient of the FRET probe. The results also suggest that the linker
is flexible in this FRET probe, and the observed diffusion coefficient is faster
than predicted as compared to the cleaved FRET probe. Our results serve as a
point of reference for this FRET probe in a buffer toward its full potential as a
sensor for macromolecular crowding in living cells and tissues.
PMID- 28520432
TI - Insights into Glycol Ether-Alkanol Mixtures from a Combined Experimental and
Theoretical Approach.
AB - The binary liquid mixtures of glycol ethers (glymes) + 1-alkanol were
characterized from the microscopic and macroscopic viewpoints through a combined
experimental and theoretical study. Structuring, dynamics, and intermolecular
forces were determined using density functional theory and classical molecular
dynamics methods. The macroscopic behavior was studied though the measurement of
relevant physicochemical properties and Raman IR studies. The changes in
intermolecular forces with mixture composition, temperature, and the effects from
the types of glymes as well as 1-alkanols were considered. Hydrogen bonding in
the mixed fluids, its changes upon mixing, and mixture composition showed a large
effect on fluids' structure and determined most of the fluids' properties
together with the presence of hydrophobic domains from long 1-alkanols.
PMID- 28520433
TI - Toward a Rigorous Definition of a Strength of Any Interaction Between Bader's
Atomic Basins.
AB - Strength of interaction between Bader's atomic basins, enclosed by zero-flux
surfaces of electron distribution, was proposed to be a measure of elastic
deformation of an interaction. The set containing 53 atomic aggregate and
covering all range of interaction strength (from van der Waals interactions to
triple covalent bonds) was calculated by DFT and perturbation theory methods.
Further analysis was performed to seek correlations between various local
quantities based on electron density and effective force constants of stretching
diatomic vibrations. The linear trend between effective force constants and the
potential energy density at the (3, -1) critical point of electron distribution
was found. This correlation was improved by the integration of the potential
energy density over an interbasin zero-flux surface of electron density. Simple
mechanical explanation of established trends is presented. The correlations can
be further used to at least semiquantitatively compare any pair of interactions
between Bader's atomic basins.
PMID- 28520434
TI - The Nature of Electron Mobility in Hybrid Perovskite CH3NH3PbI3.
AB - CH3NH3PbI3 is one of the most promising candidates for cheap and high-efficiency
solar cells. One of its unique features is the long carrier diffusion length
(>100 MUm), but its carrier mobility is rather modest. The nature of the mobility
is unclear. Here, using nonadiabatic wave function dynamics simulations, we show
that the random rotations of the CH3NH3 cations play an important role in the
carrier mobility. Our previous work showed that the electron and hole wave
functions were localized and spatially separated due to the random orientations
of the CH3NH3 cations in the tetragonal phase. We find that the localized
carriers are able to conduct random walks due to the electrostatic potential
fluctuation caused by the CH3NH3 random rotations. The calculated electron
mobilities are in the experimentally measured range. We thus conclude that the
carrier mobility of CH3NH3PbI3 is likely driven by the dynamic disorder that
causes the fluctuation of the electrostatic potential.
PMID- 28520435
TI - Modulation of Electron-Phonon Coupling in One-Dimensionally Nanorippled Graphene
on a Macrofacet of 6H-SiC.
AB - Local electron-phonon coupling of a one-dimensionally nanorippled graphene is
studied on a SiC(0001) vicinal substrate. We have characterized local atomic and
electronic structures of a periodically nanorippled graphene (3.4 nm period)
prepared on a macrofacet of the 6H-SiC crystal using scanning tunneling
microscopy/spectroscopy (STM/STS) and angle-resolved photoelectron spectroscopy
(ARPES). The rippled graphene on the macrofacets distributes homogeneously over
the 6H-SiC substrate in a millimeter scale, and thus replica bands are detected
by the macroscopic ARPES. The STM/STS results indicate the strength of electron
phonon coupling to the out-of-plane phonon at the K points of graphene is
periodically modified in accordance with the ripple structure. We propose an
interface carbon nanostructure with graphene nanoribbons between the surface
rippled graphene and the substrate SiC that periodically modifies the electron
phonon coupling in the surface graphene.
PMID- 28520436
TI - Controlling Structure and Function of Polymeric Drug Delivery Nanoparticles Using
Microfluidics.
AB - We demonstrate control of multiscale structure and drug delivery function for
paclitaxel (PAX)-loaded polycaprolactone-block-poly(ethylene oxide) (PCL-b-PEO)
polymeric nanoparticles (PNPs) via synthesis and flow-directed shear processing
in a two-phase gas-liquid microfluidic reactor. This strategy takes a page from
the engineering of commodity plastics, where processing rather than polymer
chemistry provides an experimental handle on properties and function. PNPs formed
from copolymers with three different PCL block lengths show sizes, morphologies,
and loading efficiencies that depend on both the PCL block length and the
microfluidic flow rate. By varying flow rate and comparing with a conventional
bulk method of PNP preparation, we show that flow-variable shear processing
provides control of PNP sizes and morphologies and enables slower PAX release
times (up to 2 weeks) compared to bulk-prepared PNPs. Antiproliferative effects
against cultured MCF-7 breast cancer cells were greatest for PNPs formed at an
intermediate flow rate, corresponding to small and low-polydispersity spheres
formed uniquely at this flow condition. Formation and flow-directed nanoscale
shear processing in gas-liquid microfluidic reactors provides a manufacturing
platform for drug delivery PNPs that could enable more effective and selective
nanomedicines through multiscale structural control.
PMID- 28520437
TI - Synthesis of Fused Polycyclic 1,4-Benzodiazepines via Metal-Free Cascade [5 +
2]/[2 + 2] Cycloadditions.
AB - A metal-catalyst-free, mild, and efficient synthetic protocol for polycyclic 1,4
benzodiazepines via cascade [5 + 2]/[2 + 2] cycloadditions between pyridinium
zwitterions and arynes is reported. Mechanistic experiments revealed that
pyridinium zwitterions act as 1,5-dipoles in [5 + 2] cycloadditions with arynes
for the construction of 1,4-benzodiazepines, which further undergo [2 + 2]
cycloaddition resulting in the one-pot formation of one C-N bond and three C-C
bonds.
PMID- 28520438
TI - Noncovalent Surface Modification of Cellulose Nanopapers by Adsorption of
Polymers from Aprotic Solvents.
AB - Basic adsorption of hydrophobic polymers from aprotic solvents was introduced as
a platform technology to modify exclusively the surfaces of cellulose nanopapers.
Dynamic vapor sorption demonstrated that the water vapor uptake ability of the
nanopapers remained unperturbed, despite strong repellency to liquid water caused
by the adsorbed hydrophobic polymer on the surface. This was enabled by the fact
that the aprotic solvents used for adsorption did not swell the nanopaper unlike
water that is generally applied as the adsorption medium in such systems. As case
examples, the adsorptions of polystyrene (PS) and poly(trifluoroethylene) (PF3E)
were followed by X-ray photoelectron spectroscopy and water contact angle
measurements, backed up with morphological analysis by atomic force microscopy.
The resulting nanopapers are useful in applications like moisture buffers where
repellence to liquid water and ability for moisture sorption are desired
qualities.
PMID- 28520439
TI - Cobalt(III)-Catalyzed Oxadiazole-Directed C-H Activation for the Synthesis of 1
Aminoisoquinolines.
AB - Aromatic heterocycles have been identified as effective directing groups (DGs) in
C-H functionalization but can be retained as undesired bulky substituents in the
final products. Herein, we report a Co(III)-catalyzed 1-aminoisoquinoline
synthesis strategy based on oxadiazole-directed aromatic C-H coupling with
alkynes and a subsequent redox-neutral C-N cyclization reaction. This labile N-O
bond-based protocol has allowed the toleration of a broad range of functional
groups.
PMID- 28520440
TI - Synthesis of 3-Benzo[b]thienyl 3-Thienyl Ether via an Addition-Elimination
Reaction and Its Transformation to an Oxygen-Fused Dithiophene Skeleton:
Synthesis and Properties of Benzodithienofuran and Its pi-Extended Derivatives.
AB - The synthesis of 3-benzo[b]thienyl 3-thienyl ether and its dehydrogenative
cyclization leading to benzodithienofuran (BDTF; [1]benzothieno[3,2-b]thieno[2,3
d]furan) are described for the first time. Further transformation of BDTF to more
pi-extended BDTF derivatives and their fundamental physical properties are also
studied.
PMID- 28520441
TI - Total Syntheses of Arcyriaflavin A and Calothrixin B Using 2,2'-Bisindole-3
acetic Acid Derivative as a Common Intermediate.
AB - A new protocol for the synthesis of 2,2'-bisindole-3-acetic acid derivatives from
aldimines derived from 2-aminocinnamic acid derivatives and indole-2
carboxaldehyde was developed via a cyanide-catalyzed imino-Stetter reaction. With
this protocol, the divergent total syntheses of arcyriaflavin A, a representative
indolocarbazole natural product, and calothrixin B, a representative indolo[3,2
j]phenanthridine natural product, were completed using a 2,2'-bisindole-3-acetic
acid derivative as the common intermediate.
PMID- 28520442
TI - T-2 Toxin-3alpha-glucoside in Broiler Chickens: Toxicokinetics, Absolute Oral
Bioavailability, and in Vivo Hydrolysis.
AB - Due to the lack of information on bioavailability and toxicity of modified
mycotoxins, current risk assessment on these modified forms assumes an identical
toxicity of the modified form to their respective unmodified counterparts.
Crossover animal trials were performed with intravenous and oral administration
of T-2 toxin (T-2) and T-2 toxin-3alpha-glucoside (T2-G) to broiler chickens.
Plasma concentrations of T2-G, T-2, and main phase I metabolites were quantified
using a validated liquid chromatography-tandem mass spectrometry method with a
limit of quantitation for all compounds of 0.1 ng/mL. Resulting plasma
concentration-time profiles were processed via two-compartmental toxicokinetic
models. No T-2 triol and only traces of HT-2 were detected in the plasma samples
after both intravenous and oral administration. The results indicate that T-2 has
a low absolute oral bioavailability of 2.17 +/- 1.80%. For T2-G, an absorbed
fraction of the dose and absolute oral bioavailability of 10.4 +/- 8.7% and 10.1
+/- 8.5% were observed, respectively. This slight difference is caused by a
minimal (and neglectable) presystemic hydrolysis of T2-G to T-2, that is, 3.49 +/
1.19%. Although low, the absorbed fraction of T2-G is 5 times higher than that
of T-2. These differences in toxicokinetics parameters between T-2 and T2-G
clearly indicate the flaw in assuming equal bioavailability and/or toxicity of
modified and free mycotoxins in current risk assessments.
PMID- 28520444
TI - Enhancing Singlet Fission Dynamics by Suppressing Destructive Interference
between Charge-Transfer Pathways.
AB - We apply a real-time path-integral approach to investigate the charge-transfer
(CT)-mediated singlet fission quantum dynamics in a model pentacene dimer. Our
path-integral method gives reliable fission dynamics across various reaction
regimes as well as a broad range of reorganization energies and temperatures.
With this method, we investigated the destructive interference between the two CT
mediated fission pathways and discovered two mechanisms that can suppress this
deleterious effect. First, increasing the energy gap between the two CT states
effectively shuts down the high-lying CT pathway, leaving a better functioning
low-lying CT pathway with a minimum amount of destructive interference. Second,
intermolecular vibrations induce electronic coupling fluctuations, such that the
destructive cancellations due to the different signs in static electronic
couplings are suppressed. Our numerical results suggest that these two effects
can enhance the fission rate up to three times. These findings reveal promising
design principles for more efficient singlet fission materials.
PMID- 28520443
TI - Effective Interactions and Colloidal Stability of Bovine gamma-Globulin in
Solution.
AB - Interactions and phase behavior of gamma-globulins are of fundamental interest in
biophysical and pharmaceutical research, as these are among the most abundant
proteins in blood plasma. In this work, we report the characterization of the
oligomeric state of bovine gamma-globulin, the effective protein-protein
interactions, and the colloidal stability in aqueous solution as a function of
protein concentration and ionic strength. Classical biochemical techniques, such
as size exclusion chromatography (SEC) and gel electrophoresis, together with
small-angle X-ray and neutron scattering (SAXS/SANS), were employed for this
study. The results show that bovine gamma-globulin solutions are dominated by
monomer and idiotype anti-idiotype dimer. Despite the flexibility and highly
nonspherical shape of the protein, a simple model with a disk-type form factor
and a structure factor of a square-well potential provide a satisfying
description of the scattering data. The overall interactions are attractive and
the strength decreases with increasing protein concentration, or adding buffer or
salts. For higher protein volume fraction (>7%), the model would imply a strong
particle-particle correlation which does not appear in the experimental data.
This mismatch is most likely due to the smearing effect of the conformation
change of proteins in solution. The stability of gamma-globulin solutions is
highly sensitive to protein concentration, ionic strength, and the type of added
salts, such as NaCl, Na2SO4, and NaSCN. For solutions below 50 mg/mL and at low
ionic strengths (<0.1 M), protein aggregation is most likely due to
subpopulations of IgG molecules with attractive patches of complementary surface
charge. This effect is reduced for higher protein concentration due to self
buffering effects. For high ionic strength (>1 M), typical salting-in (with
NaSCN) and salting-out effects (with NaCl and Na2SO4) are observed. Results are
further discussed in comparison with current studies in the literature on
monoclonal antibodies.
PMID- 28520445
TI - Telodendrimers for Physical Encapsulation and Covalent Linking of Individual or
Combined Therapeutics.
AB - New therapeutics for glioblastoma multiforme and our ability to deliver them
using efficient nanocarriers constitute topical areas of research. We report a
comparative study of temozolomide and quercetin in the treatment of glioblastoma
(GBM) in three-dimensions, and their incorporation into micelles obtained from
synthetically articulated architectural copolymers, and a commercially available
linear polymer poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PEG-PLGA). A
versatile synthetic methodology to telodendrimers, which can be easily adapted to
the needs of other therapeutic interventions, is presented. These dendritic block
copolymers self-assemble into micelles and offer a platform for single or
combination drug therapy. Telodendrimer micelles loaded with quercetin did not
exhibit superior cell killing effect over the free drug, but acetazolamide, an
inhibitor carbonic anhydrase IX, significantly reduced GBM cell viability in 3D
spheroids. Results from these studies show that high loading of drugs into
telodendrimer micelles requires a physical fit between the biologically active
agent and telodendrimer nanocarrier, and points toward new possibilities for
incorporation of chemotherapeutic and other agents to enhance their
effectiveness.
PMID- 28520447
TI - [Controversies around QALYs].
AB - The paper summarizes the criticisms of the QALY concept utilization in health
economic evaluations that has been growing stronger in the last years. Despite of
its limitations, the QALY concept has been routinely used in many countries incl.
the Czech Republic. However, some states disapproved QALYs as an optimizing
criterion at the level of their political decisions. The critical reflection
concerns both the theoretical and the experimental issues. Based on a literary
review, fundamental arguments against the concept are summarized, and a synthesis
of material objections is presented. The critical arguments focus on the
foundations of the QALY concept in the economic theory, some ethical principles,
inconsistencies and technical imperfections of the quality-of-life measurement
tools used in QALY calculations, the substitution rule, differences between
various diagnoses, and disregarding some other important parameters. As a whole,
the critics' arguments can be judged as quite strong. The future will show
whether the critical arguments summarized in this paper will lead to a
development of alternative tools that have a potential of eliminating
imperfections in QALYs, and consequently provide more complex data for the
decision process.Key words: cost-effectiveness - health technology assessment -
HTA - QALY - utility measure for medical interventions.
PMID- 28520446
TI - [Diabetic foot syndrome: importance of calf muscles MR spectroscopy in the
assessment of limb ischemia and effect of revascularization].
AB - AIM: The standard method for assessment of effect of revascularization in
patients with diabetic foot (DF) and critical limb ischemia (CLI) is
transcutaneous oxygen pressure (TcPO2). Phosphorus magnetic resonance
spectroscopy (31P MRS) enables to evaluate oxidative muscle metabolism that could
be impaired in patients with diabetes and its complications. The aim of our study
was to compare MRS of calf muscle between patients with DF and CLI and healthy
controls and to evaluate the contribution of MRS in the assessment of the effect
of revascularization. METHODS: Thirty-four diabetic patients with DF and CLI
treated either by autologous cell therapy (ACT; 15 patients) or percutaneous
transluminal angioplasty (PTA; 12 patients) in our foot clinic during 2013-2016
and 19 healthy controls were included into the study. TcPO2 measurement was used
as a standard method of non-invasive evaluation of limb ischemia. MRS
examinations were performed using the whole-body 3T MR system 1 day before and 3
months after the procedure. Subjects were examined in a supine position with the
coil fixed under the m. gastrocnemius. MRS parameters were obtained at rest and
during the exercise period. Rest MRS parameters of oxidative muscle metabolism
such as phosphocreatine (PCr), inorganic phosphate (Pi), phosphodiesters (PDE),
adenosine triphosphate (ATP), dynamic MRS parameters such as recovery constant
PCr (tauPCr) and mitochondrial capacity (Qmax), and pH were compared between
patients and healthy controls, and also before and 3 months after
revascularization. RESULTS: Patients with CLI had significantly lower PCr/Pi (p <
0.001), significantly higher Pi and pH (both p < 0.01), significantly lower Qmax
and prolonged tauPCr (both p < 0.001) in comparison with healthy controls. We
observed a significant improvement in TcPO2 at 3 months after revascularization
(from 26.4 +/- 11.7 to 39.7 +/- 17.7 mm Hg, p < 0.005). However, the rest MRS
parameters did not change significantly after revascularization. In individual
cases we observed improvement of dynamic MRS parameters. There was no correlation
between MRS parameters and TcPO2 values. CONCLUSION: Results of our study show
impaired oxidative metabolism of calf muscles in patients with CLI in comparison
with healthy controls. We observed an improvement in dynamic MRS parameters in
individual cases; this finding should be verified in a large number of patients
during longer follow-up.Key words: autologous cell therapy - critical limb
ischemia - diabetic foot - MR spectroscopy.
PMID- 28520448
TI - [The role of cardiovascular magnetic resonance imaging in the diagnosis of
hypertrophic cardiomyopathy. Part II].
AB - Hypertrophic cardiomyopathy is currently understood as a group of diseases with
left ventricular hypertrophy, which are not based on adaptive mechanisms. The
first part of the review details the possibility of cardiac magnetic resonance in
the diagnosis of sarcomeric forms of hypertrophic cardiomyopathy, the second part
will focus on the possibilities of distinguishing the sarcomeric forms from their
phenocopies.Key words: cardiac magnetic resonance - hypertrophic cardiomyopathy -
phenocopies.
PMID- 28520449
TI - [Novelties in the treatment of heart failure].
AB - Heart failure (HF) is a complex clinical syndrome which is manifested by
characteristic symptoms and objective signs of cardiac insufficiency. The
incidence of HF, particularly its chronic form, is estimated 0.4-2 % in the
central and western Europe, with an increase in higher age groups, affecting 10
20 % of the population aged over 80. With respect to its growing incidence and
prevalence, novel modalities of pharmacological and non-pharmacological treatment
are being developed in order to improve quality of life and survival of the
affected patients. This review based on up-to-date guidelines focuses in the
first part on brief description of the possibilities of diagnosing heart failure,
including the novelties arising out from the latest clinical and preclinical
studies (such as soluble ST2, FSTL1, etc), further it concentrates on innovations
in pharmacological treatment of chronic (ivabradine, ARNI, gliflozins) and acute
(ularitide, serelaxin, nesiritide) HF. The last part provides an overview of
available non-pharmacological HF therapeutics options (modulation of cardiac
contraction, influencing the activity of sympathetic and parasympathetic nervous
systems and permanent and temporary device support).Key words: ARNI - ECMO -
gliflozins - heart failure - modulation of sympathetic and parasympathetic
nervous systems - sacubitril-valsartan - therapy.
PMID- 28520450
TI - [AT1 blockers - comparability with ACE inhibitors].
AB - The reduction in overall mortality, cardiovascular mortality and the occurrence
of myocardial infarction in patients treated with AT1 blockers is comparable with
the use of ACE inhibitors. In addition, there is a lower proportion of AT1
blockers withdrawal of treatment due to adverse reactions.Key words: ACE
inhibitors - AT1 blockers - cardioprotection - hypertension - renin-angiotensin
aldosteron system.
PMID- 28520451
TI - [How to create cooperative patient for antihypertensive and hypolipidemic
therapy].
AB - Patient drug adherence is a major problem especially in the prevention of
cardiovascular disease of atherosclerotic origin. On one hand, antihypertensive
drugs and hypolipidemic drugs/statins are among the most successful, ones the
other hand, they are among the drugs which are most frequently skipped by the
patients. Improvement could be realized by education of patients, more frequent
follow-ups, as well as by the use of new technologies involving specific
dispensers and other, even more sophisticated methods. Nevertheless, among the
most successful strategies is the simplification of medication, particularly the
use of drugs with a longer half-life and the use of combination of several drugs
in a single tablet. Therefore, we have quite wide range of options to improve
patient compliance. However, some disadvantages should be kept in mind associated
with these techniques. The aim of this article is to discuss potential problems
and solutions associated with patient adherence/compliance with respect to
antihypertensive and hypolipidemic treatment with an emphasis on practical
approach.Key words: drug adherence - dyslipidemia - hypertension -
pharmacotherapy.
PMID- 28520453
TI - [Indeterminate cell histiocytosis - disappearance of skin infiltration following
electron beam therapy and an application of 2-chlorodeoxyadenosine: case report].
AB - Indeterminate cell histiocytosis is a rare disease belonging to the group of
malignant histiocytic diseases. The disease predominantly affects the skin. The
disease appeared in the described patient at the age of 80 years. Morphs began to
develop on the skin and rapidly spread over the whole body including the face.
Only the hands and feet were left uncovered. The patients skin samples were taken
from 2 sites for histological examination. The resulting conclusion was
indeterminate cell histiocytosis. The treatment we chose was analogous to the
procedures for Langerhans cell histiocytosis. We chose PUVA phototherapy as the
first-line treatment. This treatment is frequently efficient for skin forms of
Langerhans cell histiocytosis. In the described case, however, PUVA phototherapy
did not influence the disease activity at all. As the second-line treatment, we
used low-energy electron beam irradiation in the total dose of 36.2 Gy. This
treatment had a positive impact, morphs began to diminish and slowly disappear
from the skin. But they have not disappeared completely, therefore we assessed
the treatment effect of the radiotherapy itself as partial remission of the
disease. Within the third-line treatment, we used 2-chlorodeoxyadenosine in a
dose of 5 mg/m2/per day, administered via subcutaneous injection over 5
consecutive days in monthly intervals. There were three cycles of this treatment
administered overall. The treatment with 2-chlorodeoxyadenosine was tolerated
without any adverse effects. The patient aged 82 years was only administered 3
cycles of 2-chlorodeoxyadenosine. When after the 3rd cycle the skin was free from
any pathological morphs and only some pigmentation spots remained, we finished
the treatment. The skin expressions of indeterminate cell histiocytosis
completely disappeared after electron beam irradiation and the following
administration of 3 cycles of 2-chlorodeoxyadenosine. The remission was short,
however, after 6 months the disease recurred and the treatment is planned to
resume. We assume the disease regresses following administration of 2
chlorodeoxyadenosine, but more than 3 treatment cycles will probably be needed to
reach a longer-term response.Key words: electron beam irradiation - indeterminate
cell histiocytosis - 2-chlorodeoxyadenosine.
PMID- 28520452
TI - [Relapsing autoimmune pancreatitis type 1: case report].
AB - Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis, classified
into 2 subtypes - AIP type 1 and AIP type 2. We present a case of a 31-years-old
female admitted to our institution with upper abdominal pain and obstructive
jaundice. Endoscopic retrograde cholangiopancreatoscopy (ERCP) revealed stenosis
of intrapancreatic distal bile duct. Diffuse parenchymal enlargement and typical
features of AIP were shown by computed tomography (CT) and endoscopic
ultrasonography (EUS). The patient's serum IgG4 was elevated at 3.8 g/l (range
0.08-1.4 g/l). She was diagnosed with AIP type 1 and treated with prednisone
(initial dose of 30 mg per day, then tapered by 5 mg/day every week). The
maintenance dose of 5 mg per day was continued for 6 months. Despite clinical and
radiological remission, serum levels of IgG4 remained elevated. The patient
experienced disease relapse 25 months after first attack. Moreover, new finding
of calcifications occured in pancreas. The relapse was managed with
corticosteroids and maintenance immunosupression with azathioprin was started.
Literature review on risk factor of relapse, long-term immunosupressive therapy
indication and optimal follow-up of AIP type 1 patients are discussed.Key words:
autoimmune pancreatitis type 1 - long-term follow-up - relapse - therapy.
PMID- 28520454
TI - Acupuncture "Rewires" the Brain ... with Lasting Effects.
PMID- 28520455
TI - Quantitative determination of AVI-7100 (Radavirsen), a phosphorodiamidate
morpholino oligomer (PMOplus(r) ), in human plasma using LC-MS/MS.
AB - AIM: AVI-7100 (Radavirsen) is a 20-mer phosphorodiamidate morpholino oligomer
(PMOplus(r)) for the treatment of influenza. Results/methodology: An automated
solid-phase extraction method was used to extract plasma samples (200 MUl). The
extracts were analyzed using liquid chromatography coupled with tandem mass
spectrometry under the positive ionization mode. This method was fully validated
over the calibration curve range of 5.00-1000 ng/ml. The between-run precision
and accuracy ranged from 0.0 to 5.2% relative standard deviation and 91.6 to
100.0% of nominal for all quality control concentrations, including the lower
limit of quantitation. DISCUSSION/CONCLUSION: This is the first liquid
chromatography coupled with tandem mass spectrometry method for the measurement
of AVI-7100 concentrations in human plasma. It has been used to support regulated
bioanalysis.
PMID- 28520457
TI - Measuring and using free drug concentrations: has there been 'real' progress?
PMID- 28520456
TI - Development and validation of a micellar liquid chromatographic method to
determine three antitumorals in plasma.
AB - AIM: A micellar liquid chromatographic method to determine several anticancer
drugs (pazopanib, dabrafenib and regorafenib) in plasma was developed and
validated by the guidelines of the EMA. EXPERIMENTAL: Plasma samples were
directly injected, after a 1/5-dilution in a micellar solution. The drugs were
resolved in <18 min using a C18 column. The mobile phase was an aqueous solution
of 0.12 M SDS - 2% 1-pentanol, buffered at pH 7. The detection was performed by
absorbance at 260 nm. RESULTS: The values of the main validation parameters were:
LOD (0.1-1 mg/l), calibration range (0.2-2 to 80 mg/l), accuracy (-12.5 to
+11.7%) and precision (<11.9%). CONCLUSION: The procedure was conducted by
minimum cost, effort, manipulation, time and quantity of hazardous chemicals. The
method was useful to determine the drugs at their respective target
concentrations, and was found useful for clinical analysis.
PMID- 28520458
TI - Anchored Transosseous-Equivalent Versus Anchorless Transosseous Rotator Cuff
Repair: A Biomechanical Analysis in a Cadaveric Model.
AB - BACKGROUND: The original approach for the repair of torn rotator cuffs involved
an open technique with sutures passing through the greater tuberosity and tendon.
The development of suture anchors allowed for an all-arthroscopic approach with
anchor configurations attempting to re-create a transosseous fixation pattern.
Presently, an arthroscopic approach can be combined with a transosseous suture
configuration without using anchors. PURPOSE: To evaluate cyclic loading,
ultimate load to failure, and the failure mechanisms of transosseous-equivalent
(TOE) repair with anchors and anchorless transosseous (AT) repair of rotator cuff
tears. STUDY DESIGN: Controlled laboratory study. METHODS: Supraspinatus tears
(25 mm) were created in 20 fresh-frozen, human cadaveric shoulders, which were
randomized to TOE or AT repair (10 in each group, paired experimental design).
Biomechanical testing was performed with an initial preload, cyclic loading, and
load to failure. Optical markers were used to monitor gap formation in 3 planes,
and the failure mode was recorded. Paired t tests were used to make comparisons
of biomechanical parameters between the groups. Multinomial logistic regression
was used to compare failure modes between the groups. Significance was set to
.05. RESULTS: The TOE group had a significantly higher mean (+/-SD) ultimate
failure load (578.5 +/- 123.8 N) than the AT group (468.7 +/- 150.9 N) ( P =
.034). The TOE group also had a significantly less mean first-cycle excursion
(2.97 +/- 1.97 mm) than the AT group (4.70 +/- 2.04 mm) ( P = .046). There were
no significant differences between the groups in cyclic elongation or linear
stiffness during cyclic loading. Primary modes of failure were a type 2 tendon
tear with medial tendon disruption in the TOE group (7/10) and a type 1 tendon
tear with lateral tendon disruption in the AT group (6/10). CONCLUSION: TOE
repair resulted in a significantly higher mean failure load compared with AT
repair in a cadaveric model. The most common modes of failure were a type 2
tendon tear in the TOE group and a type 1 tendon tear in the AT group. CLINICAL
RELEVANCE: A higher mean failure load in TOE versus AT constructs may come at the
cost of a less favorable failure mode adjacent to medial anchors at the
musculotendinous junction, potentially making revision difficult.
PMID- 28520459
TI - Feedback from the EBF - Focus Workshop: bringing assay validation and analysis of
biomarkers into practice.
AB - European Bioanalysis Forum Focus Workshop, Lisbon, Portugal, 9-10 June 2016 At
the recent European Bioanalysis Forum's Focus Workshop 'Bringing Assay Validation
and Analysis of Biomarkers into Practice', the discussion on best practice for
biomarker assay validation continued. Both the presentations and the adjacent
panel discussions yielded valuable food for thought for the broader bioanalytical
community. The present conference report summarizes the essence from these
discussions and from the proposals or conclusions made by all delegates on how to
increase the necessary connectivity of the stakeholders involved in the
bioanalysis of biomarkers.
PMID- 28520460
TI - The Influence of Body Mass Index on Outcomes After Hip Arthroscopic Surgery With
Capsular Plication for the Treatment of Femoroacetabular Impingement.
AB - BACKGROUND: It remains unknown how variations in body mass index (BMI) influence
outcomes after primary hip arthroscopic surgery with capsular plication for
femoroacetabular impingement (FAI). PURPOSE: To evaluate the effect that abnormal
BMI (namely, overweight, obese, morbidly obese, and underweight) versus normal
weight has on patient-reported clinical outcomes more than 2 years
postoperatively from primary hip arthroscopic surgery with capsular plication by
a single surgeon. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A
clinical repository containing patients undergoing primary hip arthroscopic
surgery for FAI between January 1, 2012, and January 1, 2014, with a minimum 2
year follow-up was queried. Outcome measures included the Hip Outcome Score (HOS)
Activities of Daily Living (ADL), HOS-Sports, modified Harris Hip Score (mHHS),
visual analog scale (VAS) for pain; satisfaction, and Patient Acceptable
Symptomatic State (PASS) for the HOS-ADL; scores were collected preoperatively
and at 3 months, 1 year, and minimum 2 years postoperatively. Included patients
were segregated by preoperative BMI into the following categories: underweight
(<18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), obese
(30.0-34.9 kg/m2), and morbidly obese (>=35.0 kg/m2). A multivariate logistic
regression model controlling for patient demographics and disease severity was
used to identify independent associations between BMI categories and outcomes. A
Bonferroni adjustment lowered the threshold for significance to P < .01. RESULTS:
There were 409 hips in 381 patients appropriate for study inclusion: 7
underweight, 197 normal BMI, 130 overweight, 31 obese, and 16 morbidly obese. The
mean age was 33.1 +/- 12.1 years, with 232 (61%) female patients. At 2 years
postoperatively, significant differences in the trend among HOS-ADL, HOS-Sports,
and mHHS scores were evident, with normal BMI patients, followed by underweight
patients, demonstrating greater scores than their overweight, obese, and morbidly
obese counterparts. Obese patients demonstrated lower satisfaction scores than
normal BMI patients. Overweight, obese, and morbidly obese patients had lower
improvements in VAS pain scores compared with normal BMI patients. Increasing BMI
(not subdivided into the 5 BMI categories) was associated with a higher infection
risk (mean BMI for infections: 32.3 +/- 9.8 kg/m2 vs mean BMI for noninfections:
25.2 +/- 4.8 kg/m2; P = .0035). However, with multivariate analysis, no
significant differences in patient clinical outcomes between the BMI categories
met the threshold for significance. Among obese patients (BMI >=30.0 kg/m2), no
specific risk factors were found to be significantly associated with decreases in
the change in VAS, HOS-ADL, HOS-Sports, mHHS, satisfaction, or PASS for the HOS
ADL scores. However, because of the small cohort sizes at the extremes of the BMI
categories, this analysis may have been underpowered to identify a significant
difference in underweight or morbidly obese patients. CONCLUSION: In the current
cohort, there were multiple potential confounding variables, and while some
clinical differences were observed initially (higher HOS-ADL, HOS-Sports, and
mHHS scores for normal BMI patients than overweight and obese patients at 2 years
postoperatively; lower satisfaction scores for obese patients than normal BMI
patients; and lower improvement in VAS pain scores for overweight, obese, and
morbidly obese patients when compared with normal BMI patients), after
multivariate analysis, no associations were observed between BMI and clinical
outcomes after hip arthroscopic surgery with capsular plication for FAI.
PMID- 28520461
TI - Clinical Outcome After Arthroscopic Debridement and Microfracture for
Osteochondritis Dissecans of the Capitellum.
AB - BACKGROUND: Various surgical treatment techniques have been developed to treat
capitellar osteochondritis dissecans; however, the optimal technique remains the
subject of ongoing debate. PURPOSE: To evaluate clinical outcomes after
arthroscopic debridement and microfracture for advanced capitellar
osteochondritis dissecans. STUDY DESIGN: Case series; Level of evidence, 4.
METHODS: Between 2008 and 2015, the authors followed 77 consecutive patients (81
elbows) who underwent arthroscopic debridement and microfracture, and loose body
removal if needed, for advanced capitellar osteochondritis dissecans. Seventy-one
patients (75 elbows) with a minimum follow-up of 1 year were included. The mean
age was 16 years (SD, +/-3.3 years; range, 11-26 years) and the mean follow-up
length was 3.5 years (SD, +/-1.9 years; range, 1-8.2 years). Based on CT and/or
MRI results, 71 lesions were classified as unstable and 4 as stable. Clinical
elbow outcome (pain, function, and social-psychological effect) was assessed
using the Oxford Elbow Score (OES) at final follow-up (OES range, 0-48). Range of
motion and return to sports were recorded. Multivariable linear regression
analysis was performed to determine predictors of postoperative OES. RESULTS:
Intraoperatively, there were 3 grade 1 lesions, 2 grade 2 lesions, 10 grade 3
lesions, 1 grade 4 lesion, and 59 grade 5 lesions. The mean postoperative OES was
40.8 (SD, +/-8.0). An open capitellar physis was a predictor of better elbow
outcome (5.8-point increase; P = .025), as well as loose body removal/grade 4-5
lesions (6.9-point increase; P = .0020) and shorter duration of preoperative
symptoms (1.4-point increase per year; P = .029). Flexion slightly improved from
134 degrees to 139 degrees ( P < .001); extension deficit slightly improved
from 8 degrees to 3 degrees ( P < .001). Pronation ( P = .47) and supination
did not improve ( P = .065). Thirty-seven patients (55%) returned to their
primary sport at the same level, and 5 patients (7%) returned to a lower level.
Seventeen patients (25%) did not return to sport due to elbow-related symptoms,
and 10 patients (13%) did not return due to non-elbow-related reasons. No
complications were recorded. CONCLUSION: Arthroscopic debridement and
microfracture for advanced capitellar osteochondritis dissecans provide good
clinical results, especially in patients with open growth plate, loose body
removal, and shorter duration of symptoms. However, only 62% of patients in this
study returned to sports.
PMID- 28520462
TI - Activity-based proteomics in bioanalysis: past, present and future.
PMID- 28520463
TI - A Preclinical Assessment of Early Continuous Passive Motion and Treadmill
Therapeutic Exercises for Generating Chondroprotective Effects After Anterior
Cruciate Ligament Rupture.
AB - BACKGROUND: Anterior cruciate ligament (ACL) injury is a well-known risk factor
for the development of posttraumatic osteoarthritis (PTOA). However, whether
using continuous passive motion (CPM) with or without additional treadmill
exercise (TRE) in early ACL injury might provide chondroprotective effects and
further decrease the risk of PTOA has yet to be determined. HYPOTHESIS: CPM may
offer an enhanced chondroprotective effect, but TRE may attenuate that effect due
to the mechanical stress on the joint and inflammatory cytokines in the joint.
STUDY DESIGN: Controlled laboratory study. METHODS: Thirty adult New Zealand
White male rabbits were randomly allocated to sedentary (SED), CPM, TRE, or
CPM+TRE groups. Each rabbit underwent an ACL transection (ACLT) on the right
knee, with the contralateral knee used as an internal control (sham). The 4 joint
surfaces (ie, medial and lateral femoral condyles and tibial plateaus) were
evaluated 4 weeks after surgery for gross appearance, histological
characteristics, and quantitative osteoarthritis (OA) scores. RESULTS: Overall,
at the end of testing, the CPM group experienced the best protective therapeutic
effects in all compartments. In gross appearance, CPM resulted in normal
articular surfaces, while the TRE and SED groups exhibited surface abrasion.
Histological analysis showed significant differences in articular cartilage
status. The CPM group had significantly better histological OA scores ( P < .01),
corresponding to the smoothest cartilage surface and sound chondrocyte and
collagen arrangement. This group also showed abundant glycosaminoglycan (GAG)
content and a sound growth microenvironment, with significantly lower expression
levels of the inflammatory cytokine tumor necrosis factor alpha and the apoptotic
marker caspase 3. In contrast, the TRE and SED groups showed several features of
damage: distinct graded cartilage abrasion; damaged collagen fibers,
corresponding to noticeable collagen type X (osteoarthritic cartilage); reduced
cartilage thickness; fewer cartilaginous cells; and the appearance of chondrocyte
clusters. These groups also showed loss of GAG, corresponding to higher levels of
inflammatory cytokines and apoptosis of articular chondrocytes. Furthermore, the
CPM+TRE group displayed visible pathological changes in the superficial
cartilage, indicating that early loading exercise may contribute to
osteoarthritis. The sham treatment showed no difference in the changes in all
compartments between groups. CONCLUSION: Immediate CPM therapy produces a
superior in situ microenvironment for reducing the occurrence of PTOA after ACL
injury without reconstruction in rabbits. CLINICAL RELEVANCE: These data suggest
that immediate application of CPM therapy may be necessary to create a sound
microenvironment in joints and possibly to decrease the risk of PTOA without or
while awaiting ACL reconstruction. In contrast, both early active loading
exercise and inactivity lead to the development of PTOA.
PMID- 28520464
TI - Suvorexant for the Treatment of Insomnia in Adolescents.
AB - OBJECTIVES: Suvorexant is the first dual orexin receptor antagonist for treating
insomnia. This study aimed to evaluate the tolerability, efficacy, and safety of
suvorexant on insomnia in adolescents. METHODS: Thirty patients (8 male and 22
female; mean standard deviation age: 15.7 +/- 2.4 years; range: 10-20) with
insomnia were administered suvorexant. Clinical background, persistence rate, the
Clinical Global Impression (CGI), and the Athens Insomnia Scale (AIS) were
compared between patients who continued and discontinued suvorexant treatment.
RESULTS: Seventeen patients (56.7%) successfully continued taking suvorexant.
Among the 13 patients who did not continue treatment, 5 patients were lost to
follow-up. Of the remaining eight who did not continue treatment, four decided to
discontinue of their own accord, two decided to discontinue due to lack of
effectiveness, and two decided to discontinue due to adverse reaction, namely
abnormal dreams. Among patients who completed the study, CGI significantly
decreased from 3.6 +/- 0.8 to 3.1 +/- 0.9 (p = 0.014). The score of sleep quality
in AIS was significantly higher among the patients who discontinued suvorexant
than those who continued suvorexant (p = 0.02). CONCLUSION: Our results indicate
that suvorexant could be considered a treatment option for adolescents.
PMID- 28520465
TI - Mesenchymal Stem/Stromal Cells in Regenerative Medicine: Past, Present, and
Future.
AB - The concept of Regenerative Medicine combined with Cell based Therapy and Tissue
Engineering represents the fourth pillar of healthcare and provides a promising
approach for the treatment of serious diseases. Recently, cell based therapies
are focused on the use of mesenchymal stem/stromal cells (MSCs). Human MSCs, that
represent a mesoderm derived population of progenitors, are easily expanded in
culture. They are capable to differentiate into osteoblasts, chondrocytes, and
adipocytes and exhibit the potential to repair or regenerate damaged tissues. The
best characterized source of human MSCs to date is the bone marrow; recently,
fetal sources, such as amniotic fluid, umbilical cord, amniotic membranes, or
placenta, have also attracted increased attention. Thus, MSCs may represent a
valuable tool for tissue repair and cell therapeutic applications. To this end,
the main focus of this review is to summarize and evaluate the key
characteristics, the sources, and the potential use of MSCs in therapeutic
approaches and modalities.
PMID- 28520466
TI - Development and validation of a highly sensitive gradient chiral separation of
pramipexole in human plasma by LC-MS/MS.
AB - AIM: Development of a high-sensitivity chiral LC-MS/MS method was required to
evaluate a combination of pramipexole (S-PPX) and its enantiomer dexpramipexole
(R-PPX) in a proposed clinical trial. The previously available methods suffered
from low sensitivity for the (S)-enantiomer in the presence of the more abundant
(R)-enantiomer. Based on the projected dosing regimen in the clinical trial, a
5000-fold improvement in sensitivity was required for the (S)-enantiomer.
METHODOLOGY: Spiked human plasma samples were extracted by liquid-liquid
extraction using ethyl acetate and injected onto a CHIRALPAK ID column under pH
gradient conditions. CONCLUSION: An improved analytical method was developed and
validated with a final LLQ for (S)-PPX of 0.1 ng/ml in the presence of 2000 ng/ml
of (R)-PPX.
PMID- 28520467
TI - Challenges in metabolomics-based disease molecular classification: an analytical
perspective.
PMID- 28520468
TI - The Hierarchy of Brain Networks Is Related to Insulin Growth Factor-1 in a Large,
Middle-Aged, Healthy Cohort: An Exploratory Magnetoencephalography Study.
AB - Recently, a large study demonstrated that lower serum levels of insulin growth
factor-1 (IGF-1) relate to brain atrophy and to a greater risk for developing
Alzheimer's disease in a healthy elderly population. We set out to test if
functional brain networks relate to IGF-1 levels in the middle aged. Hence, we
studied the association between IGF-1 and magnetoencephalography-based functional
network characteristics in a middle-aged population. The functional connections
between brain areas were estimated for six frequency bands (delta, theta, alpha1,
alpha2, beta, gamma) using the phase lag index. Subsequently, the topology of the
frequency-specific functional networks was characterized using the minimum
spanning tree. Our results showed that lower levels of serum IGF-1 relate to a
globally less integrated functional network in the beta and theta band. The
associations remained significant when correcting for gender and systemic effects
of IGF-1 that might indirectly affect the brain. The value of this exploratory
study is the demonstration that lower levels of IGF-1 are associated with brain
network topology in the middle aged.
PMID- 28520469
TI - Carotid versus coronary atherosclerosis burdens in acute compared with chronic
symptomatic coronary artery disease.
AB - Prediction of coronary events remains elusive. Carotid atherosclerosis may be a
surrogate for coronary risk, as carotid and coronary diseases occur
simultaneously - albeit at times with a weak association - depending on clinical
presentation. We investigated carotid and coronary atherosclerosis in men with
new-onset unstable coronary artery disease (CAD) presenting with acute ST-segment
elevation myocardial infarction (STEMI) vs. long-standing severe chronic stable
angina (CSA). Bilateral carotid artery and 3-vessel coronary artery
atherosclerosis burdens were measured within 1 month, respectively, by 3D
volumetric carotid magnetic resonance imaging and coronary angiography-derived
modified CASS-50 score. Men with STEMI (n = 50) and long-standing CSA (n = 50),
matched for age, were enrolled (58.6 +/- 8.8 years). All of them had carotid
atherosclerosis. Atherosclerosis burden was greater in the carotid arteries of
STEMI vs. CSA (wall volume: 196.2 +/- 44.4 vs. 169.2 +/- 38.0 mm3/4 mm, p =
0.002), but greater in the coronary arteries of CSA vs. STEMI (modified CASS-50
score: 3 vs. 1, p < 0.0001). Normalized wall index (NWI) of internal carotid was
associated with modified CASS-50 score in STEMI (rho = 0.40, p = 0.022) and in
CSA (rho = -0.39, p = 0.031). Carotid atherosclerosis was observed in all CAD
patients, and atherosclerosis burden in carotid and in coronary arteries varied
according to clinical presentation.
PMID- 28520471
TI - ?
PMID- 28520473
TI - A New Method and Mass-Spectrometric Instrument for Extraterrestrial Microbial
Life Detection Using the Elemental Composition Analyses of Martian Regolith and
Permafrost/Ice.
AB - We propose a new technique for the detection of microorganisms by elemental
composition analyses of a sample extracted from regolith, permafrost, and ice of
extraterrestrial bodies. We also describe the design of the ABIMAS instrument,
which consists of the onboard time-of-flight laser mass-reflectron (TOF LMR) and
the sample preparation unit (SPU) for biomass extraction. This instrument was
initially approved to fly on board the ExoMars 2020 lander mission. The
instrument can be used to analyze the elemental composition of possible
extraterrestrial microbial communities and compare it to that of terrestrial
microorganisms. We have conducted numerous laboratory studies to confirm the
possibility of biomass identification via the following biomarkers: P/S and Ca/K
ratios, and C and N abundances. We underline that only the combination of these
factors will allow one to discriminate microbial samples from geological ones.
Our technique has been tested experimentally in numerous laboratory trials on
cultures of microorganisms and polar permafrost samples as terrestrial analogues
for martian polar soils. We discuss various methods of extracting microorganisms
and sample preparation. The developed technique can be used to search for and
identify microorganisms in different martian samples and in the subsurface of
other planets, satellites, comets, and asteroids-in particular, Europa, Ganymede,
and Enceladus. Key Words: Mass spectrometry-Life-detection instruments-Biomarkers
Earth Mars-Biomass spectra. Astrobiology 17, 448-458.
PMID- 28520474
TI - Survival of Deinococcus geothermalis in Biofilms under Desiccation and Simulated
Space and Martian Conditions.
AB - Biofilm formation represents a successful survival strategy for bacteria. In
biofilms, cells are embedded in a matrix of extracellular polymeric substances
(EPS). As they are often more stress-tolerant than single cells, biofilm cells
might survive the conditions present in space and on Mars. To investigate this
topic, the bacterium Deinococcus geothermalis was chosen as a model organism due
to its tolerance toward desiccation and radiation. Biofilms cultivated on
membranes and, for comparison, planktonically grown cells deposited on membranes
were air-dried and exposed to individual stressors that included prolonged
desiccation, extreme temperatures, vacuum, simulated martian atmosphere, and UV
irradiation, and they were exposed to combinations of stressors that simulate
space (desiccation + vacuum + UV) or martian (desiccation + Mars atmosphere + UV)
conditions. The effect of sulfatic Mars regolith simulant on cell viability
during stress was investigated separately. The EPS produced by the biofilm cells
contained mainly polysaccharides and proteins. To detect viable but nonculturable
(VBNC) cells, cultivation-independent viability indicators (membrane integrity,
ATP, 16S rRNA) were determined in addition to colony counts. Desiccation for 2
months resulted in a decrease of culturability with minor changes of membrane
integrity in biofilm cells and major loss of membrane integrity in planktonic
bacteria. Temperatures between -25 degrees C and +60 degrees C, vacuum, and Mars
atmosphere affected neither culturability nor membrane integrity in both
phenotypes. Monochromatic (254 nm; >=1 kJ m-2) and polychromatic (200-400 nm;
>5.5 MJ m-2 for planktonic cells and >270 MJ m-2 for biofilms) UV irradiation
significantly reduced the culturability of D. geothermalis but did not affect
cultivation-independent viability markers, indicating the induction of a VBNC
state in UV-irradiated cells. In conclusion, a substantial proportion of the D.
geothermalis population remained viable under all stress conditions tested, and
in most cases the biofilm form proved advantageous for surviving space and Mars
like conditions. Key Words: Biofilms-Desiccation-UV radiation-Mars
Lithopanspermia. Astrobiology 17, 431-447.
PMID- 28520472
TI - A Study of the Microbial Spatial Heterogeneity of Bahamian Thrombolites Using
Molecular, Biochemical, and Stable Isotope Analyses.
AB - Thrombolites are buildups of carbonate that exhibit a clotted internal structure
formed through the interactions of microbial mats and their environment. Despite
recent advances, we are only beginning to understand the microbial and molecular
processes associated with their formation. In this study, a spatial profile of
the microbial and metabolic diversity of thrombolite-forming mats of Highborne
Cay, The Bahamas, was generated by using 16S rRNA gene sequencing and predictive
metagenomic analyses. These molecular-based approaches were complemented with
microelectrode profiling and in situ stable isotope analysis to examine the
dominant taxa and metabolic activities within the thrombolite-forming
communities. Analyses revealed three distinctive zones within the thrombolite
forming mats that exhibited stratified populations of bacteria and archaea.
Predictive metagenomics also revealed vertical profiles of metabolic
capabilities, such as photosynthesis and carboxylic and fatty acid synthesis
within the mats that had not been previously observed. The carbonate precipitates
within the thrombolite-forming mats exhibited isotopic geochemical signatures
suggesting that the precipitation within the Bahamian thrombolites is
photosynthetically induced. Together, this study provides the first look at the
spatial organization of the microbial populations within Bahamian thrombolites
and enables the distribution of microbes to be correlated with their activities
within modern thrombolite systems. Key Words: Thrombolites-Microbial diversity
Metagenome-Stable isotopes-Microbialites. Astrobiology 17, 413-430.
PMID- 28520475
TI - Kombucha Multimicrobial Community under Simulated Spaceflight and Martian
Conditions.
AB - Kombucha microbial community (KMC) produces a cellulose-based biopolymer of
industrial importance and a probiotic beverage. KMC-derived cellulose-based
pellicle film is known as a highly adaptive microbial macrocolony-a stratified
community of prokaryotes and eukaryotes. In the framework of the multipurpose
international astrobiological project "BIOlogy and Mars Experiment (BIOMEX),"
which aims to study the vitality of prokaryotic and eukaryotic organisms and the
stability of selected biomarkers in low Earth orbit and in a Mars-like
environment, a cellulose polymer structural integrity will be assessed as a
biomarker and biotechnological nanomaterial. In a preflight assessment program
for BIOMEX, the mineralized bacterial cellulose did not exhibit significant
changes in the structure under all types of tests. KMC members that inhabit the
cellulose-based pellicle exhibited a high survival rate; however, the survival
capacity depended on a variety of stressors such as the vacuum of space, a Mars
like atmosphere, UVC radiation, and temperature fluctuations. The critical
limiting factor for microbial survival was high-dose UV irradiation. In the tests
that simulated a 1-year mission of exposure outside the International Space
Station, the core populations of bacteria and yeasts survived and provided
protection against UV; however, the microbial density of the populations overall
was reduced, which was revealed by implementation of culture-dependent and
culture-independent methods. Reduction of microbial richness was also associated
with a lower accumulation of chemical elements in the cellulose-based pellicle
film, produced by microbiota that survived in the post-test experiments, as
compared to untreated cultures that populated the film. Key Words: BIOlogy and
Mars Experiment (BIOMEX)-Kombucha multimicrobial community-Biosignature-Biofilm
Bacterial cellulose. Astrobiology 17, 459-469.
PMID- 28520476
TI - Early Life Growth Predictors of Childhood Adiposity Trajectories and Future Risk
for Obesity: Birth to Twenty Cohort.
AB - BACKGROUND: There is growing evidence of variations in adiposity trajectories
among individuals, but the influence of early life growth patterns on these
trajectories is underresearched in low- and middle-income countries. Therefore,
our aim was to examine the association between early life conditional weight gain
and childhood adiposity trajectories. METHODS: We previously identified distinct
adiposity trajectories (four for girls and three for boys) in black South African
children (boys = 877; girls = 947). The association between the trajectories and
early life growth patterns, and future obesity risk was assessed by multivariate
linear and multinomial logistic and logistic regressions. Conditional weight gain
independent of height was computed for infancy (0-2 years) and early childhood (2
4 years). RESULTS: Conditional weight gain before 5 years of age was
significantly associated with early onset of obesity or overweight (excess
weight) BMI trajectories in both boys and girls. In girls, greater conditional
weight gain in infancy was associated with increased relative risk of being in
the early-onset obese to morbid obese trajectory, with relative risk ratios of
2.03 (95% confidence interval: 1.17-3.52) compared to belonging to a BMI
trajectory in the normal range. Boys and girls in the early-onset obesity or
overweight BMI trajectories were more likely to be overweight or obese in early
adulthood. CONCLUSIONS: Excessive weight gain in infancy and early childhood,
independent of linear growth, predicts childhood and adolescent BMI trajectories
toward obesity. These results underscore the importance of early life factors in
the development of obesity and other NCDs in later life.
PMID- 28520478
TI - Violence Against Women and Household Ownership of Radios, Computers, and Phones
in 20 Countries.
AB - OBJECTIVES: To examine the relationship between household ownership of
information and communication technologies (ICTs) and justifications for wife
beating. METHODS: Women aged 15 to 49 years in 20 countries were surveyed via
UNICEF's Multiple Indicator Cluster Surveys between 2006 and 2014. Multivariate
logistic regressions accounted for individual-, household-, and structural-level
variables. RESULTS: Household ownership of any ICT (radio, computer, fixed phone,
or mobile phone but not television) was associated with increased odds of women
rejecting wife beating. The largest association was with computer ownership:
women in homes with a computer were more likely to reject wife beating (adjusted
odds ratio [AOR] = 1.81; 97.5% confidence interval [CI] = 1.69, 1.93). Number of
ICTs was important: women in households with 1, 2, 3, 4, and 5 ICTs (vs 0) were
more likely to reject wife-beating justifications (AOR = 1.10 [97.5% CI = 1.03,
1.17]; AOR = 1.10 [97.5% CI = 1.03, 1.18]; AOR = 1.19 [97.5% CI = 1.11, 1.29];
AOR = 1.71 [97.5% CI = 1.54, 1.88]; and AOR = 2.85 [97.5% CI = 2.48, 3.26];
respectively). CONCLUSIONS: Independent of household wealth, country development,
and other sociodemographic factors, the more ICTs in a household, the more likely
that women will reject wife-beating justifications. Policymakers and program
planners should consider potential implications of ICT access relating to
intimate partner violence.
PMID- 28520477
TI - Minimum Stocking Requirements for Retailers in the Special Supplemental Nutrition
Program for Women, Infants, and Children: Disparities Across US States.
AB - OBJECTIVES: To examine state variation in minimum stocking requirements for
Special Supplemental Nutrition Program for Women, Infants, and Children (WIC)
authorized small food retailers. METHODS: We obtained minimum stocking
requirements for 50 states and the District of Columbia in 2017 from WIC Web
pages or e-mail from the state WIC agency. We developed a coding protocol to
compare minimum quantities and varieties required for 12 food and beverage
categories. We calculated the median, range, and interquartile range for each
measure. RESULTS: Nearly all states set minimum varieties and quantities of
fruits and vegetables, 100% juice, whole grain-rich foods, breakfast cereal,
milk, cheese, eggs, legumes, and peanut butter. Fewer states set requirements for
canned fish, yogurt, and tofu. Most measures had a large range in minimum
requirements (e.g., $8-$100 of fruits and vegetables, 60-144 oz of breakfast
cereal). CONCLUSIONS: WIC-participating retailers must adhere to very different
minimum stocking requirements across states, which may result in disparities in
food and beverage products available to WIC recipients. Public Health
Implications. The results provide benchmarks that can inform new local, state,
and federal program and policy efforts to increase healthy food availability in
retail settings.
PMID- 28520479
TI - Dissecting the Complexities of the Relationship Between Police Officer-Civilian
Race/Ethnicity Dyads and Less-Than-Lethal Use of Force.
AB - OBJECTIVES: To examine how sublethal use-of-force patterns vary across officer
civilian race/ethnicity while accounting for officer-, civilian-, and situational
level factors. METHODS: We extracted cross-sectional data from 5630 use-of-force
reports from the Dallas Police Department in 2014 and 2015. We categorized each
officer-civilian interaction into race/ethnicity dyads. We used multilevel, mixed
logistic regression models to evaluate the relationship between race/ethnicity
dyads and the types of use of force. RESULTS: Forty-eight percent of use-of-force
interactions occurred between a White officer and a non-White civilian (White-non
White). In bivariate models, the odds of hard-empty hand control and intermediate
weapon use were significantly higher among White-Black dyads compared with White
White dyads. The bivariate odds of intermediate weapon use were also
significantly higher among Black-Black, Hispanic-White, Black-Hispanic, and
Hispanic-Black dyads compared with White-White dyads. However, after we
controlled for individual and situational factors, the relationship between
race/ethnicity dyad and hard-empty hand control was no longer significant.
CONCLUSIONS: Although we observed significant bivariate relationships between
race/ethnicity dyads and use of force, these relationships largely dissipated
after we controlled for other factors.
PMID- 28520481
TI - On the Origins of the Electronic Cigarette: British American Tobacco's Project
Ariel (1962-1967).
AB - Electronic cigarettes are advertised as the latest technological gadget-the
smoking equivalent of smart phones. I challenge this sense of novelty by tracing
their history to the 1960s, when researchers at British American Tobacco first
recognized that smokers' brains were dependent on nicotine. This discovery
enabled British American Tobacco to develop a novel kind of smoking device under
the codename "Ariel" between 1962 and 1967. Whereas filters were meant to
eliminate specific harmful constituents of tobacco smoke, Project Ariel tried to
reduce smoking to its alkaloid essence: nicotine. By heating instead of burning
tobacco, the scientists working on Ariel managed to produce an aerosol smoking
device that delivered nicotine with very little tar while retaining the look and
feel of a cigarette. However, after receiving two patents for Ariel, British
American Tobacco ultimately decided to abandon the project to avoid endangering
cigarettes, its main product. Today, as e-cigarettes are surging in popularity,
it is worth revisiting Ariel because it is not just an episode in the history of
aerosol smoking devices but its starting point.
PMID- 28520482
TI - Foodborne Disease Outbreaks in Correctional Institutions-United States, 1998
2014.
AB - OBJECTIVES: To present the first update on the epidemiology of US foodborne
correctional institution outbreaks in 20 years. METHODS: We analyzed data from
the Centers for Disease Control and Prevention's Foodborne Disease Outbreak
Surveillance System to describe correctional institution outbreaks from 1998 to
2014 and compare them with other foodborne outbreaks. RESULTS: Two hundred
foodborne outbreaks in correctional institutions were reported, resulting in 20
625 illnesses, 204 hospitalizations, and 5 deaths. Median number of outbreak
associated illnesses per 100 000 population per year was 45 (range = 11-141)
compared with 7 (range = 4-10) for other outbreaks. These outbreaks accounted for
6% (20 625 of 358 330) of outbreak-associated foodborne illnesses. Thirty-seven
states reported at least 1 outbreak in a correctional institution. Clostridium
perfringens (28%; 36 of 128) was the most frequently reported single etiology.
The most frequently reported contributing factor was food remaining at room
temperature (37%; 28 of 76). CONCLUSIONS: Incarcerated persons suffer a
disproportionate number of outbreak-associated foodborne illnesses. Better food
safety oversight and regulation in correctional food services could decrease
outbreaks. Public Health Implications. Public health officials, correctional
officials, and food suppliers can work together for food safety. Clearer
jurisdiction over regulation of correctional food services is needed.
PMID- 28520483
TI - Effect of the Affordable Care Act on Disparities in Breastfeeding: The Case of
Maine.
AB - OBJECTIVES: To evaluate the Affordable Care Act (ACA) breastfeeding provision and
test whether changes in coverage affected women differently according to health
insurance status. METHODS: We used the All-Payer Claims Database from Maine (2012
2014) to compare health insurance claims for lactation classes and breast pumps
between women with private insurance and women with Medicaid (1) before the ACA
breastfeeding provision, (2) after the provision came into effect, and (3) after
health insurance expansion through the Marketplace. RESULTS: We found limited
change in claims for lactation classes over the study period. By contrast, the
number of claims for breast pumps among women with private insurance increased
from 70 claims in the third quarter of 2012 to 629 claims 1 year later and 803
claims in the third quarter of 2014. Women with Medicaid had only 11 claims for
breast pumps over the entire study period. CONCLUSIONS: This 11-fold rise in
claims for breast pumps by women with private insurance suggests that these women
will likely increase breastfeeding initiation or duration; however, without
additional support for women with Medicaid, disparities in breastfeeding may
increase.
PMID- 28520485
TI - Consumption of Carbonated Soft Drinks Among Young Adolescents Aged 12 to 15 Years
in 53 Low- and Middle-Income Countries.
AB - OBJECTIVES: To compare consumption of carbonated soft drinks among young
adolescents in 53 low- and middle-income countries (LMICs). METHODS: We used 2009
to 2013 Global School-based Student Health Survey data to assess 137 449 young
adolescents aged 12 to 15 years with available data (via a standardized
questionnaire) on frequency of carbonated soft drink consumption. RESULTS:
Overall, young adolescents reported having consumed carbonated soft drinks 1.39
times per day (95% confidence interval [CI] = 1.26, 1.51), and 54.3% of
adolescents reported consuming a carbonated soft drink at least once per day.
Frequency (times per day) varied greatly across countries, ranging from 0.52 (95%
CI = 0.43, 0.60) in Kiribati to 2.39 (95% CI = 2.25, 2.53) in Suriname.
CONCLUSIONS: Our data confirm that consumption of carbonated soft drinks is
frequent among young adolescents in LMICs. Our findings highlight the need for
interventions in these countries to reduce adolescents' carbonated soft drink
consumption.
PMID- 28520486
TI - Trends in School-Related Victimization of Lesbian, Gay, and Bisexual Youths
Massachusetts, 1995-2015.
AB - OBJECTIVES: To compare changes over time in prevalence of school victimization
among lesbian, gay, and bisexual (LGB) students compared with heterosexual
students. METHODS: We analyzed data from 11 Youth Risk Behavior Surveys conducted
among representative samples of students in grades 9 through 12 in Massachusetts
during 1995 to 2015. We used multivariable logistic regression models to identify
trends over time by sexual identity. RESULTS: During 1995 to 2015, the prevalence
of missing school decreased overall (from 5.6% to 4.8%) and among heterosexual
(from 4.3% to 3.8%) and LGB (from 25.0% to 13.4%) students. The prevalence of
having been threatened decreased overall (from 7.8% to 4.1%) and among
heterosexual (from 6.5% to 3.5%) and LGB (from 32.9% to 6.7%) students.
CONCLUSIONS: We identified evidence of a significant decrease in victimization
among all students regardless of sexual identity and a steep decline among LGB
students. Additional actions to improve school climate may help eliminate the
disparities and decrease victimization for all youths.
PMID- 28520484
TI - Fe en Accion: Promoting Physical Activity Among Churchgoing Latinas.
AB - OBJECTIVES: To evaluate the impact of a faith-based intervention to promote
physical activity in Latinas. METHODS: We randomized 16 churches in San Diego
County, California, to a physical activity intervention or cancer screening
comparison condition (n = 436). The intervention followed an ecological framework
and involved promotoras. We examined 12-month intervention effects, including
accelerometer-based moderate-to-vigorous physical activity (MVPA; primary
outcome) and secondary outcomes. We conducted the study from 2010 to 2016.
RESULTS: Mixed effects analyses showed significant increases in accelerometer
based MVPA (effect size = 0.25) and self-report leisure-time MVPA (effect size =
0.38) among Latinas in the intervention versus comparison condition. Participants
in the intervention condition had about 66% higher odds of meeting the 2008
Physical Activity Guidelines, had reduced body mass index (effect size = 0.23),
and used more behavioral strategies for engaging in physical activity (effect
size = 0.42). Program attendance was associated with increased self-reported
leisure-time MVPA and the number of motivational interviewing calls was
associated with meeting the 2008 Physical Activity Guidelines. CONCLUSIONS: A
faith-based intervention was effective in increasing MVPA and decreasing body
mass index among participants. Process analyses showed the value of program
attendance and motivational interviewing calls.
PMID- 28520480
TI - Review of Recent Methodological Developments in Group-Randomized Trials: Part 2
Analysis.
AB - In 2004, Murray et al. reviewed methodological developments in the design and
analysis of group-randomized trials (GRTs). We have updated that review with
developments in analysis of the past 13 years, with a companion article to focus
on developments in design. We discuss developments in the topics of the earlier
review (e.g., methods for parallel-arm GRTs, individually randomized group
treatment trials, and missing data) and in new topics, including methods to
account for multiple-level clustering and alternative estimation methods (e.g.,
augmented generalized estimating equations, targeted maximum likelihood, and
quadratic inference functions). In addition, we describe developments in analysis
of alternative group designs (including stepped-wedge GRTs, network-randomized
trials, and pseudocluster randomized trials), which require clustering to be
accounted for in their design and analysis.
PMID- 28520487
TI - Chemical Risk Assessment: Traditional vs Public Health Perspectives.
AB - Preventing adverse health effects of environmental chemical exposure is
fundamental to protecting individual and public health. When done efficiently and
properly, chemical risk assessment enables risk management actions that minimize
the incidence and effects of environmentally induced diseases related to chemical
exposure. However, traditional chemical risk assessment is faced with multiple
challenges with respect to predicting and preventing disease in human
populations, and epidemiological studies increasingly report observations of
adverse health effects at exposure levels predicted from animal studies to be
safe for humans. This discordance reinforces concerns about the adequacy of
contemporary risk assessment practices for protecting public health. It is
becoming clear that to protect public health more effectively, future risk
assessments will need to use the full range of available data, draw on innovative
methods to integrate diverse data streams, and consider health endpoints that
also reflect the range of subtle effects and morbidities observed in human
populations. Considering these factors, there is a need to reframe chemical risk
assessment to be more clearly aligned with the public health goal of minimizing
environmental exposures associated with disease.
PMID- 28520488
TI - Firearm Legislation and Fatal Police Shootings in the United States.
AB - OBJECTIVES: To examine whether stricter firearm legislation is associated with
rates of fatal police shootings. METHODS: We used a cross-sectional, state-level
design to evaluate the effect of state-level firearm legislation on rates of
fatal police shootings from January 1, 2015, through October 31, 2016. We
measured state-level variation in firearm laws with legislative scorecards from
the Brady Center, and for fatal police shootings we used The Counted, an online
database maintained by The Guardian. RESULTS: State-level firearm legislation was
significantly associated with lower rates of fatal police shootings (incidence
rate ratio = 0.961; 95% confidence interval = 0.939, 0.984). When we controlled
for sociodemographic factors, states in the top quartile of legislative strength
had a 51% lower incidence rate than did states in the lowest quartile. Laws aimed
at strengthening background checks, promoting safe storage, and reducing gun
trafficking were associated with fewer fatal police shootings. CONCLUSIONS:
Legislative restrictions on firearms are associated with reductions in fatal
police shootings. Public Health Implications. Although further research is
necessary to determine causality and potential mechanisms, firearm legislation is
a potential policy solution for reducing fatal police shootings in the United
States.
PMID- 28520489
TI - Impact of the 2016 Ecuador Earthquake on Zika Virus Cases.
AB - OBJECTIVES: To evaluate the impact of the April 2016 7.8-magnitude earthquake in
Ecuador on the incidence of Zika virus (ZIKV) cases. METHODS: We used the
national public health surveillance system for reportable transmissible
conditions and included suspected and laboratory-confirmed ZIKV cases. We
compared the number of cases before and after the earthquake in areas closer to
and farther from the epicenter. RESULTS: From January to July 2016, 2234 patients
suspected of having ZIKV infection were reported in both affected and control
areas. A total of 1110 patients had a reverse transcription-polymerase chain
reaction assay, and 159 were positive for ZIKV. The cumulative incidence of ZIKV
in the affected area was 11.1 per 100 000 after the earthquake. The odds ratio of
having ZIKV infection in those living in the affected area was 8.0 (95% CI = 4.4,
14.6; P < .01) compared with the control area and adjusted for age, gender,
province population, and number of government health care facilities.
CONCLUSIONS: A spike in ZIKV cases occurred after the earthquake. Patients in the
area closest to the epicenter had a delay in seeking care.
PMID- 28520490
TI - Disparities in Disability by Educational Attainment Across US States.
AB - OBJECTIVES: To examine how disparities in adult disability by educational
attainment vary across US states. METHODS: We used the nationally representative
data of more than 6 million adults aged 45 to 89 years in the 2010-2014 American
Community Survey. We defined disability as difficulty with activities of daily
living. We categorized education as low (less than high school), mid (high school
or some college), or high (bachelor's or higher). We estimated age-standardized
disability prevalence by educational attainment and state. We assessed whether
the variation in disability across states occurs primarily among low-educated
adults and whether it reflects the socioeconomic resources of low-educated adults
and their surrounding contexts. RESULTS: Disparities in disability by education
vary markedly across states-from a 20 percentage point disparity in Massachusetts
to a 12-point disparity in Wyoming. Disparities vary across states mainly because
the prevalence of disability among low-educated adults varies across states.
Personal and contextual socioeconomic resources of low-educated adults account
for 29% of the variation. CONCLUSIONS: Efforts to reduce disparities in
disability by education should consider state and local strategies that reduce
poverty among low-educated adults and their surrounding contexts.
PMID- 28520491
TI - Firearm-Related Laws in All 50 US States, 1991-2016.
AB - OBJECTIVES: To describe a new database containing detailed annual information on
firearm-related laws in place in each of the 50 US states from 1991 to 2016 and
to summarize key trends in firearm-related laws during this time period. METHODS:
Using Thomson Reuters Westlaw data to access historical state statutes and
session laws, we developed a database indicating the presence or absence of each
of 133 provisions of firearm laws in each state over the 26-year period. These
provisions covered 14 aspects of state policies, including regulation of the
process by which firearm transfers take place, ammunition, firearm possession,
firearm storage, firearm trafficking, and liability of firearm manufacturers.
RESULTS: An examination of trends in state firearm laws via this database
revealed that although the number of laws nearly doubled during the study period,
there was substantial heterogeneity across states, leading to a widening
disparity in the number of firearm laws. CONCLUSIONS: This database can help
advance firearm policy research by providing 26 years of comprehensive policy
data that will allow longitudinal panel study designs that minimize the
limitations present in many previous studies.
PMID- 28520492
TI - Use of a Digital Health Application for Influenza Surveillance in China.
AB - OBJECTIVES: To examine whether a commercial digital health application could
support influenza surveillance in China. METHODS: We retrieved data from the
Thermia online and mobile educational tool, which allows parents to monitor their
children's fever and infectious febrile illnesses including influenza. We modeled
monthly aggregated influenza-like illness case counts from Thermia users over
time and compared them against influenza monthly case counts obtained from the
National Health and Family Planning Commission of the People's Republic of China
by using time series regression analysis. We retrieved 44 999 observations from
January 2014 through July 2016 from Thermia China. RESULTS: Thermia appeared to
predict influenza outbreaks 1 month earlier than the National Health and Family
Planning Commission influenza surveillance system (P = .046). Being younger, not
having up-to-date immunizations, and having an underlying health condition were
associated with participant-reported influenza-like illness. CONCLUSIONS: Digital
health applications could supplement traditional influenza surveillance systems
in China by providing access to consumers' symptom reporting. Growing popularity
and use of commercial digital health applications in China potentially affords
opportunities to support disease detection and monitoring and rapid treatment
mobilization.
PMID- 28520493
TI - Increasing Walking in the Hartsfield-Jackson Atlanta International Airport: The
Walk to Fly Study.
AB - OBJECTIVES: To test the effectiveness of a point-of-decision intervention to
prompt walking, versus motorized transport, in a large metropolitan airport.
METHODS: We installed point-of-decision prompt signage at 4 locations in the
airport transportation mall at Hartsfield-Jackson Atlanta International Airport
(Atlanta, GA) at the connecting corridor between airport concourses. Six ceiling
mounted infrared sensors counted travelers entering and exiting the study
location. We collected traveler counts from June 2013 to May 2016 when
construction was present and absent (preintervention period: June 2013-September
2014; postintervention period: September 2014-May 2016). We used a model that
incorporated weekly walking variation to estimate the intervention effect on
walking. RESULTS: There was an 11.0% to 16.7% relative increase in walking in the
absence of airport construction where 580 to 810 more travelers per day chose to
walk. Through May 2016, travelers completed 390 000 additional walking trips.
CONCLUSIONS: The Walk to Fly study demonstrated a significant and sustained
increase in the number of airport travelers choosing to walk. Providing signage
about options to walk in busy locations where reasonable walking options are
available may improve population levels of physical activity and therefore
improve public health.
PMID- 28520494
TI - Racial/Ethnic Disparities at the End of an HIV Epidemic: Persons Who Inject Drugs
in New York City, 2011-2015.
AB - OBJECTIVES: To examine whether racial/ethnic disparities persist at the "end of
the HIV epidemic" (prevalence of untreated HIV infection < 5%; HIV incidence <
0.5 per 100 person-years) among persons who inject drugs (PWID) in New York City.
METHODS: We recruited 2404 PWID entering New York City substance use treatment in
2001 to 2005 and 2011 to 2015. We conducted a structured interview, and testing
for HIV and herpes simplex virus 2 (HSV-2; a biomarker for high sexual risk). We
estimated incidence by using newly diagnosed cases of HIV. Disparity analyses
compared HIV, untreated HIV, HIV-HSV-2 coinfection, HIV monoinfection, and
estimated HIV incidence among Whites, African Americans, and Latinos. RESULTS: By
2011 to 2015, Whites, African Americans, and Latino/as met both criteria of our
operational "end-of-the-epidemic" definition. All comparisons that included HIV
HSV-2-coinfected persons had statistically significant higher rates of HIV among
racial/ethnic minorities. No comparisons limited to HIV monoinfected persons were
significant. CONCLUSIONS: "End-of-the-epidemic" criteria were met among White,
African American, and Latino/a PWID in New York City, but elimination of
disparities may require a greater focus on PWID with high sexual risk.
PMID- 28520496
TI - Shelter-Based Opioid Treatment: Increasing Access to Addiction Treatment in a
Family Shelter.
PMID- 28520495
TI - An Approach to Assess the Burden of Work-Related Injury, Disease, and Distress.
AB - The true burden (morbidity, mortality, disability, cost, pain, distress) of
occupational and work-related diseases and injuries is unknown, and what is
reported as burden is significantly underestimated. This underestimation affects
the way decision-makers view investments in research and worker protection, which
in turn has a substantial impact on national welfare and public health. To better
describe the societal and individual burdens of occupational and work-related
diseases and injuries, we propose an approach to gauge what is known about burden
and where new assessments may be made. This approach consists of 4 elements to
consider in burden assessments: (1) utilizing multiple domains, including the
individual worker, the worker's family, the community in which the workplace is
located, the employer, and society as a whole; (2) taking a broader view of the
work-relatedness of disease and injury; (3) assessing the impact of the entire
working-life continuum; and (4) applying the comprehensive concept of "well
being" as an indicator in addressing contemporary changes in the nature of work,
the workplace, and the workforce. Further research on burden and enhanced
surveillance is needed to develop these elements.
PMID- 28520497
TI - LncRNA PVT1 Regulates Chondrocyte Apoptosis in Osteoarthritis by Acting as a
Sponge for miR-488-3p.
AB - Long noncoding RNAs (lncRNAs) have been known to be involved in multiple diverse
diseases, including osteoarthritis (OA). The present study aims at exploring the
biological role of lncRNA plasmacytoma variant translocation 1 (PVT1) in OA and
the underlying mechanism. Results showed that the expression of PVT1 was
upregulated in OA chondrocytes compared with normal chondrocytes, silencing PVT1
inhibited the apoptosis of OA chondrocytes, and overexpression of PVT1 promoted
the apoptosis of normal chondrocytes. To further investigate the underlying
mechanism, miR-488-3p was predicted to be a targeted microRNA of PVT1. Different
methods, including MS2 RNA immunoprecipitation (RIP), luciferase activity, and
anti-AGO2 RIP, were performed to detect the interaction between PVT1 and miR-488
3p, which suggested that PVT1 negatively regulated miR-488-3p in OA chondrocytes.
Moreover, PVT1 promoted the apoptosis of OA and normal chondrocytes through miR
488-3p. Collectively, this study revealed that lncRNA PVT1 regulated the
apoptosis of chondrocytes by acting as a sponge for miR-488-3p in OA. PVT1 may be
considered a new therapeutic target for the treatment of OA.
PMID- 28520498
TI - Palliative Care and Parkinson's Disease: Caregiver Perspectives.
AB - BACKGROUND: Palliative care for Parkinson's disease (PD) is an emerging area of
interest for clinicians, patients and families. Identifying the palliative care
needs of caregivers is central to developing and implementing palliative services
for families affected by PD. The objective of this paper was to elicit PD
caregiver needs, salient concerns, and preferences for care using a palliative
care framework. MATERIALS AND METHODS: 11 PD caregivers and one non-overlapping
focus group (n = 4) recruited from an academic medical center and community
support groups participated in qualitative semi-structured interviews. Interviews
and focus group discussion were digitally recorded, transcribed and entered into
ATLAS.ti for coding and analysis. We used inductive qualitative data analysis
techniques to interpret responses. RESULTS: Caregivers desired access to
emotional support and education regarding the course of PD, how to handle
emergent situations (e.g. falls and psychosis) and medications. Participants
discussed the immediate impact of motor and non-motor symptoms as well as
concerns about the future, including: finances, living situation, and caretaking
challenges in advanced disease. Caregivers commented on the impact of PD on their
social life and communication issues between themselves and patient. All
participants expressed interest and openness to multidisciplinary approaches for
addressing these needs. CONCLUSIONS: Caregivers of PD patients have considerable
needs that may be met through a palliative care approach. Caregivers were
receptive to the idea of multidisciplinary care in order to meet these needs.
Future research efforts are needed to develop and test the clinical and cost
effectiveness of palliative services for PD caregivers.
PMID- 28520500
TI - Tracey.
PMID- 28520499
TI - Genome-Wide Identification of Potential Drug Target in Enterobacteriaceae Family:
A Homology-Based Method.
AB - The Enterobacteriaceae is a large family of Gram-negative, facultative anaerobic,
non-spore forming rod-shaped bacteria that includes harmless and pathogenic
organisms. The emergence and development of drug resistance in Enterobacteriaceae
is complicating the treatment of serious infections. The aim of this study is to
predict and characterize putative drug targets in Enterobacteriaceae family
employing a homology-based computational method. The final putative drug targets
were qualitatively characterized via cellular function prediction, subcellular
localization prediction, broad-spectrum, and druggability analyses. Of 6,327
analyzed proteins, 35 proteins were selected as final putative drug targets in
Enterobacteriaceae family. These putative drug targets were involved in different
vital pathways like metabolism, biosynthesis of macromolecule, and cell division.
Predicted drug targets were also localized in the cytoplasm and cytoplasmic
membrane of the pathogen that acts as antimicrobial or vaccine targets. Of 35
drug targets, 5 targets were druggable and 30 targets were not druggable and were
predicted as novel drug targets, which should be further evaluated to develop new
antimicrobial. Thirteen drug targets were considered as broad-spectrum targets.
It is expected that results of our study could facilitate the production of novel
antibacterial for efficient treatment of infections caused by Enterobacteriaceae
pathogens.
PMID- 28520501
TI - Molecular Characterization of Multidrug-Resistant Escherichia coli Isolates from
Bovine Clinical Mastitis and Pigs in the Vojvodina Province, Serbia.
AB - The aim of the study was to characterize multidrug-resistant (MDR) Escherichia
coli isolates collected in Serbia from bovine clinical mastitis cases and
diseased pigs, mainly with molecular methods. A total of 48 E. coli isolates was
collected during the years 2013-2014, of which 22 were MDR and were included in
further analysis. Phylogenetic typing showed that 17 isolates belonged to group
A, while two isolates were classified in group B1 and a single one in group D.
All isolates showed unique macrorestriction patterns. Phenotypic susceptibility
testing revealed resistances of the isolates against up to 13 antimicrobial
agents, including resistance to fluoroquinolones. A wide variety of resistance
genes was detected by PCR amplification and sequencing of amplicons. Sequence
analysis of the quinolone resistance determining regions of topoisomerase genes
revealed mutations in gyrA, parC, and/or parE. Plasmid-mediated quinolone
resistance genes were detected in two porcine (aac-6'-Ib-cr and qnrS,
respectively) isolates and a single bovine (aac-6'-Ib-cr) isolate. Resistance
genes were found to be located on conjugative plasmids in 16 cases, many of which
conferred a multidrug resistance phenotype. In conclusion, the plentitude of
resistance genes located on conjugative plasmids and integrons in E. coli from
cows and pigs in Vojvodina, Serbia, pose a high risk for horizontal gene transfer
in bacteria from livestock husbandry.
PMID- 28520502
TI - End-of-Life Care for Patients with Schizophrenia #332.
PMID- 28520504
TI - Hope and Uncertainty in the Age of Miracles.
PMID- 28520503
TI - Serum Alanine Aminotransferase Trends and Their Relationship with Obesity and
Metabolic Syndrome in United States Adolescents, 1999-2014.
AB - INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD), characterized by
hepatocyte dysfunction, fat accumulation, and fibrosis, is the most common cause
of chronic liver disease in children. Elevated levels of serum alanine
aminotransferase (ALT) are used clinically to identify potential liver
dysfunction. Our goal was to assess for changes in the national prevalence of
elevated ALT over time and potential relationship to trends in the metabolic
syndrome (MetS) severity and elevated body mass index (BMI). MATERIALS AND
METHODS: We studied 5411 non-Hispanic white, non-Hispanic black, and Hispanic
adolescents aged 12-19 with complete MetS Z-score and ALT data from the National
Health and Nutrition Examination Survey 1999-2014. Elevated ALT levels were
defined by two different cutoffs: one for both sexes (30 U/L) and another that
was sex specific (22 U/L girls; 25 U/L boys). MetS severity was assessed using a
sex- and race-/ethnicity-specific MetS Z-score. RESULTS: We did not find a
statistically significant linear increase in either mean ALT or the prevalence of
elevated ALT differed over time. As expected, ALT levels were significantly
correlated with BMI Z-score and MetS Z-score (P < 0.0001). Over time, BMI Z
scores increased and MetS severity Z-score decreased. CONCLUSION: Prevalence of
elevated ALT did not exhibit a linear change between 1999 and 2014 in U.S.
adolescents, potentially due to divergent trends regarding BMI and MetS severity.
Continued vigilance in monitoring BMI and ALT levels is advised for the U.S.
adolescent population. MetS Z-score could act as an additional tool to monitor
risk of elevated ALT and subsequent development of NAFLD.
PMID- 28520505
TI - Early Blockade of Matrix Metalloproteinases in Spinal-Cord-Injured Dogs Results
in a Long-Term Increase in Bladder Compliance.
AB - Spinal cord injury (SCI) is often accompanied by reduced bladder compliance,
which contributes to adverse conditions including urinary tract infections and
vesicoureteral reflux. Reduced compliance is, in part, attributed to extensive
remodeling of the bladder wall, including the extracellular matrix (ECM). Here,
we tested the hypothesis that blockade of matrix metalloproteinases (MMPs), known
for their ability to remodel the ECM, improves bladder compliance in dogs with
SCI. We first evaluated dogs with naturally occurring SCIs resulting from
intervertebral disc herniation (IVDH). After characterizing the natural history
of urological recovery by cystometry in healthy dogs (n = 10) and dogs with SCIs
(n = 20), we conducted a randomized, double-blinded, placebo-controlled clinical
trial in dogs with IVDH-associated SCIs to assess the efficacy of the broad
spectrum MMP inhibitor, GM6001, given within 48 h post-injury. The primary
outcomes were bladder compliance, as measured by cystometry, and an ordinal gait
score (Texas Spinal Cord Injury Score; TSCIS) at day 42 post-SCI. Dogs (n = 93)
were randomized to receive either dimethyl sulfoxide (DMSO) or GM6001+DMSO. There
were transient, but significantly (p = 0.023) greater, adverse events (31 of 42;
74%) in the GM6001-treated group relative to vehicle controls (22 of 46; 48%).
Whereas there were no differences in TSCIS between treatment groups at day 42 (p
= 0.9679), bladder compliance was significantly higher in dogs treated with
GM6001+DMSO compared to controls (p = 0.0272). Further studies are needed to
determine whether this inhibition results from a direct interaction with the
bladder wall or indirectly through neural-based mechanisms.
PMID- 28520506
TI - Urinary nanovesicles captured by lectins or antibodies demonstrate variations in
size and surface glycosylation profile.
AB - AIM: The use of carbohydrate-binding proteins (lectins) to isolate urinary
extracellular vesicles (uEVs) was investigated and the captured subpopulations
were characterized. METHODS: Pooled uEVs from multiple healthy donors were
exposed to lectin-conjugated or antibody-conjugated beads. Recovered uEVs were
evaluated by protein estimation, transmission electron microscopy, nanoparticle
tracking analysis and lectin microarray profiling. RESULTS: uEVs isolated by
lectin- and antibody-based affinity capture exhibited distinct variations in size
and surface content. Transmission electron microscopy confirmed similar EV
diameters to those established by nanoparticle tracking analysis, but total
particle counts did not correlate closely with protein-based quantification.
Lectin microarray profiling demonstrated capture-dependent differences in surface
glycosylation. CONCLUSION: Selective, carbohydrate-mediated EV isolation by
lectin affinity approaches may prove immediately useful for research and find
eventual use in clinical applications.
PMID- 28520507
TI - Gold nanoparticles enhance the differentiation of embryonic stem cells into
dopaminergic neurons via mTOR/p70S6K pathway.
AB - AIM: This study aimed to investigate the effect of gold nanoparticles (AuNPs) on
differentiation of mouse embryonic stem cells (ESCs) into dopaminergic (DA)
neurons and explore the possible underlying molecular mechanisms. MATERIALS &
METHODS: The efficiency of AuNPs on DA neuron differentiation was evaluated by
observing fluorescence in TH promoter-engineered GFP-reporter ESCs, western blot
and real-time PCR. The possible signal pathway was determined by western blot.
RESULTS: Compared with feeder-free control condition, AuNPs are able to enhance
fate specification of ESCs into DA neurons. Moreover, mTOR/p70S6K signaling
pathway was found involving in this AuNPs-mediated DA neuron differentiation.
CONCLUSION: Our findings may lead future insight investigation into the
underlying mechanisms and potential application of AuNPs in stem cell research.
PMID- 28520510
TI - Abstracts from The Aerosol Society Drug Delivery to the Lungs 27 Edinburgh
International Conference Centre Edinburgh, Scotland, UK December 7-9, 2016.
PMID- 28520509
TI - Recent advances in electrospun nanofibers for wound healing.
AB - Electrospun nanofibers represent a novel class of materials that show great
potential in many biomedical applications including biosensing, regenerative
medicine, tissue engineering, drug delivery and wound healing. In this work, we
review recent advances in electrospun nanofibers for wound healing. This article
begins with a brief introduction on the wound, and then discusses the unique
features of electrospun nanofibers critical for wound healing. It further
highlights recent studies that have used electrospun nanofibers for wound healing
applications and devices, including sutures, multifunctional dressings, dermal
substitutes, engineered epidermis and full-thickness skin regeneration. Finally,
we finish with conclusions and future perspective in this field.
PMID- 28520512
TI - Zein nanoparticles as vehicles for oral delivery purposes.
PMID- 28520511
TI - Upregulation of AcrEF in Quinolone Resistance Development in Escherichia coli
When AcrAB-TolC Function Is Impaired.
AB - We studied mechanisms of drug resistance development in Escherichia coli strains
lacking efflux pump components. E. coli K12 deletion mutants were subjected to
increasing concentrations of ciprofloxacin (CIP) to determine the frequency of
target gene mutations. We generated a series of mutants that were selected based
on their minimum inhibitory concentrations (MICs) to CIP, as well as their
corresponding point mutations in target genes. The mutants displayed a number of
target modifications and, in particular, gyrA mutations altering codons Ser83Leu,
Asp87Gly, and Asp87His as well as a change in parC at 78 (substitution of Gly for
Asp). All these mutations were related to drug resistance. When exposed to CIP,
mutants lacking efflux pump genes acrA and acrB demonstrated a low level of
resistance that was because of point mutations in the target genes. High-level
resistance was achieved with a 100- to 500-fold increase in expression of efflux
pump genes acrE and acrF that compensated for the loss of AcrA and AcrB, and thus
resulted in an obvious increase of CIP MIC. We demonstrate that an intact AcrAB
TolC efflux pump is crucial to the development of bacterial resistance. Its
activity is complemented by expression of the alternative AcrEF efflux pump.
PMID- 28520513
TI - Rectal Mucinous Adenocarcinoma: MR Imaging Assessment of Response to Concurrent
Chemotherapy and Radiation Therapy-A Hypothesis-generating Study.
AB - Purpose To develop a system for assessment of tumor regression grade (TRG) with
magnetic resonance (MR) imaging that is applicable to rectal mucinous
adenocarcinoma (RMAC) and to obtain a preliminary evaluation of the association
of MR imaging assessment of TRG with response to preoperative concurrent
chemotherapy and radiation therapy (CCRT). Materials and Methods This
retrospective study was approved by the institutional review board, and informed
consent was waived. Pre- and post-CCRT MR images of 59 patients with RMAC (median
age, 59 years; range, 29-80 years; 42 men [median age, 59 years; range, 36-80
years] and 17 women [median age, 57 years; range, 29-79 years]) who underwent
CCRT and subsequent elective resection from July 2005 to June 2015 were analyzed.
Two experienced gastrointestinal radiologists independently analyzed imaging
parameters such as T stage, mesorectal fascia status, extramural vascular
invasion status, and TRG by using modified criteria developed for assessment of
RMAC. Interobserver variability was calculated with weighted kappa analysis, and
disagreement was settled in consensus. MR imaging TRG results were compared with
those from pathologic TRG analysis (Mandard grade). Logistic regression analyses
were performed to evaluate associations between imaging parameters and pathologic
TRG. Results There was moderate to substantial agreement for imaging parameters
(post-CCRT T stage-weighted kappa, 0.7134; post-CCRT mesorectal fascia status,
0.618; TRG, 0.5023). Modified MR imaging TRG results were significantly
associated with pathologic responsiveness (responsive group, Mandard grade 1 or
2; nonresponsive group, Mandard grades 3-5; P = .023). Results of univariate and
multivariate logistic regression analyses indicated that MR imaging TRG was the
only factor significantly associated with CCRT responsiveness (univariate
analysis, P = .023; multivariate analysis, P = .0261). Conclusion The modified MR
imaging assessment of TRG was associated with treatment response to CCRT in
patients with RMAC. (c) RSNA, 2017 Online supplemental material is available for
this article.
PMID- 28520514
TI - Flea and Small Mammal Species Composition in Mixed-Grass Prairies: Implications
for the Maintenance of Yersinia pestis.
AB - Maintenance of sylvatic plague in prairie dogs (Cynomis spp.) was once thought
unlikely due to high mortality rates; yet more recent findings indicate that low
level enzootic plague may be maintained in susceptible prairie dog populations.
Another hypothesis for the maintenance of sylvatic plague involves small mammals,
other than prairie dogs, as an alternative reservoir in the sylvatic plague
system. These hypotheses, however, are not mutually exclusive, as both prairie
dogs and small mammals could together be driving sylvatic cycles of plague. The
concept of a bridging vector has been used to explain the transmission of
pathogens from one host species to another. In the case of sylvatic plague, this
would require overlap in fleas between small mammals and prairie dogs, and
potentially other species such as carnivores. Our goal was to evaluate the level
of flea sharing between black-tailed prairie dogs (Cynomis ludovicianus) and
other small mammals in a mixed-grass prairie in South Dakota. We investigated the
species richness of small mammals and small-mammal fleas in a mixed-grass prairie
system and compared findings with previous studies from a short-grass ecosystem
in Colorado. Over the summer field seasons 2014-2016 we live-trapped small
mammals, collected fleas, and showed differences between both the flea and small
mammal composition of the two systems. We also recorded higher densities of deer
mice and lower densities of northern grasshopper mice in mixed versus shortgrass
prairies. We confirmed, as is the case in shortgrass prairies, a lack of
substantial flea species overlap on small mammal hosts and fleas from prairie
dogs and their burrows. Moreover this study demonstrates that although small
mammals may not play a large part in interepizootic plague cycling in shortgrass
prairie ecosystems, their role in mixed-grass prairies requires further
evaluation.
PMID- 28520515
TI - Overcoming the tumor microenvironment: the role of nanohyperthermia.
PMID- 28520517
TI - Nanoantibiotics: a new paradigm for the treatment of surgical infection.
AB - Infections following orthopedic device implantations often impose a substantial
health burden and result in high medical costs. Currently, preventative methods
are often employed following an orthopedic implant to reduce risk of infection;
however, contamination of the surgical site can still occur. Although antibiotics
have demonstrated a substantial reduction in bacterial growth and maintenance,
biofilm formation around the implant can often minimize efficacy of the
antibiotic. Recently, nanotechnology has garnered significant interest, resulting
in the development of several antibiotic delivery strategies that exhibit
extended release and increased efficacy. In this review, treatment methods of
orthopedic-device-related infections will be discussed and an overview of
antimicrobial-based nanotechnologies will be provided. Specifically, nonmetal-,
metal- and oxide-based nanotechnologies, incorporating antibacterial strategies,
will be discussed.
PMID- 28520516
TI - Mesenchymal Stem Cell Migration and Proliferation Are Mediated by Hypoxia
Inducible Factor-1alpha Upstream of Notch and SUMO Pathways.
AB - Mesenchymal stem cells (MSCs) are effective in treating several pathologies. We
and others have demonstrated that hypoxia or hypoxia-inducible factor 1 alpha
(HIF-1alpha) stabilization improves several MSC functions, including cell
adhesion, migration, and proliferation, thereby increasing their therapeutic
potential. To further explore the mechanisms induced by HIF-1alpha in MSCs, we
studied its relationship with Notch signaling and observed that overexpression of
HIF-1alpha in MSCs increased protein levels of the Notch ligands Jagged 1-2 and
Delta-like (Dll)1, Dll3, and Dll4 and potentiated Notch signaling only when this
pathway was activated. Crosstalk between HIF and Notch resulted in Notch
dependent migration and spreading of MSCs, which was abolished by gamma-secretase
inhibition. However, the HIF-1-induced increase in MSC proliferation was
independent of Notch signaling. The ubiquitin family member, small ubiquitin-like
modifier (SUMO), has important functions in many cellular processes and increased
SUMO1 protein levels have been reported in hypoxia. To investigate the potential
involvement of SUMOylation in HIF/Notch crosstalk, we measured general
SUMOylation levels and observed increased SUMOylation in HIF-1-expressing MSCs.
Moreover, proliferation and migration of MSCs were reduced in the presence of a
SUMOylation inhibitor, and this effect was particularly robust in HIF-MSCs.
Immunoprecipitation studies demonstrated SUMOylation of the intracellular domain
of Notch1 (N1ICD) in HIF-1-expressing MSCs, which contributed to Notch pathway
activation and resulted in increased levels of N1ICD nuclear translocation as
assessed by subcellular fractionation. SUMOylation of N1ICD was also observed in
HEK293T cells with stabilized HIF-1alpha expression, suggesting that this is a
common mechanism in eukaryotic cells. In summary, we describe, for the first
time, SUMOylation of N1ICD, which is potentiated by HIF signaling. These
phenomena could be relevant for the therapeutic effects of MSCs in hypoxia or
under conditions of HIF stabilization.
PMID- 28520518
TI - Arrested Development: Infantile Hemangioma and the Stem Cell Teratogenic
Hypothesis.
AB - BACKGROUND: Early-life programming is defined by the adaptive changes made by the
fetus in response to an adverse in utero environment. Infantile hemangioma (IH),
a vascular anomaly, is the most common tumor of infancy. Here we take IH as the
tumor model to propose the stem cell teratogenic hypothesis of tumorigenesis and
the potential involvement of the immune system. OBJECTIVES: Teratogenic agents
include chemicals, heavy metals, pathogens, and ionizing radiation. To
investigate the etiology and pathogenesis of IH, we hypothesized that they result
from a teratogenic mechanism. Immature, incompletely differentiated, dysregulated
progenitor cells (multipotential stem cells) are arrested in development with
vasculogenic, angiogenic, and tumorigenic potential due to exposure to
teratogenic agents such as extrinsic factors that disrupt intrinsic factors via
molecular mimicry. During the critical period of immunological tolerance,
environmental exposure to immunotoxic agents may harness the teratogenic
potential in the developing embryo or fetus and modify the early-life programming
algorithm by altering normal fetal development, causing malformations, and
inducing tumorigenesis. Specifically, exposure to environmental agents may
interfere with physiological signaling pathways and contribute to the generation
of IH, by several mechanisms. DISCUSSION: An adverse in utero environment no
longer serves as a sustainable environment for proper embryogenesis and normal
development. Targeted disruption of stem cells by extrinsic factors can alter the
genetic program. CONCLUSIONS: This article offers new perspectives to stimulate
discussion, explore novel experimental approaches (such as
immunotoxicity/vasculotoxicity assays and novel isogenic models), and to address
the questions raised to convert the hypotheses into nontoxic, noninvasive
treatments.
PMID- 28520520
TI - Three-Dimensional Cell Culture: A Rapidly Emerging Approach to Cellular Science
and Drug Discovery.
PMID- 28520523
TI - Making N-of-1 Medicine a Reality.
PMID- 28520519
TI - Oil-Based or Water-Based Contrast for Hysterosalpingography in Infertile Women.
AB - BACKGROUND: Pregnancy rates among infertile women have been reported to increase
after hysterosalpingography, but it is unclear whether the type of contrast
medium used (oil-based or water-soluble contrast) influences this potential
therapeutic effect. METHODS: We performed a multicenter, randomized trial in 27
hospitals in the Netherlands in which infertile women who were undergoing
hysterosalpingography were randomly assigned to undergo this procedure with the
use of oil-based or water-based contrast. Subsequently, couples received
expectant management or the women underwent intrauterine insemination. The
primary outcome was ongoing pregnancy within 6 months after randomization.
Outcomes were analyzed according to the intention-to-treat principle. RESULTS: A
total of 1119 women were randomly assigned to hysterosalpingography with oil
contrast (557 women) or water contrast (562 women). A total of 220 of 554 women
in the oil group (39.7%) and 161 of 554 women in the water group (29.1%) had an
ongoing pregnancy (rate ratio, 1.37; 95% confidence interval [CI], 1.16 to 1.61;
P<0.001), and 214 of 552 women in the oil group (38.8%) and 155 of 552 women in
the water group (28.1%) had live births (rate ratio, 1.38; 95% CI, 1.17 to 1.64;
P<0.001). Rates of adverse events were low and similar in the two groups.
CONCLUSIONS: Rates of ongoing pregnancy and live births were higher among women
who underwent hysterosalpingography with oil contrast than among women who
underwent this procedure with water contrast. (Netherlands Trial Register number,
NTR3270 .).
PMID- 28520522
TI - Perceptions of Statin Discontinuation among Patients with Life-Limiting Illness.
AB - BACKGROUND: Optimal management of chronic medications for patients with life
limiting illness is uncertain. Medication deprescribing may improve outcomes in
this population, but patient concerns regarding deprescribing are unclear.
OBJECTIVE: The aim of this study was to quantify the perceived benefits and
concerns of statin discontinuation among patients with life-limiting illness.
DESIGN: Baseline data from a multicenter, pragmatic clinical trial of statin
discontinuation were used. SETTING/SUBJECTS: Cognitively intact participants with
a life expectancy of 1-12 months receiving statin medications for primary or
secondary prevention were enrolled. MEASUREMENTS: Responses to a 9-item
questionnaire addressing patient concerns about discontinuing statins were
collected. We used Pearson chi-square tests to compare responses by primary life
limiting diagnosis (cancer, cardiovascular disease, other). RESULTS: Of 297
eligible participants, 58% had cancer, 8% had cardiovascular disease, and 30%
other primary diagnoses. Mean (standard deviation) age was 72 (11) years. Fewer
than 5% of participants expressed concern that statin deprescribing indicated
physician abandonment. About one in five participants reported being told to take
statins for the rest of their life (18%) or feeling that discontinuation
represented prior wasted effort (18%). Many participants reported benefits of
stopping statins, including spending less money on medications (63%), potentially
stopping other medications (34%), and having a better quality of life (25%). More
participants with cardiovascular disease as a primary diagnosis perceived that
quality-of-life benefits related to statin discontinuation (52%) than
participants with cancer (27%) or noncardiovascular disease diagnoses (27%) [p =
0.034]. CONCLUSION: Few participants expressed concerns about discontinuing
statins; many perceived potential benefits. Cardiovascular disease patients
perceived greater potential positive impact from statin discontinuation.
PMID- 28520525
TI - Companion and Point-of-Care Sensor System for Rapid Multiplexed Detection of a
Panel of Infectious Disease Markers.
AB - A nanochannel-based electrochemical biosensor has been demonstrated for rapid and
multiplexed detection of a panel of three biomarkers associated with rapid
detection of sepsis. The label-free biosensor detected procalcitonin (PCT),
lipoteichoic acid (LTA), and lipopolysaccharide (LPS) from human whole blood. The
biosensor comprises a nanoporous nylon membrane integrated onto a microelectrode
sensor platform for nanoconfinement effects. Charge perturbations due to
biomarker binding are recorded as impedance changes using electrochemical
impedance spectroscopy. The measured impedance change is used to quantitatively
determine the concentration of the three biomarkers using antibody receptors from
the tested sample. We were successful in detecting and quantifying the three
biomarkers from whole blood. The limit of detection was 0.1 ng/mL for PCT and 1
ug/mL for LPS and LTA. The sensor was able to demonstrate a dynamic range of
detection from 01.1 ng/mL to 10 ug/mL for PCT and from 1 ug/mL to 1000 ug/mL for
LPS and LTA biomarkers. This novel technology has promising preliminary results
toward the design of sensors for rapid and sensitive detection of the three panel
biomarkers in whole blood toward diagnosis and classification of sepsis.
PMID- 28520521
TI - Three-Dimensional Cell Cultures in Drug Discovery and Development.
AB - The past decades have witnessed significant efforts toward the development of
three-dimensional (3D) cell cultures as systems that better mimic in vivo
physiology. Today, 3D cell cultures are emerging, not only as a new tool in early
drug discovery but also as potential therapeutics to treat disease. In this
review, we assess leading 3D cell culture technologies and their impact on drug
discovery, including spheroids, organoids, scaffolds, hydrogels, organs-on-chips,
and 3D bioprinting. We also discuss the implementation of these technologies in
compound identification, screening, and development, ranging from disease
modeling to assessment of efficacy and safety profiles.
PMID- 28520528
TI - Expanding the Roster of ROS1 Inhibitors.
PMID- 28520530
TI - To Pump or Not to Pump in Pregnancy?
PMID- 28520529
TI - Synthesis of theranostic epithelial cell adhesion molecule targeted mesoporous
silica nanoparticle with gold gatekeeper for hepatocellular carcinoma.
AB - AIM: In this study, we report the fabrication of epithelial cell adhesion
molecule targeted 5-fluorouracil (5-FU) encapsulated PEGylated mesoporous silica
nanoparticles (NPs) hybridized with gold NPs (PEG-Au@Si-5-FU) as gatekeeper for
theranostic applications. MATERIALS & METHODS: The prepared targeted and
nontargeted formulations were evaluated in vitro in terms of their cellular
internalization and toxicity. The prepared theranostic hybrid system was also
implemented for computed tomography of HepG2 tumor-bearing nude mice in vivo.
RESULTS: Fluorescence microscopy and MTT assay demonstrated that the developed
epithelial cell adhesion molecule-PEG-Au@Si-5-FU had higher cytotoxicity than
nontargeted PEG-Au@Si-5-FU in 2D and 3D HepG2 cell cultures. Moreover, the
targeted hybrid system was preferentially accumulated in HepG2 tumor cells in
vitro and in vivo. CONCLUSION: This work introduces a novel strategy for
developing multimodal NPs via nanoparticulate hybrid materials.
PMID- 28520526
TI - KIR3DL1/ HL A-B Subtypes Govern Acute Myelogenous Leukemia Relapse After
Hematopoietic Cell Transplantation.
AB - Purpose Disease relapse remains a major challenge to successful outcomes in
patients who undergo allogeneic hematopoietic cell transplantation (HCT). Donor
natural killer (NK) cell alloreactivity in HCT can control leukemic relapse, but
capturing alloreactivity in HLA-matched HCT has been elusive. HLA expression on
leukemia cells-upregulated in the post-HCT environment-signals for NK cell
inhibition via inhibitory killer immunoglobulin-like (KIR) receptors and
interrupts their antitumor activity. We hypothesized that varied strengths of
inhibition among subtypes of the ubiquitous KIR3DL1 and its cognate ligand, HLA
B, would titrate NK reactivity against acute myelogenous leukemia (AML). Patients
and Methods By using an algorithm that was based on polymorphism-driven
expression levels and specificities, we predicted and tested inhibitory and
cytotoxic NK potential on the basis of KIR3DL1/HLA-B subtype combinations in
vitro and evaluated their impact in 1,328 patients with AML who underwent HCT
from 9/10 or 10/10 HLA-matched unrelated donors. Results Segregated by KIR3DL1
subtype, NK cells demonstrated reproducible patterns of strong, weak, or
noninhibition by target cells with defined HLA-B subtypes, which translated into
discrete cytotoxic hierarchies against AML. In patients, KIR3DL1 and HLA-B
subtype combinations that were predictive of weak inhibition or noninhibition
were associated with significantly lower relapse (hazard ratio [HR], 0.72; P =
.004) and overall mortality (HR, 0.84; P = .030) compared with strong inhibition
combinations. The greatest effects were evident in the high-risk group of
patients with all KIR ligands (relapse: HR, 0.54; P < .001; and mortality: HR,
0.74; P < .008). Beneficial effects of weak and noninhibiting KIR3DL1 and HLA-B
subtype combinations were separate from and additive to the benefit of donor
activating KIR2DS1. Conclusion Consideration of KIR3DL1-mediated inhibition in
donor selection for HLA-matched HCT may achieve superior graft versus leukemia
effects, lower risk for relapse, and an increase in survival among patients with
AML.
PMID- 28520531
TI - Artificial Pancreas in Young Children.
PMID- 28520527
TI - Open-Label, Multicenter, Phase II Study of Ceritinib in Patients With Non-Small
Cell Lung Cancer Harboring ROS1 Rearrangement.
AB - Purpose ROS1 rearrangement is a distinct molecular subset of non-small-cell lung
cancer (NSCLC). We investigated the efficacy and safety of ceritinib in patients
with ROS1-rearranged NSCLC. Patients and Methods We enrolled 32 patients with
advanced NSCLC who tested positive for ROS1 rearrangement by fluorescent in situ
hybridization. Ceritinib 750 mg was administered once daily. The primary end
point was objective response rate. The secondary end points were disease control
rate; duration of response; progression-free survival; overall survival;
toxicity; and concordance among fluorescent in situ hybridization,
immunohistochemistry, and next-generation sequencing. Results Between June 7,
2013, and February 1, 2016, 404 patients underwent ROS1 prescreening, and 32
patients with ROS1 rearrangement were enrolled. All patients except two were
crizotinib-naive. At the time of data cutoff, the median follow-up was 14.0
months, and 18 patients (56%) had discontinued treatment. Of the 32 patients
enrolled, 28 were evaluable for response by independent radiologic review.
Objective response rate was 62% (95% CI, 45% to 77%), with one complete response
and 19 partial responses; duration of response was 21.0 months (95% CI, 17 to 25
months); and disease control rate was 81% (95% CI, 65% to 91%). The median
progression-free survival was 9.3 months (95% CI, 0 to 22 months) for all
patients and 19.3 months (95% CI, 1 to 37 months) for crizotinib-naive patients.
The median overall survival was 24 months (95% CI, 5 to 43 months). Of the eight
patients with brain metastases, intracranial disease control was reported in five
(63%; 95% CI, 31% to 86%). The most common adverse events (majority, grade 1 or
2) for all treated patients were diarrhea (78%), nausea (59%), and anorexia
(56%). Conclusion Ceritinib demonstrated potent clinical activity in patients
with ROS1-rearranged NSCLC who were heavily treated previously with multiple
lines of chemotherapy.
PMID- 28520532
TI - Effectiveness of SmartGuard Technology in the Prevention of Nocturnal
Hypoglycemia After Prolonged Physical Activity.
AB - BACKGROUND: The prevention of postexercise nocturnal hypoglycemia after prolonged
physical activity using sensor-augmented pump (SAP) therapy with predictive low
glucose management (PLGM) has not been well studied. We conducted a study at a
pediatric diabetes camp to determine whether a SAP with PLGM reduces the
frequency of nocturnal hypoglycemia after prolonged physical activity more
effectively than a SAP with a carbohydrate intake algorithm. METHODS: During a 1
week sport camp, 20 children (aged 10-13 years) with type 1 diabetes (T1D)
managed by SAP therapy either with (n = 7) or without PLGM (n = 13) were studied.
The hypoglycemia management strategy and the continuous glucose monitoring
(CGM)/PLGM settings were standardized. The incidence, severity, and duration of
hypoglycemia and carbohydrate intake were documented and compared. RESULTS: The
PLGM system was activated on 78% of all nights (once per night on average). No
difference was found between the SAP and PLGM groups in the mean overnight
glucose curve or mean morning glucose (7.8 +/- 2 mmol/L vs. 7.4 +/- 3 mmol/L).
There was no difference in the frequency and severity of hypoglycemia. However,
the SAP group consumed significantly more carbohydrates to prevent and treat
hypoglycemia than those in the PLGM group; the values were 10 +/- 2 and 1 +/- 2
gS (P < 0.0001) in the SAP and PLGM groups, respectively. Moreover, the SAP group
spent a significantly longer time in hypoglycemia (64 +/- 2 min vs. 38 +/- 2 min,
P < 0.05). We observed a difference in the time distribution of nocturnal
hypoglycemia (10 to 12 p.m. in the PLGM group and 3 to 7 a.m. in the SAP group, P
< 0.05). CONCLUSION: With PLGM system, euglycemia after prolonged physical
activity was largely maintained with a minimal carbohydrate intake.
PMID- 28520533
TI - A Fully Automated High-Throughput Zebrafish Behavioral Ototoxicity Assay.
AB - Zebrafish animal models lend themselves to behavioral assays that can facilitate
rapid screening of ototoxic, otoprotective, and otoregenerative drugs.
Structurally similar to human inner ear hair cells, the mechanosensory hair cells
on their lateral line allow the zebrafish to sense water flow and orient head-to
current in a behavior called rheotaxis. This rheotaxis behavior deteriorates in a
dose-dependent manner with increased exposure to the ototoxin cisplatin, thereby
establishing itself as an excellent biomarker for anatomic damage to lateral line
hair cells. Building on work by our group and others, we have built a new, fully
automated high-throughput behavioral assay system that uses automated image
analysis techniques to quantify rheotaxis behavior. This novel system consists of
a custom-designed swimming apparatus and imaging system consisting of network
controlled Raspberry Pi microcomputers capturing infrared video. Automated
analysis techniques detect individual zebrafish, compute their orientation, and
quantify the rheotaxis behavior of a zebrafish test population, producing a
powerful, high-throughput behavioral assay. Using our fully automated biological
assay to test a standardized ototoxic dose of cisplatin against varying doses of
compounds that protect or regenerate hair cells may facilitate rapid translation
of candidate drugs into preclinical mammalian models of hearing loss.
PMID- 28520534
TI - CpG Island Methylation Correlates with the Use of Alternative Promoters for USP44
Gene Expression in Human Pluripotent Stem Cells and Testes.
AB - Deubiquitinating enzymes may play a major regulatory role in pluripotent stem
cells (PSCs), but few studies have investigated this topic. Within this family of
enzymes, we found that the ubiquitin-specific peptidase USP44, is highly
expressed in embryonic stem cells, induced PSCs (iPSCs), and testes as compared
with differentiated progenies and somatic organs. Analysis by quantitative
polymerase chain reaction and 5' RACE showed that alternate promoters are
responsible for expression in PSCs and organs. We noticed seven regions of
transcription initiation, some of them with cell- or tissue-specific activity.
Close analysis showed that one of the promoters involved in stem cell- and testis
specific activity is differentially regulated in those tissues. At the epigenetic
level, USP44 transcription was correlated with DNA methylation of a CpG island
close to the main promoter region. These data imply a complex picture where
regulating factors such as OCT4 may interact with other epigenetic mechanisms to
regulate USP44 expression in PSCs and testes.
PMID- 28520535
TI - Optimal Z-Score Use in Surgical Decision-Making in Pulmonary Atresia With Intact
Ventricular Septum.
AB - OBJECTIVES: In the surgical treatment of pulmonary atresia with intact
ventricular septum, the size of the tricuspid valve annulus (as measured by z
scores) has emerged as a significant factor in deciding which repair to perform.
Various tricuspid valve annulus z-scores are reported as "cutoffs" for successful
biventricular repair. We aimed to determine whether the use of different z-score
data sets contributed to the gross variation in "cutoffs" for successful
biventricular repair reported in the literature. METHODS: A single search was
made of PubMed using the "advanced" setting with the following search terms:
pulmonary, atresia, intact, septum, z, and score. The filters "title" and
"title/abstract" were used for the first four and last two terms, respectively;
the instruction "AND" combined all terms. Articles that identified which z-score
data set was used in patients with biventricular repairs were included. RESULTS:
From 13 articles, 1,392 patients were studied, 410 (29.5%) of which achieved
biventricular repair. Three z-score data sets were quoted; mean tricuspid valve
annulus z-scores in biventricular repair patients ranged between -0.53 and -5.1.
After correcting for discrepancies between z-score data sets, no study reported a
mean tricuspid valve annulus z-score <-2.8 in biventricular repair patients and
83.3% reported mean tricuspid valve annuli z-scores >-1.7. CONCLUSION: The use of
varied tricuspid valve annuli z-score data sets may have contributed to gross
variations in reported "cutoffs" for successful biventricular repair. This could
lead to inappropriate surgical pathway allocation.
PMID- 28520536
TI - Anticoagulation for Interventional Extracardiac Fontan.
PMID- 28520537
TI - Anomalous Origin of Right Coronary Artery From Left Coronary Sinus-13 Cases
Treated With the Reimplantation Technique.
AB - OBJECTIVES: Anomalous aortic origin of a coronary artery is uncommon but
potentially clinically significant. Manifestations vary from asymptomatic
patients to those who present with angina pectoris, myocardial infarction, heart
failure, syncope, arrhythmias, and sudden death. We describe our experience with
surgical reimplantation and results at midterm follow-up. METHODS: Between
February 2003 and July 2016, a total of 13 patients with anomalous origin of the
right coronary artery (RCA) from the left sinus underwent surgical
reimplantation. RESULTS: Mean age was 39 years (range, 11-72 years). Eight
patients presented with dyspnea and angina, two with acute myocardial infarction,
and the remaining three were studied for atypical chest pain and ventricular
premature contractions. Definitive diagnosis was achieved with coronary
angiography in eight cases and with computed tomography scan in five. In all
cases, the anomalous origin of the RCA from the left sinus had an intramural
course except one case with interarterial (but not intramural) course. At
operation, the RCA was dissected at the takeoff from the intramural course and
reimplanted into the right sinus of Valsalva. There was no mortality. One patient
had associated atherosclerotic coronary artery disease that required stent
placement postoperatively. After a mean follow-up of 65 months (maximum 12
years), all patients are asymptomatic and have returned to exercise without
limitations. CONCLUSIONS: The reimplantation technique provides a good
physiological and anatomical repair, eliminates a slit-like ostium, avoids
compression of the coronary artery between the aorta and the pulmonary artery,
and gives similar results to the unroofing technique.
PMID- 28520539
TI - Left Ventricular Noncompaction With Muscular Ventricular Septal Defect in Mother
and Son.
PMID- 28520538
TI - Treatment Strategies for Paradoxical Hypertension Following Surgical Correction
of Coarctation of the Aorta in Children.
AB - BACKGROUND: Paradoxical hypertension after repair of coarctation of the aorta is
a well-known phenomenon. The pathogenesis involves the activation of the
sympathetic nervous system (first phase) and renin-angiotensin system (second
phase). Only a limited number of different treatment strategies have been
published in the literature, without any comparative studies. METHODS: Our aim
was to describe the current international practice variation surrounding
pharmacological treatment currently being employed to treat paradoxical
hypertension following the repair of coarctation of the aorta in children. We
performed an online survey among 197 members of the Pediatric Cardiac Intensive
Care Society. We also conducted a systematic review of the literature regarding
the treatment of paradoxical hypertension. RESULTS: Eighty-eight people (45%),
from 62 different centers, responded and answered the questions regarding blood
pressure control. Nitroprusside is the first drug of choice for initial blood
pressure control in 66% of respondents, esmolol in 11%, labetalol in 11%, and
angiotensin-converting enzyme inhibitors (ACEIs) are used by 3% of respondents.
For oral blood pressure control after discharge from the pediatric intensive care
unit, 75% of respondents use ACEIs, 18% use labetalol, and 12% use other beta
blockers (propranolol, carvedilol, atenolol, metoprolol). The systematic review
identified 14 articles reporting pharmacological treatment of direct
postoperative hypertension following coarctation repair. CONCLUSION: There is
wide practice variability, due to the lack of sufficient compelling evidence. The
majority (66%) of caregivers use nitroprusside to control blood pressure in the
acute postoperative phase. The ACEIs are the drug of choice for chronic blood
pressure control.
PMID- 28520540
TI - Virtual Surgery for Conduit Reconstruction of the Right Ventricular Outflow
Tract.
AB - PURPOSE: Virtual surgery involves the planning and simulation of surgical
reconstruction using three-dimensional (3D) modeling based upon individual
patient data, augmented by simulation of planned surgical alterations including
implantation of devices or grafts. Here we describe a case in which virtual
cardiac surgery aided us in determining the optimal conduit size to use for the
reconstruction of the right ventricular outflow tract. DESCRIPTION: The patient
is a young adolescent male with a history of tetralogy of Fallot with pulmonary
atresia, requiring right ventricle-to-pulmonary artery (RV-PA) conduit
replacement. Utilizing preoperative magnetic resonance imaging data, virtual
surgery was undertaken to construct his heart in 3D and to simulate the
implantation of three different sizes of RV-PA conduit (18, 20, and 22 mm).
EVALUATION: Virtual cardiac surgery allowed us to predict the ability to implant
a conduit of a size that would likely remain adequate in the face of continued
somatic growth and also allow for the possibility of transcatheter pulmonary
valve implantation at some time in the future. Subsequently, the patient
underwent uneventful conduit change surgery with implantation of a 22-mm Hancock
valved conduit. As predicted, the intrathoracic space was sufficient to
accommodate the relatively large conduit size without geometric distortion or
sternal compression. CONCLUSION: Virtual cardiac surgery gives surgeons the
ability to simulate the implantation of prostheses of different sizes in relation
to the dimensions of a specific patient's own heart and thoracic cavity in 3D
prior to surgery. This can be very helpful in predicting optimal conduit size,
determining appropriate timing of surgery, and patient education.
PMID- 28520541
TI - Outcomes and Prognostic Factors for Adult Patients With Congenital Heart Disease
Undergoing Primary or Reoperative Systemic Atrioventricular Valve Surgery.
AB - BACKGROUND: Adults with congenital heart disease (ACHD) undergoing systemic
atrioventricular valve (SAVV) surgery are a complex, understudied population. We
assessed midterm outcomes and prognostic factors in ACHD undergoing SAVV surgery.
METHODS: We performed retrospective evaluation of ACHD undergoing SAVV surgery
from January 2005 to February 2016: 14 (33%) patients with congenital mitral
valve stenosis/regurgitation, 15 (35%) with atrioventricular septal defect
(AVSD), and 14 (33%) with congenitally corrected transposition of the great
arteries (ccTGA) with systemic tricuspid valve regurgitation. Adverse events were
defined as mortality, reoperation on SAVV, and late more-than-moderate (>
moderate) SAVV regurgitation. Statistical analysis was performed using Fisher's
exact test and one-way analysis of variance as well as univariate and
multivariate risk factor analysis. RESULTS: Fifteen (35%) patients had
preoperative systemic ventricular dysfunction, including 13 patients with ccTGA
(93%, P < .001). Twenty-three (54%) patients underwent valve repair, 20 (47%)
patients underwent replacement, and 20 (47%) patients underwent an associated
procedure. Replacement was higher in patients with ccTGA (86%) than the other
groups ( P < 0.01). Thirty-seven patients (91% of survivors) were free of
significant SAVV regurgitation at last follow-up, with patients with AVSD having
greater regurgitation grades compared to the other groups ( P < 0.01). In
hospital mortality, late mortality, late > moderate SAVV regurgitation, and SAVV
reoperation rates were 5% (n = 2), 2% (n = 1), 9% (n = 3), and 7% (n = 3),
respectively. On multivariate analysis, predischarge SAVV regurgitation grade was
the only significant predictor of adverse events (odds ratio = 8.2, 95%
confidence interval: 1.1-63.8, P = .045). CONCLUSION: Overall outcomes in this
challenging population are good. The single factor associated with adverse events
was predischarge SAVV regurgitation grade.
PMID- 28520542
TI - Hybrid Palliation for Interrupted Aortic Arch With Small Aortic Valve.
AB - OBJECTIVES: Open heart surgery for interrupted aortic arch in the neonatal period
is still a high-risk procedure related in part to patient factors such as low
birth weight, other morphologic anomalies, and, especially, small aortic valve
size. Recently, we performed hybrid palliation with bilateral pulmonary artery
banding and ductal stenting as the first-stage palliation for such cases. In this
study, the outcomes of this procedure were examined. METHODS: Six cases of
interrupted aortic arch with a small aortic valve underwent the hybrid procedure
in the neonatal period in our institute from 2010 to 2015 (mean age: 6.8 days,
mean body weight: 3.2 kg, mean z score of the aortic valve annulus: -8.3). Their
postoperative clinical courses and results of the second-stage surgery were
evaluated. RESULTS: No mortality or severe morbidity was seen in association with
initial hybrid palliation. Five of six patients were discharged from the
hospital; the one exception had a significant urinary tract anomaly. None needed
an additional catheter intervention or surgical procedure postoperatively. All
surviving patients underwent second-stage surgery; three had biventricular repair
by the conventional method or Damus-Kaye-Stansel anastomosis with the Rastelli
procedure and the other three proceeded toward staged Fontan reconstruction.
Growth of the aortic valve was seen in four patients, and increased indexed left
ventricle volume was recognized in one after the palliation. CONCLUSION: Hybrid
palliation could be useful not only to avoid high-risk neonatal surgery but also
to allow for eventual selection of the second-stage surgery based on the
observations of potential interval development of left ventricular structures.
PMID- 28520543
TI - Double Aortic Arch With a Retroaortic Innominate Vein: A Rare Association
Diagnosed Using Cardiac Magnetic Resonance Imaging.
PMID- 28520544
TI - Repair of Complete Atrioventricular Septal Defects With Decellularized
Extracellular Matrix: Initial and Midterm Outcomes.
AB - OBJECTIVE: Since April 2010, our institution has repaired complete
atrioventricular septal defects (CAVSDs) with a two-patch technique utilizing
CorMatrix extracellular material. This material is potentially an attractive
patch because of its theorized eventual integration with the host tissue. We
sought to analyze initial outcomes of CAVSD repair with CorMatrix. METHODS: Data
were collected on consecutive pediatric (age <18) patients receiving two-patch
CAVSD repairs with CorMatrix at a single institution from April 2010 to July
2014. Baseline and perioperative characteristics were evaluated. Echocardiograms
were evaluated in both the immediate postoperative period and the most recent
postoperative follow-up. Variables analyzed included left AV valve performance,
residual shunting, left ventricular outflow tract (LVOT) gradient, morbidity, and
mortality. RESULTS: Fifteen patients were identified. The average age at
operation was 205 days, with mean follow-up time at 1,364 days. Echocardiograms
revealed the following: 12 (80%) patients showed either improved or stable left
AV valve performance remaining at "mild" or less insufficiency, while two (13%)
declined from "none" to mild and one (7%) from mild to "severe," which required
reoperation. There was no residual shunting or LVOT obstruction at follow-up. The
single (7%) reoperation was performed after three years due to left AV valve zone
of apposition dehiscence. No permanent pacemakers were needed, and no deaths were
reported. CONCLUSION: Our initial experience with CorMatrix in the repair of
CAVSD in children has resulted in good initial and midterm outcomes. The
CorMatrix patch remained stable through midterm follow-up, thus may be
efficacious for use in CAVSD repair.
PMID- 28520546
TI - A Simplified Technique for Interventional Extracardiac Fontan.
PMID- 28520545
TI - Hemodynamic Profile of Acute Kidney Injury Following the Fontan Procedure: Impact
of Renal Perfusion Pressure.
AB - BACKGROUND: Acute kidney injury (AKI) is common following cardiopulmonary bypass.
Fontan completion may result in systemic venous hypertension and low cardiac
output, reducing renal perfusion pressure (RPP) and further increasing the risk
of AKI. We investigated the incidence and risk factors for post-Fontan AKI.
METHODS: Single-center retrospective study of children undergoing Fontan
completion from 2005 to 2012. Demographic and hemodynamic variables were assessed
for association with AKI. Subgroup analysis was performed on patients with high
grade AKI (creatinine increase of >=2.0 * baseline). Vital sign data were
collected hourly for the first postoperative day. RESULTS: A total of 186
patients underwent Fontan at 3.1 (2.5-3.8) years of age and 13.5 kg (12.2-15.1).
Acute kidney injury occurred in 97 (52%) patients, with high-grade AKI in 52
(28%). Univariate analysis identified reduced RPP in patients with AKI compared
to those without AKI, 50 (45-56) mm Hg versus 58 (54-61) mm Hg ( P < .0001), due
to lower mean arterial blood pressure, 63 (60-69) versus 70 (66-73) mm Hg ( P <
.0001), and higher central venous pressure, 14 (12-16) versus 13 (11-14) mm Hg, (
p < .0001). Multivariable logistic regression and classification tree analyses
further identified elements of RPP as significant predictors of AKI, especially
high-grade AKI. Postoperative intubation was linked to AKI development. Patients
with AKI had decreased postoperative urine output with increased colloid
requirements, duration of chest tube insertion, and hospital length of stay.
CONCLUSION: Acute kidney injury occurs frequently following the Fontan procedure.
Associated factors include reduced RPP, high colloid requirements, and
postoperative intubation. Targeted hemodynamic interventions may serve to reduce
the incidence of post-Fontan AKI.
PMID- 28520547
TI - Cardiovascular Magnetic Resonance of the Ross II Procedure: Long-Term
Postoperative Imaging.
PMID- 28520548
TI - Intracoronary Hypothermia Before Reperfusion to Reduce Reperfusion Injury in
Acute Myocardial Infarction: A Novel Hypothesis and Technique.
AB - Because current reperfusion strategies in acute myocardial infarction (AMI) seem
to be exhausted in terms of additional mortality benefit, there remains a need
for new methods to attenuate reperfusion injury and, thereby, further reduce
myocardial infarct size and improve long-term survival. Therapeutic hypothermia
(32-35 degrees C) diminishes reperfusion injury and reduces infarct size in a
variety of animal models of AMI if provided before reperfusion. In human studies
this reduction has not been confirmed so far, most likely because systemic
cooling acts slowly, and therefore, the target temperature is not reached in time
or at all in a substantial number of patients. Furthermore, systemic cooling can
cause adverse effects such as severe shivering, volume overload, and an enhanced
adrenergic state. In most randomized clinical trials, however, subgroups of
patients with anterior myocardial infarction that reached the target temperature
before reperfusion did show a reduction in infarct size. To transform therapeutic
hypothermia into a clinically feasible treatment for AMI, its method must be
modified. An ideal technique should be quick enough to achieve sufficient
myocardial hypothermia before reperfusion, without significant delay and without
the adverse effects of systemic cooling. In this review, we propose a novel,
potentially feasible method of selective intracoronary hypothermia to overcome
the problems encountered with prior techniques.
PMID- 28520551
TI - Strategies for Sustained Weight Management: Perspectives From African American
Patients With Type 2 Diabetes.
AB - Purpose The purpose of this study was to identify effective strategies for
sustained weight management used by African American patients with obesity and
type 2 diabetes. Methods In this study, nominal group technique was used to
identify effective strategies for weight management used by 12 African Americans
with overweight/obesity and type 2 diabetes who successfully lost or maintained
their weight after completing DECIDE (Decision-making Education for Choices In
Diabetes Everyday), a 9-module, literacy-adapted diabetes and cardiovascular
disease (CVD) education and problem-solving training program. Results
Participants generated a list of 101 strategies that covered 4 domains:
nutrition, physical activity, cognitive-behavioral strategies, and other. Self
monitoring and relying on social support were the top 2 strategies for weight
maintenance. Conclusion Future obesity studies should consider including
friends/family as well as electronic tools to facilitate self-monitoring and
regular practice of behavioral strategies for long-term success.
PMID- 28520550
TI - Outcomes That Matter to Teens With Type 1 Diabetes.
AB - Purpose The purpose of the study was to describe outcomes that matter to teens
with type 1 diabetes. Understanding outcomes that matter to teens could support
successful interventions to improve diabetes self-management. Methods Fifty
publicly available posts published in the "teen" sections of 2 major diabetes
online forums between 2011 and 2013 were analyzed using qualitative research
methods. From each post, content and descriptive data (eg, duration of diabetes
and age) were collected. Two members of the research team independently used open
coding techniques to identify outcomes (defined as impacts or consequences of
type 1 diabetes) and organized them into themes and subthemes. A codebook was
jointly developed to facilitate the identification of meaningful outcomes from
the posts. Results Teens' average age was 15.7 years, and the average time since
diabetes diagnosis was 6.3 years. The 3 most commonly mentioned outcomes were (1)
interactions with peers ("I want to talk to someone who understands"), (2)
emotional well-being ("Diabetes makes me want to cry"), and (3) blood glucose
management ("My blood sugar never goes down"). Other identified outcomes included
(4) physical well-being, (5) education and motivation of others, (6) family
interactions, (7) academic achievement, and (8) interactions with important
others such as teachers. Conclusions While teens are concerned about control of
their blood glucose, there are many other outcomes that matter to them. Health
care providers and diabetes educators may want to consider these other outcomes
when motivating teens with type 1 diabetes to improve blood glucose control.
PMID- 28520552
TI - Prestimulus Inhibition of Saccades in Adults With and Without Attention
Deficit/Hyperactivity Disorder as an Index of Temporal Expectations.
AB - Knowing when to expect important events to occur is critical for preparing
context-appropriate behavior. However, anticipation is inherently complicated to
assess because conventional measurements of behavior, such as accuracy and
reaction time, are available only after the predicted event has occurred.
Anticipatory processes, which occur prior to target onset, are typically measured
only retrospectively by these methods. In this study, we utilized a novel
approach for assessing temporal expectations through the dynamics of prestimulus
saccades. Results showed that saccades of neurotypical participants were
inhibited prior to the onset of stimuli that appeared at predictable compared
with less predictable times. No such inhibition was found in most participants
with attention-deficit/hyperactivity disorder (ADHD), and particularly not in
those who experienced difficulties in sustaining attention over time. These
findings suggest that individuals with ADHD, especially those with sustained
attention deficits, have diminished ability to benefit from temporal
predictability, and this could account for some of their context-inappropriate
behaviors.
PMID- 28520553
TI - CDC's Public Health Surveillance of Cancer.
AB - Routine data collection efforts are a necessary, often underappreciated,
component of nearly all cancer research and prevention efforts. Public health
cancer surveillance data are crucial for identifying needs, planning
interventions, directing public health resources, and evaluating the overall
effectiveness of initiatives aimed at preventing or treating cancer and its
negative health consequences. As the nation's health protection agency, the
Centers for Disease Control and Prevention (CDC) provides resources for disease
surveillance systems to help protect our nation against expensive and dangerous
health threats, including cancer. Therefore, public health surveillance is a core
function of CDC. In this article we briefly describe CDC's approach to cancer
surveillance in our public health programs and other federal initiatives to
monitor cancer-related outcomes. We also describe our premier cancer incidence
surveillance system, the National Program of Cancer Registries, and discuss uses
and applications of the program's critical cancer data.
PMID- 28520555
TI - Relaxation lifetimes of plasmonically enhanced hybrid gold-carbon nanotubes
systems.
AB - Recently, we introduced a novel hybridization route for carbon nanotubes using
gold nanoparticles, whose close proximity neatly enhances their radiative
emission. Here we investigate the mechanisms behind the enhancement by monitoring
the de-excitation dynamics of our pi-hybrids through two-color pump-probe time
resolved spectroscopy. The de-excitation process reveals a fast component and a
slow component. We find that the presence of gold prominently affects the fast
processes, indicating a stronger influence of the gold nanoparticle on the intra
band non-radiative relaxation than on the inter-band recombination of the single
walled carbon nanotube. By evaluating the de-excitation times, we estimate the
balance between near-field pumping and the faster metal-induced de-excitation
contributions, proving the enhanced pumping to be the leading mechanism.
PMID- 28520557
TI - First-principles investigation of intrinsic defects and self-diffusion in ordered
phases of V2C.
AB - The self-diffusion behavior of vanadium subcarbide (V2C) is investigated using
density functional theory calculations, owing to its potential application as a
diffusion barrier in nuclear applications. Three ordered V2C structures, two of
which correspond to experimentally observed phases, are characterized in terms of
their equilibrium structural, electronic and elastic properties. Our model for
self-diffusion in V2C considers diffusion of carbon and vanadium to occur
separately on each sublattice. Two sets of self-diffusion coefficients are
calculated for each structure: one for vacancy-mediated diffusion of vanadium and
the other for interstitial diffusion of carbon. Calculated activation energies
and diffusion prefactors are compared to experimental data for the cubic
transition metal carbides as there is no experimental self-diffusion data for any
of the hexagonal subcarbides.
PMID- 28520554
TI - The Multiple Signals That Control Tuber Formation.
PMID- 28520556
TI - Breast tissue stiffness estimation for surgical guidance using gravity-induced
excitation.
AB - Tissue stiffness interrogation is fundamental in breast cancer diagnosis and
treatment. Furthermore, biomechanical models for predicting breast deformations
have been created for several breast cancer applications. Within these
applications, constitutive mechanical properties must be defined and the accuracy
of this estimation directly impacts the overall performance of the model. In this
study, we present an image-derived computational framework to obtain
quantitative, patient specific stiffness properties for application in image
guided breast cancer surgery and interventions. The method uses two MR
acquisitions of the breast in different supine gravity-loaded configurations to
fit mechanical properties to a biomechanical breast model. A reproducibility
assessment of the method was performed in a test-retest study using healthy
volunteers and was further characterized in simulation. In five human data sets,
the within subject coefficient of variation ranged from 10.7% to 27% and the
intraclass correlation coefficient ranged from 0.91-0.944 for assessment of
fibroglandular and adipose tissue stiffness. In simulation, fibroglandular
content and deformation magnitude were shown to have significant effects on the
shape and convexity of the objective function defined by image similarity. These
observations provide an important step forward in characterizing the use of
nonrigid image registration methodologies in conjunction with biomechanical
models to estimate tissue stiffness. In addition, the results suggest that
stiffness estimation methods using gravity-induced excitation can reliably and
feasibly be implemented in breast cancer surgery/intervention workflows.
PMID- 28520558
TI - Data-driven event-by-event respiratory motion correction using TOF PET list-mode
centroid of distribution.
AB - Data-driven respiratory gating techniques were developed to correct for
respiratory motion in PET studies, without the help of external motion tracking
systems. Due to the greatly increased image noise in gated reconstructions, it is
desirable to develop a data-driven event-by-event respiratory motion correction
method. In this study, using the Centroid-of-distribution (COD) algorithm, we
established a data-driven event-by-event respiratory motion correction technique
using TOF PET list-mode data, and investigated its performance by comparing with
an external system-based correction method. Ten human scans with the pancreatic
beta-cell tracer 18F-FP-(+)-DTBZ were employed. Data-driven respiratory motions
in superior-inferior (SI) and anterior-posterior (AP) directions were first
determined by computing the centroid of all radioactive events during each short
time frame with further processing. The Anzai belt system was employed to record
respiratory motion in all studies. COD traces in both SI and AP directions were
first compared with Anzai traces by computing the Pearson correlation
coefficients. Then, respiratory gated reconstructions based on either COD or
Anzai traces were performed to evaluate their relative performance in capturing
respiratory motion. Finally, based on correlations of displacements of organ
locations in all directions and COD information, continuous 3D internal organ
motion in SI and AP directions was calculated based on COD traces to guide event
by-event respiratory motion correction in the MOLAR reconstruction framework.
Continuous respiratory correction results based on COD were compared with that
based on Anzai, and without motion correction. Data-driven COD traces showed a
good correlation with Anzai in both SI and AP directions for the majority of
studies, with correlation coefficients ranging from 63% to 89%. Based on the
determined respiratory displacements of pancreas between end-expiration and end
inspiration from gated reconstructions, there was no significant difference
between COD-based and Anzai-based methods. Finally, data-driven COD-based event
by-event respiratory motion correction yielded comparable results to that based
on Anzai respiratory traces, in terms of contrast recovery and reduced motion
induced blur. Data-driven event-by-event respiratory motion correction using COD
showed significant image quality improvement compared with reconstructions with
no motion correction, and gave comparable results to the Anzai-based method.
PMID- 28520559
TI - A comparative study of efficacy of single rooted and double rooted teeth in age
estimation using dentin translucency.
AB - BACKGROUND: Among various methods of age estimation using dental tissues,
measurement of root dentin translucency (RDT) is said to be the most accurate.
Numerous studies have estimated age by measuring RDT in single and double rooted
teeth and have shown conflicting results. Only few studies have compared efficacy
of using single and double rooted teeth for RDT measurement in age estimation.
AIM: To analyze the efficacy of single rooted teeth (SRT) and double rooted teeth
(DRT) for measurement of sclerotic dentin (SD) and age estimation. METHOD: Study
was conducted on 120 freshly extracted SR and DR teeth with 60 teeth in each
group. Ground sections of 150 u thickness were observed under stereomicroscope
and photographed. The sclerotic dentin length was measured on the images captured
using image analysis software. RESULTS AND CONCLUSION: The present study did not
reveal significant difference (p = 0.012) between SRT and DRT when RDT was used
for age estimation. However DRT provided more accurate age estimation than SRT
with less mean age difference.
PMID- 28520560
TI - Assessing age-related change in Japanese mental foramen opening direction using
multidetector computed tomography.
AB - OBJECTIVE: The purpose of this study was to investigate how the opening direction
of the mental foramen (MF) changes with age in a Japanese population using multi
detector computed tomography (MDCT). METHODS: Post-mortem MDCT scans of 121
Japanese subjects (66 males and 55 females) were carried out where all subjects
possessed at least twenty teeth, including molar teeth, in the upper and lower
jaws. Two angles of the mental foramen opening were measured, namely the superior
inferior angle in the coronal plane and anterior-posterior angle in the
transverse plane, on the CT reconstructed images. The associations between age
and these two angles were evaluated using a multiple regression analysis.
RESULTS: For male subjects, the relationship between the superior-inferior angle
and age was a quadratic curve (p < 0.001). This angle increased until the subject
reached their early 50s and then the angle decreased with age. In the transverse
plane, there was a linear relation between the anterior-posterior angle and age
(p=0.002).It was noted also that the angle decreased with age. By contrast,
however, no significant associations between the two angles and age for either
measurement were noted for female subjects. This study demonstrated that the
opening direction of the mental foramen changes with age in Japanese male
subjects. By contrast this change in the opening direction of the mental foramen
was not demonstrated in Japanese female subjects. In male subjects, the opening
direction moves superiorly until the individual reaches their early 50s, and then
moves inferiorly with advancing age. It also shifts from a posterior to an
anterior position with age. CONCLUSION: These observed change differ from the
results of previous studies. The findings could be useful for forensic science as
they demonstrate a change in the position of mental foramen in a sample of
contemporaneous male Japanese subjects.
PMID- 28520561
TI - A comparative evaluation of the applicability of two adapted Haavikko methods for
age estimation of 5-15 year old Indian children.
AB - Dental age determination methods that require the assessment of all teeth are
tedious and time-consuming. Adapted methods that assess fewer teeth may be more
easily applicable. The present study compared the applicability of two adapted
Haavikko methods which evaluate seven mandibular teeth (HAM1) and four reference
teeth (HAM2) in a population of 5 to 15 year-old Indian children. The HAM1 method
underestimated age by -0.17 +/- 0.80 years, -0.29 +/- 0.83 years and -0.22 +/-
0.82 years in boys, girls and the total sample respectively, while the HAM2
method underestimated age by -0.34 +/- 0.88 years, -0.51 +/- 0.82 years and -0.41
+/- 0.86 years in boys, girls and the total sample, respectively. Significant
gender-based differences were observed in mean DA-CA with both methods (p <
0.05). While both methods could be used for age estimation of the present
population, the HAM1 method was the more accurate of the two.
PMID- 28520563
TI - Multiple deaths caused by a fire in a factory: identification and investigative
issues.
AB - The article presents a case of multiple casualties following a textile factory
fire. The incident required a full DVI team similar to large mass-disaster
because of the specific operational aspects and identification difficulties. The
autopsy results were consistent with death by fire and the toxicological
investigations revealed carbon monoxide poisoning in four cases (HbCO% ranging
between 88,05 and 95,77), two deaths by cyanide intoxication (with concentrations
between 5,17 and 8,85 mcg/ml), and in one case there was a synergistic effect of
the two substances (carbon monoxide and cyanide). The identification, carried out
in accordance with INTERPOL protocols, encountered serious difficulties in the AM
phase primarily due to a language barrier and the lack of any dental or medical
information relating to the victims. Secondary identifiers proved to be very
useful in corroborating possible identities. As a result of the combined efforts
of a team of experts the identity of each victim was determined and in all cases
at least one primary identifier was used in the identification process. The
deployment of DVI teams composed of forensic experts from different fields of
expertise and well acquainted with DVI procedures, is essential in events
involving multiple casualties that may also include foreign victims. The DVI team
should intervene not only in PM examinations but also in the collection of AM
data for those individuals not accounted for and by helping police in contacting
families of missing people.
PMID- 28520562
TI - Reliability and repeatability of pulp volume reconstruction through three
different volume calculations.
AB - OBJECTIVE: To test the variability of the volume measurements when different
segmentation methods are applied in pulp volume reconstruction. MATERIALS AND
METHODS: Osirix(r) and ITK-SNAP software were used. Different segmentation
methods (Part A) and volume approaches (Part B) were tested in a sample of 21
dental CBCT's from upper canines. Different combinations of the data set were
also tested on one lower molar and one upper canine (Part C) to determine the
variability of the results when automatic segmentation is performed. RESULTS:
Although the obtained results show correlation among them(r > 0.75), there is no
evidence that these methods are sensitive enough to detect small volume changes
in structures such as the dental pulp canal (Part A and Part B). Automatic
segmentation is highly susceptible to be affected by small variations in the
setting parameters (Part C). CONCLUSIONS: Although the volumetric reconstruction
and pulp/tooth volume ratio has not shown better results than methods based on
dental radiographs, it is worth to persevere with the research in this area with
new development in imaging techniques.
PMID- 28520564
TI - Normothermic Cardiopulmonary Bypass in Patient With Waldenstrom's
Macroglobulinemia and Cryoglobulinemia: A Case Report.
AB - Waldenstrom's macroglobulinemia (WM) manifests as hyperviscosity syndrome.
Cryoglobulinemia, which may increase blood viscosity or induce thrombosis in
association with decreased body temperature, can occur in combination with WM. We
describe the management of an 82-year-old woman with WM, hyperviscosity syndrome,
and cryoglobulinemia who required open aortic valve replacement. Decreased body
temperature in this patient was prevented during cardiopulmonary bypass by using
a forced air warming system and normothermic cardioplegia with continuous warm
blood cardioplegia perfusion.
PMID- 28520565
TI - Use of a Tilting Orthopedic Fracture Table to Facilitate Proper Patient
Positioning During Intrathecal Neurolysis With Hyperbaric Phenol: A Case Report.
AB - We describe the case of a 41-year-old woman with metastatic cervical cancer and a
large mass eroding into the pelvis and left lumbosacral plexus. The patient had
intractable left lower extremity pain refractory to standard therapies, and she
elected to undergo intrathecal neurolysis. A diagnostic intrathecal block was
performed at the T11-12 interspace followed by intrathecal neurolysis with 6%
phenol in glycerin on a subsequent date. During both procedures, we used a
tilting radiolucent orthopedic fracture table to maintain strict left lateral
supine positioning. A tilting orthopedic fracture table may be a valuable adjunct
to ensure positional stability during intrathecal neurolysis.
PMID- 28520566
TI - Essential Thrombocytosis and Labor Epidural Placement While on Aspirin: Assessing
Hemorrhagic Risks: A Case Report.
AB - Essential thrombocytosis (ET) is a rare disease with known thrombotic and
bleeding complications. We encountered a patient with a diagnosis of longstanding
Janus kinase-2 gene-negative ET on aspirin therapy presenting for labor epidural.
Evaluation of platelet function with point-of-care analysis using Plateletworks
in a community hospital setting allowed confirmation of adequate numbers of
functional platelets to support safe epidural placement. The relevant issues of
ET for anesthesia management with labor epidurals are discussed. Unique,
relevant, and unexpected findings from the platelet function testing are
presented.
PMID- 28520567
TI - Persistent Hypotension and Cerebral Swelling Resulting From Mesenteric Traction
Syndrome After Omental-to-Pial Pedicle Flap Transfer in a Young Woman With
Refractory Moyamoya Disease: A Case Report.
AB - Superficial temporal arterial to middle cerebral arterial anastomosis is often
the initial surgical treatment of Moyamoya disease. In refractory cases, placing
a pedicle flap of omentum over the ischemic brain has resulted in clinical
improvement or stabilization of symptoms. We present a case of persistent
mesenteric traction syndrome manifested by hypotension unresponsive to
conventional doses of vasopressors during and after pulling the omentum to the
brain. As prostacyclin is a major mediator of hypotension from mesenteric
traction syndrome and also a cerebral vasodilator, we discuss the possibility
that brain swelling may be a manifestation of mesenteric traction syndrome.
PMID- 28520568
TI - Endothelin A receptor antagonists in diabetic kidney disease.
AB - PURPOSE OF REVIEW: Despite optimal therapy of diabetic nephropathy with agents
blocking the renin-angiotensin-aldosterone system, the residual risk of
nephropathy progression to end-stage renal disease (ESRD) remains high. The
purpose of this review is to discuss the potential role of endothelin antagonism
as a therapeutic tool to reduce residual proteinuria and delay kidney injury
progression among patients with diabetic nephropathy. RECENT FINDINGS:
Preclinical studies have shown that endothelin receptor antagonists (ERAs) exert
proteinuria lowering and nephroprotective actions in experimental models of
diabetic nephropathy. ERAs reduce proteinuria in phase 2 trials that included
therapy with renin-angiotensin-aldosterone system blockers. Safety of these
agents and protection from ESRD needs to be demonstrated in phase 3 trials.
Excess risk of fluid retention and heart failure risk remains. SUMMARY: The
hypothesis that the antiproteinuric effect of endothelin antagonism may be
translated into a slower progression of diabetic nephropathy to ESRD is
investigated in ongoing randomized trials assessing 'hard' renal endpoints. ERAs
may represent a promising tool toward renoprotection in diabetic nephropathy by
individualizing therapy and mitigating the risk of heart failure, if these trials
are positive.
PMID- 28520569
TI - The meaningness of colon cancer sidedness.
PMID- 28520570
TI - Long-term exposure to MST-312 leads to telomerase reverse transcriptase
overexpression in MCF-7 breast cancer cells.
AB - Telomerase is an enzyme responsible for telomere maintenance in almost all human
cancer cells, but generally not expressed in somatic ones. Therefore,
antitelomerase therapy is a potentially revolutionary therapeutic strategy, and
the antitumor activity of telomerase inhibitors (TI) has been studied extensively
recently, mainly for breast cancer. However, the effects expected from treatment
with TI will appear only after many cell divisions, but the effects of this long
term approach are unknown. In this work, the consequences of 3120 h exposure of
human breast cancer cells to TI MST-312 were investigated. MCF-7 cells were
treated with MST-312 at a subtoxic concentration for a long time, and then cell
morphology, viability, senescence, and proliferation were analyzed by phase
contrast microscopy, MTT assay, beta-galactosidase test, and the trypan blue
exclusion assay, respectively. Also, chromosomal stability was evaluated by
classical cytogenetic analysis. The average length of telomeres and telomerase
reverse transcriptase expression were accessed by real-time PCR and real-time RT
PCR, respectively. The MST-312 showed cytotoxic action and promoted telomere
erosion, senescence, and chromosome aberrations, as expected, but in a small
proportion. Nevertheless, the proliferation rate of the culture was not affected.
As the main effect, the chronic exposure led to cell adaptation by overexpression
of telomerase in response to the inhibitor, which is a potential cause of
therapeutic failure and may be associated with a poor prognosis. In conclusion,
despite the high therapeutic potential of TIs such as MST-312, the molecular
outcomes of long-term exposure of tumors on these drugs have to be evaluated when
considering their clinical application, especially for breast cancer treatment.
PMID- 28520571
TI - Is Omentectomy Mandatory Among Early Stage (I, II) Malignant Ovarian Germ Cell
Tumor Patients? A Retrospective Study of 223 Cases.
AB - OBJECTIVE: The aim of the study was to investigate whether omentectomy (OMT) is
necessary in the operation for apparently early stage malignant ovarian germ cell
tumors (MOGCTs). METHODS AND MATERIALS: Searching medical records database of Sun
Yat-sen University Cancer Center from January 1, 1966, to November 30, 2015,
patients with MOGCTs were identified and their age, year of diagnosis, tumor
grade, histologic subtype, International Federation of Gynecology and Obstetrics
stage, nodal findings, gross observation of omentum, and performance of OMT were
assessed. Overall survivals of patients with or without OMT were compared using
Kaplan-Meier survival curves. RESULTS: A total of 223 MOGCT cases with clinically
early stage (stage I and II) disease and with the 3 common histological subtypes
of MOGCT were obtained, which include yolk sac tumor (YST), dysgerminoma (DSG),
and immature teratoma (IMT). There were 192 stage I cases and 31 stage II cases.
Fifty-four patients were diagnosed with YST, 61 with DSG, and 108 with IMT.
Omentectomy was performed as part of the initial surgery in 74.0% patients
(165/223) and was omitted in 26.0% patients (58/223). Chemotherapy was
administered in 88.3% (197/223) of all patients. The median follow-up was 82.0
months. The 10-year overall survival rates of the patients with and without OMT
were 90.5% and 98.1%, respectively (P = 0.156). Regarding different stages or
histological subtypes, the 10-year survival rates of the 2 groups were 92.0%
versus 97.9% (P = 0.324, stage I), 83.2% versus 100% (P = 0.351, stage II), 89.2%
versus 100% (P = 0.303, YST), 94.1% versus 100% (P = 0.470, DSG), and 89.4%
versus 96.0% (P = 0.405, IMT), respectively. CONCLUSIONS: In conclusion, OMT in
patients with clinically early stage MOGCT may not improve patient survival and
may be omitted.
PMID- 28520572
TI - Maxillary Sinus Augmentation for Dental Implant Rehabilitation of the Edentulous
Ridge: A Comprehensive Overview of Systematic Reviews.
AB - OBJECTIVES: The objective of this systemic review was to perform a comprehensive
overview of systematic reviews and meta-analyses of the maxillary sinus
augmentation procedure for implant rehabilitation in humans. The following were
evaluated in this overview: (1) anatomic variables affecting sinus augmentation,
(2) histomorphometric analysis of the grafted sinus, (3) volumetric changes after
sinus grafting, and (4) implant survival beyond 1 year. MATERIAL AND METHODS:
Electronic databases were searched for systematic reviews and meta-analyses of
implant-related sinus augmentation published from 1976 to September 2015. The
studies selected must identify itself as a systemic review or meta-analysis in
the title or abstract and must pertain to sinus augmentation. RESULTS: Thirty
three publications fulfilled the review criteria. The AMSTAR ratings for the 33
chosen reviews scored greater than 3 of 11, with 8 reviews scoring greater or
equal to 8 of 11. CONCLUSION: The outcome of this overview suggested that the
following will increase the success of sinus augmentation and survival of
implants placed in the grafted sinus: (1) the use of barrier membranes over the
lateral window when using a lateral approach to graft the sinus, (2) the use of
particulate autogenous bone with or without other substitute graft materials, (3)
sinus augmentation without the use of grafting materials may be considered
provided that the space between the sinus membrane and floor can be maintained,
(4) the use of rough-surfaced implants, (5) simultaneous implant placement with
residual bone height greater than 4 mm, and (6) the cessation of smoking.
PMID- 28520573
TI - Efficacy of non-invasive brain stimulation for people experiencing chronic pain.
PMID- 28520574
TI - Orthotopic liver transplantation changes the course of gastric antral vascular
ectasia: a case series from a transplant center.
AB - BACKGROUND AND AIM: Gastric antral vascular ectasia (GAVE) is an important cause
of upper gastrointestinal bleeding and anemia in patients with cirrhosis. The aim
of our study was to evaluate the effect of orthotopic liver transplantation (OLT)
on GAVE and associated anemia. PATIENTS AND METHODS: We performed a chart review
and identified all cirrhotic patients with GAVE who underwent OLT at the
University Of Alabama at Birmingham between 2005 and 2013. Population's
demographics, etiology of cirrhosis, comorbidities, presentation and treatment
modalities of GAVE, endoscopic and histopathologic reports, hemoglobin values
before and after transplant, and immunosuppressive regimens were collected.
RESULTS: Twelve patients were identified, mean age 52.4+/-4.4 years; seven were
men (58.3%); 11 (91.7%) were White; and 6 of 12 patients had biopsy-proven GAVE.
The most common etiology of cirrhosis in the cohort was chronic hepatitis C and
obesity was the most common chronic condition in 50 and 83.3%, respectively.
Anemia resolution was observed in 9/12 (75%) patients who underwent OLT with an
increase in hemoglobin from 8.1+/-2.4 (5.7-13.1) before transplant to 12.0+/-1.4
(10-15) after transplant (P<0.0001). Esophagogastroduodenoscopy after transplant
was performed in all 12 (100%) patients. The mean time between transplant and
post-OLT esophagogastroduodenoscopy was 13.8+/-18.28 (2-57) months; complete
resolution of GAVE was observed in 10 (83.3%) patients, with resolving GAVE in
one (8.3%) patient. CONCLUSION: GAVE is an important cause of anemia and upper
gastrointestinal bleeding in patients with liver cirrhosis. Our findings show
that liver transplantation can resolve GAVE and related anemia.
PMID- 28520576
TI - Editor's Note: ANESTHESIOLOGY 2017: Expanding the Richness and Reach.
PMID- 28520575
TI - Predictors of bile tree pathology in patients presenting with gallbladder
disease.
AB - BACKGROUND: Patients with gallstone disease can present with elevated liver
function tests (LFTs). It is often challenging to differentiate those with a
common bile duct (CBD) stone from those without a CBD stone on the basis of the
LFTs levels. In this study, we aim to evaluate the predictors of a CBD stones
among patients presenting with symptomatic gallbladder disease and elevated LFTs.
PATIENTS AND METHODS: We retrospectively examined all patients who had undergone
a cholecystectomy between January 2010 and December 2015. Patients with
symptomatic cholelithiasis and increased LFTs were included. Patient
characteristics, imaging findings, lab findings, endoscopic interventions, and
operative report were recorded and evaluated. The diagnosis of CBD stones was
made on the basis of ERCP and IOC findings. RESULTS: We included 354 patients in
the final analysis. Of these, 113 (32%) had confirmed choledocholithiasis. The
prevalence of CBD stones among biliary colic, acute cholecystitis, and
pancreatitis patients was 47, 25, and 26%, respectively. gamma-Glutamyl
transferase and direct bilirubin had the highest sensitivities for CBD stones
among these patients (83 vs. 79%). In the setting of biliary colic, total
bilirubin was highly predictive of CBD stones with a positive predictive value of
85%. In the setting of acute cholecystitis, elevated LFTs were even less
significant in predicting stones, with a positive predictive value of less than
40% for most. CONCLUSION: Although gamma-glutamyl transferase and bilirubin
levels showed a relatively higher sensitivity for CBDS compared with the other
LFTs, these were not reliable enough because of high false-positive as well as
false-negative values, especially in patients presenting with acute
cholecystitis.
PMID- 28520577
TI - The Effects of Remifentanil on Hemodynamic Response Attenuation After
Electroconvulsive Therapy Under Sevoflurane Anesthesia.
AB - PURPOSE: We evaluated the effects of a single loading dose of remifentanil (1
MUg/kg) administered as an adjunct to sevoflurane, on the duration of seizure
activity, recovery times, and hemodynamic profiles, during electroconvulsive
therapy. METHODS: The patients were randomly allocated to receive sevoflurane
saline (Group SS) or sevoflurane-remifentanil (Group SR). Sevoflurane (8%) was
initiated for anesthesia induction in both groups until loss of consciousness was
achieved. Remifentanil was then administered to Group SR via a 1-MUg/kg
intravenous bolus. Patients in Group SS received saline in the same manner. Mean
arterial pressure (MAP) and heart rate (HR) were recorded before anesthetic
induction (T1), at the loss of consciousness (T2), and at 0, 1, 3, and 10 minutes
after the electrical stimuli were completed (T3, T4, T5, and T6, respectively).
RESULTS: Compared with the baseline values, HR increased significantly in Group
SS at times T2 and T4 to T6 and decreased significantly in Group SR at time T2.
When the groups were compared, we found that HR decreased significantly in Group
SR at T2 and T4 to T6. Compared with baseline, MAP increased in Group SS between
T3 and T6, and MAP decreased in Group SR at T2 and increased at T3 to T4. Mean
arterial pressure decreased to a greater extent in Group SR than in Group SS
during the T2 to T6 period. There were no group differences in seizure duration
or recovery time. CONCLUSIONS: The addition of 1-MUg/kg remifentanil to
anesthetic induction with sevoflurane attenuated the acute hemodynamic response
to electroconvulsive therapy under sevoflurane anesthesia without adversely
affecting the duration of seizure activity or the recovery profile.
PMID- 28520578
TI - Robust Antidepressant Effect Following Alternating Intravenous Racemic Ketamine
and Electroconvulsive Therapy in Treatment-Resistant Depression: A Case Report.
PMID- 28520581
TI - Reply to: Accuracy of Consecutive Fecal Calprotectin Measurements to Predict
Relapse in Inflammatory Bowel Disease Patients.
PMID- 28520580
TI - High Agreement Between Benchtop and Point-of-Care Dipcard Tests for Ethyl
Glucuronide.
PMID- 28520582
TI - Intramedullary Nailing for Pilon Nonunions.
AB - Nonunions are uncommon sequelae of tibial pilon fractures, but they can present a
challenging problem to the treating surgeon. Treatment strategies can range from
isolated bone grafting to revision plating depending on the type of nonunion and
patient factors. Here, we present our technique and clinical results for
intramedullary nailing of tibial pilon nonunions.
PMID- 28520579
TI - The Use of an Acellular Oxygen Carrier in a Human Liver Model of Normothermic
Machine Perfusion.
AB - BACKGROUND: Normothermic machine perfusion of the liver (NMP-L) is a novel
technique that preserves liver grafts under near-physiological conditions while
maintaining their normal metabolic activity. This process requires an adequate
oxygen supply, typically delivered by packed red blood cells (RBC). We present
the first experience using an acellular hemoglobin-based oxygen carrier (HBOC)
Hemopure in a human model of NMP-L. METHODS: Five discarded high-risk human
livers were perfused with HBOC-based perfusion fluid and matched to 5 RBC
perfused livers. Perfusion parameters, oxygen extraction, metabolic activity, and
histological features were compared during 6 hours of NMP-L. The cytotoxicity of
Hemopure was also tested on human hepatic primary cell line cultures using an in
vitro model of ischemia reperfusion injury. RESULTS: The vascular flow parameters
and the perfusate lactate clearance were similar in both groups. The HBOC
perfused livers extracted more oxygen than those perfused with RBCs (O2
extraction ratio 13.75 vs 9.43 % *10 per gram of tissue, P = 0.001). In vitro
exposure to Hemopure did not alter intracellular levels of reactive oxygen
species, and there was no increase in apoptosis or necrosis observed in any of
the tested cell lines. Histological findings were comparable between groups.
There was no evidence of histological damage caused by Hemopure. CONCLUSIONS:
Hemopure can be used as an alternative oxygen carrier to packed red cells in NMP
L perfusion fluid.
PMID- 28520583
TI - Focal Capillary Dropout Associated With Optic Disc Drusen Using Optical Coherence
Tomographic Angiography.
AB - Optic disc drusen may be a cause of visual field defects and visual loss. The
mechanism by which this occurs is unclear. We report a patient who developed
decreased vision in the right eye and was found to have a heavy burden of
superficial optic disc drusen. Optical coherence tomography (OCT) confirmed focal
retinal nerve fiber layer thinning that corresponded with the distribution of
drusen. OCT angiography, with superficial laminar segmentation, showed focal
capillary attenuation overlying the most prominent drusen. These findings
demonstrate alterations in the superficial retinal capillary network associated
with optic disc drusen.
PMID- 28520585
TI - The role of simulation and warm-up in minimally invasive gynecologic surgery.
AB - PURPOSE OF REVIEW: The purpose of the review is to update the reader on the
current literature and recent studies evaluating the role of simulation and warm
up as part of surgical education and training, and maintenance of surgical
skills. RECENT FINDINGS: Laparoscopic and hysteroscopic simulation may improve
psychomotor skills, particularly for early-stage learners. However, data are
mixed as to whether simulation education is directly transferable to surgical
skill. Data are insufficient to determine if simulation can improve clinical
outcomes. Similarly, performance of surgical warm-up exercises can improve
performance of novice and expert surgeons in a simulated environment, but the
extent to which this is transferable to intraoperative performance is unknown.
Surgical coaching, however, can facilitate improvements in performance that are
directly reflected in operative outcomes. SUMMARY: Simulation-based curricula may
be a useful adjunct to residency training, whereas warm-up and surgical coaching
may allow for maintenance of skill throughout a surgeon's career. These
experiences may represent a strategy for maintaining quality and value in a lower
volume surgical setting.
PMID- 28520584
TI - Eating disorders and bone metabolism in women.
AB - PURPOSE OF REVIEW: Eating Disorders are psychiatric disorders associated with a
high risk for low bone mineral density (BMD) and fractures. Low BMD is a
consequence of undernutrition, changes in body composition, and hormonal
alterations. This review summarizes recent findings regarding novel strategies
for assessing bone outcomes in patients with eating disorders, factors
contributing to altered bone metabolism, and possible therapeutic strategies.
RECENT FINDINGS: Emerging research in this field suggests that not only anorexia
nervosa, but also bulimia nervosa results in lower BMD compared to controls. To
date studies of bone structure, and all randomized controlled trials examining
the impact of various therapies on bone outcomes in anorexia nervosa, have
focused on adolescent girls and women. We discuss the impact of anorexia nervosa
on bone structure, and associations of resting energy expenditure, marrow adipose
tissue (including the ratio of saturated to unsaturated fat), and cold activated
brown adipose tissue with BMD and bone structure. Promising strategies for
treatment include physiological estrogen replacement (rather than oral
contraceptives) in adolescent girls with anorexia nervosa, and bisphosphonates,
as well as teriparatide, in adult women with anorexia nervosa. SUMMARY: Recent
data on (i) BMD and bone structure in adolescent girls and women with eating
disorders, (ii) factors that contribute to altered bone metabolism, and (iii)
randomized controlled trials reporting positive effects of physiologic estrogen
replacement, bisphosphonates and teriparatide on bone health, provide us with a
greater understanding of the impact of eating disorders on bone and novel
management strategies.
PMID- 28520587
TI - Complementary Roles of Nod2 in Hematopoietic and Nonhematopoietic Cells in
Preventing Gut Barrier Dysfunction Dependent on MLCK Activity.
AB - BACKGROUND: Crohn's disease (CD) pathogenesis is multifactorial involving genetic
and environmental factors. Loss of function mutations in the nucleotide
oligomerization domain 2 (NOD2) gene are the main genetic risk factor for CD.
Like patients with CD, Nod2 mice are characterized by an enhanced Th1 immune
response and a defective mucosal barrier function evidenced by increased
intestinal permeability. We previously showed that the latter is related to
hematopoietic Nod2 deficiency. Our aim was to explore the mechanisms by which
Nod2 expressed in the hematopoietic and in the nonhematopoietic compartments
interplay to control epithelial paracellular permeability. METHODS: Depletion of
CD4 T cells in Nod2 mice and treatments with inhibitors were conducted in
chimeric mice transplanted with bone marrow cells from Nod2-deficient donors into
Nod2-sufficient recipients or vice versa. Caco-2 cells overexpressing a NOD2 gene
which did or did not include a CD-associated polymorphism were treated with
inhibitors or siRNAs and cocultured with hematopoietic cells from Peyer's
patches. RESULTS: In vivo and in vitro Nod2 in hematopoietic cells regulates
epithelial paracellular permeability through cytokine production influencing
myosin light chain kinase (MLCK) activity. Indeed, tumor necrosis factor-alpha
and interferon-gamma secretion by CD4 T cells upregulated expression and activity
of epithelial MLCK leading to increased epithelial tight junction opening. When
stimulated by muramyl dipeptide, Nod2 in the nonhematopoietic compartment
normalized the permeability and T-cell cytokine secretion and regulated MLCK
activity. This MLCK regulation is mediated by TAK1 and RICK-dependent mechanisms.
CONCLUSIONS: Our study demonstrates how hematopoietic and nonhematopoietic Nod2
regulate intestinal barrier function, improving our knowledge on the mechanisms
involved in CD pathogenesis.
PMID- 28520586
TI - Clinical Course of Ulcerative Colitis After Liver Transplantation in Patients
with Concomitant Primary Sclerosing Cholangitis and Ulcerative Colitis.
AB - BACKGROUND: The natural history of ulcerative colitis (UC) after liver
transplantation (LT) for primary sclerosing cholangitis (PSC) remains ill
defined. This study aimed to evaluate the course of UC after LT for PSC. METHODS:
The course of UC, including the clinical colitis severity index, was evaluated in
patients with concomitant PSC and UC who received LT for PSC-induced end-stage
liver disease. A total of 167 (55.4%) patients with PSC had concurrent
inflammatory bowel disease (IBD). Of 159 cases of IBD that started before LT, 152
(95.5%) had UC and 7 (4.5%) had Crohn's disease. RESULTS: The mean duration of
patient follow-up after LT was 47.7 +/- 33.5 months. The simple clinical colitis
activity index scores after LT showed no change in 15.8% of patients, decreased
in 78.3%, and increased in 5.9%. Seventy-one (46.7%) patients required no change
in their specific UC treatment after LT, whereas 12 (7.9%) had to use more
aggressive treatments after LT. In 69 (45.4%) patients, treatment could be
tapered although not discontinued. Multiple logistic regression analysis
demonstrated that the duration of LT (odds ratio = 1.02; 95% confidence interval,
1.00-1.05, P = 0.03) was significantly associated with aggravation in the
clinical course of UC after LT. Posttransplant cyclosporine exposure (odds ratio
= 0.14; 95% confidence interval, 0.015-0.79, P = 0.028) and pretransplant body
weight (odds ratio = 0.81; 95% confidence interval, 0.71-0.93, P = 0.003)
demonstrated a protective effect. CONCLUSIONS: Although the clinical course of UC
remains unchanged or even improves in the majority of patients after LT, some may
experience an aggressive course. The type of immunosuppression after
transplantation can affect UC activity after LT. Cyclosporine may have some
protective effects post-LT.
PMID- 28520588
TI - Evaluation of the Quality of Semen and Sexual Function in Men with Inflammatory
Bowel Disease.
AB - BACKGROUND: Data on fertility rates and medication safety in men with
inflammatory bowel disease (IBD) are limited. The aim of this study was to
evaluate whether there is a seminal alteration in patients with IBD and, if so,
to evaluate the mechanisms that may play a role according to what has been
described in the literature. Its secondary aim was to evaluate the impact on male
sexual function of IBD. METHODS: Multicenter, cross-sectional, case series study
comparing men with IBD and control subjects. Semen analysis was performed
according to the recommendations of World Health Organization. The impact on male
sexual function was evaluated with the International Index of Erectile Function
questionnaire. RESULTS: On multivariate analysis, patients with Crohn's disease
had lower sperm concentrations compared with those with ulcerative colitis
(median [interquartile range], 34.5 [19.2-48] versus 70 [34.5-127.5], P = 0.02)
and lower seminal zinc levels (mean +/- SD, 1475 +/- 235 MUmol/L versus 2221 +/-
1123 MUmol/L, P = 0.04). Patients with Crohn's disease on anti-tumor necrosis
factor treatment had better progressive motility (mean +/- SD, 56.7 +/- 17.7
versus 35.1 +/- 22.1, P = 0.01) and sperm morphology (14.4 +/- 7.1 versus 7.6 +/-
4.9, P = 0.04) than those who were not on anti-tumor necrosis factor. Regarding
sexual function, no significant differences were found across patients with IBD
and control subjects. CONCLUSIONS: Men with Crohn's disease showed a trend toward
poorer semen quality than those with ulcerative colitis. Treatment with anti
tumor necrosis factor drugs does not seem to be associated with poor sperm
quality. In patients in clinical remission, male sexual function is not affected
by IBD.
PMID- 28520589
TI - Distance to Specialist Care and Disease Outcomes in Inflammatory Bowel Disease.
AB - BACKGROUND: Optimal treatment of inflammatory bowel disease (IBD) requires
specialized health care. Patients frequently travel long distances to obtain care
for IBD, which may hinder regular care and affect outcomes adversely. METHODS:
This study included patients with established Crohn's disease or ulcerative
colitis receiving care at a single referral center between January 2005 and
August 2016. Distance to our health care center from the zip code of residence
was determined for each patient and classified into quartiles. Our primary
outcome was need for IBD-related surgery with secondary outcomes being need for
biological and immunomodulator therapy. Logistic regression models adjusting for
relevant covariates examined the independent association between travel distance
and patient outcomes. RESULTS: Our study included 2136 patients with IBD (1197
Crohn's disease, 939 ulcerative colitis), among which just over half were women
(52%), and the mean age was 41 years. The mean distance from our hospital was
2.5, 8.8, 22.0, and 50.8 miles for the first (most proximal) through fourth (most
distant), respectively. We observed a statistically significant and meaningful
higher risk among patients in the most distant quartile in the need for
immunomodulator use (OR, 1.69; 95% CI, 1.29-2.22), biological therapy (OR, 2.19;
95% CI, 1.69-2.85), and surgery (OR, 2.44; 95% CI, 1.80-3.32). Differences
remained significant on multivariable analysis and by type of IBD. CONCLUSIONS:
Greater distance to referral health care center was associated with increased
risk for needing IBD-related surgery in patients with Crohn's disease or
ulcerative colitis.
PMID- 28520590
TI - Role of tyrosine kinase inhibitors in the treatment of pituitary tumours: from
bench to bedside.
AB - PURPOSE OF REVIEW: Treatment of aggressive pituitary tumours often yields
suboptimal control of the tumour and confers significant morbidity. Lactotroph
and corticotroph-derived tumours express ErbB receptors and ligands, and
mutations in ubiquitin-specific protease 8 (USP8), which alters epidermal growth
factor receptor (EGFR) degradation, have been implicated in Cushing disease
pathogenesis. EGFR tyrosine kinase inhibitor (TKI) therapy has emerged as a
potential new therapeutic approach for patients with aggressive prolactinomas and
Cushing disease. RECENT FINDINGS: Using EGFR or human epidermal growth factor
receptor 2-driven prolactin (PRL) promoters, transgenic mice develop large
tumours that respond to TKI inhibition. In human corticotroph primary cultures,
treatment with the pan-ErbB TKI canertinib as well as the EGFR TKI gefitinib
suppresses proopiomelanocortin mRNA. USP8 mutations, detected in up to two-thirds
of Cushing disease, may underlie the increase in EGFR signalling in these
tumours. Human prolactinomas have differential ErbB receptor expression
associated with aggressive behaviour and data from an ongoing clinical trial
suggest that resistant prolactinomas may respond to the EGFR TKI lapatinib.
SUMMARY: Preclinical and clinical models substantiate the role of the EGFR
pathway in corticotroph and lactotroph adenomas. Although further study is
needed, results to date suggest that targeting the ErbB pathway may be an
effective therapeutic approach for patients with aggressive pituitary tumours.
PMID- 28520591
TI - Stem cell therapy and its potential role in pituitary disorders.
AB - PURPOSE OF REVIEW: The pituitary gland is one of the key components of the
endocrine system. Congenital or acquired alterations can mediate destruction of
cells in the gland leading to hormonal dysfunction. Even though pharmacological
treatment for pituitary disorders is available, exogenous hormone replacement is
neither curative nor sustainable. Thus, alternative therapies to optimize
management and improve quality of life are desired. RECENT FINDINGS: An
alternative modality to re-establish pituitary function is to promote endocrine
cell regeneration through stem cells that can be obtained from the pituitary
parenchyma or pluripotent cells. Stem cell therapy has been successfully applied
to a plethora of other disorders, and is a promising alternative to hormonal
supplementation for resumption of normal hormone homeostasis. SUMMARY: In this
review, we describe the common causes for pituitary deficiencies and the advances
in cellular therapy to restore the physiological pituitary function.
PMID- 28520592
TI - Validation of the A&D UM-211 device for office blood pressure measurement
according to the European Society of Hypertension International Protocol revision
2010.
AB - The aim of this study was to define the accuracy of UM-211, an automated
oscillometric device for office use coupled to several cuffs for different arm
sizes, according to the International Protocol of the European Society of
Hypertension. The validation was performed in 33 individuals. Their mean age was
59.6+/-12.9 years, systolic blood pressure (BP) was 144.3+/-21.5 mmHg (range: 96
184 mmHg), diastolic BP was 86.8+/-18.5 mmHg (range: 48-124 mmHg), and arm
circumference was 30.2+/-4.3 cm (range: 23-39 cm). Four sequential readings were
taken by observers 1 and 2 using a double-headed stethoscope and a mercury
sphygmomanometer, whereas three BP readings were taken by the supervisor using
the test instrument. The differences between the readings provided by the device
and the mean observer measurements were calculated. Therefore, each device
measurement was compared with the previous and the next mean observer
measurement. The validation results fulfilled all the 2010 European Society of
Hypertension revision Protocol criteria for the general population and passed all
validation grades. On average, the device overestimated systolic BP by 1.7+/-2.4
mmHg and diastolic BP by 1.7+/-2.5 mmHg. These data show that the UM-211 device
coupled to several cuffs for different ranges of arm circumference met the
requirements for validation according to the International Protocol and can be
recommended for clinical use in the adult population. However, these results
mainly apply to the use of the 22-32 and the 31-45 cm cuffs.
PMID- 28520593
TI - Strengthening Health Systems to Provide Rehabilitation Services.
PMID- 28520594
TI - AmpliVue Is a Practical and Timely Test for the Detection of HSV From Keratitis
Specimens.
AB - OBJECTIVE: The laboratory diagnostic detection of herpes simplex virus (HSV) from
eye samples must be practical, timely, and definitive for appropriate therapy.
Although polymerase chain reaction (PCR) and/or cell culture can be definitive,
HSV results can be delayed. Enzyme Linked Virus Inducible System (ELVIS) is a
test that can provide results within 24 to 48 hr. We evaluated "AmpliVue HSV 1+2
Assay" as a molecular colorimetric test that can detect HSV (1 or 2) DNA within 1
hr. METHODS: Cornea/conjunctival samples were tested retrospectively with
AmpliVue against 53 true-positive and 20 true-negative specimens collected in
chlamydial transport medium. All clinical specimens were tested by cell culture
isolation, PCR, and ELVIS for routine patient care. RESULTS: The sensitivity of
AmpliVue against ocular samples that were both culture-positive and PCR-positive
was 84%. The specificity of AmpliVue was 100%. Only one clinical sample was HSV-2
positive, whereas all others tested positive for HSV-1. Based on PCR-positive and
cell culture-negative samples, AmpliVue (11 of 17) tested more positive than
ELVIS (0 of 17) (P=0.003, Fisher Exact). CONCLUSIONS: AmpliVue is moderately
sensitive and highly specific as a practical and timely diagnostic test for
detecting ocular HSV. Expertise is readily achieved and the test is
straightforward with easy interpretation. Negative AmpliVue testing must be
confirmed with PCR. AmpliVue has potential as an office-based diagnostic test.
PMID- 28520595
TI - Decreased Visual Acuity by an Irregular Corneal Posterior Surface After Repeat
Descemet Stripping Automated Endothelial Keratoplasty.
AB - PURPOSE: To investigate the impact of higher-order aberrations (HOAs) on visual
acuity after repeat Descemet stripping automated endothelial keratoplasty (DSAEK)
in the same eyes. METHODS: This retrospective comparative case series includes 23
patients who underwent DSAEK twice in the same eyes (46 DSAEK in total). We
evaluated the HOAs of the anterior and posterior corneal surfaces, and total
cornea using the Fourier analysis data from anterior segment optical coherence
tomography. Eyes were divided into one of the following groups, based on the
improvement and decline in the best-corrected visual acuity (BCVA) after repeat
DSAEK; group A: 12 eyes with an improvement >= 2 lines, group B: 12 eyes with a
decline <= 2 lines, and group C: 11 eyes with no change or change within 1 line.
RESULTS: The HOAs of the posterior surface in group B were significantly greater
than those of group A (P=0.028), whereas there were no significant differences in
the anterior surface and total corneal HOAs between groups A and B (P=0.12 and
0.08). There were no significant differences in the anterior and posterior
surface as well as total cornea HOAs between initial DSAEK and repeat DSAEK in
group C (P=0.87, 0.65, and 0.42). The postoperative BCVA had a significant
correlation with the HOAs of the anterior and posterior surfaces as well as the
total cornea (R=0.40, 0.46, and 0.53; P=0.01, 0.002, and 0.001). CONCLUSIONS:
Posterior corneal HOAs can have a negative influence on the visual acuity after
endothelial keratoplasty.
PMID- 28520596
TI - Fungal Keratitis Associated With Airborne Organic Debris and Soft Contacts
Lenses: Case Reports and Review of the Literature.
AB - OBJECTIVES: To report two cases of fungal keratitis in soft contact lens wearers
who were exposed to environmental mold. METHODS: Case reports, with review of the
relevant literature. RESULTS: Two otherwise healthy middle-aged women who were
soft contact lens wearers developed fungal keratitis about 1 week after heavy
exposure to environmental mold. Culture results showed Aspergillus from one
patient and the unusual combination of Trichoderma and Penicillium from the
other. Both were treated with topical natamycin, topical fluoroquinolone
antibiotic prophylaxis, and periodic ulcer debridement. After many weeks of
treatment, both ulcers healed with subsequent scarring. Because the ulcers were
located in the peripheral cornea in both cases, excellent final visual acuities
were achieved. Fungal keratitis cases like these are rarely seen at our referral
clinic, which is located in the temperate climate of northeastern Indiana.
CONCLUSIONS: In addition to the usual recommended contact lens care guidelines,
it may be prudent for eye care providers to warn patients against wearing their
contact lenses in situations likely to result in heavy exposure to organic matter
or, at the very least, to wear tight-fitting goggles for eye protection.
PMID- 28520597
TI - Key performance indicators' assessment to develop best practices in an Emergency
Medical Communication Centre.
AB - INTRODUCTION: Emergency Medical Communication Centre (EMCC) represents a pivotal
link in the chain of survival for those requiring rapid response for out-of
hospital medical emergencies. Assessing and grading the performance of EMCCs are
warranted as it can affect the health and safety of the served population.
OBJECTIVE: The aim of our work was to describe the activity on an EMCC and to
explore the associations between different key performance indicators. METHODS:
We carried out our prospective observational study in the EMCC of Nantes, France,
from 6 June 2011 to 6 June 2015. The EMCC performance was assessed with the
following key performance indicators: answered calls, Quality of Service 20 s
(QS20), occupation rate and average call duration. RESULTS: A total of 35 073 h
of dispatch activity were analysed. 1 488 998 emergency calls were answered. The
emergency call incidence varied slightly from 274 to 284 calls/1000 citizens/year
between 2011 and 2015. The median occupation rate was 35% (25-44). QS20 was
correlated negatively with the occupation rate (Spearman's rho: -0.78). The
structural equation model confirmed that the occupation rate was highly
correlated with the QS20 (standardized coefficient: -0.89). For an occupation
rate of 26%, the target value estimated by our polynomial model, the probability
of achieving a QS20 superior or equal to 95% varied between 56 and 84%.
CONCLUSION: The occupation rate appeared to be the most important factor
contributing towards the QS20. Our data will be useful to develop best practices
and guidelines in the field of emergency medicine communication centres.
PMID- 28520599
TI - Healing by Intention.
PMID- 28520602
TI - Medical Nutrition Therapy, Obesity Behavioral Therapy, and Smoking Cessation
Counseling Reimbursement Q & A's.
PMID- 28520598
TI - Imaging plus X: multimodal models of neurodegenerative disease.
AB - PURPOSE OF REVIEW: This article argues that the time is approaching for data
driven disease modelling to take centre stage in the study and management of
neurodegenerative disease. The snowstorm of data now available to the clinician
defies qualitative evaluation; the heterogeneity of data types complicates
integration through traditional statistical methods; and the large datasets
becoming available remain far from the big-data sizes necessary for fully data
driven machine-learning approaches. The recent emergence of data-driven disease
progression models provides a balance between imposed knowledge of disease
features and patterns learned from data. The resulting models are both predictive
of disease progression in individual patients and informative in terms of
revealing underlying biological patterns. RECENT FINDINGS: Largely inspired by
observational models, data-driven disease progression models have emerged in the
last few years as a feasible means for understanding the development of
neurodegenerative diseases. These models have revealed insights into
frontotemporal dementia, Huntington's disease, multiple sclerosis, Parkinson's
disease and other conditions. For example, event-based models have revealed finer
graded understanding of progression patterns; self-modelling regression and
differential equation models have provided data-driven biomarker trajectories;
spatiotemporal models have shown that brain shape changes, for example of the
hippocampus, can occur before detectable neurodegeneration; and network models
have provided some support for prion-like mechanistic hypotheses of disease
propagation. The most mature results are in sporadic Alzheimer's disease, in
large part because of the availability of the Alzheimer's disease neuroimaging
initiative dataset. Results generally support the prevailing amyloid-led
hypothetical model of Alzheimer's disease, while revealing finer detail and
insight into disease progression. SUMMARY: The emerging field of disease
progression modelling provides a natural mechanism to integrate different kinds
of information, for example from imaging, serum and cerebrospinal fluid markers
and cognitive tests, to obtain new insights into progressive diseases. Such
insights include fine-grained longitudinal patterns of neurodegeneration, from
early stages, and the heterogeneity of these trajectories over the population.
More pragmatically, such models enable finer precision in patient staging and
stratification, prediction of progression rates and earlier and better
identification of at-risk individuals. We argue that this will make disease
progression modelling invaluable for recruitment and end-points in future
clinical trials, potentially ameliorating the high failure rate in trials of,
e.g., Alzheimer's disease therapies. We review the state of the art in these
techniques and discuss the future steps required to translate the ideas to front
line application.
PMID- 28520603
TI - Does Negative-Pressure Wound Therapy for the Open Abdomen Benefit the Patient? A
Retrospective Cohort Study.
AB - OBJECTIVE: Negative-pressure wound therapy (NPWT) is the most modern and
sophisticated method of temporary abdominal closure. The aim of the study was to
determine the significant predictors for mortality in patients with NPWT.
SETTING: University Clinical Centre Maribor, Slovenia MATERIALS AND METHODS:: The
authors performed a retrospective cohort study of all patients treated with NPWT
between January 1, 2011, and December 31, 2014. RESULTS: In the univariate
analysis, the type of wound closure, more than 7 NPWT changes, the total days
with NPWT, and time to wound closure were significantly associated with death of
the patient. In the multivariate analysis, only the number of more than 7 NPWT
changes was found as a significant predictor for death (P = .038). CONCLUSIONS:
Negative-pressure wound therapy is a method of choice for the treatment of open
abdomen if there is a clear indication. However, clinicians should try all
measures to remove the NPWT system and close the abdomen as soon as possible
because prolonged use is associated with significantly higher mortality.
PMID- 28520604
TI - In Vitro Evaluation of Betafoam, a New Polyurethane Foam Dressing.
AB - BACKGROUND: A new polyurethane foam dressing impregnated with 3% povidone-iodine
(Betafoam; Genewell, Seoul, Korea) was recently developed based on the hypothesis
that its physical properties, including improved moisture-retention capacity and
antimicrobial activity, are at least as good as those achieved with the current
foam dressings that contain silver, but also associated with reduced cost and
cytotoxicity to host cells. The purpose of this in vitro study was to evaluate
the efficacy of Betafoam by comparing its physical properties, antimicrobial
activity, and cytotoxicity with those of 3 silver foam dressings (Allevyn-Ag
[Smith & Nephew, Hull, United Kingdom]; Mepilex-Ag [Molnlycke Health Care,
Gothenburg, Sweden]; and PolyMem-Ag [Ferris MFG Corp, Burr Ridge, Illinois]) used
worldwide. METHODS: This study measured each dressing's pore size, fluid
absorption time, fluid absorption capacity, fluid retention capacity,
antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa,
and cytotoxicity to mouse fibroblasts. RESULTS: Betafoam had the smallest pore
size, the fastest fluid absorption time, greatest fluid absorption, and best
retention capacities among the tested foam dressings. Antimicrobial activity was
not significantly different among the dressings. However, Betafoam also
demonstrated the lowest cytotoxicity to the fibroblasts. CONCLUSIONS: Betafoam
may result not only in desirable rapid regulation of exudation but also
antimicrobial activity with minimal cytotoxicity to host cells that are key
requirements for wound healing.
PMID- 28520605
TI - Reducing Postsurgical Wound Complications: A Critical Review.
AB - GENERAL PURPOSE: To provide information on risk factors for surgical site
infections (SSIs) and actions to mitigate that risk. TARGET AUDIENCE: This
continuing education activity is intended for surgeons, surgical teams,
physicians, physician assistants, nurse practitioners, and nurses with an
interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After
participating in this educational activity, the participant should be better able
to:1. Identify modifiable risk factors associated with the development of SSIs.2.
Select steps to mitigate the risks for and morbidity from SSIs. ABSTRACT: Given
the current reimbursement structure, the avoidance of a surgical site infection
(SSI) is crucial. Although many risk factors are associated with the formation of
an SSI, a proactive and interprofessional approach can help modify some factors.
Postoperative strategies also can be applied to help prevent an SSI. If an SSI
becomes a chronic wound, there are recommended guidelines and strategies that can
foster healing.
PMID- 28520606
TI - Quality Payment Program: Advancing Care Information Performance Category: Part 2.
PMID- 28520607
TI - Reducing Postsurgical Wound Complications: A Critical Review.
PMID- 28520608
TI - Choroideremia.
AB - PURPOSE OF REVIEW: Although much has been written to define the phenotype and
genotype of choroideremia (CHM), research continues to provide new insights that
serve to better understand its pathogenesis and the directions for potential
experimental therapies. RECENT FINDINGS: We would like to highlight new findings,
expanding the type of disease-causing mutations to include mutations in the CHM
promoter that will dramatically influence gene expression. Information derived
from careful phenotyping of patients points increasingly to the central role of
the retinal pigment epithelium as the key cell layer affected in the degenerative
process. Finally, we will review the current initiatives that are testing vector
mediated gene replacement approaches in humans, including our current
understanding of the likelihood of success by this approach. SUMMARY: Clinical
and basic vision science have benefited greatly by the active engagement of
patients with CHM in clinical research studies. The impetus for their involvement
in these studies has been generated by the initial results of safety from
subretinal injection of and AAV2.REP1 vector in humans. Follow-up studies in the
next few years are expected to show if this approach will modify disease
progression.
PMID- 28520609
TI - Fuchs Endothelial Corneal Dystrophy in a Child.
PMID- 28520610
TI - Candidates for inclusion in a universal antiretroviral regimen: dolutegravir.
AB - PURPOSE OF REVIEW: The review addresses the role of dolutegravir (DTG) in first
line therapy. In the era of test and treat, where United Nations AIDS Program and
WHO have set the ambitious targets of 90/90/90, new efficacious, well tolerated,
and simple therapeutic options are needed. RECENT FINDINGS: DTG has been tested
in large clinical trials in treatment-naive patients, showing noninferiority to
raltegravir and superiority compared with efavirenz and ritonavir-boosted
darunavir, respectively. The main features of DTG are reviewed in this study,
including efficacy, safety, high-resistance barrier, daily treatment schedule,
and coformulation as single-tablet regimen. Use of DTG in special populations is
also reviewed. Tolerability, with focus in neuropsychiatric disturbances is
discussed in particular. DTG has shown high efficacy level, tested in males and
females, has no limitations in patients with renal and/or hepatic impairment and
is available as single drug (to be combined with two nucleoside reverse
transcriptase inhibitors in fixed combinations) or as a single-tablet regimen
combined with abacavir and lamivudine. SUMMARY: DTG is an excellent candidate for
initial therapy in HIV-infected patients. If safety of DTG in pregnant women are
confirmed by ongoing studies, DTG might become the first option in WHO
antiretroviral guidelines.
PMID- 28520612
TI - Guidelines on the management of arterial hypertension and related comorbidities
in Latin America.
PMID- 28520611
TI - Treatment Outcomes of Third-line Antiretroviral Regimens in HIV-infected Thai
Adolescents.
AB - BACKGROUND: Efficacy and safety data of third-line antiretroviral (ARV) regimens
in adolescents are limited. METHODOLOGY: This study enrolled HIV-infected Thais
who were treated with third-line regimens consisting of darunavir/ritonavir
(DRV/r), etravirine (ETR), tipranavir/ritonavir or raltegravir. RESULTS: Fifty
four adolescents 2-17 years of age were enrolled from 8 sites and followed for 48
weeks. Reasons for switch were second-line failure (n = 44) and toxicity to
second-line regimens (n = 10). At switching to third-line ARV, the median age
(interquartile range) was 14.3 (12.4-15.4) years. Genotypes at time of second
line failure (n = 44) were M184V (77%), >=4 thymidine analogue mutations (25%),
non-nucleoside reverse transcriptase inhibitor-resistant associated mutation
(RAM) (80%), ETR-RAM score >=4 (14%), any lopinavir-RAM (59%) and >=1 major DRV
RAM (41%). The third-line regimens had a median of 4 (min-max, 4-6) drugs and
included ETR/DRV/r (43%), DRV/r (33%), ETR (17%), tipranavir/ritonavir (2%) or
raltegravir/DRV/r/ (4%). The median CD4 (interquartile range) increased from 16%
(12-21) at third-line switch to 21% (18-25) and 410 (172-682) to 607 (428-742)
cells/mm at 48 weeks (P < 0.001). HIV RNA declined from 3.9 (2.9-4.9) to 1.6 (1.6
3.0) log10 copies/mL (P < 0.001) and 33/50 (66%) had levels <50 copies/mL at 48
weeks. Seventeen (31%) had HIV-RNA >=1000 copies/mL; about half due to poor
adherence; genotyping in 13 of these adolescents revealed ETR-RAM score >=4 in 2
(15%) and >=1 major DRV-RAM in 7 (54%). CONCLUSIONS: Third-line ARV therapy was
well tolerated and resulted in virologic suppression in 70% of adolescents at 1
year. Poor adherence and limited ARV options are major problems in the long-term
management of adolescents with HIV.
PMID- 28520613
TI - Uric acid and blood pressure: exploring the role of uric acid production in The
Maastricht Study.
AB - OBJECTIVE: Accumulation of reactive oxygen species by increased uric acid
production has been suggested as a possible underlying mechanism for the
association between uric acid and high blood pressure (BP). We, therefore,
investigated the association between serum uric acid concentration and 24-h
urinary uric acid excretion, as proxy for uric acid production, with ambulatory
24-h blood pressure and hypertension. METHODS: Cross-sectional analyses were
conducted among 2555 individuals [52% men, mean age 60.0 +/- 8.2 years; 27% type
2 diabetes (by design)] from The Maastricht Study. Multivariable regression
analyses were performed to investigate the association of serum uric acid and 24
h urinary uric acid excretion with 24-h pulse pressure, 24-h mean arterial
pressure (MAP), and hypertension. RESULTS: After adjustment for traditional
hypertension risk factors, serum uric acid concentration (per SD of 81 MUmol/l)
was associated with higher 24-h MAP [beta 0.63 mmHg; confidence interval (CI)
0.27-1.00] and positively associated with hypertension (odds ratio 1.43; CI 1.27
1.61). Urinary uric acid excretion (per SD of 140 mg/day/1.73 m) was associated
with higher 24-h MAP (beta 0.79 mmHg; CI 0.46-1.12) and with hypertension (odds
ratio 1.13; CI 1.02-1.25). There was no significant association between serum and
24-h urinary uric acid excretion with 24-h pulse pressure. There was no
interaction with sex or age for the aforementioned associations. CONCLUSION:
Higher serum and urinary uric acid concentrations were associated with higher 24
h MAP and hypertension. These results suggest that serum and 24-urinary uric acid
concentrations, the latter as proxy for uric acid production are, independent of
each other, associated with BP and hypertension.
PMID- 28520614
TI - Incidence of Neurological Disorders Among HIV-Infected Individuals With Universal
Health Care in Taiwan From 2000 to 2010.
AB - OBJECTIVE: To determine the incidence of and factors associated with neurological
disorders in a large Taiwanese cohort of HIV-infected persons with free access to
highly active antiretroviral therapy (HAART). DESIGN: A retrospective population
based cohort study was conducted using the National Health Insurance Research
Database for the years 2000-2010. METHODS: We identified 13,316 HIV-positive
persons from 2000 through 2010. We used direct standardization to calculate age
adjusted and sex-adjusted incidence rates based on the 2000 World Health
Organization world standard population. Factors associated with neurological
disorders were analyzed using a Cox proportional hazards model. RESULTS: The
standardized incidence of neurological disorders among HIV-infected persons
increased from 22.16 per 1000 person-years in 2000 to 25.23 per 1000 person-years
in 2010. Cognitive disorders increased significantly from 0.36 per 1000 person
years in 2001 to 7.44 per 1000 person-years in 2010 (trend P < 0.001). The rate
of neurological disorders increased with age >=55 years [adjusted hazard ratios
(AHRs) 2.54, 95% confidence interval (CI): 1.89 to 3.40], hypertension (AHR 1.41,
95% CI: 1.12 to 1.76), substance abuse (AHR 1.65, 95% CI: 1.36 to 2.02),
opportunistic infection (AHR 1.76, 95% CI: 1.47 to 2.11), syphilis (AHR 1.27, 95%
CI: 1.10 to 1.47), and emergency department visits >5 (AHR 2.41, 95% CI: 1.96 to
2.97). The incidence of neurological disorders was negatively associated with
adherence to HAART (adherence >=85% AHR: 0.79, 95% CI: 0.64 to 0.97).
CONCLUSIONS: The rising incidence of cognitive disorders among HIV-positive
persons highlights the need to provide routine neurological evaluations at
clinical visits. Receiving HAART with adherence >=85% contributes to a reduced
risk of neurological disorders.
PMID- 28520617
TI - Statin Prescribing Practices in the Comprehensive Care for HIV-Infected Patients.
PMID- 28520616
TI - Brief Report: Pediatric Cancer Burden and Treatment Resources Within the
Pediatric IeDEA Consortium.
AB - INTRODUCTION: The incidence and treatment of cancer in HIV-infected children from
resource-limited settings has not been extensively studied. OBJECTIVES: Develop
and implement a cross-sectional survey to evaluate pediatric cancer burden,
diagnostic modalities in use, and treatment availability as perceived by HIV
clinic staff at regional International Epidemiology Databases to Evaluate AIDS
(IeDEA) sites. METHODS: IeDEA regional investigators developed a cross-sectional
clinical site survey which included questions on the numbers and types of
pediatric cancers observed, modalities used to treat identified cancers, and
treatment options available at individual sites in the Asia-Pacific, Latin
America, Central Africa, East Africa, West Africa, and Southern Africa regions.
RESULTS: Kaposi sarcoma, non-Hodgkin lymphoma, and Burkitt lymphoma were reported
by site personnel to be the most prevalent types of cancer in the pediatric HIV
population. Survey results indicate that access to comprehensive cancer treatment
modalities is very limited for children in these regions despite HIV care and
treatment sites reporting that they diagnose pediatric cancers. Responses also
showed that evaluating cancer in the pediatric HIV population is a challenge due
to a lack of resources and varying treatment availability within regions.
CONCLUSIONS: Further study is needed to increase our understanding of the
changing epidemiology of cancer in HIV-infected pediatric populations. Increased
financial and technical resources are critical to aid in the advancement of
health services to support treatment of these children in resource-constrained
settings.
PMID- 28520618
TI - Defining a Cutoff for Atazanavir in Hair Samples Associated With Virological
Failure Among Adolescents Failing Second-Line Antiretroviral Treatment.
AB - BACKGROUND: Adequate antiretroviral exposure is crucial to virological
suppression. We assessed the relationship between atazanavir hair levels with
self-reported adherence, virological outcomes, and the effect of a home-based
adherence intervention in HIV-infected adolescents failing second-line
antiretroviral treatment in Zimbabwe. METHODS: HIV-infected adolescents on
atazanavir/ritonavir-based second-line treatment for >=6 months with viral load
(VL) >1000 copies/mL were randomized to either standard care (control) or
standard care plus modified directly administered antiretroviral therapy
(intervention). Questionnaires were administered; VL and hair samples were
collected at baseline and after 90 days in each group. Viral suppression was
defined as <1000 copies/mL after follow-up. RESULTS: Fifty adolescents (10-18
years) were enrolled; 23 (46%) were randomized to intervention and 27 (54%) to
control. Atazanavir hair concentration <2.35 ng/mg (lower interquartile range for
those with virological suppression) defined a cutoff below which most
participants experienced virological failure. Male sex (P = 0.03), virological
suppression at follow-up (P = 0.013), greater reduction in VL (P = 0.006), and
change in average self-reported adherence over the previous month (P = 0.031)
were associated with adequate (>2.35 ng/mg) hair concentrations. Participants
with virological failure were more likely to have suboptimal atazanavir hair
concentrations (RR = 7.2, 95% CI: 1 to 51, P = 0.049). There were no differences
in atazanavir hair concentration between the arms after follow-up. CONCLUSIONS: A
threshold of atazanavir concentrations in hair (2.35 ng/mg), above which
virological suppression was likely, was defined for adolescents failing second
line atazanavir/ritonavir-based ART in Zimbabwe. Male sex and better self
reported adherence were associated with adequate atazanavir hair concentrations.
Antiretroviral hair concentrations may serve as a useful clinical tool among
adolescents.
PMID- 28520619
TI - Brief Report: Late Efavirenz-Induced Ataxia and Encephalopathy: A Case Series.
AB - BACKGROUND: WHO treatment guidelines recommend efavirenz in first-line
antiretroviral therapy (ART). Efavirenz commonly causes early transient
neuropsychiatric adverse events. We present 20 cases with severe encephalopathy
accompanied by ataxia due to efavirenz toxicity. METHODS: Consecutive HIV
infected adults taking efavirenz-containing ART admitted to Tshepong hospital,
Klerksdorp, South Africa with ataxia and encephalopathy were included in this
case series. RESULTS: We identified 20 women admitted to hospital with severe
ataxia. All received efavirenz-based ART for a median of 2 years. All had severe
ataxia and none had nystagmus. Eleven had features of encephalopathy. Median
weight was 34 kg [interquartile range (IQR): 29.7-35.3]; median CD4 count 299
cells/mm (IQR: 258-300) and most (18 of 19) were virally suppressed. Eight
patients had a record of prior weights and 7 of 8 showed significant weight loss
with a median weight loss of 10.8 kg (IQR: 8-11.6). All cases had plasma
efavirenz assays, 19 were supratherapeutic (more than twice the upper level of
therapeutic range), and 15 had concentrations above the upper limit of assay
detection. Ataxia resolved after withdrawal of efavirenz at a median time of 2
months (IQR: 1.25-4) and recurred in 2 of 3 patients when rechallenged.
Admissions before diagnosis were frequent with 10 cases admitted previously.
Three women died. CONCLUSIONS: Efavirenz toxicity may present with severe
reversible ataxia often with encephalopathy years after its initiation, likely in
genetic slow metabolizers. We recommend that patients whose weight is <40 kg
receive lower doses of efavirenz and that therapeutic drug monitoring be
considered, and efavirenz stopped in patients presenting with ataxia. Eight
patients had a record of prior subsequent weights and 7 of 8 showed significant
weight loss gain; median gain of 10.8 kg (IQR: 8-11.6).
PMID- 28520620
TI - (-)-Epigallocatechin-3-gallate ameliorates memory impairment and rescues the
abnormal synaptic protein levels in the frontal cortex and hippocampus in a mouse
model of Alzheimer's disease.
AB - (-)-Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenolic extract
in green tea and it has attracted increasing attention for its multiple bioactive
effects. However, the mechanisms by which EGCG exerts its neuroprotective actions
in Alzheimer's disease (AD) are presently lacking. In the present study, a
sporadic AD transgenic mouse model known as senescence-accelerated mouse prone 8
(SAMP8) was used to investigate whether oral administration of EGCG could improve
recognition and memory function through reduction of amyloid beta (Abeta) and tau
hyperphosphorylation. We also investigated the effects of chronic EGCG treatment
on the synaptic dysfunction in the frontal cortex (FC) and the hippocampus (Hip)
of AD mice. The results showed that long-term oral consumption of EGCG at a
relatively high dose (15 mg/kg) improved memory function in SAMP8 mice in the Y
maze and Morris water maze. The levels of Abeta1-42 and BACE-1 in FC and Hip were
significantly reduced by EGCG treatment. EGCG treatment also prevented the
hyperphosphorylation of tau and reversed the decreased synaptic protein marker
synaptophysin and postsynaptic density protein 95 in FC and Hip of SAMP8 mice.
The present study suggests that long-term oral consumption of EGCG ameliorates
impairments in spatial learning and memory and rescues the reduction in synaptic
proteins observed in an AD mouse model. Thus, EGCG may represent a novel
candidate agent for the treatment of neurodegenerative diseases.
PMID- 28520622
TI - Perilesional Reorganization in a Patient With Brain Tumor.
PMID- 28520615
TI - Increased Risk of Myocardial Infarction in HIV-Infected Individuals in North
America Compared With the General Population.
AB - BACKGROUND: Previous studies of cardiovascular disease (CVD) among HIV-infected
individuals have been limited by the inability to validate and differentiate
atherosclerotic type 1 myocardial infarctions (T1MIs) from other events. We
sought to define the incidence of T1MIs and risk attributable to traditional and
HIV-specific factors among participants in the North American AIDS Cohort
Collaboration on Research and Design (NA-ACCORD) and compare adjusted incidence
rates (IRs) to the general population Atherosclerosis Risk in Communities (ARIC)
cohort. METHODS: We ascertained and adjudicated incident MIs among individuals
enrolled in 7 NA-ACCORD cohorts between 1995 and 2014. We calculated IRs,
adjusted incidence rate ratios (aIRRs), and 95% confidence intervals of risk
factors for T1MI using Poisson regression. We compared aIRRs of T1MIs in NA
ACCORD with those from ARIC. RESULTS: Among 29,169 HIV-infected individuals, the
IR for T1MIs was 2.57 (2.30 to 2.86) per 1000 person-years, and the aIRR was
significantly higher compared with participants in ARIC [1.30 (1.09 to 1.56)]. In
multivariable analysis restricted to HIV-infected individuals and including
traditional CVD risk factors, the rate of T1MI increased with decreasing CD4
count [>=500 cells/MUL: ref; 350-499 cells/MUL: aIRR = 1.32 (0.98 to 1.77); 200
349 cells/MUL: aIRR = 1.37 (1.01 to 1.86); 100-199 cells/MUL: aIRR = 1.60 (1.09
to 2.34); <100 cells/MUL: aIRR = 2.19 (1.44 to 3.33)]. Risk associated with
detectable HIV RNA [<400 copies/mL: ref; >=400 copies/mL: aIRR = 1.36 (1.06 to
1.75)] was significantly increased only when CD4 was excluded. CONCLUSIONS: The
higher incidence of T1MI in HIV-infected individuals and increased risk
associated with lower CD4 count and detectable HIV RNA suggest that early
suppressive antiretroviral treatment and aggressive management of traditional CVD
risk factors are necessary to maximally reduce MI risk.
PMID- 28520621
TI - Outbreaks in the adult ICUs.
AB - PURPOSE OF REVIEW: Infectious disease outbreaks in the critical care setting are
common and serious consequence. This article reviews and summarizes recent
outbreaks in the adult ICUs. RECENT FINDINGS: Outbreaks of multidrug-resistant
bacteria, fungi, and emerging viruses in ICUs from different countries are
common. Outbreak investigation relies on epidemiologic methods, microbiologic
studies, and molecular typing methods. Overuse of antibiotics, gaps in
implementing infection prevention measures, and contaminated environment are
common causes of ICU outbreaks. ICU staff awareness of and preparedness for such
outbreaks are crucial for outbreak prevention and control. Specific infection
control measures vary according to outbreak transmission mode and cause. SUMMARY:
Outbreaks remain a significant threat to healthcare systems. Proper
implementation of infection prevention practices and judicious use of antibiotics
are needed for outbreak prevention in adult ICUs. Surveillance, proper outbreak
investigation, adherence to infection prevention and control measures, and
thorough disinfection of contaminated areas are required to successfully manage
outbreaks.
PMID- 28520623
TI - Subcrestal Iliac-Screw: A Technical Note Describing a Free Hand, In-line, Low
Profile Iliac Screw Insertion Technique to Avoid Side-connector Use and Reduce
Implant Complications.
AB - STUDY DESIGN: Case-series. OBJECTIVE: To report our modified iliac-screw
insertion technique and its clinical outcomes. SUMMARY OF BACKGROUND DATA: Iliac
screws are one of the preferred methods for modern spinopelvic-fixation. However,
the technique is not without complications, predominantly because of iliac-screw
head prominence, leading to pain and revisions. Conventional iliac-screw entry
point is sited superficially at the posterior-superior-iliac-spine (PSIS)
contributing to screw-head prominence. We propose a more low-profile, subcrestal
entry point that is more medial and inferior to the PSIS at the medial wall of
the iliac crest, lying underneath the crest but above the sacroiliac joint. This
position keeps the screw-head low profile and in-line with proximal
instrumentation to ease rod engagement. METHODS: Ten consecutive patients who
underwent spinal deformity correction surgery using the modified iliac-screw
entry point fixations were enrolled. Clinical, radiological, and surgical
parameters were reviewed. RESULTS: Five males and five females with average age
of 66 years and average follow up of 29 months were reviewed. Mean preoperative
Cobb angle and C7-SVA were 32.1 degrees and 10.3 cm, respectively. Surgical
indication was progressive deformity and neurogenic claudication in eight cases
and fracture in two cases. Twenty noncannulated, polyaxial iliac-screws with
median dimension of 7.5 x 75 mm were inserted free hand. Bilateral S1 screws were
used in all except two cases. Only five out of 16 iliac-screws with concomitant
S1 screws needed side-connectors. At the last follow up only one iliac-screw head
was felt to be prominent but without pain in a Parkinson's patient. None of the
10 patients had cases of revision, breakages, or sacroiliac pain. CONCLUSION:
Subcrestal iliac-screw insertion is feasible, safe, and has the potential to
reduce screw-head complications and avoid the use of side-connectors, lowering
construct complexity and cost. The technique has the advantage of both the low
profile S2 alar iliac screw and the ease of free-hand insertion of the
traditional iliac-screw. LEVEL OF EVIDENCE: 4.
PMID- 28520624
TI - Cardiac Rehabilitation Outcomes by Ethnocultural Background: RESULTS FROM THE
CANADIAN CARDIAC REHAB REGISTRY.
AB - BACKGROUND: Patients of diverse ethnocultural backgrounds are underrepresented
among participants and, hence, little is known about their outcomes. The
objectives of this study were to compare cardiac rehabilitation (CR) utilization,
cardiovascular risk factor reduction (blood pressure, lipids, anthropometrics),
and functional capacity between white and ethnocultural minority patients
participating in CR across Canada. METHODS: The study was a retrospective,
observational cohort study using the Canadian Cardiac Rehab Registry (CCRR).
Participants from an ethnocultural minority (n >= 25) were propensity-matched to
white participants based on sociodemographic and clinical characteristics. CR
outcomes were compared. RESULTS: In the CCRR, 3848 (53.8%) participants had an
ethnocultural background reported. Of those, whites (n = 3630) and South Asians
(n = 26), Southeast Asians (n = 45), and Arab/West Asians (n = 37) minorities had
sufficient representation in the registry to be analyzed. In the matched sample,
364 (97.1%) participants completed a discharge assessment. Southeast Asian
participants adhered to (96.5%, P = .02) and completed (88.2%, P = .02) CR more
often than white participants (90.2% and 55.6%, respectively). Southeast Asian
participants had significantly lower diastolic blood pressure (P = .002) at CR
discharge than matched white participants. No other differences in outcomes or
functional capacity were observed. CONCLUSIONS: Ethnocultural minorities make up
a small proportion of CR participants in Canada. However, when they do
participate, they achieve similar CR outcomes compared with white participants.
CR programs should seek to ensure ethnoculturally diverse patients are referred
to their programs and ensure their programs are culturally sensitive to the needs
of the preponderant ethnocultural groups in their catchment areas.
PMID- 28520626
TI - MULTIMODAL IMAGING OF ACUTE EXUDATIVE POLYMORPHOUS VITELLIFORM MACULOPATHY WITH
OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY AND ADAPTIVE OPTICS SCANNING LASER
OPHTHALMOSCOPY.
AB - PURPOSE: To report a case of acute exudative polymorphous vitelliform maculopathy
including the findings of optical coherence tomography angiography and adaptive
optics scanning laser ophthalmoscopy. METHODS: Findings on clinical examination,
color fundus photography, spectral-domain optical coherence tomography, infrared
reflectance, autofluorescence, optical coherence tomography angiography, and
adaptive optics scanning laser ophthalmoscopy. RESULTS: A 54-year-old white man
with no significant medical history and history of smoking presented with
bilateral multiple serous and vitelliform detachments consistent with acute
exudative polymorphous vitelliform maculopathy. Extensive infectious,
inflammatory, and malignancy workup was negative. Spectral-domain optical
coherence tomography showed thickened, hyperreflective ellipsoid zone, subretinal
fluid, and focal as well as diffuse subretinal hyperreflective material
corresponding to the vitelliform lesions. Optical coherence tomography
angiography showed normal retinal and choroidal vasculature, whereas adaptive
optics scanning laser ophthalmoscopy showed circular focal "target" lesions at
the level of the photoreceptors in the area of foveal detachment. CONCLUSION:
Multimodal imaging is valuable in evaluating patients with acute exudative
polymorphous vitelliform maculopathy.
PMID- 28520625
TI - The Relationship Between Weather and Objectively Measured Physical Activity Among
Individuals With COPD.
AB - PURPOSE: Although daily variation in weather impacts physical activity (PA)
levels among relatively healthy individuals, it is largely unknown whether this
relationship occurs for those living with chronic obstructive pulmonary disease
(COPD). The purpose of this study was to examine how daily variation in
temperature, rain, and snow is related to objectively measured PA among patients
with COPD, and whether demographic or clinical characteristics moderate these
relationships. METHODS: Patients with COPD completed a questionnaire and wore a
pedometer for 7 days at baseline, end of pulmonary rehabilitation (PR), and 3 and
9 months after completing PR (28 days in total). RESULTS: Hierarchal linear
modeling showed that daily mean temperature and total daily rainfall, but not
snowfall, independently predicted steps/day, controlling for demographic and
clinical covariates in 189 patients in PR. Specifically, an increase of 10
degrees C translates into 316 more steps (6.6% of mean steps/day) whereas a
rainfall of 10 mm translates to 175 less steps (3.6% of mean steps/day).
Furthermore, those with higher income had more steps/day on warmer days.
CONCLUSIONS: These results add to converging evidence that weather plays an
important role in determining PA among individuals with COPD.
PMID- 28520627
TI - POSTERIOR SCLERAL MELANOCYTOSIS: A NOVEL FUNDUS FINDING MASQUERADING AS A
CHOROIDAL NEVUS.
AB - PURPOSE: To report a case of "posterior scleral melanocytosis," a pigmented
lesion of the posterior sclera that clinically resembles a flat choroidal nevus.
METHODS: Case report of a patient with posterior scleral melanocytosis.
Multimodal imaging, including swept source optical coherence tomography, was used
to demonstrate the scleral location of the pigmented lesion and to distinguish
its features from a typical choroidal nevus present in the same eye. RESULTS: An
86-year-old woman was seen for regular follow-up for neovascular age-related
macular degeneration in her right eye and 2 pigmented lesions in her left eye,
both presumed to be choroidal nevi. Anterior segment examination showed no
evidence of ocular or dermal melanocytosis. Optical coherence tomography of the
pigmented lesion in the left eye showed two distinct patterns. One lesion showed
hyperreflectivity within the choroidal tissue associated with posterior
shadowing, whereas the second lesion showed normal choroidal reflectivity with
hyperreflectivity confined to the inner sclera associated with marked posterior
shadowing. CONCLUSION: To the authors' knowledge, this is the first report of
posterior scleral melanocytosis, a pigmented fundus lesion confined to the inner
sclera. The need for high-penetrance optical coherence tomography to
differentiate these lesions from a typical choroidal nevus may explain why this
entity has not been previously described. The true nature of this entity will
ultimately require histopathologic study.
PMID- 28520628
TI - Impact of Perioperative Blood Transfusion on Survival Among Women With Breast
Cancer.
PMID- 28520629
TI - Blepharoplasty Effect on a Described Algorithmic Approach to External Ptosis
Repair: Is It Time for Unbundling?
AB - PURPOSE: To investigate the effects of performing a previously described
algorithmic levator resection for involutional ptosis with a blepharoplasty
instead of through a small incision. METHODS: Eyelids with involutional ptosis
and normal levator function were included in the study. An upper blepharoplasty
was performed first. An external levator resection was then performed based on a
described technique involving 2 mm resection of aponeurosis for 1 mm of desired
lift, consistent tension on the aponeurosis between surgical cases, and
standardized suture placement. RESULTS: Forty-one eyelids of 25 patients were
included. Mean postoperative margin to reflex distance 1 (MRD1) was 2.98 mm,
which was significantly higher than preoperative MRD1 (0.67 mm), but lower than
the predetermined goal MRD1 (3.35 mm). Eight eyelids did not meet primary outcome
of MRD1 within 1 mm of goal MRD1, with 5 undercorrections. There was no
difference between the postoperative MRD1 compared with the same ptosis technique
performed through a small incision only, but there were more intraoperative
suture adjustments and fewer eyelids meeting the primary outcome when a
concurrent blepharoplasty was performed. CONCLUSIONS: The addition of
blepharoplasty with a previously described algorithmic approach external levator
resection has an 80% success rate in achieving the primary outcome. When compared
with a small-incision ptosis repair, concurrent blepharoplasty results in a less
predictable outcome and an increased need for intraoperative adjustment.
Performing an algorithmic technique for external levator resection with a
blepharoplasty has less predictable outcomes, which raises the question of
separating the procedures to improve patient care.
PMID- 28520630
TI - Diagnostic Yield of Routine Electroencephalography With Concurrent Video
Recording in Detecting Interictal Epileptiform Discharges in Relation to Reasons
for Request: A Prospective Study of 1,080 Video-Electroencephalograms.
AB - PURPOSE: The aim of this study was to prospectively analyze the sensitivity and
specificity of routine electroencephalography with concurrent video recording
(vEEG) in relation to the reasons for requesting the test and to investigate when
routine vEEG should be requested. METHODS: We prospectively analyzed 1,080
consecutive vEEGs performed between April 2015 and April 2016. The requests for
vEEG were classified as requests with a low suspicion of epilepsy (syncope,
confusion or delirium, suspicion of psychogenic nonepileptic seizures, and
paroxysmal focal neurological deficit) or requests with a high suspicion of
epilepsy (first clinical seizure, suspected status epilepticus, follow-up study
of a patient with epilepsy, and acute symptomatic seizures). Predominant vEEG
findings (ictal and interictal epileptiform activities, diffuse, or focal slowing
and triphasic waves) were analyzed, and sensitivity and specificity [ZERO WIDTH
SPACE][ZERO WIDTH SPACE]values calculated. RESULTS: The most common indication
for vEEG was a follow-up study of patients with epilepsy (38%), followed by first
clinical seizure (19.3%) and suspected status epilepticus (11%). The respective
specificity and sensitivity values were 93% and 58% for 235 vEEGs performed in
children/adolescents (<=18 years), 95% and 40% for 533 vEEGs performed in adults
(>18 <= 65 years), and 93% and 39% for 312 vEEGs performed in older adults (>65
years). Twenty-four patients with false-positive paroxysms had a clinical
diagnosis of confusional state or paroxysmal focal neurological deficit.
Neurologists and neuropediatricians with experience in managing epilepsy had
higher specificity values than general neurologists or physicians (P = 0.012).
CONCLUSIONS: In our series, vEEG abnormalities were mainly observed in patients
with clinical findings highly suggestive of epilepsy. In confusional states, and
paroxysmal focal neurological deficit vEEG could be indicated.
PMID- 28520631
TI - Operculo-Insular Epilepsy: Scalp and Intracranial Electroencephalographic
Findings.
AB - PURPOSE: Operculo-insular seizures are heterogeneous and may resemble seizures
originating from the temporal, frontal, or parietal lobe. Although surface and
invasive EEG recordings are often necessary to detect operculo-insular seizures,
electrophysiological features of operculo-insular epilepsies remain poorly
characterized. This study describes the EEG findings of patients with operculo
insular epilepsy. METHODS: We reviewed electrophysiological data of all patients
(n = 9) with operculo-insular seizures revealed by intracranial EEG and for whom
operculo-insular epilepsy was confirmed by good seizure outcome after resective
or radiosurgery at our center between 2005 and 2013. Patients were divided
according to whether their seizure focus involved the anterior (group 1; n = 4)
or posterior (group 2; n = 5) portion of the insula. RESULTS: Interictal scalp
EEG was lateralizing and showed distinct topographical spike patterns between
groups: frontal and temporal in group 1, temporal in group 2. Intracranial
recordings showed abundant spikes limited to the operculo-insular region or
involving distant areas in the frontal/temporal (group 1) and temporal/parietal
lobes (group 2). Ictal intracranial EEG revealed discharges limited to the insula
or simultaneously involving extrainsular contacts at onset, notably the
orbitofrontal cortex (group 1) and the frontal and parietal opercula (group 2),
and propagating to the frontal and temporal lobes in group 1 and to parietal and
temporal lobes in group 2. CONCLUSIONS: Spike distribution and seizure
propagation in operculo-insular epilepsy follows an anterior-to-posterior pattern
mirroring an anterior or posterior insular focus localization. When presented
with frontal and/or temporal epileptiform abnormalities, an operculo-insular
focus should be considered.
PMID- 28520632
TI - Disruption of Brain-Heart Coupling in Sepsis.
AB - PURPOSE: To investigate heart rate and EEG variability and their coupling in
patients with sepsis and determine their relationship to sepsis severity and
severity of sepsis-associated brain dysfunction. METHODS: Fifty-two patients with
sepsis were prospectively identified, categorized as comatose (N = 30) and
noncomatose (N = 22), and compared with 11 control subjects. In a 30-minute EEG
and electrocardiogram recording, heart rate variability and EEG variability
(measured by the variability of relative power in a modified alpha band = RAP)
and their coupled oscillations were quantified using linear (least-square
periodogram and magnitude square coherence) and nonlinear (Shannon entropy and
mutual information) measures. These measures were compared between the three
groups and correlated with outcome, adjusting for severity of sepsis. RESULTS:
Several measures of heart rate variability and EEG variability and of their
coupled oscillations were significantly lower in patients with sepsis compared
with controls and correlated with outcome. This correlation was not independent
when adjusting for severity of sepsis. CONCLUSIONS: Sepsis is associated with
lower variability of both heart rate and RAP on EEG and reduction of their
coupled oscillations. This uncoupling is associated with the severity of
encephalopathy. Combined EEG and electrocardiogram monitoring may be used to gain
insight in underlying mechanisms of sepsis and quantify brainstem or thalamic
dysfunction.
PMID- 28520633
TI - Insular Cortex Surgery for the Treatment of Refractory Epilepsy.
AB - Focal epilepsy originating from the insular cortex is rare. One reason is the
small amount of cortical tissue compared with other lobes of the brain. However,
the incidence of insular epilepsy might be underestimated because of diagnostic
difficulties. The semiology and the surface EEG are often not meaningful or even
misleading, and elaborated imaging might be necessary. The close connections of
the insular cortex with other potentially epileptogenic areas, such as the
temporal lobe or frontal/central cortex, is increasingly recognized as possible
reason for failure of epilepsy surgery for temporal or extratemporal seizures.
Therefore, some centers consider invasive EEG recording of the insular cortex not
only in case of insular epilepsy but also in other focal epilepsies with
nonconclusive results from the presurgical work-up. The surgical approach to and
resection of insular cortex is challenging because of its deep location and
proximity to highly eloquent brain structures. Over the last decades, technical
adjuncts like navigation tools, electrophysiological monitoring and
intraoperative imaging have improved the outcome after surgery. Nevertheless,
there is still a considerable rate of postoperative transient or permanent
deficits, in some cases as unavoidable and calculated deficits. In most of the
recent series, seizure outcome was favorable and comparable with extratemporal
epilepsy surgery or even better. Up to now, the data volume concerning long-term
follow-up is limited. This review focusses on the surgical challenges of
resections to treat insular epilepsy, on prognostic factors concerning seizure
outcome, on postoperative deficits and complications. Moreover, less invasive
surgical techniques to treat epilepsy in this highly eloquent area are
summarized.
PMID- 28520634
TI - Associations Between Parental Factors and Child Diabetes-Management-Related
Behaviors.
AB - OBJECTIVE: Adherence to diabetes-management regimens in children requires
teamwork and consistency from both parents and children. This study investigated
a mediational model developed to understand the relationship between different
modifiable parent factors influencing child diabetes-related behaviors. METHODS:
We recruited 186 parents of children aged 2 to 10 years with Type 1 diabetes to
complete self-report questionnaires on child diabetes behavior, parental self
efficacy with managing the child's behavior, parent diabetes self-efficacy,
parent adjustment, condition management effort, parent perception of their
diabetes knowledge, and parenting behavior. We used structural equation modeling
in AMOS to test our hypothesized model of interrelationships between variables
associated with child diabetes behavior. RESULTS: The hypothesized model provided
good fit to the data. We found that parent perception of low levels of diabetes
knowledge and higher levels of condition management effort, and parent adjustment
difficulties were associated with lower parental self-efficacy with diabetes
management. This was further linked with lower levels of parental self-efficacy
with managing their child's diabetes behavior, and consequently, higher extent of
child diabetes behavior problems. Contrary to our expectations, we did not find a
significant effect of parenting behavior on child diabetes behavior problems,
either directly or indirectly via parent self-efficacy for managing child's
behavior. CONCLUSION: Our findings shed light on the mechanisms through which
different parenting factors interact and are associated with diabetes behavior in
children. These factors can be targeted through parenting interventions to
improve child's cooperation with diabetes-management tasks and reduce barriers to
effective management.
PMID- 28520636
TI - Commentary on "Counterbalanced Comparison of the Bayley Scales of Infant
Development-II and -III at 18 to 22 Months Corrected Age".
PMID- 28520635
TI - Decreasing Disparities in Child Development Assessment: Identifying and
Discussing Possible Delays in the Special Supplemental Nutrition Program for
Women, Infants, and Children (WIC).
AB - OBJECTIVE: To assess how staff at the Special Supplemental Nutrition Program for
Women, Infants, and Children (WIC) address potential developmental delays and
parent developmental concerns in children <5 years. METHODS: A Web-based survey
of Oregon WIC staff in nonadministrative roles assessed staff interactions with
parents regarding concerning child development/behavior, perceptions of
connectedness with local developmental resources, and knowledge of typical child
development. RESULTS: Staff (N = 153) responses indicated knowledge of typical
child development, frequent interactions with families about child development,
and frequent noticing of developmental concerns. However, most staff reported
being less than very well connected to developmental resources. Open-ended
responses suggested that staff frequently make direct referrals to early
intervention, public health nurses, and others who can further assess
developmental concerns. CONCLUSION: Although it is outside the primary scope of
their work, developmental and behavioral concerns are frequently raised and
addressed by WIC staff. Findings suggest that strengthening the existing referral
processes and enhancing continuity of care between WIC and developmental
providers may improve child outcomes and reduce disparities.
PMID- 28520637
TI - Clinical experience of stereotactic radiosurgery at a linear accelerator for
intraocular melanoma.
AB - Long-term results with linear accelerator LINAC-based stereotactic radiosurgery
for intraocular uveal malignant melanoma were assessed. A retrospective study was
carried out of patients with uveal melanoma after a 1-day session stereotactic
radiosurgery at LINAC in Slovakia. In the period 2001-2015, a group of 150
patients with uveal melanoma (139 choroidal melanoma, 11 ciliary body melanoma)
was treated. The median tumor volume at baseline was 0.5 cm (with range from 0.2
to 1.6 cm). Tumors ranged in size from 2.4 to 20.8 mm in basal diameter and from
2.0 to 18.3 mm in thickness. The therapeutic dose was 35.0 Gy by 99% of dose
volume histogram. Older age at treatment was correlated with the largest basal
tumor diameter, tumor thickness, and TNM stage. The survival after stereotactic
irradiation was 96% in 1 year, 93% in 2 years, 84% in 5 years, 80% in 7 years,
and 53% in 11 years. In 20 (13.3%) patients, secondary enucleation was necessary
because of complications (secondary glaucoma). Enucleation-free interval ranged
from 1 to 6 years. The median age at death was lower (65.7 years) for patients
who died from metastatic disease than for those who died from any other cause
(75.0 years). Survival rates at 5-year intervals and the need for secondary
enucleation because of complications after linear accelerator irradiation are
comparable to other techniques.
PMID- 28520638
TI - EFFECTS OF INTRAVITREAL RANIBIZUMAB AND BEVACIZUMAB ON THE RETINAL VESSEL SIZE IN
DIABETIC MACULAR EDEMA.
AB - PURPOSE: The goal of this study was to assess the effects of a single injection
of intravitreal ranibizumab (RAN) or bevacizumab (BEV) on the retinal vessel size
in eyes with diabetic macular edema. MATERIALS AND METHODS: In total, 32 patients
were enrolled in the RAN group, and 30 patients were included in BEV group. Each
of these groups was also subdivided into two others groups: a study group and a
control group. The study groups were composed of the injected eyes, whereas the
noninjected fellow eyes served as the control groups. The patients underwent
complete ophthalmic examinations, including optical coherence tomography and
fundus fluorescein angiography, and the primary outcome measures included the
central retinal artery equivalent, central retinal vein equivalent, and artery-to
vein ratio. RESULTS: In the RAN study group (n = 32), the preinjection mean
central retinal artery equivalent (175.42 MUm) decreased to 169.01 MUm after 1
week, and to 167.47 MUm after 1 month (P < 0.001), whereas the baseline central
retinal vein equivalent (235.29 MUm) decreased initially to 219.90 MUm after 1
week, and to 218.36 MUm after 1 month (P < 0.001). In the BEV study group (n =
30), the preinjection central retinal artery equivalent (150.21 MUm) decreased to
146.25 MUm after 1 week, and to 145.89 MUm after 1 month (P < 0.001); whereas the
baseline central retinal vein equivalent (211.87 MUm) decreased initially to
204.59 MUm after 1 week and was 205.24 MUm after 1 month (P < 0.001). The
preinjection artery-to-vein ratio values changed significantly (P = 0.001) after
1 week and after 1 month in the RAN group, but no significant alteration in the
artery-to-vein ratio was observed in the BEV group (P = 0.433). In both the RAN
(n = 32) and BEV (n = 30) control groups, none of the 3 parameters changed
throughout the study period, when compared with the baseline. CONCLUSION: The
results of this study showed that both RAN and BEV injections significantly
constricted the retinal blood vessel diameters.
PMID- 28520639
TI - WRINKLED VASCULARIZED RETINAL PIGMENT EPITHELIUM DETACHMENT PROGNOSIS AFTER
INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY.
AB - BACKGROUND/PURPOSE: Neovascular age-related macular degeneration (nAMD) is
frequently associated with vascularized pigment epithelial detachment (v-PED). We
observed a peculiar characteristic of v-PED characterized by small lacy folds of
the retinal pigment epithelium, appearing as a wrinkled PED (w-PED) on spectral
domain optical coherence tomography (SD-OCT). Our purpose was to describe the
visual prognosis and number of intravitreal injections in w-PED compared with non
w-PED. METHODS: In this retrospective, case-control series, we reviewed
retrospectively medical records of 52 eyes of 51 patients who were consecutively
included between November 1 and 30, 2015 with a previous minimum 3-year follow
up. Inclusion criteria were: neovascular age-related macular degeneration,
affected with w-PED. Baseline characteristics, best-corrected visual acuity
(BVCA), number of intravitreal anti-vascular endothelial growth factor injections
(anti-VEGF IVT) and maximal recurrence-free interval, that is, without
intravitreal anti-vascular endothelial growth factor injection, were analyzed. A
w-PED was defined as a v-PED >=200 MUm in height on SD-OCT imaging, presenting
with at least 4 small lacy folds on the surface of the retinal pigment
epithelium. Patients were compared with a control group, that is, patients
harboring PED without wrinkle shape (non-w-PED). All patients had been treated by
intravitreal anti-vascular endothelial growth factor injection of either
ranibizumab (IVR) or aflibercept (IVA) using a pro re nata (PRN) protocol after
three initial monthly treatments, with a minimum of follow-up of 3 years.
RESULTS: Two groups of patients were compared, w-PED (29 eyes, from 29 patients),
and non-w-PED (23 eyes from 22 patients). In the w-PED group, mean BCVA evolved
from 0.28 (+/-0.18) log MAR (20/40, range 20/25-20/63) at baseline, to 0.29 (+/
0.21) log MAR (20/40, range 20/25-20/63) at 1 year (P = 0.41), 0.34 (+/-0.26) log
MAR (20/40, range 20/25-20/80) at 2 years (P = 0.49), 0.35 (+/-0.28) log MAR
(20/40, range 20/25-20/80) at 3 years (P = 0.54). In the non-w-PED group, mean
BCVA was 0.40 (+/-0.28) log MAR (20/50, range 20/25-20/100) at baseline and
decreased to 0.48 (+/-0.46) log MAR (20/63, range 20/20-20/160) at 1 year (P =
0.19), 0.48 (+/-0.35) log MAR (20/63, range 20/25-20/125) at 2 years (P = 0.02),
0.60 (+/-0.38) log MAR (20/80, range 20/32-20/200) at 3 years (P = 0.002). In the
w-PED group, the mean maximal documented recurrence-free interval was 7.87 (+/
2.94) months at Year 1, 13.5 (+/-7.52) at Year 2 and 14.78 (+/-10.70) at Year 3,
versus 4.59 (+/-2.95) months at Year 1, 7.83 (+/-6.62) at Year 2, 8.57 (+/-11.18)
at Year 3 in the non-w-PED group (P = 0.0004; 0.0101; 0.0168 respectively at
Years 1, 2 and 3). DISCUSSION: The evolution of v-PED after intravitreal anti
vascular endothelial growth factor injection is still difficult to predict
despite intense clinical research in this topic. In our study, we noticed that w
PED might be a phenotypic prognosis factor for better visual acuity and longer
maximal recurrence-free interval.
PMID- 28520640
TI - TWENTY-FOUR MONTH FOLLOW-UP OF TOCILIZUMAB THERAPY FOR REFRACTORY UVEITIS-RELATED
MACULAR EDEMA.
AB - BACKGROUND: To report the 24-month efficacy and safety of the interleukin-6
receptor antagonist tocilizumab (TCZ) for refractory uveitis-related macular
edema (ME). METHODS: Data were obtained by standardized chart review. Patients
with quiescent uveitis seen at a single tertiary referral center, for whom ME was
the principal cause of reduced visual acuity. OUTCOME MEASURES: Central foveal
thickness measured by optical coherence tomography; degree of anterior and
posterior chamber; inflammation (Standardization of Uveitis Nomenclature Working
Group criteria); and visual acuity (Snellen and logarithm of the minimum angle of
resolution) were recorded in all patients during TCZ therapy at months 1, 3, 6,
12, 18, and 24. RESULTS: Sixteen eyes from 12 patients (10 women) were included.
Mean age was 34.6 years. Mean duration of ME was 13.2 years. All patients
achieved 24 months of follow-up and that is the census date for data collection.
Before TCZ was commenced, ME was present, and all patients had been previously
treated with immunosuppressive therapy and biologic agents. Uveitis diagnoses
were juvenile idiopathic arthritis associated, uveitis (n = 6), birdshot
chorioretinopathy (n = 2), idiopathic panuveitis (n = 2), sympathetic ophthalmia
(n = 1), and ankylosing spondylitis (n = 1). Mean central foveal thickness (95%;
confidence interval) was 516 +/- 55 MUm at baseline, improving to 274 +/- 13 at
Month 12 (P = 0.0004), and sustained at 274 +/- 14 at Month 24 of follow-up (P =
0.00039). Mean logarithm of the minimum angle of resolution best-corrected visual
acuity improved from 0.78 +/- 0.18 (Snellen 20/120 +/- 20/30) at baseline to 0.42
+/- 0.17 (20/52 +/- 20/30) at Month 12 (P = 0.0001) and 0.40 +/- 0.17 (20/50 +/-
20/30) at Month 24 of follow-up (P = 0.0002). Tocilizumab therapy was withdrawn
in 5 patients with sustained remission at Month 12 but in all, ME relapsed
between 1 and 3 months after TCZ discontinuation. Rechallenge of TCZ infusions
led to recovery of uveitis control and ME resolution. Two adverse events were
reported during two 4-month follow-ups: one Grade 1 neutropenia and one community
acquired pneumonia. CONCLUSION: In this long-term study, TCZ was effective and
had a comparable safety profile to published data for TCZ use in other
indications, when used for the treatment of refractory uveitis-related ME.
PMID- 28520641
TI - FIVE-YEAR FOLLOW-UP AFTER EPIRETINAL MEMBRANE SURGERY: A Single-Center
Experience.
AB - PURPOSE: To evaluate the rate of epiretinal membrane (ERM) recurrence in eyes
that underwent ERM peeling surgery at least 5 years earlier. METHODS:
Retrospective interventional case series study of 37 patients (15 women and 22
men; mean age, 70 +/- 7.6 years) operated on for ERM removal with a follow-up of
at least 5 years. The patients underwent testing for visual acuity, an ophthalmic
examination, and optical coherence tomography imaging, all of which were assessed
preoperatively, postoperatively, and at the 5-year follow-up. RESULTS: Visual
acuity significantly improved at 1 year after peeling compared with baseline (P =
0.045), and the improved results were maintained at 5 years (P = 0.804) 0.766
logarithm of the minimum angle of resolution (Snellen 6/35). The central macular
thickness decreased significantly at the 1-year follow-up compared with baseline
and continued to decrease as measured at the 5-year follow-up (P = 0.04). At 5
years, the ERM recurrence rate reached 58% (28% extrafoveal). Photoreceptor
atrophy and retinal pigment epithelium changes correlated with diabetes mellitus
(P = 0.028). CONCLUSION: The recurrence rate of ERM after peeling surgery was
reported as being around 5% to 12%. It was 58% in the current study. Because the
recurrent ERM is generally mild, visual acuity was unaffected.
PMID- 28520642
TI - INFLAMMATORY CHOROIDAL NEOVASCULAR MEMBRANE: Long-Term Visual and Anatomical
Outcomes After Intravitreal Anti-vascular Endothelial Growth Factor Therapy.
AB - PURPOSE: To assess the long-term visual and anatomical outcomes after
intravitreal anti-vascular endothelial growth factor therapy for inflammatory
choroidal neovascular membrane (CNVM). METHODS: Retrospective case series of 15
consecutive cases of newly diagnosed inflammatory CNVM who were treated with
intravitreal bevacizumab or ranibizumab injections. RESULTS: The study included 8
women and 7 men with mean age at presentation with CNVM of 40.53 +/- 17.46 years
(range, 11-70 years), and mean follow-up duration after anti-vascular endothelial
growth factor therapy was 20.53 +/- 14.53 months (range, 6-48 months). All eyes
had classic CNVM confirmed by fluorescein angiography, most commonly located in
the peripapillary area (8 eyes, 53.3%), followed by juxtafoveal (4 eyes, 26.7%),
and subfoveal location (3 eyes, 20%). All CNVMs showed complete resolution with
mean 2.6 +/- 1.2 injections per eye. Preinjection mean best-corrected visual
acuity of logarithm of minimum angle of resolution 0.79 +/- 0.76 (approximate
Snellen equivalent 20/123) and mean central macular thickness of 435.9 +/- 190.2
MUm improved significantly to mean best-corrected visual acuity of logarithm of
minimum angle of resolution 0.46 +/- 0.43 (approximate Snellen equivalent 20/58)
and mean central macular thickness of 262.13 +/- 108.70 MUm (P value 0.02 and
<0.0001, respectively) at the final visit. Recurrence was seen in 26.7% eyes
(4/15), all of which regressed with single injection. Only complication noted was
subretinal fibrosis in one eye (6.7%). CONCLUSION: For inflammatory CNVM, in
addition to immunosuppression in cases with active inflammation, anti-vascular
endothelial growth factor therapy seems as a very effective treatment modality
resulting in significant visual improvement and foveal flattening. Incidence of
major complications is rare, and the recurrence rate seems low.
PMID- 28520643
TI - Risk of Lung Cancer Mortality in Nuclear Workers from Internal Exposure to Alpha
Particle-emitting Radionuclides.
AB - BACKGROUND: Carcinogenic risks of internal exposures to alpha-emitters (except
radon) are poorly understood. Since exposure to alpha particles-particularly
through inhalation-occurs in a range of settings, understanding consequent risks
is a public health priority. We aimed to quantify dose-response relationships
between lung dose from alpha-emitters and lung cancer in nuclear workers.
METHODS: We conducted a case-control study, nested within Belgian, French, and UK
cohorts of uranium and plutonium workers. Cases were workers who died from lung
cancer; one to three controls were matched to each. Lung doses from alpha
emitters were assessed using bioassay data. We estimated excess odds ratio (OR)
of lung cancer per gray (Gy) of lung dose. RESULTS: The study comprised 553 cases
and 1,333 controls. Median positive total alpha lung dose was 2.42 mGy (mean:
8.13 mGy; maximum: 316 mGy); for plutonium the median was 1.27 mGy and for
uranium 2.17 mGy. Excess OR/Gy (90% confidence interval)-adjusted for external
radiation, socioeconomic status, and smoking-was 11 (2.6, 24) for total alpha
dose, 50 (17, 106) for plutonium, and 5.3 (-1.9, 18) for uranium. CONCLUSIONS: We
found strong evidence for associations between low doses from alpha-emitters and
lung cancer risk. The excess OR/Gy was greater for plutonium than uranium, though
confidence intervals overlap. Risk estimates were similar to those estimated
previously in plutonium workers, and in uranium miners exposed to radon and its
progeny. Expressed as risk/equivalent dose in sieverts (Sv), our estimates are
somewhat larger than but consistent with those for atomic bomb survivors.See
video abstract at, http://links.lww.com/EDE/B232.
PMID- 28520644
TI - Trade-offs of Personal Versus More Proxy Exposure Measures in Environmental
Epidemiology.
AB - The technological ability to make personal measurements of toxicant exposures is
growing rapidly. While this can decrease measurement error and therefore help
reduce attenuation of effect estimates, we argue that as measures of exposure or
dose become more personal, threats to validity of study findings can increase in
ways that more proxy measures may avoid. We use directed acyclic graphs (DAGs) to
describe conditions where confounding is introduced by use of more personal
measures of exposure and avoided via more proxy measures of personal exposure or
target tissue dose. As exposure or dose estimates are more removed from the
individual, they become less susceptible to biases from confounding by personal
factors that can often be hard to control, such as personal behaviors. Similarly,
more proxy exposure estimates are less susceptible to reverse causation. We
provide examples from the literature where adjustment for personal factors in
analyses that use more proxy exposure estimates have little effect on study
results. In conclusion, increased personalized exposure assessment has important
advantages for measurement accuracy, but it can increase the possibility of
biases from personal factors and reverse causation compared with more proxy
exposure estimates. Understanding the relation between more and less proxy
exposures, and variables that could introduce confounding are critical components
to study design.
PMID- 28520645
TI - Oxidative Stress and Breast Cancer Risk in Premenopausal Women.
AB - BACKGROUND: Detrimental effects of oxidative stress are widely recognized, but
induction of apoptosis and senescence may also have benefits for cancer
prevention. Recent studies suggest oxidative stress may be associated with lower
breast cancer risk before menopause. METHODS: We conducted a nested case-control
study (N = 457 cases, 910 controls) within the NIEHS Sister Study cohort of
50,884 women. Premenopausal women ages 35-54 were eligible for selection. We
matched controls 2:1 to cases on age and enrollment year and were breast cancer
free at the time of the corresponding case's diagnosis. Oxidative stress was
measured by urinary F2-isoprostane and metabolite (15-F2t-isoprostane-M)
concentrations. Odds ratios (OR) and 95% confidence intervals (CIs) were
calculated with multivariable conditional logistic regression. RESULTS: After
multivariable adjustment for body mass index (BMI) and other potential
confounders, the OR for breast cancer comparing the >90th (>=2.94 ng/mgCr) to
<25th percentile (1.01 ng/mgCr) was 1.1 (CI: 0.65, 1.7) for F2-isoprostane and
0.70 (CI: 0.43, 1.1) for the metabolite. Higher metabolite concentrations were
associated with lower breast cancer risk among women who were also premenopausal
(353 cases, OR: 0.59, CI: 0.34, 1.0) or <46 years (82 cases, OR: 0.15, CI: 0.06,
0.42) at diagnosis. ORs for the metabolite and breast cancer were inverse among
women with BMI 18.5-24.9 kg/m (OR: 0.47, CI: 0.18, 1.2, 208 cases) and >30 kg/m
(OR: 0.71, CI: 0.30, 1.7, 107 cases), but not among women with BMI 25-29.9 kg/m
(OR: 0.98, CI: 0.39, 2.5, 138 cases). CONCLUSIONS: Together with other studies,
our results support a possible inverse association between oxidative stress and
premenopausal breast cancer risk.
PMID- 28520646
TI - Relationship between pubertal timing and chronic nonspecific pain in adolescent
girls: the Young-HUNT3 study (2006-2008).
AB - The aim of this study was to examine a possible relationship between early
puberty and chronic nonspecific pain in 13- to 18-year-old girls. All adolescents
in Nord-Trondelag County, Norway, were invited to participate in the Young-HUNT3
study (2006-2008). Of the invited girls, 81% answered the questionnaire and of
these 3982 were 13 to 18 years of age. Menarche and perceived physical maturation
were used as exposure measures. Early menarche was defined as <12 years, normal
menarche as >=12 and <14 years, and late menarche as >=14 years. Perceived
physical maturation was divided into maturing earlier, the same or later than
others of their own age. The main outcome measure was chronic nonspecific pain,
defined as pain in at least one location not related to any known disease or
injury, for at least once a week during the last 3 months. The median age at
menarche was 13.2 years. Chronic nonspecific pain was more prevalent among girls
with early menarche (68%, 95% CI: 64%-72%) compared to girls with either normal
(55%, 95% CI: 53%-57%), late (50%, 95% CI: 46%-54%), or no menarche (35%, 95% CI:
29%-40%). The association persisted after adjusting for age, body mass index,
socioeconomic factors, and anxiety and depression. A similar association was
found between girls that perceived themselves as earlier physically matured than
their peers and chronic nonspecific pain. Headache/migraine was the most common
type of chronic nonspecific pain regardless of menarcheal age. In all reported
locations, pain was more prevalent in the group with early menarche compared to
normal or late menarche.
PMID- 28520647
TI - Altered brain structure and function associated with sensory and affective
components of classic trigeminal neuralgia.
AB - Classic trigeminal neuralgia (CTN) is a chronic neuropathic pain state
characterized by intense, piercing spasms of the orofacial region, and may be
attributable to abnormal pain processing in the central nervous system. Our study
investigated neuronal alterations using voxel-based morphometry (VBM), diffuse
tensor imaging (DTI), and resting-state functional connectivity in 38 patients
with CTN and 38 matched healthy controls. For voxel-based morphometry analyses,
patients with CTN displayed gray matter volume (GMV) reductions in the anterior
cingulate cortex (ACC) and mid-cingulate cortex, insula, secondary somatosensory
cortex (S2), primary motor cortex (M1), premotor area, and several regions in the
temporal lobe. For DTI analysis, patients compared with controls had increased
mean diffusivity (MD) and decreased fractional anisotropy (FA) in the corpus
callosum and the bilateral corona radiata, and increased mean diffusivity with no
fractional anisotropy changes across the bilateral superior longitudinal
fasciculus, the internal and external capsule, the thalamus and brainstem.
Additionally, patients with CTN had enhanced functional connectivity between the
right insula/S2 and ACC, medial prefrontal cortex, posterior cingulate cortex,
and bilateral dorsolateral prefrontal cortex. Furthermore, gray matter volume of
left inferior temporal gyrus negatively correlated with current pain intensity
and disease duration in patients, and connectivity of the right insula/S2-ACC was
negatively correlated with pain intensity, depression, and anxiety ratings. This
study provides multiple lines of evidence supporting aberrant structural and
functional patterns that are observed in patients with CTN, which may help us
better understand the pathophysiology of CTN and facilitate the development of
new therapies for this disease.
PMID- 28520648
TI - A longitudinal study of the influence of comorbidities and lifestyle factors on
low back pain in older men.
AB - Older adults are largely under-represented in low back pain (LBP) research. In
light of the ageing population, it is crucial to understand the influence of
comorbidities and lifestyle factors on the risk and prognosis of LBP in older
adults. The aims of this study were to describe the course of LBP in older men;
to investigate whether comorbidities/lifestyle factors can predict the course of
LBP in older men; to assess if comorbidities/lifestyle factors increase the risk
of developing LBP in older men. The study sample comprised 1685 older men living
in suburban Sydney, Australia. Low back pain, sociodemographic measures,
lifestyle factors, and comorbidities were assessed. Of the 1012 men with LBP at
baseline, 58% still reported having pain at the 24-month follow-up. Of those
without pain at baseline (n = 673), 28% reported pain at follow-up. The odds of
persistent pain at 24 months increased with each additional alcoholic drink/wk
(odds ratio [OR] = 1.10, 95% confidence interval [CI]: 1.01-1.22; P = 0.03) and
each additional unit of body mass index (OR = 1.28, 95% CI: 1.04-1.60; P = 0.02),
but reduced for men who speak English at home (OR = 0.58, 95% CI: 0.35-0.96; P =
0.03). In older men, free of LBP at baseline (n = 673), for every additional
comorbidity there was an increased risk of developing LBP (OR = 1.17, 95% CI:
1.00-1.37; P = 0.05). These results demonstrate the influence of lifestyle
factors and comorbidities on LBP in older men and suggest that the consideration
of these issues in management may improve outcomes.
PMID- 28520649
TI - The Effectiveness and Feasibility of Endoscopic Ultrasound-guided Transgastric
Drainage of Postoperative Fluid Collections Early After Pancreatic Surgery.
AB - PURPOSES: To assess the feasibility and usefulness of endoscopic ultrasound
guided transgastric drainage (EUS-GD) in patients who required early
postoperative drainage of peripancreatic fluid collection or postoperative
pancreatic fistulas after pancreatic surgery. PATIENTS AND METHODS: Between May
2012 and January 2016, 33 patients who developed peripancreatic fluid collection
or postoperative pancreatic fistulas after pancreatic resection underwent EUS-GD
or percutaneous drainage (PTD). Outcomes were compared retrospectively. RESULTS:
The drainage procedures were performed on postoperative day 4 to 71 (median, 12)
in the EUS-GD group, and 7 to 35 (median, 14) in the PTD group. Technical and
clinical success rates reached 92% (11/12) in the EUS-GD group, and 100% (21/21)
in the PTD group with no complications or mortality. The duration of hospital
stay after drainage was 10 to 44 (median, 15) days for EUS-GD, compared with 10
to 39 (median, 21) days for PTD. CONCLUSIONS: EUS-GD is a safe and useful method
for early drainage, which could be a good alternative to PTD.
PMID- 28520650
TI - Balloon Dilatation of the Minor Duodenal Papilla Up to 4 mm is Safe in a Porcine
Model.
AB - OBJECTIVES: Balloon dilatation of the minor duodenal papilla is a treatment
option for symptomatic pancreas divisum. The histologic effects of balloon
dilatation have not yet been evaluated. The aim of this study is to investigate
the tolerated extent of dilatation of the minor papilla. MATERIALS AND METHODS: A
dilatation of the minor papilla was performed in freshly explanted pancreas of
pigs using biliary balloon dilatators. Three organs were not dilated (control
group), in each 8 organs a dilatation of 4, 6, and 8 mm, respectively, was
performed. Tissue damage was assessed by microscopic evaluation. Ductal wall
disruption and perforation as well as a semiquantitative inflammation score was
described and compared. RESULTS: Ductal wall disruption was increased by
dilatation of 6 (5/8; P=0.019) and 8 mm (6/8; P=0.006) compared with 4 mm (1/8).
Median inflammation score was 0 (0 to 0), 1 (0 to 2), and 1 (0 to 2) for
dilatation of 4, 6, and 8 mm, respectively (4 vs. 6 mm, P=0.007; 4 vs. 8 mm,
P=0.026). No perforation occurred in the 4 (0/8) and 6 mm (0/8) group, 1
perforation occurred in the 8 mm group (1/8). CONCLUSIONS: A dilatation of up to
4 mm seems to be safe. However, dilatation of the minor papilla from 4 mm onwards
is increasingly associated with tissue damage. These findings should be
considered in endoscopic procedures dilating the minor duodenal papilla.
PMID- 28520651
TI - Laparoscopic Management of Hepatocellular Carcinoma: A Critical Reappraisal.
AB - Following the introduction of the first laparoscopic liver resection, after ~25
years, a critical reappraisal seems to be warranted. Liver resection represents
the first choice for curing early hepatocellular carcinoma (HCC) allowing a
curative chance also in selected patients with intermediate stage tumors. The
criteria for liver resectability by laparoscopy remains the same for open
surgery, which is oncological criteria (absence of extrahepatic tumor location;
completely resectable R0 resection), anatomic (resectability of involved segment
with its own blood surely and biliary drainage; absence of vascular invasion of
portal or hepatic veins) and technical (possibility to leave in place a residual
volume >=40%). Anatomic resections being more challenging than wedged resections,
were initially performed mainly for lesions located in the left liver (segments
2, 3, and 4) and segments 5 and 6 of the right liver (anterior and lateral
hepatic segments). Left lateral segmentectomy seemed most suited for laparoscopic
resection because of the thinness of the liver, the possibility of resection
without hilar dissection, ease of stapling the left hepatic vein and portal
pedicles of segment II and III by mechanical stapling. Conversely, right
hepatectomy seemed most difficult and technically challenging to perform. The
analysis of literature confirms that minor liver resections for HCC can be safely
conducted also in cirrhotic patients and that laparoscopy, when feasible, should
be the approach of first choice. As mentioned, there have been several studies
that compared the long-term outcomes of laparoscopic hepatectomy (LH) versus open
hepatectomy for HCC, even in cirrhotic patients, showing that laparoscopy does
not seem to have any impact on the risk of postoperative HCC recurrence. However,
further studies seem to be required, especially for long-term oncological results
and for major hepatectomy, before LH become a common alternative to open liver
surgery. The practice of performing LH (major) is challenging, due to the
significant complexity of these interventions.
PMID- 28520652
TI - A Systematic Review and Meta-Analysis of Laparoscopic and Open Distal
Pancreatectomy of Nonductal Adenocarcinomatous Pancreatic Tumor (NDACPT) in the
Pancreatic Body and Tail.
AB - BACKGROUND: Currently, laparoscopic distal pancreatectomy is regarded as a safe
and effective surgical approach for lesions in the body and tail of the pancreas.
This review examined the evidence from published data of comparative studies of
laparoscopic versus open distal pancreatectomy of nonductal adenocarcinomatous
pancreatic tumor in pancreatic body and tail. METHODS: A systematic review of the
studies comparing laparoscopic and open distal pancreatectomy was conducted.
Comparative studies published between January 1996 and June 2016 were included.
Studies were selected on the basis of specific inclusion and exclusion criteria.
These 2 techniques were compared regarding several outcomes of interest, which
were divided into preoperative, operative, postoperative, and pathologic
characteristics, postoperative biomarker, and hospital stay cost. Sensitivity and
subgroup analysis partially confirmed the robustness of these data. RESULTS: Ten
comparative case-control studies involving 712 patients (53.7% laparoscopic and
46.3% open), who underwent a distal pancreatectomy were included. The results
favored laparoscopy with regard to intraoperative blood loss (P=0.0001), the rate
of blood transfusion (P=0.02), total hospital stay (P=0.004), postoperative
hospital stay (P<0.0001), overall morbidity (P=0.0002), the rate of wound
infection (P=0.05), time to initial feeds (P<0.0001), first flatus time
(P=0.008), duration of pain-killer intake (P=0.0003), and C-reactive protein on
postoperative day 1 (P=<0.0001). In the subgroup analysis, excluding western
country studies, operation time changed to have a statistically significant
difference between these 2 groups (P=0.02). CONCLUSIONS: Laparoscopic resection
results in improved operative and postoperative outcomes compared with open
surgery according to the results of the present meta-analysis. It may be a safe
and feasible option for nonductal adenocarcinomatous pancreatic tumor patients in
pancreatic body and tail. However, randomized controlled trials should be
undertaken to confirm the relevance of these findings.
PMID- 28520653
TI - Transenteric ERCP for Treatment of Choledocholithiasis After Duodenal Switch.
AB - This article aims to describe step-by-step technique performed with the aid of a
video. We report the performance of an endoscopic approach to the biliary tract
on 2 patients who had previously undergone duodenal switch (DS). It was
successfully performed a laparoscopic-assisted transenteric endoscopic retrograde
cholangiopancreatography (ERCP) in both the patients. Although successful
experiences with ERCP after Roux-en-Y gastric bypass have been found, few cases
of ERCP after DS have been reported. Nevertheless, this is the first study to
include a multimedia video with description of details and all technical steps of
the transenteric ERCP performed on 2 patients who had previously undergone DS.
Transenteric access is a feasible technique for reaching the biliary tract
through endoscopy after DS. This technique could avoid most invasive and risky
procedures. However, it requires a high level of therapeutic endoscopic training.
PMID- 28520655
TI - Effectiveness of Intracavitary Electrocardiogram Guidance in Peripherally
Inserted Central Catheter Tip Placement in Neonates.
AB - Correct tip location is crucial for a peripherally inserted central catheter
(PICC) to maximize the effects of central venous infusion. However, it is
difficult to place the tip in a correct location in neonates because of the
unreliable estimated length by surface landmark. Therefore, we evaluated the
feasibility and safety of an improved intracavitary electrocardiogram (IC-ECG)
technique in guiding PICC placement in neonates based on the ratios of P/R wave
amplitudes on IC-ECG. The results showed that all of the 32 neonates whose PICCs
had been successfully placed and correct tip position verified by chest
radiography acquired qualified P wave on IC-ECG. The average ratio of P/R wave
amplitude was 0.6 +/- 0.1, with a range of 0.4 to 0.8. The 49 neonates who
received IC-ECG-guided PICC catheterization showed higher success rates of
correct PICC tip position on the first attempt than traditional, predetermined
length estimation on surface landmark (93.9% vs 62.5%, chi = 18.01, P < .001). No
significant complications occurred in the studied neonates. Based on these
findings, IC-ECG-guided tip placement appears to be a promising approach in
improving the success rate of tip location when placing a PICC in neonates.
PMID- 28520654
TI - Systematic Review of Hydrotherapy Research: Does a Warm Bath in Labor Promote
Normal Physiologic Childbirth?
AB - Health sciences research was systematically reviewed to assess randomized
controlled trials of standard care versus immersion hydrotherapy in labor before
conventional childbirth. Seven studies of 2615 women were included. Six trials
examined hydrotherapy in midwifery care and found an effect of pain relief; of
these, 2 examined analgesia and found reduced use among women who bathed in
labor. One study each found that hydrotherapy reduced maternal anxiety and fetal
malpresentation, increased maternal satisfaction with movement and privacy, and
resulted in cervical dilation progress equivalent to standard labor augmentation
practices. Studies examined more than 30 fetal and neonatal outcomes, and no
benefit or harm of hydrotherapy was identified. Two trials had anomalous findings
of increased newborn resuscitation or nursery admission after hydrotherapy, which
were not supported by additional results in the same or other studies. Review
findings demonstrate that intrapartum immersion hydrotherapy is a helpful and
benign practice. Hydrotherapy facilitates physiologic childbirth and may increase
satisfaction with care. Maternity care providers are recommended to include
hydrotherapy among routine labor pain management options and consider immersion
to promote progress of normal or protracted labor, particularly among women with
preferences to avoid obstetric medications and procedures.
PMID- 28520656
TI - The Power of a Parent's Touch: Evaluation of Reach and Impact of a Targeted
Evidence-Based YouTube Video.
AB - Despite strong evidence that skin-to-skin contact and breast-feeding are
effective pain-relieving interventions for infants undergoing painful procedures,
they remain underutilized in clinical practice. Given the important contribution
of parents, there is a need to find innovative ways to assist parents to become
actively involved in their infant's care. We developed a YouTube video to
disseminate evidence-based information on the effectiveness of skin-to-skin
contact and breast-feeding for infant pain management. The 2-minute 39-second
video launched on December 2, 2014, and was promoted through Web-based and in
person communication and YouTube advertisements. Data were collected using
YouTube analytics and an online survey. Post-18 months from its launch, the video
had a reach of 157 938 views from 154 countries, with most viewers watching an
average of 73% of the video (1 minute 56 seconds). Parents (n = 32) and
healthcare providers (n = 170) completed the survey. Overall, both reported that
they liked the video, found it helpful, felt more confident, and were more likely
to use skin-to-skin contact (16% and 12%) and breast-feeding (3% and 11%),
respectively, during future painful procedures. Despite the high-viewing
patterns, alternative methods should be considered to better evaluate the impact
on practice change.
PMID- 28520657
TI - CT-based Techniques for Brain Perfusion.
AB - Recent rapid advances in endovascular treatment for acute ischemic stroke
highlight the crucial role of neuroimaging especially multimodal computed
tomography (CT) including CT perfusion in stroke triage and management decisions.
With an increasing focus on changes in cerebral physiology along with time-based
matrices in clinical decisions for acute ischemic stroke, CT perfusion provides a
rapid and practical modality for assessment and identification of salvageable
tissue at risk and infarct core and provides a better understanding of the
changes in cerebral physiology. Although there are challenges with the lack of
standardization and accuracy of quantitative assessment, CT perfusion is evolving
as a cornerstone for imaging-based strategies in the rapid management of acute
ischemic stroke.
PMID- 28520659
TI - Predictors of Satisfaction With Life in Veterans After Traumatic Brain Injury: A
VA TBI Model Systems Study.
AB - OBJECTIVE: To identify predictors of satisfaction with life in Veterans 1 year
after traumatic brain injury (TBI). SETTING: The VA TBI Model Systems (TBIMS)
project includes 5 Veterans Affairs (VA) Polytrauma Rehabilitation Centers.
PARTICIPANTS: Veterans enrolled in the VA TBIMS study who completed the
Satisfaction With Life Scale at year 1 follow-up. The sample is largely male
(96%) and Caucasian (72%), with a median age of 27 years upon enrollment. DESIGN:
Prospective observational cohort study measuring including demographics (eg,
education), preinjury variables (eg, mental health history and employment), and
military variables (eg, injury during deployment and injury during active duty
status). MAIN OUTCOME MEASURE: Satisfaction With Life Scale. RESULTS:
Multivariate regression analyses revealed that age, marital status, preinjury
employment status, preinjury mental health history, and active duty status at the
time of injury were significant predictors of life satisfaction at year 1 follow
up. CONCLUSIONS: Results of this study suggest that satisfaction with life in
Veterans with TBI is mediated by several factors that might inform rehabilitation
interventions and discharge recommendations. Preinjury variables and active duty
status (a unique aspect of the Veteran population) influence life satisfaction at
1 year postinjury. Limitations and future clinical implications will be
discussed.
PMID- 28520658
TI - Age-Group and Gender Differences in Stroke Knowledge in an Israeli Jewish Adult
Population.
AB - BACKGROUND: Stroke is a leading cause of long-term disability and the fifth
leading cause of death in Israel. Knowledge of stroke warning signs has been
linked to early seeking of medical help. Little is known about knowledge of
stroke warning signs in Israeli Jewish adults. METHODS: Stroke knowledge was
examined among Jewish Israeli adults. Using a structured questionnaire,
registered nurses interviewed a convenience sample of the respondents, 18 years
or older, with no stroke history. Stroke knowledge and demographics were examined
by 3 age groups (<45, 45-64, and >64 years) in men and women. RESULTS: In total,
1137 Jewish Israelis were interviewed, 457 (40.2%) men and 680 women (59.8%); 493
(43.4%) were younger than 45 years, 541 (47.6%) were aged 45 to 64 years, and 102
(9%) were older than 64 years; 1 (0.1%) did not report age. On average, each
interview lasted for 25 to 30 minutes. Participants younger than 45 years showed
the lowest knowledge of stroke cause. Women younger than 45 years were less
likely to identify at least 2 stroke warning signs. Participants younger than 45
years were less likely to identify at least 2 risk factors, compared with
participants aged 45 to 64 years and older than 64 years. Women younger than 45
years were less likely to identify at least 2 stroke prevention strategies.
CONCLUSION: Participants younger than 45 years showed the lowest levels of stroke
knowledge. The highest stroke knowledge was found in the 45 to 64 years age
group. Stroke knowledge among different age groups was similar in both genders.
Educational campaigns aimed at increasing knowledge of stroke among the general
population and targeting the younger population are recommended.
PMID- 28520660
TI - Childhood Trauma and Lifetime Traumatic Brain Injury Among Individuals Who Are
Homeless.
AB - OBJECTIVES: To study the association of childhood trauma and lifetime prevalence
of traumatic brain injury (TBI) among individuals who are homeless. DESIGN: Cross
sectional survey. SETTING: Three cities in British Columbia, Canada.
PARTICIPANTS: Five hundred individuals who are homeless and 19 years of age or
older in 2009. MEASUREMENTS: Traumatic brain injury was identified with National
Survey of Homeless Assistance Providers and Clients (NSHAPC) and childhood trauma
using the Childhood Trauma Questionnaire-Short Form (CTQ-SF). The relationship
between childhood trauma and TBI was explored using multivariable logistic
regression approach, adjusting for age, gender, any psychiatric diagnosis
(anxiety disorder, mood disorder, psychosis), alcohol dependence, and substance
dependence. The effect of number of childhood trauma types on TBI was also
explored using multiple variables logistic regression approach adjusting for the
same covariates. RESULTS: The prevalence of TBI was 63.6% and childhood
maltreatment was 87.7% among the sample population. During childhood of 487
participants included in the analysis, 57.7% experienced physical abuse, 62.8%
physical neglect, 45.8% sexual abuse, 62.4% emotional abuse, and 55.2% emotional
neglect. After adjustment, childhood trauma (adjusted odds ratio [aOR] = 2.26;
95% confidence interval [CI], 1.04-5.02), childhood physical abuse (aOR = 2.13;
95% CI, 1.19-3.87; n = 487), and childhood emotional abuse (aOR = 1.95; 95% CI,
1.09-3.51; n = 487) were significantly associated with history of TBI. After
adjustment, having 4 different types of childhood trauma (aOR = 2.81; 95% CI,
1.11-7.31) was significantly associated with higher odds of reporting TBI
history. CONCLUSIONS: Childhood trauma is significantly associated with lifetime
prevalence of TBI in homeless populations in British Columbia, Canada, indicating
an added level of vulnerability in this population. In addition, these findings
suggest a potential role for childhood trauma prevention strategies and services
mindful of the patients' history of trauma for this particularly vulnerable
population.
PMID- 28520661
TI - Traumatic Brain Injury and Depression in a Community-Based Sample: A Cohort Study
Across the Adult Life Span.
AB - OBJECTIVES: To determine whether self-reported traumatic brain injuries (TBIs)
are associated with "cases" of clinically significant depression in the general
community. To examine interactions between variables previously linked to
depression after a TBI. SETTING: Population-based community study (Canberra and
Queanbeyan, Australia). PARTICIPANTS AND DESIGN: Three age cohorts: young, middle
aged, and older adults (aged 20-24, 40-44, and 60-64 years at baseline) randomly
selected from the electoral roll and followed across 3 waves (4 years apart). A
total of 7397, 6621, and 6042 people provided their TBI history in waves 1 to 3.
MEASURES: Lifetime (TBIlifetime: sustained at any time since birth), recent
(TBIrecent: in the preceding 4 years), and multiple (TBImultiple: more than 1)
TBIs, current depression, and known risk factors for depression (age, sex,
marital/employment status, prior history of depression, medical conditions,
recent life events, alcohol consumption, social support, physical activity).
RESULTS: Generalized estimating equations demonstrated a significant association
between sustaining a TBI and experiencing clinically significant depression
(cases), even after controlling for multiple demographic and health/lifestyle
factors. CONCLUSION: There is an enduring association between depression and TBI,
suggesting that, following a TBI, individuals should be monitored and supported
to optimize their long-term psychological health.
PMID- 28520662
TI - Anxiety Disorders in Adults With Childhood Traumatic Brain Injury: Evidence of
Difficulties More Than 10 Years Postinjury.
AB - OBJECTIVE: To explore long-term psychiatric outcomes in individuals with a
history of childhood traumatic brain injury (TBI) or orthopedic injury (OI).
SETTING: Hospital emergency department, medical admission records and outpatient
settings. PARTICIPANTS: There were 95 males (M = 22.78 years, SD = 3.44 years)
and 74 females (M = 22.27 years, SD = 3.09 years), 65 with mild TBI (M = 23.25
years, SD = 3.58 years), 61 with moderate-severe TBI (M = 22.34 years, SD = 2.79
years), and 43 with OI (M = 21.81 years, SD = 3.36 years). DESIGN: Longitudinal,
between-subjects, cross-sectional design using retrospective and current data.
MAIN MEASURES: Semistructured interview to obtain psychiatric diagnoses and
background information, and medical records for identification of TBI. RESULTS:
Group with moderate-severe TBI presented with significantly higher rates of any
anxiety disorder (chi2 = 6.81, P = .03) and comorbid anxiety disorder (chi2 =
6.12, P < .05). Group with overall TBI presented with significantly higher rates
of any anxiety disorder (chi1 = 5.36, P = .02), panic attacks (chi1 = 4.43, P =
.04), specific phobias (chi1 = 4.17, P = .04), and depression (chi1 = 3.98, P <
.05). Prediction analysis revealed a statistically significant model (chi7 =
41.84, P < .001) explaining 23% to 37% of the variance in having any anxiety
disorder, with significant predictors being group (TBI) and gender (female).
CONCLUSIONS: Children who have sustained a TBI may be vulnerable to persistent
anxiety, panic attacks, specific phobias, and depression, even 13 years after the
injury event.
PMID- 28520663
TI - Contributions to Executive Dysfunction in Operation Enduring Freedom/Operation
Iraqi Freedom Veterans With Posttraumatic Stress Disorder and History of Mild
Traumatic Brain Injury.
AB - OBJECTIVE: Posttraumatic stress disorder (PTSD), history of mild traumatic brain
injury (mTBI), and executive function (EF) difficulties are prevalent in
Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans. We
evaluated the contributions of injury variables, lower-order cognitive component
processes (processing speed/attention), and psychological symptoms to EF.
PARTICIPANTS: OEF/OIF Veterans (N = 65) with PTSD and history of mTBI were
administered neuropsychological tests of EF and self-report assessments of PTSD
and depression. RESULTS: Those impaired on one or more EF measures had higher
PTSD and depression symptoms and lower processing speed/attention performance
than those with intact performance on all EF measures. Across participants,
poorer attention/processing speed performance and higher psychological symptoms
were associated with worse performance on specific aspects of EF (eg, inhibition
and switching) even after accounting for injury variables. Although direct
relationships between EF and injury variables were equivocal, there was an
interaction between measures of injury burden and processing speed/attention such
that those with greater injury burden exhibited significant and positive
relationships between processing speed/attention and inhibition/switching,
whereas those with lower injury burden did not. CONCLUSION: Psychological
symptoms as well as lower-order component processes of EF (attention and
processing speed) contribute significantly to executive dysfunction in OEF/OIF
Veterans with PTSD and history of mTBI. However, there may be equivocal
relationships between injury variables and EF that warrant further study. Results
provide groundwork for more fully understanding cognitive symptoms in OEF/OIF
Veterans with PTSD and history of mTBI that can inform psychological and
cognitive interventions in this population.
PMID- 28520664
TI - Follow-Up Care Adherence After Hospital Discharge in Children With Traumatic
Brain Injury.
AB - OBJECTIVE: To investigate factors associated with follow-up care adherence in
children hospitalized because of traumatic brain injury (TBI). DESIGN: An urban
level 1 children's hospital trauma registry was queried to identify patients (2
18 years) hospitalized with a TBI in 2013 to 2014. Chart reviewers assessed
discharge summaries and follow-up instructions in 4 departments. MAIN MEASURES:
Three levels of adherence-nonadherence, partial adherence, and full adherence-and
their associations with care delivery, patient, and injury factors. RESULTS: In
our population, 80% were instructed to follow up within the hospital network.
These children were older and had more severe TBIs than those without follow-up
instructions and those referred to outside providers. Of the 352 eligible
patients, 19.9% were nonadherent, 27.3% were partially adherent, and 52.8% were
fully adherent. Those recommended to follow up with more than 1 department had
higher odds of partial adherence over nonadherence (adjusted odds ratio [AOR] =
5.8, 95% CI: 1.9-17.9); however, these patients were less likely to be fully
adherent (AOR = 0.1; 95% CI: 0.1-0.3). Privately insured patients had a higher
AOR of full adherence. CONCLUSIONS: Nearly 20% of children hospitalized for TBI
never returned for outpatient follow-up and 27% missed appointments. Care
providers need to educate families, coordinate service provision, and promote
long-term monitoring.
PMID- 28520665
TI - Family History of Migraine Associated With Posttraumatic Migraine Symptoms
Following Sport-Related Concussion.
AB - OBJECTIVE: To determine whether family history of migraine increased the
likelihood of posttraumatic migraine (PTM) symptom presentation in adolescents
following concussion, and examine the influence of family history of migraine and
PTM on postinjury outcomes. SETTING: Outpatient concussion clinic. PARTICIPANTS:
A total of 153 patients with concussion (103 males and 50 females) aged 15.72 +/-
1.48 years (range 12-18 years). DESIGN: Cross-sectional, observational study of
patients presenting for initial evaluation 4.72 +/- 3.05 days (range 1-14)
postinjury. MAIN MEASURES: Computerized neurocognitive testing, symptom report,
and vestibular/oculomotor screening. RESULTS: Patients with a family history of
migraine were 2.6 times (odds ratio = 2.60, confidence interval = 1.35-5.02, P =
.003) more likely to present with PTM compared with patients without a family
history. Results of multivariate analyses of covariance, controlling for
concussion history, revealed significant main effects for PTM on (1) Immediate
Post-Concussion Assessment and Cognitive Testing (ImPACT)/Post-Concussion Symptom
Scale (PCSS) (F = 15.43, P <.001) and (2) Vestibular/Ocular Motor Screening
(VOMS) (F = 8.52, P < .001). There was no main effect for family history of
migraine on ImPACT/PCSS (P = .22) and VOMS (P = .83) or interaction between
family history of migraine and PTM on ImPACT/PCSS (P = .84) and VOMS (P = .52).
CONCLUSION: Family history of migraine is associated with PTM symptoms following
sport-related concussion, suggesting a genetic predisposition for migraine may
serve as a catalyst or trigger for onset of PTM. However, only presence of PTM,
rather than family history of migraine, was related to worse neurocognitive and
vestibular/oculomotor outcomes.
PMID- 28520667
TI - Supervision Needs Following Veteran and Service Member Moderate to Severe
Traumatic Brain Injury: A VA TBI Model Systems Study.
AB - OBJECTIVE: To characterize supervision levels across residential settings at 1
year post-TBI and explore predictors of supervision in a Veteran and Service
member population. SETTING: Five VA Polytrauma Rehabilitation Centers.
PARTICIPANTS: A total of 302 individuals enrolled in the VA TBI Model Systems
(TBIMS) research program. DESIGN: Prospective, longitudinal, multisite. MAIN
MEASURES: Primary residence and supervision levels measured via scores on the
Supervision Rating Scale. For predictive modeling, scores were dichotomized into
2 groups: those that were fully independent/living alone or required only some
supervision during the day (independent group, n = 195) and those that required
overnight supervision, full-time indirect supervision, and full-time direct
supervision (dependent group, n = 107). RESULTS: Thirty-five percent were
receiving supervision at 1 year post-TBI across residential settings and 28% were
living in alternative settings. Multivariate modeling indicated that older age
and longer posttraumatic amnesia (PTA) were predictive of having a need for
supervision at 1 year postinjury. CONCLUSIONS: Supervision needs are long-term
features of moderate and severe TBI. Results of this study lend support to the
shift toward conceptualizing TBI as a chronic disease.
PMID- 28520666
TI - Anger Self-Management Training for Chronic Moderate to Severe Traumatic Brain
Injury: Results of a Randomized Controlled Trial.
AB - OBJECTIVE: To test efficacy of 8-session, 1:1 treatment, anger self-management
training (ASMT), for chronic moderate to severe traumatic brain injury (TBI).
SETTING: Three US outpatient treatment facilities. PARTICIPANTS: Ninety people
with TBI and elevated self-reported anger; 76 significant others (SOs) provided
collateral data. DESIGN: Multicenter randomized controlled trial with 2:1
randomization to ASMT or structurally equivalent comparison treatment, personal
readjustment and education (PRE). Primary outcome assessment 1 week
posttreatment; 8-week follow-up. PRIMARY OUTCOME: Response to treatment defined
as 1 or more standard deviation change in self-reported anger. SECONDARY
OUTCOMES: SO-rated anger, emotional and behavioral status, satisfaction with
life, timing of treatment response, participant and SO-rated global change, and
treatment satisfaction. MAIN MEASURES: State-Trait Anger Expression Inventory
Revised Trait Anger (TA) and Anger Expression-Out (AX-O) subscales; Brief Anger
Aggression Questionnaire (BAAQ); Likert-type ratings of treatment satisfaction,
global changes in anger and well-being. RESULTS: After treatment, ASMT response
rate (68%) exceeded that of PRE (47%) on TA but not AX-O or BAAQ; this finding
persisted at 8-week follow-up. No significant between-group differences in SO
reported response rates, emotional/behavioral status, or life satisfaction. ASMT
participants were more satisfied with treatment and rated global change in anger
as significantly better; SO ratings of global change in both anger and well-being
were superior for ASMT. CONCLUSION: ASMT was efficacious and persistent for some
aspects of problematic anger. More research is needed to determine optimal dose
and essential ingredients of behavioral treatment for anger after TBI.
PMID- 28520669
TI - Investigating the Connection Between Traumatic Brain Injury and Posttraumatic
Stress Symptoms in Adolescents.
AB - OBJECTIVE: To identify potentially modifiable individual and social-environmental
correlates of posttraumatic stress symptoms (PTSS) among adolescents hospitalized
for traumatic brain injury (TBI). SETTING: Four pediatric hospitals and 1 general
hospital in the United States. PARTICIPANTS: Children ages 11 to 18 years,
hospitalized for moderate-severe TBI within the past 18 months. DESIGN:
Retrospective cross-sectional analysis. MAIN MEASURES: The University of
California at Los Angeles (UCLA) Post-traumatic Stress Disorder (PTSD) Reaction
Index and the Youth Self-Report (YSR) PTSD subscale. RESULTS: Of 147 adolescents
enrolled, 65 (44%) had severe TBI, with an average time since injury of 5.8 +/- 4
months. Of the 104 who completed the UCLA-PTSD Reaction Index, 22 (21%) reported
PTSS and 9 (8%) met clinical criteria for PTSD. Of the 143 who completed the YSR
PTSD subscale, 23 (16%) reported PTSS and 6 (4%) met clinical criteria for PTSD.
In multivariable analyses, having a negative approach to problem solving and
depressive symptoms were both associated (P < .001) with higher levels of PTSS
based on the UCLA-PTSD Reaction Index (beta = 0.41 and beta = 0.33, respectively)
and the YSR-PTSD subscale (beta = 0.33 and beta = 0.40, respectively).
CONCLUSION: Targeting negative aspects of problem solving in youths after brain
injury may mitigate PTSS.
PMID- 28520668
TI - Structural Connectivity Related to Persistent Symptoms After Mild TBI in
Adolescents and Response to Aerobic Training: Preliminary Investigation.
AB - OBJECTIVE: To quantify structural connectivity abnormalities in adolescents with
mild traumatic brain injury (mTBI) and to investigate connectivity changes
following aerobic training using graph theory and diffusion tensor imaging
tractography. SETTING: Outpatient research setting. PARTICIPANTS: Twenty-two
children (age: 15.83 +/- 1.77 years, 10 females) with 4 to 16 weeks of persistent
symptoms after mTBI and a matched healthy comparison group. DESIGN: Randomized
clinical trial of aerobic training and stretching comparison combined with case
control comparison. MAIN MEASURES: (1) Five global network measures: global
efficiency (Eglob), mean local efficiency, modularity, normalized clustering
coefficient (gamma), normalized characteristic path length (lambda), and small
worldness (sigma). (2) The self-reported Post-Concussion Symptom Inventory score.
RESULTS: At initial enrollment, adolescents with mTBI had significantly lower
Eglob and higher gamma, lambda, and sigma (all P < .05) than healthy peers. After
the intervention, significantly increased Eglob and decreased lambda (both P <
.05) were found in the aerobic training group. Improvement in Post-Concussion
Symptom Inventory scores was significantly correlated with the Eglob increase and
lambda decrease in the aerobic training and lambda decrease in the stretching
comparison group (all P < .05). CONCLUSION: This pilot study showed initial
evidence that structural connectivity analysis was sensitive to brain network
abnormalities and may serve as an imaging biomarker in children with persistent
symptoms after mTBI.
PMID- 28520670
TI - Neutrophil to Lymphocyte Ratio as a Novel Predictor of Outcome in Patients With
Severe Traumatic Brain Injury.
AB - OBJECTIVE: The neutrophil to lymphocyte ratio (NLR) has been reported to be a
predictor of outcome in critical illness. Objective of this study was to
investigate the changes of the NLR in patients with severe traumatic brain injury
(TBI) and analyze the relationship between the NLR and TBI outcome. SETTING:
China. PARTICIPANTS: A total of 855 patients with severe TBI from January 2007 to
April 2012. DESIGN: Retrospective. MAIN MEASUREMENT: Data on the NLR and other
indicators were collected. After follow-up until death or 1 year, the
relationship between the NLR and TBI outcome was analyzed retrospectively.
RESULTS: The final analysis included 688 patients. There were 508 (73.8%) who had
an unfavorable outcome by 1 year after head trauma. The value of the NLR on
admission was significantly higher in the unfavorable outcome group than in the
favorable outcome group (P < .001). Multivariate logistic analysis showed that
higher NLR was associated with an unfavorable outcome (odds ratio, 1.100; P <
.001). Receiver operating characteristic curve analysis showed that the NLR had a
sensitivity of 60.2% and a specificity of 71.1% for predicting unfavorable
outcome at 1 year on the basis of the best threshold. CONCLUSION: The NLR might
be useful as a novel predictor for 1-year outcome and mortality in severe TBI.
PMID- 28520671
TI - Living Life After Traumatic Brain Injury: Phase 1 of a Longitudinal Qualitative
Study.
AB - OBJECTIVE: To explore what helps and hinders recovery and adaptation after
disabling traumatic brain injury (TBI) and make recommendations for improving
service responsiveness. DESIGN: A longitudinal qualitative descriptive study
across all TBI severities. SETTING: Community. PARTICIPANTS: Forty people with
TBI, and 22 significant others, 6 to 9 months following a TBI. MAIN MEASURES:
Semistructured interviews, analyzed using qualitative description, focused on (a)
key areas of importance or concern and (b) strategies or actions that people
found helpful or that hindered recovery. RESULTS: Traumatic brain injury produced
a complex set of challenges in keeping up with life, and understanding what
having a TBI means for, and to, me. This period encompassed a tangled fit and
misfit in life as brain injury did not occur in isolation. People had to actively
change some aspects of life and yet allow other changes to happen. Valued
supports from others included being looked out for and having someone to help
drive the process. CONCLUSION: Improved services delivery and better outcomes may
result if we respond to the person within his or her context; listen, believe,
and acknowledge the person's story through our actions; and avoid assumptions
about aspects of life that mean most to people and who/what may help best.
PMID- 28520673
TI - Behavioral Clinical Trials in Moderate to Severe Pediatric Traumatic Brain
Injury: Challenges, Potential Solutions, and Lessons Learned.
AB - : The purpose of this commentary is to outline the challenges encountered when
conducting clinical trials of interventions for pediatric traumatic brain injury
(TBI) and share potential solutions for surmounting these issues. This commentary
grows out of our experience implementing 8 randomized clinical trials (RCTs) of
family-centered interventions to reduce child behavior problems and
caregiver/parent distress following pediatric brain injury. These studies,
involving more than 600 participants from 8 clinical centers, support the
feasibility of conducting RCTs with children who have sustained TBIs while
highlighting potential challenges and threats to validity. The challenges of
behavioral trials for pediatric TBI are apparent but not insurmountable. Careful
consideration of the clinical trial issues outlined in this commentary can inform
design choices and analyses when planning a clinical trial. It is critically
important that investigators share their failures as well their successes to move
the field of pediatric TBI intervention research forward.
PMID- 28520672
TI - Sertraline for Major Depression During the Year Following Traumatic Brain Injury:
A Randomized Controlled Trial.
AB - OBJECTIVE: Major depressive disorder (MDD) is common and associated with impaired
functioning after traumatic brain injury (TBI). Few placebo-controlled
antidepressant trials exist in this population. We evaluated the efficacy and
tolerability of sertraline for MDD within 1 year of sustaining a TBI. SETTING:
Level I trauma center. PARTICIPANTS: Adults with MDD within 1 year of
hospitalization for complicated mild to severe TBI. DESIGN: Randomized, double
blind, placebo-controlled trial. MAIN MEASURES: Twelve-week treatment response on
the 17-item Hamilton Depression Rating Scale. We also assessed symptom
improvement and remission. RESULTS: We randomized 62 participants: 32% sustained
a severe TBI, 68% had significant anxiety, 63% had a history of prior MDD, and
69% had a history of alcohol or drug dependence. Depression significantly
improved from baseline to 12 weeks in both treatment groups (P < .001). There
were no significant differences between the sertraline and placebo groups over 12
weeks on depression severity, response, or remission. The sertraline group had
significant improvement on speed of information processing compared with the
placebo group (P < .006). CONCLUSION: Sertraline monotherapy was not superior to
placebo for MDD in people with post-acute complicated mild to severe TBI.
Research is needed on the effectiveness of interventions that also address the
significant psychosocial needs of this population.
PMID- 28520676
TI - Describing Weight Loss Attempts and Physical Activity Among Individuals With TBI
Prior to Participation in a Weight-Loss Program.
AB - OBJECTIVE: Describe (1) weight loss history, (2) perceptions about lifestyle
changes, and (3) physical activity among a sample of individuals with traumatic
brain injury prior to a 12-month lifestyle change program. SETTING: Community
based. PARTICIPANTS: Individuals enrolled in a lifestyle change program, 6 months
or more post-traumatic brain injury, body mass index of 25 or greater, 18 to 64
years of age, with physician's clearance to participate. DESIGN: Convenience
sample. MAIN MEASURES: Self-report data were collected before beginning the
lifestyle change program including descriptive, weight loss history and physical
activity behavior using the Modifiable Activity Questionnaire. RESULTS: The final
sample included 22 participants (M age = 46 years) injured a median of 8 years
ago. Mean weight was 208.5 lb (SD = 40.2), with average body mass index of 31.84
(SD = 4.4). Since injury, 72.7% reported prior weight loss attempts, with 50%
gaining 10 lb or more. All participants indicated high motivation for lifestyle
changes. Perceived benefits included feeling better, improving overall health,
and increased energy. Barriers included physical health complications. Types of
physical activity completed included walking (68%, 180 min/mo) and swimming (32%,
79 min/mo). CONCLUSION: Results indicate that many individuals gained weight
since injury and attempted weight loss, demonstrating a need for evidence-based
lifestyle interventions. Future research is needed to determine whether
individuals with traumatic brain injury are able to achieve and maintain weigh
loss through intervention.
PMID- 28520674
TI - Relationship Stability After Traumatic Brain Injury Among Veterans and Service
Members: A VA TBI Model Systems Study.
AB - OBJECTIVE: To explore stability of relationships and predictors of change in
relationship status 2 years following TBI/polytrauma. SETTING: Five Department of
Veterans Affairs Polytrauma Rehabilitation Centers (VA PRCs). PARTICIPANTS: A
total of 357 active duty service members and Veterans enrolled in the Veterans
Affairs Polytrauma Rehabilitation Centers Traumatic Brain Injury Model Systems
database with complete marital status information at 2 years postinjury. DESIGN:
Prospective, longitudinal, multisite. MAIN MEASURES: Relationship status change
was defined as change in marital status (single/never married; married;
divorced/separated) at 2-year follow-up, compared with status at enrollment.
RESULTS: At the time of enrollment, 134 participants (38%) were single/never
married; 151 (42%) were married, and 72 (20%) were divorced/separated. Of those
married at enrollment, 78% remained married at year 2 while 22% underwent
negative change. Multivariable analyses revealed that age and education at the
time of injury and mental health utilization prior to injury were significant
predictors of relationship change. Among those who were single/divorced/separated
at the time of enrollment, 87% remained so at year 2 while 13% underwent positive
change. Injury during deployment significantly predicted positive relationship
change. CONCLUSIONS: The unmalleable, preinjury characteristics identified may be
used as potential triggers for education, prevention, surveillance, and couples
therapy, if needed.
PMID- 28520675
TI - The Role of Cognitive Reserve in Recovery From Traumatic Brain Injury.
AB - OBJECTIVE: To examine whether cognitive reserve (CR) attenuates the initial
impact of traumatic brain injury (TBI) on cognitive performance (neural reserve)
and results in faster cognitive recovery rates in the first year postinjury
(neural compensation), and whether the advantage of CR differs on the basis of
the severity of TBI. SETTING: Inpatient/outpatient clinics at an academic medical
center. PARTICIPANTS: Adults with mild TBI (mTBI; n = 28), complicated mild TBI
(cmTBI; n = 24), and moderate to severe TBI (msevTBI; n = 57), and
demographically matched controls (n = 66). DESIGN: Retrospective, longitudinal
cohort assessed at 1, 6, and 12 months postinjury. MAIN MEASURES: Outcomes were 3
cognitive domains: processing speed/executive function, verbal fluency, and
memory. Premorbid IQ, estimated with the Wechsler Test of Adult Reading, served
as CR proxy. RESULTS: Higher premorbid IQ was associated with better performance
on cognitive domains at 1 month postinjury, and the effect of IQ was similarly
beneficial for all groups. Cognitive recovery rate was moderated only by TBI
severity; those with more severe TBI had faster recovery in the first year.
CONCLUSION: Results support only the neural reserve theory of CR within a TBI
population and indicate that CR is neuroprotective, regardless of the degree of
TBI. Higher premorbid CR does not allow for more rapid adaptation and recovery
from injury.
PMID- 28520678
TI - Anterior Cruciate Ligament Injury at the Time of Anterior Tibial Spine Fracture
in Young Patients: An Observational Cohort Study.
AB - BACKGROUND: Anterior tibial spine fractures (ATSF) in the skeletally immature
parallel anterior cruciate ligament (ACL) tears in adult patients, yet these
injuries are generally regarded as mutually exclusive. Biomechanical analysis
suggests that intrinsic ACL damage occurs during ATSF, and long-term clinical
studies demonstrate residual anteroposterior knee laxity following ATSF. We aim
to describe prevalence, demographics, and characteristics of pediatric patients
who sustained ATSF with concomitant ACL injury. METHODS: We included 129 patients
with ATSF over a 16-year period. Age, sex, injury mechanism, ATSF type, magnetic
resonance imaging (MRI) evaluation, treatment modality, ACL injury, and
concomitant meniscal/chondral injuries were analyzed. Concurrent ACL injury was
confirmed either from MRI or intraoperatively. RESULTS: Nineteen percent (n=25)
of ATSF patients had concomitant ACL injury, with ACL injury significantly more
likely in type II or type III ATSF compared with type I ATSF (P=0.03). Patients
with combined ATSF/ACL injury were significantly older (P=0.02) and more likely
to be male (P=0.01). Mechanism of ATSF injury was not associated with ACL injury
(P=0.83). Preoperative MRI had low sensitivity (0.09) for recognizing ACL injury
at the time of ATSF relative to intraoperative assessment. Half of ATSF/ACL
injured patients had additional meniscal or chondral injury, with meniscal repair
or debridement required in 37.5% of the type II ATSF/ACL injury. CONCLUSIONS:
There are demographic characteristics, such as age (older) and sex (male),
associated with a higher risk of concomitant ACL injury at the time of ATSF. Type
II and type III ATSF patterns had a higher prevalence of ACL injury. MRI failed
to correctly identify ACL injury at the time of ATSF. Concomitant ACL injury at
the time of ATSF is highly prevalent in the skeletally immature, occurring in
19.4% of patients with ATSF. LEVEL OF EVIDENCE: Level IV-case series.
PMID- 28520677
TI - The Use of an Electrophysiological Brain Function Index in the Evaluation of
Concussed Athletes.
AB - OBJECTIVE: To evaluate the effectiveness of the electroencephalographic (EEG)
Brain Function Index (BFI) for characterizing sports-related concussive injury
and recovery. PARTICIPANTS: Three hundred fifty-four (354) male contact sport
high school and college athletes were prospectively recruited from multiple
locations over 6 academic years of play (244 control baseline athletes and 110
athletes with a concussion). METHODS: Using 5 to 10 minutes of eyes closed
resting EEG collected from frontal and frontotemporal regions, a BFI was computed
for all subjects and sessions. Group comparisons were performed to test for the
significance of the difference in the BFI score between the controls at baseline
and athletes with a concussion at several time points. RESULTS: There was no
significant difference in BFI between athletes with a concussion at baseline (ie,
prior to injury) and controls at baseline (P = .4634). Athletes with a
concussion, tested within 72 hours of injury, exhibited significant differences
in BFI compared with controls (P = .0036). The significant differences in BFI
were no longer observed at 45 days following injury (P = .19). CONCLUSION:
Controls and athletes with a concussion exhibited equivalent BFI scores at
preseason baseline. The concussive injury (measured within 72 hours)
significantly affected brain function reflected in the BFI in the athletes with a
concussion. The BFI of the athletes with a concussion returned to levels seen in
controls by day 45, suggesting recovery. The BFI may provide an important
objective marker of concussive injury and recovery.
PMID- 28520679
TI - Knee Recurvatum in Children With Spastic Diplegic Cerebral Palsy.
AB - BACKGROUND: The purpose of this study is to determine which factors drive
patients with diplegic cerebral palsy to walk without knee recurvatum despite
hyperextension of the knee on physical examination. METHODS: A retrospective
review was conducted of all data collected in the Gait Analysis Laboratory
between 1999 and 2014. Patients with spastic diplegic cerebral palsy and at least
5 degrees of knee extension on clinical examination were identified for the
study. After IRB approval, a total of 60 children ranging in age from 4 to 17
were included in the study. There were 27 female patients. Gross Motor Function
Classification System level was distributed in the population as follows: 34
patients at Gross Motor Function Classification System level I, 18 at level II,
and 8 at level III. Patients were excluded from this study if they had
extrapyramidal involvement, history of selective dorsal rhizotomy or lower
extremity surgery. Patient who received botulinum toxin A injections within 1
year of the study were excluded as well. Patients were divided into 2 groups:
children that walked with knee hyperextension (KH) and children that walked
without knee hyperextension (KF, "knee flexion"). There were 15 subjects in the
KH group and 45 subjects in the KF group. Motion Laboratory evaluation included a
comprehensive examination, kinematics, and kinetic analysis with a VICOM system.
All data were analyzed with unpaired t test to detect differences between the 2
groups. All statistical analysis was done only for the right legs (unless the
right leg did not meet the exclusion then the left leg was analyzed) to meet the
statistical requirement for independence. The Pearson correlation was applied to
correlate the maximum knee extension in stance with maximum ankle dorsiflexion in
stance. RESULTS: The static measurement of dorsiflexion with knee flexed showed
statistically significant difference (P=0.004) with KH group having 2.3+/-11.6
degrees and KF group having 13.1+/-12.2 degrees. There was also a statistically
significant difference in the static measurement of dorsiflexion with knee
extended (P=0.0014) with KH group having -3.3+/-9.0 degrees and KF group having
5.8+/-9.1 degrees. Maximum dorsiflexion in stance phase also showed significant
difference (P=0.0022) with the KH group having 0.1+/-14.0 degrees and KF group
having 11.5+/-11.2 degrees. Maximum dorsiflexion in stance phase also showed
significant difference (P<0.001) with the DH group having 0.1 (SD) 14.0 degrees
and KF group having 11.5 (SD) 11.2 degrees. There were no significant differences
in popliteal angle measurements or any strength measurement. CONCLUSIONS: Our
study shows that the plantar flexion knee extension couple is the major
contributing factor to cause patients with passive knee hyperextension to walk in
a recurvatum pattern. This would have implications of further treatment of the
knee hyperextension in stance. LEVEL OF EVIDENCE: Level III-case-control study.
PMID- 28520680
TI - Acute Pediatric Monteggia Fractures: A Conservative Approach to Stabilization.
AB - BACKGROUND: In 2015, a multicenter study group proposed a treatment algorithm for
pediatric Monteggia fractures based upon the ulnar fracture pattern. This
strategy recommends surgical stabilization for all complete ulna fractures. The
purpose of this study was to evaluate whether an initial nonoperative approach to
pediatric Monteggia fractures resulted in poorer outcomes and a higher rate of
complications. METHODS: This institutional review board approved retrospective
study evaluated all Monteggia fractures presenting to a level 1 pediatric trauma
center between 2008 and 2014. Chart and radiographic reviews were performed on 94
patients who met inclusion criteria. The mean age was 5.5 years (range, 1 to 13
y). The mean clinical follow-up was 18 weeks. Major complications were defined as
those requiring an unplanned second procedure (other than implant removal) or
that may result in long-term disability (residual radial head
subluxation/dislocation). Univariate (P<0.05) and Multivariate Classification and
Regression Tree (CART) (P<0.05) analyses were used to identify variables
associated with the need for surgical stabilization. RESULTS: At final follow-up,
there were no cases of residual radiocapitellar joint subluxation or dislocation
and all fractures had healed. The majority (83%) of patients were successfully
managed with a cast. Univariate analysis found Bado type and maximum ulna
angulation as significant predictors (P<0.05), whereas the CART analysis found
ulna angulation >36.5 degrees as the only primary predictor of requiring surgical
stabilization. Overall, good outcomes were achieved in all patients with few
major complications. CONCLUSIONS: Although treatment algorithms are intended to
minimize complications and maximize good outcomes, we believe that an
unintentional consequence of the recently proposed pediatric Monteggia fracture
treatment guideline may be the overtreatment of these injuries. In our cohort,
the majority of patients were able to avoid the operating room and surgical
implants without compromising outcomes or complications. This more conservative
approach, however, requires close monitoring of patients in the first 3 weeks
during which most reductions were lost. LEVEL OF EVIDENCE: Level IV-therapeutic
studies, case series.
PMID- 28520681
TI - Delayed Dural Leak Following Posterior Spinal Fusion for Idiopathic Scoliosis
Using All Posterior Pedicle Screw Technique.
AB - BACKGROUND: In pediatric patients, pedicle screws are malpositioned 5% to 15% of
the time. Complications associated with malpositioned screws are infrequently
reported in the literature. We present a series of adolescent idiopathic
scoliosis (AIS) patients who presented in a delayed manner with positional
headache and chronic dural leak adjacent to the pedicle screw tract. METHODS:
Scoliosis databases at 2 centers were reviewed, and cases of delayed positional
headaches following posterior spinal fusion for AIS were identified. Demographic
and clinical data were collected. RESULTS: Of 322 patients, 4 patients presented
with positional headaches at a mean of 12.8 weeks following posterior spinal
fusion surgery for AIS, with an interval time to diagnosis of 5 months. Computed
tomographic myelogram demonstrated severe pedicle screw malposition in 1 patient,
and minimal malposition in 3 patients (<2 mm violation). The patients had delayed
presentation with positional headaches secondary to dural leak. All patients
successfully underwent revision surgery with repair of the dural leak. At the
time of latest follow-up, all patients are asymptomatic. CONCLUSIONS: Pedicle
screw malposition can result in dural leaks. Patients may present in a delayed
manner with positional headaches and an acquired Chiari malformation. Clinical
suspicion should prompt imaging of the brain or cervical spine followed by
computed tomographic myelogram to determine site of leak. This is a rare
complication from pedicle screw malposition. LEVELS OF EVIDENCE: Level IV-case
series.
PMID- 28520683
TI - Socioeconomic consequences of systemic lupus erythematosus.
AB - PURPOSE OF REVIEW: The present review addresses recent literature investigating
the socioeconomic consequences of systemic lupus erythematosus (SLE). We
highlight the latest updates on health disparities affecting the SLE population,
the direct and indirect economic costs of the disease, and less quantifiable
costs such as reduced health-related quality of life (HRQoL). RECENT FINDINGS:
Health disparities continue to exist among socially disadvantaged populations,
including African Americans, Hispanics, and patients with decreased educational
attainment and in poverty. Direct and indirect costs are substantial. Recent work
provides updated cost estimates for patients with SLE outside of North America,
including those in developing countries. Previous research has largely focused on
costs of the general SLE population and those with renal manifestations or active
SLE, whereas recent research addresses special populations such as hospitalized
and pregnant patients and glucocorticoid users. Patients with SLE and their
caregivers experience a substantially reduced HRQoL. SUMMARY: SLE is a costly
disease that disproportionately affects disadvantaged populations. Future
economic studies should measure not only direct costs, but also incorporate
indirect costs and the HRQoL of both patients with SLE and their caregivers. All
these components are essential to provide a comprehensive assessment of the
socioeconomic consequences of SLE and an appreciation of the potential impact of
novel therapies.
PMID- 28520682
TI - Progress in the pathogenesis and treatment of cardiac manifestations of neonatal
lupus.
AB - PURPOSE OF REVIEW: To provide new insights into pathogenesis, prevention and
management of cardiac manifestations of neonatal lupus (cardiac neonatal lupus)
and issues pertinent to all anti-SSA/Ro positive individuals of childbearing age.
RECENT FINDINGS: Antibody specificity with high risk for cardiac neonatal lupus
remains elusive, but high titers of Ro60, Ro52 or Ro52p200 antibodies appear to
be required. Varying antibody specificities to the p200 region of Ro52 can induce
first-degree block in a rodent model. In consideration of the contribution of
macrophages to inflammation and fibrosis in cardiac neonatal lupus,
hydroxychloroquine (HCQ) is being considered as preventive therapy. Cord blood
biomarkers support the association of fetal reactive inflammatory and fibrotic
components with the development and morbidity of cardiac neonatal lupus. Data
from U.S. and French registries do not provide evidence that the prompt use of
fluorinated steroids in cases of isolated block significantly alters
fetal/neonatal morbidity or mortality. SUMMARY: The search for a high-risk
cardiac neonatal lupus antibody profile remains, but high-titer antibodies to
Ro60 and R052 are a consistent finding, and this may guide the need for fetal
echocardiographic surveillance. The uniform use of fluorinated steroids to
prevent progression of cardiac neonatal lupus or reduce mortality does not appear
justified. HCQ, based on diminishing an inflammatory component of cardiac
neonatal lupus, is under consideration as a potential preventive approach.
PMID- 28520684
TI - Pediatric trauma undertriage in Ohio.
AB - BACKGROUND: Appropriate and timely triage is an essential component of a trauma
system. In the state of Ohio, there are 6 verified pediatric trauma centers
(PTCs) across 8 state regions. The purpose of this study was to better understand
the pediatric undertriage rates in the state. METHODS: We used the Ohio Trauma
Registry from 2007 to 2012, consisting of 14,045 records of children younger than
16 years admitted to a hospital for more than 48 hours or who sustained a
traumatic death. Pediatric undertriage was defined as not being directly
transported to a PTC when one was available within 30 minutes or not being
transferred to a PTC within 2 hours of injury. RESULTS: The state pediatric
undertriage rate was 52%, only decreasing to 35% when up to a 4-hour transfer
time was allowed. Across state trauma regions, undertriage rates varied from 94%
to 40%. More than 28% of injured children had access to a PTC within 30 minutes
of their home. A trauma center (adult or pediatric) was within 30 minutes for 66%
of the children, yet 32% of the children went to a nontrauma center first.
Overall, 29% of children never made it to a PTC, and 4% of children remained at a
nontrauma center, with regional variation from 5% to 0.5%. Statewide mortality
was nearly 3%, with regional variations between 5% and 0.4%. Mortality rate
within the appropriately triaged group was 5.3%, while mortality rate in the
undertriage group was only 0.7%. Overall, 53% of transferred patients had a more
than 2-hour transfer time. CONCLUSIONS: Despite the significant number of PTCs in
Ohio, there remains a high undertriage rate with significant regional variations
and long transfer times. Continued analysis will be useful in furthering trauma
system development for the injured child. LEVEL OF EVIDENCE: Therapeutic/care
management study, level IV; epidemiological, level IV.
PMID- 28520685
TI - Pelvic fracture pattern predicts the need for hemorrhage control intervention
Results of an AAST multi-institutional study.
AB - BACKGROUND: Early identification of patients with pelvic fractures at risk of
severe bleeding requiring intervention is critical. We performed a multi
institutional study to test our hypothesis that pelvic fracture patterns predict
the need for a pelvic hemorrhage control intervention. METHODS: This prospective,
observational, multicenter study enrolled patients with pelvic fracture due to
blunt trauma. Inclusion criteria included shock on admission (systolic blood
pressure <90 mm Hg or heart rate >120 beats/min and base deficit >5, and the
ability to review pelvic imaging). Demographic data, open pelvic fracture, blood
transfusion, pelvic hemorrhage control intervention (angioembolization, external
fixator, pelvic packing, and/or REBOA [resuscitative balloon occlusion of the
aorta]), and mortality were recorded. Pelvic fracture pattern was classified
according to Young-Burgess in a blinded fashion. Predictors of pelvic hemorrhage
control intervention and mortality were analyzed by univariate and multivariate
regression analyses. RESULTS: A total of 163 patients presenting in shock were
enrolled from 11 Level I trauma centers. The most common pelvic fracture pattern
was lateral compression I, followed by lateral compression I, and vertical shear.
Of the 12 patients with an anterior-posterior compression III fracture, 10 (83%)
required a pelvic hemorrhage control intervention. Factors associated with the
need for pelvic fracture hemorrhage control intervention on univariate analysis
included vertical shear pelvic fracture pattern, increasing age, and transfusion
of blood products. Anterior-posterior compression III fracture patterns and open
pelvic fracture predicted the need for pelvic hemorrhage control intervention on
multivariate analysis. Overall in-hospital mortality for patients admitted in
shock with pelvic fracture was 30% and did not differ based on pelvic fracture
pattern on multivariate analysis. CONCLUSION: Blunt trauma patients admitted in
shock with anterior-posterior compression III fracture patterns or patients with
open pelvic fracture are at greatest risk of bleeding requiring pelvic hemorrhage
control intervention. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level
III.
PMID- 28520686
TI - Clinical correlates to assist with chronic traumatic encephalopathy diagnosis:
Insights from a novel rodent repeat concussion model.
AB - INTRODUCTION: Chronic traumatic encephalopathy (CTE) is a neurodegenerative
disease linked to repetitive head injuries. Chronic traumatic encephalopathy
symptoms include changes in mood, behavior, cognition, and motor function;
however, CTE is currently diagnosed only postmortem. Using a rat model of
recurrent traumatic brain injury (TBI), we demonstrate rodent deficits that
predict the severity of CTE-like brain pathology. METHODS: Bilateral, closed
skull, mild TBI was administered once per week to 35 wild-type rats; eight rats
received two injuries (2*TBI), 27 rats received five injuries (5*TBI), and 13
rats were sham controls. To determine clinical correlates for CTE diagnosis, TBI
rats were separated based on the severity of rotarod deficits and classified as
"mild" or "severe" and further separated into "acute," "short," and "long" based
on age at euthanasia (90, 144, and 235 days, respectively). Brain atrophy,
phosphorylated tau, and inflammation were assessed. RESULTS: All eight 2*TBI
cases had mild rotarod deficiency, 11 5*TBI cases had mild deficiency, and 16
cases had severe deficiency. In one cohort of rats, tested at approximately 235
days of age, balance, rearing, and grip strength were significantly worse in the
severe group relative to both sham and mild groups. At the acute time period,
cortical thinning, phosphorylated tau, and inflammation were not observed in
either TBI group, whereas corpus callosum thinning was observed in both TBI
groups. At later time points, atrophy, tau pathology, and inflammation were
increased in mild and severe TBI groups in the cortex and corpus callosum,
relative to sham controls. These injury effects were exacerbated over time in the
severe TBI group in the corpus callosum. CONCLUSIONS: Our model of repeat mild
TBI suggests that permanent deficits in specific motor function tests correlate
with CTE-like brain pathology. Assessing balance and motor coordination over time
may predict CTE diagnosis.
PMID- 28520687
TI - 3% NaCl adenosine, lidocaine, Mg2+ (ALM) bolus and 4 hours "drip" infusion
reduces noncompressible hemorrhage by 60% in a rat model.
AB - BACKGROUND: Noncompressible torso hemorrhage is the leading cause of potentially
survivable trauma in far-forward combat environments. Our aim was to examine the
effect of small-volume 3% NaCl adenosine, lidocaine, and Mg (ALM) bolus and 0.9%
NaCl/ALM "drip" on survivability and cardiac/gut/kidney function in a rat model
of hepatic hemorrhage and shock. METHODS: Male Sprague-Dawley rats (428 +/- 4 g)
were anesthetized and randomly assigned to one of five groups (n = 16): (1) Sham,
(2) No treatment, (3) Saline controls, (4) ALM therapy, and (5) Hextend. Animals
were ventilated, instrumented with single or double laparotomy for tissue probe
insertion, and hemorrhage induced by liver resection. After 15 minutes, a single
3% NaCl +/- ALM bolus (0.7 ml/kg) was injected IV (phase 1) and after 60 minutes,
4 hours 0.9% NaCl +/- ALM stabilization "drip" (0.5 ml/kg/h) was administered
(phase 2), with 1-hour monitoring. RESULTS: Mortality for Shams (no resection)
was 0% (25%); No treatment, 87.5% (100%); Saline controls, 37.5% (75%); ALM
therapy, 0% (25%), and Hextend, 87.5% (100%) (double laparotomy in parentheses).
Hextend-treated animals died during the first 20 minutes of phase 2. A single ALM
bolus during phase 1 led to a 2.4-fold higher cardiac output and improved
hemodynamics. 3% NaCl ALM bolus increased tissue pO2 and flow in gut and kidney
during phase 1 and, during ALM "drip" in phase 2, tissue pO2 decreased but flow
continued to rise, indicating increased tissue O2 extraction and delivery. During
phase 2, CO, ejection fraction, and fractional shortening decreased and were
erratic in all groups except ALM treatment. ALM therapy led to up to 60% less
bleeding over 6 hours compared to Saline controls and 75% less bleeding than
Hextend. CONCLUSIONS: Small-volume ALM therapy significantly reduced mortality
and internal bleeding compared to Saline controls or Hextend-treated rats.
Hextend increased mortality, severe bleeding, and microvascular-organ injury.
PMID- 28520688
TI - The association of nonaccidental trauma with historical factors, examination
findings, and diagnostic testing during the initial trauma evaluation.
PMID- 28520689
TI - The course, prediction, and treatment of acute and posttraumatic stress in trauma
patients: A systematic review.
AB - BACKGROUND: Trauma patients suffer from acute stress disorder (ASD) and
posttraumatic stress disorder (PTSD), but it is unknown how these disorders
develop over time and when treatment is effective. Our aim was to systematically
review (1) the course and predictors of ASD and PTSD after trauma and (2) which
and when psychological treatments are effective. METHODS: Embase, Medline, Web of
Science, Scopus, PsycInfo, Cinahl, Cochrane, PubMed, and Google Scholar were
searched up to September 14, 2015. Quality was assessed with STROBE and CONSORT
checklists. RESULTS: Overall, 45 (68%) observational studies and 21 (32%)
intervention studies were included. Forty-seven (85%) were of lower (level of
evidence (LoE) 3) or poor quality (LoE 4). ASD was found during hospitalization
(range 1-37%) and about 30% experienced PTSD 1 month after trauma (LoE 3). The
onset of PTSD was within 3 months but also up to 12 months after trauma (LoE 3).
Especially in patients with ASD, patients showed PTSD symptoms after 6 years (LoE
3). ASD and PTSD were associated with sociodemographic factors (e.g., being
female, younger age, financial problems, and low income), reduced cognitive
functioning, and physical (e.g., pain), social (e.g., low social support), and
psychological problems (e.g., hyperarousal) or disorders (e.g., ASD). Early
treatment in the first weeks after trauma can be preventive for PTSD, but
effective treatment for ASD is still unclear. Compared to other psychological
treatments, the most effective and examined treatment for PTSD was cognitive
behavioral therapy (CBT). CONCLUSIONS: A large number of studies of lower or poor
quality present inconsistent findings on the course of ASD and PTSD. Predictors
for ASD and PTSD were identified. Early treatment can be preventive for PTSD, as
CBT is the most effective treatment. However, good qualitative observational and
intervention studies are lacking and needed. LEVEL OF EVIDENCE: Systematic
review, level III.
PMID- 28520690
TI - Managing grade 5 pancreatic injuries-Think smart, act smart, and call in the
pancreatic cavalry early.
PMID- 28520692
TI - Featured Articles for CME Credit June 2017.
PMID- 28520691
TI - Re: Managing grade V pancreatic injuries-Think smart, act smart, and call in the
pancreatic cavalry early.
PMID- 28520694
TI - Metabolic Inflammatory Complex in Sepsis: Septic Cachexia as a Novel Potential
Therapeutic Target.
AB - Despite several decades of focused investigation, sepsis remains a major cause of
mortality in critically ill patients. Advancements in intensive care have enabled
more patients to survive the acute phase of sepsis than previously, but a growing
number of them progress to chronic critical illness. The failure of previous
randomized clinical trials of anti-inflammatory agents to show any pro-survival
benefit in septic patients underscores current thought that simple anti
inflammatory strategies are ineffective because the inhibitory effect of anti
inflammatory agents undermines the immune response to pathogens. New strategies
with the dual capability of ameliorating inflammation in organs while stimulating
antimicrobial activity are eagerly awaited. On the other hand, the metabolic
alterations associated with systemic inflammatory response, including
mitochondrial dysfunction and metabolic shift, are closely linked through a nexus
of signaling pathways and signaling molecules. Preventing these metabolic
derangements may be an alternative way to control excessive inflammation, an
intriguing possibility that has not been fully explored. New insight into the
molecular pathogenesis of sepsis and sepsis-associated chronic critical illness
has led to the recognition of septic cachexia, a life-threatening form of
metabolic inflammatory complex associated with multiple organ dysfunction. The
potential for septic cachexia to serve as a novel target disease state to improve
the clinical outcome of septic patients is discussed in this review.
PMID- 28520695
TI - Calreticulin Ameliorates Hypoxia/Reoxygenation-Induced Human Microvascular
Endothelial Cell Injury By Inhibiting Autophagy.
AB - BACKGROUND: Autophagy has been found to be involved in myocardial
ischemia/reperfusion injury. However, the underlying mechanism and significance
of autophagy in reperfusion injury remain unclear. Herein, we evaluated the
effects of exogenous calreticulin (CRT) on autophagy in hypoxia/reoxygenation
(H/R)-treated human microvascular endothelial cells (MECs). METHODS: Human MECs
were pretreated with CRT (25 pg/mL) for 30 min, followed by exposure in an
incubator filled with a gas mixture of 90% N2, 5% O2, and 5% CO2 for 8-h hypoxia.
The cells were then placed back in the normoxic CO2 incubator for 16-h
reoxygenation. Cell injury was assessed by the cell counting kit-8 assay.
Autophagosomes were detected by transmission electron microscopy and
immunofluorescence staining. Western blot analysis was performed to detect
phosphorylated mammalian target of rapamycin (p-mTOR), Beclin 1, and microtubule
associated protein 1 light chain 3 (LC3). RESULTS: H/R induced marked autophagy
through the mTOR pathway. CRT suppressed rapamycin- and H/R-induced autophagosome
formation, the LC3-II/LC3-I ratio, and Beclin 1 expression in human MECs by
upregulating mTOR phosphorylation, consequently attenuating H/R-induced human MEC
injury. CONCLUSIONS: Exogenous CRT attenuated H/R-induced human MEC injury by
inhibiting autophagy.
PMID- 28520697
TI - Prescription drug prices in the US.
PMID- 28520696
TI - An Ovine Model of Hyperdynamic Endotoxemia and Vital Organ Metabolism.
AB - BACKGROUND: Animal models of endotoxemia are frequently used to understand the
pathophysiology of sepsis and test new therapies. However, important differences
exist between commonly used experimental models of endotoxemia and clinical
sepsis. Animal models of endotoxemia frequently produce hypodynamic shock in
contrast to clinical hyperdynamic shock. This difference may exaggerate the
importance of hypoperfusion as a causative factor in organ dysfunction. This
study sought to develop an ovine model of hyperdynamic endotoxemia and assess if
there is evidence of impaired oxidative metabolism in the vital organs. METHODS:
Eight sheep had microdialysis catheters implanted into the brain, heart, liver,
kidney, and arterial circulation. Shock was induced with a 4 h escalating dose
infusion of endotoxin. After 3 h vasopressor support was initiated with
noradrenaline and vasopressin. Animals were monitored for 12 h after endotoxemia.
Blood samples were recovered for hemoglobin, white blood cell count, creatinine,
and proinflammatory cytokines (IL-1Beta, IL-6, and IL-8). RESULTS: The endotoxin
infusion was successful in producing distributive shock with the mean arterial
pressure decreasing from 84.5 +/- 12.8 mm Hg to 49 +/- 8.03 mm Hg (P < 0.001).
Cardiac index remained within the normal range decreasing from 3.33 +/- 0.56
L/min/m to 2.89l +/- 0.36 L/min/m (P = 0.0845). Lactate/pyruvate ratios were not
significantly abnormal in the heart, brain, kidney, or arterial circulation.
Liver microdialysis samples demonstrated persistently high lactate/pyruvate
ratios (mean 37.9 +/- 3.3). CONCLUSIONS: An escalating dose endotoxin infusion
was successful in producing hyperdynamic shock. There was evidence of impaired
oxidative metabolism in the liver suggesting impaired splanchnic perfusion. This
may be a modifiable factor in the progression to multiple organ dysfunction and
death.
PMID- 28520698
TI - Valbenazine (Ingrezza) for tardive dyskinesia.
PMID- 28520699
TI - Oxymetazoline cream (Rhofade) for rosacea.
PMID- 28520700
TI - FDA warns against use of codeine and tramadol in children and breastfeeding
women.
PMID- 28520701
TI - Another subcutaneous immune globulin (Cuvitru) for primary immunodeficiency.
PMID- 28520702
TI - Vonvendi--recombinant von Willebrand factor.
PMID- 28520703
TI - Comparison table: some topical drugs for rosacea.
PMID- 28520704
TI - Adverse Events Associated with Treatment of Multidrug-Resistant Tuberculosis in
China: An Ambispective Cohort Study.
AB - BACKGROUND Adverse events are under-appreciated negative consequences that are
significant clinical problems for patients undergoing anti-MDR-TB treatment due
to longer duration of treatment and more need for concurrent use of multiple
second-line drugs. The aim of this study was to determine the incidence of
adverse events and their impact on MDR-TB therapy and treatment outcome, and to
identify possible drug-event pairs in China. MATERIAL AND METHODS An ambispective
cohort study was conducted based on hospital medical records, which included a
retrospective study that enrolled 751 MDR-TB patients receiving standardized
regimen between May 2009 and July 2013, and a follow-up investigation of
treatment outcome conducted in December 2016 in China. Adverse events were
determined according to laboratory results or clinical criteria. Cox's
proportional hazards regression models were used for evaluating associations.
RESULTS There were 681(90.7%) patients experienced at least 1 type of adverse
event and 55.2% of them required a changed MDR-TB treatment; 51(6.8%) patients
required permanent discontinuation of the offending drug due to adverse events.
The occurrence of adverse events was associated with poor treatment outcome
(adjusted hazard ratio, 1.54; 95% CI 1.21, 1.87). A total of 10 different drug
event pairs were identified. CONCLUSIONS Adverse events occurred commonly during
MDR-TB treatment in China, and often resulted in MDR-TB treatment change. The
occurrence of adverse events affected MDR-TB poor outcome after treatment.
PMID- 28520706
TI - QuickStats: Percentage* of Adults Aged >=65 Years Who Saw Selected Types of
Health Professionals? in the Past 12 Months, by Diagnosed Diabetes StatusS -
National Health Interview Survey, 2015.
AB - In 2015, adults aged >=65 years with diagnosed diabetes were more likely than
adults without diagnosed diabetes to report seeing general doctors (92.3%
compared with 86.7%); eye doctors (66.9% compared with 56.6%); physician
specialists (51.5% compared with 45.5%); foot doctors (29.9% compared with 13.0%)
and mental health professionals (6.3% compared with 4.5%) in the past 12 months.
Those with diabetes were less likely than those without diabetes to report seeing
a dentist or dental hygienist in the past 12 months (54.5% compared with 65.0%).
PMID- 28520705
TI - Disparities in Diabetes Deaths Among Children and Adolescents - United States,
2000-2014.
AB - Diabetes is a common chronic disease of childhood affecting approximately 200,000
children and adolescents in the United States (1). Children and adolescents with
diabetes are at increased risk for death from acute complications of diabetes,
including hypoglycemia and diabetic ketoacidosis (2,3); in 2012, CDC reported
that during 1968-2009, diabetes mortality among U.S. persons aged <=19 years
declined by 61% (4). CDC observed disparities by race during 1979-2004, with
black children and adolescents dying from diabetes at twice the rate of white
children and adolescents (5). However, no previous study has examined Hispanic
ethnicity. CDC analyzed data from the National Vital Statistics System for deaths
among persons aged 1-19 years in the United States during 2000-2014, with
diabetes listed as the underlying cause of death overall, and for Hispanic, non
Hispanic white (white), and non-Hispanic black (black) children and adolescents.
During 2012-2014, black children and adolescents had the highest diabetes death
rate (2.04 per 1 million population), followed by whites (0.92) and Hispanics
(0.61). There were no statistically significant changes in diabetes death rates
over the study period, but disparities persisted among racial/ethnic groups.
Death from diabetes in children and adolescents is potentially preventable
through increased awareness of diabetes symptoms (including symptoms of low blood
sugar), earlier treatment and education related to diabetes, and management of
diabetes ketoacidosis. Continued measures are needed to reduce diabetes mortality
in children and understand the cause of racial and ethnic disparities.
PMID- 28520707
TI - Using Molecular Characterization to Support Investigations of Aquatic Facility
Associated Outbreaks of Cryptosporidiosis - Alabama, Arizona, and Ohio, 2016.
AB - Cryptosporidiosis is a nationally notifiable gastrointestinal illness caused by
parasitic protozoa of the genus Cryptosporidium, which can cause profuse, watery
diarrhea that can last up to 2-3 weeks in immunocompetent patients and can lead
to life-threatening wasting and malabsorption in immunocompromised patients.
Fecal-oral transmission of Cryptosporidium oocysts, the parasite's infectious
life stage, occurs via ingestion of contaminated recreational water, drinking
water, or food, or following contact with infected persons or animals,
particularly preweaned bovine calves (1). The typical incubation period is 2-10
days. Since 2004, the annual incidence of nationally notified cryptosporidiosis
has risen approximately threefold in the United States (1). Cryptosporidium also
has emerged as the leading etiology of nationally notified recreational water
associated outbreaks, particularly those associated with aquatic facilities
(i.e., physical places that contain one or more aquatic venues [e.g., pools] and
support infrastructure) (2). As of February 24, 2017, a total of 13 (54%) of 24
states reporting provisional data detected at least 32 aquatic facility
associated cryptosporidiosis outbreaks in 2016. In comparison, 20 such outbreaks
were voluntarily reported to CDC via the National Outbreak Reporting System for
2011, 16 for 2012, 13 for 2013, and 16 for 2014. This report highlights
cryptosporidiosis outbreaks associated with aquatic facilities in three states
(Alabama, Arizona, and Ohio) in 2016. This report also illustrates the use of
CryptoNet, the first U.S. molecularly based surveillance system for a parasitic
disease, to further elucidate Cryptosporidium chains of transmission and
cryptosporidiosis epidemiology. CryptoNet data can be used to optimize evidence
based prevention strategies. Not swimming when ill with diarrhea is key to
preventing and controlling aquatic facility-associated cryptosporidiosis
outbreaks (https://www.cdc.gov/healthywater/swimming/swimmers/steps-healthy
swimming.html).
PMID- 28520708
TI - Hepatitis B Surface Antigen Screening Among Pregnant Women and Care of Infants of
Hepatitis B Surface Antigen-Positive Mothers - Guam, 2014.
AB - Hepatitis B virus (HBV) infection is endemic among adults in the U.S. territory
of Guam (1,2). Perinatal HBV transmission, which occurs at birth from an infected
mother to her newborn infant, is a major mode of HBV transmission and maintains
HBV endemicity (3). Approximately 90% of HBV-infected infants will develop
chronic HBV infection, and approximately 25% of those will die prematurely from
liver failure or hepatocellular carcinoma (4,5). Since 1988, the Advisory
Committee on Immunization Practices has recommended that all pregnant women be
screened for hepatitis B surface antigen (HBsAg), an indicator of HBV infection,
and that infants of women who screen positive (HBsAg-positive women) receive
postexposure prophylaxis (PEP) (hepatitis B vaccine and hepatitis B
immunoglobulin [HBIG]). When received within 12 hours of birth, PEP is 85%-95%
effective in preventing perinatal HBV transmission (5,6). Hepatitis B vaccine
provides long-term active immunity to HBV infection and HBIG provides short-term
passive immunity to HBV infection until the infant responds to the vaccine (5).
Hepatitis B vaccine was introduced into the routine universal infant vaccination
schedule in Guam in 1988 (1).
PMID- 28520709
TI - Updated Recommendations for Use of MenB-FHbp Serogroup B Meningococcal Vaccine -
Advisory Committee on Immunization Practices, 2016.
AB - Two serogroup B meningococcal (MenB) vaccines are currently licensed for use in
persons aged 10-25 years in the United States. The two vaccines are MenB-FHbp
(Trumenba, Pfizer, Inc.) (1) and MenB-4C (Bexsero, GlaxoSmithKline Biologicals,
Inc.) (2). In February 2015, the Advisory Committee on Immunization Practices
(ACIP) recommended use of MenB vaccines among certain groups of persons aged >=10
years who are at increased risk for serogroup B meningococcal disease* (Category
A) (3), and in June 2015, ACIP recommended that adolescents and young adults aged
16-23 years may be vaccinated with MenB vaccines to provide short-term protection
against most strains of serogroup B meningococcal disease (Category B?) (4).
Consistent with the original Food and Drug Administration (FDA) licensure for the
two available MenB vaccines, ACIP recommended either a 3-dose series of MenB-FHbp
or a 2-dose series of MenB-4C. Either MenB vaccine can be used when indicated;
ACIP does not state a product preference. The two MenB vaccines are not
interchangeable; the same vaccine product must be used for all doses in a series.
In April 2016, changes to the dosage and administration of MenB-FHbp were
approved by FDA to allow for both a 2-dose series (administered at 0 and 6
months) and a 3-dose series (administered at 0, 1-2, and 6 months) (5,6). In
addition, the package insert now states that the choice of dosing schedule
depends on the patient's risk for exposure and susceptibility to serogroup B
meningococcal disease. These recommendations are regarding use of the 2- and 3
dose schedules of MenB-FHbp vaccine (Trumenba) and replace previous ACIP
recommendations for use of MenB-FHbp vaccine published in 2015 (3,4).
Recommendations regarding use of MenB-4C (Bexsero) are unchanged (3,4).
PMID- 28520710
TI - Notes from the Field: Ongoing Transmission of Candida auris in Health Care
Facilities - United States, June 2016-May 2017.
PMID- 28520711
TI - Inhalational Chlorine Injuries at Public Aquatic Venues - California, 2008-2015.
AB - In June 2015, personnel from California's Contra Costa Health Services
Environmental Health and Hazardous Materials (hazmat) divisions were alerted to a
possible chemical release at a swimming pool in an outdoor municipal water park.
Approximately 50 bathers were in the pool when symptoms began; 34 (68%)
experienced vomiting, coughing, or eye irritation. Among these persons, 17 (50%)
were treated at the scene by Contra Costa's Emergency Medical Services (EMS) and
released, and 17 (50%) were transported to local emergency departments; five
patients also were evaluated later at an emergency department or by a primary
medical provider. Environmental staff members determined that a chemical
controller malfunction had allowed sodium hypochlorite and muriatic acid
(hydrochloric acid) solutions to be injected into the main pool recirculation
line while the recirculation pump was off; when the main recirculation pump was
restarted, toxic chlorine gas (generated by the reaction of concentrated sodium
hypochlorite and muriatic acid) was released into the pool. A review of 2008-2015
California pesticide exposure records identified eight additional such instances
of toxic chlorine gas releases at public aquatic venues caused by equipment
failure or human error that sickened 156 persons. Chemical exposures at public
aquatic venues can be prevented by proper handling, storage, and monitoring of
pool chemicals; appropriate equipment operation and maintenance; training of pool
operators and staff members on pool chemical safety; and reporting of chemical
exposures.
PMID- 28520712
TI - Announcement: World IBD Day - May 19, 2017.
AB - World IBD Day is recognized on May 19 to raise awareness of inflammatory bowel
disease (IBD) and the two conditions that comprise it: Crohn's disease and
ulcerative colitis, both of which cause chronic inflammation of the
gastrointestinal tract. World IBD Day is sponsored by the European Federation of
Crohn's and Ulcerative Colitis Associations, which includes the Crohn's & Colitis
Foundation.
PMID- 28520714
TI - Alteration of stream temperature by natural and artificial beaver dams.
AB - Beaver are an integral component of hydrologic, geomorphic, and biotic processes
within North American stream systems, and their propensity to build dams alters
stream and riparian structure and function to the benefit of many aquatic and
terrestrial species. Recognizing this, beaver relocation efforts and/or
application of structures designed to mimic the function of beaver dams are
increasingly being utilized as effective and cost-efficient stream and riparian
restoration approaches. Despite these verities, the notion that beaver dams
negatively impact stream habitat remains common, specifically the assumption that
beaver dams increase stream temperatures during summer to the detriment of
sensitive biota such as salmonids. In this study, we tracked beaver dam
distributions and monitored water temperature throughout 34 km of stream for an
eight-year period between 2007 and 2014. During this time the number of natural
beaver dams within the study area increased by an order of magnitude, and an
additional 4 km of stream were subject to a restoration manipulation that
included installing a high-density of Beaver Dam Analog (BDA) structures designed
to mimic the function of natural beaver dams. Our observations reveal several
mechanisms by which beaver dam development may influence stream temperature
regimes; including longitudinal buffering of diel summer temperature extrema at
the reach scale due to increased surface water storage, and creation of cool
water channel scale temperature refugia through enhanced groundwater-surface
water connectivity. Our results suggest that creation of natural and/or
artificial beaver dams could be used to mitigate the impact of human induced
thermal degradation that may threaten sensitive species.
PMID- 28520713
TI - Combining inferred regulatory and reconstructed metabolic networks enhances
phenotype prediction in yeast.
AB - Gene regulatory and metabolic network models have been used successfully in many
organisms, but inherent differences between them make networks difficult to
integrate. Probabilistic Regulation Of Metabolism (PROM) provides a partial
solution, but it does not incorporate network inference and underperforms in
eukaryotes. We present an Integrated Deduced And Metabolism (IDREAM) method that
combines statistically inferred Environment and Gene Regulatory Influence Network
(EGRIN) models with the PROM framework to create enhanced metabolic-regulatory
network models. We used IDREAM to predict phenotypes and genetic interactions
between transcription factors and genes encoding metabolic activities in the
eukaryote, Saccharomyces cerevisiae. IDREAM models contain many fewer
interactions than PROM and yet produce significantly more accurate growth
predictions. IDREAM consistently outperformed PROM using any of three popular
yeast metabolic models and across three experimental growth conditions.
Importantly, IDREAM's enhanced accuracy makes it possible to identify subtle
synthetic growth defects. With experimental validation, these novel genetic
interactions involving the pyruvate dehydrogenase complex suggested a new role
for fatty acid-responsive factor Oaf1 in regulating acetyl-CoA production in
glucose grown cells.
PMID- 28520715
TI - Geographical distribution of complement receptor type 1 variants and their
associated disease risk.
AB - BACKGROUND: Pathogens exert selective pressure which may lead to substantial
changes in host immune responses. The human complement receptor type 1 (CR1) is
an innate immune recognition glycoprotein that regulates the activation of the
complement pathway and removes opsonized immune complexes. CR1 genetic variants
in exon 29 have been associated with expression levels, C1q or C3b binding and
increased susceptibility to several infectious diseases. Five distinct CR1
nucleotide substitutions determine the Knops blood group phenotypes, namely
Kna/b, McCa/b, Sl1/Sl2, Sl4/Sl5 and KCAM+/-. METHODS: CR1 variants were genotyped
by direct sequencing in a cohort of 441 healthy individuals from Brazil, Vietnam,
India, Republic of Congo and Ghana. RESULTS: The distribution of the CR1 alleles,
genotypes and haplotypes differed significantly among geographical settings
(p<=0.001). CR1 variants rs17047660A/G (McCa/b) and rs17047661A/G (Sl1/Sl2) were
exclusively observed to be polymorphic in African populations compared to the
groups from Asia and South-America, strongly suggesting that these two SNPs may
be subjected to selection. This is further substantiated by a high linkage
disequilibrium between the two variants in the Congolese and Ghanaian
populations. A total of nine CR1 haplotypes were observed. The CR1*AGAATA
haplotype was found more frequently among the Brazilian and Vietnamese study
groups; the CR1*AGAATG haplotype was frequent in the Indian and Vietnamese
populations, while the CR1*AGAGTG haplotype was frequent among Congolese and
Ghanaian individuals. CONCLUSION: The African populations included in this study
might have a selective advantage conferred to immune genes involved in pathogen
recognition and signaling, possibly contributing to disease susceptibility or
resistance.
PMID- 28520717
TI - Modular Protein Expression Toolbox (MoPET), a standardized assembly system for
defined expression constructs and expression optimization libraries.
AB - The design and generation of an optimal expression construct is the first and
essential step in in the characterization of a protein of interest. Besides
evaluation and optimization of process parameters (e.g. selection of the best
expression host or cell line and optimal induction conditions and time points),
the design of the expression construct itself has a major impact. However, the
path to this final expression construct is often not straight forward and
includes multiple learning cycles accompanied by design variations and retesting
of construct variants, since multiple, functional DNA sequences of the expression
vector backbone, either coding or non-coding, can have a major impact on
expression yields. To streamline the generation of defined expression constructs
of otherwise difficult to express proteins, the Modular Protein Expression
Toolbox (MoPET) has been developed. This cloning platform allows highly efficient
DNA assembly of pre-defined, standardized functional DNA modules with a minimal
cloning burden. Combining these features with a standardized cloning strategy
facilitates the identification of optimized DNA expression constructs in shorter
time. The MoPET system currently consists of 53 defined DNA modules divided into
eight functional classes and can be flexibly expanded. However, already with the
initial set of modules, 792,000 different constructs can be rationally designed
and assembled. Furthermore, this starting set was used to generate small and mid
sized combinatorial expression optimization libraries. Applying this screening
approach, variants with up to 60-fold expression improvement have been identified
by MoPET variant library screening.
PMID- 28520716
TI - Expected population weight and diabetes impact of the 1-peso-per-litre tax to
sugar sweetened beverages in Mexico.
AB - STUDY QUESTION: What effect on body mass index, obesity and diabetes can we
expect from the 1-peso-per-litre tax to sugar sweetened beverages in Mexico?
METHODS: Using recently published estimates of the reductions in beverage
purchases due to the tax, we modelled its expected long-term impacts on body mass
index (BMI), obesity and diabetes. Microsimulations based on a nationally
representative dataset were used to estimate the impact of the tax on BMI and
obesity. A Markov population model, built upon an age-period-cohort model of
diabetes incidence, was used to estimate the impact on diagnosed diabetes in
Mexico. To analyse the potential of tax increases we also modelled a 2-peso-per
litre tax scenario. STUDY ANSWER AND LIMITATIONS: Ten years after the
implementation of the tax, we expect an average reduction of 0.15 kg/m2 per
person, which translates into a 2.54% reduction in obesity prevalence. People in
the lowest level of socioeconomic status and those between 20 and 35 years of age
showed the largest reductions in BMI and overweight and obesity prevalence.
Simulations show that by 2030, under the current implementation of 1-peso-per
litre, the tax would prevent 86 to 134 thousand cases of diabetes. Overall, the 2
peso-per-litre scenario is expected to produce twice as much of a reduction.
These estimates assume the tax effect on consumption remains stable over time.
Sensitivity analyses were conducted to assess the robustness of findings; similar
results were obtained with various parameter assumptions and alternative
modelling approaches. WHAT THIS STUDY ADDS: The sugar-sweetened beverages tax in
Mexico is expected to produce sizable and sustained reductions in obesity and
diabetes. Increasing the tax could produce larger benefits. While encouraging,
estimates will need to be updated once data on direct changes in consumption
becomes available.
PMID- 28520718
TI - Retrospective observational evaluation of postoperative oxygen saturation levels
and associated postoperative respiratory complications and hospital resource
utilization.
AB - INTRODUCTION: The clinical importance of postoperative episodic hypoxemia is
still unclear, and therefore largely under-studied. As a result, there is limited
understanding of its relationship with early postoperative respiratory
complications (PRC, defined as intubation within three days of surgery) and
hospital resource utilization. MATERIALS AND METHODS: This single center study
was performed using a retrospective observational design. We described population
based definitions of desaturation from continuous SpO2 monitoring data captured
in the post anesthesia care unit (PACU), namely median SpO2 in PACU, duration of
desaturation below median, nadir desaturation, and length of oxygen therapy
relative to PACU duration. These measures were evaluated against the occurrence
of early PRC in logistic regression models. Measures that were independently
associated with early PRC were accepted as the primary study exposures.
Stratified logistic regression models were planned if significant interaction
occurred with high risk surgical procedures. Models were adjusted by including
several patient conditions, procedural, and anesthesia risk factors. Propensity
matching on desaturation occurrence was planned to evaluate the relationship with
postoperative resource utilization. RESULTS: Among 125,740 patients included in
the univariate analyses, 351 patients (0.3%) developed early PRC. Nadir
desaturation <89% [14.3% of patients; adjusted odds ratio 2.02; 95% CI 1.52,
2.68; p<0.001] and PACU oxygen therapy requirements greater than 60 min [adjusted
odds ratio 1.92 (>60 min) to 3.04 (>90 min); p<0.001] were identified as
independent predictors of early PRC occurrence. A modest interaction was observed
between desaturation and higher surgical risk. Propensity matching for
postoperative oxygen requirement was performed in 37,354 matched patients.
Matched analysis demonstrated significant increase in day of surgery charges,
respiratory charges, total charges, hospital length of stay, reintubation and use
of invasive or non-invasive ventilatory support. CONCLUSIONS: In summary, we
report that prolonged PACU oxygen therapy and nadir desaturation <89% in PACU as
captured in a retrospective database are independently associated with early PRC.
This study describes resource implications of PACU desaturation in a large
academic medical center in North America.
PMID- 28520719
TI - Sex differences in management and outcomes of patients with atrial fibrillation
in the Middle East: Gulf survey of atrial fibrillation events (Gulf SAFE).
AB - Differences in the management of atrial fibrillation (AF) between men and women
were investigated by using Gulf SAFE data in the Middle East. The study included
2,043 patients presenting with AF to emergency room (ER) were prospectively
enrolled and followed for one-year. Women were older, have higher body mass index
(BMI), comorbidities, and health complications than men. With regard to
management of AF, cardioversion was recommended more often for men (16.7% vs.
9.3%), and underwent electrical cardioversion (2.2% vs. 1.1%). Women were
prescribed digoxin more frequently than men (25.6% vs. 17.4%) and a significant
number women received warfarin alone (31.1% vs. 8.7%). No difference between the
sexes was noticed in One-year rates of stroke/transient ischemic attacks (TIA)
and all-cause of mortality after one-year follow-up (3.1% men vs. 3.3% women, and
7.5% vs. 7.4%). Older age (>= 65 years), smoking, alcohol use, CHADS2 scores >=5
were some of the significant risk factors in men with AF. Suboptimal use of
anticoagulants, higher mortality and stroke/TIA events at one year are high but
similar between the sexes. ER management revealed high use of rate control
strategy and high rate of hospital admission was noticed in women.
PMID- 28520721
TI - On the slope of the regression between stem cell divisions and cancer risk, and
the lack of correlation between stem cell divisions and environmental factors
associated cancer risk.
PMID- 28520720
TI - Identification of human short introns.
AB - Canonical pre-mRNA splicing requires snRNPs and associated splicing factors to
excise conserved intronic sequences, with a minimum intron length required for
efficient splicing. Non-canonical splicing-intron excision without the
spliceosome-has been documented; most notably, some tRNAs and the XBP1 mRNA
contain short introns that are not removed by the spliceosome. There have been
some efforts to identify additional short introns, but little is known about how
many short introns are processed from mRNAs. Here, we report an approach to
identify RNA short introns from RNA-Seq data, discriminating against small
genomic deletions. We identify hundreds of short introns conserved among multiple
human cell lines. These short introns are often alternatively spliced and are
found in a variety of RNAs-both mRNAs and lncRNAs. Short intron splicing
efficiency is increased by secondary structure, and we detect both canonical and
non-canonical short introns. In many cases, splicing of these short introns from
mRNAs is predicted to alter the reading frame and change protein output. Our
findings imply that standard gene prediction models which often assume a lower
limit for intron size fail to predict short introns effectively. We conclude that
short introns are abundant in the human transcriptome, and short intron splicing
represents an added layer to mRNA regulation.
PMID- 28520722
TI - Altered detrusor contractility in MPTP-treated common marmosets with bladder
hyperreflexia.
AB - Bladder hyperreflexia is a common non-motor feature of Parkinson's disease. We
now report on the contractility of the isolated primate detrusor strips devoid of
nerve input and show that following MPTP, the amplitude and frequency of
spontaneous contraction was increased. These responses were unaffected by
dopamine D1 and D2 receptor agonists A77636 and ropinirole respectively.
Contractions by exogenous carbachol, histamine or ATP were similar and no
differences in the magnitude of noradrenaline-induced relaxation were seen in
detrusor strip obtained from normal and MPTP-treated common marmosets (Callithrix
jacchus). However, the neurogenic contractions following electrical field
stimulation of the intrinsic nerves (EFS) were markedly greater in strips
obtained from MPTP treated animals. EFS evoked non-cholinergic contractions
following atropine were also greater but the contribution of the cholinergic
innervation as a proportion of the overall contraction was smaller in the
detrusor strips of MPTP treated animals, suggesting a preferential enhancement of
the non-cholinergic transmission. Although dopaminergic mechanism has been
proposed to underlie bladder hyperreflexia in MPTP-treated animals with intact
bladder, the present data indicates that the increased neurogenically mediated
contractions where no extrinsic innervation exists might be due to long-term
adaptive changes locally as a result of the loss of the nigrostriatal output.
PMID- 28520723
TI - Follicular size predicts success in artificial insemination with frozen-thawed
sperm in donkeys.
AB - In asses, semen collection, cryopreservation, and artificial insemination (AI)
with frozen-thawed semen have been scarcely described and success rate,
particularly following AI, is reportedly low. In the absence of reliable
protocols, assisted reproductive technologies cannot support the conservation
efforts aimed at endangered wild ass species and domestic donkey breeds. Two
experiments were conducted in this study. In experiment 1 we evaluated freezing
Abyssinian donkey (N = 5, 4 ejaculates each) spermatozoa using three freezing
extenders (Berliner Cryomedium + glycerol, BC+G; BotuCrio, BOTU; INRAFreeze,
INRA) and two cryopreservation techniques (liquid nitrogen vapour, LNV;
directional freezing, DF). Post-thaw evaluation indicated that BOTU and INRA were
similar and both superior to BC+G (P <= 0.004 for all motility tests), and that
DF was superior to LNV (P < 0.002 for all evaluation parameters). In experiment
2, relying on these results, we used Abyssinian donkey sperm frozen in BOTU and
INRA by DF for AI (N = 20). Prior to AI, thawed samples were diluted in
corresponding centrifugation media or autologous seminal fluids at 1:1 ratio. No
difference was found between BOTU and INRA or between the addition of seminal
fluids or media, all resulting in ~50% pregnancy, and no differences were noted
between males (N = 4). The size of pre-ovulatory follicle was a significant (P =
0.001) predictor for AI success with 9/10 pregnancies occurring when follicular
size ranged between 33.1-37.4 mm, no pregnancy when it was smaller, and only one
when larger. A number of ass species face the risk of extinction. Knowledge
gained in this study on the Abyssinian donkey can be customised and transferred
to its closely related endangered species and breeds.
PMID- 28520724
TI - Development of a movement-based in vitro screening assay for the identification
of new anti-cestodal compounds.
AB - Intestinal cestodes are infecting millions of people and livestock worldwide, but
treatment is mainly based on one drug: praziquantel. The identification of new
anti-cestodal compounds is hampered by the lack of suitable screening assays. It
is difficult, or even impossible, to evaluate drugs against adult cestodes in
vitro due to the fact that these parasites cannot be cultured in microwell
plates, and adult and larval stages in most cases represent different organisms
in terms of size, morphology, and metabolic requirements. We here present an in
vitro-drug screening assay based on Echinococcus multilocularis protoscoleces,
which represent precursors of the scolex (hence the anterior part) of the adult
tapeworm. This movement-based assay can serve as a model for an adult cestode
screen. Protoscoleces are produced in large numbers in Mongolian gerbils and
mice, their movement is measured and quantified by image analysis, and active
compounds are directly assessed in terms of morphological effects. The use of the
384-well format minimizes the amount of parasites and compounds needed and allows
rapid screening of a large number of chemicals. Standard drugs showed the
expected dose-dependent effect on movement and morphology of the protoscoleces.
Interestingly, praziquantel inhibited movement only partially within 12 h of
treatment (at concentrations as high as 100 ppm) and did thus not act
parasiticidal, which was also confirmed by trypan blue staining. Enantiomers of
praziquantel showed a clear difference in their minimal inhibitory concentration
in the motility assay and (R)-(-)-praziquantel was 185 times more active than (S)
(-)-praziquantel. One compound named MMV665807, which was obtained from the open
access MMV (Medicines for Malaria Venture) Malaria box, strongly impaired
motility and viability of protoscoleces. Corresponding morphological alterations
were visualized by scanning electron microscopy, and demonstrated that this
compound exhibits a mode of action clearly distinct from praziquantel. Thus,
MMV665807 represents an interesting lead for further evaluation.
PMID- 28520726
TI - Losing a jewel-Rapid declines in Myanmar's intact forests from 2002-2014.
AB - New and rapid political and economic changes in Myanmar are increasing the
pressures on the country's forests. Yet, little is known about the past and
current condition of these forests and how fast they are declining. We mapped
forest cover in Myanmar through a consortium of international organizations and
environmental non-governmental groups, using freely-available public domain data
and open source software tools. We used Landsat satellite imagery to assess the
condition and spatial distribution of Myanmar's intact and degraded forests with
special focus on changes in intact forest between 2002 and 2014. We found that
forests cover 42,365,729 ha or 63% of Myanmar, making it one of the most forested
countries in the region. However, severe logging, expanding plantations, and
degradation pose increasing threats. Only 38% of the country's forests can be
considered intact with canopy cover >80%. Between 2002 and 2014, intact forests
declined at a rate of 0.94% annually, totaling more than 2 million ha forest
loss. Losses can be extremely high locally and we identified 9 townships as
forest conversion hotspots. We also delineated 13 large (>100,000 ha) and
contiguous intact forest landscapes, which are dispersed across Myanmar. The
Northern Forest Complex supports four of these landscapes, totaling over 6.1
million ha of intact forest, followed by the Southern Forest Complex with three
landscapes, comprising 1.5 million ha. These remaining contiguous forest
landscape should have high priority for protection. Our project demonstrates how
open source data and software can be used to develop and share critical
information on forests when such data are not readily available elsewhere. We
provide all data, code, and outputs freely via the internet at (for scripts:
https://bitbucket.org/rsbiodiv/; for the data:
http://geonode.themimu.info/layers/geonode%3Amyan_lvl2_smoothed_dec2015_resamp).
PMID- 28520725
TI - Reading positional codes with fMRI: Problems and solutions.
AB - Neural mechanisms which bind items into sequences have been investigated in a
large body of research in animal neurophysiology and human neuroimaging. However,
a major problem in interpreting this data arises from a fact that several
unrelated processes, such as memory load, sensory adaptation, and reward
expectation, also change in a consistent manner as the sequence unfolds. In this
paper we use computational simulations and data from two fMRI experiments to show
that a host of unrelated neural processes can masquerade as sequence
representations. We show that dissociating such unrelated processes from a
dedicated sequence representation is an especially difficult problem for fMRI
data, which is almost exclusively the modality used in human experiments. We
suggest that such fMRI results must be treated with caution and in many cases the
assumed neural representation might actually reflect unrelated processes.
PMID- 28520727
TI - Predictors of decision ambivalence and the differences between actual living
liver donors and potential living liver donors.
AB - BACKGROUND: The decision to become a living liver donor is a stressful event.
Ambivalence in decision making may result in psychological distress. Thus, the
purpose of this study was to provide a description of the ambivalence of
potential living liver donors, to examine the predictors of ambivalence, and to
compare the ambivalence of potential living liver donors with that of actual
living liver donors. METHODS: This descriptive and correlational study was
conducted in a medical center from August 2013 to December 2015. Self-reported
questionnaires were used to collect data. A total of 263 potential living liver
donors who were assessed for donation to their parents were included in this
study. RESULTS: The mean age of the total sample was 30.7 years (SD = 6.39, range
= 20-47), and males comprised 53.6% of the sample. The majority of the potential
donors had a college education (70.8%) and were single (63.5%). Of the total
sample, the mean score for ambivalence was 4.27 (SD = 1.87, range = 0-7).
Multivariate analysis revealed that the Mental Component Summary (MCS) of quality
of life (beta = -0.24, p < 0.01), family support (beta = -0.17, p = 0.007), and
intimacy (beta = -0.13, p = 0.04) were significant protective predictors of
ambivalence. Actual living liver donors had significantly lower ambivalence (3.82
versus 4.60), higher intimacy with recipients (3.55 versus 3.34), higher MCS
(45.26 versus 42.80), and higher family support (34.39 versus 29.79) than did the
remaining potential living liver donors. CONCLUSION: Ambivalence is common in
potential living liver donors. The MCS of quality of life, family support, and
intimacy were protective predictors in terms of ambivalence. Future research
should explore other factors and design interventions targeted toward reducing
ambivalence, promoting family support, and enhancing the mental dimensions of
quality of life in potential living liver donors.
PMID- 28520728
TI - Cost-effectiveness of hepatitis C treatment using generic direct-acting
antivirals available in India.
AB - BACKGROUND & AIMS: Availability of directly-acting antivirals (DAAs) has changed
the treatment landscape of hepatitis C virus (HCV) infection. The high price of
DAAs has restricted their use in several countries. However, in some countries
such as India, generic DAAs are available at much cheaper price. This study
examined whether generic DAAs could be cost-saving and how long it would take for
the treatment to become cost-saving/effective. METHODS: A previously-validated,
mathematical model was adapted to the HCV-infected population in India to compare
the outcomes of no treatment versus treatment with DAAs. Model parameters were
estimated from published studies. Cost-effectiveness of HCV treatment using
available DAAs was calculated, using a payer's perspective. We estimated quality
adjusted life years (QALYs), disability-adjusted life years (DALYs), total costs,
and incremental cost-effectiveness ratio of DAAs versus no treatment. One-way and
probabilistic sensitivity analyses were conducted. RESULTS: Compared with no
treatment, the use of generic DAAs in Indian HCV patients would increase the life
expectancy by 8.02 years, increase QALYs by 3.89, avert 19.07 DALYs, and reduce
the lifetime healthcare costs by $1,309 per-person treated. Treatment became cost
effective within 2 years, and cost-saving within 10 years of its initiation
overall and within 5 years in persons with cirrhosis. Treating 10,000 HCV
infected persons could prevent 3400-3850 decompensated cirrhosis, 1800-2500 HCC,
and 4000-4550 liver-related deaths. The results were sensitive to the costs of
DAAs, pre- and post-treatment diagnostic tests and management of cirrhosis, and
quality of life after sustained virologic response. CONCLUSIONS: Treatment with
generic DAAs available in India will improve patient outcomes, provide a good
value for money within 2 years, and be ultimately cost-saving. Therefore, in this
and similar settings, HCV treatment should be a priority from a public health as
well an economic perspective.
PMID- 28520729
TI - Top quality blastocyst formation rates in relation to progesterone levels on the
day of oocyte maturation in GnRH antagonist IVF/ICSI cycles.
AB - Cycles with progesterone elevation during controlled ovarian stimulation (COS)
for IVF/ICSI are commonly managed with a "freeze-all" strategy, due to a well
recognized detrimental effect of high progesterone levels on endometrial
receptivity. However, also a detrimental effect of elevated progesterone on day-3
embryo quality has recently been found with regards to top quality embryo
formation rate. Because blastocyst culture and cryopreservation are largely
adopted, we deemed relevant to determine whether this detrimental effect is also
seen on blastocyst quality on day 5-6. This issue was investigated through a
large two-center retrospective study including 986 GnRH antagonist IVF/ICSI
cycles and using top quality blastocyst formation rate as the main outcome.
Results showed that on multivariate analysis sperm motility (p<0.01) and
progesterone levels at ovulation triggering (p = 0.01) were the only two
variables that significantly predicted top quality blastocyst formation rate
after adjusting for relevant factors including female age, BMI, basal AMH and
total dose of FSH used for COS. More specifically, progesterone levels at
induction showed an inverse relation with top quality blastocyst formation
(correlation coefficient B = -1.08, 95% CI -1.9 to -0.02) and ROC curve analysis
identified P level >1.49 ng/ml as the best cut-off for identification of patients
at risk for the absence of top quality blastocysts (AUC 0.55, p<0.01). Our study
is the first to investigate the top quality blastocyst formation rate in relation
to progesterone levels in IVF/ICSI cycles, showing that increasing progesterone
is associated with lower rates of top quality blastocyst. Hence, the advantages
of prolonging COS to maximize the number of collected oocytes might eventually be
hindered by a decrease in top quality blastocysts available for transfer, if
increasing progesterone levels are observed. This observation extends the results
of two recent studies focused on day-3 embryos and deserves further research.
PMID- 28520731
TI - Genetically engineered probiotic for the treatment of phenylketonuria (PKU);
assessment of a novel treatment in vitro and in the PAHenu2 mouse model of PKU.
AB - Phenylketonuria (PKU) is a genetic disease characterized by the inability to
convert dietary phenylalanine to tyrosine by phenylalanine hydroxylase. Given the
importance of gut microbes in digestion, a genetically engineered microbe could
potentially degrade some ingested phenylalanine from the diet prior to
absorption. To test this, a phenylalanine lyase gene from Anabaena variabilis
(AvPAL) was codon-optimized and cloned into a shuttle vector for expression in
Lactobacillus reuteri 100-23C (pHENOMMenal). Functional expression of AvPAL was
determined in vitro, and subsequently tested in vivo in homozygous PAHenu2 (PKU
model) mice. Initial trials of two PAHenu2 homozygous (PKU) mice defined
conditions for freeze-drying and delivery of bacteria. Animals showed reduced
blood phe within three to four days of treatment with pHENOMMenal probiotic, and
blood phe concentrations remained significantly reduced (P < 0.0005) compared to
untreated controls during the course of experiments. Although pHENOMMenal
probiotic could be cultured from fecal samples at four months post treatment, it
could no longer be cultivated from feces at eight months post treatment,
indicating eventual loss of the microbe from the gut. Preliminary screens during
experimentation found no immune response to AvPAL. Collectively these studies
provide data for the use of a genetically engineered probiotic as a potential
treatment for PKU.
PMID- 28520730
TI - Analysis of heterogeneity in T2-weighted MR images can differentiate
pseudoprogression from progression in glioblastoma.
AB - PURPOSE: To develop an image analysis technique that distinguishes
pseudoprogression from true progression by analyzing tumour heterogeneity in T2
weighted images using topological descriptors of image heterogeneity called
Minkowski functionals (MFs). METHODS: Using a retrospective patient cohort (n =
50), and blinded to treatment response outcome, unsupervised feature estimation
was performed to investigate MFs for the presence of outliers, potential
confounders, and sensitivity to treatment response. The progression and
pseudoprogression groups were then unblinded and supervised feature selection was
performed using MFs, size and signal intensity features. A support vector machine
model was obtained and evaluated using a prospective test cohort. RESULTS: The
model gave a classification accuracy, using a combination of MFs and size
features, of more than 85% in both retrospective and prospective datasets. A
different feature selection method (Random Forest) and classifier (Lasso) gave
the same results. Although not apparent to the reporting radiologist, the T2
weighted hyperintensity phenotype of those patients with progression was
heterogeneous, large and frond-like when compared to those with
pseudoprogression. CONCLUSION: Analysis of heterogeneity, in T2-weighted MR
images, which are acquired routinely in the clinic, has the potential to detect
an earlier treatment response allowing an early change in treatment strategy.
Prospective validation of this technique in larger datasets is required.
PMID- 28520732
TI - Differential gene expression along the animal-vegetal axis in the ascidian embryo
is maintained by a dual functional protein Foxd.
AB - In many animal embryos, a specific gene expression pattern is established along
the animal-vegetal axis soon after zygotic transcription begins. In the embryo of
the ascidian Ciona intestinalis, soon after the division that separates animal
and vegetal hemispheres into distinct blastomeres, maternal Gata.a and beta
catenin activate specific genes in the animal and vegetal blastomeres,
respectively. On the basis of these initial distinct gene expression patterns,
gene regulatory networks promote animal cells to become ectodermal tissues and
vegetal cells to become endomesodermal tissues and a part of the nerve cord. In
the vegetal hemisphere, beta-catenin directly activates Foxd, an essential
transcription factor gene for specifying endomesodermal fates. In the present
study, we found that Foxd also represses the expression of genes that are
activated specifically in the animal hemisphere, including Dmrt1, Prdm1-r.a
(Bz1), Prdm1-r.b (Bz2), and Otx. A reporter assay showed that Dmrt1 expression
was directly repressed by Foxd, and a chromatin immunoprecipitation assay showed
that Foxd was bound to the upstream regions of Dmrt1, Prdm1-r.a, Prdm1-r.b, and
Otx. Thus, Foxd has a dual function of activating specific gene expression in the
vegetal hemisphere and of repressing the expression of genes that are normally
expressed in the animal hemisphere. This dual function stabilizes the initial
patterning along the animal-vegetal axis by beta-catenin and Gata.a.
PMID- 28520733
TI - Environmental DNA method for estimating salamander distribution in headwater
streams, and a comparison of water sampling methods.
AB - Environmental DNA (eDNA) has recently been used for detecting the distribution of
macroorganisms in various aquatic habitats. In this study, we applied an eDNA
method to estimate the distribution of the Japanese clawed salamander,
Onychodactylus japonicus, in headwater streams. Additionally, we compared the
detection of eDNA and hand-capturing methods used for determining the
distribution of O. japonicus. For eDNA detection, we designed a qPCR primer/probe
set for O. japonicus using the 12S rRNA region. We detected the eDNA of O.
japonicus at all sites (with the exception of one), where we also observed them
by hand-capturing. Additionally, we detected eDNA at two sites where we were
unable to observe individuals using the hand-capturing method. Moreover, we found
that eDNA concentrations and detection rates of the two water sampling areas
(stream surface and under stones) were not significantly different, although the
eDNA concentration in the water under stones was more varied than that on the
surface. We, therefore, conclude that eDNA methods could be used to determine the
distribution of macroorganisms inhabiting headwater systems by using samples
collected from the surface of the water.
PMID- 28520734
TI - Interfacial mechanisms for stability of surfactant-laden films.
AB - Thin liquid films are central to everyday life. They are ubiquitous in modern
technology (pharmaceuticals, coatings), consumer products (foams, emulsions) and
also serve vital biological functions (tear film of the eye, pulmonary
surfactants in the lung). A common feature in all these examples is the presence
of surface-active molecules at the air-liquid interface. Though they form only
molecular-thin layers, these surfactants produce complex surface stresses on the
free surface, which have important consequences for the dynamics and stability of
the underlying thin liquid film. Here we conduct simple thinning experiments to
explore the fundamental mechanisms that allow the surfactant molecules to slow
the gravity-driven drainage of the underlying film. We present a simple model
that works for both soluble and insoluble surfactant systems in the limit of
negligible adsorption-desorption dynamics. We show that surfactants with finite
surface rheology influence bulk flow through viscoelastic interfacial stresses,
while surfactants with inviscid surfaces achieve stability through opposing
surface-tension induced Marangoni flows.
PMID- 28520735
TI - Pain in methadone patients: Time to address undertreatment and suicide risk (ANRS
Methaville trial).
AB - BACKGROUND: Pain in opioid-dependent patients is common but data measuring the
course of pain (and its correlates) using validated scales in patients initiating
methadone treatment are sparse. We aimed to assess pain and its interference in
daily life, associated correlates, and undertreatment before and during methadone
treatment. METHODS: This is a secondary analysis using longitudinal data of a
randomized trial comparing two methadone initiation models. We assessed the
effect of methadone initiation and other correlates on pain intensity and
interference (using the Brief Pain Inventory) at months 0, 6 and 12 using a mixed
multinomial logistic regression model. RESULTS: The study group comprised 168
patients who had data for either pain intensity or interference for at least one
visit. Moderate to severe pain was reported in 12.9% of patients at M0, 5.4% at
M6 and 7.3% at M12. Substantial interference with daily functioning was reported
in 36.0% at M0, 14.5% at M6 and 17.1% at M12. Of the 98 visits where patients
reported moderate to severe pain or substantial interference, 55.1% reported no
treatment for pain relief, non-opioid analgesics were reported by 34.7%, opioid
analgesics by 3.1% and both opioid and non-opioid analgesics by 7.1%. Methadone
was associated with decreased pain intensity at 6 months (OR = 0.29, p = 0.04)
and 12 months (OR = 0.30, p = 0.05) of follow-up and tended to be associated with
substantial pain interference. Suicide risk was associated with both pain
intensity and pain interference. CONCLUSIONS: Methadone in opioid-dependent
patients can reduce pain. However, undertreatment of pain in methadone patients
remains a major clinical concern. Patients with pain are at higher risk of
suicide. Adequate screening and management of pain in this population is a
priority and needs to be integrated into routine comprehensive care.
PMID- 28520736
TI - The bantam microRNA acts through Numb to exert cell growth control and feedback
regulation of Notch in tumor-forming stem cells in the Drosophila brain.
AB - Notch (N) signaling is central to the self-renewal of neural stem cells (NSCs)
and other tissue stem cells. Its deregulation compromises tissue homeostasis and
contributes to tumorigenesis and other diseases. How N regulates stem cell
behavior in health and disease is not well understood. Here we show that N
regulates bantam (ban) microRNA to impact cell growth, a process key to NSC
maintenance and particularly relied upon by tumor-forming cancer stem cells.
Notch signaling directly regulates ban expression at the transcriptional level,
and ban in turn feedback regulates N activity through negative regulation of the
Notch inhibitor Numb. This feedback regulatory mechanism helps maintain the
robustness of N signaling activity and NSC fate. Moreover, we show that a Numb
Myc axis mediates the effects of ban on nucleolar and cellular growth
independently or downstream of N. Our results highlight intricate transcriptional
as well as translational control mechanisms and feedback regulation in the N
signaling network, with important implications for NSC biology and cancer
biology.
PMID- 28520737
TI - Outdoor spatial spraying against dengue: A false sense of security among
inhabitants of Hermosillo, Mexico.
AB - BACKGROUND: Government-administered adulticiding is frequently conducted in
response to dengue transmission worldwide. Anecdotal evidence suggests that
spraying may create a "false sense of security" for residents. Our objective was
to determine if there was an association between residents' reporting outdoor
spatial insecticide spraying as way to prevent dengue transmission and both their
reported frequency of dengue prevention practices and household entomological
indices in Hermosillo, Mexico. METHODOLOGY/PRINCIPAL FINDINGS: A non
probabilistic survey of 400 households was conducted in August 2014. An oral
questionnaire was administered to an adult resident and the outer premises of the
home were inspected for water-holding containers and presence of Ae. aegypti
larvae and pupae. Self-reported frequency of prevention practices were assessed
among residents who reported outdoor spatial spraying as a strategy to prevent
dengue (n = 93) and those who did not (n = 307). Mixed effects negative binomial
regression was used to assess associations between resident's reporting spraying
as a means to prevent dengue and container indices. Mixed effects logistic
regression was used to determine associations with presence/absence of larvae and
pupae. Those reporting spatial spraying disposed of trash less frequently and
spent less time indoors to avoid mosquitoes. They also used insecticides and
larvicides more often and covered their water containers more frequently. Their
backyards had more containers positive for Ae. aegypti (RR = 1.92) and there was
a higher probability of finding one or more Ae. aegypti pupae (OR = 2.20). Survey
respondents that reported spatial spraying prevented dengue were more likely to
be older and were exposed to fewer media sources regarding prevention.
CONCLUSIONS/SIGNIFICANCE: The results suggest that the perception that outdoor
spatial spraying prevents dengue is associated with lower adoption of prevention
practices and higher entomological risk. This provides some support to the
hypothesis that spraying may lead to a "false sense of security". Further
investigations to clarify this relationship should be conducted. Government
campaigns should emphasize the difficulty in controlling Ae. aegypti mosquitoes
and the need for both government and community action to minimize risk of dengue
transmission.
PMID- 28520738
TI - Pediatric fluoroquinolone prescription in South Korea before and after a
regulatory intervention: A nationwide study, 2007-2015.
AB - OBJECTIVE: To investigate the impact of national implementation of age
restriction on fluoroquinolone prescription in children and adolescents. METHODS:
Data collected from the database of Health Insurance Review and Assessment
Service in South Korea, a national health insurance system to analyze
fluoroquinolone prescribing practice in children and adolescents younger than 18
years, between 2007 and 2015. The age restriction was implemented in December
2009. The annual prescription rate of FQ per 100,000 person-years was calculated
and an autoregressive model was used to predict the prescription pattern if an
intervention had not occurred. RESULTS: A total of 505,859 children received
systemic fluoroquinolone during the study period-297,054 ciprofloxacin, and
208,805 levofloxacin. After implementation of the drug utilization review
program, the annual prescription rate for ciprofloxacin declined by 97.5% (from
840 to 21 per 100,000 person-years, P < 0.001), and for levofloxacin by 96.4%
(from 598 to 11 per 100,000 person-years, P < 0.001). The decline was more
dramatic in the outpatient setting than in the inpatient setting for both drugs.
CONCLUSION: The dramatic and sustained decline in prescription number and change
in prescription pattern after the regulatory action suggests that the
implementation under drug utilization review program was successful in
controlling excessive and inappropriate use of fluoroquinolones in children,
possibly guiding towards more judicious and selective prescription behavior.
PMID- 28520740
TI - Ascertaining the impact of catastrophic events on dengue outbreak: The 2014 gas
explosions in Kaohsiung, Taiwan.
AB - Infectious disease outbreaks often occur in the aftermath of catastrophic events,
either natural or man-made. While natural disasters such as typhoons/hurricanes,
flooding and earthquakes have been known to increase the risk of infectious
disease outbreak, the impact of anthropogenic disasters is less well-understood.
Kaohsiung City is located in southern Taiwan, where most dengue outbreaks had
occurred in the past two decades. It is also the center of petrochemical industry
in Taiwan with pipelines running underneath city streets. Multiple underground
gas explosions occurred in Kaohsiung in the evening of July 31, 2014 due to
chemical leaks in the pipelines. The explosions caused 32 deaths, including five
firefighters and two volunteer firefighters, and injured 321 persons.
Historically, dengue outbreaks in southern Taiwan occurred mostly in small
numbers of around 2000 cases or less, except in 2002 with over 5000 cases.
However, in the months after the gas explosions, the city reported 14528 lab
confirmed dengue cases from August to December. To investigate the possible
impact, if any, of the gas explosions on this record-breaking dengue outbreak, a
simple mathematical model, the Richards model, is utilized to study the temporal
patterns of the spread of dengue in the districts of Kaohsiung in the proximity
of the explosion sites and to pinpoint the waves of infections that had occurred
in each district in the aftermath of the gas explosions. The reproduction number
of each wave in each district is also computed. In the aftermath of the gas
explosions, early waves occurred 4-5 days (which coincides with the minimum of
human intrinsic incubation period for dengue) later in districts with multiple
waves. The gas explosions likely impacted the timing of the waves, but their
impact on the magnitude of the 2014 outbreak remains unclear. The modeling
suggests the need for public health surveillance and preparedness in the
aftermath of future disasters.
PMID- 28520739
TI - Timing-dependent LTP and LTD in mouse primary visual cortex following different
visual deprivation models.
AB - Visual deprivation during the critical period induces long-lasting changes in
cortical circuitry by adaptively modifying neuro-transmission and synaptic
connectivity at synapses. Spike timing-dependent plasticity (STDP) is considered
a strong candidate for experience-dependent changes. However, the visual
deprivation forms that affect timing-dependent long-term potentiation(LTP) and
long-term depression(LTD) remain unclear. Here, we demonstrated the temporal
window changes of tLTP and tLTD, elicited by coincidental pre- and post-synaptic
firing, following different modes of 6-day visual deprivation. Markedly broader
temporal windows were found in robust tLTP and tLTD in the V1M of the deprived
visual cortex in mice after 6-day MD and DE. The underlying mechanism for the
changes seen with visual deprivation in juvenile mice using 6 days of dark
exposure or monocular lid suture involves an increased fraction of NR2b
containing NMDAR and the consequent prolongation of NMDAR-mediated response
duration. Moreover, a decrease in NR2A protein expression at the synapse is
attributable to the reduction of the NR2A/2B ratio in the deprived cortex.
PMID- 28520741
TI - Highly regulated growth and development of the Ediacara macrofossil Dickinsonia
costata.
AB - The Ediacara Biota represents the oldest fossil evidence for the appearance of
animals but linking these taxa to specific clades has proved challenging.
Dickinsonia is an abundant, apparently bilaterally symmetrical Ediacara fossil
with uncertain affinities. We identified and measured key morphological features
of over 900 specimens of Dickinsonia costata from the Ediacara Member, South
Australia to characterize patterns in growth and morphology. Here we show that
development in Dickinsonia costata was surprisingly highly regulated to maintain
an ovoid shape via terminal addition and the predictable expansion of modules.
This result, along with other characters found in Dickinsonia suggests that it
does not belong within known animal groups, but that it utilized some of the
developmental gene networks of bilaterians, a result predicted by gene sequencing
of basal metazoans but previously unidentified in the fossil record. Dickinsonia
thus represents an extinct clade located between sponges and the last common
ancestor of Protostomes and Deuterostomes, and likely belongs within the
Eumetazoa.
PMID- 28520742
TI - Experimental outgassing of toxic chemicals to simulate the characteristics of
hazards tainting globally shipped products.
AB - Ambient monitoring analyses may identify potential new public health hazards such
as residual levels of fumigants and industrial chemicals off gassing from
products and goods shipped globally. We analyzed container air with gas
chromatography coupled to mass spectrometry (TD-2D-GC-MS/FPD) and assessed
whether the concentration of the volatiles benzene and 1,2-dichloroethane
exceeded recommended exposure limits (REL). Products were taken from transport
containers and analyzed for outgassing of volatiles. Furthermore, experimental
outgassing was performed on packaging materials and textiles, to simulate the
hazards tainting from globally shipped goods. The mean amounts of benzene in
analyzed container air were 698-fold higher, and those of ethylene dichloride
were 4.5-fold higher than the corresponding REL. More than 90% of all containers
struck with toluene residues higher than its REL. For 1,2-dichloroethane 53% of
containers, transporting shoes exceeded the REL. In standardized experimental
fumigation of various products, outgassing of 1,2-dichloroethane under controlled
laboratory conditions took up to several months. Globally produced transported
products tainted with toxic industrial chemicals may contribute to the mixture of
volatiles in indoor air as they are likely to emit for a long period. These
results need to be taken into account for further evaluation of safety standards
applying to workers and consumers.
PMID- 28520744
TI - Indoor simulations reveal differences among plant species in capturing
particulate matter.
AB - A number of studies have focused on the capacity of urban trees and shrubs to
serve as efficient biological filters to mitigate air pollution. In this study,
five different tree species were assessed for this function. Kerria japonica,
Sophora japonica, Philadelphus pekinensis, Gleditsia sinensis, and Prunus persica
'Atropurpurea' were tested in a deposition chamber using (NH4)2SO4 particles. We
quantified and compared the capability of all tested trees to remove particles by
assessing deposition velocity, a measure of the ability to remove particles. When
placed in the deposition chamber, S. japonica had the greatest deposition
velocity, followed by Philadelphus pekinensis, G. sinensis, Prunus persica
'Atropurpurea,' and K. japonica, in descending order. In addition, the comparison
of deposition velocities among these species suggested that certain leaf
geometries and surface characteristics of broadleaf trees, such as trichomes and
grooves, increased particle capture. However, these results change under a
different simulation condition using ambient air, suggesting that some trees
actually increase pollutant number concentrations more than reduce particle
concentration. This outcome can be explained by the aerodynamic effect of trees
exceeding the filtering capacity of vegetation under some conditions. This
highlights the difficulty of generalizing species selection criteria for practice
use. Accordingly, our results indicate that using vegetation to reduce particle
pollution and improve the air quality is not a universally advisable and viable
solution.
PMID- 28520743
TI - Whole brain volume changes and its correlation with clinical symptom severity in
patients with schizophrenia: A DARTEL-based VBM study.
AB - The purpose of this study was to evaluate gray matter (GM) and white matter (WM)
volume alterations in whole-brain structures in patients with schizophrenia and
healthy controls using voxel-based morphometry (VBM), and further to assess the
correlation between GM and WM volume variations and symptom severity in
schizophrenia. A total of 22 patients with schizophrenia and 22 age-matched
healthy controls participated. Magnetic resonance image data were processed using
SPM8 software with diffeomorphic anatomical registration via an exponentiated Lie
algebra (DARTEL) algorithm. Patients with schizophrenia exhibited significantly
decreased GM volumes of the insula, superior temporal gyrus (STG), gyrus rectus,
and anterior cingulate cortex (ACC) compared with healthy controls. The GM
volumes of the STG and gyrus rectus were negatively correlated with the positive
scales on the Positive and Negative Syndrome Scale (PANSS) and those of the STG
and ACC were negatively correlated with the negative scales. The durations of
illness in schizophrenia were negatively correlated with the GM volumes of the
insula, STG, and ACC. Patients with schizophrenia exhibited significantly
decreased WM volumes of the superior frontal gyrus, inferior temporal gyrus, and
STG. The WM volumes of the STG were negatively correlated with the duration of
illness. Our findings suggest that GM and WM volume abnormalities in the STG are
associated with the psychopathology of schizophrenia.
PMID- 28520745
TI - High handaxe symmetry at the beginning of the European Acheulian: The data from
la Noira (France) in context.
AB - In the last few decades, new discoveries have pushed the beginning of the biface
rich European Acheulian from 500 thousand years (ka) ago back to at least 700 ka,
and possibly to 1 million years (Ma) ago. It remains, however, unclear to date if
handaxes arrived in Europe as a fully developed technology or if they evolved
locally from core-and-flake industries. This issue is also linked with another
long-standing debate on the existence and behavioral, cognitive, and social
meaning of a possibly chronological trend for increased handaxe symmetry
throughout the Lower Paleolithic. The newly discovered sites can provide a link
between the much older Acheulian in Africa and the Levant and the well-known
assemblages from the later European Acheulian, enabling a rigorous testing of
these hypotheses using modern morphometric methods. Here we use the Continuous
Symmetry Measure (CSM) method to quantify handaxe symmetry at la Noira, a newly
excavated site in central France, which features two archaeological levels,
respectively ca. 700 ka and 500 ka old. In order to provide a context for the new
data, we use a large aggregate from the well-known 500 ka old site of Boxgrove,
England. We show that handaxes from the oldest layer at la Noira, although on
average less symmetric than both those from the younger layers at the same site
and than those from Boxgrove, are nevertheless much more symmetric than other
early Acheulian specimens evaluated using the CSM method. We also correlate
trends in symmetry to degree of reduction, demonstrating that raw material
availability and discard patterns may affect observed symmetry values. We
conclude that it is likely that, by the time the Acheulian arrived in Europe, its
makers were, from a cognitive and motor-control point of view, already capable of
producing the symmetric variant of this technology.
PMID- 28520747
TI - An index-based algorithm for fast on-line query processing of latent semantic
analysis.
AB - Latent Semantic Analysis (LSA) is widely used for finding the documents whose
semantic is similar to the query of keywords. Although LSA yield promising
similar results, the existing LSA algorithms involve lots of unnecessary
operations in similarity computation and candidate check during on-line query
processing, which is expensive in terms of time cost and cannot efficiently
response the query request especially when the dataset becomes large. In this
paper, we study the efficiency problem of on-line query processing for LSA
towards efficiently searching the similar documents to a given query. We rewrite
the similarity equation of LSA combined with an intermediate value called partial
similarity that is stored in a designed index called partial index. For reducing
the searching space, we give an approximate form of similarity equation, and then
develop an efficient algorithm for building partial index, which skips the
partial similarities lower than a given threshold theta. Based on partial index,
we develop an efficient algorithm called ILSA for supporting fast on-line query
processing. The given query is transformed into a pseudo document vector, and the
similarities between query and candidate documents are computed by accumulating
the partial similarities obtained from the index nodes corresponds to non-zero
entries in the pseudo document vector. Compared to the LSA algorithm, ILSA
reduces the time cost of on-line query processing by pruning the candidate
documents that are not promising and skipping the operations that make little
contribution to similarity scores. Extensive experiments through comparison with
LSA have been done, which demonstrate the efficiency and effectiveness of our
proposed algorithm.
PMID- 28520746
TI - DNA recognition by an RNA-guided bacterial Argonaute.
AB - Argonaute (Ago) proteins are widespread in prokaryotes and eukaryotes and share a
four-domain architecture capable of RNA- or DNA-guided nucleic acid recognition.
Previous studies identified a prokaryotic Argonaute protein from the eubacterium
Marinitoga piezophila (MpAgo), which binds preferentially to 5'-hydroxylated
guide RNAs and cleaves single-stranded RNA (ssRNA) and DNA (ssDNA) targets. Here
we present a 3.2 A resolution crystal structure of MpAgo bound to a 21-nucleotide
RNA guide and a complementary 21-nucleotide ssDNA substrate. Comparison of this
ternary complex to other target-bound Argonaute structures reveals a unique
orientation of the N-terminal domain, resulting in a straight helical axis of the
entire RNA-DNA heteroduplex through the central cleft of the protein.
Additionally, mismatches introduced into the heteroduplex reduce MpAgo cleavage
efficiency with a symmetric profile centered around the middle of the helix. This
pattern differs from the canonical mismatch tolerance of other Argonautes, which
display decreased cleavage efficiency for substrates bearing sequence mismatches
to the 5' region of the guide strand. This structural analysis of MpAgo bound to
a hybrid helix advances our understanding of the diversity of target recognition
mechanisms by Argonaute proteins.
PMID- 28520748
TI - Inflammation-related microRNA expression level in the bovine milk is affected by
mastitis.
AB - MicroRNA (miRNA) in tissue and liquid samples have been shown to be associated
with many diseases including inflammation. We aimed to identify inflammation
related miRNA expression level in the bovine mastitis milk. Expression level of
inflammation-related miRNA in milk from mastitis-affected and normal cows was
analyzed using qPCR. We found that expression level of miR-21, miR-146a, miR-155,
miR-222, and miR-383 was significantly upregulated in California mastitis test
positive (CMT+) milk. We further analyzed these miRNA using a chip-based
QuantStudio Digital PCR System. The digital PCR results correlated with those of
qPCR, demonstrating upregulation of miR-21, miR-146a, miR-155, miR-222, and miR
383 in CMT+ milk. In conclusion, we identified miRNA that are upregulated in CMT+
milk. These miRNA exhibited sensitivity and specificity greater than 80% for
differentiating between CMT+ milk and normal milk. Our findings suggest that
inflammation-related miRNA expression level in the bovine milk was affected by
mastitis, and miRNA in milk have potential for use as biomarkers of bovine
mastitis.
PMID- 28520749
TI - Access and response to direct antiviral agents (DAA) in HIV-HCV co-infected
patients in Italy: Data from the Icona cohort.
AB - BACKGROUND: Real-life data on access and response to direct antiviral agents
(DAA) in HIV-HCV coinfected individuals are lacking. METHODS: HCV viremic, HIV
positive patients from Icona and Hepaicona cohorts naive to DAA by January 2013
were included. Access and predictors of starting DAA were evaluated. Switches of
antiretroviral drugs at starting DAA were described. We calculated sustained
virological response (SVR12) in those reaching 12 weeks after end-of-treatment
(EOT), and defined treatment failure (TF) as discontinuation of DAA before EOT or
non-SVR12. Statistical analyses included Kaplan-Meier curves, univariable and
multivariable analyses evaluating predictors of access to DAA and of treatment
outcome (non-SVR and TF). RESULTS: 2,607 patients included. During a median
follow-up of 38 (IQR:30-41) months, 920 (35.3%) patients started DAA. Eligibility
for reimbursement was the strongest predictor to access to treatment: 761/1,090
(69.8%) eligible and 159/1,517 (10.5%) non-eligible to DAA reimbursement. Older
age, HIV-RNA<=50 copies/mL were associated to faster DAA initiation, higher CD4
count and HCV-genotype 3 with delayed DAA initiation in those eligible to DAA
reimbursement. Up to 28% of patients (36% of those on ritonavir-boosted protease
inhibitors, PI/r) underwent antiretroviral (ART) modification at DAA initiation.
545/595 (91.6%) patients reaching EOT achieved SVR12. Overall, TF occurred in
61/606 patients (10.1%), with 11 discontinuing DAA before EOT. Suboptimal DAA was
the only independent predictor of both non-SVR12 (AHR 2.52, 95%CI:1.24-5.12) and
TF (AHR: 2.19; 95%CI:1.13-4.22). CONCLUSIONS: Only 35.3% had access to HCV
treatment. Despite excellent rates of SVR12 rates (91.6%), only 21% (545/2,607)
of our HIV-HCV co-infected patients are cured.
PMID- 28520750
TI - Awareness and trust of the FDA and CDC: Results from a national sample of US
adults and adolescents.
AB - Trust in government agencies plays a key role in advancing these organizations'
agendas, influencing behaviors, and effectively implementing policies. However,
few studies have examined the extent to which individuals are aware of and trust
the leading United States agencies devoted to protecting the public's health.
Using two national samples of adolescents (N = 1,125) and adults (N = 5,014), we
examined demographic factors, with a focus on vulnerable groups, as correlates of
awareness of and trust in the Centers for Disease Control and Prevention (CDC),
Food and Drug Administration (FDA), and the federal government. From nine
different weighted and adjusted logistic regression models, we found high levels
of awareness of the existence of the FDA and CDC (ranging from 55.7% for
adolescents' awareness of the CDC to 94.3% for adults' awareness of the FDA) and
moderate levels of trust (ranging from a low of 41.8% for adults' trust in the
federal government and a high of 78.8% for adolescents' trust of the FDA). In the
adolescent and adult samples, awareness was higher among non-Hispanic Blacks and
respondents with low numeracy. With respect to trust, few consistent demographic
differences emerged. Our findings provide novel insights regarding awareness and
trust in the federal government and specific United States public health
agencies. Our findings suggest groups to whom these agencies may want to
selectively communicate to enhance trust and thus facilitate their communication
and regulatory agendas.
PMID- 28520751
TI - "Do it-yourself": Home blood pressure as a predictor of traditional and everyday
cognition in older adults.
AB - BACKGROUND: Hypertension guidelines recommend home blood pressure (HBP)
monitoring in adjunct to office blood pressure (OBP) for its greater
reproducibility and prognostic utility in the prevention of cardiovascular
outcomes, especially stroke. To date, the relationship between HBP and cognitive
function remains unexplored. METHODS: We examined HBP as a cognitive predictor in
a multi-ethnic group of community-dwelling adults aged 60 and over (N = 133)
using neuropsychological measures and analyzed the data using multiple regression
analyses. We also employed "everyday cognition" measures that have been found to
have higher prognostic utility for real-world functioning than traditional
cognitive tasks. RESULTS: Good to perfect HBP monitoring compliance over seven
days was achieved by 88.7% of the participants with superior reliability
(ICC>=.96) to office readings. Higher home systolic BP and pulse pressure
predicted worse processing speed, executive function, and everyday cognitive
function, whereas lower home diastolic BP predicted worse everyday cognition.
Office readings were similarly associated with everyday cognitive function but
with no other cognitive measures. CONCLUSION: Our findings are the first to
validate HBP as a predictor of neuropsychological function in older adults beyond
cognitive screening. Differential relationships among blood pressure variables
and specific cognitive domains were observed. With proper standardization and
training, we demonstrated that HBP can be obtained in a multi-ethnic community
dwelling older adult cohort. Our findings emphasize the importance of employing
blood pressure and cognitive measures that are adequately sensitive to detect
vascular-related cognitive impairment in a relatively healthy population.
Implications regarding proper HBP measurement for hypertension management,
cognitive health, and everyday function are discussed.
PMID- 28520752
TI - Antimicrobial peptides extend lifespan in Drosophila.
AB - Antimicrobial peptides (AMPs) are important defense molecules of the innate
immune system. High levels of AMPs are induced in response to infections to fight
pathogens, whereas moderate levels induced by metabolic stress are thought to
shape commensal microbial communities at barrier tissues. We expressed single
AMPs in adult flies either ubiquitously or in the gut by using the inducible
GeneSwitch system to tightly regulate AMP expression. We found that activation of
single AMPs, including Drosocin, resulted in a significant extension of
Drosophila lifespan. These animals showed reduced activity of immune pathways
over lifetime, less intestinal regenerative processes, reduced stress response
and a delayed loss of gut barrier integrity. Furthermore, intestinal Drosocin
induction protected the animals against infections with the natural Drosophila
pathogen Pseudomonas entomophila, whereas a germ-reduced environment prevented
the lifespan extending effect of Drosocin. Our study provides new insights into
the crosstalk of innate immunity, intestinal homeostasis and ageing.
PMID- 28520753
TI - Comparative accuracy of CT perfusion in diagnosing acute ischemic stroke: A
systematic review of 27 trials.
AB - OBJECTIVE: To systematically evaluate and compare the diagnostic accuracy of CT
perfusion (CTP), non-enhanced computed tomography (NCCT) and computed tomography
angiography (CTA) in detecting acute ischemic stroke. METHODS: We searched seven
databases and screened the reference lists of the included studies. The risk of
bias in the study quality was assessed using QUADASII. We produced paired forest
plots in RevMan to show the variation of the sensitivity and specificity
estimates together with their 95% CI. We used a hierarchical summary ROC model to
summarize the sensitivity and specificity of CTP in detecting ischemic stroke.
RESULTS: We identified 27 studies with a total of 2168 patients. The pooled
sensitivity of CTP for acute ischemic stroke was 82% (95% CI 75-88%), and the
specificity was 96% (95% CI 89-99%). CTP was more sensitive than NCCT and had a
similar accuracy with CTA. There were no statistically significant differences in
the sensitivity and specificity between patients who underwent CTP within 6 hours
of symptom onset and beyond 6 hours after symptom onset. No adverse events were
reported in the included studies. CONCLUSIONS: CTP is more accurate than NCCT and
has similar accuracy to CTA in detecting acute ischemic stroke. However, the
evidence is not strong. There is potential benefit of using CTP to select stroke
patients for treatment, but more high-quality evidence is needed to confirm this
result.
PMID- 28520754
TI - Effects of milk product intake on thigh muscle strength and NFKB gene methylation
during home-based interval walking training in older women: A randomized,
controlled pilot study.
AB - BACKGROUND: Muscle atrophy with aging is closely associated with chronic systemic
inflammation and lifestyle-related diseases. In the present study, we assessed
whether post-exercise milk product intake during 5-month interval walking
training (IWT) enhanced the increase in thigh muscle strength and ameliorated
susceptibility to inflammation in older women. METHODS: Subjects [n = 37, 66+/-5
(standard deviation) yrs] who had been performing IWT for >6 months participated
in this study. They were randomly divided into the following 3 groups: IWT alone
(CNT, n = 12), IWT + low-dose post-exercise milk product intake (LD, n = 12; 4 g
protein and 3 g carbohydrate) or IWT + a 3-times higher dose of milk product
intake than the LD group (HD, n = 13). They were instructed to repeat >=5 sets of
fast and slow walking for 3 min each at >=70% and 40% peak aerobic capacity for
walking, respectively, per day for >=4 days/week. RESULTS: After IWT, thigh
muscle strength increased in the HD group (8+/-2%) more than in the CNT group (
2+/-3%, P = 0.022), despite similar IWT achievements between the groups (P>0.15).
Pyrosequencing analysis using whole blood showed that methylation of NFKB1 and
NFKB2, master genes of inflammation, was enhanced in the HD group (29+/-7% and
44+/-11%, respectively) more than in the CNT group (-20+/-6% and -10+/-6%,
respectively; P<0.001). Moreover, the genome-wide DNA methylation analysis showed
that several inflammation-related genes were hyper-methylated in the HD group
compared with that in the CNT group, suggesting greater pro-inflammatory cytokine
gene suppression in the HD group. CONCLUSION: HD milk product intake after
exercise produced a greater percent increase in thigh muscle strength and NFKB1
and NFKB2 gene methylation during IWT in physically active older women. TRIAL
REGISTRATION: UMIN-CTR No. UMIN000024544 and No. UMIN000024912.
PMID- 28520755
TI - Neuropsychological characteristics of Gulf War illness: A meta-analysis.
AB - OBJECTIVE: Gulf War illness (GWI) is a disorder related to military service in
the 1991 GW. Prominent symptoms include fatigue, pain and cognitive problems.
These symptoms were reported by GW Veterans (GWV) immediately after the war and
were eventually incorporated into case definitions of GWI. Neuropsychological
function in GW veterans has been studied both among deployed GWV and in GWV
diagnosed with GWI. Results have been inconsistent between and across GW
populations. The purpose of the present investigation was to better characterize
neuropsychological function in this veteran population. METHODS: Meta-analysis
techniques were applied to published studies on neuropsychological performance in
GWV to identify domains of dysfunction in deployed vs. non-deployed GW-era
veterans and symptomatic vs. non-symptomatic GWVs. RESULTS: Significantly
decreased performance was found in three functional domains: attention and
executive function, visuospatial skills and learning/memory. CONCLUSIONS: These
findings document the cognitive decrements associated with GW service, validate
current GWI case definitions using cognitive criteria, and identify test measures
for use in GWI research assessing GWI treatment trial efficacy.
PMID- 28520757
TI - Predicting above-ground density and distribution of small mammal prey species at
large spatial scales.
AB - Grassland and shrub-steppe ecosystems are increasingly threatened by
anthropogenic activities. Loss of native habitats may negatively impact important
small mammal prey species. Little information, however, is available on the
impact of habitat variability on density of small mammal prey species at broad
spatial scales. We examined the relationship between small mammal density and
remotely-sensed environmental covariates in shrub-steppe and grassland ecosystems
in Wyoming, USA. We sampled four sciurid and leporid species groups using line
transect methods, and used hierarchical distance-sampling to model density in
response to variation in vegetation, climate, topographic, and anthropogenic
variables, while accounting for variation in detection probability. We created
spatial predictions of each species' density and distribution. Sciurid and
leporid species exhibited mixed responses to vegetation, such that changes to
native habitat will likely affect prey species differently. Density of white
tailed prairie dogs (Cynomys leucurus), Wyoming ground squirrels (Urocitellus
elegans), and leporids correlated negatively with proportion of shrub or
sagebrush cover and positively with herbaceous cover or bare ground, whereas
least chipmunks showed a positive correlation with shrub cover and a negative
correlation with herbaceous cover. Spatial predictions from our models provide a
landscape-scale metric of above-ground prey density, which will facilitate the
development of conservation plans for these taxa and their predators at spatial
scales relevant to management.
PMID- 28520756
TI - De novo assembly and comparative transcriptome analysis of the foot from Chinese
green mussel (Perna viridis) in response to cadmium stimulation.
AB - The Chinese green mussel, Perna viridis, is a marine bivalve with important
economic values as well as biomonitoring roles for aquatic pollution. Byssus,
secreted by the foot gland, has been proved to bind heavy metals effectively. In
this study, using the RNA sequencing technology, we performed comparative
transcriptomic analysis on the mussel feet with or without inducing by cadmium
(Cd). Our current work is aiming at providing insights into the molecular
mechanisms of byssus binding to heavy metal ions. The transcriptome sequencing
generated a total of 26.13-Gb raw data. After a careful assembly of clean data,
we obtained a primary set of 105,127 unigenes, in which 32,268 unigenes were
annotated. Based on the expression profiles, we identified 9,048 differentially
expressed genes (DEGs) between Cd treatment (50 or 100 MUg/L) at 48 h and the
control, suggesting an extensive transcriptome response of the mussels during the
Cd stimulation. Moreover, we observed that the expression levels of 54 byssus
protein coding genes increased significantly after the 48-h Cd stimulation. In
addition, 16 critical byssus protein coding genes were picked for profiling by
quantitative real-time PCR (qRT-PCR). Finally, we reached a primary conclusion
that high content of tyrosine (Tyr), cysteine (Cys), histidine (His) residues or
the special motif plays an important role in the accumulation of heavy metals in
byssus. We also proposed an interesting model for the confirmed byssal Cd
accumulation, in which biosynthesis of byssus proteins may play simultaneously
critical roles since their transcription levels were significantly elevated.
PMID- 28520759
TI - First evidence of the Hepatitis E virus in environmental waters in Colombia.
AB - Hepatitis E virus (HEV) is one of the main causes of acute viral hepatitis of
enteric transmission. HEV has been detected in environmental samples in several
countries from Europe and Asia, constituting a risk factor for waterborne
infection. In Colombia, HEV has been identified in samples obtained from patients
as well as from swine, but no environmental studies have been carried out. To
determine if HEV is present in environmental waters, samples from the main source
of drinking water plant and of wastewater system of eight municipalities and two
villages of Antioquia state (North West Colombia), were collected between
December 2012 and April 2014. The HEV genome was detected by RT-PCR in 23.3%
(7/30) of the samples from the main source of drinking water plants and in 16.7%
(5/30) from sewage. Viral concentrates obtained from three positive sewage
samples were used to inoculate HepG2 cell cultures that were followed for one
month; however, the viral genome was not detected in any cell culture. This study
demonstrates the circulation of HEV in both source of drinking water plants and
wastewater in Antioquia state, Colombia. The presence of HEV in environmental
waters could be a risk for waterborne transmission in this population. The
findings of the present study, together with the evidence of HEV circulation in
human and swine in Colombia, should be consider by public health authorities for
the development of surveillance programs and the inclusion of HEV infection
diagnosis in the guidelines of viral hepatitis in the country. This is the first
report of HEV in environmental samples in Colombia and the second one in Latin
America.
PMID- 28520758
TI - Cumulative family risks across income levels predict deterioration of children's
general health during childhood and adolescence.
AB - Family is considered an important agent in the health development of children.
This process is significant but quite complex because the prevalence of potential
risk factors in the family can hinder children's health. This study examined if
multiple family risks might have cumulative effect on children and youth's health
across various levels of household income. The data in this study were drawn from
the 2011-2012 U.S. National Survey of Children's Health (N = 79,601). A
cumulative family risk (CFR) index was developed, which included such constructs
as single-parenthood, unstable employment, large family, parenting stress, poor
maternal education, poor maternal general health and poor maternal mental health.
Multiple logistic regression analyses showed that CFR level was significantly
related to children and youth's poor health outcome (p < .001). When poverty
levels were considered, however, the impact of CFRs on children and youth's
health was attenuated. The impact of CFRs was higher on children and youth from
affluent families than on those from poor families. Overall there was a
consistent pattern of trend in the point estimate as well as confidence limits as
levels of affluence and numbers of family risk increased although some of the
confidence intervals overlapped. Living in disadvantaged families might serve as
a protective factor against CFRs possibly through repeated exposure to hardships
and subsequent formation of resilience among some of the disadvantaged children.
PMID- 28520761
TI - Antibiotic use in South Korea from 2007 to 2014: A health insurance database
generated time series analysis.
AB - BACKGROUND: Inappropriate antibiotic use significantly contributes to antibiotic
resistance, resulting in reduced antibiotic efficacy and increasing physical
burden and cost of disease. The goal of this study was to explore antibiotic
usage patterns in South Korea using 2007-2014 health insurance claims data.
METHODS: We used the Health Insurance Review & Assessment Service data, which
represents nearly the entire population of South Korea, to discern patterns in
antibiotic prescribing practices. The daily dose, as defined by the World Health
Organization ([defined daily doses]/1000 inhabitants/day, [DID]), was used as a
measure of antibiotic use. Subgroup analyses were performed on the basis of
patient characteristics (sex, age, and disease) and provider characteristics
(type of medical institution). RESULTS: Antibiotic use in DID increased from 23.5
in 2007 to 27.7 in 2014. The <= 6 years old age group showed the highest level of
usage at 59.21 DID in 2014, and showed an increasing trend each year. DIDs of
beta-lactam antibacterials, penicillins (J01C), other beta-lactam antibacterials
(J01D), lincosamides and streptogramins (J01F), quinolone antibacterials (J01M),
and other antibacterials (J01X) increased over time. CONCLUSION: This study
provides valuable statistics regarding antibiotic usage in South Korea; this is
important for guiding health policy with regard to antibiotic usage. There is a
need for further study exploring antibiotics use and resistance.
PMID- 28520760
TI - Transcriptome profiling of ontogeny in the acridid grasshopper Chorthippus
biguttulus.
AB - Acridid grasshoppers (Orthoptera:Acrididae) are widely used model organisms for
developmental, evolutionary, and neurobiological research. Although there has
been recent influx of orthopteran transcriptomic resources, many use pooled
ontogenetic stages obscuring information about changes in gene expression during
development. Here we developed a de novo transcriptome spanning 7 stages in the
life cycle of the acridid grasshopper Chorthippus biguttulus. Samples from
different stages encompassing embryonic development through adults were used for
transcriptomic profiling, revealing patterns of differential gene expression that
highlight processes in the different life stages. These patterns were validated
with semi-quantitative RT-PCR. Embryonic development showed a strongly
differentiated expression pattern compared to all of the other stages and genes
upregulated in this stage were involved in signaling, cellular differentiation,
and organ development. Our study is one of the first to examine gene expression
during post-embryonic development in a hemimetabolous insect and we found that
only the fourth and fifth instars had clusters of genes upregulated during these
stages. These genes are involved in various processes ranging from synthesis of
biogenic amines to chitin binding. These observations indicate that post
embryonic ontogeny is not a continuous process and that some instars are
differentiated. Finally, genes upregulated in the imago were generally involved
in aging and immunity. Our study highlights the importance of looking at ontogeny
as a whole and indicates promising directions for future research in orthopteran
development.
PMID- 28520762
TI - Indexical and linguistic processing by 12-month-olds: Discrimination of speaker,
accent and vowel differences.
AB - Infants preferentially discriminate between speech tokens that cross native
category boundaries prior to acquiring a large receptive vocabulary, implying a
major role for unsupervised distributional learning strategies in phoneme
acquisition in the first year of life. Multiple sources of between-speaker
variability contribute to children's language input and thus complicate the
problem of distributional learning. Adults resolve this type of indexical
variability by adjusting their speech processing for individual speakers. For
infants to handle indexical variation in the same way, they must be sensitive to
both linguistic and indexical cues. To assess infants' sensitivity to and
relative weighting of indexical and linguistic cues, we familiarized 12-month-old
infants to tokens of a vowel produced by one speaker, and tested their listening
preference to trials containing a vowel category change produced by the same
speaker (linguistic information), and the same vowel category produced by another
speaker of the same or a different accent (indexical information). Infants
noticed linguistic and indexical differences, suggesting that both are salient in
infant speech processing. Future research should explore how infants weight these
cues in a distributional learning context that contains both phonetic and
indexical variation.
PMID- 28520763
TI - Genome-wide gene expression array identifies novel genes related to disease
severity and excessive daytime sleepiness in patients with obstructive sleep
apnea.
AB - We aimed to identify novel molecular associations between chronic intermittent
hypoxia with re-oxygenation and adverse consequences in obstructive sleep apnea
(OSA). We analyzed gene expression profiles of peripheral blood mononuclear cells
from 48 patients with sleep-disordered breathing stratified into four groups:
primary snoring (PS), moderate to severe OSA (MSO), very severe OSA (VSO), and
very severe OSA patients on long-term continuous positive airway pressure
treatment (VSOC). Comparisons of the microarray gene expression data identified
eight genes up-regulated with OSA and down-regulated with CPAP treatment, and
five genes down-regulated with OSA and up-regulated with CPAP treatment. Protein
expression levels of two genes related to endothelial tight junction (AMOT P130,
and PLEKHH3), and three genes related to anti-or pro-apoptosis (BIRC3, ADAR1
P150, and LGALS3) were all increased in the VSO group, while AMOT P130 was
further increased, and PLEKHH3, BIRC3, and ADAR1 P150 were all decreased in the
VSOC group. Subgroup analyses revealed that AMOT P130 protein expression was
increased in OSA patients with excessive daytime sleepiness, BIRC3 protein
expression was decreased in OSA patients with hypertension, and LGALS3 protein
expression was increased in OSA patients with chronic kidney disease. In vitro
short-term intermittent hypoxia with re-oxygenation experiment showed immediate
over-expression of ADAR1 P150. In conclusion, we identified a novel association
between AMOT/PLEKHH3/BIRC3/ADAR1/LGALS3 over-expressions and high severity index
in OSA patients. AMOT and GALIG may constitute an important determinant for the
development of hypersomnia and kidney injury, respectively, while BIRC3 may play
a protective role in the development of hypertension.
PMID- 28520764
TI - Rib biomechanical properties exhibit diagnostic potential for accurate ageing in
forensic investigations.
AB - Age estimation remains one of the most challenging tasks in forensic practice
when establishing a biological profile of unknown skeletonised remains.
Morphological methods based on developmental markers of bones can provide
accurate age estimates at a young age, but become highly unreliable for ages over
35 when all developmental markers disappear. This study explores the changes in
the biomechanical properties of bone tissue and matrix, which continue to change
with age even after skeletal maturity, and their potential value for age
estimation. As a proof of concept we investigated the relationship of 28
variables at the macroscopic and microscopic level in rib autopsy samples from 24
individuals. Stepwise regression analysis produced a number of equations one of
which with seven variables showed an R2 = 0.949; a mean residual error of 2.13
yrs +/-0.4 (SD) and a maximum residual error value of 2.88 yrs. For forensic
purposes, by using only bench top machines in tests which can be carried out
within 36 hrs, a set of just 3 variables produced an equation with an R2 = 0.902
a mean residual error of 3.38 yrs +/-2.6 (SD) and a maximum observed residual
error 9.26yrs. This method outstrips all existing age-at-death methods based on
ribs, thus providing a novel lab based accurate tool in the forensic
investigation of human remains. The present application is optimised for fresh
(uncompromised by taphonomic conditions) remains, but the potential of the
principle and method is vast once the trends of the biomechanical variables are
established for other environmental conditions and circumstances.
PMID- 28520765
TI - An integrative analysis of tissue-specific transcriptomic and metabolomic
responses to short-term dietary methionine restriction in mice.
AB - Dietary methionine restriction (MR) produces a coordinated series of
transcriptional responses in peripheral tissues that limit fat accretion, remodel
lipid metabolism in liver and adipose tissue, and improve overall insulin
sensitivity. Hepatic sensing of reduced methionine leads to induction and release
of fibroblast growth factor 21 (FGF21), which acts centrally to increase
sympathetic tone and activate thermogenesis in adipose tissue. FGF21 also has
direct effects in adipose to enhance glucose uptake and oxidation. However, an
understanding of how the liver senses and translates reduced dietary methionine
into these transcriptional programs remains elusive. A comprehensive systems
biology approach integrating transcriptomic and metabolomic readouts in MR
treated mice confirmed that three interconnected mechanisms (fatty acid transport
and oxidation, tricarboxylic acid cycle, and oxidative phosphorylation) were
activated in MR-treated inguinal adipose tissue. In contrast, the effects of MR
in liver involved up-regulation of anti-oxidant responses driven by the nuclear
factor, erythroid 2 like 2 transcription factor, NFE2L2. Metabolomic analysis
provided evidence for redox imbalance, stemming from large reductions in the
master anti-oxidant molecule glutathione coupled with disproportionate increases
in ophthalmate and its precursors, glutamate and 2-aminobutyrate. Thus, cysteine
and its downstream product, glutathione, emerge as key early hepatic signaling
molecules linking dietary MR to its metabolic phenotype.
PMID- 28520767
TI - MS26/CYP704B is required for anther and pollen wall development in bread wheat
(Triticum aestivum L.) and combining mutations in all three homeologs causes male
sterility.
AB - Development of anthers and pollen represents an important aspect of the life
cycle in flowering plants. Genes contributing to anther and pollen development
have been widely studied in many plant species. Ms26/CYP704B genes play an
important role in pollen development through biosynthesis of sporopollenin for
pollen exine formation. To investigate the role of Ms26/CYP704B genes in anther
and pollen development of bread wheat, mutations in the A-, B-, and D-homeologs
of the putative Ms26/CYP704B gene were analyzed. Single and double homozygous
mutants in any of the homeologs did not affect pollen development and male
fertility. Triple homozygous mutants resulted in completely male sterile plants
that were defective in pollen and anther development. Additionally, double
homozygous-single heterozygous mutants were also male sterile although with
varying levels of residual fertility. The fertility of these triple mutants was
dependent upon the homeolog contributing the wild-type allele. Two heterologous
Ms26/CYP704B genes, when transformed into a triple homozygous mutant background,
completely restored male fertility, whereas a single gene was unable to restore
fertility. Functional analysis of Ms26/CYP704B furthers the understanding of male
fertility genes which can be utilized for the development of novel hybrid seed
production systems in wheat.
PMID- 28520766
TI - Transcriptomic analysis of salt stress responsive genes in Rhazya stricta.
AB - Rhazya stricta is an evergreen shrub that is widely distributed across Western
and South Asia, and like many other members of the Apocynaceae produces
monoterpene indole alkaloids that have anti-cancer properties. This species is
adapted to very harsh desert conditions making it an excellent system for
studying tolerance to high temperatures and salinity. RNA-Seq analysis was
performed on R. stricta exposed to severe salt stress (500 mM NaCl) across four
time intervals (0, 2, 12 and 24 h) to examine mechanisms of salt tolerance. A
large number of transcripts including genes encoding tetrapyrroles and
pentatricopeptide repeat (PPR) proteins were regulated only after 12 h of stress
of seedlings grown in controlled greenhouse conditions. Mechanisms of salt
tolerance in R. stricta may involve the upregulation of genes encoding chaperone
protein Dnaj6, UDP-glucosyl transferase 85a2, protein transparent testa 12 and
respiratory burst oxidase homolog protein b. Many of the highly-expressed genes
act on protecting protein folding during salt stress and the production of
flavonoids, key secondary metabolites in stress tolerance. Other regulated genes
encode enzymes in the porphyrin and chlorophyll metabolic pathway with important
roles during plant growth, photosynthesis, hormone signaling and abiotic
responses. Heme biosynthesis in R. stricta leaves might add to the level of salt
stress tolerance by maintaining appropriate levels of photosynthesis and normal
plant growth as well as by the participation in reactive oxygen species (ROS)
production under stress. We speculate that the high expression levels of PPR
genes may be dependent on expression levels of their targeted editing genes.
Although the results of PPR gene family indicated regulation of a large number of
transcripts under salt stress, PPR actions were independent of the salt stress
because their RNA editing patterns were unchanged.
PMID- 28520768
TI - Mobile phone reminders and peer counseling improve adherence and treatment
outcomes of patients on ART in Malaysia: A randomized clinical trial.
AB - BACKGROUND: Adherence to treatment remains the cornerstone of long term viral
suppression and successful treatment outcomes among patients receiving
Antiretroviral Therapy (ART). OBJECTIVE(S): Evaluate the effectiveness of mobile
phone reminders and peer counseling in improving adherence and treatment outcomes
among HIV positive patients on ART in Malaysia. METHODS: A single-blind, parallel
group RCT conducted in Hospital Sungai Buloh, Malaysia in which 242 adult
Malaysian patients were randomized to intervention or control groups.
Intervention consisted of a reminder module delivered through SMS and telephone
call reminders by trained research assistants for 24 consecutive weeks (starting
from date of ART initiation), in addition to adherence counseling at every clinic
visit. The length of intended follow up for each patient was 6 months. Data on
adherence behavior of patients was collected using specialized, pre-validated
Adult AIDS Clinical Trial Group (AACTG) adherence questionnaires. Data on weight,
clinical symptoms, CD4 count and viral load tests were also collected. Data was
analyzed using SPSS version 22 and R software. Repeated measures ANOVA,
Friedman's ANOVA and Multivariate regression models were used to evaluate
efficacy of the intervention. RESULTS: The response rate after 6 months follow up
was 93%. There were no significant differences at baseline in gender, employment
status, income distribution and residential location of respondents between the
intervention and control group. After 6 months follow up, the mean adherence was
significantly higher in the intervention group (95.7; 95% CI: 94.39-96.97) as
compared to the control group (87.5; 95% CI: 86.14-88.81). The proportion of
respondents who had Good (>95%) adherence was significantly higher in the
intervention group (92.2%) compared to the control group (54.6%). A significantly
lower frequency in missed appointments (14.0% vs 35.5%) (p = 0.001), lower viral
load (p = 0.001), higher rise in CD4 count (p = 0.017), lower incidence of
tuberculosis (p = 0.001) and OIs (p = 0.001) at 6 months follow up, was observed
among patients in the intervention group. CONCLUSION: Mobile phone reminders (SMS
and telephone call reminders) and peer counseling are effective in improving
adherence and treatment outcomes among HIV positive patients on ART in Malaysia.
These findings may be of potential benefit for collaborative adherence planning
between patients and health care providers at ART commencement.
PMID- 28520769
TI - Optimal method for assessment of respiratory muscle strength in neuromuscular
disorders using sniff nasal inspiratory pressure (SNIP).
AB - BACKGROUND: The ability to accurately determine respiratory muscle strength is
vitally important in patients with neuromuscular disorders (NMD). Sniff nasal
inspiratory pressure (SNIP), a test of inspiratory muscle strength, is easier to
perform for many NMD patients than the more commonly used determination of
maximum inspiratory pressure measured at the mouth (MIP). However, due to an
inconsistent approach in the literature, the optimal technique to perform the
SNIP maneuver is unclear. Therefore, we systematically evaluated the impact of
performing the maneuver with nostril contralateral to the pressure-sensing probe
open (SNIPOP) versus closed (SNIPCL), on determination of inspiratory muscle
strength in NMD patients as well as control subjects with normal respiratory
muscle function. METHODS: NMD patients (n = 52) and control subjects without
respiratory dysfunction (n = 52) were studied. SNIPOP, SNIPCL, and MIP were
measured during the same session and compared using ANOVA. Agreement and bias
were assessed with intraclass correlation coefficients (ICC) and Bland-Altman
plots. RESULTS: Mean MIP values were 58.2 and 94.0 cmH2O in NMD and control
subjects, respectively (p<0.001). SNIPCL was greater than SNIPOP in NMD (51.9 +/
31.0 vs. 36.9 +/-25.4 cmH2O; p<0.001) as well as in controls (89.2 +/-28.1 vs.
69.2 +/-29.2 cmH2O; p<0.001). In both populations, the ICC between MIP and SNIPCL
(NMD = 0.78, controls = 0.35) was higher than for MIP and SNIPOP (NMD = 0.53,
controls = 0.06). In addition, SNIPCL was more often able to exclude inspiratory
muscle weakness than SNIPOP. CONCLUSIONS: SNIPCL values are systematically higher
than SNIPOP in both normal subjects and NMD patients. Therefore, SNIPCL is a
useful complementary test for ruling out inspiratory muscle weakness in
individuals with low MIP values.
PMID- 28520770
TI - Life history trade-off moderates model predictions of diversity loss from climate
change.
AB - Climate change can trigger species range shifts, local extinctions and changes in
diversity. Species interactions and dispersal capacity are important mediators of
community responses to climate change. The interaction between multispecies
competition and variation in dispersal capacity has recently been shown to
exacerbate the effects of climate change on diversity and to increase predictions
of extinction risk dramatically. Dispersal capacity, however, is part of a
species' overall ecological strategy and are likely to trade off with other
aspects of its life history that influence population growth and persistence. In
plants, a well-known example is the trade-off between seed mass and seed number.
The presence of such a trade-off might buffer the diversity loss predicted by
models with random but neutral (i.e. not impacting fitness otherwise) differences
in dispersal capacity. Using a trait-based metacommunity model along a warming
climatic gradient the effect of three different dispersal scenarios on model
predictions of diversity change were compared. Adding random variation in species
dispersal capacity caused extinctions by the introduction of strong fitness
differences due an inherent property of the dispersal kernel. Simulations
including a fitness-equalising trade-off based on empirical relationships between
seed mass (here affecting dispersal distance, establishment probability, and
seedling biomass) and seed number (fecundity) maintained higher initial species
diversity and predicted lower extinction risk and diversity loss during climate
change than simulations with variable dispersal capacity. Large seeded species
persisted during climate change, but developed lags behind their climate niche
that may cause extinction debts. Small seeded species were more extinction-prone
during climate change but tracked their niches through dispersal and
colonisation, despite competitive resistance from residents. Life history trade
offs involved in coexistence mechanisms may increase community resilience to
future climate change and are useful guides for model development.
PMID- 28520771
TI - Quality of maternity care and its determinants along the continuum in Kenya: A
structural equation modeling analysis.
AB - BACKGROUND: Improving access to delivery services does not guarantee access to
quality obstetric care and better survival, and therefore, concerns for quality
of maternal and newborn care in low- and middle-income countries have been
raised. Our study explored characteristics associated with the quality of initial
assessment, intrapartum, and immediate postpartum and newborn care, and further
assessed the relationships along the continuum of care. METHODS: The 2010 Service
Provision Assessment data of Kenya for 627 routine deliveries of women aged 15-49
were used. Quality of care measures were assessed using recently validated
quality of care measures during initial assessment, intrapartum, and postpartum
periods. Data were analyzed with negative binomial regression and structural
equation modeling technique. RESULTS: The negative binomial regression results
identified a number of determinants of quality, such as the level of health
facilities, managing authority, presence of delivery fee, central electricity
supply and clinical guideline for maternal and neonatal care. Our structural
equation modeling (SEM) further demonstrated that facility characteristics were
important determinants of quality for initial assessment and postpartum care,
while characteristics at the provider level became more important in shaping the
quality of intrapartum care. Furthermore we also noted that quality of initial
assessment had a positive association with quality of intrapartum care (beta =
0.71, p < 0.001), which in turn was positively associated with the quality of
newborn and immediate postpartum care (beta = 1.29, p = 0.004). CONCLUSIONS: A
continued focus on quality of care along the continuum of maternity care is
important not only to mothers but also their newborns. Policymakers should
therefore ensure that required resources, as well as adequate supervision and
emphasis on the quality of obstetric care, are available.
PMID- 28520772
TI - The chicken embryo as an efficient model to test the function of muscle fusion
genes in amniotes.
AB - The fusion of myoblasts into multinucleated myotubes is a crucial step of muscle
growth during development and of muscle repair in the adult. While multiple genes
were shown to play a role in this process, a vertebrate model where novel
candidates can be tested and analyzed at high throughput and relative ease has
been lacking. Here, we show that the early chicken embryo is a fast and robust
model in which functional testing of muscle fusion candidate genes can be
performed. We have used known modulators of muscle fusion, Rac1 and Cdc42, along
with the in vivo electroporation of integrated, inducible vectors, to show that
the chicken embryo is a suitable model in which their function can be tested and
quantified. In addition to nuclei content, specific characteristics of the
experimental model allow a fine characterization of additional morphological
features that are nearly impossible to assess in other model organisms. This
study should establish the chicken embryo as a cheap, reliable and powerful model
in which novel vertebrate muscle fusion candidates can be evaluated.
PMID- 28520773
TI - Development of the "Highly Sensitive Dog" questionnaire to evaluate the
personality dimension "Sensory Processing Sensitivity" in dogs.
AB - In humans, the personality dimension 'sensory processing sensitivity (SPS)', also
referred to as "high sensitivity", involves deeper processing of sensory
information, which can be associated with physiological and behavioral
overarousal. However, it has not been studied up to now whether this dimension
also exists in other species. SPS can influence how people perceive the
environment and how this affects them, thus a similar dimension in animals would
be highly relevant with respect to animal welfare. We therefore explored whether
SPS translates to dogs, one of the primary model species in personality research.
A 32-item questionnaire to assess the "highly sensitive dog score" (HSD-s) was
developed based on the "highly sensitive person" (HSP) questionnaire. A large
scale, international online survey was conducted, including the HSD
questionnaire, as well as questions on fearfulness, neuroticism, "demographic"
(e.g. dog sex, age, weight; age at adoption, etc.) and "human" factors (e.g.
owner age, sex, profession, communication style, etc.), and the HSP
questionnaire. Data were analyzed using linear mixed effect models with forward
stepwise selection to test prediction of HSD-s by the above-mentioned factors,
with country of residence and dog breed treated as random effects. A total of
3647 questionnaires were fully completed. HSD-, fearfulness, neuroticism and HSP
scores showed good internal consistencies, and HSD-s only moderately correlated
with fearfulness and neuroticism scores, paralleling previous findings in humans.
Intra- (N = 447) and inter-rater (N = 120) reliabilities were good. Demographic
and human factors, including HSP score, explained only a small amount of the
variance of HSD-s. A PCA analysis identified three subtraits of SPS, comparable
to human findings. Overall, the measured personality dimension in dogs showed
good internal consistency, partial independence from fearfulness and neuroticism,
and good intra- and inter-rater reliability, indicating good construct validity
of the HSD questionnaire. Human and demographic factors only marginally affected
the HSD-s suggesting that, as hypothesized for human SPS, a genetic basis may
underlie this dimension within the dog species.
PMID- 28520774
TI - Affective responses in mountain hiking-A randomized crossover trial focusing on
differences between indoor and outdoor activity.
AB - INTRODUCTION: Affective responses during physical activity (PA) are important for
engagement in PA programs and for adherence to a physically active lifestyle.
Little is known about the affective responses to PA bouts lasting longer than 45
minutes. Therefore, the aims of the present study were to analyse acute effects
on affective responses of a three-hour outdoor PA intervention (mountain hiking)
compared to a sedentary control situation and to an indoor treadmill condition.
METHODS: Using a randomized crossover design, 42 healthy participants were
randomly exposed to three different conditions: outdoor mountain hiking, indoor
treadmill walking, and sedentary control situation (approximately three hours
each). Measures included the Feeling Scale, Felt Arousal Scale and a Mood Survey
Scale. Repeated measures ANOVAs were used to analyse differences between the
conditions. RESULTS: Compared to the control situation, the participants showed a
significant increase in affective valence (d = 1.21, p < .001), activation (d =
0.81, p = .004), elation (d = 1.07, p < .001), and calmness (d = 0.84, p = .004),
and a significant decrease in fatigue (d = -1.19, p < .001) and anxiety (d =
.79, p < .001) after mountain hiking. Outdoor mountain hiking showed
significantly greater positive effects on affective valence, activation, and
fatigue compared to indoor treadmill walking. DISCUSSION: The results indicate
that a three-hour PA intervention (mountain hiking) elicits higher positive and
lower negative affective responses compared to a sedentary control situation and
to an indoor PA condition. Outdoor mountain hiking can be recommended by health
professionals as a form of PA with the potential to positively influence
affective responses. TRIAL REGISTRATION: ClinicalTrials.gov NCT02853760.
https://clinicaltrials.gov/. Date of registration: 08/02/2016 (retrospectively
registered). Date of enrolment of the first participant to the trial: 05/01/2014.
PMID- 28520775
TI - Sex differences in neuromuscular androgen receptor expression and sociosexual
behavior in a sex changing fish.
AB - Androgen signaling, via receptor binding, is critical for regulating the
physiological and morphological foundations of male-typical reproductive behavior
in vertebrates. Muscles essential for male courtship behavior and copulation are
highly sensitive to androgens. Differences in the distribution and density of the
androgen receptor (AR) are important for maintaining dimorphic musculature and
thus may provide for anatomical identification of sexually selected traits. In
Lythrypnus dalli, a bi-directional hermaphroditic teleost fish, both sexes
produce agonistic approach displays, but reproductive behavior is sexually
dimorphic. The male-specific courtship behavior is characterized by rapid jerky
movements (involving dorsal fin erection) towards a female or around their nest.
Activation of the supracarinalis muscle is involved in dorsal fin contributions
to both agonistic and sociosexual behavior in other fishes, suggesting that
differences in goby sexual behavior may be reflected in sexual dimorphism in AR
signaling in this muscle. We examined sex differences in the local distribution
of AR in supracarinalis muscle and spinal cord. Our results demonstrate that
males do express more AR in the supracarinalis muscle relative to females, but
there was no sex difference in the number of spinal motoneurons expressing AR.
Interestingly, AR expression in the supracarinalis muscle was also related to
rates of sociosexual behavior in males, providing evidence that sexual selection
may influence muscle androgenic sensitivity to enhance display vigor. Sex
differences in the distribution and number of cells expressing AR in the
supracarinalis muscle may underlie the expression of dimorphic behaviors in L.
dalli.
PMID- 28520776
TI - Proteomic analysis of tea plants (Camellia sinensis) with purple young shoots
during leaf development.
AB - Tea products made from purple leaves are highly preferred by consumers due to the
health benefits. This study developed a proteome reference map related to color
changes during leaf growth in tea (Camellia sinensis) plant with purple young
shoots using two-dimensional electrophoresis (2-DE). Forty-six differentially
expressed proteins were detected in the gel and successfully identified by using
MALDI-TOF/TOF-MS. The pronounced changes in the proteomic profile between tender
purple leaves (TPL) and mature green leaves (MGL) included: 1) the lower activity
of proteins associated with CO2 assimilation, energy metabolism and photo flux
efficiency and higher content of anthocyanins in TPL than those in MGL may
protect tender leaves against photo-damage; 2) the higher abundance of chalcone
synthase (CHS), chalcone isomerase (CHI) and flavonol synthase (FLS) likely
contributes to the synthesis of anthocyanins, catechins and flavonols in TPL
tissues; 3) higher abundance of stress response proteins, such as glutathione S
transferases (GST) and phospholipid hydroperoxide glutathione peroxidase (PHGPx),
could enhance the tolerance of TPL tissues to adverse condition in; and 4) the
increased abundance of proteins related to protein synthesis, nucleic acids and
cell wall proteins should be beneficial for the proliferation and expansion of
leaf cell in TPL tissues. qPCR analysis showed that the expression of
differentially abundant proteins was regulated at the transcriptional level.
Therefore, the results indicated that higher abundance of CHI and CHS may account
for the production of the purple-shoot phenotype in Wuyiqizhong 18 and thereby,
enhancing the anthocyanin biosynthesis. The higher abundance of glutamine
synthetase (GS) proteins related to the theanine biosynthesis may improve the
flavor of tea products from TPL materials. Thus, this work should help to
understand the molecular mechanisms underlying the changes in leaf color
alteration.
PMID- 28520777
TI - Network based stratification of major cancers by integrating somatic mutation and
gene expression data.
AB - The stratification of cancer into subtypes that are significantly associated with
clinical outcomes is beneficial for targeted prognosis and treatment. In this
study, we integrated somatic mutation and gene expression data to identify
clusters of patients. In contrast to previous studies, we constructed cancer-type
specific significant co-expression networks (SCNs) rather than using a fixed gene
network across all cancers, such as the network-based stratification (NBS)
method, which ignores cancer heterogeneity. For each type of cancer, the gene
expression data were used to construct the SCN network, while the gene somatic
mutation data were mapped onto the network, propagated, and used for further
clustering. For the clustering, we adopted an improved network-regularized non
negative matrix factorization (netNMF) (netNMF_HC) for a more precise
classification. We applied our method to various datasets, including ovarian
cancer (OV), lung adenocarcinoma (LUAD) and uterine corpus endometrial carcinoma
(UCEC) cohorts derived from the TCGA (The Cancer Genome Atlas) project. Based on
the results, we evaluated the performance of our method to identify survival
relevant subtypes and further compared it to the NBS method, which adopts priori
networks and netNMF algorithm. The proposed algorithm outperformed the NBS method
in identifying informative cancer subtypes that were significantly associated
with clinical outcomes in most cancer types we studied. In particular, our method
identified survival-associated UCEC subtypes that were not identified by the NBS
method. Our analysis indicated valid subtyping of patient could be applied by
mutation data with cancer-type-specific SCNs and netNMF_HC for individual cancers
because of specific cancer co-expression patterns and more precise clustering.
PMID- 28520778
TI - Texture analysis using proton density and T2 relaxation in patients with
histological usual interstitial pneumonia (UIP) or nonspecific interstitial
pneumonia (NSIP).
AB - OBJECTIVES: The purpose of our study was to assess proton density (PD) and T2
relaxation time of usual interstitial pneumonia (UIP) and nonspecific
interstitial pneumonia (NSIP) and to evaluate their utility in differentiating
the two patterns. Furthermore, we aim to investigate whether these two parameters
could help differentiate active-inflammatory and stable-fibrotic lesions in NSIP.
METHODS: 32 patients (mean age: 69 years; M:F, 1:1) with pathologically proven
disease (UIP:NSIP, 1:1), underwent thoracic thin-section multislice CT scan and
1.5T MRI. A total of 437 regions-of-interest (ROIs) were classified at CT as
advanced, moderate or mild alterations. Based on multi-echo single-shot TSE
sequence acquired at five echo times, with breath-holding at end-expiration and
ECG-triggering, entire lung T2 and PD maps were generated from each subject. The
T2 relaxation time and the respective signal intensity were quantified by
performing a ROI measurement on the T2 and PD maps in the corresponding CT
selected areas of the lung. RESULTS: UIP and NSIP regional patterns could not be
differentiated by T2 relaxation times or PD values alone. Overall, a strong
positive correlation was found between T2 relaxation and PD in NSIP, r = 0.64,
p<0.001; however, this correlation was weak in UIP, r = 0.20, p = 0.01. T2
relaxation showed significant statistical difference between active-inflammatory
and stable-fibrotic NSIP regions at all levels, p<0.05, while for the analysis of
ventral lesions PD proved no statistical difference, p>0.05. CONCLUSIONS: T2
relaxation times and PD values may provide helpful quantitative information for
differentiating NSIP from UIP pattern. These parameters have the potential to
differentiate active-inflammatory and stable-fibrotic lesions in NSIP.
PMID- 28520780
TI - Towards a point-of-care strip test to diagnose sickle cell anemia.
AB - A rapid test to identify patients with sickle cell disease could have important
benefits in low-resource settings. Sickle cell anemia (SCA) affects about 300,000
newborns each year, the majority of whom are born in sub-Saharan Africa. Low-cost
therapies are available to treat SCA, but most countries in sub-Saharan Africa
lack robust neonatal screening programs needed to identify patients in need of
treatment. To address this need, we developed and evaluated a competitive lateral
flow assay that identifies patients with SCA (genotype HbSS) in 15 minutes using
undiluted whole blood. A small volume of blood (0.5 MUL- 3 MUL) is mixed with
antibody-coated blue latex beads in a tube and applied to the strip. Strips are
then placed in a well of running buffer and allowed to run for 10 minutes.
Laboratory evaluation with samples containing different proportions of hemoglobin
A (HbA) and hemoglobin S (HbS) indicated that the test should enable
identification of SCA patients but not persons with sickle cell trait (SCT). We
evaluated the test using 41 samples from individuals with SCA, SCT, and normal
blood. With visual inspection or quantitative analysis, we found a 98% accuracy
when differentiating SCA from normal and SCT samples as a group (90% sensitivity
and 100% specificity for identifying SCA). This work demonstrates important steps
towards making a lateral flow test for hemoglobinopathies more appropriate for
point-of-care use; further work is needed before the test is appropriate for
clinical use.
PMID- 28520779
TI - Church attendance, allostatic load and mortality in middle aged adults.
AB - IMPORTANCE: Religiosity has been associated with positive health outcomes.
Hypothesized pathways for this association include religious practices, such as
church attendance, that result in reduced stress. OBJECTIVE: The objective of
this study was to examine the relationship between religiosity (church
attendance), allostatic load (AL) (a physiologic measure of stress) and all-cause
mortality in middle-aged adults. DESIGN, SETTING AND PARTICIPANTS: Data for this
study are from NHANES III (1988-1994). The analytic sample (n = 5449) was
restricted to adult participants, who were between 40-65 years of age at the time
of interview, had values for at least 9 out of 10 clinical/biologic markers used
to derive AL, and had complete information on church attendance. MAIN OUTCOMES
AND MEASURES: The primary outcomes were AL and mortality. AL was derived from
values for metabolic, cardiovascular, and nutritional/inflammatory
clinical/biologic markers. Mortality was derived from a probabilistic algorithm
matching the NHANES III Linked Mortality File to the National Death Index through
December 31, 2006, providing up to 18 years follow-up. The primary predictor
variable was baseline report of church attendance over the past 12 months. Cox
proportional hazard logistic regression models contained key covariates including
socioeconomic status, self-rated health, co-morbid medical conditions, social
support, healthy eating, physical activity, and alcohol intake. RESULTS:
Churchgoers (at least once a year) comprised 64.0% of the study cohort (n =
3782). Non-churchgoers had significantly higher overall mean AL scores and higher
prevalence of high-risk values for 3 of the 10 markers of AL than did
churchgoers. In bivariate analyses non-churchgoers, compared to churchgoers, had
higher odds of an AL score 2-3 (OR 1.24; 95% CI 1.01, 1.50) or >=4 (OR 1.38; 95%
CI 1.11, 1.71) compared to AL score of 0-1. More frequent churchgoers (more than
once a week) had a 55% reduction of all-cause mortality risk compared with non
churchgoers. (HR 0.45, CI 0.24-0.85) in the fully adjusted model that included
AL. CONCLUSIONS AND RELEVANCE: We found a significant association between church
attendance and mortality among middle-aged adults after full adjustments. AL, a
measure of stress, only partially explained differences in mortality between
church and non-church attendees. These findings suggest a potential independent
effect of church attendance on mortality.
PMID- 28520782
TI - Adaptive double threshold energy detection based on Markov model for cognitive
radio.
AB - The rapid development in the area of cognitive radio technology leads the society
to higher standards of spectrum sensing performance, particularly in low signal
to-noise ratio (SNR) environment. This article proposes an adaptive double
threshold energy sensing method based on Markov model (ADEMM). When using the
double-threshold energy sensing method, the modified Markov model that accounts
for the time varying characteristic of the channel occupancy was presented to
resolve the 'confused' channel state. Furthermore, in order to overcome the
effect of noise uncertainty, the findings of this article introduce an adaptive
double-threshold spectrum sensing method that adjusts its thresholds according to
the achievable maximal detection probability. Numerical simulations show that the
proposed ADEMM achieves better detection performance than the conventional double
threshold energy sensing schemes, especially in very low SNR region.
PMID- 28520781
TI - Physical activity and sedentary behaviour in daily life: A comparative analysis
of the Global Physical Activity Questionnaire (GPAQ) and the SenseWear armband.
AB - Reduction of sedentary time and an increase in physical activity offer potential
to improve public health. However, quantifying physical activity behaviour under
real world conditions is a major challenge and no standard of good practice is
available. Our aim was to compare the results of physical activity and sedentary
behaviour obtained with a self-reported instrument (Global Physical Activity
Questionnaire (GPAQ)) and a wearable sensor (SenseWear) in a repeated measures
study design. Healthy adults (41 in Antwerp, 41 in Barcelona and 40 in London)
wore the SenseWear armband for seven consecutive days and completed the GPAQ on
the final day. This was repeated three times. We used the Wilcoxon signed rank
sum test, Spearman correlation coefficients, mixed effects regression models and
Bland-Altman plots to study agreement between both methods. Mixed models were
used to assess the effect of personal characteristics on the absolute and
relative difference between estimates obtained with the GPAQ and SenseWear.
Moderate to vigorous energy expenditure and duration derived from the GPAQ were
significantly lower (p<0.05) compared to the SenseWear, yet these variables
showed significant correlations ranging from 0.45 to 0.64. Estimates of vigorous
intensity physical activity in particular showed high similarity (r>0.59).
Results for sedentary behaviour did not differ, yet were poorly correlated
(r<0.25). The differences between all variables were reproducible across repeated
measurements. In addition, we observed a relationship between these differences
and BMI, body fat and physical activity domain. Due to the lack of a standardized
protocol, results from different studies measuring physical activity and
sedentary behaviour are difficult to compare. Therefore, we suggested an easy-to
implement approach for future studies adding the GPAQ to the wearable of choice
as a basis for comparisons.
PMID- 28520783
TI - Effect of N-terminal region of nuclear Drosophila melanogaster small heat shock
protein DmHsp27 on function and quaternary structure.
AB - The importance of the N-terminal region (NTR) in the oligomerization and
chaperone-like activity of the Drosophila melanogaster small nuclear heat shock
protein DmHsp27 was investigated by mutagenesis using size exclusion
chromatography and native gel electrophoresis. Mutation of two sites of
phosphorylation in the N-terminal region, S58 and S75, did not affect the
oligomerization equilibrium or the intracellular localization of DmHsp27 when
transfected into mammalian cells. Deletion or mutation of specific residues
within the NTR region delineated a motif (FGFG) important for the oligomeric
structure and chaperone-like activity of this sHsp. While deletion of the full N
terminal region, resulted in total loss of chaperone-like activity, removal of
the (FGFG) at position 29 to 32 or single mutation of F29A/Y, G30R and G32R
enhanced oligomerization and chaperoning capacity under non-heat shock conditions
in the insulin assay suggesting the importance of this site for chaperone
activity. Unlike mammalian sHsps DmHsp27 heat activation leads to enhanced
association of oligomers to form large structures of approximately 1100 kDa. A
new mechanism of thermal activation for DmHsp27 is presented.
PMID- 28520784
TI - Presynaptic Abeta40 prevents synapse addition in the adult Drosophila
neuromuscular junction.
AB - Complexity in the processing of the Amyloid Precursor Protein, which generates a
mixture of betaamyloid peptides, lies beneath the difficulty in understanding the
etiology of Alzheimer's disease. Moreover, whether Abeta peptides have any
physiological role in neurons is an unresolved question. By expressing single,
defined Abeta peptides in Drosophila, specific effects can be discriminated in
vivo. Here, we show that in the adult neuromuscular junction (NMJ), presynaptic
expression of Abeta40 hinders the synaptic addition that normally occurs in
adults, yielding NMJs with an invariable number of active zones at all ages
tested. A similar trend is observed for Abeta42 at young ages, but net synaptic
loss occurs at older ages in NMJs expressing this amyloid species. In contrast,
Abeta42arc produces net synaptic loss at all ages tested, although age-dependent
synaptic variations are maintained. Inhibition of the PI3K synaptogenic pathway
may mediate some of these effects, because western analyses show that Abeta
peptides block activation of this pathway, and Abeta species-specific
synaptotoxic effects persists in NMJs overgrown by over-expression of PI3K.
Finally, individual Abeta effects are also observed when toxicity is examined by
quantifying neurodegeneration and survival. Our results suggest a physiological
effect of Abeta40 in synaptic plasticity, and imply different toxic mechanisms
for each peptide species.
PMID- 28520785
TI - Prospective evidence for independent nitrogen and phosphorus limitation of
grasshopper (Chorthippus curtipennis) growth in a tallgrass prairie.
AB - Insect herbivores play a pivotal role in regulating plant production and
community composition, and their role in terrestrial ecosystems is partly
determined by their feeding behavior and performance among plants of differing
nutritional quality. Historically, nitrogen (N) has been considered the primary
limiting nutrient of herbivorous insects, but N is only one of many potential
nutrients important to insect performance. Of these nutrients, phosphorus (P) is
perhaps the most important because somatic growth depends upon P-rich ribosomal
RNA. Yet relatively few studies have assessed the strength of P-limitation for
terrestrial insects and even fewer have simultaneously manipulated both N and P
to assess the relative strengths of N- and P-limitation. Here, we tested for
potential N and P limitation, as well as N:P co-limitation, on Chorthippis
curtipennis (Orthoptera, Acrididae), an abundant member of arthropod communities
of central US prairies. Our results demonstrate weak evidence for both N and P
limitation of C. curtipennis growth rates in laboratory feeding assays.
Importantly, P-limitation was just as strong as N-limitation, but we found no
evidence for NP co-limitation in our study. Furthermore, nutrient limitation was
not apparent in field studies, suggesting that insect growth rates may be
predominately controlled by other factors, including temperature and predation.
Our results suggest that P should be jointly considered, along with N, as a
primary determinant of herbivore feeding behavior under both current and future
climate conditions.
PMID- 28520786
TI - A systematic genetic screen for genes involved in sensing inorganic phosphate
availability in Saccharomyces cerevisiae.
AB - Saccharomyces cerevisiae responds to changes in extracellular inorganic phosphate
(Pi) availability by regulating the activity of the phosphate-responsive (PHO)
signaling pathway, enabling cells to maintain intracellular levels of the
essential nutrient Pi. Pi-limitation induces upregulation of inositol
heptakisphosphate (IP7) synthesized by the inositol hexakisphosphate kinase Vip1,
triggering inhibition of the Pho80/Pho85 cyclin-cyclin dependent kinase (CDK)
complex by the CDK inhibitor Pho81, which upregulates the PHO regulon through the
CDK target and transcription factor Pho4. To identify genes that are involved in
signaling upstream of the Pho80/Pho85/Pho81 complex and how they interact with
each other to regulate the PHO pathway, we performed genome-wide screens with the
synthetic genetic array method. We identified more than 300 mutants with defects
in signaling upstream of the Pho80/Pho85/Pho81 complex, including AAH1, which
encodes an adenine deaminase that negatively regulates the PHO pathway in a Vip1
dependent manner. Furthermore, we showed that even in the absence of VIP1, the
PHO pathway can be activated under prolonged periods of Pi starvation, suggesting
complexity in the mechanisms by which the PHO pathway is regulated.
PMID- 28520788
TI - Correction: Barriers to Timely and Safe Blood Transfusion for PPH Patients:
Evidence from a Qualitative Study in Dhaka, Bangladesh.
AB - [This corrects the article DOI: 10.1371/journal.pone.0167399.].
PMID- 28520787
TI - Development of an R4 dual-site (R4DS) gateway cloning system enabling the
efficient simultaneous cloning of two desired sets of promoters and open reading
frames in a binary vector for plant research.
AB - Vast numbers of proteins work cooperatively to exert their functions in various
cells. In order to understand the functions and molecular mechanisms of these
proteins in plants, analyses of transgenic plants that concomitantly express two
protein-coding genes are often required. We developed a novel Gateway cloning
technology-compatible binary vector system, the R4 dual-site (R4DS) Gateway
cloning system, which enables the easy and efficient cloning of two desired sets
of promoters and open reading frames (ORFs) into a binary vector using promoter
and ORF entry clones. In this system, C-terminal fusions with 17 kinds of tags
including visible reporters and epitope tags are available for each ORF, and
selection by four kinds of resistance markers is possible. We verified that the
R4DS Gateway cloning system functioned well in Arabidopsis thaliana by observing
the expression and localization patterns of fluorescent proteins fused with
organelle-targeting signals and driven by stomatal-lineage specific promoters. We
also confirmed that the two cloning sites in the R4DS Gateway cloning system were
equivalent and independently regulated. The results obtained indicate that the
R4DS Gateway cloning system facilitates detailed comparisons of the expression
patterns of two promoters as well as co-localization and interaction analyses of
two proteins in specific cells in plants.
PMID- 28520790
TI - Correction: A Novel Quantitative Hemolytic Assay Coupled with Restriction
Fragment Length Polymorphisms Analysis Enabled Early Diagnosis of Atypical
Hemolytic Uremic Syndrome and Identified Unique Predisposing Mutations in Japan.
AB - [This corrects the article DOI: 10.1371/journal.pone.0124655.].
PMID- 28520789
TI - Antigen-specific immunoglobulin variable region sequencing measures humoral
immune response to vaccination in the equine neonate.
AB - The value of prophylactic neonatal vaccination is challenged by the interference
of passively transferred maternal antibodies and immune competence at birth.
Taken our previous studies on equine B cell ontogeny, we hypothesized that the
equine neonate generates a diverse immunoglobulin repertoire in response to
vaccination, independently of circulating maternal antibodies. In this study,
equine neonates were vaccinated with 3 doses of keyhole limpet hemocyanin (KLH)
or equine influenza vaccine, and humoral immune responses were assessed using
antigen-specific serum antibodies and B cell Ig variable region sequencing. An
increase (p<0.0001) in serum KLH-specific IgG level was measured between days 21
and days 28, 35 and 42 in vaccinated foals from non-vaccinated mares. In
vaccinated foals from vaccinated mares, serum KLH-specific IgG levels tended to
increase at day 42 (p = 0.07). In contrast, serum influenza-specific IgG levels
rapidly decreased (p<=0.05) in vaccinated foals from vaccinated mares within the
study period. Nevertheless, IGHM and IGHG sequences were detected in KLH- and
influenza- sorted B cells of vaccinated foals, independently of maternal
vaccination status. Immunoglobulin nucleotide germline identity, IGHV gene usage
and CDR length of antigen-specific IGHG sequences in B cells of vaccinated foals
revealed a diverse immunoglobulin repertoire with isotype switching that was
comparable between groups and to vaccinated mares. The low expression of CD27
memory marker in antigen-specific B cells, and of cytokines in peripheral blood
mononuclear cells upon in vitro immunogen stimulation indicated limited
lymphocyte population expansion in response to vaccine during the study period.
PMID- 28520791
TI - Toxic and hormetic-like effects of three components of citrus essential oils on
adult Mediterranean fruit flies (Ceratitis capitata).
AB - Plant essential oils (EOs) and a wide range of their individual components are
involved in a variety of biological interactions with insect pests including
stimulatory, deterrent, toxic and even hormetic effects. Both the beneficial and
toxic properties of citrus EOs on the Mediterranean fruit fly (medfly) have been
experimentally evidenced over the last years. However, no information is
available regarding the toxic or beneficial effects of the major components of
citrus EOs via contact with the adults of the Mediterranean fruit fly. In the
present study, we explored the toxicity of limonene, linalool and alpha-pinene (3
of the main compounds of citrus EOs) against adult medflies and identified the
effects of sub-lethal doses of limonene on fitness traits in a relaxed [full diet
(yeast and sugar)] and in a stressful (sugar only) feeding environment. Our
results demonstrate that all three compounds inferred high toxicity to adult
medflies regardless of the diet, with males being more sensitive than females.
Sub-lethal doses of limonene (LD20) enhanced the lifespan of adult medflies when
they were deprived of protein. Fecundity was positively affected when females
were exposed to limonene sub-lethal doses. Therefore, limonene, a major
constituent of citrus EOs, induces high mortality at increased doses and positive
effects on life history traits of medfly adults through contact at low sub-lethal
doses. A hormetic-like effect of limonene to adult medflies and its possible
underlying mechanisms are discussed.
PMID- 28520793
TI - How does motion affect GABA-measurements? Order statistic filtering compared to
conventional analysis of MEGA-PRESS MRS.
AB - PURPOSE: The aim of this study was to evaluate two post-processing techniques
applied to MRS MEGA-PRESS data influenced by motion-induced artifacts. In
contrast to the conventional averaging technique, order statistic filtering (OSF)
is a known method for artifact reduction. Therefore, this method may be suitable
to incorporate in the GABA quantification. METHODS: Twelve healthy volunteers
were scanned three times using a 3 T MR system. One measurement protocol
consisted of two MEGA-PRESS measurements, one reference measurement and one
measurement including head motions. The resulting datasets were analyzed with the
standard averaging technique and with the OSF-technique in two schemes; filtering
phase cycles 'RAW PC' and filtering dynamics 'RAW Dyn'. RESULTS: The datasets
containing artifacts resulted in an underestimation of the concentrations. There
was a trend for the OSF-technique to compensate for this reduction when
quantifying SNR-intense signals. However, there was no indication that OSF
improved the estimated GABA concentrations. Moreover, when only considering the
reference measurements, the OSF technique was equally as effective as averaging,
which suggests that the techniques are interchangeable. CONCLUSION: OSF performed
equally well as the conventional averaging technique for low-SNR signals. For
high-SNR signals, OSF performed better and thus could be considered for routine
usage.
PMID- 28520794
TI - The complex dynamics of products and its asymptotic properties.
AB - We analyse global export data within the Economic Complexity framework. We couple
the new economic dimension Complexity, which captures how sophisticated products
are, with an index called logPRODY, a measure of the income of the respective
exporters. Products' aggregate motion is treated as a 2-dimensional dynamical
system in the Complexity-logPRODY plane. We find that this motion can be
explained by a quantitative model involving the competition on the markets, that
can be mapped as a scalar field on the Complexity-logPRODY plane and acts in a
way akin to a potential. This explains the movement of products towards areas of
the plane in which the competition is higher. We analyse market composition in
more detail, finding that for most products it tends, over time, to a
characteristic configuration, which depends on the Complexity of the products.
This market configuration, which we called asymptotic, is characterized by higher
levels of competition.
PMID- 28520792
TI - MyD88 signaling in dendritic cells and the intestinal epithelium controls
immunity against intestinal infection with C. rodentium.
AB - MyD88-mediated signaling downstream of Toll-like receptors and the IL-1 receptor
family is critically involved in the induction of protective host responses upon
infections. Although it is known that MyD88-deficient mice are highly susceptible
to a wide range of bacterial infections, the cell type-specific contribution of
MyD88 in protecting the host against intestinal bacterial infection is only
poorly understood. In order to investigate the importance of MyD88 in specific
immune and nonimmune cell types during intestinal infection, we employed a novel
murine knock-in model for MyD88 that enables the cell type-specific reactivation
of functional MyD88 expression in otherwise MyD88-deficient mice. We report here
that functional MyD88 signaling in CD11c+ cells was sufficient to activate
intestinal dendritic cells (DC) and to induce the early group 3 innate lymphoid
cell (ILC3) response as well as the development of colonic Th17/Th1 cells in
response to infection with the intestinal pathogen C. rodentium. In contrast,
restricting MyD88 signaling to several other cell types, including macrophages
(MO), T cells or ILC3 did not induce efficient intestinal immune responses upon
infection. However, we observed that the functional expression of MyD88 in
intestinal epithelial cells (IEC) also partially protected the mice during
intestinal infection, which was associated with enhanced epithelial barrier
integrity and increased expression of the antimicrobial peptide RegIIIgamma and
the acute phase protein SAA1 by epithelial cells. Together, our data suggest that
MyD88 signaling in DC and IEC is both essential and sufficient to induce a full
spectrum of host responses upon intestinal infection with C. rodentium.
PMID- 28520796
TI - A hierarchical model for estimating the spatial distribution and abundance of
animals detected by continuous-time recorders.
AB - MOTIVATION: Several spatial capture-recapture (SCR) models have been developed to
estimate animal abundance by analyzing the detections of individuals in a spatial
array of traps. Most of these models do not use the actual dates and times of
detection, even though this information is readily available when using
continuous-time recorders, such as microphones or motion-activated cameras.
Instead most SCR models either partition the period of trap operation into a set
of subjectively chosen discrete intervals and ignore multiple detections of the
same individual within each interval, or they simply use the frequency of
detections during the period of trap operation and ignore the observed times of
detection. Both practices make inefficient use of potentially important
information in the data. MODEL AND DATA ANALYSIS: We developed a hierarchical SCR
model to estimate the spatial distribution and abundance of animals detected with
continuous-time recorders. Our model includes two kinds of point processes: a
spatial process to specify the distribution of latent activity centers of
individuals within the region of sampling and a temporal process to specify
temporal patterns in the detections of individuals. We illustrated this SCR model
by analyzing spatial and temporal patterns evident in the camera-trap detections
of tigers living in and around the Nagarahole Tiger Reserve in India. We also
conducted a simulation study to examine the performance of our model when
analyzing data sets of greater complexity than the tiger data. BENEFITS: Our
approach provides three important benefits: First, it exploits all of the
information in SCR data obtained using continuous-time recorders. Second, it is
sufficiently versatile to allow the effects of both space use and behavior of
animals to be specified as functions of covariates that vary over space and time.
Third, it allows both the spatial distribution and abundance of individuals to be
estimated, effectively providing a species distribution model, even in cases
where spatial covariates of abundance are unknown or unavailable. We illustrated
these benefits in the analysis of our data, which allowed us to quantify
differences between nocturnal and diurnal activities of tigers and to estimate
their spatial distribution and abundance across the study area. Our continuous
time SCR model allows an analyst to specify many of the ecological processes
thought to be involved in the distribution, movement, and behavior of animals
detected in a spatial trapping array of continuous-time recorders. We plan to
extend this model to estimate the population dynamics of animals detected during
multiple years of SCR surveys.
PMID- 28520795
TI - BIRC6 mediates imatinib resistance independently of Mcl-1.
AB - Baculoviral IAP repeat containing 6 (BIRC6) is a member of the inhibitors of
apoptosis proteins (IAPs), a family of functionally and structurally related
proteins that inhibit apoptosis. BIRC6 has been implicated in drug resistance in
several different human cancers, however mechanisms regulating BIRC6 have not
been extensively explored. Our phosphoproteomic analysis of an imatinib-resistant
chronic myelogenous leukemia (CML) cell line (MYL-R) identified increased amounts
of a BIRC6 peptide phosphorylated at S480, S482, and S486 compared to imatinib
sensitive CML cells (MYL). Thus we investigated the role of BIRC6 in mediating
imatinib resistance and compared it to the well-characterized anti-apoptotic
protein, Mcl-1. Both BIRC6 and Mcl-1 were elevated in MYL-R compared to MYL
cells. Lentiviral shRNA knockdown of BIRC6 in MYL-R cells increased imatinib
stimulated caspase activation and resulted in a ~20-25-fold increase in imatinib
sensitivity, without affecting Mcl-1. Treating MYL-R cells with CDK9 inhibitors
decreased BIRC6 mRNA, but not BIRC6 protein levels. By contrast, while CDK9
inhibitors reduced Mcl-1 mRNA and protein, they did not affect imatinib
sensitivity. Since the Src family kinase Lyn is highly expressed and active in
MYL-R cells, we tested the effects of Lyn inhibition on BIRC6 and Mcl-1. RNAi
mediated knockdown or inhibition of Lyn (dasatinib/ponatinib) reduced BIRC6
protein stability and increased caspase activation. Inhibition of Lyn also
increased formation of an N-terminal BIRC6 fragment in parallel with reduced
amount of the BIRC6 phosphopeptide, suggesting that Lyn may regulate BIRC6
phosphorylation and stability. In summary, our data show that BIRC6 stability is
dependent on Lyn, and that BIRC6 mediates imatinib sensitivity independently of
Mcl-1 or CDK9. Hence, BIRC6 may be a novel target for the treatment of drug
resistant CML where Mcl-1 or CDK9 inhibitors have failed.
PMID- 28520797
TI - Cytogenetic studies on populations of Camponotus rufipes (Fabricius, 1775) and
Camponotus renggeri Emery, 1894 (Formicidae: Formicinae).
AB - Two valid ant species, Camponotus rufipes and Camponotus renggeri, have recently
been the subject of a broad discussion with reference to taxa synonymization.
Both species are quite common among the Neotropical myrmecofauna and share some
unique traits, such as the shape of the scape and the pilosity patterns of the
tibiae and scapes. A single morphological trait can help distinguish these
species; however, only a combination of different approaches can enlighten our
view of the complex phylogenetic relationships prevailing in the different
populations of these two taxa. Therefore, focusing on the taxonomic issues
concerning these two species, a cytogenetic survey including 10 populations of C.
rufipes and two populations of C. renggeri was performed. In order to better
understand the extent of the relationship between C. rufipes and C. renggeri, two
common Neotropical Camponotus species, C. atriceps and C. cingulatus were taken
as outgroups. All four species of Camponotus that were studied had 2n = 40
chromosomes (4sm+34st+2t); however, the abundance of chromosome rearrangements
observed, combined with several chromosome markers, suggest that C. rufipes and
C. renggeri are two good distinct species although closely related. The already
reported chromosome translocation 2n = 39 (1m+4sm+32st+2t) for C. rufipes has
been found in different populations as in the unprecedented chromosome inversions
found both in C. rufipes and in C. renggeri populations. Within the C. renggeri
chromosome inversions, both the heterozygous state 2n = 40 (1m+3sm+34st+2t) and
the homozygous state, 2n = 40 (2m+2sm+34st+2t) were identified. However, only
heterozygous specimens for chromosome inversions were found among C. rufipes,
with karyotype configurations distinct from those found in C. renggeri, with 2n =
40 (1m+4sm+34st+2t). None of the populations studied showed signs of mosaic
individuals. With respect to rDNA clusters, the 18S rDNA seemed to be more
restricted inside the genome, as C. renggeri showed four 18S rDNA clusters,
whereas, C. rufipes, C. atriceps, and C. cingulatus showed only two clusters. The
chromosome locations of the 5S rDNA clusters were pointed for the first time in
Formicidae, and showed itself to be more widely spread over the genome. By
combining different chromosome banding approaches it was possible to demonstrate
the crucial importance that chromosome inversions played on the karyotype
evolution within these ants. The results also showed that chromosome
translocations might be a consequence of the chromatin dynamic condition observed
among Camponotus species. The homozygosis condition found in a C. renggeri from a
Brazilian savanna population for chromosome inversions and the contrasting
heterozygous condition for a different kind of chromosome inversion in C. rufipes
from the Brazilian coastal rainforest, opens the window for a chromosome race
hypothesis within the group C. renggeri and C. rufipes. The wide distribution,
rich ecological interactions, genetic diversity, and morphological variability
among C. renggeri and C. rufipes justify questioning of the actual taxonomic
status of these species. The answer of this puzzle is clear when observing the
number of 18S rDNA clusters of these ants, as C. rufipes has only two clusters
whereas C. renggeri has four.
PMID- 28520798
TI - Assessment of the accuracy of a new tool for the screening of smartphone
addiction.
AB - OBJECTIVE: To translate, adapt and validate the Smartphone Addiction Inventory
(SPAI) in a Brazilian population of young adults. METHOD: We employed the
translation and back-translation method for the adaptation of the Brazilian
version SPAI (SPAI-BR). The sample consisted of 415 university students. Data was
collected through an electronic questionnaire, which consisted of the SPAI-BR and
the Goodman Criteria (gold standard). The retests were carried out 10-15 days
after the initial tests with 130 individuals. RESULTS: The SPAI-BR maintained
semantic, idiomatic and conceptual equivalences from the original scale. The
Confirmatory Factor Analysis confirmed the One-factor model of the SPAI with good
fit indexes (x2 = 767.861, CFI = 0.913, TLI = 0.905, RMSE = 0.061, WRMR = 1.465).
The Kuder-Richardson Coefficient showed good internal consistency. The analysis
of the ROC curve established an area under the curve of 86.38%. The Intraclass
Correlation Coefficient of 0.926 between the test and the retest demonstrated an
excellent temporal stability. The high correlation between SPAI-BR and the
Goodman Criteria (rs = 0.750) established the convergent validity. CONCLUSION:
The SPAI-BR is a valid and reliable tool for the detection of Smartphone
Addiction in Brazilian university students.
PMID- 28520799
TI - Nonenzymatic glycosylation of human serum albumin and its effect on antibodies
profile in patients with diabetes mellitus.
AB - BACKGROUND: Albumin glycation and subsequent formation of advanced glycation end
products (AGEs) correlate with diabetes and associated complications. METHODS:
Human Serum Albumin (HSA) was modified with D-glucose for a 40 day period under
sterile conditions at 37 degrees C. Modified samples along with native HSA
(unmodified) were analyzed for structural modifications by UV and fluorescence,
FTIR, Liquid chromatography mass spectrometry (LCMS) and X-ray crystallography.
New-Zealand white female rabbits immunized with AGEs, represent auto-antibodies
formation as assessed by competitive and direct binding enzyme-linked
immunosorbent assay (ELISA). Neo-epitopesagainst In-vitro formed AGEs were
characterized in patients with diabetes mellitus type 2 (n = 50), type 1 (n =
50), gestational diabetes (n = 50) and type 2 with chronic kidney disease (CKD)
with eGFR level 60-89 mL/min (n = 50) from serum direct binding ELISA. RESULTS:
Glycated-HSA showed amarked increase in hyperchromicity of 65.82%,71.98%, 73.62%
and 76.63% at lambda280 nm along with anincreasein fluorescence intensity of
65.82%, 71.98%, 73.62% and 76.63% in glycated-HSA compared to native. FTIR
results showed theshifting of Amide I peak from 1656 cm_1 to 1659 cm_1 and Amide
II peak from 1554 cm_1 to 1564 cm_1 in glycated-HSA, with anew peak appearance of
carbonyl group at 1737 cm-1. LCMS chromatogram of glycated-HSA showed thepresence
of carboxymethyl lysine (CML) at 279.1 m/z. Immunological analysis showed high
antibody titre>1:12,800 in theserum of rabbits immunized with glycated-HSA
(modified with 400 mg/dL glucose) and inhibition of 84.65% at anantigen
concentration of 20MUg/mL. Maximum serum auto-antibody titre was found in T2DM
(0.517+/-0.086), T1DM (0.108+/-0.092), GDM (0.611+/-0.041) and T2DM+CKD (0.096+/
0.25) patients immunized with glycated-HSA (modified with 400 mg/dL glucose).
CONCLUSIONS: Non-enzymatic glycosylation of HSA manifests immunological
complications in diabetes mellitus due to change in its structure that enhances
neo-epitopes generation.
PMID- 28520801
TI - Group participants' experiences of a patient-directed group-based education
program for the management of type 2 diabetes mellitus.
AB - OBJECTIVE: The objective of this study was to explore the experiences of
individuals who participated in a group-based education program, including their
motivators in relation to their diabetes management, and the perceived impact of
group interactions on participants' experiences and motivation for self
management. Understanding individuals diagnosed with diabetes experiences of
group-based education for the management of type 2 diabetes mellitus may guide
the development and facilitation of these programs. METHODS: Semi-structured
interviews were conducted with all individuals who participated in the
intervention. Using thematic analysis underpinned by self-determination theory,
we developed themes that explored participants' motivators in relation to
diabetes management and the impact of group interactions on their experiences and
motivation. RESULTS: The key themes included knowledge, experience, group
interactions and motivation. Participants perceived that the group interactions
facilitated further learning and increased motivation, achieved through
normalization, peer identification or by talking with, and learning from the
experience of others. CONCLUSIONS: The results support the use of patient-centred
programs that prioritize group interactions over the didactic presentation of
content, which may address relevant psychological needs of people diagnosed with
type 2 diabetes mellitus, and improve their motivation and health behaviours.
Future group-based education programs may benefit from the use of self
determination theory as a framework for intervention design to enhance
participant motivation.
PMID- 28520800
TI - Transcriptome profiling revealed novel transcriptional regulators in maize
responses to Ostrinia furnacalis and jasmonic acid.
AB - Chewing insects cause severe yield losses in crop production worldwide. Crop
plants counteract chewing insects by transcriptionally promoting a repertoire of
defense gene products that are either toxic to, or attractive to the natural
enemies of, pest insects. However, the complexity of the transcriptional
reprogramming in plant defense response against chewing insects is still not well
understood. In this study, the genome-wide early responses in maize seedlings to
Asian corn borer (ACB, Ostrinia furnacalis) and also to jasmonic acid(JA), the
pivotal phytohormone controlling plant defense response against herbivory, were
transcriptionally profiled by RNA-Seq. Clustering of differentially expressed
genes (DEGs) along with functional enrichment analysis revealed important
biological processes regulated in response to ACB infestation and/or jasmonic
acid. Moreover, DEGs with distinct expression patterns were differentially
enriched with diverse families of cis-elements on their promoters. Multiple
inventories of differentially expressed transcription factors (DETFs) in each DEG
group were also analyzed. A transient expression assay using transfected maize
protoplastswas established to examine the potential roles of DETFs in maize
defense response and JA signaling, and this was used to show that ZmNAC60, an ACB
and JA-inducible DETF, represented a novel positive regulator of JA and defense
pathway genes. This study provided a comprehensive transcriptional picture for
the early dynamics of maize defense responses and JA signaling, and the
identification of DETFs offered potential targets for further functional genomics
investigation of master regulators in maize defense responses against herbivory.
PMID- 28520802
TI - Aquatic cycling-What do we know? A scoping review on head-out aquatic cycling.
AB - Over the past few years, aquatic cycling has become a trending fitness activity.
However, the literature has not been reviewed exhaustively. Therefore, using
scoping review methodology, the aim of this review was to explore the current
state of the literature concerning aquatic cycling. This study specifically
focused on study designs, populations and outcomes. A comprehensive search of
seven databases (PubMed, MEDLINE, Cinahl, Embase, PEDro,Web of Science, WorldCat)
was conducted up to 30th September 2016. GoogleScholar, World Cat, ResearchGate,
specific aquatic therapy websites and aquatic therapy journals were searched to
identify additional literature. Full-text publications in English, German or
Dutch were included. Studies were included when the intervention involved head
out cycling carried out in 10 degrees to 35 degrees Celsius water. Exclusion
criteria were the use of wet suits or confounding interventions that would affect
participants' homeostasis. 63 articles were included and the study parameters of
these studies were summarized. Using three grouping themes, included studies were
categorised as 1) single session tests comparing aquatic versus land cycling, or
2) aquatic cycling only sessions investigating different exercise conditions and
3) aquatic cycling intervention programmes. Although the experimental conditions
differed noticeably across the studies, shared characteristics were identified.
Cardiovascular parameters were investigated by many of the studies with the
results suggesting that the cardiac demand of aquatic cycling seems similar to
land-based cycling. Only six studies evaluated the effect of aquatic cycling
interventions. Therefore, future research should investigate the effects of
aquatic cycling interventions, preferably in individuals that are expected to
gain health benefits from aquatic cycling. Moreover, this comprehensive outline
of available literature could serve as a starting point for systematic reviews or
clinical studies on the effects of aquatic cycling on the cardiovascular
responses.
PMID- 28520804
TI - Inpatient Z-drug use commonly exceeds safe dosing recommendations.
AB - IMPORTANCE: In 2016 recommendations for safer prescribing practices were
circulated to all doctors in one of Canada's largest provinces, by the college of
physicians, following a coroner's inquest into a vehicular death related to Z
drug use. We sought to determine how frequently Z-drug prescriptions in our
institution were not adhering to these recommendations. DESIGN: Retrospective
cohort study. SETTING: McGill University Health Centre, an 832-bed tertiary care
institution in Montreal, Canada. PARTICIPANTS: All adult non-obstetrical patients
admitted between April 1, 2015 and March 31, 2016. EXPOSURE: The receipt of at
least one dose of Z-drug as determined by pharmacy records. MAIN OUTCOMES AND
MEASURES: Adherence to four recommendations related to starting dose, maximal
dose, concomitant drug administration, and duration of use were evaluated.
RESULTS: 1,409 unique patients received a Z-drug during 1,783 admissions
representing use in 9.3% of non-obstetrical patients. Standing orders were seen
in 42% (745/1783) of admissions. Non-conformity with the coroner's
recommendations was common. Overall, 672/1783 (38%) admissions involved a patient
receiving more than the recommended daily maximum dose (643/999 older patients,
64%). Of 607 admissions which were longer than 10 days, 257 (39%) involved a
prescription which exceeded 10 days. CONCLUSIONS AND RELEVANCE: A coroner's
recommendation that doctors receive instructions about safe Z-drug prescribing is
unprecedented, and was likely required given that use of Z-drugs occurs at doses
and durations that often exceed best practice recommendations. Similar
interventions may be required in other jurisdictions.
PMID- 28520803
TI - Multiple modality biomarker prediction of cognitive impairment in prospectively
followed de novo Parkinson disease.
AB - OBJECTIVES: To assess the neurobiological substrate of initial cognitive decline
in Parkinson's disease (PD) to inform patient management, clinical trial design,
and development of treatments. METHODS: We longitudinally assessed, up to 3
years, 423 newly diagnosed patients with idiopathic PD, untreated at baseline,
from 33 international movement disorder centers. Study outcomes were four
determinations of cognitive impairment or decline, and biomarker predictors were
baseline dopamine transporter (DAT) single photon emission computed tomography
(SPECT) scan, structural magnetic resonance imaging (MRI; volume and thickness),
diffusion tensor imaging (mean diffusivity and fractional anisotropy),
cerebrospinal fluid (CSF; amyloid beta [Abeta], tau and alpha synuclein), and 11
single nucleotide polymorphisms (SNPs) previously associated with PD cognition.
Additionally, longitudinal structural MRI and DAT scan data were included.
Univariate analyses were run initially, with false discovery rate = 0.2, to
select biomarker variables for inclusion in multivariable longitudinal mixed
effect models. RESULTS: By year 3, cognitive impairment was diagnosed in 15-38%
participants depending on the criteria applied. Biomarkers, some longitudinal,
predicting cognitive impairment in multivariable models were: (1) dopamine
deficiency (decreased caudate and putamen DAT availability); (2) diffuse,
cortical decreased brain volume or thickness (frontal, temporal, parietal, and
occipital lobe regions); (3) co-morbid Alzheimer's disease Abeta amyloid
pathology (lower CSF Abeta 1-42); and (4) genes (COMT val/val and BDNF val/val
genotypes). CONCLUSIONS: Cognitive impairment in PD increases in frequency 50
200% in the first several years of disease, and is independently predicted by
biomarker changes related to nigrostriatal or cortical dopaminergic deficits,
global atrophy due to possible widespread effects of neurodegenerative disease,
co-morbid Alzheimer's disease plaque pathology, and genetic factors.
PMID- 28520805
TI - Identification of key contributors in complex population structures.
AB - Evaluating the genetic contribution of individuals to population structure is
essential to select informative individuals for genome sequencing, genotype
imputation and to ascertain complex population structures. Existing methods for
the selection of informative individuals for genomic imputation solely focus on
the identification of key ancestors, which can lead to a loss of phasing accuracy
of the reference population. Currently many methods are independently applied to
investigate complex population structures. Based on the Eigenvalue Decomposition
(EVD) of a genomic relationship matrix we describe a novel approach to evaluate
the genetic contribution of individuals to population structure. We combined the
identification of key contributors with model-based clustering and population
network visualization into an integrated three-step approach, which allows
identification of high-resolution population structures and substructures around
such key contributors. The approach was applied and validated in four disparate
datasets including a simulated population (5,100 individuals and 10,000 SNPs), a
highly structured experimental sheep population (1,421 individuals and 44,693
SNPs) and two large complex pedigree populations namely horse (1,077 individuals
and 38,124 SNPs) and cattle (2,457 individuals and 45,765 SNPs). In the simulated
and experimental sheep dataset, our method, which is unsupervised, successfully
identified all known key contributors. Applying our three-step approach to the
horse and cattle populations, we observed high-resolution population
substructures including the absence of obvious important key contributors.
Furthermore, we show that compared to commonly applied strategies to select
informative individuals for genotype imputation including the computation of
marginal gene contributions (Pedig) and the optimization of genetic relatedness
(Rel), the selection of key contributors provided the highest phasing accuracies
within the selected reference populations. The presented approach opens new
perspectives in the characterization and informed management of populations in
general, and in areas such as conservation genetics and selective animal breeding
in particular, where assessing the genetic contribution of influential and
admixed individuals is crucial for research and management applications. As such,
this method provides a valuable complement to common applied tools to visualize
complex population structures and to select individuals for re-sequencing.
PMID- 28520807
TI - Time from HIV diagnosis to commencement of antiretroviral therapy as an indicator
to supplement the HIV cascade: Dramatic fall from 2011 to 2015.
AB - INTRODUCTION: The HIV care cascade is increasingly used to evaluate HIV treatment
programs at the population level. However, the cascade indicators lack the
ability to show changes over time, which reduces their utility to guide health
policy. Alternatives have been proposed but are complex or result in a delay in
results. We propose a new indicator of ART uptake, the time from HIV diagnosis to
commencement of ART, and compare it to the existing cascade indicator of
proportion of patients on treatment and the WHO proposed cohort cascade indicator
of proportion of patients on treatment within one year of diagnosis. METHODS AND
MATERIALS: Records from patients from the two largest HIV treatment centres in
the state of Victoria, Australia (Melbourne Sexual Health Centre and The Alfred
Hospital Department of Infectious Diseases) from 2011 to 2015 were extracted. The
intervals between date of diagnosis, entry into care and initiation of ART were
compared. RESULTS AND DISCUSSION: From 2011 to 2015 the proportion of in-care
patients who were on ART rose from 87% to 93% (p<0.0001). From 2011 to 2014, the
proportion of patients in care and on ART within one year of diagnosis increased
from 43.4% to 78.9% (p = 0.001). The median time from diagnosis to ART fell from
418 days (IQR: 91-1176) to 77 days (IQR: 39-290)(p<0.001) by calendar year in
which ART was commenced. CONCLUSIONS: From 2011 to 2015 there were substantial
and clinically important falls in the median time from diagnosis to commencing
ART in those that commenced ART. The size of this dramatic change was not
apparent when only reporting the proportion of patients on ART. Time to ART is a
useful indicator and can be used to supplement existing cascade indicators in
measuring progress toward universal ART coverage.
PMID- 28520806
TI - ALS skeletal muscle shows enhanced TGF-beta signaling, fibrosis and induction of
fibro/adipogenic progenitor markers.
AB - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which
upper and lower motoneurons degenerate leading to muscle wasting, paralysis and
eventually death from respiratory failure. Several studies indicate that skeletal
muscle contributes to disease progression; however the molecular mechanisms
remain elusive. Fibrosis is a common feature in skeletal muscle under chronic
damage conditions such as those caused by muscular dystrophies or denervation.
However, the exact mechanisms of fibrosis induction and the cellular bases of
this pathological response are unknown. We show that extracellular matrix (ECM)
components are augmented in skeletal muscles of symptomatic hSOD1G93A mice, a
widely used murine model of ALS. These mice also show increased TGF-beta1 mRNA
levels, total Smad3 protein levels and p-Smad3 positive nuclei. Furthermore,
platelet-derived growth factor receptor-alpha (PDGFRalpha), Tcf4 and alpha-smooth
muscle actin (alpha-SMA) levels are augmented in the skeletal muscle of
symptomatic hSOD1G93A mice. Additionally, the fibro/adipogenic progenitors
(FAPs), which are the main producers of ECM constituents, are also increased in
these pathogenic conditions. Therefore, FAPs and ECM components are more abundant
in symptomatic stages of the disease than in pre-symptomatic stages. We present
evidence that fibrosis observed in skeletal muscle of symptomatic hSOD1G93A mice
is accompanied with an induction of TGF-beta signaling, and also that FAPs might
be involved in triggering a fibrotic response. Co-localization of p-Smad3
positive cells together with PDGFRalpha was observed in the interstitial cells of
skeletal muscles from symptomatic hSOD1G93A mice. Finally, the targeting of pro
fibrotic factors such as TGF-beta, CTGF/CCN2 and platelet-derived growth factor
(PDGF) signaling pathway might be a suitable therapeutic approach to improve
muscle function in several degenerative diseases.
PMID- 28520809
TI - Antenatal coffee and tea consumption and the effect on birth outcome and
hypertensive pregnancy disorders.
AB - BACKGROUND AND OBJECTIVE: Coffee and tea are commonly consumed during pregnancy.
While several of their components, like caffeine, have strong pharmacological
effects, the effect on the unborn fetus remains unclear. Caffeine intake has been
associated with abortion, preterm birth and fetal growth restriction, but a
general consensus on caffeine restriction is still lacking. We aimed to
investigate antenatal coffee, tea and caffeine consumption and the effect on
birth weight and length, gestational age at birth and hypertensive disorders in
pregnancy. METHODS: A total of 936 healthy pregnancies from the WHISTLER birth
cohort with data on coffee and tea consumption were included. Maternal and child
characteristics as well as antenatal coffee and tea consumption were obtained
through postpartum questionnaires. Reported consumption was validated using
available preconceptional data. Caffeine intake was calculated from coffee and
tea consumption. Linear and logistic regression was used to assess the
association with birth outcome and hypertensive disorders. RESULTS: After
adjustment for smoking and maternal age, a daily consumption of more than 300mg
of caffeine compared to less than 100mg of caffeine was significantly associated
with an increased gestational age (linear regression coefficient = 2.00 days,
95%CI = 0.12-4.21, P = 0.03). Tea consumption was significantly related to a
higher risk of pregnancy induced hypertension (OR = 1.13, 95%CI = 1.04-1.23, P =
0.004). No associations concerning coffee consumption or birth weight and birth
length were observed. CONCLUSIONS: Daily caffeine consumption of more than 300mg
is possibly associated with an increase in gestational age at birth. A possible
relation between high tea consumption and increased risk for pregnancy induced
hypertension warrants further research. For most outcomes, we found no
significant associations with coffee or tea intake.
PMID- 28520808
TI - Proteomic analysis of Biomphalaria glabrata plasma proteins with binding affinity
to those expressed by early developing larval Schistosoma mansoni.
AB - Interactions between early developing Schistosoma mansoni larval stages and the
hemolymph of its snail intermediate host represent the first molecular encounter
with the snail's immune system. To gain a more comprehensive understanding of
this early parasite-host interaction, biotinylated sporocyst tegumental membrane
(Mem) proteins and larval transformation proteins (LTP) were affixed to
streptavidin-agarose beads and used as affinity matrices to enrich for larval
reactive plasma proteins from susceptible (NMRI) and resistant (BS-90) strains of
the snail Biomphalaria glabrata. Nano-LC/MS-MS proteomic analyses of isolated
plasma proteins revealed a diverse array of 94 immune-and nonimmune-related
plasma proteins. Included among the immune-related subset were pattern
recognition receptors (lectins, LPS-binding protein, thioester-containing
proteins-TEPs), stress proteins (HSP60 and 70), adhesion proteins
(dermatopontins), metalloproteases (A Disintegrin And Metalloproteinase (ADAM),
ADAM-related Zn proteinases), cytotoxins (biomphalysin) and a Ca2+-binding
protein (neo-calmodulin). Variable immunoglobulin and lectin domain (VIgL) gene
family members, including fibrinogen-related proteins (FREPs), galectin-related
proteins (GREPs) and C-type lectin-related proteins (CREPs), were the most
prevalent of larval-reactive immune lectins present in plasma. FREPs were highly
represented, although only a subset of FREP subfamilies (FREP 2, 3 and 12) were
identified, suggesting potential selectivity in the repertoire of plasma lectins
recognizing larval glycoconjugates. Other larval-binding FREP-like and CREP-like
proteins possessing a C-terminal fibrinogen-related domain (FReD) or C-type
lectin binding domain, respectively, and an Ig-fold domain also were identified
as predicted proteins from the B. glabrata genome, although incomplete sequence
data precluded their placement into specific FREP/CREP subfamilies. Similarly, a
group of FReD-containing proteins (angiopoeitin-4, ficolin-2) that lacked N
terminal Ig-fold(s) were identified as a distinct group of FREP-like proteins,
separate from the VIgL lectin family. Finally, differential appearance of GREPs
in BS-90 plasma eluates, and others proteins exclusively found in eluates of the
NMRI strain, suggested snail strain differences in the expression of select
larval-reactive immune proteins. This hypothesis was supported by the finding
that differential gene expression of the GREP in BS-90 and ADAM in NMRI snail
strains generally correlated with their patterns of protein expression. In
summary, this study is the first to provide a global comparative proteomic
analysis of constitutively expressed plasma proteins from susceptible and
resistant B. glabrata strains capable of binding early-expressed larval S.
mansoni proteins. Identified proteins, especially those exhibiting differential
expression, may play a role in determining immune compatibility in this snail
host-parasite system. A complete listing of raw peptide data are available via
ProteomeXchange using identifier PXD004942.
PMID- 28520810
TI - Long chain saturated and unsaturated fatty acids exert opposing effects on
viability and function of GLP-1-producing cells: Mechanisms of lipotoxicity.
AB - BACKGROUND AND AIM: Fatty acids acutely stimulate GLP-1 secretion from L-cells in
vivo. However, a high fat diet has been shown to reduce the density of L-cells in
the mouse intestine and a positive correlation has been indicated between L-cell
number and GLP-1 secretion. Thus, the mechanism of fatty acid-stimulated GLP-1
secretion, potential effects of long-term exposure to elevated levels of
different fatty acid species, and underlying mechanisms are not fully understood.
In the present study, we sought to determine how long-term exposure to saturated
(16:0) and unsaturated (18:1) fatty acids, by direct effects on GLP-1-producing
cells, alter function and viability, and the underlying mechanisms. METHODS: GLP
1-secreting GLUTag cells were cultured in the presence/absence of saturated
(16:0) and unsaturated (18:1) fatty acids (0.125 mM for 48 h, followed by
analyses of viability and apoptosis, as well as involvement of fatty acid
oxidation, free fatty acid receptors (FFAR1) and ceramide synthesis. In addition,
effects on the expression of proglucagon, prohormone convertase 1/3 (PC1/3), free
fatty acid receptors (FFAR1, FFAR3), sodium glucose co-transporter (SGLT) and
subsequent secretory response were determined. RESULTS: Saturated (16:0) and
unsaturated (18:1) fatty acids exerted opposing effects on the induction of
apoptosis (1.4-fold increase in DNA fragmentation by palmitate and a 0.5-fold
reduction by oleate; p<0.01). Palmitate-induced apoptosis was associated with
increased ceramide content and co-incubation with Fumonisin B1 abolished this
lipo apoptosis. Oleate, on the other hand, reduced ceramide content, and-unlike
palmitate-upregulated FFAR1 and FFAR3, evoking a 2-fold increase in FFAR1
mediated GLP-1 secretion following acute exposure to 0.125 mmol/L palmitate;
(p<0.05). CONCLUSION/INTERPRETATION: Saturated (16:0), but not unsaturated
(18:1), fatty acids induce ceramide-mediated apoptosis of GLP-1-producing cells.
Further, unsaturated fatty acids confer lipoprotection, enhancing viability and
function of GLP-1-secreting cells. These data provide potential mechanistic
insight contributing to reduced L-cell mass following a high fat diet and
differential effects of saturated and unsaturated fatty acids on GLP-1 secretion
in vivo.
PMID- 28520812
TI - The effect of platelet-rich plasma on osseous healing in dogs undergoing high
tibial osteotomy.
AB - OBJECTIVES: The purpose of this study was to investigate whether platelet-rich
plasma (PRP) enhances osseous healing in conjunction with a high tibial osteotomy
in dogs. STUDY DESIGN: Randomized controlled trial. METHODS: Sixty-four client
owned pet dogs with naturally occurring rupture of the anterior cruciate ligament
and that were to be treated with a high tibial osteotomy (tibial plateau leveling
osteotomy) were randomized into the treatment or control group. Dogs in the
treatment group received autologous platelet-rich plasma activated with calcium
chloride and bovine thrombin to produce a well-formed PRP gel that was placed
into the osteotomy at the time of surgery. Dogs in the control group received
saline lavage of the osteotomy. All dogs had the osteotomy stabilized with
identical titanium alloy implants and all aspects of the surgical procedure and
post-operative care were identical among dogs of the two groups. Bone healing was
assessed at exactly 28, 49, and 70 days after surgery with radiography and
ultrasonography and with MRI at day 28. The effect of PRP on bone healing was
assessed using a repeated measures analysis of covariance with radiographic and
ultrasonographic data and using a t-test with the MRI data. RESULTS: Sixty dogs
completed the study. There were no significant differences in age, weight, or
gender distribution between the treatment and control groups. Twenty-seven dogs
were treated with PRP and 33 were in the control group. The average platelet
concentration of the PRP was 1.37x106 platelets/MUL (+/-489x103) with a leukocyte
concentration of 5.45x103/MUL (+/-3.5x103). All dogs demonstrated progressive
healing over time and achieved clinically successful outcomes. Time since surgery
and patient age were significant predictors of radiographic healing and time
since surgery was a significant predictor of ultrasonographic assessment of
healing. There was no significant effect of PRP treatment as assessed
radiographically, ultrasonographically, or with MRI. CONCLUSION: The PRP used in
this study did not hasten osseous union in dogs treated with a high tibial
osteotomy.
PMID- 28520811
TI - Body shape index: Sex-specific differences in predictive power for all-cause
mortality in the Japanese population.
AB - BACKGROUND: While body mass index (BMI) is the most widely used anthropometric
measure, its association with all-cause mortality is generally J-shaped or U
shaped. A body shape index (ABSI) is a recently formulated anthropometric measure
that shows linear relationship to all-cause mortality, especially in Caucasian
cohorts. We aimed to address the relationship between ABSI and all-cause
mortality in Asians and to assess the influence of sex difference and of chronic
kidney disease (CKD) on this relationship. METHODS: This was a longitudinal
cohort study assessing the association of ABSI, BMI, waist circumference (WC),
and waist-to-height ratio (WHtR) with all-cause mortality in a Japanese
nationwide Specific Health Checkup database. The study enrolled 160,625
participants followed-up between 2008 and 2012. We calculated the all-cause
mortality risk associated with a 1-standard deviation increase (+1SD) in ABSI,
BMI, WC, or WHtR in cohorts stratified by sex and the presence of CKD. RESULTS:
During the 4-year follow up, 1.3% of participants died. In men, ABSI (+1SD)
significantly increased the risk for all-cause mortality after adjusting for
other known risk factors including CKD; hazard ratio (HR) and 95% confidence
intervals (CI) of non-CKD cohort, 1.30 (1.18 to 1.43), p<0.01; HR and 95%CI of
CKD cohort, 1.16 (1.01 to 1.34), p = 0.04. In women, ABSI (+1SD) did not show
significant association with all-cause mortality, especially in the CKD cohort;
HR and 95% CI of non-CKD cohort, 1.07 (0.99 to 1.17), p = 0.09; HR and 95%CI of
CKD cohort, 0.98 (0.84 to 1.14), p = 0.78. Conversely, BMI (+1SD) was associated
with significantly lower risk in men, although minimal association was found in
women. WC and WHtR showed little association with all-cause mortality. On
stratification per ABSI quartiles, mortality risk increased linearly and
significantly with ABSI in men, but not in women with CKD. Both BMI and WC showed
significant but U-shaped association with mortality in the non-CKD cohort and in
men with CKD. WHtR also showed significant U-shaped association with mortality in
men. CONCLUSIONS: In the Japanese population, ABSI showed significant and linear
correlation with mortality risk in men but not in women, especially in the
presence of CKD.
PMID- 28520813
TI - Pancreatic fat content by magnetic resonance imaging in subjects with
prediabetes, diabetes, and controls from a general population without
cardiovascular disease.
AB - BACKGROUND/OBJECTIVE: Despite the relevance of pancreatic fat content in the
development of metabolic diseases, its association with impaired glucose
metabolism, diabetes, and other adipose tissue compartments remains unclear.
Thus, we determined differences in pancreatic fat content by magnetic resonance
imaging (MRI) between subjects with prediabetes, diabetes, and normal controls in
a cohort from the general population. METHODS: Subjects without history of
cardiovascular disease with established diabetes or prediabetes as well as normal
controls were included and underwent whole-body MRI on a 3T scanner. Pancreatic
fat content was quantified by measuring the proton-density fat fraction
(PDFFpanc) using a 3D multi-echo GRE sequence (increment: 1.23 ms, 6 echoes) by
placing ROIs in the pancreatic head, body, and tail by independent readers. In
addition, hepatic fat content as well as abdominal subcutaneous and visceral
adipose tissue (SAT and VAT) were measured by multi-echo GRE and 3D 2-point
volume-interpolated DIXON MRI, respectively. Univariate and multivariate analyses
were employed to determine associations. RESULTS: A total of 385 subjects were
included in the analysis (median age: 57 years, 58.2% males), of them 53 were
classified as subjects with diabetes, 95 as prediabetes, and 237 as controls
(13.8%, 24.7%, and 61.6%; respectively). The median PDFFpanc was 5.2% [IQR 3.3
9.4], and significantly higher in subjects with prediabetes and diabetes as
compared to controls (PDFFpanc: 6.2% [IQR: 3.5-12] vs. 8.6% [IQR: 4.3-17.5] vs.
4.9% [3.1-7.4], p<0.001, respectively). After adjusting for age, gender and BMI
the association was attenuated (all p>0.12). While in univariate analysis BMI,
PDFFhepatic, SAT and VAT were associated with PDFFpanc (all p<0.05), only VAT
predicted PDFFpanc independently (beta: 0.02, 95%-confidence interval: 0.01-0.04,
p<0.001). CONCLUSION: While pancreatic fat content differs significantly between
subjects with prediabetes, diabetes and controls, this association may be
confounded by age, gender, and the amount of VAT in this cross-sectional study.
PMID- 28520814
TI - Rs12970134 near MC4R is associated with appetite and beverage intake in
overweight and obese children: A family-based association study in Chinese
population.
AB - BACKGROUND: Recent studies indicated that eating behaviors are under genetic
influence, and the melanocortin 4 receptor (MC4R) gene polymorphisms can affect
the total energy intake and the consumption of fat, protein and carbohydrates.
Our study aims at investigating the association of the MC4R polymorphism with
appetite and food intake among Chinese children. METHODS: A family-based
association study was conducted among 151 Chinese trios whose offsprings were
overweight/obese children aged 9-15 years. The rs12970134 near MC4R was
genotyped, and the Children Eating Behavior Questionnaire (CEBQ) and a self
designed questionnaire measuring food intake were performed. The FBAT and PBAT
software packages were used. RESULTS: The family-based association analysis
showed that there was a significant association between rs12970134 and obesity (Z
= 2.449, P = 0.014). After adjusting for age, gender and standardized BMI,
rs12970134 was significantly associated with food responsiveness (FR) among
children (beta'b = 0.077, Pb = 0.028), and with satiety responsiveness (SR) in
trios (P = -0.026). The polymorphism was associated with beverage intake (beta'b
= 0.331, Pb = 0.00016 in children; P = 0.043 in trios), but not significantly
associated with vegetable, fruit or meat intake (P>0.050). We further found a
significant mediation effect among the rs12970134, FR and beverage intake (b =
0.177, P = 0.047). CONCLUSIONS: Our study is the first to report that rs12970134
near MC4R was associated with appetite and beverage intake, and food
responsiveness could mediate the effect of rs12970134 on beverage intake in
overweight and obese Chinese children population. Further studies are needed to
uncover the genetic basis for eating behaviors, which could lead to develop and
implement effective interventional strategies early in life.
PMID- 28520815
TI - Metabolic profiling by gas chromatography-mass spectrometry of energy metabolism
in high-fat diet-fed obese mice.
AB - A novel, selective and sensitive single-ion monitoring (SIM) gas chromatography
mass spectrometry (GCMS) method was developed and validated for the determination
of energy metabolites related to glycolysis, the tricarboxylic acid (TCA) cycle,
glutaminolysis, and fatty acid beta-oxidation. This assay used N-tert
butyldimethylsilyl-N-methyltrifluoroacetamide (MTBSTFA) containing 1% tert
butyldimethylchlorosilane (TBDMCS) as derivatizing reagent and was highly
reproducible, sensitive, specific and robust. The assay was used to analyze liver
tissue and serum from C57BL/6N obese mice fed a high-fat diet (HFD) and C57BL/6N
mice fed normal chow for 8 weeks. HFD-fed mice serum displayed statistically
significantly reduced concentrations of pyruvate, citrate, succinate, fumarate,
and 2-oxoglutarate, with an elevated concentration of pantothenic acid. In liver
tissue, HFD-fed mice exhibited depressed levels of glycolysis end-products
pyruvate and lactate, glutamate, and the TCA cycle intermediates citrate,
succinate, fumarate, malate, and oxaloacetate. Pantothenate levels were 3-fold
elevated accompanied by a modest increased gene expression of Scl5a6 that encodes
the pantothenate transporter SLC5A6. Since both glucose and fatty acids inhibit
coenzyme A synthesis from pantothenate, it was concluded that these data were
consistent with downregulated fatty acid beta-oxidation, glutaminolysis,
glycolysis, and TCA cycle activity, due to impaired anaplerosis. The novel SIM
GCMS assay provided new insights into metabolic effects of HFD in mice.
PMID- 28520817
TI - Heat in the southeastern United States: Characteristics, trends, and potential
health impact.
AB - High summer temperatures in extratropical areas have an impact on the public's
health, mainly through heat stress, high air pollution concentrations, and the
transmission of tropical diseases. The purpose of this study is to examine the
current characteristics of heat events and future projections of summer apparent
temperature (AT)-and associated health concerns-throughout the southeastern
United States. Synoptic climatology was used to assess the atmospheric
characteristics of extreme heat days (EHDs) from 1979-2015. Ozone concentrations
also were examined during EHDs. Trends in summer-season AT over the 37-year
period and correlations between AT and atmospheric circulation were determined.
Mid-century estimates of summer AT were calculated using downscaled data from an
ensemble of global climate models. EHDs throughout the Southeast were
characterized by ridging and anticyclones over the Southeast and the presence of
moist tropical air masses. Exceedingly high ozone concentrations occurred on EHDs
in the Atlanta area and throughout central North Carolina. While summer ATs did
not increase significantly from 1979-2015, summer ATs are projected to increase
substantially by mid-century, with most the Southeast having ATs similar to that
of present-day southern Florida (i.e., a tropical climate). High ozone
concentrations should continue to occur during future heat events. Large urban
areas are expected to be the most affected by the future warming, resulting from
intensifying and expanding urban heat islands, a large increase in heat
vulnerable populations, and climate conditions that will be highly suitable for
tropical-disease transmission by the Aedes aegypti mosquito. This nexus of
vulnerability creates the potential for heat-related morbidity and mortality, as
well as the appearance of disease not previously seen in the region. These
effects can be attenuated by policies that reduce urban heat (e.g., cool roofs
and green roofs) and that improve infrastructure (e.g. emergency services,
conditioned space).
PMID- 28520816
TI - High prevalence of elevated blood lead levels in both rural and urban Iowa
newborns: Spatial patterns and area-level covariates.
AB - Lead in maternal blood can cross the placenta and result in elevated blood lead
levels in newborns, potentially producing negative effects on neurocognitive
function, particularly if combined with childhood lead exposure. Little research
exists, however, into the burden of elevated blood lead levels in newborns, or
the places and populations in which elevated lead levels are observed in
newborns, particularly in rural settings. Using ~2300 dried bloods spots
collected within 1-3 days of birth among Iowa newborns, linked with the area of
mother's residence at the time of birth, we examine the spatial patterns of
elevated (>5 MUg/dL) blood lead levels and the ecological-level predictors of
elevated blood lead levels. We find that one in five newborns exceed the 5 MUg/dL
action level set by the US Centers for Disease Control & Prevention (CDC).
Bayesian spatial zero inflated regression indicates that elevated blood lead in
newborns is associated with areas of increased pre-1940s housing and childbearing
age women with low educational status in both rural and urban settings. No
differences in blood lead levels or the proportion of children exceeding 5 MUg/dL
are observed between urban and rural maternal residence, though a spatial cluster
of elevated blood lead is observed in rural counties. These characteristics can
guide the recommendation for testing of infants at well-baby appointments in
places where risk factors are present, potentially leading to earlier initiation
of case management. The findings also suggest that rural populations are at as
great of risk of elevated blood lead levels as are urban populations. Analysis of
newborn dried blood spots is an important tool for lead poisoning surveillance in
newborns and can direct public health efforts towards specific places and
populations where lead testing and case management will have the greatest impact.
PMID- 28520818
TI - Evaluation of a real-time method of simultaneous amplification and testing in
diagnosis of Mycoplasma pneumoniae infection in children with pneumonia.
AB - Mycoplasma pneumoniae (M. pneumoniae) infection can cause community acquired
pneumonia in children. A real-time method of simultaneous amplification and
testing of M. pneumoniae (SAT-MP) was developed to diagnose M. pneumoniae
targeting a region of the ribosomal RNA. The SAT-MP assay can accurately identify
M. pneumoniae with a detection range from 101 to 107 CFU/ml. In this study, the
specimens from 315 children with pneumonia were collected and analyzed by SAT-MP
in parallel with real-time PCR method and IgM ELISA assay. The positive rates of
these specimens examined by SAT-MP assay, real-time PCR method and IgM ELISA
assay were 16.51%, 15.56% and 12.70% respectively. While there was statistical
significance (p = 0.04) between SAT-MP assay and IgM ELISA assay, no statistical
significance (p = 0.25) was found between SAT-MP assay and real-time PCR method
and these two methods had high consistency (kappa value = 0.97). These findings
indicate that the newly developed SAT-MP assay is a rapid, sensitive and specific
method for identifying M. pneumoniae with potential clinical application in the
early diagnosis of M. pneumoniae infection.
PMID- 28520820
TI - Association between features of patient-provider discussions and routine prostate
specific antigen testing.
AB - INTRODUCTION: Although the US Preventive Services Task Force recommends against
routine prostate cancer screening with prostate-specific antigen (PSA) testing,
specialty organizations support screening via shared decision making between
providers and selected patients. While discussions about advantages and
disadvantages of testing are a feature of patient-centered care, it is unclear
how provider recommendations and the presence of a personal doctor influence
testing in the presence of such discussions. MATERIALS AND METHODS: We used the
2013 Behavioral Risk Factor Surveillance System to identify 1,737 male
respondents surveyed about their PSA testing decisions. We describe the
prevalence of provider recommendations and utilize weighted multivariable
logistic regression models to examine the impact of provider recommendations and
presence of a personal doctor on routine testing while accounting for patient
provider discussions about advantages and disadvantages. RESULTS: The majority
(70.4%) of respondents reported some form of discussion with providers about
testing and most underwent screening in accordance with provider recommendations.
In multivariable analyses, men whose providers had never recommended PSA test
were less likely to receive screening [OR 0.03, 95% CI (0.02-0.05)], and patients
who did not identify a personal doctor in their care were less likely to undergo
testing [OR 0.12, 95% CI (0.04-0.32)]. DISCUSSION: Provider recommendations and
having a personal doctor are associated with routine PSA testing. These findings
suggest that providers and policymakers should be aware of how the content and
context of communication with patients, beyond discussions of risks and benefits,
can influence routine PSA testing behaviors.
PMID- 28520819
TI - In vitro analysis of the segmental flexibility of the thoracic spine.
AB - Basic knowledge about the thoracic spinal flexibility is limited and to the
authors' knowledge, no in vitro studies have examined the flexibility of every
thoracic spinal segment under standardized experimental conditions using pure
moments. In our in vitro study, 68 human thoracic functional spinal units
including the costovertebral joints (at least n = 6 functional spinal units per
segment from T1-T2 to T11-T12) were loaded with pure moments of +/-7.5 Nm in
flexion/extension, lateral bending, and axial rotation in a custom-built spine
tester to analyze range of motion (ROM) and neutral zone (NZ). ROM and NZ showed
symmetric motion behavior in all loading planes. In each loading direction, the
segment T1-T2 exhibited the highest ROM. In flexion/extension, the whole thoracic
region, with exception of T1-T2 (14 degrees ), had an average ROM between 6
degrees and 8 degrees . In lateral bending, the upper thoracic region (T1-T7)
was, with an average ROM between 10 degrees and 12 degrees , more flexible than
the lower thoracic region (T7-T12) with an average ROM between 8 degrees and 9
degrees . In axial rotation, the thoracic region offered the highest overall
flexibility with an average ROM between 10 degrees and 12 degrees in the upper
and middle thoracic spine (T1-T10) and between 7 degrees and 8 degrees in the
lower thoracic spine (T10-T12), while a trend of continuous decrease of ROM could
be observed in the lower thoracic region (T7-T12). Comparing these ROM values
with those in literature, they agree that ROM is lowest in flexion/extension and
highest in axial rotation, as well as decreasing in the lower segments in axial
rotation. Differences were found in flexion/extension and lateral bending in the
lower segments, where, in contrast to the literature, no increase of the ROM from
superior to inferior segments was found. The data of this in vitro study could be
used for the validation of numerical models and the design of further in vitro
studies of the thoracic spine without the rib cage, the verification of animal
models, as well as the interpretation of already published human in vitro data.
PMID- 28520822
TI - Correction: Biochemical evaluation of the anticancer potential of the polyamine
based nanocarrier Nano11047.
AB - [This corrects the article DOI: 10.1371/journal.pone.0175917.].
PMID- 28520824
TI - Expanding Purpura in a Neutropenic Patient.
PMID- 28520821
TI - The percentage of Epidermal Growth Factor Receptor (EGFR)-mutated neoplastic
cells correlates to response to tyrosine kinase inhibitors in lung
adenocarcinoma.
AB - BACKGROUND: Epidermal Growth Factor Receptor (EGFR) molecular analysis is
performed to assess the responsiveness to Tyrosine Kinase Inhibitors (TKIs) in
patients with Non-Small Cell Lung Cancer (NSCLC). The existence of molecular
intra-tumoral heterogeneity has been observed in lung cancers. The aim of the
present study is to investigate if the percentage of mutated neoplastic cells
within the tumor sample might influence the responsiveness to TKIs treatment.
MATERIAL AND METHODS: A total of 931 cases of NSCLC were analyzed for EGFR
mutational status (exon 18, 19, 20, 21) using Next Generation Sequencer. The
percentage of mutated neoplastic cells was calculated after normalizing the
percentage of mutated alleles obtained after next generation sequencer analysis
with the percentage of neoplastic cells in each tumor. RESULTS: Next generation
sequencing revealed an EGFR mutation in 167 samples (17.9%), mainly deletions in
exon 19. In 18 patients treated with TKIs and with available follow-up, there was
a significant correlation between the percentage of mutated neoplastic cells and
the clinical response (P = 0.017). Patients with a percentage of mutated
neoplastic cells greater than 56%, have a statistical trend (P = 0.081) for
higher Overall Survival (26.3 months) when compared to those with a rate of
mutated neoplastic cells lower than 56% (8.2 months). CONCLUSIONS: The percentage
of EGFR-mutated neoplastic cells in the tumor is associated with response to
TKIs. A "quantitative result" of EGFR mutational status might provide useful
information in order to recognize those patients which might have the greatest
benefit from TKIs.
PMID- 28520825
TI - Toward Palliative Care for All Patients With Advanced Cancer.
PMID- 28520823
TI - Comparison of Tunnel and Crestal Incision Techniques in Reconstruction of
Localized Alveolar Defects.
AB - PURPOSE: The aim of this study was to compare the complication rates of recipient
sites prepared using two incision techniques: crestal and tunnel. MATERIALS AND
METHODS: In this prospective study, patients underwent augmentation procedures
(68 patients; 75 sites) by the same surgeon that were performed consecutively
using the crestal incision technique (27 horizontal, 10 vertical; crestal group)
or the tunnel incision technique (27 horizontal, 11 vertical; tunnel group).
Autogenous bone block grafts were harvested with a piezoelectric surgical device,
and the grafts were fixed at the recipient sites by two titanium screws in both
groups. The authors evaluated minor exposure, transient paresthesia, major
exposure, permanent paresthesia, gingival recession at adjacent teeth, surgery
time, and visual analog scale pain scores. RESULTS: Soft tissue dehiscence and
graft failure were significantly lower in patients undergoing the tunnel
technique. CONCLUSION: The tunnel incision technique significantly decreased soft
tissue exposure, the most common complication of augmentation procedures with
autogenous onlay bone grafts. This technique should be considered an alternative
to the crestal incision technique for preparation of the recipient site.
PMID- 28520826
TI - Current Challenges Associated With Next-Generation Sequencing of Breast Cancer
Reply.
PMID- 28520827
TI - Surgical Outcomes of Bony Batten Grafting to Correct Caudal Septal Deviation in
Septoplasty.
AB - Improtance: Correction of caudal septal deviation with a batten graft has been
popularized recently. However, few reports have documented the surgical outcomes
of this technique, especially the use of bony batten grafts in septoplasty.
Objective: To evaluate the surgical outcomes of bony batten grafting for the
management of caudal septal deviation in endonasal septoplasty. Design, Setting,
and Participants: This retrospective cohort study evaluates the medical records
of 141 patients with caudal septal deviation who underwent septoplasty using bony
batten grafts from September 1, 2011, through February 29, 2016, at a tertiary
referral hospital. Patients were divided into primary and secondary surgery
groups. Patients were also divided into the septoplasty plus turbinate surgery
and the septoplasty only group. Endoscopic assessment of deviation correction was
performed, and postoperative complications were analyzed. Main Outcomes and
Measures: Patient satisfaction and symptom improvement were evaluated via
telephone interviews by using the Nasal Obstruction Symptoms Evaluation (NOSE)
scores. Results: Of the 141 patients (24 women [17%] and 117 men [83%]; mean [SD]
age, 32.8 [12.9] years), 86 (61%) rated their symptoms in the postoperative
survey as much improved; 50 (35.5%), improved; 4 (2.8%), no change; and 1 (0.7%),
worse. All patients had significantly improved mean (SD) postoperative NOSE
scores (28.7 [22.0]; 95% CI, 25.0-32.4) compared with preoperative scores (70.5
[26.7]; 95% CI, 66.0-75.0; P < .001). No significant intergroup differences were
observed in surgical outcome between the 116 patients undergoing primary surgery
(mean [SD] NOSE score, 28.2 [21.9]) and 25 undergoing secondary surgery (mean
[SD] NOSE score, 30.8 [24.3]; P = .34). No significant difference in surgical
outcome was found between the 102 patients in the turbinate surgery group (mean
[SD] NOSE score, 28.1 [20.8]) and 39 in the septoplasty only group (mean [SD]
NOSE score, 30.4 [23.7]; P = .65). On endoscopic examination for surgical
outcome, 128 patients (90.8%) had a straight septum and 13 (9.2%) had improved
but residual caudal deviation. Postoperative complications included septal
hematoma in 4 patients, hyposmia in 2, and chondritis in 1; all patients were
treated successfully. Four patients required revision surgery because of
incomplete functional correction or a desire for rhinoplasty. Conclusions and
Relevance: Septoplasty using bony batten grafts is useful for correcting caudal
septal deviation with favorable surgical outcomes and an acceptable complication
rate. Level of Evidence: 3.
PMID- 28520828
TI - Targeted Therapy as an Alternative to Whole-Brain Radiotherapy in EGFR-Mutant or
ALK-Positive Non-Small-Cell Lung Cancer With Brain Metastases.
AB - Clinical Question: Is up-front whole-brain radiotherapy required to treat
multiple brain metastases from non-small-cell lung cancer when highly active
targeted therapies are available? Clinical Application: Patients with EGFR-mutant
or ALK-positive non-small-cell lung cancer with brain metastases now have the
potential to achieve a prolonged survival. Through use of highly active targeted
therapies, whole-brain radiotherapy can be safely postponed, diminishing toxic
effects that could impair quality of life.
PMID- 28520830
TI - Diffuse Parotid Swelling From an Underlying Parotid Mass in a Pediatric Patient.
PMID- 28520831
TI - Current Challenges Associated With Next-Generation Sequencing of Breast Cancer.
PMID- 28520832
TI - Evaluation of Monitored Anesthesia Care in Sialendoscopy.
AB - Importance: In the United States, sialendoscopy is most often performed under
general anesthesia with endotracheal intubation (GETA); however, monitored
anesthesia care (MAC) may be a viable alternative. Objective: To investigate
patient characteristics and outcomes following sialendoscopy performed under MAC
or GETA to assess the potential of MAC as an alternative anesthetic option.
Design, Setting, and Participants: A retrospective review of medical records on
patients who underwent sialendoscopy between October 1, 2011, and August 31,
2014, was performed. Patient characteristics, salivary stone characteristics,
intraoperative findings, operative time (OT), anesthesia time (AT), and outcomes
were evaluated. Data analysis was performed from November 1, 2015, to March 1,
2016. Main Outcomes and Measures: Operative and anesthetic times for
sialendoscopy under MAC and GETA. Results: Sixty-five patients underwent 70
sialendoscopy procedures: 27 performed under MAC, 43 under GETA. Overall, 37 of
65 (56.9%) patients were women, with 17 (63.0%) in the MAC group and 20 (52.6%)
in the GETA group. Mean (SD) patient age was 49.4 (17.3) and 47.2 (16.2) years
for the MAC and GETA cohorts, respectively. Median (25th-75th quartiles) OT in
minutes for MAC cases was significant for no stones (49.0 [31.0-49.0]) and stones
(41.0 [28.0-92.0]) present; nonsignificant findings were stones in the Wharton
(46.0 [28.0-92.0]) and Stenson (37.0; 1 case) ducts. For GETA cases, significance
was also demonstrated for no stones (55.0 [52.0-91.0]) and stones (77.0 [56.0
107.0]) present; nonsignificant findings were stones in the Wharton (79.0 [56.0
107.0]) and Stenson (65.0 [49.0-98.0]) ducts. The AT in minutes for MAC cases was
significant for no stones (33.0 [30.0-39.0]) and stones (38.0 [32.0-55.0])
present; nonsignificant findings were stones in the Wharton (60.0 [32.0-55.0])
and Stenson (37.0; 1 case) ducts. For GETA cases, findings were also significant
for no stones (61.0 [52.0-67.0]) and stones (59.0 [53.0-67.0]) present;
nonsignificant findings were stones in the Wharton (60.0 [54.0-69.0]) and Stenson
(52.0 [48.0-61.0]) ducts. Conclusions and Relevance: This study suggests that
sialendoscopy under MAC has faster median OT and AT, regardless of varying case
circumstances, such as the presence or lack of stones, successful stone removal,
stone size (>5 mm), stone location, and sialendoscopy-assisted open procedures.
Sialendoscopy under MAC may be a reasonable anesthetic alternative to GETA in an
appropriate setting with an experienced surgeon, experienced anesthesiologist
comfortable with administering MAC, cases with small (<4-mm) singular stones, and
patients comfortable with undergoing the procedure without GETA.
PMID- 28520829
TI - Association Between Combined TMPRSS2:ERG and PCA3 RNA Urinary Testing and
Detection of Aggressive Prostate Cancer.
AB - Importance: Potential survival benefits from treating aggressive (Gleason score,
>=7) early-stage prostate cancer are undermined by harms from unnecessary
prostate biopsy and overdiagnosis of indolent disease. Objective: To evaluate the
a priori primary hypothesis that combined measurement of PCA3 and TMPRSS2:ERG
(T2:ERG) RNA in the urine after digital rectal examination would improve
specificity over measurement of prostate-specific antigen alone for detecting
cancer with Gleason score of 7 or higher. As a secondary objective, to evaluate
the potential effect of such urine RNA testing on health care costs. Design,
Setting, and Participants: Prospective, multicenter diagnostic evaluation and
validation in academic and community-based ambulatory urology clinics.
Participants were a referred sample of men presenting for first-time prostate
biopsy without preexisting prostate cancer: 516 eligible participants from among
748 prospective cohort participants in the developmental cohort and 561 eligible
participants from 928 in the validation cohort. Interventions/Exposures: Urinary
PCA3 and T2:ERG RNA measurement before prostate biopsy. Main Outcomes and
Measures: Presence of prostate cancer having Gleason score of 7 or higher on
prostate biopsy. Pathology testing was blinded to urine assay results. In the
developmental cohort, a multiplex decision algorithm was constructed using urine
RNA assays to optimize specificity while maintaining 95% sensitivity for
predicting aggressive prostate cancer at initial biopsy. Findings were validated
in a separate multicenter cohort via prespecified analysis, blinded per
prospective-specimen-collection, retrospective-blinded-evaluation (PRoBE)
criteria. Cost effects of the urinary testing strategy were evaluated by modeling
observed biopsy results and previously reported treatment outcomes. Results:
Among the 516 men in the developmental cohort (mean age, 62 years; range, 33-85
years) combining testing of urinary T2:ERG and PCA3 at thresholds that preserved
95% sensitivity for detecting aggressive prostate cancer improved specificity
from 18% to 39%. Among the 561 men in the validation cohort (mean age, 62 years;
range, 27-86 years), analysis confirmed improvement in specificity (from 17% to
33%; lower bound of 1-sided 95% CI, 0.73%; prespecified 1-sided P = .04), while
high sensitivity (93%) was preserved for aggressive prostate cancer detection.
Forty-two percent of unnecessary prostate biopsies would have been averted by
using the urine assay results to select men for biopsy. Cost analysis suggested
that this urinary testing algorithm to restrict prostate biopsy has greater
potential cost-benefit in younger men. Conclusions and Relevance: Combined
urinary testing for T2:ERG and PCA3 can avert unnecessary biopsy while retaining
robust sensitivity for detecting aggressive prostate cancer with consequent
potential health care cost savings.
PMID- 28520834
TI - Effect of Electrode Montage and Head Position on Air-Conducted Ocular Vestibular
Evoked Myogenic Potential.
AB - Purpose: The purpose of this investigation was to identify the optimal recording
parameters for evoking the ocular vestibular evoked myogenic potential (oVEMP)
using air-conduction stimuli. Method: Subjects were 17 otologically and
neurologically intact adults (age: M = 24.18 years, SD = 1.91 years). The oVEMP
responses were elicited using a 500-Hz tone burst air-conduction stimulus
presented at an intensity of 95 dB nHL. The setting was a balance function
laboratory that was part of a large tertiary care otology clinic. Results: The
oVEMP electrode montage and body position that yielded the largest oVEMP
amplitude was the belly-tendon montage (Sandhu, George, & Rea, 2013), recorded
with the subject in the sitting position. The N1 latency recorded with the belly
tendon montage was significantly shorter than that recorded for the infraorbital
montage in both the sitting and supine positions. Conclusion: The belly-tendon
recording montage with the subject sitting yields significantly larger oVEMP
amplitudes and shorter N1 latencies than do traditional bipolar infraorbital
recordings.
PMID- 28520836
TI - Can Population-Based Epidemiologic Studies Still Contribute to the Dialogue on
Eye Research?
PMID- 28520835
TI - Primary Care of Patients With Chronic Pain.
PMID- 28520833
TI - Evaluation of Diabetic Retinal Screening and Factors for Ophthalmology Referral
in a Telemedicine Network.
AB - Importance: Retinal telescreening for evaluation of diabetic retinopathy (DR) in
the primary care setting may be useful in reaching rural and underserved
patients. Objectives: To evaluate telemedicine retinal screenings for patients
with type 1 or 2 diabetes and identify factors for ophthalmology referral in the
North Carolina Diabetic Retinopathy Telemedicine Network. Design, Setting, and
Participants: A preimplementation and postimplementation evaluation was conducted
from January 6, 2014, to November 1, 2015, at 5 primary care clinics serving
rural and underserved populations in North Carolina among 1787 adult patients
with type 1 or 2 diabetes who received primary care at the clinics and obtained
retinal telescreening to determine the presence and severity of DR. A total of
1661 patients with complete data were included in the statistical analysis.
Intervention: Nonmydriatic fundus photography with remote interpretation by an
expert. Main Outcomes and Measures: Number of patients recruited, level of
detected DR, change in rates of screening, rate of ophthalmology referral,
percentage of completed referrals, and patient characteristics associated with
varying levels of DR. Results: Of the 1661 patients (1041 women and 620 men; mean
[SD] age, 55.4 [12.7] years), 1323 patients (79.7%) had no DR, 183 patients
(11.0%) had DR without a need for an ophthalmology referral, and 155 patients
(9.3%) had DR with a need for an ophthalmology referral. The mean rate of
screening for DR before implementation of the program was 25.6% (1512 of 5905),
which increased to 40.4% (1884 of 4664) after implementation. A total of 93
referred patients (60.0%) completed an ophthalmology referral visit within the
study period. Older patients (odds ratio [OR], 1.28; 95% CI, 1.11-1.48) and
African American patients (OR, 1.84; 95% CI, 1.24-2.73) or other racial/ethnic
minorities (OR, 2.19; 95% CI, 1.16-4.11) had greater odds of requiring an
ophthalmology referral compared with white and/or younger patients. Patients with
higher hemoglobin A1c levels (OR, 1.19 per unit change; 95% CI, 1.13-1.25 per
unit change) and longer duration of diabetes (OR, 1.76 per decade; 95% CI, 1.53
2.02 per decade) had greater odds of DR requiring an ophthalmology referral.
History of stroke (OR, 1.65; 95% CI, 1.10-2.48) and kidney disease (OR, 1.59; 95%
CI, 1.10-2.31) were strongly associated with DR and ophthalmology referral.
Conclusions and Relevance: When implemented in the primary care setting, retinal
telescreening increased the rate of evaluation for DR for patients in rural and
underserved settings. This strategy may also increase access to care for
minorities and patients with DR requiring treatment.
PMID- 28520837
TI - Enlarging Orbital Mass in a Previously Healthy Man.
PMID- 28520839
TI - Glaucoma, Cognitive Decline, and Healthy Aging.
PMID- 28520838
TI - Effect of the PREPARE Website vs an Easy-to-Read Advance Directive on Advance
Care Planning Documentation and Engagement Among Veterans: A Randomized Clinical
Trial.
AB - Importance: Documentation rates of patients' medical wishes are often low. It is
unknown whether easy-to-use, patient-facing advance care planning (ACP)
interventions can overcome barriers to planning in busy primary care settings.
Objective: To compare the efficacy of an interactive, patient-centered ACP
website (PREPARE) with an easy-to-read advance directive (AD) to increase
planning documentation. Design, Setting, and Participants: This was a comparative
effectiveness randomized clinical trial from April 2013 to July 2016 conducted at
multiple primary care clinics at the San Francisco VA Medical Center. Inclusion
criteria were age of a least 60 years; at least 2 chronic and/or serious
conditions; and 2 or more primary care visits; and 2 or more additional clinic,
hospital, or emergency room visits in the last year. Interventions: Participants
were randomized to review PREPARE plus an easy-to-read AD or the AD alone. There
were no clinician and/or system-level interventions or education. Research staff
were blinded for all follow-up measurements. Main Outcomes and Measures: The
primary outcome was new ACP documentation (ie, legal forms and/or discussions) at
9 months. Secondary outcomes included patient-reported ACP engagement at 1 week,
3 months, and 6 months using validated surveys of behavior change process
measures (ie, 5-point knowledge, self-efficacy, readiness scales) and action
measures (eg, surrogate designation, using a 0-25 scale). We used intention-to
treat, mixed-effects logistic and linear regression, controlling for time, health
literacy, race/ethnicity, baseline ACP, and clustering by physician. Results: The
mean (SD) age of 414 participants was 71 (8) years, 38 (9%) were women, 83 (20%)
had limited literacy, and 179 (43%) were nonwhite. No participant characteristic
differed significantly among study arms at baseline. Retention at 6 months was
90%. Advance care planning documentation 6 months after enrollment was higher in
the PREPARE arm vs the AD-alone arm (adjusted 35% vs 25%; odds ratio, 1.61 [95%
CI, 1.03-2.51]; P = .04). PREPARE also resulted in higher self-reported ACP
engagement at each follow-up, including higher process and action scores; P <.001
at each follow-up). Conclusions and Relevance: Easy-to-use, patient-facing ACP
tools, without clinician- and/or system-level interventions, can increase
planning documentation 25% to 35%. Combining the PREPARE website with an easy-to
read AD resulted in higher planning documentation than the AD alone, suggesting
that PREPARE may increase planning documentation with minimal health care system
resources. Trial Registration: clinicaltrials.gov Identifier: NCT01550731.
PMID- 28520840
TI - Assessment of nivolumab benefit-risk profile of a 240-mg flat dose relative to a
3-mg/kg dosing regimen in patients with advanced tumors.
AB - Background: Nivolumab 3 mg/kg every 2 weeks (Q2W) has shown benefit versus the
standard of care in melanoma, non-small cell lung cancer (NSCLC), and renal cell
carcinoma (RCC). However, flat dosing is expected to shorten preparation time and
improve ease of administration. With knowledge of nivolumab safety, efficacy, and
pharmacokinetics across a wide dose range in body weight (BW) dosing, assessment
of the benefit-risk profile of a 240-mg flat dose relative to the approved 3
mg/kg dose was approached by quantitative clinical pharmacology. Patients and
methods: A flat dose of 240 mg was selected based on its equivalence to the 3
mg/kg dose at the median BW of ~80 kg in patients in the nivolumab program. The
benefit-risk profile of nivolumab 240 mg was evaluated by comparing exposures at
3 mg/kg Q2W and 240 mg Q2W across BW and tumor types; clinical safety at 3 mg/kg
Q2W by BW and exposure quartiles in melanoma, NSCLC, and RCC; and safety and
efficacy at 240 mg Q2W relative to 3 mg/kg Q2W in melanoma, NSCLC, and RCC.
Results: The median nivolumab exposure and its distribution at 240 mg Q2W were
similar to 3 mg/kg Q2W in the simulated population. Safety analyses did not
demonstrate a clinically meaningful relationship between BW or nivolumab exposure
quartiles and frequency or severity of adverse events. The predicted safety and
efficacy were similar across nivolumab exposure ranges achieved with 3 mg/kg Q2W
or 240 mg Q2W flat dose. Conclusion: Based on population pharmacokinetic
modeling, established flat exposure-response relationships for efficacy and
safety, and clinical safety, the benefit-risk profile of nivolumab 240 mg Q2W was
comparable to 3 mg/kg Q2W. The quantitative clinical pharmacology approach
provided evidence for regulatory decision-making on dose modification, obviating
the need for an independent clinical study.
PMID- 28520841
TI - Chronic Inflammatory Pain Impairs mGluR5-Mediated Depolarization-Induced
Suppression of Excitation in the Anterior Cingulate Cortex.
AB - The anterior cingulate cortex (ACC) is a critical hub for nociceptive perception
and pain-related anxiety. Long-term synaptic plasticity in ACC was found to be
important for chronic inflammatory pain and pain-related anxiety. As short-term
synaptic plasticity, depolarization-induced suppression of excitation (DSE) is
involved in several conditions, such as chronic stress, epilepsy, and autism.
However, it is still unknown whether DSE in the ACC is involved in the central
sensitization of pain and anxiety. Using a whole-cell patch clamp, calcium
imaging, western blot, and behavioral testing, we found that DSE was induced by a
2 s depolarization in postsynaptic pyramidal cells in ACC. DSE was mediated by
endocannabinoid signaling and modulated by metabotropic glutamate receptor 5
(mGluR5). DSE was impaired by decreasing expression and dysfunction of mGluR5 in
a mouse model of inflammatory pain induced by complete Freund's adjuvant. CDPPB,
an mGluR5-positive allosteric modulator, could rescue hypersensitivity and
anxiety-like behavior in this pain model. Our results demonstrated that mGluR5
mediated short-term plasticity in ACC may be a critical mechanism for chronic
pain, and mGluR5 may potentially serve as a target of pain therapy, including
treatments for hyperalgesia and anxiety.
PMID- 28520842
TI - Alcohol Consumption and Breast Cancer Risk in Younger Women According to Family
History of Breast Cancer and Folate Intake.
AB - To evaluate the association between alcohol consumption and breast cancer risk in
younger women, overall and by family history of breast cancer and folate intake,
we prospectively followed 93,835 US women aged 27-44 years in Nurses' Health
Study II who had alcohol consumption data in 1991. Alcohol consumption and folate
intake were measured by food frequency questionnaire every 4 years. We documented
2,866 incident cases of invasive breast cancer between 1991 and 2011. Alcohol
consumption was not associated with breast cancer risk overall (for intake of
>=10 g/day vs. nondrinking, multivariate hazard ratio = 1.07, 95% confidence
interval: 0.94, 1.22). When the association was stratified by family history and
folate intake, a positive association between alcohol consumption and breast
cancer was found among women with a family history and folate intake less than
400 MUg/day (multivariate hazard ratio = 1.82, 95% confidence interval: 1.06,
3.12; P-trend = 0.08). Alcohol consumption was not associated with breast cancer
in other categories of family history and folate intake (P-interaction = 0.55).
In conclusion, in this population of younger women, higher alcohol consumption
was associated with increased risk of breast cancer among those with both a
family history of breast cancer and lower folate intake.
PMID- 28520844
TI - Fracture Risk Assessment With FRAX Using Real-World Data in a Population-Based
Cohort From Israel.
AB - The predictive value of the World Health Organization's Fracture Risk Assessment
Tool (FRAX) was evaluated using real-world community data. A population-based
cohort of 141,320 women aged 50-90 years (median age, 58 years; interquartile
range, 54-67) in 2004 was extracted from the central database of a large Israeli
health-care services provider and insurer. Retrospective FRAX scores were
calculated using computerized health records and compared with actual incidence
of major osteoporotic fractures (MOFs) during the following 10 years. Fracture
proportions of 6.9% for MOFs and 2.2% for hip fractures were expected, as opposed
to 13.5% and 2.9% observed. The area under the receiver operating characteristic
curve (AUC) of FRAX scores calculated without the inclusion of bone mineral
density (BMD) data was 0.65 (95% confidence interval: 0.65, 0.66) for MOF and
0.82 (95% confidence interval: 0.81, 0.82) for hip fracture. A total of 16,578
subjects had BMD data at the index date, and their risk estimates based solely on
BMD exhibited lower predictive performance for both MOFs (AUC = 0.62 vs. 0.65; P
= 0.003) and hip fractures (AUC = 0.78 vs. 0.84; P < 0.001) as compared with
FRAX. FRAX scores based on electronic health records provided reasonable
discrimination despite some underestimation of the absolute risk of nonhip
fractures. Integration of FRAX with routine clinical systems could increase
implementation in daily practice and improve risk detection, especially for
patients without BMD data.
PMID- 28520843
TI - Measurement of Aortic Pulse Wave Velocity With a Connected Bathroom Scale.
AB - BACKGROUND: Measurement of arterial stiffness should be more available. Our aim
was to show that aortic pulse wave velocity can be reliably measured with a
bathroom scale combining the principles of ballistocardiography (BCG) and
impedance plethysmography on a single foot. METHOD: The calibration of the
bathroom scale was conducted on a group of 106 individuals. The aortic pulse wave
velocity was measured with the SphygmoCor in the supine position. Three
consecutive measurements were then performed on the Withings scale in the
standing position. This aorta-leg pulse transit time (alPTT) was then converted
into a velocity with the additional input of the height of the person. Agreement
between the SphygmoCor and the bathroom scale so calibrated is assessed on a
separate group of 86 individuals, following the same protocol. RESULTS: The bias
is 0.25 m.s-1 and the SE 1.39 m.s-1. This agreement with Sphygmocor is
"acceptable" according to the ARTERY classification. The alPTT correlated well
with cfPTT with (Spearman) R = 0.73 in pooled population (cal 0.79, val 0.66).
The aorta-leg pulse wave velocity correlated with carotid-femoral pulse wave
velocity with R = 0.76 (cal 0.80, val 0.70). CONCLUSION: Estimation of the aortic
pulse wave velocity is feasible with a bathroom scale. Further investigations are
needed to improve the repeatability of measurements and to test their accuracy in
different populations and conditions.
PMID- 28520845
TI - Follow-up of a Large Prospective Cohort in the United States Using Linkage With
Multiple State Cancer Registries.
AB - All states in the United States now have a well-established cancer registry.
Linkage with these registries may be a cost-effective method of follow-up for
cancer incidence in multistate cohort studies. However, the sensitivity of
linkage with the current network of state registries for detecting incident
cancer diagnoses within cohort studies is not well-documented. We examined the
sensitivity of registry linkage among 39,368 men and women from 23 states who
enrolled in the Cancer Prevention Study-3 cohort during 2006-2009 and had the
opportunity to self-report cancer diagnoses on a questionnaire in 2011. All
participants provided name and birthdate, and 94% provided a complete social
security number. Of 378 cancer diagnoses between enrollment and 2010 identified
through self-report and verified with medical records, 338 were also detected by
linkage with the 23 state cancer registries (sensitivity of 89%, 95% confidence
interval (CI): 86, 92). Sensitivity was lower for hematologic cancers (69%, 95%
CI: 41, 89) and melanoma (70%, 95% CI: 57, 81). After excluding hematologic
cancers and melanoma, sensitivity was 94% (95% CI: 91, 97). Our results indicate
that linkage with multiple cancer registries can be a sensitive method for
ascertaining incident cancers, other than hematologic cancers and melanoma, in
multistate cohort studies.
PMID- 28520846
TI - Patient-Specific Augmentation Rhinoplasty Using a Three-Dimensional Simulation
Program and Three-Dimensional Printing.
AB - Background: The convergence of three-dimensional (3D) simulation, tissue
engineering, and 3D printing technology is creating a paradigm shift in plastic
surgery. In augmentation rhinoplasty, determining the ideal material and design
method has been a critical issue for many years. Thus, these technologies are
expected to make important contributions to augmentation rhinoplasty. Objectives:
We sought to validate the feasibility of the 3D carving simulation and patient
specific implant fabrication system (3D carving system) in a clinical trial using
reproducibility tests. Methods: Patient-specific implants were designed using a
program developed in-house with preoperative computed tomography (CT). Negative
molds of the implant were fabricated by a 3D printer and silicone was injected
into these molds. Ten actual silicone implants were fabricated and compared with
virtually designed implants. Seven patients underwent surgery and postoperative
CT to confirm implant positioning. Results: Virtually designed implants were
produced into actual implants within 0.07 mm with a 0.17% +/- 0.11% difference.
The percentage within the gap was the highest at the cephalic end of the implant
and reduced from the cephalic to caudal end (most cephalic point: 100%; rightmost
and leftmost point of the implant at the caudal end of the nasal bone: 57.1% and
71.4%, respectively; rightmost and leftmost point at the supratip break: 28.6%
and 28.6%, respectively; and most caudal point: 0%). Conclusions: The 3D carving
system can facilitate rhinoplasty by enabling the more intuitive, rapid, and
accurate fabrication of implants irrespective of surgeon experience level. Level
of Evidence: 4.
PMID- 28520848
TI - Pattern fusion analysis by adaptive alignment of multiple heterogeneous omics
data.
AB - Motivation: Integrating different omics profiles is a challenging task, which
provides a comprehensive way to understand complex diseases in a multi-view
manner. One key for such an integration is to extract intrinsic patterns in
concordance with data structures, so as to discover consistent information across
various data types even with noise pollution. Thus, we proposed a novel framework
called 'pattern fusion analysis' (PFA), which performs automated information
alignment and bias correction, to fuse local sample-patterns (e.g. from each data
type) into a global sample-pattern corresponding to phenotypes (e.g. across most
data types). In particular, PFA can identify significant sample-patterns from
different omics profiles by optimally adjusting the effects of each data type to
the patterns, thereby alleviating the problems to process different platforms and
different reliability levels of heterogeneous data. Results: To validate the
effectiveness of our method, we first tested PFA on various synthetic datasets,
and found that PFA can not only capture the intrinsic sample clustering
structures from the multi-omics data in contrast to the state-of-the-art methods,
such as iClusterPlus, SNF and moCluster, but also provide an automatic weight
scheme to measure the corresponding contributions by data types or even samples.
In addition, the computational results show that PFA can reveal shared and
complementary sample-patterns across data types with distinct signal-to-noise
ratios in Cancer Cell Line Encyclopedia (CCLE) datasets, and outperforms over
other works at identifying clinically distinct cancer subtypes in The Cancer
Genome Atlas (TCGA) datasets. Availability and implementation: PFA has been
implemented as a Matlab package, which is available at
http://www.sysbio.ac.cn/cb/chenlab/images/PFApackage_0.1.rar . Contact:
lnchen@sibs.ac.cn , liujuan@whu.edu.cn or zengtao@sibs.ac.cn. Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 28520847
TI - Maternal Exposure to Nitrogen Dioxide, Intake of Methyl Nutrients, and Congenital
Heart Defects in Offspring.
AB - Nutrients that regulate methylation processes may modify susceptibility to the
effects of air pollutants. Data from the National Birth Defects Prevention Study
(United States, 1997-2006) were used to estimate associations between maternal
exposure to nitrogen dioxide (NO2), dietary intake of methyl nutrients, and the
odds of congenital heart defects in offspring. NO2 concentrations, a marker of
traffic-related air pollution, averaged across postconception weeks 2-8, were
assigned to 6,160 nondiabetic mothers of cases and controls using inverse
distance-squared weighting of air monitors within 50 km of maternal residences.
Intakes of choline, folate, methionine, and vitamins B6 and B12 were assessed
using a food frequency questionnaire. Hierarchical regression models, which
accounted for similarities across defects, were constructed, and relative excess
risks due to interaction were calculated. Relative to women with the lowest NO2
exposure and high methionine intake, women with the highest NO2 exposure and
lowest methionine intake had the greatest odds of offspring with a perimembranous
ventricular septal defect (odds ratio = 3.23, 95% confidence interval: 1.74,
6.01; relative excess risk due to interaction = 2.15, 95% confidence interval:
0.39, 3.92). Considerable departure from additivity was not observed for other
defects. These results provide modest evidence of interaction between nutrition
and NO2 exposure during pregnancy.
PMID- 28520849
TI - Beta blockers and improved progression-free survival in patients with advanced
HER2 negative breast cancer: a retrospective analysis of the ROSE/TRIO-012 study.
AB - Background: Recent retrospective studies suggest that beta-adrenergic blocking
drugs (BB) are associated with improved outcomes in patients with a range of
cancers. Although limited and discordant data suggest that BB may increase
overall survival (OS) in localized breast cancer (BC), there is no information on
the effects of BB in women with advanced BC. Patients and methods: To explore the
association between BB use and BC outcomes, we retrospectively reviewed ROSE/TRIO
012, a double-blinded, multinational phase III trial that randomized 1144
patients with HER2-negative advanced BC to first-line docetaxel in combination
with ramucirumab or placebo. We compared progression-free survival (PFS), OS,
overall response rate, and clinical benefit rate in patients who received BB to
those who did not. Results: 153/1144 (13%) patients received BB; 62% prior to
enrolment and 38% began after enrolment. Median PFS in BB treated patients was
longer than in patients who did not receive them (10.3 versus 8.3 months; HR
0.81; 95% CI 0.66-0.99; P = 0.038). Patients treated with BB only after enrolment
had even higher median PFS (15.5 versus 8.3 months, P < 0.001). In the TNBC
subset, median PFS was 13.0 months with BB, compared to 5.2 months without BB (HR
0.52; 95% CI 0.34-0.79; P = 0.002). The benefit of BB intake in PFS was
independent of treatment-emergent hypertension (P = 0.476) but associated with
treatment arm (P = 0.037). The test for interactions between BB and treatment arm
was not significant (P = 0.276). No differences were seen in OS, overall response
rate, or clinical benefit rate. A validation dataset analysis had consistent but
less substantial improved outcomes for women with node positive operable breast
cancer receiving BB in the BCIRG-005 trial. Conclusions: In this exploratory
analysis, BB intake was associated with significant improvement in PFS,
particularly in patients with TNBC and patients not previously exposed to BB.
Clinical trial number: NCT00703326.
PMID- 28520850
TI - Anatomical Study of Temporal Fat Compartments and its Clinical Application for
Temporal Fat Grafting.
AB - Background: Low satisfaction rates and severe complications are two major
limitations for temporal hollowing augmentation using autologous fat grafting.
Despite fat compartments in temporal region have been reported, its clinical
applied anatomy for fat grafting have not been the subject of studies that show
its benefits objectively and statistically. Objectives: To investigate temporal
fat compartments and relative neurovascular structures in cadavers, developing a
safe and effective fat grafting technique for temporal hollowing augmentation.
Methods: The study was conducted on 8 cadavers (16 temples). The tissue layers,
fat compartments, ligaments, and neurovascular structures in the temporal region
were analysed. The variables were the number and location of sentinel veins,
perforator vessels of the middle temporal vein. Measurements were taken with a
digital calliper. Results: Two separate fat compartments, the lateral temporal
cheek fat compartment and lateral orbital fat compartment, were found in the
subcutaneous layer, and two separate septum compartments, the upper and lower
temporal compartment, were found in the loose areolar tissue layer. One sentinel
vein and 1 to 6 perforator vessels were found to travel through the subcutaneous
tissue layer, traverse the overlapping tissue layers in the lower temporal septum
region, and finally join in the middle temporal vein. Conclusions: The four fat
compartments in the temporal region are ideal receipt sites for fat grafting. The
medial border of the junction of the hairline and temporal line is a safe and
effective cannula entry site for temporal fat grafting. The anterior half of the
lower temporal compartment is a "zone of caution" for temporal fat grafting.
PMID- 28520851
TI - Infectivity of Post-Kala-azar Dermal Leishmaniasis Patients to Sand Flies:
Revisiting a Proof of Concept in the Context of the Kala-azar Elimination Program
in the Indian Subcontinent.
AB - We compared xenodiagnosis with quantitative polymerase chain reaction in skin
biopsies from 3 patients with maculopapular or nodular post-kala-azar dermal
leishmaniasis (PKDL). All patients infected sand flies. Parasite loads in skin
varied from 1428 to 63 058 parasites per microgram. PKDL detection and treatment
are important missing components of the kala-azar elimination program.
PMID- 28520852
TI - Termination mode of a broad QRS complex tachycardia: is the surface
electrocardiogram the key?